{"id": "PMID:183655", "title": "Endothelial contractility - an undecided problem in vascular research.", "content": "The rather old conception that endothelial cells possess an autonomous contractile capability has been reevaluated by several suthors during the past ten years on the basis of three different arguments of various validity: (1) After the topical application of inflammatory mediators tmajno et al. regularly found the endothelial nuclei furnished with numerous identations together with many interendothelial \"gaps\"; Both findings are assumed to be the morphological correlate of an endothelial shortening due to the contraction of the cells. While nuclear indentations seemed to be a rather weak argument to substantiate contractile capabilities, a mechanism other than contraction is outlined for the formation of \"gaps\"; (2) The second argument in favour of endothelial contractility is the occurrence of cytoplasmic filaments that occasionally form cross striated bundles and/or show a \"thick\" and \"thin\" variety. If all these data are assumed to be the morphological evidence for the contractile capability of cells then the conclusion: the more filaments the higher the contractile activity, must be valid. But when compiling those endothelia that are particularly rich in filaments this conclusion does not make sense, because e.g. the endothelium covering the venous valves is crowded with filaments yet an especially high \"contractile activity\" does not seem very probabble. On the other hand, the supposition that endothelial conttractility is entirely independent of the existence of cytoplasmic filaments leaves the question unanswered what then are the filaments for if not serving mechanical purposes. This line of reasoning is supported by both the localization of the filaments predominantly in those endothelia that have to sustain higher degrees of various mechanical stresses and the fact that filamentous structures significatnly increase in number under the influence of hypertension. (3) The final argument brought forward to substantiate endothelial contractility is the demonstration of actin and tropomyosin in the endothelium of various types of blood vessels that also occur under the influence of hypertension; tbut the significance of these findings as a proof for endothelial contractility is curtailed by the fact that the occurrence of actin alone is not conclusive for any contractile capabilities; Furthermore, a convincing demonstration of myosin in endothelial cells is still lacking and the \"thick\" filaments are believed to be noncontractile. Hence we suggest that the endothelial filaments together with the myoid proteins do not serve as a means for \"contractility\" in a true sense but simply act as a design to originate tensile strength.", "contents": "Endothelial contractility - an undecided problem in vascular research. The rather old conception that endothelial cells possess an autonomous contractile capability has been reevaluated by several suthors during the past ten years on the basis of three different arguments of various validity: (1) After the topical application of inflammatory mediators tmajno et al. regularly found the endothelial nuclei furnished with numerous identations together with many interendothelial \"gaps\"; Both findings are assumed to be the morphological correlate of an endothelial shortening due to the contraction of the cells. While nuclear indentations seemed to be a rather weak argument to substantiate contractile capabilities, a mechanism other than contraction is outlined for the formation of \"gaps\"; (2) The second argument in favour of endothelial contractility is the occurrence of cytoplasmic filaments that occasionally form cross striated bundles and/or show a \"thick\" and \"thin\" variety. If all these data are assumed to be the morphological evidence for the contractile capability of cells then the conclusion: the more filaments the higher the contractile activity, must be valid. But when compiling those endothelia that are particularly rich in filaments this conclusion does not make sense, because e.g. the endothelium covering the venous valves is crowded with filaments yet an especially high \"contractile activity\" does not seem very probabble. On the other hand, the supposition that endothelial conttractility is entirely independent of the existence of cytoplasmic filaments leaves the question unanswered what then are the filaments for if not serving mechanical purposes. This line of reasoning is supported by both the localization of the filaments predominantly in those endothelia that have to sustain higher degrees of various mechanical stresses and the fact that filamentous structures significatnly increase in number under the influence of hypertension. (3) The final argument brought forward to substantiate endothelial contractility is the demonstration of actin and tropomyosin in the endothelium of various types of blood vessels that also occur under the influence of hypertension; tbut the significance of these findings as a proof for endothelial contractility is curtailed by the fact that the occurrence of actin alone is not conclusive for any contractile capabilities; Furthermore, a convincing demonstration of myosin in endothelial cells is still lacking and the \"thick\" filaments are believed to be noncontractile. Hence we suggest that the endothelial filaments together with the myoid proteins do not serve as a means for \"contractility\" in a true sense but simply act as a design to originate tensile strength."}
{"id": "PMID:183656", "title": "[Early lesions of the human kidney in paraproteinemie an electron microscopic study (author's transl)].", "content": "In paraproteinemia, especially in multiple myeloma, the origin and morphology of lesions in the kidneys still remain controversial. In many studies mostly of tissue obtained post mortem and examined with light microscopy, a discrepancy between impairment of renal function and minimal pathomorphological findings is often striking. The few studies done with the electron microscope up to now present a wide variety of morphological findings probably due to the different stages of kidney lesions examined, generally in patients with renal insufficiency and nephrotic syndrome. We have therefore tested the question whether early lesions are detectable in the nephron of patients with paraproteinemia who do not show any impairment of renal function. Kidney biopsies were obtained from 8 patients with an average age of 58 years. 6 had multiple myeloma (3 IgG-, I IgA-, 2 Bence-Jones plasmacytoma), 1 Waldenstr\u00f6m's disease and 1 an idiopathic paraproteinemia. Confirmation of the diagnoses was obtained by immunoelectrophoresis, bone marrow biopsy, and sternal puncture. In all cases creatinine clearance was normal and proteinuria was not increased substantially even in patients with a slight Bence-Jones-proteinuria. For electron microscopy small pieces from the renal biopsies were fixed in aldehydes followed by osmium tetroxide and embedded in Epon. The thin sections were stained with uranyl acetate followed by lead citrate...", "contents": "[Early lesions of the human kidney in paraproteinemie an electron microscopic study (author's transl)]. In paraproteinemia, especially in multiple myeloma, the origin and morphology of lesions in the kidneys still remain controversial. In many studies mostly of tissue obtained post mortem and examined with light microscopy, a discrepancy between impairment of renal function and minimal pathomorphological findings is often striking. The few studies done with the electron microscope up to now present a wide variety of morphological findings probably due to the different stages of kidney lesions examined, generally in patients with renal insufficiency and nephrotic syndrome. We have therefore tested the question whether early lesions are detectable in the nephron of patients with paraproteinemia who do not show any impairment of renal function. Kidney biopsies were obtained from 8 patients with an average age of 58 years. 6 had multiple myeloma (3 IgG-, I IgA-, 2 Bence-Jones plasmacytoma), 1 Waldenstr\u00f6m's disease and 1 an idiopathic paraproteinemia. Confirmation of the diagnoses was obtained by immunoelectrophoresis, bone marrow biopsy, and sternal puncture. In all cases creatinine clearance was normal and proteinuria was not increased substantially even in patients with a slight Bence-Jones-proteinuria. For electron microscopy small pieces from the renal biopsies were fixed in aldehydes followed by osmium tetroxide and embedded in Epon. The thin sections were stained with uranyl acetate followed by lead citrate..."}
{"id": "PMID:183657", "title": "[Definition and differential diagnosis of chromophobe pituitary adenomas: light and electron microscopic studies].", "content": "Chromophobe adenomas have been defined by the absence of secretory granules in them. But this definition has become doubtful since a granulation could be electron microscopically demonstrated. Hence we studied a collection of more than 100 surgically removed pituitary adenomas in order to find precise morphological criteria for the differential diagnosis of chromophobe adenomas, specially from the sparsely granulated chromophilic tumors. Furthermore we tried to find relations between the amount and type of granulation of the tumor cells and the clinical endocrine hyperfunction. 108 unselected pituitary tumors were studied by light and electron microscopic methods. For histology the tissue was fixed in Helly's fluid or in buffered formalin. The paraffin wax sections were stained with haematoxylin-eosin, PAS, gallocyanin-chrome alum, carmoisine L-orange G-wool green, Herlant's tetrachrome method, and performic acid-alcian blue-PAS-orange G. For electron microscopy small pieces of the tumor were fixed in buffered glutaraldehyde, postfixed in osmium tetroxide, and embedded in epon 812. Sections were stained with toluidine blue for light microscopy. Thin sections were stained with uranyl acetate and lead citrate. Electron microscopical pictures with a primary magnification of 4000 were semi-quantitatively judged for the content and the extent of rough endoplasmic reticulum, Golgi complexes, secretory granules, lysosomes, and mitochondria by a grading with 6 degrees. Results. With special stains and the electron microscope 46 adenomas could be identified which consisted only of slightly granulated or agranular cells but not of densely granulated cells. These were defined as chromophobe adenomas. Oncocytic adenomas were regarded as another tumor type and were not included. One half of the chromophobe adenomas showed ultrastructurally well developed protein-synthesizing organellas. The diameter of the secretory granules amounts up to 500 mum. One quarter had many autolysosomes or lipid droplets. On the other hand, 18 adenomas of our collection exhibited moderate acidophilic granulation with only a few denser or fully granulated cells. These were designated as sparsely granulated acidophilic adenomas. They were rich in organelles. 89% of them showed a well developed rough endoplasmic reticulum and large Golgi complexes as signs of high endocrine activity. The secretory granules had diameters between 200 and 600 upsilonm. The autolysosomes were for the most part small and rare. The 20 fully granulated acidophilic adenomas could be easily recognized and are not discussed in this paper. The sparsely granulated mucoid cell-adenomas were easily identified by a positive PAS-reaction. From our studies we conclude that chromophobe adenomas exhibit only sparse granulation and no denser or fully granulated tumor cell...", "contents": "[Definition and differential diagnosis of chromophobe pituitary adenomas: light and electron microscopic studies]. Chromophobe adenomas have been defined by the absence of secretory granules in them. But this definition has become doubtful since a granulation could be electron microscopically demonstrated. Hence we studied a collection of more than 100 surgically removed pituitary adenomas in order to find precise morphological criteria for the differential diagnosis of chromophobe adenomas, specially from the sparsely granulated chromophilic tumors. Furthermore we tried to find relations between the amount and type of granulation of the tumor cells and the clinical endocrine hyperfunction. 108 unselected pituitary tumors were studied by light and electron microscopic methods. For histology the tissue was fixed in Helly's fluid or in buffered formalin. The paraffin wax sections were stained with haematoxylin-eosin, PAS, gallocyanin-chrome alum, carmoisine L-orange G-wool green, Herlant's tetrachrome method, and performic acid-alcian blue-PAS-orange G. For electron microscopy small pieces of the tumor were fixed in buffered glutaraldehyde, postfixed in osmium tetroxide, and embedded in epon 812. Sections were stained with toluidine blue for light microscopy. Thin sections were stained with uranyl acetate and lead citrate. Electron microscopical pictures with a primary magnification of 4000 were semi-quantitatively judged for the content and the extent of rough endoplasmic reticulum, Golgi complexes, secretory granules, lysosomes, and mitochondria by a grading with 6 degrees. Results. With special stains and the electron microscope 46 adenomas could be identified which consisted only of slightly granulated or agranular cells but not of densely granulated cells. These were defined as chromophobe adenomas. Oncocytic adenomas were regarded as another tumor type and were not included. One half of the chromophobe adenomas showed ultrastructurally well developed protein-synthesizing organellas. The diameter of the secretory granules amounts up to 500 mum. One quarter had many autolysosomes or lipid droplets. On the other hand, 18 adenomas of our collection exhibited moderate acidophilic granulation with only a few denser or fully granulated cells. These were designated as sparsely granulated acidophilic adenomas. They were rich in organelles. 89% of them showed a well developed rough endoplasmic reticulum and large Golgi complexes as signs of high endocrine activity. The secretory granules had diameters between 200 and 600 upsilonm. The autolysosomes were for the most part small and rare. The 20 fully granulated acidophilic adenomas could be easily recognized and are not discussed in this paper. The sparsely granulated mucoid cell-adenomas were easily identified by a positive PAS-reaction. From our studies we conclude that chromophobe adenomas exhibit only sparse granulation and no denser or fully granulated tumor cell..."}
{"id": "PMID:183738", "title": "Immunogenetic study on the polymorphism of serum alpha2-lipoproteins in mink. I. Identification and genetic control of five Lpm allotypes.", "content": "Five allotypes, Lpm 1, Lpm 2, Lpm 3, Lpm 4, and Lpm 5, were detected by isoimmunization in mink sera. Immunoelectrophoresis, preparative ultracentrifugation, and histochemical tests for lipids and esterase permitted reference of these alloantigenic markers to a very high density alpha2-lipoprotein. Based on population analysis and breeding tests, five genetic units are postulated: Lpm1, Lpm4, Lpm3,4, Lpm1,2, and Lpm2,4,5. These units determine the polymorphism of the Lpm system and behave as Mendelian alleles.", "contents": "Immunogenetic study on the polymorphism of serum alpha2-lipoproteins in mink. I. Identification and genetic control of five Lpm allotypes. Five allotypes, Lpm 1, Lpm 2, Lpm 3, Lpm 4, and Lpm 5, were detected by isoimmunization in mink sera. Immunoelectrophoresis, preparative ultracentrifugation, and histochemical tests for lipids and esterase permitted reference of these alloantigenic markers to a very high density alpha2-lipoprotein. Based on population analysis and breeding tests, five genetic units are postulated: Lpm1, Lpm4, Lpm3,4, Lpm1,2, and Lpm2,4,5. These units determine the polymorphism of the Lpm system and behave as Mendelian alleles."}
{"id": "PMID:183739", "title": "Adenosine 3':5'-cyclic monophosphate-dependence of protein kinase isoenzymes from mouse liver.", "content": "Conditions influencing the cyclic AMP-dependence of protein kinase (ATP-protein phosphotransferase, EC 2.7.1.37) during the phosphorylation of histone were studied. Protein kinase from mouse liver cytosol and the two isoenzymes [PK (protein kinase) I and PK II] isolated from the cytosol by DEAE-cellulose chromatography were tested. A relation between concentration of enzyme and cyclic AMP-dependence was observed for both isoenzymes. Moderate dilution of isoenzyme PK II decreased the stimulation of the enzyme by cyclic AMP. Isoenzyme PK I could be diluted 200 times more than isoenzyme PK II before the same decrease in cyclic AMP-dependence appeared. Long-term incubation with high concentrations of histone increased the activity in the absence of cyclic AMP relative to the activity in the presence of the nucleotide. This was more pronounced for isoenzyme PK II than for isoenzyme PK I. The cyclic AMP concentration needed to give half-maximal binding of the nucleotide was the same as the cyclic AMP concentration (Ka) at which the protein kinase had 50% of its maximal activity. The close correlation between binding and activation is also found in the presence of KCl, which increased the apparent activation constant (Ka) for cyclic AMP. With increasing [KCl], a progressively higher proportion of the histone phosphorylation observed in cytosol was due to cyclic AMP-independent (casein) kinases, leading to an overestimation of the degree of activation of the cyclic AMP-dependent protein kinases present. The relative contributions of cyclic AMP-dependent and -independent kinases to histone phosphorylation at different ionic strengths was determined by use of heat-stable inhibitor and phospho-cellulose chromatography.", "contents": "Adenosine 3':5'-cyclic monophosphate-dependence of protein kinase isoenzymes from mouse liver. Conditions influencing the cyclic AMP-dependence of protein kinase (ATP-protein phosphotransferase, EC 2.7.1.37) during the phosphorylation of histone were studied. Protein kinase from mouse liver cytosol and the two isoenzymes [PK (protein kinase) I and PK II] isolated from the cytosol by DEAE-cellulose chromatography were tested. A relation between concentration of enzyme and cyclic AMP-dependence was observed for both isoenzymes. Moderate dilution of isoenzyme PK II decreased the stimulation of the enzyme by cyclic AMP. Isoenzyme PK I could be diluted 200 times more than isoenzyme PK II before the same decrease in cyclic AMP-dependence appeared. Long-term incubation with high concentrations of histone increased the activity in the absence of cyclic AMP relative to the activity in the presence of the nucleotide. This was more pronounced for isoenzyme PK II than for isoenzyme PK I. The cyclic AMP concentration needed to give half-maximal binding of the nucleotide was the same as the cyclic AMP concentration (Ka) at which the protein kinase had 50% of its maximal activity. The close correlation between binding and activation is also found in the presence of KCl, which increased the apparent activation constant (Ka) for cyclic AMP. With increasing [KCl], a progressively higher proportion of the histone phosphorylation observed in cytosol was due to cyclic AMP-independent (casein) kinases, leading to an overestimation of the degree of activation of the cyclic AMP-dependent protein kinases present. The relative contributions of cyclic AMP-dependent and -independent kinases to histone phosphorylation at different ionic strengths was determined by use of heat-stable inhibitor and phospho-cellulose chromatography."}
{"id": "PMID:183740", "title": "Kinetics and reaction mechanism of yeast alcohol dehydrogenase with long-chain primary alcohols.", "content": "Kinetic studies of yeast alcohol dehydrogenase with NAD+ and ethanol, hexanol or decanol as substrates invariably result in non-linear Lineweaver-Burk plots if the alcohol is the variable substrate. The kinetic coefficients determined from secondary plots are consistent with an 'equilibrium random-order' mechanism for extremely low alcohol concentrations and for all alcohols, the transformation of the ternary complexes being the rate-limiting step of the reaction. This mechanism also applies to long-chain substrates at high concentrations, whereas the rate of the ethanol-NAD+ reaction at high ethanol concentrations is determined by the dissociation of the enzyme-NADH complex. The dissociation constants for the enzyme-NAD+ complex and for the enzyme-alcohol complexes obtained from the kinetic quotients satisfactorily correspond to the dissociation constants obtained by use of other techniques. It is suggested that the non-linear curves may be attributed to a structural change in the enzyme itself, caused by the alcohol.", "contents": "Kinetics and reaction mechanism of yeast alcohol dehydrogenase with long-chain primary alcohols. Kinetic studies of yeast alcohol dehydrogenase with NAD+ and ethanol, hexanol or decanol as substrates invariably result in non-linear Lineweaver-Burk plots if the alcohol is the variable substrate. The kinetic coefficients determined from secondary plots are consistent with an 'equilibrium random-order' mechanism for extremely low alcohol concentrations and for all alcohols, the transformation of the ternary complexes being the rate-limiting step of the reaction. This mechanism also applies to long-chain substrates at high concentrations, whereas the rate of the ethanol-NAD+ reaction at high ethanol concentrations is determined by the dissociation of the enzyme-NADH complex. The dissociation constants for the enzyme-NAD+ complex and for the enzyme-alcohol complexes obtained from the kinetic quotients satisfactorily correspond to the dissociation constants obtained by use of other techniques. It is suggested that the non-linear curves may be attributed to a structural change in the enzyme itself, caused by the alcohol."}
{"id": "PMID:183741", "title": "Kinetics of reaction of (nitrotyrosyl)cytochrome c with ligands.", "content": "The reaction of [nitrotyrosyl]cytochrome c with ligands was studied by stopped-flow techniques. At pH 7.0 the reaction with imidazole shows two distinct phases, one fast phase being concentration-dependent and a slow phase being concentration-independent. The results are consistent with the existence of two forms of [nitrotyrosyl]cytochrome c in solutions [Schejter et al. (1970) Biochemistry 9, 5118-5122]; form I, the smaller fraction, seems to be responsible for the slow first-order process.", "contents": "Kinetics of reaction of (nitrotyrosyl)cytochrome c with ligands. The reaction of [nitrotyrosyl]cytochrome c with ligands was studied by stopped-flow techniques. At pH 7.0 the reaction with imidazole shows two distinct phases, one fast phase being concentration-dependent and a slow phase being concentration-independent. The results are consistent with the existence of two forms of [nitrotyrosyl]cytochrome c in solutions [Schejter et al. (1970) Biochemistry 9, 5118-5122]; form I, the smaller fraction, seems to be responsible for the slow first-order process."}
{"id": "PMID:183742", "title": "Demonstration of an androgen receptor in rat pancreas.", "content": "[1,2,6,7-3H]Testosterone (250 muCi) was administered to castrated male rats; after 30 min a labelled testosterone-receptor protein complex with a pI of 5.1 was recovered from the pancreatic cytosol. A labelled testosterone-receptor complex with an identical pI was also extracted from the nuclear fraction of rat pancreas after incubation of minced pancreatic tissue with 0.1 muM-]1,2,6,7-3H]testosterone for 30 min at 37 degrees C. Studies in vitro showed that [1,2,6,7-3H]testosterone was bound to a receptor protein focusing at a pI of 5.1 and with a Kd of 2 nM and a number of binding sites of 4.7 fmol/mg of protein in castrated male rats. The testosterone-receptor complex sedimented at 3.5 S in high-salt sucrose-density gradients, was excluded from Sephadex G-200 and Ultragel ACA-34, was stable towards treatment with dextran-coated charcoal, was relatively sensitive to heat, and was stable to treatment with deoxyribonuclease and ribonuclease, but was sensitive to treatment which proteinase. It is suggested that the pancreatic androgen receptor, which was also present in castrated female rats, may play a role in sex-steroid regulation of pancreatic function.", "contents": "Demonstration of an androgen receptor in rat pancreas. [1,2,6,7-3H]Testosterone (250 muCi) was administered to castrated male rats; after 30 min a labelled testosterone-receptor protein complex with a pI of 5.1 was recovered from the pancreatic cytosol. A labelled testosterone-receptor complex with an identical pI was also extracted from the nuclear fraction of rat pancreas after incubation of minced pancreatic tissue with 0.1 muM-]1,2,6,7-3H]testosterone for 30 min at 37 degrees C. Studies in vitro showed that [1,2,6,7-3H]testosterone was bound to a receptor protein focusing at a pI of 5.1 and with a Kd of 2 nM and a number of binding sites of 4.7 fmol/mg of protein in castrated male rats. The testosterone-receptor complex sedimented at 3.5 S in high-salt sucrose-density gradients, was excluded from Sephadex G-200 and Ultragel ACA-34, was stable towards treatment with dextran-coated charcoal, was relatively sensitive to heat, and was stable to treatment with deoxyribonuclease and ribonuclease, but was sensitive to treatment which proteinase. It is suggested that the pancreatic androgen receptor, which was also present in castrated female rats, may play a role in sex-steroid regulation of pancreatic function."}
{"id": "PMID:183743", "title": "Autoxidation of soluble trypsin-cleaved microsomal ferrocytochrome b5 and formation of superoxide radicals.", "content": "The rate and mechanism of autoxidation of soluble ferrocytochrome b5, prepared from liver microsomal suspensions, appear to reflect an intrinsic property of membrane-bound cytochrome b5. The first-order rate constant for autoxidation of trypsin-cleaved ferrocytochrome b5, prepared by reduction with dithionite, was 2.00 X 10(-3) +/- 0.19 X 10(-3) S-1 (mean +/- S.E.M., n =8) when measured at 30 degrees C in 10 mM-phosphate buffer, pH 7.4. At 37 degrees C in aerated 10 mM-phosphate buffer (pH 7.4)/0.15 M-KCl, the rate constant was 5.6 X 10(-3) S-1. The autoxidation reaction was faster at lower pH values and at high ionic strengths. Unlike ferromyoglobin, the autoxidation reaction of which is maximal at low O2 concentrations, autoxidation of ferrocytochrome b5 showed a simple O2-dependence with an apparent Km for O2 of 2.28 X 10(-4) M (approx. 20kPa or 150mmHg)9 During autoxidation, 0.25 mol of O2 was consumed per mol of cytochrome oxidized. Cyanide, nucleophilic anions, EDTA and catalase each had little or no effect on autoxidation rates. Adrenaline significantly enhanced autoxidation rates, causing a tenfold increase at 0.6 mM. Ferrocytochrome b5 reduced an excess of cytochrome c in a biphasic manner. An initial rapid phase, independent of O2 concentration, was unaffected by superoxide dismutase. A subsequent slower phase, which continued for up to 60 min, was retarded at low O2 concentrations and inhibited by 65% by superoxide dismutase at a concentration of 3 mug/ml. It is concluded that autoxidation is responsible for a significant proportion of electron flow between cytochrome b5 and O2 in liver endoplasmic membranes, this reaction being capable of generating superoxide anions. A biological role for the reaction is discussed.", "contents": "Autoxidation of soluble trypsin-cleaved microsomal ferrocytochrome b5 and formation of superoxide radicals. The rate and mechanism of autoxidation of soluble ferrocytochrome b5, prepared from liver microsomal suspensions, appear to reflect an intrinsic property of membrane-bound cytochrome b5. The first-order rate constant for autoxidation of trypsin-cleaved ferrocytochrome b5, prepared by reduction with dithionite, was 2.00 X 10(-3) +/- 0.19 X 10(-3) S-1 (mean +/- S.E.M., n =8) when measured at 30 degrees C in 10 mM-phosphate buffer, pH 7.4. At 37 degrees C in aerated 10 mM-phosphate buffer (pH 7.4)/0.15 M-KCl, the rate constant was 5.6 X 10(-3) S-1. The autoxidation reaction was faster at lower pH values and at high ionic strengths. Unlike ferromyoglobin, the autoxidation reaction of which is maximal at low O2 concentrations, autoxidation of ferrocytochrome b5 showed a simple O2-dependence with an apparent Km for O2 of 2.28 X 10(-4) M (approx. 20kPa or 150mmHg)9 During autoxidation, 0.25 mol of O2 was consumed per mol of cytochrome oxidized. Cyanide, nucleophilic anions, EDTA and catalase each had little or no effect on autoxidation rates. Adrenaline significantly enhanced autoxidation rates, causing a tenfold increase at 0.6 mM. Ferrocytochrome b5 reduced an excess of cytochrome c in a biphasic manner. An initial rapid phase, independent of O2 concentration, was unaffected by superoxide dismutase. A subsequent slower phase, which continued for up to 60 min, was retarded at low O2 concentrations and inhibited by 65% by superoxide dismutase at a concentration of 3 mug/ml. It is concluded that autoxidation is responsible for a significant proportion of electron flow between cytochrome b5 and O2 in liver endoplasmic membranes, this reaction being capable of generating superoxide anions. A biological role for the reaction is discussed."}
{"id": "PMID:183744", "title": "An investigation of the nicotinamide-adenine dinucleotide-induced 'tightening' of the structure of glyceraldehyde 3-phosphate dehydrogenase.", "content": "An investigation was made of the effect of NAD+ analogues on subunit interactions in yeast and rabbit muscle glyceraldehyde 3-phosphate dehydrogenases by using the subunit exchange (hybridization) method described previously [e.g. see Osborne & Hollaway (1975) Biochem. J. 151, 37-45]. The ligands ATP, ITP, ADP, AMP, cyclic AMP and ADP-ribose like NADH, all caused an apparent weakening of intramolecular subunit interactions, whereas NAD+ caused an apparent increase in the stability of the tetrameric enzyme molecules. A mixture of NMN and AMP, although it did not simulate completely the NAD+-induced 'tightening' of the enzyme structure, did result in a more than 20-fold decrease in the rate of subunit exchange compared with that in the presence of AMP alone. These results show that occupancy of the NMN subsite of the enzyme NAD+-binding site is insufficient in itself to give the marked tightening of the enzyme structure induced by NAD+. The 'tightening' effect is specific in that it seems to require a phosphodiester link between NMN and ADP-ribose. These effects are discussed in terms of the detailed X-ray structure of the lobster holoenzyme [Buehner et al. (1974) J. Mol. Biol. 90, 25-49].", "contents": "An investigation of the nicotinamide-adenine dinucleotide-induced 'tightening' of the structure of glyceraldehyde 3-phosphate dehydrogenase. An investigation was made of the effect of NAD+ analogues on subunit interactions in yeast and rabbit muscle glyceraldehyde 3-phosphate dehydrogenases by using the subunit exchange (hybridization) method described previously [e.g. see Osborne & Hollaway (1975) Biochem. J. 151, 37-45]. The ligands ATP, ITP, ADP, AMP, cyclic AMP and ADP-ribose like NADH, all caused an apparent weakening of intramolecular subunit interactions, whereas NAD+ caused an apparent increase in the stability of the tetrameric enzyme molecules. A mixture of NMN and AMP, although it did not simulate completely the NAD+-induced 'tightening' of the enzyme structure, did result in a more than 20-fold decrease in the rate of subunit exchange compared with that in the presence of AMP alone. These results show that occupancy of the NMN subsite of the enzyme NAD+-binding site is insufficient in itself to give the marked tightening of the enzyme structure induced by NAD+. The 'tightening' effect is specific in that it seems to require a phosphodiester link between NMN and ADP-ribose. These effects are discussed in terms of the detailed X-ray structure of the lobster holoenzyme [Buehner et al. (1974) J. Mol. Biol. 90, 25-49]."}
{"id": "PMID:183745", "title": "Kinetic analysis of experiments involving the single turnover of an enzyme.", "content": "The complete solution to the kinetic equation for nucleotide fluorescence quenching on addition of pyruvate to the late dehydrogenase-NADH complex modifies previous interpretations of such experiments.", "contents": "Kinetic analysis of experiments involving the single turnover of an enzyme. The complete solution to the kinetic equation for nucleotide fluorescence quenching on addition of pyruvate to the late dehydrogenase-NADH complex modifies previous interpretations of such experiments."}
{"id": "PMID:183746", "title": "The elementary reactions of the pig heart pyruvate dehydrogenase complex. A study of the inhibition by phosphorylation.", "content": "1. A method was devised for preparing pig heart pyruvate dehydrogenase free of thiamin pyrophosphate (TPP), permitting studies of the binding of [35S]TPP to pyruvate dehydrogenase and pyruvate dehydrogenase phosphate. The Kd of TPP for pyruvate dehydrogenase was in the range 6.2-8.2 muM, whereas that for pyruvate dehydrogenase phosphate was approximately 15 muM; both forms of the complex contained about the same total number of binding sites (500 pmol/unit of enzyme). EDTA completely inhibited binding of TPP; sodium pyrophosphate, adenylyl imidodiphosphate and GTP, which are inhibitors (competitive with TPP) of the overall pyruvate dehydrogenase reaction, did not appreciably affect TPP binding. 2. Initial-velocity patterns of the overall pyruvate dehydrogenase reaction obtained with varying TPP, CoA and NAD+ concentrations at a fixed pyruvate concentration were consistent with a sequential three-site Ping Pong mechanism; in the presence of oxaloacetate and citrate synthase to remove acetyl-CoA (an inhibitor of the overall reaction) the values of Km for NAD+ and CoA were 53+/- 5 muM and 1.9+/-0.2 muM respectively. Initial-velocity patterns observed with varying TPP concentrations at various fixed concentrations of pyruvate were indicative of either a compulsory order of addition of substrates to form a ternary complex (pyruvate-Enz-TPP) or a random-sequence mechanism in which interconversion of ternary intermediates is rate-limiting; values of Km for pyruvate and TPP were 25+/-4 muM and 50+/-10 nM respectively. The Kia-TPP (the dissociation constant for Enz-TPP complex calculated from kinetic plots) was close to the value of Kd-TPP (determined by direct binding studies). 3. Inhibition of the overall pyruvate dehydrogenase reaction by pyrophosphate was mixed non-competitive versus pyruvate and competitive versus TPP; however, pyrophosphate did not alter the calculated value for Kia-TPP, consistent with the lack of effect of pyrophosphate on the Kd for TPP. 4. Pyruvate dehydrogenase catalysed a TPP-dependent production of 14CO2 from [1-14C]pyruvate in the absence of NAD+ and CoA at approximately 0.35% of the overall reaction rate; this was substantially inhibited by phosphorylation of the enzyme both in the presence and absence of acetaldehyde (which stimulates the rate of 14CO2 production two- or three-fold). 5. Pyruvate dehydrogenase catalysed a partial back-reaction in the presence of TPP, acetyl-CoA and NADH. The Km for TPP was 4.1+/-0.5 muM. The partial back-reaction was stimulated by acetaldehyde, inhibited by pyrophosphate and abolished by phosphorylation. 6. Formation of enzyme-bound [14C]acetylhydrolipoate from [3-14C]pyruvate but not from [1-14C]acetyl-CoA was inhibited by phosphorylation. Phosphorylation also substantially inhibited the transfer of [14C]acetyl groups from enzyme-bound [14C]acetylhydrolipoate to TPP in the presence of NADH. 7...", "contents": "The elementary reactions of the pig heart pyruvate dehydrogenase complex. A study of the inhibition by phosphorylation. 1. A method was devised for preparing pig heart pyruvate dehydrogenase free of thiamin pyrophosphate (TPP), permitting studies of the binding of [35S]TPP to pyruvate dehydrogenase and pyruvate dehydrogenase phosphate. The Kd of TPP for pyruvate dehydrogenase was in the range 6.2-8.2 muM, whereas that for pyruvate dehydrogenase phosphate was approximately 15 muM; both forms of the complex contained about the same total number of binding sites (500 pmol/unit of enzyme). EDTA completely inhibited binding of TPP; sodium pyrophosphate, adenylyl imidodiphosphate and GTP, which are inhibitors (competitive with TPP) of the overall pyruvate dehydrogenase reaction, did not appreciably affect TPP binding. 2. Initial-velocity patterns of the overall pyruvate dehydrogenase reaction obtained with varying TPP, CoA and NAD+ concentrations at a fixed pyruvate concentration were consistent with a sequential three-site Ping Pong mechanism; in the presence of oxaloacetate and citrate synthase to remove acetyl-CoA (an inhibitor of the overall reaction) the values of Km for NAD+ and CoA were 53+/- 5 muM and 1.9+/-0.2 muM respectively. Initial-velocity patterns observed with varying TPP concentrations at various fixed concentrations of pyruvate were indicative of either a compulsory order of addition of substrates to form a ternary complex (pyruvate-Enz-TPP) or a random-sequence mechanism in which interconversion of ternary intermediates is rate-limiting; values of Km for pyruvate and TPP were 25+/-4 muM and 50+/-10 nM respectively. The Kia-TPP (the dissociation constant for Enz-TPP complex calculated from kinetic plots) was close to the value of Kd-TPP (determined by direct binding studies). 3. Inhibition of the overall pyruvate dehydrogenase reaction by pyrophosphate was mixed non-competitive versus pyruvate and competitive versus TPP; however, pyrophosphate did not alter the calculated value for Kia-TPP, consistent with the lack of effect of pyrophosphate on the Kd for TPP. 4. Pyruvate dehydrogenase catalysed a TPP-dependent production of 14CO2 from [1-14C]pyruvate in the absence of NAD+ and CoA at approximately 0.35% of the overall reaction rate; this was substantially inhibited by phosphorylation of the enzyme both in the presence and absence of acetaldehyde (which stimulates the rate of 14CO2 production two- or three-fold). 5. Pyruvate dehydrogenase catalysed a partial back-reaction in the presence of TPP, acetyl-CoA and NADH. The Km for TPP was 4.1+/-0.5 muM. The partial back-reaction was stimulated by acetaldehyde, inhibited by pyrophosphate and abolished by phosphorylation. 6. Formation of enzyme-bound [14C]acetylhydrolipoate from [3-14C]pyruvate but not from [1-14C]acetyl-CoA was inhibited by phosphorylation. Phosphorylation also substantially inhibited the transfer of [14C]acetyl groups from enzyme-bound [14C]acetylhydrolipoate to TPP in the presence of NADH. 7..."}
{"id": "PMID:183747", "title": "Electrophoretic analysis of multiple forms of myosin in fast-twitch and slow-twitch muscles of the chick.", "content": "1. A method is described for the electrophoretic analysis of intact myosin in polyacrylamide gel in a buffer system containing 0.02 M-pyrophosphate and 10% (v/v) glycerol, pH 8.8. 2. In this system chicken skeletal-muscle myosins reveal five distinct electrophoretic components, three components from the fast-twitch posterior latissimus dorsi muscle and two slower-migrating components from the slow-twitch anterior latissimus dorsi muscle. 3. The Ca2+-activated ATPase (adenosine triphosphatase) activity of myosin components was measured by densitometric scanning of the gel for the Ca3(PO4)2 precipitate formed during the ATPase reaction and subsequently for stained protein. Each component from the same muscle appears to have identical ATPase activity, but components from the fast-twitch muscle had an activity 2.2 times higher than those from the slow-twitch muscle. 4. On re-electrophoresis in the same buffer system, individual fractions of fast-twitch myosin did not reproduce the three-band pattern of the original myosin, but migrated at rates consistent with their original mobility. 5. Analysis of the mobility of the three fast-twitch myosin components in gels of different concentrations suggests that they are not stable oligomers of each other. 6. It is suggested that these components of fast-twitch myosin and slow-twitch myosin are isoenzymes of myosin.", "contents": "Electrophoretic analysis of multiple forms of myosin in fast-twitch and slow-twitch muscles of the chick. 1. A method is described for the electrophoretic analysis of intact myosin in polyacrylamide gel in a buffer system containing 0.02 M-pyrophosphate and 10% (v/v) glycerol, pH 8.8. 2. In this system chicken skeletal-muscle myosins reveal five distinct electrophoretic components, three components from the fast-twitch posterior latissimus dorsi muscle and two slower-migrating components from the slow-twitch anterior latissimus dorsi muscle. 3. The Ca2+-activated ATPase (adenosine triphosphatase) activity of myosin components was measured by densitometric scanning of the gel for the Ca3(PO4)2 precipitate formed during the ATPase reaction and subsequently for stained protein. Each component from the same muscle appears to have identical ATPase activity, but components from the fast-twitch muscle had an activity 2.2 times higher than those from the slow-twitch muscle. 4. On re-electrophoresis in the same buffer system, individual fractions of fast-twitch myosin did not reproduce the three-band pattern of the original myosin, but migrated at rates consistent with their original mobility. 5. Analysis of the mobility of the three fast-twitch myosin components in gels of different concentrations suggests that they are not stable oligomers of each other. 6. It is suggested that these components of fast-twitch myosin and slow-twitch myosin are isoenzymes of myosin."}
{"id": "PMID:183748", "title": "The identification and properties of phosphatases in skeletal muscle with activity towards the inhibitory subunit of troponin, and their relationship to other phosphoprotein phosphatases.", "content": "1. Phosphoprotein phosphatases with activity towards the inhibitory subunit of troponin (troponin I), phosphorylase a and lysine-rich histone (fraction F1) have been fractionated from rat skeletal muscle by chromatography on Sephadex G-200 and polylysine-Sepharose. Six separate fractions were identified on the basis of substrate specificity and behaviour during chromatography. 2. All fractions showed similar Km values for any given protein substrate. The Km for troponin I (5 muM) was significantly lower than that previously reported. 3. Phosphatase activities towards troponin I and hosphorylase a did not show a requirement for bivalent-metal ions. Two of the fractions with only minor activity towards histone were activated by Mn2+. 4. Discontinuous polyacrylamide-gel-electrophoresis studies indicated that several of the fractions contained more than one phosphatase activity, and additionally showed that several of the activities could exist in different aggregation states. On the basis of these studies at least two phosphatases with activity only towards troponin I were identified. In addition, phosphorylase phosphatase (which has considerable activity towards troponin I) and a general phosphatase with activity towards all three substrates were found. 5. A fraction with mol.wt. of 150000 could be activated by freezing with 2-mercaptoethanol or by heating to 55 degrees C. This activation was accompanied by a decrease in mol.wt. to 25000. 6. The total amount of phosphatase with activity towards troponin I which was extracted would be sufficient to dephosphorylate all the troponin I present in skeletal muscle in approximately 10s.", "contents": "The identification and properties of phosphatases in skeletal muscle with activity towards the inhibitory subunit of troponin, and their relationship to other phosphoprotein phosphatases. 1. Phosphoprotein phosphatases with activity towards the inhibitory subunit of troponin (troponin I), phosphorylase a and lysine-rich histone (fraction F1) have been fractionated from rat skeletal muscle by chromatography on Sephadex G-200 and polylysine-Sepharose. Six separate fractions were identified on the basis of substrate specificity and behaviour during chromatography. 2. All fractions showed similar Km values for any given protein substrate. The Km for troponin I (5 muM) was significantly lower than that previously reported. 3. Phosphatase activities towards troponin I and hosphorylase a did not show a requirement for bivalent-metal ions. Two of the fractions with only minor activity towards histone were activated by Mn2+. 4. Discontinuous polyacrylamide-gel-electrophoresis studies indicated that several of the fractions contained more than one phosphatase activity, and additionally showed that several of the activities could exist in different aggregation states. On the basis of these studies at least two phosphatases with activity only towards troponin I were identified. In addition, phosphorylase phosphatase (which has considerable activity towards troponin I) and a general phosphatase with activity towards all three substrates were found. 5. A fraction with mol.wt. of 150000 could be activated by freezing with 2-mercaptoethanol or by heating to 55 degrees C. This activation was accompanied by a decrease in mol.wt. to 25000. 6. The total amount of phosphatase with activity towards troponin I which was extracted would be sufficient to dephosphorylate all the troponin I present in skeletal muscle in approximately 10s."}
{"id": "PMID:183749", "title": "Investigation of the abnormal low-density lipoproteins occurring in patients with obstructive jaundice.", "content": "The abnormal lipoproteins of the density range 1.019-1.063g/cm3 occurring in the plasma of patients with obstructive jaundice were studied. Subfractionation of this density class by combined sodium phosphotungstate precipitation, ultracentrifugation, and column chromatography on hydroxyapatite and agarose gel yielded essentially three fractions: (1) lipoprotein-X, (2) A triglyceride-rich lipoprotein for which we propose the term lipoprotein-Y and (3) an abnormal lipoprotein, lipoprotein-B. Marked differences between these fractions with respect to electron-microscopic appearance, hydrated densities, chemical composition and immunochemical characteristics were observed. The protein moiety of lipoprotein-X consisted primarily of apolipoprotein-C and albumin. Lipoprotein-Y showed, in addition to apolipoprotein-C, the presence of apolipoprotein-B. The 'lipoprotein-B' fraction isolated from sera of these patients had higher triglyceride and free cholesterol contents than that of normal individuals and an unusually high content of apolipoprotein-C. The relative distribution of lipoprotein-X, lipoprotein-Y and 'lipoprotein-B' varied from patient to patient. The importance of considering the existence of lipoprotein-Y in screening patients for cholestasis by the lipoprotein-X test is discussed.", "contents": "Investigation of the abnormal low-density lipoproteins occurring in patients with obstructive jaundice. The abnormal lipoproteins of the density range 1.019-1.063g/cm3 occurring in the plasma of patients with obstructive jaundice were studied. Subfractionation of this density class by combined sodium phosphotungstate precipitation, ultracentrifugation, and column chromatography on hydroxyapatite and agarose gel yielded essentially three fractions: (1) lipoprotein-X, (2) A triglyceride-rich lipoprotein for which we propose the term lipoprotein-Y and (3) an abnormal lipoprotein, lipoprotein-B. Marked differences between these fractions with respect to electron-microscopic appearance, hydrated densities, chemical composition and immunochemical characteristics were observed. The protein moiety of lipoprotein-X consisted primarily of apolipoprotein-C and albumin. Lipoprotein-Y showed, in addition to apolipoprotein-C, the presence of apolipoprotein-B. The 'lipoprotein-B' fraction isolated from sera of these patients had higher triglyceride and free cholesterol contents than that of normal individuals and an unusually high content of apolipoprotein-C. The relative distribution of lipoprotein-X, lipoprotein-Y and 'lipoprotein-B' varied from patient to patient. The importance of considering the existence of lipoprotein-Y in screening patients for cholestasis by the lipoprotein-X test is discussed."}
{"id": "PMID:183750", "title": "A purification procedure for the soluble cytochrome oxidase and some other respiratory proteins from Pseudomonas aeruginosa.", "content": "The production of the soluble cytochrome oxidase/nitrite reductase in the bacterium Pseudomonas aeruginosa is favoured by anaerobic conditions and the presence of KNO3(20g/l) in the culture medium. Of three methods commonly used for the disruption of bacterial suspensions (ultrasonication, liquid-shear homogenization and glass-bead grinding), sonication proved the most efficient in releasing the Pseudomonas cytochrome oxidase. A polarographic assay of Pseudomonas cytochrome oxidase activity with sodium ascorbate as substrate and NNN'N'-tetramethyl-p-phenylenediamine dihydrochloride as electron mediator is described. A purification procedure was developed which can be used on the small scale (40-litre cultures) or the large scale (400-litre cultures) and provides high yields of three respiratory-chain proteins, Pseudomonas cytochrome oxidase, cytochrome c551 and azurin, in a pure state. A typical preparation of 250g of Ps.aeruginosa cell paste yielded 180mg of Pseudomonas cytochrome oxidase, 81 mg of Pseudomonas cytochrome c551 and 275mg of Pseudomonas azurin.", "contents": "A purification procedure for the soluble cytochrome oxidase and some other respiratory proteins from Pseudomonas aeruginosa. The production of the soluble cytochrome oxidase/nitrite reductase in the bacterium Pseudomonas aeruginosa is favoured by anaerobic conditions and the presence of KNO3(20g/l) in the culture medium. Of three methods commonly used for the disruption of bacterial suspensions (ultrasonication, liquid-shear homogenization and glass-bead grinding), sonication proved the most efficient in releasing the Pseudomonas cytochrome oxidase. A polarographic assay of Pseudomonas cytochrome oxidase activity with sodium ascorbate as substrate and NNN'N'-tetramethyl-p-phenylenediamine dihydrochloride as electron mediator is described. A purification procedure was developed which can be used on the small scale (40-litre cultures) or the large scale (400-litre cultures) and provides high yields of three respiratory-chain proteins, Pseudomonas cytochrome oxidase, cytochrome c551 and azurin, in a pure state. A typical preparation of 250g of Ps.aeruginosa cell paste yielded 180mg of Pseudomonas cytochrome oxidase, 81 mg of Pseudomonas cytochrome c551 and 275mg of Pseudomonas azurin."}
{"id": "PMID:183751", "title": "Some spectral and steady-state kinetic properties of Pseudomonas cytochrome oxidase.", "content": "Some spectra of Pseudomonas cytochrome oxidase are reported, both for comparison with those of other workers and to illustrate the differences between the ascorbate- and dithionite-reduced forms of the enzyme. A spectrum of the reduced enzyme-CO complex, prepared in the absence of added reductants by incubation under CO, is also included. Ultracentrifugation studies yielded a value for the sedimentation coefficient (s20,w) of 7.5S, and an isoelectric point of pH6.9 was determined by isoelectric focusing. Steady-state kinetic constants of the electron donors, quinol, sodium ascorbate, reduced Pseudomonas azurin and Pseudomonas ferrocytochrome c551 were investigated giving Km values of 30mM, 4mM, 49muM and 5.6muM respectively. The two protein substrates were observed to be subject to product inhibition and the Ki for oxidized Pseudomonas azurin was evaluated at 4.9muM. Steady-state kinetics were also used to investigate the effects of the oxidation products of dithionite on the oxidase and nitrite reductase activities of Pseudomonas cytochrome oxidase. These experiments showed that whereas the oxidase activity was inhibited, the nitrite reductase activity was slightly enhanced.", "contents": "Some spectral and steady-state kinetic properties of Pseudomonas cytochrome oxidase. Some spectra of Pseudomonas cytochrome oxidase are reported, both for comparison with those of other workers and to illustrate the differences between the ascorbate- and dithionite-reduced forms of the enzyme. A spectrum of the reduced enzyme-CO complex, prepared in the absence of added reductants by incubation under CO, is also included. Ultracentrifugation studies yielded a value for the sedimentation coefficient (s20,w) of 7.5S, and an isoelectric point of pH6.9 was determined by isoelectric focusing. Steady-state kinetic constants of the electron donors, quinol, sodium ascorbate, reduced Pseudomonas azurin and Pseudomonas ferrocytochrome c551 were investigated giving Km values of 30mM, 4mM, 49muM and 5.6muM respectively. The two protein substrates were observed to be subject to product inhibition and the Ki for oxidized Pseudomonas azurin was evaluated at 4.9muM. Steady-state kinetics were also used to investigate the effects of the oxidation products of dithionite on the oxidase and nitrite reductase activities of Pseudomonas cytochrome oxidase. These experiments showed that whereas the oxidase activity was inhibited, the nitrite reductase activity was slightly enhanced."}
{"id": "PMID:183752", "title": "Oxidation-reduction potentials of molybdenum, flavin and iron-sulphur centres in milk xanthine oxidase.", "content": "1. The mid-point reduction potentials of the various groups in xanthine oxidase from bovine milk were determined by potentiometric titration with dithionite in the presence of dye mediators, removing samples for quantification of the reduced species by e.p.r. (electron-paramagnetic-resonance) spectroscopy. The values obtained for the functional enzyme in pyrophosphate buffer, pH8.2, are: Fe/S centre I, -343 +/- 15mV; Fe/S II, -303 +/- 15mV; FAD/FADH-; -351 +/- 20mV; FADH/FADH2, -236 +/-mV; Mo(VI)/Mo(V) (Rapid), -355 +/- 20mV; Mo(V) (Rapid)/Mo(IV), -355 +/- 20mV. 2. Behaviour of the functional enzyme is essentially ideal in Tris but less so in pyrophosphate. In Tris, the potential for Mo(VI)/Mo(V) (Rapid) is lowered relative to that in pyrophosphate, but the potential for Fe/S II is raised. The influence of buffer on the potentials was investigated by partial-reduction experiments with six other buffers. 3. Conversion of the enzyme with cyanide into the non-functional form, which gives the Slow molybdenum signal, or alkylation of FAD, has little effect on the mid-point potentials of the other centres. The potentials associated with the Slow signal are: Mo(VI)/Mo(V) (Slow), -440 +/- 25mV; Mo(V) (Slow)/Mo(IV), -480 +/- 25 mV. This signal exhibits very sluggish equilibration with the mediator system. 4. The deviations from ideal behaviour are discussed in terms of possible binding of buffer ions or anti-co-operative interactions amongst the redox centres.", "contents": "Oxidation-reduction potentials of molybdenum, flavin and iron-sulphur centres in milk xanthine oxidase. 1. The mid-point reduction potentials of the various groups in xanthine oxidase from bovine milk were determined by potentiometric titration with dithionite in the presence of dye mediators, removing samples for quantification of the reduced species by e.p.r. (electron-paramagnetic-resonance) spectroscopy. The values obtained for the functional enzyme in pyrophosphate buffer, pH8.2, are: Fe/S centre I, -343 +/- 15mV; Fe/S II, -303 +/- 15mV; FAD/FADH-; -351 +/- 20mV; FADH/FADH2, -236 +/-mV; Mo(VI)/Mo(V) (Rapid), -355 +/- 20mV; Mo(V) (Rapid)/Mo(IV), -355 +/- 20mV. 2. Behaviour of the functional enzyme is essentially ideal in Tris but less so in pyrophosphate. In Tris, the potential for Mo(VI)/Mo(V) (Rapid) is lowered relative to that in pyrophosphate, but the potential for Fe/S II is raised. The influence of buffer on the potentials was investigated by partial-reduction experiments with six other buffers. 3. Conversion of the enzyme with cyanide into the non-functional form, which gives the Slow molybdenum signal, or alkylation of FAD, has little effect on the mid-point potentials of the other centres. The potentials associated with the Slow signal are: Mo(VI)/Mo(V) (Slow), -440 +/- 25mV; Mo(V) (Slow)/Mo(IV), -480 +/- 25 mV. This signal exhibits very sluggish equilibration with the mediator system. 4. The deviations from ideal behaviour are discussed in terms of possible binding of buffer ions or anti-co-operative interactions amongst the redox centres."}
{"id": "PMID:183753", "title": "Mitochondrial glycerol kinase activity in rat brain.", "content": "Glycerol kinase activity was found in the particulate fraction of rat brain homogenates predominantly associated with mitochondria. The enzyme remained bound to the particulate fraction after treatment with a variety of solubilizing agents.", "contents": "Mitochondrial glycerol kinase activity in rat brain. Glycerol kinase activity was found in the particulate fraction of rat brain homogenates predominantly associated with mitochondria. The enzyme remained bound to the particulate fraction after treatment with a variety of solubilizing agents."}
{"id": "PMID:183754", "title": "Effects of calcium ions and the bivalent cation ionophore A23187 on the agglutination and fusion of chicken erythrocytes by Sendai virus.", "content": "1. Ca2+ (0.4-16 mM) had no detectable action on the agglutination of hen erythrocytes by Sendai virus. 2. Pretreatment of the cells with Ca2+ (0.1-8 mM) in the presence of the bivalent cation ionophore A23187 led, however, to a significant decrease in the subsequent agglutination of the cells by the virus. 3. It thus appears that the entry of Ca2+ into the interior of these cells decreases cellular agglutination by Sendai virus; possible interpretations of this phenomenon are discussed in terms of the movement of intramembranous particles. 4. With a small number of virions, maximum cell fusion by Sendai virus occurred in the presence of EGTA [ethanedioxybis(ethylamine)tetra-acetate]. 5. Virus-induced cell fusion was significantly decreased by Ca2+, even at a concentration of 0.2 mM; it is suggested that this may result from diminished interactions between virus particles and erythrocyte membranes.", "contents": "Effects of calcium ions and the bivalent cation ionophore A23187 on the agglutination and fusion of chicken erythrocytes by Sendai virus. 1. Ca2+ (0.4-16 mM) had no detectable action on the agglutination of hen erythrocytes by Sendai virus. 2. Pretreatment of the cells with Ca2+ (0.1-8 mM) in the presence of the bivalent cation ionophore A23187 led, however, to a significant decrease in the subsequent agglutination of the cells by the virus. 3. It thus appears that the entry of Ca2+ into the interior of these cells decreases cellular agglutination by Sendai virus; possible interpretations of this phenomenon are discussed in terms of the movement of intramembranous particles. 4. With a small number of virions, maximum cell fusion by Sendai virus occurred in the presence of EGTA [ethanedioxybis(ethylamine)tetra-acetate]. 5. Virus-induced cell fusion was significantly decreased by Ca2+, even at a concentration of 0.2 mM; it is suggested that this may result from diminished interactions between virus particles and erythrocyte membranes."}
{"id": "PMID:183755", "title": "The properties of the primary electron acceptor in the Photosystem I reaction centre of spinach chloroplasts and its interaction with P700 and the bound ferredoxin in various oxidation-reduction states.", "content": "The properties of the component 'X' identified as the primary electron acceptor of Photosystem I in spinach was investigated by electron-paramagnetic-resonance spectroscopy and the complete spectrum obtained for the first time. Component 'X' has gx = 1.78, gy = 1.88 and gz = 2.08; it can be observed only at very low temperatures (8--13K) and high microwave powers. Component X was identified in Photosystem I particles prepared with the French press or with Triton X-100. In samples reduced with ascorbate, illumination at low temperatures results in the photo-oxidation of P700 and reduction of a bound iron-sulphur protein; this is irreversible at low temperature. In samples in which the iron-sulphur proteins are reduced by sodium dithionite, illumination at low temperature results in the oxidation of P700 and the reduction of component 'X'; this is reversible at low temperature. The light-induced P700 signal is the same size with either ascorbate or dithionite as reducing agent, showing that all of the P700 involved in reduction of bound ferredoxin also functions in the reduction of component 'X'.", "contents": "The properties of the primary electron acceptor in the Photosystem I reaction centre of spinach chloroplasts and its interaction with P700 and the bound ferredoxin in various oxidation-reduction states. The properties of the component 'X' identified as the primary electron acceptor of Photosystem I in spinach was investigated by electron-paramagnetic-resonance spectroscopy and the complete spectrum obtained for the first time. Component 'X' has gx = 1.78, gy = 1.88 and gz = 2.08; it can be observed only at very low temperatures (8--13K) and high microwave powers. Component X was identified in Photosystem I particles prepared with the French press or with Triton X-100. In samples reduced with ascorbate, illumination at low temperatures results in the photo-oxidation of P700 and reduction of a bound iron-sulphur protein; this is irreversible at low temperature. In samples in which the iron-sulphur proteins are reduced by sodium dithionite, illumination at low temperature results in the oxidation of P700 and the reduction of component 'X'; this is reversible at low temperature. The light-induced P700 signal is the same size with either ascorbate or dithionite as reducing agent, showing that all of the P700 involved in reduction of bound ferredoxin also functions in the reduction of component 'X'."}
{"id": "PMID:183785", "title": "[Azidocillin: activity in vitro, pharmacokinetics and therapeutic results in whooping cough].", "content": "In vitro activities of acidocillin and ampicillin were compared in 20 strains of Haemophilus influenzae, 50 strains of Enterococci and 4 strains of Bordetella pertussis by serial dilution test. There were no significant differences between both antibiotics. On Staphylococcus aureus (100 strains) and Streptococcus group A (25 strains) acidocillin was effective at the same degree as phenoxymethylpenicillin. After oral administration of 0.75 g acidocillin (1 h after a standard breakfast) serum peaks in 10 healthy adults were 6.1 +/- 0.51 mug/ml (after 1 1/2 h) which decreased to 0.5 +/- 0.10 mug/ml (after 4 h) and to 0.045 +/- 0.02 mug/ml (after 6 h). Urine-recovery in 9 h after oral administration of 0.75 g was found as of 58%, after i.v. administration of the same dose 78% (absorption rate nearly 74%). Therapy of whooping cough in 12 children with acidocillin (60 mg/kg/die) led to the disappearance of Bordetella pertussis from nasal swabs (only one failure caused by the child's frequent vomiting).", "contents": "[Azidocillin: activity in vitro, pharmacokinetics and therapeutic results in whooping cough]. In vitro activities of acidocillin and ampicillin were compared in 20 strains of Haemophilus influenzae, 50 strains of Enterococci and 4 strains of Bordetella pertussis by serial dilution test. There were no significant differences between both antibiotics. On Staphylococcus aureus (100 strains) and Streptococcus group A (25 strains) acidocillin was effective at the same degree as phenoxymethylpenicillin. After oral administration of 0.75 g acidocillin (1 h after a standard breakfast) serum peaks in 10 healthy adults were 6.1 +/- 0.51 mug/ml (after 1 1/2 h) which decreased to 0.5 +/- 0.10 mug/ml (after 4 h) and to 0.045 +/- 0.02 mug/ml (after 6 h). Urine-recovery in 9 h after oral administration of 0.75 g was found as of 58%, after i.v. administration of the same dose 78% (absorption rate nearly 74%). Therapy of whooping cough in 12 children with acidocillin (60 mg/kg/die) led to the disappearance of Bordetella pertussis from nasal swabs (only one failure caused by the child's frequent vomiting)."}
{"id": "PMID:183786", "title": "[Qualitative and quantitative histoenzymatic study on isoproterenol induced myocardial necroses in rats (author's transl)].", "content": "By means of a 2-day s.c. application of 60 mg/kg isoproterenol in Wistar rats reproducible myocardium necroses with a characteristic topography were induced. The lesions were particularly found in the sub-endocardial area, penetrating intramurally into the wall of the left ventricle and spreading to the papillary muscle, the area of the apex of the heart, and they also appeared in the neighbourhood of the coronary arteries. The quantitative and qualitative histo-enzymatic determinations of the activity of oxydative mitochondrial enzymes, cytochromoxydase and succinatedehydrogenase do not only show a marked decrease of activity in the area of lesions proved by histopathological investigations, but also very sensitively demonstrate a beginning myocardial hypoxia in such areas which in histopathological tests only show light to medium infiltrations and above that also signify clearly that in the neighbourhood of the lesions a compensatory increase of the oxydative metabolism is found. The possibility of using myocardial necroses in rats, induced by the application of isopreterenol, as a model for the experimental study of new heart and coronary drugs, is discussed.", "contents": "[Qualitative and quantitative histoenzymatic study on isoproterenol induced myocardial necroses in rats (author's transl)]. By means of a 2-day s.c. application of 60 mg/kg isoproterenol in Wistar rats reproducible myocardium necroses with a characteristic topography were induced. The lesions were particularly found in the sub-endocardial area, penetrating intramurally into the wall of the left ventricle and spreading to the papillary muscle, the area of the apex of the heart, and they also appeared in the neighbourhood of the coronary arteries. The quantitative and qualitative histo-enzymatic determinations of the activity of oxydative mitochondrial enzymes, cytochromoxydase and succinatedehydrogenase do not only show a marked decrease of activity in the area of lesions proved by histopathological investigations, but also very sensitively demonstrate a beginning myocardial hypoxia in such areas which in histopathological tests only show light to medium infiltrations and above that also signify clearly that in the neighbourhood of the lesions a compensatory increase of the oxydative metabolism is found. The possibility of using myocardial necroses in rats, induced by the application of isopreterenol, as a model for the experimental study of new heart and coronary drugs, is discussed."}
{"id": "PMID:183787", "title": "Protecting action of aspartate on the hepatic changes induced by D-galactosamine.", "content": "The protective action of aspartic acid on isolated and perfused rat liver was studied. In case of D-galactosamine intoxication the GOT, GPT and SDH activity and the lactate and pyruvate concentration in the perfusion medium were less augmented and the glycogen level in hepatic tissue was less diminished in animals treated with aspartic acid, as compared to controls. The histochemical applied (PAS reaction for glycogen, nucleic acids, NADH2-diaphorase, glucose-6-phosphatase and membrane-ATP-ase), also stated a protecting effect in the treated animals. The protective action of aspartate is hypothetically considered to be exerted by its capacity to reestablish the cellular deficit of pyridine nucleotides and thus to improve the synthesis of nucleic acids, glycoprotein and glycolipids or/and by its participation in various metabolic pathways.", "contents": "Protecting action of aspartate on the hepatic changes induced by D-galactosamine. The protective action of aspartic acid on isolated and perfused rat liver was studied. In case of D-galactosamine intoxication the GOT, GPT and SDH activity and the lactate and pyruvate concentration in the perfusion medium were less augmented and the glycogen level in hepatic tissue was less diminished in animals treated with aspartic acid, as compared to controls. The histochemical applied (PAS reaction for glycogen, nucleic acids, NADH2-diaphorase, glucose-6-phosphatase and membrane-ATP-ase), also stated a protecting effect in the treated animals. The protective action of aspartate is hypothetically considered to be exerted by its capacity to reestablish the cellular deficit of pyridine nucleotides and thus to improve the synthesis of nucleic acids, glycoprotein and glycolipids or/and by its participation in various metabolic pathways."}
{"id": "PMID:183788", "title": "Atilipidemic drugs. Part 5: Evaluation of the hypolipidemic effect of LF 178 in 191 patients affected by the atherogenic form of endogenous hyperlipoproteinemia (types IIa, IIb and IV).", "content": "The effect of isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]-propionate (LF 178; procetofene; Lipanthyl), a new hypolipidemic agent, has been evaluated in 191 patients affected by endogenous hyperlipoproteinemia (IIa, IIb and IV). Data were collected from patients on active drug trial from 1 to 18 months. The daily administered dose varied from 200 to 400 mg according to pretreatment dietary stabilized lipid values. Under the controlled experimental conditions described, LF-178 lowered cholesterol by 20 to 36% in types IIa and IIb and triglycerides by 30 to 50% in types IIa and IV of H. L. P. A comparative trial of LF 178 and clofibrate indicates that the drug is significantly more potent than the reference compound after 1 month of treatment. Tolerance has always been excellent throughout the study.", "contents": "Atilipidemic drugs. Part 5: Evaluation of the hypolipidemic effect of LF 178 in 191 patients affected by the atherogenic form of endogenous hyperlipoproteinemia (types IIa, IIb and IV). The effect of isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]-propionate (LF 178; procetofene; Lipanthyl), a new hypolipidemic agent, has been evaluated in 191 patients affected by endogenous hyperlipoproteinemia (IIa, IIb and IV). Data were collected from patients on active drug trial from 1 to 18 months. The daily administered dose varied from 200 to 400 mg according to pretreatment dietary stabilized lipid values. Under the controlled experimental conditions described, LF-178 lowered cholesterol by 20 to 36% in types IIa and IIb and triglycerides by 30 to 50% in types IIa and IV of H. L. P. A comparative trial of LF 178 and clofibrate indicates that the drug is significantly more potent than the reference compound after 1 month of treatment. Tolerance has always been excellent throughout the study."}
{"id": "PMID:183789", "title": "Antilipidemic drugs. Part 6: LF 178 in man. A preliminary note on a multicenter investigation bearing on 393 subjects with pure or mixed forms of hyperlipidemia.", "content": "A total of 393 patients affected by different foms of hyperlipoproteinemia have been treated for up to 12 months or more with a daily dose of 200-400 mg of isopropyl-4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]-propionate (LF 178; procetofene; Lipanthyl). In pure hypercholesterolemia (IIa) the mean depression of cholesterol exceeded 26% and the drug induced degree of normalization was 85%. In mixed hypercholesterolemia (IIa) cholesterol was depressed by 23% and triglycerides by approximately 40%. In major affections of hypercholesterolemia (cholesterol > 3.5 gll) the mean induced depression exceeded 30%. Pure hypertriglyceridemia (IV) was strongly affected by the drug LF 178 induced a mean depression of triglycerides exceeding 60% after 6 months of treatment. In all cases the antilipidemic effect was fast and well sustained...", "contents": "Antilipidemic drugs. Part 6: LF 178 in man. A preliminary note on a multicenter investigation bearing on 393 subjects with pure or mixed forms of hyperlipidemia. A total of 393 patients affected by different foms of hyperlipoproteinemia have been treated for up to 12 months or more with a daily dose of 200-400 mg of isopropyl-4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl]-propionate (LF 178; procetofene; Lipanthyl). In pure hypercholesterolemia (IIa) the mean depression of cholesterol exceeded 26% and the drug induced degree of normalization was 85%. In mixed hypercholesterolemia (IIa) cholesterol was depressed by 23% and triglycerides by approximately 40%. In major affections of hypercholesterolemia (cholesterol > 3.5 gll) the mean induced depression exceeded 30%. Pure hypertriglyceridemia (IV) was strongly affected by the drug LF 178 induced a mean depression of triglycerides exceeding 60% after 6 months of treatment. In all cases the antilipidemic effect was fast and well sustained..."}
{"id": "PMID:183790", "title": "[Investigation of adrenal function with corticotrophin-(1-23)-tricosipeptide-amide (author's transl)].", "content": "The new peptide corticotrophin-(1-23)-tricosipeptide-amide (Acethropan S) was shown to be useful in the assessment of adrenal function. Both in normal subjects and patients with adrenal insufficiency, the cortisol releasing capacity could be better evaluated with a dosage of 0.5 mg than with 0.25 mg. There were no obvious side effects induced by corticotrophin-(1-23)-tricosipeptide-amide.", "contents": "[Investigation of adrenal function with corticotrophin-(1-23)-tricosipeptide-amide (author's transl)]. The new peptide corticotrophin-(1-23)-tricosipeptide-amide (Acethropan S) was shown to be useful in the assessment of adrenal function. Both in normal subjects and patients with adrenal insufficiency, the cortisol releasing capacity could be better evaluated with a dosage of 0.5 mg than with 0.25 mg. There were no obvious side effects induced by corticotrophin-(1-23)-tricosipeptide-amide."}
{"id": "PMID:183792", "title": "[Studies on the stability of human ultradian rhythms (author's transl)].", "content": "It was investigated whether the REM-NREM (rapid eye movement-non-REM) sleep rhythm has a stable period during long-term observations. Sequences of 17 to 31 consecutive sleep records were analyzed for 6 test subjects and 1 patient. Period stability was confirmed for three experimental conditions: a) undisturbed night sleep, b) inversion of the sleep-waking cycle, c) absence of external timing mechanisms. The period of the ultradian REM sleep rhythm is no integral submultiple of 24 h, so that the remainder causes a daily drift in the REM sleep rhythm. It is assumed that the ultradian process is controlled endogenously. In contrast to the circadian rhythm the ultradian rhythm appears to be free-running under normal conditions. The stability of the ultradian period has been shown in long-term observations.", "contents": "[Studies on the stability of human ultradian rhythms (author's transl)]. It was investigated whether the REM-NREM (rapid eye movement-non-REM) sleep rhythm has a stable period during long-term observations. Sequences of 17 to 31 consecutive sleep records were analyzed for 6 test subjects and 1 patient. Period stability was confirmed for three experimental conditions: a) undisturbed night sleep, b) inversion of the sleep-waking cycle, c) absence of external timing mechanisms. The period of the ultradian REM sleep rhythm is no integral submultiple of 24 h, so that the remainder causes a daily drift in the REM sleep rhythm. It is assumed that the ultradian process is controlled endogenously. In contrast to the circadian rhythm the ultradian rhythm appears to be free-running under normal conditions. The stability of the ultradian period has been shown in long-term observations."}
{"id": "PMID:183793", "title": "[Pharmacological investigations of 4'-fluoro-4-(4-methyl-peperidono)-butyrophenone with respect to its sedative and sleep-inducing properties (author's transl)].", "content": "The butyrophenone melperone (Eunerpan) in mice and rats caused a prominetn inhibition of spontaneous activity, whereas cataleptogenic and apomorphine-antagonistic properties were less pronounced. In rats the sleep-cycle was altered: decrease of wakefulness, increase of slow-wave sleep and a moderate reduction of rapid eye movement-(REM) sleep. In contrast to thioridazine and chlorpromazine the effect lasted only for 4 h, followed by a slight REM rebound. In rabbits melperone caused a decrease of muscle tone and with somewhat higher doses an inhibition of the arousal-reaction. As seen by the computerized spontaneous cortical EEG, dosages below 1 mg/kg caused a shift of the dominant frequency from theta- to delta-rhythm and an increase of power. Therefore the neuropharmacological pattern of the butyrophenone melperone is closely related to those of thioridazine or chlorpromazine, without, however, having their long action.", "contents": "[Pharmacological investigations of 4'-fluoro-4-(4-methyl-peperidono)-butyrophenone with respect to its sedative and sleep-inducing properties (author's transl)]. The butyrophenone melperone (Eunerpan) in mice and rats caused a prominetn inhibition of spontaneous activity, whereas cataleptogenic and apomorphine-antagonistic properties were less pronounced. In rats the sleep-cycle was altered: decrease of wakefulness, increase of slow-wave sleep and a moderate reduction of rapid eye movement-(REM) sleep. In contrast to thioridazine and chlorpromazine the effect lasted only for 4 h, followed by a slight REM rebound. In rabbits melperone caused a decrease of muscle tone and with somewhat higher doses an inhibition of the arousal-reaction. As seen by the computerized spontaneous cortical EEG, dosages below 1 mg/kg caused a shift of the dominant frequency from theta- to delta-rhythm and an increase of power. Therefore the neuropharmacological pattern of the butyrophenone melperone is closely related to those of thioridazine or chlorpromazine, without, however, having their long action."}
{"id": "PMID:183794", "title": "[Effects of levodopa and piribedil on cyclic AMP levels in cerebrospinal fluid in rats (author's transl)].", "content": "30 min after injection of levodopa (200 mg/kg) into rats the cAMP levels in the cisternal fluid were significantly elevated by 60% over controls. When dopamine-beta-hydroxylase was inhibited by bis-(4-methyl-1-homopiperazinyl-thiocarbonyl)-disulfide (Fla 63) the levodopa induced increase of cAMP levels was less marked, it was suppressed by propranolol (10 mg/kg), a beta-adrenergic blocking agent. Piribedil (10 mg/kg) failed to influence cisternal cAMP concentrations. The findings do not support the concept of a dopamine-sensitive adenylate cyclase in vivo, and suggest a beta-adrenergic stimulation of cerebral adenylate cyclase by metabolites of levodopa.", "contents": "[Effects of levodopa and piribedil on cyclic AMP levels in cerebrospinal fluid in rats (author's transl)]. 30 min after injection of levodopa (200 mg/kg) into rats the cAMP levels in the cisternal fluid were significantly elevated by 60% over controls. When dopamine-beta-hydroxylase was inhibited by bis-(4-methyl-1-homopiperazinyl-thiocarbonyl)-disulfide (Fla 63) the levodopa induced increase of cAMP levels was less marked, it was suppressed by propranolol (10 mg/kg), a beta-adrenergic blocking agent. Piribedil (10 mg/kg) failed to influence cisternal cAMP concentrations. The findings do not support the concept of a dopamine-sensitive adenylate cyclase in vivo, and suggest a beta-adrenergic stimulation of cerebral adenylate cyclase by metabolites of levodopa."}
{"id": "PMID:183795", "title": "[Adenylat-kinase-Systeme, ein Beitrag zum manisch-depressiven Kranksein (MDK)].", "content": "Adenylate-kinase (AK) interacts in the balance of phosphate acceptors and donators. With respect to the polymorphism of enzyms of erythrocytes there can be assumed a system of two co-dominate allels determined by the genotype of AK 1 and AK 2 with the phenotypes of AK 1-1, AK 2-1 and AK 2-2. The distribution of AK within 108 cases of MDS and 90 controls was examined. AK 2-1 was found in about 30% of bipolar MDS, but in no case of unipolar MDS or controls. The possible relations were discussed demonstrating a synopsis of the pathogenesis of MDS.", "contents": "[Adenylat-kinase-Systeme, ein Beitrag zum manisch-depressiven Kranksein (MDK)]. Adenylate-kinase (AK) interacts in the balance of phosphate acceptors and donators. With respect to the polymorphism of enzyms of erythrocytes there can be assumed a system of two co-dominate allels determined by the genotype of AK 1 and AK 2 with the phenotypes of AK 1-1, AK 2-1 and AK 2-2. The distribution of AK within 108 cases of MDS and 90 controls was examined. AK 2-1 was found in about 30% of bipolar MDS, but in no case of unipolar MDS or controls. The possible relations were discussed demonstrating a synopsis of the pathogenesis of MDS."}
{"id": "PMID:183799", "title": "Pharmacodynamics of tubocurarine in humans.", "content": "The pharmacodynamics of neuromuscular transmission, following blockade by a single i.v. dose of tubocurarine (dtc) in humans, were simulated from experimental serum dtc concentration versus time data and serum dtc concentration versus percentage recovery data. Good agreement was obtained between the simulated and experimental time course of recovery at five different therapeutic doses. The initial apparent volume of distribution (Vapp) of dtc was approximately the same as the serum volume and appeared to increase with the size of the dose. These results were consistent with the suggestion that a greater fraction of the dose of dtc was distributed in non-vascular spaces or bound to tissue at larger doses. A pharmacodynamic working model using an average Vapp of 2848 ml simulated times up to 40% recovery within 15-20% error for doses of dtc of 0.30 mg/kg or less.", "contents": "Pharmacodynamics of tubocurarine in humans. The pharmacodynamics of neuromuscular transmission, following blockade by a single i.v. dose of tubocurarine (dtc) in humans, were simulated from experimental serum dtc concentration versus time data and serum dtc concentration versus percentage recovery data. Good agreement was obtained between the simulated and experimental time course of recovery at five different therapeutic doses. The initial apparent volume of distribution (Vapp) of dtc was approximately the same as the serum volume and appeared to increase with the size of the dose. These results were consistent with the suggestion that a greater fraction of the dose of dtc was distributed in non-vascular spaces or bound to tissue at larger doses. A pharmacodynamic working model using an average Vapp of 2848 ml simulated times up to 40% recovery within 15-20% error for doses of dtc of 0.30 mg/kg or less."}
{"id": "PMID:183800", "title": "Cardiovascular and neuromuscular effects of dimethyl tubocurarine in anaesthetized cats and rhesus monkeys.", "content": "Intravenous dose-response relationships for dimethyl tubocurarine showed that vagal blockade only became appreciable (50-83%) at doses 8-16 times those sufficient for full neuromuscular paralysis in anaesthetized cats (0.0625 mg/kg) and rhesus monkeys (0.125 mg/kg); heart rate was unchanged. Sympathetic function was unimpaired by supramaximal paralysing doses of 0.5 and 1 mg/kg in cats, but was reduced (20-41%) by comparable neuromuscular paralysing doses of 1 and 2 mg/kg in rhesus monkeys; these doses decreased carotid arterial pressure by 22-36%. The duration of action of dimethyl tubocurarine was prolonged; more than 60 min was required for recovery from full neuromuscular paralysis; the drug was even more persistent in rhesus monkeys than in cats. Thus the need remains for a drug resembling dimethyl tubocurarine in its highly specific action at the neuromuscular junction, but with a much shorter duration of action.", "contents": "Cardiovascular and neuromuscular effects of dimethyl tubocurarine in anaesthetized cats and rhesus monkeys. Intravenous dose-response relationships for dimethyl tubocurarine showed that vagal blockade only became appreciable (50-83%) at doses 8-16 times those sufficient for full neuromuscular paralysis in anaesthetized cats (0.0625 mg/kg) and rhesus monkeys (0.125 mg/kg); heart rate was unchanged. Sympathetic function was unimpaired by supramaximal paralysing doses of 0.5 and 1 mg/kg in cats, but was reduced (20-41%) by comparable neuromuscular paralysing doses of 1 and 2 mg/kg in rhesus monkeys; these doses decreased carotid arterial pressure by 22-36%. The duration of action of dimethyl tubocurarine was prolonged; more than 60 min was required for recovery from full neuromuscular paralysis; the drug was even more persistent in rhesus monkeys than in cats. Thus the need remains for a drug resembling dimethyl tubocurarine in its highly specific action at the neuromuscular junction, but with a much shorter duration of action."}
{"id": "PMID:183797", "title": "Membranous nephropathy long-term follow-up and association with neoplasia.", "content": "A ten years follow-up has been made on 66 patients with membranous glomerulonephritis. Eighty per cent of them showed nephrotic syndrome, one third elevated diastolic pressure and in 50% of the patients the GFR was reduced. Histopathologic stating and evolution were made as described by Ehrenreich histology with clinic and prognosis. Seven of 76 cases (11%) showed association with neoplasia; different pathogenetic hypothesis could be risen by this observation. The five year survival was 84% and the ten year survival about 50%. Increasing age and the presence of nephrotic syndrome mainly contribute to a poor prognosis.", "contents": "Membranous nephropathy long-term follow-up and association with neoplasia. A ten years follow-up has been made on 66 patients with membranous glomerulonephritis. Eighty per cent of them showed nephrotic syndrome, one third elevated diastolic pressure and in 50% of the patients the GFR was reduced. Histopathologic stating and evolution were made as described by Ehrenreich histology with clinic and prognosis. Seven of 76 cases (11%) showed association with neoplasia; different pathogenetic hypothesis could be risen by this observation. The five year survival was 84% and the ten year survival about 50%. Increasing age and the presence of nephrotic syndrome mainly contribute to a poor prognosis."}
{"id": "PMID:183803", "title": "Transformation of primary hamster embryo fibroblasts by type 2 simplex virus: evidence for a \"hit and run\" mechanism.", "content": "The phenomenon of cell transformation by type 2 herpes simplex virus has been investigated. Primary hamster embryo fibroblasts were exposed to type 2 herpes virus under conditions which would restrict or inhibit the lytic events of virus-cell interaction. Cell lines were established by single-cell cloning. There was evidence of altered cell morphology with altered biological activity in terms of longevity and oncogenicity; there was, however, no evidence of virus specific antigen or incorporation of viral nucleic acid into the host cell genome. Virus specific antigen was only detected in the early passages of an uncloned transformed cell line. We are thus unable to confirm previous studies (vide supra) and are obliged to propose a \"hit and run\" model for in vitro cell transformation by type 2 herpes simplex virus.", "contents": "Transformation of primary hamster embryo fibroblasts by type 2 simplex virus: evidence for a \"hit and run\" mechanism. The phenomenon of cell transformation by type 2 herpes simplex virus has been investigated. Primary hamster embryo fibroblasts were exposed to type 2 herpes virus under conditions which would restrict or inhibit the lytic events of virus-cell interaction. Cell lines were established by single-cell cloning. There was evidence of altered cell morphology with altered biological activity in terms of longevity and oncogenicity; there was, however, no evidence of virus specific antigen or incorporation of viral nucleic acid into the host cell genome. Virus specific antigen was only detected in the early passages of an uncloned transformed cell line. We are thus unable to confirm previous studies (vide supra) and are obliged to propose a \"hit and run\" model for in vitro cell transformation by type 2 herpes simplex virus."}
{"id": "PMID:183804", "title": "The fine structure of blood vessels in ethylnitrosourea-induced tumours of the rat nervous system: with special reference to the breakdown of the blood-brain barrier.", "content": "The fine structure of capillaries in and around ethylnitrosourea-induced tumours, gliomas and schwannomas, was examined in rats. A great variation was observed in the severity of changes: the degree of abnormality depended on the histological type and size of the tumour and on the site of the capillaries within the neoplasm. Endothelial cells, basement membranes and pericytes all demonstrated changes in their fine structure. The most striking alterations occurred in the endothelial cells: luminal cell membranes, tight junctions and pinocytotic activity were all modified. The widened extracellular spaces, particularly around capillaries, were frequently seen to contain proteinaceous material and haematogenous cells. Invasion of these spaces by neoplastic cells, however, rarely occurred. Formation of new capillaries was indicated by the mitotic activity of endothelial cells. These changes in the blood vessels of cerebral tumours have an important role in the breakdown of the blood-brain barrier.", "contents": "The fine structure of blood vessels in ethylnitrosourea-induced tumours of the rat nervous system: with special reference to the breakdown of the blood-brain barrier. The fine structure of capillaries in and around ethylnitrosourea-induced tumours, gliomas and schwannomas, was examined in rats. A great variation was observed in the severity of changes: the degree of abnormality depended on the histological type and size of the tumour and on the site of the capillaries within the neoplasm. Endothelial cells, basement membranes and pericytes all demonstrated changes in their fine structure. The most striking alterations occurred in the endothelial cells: luminal cell membranes, tight junctions and pinocytotic activity were all modified. The widened extracellular spaces, particularly around capillaries, were frequently seen to contain proteinaceous material and haematogenous cells. Invasion of these spaces by neoplastic cells, however, rarely occurred. Formation of new capillaries was indicated by the mitotic activity of endothelial cells. These changes in the blood vessels of cerebral tumours have an important role in the breakdown of the blood-brain barrier."}
{"id": "PMID:183805", "title": "Organ culture studies on the efficiency of infection of chicken tissues with avian infectious bronchitis virus.", "content": "Long-term organ cultures of a range of tissues collected from specific pathogen-free chickens were employed to determine their susceptibility, and their capacity for subsequent virus production, following inoculation with avian infectious bronchitis (AIB) virus. When inoculated with approximately 2-0 log10 median ciliostatic doses (CD50) of a classical highly egg-adapted vaccine strain (H120) of AIB virus, 9 of 23 tissues were shown to be susceptible, namely the nasal turbinates, trachea, air sac membranes,lungsasal turbinates, trachea, air sac membranes, lungs, proventriculus mucosa, thyroid, kidney, ovary and oviduct. When the remaining 14 tissues were inoculated with a high dose of virus (6.8 log10 CD50), the conjunctiva, caecel tonsil, testis and bursa of Fabricius were susceptible whereas the oesophagus and cloaca responded minimally. Inoculation of the same range of tissues with a high or low dose of a field strain (HVI9) of AIB virus produced similar results, except for a number of individual variations in response, due possibly to strain differences in pathogenicity. Determinations of the minimal infectious dose requirements of the susceptible tissues revealed that the efficiency of infection with the H120 strain was highest for the nasal turbinate and tracheal tissues, and thereafter, in order of decreasing efficiency, were the air sac membranes, lung, oviduct, proventriculus mucosa, conjunctiva, kidney, ovary, bursa of Fabricius, thyroid, testis, caecal tonsil, cloaca and oesophagus. The relevance of these results is discussed in connection with the early events in the pathogenesis and the clinical syndrome of AIB infection in chickens.", "contents": "Organ culture studies on the efficiency of infection of chicken tissues with avian infectious bronchitis virus. Long-term organ cultures of a range of tissues collected from specific pathogen-free chickens were employed to determine their susceptibility, and their capacity for subsequent virus production, following inoculation with avian infectious bronchitis (AIB) virus. When inoculated with approximately 2-0 log10 median ciliostatic doses (CD50) of a classical highly egg-adapted vaccine strain (H120) of AIB virus, 9 of 23 tissues were shown to be susceptible, namely the nasal turbinates, trachea, air sac membranes,lungsasal turbinates, trachea, air sac membranes, lungs, proventriculus mucosa, thyroid, kidney, ovary and oviduct. When the remaining 14 tissues were inoculated with a high dose of virus (6.8 log10 CD50), the conjunctiva, caecel tonsil, testis and bursa of Fabricius were susceptible whereas the oesophagus and cloaca responded minimally. Inoculation of the same range of tissues with a high or low dose of a field strain (HVI9) of AIB virus produced similar results, except for a number of individual variations in response, due possibly to strain differences in pathogenicity. Determinations of the minimal infectious dose requirements of the susceptible tissues revealed that the efficiency of infection with the H120 strain was highest for the nasal turbinate and tracheal tissues, and thereafter, in order of decreasing efficiency, were the air sac membranes, lung, oviduct, proventriculus mucosa, conjunctiva, kidney, ovary, bursa of Fabricius, thyroid, testis, caecal tonsil, cloaca and oesophagus. The relevance of these results is discussed in connection with the early events in the pathogenesis and the clinical syndrome of AIB infection in chickens."}
{"id": "PMID:183806", "title": "Replication of type 2 herpes simplex virus in human endocervical tissue in organ culture.", "content": "The replication of type 2 herpes simplex virus in human endocervical tissue in organ culture was investigated. The temporal profile of virus replication was related to the initial virus inoculum; high input inocula induced a rapid increase in virus titre while lower multiplicities induced a more slow-rising increase in virus titre. Our evidence suggested that explants were capable of initiating and supporting virus replication for at least 2 weeks following establishment of the culture. Virus yields were optimal when explants were cultured at 37 degrees and in serum-supplemented medium. Explants also supported the replication of type 1 herpes simplex virus and a \"non-human\" herpes simplex virus (pseudo-rabies virus). The optimal conditions for replication of type 2 herpes simplex virus in human endocervical explants have been established and will provide a model permitting precise investigation of lytic or other virus-cervical cell interactions and their possible relationship to herpes virus-induced pre-invasive carcinoma of this organ.", "contents": "Replication of type 2 herpes simplex virus in human endocervical tissue in organ culture. The replication of type 2 herpes simplex virus in human endocervical tissue in organ culture was investigated. The temporal profile of virus replication was related to the initial virus inoculum; high input inocula induced a rapid increase in virus titre while lower multiplicities induced a more slow-rising increase in virus titre. Our evidence suggested that explants were capable of initiating and supporting virus replication for at least 2 weeks following establishment of the culture. Virus yields were optimal when explants were cultured at 37 degrees and in serum-supplemented medium. Explants also supported the replication of type 1 herpes simplex virus and a \"non-human\" herpes simplex virus (pseudo-rabies virus). The optimal conditions for replication of type 2 herpes simplex virus in human endocervical explants have been established and will provide a model permitting precise investigation of lytic or other virus-cervical cell interactions and their possible relationship to herpes virus-induced pre-invasive carcinoma of this organ."}
{"id": "PMID:183807", "title": "Cholesterol esterase activity in body fluids.", "content": "Antistreptolysin O activity (greater than or equal to 200 Todd units/ml) was found in 20% of 25 ascitic fluids, 20% of 55 pleural fluids and 37-5% of 56 joint fluids. These levels are not due to antibody but to the cholesterol moiety of altered beta-lipoproteins. The activity is precipitable with 10% dextran sulphate. Incubation of mixtures of fluids with titres less than 200 and normal human serum generated eight-fold or greater rises in antistreptolysin titres. This results from the activity of cholesterol esterase in the fluid acting on the beta-lipoprotein of the serum and activity was noted in 90% of ascitic fluids, 59% of pleural fluids and 54% of joint fluids. However, mixtures showing no such rise probably also contain esterase, the failure to demonstrate antistreptolysin activity being due to equilibration of ester derived cholesterol with sub-fractions of high density and very low density lipoproteins.", "contents": "Cholesterol esterase activity in body fluids. Antistreptolysin O activity (greater than or equal to 200 Todd units/ml) was found in 20% of 25 ascitic fluids, 20% of 55 pleural fluids and 37-5% of 56 joint fluids. These levels are not due to antibody but to the cholesterol moiety of altered beta-lipoproteins. The activity is precipitable with 10% dextran sulphate. Incubation of mixtures of fluids with titres less than 200 and normal human serum generated eight-fold or greater rises in antistreptolysin titres. This results from the activity of cholesterol esterase in the fluid acting on the beta-lipoprotein of the serum and activity was noted in 90% of ascitic fluids, 59% of pleural fluids and 54% of joint fluids. However, mixtures showing no such rise probably also contain esterase, the failure to demonstrate antistreptolysin activity being due to equilibration of ester derived cholesterol with sub-fractions of high density and very low density lipoproteins."}
{"id": "PMID:183808", "title": "Changes in tertiary structure accompanying a single base change in transfer RNA. Proton magnetic resonance and aminoacylation studies of Escherichia coli tRNAMet f1 and tRNAMet f3 and their spin-labeled (s4U8) derivatives.", "content": "The properties of Escherichia coli tRNAMet f1 and tRNAMet f3 that differ by only one base change, m7G to A at position 47, have been compared structurally by proton magnetic resonance and functionally by the aminoacylation reaction. The NMR spectra of the two tRNA species in the region between 0 and 4 ppm below 4,4-dimethyl-4-silapentane-1-sulfonic acid (DSS) (methyl and methylene region) were the same except for the absence of the lowest field peak at 3.8 ppm in tRNAMet f3, thus unequivocally identifying this resonance at the methyl group of m7G47 of tRNAMet f1. The same resonance disappears in tRNAMet f1 spin-labeled at s4U8 and reappears in the diamagnetic reduced spin-labeled tRNAMet f1 from which the average distance between the spin-label and the methyl protons of m7G is estimated to be less than 15 A. The proximity of m7G47 but not T55 to s4U8 in the structure of E. coli tRNAMet f1 in solution is consistant with the crystallographic model for yeast tRNAPhe. A spectral comparison of the hydrogen-bond regions (11-14 ppm below DSS) of tRNAMet f1 and tRNAMet f3 reveals major shifts of four resonances previously assigned to tertiary hydrogen bonds. Of the four, the one at lowest field (14.8 ppm) had been assigned by chemical modification to the tertiary (s4U8-A14) hydrogen bond and the one at 13.3 ppm had been tentatively assigned to the tertiary hydrogen bond G23-m7G47 of the 13-23-47 triple. A more positive assignment of the G23-m7G47 at 13.3 ppm could be made from the additional evidence that this resonance, which was first observed in the difference spectrum between spin-labeled tRNAMet f1 and its reduced form, is the only one missing in the analogous difference spectrum of tRNAMet f3. At low ionic strength and in the absence of magnesium ions, the differences in the hydrogen-bonded region of the NMR spectra of tRNAMet f1 and tRNAMet f3 are much greater than in the presence of magnesium ions. The optimal magnesium concentration required for maximal initial velocities is also higher for tRNAMet f3 than for tRNAMet f1. The perturbation caused by the spin-label in destabilizing hydrogen bonds in the region between 13 and 14 ppm is greater for tRNAMet f3 than tRNAMet f1 but the distance relations for the hydrogen bonds in the region between 12 and 13 ppm (the major paramagnetic perturbations) are conserved in the two species. The disruption of one hydrogen bond relative to native tRNAMet f1 either by spin-labeling (s4U8-A14) or by substitution of m7G by A in tRNAMet f3 has little effect on the aminoacyl acceptor activity or the velocity of the aminoacylation reaction at optimal magnesium concentration, but the absence of both tertiary hydrogen bonds in the augmented D-helix region in the spin-labeled tRNAMet f3 results in approximately 60% reduction both in acceptance activity and in initial velocity of the aminoacylation reaction.", "contents": "Changes in tertiary structure accompanying a single base change in transfer RNA. Proton magnetic resonance and aminoacylation studies of Escherichia coli tRNAMet f1 and tRNAMet f3 and their spin-labeled (s4U8) derivatives. The properties of Escherichia coli tRNAMet f1 and tRNAMet f3 that differ by only one base change, m7G to A at position 47, have been compared structurally by proton magnetic resonance and functionally by the aminoacylation reaction. The NMR spectra of the two tRNA species in the region between 0 and 4 ppm below 4,4-dimethyl-4-silapentane-1-sulfonic acid (DSS) (methyl and methylene region) were the same except for the absence of the lowest field peak at 3.8 ppm in tRNAMet f3, thus unequivocally identifying this resonance at the methyl group of m7G47 of tRNAMet f1. The same resonance disappears in tRNAMet f1 spin-labeled at s4U8 and reappears in the diamagnetic reduced spin-labeled tRNAMet f1 from which the average distance between the spin-label and the methyl protons of m7G is estimated to be less than 15 A. The proximity of m7G47 but not T55 to s4U8 in the structure of E. coli tRNAMet f1 in solution is consistant with the crystallographic model for yeast tRNAPhe. A spectral comparison of the hydrogen-bond regions (11-14 ppm below DSS) of tRNAMet f1 and tRNAMet f3 reveals major shifts of four resonances previously assigned to tertiary hydrogen bonds. Of the four, the one at lowest field (14.8 ppm) had been assigned by chemical modification to the tertiary (s4U8-A14) hydrogen bond and the one at 13.3 ppm had been tentatively assigned to the tertiary hydrogen bond G23-m7G47 of the 13-23-47 triple. A more positive assignment of the G23-m7G47 at 13.3 ppm could be made from the additional evidence that this resonance, which was first observed in the difference spectrum between spin-labeled tRNAMet f1 and its reduced form, is the only one missing in the analogous difference spectrum of tRNAMet f3. At low ionic strength and in the absence of magnesium ions, the differences in the hydrogen-bonded region of the NMR spectra of tRNAMet f1 and tRNAMet f3 are much greater than in the presence of magnesium ions. The optimal magnesium concentration required for maximal initial velocities is also higher for tRNAMet f3 than for tRNAMet f1. The perturbation caused by the spin-label in destabilizing hydrogen bonds in the region between 13 and 14 ppm is greater for tRNAMet f3 than tRNAMet f1 but the distance relations for the hydrogen bonds in the region between 12 and 13 ppm (the major paramagnetic perturbations) are conserved in the two species. The disruption of one hydrogen bond relative to native tRNAMet f1 either by spin-labeling (s4U8-A14) or by substitution of m7G by A in tRNAMet f3 has little effect on the aminoacyl acceptor activity or the velocity of the aminoacylation reaction at optimal magnesium concentration, but the absence of both tertiary hydrogen bonds in the augmented D-helix region in the spin-labeled tRNAMet f3 results in approximately 60% reduction both in acceptance activity and in initial velocity of the aminoacylation reaction."}
{"id": "PMID:183809", "title": "Lysine-sensitive aspartokinase of Escherichia coli K12. Synergy and autosynergy in an allosteric V system.", "content": "The interactions of the lysine-sensitive aspartokinase of E. coli K12 with lysine and leucine, as evidenced in the inhibition and binding curves, are well explained by the equations of an allosteric V model. Mathematical treatments of such a model lead to new linearized plots. These representations are applied to our experimental results and allow the direct determination of some parameters of the model (equilibrium constant L' and leucine dissociation constants). The other parameters are obtained by an optimization method. The theoretical curves drawn according to this model account well for the synergistic inhibition between lysine and leucine and for the role of the two nonequivalent lysine binding sites (\"autosynergy\").", "contents": "Lysine-sensitive aspartokinase of Escherichia coli K12. Synergy and autosynergy in an allosteric V system. The interactions of the lysine-sensitive aspartokinase of E. coli K12 with lysine and leucine, as evidenced in the inhibition and binding curves, are well explained by the equations of an allosteric V model. Mathematical treatments of such a model lead to new linearized plots. These representations are applied to our experimental results and allow the direct determination of some parameters of the model (equilibrium constant L' and leucine dissociation constants). The other parameters are obtained by an optimization method. The theoretical curves drawn according to this model account well for the synergistic inhibition between lysine and leucine and for the role of the two nonequivalent lysine binding sites (\"autosynergy\")."}
{"id": "PMID:183810", "title": "Electrophoretic analysis of substrate-attached proteins from normal and virus-transformed cells.", "content": "The proteins which have been left tightly bound to the tissue culture substrate after ethylenebis (oxyethyl-enenitrilo) tetraacetic acid (EGTA)-mediated removal of normal, virus-transformed, and revertant mouse cells and which have been implicated in the substrate adhesion process have been analyzed by slab sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three size classes of hyaluronate proteoglycans were resolved in the 5% well gel; approximately half of the protein in the substrate-attached material coelectrophoresed with these polysaccharides-so-called glycosaminoglycan-associated protein(GAP). A portion of the GAP was shown to be highly heterogeneous and displaced from the polysaccharide by preincubation with calf histone before electrophoresis. The relative proportions of the proteoglycans varied in material deposited during a variety of cellular attachment and growth conditions. The remainder of the cellular protein in substrate-attached material was resolved as several major and distinct protein bands in 8 or 20% separating gels (a limited number of distinct serum proteins have also been identified as substrate bound). Protein C0 (molecular weight 220 000) was a prominent component in the material from a variety of normal and virus-transformed cells and resembled the so-called LETS or CSP glycoprotein in several respects; protein Ca was myosin-like in several respects; protein C2 was shown to be actin; and protein C1 (molecular weight 56 000) does not appear to be tubulin. Histones were also present in most preparations of substrate-attached material, particularly at high levels in transformed cell meterial, and may result from EGTA-mediated leakiness of the cell and subsequent binding to the negatively charged polysaccharide. These substrate-attached proteins were (a) prominent in substrate-attached material from many cell types in characteristic relative proportions, (b) deposited by EGTA-subcultured cells during the first hour of attachment to fresh substrate, (c) deposited by cells growing on plastic or glass substrates (three additional) components were also prominent in glass-attached material), and (d) deposited during long-term growth on or initial attachment to substrates coated wit 3T3 substrate-attached material. Pulse-chase analyses with radioactive leucine indicated that these proteins exhibit different turn-over behaviors. These results are discussed with regard to the possible involvement of these substrate-attached proteins in the substrate adhesion process, with particular interest in the interaction of cytoskeletal microfilaments with other surface membrane components and with regard to alteration of substrate adhesion by virus transformation.", "contents": "Electrophoretic analysis of substrate-attached proteins from normal and virus-transformed cells. The proteins which have been left tightly bound to the tissue culture substrate after ethylenebis (oxyethyl-enenitrilo) tetraacetic acid (EGTA)-mediated removal of normal, virus-transformed, and revertant mouse cells and which have been implicated in the substrate adhesion process have been analyzed by slab sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Three size classes of hyaluronate proteoglycans were resolved in the 5% well gel; approximately half of the protein in the substrate-attached material coelectrophoresed with these polysaccharides-so-called glycosaminoglycan-associated protein(GAP). A portion of the GAP was shown to be highly heterogeneous and displaced from the polysaccharide by preincubation with calf histone before electrophoresis. The relative proportions of the proteoglycans varied in material deposited during a variety of cellular attachment and growth conditions. The remainder of the cellular protein in substrate-attached material was resolved as several major and distinct protein bands in 8 or 20% separating gels (a limited number of distinct serum proteins have also been identified as substrate bound). Protein C0 (molecular weight 220 000) was a prominent component in the material from a variety of normal and virus-transformed cells and resembled the so-called LETS or CSP glycoprotein in several respects; protein Ca was myosin-like in several respects; protein C2 was shown to be actin; and protein C1 (molecular weight 56 000) does not appear to be tubulin. Histones were also present in most preparations of substrate-attached material, particularly at high levels in transformed cell meterial, and may result from EGTA-mediated leakiness of the cell and subsequent binding to the negatively charged polysaccharide. These substrate-attached proteins were (a) prominent in substrate-attached material from many cell types in characteristic relative proportions, (b) deposited by EGTA-subcultured cells during the first hour of attachment to fresh substrate, (c) deposited by cells growing on plastic or glass substrates (three additional) components were also prominent in glass-attached material), and (d) deposited during long-term growth on or initial attachment to substrates coated wit 3T3 substrate-attached material. Pulse-chase analyses with radioactive leucine indicated that these proteins exhibit different turn-over behaviors. These results are discussed with regard to the possible involvement of these substrate-attached proteins in the substrate adhesion process, with particular interest in the interaction of cytoskeletal microfilaments with other surface membrane components and with regard to alteration of substrate adhesion by virus transformation."}
{"id": "PMID:183811", "title": "Annular lipids determine the ATPase activity of a calcium transport protein complexed with dipalmitoyllecithin.", "content": "Pure complexes of dipalmitoyllecithin (DPL, 16:0) which Ca2+, Mg2+ dependent ATPase from sarcoplasmic reticulum are unusual in retaining significant ATPase activity down to about 30 degrees C, well below the transition temperature of the pure lipid at 41 degrees C. A minimum of about 35 lipid molecules per ATPase is required to maintain maximal ATPase activity, but the complexes are progressively and irreversibly inactivated at lower lipid to protein ratios. Complexes containing more than the minimum lipid requirement show very similar temperature profiles of activity about 30 degrees C over a wide range of lipid to protein ratios, up to 1500:1. Spin-label studies indicate that, at lipid to protein ratios of less than about 30 lipids per ATPase, no DPL phase transition can be detected, but at all higher ratios, a phase transition occurs at about 41 degrees C. In all of these complexes there are breaks in the Arrhenius plots of ATPase activity at 27--32 degrees C and at 37.5--38.5 degrees C. Experiments with perturbing agents, such as cholesterol and benzyl alcohol which have well-defined effects on the DPL phase transition, indicate that these breaks in the Arrhenius plots of ATPase activity cannot be attributed to a depressed and broadened phase transition in the lipids near the protein molecules. These results are interpreted as evidence for a phospholipid annulus of at least 30 lipid molecules with interact directly with the ATPase and cannot undergo a phase transition at 41 degrees C. This structural interaction of the ATPase with the annular DPL molecules has a predominant effect in determining the form of the temperature-activity profiles. However, the perturbation of the DPL phase transition does not extend significantly beyond the annulus since a phase transition which starts at 41 degrees C can be detected as soon as extraannular lipid is present in the complexes. We suggest that it may be a general feature of membrane structure that penetrant membrane proteins interact with their immediate lipid environment so as to cause only a minimal perturbation of the lipid bilayer.", "contents": "Annular lipids determine the ATPase activity of a calcium transport protein complexed with dipalmitoyllecithin. Pure complexes of dipalmitoyllecithin (DPL, 16:0) which Ca2+, Mg2+ dependent ATPase from sarcoplasmic reticulum are unusual in retaining significant ATPase activity down to about 30 degrees C, well below the transition temperature of the pure lipid at 41 degrees C. A minimum of about 35 lipid molecules per ATPase is required to maintain maximal ATPase activity, but the complexes are progressively and irreversibly inactivated at lower lipid to protein ratios. Complexes containing more than the minimum lipid requirement show very similar temperature profiles of activity about 30 degrees C over a wide range of lipid to protein ratios, up to 1500:1. Spin-label studies indicate that, at lipid to protein ratios of less than about 30 lipids per ATPase, no DPL phase transition can be detected, but at all higher ratios, a phase transition occurs at about 41 degrees C. In all of these complexes there are breaks in the Arrhenius plots of ATPase activity at 27--32 degrees C and at 37.5--38.5 degrees C. Experiments with perturbing agents, such as cholesterol and benzyl alcohol which have well-defined effects on the DPL phase transition, indicate that these breaks in the Arrhenius plots of ATPase activity cannot be attributed to a depressed and broadened phase transition in the lipids near the protein molecules. These results are interpreted as evidence for a phospholipid annulus of at least 30 lipid molecules with interact directly with the ATPase and cannot undergo a phase transition at 41 degrees C. This structural interaction of the ATPase with the annular DPL molecules has a predominant effect in determining the form of the temperature-activity profiles. However, the perturbation of the DPL phase transition does not extend significantly beyond the annulus since a phase transition which starts at 41 degrees C can be detected as soon as extraannular lipid is present in the complexes. We suggest that it may be a general feature of membrane structure that penetrant membrane proteins interact with their immediate lipid environment so as to cause only a minimal perturbation of the lipid bilayer."}
{"id": "PMID:183812", "title": "Temperature-dependent 13C nuclear magnetic resonance studies of human serum low density lipoproteins.", "content": "The natural abundance 13C nuclear magnetic resonance (NMR) spectrum of human serum low density lipoproteins (LDL) shows significant temperature-dependent changes. These temperature-dependent spectra have been used to monitor changes in the organization of cholesterol esters within the LDL particle. Comparison with 13C NMR spectra of both cholesterol linoleate and an aqueous codispersion of cholesterol linoleate and egg phosphatidylcholine suggests that at low temperatures (10 degrees C), the cholesterol esters in LDL are organized in a smectic-like, liquid-crystalline arrangement. At temperatures above the order-disorder transition exhibited by the cholesterol esters of LDL, the cholesterol esters appear to be partially melted but still are motionally restricted compared with liquid cholesterol esters.", "contents": "Temperature-dependent 13C nuclear magnetic resonance studies of human serum low density lipoproteins. The natural abundance 13C nuclear magnetic resonance (NMR) spectrum of human serum low density lipoproteins (LDL) shows significant temperature-dependent changes. These temperature-dependent spectra have been used to monitor changes in the organization of cholesterol esters within the LDL particle. Comparison with 13C NMR spectra of both cholesterol linoleate and an aqueous codispersion of cholesterol linoleate and egg phosphatidylcholine suggests that at low temperatures (10 degrees C), the cholesterol esters in LDL are organized in a smectic-like, liquid-crystalline arrangement. At temperatures above the order-disorder transition exhibited by the cholesterol esters of LDL, the cholesterol esters appear to be partially melted but still are motionally restricted compared with liquid cholesterol esters."}
{"id": "PMID:183813", "title": "Limitation of reticulocyte transfer RNA in the translation of heterologous messenger RNAs.", "content": "The effect of various tRNAs on protein synthesis was investigated using a tRNA-dependent cell-free system from Ehrlich ascites cells. Ascites cell tRNA and rabbit liver tRNA were found to promote efficient translation of globin mRNA, oviduct mRNA, and encephalomycarditis (EMC) viral RNA. In contrast, reticulocyte tRNA participated efficiently only in the translation of globin mRNA; the translation  of oviduct mRNA AND EMC viral RNA in the presence of reticulocyte tRNA resulted in the synthesis of relatively few large mature proteins and the accumulation of discrete, smaller polypeptides. These results suggest that isoaccepting tRNA species required for the synthesis of ovalbumin and EMC viral protein (but not hemoglobin) are probably functionally absent in reticulocyte tRNA, causing a premature, nonrandom termination of synthesis of these proteins. This provides preliminary evidence that variations in tRNA populations, frequently observed between different cell types, are large enough to define and perhaps regulate the proteins that the cell is capable of synthesizing.", "contents": "Limitation of reticulocyte transfer RNA in the translation of heterologous messenger RNAs. The effect of various tRNAs on protein synthesis was investigated using a tRNA-dependent cell-free system from Ehrlich ascites cells. Ascites cell tRNA and rabbit liver tRNA were found to promote efficient translation of globin mRNA, oviduct mRNA, and encephalomycarditis (EMC) viral RNA. In contrast, reticulocyte tRNA participated efficiently only in the translation of globin mRNA; the translation  of oviduct mRNA AND EMC viral RNA in the presence of reticulocyte tRNA resulted in the synthesis of relatively few large mature proteins and the accumulation of discrete, smaller polypeptides. These results suggest that isoaccepting tRNA species required for the synthesis of ovalbumin and EMC viral protein (but not hemoglobin) are probably functionally absent in reticulocyte tRNA, causing a premature, nonrandom termination of synthesis of these proteins. This provides preliminary evidence that variations in tRNA populations, frequently observed between different cell types, are large enough to define and perhaps regulate the proteins that the cell is capable of synthesizing."}
{"id": "PMID:183814", "title": "The primary photoreactions in the complex cytochrome-P-890-P-760 (bacteriopheophytin760) of Chromatium minutissimum at low redox potentials.", "content": "Experimental evidence for electron transfer, photosensitized by bacteriochlorophyll, from cytochrome c to a pigment complex P-760 (involving bacteriopheophytin-760 and also bacteriochlorophyll-800) in the reaction centers of Chromatium minutissimum has been described. This photoreaction occurs between 77 and 293 degrees K at a redox potential of the medium between -250 and -530 mV. Photoreduction of P-760 is accompanied by development of a wide absorption band at 650 nm and of an EPR signal with g=2.0025+/-0.0005 and linewidth of 12.5+/-0.5 G, which are characteristic of the pigment radical anion. It is suggested that the photoreduction of P-760 occurs under the interaction of reduced cytochrome c with the reaction center state P+-890-P--760 which is induced by light. The existence of short-lived state P+-890-P--760 is indicated by the recombination luminescence with activation energy of 0.12 eV and t 1/2 less than or equal to 6 ns. This luminescence is exicted and emitted by bacteriochlorophyll and disappears when P-760 is reduced. At low redox potentials, the flash-induced absorbance changes related to the formation of the carotenoid triplet state with t 1/2 = 6 mus at 20 degreesC are observed. This state is not formed when P-760 is reduced at 293 and 160 degrees K. It is assumed that this state is formed from the reaction center state P+-890---760, which appears to be a primary product of light reaction in the bacterial reaction centers and which is probably identical with the state PF described in recent works.", "contents": "The primary photoreactions in the complex cytochrome-P-890-P-760 (bacteriopheophytin760) of Chromatium minutissimum at low redox potentials. Experimental evidence for electron transfer, photosensitized by bacteriochlorophyll, from cytochrome c to a pigment complex P-760 (involving bacteriopheophytin-760 and also bacteriochlorophyll-800) in the reaction centers of Chromatium minutissimum has been described. This photoreaction occurs between 77 and 293 degrees K at a redox potential of the medium between -250 and -530 mV. Photoreduction of P-760 is accompanied by development of a wide absorption band at 650 nm and of an EPR signal with g=2.0025+/-0.0005 and linewidth of 12.5+/-0.5 G, which are characteristic of the pigment radical anion. It is suggested that the photoreduction of P-760 occurs under the interaction of reduced cytochrome c with the reaction center state P+-890-P--760 which is induced by light. The existence of short-lived state P+-890-P--760 is indicated by the recombination luminescence with activation energy of 0.12 eV and t 1/2 less than or equal to 6 ns. This luminescence is exicted and emitted by bacteriochlorophyll and disappears when P-760 is reduced. At low redox potentials, the flash-induced absorbance changes related to the formation of the carotenoid triplet state with t 1/2 = 6 mus at 20 degreesC are observed. This state is not formed when P-760 is reduced at 293 and 160 degrees K. It is assumed that this state is formed from the reaction center state P+-890---760, which appears to be a primary product of light reaction in the bacterial reaction centers and which is probably identical with the state PF described in recent works."}
{"id": "PMID:183815", "title": "Thermodynamic properties of the reaction center of Rhodopseudomonas viridis. In vivo measurement of the reaction center bacteriochlorophyll-primary acceptor intermediary electron carrier.", "content": "The thermodynamic properties of redox components associated with the reaction center of Rhodopseudomonas viridis have been characterized with respect to their midpoint potentials and relationship with protons. In particular a midpoint potential for the intermediary electron carrier acting between the reaction center bacteriochlorophyll and the primary acceptor has been determined. The rationale for this measurement was that the light-induced triplet/biradical EPR signal would not be observed if this intermediate was chemically reduced before activation. The midpoint potential of the intermediary at pH 10.8 is about --400 mV (n=1).", "contents": "Thermodynamic properties of the reaction center of Rhodopseudomonas viridis. In vivo measurement of the reaction center bacteriochlorophyll-primary acceptor intermediary electron carrier. The thermodynamic properties of redox components associated with the reaction center of Rhodopseudomonas viridis have been characterized with respect to their midpoint potentials and relationship with protons. In particular a midpoint potential for the intermediary electron carrier acting between the reaction center bacteriochlorophyll and the primary acceptor has been determined. The rationale for this measurement was that the light-induced triplet/biradical EPR signal would not be observed if this intermediate was chemically reduced before activation. The midpoint potential of the intermediary at pH 10.8 is about --400 mV (n=1)."}
{"id": "PMID:183816", "title": "Kinetics of populating and depopulating of the components of the photoinduced triplet state of the photosynthetic bacteria Rhodospirillum rubrum, Rhodopseudomonas spheroides (wild type), and its mutant R-26 as measured by ESR in zero-field.", "content": "Optically detected ESR spectra in zero magnetic field of the triplet state of three photosynthetic bacteria are presented. The zero field splitting parameters [D] and [E] and the widths of the resonances show small but significant differences for the three bacteria. The resonance lines are inhomogeneously broadened as demonstrated by hole-burning experiments. The populating probabilities and depopulating rates for the triplet sublevels have been measured. The populating kinetics are very similar for the three bacteria. The depopulating rates are more than one order faster than those of chlorophyll a and chlorophyll b and of porphyrin model systems. The populating probability of the lowest level is about 6 times less, and the depopulating rate about 6 times slower, than for the upper levels, identifying this level as the level connected to the molecular z-axis perpendicular to the plane of the molecule. The relative populations of the triplet sublevels are almost equal in zero magnetic field.", "contents": "Kinetics of populating and depopulating of the components of the photoinduced triplet state of the photosynthetic bacteria Rhodospirillum rubrum, Rhodopseudomonas spheroides (wild type), and its mutant R-26 as measured by ESR in zero-field. Optically detected ESR spectra in zero magnetic field of the triplet state of three photosynthetic bacteria are presented. The zero field splitting parameters [D] and [E] and the widths of the resonances show small but significant differences for the three bacteria. The resonance lines are inhomogeneously broadened as demonstrated by hole-burning experiments. The populating probabilities and depopulating rates for the triplet sublevels have been measured. The populating kinetics are very similar for the three bacteria. The depopulating rates are more than one order faster than those of chlorophyll a and chlorophyll b and of porphyrin model systems. The populating probability of the lowest level is about 6 times less, and the depopulating rate about 6 times slower, than for the upper levels, identifying this level as the level connected to the molecular z-axis perpendicular to the plane of the molecule. The relative populations of the triplet sublevels are almost equal in zero magnetic field."}
{"id": "PMID:183817", "title": "Interactions between 125-I-labelled RNA from RNA tumor viruses and RNA of other sources.", "content": "Fragmented 125I-labelled RNA from RNA tumor viruses was hybridized to unlabelled RNA from cells, viruses, and homoribopolymers. The viral RNA interacted with all RNA tested, except for certain homoribopolymers. Complex formation with unlabelled RNA was verified by nuclease resistance, buoyant density measurements, and thermal stability in solutions of different ionic strength. The RNAase-resistant complex involved 20-30% of the sequences in the 125I-labelled viral RNA and formed preferentially with nuclear RNA of cells. 125I-labelled hemoglobin mRNA, 125I-labelled immunoglobulin light chain (lambda2) mRNA, or 125I-labelled viral RNA from encephalomyocarditis virus (EMC) dit not from RNAase-resistant complexes with unlabelled cellular RNA.", "contents": "Interactions between 125-I-labelled RNA from RNA tumor viruses and RNA of other sources. Fragmented 125I-labelled RNA from RNA tumor viruses was hybridized to unlabelled RNA from cells, viruses, and homoribopolymers. The viral RNA interacted with all RNA tested, except for certain homoribopolymers. Complex formation with unlabelled RNA was verified by nuclease resistance, buoyant density measurements, and thermal stability in solutions of different ionic strength. The RNAase-resistant complex involved 20-30% of the sequences in the 125I-labelled viral RNA and formed preferentially with nuclear RNA of cells. 125I-labelled hemoglobin mRNA, 125I-labelled immunoglobulin light chain (lambda2) mRNA, or 125I-labelled viral RNA from encephalomyocarditis virus (EMC) dit not from RNAase-resistant complexes with unlabelled cellular RNA."}
{"id": "PMID:183818", "title": "Efficeint transcription of RNA into DNA by avian sarcoma virus polymerase.", "content": "The DNAase digestion end-product of calf thymus DNA contains oligonucleotides that will function as primers for the efficient transcription into DNA of many naturally-occurring RNA's by purified avian sarcoma virus RNA-directed DNA polymerase. The labeled DNA transcripts so obtained are valuable as probes for molecular hybridization studies. Typical applications of the method include the efficient transcription into DNA of 18 and 28 S rRNA as well as the RNA's of avian sarcoma virus, polio virus, influenza virus, satellite tobacco necrosis virus and tobacco mosaic virus. In addition, when these primers are added to avian sarcoma virus particles that have been partially-disrupted with non-ionic detergent there is 6-fold stimulation of the endogenous RNA-directed DNA synthesis.", "contents": "Efficeint transcription of RNA into DNA by avian sarcoma virus polymerase. The DNAase digestion end-product of calf thymus DNA contains oligonucleotides that will function as primers for the efficient transcription into DNA of many naturally-occurring RNA's by purified avian sarcoma virus RNA-directed DNA polymerase. The labeled DNA transcripts so obtained are valuable as probes for molecular hybridization studies. Typical applications of the method include the efficient transcription into DNA of 18 and 28 S rRNA as well as the RNA's of avian sarcoma virus, polio virus, influenza virus, satellite tobacco necrosis virus and tobacco mosaic virus. In addition, when these primers are added to avian sarcoma virus particles that have been partially-disrupted with non-ionic detergent there is 6-fold stimulation of the endogenous RNA-directed DNA synthesis."}
{"id": "PMID:183819", "title": "Effect of cyclic AMP on chromatin-bound protein kinases in WI-38 fibroblasts stimulated to proliferate.", "content": "When resting confluent monolayers of WI-38 fibroblasts are stimulated to proliferate by serum, DNA synthesis begins to increase between 15-18 h after stimulation. Chromatin-bound protein kinase activity increases in stimulated cells within 1 h after the nutritional change, concomitant with an increase in the template activity of nuclear chromatin. Addition of dibutyryl 3' : 5'-cyclic adenosine monophosphate (dibutyryl cyclic) AMP to the stimulating medium inhibits the entrance of cells into S phase, but only if dibutyryl cyclic AMP (5-10(-4) M) is added before the onset of DNA synthesis. The increases in chromatin template activity and in the chromatin-bound kinase activity are not inhibited by dibutyryl cyclic AMP in the early hours after stimulation, but are completely inhibited after the 5th hour from the nutritional change. This seems to indicate that in stimulated WI-38 cells, dibutyryl cyclic AMP exerts its inhibitory action somewhere between 5 and 12 h after stimulation. A number of protein kinase activities were extracted from chromatin with 0.3 M NaCl and partially resolved on a phosphocellulose column. Two distinct peaks of protein kinase activity appeared to be markedly increased in WI-38 cells 6 h after serum stimulation. Both peaks of increased activity were inhibited by dibutyryl cyclic AMP in vivo. Adenosine, sodium butyrate and adenosine 5'-monophosphate (AMP) do not inhibit the increase in DNA synthesis nor the increase in protein kinase activity. The results suggest that stimulation of cell proliferation in confluent monolayers of WI-38 cells causes an increase (or the new appearance) of certain chromatin-bound protein kinases, and that this increase is inhibited by cyclic AMP in vivo.", "contents": "Effect of cyclic AMP on chromatin-bound protein kinases in WI-38 fibroblasts stimulated to proliferate. When resting confluent monolayers of WI-38 fibroblasts are stimulated to proliferate by serum, DNA synthesis begins to increase between 15-18 h after stimulation. Chromatin-bound protein kinase activity increases in stimulated cells within 1 h after the nutritional change, concomitant with an increase in the template activity of nuclear chromatin. Addition of dibutyryl 3' : 5'-cyclic adenosine monophosphate (dibutyryl cyclic) AMP to the stimulating medium inhibits the entrance of cells into S phase, but only if dibutyryl cyclic AMP (5-10(-4) M) is added before the onset of DNA synthesis. The increases in chromatin template activity and in the chromatin-bound kinase activity are not inhibited by dibutyryl cyclic AMP in the early hours after stimulation, but are completely inhibited after the 5th hour from the nutritional change. This seems to indicate that in stimulated WI-38 cells, dibutyryl cyclic AMP exerts its inhibitory action somewhere between 5 and 12 h after stimulation. A number of protein kinase activities were extracted from chromatin with 0.3 M NaCl and partially resolved on a phosphocellulose column. Two distinct peaks of protein kinase activity appeared to be markedly increased in WI-38 cells 6 h after serum stimulation. Both peaks of increased activity were inhibited by dibutyryl cyclic AMP in vivo. Adenosine, sodium butyrate and adenosine 5'-monophosphate (AMP) do not inhibit the increase in DNA synthesis nor the increase in protein kinase activity. The results suggest that stimulation of cell proliferation in confluent monolayers of WI-38 cells causes an increase (or the new appearance) of certain chromatin-bound protein kinases, and that this increase is inhibited by cyclic AMP in vivo."}
{"id": "PMID:183820", "title": "Laser Raman spectroscopy of lipid-protein systems. Differences in the effect of intrinsic and extrinsic proteins on the phosphatidylcholine Raman spectrum.", "content": "Laser Raman spectroscopy is used to examine the interactions of intrinsic and extrinsic proteins with the lipid layer structure. The interactions of cytochrome c and cytochrome c oxidase with lipids have been well established by others using a variety of techniques. Cytochrome c is thought to act as an extrinsic membrane protein while cytochrome c oxidase is thought to act as an intrinsic membrane protein. The lipid-cytochrome c and lipid cytochrome c oxidase systems are used to assist in interpreting the spectral changes due to extrinsic and intrinsic protein interactions. The two types of proteins examined produced differential changes in the lipid hydrocarbon C-H stretch Raman modes for both dimyristoyl and dipalmitoyl phosphatidylcholine. The plasma proteins albumin and fibrinogen were also found to differentially affect the lipid hydrocarbon C-H stretch Raman nodes. These proteins appear to interact with lipids in an extrinsic manner different from that of cytochrome c.", "contents": "Laser Raman spectroscopy of lipid-protein systems. Differences in the effect of intrinsic and extrinsic proteins on the phosphatidylcholine Raman spectrum. Laser Raman spectroscopy is used to examine the interactions of intrinsic and extrinsic proteins with the lipid layer structure. The interactions of cytochrome c and cytochrome c oxidase with lipids have been well established by others using a variety of techniques. Cytochrome c is thought to act as an extrinsic membrane protein while cytochrome c oxidase is thought to act as an intrinsic membrane protein. The lipid-cytochrome c and lipid cytochrome c oxidase systems are used to assist in interpreting the spectral changes due to extrinsic and intrinsic protein interactions. The two types of proteins examined produced differential changes in the lipid hydrocarbon C-H stretch Raman modes for both dimyristoyl and dipalmitoyl phosphatidylcholine. The plasma proteins albumin and fibrinogen were also found to differentially affect the lipid hydrocarbon C-H stretch Raman nodes. These proteins appear to interact with lipids in an extrinsic manner different from that of cytochrome c."}
{"id": "PMID:183821", "title": "The relationship between environmental temperature, cell growth and the fluidity and physical state of the membrane lipids in Bacillus stearothermophilus.", "content": "A definite and characteristic relationship exists between growth temperature, fatty acid composition and the fluidity and physical state of the membrane lipids in wild type Bacillus stearothermophilus. As the environmental temperature is increased, the proportion of saturated fatty acids found in the membrane lipids is also markedly increased with a concomitant decrease in the proportion of unsaturated and branched chain fatty acids. The temperature range over which the gel to liquid-crystalline membrane lipid phase transition occurs is thereby shifted such that the upper boundary of this transition always lies near (and usually below) the temperature of growth. This organism thus possesses an effective and sensitive homeoviscous adaptation mechanism which maintains a relatively constant degree of membrane lipid fluidity over a wide range of environmental temperatures. A mutant of B. stearothermophilus which has lost the ability to increase the proportion of relatively high melting fatty acids in the membrane lipids, and thereby increase the phase transition temperature in response to increases in environmental temperature, is also unable to grow at higher temperatures. An effective homeoviscous regulatory mechanism thus appears to extend the growth temperature range of the wild type organism and may be an essential feature of adaptation to temperature extremes. Over most of their growth temperature ranges the membrane lipids of wild type and temperature-sensitive B. stearothermophilus cells exist entirely or nearly entirely in the liquid-crystalline state. Also, the temperature-sensitive mutant is capable of growth at temperatures well above those at which the membrane lipid gel to liquid-crystalline phase transition is completed. Therefore, although other evidence suggests the existence of an upper limit on the degree of membrane fluidity compatible with cell growth, the phase transition is completed. Therefore, although other evidence suggests the existence of an upper limit on the degree of membrane fluidity compatible with cell growth, the phase transition upper boundary itself does not directly determine the maximum growth temperature of this organism. Similarly, the lower boundary does not determine the minimum growth temperature, since cell growth ceases at a temperature at which most of the membrane lipid still exists in a fluid state. These observations do not support the suggestion made in an earlier study, which utilized electron spin resonance spectroscopy to monitor membrane lipid lateral phase separations, that the minimum and maximum growth temperatures of this organism might directly be determined by the solid-fluid membrane lipid phase transition boundaries. Evidence is presented here that the electron spin resonance techniques used previously did not in fact detect the gel to liquid-crystalline phase transition of the bulk membrane lipids, which, however, can be reliably measured by differential thermal analysis.", "contents": "The relationship between environmental temperature, cell growth and the fluidity and physical state of the membrane lipids in Bacillus stearothermophilus. A definite and characteristic relationship exists between growth temperature, fatty acid composition and the fluidity and physical state of the membrane lipids in wild type Bacillus stearothermophilus. As the environmental temperature is increased, the proportion of saturated fatty acids found in the membrane lipids is also markedly increased with a concomitant decrease in the proportion of unsaturated and branched chain fatty acids. The temperature range over which the gel to liquid-crystalline membrane lipid phase transition occurs is thereby shifted such that the upper boundary of this transition always lies near (and usually below) the temperature of growth. This organism thus possesses an effective and sensitive homeoviscous adaptation mechanism which maintains a relatively constant degree of membrane lipid fluidity over a wide range of environmental temperatures. A mutant of B. stearothermophilus which has lost the ability to increase the proportion of relatively high melting fatty acids in the membrane lipids, and thereby increase the phase transition temperature in response to increases in environmental temperature, is also unable to grow at higher temperatures. An effective homeoviscous regulatory mechanism thus appears to extend the growth temperature range of the wild type organism and may be an essential feature of adaptation to temperature extremes. Over most of their growth temperature ranges the membrane lipids of wild type and temperature-sensitive B. stearothermophilus cells exist entirely or nearly entirely in the liquid-crystalline state. Also, the temperature-sensitive mutant is capable of growth at temperatures well above those at which the membrane lipid gel to liquid-crystalline phase transition is completed. Therefore, although other evidence suggests the existence of an upper limit on the degree of membrane fluidity compatible with cell growth, the phase transition is completed. Therefore, although other evidence suggests the existence of an upper limit on the degree of membrane fluidity compatible with cell growth, the phase transition upper boundary itself does not directly determine the maximum growth temperature of this organism. Similarly, the lower boundary does not determine the minimum growth temperature, since cell growth ceases at a temperature at which most of the membrane lipid still exists in a fluid state. These observations do not support the suggestion made in an earlier study, which utilized electron spin resonance spectroscopy to monitor membrane lipid lateral phase separations, that the minimum and maximum growth temperatures of this organism might directly be determined by the solid-fluid membrane lipid phase transition boundaries. Evidence is presented here that the electron spin resonance techniques used previously did not in fact detect the gel to liquid-crystalline phase transition of the bulk membrane lipids, which, however, can be reliably measured by differential thermal analysis."}
{"id": "PMID:183822", "title": "Characterization, enzymatic and lectin properties of isolated membranes from Phaseolus aureus.", "content": "Cellular membranes were prepared from the non-extending part of dark grown hypocotyls of Phaseolus aureus. The relative effectiveness of continuous and discontinuous sucrose gradient centrifugation for the separation of membranes was investigated. Characteristic densities of membranes were determined by the localization of enzyme activities on continuous sucrose gradients: NADH-cytochrome c-reductase for endoplasmic reticulum, beta-1-3-glucan synthetase for plasma-membrane and IDPase for dictyosomes. The difficulties involved in the application of ATPase and IDPase as specific membrane markers are discussed. Negative staining of isolated fractions indicated that intact dictyosomes could be prepared from this tissue without the use of chemical fixatives in the homogenization medium. Extraction of isolated membranes showed that carbohydrate-binding proteins (lectins) were present both in an easily removable and in a more strongly bound form. In vivo incorporation of D-[U-14C]glucose and subsequent isolation and solubilization of the different membranes showed that sugar-containing polymers could be released without hydrolytic techniques and were present in the equivalent extracts that exhibited lectin activity. The possibility of lectin-polysaccharide complexes in endoplasmic reticulum and dictyosomes and their involvement in the synthesis and transport of secretory substances by the membranes is discussed.", "contents": "Characterization, enzymatic and lectin properties of isolated membranes from Phaseolus aureus. Cellular membranes were prepared from the non-extending part of dark grown hypocotyls of Phaseolus aureus. The relative effectiveness of continuous and discontinuous sucrose gradient centrifugation for the separation of membranes was investigated. Characteristic densities of membranes were determined by the localization of enzyme activities on continuous sucrose gradients: NADH-cytochrome c-reductase for endoplasmic reticulum, beta-1-3-glucan synthetase for plasma-membrane and IDPase for dictyosomes. The difficulties involved in the application of ATPase and IDPase as specific membrane markers are discussed. Negative staining of isolated fractions indicated that intact dictyosomes could be prepared from this tissue without the use of chemical fixatives in the homogenization medium. Extraction of isolated membranes showed that carbohydrate-binding proteins (lectins) were present both in an easily removable and in a more strongly bound form. In vivo incorporation of D-[U-14C]glucose and subsequent isolation and solubilization of the different membranes showed that sugar-containing polymers could be released without hydrolytic techniques and were present in the equivalent extracts that exhibited lectin activity. The possibility of lectin-polysaccharide complexes in endoplasmic reticulum and dictyosomes and their involvement in the synthesis and transport of secretory substances by the membranes is discussed."}
{"id": "PMID:183823", "title": "Stimulation of the biosynthesis of membrane glycoproteins from Zajdela ascites hepatoma cells by Robinia lectin.", "content": "Membrane glycoprotein biosynthesis of ascites hepatoma cells is followed by [14C]glucosamine and [3H]leucine incorporation into cells in culture. The rate of incorporation is strongly increased by the addition of Robinia lectin in culture medium. Labeled glycoproteins are released from lectin stimulated and non-stimulated cells by trypsin digestion. Studies of labeled trypsinates on sodium dodecyl sulfate gel electrophoresis and Sephadex G-200 filtration exhibit two fractions both labeled with [14C]glucosamine and [3H]leucine and having different molecular weights, one over 200000 and the other about 2000. Identical results are obtained when external membrane glycoproteins are solubilized by sodium deoxycholate. Comparison of surface glycoproteins isolated by trypsinization from control cells labeled with [3H]-glucosamine and from lectin stimulated cells labeled with [14C]glucosamine displays no significant qualitative differences between glycoprotein fractions released from both cell groups.", "contents": "Stimulation of the biosynthesis of membrane glycoproteins from Zajdela ascites hepatoma cells by Robinia lectin. Membrane glycoprotein biosynthesis of ascites hepatoma cells is followed by [14C]glucosamine and [3H]leucine incorporation into cells in culture. The rate of incorporation is strongly increased by the addition of Robinia lectin in culture medium. Labeled glycoproteins are released from lectin stimulated and non-stimulated cells by trypsin digestion. Studies of labeled trypsinates on sodium dodecyl sulfate gel electrophoresis and Sephadex G-200 filtration exhibit two fractions both labeled with [14C]glucosamine and [3H]leucine and having different molecular weights, one over 200000 and the other about 2000. Identical results are obtained when external membrane glycoproteins are solubilized by sodium deoxycholate. Comparison of surface glycoproteins isolated by trypsinization from control cells labeled with [3H]-glucosamine and from lectin stimulated cells labeled with [14C]glucosamine displays no significant qualitative differences between glycoprotein fractions released from both cell groups."}
{"id": "PMID:183824", "title": "Differential inactivation of the \"L\" and \"Ly+\" amino acid transport systems by a sulfhydryl reagent and a photo-affinity probe.", "content": "Using a substrate-stimulated amino acid efflux system, it has been shown that the \"Ly+\" and \"L\" amino acid transport systems of mouse embryo cells in culture are differentially inhibited by parachloromercuribenzene sulfonate (PCMB-S) and the photoaffinity probe 4-fluoro-3-nitrophenylazide (FNPA). Three types of evidence support the conclusion that these transport systems are mediated by separate carrier proteins. (1) The specificity of substrate-stimulated efflux is high for each system; (2) PCMB-S inhibits L-phenylalanine and L-leucine stimulated L-[3H]phenylalanine efflux with no effect on L-lysine stimulated L-[3H]lysine efflux, and (3) the photo-affinity probe FNPA inhibits L-lysine efflux with little effect on the L-phenylalanine-stimulated efflux.", "contents": "Differential inactivation of the \"L\" and \"Ly+\" amino acid transport systems by a sulfhydryl reagent and a photo-affinity probe. Using a substrate-stimulated amino acid efflux system, it has been shown that the \"Ly+\" and \"L\" amino acid transport systems of mouse embryo cells in culture are differentially inhibited by parachloromercuribenzene sulfonate (PCMB-S) and the photoaffinity probe 4-fluoro-3-nitrophenylazide (FNPA). Three types of evidence support the conclusion that these transport systems are mediated by separate carrier proteins. (1) The specificity of substrate-stimulated efflux is high for each system; (2) PCMB-S inhibits L-phenylalanine and L-leucine stimulated L-[3H]phenylalanine efflux with no effect on L-lysine stimulated L-[3H]lysine efflux, and (3) the photo-affinity probe FNPA inhibits L-lysine efflux with little effect on the L-phenylalanine-stimulated efflux."}
{"id": "PMID:183825", "title": "Membrane lipid acyl group alterations in cells infected with a temperature-conditional mutant of Rous sarcoma virus.", "content": "The increased percentage of oleic acid and decreased percentage of arachidonic acid which occurs in the lipids of chicken embryo fibroblasts transformed by Rous sarcoma virus was shown to be transformation specific rather than a consequence of virus infection. Cells infected with a temperature conditional mutant of Rous sarcoma virus (RSV-T5) had a normal type fatty acid composition when held at the restrictive temperature of 41 degrees C, but had a transformed type fatty acid composition when held at the permissive temperature of 36 degrees C. However, these acyl group changes occurred slowly in the course of transformation, suggesting that they are not a primary event in the genesis of the transformed phenotype.", "contents": "Membrane lipid acyl group alterations in cells infected with a temperature-conditional mutant of Rous sarcoma virus. The increased percentage of oleic acid and decreased percentage of arachidonic acid which occurs in the lipids of chicken embryo fibroblasts transformed by Rous sarcoma virus was shown to be transformation specific rather than a consequence of virus infection. Cells infected with a temperature conditional mutant of Rous sarcoma virus (RSV-T5) had a normal type fatty acid composition when held at the restrictive temperature of 41 degrees C, but had a transformed type fatty acid composition when held at the permissive temperature of 36 degrees C. However, these acyl group changes occurred slowly in the course of transformation, suggesting that they are not a primary event in the genesis of the transformed phenotype."}
{"id": "PMID:183826", "title": "The effect of hypoxia on collagen synthesis in cultured 3T6 fibroblasts and its relationship to the mode of action of ascorbate.", "content": "When exposed to low oxygen tension, in the absence of added ascorbic acid 3T6 mouse fibroblast cultures in late log phase respond by increased lactate production and increased hydroxylation of proline in nascent collagen, which is paralleled by an increase in prolyl hydroxylase activity. After 6 h recovery from the anoxic stimulus, however, cultures still yield more prolyl hydroxylase than controls, but the effect on hydroxylation of nascent collagen has disappeared. These observations help to dissect the dual role of ascorbate which can stimulate hydroxylation both by increasing the amount of active enzyme and by a cofactor-like role; in addition, these observations may be relevant to wound healing.", "contents": "The effect of hypoxia on collagen synthesis in cultured 3T6 fibroblasts and its relationship to the mode of action of ascorbate. When exposed to low oxygen tension, in the absence of added ascorbic acid 3T6 mouse fibroblast cultures in late log phase respond by increased lactate production and increased hydroxylation of proline in nascent collagen, which is paralleled by an increase in prolyl hydroxylase activity. After 6 h recovery from the anoxic stimulus, however, cultures still yield more prolyl hydroxylase than controls, but the effect on hydroxylation of nascent collagen has disappeared. These observations help to dissect the dual role of ascorbate which can stimulate hydroxylation both by increasing the amount of active enzyme and by a cofactor-like role; in addition, these observations may be relevant to wound healing."}
{"id": "PMID:183827", "title": "Attenuation of epinephrine-induced increase in liver cyclic AMP by endogeneous insulin in vivo.", "content": "1. Epinephrine-induced increase in rat liver cyclic AMP in vivo was potentiated when the circulating insulin was suppressed by injection of anti-insulin serum or by induction of diabetes. Consequently, phosphorylase was activated, glycogen synthetase was inactivated and glycogen accumulation induced by glucose load was prevented by epinephrine in the insulin-deficient rats to a much larger extent than in normal rats. 2. Insulin lack was effective in potentiating epinephrine-induced increase in liver and muscule cyclic AMP even after the treatment of rats with theophylline; the potentiation could not be solely accounted for by the inhibition of cyclic AMP phosphodiesterase. Thus, it is likely that insulin lack enhaces epinephrine activation of adenylate cyclase. 3. Unlike epinephrine, glucagon increased liver cyclic AMP to essentially the same extent whether the rat was treated with anti-insulin serum or not. 4. Based on the difference in dose-response curves between normal and insulin-deficient rats, a possibility is discussed that there are two adenylate cylase in the liver with higher and lower affinities for epinephrine and that circulating insulin blocks the high affinity enzyme selectively.", "contents": "Attenuation of epinephrine-induced increase in liver cyclic AMP by endogeneous insulin in vivo. 1. Epinephrine-induced increase in rat liver cyclic AMP in vivo was potentiated when the circulating insulin was suppressed by injection of anti-insulin serum or by induction of diabetes. Consequently, phosphorylase was activated, glycogen synthetase was inactivated and glycogen accumulation induced by glucose load was prevented by epinephrine in the insulin-deficient rats to a much larger extent than in normal rats. 2. Insulin lack was effective in potentiating epinephrine-induced increase in liver and muscule cyclic AMP even after the treatment of rats with theophylline; the potentiation could not be solely accounted for by the inhibition of cyclic AMP phosphodiesterase. Thus, it is likely that insulin lack enhaces epinephrine activation of adenylate cyclase. 3. Unlike epinephrine, glucagon increased liver cyclic AMP to essentially the same extent whether the rat was treated with anti-insulin serum or not. 4. Based on the difference in dose-response curves between normal and insulin-deficient rats, a possibility is discussed that there are two adenylate cylase in the liver with higher and lower affinities for epinephrine and that circulating insulin blocks the high affinity enzyme selectively."}
{"id": "PMID:183828", "title": "Cyclic AMP and growth of Ehrlich ascites tumor cells. Lack of cyclic AMP elevation in nutritionally deprived cells and mechanism of retardation of growth by dibutryl cyclic AMP.", "content": "Cyclic AMP levels in Ehrlich ascites tumor cells changed little after deprivation of cells of essential nutrients, serum, glucose and amino acids, deprival of each of which leads to marked inhibition of growth and protein synthesis. Cyclic AMP levels also changed little after the addition of these nutrients to deprived cells. Thus cyclic AMP is not likely to be the intracellular mediator for growth regulation by these three nutrients. Elevation of cyclic AMP levels for short periods by exposure of cells to choleratoxin or theophylline produced only slight changes in parameters of protein synthesis (polyribosome pattern and rate of [3H]leucine incorporation). An exposure for 1 day to dibutyryl cyclic AMP did not inhibit cell growth. However, prolonged exposure to dibutyryl cyclic AMP inhibited the multiplication of Ehrlich  ascites cells both in suspension and in stationary cultures. No morphological effects were evident in the former; in the latter, cells attached firmly to the substratum and formed elongated cytoplasmic processes. Inhibition of cell multiplication by dibutyryl cyclic AMP was related to cell density and to serum concentration. Cells in dibutyryl cyclic AMP-containing media plated at low cell densities multiplied as rapidly as control cells. The final densities cells reached were determined by the serum concentration; in dibutyryl cyclic AMP-containing media these densities were about one-half those of respective control cells. Limitation of cell multiplication by dibutyryl cyclic AMP was reversed by the addition of serum, by resuspending cells at lower densities, or by resuspending cells in media without dibutyryl cyclic AMP. These findings suggested that dibutyryl cyclic AMP may affect the utilization of serum factors by cells. Dibutyryl cyclic AMP did not inactivate serum factors and did not change the rate at which cells depleted the growth medium of serum factors. Dibutyryl cyclic AMP may limit cell multiplication by increasing the cellular requirement for serum factors.", "contents": "Cyclic AMP and growth of Ehrlich ascites tumor cells. Lack of cyclic AMP elevation in nutritionally deprived cells and mechanism of retardation of growth by dibutryl cyclic AMP. Cyclic AMP levels in Ehrlich ascites tumor cells changed little after deprivation of cells of essential nutrients, serum, glucose and amino acids, deprival of each of which leads to marked inhibition of growth and protein synthesis. Cyclic AMP levels also changed little after the addition of these nutrients to deprived cells. Thus cyclic AMP is not likely to be the intracellular mediator for growth regulation by these three nutrients. Elevation of cyclic AMP levels for short periods by exposure of cells to choleratoxin or theophylline produced only slight changes in parameters of protein synthesis (polyribosome pattern and rate of [3H]leucine incorporation). An exposure for 1 day to dibutyryl cyclic AMP did not inhibit cell growth. However, prolonged exposure to dibutyryl cyclic AMP inhibited the multiplication of Ehrlich  ascites cells both in suspension and in stationary cultures. No morphological effects were evident in the former; in the latter, cells attached firmly to the substratum and formed elongated cytoplasmic processes. Inhibition of cell multiplication by dibutyryl cyclic AMP was related to cell density and to serum concentration. Cells in dibutyryl cyclic AMP-containing media plated at low cell densities multiplied as rapidly as control cells. The final densities cells reached were determined by the serum concentration; in dibutyryl cyclic AMP-containing media these densities were about one-half those of respective control cells. Limitation of cell multiplication by dibutyryl cyclic AMP was reversed by the addition of serum, by resuspending cells at lower densities, or by resuspending cells in media without dibutyryl cyclic AMP. These findings suggested that dibutyryl cyclic AMP may affect the utilization of serum factors by cells. Dibutyryl cyclic AMP did not inactivate serum factors and did not change the rate at which cells depleted the growth medium of serum factors. Dibutyryl cyclic AMP may limit cell multiplication by increasing the cellular requirement for serum factors."}
{"id": "PMID:183829", "title": "Ontogenetic changes in levels of phosphodiesterase for adenosine 3':5'-monophosphate and glucosine 3':5'-monophosphate in the lung, brain and heart from guinea pigs.", "content": "Changes in tissue levels of the low Km phosphodiesterase for adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclc GMP) in the lung, liver, heart and brain from developing guinea pigs were studied. It was found that the contents of the soluble (cytosol) phosphodiesterase for both cyclic AMP and cyclic GMP were higher in the lung from the fetus than from the neonate and adult. The ontogenetic changes seen in the liver were qualitatively similar to thos in the lung with respect to cyclic GMP hydrolysis, while a reversed pattern of change was noted in the brain. The level of cyclic AMP phosphodiesterase was highest in the fetal heart. Throughout the fetal stage, the levels of the enzyme for cyclic GMP hydrolysis were higher than those for cyclic AMP in the lung. At or around birth, a reversal in the relative levels of the two enzymes took place; two days after birth, the level of the enzyme for cyclic AMP was 2-3times higher than thos for cyclic GMP. Kinetic analysis showed that phohphodiesterases from extracts of the lung from all developmental stages of guinea pigs had the same Km (2.6 muM) for cyclic AMP and the same Km (6.6 muM) for cyclic GMP. The relative values of V, based on assays using the same amount of enzyme protein, in decreasing order, were fetus greater than neonate greater than adult. The present findings suggest that metabolism of the two cyclic nucleotides may be closely related to developmental processes of the tissues. Moreover, the actions involving cyclic GMP may be more predominent in the fetal lung and adult brain.", "contents": "Ontogenetic changes in levels of phosphodiesterase for adenosine 3':5'-monophosphate and glucosine 3':5'-monophosphate in the lung, brain and heart from guinea pigs. Changes in tissue levels of the low Km phosphodiesterase for adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclc GMP) in the lung, liver, heart and brain from developing guinea pigs were studied. It was found that the contents of the soluble (cytosol) phosphodiesterase for both cyclic AMP and cyclic GMP were higher in the lung from the fetus than from the neonate and adult. The ontogenetic changes seen in the liver were qualitatively similar to thos in the lung with respect to cyclic GMP hydrolysis, while a reversed pattern of change was noted in the brain. The level of cyclic AMP phosphodiesterase was highest in the fetal heart. Throughout the fetal stage, the levels of the enzyme for cyclic GMP hydrolysis were higher than those for cyclic AMP in the lung. At or around birth, a reversal in the relative levels of the two enzymes took place; two days after birth, the level of the enzyme for cyclic AMP was 2-3times higher than thos for cyclic GMP. Kinetic analysis showed that phohphodiesterases from extracts of the lung from all developmental stages of guinea pigs had the same Km (2.6 muM) for cyclic AMP and the same Km (6.6 muM) for cyclic GMP. The relative values of V, based on assays using the same amount of enzyme protein, in decreasing order, were fetus greater than neonate greater than adult. The present findings suggest that metabolism of the two cyclic nucleotides may be closely related to developmental processes of the tissues. Moreover, the actions involving cyclic GMP may be more predominent in the fetal lung and adult brain."}
{"id": "PMID:183830", "title": "Antagonism of the prostaglandin endoperoxide imhibition of hormone-stimulated adenylate cyclase by guanosine triphosphate and 5'-guanylyl-imidodiphosphate.", "content": "The prostaglandin endoperoxide prostaglandin H2 (15-hydroxy-9alpha, 11alpha-peroxidoprosta-5,13-dienoic acid) inhibits basal and hormone-stimulated adenylate cyclase in fat cell ghosts. This inhibition by prostaglandin H2 has been found to be antagonized by GTP and Gpp(NH)p. Dose response studies have shown GTP and Gpp(nh)p to be maximally effective at 3.3 muM, the lowest concentration tested. Although the system is exceedingly sensitive to modulation by GTP or Gpp(NH)p UTP, CTP, GMP, and cyclic GMP did not antagonize the antihormone activity of prostaglandin H2. Kinetic studies indicate that the GTP or Gpp(NH)p antagonism of prostaglandin H2 is observable on initial rates of cyclic AMP synthesis, and persists throughout the adenylate cyclase measurements. Preincubation of fat cell ghosts with GTP followed by washing and resuspension results in a prostaglandin H2-sensitive adenylate cyclase system. However, the same preincubation experiment with Gpp(NH)p produces an irreversible antagonism of the prostaglandin H2 inhibition of hormone-stimulated adenylate cyclase. It is suggested that prostaglandin H2 stabilizes the fat cell adenylate cyclase system in a state that is resistant to hormone stimulation, and GTP or Gpp(NH)p overcome this stabilization.", "contents": "Antagonism of the prostaglandin endoperoxide imhibition of hormone-stimulated adenylate cyclase by guanosine triphosphate and 5'-guanylyl-imidodiphosphate. The prostaglandin endoperoxide prostaglandin H2 (15-hydroxy-9alpha, 11alpha-peroxidoprosta-5,13-dienoic acid) inhibits basal and hormone-stimulated adenylate cyclase in fat cell ghosts. This inhibition by prostaglandin H2 has been found to be antagonized by GTP and Gpp(NH)p. Dose response studies have shown GTP and Gpp(nh)p to be maximally effective at 3.3 muM, the lowest concentration tested. Although the system is exceedingly sensitive to modulation by GTP or Gpp(NH)p UTP, CTP, GMP, and cyclic GMP did not antagonize the antihormone activity of prostaglandin H2. Kinetic studies indicate that the GTP or Gpp(NH)p antagonism of prostaglandin H2 is observable on initial rates of cyclic AMP synthesis, and persists throughout the adenylate cyclase measurements. Preincubation of fat cell ghosts with GTP followed by washing and resuspension results in a prostaglandin H2-sensitive adenylate cyclase system. However, the same preincubation experiment with Gpp(NH)p produces an irreversible antagonism of the prostaglandin H2 inhibition of hormone-stimulated adenylate cyclase. It is suggested that prostaglandin H2 stabilizes the fat cell adenylate cyclase system in a state that is resistant to hormone stimulation, and GTP or Gpp(NH)p overcome this stabilization."}
{"id": "PMID:183831", "title": "[The effects of adrenalectomy and of hydrocortisone administration on adenylate cyclase activity in rabbit adipose cells (author's transl)].", "content": "Adenylate cyclase activity in rabbit adipocyte plasma membranes was studied with special reference to the effects of adrenalectomy and administration of cortisol in vivo. Adrenalectomy was accompanied by an increase in adenylate cyclase activity during basal conditions; cortisol (5 mg/kg body wt., intramuscularly) partly prevents this effect of adrenalectomy. The response of adenylate cyclase to corticotropin, epinephrine and norepinephrine stimulation was higher in the adrenalectomized rabbit than in the sham operated animal. Our in vitro results were in agreement with the striking fat mobilization observed in rabbit plasma after adrenalectomy and with the hypolipemic effects of cortisol we had previously observed in both normal and adrenalectomized rabbit.", "contents": "[The effects of adrenalectomy and of hydrocortisone administration on adenylate cyclase activity in rabbit adipose cells (author's transl)]. Adenylate cyclase activity in rabbit adipocyte plasma membranes was studied with special reference to the effects of adrenalectomy and administration of cortisol in vivo. Adrenalectomy was accompanied by an increase in adenylate cyclase activity during basal conditions; cortisol (5 mg/kg body wt., intramuscularly) partly prevents this effect of adrenalectomy. The response of adenylate cyclase to corticotropin, epinephrine and norepinephrine stimulation was higher in the adrenalectomized rabbit than in the sham operated animal. Our in vitro results were in agreement with the striking fat mobilization observed in rabbit plasma after adrenalectomy and with the hypolipemic effects of cortisol we had previously observed in both normal and adrenalectomized rabbit."}
{"id": "PMID:183832", "title": "Production of collagenase by mouse peritoneal macrophages in vitro. Characterization of sites of cleavage of tropocollagen.", "content": "Macrophages from mineral oil-stimulated mice produce collagenase at a constant rate over several days in culture. Phagocytosis of latex does not increase production of enzyme. Gel electrophoretic and electron microscopic analyses indicate that the specificity of the macrophage enzyme is similar to that of other previously characterized mammalian collagenases.", "contents": "Production of collagenase by mouse peritoneal macrophages in vitro. Characterization of sites of cleavage of tropocollagen. Macrophages from mineral oil-stimulated mice produce collagenase at a constant rate over several days in culture. Phagocytosis of latex does not increase production of enzyme. Gel electrophoretic and electron microscopic analyses indicate that the specificity of the macrophage enzyme is similar to that of other previously characterized mammalian collagenases."}
{"id": "PMID:183833", "title": "Repair replication of DNA in the intact animal following treatment with dimethylnitrosamine and with methyl methanesulphonate, studied by fractionation of nuclei in a zonal centrifuge.", "content": "To relate repair of lesions in DNA with carcinogenesis, it is necessary to study repair in the intact animal under conditions which will and will not induce cancer. The methods used to study the replications stage of repair in isolated cells are not suitable for use in the intact animal. A method is presented which depends on the fact that during cell replication the nuclei enlarge, and may be separated from nuclei of non-replicating cells by rate zonal centrifugation on a sucrose gradient in a zonal rotor. Thus incorporation of [3H]thymidine as a result of de novo synthesis of DNA in replicating nuclei can be separated from incorporation due to repair synthesis in non-replicating nuclei. Treatment of animals with dimethylnitrosamine or with methyl methanesulphonate produced a \"repair-type\" profile, which contrasted with that given by liver nuclei from untreated animals, or from animals in which DNA synthesis had been reduced by treatment with cycloheximide, a compound which is not known to cause direct damage to DNA. Evidence is presented which suggests that the method is a rapid sensitive test for the occurrence of repair replication of some kind in the liver of the intact animal.", "contents": "Repair replication of DNA in the intact animal following treatment with dimethylnitrosamine and with methyl methanesulphonate, studied by fractionation of nuclei in a zonal centrifuge. To relate repair of lesions in DNA with carcinogenesis, it is necessary to study repair in the intact animal under conditions which will and will not induce cancer. The methods used to study the replications stage of repair in isolated cells are not suitable for use in the intact animal. A method is presented which depends on the fact that during cell replication the nuclei enlarge, and may be separated from nuclei of non-replicating cells by rate zonal centrifugation on a sucrose gradient in a zonal rotor. Thus incorporation of [3H]thymidine as a result of de novo synthesis of DNA in replicating nuclei can be separated from incorporation due to repair synthesis in non-replicating nuclei. Treatment of animals with dimethylnitrosamine or with methyl methanesulphonate produced a \"repair-type\" profile, which contrasted with that given by liver nuclei from untreated animals, or from animals in which DNA synthesis had been reduced by treatment with cycloheximide, a compound which is not known to cause direct damage to DNA. Evidence is presented which suggests that the method is a rapid sensitive test for the occurrence of repair replication of some kind in the liver of the intact animal."}
{"id": "PMID:183834", "title": "An enzymic analysis of a nuclear envelope fraction.", "content": "A rat liver nuclear envelope fraction isolated essentially by the technique of Monneron et al. (J. Cell Biol. 55, 104-125 (1972) is characterized by high levels of glucose-6-phosphatase and 5'-nucleotidase. A broadly specific nucleoside triphosphatase activity is present. Cytochromes b5 and P-450 as well as NADPH- and NADH-cytochrome c reductase activities are present but at lower levels than found in microsomes. Cytochrome c oxidase activity is low. RNA polymerase activity is absent from the nuclear envelope fraction. Cytochemistry shows that glucose-6-phosphatase activity is strong and restricted to the nuclear envelope of nuclei. 5'-Nucleotidase shows weak reaction deposit in whole nuclei but in contrast gives clear reaction deposit in isolated nuclear envelopes. Cytochemical reaction deposit due to nucleoside triphosphatase activity is not restricted to the nuclear envelope but is found to a larger extent within the nucleus.", "contents": "An enzymic analysis of a nuclear envelope fraction. A rat liver nuclear envelope fraction isolated essentially by the technique of Monneron et al. (J. Cell Biol. 55, 104-125 (1972) is characterized by high levels of glucose-6-phosphatase and 5'-nucleotidase. A broadly specific nucleoside triphosphatase activity is present. Cytochromes b5 and P-450 as well as NADPH- and NADH-cytochrome c reductase activities are present but at lower levels than found in microsomes. Cytochrome c oxidase activity is low. RNA polymerase activity is absent from the nuclear envelope fraction. Cytochemistry shows that glucose-6-phosphatase activity is strong and restricted to the nuclear envelope of nuclei. 5'-Nucleotidase shows weak reaction deposit in whole nuclei but in contrast gives clear reaction deposit in isolated nuclear envelopes. Cytochemical reaction deposit due to nucleoside triphosphatase activity is not restricted to the nuclear envelope but is found to a larger extent within the nucleus."}
{"id": "PMID:183835", "title": "Milk fat globule membranes. Inhibition by sucrose of the alkaline phosphomonoesterase.", "content": "Sucrose, a widely used agent in the preparation of membranes, inhibited the alkaline phosphomonoesterase of the milk fat globule membrane in both its membrane-bound and detergent-solubilized forms. The inhibition was kinetically competitive and reversible by dialysis. However, its mechanism was more complex than simple competition with substrate because: (a) sucrose induced the appearance of prolonged time-lags in the progress curves of the enzyme; (b) the extent of inhibition and of the time-lags depended on the age of the membrane preparation, the period of pre-exposure of the membranes to sucrose, and the temperature of pre-exposure. On the other hand the acid phosphomonoesterase and the phosphodiesterase activities also present in the membrane preparations were unaffected by the disaccharide.", "contents": "Milk fat globule membranes. Inhibition by sucrose of the alkaline phosphomonoesterase. Sucrose, a widely used agent in the preparation of membranes, inhibited the alkaline phosphomonoesterase of the milk fat globule membrane in both its membrane-bound and detergent-solubilized forms. The inhibition was kinetically competitive and reversible by dialysis. However, its mechanism was more complex than simple competition with substrate because: (a) sucrose induced the appearance of prolonged time-lags in the progress curves of the enzyme; (b) the extent of inhibition and of the time-lags depended on the age of the membrane preparation, the period of pre-exposure of the membranes to sucrose, and the temperature of pre-exposure. On the other hand the acid phosphomonoesterase and the phosphodiesterase activities also present in the membrane preparations were unaffected by the disaccharide."}
{"id": "PMID:183839", "title": "REM latency: a psychobiologic marker for primary depressive disease.", "content": "Previous investigations have indicated that one of the most consistent EEG sleep findings in depressive patients has been a shortened REM latency. On the basis of these studies, we have concluded that with the exception of drug withdrawal states (such as CNS depressant or amphetamine withdrawal and narcolepsy) shortened REM latency points to a strong affective component in the patient's illness. Short REM latency has also been observed in patients suffering from schizo-affective illness as well as in certain schizophrenic patients who require tricyclic antidepressants in their management. Furthermore, this psychobiologic marker is a persistent, rather than a transient phenomenon, and can be observed over a period of several weeks unless a patient's condition becomes more favorable through clinical intervention. This present report indicates that short REM latency is found in virtually all primary depressive illness and is absent in secondary depression. Thus, REM latency appears to be a dependable, measurable marker for diagnosing primary depression, and we argue that the phenomenon is independent of age, drug effect and changes in other sleep parameters. It is expected that EEG sleep and motor measurements can yield further significant data and improve differential diagnosis in psychiatry, in much the same way that laboratory data support other medical specialities.", "contents": "REM latency: a psychobiologic marker for primary depressive disease. Previous investigations have indicated that one of the most consistent EEG sleep findings in depressive patients has been a shortened REM latency. On the basis of these studies, we have concluded that with the exception of drug withdrawal states (such as CNS depressant or amphetamine withdrawal and narcolepsy) shortened REM latency points to a strong affective component in the patient's illness. Short REM latency has also been observed in patients suffering from schizo-affective illness as well as in certain schizophrenic patients who require tricyclic antidepressants in their management. Furthermore, this psychobiologic marker is a persistent, rather than a transient phenomenon, and can be observed over a period of several weeks unless a patient's condition becomes more favorable through clinical intervention. This present report indicates that short REM latency is found in virtually all primary depressive illness and is absent in secondary depression. Thus, REM latency appears to be a dependable, measurable marker for diagnosing primary depression, and we argue that the phenomenon is independent of age, drug effect and changes in other sleep parameters. It is expected that EEG sleep and motor measurements can yield further significant data and improve differential diagnosis in psychiatry, in much the same way that laboratory data support other medical specialities."}
{"id": "PMID:183836", "title": "[Study of conformational transitions in myosin using 2 types of spin label].", "content": "It is shown that three types of ESR spectra of myosin labeled with both acetate and acetamide spin labels are distinguished. These three types are the spectrum of initial preparation, myosin--ADP complex spectrum and the spectrum recorded during ATP hydrolysis. The ESR spectra of myosin labeled with acetate spin label are more sensitive to conformational changes of myosin induced by complex formation and temperature.", "contents": "[Study of conformational transitions in myosin using 2 types of spin label]. It is shown that three types of ESR spectra of myosin labeled with both acetate and acetamide spin labels are distinguished. These three types are the spectrum of initial preparation, myosin--ADP complex spectrum and the spectrum recorded during ATP hydrolysis. The ESR spectra of myosin labeled with acetate spin label are more sensitive to conformational changes of myosin induced by complex formation and temperature."}
{"id": "PMID:183844", "title": "XC-cell fusion induced by murine plasmocytoma cell. III. RNA gene expression correlated to syncytium formation.", "content": "The MF2 strain, a mouse myeloma derived cell line, was found to continuously produce C-type viral particles when maintained in tissue-culture. These cells when cultured in an ascitic form by injection to Balb/c mice lost this property. The ability to induce syncytia by cocultivation of the MF2 cell with XC-cells was shown to be related to the viral production. A DNA complementary to viral 70 S RNA was synthesized using the viral reverse-transcriptase endogenous activity. The quality of the probe is discussed and the expression of the viral genome among cellular poly A rich RNA varied concomitently to the syncytium inducing ability as evidenced by molecular hybridization experiments.", "contents": "XC-cell fusion induced by murine plasmocytoma cell. III. RNA gene expression correlated to syncytium formation. The MF2 strain, a mouse myeloma derived cell line, was found to continuously produce C-type viral particles when maintained in tissue-culture. These cells when cultured in an ascitic form by injection to Balb/c mice lost this property. The ability to induce syncytia by cocultivation of the MF2 cell with XC-cells was shown to be related to the viral production. A DNA complementary to viral 70 S RNA was synthesized using the viral reverse-transcriptase endogenous activity. The quality of the probe is discussed and the expression of the viral genome among cellular poly A rich RNA varied concomitently to the syncytium inducing ability as evidenced by molecular hybridization experiments."}
{"id": "PMID:183845", "title": "Electron-nuclear double resonance in melanins.", "content": "Electron-nuclear double resonance (ENDOR) signals from matrix protons interacting with the stable free radicals of \"A\"- and \"B\"-type melanins have been observed as a function of pH. In all samples the single line is similar in width and unusually narrow. The ENDOR reduction varies by more than a factor of 10, indicating a large sensitivity of relaxation properties of melanin to sample type. Signals were observed over a wide range of experimental conditions with good signal-to-noise ratio, establishing feasibility for further more detailed ENDOR studies. Incubation in D2O resulted in little change, indicating that the free radical is well buried or protected. No resolved hyperfine structure was seen, consistent with the generally accepted view that melanin is a heterogeneous polymer.", "contents": "Electron-nuclear double resonance in melanins. Electron-nuclear double resonance (ENDOR) signals from matrix protons interacting with the stable free radicals of \"A\"- and \"B\"-type melanins have been observed as a function of pH. In all samples the single line is similar in width and unusually narrow. The ENDOR reduction varies by more than a factor of 10, indicating a large sensitivity of relaxation properties of melanin to sample type. Signals were observed over a wide range of experimental conditions with good signal-to-noise ratio, establishing feasibility for further more detailed ENDOR studies. Incubation in D2O resulted in little change, indicating that the free radical is well buried or protected. No resolved hyperfine structure was seen, consistent with the generally accepted view that melanin is a heterogeneous polymer."}
{"id": "PMID:183846", "title": "Simultation of gradient and band propagation in the centrifuge.", "content": "A technique is developed for simulating the behavior of both the gradient-forming solute and macromolecular bands in a centrifuge. The change with time of the density gradient due to diffusion and sedimentation of the gradient-forming solute is calculated by a finite difference method, making use of the results of earlier work on the theory of the equilibrium density gradient. Using a perturbation technique, the concentration profiles of dilute bands of macromolecules are then calculated as they sediment and diffuse through the varying supporting gradient. Results of the stimulaion techniques are compared with experiment.", "contents": "Simultation of gradient and band propagation in the centrifuge. A technique is developed for simulating the behavior of both the gradient-forming solute and macromolecular bands in a centrifuge. The change with time of the density gradient due to diffusion and sedimentation of the gradient-forming solute is calculated by a finite difference method, making use of the results of earlier work on the theory of the equilibrium density gradient. Using a perturbation technique, the concentration profiles of dilute bands of macromolecules are then calculated as they sediment and diffuse through the varying supporting gradient. Results of the stimulaion techniques are compared with experiment."}
{"id": "PMID:183847", "title": "Structure of a DNA intercalation complex as determined by NMR using a paramagnetic probe.", "content": "Longitudinal relaxation rates of the protons of the 3,8-dimethyl-N-methyl-phenanthrolinium (DMP) cation in solutions containing DNA are strongly affected by the addition of the paramagnetic manganese (II) ions due to the electron-nuclear dipolar interaction in the ternary Mn-DNA-DMP Complex. Two possible models for the DMP-DNA intercalation complex are examined and one of them is unequivocally discriminated on the basis of the proton relaxation data. It is concluded that in the intercalation complex the long axis of the DMP molecule is almost perpendicular to the hydrogen bonds of the DNA base-pairs.", "contents": "Structure of a DNA intercalation complex as determined by NMR using a paramagnetic probe. Longitudinal relaxation rates of the protons of the 3,8-dimethyl-N-methyl-phenanthrolinium (DMP) cation in solutions containing DNA are strongly affected by the addition of the paramagnetic manganese (II) ions due to the electron-nuclear dipolar interaction in the ternary Mn-DNA-DMP Complex. Two possible models for the DMP-DNA intercalation complex are examined and one of them is unequivocally discriminated on the basis of the proton relaxation data. It is concluded that in the intercalation complex the long axis of the DMP molecule is almost perpendicular to the hydrogen bonds of the DNA base-pairs."}
{"id": "PMID:183848", "title": "Is the contractile response to exogenous acetylcholine due to a presynaptic effect?", "content": "Whether the contractile response induced by exogenous acetylcholine (ACh) chiefly involved the pre- or post-synaptic junctional site of the motor endplate was studied by using the cat gastrocnemius nerve muscle preparation poisoned with beta-bungarotoxin (beta-BuTX), a toxin isolated from the venom of Bungarus multicinctus which acts presynaptically. 2 After neuromuscular transmission was completely blocked by beta-BuTX, the dose-response curve of the contractile response induced by close intra-arterial injection of ACh, was compared with that of the control. No appreciable difference was observed. 3 In contrast, the response to ACh was completely abolished when neuromuscular transmission was blocked by alpha-bungarotoxin, a toxin isolated from the same venom which acts postsynaptically. 4 It is concluded that postjunctional site of the motor end-plate is chiefly involved in the contractile response produced by exogenous ACh.", "contents": "Is the contractile response to exogenous acetylcholine due to a presynaptic effect? Whether the contractile response induced by exogenous acetylcholine (ACh) chiefly involved the pre- or post-synaptic junctional site of the motor endplate was studied by using the cat gastrocnemius nerve muscle preparation poisoned with beta-bungarotoxin (beta-BuTX), a toxin isolated from the venom of Bungarus multicinctus which acts presynaptically. 2 After neuromuscular transmission was completely blocked by beta-BuTX, the dose-response curve of the contractile response induced by close intra-arterial injection of ACh, was compared with that of the control. No appreciable difference was observed. 3 In contrast, the response to ACh was completely abolished when neuromuscular transmission was blocked by alpha-bungarotoxin, a toxin isolated from the same venom which acts postsynaptically. 4 It is concluded that postjunctional site of the motor end-plate is chiefly involved in the contractile response produced by exogenous ACh."}
{"id": "PMID:183849", "title": "Prevention by zinc of cadmium-induced alterations in pancreatic and hepatic functions.", "content": "Subacute cadmium treatment (CdCl2, 1 mg/kg twice daily for 7 days) in rats disturbs glucose homeostasis as shown by hyperglycemia and decreased glucose tolerance associated with suppression of insulin release, enhancement of hepatic gluconeogenic enzymes and decrease in hepatic glycogen content. 2 Exposure to cadmium increases hepatic cyclic adenosine 3',5'-monophosphate (cyclic AMP) and this is accompanied by stimulation of basal, adrenaline- as well as glucagon-stimulated form(s) of adenylate cyclase. 3 In contrast to cadmium, subacute administration of zinc (ZnCl2, 2 mg/kg twice daily for 7 days) fails to alter the activities of hepatic gluconeogenic enzymes, cyclic AMP synthesis, as well as glucose clearance and insulin release in response to a glucose load. 4 Zinc, when administered at the same time as cadmium, prevents the cadmium-induced lesions in both hepatic and pancreatic functions. 5 The results are discussed in relation to the possible mechanisms of cadmium toxicity and to the role of sulphydryl groups in the protection exercised by zinc.", "contents": "Prevention by zinc of cadmium-induced alterations in pancreatic and hepatic functions. Subacute cadmium treatment (CdCl2, 1 mg/kg twice daily for 7 days) in rats disturbs glucose homeostasis as shown by hyperglycemia and decreased glucose tolerance associated with suppression of insulin release, enhancement of hepatic gluconeogenic enzymes and decrease in hepatic glycogen content. 2 Exposure to cadmium increases hepatic cyclic adenosine 3',5'-monophosphate (cyclic AMP) and this is accompanied by stimulation of basal, adrenaline- as well as glucagon-stimulated form(s) of adenylate cyclase. 3 In contrast to cadmium, subacute administration of zinc (ZnCl2, 2 mg/kg twice daily for 7 days) fails to alter the activities of hepatic gluconeogenic enzymes, cyclic AMP synthesis, as well as glucose clearance and insulin release in response to a glucose load. 4 Zinc, when administered at the same time as cadmium, prevents the cadmium-induced lesions in both hepatic and pancreatic functions. 5 The results are discussed in relation to the possible mechanisms of cadmium toxicity and to the role of sulphydryl groups in the protection exercised by zinc."}
{"id": "PMID:183850", "title": "An evaluation of psychiatric after-care in a developing country (Fiji).", "content": "The effectiveness of a community mental health programme in a developing country (Fiji) is examined. The programme was remarkable in that very little expertise was available in the community for it to be carried through. The results indicate that one category of hospital in-patient will subsequently derive significant benefit, namely the patient diagnosed as having schizophrenia who has been in a mental hospital more than once. Evidence from this study confirmed observations made by others that benign acute psychotic episodes are not infrequent in this sort of setting.", "contents": "An evaluation of psychiatric after-care in a developing country (Fiji). The effectiveness of a community mental health programme in a developing country (Fiji) is examined. The programme was remarkable in that very little expertise was available in the community for it to be carried through. The results indicate that one category of hospital in-patient will subsequently derive significant benefit, namely the patient diagnosed as having schizophrenia who has been in a mental hospital more than once. Evidence from this study confirmed observations made by others that benign acute psychotic episodes are not infrequent in this sort of setting."}
{"id": "PMID:183851", "title": "Urinary adenosine 3',5'-cyclic monophosphate: effects of electroconvulsive therapy.", "content": "Serial studies of urinary cyclic AMP in in-patients undergoing electroconvulsive therapy (ECT) have been carried out. No consistent pattern of change following ECT could be demonstrated. The results do not support earlier reports of large rises in urinary cAMP directly after administration of ECT.", "contents": "Urinary adenosine 3',5'-cyclic monophosphate: effects of electroconvulsive therapy. Serial studies of urinary cyclic AMP in in-patients undergoing electroconvulsive therapy (ECT) have been carried out. No consistent pattern of change following ECT could be demonstrated. The results do not support earlier reports of large rises in urinary cAMP directly after administration of ECT."}
{"id": "PMID:183852", "title": "The application of a digital whole body scanner to the dosimetry of intralymphatic 32P/131I Lipiodol.", "content": "A quantitative, digital-output, whole-body scanner in a low background area has been used in the dosimetry of 32P/131I Lipiodol for intralymphatic radiotherapy. Five patients with malignant melanoma received intralymphatic administrations of Lipiodol labelled with 6 mCi 32P and 1.5 mCi 131I. The 131I is used primarily as a tracer for external measurements and the 32P as the chief therapeutic agent. Whole body scans were made at intervals for up to 15 days using the digital scanner, with the spectrometer set over the 364 keV photopeak of 131I. On the same occasions complete gamma-spectra were obtained for these patients using a 2 m arc, single detector whole body counter. The method used in estimating the activity at various sites in the body from the digital whole body scans is described and problems that arise in using 131I as a tracer for 32P Lipiodol in this work are discussed. For the administered activities mentioned above, maximum absorbed doses to the lymph nodes were found to range from 30-96 krad with a mean value of 51 krad. Uptake of radioactivity was also found in the lungs, resulting in absorbed doses of 350-960 rad with a mean value of 540 rad.", "contents": "The application of a digital whole body scanner to the dosimetry of intralymphatic 32P/131I Lipiodol. A quantitative, digital-output, whole-body scanner in a low background area has been used in the dosimetry of 32P/131I Lipiodol for intralymphatic radiotherapy. Five patients with malignant melanoma received intralymphatic administrations of Lipiodol labelled with 6 mCi 32P and 1.5 mCi 131I. The 131I is used primarily as a tracer for external measurements and the 32P as the chief therapeutic agent. Whole body scans were made at intervals for up to 15 days using the digital scanner, with the spectrometer set over the 364 keV photopeak of 131I. On the same occasions complete gamma-spectra were obtained for these patients using a 2 m arc, single detector whole body counter. The method used in estimating the activity at various sites in the body from the digital whole body scans is described and problems that arise in using 131I as a tracer for 32P Lipiodol in this work are discussed. For the administered activities mentioned above, maximum absorbed doses to the lymph nodes were found to range from 30-96 krad with a mean value of 51 krad. Uptake of radioactivity was also found in the lungs, resulting in absorbed doses of 350-960 rad with a mean value of 540 rad."}
{"id": "PMID:183858", "title": "Peripheral nerve fibre changes in asymptomatic children of patients with familial amyloid polyneuropathy.", "content": "Sural nerve biopsies of 5 children of patients with familial amyloid polyneuropathy were studied by electronmicroscopy. The subjects were 14-17 years old and were in normal health. Neurological examination was negative. In none of the sural nerve specimens were there any amyloid deposits. In Case 4 no fine structural changes were detected. In the remaining 4 cases, there were frequent deposits of glycogen and clusters of multimembranous bodies in the Schwann-cell crescents of large myelinated fibres which presented infoldings of the myelin sheath, irregular myelin lamellation and a great number of Schmidt-Lanterman incisures. In one nerve fasciculus of Case 5 the myelin sheaths of some large myelinated fibres were extremely thickened; the axoplasm exhibited dilated vesicles and disordered microfilaments. These findings were taken as evidence of the occurrence of nerve fibre lesions at the pre-symptomatic stage of the disease, which seem to precede the appearance of amyloid deposition. The lesions affected primarily the Schwann cell and myelin sheath, and spared the unmyelinated fibres.", "contents": "Peripheral nerve fibre changes in asymptomatic children of patients with familial amyloid polyneuropathy. Sural nerve biopsies of 5 children of patients with familial amyloid polyneuropathy were studied by electronmicroscopy. The subjects were 14-17 years old and were in normal health. Neurological examination was negative. In none of the sural nerve specimens were there any amyloid deposits. In Case 4 no fine structural changes were detected. In the remaining 4 cases, there were frequent deposits of glycogen and clusters of multimembranous bodies in the Schwann-cell crescents of large myelinated fibres which presented infoldings of the myelin sheath, irregular myelin lamellation and a great number of Schmidt-Lanterman incisures. In one nerve fasciculus of Case 5 the myelin sheaths of some large myelinated fibres were extremely thickened; the axoplasm exhibited dilated vesicles and disordered microfilaments. These findings were taken as evidence of the occurrence of nerve fibre lesions at the pre-symptomatic stage of the disease, which seem to precede the appearance of amyloid deposition. The lesions affected primarily the Schwann cell and myelin sheath, and spared the unmyelinated fibres."}
{"id": "PMID:183860", "title": "Calcium dependency of excitatory chemical synaptic transmission in the frog cerebellum in vitro.", "content": "Chemical synaptic transmission was studied with microelectrode techniques in isolated frog cerebella maintained in vitro. Purkinje cell (PC) EPSPs, elicited by selective monosynaptic electrical stimulation of both the parallel fiber (PF) and climbing fiber (CF) inputs, could be inverted by depolarizing (outward) current injections. Evoked synaptic transmission at both junctions was reduced by lowering the extracellular concentration of calcium ions ([Ca2+]) below 2 mM. Raising [Ca2+] above 2 mM to 8 mM did not further increase synaptic transmission. Mg2+, Sr2+, and Ba2+ did not substitute for Ca2+ in the transmission process.", "contents": "Calcium dependency of excitatory chemical synaptic transmission in the frog cerebellum in vitro. Chemical synaptic transmission was studied with microelectrode techniques in isolated frog cerebella maintained in vitro. Purkinje cell (PC) EPSPs, elicited by selective monosynaptic electrical stimulation of both the parallel fiber (PF) and climbing fiber (CF) inputs, could be inverted by depolarizing (outward) current injections. Evoked synaptic transmission at both junctions was reduced by lowering the extracellular concentration of calcium ions ([Ca2+]) below 2 mM. Raising [Ca2+] above 2 mM to 8 mM did not further increase synaptic transmission. Mg2+, Sr2+, and Ba2+ did not substitute for Ca2+ in the transmission process."}
{"id": "PMID:183861", "title": "Selective antagonism of frog cerebellar synaptic transmission by manganese and cobalt ions.", "content": "Parallel fiber-Purkinje cell synaptic transmission of the frog cerebellum can be selectively blocked by Mn2+ and Co2+. The interaction of these cations with Ca2+ indicates that they act, as has been found for other chemical synapses, at the presynaptic terminals where Ca2+ is required for release of neurotransmitters. Climbing fiber-Purkinje cell synaptic transmission was similarly blocked by Mg2+, Mn2+ and Co2+.", "contents": "Selective antagonism of frog cerebellar synaptic transmission by manganese and cobalt ions. Parallel fiber-Purkinje cell synaptic transmission of the frog cerebellum can be selectively blocked by Mn2+ and Co2+. The interaction of these cations with Ca2+ indicates that they act, as has been found for other chemical synapses, at the presynaptic terminals where Ca2+ is required for release of neurotransmitters. Climbing fiber-Purkinje cell synaptic transmission was similarly blocked by Mg2+, Mn2+ and Co2+."}
{"id": "PMID:183862", "title": "Electrophysiology of Purkinje neurons in the weaver mouse: iontophoresis of neurotransmitters and cyclic nucleotides, and stimulation of the nucleus locus coeruleus.", "content": "We compared the Purkinje cells of adult normal and weaver mutant (wv/wv) mice by iontophoretic and electrophysiological tests. Although weaver Purkinje cells fire spontaneously at a rate (38 Hz) similar to normal mouse neurons (40 Hz), several abnormalities of firing were seen: high frequency bursts of single (simple) spikes occurred in 5-10-sec episodes in 38% of weaver cells, compared to 8% in normal mice; spontaneous complex spikes (climbing fiber-like burst responses) occurred in several different forms in a given Purkinje cell. As in normal mice and rats, the spontaneous single spike activity is readily depressed by electrical stimulation of the locus coeruleus, the presumed source of a dense noradrenergic plexus in the weaver cerebellar cortex. In a preliminary experiment the adrenergic blocking agent, fluphenazine, antagonized the responses to locus coeruleus stimulation. Iontophoresis of norepinephrine (NE), GABA and serotonin (5-HT) also uniformly depressed Purkinje cell single spike activity in all normal and weaver mice; cyclic AMP depressed 55% of normal and 70% of weaver Purkinje cells. Glutamate was always excitatory. The only qualitative difference was seen with acetylcholine, which was mostly inhibitory in normal mouse, but increased the firing rate in 42% of weaver Purkinje neurons. Cyclic GMP was predominantly excitatory in both types. Thus, despite the absence of parallel fibers, weaver Purkinje neurons grossly resemble normal Purkinje cells electrophysiologically as well as morphologically. Since several sites of indirect presynaptic actions are eliminated in weaver, our results further substantiate the direct post-synaptic inhibitory nature of GABA, 5-HT and NE, and the noradrenergic pathway from locus coeruleus to Purkinje cells. Similarly, consistent inhibitory responses to cyclic AMP in the weaver support the previously hypothesized role of cyclic AMP in the post-synaptic inhibitory response to NE.", "contents": "Electrophysiology of Purkinje neurons in the weaver mouse: iontophoresis of neurotransmitters and cyclic nucleotides, and stimulation of the nucleus locus coeruleus. We compared the Purkinje cells of adult normal and weaver mutant (wv/wv) mice by iontophoretic and electrophysiological tests. Although weaver Purkinje cells fire spontaneously at a rate (38 Hz) similar to normal mouse neurons (40 Hz), several abnormalities of firing were seen: high frequency bursts of single (simple) spikes occurred in 5-10-sec episodes in 38% of weaver cells, compared to 8% in normal mice; spontaneous complex spikes (climbing fiber-like burst responses) occurred in several different forms in a given Purkinje cell. As in normal mice and rats, the spontaneous single spike activity is readily depressed by electrical stimulation of the locus coeruleus, the presumed source of a dense noradrenergic plexus in the weaver cerebellar cortex. In a preliminary experiment the adrenergic blocking agent, fluphenazine, antagonized the responses to locus coeruleus stimulation. Iontophoresis of norepinephrine (NE), GABA and serotonin (5-HT) also uniformly depressed Purkinje cell single spike activity in all normal and weaver mice; cyclic AMP depressed 55% of normal and 70% of weaver Purkinje cells. Glutamate was always excitatory. The only qualitative difference was seen with acetylcholine, which was mostly inhibitory in normal mouse, but increased the firing rate in 42% of weaver Purkinje neurons. Cyclic GMP was predominantly excitatory in both types. Thus, despite the absence of parallel fibers, weaver Purkinje neurons grossly resemble normal Purkinje cells electrophysiologically as well as morphologically. Since several sites of indirect presynaptic actions are eliminated in weaver, our results further substantiate the direct post-synaptic inhibitory nature of GABA, 5-HT and NE, and the noradrenergic pathway from locus coeruleus to Purkinje cells. Similarly, consistent inhibitory responses to cyclic AMP in the weaver support the previously hypothesized role of cyclic AMP in the post-synaptic inhibitory response to NE."}
{"id": "PMID:183863", "title": "Enzymic preparation of neurosecretosome- and pituicyte-enriched fractions from the rat neurohypophysis.", "content": "A microcellular dispersion procedure for the rat neurohypophysis was developed, comprising tissue softening and dissociation using a special sieving sytringe. In preparatory studies the influence of mesh width, and treatment with trypsin, pronase or collagenase-hyaluronidase was investigated using light and electron microscopy, as well as with microchemistry by means of protein and lactate dehydrogenase activity determinations. Trypsinization gave the best results. In the final adopted procedure, 3 incubated neurohypophyses were sequentially sieved through a 200- and a 50-mum mesh. The resulting 50-mul dispersion was found to contain numerous ultrastructurally well-preserved pinched-off axonal endings (neurosecretosomes), and pituicytes often revealing processes. On the basis of DNA and oxytocin assays 11% of the pituicytes and 28% of the axonal cytoplasm were recovered. Oxytocin immunofluorescence microscopy showed hormone within the neurosecretosomes, but often also in the cytoplasm of pituicytes. Microdensity gradient centrifugation was performed on neurohypophyseal disperions, in order to obtain fractions enriched for neurosecretosomes and pituicytes. Fractions were characterized by means of phase contrast, oxytocin immunofluorescence and electron microscopy, as well as by oxytocin and DNA assays as respective markers. With a 10:14:22% (w/v) Ficoll gradient, fractions were obtained for which the relative purification was by a factor of 4 on the basis of DNA/oxytocin ratios.", "contents": "Enzymic preparation of neurosecretosome- and pituicyte-enriched fractions from the rat neurohypophysis. A microcellular dispersion procedure for the rat neurohypophysis was developed, comprising tissue softening and dissociation using a special sieving sytringe. In preparatory studies the influence of mesh width, and treatment with trypsin, pronase or collagenase-hyaluronidase was investigated using light and electron microscopy, as well as with microchemistry by means of protein and lactate dehydrogenase activity determinations. Trypsinization gave the best results. In the final adopted procedure, 3 incubated neurohypophyses were sequentially sieved through a 200- and a 50-mum mesh. The resulting 50-mul dispersion was found to contain numerous ultrastructurally well-preserved pinched-off axonal endings (neurosecretosomes), and pituicytes often revealing processes. On the basis of DNA and oxytocin assays 11% of the pituicytes and 28% of the axonal cytoplasm were recovered. Oxytocin immunofluorescence microscopy showed hormone within the neurosecretosomes, but often also in the cytoplasm of pituicytes. Microdensity gradient centrifugation was performed on neurohypophyseal disperions, in order to obtain fractions enriched for neurosecretosomes and pituicytes. Fractions were characterized by means of phase contrast, oxytocin immunofluorescence and electron microscopy, as well as by oxytocin and DNA assays as respective markers. With a 10:14:22% (w/v) Ficoll gradient, fractions were obtained for which the relative purification was by a factor of 4 on the basis of DNA/oxytocin ratios."}
{"id": "PMID:183865", "title": "Effects of ergosterol on bone mineralisation in chicks given cholecalciferol or ergocalciferol.", "content": "Groups of chicks were given diets containing cholecalciferol or ergocalciferol supplemented with 0, 0-1, 1 or 10 g ergosterol/kg. 2. Ergosterol had no significant effect on growth, on the plasma concentration of calcium or on the content of bone-ash, indicating that it did not impair the absorption of either form of vitamin D. 3. An explanation is given for the apparent disagreement in the published findings on the relative anti-rachitic potencies of ergocalciferol and cholecalciferol in the chick.", "contents": "Effects of ergosterol on bone mineralisation in chicks given cholecalciferol or ergocalciferol. Groups of chicks were given diets containing cholecalciferol or ergocalciferol supplemented with 0, 0-1, 1 or 10 g ergosterol/kg. 2. Ergosterol had no significant effect on growth, on the plasma concentration of calcium or on the content of bone-ash, indicating that it did not impair the absorption of either form of vitamin D. 3. An explanation is given for the apparent disagreement in the published findings on the relative anti-rachitic potencies of ergocalciferol and cholecalciferol in the chick."}
{"id": "PMID:183869", "title": "[Correlation between permeabiltiy to albumin and levels of cyclic adenosine monophosphate in the incubated rat mesentery].", "content": "Histamine, bradykinin and prostaglandin E1 increase the permeability coefficient of albumin; this effect is mimicked by dibutyryl-cAMP and by theophylline. They also cause a significant rise in the cAMP levels of the incubated tissue. Serotonin has lesser activities on these parameters. Presumably, the first three mediators control the transcellular passage of albumin by increasing the cAMP content of the tissue, serotonin being less effective. These findings on the mesentery seem to have a couterpart in vascular tissue as shown by others using different methods.", "contents": "[Correlation between permeabiltiy to albumin and levels of cyclic adenosine monophosphate in the incubated rat mesentery]. Histamine, bradykinin and prostaglandin E1 increase the permeability coefficient of albumin; this effect is mimicked by dibutyryl-cAMP and by theophylline. They also cause a significant rise in the cAMP levels of the incubated tissue. Serotonin has lesser activities on these parameters. Presumably, the first three mediators control the transcellular passage of albumin by increasing the cAMP content of the tissue, serotonin being less effective. These findings on the mesentery seem to have a couterpart in vascular tissue as shown by others using different methods."}
{"id": "PMID:183870", "title": "[Action of lithium salts on hepatocytes in histiotypic culture].", "content": "Addition of lithium salts to cultures of hepatocytes increases glycogen in these cells. Glycogenolytic action of glucagone or AMPc becomes slow. Toxic action of paraquat is suppressed.", "contents": "[Action of lithium salts on hepatocytes in histiotypic culture]. Addition of lithium salts to cultures of hepatocytes increases glycogen in these cells. Glycogenolytic action of glucagone or AMPc becomes slow. Toxic action of paraquat is suppressed."}
{"id": "PMID:183871", "title": "[Demonstration of specific receptor sites of 3, 5, 3'-triiodo-L-thyronine on isolated rat hepatocytes].", "content": "The polarographic respiration studies of isolated liver cells from normal and thyroidectomised rats show that oxygen consumption rate is decreased by 40% after thyroidectomy. The number of specific binding sites estimated with 125I labelled T3 experiments, is about 130 per cell.", "contents": "[Demonstration of specific receptor sites of 3, 5, 3'-triiodo-L-thyronine on isolated rat hepatocytes]. The polarographic respiration studies of isolated liver cells from normal and thyroidectomised rats show that oxygen consumption rate is decreased by 40% after thyroidectomy. The number of specific binding sites estimated with 125I labelled T3 experiments, is about 130 per cell."}
{"id": "PMID:183872", "title": "[Mast-cell rosettes in the immunized rat].", "content": "After stimulation by ovalbumin + Bordetella pertussis, rat peritoneal mast cells can form rosettes with antigen-coated erythrocytes. This phenomenon is inhibited by previous incubation of mast cells with antigen; it is attributed to apparition of membrane-bound anaphylactic antibody. The variations of percentage of rosette forming mast cells during the course of immunization are reported and compared with P.C.A. titers.", "contents": "[Mast-cell rosettes in the immunized rat]. After stimulation by ovalbumin + Bordetella pertussis, rat peritoneal mast cells can form rosettes with antigen-coated erythrocytes. This phenomenon is inhibited by previous incubation of mast cells with antigen; it is attributed to apparition of membrane-bound anaphylactic antibody. The variations of percentage of rosette forming mast cells during the course of immunization are reported and compared with P.C.A. titers."}
{"id": "PMID:183873", "title": "[Induction of cytochrome P-450 and b5 of the mouse liver by phenytoin during chronic hypoxia (Fi02 : 0,08)].", "content": "During chronic hypoxia at sea level (FiO2 : 0,08) the liver concentrations of cytochrome P 450 and b5 decreased. Phenytoin administration induces an increase in cytochrome P 450 and b5 liver content. The hydroxylation of phenytoin that was decreased at low level of cytochrome P 450 and oxygen, reached again a normal level after induction of cytochrome P 450 in spite of the persistency of a low level of available oxygen. Liver cytochrome P 450 concentration is the main limiting factor of phenytoin hydroxylation.", "contents": "[Induction of cytochrome P-450 and b5 of the mouse liver by phenytoin during chronic hypoxia (Fi02 : 0,08)]. During chronic hypoxia at sea level (FiO2 : 0,08) the liver concentrations of cytochrome P 450 and b5 decreased. Phenytoin administration induces an increase in cytochrome P 450 and b5 liver content. The hydroxylation of phenytoin that was decreased at low level of cytochrome P 450 and oxygen, reached again a normal level after induction of cytochrome P 450 in spite of the persistency of a low level of available oxygen. Liver cytochrome P 450 concentration is the main limiting factor of phenytoin hydroxylation."}
{"id": "PMID:183874", "title": "[Role of various regulation factors of interrenal gland activity in response to stress in the green frog Rana esculenta L].", "content": "The effects of an ether stress on the corticosterone levels were studied in variously experimented frogs. The removal of the distal lobe of the pituitary gland, with preservation of the intermediate lobe which contains also ACTH, suppresses, as total hypophysectomy, the increase of corticosterone level observed in normal frogs. The administration of dexamethasone reduces but not suppresses this increase. A second ether stress 20 minutes after the first is effective. The injection of frog plasma treated or not with an corticosteroid adsorbant do not alter the response to stress. These results suggest that modifications of corticosterone level, in some limits, do not disturb the effects of a stress.", "contents": "[Role of various regulation factors of interrenal gland activity in response to stress in the green frog Rana esculenta L]. The effects of an ether stress on the corticosterone levels were studied in variously experimented frogs. The removal of the distal lobe of the pituitary gland, with preservation of the intermediate lobe which contains also ACTH, suppresses, as total hypophysectomy, the increase of corticosterone level observed in normal frogs. The administration of dexamethasone reduces but not suppresses this increase. A second ether stress 20 minutes after the first is effective. The injection of frog plasma treated or not with an corticosteroid adsorbant do not alter the response to stress. These results suggest that modifications of corticosterone level, in some limits, do not disturb the effects of a stress."}
{"id": "PMID:183875", "title": "[Renal production and excretion of AMPc after intravenous infusion of salmon calcitonin in man].", "content": "Intravenous infusion of salmon calcitonin in man produced an increase in the plasma levels and urinary excretion of cyclic AMP. This study demonstrates a net extraction of cyclic AMP from plasma by the kidneys but salmon calcitonin does not act only on the kidney and stimulates the production of cyclic AMP in extra renal tissues. The excess of cyclic AMP formed is catabolized by the kidneys.", "contents": "[Renal production and excretion of AMPc after intravenous infusion of salmon calcitonin in man]. Intravenous infusion of salmon calcitonin in man produced an increase in the plasma levels and urinary excretion of cyclic AMP. This study demonstrates a net extraction of cyclic AMP from plasma by the kidneys but salmon calcitonin does not act only on the kidney and stimulates the production of cyclic AMP in extra renal tissues. The excess of cyclic AMP formed is catabolized by the kidneys."}
{"id": "PMID:183876", "title": "[Immunization of the nude mouse against mouse hepatitis virus through the transfer of sensitized lymphocytes].", "content": "Nude (nu/nu) mice failed to resist to virulent mouse hepatitis virus (MHV) infection after vaccination with inactivated virus. Resistance was induced in nu/nu mice by the transfer of spleen cells from heterozygous haired (nu/ +) mice concomitantly with the vaccination, and the effect was more remarkable with spleen cells from immunized nu/ + mice. Antibody was demonstrable in nu/nu mice having received nu/ + cells and survived challenge infection.", "contents": "[Immunization of the nude mouse against mouse hepatitis virus through the transfer of sensitized lymphocytes]. Nude (nu/nu) mice failed to resist to virulent mouse hepatitis virus (MHV) infection after vaccination with inactivated virus. Resistance was induced in nu/nu mice by the transfer of spleen cells from heterozygous haired (nu/ +) mice concomitantly with the vaccination, and the effect was more remarkable with spleen cells from immunized nu/ + mice. Antibody was demonstrable in nu/nu mice having received nu/ + cells and survived challenge infection."}
{"id": "PMID:183877", "title": "Neuromuscular block by neomycin in the cat.", "content": "The neuromuscular block produced by neomycin is unique. Despite nearly complete blockade of the twitch the tetanus is not blocked and does not fade. The pathognomonic post-tetanic exhaustion has not been reported previously. Anticholinesterases and calcium antagonize the block, but the antagonism may not be complete. Germine antagonizes the block in the cat, but its clinical value has not been tested. These characteristics of neuromuscular block by neomycin strongly suggest respiratory support and sedation to decrease the respiratory drive, rather than attempts at antagonism, as the rational management of patients suffering from toxic paralysis due to neomycin.", "contents": "Neuromuscular block by neomycin in the cat. The neuromuscular block produced by neomycin is unique. Despite nearly complete blockade of the twitch the tetanus is not blocked and does not fade. The pathognomonic post-tetanic exhaustion has not been reported previously. Anticholinesterases and calcium antagonize the block, but the antagonism may not be complete. Germine antagonizes the block in the cat, but its clinical value has not been tested. These characteristics of neuromuscular block by neomycin strongly suggest respiratory support and sedation to decrease the respiratory drive, rather than attempts at antagonism, as the rational management of patients suffering from toxic paralysis due to neomycin."}
{"id": "PMID:183878", "title": "Synthesis of diphosphoinositide by a supernatant fraction from Acanthamoeba castellanii.", "content": "Homogenates of the free-living amoeba Acanthamoeba castellanii incorporate phosphate from [gamma-32P]ATP into a lipid which co-chromatographs with diphosphoinositide on one- and two dimensional chromatography. Incorporation into lipids similar in mobility to triphosphoinositide is not detected. The product co-chromatographs with diphosphoinositide whether exogenous phosphatidylinositol or total amoeba lipid is the substrate. The inositide kinase is almost entirely located in the supernatant fraction after centrifugation at 100 000 g. Incorporation of phosphate from [gamma-32P]ATP is linear for at least 15 min in the presence of 0.5 mM phosphatidylinositol. The enzyme requires Mg2+ of Mn2+ as well as ATP and it is not affected by low concentrations of Ca2+. The apparent Km for phosphatidylinositol in 2 mM. Both ADP and cAMP inhibit the reaction.", "contents": "Synthesis of diphosphoinositide by a supernatant fraction from Acanthamoeba castellanii. Homogenates of the free-living amoeba Acanthamoeba castellanii incorporate phosphate from [gamma-32P]ATP into a lipid which co-chromatographs with diphosphoinositide on one- and two dimensional chromatography. Incorporation into lipids similar in mobility to triphosphoinositide is not detected. The product co-chromatographs with diphosphoinositide whether exogenous phosphatidylinositol or total amoeba lipid is the substrate. The inositide kinase is almost entirely located in the supernatant fraction after centrifugation at 100 000 g. Incorporation of phosphate from [gamma-32P]ATP is linear for at least 15 min in the presence of 0.5 mM phosphatidylinositol. The enzyme requires Mg2+ of Mn2+ as well as ATP and it is not affected by low concentrations of Ca2+. The apparent Km for phosphatidylinositol in 2 mM. Both ADP and cAMP inhibit the reaction."}
{"id": "PMID:183880", "title": "Effects of indomethacin and aminoglutethimide phosphate in vivo on luteinizing-hormone-induced alterations of cyclic adenosine monophosphate, prostaglandin F, and steroid levels in preovulatory rat ovaries.", "content": "Changes in levels of cyclic adenosine monophosphate (cAMP), prostaglandin F (PGF), progesterone, testosterone, and estradiol-17beta, in preovulatory rat ovaries induced by exogenous luteinizing hormone (LH) have been measured. Ovarian cAMP reached maximal levels 15 min and 1h after LH administration by intravenous and intraperitoneal routes, respectively, and then declined to pre-LH levels by 8 h. Progesterone levels in ovaries and serum rose approximately in parallel with cAMP, but remained elevated throughout the 8-h sampling period. Ovarian testosterone increased to maximal levels 1 h after LH injection, followed by a rapid decline to below pre-LH levels. Ovarian estradiol-17beat concentrations declined steadily throughout the sampling period, reaching almost undetectable levels 8 h after LH treatment. Elevated ovarian PGF levels were observed only at the 4- and 8-h sampling times. Indomethacin treatment, 1 h before LH, prevented the LH-induced increase in ovarian PGF levels, depressed PGF values considerably in saline-injected controls but produced no significant inhibition of ovarian cAMP and progesterone levels. Aminoglutethimide phosphate depressed ovarian concentrations of all three steroids (progesterone, testosterone, and estradiol-17beta) to essentially undetectable levels, both in control and LH-injected rats, but did not alter the LH-induced changes in ovarian cAMP and PGF levels. These observations support the concept of cAMP as a mediator of the LH-induced alterations of ovarian steroidogenesis in vivo during the preovulatory period, but argue against an obligatory role of PGF in this process.", "contents": "Effects of indomethacin and aminoglutethimide phosphate in vivo on luteinizing-hormone-induced alterations of cyclic adenosine monophosphate, prostaglandin F, and steroid levels in preovulatory rat ovaries. Changes in levels of cyclic adenosine monophosphate (cAMP), prostaglandin F (PGF), progesterone, testosterone, and estradiol-17beta, in preovulatory rat ovaries induced by exogenous luteinizing hormone (LH) have been measured. Ovarian cAMP reached maximal levels 15 min and 1h after LH administration by intravenous and intraperitoneal routes, respectively, and then declined to pre-LH levels by 8 h. Progesterone levels in ovaries and serum rose approximately in parallel with cAMP, but remained elevated throughout the 8-h sampling period. Ovarian testosterone increased to maximal levels 1 h after LH injection, followed by a rapid decline to below pre-LH levels. Ovarian estradiol-17beat concentrations declined steadily throughout the sampling period, reaching almost undetectable levels 8 h after LH treatment. Elevated ovarian PGF levels were observed only at the 4- and 8-h sampling times. Indomethacin treatment, 1 h before LH, prevented the LH-induced increase in ovarian PGF levels, depressed PGF values considerably in saline-injected controls but produced no significant inhibition of ovarian cAMP and progesterone levels. Aminoglutethimide phosphate depressed ovarian concentrations of all three steroids (progesterone, testosterone, and estradiol-17beta) to essentially undetectable levels, both in control and LH-injected rats, but did not alter the LH-induced changes in ovarian cAMP and PGF levels. These observations support the concept of cAMP as a mediator of the LH-induced alterations of ovarian steroidogenesis in vivo during the preovulatory period, but argue against an obligatory role of PGF in this process."}
{"id": "PMID:183881", "title": "Isolation and carbohydrate composition of glycopeptides of human apo low-density lipoprotein from normal and type II hyperlipoproteinemic subjects.", "content": "Glycopeptides were prepared from the delipidized protein of low-density lipoprotein (LDL, d=1.019-1.063) of three normal and three familial heterozygous type II hyperlipoproteinemic (HLP) subjects. The glycopeptides of all subjects were resolved into three groups by gel filtration on Bio-Gel P6 following papain (EC 3.4.22.2) digestion and initial purification on Bio-Gel P2. In normal individuals the component of largest molecular weight (F-1) contained mannose (Man), N-acetyl glucosamine (GlcNAc) galactose (Gal), and N-acetyl neuraminic acid (NANA) in the respective amounts of 45.9 +/- 6.7, 37.3 +/- 5.9, 28.6 +/- 3.4, and 27.0 +/- 3.9 nmol/mg original apoprotein. The group of smallest molecular weight (F-3) contained essentially only Man (25.8 +/- 1.5 nmol/mg protein) and GlcNac (3.0 +/- 0.4 nmol/mg protein) with traces of Gal and NANA. A group of intermediate molecular weight (F-2) exhibited considerable heterogeneity and contained Man, GlcNAc, Gal, and NANA in the amounts of 45.9 +/- 5.1, 18.3 +/- 1.7, 11.0 %/- 1.7, and 7.7 %/- 1.2 nmol/mg protein. While the major portion of NANA (78%), Gal (71%), and GlcNAc (64%) was present in F-1, approximately 22% of the total Man was in F-3. No major differences were detected in the carbohydrate composition of the three glycopeptide fractions of LDL apoptotein from normal and Type II subjects.", "contents": "Isolation and carbohydrate composition of glycopeptides of human apo low-density lipoprotein from normal and type II hyperlipoproteinemic subjects. Glycopeptides were prepared from the delipidized protein of low-density lipoprotein (LDL, d=1.019-1.063) of three normal and three familial heterozygous type II hyperlipoproteinemic (HLP) subjects. The glycopeptides of all subjects were resolved into three groups by gel filtration on Bio-Gel P6 following papain (EC 3.4.22.2) digestion and initial purification on Bio-Gel P2. In normal individuals the component of largest molecular weight (F-1) contained mannose (Man), N-acetyl glucosamine (GlcNAc) galactose (Gal), and N-acetyl neuraminic acid (NANA) in the respective amounts of 45.9 +/- 6.7, 37.3 +/- 5.9, 28.6 +/- 3.4, and 27.0 +/- 3.9 nmol/mg original apoprotein. The group of smallest molecular weight (F-3) contained essentially only Man (25.8 +/- 1.5 nmol/mg protein) and GlcNac (3.0 +/- 0.4 nmol/mg protein) with traces of Gal and NANA. A group of intermediate molecular weight (F-2) exhibited considerable heterogeneity and contained Man, GlcNAc, Gal, and NANA in the amounts of 45.9 +/- 5.1, 18.3 +/- 1.7, 11.0 %/- 1.7, and 7.7 %/- 1.2 nmol/mg protein. While the major portion of NANA (78%), Gal (71%), and GlcNAc (64%) was present in F-1, approximately 22% of the total Man was in F-3. No major differences were detected in the carbohydrate composition of the three glycopeptide fractions of LDL apoptotein from normal and Type II subjects."}
{"id": "PMID:183882", "title": "Regulation by zinc and adenosine 3',5'-cyclic monophosphate of growth and citric acid accumulation in Aspergillus niger.", "content": "The citric acid fermentation by Aspergillus niger is divided into two consecutive phases, growth phase when the cells proliferate but do not accumulate citrate, followed by an accumulating phase when they excrete citrate but do not proliferate. The phase alternative was controlled by the concentration of zinc: high zinc (2 muM) maintained growth phase, and a zinc 'deficiency' apparently signaled the ransition to the accumulating phase. Cyclic AMP affected the rates of growth and acidogenesis when added to cultures growing at low but not at high zinc: that is, cAMP did not induce the phase transition, zinc deficiency did, Cyclic AMP enhanced growth early in the fermentation, but at later stages the response of the mycelia to cAMP changed, and then cAMP inhibited growth. When citrate eventually began to accumulate cAMP augmented its sypthesis. The growth and acidogenic responses were quite specific to cAMP, and were sensitive to concentrations of about 1 muM. Cyclic AMP also either promoted or retarded the appearance of an unidentified yellow pigment. It is proposed that the growth and accumulating phases are distinct differentiated states, at least with respect to cAMP metabolism.", "contents": "Regulation by zinc and adenosine 3',5'-cyclic monophosphate of growth and citric acid accumulation in Aspergillus niger. The citric acid fermentation by Aspergillus niger is divided into two consecutive phases, growth phase when the cells proliferate but do not accumulate citrate, followed by an accumulating phase when they excrete citrate but do not proliferate. The phase alternative was controlled by the concentration of zinc: high zinc (2 muM) maintained growth phase, and a zinc 'deficiency' apparently signaled the ransition to the accumulating phase. Cyclic AMP affected the rates of growth and acidogenesis when added to cultures growing at low but not at high zinc: that is, cAMP did not induce the phase transition, zinc deficiency did, Cyclic AMP enhanced growth early in the fermentation, but at later stages the response of the mycelia to cAMP changed, and then cAMP inhibited growth. When citrate eventually began to accumulate cAMP augmented its sypthesis. The growth and acidogenic responses were quite specific to cAMP, and were sensitive to concentrations of about 1 muM. Cyclic AMP also either promoted or retarded the appearance of an unidentified yellow pigment. It is proposed that the growth and accumulating phases are distinct differentiated states, at least with respect to cAMP metabolism."}
{"id": "PMID:183885", "title": "A general survey of the proton spin-lattice relaxation-times of some oligo- and poly-saccharide derivatives.", "content": "A Fourier-transform method has been used to measure the spin-lattice relaxation-times (T1 values) of the anomeric protons of a selection of oligo- and poly-saccharide derivatives. Although systematic variations are found for the substances of lower molecular weight, these variations are essentially non-existent at higher molecular weights. Data for the disaccharides cellobiose, maltose, lactose, gentiobiose, and melibiose demonstrate that proton T1-values may provide a powerful method for evaluating conformations of oligosaccharides.", "contents": "A general survey of the proton spin-lattice relaxation-times of some oligo- and poly-saccharide derivatives. A Fourier-transform method has been used to measure the spin-lattice relaxation-times (T1 values) of the anomeric protons of a selection of oligo- and poly-saccharide derivatives. Although systematic variations are found for the substances of lower molecular weight, these variations are essentially non-existent at higher molecular weights. Data for the disaccharides cellobiose, maltose, lactose, gentiobiose, and melibiose demonstrate that proton T1-values may provide a powerful method for evaluating conformations of oligosaccharides."}
{"id": "PMID:183887", "title": "Concerning the independence of the basis of hypertension due to ACTH or renovascular constriction.", "content": "Administration of ACTH to four sheep with chronic renovascular hypertension resulted in an increase in blood pressure which was at least as high as that described in normotensive sheep and could be completely accounted for by an increase in cardiac output.", "contents": "Concerning the independence of the basis of hypertension due to ACTH or renovascular constriction. Administration of ACTH to four sheep with chronic renovascular hypertension resulted in an increase in blood pressure which was at least as high as that described in normotensive sheep and could be completely accounted for by an increase in cardiac output."}
{"id": "PMID:183889", "title": "Adenohypophysial cell-types in the pituitary gland of the soft-shelled turtle, Trionyx sinensis. I. Seasonal cycles.", "content": "By using various staining techniques, two acidophilic and three basophilic cell-types have been distinguished in the pars distalis of Trionyx sinensis. Seasonal fluctuations in their cytoplasmic granulation, cell and nuclear size have been compared with seasonal patterns of activity in the gonads, adrenals and thyroid. On the basis of the results, specific functions have been ascribed to each cell-type. Basophils 1 activity closely parallels the seasonal thyroid cycle. Basophils 2 are probably FSH-secreting gonadotropes and their activity correlates with the seasonal cycle of spermatogenesis in the seminiferous tubules. The functional activity of the testicular interstitial cells correlates with the secretory pattern of the basophils 3. That these are LH-secreting cells is also suggested by the epididymidal cycle, which indicates a high level of androgen secretion coincident with the rapid degranulation of these cells, at a time of no spermatogenetic activity. Adrenal activity shows no relationship with the basophils 3 cycle, and chromophobic cells may be the locus of ACTH secretion. Acidophils 2 remain stable throughout the year and are probably somatotropes, but acidophils 1 increase their activity in autumn and are likely to be lactotropes.", "contents": "Adenohypophysial cell-types in the pituitary gland of the soft-shelled turtle, Trionyx sinensis. I. Seasonal cycles. By using various staining techniques, two acidophilic and three basophilic cell-types have been distinguished in the pars distalis of Trionyx sinensis. Seasonal fluctuations in their cytoplasmic granulation, cell and nuclear size have been compared with seasonal patterns of activity in the gonads, adrenals and thyroid. On the basis of the results, specific functions have been ascribed to each cell-type. Basophils 1 activity closely parallels the seasonal thyroid cycle. Basophils 2 are probably FSH-secreting gonadotropes and their activity correlates with the seasonal cycle of spermatogenesis in the seminiferous tubules. The functional activity of the testicular interstitial cells correlates with the secretory pattern of the basophils 3. That these are LH-secreting cells is also suggested by the epididymidal cycle, which indicates a high level of androgen secretion coincident with the rapid degranulation of these cells, at a time of no spermatogenetic activity. Adrenal activity shows no relationship with the basophils 3 cycle, and chromophobic cells may be the locus of ACTH secretion. Acidophils 2 remain stable throughout the year and are probably somatotropes, but acidophils 1 increase their activity in autumn and are likely to be lactotropes."}
{"id": "PMID:183890", "title": "Ultrastructural and cytochemical features of SV 40 transformed hypothalamic cell lines.", "content": "A continuous cell line was previously obtained by Simian Virus (SV) 40 transformation of primary cultures of dissociated mouse fetal hypothalami. One clone from this cell line has been previously shown to possess some of the ultrastructural features, immunological properties and synthesizing capacities of magnocellular hypothalamic neurons which secrete vasopressin and neurophysins. The present paper reports on the morphological characterization of 14 other clones or subclones of the original cell line, using the following criteria: phase contrast microscopy, electron microscopy, Gomori's aldehyde fuchsin staining, cytochemical detection of beta-glucuronidase, immunochemical staining with antisera against bovine neurophysin I, bovine neurophysin II, lys-vasopressin, oxytocin, LH-RH and TRH. The results allowed the conclusion that the clones as well as the subclones can be distributed into two groups: 1) neurosecretory neurons which all possess several of the ultrastructural and cytochemical features of the neurophysin-vasopressin synthesizing clone, and 2) primitive nerve cells which are devoid of such features but display numerous bundles of filaments. In addition some clones were found to display intermediate features between groups 1 and 2. A similar diversity was observed within clones of the original strain and subclones of a neurosecretory clone. It is suggested that the primitive clones could represent precursors of the neurosecretory clones.", "contents": "Ultrastructural and cytochemical features of SV 40 transformed hypothalamic cell lines. A continuous cell line was previously obtained by Simian Virus (SV) 40 transformation of primary cultures of dissociated mouse fetal hypothalami. One clone from this cell line has been previously shown to possess some of the ultrastructural features, immunological properties and synthesizing capacities of magnocellular hypothalamic neurons which secrete vasopressin and neurophysins. The present paper reports on the morphological characterization of 14 other clones or subclones of the original cell line, using the following criteria: phase contrast microscopy, electron microscopy, Gomori's aldehyde fuchsin staining, cytochemical detection of beta-glucuronidase, immunochemical staining with antisera against bovine neurophysin I, bovine neurophysin II, lys-vasopressin, oxytocin, LH-RH and TRH. The results allowed the conclusion that the clones as well as the subclones can be distributed into two groups: 1) neurosecretory neurons which all possess several of the ultrastructural and cytochemical features of the neurophysin-vasopressin synthesizing clone, and 2) primitive nerve cells which are devoid of such features but display numerous bundles of filaments. In addition some clones were found to display intermediate features between groups 1 and 2. A similar diversity was observed within clones of the original strain and subclones of a neurosecretory clone. It is suggested that the primitive clones could represent precursors of the neurosecretory clones."}
{"id": "PMID:183891", "title": "A unique RNA species involved in initiation of vesicular stomatitis virus RNA transcription in vitro.", "content": "Purified virions of vesicular stomatitis virus (VSV) are capable of synthesizing two distinct types of virus-specific RNA in vitro. The first consists of several viral mRNAs which have been previously shown to contain the blocked 5' terminal sequence GpppApApCpApGp and 3' terminal poly(A). The second type of RNA has an unblocked 5' terminus and does not contain poly(A) stretches long enough to bind to oligo (dT)-cellulose columns. It migrates in 20% polyacrylamide gels as a single homogeneous peak with an estimated chain length of 68 nucleotides. Base analysis demonstrated that this small RNA molecule is composed of 48% AMP, 20% CMP, 11% GMP, and 21% UMP. The 5' terminal sequence of the small RNA is ppApCpGp, which appears to be complementary to the 3' terminal sequence of the VSV genome RNA (...PypGpU). These results indicate that this small RNA molecule probably represents the intitiated lead-in RNA segment which is removed during formation of VSV mRNAs by a possible processing mechanism.", "contents": "A unique RNA species involved in initiation of vesicular stomatitis virus RNA transcription in vitro. Purified virions of vesicular stomatitis virus (VSV) are capable of synthesizing two distinct types of virus-specific RNA in vitro. The first consists of several viral mRNAs which have been previously shown to contain the blocked 5' terminal sequence GpppApApCpApGp and 3' terminal poly(A). The second type of RNA has an unblocked 5' terminus and does not contain poly(A) stretches long enough to bind to oligo (dT)-cellulose columns. It migrates in 20% polyacrylamide gels as a single homogeneous peak with an estimated chain length of 68 nucleotides. Base analysis demonstrated that this small RNA molecule is composed of 48% AMP, 20% CMP, 11% GMP, and 21% UMP. The 5' terminal sequence of the small RNA is ppApCpGp, which appears to be complementary to the 3' terminal sequence of the VSV genome RNA (...PypGpU). These results indicate that this small RNA molecule probably represents the intitiated lead-in RNA segment which is removed during formation of VSV mRNAs by a possible processing mechanism."}
{"id": "PMID:183892", "title": "The number of superhelical turns in native virion SV40 DNA and minicol DNA determined by the band counting method.", "content": "By a method of overlapping the results obtained after agarose gel electrophoresis under two different sets of conditions, it has become possible to determine the number of superhelical turns in a given DNA by counting the bands present after partially relaxing the DNA (Keller and Wendel, 1974) with highly purified nicking-closing (N-C) enzyme from LA9 mouse cell nuclei. Because native supercoiled DNA is heterogeneous with respect to superhelix density, an average number of superhelical turns was determined. Virion SV40 DNA contains 26 +/- 0.5 superhelical turns, and native Minicol DNA contains 19 +/- 0.5 superhelical turns. The above are values at 0.2 M NaCl and at 37 degrees C, the condition under which the enzymatic relaxations were performed. The superhelix densities determined by the band counting method have been compared with superhelix densities determined by buoyant equilibrium in PDl-CsCl gradients. The Gray, Upholt, and Vinograd (1971) calculation procedure has been used for evaluating the superhelix densities by the latter method with the new statement, however, that relaxed DNA has zero superhelical turns. Comparison of the superhelix densities obtained by both methods permits a calculation of an unwinding angle for ethidium. The mean value from experiments with SV40 DNA is 23 +/- 3 degree. The average number of superhelical turns in SV40, 26, combined with the value, 21, obtained by both Griffith (1975) and Germond et al. (1975) for the average number of nucleosomes per SV40 genome, yields an average of 1.25 superhelical turns per 1/21 of the SV40 genome. If the regions of internucleosomal DNA are fully relaxed, 1.25 correesponds to the average number of superhelical turns with a nucleosome. When analyzed under identical conditions, the limit product generated by ligating a nicked circular substrate in the presence of 0.001 M Mg2+ at 37 degrees C (ligation conditions) is slightly more positively supercoiled than the limit product obtained when the N-C reaction is performed in 0.2 M NaCl at 37 degrees C. The difference in superhelix density as measured in gels between the two sets of limit products for both Minicol and SV40 DNAs is 0.0059 +/- 0.0005. This result indicates that the DNA duplex is overwound in the ligation solvent relative to its state in 0.2 M NaCl.", "contents": "The number of superhelical turns in native virion SV40 DNA and minicol DNA determined by the band counting method. By a method of overlapping the results obtained after agarose gel electrophoresis under two different sets of conditions, it has become possible to determine the number of superhelical turns in a given DNA by counting the bands present after partially relaxing the DNA (Keller and Wendel, 1974) with highly purified nicking-closing (N-C) enzyme from LA9 mouse cell nuclei. Because native supercoiled DNA is heterogeneous with respect to superhelix density, an average number of superhelical turns was determined. Virion SV40 DNA contains 26 +/- 0.5 superhelical turns, and native Minicol DNA contains 19 +/- 0.5 superhelical turns. The above are values at 0.2 M NaCl and at 37 degrees C, the condition under which the enzymatic relaxations were performed. The superhelix densities determined by the band counting method have been compared with superhelix densities determined by buoyant equilibrium in PDl-CsCl gradients. The Gray, Upholt, and Vinograd (1971) calculation procedure has been used for evaluating the superhelix densities by the latter method with the new statement, however, that relaxed DNA has zero superhelical turns. Comparison of the superhelix densities obtained by both methods permits a calculation of an unwinding angle for ethidium. The mean value from experiments with SV40 DNA is 23 +/- 3 degree. The average number of superhelical turns in SV40, 26, combined with the value, 21, obtained by both Griffith (1975) and Germond et al. (1975) for the average number of nucleosomes per SV40 genome, yields an average of 1.25 superhelical turns per 1/21 of the SV40 genome. If the regions of internucleosomal DNA are fully relaxed, 1.25 correesponds to the average number of superhelical turns with a nucleosome. When analyzed under identical conditions, the limit product generated by ligating a nicked circular substrate in the presence of 0.001 M Mg2+ at 37 degrees C (ligation conditions) is slightly more positively supercoiled than the limit product obtained when the N-C reaction is performed in 0.2 M NaCl at 37 degrees C. The difference in superhelix density as measured in gels between the two sets of limit products for both Minicol and SV40 DNAs is 0.0059 +/- 0.0005. This result indicates that the DNA duplex is overwound in the ligation solvent relative to its state in 0.2 M NaCl."}
{"id": "PMID:183893", "title": "5' terminal nucleotide sequences of the messenger RNA's of Dictyostelium discoideum.", "content": "As in the mRNA from all other eucaryotic cells examined, the 5' nucleotide in messenger RNA from Dictyostelium discoideum is linked by a 5'-5' triphosphate bridge to the unusual nucleoside 7-methyl guanosine. In mammalian cellular mRNA, the 5' terminal sequences have the general formula m7GpppXmpYp(m), where X and Y can be either purine or pyrimidine nucleotides and Y, as well as X, may contain a 2'0-methylated ribose. Although at least 32 5' terminal sequences are possible in cellular mRNA, only four are present in Dictyostelum mRNA. They are (I) m7GppppAp (65%); (II) m7GpppGp (10%); (III) m7GpppAmpAp (10%); (IV m7GpppAp (65%); (II) m7gpppGp (10%); (III) m7GpppAmpAp (10%); (IV) m7GpppAmpUp (10%). Sequences I and II are simpler than those previously reported for mammalian cells because they lack 2'0-methylated nucleosides. Another difference is that in all Dictyostelium mRNAs. the nucleoside X is a purine. The nucleoside 6-methyl adenosine which is found internal to the 5' end of the mRNA of mammalian cells is not detectable in Dictyostelium mRNA. Thus neither 2'0-methylated nucleotides nor 6-methyl adenosine can represent sites for processing of a primary nuclear transript to yield mRNA.", "contents": "5' terminal nucleotide sequences of the messenger RNA's of Dictyostelium discoideum. As in the mRNA from all other eucaryotic cells examined, the 5' nucleotide in messenger RNA from Dictyostelium discoideum is linked by a 5'-5' triphosphate bridge to the unusual nucleoside 7-methyl guanosine. In mammalian cellular mRNA, the 5' terminal sequences have the general formula m7GpppXmpYp(m), where X and Y can be either purine or pyrimidine nucleotides and Y, as well as X, may contain a 2'0-methylated ribose. Although at least 32 5' terminal sequences are possible in cellular mRNA, only four are present in Dictyostelum mRNA. They are (I) m7GppppAp (65%); (II) m7GpppGp (10%); (III) m7GpppAmpAp (10%); (IV m7GpppAp (65%); (II) m7gpppGp (10%); (III) m7GpppAmpAp (10%); (IV) m7GpppAmpUp (10%). Sequences I and II are simpler than those previously reported for mammalian cells because they lack 2'0-methylated nucleosides. Another difference is that in all Dictyostelium mRNAs. the nucleoside X is a purine. The nucleoside 6-methyl adenosine which is found internal to the 5' end of the mRNA of mammalian cells is not detectable in Dictyostelium mRNA. Thus neither 2'0-methylated nucleotides nor 6-methyl adenosine can represent sites for processing of a primary nuclear transript to yield mRNA."}
{"id": "PMID:183894", "title": "The effect of SV40 transformation on the chromosomal proteins of 3T3 mouse embryo fibroblasts.", "content": "The composition and metabolism of chromosomal proteins-histones and nonhistones chromosomal proteins-were examined in normal and SV40 transformed 3T3 mouse cells. Variations were observed, many of which were similar to those previously reported for normal and SV40 transformed W138 human diploid fibroblasts. The possible implications of these viral induced changes in the protein component of the genome for the phenotypic modifications which occur in transformed cells are discussed.", "contents": "The effect of SV40 transformation on the chromosomal proteins of 3T3 mouse embryo fibroblasts. The composition and metabolism of chromosomal proteins-histones and nonhistones chromosomal proteins-were examined in normal and SV40 transformed 3T3 mouse cells. Variations were observed, many of which were similar to those previously reported for normal and SV40 transformed W138 human diploid fibroblasts. The possible implications of these viral induced changes in the protein component of the genome for the phenotypic modifications which occur in transformed cells are discussed."}
{"id": "PMID:183903", "title": "Evidence for superoxide-dependent reduction of Fe3+ and its role in enzyme-generated hydroxyl radical formation.", "content": "This report describes studies yielding additional evidence that superoxide anion (O2) production by some biological oxidoreductase systems is a potential source of hydroxyl radical production. The phenomenon appears to be an intrinsic property of certain enzyme systems which produce superoxide and H2O2, and can result in extensive oxidative degradation of membrane lipids. Earlier studies had suggested that iron (chelated to maintain solubility) augmented production of the hydroxyl radical in such systems according to the following reaction sequence: O2 + Fe3+ leads to O2 + Fe2+ Fe2+ + H2O2 leads to Fe3+ + HO-+OH-. The data reported below provide additional support for the occurrence of these reactions, especially the reduction of Fe3+ by superoxide. Because the conditions for such reactions appear to exist in animal tissues, the results indicate a mechanism for the initiation and promotion of peroxidative attacks on membrane lipids and also suggest that the role of antioxidants in intracellular metabolism may be to inhibit initiation of degradative reactions by the highly reactive radicals formed extraneously during metabolic activity. This report presents the following new information: (1) Fe3+ is reduced to Fe2+ during xanthine oxidase activity and a significant part of the reduction was oxygen dependent. (2) Mn2+ appears to function as an efficient superoxide anion scavenger, and this function can be inhibited by EDTA. (3) The O2-dependent reduction of Fe3+ to Fe2+ by xanthine oxidase activity is inhibited by Mn2+, which, in view of statement 2 above, is a further indication that the reduction of the iron involves superoxide anion. (4) Free radical scavengers prevent or reverse the Fe3+ inhibiton of cytochrome c3+ reduction by xanthine oxidase. (5) The inhibition of xanthine oxidase-catalyzed reduction of cyt c3+ by Fe3+ does not affect uric acid production by the xanthine oxidase system. (6) The reoxidation of reduced cyt c in the xanthine oxidase system is markedly enhanced by Fe3+ and is apparently due to enhanced HO-RADICAL formation since the Fe3+-stimulated reoxidation is inhibited by free radical scavengers, including those with specificity for the hydroxyl radical.", "contents": "Evidence for superoxide-dependent reduction of Fe3+ and its role in enzyme-generated hydroxyl radical formation. This report describes studies yielding additional evidence that superoxide anion (O2) production by some biological oxidoreductase systems is a potential source of hydroxyl radical production. The phenomenon appears to be an intrinsic property of certain enzyme systems which produce superoxide and H2O2, and can result in extensive oxidative degradation of membrane lipids. Earlier studies had suggested that iron (chelated to maintain solubility) augmented production of the hydroxyl radical in such systems according to the following reaction sequence: O2 + Fe3+ leads to O2 + Fe2+ Fe2+ + H2O2 leads to Fe3+ + HO-+OH-. The data reported below provide additional support for the occurrence of these reactions, especially the reduction of Fe3+ by superoxide. Because the conditions for such reactions appear to exist in animal tissues, the results indicate a mechanism for the initiation and promotion of peroxidative attacks on membrane lipids and also suggest that the role of antioxidants in intracellular metabolism may be to inhibit initiation of degradative reactions by the highly reactive radicals formed extraneously during metabolic activity. This report presents the following new information: (1) Fe3+ is reduced to Fe2+ during xanthine oxidase activity and a significant part of the reduction was oxygen dependent. (2) Mn2+ appears to function as an efficient superoxide anion scavenger, and this function can be inhibited by EDTA. (3) The O2-dependent reduction of Fe3+ to Fe2+ by xanthine oxidase activity is inhibited by Mn2+, which, in view of statement 2 above, is a further indication that the reduction of the iron involves superoxide anion. (4) Free radical scavengers prevent or reverse the Fe3+ inhibiton of cytochrome c3+ reduction by xanthine oxidase. (5) The inhibition of xanthine oxidase-catalyzed reduction of cyt c3+ by Fe3+ does not affect uric acid production by the xanthine oxidase system. (6) The reoxidation of reduced cyt c in the xanthine oxidase system is markedly enhanced by Fe3+ and is apparently due to enhanced HO-RADICAL formation since the Fe3+-stimulated reoxidation is inhibited by free radical scavengers, including those with specificity for the hydroxyl radical."}
{"id": "PMID:183904", "title": "[Rare non-functioning insular tumor of the pancreas].", "content": "A case of cystic neoplasia with a cephalopancreatic localization, arising in a young woman aged 26 and derived from the beta-insular elements, is presented. The tumour had invaded the porto-mesenteric tract, and hence duodenopancreatic demolition had to be followed by venous repair by prosthesis. On the basis of the literature the biological complexity of this exceptional tumour is disscussed (especially in relation to prognosis), as well as the surgical treatment adopted in this patient, who is in excellent conditions more than three years later.", "contents": "[Rare non-functioning insular tumor of the pancreas]. A case of cystic neoplasia with a cephalopancreatic localization, arising in a young woman aged 26 and derived from the beta-insular elements, is presented. The tumour had invaded the porto-mesenteric tract, and hence duodenopancreatic demolition had to be followed by venous repair by prosthesis. On the basis of the literature the biological complexity of this exceptional tumour is disscussed (especially in relation to prognosis), as well as the surgical treatment adopted in this patient, who is in excellent conditions more than three years later."}
{"id": "PMID:183908", "title": "Susceptibility of some rodent species to monkeypox virus, and course of the infection.", "content": "The authors studied the susceptibility of five species of rodent to monkeypox virus inoculated by various routes and the course of the infection. Reactions varied from complete resistance to lethal generalized infection with rash. Rabbits and white mice appeared to be the most susceptible species and young animals were more susceptible than adults. Monkeypox virus was found to infect young animals by natural routes, i.e., per os and intranasally. Transmission by contact occurred among 10-day-old rabbits. Since antibodies to monkeypox virus may persist for over a year in the sera of convalescent animals, serological examination of animals is recommended for studying the ecology of this virus.", "contents": "Susceptibility of some rodent species to monkeypox virus, and course of the infection. The authors studied the susceptibility of five species of rodent to monkeypox virus inoculated by various routes and the course of the infection. Reactions varied from complete resistance to lethal generalized infection with rash. Rabbits and white mice appeared to be the most susceptible species and young animals were more susceptible than adults. Monkeypox virus was found to infect young animals by natural routes, i.e., per os and intranasally. Transmission by contact occurred among 10-day-old rabbits. Since antibodies to monkeypox virus may persist for over a year in the sera of convalescent animals, serological examination of animals is recommended for studying the ecology of this virus."}
{"id": "PMID:183909", "title": "Two levels of resting potential in canine cardiac Purkinje fibers exposed to sodium-free solutions.", "content": "Canine cardiac Purkinje fibers exposed to sodium-free solutions containing 16 mM CaCl2, 20 mM tetraethylammonium chloride, 108 mM tetramethylammonium chloride, and 2.7 mM KCl may be quiescent at a resting potential of either -50 mV or -90 mV. The membrane potential of these fibers can be switched from -50 mV to -90 mV by a hyperpolarizing current pulse and from -90 mV to -50 mV by a depolarizing current pulse. The transition from -50 mV to -90 mV depends on a voltage-dependent increase in potassium conductance, that conductance being low at -50 mV and high at -90 mV. A reduction in potassium conductance causes the fiber to depolarize from -90 mV to -50 mV because of the presence of an inward current which apparently is carried mainly by Ca. Fibers that show a high resting potential cannot be excited except by depolarizing stimuli strong enough to move the membrane from -90 mV to a threshold potential of about -40 mV. Fibers that show a low resting potential are more easily excited and may show rhythmic activity sustained by afterpotentials that appear only if the low membrane potential is accompanied by a low potassium conductance. Slow changes in membrane potential also are seen; these changes may result from movements of chloride.", "contents": "Two levels of resting potential in canine cardiac Purkinje fibers exposed to sodium-free solutions. Canine cardiac Purkinje fibers exposed to sodium-free solutions containing 16 mM CaCl2, 20 mM tetraethylammonium chloride, 108 mM tetramethylammonium chloride, and 2.7 mM KCl may be quiescent at a resting potential of either -50 mV or -90 mV. The membrane potential of these fibers can be switched from -50 mV to -90 mV by a hyperpolarizing current pulse and from -90 mV to -50 mV by a depolarizing current pulse. The transition from -50 mV to -90 mV depends on a voltage-dependent increase in potassium conductance, that conductance being low at -50 mV and high at -90 mV. A reduction in potassium conductance causes the fiber to depolarize from -90 mV to -50 mV because of the presence of an inward current which apparently is carried mainly by Ca. Fibers that show a high resting potential cannot be excited except by depolarizing stimuli strong enough to move the membrane from -90 mV to a threshold potential of about -40 mV. Fibers that show a low resting potential are more easily excited and may show rhythmic activity sustained by afterpotentials that appear only if the low membrane potential is accompanied by a low potassium conductance. Slow changes in membrane potential also are seen; these changes may result from movements of chloride."}
{"id": "PMID:183910", "title": "Origin of epicardial ST-T wave potentials in the intact dog.", "content": "Ventricular repolarization was analyzed by measuring epicardial potential distributions in intact dogs with single or multiple ectopic foci and a minimum at the terminal site(s) of excitation. During the latter half of the T wave the distributions became more complex, and two maxima evolved from the initial one at each ectopic site. The measured epicardial potentials were simulated by means of a model of ST-T wave events that is suitable for study of single and multiple ectopic beats with fusion, a a model we call 'SI model.' Intracellular potentials around the ventricles during repolarization were calculated from measured excitation sequences and known action potential shapes. The extracellular potentials around the ventricles were computed from the intracellular ones by a simplified ventricular geometry. The satisfactory agreement between the theoretical and measured extracellular potential distribution shows that the complex changes which occur throughout the ST-T wave are predicted well on the basis of changes in the intracellular potential distributions. In contrast to the well known lability of the T wave from beat, the results show that for any single beat the events of repolarization proceed in an entirely repeatable and deterministic fashion. The results present a way to directly represent cardiac extracellular events during the ST-T wave, a method analogous to the use of isochromes during QRS, and they imply that in the future it will by possible to achieve a more precise quantitative understanding of the events of the ST-T wave than thus far has been possible for QRS.", "contents": "Origin of epicardial ST-T wave potentials in the intact dog. Ventricular repolarization was analyzed by measuring epicardial potential distributions in intact dogs with single or multiple ectopic foci and a minimum at the terminal site(s) of excitation. During the latter half of the T wave the distributions became more complex, and two maxima evolved from the initial one at each ectopic site. The measured epicardial potentials were simulated by means of a model of ST-T wave events that is suitable for study of single and multiple ectopic beats with fusion, a a model we call 'SI model.' Intracellular potentials around the ventricles during repolarization were calculated from measured excitation sequences and known action potential shapes. The extracellular potentials around the ventricles were computed from the intracellular ones by a simplified ventricular geometry. The satisfactory agreement between the theoretical and measured extracellular potential distribution shows that the complex changes which occur throughout the ST-T wave are predicted well on the basis of changes in the intracellular potential distributions. In contrast to the well known lability of the T wave from beat, the results show that for any single beat the events of repolarization proceed in an entirely repeatable and deterministic fashion. The results present a way to directly represent cardiac extracellular events during the ST-T wave, a method analogous to the use of isochromes during QRS, and they imply that in the future it will by possible to achieve a more precise quantitative understanding of the events of the ST-T wave than thus far has been possible for QRS."}
{"id": "PMID:183911", "title": "A comparison of aortic baroreceptor discharge in normotensive and spontaneously hypertensive rats.", "content": "Electrophysiological characteristics of individual aortic baroreceptors from normotensive rats (NTR) and spontaneously hypertensive rats (SHR) were compared. Impulse activity of afferent fibers was examined following the application of pressure steps to an in vitro aortic arch-aortic nerve preparation. Thirty-one fibers including seven unmyelinated fibers were studied completely over the range of 0-260 mm Hg, using steps 1-30 seconds in duration. The pressure threshold for peak transient discharge of baroreceptors of SHR's was 88.4 +/- 10.1 (mean +/- SE) mm Hg, whereas for baroreceptors of NTR's it was 77.5 +/- 9.3 mm Hg. The pressure threshold for steady state discharge was 137.3 +/- 5.2 mm Hg for SHR baroreceptors and 103.5 +/- 7.1 for NTR baroreceptors. These values compare favorably to measurements in vivo in the rat. The relationship between peak transient impulse frequency and pressure was linear, whereas the relationship between steady state impulse frequency and pressure was hyperbolic. The curvature of the steady state frequency-pressure curves was significantly reduced for baroreceptors of SHR's. The steady state pressure-volume curves of the aortas of SHR's and NTR's were similar, so that a reduction in distensibility could not account for the larger, significant differences in threshhold and sensitivity. Therefore resetting cannot be attributed simply to reduced vascular compliance.", "contents": "A comparison of aortic baroreceptor discharge in normotensive and spontaneously hypertensive rats. Electrophysiological characteristics of individual aortic baroreceptors from normotensive rats (NTR) and spontaneously hypertensive rats (SHR) were compared. Impulse activity of afferent fibers was examined following the application of pressure steps to an in vitro aortic arch-aortic nerve preparation. Thirty-one fibers including seven unmyelinated fibers were studied completely over the range of 0-260 mm Hg, using steps 1-30 seconds in duration. The pressure threshold for peak transient discharge of baroreceptors of SHR's was 88.4 +/- 10.1 (mean +/- SE) mm Hg, whereas for baroreceptors of NTR's it was 77.5 +/- 9.3 mm Hg. The pressure threshold for steady state discharge was 137.3 +/- 5.2 mm Hg for SHR baroreceptors and 103.5 +/- 7.1 for NTR baroreceptors. These values compare favorably to measurements in vivo in the rat. The relationship between peak transient impulse frequency and pressure was linear, whereas the relationship between steady state impulse frequency and pressure was hyperbolic. The curvature of the steady state frequency-pressure curves was significantly reduced for baroreceptors of SHR's. The steady state pressure-volume curves of the aortas of SHR's and NTR's were similar, so that a reduction in distensibility could not account for the larger, significant differences in threshhold and sensitivity. Therefore resetting cannot be attributed simply to reduced vascular compliance."}
{"id": "PMID:183912", "title": "Inhibition of adrenergic neurotransmission in canine vascular smooth muscle by histamine: mediation by H2-receptors.", "content": "Histamine depressed the contractions of dog saphenous vein strips caused by stimulation of their sympathetic nerves. This was due to a decrease in the release of norepinephrine which appears to be mediated by histamine H2-receptors. The evidence for this is as follows: (1) Contractions of the strips caused by activating the nerve endings electrically or by depolarization with potassium ions were depressed by histamine, whereas contractions caused by tyramine and norepinephrine were either unchanged or augmented. (2) Strips were incubated with norepinephrine[7-3H] and mounted for superfusion and isometric tension recording. The perfusate was collected for estimation of total radioactivity and for column chromatographic separation of norpinephrine and its metabolites. Histamine (0.9 muM) depressed the release of norepinphrine[7-3H] during contractions caused by electric stimulation, whereas the release of radioactive compounds caused by tyramine was unaffected. (3) The depression by histamine of the contractions and the efflux of radioactive compounds caused by electric stimulation were inhibited by an H2-receptor antagonist (metiamide), but were unaffected by an H1-receptor antagonist (pyrilamine). (4) Contractions caused by electric stimulation were inhibited by an H2-receptor agonist (4-methylhistamine) and augmented by an H1-receptor agonist (2-methylhistamine). These findings suggest the possibility that histamine, which is abundant in sympathetic nerves, might have a regulatory role in the release of the neurotransmitter.", "contents": "Inhibition of adrenergic neurotransmission in canine vascular smooth muscle by histamine: mediation by H2-receptors. Histamine depressed the contractions of dog saphenous vein strips caused by stimulation of their sympathetic nerves. This was due to a decrease in the release of norepinephrine which appears to be mediated by histamine H2-receptors. The evidence for this is as follows: (1) Contractions of the strips caused by activating the nerve endings electrically or by depolarization with potassium ions were depressed by histamine, whereas contractions caused by tyramine and norepinephrine were either unchanged or augmented. (2) Strips were incubated with norepinephrine[7-3H] and mounted for superfusion and isometric tension recording. The perfusate was collected for estimation of total radioactivity and for column chromatographic separation of norpinephrine and its metabolites. Histamine (0.9 muM) depressed the release of norepinphrine[7-3H] during contractions caused by electric stimulation, whereas the release of radioactive compounds caused by tyramine was unaffected. (3) The depression by histamine of the contractions and the efflux of radioactive compounds caused by electric stimulation were inhibited by an H2-receptor antagonist (metiamide), but were unaffected by an H1-receptor antagonist (pyrilamine). (4) Contractions caused by electric stimulation were inhibited by an H2-receptor agonist (4-methylhistamine) and augmented by an H1-receptor agonist (2-methylhistamine). These findings suggest the possibility that histamine, which is abundant in sympathetic nerves, might have a regulatory role in the release of the neurotransmitter."}
{"id": "PMID:183913", "title": "Intact vesicles of canine cardiac sarcolemma: evidence from vectorial properties of Na+, K+-ATPase.", "content": "Most biological membranes are functionally asymmetric. To study biochemical control of cardiac transsarcolemmalion fluxes, it would be of obvious advantage to use isolated vesicles of sarcolemma which retains the low passive permeability characteristics of intact sarcolemma because in such vesicles the membrane should exhibit its normal asymmetric character with respect to enzymic activities. The purpose of this investigation was to attempt identify such vesicles in a cardiac microsomal (membrane vesicular) preparation. We studied activation by Na+ and K+ of Na+, K+-ATPase and its associated K+-phosphatase activities, using as substrates ATP or p-nitrophenylphosphate (pNPP) in the presence of Mg2+. Optimal concentrations of K+ alone (10 mM) stimulated p-nitrophenylphosphatase (pNPPase) activity 1.8-fold, and over 80% of the increase could be inhibited by ouabain. Optimal Na+ plus K+ concentrations (100 mM and 10 mM, respectively) stimulated the rate of ATP hydrolysis 2-fold, but only 11 +/- 1.1% of the increased activity was ouabain-sensitive. Optimal pretreatment with sodium dodecyl sulfate (SDS) (0.3 mg/ml) rendered both activities completely sensitive to inhibition by ouabain and reduced the basal Mg2+-ATPase activity by 70-90%. The K+-stimulated pNPPase activity doubled after preincubation in SDS, but the ATPase activity stimulated by Na+ plus K+ fell by 50% under these conditions. A similar pattern of apparent activation was produced by preincubation with deoxycholate (DOC), except that basal Mg2+-dependent activities were resistant to destruction by this detergent. The incremental responses to activation by ions and substrates, and inhibition by oubain, are consistent with the hypothesis that permeability-intact vesicles of sarcolemma are present in the isolated preparation, and that detergent activation renders the vesicles highly permeable to the ions, substrates, and ouabain.", "contents": "Intact vesicles of canine cardiac sarcolemma: evidence from vectorial properties of Na+, K+-ATPase. Most biological membranes are functionally asymmetric. To study biochemical control of cardiac transsarcolemmalion fluxes, it would be of obvious advantage to use isolated vesicles of sarcolemma which retains the low passive permeability characteristics of intact sarcolemma because in such vesicles the membrane should exhibit its normal asymmetric character with respect to enzymic activities. The purpose of this investigation was to attempt identify such vesicles in a cardiac microsomal (membrane vesicular) preparation. We studied activation by Na+ and K+ of Na+, K+-ATPase and its associated K+-phosphatase activities, using as substrates ATP or p-nitrophenylphosphate (pNPP) in the presence of Mg2+. Optimal concentrations of K+ alone (10 mM) stimulated p-nitrophenylphosphatase (pNPPase) activity 1.8-fold, and over 80% of the increase could be inhibited by ouabain. Optimal Na+ plus K+ concentrations (100 mM and 10 mM, respectively) stimulated the rate of ATP hydrolysis 2-fold, but only 11 +/- 1.1% of the increased activity was ouabain-sensitive. Optimal pretreatment with sodium dodecyl sulfate (SDS) (0.3 mg/ml) rendered both activities completely sensitive to inhibition by ouabain and reduced the basal Mg2+-ATPase activity by 70-90%. The K+-stimulated pNPPase activity doubled after preincubation in SDS, but the ATPase activity stimulated by Na+ plus K+ fell by 50% under these conditions. A similar pattern of apparent activation was produced by preincubation with deoxycholate (DOC), except that basal Mg2+-dependent activities were resistant to destruction by this detergent. The incremental responses to activation by ions and substrates, and inhibition by oubain, are consistent with the hypothesis that permeability-intact vesicles of sarcolemma are present in the isolated preparation, and that detergent activation renders the vesicles highly permeable to the ions, substrates, and ouabain."}
{"id": "PMID:183914", "title": "Experimental myocardial ischemia: dynamic alterations in ventricular contractility and relaxation with dissociation of speed and force in the isovolumic dog heart.", "content": "Although the time course of changes in myocardial function during ischemia has been demonstrated for the papillary muscle, this time course in the intact heart is less well understood. Accordingly, in 24 isolated, isovolumic, perfused dog hearts, coronary perfusion pressure (PP) was lowered to various fixed levels. Left ventricular developed pressure (LVP) rapidly fell and reached 63 +/- 3% of control at 1 minute of ischemia 50 +/- 5% at 6 minutes; this was due primarily to an abbreviation of time to peak tension (TPP). dP/dt was 70 +/- 3% of control at 1 minute and 56 +/- 5% at 6 minutes. The rate of relaxation as reflected by negative dP/dt declined as well to 49 +/- 4% of control at 1 minute of ischemia and to 41 +/- 4% control at 6 minutes. These changes were directly correlated with the decrease in PP. When PP was restored to normal, an overshoot of LVP and dP/dt was noted, peaking at 1 minute, returning to control by 5 minutes, and then gradually declining to 90 +/- 2% of control following 25 minutes of recovery. Depression of the rate of relaxation was reduced, but persisted throughout recovery. Diminution of force development early in ishcemia is due primarily to decreased duration of contraction accompanied by a decrease in relaxation rate. Later, the rate of force development also falls, but some preservation of force development may result from the return toward normal of the duration of contraction.", "contents": "Experimental myocardial ischemia: dynamic alterations in ventricular contractility and relaxation with dissociation of speed and force in the isovolumic dog heart. Although the time course of changes in myocardial function during ischemia has been demonstrated for the papillary muscle, this time course in the intact heart is less well understood. Accordingly, in 24 isolated, isovolumic, perfused dog hearts, coronary perfusion pressure (PP) was lowered to various fixed levels. Left ventricular developed pressure (LVP) rapidly fell and reached 63 +/- 3% of control at 1 minute of ischemia 50 +/- 5% at 6 minutes; this was due primarily to an abbreviation of time to peak tension (TPP). dP/dt was 70 +/- 3% of control at 1 minute and 56 +/- 5% at 6 minutes. The rate of relaxation as reflected by negative dP/dt declined as well to 49 +/- 4% of control at 1 minute of ischemia and to 41 +/- 4% control at 6 minutes. These changes were directly correlated with the decrease in PP. When PP was restored to normal, an overshoot of LVP and dP/dt was noted, peaking at 1 minute, returning to control by 5 minutes, and then gradually declining to 90 +/- 2% of control following 25 minutes of recovery. Depression of the rate of relaxation was reduced, but persisted throughout recovery. Diminution of force development early in ishcemia is due primarily to decreased duration of contraction accompanied by a decrease in relaxation rate. Later, the rate of force development also falls, but some preservation of force development may result from the return toward normal of the duration of contraction."}
{"id": "PMID:183915", "title": "Relationships between myocardial perfusion, myocardial necrosis, and technetium--99m pyrophosphate uptake in dogs subjected to sudden coronary occlusion.", "content": "The quantitative relationship between abnormalities seen on technetium-99m pyrophosphate (99mTc-PYP) infarct scintigrams and the size of the myocardial infarction is unclear. We evaluated two possible determinants of 99mTc-PYP accumulation: myocardial perfusion measured with 7-10 mu microspheres and the extent of necrosis determined histologically. Hemodynamics and myocardial perfusion to small segments of the left ventricle were measured prior to, 5-10 min, and 44-48 hours following sudden occlusion of the left anterior descending coronary artery in ten awake dogs. 99mTc-PYP was injected i.v. following the third injection of microspheres and the animals were killed 2 hours later. The important findings were as follows: 1) there is a close relationship between the extent of myocardial necrosis observed and the perfusion of segments 5-10 min following coronary occlusion; and 2) that segmental myocardial perfusion is an important determinant of 99mTc-PYP accumulation by myocardial segments which contain areas of necrosis. Although the present data preclude statistical analysis of the relationship between the level of necrosis in a segment and the accumulation of 99mTc-PYP by that segment, the two do not appear to be related, a finding which would discourage use of intensity of 99mTc-PYP images for infarct size. The distribution of an abnormality on the scintigram may provide an estimate of infarct size. However, the geometry of the infarct and the resolving power of the scanning equipment will significantly limit this in many clinical situations.", "contents": "Relationships between myocardial perfusion, myocardial necrosis, and technetium--99m pyrophosphate uptake in dogs subjected to sudden coronary occlusion. The quantitative relationship between abnormalities seen on technetium-99m pyrophosphate (99mTc-PYP) infarct scintigrams and the size of the myocardial infarction is unclear. We evaluated two possible determinants of 99mTc-PYP accumulation: myocardial perfusion measured with 7-10 mu microspheres and the extent of necrosis determined histologically. Hemodynamics and myocardial perfusion to small segments of the left ventricle were measured prior to, 5-10 min, and 44-48 hours following sudden occlusion of the left anterior descending coronary artery in ten awake dogs. 99mTc-PYP was injected i.v. following the third injection of microspheres and the animals were killed 2 hours later. The important findings were as follows: 1) there is a close relationship between the extent of myocardial necrosis observed and the perfusion of segments 5-10 min following coronary occlusion; and 2) that segmental myocardial perfusion is an important determinant of 99mTc-PYP accumulation by myocardial segments which contain areas of necrosis. Although the present data preclude statistical analysis of the relationship between the level of necrosis in a segment and the accumulation of 99mTc-PYP by that segment, the two do not appear to be related, a finding which would discourage use of intensity of 99mTc-PYP images for infarct size. The distribution of an abnormality on the scintigram may provide an estimate of infarct size. However, the geometry of the infarct and the resolving power of the scanning equipment will significantly limit this in many clinical situations."}
{"id": "PMID:183916", "title": "Evaluation of a serum protein in pregnant rats.", "content": "The increase of a serum protein in the circulation of rats during pregnancy has been described. The protein is different from the human pregnancy zone protein previously described. This new serum protein factor is present in normal rat serum and accounts for approximately 1% of the total serum protein. The protein factor disappears from the serum of animals bearing Morris hepatomas 7777 and 7800. The amount of factor diminishes as the tumors increase in size. The levels of this protein in the serum increased several fold during pregnancy with highest levels found shortly before parturition. Levels remained elevated for at least 12 days post partum. No corresponding increase in the levels of this serum factor in the fetal circulation was observed. Increased levels in the maternal circulation were due to an increased synthesis of this serum protein during pregnancy. A corresponding band was observed on polyacrylamide gels for normal human female and pregnant human sera or plasma. However, there was no increase during pregnancy as judged by polyacrylamide gel electrophoresis. Quantitative determination of the protein in human sera was not possible since the band corresponding to the serum protein in rats did not cross react with a rabbit anti-rat serum factor.", "contents": "Evaluation of a serum protein in pregnant rats. The increase of a serum protein in the circulation of rats during pregnancy has been described. The protein is different from the human pregnancy zone protein previously described. This new serum protein factor is present in normal rat serum and accounts for approximately 1% of the total serum protein. The protein factor disappears from the serum of animals bearing Morris hepatomas 7777 and 7800. The amount of factor diminishes as the tumors increase in size. The levels of this protein in the serum increased several fold during pregnancy with highest levels found shortly before parturition. Levels remained elevated for at least 12 days post partum. No corresponding increase in the levels of this serum factor in the fetal circulation was observed. Increased levels in the maternal circulation were due to an increased synthesis of this serum protein during pregnancy. A corresponding band was observed on polyacrylamide gels for normal human female and pregnant human sera or plasma. However, there was no increase during pregnancy as judged by polyacrylamide gel electrophoresis. Quantitative determination of the protein in human sera was not possible since the band corresponding to the serum protein in rats did not cross react with a rabbit anti-rat serum factor."}
{"id": "PMID:183917", "title": "A comparison of methods for the immunoassay of serum apolipoprotein B in man.", "content": "Three assays for serum apolipoprotein B, radioimmunoassay, automated immunoprecipitation and rocket immunoelectrophoresis were compared. The antiserum used was raised against lipoprotein of density 1.040-1.053 g/ml (lipoprotein B). Each of the methods had a high degree of specificity when tested against potential interfering substances. The lowest levels of apolipoprotein B could be measured with radioimmunoassay but this sensitivity entailed the use of high dilutions of serum and resulted in a lower precision. Concentration response curves of lipoprotein B solution and serum were parallel for radioimmunoassay and automated immunoprecipitation but were not for rocket immunoelectrophoresis. Serum apolipoprotein B could be assayed by immunoelectrophoresis, however, if serum calibrated against the protein concentration of lipoprotein B solution by either of the other two methods was used as a secondary standard. Such a secondary serum standard also proved advantageous for all the methods because of the relative stability of the apolipoprotein B content of serum as compared to aqueous solutions of lipoprotein B. The mean apolipoprotein B concentration in 29 normolipaemic subjects aged 20-30 years was 0.84 +/- 0.12 g/1 (mean +/- S.D.) by radioimmunoassay, 0.85 +/- 0.11 g/1 by automated immunoprecipitation and 0.88 +/- 0.11 g/1 by rocket immunoelectrophoresis. The correlation between apolipoprotein B levels measured by the three methods was good. The ratio of serum cholesterol to serum apolipoprotein B was unaffected by individual differences in serum cholesterol or triglyceride levels. There was no significant difference between fasting and post-prandial serum apolipoprotein B concentrations. Radioimmunoassay is particularly suited to the measurement of low levels of apolipoprotein B, automated immunoprecipitation for large numbers of samples and rocket immunoelectrophoresis, when care is taken in the interpretation of results, for small numbers of samples.", "contents": "A comparison of methods for the immunoassay of serum apolipoprotein B in man. Three assays for serum apolipoprotein B, radioimmunoassay, automated immunoprecipitation and rocket immunoelectrophoresis were compared. The antiserum used was raised against lipoprotein of density 1.040-1.053 g/ml (lipoprotein B). Each of the methods had a high degree of specificity when tested against potential interfering substances. The lowest levels of apolipoprotein B could be measured with radioimmunoassay but this sensitivity entailed the use of high dilutions of serum and resulted in a lower precision. Concentration response curves of lipoprotein B solution and serum were parallel for radioimmunoassay and automated immunoprecipitation but were not for rocket immunoelectrophoresis. Serum apolipoprotein B could be assayed by immunoelectrophoresis, however, if serum calibrated against the protein concentration of lipoprotein B solution by either of the other two methods was used as a secondary standard. Such a secondary serum standard also proved advantageous for all the methods because of the relative stability of the apolipoprotein B content of serum as compared to aqueous solutions of lipoprotein B. The mean apolipoprotein B concentration in 29 normolipaemic subjects aged 20-30 years was 0.84 +/- 0.12 g/1 (mean +/- S.D.) by radioimmunoassay, 0.85 +/- 0.11 g/1 by automated immunoprecipitation and 0.88 +/- 0.11 g/1 by rocket immunoelectrophoresis. The correlation between apolipoprotein B levels measured by the three methods was good. The ratio of serum cholesterol to serum apolipoprotein B was unaffected by individual differences in serum cholesterol or triglyceride levels. There was no significant difference between fasting and post-prandial serum apolipoprotein B concentrations. Radioimmunoassay is particularly suited to the measurement of low levels of apolipoprotein B, automated immunoprecipitation for large numbers of samples and rocket immunoelectrophoresis, when care is taken in the interpretation of results, for small numbers of samples."}
{"id": "PMID:183918", "title": "Zero electrophoretic mobility of very low density lipoproteins in type III hyperlipidemic patients during treatment.", "content": "In some cases of type III hyperlipoproteinemia reduction of lipid levels by diet and/or drugs results in a complete loss of mobility of the VLDL fraction on paper electrophoresis.", "contents": "Zero electrophoretic mobility of very low density lipoproteins in type III hyperlipidemic patients during treatment. In some cases of type III hyperlipoproteinemia reduction of lipid levels by diet and/or drugs results in a complete loss of mobility of the VLDL fraction on paper electrophoresis."}
{"id": "PMID:183919", "title": "The separation of plasma lipoproteins using gel electrofocusing and polyacrylamide gradient gel electrophoresis.", "content": "Polyacrylamide gel electrofocusing and gradient electrophoresis have been used to separate the lipoproteins in whole plasma and in fractions prepared by sequential flotation in the ultracentrifuge and by precipitation with dextran sulphate and manganous chloride. After the two-dimensional separation, high density lipoproteins appear as a zone showing noticeable heterogeneity with respect to both isoelectric point and molecular weight. Low density lipoproteins are resolved as a compact spot while very low density lipoproteins are visible as a long horizontal streak across the top of the electrophoresis gel. The implications of the technique for the analysis of lipoprotein patterns in pathological plasmas are discussed.", "contents": "The separation of plasma lipoproteins using gel electrofocusing and polyacrylamide gradient gel electrophoresis. Polyacrylamide gel electrofocusing and gradient electrophoresis have been used to separate the lipoproteins in whole plasma and in fractions prepared by sequential flotation in the ultracentrifuge and by precipitation with dextran sulphate and manganous chloride. After the two-dimensional separation, high density lipoproteins appear as a zone showing noticeable heterogeneity with respect to both isoelectric point and molecular weight. Low density lipoproteins are resolved as a compact spot while very low density lipoproteins are visible as a long horizontal streak across the top of the electrophoresis gel. The implications of the technique for the analysis of lipoprotein patterns in pathological plasmas are discussed."}
{"id": "PMID:183920", "title": "Urate production in heterozygotes for glucose-6-phosphatase deficiency.", "content": "Urate production and excretion were studied in heterozygous parents of a child with glucose-6-phosphatase deficiency. Both parents demonstrated glucose-6-phosphatase concentrations in platelets intermediate between those in the homozygote and the normal. The miscible urate pool and turnover rate, the rate of incorporation of [14C]glycine into urate, the renal clearance of urate and the percentage excretion of labelled urate by the renal route were within the normal range in both heterozygotes, as were the serum cholesterol and triglyceride concentrations. Thus, a partial deficiency of glucose-6-phosphatase was not associated with the abnormalities of urate or lipoprotein metabolism which are features of homozygous glucose-6-phosphatase deficiency. Erythrocyte phosphoribosyl-pyrophosphate concentration, an increased concentration of which has been postulated as the mechanism responsible for the increased de novo purine biosynthesis in glucose-6-phosphatase deficiency, was found to be within the normal range in erythrocytes from both a homozygote and a heterozygote for this condition.", "contents": "Urate production in heterozygotes for glucose-6-phosphatase deficiency. Urate production and excretion were studied in heterozygous parents of a child with glucose-6-phosphatase deficiency. Both parents demonstrated glucose-6-phosphatase concentrations in platelets intermediate between those in the homozygote and the normal. The miscible urate pool and turnover rate, the rate of incorporation of [14C]glycine into urate, the renal clearance of urate and the percentage excretion of labelled urate by the renal route were within the normal range in both heterozygotes, as were the serum cholesterol and triglyceride concentrations. Thus, a partial deficiency of glucose-6-phosphatase was not associated with the abnormalities of urate or lipoprotein metabolism which are features of homozygous glucose-6-phosphatase deficiency. Erythrocyte phosphoribosyl-pyrophosphate concentration, an increased concentration of which has been postulated as the mechanism responsible for the increased de novo purine biosynthesis in glucose-6-phosphatase deficiency, was found to be within the normal range in erythrocytes from both a homozygote and a heterozygote for this condition."}
{"id": "PMID:183921", "title": "Lipoprotein fractionation by a precipitation method. A simple quantitative procedure.", "content": "A method is described for quantitation of the three major classes of serum lipoproteins. After precipitation of very low density lipoprotein (VLDL) using sodium dodecyl sulphate, the cholesterol and triglyceride content of this lipoprotein class is directly measured. In a second aliquot serum high density lipoprotein (HDL) lipids are measured after precipitation of VLDL and low density lipoprotein (LDL). LDL cholesterol and triglyceride contents are calculated by difference. The procedure requires 2 ml serum, and sensitivity is adequate to permit lipoprotein analyses on umbilical cord serum. Close agreement is observed between this precipitation method and preparative ultracentrifugation.", "contents": "Lipoprotein fractionation by a precipitation method. A simple quantitative procedure. A method is described for quantitation of the three major classes of serum lipoproteins. After precipitation of very low density lipoprotein (VLDL) using sodium dodecyl sulphate, the cholesterol and triglyceride content of this lipoprotein class is directly measured. In a second aliquot serum high density lipoprotein (HDL) lipids are measured after precipitation of VLDL and low density lipoprotein (LDL). LDL cholesterol and triglyceride contents are calculated by difference. The procedure requires 2 ml serum, and sensitivity is adequate to permit lipoprotein analyses on umbilical cord serum. Close agreement is observed between this precipitation method and preparative ultracentrifugation."}
{"id": "PMID:183922", "title": "Nyctohemeral variation and suppressibility of plasma ACTH in various stages of Cushing's disease.", "content": "In order to define nyctohemeral plasma ACTH secretory patterns, frequency plasma ACTH samples were obtained in seven patients with untreated Cushing's disease (i.e. pituitary-dependent Cushing's syndrome), five Cushing's patients treated by bilateral adrenalectomy, four of whom had Nelson's syndrome, and one patient with 21-hydroxylase deficiency (congenital adrenal hyperplasia). A nyctohemeral rhythm of plasma ACTH concentration was apparent in the one patient with the adrenogenital syndrome but not in those with Nelson's syndrome or Cushing's disease. The effect of graded doses of dexamethasone, 2,8 or 32 mg per 24 h period, on plasma ACTH concentrations was studied in patients with untreated or treated Cushing's disease or Nelson's syndrome. In all of these hypercorticotrophic states, the mean plasma ACTH concentraton was not significantly affected by the smallest dose of dexamethasone, was partially suppressed by the intermediate dose, and further suppressed by the largest dose. In contrst, the patient with congenital adrenal hyperplasia and elevated plasma ACTH concentrations showed complete suppression of plasma ACTH levels following the smallest dose of dexamethasone. These findings indicate that there is resistance to ACTH suppression by dexamethasone in all stages of Cushing's disease and suggest that negative feedback of glucocorticoids may be involved in the pathogenesis of this disease.", "contents": "Nyctohemeral variation and suppressibility of plasma ACTH in various stages of Cushing's disease. In order to define nyctohemeral plasma ACTH secretory patterns, frequency plasma ACTH samples were obtained in seven patients with untreated Cushing's disease (i.e. pituitary-dependent Cushing's syndrome), five Cushing's patients treated by bilateral adrenalectomy, four of whom had Nelson's syndrome, and one patient with 21-hydroxylase deficiency (congenital adrenal hyperplasia). A nyctohemeral rhythm of plasma ACTH concentration was apparent in the one patient with the adrenogenital syndrome but not in those with Nelson's syndrome or Cushing's disease. The effect of graded doses of dexamethasone, 2,8 or 32 mg per 24 h period, on plasma ACTH concentrations was studied in patients with untreated or treated Cushing's disease or Nelson's syndrome. In all of these hypercorticotrophic states, the mean plasma ACTH concentraton was not significantly affected by the smallest dose of dexamethasone, was partially suppressed by the intermediate dose, and further suppressed by the largest dose. In contrst, the patient with congenital adrenal hyperplasia and elevated plasma ACTH concentrations showed complete suppression of plasma ACTH levels following the smallest dose of dexamethasone. These findings indicate that there is resistance to ACTH suppression by dexamethasone in all stages of Cushing's disease and suggest that negative feedback of glucocorticoids may be involved in the pathogenesis of this disease."}
{"id": "PMID:183929", "title": "Low-density lipoproteins in patients homozygous for familial hyperbetalipoproteinaemia.", "content": "1. The low-density lipoproteins (LDL; density 1-007-1-063 g/ml) from two patients homozygous for familial hyperbetalipoproteinaemia have been submitted to chemical and physicochemical analysis. 2. The presence of an anomalous lipoprotein with a low proportion of triglyceride and a raised proportion of cholesterol has been confirmed. 3. In one patient, this lipoprotein accounted for about 85% of the LDL, but in the second, the amount varied from about 85% to a point at which it could not be detected among the coexisting normal lipoproteins. 4. The protein moiety of this anomalous LDL has effectively the same amino acid composition as that derived from the LDL of healthy subjects. 5. The proportions of carbohydrate, phospholipid and fatty acids could not be reliably distinguished from those of normal LDL. 6. The molecular weight and diffusion constant of the abnormal lipoprotein, even in the purest preparation, were close to the values determined for normal LDL of similar flotation rate.", "contents": "Low-density lipoproteins in patients homozygous for familial hyperbetalipoproteinaemia. 1. The low-density lipoproteins (LDL; density 1-007-1-063 g/ml) from two patients homozygous for familial hyperbetalipoproteinaemia have been submitted to chemical and physicochemical analysis. 2. The presence of an anomalous lipoprotein with a low proportion of triglyceride and a raised proportion of cholesterol has been confirmed. 3. In one patient, this lipoprotein accounted for about 85% of the LDL, but in the second, the amount varied from about 85% to a point at which it could not be detected among the coexisting normal lipoproteins. 4. The protein moiety of this anomalous LDL has effectively the same amino acid composition as that derived from the LDL of healthy subjects. 5. The proportions of carbohydrate, phospholipid and fatty acids could not be reliably distinguished from those of normal LDL. 6. The molecular weight and diffusion constant of the abnormal lipoprotein, even in the purest preparation, were close to the values determined for normal LDL of similar flotation rate."}
{"id": "PMID:183930", "title": "Intravenous fat-tolerance test in ischaemic heart disease and peripheral vascular disease.", "content": "1. The intravenous fat-tolerance test and serum lipid and lipoprotein measurements were carried out in ninety-three normal subjects, fifty-one patients with ischaemic heart disease and thirty patients with peripheral vascular disease. 2. The fractional turnover rate of exogenous triglyceride was significantly slower in patients with ischaemic heart disease and in patients with peripheral vascular disease than in normal men. The rate was also slower in normal men than normal women. 3. Serum triglyceride and cholesterol concentrations were higher in both vascular disease groups than in control subjects. 4. The proportion of both groups of patients who had a subnormal fractional turnover rate of exogenous triglyceride was 35%, and 32% of patients had hypertriglyceridaemia in the fasting state; 27% of patients were hypercholesterolaemic. 5. Although the intravenous fat-tolerance test did not provide significantly better discrimination between cardiovascular patients and control subjects than did measurement of serum triglyceride, the results suggest that hypertriglyceridaemia in such patients may be separable into a group in which impaired triglyceride clearance may be partly responsible, and a group in which overproduction of serum triglyceride may be the major mechanism of the hyperlipidaemia.", "contents": "Intravenous fat-tolerance test in ischaemic heart disease and peripheral vascular disease. 1. The intravenous fat-tolerance test and serum lipid and lipoprotein measurements were carried out in ninety-three normal subjects, fifty-one patients with ischaemic heart disease and thirty patients with peripheral vascular disease. 2. The fractional turnover rate of exogenous triglyceride was significantly slower in patients with ischaemic heart disease and in patients with peripheral vascular disease than in normal men. The rate was also slower in normal men than normal women. 3. Serum triglyceride and cholesterol concentrations were higher in both vascular disease groups than in control subjects. 4. The proportion of both groups of patients who had a subnormal fractional turnover rate of exogenous triglyceride was 35%, and 32% of patients had hypertriglyceridaemia in the fasting state; 27% of patients were hypercholesterolaemic. 5. Although the intravenous fat-tolerance test did not provide significantly better discrimination between cardiovascular patients and control subjects than did measurement of serum triglyceride, the results suggest that hypertriglyceridaemia in such patients may be separable into a group in which impaired triglyceride clearance may be partly responsible, and a group in which overproduction of serum triglyceride may be the major mechanism of the hyperlipidaemia."}
{"id": "PMID:183927", "title": "Calcium-activated ATPase activity in a plasma membrane-rich preparation of rat pancreas.", "content": "1. Calcium-stimulated ATPase activity was studied in a plasma membrane rich fraction of rat pancreas homogenate. 2. The enzyme is stimulated to the same maximum rate of ATP hydrolysis by either calcium or magnesium, but the apparent requirement for calcium is five-fold lower than for magnesium. 3. Maximum hydrolytic activity of the enzyme is not increased when additional magnesium is added to the optimal amount of calcium. 4. The enzyme does not require Na+ or K+ for its activation by Ca2+ and is not inhibited by ouabain or 2,4-dinitrophenol. 5. Pancreozymin, in concentrations which evoke secretion of zymogen protein, inhibits the calcium-stimulated ATPase. 6. Carbachol and dibutyryl cyclic AMP, in concentrations which increase the release of digestive proteins, do not alter the activity of the calcium-stimulated enzyme. 7. It is suggested that the plasma membrane calcium-activated enzyme, is not involved in the active calcium extrusion, previously reported to occur with use of the various pancreatic secretagogues tested.", "contents": "Calcium-activated ATPase activity in a plasma membrane-rich preparation of rat pancreas. 1. Calcium-stimulated ATPase activity was studied in a plasma membrane rich fraction of rat pancreas homogenate. 2. The enzyme is stimulated to the same maximum rate of ATP hydrolysis by either calcium or magnesium, but the apparent requirement for calcium is five-fold lower than for magnesium. 3. Maximum hydrolytic activity of the enzyme is not increased when additional magnesium is added to the optimal amount of calcium. 4. The enzyme does not require Na+ or K+ for its activation by Ca2+ and is not inhibited by ouabain or 2,4-dinitrophenol. 5. Pancreozymin, in concentrations which evoke secretion of zymogen protein, inhibits the calcium-stimulated ATPase. 6. Carbachol and dibutyryl cyclic AMP, in concentrations which increase the release of digestive proteins, do not alter the activity of the calcium-stimulated enzyme. 7. It is suggested that the plasma membrane calcium-activated enzyme, is not involved in the active calcium extrusion, previously reported to occur with use of the various pancreatic secretagogues tested."}
{"id": "PMID:183926", "title": "Effects of some catecholamines on noradrenergic transmission in the rabbit ear artery.", "content": "1. The effects of noradrenaline, adrenaline, isoprenaline, dopamine and the N-methyl and alpha-methyl homologoues of dopamine were studied on tritium release and on vasoconstrictor responses to sympathetic nerve stimulation in isolated arteries of the rabbit ear after labelling noradrenergic transmitter stores with 3H-noradrenaline. These observations were made in the presence of cocaine (100 muM). 2. Noradrenaline (0-5 and 5 muM) inhibited transmitter release and abolished vasoconstrictor responses. A concentration of 0-05 muM had no effect on transmitter release, although the vasoconstrictor response was reduced and there was sometimes a vasodilator response. 3. Adrenaline in concentrations of 0-05, 0-5 and 5 muM decreased transmitter release and vasoconstrictor responses; sometimes there was a vasodilator response. 4. Isoprenaline in concentrations of 0-05, 0-5 and 5 muM did not affect transmitter release. Vasoconstrictor responses were either unaffected or enhanced by all concentrations of isoprenaline when infusions had been in progress for 15 min; but immediately after beginning the infusion of 5 muM isoprenaline, the response was reduced. 5. Dopamine (0-05, 0-5 and 5 muM) produced a concentration-dependent decrease in transmitter release, but vasoconstrictor responses were not reduced with infusions of 0-05 or 0-5 muM; during infusions of 5 muM, stimulation produced a vasodilator response.", "contents": "Effects of some catecholamines on noradrenergic transmission in the rabbit ear artery. 1. The effects of noradrenaline, adrenaline, isoprenaline, dopamine and the N-methyl and alpha-methyl homologoues of dopamine were studied on tritium release and on vasoconstrictor responses to sympathetic nerve stimulation in isolated arteries of the rabbit ear after labelling noradrenergic transmitter stores with 3H-noradrenaline. These observations were made in the presence of cocaine (100 muM). 2. Noradrenaline (0-5 and 5 muM) inhibited transmitter release and abolished vasoconstrictor responses. A concentration of 0-05 muM had no effect on transmitter release, although the vasoconstrictor response was reduced and there was sometimes a vasodilator response. 3. Adrenaline in concentrations of 0-05, 0-5 and 5 muM decreased transmitter release and vasoconstrictor responses; sometimes there was a vasodilator response. 4. Isoprenaline in concentrations of 0-05, 0-5 and 5 muM did not affect transmitter release. Vasoconstrictor responses were either unaffected or enhanced by all concentrations of isoprenaline when infusions had been in progress for 15 min; but immediately after beginning the infusion of 5 muM isoprenaline, the response was reduced. 5. Dopamine (0-05, 0-5 and 5 muM) produced a concentration-dependent decrease in transmitter release, but vasoconstrictor responses were not reduced with infusions of 0-05 or 0-5 muM; during infusions of 5 muM, stimulation produced a vasodilator response."}
{"id": "PMID:183936", "title": "Intracranial pressure and rapid eye movement sleep in hydrocephalus.", "content": "Intracranial pressure (ICP) was monitored for 24 h in 30 hydrocephalic patients (21 infants, 9 children) representing borderline cases. The need for surgery was uncertain because their hydrocephalus seemed to be more or less arrested. In 13 cases an electroencephalogram, an electro-oculogram, an electromyogram and an actogram were simultaneously recorded. During sleep related to a period of rapid eye movement (REM) fairly regular steep-rising waves of raised ICP recurred every 50-75 min, decreasing slowly to previous levels in 25-40 min. No concomitant clinical symptoms were exhibited. The cerebral pulse wave amplitude increase during REM sleep, but might vary during one period of REM sleep. The relationship between these raised ICP waves and an increase in cerebral blood flow occurring during REM sleep is studied.", "contents": "Intracranial pressure and rapid eye movement sleep in hydrocephalus. Intracranial pressure (ICP) was monitored for 24 h in 30 hydrocephalic patients (21 infants, 9 children) representing borderline cases. The need for surgery was uncertain because their hydrocephalus seemed to be more or less arrested. In 13 cases an electroencephalogram, an electro-oculogram, an electromyogram and an actogram were simultaneously recorded. During sleep related to a period of rapid eye movement (REM) fairly regular steep-rising waves of raised ICP recurred every 50-75 min, decreasing slowly to previous levels in 25-40 min. No concomitant clinical symptoms were exhibited. The cerebral pulse wave amplitude increase during REM sleep, but might vary during one period of REM sleep. The relationship between these raised ICP waves and an increase in cerebral blood flow occurring during REM sleep is studied."}
{"id": "PMID:183937", "title": "[Computer-supported after-care system for patients with tumors using a cancer-register].", "content": "A computerized follow-up system for patients with malignant tumors is described. This system is in use in the \"Chirurgische Klinik der Universitat Munster\" and in the \"Fachklinik Haus Hornheide\". As a special service to these clinics a central cancer registry furnishes periodically lists of patients. These lists are used as surveys of treated cancer patients. It is possible to contact those patients by letter, who do not present themselves for clinical examination. Goals of the system are the documentation of the course of disease, the analysis of survival and the follow-up of the patients. Thus, the clinics manage a comprehensive cancer care program with a minimum lost of contact.", "contents": "[Computer-supported after-care system for patients with tumors using a cancer-register]. A computerized follow-up system for patients with malignant tumors is described. This system is in use in the \"Chirurgische Klinik der Universitat Munster\" and in the \"Fachklinik Haus Hornheide\". As a special service to these clinics a central cancer registry furnishes periodically lists of patients. These lists are used as surveys of treated cancer patients. It is possible to contact those patients by letter, who do not present themselves for clinical examination. Goals of the system are the documentation of the course of disease, the analysis of survival and the follow-up of the patients. Thus, the clinics manage a comprehensive cancer care program with a minimum lost of contact."}
{"id": "PMID:183938", "title": "[Angiodysplasia and the skeletal system].", "content": "1. Congenital angiodysplasias of the extremities are often associated with skeletal disorders, i.e., overgrowth (local giantism, hyperplasia) or reduced growth (hypoplasia). From a clinical point of view three types of combined lesions may be differentiated: (a) a secondary local giantism induced by hemodynamically active congenital a.v. fistulas, usually of intra- and extraosseous location (Weber-type); - (b) local giantism in combination with venous and/or lymphatic angiodysplasias; in this group skeletal overgrowth seems not to be caused by the vascular anomalies but represents more probably a coordinated \"inborn error\" of tissue composition and distribution (Klippel-Trenaunay-type); - (c) hemangiomatosis usually of venous (cavernous) type, affecting soft tissues as well as bones in association with skeletal hypoplasia. There is a retardation of bone growth by substitution and destruction of the epiphysial cartilages by the intraosseous hemangioma (Servelle-Martorelltype). In most cases (a-c) the use of special angiological investigations allows a clear diagnosis particularly concerning the pathogenesis of skeletal disorders. 2. In looking for an unequivocal terminology the clinical classification of these anomalies should be based on the leading clinical symptome, i.e., the giantism or the angiodysplasia. In this respect the vascular findings take on a predominant position. Paying regard to historical aspects the classification may be completed by the additional term \"Klippel-Trenaunay\" type, \"Weber\" type, \"Servelle-Martorell\" type. 3. An exact angiologic diagnosis gives further informations about prognosis and choice of treatment (group I: Early operative elimination or reduction of the a-v shuntvolume; group II and III: \"wait and see!\"; usually conservative treatment with compression bandages).", "contents": "[Angiodysplasia and the skeletal system]. 1. Congenital angiodysplasias of the extremities are often associated with skeletal disorders, i.e., overgrowth (local giantism, hyperplasia) or reduced growth (hypoplasia). From a clinical point of view three types of combined lesions may be differentiated: (a) a secondary local giantism induced by hemodynamically active congenital a.v. fistulas, usually of intra- and extraosseous location (Weber-type); - (b) local giantism in combination with venous and/or lymphatic angiodysplasias; in this group skeletal overgrowth seems not to be caused by the vascular anomalies but represents more probably a coordinated \"inborn error\" of tissue composition and distribution (Klippel-Trenaunay-type); - (c) hemangiomatosis usually of venous (cavernous) type, affecting soft tissues as well as bones in association with skeletal hypoplasia. There is a retardation of bone growth by substitution and destruction of the epiphysial cartilages by the intraosseous hemangioma (Servelle-Martorelltype). In most cases (a-c) the use of special angiological investigations allows a clear diagnosis particularly concerning the pathogenesis of skeletal disorders. 2. In looking for an unequivocal terminology the clinical classification of these anomalies should be based on the leading clinical symptome, i.e., the giantism or the angiodysplasia. In this respect the vascular findings take on a predominant position. Paying regard to historical aspects the classification may be completed by the additional term \"Klippel-Trenaunay\" type, \"Weber\" type, \"Servelle-Martorell\" type. 3. An exact angiologic diagnosis gives further informations about prognosis and choice of treatment (group I: Early operative elimination or reduction of the a-v shuntvolume; group II and III: \"wait and see!\"; usually conservative treatment with compression bandages)."}
{"id": "PMID:183939", "title": "Colorectal adenocarcinoma in patients less than 40 years old.", "content": "Carcinoma of the colorectum knows no age barrier. To date, more than 1,400 cases have been reported to occur in persons less than 40 years old. Our experience with 70 patients treated over a ten-year interval is reviewed. Signs and symptoms in the young are not distinctive. Diagnosis depends on a high index of suspicion and appropriate investigative procedures. Survival times are shorter in the patients who have mucinous and anaplastic tumors, and their incidences seem to be increased in this age segment. Overall survival does not significantly differ from our general experience (41 per cent, 5-year survival). Early diagnosis and prompt institution of aggressive surgical treatment can be expected to produce survival equivalent to that in patients of other ages.", "contents": "Colorectal adenocarcinoma in patients less than 40 years old. Carcinoma of the colorectum knows no age barrier. To date, more than 1,400 cases have been reported to occur in persons less than 40 years old. Our experience with 70 patients treated over a ten-year interval is reviewed. Signs and symptoms in the young are not distinctive. Diagnosis depends on a high index of suspicion and appropriate investigative procedures. Survival times are shorter in the patients who have mucinous and anaplastic tumors, and their incidences seem to be increased in this age segment. Overall survival does not significantly differ from our general experience (41 per cent, 5-year survival). Early diagnosis and prompt institution of aggressive surgical treatment can be expected to produce survival equivalent to that in patients of other ages."}
{"id": "PMID:183943", "title": "[Treatment of essential hypertension with propranolol (author's transl)].", "content": "Effect of long-term administration of propranolol was studied in 90 unselected patients with essential hypertension. At a dose of 180 and 360 mg daily it dropped the blood pressure to at least 155/95 mm Hg in 31 patients (34.4%). Those who responded to propranolol had lower systolic and diastolic blood pre-treatment pressures than those who failed, were younger by an average of eight years, and in no case had decreased plasma-renin activity and demonstrated greater plasma-renin activity after furosemide. After a titration phase with increasing doses of propranolol those who responded were treated in a crossed double-blind test with propranolol or placebo. There was a significant difference in systolic blood pressure (standing and lying) and diastolic pressure (standing) between the two. There was also a highly significant difference in heart rate. During chronic beta blockade the basal and stimulated plasma-renin activity fell. But percentage stimulation of renin secretion was fully maintained. However, aldosterone response was decreased. Serum potassium rose slightly but significantly, cAMP  24-hour urine excretion fell significantly. Electrolyte excretion did not differ between the two treatment periods.", "contents": "[Treatment of essential hypertension with propranolol (author's transl)]. Effect of long-term administration of propranolol was studied in 90 unselected patients with essential hypertension. At a dose of 180 and 360 mg daily it dropped the blood pressure to at least 155/95 mm Hg in 31 patients (34.4%). Those who responded to propranolol had lower systolic and diastolic blood pre-treatment pressures than those who failed, were younger by an average of eight years, and in no case had decreased plasma-renin activity and demonstrated greater plasma-renin activity after furosemide. After a titration phase with increasing doses of propranolol those who responded were treated in a crossed double-blind test with propranolol or placebo. There was a significant difference in systolic blood pressure (standing and lying) and diastolic pressure (standing) between the two. There was also a highly significant difference in heart rate. During chronic beta blockade the basal and stimulated plasma-renin activity fell. But percentage stimulation of renin secretion was fully maintained. However, aldosterone response was decreased. Serum potassium rose slightly but significantly, cAMP  24-hour urine excretion fell significantly. Electrolyte excretion did not differ between the two treatment periods."}
{"id": "PMID:183947", "title": "Induction of lactogenic receptors. I. In the liver of hypophysectomized female rats.", "content": "To identify the hormones which affect lactogenic receptors in the liver of chronically hypophysectomized female rats, hormones were injected s.c. for 7 days. Specific binding (%, SB) of labelled ovine prolactin (PRL) in liver membrane preparations (1000,000 X g pellet) of controls was 1%. Estradiol (E2), cortisone (Con), ACTH or bovine growth hormone (bGH) treatment did not induce hepatic binding sites for PRL. Human GH and a single dose of 2mg PRL (but not lower doses) increased SB of PRL. Treatment with oPRL plus ACTH was less effective than hGH plus ACTH (13 vs 28%); combinations of oPRL plus Con as well as administration of oPRL plus ACTH to hypophysectomized and adrenalectomized female rats did not induce SB for PRL. Therapy with oPRL plus hGH (26%) was more potent than oPRL plus bGH (2%). These studies suggest that PRL, GH, and ACTH induce and in concert with sex steroids, modulate the lactogenic receptors in the female rat liver. The effect of ACTH is not due to increased adrenal corticoid secretion.", "contents": "Induction of lactogenic receptors. I. In the liver of hypophysectomized female rats. To identify the hormones which affect lactogenic receptors in the liver of chronically hypophysectomized female rats, hormones were injected s.c. for 7 days. Specific binding (%, SB) of labelled ovine prolactin (PRL) in liver membrane preparations (1000,000 X g pellet) of controls was 1%. Estradiol (E2), cortisone (Con), ACTH or bovine growth hormone (bGH) treatment did not induce hepatic binding sites for PRL. Human GH and a single dose of 2mg PRL (but not lower doses) increased SB of PRL. Treatment with oPRL plus ACTH was less effective than hGH plus ACTH (13 vs 28%); combinations of oPRL plus Con as well as administration of oPRL plus ACTH to hypophysectomized and adrenalectomized female rats did not induce SB for PRL. Therapy with oPRL plus hGH (26%) was more potent than oPRL plus bGH (2%). These studies suggest that PRL, GH, and ACTH induce and in concert with sex steroids, modulate the lactogenic receptors in the female rat liver. The effect of ACTH is not due to increased adrenal corticoid secretion."}
{"id": "PMID:183948", "title": "Induction of lactogenic receptors. II. Studies on the liver of hypophysectomized male rats and on rats bearing a growth hormone secreting tumor.", "content": "The role of growth hormone (GH), as well as prolactin and ACTH, in the induction of the PRL receptor was investigated both in hypophysectomized male rat livers and in the livers of male rats bearing a GH secreting tumor. After 7 days of s.c. injections, specific binding (% SB) of PRL in controls and rats treated with oPRL, hGH, ACTH, hCG, estradiol (E2), or testosterone (T) was approximately 1%. Treatment with oPRL plus ACTH increased SB to 4%; adding E2 to this combination produced a further increase to 8%, whereas the addition of T decreased hepatic binding to 1%. Combination of hGH with ACTH was most effective, giving a SB of 33%, which is similar to that observed in the liver of rats bearing a GH secreting tumor (36%). These studies suggest that GH acts synergistically with PRL and/or ACTH to increase lactogenic binding sites in the male rat liver and that sex steroids have a modulating effect on this action.", "contents": "Induction of lactogenic receptors. II. Studies on the liver of hypophysectomized male rats and on rats bearing a growth hormone secreting tumor. The role of growth hormone (GH), as well as prolactin and ACTH, in the induction of the PRL receptor was investigated both in hypophysectomized male rat livers and in the livers of male rats bearing a GH secreting tumor. After 7 days of s.c. injections, specific binding (% SB) of PRL in controls and rats treated with oPRL, hGH, ACTH, hCG, estradiol (E2), or testosterone (T) was approximately 1%. Treatment with oPRL plus ACTH increased SB to 4%; adding E2 to this combination produced a further increase to 8%, whereas the addition of T decreased hepatic binding to 1%. Combination of hGH with ACTH was most effective, giving a SB of 33%, which is similar to that observed in the liver of rats bearing a GH secreting tumor (36%). These studies suggest that GH acts synergistically with PRL and/or ACTH to increase lactogenic binding sites in the male rat liver and that sex steroids have a modulating effect on this action."}
{"id": "PMID:183950", "title": "Nuclear poly(A) polymerase from rat liver and a hepatoma. Comparison of properties, molecular weights and amino acid compositions.", "content": "Poly(A) polymerase was extracted from isolated nuclei of rat liver and a rapidly growing solid tumor (Morris hepatoma 3924A). The enzyme from each tissue was purified by successive chromatography on DEAE-Sephadex, phosphoecllulose, hydroxyapatite and QAE-Sephadex. Purified enzyme from both liver and tumor was essentially homogeneous as judged by polyacrylamide gel electrophoresis. Under nondenaturing conditions, enzyme activity corresponded to visible protein and, upon denaturation, a single polypeptide was detected. The enzymes had absolute requirements for Mn2+ as the divalent ion, ATP as the substrate and an oligonucleotide or polynucleotide as the primer. Both enzymes were inhibited by sodium pyrophosphate, N-ethylmaleimide, Rose Bengal, cordycepin 5'-triphosphate and several rifamycin derivatives. The reactions were unaffected by potassium phosphate, alpha-amanitin and pancreatic ribonuclease. However, the liver and hepatoma enzymes differed from each other with respect to apparent Km, primer saturation levels and sensitivity to pH changes. The most striking differences between the enzymes were in their calculated molecular weights (liver, 48000; hepatoma, 60000) and amino acid compositions. Finally, the level of the hepatoma enzyme relative to that of the liver enzyme was at least 1.5-fold higher when expressed per mg DNA.", "contents": "Nuclear poly(A) polymerase from rat liver and a hepatoma. Comparison of properties, molecular weights and amino acid compositions. Poly(A) polymerase was extracted from isolated nuclei of rat liver and a rapidly growing solid tumor (Morris hepatoma 3924A). The enzyme from each tissue was purified by successive chromatography on DEAE-Sephadex, phosphoecllulose, hydroxyapatite and QAE-Sephadex. Purified enzyme from both liver and tumor was essentially homogeneous as judged by polyacrylamide gel electrophoresis. Under nondenaturing conditions, enzyme activity corresponded to visible protein and, upon denaturation, a single polypeptide was detected. The enzymes had absolute requirements for Mn2+ as the divalent ion, ATP as the substrate and an oligonucleotide or polynucleotide as the primer. Both enzymes were inhibited by sodium pyrophosphate, N-ethylmaleimide, Rose Bengal, cordycepin 5'-triphosphate and several rifamycin derivatives. The reactions were unaffected by potassium phosphate, alpha-amanitin and pancreatic ribonuclease. However, the liver and hepatoma enzymes differed from each other with respect to apparent Km, primer saturation levels and sensitivity to pH changes. The most striking differences between the enzymes were in their calculated molecular weights (liver, 48000; hepatoma, 60000) and amino acid compositions. Finally, the level of the hepatoma enzyme relative to that of the liver enzyme was at least 1.5-fold higher when expressed per mg DNA."}
{"id": "PMID:183951", "title": "The inhibition of isocitrate oxidation by palmitoyl-l-carnitine and palmitoyl-C0 A in rat liver mitochondria.", "content": "Palmitoyl-L carnitine decreases the oxidation of isocitrate in rat liver mitochondria in state 3 by 25-30%. Palmitoyl-L-carnitine acts as an additional substrate raising the rate of oxidative phosphorylation, NAD reduction and ATP/ADP ratio in mitochondria. Palmitoyl-CoA added to mitochondria oxidizing isocitrate in state 3 causes a strong inhibition of isocitrate oxidation and of oxidative phosphorylation and a considerable elevation of intramitochondrial NADH/NAD and ATP/ADP ratios. The effect of palmitoyl-CoA is dependent on its concentration and is competitive with ADP. Carnitine restores only oxidative phosphorylation, but the oxidation of isocitrate remains inhibited. Evidence is presented that the transport of isocitrate is not affected by palmitoyl-CoA is due to the inhibition of adenine nucleotide translocation. The kinetic studies of NAD-dependent isocitrate dehydrogenase in the soluble fraction of sonicated mitochondria revealed that the enzyme is very sensitive towards the inhibition by NADH and only very slightly affected by ATP (Ki for NADH and ATP are 0.017 and 3.6 mM respectively). On the basis of the kinetic data the relative contribution of NADH and ATP in the inhibition of isocitrate oxidation by fatty acids was calculated. It is concluded that the inhibition of isocitrate oxidation caused by palmitoyl-L-carnitine and palmitoyl-CoA is primarily due to the increased reduction of NAD, whereas the increase of ATP/ADP ratio is much less important.", "contents": "The inhibition of isocitrate oxidation by palmitoyl-l-carnitine and palmitoyl-C0 A in rat liver mitochondria. Palmitoyl-L carnitine decreases the oxidation of isocitrate in rat liver mitochondria in state 3 by 25-30%. Palmitoyl-L-carnitine acts as an additional substrate raising the rate of oxidative phosphorylation, NAD reduction and ATP/ADP ratio in mitochondria. Palmitoyl-CoA added to mitochondria oxidizing isocitrate in state 3 causes a strong inhibition of isocitrate oxidation and of oxidative phosphorylation and a considerable elevation of intramitochondrial NADH/NAD and ATP/ADP ratios. The effect of palmitoyl-CoA is dependent on its concentration and is competitive with ADP. Carnitine restores only oxidative phosphorylation, but the oxidation of isocitrate remains inhibited. Evidence is presented that the transport of isocitrate is not affected by palmitoyl-CoA is due to the inhibition of adenine nucleotide translocation. The kinetic studies of NAD-dependent isocitrate dehydrogenase in the soluble fraction of sonicated mitochondria revealed that the enzyme is very sensitive towards the inhibition by NADH and only very slightly affected by ATP (Ki for NADH and ATP are 0.017 and 3.6 mM respectively). On the basis of the kinetic data the relative contribution of NADH and ATP in the inhibition of isocitrate oxidation by fatty acids was calculated. It is concluded that the inhibition of isocitrate oxidation caused by palmitoyl-L-carnitine and palmitoyl-CoA is primarily due to the increased reduction of NAD, whereas the increase of ATP/ADP ratio is much less important."}
{"id": "PMID:183952", "title": "Coenzyme properties of NAD+ bound to different matrices through the amino group in the 6-position.", "content": "A method for the synthesis of N6-(2-aminoethyl)-NAD+ is given. The binding of this NAD+ derivative to different soluble and insoluble supports and the direct coupling of NAD+ to epoxyactivated Sepharose are described. Proofs are given that NAD+ is bound through the amino group in 6- position and the NAD+ derivative through the aliphatic amino group of the side chain. Non-enzymic reduction of the bound coenzyme to an almost quantitative extent is possible in all cases, but the enzymic reduction is largely influenced by the support. While N6-(2-aminoethyl)-NAD+ coupled to soluble dextran is nearly completely reducible by different dehydrogenases with a velocity of about 40% of that for free NAD+, the coenzyme bound to different insoluble matrices is very slowly reduced. Only 5% of the coenzyme derivative bound to BrCN-activated Sepharose are reducible, but 40% when it is bound through a spacer. From capacity determinations evidence is given that, even in this coenzyme gel, only those coenzyme molecules are useful in affinity chromatography which are on the surface of the gel grains; it is supposed that this may be due to the slow diffusion of an enzyme into the inner parts of an affinity gel.", "contents": "Coenzyme properties of NAD+ bound to different matrices through the amino group in the 6-position. A method for the synthesis of N6-(2-aminoethyl)-NAD+ is given. The binding of this NAD+ derivative to different soluble and insoluble supports and the direct coupling of NAD+ to epoxyactivated Sepharose are described. Proofs are given that NAD+ is bound through the amino group in 6- position and the NAD+ derivative through the aliphatic amino group of the side chain. Non-enzymic reduction of the bound coenzyme to an almost quantitative extent is possible in all cases, but the enzymic reduction is largely influenced by the support. While N6-(2-aminoethyl)-NAD+ coupled to soluble dextran is nearly completely reducible by different dehydrogenases with a velocity of about 40% of that for free NAD+, the coenzyme bound to different insoluble matrices is very slowly reduced. Only 5% of the coenzyme derivative bound to BrCN-activated Sepharose are reducible, but 40% when it is bound through a spacer. From capacity determinations evidence is given that, even in this coenzyme gel, only those coenzyme molecules are useful in affinity chromatography which are on the surface of the gel grains; it is supposed that this may be due to the slow diffusion of an enzyme into the inner parts of an affinity gel."}
{"id": "PMID:183953", "title": "Evidence for a function of core protein in complex III from beef-heart mitochondria.", "content": "Puried complex III ) ubiquinol-cytochrome c reductase) from beef heart mitochondria was alkylated with iodol [1-14C]acetamide. After 6-8 h of incubation with iodo[1-14C]acetamide, duroquinol and ubiquinol-2-cytochrome c reductase activites were inhibited approximately 50%. During this time 4.5 +/- 1.6 nmol of iodo[1-14C]acetamide reacted per mg of complex III protein. Experiments carried out over 24 h indicated that enzyme activity could be inhibited to 70% and the alkylation of complex III was proportional to inhibition. The rates of cytochrome b and c1 reduction by duroquinol are also decreased upon treatment of complex III with iodoacetamide. Separation of the peptides of complex III by electrophoresis in sodium dodecylsulfate shows that all of the radioactivity is located in a single peptide of 50 000 molecular weight, which has been identified as one of the two core proteins. The possible functions of core protein are discussed.", "contents": "Evidence for a function of core protein in complex III from beef-heart mitochondria. Puried complex III ) ubiquinol-cytochrome c reductase) from beef heart mitochondria was alkylated with iodol [1-14C]acetamide. After 6-8 h of incubation with iodo[1-14C]acetamide, duroquinol and ubiquinol-2-cytochrome c reductase activites were inhibited approximately 50%. During this time 4.5 +/- 1.6 nmol of iodo[1-14C]acetamide reacted per mg of complex III protein. Experiments carried out over 24 h indicated that enzyme activity could be inhibited to 70% and the alkylation of complex III was proportional to inhibition. The rates of cytochrome b and c1 reduction by duroquinol are also decreased upon treatment of complex III with iodoacetamide. Separation of the peptides of complex III by electrophoresis in sodium dodecylsulfate shows that all of the radioactivity is located in a single peptide of 50 000 molecular weight, which has been identified as one of the two core proteins. The possible functions of core protein are discussed."}
{"id": "PMID:183954", "title": "Primary and tertiary structure of the principal human adenylate kinase.", "content": "1. Human adenylate kinase (isoenzyme AK-1-1) from skeletal muscle is a single polypeptide chain of 194 amino-acid residues with an acetylmethionine at the N-terminus and a lysine at the C-terminus. 2. The primary structure of the enzyme was determined: Ac-Met-Glu-Glu-Lys-Leu-Lys-Lys-Thr-Lys-Ile-Ile-Phe-Val-Val-Gly-Gly-Pro-Gly-Ser-Gly-Lys-Gly-Thr-Gln-Cys-Glu-Lys-Ile-Val-Gln-Lys-Tyr-Gly-Tyr-Thr-His-Leu-Ser-Thr-Gly-Asp-Leu-Leu-Arg-Ser-Glu-Val-Ser-Ser-Gly-Ser-Ala-Arg-Gly-Lys-Lys-Leu-Ser-Glu-Ile-Met-Glu-Lys-Gly-Gln-Leu-Val-Pro-Leu-Glu-Thr-Val-Leu-Asp-Met-Leu-Arg-Asp-Ala-Met-Val-Ala-Lys-Val-Asn-Thr-Ser-Lys-Gly-Phe-Leu-Ile-Asp-Gly-Tyr-Pro-Arg-Glu-Val-Gln-Gln-Gly-Glu-Glu-Phe-Glu-Arg-Arg-Ile-Gly-Gln-Pro-Thr-Leu-Leu-Leu-Tyr-Val-Asp-Ala-Gly-Pro-Glu-Thr-Met-Thr-Arg-Arg-Leu-Leu-Lys-Arg-Gly-Glu-Thr-Ser-Gly-Arg-Val-Asp-Asn-Glu-Glu-Thr-Ile-Lys-Lys-Arg-Leu-Glu-Thr-Tyr-Tyr-Lys-Ala-Thr-Glu-Pro-Val-Ile-Ala-Phe-Tyr-Glu-Lys-Arg-Gly-Ile-Val-Arg-Lys-Val-Asn-Ala-Glu-Gly-Ser-Val-Asp-Glu-Val-Phe-Ser-Gln-Val-Cys-Thr-His-Leu-Asp-Ala-Leu-Lys. 3. When the primary structure of the human enzyme was fitted to the electron density map of porcine adenylate kinase, all nine amino acids which are different in the homologous enzymes from pig and man were located on the surface of the molecule. 4. Precession photographs of crystalline human and of crystalline porcine adenylate kinase corroborated the result that the polypeptide chains of the two enzymes are folded in a closely related manner. 5. The structure of human adenylate kinase incorporates the so-called nucleotide-binding domain which is present in a wide variety of proteins in nature. Some implications of this phenomenom for the molecular biology and the molecular pharmacology of man are discussed.", "contents": "Primary and tertiary structure of the principal human adenylate kinase. 1. Human adenylate kinase (isoenzyme AK-1-1) from skeletal muscle is a single polypeptide chain of 194 amino-acid residues with an acetylmethionine at the N-terminus and a lysine at the C-terminus. 2. The primary structure of the enzyme was determined: Ac-Met-Glu-Glu-Lys-Leu-Lys-Lys-Thr-Lys-Ile-Ile-Phe-Val-Val-Gly-Gly-Pro-Gly-Ser-Gly-Lys-Gly-Thr-Gln-Cys-Glu-Lys-Ile-Val-Gln-Lys-Tyr-Gly-Tyr-Thr-His-Leu-Ser-Thr-Gly-Asp-Leu-Leu-Arg-Ser-Glu-Val-Ser-Ser-Gly-Ser-Ala-Arg-Gly-Lys-Lys-Leu-Ser-Glu-Ile-Met-Glu-Lys-Gly-Gln-Leu-Val-Pro-Leu-Glu-Thr-Val-Leu-Asp-Met-Leu-Arg-Asp-Ala-Met-Val-Ala-Lys-Val-Asn-Thr-Ser-Lys-Gly-Phe-Leu-Ile-Asp-Gly-Tyr-Pro-Arg-Glu-Val-Gln-Gln-Gly-Glu-Glu-Phe-Glu-Arg-Arg-Ile-Gly-Gln-Pro-Thr-Leu-Leu-Leu-Tyr-Val-Asp-Ala-Gly-Pro-Glu-Thr-Met-Thr-Arg-Arg-Leu-Leu-Lys-Arg-Gly-Glu-Thr-Ser-Gly-Arg-Val-Asp-Asn-Glu-Glu-Thr-Ile-Lys-Lys-Arg-Leu-Glu-Thr-Tyr-Tyr-Lys-Ala-Thr-Glu-Pro-Val-Ile-Ala-Phe-Tyr-Glu-Lys-Arg-Gly-Ile-Val-Arg-Lys-Val-Asn-Ala-Glu-Gly-Ser-Val-Asp-Glu-Val-Phe-Ser-Gln-Val-Cys-Thr-His-Leu-Asp-Ala-Leu-Lys. 3. When the primary structure of the human enzyme was fitted to the electron density map of porcine adenylate kinase, all nine amino acids which are different in the homologous enzymes from pig and man were located on the surface of the molecule. 4. Precession photographs of crystalline human and of crystalline porcine adenylate kinase corroborated the result that the polypeptide chains of the two enzymes are folded in a closely related manner. 5. The structure of human adenylate kinase incorporates the so-called nucleotide-binding domain which is present in a wide variety of proteins in nature. Some implications of this phenomenom for the molecular biology and the molecular pharmacology of man are discussed."}
{"id": "PMID:183955", "title": "The phosphorylation of rabbit skeletal muscle glycogen synthase by glycogen synthase kinase-2 and adenosine-3':5'-monophosphate-dependent protein kinase.", "content": "Purified glycogen synthase is contaminated with traces of two protein kinases that can phosphorylate the enzyme. One is protein kinase dependent on adenosine 3':5'-monophosphate (cyclic AMP) and the second is an activity termed glycogen synthase kinase-2 [Nimmo, H.G. and Cohen P, (1974)]. Glycogen synthase kinase-2 has been found to be localized relatively specifically in the protein-glycogen complex. It has been purified 4000-fold by two procedures, both of which involve disruption of the complex, followed by the DEAE-cellulose and phosphocellulose chromatographies. However the salt concentration at which glycogen synthase kinase-2 is eluted from DEAE-cellulose depends on the method that is used to disrupt the complex. The results indicate that glycogen synthase kinase-2 is firmly attached to a protein component of the complex. The isolation procedures separate glycogen synthase kinase-2 from phosphorylase kinase, cyclic AMP-dependent protein kinase and other glycogen-metabolising enzymes. Glycogen synthase kinase-2 is the major phosvitin kinase in skeletal muscle, although  glycogen synthase is a six to eight-fold better substrate than phosvitin under the standard assay conditions. Phosphorylase kinase and phosphorylase b are not substrates for glycogen synthase kinase 2. Following incubation with cyclic-AMP-dependent protein kinase, cyclic AMP and Mg-ATP, the phosphorylation of glycogen synthase reaches a plateau at 1.0 molecules of phosphate incorporated per subunit and the activity ratio measured in the absence and presence of glucose 6-phosphate falls from 0.8 to a plateau of 0.18. The Ka for glucose 6-phosphate of this phosphorylated species, termed glycogen synthase b1, is the 0.6 mM. Following incubation with glycogen synthase kinase-2 and Mg-ATP, the phosphorylation reaches a plateau of 0.92 molecules of phosphate incorporated per subunit and the activity ratio decreases to a plateau of 0.08. The Ka for glucose 6-phosphate of this phosphorylated species, termed glycogen synthetase b2, is 4 mM. In the presence of both cyclic-AMP-dependent protein kinase and glycogen synthase kinase-2, the phosphorylation of glycogen synthase reaches a plateau when 1.95 molecules of phoshophate have been incorporated per subunit. The activity ratio is 0.01 and the Ka for glucose 6-phosphate is 10 mM. The results indicate that glycogen synthase can be regulated by two distinct phosphorylation-dephosphorylation cycles. The implication of these findings for the regulation of glycogen synthase in vivo are discussed.", "contents": "The phosphorylation of rabbit skeletal muscle glycogen synthase by glycogen synthase kinase-2 and adenosine-3':5'-monophosphate-dependent protein kinase. Purified glycogen synthase is contaminated with traces of two protein kinases that can phosphorylate the enzyme. One is protein kinase dependent on adenosine 3':5'-monophosphate (cyclic AMP) and the second is an activity termed glycogen synthase kinase-2 [Nimmo, H.G. and Cohen P, (1974)]. Glycogen synthase kinase-2 has been found to be localized relatively specifically in the protein-glycogen complex. It has been purified 4000-fold by two procedures, both of which involve disruption of the complex, followed by the DEAE-cellulose and phosphocellulose chromatographies. However the salt concentration at which glycogen synthase kinase-2 is eluted from DEAE-cellulose depends on the method that is used to disrupt the complex. The results indicate that glycogen synthase kinase-2 is firmly attached to a protein component of the complex. The isolation procedures separate glycogen synthase kinase-2 from phosphorylase kinase, cyclic AMP-dependent protein kinase and other glycogen-metabolising enzymes. Glycogen synthase kinase-2 is the major phosvitin kinase in skeletal muscle, although  glycogen synthase is a six to eight-fold better substrate than phosvitin under the standard assay conditions. Phosphorylase kinase and phosphorylase b are not substrates for glycogen synthase kinase 2. Following incubation with cyclic-AMP-dependent protein kinase, cyclic AMP and Mg-ATP, the phosphorylation of glycogen synthase reaches a plateau at 1.0 molecules of phosphate incorporated per subunit and the activity ratio measured in the absence and presence of glucose 6-phosphate falls from 0.8 to a plateau of 0.18. The Ka for glucose 6-phosphate of this phosphorylated species, termed glycogen synthase b1, is the 0.6 mM. Following incubation with glycogen synthase kinase-2 and Mg-ATP, the phosphorylation reaches a plateau of 0.92 molecules of phosphate incorporated per subunit and the activity ratio decreases to a plateau of 0.08. The Ka for glucose 6-phosphate of this phosphorylated species, termed glycogen synthetase b2, is 4 mM. In the presence of both cyclic-AMP-dependent protein kinase and glycogen synthase kinase-2, the phosphorylation of glycogen synthase reaches a plateau when 1.95 molecules of phoshophate have been incorporated per subunit. The activity ratio is 0.01 and the Ka for glucose 6-phosphate is 10 mM. The results indicate that glycogen synthase can be regulated by two distinct phosphorylation-dephosphorylation cycles. The implication of these findings for the regulation of glycogen synthase in vivo are discussed."}
{"id": "PMID:183956", "title": "Separation of two phosphorylase kinase phosphatases from rabbit skeletal muscle.", "content": "Cyclic-AMP-dependent protein kinase catalyses the activation of phosphorylase kinase and the phosphorylation of two serine residues on the alpha subunit and beta subunit of phosphorylase kinase [Cohen, P., Watson, D.C. and Dixon, G.H. (1975)]. The dephosphorylation of phosphorylase kinase has been shown to be catalysed by two distinct enzymes, termed alpha-phosphorylase kinase phosphatase and beta-phosphorylase kinase phosphatase. These two enzymes show essentially absolute specificity towards the alpha and beta subunits respectively. The two phosphatases copurified through ethanol fractionation, DEAE-cellulose chromatography and ammonium sulphate precipitation, but were separated from each other by a gel filtration on Sephadex G-200. alpha-Phosphorylase kinase phosphatase was purified 500-fold from the ethanol precipitation step, and beta-phosphorylase kinase phosphatase 320-fold. The molecular weights estimated by gel filtration were 170--180 000 for alpha-phosphorylase kinase phosphatase and 75--80 000 for beta-phosphorylase kinase phosphatase. Since the activity of phosphorylase kinase correlates with the state of phosphorylation of the beta subunit (Cohen, P. (1974)), beta-phosphorylase kinase phosphatase is the enzyme which reverses the activation of phosphorylase kinase. alpha-Phosphorylase kinase phosphatase is an enzyme activity that has not been recognised previously. Since the role of the alpha-subunit phosphorylation is to stimulate the rate of dephosphorylation of the beta subunit (Cohen, P. (1974)), alpha-phosphorylase kinase phosphatase can be regarded as the enzyme which inhibits the reversal of the activation of phosphorylase kinase. The implications of these findings for the hormonal control of phosphorylase kinase activity by multisite phosphorylation are discussed.", "contents": "Separation of two phosphorylase kinase phosphatases from rabbit skeletal muscle. Cyclic-AMP-dependent protein kinase catalyses the activation of phosphorylase kinase and the phosphorylation of two serine residues on the alpha subunit and beta subunit of phosphorylase kinase [Cohen, P., Watson, D.C. and Dixon, G.H. (1975)]. The dephosphorylation of phosphorylase kinase has been shown to be catalysed by two distinct enzymes, termed alpha-phosphorylase kinase phosphatase and beta-phosphorylase kinase phosphatase. These two enzymes show essentially absolute specificity towards the alpha and beta subunits respectively. The two phosphatases copurified through ethanol fractionation, DEAE-cellulose chromatography and ammonium sulphate precipitation, but were separated from each other by a gel filtration on Sephadex G-200. alpha-Phosphorylase kinase phosphatase was purified 500-fold from the ethanol precipitation step, and beta-phosphorylase kinase phosphatase 320-fold. The molecular weights estimated by gel filtration were 170--180 000 for alpha-phosphorylase kinase phosphatase and 75--80 000 for beta-phosphorylase kinase phosphatase. Since the activity of phosphorylase kinase correlates with the state of phosphorylation of the beta subunit (Cohen, P. (1974)), beta-phosphorylase kinase phosphatase is the enzyme which reverses the activation of phosphorylase kinase. alpha-Phosphorylase kinase phosphatase is an enzyme activity that has not been recognised previously. Since the role of the alpha-subunit phosphorylation is to stimulate the rate of dephosphorylation of the beta subunit (Cohen, P. (1974)), alpha-phosphorylase kinase phosphatase can be regarded as the enzyme which inhibits the reversal of the activation of phosphorylase kinase. The implications of these findings for the hormonal control of phosphorylase kinase activity by multisite phosphorylation are discussed."}
{"id": "PMID:183957", "title": "Pathophysiology and therapy of hypercalciuria in patients who form recurrent stones.", "content": "There are two alternative mechanisms that might be responsible for idiopathic hypercalciuria in recurrent stone formers: increased intestinal absorption of calcium with parathyroid suppression and overflow hypercalciuria (primary intestinal hyperabsorption) or renal calcium leak with compensatory hyperparathyroidism and intestinal hyperabsorption (primary renal-tubular hypercalciuria). In this study, urinary excretion of cAMP, the intracellular effector substance synthetised under parathyroid hormone stimulation, was found to be in the normal range. This finding would argue against intestinal hyperabsorption of calcium as the primary cause of hypercalciuria.", "contents": "Pathophysiology and therapy of hypercalciuria in patients who form recurrent stones. There are two alternative mechanisms that might be responsible for idiopathic hypercalciuria in recurrent stone formers: increased intestinal absorption of calcium with parathyroid suppression and overflow hypercalciuria (primary intestinal hyperabsorption) or renal calcium leak with compensatory hyperparathyroidism and intestinal hyperabsorption (primary renal-tubular hypercalciuria). In this study, urinary excretion of cAMP, the intracellular effector substance synthetised under parathyroid hormone stimulation, was found to be in the normal range. This finding would argue against intestinal hyperabsorption of calcium as the primary cause of hypercalciuria."}
{"id": "PMID:183960", "title": "Piribedil in Parkinson's syndrome: a clinical study.", "content": "The effect of a new dopamine receptor stimulating agent, piribedil (ET 495), was studied in 10 patients with Parkinson's syndrome, who had had no or a poor response to previous L-DOPA treatment, or had displayed marked side effects during L-DOPA administration. Piribedil produced significant improvement of the functions of activity of daily living (ADL), and appeared to have a preferential effect on parkinsonian tremor. However, treatment was difficult to control primarily because of severe psychiatric side effects.", "contents": "Piribedil in Parkinson's syndrome: a clinical study. The effect of a new dopamine receptor stimulating agent, piribedil (ET 495), was studied in 10 patients with Parkinson's syndrome, who had had no or a poor response to previous L-DOPA treatment, or had displayed marked side effects during L-DOPA administration. Piribedil produced significant improvement of the functions of activity of daily living (ADL), and appeared to have a preferential effect on parkinsonian tremor. However, treatment was difficult to control primarily because of severe psychiatric side effects."}
{"id": "PMID:183961", "title": "Studies on the maturation of thymus stem cells. The effects of catecholamines, histamine and peptide hormones on the expression of T cell alloantigens.", "content": "Studies have been performed in order to investigate the effects of catecholamines. histamine, peptide hormones and various other agents known to increase cellular adenosine 3':5'-cyclic monophosphate (cAMP) levels on the expression of Thy-1 and TL antigens on 14-day fetal thymic stem cells. It has been shown that the proportions of Thy-1 and TL positive cells, as detected by dye exclusion cytotoxicity tests, can be significantly increased by some of these agents and that these effects may be inhibited by beta adrenergic and H2 antagonists. The value of these tests as a means for studying normal thymic stem cell maturation and for investigating T cell deficiency is discussed.", "contents": "Studies on the maturation of thymus stem cells. The effects of catecholamines, histamine and peptide hormones on the expression of T cell alloantigens. Studies have been performed in order to investigate the effects of catecholamines. histamine, peptide hormones and various other agents known to increase cellular adenosine 3':5'-cyclic monophosphate (cAMP) levels on the expression of Thy-1 and TL antigens on 14-day fetal thymic stem cells. It has been shown that the proportions of Thy-1 and TL positive cells, as detected by dye exclusion cytotoxicity tests, can be significantly increased by some of these agents and that these effects may be inhibited by beta adrenergic and H2 antagonists. The value of these tests as a means for studying normal thymic stem cell maturation and for investigating T cell deficiency is discussed."}
{"id": "PMID:183962", "title": "Alterations in the efficacy of naloxone induced by stress, cyclic adenosine monophosphate, and morphine tolerance.", "content": "Pretreatment of mice with a single injection of morphine or by chronic implantation of morphine pellets increased the ability of naloxone to antagonize the analgetic effects of morphine. However, this increased effectiveness of naloxone was also produced by pretreatment with diethylether, ACTH, corticosterone or dexamethasone. Thus, the increased potency of naloxone observed after pretreatment with narcotics may be due, at least in part, to those pretreatments on the pituitary--adrenal axis. In addition, in animals made highly tolerant and dependent by cAMP administration during morphine pellet implantation, the narcotic antagonist potency of naloxone was similar to that of untreated animals.", "contents": "Alterations in the efficacy of naloxone induced by stress, cyclic adenosine monophosphate, and morphine tolerance. Pretreatment of mice with a single injection of morphine or by chronic implantation of morphine pellets increased the ability of naloxone to antagonize the analgetic effects of morphine. However, this increased effectiveness of naloxone was also produced by pretreatment with diethylether, ACTH, corticosterone or dexamethasone. Thus, the increased potency of naloxone observed after pretreatment with narcotics may be due, at least in part, to those pretreatments on the pituitary--adrenal axis. In addition, in animals made highly tolerant and dependent by cAMP administration during morphine pellet implantation, the narcotic antagonist potency of naloxone was similar to that of untreated animals."}
{"id": "PMID:183963", "title": "A comparison of the effects of angiotensin II and heptapeptide on smooth muscle (vascular and uterine).", "content": "On the rabbit isolated aorta, dose-dependent contractions to both angiotensin II and heptapeptide ([des-Asp1]-angiotensin II) were obtained. The curves were parallel, and reached the same maximum level. On the rat isolated uterus, angiotensin II and the heptapeptide displayed non-parallel dose-response curves. Results obtained with angiotensin-analog antagonists and cross-tachyphylaxis experiments suggest that the heptapeptide and angiotensin II act, preferentially, on different populations of receptors in the uterus. The difference in action of indomethacin on recovery from tachyphylaxis to angiotensin II and heptapeptide on rat isolated aorta suggests that the mechanism of induction of tachyphylaxis by these two peptides may differ. SQ 20881, the angiotensin converting enzyme inhibitor, totally inhibited uterine responses to both decapeptide and nonapeptide, while slightly potentiating those to angiotensin II and heptapaptide. Indomethacin had no significant effect on uterine responses to either angiotensin II or the heptapeptide.", "contents": "A comparison of the effects of angiotensin II and heptapeptide on smooth muscle (vascular and uterine). On the rabbit isolated aorta, dose-dependent contractions to both angiotensin II and heptapeptide ([des-Asp1]-angiotensin II) were obtained. The curves were parallel, and reached the same maximum level. On the rat isolated uterus, angiotensin II and the heptapeptide displayed non-parallel dose-response curves. Results obtained with angiotensin-analog antagonists and cross-tachyphylaxis experiments suggest that the heptapeptide and angiotensin II act, preferentially, on different populations of receptors in the uterus. The difference in action of indomethacin on recovery from tachyphylaxis to angiotensin II and heptapeptide on rat isolated aorta suggests that the mechanism of induction of tachyphylaxis by these two peptides may differ. SQ 20881, the angiotensin converting enzyme inhibitor, totally inhibited uterine responses to both decapeptide and nonapeptide, while slightly potentiating those to angiotensin II and heptapaptide. Indomethacin had no significant effect on uterine responses to either angiotensin II or the heptapeptide."}
{"id": "PMID:183964", "title": "Interaction of clonidine with pre- and post-synaptic adrenergic receptors of rat brain: effects on cyclic AMP-generating systems.", "content": "The locus and mechanism of interaction of clonidine with catecholamine-elicited accumulations of cyclic AMP has been investigated in brain slices from control and 6-hydroxydopamine-treated rats of the F-344 and Sprague-Daeley strains. The inhibitory effects of clonidine on the norepinephrine-stimulated accumulation of cyclic AMP and the potentiative effects of clonidine on the isoproterenol-stimulated accumulation of cyclic AMP are present to the same extent in cerebral cortical slices from control and 6-hydroxydopamine-treated Sprague-Dawley rats. Clonidine, at concentrations between 0.0001 and 100 muM has no intrinsic stimulatory activity on cortical cyclic AMP-generating systems from either control or 6-hydroxydopamine-treated rats. In F-344 rats phenoxybenzamine (100 muM) elicits a significant accumulation of cyclic AMP in cerebral cortical slices which can be abolished by pretreatment of rats with 6-hydroxydopamine, or by incubation of tissue slices with either clonidine or sotalol. The hyperresponsiveness to catecholamines usually observed following central administration of 6-hydroxydopamine failed to develop in the F-344 rat. Concentrations of phenoxybenzamine which have no significant stimulatory effects on cyclic AMP accumulation are capable of abolishing the potentiative effects of clonidine on the isoproterenol-stimulated formation of cyclic AMP. The beta-antagonist, sotalol, is a less effective antagonist of isoproterenol-stimulated accumulation of cyclic AMP in the presence of clonidine. Clonidine has no significant effect on the accumulation of cyclic AMP elicited by submaximal concentrations of isoproterenol in cerebellar slices. In toto, the data are consistent with the hypothesis that both the inhibitory effects on norepinephrine-stimulated accumulation of cyclic AMP and the stimulatory effects of clonidine on isoproterenol-elicited accumulation of cyclic AMP are exerted at postsynaptic alpha-adrenoceptors. No evidence was found for a presynaptic generation of cyclic AMP, although clonidine does reverse the stimulatory effects of phenoxybenzamine on cyclic AMP accumulation, presumably by interaction with a presynaptic site controlling norepinephrine release.", "contents": "Interaction of clonidine with pre- and post-synaptic adrenergic receptors of rat brain: effects on cyclic AMP-generating systems. The locus and mechanism of interaction of clonidine with catecholamine-elicited accumulations of cyclic AMP has been investigated in brain slices from control and 6-hydroxydopamine-treated rats of the F-344 and Sprague-Daeley strains. The inhibitory effects of clonidine on the norepinephrine-stimulated accumulation of cyclic AMP and the potentiative effects of clonidine on the isoproterenol-stimulated accumulation of cyclic AMP are present to the same extent in cerebral cortical slices from control and 6-hydroxydopamine-treated Sprague-Dawley rats. Clonidine, at concentrations between 0.0001 and 100 muM has no intrinsic stimulatory activity on cortical cyclic AMP-generating systems from either control or 6-hydroxydopamine-treated rats. In F-344 rats phenoxybenzamine (100 muM) elicits a significant accumulation of cyclic AMP in cerebral cortical slices which can be abolished by pretreatment of rats with 6-hydroxydopamine, or by incubation of tissue slices with either clonidine or sotalol. The hyperresponsiveness to catecholamines usually observed following central administration of 6-hydroxydopamine failed to develop in the F-344 rat. Concentrations of phenoxybenzamine which have no significant stimulatory effects on cyclic AMP accumulation are capable of abolishing the potentiative effects of clonidine on the isoproterenol-stimulated formation of cyclic AMP. The beta-antagonist, sotalol, is a less effective antagonist of isoproterenol-stimulated accumulation of cyclic AMP in the presence of clonidine. Clonidine has no significant effect on the accumulation of cyclic AMP elicited by submaximal concentrations of isoproterenol in cerebellar slices. In toto, the data are consistent with the hypothesis that both the inhibitory effects on norepinephrine-stimulated accumulation of cyclic AMP and the stimulatory effects of clonidine on isoproterenol-elicited accumulation of cyclic AMP are exerted at postsynaptic alpha-adrenoceptors. No evidence was found for a presynaptic generation of cyclic AMP, although clonidine does reverse the stimulatory effects of phenoxybenzamine on cyclic AMP accumulation, presumably by interaction with a presynaptic site controlling norepinephrine release."}
{"id": "PMID:183970", "title": "Effect of cirrhosis on pulmonary fibrogenesis caused by silica dust in rats.", "content": "The cirrhosis in male albino rats was produced after repeated subcutaneous injections of carbon tetrachloride, in dosage schedule as described. A fully developed cirrhosis was observed after 150 days. The silicosis in lungs was produced after single intratracheal injection of silica dust of particle size less than 5 microns and studied up to 180 days. The effect of damaged liver on the development of silicosis in the lungs was studied. It was found that pulmonary fibrosis caused by silica dust appeared to be a tissue reaction confined to the lung tissue alone. The dysfunction of liver did not exert any influence on fibrogenesis in the lungs.", "contents": "Effect of cirrhosis on pulmonary fibrogenesis caused by silica dust in rats. The cirrhosis in male albino rats was produced after repeated subcutaneous injections of carbon tetrachloride, in dosage schedule as described. A fully developed cirrhosis was observed after 150 days. The silicosis in lungs was produced after single intratracheal injection of silica dust of particle size less than 5 microns and studied up to 180 days. The effect of damaged liver on the development of silicosis in the lungs was studied. It was found that pulmonary fibrosis caused by silica dust appeared to be a tissue reaction confined to the lung tissue alone. The dysfunction of liver did not exert any influence on fibrogenesis in the lungs."}
{"id": "PMID:183971", "title": "Effect of quartz dust on the lungs of mice.", "content": "Intratracheal inoculations of quartz dust (250 mg/kg body weight) of a particle size less than 5 mum were given in mice and pulmonary tissue reactions studied over a period of 210 days. Acute inflammatory reaction in the lung parenchyma was observed at early periods and later the aggregates of dust laden macrophages encountered around bronchi and blood vessels. Towards the termination of the experiment at 210 days the fibrotic reaction comprised chiefly of thick compactly arranged reticulin fibers with few collagen fibers which remained restricted to the peribronchial and perivascular areas. There was no silicotic nodule formation in the parenchyma of the lung. The atypical pulmonary tissue response to quartz dust in mice has been attributed to different tissue reactivity.", "contents": "Effect of quartz dust on the lungs of mice. Intratracheal inoculations of quartz dust (250 mg/kg body weight) of a particle size less than 5 mum were given in mice and pulmonary tissue reactions studied over a period of 210 days. Acute inflammatory reaction in the lung parenchyma was observed at early periods and later the aggregates of dust laden macrophages encountered around bronchi and blood vessels. Towards the termination of the experiment at 210 days the fibrotic reaction comprised chiefly of thick compactly arranged reticulin fibers with few collagen fibers which remained restricted to the peribronchial and perivascular areas. There was no silicotic nodule formation in the parenchyma of the lung. The atypical pulmonary tissue response to quartz dust in mice has been attributed to different tissue reactivity."}
{"id": "PMID:183972", "title": "[Effect of Solanum melongena on experimental atheromatosis. VI. Enzyme histochemical, physiopathological and chemical studies on cholesterol-induced atheromatosis in rabbits. Conclusions (author's transl)].", "content": "The mode of action of Solanum Melongena (Sol. Mel.) in its inhibitory effect on the development of atheromatous plaques in cholesterol-induced atheromatosis in rabbits is still unexplained. In this paper the author reports his enzyme histochemical, physiopathological and chemical observations drawing conclusions for future experiments. Animals and experimental conditions were the same as described in the recent studies (see literature no. 2, 15, 16, 17, 18). 1. Enzyme histochemistry: The aortas were removed immediately after death, placed in Holt's solution, freed from the advential fatty tissue, cut into 5-6 mm high cylinders and either processed instantly or preserved in the same fluid at +2 degrees C. From the individual portions cryostat sections (10 mum thick) were cut after the method of Pearse. They were mounted to cover glasses (22 X22) and placed in substrate-filled specially produced cuvettes. The capacity of such a cuvette was 10 ml with room for 4 cover glasses each 4 mm apart. For protection against vaporization small caps of plastic foil were used. The method given by GLOCKNER and SCHMIDT (7) who recently reported their studies in the rat aorta, yielded satisfactory results in small arteries. In thereabbit aorta, however, the results varied markedly, which may be due to greater thickness of the vascular wall. Consequently, despite of all its advantages, this technique could not be employed in this study. The following enzymes were demonstrated: hydrolases: phosphomonoesterase I--3.1.3.1. with naphthol AS-sulphate after BURSTONE in the modification of LOJDA phosphomonoesterase II--3.1.3.2. after BURSTONE as modified by LOJDA with naphthol AS-phosphate and hexazonium pararosanilin leucine aminopeptidase--3.4.1.1. technique according to NACHLAS et al. with leucine beta-naphthylamide lipase--3.1.1.3. after GOMORI (Tween 80) adenosine-5-phosphatase (5'nucleotidase)--3.1.3.5. after GOMORI succinic dehydrogenase--1.3.99.1.--method according to NACHLAS et al. NAD (NADH and NADP (NADPH) diaphorase--1.4.1.2.--1.4.1.4., technique of SCARPELLI, HESS and PEARSE as modified by LOJDA (see article) Substratefree or heatinactivated controls were prepared for each histochemical demonstration. Several additional series with phenazine methosulphate (PMS) as an intermediate electron acceptor or such without PMS as well as preparations with KCN or without KCN were examined for the demonstration of anaerobic dehydrogenases. However, to avoid the nothing dehydrogenase effect only PMS-processed specimens were evaluated. For histological information several additional sections of the tissue samples were stained with haematoxylin-eosin or with elastica-van Gieson and Weigert's iron haematoxylin in combination. The enzyme histochemical preparations were embedded in Kaiser's glycerine gelatin, the histological sections were embedded in Caedox. The test animals were grouped like in the recent experiments (see literature no. 2, 15, 16, 17, 18). 2...", "contents": "[Effect of Solanum melongena on experimental atheromatosis. VI. Enzyme histochemical, physiopathological and chemical studies on cholesterol-induced atheromatosis in rabbits. Conclusions (author's transl)]. The mode of action of Solanum Melongena (Sol. Mel.) in its inhibitory effect on the development of atheromatous plaques in cholesterol-induced atheromatosis in rabbits is still unexplained. In this paper the author reports his enzyme histochemical, physiopathological and chemical observations drawing conclusions for future experiments. Animals and experimental conditions were the same as described in the recent studies (see literature no. 2, 15, 16, 17, 18). 1. Enzyme histochemistry: The aortas were removed immediately after death, placed in Holt's solution, freed from the advential fatty tissue, cut into 5-6 mm high cylinders and either processed instantly or preserved in the same fluid at +2 degrees C. From the individual portions cryostat sections (10 mum thick) were cut after the method of Pearse. They were mounted to cover glasses (22 X22) and placed in substrate-filled specially produced cuvettes. The capacity of such a cuvette was 10 ml with room for 4 cover glasses each 4 mm apart. For protection against vaporization small caps of plastic foil were used. The method given by GLOCKNER and SCHMIDT (7) who recently reported their studies in the rat aorta, yielded satisfactory results in small arteries. In thereabbit aorta, however, the results varied markedly, which may be due to greater thickness of the vascular wall. Consequently, despite of all its advantages, this technique could not be employed in this study. The following enzymes were demonstrated: hydrolases: phosphomonoesterase I--3.1.3.1. with naphthol AS-sulphate after BURSTONE in the modification of LOJDA phosphomonoesterase II--3.1.3.2. after BURSTONE as modified by LOJDA with naphthol AS-phosphate and hexazonium pararosanilin leucine aminopeptidase--3.4.1.1. technique according to NACHLAS et al. with leucine beta-naphthylamide lipase--3.1.1.3. after GOMORI (Tween 80) adenosine-5-phosphatase (5'nucleotidase)--3.1.3.5. after GOMORI succinic dehydrogenase--1.3.99.1.--method according to NACHLAS et al. NAD (NADH and NADP (NADPH) diaphorase--1.4.1.2.--1.4.1.4., technique of SCARPELLI, HESS and PEARSE as modified by LOJDA (see article) Substratefree or heatinactivated controls were prepared for each histochemical demonstration. Several additional series with phenazine methosulphate (PMS) as an intermediate electron acceptor or such without PMS as well as preparations with KCN or without KCN were examined for the demonstration of anaerobic dehydrogenases. However, to avoid the nothing dehydrogenase effect only PMS-processed specimens were evaluated. For histological information several additional sections of the tissue samples were stained with haematoxylin-eosin or with elastica-van Gieson and Weigert's iron haematoxylin in combination. The enzyme histochemical preparations were embedded in Kaiser's glycerine gelatin, the histological sections were embedded in Caedox. The test animals were grouped like in the recent experiments (see literature no. 2, 15, 16, 17, 18). 2..."}
{"id": "PMID:183973", "title": "Comparative karyometric studies on small pseudolobuli and hepatomas in thioacetamide induced liver cirrhosis.", "content": "In the tumorous phase of TAA-induced cirrhosis of the liver comparative studies on the mitotic index, on the frequency of binucleated liver cells and on nuclear volume showed approximately similar values in the small pseudolobuli and in several hepatomas. Obviously \"minimum deviation hepatomas\" had developed. Decrease of ploidy characteristic for hepatomas was observed. In thioacetamide hepatomas the phenomenon of quadrupling of the cell nuclei due to dysfunctional nuclear edema occurred whereas the normal nuclei of liver cells can only double in volume in all phases of thioacetamide-intoxication. Particular karyometric aspects of the nuclear-nucleolar metabolism of hepatoma cells following thioacetamide intoxication are discussed.", "contents": "Comparative karyometric studies on small pseudolobuli and hepatomas in thioacetamide induced liver cirrhosis. In the tumorous phase of TAA-induced cirrhosis of the liver comparative studies on the mitotic index, on the frequency of binucleated liver cells and on nuclear volume showed approximately similar values in the small pseudolobuli and in several hepatomas. Obviously \"minimum deviation hepatomas\" had developed. Decrease of ploidy characteristic for hepatomas was observed. In thioacetamide hepatomas the phenomenon of quadrupling of the cell nuclei due to dysfunctional nuclear edema occurred whereas the normal nuclei of liver cells can only double in volume in all phases of thioacetamide-intoxication. Particular karyometric aspects of the nuclear-nucleolar metabolism of hepatoma cells following thioacetamide intoxication are discussed."}
{"id": "PMID:183974", "title": "Interaction of Lens culinaris lectin, concanavalin A, Ricinus communis agglutinin and wheat germ agglutinin with the cell surface of normal and transformed rat liver cells.", "content": "The observation of BOREK et al. (1973) on nonagglutinability of transformed rat liver cells by Lens culinaris lectin and our ultrastructural findings of a greater mobility of the Lens culinaris lectin receptors on transformed rat liver cells as compared to normal rat liver cells (ROTH 1975) initiated the present agglutination experiments on liver cells with lectins. For agglutination assay the microhemadsorption technique after FURMANSKI et al. (1973) was used with exception of several tests on EDTA-detached cells. The transformed rat liver cells exhibited, in contrast to the findings of BOREK et al. (1973), a positive microhemadsorption with Lens culinaris lectin as well as with Concanavalin A, Ricinus communis lectin and wheat germ agglutinin whereas the normal rat liver cells became positive only after a brief trypsin treatment. The significance of the difference in agglutinability of rat liver cells with Lens culinaris lectin and the other lectins used is discussed with regard to the cell-cell interaction mediated by lectins.", "contents": "Interaction of Lens culinaris lectin, concanavalin A, Ricinus communis agglutinin and wheat germ agglutinin with the cell surface of normal and transformed rat liver cells. The observation of BOREK et al. (1973) on nonagglutinability of transformed rat liver cells by Lens culinaris lectin and our ultrastructural findings of a greater mobility of the Lens culinaris lectin receptors on transformed rat liver cells as compared to normal rat liver cells (ROTH 1975) initiated the present agglutination experiments on liver cells with lectins. For agglutination assay the microhemadsorption technique after FURMANSKI et al. (1973) was used with exception of several tests on EDTA-detached cells. The transformed rat liver cells exhibited, in contrast to the findings of BOREK et al. (1973), a positive microhemadsorption with Lens culinaris lectin as well as with Concanavalin A, Ricinus communis lectin and wheat germ agglutinin whereas the normal rat liver cells became positive only after a brief trypsin treatment. The significance of the difference in agglutinability of rat liver cells with Lens culinaris lectin and the other lectins used is discussed with regard to the cell-cell interaction mediated by lectins."}
{"id": "PMID:183975", "title": "Structural patterns and histological behaviour of experimental sarcomas. I. General considerations, histology and histochemistry.", "content": "Methylcholanthrene-induced rat sarcomas were used as a model for the examination of morphological and cytological differentiations in tumours of the connective tissue. Particular attention was paid to the question how far these sarcomas are comparable to human connective tissue tumours. The histological examination yields a broad spectrum of mesenchymal differentiations ranging from undifferentiated anaplastic sarcomas over less differentiated fibrosarcomas and malignant  fibrous histocytomas to well-differentiated fibrosarcomas, myosarcomas and haemangiopericytomas. It is worth mentioning that different histological structures can be encountered with one and the same tumour.", "contents": "Structural patterns and histological behaviour of experimental sarcomas. I. General considerations, histology and histochemistry. Methylcholanthrene-induced rat sarcomas were used as a model for the examination of morphological and cytological differentiations in tumours of the connective tissue. Particular attention was paid to the question how far these sarcomas are comparable to human connective tissue tumours. The histological examination yields a broad spectrum of mesenchymal differentiations ranging from undifferentiated anaplastic sarcomas over less differentiated fibrosarcomas and malignant  fibrous histocytomas to well-differentiated fibrosarcomas, myosarcomas and haemangiopericytomas. It is worth mentioning that different histological structures can be encountered with one and the same tumour."}
{"id": "PMID:183976", "title": "Oxygenation of a dipyrromethene model for bilirubin: formation of a singlet oxygen-like product.", "content": "An oxodipyrromethene model compound for bilirubin is found to undergo oxidation to a blue tetrapyrrole and a water-propentdyopent on a silica gel thin layer chromatography plate. The reaction involves ground state oxygen and requires silica gel, although the propentdyopent is an expected product from reaction with singlet oxygen.", "contents": "Oxygenation of a dipyrromethene model for bilirubin: formation of a singlet oxygen-like product. An oxodipyrromethene model compound for bilirubin is found to undergo oxidation to a blue tetrapyrrole and a water-propentdyopent on a silica gel thin layer chromatography plate. The reaction involves ground state oxygen and requires silica gel, although the propentdyopent is an expected product from reaction with singlet oxygen."}
{"id": "PMID:183977", "title": "Some properties of external NADH oxidation by human placental mitochondria.", "content": "Isolated human term placenta mitochondria catalyse oxidation of external NADH in the presence of cytochrome c. This reaction is insensitive to the respiratory chain inhibitors such as rotenone and antimycin A, and is not coupled to phosphorylation. Comparison of the effect of Mg++ ion on NADH plus cytochrome c oxidation by human term placental, human skeletal muscle and rat skeletal mitochondria showed that Mg++ ion exerts an inhibitory effect in the case of human mitochondria and a stimulatory effect in the case of rat skeletal muscle mitochondria.", "contents": "Some properties of external NADH oxidation by human placental mitochondria. Isolated human term placenta mitochondria catalyse oxidation of external NADH in the presence of cytochrome c. This reaction is insensitive to the respiratory chain inhibitors such as rotenone and antimycin A, and is not coupled to phosphorylation. Comparison of the effect of Mg++ ion on NADH plus cytochrome c oxidation by human term placental, human skeletal muscle and rat skeletal mitochondria showed that Mg++ ion exerts an inhibitory effect in the case of human mitochondria and a stimulatory effect in the case of rat skeletal muscle mitochondria."}
{"id": "PMID:183979", "title": "Metabolic requirements for entry of DNA in Branhamella catarrhalis.", "content": "Although requirements for transformation in Branhamella catarrhalis are quite complex, DNA synthesis does not appear to be one of these needs, as indicated by the inability of nalidixic acid to interefere with transformation. Exogenous sources of energy, such as cAMP and cGMP also failed to enhance frequency, suggesting cells may actively engage in energy production to achieve uptake of DNA, or lack a transport mechanism for these compounds.", "contents": "Metabolic requirements for entry of DNA in Branhamella catarrhalis. Although requirements for transformation in Branhamella catarrhalis are quite complex, DNA synthesis does not appear to be one of these needs, as indicated by the inability of nalidixic acid to interefere with transformation. Exogenous sources of energy, such as cAMP and cGMP also failed to enhance frequency, suggesting cells may actively engage in energy production to achieve uptake of DNA, or lack a transport mechanism for these compounds."}
{"id": "PMID:183980", "title": "3-Hydroxy-3-methylglutaric acid and triton-induced hyperlipidemia in rats.", "content": "3-Hydroxy-3-methylglutaric acid (HMG) significantly decreased cholesterol, triglyceride and phospholipid levels in whole serum, serum beta-lipoproteins and liver of Triton-induced hyperlipidemic rats. Therapeutically 50 mg HMG/kg is equivalent to 200 mg nicotinic acid/kg in lowering all these lipid parameters. HMG may exert its hypolipidemic effect through inhibition of lipoprotein synthesis.", "contents": "3-Hydroxy-3-methylglutaric acid and triton-induced hyperlipidemia in rats. 3-Hydroxy-3-methylglutaric acid (HMG) significantly decreased cholesterol, triglyceride and phospholipid levels in whole serum, serum beta-lipoproteins and liver of Triton-induced hyperlipidemic rats. Therapeutically 50 mg HMG/kg is equivalent to 200 mg nicotinic acid/kg in lowering all these lipid parameters. HMG may exert its hypolipidemic effect through inhibition of lipoprotein synthesis."}
{"id": "PMID:183989", "title": "Correlation between leuteinizing hormone responses to luteinizing hormone-releasing hormone (LH-RH) and to D-leu-6-LH-RH-ethylamide in patients with hypothalamo-pituitary disease.", "content": "Seventeen patients (eleven females and six males) with organic hypothalamo-pituitary disease were subjected to a test consisting of a rapid intravenous injection of 50 mug of luteinizing hormone-releasing hormone (LH-RH) at 8:00 A.M., with blood sampling before and 30 and 60 minutes afterward. Two to four weeks later, a rapid intravenous injection of 50 mug of D-Leu-6-des-Gly-10-LH-RH-ethylamide (D-Leu-6-LH-RH-EA) was given under similar conditions, with blood sampling before and 30, 60, and 90 minutes afterward. Serum LH levels were determined by radioimmunoassay. D-Leu-6-LH-RH-EA caused a greater and more sustained rise in serum LH levels than did an equal dose of LH-RH. However, functional classifications of patients were similar with either preparation. This finding suggests that acute administration of D-Leu-6-LH-RH-EA does not cause a higher number of relevant responses as compared with LH-RH, but only a greater stimulation of LH releases in responsive patients.", "contents": "Correlation between leuteinizing hormone responses to luteinizing hormone-releasing hormone (LH-RH) and to D-leu-6-LH-RH-ethylamide in patients with hypothalamo-pituitary disease. Seventeen patients (eleven females and six males) with organic hypothalamo-pituitary disease were subjected to a test consisting of a rapid intravenous injection of 50 mug of luteinizing hormone-releasing hormone (LH-RH) at 8:00 A.M., with blood sampling before and 30 and 60 minutes afterward. Two to four weeks later, a rapid intravenous injection of 50 mug of D-Leu-6-des-Gly-10-LH-RH-ethylamide (D-Leu-6-LH-RH-EA) was given under similar conditions, with blood sampling before and 30, 60, and 90 minutes afterward. Serum LH levels were determined by radioimmunoassay. D-Leu-6-LH-RH-EA caused a greater and more sustained rise in serum LH levels than did an equal dose of LH-RH. However, functional classifications of patients were similar with either preparation. This finding suggests that acute administration of D-Leu-6-LH-RH-EA does not cause a higher number of relevant responses as compared with LH-RH, but only a greater stimulation of LH releases in responsive patients."}
{"id": "PMID:183990", "title": "[Interaction of norethindrone on estrogen and progesterone receptors in the rabbit uterine cytosol (author's transl)].", "content": "Norethindrone (ENT), which is a representative in estrane series of progestogen, is not only strongly progestational but also estrogenic and in some cases, antiestrogenic. To understand progestational effect and antiestrogenic effect, the interactions of ENT on estrogen and progestogen receptors were studied in the uterine cytosol of white female rabbit. The 274,200 X G supernatant of uterine homogenate was used as cytosol. 3H-Estradiol, 3H-Progesterone, 3H-ENT or cold ENT were incubated with uterine cytosol at 4 degrees C for 2 hours. Results are as follows: 1. Sucrose gradient centrifugation [5 approximately 20% linear and 40,000 rpm (159,200 X G) for 16 hours at 4 degrees C]: ENT was bound to extrogen 8S receptor in immature rabbit uterus (Fig. 2 & 3), and to progestogen 8S receptor in estrogen primed rabbit uterus (Fig. 5). 2. Kinetic study, determined by dextran coated charcoal (0.001% dextran and 0.1% charcoal): (1) In the uterine cytosol of immature rabbit, 3H-estradiol-receptor binding was observed with Kd divide by 3.6 X 10-9 M and it was revealed that ENT was a competitive inhibitor to this binding with Ki divide by 2.6 X 10-6 M, as in Fig. 6. (2) 8S component, obtained by centrifugation of uterine cytosol (Fig. 1) in estrogen primed rabbit, binds 3H-progesterone with Kd divide by 8.1 X 10-10 M and Bm (maximal binding sites) divide by 5.0 X 10-8 M/mg of protein, and ENT was a competitive inhibitor in this binding with Ki divide by 2.3 X 10-9 M (FIG. 7 & 8). 3H-ENT-8S binding was demonstrated with Kd divide by 1.1 X 10-9 M and Bm divide by 8.7 X 10-8 M/mg of cytosol protein (Fig. 8). These results indicate: (a) ENT is bound to both estrogen and progestogen receptors in 8S macromolecules of uterine cytosol, (b) competitive inhibition of ENT to these bindings indicated that ENT is bound to these receptors at the steroid binding sites where estradiol and progesterone bind to, (c) ENT has much more affinity to progestogen receptor (Ki divide by 2.3 X 10-9 M) than to estrogen receptor (Ki divide 2.6 X 10-6 M), (d) while ENT is bound to progestogen and estrogen receptors at the same time, Bm of ENT (8.7 X 10-8 M/mg of cytosol protein) is more than Bm of progesterone (5.0 X 10-9 M/mg of cytosol protein), and Kd of ENT (1.1 X 10-9 M) was less than Ki of ENT (2.3 X 10-9 M) in the binding to progesterone-receptor. Biologically, while ENT is bound to progestogen -receptor with high affinity and to estrogen receptor with low affinity, ENT is actually progestational in low dose and antiestrogenic in high dose but the anti-estrogenicity seems to be incomplete in vivo as ENT may be metabolized to a potent estrogenic compound, ethinyl estradiol", "contents": "[Interaction of norethindrone on estrogen and progesterone receptors in the rabbit uterine cytosol (author's transl)]. Norethindrone (ENT), which is a representative in estrane series of progestogen, is not only strongly progestational but also estrogenic and in some cases, antiestrogenic. To understand progestational effect and antiestrogenic effect, the interactions of ENT on estrogen and progestogen receptors were studied in the uterine cytosol of white female rabbit. The 274,200 X G supernatant of uterine homogenate was used as cytosol. 3H-Estradiol, 3H-Progesterone, 3H-ENT or cold ENT were incubated with uterine cytosol at 4 degrees C for 2 hours. Results are as follows: 1. Sucrose gradient centrifugation [5 approximately 20% linear and 40,000 rpm (159,200 X G) for 16 hours at 4 degrees C]: ENT was bound to extrogen 8S receptor in immature rabbit uterus (Fig. 2 & 3), and to progestogen 8S receptor in estrogen primed rabbit uterus (Fig. 5). 2. Kinetic study, determined by dextran coated charcoal (0.001% dextran and 0.1% charcoal): (1) In the uterine cytosol of immature rabbit, 3H-estradiol-receptor binding was observed with Kd divide by 3.6 X 10-9 M and it was revealed that ENT was a competitive inhibitor to this binding with Ki divide by 2.6 X 10-6 M, as in Fig. 6. (2) 8S component, obtained by centrifugation of uterine cytosol (Fig. 1) in estrogen primed rabbit, binds 3H-progesterone with Kd divide by 8.1 X 10-10 M and Bm (maximal binding sites) divide by 5.0 X 10-8 M/mg of protein, and ENT was a competitive inhibitor in this binding with Ki divide by 2.3 X 10-9 M (FIG. 7 & 8). 3H-ENT-8S binding was demonstrated with Kd divide by 1.1 X 10-9 M and Bm divide by 8.7 X 10-8 M/mg of cytosol protein (Fig. 8). These results indicate: (a) ENT is bound to both estrogen and progestogen receptors in 8S macromolecules of uterine cytosol, (b) competitive inhibition of ENT to these bindings indicated that ENT is bound to these receptors at the steroid binding sites where estradiol and progesterone bind to, (c) ENT has much more affinity to progestogen receptor (Ki divide by 2.3 X 10-9 M) than to estrogen receptor (Ki divide 2.6 X 10-6 M), (d) while ENT is bound to progestogen and estrogen receptors at the same time, Bm of ENT (8.7 X 10-8 M/mg of cytosol protein) is more than Bm of progesterone (5.0 X 10-9 M/mg of cytosol protein), and Kd of ENT (1.1 X 10-9 M) was less than Ki of ENT (2.3 X 10-9 M) in the binding to progesterone-receptor. Biologically, while ENT is bound to progestogen -receptor with high affinity and to estrogen receptor with low affinity, ENT is actually progestational in low dose and antiestrogenic in high dose but the anti-estrogenicity seems to be incomplete in vivo as ENT may be metabolized to a potent estrogenic compound, ethinyl estradiol"}
{"id": "PMID:183991", "title": "[Studies on progesterone receptor in rabbit uterine cytosol -- nuclear translocation and chromatin binding-- (author's transl)].", "content": "Estrogen priming increases uterine 8S macromolecule which binds progesterone specifically. Progesterone-8S complex in the cytoplasm enters into nucleus and is bound to chromatin finally. In this paper, the mode of nuclear translocation of steroid in exchange assay of receptor introduced by Anderson et al., and the mode of binding to chromatin were studied on the progesterone-receptor complex in the uterus of estrogen primed female rabbit. 1. After intravenous administration of 200 mug progesterone into the estrogen primed immature rabbit, uterine nuclei were prepared by the method in Table 1. These nuclei were incubated with 3H-progesterone and cold steroids at 4 degrees C for 30 minutes, and then washed with buffer A. The radioactivity of the nuclei was counted. This experiment was performed at 4 degrees C because progesterone receptor and chromatin were observed to be degraded at 37 degrees C for 20 minutes. The effect of cold steroids in vitro on the incorporation of 3H-progesterone into the uterine nuclei of rabbit pretreated with progesterone was found to be similar to their effect on progesterone-receptor binding in cytosol or chromatin (Fig. 1). 2. The effect of cold steroids on 3H-progesterone-receptor-chromatin triplex (Table 2 and Fig. 2) was examined. Once 3H-progesterone-receptor-chromatin triplex was formed, it was difficult to exchange 3H-progesterone to other steroids at 4 degrees C. These results (1 & 2) indicate that progesterone-receptor complex enters into nucleus and is bound to chromatin. Exchange of steroid may occur in the nuclear progesterone-receptor complex, which is free from the binding with chromatin. And thus exchange assay cannot represent quantitative data on receptor content. 3. 3H-progesterone-8S or 5S complexes were obtained by 5 approximately 20% sucrose linear gradient centrifugation (Fig. 3). The same molar concentration of these complexes from estrogen primed or castrated rabbit uterus were incubated with primed uterine chromatin for 30 minutes. Then the chromatin was washed with buffer A and the radioactivity was counted. It was shown in Fig. 4 that 3H-progesterone-8S complex was bound to chromatin much more tightly than 3H-progesterone 5-S complex in preparations obtained from both castrated or primed uterine cytosols. All these results indicate that 8S may be the biologically active form of the receptor. 4.3H-progesterone uptake into uterine nuclei was observed in very limited amount following the injection into uterine artery. The radioactivity in nuclei decreased easily by washing with buffer A as in Fig. 5. The small amount of residual radioactivity after washing, that is, very limited number of binding sites with high affinity is considered to be indicative of biologically active binding.", "contents": "[Studies on progesterone receptor in rabbit uterine cytosol -- nuclear translocation and chromatin binding-- (author's transl)]. Estrogen priming increases uterine 8S macromolecule which binds progesterone specifically. Progesterone-8S complex in the cytoplasm enters into nucleus and is bound to chromatin finally. In this paper, the mode of nuclear translocation of steroid in exchange assay of receptor introduced by Anderson et al., and the mode of binding to chromatin were studied on the progesterone-receptor complex in the uterus of estrogen primed female rabbit. 1. After intravenous administration of 200 mug progesterone into the estrogen primed immature rabbit, uterine nuclei were prepared by the method in Table 1. These nuclei were incubated with 3H-progesterone and cold steroids at 4 degrees C for 30 minutes, and then washed with buffer A. The radioactivity of the nuclei was counted. This experiment was performed at 4 degrees C because progesterone receptor and chromatin were observed to be degraded at 37 degrees C for 20 minutes. The effect of cold steroids in vitro on the incorporation of 3H-progesterone into the uterine nuclei of rabbit pretreated with progesterone was found to be similar to their effect on progesterone-receptor binding in cytosol or chromatin (Fig. 1). 2. The effect of cold steroids on 3H-progesterone-receptor-chromatin triplex (Table 2 and Fig. 2) was examined. Once 3H-progesterone-receptor-chromatin triplex was formed, it was difficult to exchange 3H-progesterone to other steroids at 4 degrees C. These results (1 & 2) indicate that progesterone-receptor complex enters into nucleus and is bound to chromatin. Exchange of steroid may occur in the nuclear progesterone-receptor complex, which is free from the binding with chromatin. And thus exchange assay cannot represent quantitative data on receptor content. 3. 3H-progesterone-8S or 5S complexes were obtained by 5 approximately 20% sucrose linear gradient centrifugation (Fig. 3). The same molar concentration of these complexes from estrogen primed or castrated rabbit uterus were incubated with primed uterine chromatin for 30 minutes. Then the chromatin was washed with buffer A and the radioactivity was counted. It was shown in Fig. 4 that 3H-progesterone-8S complex was bound to chromatin much more tightly than 3H-progesterone 5-S complex in preparations obtained from both castrated or primed uterine cytosols. All these results indicate that 8S may be the biologically active form of the receptor. 4.3H-progesterone uptake into uterine nuclei was observed in very limited amount following the injection into uterine artery. The radioactivity in nuclei decreased easily by washing with buffer A as in Fig. 5. The small amount of residual radioactivity after washing, that is, very limited number of binding sites with high affinity is considered to be indicative of biologically active binding."}
{"id": "PMID:183996", "title": "Studies on glucagon secretion using isolated islets of Langerhans of the rat.", "content": "Glucagon secretion and its control have been studied in perifused isolated islets of Langerhans of the rat. It was shown that a low concentration of glucose per se does not cause increased glucagon secretion, but that at low glucose concentrations the amino acid arginine stimulates a biphasic secretory response. Such amino acid stimulated glucagon secretion can be suppressed by increasing the glucose content of the perifused media from 1.67 to 5.5 or 16.7 mM; insulin secretion is also then increased. Since high concentrations of added porcine insulin (10 mU/ml) did not affect amino acid stimulated glucagon secretion at low glucose concentration, it was concluded that high concentrations of glucose and not insulin secreted in response to that glucose are probably responsible for suppression of glucagon secretion. At low concentrations of glucose, epinephrine (2.5 X 10(-7) M) also stimulated glucagon secretion. It is concluded that isolated rat islets of Langerhans can be used for the study of glucagon secretion in vitro, and that substances appearing in the blood in vivo at low glucose concentrations are probably responsible for increased glucagon secretion under conditions associated with hypoglycemia.", "contents": "Studies on glucagon secretion using isolated islets of Langerhans of the rat. Glucagon secretion and its control have been studied in perifused isolated islets of Langerhans of the rat. It was shown that a low concentration of glucose per se does not cause increased glucagon secretion, but that at low glucose concentrations the amino acid arginine stimulates a biphasic secretory response. Such amino acid stimulated glucagon secretion can be suppressed by increasing the glucose content of the perifused media from 1.67 to 5.5 or 16.7 mM; insulin secretion is also then increased. Since high concentrations of added porcine insulin (10 mU/ml) did not affect amino acid stimulated glucagon secretion at low glucose concentration, it was concluded that high concentrations of glucose and not insulin secreted in response to that glucose are probably responsible for suppression of glucagon secretion. At low concentrations of glucose, epinephrine (2.5 X 10(-7) M) also stimulated glucagon secretion. It is concluded that isolated rat islets of Langerhans can be used for the study of glucagon secretion in vitro, and that substances appearing in the blood in vivo at low glucose concentrations are probably responsible for increased glucagon secretion under conditions associated with hypoglycemia."}
{"id": "PMID:183997", "title": "Plasma immunoreactive glucagon fractions in four cases of glucagonoma: increased \"large glucagon-immunoreactivity\".", "content": "Immunoreactive glucagon (IRG) fractions from plasma of 8 normal subjects and 4 patients with glucagon secreting tumors were studied by gel filtration techniques on Bio Gel P--30 and Sephadex G--50 columns. The pancreatic glucagon specific anti serum (30K) of Unger was utilized to measure IRG. Columns were calibrated with labelled albumin, proinsulin, insulin and glucagon. Four peaks were defined in normal and tumor bearing patients: peak I (greater than 20 000 mol. wt.), peak II (primarily 9000 mol. wt.), peak III pancreatic glucagon (3500 mol. wt.) and peak IV small gucagon (less than 3500 mol. wt.). Glucagonoma patients differed from our normal and reported normal subjects in that peak II contained most of the circulating IRG. The percent of IRG associated with peak II was 9.5--31.5% in normals and 39.1--61.2% in glucagonomas. Glucagon-like biological activity in an isolated hepatocyte system was demonstrated for all peaks. However, relative to immunoreactivity, peak II showed reduced activity (25--33%). Immunoassay of dilutions of all peaks revealed the probability of immuno determinants identical with procine pancreatic glucagon. The presence of heterogenous IRG peaks with biological glucagon-like activity suggest that the larger molecules may be prohormones. Further, it is possible that specific elevation of peak II may be a diagnostic feature of glucagonomas.", "contents": "Plasma immunoreactive glucagon fractions in four cases of glucagonoma: increased \"large glucagon-immunoreactivity\". Immunoreactive glucagon (IRG) fractions from plasma of 8 normal subjects and 4 patients with glucagon secreting tumors were studied by gel filtration techniques on Bio Gel P--30 and Sephadex G--50 columns. The pancreatic glucagon specific anti serum (30K) of Unger was utilized to measure IRG. Columns were calibrated with labelled albumin, proinsulin, insulin and glucagon. Four peaks were defined in normal and tumor bearing patients: peak I (greater than 20 000 mol. wt.), peak II (primarily 9000 mol. wt.), peak III pancreatic glucagon (3500 mol. wt.) and peak IV small gucagon (less than 3500 mol. wt.). Glucagonoma patients differed from our normal and reported normal subjects in that peak II contained most of the circulating IRG. The percent of IRG associated with peak II was 9.5--31.5% in normals and 39.1--61.2% in glucagonomas. Glucagon-like biological activity in an isolated hepatocyte system was demonstrated for all peaks. However, relative to immunoreactivity, peak II showed reduced activity (25--33%). Immunoassay of dilutions of all peaks revealed the probability of immuno determinants identical with procine pancreatic glucagon. The presence of heterogenous IRG peaks with biological glucagon-like activity suggest that the larger molecules may be prohormones. Further, it is possible that specific elevation of peak II may be a diagnostic feature of glucagonomas."}
{"id": "PMID:183998", "title": "Catecholamine receptor sensitivity and the regulation of lipolysis in adult diabetes.", "content": "The sensitivity of alpha- and beta-adrenergic receptors, and the antilipolytic actions of prostaglandin E1 or insulin on adipose tissue of obese diabetic and non-diabetic subjects have been studied. Accumulation of cyclic AMP in adipose tissue and release of glycerol in response to several catecholamines (adrenaline, noradrenaline and isoprenaline) in the presence or absence of an alpha-adrenergic blocker (phentolamine) have been used to assess catecholamine receptor sensitivity. No differences in beta-receptor activity were observed between diabetics and non-diabetics, either on glycerol release or accumulation of cyclic AMP; alpha-receptor activity was also similar, except for significantly less accumulation of cyclic AMP in diabetic tissue incubated with noradrenaline and phentolamine (p less than 0.01). The antilipolytic action of prostaglandin E1 (at concentrations of 30 fM to 30 pM) on lipolysis (stimulated submaximally with isoprenaline, 10(-7) M) was similar in diabetic and control groups. The antilipolytic action of insulin (from 10(-10) to 10(-6) M) on lipolysis was also similar between the groups. It is concluded that neither disorders of the catecholamine receptor nor of the antiliolytic actions of prostaglandin E1 or insulin are responsible for the abnormalities of fatty acid metabolism in adult diabetes.", "contents": "Catecholamine receptor sensitivity and the regulation of lipolysis in adult diabetes. The sensitivity of alpha- and beta-adrenergic receptors, and the antilipolytic actions of prostaglandin E1 or insulin on adipose tissue of obese diabetic and non-diabetic subjects have been studied. Accumulation of cyclic AMP in adipose tissue and release of glycerol in response to several catecholamines (adrenaline, noradrenaline and isoprenaline) in the presence or absence of an alpha-adrenergic blocker (phentolamine) have been used to assess catecholamine receptor sensitivity. No differences in beta-receptor activity were observed between diabetics and non-diabetics, either on glycerol release or accumulation of cyclic AMP; alpha-receptor activity was also similar, except for significantly less accumulation of cyclic AMP in diabetic tissue incubated with noradrenaline and phentolamine (p less than 0.01). The antilipolytic action of prostaglandin E1 (at concentrations of 30 fM to 30 pM) on lipolysis (stimulated submaximally with isoprenaline, 10(-7) M) was similar in diabetic and control groups. The antilipolytic action of insulin (from 10(-10) to 10(-6) M) on lipolysis was also similar between the groups. It is concluded that neither disorders of the catecholamine receptor nor of the antiliolytic actions of prostaglandin E1 or insulin are responsible for the abnormalities of fatty acid metabolism in adult diabetes."}
{"id": "PMID:183999", "title": "Quantitative variations of three different lectin receptors as a function of establishment and metabolism of normal and leukaemic human cell lines.", "content": "Lectin binding on the cell surface was measured by the method of Kornfeld [16] using three tritiated lectins: Robinia pseudo acacia, Concanavalin A and Ricinus. It has been shown that the number of binding sites for Robinia and Con A decreases after the establishment of a leukaemic cell line, whereas the affinity constant increases for Robinia. The relationship between lectin binding and cell growth was carried out on 5 cell lines, 3 of leukaemic and 2 of normal origin. In all cases the maximum number of sites was determined at the time of doubling for the cell population; the affinity constant reciprocally decreases at this moment. For Robinia, a difference was found in both cell growth and the number of sites between an Epstein-Barr virus (EBV) negative leukaemic cell line and the other EBV positive cell lines. Lectins offer a quantitative method for measuring membrane structure variations during and after establishment of cell lines.", "contents": "Quantitative variations of three different lectin receptors as a function of establishment and metabolism of normal and leukaemic human cell lines. Lectin binding on the cell surface was measured by the method of Kornfeld [16] using three tritiated lectins: Robinia pseudo acacia, Concanavalin A and Ricinus. It has been shown that the number of binding sites for Robinia and Con A decreases after the establishment of a leukaemic cell line, whereas the affinity constant increases for Robinia. The relationship between lectin binding and cell growth was carried out on 5 cell lines, 3 of leukaemic and 2 of normal origin. In all cases the maximum number of sites was determined at the time of doubling for the cell population; the affinity constant reciprocally decreases at this moment. For Robinia, a difference was found in both cell growth and the number of sites between an Epstein-Barr virus (EBV) negative leukaemic cell line and the other EBV positive cell lines. Lectins offer a quantitative method for measuring membrane structure variations during and after establishment of cell lines."}
{"id": "PMID:184000", "title": "New concepts on the action of oestrogens in the uterus and the role of the eosinophil receptor system.", "content": "Two receptor systems for oestrogens have been demonstrated in the uterus: the cytosol-nuclear receptor system and the eosinophil receptor system. It has been proposed that the cytosol-nuclear receptor system mediates the genomic response to oestrogens in the uterus, while the eosinophil receptor system is thought to mediate the uterine edema and other early oestrogenic responses in the uterus. Cortisol is known to decrease drastically the number of eosinophils in the blood and therefore to limit their availability for migration to the uterus. The present results show that cortisol also drastically reduces both the oestrogen-induced uterine eosinophilia and the uterine wet weight responses, but does not interfere with the oestrogen-induced uterine RNA and protein increases. Oestradiol-17 beta has a higher affinity than oestriol for the cytosol-nuclear receptors and is now found to be the more potent oestrogen in inducing the genomic activation in the uterus. Estriol has a higher affinity than oestradiol-17 beta for the eosinophil receptors, and therefore, oestriol is the stronger oestrogen in inducing those oestrogenic effects which are mediated by the eosinophil receptor system. We conclude that the eosinophil receptor system for oestrogens is a new system, independent of Jensen's cytosol-nuclear receptor system, and this eosinophil receptor system is involved in the mechanism of oestrogen action in the uterus.", "contents": "New concepts on the action of oestrogens in the uterus and the role of the eosinophil receptor system. Two receptor systems for oestrogens have been demonstrated in the uterus: the cytosol-nuclear receptor system and the eosinophil receptor system. It has been proposed that the cytosol-nuclear receptor system mediates the genomic response to oestrogens in the uterus, while the eosinophil receptor system is thought to mediate the uterine edema and other early oestrogenic responses in the uterus. Cortisol is known to decrease drastically the number of eosinophils in the blood and therefore to limit their availability for migration to the uterus. The present results show that cortisol also drastically reduces both the oestrogen-induced uterine eosinophilia and the uterine wet weight responses, but does not interfere with the oestrogen-induced uterine RNA and protein increases. Oestradiol-17 beta has a higher affinity than oestriol for the cytosol-nuclear receptors and is now found to be the more potent oestrogen in inducing the genomic activation in the uterus. Estriol has a higher affinity than oestradiol-17 beta for the eosinophil receptors, and therefore, oestriol is the stronger oestrogen in inducing those oestrogenic effects which are mediated by the eosinophil receptor system. We conclude that the eosinophil receptor system for oestrogens is a new system, independent of Jensen's cytosol-nuclear receptor system, and this eosinophil receptor system is involved in the mechanism of oestrogen action in the uterus."}
{"id": "PMID:184001", "title": "Dynamics of eosinophils in the uterus after oestrogen administration.", "content": "To investigase the role of the eosinophil leukocytes in the early oestrogenic responses in the uterus, the kinetics of oestrogen-induced uterine eosinophilia and other parameters of oestrogen stimulation were studied at very early times. Uterine eosinophils increase as early as 5 min after an intravenous injection of oestradiol to immature rats, much earlier than several other changes in the early parameters of oestrogen stimulation. Large number of uterine eosinophils are found attached to the wall of small uterine blood vessels at early times. To elucidate the mechanisms involved in the specific attraction of eosinophils to the uterus in the presence of oestrogens, the in vivo localisation of oestrogens in the rat uterus at early times was studied using a radioautographic technique. Oestrogen receptors were found in the surface of eosinophils and in the wall of small uterine blood vessels. This simultaneous presence of both oestrogen receptors is proposed to explain the specific attachment of eosinophils to uterine blood vessels in the presence of oestrogens, which is the initial step toward eosinophil penetration into the uterus.", "contents": "Dynamics of eosinophils in the uterus after oestrogen administration. To investigase the role of the eosinophil leukocytes in the early oestrogenic responses in the uterus, the kinetics of oestrogen-induced uterine eosinophilia and other parameters of oestrogen stimulation were studied at very early times. Uterine eosinophils increase as early as 5 min after an intravenous injection of oestradiol to immature rats, much earlier than several other changes in the early parameters of oestrogen stimulation. Large number of uterine eosinophils are found attached to the wall of small uterine blood vessels at early times. To elucidate the mechanisms involved in the specific attraction of eosinophils to the uterus in the presence of oestrogens, the in vivo localisation of oestrogens in the rat uterus at early times was studied using a radioautographic technique. Oestrogen receptors were found in the surface of eosinophils and in the wall of small uterine blood vessels. This simultaneous presence of both oestrogen receptors is proposed to explain the specific attachment of eosinophils to uterine blood vessels in the presence of oestrogens, which is the initial step toward eosinophil penetration into the uterus."}
{"id": "PMID:184002", "title": "Effect of Sarkosyl on chromatin and viral RNA synthesis. The isolation of SV40 transcription complex.", "content": "The endogenous RNA polymerase activity of mouse nucleic is enhanced several-fold by the anionic detergent Sarkosyl. The action of Sarkosyl is exerted primarily on the alpha-amanitin sensitive form of the enzyme. This detergent causes the release of nearly all the protein associated with cellular DNA but does not release initiated RNA polymerase. Sarkosyl was also able to activate the RNA polymerase activity from mitotic cells, in which transcription of the highly condensed chromatin is minimal. The use of this anionic detergent has also permitted the extraction of a nucleoprotein complex from Simian Virus 40 (SV40) infected monkey cells. Molecular hybridization experiments have established the viral specificity of the RNA synthesized in vitro by the endogenous polymerase present in this complex.", "contents": "Effect of Sarkosyl on chromatin and viral RNA synthesis. The isolation of SV40 transcription complex. The endogenous RNA polymerase activity of mouse nucleic is enhanced several-fold by the anionic detergent Sarkosyl. The action of Sarkosyl is exerted primarily on the alpha-amanitin sensitive form of the enzyme. This detergent causes the release of nearly all the protein associated with cellular DNA but does not release initiated RNA polymerase. Sarkosyl was also able to activate the RNA polymerase activity from mitotic cells, in which transcription of the highly condensed chromatin is minimal. The use of this anionic detergent has also permitted the extraction of a nucleoprotein complex from Simian Virus 40 (SV40) infected monkey cells. Molecular hybridization experiments have established the viral specificity of the RNA synthesized in vitro by the endogenous polymerase present in this complex."}
{"id": "PMID:184004", "title": "Acceleration of hepatocarcinogenesis of 2,7-bis(acetamido)fluorene by carbon tetrachloride and time relation of treatment.", "content": "The role of period between administration of CCl4 and feeding of 2,7-bis-(acetamido)fluorene in the hepatocarcinogenesis of mice was analyzed by using 14 groups of different feeding schedules. Simultaneous treatment with CCl4 and either continuous or intermittent feeding of 2,7-bis(acetamido)fluorene increased the average number of hepatic nodules and the incidence of hepatomas, while separation of 8-week feeding of 2,7-bis(acetamido)fluorene from 8 week treatment with CCl4 did not accelerate the hepatocarcinogenesis. Alternate treatment with CCl4 and 2,7-bis(acetamido)fluorene increased the average number of hepatic nodules but failed to induce hepatomas. Allyl alcohol, which is a hepatotoxic substance as is CCl4, also failed to accelerate hepatocarcinogenesis of 2,7-bis(acetamido)fluorene. Concerning the feeding schedule of 2,7-bis(acetamido)fluorene alone, the intermittent one-week feeding of the carcinogen with 3-week intervals decreased the average number of hepatic nodules as compared with the continuous feeding of the carcinogen.", "contents": "Acceleration of hepatocarcinogenesis of 2,7-bis(acetamido)fluorene by carbon tetrachloride and time relation of treatment. The role of period between administration of CCl4 and feeding of 2,7-bis-(acetamido)fluorene in the hepatocarcinogenesis of mice was analyzed by using 14 groups of different feeding schedules. Simultaneous treatment with CCl4 and either continuous or intermittent feeding of 2,7-bis(acetamido)fluorene increased the average number of hepatic nodules and the incidence of hepatomas, while separation of 8-week feeding of 2,7-bis(acetamido)fluorene from 8 week treatment with CCl4 did not accelerate the hepatocarcinogenesis. Alternate treatment with CCl4 and 2,7-bis(acetamido)fluorene increased the average number of hepatic nodules but failed to induce hepatomas. Allyl alcohol, which is a hepatotoxic substance as is CCl4, also failed to accelerate hepatocarcinogenesis of 2,7-bis(acetamido)fluorene. Concerning the feeding schedule of 2,7-bis(acetamido)fluorene alone, the intermittent one-week feeding of the carcinogen with 3-week intervals decreased the average number of hepatic nodules as compared with the continuous feeding of the carcinogen."}
{"id": "PMID:184005", "title": "Mixed mesodermal tumor of the uterine body: relationship between histology and survival.", "content": "A clinico-pathological study of 20 cases of mixed mesodermal tumor of the uterine body is reported. Fifteen tumors were found after menopause. The mean age of all cases was 55.5 years. Histologically, mixed mesodermal tumors consisted of two different components; epithelial and sarcomatous patterns, in 18 cases. Mixed mesodermal tumors in four of the 18 cases had no adenocarcinomatous elements but showed a benign glandular structure. In the remaining two tumors, epithelial patterns were absent and only heterologous sarcomatous elements were found. Ten of the patients had received hysterectomy more than five years ago. Three of these patients, having no malignant but benign epithelial component, showed a relatively good prognosis. Adenocarcinomatous elements were found in six cases, and four patients with carcinomatous elements had poor prognosis. It can be stated that the prognosis of mixed mesodermal tumor chiefly depends on the malignancy of epithelial components, when comparing the prognosis of the tumors at the same clinical stage. On the other hand, sarcomatous elements are not likely to reflect the prognosis of the tumors. Mixed mesodermal tumor is monodermal in origin, namely, mesodermal origin, and might arise from the Muellerian duct or more primitive mesodermal tissue.", "contents": "Mixed mesodermal tumor of the uterine body: relationship between histology and survival. A clinico-pathological study of 20 cases of mixed mesodermal tumor of the uterine body is reported. Fifteen tumors were found after menopause. The mean age of all cases was 55.5 years. Histologically, mixed mesodermal tumors consisted of two different components; epithelial and sarcomatous patterns, in 18 cases. Mixed mesodermal tumors in four of the 18 cases had no adenocarcinomatous elements but showed a benign glandular structure. In the remaining two tumors, epithelial patterns were absent and only heterologous sarcomatous elements were found. Ten of the patients had received hysterectomy more than five years ago. Three of these patients, having no malignant but benign epithelial component, showed a relatively good prognosis. Adenocarcinomatous elements were found in six cases, and four patients with carcinomatous elements had poor prognosis. It can be stated that the prognosis of mixed mesodermal tumor chiefly depends on the malignancy of epithelial components, when comparing the prognosis of the tumors at the same clinical stage. On the other hand, sarcomatous elements are not likely to reflect the prognosis of the tumors. Mixed mesodermal tumor is monodermal in origin, namely, mesodermal origin, and might arise from the Muellerian duct or more primitive mesodermal tissue."}
{"id": "PMID:184006", "title": "Effect of Clostridium toxoids, especially of Clostridium perfringens toxoid, on mouse transplanted tumors.", "content": "The antitumor activities of toxoids of Clostridium perfringens, C. nouyi, C. septicum, and C. tetani were tested against sarcoma-180 and Ehrlich carcinoma. Among them, C. perfringens toxoid showed a high antitumor activity against the growth of the implanted sarcoma-180 ascites form. The results of the inhibiting effect of C. perfringens toxoid on Nakahara-Tokuzen-Fukuoka (NTF) reticulum cell sarcoma and methylcholanthrene-induced fibrosarcoma were also described.", "contents": "Effect of Clostridium toxoids, especially of Clostridium perfringens toxoid, on mouse transplanted tumors. The antitumor activities of toxoids of Clostridium perfringens, C. nouyi, C. septicum, and C. tetani were tested against sarcoma-180 and Ehrlich carcinoma. Among them, C. perfringens toxoid showed a high antitumor activity against the growth of the implanted sarcoma-180 ascites form. The results of the inhibiting effect of C. perfringens toxoid on Nakahara-Tokuzen-Fukuoka (NTF) reticulum cell sarcoma and methylcholanthrene-induced fibrosarcoma were also described."}
{"id": "PMID:184007", "title": "Beta-glucuronidase isozyme patterns of experimental hepatomas of rats.", "content": "Beta-Glucuronidase isozymes in rat tissues were separated by electrophoresis on cellulose acetate membranes. Using this method, beta-glucuronidase isozyme patterns were studied in normal rat liver and experimental hepatomas with different growth rates. Changes of isozyme patterns during postnatal development were also studied in rat liver. Normal rat liver contained six types of beta-glucuronidase, numbered I to VI in order to decreasing mobility to the cathode. Type II beta-glucuronidase stained most intensely and was detected in all the cells examined. The isozyme patterns of Morris hepatomas, which are slowly growing and not highly deviated, resembled that of normal rat liver but lacked definite Type III beta-glucuronidase. Yoshida ascites hepatomas, which are rapidly growing and highly deviated, contained only Type II, but some had Types II, V, and VI beta-glucuronidase. Embryonal liver just before birth contained only Type II, but with increase in activity during development after birth, minor bands of Type I and Types III  to VI beta-glucuronidase appeared successively to complete the adult pattern.", "contents": "Beta-glucuronidase isozyme patterns of experimental hepatomas of rats. Beta-Glucuronidase isozymes in rat tissues were separated by electrophoresis on cellulose acetate membranes. Using this method, beta-glucuronidase isozyme patterns were studied in normal rat liver and experimental hepatomas with different growth rates. Changes of isozyme patterns during postnatal development were also studied in rat liver. Normal rat liver contained six types of beta-glucuronidase, numbered I to VI in order to decreasing mobility to the cathode. Type II beta-glucuronidase stained most intensely and was detected in all the cells examined. The isozyme patterns of Morris hepatomas, which are slowly growing and not highly deviated, resembled that of normal rat liver but lacked definite Type III beta-glucuronidase. Yoshida ascites hepatomas, which are rapidly growing and highly deviated, contained only Type II, but some had Types II, V, and VI beta-glucuronidase. Embryonal liver just before birth contained only Type II, but with increase in activity during development after birth, minor bands of Type I and Types III  to VI beta-glucuronidase appeared successively to complete the adult pattern."}
{"id": "PMID:184008", "title": "Increased susceptibility to carcinoma of the liver in rats with one kidney ingesting N-4-(4'-fluorobiphenyl) acetamide.", "content": "The role of the kidneys in hepatic carcinogenesis was studied in inbred Buffalo strain male rats ingesting 0.04% N-4-(4'-flourobiphenyl) acetamide in the diet. Experimental groups were made up of male rats with both kidneys intact and male rats with the left kidney removed. The incidence of carcinomas of the liver and the number of rats with large carcinomas, multiple carcinomas, poorly differentiated and undifferentiated carcinomas, and metastases were greater in rats with a uninephrectomy. Apparently the animals with one kidney removed were unable to secrete the metabolites of N-4-(4'-fluorobiphenyl) acetamide as readily as the rats with both kidneys.", "contents": "Increased susceptibility to carcinoma of the liver in rats with one kidney ingesting N-4-(4'-fluorobiphenyl) acetamide. The role of the kidneys in hepatic carcinogenesis was studied in inbred Buffalo strain male rats ingesting 0.04% N-4-(4'-flourobiphenyl) acetamide in the diet. Experimental groups were made up of male rats with both kidneys intact and male rats with the left kidney removed. The incidence of carcinomas of the liver and the number of rats with large carcinomas, multiple carcinomas, poorly differentiated and undifferentiated carcinomas, and metastases were greater in rats with a uninephrectomy. Apparently the animals with one kidney removed were unable to secrete the metabolites of N-4-(4'-fluorobiphenyl) acetamide as readily as the rats with both kidneys."}
{"id": "PMID:184009", "title": "Protection by propylthiouracil against carbon tetrachloride-induced liver damage.", "content": "Rats given a single intragastric dose of carbon tetrachloride (CCl4), 0.25, 0.50, or 1.0 ml per kg) showed a dose-dependent increase in SGOT, serum ornithine carbamyltransferase, and liver necrosis (graded histologically as 0 to 4+) 24 hr after the treatment. Daily intubation with propylthiouracil (PTU) for 10 days in doses of 5 to 50 mg per kg significantly reduced the elevation of SGOT activity, completely suppressed the serum ornithine carbamyltransferase changes, and reduced the degree of necrosis found 24 hr after the intragastric administration of CCl4. Similar protection was found when CCl4 was given intraperitoneally. When PTU was given in liguid diets for 6 days, protection against CCl4 was increased. PTU did not affect the absorption or covalent binding of 14CCl4 to lipids or proteins. Also, control and PTU-treated rats did not differ with respect to glucose-6-phosphatase activity and conjugated diene production after CCl4. Thus, it has been observed that PTU affords partial protection against some end-stage consequences of CCl4 liver injury such as cell necrosis and release of intracellular enzymes. However, PTU afforded no protection against early chemical effects such as covalent binding of CCl4 carbon, lipid peroxidation, or loss of glucose-6-phosphatase. Therefore, it is concluded that the mechanism of the PTU effect comes into play after the initial effects of CCl4 are exerted and in some unknown manner modulates the expression of these early effects.", "contents": "Protection by propylthiouracil against carbon tetrachloride-induced liver damage. Rats given a single intragastric dose of carbon tetrachloride (CCl4), 0.25, 0.50, or 1.0 ml per kg) showed a dose-dependent increase in SGOT, serum ornithine carbamyltransferase, and liver necrosis (graded histologically as 0 to 4+) 24 hr after the treatment. Daily intubation with propylthiouracil (PTU) for 10 days in doses of 5 to 50 mg per kg significantly reduced the elevation of SGOT activity, completely suppressed the serum ornithine carbamyltransferase changes, and reduced the degree of necrosis found 24 hr after the intragastric administration of CCl4. Similar protection was found when CCl4 was given intraperitoneally. When PTU was given in liguid diets for 6 days, protection against CCl4 was increased. PTU did not affect the absorption or covalent binding of 14CCl4 to lipids or proteins. Also, control and PTU-treated rats did not differ with respect to glucose-6-phosphatase activity and conjugated diene production after CCl4. Thus, it has been observed that PTU affords partial protection against some end-stage consequences of CCl4 liver injury such as cell necrosis and release of intracellular enzymes. However, PTU afforded no protection against early chemical effects such as covalent binding of CCl4 carbon, lipid peroxidation, or loss of glucose-6-phosphatase. Therefore, it is concluded that the mechanism of the PTU effect comes into play after the initial effects of CCl4 are exerted and in some unknown manner modulates the expression of these early effects."}
{"id": "PMID:184011", "title": "Male pseudohermaphroditism consistent with 17,20-desmolase deficiency.", "content": "A 16-year-old phenotypic female with XY genotype presented an unusual form of nonfamilial male pseudohermaphroditism. Seemingly a normal girl during childhood, the patient failed to undergo pubertal changes presenting with scant pubic hair, absent axillary hair, lack of breast development, retarded bone age and primary amenorrhea. Neither uterus nor adnexa were palpable above the blind-ending vagina. Serum testosterone and estradiol were barely detectable by radioimmunoassay, while LH and FSH reached castrate levels. Two small testes were removed from the pelvic sidewalls which, on biopsy, showed atrophy and hyalinization of seminiferous tubules, but clusters of Leydig cells without signs of hypertrophy or hyperplasia. Administration of testosterone resulted in urinary nitrogen retention and a decrease in serum LH and FSH. Radioimmunoassay of various serum or plasma steroids and gas chromatographic determination of urinary steroids prior to and following ACTH stimulation yielded results which permitted to rule out 20,22-desmolase, 3beta-hydroxysteroid dehydrogenase, 17-hydroxylase and 17beta-hydroxysteroid dehydrogenase deficiency. Low plasma dehydroepiandrosterone sulfate (DHEA-S) and androstenedione (delta4 A) concentrations, low urinary 17-ketosteroid and particularly low dehydroepiandrosterone (DHEA) excretion and the minimal rise of plasma DHEA-S and delta4 A and of urinary DHEA in response to ACTH in conjunction with a normal response of other serum and urinary C-21 steroids are consistent with 17,20-desmolase deficiency. Direct confirmation of this defect, however, seems impossible in the absence of in vitro studies of testicular steroidogenesis.", "contents": "Male pseudohermaphroditism consistent with 17,20-desmolase deficiency. A 16-year-old phenotypic female with XY genotype presented an unusual form of nonfamilial male pseudohermaphroditism. Seemingly a normal girl during childhood, the patient failed to undergo pubertal changes presenting with scant pubic hair, absent axillary hair, lack of breast development, retarded bone age and primary amenorrhea. Neither uterus nor adnexa were palpable above the blind-ending vagina. Serum testosterone and estradiol were barely detectable by radioimmunoassay, while LH and FSH reached castrate levels. Two small testes were removed from the pelvic sidewalls which, on biopsy, showed atrophy and hyalinization of seminiferous tubules, but clusters of Leydig cells without signs of hypertrophy or hyperplasia. Administration of testosterone resulted in urinary nitrogen retention and a decrease in serum LH and FSH. Radioimmunoassay of various serum or plasma steroids and gas chromatographic determination of urinary steroids prior to and following ACTH stimulation yielded results which permitted to rule out 20,22-desmolase, 3beta-hydroxysteroid dehydrogenase, 17-hydroxylase and 17beta-hydroxysteroid dehydrogenase deficiency. Low plasma dehydroepiandrosterone sulfate (DHEA-S) and androstenedione (delta4 A) concentrations, low urinary 17-ketosteroid and particularly low dehydroepiandrosterone (DHEA) excretion and the minimal rise of plasma DHEA-S and delta4 A and of urinary DHEA in response to ACTH in conjunction with a normal response of other serum and urinary C-21 steroids are consistent with 17,20-desmolase deficiency. Direct confirmation of this defect, however, seems impossible in the absence of in vitro studies of testicular steroidogenesis."}
{"id": "PMID:184016", "title": "[Treatment of acne vulgaris in practice].", "content": "The aim of all acne therapy is sebostasis and treatment of Corynebacterium acnes as well as secondary infected postular changes. After discussion of Tretinoin (Retinoic acid)-treatment it is reported about 35 cases of acne vulgaris which were treated with the combination of Hexachlorophenspiritus 1%,Silicatgel locally and Tetracycline orally. The good results of this treatment are reported. Side effects have not been observed.", "contents": "[Treatment of acne vulgaris in practice]. The aim of all acne therapy is sebostasis and treatment of Corynebacterium acnes as well as secondary infected postular changes. After discussion of Tretinoin (Retinoic acid)-treatment it is reported about 35 cases of acne vulgaris which were treated with the combination of Hexachlorophenspiritus 1%,Silicatgel locally and Tetracycline orally. The good results of this treatment are reported. Side effects have not been observed."}
{"id": "PMID:184017", "title": "[Studies on the strain on drivers during high-speed driving].", "content": "In modern industrial countries the technological progress has shifted the occupational stress to the psychomental sphere. In the course of this alteration the number of work places with driving, controlling, and monitoring increased considerably. On 10 engine-drivers during high-speed driving from 210 to 250 km/h heart rate and electrocardiogram were monitored continuously. The blood pressure was measured intermittently. The elimination rate of catecholamines in urine, and the levels of cyclic AMP and catechol-O-methyltransferase in plasma were determined in reference to the trial to quantify the psychomental strain by biochemical parameters. In consequence of the individual affective conditions of the engine-drivers it has been attempted to scale the subjective strain.", "contents": "[Studies on the strain on drivers during high-speed driving]. In modern industrial countries the technological progress has shifted the occupational stress to the psychomental sphere. In the course of this alteration the number of work places with driving, controlling, and monitoring increased considerably. On 10 engine-drivers during high-speed driving from 210 to 250 km/h heart rate and electrocardiogram were monitored continuously. The blood pressure was measured intermittently. The elimination rate of catecholamines in urine, and the levels of cyclic AMP and catechol-O-methyltransferase in plasma were determined in reference to the trial to quantify the psychomental strain by biochemical parameters. In consequence of the individual affective conditions of the engine-drivers it has been attempted to scale the subjective strain."}
{"id": "PMID:184019", "title": "[Climacteric disturbances. 2. Therapy of climacteric disturbances].", "content": "After defining the terms climacterium and menopause the causes of climacteric disturbances are explained. During the premenopausal stage disturbances of the cycle are prevailing, caused by an insufficiency of the corpus luteum. Of climacteric disturbances should be spoken only after menopause. They are divided into: vegetative disturbances, troubles of metabolism, cardiovascular dysregulation, psychic deviations, sexual troubles and changes of the skin. The therapy of disturbances during the premenopausal stage mainly consists of the substitution of progesterone or in a cycle-like estrogen-progesterone-therapy. In the premenopausal stage estrogens are the therapy of choice. Among orally efficient estrogens the conjugated estrogen and the estradiol-valerianat are preferred. Side-effects and contraindications are discussed in detail. Among gynecologists there exists no disagreement about the necessity of therapy of serious climacteric disturbances, the opinions about prophylactic estrogen-therapy in women differ.", "contents": "[Climacteric disturbances. 2. Therapy of climacteric disturbances]. After defining the terms climacterium and menopause the causes of climacteric disturbances are explained. During the premenopausal stage disturbances of the cycle are prevailing, caused by an insufficiency of the corpus luteum. Of climacteric disturbances should be spoken only after menopause. They are divided into: vegetative disturbances, troubles of metabolism, cardiovascular dysregulation, psychic deviations, sexual troubles and changes of the skin. The therapy of disturbances during the premenopausal stage mainly consists of the substitution of progesterone or in a cycle-like estrogen-progesterone-therapy. In the premenopausal stage estrogens are the therapy of choice. Among orally efficient estrogens the conjugated estrogen and the estradiol-valerianat are preferred. Side-effects and contraindications are discussed in detail. Among gynecologists there exists no disagreement about the necessity of therapy of serious climacteric disturbances, the opinions about prophylactic estrogen-therapy in women differ."}
{"id": "PMID:184022", "title": "[Experiences with depot-ACTH (Tetracosactide) in bronchial obstruction].", "content": "The difficulties of long term treatment of chronic obstructive lung disease demand knowledge and use of every reasonable therapeutic regimen. In this study effectivity and side effects of Depot-ACTH (Tetracosactid) are presented. The main indications for the use of Depot-ACTH seem to be the uneffectiveness of usual therapy and the attempt of avoiding or reducing corticosteroids. The study confirms the excellent usefulness of Depot-ACTH which did not diminish during long-term application. The side effects are rare and mostly inferior. Only allergic reactions may be serious and must be accounted for.", "contents": "[Experiences with depot-ACTH (Tetracosactide) in bronchial obstruction]. The difficulties of long term treatment of chronic obstructive lung disease demand knowledge and use of every reasonable therapeutic regimen. In this study effectivity and side effects of Depot-ACTH (Tetracosactid) are presented. The main indications for the use of Depot-ACTH seem to be the uneffectiveness of usual therapy and the attempt of avoiding or reducing corticosteroids. The study confirms the excellent usefulness of Depot-ACTH which did not diminish during long-term application. The side effects are rare and mostly inferior. Only allergic reactions may be serious and must be accounted for."}
{"id": "PMID:184024", "title": "[Quantitative analysis of characteristics of the negative feedback regulation of ACTH secretion under stress (author's transl)].", "content": "Quantitative characteristics and a plausible mechanism of rapid rate-sensitive feedback inhibition of the CRF-ACTH-corticoid system were studied using Nembutal-anesthetized rats. The plasma corticosterone levels were varied by continuous infusion of corticosterone through a lateral caudal vein. The response to an intravenous injection of histamine (as a stressor) was distinctly inhibited in two phases of the dynamics of plasma corticosterone; one in its rapidly increasing phase (rapid rate-sensitive feedback inhibition) and the other, two hours or more after a high plasma steroid level has been attained (late level-sensitive feedback inhibition). On the other hand, there was no such inhibition between these two phases. A quantitative approach made by repeated blood sampling from single rats revealed that the critical rate of elevation of plasma corticosterone at which the rate-sensitive feedback inhibition). On the other hand, there was no such inhibition between these two phases. A quantitative approach made by repeated blood sampling from single rats revealed that the critical rate of elevation of plasma corticosterone at which the rate-sensitive inhibition begins to obviously occur was 4-6 mug%/min. Even with increasing strength of stress, the absolute size of inhibition at a fixed rate of elevation in plasma corticosterone remained almost the same. The increase in the median eminence-CRF activity, known to occur after stress, was effectively suppressed during the operation of rapid feedback inhibition. In addition, in brain noradrenaline-depleted rats, the rapid component in the feedback inhibition was thoroughly abolished, leaving the late component intact, while the opposite way in sorotonin-reduced rats. This finding suggests an involvement of brain biogenic amines in the negative feedback regulation of ACTH secretion in a rather specific way. Finally, on the basis of these results, a plausible model for the rapid rate-sensitive feedback regulation of ACTH secretion under stress was considered.", "contents": "[Quantitative analysis of characteristics of the negative feedback regulation of ACTH secretion under stress (author's transl)]. Quantitative characteristics and a plausible mechanism of rapid rate-sensitive feedback inhibition of the CRF-ACTH-corticoid system were studied using Nembutal-anesthetized rats. The plasma corticosterone levels were varied by continuous infusion of corticosterone through a lateral caudal vein. The response to an intravenous injection of histamine (as a stressor) was distinctly inhibited in two phases of the dynamics of plasma corticosterone; one in its rapidly increasing phase (rapid rate-sensitive feedback inhibition) and the other, two hours or more after a high plasma steroid level has been attained (late level-sensitive feedback inhibition). On the other hand, there was no such inhibition between these two phases. A quantitative approach made by repeated blood sampling from single rats revealed that the critical rate of elevation of plasma corticosterone at which the rate-sensitive feedback inhibition). On the other hand, there was no such inhibition between these two phases. A quantitative approach made by repeated blood sampling from single rats revealed that the critical rate of elevation of plasma corticosterone at which the rate-sensitive inhibition begins to obviously occur was 4-6 mug%/min. Even with increasing strength of stress, the absolute size of inhibition at a fixed rate of elevation in plasma corticosterone remained almost the same. The increase in the median eminence-CRF activity, known to occur after stress, was effectively suppressed during the operation of rapid feedback inhibition. In addition, in brain noradrenaline-depleted rats, the rapid component in the feedback inhibition was thoroughly abolished, leaving the late component intact, while the opposite way in sorotonin-reduced rats. This finding suggests an involvement of brain biogenic amines in the negative feedback regulation of ACTH secretion in a rather specific way. Finally, on the basis of these results, a plausible model for the rapid rate-sensitive feedback regulation of ACTH secretion under stress was considered."}
{"id": "PMID:184025", "title": "[Analysis of dynamics of corticotropin-releasing factor (CRF) activity in the rat hypothalamus under stress].", "content": "Obviously, the analysis of dynamic changes in the hypothalamic activity of corticotropin-releasing factor (CRF) is essential for understanding of the central regulatory mechanism of ACTH secretion. However, the significance of the changes in CRF activity will be extremely lessened if the effect of CRF per se be modified at the pituitary level. In fact, Yates et al. (1971) reported that the CRF effect was potentiated by the presence of vasopressin. Therefore, in this study we attempted first to determine if vasopressin does potentiate the CRF action. Next, we analyzed some aspects of CRF dynamics in the rat hypothalamus under prolonged stress. (1) Potentiation of CRF action by vasopressin. This possibility was examined by the following approaches: i) Adrenocortical responses to various mild stressors (exposure to sound, i.p. injection of saline solution, tail cut) were greater in dehydrated rats than in normal controls. ii) Similarly, the adrenocortical response to intravenous injection of stalk-median eminence extract (SME) through the tail vein under Nembutal anesthesia was larger in the dehydrated rat than in control. iii) Prior to SME administration, vasopressin in a subthreshold dose was injected intravenously to assay rats pretreated with chlorpromazine (CPZ)-morphine (M)-Nembutal (Nb). The adrenocortical response to SME, injected into the carotid artery 1 min later, was found significantly to increase due to prior administration of vasopressin. iv) However, no potentiating effect of vasopressin  was observed when SME and vasopressin (4 mU) were placed stimultaneously into the anterior pituitary tissue by the intrapituitary injection technique. v) In addition, no potentiating effect was observed in vitro incubation experiments under varying incubation conditions. Thus, it was shown that vasopressin has some potentiating effect on the stress response in vivo, but the effect is not at the pituitary level.  (II) Analysis of dynamic changes in hypothalamic CRF activity. CRF activity was estimated by the intrapituitary injection method of Hiroshige, the plasma ACTH and corticosterone levels being followed simultaneously. Plasma ACTH was determined by radioimmunoassay partly with RCC-RIA Kit, and partly with ACTH antisera (kindly supplied by Dr. W.F. Ganong) by the method of Berson and Yalow. i) In intact normal rats, the response pattern of hypothalamic CRF activity under etherlaparotomy stress was characteristically biphasic, i.e., composed of rapid and slow phases, while the plasma ACTH and corticosterone showed a sustained high level over a 2 hr of observation period.", "contents": "[Analysis of dynamics of corticotropin-releasing factor (CRF) activity in the rat hypothalamus under stress]. Obviously, the analysis of dynamic changes in the hypothalamic activity of corticotropin-releasing factor (CRF) is essential for understanding of the central regulatory mechanism of ACTH secretion. However, the significance of the changes in CRF activity will be extremely lessened if the effect of CRF per se be modified at the pituitary level. In fact, Yates et al. (1971) reported that the CRF effect was potentiated by the presence of vasopressin. Therefore, in this study we attempted first to determine if vasopressin does potentiate the CRF action. Next, we analyzed some aspects of CRF dynamics in the rat hypothalamus under prolonged stress. (1) Potentiation of CRF action by vasopressin. This possibility was examined by the following approaches: i) Adrenocortical responses to various mild stressors (exposure to sound, i.p. injection of saline solution, tail cut) were greater in dehydrated rats than in normal controls. ii) Similarly, the adrenocortical response to intravenous injection of stalk-median eminence extract (SME) through the tail vein under Nembutal anesthesia was larger in the dehydrated rat than in control. iii) Prior to SME administration, vasopressin in a subthreshold dose was injected intravenously to assay rats pretreated with chlorpromazine (CPZ)-morphine (M)-Nembutal (Nb). The adrenocortical response to SME, injected into the carotid artery 1 min later, was found significantly to increase due to prior administration of vasopressin. iv) However, no potentiating effect of vasopressin  was observed when SME and vasopressin (4 mU) were placed stimultaneously into the anterior pituitary tissue by the intrapituitary injection technique. v) In addition, no potentiating effect was observed in vitro incubation experiments under varying incubation conditions. Thus, it was shown that vasopressin has some potentiating effect on the stress response in vivo, but the effect is not at the pituitary level.  (II) Analysis of dynamic changes in hypothalamic CRF activity. CRF activity was estimated by the intrapituitary injection method of Hiroshige, the plasma ACTH and corticosterone levels being followed simultaneously. Plasma ACTH was determined by radioimmunoassay partly with RCC-RIA Kit, and partly with ACTH antisera (kindly supplied by Dr. W.F. Ganong) by the method of Berson and Yalow. i) In intact normal rats, the response pattern of hypothalamic CRF activity under etherlaparotomy stress was characteristically biphasic, i.e., composed of rapid and slow phases, while the plasma ACTH and corticosterone showed a sustained high level over a 2 hr of observation period."}
{"id": "PMID:184026", "title": "The binding by an NAD-affinity matrix of contaminating dehydrogenases in cytochrome c oxidase preparations.", "content": "An NAD-matrix is capable of the separation of three contaminant reductase activities from highly purified beef heart cytochrome c oxidase. Non-specific binding of cytochrome c oxidase occurs as well. When the matrix is saturated with respect to the non-specific binding, continued binding of the reductases can be observed. As a consequence of equilibration with the matrix, the turnover numbers of the unbound cytochrome c oxidase are increased.", "contents": "The binding by an NAD-affinity matrix of contaminating dehydrogenases in cytochrome c oxidase preparations. An NAD-matrix is capable of the separation of three contaminant reductase activities from highly purified beef heart cytochrome c oxidase. Non-specific binding of cytochrome c oxidase occurs as well. When the matrix is saturated with respect to the non-specific binding, continued binding of the reductases can be observed. As a consequence of equilibration with the matrix, the turnover numbers of the unbound cytochrome c oxidase are increased."}
{"id": "PMID:184027", "title": "[Concanavalin A induced changes of lymphocyte p-nitrophenylphosphatase (author's transl)].", "content": "The effect of K+, Na+, Mg2+ and ATP on the p-nitrophenylphosphatase activity was investigated. As an enzyme preparation a microsomal fraction of sheep lymphocytes was used. Low concentrations of Mg2+, K+ and Na+ increased, whereas high concentrations decreased the enzyme activity. There was an inhibition of activity by ATP without Na+ in the incubation medium and an increase of enzyme activity at low K:Na-ratio. By concanavalin A in a concentration of 15 mug/ml the p-nitrophenylphosphatase activity was increased in intact cells and the microsomal fraction for 30-40%. The activation was not Na+, K+, Mg2+, p-nitrophenylphosphate or ATP dependent.", "contents": "[Concanavalin A induced changes of lymphocyte p-nitrophenylphosphatase (author's transl)]. The effect of K+, Na+, Mg2+ and ATP on the p-nitrophenylphosphatase activity was investigated. As an enzyme preparation a microsomal fraction of sheep lymphocytes was used. Low concentrations of Mg2+, K+ and Na+ increased, whereas high concentrations decreased the enzyme activity. There was an inhibition of activity by ATP without Na+ in the incubation medium and an increase of enzyme activity at low K:Na-ratio. By concanavalin A in a concentration of 15 mug/ml the p-nitrophenylphosphatase activity was increased in intact cells and the microsomal fraction for 30-40%. The activation was not Na+, K+, Mg2+, p-nitrophenylphosphate or ATP dependent."}
{"id": "PMID:184028", "title": "Inactivation of yeast enzymes by proteinase A and B and carboxypeptidase Y from yeast.", "content": "Changes in the activities of 15 different enzymes during incubation of a crude yeast extract with the purified yeast proteinases A and B, and carboxypeptidase Y, respectively, have been measured. The spectrum of action of the three proteinases on the enzymes measured differs significantly, increasing or decreasing their activities or having no effect. Incubation of purified cytoplasmic malate dehydrogenase or purified mitochondrial malate dehydrogenase with proteinases A and B results in selective inactivation of the cytoplasmic enzyme, whereas the mitochondrial activity is not affected. Carboxypeptidase Y has no effect on the activity of either dehydrogenase. The results support the idea of selective proteolysis as the mechanism of the earlier observed inactivation of cytoplasmic malate dehydrogenase, initiated by the addition of glucose to intact yeast cells grown on acetate as carbon source (\"glucose effect\").", "contents": "Inactivation of yeast enzymes by proteinase A and B and carboxypeptidase Y from yeast. Changes in the activities of 15 different enzymes during incubation of a crude yeast extract with the purified yeast proteinases A and B, and carboxypeptidase Y, respectively, have been measured. The spectrum of action of the three proteinases on the enzymes measured differs significantly, increasing or decreasing their activities or having no effect. Incubation of purified cytoplasmic malate dehydrogenase or purified mitochondrial malate dehydrogenase with proteinases A and B results in selective inactivation of the cytoplasmic enzyme, whereas the mitochondrial activity is not affected. Carboxypeptidase Y has no effect on the activity of either dehydrogenase. The results support the idea of selective proteolysis as the mechanism of the earlier observed inactivation of cytoplasmic malate dehydrogenase, initiated by the addition of glucose to intact yeast cells grown on acetate as carbon source (\"glucose effect\")."}
{"id": "PMID:184029", "title": "A model for program evaluation in a unitized setting.", "content": "The unitized psychiatric hospital poses unique problems for the design of successful program evaluation systems. Using the model of program evaluation in operation at the Harlem Valley Psychiatric Center in New York, the authors describe what they have found to be essential components of a successful evaluation system, including methods of data input, processing, and feedback. Also discussed are the roles of key personnel and the utilization of data by clinical and administrative staff. The reasons for success of the system are discussed, as well as the potential role of program evaluation in integrating services, training, and administration of the facility.", "contents": "A model for program evaluation in a unitized setting. The unitized psychiatric hospital poses unique problems for the design of successful program evaluation systems. Using the model of program evaluation in operation at the Harlem Valley Psychiatric Center in New York, the authors describe what they have found to be essential components of a successful evaluation system, including methods of data input, processing, and feedback. Also discussed are the roles of key personnel and the utilization of data by clinical and administrative staff. The reasons for success of the system are discussed, as well as the potential role of program evaluation in integrating services, training, and administration of the facility."}
{"id": "PMID:184030", "title": "Localisation of the human ABO: Np-1: AK-1 linkage group by regional assignment of AK-1 to 9q34.", "content": "Quantitative red cell adenylate kinase (AK-1) assay has been used in 8 patients with partial duplication or deletion of chromosome 9 in an attempt to find the precise intrachromosomal location of the structural gene locus. All regions of chromosome 9 are represented in abnormal dosage in at least one patient. A 43% increase in AK-1 activity was found to be associated with duplication of the terminal band of the long arm of chromosome 9. Duplication of all other parts of chromosome 9 were associated with normal enzyme activity. These findings not only confirm the assignment of the AK-1 locus to chromosome 9 made previously in somatic cell hybrids, but suggest a more precise assignment to region 9q33 leads to qter. This places the ABO:Np-1:AK-1 linkage group at the distal end of the long arm of chromosome 9.", "contents": "Localisation of the human ABO: Np-1: AK-1 linkage group by regional assignment of AK-1 to 9q34. Quantitative red cell adenylate kinase (AK-1) assay has been used in 8 patients with partial duplication or deletion of chromosome 9 in an attempt to find the precise intrachromosomal location of the structural gene locus. All regions of chromosome 9 are represented in abnormal dosage in at least one patient. A 43% increase in AK-1 activity was found to be associated with duplication of the terminal band of the long arm of chromosome 9. Duplication of all other parts of chromosome 9 were associated with normal enzyme activity. These findings not only confirm the assignment of the AK-1 locus to chromosome 9 made previously in somatic cell hybrids, but suggest a more precise assignment to region 9q33 leads to qter. This places the ABO:Np-1:AK-1 linkage group at the distal end of the long arm of chromosome 9."}
{"id": "PMID:184031", "title": "Indophenol-oxidase in patients with Down's syndrome due to simple trisomy and to translocation 21/22.", "content": "The indophenol-oxidase of erythrocytes was studied in three groups (trisomy G 21, unbalanced translocation 21/22, and control group). The increase of IPO activity in patients with trisomy  G 21 was observed, whereas in those with unbalanced translocation 21/22 the levels of IPO were slightly lower than in control group.", "contents": "Indophenol-oxidase in patients with Down's syndrome due to simple trisomy and to translocation 21/22. The indophenol-oxidase of erythrocytes was studied in three groups (trisomy G 21, unbalanced translocation 21/22, and control group). The increase of IPO activity in patients with trisomy  G 21 was observed, whereas in those with unbalanced translocation 21/22 the levels of IPO were slightly lower than in control group."}
{"id": "PMID:184032", "title": "Hormonal studies of uridine utilization in an insect cell line CP-1268 derived from the codling moth Laspeyresia pomonella.", "content": "Ecdysterone decreased cellular growth and the incorporation of uridine into RNA following 4 days of hormone exposure. This hormone did not affect uridine incorporation following short-term exposure up to 25 hours. Juvenile hormone and farnesol both significantly decreased uridine uptake and incorporation into RNA; however, uridine uptake was inhibited to a greater extent than uridine incorporation. Cyclic AMP increased the incorporation of uridine into RNA but had no demonstrable effect on the uptake process. This stimulation was not the result of cAMP degradation products. Cyclic AMP and ecdysterone together produced a significant increase in uridine incorporation into RNA. These studies demonstrate the potential utilization of insect cell lines for studying the mode of action of insect developmental hormones.", "contents": "Hormonal studies of uridine utilization in an insect cell line CP-1268 derived from the codling moth Laspeyresia pomonella. Ecdysterone decreased cellular growth and the incorporation of uridine into RNA following 4 days of hormone exposure. This hormone did not affect uridine incorporation following short-term exposure up to 25 hours. Juvenile hormone and farnesol both significantly decreased uridine uptake and incorporation into RNA; however, uridine uptake was inhibited to a greater extent than uridine incorporation. Cyclic AMP increased the incorporation of uridine into RNA but had no demonstrable effect on the uptake process. This stimulation was not the result of cAMP degradation products. Cyclic AMP and ecdysterone together produced a significant increase in uridine incorporation into RNA. These studies demonstrate the potential utilization of insect cell lines for studying the mode of action of insect developmental hormones."}
{"id": "PMID:184033", "title": "Characterization of a spontaneous undifferentiated carcinoma from an African green monkey (Cercopithecus aethiops).", "content": "An adult male African green monkey (Cercopithecus aethiops) with an undifferentiated carcinoma, probably originating from the nasal mucosa, was received from the Akron, Ohio zoo. Cultivation of this tumor in vitro resulted in a mixture of fibroblastic and epithelial cells which was subsequently separated using differential trypsinization. The neoplastic nature of the cultured epithelial cells was verified by their ability to transplant into athymic nude, or antithymocyte serum-treated mice, where poorly differentiated carcinomas were produced, and cultures of the tumors that arose in nude mice were morphologically similar to pretransplantation cultures. Early cultures showed a normal male karyotype characteristic of the species; however, in long-term cultures, a clearly defined, small submetacentric Y chromosome was not observed. Electron microscopic examination of tumor tissue and cultured tumor cells revealed desmosomes and the presence of cytoplasmic (keratin-type) fibrils, which tended to be organized around the nucleus. In addition to the keratin-type fibrils, the cultured tumor cells also contained a large amount of cytoplasmic inclusion material that may represent keratohyalin granules. There was no evidence of a viral association with tumor material or cultured cells. The cultures were susceptible to infection by vesicular stomatitis virus, Herpesvirus hominis type 1, and H. saimiri, but were resistant to the Epstein-Barr virus.", "contents": "Characterization of a spontaneous undifferentiated carcinoma from an African green monkey (Cercopithecus aethiops). An adult male African green monkey (Cercopithecus aethiops) with an undifferentiated carcinoma, probably originating from the nasal mucosa, was received from the Akron, Ohio zoo. Cultivation of this tumor in vitro resulted in a mixture of fibroblastic and epithelial cells which was subsequently separated using differential trypsinization. The neoplastic nature of the cultured epithelial cells was verified by their ability to transplant into athymic nude, or antithymocyte serum-treated mice, where poorly differentiated carcinomas were produced, and cultures of the tumors that arose in nude mice were morphologically similar to pretransplantation cultures. Early cultures showed a normal male karyotype characteristic of the species; however, in long-term cultures, a clearly defined, small submetacentric Y chromosome was not observed. Electron microscopic examination of tumor tissue and cultured tumor cells revealed desmosomes and the presence of cytoplasmic (keratin-type) fibrils, which tended to be organized around the nucleus. In addition to the keratin-type fibrils, the cultured tumor cells also contained a large amount of cytoplasmic inclusion material that may represent keratohyalin granules. There was no evidence of a viral association with tumor material or cultured cells. The cultures were susceptible to infection by vesicular stomatitis virus, Herpesvirus hominis type 1, and H. saimiri, but were resistant to the Epstein-Barr virus."}
{"id": "PMID:184034", "title": "Control of immune responses by cyclic AMP and lymphocytes that adhere to histamine columns.", "content": "Mixed lymphocytes from human peripheral blood, murine spleens, lymph nodes or thymus glands have pharmacologically specific receptors for histamine, beta mimetic catecholamines and prostaglandins. When these cells are exposed to the panoply of drugs mentioned above, their intracellular cyclic AMP concentrations increase. The biologic consequences of such an increase were at first elusive. Now we know that the immune potential of some murine spleen cells may be modulated and the release of lysosomal enzymes and histamine from human leukocytes may be inhibited. This paper concentrates on the effects that manipulation of cells with amine receptors has on their immune function. Recent studies have revealed that a subpopulation of splenic suppressor T cells responds to increases in its cyclic AMP content by reversing its suppressive effects on the humoral antibody response. When these T cells are removed from the murine cell population by their differential adherence to insolubilized conjugates of histamine with albumin, the remainder of the cells are more responsive to sheep cell antigen, as tested by transferring the spleen cells together with the antigen into lethally irradiated recipient animals. The suppressor T cells that adhere to the insolubilized conjugates of histamine-albumin (called histamine-rabbit serum albumin-Sepharose, or HRS) are Ia positive, they appear to have receptors for histamine, beta adrenergic amines and prostaglandins of the E series, and when stimulated by these agents their in vivo and in vitro suppressor actions are reversed. The reversal seems quantitatively dependent on cyclic AMP accumulation. Receptors for the amines and prostaglandins are found on the T cell precursors of cell mediated immunity. They develop on some T effector cells in selected models of allogeneic target cell lysis. The receptors also appear to develop on selected B cells once these cells become committed to antibody production. The distribution of receptors on all leukocytes has not been adequately studied nor has their full potential in the immune response been studied in detail.", "contents": "Control of immune responses by cyclic AMP and lymphocytes that adhere to histamine columns. Mixed lymphocytes from human peripheral blood, murine spleens, lymph nodes or thymus glands have pharmacologically specific receptors for histamine, beta mimetic catecholamines and prostaglandins. When these cells are exposed to the panoply of drugs mentioned above, their intracellular cyclic AMP concentrations increase. The biologic consequences of such an increase were at first elusive. Now we know that the immune potential of some murine spleen cells may be modulated and the release of lysosomal enzymes and histamine from human leukocytes may be inhibited. This paper concentrates on the effects that manipulation of cells with amine receptors has on their immune function. Recent studies have revealed that a subpopulation of splenic suppressor T cells responds to increases in its cyclic AMP content by reversing its suppressive effects on the humoral antibody response. When these T cells are removed from the murine cell population by their differential adherence to insolubilized conjugates of histamine with albumin, the remainder of the cells are more responsive to sheep cell antigen, as tested by transferring the spleen cells together with the antigen into lethally irradiated recipient animals. The suppressor T cells that adhere to the insolubilized conjugates of histamine-albumin (called histamine-rabbit serum albumin-Sepharose, or HRS) are Ia positive, they appear to have receptors for histamine, beta adrenergic amines and prostaglandins of the E series, and when stimulated by these agents their in vivo and in vitro suppressor actions are reversed. The reversal seems quantitatively dependent on cyclic AMP accumulation. Receptors for the amines and prostaglandins are found on the T cell precursors of cell mediated immunity. They develop on some T effector cells in selected models of allogeneic target cell lysis. The receptors also appear to develop on selected B cells once these cells become committed to antibody production. The distribution of receptors on all leukocytes has not been adequately studied nor has their full potential in the immune response been studied in detail."}
{"id": "PMID:184040", "title": "Cell-mediated immunity to varicella-zoster virus demonstrated by viral inactivation with human leukocytes.", "content": "Cell-mediated immunity to varicella-zoster (V-Z) virus in persons immune to varicella has been demonstrated, using a tissue culture technique. Cell-mediated immunity was reflected by the ability of peripheral leukocytes (lymphocytes and monocytes) from human donors to inactivate V-Z virus. Leukocytes were stimulated by the addition of noninfectious V-Z antigen to cultures newly infected with V-Z virus. Several days leter, the V-Z virus in these cultures was titered. When leukocytes from donors immune to caricella were used, a significant decrease in V-Z titer, compared with controls, was noted. When leukocytes from donors susceptible to varicella were tested, no decrease in V-Z virus titer was found. A mixed population of lymphocytes and monocytes from immune donors was required to demonstrate inactivation of V-Z virus. The development of specific cell-mediated immunity to V-Z virus may play a role in termination of varicella and in prevention of second attacks of this disease.", "contents": "Cell-mediated immunity to varicella-zoster virus demonstrated by viral inactivation with human leukocytes. Cell-mediated immunity to varicella-zoster (V-Z) virus in persons immune to varicella has been demonstrated, using a tissue culture technique. Cell-mediated immunity was reflected by the ability of peripheral leukocytes (lymphocytes and monocytes) from human donors to inactivate V-Z virus. Leukocytes were stimulated by the addition of noninfectious V-Z antigen to cultures newly infected with V-Z virus. Several days leter, the V-Z virus in these cultures was titered. When leukocytes from donors immune to caricella were used, a significant decrease in V-Z titer, compared with controls, was noted. When leukocytes from donors susceptible to varicella were tested, no decrease in V-Z virus titer was found. A mixed population of lymphocytes and monocytes from immune donors was required to demonstrate inactivation of V-Z virus. The development of specific cell-mediated immunity to V-Z virus may play a role in termination of varicella and in prevention of second attacks of this disease."}
{"id": "PMID:184041", "title": "Serological studies with reovirus-like enteritis agent.", "content": "The age distribution of antibody to the human reovirus-like enteritis agent, and to the antigenically related Nebraska calf diarrhea virus (NCDV) was studied in serum specimens obtained from 592 children hospitalized in Boston. Sera were examined for complement-fixation (CF) antibody to the human agent, and for CF and indirect immunofluorescence-staining antibodies to NCDV. The curve of antibody frequency was similar in each of the three assays, showing a steep rise in the 6- to 18-month-old age groups; these results indicate the early acquisition of antibody to the reovirus-like enteritis agent. The majority of children and young adults possessed CF- and immunofluorescence-stainable antibodies. There was a significant association between antibody prevalence data obtained with the human CF antigen and with the two NCDV antigens; this association was closest between the human and NCDV CF antigens.", "contents": "Serological studies with reovirus-like enteritis agent. The age distribution of antibody to the human reovirus-like enteritis agent, and to the antigenically related Nebraska calf diarrhea virus (NCDV) was studied in serum specimens obtained from 592 children hospitalized in Boston. Sera were examined for complement-fixation (CF) antibody to the human agent, and for CF and indirect immunofluorescence-staining antibodies to NCDV. The curve of antibody frequency was similar in each of the three assays, showing a steep rise in the 6- to 18-month-old age groups; these results indicate the early acquisition of antibody to the reovirus-like enteritis agent. The majority of children and young adults possessed CF- and immunofluorescence-stainable antibodies. There was a significant association between antibody prevalence data obtained with the human CF antigen and with the two NCDV antigens; this association was closest between the human and NCDV CF antigens."}
{"id": "PMID:184042", "title": "Cytomegalovirus infection and immunity in renal allograft recipients: assessment of the competence of humoral immunity.", "content": "Cytomegalovirus (CMV) infections are prevalent in renal allograft recipients. The purpose of this ongoing study is to attempt to elucidate the mechanism(s) responsible for the enhanced susceptibility to CMV infections on the part of transplant patients and for their apparent inability to eradicate the infection once it starts. The present report assesses the competence of humoral immunity to CMV in renal allograft recipients. The total study population was comprised of 41 renal allograft recipients (10 followed prospectively) and 38 age-matched control subjects. The overall CMV infection rate in renal allograft recipients was 90.2%, and in 11 cohort control subjects it was 45.5%. Active infection was present in 61.0% of transplant patients (24.0% of these had CMV disease) and in 18.2% of the cohorts. THESE DIFFERENCES ARE SIGNIFICANT. CMV complement fixation and neutralization antibody prevalence was similar in 10 patients with renal failure undergoing hemodialysis before transplantation and in 23 control subjects. There was similarly no difference in antibody response between allograft recipients in whom the infection was primary (eight subjects) or secondary (17 subjects). We conclude that despite immunosuppressant therapy (with azathioprine and corticosteroids), humoral immunity to CMV is not impaired in transplant patients with either a primary or secondary infection.", "contents": "Cytomegalovirus infection and immunity in renal allograft recipients: assessment of the competence of humoral immunity. Cytomegalovirus (CMV) infections are prevalent in renal allograft recipients. The purpose of this ongoing study is to attempt to elucidate the mechanism(s) responsible for the enhanced susceptibility to CMV infections on the part of transplant patients and for their apparent inability to eradicate the infection once it starts. The present report assesses the competence of humoral immunity to CMV in renal allograft recipients. The total study population was comprised of 41 renal allograft recipients (10 followed prospectively) and 38 age-matched control subjects. The overall CMV infection rate in renal allograft recipients was 90.2%, and in 11 cohort control subjects it was 45.5%. Active infection was present in 61.0% of transplant patients (24.0% of these had CMV disease) and in 18.2% of the cohorts. THESE DIFFERENCES ARE SIGNIFICANT. CMV complement fixation and neutralization antibody prevalence was similar in 10 patients with renal failure undergoing hemodialysis before transplantation and in 23 control subjects. There was similarly no difference in antibody response between allograft recipients in whom the infection was primary (eight subjects) or secondary (17 subjects). We conclude that despite immunosuppressant therapy (with azathioprine and corticosteroids), humoral immunity to CMV is not impaired in transplant patients with either a primary or secondary infection."}
{"id": "PMID:184043", "title": "Bacillus pumilus polysaccharide cross-reactive with meningococcal group A polysaccharide.", "content": "A polysaccharide, antigenically and structurally related to meningococcal group A polysaccharide, was isolated from Bacillus pumilus Sh-17. This enteric bacterium has been implicated as a source of natural meningococcal group A immunity (Myerowitz et al., 1973). The B. pumilus polysaccharide was composed of a homopolymer of (1-6)-N-acetyl-manosamine-1-phosphate, glycerol phosphate teichoic acid-containing N-acetylglucosamine and alkali-labile alanine esters, and a mucopeptide. The cross-reaction was due to the poly-(1-6)-N-acetyl-mannosamine-1-phosphate in the B. pumilus and the meningococcal group A polysaccharides, based on the following evidence. Both polysaccharides contained N-acetyl-mannosamine phosphate. Periodate oxidized the mannosamine phosphate residues of the polysaccharide and destroyed their precipitating activity with meningococcal group A antiserum. Mild acid treatment released phosphomonoesters and destroyed the meningococcal group A precipitating activity of both polysaccharides. N-acetyl-mannosamine-6-phosphate inhibited the precipitation reaction between strain Sh-17 and meningococcal group A antisera. Only mannosamine phosphate was detected in trichloroacetic acid extracts of Sh-17 polysaccharide and meningococcal group A antigen-antibody precipitates.", "contents": "Bacillus pumilus polysaccharide cross-reactive with meningococcal group A polysaccharide. A polysaccharide, antigenically and structurally related to meningococcal group A polysaccharide, was isolated from Bacillus pumilus Sh-17. This enteric bacterium has been implicated as a source of natural meningococcal group A immunity (Myerowitz et al., 1973). The B. pumilus polysaccharide was composed of a homopolymer of (1-6)-N-acetyl-manosamine-1-phosphate, glycerol phosphate teichoic acid-containing N-acetylglucosamine and alkali-labile alanine esters, and a mucopeptide. The cross-reaction was due to the poly-(1-6)-N-acetyl-mannosamine-1-phosphate in the B. pumilus and the meningococcal group A polysaccharides, based on the following evidence. Both polysaccharides contained N-acetyl-mannosamine phosphate. Periodate oxidized the mannosamine phosphate residues of the polysaccharide and destroyed their precipitating activity with meningococcal group A antiserum. Mild acid treatment released phosphomonoesters and destroyed the meningococcal group A precipitating activity of both polysaccharides. N-acetyl-mannosamine-6-phosphate inhibited the precipitation reaction between strain Sh-17 and meningococcal group A antisera. Only mannosamine phosphate was detected in trichloroacetic acid extracts of Sh-17 polysaccharide and meningococcal group A antigen-antibody precipitates."}
{"id": "PMID:184044", "title": "Antibodies to BK virus structural and tumor antigens in human sera from normal persons and from patients with various diseases, including neoplasia.", "content": "Sera from 1,279 patients with various diseases were examined for the presence of antibodies to BK virus (BKV) capsid antigens. The percentage of positive sera was comparable in all the diseases except rheumatoid arthritis and chronic nephropathies, where a slightly higher prevalence was found. Sera from 952 patients with tumors were examined for the presence of antibodies to BKV tumor and capsid antigens in comparison with a matched control group of 501 blood donors. Sera from 11 tumor patients (1.15%) and from 4 normal controls (0.80%) had antibodies to BKV tumor antigen. No higher prevalence of antibodies to BKV capsid antigens was found in any cancer type except in carcinomas of the urinary bladder, where the percentage of positive sera and of sera with high titers was higher than in other groups. BKV infection is discussed in relation to its possible connection with human non-neoplastic diseases as well as with human tumors and to its activation under conditions of immunosuppressive therapy.", "contents": "Antibodies to BK virus structural and tumor antigens in human sera from normal persons and from patients with various diseases, including neoplasia. Sera from 1,279 patients with various diseases were examined for the presence of antibodies to BK virus (BKV) capsid antigens. The percentage of positive sera was comparable in all the diseases except rheumatoid arthritis and chronic nephropathies, where a slightly higher prevalence was found. Sera from 952 patients with tumors were examined for the presence of antibodies to BKV tumor and capsid antigens in comparison with a matched control group of 501 blood donors. Sera from 11 tumor patients (1.15%) and from 4 normal controls (0.80%) had antibodies to BKV tumor antigen. No higher prevalence of antibodies to BKV capsid antigens was found in any cancer type except in carcinomas of the urinary bladder, where the percentage of positive sera and of sera with high titers was higher than in other groups. BKV infection is discussed in relation to its possible connection with human non-neoplastic diseases as well as with human tumors and to its activation under conditions of immunosuppressive therapy."}
{"id": "PMID:184045", "title": "Antigenic analysis of isolated polypeptides from Visna virus.", "content": "The antigenic activity of 10 Visna polypeptides separated by gel filtration in the presence of 6 M guanidine hydrochloride (GuHCl) was examined with rabbit antisera made specific for Visna virus. The results showed that the first (GuHCl 1) and the ninth (GuHCl 9) polypeptide peak reacted with the antisera when examined in immunodiffusion, passive hemagglutination, and complement fixation tests. Whole virus, GuHCl 1, and GuHCl 9, when tested with the antisera, appeared to be immunologically identical in the immunodiffusion test. However, GuHCl 1 reacted weakly with the antisera by all three techniques as compared with GuHCl 9 and whole virus. GuHCl 9, when subjected to polyacrylamide gel electrophoresis containing 0.1% sodium lauryl sulfate, revealed the presence of one polypeptide with a molecular weight of 25,000. By the same method, GuHCl 1 was found to contain an aggregate of four different polypeptides, the major one having a molecular weight of 25,000. The results indicate that the antigenic activity of both GuHCl 1 and GuHCl 9 was associated with a single polypeptide having a molecular weight of 25,000.", "contents": "Antigenic analysis of isolated polypeptides from Visna virus. The antigenic activity of 10 Visna polypeptides separated by gel filtration in the presence of 6 M guanidine hydrochloride (GuHCl) was examined with rabbit antisera made specific for Visna virus. The results showed that the first (GuHCl 1) and the ninth (GuHCl 9) polypeptide peak reacted with the antisera when examined in immunodiffusion, passive hemagglutination, and complement fixation tests. Whole virus, GuHCl 1, and GuHCl 9, when tested with the antisera, appeared to be immunologically identical in the immunodiffusion test. However, GuHCl 1 reacted weakly with the antisera by all three techniques as compared with GuHCl 9 and whole virus. GuHCl 9, when subjected to polyacrylamide gel electrophoresis containing 0.1% sodium lauryl sulfate, revealed the presence of one polypeptide with a molecular weight of 25,000. By the same method, GuHCl 1 was found to contain an aggregate of four different polypeptides, the major one having a molecular weight of 25,000. The results indicate that the antigenic activity of both GuHCl 1 and GuHCl 9 was associated with a single polypeptide having a molecular weight of 25,000."}
{"id": "PMID:184046", "title": "In vitro studies on Rickettsia-host cell interactions: lag phase in intracellular growth cycle as a function of stage of growth of infecting Rickettsia prowazeki, with preliminary observations on inhibition of rickettsial uptake by host cell fragments.", "content": "Two Rickettsia prowazeki seeds, an \"early\" seed in the logarithmic or exponential growth phase and a \"late\" seed in the stationary or possibly early decline phase, were prepared in chicken embryo (CE) cell cultures and compared with respect to morphology and infection cycle in CE cells in culture. Differences in size and ultrastructure of the organisms in the two seeds were similar to those seen in other gram-negative bacteria at comparable stages to growth. Vacuolar structures, rare in log-phase organisms, were common in stationary-phase organisms. Minute spherical forms reminiscent of minicells were seen in the stationary-phase preparations. In quantitative uptake experiments, organisms, typical in size and morphology of each preparation, had comparable capacity per plaque-forming unit to penetrate into CE cells in suspension when the seeds had been depleted of host cell membrane fragments and other debris. This suggests that host cell fragments, presumably of membrane origin, competitively inhibit rickettsial uptake by intact CE cells. Organisms of the log-phase organisms displayed a lag phase of about 7.5 h, during which they enlarged and increased in intensity of staining, before entering the log phase of growth.", "contents": "In vitro studies on Rickettsia-host cell interactions: lag phase in intracellular growth cycle as a function of stage of growth of infecting Rickettsia prowazeki, with preliminary observations on inhibition of rickettsial uptake by host cell fragments. Two Rickettsia prowazeki seeds, an \"early\" seed in the logarithmic or exponential growth phase and a \"late\" seed in the stationary or possibly early decline phase, were prepared in chicken embryo (CE) cell cultures and compared with respect to morphology and infection cycle in CE cells in culture. Differences in size and ultrastructure of the organisms in the two seeds were similar to those seen in other gram-negative bacteria at comparable stages to growth. Vacuolar structures, rare in log-phase organisms, were common in stationary-phase organisms. Minute spherical forms reminiscent of minicells were seen in the stationary-phase preparations. In quantitative uptake experiments, organisms, typical in size and morphology of each preparation, had comparable capacity per plaque-forming unit to penetrate into CE cells in suspension when the seeds had been depleted of host cell membrane fragments and other debris. This suggests that host cell fragments, presumably of membrane origin, competitively inhibit rickettsial uptake by intact CE cells. Organisms of the log-phase organisms displayed a lag phase of about 7.5 h, during which they enlarged and increased in intensity of staining, before entering the log phase of growth."}
{"id": "PMID:184047", "title": "Diarrhea in gnotobiotic calves caused by the reovirus-like agent of human infantile gastroenteritis.", "content": "Gnotobiotic newborn calves were found to be susceptible to infection with the reovirus-like agent of human infantile gastroenteritis (HRVL). Infection was based on (i) seroresponse using immunofluorescence and (ii) fecal shedding of virus particles using electron microscopy. Virus was detected in fecal samples for at least 2 to as long as 7 days after inoculation, although peak virus concentrations were observed on days 1 to 4. Diarrheal illness was observed in seven calves on second to fourth serial passage of HRVL in calves but in none of four animals studied on first passage. Diarrhea began 15 to 30.5 h (mean = 22.3 h) post-inoculation and lasted less than 24 h; three of the seven animals that developed diarrhea were also depressed or anorectic.", "contents": "Diarrhea in gnotobiotic calves caused by the reovirus-like agent of human infantile gastroenteritis. Gnotobiotic newborn calves were found to be susceptible to infection with the reovirus-like agent of human infantile gastroenteritis (HRVL). Infection was based on (i) seroresponse using immunofluorescence and (ii) fecal shedding of virus particles using electron microscopy. Virus was detected in fecal samples for at least 2 to as long as 7 days after inoculation, although peak virus concentrations were observed on days 1 to 4. Diarrheal illness was observed in seven calves on second to fourth serial passage of HRVL in calves but in none of four animals studied on first passage. Diarrhea began 15 to 30.5 h (mean = 22.3 h) post-inoculation and lasted less than 24 h; three of the seven animals that developed diarrhea were also depressed or anorectic."}
{"id": "PMID:184048", "title": "Pathogenesis of herpes simplex virus types 1 and 2 in mice after various routes of inoculation.", "content": "The pathogenesis of herpes simplex virus (HSV) types 1 and 2 was compared after inoculation of mice by different routes. Intravaginal inoculation of HSV-1 and HSV-2 produced a local infection, with virus recovery from the vagina through 5 days. Virus was recovered from the spinal cords 4 to 5 days after inoculation but not from liver, kidney, lung, spleen, or blood. Intravenous or intraperitoneal inoculation of HSV-2 produced a focal necrotic hepatitis similar to that described previously (S. C. Mogenson, B. Teisner, and H.K. Andersen, 1974). The viral etiology of the liver lesions was confirmed by virus isolation (through 4 days) and electron microscopy. No evidence of infection of the kidney, lung, blood, or spleen was observed, although virus was isolated from spinal cord homogenates 7 days after inoculation. HSV-1 inoculation by the intraperitoneal or intravenous route resulted in virus isolation from the kidney during the 7-day harvest period, without producing overt pathological changes. Virus was isolated from spinal cord homogenates 2 to 3 days after HSV-1 inoculation but not from homogenates prepared from spleen, lung, or blood. Increases in serum transaminase activity were observed after systemic (intravenous) inoculation of HSV-2 but not after HSV-1 inoculation.", "contents": "Pathogenesis of herpes simplex virus types 1 and 2 in mice after various routes of inoculation. The pathogenesis of herpes simplex virus (HSV) types 1 and 2 was compared after inoculation of mice by different routes. Intravaginal inoculation of HSV-1 and HSV-2 produced a local infection, with virus recovery from the vagina through 5 days. Virus was recovered from the spinal cords 4 to 5 days after inoculation but not from liver, kidney, lung, spleen, or blood. Intravenous or intraperitoneal inoculation of HSV-2 produced a focal necrotic hepatitis similar to that described previously (S. C. Mogenson, B. Teisner, and H.K. Andersen, 1974). The viral etiology of the liver lesions was confirmed by virus isolation (through 4 days) and electron microscopy. No evidence of infection of the kidney, lung, blood, or spleen was observed, although virus was isolated from spinal cord homogenates 7 days after inoculation. HSV-1 inoculation by the intraperitoneal or intravenous route resulted in virus isolation from the kidney during the 7-day harvest period, without producing overt pathological changes. Virus was isolated from spinal cord homogenates 2 to 3 days after HSV-1 inoculation but not from homogenates prepared from spleen, lung, or blood. Increases in serum transaminase activity were observed after systemic (intravenous) inoculation of HSV-2 but not after HSV-1 inoculation."}
{"id": "PMID:184049", "title": "Assay of bovine interferons in cultures of the porcine cell line IB-RS-2.", "content": "An assay for bovine interferons has been developed using the porcine cell line IB-RS-2 and a bovine enterovirus, CBV-D, as challenge virus. The method is based on estimation of cytopathic effect measured by uptake of neutral red. Teh assay is simple, sensitive, and reproducible. A comparative test of different viruses in IB-RS-2 cells and secondary calf kidney cells revealed that the sensitivity of a virus to interferon can vary up to 1,000-fold in the two cell systems. Vesicular stomatitis virus was found to be rather insensitive to interferon in IB-RS-2 cells.", "contents": "Assay of bovine interferons in cultures of the porcine cell line IB-RS-2. An assay for bovine interferons has been developed using the porcine cell line IB-RS-2 and a bovine enterovirus, CBV-D, as challenge virus. The method is based on estimation of cytopathic effect measured by uptake of neutral red. Teh assay is simple, sensitive, and reproducible. A comparative test of different viruses in IB-RS-2 cells and secondary calf kidney cells revealed that the sensitivity of a virus to interferon can vary up to 1,000-fold in the two cell systems. Vesicular stomatitis virus was found to be rather insensitive to interferon in IB-RS-2 cells."}
{"id": "PMID:184050", "title": "Fetal and adult bovine interferon production during bovine viral diarrhea virus infection.", "content": "Levels of interferon in adult bovine serum and in fetal bovine serum and tissues were examined during the course of transplacental bovine viral diarrhea virus infection. The cows produced circulating interferon between 2 and 9 days after viral inoculation, with mean peak levels in the serum on day 4. Interferon could be routinely detected in fetal tissues (e.g., thymus, spleen, and kidney) between days 4 and 21 after viral inoculation of the cows at 149 to 150 days of gestation (mid-second trimester) and in fetal serum from day 13 through day 21. Interferon was also detectable in the serum and tissues of fetuses from dams infected at day 95 of gestation (the beginning of the second trimester). In general, no differences were found between the ability of the adult and fetus to produce interferon. Fetal lamb kidney cells were more sensitive to the antiviral effects of bovine interferon than were fetal bovine kidney cells. The antiviral substance from the fetal and adult animals was characterized as interferon by standard criteria.", "contents": "Fetal and adult bovine interferon production during bovine viral diarrhea virus infection. Levels of interferon in adult bovine serum and in fetal bovine serum and tissues were examined during the course of transplacental bovine viral diarrhea virus infection. The cows produced circulating interferon between 2 and 9 days after viral inoculation, with mean peak levels in the serum on day 4. Interferon could be routinely detected in fetal tissues (e.g., thymus, spleen, and kidney) between days 4 and 21 after viral inoculation of the cows at 149 to 150 days of gestation (mid-second trimester) and in fetal serum from day 13 through day 21. Interferon was also detectable in the serum and tissues of fetuses from dams infected at day 95 of gestation (the beginning of the second trimester). In general, no differences were found between the ability of the adult and fetus to produce interferon. Fetal lamb kidney cells were more sensitive to the antiviral effects of bovine interferon than were fetal bovine kidney cells. The antiviral substance from the fetal and adult animals was characterized as interferon by standard criteria."}
{"id": "PMID:184051", "title": "Improved yields of cell-free varicella-zoster virus.", "content": "Systematic studies on the replication of varicella-zoster virus in infected human fetal diploid lung cells have defined more optimal conditions for infection and harvesting of cultures and have led to the production of cell-free virus preparations with infectivity titers of greater than or equal to 10(6) plaque-forming units per ml. The highest yields of cell-free virus were obtained by (i) sonic treatment of the cellular phase of cultures inoculated with trypsin-dispersed infected cells at ratios of 1 infected cell to 6 to 10 uninfected cells in the monolayer and (ii) harvesting cells after 24 to 36 h of incubation at 36 degrees C. At this time the cultures showed minimal viral cytopathic effect. Spread of infectivity occurred much more rapidly in cultures inoculated with whole infected cells than in those infected with cell-free virus. Complement-fixing antigens with improved titers of greater than or equal to 1:128 were prepared from varicella-zoster virus-infected cell cultures in the same manner as cell-free virus, but harvested after 3 to 4 days of incubation when the cultures showed an advanced cytopathic effect.", "contents": "Improved yields of cell-free varicella-zoster virus. Systematic studies on the replication of varicella-zoster virus in infected human fetal diploid lung cells have defined more optimal conditions for infection and harvesting of cultures and have led to the production of cell-free virus preparations with infectivity titers of greater than or equal to 10(6) plaque-forming units per ml. The highest yields of cell-free virus were obtained by (i) sonic treatment of the cellular phase of cultures inoculated with trypsin-dispersed infected cells at ratios of 1 infected cell to 6 to 10 uninfected cells in the monolayer and (ii) harvesting cells after 24 to 36 h of incubation at 36 degrees C. At this time the cultures showed minimal viral cytopathic effect. Spread of infectivity occurred much more rapidly in cultures inoculated with whole infected cells than in those infected with cell-free virus. Complement-fixing antigens with improved titers of greater than or equal to 1:128 were prepared from varicella-zoster virus-infected cell cultures in the same manner as cell-free virus, but harvested after 3 to 4 days of incubation when the cultures showed an advanced cytopathic effect."}
{"id": "PMID:184052", "title": "Rhesus monkeys kidney cells persistently infected with Simian Virus 40: production of defective interfering virus and acquisition of the transformed phenotype.", "content": "Monolayer cultures of LLC-MK2 rhesus monkey kidney cells became persistently infected with simian virus 40 (SV40) when infected at a multiplicity of infection of 100 plaque-forming units/cell. A stable carrier state developed characterized by extensive viral proliferation without obvious cytopathic effect other than the slow growth of these cultures. By 11 weeks all cells produced the SV40 T antigen. In contrast, less than 5% of the cells produced V antigen. Virus-free clonal isolates were obtained by cloning in SV40 antiserum. Continuous cultivation in antiserum resulted in a temporary cure of unclone cultures. When virus did eventually reappear in the \"cured\" cultures the titers remained low. The virus produced by the carrier culture was defective at both 31 and 37% c, and it interfered with the growth of standard s40 during mixed infection of CV-1 green monkey kidney cells. All of the interfering activity in carrier culture homogenates could be sedimented by centrifugation at 109,000 x g for 3 h. These cultures were completely susceptible to vesicular stomatitis virus. Extensive viral deoxyribonucleic acid synthesis occurred in CV-1 cells infected with carrier culture virus. Carrier culture homogenates are only slightly less cytopathic to CV-1 cells than standard SV40. The carrier culture express several properties of SV40 transformation.", "contents": "Rhesus monkeys kidney cells persistently infected with Simian Virus 40: production of defective interfering virus and acquisition of the transformed phenotype. Monolayer cultures of LLC-MK2 rhesus monkey kidney cells became persistently infected with simian virus 40 (SV40) when infected at a multiplicity of infection of 100 plaque-forming units/cell. A stable carrier state developed characterized by extensive viral proliferation without obvious cytopathic effect other than the slow growth of these cultures. By 11 weeks all cells produced the SV40 T antigen. In contrast, less than 5% of the cells produced V antigen. Virus-free clonal isolates were obtained by cloning in SV40 antiserum. Continuous cultivation in antiserum resulted in a temporary cure of unclone cultures. When virus did eventually reappear in the \"cured\" cultures the titers remained low. The virus produced by the carrier culture was defective at both 31 and 37% c, and it interfered with the growth of standard s40 during mixed infection of CV-1 green monkey kidney cells. All of the interfering activity in carrier culture homogenates could be sedimented by centrifugation at 109,000 x g for 3 h. These cultures were completely susceptible to vesicular stomatitis virus. Extensive viral deoxyribonucleic acid synthesis occurred in CV-1 cells infected with carrier culture virus. Carrier culture homogenates are only slightly less cytopathic to CV-1 cells than standard SV40. The carrier culture express several properties of SV40 transformation."}
{"id": "PMID:184053", "title": "Analysis and modification of opiate reinforcement.", "content": "The authors describe a research protocol for the evaluation of narcotic antagonists which examines the heroin-seeking behavior of hard-core heroin addicts on a research ward under blocked and unblocked conditions. Each patient served as his own control. This paper serves as an introduction to a series of papers which follow dealing with behavioral, psychiatric, and aftercare results. It describes detailed methods and preliminary results for the first 21 subjects admitted to the study. More specific results are reported in the papers that follow.", "contents": "Analysis and modification of opiate reinforcement. The authors describe a research protocol for the evaluation of narcotic antagonists which examines the heroin-seeking behavior of hard-core heroin addicts on a research ward under blocked and unblocked conditions. Each patient served as his own control. This paper serves as an introduction to a series of papers which follow dealing with behavioral, psychiatric, and aftercare results. It describes detailed methods and preliminary results for the first 21 subjects admitted to the study. More specific results are reported in the papers that follow."}
{"id": "PMID:184054", "title": "Opiate antagonists and the modification of heroin self-administration behavior in man: an experimental study.", "content": "The heroin self-administration behavior of 8 inpatient heroin addicts was examined for 10 days under blocked (i.e., following ingestion of narcotic antagonists--naloxone or naltrexone) and unblocked (no antagonist) conditions. In the unblocked state, subjects injected all the available heroin, but they ceased heroin use almost completely following antagonist administration. Possible explanations for these results are discussed along with their implications for treatment.", "contents": "Opiate antagonists and the modification of heroin self-administration behavior in man: an experimental study. The heroin self-administration behavior of 8 inpatient heroin addicts was examined for 10 days under blocked (i.e., following ingestion of narcotic antagonists--naloxone or naltrexone) and unblocked (no antagonist) conditions. In the unblocked state, subjects injected all the available heroin, but they ceased heroin use almost completely following antagonist administration. Possible explanations for these results are discussed along with their implications for treatment."}
{"id": "PMID:184055", "title": "Aftercare on narcotic antagonists: prospects and problems.", "content": "This study examines the problems and prospects of aftercare of the multiple treatment failure opiate addict who is being treated with narcotic antagonists (primarily naltrexone). At the time of this paper, 21 patients had been admitted to the Drug Addiction Research Project at McLean Hospital, with a retention rate of 42%. \"Completers,\" \"noncompleters,\" and \"dropouts\" could not be differentiated on the basis of demographic or psychiatric variables, thus making it impossible to define the population most suited for antagonist treatment. The degree of carry-over into the first month in the community, for those who successfully completed the inpatient segment of the program, disappeared over time. The nonreinforcing (lack of euphoric effect) properties of the antagonists and the resultant high level of motivation necessary for the continuation of its use by the patient make this form of treatment suitable for only a small percentage of the \"hard core\" addict population.", "contents": "Aftercare on narcotic antagonists: prospects and problems. This study examines the problems and prospects of aftercare of the multiple treatment failure opiate addict who is being treated with narcotic antagonists (primarily naltrexone). At the time of this paper, 21 patients had been admitted to the Drug Addiction Research Project at McLean Hospital, with a retention rate of 42%. \"Completers,\" \"noncompleters,\" and \"dropouts\" could not be differentiated on the basis of demographic or psychiatric variables, thus making it impossible to define the population most suited for antagonist treatment. The degree of carry-over into the first month in the community, for those who successfully completed the inpatient segment of the program, disappeared over time. The nonreinforcing (lack of euphoric effect) properties of the antagonists and the resultant high level of motivation necessary for the continuation of its use by the patient make this form of treatment suitable for only a small percentage of the \"hard core\" addict population."}
{"id": "PMID:184058", "title": "Free radicals in pyrimidines: 5-thymyl radical nitrogen splitting in irradiated thymidine.", "content": "Single crystals of thymidine irradiated with 4.0 MeV electrons exhibit the well-known eight-line e.s.r. spectrum due to the 5-thymyl radical. A careful analysis of these lines revealed an extra hyperfine splitting, which by a combination of INDO-MO calculations and experiments, was attributed to an interaction between the unpaired electron and the N3-H group.", "contents": "Free radicals in pyrimidines: 5-thymyl radical nitrogen splitting in irradiated thymidine. Single crystals of thymidine irradiated with 4.0 MeV electrons exhibit the well-known eight-line e.s.r. spectrum due to the 5-thymyl radical. A careful analysis of these lines revealed an extra hyperfine splitting, which by a combination of INDO-MO calculations and experiments, was attributed to an interaction between the unpaired electron and the N3-H group."}
{"id": "PMID:184060", "title": "Cytomegalovirus hepatitis in an artificial kidney unit.", "content": "Serum hepatitis is a dreaded risk in connection with regular dialysis treatment (RDT). Liver damage, however, can be cuased by other diseases, such as infection with cytomegalovirus (CMV). Two cases in our artificial kidney unit revealed signs of liver damage with increased liver enzyme activity. Case 1, a woman, was on RDT after an unsuccessful renal transplantation, and Case 2, a man, belonged to the staff. Serum hepatitis was initially suspected in both cases, but repeated examinations of the sera revealed no hepatitis B antigen or antibodies (HbAg and HbAb). Later on, both showed a significant increase in antibodies  in complement fixations reaction (CF) to CMV-antigen. CMV could be isolated from urine in Case 2. Case 1 had been bilaterally nephrectomized. The symptoms (tiredness, muscle pain and headache) and the course of the disease were mild in both cases and liver enzymes became normal within 1-2 weeks. Twenty out of 31 examined patients and staff had antibodies in CF to CMV-antigen, but in none was there any significant increase. The source of infection may have been transfusion of fresh blood in Case 1, but in Case 2 no particular source could be suspected. Thus, in liver damage CMV-infection may be an etiological alternative. In routine work at artficial kidney unite patients and personnel are regularly examined in respect of bilirubin, liver enzymes, HbAg and HbAb in serum. We recommend also examination of serum for antibodies in CF to CMV-antigen. Until a firm differential diagnosis has been established the patient should be isolated and the dialysis equipments used only by that patient.", "contents": "Cytomegalovirus hepatitis in an artificial kidney unit. Serum hepatitis is a dreaded risk in connection with regular dialysis treatment (RDT). Liver damage, however, can be cuased by other diseases, such as infection with cytomegalovirus (CMV). Two cases in our artificial kidney unit revealed signs of liver damage with increased liver enzyme activity. Case 1, a woman, was on RDT after an unsuccessful renal transplantation, and Case 2, a man, belonged to the staff. Serum hepatitis was initially suspected in both cases, but repeated examinations of the sera revealed no hepatitis B antigen or antibodies (HbAg and HbAb). Later on, both showed a significant increase in antibodies  in complement fixations reaction (CF) to CMV-antigen. CMV could be isolated from urine in Case 2. Case 1 had been bilaterally nephrectomized. The symptoms (tiredness, muscle pain and headache) and the course of the disease were mild in both cases and liver enzymes became normal within 1-2 weeks. Twenty out of 31 examined patients and staff had antibodies in CF to CMV-antigen, but in none was there any significant increase. The source of infection may have been transfusion of fresh blood in Case 1, but in Case 2 no particular source could be suspected. Thus, in liver damage CMV-infection may be an etiological alternative. In routine work at artficial kidney unite patients and personnel are regularly examined in respect of bilirubin, liver enzymes, HbAg and HbAb in serum. We recommend also examination of serum for antibodies in CF to CMV-antigen. Until a firm differential diagnosis has been established the patient should be isolated and the dialysis equipments used only by that patient."}
{"id": "PMID:184062", "title": "Ultrastructural cytology of prostate carcinoma cells from Wistar rats.", "content": "Cells from spontaneous adenocarcinomas of the prostate (Pollard, M.: J. Natl. Cancer Inst. 51: 1235, 1973) in aged Lobund Wistar rats were examined by electron microscopy. Cytologic structures of the rat prostate tumor cells resembled analogous structures from human prostate tumor cells. These findings support the prospect that the rat prostate tumor will provide a model system of prostate cancer in man.", "contents": "Ultrastructural cytology of prostate carcinoma cells from Wistar rats. Cells from spontaneous adenocarcinomas of the prostate (Pollard, M.: J. Natl. Cancer Inst. 51: 1235, 1973) in aged Lobund Wistar rats were examined by electron microscopy. Cytologic structures of the rat prostate tumor cells resembled analogous structures from human prostate tumor cells. These findings support the prospect that the rat prostate tumor will provide a model system of prostate cancer in man."}
{"id": "PMID:184067", "title": "[Virology of acute upper respiratory tract infections (author's transl)].", "content": "The virology of acute upper respiratory tract infections is presented in a survey. The first part includes general properties of viruses (structure, replication, maturation, classification), aetiological and immunological problems of viral infections. The different respiratory viruses and their clinical picture in particular are summarized in the second part.", "contents": "[Virology of acute upper respiratory tract infections (author's transl)]. The virology of acute upper respiratory tract infections is presented in a survey. The first part includes general properties of viruses (structure, replication, maturation, classification), aetiological and immunological problems of viral infections. The different respiratory viruses and their clinical picture in particular are summarized in the second part."}
{"id": "PMID:184063", "title": "The new program of the World Health Organization in medical virology.", "content": "The World Health Organization (WHO) convened a Scientific Group to adapt its program in virus diseases to recent progress in virology. The program consists of (a) general activities, such as reference services and the supplying of reagents by the WHO Collaborating Centres and (b) specific activities to solve problems-including the promotion of necessary research-caused by certain diseases of public health importance. The Group reviewed problems caused by influenza and other respiratory viruses, enteroviruses, gastroenteritis viruses (for which types A and B have been proposed as a convenient nomenclature), viral hepatitis, viruses in water and sewage, arboviruses, arenaviruses and Marburg virus, measles and rubella vaccination, smallpox, rabies, chronic infections, herpesviruses, oncogenic viruses, congenital infections, nosocomial infections, chlamydial and rickettsial infections, and mycoplasma infections.", "contents": "The new program of the World Health Organization in medical virology. The World Health Organization (WHO) convened a Scientific Group to adapt its program in virus diseases to recent progress in virology. The program consists of (a) general activities, such as reference services and the supplying of reagents by the WHO Collaborating Centres and (b) specific activities to solve problems-including the promotion of necessary research-caused by certain diseases of public health importance. The Group reviewed problems caused by influenza and other respiratory viruses, enteroviruses, gastroenteritis viruses (for which types A and B have been proposed as a convenient nomenclature), viral hepatitis, viruses in water and sewage, arboviruses, arenaviruses and Marburg virus, measles and rubella vaccination, smallpox, rabies, chronic infections, herpesviruses, oncogenic viruses, congenital infections, nosocomial infections, chlamydial and rickettsial infections, and mycoplasma infections."}
{"id": "PMID:184064", "title": "Characterization of single-cell clonal lines derived from HSV-2-transformed mouse cells.", "content": "A BALB/c continuous cell line, 238, was transformed following infection with UV-inactivated herpes simplex virus type 2 (HSV-2) was designated H238. Several cell lines were derived from single cells of H238 by cloning in soft agar. The clonal lines express cytoplasmic antigens by immunofluorescence when reacted with rabbit HSV-2 antiserum and mouse tumor-bearer serum. The cloned cell lines induce tumors in immunocompetent mice by the subcutaneous route with a 100% incidence at an inoculum of 10(6) cells. These properties are consistent with those of the H238 parent cell line. In contrast to the parent line, however, the cloned cell lines do not elicit HSV neutralizing antibody in the tumor-bearing host.", "contents": "Characterization of single-cell clonal lines derived from HSV-2-transformed mouse cells. A BALB/c continuous cell line, 238, was transformed following infection with UV-inactivated herpes simplex virus type 2 (HSV-2) was designated H238. Several cell lines were derived from single cells of H238 by cloning in soft agar. The clonal lines express cytoplasmic antigens by immunofluorescence when reacted with rabbit HSV-2 antiserum and mouse tumor-bearer serum. The cloned cell lines induce tumors in immunocompetent mice by the subcutaneous route with a 100% incidence at an inoculum of 10(6) cells. These properties are consistent with those of the H238 parent cell line. In contrast to the parent line, however, the cloned cell lines do not elicit HSV neutralizing antibody in the tumor-bearing host."}
{"id": "PMID:184074", "title": "Infiltrative corneal lesions resembling fibrous histiocytoma: clinical and pathologic findings in six dogs and one cat.", "content": "Infiltrating corneal lesions developed in 6 dogs and 1 cat. In each case, the site of origin appeared to be the corneal limbus. The lesions were characterized by continuous growth, a benign appearance, and a tendency to recur following excision keratoplasty. Each lesion was of a proliferative, inflammatory nature, histologically resembling fibrous histiocytoma. Of the 6 dogs in the series, 4 were Collies.", "contents": "Infiltrative corneal lesions resembling fibrous histiocytoma: clinical and pathologic findings in six dogs and one cat. Infiltrating corneal lesions developed in 6 dogs and 1 cat. In each case, the site of origin appeared to be the corneal limbus. The lesions were characterized by continuous growth, a benign appearance, and a tendency to recur following excision keratoplasty. Each lesion was of a proliferative, inflammatory nature, histologically resembling fibrous histiocytoma. Of the 6 dogs in the series, 4 were Collies."}
{"id": "PMID:184075", "title": "Test method for determination of virucidal efficacy of liquid surface disinfectants.", "content": "A test method was developed incorporating AOAC use-dilution stainless steel Penicylinders and H.Ep.-2 tissue culture cells for the evaluation of disinfectants as virucides. The subsequent collaborative study using Herpes simplex and poliovirus type 1 in evaluation against a quaternary ammonium compound, phenolic, and iodiphor disinfectants indicated that the basic test procedure is sound. However, an improved virus concentration technique and a modified method for drying virus-contaminated cylinders are recommended. In addition, other types of disinfectants and test viruses should be included in order to demonstrate that the procedure is versatile as well as reproducible.", "contents": "Test method for determination of virucidal efficacy of liquid surface disinfectants. A test method was developed incorporating AOAC use-dilution stainless steel Penicylinders and H.Ep.-2 tissue culture cells for the evaluation of disinfectants as virucides. The subsequent collaborative study using Herpes simplex and poliovirus type 1 in evaluation against a quaternary ammonium compound, phenolic, and iodiphor disinfectants indicated that the basic test procedure is sound. However, an improved virus concentration technique and a modified method for drying virus-contaminated cylinders are recommended. In addition, other types of disinfectants and test viruses should be included in order to demonstrate that the procedure is versatile as well as reproducible."}
{"id": "PMID:184076", "title": "Silicic acid chromatographic separation of polychlorinated biphenyls and pesticides: some contaminants and limitations.", "content": "The Armour and Burke method for separating polychlorinated biphenyls (PCBs) from pesticides involves the use of silicic acid. However, we detected di-2-ethylhexyl phthalate, PCBs, and other impurities as interfering contaminants in several batches of silicic acid. The presence of H2SO4 in some batches of silicic acid is inferred. The acid may be responsible for the production of contaminants which interfere in gas-liquid chromatographic analyses. Contaminants in silicic acid are reduced by extracting the adsorbent with solvent, and/or partitioning the concentrated pesticide fraction with 1N NaOH. These purification procedures provide separations relatively free of impurities, but result in reduced adsorbent activity. PCB-pesticide separations are reproducible only within a given batch lot of silicic acid because of the varying adsorbent characteristics of each lot. Alternative adsorbents should be explored for most PCB-pesticide separations.", "contents": "Silicic acid chromatographic separation of polychlorinated biphenyls and pesticides: some contaminants and limitations. The Armour and Burke method for separating polychlorinated biphenyls (PCBs) from pesticides involves the use of silicic acid. However, we detected di-2-ethylhexyl phthalate, PCBs, and other impurities as interfering contaminants in several batches of silicic acid. The presence of H2SO4 in some batches of silicic acid is inferred. The acid may be responsible for the production of contaminants which interfere in gas-liquid chromatographic analyses. Contaminants in silicic acid are reduced by extracting the adsorbent with solvent, and/or partitioning the concentrated pesticide fraction with 1N NaOH. These purification procedures provide separations relatively free of impurities, but result in reduced adsorbent activity. PCB-pesticide separations are reproducible only within a given batch lot of silicic acid because of the varying adsorbent characteristics of each lot. Alternative adsorbents should be explored for most PCB-pesticide separations."}
{"id": "PMID:184077", "title": "High-pressure liquid chromatography of benzo(a) pyrene and benzo (ghi) perylene in oil-contaminated shellfish.", "content": "A high-pressure liquid chromatographic procedure is described for the determination of benzo(a) pyrene and benzo(ghi) perylene. These polynuclear aromatics are extracted with acetonitrile and partitioned into petroleum ether, the petroleum ether is removed, and the residue is saponified. The compounds are purified and isolated by passing the residue through a silica gel column and a high-pressure liquid chromatographic column, and detected by their ultraviolet absorption. Recoveries of standards through the procedure averaged 104%.", "contents": "High-pressure liquid chromatography of benzo(a) pyrene and benzo (ghi) perylene in oil-contaminated shellfish. A high-pressure liquid chromatographic procedure is described for the determination of benzo(a) pyrene and benzo(ghi) perylene. These polynuclear aromatics are extracted with acetonitrile and partitioned into petroleum ether, the petroleum ether is removed, and the residue is saponified. The compounds are purified and isolated by passing the residue through a silica gel column and a high-pressure liquid chromatographic column, and detected by their ultraviolet absorption. Recoveries of standards through the procedure averaged 104%."}
{"id": "PMID:184078", "title": "Ca2+-induced conformational changes of spin-labeled g2 chain bound to myosin and the effect of phosphorylation.", "content": "One of the low molecular weight components of myosin, g2, was isolated by alkali treatment of myosin and was chemically modified with a spin label reagent, 4-maleimido-2,2,6,6-tetramethylpiperidinooxyl. The label on g2 showed a rather weakly immobilized ESR spectrum and it was clearly affected by Ca2+; the half-maximal change was at around pCa 4. The spin-labeled g2 was incorporated into myosin by exchange with the intrinsic g2 of myosin in 0.6 M KSCN or 4 M LiC1. The label on g2 became strongly immobilized on association with myosin. Under the conditions used, ESR spectral change due to Ca2+ occurred at two different concentration ranges, which were as low as pCa 8 and at around pCa 4. Phosphorylated g2 was isolated from myosin after the protein kinase [EC 2.1.1.37]-catalyzed phosphorylation of myosin and it was also modified with the maleimide label. Dephosphorylation of the phosphorylated g2 was performed using E. coli alkaline phosphatase [EC 3.1.3.1]. The effects of Ca2+ on the ESR spectra of phosphorylated and dephosphorylated g2 were investigated on the state associated with myosin. A change in the ESR spectrum from strongly immobilized to weakly immobilized states was observed with both g2 chains on the addition of Ca2+. However, the effective concentration  ranges of Ca2+ were quite different; around pCa 4 for the phosphorylated g2 and around pCa 8 for the dephosphorylated g2. The results indicate that g2 undergoes a conformational change at physiological levels of Ca2+ sufficient to saturate troponin, but it does not do so after phosphorylation.", "contents": "Ca2+-induced conformational changes of spin-labeled g2 chain bound to myosin and the effect of phosphorylation. One of the low molecular weight components of myosin, g2, was isolated by alkali treatment of myosin and was chemically modified with a spin label reagent, 4-maleimido-2,2,6,6-tetramethylpiperidinooxyl. The label on g2 showed a rather weakly immobilized ESR spectrum and it was clearly affected by Ca2+; the half-maximal change was at around pCa 4. The spin-labeled g2 was incorporated into myosin by exchange with the intrinsic g2 of myosin in 0.6 M KSCN or 4 M LiC1. The label on g2 became strongly immobilized on association with myosin. Under the conditions used, ESR spectral change due to Ca2+ occurred at two different concentration ranges, which were as low as pCa 8 and at around pCa 4. Phosphorylated g2 was isolated from myosin after the protein kinase [EC 2.1.1.37]-catalyzed phosphorylation of myosin and it was also modified with the maleimide label. Dephosphorylation of the phosphorylated g2 was performed using E. coli alkaline phosphatase [EC 3.1.3.1]. The effects of Ca2+ on the ESR spectra of phosphorylated and dephosphorylated g2 were investigated on the state associated with myosin. A change in the ESR spectrum from strongly immobilized to weakly immobilized states was observed with both g2 chains on the addition of Ca2+. However, the effective concentration  ranges of Ca2+ were quite different; around pCa 4 for the phosphorylated g2 and around pCa 8 for the dephosphorylated g2. The results indicate that g2 undergoes a conformational change at physiological levels of Ca2+ sufficient to saturate troponin, but it does not do so after phosphorylation."}
{"id": "PMID:184079", "title": "In vitro polymerization of flagellar and ciliary outer fiber tubulin into microtubules.", "content": "About 10--20% of the total protein in the outer fiber fraction was solubilized by sonication in a solution containing 5 mM MES, 0.5 mM MgSO4, 1.0 mM EGTA, 1.0 mM GTP, and 0 or 50 mM KC1 at pH 6.7. The sonicated extract was shown by analytical centrifugation to consist largely of a 6 S component (tubulin dimer), having a molecular weight of 103,000, as determined by gel filtration, and possessing a colchicine-binding activity of 0.8 mole per tubulin dimer. The tubulin fraction failed to polymerize into microtubules by itself. Addition of a small amount of the ciliary outer fiber fragments or reconstituted short brain microtubules, however, induced polymerization, as demonstrated by viscosity of flow birefringence changes as well as light or electron microscopic observations. The growth of heterogeneous microtubules upon mixing outer fiber tubulin with DEAE-dextran-decorated brain microtubules was observed by electron microscopy. Microtubules were reconstituted from outer fiber tubulin without addition of any nuclei fraction when a concentrated tubulin fraction was warmed at 35degree. A few doublet-like microtubules or pairs of parallel singlet microtubules that were closely aligned longitudinally could be observed among many singlet microtubules. Unlike other fiber microtubules, the reconstituted polymers were depolymerized by exposure to Ca2+ ions, high or low ionic strength, colchicine, low temperature or SH reagents. No microtubules were assembled under these conditions.", "contents": "In vitro polymerization of flagellar and ciliary outer fiber tubulin into microtubules. About 10--20% of the total protein in the outer fiber fraction was solubilized by sonication in a solution containing 5 mM MES, 0.5 mM MgSO4, 1.0 mM EGTA, 1.0 mM GTP, and 0 or 50 mM KC1 at pH 6.7. The sonicated extract was shown by analytical centrifugation to consist largely of a 6 S component (tubulin dimer), having a molecular weight of 103,000, as determined by gel filtration, and possessing a colchicine-binding activity of 0.8 mole per tubulin dimer. The tubulin fraction failed to polymerize into microtubules by itself. Addition of a small amount of the ciliary outer fiber fragments or reconstituted short brain microtubules, however, induced polymerization, as demonstrated by viscosity of flow birefringence changes as well as light or electron microscopic observations. The growth of heterogeneous microtubules upon mixing outer fiber tubulin with DEAE-dextran-decorated brain microtubules was observed by electron microscopy. Microtubules were reconstituted from outer fiber tubulin without addition of any nuclei fraction when a concentrated tubulin fraction was warmed at 35degree. A few doublet-like microtubules or pairs of parallel singlet microtubules that were closely aligned longitudinally could be observed among many singlet microtubules. Unlike other fiber microtubules, the reconstituted polymers were depolymerized by exposure to Ca2+ ions, high or low ionic strength, colchicine, low temperature or SH reagents. No microtubules were assembled under these conditions."}
{"id": "PMID:184080", "title": "Synthesis of various phosphodiesters and phosphomonoesters with ribonuclease N.", "content": "1. 3'-Guanylyl-ethanol, 3'-guanylyl-propanol, and 3'-guanylyl-alpha-glycerol were synthesized by ribonuclease N1 [EC 3.1.4.8] using guanosine 2',3'-cyclic phosphate as a phosphate donor and various alcohols as phosphate acceptors. The yields of these phosphodiesters were 15%, 13.5%, 38.2%, respectively, with respect to phosphate donor under the optimum conditions. No phosphodiester was synthesized when 2-propanol was used as a phosphate acceptor. Thus, primary alcoholic hydroxyl groups may be regarded as the preferred phosphate acceptor. 2. 3'-Guanylyl-glucose and 3'-guanylyl-ribose were synthesized using glucose and ribose as phosphate acceptors. Under the optimum conditions, the yields of guanylyl-glucose amounted to 52.0%, while that of guanylyl-ribose was much lower. The guanylyl-glucose can be regarded as 3'-guanylyl-6-glucopyranose, based on the results of periodate oxidation. 3. Neither hydroxyamino acids (serine and threonine) nor N-acetylserinamide could be phosphorylated under the conditions used for the above phosphorylations. 4. 3'-Guanylyl-glycerol obtained as above was hydrolyzed by snake venon phosphodiesterase to produce glycerol 3-phosphate. The latter consisted of L-glycerol 3-phosphate (ca 17%) and the D-isomer (ca. 83%). Ribonuclease N1 thus catalyzes an asymmetric synthesis.", "contents": "Synthesis of various phosphodiesters and phosphomonoesters with ribonuclease N. 1. 3'-Guanylyl-ethanol, 3'-guanylyl-propanol, and 3'-guanylyl-alpha-glycerol were synthesized by ribonuclease N1 [EC 3.1.4.8] using guanosine 2',3'-cyclic phosphate as a phosphate donor and various alcohols as phosphate acceptors. The yields of these phosphodiesters were 15%, 13.5%, 38.2%, respectively, with respect to phosphate donor under the optimum conditions. No phosphodiester was synthesized when 2-propanol was used as a phosphate acceptor. Thus, primary alcoholic hydroxyl groups may be regarded as the preferred phosphate acceptor. 2. 3'-Guanylyl-glucose and 3'-guanylyl-ribose were synthesized using glucose and ribose as phosphate acceptors. Under the optimum conditions, the yields of guanylyl-glucose amounted to 52.0%, while that of guanylyl-ribose was much lower. The guanylyl-glucose can be regarded as 3'-guanylyl-6-glucopyranose, based on the results of periodate oxidation. 3. Neither hydroxyamino acids (serine and threonine) nor N-acetylserinamide could be phosphorylated under the conditions used for the above phosphorylations. 4. 3'-Guanylyl-glycerol obtained as above was hydrolyzed by snake venon phosphodiesterase to produce glycerol 3-phosphate. The latter consisted of L-glycerol 3-phosphate (ca 17%) and the D-isomer (ca. 83%). Ribonuclease N1 thus catalyzes an asymmetric synthesis."}
{"id": "PMID:184081", "title": "Physical and chemical studies on bacterial superoxide dismutases. Purification and some anion binding properties of the iron-containing protein of Escherichia coli B.", "content": "Highly purified iron superoxide dismutase was obtained from Escherichia coli B using a modification of the procedure of Yost and Jridovich (Yost, F. J., Jr., and Fridovich, I. (1973) J. Biol. Chem. 248, 4905-4908). The protein contained 1.8 +/- 0.2 atoms of iron per 38,700 g of protein. We have found that cyanide does not bind to the Fe3+ ion of iron dismutase but fluoride and azide have moderately large binding constants. Optical and electron paramagnetic resonance (EPR) measurements suggested that 2 fluoride ions could associate with each iron atom with the first having an association constant of approximately 520 M-1 and the second with an estimated value of 24 M-1. Activity measurements yielded an inhibition constant for fluoride of 30 M-1. At room temperature only one azide binds to the Fe3+ (K = 760 M-1) and this does not interfere with superoxide dismutase activity. Upon freezing solutions of iron superoxide dismutase in the presence of excess azide their color changes from yellow to pink. Combined EPR and optical titrations with azide suggest the presence of two binding sites on Fe3+ with only the first being occupied at room temperature and the second binding azide only upon freezing the solution. The results suggest that each Fe3+ ion of this superoxide dismutase has two coordination positions available for interaction with solute molecules but only one is necessary for catalysis of the superoxide dismutation reaction. The EPR, optical, and circular dichroism spectra of the native protein and the various fluoride and azide complexes are presented.", "contents": "Physical and chemical studies on bacterial superoxide dismutases. Purification and some anion binding properties of the iron-containing protein of Escherichia coli B. Highly purified iron superoxide dismutase was obtained from Escherichia coli B using a modification of the procedure of Yost and Jridovich (Yost, F. J., Jr., and Fridovich, I. (1973) J. Biol. Chem. 248, 4905-4908). The protein contained 1.8 +/- 0.2 atoms of iron per 38,700 g of protein. We have found that cyanide does not bind to the Fe3+ ion of iron dismutase but fluoride and azide have moderately large binding constants. Optical and electron paramagnetic resonance (EPR) measurements suggested that 2 fluoride ions could associate with each iron atom with the first having an association constant of approximately 520 M-1 and the second with an estimated value of 24 M-1. Activity measurements yielded an inhibition constant for fluoride of 30 M-1. At room temperature only one azide binds to the Fe3+ (K = 760 M-1) and this does not interfere with superoxide dismutase activity. Upon freezing solutions of iron superoxide dismutase in the presence of excess azide their color changes from yellow to pink. Combined EPR and optical titrations with azide suggest the presence of two binding sites on Fe3+ with only the first being occupied at room temperature and the second binding azide only upon freezing the solution. The results suggest that each Fe3+ ion of this superoxide dismutase has two coordination positions available for interaction with solute molecules but only one is necessary for catalysis of the superoxide dismutation reaction. The EPR, optical, and circular dichroism spectra of the native protein and the various fluoride and azide complexes are presented."}
{"id": "PMID:184082", "title": "Studies on the effects of coenzyme A-SH: acetyl coenzyme A, nicotinamide adenine dinucleotide: reduced nicotinamide adenine dinucleotide, and adenosine diphosphate: adenosine triphosphate ratios on the interconversion of active and inactive pyruvate dehydrogenase in isolated rat heart mitochondria.", "content": "The content of coenzyme A-SH (CoASH) and acetyl-CoA of suspensions of rat heart mitochondria was stabilized by the addition of DL-carnitine and acetyl-DL-carnitine, in the presence of the respiratory inhibitor rotenone. The mitochondrial content of NAD+ and NADH was similarly stabilized by the addition of acetoacetate and DL-3-hydroxybutyrate, and the content of ADP and ATP was imposed by the addition of these nucleotides to the mitochondrial suspension, in the presence of uncoupling agent and oligomycin, to inhibit ATPase. Under these conditions, mitochondrial CoASH/acetyl-CoA, NAD+/ NADH, and ADP/ATP ratios could be varied independently, and the effect on the interconversion of active and inactive pyruvate dehydrogenase could be studied. Decreases in both CoASH/acetyl-CoA and NAD+/NADH ratios were shown to be inhibitory to the steady state activity of pyruvate dehydrogenase, and this effect is described at three different ADP/ATP ratios and different concentrations of added MgCl2. A new steady state level of activity was achieved within 10 min of a change in either CoASH/acetyl-CoA or NAD+/NADH ratio; the rate of inactivation was much higher than the rate of reactivation under these conditions. Effects of CoASH/acetyl-CoA and NAD+/NADH may be additive but are still quantitatively lesser than the changes in activity of pyruvate dehydrogenase induced by changes in ADP/ATP ratio. The variation in activity of pyruvate dehydrogenase with ADP/ATP ratio is described in the absence of changes in the other two ratios, conditions which were not met in earlier studies which employed the oxidation of different substrates to generate changes in all three ratios.", "contents": "Studies on the effects of coenzyme A-SH: acetyl coenzyme A, nicotinamide adenine dinucleotide: reduced nicotinamide adenine dinucleotide, and adenosine diphosphate: adenosine triphosphate ratios on the interconversion of active and inactive pyruvate dehydrogenase in isolated rat heart mitochondria. The content of coenzyme A-SH (CoASH) and acetyl-CoA of suspensions of rat heart mitochondria was stabilized by the addition of DL-carnitine and acetyl-DL-carnitine, in the presence of the respiratory inhibitor rotenone. The mitochondrial content of NAD+ and NADH was similarly stabilized by the addition of acetoacetate and DL-3-hydroxybutyrate, and the content of ADP and ATP was imposed by the addition of these nucleotides to the mitochondrial suspension, in the presence of uncoupling agent and oligomycin, to inhibit ATPase. Under these conditions, mitochondrial CoASH/acetyl-CoA, NAD+/ NADH, and ADP/ATP ratios could be varied independently, and the effect on the interconversion of active and inactive pyruvate dehydrogenase could be studied. Decreases in both CoASH/acetyl-CoA and NAD+/NADH ratios were shown to be inhibitory to the steady state activity of pyruvate dehydrogenase, and this effect is described at three different ADP/ATP ratios and different concentrations of added MgCl2. A new steady state level of activity was achieved within 10 min of a change in either CoASH/acetyl-CoA or NAD+/NADH ratio; the rate of inactivation was much higher than the rate of reactivation under these conditions. Effects of CoASH/acetyl-CoA and NAD+/NADH may be additive but are still quantitatively lesser than the changes in activity of pyruvate dehydrogenase induced by changes in ADP/ATP ratio. The variation in activity of pyruvate dehydrogenase with ADP/ATP ratio is described in the absence of changes in the other two ratios, conditions which were not met in earlier studies which employed the oxidation of different substrates to generate changes in all three ratios."}
{"id": "PMID:184083", "title": "Regulation of carbohydrate permeases and adenylate cyclase in Escherichia coli. Studies with mutant strains in which enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system is thermolabile.", "content": "Carbohydrate uptake and cyclic adenosine 3':5'-monophosphate (cyclic AMP) synthesis were studied employing mutant strains of Escherichia coli in which Enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system was heat-labile. Partial loss of Enzyme I activity, which resulted from incubation of cells at the nonpermissive temperature, depressed the rate and extent of methyl alpha-glucoside uptake. Temperature inactivation of Enzyme I also rendered cyclic AMP synthesis and the uptake of several carbohydrates (glycerol, maltose, melibiose, and lactose) hypersensitive to inhibition by methyl alpha-glucoside. Protein synthesis did not appear to be required for these effects. The parental strains and \"revertant\" strains in which Enzyme I was less sensitive to temperature did not exhibit heat-enhanced regulation. Inhibition was abolished by the crr mutation. The results suggest that Enzyme I functions as a catalytic component of the regulatory system. Simple positive selection procedures are described for the isolation of bacterial mutants which are deficient for either Enzyme I or the heat-stable protein of the phosphotransferase system.", "contents": "Regulation of carbohydrate permeases and adenylate cyclase in Escherichia coli. Studies with mutant strains in which enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system is thermolabile. Carbohydrate uptake and cyclic adenosine 3':5'-monophosphate (cyclic AMP) synthesis were studied employing mutant strains of Escherichia coli in which Enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system was heat-labile. Partial loss of Enzyme I activity, which resulted from incubation of cells at the nonpermissive temperature, depressed the rate and extent of methyl alpha-glucoside uptake. Temperature inactivation of Enzyme I also rendered cyclic AMP synthesis and the uptake of several carbohydrates (glycerol, maltose, melibiose, and lactose) hypersensitive to inhibition by methyl alpha-glucoside. Protein synthesis did not appear to be required for these effects. The parental strains and \"revertant\" strains in which Enzyme I was less sensitive to temperature did not exhibit heat-enhanced regulation. Inhibition was abolished by the crr mutation. The results suggest that Enzyme I functions as a catalytic component of the regulatory system. Simple positive selection procedures are described for the isolation of bacterial mutants which are deficient for either Enzyme I or the heat-stable protein of the phosphotransferase system."}
{"id": "PMID:184084", "title": "Binding of progesterone receptor by nuclear preparations of rabbit and guinea pig uterus.", "content": "Guinea pig and rabbit uterine nuclei bound [3H] progesterone in vitro only in the presence of cytosol from estrogen-stimulated uteri. Nuclei from unstimulated and estrogen-stimulated uteri bound progesterone equally well. Nuclei of nontarget tissues also bound progesterone, but to a lesser extent. The rate of nuclear bindins increased with temperature from 0-30 degrees. At 25 degrees nuclear binding remained stable for at least 3 h, but at temperatures of 30 degrees and greater, nuclear binding decreased rapidly after 15 min. Activation of the progesterone-cytoplasmic receptor complex (the change in the complex that enables it to bind quickly to nuclei at 0 degrees) took place slowly at temperatures from 0-5 degrees and rapidly at 10-25 degrees. Activation was facilitated by dilution of the cytosol. Some activation occurred in diluted cytosol in the absence of added progesterone. The cytoplasmic progesterone receptor had a sedimentation coefficient of 7 S when concentrated cytosol (20 mg of protein/ml) was incubated with progesterone at 0 degrees in 5 mM phosphate buffer. Diluting the cytosol and increasing the temperature to 20 degrees caused the sedimentation coefficient to decrease to 5.5 S. Gel filtration of guinea pig uterine cytosol on Sephadex G-100, in the absence of progesterone, yielded a progesterone-binding fraction in the void volume, with a sedimentation coefficient of 5.5 S. The complex of progesterone with the material in the void volume was taken up by nuclei at 0 degrees more rapidly than the complex of progesterone and crude cytosol. The nuclear uptake of progesterone was decreased in phosphate buffer of concentrations greater than 80 mM. Under conditions that favor the nuclear binding of progesterone, the sedimentation coefficient of the cytoplasmic progesterone receptor was 5.5 S. This may be the form of the preceptor which is taken up by nuclei. In decreasing order of effectiveness, unlabeled progesterone, 5 alpha-pregnane-3,20-dione, corticosterone 20 alpha-hydroxy-4-pregnen-3-one, testosterone, estradiol-17 beta, and cortisol competed with [3H] progesterone for binding to nuclei.", "contents": "Binding of progesterone receptor by nuclear preparations of rabbit and guinea pig uterus. Guinea pig and rabbit uterine nuclei bound [3H] progesterone in vitro only in the presence of cytosol from estrogen-stimulated uteri. Nuclei from unstimulated and estrogen-stimulated uteri bound progesterone equally well. Nuclei of nontarget tissues also bound progesterone, but to a lesser extent. The rate of nuclear bindins increased with temperature from 0-30 degrees. At 25 degrees nuclear binding remained stable for at least 3 h, but at temperatures of 30 degrees and greater, nuclear binding decreased rapidly after 15 min. Activation of the progesterone-cytoplasmic receptor complex (the change in the complex that enables it to bind quickly to nuclei at 0 degrees) took place slowly at temperatures from 0-5 degrees and rapidly at 10-25 degrees. Activation was facilitated by dilution of the cytosol. Some activation occurred in diluted cytosol in the absence of added progesterone. The cytoplasmic progesterone receptor had a sedimentation coefficient of 7 S when concentrated cytosol (20 mg of protein/ml) was incubated with progesterone at 0 degrees in 5 mM phosphate buffer. Diluting the cytosol and increasing the temperature to 20 degrees caused the sedimentation coefficient to decrease to 5.5 S. Gel filtration of guinea pig uterine cytosol on Sephadex G-100, in the absence of progesterone, yielded a progesterone-binding fraction in the void volume, with a sedimentation coefficient of 5.5 S. The complex of progesterone with the material in the void volume was taken up by nuclei at 0 degrees more rapidly than the complex of progesterone and crude cytosol. The nuclear uptake of progesterone was decreased in phosphate buffer of concentrations greater than 80 mM. Under conditions that favor the nuclear binding of progesterone, the sedimentation coefficient of the cytoplasmic progesterone receptor was 5.5 S. This may be the form of the preceptor which is taken up by nuclei. In decreasing order of effectiveness, unlabeled progesterone, 5 alpha-pregnane-3,20-dione, corticosterone 20 alpha-hydroxy-4-pregnen-3-one, testosterone, estradiol-17 beta, and cortisol competed with [3H] progesterone for binding to nuclei."}
{"id": "PMID:184085", "title": "Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate.", "content": "Androgen receptors in crude and partially purified 105,000 X g supernatant fractions from rat testis, epididymis, and prostate were studied in vitro using a charcoal adsorption assay and sucrose gradient centrifugation. Androgen metabolism was eliminated during receptor purification allowing determination of the kinetics of [3H]-androgen-receptor complex formation. In all three tissues, receptors were found to have essentially identical capabilities to bind androgen, with the affinity for [3H] dihydrotestosterone being somewhat higher than for [3H] testosterone. Equilibrium dissociation constants for [3H] dihydrotestosterone and [3H] testosterone (KD = 2 to 5 X 10(-10) M) were estimated from independently determined rates of association (ka congruent to 6 X 10(7) M-1 h-1 for [3H] dihydrotestosterone and 2 X 10(8) M-1 h-1 for [3H] testosterone) and dissociation (t 1/2 congruent to 40 hr for [3H] dihydrotestosterone and 15 h [3H] testosterone). Evaluation of the effect of temperature on androgen receptor binding of [3H]testosterone allowed estimation of several thermodynamic parameters, including activation energies of association and dissociation (delta H congruent to 14 kcal/mol), the apparent free energy (delta G congruent to -12 kcal/mol), enthalpy (delta H congruent to -2.5 kcal/mol), and entropy (delta S congruent to 35 cal col-1 K-1). Optimum receptor binding occurred at a pH of 8. Receptor stability was greatly enhanced when bound with androgen. Receptor specificity for testosterone and dihydrotestosterone was demonstrated by competitive binding assays. The potent synthetic androgen, 7 alpha, 17 alpha-dimethyl-19-nortestosterone, inhibited binding of [3H] testosterone or [3H] dihydrotesterone nearly as well as testosterone and dihydrotestosterone while larger amounts of 5 alpha-androstane-3alpha, 17 beta-diol and nonandrogenic steroids were required. Sedimentation coefficients of androgen receptors in all unfractionated supernatants were 4 and 5 to 8 S. Differences in sedimentation coefficients were observed following (NH4)2SO4 precipitation which did not influence the binding properties of the receptors. These results, together with measurements of3alpha/beta-hydroxysteroid oxidoreductase activity in vitro, suggest that organ differences in receptor binding of [3H] dihydrotestosterone and [3H] testosterone in vivo result from relative differences in intracellular concentrations of these androgens rather than from differences in receptor affinities.", "contents": "Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate. Androgen receptors in crude and partially purified 105,000 X g supernatant fractions from rat testis, epididymis, and prostate were studied in vitro using a charcoal adsorption assay and sucrose gradient centrifugation. Androgen metabolism was eliminated during receptor purification allowing determination of the kinetics of [3H]-androgen-receptor complex formation. In all three tissues, receptors were found to have essentially identical capabilities to bind androgen, with the affinity for [3H] dihydrotestosterone being somewhat higher than for [3H] testosterone. Equilibrium dissociation constants for [3H] dihydrotestosterone and [3H] testosterone (KD = 2 to 5 X 10(-10) M) were estimated from independently determined rates of association (ka congruent to 6 X 10(7) M-1 h-1 for [3H] dihydrotestosterone and 2 X 10(8) M-1 h-1 for [3H] testosterone) and dissociation (t 1/2 congruent to 40 hr for [3H] dihydrotestosterone and 15 h [3H] testosterone). Evaluation of the effect of temperature on androgen receptor binding of [3H]testosterone allowed estimation of several thermodynamic parameters, including activation energies of association and dissociation (delta H congruent to 14 kcal/mol), the apparent free energy (delta G congruent to -12 kcal/mol), enthalpy (delta H congruent to -2.5 kcal/mol), and entropy (delta S congruent to 35 cal col-1 K-1). Optimum receptor binding occurred at a pH of 8. Receptor stability was greatly enhanced when bound with androgen. Receptor specificity for testosterone and dihydrotestosterone was demonstrated by competitive binding assays. The potent synthetic androgen, 7 alpha, 17 alpha-dimethyl-19-nortestosterone, inhibited binding of [3H] testosterone or [3H] dihydrotesterone nearly as well as testosterone and dihydrotestosterone while larger amounts of 5 alpha-androstane-3alpha, 17 beta-diol and nonandrogenic steroids were required. Sedimentation coefficients of androgen receptors in all unfractionated supernatants were 4 and 5 to 8 S. Differences in sedimentation coefficients were observed following (NH4)2SO4 precipitation which did not influence the binding properties of the receptors. These results, together with measurements of3alpha/beta-hydroxysteroid oxidoreductase activity in vitro, suggest that organ differences in receptor binding of [3H] dihydrotestosterone and [3H] testosterone in vivo result from relative differences in intracellular concentrations of these androgens rather than from differences in receptor affinities."}
{"id": "PMID:184086", "title": "Cyclid 3':5'-nucleotide phosphodiesterase. Interconvertible multiple forms and their effects on enzyme activity and kinetics.", "content": "An extract of rat liver or human platelet displayed three cyclic 3':5'-nucleotide phosphodiesterase activity peaks (I, II, and III) in a continuous sucrose density gradient when assayed with millimolar adenosine 3':5'-monophosphate (cAMP) or guanosine 3':5'-monophosphate (cGMP). The three fractions obtained from each nucleotide were not superimposable. The molecular weights corresponding to the three activity peaks of cAMP phosphodiesterase in rat liver were approximately: I, 22,000; II, 75,000; and III, 140,000. In both tissues, fraction I was barely detectable when assayed with micromolar concentrations of either nucleotide, presumably because fraction I has low affinity for cAMP and cGMP. Any one of the three forms upon recentrifugation on the gradient generated the others, indicating that they were interconvertible. The multiple forms appear to represent different aggregated states of the enzyme. The ratio of the three forms of cAMP phosphodiesterase in the platelet was shifted by dibutyryl cAMP (B2cAMP) and by the enzyme concentration. B2cAMP enhanced the formation of fraction I. Low enzyme concentration favored the equilibrium towards fraction I, while high enzyme concentration favored fraction III. When phosphodiesterase activities in the extract of rat liver, human platelets, or bovine brain were examined as a function of enzyme concentration, rectilinear rates were observed with micromolar, but not with millimolar cAMP or cGMP. The specific activity with millimolar cAMP was higher with low than with high protein concentrations, suggesting that the dissociated form catalyzed the hydrolysis of cAMP faster than that of the associated form. In contrast, the specific activity with millimolar cGMP was lower with low than with high protein concentrations. Supplementing the reaction mixture with bovine serum albumin to a final constant protein concentration did not affect the activity, suggesting that the concentration of the enzyme rather than that of extraneous proteins affected the enzyme activity. A change in enzyme concentration affected the kinetic properties of phosphodiesterase. A low enzyme concentration of cAMP phosphodiesterase yielded a linear Lineweaver-Burk plot, and a Km of 1.2 X 10(-4) M (bovine), 3 X 10(-5) M (platelet), or 5 X 10(-4) M (liver), while a high enzyme concentration yielded a nonlinear plot, and apparent Km values of 1.4 X 10(-4) M and 2 X 10(-5) M (brain), 4 X 10(-5) M and 3 X 10(-6) M (platelet), or 4 X 10(-5) M and 3 X 10(-6) (liver). Since a low enzyme concentration favored fraction I, the dissociated form, whereas a high enzyme concentration favored fraction III, the associated form, these kinetic constants suggest that the dissociated form exhibits a high Km and the associated form exhibits a low Km. In contrast, a high enzyme concentration gave a linear kinetic plot for cGMP phosphodiesterase, while a low enzyme concentration gave a nonlinear plot...", "contents": "Cyclid 3':5'-nucleotide phosphodiesterase. Interconvertible multiple forms and their effects on enzyme activity and kinetics. An extract of rat liver or human platelet displayed three cyclic 3':5'-nucleotide phosphodiesterase activity peaks (I, II, and III) in a continuous sucrose density gradient when assayed with millimolar adenosine 3':5'-monophosphate (cAMP) or guanosine 3':5'-monophosphate (cGMP). The three fractions obtained from each nucleotide were not superimposable. The molecular weights corresponding to the three activity peaks of cAMP phosphodiesterase in rat liver were approximately: I, 22,000; II, 75,000; and III, 140,000. In both tissues, fraction I was barely detectable when assayed with micromolar concentrations of either nucleotide, presumably because fraction I has low affinity for cAMP and cGMP. Any one of the three forms upon recentrifugation on the gradient generated the others, indicating that they were interconvertible. The multiple forms appear to represent different aggregated states of the enzyme. The ratio of the three forms of cAMP phosphodiesterase in the platelet was shifted by dibutyryl cAMP (B2cAMP) and by the enzyme concentration. B2cAMP enhanced the formation of fraction I. Low enzyme concentration favored the equilibrium towards fraction I, while high enzyme concentration favored fraction III. When phosphodiesterase activities in the extract of rat liver, human platelets, or bovine brain were examined as a function of enzyme concentration, rectilinear rates were observed with micromolar, but not with millimolar cAMP or cGMP. The specific activity with millimolar cAMP was higher with low than with high protein concentrations, suggesting that the dissociated form catalyzed the hydrolysis of cAMP faster than that of the associated form. In contrast, the specific activity with millimolar cGMP was lower with low than with high protein concentrations. Supplementing the reaction mixture with bovine serum albumin to a final constant protein concentration did not affect the activity, suggesting that the concentration of the enzyme rather than that of extraneous proteins affected the enzyme activity. A change in enzyme concentration affected the kinetic properties of phosphodiesterase. A low enzyme concentration of cAMP phosphodiesterase yielded a linear Lineweaver-Burk plot, and a Km of 1.2 X 10(-4) M (bovine), 3 X 10(-5) M (platelet), or 5 X 10(-4) M (liver), while a high enzyme concentration yielded a nonlinear plot, and apparent Km values of 1.4 X 10(-4) M and 2 X 10(-5) M (brain), 4 X 10(-5) M and 3 X 10(-6) M (platelet), or 4 X 10(-5) M and 3 X 10(-6) (liver). Since a low enzyme concentration favored fraction I, the dissociated form, whereas a high enzyme concentration favored fraction III, the associated form, these kinetic constants suggest that the dissociated form exhibits a high Km and the associated form exhibits a low Km. In contrast, a high enzyme concentration gave a linear kinetic plot for cGMP phosphodiesterase, while a low enzyme concentration gave a nonlinear plot..."}
{"id": "PMID:184087", "title": "Conformational stability of the polypeptide components of human high density serum lipoprotein.", "content": "An investigation of the denaturation of the major polypeptides from human serum high density lipoprotein by guanidine hydrochloride reveals that the lipid-free, water-soluble states are minimally stable relative to the random coil states. These findings are in direct contrast to the resistance of intrinsic membrane proteins (in the absence of ligand) to complete unfolding by the same denaturant. Consideration of the denaturation data for the apolipoproteins together with previously published data from this laboratory on ligand-induced conformational changes indicate that these polypeptides possess several similar conformational states which are readily interconvertible.", "contents": "Conformational stability of the polypeptide components of human high density serum lipoprotein. An investigation of the denaturation of the major polypeptides from human serum high density lipoprotein by guanidine hydrochloride reveals that the lipid-free, water-soluble states are minimally stable relative to the random coil states. These findings are in direct contrast to the resistance of intrinsic membrane proteins (in the absence of ligand) to complete unfolding by the same denaturant. Consideration of the denaturation data for the apolipoproteins together with previously published data from this laboratory on ligand-induced conformational changes indicate that these polypeptides possess several similar conformational states which are readily interconvertible."}
{"id": "PMID:184088", "title": "Amino acid transport in isolated rat thymocytes. Effects of divalent cations and ethanol.", "content": "In dispersed rat thymocytes neither basal alpha-aminoisobutyric acid influx nor influx stimulated by insulin, prostaglandin theophylline, or butyryl adenosine 3':5'-monophosphate (cyclic AMP) depended on extracellular calcium or magnesium. The divalent cation ionophore A23187 inhibited both basal and stimulated alpha-aminoisobutyric acid influx. The extent to which influx was inhibited depended on ionophore concentration, extracellular calcium concentration, and time but did not depend on extracellular magnesium. Significant inhibition could be detected at an ionophore concentration of 1 muM and maximal inhibition occurred with 6 muM A23187. A23187 increased cellular uptake of calcium and there was good agred calcium uptake and that for ionophore inhibition of alpha-aminoisobutyric acid influx. Incubating cells with A23187 and then adding ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N',-tetraacetic acid completely reversed ionophore-stimulated cellular calcum uptake but did not reverse inhibition of alpha-aminoisobutyric acid influx. Thus, A23187 produces irreversible inhibition of alpha-aminoisobutyric acid transport in dispersed rat thymocytes. Ethanol abolished insulin-stimulated alpha-aminoisobutyric acid influx but did not alter basal influx or that stimulated by prostaglandin E1, theophylline, or N6,O2'-dibutyryl adenosine 3':5'-monophosphate. Inhibition could be detected with 0.2% (v/v) ethanol and insulin-stimulated alpha-aminoisobutyric influx was abolished with 1% ethanol. The effect of ethanol occurred immediately and could be reversed completely. This ability of ethanol to inhibit selectively insulin-stimulated alpha-aminoisobutyric acid influx indicates that the mechanism through which insulin stimulates alpha-aminoisobutyric acid influx is functionally distinct from the stimulation produced by cyclic AMP.", "contents": "Amino acid transport in isolated rat thymocytes. Effects of divalent cations and ethanol. In dispersed rat thymocytes neither basal alpha-aminoisobutyric acid influx nor influx stimulated by insulin, prostaglandin theophylline, or butyryl adenosine 3':5'-monophosphate (cyclic AMP) depended on extracellular calcium or magnesium. The divalent cation ionophore A23187 inhibited both basal and stimulated alpha-aminoisobutyric acid influx. The extent to which influx was inhibited depended on ionophore concentration, extracellular calcium concentration, and time but did not depend on extracellular magnesium. Significant inhibition could be detected at an ionophore concentration of 1 muM and maximal inhibition occurred with 6 muM A23187. A23187 increased cellular uptake of calcium and there was good agred calcium uptake and that for ionophore inhibition of alpha-aminoisobutyric acid influx. Incubating cells with A23187 and then adding ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N',-tetraacetic acid completely reversed ionophore-stimulated cellular calcum uptake but did not reverse inhibition of alpha-aminoisobutyric acid influx. Thus, A23187 produces irreversible inhibition of alpha-aminoisobutyric acid transport in dispersed rat thymocytes. Ethanol abolished insulin-stimulated alpha-aminoisobutyric acid influx but did not alter basal influx or that stimulated by prostaglandin E1, theophylline, or N6,O2'-dibutyryl adenosine 3':5'-monophosphate. Inhibition could be detected with 0.2% (v/v) ethanol and insulin-stimulated alpha-aminoisobutyric influx was abolished with 1% ethanol. The effect of ethanol occurred immediately and could be reversed completely. This ability of ethanol to inhibit selectively insulin-stimulated alpha-aminoisobutyric acid influx indicates that the mechanism through which insulin stimulates alpha-aminoisobutyric acid influx is functionally distinct from the stimulation produced by cyclic AMP."}
{"id": "PMID:184089", "title": "Hormone secretion and glucose metabolism in islets of Langerhans of the isolated perfused pancreas from normal and streptozotocin diabetic rats.", "content": "The glucose responsiveness of alpha- and beta-cells of normal as well as untreated and insulin-treated streptozotocin diabetic rats was tested in the extracorporeal perfusion system. Also assessed was the possible in vitro effect of added insulin on the glucose sensitivity of islets from untreated diabetic animals. Insulin and glucose responsiveness of the two cell types. The rate of glucose entry islet tissue was estimated, and the effect of glucose on the tissue supply of ATP and lactate and the cyclic 3':5'-AMP level of islets was measured under the above in vitro conditions. It was demonstrated that beta-cells are more accessible to glucose than alpha-cells, that glucose entry into islet cells is not significantly modified by insulin and that glucose had no effect on ATP, lactate and cyclic 3':5'-AMP levels of islet tissue under any of the conditions investigated. High insulin in vitro elevated ATP levels of alpha-cell islets independent of extracellular glucose. Glucose caused insulin release from normal but not from diabetic islets and rapidly and efficiently suppressed stimulated glucagon secretion of the pancreas from normal and insulin treated diabetic rats. Glucose was less effective in inhibiting stimulated glucagon secretion by the pancreas from untreated diabetic rats whether insulin was added to the perfusion media or not. Therefore, profound differences of glucose responsiveness of alpha-cells fail to manifest themselves in alterations of basic parameters of glucose and energy metabolism in contrast to what had been postulated in the literature. It is however, apparent that the glucose responsiveness of alpha-cells is modified by insuling by an as yet undefined mechanism.", "contents": "Hormone secretion and glucose metabolism in islets of Langerhans of the isolated perfused pancreas from normal and streptozotocin diabetic rats. The glucose responsiveness of alpha- and beta-cells of normal as well as untreated and insulin-treated streptozotocin diabetic rats was tested in the extracorporeal perfusion system. Also assessed was the possible in vitro effect of added insulin on the glucose sensitivity of islets from untreated diabetic animals. Insulin and glucose responsiveness of the two cell types. The rate of glucose entry islet tissue was estimated, and the effect of glucose on the tissue supply of ATP and lactate and the cyclic 3':5'-AMP level of islets was measured under the above in vitro conditions. It was demonstrated that beta-cells are more accessible to glucose than alpha-cells, that glucose entry into islet cells is not significantly modified by insulin and that glucose had no effect on ATP, lactate and cyclic 3':5'-AMP levels of islet tissue under any of the conditions investigated. High insulin in vitro elevated ATP levels of alpha-cell islets independent of extracellular glucose. Glucose caused insulin release from normal but not from diabetic islets and rapidly and efficiently suppressed stimulated glucagon secretion of the pancreas from normal and insulin treated diabetic rats. Glucose was less effective in inhibiting stimulated glucagon secretion by the pancreas from untreated diabetic rats whether insulin was added to the perfusion media or not. Therefore, profound differences of glucose responsiveness of alpha-cells fail to manifest themselves in alterations of basic parameters of glucose and energy metabolism in contrast to what had been postulated in the literature. It is however, apparent that the glucose responsiveness of alpha-cells is modified by insuling by an as yet undefined mechanism."}
{"id": "PMID:184090", "title": "Purification and characterization of adrenal cortex mitochondrial cytochrome P-450 specific for cholesterol side chain cleavage activity.", "content": "Cytochrome P-450 was purified from bovine adrenal cortex mitochondria by affinity chromatography using an octylamine-substituted Sepharose column. The resulting optically clear preparation was stable at -20 degrees for months. The specific concentration of cytochrome P-450 in the preparation was about 5 nmol of heme per mg of protein. The preparations were free of adrenodoxin, adrenodoxin reductase, phospholipids, and other heme contaminations. Polyacrylamide gel electrophoresis of the purified cytochrome P-450 preparation treated with sodium dodecyl sulfate and mercaptoethanol showed a single major band with a molecular weight of about 60,000. The optical absorption spectra of the preparation exhibited Soret maxima at 416, 416, and 448 nm for the Fe3+, Fe2+ and the C.Fe2+ complex, respectively. The EPR spectrum showed the characteristic features of the low spin form of ferric cytochrome P-450 with principal components 1.914, 2.241, and 2.415 of the g-tensor. The circular dichroism spectrum revealed two large negative ellipticities at 412 and 350 nm. Fluorescence spectra showed an excitation maximum at 285 nm and an emission maximum at 305 nm with a shoulder at 330 nm as the cytochrome P-450 molecule is excited at 285 nm, or an emission maximum at 335 nm when the cytochrome molecule is excited at 305 nm. After reconstitution with adrenodoxin and its reductase, this cytochrome P-450 was highly active for cholesterol desmolase with an NADPH-generating system as electron donor but was not active for steroid 11beta-hydroxylase.", "contents": "Purification and characterization of adrenal cortex mitochondrial cytochrome P-450 specific for cholesterol side chain cleavage activity. Cytochrome P-450 was purified from bovine adrenal cortex mitochondria by affinity chromatography using an octylamine-substituted Sepharose column. The resulting optically clear preparation was stable at -20 degrees for months. The specific concentration of cytochrome P-450 in the preparation was about 5 nmol of heme per mg of protein. The preparations were free of adrenodoxin, adrenodoxin reductase, phospholipids, and other heme contaminations. Polyacrylamide gel electrophoresis of the purified cytochrome P-450 preparation treated with sodium dodecyl sulfate and mercaptoethanol showed a single major band with a molecular weight of about 60,000. The optical absorption spectra of the preparation exhibited Soret maxima at 416, 416, and 448 nm for the Fe3+, Fe2+ and the C.Fe2+ complex, respectively. The EPR spectrum showed the characteristic features of the low spin form of ferric cytochrome P-450 with principal components 1.914, 2.241, and 2.415 of the g-tensor. The circular dichroism spectrum revealed two large negative ellipticities at 412 and 350 nm. Fluorescence spectra showed an excitation maximum at 285 nm and an emission maximum at 305 nm with a shoulder at 330 nm as the cytochrome P-450 molecule is excited at 285 nm, or an emission maximum at 335 nm when the cytochrome molecule is excited at 305 nm. After reconstitution with adrenodoxin and its reductase, this cytochrome P-450 was highly active for cholesterol desmolase with an NADPH-generating system as electron donor but was not active for steroid 11beta-hydroxylase."}
{"id": "PMID:184091", "title": "Biochemical aspects of cardiac muscle differentiation. Possible control of deoxyribonucleic acid synthesis and cell differentiation by adrenergic innervation and cyclic adenosine 3':5'-monophosphate.", "content": "A single injection of either isoproternol or N6, O2'-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) results in an inhibition in the rate of [3H]thymidine incorporation into DNA of differentiating cardiac muscle of the neonatal rat. This inhibition is not due to substantially altered cellular uptake or catabolism of [3H]thymidine. Inhibition of [3H]thymidine incorporation by isoproterenol or dibutyryl cyclic AMP is potentiated by theophylline. Maximal inhibition (95%) is observed 24 h after administration of isoproterenol, and the rate of incorporation returns to a value 80% of control by 72 h. Norepinephrine also inhibits [3H]thymidine incorporation whereas cyclic GMP, N2, 02-Dibutyryl guanosine 3':5'-monophosphate (dibutyryl cyclic GMP), and phenylephrine have little effect. Equilibrium sedimentation analysis of cardiac muscle DNA in neutral and alkaline cesium chloride gradients using bromodeoxyuridine as a density label indicate that isoproterenol and dibutyryl cyclic AMP inhibit [3H]thymidine incorporation into DNA that is replicating semiconservatively. Administration of isoproterenol or dibutyryl cyclic AMP to neonatal rats inhibits by approximately 60% the incorporation of [3H]thymidine into DNA of tissue slices of cardiac muscle prepared 16 h later. [3H]Thymidine incorporation into DNA of tissue slices is into chains that were growing in vivo. This incorporation is linear for at least 4 h of incubation and is inhibited by isoproterenol and dibutyryl cyclic AMP. Inhibition is not due to altered cellular uptake of [3H]thymidine nor is it due to a cytotoxic action. Several other compounds which elevate intracellular levels of cyclic AMP (epinephrine, norepinephrine, glucagon, and prostaglandin E1) also inhibit [3H]thymidine incorporation into DNA or cardiac muscle tissue slices. Cyclic GMP, dibutyryl cyclic GMP, sodium butyrate, and phenylephrine have little effect. Isoproterenol administered together with theophylline to neonatal rats signficantly stimulates the in corporation of [3H]phenylalanine into total cardiac muscle protein and into myosin. This enhanced incorporation may be due in part to an increase in the cellular uptake of [3H]phenylalanine. DNA synthesis  decreases progressively in differentiating cardiac muscle of the rat during postnatal development and essentially ceases by the middle of the third week (Claycomb, W. C. (1975) J. Biol. Chem. 250, 3229-3235). In reviewing the literature it was found that this decline in synthetic activity correlates temporally with a progressive increase in tissue concentrations of norepinephrine and cyclic AMP and with the anatomical and physiological development of the adrenergic nerves in this tissue. Because of these facts and data presented in this report it is proposed that cell proliferation and cell differentiation in cardiac muscle may be controlled by adrenergic innervation with norepinephrine and cyclic AMP serving as chemical mediators.", "contents": "Biochemical aspects of cardiac muscle differentiation. Possible control of deoxyribonucleic acid synthesis and cell differentiation by adrenergic innervation and cyclic adenosine 3':5'-monophosphate. A single injection of either isoproternol or N6, O2'-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) results in an inhibition in the rate of [3H]thymidine incorporation into DNA of differentiating cardiac muscle of the neonatal rat. This inhibition is not due to substantially altered cellular uptake or catabolism of [3H]thymidine. Inhibition of [3H]thymidine incorporation by isoproterenol or dibutyryl cyclic AMP is potentiated by theophylline. Maximal inhibition (95%) is observed 24 h after administration of isoproterenol, and the rate of incorporation returns to a value 80% of control by 72 h. Norepinephrine also inhibits [3H]thymidine incorporation whereas cyclic GMP, N2, 02-Dibutyryl guanosine 3':5'-monophosphate (dibutyryl cyclic GMP), and phenylephrine have little effect. Equilibrium sedimentation analysis of cardiac muscle DNA in neutral and alkaline cesium chloride gradients using bromodeoxyuridine as a density label indicate that isoproterenol and dibutyryl cyclic AMP inhibit [3H]thymidine incorporation into DNA that is replicating semiconservatively. Administration of isoproterenol or dibutyryl cyclic AMP to neonatal rats inhibits by approximately 60% the incorporation of [3H]thymidine into DNA of tissue slices of cardiac muscle prepared 16 h later. [3H]Thymidine incorporation into DNA of tissue slices is into chains that were growing in vivo. This incorporation is linear for at least 4 h of incubation and is inhibited by isoproterenol and dibutyryl cyclic AMP. Inhibition is not due to altered cellular uptake of [3H]thymidine nor is it due to a cytotoxic action. Several other compounds which elevate intracellular levels of cyclic AMP (epinephrine, norepinephrine, glucagon, and prostaglandin E1) also inhibit [3H]thymidine incorporation into DNA or cardiac muscle tissue slices. Cyclic GMP, dibutyryl cyclic GMP, sodium butyrate, and phenylephrine have little effect. Isoproterenol administered together with theophylline to neonatal rats signficantly stimulates the in corporation of [3H]phenylalanine into total cardiac muscle protein and into myosin. This enhanced incorporation may be due in part to an increase in the cellular uptake of [3H]phenylalanine. DNA synthesis  decreases progressively in differentiating cardiac muscle of the rat during postnatal development and essentially ceases by the middle of the third week (Claycomb, W. C. (1975) J. Biol. Chem. 250, 3229-3235). In reviewing the literature it was found that this decline in synthetic activity correlates temporally with a progressive increase in tissue concentrations of norepinephrine and cyclic AMP and with the anatomical and physiological development of the adrenergic nerves in this tissue. Because of these facts and data presented in this report it is proposed that cell proliferation and cell differentiation in cardiac muscle may be controlled by adrenergic innervation with norepinephrine and cyclic AMP serving as chemical mediators."}
{"id": "PMID:184092", "title": "Leghemoglobin. An electron paramagnetic resonance and optical spectral study of the free protein and its complexes with nicotinate and acetate.", "content": "Electron paramagnetic resonance (EPR) and optical spectra are used as probes of the heme and its ligands in ferric and ferrous leghemoglobin. The proximal ligand to the heme iron atom of ferric soybean leghemoglobin is identified as imidazole by comparison of the EPR of leghemoglobin hydroxide, azide, and cyanide with the corresponding derivatives of human hemoglobin. Optical spectra show that ferric soybean leghemoglobin near room temperature is almost entirely in the high spin state. At 77 K the optical spectrum is that of a low spin compound, while at 1.6 K the EPR is that of a low spin form resembling bis-imidazole heme. Acetate binds to ferric leghemoglobin to form a high spin complex as judged from the optical spectrum. The EPR of this complex is that of high spin ferric heme in a nearly axial environment. The complexes of ferrous leghemoglobin with substituted pyridines exhibit optical absorption maxima near 685 nm, whose absorption maxima and extinctions are strongly dependent on the nature of the substitutents of the pyridine ring; electron withdrawing groups on the pyridine ring shift the absorption maxima to lower energy. A crystal field analysis of the EPR of nicotinate derivatives of ferric leghemoblobin demonstrates that the pyridine nitrogen is also bound to the heme iron in the ferric state. These findings lead us to picture leghemoglobin as a somewhat flexible molecule in which the transition region between the E and F helices may act as a hinge, opening a small amount at higher temperature to a stable configuration in which the protein is high spin and can accommodate exogenous ligand molecules and closing at low temperature to a second stable configuration in which the protein is low spin and in which close approach of the E helix permits the distal histidine to become the principal sixth ligand.", "contents": "Leghemoglobin. An electron paramagnetic resonance and optical spectral study of the free protein and its complexes with nicotinate and acetate. Electron paramagnetic resonance (EPR) and optical spectra are used as probes of the heme and its ligands in ferric and ferrous leghemoglobin. The proximal ligand to the heme iron atom of ferric soybean leghemoglobin is identified as imidazole by comparison of the EPR of leghemoglobin hydroxide, azide, and cyanide with the corresponding derivatives of human hemoglobin. Optical spectra show that ferric soybean leghemoglobin near room temperature is almost entirely in the high spin state. At 77 K the optical spectrum is that of a low spin compound, while at 1.6 K the EPR is that of a low spin form resembling bis-imidazole heme. Acetate binds to ferric leghemoglobin to form a high spin complex as judged from the optical spectrum. The EPR of this complex is that of high spin ferric heme in a nearly axial environment. The complexes of ferrous leghemoglobin with substituted pyridines exhibit optical absorption maxima near 685 nm, whose absorption maxima and extinctions are strongly dependent on the nature of the substitutents of the pyridine ring; electron withdrawing groups on the pyridine ring shift the absorption maxima to lower energy. A crystal field analysis of the EPR of nicotinate derivatives of ferric leghemoblobin demonstrates that the pyridine nitrogen is also bound to the heme iron in the ferric state. These findings lead us to picture leghemoglobin as a somewhat flexible molecule in which the transition region between the E and F helices may act as a hinge, opening a small amount at higher temperature to a stable configuration in which the protein is high spin and can accommodate exogenous ligand molecules and closing at low temperature to a second stable configuration in which the protein is low spin and in which close approach of the E helix permits the distal histidine to become the principal sixth ligand."}
{"id": "PMID:184093", "title": "Synthesis of the mitochondrial inner membrane in cultured Xenopus laevis oocytes.", "content": "The purpose of this study was to investigate the contribution of mitochondrial and cytoplasmic protein synthesis to the biogenesis of cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase EC 1.9.3.1) and rutamycin-sensitive adenosine triphosphatase (ATP phosphohydrolase EC 3.6.1.3) in cultured oocytes of the toad, Xenopus laevis. X. laevis cytochrome oxidase was purified over 23-fold with respect to specific activity and over 29-fold with respect to specific heme a content from oocyte submitochondrial particles. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate separated the enzyme into six subunits with molecular weights of 44,000, 33,000, 23,000, 17,000, 12,000 and 9,500. the synthesis of the three larger subunits is sensitive to chloramphenicol (an inhibitor of mitochondrial protein synthesis), indicating that these subunits are made on mitochondrial ribosomes; the synthesis of the three smaller subunits is sensitive to cycloheximide (an inhibitor of cytoplasmic protein synthesis) and therefore occurs on cytoplasmic ribosomes. X. laevis rutamycin-sensitive ATPase, purified over 19-fold from oocyte submitochondrial pparticles, consists of 10 subunits with molecular weights of 56,000, 53,000, 41,000, 32,000, 29,000, 24,000, 21,000, 17,500 (2), and 11,500 on sodium dodecyl sulfate-polyacrylamide gels. The 29,000, 21,000, and one of the 17,500-dalton polypeptides are synthesized in the presence of cycloheximide and are, therefore, products of mitochondrial protein synthesis; the synthesis of the remaining seven subunits occurs in the presence of chloramphenicol, indicating that these subunits are made on cytoplasmic ribosomes. The synthesis of protein by mitochondria in cultured oocytes appears to be dependent upon cytoplasmic protein synthesis. In the presence of cycloheximide, the mitoribosomal synthesis of the subunits of cytochrome oxidase and rutamycin-sensitive ATPase is detectable only after a prior inhibition of mitochondrial protein synthesis by chloramphenicol. Oocyte mitochondrial ribosomes synthesize at least nine polypeptides after chloramphenicol treatment, three of which are components of neither cytochrome oxidase nor rutamycin-sensitive ATPase.", "contents": "Synthesis of the mitochondrial inner membrane in cultured Xenopus laevis oocytes. The purpose of this study was to investigate the contribution of mitochondrial and cytoplasmic protein synthesis to the biogenesis of cytochrome oxidase (ferrocytochrome c:oxygen oxidoreductase EC 1.9.3.1) and rutamycin-sensitive adenosine triphosphatase (ATP phosphohydrolase EC 3.6.1.3) in cultured oocytes of the toad, Xenopus laevis. X. laevis cytochrome oxidase was purified over 23-fold with respect to specific activity and over 29-fold with respect to specific heme a content from oocyte submitochondrial particles. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate separated the enzyme into six subunits with molecular weights of 44,000, 33,000, 23,000, 17,000, 12,000 and 9,500. the synthesis of the three larger subunits is sensitive to chloramphenicol (an inhibitor of mitochondrial protein synthesis), indicating that these subunits are made on mitochondrial ribosomes; the synthesis of the three smaller subunits is sensitive to cycloheximide (an inhibitor of cytoplasmic protein synthesis) and therefore occurs on cytoplasmic ribosomes. X. laevis rutamycin-sensitive ATPase, purified over 19-fold from oocyte submitochondrial pparticles, consists of 10 subunits with molecular weights of 56,000, 53,000, 41,000, 32,000, 29,000, 24,000, 21,000, 17,500 (2), and 11,500 on sodium dodecyl sulfate-polyacrylamide gels. The 29,000, 21,000, and one of the 17,500-dalton polypeptides are synthesized in the presence of cycloheximide and are, therefore, products of mitochondrial protein synthesis; the synthesis of the remaining seven subunits occurs in the presence of chloramphenicol, indicating that these subunits are made on cytoplasmic ribosomes. The synthesis of protein by mitochondria in cultured oocytes appears to be dependent upon cytoplasmic protein synthesis. In the presence of cycloheximide, the mitoribosomal synthesis of the subunits of cytochrome oxidase and rutamycin-sensitive ATPase is detectable only after a prior inhibition of mitochondrial protein synthesis by chloramphenicol. Oocyte mitochondrial ribosomes synthesize at least nine polypeptides after chloramphenicol treatment, three of which are components of neither cytochrome oxidase nor rutamycin-sensitive ATPase."}
{"id": "PMID:184094", "title": "Structure of glycogen phosphorylase a at 3.0 A resolution and its ligand binding sites at 6 A.", "content": "A model of the polypeptide backbone of the dimer of glycogen phosphorylase a (EC 2.4.1.1) was built from a 3 A resolution electron density map derived from x-ray diffraction analysis of native tetragonal crystals and two heavy atom isomorphous replacement derivatives. Each identical subunit of the dimer has a compact shape with overall dimensions of 85 X 75 X 55 A and is tightly associated with its 2-fold symmetry related subunit. There are three major excursions of the polypeptide chain of one monomer across the 2-fold axis to make extensive contacts with the other subunit. The active site, of which there are two per dimer, is shared between the two subunits at their interface and comprises a pocket-like region within a \"V\"-shaped framework of two alpha helices. Within this region are found the binding sites for the substrates, glucose-1-P and arsenate, a competitive inhibitor, UDP-glucose, and the allosteric effector, AMP. The site of metabolic control, Ser-14 phosphate, is hydrogen-bonded to a side chain on the outside of one of the alpha helices forming the active site and is 15 A from the AMP binding site. Maltoheptaose, a glycogen analogue and substrate for these enzymatically active crystals, binds in a second region of interest. Even at concentrations above its Km, when binding is sufficiently tight that all seven glucose moieties may be discerned, the closest of these is 25 A from the glucose-1-P binding site. We suggest that this polysaccharide binding site may represent a storage site whereby phosphorylase is bound to the glycogen particle in the muscle cell. The polypeptide chain in a third region has the same topological structure as has been observed for the nucleotide binding domains in the dehydrogenases. Adenine or adenosine (but not AMP) bind here in a position similar to the adenine ring of NAD in the dehydrogenases while glucose binds 17 A away in an interior crevice near the center of the monomer.", "contents": "Structure of glycogen phosphorylase a at 3.0 A resolution and its ligand binding sites at 6 A. A model of the polypeptide backbone of the dimer of glycogen phosphorylase a (EC 2.4.1.1) was built from a 3 A resolution electron density map derived from x-ray diffraction analysis of native tetragonal crystals and two heavy atom isomorphous replacement derivatives. Each identical subunit of the dimer has a compact shape with overall dimensions of 85 X 75 X 55 A and is tightly associated with its 2-fold symmetry related subunit. There are three major excursions of the polypeptide chain of one monomer across the 2-fold axis to make extensive contacts with the other subunit. The active site, of which there are two per dimer, is shared between the two subunits at their interface and comprises a pocket-like region within a \"V\"-shaped framework of two alpha helices. Within this region are found the binding sites for the substrates, glucose-1-P and arsenate, a competitive inhibitor, UDP-glucose, and the allosteric effector, AMP. The site of metabolic control, Ser-14 phosphate, is hydrogen-bonded to a side chain on the outside of one of the alpha helices forming the active site and is 15 A from the AMP binding site. Maltoheptaose, a glycogen analogue and substrate for these enzymatically active crystals, binds in a second region of interest. Even at concentrations above its Km, when binding is sufficiently tight that all seven glucose moieties may be discerned, the closest of these is 25 A from the glucose-1-P binding site. We suggest that this polysaccharide binding site may represent a storage site whereby phosphorylase is bound to the glycogen particle in the muscle cell. The polypeptide chain in a third region has the same topological structure as has been observed for the nucleotide binding domains in the dehydrogenases. Adenine or adenosine (but not AMP) bind here in a position similar to the adenine ring of NAD in the dehydrogenases while glucose binds 17 A away in an interior crevice near the center of the monomer."}
{"id": "PMID:184096", "title": "Population density and regulation of cell division in 3T3 cells. I. Inorganic phosphate levels, uptake and release.", "content": "Triggering mechanisms for initiating density dependent inhibition of cell division in 3T3 cell monolayers are activated approximately two to three population doublings prior to cessation of cell division at monolayer confluency. This activation occurs at a critical contact cell density of approximately 8 X 10(3) cells/cm2. During this period there are selective controls on transport and storage of required low molecular weight nutrients. A possible correlation between orthophosphate and rates of cell division has been investigated. We have demonstrated a relationship between cellular concentrations of orthophosphate and initiation of density dependent inhibition of cell division. Prior to critical intercellular contact, the [Pi] in 3T3 is 10 mM. During critical contact, this concentration is quickly reduced to approximately 2 mM and remains at this concentration to confluency. Similar alterations do not occur in Py 3T3 cells, which maintain a concentration of approximately 2 mM Pi regardless of cell density. After confluent 3T3 cells are released from inhibition of cell division the [Pi] must increase several-fold before DNA synthesis commences. These are physiological changes in 3T3 cellular [Pi] as a function of cell density, and cannot be attributed to nutrient depletion, altered transport of Pi into the cell, increased [ATP], or increased [PPi] levels. The controlled modulation of [Pi] may regulate glycolysis and coordinate counter-ion changes (Ca++) may regulate mitochondrial activity.", "contents": "Population density and regulation of cell division in 3T3 cells. I. Inorganic phosphate levels, uptake and release. Triggering mechanisms for initiating density dependent inhibition of cell division in 3T3 cell monolayers are activated approximately two to three population doublings prior to cessation of cell division at monolayer confluency. This activation occurs at a critical contact cell density of approximately 8 X 10(3) cells/cm2. During this period there are selective controls on transport and storage of required low molecular weight nutrients. A possible correlation between orthophosphate and rates of cell division has been investigated. We have demonstrated a relationship between cellular concentrations of orthophosphate and initiation of density dependent inhibition of cell division. Prior to critical intercellular contact, the [Pi] in 3T3 is 10 mM. During critical contact, this concentration is quickly reduced to approximately 2 mM and remains at this concentration to confluency. Similar alterations do not occur in Py 3T3 cells, which maintain a concentration of approximately 2 mM Pi regardless of cell density. After confluent 3T3 cells are released from inhibition of cell division the [Pi] must increase several-fold before DNA synthesis commences. These are physiological changes in 3T3 cellular [Pi] as a function of cell density, and cannot be attributed to nutrient depletion, altered transport of Pi into the cell, increased [ATP], or increased [PPi] levels. The controlled modulation of [Pi] may regulate glycolysis and coordinate counter-ion changes (Ca++) may regulate mitochondrial activity."}
{"id": "PMID:184097", "title": "Species-specific aggregation factor in sponges. VI. Aggregation receptor from the cell surface.", "content": "An aggregation receptor from the siliceous sponge Geodia cydonium has been isolated and purified in an almost pure form. It sediments at about 2-6s, has a buoyant density of 1-51 g/ml in CsCl and elutes from Sephadex G-50 at a Ve/V0 value of 1-311. Chemical analysis revealed that the receptor consists of 81% neutral carbohydrate and 7-5% protein. The activity of the receptor is rapidly destroyed by Na-periodate. The receptor is released from the cell surface after removal of Ca2+ from the medium or after incubation of the cells with trypsin. The depleted cells can be charged again with isolated receptor molecules. The binding of the receptor molecules on the cell surface is prevented in the presence of trypsin. For optimal binding, physiological salt concentrations with respect to NaCl (540 mM NaCl) and Ca2+ ions are necessary. The receptor whose isolation is described in this report, is involved in secondary aggregation processes, which are initiated by a soluble aggregation factor. The primary aggregation of the cells is not influenced by the receptor. Time-course studies with receptor-depleted cells revealed that new aggregation receptor molecules are formed during the aggregation process. By competition experiments it could be shown that high concentrations of soluble aggregation receptor molecules inhibit secondary aggregation. The soluble receptor molecules can complete with surface-bound receptor molecules only if these are not linked with the aggregation factor.", "contents": "Species-specific aggregation factor in sponges. VI. Aggregation receptor from the cell surface. An aggregation receptor from the siliceous sponge Geodia cydonium has been isolated and purified in an almost pure form. It sediments at about 2-6s, has a buoyant density of 1-51 g/ml in CsCl and elutes from Sephadex G-50 at a Ve/V0 value of 1-311. Chemical analysis revealed that the receptor consists of 81% neutral carbohydrate and 7-5% protein. The activity of the receptor is rapidly destroyed by Na-periodate. The receptor is released from the cell surface after removal of Ca2+ from the medium or after incubation of the cells with trypsin. The depleted cells can be charged again with isolated receptor molecules. The binding of the receptor molecules on the cell surface is prevented in the presence of trypsin. For optimal binding, physiological salt concentrations with respect to NaCl (540 mM NaCl) and Ca2+ ions are necessary. The receptor whose isolation is described in this report, is involved in secondary aggregation processes, which are initiated by a soluble aggregation factor. The primary aggregation of the cells is not influenced by the receptor. Time-course studies with receptor-depleted cells revealed that new aggregation receptor molecules are formed during the aggregation process. By competition experiments it could be shown that high concentrations of soluble aggregation receptor molecules inhibit secondary aggregation. The soluble receptor molecules can complete with surface-bound receptor molecules only if these are not linked with the aggregation factor."}
{"id": "PMID:184098", "title": "Synthesis of the inner mitochondrial membrane and the intercalation of respiratory enzymes during the cell cycle of Chlorella.", "content": "The ratio of inner to outer mitochondrial membrane area remains close to 1-8 throughout the cell cycle in synchronized cells of Chlorella fusca var, vacuolata 211-8p. Using estimates of this ratio, together with our previous estimates of mitochondrial surface area, to calculate the absolute area of inner mitochondrial membrane, it is demonstrated that growth of the inner mitochondrial membrane during the cell cycle occupies an extended period and parallels the growth of the whole cell. In contrast, the synthesis of succinate dehydrogenase and cytochrome oxidase is restricted to the last third of the cell cycle. It is concluded that mitochondrial growth involves the intercalation of periodically synthesized respiratory enzymes into membranes made earlier in the cycle, with consequent 5-fold changes in the density of active enzyme molecules in the membrane. These observations are discussed in relation to the control of mitochondiral membrane synthesis, membrane assembly and respiration rate during the cell cycle.", "contents": "Synthesis of the inner mitochondrial membrane and the intercalation of respiratory enzymes during the cell cycle of Chlorella. The ratio of inner to outer mitochondrial membrane area remains close to 1-8 throughout the cell cycle in synchronized cells of Chlorella fusca var, vacuolata 211-8p. Using estimates of this ratio, together with our previous estimates of mitochondrial surface area, to calculate the absolute area of inner mitochondrial membrane, it is demonstrated that growth of the inner mitochondrial membrane during the cell cycle occupies an extended period and parallels the growth of the whole cell. In contrast, the synthesis of succinate dehydrogenase and cytochrome oxidase is restricted to the last third of the cell cycle. It is concluded that mitochondrial growth involves the intercalation of periodically synthesized respiratory enzymes into membranes made earlier in the cycle, with consequent 5-fold changes in the density of active enzyme molecules in the membrane. These observations are discussed in relation to the control of mitochondiral membrane synthesis, membrane assembly and respiration rate during the cell cycle."}
{"id": "PMID:184099", "title": "Neutral protease activity of Rous sarcoma (RSV) transformed chick embryo fibroblasts.", "content": "The proteolytic activities of normal, Schmidt-Ruppin Rous sarcoma virus (SR-RSV) transformed, and infected (RAV) chick embryo fibroblasts (CEF) have been measured by a highly sensitive technique using 3H-acetylated haemoglobin as a substrate. When all 3 types of CEF cells were maintained in serumless media, no differences were detected in the amount of pH 3-4 protease activity released into the media over a 24-h period, and only negligible amounts of pH 7-6 proteolytic activity were found. When normal, transformed, and infected cells were maintained in serumless media and later incubated with 3H-acetylate haemoglobin, a significant proteolysis of the haemoglobin, a 6-fold increase compared to the normal CEF cells, was associated only with plates containing SR-RSV-CEF cells. A fluorescent assay for peptides confirmed that SR-RSV-CEF cells have increased cell-associated proteolytic activity. The net surface charge of the transformed CEF cells was unchanged by maintenance in serumless media but the net surface negativity of the normal and RAV-CEF cells was significantly increased by incubation in media minus serum for 24 h. This suggests that normal CEF cells, maintained in media plus serum, have a substance masking their surface charge which is absent from the surface of transformed cells, possibly because of proteolytic degradation.", "contents": "Neutral protease activity of Rous sarcoma (RSV) transformed chick embryo fibroblasts. The proteolytic activities of normal, Schmidt-Ruppin Rous sarcoma virus (SR-RSV) transformed, and infected (RAV) chick embryo fibroblasts (CEF) have been measured by a highly sensitive technique using 3H-acetylated haemoglobin as a substrate. When all 3 types of CEF cells were maintained in serumless media, no differences were detected in the amount of pH 3-4 protease activity released into the media over a 24-h period, and only negligible amounts of pH 7-6 proteolytic activity were found. When normal, transformed, and infected cells were maintained in serumless media and later incubated with 3H-acetylate haemoglobin, a significant proteolysis of the haemoglobin, a 6-fold increase compared to the normal CEF cells, was associated only with plates containing SR-RSV-CEF cells. A fluorescent assay for peptides confirmed that SR-RSV-CEF cells have increased cell-associated proteolytic activity. The net surface charge of the transformed CEF cells was unchanged by maintenance in serumless media but the net surface negativity of the normal and RAV-CEF cells was significantly increased by incubation in media minus serum for 24 h. This suggests that normal CEF cells, maintained in media plus serum, have a substance masking their surface charge which is absent from the surface of transformed cells, possibly because of proteolytic degradation."}
{"id": "PMID:184100", "title": "Cytochalasin B-induced pseudo-cleavage of mouse oocytes in vitro: asymmetric localization of mitochondria and microvilli associated with a stage-specific response.", "content": "Mouse oocytes are induced by cytochalasin B to undergo 'pseudo-cleavage' in vitro into 2 equally sized and separable compartments. This response to the drug is dependent upon the meiotic state of the oocytes, as well as upon the presence of an intact zona pellucida. The resulting 2 cellular compartments can be completely separated from another and cultured in vitro. Each of the compartments possesses characteristic structural features. The most pronounced structural differences include: (i) the presence of a nucleus (germinal vesicle) and nucleolus in one compartment; (ii) the presence of microvilli on the surface of the anucleate, but not the nucleate, compartment; and (iii) the localization (segregation) of mitochondria at the periphery of the anucleate, but not the nucleate, compartment. The results presented suggest that pseudo-cleavage induced by cytochalasin B arises as a consequence of a limited interaction of the drug with the oocyte surface and/or cortex and that it may represent a topographical dissociation of transporting and non-transporting regions of the membrane. These and other features of mouse oocytes treated with cytochalasin B are of interest in view of the involvement of the oocyte zona pellucida and plasma membrane during meiotic maturation, fertilization, and early embryogenesis.", "contents": "Cytochalasin B-induced pseudo-cleavage of mouse oocytes in vitro: asymmetric localization of mitochondria and microvilli associated with a stage-specific response. Mouse oocytes are induced by cytochalasin B to undergo 'pseudo-cleavage' in vitro into 2 equally sized and separable compartments. This response to the drug is dependent upon the meiotic state of the oocytes, as well as upon the presence of an intact zona pellucida. The resulting 2 cellular compartments can be completely separated from another and cultured in vitro. Each of the compartments possesses characteristic structural features. The most pronounced structural differences include: (i) the presence of a nucleus (germinal vesicle) and nucleolus in one compartment; (ii) the presence of microvilli on the surface of the anucleate, but not the nucleate, compartment; and (iii) the localization (segregation) of mitochondria at the periphery of the anucleate, but not the nucleate, compartment. The results presented suggest that pseudo-cleavage induced by cytochalasin B arises as a consequence of a limited interaction of the drug with the oocyte surface and/or cortex and that it may represent a topographical dissociation of transporting and non-transporting regions of the membrane. These and other features of mouse oocytes treated with cytochalasin B are of interest in view of the involvement of the oocyte zona pellucida and plasma membrane during meiotic maturation, fertilization, and early embryogenesis."}
{"id": "PMID:184102", "title": "Detection and determination of N-nitrosamines by thin-layer chromatography using fluorescamine.", "content": "A novel procedure is described for the detection and determination of N-nitrosamines (NAs) on thin-layer chromatographic plates. Ultraviolet irradiation of NAs on activated plates (silica gel or aluminum oxide) yields primary or secondary amines, which after spraying with fluorescamine reagent give fluorescent or non-fluorescent products, respectively. The majority of the 24 NAs examined afforded NAs, although the volatile dimethyl-, diethyl- and pyrrolidine-N-nitrosamines gave limits of 500, 40, and 40 ng, respectively. Spectrophotometric determinations of the relative fluorescence of 0.1-40 nmoles of NAs gave rise to nearly linear calibration curves when plotted on a log-log scale.", "contents": "Detection and determination of N-nitrosamines by thin-layer chromatography using fluorescamine. A novel procedure is described for the detection and determination of N-nitrosamines (NAs) on thin-layer chromatographic plates. Ultraviolet irradiation of NAs on activated plates (silica gel or aluminum oxide) yields primary or secondary amines, which after spraying with fluorescamine reagent give fluorescent or non-fluorescent products, respectively. The majority of the 24 NAs examined afforded NAs, although the volatile dimethyl-, diethyl- and pyrrolidine-N-nitrosamines gave limits of 500, 40, and 40 ng, respectively. Spectrophotometric determinations of the relative fluorescence of 0.1-40 nmoles of NAs gave rise to nearly linear calibration curves when plotted on a log-log scale."}
{"id": "PMID:184103", "title": "High-performance liquid chromatography of organophosphorus insecticides.", "content": "The high-performance liquid chromatographic behaviour of 23 organophosphorus insecticides has been studied on a stainless-steel column packed with silica gel. It has been stated that the usual classification of organophosphorus compounds into phosphonic, phosphoric, thiophosphoric and dithiophosphoric acid ester types gives some information about their adsorption properties. The chromatographic conditions of the analyses and a method for separation of the stereoisomers of tetrachlorvinphos are presented.", "contents": "High-performance liquid chromatography of organophosphorus insecticides. The high-performance liquid chromatographic behaviour of 23 organophosphorus insecticides has been studied on a stainless-steel column packed with silica gel. It has been stated that the usual classification of organophosphorus compounds into phosphonic, phosphoric, thiophosphoric and dithiophosphoric acid ester types gives some information about their adsorption properties. The chromatographic conditions of the analyses and a method for separation of the stereoisomers of tetrachlorvinphos are presented."}
{"id": "PMID:184104", "title": "Simplified low-pressure high-resolution nucleotide analyser.", "content": "A simple nucleotide analyser was constructed from commercially available components. A 20 cm X 0.4 cm I.D. column of pellicular anion exchanger operating at approximately 20 p.s.i. was found to perform identically with published methods using high-pressure equipment. The eluant was monitored using a variable-wavelength UV monitor. A very simple device for producing variable gradients was employed. The nucleotide analyser was trouble free to operate and the results were both linear and reproducible. Applications to the rapid analysis of nucleotides and the high-sensitivity analysis (approx. 10 pmoles) of cyclic 3',5'-adenosine monophosphate and cyclic 2',3'-guanosine monophosphate and tissue nucleotides are described.", "contents": "Simplified low-pressure high-resolution nucleotide analyser. A simple nucleotide analyser was constructed from commercially available components. A 20 cm X 0.4 cm I.D. column of pellicular anion exchanger operating at approximately 20 p.s.i. was found to perform identically with published methods using high-pressure equipment. The eluant was monitored using a variable-wavelength UV monitor. A very simple device for producing variable gradients was employed. The nucleotide analyser was trouble free to operate and the results were both linear and reproducible. Applications to the rapid analysis of nucleotides and the high-sensitivity analysis (approx. 10 pmoles) of cyclic 3',5'-adenosine monophosphate and cyclic 2',3'-guanosine monophosphate and tissue nucleotides are described."}
{"id": "PMID:184107", "title": "Improvements of a radioimmunoassay for measurement of viral antibody in human sera.", "content": "Modifications were made which increased the sensitivity of a solid-phase radioimmunoassay for serum antibody to human herpesviruses. Quantitation of antibody can be accomplished by referring to standard curve titrations.", "contents": "Improvements of a radioimmunoassay for measurement of viral antibody in human sera. Modifications were made which increased the sensitivity of a solid-phase radioimmunoassay for serum antibody to human herpesviruses. Quantitation of antibody can be accomplished by referring to standard curve titrations."}
{"id": "PMID:184108", "title": "Comparative activity of immunofluorescent antibody and complement-fixing antibody in cytomegalovirus infection.", "content": "Three different tests for detection of antibodies to human cytomegalovirus (CMV), complement fixing with antigen prepared by freeze-thaw disruption (CF-FT) or with antigen prepared by extraction with alkaline glycine buffer (CF-GE) and immunofluorescent staining (FA), were compared in renal transplant recipients and their healthy donors, FA and CF-GE tests yielded positive results at an identical and significantly higher frequency than CF-FT in both donors and recipients. CF-GE and FA performed on donors and recipients predicted all virus shedding post-transplant, whereas CF-FT did not. In the individuals who developed primary infection concurrent with the transplanted kidney, FA developed earlier than other antibodies in about one-half and at the same time in the remainder. In addition, the FA test could be completed more quickly and all sera could be interpreted, which made the FA test more useful than the CF-GE, but both of these tests were clearly superior to CF-FT.", "contents": "Comparative activity of immunofluorescent antibody and complement-fixing antibody in cytomegalovirus infection. Three different tests for detection of antibodies to human cytomegalovirus (CMV), complement fixing with antigen prepared by freeze-thaw disruption (CF-FT) or with antigen prepared by extraction with alkaline glycine buffer (CF-GE) and immunofluorescent staining (FA), were compared in renal transplant recipients and their healthy donors, FA and CF-GE tests yielded positive results at an identical and significantly higher frequency than CF-FT in both donors and recipients. CF-GE and FA performed on donors and recipients predicted all virus shedding post-transplant, whereas CF-FT did not. In the individuals who developed primary infection concurrent with the transplanted kidney, FA developed earlier than other antibodies in about one-half and at the same time in the remainder. In addition, the FA test could be completed more quickly and all sera could be interpreted, which made the FA test more useful than the CF-GE, but both of these tests were clearly superior to CF-FT."}
{"id": "PMID:184109", "title": "Application of freeze-dried, one-day-old chick erythrocytes to viral hemagglutination and hemagglutination-inhibition tests.", "content": "Erythrocytes collected from 1-day-old chicks were stabilized by fixation with formaldehyde and by freeze-drying after treatment with carbon monoxide. Suspensions of freeze-dried erythrocytes in distilled water or physiological saline had a homogeneous bright reddish-purple color. Freeze-dried erythrocytes were compared with fresh erythrocytes for hemagglutination and hemagglutination-inhibition tests for various viruses including rubella, Japanese encephalitis, influenza, mumps, Newcastle disease, and Sendai viruses. After storage at 4 degrees C for 1 year or more, freeze-dried erythrocytes maintained their original appearance and sensitivity to hemagglutination antigens.", "contents": "Application of freeze-dried, one-day-old chick erythrocytes to viral hemagglutination and hemagglutination-inhibition tests. Erythrocytes collected from 1-day-old chicks were stabilized by fixation with formaldehyde and by freeze-drying after treatment with carbon monoxide. Suspensions of freeze-dried erythrocytes in distilled water or physiological saline had a homogeneous bright reddish-purple color. Freeze-dried erythrocytes were compared with fresh erythrocytes for hemagglutination and hemagglutination-inhibition tests for various viruses including rubella, Japanese encephalitis, influenza, mumps, Newcastle disease, and Sendai viruses. After storage at 4 degrees C for 1 year or more, freeze-dried erythrocytes maintained their original appearance and sensitivity to hemagglutination antigens."}
{"id": "PMID:184110", "title": "Replication of murine paramyxoviruses in hamster tracheal organ culture and comparison with standard tissue culture methods.", "content": "Replication of Sendai virus, pneumonia virus of mice, and SV5 was investigated in tracheal organ cultures from 2- to 4-day-old and 2- and 4-week-old hamsters, and viral infectivity in tracheal explants was compared with that in tissue culture monolayers. Explants from 2- to 4-day-old hamsters produced higher titers of the three paramyxoviruses, as detected by hemadsorption with guinea pig and murine erythrocytes in primary rhesus monkey kidney cells. Tracheal cultures from 2- and 4-week-old hamsters yielded 1.5 and 2.5 log10 lower infectivity titers. Infected explants exhibited cytopathological changes that correlated well with cessation of ciliary activity. Viral titers in BHK-21, Vero, and BS-C-1 monolayer cells, the systems commonly used for isolation and propagation of murine paramyxoviruses, were lower than those in 2- to 4-day-old hamster tracheal explants. These observations suggest that hamster trachea organ culture could have practical application as an aid for primary isolation of paramyxoviruses from clinical specimens from rodents with respiratory ailments.", "contents": "Replication of murine paramyxoviruses in hamster tracheal organ culture and comparison with standard tissue culture methods. Replication of Sendai virus, pneumonia virus of mice, and SV5 was investigated in tracheal organ cultures from 2- to 4-day-old and 2- and 4-week-old hamsters, and viral infectivity in tracheal explants was compared with that in tissue culture monolayers. Explants from 2- to 4-day-old hamsters produced higher titers of the three paramyxoviruses, as detected by hemadsorption with guinea pig and murine erythrocytes in primary rhesus monkey kidney cells. Tracheal cultures from 2- and 4-week-old hamsters yielded 1.5 and 2.5 log10 lower infectivity titers. Infected explants exhibited cytopathological changes that correlated well with cessation of ciliary activity. Viral titers in BHK-21, Vero, and BS-C-1 monolayer cells, the systems commonly used for isolation and propagation of murine paramyxoviruses, were lower than those in 2- to 4-day-old hamster tracheal explants. These observations suggest that hamster trachea organ culture could have practical application as an aid for primary isolation of paramyxoviruses from clinical specimens from rodents with respiratory ailments."}
{"id": "PMID:184111", "title": "In vitro action of bombesin and bombesin-like peptides on amylase secretion, calcium efflux, and adenylate cyclase activity in the rat pancreas: a comparison with other secretagogues.", "content": "Bombesin (a tetradecapeptide), the C-terminal nonapeptide of bombesin (bombesin-NP), and litorin (a parent nonapeptide), each stimulated amylase secretion from rat pancreatic fragments. These responses were not affected by atropine. The concentrations that produced half-maximal stumulation of secretion were 0.25 nM for bombesin, 0.30 nM for bombesin-NP, and 0.07 nM for litorin, as compared to 0.12 nM for caerulein and 0.80 muM for the cholinergic agent carbamylcholine. When used at maximal concentrations, bombesin, bombesin-NP, and litorin showed no action on cyclic AMP levels in the presence of 5 mM theophylline. By contrast, caerulein and secretin increased cyclic AMP levels by 27 and 208%, respectively. Bombesin, bombesin-NP, and litorin did not activate adenylate cyclase in a purified pancreatic plasma membrane preparation, whereas caerulein and secretin increased this activity 20 and 16-times, respectively...", "contents": "In vitro action of bombesin and bombesin-like peptides on amylase secretion, calcium efflux, and adenylate cyclase activity in the rat pancreas: a comparison with other secretagogues. Bombesin (a tetradecapeptide), the C-terminal nonapeptide of bombesin (bombesin-NP), and litorin (a parent nonapeptide), each stimulated amylase secretion from rat pancreatic fragments. These responses were not affected by atropine. The concentrations that produced half-maximal stumulation of secretion were 0.25 nM for bombesin, 0.30 nM for bombesin-NP, and 0.07 nM for litorin, as compared to 0.12 nM for caerulein and 0.80 muM for the cholinergic agent carbamylcholine. When used at maximal concentrations, bombesin, bombesin-NP, and litorin showed no action on cyclic AMP levels in the presence of 5 mM theophylline. By contrast, caerulein and secretin increased cyclic AMP levels by 27 and 208%, respectively. Bombesin, bombesin-NP, and litorin did not activate adenylate cyclase in a purified pancreatic plasma membrane preparation, whereas caerulein and secretin increased this activity 20 and 16-times, respectively..."}
{"id": "PMID:184112", "title": "Inhibition of lymphoproliferation by hyperlipoproteinemic plasma.", "content": "Plasma for patients with primary type IV or V hyperlipoproteinemia inhibited [3H]thymidine incorporation by cultured mononuclear leukocytes. This previously unreported abnormality affected mononuclear leukocytes from patients with type IV or V hyperlipoproteinemia and from normal subjects. Patient cells incorporated [3H]thymidine normally when washed and incubated in medium containing normal plasma. Both spontaneous incorporation and stimulated incorporation in response to various mitogens and antigens were inhibited. The inhibitory effect was identified with the chylomicron and very low density lipoprotein fractions isolated from plasma and was concentration-dependent. Lectin used to stimulate cultured cells and [3H]thymidine used to measure responses were not bound to the lipoproteins in appreciable amounts. [3H]-Thymidine incorporation correlated well with morphologic evidence of lymphoproliferation. The mechanism of the inhibitory effect of type IV or V hyperlipoproteinemic plasma upon the response tested was not identified by may be related to interaction between lipoproteins and the cell membranes. We suggest that these lipoproteins may also interfere with the function of other cells.", "contents": "Inhibition of lymphoproliferation by hyperlipoproteinemic plasma. Plasma for patients with primary type IV or V hyperlipoproteinemia inhibited [3H]thymidine incorporation by cultured mononuclear leukocytes. This previously unreported abnormality affected mononuclear leukocytes from patients with type IV or V hyperlipoproteinemia and from normal subjects. Patient cells incorporated [3H]thymidine normally when washed and incubated in medium containing normal plasma. Both spontaneous incorporation and stimulated incorporation in response to various mitogens and antigens were inhibited. The inhibitory effect was identified with the chylomicron and very low density lipoprotein fractions isolated from plasma and was concentration-dependent. Lectin used to stimulate cultured cells and [3H]thymidine used to measure responses were not bound to the lipoproteins in appreciable amounts. [3H]-Thymidine incorporation correlated well with morphologic evidence of lymphoproliferation. The mechanism of the inhibitory effect of type IV or V hyperlipoproteinemic plasma upon the response tested was not identified by may be related to interaction between lipoproteins and the cell membranes. We suggest that these lipoproteins may also interfere with the function of other cells."}
{"id": "PMID:184113", "title": "Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder.", "content": "Vasopressin increases the permeability of the total urinary bladder, an analogue of the mammalian renal collecting duct, to water and small solutes, especially the amide urea. We have observed that three general anesthetic agents of clinical importance, the gases methoxyflurane and halothane and the ultrashortacting barbiturate methohexital, reversibly inhibit vasopressin-stimulated water flow, but do not depress permeability to urea, or the the lipophilic solute diphenylhydantoin. In contrast to their effects in vasopressin-treated bladders, the anesthetics do not inhibit cyclic AMP-stimulated water flow, consistent with an effect on vasopressin-responsive adenylate cyclase. The selectivity of the anesthetic-induced depression of water flow suggests that separate adenylate cyclases and cyclic AMP pools may exist for control of water and urea permeabilities in to toad bladder. Furthermore, theophylline's usual stimulatory effect on water flow, but not its effect on urea permeability, was entirely abolished in methoxyflurane-treated bladders, suggesting that separate phosphodiesterases that control water and urea permeabilities are present as well. We conclude that the majority of water and urea transport takes place via separate pathways across the rate-limiting luminal membrane of the bladder cell, and that separate vasopressin-responsive cellular pools of cyclic AMP appear to control permeability to water and to urea.", "contents": "Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder. Vasopressin increases the permeability of the total urinary bladder, an analogue of the mammalian renal collecting duct, to water and small solutes, especially the amide urea. We have observed that three general anesthetic agents of clinical importance, the gases methoxyflurane and halothane and the ultrashortacting barbiturate methohexital, reversibly inhibit vasopressin-stimulated water flow, but do not depress permeability to urea, or the the lipophilic solute diphenylhydantoin. In contrast to their effects in vasopressin-treated bladders, the anesthetics do not inhibit cyclic AMP-stimulated water flow, consistent with an effect on vasopressin-responsive adenylate cyclase. The selectivity of the anesthetic-induced depression of water flow suggests that separate adenylate cyclases and cyclic AMP pools may exist for control of water and urea permeabilities in to toad bladder. Furthermore, theophylline's usual stimulatory effect on water flow, but not its effect on urea permeability, was entirely abolished in methoxyflurane-treated bladders, suggesting that separate phosphodiesterases that control water and urea permeabilities are present as well. We conclude that the majority of water and urea transport takes place via separate pathways across the rate-limiting luminal membrane of the bladder cell, and that separate vasopressin-responsive cellular pools of cyclic AMP appear to control permeability to water and to urea."}
{"id": "PMID:184117", "title": "Viral infections.", "content": "Although rubella is the only virus which can be regarded in the strict sense of the term a teratogen, there is no convincing evidence that other viruses can cause fetal damage of varying severity. The risk to the fetus appears to depend on the nature of the infectious agent, the maternal immune status and the gestational age when infection takes place. The possibility that subclinical maternal infections may cause damage must not be overlooked. As some of the viruses referred to can cause damage after the period of organogenesis, the use of the term 'teratogenic efect' in relation to viral infections is considered to be inappropriate.", "contents": "Viral infections. Although rubella is the only virus which can be regarded in the strict sense of the term a teratogen, there is no convincing evidence that other viruses can cause fetal damage of varying severity. The risk to the fetus appears to depend on the nature of the infectious agent, the maternal immune status and the gestational age when infection takes place. The possibility that subclinical maternal infections may cause damage must not be overlooked. As some of the viruses referred to can cause damage after the period of organogenesis, the use of the term 'teratogenic efect' in relation to viral infections is considered to be inappropriate."}
{"id": "PMID:184120", "title": "Relations between behavioral arousal and plasma cortisol levels in monkeys performing repeated free-operant avoidance sessions.", "content": "The commonly believed hypothesis that increases in adrenocorticoid levels sensitively reflect behavioral arousal was tested by subjecting monkeys to repeated sessions of free-operant avoidance; these sessions produced varying degrees of behavioral arousal over time, which were quantified by a behavioral scoring technique. Cortisol was reliably elevated only in the most aroused subjects early in the first avoidance session. Although subjects were still aroused later in the session, cortisol had returned to basal levels. During subsequent avoidance sessions, cortisol returned to basal levels and did not increase significantly even when arousal was further manipulated by the superimposition of unavoidable shock during the final avoidance session. The addition of unavoidable shock was associated with a significant correlation between arousal, as reflected by increases in response rate, and magnitude of change, usually decreases, in mean cortisol levels. The frequent occurrence of dissociations between cortisol levels and behavioral arousal, as reflected by behavioral score, operant rate, and shock frequency, indicates that cortisol levels are of little use as a neuroendocrine index of arousal.", "contents": "Relations between behavioral arousal and plasma cortisol levels in monkeys performing repeated free-operant avoidance sessions. The commonly believed hypothesis that increases in adrenocorticoid levels sensitively reflect behavioral arousal was tested by subjecting monkeys to repeated sessions of free-operant avoidance; these sessions produced varying degrees of behavioral arousal over time, which were quantified by a behavioral scoring technique. Cortisol was reliably elevated only in the most aroused subjects early in the first avoidance session. Although subjects were still aroused later in the session, cortisol had returned to basal levels. During subsequent avoidance sessions, cortisol returned to basal levels and did not increase significantly even when arousal was further manipulated by the superimposition of unavoidable shock during the final avoidance session. The addition of unavoidable shock was associated with a significant correlation between arousal, as reflected by increases in response rate, and magnitude of change, usually decreases, in mean cortisol levels. The frequent occurrence of dissociations between cortisol levels and behavioral arousal, as reflected by behavioral score, operant rate, and shock frequency, indicates that cortisol levels are of little use as a neuroendocrine index of arousal."}
{"id": "PMID:184118", "title": "Hypnotic efficacy of triazolam: sleep laboratory evaluation of intermediate-term effectiveness.", "content": "Triazolam (U-33030), an investigational hypnotic drug, was evaluated in seven insomniac subjects in the sleep laboratory. The protocol consisted of 22 consecutive nights: four placebo nights for adaptation and baseline, two weeks of drug administration (0.5 mg triazolam) for short- and intermediate-term drug effectiveness, and four placebo nights for withdrawal effects. With short-term drug use, both sleep induction and sleep maintenance improved, with total wake time decreasing markedly--a 45 per cent decrease from baseline. At the end of two weeks of drug use, none of the efficacy parameters was significantly decreased from baseline; there was only a 17 per cent decrease in total wake time. Following drug withdrawal, sleep difficulty significantly increased above baseline levels. Two of the subjects experienced episodes of amnesia during the drug administration period. The per cent of REM sleep decreased significantly during both short and intermediate drug conditions. Following drug withdrawal, the per cent of REM sleep was similar to baseline. Slow-wave (stages 3 and 4) sleep was significantly decreased for both drug conditions; and following drug withdrawal, it returned completely to the baseline leve. These data indicate that triazolam is effective for short-term use, loses most of its effectiveness with intermediate-term use, and its withdrawal is followed by a significant sorsening of sleep. These findings are discussed in relation to the potential labeling and promotion of triazolam. Finally, the findings of amnesia associated with triazolam administration need to be more thoroughly evaluated.", "contents": "Hypnotic efficacy of triazolam: sleep laboratory evaluation of intermediate-term effectiveness. Triazolam (U-33030), an investigational hypnotic drug, was evaluated in seven insomniac subjects in the sleep laboratory. The protocol consisted of 22 consecutive nights: four placebo nights for adaptation and baseline, two weeks of drug administration (0.5 mg triazolam) for short- and intermediate-term drug effectiveness, and four placebo nights for withdrawal effects. With short-term drug use, both sleep induction and sleep maintenance improved, with total wake time decreasing markedly--a 45 per cent decrease from baseline. At the end of two weeks of drug use, none of the efficacy parameters was significantly decreased from baseline; there was only a 17 per cent decrease in total wake time. Following drug withdrawal, sleep difficulty significantly increased above baseline levels. Two of the subjects experienced episodes of amnesia during the drug administration period. The per cent of REM sleep decreased significantly during both short and intermediate drug conditions. Following drug withdrawal, the per cent of REM sleep was similar to baseline. Slow-wave (stages 3 and 4) sleep was significantly decreased for both drug conditions; and following drug withdrawal, it returned completely to the baseline leve. These data indicate that triazolam is effective for short-term use, loses most of its effectiveness with intermediate-term use, and its withdrawal is followed by a significant sorsening of sleep. These findings are discussed in relation to the potential labeling and promotion of triazolam. Finally, the findings of amnesia associated with triazolam administration need to be more thoroughly evaluated."}
{"id": "PMID:184119", "title": "Absorption and biotransfomation of cholecalciferol in drug-induced osteomalacia.", "content": "The gastrointestinal absorption of vitamin D3 and its biotransformation to 25-hydroxycholecalciferol was studied in patients with drug-induced osteomalacia. The mean coefficient of absorption was virtually identical in the drug-treated group (82.8%) and the control (83.8%). The biotransformation of vitamin D3 to 25-hydroxycholecalciferol was significantly accelerated (P less than 0.03) in the drug-treated group compared to the control group. These data suggest that vitamin D absorption is not significantly altered but that biotransformation of vitamin D3 to 25-hydroxycholecalciferol is accelerated in drug-induced osteomalacia.", "contents": "Absorption and biotransfomation of cholecalciferol in drug-induced osteomalacia. The gastrointestinal absorption of vitamin D3 and its biotransformation to 25-hydroxycholecalciferol was studied in patients with drug-induced osteomalacia. The mean coefficient of absorption was virtually identical in the drug-treated group (82.8%) and the control (83.8%). The biotransformation of vitamin D3 to 25-hydroxycholecalciferol was significantly accelerated (P less than 0.03) in the drug-treated group compared to the control group. These data suggest that vitamin D absorption is not significantly altered but that biotransformation of vitamin D3 to 25-hydroxycholecalciferol is accelerated in drug-induced osteomalacia."}
{"id": "PMID:184121", "title": "Kinetics of irreversible activation of adenylate cyclase of fat cell membranes by phosphonium and phosphoramidate analogs of gtp1.", "content": "The ability of guanylylimidodiphosphate (GMP=P(NH)P) and guanylylmethylenediphosphonate (GMP-P(CH2)P) to activate adenylate cyclase activity has been studied by incubating these analogs with fat cell membranes followed by thorough washing of the membranes before assay of enzyme activity. GMP-P(NH)P is hydrolyzed by membrane preparations from several tissues. A pyruvate kinase regenerating system maintains the concentration of GMP-P(NH)P and thereby augments the ability of suboptimal concentrations of GMP-P(NH)P to activate adenylate cyclase. GTP inhibits activation of fat cell membrane adenylate cyclase by GMP-P(NH)P but this inhibition is overcome by time. This is consistent with the virtually irreversible nature of the GMP-P(NH)P activation, and with the inability of GTP to reverse the stimulated state of the enzyme. Although the initial rate of enzyme activation is highly dependent on the concentration of GMP-P(NH)P, with increasing times of incubation nearly the same maximal extent of activation is seen over a wide range of concentrations. Thus, it is not possible to estimate true affinity constants (at equilibrium) for GMP-P(NH)P, as anticipated from the virtually irreversible character of the activation process.", "contents": "Kinetics of irreversible activation of adenylate cyclase of fat cell membranes by phosphonium and phosphoramidate analogs of gtp1. The ability of guanylylimidodiphosphate (GMP=P(NH)P) and guanylylmethylenediphosphonate (GMP-P(CH2)P) to activate adenylate cyclase activity has been studied by incubating these analogs with fat cell membranes followed by thorough washing of the membranes before assay of enzyme activity. GMP-P(NH)P is hydrolyzed by membrane preparations from several tissues. A pyruvate kinase regenerating system maintains the concentration of GMP-P(NH)P and thereby augments the ability of suboptimal concentrations of GMP-P(NH)P to activate adenylate cyclase. GTP inhibits activation of fat cell membrane adenylate cyclase by GMP-P(NH)P but this inhibition is overcome by time. This is consistent with the virtually irreversible nature of the GMP-P(NH)P activation, and with the inability of GTP to reverse the stimulated state of the enzyme. Although the initial rate of enzyme activation is highly dependent on the concentration of GMP-P(NH)P, with increasing times of incubation nearly the same maximal extent of activation is seen over a wide range of concentrations. Thus, it is not possible to estimate true affinity constants (at equilibrium) for GMP-P(NH)P, as anticipated from the virtually irreversible character of the activation process."}
{"id": "PMID:184122", "title": "Immunohistochemical localization of cyclic nucleotides during testicular development.", "content": "The potential role of cyclic nucleotides in rat testicular development was evaluated by measuring tissue levels of cyclic AMP and cyclic GMP during a time of rapid testicular growth. The levels of the nucleotides were correlated with their distribution in various cell types as well as intracellularly by an immunocytochemical technique. The concentration of cyclic AMP was high during the infantile phase, fell steadily to a nadir prior to puberty and then increased through sexual maturation. Cyclic GMP levels were also elevated during the infantile phase and decreased steadily through sexual maturation. Early in development the distribution patterns for the two cyclic nucleotides were quite similar with fluorescence in almost all cell types. With maturation, cyclic AMP was localized within tubules, primarily in Sertoli cells and spermatogenia, and was observed in cells in the intertubular area. In the mature testis, cyclic GMP fluorescence was associated with cells representative of most stages of spermatogenesis. Cyclic GMP was localized in nuclear elements of many cell types: in nucleoli of Sertoli cells, spermatogonia and of cells in the intertubular area. Staining was also observed along pachytene chromosomes and in a reticular nuclear pattern in a number of cell types. Cyclic AMP was seen in nuclear elements of certain cells, particularly early in testicular development, but the staining pattern was more indistinct than that of cyclic GMP. The distribution patterns of nucleotides at several stages of testicular development suggest that these compounds may be associated with cellular events related to hormone-dependent maturation of the testis.", "contents": "Immunohistochemical localization of cyclic nucleotides during testicular development. The potential role of cyclic nucleotides in rat testicular development was evaluated by measuring tissue levels of cyclic AMP and cyclic GMP during a time of rapid testicular growth. The levels of the nucleotides were correlated with their distribution in various cell types as well as intracellularly by an immunocytochemical technique. The concentration of cyclic AMP was high during the infantile phase, fell steadily to a nadir prior to puberty and then increased through sexual maturation. Cyclic GMP levels were also elevated during the infantile phase and decreased steadily through sexual maturation. Early in development the distribution patterns for the two cyclic nucleotides were quite similar with fluorescence in almost all cell types. With maturation, cyclic AMP was localized within tubules, primarily in Sertoli cells and spermatogenia, and was observed in cells in the intertubular area. In the mature testis, cyclic GMP fluorescence was associated with cells representative of most stages of spermatogenesis. Cyclic GMP was localized in nuclear elements of many cell types: in nucleoli of Sertoli cells, spermatogonia and of cells in the intertubular area. Staining was also observed along pachytene chromosomes and in a reticular nuclear pattern in a number of cell types. Cyclic AMP was seen in nuclear elements of certain cells, particularly early in testicular development, but the staining pattern was more indistinct than that of cyclic GMP. The distribution patterns of nucleotides at several stages of testicular development suggest that these compounds may be associated with cellular events related to hormone-dependent maturation of the testis."}
{"id": "PMID:184123", "title": "Induction of ornithine decarboxylase in Reuber H35 rat hepatoma cells.", "content": "Stimuli known to induce tyrosine aminotransferase in H35 cells were tested relative to their ability to induce ornithine decarboxylase, the initial enzyme in the polyamine biosynthetic pathway. Dibutyryl cyclic AMP (0.5 mM), parachlorophenylthio-cyclic AMP (0.1 mM) and dexamethasone (1 muM) stimulated the activity of ornithine decarboxylase 7- to 8-fold by 5 hr of induction. There was a delay of 1 hr before any increase in enzyme activity was detectable. Insulin administered alone failed to significantly change ornithine decarboxylase activity. The ability of dibutyryl cyclic AMP to elevate ornithine decarboxylase activity was found to be concentration-dependent, and a dose-response relationship very similar to that for the induction of tyrosine aminotransferase by dibutyryl cyclic AMP was observed in these cells. The ability of various 8-substituted cyclic AMP analogues to increase the activity of ornithine decarboxylase was correlated with their ability to activate purified protein kinase.", "contents": "Induction of ornithine decarboxylase in Reuber H35 rat hepatoma cells. Stimuli known to induce tyrosine aminotransferase in H35 cells were tested relative to their ability to induce ornithine decarboxylase, the initial enzyme in the polyamine biosynthetic pathway. Dibutyryl cyclic AMP (0.5 mM), parachlorophenylthio-cyclic AMP (0.1 mM) and dexamethasone (1 muM) stimulated the activity of ornithine decarboxylase 7- to 8-fold by 5 hr of induction. There was a delay of 1 hr before any increase in enzyme activity was detectable. Insulin administered alone failed to significantly change ornithine decarboxylase activity. The ability of dibutyryl cyclic AMP to elevate ornithine decarboxylase activity was found to be concentration-dependent, and a dose-response relationship very similar to that for the induction of tyrosine aminotransferase by dibutyryl cyclic AMP was observed in these cells. The ability of various 8-substituted cyclic AMP analogues to increase the activity of ornithine decarboxylase was correlated with their ability to activate purified protein kinase."}
{"id": "PMID:184124", "title": "Lithium-angiotensin interaction in rat neurohypophysis.", "content": "The effects of various concentrations of lithium upon basal and angiotensin-stimulated cyclic AMP accumulation were studied in isolated rat neurohypophysis. High doses of lithium diminished significantly the spontaneous accumulation of the nucleotide. This effect was not influenced by pre-incubation. Angiotensin-stimulated accumulation was inhibited by lithium at a dose which did not interfere with the basal accumulation of cyclic AMP. The possible physiological significance and mechanism of action are discussed.", "contents": "Lithium-angiotensin interaction in rat neurohypophysis. The effects of various concentrations of lithium upon basal and angiotensin-stimulated cyclic AMP accumulation were studied in isolated rat neurohypophysis. High doses of lithium diminished significantly the spontaneous accumulation of the nucleotide. This effect was not influenced by pre-incubation. Angiotensin-stimulated accumulation was inhibited by lithium at a dose which did not interfere with the basal accumulation of cyclic AMP. The possible physiological significance and mechanism of action are discussed."}
{"id": "PMID:184125", "title": "Regulation of adenosine 3':5'-monophosphate content of human astrocytoma cells: desensitization to catecholamines and prostaglandins.", "content": "Human astrocytoma cells (1321N1) exhibit adenylate cyclase activities coupled to independent receptors for catecholamines and prostaglandins of the E-series. Exposure of the cells to either norepinephrine or prostaglandin E1 (PGE1) results in an initial rapid accumulation of cyclic AMP but also results in a progressive loss of responsiveness of the cells to agonists. Initially, the desensitization is in large part agonist-specific. However, with continued exposure to high concentrations of norepinephrine, partial loss of responsiveness to PGE1 occurs, and vice versa. The mechanism underlying this phenomenon does not appear to involve inactivation of the effectors, formation of an inhibitory substance in the culture medium or an increase in the rate of excretion of cyclic AMP from the cell. Blockade of protein synthesis (85%) by 5 mug/ml cycloheximide did not change the rate or extent of desensitization. When desensitized cells were incubated in the presence of the effectors, responsiveness was essentially completely recovered with a t1/2 of 5-7 hr. Cycloheximide recovery reduced. Norepinephrine-induced desensitization to either norepinephrine or PGE1 was blocked by sotalol, a beta receptor blocking agent. Incubation of the cells with dibutyryl cyclic AMP caused desensitization to both norepinephrine and PGE). The results suggest that catecholamine-induced desensitization occurs as a result of interaction of the agonist with the same receptor that is linked to activation of adenylate cyclase. Cyclic AMP appears to mediate at least the non-specific aspect of agonist-induced desensitization.", "contents": "Regulation of adenosine 3':5'-monophosphate content of human astrocytoma cells: desensitization to catecholamines and prostaglandins. Human astrocytoma cells (1321N1) exhibit adenylate cyclase activities coupled to independent receptors for catecholamines and prostaglandins of the E-series. Exposure of the cells to either norepinephrine or prostaglandin E1 (PGE1) results in an initial rapid accumulation of cyclic AMP but also results in a progressive loss of responsiveness of the cells to agonists. Initially, the desensitization is in large part agonist-specific. However, with continued exposure to high concentrations of norepinephrine, partial loss of responsiveness to PGE1 occurs, and vice versa. The mechanism underlying this phenomenon does not appear to involve inactivation of the effectors, formation of an inhibitory substance in the culture medium or an increase in the rate of excretion of cyclic AMP from the cell. Blockade of protein synthesis (85%) by 5 mug/ml cycloheximide did not change the rate or extent of desensitization. When desensitized cells were incubated in the presence of the effectors, responsiveness was essentially completely recovered with a t1/2 of 5-7 hr. Cycloheximide recovery reduced. Norepinephrine-induced desensitization to either norepinephrine or PGE1 was blocked by sotalol, a beta receptor blocking agent. Incubation of the cells with dibutyryl cyclic AMP caused desensitization to both norepinephrine and PGE). The results suggest that catecholamine-induced desensitization occurs as a result of interaction of the agonist with the same receptor that is linked to activation of adenylate cyclase. Cyclic AMP appears to mediate at least the non-specific aspect of agonist-induced desensitization."}
{"id": "PMID:184130", "title": "Survival of foot-and-mouth disease virus in cheese.", "content": "Persistence of foot-and-mouth disease virus during the manufacture of Cheddar, Mozzarella, Camembert cheese prepared from milk of cows experimentally infected with the virus was studied. Cheese samples were made on a laboratory scale with commercial lactic acid starter cultures and the microbial protease MARZYME as a coagulant. Milk was heated at different temperatures for different intervals before it was made into cheese. Food-and-mouth disease virus survived the acidic conditions of Cheddar and Camembert cheese processing but not that of Mozzarella. Foot-and-mouth disease virus survived processing but not curing for 30 days in Cheddar cheese preparaed from heated milk. However, the virus survived curing for 60 days but not for 120 days in cheese (pH 5) prepared from unheated milk. Foot-and-mouth disease virus survived in Camembert cheese (pH 5) for 21 days at 2 C but not for 35 days.", "contents": "Survival of foot-and-mouth disease virus in cheese. Persistence of foot-and-mouth disease virus during the manufacture of Cheddar, Mozzarella, Camembert cheese prepared from milk of cows experimentally infected with the virus was studied. Cheese samples were made on a laboratory scale with commercial lactic acid starter cultures and the microbial protease MARZYME as a coagulant. Milk was heated at different temperatures for different intervals before it was made into cheese. Food-and-mouth disease virus survived the acidic conditions of Cheddar and Camembert cheese processing but not that of Mozzarella. Foot-and-mouth disease virus survived processing but not curing for 30 days in Cheddar cheese preparaed from heated milk. However, the virus survived curing for 60 days but not for 120 days in cheese (pH 5) prepared from unheated milk. Foot-and-mouth disease virus survived in Camembert cheese (pH 5) for 21 days at 2 C but not for 35 days."}
{"id": "PMID:184126", "title": "Regulation of adenosine 3':5'-monophosphate content of human astrocytoma cells: mechanism of agonist-specific desensitization.", "content": "The mechanism underlying agonist-induced loss of responsiveness to catecholamines and prostaglandins has been investigated in human astrocytoma cells. Pulse-labeling of the cells with [3H] adenine during the time course of exposure to either norepinephrine or prostaglandin E1 (PGE1) demonstrated a reduction of the rate of incorporation of label into cyclic AMP within 5 min after exposure of the cells to either agonist. The loss of responsiveness observed by this technique was essentially agonist-specific during the first 30 min of exposure of the cells to either norepinephrine or PGE1. The rate constant for degradation of cyclic AMP throughout a 60 min exposure to either norepinephrine or PGE1 did not change suggesting that loss of responsiveness is not related to increased phosphodiesterase activity. The results are discussed in terms of a standard theoretical model for the regulation of the steady state level of an intermediate in a reaction sequence in which the rate of synthesis of the intermediate follows zero order kinetics and the rate of degradation follows first order kinetics. The hypothesis is put forth that agonist-induced desensitization is caused by an agonist-specific reduction in the rate of synthesis of cyclic AMP that follows rapidly after the initial stimulation of adenylate cyclase activity.", "contents": "Regulation of adenosine 3':5'-monophosphate content of human astrocytoma cells: mechanism of agonist-specific desensitization. The mechanism underlying agonist-induced loss of responsiveness to catecholamines and prostaglandins has been investigated in human astrocytoma cells. Pulse-labeling of the cells with [3H] adenine during the time course of exposure to either norepinephrine or prostaglandin E1 (PGE1) demonstrated a reduction of the rate of incorporation of label into cyclic AMP within 5 min after exposure of the cells to either agonist. The loss of responsiveness observed by this technique was essentially agonist-specific during the first 30 min of exposure of the cells to either norepinephrine or PGE1. The rate constant for degradation of cyclic AMP throughout a 60 min exposure to either norepinephrine or PGE1 did not change suggesting that loss of responsiveness is not related to increased phosphodiesterase activity. The results are discussed in terms of a standard theoretical model for the regulation of the steady state level of an intermediate in a reaction sequence in which the rate of synthesis of the intermediate follows zero order kinetics and the rate of degradation follows first order kinetics. The hypothesis is put forth that agonist-induced desensitization is caused by an agonist-specific reduction in the rate of synthesis of cyclic AMP that follows rapidly after the initial stimulation of adenylate cyclase activity."}
{"id": "PMID:184127", "title": "Catecholamine-mediated elevation of cyclic GMP in the rat C-6 glioma cell line.", "content": "Catecholamines cause an elevation of both cyclic GMP and cyclic AMP levels in the rat C-6 glioma cell line. The response is mediated by a beta-receptor, with a Ka for stimulation of cyclic GMP of 2.6 X 10(-7)M. Maximum levels of cyclic GMP are reached by 5 min. whereas cyclic AMP levels are maximal by 10 min. Removal of calcium decreases the cyclic GMP elevation by 60%. Refractoriness to a second treatment with catecholamine develops for both responses. Catecholamine sensitivity of the cyclic GMP-generating system appears in the cells only as they start to contact and enter the stationary growth phase. In contrast to the effects of catecholamines, cholinergic agonists have no effect on either cyclic GMP or cyclic AMP levels.", "contents": "Catecholamine-mediated elevation of cyclic GMP in the rat C-6 glioma cell line. Catecholamines cause an elevation of both cyclic GMP and cyclic AMP levels in the rat C-6 glioma cell line. The response is mediated by a beta-receptor, with a Ka for stimulation of cyclic GMP of 2.6 X 10(-7)M. Maximum levels of cyclic GMP are reached by 5 min. whereas cyclic AMP levels are maximal by 10 min. Removal of calcium decreases the cyclic GMP elevation by 60%. Refractoriness to a second treatment with catecholamine develops for both responses. Catecholamine sensitivity of the cyclic GMP-generating system appears in the cells only as they start to contact and enter the stationary growth phase. In contrast to the effects of catecholamines, cholinergic agonists have no effect on either cyclic GMP or cyclic AMP levels."}
{"id": "PMID:184133", "title": "Preoperative management of glucocorticoid-dependent pedodontic patients.", "content": "Patients with adrenal insufficiency, allergic disorders, blood dyscrasias, collagen, malignant, and gastrointestinal diseases, and renal disorders may be receiving long-term courses of glucocorticoids; mismanagement could result in Addisonian crisis. If dental procedures for these patients involve moderate to severe stress, increases in the dosages of glucocorticoids shoudl be instituted before dental treatment begins.", "contents": "Preoperative management of glucocorticoid-dependent pedodontic patients. Patients with adrenal insufficiency, allergic disorders, blood dyscrasias, collagen, malignant, and gastrointestinal diseases, and renal disorders may be receiving long-term courses of glucocorticoids; mismanagement could result in Addisonian crisis. If dental procedures for these patients involve moderate to severe stress, increases in the dosages of glucocorticoids shoudl be instituted before dental treatment begins."}
{"id": "PMID:184128", "title": "Studies on the stimulation of cAMP metabolism by heparin solutions containing benzyl alcohol.", "content": "Heparin solutions containing benzyl alcohol as a preservative increase intracellular cAMP concentrations in human lymphocytes by as much as 5 fold. Similar changes but of a lesser magnitude were also observed in human polymorphonuclear leukocytes and platelets and rabbit alveolar macrophages. Further analysis demonstrated that benzyl alcohol used as a preservative was responsible for this finding and that heparin per se had no effect on cAMP metabolism. The cAMP response to benzyl alcohol was a time- and dose-dependent process. In human peripheral blood lymphocytes, cAMP levels increased in a linear fashion over a benzyl alcohol concentration range from 0.015-0.30% (v/v). The increased cAMP concentrations in lymphocytes as measured by radioimmunoassay were not due to formation of a cross-reacting adenosine-alcohol adduct since the immunoreactive material produced was destroyed by phosphodiesterase and co-migrated with 3H-cAMP in thin layer chromatographic studies. Concentrations of benzyl alcohol which affect cAMP metabolism are commonly present in biologic studies employing heparin solutions. In view of these findings certain previously described effects of heparin may need to be reinterpreted and in the future heparin solutions containing benzyl alcohol should not be used when studying biologic processes known to be influenced by alterations in cAMP metabolism.", "contents": "Studies on the stimulation of cAMP metabolism by heparin solutions containing benzyl alcohol. Heparin solutions containing benzyl alcohol as a preservative increase intracellular cAMP concentrations in human lymphocytes by as much as 5 fold. Similar changes but of a lesser magnitude were also observed in human polymorphonuclear leukocytes and platelets and rabbit alveolar macrophages. Further analysis demonstrated that benzyl alcohol used as a preservative was responsible for this finding and that heparin per se had no effect on cAMP metabolism. The cAMP response to benzyl alcohol was a time- and dose-dependent process. In human peripheral blood lymphocytes, cAMP levels increased in a linear fashion over a benzyl alcohol concentration range from 0.015-0.30% (v/v). The increased cAMP concentrations in lymphocytes as measured by radioimmunoassay were not due to formation of a cross-reacting adenosine-alcohol adduct since the immunoreactive material produced was destroyed by phosphodiesterase and co-migrated with 3H-cAMP in thin layer chromatographic studies. Concentrations of benzyl alcohol which affect cAMP metabolism are commonly present in biologic studies employing heparin solutions. In view of these findings certain previously described effects of heparin may need to be reinterpreted and in the future heparin solutions containing benzyl alcohol should not be used when studying biologic processes known to be influenced by alterations in cAMP metabolism."}
{"id": "PMID:184129", "title": "Stimulation of myocardial contractility by a new cyclic nucleotide analog, 8-(benzylthio)-N6-n-butyladenosine cyclic 3',5'-phosphate (SQ 80122).", "content": "The cyclic nucleotide analog, 8-(benzylthio)-N6-n-butyladenosine cyclic 3',5'-phosphate (SQ 80122) increases contractile force of excised cat right ventricular papillary muscle and stimulates myocardial contractility in the anesthetized dog. The inotropic action of this compound is independent of catecholamines and stimulation of beta-adrenergic receptors in the heart.", "contents": "Stimulation of myocardial contractility by a new cyclic nucleotide analog, 8-(benzylthio)-N6-n-butyladenosine cyclic 3',5'-phosphate (SQ 80122). The cyclic nucleotide analog, 8-(benzylthio)-N6-n-butyladenosine cyclic 3',5'-phosphate (SQ 80122) increases contractile force of excised cat right ventricular papillary muscle and stimulates myocardial contractility in the anesthetized dog. The inotropic action of this compound is independent of catecholamines and stimulation of beta-adrenergic receptors in the heart."}
{"id": "PMID:184134", "title": "Hypersensitivity to histamine and systemic anaphylaxis in mice with pharmacologic beta adrenergic blockade: protection by nucleotides.", "content": "The effects of exogenous nucleotides on the histamine hypersensitivity of pharmacologically beta-blocked mice were investigated. Female HLA-SW (ICR) mice, 27-29 gm, were injected intraperitoneally with 20 to 100 mug of propranolol 45 min before intraperitoneal challenge with 1 mg histamine. These animals had a mortality which averaged approximately 80%. At various time intervals before histamine, doses of from 0.5 to 12 mumoles of nucleotides were administered intravenously. Noncyclic nucleotides, adenosine, adenosine 5'-monophosphate (AMP), and guanosine 5'-monophosphate (GMP) showed clear, dose-response protection against histamine death of propranolol-treated mice when they were given 45 to 90 min before histamine. Cyclic AMP showed significant protection only when it was given at a dose of 8 mumoles 45 to 90 min before histamine, and lower or higher doses gave equivocal or no protection. Cyclic GMP WAS Not protective at any dose tested. Propranolol treatment also produced enhanced sensitivity to passive systemic anaphylaxis. Mice were passively sensitized by intraperitoneal injection of mouse anti-egg albumin antibody 6 hr before intravenous challenge with 0.5 mg egg albumin. The mortality from anaphylaxis in the group treated with 20 mug propranolol 45 min before antigen challenge increased to 83%, while that of the group not given propranolol was only 10%. Nucleotides were given intravenously 45 min before antigen challenge. The nucleotides that protected mice from death due to histamine challenge also protected them from death due to systemic anaphylaxis. These protective nucleotides were the same nucleotides that had been reported previously to be protective against Bordetella pertussis-induced hypersensitivity to histamine and anaphylaxis.", "contents": "Hypersensitivity to histamine and systemic anaphylaxis in mice with pharmacologic beta adrenergic blockade: protection by nucleotides. The effects of exogenous nucleotides on the histamine hypersensitivity of pharmacologically beta-blocked mice were investigated. Female HLA-SW (ICR) mice, 27-29 gm, were injected intraperitoneally with 20 to 100 mug of propranolol 45 min before intraperitoneal challenge with 1 mg histamine. These animals had a mortality which averaged approximately 80%. At various time intervals before histamine, doses of from 0.5 to 12 mumoles of nucleotides were administered intravenously. Noncyclic nucleotides, adenosine, adenosine 5'-monophosphate (AMP), and guanosine 5'-monophosphate (GMP) showed clear, dose-response protection against histamine death of propranolol-treated mice when they were given 45 to 90 min before histamine. Cyclic AMP showed significant protection only when it was given at a dose of 8 mumoles 45 to 90 min before histamine, and lower or higher doses gave equivocal or no protection. Cyclic GMP WAS Not protective at any dose tested. Propranolol treatment also produced enhanced sensitivity to passive systemic anaphylaxis. Mice were passively sensitized by intraperitoneal injection of mouse anti-egg albumin antibody 6 hr before intravenous challenge with 0.5 mg egg albumin. The mortality from anaphylaxis in the group treated with 20 mug propranolol 45 min before antigen challenge increased to 83%, while that of the group not given propranolol was only 10%. Nucleotides were given intravenously 45 min before antigen challenge. The nucleotides that protected mice from death due to histamine challenge also protected them from death due to systemic anaphylaxis. These protective nucleotides were the same nucleotides that had been reported previously to be protective against Bordetella pertussis-induced hypersensitivity to histamine and anaphylaxis."}
{"id": "PMID:184132", "title": "Addition of fluoride to pit and fissure sealants--a feasibility study.", "content": "The data obtained in this in vitro study indicate that contact with pit and fissure sealants to which NaF has been added in amounts ranging from 2 to 5% substantially increases the fluoride content of the enamel and reduces its solubility in acid. The properties of the materials do not seem to be impaired by the addition of fluoride in these amounts. It thus appears that this approach to providing a backup anticariogenic mechanism may, indeed, be feasible. However, further investigation must be done to confirm the anticariogenic effect and to establish the most efficacious means of fluoride incorporation in the materials.", "contents": "Addition of fluoride to pit and fissure sealants--a feasibility study. The data obtained in this in vitro study indicate that contact with pit and fissure sealants to which NaF has been added in amounts ranging from 2 to 5% substantially increases the fluoride content of the enamel and reduces its solubility in acid. The properties of the materials do not seem to be impaired by the addition of fluoride in these amounts. It thus appears that this approach to providing a backup anticariogenic mechanism may, indeed, be feasible. However, further investigation must be done to confirm the anticariogenic effect and to establish the most efficacious means of fluoride incorporation in the materials."}
{"id": "PMID:184204", "title": "Peroxidase and fluorescein isothiocyanate as antibody markers. A quantitative comparison of two peroxidase conjugates prepared with glutaraldehyde or periodate anda fluorescein conjugate.", "content": "Batches of rabbit anti-human immunoglobulin G antibodies were labeled either with horseradish peroxidase, using the two-step glutaraldehyde method or the periodate method, or with fluorescein isothiocyanate (FITC). The peroxidase conjugates were isolated by chromatography using two different gel types. The five types of conjugates thus obtained were standardized to the same amount of rabbit immunoglobulin G. The antibody activity, as estimated by means of single radial immunodiffusion and passive hemagglutination, and the enzyme activity, determined with orthodianisidine, were compared. The ultimate dilutions and absolute amounts of the five conjugates giving positive reactions were determined in direct and indirect immunohistochemical tests, using both cryostat sections of skin and the agarose bead model system. It appeared that during the peroxidase conjugation procedures there was a considerable loss of abtibody and enzyme activity, whereas in the FITC conjugation procedure the antibody activity remained intact. Neverthe less, peroxidase conjugates prepared with glutaraldehyde still gave positive staining reactions in equal or somewhat higher dilutions than the fluorescin conjugate did. The peroxidase conjugates prepared with periodate could not be diluted to the same extent. For the detection of antibodies by indirect immunohistochemical methods, the peroxidase conjugate, prepared with glutaraldehyde, was comparable to the FITC conjugate. The peroxidase conjugate, prepared with periodate, was less effective.", "contents": "Peroxidase and fluorescein isothiocyanate as antibody markers. A quantitative comparison of two peroxidase conjugates prepared with glutaraldehyde or periodate anda fluorescein conjugate. Batches of rabbit anti-human immunoglobulin G antibodies were labeled either with horseradish peroxidase, using the two-step glutaraldehyde method or the periodate method, or with fluorescein isothiocyanate (FITC). The peroxidase conjugates were isolated by chromatography using two different gel types. The five types of conjugates thus obtained were standardized to the same amount of rabbit immunoglobulin G. The antibody activity, as estimated by means of single radial immunodiffusion and passive hemagglutination, and the enzyme activity, determined with orthodianisidine, were compared. The ultimate dilutions and absolute amounts of the five conjugates giving positive reactions were determined in direct and indirect immunohistochemical tests, using both cryostat sections of skin and the agarose bead model system. It appeared that during the peroxidase conjugation procedures there was a considerable loss of abtibody and enzyme activity, whereas in the FITC conjugation procedure the antibody activity remained intact. Neverthe less, peroxidase conjugates prepared with glutaraldehyde still gave positive staining reactions in equal or somewhat higher dilutions than the fluorescin conjugate did. The peroxidase conjugates prepared with periodate could not be diluted to the same extent. For the detection of antibodies by indirect immunohistochemical methods, the peroxidase conjugate, prepared with glutaraldehyde, was comparable to the FITC conjugate. The peroxidase conjugate, prepared with periodate, was less effective."}
{"id": "PMID:184205", "title": "Application of the fluorescent antibodies method for rapid diagnosis caused of diseases by pox viruses.", "content": "The results of application of the fluorescent antibodies method (MFA) with the diagnostic purpose of detecting pox antigen in specimens from smallpox patients are presented, The method was found highly effective for the examination of material taken directly from the patients (smears) in the early stages of disease (maculo-papular and vesicular). The results of examination of smears from pustular fluid and scabs were not reliable in 44% of cases due to the presence of nonspecific fluorescence of tissue fragments and leukocytes. The technique of preliminary accumulation of the virus in a sensitive cell culture made the MFA suitable for the examination of material taken at any stage of disease. Results of the assessment of sensitivity of MFA in comparison with other methods of rapid diagnosis of smallpox are presented.", "contents": "Application of the fluorescent antibodies method for rapid diagnosis caused of diseases by pox viruses. The results of application of the fluorescent antibodies method (MFA) with the diagnostic purpose of detecting pox antigen in specimens from smallpox patients are presented, The method was found highly effective for the examination of material taken directly from the patients (smears) in the early stages of disease (maculo-papular and vesicular). The results of examination of smears from pustular fluid and scabs were not reliable in 44% of cases due to the presence of nonspecific fluorescence of tissue fragments and leukocytes. The technique of preliminary accumulation of the virus in a sensitive cell culture made the MFA suitable for the examination of material taken at any stage of disease. Results of the assessment of sensitivity of MFA in comparison with other methods of rapid diagnosis of smallpox are presented."}
{"id": "PMID:184207", "title": "Application of the fluorescent antibodies method for rapid diagnosis caused of diseases by pox viruses.", "content": "The results of application of the fluorescent antibodies method (MFA) with the diagnostic purpose of detecting pox antigen in specimens from smallpox patients are presented. The method was found highly effective for the examination of material taken directly from the patients (smears) in the early stages of disease (maculo-papular and vesicular). The results of examination of smears from pustular fluid and scabs were not reliable in 44% of cases due to the presence of nonspecific fluorescence of tissue fragments and leukocytes. The technique of preliminary accumulation of the virus in a sensitive cell culture made the MFA suitable for the examination of material taken at any stage of disease. Results of the assessment of sensitivity of MFA in comparison with other methods of rapid diagnosis of smallpox are presented.", "contents": "Application of the fluorescent antibodies method for rapid diagnosis caused of diseases by pox viruses. The results of application of the fluorescent antibodies method (MFA) with the diagnostic purpose of detecting pox antigen in specimens from smallpox patients are presented. The method was found highly effective for the examination of material taken directly from the patients (smears) in the early stages of disease (maculo-papular and vesicular). The results of examination of smears from pustular fluid and scabs were not reliable in 44% of cases due to the presence of nonspecific fluorescence of tissue fragments and leukocytes. The technique of preliminary accumulation of the virus in a sensitive cell culture made the MFA suitable for the examination of material taken at any stage of disease. Results of the assessment of sensitivity of MFA in comparison with other methods of rapid diagnosis of smallpox are presented."}
{"id": "PMID:184208", "title": "Surveillance of pertussis in the CSSR. IV. Immunological surveys of antibodies to pertussis and parapertussis in the Bohemian regions and in Slovakia in 1958 - 1971.", "content": "A comparison of the results of repeated immunological surveys with the notification of morbidity and mortality to pertussis and parapertussis revealed direct dependence and simultaneously confirmed the effectiveness of Czechoslovak vaccine. Immunological surveys should be continued in spite of the fact that morbidity of pertussis is low at present, because immunological surveys may lead to timely detection of shortcomings in the quality of vaccination and vaccine. The results after 14 years of systematic vaccination and revaccination and consequent follow-up to the state of immunity in the population and of other factors in the pertussis surveillance programme rank among the other achievements of epidemiology and hygiene in Czechoslovak health services. Contemporary immunological surveys show that the state of immunity in Czechoslovak child population is such as to exclude the occurrence of pertussis in epidemics in the nearest future. The situation is different in parapertussis where epidemic incidence is still possible and where epidemics regularly occur in children of prae-school age.", "contents": "Surveillance of pertussis in the CSSR. IV. Immunological surveys of antibodies to pertussis and parapertussis in the Bohemian regions and in Slovakia in 1958 - 1971. A comparison of the results of repeated immunological surveys with the notification of morbidity and mortality to pertussis and parapertussis revealed direct dependence and simultaneously confirmed the effectiveness of Czechoslovak vaccine. Immunological surveys should be continued in spite of the fact that morbidity of pertussis is low at present, because immunological surveys may lead to timely detection of shortcomings in the quality of vaccination and vaccine. The results after 14 years of systematic vaccination and revaccination and consequent follow-up to the state of immunity in the population and of other factors in the pertussis surveillance programme rank among the other achievements of epidemiology and hygiene in Czechoslovak health services. Contemporary immunological surveys show that the state of immunity in Czechoslovak child population is such as to exclude the occurrence of pertussis in epidemics in the nearest future. The situation is different in parapertussis where epidemic incidence is still possible and where epidemics regularly occur in children of prae-school age."}
{"id": "PMID:184212", "title": "Melanocyte-stimulating hormone receptors on cultured guinea-pig melanocytes.", "content": "Guinea-pig melanocytes in mixed epidermal cell cultures bind melanocyte-stimulating hormone in a distinct focal surface area in their perinuclear field and thus follow the same pattern previously described for Cloudman melanoma cells. The labeling index ranged from 18 to 34%. Pretreatment of cultures with trypsin leads to destruction of melanocyte-stimulating hormone receptors whereas neuraminidase has no such effect.", "contents": "Melanocyte-stimulating hormone receptors on cultured guinea-pig melanocytes. Guinea-pig melanocytes in mixed epidermal cell cultures bind melanocyte-stimulating hormone in a distinct focal surface area in their perinuclear field and thus follow the same pattern previously described for Cloudman melanoma cells. The labeling index ranged from 18 to 34%. Pretreatment of cultures with trypsin leads to destruction of melanocyte-stimulating hormone receptors whereas neuraminidase has no such effect."}
{"id": "PMID:184213", "title": "Susceptibility of \"enterobacteria\" to aminoglycoside antibiotics: comparisons with tetracyclines, polymyxins, chloramphenicol, and spectinomycin.", "content": "Strains of enterobacteria, including common, aerobic, pathogenic gram-negative bacilli, and enterococci were tested for susceptibility to 11 aminoglycoside antibiotics by a twofold agar-dilution method with an inocula replicator. For comparison, similar tests were done with seven tetracycline analogues, two polymyxins, chloramphenicol, and spectinomycin. Tobramycin compared favorably with the more active aminoglycosides, with some exceptions related to individual strains of species. The tetracyclines and chloramphenicol were generally less active than the more active aminoglycosides. The polymyxins were as active or more active against most species of gram-negative rods but were essentially inactive against Proteus, Providencia, and many strains of Enterobacter.", "contents": "Susceptibility of \"enterobacteria\" to aminoglycoside antibiotics: comparisons with tetracyclines, polymyxins, chloramphenicol, and spectinomycin. Strains of enterobacteria, including common, aerobic, pathogenic gram-negative bacilli, and enterococci were tested for susceptibility to 11 aminoglycoside antibiotics by a twofold agar-dilution method with an inocula replicator. For comparison, similar tests were done with seven tetracycline analogues, two polymyxins, chloramphenicol, and spectinomycin. Tobramycin compared favorably with the more active aminoglycosides, with some exceptions related to individual strains of species. The tetracyclines and chloramphenicol were generally less active than the more active aminoglycosides. The polymyxins were as active or more active against most species of gram-negative rods but were essentially inactive against Proteus, Providencia, and many strains of Enterobacter."}
{"id": "PMID:184218", "title": "A possible role for cyclic nucleotides in the regulation of erythrocyte shape and permeability.", "content": "Erythrocytes treated with vinblastine or colchicine become spheroidal, more permeable to sodium, and of diminished deformability; upon reinjection they are rapidly sequestered and destroyed in the spleen. These deleterious effects are competitively inhibited by the cyclic nucleotides, guanosine 3',5'-monophosphate or adenosine 3',5'-monophosphate. The data suggest that cyclic nucleotides may be involved in normal erythrocyte shape and survival by interacting with membrane components that also react with vinblastine and colchicine. Similar interactions have been noted previously in diverse proliferating cells as well.", "contents": "A possible role for cyclic nucleotides in the regulation of erythrocyte shape and permeability. Erythrocytes treated with vinblastine or colchicine become spheroidal, more permeable to sodium, and of diminished deformability; upon reinjection they are rapidly sequestered and destroyed in the spleen. These deleterious effects are competitively inhibited by the cyclic nucleotides, guanosine 3',5'-monophosphate or adenosine 3',5'-monophosphate. The data suggest that cyclic nucleotides may be involved in normal erythrocyte shape and survival by interacting with membrane components that also react with vinblastine and colchicine. Similar interactions have been noted previously in diverse proliferating cells as well."}
{"id": "PMID:184219", "title": "Cyclic AMP and bicarbonate responses of the dog pancreas to vasoactive intestinal peptide (VIP) and secretion.", "content": "The effects of secretin (3 CU per kilogram) and vasoactive intestinal peptide (VIP; 8 mug per kilogram) on bicarbonate and cyclic AMP secretions in pancreatic juice (with pancreatic duct perfusion) and on pancreatic tissue cyclic AMP were investigated as a function of time in 13 anesthetized dogs. The peptides were given by rapid intravenous injection. Even 30 sec. after peptide administration, tissue cyclic AMP levels were elevated, reaching peak values within the first minute and a second peak at about 3 min. Bicarbonate and cyclic AMP secretions in pancreatic juice started with a lag of 1 min. after peptide injection. Following the injection of VIP, peak pancreatic response developed within the first 5 min. and the pancreatic response actually disappeared after 15 min., whereas secretion evoked by secretin was sustained for at least 30 min. The mean +/- S.D. observed maximal bicarbonate response to VIP (100 +/- 49 muEq./5 min.) was about one sixth of the maximum output following secretin (592 +/- 181 muEq./5 min.). Increases in pancreatic tissue and juice cyclic AMP caused by VIP were significant (p less than 0.05) at 1 and 4 min.; however, they were but moderate if compared with the rise achieved by secretin. The results presented confirm previous reports that VIP is a secretin-like partial agonist of pancreatic bicarbonate secretion and are compatible with the hypothesis that both secretin and VIP elicit canine pancreatic bicarbonate secretion via the second messenger system of cyclic AMP.", "contents": "Cyclic AMP and bicarbonate responses of the dog pancreas to vasoactive intestinal peptide (VIP) and secretion. The effects of secretin (3 CU per kilogram) and vasoactive intestinal peptide (VIP; 8 mug per kilogram) on bicarbonate and cyclic AMP secretions in pancreatic juice (with pancreatic duct perfusion) and on pancreatic tissue cyclic AMP were investigated as a function of time in 13 anesthetized dogs. The peptides were given by rapid intravenous injection. Even 30 sec. after peptide administration, tissue cyclic AMP levels were elevated, reaching peak values within the first minute and a second peak at about 3 min. Bicarbonate and cyclic AMP secretions in pancreatic juice started with a lag of 1 min. after peptide injection. Following the injection of VIP, peak pancreatic response developed within the first 5 min. and the pancreatic response actually disappeared after 15 min., whereas secretion evoked by secretin was sustained for at least 30 min. The mean +/- S.D. observed maximal bicarbonate response to VIP (100 +/- 49 muEq./5 min.) was about one sixth of the maximum output following secretin (592 +/- 181 muEq./5 min.). Increases in pancreatic tissue and juice cyclic AMP caused by VIP were significant (p less than 0.05) at 1 and 4 min.; however, they were but moderate if compared with the rise achieved by secretin. The results presented confirm previous reports that VIP is a secretin-like partial agonist of pancreatic bicarbonate secretion and are compatible with the hypothesis that both secretin and VIP elicit canine pancreatic bicarbonate secretion via the second messenger system of cyclic AMP."}
{"id": "PMID:184220", "title": "The transport of esterified cholesterol in plasma high density lipoproteins of human subjects: a mathematical model.", "content": "The pattern of labeling of free and esterified cholesterol in the plasma high-density lipoproteins after an intravenous injection of [3H]-mevalonic acid has been examined in six human subjects with a variety of plasma lipoprotein phenotypes. Attempts have been made to fit these data to theoretical models of high-density lipoprotein esterified cholesterol transport constructed on the basis of previous experimental observation. The first model, which assumed that the high-density lipoprotein esterified cholesterol transport constructed on the basis of previous experimental observation. The first model, which assumed that the high-density lipoprotein esterified cholesterol comprised a single homogeneous pool, was incompatible with the observed data. The second model assumed a two-pool model in which all of the plasma esterified cholesterol was produced in a small, rapidly turning over subfraction of the high-density lipoproteins. From this pool it was assumed that esterified cholesterol was transferred to other lipoprotein fractions, including transfer to a larger and much more slowly turning over subfraction of the high density lipoproteins. The second model was quite compatible with the observed data. Furthermore, the calculated net transport of esterified cholesterol through the fast turning over pool was in a range similar to that reported elsewhere for whole plasma. It has been concluded that the two-pool model not only fits the experimental data, but also accords well with previously documented observations of plasma esterified cholesterol transport.", "contents": "The transport of esterified cholesterol in plasma high density lipoproteins of human subjects: a mathematical model. The pattern of labeling of free and esterified cholesterol in the plasma high-density lipoproteins after an intravenous injection of [3H]-mevalonic acid has been examined in six human subjects with a variety of plasma lipoprotein phenotypes. Attempts have been made to fit these data to theoretical models of high-density lipoprotein esterified cholesterol transport constructed on the basis of previous experimental observation. The first model, which assumed that the high-density lipoprotein esterified cholesterol transport constructed on the basis of previous experimental observation. The first model, which assumed that the high-density lipoprotein esterified cholesterol comprised a single homogeneous pool, was incompatible with the observed data. The second model assumed a two-pool model in which all of the plasma esterified cholesterol was produced in a small, rapidly turning over subfraction of the high-density lipoproteins. From this pool it was assumed that esterified cholesterol was transferred to other lipoprotein fractions, including transfer to a larger and much more slowly turning over subfraction of the high density lipoproteins. The second model was quite compatible with the observed data. Furthermore, the calculated net transport of esterified cholesterol through the fast turning over pool was in a range similar to that reported elsewhere for whole plasma. It has been concluded that the two-pool model not only fits the experimental data, but also accords well with previously documented observations of plasma esterified cholesterol transport."}
{"id": "PMID:184221", "title": "Low density and high density lipoprotein turnover following portacaval shunt in swine.", "content": "Turnover of 125I-low density lipoprotein (LDL) and of 131I-high density lipoprotein (HDL) was determined before and after end-to-side portacaval shunt in eight swine. LDL (d 1.019-1.063) and HDL (d.1.09-1.21) were isolated by ultracentrifugation and iodinated by the iodine monochloride technique. Immediately postoperatively there was no consistent change in the fractional catabolic rate (FCR) of LDL compared to preoperative control values, while in all animals FCR of HDL was significantly increased (by as much as 300%). After recovery from surgery, neither LDL nor HDL catabolic rates were significantly elevated above control values in four swine. However, plasma levels of LDL and HDL protein, and of LDL and HDL cholesterol were significantly reduced 10-12 weeks after the portacaval shunt. The reduced levels of LDL and HDL associated with normal fractional clearance rates imply a reduction in synthesis of LDL and HDL following portal diversion.", "contents": "Low density and high density lipoprotein turnover following portacaval shunt in swine. Turnover of 125I-low density lipoprotein (LDL) and of 131I-high density lipoprotein (HDL) was determined before and after end-to-side portacaval shunt in eight swine. LDL (d 1.019-1.063) and HDL (d.1.09-1.21) were isolated by ultracentrifugation and iodinated by the iodine monochloride technique. Immediately postoperatively there was no consistent change in the fractional catabolic rate (FCR) of LDL compared to preoperative control values, while in all animals FCR of HDL was significantly increased (by as much as 300%). After recovery from surgery, neither LDL nor HDL catabolic rates were significantly elevated above control values in four swine. However, plasma levels of LDL and HDL protein, and of LDL and HDL cholesterol were significantly reduced 10-12 weeks after the portacaval shunt. The reduced levels of LDL and HDL associated with normal fractional clearance rates imply a reduction in synthesis of LDL and HDL following portal diversion."}
{"id": "PMID:184222", "title": "Effect of essential fatty acid deficiency on the lipid composition of the Yoshida ascites hepatoma (AH 130) and of the liver and blood plasma from host and normal rats.", "content": "In order to study the response of a poorly differentiated tumor to nutritional manipulation, the Yoshida ascites hepatoma (AH 130) was grown in rats fed an essential fatty acid (EFA)-deficient diet and in rats fed a control diet. Hepatomas, livers, and blood plasma from host rats and normal rats were studied as to the effects of EFA deficiency on the lipid composition. Normal rats fed an EFA-deficient diet showed an increased concentration of triglycerides and cholesteryl esters in the liver and a reduced level of total phospholipids in plasma. Host rats fed the EFA-deficient diet showed a lower concentration of triglycerides in the liver when compared with the host rats fed a control diet. In addition, EFA-deficient host rats had reduced levels of plasma free fatty acids and triglycerides. These latter were markedly high in host rats under normal dietetic conditions. As compared to the livers of either host rats or normal rats fed the control diet, the Yoshida hepatoma cells had a lower content of total phospholipids and free fatty acids as well as a higher level of free cholesterol; they also showed a typical fatty acid pattern in their phospholipids. The main characteristics of this pattern were a high content of oleic and palmitoleic acids and a low level of C20 and C22 polyunsaturated fatty acids. Exposure of Yoshida hepatoma cells to an EFA-deficient environment resulted in a decrease in the concentration of total phospholipids and free fatty acids and in changes in the fatty acid composition similar to those observed in the livers of normal and host rats. These changes suggest that, under the experimental conditions used, the Yoshida hepatoma cells are responsive to EFA deficiency.", "contents": "Effect of essential fatty acid deficiency on the lipid composition of the Yoshida ascites hepatoma (AH 130) and of the liver and blood plasma from host and normal rats. In order to study the response of a poorly differentiated tumor to nutritional manipulation, the Yoshida ascites hepatoma (AH 130) was grown in rats fed an essential fatty acid (EFA)-deficient diet and in rats fed a control diet. Hepatomas, livers, and blood plasma from host rats and normal rats were studied as to the effects of EFA deficiency on the lipid composition. Normal rats fed an EFA-deficient diet showed an increased concentration of triglycerides and cholesteryl esters in the liver and a reduced level of total phospholipids in plasma. Host rats fed the EFA-deficient diet showed a lower concentration of triglycerides in the liver when compared with the host rats fed a control diet. In addition, EFA-deficient host rats had reduced levels of plasma free fatty acids and triglycerides. These latter were markedly high in host rats under normal dietetic conditions. As compared to the livers of either host rats or normal rats fed the control diet, the Yoshida hepatoma cells had a lower content of total phospholipids and free fatty acids as well as a higher level of free cholesterol; they also showed a typical fatty acid pattern in their phospholipids. The main characteristics of this pattern were a high content of oleic and palmitoleic acids and a low level of C20 and C22 polyunsaturated fatty acids. Exposure of Yoshida hepatoma cells to an EFA-deficient environment resulted in a decrease in the concentration of total phospholipids and free fatty acids and in changes in the fatty acid composition similar to those observed in the livers of normal and host rats. These changes suggest that, under the experimental conditions used, the Yoshida hepatoma cells are responsive to EFA deficiency."}
{"id": "PMID:184223", "title": "Studies on the transport of vitamin D and of 25-hydroxyvitamin D in human plasma.", "content": "A study was conducted to investigate whether human plasma contains one or more than one protein for the transport of vitamin D and of 25-hydroxyvitamin D (25-OH-D). Serum was labeled in vivo with a mixture of radioactive vitamin D3 (derived from orally administered tracer vitamin D3) and of endogenously synthesized labeled 25-OH-D3. Samples of such serum were subjected to several different protein fractionation procedures. Only a single peak of protein-bound radioactivity was observed after each of these procedures. The fraction comprising the ascending and the descending limbs of the single peak of protein-bound radioactivity (after each procedure) were separately pooled. In each instance the ratio of radioactive 25-OH-D3 to radioactive vitamin D3 was found to be almost identical in both the ascending and the descending limbs. Taken together, these findings provide strong evidence that human serum contains only a single binding protein responsible for the normal transport of both vitamin D and 25-OH-D. Plasma labeled in vitro with added 3H-labeled 25-OH-D3 was subjected to gel filtration on Sephadex G-200 and to chromatography on columns of DEAE-cellulose and of SP-Sephadex. After each of these procedures a single peak of protein-bound radioactivity was observed, with elution profiles of protein and of radioactivity that were identical with those observed with in vivo labeled serum. These data indicate that tracer 25-OH-D3 added to plasma in vitro binds to the same plasma protein normally responsible for the transport of vitamin D and of 25-OH-D.", "contents": "Studies on the transport of vitamin D and of 25-hydroxyvitamin D in human plasma. A study was conducted to investigate whether human plasma contains one or more than one protein for the transport of vitamin D and of 25-hydroxyvitamin D (25-OH-D). Serum was labeled in vivo with a mixture of radioactive vitamin D3 (derived from orally administered tracer vitamin D3) and of endogenously synthesized labeled 25-OH-D3. Samples of such serum were subjected to several different protein fractionation procedures. Only a single peak of protein-bound radioactivity was observed after each of these procedures. The fraction comprising the ascending and the descending limbs of the single peak of protein-bound radioactivity (after each procedure) were separately pooled. In each instance the ratio of radioactive 25-OH-D3 to radioactive vitamin D3 was found to be almost identical in both the ascending and the descending limbs. Taken together, these findings provide strong evidence that human serum contains only a single binding protein responsible for the normal transport of both vitamin D and 25-OH-D. Plasma labeled in vitro with added 3H-labeled 25-OH-D3 was subjected to gel filtration on Sephadex G-200 and to chromatography on columns of DEAE-cellulose and of SP-Sephadex. After each of these procedures a single peak of protein-bound radioactivity was observed, with elution profiles of protein and of radioactivity that were identical with those observed with in vivo labeled serum. These data indicate that tracer 25-OH-D3 added to plasma in vitro binds to the same plasma protein normally responsible for the transport of vitamin D and of 25-OH-D."}
{"id": "PMID:184224", "title": "Effect of an anti-lipoprotein lipase serum on plasma triglyceride removal.", "content": "Anti-lipoprotein lipase sera injected intravenously in roosters blocked quantitatively the catabolism of very low density lipoprotein (VLDL) triglyceride. Antibodies were produced in rabbits immunized with highly purified lipoprotein lipase (LPL, glycerol ester hydrolase, E C 3.1.1.3) prepared from chicken adipose tissue. Following anti-LPL serum injection there was a linear increase in plasma triglyceride concentration. The rate of entry of triglyceride in plasma was estimated from the rate of triglyceride accumulation in the plasma of animals injected with anti-LPL serum, or from the disappearance curve of biologically labelled VLDL. In instances where both measurements were conducted in the same animals there was very close agreement between the two procedures. Inhibition of VLDL triglyceride catabolism of anti-LPL serum provided a way to characterize newly secreted VLDL that exhibited a broad spectrum of particle sizes with a median of 625 A degrees. They contained 76.2 +/- 1.2% triglyceride and had a high ratio of free to ester cholesterol (2.46 +/- 0.45). In control VLDL samples there was 46.1% triglyceride, and the ratio of free to ester cholesterol was 1.19. The complete inhibition of triglyceride removal by an antiserum prepared against adipose tissue LPL demonstrates that the NaCl-inhibited, serum-activated lipase prepared by affinity chromatography on heparin-Sepharose and concanavalin A-Sepharose columns is the enzyme responsible in vivo for the catabolism of VLDL triglyceride. Further, the kinetics of triglyceride accumulation in the plasma provide evidence that the site of degradation of VLDL triglyceride is within the plasma compartment.", "contents": "Effect of an anti-lipoprotein lipase serum on plasma triglyceride removal. Anti-lipoprotein lipase sera injected intravenously in roosters blocked quantitatively the catabolism of very low density lipoprotein (VLDL) triglyceride. Antibodies were produced in rabbits immunized with highly purified lipoprotein lipase (LPL, glycerol ester hydrolase, E C 3.1.1.3) prepared from chicken adipose tissue. Following anti-LPL serum injection there was a linear increase in plasma triglyceride concentration. The rate of entry of triglyceride in plasma was estimated from the rate of triglyceride accumulation in the plasma of animals injected with anti-LPL serum, or from the disappearance curve of biologically labelled VLDL. In instances where both measurements were conducted in the same animals there was very close agreement between the two procedures. Inhibition of VLDL triglyceride catabolism of anti-LPL serum provided a way to characterize newly secreted VLDL that exhibited a broad spectrum of particle sizes with a median of 625 A degrees. They contained 76.2 +/- 1.2% triglyceride and had a high ratio of free to ester cholesterol (2.46 +/- 0.45). In control VLDL samples there was 46.1% triglyceride, and the ratio of free to ester cholesterol was 1.19. The complete inhibition of triglyceride removal by an antiserum prepared against adipose tissue LPL demonstrates that the NaCl-inhibited, serum-activated lipase prepared by affinity chromatography on heparin-Sepharose and concanavalin A-Sepharose columns is the enzyme responsible in vivo for the catabolism of VLDL triglyceride. Further, the kinetics of triglyceride accumulation in the plasma provide evidence that the site of degradation of VLDL triglyceride is within the plasma compartment."}
{"id": "PMID:184228", "title": "Incorporation of 14C-labelled amino acids into corticotrophin-like intermediate lobe peptide and alpha-melanocyte-stimulating hormone by the rat pituitary neurointermediate lobe in vitro, and the identification of four new pars intermedia peptides.", "content": "At least seven radioactive peptides, which fractionated on Biogel P6, were found in rat neurointermediate lobes after incubation for 6 h with [14C]proline. Only three of these could be tentatively identified; one as alpha-melanocyte-stimulating hormone (alpha-MSH) and two as forms of corticotrophin-like intermediate lobe peptide (CLIP). One other cross-reacted partially with a beta-malanocyte-stimulating hormone (beta-MSH) antiserum, was acidically charged and eluted on Biogel P6 in roughly the same position as ACTH. The other three peptides showed no resemblance to alpha-MSH, CLIP, beta-MSH or ACTH.", "contents": "Incorporation of 14C-labelled amino acids into corticotrophin-like intermediate lobe peptide and alpha-melanocyte-stimulating hormone by the rat pituitary neurointermediate lobe in vitro, and the identification of four new pars intermedia peptides. At least seven radioactive peptides, which fractionated on Biogel P6, were found in rat neurointermediate lobes after incubation for 6 h with [14C]proline. Only three of these could be tentatively identified; one as alpha-melanocyte-stimulating hormone (alpha-MSH) and two as forms of corticotrophin-like intermediate lobe peptide (CLIP). One other cross-reacted partially with a beta-malanocyte-stimulating hormone (beta-MSH) antiserum, was acidically charged and eluted on Biogel P6 in roughly the same position as ACTH. The other three peptides showed no resemblance to alpha-MSH, CLIP, beta-MSH or ACTH."}
{"id": "PMID:184229", "title": "Effects of corticosterone on adrenocorticotrophin-induced mitochondrial differentiation with special reference to 11 beta- and 18-hydroxylation.", "content": "The effects of corticosterone in concentrations found in adrenal venous plasma on ACTH-induced changes in cultured cortical cells derived from foetal rat adrenals were studied. Corticosterone at a concentration of 5-7 X 10(-5) mol/l completely inhibited mitochondrial differentiation to fasciculte-like morphology. The same cultures revealed significant inhibition of 11beta- and 18-hydroxylation compared with cultures treated with ACTH only. This was shown by the reduced formation of corticosterone and 18-OH-deoxycorticosterone (48%, P less than 0-001) and simultaneous enhancement of deoxycorticosterone formation (33%, P less than 0-05) from added [4-14C]progesterone. Similar inhibition was observed when dibutyryl cyclic AMP replaced ACTH as an inducer of differentiation. Lower concentrations of corticosterone (1-2 X 10(-5) and 2-4 X 10(-5) mol/l) inhibited ACTH-stimulated formation of corticosterone and 18-OH-deoxycorticosterone from endogenous precursors. The results demonstrate that corticosterone regulates the stage of differentiation in cultured adrenocortical cells. The possible role of corticosterone in the regulation of growth and steroidogenic capacity of the adrenal cortex is discussed.", "contents": "Effects of corticosterone on adrenocorticotrophin-induced mitochondrial differentiation with special reference to 11 beta- and 18-hydroxylation. The effects of corticosterone in concentrations found in adrenal venous plasma on ACTH-induced changes in cultured cortical cells derived from foetal rat adrenals were studied. Corticosterone at a concentration of 5-7 X 10(-5) mol/l completely inhibited mitochondrial differentiation to fasciculte-like morphology. The same cultures revealed significant inhibition of 11beta- and 18-hydroxylation compared with cultures treated with ACTH only. This was shown by the reduced formation of corticosterone and 18-OH-deoxycorticosterone (48%, P less than 0-001) and simultaneous enhancement of deoxycorticosterone formation (33%, P less than 0-05) from added [4-14C]progesterone. Similar inhibition was observed when dibutyryl cyclic AMP replaced ACTH as an inducer of differentiation. Lower concentrations of corticosterone (1-2 X 10(-5) and 2-4 X 10(-5) mol/l) inhibited ACTH-stimulated formation of corticosterone and 18-OH-deoxycorticosterone from endogenous precursors. The results demonstrate that corticosterone regulates the stage of differentiation in cultured adrenocortical cells. The possible role of corticosterone in the regulation of growth and steroidogenic capacity of the adrenal cortex is discussed."}
{"id": "PMID:184230", "title": "Effects of follicle-stimulating hormone and luteinizing hormone on ovarian cyclic AMP and prostaglandin E in vivo in rats treated with indomethacin.", "content": "The role of prostaglandins in both FSH- and LH-mediated increases in ovarian cyclic AMP was examined in rats in vivo. Dose-related increases in ovarian cyclic AMP levels were observed 10 min after intravenous injection of FSH or LH. No changes in ovarian prostaglandin E (PGE) content were detected after injection of either gonadotrophin at doses which substantially enhanced cyclic AMP accumulation. Prior treatment of rats with indomethacin produced a greater than 50% decrease in ovarian PGE levels, but did not prevent the FSH- or LH-induced rise in ovarian cyclic AMP concentration. These in vivo experiments do not support the concept that PGE plays a role as an obligatory mediator for the gonadotrophin-induced rise in ovarian cyclic AMP levels.", "contents": "Effects of follicle-stimulating hormone and luteinizing hormone on ovarian cyclic AMP and prostaglandin E in vivo in rats treated with indomethacin. The role of prostaglandins in both FSH- and LH-mediated increases in ovarian cyclic AMP was examined in rats in vivo. Dose-related increases in ovarian cyclic AMP levels were observed 10 min after intravenous injection of FSH or LH. No changes in ovarian prostaglandin E (PGE) content were detected after injection of either gonadotrophin at doses which substantially enhanced cyclic AMP accumulation. Prior treatment of rats with indomethacin produced a greater than 50% decrease in ovarian PGE levels, but did not prevent the FSH- or LH-induced rise in ovarian cyclic AMP concentration. These in vivo experiments do not support the concept that PGE plays a role as an obligatory mediator for the gonadotrophin-induced rise in ovarian cyclic AMP levels."}
{"id": "PMID:184234", "title": "The development of a radioimmuno-assay for carcino-embryonic antigen with some applications. Clinical evaluation of carcino-embryonic antigen, I.", "content": "This paper, the first in a series devoted to the study of the clinical usefulness of estimations of carcino-embryonic antigen (CEA) in serum and urine, describes in detail a direct radioimmunoassay for CEA in serum and urine (a modified Egan technique, Egan, M.L. et al. (1972), Immunochemistry, 9, 289-299). A comparative study of the behaviour of CEA batches and anti-CEA antisera from different laboratories in the radioimmunoassay is presented. The incidence of increased serum CEA levels in healthy smokers was found to be related to smoking habits. Assays of CEA in serum obtained by the direct technique and the Hansen perchloric acid--zirconyl gel technique (Hansen, H.J. et al. (1971), Clin. Res. 19, 143-147) showed comparable results. Various problems affecting the assay of CEA in serum and urine are critically discussed, e.g. criteria for absorbing-out of anti-CEA antisera, identification of CEA, factors causing false CEA values, use of reference materials, acceptability of a strict cut-off level to indicate increased CEA levels, and factors governing the choice of antisera. In this connection we present a new approach which maintains a reliable and consistent cut-off level in follow-up studies. Evidence is presented that urinary CEA is heterogeneous and perchloric acid-unstable.", "contents": "The development of a radioimmuno-assay for carcino-embryonic antigen with some applications. Clinical evaluation of carcino-embryonic antigen, I. This paper, the first in a series devoted to the study of the clinical usefulness of estimations of carcino-embryonic antigen (CEA) in serum and urine, describes in detail a direct radioimmunoassay for CEA in serum and urine (a modified Egan technique, Egan, M.L. et al. (1972), Immunochemistry, 9, 289-299). A comparative study of the behaviour of CEA batches and anti-CEA antisera from different laboratories in the radioimmunoassay is presented. The incidence of increased serum CEA levels in healthy smokers was found to be related to smoking habits. Assays of CEA in serum obtained by the direct technique and the Hansen perchloric acid--zirconyl gel technique (Hansen, H.J. et al. (1971), Clin. Res. 19, 143-147) showed comparable results. Various problems affecting the assay of CEA in serum and urine are critically discussed, e.g. criteria for absorbing-out of anti-CEA antisera, identification of CEA, factors causing false CEA values, use of reference materials, acceptability of a strict cut-off level to indicate increased CEA levels, and factors governing the choice of antisera. In this connection we present a new approach which maintains a reliable and consistent cut-off level in follow-up studies. Evidence is presented that urinary CEA is heterogeneous and perchloric acid-unstable."}
{"id": "PMID:184235", "title": "The application of differential thermal analysis and thermogravimetric analysis to dating bone remains.", "content": "Thirty-four samples of bone remains of known time since death were studied by using DTA, TGA, and derivative-TGA techniques. The DTA patterns enable us to distinguish recent from old (more than 100 years) bones. The TGA curve is also significant for an extreme series. Both DTA and TGA curves show a correlation that allows us to obtain patterns with high significance for the extreme series. They also make evident the decomposition grade that bone organic material undergoes during the postmortem putrefactive process.", "contents": "The application of differential thermal analysis and thermogravimetric analysis to dating bone remains. Thirty-four samples of bone remains of known time since death were studied by using DTA, TGA, and derivative-TGA techniques. The DTA patterns enable us to distinguish recent from old (more than 100 years) bones. The TGA curve is also significant for an extreme series. Both DTA and TGA curves show a correlation that allows us to obtain patterns with high significance for the extreme series. They also make evident the decomposition grade that bone organic material undergoes during the postmortem putrefactive process."}
{"id": "PMID:184238", "title": "Annealing and hybridization properties of herpes simplex virus type 1 DNA.", "content": "The hybridization properties of the herpes simplex virus type 1 (HSV) genome have been analysed. The DNA has a kinetic complexity of 1 X 10(-8). E. cole RNA polymerase was found to initiate synthesis at about 70 sites on the HSV DNA. The in vitro RNA product from this reaction was complementary to about 80% of the HSV genome. The RNA-DNA hybridization rate constant (Kh) was determined using conditions of both RNA excess and DNA excess. Using this rate constant one can analyse the content of HSV sequences in any RNA population.", "contents": "Annealing and hybridization properties of herpes simplex virus type 1 DNA. The hybridization properties of the herpes simplex virus type 1 (HSV) genome have been analysed. The DNA has a kinetic complexity of 1 X 10(-8). E. cole RNA polymerase was found to initiate synthesis at about 70 sites on the HSV DNA. The in vitro RNA product from this reaction was complementary to about 80% of the HSV genome. The RNA-DNA hybridization rate constant (Kh) was determined using conditions of both RNA excess and DNA excess. Using this rate constant one can analyse the content of HSV sequences in any RNA population."}
{"id": "PMID:184239", "title": "Genesis and maintenance of a persistent infection by canine distemper virus.", "content": "Vero cells were persistently infected with canine distemper virus by continuous undiluted passage of virus harvests. The cells were refractory to superinfection by both measles virus and canine distemper virus. These persistently infected cells produced and released into the medium a labile component which had a potent and selective inhibitory effect on the replication of canine distemper and measles virus. The inhibitory agent was not inactivated by u.v.-irradiation or sedimented by ultracentrifugation. Antisera against canine distemper virus or SSPE sera were able to block this inhibitory effect. We propose that these persistently infected cells produce an excess of a virus-induced regulatory protein.", "contents": "Genesis and maintenance of a persistent infection by canine distemper virus. Vero cells were persistently infected with canine distemper virus by continuous undiluted passage of virus harvests. The cells were refractory to superinfection by both measles virus and canine distemper virus. These persistently infected cells produced and released into the medium a labile component which had a potent and selective inhibitory effect on the replication of canine distemper and measles virus. The inhibitory agent was not inactivated by u.v.-irradiation or sedimented by ultracentrifugation. Antisera against canine distemper virus or SSPE sera were able to block this inhibitory effect. We propose that these persistently infected cells produce an excess of a virus-induced regulatory protein."}
{"id": "PMID:184240", "title": "Further studies in genetic resistance of fowl to RSV(RAV O): evidence for interaction between independently segregating tumour virus b and tumour virus e genes.", "content": "The segregation of resistant and susceptible phenotypes in response to infection by RSV(RAV 2), RSV(RAV 50) and RSV(RAV 0), of avian RNA tumour virus subgroups B, D and E, respectively, was analysed in several test-crosses using chickens from the RPRL line 7-2, HPRS-synthetic line E and the Reaseheath line C. The results were fully consistent with out view reported previously that the genes at the tve and tvb loci segregate independently and recombine under the Mendelian second law of independent assortment. The dominant susceptibility es gene is expressed phenotypically when associated with the dominant susceptibility bs gene, but its expression is suppressed when associated with two doses of the recessive br gene. Genetic causes such as lack of penetration, recessive epistasis, and/or complementary intereaction between the tvb and tve genes have been discussed to account for the modified phenotypic expression of brbreses cells, i.e. resistance to subgroup E virus. Also, as reported previously, it was observed in this study that the tvb genes control the cellular response to subgroup D virus.", "contents": "Further studies in genetic resistance of fowl to RSV(RAV O): evidence for interaction between independently segregating tumour virus b and tumour virus e genes. The segregation of resistant and susceptible phenotypes in response to infection by RSV(RAV 2), RSV(RAV 50) and RSV(RAV 0), of avian RNA tumour virus subgroups B, D and E, respectively, was analysed in several test-crosses using chickens from the RPRL line 7-2, HPRS-synthetic line E and the Reaseheath line C. The results were fully consistent with out view reported previously that the genes at the tve and tvb loci segregate independently and recombine under the Mendelian second law of independent assortment. The dominant susceptibility es gene is expressed phenotypically when associated with the dominant susceptibility bs gene, but its expression is suppressed when associated with two doses of the recessive br gene. Genetic causes such as lack of penetration, recessive epistasis, and/or complementary intereaction between the tvb and tve genes have been discussed to account for the modified phenotypic expression of brbreses cells, i.e. resistance to subgroup E virus. Also, as reported previously, it was observed in this study that the tvb genes control the cellular response to subgroup D virus."}
{"id": "PMID:184241", "title": "Epstein-Barr nuclear antigen (EBNA) carrying lymphocytes in human palatine tonsils.", "content": "The presence of Epstein-Barr virus (EBV) antigens in human palatine tonsilderived lymphocytes (TDL) was investigated using the indirect fluorescent antibody (FA) technique. The TDL were screened for the presence of EBV early antigen (EA), virus capsid antigen (VCA), and EBV nuclear antigen (EBNA). In 76% of the patients diagnosed as recurrent exudative tonsillitis, and in 33% diagnosed as recurrent tonsillitis and/or serous otitis media, EBNA was demonstrated in the purified TDLs. No EA- or VCA-producing cells were found in either the glass adsorbed or TDL cell preparations from all of the patients. These data suggest that in our patient sample, the tonsils may serve as a reservoir for EBV carrying lymphocytes and a basis for recurrent disease.", "contents": "Epstein-Barr nuclear antigen (EBNA) carrying lymphocytes in human palatine tonsils. The presence of Epstein-Barr virus (EBV) antigens in human palatine tonsilderived lymphocytes (TDL) was investigated using the indirect fluorescent antibody (FA) technique. The TDL were screened for the presence of EBV early antigen (EA), virus capsid antigen (VCA), and EBV nuclear antigen (EBNA). In 76% of the patients diagnosed as recurrent exudative tonsillitis, and in 33% diagnosed as recurrent tonsillitis and/or serous otitis media, EBNA was demonstrated in the purified TDLs. No EA- or VCA-producing cells were found in either the glass adsorbed or TDL cell preparations from all of the patients. These data suggest that in our patient sample, the tonsils may serve as a reservoir for EBV carrying lymphocytes and a basis for recurrent disease."}
{"id": "PMID:184242", "title": "Morphological observations on the replication of herpesvirus saimiri in monkey kidney cell cultures.", "content": "Owl and African green monkey kidney cell cultures have been infected with 1 p.f.u./cell of herpesvirus saimiri and sample cultures have been taken for examination by electron microscopy at 3 to 6 hourly intervals over a period of 7 days; the experiments were repeated several times. The peculiarly slow replication cycle of Herpesvirus saimiri has enabled distinct cytoplasmic and nuclear phases in virus maturation to be clearly distinguished; the overall fine structural features were similar in both cell types. Immature particles were first detected in the nucleus and cytoplasm 63 h after infection. Thereafter, abundant cytoplasmic immature particles matured by budding through cytoplasmic membranes until about 100 h, whereas nuclear immature particles budded through the inner nuclear membrane or intranuclear invaginations of it later, from about 100 h until cytolysis was complete at 160 h. Morphological differences were also observed between particles budding at cytoplasmic membranes and the nuclear envelope. At the former site the membrane overlying the bud showed an electron opaque thickening which imparted to the mature particle an asymmetrical appearance. Such thickenings of the envelope were not observed in mature particles of nuclear origin. Unusual tubular and laminated nuclear structures were seen towards the end of the replicative cycle corresponding with the phase of nuclear virus maturation by budding; the morphology of the latter structures is described.", "contents": "Morphological observations on the replication of herpesvirus saimiri in monkey kidney cell cultures. Owl and African green monkey kidney cell cultures have been infected with 1 p.f.u./cell of herpesvirus saimiri and sample cultures have been taken for examination by electron microscopy at 3 to 6 hourly intervals over a period of 7 days; the experiments were repeated several times. The peculiarly slow replication cycle of Herpesvirus saimiri has enabled distinct cytoplasmic and nuclear phases in virus maturation to be clearly distinguished; the overall fine structural features were similar in both cell types. Immature particles were first detected in the nucleus and cytoplasm 63 h after infection. Thereafter, abundant cytoplasmic immature particles matured by budding through cytoplasmic membranes until about 100 h, whereas nuclear immature particles budded through the inner nuclear membrane or intranuclear invaginations of it later, from about 100 h until cytolysis was complete at 160 h. Morphological differences were also observed between particles budding at cytoplasmic membranes and the nuclear envelope. At the former site the membrane overlying the bud showed an electron opaque thickening which imparted to the mature particle an asymmetrical appearance. Such thickenings of the envelope were not observed in mature particles of nuclear origin. Unusual tubular and laminated nuclear structures were seen towards the end of the replicative cycle corresponding with the phase of nuclear virus maturation by budding; the morphology of the latter structures is described."}
{"id": "PMID:184243", "title": "Virus specified enzyme activity and RNA species in herpes simplex virus type 1 transformed mouse cells.", "content": "LMTK-cells infected with u.v.-irradiated herpes simplex virus type 1 have been selected for the presence of the enzyme thymidine kinase. These cells have an altered morphology compared to the control cells and contain herpes-specific antigens in their cytoplasm. The thymidine kinase activity present in these cells has been shown, on the basis of a number of biochemical properties, to be identical to the herpes virus specified deoxypyrimidine kinase found during lytic infection of this virus. In addition it has been possible to detect herpes simplex-specific RNA sequences in the transformed cells and this occurs in both the polyadenylated and non-polyadenylated cytoplasmic and nuclear fractions.", "contents": "Virus specified enzyme activity and RNA species in herpes simplex virus type 1 transformed mouse cells. LMTK-cells infected with u.v.-irradiated herpes simplex virus type 1 have been selected for the presence of the enzyme thymidine kinase. These cells have an altered morphology compared to the control cells and contain herpes-specific antigens in their cytoplasm. The thymidine kinase activity present in these cells has been shown, on the basis of a number of biochemical properties, to be identical to the herpes virus specified deoxypyrimidine kinase found during lytic infection of this virus. In addition it has been possible to detect herpes simplex-specific RNA sequences in the transformed cells and this occurs in both the polyadenylated and non-polyadenylated cytoplasmic and nuclear fractions."}
{"id": "PMID:184256", "title": "Individual EPSPs produced by single triceps surae Ia afferent fibers in homonymous and heteronymous motoneurons.", "content": "1. The individual EPSPs evoked by the action of single Ia fibers from cat triceps surae (MG, LG, SOL) were recorded in homonymous and heteronymous motoneurons innervating these same three muscles. 2. In general, Ia fibers projected to a greater percentage of homonymous than heteronymous motoneurons. One class of Ia afferent evoked EPSPs in virtually all homonymous motoneurons; the other had a substantially lower projection frequency. Possible difficulties introduced by the limited resolution of the averaging technique are discussed. 3. Individual EPSPs were larger on the average if evoked a) in SOL rather than in MG or LG motoneurons, b) by LG rather than by MG or SOL afferent fibers, or c) in homonymous rather than in heteronymous motoneurons. The mean EPSP was larger in homonymous than in heteronymous motoneurons because the largest EPSPs (greater than 150 muV) were found mainly in homonymous motoneurons. 4. Rise times of EPSPs were only slightly shorter in homonymous than in heteronymous motoneurons, suggesting that other factors besides relative location of Ia terminals account for the observed EPSP amplitude differences. Rise times in SOL motoneurons were longer than those in MG or LG. 5. LG afferent fibers tended to produce larger EPSPs in rostral than in caudal LG motoneurons, and MG afferents produced larger EPSPs in caudal than in rostral MG motoneurons. These spatial effects were in accord with the more rostral entry of LG than MG Ia afferents into the spinal cord. The differential projection of SOL afferents to MG and SOL motoneurons which overlap spatially in the spinal cord suggests a species specificity in addition to a location specificity.", "contents": "Individual EPSPs produced by single triceps surae Ia afferent fibers in homonymous and heteronymous motoneurons. 1. The individual EPSPs evoked by the action of single Ia fibers from cat triceps surae (MG, LG, SOL) were recorded in homonymous and heteronymous motoneurons innervating these same three muscles. 2. In general, Ia fibers projected to a greater percentage of homonymous than heteronymous motoneurons. One class of Ia afferent evoked EPSPs in virtually all homonymous motoneurons; the other had a substantially lower projection frequency. Possible difficulties introduced by the limited resolution of the averaging technique are discussed. 3. Individual EPSPs were larger on the average if evoked a) in SOL rather than in MG or LG motoneurons, b) by LG rather than by MG or SOL afferent fibers, or c) in homonymous rather than in heteronymous motoneurons. The mean EPSP was larger in homonymous than in heteronymous motoneurons because the largest EPSPs (greater than 150 muV) were found mainly in homonymous motoneurons. 4. Rise times of EPSPs were only slightly shorter in homonymous than in heteronymous motoneurons, suggesting that other factors besides relative location of Ia terminals account for the observed EPSP amplitude differences. Rise times in SOL motoneurons were longer than those in MG or LG. 5. LG afferent fibers tended to produce larger EPSPs in rostral than in caudal LG motoneurons, and MG afferents produced larger EPSPs in caudal than in rostral MG motoneurons. These spatial effects were in accord with the more rostral entry of LG than MG Ia afferents into the spinal cord. The differential projection of SOL afferents to MG and SOL motoneurons which overlap spatially in the spinal cord suggests a species specificity in addition to a location specificity."}
{"id": "PMID:184257", "title": "Interaction of electrosensory and electromotor signals in lateral line lobe of a mormyrid fish.", "content": "A signal associated with the neural command to discharge the electric organ is recorded in cells of the lateral line lobe. Responses of cells activated by medium receptor inputs are facilitated or less frequently inhibited during this command-associated signal. Only responses to disynaptic inputs are affected, the monosynaptic response is not altered. The periods of facilitation and inhibition occur at times at which electroreceptor activity evoked by organ discharge reaches the lateral line lobe. Presumably the command-associated signal is important in electrolocation. Cells responding to large receptor inputs are inhibited by the command-associated signal. Activity evoked by large receptors is transmitted in a mesencephalic fiber tract. The tract response is also inhibited by the command-associated signal. Since each organ discharge would excite all the large receptors at short latency, there would be little information contained in their responses. Inhibiting discharge-evoked activity may allow the system to return to maximum sensitivity most rapidly.", "contents": "Interaction of electrosensory and electromotor signals in lateral line lobe of a mormyrid fish. A signal associated with the neural command to discharge the electric organ is recorded in cells of the lateral line lobe. Responses of cells activated by medium receptor inputs are facilitated or less frequently inhibited during this command-associated signal. Only responses to disynaptic inputs are affected, the monosynaptic response is not altered. The periods of facilitation and inhibition occur at times at which electroreceptor activity evoked by organ discharge reaches the lateral line lobe. Presumably the command-associated signal is important in electrolocation. Cells responding to large receptor inputs are inhibited by the command-associated signal. Activity evoked by large receptors is transmitted in a mesencephalic fiber tract. The tract response is also inhibited by the command-associated signal. Since each organ discharge would excite all the large receptors at short latency, there would be little information contained in their responses. Inhibiting discharge-evoked activity may allow the system to return to maximum sensitivity most rapidly."}
{"id": "PMID:184258", "title": "Pathologenesis of hematogenous bacterial meningitis in rabbits.", "content": "The authors present data obtained from a series of 27 rabbits studied following intracarotid injection of saline, brain-heart infusion broth, aerobic, or anaerobic bacteria. These data support the hypothesis that injections of cultures of both aerobic and anaerobic organisms by way of the carotid artery disrupts the blood-brain barrier over the cerebral convexities within 15 minutes; however, the inflammatory response and bacterial proliferation occur much more rapidly in the ventricular system. Within 3 hours,the barrier over the convexities is intact, but leukocytes and organisms may be seen in the long cilia of the aqeuductal region. A relative failure of leucotaxis over the convexities of the brain is the most likely explanation of these preliminary findings in this experimental model.", "contents": "Pathologenesis of hematogenous bacterial meningitis in rabbits. The authors present data obtained from a series of 27 rabbits studied following intracarotid injection of saline, brain-heart infusion broth, aerobic, or anaerobic bacteria. These data support the hypothesis that injections of cultures of both aerobic and anaerobic organisms by way of the carotid artery disrupts the blood-brain barrier over the cerebral convexities within 15 minutes; however, the inflammatory response and bacterial proliferation occur much more rapidly in the ventricular system. Within 3 hours,the barrier over the convexities is intact, but leukocytes and organisms may be seen in the long cilia of the aqeuductal region. A relative failure of leucotaxis over the convexities of the brain is the most likely explanation of these preliminary findings in this experimental model."}
{"id": "PMID:184259", "title": "Evaluation of radiopharmaceuticals sequestered by acutely damaged myocardium.", "content": "Eighteen radiopharmaceuticals were screened in a small-animal model as potential infarct-localizing agents. Twelve of the 18 compounds were labeled with 99mTc, four with 203Hg, one with 131I, and one with either 203Hg or 125I. The model used heat-induced myocardial lesions in the rat. The absolute concentration within the lesion and also the activity ratios of injured myocardium to normal heart tissue, blood, and muscle were determined for all compounds. Among the 99mTc-labeled agents, two bone-seekers [pyrophosphate (PPi) and 1-hydroxyethylidine-1,1-diphosphonate (HEDP)] showed the most promise; these were followed by 99mTc-tetracycline analogs and 99mTc-glucoheptonaate. The tracer showing the most favorable concentration in the lesion and the best target-to-nontarget ratios was an iodinated derivatives of hydroxymercurifluorescein labeled with either 125I or 203Hg. Consideration of the structure of these compounds suggests that the presence of mercury or of a polycyclic aromatic structure, such as that found is tetracycline and fluorescein, was associated with localization in damaged myocardial tissue. Mercury bound to such an aromatic moiety may produce an additive or even a synergistic effect.", "contents": "Evaluation of radiopharmaceuticals sequestered by acutely damaged myocardium. Eighteen radiopharmaceuticals were screened in a small-animal model as potential infarct-localizing agents. Twelve of the 18 compounds were labeled with 99mTc, four with 203Hg, one with 131I, and one with either 203Hg or 125I. The model used heat-induced myocardial lesions in the rat. The absolute concentration within the lesion and also the activity ratios of injured myocardium to normal heart tissue, blood, and muscle were determined for all compounds. Among the 99mTc-labeled agents, two bone-seekers [pyrophosphate (PPi) and 1-hydroxyethylidine-1,1-diphosphonate (HEDP)] showed the most promise; these were followed by 99mTc-tetracycline analogs and 99mTc-glucoheptonaate. The tracer showing the most favorable concentration in the lesion and the best target-to-nontarget ratios was an iodinated derivatives of hydroxymercurifluorescein labeled with either 125I or 203Hg. Consideration of the structure of these compounds suggests that the presence of mercury or of a polycyclic aromatic structure, such as that found is tetracycline and fluorescein, was associated with localization in damaged myocardial tissue. Mercury bound to such an aromatic moiety may produce an additive or even a synergistic effect."}
{"id": "PMID:184260", "title": "alpha-Aminoisobutyric acid transport in liver slices from rats fed low protein meals.", "content": "The effect of low protein intake on alpha-aminioisobutyric acid (AIB) transport has been examined in liver slices from meal-fed rats. Treatments (force-feeding casein or gelatin hydrolysates, glycine, or potassium chloride; injecting glucagon, or preincubating liver slices with cyclic AMP) which stimulated transport in control rat fed 3-hour meals containing 18% casein were less effective in rats fed 6% casein meals for 8 days. Responses of protein-depleted rats to glucagon or cyclic AMP had become essentially normal after they had consumed 18% casein meals for 2 days, whereas between 6 to 10 days were required for complete recovery of the response to casein hydrolysate. Stimulation of AIB transport by casein hydrolysate was also normal in depleted rats after they had consumed 40% casein meals for 2 days. Basal, non-stimulated transport of AIB was not significantly depressed in rats fed the low protein diet. Casein hydrolysate-induced increases in hepatic cyclic AMP concentrations were smaller in rats fed low protein meals. The results show that, although various stimuli of hepatic AIB transport become less effective in the protein-deprived rat, relatively rapid recovery of the response can occur upon refeeding adequate or high levels of protein.", "contents": "alpha-Aminoisobutyric acid transport in liver slices from rats fed low protein meals. The effect of low protein intake on alpha-aminioisobutyric acid (AIB) transport has been examined in liver slices from meal-fed rats. Treatments (force-feeding casein or gelatin hydrolysates, glycine, or potassium chloride; injecting glucagon, or preincubating liver slices with cyclic AMP) which stimulated transport in control rat fed 3-hour meals containing 18% casein were less effective in rats fed 6% casein meals for 8 days. Responses of protein-depleted rats to glucagon or cyclic AMP had become essentially normal after they had consumed 18% casein meals for 2 days, whereas between 6 to 10 days were required for complete recovery of the response to casein hydrolysate. Stimulation of AIB transport by casein hydrolysate was also normal in depleted rats after they had consumed 40% casein meals for 2 days. Basal, non-stimulated transport of AIB was not significantly depressed in rats fed the low protein diet. Casein hydrolysate-induced increases in hepatic cyclic AMP concentrations were smaller in rats fed low protein meals. The results show that, although various stimuli of hepatic AIB transport become less effective in the protein-deprived rat, relatively rapid recovery of the response can occur upon refeeding adequate or high levels of protein."}
{"id": "PMID:184261", "title": "The redox state and the concentration of ketone bodies in tissues of rats fed carbohydrate free diets.", "content": "The effect of carbohydrate free-low protein diets on the redox potential and ketone body concentrations in liver, muscle, and blood was investigated. Two carbohydrate free diets were fed: 1) A diet in which all the non-protein energy was provided by fatty acids (FA); 2) A similar diet in which the fatty acids were substituted by neutral fat (NF). A carbohydrate rich diet (HC) was fed for comparison. The redox potentials in cytoplasma and mitochondria were calculated from the relative concentrations of the [lactate]:[pyruvate] and [beta-hydroxy-butyrate]:[acetoacetate] couples respectively. In fed rats the cytoplasmic redox potential in liver was much higher in FA than in NF rats, but in fasted NF rats it increased markedly and equaled that of FA rats. In liver mitochondria the redox potential was lower in fed FA than in fed NF rats, while after a 24 hour fast it increased in FA rats and decreased in NF rats. Total ketone body concentrations were high in fed NF rats and increased further in fasted rats, however, in FA rats the high concentrations in the fed state decreased after the short fast. The changes of total ketone-bodies in blood and muscle followed those in liver in both fed and fasted states.", "contents": "The redox state and the concentration of ketone bodies in tissues of rats fed carbohydrate free diets. The effect of carbohydrate free-low protein diets on the redox potential and ketone body concentrations in liver, muscle, and blood was investigated. Two carbohydrate free diets were fed: 1) A diet in which all the non-protein energy was provided by fatty acids (FA); 2) A similar diet in which the fatty acids were substituted by neutral fat (NF). A carbohydrate rich diet (HC) was fed for comparison. The redox potentials in cytoplasma and mitochondria were calculated from the relative concentrations of the [lactate]:[pyruvate] and [beta-hydroxy-butyrate]:[acetoacetate] couples respectively. In fed rats the cytoplasmic redox potential in liver was much higher in FA than in NF rats, but in fasted NF rats it increased markedly and equaled that of FA rats. In liver mitochondria the redox potential was lower in fed FA than in fed NF rats, while after a 24 hour fast it increased in FA rats and decreased in NF rats. Total ketone body concentrations were high in fed NF rats and increased further in fasted rats, however, in FA rats the high concentrations in the fed state decreased after the short fast. The changes of total ketone-bodies in blood and muscle followed those in liver in both fed and fasted states."}
{"id": "PMID:184262", "title": "Gas-liquid chromatographic determination of vitamin D in tuna liver and vitamin D resin oils.", "content": "Gas-liquid chromatographic (GLC) determination of vitamin D3 in tuna liver and vitamin D3 resin oils was investigated and a routine method slightly modified from the previously reported methods (1, 2) was established. Since both tuna liver and vitamin D3 resin oils contained large amounts of sterols, digitonin-Celite column chromatography according to SHEPPARD et al.(4) was used to remove the sterol influence from the unsaponifiable matters of the oils. After collecting the eluate and evaporating the solvent, the residue was subjected to thin-layer chromatography (TLC) using Kieselgel GF254 as an adsorbent and a mixture of n-hexane-ethyl acetate (4: 1) as a developing solvent. The scraped zones corresponding to vitamin D3 and pre-D3 were trimethylsilylated and then applied to the GLC using 1.5% OV-17 packed on Shimalite W (80-100 mesh) as a stationary phase. Trimethylsilylation of the gas chromatograms was an essential procedure, because the peaks of unknown substances in tuna liver oils and lumisterol in vitamin D3 resin oils could not be separated from the peak of pyro-D3 without trimethylsilylation. When the proposed method was applied to the samples, satisfactory results were obtained.", "contents": "Gas-liquid chromatographic determination of vitamin D in tuna liver and vitamin D resin oils. Gas-liquid chromatographic (GLC) determination of vitamin D3 in tuna liver and vitamin D3 resin oils was investigated and a routine method slightly modified from the previously reported methods (1, 2) was established. Since both tuna liver and vitamin D3 resin oils contained large amounts of sterols, digitonin-Celite column chromatography according to SHEPPARD et al.(4) was used to remove the sterol influence from the unsaponifiable matters of the oils. After collecting the eluate and evaporating the solvent, the residue was subjected to thin-layer chromatography (TLC) using Kieselgel GF254 as an adsorbent and a mixture of n-hexane-ethyl acetate (4: 1) as a developing solvent. The scraped zones corresponding to vitamin D3 and pre-D3 were trimethylsilylated and then applied to the GLC using 1.5% OV-17 packed on Shimalite W (80-100 mesh) as a stationary phase. Trimethylsilylation of the gas chromatograms was an essential procedure, because the peaks of unknown substances in tuna liver oils and lumisterol in vitamin D3 resin oils could not be separated from the peak of pyro-D3 without trimethylsilylation. When the proposed method was applied to the samples, satisfactory results were obtained."}
{"id": "PMID:184270", "title": "Inotropic effect of cyclic AMP in calf ventricular muscle studied by a cut end method.", "content": "1. Cyclic AMP was introduced into ventricular muscle by a cut-end method. Trabecular bundles were pulled through a partition which divided the preparation into a loading region and a test region. The loading region was exposed to Ca-free solution, cut transversely near the partition, and then briefly exposed to cyclic AMP. The test region was continually superfused with Tyrode soltuion. 2. In preliminary experiments, cell-to-cell movements were studied in long bundles by including [3H]cyclic AMP in the loading procedure and allowing redistribution to occur. After suitable test periods, the bundles were removed, frozen, and sliced into segments. Segment radioactivity was plotted against distance and fitted by a theoretical diffusion curve. 3. The results showed longitudinal redistribution of label over many cell lengths with an average effective diffusivity of 8 X 10(-7) cm2/sec. This value did not appear sensitive to the length of the test period or to the presence of a phosphodiesterase inhibitor. 4. The metabolic fate of cyclic AMP introduced by the cut-end method was determined by chromatographic separation of [3H]cyclic AMP and its break-down products. Most of the cyclic AMP was metabolized, but the results suggest that cell-to-cell movements of cyclic AMP contribute to the overall redistribution of label. 5. The cut-end method was used to study the influence of cyclic AMP on the contractile activity in the test region. Introduction of cyclic AMP evoked a delayed increase in twitch tension, about 25% above control. The inotropic effect peaked about 50 min after the end of the loading procedure, a delay which seemed compatible with slow longitudinal diffusion into the test region. 6. In control experiments, the cut-end procedure was repeated with 5'AMP (the immediate break-down product of cyclic AMP) instead of cyclic AMP. No delayed increase in twitch tension was observed. 7. Introduction of dibutyryl cyclic AMP increased twitch amplitude by 130%, with a delayed time course similar to that found for cyclic AMP. 8. The results using the cut-end procedure provide new evidence that cyclic AMP helps mediate adrenergic effects on the strength of contraction.", "contents": "Inotropic effect of cyclic AMP in calf ventricular muscle studied by a cut end method. 1. Cyclic AMP was introduced into ventricular muscle by a cut-end method. Trabecular bundles were pulled through a partition which divided the preparation into a loading region and a test region. The loading region was exposed to Ca-free solution, cut transversely near the partition, and then briefly exposed to cyclic AMP. The test region was continually superfused with Tyrode soltuion. 2. In preliminary experiments, cell-to-cell movements were studied in long bundles by including [3H]cyclic AMP in the loading procedure and allowing redistribution to occur. After suitable test periods, the bundles were removed, frozen, and sliced into segments. Segment radioactivity was plotted against distance and fitted by a theoretical diffusion curve. 3. The results showed longitudinal redistribution of label over many cell lengths with an average effective diffusivity of 8 X 10(-7) cm2/sec. This value did not appear sensitive to the length of the test period or to the presence of a phosphodiesterase inhibitor. 4. The metabolic fate of cyclic AMP introduced by the cut-end method was determined by chromatographic separation of [3H]cyclic AMP and its break-down products. Most of the cyclic AMP was metabolized, but the results suggest that cell-to-cell movements of cyclic AMP contribute to the overall redistribution of label. 5. The cut-end method was used to study the influence of cyclic AMP on the contractile activity in the test region. Introduction of cyclic AMP evoked a delayed increase in twitch tension, about 25% above control. The inotropic effect peaked about 50 min after the end of the loading procedure, a delay which seemed compatible with slow longitudinal diffusion into the test region. 6. In control experiments, the cut-end procedure was repeated with 5'AMP (the immediate break-down product of cyclic AMP) instead of cyclic AMP. No delayed increase in twitch tension was observed. 7. Introduction of dibutyryl cyclic AMP increased twitch amplitude by 130%, with a delayed time course similar to that found for cyclic AMP. 8. The results using the cut-end procedure provide new evidence that cyclic AMP helps mediate adrenergic effects on the strength of contraction."}
{"id": "PMID:184271", "title": "Physiological and morphological effects of post-ganglionic axotomy on presynaptic nerve terminals.", "content": "1. Electrophysiological and electron microscope studies were done on cells in the ciliary ganglion of chickens which had been axotomized on the day of hatching. 2. By the third day after post-ganglionic axotomy both electrical and chemical transmission through the ganglion were severely depressed; by the fifth day ganglionic transmission had disappeared. 3. Action potential initiation and conduction in axotomized cells and in their associated presynaptic nerve terminals were unimpaired 3-4 days after axotomy. 4. Depression of ganglionic transmission in 3-4 day axotomized preparations was due to a reduction in amplitude of both the excitatory post-synaptic potential (e.p.s.p.) and the electrical coupling potential in individual ganglion cells. 5. In addition to being reduced in amplitude, e.p.s.p.s in axotomized cells were more subject to fatigue during low frequency (1/sec) stimulation. 6. The reduction in e.p.s.p. amplitude was due to a reduction in both the mean quantal content of the e.p.s.p.s and the calculated depolarization produced by an individual quantum of transmitter. On the average the e.p.s.p. was reduced by a factor of about 4, the mean quantum content to about two thirds normal and the quantal size to about a third normal, compared with responses in unaxotomized cells of the same age. 7. Ultrastructural studies revealed a progressive maturation of pre-synaptic terminals in normal ganglia between 0 and 9 days after hatching. Over this period the content of synaptic vesicles and mitochondria in the terminals increased and the background matrix became more dense. 8. After axotomy these signs of maturation was abolished or reversed, particularly from the third day onward. In addition there was an increase in the number of cell sections in which no synaptic terminals were observed. 9. It was concluded that loss of synaptic transmission was due to at least three factors: a reduction in release of transmitter from presynaptic terminals, a reduction in quantal size, probably due to a loss of post-synaptic sensitivity, and a partial loss of presynaptic contact.", "contents": "Physiological and morphological effects of post-ganglionic axotomy on presynaptic nerve terminals. 1. Electrophysiological and electron microscope studies were done on cells in the ciliary ganglion of chickens which had been axotomized on the day of hatching. 2. By the third day after post-ganglionic axotomy both electrical and chemical transmission through the ganglion were severely depressed; by the fifth day ganglionic transmission had disappeared. 3. Action potential initiation and conduction in axotomized cells and in their associated presynaptic nerve terminals were unimpaired 3-4 days after axotomy. 4. Depression of ganglionic transmission in 3-4 day axotomized preparations was due to a reduction in amplitude of both the excitatory post-synaptic potential (e.p.s.p.) and the electrical coupling potential in individual ganglion cells. 5. In addition to being reduced in amplitude, e.p.s.p.s in axotomized cells were more subject to fatigue during low frequency (1/sec) stimulation. 6. The reduction in e.p.s.p. amplitude was due to a reduction in both the mean quantal content of the e.p.s.p.s and the calculated depolarization produced by an individual quantum of transmitter. On the average the e.p.s.p. was reduced by a factor of about 4, the mean quantum content to about two thirds normal and the quantal size to about a third normal, compared with responses in unaxotomized cells of the same age. 7. Ultrastructural studies revealed a progressive maturation of pre-synaptic terminals in normal ganglia between 0 and 9 days after hatching. Over this period the content of synaptic vesicles and mitochondria in the terminals increased and the background matrix became more dense. 8. After axotomy these signs of maturation was abolished or reversed, particularly from the third day onward. In addition there was an increase in the number of cell sections in which no synaptic terminals were observed. 9. It was concluded that loss of synaptic transmission was due to at least three factors: a reduction in release of transmitter from presynaptic terminals, a reduction in quantal size, probably due to a loss of post-synaptic sensitivity, and a partial loss of presynaptic contact."}
{"id": "PMID:184272", "title": "Reduction in acetylcholine sensitivity of axotomized ciliary ganglion cells.", "content": "1. Isolated cell clusters from ciliary ganglia of 3- to 4-day-old chickens were used to examine the electrical characteristics and sensitivity to iontophoretically applied acetylcholine (ACh) of normal cells and cells that had been axotomized on the day of hatching. 2. Resting potentials, input resistances and capacitances were the same in axotomized cells as in normal cells. These averaged about 70 mV, 165 Momega and 35 pF respectively. 3. Sensitivity to iontophoretically applied ACh was lower in axotomized cells than in normal cells by a factor of about 8. The rise times of the ACh potentials were the same in the two groups; indicating that the reduced sensitivity was not due to a diffusion barrier. 4. The slopes of the dose-reponse curves, plotted on a double-logarithmic scale, suggested that the co-operative action of two ACh molecules was involved in activating a post-synaptic conductance channel. This relation was unaltered by axotomy. 5. The estimated reversal potential for the action of ACh was unchanged after axotomy. 6. Cells in isolated clusters were similar to those in intact ganlia with respect to threshold depolarization, amplitude and time course of action potentials and ability to generate repetitive action potentials. There were no differences in these characteristics between normal and axotomized cells. 7. Cells in the isolated clusters had input resistances which were larger by a factor of 2-3 and capacitances that were smaller by a factor of about 2 than those of cells in intact ganglia. It is suggested that these differences were due to loss of initial segments of axons from the isolated cells. 8. Normal cells in the isolated clusters displayed spontaneous miniature synaptic potentials, indicating that synaptic integrity was maintained during the isolation procedure. As in intact ganglia, no spontaneous activity was observed in axotomized cells.", "contents": "Reduction in acetylcholine sensitivity of axotomized ciliary ganglion cells. 1. Isolated cell clusters from ciliary ganglia of 3- to 4-day-old chickens were used to examine the electrical characteristics and sensitivity to iontophoretically applied acetylcholine (ACh) of normal cells and cells that had been axotomized on the day of hatching. 2. Resting potentials, input resistances and capacitances were the same in axotomized cells as in normal cells. These averaged about 70 mV, 165 Momega and 35 pF respectively. 3. Sensitivity to iontophoretically applied ACh was lower in axotomized cells than in normal cells by a factor of about 8. The rise times of the ACh potentials were the same in the two groups; indicating that the reduced sensitivity was not due to a diffusion barrier. 4. The slopes of the dose-reponse curves, plotted on a double-logarithmic scale, suggested that the co-operative action of two ACh molecules was involved in activating a post-synaptic conductance channel. This relation was unaltered by axotomy. 5. The estimated reversal potential for the action of ACh was unchanged after axotomy. 6. Cells in isolated clusters were similar to those in intact ganlia with respect to threshold depolarization, amplitude and time course of action potentials and ability to generate repetitive action potentials. There were no differences in these characteristics between normal and axotomized cells. 7. Cells in the isolated clusters had input resistances which were larger by a factor of 2-3 and capacitances that were smaller by a factor of about 2 than those of cells in intact ganglia. It is suggested that these differences were due to loss of initial segments of axons from the isolated cells. 8. Normal cells in the isolated clusters displayed spontaneous miniature synaptic potentials, indicating that synaptic integrity was maintained during the isolation procedure. As in intact ganglia, no spontaneous activity was observed in axotomized cells."}
{"id": "PMID:184274", "title": "Current clamp and voltage clamp study of the inhibitory action of DNP on membrane electrical properties of frog auricular heart muscle.", "content": "Current clamp studies showed that after 10 minutes under DNP 10(-4) M the membrane potential does not change significantly while an important shortening of the action potential duration and a diminished amplitude are observed. Voltage clamp studies have been performed on the slow inward and delayed outward currents. DNP 10(-4) M induced a marked decrease of the slow inward current related to the reduction in both conductance and driving force, and a decrease in the amplitude of the delayed current. The decrease of the slow inward current seems to be mainly responsible for the suppression of the plateau of the action potential during metabolic inhibition.", "contents": "Current clamp and voltage clamp study of the inhibitory action of DNP on membrane electrical properties of frog auricular heart muscle. Current clamp studies showed that after 10 minutes under DNP 10(-4) M the membrane potential does not change significantly while an important shortening of the action potential duration and a diminished amplitude are observed. Voltage clamp studies have been performed on the slow inward and delayed outward currents. DNP 10(-4) M induced a marked decrease of the slow inward current related to the reduction in both conductance and driving force, and a decrease in the amplitude of the delayed current. The decrease of the slow inward current seems to be mainly responsible for the suppression of the plateau of the action potential during metabolic inhibition."}
{"id": "PMID:184273", "title": "Effects of botulinum toxin on neuromuscular transmission in the rat.", "content": "1. Botulinum toxin (BoTx) type A partially blocks spontaneous transmitter release from nerve terminals in the rat. Minature end-plate potentials (m.e.p.p.s) are present at all end-plates, initially with a low frequency but increasing with time after posoning. Their amplitude distribution is at first skew with a predominace of very small m.e.p.p.s but, after a few days, larger than normal m.e.p.p.s appear. 2. Tetanic nerve stimulation, Black Widow Spider Venom, the Caionophore A 23187 or mechanical damage to nerve terminals increases the frequency of m.e.p.p.s and alters the amplitude distribution of m.e.p.p.s towards a normal Gaussian one; the m.e.p.p. size approaches that seen at normal end-plates. This was seen at any time after poisoning. 3. Nerve stimulation gives rise to end-plate potentials (e.p.p.s) of low amplitude and high failure rate. Statistical analysis indicates that evoked release is quantal in nature and follows Poisson statistics, quantum size being initially very small, but after a few days approaching normal size. Short-term tetanic nerve stimulation reversibly increases the quantum content of e.p.p.s and during early stages of paralysis long-term (2 hr) stimulation causes an apparently permanent increase in quantum size. 4. Raising the extracellular Ca concentration from 2 to 16 mM increases the frequency of m.e.p.p.s in normal muscle but not in BoTx poisoned ones. K-free medium or ouabain, which are believed to raise the intracellular Ca concentration in nerve terminals, similarly increases m.e.p.p. frequency in normal but not in poisoned muscles. When the Ca-ionophore A 23187 is used together with high extracellular Ca (greater than 4 mM) massive release of transmitter occurs from poisoned terminals. 5. The extracellular Ca concentration which causes  a certain level of transmitter release in reponse to nerve impulses is considerably higher at BoTx poisoned end-plates than at normal ones. The slope value for Ca dependence of transmitter release is about 1-5 compared with about 3 at normal end-plates. 6. Tetraethylammonium (TEA) greatly increases the amount of transmitter released by nerve impulses and restores neuromuscular transmission during all stages of poisoning, although it has not effect on spontaneous transmitter release. In the presence of TEA the power relation between Ca concentration and quantum content at the BoTx poisoned end-plate is similar to that seen at normal end-plates. 7. It is suggested that in BoTx poisoning the mechanism for transmitter release has a reduced sensitivity to Ca, and the level for activation by intracellular Ca is elevated. Once the intracellular concentration of Ca is raised to this level, by tetanic nerve stimulation, mechanical injury to nerve terminals, the Ca-ionophore or the prolongation of the nerve action potential with TEA, augmented transmitter release occurs, similar to that which occurs in normal nerve terminals at a lower level of Ca.", "contents": "Effects of botulinum toxin on neuromuscular transmission in the rat. 1. Botulinum toxin (BoTx) type A partially blocks spontaneous transmitter release from nerve terminals in the rat. Minature end-plate potentials (m.e.p.p.s) are present at all end-plates, initially with a low frequency but increasing with time after posoning. Their amplitude distribution is at first skew with a predominace of very small m.e.p.p.s but, after a few days, larger than normal m.e.p.p.s appear. 2. Tetanic nerve stimulation, Black Widow Spider Venom, the Caionophore A 23187 or mechanical damage to nerve terminals increases the frequency of m.e.p.p.s and alters the amplitude distribution of m.e.p.p.s towards a normal Gaussian one; the m.e.p.p. size approaches that seen at normal end-plates. This was seen at any time after poisoning. 3. Nerve stimulation gives rise to end-plate potentials (e.p.p.s) of low amplitude and high failure rate. Statistical analysis indicates that evoked release is quantal in nature and follows Poisson statistics, quantum size being initially very small, but after a few days approaching normal size. Short-term tetanic nerve stimulation reversibly increases the quantum content of e.p.p.s and during early stages of paralysis long-term (2 hr) stimulation causes an apparently permanent increase in quantum size. 4. Raising the extracellular Ca concentration from 2 to 16 mM increases the frequency of m.e.p.p.s in normal muscle but not in BoTx poisoned ones. K-free medium or ouabain, which are believed to raise the intracellular Ca concentration in nerve terminals, similarly increases m.e.p.p. frequency in normal but not in poisoned muscles. When the Ca-ionophore A 23187 is used together with high extracellular Ca (greater than 4 mM) massive release of transmitter occurs from poisoned terminals. 5. The extracellular Ca concentration which causes  a certain level of transmitter release in reponse to nerve impulses is considerably higher at BoTx poisoned end-plates than at normal ones. The slope value for Ca dependence of transmitter release is about 1-5 compared with about 3 at normal end-plates. 6. Tetraethylammonium (TEA) greatly increases the amount of transmitter released by nerve impulses and restores neuromuscular transmission during all stages of poisoning, although it has not effect on spontaneous transmitter release. In the presence of TEA the power relation between Ca concentration and quantum content at the BoTx poisoned end-plate is similar to that seen at normal end-plates. 7. It is suggested that in BoTx poisoning the mechanism for transmitter release has a reduced sensitivity to Ca, and the level for activation by intracellular Ca is elevated. Once the intracellular concentration of Ca is raised to this level, by tetanic nerve stimulation, mechanical injury to nerve terminals, the Ca-ionophore or the prolongation of the nerve action potential with TEA, augmented transmitter release occurs, similar to that which occurs in normal nerve terminals at a lower level of Ca."}
{"id": "PMID:184275", "title": "Behavior of the contractile vacuole of Tetrahymena pyriformis W: a redescription with comments on the terminology.", "content": "The behavior of the contractile vacuole of Tetrahymena pyriformis W has been recorded and analyzed quantitatively by cinephotography. The vacuole fills in a stepwise fashion by the confluence of ampullae which appear regularly at the beginning of systole and whose membranes are continuous with that of the contractile vacuole throughout the cycle. The vacuole may subsequently fill slowly by a means not discernible by light microscopy. The vacuole rounds up at the beginning of systole and shortly thereafter the ampullae reappear around the perimeter of the vacuole. They are expanded by fluid forced into them from the vacuole. Round-up and the mode of growth of the ampullae indicate that the contractile vacuole is truly contractile. Expulsion occurs soon after the appearance of the ampullae and terminates the cycle. Contraction is initiated at regular intervals by a timing mechanism which is independent of the size of the vacuole. Suitable terminology to describe the structure and behavior of the contractile vacuole is discussed.", "contents": "Behavior of the contractile vacuole of Tetrahymena pyriformis W: a redescription with comments on the terminology. The behavior of the contractile vacuole of Tetrahymena pyriformis W has been recorded and analyzed quantitatively by cinephotography. The vacuole fills in a stepwise fashion by the confluence of ampullae which appear regularly at the beginning of systole and whose membranes are continuous with that of the contractile vacuole throughout the cycle. The vacuole may subsequently fill slowly by a means not discernible by light microscopy. The vacuole rounds up at the beginning of systole and shortly thereafter the ampullae reappear around the perimeter of the vacuole. They are expanded by fluid forced into them from the vacuole. Round-up and the mode of growth of the ampullae indicate that the contractile vacuole is truly contractile. Expulsion occurs soon after the appearance of the ampullae and terminates the cycle. Contraction is initiated at regular intervals by a timing mechanism which is independent of the size of the vacuole. Suitable terminology to describe the structure and behavior of the contractile vacuole is discussed."}
{"id": "PMID:184276", "title": "Changes in rat ovaries of specific binding for LH, FSH and prolactin during the oestrous cycle and pregnancy.", "content": "In cyclic rats, the highest ovarian specific binding for LH was 6-0+/- 2-2% inpro-oestrus. During pregnancy, the specific binding of 125I-labelled bovine LH by rat ovaries increased gradually and reached a maximum of 24-1+/-4-9% between Days 14 and 18 of gestation; a slight decrease in binding was observed at Day 20 of pregnancy. Ovarian specific binding for FSH was also highest in pro-oestrus (8-9+/-2-1%), decreasing to about 50% in oestrus and metoestrus, but staying relatively constant during pregnancy. For prolactin, the specific binding in rat ovaries was highest (7-1+/-1-6%) in pro-oestrus, quite high in metoestrus and dioestrus and low in oestrus. Specific binding increased gradually only after Day 14 of pregnancy. Serum concentrations of rat LH, FSH and prolactin at different stages of the oestrous cycle and during pregnancy were determined by radioimmunoassays, and no obvious correlation was observed between levels of circulating hormones and the specific binding of these hormones in ovarian tissues. Affinity constants (Ka) for the hormones were very similar between ovaries from pro-oestrous rats and late-pregnant rats, being 0-31 X 10(9) M-1 for LH, 0-65 X 10(10)M-1 for FSH, and 1-14 X 10(10)M-1 for prolactin. Increases in specific binding for different hormones were due to increases of total binding sites in the ovary under different physiological states.", "contents": "Changes in rat ovaries of specific binding for LH, FSH and prolactin during the oestrous cycle and pregnancy. In cyclic rats, the highest ovarian specific binding for LH was 6-0+/- 2-2% inpro-oestrus. During pregnancy, the specific binding of 125I-labelled bovine LH by rat ovaries increased gradually and reached a maximum of 24-1+/-4-9% between Days 14 and 18 of gestation; a slight decrease in binding was observed at Day 20 of pregnancy. Ovarian specific binding for FSH was also highest in pro-oestrus (8-9+/-2-1%), decreasing to about 50% in oestrus and metoestrus, but staying relatively constant during pregnancy. For prolactin, the specific binding in rat ovaries was highest (7-1+/-1-6%) in pro-oestrus, quite high in metoestrus and dioestrus and low in oestrus. Specific binding increased gradually only after Day 14 of pregnancy. Serum concentrations of rat LH, FSH and prolactin at different stages of the oestrous cycle and during pregnancy were determined by radioimmunoassays, and no obvious correlation was observed between levels of circulating hormones and the specific binding of these hormones in ovarian tissues. Affinity constants (Ka) for the hormones were very similar between ovaries from pro-oestrous rats and late-pregnant rats, being 0-31 X 10(9) M-1 for LH, 0-65 X 10(10)M-1 for FSH, and 1-14 X 10(10)M-1 for prolactin. Increases in specific binding for different hormones were due to increases of total binding sites in the ovary under different physiological states."}
{"id": "PMID:184279", "title": "The effect of maternal cytomegalovirus infection on preimplantation development in the mouse.", "content": "Mice were inoculated with murine cytomegalovirus at 14 and 7 days before and 1 and 4 days after mating. The effects of maternal infection on early pregnancy were investigated. Inoculation 7 days before and 1 day after mating, i.e. around ovulation and implantation, significantly reduced pregnancy rate. Embryos in these females were developmentally retarded, perhaps because of the inflammatory effect of the infection on the genital tract. Retarded embryos developed normally when cultured.", "contents": "The effect of maternal cytomegalovirus infection on preimplantation development in the mouse. Mice were inoculated with murine cytomegalovirus at 14 and 7 days before and 1 and 4 days after mating. The effects of maternal infection on early pregnancy were investigated. Inoculation 7 days before and 1 day after mating, i.e. around ovulation and implantation, significantly reduced pregnancy rate. Embryos in these females were developmentally retarded, perhaps because of the inflammatory effect of the infection on the genital tract. Retarded embryos developed normally when cultured."}
{"id": "PMID:184281", "title": "Synthesis and antiviral and antimicrobial activity of certain 1-beta-D-ribofuranosyl-4,5-disubstituted imidazoles.", "content": "Starting with AICA ribonucleoside the following nucleosides were prepared. Methyl 5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (5) was converted into methyl 5-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (6) via diazotization in the presence of cuprous chloride. Similarly, 5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuanosyl)imidazole-4-carbonitrile (9) was converted into 5-chloro-, 5-bromo-, and 5-iodo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carbonitrile derivatives. These 5-halogenated imidazole nucleosides were treated with several nucleophiles such as ammonia, hydroxylamine, and hydrogen sulfide to provide, respectively, 5-haloimidazole-4-carboxamide, 5-haloimidazole-4-carboxamidoxime, and 5-haloimidazole-4-thiocarboxamide ribonucleosides. 5-Chloro- or 5-bromo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carbonitrile was treated with potassium hydrosulfide to yield 5-mercapto-1-beta-D-ribofuranosylimidazole-4-thiocarboxamide (16). The catalytic reduction of 5-chloro- or 5-bromo-1-beta-D-ribofuranosylimidazole-4-carboxamidoxime provided 1-beta-D-ribofuranosylimidazole-4-carboxamidines as their hydrochloride and hydrobromide salts, respectively. These nucleosides were tested for in vitro antiviral, antifungal, and antibacterial activity. The 5-halo analogues of 1-beta-D-ribofuranosylimidazole-4-carboxamide showed significant antiviral activity whereas compound 16 was found inhibitory to fungi.", "contents": "Synthesis and antiviral and antimicrobial activity of certain 1-beta-D-ribofuranosyl-4,5-disubstituted imidazoles. Starting with AICA ribonucleoside the following nucleosides were prepared. Methyl 5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (5) was converted into methyl 5-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (6) via diazotization in the presence of cuprous chloride. Similarly, 5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuanosyl)imidazole-4-carbonitrile (9) was converted into 5-chloro-, 5-bromo-, and 5-iodo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carbonitrile derivatives. These 5-halogenated imidazole nucleosides were treated with several nucleophiles such as ammonia, hydroxylamine, and hydrogen sulfide to provide, respectively, 5-haloimidazole-4-carboxamide, 5-haloimidazole-4-carboxamidoxime, and 5-haloimidazole-4-thiocarboxamide ribonucleosides. 5-Chloro- or 5-bromo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carbonitrile was treated with potassium hydrosulfide to yield 5-mercapto-1-beta-D-ribofuranosylimidazole-4-thiocarboxamide (16). The catalytic reduction of 5-chloro- or 5-bromo-1-beta-D-ribofuranosylimidazole-4-carboxamidoxime provided 1-beta-D-ribofuranosylimidazole-4-carboxamidines as their hydrochloride and hydrobromide salts, respectively. These nucleosides were tested for in vitro antiviral, antifungal, and antibacterial activity. The 5-halo analogues of 1-beta-D-ribofuranosylimidazole-4-carboxamide showed significant antiviral activity whereas compound 16 was found inhibitory to fungi."}
{"id": "PMID:184282", "title": "Synthesis and anti-DNA -virus activity of the 5'-monophosphate and the cyclic 3',5'-monophosphate of 9-(beta-D-xylofuranosyl) guanine.", "content": "9-(beta-TD-xylofuranosyl)guanine (xylo-G) was converted chemically to the 9-(beta-D-xylofuranosyl)guanine 5'-monophosphate (xylo-GMP) and 9-(beta-D-xylofuranosyl)guanine cyclic 3',5'-monophosphate (c-xylo-GMP). These compounds were tested against a variety of DNA viruses in tissue culture in parallel with 9-(beta-D-arabinofuranosyl)adenine (ara-A). This evaluation revealed that xylo-G, xylo-GMP, and c-xylo-GMP were all moderately active but less effective than ara-A. When the four compounds were administered intracerebrally as a treatment for herpes virus, type 1 induced encephalitis in mice, c-xylo-GMP exhibited superior activity to that shown by the other three. When administered intraperitoneally, c-xylo-GMP was found to have a therapeutic index of about 4, which is less than that for ara-A (approximately 30) in the same system.", "contents": "Synthesis and anti-DNA -virus activity of the 5'-monophosphate and the cyclic 3',5'-monophosphate of 9-(beta-D-xylofuranosyl) guanine. 9-(beta-TD-xylofuranosyl)guanine (xylo-G) was converted chemically to the 9-(beta-D-xylofuranosyl)guanine 5'-monophosphate (xylo-GMP) and 9-(beta-D-xylofuranosyl)guanine cyclic 3',5'-monophosphate (c-xylo-GMP). These compounds were tested against a variety of DNA viruses in tissue culture in parallel with 9-(beta-D-arabinofuranosyl)adenine (ara-A). This evaluation revealed that xylo-G, xylo-GMP, and c-xylo-GMP were all moderately active but less effective than ara-A. When the four compounds were administered intracerebrally as a treatment for herpes virus, type 1 induced encephalitis in mice, c-xylo-GMP exhibited superior activity to that shown by the other three. When administered intraperitoneally, c-xylo-GMP was found to have a therapeutic index of about 4, which is less than that for ara-A (approximately 30) in the same system."}
{"id": "PMID:184283", "title": "Centrally acting emetics. 10. Rigid dopamine congeners derived from octahydrobenzo[f]quinoline.", "content": "In a study of conformational requirements for certain dopaminergic agonist molecules, a series of conformationally predictable dopamine congeners related to cis- and trans-octahydrobenzo[f]quinoline was prepared. The complexity and equivocal character of the reduction of variously substituted 4-methyl-1,2,3,4,5,6-hexahydrobenzo[f]quinolines were demonstrated and studied. It was shown that several literature methods for reduction of these systems were in error regarding the stereochemical nature of the product(s). It has been concluded that geometrically specific and predictable reductions of these hexahydrobenzo[f]quinolines seem unlikely to attain, and a plausible rationalization for this conclusion has been proposed. Pharmacologic data on the compounds prepared are consistent with our earlier proposals of a biologically significant conformation of dopamine for emesis, the pecking syndrome in pigeons, and other physiological effects.", "contents": "Centrally acting emetics. 10. Rigid dopamine congeners derived from octahydrobenzo[f]quinoline. In a study of conformational requirements for certain dopaminergic agonist molecules, a series of conformationally predictable dopamine congeners related to cis- and trans-octahydrobenzo[f]quinoline was prepared. The complexity and equivocal character of the reduction of variously substituted 4-methyl-1,2,3,4,5,6-hexahydrobenzo[f]quinolines were demonstrated and studied. It was shown that several literature methods for reduction of these systems were in error regarding the stereochemical nature of the product(s). It has been concluded that geometrically specific and predictable reductions of these hexahydrobenzo[f]quinolines seem unlikely to attain, and a plausible rationalization for this conclusion has been proposed. Pharmacologic data on the compounds prepared are consistent with our earlier proposals of a biologically significant conformation of dopamine for emesis, the pecking syndrome in pigeons, and other physiological effects."}
{"id": "PMID:184284", "title": "Synthesis and biological properties of some spin-labeled 9-aminoacridines.", "content": "Five spin-labeled 9-aminoacridines, each bearing either a 4-(2,2,6,6-tetramethyl-1-piperidinyloxy) or a 3-(2,2,5,5-tetramethyl-1-pyrrolidinyloxy) moiety in the 9 position, have been synthesized and assayed for biological activity in three different test systems. Sedimentation velocity measurements indicated that the labels caused unwinding of calf thymus DNA. Those acridines which contained both 6-chloro and 2-methoxy substituents were less toxic to leukemia L1210 in static culture than the corresponding unsubstituted analogues. While the unsubstituted aminoacridines were quite good inhibitors of Escherichia coli DNA-primed RNA polymerase, the 6-chloro-2-methoxy-substituted compounds stimulated this enzyme system. In the presence of E.coliDNA, the ESR spectrum of 4-[(6-chloro-2-methoxy-9-acridinyl)amino]-2,2,6,6-tetramethyl-1-piperidinyloxyl (12) became broad and highly asymmteric with a maximal hyperfine splitting of 57.5 G. This observation suggests that when 12 intercalates into DNA the piperidinyl moiety that bears the nitroxide group becomes highly immobilized. These results suggest that the spin-labeled 9-aminoacridines will be useful probes for nucleic acids.", "contents": "Synthesis and biological properties of some spin-labeled 9-aminoacridines. Five spin-labeled 9-aminoacridines, each bearing either a 4-(2,2,6,6-tetramethyl-1-piperidinyloxy) or a 3-(2,2,5,5-tetramethyl-1-pyrrolidinyloxy) moiety in the 9 position, have been synthesized and assayed for biological activity in three different test systems. Sedimentation velocity measurements indicated that the labels caused unwinding of calf thymus DNA. Those acridines which contained both 6-chloro and 2-methoxy substituents were less toxic to leukemia L1210 in static culture than the corresponding unsubstituted analogues. While the unsubstituted aminoacridines were quite good inhibitors of Escherichia coli DNA-primed RNA polymerase, the 6-chloro-2-methoxy-substituted compounds stimulated this enzyme system. In the presence of E.coliDNA, the ESR spectrum of 4-[(6-chloro-2-methoxy-9-acridinyl)amino]-2,2,6,6-tetramethyl-1-piperidinyloxyl (12) became broad and highly asymmteric with a maximal hyperfine splitting of 57.5 G. This observation suggests that when 12 intercalates into DNA the piperidinyl moiety that bears the nitroxide group becomes highly immobilized. These results suggest that the spin-labeled 9-aminoacridines will be useful probes for nucleic acids."}
{"id": "PMID:184285", "title": "Simultaneous measurements of optical and electrical properties of artificial membranes composed of mitochondrial lipids and their interaction with cytochrome c.", "content": "A newly constructed cell, which allows simultaneous measurements of optical and electrical properties, was used to study bimolecular black membranes composed of beef heart mitochondrial lipids and their interaction with cytochrome c. The results show that these highly charged membranes are stable only in relatively limited ranges of boundary conditions. In 0.1 n KCl their maximum direct current (dc) resistance is 7 X 10(8) Ohm cm2 +/- 10%; the series capacity at 1 kHz is 0.43 muF/cm2 +/- 3%; the entire thickness, determined by optical reflectivity, is 5.8 +/- 0.2 nm. The interaction between oxidized cytochrome c and these lipid membranes is primarily of electrostatic nature, and dependent on the presence of highly charged phospholipids, such as diphosphatidyl glycerol (cardiolipin) and phosphatidyl ethanolamine. The attachment of cytochrome c maximally causes a 2.5-fold increase in reflectivity, without any noticeable change in the capacity. This leads to a subsequent instability of the membrane (i.e., rupture) preceded by a rapid increase of the dc conductivity. This behavior is far less pronounced with reduced cytochrome c.", "contents": "Simultaneous measurements of optical and electrical properties of artificial membranes composed of mitochondrial lipids and their interaction with cytochrome c. A newly constructed cell, which allows simultaneous measurements of optical and electrical properties, was used to study bimolecular black membranes composed of beef heart mitochondrial lipids and their interaction with cytochrome c. The results show that these highly charged membranes are stable only in relatively limited ranges of boundary conditions. In 0.1 n KCl their maximum direct current (dc) resistance is 7 X 10(8) Ohm cm2 +/- 10%; the series capacity at 1 kHz is 0.43 muF/cm2 +/- 3%; the entire thickness, determined by optical reflectivity, is 5.8 +/- 0.2 nm. The interaction between oxidized cytochrome c and these lipid membranes is primarily of electrostatic nature, and dependent on the presence of highly charged phospholipids, such as diphosphatidyl glycerol (cardiolipin) and phosphatidyl ethanolamine. The attachment of cytochrome c maximally causes a 2.5-fold increase in reflectivity, without any noticeable change in the capacity. This leads to a subsequent instability of the membrane (i.e., rupture) preceded by a rapid increase of the dc conductivity. This behavior is far less pronounced with reduced cytochrome c."}
{"id": "PMID:184294", "title": "Localization and histochemical correlation of 73As by whole-body autoradiography in mice.", "content": "Whole-body sagittal sections of mice administered [73As] H3AsO4 intravenously were processed for autoradiography and histochemistry for glucose-6-phosphatase or alkaline phosphatase. The intense localization of 73As in bone, kidney cortex, intestinal mucosa, and hair follicles corresponded exactly with the histochemical activity of glucose-6-phosphatase and alkaline phosphatase in sections containing no arsenic. The activity of glucose-6-phosphatase was inhibited in all of these sites in sections containing arsenic.", "contents": "Localization and histochemical correlation of 73As by whole-body autoradiography in mice. Whole-body sagittal sections of mice administered [73As] H3AsO4 intravenously were processed for autoradiography and histochemistry for glucose-6-phosphatase or alkaline phosphatase. The intense localization of 73As in bone, kidney cortex, intestinal mucosa, and hair follicles corresponded exactly with the histochemical activity of glucose-6-phosphatase and alkaline phosphatase in sections containing no arsenic. The activity of glucose-6-phosphatase was inhibited in all of these sites in sections containing arsenic."}
{"id": "PMID:184295", "title": "Hemifacial spasm: importance of a complete investigation.", "content": "The authors report the experience of the Clinique d'O.R.L. de l'Universit\u00e9 de Bordeaux II in the management of hemifacial spasm. The recent diagnostic and therapeutic progress in otoneurology has revealed an organic etiology for many cases of hemifacial spasm. The recent diagnostic and therapeutic progress in otoneurology has revealed an organic etiology for many cases of hemifacial spasm. From their experience, they propose a complete investigation for all cases of hemifacial spasm. The disorder is labelled as being idiopathic only if the complete investigation is negative.", "contents": "Hemifacial spasm: importance of a complete investigation. The authors report the experience of the Clinique d'O.R.L. de l'Universit\u00e9 de Bordeaux II in the management of hemifacial spasm. The recent diagnostic and therapeutic progress in otoneurology has revealed an organic etiology for many cases of hemifacial spasm. The recent diagnostic and therapeutic progress in otoneurology has revealed an organic etiology for many cases of hemifacial spasm. From their experience, they propose a complete investigation for all cases of hemifacial spasm. The disorder is labelled as being idiopathic only if the complete investigation is negative."}
{"id": "PMID:184296", "title": "Induction of murine p30 by superinfecting herpesviruses.", "content": "The interaction of endogenous type C viruses with superinfecting herpes simplex virus type 2 (HSV-2) was investigated in two murine cell lines. Replication of HSV-2 was suboptimal in random-bred Swiss/3T3A cells and, in initial experiments, infection with a low virus-to-cell ratio resulted in carrier cultures with enhanced murine leukemia virus (MuLV) p30 expression. Immunofluorescence tests with Swiss/3T3A cells productively infected with HSV-2 also showed HSV-associated cytoplasmic antigens and enhanced MuLV p30 expression when compared with uninfected controls. Inactivation of HSV-2 with UV light did not abolish this reaction, although the number of cells expressing p30 was reduced. HSV-2 replicated more efficiently in a line of NIH Swiss cells (N c1 A c1 10). These cells are not readily inducible for type C expression by conventional methods; however, untreated and UV-inactivated HSV-2 induced both HSV-2-associated antigens and MuLV p30 in these cells. Although the Birch strain of human cytomegalovirus induced MuLV p30, neither mouse cytomegalovirus nor vesicular stomatitis virus induced MuLV p30 in either cell line.", "contents": "Induction of murine p30 by superinfecting herpesviruses. The interaction of endogenous type C viruses with superinfecting herpes simplex virus type 2 (HSV-2) was investigated in two murine cell lines. Replication of HSV-2 was suboptimal in random-bred Swiss/3T3A cells and, in initial experiments, infection with a low virus-to-cell ratio resulted in carrier cultures with enhanced murine leukemia virus (MuLV) p30 expression. Immunofluorescence tests with Swiss/3T3A cells productively infected with HSV-2 also showed HSV-associated cytoplasmic antigens and enhanced MuLV p30 expression when compared with uninfected controls. Inactivation of HSV-2 with UV light did not abolish this reaction, although the number of cells expressing p30 was reduced. HSV-2 replicated more efficiently in a line of NIH Swiss cells (N c1 A c1 10). These cells are not readily inducible for type C expression by conventional methods; however, untreated and UV-inactivated HSV-2 induced both HSV-2-associated antigens and MuLV p30 in these cells. Although the Birch strain of human cytomegalovirus induced MuLV p30, neither mouse cytomegalovirus nor vesicular stomatitis virus induced MuLV p30 in either cell line."}
{"id": "PMID:184297", "title": "Antigens and DNA of a chimpanzee agent related to Epstein-Barr virus.", "content": "Biological and biochemical studies of the herpesvirus of chimpanzees previously demonstrated to be antigenically related to human Epstein-Barr virus (EBV) indicated that the agent is similar to EBV in that: (i) leukocyte culture of chimpanzees whose sera contained antibody against EBV capsid antigen could yield long-term lymphoblastoid cell lines (Ch-LCL) with B-cell characteristics; (ii) the DNA of Ch-LCL contained sequences homologous to approximately 35 to 45% of human EBV; (iii) Ch-LCL contained an intranuclear antigen, Ch-NA, that could be identified with some chimpanzee or orangutan serum in anticomplimentary immunofluorescence assays; and (iv) treatment of Ch-LCL with iododeoxyuridine resulted in expression of new antigenic activity that reacted with EA+ but not EA- human sera. Two lines of evidence indicate that the chimpanzee agent, although related to human EBV, is a distinct agent: (i) Ch-NA was antigenically distinct from EBV-rebv infection although it cross-reacts of a limited extent with a minor component of EBNA; and (ii) Ch-LCL are missing 55 to 65% of the DNA sequences of human EBV.", "contents": "Antigens and DNA of a chimpanzee agent related to Epstein-Barr virus. Biological and biochemical studies of the herpesvirus of chimpanzees previously demonstrated to be antigenically related to human Epstein-Barr virus (EBV) indicated that the agent is similar to EBV in that: (i) leukocyte culture of chimpanzees whose sera contained antibody against EBV capsid antigen could yield long-term lymphoblastoid cell lines (Ch-LCL) with B-cell characteristics; (ii) the DNA of Ch-LCL contained sequences homologous to approximately 35 to 45% of human EBV; (iii) Ch-LCL contained an intranuclear antigen, Ch-NA, that could be identified with some chimpanzee or orangutan serum in anticomplimentary immunofluorescence assays; and (iv) treatment of Ch-LCL with iododeoxyuridine resulted in expression of new antigenic activity that reacted with EA+ but not EA- human sera. Two lines of evidence indicate that the chimpanzee agent, although related to human EBV, is a distinct agent: (i) Ch-NA was antigenically distinct from EBV-rebv infection although it cross-reacts of a limited extent with a minor component of EBNA; and (ii) Ch-LCL are missing 55 to 65% of the DNA sequences of human EBV."}
{"id": "PMID:184298", "title": "Structure of a defective simian virus 40 genome bearing an operator from bacteriophage lambda.", "content": "We examined further the physical structure of the simian virus 40 (SV40) and bacteriophage lambda DNA sequences in an SV40-lambda hybrid that had been propagated in monkey kidney cells. The SV40 vector portion of the hybrid, which was a small fragment isolated from a reiteration mutant of SV40, contained the site for initiation of SV40 DNA replication. Electron microscope heteroduplex and restriction endonuclease analyses revealed a tandem duplication of the SV40 vector segment linked to a 2,300-base pair portion (lambda map units 71 to 76) of the lambda immunity region. The defective hybrid genome thus harbors two origins for SV40 DNA replication in addition to the leftward operator and the N gene of lambda.", "contents": "Structure of a defective simian virus 40 genome bearing an operator from bacteriophage lambda. We examined further the physical structure of the simian virus 40 (SV40) and bacteriophage lambda DNA sequences in an SV40-lambda hybrid that had been propagated in monkey kidney cells. The SV40 vector portion of the hybrid, which was a small fragment isolated from a reiteration mutant of SV40, contained the site for initiation of SV40 DNA replication. Electron microscope heteroduplex and restriction endonuclease analyses revealed a tandem duplication of the SV40 vector segment linked to a 2,300-base pair portion (lambda map units 71 to 76) of the lambda immunity region. The defective hybrid genome thus harbors two origins for SV40 DNA replication in addition to the leftward operator and the N gene of lambda."}
{"id": "PMID:184299", "title": "Suppression of glycoprotein formation of Semliki Forest, influenza, and avian sarcoma virus by tunicamycin.", "content": "Tunicamycin, a new antibiotic, halts the formation of physical particles of Semliki forest and fowl plague virus, whereas avian oncornavirus particles which show a reduction in infectivity and do not contain detectable labeled glycoprotein are released in the presence of the drug. In Semliki forest virus-infected cells only the protein moieties of the glycoproteins could be labeled. In cells infected with fowl plague and avian sarcoma virus neither intact glycoproteins nor their protein moieties could be detected. By using a protease inhibitor (N-alpha-p-tosyl-L-lysin chloromethyl ketone, TLCK) it could be shown, however, that the carbohydrate-free hemagglutinin precursor of influenza virus is synthesized but is presumably degraded by intracellular proteases in the absence of TLCK as a consequence of the lack of carbohydrate.", "contents": "Suppression of glycoprotein formation of Semliki Forest, influenza, and avian sarcoma virus by tunicamycin. Tunicamycin, a new antibiotic, halts the formation of physical particles of Semliki forest and fowl plague virus, whereas avian oncornavirus particles which show a reduction in infectivity and do not contain detectable labeled glycoprotein are released in the presence of the drug. In Semliki forest virus-infected cells only the protein moieties of the glycoproteins could be labeled. In cells infected with fowl plague and avian sarcoma virus neither intact glycoproteins nor their protein moieties could be detected. By using a protease inhibitor (N-alpha-p-tosyl-L-lysin chloromethyl ketone, TLCK) it could be shown, however, that the carbohydrate-free hemagglutinin precursor of influenza virus is synthesized but is presumably degraded by intracellular proteases in the absence of TLCK as a consequence of the lack of carbohydrate."}
{"id": "PMID:184300", "title": "Configurational variants of oncornavirus RNAs.", "content": "Heating oncornavirus RNAs at temperatures insufficient for complete denaturation results in forms migrating between the native form (vRNA) and the completely denatured form (vRNA) after gel electrophoresis. Intermediate forms from Rous sarcoma virus or murine leukemia virus were isolated after heating of vRNA's at 58 degrees C and sedimenting in sucrose gradients, and at least four intermediates could be identified in each case. Melting of feline virus (RD-114) RNA produced one major intermediate which required a comparatively high temperature to denature, and a second intermediate occurring in conditions of low ionic strength. Although the subunit model for oncornavirus RNA is not excluded by these data, we propose that vRNA, vRNA', and intermediates may be configurational variants of the same molecule, and a monomer model for oncornavirus RNA is presented.", "contents": "Configurational variants of oncornavirus RNAs. Heating oncornavirus RNAs at temperatures insufficient for complete denaturation results in forms migrating between the native form (vRNA) and the completely denatured form (vRNA) after gel electrophoresis. Intermediate forms from Rous sarcoma virus or murine leukemia virus were isolated after heating of vRNA's at 58 degrees C and sedimenting in sucrose gradients, and at least four intermediates could be identified in each case. Melting of feline virus (RD-114) RNA produced one major intermediate which required a comparatively high temperature to denature, and a second intermediate occurring in conditions of low ionic strength. Although the subunit model for oncornavirus RNA is not excluded by these data, we propose that vRNA, vRNA', and intermediates may be configurational variants of the same molecule, and a monomer model for oncornavirus RNA is presented."}
{"id": "PMID:184301", "title": "Physical and metabolic requirements for early interaction of poliovirus and human rhinovirus with HeLa cells.", "content": "Attachment, \"\"tight binding'' and eclipse of radioactive poliovirus 2 (P2) and human rhinovirus 2 (HRV 2) were investigated. The activation energy for attachment of both HRV2 and P2 was about 13 kcal/mol. HRV2 differed from P2 in two respects: the Arrhenius plot for attachment of HRV2 showed a break at 15 to 19 degrees C when the cells were first treated several hours at 0 degrees C, and attachment of HRV2 was inhibited by treatment of cells with metabolic poisons able to reduce cellular ATP by more than 90%. Tight binding was determined by isolation of a specific P2-membrane complex or by loss of EDTA dissociability of HRV2. Tight binding of both viruses was slowed by 0.01 M iodoacetamide but not by 0.02 M F-; F- plus 0.002 M CN- slowed tight binding of HRV2 but not of P2. Eclipse, the irreversible alteration of parental virions, was detected by isolation of cell-associated subviral particles or by loss of cell-associated infectious virus. Eclipse of both viruses is slowed by iodoacetamide or F-. It seems likely that the early steps of infection with picornaviruses may be sensitive to alterations in the cell membrane produced by metabolic inhibitors or by treatment at low temperature.", "contents": "Physical and metabolic requirements for early interaction of poliovirus and human rhinovirus with HeLa cells. Attachment, \"\"tight binding'' and eclipse of radioactive poliovirus 2 (P2) and human rhinovirus 2 (HRV 2) were investigated. The activation energy for attachment of both HRV2 and P2 was about 13 kcal/mol. HRV2 differed from P2 in two respects: the Arrhenius plot for attachment of HRV2 showed a break at 15 to 19 degrees C when the cells were first treated several hours at 0 degrees C, and attachment of HRV2 was inhibited by treatment of cells with metabolic poisons able to reduce cellular ATP by more than 90%. Tight binding was determined by isolation of a specific P2-membrane complex or by loss of EDTA dissociability of HRV2. Tight binding of both viruses was slowed by 0.01 M iodoacetamide but not by 0.02 M F-; F- plus 0.002 M CN- slowed tight binding of HRV2 but not of P2. Eclipse, the irreversible alteration of parental virions, was detected by isolation of cell-associated subviral particles or by loss of cell-associated infectious virus. Eclipse of both viruses is slowed by iodoacetamide or F-. It seems likely that the early steps of infection with picornaviruses may be sensitive to alterations in the cell membrane produced by metabolic inhibitors or by treatment at low temperature."}
{"id": "PMID:184302", "title": "Glycosylation sites of vesicular stomatitis virus glycoprotein.", "content": "Detailed analysis on DEAE-Sephadex of the tryptic digestion products of the glycoprotein from vesicular stomatitis virus grown in HeLa suspension cultures revealed the presence of two major and several minor sugar-labeled species. The minor tryptic glycopeptides were converted to one of the two major glycopeptide species by treatment with neuraminidase. Thus, vesicular stomatitis virus glycoprotein contains only two oligosaccharide side chains that are heterogeneous in their sialic acid content.", "contents": "Glycosylation sites of vesicular stomatitis virus glycoprotein. Detailed analysis on DEAE-Sephadex of the tryptic digestion products of the glycoprotein from vesicular stomatitis virus grown in HeLa suspension cultures revealed the presence of two major and several minor sugar-labeled species. The minor tryptic glycopeptides were converted to one of the two major glycopeptide species by treatment with neuraminidase. Thus, vesicular stomatitis virus glycoprotein contains only two oligosaccharide side chains that are heterogeneous in their sialic acid content."}
{"id": "PMID:184303", "title": "Natural immunity in mice to structural polypeptides of endogenous type C RNA viruses.", "content": "The immunological responses of inbred mice to structural components of one class of endogenous virus were investigated by means of radioimmunoassays utilizing highly purified viral proteins. Naturally occurring antiviral antibodies were demonstrated only in those strains possessing information for induction of a mouse cell-tropic endogenous virus. Moreover, these antibodies invariably appeared subsequent to the detection of spontaneous replication of this virus in the same animal. The immune responses elicited were much stronger against endogenous viral gp70 than p30, consistent with previous findings of tolerance in the mouse to the major structural antigen of its endogenous virus. However, the demonstration of an immune response to p30 under conditions of both natural and experimental immunization establishes that tolerance to this viral antigen can be overcome.", "contents": "Natural immunity in mice to structural polypeptides of endogenous type C RNA viruses. The immunological responses of inbred mice to structural components of one class of endogenous virus were investigated by means of radioimmunoassays utilizing highly purified viral proteins. Naturally occurring antiviral antibodies were demonstrated only in those strains possessing information for induction of a mouse cell-tropic endogenous virus. Moreover, these antibodies invariably appeared subsequent to the detection of spontaneous replication of this virus in the same animal. The immune responses elicited were much stronger against endogenous viral gp70 than p30, consistent with previous findings of tolerance in the mouse to the major structural antigen of its endogenous virus. However, the demonstration of an immune response to p30 under conditions of both natural and experimental immunization establishes that tolerance to this viral antigen can be overcome."}
{"id": "PMID:184304", "title": "Evidence of ambiguous processing and selective degradation in the noncapsid proteins of rhinovirus 1A.", "content": "Pulse-chase kinetics and extensive pactamycin mapping studies show that the translation of rhinovirus 1A proceeds in the order: initiate-P1-S-P2-terminate, where P1 is the precursor to the capsid proteins, S is a stable primary gene product, and P2 is the precursor to a family of noncapsid products. Initial examination of the molar stoichiometry of the families of rhinoviral proteins in infected cells suggested that both the P1 and P2 regions were translated more frequently than the S region. However, we show that this apparent asymmetry in translation is an artifact arising from two phenomena: (i) ambiguous cleavage sites which result in two alternative products from the S region, having apparent molecular weights of 47,000 and 38,000, and (ii) several fates for the P2 precursors, including degradation of 35 to 45% of the P2 family to small unidentifiable products. Another artifact, a time-dependent shift in the pactamycin mapping position of polypeptide r-39, was traced to a selective inhibition of the rate of cleavage of its precursor (peak 76). The processing rate of the capsid precursor (peak 92) was not retarded by pactamycin.", "contents": "Evidence of ambiguous processing and selective degradation in the noncapsid proteins of rhinovirus 1A. Pulse-chase kinetics and extensive pactamycin mapping studies show that the translation of rhinovirus 1A proceeds in the order: initiate-P1-S-P2-terminate, where P1 is the precursor to the capsid proteins, S is a stable primary gene product, and P2 is the precursor to a family of noncapsid products. Initial examination of the molar stoichiometry of the families of rhinoviral proteins in infected cells suggested that both the P1 and P2 regions were translated more frequently than the S region. However, we show that this apparent asymmetry in translation is an artifact arising from two phenomena: (i) ambiguous cleavage sites which result in two alternative products from the S region, having apparent molecular weights of 47,000 and 38,000, and (ii) several fates for the P2 precursors, including degradation of 35 to 45% of the P2 family to small unidentifiable products. Another artifact, a time-dependent shift in the pactamycin mapping position of polypeptide r-39, was traced to a selective inhibition of the rate of cleavage of its precursor (peak 76). The processing rate of the capsid precursor (peak 92) was not retarded by pactamycin."}
{"id": "PMID:184305", "title": "Cell-free translation of virion RNA from nondefective and transformation-defective Rous sarcoma viruses.", "content": "Nondefective and transformation-defective virion subunit RNAs from two strains of Rous sarcoma virus (RSV) were translated in cell-free systems derived from Krebs IIA ascites cells, wheat germ, and L-cells. In each case the predominant viral-specific product was a polypeptide of molecular weight 76,000 that is related to the internal viral group-specific antigens, as judged by immunoprecipitation with monospecific antisera and tryptic peptide fingerprinting. No difference could be detected between the translation products of 35S RNA from nondefective and transformation-defective RSV virions, nor of 35S RNA from different strains of RSV. The 76,000-molecular-weight polypeptide synthesized in response to 35S RNA in vitro was labeled with formyl-methionine from initiator tRNA. Models for viral protein synthesis are discussed in the light of these results, and arguments positioning the group-specific antigen gene at the 5' end of the 35S RNA are presented.", "contents": "Cell-free translation of virion RNA from nondefective and transformation-defective Rous sarcoma viruses. Nondefective and transformation-defective virion subunit RNAs from two strains of Rous sarcoma virus (RSV) were translated in cell-free systems derived from Krebs IIA ascites cells, wheat germ, and L-cells. In each case the predominant viral-specific product was a polypeptide of molecular weight 76,000 that is related to the internal viral group-specific antigens, as judged by immunoprecipitation with monospecific antisera and tryptic peptide fingerprinting. No difference could be detected between the translation products of 35S RNA from nondefective and transformation-defective RSV virions, nor of 35S RNA from different strains of RSV. The 76,000-molecular-weight polypeptide synthesized in response to 35S RNA in vitro was labeled with formyl-methionine from initiator tRNA. Models for viral protein synthesis are discussed in the light of these results, and arguments positioning the group-specific antigen gene at the 5' end of the 35S RNA are presented."}
{"id": "PMID:184307", "title": "Osteosclerotic myeloma.", "content": "A 49-year-old man with an osteosclerotic lesion of a thoracic vertebra had peripheral neuropathy, lymphadenopathy, and elevated serum alkaline phosphatase and monoclonal immunoglobulin levels in the cerebrospinal fluid. These findings, not usually seen in \"\"classical'' myeloma, have been noted in different combinations in the osteosclerotic variety.", "contents": "Osteosclerotic myeloma. A 49-year-old man with an osteosclerotic lesion of a thoracic vertebra had peripheral neuropathy, lymphadenopathy, and elevated serum alkaline phosphatase and monoclonal immunoglobulin levels in the cerebrospinal fluid. These findings, not usually seen in \"\"classical'' myeloma, have been noted in different combinations in the osteosclerotic variety."}
{"id": "PMID:184308", "title": "The mechanism of low-renin hypertension: aldosterone response to sodium restriction and upright posture, angiotensin II, ACTH and potassium in patients with hypertension.", "content": "Plasma renin activity and aldosterone were measured simultaneously in 67 out-patients with essential hypertension. High aldosterone was more often in patients with high renin, and low levels of aldosterone were usual in those with low and normal renin. In order to study the mechanism by which aldosterone and renin acitvity are suppressed in low-renin hypertension, 25 patients (13 normal-renin hypertensives, 10 low-renin patients including 4 non-responders and two DOC excess hypertensives) were investigated as inpatients. Plasma renin activity, aldosterone and cortisol were determined by the following stimualtions with 3 days of sodium restriction and 2 hours of upright posture, angiotensin II infusion (at a dose which increased 20mmHg of diastolic blood pressure), ACTH administration (rapid i.m. injection of 0.25 mg of alpha 1-24  preparation) and potassium infusion (30 meq of potassium i.v.). Responses of aldosterone in normal-renin hypertensives to all stimulations were 3-5 fold increases from bases line values. Low-renin hypertensives except two of four non-responders showed the responses similar to those in normal-renin patients. The responses of two of the non-responders were similar to those in DOC excess hypertensives who showed reduced responses of aldosterone to some of these stimulations. Thus, it seems that low-renin hypertension is a clinical entity caused by a variety of mechanisms, and the mechanism by which low-renin hypertension is induced is not explained by one factor such as an unknown mineralocorticoid.", "contents": "The mechanism of low-renin hypertension: aldosterone response to sodium restriction and upright posture, angiotensin II, ACTH and potassium in patients with hypertension. Plasma renin activity and aldosterone were measured simultaneously in 67 out-patients with essential hypertension. High aldosterone was more often in patients with high renin, and low levels of aldosterone were usual in those with low and normal renin. In order to study the mechanism by which aldosterone and renin acitvity are suppressed in low-renin hypertension, 25 patients (13 normal-renin hypertensives, 10 low-renin patients including 4 non-responders and two DOC excess hypertensives) were investigated as inpatients. Plasma renin activity, aldosterone and cortisol were determined by the following stimualtions with 3 days of sodium restriction and 2 hours of upright posture, angiotensin II infusion (at a dose which increased 20mmHg of diastolic blood pressure), ACTH administration (rapid i.m. injection of 0.25 mg of alpha 1-24  preparation) and potassium infusion (30 meq of potassium i.v.). Responses of aldosterone in normal-renin hypertensives to all stimulations were 3-5 fold increases from bases line values. Low-renin hypertensives except two of four non-responders showed the responses similar to those in normal-renin patients. The responses of two of the non-responders were similar to those in DOC excess hypertensives who showed reduced responses of aldosterone to some of these stimulations. Thus, it seems that low-renin hypertension is a clinical entity caused by a variety of mechanisms, and the mechanism by which low-renin hypertension is induced is not explained by one factor such as an unknown mineralocorticoid."}
{"id": "PMID:184324", "title": "A scanning electron microscopic study of SV40 infected cells.", "content": "The surface of the SV40-infected African green monkey kidney (AGMK) cells was studied morphologically by scanning electron microscopy. In 24 hr post infection (p.i.), the cell surface was covered with slightly elongated microvilli. The microvilli increased in number. In 96 hr.p.i. most of the cells showed SV40-specific cytopathic effects (CPE). Nuclear swellings and the elongation of microvilli were eminent. Microvilli were observed projecting with high densities especially on the nuclear portions of the cell surfaces. Features suggesting cytoplasmic vacuolization were also observed in some cells. Spherical particles viewed in some of the cells at the late stage of infection were considered SV40 virions. Their origin was also discussed.", "contents": "A scanning electron microscopic study of SV40 infected cells. The surface of the SV40-infected African green monkey kidney (AGMK) cells was studied morphologically by scanning electron microscopy. In 24 hr post infection (p.i.), the cell surface was covered with slightly elongated microvilli. The microvilli increased in number. In 96 hr.p.i. most of the cells showed SV40-specific cytopathic effects (CPE). Nuclear swellings and the elongation of microvilli were eminent. Microvilli were observed projecting with high densities especially on the nuclear portions of the cell surfaces. Features suggesting cytoplasmic vacuolization were also observed in some cells. Spherical particles viewed in some of the cells at the late stage of infection were considered SV40 virions. Their origin was also discussed."}
{"id": "PMID:184325", "title": "Studies on the interaction between coxsackievirus A9 and HeLa cells. I. Plaque-forming ability of coxsackievirus A9 in HeLa cell cultures.", "content": "Most of the coxsackievirus A9 (CA 9 virus) including the prototype strain formed plaques in HeLa cell monolayers under agar overlay, although they showed little or no cytopathogenicity under fluid medium. These viruses were isolated or passaged in primary cynomolgus monkey kidney (MK) cell cultures, and the infectivity of any strain in terms of plaque-forming units was much higher in MK cells than in HeLa cells, even after plaque purification of the virus in HeLa cell cultures. CA 9 virus contained in the original throat swabs as well as some clones obtained by plaque purification in MK cells failed to form plaques in HeLa cells, but virus preparations obtained after several undiluted passages through MK cells included plaque-formers in HeLa cells, suggesting that such plaque (HeLa)-forming viruses may have developed at a certain rate during multiplication of the original non-plaque (HeLa)-forming virus population in MK cells. Out of four lines of HeLa cells examined, two, including a clonal line S3, failed to support plaque formation by CA 9 virus.", "contents": "Studies on the interaction between coxsackievirus A9 and HeLa cells. I. Plaque-forming ability of coxsackievirus A9 in HeLa cell cultures. Most of the coxsackievirus A9 (CA 9 virus) including the prototype strain formed plaques in HeLa cell monolayers under agar overlay, although they showed little or no cytopathogenicity under fluid medium. These viruses were isolated or passaged in primary cynomolgus monkey kidney (MK) cell cultures, and the infectivity of any strain in terms of plaque-forming units was much higher in MK cells than in HeLa cells, even after plaque purification of the virus in HeLa cell cultures. CA 9 virus contained in the original throat swabs as well as some clones obtained by plaque purification in MK cells failed to form plaques in HeLa cells, but virus preparations obtained after several undiluted passages through MK cells included plaque-formers in HeLa cells, suggesting that such plaque (HeLa)-forming viruses may have developed at a certain rate during multiplication of the original non-plaque (HeLa)-forming virus population in MK cells. Out of four lines of HeLa cells examined, two, including a clonal line S3, failed to support plaque formation by CA 9 virus."}
{"id": "PMID:184326", "title": "Studies on the interaction between coxsackievirus A9 and HeLa cells. II. Mode of growth of coxsackievirus A9 in HeLa cell cultures and the effect of sulfated polysaccharide on plaque formation.", "content": "For the purpose of clarifying the mechanism of plaque formation in HeLa cell cultures by coxsackievirus A9, which does not show definite CPE in fluid cultures, we investigated the growth pattern of the virus in HeLa cells, comparing plaque (HeLA)-forming and non-plaque (HeLa)-forming viruses. It was revealed that the yield of both viruses per cell was nearly the same, but non- plaque (HeLa)-forming virus was far less efficient in infecting HeLa cells. Dextran sulfate was effective in releasing more virus from cells, when HeLa cell cultures were infected with plaque (HeLa)-forming virus, but not in cultures infected with non-plaque (HeLa)-forming virus. From these experimental results, the mechanism by which plaques are formed in HeLa cell cultures by coxsackievirus A9 was discussed.", "contents": "Studies on the interaction between coxsackievirus A9 and HeLa cells. II. Mode of growth of coxsackievirus A9 in HeLa cell cultures and the effect of sulfated polysaccharide on plaque formation. For the purpose of clarifying the mechanism of plaque formation in HeLa cell cultures by coxsackievirus A9, which does not show definite CPE in fluid cultures, we investigated the growth pattern of the virus in HeLa cells, comparing plaque (HeLA)-forming and non-plaque (HeLa)-forming viruses. It was revealed that the yield of both viruses per cell was nearly the same, but non- plaque (HeLa)-forming virus was far less efficient in infecting HeLa cells. Dextran sulfate was effective in releasing more virus from cells, when HeLa cell cultures were infected with plaque (HeLa)-forming virus, but not in cultures infected with non-plaque (HeLa)-forming virus. From these experimental results, the mechanism by which plaques are formed in HeLa cell cultures by coxsackievirus A9 was discussed."}
{"id": "PMID:184329", "title": "Mouse hepatitis virus (MHV-2). Plaque assay and propagation in mouse cell line DBT cells.", "content": "Various factor sinfluencing the plaque formation of mouse hepatitis virus (MHV-2) in DBT cell monolayers were studied and a practical method for plaque assay was developed. Infected DBT cells yielded high-titered virus and were a satisfactory source of complement-fixing viral antigen. The predominant cytopathic effect of MHV-2 in DBT cells was cell rounding and detachment, but no syncytial formation was observed. Fluorescent antibody staining revealed specific fluorescence only in the cytoplasm of infected DBT cells. In one-step growth experiment, newly formed virus was first recognized within 4-hr postinfection and showed subsequently a rapid exponential increase. Release of newly formed virus from the cell was rapid, and a continuous release lasted for a certain period of time. The average per-cell yield of active virus was estimated to be about 6-7 X 10(2) plaque-forming units.", "contents": "Mouse hepatitis virus (MHV-2). Plaque assay and propagation in mouse cell line DBT cells. Various factor sinfluencing the plaque formation of mouse hepatitis virus (MHV-2) in DBT cell monolayers were studied and a practical method for plaque assay was developed. Infected DBT cells yielded high-titered virus and were a satisfactory source of complement-fixing viral antigen. The predominant cytopathic effect of MHV-2 in DBT cells was cell rounding and detachment, but no syncytial formation was observed. Fluorescent antibody staining revealed specific fluorescence only in the cytoplasm of infected DBT cells. In one-step growth experiment, newly formed virus was first recognized within 4-hr postinfection and showed subsequently a rapid exponential increase. Release of newly formed virus from the cell was rapid, and a continuous release lasted for a certain period of time. The average per-cell yield of active virus was estimated to be about 6-7 X 10(2) plaque-forming units."}
{"id": "PMID:184330", "title": "Preferential phosphorylation of NP-protein of influenza A2 virus by virion-associated protein kinase.", "content": "Influenza A2 virions were found to contain protein kinase activity which was stimulated, like in other virion-associated kinases, with Mg++ and Nonidet-P 40 but not with cyclic AMP. The kinase phosphorylated only the NP-protein fraction of the influenza virions in the in vitro reaction. In contrast, none of the influenza virion proteins were phosphorylated significantly during the process of virus production in infected chorioallantoic membranes. The in vitro and in vivo phosphorylations of influenza viral proteins were compared with those of Sendai virus (HVJ).", "contents": "Preferential phosphorylation of NP-protein of influenza A2 virus by virion-associated protein kinase. Influenza A2 virions were found to contain protein kinase activity which was stimulated, like in other virion-associated kinases, with Mg++ and Nonidet-P 40 but not with cyclic AMP. The kinase phosphorylated only the NP-protein fraction of the influenza virions in the in vitro reaction. In contrast, none of the influenza virion proteins were phosphorylated significantly during the process of virus production in infected chorioallantoic membranes. The in vitro and in vivo phosphorylations of influenza viral proteins were compared with those of Sendai virus (HVJ)."}
{"id": "PMID:184337", "title": "[Disorder of the regulation of metabolic processes in coronary arteriosclerosis].", "content": "The activity of adenylcyclase was determined in the thrombocytes of 54 male patients with Stage III coronary atherosclerosis. In 34 patients without signs of ischaemic heart disease the activity of adenylcyclase and phosphodiestherase and the amount of cortisol were determined in blood plasma. In 40 rabbits the same enzymes activity was determined in the thrombocytes and lipid tissue, as well as the amount of lipoproteins of low and very low density was determined in blood plasma prior to and following cortisol administration. The results of clinical and experimental studies have demonstrated that cortisol affects the activity of the adenylcyclase system enzymes in the thrombocytes and lipid tissue, as well as the transformation of lipoproteins in blood plasma.", "contents": "[Disorder of the regulation of metabolic processes in coronary arteriosclerosis]. The activity of adenylcyclase was determined in the thrombocytes of 54 male patients with Stage III coronary atherosclerosis. In 34 patients without signs of ischaemic heart disease the activity of adenylcyclase and phosphodiestherase and the amount of cortisol were determined in blood plasma. In 40 rabbits the same enzymes activity was determined in the thrombocytes and lipid tissue, as well as the amount of lipoproteins of low and very low density was determined in blood plasma prior to and following cortisol administration. The results of clinical and experimental studies have demonstrated that cortisol affects the activity of the adenylcyclase system enzymes in the thrombocytes and lipid tissue, as well as the transformation of lipoproteins in blood plasma."}
{"id": "PMID:184338", "title": "[Lipid composition of lipoproteins and excretion of 17-ketosteroids in coronary arteriosclerosis].", "content": "Blood plasma cholesterol and triglycides concentration lipids composition of lipoproteins as contrasted to the amount of 17-KS and their hormonally active fractions excreted were investigated in 87 patients with myocardial infarction in their history and in 49 practically healthy individuals with no clinical manifestations of ischemic heart disease. In patients with coronary atherosclerosis exhibiting normal blood plasma lipids level, the excretion of 17-KS and of their fractions did not differ from that in healthy individuals. Patients with hyperlipoproteinemia of the IIa, IIb and IV types demonstrated a significantly reduced excretion of 17-KS, etiocholanolone, androsterone and dehydroepiandrosterone. No differences in the excretion of androgens depending upon the type of hyperlipoproteinemia were recorded. A significant negative correlation between the blood plasma cholesterol concentration and the amount of ethocholanolone excreted, the level of hypertriglyceridemin and the passage of dehydroepiandrosterone with urine was noted. In patients with hyperlipoproteinemia and a reduced androgens excretion a deranged lipids composition of lipoproteins was disclosed. A decrease in the amount of androgens leads to disruption of the synthesis and metabolism of lipoproteins and exerts a marked influence on the emergence and further development of hyperlipoproteinemia.", "contents": "[Lipid composition of lipoproteins and excretion of 17-ketosteroids in coronary arteriosclerosis]. Blood plasma cholesterol and triglycides concentration lipids composition of lipoproteins as contrasted to the amount of 17-KS and their hormonally active fractions excreted were investigated in 87 patients with myocardial infarction in their history and in 49 practically healthy individuals with no clinical manifestations of ischemic heart disease. In patients with coronary atherosclerosis exhibiting normal blood plasma lipids level, the excretion of 17-KS and of their fractions did not differ from that in healthy individuals. Patients with hyperlipoproteinemia of the IIa, IIb and IV types demonstrated a significantly reduced excretion of 17-KS, etiocholanolone, androsterone and dehydroepiandrosterone. No differences in the excretion of androgens depending upon the type of hyperlipoproteinemia were recorded. A significant negative correlation between the blood plasma cholesterol concentration and the amount of ethocholanolone excreted, the level of hypertriglyceridemin and the passage of dehydroepiandrosterone with urine was noted. In patients with hyperlipoproteinemia and a reduced androgens excretion a deranged lipids composition of lipoproteins was disclosed. A decrease in the amount of androgens leads to disruption of the synthesis and metabolism of lipoproteins and exerts a marked influence on the emergence and further development of hyperlipoproteinemia."}
{"id": "PMID:184339", "title": "[Adenyl cyclase activity in the tissues and excretion of cyclic adenosine monophosphate in experimental arteriosclerosis].", "content": "The activity of adenylcyclase in the tissues and the elimination of 3',5'-AMP with urine were studied in rabbits and rats with experimentally induced atherosclerosis. The relationship between the concentration of steroid hormones and the activity of adenylcyclase in the adrenals was studied after varying periods of atherogenic diets. The activity of adenylcyclase was shown to decrease in the liver and the adrenal glands, as well as the concentration of corticosterone in the adrenals and the urine excretion of 3',5'-AMP, when the animals were kept on the atherogenic diet for long periods of time. No changes in the activity of adenylcyclase were noted in the lipid tissues of the animals with atherosclerosis. The concentration of the steroid hormones in the animals with experimental atherosclerosis was directly dependent on the activity of adenylcyclase in the tissues and the urine excretion of 3',5'-AMP. The administration of Cortisole resulted in a sharp increase of 3',5'-AMP excretion and an activation of adenylcyclase in the liver and lipid tissues of both normal animals, and those kept on an atherogenic diet.", "contents": "[Adenyl cyclase activity in the tissues and excretion of cyclic adenosine monophosphate in experimental arteriosclerosis]. The activity of adenylcyclase in the tissues and the elimination of 3',5'-AMP with urine were studied in rabbits and rats with experimentally induced atherosclerosis. The relationship between the concentration of steroid hormones and the activity of adenylcyclase in the adrenals was studied after varying periods of atherogenic diets. The activity of adenylcyclase was shown to decrease in the liver and the adrenal glands, as well as the concentration of corticosterone in the adrenals and the urine excretion of 3',5'-AMP, when the animals were kept on the atherogenic diet for long periods of time. No changes in the activity of adenylcyclase were noted in the lipid tissues of the animals with atherosclerosis. The concentration of the steroid hormones in the animals with experimental atherosclerosis was directly dependent on the activity of adenylcyclase in the tissues and the urine excretion of 3',5'-AMP. The administration of Cortisole resulted in a sharp increase of 3',5'-AMP excretion and an activation of adenylcyclase in the liver and lipid tissues of both normal animals, and those kept on an atherogenic diet."}
{"id": "PMID:184342", "title": "[Hormonal regulation of lactation (author's transl)].", "content": "Lactation is controlled by hormones from several endocrine glands. An undisturbed function of the anterior pituitary, of the adrenals, and of the ovaries is a prerequisite for a normal morphogenesis of the mammary gland. The epithelial ducts proliferative under the combined influence of estrogens, glucocorticoids and growth hormone, whereas the lobuloalveolar development depends on progesterone and prolactin in addition to the fore-mentioned hormones. During pregnancy pituitary prolactin may be substituted by placental lactogen. Milk synthesis begins in the second half of pregnancy. It is supported by prolactin and cortisol, which directly act on enzyme activities and processes of differentiation of the alveolar cells. The sudden surge in the secretion of milk after parturition is most likely due to the rapid decline of the serum levels of progesterone. The ejection of milk from the lactating mammary gland is controlled by a neuroendocrine reflex mechanism. Suckling is the appropriate stimulus for the release of oxytocin from the posterior pituitary. Oxytocin increases intramammary pressure by inducing contraction of the myoepithelial cells and thus aids in expelling the milk from the mammary glands. Maintenance of normal postpartum lactation depends on frequent and intensive suckling. Suckling does not only stimulate the release of oxytocin, but also provokes secretion of prolactin and ACTH. This increase in prolactin caused by suckling guarantees galactopoesis. Influencing secretion of prolactin has been proven to be a useful tool for regulating lactation. The experimental ergot derivative 2-Brom-alpha-ergocryptine is a potent suppressor of prolactin secretion from the anterior pituitary. In contrast to estrogens, alone or in combination with progestagens or androgens, this drug is not only effective in suppressing the onset of lactation, but also in inhibiting lactation once milk secretion had started. As to stimulating lactation in the human there is no effective drug available up to now.", "contents": "[Hormonal regulation of lactation (author's transl)]. Lactation is controlled by hormones from several endocrine glands. An undisturbed function of the anterior pituitary, of the adrenals, and of the ovaries is a prerequisite for a normal morphogenesis of the mammary gland. The epithelial ducts proliferative under the combined influence of estrogens, glucocorticoids and growth hormone, whereas the lobuloalveolar development depends on progesterone and prolactin in addition to the fore-mentioned hormones. During pregnancy pituitary prolactin may be substituted by placental lactogen. Milk synthesis begins in the second half of pregnancy. It is supported by prolactin and cortisol, which directly act on enzyme activities and processes of differentiation of the alveolar cells. The sudden surge in the secretion of milk after parturition is most likely due to the rapid decline of the serum levels of progesterone. The ejection of milk from the lactating mammary gland is controlled by a neuroendocrine reflex mechanism. Suckling is the appropriate stimulus for the release of oxytocin from the posterior pituitary. Oxytocin increases intramammary pressure by inducing contraction of the myoepithelial cells and thus aids in expelling the milk from the mammary glands. Maintenance of normal postpartum lactation depends on frequent and intensive suckling. Suckling does not only stimulate the release of oxytocin, but also provokes secretion of prolactin and ACTH. This increase in prolactin caused by suckling guarantees galactopoesis. Influencing secretion of prolactin has been proven to be a useful tool for regulating lactation. The experimental ergot derivative 2-Brom-alpha-ergocryptine is a potent suppressor of prolactin secretion from the anterior pituitary. In contrast to estrogens, alone or in combination with progestagens or androgens, this drug is not only effective in suppressing the onset of lactation, but also in inhibiting lactation once milk secretion had started. As to stimulating lactation in the human there is no effective drug available up to now."}
{"id": "PMID:184343", "title": "[Cerebellar vincristine toxicity (author's transl)].", "content": "The diagnosis of Wilms tumor stage IV was established in a girl of 5 1/2 years of age in July 1972. Nephrektomy was followed by radiotherapy of the tumorbed and the lung metastasis. Thereafter the child was treated with Vincristine (VCR) and Actinomycine D (AMD) for two years. The child has been off treatment for the last 14 months and is free of disease. An intention tremor of the right hand was noted 4 weeks after the 32nd application of VCR and 2 weeks after a viral infection of unknown etiology. The writing proved to be hypermetric. There was no loss of proprioception and thus the symptoms were localized into the right cerebellum. Having excluded other causes (hemorrhage, metastasis) as far as possible and considering unilateral cerebellar encephalitis as very unlikely the cerebellar symptoms were thought to be VCR toxicity.", "contents": "[Cerebellar vincristine toxicity (author's transl)]. The diagnosis of Wilms tumor stage IV was established in a girl of 5 1/2 years of age in July 1972. Nephrektomy was followed by radiotherapy of the tumorbed and the lung metastasis. Thereafter the child was treated with Vincristine (VCR) and Actinomycine D (AMD) for two years. The child has been off treatment for the last 14 months and is free of disease. An intention tremor of the right hand was noted 4 weeks after the 32nd application of VCR and 2 weeks after a viral infection of unknown etiology. The writing proved to be hypermetric. There was no loss of proprioception and thus the symptoms were localized into the right cerebellum. Having excluded other causes (hemorrhage, metastasis) as far as possible and considering unilateral cerebellar encephalitis as very unlikely the cerebellar symptoms were thought to be VCR toxicity."}
{"id": "PMID:184344", "title": "[Adriamycin cardiomyopathy in a child with Wilms tumor and liver metastases (author's transl)].", "content": "Nephrectomy with irradiation was performed in a 3;2 year old boy with Wilms tumor stage IV (livermetastases (liver metastases). Six months later a hemihepatectomy was performed on account of the liver metatases which persisted under a combined Actinomycin Vincristin therapy. A monotherapy with Adriamycin was instituted. The patient developed acute congestive heart failure. The patient developed acute congestive heart failure and showed typical EKG changes after a total dose of 700 mg/M2 of Adriamycin. In comparison to adults children reportedly tolerate somewhat higher total doses of Adriamycin. Therefore it is discussed, if in this case a limitation of liver function by hemihepatectomy and by irradiation has favored the appearance of the Adriamycin-induced cardiomyopathy.", "contents": "[Adriamycin cardiomyopathy in a child with Wilms tumor and liver metastases (author's transl)]. Nephrectomy with irradiation was performed in a 3;2 year old boy with Wilms tumor stage IV (livermetastases (liver metastases). Six months later a hemihepatectomy was performed on account of the liver metatases which persisted under a combined Actinomycin Vincristin therapy. A monotherapy with Adriamycin was instituted. The patient developed acute congestive heart failure. The patient developed acute congestive heart failure and showed typical EKG changes after a total dose of 700 mg/M2 of Adriamycin. In comparison to adults children reportedly tolerate somewhat higher total doses of Adriamycin. Therefore it is discussed, if in this case a limitation of liver function by hemihepatectomy and by irradiation has favored the appearance of the Adriamycin-induced cardiomyopathy."}
{"id": "PMID:184345", "title": "[Combination of the syndrome of Sturge-Weber and the syndrome of Klippel-Tr\u00e9naunay (author's transl)].", "content": "Up until now 39 cases of combined Klippel-Tr\u00e9naunay syndrome and Sturge-Weber syndrome have been described. Here follows the report of a girl, now 4 years of age, displaying a full combination of these syndromes. Only a small part of the body surface is not covered with naevi teleangiectatici laterales. The patient has clear hypertrophy of the left cheek and of the left lower extremity, less noticeable on the left upper extremity. For therapeutic reasons the left side of the head and the left lower extremity were thoroughly angiographically examined--this revealed typical abnormalities. The vessel-alteration of the lower extremity are not extremely far developed and arteriovenous fistulas on a large scale are also absent. This allows us to dismiss the F.P. Weber syndrome on the one hand, while it explains the absence of complications of the Klippel-Tr\u00e9naunay syndrome, as described in literature, on the other. The significance of the alterations of lymph nodes in this disease, which we are the first to describe, is at present not fully clear. The cerebral attacks have until now showed only a temporary response to medication.", "contents": "[Combination of the syndrome of Sturge-Weber and the syndrome of Klippel-Tr\u00e9naunay (author's transl)]. Up until now 39 cases of combined Klippel-Tr\u00e9naunay syndrome and Sturge-Weber syndrome have been described. Here follows the report of a girl, now 4 years of age, displaying a full combination of these syndromes. Only a small part of the body surface is not covered with naevi teleangiectatici laterales. The patient has clear hypertrophy of the left cheek and of the left lower extremity, less noticeable on the left upper extremity. For therapeutic reasons the left side of the head and the left lower extremity were thoroughly angiographically examined--this revealed typical abnormalities. The vessel-alteration of the lower extremity are not extremely far developed and arteriovenous fistulas on a large scale are also absent. This allows us to dismiss the F.P. Weber syndrome on the one hand, while it explains the absence of complications of the Klippel-Tr\u00e9naunay syndrome, as described in literature, on the other. The significance of the alterations of lymph nodes in this disease, which we are the first to describe, is at present not fully clear. The cerebral attacks have until now showed only a temporary response to medication."}
{"id": "PMID:184347", "title": "An NZB virus or NZB mice with viral infections?", "content": "Evidence for and against the possibility that the autoimmune disease of NZB mice has a viral aetiology is presented. It is considered that the case for a viral aetiology is unproven, although the possibility exists that virus may be present in incomplete form. Widely varying experimental results can be expected in experiments involving NZB mice until acceptable standards of mouse strain definition are laid down. Thus the comparison of results obtained from studies of NZB mice of diverse origin may invite misleading conclusions.", "contents": "An NZB virus or NZB mice with viral infections? Evidence for and against the possibility that the autoimmune disease of NZB mice has a viral aetiology is presented. It is considered that the case for a viral aetiology is unproven, although the possibility exists that virus may be present in incomplete form. Widely varying experimental results can be expected in experiments involving NZB mice until acceptable standards of mouse strain definition are laid down. Thus the comparison of results obtained from studies of NZB mice of diverse origin may invite misleading conclusions."}
{"id": "PMID:184351", "title": "Black alcoholism. A comment on NIAAA's plan to combat the problem.", "content": "The National Institute on Alcohol Abuse and Alcoholism's Interim Guidelines for the Establishment of Black Alcoholism Projects are criticized for their possible latent function of redirecting treatment energies away from the primary problem of alcoholism.", "contents": "Black alcoholism. A comment on NIAAA's plan to combat the problem. The National Institute on Alcohol Abuse and Alcoholism's Interim Guidelines for the Establishment of Black Alcoholism Projects are criticized for their possible latent function of redirecting treatment energies away from the primary problem of alcoholism."}
{"id": "PMID:184346", "title": "[Enzyme deficiencies in glycolysis and nucleotide metabolism of red blood cells in nonspherocytic hemolytic anemia (author's transl)].", "content": "The detection of enzyme deficiencies in glycolytic and nucleotide metabolism of human red blood cells has enriched the pathophysiological knowledge on the origin of nonspherocytic hemolytic anemias (NSHA). So far for 11 of 13 glycolytic enzymes deficiencies have been described which are connected with alterations of biochemical enzymatic properties. The most frequent enzyme deficiencies are those of GPI and PK. By performance of special electrophoretic techniques genetic studies allow the demonstration of homozygote and double heterozygote defect carriers. Up to now only adenylate kinase and pyrimidine 5' nucleotidase deficiencies have been detected as genetically determined in altered nucleotide metabolism. The metabolic alterations of several enzymopathies have been characterized so well, that the pathophysiological relations between enzyme deficiency and NSHA probably have been found to be a sufficient explanation.", "contents": "[Enzyme deficiencies in glycolysis and nucleotide metabolism of red blood cells in nonspherocytic hemolytic anemia (author's transl)]. The detection of enzyme deficiencies in glycolytic and nucleotide metabolism of human red blood cells has enriched the pathophysiological knowledge on the origin of nonspherocytic hemolytic anemias (NSHA). So far for 11 of 13 glycolytic enzymes deficiencies have been described which are connected with alterations of biochemical enzymatic properties. The most frequent enzyme deficiencies are those of GPI and PK. By performance of special electrophoretic techniques genetic studies allow the demonstration of homozygote and double heterozygote defect carriers. Up to now only adenylate kinase and pyrimidine 5' nucleotidase deficiencies have been detected as genetically determined in altered nucleotide metabolism. The metabolic alterations of several enzymopathies have been characterized so well, that the pathophysiological relations between enzyme deficiency and NSHA probably have been found to be a sufficient explanation."}
{"id": "PMID:184355", "title": "[Malignant case of angiofibroma (author's transl)].", "content": "Various opinions about the etiopathogenesis of angiofibroma are mentioned. The authors, however, have not succeeded in confirming the frequently mentioned theory of hormonal formation of these tumours. It appears that surgical therapy is the only efficient way today of providing a clear view and a rapid radical removal of tumours, thus reducing the usually profuse haemorrhage during surgical treatment. Pre-operative ligation of the external carotid artery has no noticable effect on the reduction of haemorrhage during the operation. X-rays have no effect on the growth of the tumours. There is no great difference between the histological picture of a primary tumour and that of its recurrences. The malignant course of an angiofibroma in an adult is described which recurred several times and led to the involvement of the endocranium with a letal ending. The histological picture remained unchanged all the time. A spreading of the tumour was noticed in areas distant from the primary localisation of the tumour which we consider to be due to implantation and which indicates great potential growth of tumour cells of this angiofibroma.", "contents": "[Malignant case of angiofibroma (author's transl)]. Various opinions about the etiopathogenesis of angiofibroma are mentioned. The authors, however, have not succeeded in confirming the frequently mentioned theory of hormonal formation of these tumours. It appears that surgical therapy is the only efficient way today of providing a clear view and a rapid radical removal of tumours, thus reducing the usually profuse haemorrhage during surgical treatment. Pre-operative ligation of the external carotid artery has no noticable effect on the reduction of haemorrhage during the operation. X-rays have no effect on the growth of the tumours. There is no great difference between the histological picture of a primary tumour and that of its recurrences. The malignant course of an angiofibroma in an adult is described which recurred several times and led to the involvement of the endocranium with a letal ending. The histological picture remained unchanged all the time. A spreading of the tumour was noticed in areas distant from the primary localisation of the tumour which we consider to be due to implantation and which indicates great potential growth of tumour cells of this angiofibroma."}
{"id": "PMID:184356", "title": "[Lymphographic investigation of the face-neck-region (author's transl)].", "content": "Indirect lymphography is shown to be a technically uncomplicated and easy to use method of displaying the lymph nodes and -vessels of the face and neck regions. \"Lipiodol-Ultra-Fluid\" an oily contrast medium which has used in experiments with minipigs can be radiologically and histologically demonstrated in nodes for months. The histological findings in the course of a year are, at the beginning a phase of non-specific reaction followed by a phase of granulomatous reaction between two weeks and six weeks and finally a third phase where in the medium is stored virtually without histological reaction and is only reduced very slowly. Irreversible destruction of lymph-node structure as not infrequently follows the direct method - due to high-pressure application of the fluid was not evident. It may be assumed that disturbance of lymph node function or changes in lymph flow do not follow the application of the indirect method of lymphography.", "contents": "[Lymphographic investigation of the face-neck-region (author's transl)]. Indirect lymphography is shown to be a technically uncomplicated and easy to use method of displaying the lymph nodes and -vessels of the face and neck regions. \"Lipiodol-Ultra-Fluid\" an oily contrast medium which has used in experiments with minipigs can be radiologically and histologically demonstrated in nodes for months. The histological findings in the course of a year are, at the beginning a phase of non-specific reaction followed by a phase of granulomatous reaction between two weeks and six weeks and finally a third phase where in the medium is stored virtually without histological reaction and is only reduced very slowly. Irreversible destruction of lymph-node structure as not infrequently follows the direct method - due to high-pressure application of the fluid was not evident. It may be assumed that disturbance of lymph node function or changes in lymph flow do not follow the application of the indirect method of lymphography."}
{"id": "PMID:184357", "title": "[Simultaneous estimations of flowrate, total protein,- lysozyme- and immunglobulin-A-secretion in parotid glands with mixed tumours (author's transl)].", "content": "In comparison to normal gland secretions 28 patients with mixed tumors of the parotid glands are examined. Thereby fractionated secretions under rest and stimulation are collected and estimations of flowrate, protein-, lysozyme- and immunglobulin A-secretion are done. The following results are remarkable: 1. After pilocarpinstimulation response of the glands 20 to 30 min later than in normal glands. 2. Protein-secretion is diminished in rest and under stimulation. 3. Immunglobulin A and lysozyme secretion show a greater range than normal glands under rest and stimulation.", "contents": "[Simultaneous estimations of flowrate, total protein,- lysozyme- and immunglobulin-A-secretion in parotid glands with mixed tumours (author's transl)]. In comparison to normal gland secretions 28 patients with mixed tumors of the parotid glands are examined. Thereby fractionated secretions under rest and stimulation are collected and estimations of flowrate, protein-, lysozyme- and immunglobulin A-secretion are done. The following results are remarkable: 1. After pilocarpinstimulation response of the glands 20 to 30 min later than in normal glands. 2. Protein-secretion is diminished in rest and under stimulation. 3. Immunglobulin A and lysozyme secretion show a greater range than normal glands under rest and stimulation."}
{"id": "PMID:184358", "title": "[The epidemiology of gastric cancer (author's transl)].", "content": "Gastric cancer is a highly fatal, common form of cancer in many countries and its medical, surgical, radiologic or combined treatment is very problematic. Thus, a search for its cause and prevention may be more promising than a search for its cure. Epidemiologic data from international studies suggest that environmental factors are more influential than genetic ones in the pathogenesis of gastric cancer, although its causes have not yet been identified. It is likely that the disease has a multi-factorial pathogenesis and that an ingested carcinogen may exert its influence at a time of enhanced susceptibility (damaged mucosa, older age, etc.), particulary in individuals with inherent, elevated risk (males, selected hereditary background etc.). In general, dietary studies have been less rewarding than occupational and geographic-pathologic analyses; such investigations may eventually identify the crude sources of carcinogens which then can be isolated by chemical means.", "contents": "[The epidemiology of gastric cancer (author's transl)]. Gastric cancer is a highly fatal, common form of cancer in many countries and its medical, surgical, radiologic or combined treatment is very problematic. Thus, a search for its cause and prevention may be more promising than a search for its cure. Epidemiologic data from international studies suggest that environmental factors are more influential than genetic ones in the pathogenesis of gastric cancer, although its causes have not yet been identified. It is likely that the disease has a multi-factorial pathogenesis and that an ingested carcinogen may exert its influence at a time of enhanced susceptibility (damaged mucosa, older age, etc.), particulary in individuals with inherent, elevated risk (males, selected hereditary background etc.). In general, dietary studies have been less rewarding than occupational and geographic-pathologic analyses; such investigations may eventually identify the crude sources of carcinogens which then can be isolated by chemical means."}
{"id": "PMID:184362", "title": "A study of the heparin-manganese chloride method for determination of plasma alpha-lipoprotein cholesterol concentration.", "content": "To assess the limits of the heparin MnCl2 precipitation method for quantitation of alpha-lipoprotein cholesterol (C-HDL), effects of varying final McCl2 and heparin concentrations were studied, and the precipitation method was compared to preparative ultracentrifugation. In 65 parallel plasma aliquots, C-HDL (X+/-SE) determined by ultracentrifugation (54.3+/-1.8 mg/dl) correlated significantly (r=0.98, P less than 0.001) with the precipitation method (56.0+/-1.9 mg/dl). C-HDL by ultracentrifugal and precipitation methods were also similar in 16 subjects with triglycerides ranging from 150 to 312 mg/dl (41.4+/-2.6, 43.4+/-2.8, r=0.97, P less than .001). A constant amount of cholesterol in the supernatant was measured over a final McCl2 range of 0.046-0.23 M, and cholesterol values in the supernatant at final McCl2 concentrations of 0.046, 0.05, and 0.055 M did not differ from each other, P greater than 0.1. However, cholesterol levels in the supernatant at final MnCl2 concentration of 0.042 M differed from those at concentrations of 0.046, 0.05, and 0.055 M, P less than 0.05 and the amount of supernatant cholesterol increased as the final McCl2 concentration was reduced from 0.042 to 0.02 M. A constant amount of cholesterol in the supernatant was measured over a heparin concentration range of 92-734 USP units/ml. The final MnCl2 and heparin concentrations of 0.046 M and 184 USP units/ml, which are incorporated in widely used procedures, gave C-HDL values for the precipitation method which were in close agreement with the ultracentrifugal method. There is no evidence for a heparin-Mn++ precipitation of HDL and systematic underestimation of HDL by the precipitation method. However, the final MnCl2 concentration is very near the minimum required for accurate measurement of C-HDL. To preclude incomplete precipitation of low and very low density lipoproteins by insufficient manganese concentration, an increase of the manganese concentration should be considered.", "contents": "A study of the heparin-manganese chloride method for determination of plasma alpha-lipoprotein cholesterol concentration. To assess the limits of the heparin MnCl2 precipitation method for quantitation of alpha-lipoprotein cholesterol (C-HDL), effects of varying final McCl2 and heparin concentrations were studied, and the precipitation method was compared to preparative ultracentrifugation. In 65 parallel plasma aliquots, C-HDL (X+/-SE) determined by ultracentrifugation (54.3+/-1.8 mg/dl) correlated significantly (r=0.98, P less than 0.001) with the precipitation method (56.0+/-1.9 mg/dl). C-HDL by ultracentrifugal and precipitation methods were also similar in 16 subjects with triglycerides ranging from 150 to 312 mg/dl (41.4+/-2.6, 43.4+/-2.8, r=0.97, P less than .001). A constant amount of cholesterol in the supernatant was measured over a final McCl2 range of 0.046-0.23 M, and cholesterol values in the supernatant at final McCl2 concentrations of 0.046, 0.05, and 0.055 M did not differ from each other, P greater than 0.1. However, cholesterol levels in the supernatant at final MnCl2 concentration of 0.042 M differed from those at concentrations of 0.046, 0.05, and 0.055 M, P less than 0.05 and the amount of supernatant cholesterol increased as the final McCl2 concentration was reduced from 0.042 to 0.02 M. A constant amount of cholesterol in the supernatant was measured over a heparin concentration range of 92-734 USP units/ml. The final MnCl2 and heparin concentrations of 0.046 M and 184 USP units/ml, which are incorporated in widely used procedures, gave C-HDL values for the precipitation method which were in close agreement with the ultracentrifugal method. There is no evidence for a heparin-Mn++ precipitation of HDL and systematic underestimation of HDL by the precipitation method. However, the final MnCl2 concentration is very near the minimum required for accurate measurement of C-HDL. To preclude incomplete precipitation of low and very low density lipoproteins by insufficient manganese concentration, an increase of the manganese concentration should be considered."}
{"id": "PMID:184363", "title": "Effect of chronic administration of propranolol on lipoprotein composition.", "content": "Chronic effects of propranolol on plasma lipids and lipoprotein composition were examined in ten patients who had previous strokes and normal plasma lipids. Although plasma triglyceride and total cholesterol were not affected by propranolol, a slight decrease of free cholesterol and phospholipids and a significant increase of free fatty acids were observed in the eighth week of propranolol treatment. Reciprocal changes were observed in lipoprotein composition; these were an increase in lipids of very low-density lipoprotein and a decrease in lipids of both low-density and high-density lipoproteins. Postheparin lipolytic activity was significantly suppressed by the administration of propranolol. Inhibition of lipoprotein lipase by propranolol was considered to have played a role in the reciprocal changes of lipoprotein composition.", "contents": "Effect of chronic administration of propranolol on lipoprotein composition. Chronic effects of propranolol on plasma lipids and lipoprotein composition were examined in ten patients who had previous strokes and normal plasma lipids. Although plasma triglyceride and total cholesterol were not affected by propranolol, a slight decrease of free cholesterol and phospholipids and a significant increase of free fatty acids were observed in the eighth week of propranolol treatment. Reciprocal changes were observed in lipoprotein composition; these were an increase in lipids of very low-density lipoprotein and a decrease in lipids of both low-density and high-density lipoproteins. Postheparin lipolytic activity was significantly suppressed by the administration of propranolol. Inhibition of lipoprotein lipase by propranolol was considered to have played a role in the reciprocal changes of lipoprotein composition."}
{"id": "PMID:184364", "title": "Renal cyclic adenosine monophosphate: an accurate index of parathyroid function.", "content": "Measurement of total urine cyclic 3':5'-adenosine monophosphate (cyclic AMP) only incompletely discriminates between normal, hyperparathyroid, and nonparathyroid hypercalcemic patients. Only a fraction of total urine cyclic AMP is contributed by parathyroid hormone (PTH) action on the proximal nephron (renal cyclic AMP); the remainder is derived from plasma by glomerular filtration. We dtermined total urine and plasma cyclic AMP and PTH (by carboxy-terminal specific radioimmunoassay) in control, hyperparathyroid, nonparathyroid hypercalcemic, and surgically hypoparathyroid patients. Renal cyclic AMP was calculated as total urine cyclic AMP minus the filtered component. Of these determinations, only renal cyclic AMP segregated normal from hyperparathyroid, and hyperparathyroid from nonparathyroid hypercalcemic patients with complete accuracy. These data suggest that measurement of renal cyclic AMP provides an accurate index of parathyroid activity and allows clinical discrimination and appropriate treatment of the sub-groups of patients with malignancy and nonparathyroid hypercalcemia from those with hyperparathyroidism.", "contents": "Renal cyclic adenosine monophosphate: an accurate index of parathyroid function. Measurement of total urine cyclic 3':5'-adenosine monophosphate (cyclic AMP) only incompletely discriminates between normal, hyperparathyroid, and nonparathyroid hypercalcemic patients. Only a fraction of total urine cyclic AMP is contributed by parathyroid hormone (PTH) action on the proximal nephron (renal cyclic AMP); the remainder is derived from plasma by glomerular filtration. We dtermined total urine and plasma cyclic AMP and PTH (by carboxy-terminal specific radioimmunoassay) in control, hyperparathyroid, nonparathyroid hypercalcemic, and surgically hypoparathyroid patients. Renal cyclic AMP was calculated as total urine cyclic AMP minus the filtered component. Of these determinations, only renal cyclic AMP segregated normal from hyperparathyroid, and hyperparathyroid from nonparathyroid hypercalcemic patients with complete accuracy. These data suggest that measurement of renal cyclic AMP provides an accurate index of parathyroid activity and allows clinical discrimination and appropriate treatment of the sub-groups of patients with malignancy and nonparathyroid hypercalcemia from those with hyperparathyroidism."}
{"id": "PMID:184365", "title": "Calcium-dependent regulation of guanosine 3',5'-monophosphate in renal cortex: effects of ionophore A23187 and tetracaine and evidence for independent control of adenosine 3',5'-monophosphate.", "content": "The effects of carbamylcholine (Cch), the divalent cation ionophore A23187 and Ca2+ on the cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic 3',5'-adenosine monophosphate (cAMP) content of rat renal cortical slices were examined. In both the presence and absence of 10 mM theophylline, Cch detectably increased cGMP within 15 sec, with peak responses noted by 2 min. The maximal cGMP response to Cch alone (0.05 mM) was an increase of two- to three-fold over control. Theophylline, which was routinely present in the incubations and which alone increased cGMP of the slices two-fold over basal during 20 min incubations, potentiated the response to Cch (maximal increase, five- to sixfold over theophylline alone). The action of Cch to increase renal cortical cGMP was blocked by prior addition of atropine and was dependent upon the presence of Ca2+ in the incubation media. Exclusion of Ca2+ lowered basal cGMP and abolished increases mediated by Cch, while exclusion of Mg2+ was without detectable effect on cGMP. In slices incubated initially without Ca2+, reexposure to Ca2+ for 1min partially restored the cGMP response to Cch, and reexposure for 3 min completely restored this response. Since prior incubation of tissue in Ca2+-free buffer for only 2 min was sufficient to block the cGMP responses to Cch, depletion of tissue Ca2+ did not appear to be involved. A23187 also increased renal cortical cGMP fivefold in the presence of Ca2+. Its effects were not additive with those of Cch and were not additive with those of Cch and were not expressed by Mg2+ in Ca2+-free media. By contrast, tetracaine, which blocks Ca2+ transport across or binding to biologic membranes, reduced basal cGMP and inhibited the actions of Cch and A23187 to increase cGMP in cortical slices incubated with Ca2+. The action of 1 mM tetracaine to block Cch-mediated increases in cGMP was partially reversed by increasing media Ca2+ from 1.5 to 5 mM, but not by increasing media Mg2+ to 5 mM. In contrast to their effects on cGMP, Cch, A23187, Ca2+ exclusion, and tetracaine did not detectably alter basal renal cortical cAMP or cAMP responses to parathyroid hormone (PTH). Conversely, concentrations of PTH, glucagon, and isoproterenol which maximally increased renal cortical cAMP did not alter cGMP. Furthermore, prior incubation of slices with Cch did not alter their subsequent cAMP response to PTH at a time when cGMP levels were still elevated, while prior incubation with PTH did not affect the subsequent cGMP response to Cch at a time when cAMP was increased. These studies demonstrate modulation of renal cortical cGMP by cholinergic stimuli and Ca2+. They also indicate that cGMP and cAMP in renal cortex can be regulated independently.", "contents": "Calcium-dependent regulation of guanosine 3',5'-monophosphate in renal cortex: effects of ionophore A23187 and tetracaine and evidence for independent control of adenosine 3',5'-monophosphate. The effects of carbamylcholine (Cch), the divalent cation ionophore A23187 and Ca2+ on the cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic 3',5'-adenosine monophosphate (cAMP) content of rat renal cortical slices were examined. In both the presence and absence of 10 mM theophylline, Cch detectably increased cGMP within 15 sec, with peak responses noted by 2 min. The maximal cGMP response to Cch alone (0.05 mM) was an increase of two- to three-fold over control. Theophylline, which was routinely present in the incubations and which alone increased cGMP of the slices two-fold over basal during 20 min incubations, potentiated the response to Cch (maximal increase, five- to sixfold over theophylline alone). The action of Cch to increase renal cortical cGMP was blocked by prior addition of atropine and was dependent upon the presence of Ca2+ in the incubation media. Exclusion of Ca2+ lowered basal cGMP and abolished increases mediated by Cch, while exclusion of Mg2+ was without detectable effect on cGMP. In slices incubated initially without Ca2+, reexposure to Ca2+ for 1min partially restored the cGMP response to Cch, and reexposure for 3 min completely restored this response. Since prior incubation of tissue in Ca2+-free buffer for only 2 min was sufficient to block the cGMP responses to Cch, depletion of tissue Ca2+ did not appear to be involved. A23187 also increased renal cortical cGMP fivefold in the presence of Ca2+. Its effects were not additive with those of Cch and were not additive with those of Cch and were not expressed by Mg2+ in Ca2+-free media. By contrast, tetracaine, which blocks Ca2+ transport across or binding to biologic membranes, reduced basal cGMP and inhibited the actions of Cch and A23187 to increase cGMP in cortical slices incubated with Ca2+. The action of 1 mM tetracaine to block Cch-mediated increases in cGMP was partially reversed by increasing media Ca2+ from 1.5 to 5 mM, but not by increasing media Mg2+ to 5 mM. In contrast to their effects on cGMP, Cch, A23187, Ca2+ exclusion, and tetracaine did not detectably alter basal renal cortical cAMP or cAMP responses to parathyroid hormone (PTH). Conversely, concentrations of PTH, glucagon, and isoproterenol which maximally increased renal cortical cAMP did not alter cGMP. Furthermore, prior incubation of slices with Cch did not alter their subsequent cAMP response to PTH at a time when cGMP levels were still elevated, while prior incubation with PTH did not affect the subsequent cGMP response to Cch at a time when cAMP was increased. These studies demonstrate modulation of renal cortical cGMP by cholinergic stimuli and Ca2+. They also indicate that cGMP and cAMP in renal cortex can be regulated independently."}
{"id": "PMID:184366", "title": "Mechanism of inhibition of organic acid transport in rabbit renal cortex by cyclic AMP.", "content": "The mechanism by which isoproterenol and cyclic AMP inhibit organic acid transport was examined. Accumulation of 131I-Hippuran (S/M) was used as an index of organic acid transport. Propranolol, an antagonist of isoproterenol's beta-adrenergic response, not only inhibited accumulation of Hippuran but, when combined with isoproterenol, caused further inhibition. PTH elicited larger increases than isoproterenol in cortical-slice cyclic AMP content but did not inhibit accumulation of Hippuran. This lack of correlation between a positive effect on the adenylate-cyclase-cyclic AMP system and inhibition of transport was also seen when other agents were tested. Cyclic GMP, which has been postulated to work in opposition to cyclic AMP, was as potent as cyclic AMP in decreasing S/M. The decreasing of S/M by adenine and uric acid could not be related to any known effect of these agents on tissue cyclic AMP content. Similarly, although 0.1 mM theophylline significantly decreased S/M, cortical cyclic-AMP content was not increased until a 100-fold greater concentration of theophylline was employed. The data suggest that the inhibitory effect of these agents was attributable to their molecular configurations, which interact directly with the organic acid transport system rather than indirectly via the adenylate-cyclase-cyclic AMP system.", "contents": "Mechanism of inhibition of organic acid transport in rabbit renal cortex by cyclic AMP. The mechanism by which isoproterenol and cyclic AMP inhibit organic acid transport was examined. Accumulation of 131I-Hippuran (S/M) was used as an index of organic acid transport. Propranolol, an antagonist of isoproterenol's beta-adrenergic response, not only inhibited accumulation of Hippuran but, when combined with isoproterenol, caused further inhibition. PTH elicited larger increases than isoproterenol in cortical-slice cyclic AMP content but did not inhibit accumulation of Hippuran. This lack of correlation between a positive effect on the adenylate-cyclase-cyclic AMP system and inhibition of transport was also seen when other agents were tested. Cyclic GMP, which has been postulated to work in opposition to cyclic AMP, was as potent as cyclic AMP in decreasing S/M. The decreasing of S/M by adenine and uric acid could not be related to any known effect of these agents on tissue cyclic AMP content. Similarly, although 0.1 mM theophylline significantly decreased S/M, cortical cyclic-AMP content was not increased until a 100-fold greater concentration of theophylline was employed. The data suggest that the inhibitory effect of these agents was attributable to their molecular configurations, which interact directly with the organic acid transport system rather than indirectly via the adenylate-cyclase-cyclic AMP system."}
{"id": "PMID:184367", "title": "High density lipoproteinuria in nephrotic syndrome.", "content": "Intravenous administration of the aminonucleoside of puromycin produces the nephrotic syndrome (proteinuria, hypercholesterolemia, hypoproteinemia and edema) in rats. This model is very similar to human nephrotic syndrome caused by various disease states. The current study was designed to assess the nature of urinary lipoproteins in the urine of nephrotic rats, including studies related to the urinary loss of the \"activator\" apolipoproteins for the lipoprotein lipase-triglyceride interaction. Sprague-Dawley rats were given a single intravenous injection (10 mg/100 g) of puromycin aminonucleoside. Plasma and urine were collected before and 7, 18, 29, 36, and 53 days after injection of puromycin. Urine was fractionated in the preparative ultracentrifuge into density (d) fractions less than 1.006 (very low-density lipoproteins), d = 1.006-1.063 (low-density lipoproteins), and d = 1.063-1.210 (high-density lipoproteins--HDL). The cholesterol, triglyceride, phospholipid, and protein content of these fractions was analyzed. Lipoprotein electrophoresis was performed in agarose agar. Urine from normal and nephrotic rats was added to an in vitro system containing lipoprotein lipase and triglyceride. The free fatty acids (FFA) liberated were then measured as an index of urinary activator property on this system. Measurable urinary lipoproteins were present only on days 7 and 18 after induction of the nephrotic syndrome. Coelectrophoresis of these urinary lipoproteins with rat plasma revealed a single band having alpha- (HDL) electrophoretic mobility. The total mean protein content of day-7 urinary lipoproteins (64.3%) was greater than the content of plasma HDL (52.9%). The protein content of urinary lipoproteins also increased with time. When day-7 and day-18 postinjection urine at nephrotic rats was added to the lipoprotein lipase system, the hydrolysis of triglyceride yielded a mean of 0.320 and 0.235 muEq FFA/ml/20 min, respectively. Control rat urine yielded 0.030 muEq FFA/ml/20 min and 0.000 muEq FFA/ml/20 min 7 and 18 days after injection of normal saline, respectively. It is inferred that in this experimental model (1) high-density lipoproteins are probably excreted in the glomerular filtrate, (2) alterations in the composition of the excreted lipoproteins may occur during their passage through the nephron. The possibility that only a selective portion of the HDL spectrum is excreted into the glomerular filtrate cannot be excluded. It is suggested that the urinary or renal loss of this functionally important lipoprotein may contribute to the pathophysiology of hyperlipoproteinemia in the nephrotic syndrome.", "contents": "High density lipoproteinuria in nephrotic syndrome. Intravenous administration of the aminonucleoside of puromycin produces the nephrotic syndrome (proteinuria, hypercholesterolemia, hypoproteinemia and edema) in rats. This model is very similar to human nephrotic syndrome caused by various disease states. The current study was designed to assess the nature of urinary lipoproteins in the urine of nephrotic rats, including studies related to the urinary loss of the \"activator\" apolipoproteins for the lipoprotein lipase-triglyceride interaction. Sprague-Dawley rats were given a single intravenous injection (10 mg/100 g) of puromycin aminonucleoside. Plasma and urine were collected before and 7, 18, 29, 36, and 53 days after injection of puromycin. Urine was fractionated in the preparative ultracentrifuge into density (d) fractions less than 1.006 (very low-density lipoproteins), d = 1.006-1.063 (low-density lipoproteins), and d = 1.063-1.210 (high-density lipoproteins--HDL). The cholesterol, triglyceride, phospholipid, and protein content of these fractions was analyzed. Lipoprotein electrophoresis was performed in agarose agar. Urine from normal and nephrotic rats was added to an in vitro system containing lipoprotein lipase and triglyceride. The free fatty acids (FFA) liberated were then measured as an index of urinary activator property on this system. Measurable urinary lipoproteins were present only on days 7 and 18 after induction of the nephrotic syndrome. Coelectrophoresis of these urinary lipoproteins with rat plasma revealed a single band having alpha- (HDL) electrophoretic mobility. The total mean protein content of day-7 urinary lipoproteins (64.3%) was greater than the content of plasma HDL (52.9%). The protein content of urinary lipoproteins also increased with time. When day-7 and day-18 postinjection urine at nephrotic rats was added to the lipoprotein lipase system, the hydrolysis of triglyceride yielded a mean of 0.320 and 0.235 muEq FFA/ml/20 min, respectively. Control rat urine yielded 0.030 muEq FFA/ml/20 min and 0.000 muEq FFA/ml/20 min 7 and 18 days after injection of normal saline, respectively. It is inferred that in this experimental model (1) high-density lipoproteins are probably excreted in the glomerular filtrate, (2) alterations in the composition of the excreted lipoproteins may occur during their passage through the nephron. The possibility that only a selective portion of the HDL spectrum is excreted into the glomerular filtrate cannot be excluded. It is suggested that the urinary or renal loss of this functionally important lipoprotein may contribute to the pathophysiology of hyperlipoproteinemia in the nephrotic syndrome."}
{"id": "PMID:184371", "title": "Diagnostic value of serum lipoprotein X in jaundice.", "content": "The presence of lipoprotein X (LPX) was assessed in the serum of 61 jaundiced patients and of 41 patients without liver disease. The results are compatible with the reports of other authors that the presence of LPX is a more sensitive indicator of cholestasis than the serum alkaline phosphatase (SAP) level. However, the latter was more useful in excluding the presence of extrahepatic obstruction.", "contents": "Diagnostic value of serum lipoprotein X in jaundice. The presence of lipoprotein X (LPX) was assessed in the serum of 61 jaundiced patients and of 41 patients without liver disease. The results are compatible with the reports of other authors that the presence of LPX is a more sensitive indicator of cholestasis than the serum alkaline phosphatase (SAP) level. However, the latter was more useful in excluding the presence of extrahepatic obstruction."}
{"id": "PMID:184372", "title": "[Experiences with drug therapy of advanced metastatic carcinoma of the breast (author's transl)].", "content": "A group of patients with metastatic breast cancer treated by a distinct drug regimen is analyzed with special respect to clinical and psychological problems. The range of remissions in this study was similar to literature dates. General limitations of indication for cytostatic drugs and of long-time-therapy are discussed. The possible relations of histologic type of primary carcinoma to the efficiency of chemotherapy is mentioned.", "contents": "[Experiences with drug therapy of advanced metastatic carcinoma of the breast (author's transl)]. A group of patients with metastatic breast cancer treated by a distinct drug regimen is analyzed with special respect to clinical and psychological problems. The range of remissions in this study was similar to literature dates. General limitations of indication for cytostatic drugs and of long-time-therapy are discussed. The possible relations of histologic type of primary carcinoma to the efficiency of chemotherapy is mentioned."}
{"id": "PMID:184370", "title": "Lipoproteins versus structural glycoproteins: atherosclerosis as an analogue and competitor of normal connective tissue interactions.", "content": "There is a striking resemblance, in amino-acid composition and properties, between one class of structural glycoproteins from connective tissue and the apo low density lipoproteins (LDL) of blood plasma. It is suggested that there is a structurally specific analogy between the early atherogenic accumulation of LDL (and more particularly Lp(a), in arterial connective tissue and the normal interactions of structural glycoproteins with other connective tissue components, particularly proteoglycans and collagen.", "contents": "Lipoproteins versus structural glycoproteins: atherosclerosis as an analogue and competitor of normal connective tissue interactions. There is a striking resemblance, in amino-acid composition and properties, between one class of structural glycoproteins from connective tissue and the apo low density lipoproteins (LDL) of blood plasma. It is suggested that there is a structurally specific analogy between the early atherogenic accumulation of LDL (and more particularly Lp(a), in arterial connective tissue and the normal interactions of structural glycoproteins with other connective tissue components, particularly proteoglycans and collagen."}
{"id": "PMID:184374", "title": "Methionine-repressible homoserine dehydrogenase of Serratia marcescens: purification and properties.", "content": "Serratia marcescens Sa-3 possesses two homoserine dehydrogenases and neither has any aspartokinase activity unlike the case of Escherichia coli enzymes. The two enzymes have been separated. One of them is active with either NAD+ or NADP+ and has been purified about 180-fold to homogeneity. This enzyme is completely repressed by the presence of 1 mM methionine or homoserine in the growth medium, but its activity is unaffected by any amino acid of the aspartate family either singly or together. In many of its properties (such as pH optimum, Km for substrate and cofactors), it resembles its counterpart in E. coli K12. Potassium ions stabilize the enzyme but are not essential for activity. Its molecular weight is around 155,000 as determined by gel filtration and approximately 76,000 by SDS-polyacrylamide gel electrophoresis. This suggests that the enzyme has two subunits (polypeptide chains) in the molecule: 8 M urea has no effect on enzyme activity. This enzyme represents approximately 30% of the total homoserine dehydrogenase activity of S. marcescens unlike in Salmonella typhimurium and E. coli K12 where it is a minor or a negligible component.", "contents": "Methionine-repressible homoserine dehydrogenase of Serratia marcescens: purification and properties. Serratia marcescens Sa-3 possesses two homoserine dehydrogenases and neither has any aspartokinase activity unlike the case of Escherichia coli enzymes. The two enzymes have been separated. One of them is active with either NAD+ or NADP+ and has been purified about 180-fold to homogeneity. This enzyme is completely repressed by the presence of 1 mM methionine or homoserine in the growth medium, but its activity is unaffected by any amino acid of the aspartate family either singly or together. In many of its properties (such as pH optimum, Km for substrate and cofactors), it resembles its counterpart in E. coli K12. Potassium ions stabilize the enzyme but are not essential for activity. Its molecular weight is around 155,000 as determined by gel filtration and approximately 76,000 by SDS-polyacrylamide gel electrophoresis. This suggests that the enzyme has two subunits (polypeptide chains) in the molecule: 8 M urea has no effect on enzyme activity. This enzyme represents approximately 30% of the total homoserine dehydrogenase activity of S. marcescens unlike in Salmonella typhimurium and E. coli K12 where it is a minor or a negligible component."}
{"id": "PMID:184375", "title": "The effect of p-hydroxymercuribenzoate and congeners on microsomal glucose-6-phosphatase.", "content": "Iodoacetamide, N-ethylmaleimide, p-hydroxymercuribenzoate (p-MB) and HgCl2 were tested as inhibitors of microsomal glucose-6-phosphatase. Iodoacetamide had no effect at 2 mM. N-ethylmaleimide inhibited only crude, but not purified microsomal preparations (M2) or crude microsomes exposed to deoxycholate. 14C-labelled N-ethylmaleimide was not bound by the M2 protein fraction. p-MB inhibited all types of preparations and the inhibition was not counteracted by detergent. A more detailed study was carried out with the purified M2 fraction (specific activity: 2-4 mumoles Pi/min/mg protein). Glucose-6-phosphate hydrolysis was inhibited 50% by 5 X 10(-5) M p-MB. The inhibition was completely reversible by dithiothreitol except when the enzyme was pre-incubated with p-MB in the absence of substrate. Then p-MB accelerated the temperature-dependent inactivation of glucose-6-phosphatase. Binding studies showed that around 3 mumoles 14C-p-MB were incorporated into 100 mg M2 protein regardless of the concentration of mercurial in the incubation mixture. That is, over a 25 fold range of p-MB concentration, causing up to 80% inhibition of enzyme activity, no difference was seen in the amount of labelled p-MB which was irreversibly bound to M2 protein. Kinetically p-MB behaved like a reversible inhibitor and this was confirmed by dilution experiments. Several compounds, including some amino acids, antagonized the inhibition by p-MB. The order of effectiveness was EDTA greater than barbital greater than tryptophan greater than histidine greater than lysine greater than other amino acids. Glycine, Tris and urea were ineffective competitors of p-MB inhibition. Double reciprocal plots showed that the Km for glucose-6-phosphate was increased and the Vmax reduced in the presence of p-MB. HgCl2 was a more effective inhibitor than p-MB with a Ki of 6 X 10(-6) M. We conclude that a reaction of p-MB with M2 sulfhydryls does not play a part in the inhibition of enzyme activity. It is suggested that p-MB may interact with one or more amino acid side chains in such a way that enzyme conformation is altered.", "contents": "The effect of p-hydroxymercuribenzoate and congeners on microsomal glucose-6-phosphatase. Iodoacetamide, N-ethylmaleimide, p-hydroxymercuribenzoate (p-MB) and HgCl2 were tested as inhibitors of microsomal glucose-6-phosphatase. Iodoacetamide had no effect at 2 mM. N-ethylmaleimide inhibited only crude, but not purified microsomal preparations (M2) or crude microsomes exposed to deoxycholate. 14C-labelled N-ethylmaleimide was not bound by the M2 protein fraction. p-MB inhibited all types of preparations and the inhibition was not counteracted by detergent. A more detailed study was carried out with the purified M2 fraction (specific activity: 2-4 mumoles Pi/min/mg protein). Glucose-6-phosphate hydrolysis was inhibited 50% by 5 X 10(-5) M p-MB. The inhibition was completely reversible by dithiothreitol except when the enzyme was pre-incubated with p-MB in the absence of substrate. Then p-MB accelerated the temperature-dependent inactivation of glucose-6-phosphatase. Binding studies showed that around 3 mumoles 14C-p-MB were incorporated into 100 mg M2 protein regardless of the concentration of mercurial in the incubation mixture. That is, over a 25 fold range of p-MB concentration, causing up to 80% inhibition of enzyme activity, no difference was seen in the amount of labelled p-MB which was irreversibly bound to M2 protein. Kinetically p-MB behaved like a reversible inhibitor and this was confirmed by dilution experiments. Several compounds, including some amino acids, antagonized the inhibition by p-MB. The order of effectiveness was EDTA greater than barbital greater than tryptophan greater than histidine greater than lysine greater than other amino acids. Glycine, Tris and urea were ineffective competitors of p-MB inhibition. Double reciprocal plots showed that the Km for glucose-6-phosphate was increased and the Vmax reduced in the presence of p-MB. HgCl2 was a more effective inhibitor than p-MB with a Ki of 6 X 10(-6) M. We conclude that a reaction of p-MB with M2 sulfhydryls does not play a part in the inhibition of enzyme activity. It is suggested that p-MB may interact with one or more amino acid side chains in such a way that enzyme conformation is altered."}
{"id": "PMID:184376", "title": "The action of insulin and dibutyryl cyclic AMP on the biosynthesis of polyunsaturated acids of alpha-linolenic acid family in HTC cells.", "content": "Incubation of HTC cells (7288 C) with 114C-alpha-linolenic acid in Swim's 77 medium during 24 hours converted the fatty acid to octadeca-6,9,12,15-tetraenoic acid, eicosa-11,14,17-trienoic acid, eicosa-8,11,14,17-tetraenoic acid, eicosa-5,11,14,17-tetraenoic acid, eicosa-5,8,11,14,17-pentaenoic acid and unsaturated acids of 22 carbons. The existence of two pathways was recognized: one initiated by a delta6-desaturation and the other by an elongation of alpha-linolenic acid. Incubation of the cells with insulin and dibutyryl cyclic AMP modified both pathways in different ways. HTC cells were sensitive to insulin which enhanced the desaturating route increasing eicosapentaenoic acid synthesis and depressed the elongating route decreasing eicosatrienoic acid. In an opposite way, dibutyryl cyclic AMP decreased eicosapentaenoic acid synthesis and increased eicosatrienoic acid.", "contents": "The action of insulin and dibutyryl cyclic AMP on the biosynthesis of polyunsaturated acids of alpha-linolenic acid family in HTC cells. Incubation of HTC cells (7288 C) with 114C-alpha-linolenic acid in Swim's 77 medium during 24 hours converted the fatty acid to octadeca-6,9,12,15-tetraenoic acid, eicosa-11,14,17-trienoic acid, eicosa-8,11,14,17-tetraenoic acid, eicosa-5,11,14,17-tetraenoic acid, eicosa-5,8,11,14,17-pentaenoic acid and unsaturated acids of 22 carbons. The existence of two pathways was recognized: one initiated by a delta6-desaturation and the other by an elongation of alpha-linolenic acid. Incubation of the cells with insulin and dibutyryl cyclic AMP modified both pathways in different ways. HTC cells were sensitive to insulin which enhanced the desaturating route increasing eicosapentaenoic acid synthesis and depressed the elongating route decreasing eicosatrienoic acid. In an opposite way, dibutyryl cyclic AMP decreased eicosapentaenoic acid synthesis and increased eicosatrienoic acid."}
{"id": "PMID:184377", "title": "[Treatment of primary hyperlipoproteinemias. Comparison of N 041 with clofibrate].", "content": "The effect of essential phospholipids in combination with Clofibrate (N 041) was compared with that of Clofibrate alone in a double blind study in 96 patients with hypertriglyceridemia and/or hypercholesterolemia. The serum triglycerides fell more markedly with N 041 than with Clofibrate therapy alone. The greater cholesterol-lowering effect of N 041 was significant after treatment lasting 3 weeks and just failed to reach the 5% significance level after 6 weeks. Both preparations were well tolerated.", "contents": "[Treatment of primary hyperlipoproteinemias. Comparison of N 041 with clofibrate]. The effect of essential phospholipids in combination with Clofibrate (N 041) was compared with that of Clofibrate alone in a double blind study in 96 patients with hypertriglyceridemia and/or hypercholesterolemia. The serum triglycerides fell more markedly with N 041 than with Clofibrate therapy alone. The greater cholesterol-lowering effect of N 041 was significant after treatment lasting 3 weeks and just failed to reach the 5% significance level after 6 weeks. Both preparations were well tolerated."}
{"id": "PMID:184380", "title": "Mutagenesis by simian virus 40. I. detection of mutations in Chinese hamster cell lines using different resistance markers.", "content": "The mutagenic action of SV40 in permanent lines of Chinese hamster cells (CHO-K1 and V79) was investigated with the aid of different resistance markers. The markers studied had resistance to 8-azaguanine (25 and 30 mug/ml), aminopterin (3.3--5.5X10(-3) mug/ml), colchicine (6.5 and 7.0X10(-2) mug/ml) and 5-bromodeoxyuridine (50--120 mug/ml), respectively. After virus infection the mutation frequencies were increased by one (azaguanine, aminopterin) and two (colchicine) orders of magnitude as compared with spontaneous mutation frequencies. In contrast, it was not possible to enhance the frequency of mutation to BUdR resistance. On the other hand, the ability to proliferate in HAT medium was induced in three of five BUdR-resistant cell clones by infection with SV40. The resistance induced by SV40 was stable when isolated clones were cultured under non-selective conditions. Mechanisms are proposed that may be responsible for the mutagenic action of SV40.", "contents": "Mutagenesis by simian virus 40. I. detection of mutations in Chinese hamster cell lines using different resistance markers. The mutagenic action of SV40 in permanent lines of Chinese hamster cells (CHO-K1 and V79) was investigated with the aid of different resistance markers. The markers studied had resistance to 8-azaguanine (25 and 30 mug/ml), aminopterin (3.3--5.5X10(-3) mug/ml), colchicine (6.5 and 7.0X10(-2) mug/ml) and 5-bromodeoxyuridine (50--120 mug/ml), respectively. After virus infection the mutation frequencies were increased by one (azaguanine, aminopterin) and two (colchicine) orders of magnitude as compared with spontaneous mutation frequencies. In contrast, it was not possible to enhance the frequency of mutation to BUdR resistance. On the other hand, the ability to proliferate in HAT medium was induced in three of five BUdR-resistant cell clones by infection with SV40. The resistance induced by SV40 was stable when isolated clones were cultured under non-selective conditions. Mechanisms are proposed that may be responsible for the mutagenic action of SV40."}
{"id": "PMID:184381", "title": "Studies on chemically induced dominant lethality. II. Cytogenetic studies of MMS-induced dominant lethality in maturing dictyate mouse oocytes.", "content": "Young adult female mice were injected intravenously with either 50- or 100- mg/kg doses of methyl methanesulfonate. The females were superovulated and mated to untreated males at intervals ranging from 0.5 to 14.5 days after treatment. The fertilized ova were collected and cultured to the first cleavage mitosis, at which time the female chromosome complement was analyzed for structural chromosomal damage. Chromatid-type aberrations were observed, but at a much lower frequency than previously reported for treatment of post-meiotic male germ cells. The time after treatment at which chromosomal damage was observed and the frequency of affected cells agree, qualitatively, with existing dominant-lethal data derived from treatment of maturing oocytes. Parallel experiments in which metaphase I oocytes were analyzed indicate a lack of MMS-induced chromosomal damage in the meiotic stages. This observation is consistent with the suggestion that an intervening round of DNA synthesis is necessary for MMS-induced lesions to be translated into chromosomal damage. The low yield of chromosomal damage is consistent with the idea that maturing oocytes, unlike later spermatids and spermatozoa, are capable of performing macromolecular repair of premutational lesions.", "contents": "Studies on chemically induced dominant lethality. II. Cytogenetic studies of MMS-induced dominant lethality in maturing dictyate mouse oocytes. Young adult female mice were injected intravenously with either 50- or 100- mg/kg doses of methyl methanesulfonate. The females were superovulated and mated to untreated males at intervals ranging from 0.5 to 14.5 days after treatment. The fertilized ova were collected and cultured to the first cleavage mitosis, at which time the female chromosome complement was analyzed for structural chromosomal damage. Chromatid-type aberrations were observed, but at a much lower frequency than previously reported for treatment of post-meiotic male germ cells. The time after treatment at which chromosomal damage was observed and the frequency of affected cells agree, qualitatively, with existing dominant-lethal data derived from treatment of maturing oocytes. Parallel experiments in which metaphase I oocytes were analyzed indicate a lack of MMS-induced chromosomal damage in the meiotic stages. This observation is consistent with the suggestion that an intervening round of DNA synthesis is necessary for MMS-induced lesions to be translated into chromosomal damage. The low yield of chromosomal damage is consistent with the idea that maturing oocytes, unlike later spermatids and spermatozoa, are capable of performing macromolecular repair of premutational lesions."}
{"id": "PMID:184383", "title": "Concentration of 3', 5' cyclic adenosine monophosphate in ventricular cerebrospinal fluid of patients with prolonged coma after head trauma or intracranial hemorrhage.", "content": "A previous study showed that cerebrospinal fluid from the lateral ventricle of patients without disturbance of sensorium or intracranial pressure contains 15 to 30 nm 3', 5' cyclic adenosine monophosphate. We measured the concentration of this cyclic nucleotide by radioimmunoassay in cerebrospinal fluid from the lateral ventricle of six patients with prolonged coma (20 days or longer) after head trauma (four), or spontaneous intracranial hemorrhage (two). Coma was graded IV to I in order of decreasing severity. Fluid was removed at intervals of six to 72 hours from a Rickham reservoir placed in the lateral ventricle. Concentration of the cyclic nucleotide (mean +/- S.E.M.) in coma of Grades IV, III, II and I was 2.1 +/- 0.3, 4.6 +/- 0.5, 6.3 +/- 1.4 and 12.5 +/- 2.4 nM respectively. After sensorium became normal, cAMP was 21.0 +/- 1.4 nM. Correlation between grade of coma and concentration was -0.89 (P less than 0.01). Thus, prolonged coma appears to be associated with a disturbance of cyclic AMP metabolism within the central nervous system.", "contents": "Concentration of 3', 5' cyclic adenosine monophosphate in ventricular cerebrospinal fluid of patients with prolonged coma after head trauma or intracranial hemorrhage. A previous study showed that cerebrospinal fluid from the lateral ventricle of patients without disturbance of sensorium or intracranial pressure contains 15 to 30 nm 3', 5' cyclic adenosine monophosphate. We measured the concentration of this cyclic nucleotide by radioimmunoassay in cerebrospinal fluid from the lateral ventricle of six patients with prolonged coma (20 days or longer) after head trauma (four), or spontaneous intracranial hemorrhage (two). Coma was graded IV to I in order of decreasing severity. Fluid was removed at intervals of six to 72 hours from a Rickham reservoir placed in the lateral ventricle. Concentration of the cyclic nucleotide (mean +/- S.E.M.) in coma of Grades IV, III, II and I was 2.1 +/- 0.3, 4.6 +/- 0.5, 6.3 +/- 1.4 and 12.5 +/- 2.4 nM respectively. After sensorium became normal, cAMP was 21.0 +/- 1.4 nM. Correlation between grade of coma and concentration was -0.89 (P less than 0.01). Thus, prolonged coma appears to be associated with a disturbance of cyclic AMP metabolism within the central nervous system."}
{"id": "PMID:184384", "title": "Big renin and biosynthetic defect of aldosterone in diabetes mellitus.", "content": "To determine the cause of selective aldosterone deficiency in two patients with diabetes mellitus, studies of renin and of aldosterone-precursor metabolites were performed under conditions of sodium depletion and ACTH stimulation. Plasma renin concentration was elevated in both patients, and stimulated plasma renin activity was low in one and normal in the other. Fractionation of plasma extracts demonstrated the presence of \"big renin,\" a relatively inactive precursor of renin. Metabolites of aldosterone precursors were increased, suggesting deficient 18-hydroxylase in one patient and dehydrogenase in the other. The results suggest that hypoaldosteronism in diabetic patients may result from combined defects in both renin and aldosterone biosynthesis.", "contents": "Big renin and biosynthetic defect of aldosterone in diabetes mellitus. To determine the cause of selective aldosterone deficiency in two patients with diabetes mellitus, studies of renin and of aldosterone-precursor metabolites were performed under conditions of sodium depletion and ACTH stimulation. Plasma renin concentration was elevated in both patients, and stimulated plasma renin activity was low in one and normal in the other. Fractionation of plasma extracts demonstrated the presence of \"big renin,\" a relatively inactive precursor of renin. Metabolites of aldosterone precursors were increased, suggesting deficient 18-hydroxylase in one patient and dehydrogenase in the other. The results suggest that hypoaldosteronism in diabetic patients may result from combined defects in both renin and aldosterone biosynthesis."}
{"id": "PMID:184390", "title": "Leydig-cell agenesis: a cause of male pseudohermaphroditism.", "content": "We studied a 35-year-old patient with female external genitalia, primary amenorrhea and XY karytotype. Plasma testosterone was 10 ng per deciliter, which did not change after administration of human chorionic gonadotropin, increased to 22 ng per deciliter after ACTH, and decreased to 0.9 ng per deciliter after dexamethasone. Plasma delta 4-androstenedione, dehydroepiandrosterone and 17-hydroxyprogesterone were in the normal range. Plasma luteinizing hormone was high, but follicle-stimulating hormone normal (7.5 mlU per milliliter). There were two testes with epididymis and vas deferens, but no Mullerian structures. Microscopical examination showed hyalinization of tubules, which were lined by normal Sertoli cells and occasional immature germ cells. No Leydig cells were seen. After castration follicle-stimulating hormone increased to 43 mlU per milliliter. We conclude that this case of male pseudohermaphroditism was probably due to a Leydig-cell agenesis, that the epididymis and vas deferens can be developed in such a condition and the follicle-stimulating hormone secretion is regulated, at least in part, by a non-androgen substance secreted by Sertoli cells.", "contents": "Leydig-cell agenesis: a cause of male pseudohermaphroditism. We studied a 35-year-old patient with female external genitalia, primary amenorrhea and XY karytotype. Plasma testosterone was 10 ng per deciliter, which did not change after administration of human chorionic gonadotropin, increased to 22 ng per deciliter after ACTH, and decreased to 0.9 ng per deciliter after dexamethasone. Plasma delta 4-androstenedione, dehydroepiandrosterone and 17-hydroxyprogesterone were in the normal range. Plasma luteinizing hormone was high, but follicle-stimulating hormone normal (7.5 mlU per milliliter). There were two testes with epididymis and vas deferens, but no Mullerian structures. Microscopical examination showed hyalinization of tubules, which were lined by normal Sertoli cells and occasional immature germ cells. No Leydig cells were seen. After castration follicle-stimulating hormone increased to 43 mlU per milliliter. We conclude that this case of male pseudohermaphroditism was probably due to a Leydig-cell agenesis, that the epididymis and vas deferens can be developed in such a condition and the follicle-stimulating hormone secretion is regulated, at least in part, by a non-androgen substance secreted by Sertoli cells."}
{"id": "PMID:184391", "title": "Correction of leukocyte function in Chediak-Higashi syndrome by ascorbate.", "content": "Because ascorbate potentiates chemotaxis of normal leukocytes, we examined the effect of ascorbate on polymorphonuclear leukocytes from a patient with the Chediak-Higashi syndrome. Chemotactic migration was 104+/-16 leukocytes per 10 fields (mean+/-S.D.) initially and 258+/-44 (P less than 0.001) after ascorbate, as compared to 182+/-10 in controls. There was no bactericidal activity by 40 minutes in the patient's untreated leukocytes. After ascorbate bactericidal activity of patient and untreated control cells was the same. The addition of ascorbate reduced cAMP levels in the patient's cells from a mean of 34.5 pmoles per 10(7) polymorphonuclear leukocytes to 5.9, as compared to a control value of 3.1+/-1.4. The association of elevated cAMP and impaired function in the polymorphonuclear leukocytes of patients with the Chediak-Higashi syndrome may be related to abnormal microtubular assembly.", "contents": "Correction of leukocyte function in Chediak-Higashi syndrome by ascorbate. Because ascorbate potentiates chemotaxis of normal leukocytes, we examined the effect of ascorbate on polymorphonuclear leukocytes from a patient with the Chediak-Higashi syndrome. Chemotactic migration was 104+/-16 leukocytes per 10 fields (mean+/-S.D.) initially and 258+/-44 (P less than 0.001) after ascorbate, as compared to 182+/-10 in controls. There was no bactericidal activity by 40 minutes in the patient's untreated leukocytes. After ascorbate bactericidal activity of patient and untreated control cells was the same. The addition of ascorbate reduced cAMP levels in the patient's cells from a mean of 34.5 pmoles per 10(7) polymorphonuclear leukocytes to 5.9, as compared to a control value of 3.1+/-1.4. The association of elevated cAMP and impaired function in the polymorphonuclear leukocytes of patients with the Chediak-Higashi syndrome may be related to abnormal microtubular assembly."}
{"id": "PMID:184406", "title": "Effects of norgestrel and metyrapone on pituitary-adrenal-ovarian function.", "content": "To assess the effects of d-norgestrel on pituitary-adrenal-ovarian function, basal levels and responses to metyrapone of urinary 17-ketogenic steroids (17-KGS) and 17-ketosteroids (17-KS), plasma cortisol (F), plasma delta4-androstenedione (A), plasma testosterone (T), plasma estrone (E1) and estradiol (E2), plasma and urinary LH and FSH were determined in 10 normal women before and while taking d-norgestrel 1 mg/day. Cortisol secretion rate (CSR) and binding capacities of cortisol binding globulin (CBG) and testosterone-estradiol binding globulin (TeBG) were also measured. Norgestrel did not significantly alter 17-KGS, 17-KS, F, LH, FSH, CSR, or the 17-KGS and 17-KS responses to metyrapone. Norgestrel reduced TeBG binding capacity but not CBG binding capacity. Norgestrel competitively inhibited the binding of dihydrotestosterone to TeBG under in vitro conditions. Levels of T, E2, and E1 were reduced by norgestrel. All measured hormone levels except FSH were increased following metyrapone prior to norgestrel administration. Norgestrel completely blocked the metyrapone-induced increases in LH and E2 and markedly reduced the E1 increase. Metyrapone reduced E2 during norgestrel treatment.", "contents": "Effects of norgestrel and metyrapone on pituitary-adrenal-ovarian function. To assess the effects of d-norgestrel on pituitary-adrenal-ovarian function, basal levels and responses to metyrapone of urinary 17-ketogenic steroids (17-KGS) and 17-ketosteroids (17-KS), plasma cortisol (F), plasma delta4-androstenedione (A), plasma testosterone (T), plasma estrone (E1) and estradiol (E2), plasma and urinary LH and FSH were determined in 10 normal women before and while taking d-norgestrel 1 mg/day. Cortisol secretion rate (CSR) and binding capacities of cortisol binding globulin (CBG) and testosterone-estradiol binding globulin (TeBG) were also measured. Norgestrel did not significantly alter 17-KGS, 17-KS, F, LH, FSH, CSR, or the 17-KGS and 17-KS responses to metyrapone. Norgestrel reduced TeBG binding capacity but not CBG binding capacity. Norgestrel competitively inhibited the binding of dihydrotestosterone to TeBG under in vitro conditions. Levels of T, E2, and E1 were reduced by norgestrel. All measured hormone levels except FSH were increased following metyrapone prior to norgestrel administration. Norgestrel completely blocked the metyrapone-induced increases in LH and E2 and markedly reduced the E1 increase. Metyrapone reduced E2 during norgestrel treatment."}
{"id": "PMID:184407", "title": "Myoepithelioma. Review of the literature and report of a case with ultrastructural confirmation.", "content": "The myoepithelioma is a rare salivary gland tumor composed nearly exclusively of myoepithelial cells. A case occurring on the palate of a 22-year-old man is reported. Electron microscopic findings of occasional desmosomes, a basal lamina associated with the plasma memb;rane, and perinuclear cytoplasmic filaments confirmed the diagnosis. The myoepithelioma appears to resemble the pleomorphic adenoma clinically and may be a development variant of the pleomorphic adenoma.", "contents": "Myoepithelioma. Review of the literature and report of a case with ultrastructural confirmation. The myoepithelioma is a rare salivary gland tumor composed nearly exclusively of myoepithelial cells. A case occurring on the palate of a 22-year-old man is reported. Electron microscopic findings of occasional desmosomes, a basal lamina associated with the plasma memb;rane, and perinuclear cytoplasmic filaments confirmed the diagnosis. The myoepithelioma appears to resemble the pleomorphic adenoma clinically and may be a development variant of the pleomorphic adenoma."}
{"id": "PMID:184408", "title": "The implantation of natural tooth form bioglasses in baboons. A preliminary report.", "content": "This report describes a 6-month screening study comparing the tissue responses of several bioglass natural tooth implants in adult female baboons. The dental implants were designed to elicit osteogenesis at the interface of the implant and the oral tissues. This is in contrast to those types of implant materials that are merely biologically acceptable. Incisor teeth were extracted, dupplicated in bioglass, returned to the natural sockets, and splinted to the adjacent natural tooth, where they remained splinted for 3 months and then free standing for an additional 3 months. Microscopic evaluation revealed distinct histopathologic characteristics with certain  bioglass formulas, such as ankylosis, a pseudofibrous capsule with fibers running parallel to the root surface, or an apparently true periodontal membrane with properly oriented Sharpey's fibers. True cementogenesis was not found.", "contents": "The implantation of natural tooth form bioglasses in baboons. A preliminary report. This report describes a 6-month screening study comparing the tissue responses of several bioglass natural tooth implants in adult female baboons. The dental implants were designed to elicit osteogenesis at the interface of the implant and the oral tissues. This is in contrast to those types of implant materials that are merely biologically acceptable. Incisor teeth were extracted, dupplicated in bioglass, returned to the natural sockets, and splinted to the adjacent natural tooth, where they remained splinted for 3 months and then free standing for an additional 3 months. Microscopic evaluation revealed distinct histopathologic characteristics with certain  bioglass formulas, such as ankylosis, a pseudofibrous capsule with fibers running parallel to the root surface, or an apparently true periodontal membrane with properly oriented Sharpey's fibers. True cementogenesis was not found."}
{"id": "PMID:184409", "title": "Abnormal tooth tissue in human odontodysplasia.", "content": "The affected teeth in this case of odontodysplasia exhibited abnormal hypoplastic enamel, abnormal dentin containing extensive interglobular regions and completely lacking a peritubular matrix, and an abnormal irregular tissue consisting of highly calcified and partially fused granules located within the dentin of the tooth tips. Electron micrographs of the irregular tissue showed that the granules consisted of crystallites densely and radically packed in a noncollagenous amorphous matrix. Granules were surrounded by a slightly calcified, irregularly arranged, collagenous matrix. The irregular tissue formed in the pulp of the tooth tip befofe and independently of the dentin. It was at least partially formed by pulpal calcification. Abnormal dentin matrix was formed by odontoblasts which were less differentiated than normal. Odontodysplastic teeth showed abnormal differentiation of odontoblasts and ameloblasts resulting in defective enamel and dentin and, in extreme cases, in extensive pulpal calcification.", "contents": "Abnormal tooth tissue in human odontodysplasia. The affected teeth in this case of odontodysplasia exhibited abnormal hypoplastic enamel, abnormal dentin containing extensive interglobular regions and completely lacking a peritubular matrix, and an abnormal irregular tissue consisting of highly calcified and partially fused granules located within the dentin of the tooth tips. Electron micrographs of the irregular tissue showed that the granules consisted of crystallites densely and radically packed in a noncollagenous amorphous matrix. Granules were surrounded by a slightly calcified, irregularly arranged, collagenous matrix. The irregular tissue formed in the pulp of the tooth tip befofe and independently of the dentin. It was at least partially formed by pulpal calcification. Abnormal dentin matrix was formed by odontoblasts which were less differentiated than normal. Odontodysplastic teeth showed abnormal differentiation of odontoblasts and ameloblasts resulting in defective enamel and dentin and, in extreme cases, in extensive pulpal calcification."}
{"id": "PMID:184411", "title": "[Pathogenetic investigations on a case of mauriac syndrome (author's transl)].", "content": "The results of clinical and biochemical investigations on a girl with all obligatory signs of Mauriac syndrome already in infancy were compared with the different hypotheses suggested in order to explain the pathogenesis of this disease. One possible explanation for the origin of MS might be a decreased sensitivity of adenylate-cyclase to glucagon or adrenalin. Hypersensitivity to insulin, resulting in a decreased production of cyclic AMP and activation of glycogen synthetase could be excluded by measuring the urine excretion of cAMP with and without insulin. Furthermore no signs of dyspituarism were detectable on our case and the hypothesis of MS being a combination of primary glycogenosis and diabetes mellitus could also be refuted. Liver enzyme activities were normal.", "contents": "[Pathogenetic investigations on a case of mauriac syndrome (author's transl)]. The results of clinical and biochemical investigations on a girl with all obligatory signs of Mauriac syndrome already in infancy were compared with the different hypotheses suggested in order to explain the pathogenesis of this disease. One possible explanation for the origin of MS might be a decreased sensitivity of adenylate-cyclase to glucagon or adrenalin. Hypersensitivity to insulin, resulting in a decreased production of cyclic AMP and activation of glycogen synthetase could be excluded by measuring the urine excretion of cAMP with and without insulin. Furthermore no signs of dyspituarism were detectable on our case and the hypothesis of MS being a combination of primary glycogenosis and diabetes mellitus could also be refuted. Liver enzyme activities were normal."}
{"id": "PMID:184412", "title": "Neoplasia in the rat induced by N-hydroxyphenacetin, a metabolite of phenacetin.", "content": "N-hydroxyphenacetin, a phenacetin metabolite, was fed to rats as a 0.05-0.5% dietary supplement. After 9 months, tumours of the liver were found in 36 of 64 animals. One animal also developed a renal tumour. No tumours were found in control animals. The findings implicate phenacetin as a carcinogen and suggest that N-hydroxyphenacetin may be the metabolite responsible.", "contents": "Neoplasia in the rat induced by N-hydroxyphenacetin, a metabolite of phenacetin. N-hydroxyphenacetin, a phenacetin metabolite, was fed to rats as a 0.05-0.5% dietary supplement. After 9 months, tumours of the liver were found in 36 of 64 animals. One animal also developed a renal tumour. No tumours were found in control animals. The findings implicate phenacetin as a carcinogen and suggest that N-hydroxyphenacetin may be the metabolite responsible."}
{"id": "PMID:184419", "title": "Unusual roentgenological findings in cytomegalic inclusion body disease: large and circumscribed calcareous deposits of the basal ganglia and scattered calcifications of the parieto-occipital cortex.", "content": "The roentgenological and clinical findings of a five year old girl suffering from cytomegalic inclusion body disease are reported. In this disease unusual circumscript and large calcareous deposits of the basal ganglia and scattered gyriform calcifications of the occipito-parietal cortex were shown on plain skull x-rays and their paraventricular localization demonstrated on pneumoencephalotomogram.", "contents": "Unusual roentgenological findings in cytomegalic inclusion body disease: large and circumscribed calcareous deposits of the basal ganglia and scattered calcifications of the parieto-occipital cortex. The roentgenological and clinical findings of a five year old girl suffering from cytomegalic inclusion body disease are reported. In this disease unusual circumscript and large calcareous deposits of the basal ganglia and scattered gyriform calcifications of the occipito-parietal cortex were shown on plain skull x-rays and their paraventricular localization demonstrated on pneumoencephalotomogram."}
{"id": "PMID:184420", "title": "The incipient Wilms' tumor.", "content": "The diagnosis of Wilms' tumor is usually made by excretory urography after the patient presents with an abdominal mass. A diagnosis prior to the appearance of an obvious mass might result in an improved cure rate and less morbid therapy. The three cases described illustrate the difficulty in making an earlier diagnosis since pyelograms were \"normal\" prior to detection of the abdominal mass.", "contents": "The incipient Wilms' tumor. The diagnosis of Wilms' tumor is usually made by excretory urography after the patient presents with an abdominal mass. A diagnosis prior to the appearance of an obvious mass might result in an improved cure rate and less morbid therapy. The three cases described illustrate the difficulty in making an earlier diagnosis since pyelograms were \"normal\" prior to detection of the abdominal mass."}
{"id": "PMID:184421", "title": "Bilateral nephroblastomatosis.", "content": "Bilateral nephromegaly with a histological picture of diffuse Wilms' tumor or so-called bilateral nephroblastomatosis is a rare condition. We present an additional case documented by urography. To our knowledge, this is the first report of diffuse nephroblastomatosis recognized at 2 hours of age. A few cases are reported but urographic documentation is available in only 4 of those and in our own. The review of the urographic findings reveals features which seem seem to be nearly pathognomonic of this condition. Urographic appearance similar to that of adult type polycystic disease without the typical radiolucent cysts, should raise the suspicion of a diffuse bilateral process in the kidneys. Exclusion of other infiltrative diseases, like leukemia and glycogen storage disease, should lead to radiologic diagnosis of nephroblastomatosis. Renal biopsy is then indicated.", "contents": "Bilateral nephroblastomatosis. Bilateral nephromegaly with a histological picture of diffuse Wilms' tumor or so-called bilateral nephroblastomatosis is a rare condition. We present an additional case documented by urography. To our knowledge, this is the first report of diffuse nephroblastomatosis recognized at 2 hours of age. A few cases are reported but urographic documentation is available in only 4 of those and in our own. The review of the urographic findings reveals features which seem seem to be nearly pathognomonic of this condition. Urographic appearance similar to that of adult type polycystic disease without the typical radiolucent cysts, should raise the suspicion of a diffuse bilateral process in the kidneys. Exclusion of other infiltrative diseases, like leukemia and glycogen storage disease, should lead to radiologic diagnosis of nephroblastomatosis. Renal biopsy is then indicated."}
{"id": "PMID:184422", "title": "Segmental embryonic peripheral neuropathy.", "content": "Based on a new interpretation of the radiology, the author has proposed the hypothesis that reduction deformities of the limbs are of sensory neuropathic origin. This hypothesis is examined in terms of the segmental sensory innervation of the skeleton. The predicted effect of sclerotome subtraction is compared with the radiological malformations, and is found to support the hypothesis.", "contents": "Segmental embryonic peripheral neuropathy. Based on a new interpretation of the radiology, the author has proposed the hypothesis that reduction deformities of the limbs are of sensory neuropathic origin. This hypothesis is examined in terms of the segmental sensory innervation of the skeleton. The predicted effect of sclerotome subtraction is compared with the radiological malformations, and is found to support the hypothesis."}
{"id": "PMID:184423", "title": "Metastatic neonatal Wilms' tumor: a case report with review of the literature.", "content": "An unusual case of congenital Wilms' tumor is discussed. Although the very existence of neonatal Wilms' has been challenged, this case represents a well documented example, rendered all the more unusual by concurrent metastatic disease and a second primary malignancy in the posterior fossa.", "contents": "Metastatic neonatal Wilms' tumor: a case report with review of the literature. An unusual case of congenital Wilms' tumor is discussed. Although the very existence of neonatal Wilms' has been challenged, this case represents a well documented example, rendered all the more unusual by concurrent metastatic disease and a second primary malignancy in the posterior fossa."}
{"id": "PMID:184425", "title": "The effect of premature delivery on the development of gluconeogenic enzymes in the guinea pig.", "content": "The activities of key gluconeogenic enzymes in the livers of newborn guinea pigs were monitored as a function of time following birth either vaginally at term or prematurely by cesarian section at 62 days of gestation. The activity of hepatic glucose-6-phosphatase rose dramatically from 1.40 +/- 0.26 mumol/min/g at birth to a maximum of 6.8 +/- 0.9 mumol/min/g at 24 hr in prematurely delivered animals although there was little significant change in activity in full term animals. The activity of hepatic fructose-1,6-diphosphatase and mitochondrial phosphoenolpyruvate carboxykinase changed little over the first 3 days of life in either full term or premature animals. Cytosolic phosphoenolpyruvate carboxykinase, on the other hand, had low activity at birth being 0.11 +/- 0.03 mumol/min/g in full term and 0.06 +/- 0.04 mumol in premature animals rising to values of 0.71 +/- 0.06 and 1.12 +/- 0.12 mumol/min/g, respectively, at 24 hr of life. Pyruvate carboxylase activities in the premature animals remained significantly lower than those in full term animals in the first 72 hr of life. Transient hypoglycemia was evident in the prematurely delivered animals, but not in the full term animals, the blood glucose values being 82 +/- 7 mg/100 ml for the full term animals and 20 +/- 8 mg/100 ml for the premature infants at 2 hr of life.", "contents": "The effect of premature delivery on the development of gluconeogenic enzymes in the guinea pig. The activities of key gluconeogenic enzymes in the livers of newborn guinea pigs were monitored as a function of time following birth either vaginally at term or prematurely by cesarian section at 62 days of gestation. The activity of hepatic glucose-6-phosphatase rose dramatically from 1.40 +/- 0.26 mumol/min/g at birth to a maximum of 6.8 +/- 0.9 mumol/min/g at 24 hr in prematurely delivered animals although there was little significant change in activity in full term animals. The activity of hepatic fructose-1,6-diphosphatase and mitochondrial phosphoenolpyruvate carboxykinase changed little over the first 3 days of life in either full term or premature animals. Cytosolic phosphoenolpyruvate carboxykinase, on the other hand, had low activity at birth being 0.11 +/- 0.03 mumol/min/g in full term and 0.06 +/- 0.04 mumol in premature animals rising to values of 0.71 +/- 0.06 and 1.12 +/- 0.12 mumol/min/g, respectively, at 24 hr of life. Pyruvate carboxylase activities in the premature animals remained significantly lower than those in full term animals in the first 72 hr of life. Transient hypoglycemia was evident in the prematurely delivered animals, but not in the full term animals, the blood glucose values being 82 +/- 7 mg/100 ml for the full term animals and 20 +/- 8 mg/100 ml for the premature infants at 2 hr of life."}
{"id": "PMID:184426", "title": "Lactic acidosis in three sibs due to defects in both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes.", "content": "A Canadian Indian family is described in which three of the children were mentally retarded, and had seizures and other neurological abnormalities. They had chronic metabolic acidosis associated with elevated blood levels of lactate, pyruvate, and alanine. Two of the children excreted large amounts of pyruvic and alpha-ketoglutaric acids in the urine and had elevated plasma levels of glutamic acid and proline. Hypoglycemia occurred with fasting in two of the children. Treatment with pharmacological doses of thiamine, lipoic acid, biotin, riboflavin, and various dietary regimes was without effect. One child died at 3 1/2 months and another at 4 1/2 months; the third is still alive at 23 months of age. Enzyme assays revealed a low level of activity of both the pyruvate and alpha-ketoglutarate dehydrogenase complexes in cultured fibroblasts of one of the sibs. These patients appeared to have partial defects in the oxidation of pyruvate, as well as of alpha-ketoglutarate within the tricarboxylic acid cycle.", "contents": "Lactic acidosis in three sibs due to defects in both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes. A Canadian Indian family is described in which three of the children were mentally retarded, and had seizures and other neurological abnormalities. They had chronic metabolic acidosis associated with elevated blood levels of lactate, pyruvate, and alanine. Two of the children excreted large amounts of pyruvic and alpha-ketoglutaric acids in the urine and had elevated plasma levels of glutamic acid and proline. Hypoglycemia occurred with fasting in two of the children. Treatment with pharmacological doses of thiamine, lipoic acid, biotin, riboflavin, and various dietary regimes was without effect. One child died at 3 1/2 months and another at 4 1/2 months; the third is still alive at 23 months of age. Enzyme assays revealed a low level of activity of both the pyruvate and alpha-ketoglutarate dehydrogenase complexes in cultured fibroblasts of one of the sibs. These patients appeared to have partial defects in the oxidation of pyruvate, as well as of alpha-ketoglutarate within the tricarboxylic acid cycle."}
{"id": "PMID:184428", "title": "Neoplasia of early life and its relationships to teratogenesis.", "content": "The biologic peculiarities of tumors of early life are elucidated. The oncogenic grace period is emphasized, wherein infantile tumors tend to behave in a relatively benign fashion up until 3-6 months of age. A review of the types of congenital malformations associated with the development of neoplasms is presented. These associations appear to be of fundamental importance in developmental pathobiology. They are illustrated by the tendency for neoplasms to develop in anomalous or dysplastic tissues, such as developmental vestiges, undescended testes, dysgenic gonads and certain hamartoses. There is an increased incidence of tumor occurrence in: (1) specific teratologic disorders: aniridia, hemihypertrophy, Beckwith's syndrome, basal cell nevus syndromes and others; (2) cytogenetic abnormalities: Down's syndrome, 13q- syndrome (D-deletion), trisomy 18; (3) chromosomal instability syndromes: Fanconi's anemia, ataxia-telangiectasia, Bloom's syndrome. Finally, many agents, known to be carcinogenic when administered postnatally to animals, are teratogenic in the fetus. A few agents--urethan, alkylnitrosoureas, estrogens--are both teratogenic and carcinogenic when administered to the fetus transplacentally. It is suggested that the timing of intrauterine insult is important in determining whether the effect on the offspring is teratogenic, oncogenic or both. Teratogenesis appears to be the more primitive response. Other theories explaining the concurrence of tumors and anomalies are offered.", "contents": "Neoplasia of early life and its relationships to teratogenesis. The biologic peculiarities of tumors of early life are elucidated. The oncogenic grace period is emphasized, wherein infantile tumors tend to behave in a relatively benign fashion up until 3-6 months of age. A review of the types of congenital malformations associated with the development of neoplasms is presented. These associations appear to be of fundamental importance in developmental pathobiology. They are illustrated by the tendency for neoplasms to develop in anomalous or dysplastic tissues, such as developmental vestiges, undescended testes, dysgenic gonads and certain hamartoses. There is an increased incidence of tumor occurrence in: (1) specific teratologic disorders: aniridia, hemihypertrophy, Beckwith's syndrome, basal cell nevus syndromes and others; (2) cytogenetic abnormalities: Down's syndrome, 13q- syndrome (D-deletion), trisomy 18; (3) chromosomal instability syndromes: Fanconi's anemia, ataxia-telangiectasia, Bloom's syndrome. Finally, many agents, known to be carcinogenic when administered postnatally to animals, are teratogenic in the fetus. A few agents--urethan, alkylnitrosoureas, estrogens--are both teratogenic and carcinogenic when administered to the fetus transplacentally. It is suggested that the timing of intrauterine insult is important in determining whether the effect on the offspring is teratogenic, oncogenic or both. Teratogenesis appears to be the more primitive response. Other theories explaining the concurrence of tumors and anomalies are offered."}
{"id": "PMID:184429", "title": "The nephroblastomatosis complex and its relationship to Wilms' tumor: a clinicopathologic treatise.", "content": "1. At least one third of all children with Wilms' tumors have evidence of aberrant metanephric differentiation, hamartomas, adenomas and nodules of blastema or Wilms' tumorlets in the subcapsular renal cortex. Only the presence of nodular renal blastema was found to correlate with younger age, suggesting that the other tumorlike lesions may be derivatives. 2. In our experience, all patients with bilateral and sequential bilateral Wilms' tumors have exhibited these characteristics in the \"uninvolved\" renal tissue removed at nephrectomy. 3. Pancortical (infantile), diffuse superficial (late infantile) and multifocal (juvenile) variants of nephroblastomatosis are defined. In the latter 2 forms of nephroblastomatosis the prognosis after modern therapy is at least as good as it is in patients with unilateral, unicentric Wilms' tumor arising in a histologically normal kidney. 4. The morphologic evidence presented strongly indicates that Wilms' tumor in patients with nephroblastomatosis develops either from nodular blastema or metanephric hamartomas. It is hypothetically possible that all Wilms' tumors develop from these precursors. The latent period between cessation of nephrogenesis and clinical presentation of Wilms' tumor is interpreted as favoring the hypothesis that carcinogenesis per se is the result of a postnatal event but that the substrate for tumor development, aberrant metanephric proliferation, has its inception during gestation.", "contents": "The nephroblastomatosis complex and its relationship to Wilms' tumor: a clinicopathologic treatise. 1. At least one third of all children with Wilms' tumors have evidence of aberrant metanephric differentiation, hamartomas, adenomas and nodules of blastema or Wilms' tumorlets in the subcapsular renal cortex. Only the presence of nodular renal blastema was found to correlate with younger age, suggesting that the other tumorlike lesions may be derivatives. 2. In our experience, all patients with bilateral and sequential bilateral Wilms' tumors have exhibited these characteristics in the \"uninvolved\" renal tissue removed at nephrectomy. 3. Pancortical (infantile), diffuse superficial (late infantile) and multifocal (juvenile) variants of nephroblastomatosis are defined. In the latter 2 forms of nephroblastomatosis the prognosis after modern therapy is at least as good as it is in patients with unilateral, unicentric Wilms' tumor arising in a histologically normal kidney. 4. The morphologic evidence presented strongly indicates that Wilms' tumor in patients with nephroblastomatosis develops either from nodular blastema or metanephric hamartomas. It is hypothetically possible that all Wilms' tumors develop from these precursors. The latent period between cessation of nephrogenesis and clinical presentation of Wilms' tumor is interpreted as favoring the hypothesis that carcinogenesis per se is the result of a postnatal event but that the substrate for tumor development, aberrant metanephric proliferation, has its inception during gestation."}
{"id": "PMID:184433", "title": "[Adult Niemann-Pick disease: a 26 years follow-up. Report of a case with isolated visceral involvement, excess of tissue sphingomyelin, and deficient sphingomyelinase activity (author's transl)].", "content": "The case report of Niemann-Pick disease, in a 26 years old woman whose first symptoms appeared when she was 17 months old, is described. The disease, involving considerable hepatosplenomegaly and pulmonary infiltration, was diagnosed by the presence of lipid laden macrophages (resembling foam cells, sea blue histiocytes and kidney intermediate forms) in the bone marrow, liver and kidney, and an excess of tissue sphingomyelin and cholesterol, and a decrease in sphingomyelinase in circulating leucocytes. The results of ultrastructural, histochemical and biochemical studies on hepatic and renal lipids are reported. The relationship of the case to the sea blue histiocyte syndrome is discussed.", "contents": "[Adult Niemann-Pick disease: a 26 years follow-up. Report of a case with isolated visceral involvement, excess of tissue sphingomyelin, and deficient sphingomyelinase activity (author's transl)]. The case report of Niemann-Pick disease, in a 26 years old woman whose first symptoms appeared when she was 17 months old, is described. The disease, involving considerable hepatosplenomegaly and pulmonary infiltration, was diagnosed by the presence of lipid laden macrophages (resembling foam cells, sea blue histiocytes and kidney intermediate forms) in the bone marrow, liver and kidney, and an excess of tissue sphingomyelin and cholesterol, and a decrease in sphingomyelinase in circulating leucocytes. The results of ultrastructural, histochemical and biochemical studies on hepatic and renal lipids are reported. The relationship of the case to the sea blue histiocyte syndrome is discussed."}
{"id": "PMID:184435", "title": "\"Fingerprinting\" high molecular weight RNA by two-dimensional gel electrophoresis: application to poliovirus RNA.", "content": "Conditions are described under which complete RNase T1 digests of high molecular weight RNA can be separated into numerous components by two-dimensional gel electrophoresis. Small and large oligonucleotides (n = 1 - 2c0) can be resolved without losses. The procedure yields fingerprints which are diagnostic for a particular species of RNA and an index of its purity as will be shown for the genomes of poliovirus type 1 and 2.", "contents": "\"Fingerprinting\" high molecular weight RNA by two-dimensional gel electrophoresis: application to poliovirus RNA. Conditions are described under which complete RNase T1 digests of high molecular weight RNA can be separated into numerous components by two-dimensional gel electrophoresis. Small and large oligonucleotides (n = 1 - 2c0) can be resolved without losses. The procedure yields fingerprints which are diagnostic for a particular species of RNA and an index of its purity as will be shown for the genomes of poliovirus type 1 and 2."}
{"id": "PMID:184436", "title": "Reduced DNA repair in mouse satellite DNA after treatment with methylmethanesulfonate, and N-methyl-N-nitrosourea.", "content": "We have measured DNA repair in mouse satellite and main band DNA as resolved by Ag+-Cs2SO4 centrifugation in response to treatment with the alkylating agents, methyl methanesulfonate, and N-methyl-N-nitrosourea. We find that there is a statistically significant lower incorporation of 3H-Tdr into the satellite DNA as compared to the main band at varying periods after treatment with the alkylating agents. This suggests a reduced repair activity in the satellite DNA. We have measured the extent of binding of 14C-methyl methanesulfonate to the satellite, and main band DNA, and no difference in binding was observed, indicating that the reduced repair activity of satellite DNA is not due to a difference in binding of alkylating agents. We believe that the reduced incorporation of 3H-Tdr into satellite DNA may be due to its location in the condensed chromatin fraction.", "contents": "Reduced DNA repair in mouse satellite DNA after treatment with methylmethanesulfonate, and N-methyl-N-nitrosourea. We have measured DNA repair in mouse satellite and main band DNA as resolved by Ag+-Cs2SO4 centrifugation in response to treatment with the alkylating agents, methyl methanesulfonate, and N-methyl-N-nitrosourea. We find that there is a statistically significant lower incorporation of 3H-Tdr into the satellite DNA as compared to the main band at varying periods after treatment with the alkylating agents. This suggests a reduced repair activity in the satellite DNA. We have measured the extent of binding of 14C-methyl methanesulfonate to the satellite, and main band DNA, and no difference in binding was observed, indicating that the reduced repair activity of satellite DNA is not due to a difference in binding of alkylating agents. We believe that the reduced incorporation of 3H-Tdr into satellite DNA may be due to its location in the condensed chromatin fraction."}
{"id": "PMID:184437", "title": "Conformational analysis of polynucleotides. I. The favorable left-handed helical model for the poly(8,2'-S-cycloadenylic acid) with high anti conformation.", "content": "1) Energy calculations have shown that poly (8,2'-S-cycloadenylic aicd) can form left-handed helices owing to the high anti conformation. 2) Two favorable left-handed helices are characterized by axial translation per residue (Z=4.3 and 3.6A) and by rotations per residue (theta= 40 degrees and -25 degrees). 3) The proposed helical models might be stable in aqueous solution and is well explicable of the optical property of this compound.", "contents": "Conformational analysis of polynucleotides. I. The favorable left-handed helical model for the poly(8,2'-S-cycloadenylic acid) with high anti conformation. 1) Energy calculations have shown that poly (8,2'-S-cycloadenylic aicd) can form left-handed helices owing to the high anti conformation. 2) Two favorable left-handed helices are characterized by axial translation per residue (Z=4.3 and 3.6A) and by rotations per residue (theta= 40 degrees and -25 degrees). 3) The proposed helical models might be stable in aqueous solution and is well explicable of the optical property of this compound."}
{"id": "PMID:184438", "title": "Minichromosome of simian virus 40: presence of histone HI.", "content": "In contrast to conclusions of previous studies /I-3/ claiming the absence of histone HI from the SV40 and polyoma viral minichromosomes we have found that a preparation of purified SV40 minichromosomes does contain histone HI. The content of HI in relation to other four histones in the SV40 minichromosomes is close to that in the cellular chromatin. Histone HI in the isolated SV40 minichromosomes is bound apparently to internucleosomal DNA stretches as was shown already for HI in the cellular chromatin /4/. In addition it was found that more than 90% of the purified SV40 minichromosomes migrated as a single discrete deoxyribonucleoprotein band upon agarose gel electrophoresis.", "contents": "Minichromosome of simian virus 40: presence of histone HI. In contrast to conclusions of previous studies /I-3/ claiming the absence of histone HI from the SV40 and polyoma viral minichromosomes we have found that a preparation of purified SV40 minichromosomes does contain histone HI. The content of HI in relation to other four histones in the SV40 minichromosomes is close to that in the cellular chromatin. Histone HI in the isolated SV40 minichromosomes is bound apparently to internucleosomal DNA stretches as was shown already for HI in the cellular chromatin /4/. In addition it was found that more than 90% of the purified SV40 minichromosomes migrated as a single discrete deoxyribonucleoprotein band upon agarose gel electrophoresis."}
{"id": "PMID:184439", "title": "Satellite DNA sequence content of polylysine-titratable and nuclease-resistant fractions of mouse liver hepatoma chromatin.", "content": "Micrococcal nuclease digestion of mouse TLT liver hepatoma chromatin proceeds rapidly to the point where approximately 35% of the DNA is recoverable by centrifugation of the chromatin DNA through 3M CsCl. The satellite DNA sequence content of this recoverable DNA is the same as whole chromatin DNA (10%). The 11s (penultimate digestion product) monomer, as well as intermediate multiples and relatively undigested large chromatin segments are separable on steep hlycerol gradients. The DNA isolated from these fractions also contains the normal 10% satellite DNA content. Progressive polylysine titration of chromatin followed by nuclease digestion gives anomalous recoveries of DNA but, nonetheless, the satellite sequence content titration of chromatin, followed by pronase and then nuclease digestion, again gave recoverable DNA with a satellite sequence content of 10%. These results are discussed in terms of the conclusion that nucleosome (or upsilon-body) structures are distributed in a random fashion over the genome.", "contents": "Satellite DNA sequence content of polylysine-titratable and nuclease-resistant fractions of mouse liver hepatoma chromatin. Micrococcal nuclease digestion of mouse TLT liver hepatoma chromatin proceeds rapidly to the point where approximately 35% of the DNA is recoverable by centrifugation of the chromatin DNA through 3M CsCl. The satellite DNA sequence content of this recoverable DNA is the same as whole chromatin DNA (10%). The 11s (penultimate digestion product) monomer, as well as intermediate multiples and relatively undigested large chromatin segments are separable on steep hlycerol gradients. The DNA isolated from these fractions also contains the normal 10% satellite DNA content. Progressive polylysine titration of chromatin followed by nuclease digestion gives anomalous recoveries of DNA but, nonetheless, the satellite sequence content titration of chromatin, followed by pronase and then nuclease digestion, again gave recoverable DNA with a satellite sequence content of 10%. These results are discussed in terms of the conclusion that nucleosome (or upsilon-body) structures are distributed in a random fashion over the genome."}
{"id": "PMID:184448", "title": "Preparation of subcellular fractions from rat liver: comparison of the Polytron with the Dounce homogenizer.", "content": "The PolytronR and Dounce homogenizers have been evaluated for preparation of homogenates of rat liver prior to isolation of subcellular fractions by differential centrifugation. Marker enzymes used to evaluate the subcellular fractions included cytochrome oxidase, monoamine oxidase, D-amino acid oxidase, acid phosphatase, glucose-6-phosphatase, ethyl morphine demethylase, and lactate dehydrogenase. No significant difference in the distribution of enzymes (percent recovery or specific activity) was observed between the two methods of homogenization. In addition, there were no significant differences in the ultrastructural appearances and respiratory control ratios of the mitochondrial fractions prepared by the two methods of homogenization.", "contents": "Preparation of subcellular fractions from rat liver: comparison of the Polytron with the Dounce homogenizer. The PolytronR and Dounce homogenizers have been evaluated for preparation of homogenates of rat liver prior to isolation of subcellular fractions by differential centrifugation. Marker enzymes used to evaluate the subcellular fractions included cytochrome oxidase, monoamine oxidase, D-amino acid oxidase, acid phosphatase, glucose-6-phosphatase, ethyl morphine demethylase, and lactate dehydrogenase. No significant difference in the distribution of enzymes (percent recovery or specific activity) was observed between the two methods of homogenization. In addition, there were no significant differences in the ultrastructural appearances and respiratory control ratios of the mitochondrial fractions prepared by the two methods of homogenization."}
{"id": "PMID:184452", "title": "Metalloprotein electron transfer reactions: analysis of reactivity of horse heart cytochrome c with inorganic complexes.", "content": "The reactions of horse heart cytochrome c with Fe(ethylenediaminetetraacetate)2-, Co(1,10-phenanthroline)3(3+), Ru(NH3)6(2+), and Fe(CN)6(3-) have been analyzed within the formalism of the Marcus theory of outer-sphere electron transfer, including compensation for electrostatic interactions. Calculated protein self-exchange rate constants based on crossreactions are found to vary over three orders of magnitude, decreasing according to Fe(CN)6(3-) greater than Ru(NH3)6(2+) greater than Fe(EDTA)2-. The reactivity order suggests that the mechanism of electron transfer involves attack by the small molecule reagents near the most nearly exposed region of the heme; this attack is affected by electrostatic interactions with the positively charged protein, by hydrophobic interactions that permit reagent penetration of the protein surface, and by the availability of pi symmetry ligand (or extended metal) orbitals that can overlap with the pi redox orbitals of the heme group.", "contents": "Metalloprotein electron transfer reactions: analysis of reactivity of horse heart cytochrome c with inorganic complexes. The reactions of horse heart cytochrome c with Fe(ethylenediaminetetraacetate)2-, Co(1,10-phenanthroline)3(3+), Ru(NH3)6(2+), and Fe(CN)6(3-) have been analyzed within the formalism of the Marcus theory of outer-sphere electron transfer, including compensation for electrostatic interactions. Calculated protein self-exchange rate constants based on crossreactions are found to vary over three orders of magnitude, decreasing according to Fe(CN)6(3-) greater than Ru(NH3)6(2+) greater than Fe(EDTA)2-. The reactivity order suggests that the mechanism of electron transfer involves attack by the small molecule reagents near the most nearly exposed region of the heme; this attack is affected by electrostatic interactions with the positively charged protein, by hydrophobic interactions that permit reagent penetration of the protein surface, and by the availability of pi symmetry ligand (or extended metal) orbitals that can overlap with the pi redox orbitals of the heme group."}
{"id": "PMID:184453", "title": "Adenosine 3':5'-cyclic monophosphate deficiency in Neurospora crassa.", "content": "Depending on growth conditions, the adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels of the fr mutant, a morphologically aberrant strain of Neurospora crassa, are reduced 2- to 5-fold. By taking advantage of the differences in phenotype of fr in liquid and agar cultures and the positive response of fr grown on solid support to exogenous theophylline, a relationship between the degree of morphological abnormality and intracellular cyclic AMP levels of the mutant is observed. Progressive restoration of the fr phenotype toward a normal state is paralleled by increases in cyclic nucleotide content. Striking differences in the sedimentation and thermal characteristics of the fr and wild-type adenylate cyclases [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] are observed. Approximately 50% of the normal activity sediments at 105,000 X g compared to 5% of the mutant enzyme. In addition, the overall stability of the fr adenylate cyclase is significantly decreased and its rate of inactivation at 37 degrees in the absence of substrate is 10-fold greater than the wild-type adenylate cyclase. Arrhenius plots also indicated that the Q10 (increase in rate per 10 degrees temperature increase) and the temperature of maximal activity of the fr enzyme are reduced. Supplementation of fr agar cultures with linolenic acid results in an elevated cyclic AMP content and a wild-type-like morphology similar to that obtained with inhibitors of phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17). An increased thermostability of the fr adenylate cyclase occurs on linolenate enrichment of the mutant. It is concluded that the cyclic AMP deficiency is at least partially responsible for the fr phenotype and that this reduction results from a membrane defect that affects adenylate cyclase function.", "contents": "Adenosine 3':5'-cyclic monophosphate deficiency in Neurospora crassa. Depending on growth conditions, the adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels of the fr mutant, a morphologically aberrant strain of Neurospora crassa, are reduced 2- to 5-fold. By taking advantage of the differences in phenotype of fr in liquid and agar cultures and the positive response of fr grown on solid support to exogenous theophylline, a relationship between the degree of morphological abnormality and intracellular cyclic AMP levels of the mutant is observed. Progressive restoration of the fr phenotype toward a normal state is paralleled by increases in cyclic nucleotide content. Striking differences in the sedimentation and thermal characteristics of the fr and wild-type adenylate cyclases [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] are observed. Approximately 50% of the normal activity sediments at 105,000 X g compared to 5% of the mutant enzyme. In addition, the overall stability of the fr adenylate cyclase is significantly decreased and its rate of inactivation at 37 degrees in the absence of substrate is 10-fold greater than the wild-type adenylate cyclase. Arrhenius plots also indicated that the Q10 (increase in rate per 10 degrees temperature increase) and the temperature of maximal activity of the fr enzyme are reduced. Supplementation of fr agar cultures with linolenic acid results in an elevated cyclic AMP content and a wild-type-like morphology similar to that obtained with inhibitors of phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17). An increased thermostability of the fr adenylate cyclase occurs on linolenate enrichment of the mutant. It is concluded that the cyclic AMP deficiency is at least partially responsible for the fr phenotype and that this reduction results from a membrane defect that affects adenylate cyclase function."}
{"id": "PMID:184454", "title": "Identification of enzyme-bound activated CO2 as carbonic-phosphoric anhydride: isolation of the corresponding trimethyl derivative from the active site of glutamine-dependent carbamyl phosphate synthetase.", "content": "The activated CO2 intermediate formed in the reaction catalyzed by glutamine-dependent carbamyl phosphate synthetase was identified as carbonic-phosphoric anhydride through the use of two independent procedures. The carboxy phosphate intermediate was reduced to formate by treatment with potassium borohydride. Although both free CO2 and the enzyme-bound activated CO2 are reduced to formic acid by borohydride, it was possible to selectively introduce a 14C label into the enzyme-bound activated CO2 and thus into the formic acid derived from it. Such [14C]formate formation required the presence of ATP, KCl, and the enzyme, and evidence was obtained that the [14C]formate found is not derived from carbamyl phosphate or from bicarbonate bound nonspecifically to the enzyme. When the enzyme was treated with L-2-amino-4-oxo-5-chloropentanoate (or cyanate), the formation of [14C]formate was increased about 2-fold, a finding consistent with the previous observation that such treatment effects a similar increase in the bicarbonate-dependent cleavage of ATP catalyzed by the enzyme. When reaction mixtures containing the enzyme, [gamma-32P]ATP, and [14C]bicarbonate were methylated by treatment with diazomethane, a labeled compound was formed which cochromatographed with authentic trimethyl carboxy phosphate. Equimolar quantities of 14C and 32P wer incorporated into the intermediate, thus confirming its identification as carboxy phosphate. Nonenzymatic transphosphorylation from ATP to bicarbonate to form carboxy phosphate was also detected by diazomethane trapping.", "contents": "Identification of enzyme-bound activated CO2 as carbonic-phosphoric anhydride: isolation of the corresponding trimethyl derivative from the active site of glutamine-dependent carbamyl phosphate synthetase. The activated CO2 intermediate formed in the reaction catalyzed by glutamine-dependent carbamyl phosphate synthetase was identified as carbonic-phosphoric anhydride through the use of two independent procedures. The carboxy phosphate intermediate was reduced to formate by treatment with potassium borohydride. Although both free CO2 and the enzyme-bound activated CO2 are reduced to formic acid by borohydride, it was possible to selectively introduce a 14C label into the enzyme-bound activated CO2 and thus into the formic acid derived from it. Such [14C]formate formation required the presence of ATP, KCl, and the enzyme, and evidence was obtained that the [14C]formate found is not derived from carbamyl phosphate or from bicarbonate bound nonspecifically to the enzyme. When the enzyme was treated with L-2-amino-4-oxo-5-chloropentanoate (or cyanate), the formation of [14C]formate was increased about 2-fold, a finding consistent with the previous observation that such treatment effects a similar increase in the bicarbonate-dependent cleavage of ATP catalyzed by the enzyme. When reaction mixtures containing the enzyme, [gamma-32P]ATP, and [14C]bicarbonate were methylated by treatment with diazomethane, a labeled compound was formed which cochromatographed with authentic trimethyl carboxy phosphate. Equimolar quantities of 14C and 32P wer incorporated into the intermediate, thus confirming its identification as carboxy phosphate. Nonenzymatic transphosphorylation from ATP to bicarbonate to form carboxy phosphate was also detected by diazomethane trapping."}
{"id": "PMID:184455", "title": "Competition between cellular and viral mRNAs in vitro is regulated by a messenger discriminatory initiation factor.", "content": "Encephalomyocarditis viral RNA has previously been shown to outcompete host cellular mRNA has for translation in vitro in crude and fractionated protein synthesizing systems. In the present communication it is shown that the competition is regulated by an initiation factor or complex of factors, and not the 40S initiation complex per se. The factor primarily involved is the murine equivalent of a component present in a partially purified preparation of rabbit initiation factor M3. Both the murine and rabbit factors are clearly messenger discriminatory.", "contents": "Competition between cellular and viral mRNAs in vitro is regulated by a messenger discriminatory initiation factor. Encephalomyocarditis viral RNA has previously been shown to outcompete host cellular mRNA has for translation in vitro in crude and fractionated protein synthesizing systems. In the present communication it is shown that the competition is regulated by an initiation factor or complex of factors, and not the 40S initiation complex per se. The factor primarily involved is the murine equivalent of a component present in a partially purified preparation of rabbit initiation factor M3. Both the murine and rabbit factors are clearly messenger discriminatory."}
{"id": "PMID:184456", "title": "Importance of the third amino acid residue of oxytocin for its action on isolated rat uterus: study of relationship between hormone conformation and activity.", "content": "In a continued effort to relate the three-dimensional structure of a peptide hormone to its biological activity, the dose-response relationships of [3-phenylalanine] oxytocin (oxypressin), with an aromatic amino acid residue in position 3, and [3-beta-cyclohexylalanine]oxytocin, with an aliphatic amino acid residue to position 3, were determined in the rat uterine assay in vitro and compared to that of oxytocin. Oxypressin has not only a lower affinity for the smooth muscle receptor than the natural hormone, but also a decreased maximal response (efficacy). [3-beta-Cyclohexylalanine]oxytocin exhibits an even lower affinity than oxypressin, but retains the same maximal response as oxytocin. A reorientation of the tyrosine sidechain, caused by the presence of a neighboring aromatic sidechain in position 3, away from the surface of the 20-membered ring is though to remove the phenolic hydroxyl group from its optimal position in the \"active center\" of oxytocin and give rise to the reduced efficacy of oxypressin.", "contents": "Importance of the third amino acid residue of oxytocin for its action on isolated rat uterus: study of relationship between hormone conformation and activity. In a continued effort to relate the three-dimensional structure of a peptide hormone to its biological activity, the dose-response relationships of [3-phenylalanine] oxytocin (oxypressin), with an aromatic amino acid residue in position 3, and [3-beta-cyclohexylalanine]oxytocin, with an aliphatic amino acid residue to position 3, were determined in the rat uterine assay in vitro and compared to that of oxytocin. Oxypressin has not only a lower affinity for the smooth muscle receptor than the natural hormone, but also a decreased maximal response (efficacy). [3-beta-Cyclohexylalanine]oxytocin exhibits an even lower affinity than oxypressin, but retains the same maximal response as oxytocin. A reorientation of the tyrosine sidechain, caused by the presence of a neighboring aromatic sidechain in position 3, away from the surface of the 20-membered ring is though to remove the phenolic hydroxyl group from its optimal position in the \"active center\" of oxytocin and give rise to the reduced efficacy of oxypressin."}
{"id": "PMID:184457", "title": "Fate of mismatched base-pair regions in polyoma heteroduplex DNA during infection of mouse cells.", "content": "Heteroduplex DNA has been constructed from two variants of polyoma virus that differ genotypically at four distinct sites. The genotypes of the progeny virus derived from infections of mouse cells with single heteroduplexes have been analyzed to determine how the genotypic markers of the parental heteroduplex segregate. Markers that are separated by a length of DNA greater than 600 nucleotides segregate independently. Segregation was not detected between two markers separated by only approximately 90 nucleotides. We interpret these results on the basis of the correction of mismatched base-pair regions in the heteroduplex before the completion of DNA replication. We suggest that this technique provides valuable information concerning gene conversion in mamalian cells and permits the transfer of genotypic markers from one virus strain to another.", "contents": "Fate of mismatched base-pair regions in polyoma heteroduplex DNA during infection of mouse cells. Heteroduplex DNA has been constructed from two variants of polyoma virus that differ genotypically at four distinct sites. The genotypes of the progeny virus derived from infections of mouse cells with single heteroduplexes have been analyzed to determine how the genotypic markers of the parental heteroduplex segregate. Markers that are separated by a length of DNA greater than 600 nucleotides segregate independently. Segregation was not detected between two markers separated by only approximately 90 nucleotides. We interpret these results on the basis of the correction of mismatched base-pair regions in the heteroduplex before the completion of DNA replication. We suggest that this technique provides valuable information concerning gene conversion in mamalian cells and permits the transfer of genotypic markers from one virus strain to another."}
{"id": "PMID:184458", "title": "Specificity of the protein kinase activity associated with the hemin-controlled repressor of rabbit reticulocyte.", "content": "Highly purified preparations of hemin-controlled repressor of rabbit reticulocyte contain a 3':5'-cyclic AMP-indenpendent protein kinase activity that phosphorylates the low-molecular-weight (about 38,000) polypeptide chain of the initiation factor that forms a ternary complex with GTP and Met-tRNAf. These preparations also phosphorylate several polypeptide components of reticulocyte 40S ribosomal subunits. However, no significant levels of phosphorylation are observed when casein, histones, Artemia salina 40S ribosomal subunits, or other initiation factor fractions are used as substrates although high levels of phosphorylation are obtained with cruder preparations of the repressor. An antibody to these highly purified preparations of repressor has been obtained from the serum of immunized goats. Preincubation with immune goat IgG results in the neutralization of the inhibitory activity of the repressor, while normal IgG has no effect. Preincubation with immune IgG also abolishes the protein kinase activity responsible for the phosphorylation of the initiation factor and reticulocyte 40S subunits. Histone phosphorylation by crude repressor preparations, on the other hand, is unaffected by preincubation with immune IgG.", "contents": "Specificity of the protein kinase activity associated with the hemin-controlled repressor of rabbit reticulocyte. Highly purified preparations of hemin-controlled repressor of rabbit reticulocyte contain a 3':5'-cyclic AMP-indenpendent protein kinase activity that phosphorylates the low-molecular-weight (about 38,000) polypeptide chain of the initiation factor that forms a ternary complex with GTP and Met-tRNAf. These preparations also phosphorylate several polypeptide components of reticulocyte 40S ribosomal subunits. However, no significant levels of phosphorylation are observed when casein, histones, Artemia salina 40S ribosomal subunits, or other initiation factor fractions are used as substrates although high levels of phosphorylation are obtained with cruder preparations of the repressor. An antibody to these highly purified preparations of repressor has been obtained from the serum of immunized goats. Preincubation with immune goat IgG results in the neutralization of the inhibitory activity of the repressor, while normal IgG has no effect. Preincubation with immune IgG also abolishes the protein kinase activity responsible for the phosphorylation of the initiation factor and reticulocyte 40S subunits. Histone phosphorylation by crude repressor preparations, on the other hand, is unaffected by preincubation with immune IgG."}
{"id": "PMID:184459", "title": "Autoregulation of simian virus 40 gene A by T antigen.", "content": "During lytic infection by simian virus 40, gene A is transcribed into early RNA, which is translated into A protein (T antigen). Both the rate of synthesis and the intracellular amount of early RNA are higher in cells infected by temperature-sensitive A (tsA) mutants than in cells infected by wild-type virus. These differences are observed at permissive temperature (32 degrees) and are amplified greatly after a shift to restrictive temperature (41 degrees). For example, at 32 degrees cells infected by tsA mutants synthesize early RNA approximately twice as fast as cells infected by wild-type virus. After the shift to 41 degrees, the rate of synthesis in the tsA infection increases to 15 times the rate in the wild-type infection. In contrast, cells infected by tsA mutants do not overproduce late RNA. We suggest that the A protein regulates its own synthesis by negative feedback control of gene A transcription.", "contents": "Autoregulation of simian virus 40 gene A by T antigen. During lytic infection by simian virus 40, gene A is transcribed into early RNA, which is translated into A protein (T antigen). Both the rate of synthesis and the intracellular amount of early RNA are higher in cells infected by temperature-sensitive A (tsA) mutants than in cells infected by wild-type virus. These differences are observed at permissive temperature (32 degrees) and are amplified greatly after a shift to restrictive temperature (41 degrees). For example, at 32 degrees cells infected by tsA mutants synthesize early RNA approximately twice as fast as cells infected by wild-type virus. After the shift to 41 degrees, the rate of synthesis in the tsA infection increases to 15 times the rate in the wild-type infection. In contrast, cells infected by tsA mutants do not overproduce late RNA. We suggest that the A protein regulates its own synthesis by negative feedback control of gene A transcription."}
{"id": "PMID:184460", "title": "Regulation of protein synthesis in reticulocyte lysates: phosphorylation of methionyl-tRNAf binding factor by protein kinase activity of translational inhibitor isolated from hemedeficient lysates.", "content": "A previous study demonstrated that the translational inhibitor from lysates of heme-deficient rabbit reticulocytes is associated with a protein kinase activity. Chromatography of this inhibitor preparation on phosphocellulose yields two distinct protein kinase activities, PC1 and PC2. PC1, which consitutes about 90% of the activity in the unresolved preparation, does not inhibit protein synthesis in lysates, but actively phosporylates calf thymus histone II in a 3':5'-cyclic AMP-denpendent reaction. PC2 contains the translational inhibitor, phosphorylates histone poorly, and is not cyclic AMP-dependent. While [gamma-32P]ATP as the phosphate donor, the two kinase fractions were analyzed with the putative substrates, salt-washed 40S ribosomal subunits, and the initiation factor that mediates the binding of Met-tRNAf to the 40S subunit. PC1 is inactive with the initiation factor, but phosphorylates 40S subunits at a single major site that migrates as a 31,000-dalton band in sodium dodecyl sulfate-acrylamide gels; phosphorylation requires cyclic AMP. Similar phosphorylation of the reticulocyte 40S site (31,000 daltons) can be demonstrated with other cyclic AMP-dependent kinases from reticulocytes, rat liver, and bovine heart muscle. PC2 phosphorylates the small subunit (38,000 daltons) but not the large subunit(s) of the initiation factor; the reaction does not require cyclic AMP. PC2 does not phosphorylate 40S subunits. In the presence of 40S subunits, the initiation factor appears to be rapidly bound in a manner that effectively blocks phosphorylation of the initiation factor by PC2; under the same conditions phosphorylation of the 40S subunit by PC1 is not affected. The initiation factor has been shown to reverse the inhibitions of protein chain initiation induced in lysates by heme deficiency, double-stranded RNA, oxidized glutathione, or the purified translational inhibitor. The observation that the Met-tRNAf binding factor is phosphorylated by PC2 supports the hypothesis that this initiation factor is a target for the action of the translational inhibitor activated in heme deficiency.", "contents": "Regulation of protein synthesis in reticulocyte lysates: phosphorylation of methionyl-tRNAf binding factor by protein kinase activity of translational inhibitor isolated from hemedeficient lysates. A previous study demonstrated that the translational inhibitor from lysates of heme-deficient rabbit reticulocytes is associated with a protein kinase activity. Chromatography of this inhibitor preparation on phosphocellulose yields two distinct protein kinase activities, PC1 and PC2. PC1, which consitutes about 90% of the activity in the unresolved preparation, does not inhibit protein synthesis in lysates, but actively phosporylates calf thymus histone II in a 3':5'-cyclic AMP-denpendent reaction. PC2 contains the translational inhibitor, phosphorylates histone poorly, and is not cyclic AMP-dependent. While [gamma-32P]ATP as the phosphate donor, the two kinase fractions were analyzed with the putative substrates, salt-washed 40S ribosomal subunits, and the initiation factor that mediates the binding of Met-tRNAf to the 40S subunit. PC1 is inactive with the initiation factor, but phosphorylates 40S subunits at a single major site that migrates as a 31,000-dalton band in sodium dodecyl sulfate-acrylamide gels; phosphorylation requires cyclic AMP. Similar phosphorylation of the reticulocyte 40S site (31,000 daltons) can be demonstrated with other cyclic AMP-dependent kinases from reticulocytes, rat liver, and bovine heart muscle. PC2 phosphorylates the small subunit (38,000 daltons) but not the large subunit(s) of the initiation factor; the reaction does not require cyclic AMP. PC2 does not phosphorylate 40S subunits. In the presence of 40S subunits, the initiation factor appears to be rapidly bound in a manner that effectively blocks phosphorylation of the initiation factor by PC2; under the same conditions phosphorylation of the 40S subunit by PC1 is not affected. The initiation factor has been shown to reverse the inhibitions of protein chain initiation induced in lysates by heme deficiency, double-stranded RNA, oxidized glutathione, or the purified translational inhibitor. The observation that the Met-tRNAf binding factor is phosphorylated by PC2 supports the hypothesis that this initiation factor is a target for the action of the translational inhibitor activated in heme deficiency."}
{"id": "PMID:184461", "title": "Incorporation of adenosine into ATP: formation of compartmentalized ATP.", "content": "The incorporation of [3H]adenosine, [3H]adenine, and [3H]hypoxanthine into adenine nucleotides of nude (athymic) mouse liver and human hepatoma grown subcutaneously in nude mice was studied. 3H and 32P radioactive labeling in vivo of acid-soluble nucleotides followed by chromatographic procedures indicated that, in contrast to [3H]adenine and [3H]hypoxanthine, [3H]adenosine is preferentially incorporated into ATP in comparison with its incorporation into AMP and ADP. This phenomenon, as well as complementing the recently reported 3-fold increase in total cellular ATP upon treatmen- with 0.5-1.0 mM concentrations of adenosine, indicates the formation from adenosine of compartmentalized ATP that is not produced from either adenine or hypoxanthine. The observed effect is of larger magnitude in the growth-arrested normal liver than in the actively growing tumor.", "contents": "Incorporation of adenosine into ATP: formation of compartmentalized ATP. The incorporation of [3H]adenosine, [3H]adenine, and [3H]hypoxanthine into adenine nucleotides of nude (athymic) mouse liver and human hepatoma grown subcutaneously in nude mice was studied. 3H and 32P radioactive labeling in vivo of acid-soluble nucleotides followed by chromatographic procedures indicated that, in contrast to [3H]adenine and [3H]hypoxanthine, [3H]adenosine is preferentially incorporated into ATP in comparison with its incorporation into AMP and ADP. This phenomenon, as well as complementing the recently reported 3-fold increase in total cellular ATP upon treatmen- with 0.5-1.0 mM concentrations of adenosine, indicates the formation from adenosine of compartmentalized ATP that is not produced from either adenine or hypoxanthine. The observed effect is of larger magnitude in the growth-arrested normal liver than in the actively growing tumor."}
{"id": "PMID:184462", "title": "Covalent modification of proteins by metabolites of NAD+.", "content": "Covalently bound adducts of ply(L-lysine), bovine serum albumin, lysine rich histone (f1) and deoxyribonucleotidase I (DNase, EC 3.1.4.5) with adenosine diphosphoribose and ribose-5-phosphate were prepared at pH 7.4 and 9.5. Macromolecular adducts of bovine serum albumin and histone (f1) were isolated by gel filtration and electrophoresis. Reduction of products by NaBH4 did not dissociate the ribose-5-phosphate moiety from macromolecules. Specific introduction of 3H into the adducts also indicated Schiff base formation. The reaction of ribose-5-phosphate with epsilon-amino groups of histone (f1) approached 70-90% saturation. Spermine and spermidine also react with adenosine diphosphoribose and ribose-5-phosphate to form 1:1 Schiff bases. It is proposed that high turnover of cellular NAD+ is the source of aldehydic metabolites which may regulate macromolecular metabolism by covalent modification of nuclear proteins, whereas polyamines serve as modulators of this control cycle.", "contents": "Covalent modification of proteins by metabolites of NAD+. Covalently bound adducts of ply(L-lysine), bovine serum albumin, lysine rich histone (f1) and deoxyribonucleotidase I (DNase, EC 3.1.4.5) with adenosine diphosphoribose and ribose-5-phosphate were prepared at pH 7.4 and 9.5. Macromolecular adducts of bovine serum albumin and histone (f1) were isolated by gel filtration and electrophoresis. Reduction of products by NaBH4 did not dissociate the ribose-5-phosphate moiety from macromolecules. Specific introduction of 3H into the adducts also indicated Schiff base formation. The reaction of ribose-5-phosphate with epsilon-amino groups of histone (f1) approached 70-90% saturation. Spermine and spermidine also react with adenosine diphosphoribose and ribose-5-phosphate to form 1:1 Schiff bases. It is proposed that high turnover of cellular NAD+ is the source of aldehydic metabolites which may regulate macromolecular metabolism by covalent modification of nuclear proteins, whereas polyamines serve as modulators of this control cycle."}
{"id": "PMID:184463", "title": "Interferon-induced inhibition of protein synthesis in L-cell extracts: an ATP-dependent step in the activation of an inhibitor by double-stranded RNA.", "content": "The translation of encephalomyocarditis virion RNA in extracts from interferon-treated L-cells is inhibited by the addition of double-stranded RNA (dsRNA) at 400 ng/ml. A similar inhibition in response to dsRNA is seen in control cell extracts supplemented with small amounts of a postribosomal supernatant fraction from interferon-treated cells (interferon cell sap): Neither interferon cell sap nor dsRNA alone is inhibitory in control systems. The inhibition is much reduced if translation is carried out at low ATP concentrations.Conversely, the inhibitory capacity of the interferon cell sap is increased 100-fold if it is preincubated with dsRNA and ATP prior to its addition to the protein-synthesizing system. After this preincubation all detectable dsRNA can be removed without any diminution of the inhibitory activity of the cell sap. These results are compatible with a two-step model for the inhibition in which a pre-inhibitor is activated by dsRNA, the activated inhibitor then interacting with the protein synthesis system to inhibit translation.", "contents": "Interferon-induced inhibition of protein synthesis in L-cell extracts: an ATP-dependent step in the activation of an inhibitor by double-stranded RNA. The translation of encephalomyocarditis virion RNA in extracts from interferon-treated L-cells is inhibited by the addition of double-stranded RNA (dsRNA) at 400 ng/ml. A similar inhibition in response to dsRNA is seen in control cell extracts supplemented with small amounts of a postribosomal supernatant fraction from interferon-treated cells (interferon cell sap): Neither interferon cell sap nor dsRNA alone is inhibitory in control systems. The inhibition is much reduced if translation is carried out at low ATP concentrations.Conversely, the inhibitory capacity of the interferon cell sap is increased 100-fold if it is preincubated with dsRNA and ATP prior to its addition to the protein-synthesizing system. After this preincubation all detectable dsRNA can be removed without any diminution of the inhibitory activity of the cell sap. These results are compatible with a two-step model for the inhibition in which a pre-inhibitor is activated by dsRNA, the activated inhibitor then interacting with the protein synthesis system to inhibit translation."}
{"id": "PMID:184464", "title": "Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts.", "content": "Cultured fibroblasts derived from patients with homozygous familial hypercholesterolemia, which lack functional low density lipoprotein (LDL) receptors, fail to bind, take up, or degrade the lipoprotein with high affinity; therefore LDL-cholesterol is not made available for suppression of cholesterol synthesis or activation of cholesteryl ester formation. When LDL was given a positive charge by reaction with N,N-dimethyl-1,3-propanediamine (cationized LDL), the rate of degradation of the lipoprotein was increased by more than 100-fold in the homozygous familial hypercholesterolemia fibroblasts. Degradation of cationized LDL was inhibited by chloroquine, suggesting that it occurred in cellular lysosomes. Although the cationized LDL entered the cell through a mechanism independent of the LDL receptor, the cholesterol liberated from the degradation of the lipoprotein became available for suppression of cholesterol synthesis and stimulation of cholesteryl ester formation in the homozygous familial hypercholesterolemia fibroblasts. The rate of degradation of albumin by fibroblasts was also increased by more than 100-fold when this protein was coupled to N,N-dimethyl-1,3-propanediamine. The ability to deliver a protein to lysosomes by giving it a strong positive charge may have potential relevance not only to familial hypercholesterolemia, but also to inborn errors of metabolism that involve deficiencies in lysosomal enzymes.", "contents": "Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts. Cultured fibroblasts derived from patients with homozygous familial hypercholesterolemia, which lack functional low density lipoprotein (LDL) receptors, fail to bind, take up, or degrade the lipoprotein with high affinity; therefore LDL-cholesterol is not made available for suppression of cholesterol synthesis or activation of cholesteryl ester formation. When LDL was given a positive charge by reaction with N,N-dimethyl-1,3-propanediamine (cationized LDL), the rate of degradation of the lipoprotein was increased by more than 100-fold in the homozygous familial hypercholesterolemia fibroblasts. Degradation of cationized LDL was inhibited by chloroquine, suggesting that it occurred in cellular lysosomes. Although the cationized LDL entered the cell through a mechanism independent of the LDL receptor, the cholesterol liberated from the degradation of the lipoprotein became available for suppression of cholesterol synthesis and stimulation of cholesteryl ester formation in the homozygous familial hypercholesterolemia fibroblasts. The rate of degradation of albumin by fibroblasts was also increased by more than 100-fold when this protein was coupled to N,N-dimethyl-1,3-propanediamine. The ability to deliver a protein to lysosomes by giving it a strong positive charge may have potential relevance not only to familial hypercholesterolemia, but also to inborn errors of metabolism that involve deficiencies in lysosomal enzymes."}
{"id": "PMID:184465", "title": "Effect of sugars on early biochemical events in development of Dictyostelium discoideum.", "content": "Metabolizable sugars blocked development of the slime mold Dictyostelium discoideum; the same sugars also inhibited the formation of contact sites \"A\", of membranal 3':5'-cyclic adenosine monophosphate (cAMP)-binding sites, and of total cAMP phosphodoesterase (3':5'-cyclic-nucleotide phosphodiesterase; EC 3.1.4.17; 3':5'-cyclic-nucleotide 5'-nucleotidohydrolase). These inhibitory effects of the sugars on the synthesis of cellular components, required for the aggregation of developing amebae, were paralleled by an inhibition of the accumulation of cAMP which normally accompanies development. The inhibition by sugars could be overcome partially by pulsing the amebae with nanomolar concentrations of cAMP only after the amebae had acquired cAMP-binding sites. The findings suggest that metabolizable sugars inhibit development by blocking the formation of cAMP and, conversely, that development in D. discoideum may be related to the energetic state of the cell.", "contents": "Effect of sugars on early biochemical events in development of Dictyostelium discoideum. Metabolizable sugars blocked development of the slime mold Dictyostelium discoideum; the same sugars also inhibited the formation of contact sites \"A\", of membranal 3':5'-cyclic adenosine monophosphate (cAMP)-binding sites, and of total cAMP phosphodoesterase (3':5'-cyclic-nucleotide phosphodiesterase; EC 3.1.4.17; 3':5'-cyclic-nucleotide 5'-nucleotidohydrolase). These inhibitory effects of the sugars on the synthesis of cellular components, required for the aggregation of developing amebae, were paralleled by an inhibition of the accumulation of cAMP which normally accompanies development. The inhibition by sugars could be overcome partially by pulsing the amebae with nanomolar concentrations of cAMP only after the amebae had acquired cAMP-binding sites. The findings suggest that metabolizable sugars inhibit development by blocking the formation of cAMP and, conversely, that development in D. discoideum may be related to the energetic state of the cell."}
{"id": "PMID:184466", "title": "Regulation of tubulin synthesis in islets of Langerhans.", "content": "Tubulin represents a major protein in rat pancreatic islets, which averages 0.5% of the total protein content and 6% of the noninsulin protein synthesized under basal metabolic conditions. Glucose increases the synthesis of tubulin twofold to threefold. Tubulin synthesis is also stimulated by adenosine 3':5'-cyclic monophosphate in both the absence and presence of glucose; this effect of adenosine 3':5'-cyclic monophosphate occurs preferential to noninsulin protein synthesis at physiological glucose concentrations. Tubulin synthesis was decreased more than 75% by fasting, an effect prevented by maintaining animals on glucose exclusively. The fasting-induced reduction in tubulin synthesis is corrected in vitro by increasing adenosine 3':5'-cyclic monophosphate levels. These findings parallel changes previously reported in insulin release and suggest that physiological agents can exert their insulin secretory action through an effect upon the rate of tubulin synthesis.", "contents": "Regulation of tubulin synthesis in islets of Langerhans. Tubulin represents a major protein in rat pancreatic islets, which averages 0.5% of the total protein content and 6% of the noninsulin protein synthesized under basal metabolic conditions. Glucose increases the synthesis of tubulin twofold to threefold. Tubulin synthesis is also stimulated by adenosine 3':5'-cyclic monophosphate in both the absence and presence of glucose; this effect of adenosine 3':5'-cyclic monophosphate occurs preferential to noninsulin protein synthesis at physiological glucose concentrations. Tubulin synthesis was decreased more than 75% by fasting, an effect prevented by maintaining animals on glucose exclusively. The fasting-induced reduction in tubulin synthesis is corrected in vitro by increasing adenosine 3':5'-cyclic monophosphate levels. These findings parallel changes previously reported in insulin release and suggest that physiological agents can exert their insulin secretory action through an effect upon the rate of tubulin synthesis."}
{"id": "PMID:184467", "title": "Control of growth of benzo(a)pyrene-transformed 3T3 cells.", "content": "The growth controls observed in benzo[a]pyrene-transformed 3T3 cells (BP3T3) are compared with those of virus-transformed and normal 3T3 cells. Superficially, the chemically transformed BP3T3 cells have the same behavior as virus-transformed SV3T3 cells. Both grow to high cell density in culture medium with 10% serum, both form colonies in Methocel, and both are tumorigenic. Closer examination, however, has disclosed that BP3T3 cells exhibit \"normal\" growth controls at low serum concentrations. In contrast to the behavior of SV3T3 cells, the initiation of DNA synthesis in BP3T3 cells is still dependent on a serum factor. If BP3T3 cells are grown in medium with 0.2% serum, the cells become quiescent, with growth arrested in the Gu or G0 phase of the cell cycle. The addition of serum or the fibroblast growth factor (FGF) to such quiescent cells leads to the initiation of DNA synthesis and the resumption of growth. As with normal 3T3 cells, if the growth rate of BP3T3 cells is limited by a suboptimal concentration of serum, the growth rate of the cells is increased by the addition of FGF. Also, BP3T3 cells show density-dependent regulation of growth, if the medium contains a low concentration of serum. BP3T3 cells, therefore, have the behavior of \"transformed\" cells when cultured in medium with 10% serum, but behave as \"normal\" cells in medium with low serum. In comparison with normal 3T3 cells, the difference in growth behavior of BP3T3 cells appears to be due to a substantial decrease in the cells' requirement for a serum growth factor of the FGF type. Exploration of possible causes of this substantial decrease indicates that the primary cause is a lower rate of depletion of the serum growth factor from the culture medium by BP3T3 cells. The decrease in rate of depletion is sufficient to account for the uncontrolled growth of BP3T3 cells in medium with 10% serum. It is suggested that a decreased rate of depletion of a growth factor may contribute to tumorigenicity of cells in vivo.", "contents": "Control of growth of benzo(a)pyrene-transformed 3T3 cells. The growth controls observed in benzo[a]pyrene-transformed 3T3 cells (BP3T3) are compared with those of virus-transformed and normal 3T3 cells. Superficially, the chemically transformed BP3T3 cells have the same behavior as virus-transformed SV3T3 cells. Both grow to high cell density in culture medium with 10% serum, both form colonies in Methocel, and both are tumorigenic. Closer examination, however, has disclosed that BP3T3 cells exhibit \"normal\" growth controls at low serum concentrations. In contrast to the behavior of SV3T3 cells, the initiation of DNA synthesis in BP3T3 cells is still dependent on a serum factor. If BP3T3 cells are grown in medium with 0.2% serum, the cells become quiescent, with growth arrested in the Gu or G0 phase of the cell cycle. The addition of serum or the fibroblast growth factor (FGF) to such quiescent cells leads to the initiation of DNA synthesis and the resumption of growth. As with normal 3T3 cells, if the growth rate of BP3T3 cells is limited by a suboptimal concentration of serum, the growth rate of the cells is increased by the addition of FGF. Also, BP3T3 cells show density-dependent regulation of growth, if the medium contains a low concentration of serum. BP3T3 cells, therefore, have the behavior of \"transformed\" cells when cultured in medium with 10% serum, but behave as \"normal\" cells in medium with low serum. In comparison with normal 3T3 cells, the difference in growth behavior of BP3T3 cells appears to be due to a substantial decrease in the cells' requirement for a serum growth factor of the FGF type. Exploration of possible causes of this substantial decrease indicates that the primary cause is a lower rate of depletion of the serum growth factor from the culture medium by BP3T3 cells. The decrease in rate of depletion is sufficient to account for the uncontrolled growth of BP3T3 cells in medium with 10% serum. It is suggested that a decreased rate of depletion of a growth factor may contribute to tumorigenicity of cells in vivo."}
{"id": "PMID:184468", "title": "Loss of mouse chromosomes in somatic cell hybrids between HT-1080 human fibrosarcoma cells and mouse peritioneal macrophages.", "content": "Somatic cell hybrids between mouse peritioneal macrophages and HT-1080 human fibrosarcoma cells lose mouse chromosomes and retain the entire complement of human chromosomes. In contrast, somatic cell hybrids between cells derived from two different mouse continuous cell lines and HT-1080 human cells were found to lose human chromosomes preferentially. Loss of mouse chromosomes is not a general property of hybrids between mouse macrophages and transformed human cells; the hybridization of mouse macrophages with cells derived from five different human fibroblast lines transformed by simian virus 40 resulted in the production of hybrid clones that preferentially lost human chromosomes.", "contents": "Loss of mouse chromosomes in somatic cell hybrids between HT-1080 human fibrosarcoma cells and mouse peritioneal macrophages. Somatic cell hybrids between mouse peritioneal macrophages and HT-1080 human fibrosarcoma cells lose mouse chromosomes and retain the entire complement of human chromosomes. In contrast, somatic cell hybrids between cells derived from two different mouse continuous cell lines and HT-1080 human cells were found to lose human chromosomes preferentially. Loss of mouse chromosomes is not a general property of hybrids between mouse macrophages and transformed human cells; the hybridization of mouse macrophages with cells derived from five different human fibroblast lines transformed by simian virus 40 resulted in the production of hybrid clones that preferentially lost human chromosomes."}
{"id": "PMID:184469", "title": "Neurophysiological defects in temperature-sensitive paralytic mutants of Drosophila melanogaster.", "content": "A new temperature-sensitive paralytic mutant of Drosophila, comatose, is compared behaviorally and physiologically with the previously known types, para and shi. All three have different properties with respect to kinetics of paralysis at high temperature and recovery from paralysis; com is hypersensitive to paralysis by cooling. Neurophysiological experimeents indicate different mechanisms for paralysis in each of the mutants.", "contents": "Neurophysiological defects in temperature-sensitive paralytic mutants of Drosophila melanogaster. A new temperature-sensitive paralytic mutant of Drosophila, comatose, is compared behaviorally and physiologically with the previously known types, para and shi. All three have different properties with respect to kinetics of paralysis at high temperature and recovery from paralysis; com is hypersensitive to paralysis by cooling. Neurophysiological experimeents indicate different mechanisms for paralysis in each of the mutants."}
{"id": "PMID:184470", "title": "A fetal protein in chromatin of Novikoff hepatoma and Walker 256 carcinosarcoma tumors that is absent from normal and regenerating rat liver.", "content": "Antibodies to chromatin proteins of Novikoff hepatoma cells formed precipitin bands in the double-diffusion immunoprecipitation assay with chromatin proteins of Novikoff hepatoma, Walker 256 carcinosarcoma, and 18-day fetal rat liver. The antigen used for preparation of antiserum was the chromatin proteins initially extracted with 3 M NaCl-7 M urea and soluble after dialysis to 0.14 M NaCl-0.35 M urea. The chromatin proteins used for analytical studies were extracted with 0.6 M NaCl containing 0.01 M Tris-HCl (pH 8) and 100 muM phenylmethylsulfonyl fluoride. Corresponding chromatin proteins of normal and 18-hr regenerating rat liver, heart, and kidney did not form precipitin bands. The antigen was purified from the chrmatin of Novikoff hepatoma cells by exclusion chromatography on Sephadex G-150 and preparative nondenaturing polyacrylamide gel electrophoresis. Its migration on denaturing sodium dodecyl sulfate-polyacrylamide gels corresponded to a molecular weight of 26,000. Amino acid analysis showed that the ratio of acidic to basic amino acids was 1.4 to 1.0. Evidence for its homogeneity included its migration as a single protein spot on two-dimensional polyacrylamide gel electrophoresis and its single lysine amino-terminal amino acid. This protein is a glycoprotein, as shown by the presence of 15 moles of galactosamine per mole of antigen. These studies demonstrate the presence of a fetal glycoprotein in the chromatin of two tumors that may have an important role in determining their gene products.", "contents": "A fetal protein in chromatin of Novikoff hepatoma and Walker 256 carcinosarcoma tumors that is absent from normal and regenerating rat liver. Antibodies to chromatin proteins of Novikoff hepatoma cells formed precipitin bands in the double-diffusion immunoprecipitation assay with chromatin proteins of Novikoff hepatoma, Walker 256 carcinosarcoma, and 18-day fetal rat liver. The antigen used for preparation of antiserum was the chromatin proteins initially extracted with 3 M NaCl-7 M urea and soluble after dialysis to 0.14 M NaCl-0.35 M urea. The chromatin proteins used for analytical studies were extracted with 0.6 M NaCl containing 0.01 M Tris-HCl (pH 8) and 100 muM phenylmethylsulfonyl fluoride. Corresponding chromatin proteins of normal and 18-hr regenerating rat liver, heart, and kidney did not form precipitin bands. The antigen was purified from the chrmatin of Novikoff hepatoma cells by exclusion chromatography on Sephadex G-150 and preparative nondenaturing polyacrylamide gel electrophoresis. Its migration on denaturing sodium dodecyl sulfate-polyacrylamide gels corresponded to a molecular weight of 26,000. Amino acid analysis showed that the ratio of acidic to basic amino acids was 1.4 to 1.0. Evidence for its homogeneity included its migration as a single protein spot on two-dimensional polyacrylamide gel electrophoresis and its single lysine amino-terminal amino acid. This protein is a glycoprotein, as shown by the presence of 15 moles of galactosamine per mole of antigen. These studies demonstrate the presence of a fetal glycoprotein in the chromatin of two tumors that may have an important role in determining their gene products."}
{"id": "PMID:184471", "title": "Effect of 3':5'-cyclic GMP derivatives on the formation of Caulobacter surface structures.", "content": "Exogenous derivatives of 3':5'-cyclic GMP, 8-bromo- and N2,O2'-dibutyryl cyclic GMP, coordinately repress surface structure differentiation in Caulobacter crescentus. Growth in the presence of cyclic GMP derivatives resulted in the loss of flagella and pili formation and concomitant resistance to both DNA phage phiCbK and RNA phage phiCb5 infection without affecting growth rate, stalk formation, and equatorial cell division. The effect of cyclic GMP derivatives was shown to be the repression of synthesis of specific structural proteins. This effect could be reversed by exogenous N6,O2'-dibutyryl 3':5'-cyclic AMP, and mutants resistant to repression by cyclic GMP derivatives exhibited a pleiotropic phenotype affecting a cyclic AMP-mediated event.", "contents": "Effect of 3':5'-cyclic GMP derivatives on the formation of Caulobacter surface structures. Exogenous derivatives of 3':5'-cyclic GMP, 8-bromo- and N2,O2'-dibutyryl cyclic GMP, coordinately repress surface structure differentiation in Caulobacter crescentus. Growth in the presence of cyclic GMP derivatives resulted in the loss of flagella and pili formation and concomitant resistance to both DNA phage phiCbK and RNA phage phiCb5 infection without affecting growth rate, stalk formation, and equatorial cell division. The effect of cyclic GMP derivatives was shown to be the repression of synthesis of specific structural proteins. This effect could be reversed by exogenous N6,O2'-dibutyryl 3':5'-cyclic AMP, and mutants resistant to repression by cyclic GMP derivatives exhibited a pleiotropic phenotype affecting a cyclic AMP-mediated event."}
{"id": "PMID:184472", "title": "Effect of human nasal secretions on the antiviral activity of human fibroblast and leukocyte interferon.", "content": "Many normal human nasal secretions contain an inhibitor of human fibroblast IF. This inhibitor had no effect on human leukocyte IF. The amount of inhibition of fibroblast IF increased with increasing quantities of nasal secretions. Also, the inhibition could be overcome with increasing concentrations of IF.", "contents": "Effect of human nasal secretions on the antiviral activity of human fibroblast and leukocyte interferon. Many normal human nasal secretions contain an inhibitor of human fibroblast IF. This inhibitor had no effect on human leukocyte IF. The amount of inhibition of fibroblast IF increased with increasing quantities of nasal secretions. Also, the inhibition could be overcome with increasing concentrations of IF."}
{"id": "PMID:184473", "title": "Lutropin receptors from male and female tissues: different responses to a lutropin receptor binding inhibitor.", "content": "An inhibitor for lutropin receptor site binding (LH-RBI), which strongly inhibited the binding of 125I-labeled ovine lutropin ([125I]oLH) to ovarian LH receptors, did not inhibit the [125I]oLH binding to testicular LH receptors. Preincubation of the LH-RBI with [125I]oLH did not affect the binding of preincubated ]125I]oLH to ovarian LH receptors. No inhibition of [125I]oLH binding to testicular LH receptors was observed even uhen the concentration of LH-RBI was significantly increased or when the testicular LH receptors uere first incubated with LH-RBI prior to the addition of [125I]oLH and a second incubation. Scatchard analysis revealed that the dissociation constant of [125I]oLH binding was essentially the same in the presence or absence of LH-RBI. The results suggest that: (i) the lutropin receptor of ovaries, but not of testes, has a specific LH-RBI binding site in addition to the lutropin binding site, and (ii) the binding of the LH-RBI produces an \"allosteric\" type of inhibition to the binding of lutropin at the lutropin binding site.", "contents": "Lutropin receptors from male and female tissues: different responses to a lutropin receptor binding inhibitor. An inhibitor for lutropin receptor site binding (LH-RBI), which strongly inhibited the binding of 125I-labeled ovine lutropin ([125I]oLH) to ovarian LH receptors, did not inhibit the [125I]oLH binding to testicular LH receptors. Preincubation of the LH-RBI with [125I]oLH did not affect the binding of preincubated ]125I]oLH to ovarian LH receptors. No inhibition of [125I]oLH binding to testicular LH receptors was observed even uhen the concentration of LH-RBI was significantly increased or when the testicular LH receptors uere first incubated with LH-RBI prior to the addition of [125I]oLH and a second incubation. Scatchard analysis revealed that the dissociation constant of [125I]oLH binding was essentially the same in the presence or absence of LH-RBI. The results suggest that: (i) the lutropin receptor of ovaries, but not of testes, has a specific LH-RBI binding site in addition to the lutropin binding site, and (ii) the binding of the LH-RBI produces an \"allosteric\" type of inhibition to the binding of lutropin at the lutropin binding site."}
{"id": "PMID:184474", "title": "Role of converting enzyme in the cardiovascular and adrenal cortical responses to (des-Asp1)-angiotensin I.", "content": "(Des-Asp1)-angiotensin I, angiotensin II and III were evaluated for pressor activities in conscious nephrectomized rats and for steroidogenic actions in rat adrenal zona glomerulosa. The pressor effect of this angiotensin nonapeptide was similar to that found with mole-equivalent doses of angiotensin III (one-third as active as angiotensin II) and was significantly attenuated by pretreatment with the 0. jararaca nonapeptide converting enzyme inhibitor. Hence, (des-Asp1)-angiotensin I is a substrate for converting enzyme in vivo, and the rapid conversion indicates that an alternate pathway for the formation of angiotensin III could exist. (Des-Asp1)-angiotensin I possessed only 0.1% of the activity of angiotensin III as a steroidogenic agent in cell suspensions of rat adrenal zona glomerulosa. Angiotensin I was a weak steroidogenic agent in vitro (1%) and was not blocked by an inhibitor of converting enzyme. Adrenal cells dispersed from the outer zone of the cortex would appear to be devoid of significant converting enzyme activity.", "contents": "Role of converting enzyme in the cardiovascular and adrenal cortical responses to (des-Asp1)-angiotensin I. (Des-Asp1)-angiotensin I, angiotensin II and III were evaluated for pressor activities in conscious nephrectomized rats and for steroidogenic actions in rat adrenal zona glomerulosa. The pressor effect of this angiotensin nonapeptide was similar to that found with mole-equivalent doses of angiotensin III (one-third as active as angiotensin II) and was significantly attenuated by pretreatment with the 0. jararaca nonapeptide converting enzyme inhibitor. Hence, (des-Asp1)-angiotensin I is a substrate for converting enzyme in vivo, and the rapid conversion indicates that an alternate pathway for the formation of angiotensin III could exist. (Des-Asp1)-angiotensin I possessed only 0.1% of the activity of angiotensin III as a steroidogenic agent in cell suspensions of rat adrenal zona glomerulosa. Angiotensin I was a weak steroidogenic agent in vitro (1%) and was not blocked by an inhibitor of converting enzyme. Adrenal cells dispersed from the outer zone of the cortex would appear to be devoid of significant converting enzyme activity."}
{"id": "PMID:184475", "title": "Characterization of extracellular particles released from continuous cell cultures derived from human leukemia.", "content": "Extracellular particles, with a density of 1.18-1.22 g/cm3 in sucrose, were detected in the culture medium of a continuous cell line (JIII) derived from a patient with monocytic leukemia. These particles contained RNA, DNA, and a DNA polymerase. They synthesized DNA with endogenous templates and primers and also used exogenous DNA but not poly(rC) oligo(dG) as a template. Pretreatment with Nonidet P-40 stimulated DNA polymerase activity while treatment with ribonuclease partially inhibited the enzyme activity. Fluorescent antibodies made to the particles stained both JIII and Z-597 cells derived from human leukemias but not other types of human or nonhuman cultured cells tested. The particles do not appear to be oncornaviruses but may be a particulate antigen associated with malignant cells of hemopoietic and lymphoid origin.", "contents": "Characterization of extracellular particles released from continuous cell cultures derived from human leukemia. Extracellular particles, with a density of 1.18-1.22 g/cm3 in sucrose, were detected in the culture medium of a continuous cell line (JIII) derived from a patient with monocytic leukemia. These particles contained RNA, DNA, and a DNA polymerase. They synthesized DNA with endogenous templates and primers and also used exogenous DNA but not poly(rC) oligo(dG) as a template. Pretreatment with Nonidet P-40 stimulated DNA polymerase activity while treatment with ribonuclease partially inhibited the enzyme activity. Fluorescent antibodies made to the particles stained both JIII and Z-597 cells derived from human leukemias but not other types of human or nonhuman cultured cells tested. The particles do not appear to be oncornaviruses but may be a particulate antigen associated with malignant cells of hemopoietic and lymphoid origin."}
{"id": "PMID:184476", "title": "Occurrence in human bone marrows of an antigen released from continuous cell cultures derived from human leukemia.", "content": "Fluorescent antibodies prepared against extracellular particles from a continuous culture of cells derived from a monocytic leukemia stained JIII cells but not cells infected with Rauscher leukemia virus or simian sarcoma virus. These antibodies reacted with 38% of bone marrow preparations from patients with lymphoma, 26% of preparations from patients with nonmalignant blood disorders and 6% of preparations from patients with leukemia. Bone marrow films from patients with lymphoma over the age of 50 stained less frequently than those from patients under 50. These particles released from JIII cells are not antigenically related to two of the commonly studied oncornaviruses, but may be indicative of the etiology or disease process of lymphoma in young patients.", "contents": "Occurrence in human bone marrows of an antigen released from continuous cell cultures derived from human leukemia. Fluorescent antibodies prepared against extracellular particles from a continuous culture of cells derived from a monocytic leukemia stained JIII cells but not cells infected with Rauscher leukemia virus or simian sarcoma virus. These antibodies reacted with 38% of bone marrow preparations from patients with lymphoma, 26% of preparations from patients with nonmalignant blood disorders and 6% of preparations from patients with leukemia. Bone marrow films from patients with lymphoma over the age of 50 stained less frequently than those from patients under 50. These particles released from JIII cells are not antigenically related to two of the commonly studied oncornaviruses, but may be indicative of the etiology or disease process of lymphoma in young patients."}
{"id": "PMID:184477", "title": "Acyl group composition of membrane phospholipids in mammary tissues and carcinoma induced by dimethylbenz(a)anthracene.", "content": "Phospholipids and their acyl group composition in mammary adenocarcinomas and mammary tissue of the same tumor-bearing animals were investigated. Breast adenocarcinoma induced by dimethybenz(a)anthracene exhibited a phospholipid pattern which was different from that of the mammary tissue. Tumor phospholipids had higher proportions of diacyl-GPI, diacyl-GPE, and alkenylacyl-GPE and a lower proportion of diacyl-GPC than the controls. The acyl groups of most phospholipids in tumors showed a marked increase in the proportion of 18:1 and a decrease in the proportion of 18:2. The fatty acid composition of plasmalogen and triglyceride, however, remained unchanged. In spite of the decrease in the proportion of 18:2, there was no apparent difference in the proportion of 20:4 in most of the phosphoglycerides; however, a significant decrease in this fatty acid was noted in diacyl-GPI. Results of this study demonstrated that the membrane phospholipids of mammary adenocarcinoma were altered in respect to acyl group composition. Changes in physical properties of the cell membrane, in turn, could lead to abnormal manifestation of membrane regulated events in tumor cells.", "contents": "Acyl group composition of membrane phospholipids in mammary tissues and carcinoma induced by dimethylbenz(a)anthracene. Phospholipids and their acyl group composition in mammary adenocarcinomas and mammary tissue of the same tumor-bearing animals were investigated. Breast adenocarcinoma induced by dimethybenz(a)anthracene exhibited a phospholipid pattern which was different from that of the mammary tissue. Tumor phospholipids had higher proportions of diacyl-GPI, diacyl-GPE, and alkenylacyl-GPE and a lower proportion of diacyl-GPC than the controls. The acyl groups of most phospholipids in tumors showed a marked increase in the proportion of 18:1 and a decrease in the proportion of 18:2. The fatty acid composition of plasmalogen and triglyceride, however, remained unchanged. In spite of the decrease in the proportion of 18:2, there was no apparent difference in the proportion of 20:4 in most of the phosphoglycerides; however, a significant decrease in this fatty acid was noted in diacyl-GPI. Results of this study demonstrated that the membrane phospholipids of mammary adenocarcinoma were altered in respect to acyl group composition. Changes in physical properties of the cell membrane, in turn, could lead to abnormal manifestation of membrane regulated events in tumor cells."}
{"id": "PMID:184480", "title": "[The influence of sulpirid on sleep. Results of polygraphic night sleep recordings (author's transl)].", "content": "Short and long term effects of sulpirid on the sleep EEG in humans were investigated in 8 patients aged 20-68 years (average 40.4) suffering from autonomic instability. In each patient seven polygraphic night sleep recording were performed. After an adaption night and two nights without medication each subject got 200-400 mg sulpirid i.m. for two days and then 300-600 mg orally for a three-week period. In both groups the short-term application of sulpirid caused a reduction of waking periods and a slight decrease of stage 3, while stage 2 was increased. In psychotic patients the long-term orally administered substance was followed by an increase of deep synchronous sleep (stage 4). As this alteration of sleep couldn't be revealed in the control group, we consider this finding as a result of the improvement of psychosis. In the patient group the amount of REM sleep was augmented during the short-term application as well as during the long-term application, where, as in the control group the amount of REM sleep decreased when sulpirid was given orally for three weeks. This result is discussed in comparison with the properties of the tricyclic antidepressant drugs and monoamine oxidase inhibitors and the clinical effects of sulpiride.", "contents": "[The influence of sulpirid on sleep. Results of polygraphic night sleep recordings (author's transl)]. Short and long term effects of sulpirid on the sleep EEG in humans were investigated in 8 patients aged 20-68 years (average 40.4) suffering from autonomic instability. In each patient seven polygraphic night sleep recording were performed. After an adaption night and two nights without medication each subject got 200-400 mg sulpirid i.m. for two days and then 300-600 mg orally for a three-week period. In both groups the short-term application of sulpirid caused a reduction of waking periods and a slight decrease of stage 3, while stage 2 was increased. In psychotic patients the long-term orally administered substance was followed by an increase of deep synchronous sleep (stage 4). As this alteration of sleep couldn't be revealed in the control group, we consider this finding as a result of the improvement of psychosis. In the patient group the amount of REM sleep was augmented during the short-term application as well as during the long-term application, where, as in the control group the amount of REM sleep decreased when sulpirid was given orally for three weeks. This result is discussed in comparison with the properties of the tricyclic antidepressant drugs and monoamine oxidase inhibitors and the clinical effects of sulpiride."}
{"id": "PMID:184481", "title": "Experimental considerations in biological ESR studies. I. Identity and origin of the 'tissue lipid signal': a copper-dithiocarbamate complex.", "content": "The complex ESR signal previously observed in fatty tissues has been identified. It is a copper low-molecular-weight sulphur compound complex similar to copper-dithiocarbamate. The usual source of this signal is contact of copper-containing tissue with surgeon's gloves. This result emphasizes the care that must be taken in obtaining and interpreting ESR spectra of tissues. The formation of this complex by intentionally adding dithiocarbamate to tissue can be used as a very simple and sensitive analytical method for tissue copper. Copper levels of less than 0-1 ppm can be detected by this method. This is an order of magnitude more sensitive than determinations by atomic absorption.", "contents": "Experimental considerations in biological ESR studies. I. Identity and origin of the 'tissue lipid signal': a copper-dithiocarbamate complex. The complex ESR signal previously observed in fatty tissues has been identified. It is a copper low-molecular-weight sulphur compound complex similar to copper-dithiocarbamate. The usual source of this signal is contact of copper-containing tissue with surgeon's gloves. This result emphasizes the care that must be taken in obtaining and interpreting ESR spectra of tissues. The formation of this complex by intentionally adding dithiocarbamate to tissue can be used as a very simple and sensitive analytical method for tissue copper. Copper levels of less than 0-1 ppm can be detected by this method. This is an order of magnitude more sensitive than determinations by atomic absorption."}
{"id": "PMID:184483", "title": "The effect of diethyldithiocarbamate on passive avoidance learning by chicks (Gallus domesticus).", "content": "Diethyldithiocarbamate (DDC), a competitive inhibitor of dopamine-B-hydroxylase, produced a dosage-related depletion of neural NE and impairment of passive avoidance learning in young chicks. Retention was not impaired, however, as shown by normal relearning of the task a day later, when the drug was no longer active. Perhaps, neural NE depletion impairs ability to inhibit responding and, thus, impairs passive or inhibitory avoidance learning indirectly. Alternatively, NE depletion may slow down learning by interfering with consolidation, but if the task is well learned, it is remembered.", "contents": "The effect of diethyldithiocarbamate on passive avoidance learning by chicks (Gallus domesticus). Diethyldithiocarbamate (DDC), a competitive inhibitor of dopamine-B-hydroxylase, produced a dosage-related depletion of neural NE and impairment of passive avoidance learning in young chicks. Retention was not impaired, however, as shown by normal relearning of the task a day later, when the drug was no longer active. Perhaps, neural NE depletion impairs ability to inhibit responding and, thus, impairs passive or inhibitory avoidance learning indirectly. Alternatively, NE depletion may slow down learning by interfering with consolidation, but if the task is well learned, it is remembered."}
{"id": "PMID:184488", "title": "[Mineral metabolism of the growing bone and its disturbances--methods of radiological examinations (author's transl)].", "content": "New possible interactions of vitamin D and its derivates are discussed with reference to metabolism of calcium and phosphorous and its effects on the skeletal system. The degree of osteoporosis and osteomalacia determined only by means of roentgenology depends on subjective factors. A survey is presented about objective determination which includes skeletal mineral content by radiology and nuclear medicine examination. Following a survey of our own investigative methods and results the follow-ups in various forms of vitamin D refractory rickets are reported.", "contents": "[Mineral metabolism of the growing bone and its disturbances--methods of radiological examinations (author's transl)]. New possible interactions of vitamin D and its derivates are discussed with reference to metabolism of calcium and phosphorous and its effects on the skeletal system. The degree of osteoporosis and osteomalacia determined only by means of roentgenology depends on subjective factors. A survey is presented about objective determination which includes skeletal mineral content by radiology and nuclear medicine examination. Following a survey of our own investigative methods and results the follow-ups in various forms of vitamin D refractory rickets are reported."}
{"id": "PMID:184489", "title": "[Methods of radiological bone age assessment (author's transl)].", "content": "An assessment of the bone age can be made in different manners. Numerical methods calculating the number of existing ossification centers are to inaccurate. The use of \"age-of-appearance\" tables gives a more accurate evaluation. In both methods, however, x-ray films of several body parts must be made. Therefore, they are complicated and lead to a higher patient radiation exposure. Methods using hand and wrist as a representative area of the whole skeleton are of greater value for routine bone-age assessments. There is a wide-spread use of the Greulich-Pyle atlas. The atlas-method is fully sufficient in the great majority of cases when certain rules are considered. A more detailed information can be achieved by using the so-called \"bone-by-bone\" evaluation. A score system was introduced by Tanner and Whitehouse which should be used to a greater extent than is done up to now. Metrical methods give no real information about the bone age but additional informations which can be helpful in following examinations with short intervals.", "contents": "[Methods of radiological bone age assessment (author's transl)]. An assessment of the bone age can be made in different manners. Numerical methods calculating the number of existing ossification centers are to inaccurate. The use of \"age-of-appearance\" tables gives a more accurate evaluation. In both methods, however, x-ray films of several body parts must be made. Therefore, they are complicated and lead to a higher patient radiation exposure. Methods using hand and wrist as a representative area of the whole skeleton are of greater value for routine bone-age assessments. There is a wide-spread use of the Greulich-Pyle atlas. The atlas-method is fully sufficient in the great majority of cases when certain rules are considered. A more detailed information can be achieved by using the so-called \"bone-by-bone\" evaluation. A score system was introduced by Tanner and Whitehouse which should be used to a greater extent than is done up to now. Metrical methods give no real information about the bone age but additional informations which can be helpful in following examinations with short intervals."}
{"id": "PMID:184490", "title": "[Significance of bone age estimation to the clinic (author's transl)].", "content": "1. Typical alterations of bone maturation may be observed in many growth disturbances, e.g. consitutional delay of growth and development, early normal puberty and precocious puberty. They may be helpful for diagnosis and differential diagnosis. 2. Within certain limits it is possible to predict the definite adult stature of a child from his measured height and bone age. The prognosis frequently results in therapeutical consequences. 3. In order to correctly perform and evaluate hormonal treatment in endocrinopathies, regular controls of bone age are of utmost importance during childhood.", "contents": "[Significance of bone age estimation to the clinic (author's transl)]. 1. Typical alterations of bone maturation may be observed in many growth disturbances, e.g. consitutional delay of growth and development, early normal puberty and precocious puberty. They may be helpful for diagnosis and differential diagnosis. 2. Within certain limits it is possible to predict the definite adult stature of a child from his measured height and bone age. The prognosis frequently results in therapeutical consequences. 3. In order to correctly perform and evaluate hormonal treatment in endocrinopathies, regular controls of bone age are of utmost importance during childhood."}
{"id": "PMID:184494", "title": "Prostaglandins and inflammation: enhancement of monocyte chemotactic responsiveness by prostaglandin E2.", "content": "The effects of prostaglandins on human monocyte chemotaxis were studied in vitro. None of the prostaglandins tested, including members of the A, B, E or F series, were chemotactic for monocytes. Prostaglandin E2 however, enhanced the chemotactic responsiveness of monocytes to complement - activated human serum by almost 200%. The enhancement of chemotaxis was not directly related to the ability of PGE2 to raise intracellular cyclic AMP levels. These studies support a role for prostaglandins as modulators of the inflammatory response.", "contents": "Prostaglandins and inflammation: enhancement of monocyte chemotactic responsiveness by prostaglandin E2. The effects of prostaglandins on human monocyte chemotaxis were studied in vitro. None of the prostaglandins tested, including members of the A, B, E or F series, were chemotactic for monocytes. Prostaglandin E2 however, enhanced the chemotactic responsiveness of monocytes to complement - activated human serum by almost 200%. The enhancement of chemotaxis was not directly related to the ability of PGE2 to raise intracellular cyclic AMP levels. These studies support a role for prostaglandins as modulators of the inflammatory response."}
{"id": "PMID:184495", "title": "Effects of prostaglandins and other drugs on the cyclic AMP content of cultured bone cells.", "content": "Prostaglandins of the E-series (PGE1 and PGE2) may be involved in disease-related, localized loss of bone. E-prostaglandins increase the cyclic AMP content of many cells; and, to determine if their effects on bone are mediated by cyclic AMP, we examined the effects of E-prostaglandins and of other agents on the cyclic AMP content of cultured bone cells. PGE2 produced a rapid, marked and dose-related increase in the cyclic AMP content of confluent monolayers of bone cells isolated from newborn rat calvaria. At 2.8 X 10(-6) M, PGE1 and PGE2 had approximately the same effect, while the effect of PGF2alpha was much less pronounced. In the presence of theophylline, PGE2 had a more marked effect than parathyroid hormone (PTH) and the combination of PGE2 and PTH had a synergistic effect. The divalent, cationic, ionophore, A23187, produced an increase in cellular cyclic AMP and had an additive effect in combination with PGE2. Synthetic salmon calcitonin (CT), which inhibits the bone resorptive effect of PGE2, increased cellular cyclic AMP and had an additive effect in combination with PGE2. A prostaglandin antagonist, SC-19220, partially inhibited the resorptive effect of PGE2 and reduced its effect on cellular cyclic AMP. The calcium antagonist, D600, inhibited the bone resorptive effects of PGE2 but had no effect on increased cellular cyclic AMP produced by PGE2. The marked effect of PGE2 on bone cell cyclic AMP suggests that this action is involved in the mechanism of PGE2-related bone loss. The fact that agents with different effects on PGE2-induced increases in cellular cyclic AMP can inhibit its resorptive actions, suggests that PGE2-induced changes in cyclic AMP may be related less to its resorptive actions than to its inhibitory effect on bone formation.", "contents": "Effects of prostaglandins and other drugs on the cyclic AMP content of cultured bone cells. Prostaglandins of the E-series (PGE1 and PGE2) may be involved in disease-related, localized loss of bone. E-prostaglandins increase the cyclic AMP content of many cells; and, to determine if their effects on bone are mediated by cyclic AMP, we examined the effects of E-prostaglandins and of other agents on the cyclic AMP content of cultured bone cells. PGE2 produced a rapid, marked and dose-related increase in the cyclic AMP content of confluent monolayers of bone cells isolated from newborn rat calvaria. At 2.8 X 10(-6) M, PGE1 and PGE2 had approximately the same effect, while the effect of PGF2alpha was much less pronounced. In the presence of theophylline, PGE2 had a more marked effect than parathyroid hormone (PTH) and the combination of PGE2 and PTH had a synergistic effect. The divalent, cationic, ionophore, A23187, produced an increase in cellular cyclic AMP and had an additive effect in combination with PGE2. Synthetic salmon calcitonin (CT), which inhibits the bone resorptive effect of PGE2, increased cellular cyclic AMP and had an additive effect in combination with PGE2. A prostaglandin antagonist, SC-19220, partially inhibited the resorptive effect of PGE2 and reduced its effect on cellular cyclic AMP. The calcium antagonist, D600, inhibited the bone resorptive effects of PGE2 but had no effect on increased cellular cyclic AMP produced by PGE2. The marked effect of PGE2 on bone cell cyclic AMP suggests that this action is involved in the mechanism of PGE2-related bone loss. The fact that agents with different effects on PGE2-induced increases in cellular cyclic AMP can inhibit its resorptive actions, suggests that PGE2-induced changes in cyclic AMP may be related less to its resorptive actions than to its inhibitory effect on bone formation."}
{"id": "PMID:184506", "title": "Attempts to produce Theileria parva-infected mouse cells using cell fusion techniques.", "content": "Ehrlich ascites tumour (EAT) cells were fused with Theileria parva-infected bovine lymphoid (C2) cells using inactivated Sendai virus. A variety of techniques were employed to try and increase fusion percentage and harvest of heterokaryons. There was no evidence that pre-exposure of C2 cells to Sendai virus or phytohaemagglutinin improved fusion percentage, but the percentage was higher when 10(8) C2 cells were fused with 10(7) EAT cells, as compared with a ratio of 10(7) C2: 10(6) EAT. An increased yield of multinucleate cells was obtained using a calf serum gradient to separate cells of different sizes. An attempt to fuse EAT cells with free macroschizonts was not sucessful. When cells were grown in hypoxanthine/aminopterin/thymidine medium (HAT), T parva appeared to be selectively killed by the aminopterin present; this finding would seem to militate against the use of a HAT selection system to clone parasitised hybrids. C2 cells could be selected out by passage of mixed cultures through mice, but no evidence of parasitosis was detected in EAT cells which became established.", "contents": "Attempts to produce Theileria parva-infected mouse cells using cell fusion techniques. Ehrlich ascites tumour (EAT) cells were fused with Theileria parva-infected bovine lymphoid (C2) cells using inactivated Sendai virus. A variety of techniques were employed to try and increase fusion percentage and harvest of heterokaryons. There was no evidence that pre-exposure of C2 cells to Sendai virus or phytohaemagglutinin improved fusion percentage, but the percentage was higher when 10(8) C2 cells were fused with 10(7) EAT cells, as compared with a ratio of 10(7) C2: 10(6) EAT. An increased yield of multinucleate cells was obtained using a calf serum gradient to separate cells of different sizes. An attempt to fuse EAT cells with free macroschizonts was not sucessful. When cells were grown in hypoxanthine/aminopterin/thymidine medium (HAT), T parva appeared to be selectively killed by the aminopterin present; this finding would seem to militate against the use of a HAT selection system to clone parasitised hybrids. C2 cells could be selected out by passage of mixed cultures through mice, but no evidence of parasitosis was detected in EAT cells which became established."}
{"id": "PMID:184508", "title": "Pulmonary reflexes and breathing pattern during sleep in the opossum.", "content": "Paradoxical sleep (PS) in the opossum (Didelphis virginiana) and other mammals is typically accompanied by irregular breathing, while even breathing is usually found during slow wave sleep (SWS). During PS certain brainstem reflexes are depressed, and it is possible that similar depression of pulmonary reflexes could contribute to the observed ventilatory uneveness. To test this possibility, we assessed pulmonary reflexes in the opossum during SWS and during PS when breathing was irregular. Prolongation of expiratory duration with airway occlusion at end inspiration and prolongation of inspiratory duration with airway occlusion at end expiration are both associated with pulmonary reflexes activated by lung inflation. These responses were obtained during PS, and the results suggested that the reflex effects, could be as prominent during PS as during SWS. Pulmonary deflation, producted by raising pressure around the thorax, increased breathing rate during both PS and SWS and generally increased the regularity of respiration during PS. Results of this study do not support the idea that irregular breathing during PS is associated wtih maintained depression of pulmonary reflexes.", "contents": "Pulmonary reflexes and breathing pattern during sleep in the opossum. Paradoxical sleep (PS) in the opossum (Didelphis virginiana) and other mammals is typically accompanied by irregular breathing, while even breathing is usually found during slow wave sleep (SWS). During PS certain brainstem reflexes are depressed, and it is possible that similar depression of pulmonary reflexes could contribute to the observed ventilatory uneveness. To test this possibility, we assessed pulmonary reflexes in the opossum during SWS and during PS when breathing was irregular. Prolongation of expiratory duration with airway occlusion at end inspiration and prolongation of inspiratory duration with airway occlusion at end expiration are both associated with pulmonary reflexes activated by lung inflation. These responses were obtained during PS, and the results suggested that the reflex effects, could be as prominent during PS as during SWS. Pulmonary deflation, producted by raising pressure around the thorax, increased breathing rate during both PS and SWS and generally increased the regularity of respiration during PS. Results of this study do not support the idea that irregular breathing during PS is associated wtih maintained depression of pulmonary reflexes."}
{"id": "PMID:184510", "title": "[Hansen's neuritis in the form of pseudysyringomyelia. Clinical, diagnostic and therapeutic consideration a propos of 3 cases].", "content": "Three cases of neuropathic leprosy (one Moroccan, two non-colonial immigrants) enable attention to be drawn to two aspects of theproblem of Hansen's neuritis: 1) such cases should no longer be considered exceptional, infection occuring in countries where leprosy is endemic but the disease developing years later in any country; 2) among the various neurological aspects of neuritis due to Hansen's bacillus, great stress is laid on sensory disorders of the syringomyelic type, with thermalgesic dissociation; although these symptoms have been considered typical (our three cases are an illustration of this), they seem to occur fairly rarely and are the cause of difficulties in diagnosis as it is the last thing one would think of. Treatment of these neural forms is not encouraging, in spite of a therapeutic arsenal which in theory is considered effective.", "contents": "[Hansen's neuritis in the form of pseudysyringomyelia. Clinical, diagnostic and therapeutic consideration a propos of 3 cases]. Three cases of neuropathic leprosy (one Moroccan, two non-colonial immigrants) enable attention to be drawn to two aspects of theproblem of Hansen's neuritis: 1) such cases should no longer be considered exceptional, infection occuring in countries where leprosy is endemic but the disease developing years later in any country; 2) among the various neurological aspects of neuritis due to Hansen's bacillus, great stress is laid on sensory disorders of the syringomyelic type, with thermalgesic dissociation; although these symptoms have been considered typical (our three cases are an illustration of this), they seem to occur fairly rarely and are the cause of difficulties in diagnosis as it is the last thing one would think of. Treatment of these neural forms is not encouraging, in spite of a therapeutic arsenal which in theory is considered effective."}
{"id": "PMID:184511", "title": "[Mixed neuropathies in rheumatoid arthritis. Motor and sensory nerve conduction velocities].", "content": "Nerve conduction studies and analysis of the sensory action potential (110 nerves investigated) demons treated abnormalities in 15 to 20 patients with rheumatoid arthritis. It is concluded that moderate, often subclinical peripheral neuropathy is a common complication in rheumatoid arthritis.", "contents": "[Mixed neuropathies in rheumatoid arthritis. Motor and sensory nerve conduction velocities]. Nerve conduction studies and analysis of the sensory action potential (110 nerves investigated) demons treated abnormalities in 15 to 20 patients with rheumatoid arthritis. It is concluded that moderate, often subclinical peripheral neuropathy is a common complication in rheumatoid arthritis."}
{"id": "PMID:184512", "title": "[Sleep disorders in Steele-Richardson disease. Polygraphic study of 3 cases].", "content": "24 recordings of night-time sleep in three patients suffering from progressive supranuclear paralysis were carried out. There was observed: a tendency to insomnia, disappearance of spindles, an invasion of slow sleep immediately it appeared by the muscular and ocular criteria of paradoxical sleep, a considerable reduction in paradoxical sleep in the strict sense of the term, the latency of which in making its appearance was, however, maintained; progressive invasion of the paradoxical phases by slow waves. These abnormalities differ from those found in Parkinson's disease.", "contents": "[Sleep disorders in Steele-Richardson disease. Polygraphic study of 3 cases]. 24 recordings of night-time sleep in three patients suffering from progressive supranuclear paralysis were carried out. There was observed: a tendency to insomnia, disappearance of spindles, an invasion of slow sleep immediately it appeared by the muscular and ocular criteria of paradoxical sleep, a considerable reduction in paradoxical sleep in the strict sense of the term, the latency of which in making its appearance was, however, maintained; progressive invasion of the paradoxical phases by slow waves. These abnormalities differ from those found in Parkinson's disease."}
{"id": "PMID:184513", "title": "[Volitional postural dyskinesia with hypertrophic neuropathy].", "content": "Two cases of voluntary postural dyskinesia with hypertrophic neuropathy are reported. Electron-microscope studies revealed in one case a hypertrophic neuropathy with onion bulb formation, in the other axonal degeneration. The findings are compared with those of Pierre Marie-Boveri disease, of Roussy-L\u00e9vy disease and with the case of Salisachs and Lapresle (1973).", "contents": "[Volitional postural dyskinesia with hypertrophic neuropathy]. Two cases of voluntary postural dyskinesia with hypertrophic neuropathy are reported. Electron-microscope studies revealed in one case a hypertrophic neuropathy with onion bulb formation, in the other axonal degeneration. The findings are compared with those of Pierre Marie-Boveri disease, of Roussy-L\u00e9vy disease and with the case of Salisachs and Lapresle (1973)."}
{"id": "PMID:184514", "title": "[Neurological manifestations in monoclonal gammapathies. Pure neurological manifestations. Immunofluorescence study].", "content": "Analysis of 105 peripheral and central nervous system complications in 1062 monoclonal gammapathies draws attention to two types of phenomena. The possibility of pure neurological manifestations of IgM monoclonal gammapathies with macroglobulinorachia leads to discussion of their nosological position in relation to Waldenstr\u00f6m's disease, Burkitt's lymphoma and Marek's disease. It is suggested that these cases should be reclassified under the heading \"secreting neurolymphomatosis\". Immunofluorescence and electron microscopy of 10 biopsies of the peripheral nerve showed deposits of monoclonal immunoglobulin whose function in determining peripheral neuropathies is discussed. The simultaneous presence of lymphoid infiltration, amyloid deposits and the monoclonal immunoglobulin (M component) suggests that this immunoglobulin could be the link between the cellular infiltrate secreting it and amyloid infiltration which would be the visible manifestation of it.", "contents": "[Neurological manifestations in monoclonal gammapathies. Pure neurological manifestations. Immunofluorescence study]. Analysis of 105 peripheral and central nervous system complications in 1062 monoclonal gammapathies draws attention to two types of phenomena. The possibility of pure neurological manifestations of IgM monoclonal gammapathies with macroglobulinorachia leads to discussion of their nosological position in relation to Waldenstr\u00f6m's disease, Burkitt's lymphoma and Marek's disease. It is suggested that these cases should be reclassified under the heading \"secreting neurolymphomatosis\". Immunofluorescence and electron microscopy of 10 biopsies of the peripheral nerve showed deposits of monoclonal immunoglobulin whose function in determining peripheral neuropathies is discussed. The simultaneous presence of lymphoid infiltration, amyloid deposits and the monoclonal immunoglobulin (M component) suggests that this immunoglobulin could be the link between the cellular infiltrate secreting it and amyloid infiltration which would be the visible manifestation of it."}
{"id": "PMID:184515", "title": "[Clinical syndrome of convulsive cough of adenoviral etiology in a children's collective].", "content": "Bacteriological, viral and serological investigators were carried out in a community with 100 prescholar children (Kindergarden), 34 of whom presented a clinical syndrome of whooping cough, in order to establish the bacteriologic or viral etiology of the syndrome. The etiologic role of organisms of the Bordetella, B. pertussis and B. parapertussis was invalidated by the bacteriologic and serological tests. Viral and serological tests, performed to demonstrate the participation of viral agents in the causation of this clinical syndrome, established an adenoviral diagnosis in 13 (43.3%) of the 30 children. Adenovirus type 6 was isolated and there was a significant increase in the titers of antibodies to adenoviruses.", "contents": "[Clinical syndrome of convulsive cough of adenoviral etiology in a children's collective]. Bacteriological, viral and serological investigators were carried out in a community with 100 prescholar children (Kindergarden), 34 of whom presented a clinical syndrome of whooping cough, in order to establish the bacteriologic or viral etiology of the syndrome. The etiologic role of organisms of the Bordetella, B. pertussis and B. parapertussis was invalidated by the bacteriologic and serological tests. Viral and serological tests, performed to demonstrate the participation of viral agents in the causation of this clinical syndrome, established an adenoviral diagnosis in 13 (43.3%) of the 30 children. Adenovirus type 6 was isolated and there was a significant increase in the titers of antibodies to adenoviruses."}
{"id": "PMID:184520", "title": "Ultrastructural aspects of crystal-like inclusions in a case of IgA plasma cell proliferation.", "content": "A case of apparently benign plasma cell proliferation is described. Needle-like paracrystalline inclusions were observed in numerous plasma cells outside the cisternae of the rough endoplasmic reticulum. They had a dense protein core surrounded by a layer of carbohydrate. They were found only in plasma cells secreting IgA-kappa immunoglobulin, but did not react with labelled specific antisera. A small amount of paraprotein IgA-kappa was found in the serum but no Bence-Jones protein could be detected in the urine. These observations suggest that these plasma cells synthesize normal IgA immunoglobulin and accumulate abnormal protein in the form of paracrystalline inclusions.", "contents": "Ultrastructural aspects of crystal-like inclusions in a case of IgA plasma cell proliferation. A case of apparently benign plasma cell proliferation is described. Needle-like paracrystalline inclusions were observed in numerous plasma cells outside the cisternae of the rough endoplasmic reticulum. They had a dense protein core surrounded by a layer of carbohydrate. They were found only in plasma cells secreting IgA-kappa immunoglobulin, but did not react with labelled specific antisera. A small amount of paraprotein IgA-kappa was found in the serum but no Bence-Jones protein could be detected in the urine. These observations suggest that these plasma cells synthesize normal IgA immunoglobulin and accumulate abnormal protein in the form of paracrystalline inclusions."}
{"id": "PMID:184516", "title": "[Some respiratory viruses in the etiology of acute upper respiratory infections].", "content": "The viral etiology of acute respiratory diseases, determined in 107 children admitted to hospital during the 1966-1969 period, was confirmed in 36% of the cases by isolation of the viral agent and in 59% by serologic reactions. Parainfluenza viruses, especially of type 1 and 3, were encountered more often in the etiology of acute or obstructive laryngitis, and the syncytial respiratory virus in tracheobronchitis.", "contents": "[Some respiratory viruses in the etiology of acute upper respiratory infections]. The viral etiology of acute respiratory diseases, determined in 107 children admitted to hospital during the 1966-1969 period, was confirmed in 36% of the cases by isolation of the viral agent and in 59% by serologic reactions. Parainfluenza viruses, especially of type 1 and 3, were encountered more often in the etiology of acute or obstructive laryngitis, and the syncytial respiratory virus in tracheobronchitis."}
{"id": "PMID:184521", "title": "Thrombin-induced platelet prostaglandin and cyclic AMP production and a possible intrinsic modulation of platelet function.", "content": "In previous studies, we observed an increase in intracellular cyclic AMP in platelets during thrombin-induced nucleotide and calcium release. Our present work suggests that platelet prostaglandins are directly involved in this phenomenon. Washed human platelets were incubated at 37 degrees C with human thrombin for times ranging between 5 s and 5 min. The release of nucleotides and calcium in response to thrombin, determined spectrophotometrically, reached 40-60% of maximal plateau levels by 5 s, 70-80% by 10 s, and 90-100% by 15 s. The production and secretion of prostaglandin E (PGE), measured by radioimmunoassay, parelleled this rapid time course. After 10 s, however, the amount of extracellular PGE began to decrease, continuing to do so through 5 min of incubation. Intracellular cyclic AMP accumulation, determined by radioimmunoassay, lagged behind the time course of nucleotide and calcium release, and that of PGE secretion, by several seconds. This lag in cyclic AMP accumulation appeared to correlate closely with the disappearance of PGE from the supernate in the same platelet samples. In view of the inhibitory effects of cyclic AMP and PGE on platelet release and aggregation, these interrelated time course curves suggest the existence within platelets of a mechanism for the modulation of platelet activity.", "contents": "Thrombin-induced platelet prostaglandin and cyclic AMP production and a possible intrinsic modulation of platelet function. In previous studies, we observed an increase in intracellular cyclic AMP in platelets during thrombin-induced nucleotide and calcium release. Our present work suggests that platelet prostaglandins are directly involved in this phenomenon. Washed human platelets were incubated at 37 degrees C with human thrombin for times ranging between 5 s and 5 min. The release of nucleotides and calcium in response to thrombin, determined spectrophotometrically, reached 40-60% of maximal plateau levels by 5 s, 70-80% by 10 s, and 90-100% by 15 s. The production and secretion of prostaglandin E (PGE), measured by radioimmunoassay, parelleled this rapid time course. After 10 s, however, the amount of extracellular PGE began to decrease, continuing to do so through 5 min of incubation. Intracellular cyclic AMP accumulation, determined by radioimmunoassay, lagged behind the time course of nucleotide and calcium release, and that of PGE secretion, by several seconds. This lag in cyclic AMP accumulation appeared to correlate closely with the disappearance of PGE from the supernate in the same platelet samples. In view of the inhibitory effects of cyclic AMP and PGE on platelet release and aggregation, these interrelated time course curves suggest the existence within platelets of a mechanism for the modulation of platelet activity."}
{"id": "PMID:184523", "title": "Precision and accuracy of foundry dust exposure estimates from air sampling data.", "content": "Errors in the sampling methods and in the determination of respirable size quartz in foundry dust have been evaluated and discussed. In general, the total precision of dust sampling and analysis was better than 20%. The term \"exposure dose\" is introduced and defined. The temporal variation associated with measuring exposure dose is assessed with reference to the use of a log-normal distribution of air sampling results. The logarithmic standard deviations of dust concentrations at fixed sites and jobs are calculated.", "contents": "Precision and accuracy of foundry dust exposure estimates from air sampling data. Errors in the sampling methods and in the determination of respirable size quartz in foundry dust have been evaluated and discussed. In general, the total precision of dust sampling and analysis was better than 20%. The term \"exposure dose\" is introduced and defined. The temporal variation associated with measuring exposure dose is assessed with reference to the use of a log-normal distribution of air sampling results. The logarithmic standard deviations of dust concentrations at fixed sites and jobs are calculated."}
{"id": "PMID:184524", "title": "Dust exposure in Finnish foundries.", "content": "Dust measurements were made in 51 iron, 9 steel, and 8 nonferrous foundries, at which 4,316 foundrymen were working. The sampling lasted at least two entire shifts or work days continuously during various operations in each foundry. The dust samples were collected at fixed sites or in the breathing zones of the workers. The mass concentration was determined by weighing and the respirable dust fraction was separated by liquid sedimentation. The free silica content was determined by X-ray diffraction. In the study a total of 3,188 samples were collected in the foundries and 6,505 determinations were made in the laboratory. The results indicated a definite difference in the dust exposure during various operations. The highest dust exposures were found during furnace, cupola, and pouring ladle repair. During cleaning work, sand mixing, and shake-out operations excessive silica dust concentrations were also measured. The lowest dust concentrations were measured during melting and pouring operations. Moderate dust concentrations were measured during coremaking and molding operations. The results obtained during the same operations of iron and steel foundries were similar. The distribution of the workers into various exposure categories, the content of respirable dust and quartz, the correlation between respirable dust and total dust, and the correlation between respirable silica and total dust concentrations are discussed. Observations concerning dust suppression and control methods are briefly considered.", "contents": "Dust exposure in Finnish foundries. Dust measurements were made in 51 iron, 9 steel, and 8 nonferrous foundries, at which 4,316 foundrymen were working. The sampling lasted at least two entire shifts or work days continuously during various operations in each foundry. The dust samples were collected at fixed sites or in the breathing zones of the workers. The mass concentration was determined by weighing and the respirable dust fraction was separated by liquid sedimentation. The free silica content was determined by X-ray diffraction. In the study a total of 3,188 samples were collected in the foundries and 6,505 determinations were made in the laboratory. The results indicated a definite difference in the dust exposure during various operations. The highest dust exposures were found during furnace, cupola, and pouring ladle repair. During cleaning work, sand mixing, and shake-out operations excessive silica dust concentrations were also measured. The lowest dust concentrations were measured during melting and pouring operations. Moderate dust concentrations were measured during coremaking and molding operations. The results obtained during the same operations of iron and steel foundries were similar. The distribution of the workers into various exposure categories, the content of respirable dust and quartz, the correlation between respirable dust and total dust, and the correlation between respirable silica and total dust concentrations are discussed. Observations concerning dust suppression and control methods are briefly considered."}
{"id": "PMID:184525", "title": "The Finnish foundry project. Background and general methodology.", "content": "The general methodology of the Finnish foundry project is presented. The project comprised dust measurements from all Finnish iron and steel foundries and a sample of nonferrous foundries, measurements of chemicals used in most foundries, and a mortality, morbidity and turnover study of active and retired foundry workers. The total budget of the project was Fmk 1,155,000 (+ 305,000). It was started in April 1972 and completed in May 1975. The project had the practical objective of developing recommendations for improvements in work conditions in individual foundries. More specific details of the methodology are reported in other communications.", "contents": "The Finnish foundry project. Background and general methodology. The general methodology of the Finnish foundry project is presented. The project comprised dust measurements from all Finnish iron and steel foundries and a sample of nonferrous foundries, measurements of chemicals used in most foundries, and a mortality, morbidity and turnover study of active and retired foundry workers. The total budget of the project was Fmk 1,155,000 (+ 305,000). It was started in April 1972 and completed in May 1975. The project had the practical objective of developing recommendations for improvements in work conditions in individual foundries. More specific details of the methodology are reported in other communications."}
{"id": "PMID:184531", "title": "Phosphatases in lake water: characterization of enzymes from phytoplankton and zooplankton by gel filtration.", "content": "Sephadex gel filtration was used to characterize phosphomonoesterases in two small takes in northern Sweden. Two fractions, here termed phosphatase A and phosphatase B, were found both as free enzymes and associated with seston. The activity of phosphatase A was correlated with the presence of algal biomass. Phosphatase B, on the other hand, was derived from zooplankton. Phosphate served as an effective inhibitor of phosphatase A but had no such effect on phosphatase B. Both fractions had pH optima between 6.5 and 7.0.", "contents": "Phosphatases in lake water: characterization of enzymes from phytoplankton and zooplankton by gel filtration. Sephadex gel filtration was used to characterize phosphomonoesterases in two small takes in northern Sweden. Two fractions, here termed phosphatase A and phosphatase B, were found both as free enzymes and associated with seston. The activity of phosphatase A was correlated with the presence of algal biomass. Phosphatase B, on the other hand, was derived from zooplankton. Phosphate served as an effective inhibitor of phosphatase A but had no such effect on phosphatase B. Both fractions had pH optima between 6.5 and 7.0."}
{"id": "PMID:184532", "title": "[Phosphorus and calcium metabolism in the normal pregnant woman].", "content": "The authors consider various aspects of calcium metabolism in pregnant women and the reciprocal influences of endogenous variations in the levels of parathormone, calcitonin, vitamin D, oestrogens and the interferences between calcium metabolism in the mother and that in the foetus. They note the precautions which should be taken for the neonatal calcium balance to be stable.", "contents": "[Phosphorus and calcium metabolism in the normal pregnant woman]. The authors consider various aspects of calcium metabolism in pregnant women and the reciprocal influences of endogenous variations in the levels of parathormone, calcitonin, vitamin D, oestrogens and the interferences between calcium metabolism in the mother and that in the foetus. They note the precautions which should be taken for the neonatal calcium balance to be stable."}
{"id": "PMID:184533", "title": "[Chronic urticarial lesions and macroglobulinemia. Apropos of 5 cases].", "content": "The authors report 5 cases whose main characteristics appeared very similar. Constantly, they found the same skin signs, urticaria without pruritus, recurring over a long period. The latter was accompanied by a very high E.S.R. and immuno-electrophoresis showed, in all cases, an increase in monoclonal IgB, permitting one to make the diagnosis of macroglobulinemia. In four cases out of five, this clinical picture was accompanied by bony pain associated with radiological signs of condensation. The symptoms were accompanied by prolonged fever and lymphadenopathy. After being well tolerated for a long period, the disease may become worse and lead to death. Thus this seems to be a true disease entity?", "contents": "[Chronic urticarial lesions and macroglobulinemia. Apropos of 5 cases]. The authors report 5 cases whose main characteristics appeared very similar. Constantly, they found the same skin signs, urticaria without pruritus, recurring over a long period. The latter was accompanied by a very high E.S.R. and immuno-electrophoresis showed, in all cases, an increase in monoclonal IgB, permitting one to make the diagnosis of macroglobulinemia. In four cases out of five, this clinical picture was accompanied by bony pain associated with radiological signs of condensation. The symptoms were accompanied by prolonged fever and lymphadenopathy. After being well tolerated for a long period, the disease may become worse and lead to death. Thus this seems to be a true disease entity?"}
{"id": "PMID:184534", "title": "[Paradoxical effect of forced inspiration: a new characteristic of asthmatic disease?].", "content": "In normal subjects, forced inspiration may dilate the bronchi and be considered as a defence or compensatory reaction in certain cases. In asthma, forced inspiration has the opposite effect. Bronchospasm occurs or becomes worse, usually moderately and transiently, but sometimes to a marked and lasting degree. These reactions may be prevented by anticholinergic and sympathomimetic drugs. They should be avoided and one should thus prohibit the manoeuvres which trigger them off. One should take them into consideration during respiratory function tests. This paradoxical effect of forced inspiration seems to exist to various degrees in most asthmatic patients, it may be considered as a diagnostic sign of asthma.", "contents": "[Paradoxical effect of forced inspiration: a new characteristic of asthmatic disease?]. In normal subjects, forced inspiration may dilate the bronchi and be considered as a defence or compensatory reaction in certain cases. In asthma, forced inspiration has the opposite effect. Bronchospasm occurs or becomes worse, usually moderately and transiently, but sometimes to a marked and lasting degree. These reactions may be prevented by anticholinergic and sympathomimetic drugs. They should be avoided and one should thus prohibit the manoeuvres which trigger them off. One should take them into consideration during respiratory function tests. This paradoxical effect of forced inspiration seems to exist to various degrees in most asthmatic patients, it may be considered as a diagnostic sign of asthma."}
{"id": "PMID:184538", "title": "[Calcium metabolism after the menopause].", "content": "The authors recall the antagonism between estradiol and parathormone. Estradiol tends to lower serum calcium and fix calcium in the bones as shown by one of us 25 years ago. The mechanism of this action of estrogen on calcium metabolism has been determined by numerous authors but some points are still not clear, e.g. the interferences between estrogen and calcitonin. Classically, parathormone is known to increase bony reabsorption and raise serum calcium. After the menopause the gradual reduction in estradiol secretion leads to post-menopausal osteoporosis. It is better to administer estrogens prophylactically to women after the menopause provided a cervical smear and mammography have been carried out to eliminate latent carcinoma of the breast or uterine cervix.", "contents": "[Calcium metabolism after the menopause]. The authors recall the antagonism between estradiol and parathormone. Estradiol tends to lower serum calcium and fix calcium in the bones as shown by one of us 25 years ago. The mechanism of this action of estrogen on calcium metabolism has been determined by numerous authors but some points are still not clear, e.g. the interferences between estrogen and calcitonin. Classically, parathormone is known to increase bony reabsorption and raise serum calcium. After the menopause the gradual reduction in estradiol secretion leads to post-menopausal osteoporosis. It is better to administer estrogens prophylactically to women after the menopause provided a cervical smear and mammography have been carried out to eliminate latent carcinoma of the breast or uterine cervix."}
{"id": "PMID:184539", "title": "[Cerebral metastases and their revealing forms in a series of 156 cases. Contribution of cerebral scintigraphy to the diagnosis and indications for surgery].", "content": "This series of 156 cases of brain metastases collected over a period of 14 years may be divided up into 65 considered as multiple following further investigation and thus refused for surgery, and 91 considered as simple and operated on. Our conclusions are very similar to those presented recently to the French Society of Neurosurgery. Emphasis is however placed on the frequency of metastases which are the first sign of cancer and thus resemble a cerebral tumour. Postoperatively the primary tumour continues to develop for it is often not found. Even under these conditions, a single metastasis should lead to operation and it may be distinguished from multiple metastases by a brain scan together with angiography which often permit not only the diagnosis of malignant tumour but also its secondary nature. The scan was positive in 85% of our 78 cases including 20 gamma-encephalographies and 58 angioscans. The diagnosis of metastases was possible in only 57% where as other authors have accorded more specificity to this investigation.", "contents": "[Cerebral metastases and their revealing forms in a series of 156 cases. Contribution of cerebral scintigraphy to the diagnosis and indications for surgery]. This series of 156 cases of brain metastases collected over a period of 14 years may be divided up into 65 considered as multiple following further investigation and thus refused for surgery, and 91 considered as simple and operated on. Our conclusions are very similar to those presented recently to the French Society of Neurosurgery. Emphasis is however placed on the frequency of metastases which are the first sign of cancer and thus resemble a cerebral tumour. Postoperatively the primary tumour continues to develop for it is often not found. Even under these conditions, a single metastasis should lead to operation and it may be distinguished from multiple metastases by a brain scan together with angiography which often permit not only the diagnosis of malignant tumour but also its secondary nature. The scan was positive in 85% of our 78 cases including 20 gamma-encephalographies and 58 angioscans. The diagnosis of metastases was possible in only 57% where as other authors have accorded more specificity to this investigation."}
{"id": "PMID:184542", "title": "[Effects of asbestos on respiratory pathology. 27 cases observed in 6 years in a pneumo-phthisiology department in Nantes].", "content": "A search for respiratory disease due to asbestos permitted the authors, during a review of 6 years' activity on a Chest Unit in Nantes, to collect 27 cases which represents 2.4% of all cases examined. They were male subjects usually aged about 60 years exposed to dust mildly but continuously during a long career as metal workers, mainly in the shipyards. Pleural involvement was constant, usually limited to characteristic pleural calcifications which were well tolerated. Two cases of asbestos pleurisy were diagnosed, but above all we noted 7 cases of mesothelioma with a very poor prognosis. It is difficult to say whether asbestos is responsible for bronchial carcinoma but we noted two cases in patients with calcifications. The authors emphasise the necessity for revision of the table of occupational diseases which does not yet include pleural disease due to asbestos.", "contents": "[Effects of asbestos on respiratory pathology. 27 cases observed in 6 years in a pneumo-phthisiology department in Nantes]. A search for respiratory disease due to asbestos permitted the authors, during a review of 6 years' activity on a Chest Unit in Nantes, to collect 27 cases which represents 2.4% of all cases examined. They were male subjects usually aged about 60 years exposed to dust mildly but continuously during a long career as metal workers, mainly in the shipyards. Pleural involvement was constant, usually limited to characteristic pleural calcifications which were well tolerated. Two cases of asbestos pleurisy were diagnosed, but above all we noted 7 cases of mesothelioma with a very poor prognosis. It is difficult to say whether asbestos is responsible for bronchial carcinoma but we noted two cases in patients with calcifications. The authors emphasise the necessity for revision of the table of occupational diseases which does not yet include pleural disease due to asbestos."}
{"id": "PMID:184543", "title": "[Clinical and statistical study of 100 vitiligo patients. I. Etiologic factors and clinical study].", "content": "A study of the etiological factors in 100 cases of vitiligo showed female predominance (59%) variable age of onset, absence of radial factor, moderate influence of psychological, physical or endocrine factors, the large number of subjects belonging to group B, a family history in 18% of cases. The morphology site and course of the lesions were also studied. There was no significant correlation between the course of the disease and the various etiological and clinical parameters studied.", "contents": "[Clinical and statistical study of 100 vitiligo patients. I. Etiologic factors and clinical study]. A study of the etiological factors in 100 cases of vitiligo showed female predominance (59%) variable age of onset, absence of radial factor, moderate influence of psychological, physical or endocrine factors, the large number of subjects belonging to group B, a family history in 18% of cases. The morphology site and course of the lesions were also studied. There was no significant correlation between the course of the disease and the various etiological and clinical parameters studied."}
{"id": "PMID:184544", "title": "[Streptozotocin and malignant insulinomas. Apropos of the case. Review of the literature].", "content": "In spite of possible toxicity streptozotocin now appears to be the best treatment for malignant islet cell tumour with liver metastases, i.e. inoperable tumours with a poor prognosis either due to extension of the tumour itself or due to hypoglycemic attacks. Out of about 60 patients thus treated, 1 to 2 years survival were obtained. 22 out of 52 patients reported by Broder and Carter are still alive and one may estimate the overall percentage of favourable results at 65%. On the other hand out of another 100 patients treated elsewhere with this antineoplastic agent, only a few cases of carcinoid tumour gave encouraging results. The course of the others was not modified significantly.", "contents": "[Streptozotocin and malignant insulinomas. Apropos of the case. Review of the literature]. In spite of possible toxicity streptozotocin now appears to be the best treatment for malignant islet cell tumour with liver metastases, i.e. inoperable tumours with a poor prognosis either due to extension of the tumour itself or due to hypoglycemic attacks. Out of about 60 patients thus treated, 1 to 2 years survival were obtained. 22 out of 52 patients reported by Broder and Carter are still alive and one may estimate the overall percentage of favourable results at 65%. On the other hand out of another 100 patients treated elsewhere with this antineoplastic agent, only a few cases of carcinoid tumour gave encouraging results. The course of the others was not modified significantly."}
{"id": "PMID:184551", "title": "Adaptation of cells derived from human malignant tumours to growth in vitro.", "content": "Forty-five human malignant tumour specimens were cultivated in vitro in an attempt to determine the necessary conditions for tumour cell maintenance and to establish permanently-growing cell lines. Continuously-growing cultures were derived from five tumours, including carcinomas of the oesophagus and colon, a hepatoma, a mesothelioma and a retroperitoneal sarcoma. The carcinoma of the oesophagus and the hepatoma, which have adapted fully to in vitro conditions, can be regarded as established cell lines.", "contents": "Adaptation of cells derived from human malignant tumours to growth in vitro. Forty-five human malignant tumour specimens were cultivated in vitro in an attempt to determine the necessary conditions for tumour cell maintenance and to establish permanently-growing cell lines. Continuously-growing cultures were derived from five tumours, including carcinomas of the oesophagus and colon, a hepatoma, a mesothelioma and a retroperitoneal sarcoma. The carcinoma of the oesophagus and the hepatoma, which have adapted fully to in vitro conditions, can be regarded as established cell lines."}
{"id": "PMID:184552", "title": "Occurrence of primary hepatocellular cancer and peliosis hepatis after treatment with androgenic steroids.", "content": "Three patients are reported in whom treatment of Fanconi's anaemia with androgenic steroids was complicated by the development of either primary hepatocellular cancer (PHC) or peliosis hepatis. The first, a White woman aged 34 years, was found to have PHC after receiving first methyltestosterone and then oxymetholone for a total period of 7 years. She died 4 months after the diagnosis was made. The other 2 patients were White children who presented with peliosis hepatis after receiving methyltestosterone and oxymetholone for 8 years and oxymetholone for 5 years, respectively. Both died from their primary diseases shortly after oxymetholone treatment was discontinued. Possible pathogenic mechanisms involved in the development of these serious complications are discussed and the therapeutic dilemma raised by their occurrence is emphasised.", "contents": "Occurrence of primary hepatocellular cancer and peliosis hepatis after treatment with androgenic steroids. Three patients are reported in whom treatment of Fanconi's anaemia with androgenic steroids was complicated by the development of either primary hepatocellular cancer (PHC) or peliosis hepatis. The first, a White woman aged 34 years, was found to have PHC after receiving first methyltestosterone and then oxymetholone for a total period of 7 years. She died 4 months after the diagnosis was made. The other 2 patients were White children who presented with peliosis hepatis after receiving methyltestosterone and oxymetholone for 8 years and oxymetholone for 5 years, respectively. Both died from their primary diseases shortly after oxymetholone treatment was discontinued. Possible pathogenic mechanisms involved in the development of these serious complications are discussed and the therapeutic dilemma raised by their occurrence is emphasised."}
{"id": "PMID:184553", "title": "The chest radiograph in primary liver cancer: an analysis of 449 cases.", "content": "The value of plain chest radiography in the diagnosis of primary hepatocellular cancer (PHC) was assessed in 449 patients. An elevated right hemidiaphragm and pulmonary metastases were present in 11% and strongly suggest a diagnosis of PHC. In all, the right hemidiaphragm was raised in 30% of patients. Pulmonary metastases were present on admission in 19% of patients and appeared later in a further 6%. Secondary deposits were found in the lungs at necropsy in 52% of patients, compared with only 24% in whom there was radiological evidence of metastases during life. In 36% of patients chest radiographs were normal on admission.", "contents": "The chest radiograph in primary liver cancer: an analysis of 449 cases. The value of plain chest radiography in the diagnosis of primary hepatocellular cancer (PHC) was assessed in 449 patients. An elevated right hemidiaphragm and pulmonary metastases were present in 11% and strongly suggest a diagnosis of PHC. In all, the right hemidiaphragm was raised in 30% of patients. Pulmonary metastases were present on admission in 19% of patients and appeared later in a further 6%. Secondary deposits were found in the lungs at necropsy in 52% of patients, compared with only 24% in whom there was radiological evidence of metastases during life. In 36% of patients chest radiographs were normal on admission."}
{"id": "PMID:184555", "title": "Treatment of cerebral vasospasm by control of cyclic adenosine monophosphate.", "content": "Twelve patients with cerebral vasospasm following subarachnoid hemorrhage were treated with intravenous aminophylline and isoproterenol. After angiographic demonstration of spasm, all patients were begun on a continuous intravenous infusion of isoproterenol, 125 mug/hr, and aminophylline, 125 mg/hr, for a period of up to two weeks. The infusion was continued until there was clinical or angiographic evidence that spasm had diminished. Nine patients improved on this regimen and three remained unchanged. The use of isoproterenol and aminophylline is based on their effect on the enzymes responsible for the formation and degradation of cyclic adenosine monophosphate (cyclic AMP). An increase in cyclic AMP has been noted to produce relaxation of vascular smooth muscle. It is proposed that manipulation of these biochemical pathways may provide a method for influencing blood flow through cerebral vessels.", "contents": "Treatment of cerebral vasospasm by control of cyclic adenosine monophosphate. Twelve patients with cerebral vasospasm following subarachnoid hemorrhage were treated with intravenous aminophylline and isoproterenol. After angiographic demonstration of spasm, all patients were begun on a continuous intravenous infusion of isoproterenol, 125 mug/hr, and aminophylline, 125 mg/hr, for a period of up to two weeks. The infusion was continued until there was clinical or angiographic evidence that spasm had diminished. Nine patients improved on this regimen and three remained unchanged. The use of isoproterenol and aminophylline is based on their effect on the enzymes responsible for the formation and degradation of cyclic adenosine monophosphate (cyclic AMP). An increase in cyclic AMP has been noted to produce relaxation of vascular smooth muscle. It is proposed that manipulation of these biochemical pathways may provide a method for influencing blood flow through cerebral vessels."}
{"id": "PMID:184556", "title": "The surgical implications of estrophile protein estimations in carcinoma of the breast.", "content": "Assays of estrophile protein (ER) in 161 patients with no previous additive or ablative hormonal therapy have been analyzed; 47.2 percent were ER positive; 52.8 percent ER negative. A total of 37.5 percent of premenopausal and 50.8 percent of postmenopausal patients had ER-positive tumors. The effects of additive and ablaive hormonal therapy were observed in 75 patients; 63.5 percent of the ER-positive group and 8.6 percent of the ER-negative group responded, but the incidence in the ER-negative group is thought to be spuriously high. The level of the ER content in the ER-positive group did not influence the degree of response. The ER-negative group had a shorter life span after discovery of the tumor and was more likely to develop dominant visceral metastases. Of 15 patients followed with sequential ER assays after hormonal therapy (additive and/or ablative), 14 demonstrated substantial falls in ER levels but these did not correlate with the clinical response. Tumor assayed in nine patients after irradiation of the lesion contained no demonstrable ER. ER assays of breast cancer tissue proved to be a useful but imperfect tool in predicting clinical progress following hormonal maneuvers but some readings may be spuriously low due to imperfect techniques of measurement, prior exogenous hormonal administration or hormonal ablation, and previous irradiation of the tumor.", "contents": "The surgical implications of estrophile protein estimations in carcinoma of the breast. Assays of estrophile protein (ER) in 161 patients with no previous additive or ablative hormonal therapy have been analyzed; 47.2 percent were ER positive; 52.8 percent ER negative. A total of 37.5 percent of premenopausal and 50.8 percent of postmenopausal patients had ER-positive tumors. The effects of additive and ablaive hormonal therapy were observed in 75 patients; 63.5 percent of the ER-positive group and 8.6 percent of the ER-negative group responded, but the incidence in the ER-negative group is thought to be spuriously high. The level of the ER content in the ER-positive group did not influence the degree of response. The ER-negative group had a shorter life span after discovery of the tumor and was more likely to develop dominant visceral metastases. Of 15 patients followed with sequential ER assays after hormonal therapy (additive and/or ablative), 14 demonstrated substantial falls in ER levels but these did not correlate with the clinical response. Tumor assayed in nine patients after irradiation of the lesion contained no demonstrable ER. ER assays of breast cancer tissue proved to be a useful but imperfect tool in predicting clinical progress following hormonal maneuvers but some readings may be spuriously low due to imperfect techniques of measurement, prior exogenous hormonal administration or hormonal ablation, and previous irradiation of the tumor."}
{"id": "PMID:184557", "title": "Precise selection of breast cancer patients with bone metastasis for endocrine ablation.", "content": "To enhance the precision of selection of breast cancer patients with bone metastasis for endocrine ablation, 85 patients underwent a Levodopa test for 4 consecutives days. Assessment of the result of the test was made on the basis of thorough clinical evaluation, x-ray examination, and results of serum and skin tests as well as cancer receptor studies when tissue was available. Results of 23 surgical procedures were as follows: bilateral oophorectomy elicited good clinical response in five patients with positive preoperative Levodopa tests; one negative clinical response followed a negative Levodopa test; bilateral adrenaloophorectomy in nine patients elicited good response in seven who had positive Levodopa tests and negative responses in two patients who had negative Levodopa tests; bilateral adrenalectomy in eight patients elicited good response in five patients with positive Levodopa tests and negative responses in three who had negative Levodopa tests. There were no deaths and there was only one complication after operation. Levodopa testing appears to be an effective means for selection of patients with bone pain from recurrent breast cancer who will benefit from endocrine ablation. When the Levodopa test was negative for bone pain relief, endocrine ablation was of no benefit to the patient.", "contents": "Precise selection of breast cancer patients with bone metastasis for endocrine ablation. To enhance the precision of selection of breast cancer patients with bone metastasis for endocrine ablation, 85 patients underwent a Levodopa test for 4 consecutives days. Assessment of the result of the test was made on the basis of thorough clinical evaluation, x-ray examination, and results of serum and skin tests as well as cancer receptor studies when tissue was available. Results of 23 surgical procedures were as follows: bilateral oophorectomy elicited good clinical response in five patients with positive preoperative Levodopa tests; one negative clinical response followed a negative Levodopa test; bilateral adrenaloophorectomy in nine patients elicited good response in seven who had positive Levodopa tests and negative responses in two patients who had negative Levodopa tests; bilateral adrenalectomy in eight patients elicited good response in five patients with positive Levodopa tests and negative responses in three who had negative Levodopa tests. There were no deaths and there was only one complication after operation. Levodopa testing appears to be an effective means for selection of patients with bone pain from recurrent breast cancer who will benefit from endocrine ablation. When the Levodopa test was negative for bone pain relief, endocrine ablation was of no benefit to the patient."}
{"id": "PMID:184559", "title": "Fibrous histiocytoma of the lung.", "content": "A case of asymptomatic fibrous histiocytoma of the lung is described in a 14-year-old girl. A left thoracotomy was performed followed by partial resection of the lingula. Postoperative progress was uneventful.", "contents": "Fibrous histiocytoma of the lung. A case of asymptomatic fibrous histiocytoma of the lung is described in a 14-year-old girl. A left thoracotomy was performed followed by partial resection of the lingula. Postoperative progress was uneventful."}
{"id": "PMID:184560", "title": "Metabolic properties of human platelet membranes. II. Thrombin-induced phosphorylation of membrane lipids and demonstration of phosphorylating enzymes in the platelet membrane.", "content": "Washed human platelets have been labeled with either 32Pi or glycerol-1-14C and the distribution of the label in the phospholipids determined. 32Pi was introduced primarily into polyphosphoinositides, i.e. di- and triphosphoinositide, whereas the label from glycerol which indicates de novo synthesis of lipid molecules did not appear in these phospholipids. In the course of thrombin-induced aggregation and release the phosphate incorporation into phosphatic acid, di- and triphosphoinositide was rapidly stimulated in parallel to the platelet reaction. The incorporation of glycerol did not change under the same conditions. It is concluded that phosphoinositides with rapid incorporation of phosphate groups are not as rapidly synthesized de novo and presumably form a separate phospholipid pool in the platelets. Only the phosphorylating reactions are stimulated by the thrombin aggregation. The necessary enzymes for these reactions, namely diglyceride kinase, phosphatidylinositol kinase, and phosphatidylinositol-phosphate kinase all can be shown to be associated with a well characterized platelet membrane fraction.", "contents": "Metabolic properties of human platelet membranes. II. Thrombin-induced phosphorylation of membrane lipids and demonstration of phosphorylating enzymes in the platelet membrane. Washed human platelets have been labeled with either 32Pi or glycerol-1-14C and the distribution of the label in the phospholipids determined. 32Pi was introduced primarily into polyphosphoinositides, i.e. di- and triphosphoinositide, whereas the label from glycerol which indicates de novo synthesis of lipid molecules did not appear in these phospholipids. In the course of thrombin-induced aggregation and release the phosphate incorporation into phosphatic acid, di- and triphosphoinositide was rapidly stimulated in parallel to the platelet reaction. The incorporation of glycerol did not change under the same conditions. It is concluded that phosphoinositides with rapid incorporation of phosphate groups are not as rapidly synthesized de novo and presumably form a separate phospholipid pool in the platelets. Only the phosphorylating reactions are stimulated by the thrombin aggregation. The necessary enzymes for these reactions, namely diglyceride kinase, phosphatidylinositol kinase, and phosphatidylinositol-phosphate kinase all can be shown to be associated with a well characterized platelet membrane fraction."}
{"id": "PMID:184563", "title": "Modification of survival of gamma irradiated mice by adenosine nucleotides.", "content": "The administratio prior to irradiation of adenosine triphosphate (ATP) or other adenosine nucleotides, singly or in combination, increased the radioresistance of mice. Post-irradiation treatment with the adenosine nucleotides had no effect on the survival of the irradiated mice. Dose reduction factors of 2.32 could be obtained by pretreatment of mice with the following combination of protective agents: S-2(4-aminobutylamino)ethyl phosphorothioic acid(WR 2822), cysteamine (MEA) and ATP. Since cyclic AMP levels were unchangd in the spleen or gut by administration of cysteamine and other protectors it is unlikely that the increase in preotection was due to changes in cyclic AMP levles. The calcium salt of ATP provided a higher level of protection than the ATP alone, indicating that the protective mechanism of ATP is probably not related to anoxia.", "contents": "Modification of survival of gamma irradiated mice by adenosine nucleotides. The administratio prior to irradiation of adenosine triphosphate (ATP) or other adenosine nucleotides, singly or in combination, increased the radioresistance of mice. Post-irradiation treatment with the adenosine nucleotides had no effect on the survival of the irradiated mice. Dose reduction factors of 2.32 could be obtained by pretreatment of mice with the following combination of protective agents: S-2(4-aminobutylamino)ethyl phosphorothioic acid(WR 2822), cysteamine (MEA) and ATP. Since cyclic AMP levels were unchangd in the spleen or gut by administration of cysteamine and other protectors it is unlikely that the increase in preotection was due to changes in cyclic AMP levles. The calcium salt of ATP provided a higher level of protection than the ATP alone, indicating that the protective mechanism of ATP is probably not related to anoxia."}
{"id": "PMID:184564", "title": "Progesterone secretion by adrenal glands of hamsters and comparison of ACTH influence in rats and hamsters.", "content": "Studies were designed to determine a) if adrenal glands of hamsters secrete progesterone (PROG), b) the effects of adrenocritocotropin (ACTH) administration on adrenocortial function of rats and hamsters under the surgical conditions necessary for collection of adrenal venous blood from the left renal vein, and c) the effects of blood loss during sample collection. PROG was quantitated by the competitive protein-binding method after extraction and separation by sephadex LH-20 column chromatography. The presence of interfering quantities of androstenedione necessitated two column chromatographic steps. Glucocorticoids (11-OHCS) were determined fluorometrically. PROG was detected in adrenal venous plasma of female hamsters. The PROG concentration and secretory rate were 91 +/- 12 ng/ml and 4 +/- 1 ng/min, respectively, while the peripheral plasma level of the same animals was 2 +/- 0.2 ng/ml, indicating that the adrenal glands of female hamsters are capable of secreting PROG. ACTH administration increased PROG secretory rates in both hamsters (3 +/- 1 to 14 +/- 3 ng/min) and rats (62 +/- 9 to 152 +/- 32 ng/min) on estrus, as well as increasing the 11-OHCS secretory rate of hamsters (16 +/- 1 to 33 +/- 4 ng/min), but not of rats. The greater increase in PRCC than in 11-OHCS secretion may be related to excess PROG formation relative to the capacity of the 17alpha- or 21-hydroxylating enzyme systems. The adrenal venous PROG concentration and secretory rate of female hamsters infused with 10% dextran while collecting adrenal venous blood did not differ significantly from those of the non-infused animals, suggesting that this amount of blood loss (1 ml) does not influence PROG secretion.", "contents": "Progesterone secretion by adrenal glands of hamsters and comparison of ACTH influence in rats and hamsters. Studies were designed to determine a) if adrenal glands of hamsters secrete progesterone (PROG), b) the effects of adrenocritocotropin (ACTH) administration on adrenocortial function of rats and hamsters under the surgical conditions necessary for collection of adrenal venous blood from the left renal vein, and c) the effects of blood loss during sample collection. PROG was quantitated by the competitive protein-binding method after extraction and separation by sephadex LH-20 column chromatography. The presence of interfering quantities of androstenedione necessitated two column chromatographic steps. Glucocorticoids (11-OHCS) were determined fluorometrically. PROG was detected in adrenal venous plasma of female hamsters. The PROG concentration and secretory rate were 91 +/- 12 ng/ml and 4 +/- 1 ng/min, respectively, while the peripheral plasma level of the same animals was 2 +/- 0.2 ng/ml, indicating that the adrenal glands of female hamsters are capable of secreting PROG. ACTH administration increased PROG secretory rates in both hamsters (3 +/- 1 to 14 +/- 3 ng/min) and rats (62 +/- 9 to 152 +/- 32 ng/min) on estrus, as well as increasing the 11-OHCS secretory rate of hamsters (16 +/- 1 to 33 +/- 4 ng/min), but not of rats. The greater increase in PRCC than in 11-OHCS secretion may be related to excess PROG formation relative to the capacity of the 17alpha- or 21-hydroxylating enzyme systems. The adrenal venous PROG concentration and secretory rate of female hamsters infused with 10% dextran while collecting adrenal venous blood did not differ significantly from those of the non-infused animals, suggesting that this amount of blood loss (1 ml) does not influence PROG secretion."}
{"id": "PMID:184568", "title": "Acute haemorrhagic conjunctivitis and enterovirus 70 in Kenya.", "content": "The pandemic of acute haemorrhagic conjunctivitis that started in Ghana in 1969 and spread to many countries in Africa, Asia and Europe reached Kenya in April 1971. From one patient virus was isolated. This was possibly the first strain ever isolated of Enterovirus 70. Identification took time and was finished long after the publication of isolation of the new virus in Japan. Cross neutralization tests with the virus from Japan showed close relationship between the two. During a second epidemic in Kenya in 1974 many more strains of the virus were isolated. The history of isolation and identification and the clinical picture of the disease as seen in Kenya are described.", "contents": "Acute haemorrhagic conjunctivitis and enterovirus 70 in Kenya. The pandemic of acute haemorrhagic conjunctivitis that started in Ghana in 1969 and spread to many countries in Africa, Asia and Europe reached Kenya in April 1971. From one patient virus was isolated. This was possibly the first strain ever isolated of Enterovirus 70. Identification took time and was finished long after the publication of isolation of the new virus in Japan. Cross neutralization tests with the virus from Japan showed close relationship between the two. During a second epidemic in Kenya in 1974 many more strains of the virus were isolated. The history of isolation and identification and the clinical picture of the disease as seen in Kenya are described."}
{"id": "PMID:184569", "title": "Studies with bluetongue virus in Nigeria.", "content": "Using an agar gel diffusion test antibody evidence indicates that bluetongue virus is widely distributed in Nigeria and commonly infects cattle, sheep and goats. In a single dairy herd serological conversions were observed in both wet and dry seasons.", "contents": "Studies with bluetongue virus in Nigeria. Using an agar gel diffusion test antibody evidence indicates that bluetongue virus is widely distributed in Nigeria and commonly infects cattle, sheep and goats. In a single dairy herd serological conversions were observed in both wet and dry seasons."}
{"id": "PMID:184572", "title": "[Rare kidney tumours (author's transl)].", "content": "In 508 patients with tumours of the kidney, 14 rare neoplasms has been found. These are analyzed with regard to diagnosis, therapy, and prognosis.", "contents": "[Rare kidney tumours (author's transl)]. In 508 patients with tumours of the kidney, 14 rare neoplasms has been found. These are analyzed with regard to diagnosis, therapy, and prognosis."}
{"id": "PMID:184573", "title": "Papillary adenocarcinoma of prostate.", "content": "Papillary adenocarcinomas of the prostate are rare tumors which may arise from the prostatic ducts and the utricle; 2 cases are described. The diagnosis of these tumors is best established by cystourethroscopy and transurethral resection. The more common prostatic acinar adenocarcinoma is frequently associated with these tumors. The histopathologic recognition of papillary adenocarcinoma of the prostate and its differentiation from acinar adenocarcinoma is important since the natural history and response to treatment may be different.", "contents": "Papillary adenocarcinoma of prostate. Papillary adenocarcinomas of the prostate are rare tumors which may arise from the prostatic ducts and the utricle; 2 cases are described. The diagnosis of these tumors is best established by cystourethroscopy and transurethral resection. The more common prostatic acinar adenocarcinoma is frequently associated with these tumors. The histopathologic recognition of papillary adenocarcinoma of the prostate and its differentiation from acinar adenocarcinoma is important since the natural history and response to treatment may be different."}
{"id": "PMID:184574", "title": "Unusual presentation of Wilms' tumor.", "content": "A Wilms' tumor, completely filling the collecting system of a kidney, led to nonfunction of the involved kidney. Histologic examination proved absence of renal vein involvement. Review of our case material and discussions with other centers showed that this unusual presentation has been seen elsewhere.", "contents": "Unusual presentation of Wilms' tumor. A Wilms' tumor, completely filling the collecting system of a kidney, led to nonfunction of the involved kidney. Histologic examination proved absence of renal vein involvement. Review of our case material and discussions with other centers showed that this unusual presentation has been seen elsewhere."}
{"id": "PMID:184576", "title": "[Surgical treatment of patients with malignant non-epithelial tumors of the stomach].", "content": "Under study were the data obtained in 29 patients with malignant nonepithelial gastric tumors, which indicated a high incidence of this affection in persons under 50. Gastric reticulosarcomas are most frequently observed. The diagnosis is very difficult to establish both before and during laparatomy. Favourable late results were most frequently noted in patients subjected to radical surgical interventions. Radical and tentative laparotomies may be followed by chemo-or radiotherapy.", "contents": "[Surgical treatment of patients with malignant non-epithelial tumors of the stomach]. Under study were the data obtained in 29 patients with malignant nonepithelial gastric tumors, which indicated a high incidence of this affection in persons under 50. Gastric reticulosarcomas are most frequently observed. The diagnosis is very difficult to establish both before and during laparatomy. Favourable late results were most frequently noted in patients subjected to radical surgical interventions. Radical and tentative laparotomies may be followed by chemo-or radiotherapy."}
{"id": "PMID:184579", "title": "Spontaneous Pancreatic beta cell tumor in the rat. A light and electron microscopic study.", "content": "Fine structural study of a pancreatic neoplasm found at autopsy of a 27-month-old female Long-Evans rat showed that the tumor consisted of, and derived from beta cells of the islets of Langerhans.", "contents": "Spontaneous Pancreatic beta cell tumor in the rat. A light and electron microscopic study. Fine structural study of a pancreatic neoplasm found at autopsy of a 27-month-old female Long-Evans rat showed that the tumor consisted of, and derived from beta cells of the islets of Langerhans."}
{"id": "PMID:184582", "title": "Giant cell tumor of soft parts. An ultrastructural study.", "content": "The light-microscopic and ultrastructural findings in a case of so-called giant cell tumor of soft parts, localized at the dorsal side of the left foot of a 23-years-old male are described. An amputation of the lower extremity was performed and subsequently chemotherapy with adriamycin was given for 3 months. Despite the histology and cytologic malignant appearance and the evident vascular invasion, already present at the time of the first excision, the last known status 2 years later seems favorable. There are no pathologic lymph nodes in the groins and no signs of metastases on chest X-rays. From the electron-microscope study no definite conclusion can be drawn as regards the histogenesis of this tumor. we feel, as do others, that many of the principal mononuclear tumor cells are poorly differentiated mesenchymal cells. Some of the neoplastic cells, however, show ultrastructural features suggestive of chondro- or osteoblasts (a well-developed r.e.r. containing electron-dense material; multiple Golgi complexes; masses of glycogen; interdigitating cell membrane villi; cytoplasmic filaments; an extracellular amorphous matrix). Some of the larger tumor cells have the submicroscopic aspects of histiocytes as described in osseous, cutaneous, or pulmonary lesions of the histiocytosis X group. As yet undetermined cytoplasmic inclusion bodies constitute another rare observation in our material.", "contents": "Giant cell tumor of soft parts. An ultrastructural study. The light-microscopic and ultrastructural findings in a case of so-called giant cell tumor of soft parts, localized at the dorsal side of the left foot of a 23-years-old male are described. An amputation of the lower extremity was performed and subsequently chemotherapy with adriamycin was given for 3 months. Despite the histology and cytologic malignant appearance and the evident vascular invasion, already present at the time of the first excision, the last known status 2 years later seems favorable. There are no pathologic lymph nodes in the groins and no signs of metastases on chest X-rays. From the electron-microscope study no definite conclusion can be drawn as regards the histogenesis of this tumor. we feel, as do others, that many of the principal mononuclear tumor cells are poorly differentiated mesenchymal cells. Some of the neoplastic cells, however, show ultrastructural features suggestive of chondro- or osteoblasts (a well-developed r.e.r. containing electron-dense material; multiple Golgi complexes; masses of glycogen; interdigitating cell membrane villi; cytoplasmic filaments; an extracellular amorphous matrix). Some of the larger tumor cells have the submicroscopic aspects of histiocytes as described in osseous, cutaneous, or pulmonary lesions of the histiocytosis X group. As yet undetermined cytoplasmic inclusion bodies constitute another rare observation in our material."}
{"id": "PMID:184583", "title": "[Intracytoplasmic inclusions within cells of the breast and their diagnostic significance (author's transl)].", "content": "There were 700 tissue biopsies of the breast with and without carcinomas examined simultaneously by intraoperative histology and imprint cytology. In 20.2% of the cases with carcinoma the tumor cells showed peculiar intracytoplasmic inclusions, whereas in only 0.43% of the biopsies of the mamma without carcinoma such inclusions were to be found. Their morphologic variation and the histochemical pattern are discussed. It is pointed out that these intracytoplasmic inclusions may be a helpful histopathologic feature in the diagnosis of breast cancer.", "contents": "[Intracytoplasmic inclusions within cells of the breast and their diagnostic significance (author's transl)]. There were 700 tissue biopsies of the breast with and without carcinomas examined simultaneously by intraoperative histology and imprint cytology. In 20.2% of the cases with carcinoma the tumor cells showed peculiar intracytoplasmic inclusions, whereas in only 0.43% of the biopsies of the mamma without carcinoma such inclusions were to be found. Their morphologic variation and the histochemical pattern are discussed. It is pointed out that these intracytoplasmic inclusions may be a helpful histopathologic feature in the diagnosis of breast cancer."}
{"id": "PMID:184584", "title": "Cellular differentiations and structural characteristics in nasopharyngeal angiofibromas. An electron-microscopic study.", "content": "An electron-microscopic study of 9 nasopharyngeal angiofibromas was performed in order to elucidate the ultrastructural characteristics. Stromal fibroblasts and proliferating cells of the microvasculature were found. The stromal fibroblasts were subdivided into 3 different groups: (1) \"classical\" fibroblasts, (2) fibroblasts with histiocytelike features, and (3) fibroblasts with myoid features. By proliferation the cells of the capillary vessels change into stromal cells. A particular pattern of nuclei and dense intranuclear granules is only found in stromal fibroblasts. Consequently fibroblasts as well as cells of the microvasculature contribute to the pool of tumor cells.", "contents": "Cellular differentiations and structural characteristics in nasopharyngeal angiofibromas. An electron-microscopic study. An electron-microscopic study of 9 nasopharyngeal angiofibromas was performed in order to elucidate the ultrastructural characteristics. Stromal fibroblasts and proliferating cells of the microvasculature were found. The stromal fibroblasts were subdivided into 3 different groups: (1) \"classical\" fibroblasts, (2) fibroblasts with histiocytelike features, and (3) fibroblasts with myoid features. By proliferation the cells of the capillary vessels change into stromal cells. A particular pattern of nuclei and dense intranuclear granules is only found in stromal fibroblasts. Consequently fibroblasts as well as cells of the microvasculature contribute to the pool of tumor cells."}
{"id": "PMID:184585", "title": "Cellular origin of human pancreatic polypeptide (HPP) in endocrine tumours of the pancreas.", "content": "Pancreatic polypeptide (HPP) producing cells were detected in 23 out of 36 endocrine tumours of the pancreas. In all tumours shown to be producing two hormones it was possible to demonstrate two different cell types by immunocytochemistry and/or electron microscopy. The D1 cell was identified as the source of HPP in tumours.", "contents": "Cellular origin of human pancreatic polypeptide (HPP) in endocrine tumours of the pancreas. Pancreatic polypeptide (HPP) producing cells were detected in 23 out of 36 endocrine tumours of the pancreas. In all tumours shown to be producing two hormones it was possible to demonstrate two different cell types by immunocytochemistry and/or electron microscopy. The D1 cell was identified as the source of HPP in tumours."}
{"id": "PMID:184586", "title": "Interaction between ceruloplasmin and Sendai virus envelope components. Note i. Gel-filtration of Tween 20-solubilized envelope components.", "content": "Sindai virus was disrupted by treatment with different concentrations of Tween 20 in an alkaline medium and the variations in infectivity, turbidity, hemagglutinin, neuraminidase and hemolytic activities were followed up. Gel-filtration of virus envelope fragments obtained by disruption with 1% Tween 20 demonstrated their heterogeneity as regards shape, size and biological activity. The elution type, the ratio between hemagglutinin and neuraminidase activities and the affinity for red blood cells of the envelope fragments depend on the detergent concentration used for virus disruption and on the presence or absence of detergent in the eluent.", "contents": "Interaction between ceruloplasmin and Sendai virus envelope components. Note i. Gel-filtration of Tween 20-solubilized envelope components. Sindai virus was disrupted by treatment with different concentrations of Tween 20 in an alkaline medium and the variations in infectivity, turbidity, hemagglutinin, neuraminidase and hemolytic activities were followed up. Gel-filtration of virus envelope fragments obtained by disruption with 1% Tween 20 demonstrated their heterogeneity as regards shape, size and biological activity. The elution type, the ratio between hemagglutinin and neuraminidase activities and the affinity for red blood cells of the envelope fragments depend on the detergent concentration used for virus disruption and on the presence or absence of detergent in the eluent."}
{"id": "PMID:184587", "title": "Interaction between ceruloplasmin and Sendai virus envelope components. Note ii. Some characteristics of Tween 20-solubilized envelope components isolated by gel-filtration.", "content": "Biological activities of Tween 20-solubilized Sendai virus envelope differ according to the structure of the components obtained, which depends on: conditions of virus disruption, presence or absence of detergent during gel-filtration, duration of maintenance, type of fragments contained in the samples, and can be correlated neither with the size of fragments, nor with protein concentration.", "contents": "Interaction between ceruloplasmin and Sendai virus envelope components. Note ii. Some characteristics of Tween 20-solubilized envelope components isolated by gel-filtration. Biological activities of Tween 20-solubilized Sendai virus envelope differ according to the structure of the components obtained, which depends on: conditions of virus disruption, presence or absence of detergent during gel-filtration, duration of maintenance, type of fragments contained in the samples, and can be correlated neither with the size of fragments, nor with protein concentration."}
{"id": "PMID:184591", "title": "[Concentration of cytoplasmic RNA in the endometrium in trophoblastic disease].", "content": "The method of cytospectrophotometry was used to determine quantitatively the content of cytoplasmatic RNA in cells of endometrial glands in 28 females who suffered trophoblastic disease. It was found that during the first year after the disease the RNA content in the endometrium in patients, subjected to chemotherapy, was nearly twice as low as in females not treated with methotrexate. Within the same period the RNA content was mostly low in those, who suffered malignant forms of the disease and were injected larger doses of the substance, accordingly. If the duration of the disease was longer than a year, the RNA content in the endometrium in both methotrexate treated and not females proved to be nearly the same, in the former the content being reliably higher than the analogous value in the control group (10 females in a phase of normal menstrual cycle secretion not suffering hydatid mole). During the investigation a correlation was found between changes in the endometrial RNA content and the level of sex hromones excretion.", "contents": "[Concentration of cytoplasmic RNA in the endometrium in trophoblastic disease]. The method of cytospectrophotometry was used to determine quantitatively the content of cytoplasmatic RNA in cells of endometrial glands in 28 females who suffered trophoblastic disease. It was found that during the first year after the disease the RNA content in the endometrium in patients, subjected to chemotherapy, was nearly twice as low as in females not treated with methotrexate. Within the same period the RNA content was mostly low in those, who suffered malignant forms of the disease and were injected larger doses of the substance, accordingly. If the duration of the disease was longer than a year, the RNA content in the endometrium in both methotrexate treated and not females proved to be nearly the same, in the former the content being reliably higher than the analogous value in the control group (10 females in a phase of normal menstrual cycle secretion not suffering hydatid mole). During the investigation a correlation was found between changes in the endometrial RNA content and the level of sex hromones excretion."}
{"id": "PMID:184592", "title": "[Mechanism of the antitumor action of 1,6-di-o-methane-sulfonide-2,3-4,5-dianhydro-1-iditol].", "content": "Under study was the effect of the drug in question on the growth of ascitic tumor NK/Ly. The drug, depending on its dosage, was found to suppress the tumor growth both in its accelerated and delayed stage of development and to show an instant effect. Its efficacy in the dosage employed would have no stage selective character. DMDAI blocks DNA synthesis and presumably impairs the metabolism of RNA ingradients, playing an important role in the mitosis and synthesis of DNA.", "contents": "[Mechanism of the antitumor action of 1,6-di-o-methane-sulfonide-2,3-4,5-dianhydro-1-iditol]. Under study was the effect of the drug in question on the growth of ascitic tumor NK/Ly. The drug, depending on its dosage, was found to suppress the tumor growth both in its accelerated and delayed stage of development and to show an instant effect. Its efficacy in the dosage employed would have no stage selective character. DMDAI blocks DNA synthesis and presumably impairs the metabolism of RNA ingradients, playing an important role in the mitosis and synthesis of DNA."}
{"id": "PMID:184599", "title": "[Characteristics of the clinical picture and prognosis of insulinoma].", "content": "A case with insulinoma is reported, with initial malignant degeneration, diagnosed and operated 16 years ago. Six years later hypoglycemic attaks appeared again and lymph metastasis in good health a third surgical operation was performed because of repeated hypoglycemic attacks and a new metastasis from the insulinoma was found in the pancreas tail. The patients has no hypoglycemic phemonena 18 months after the last operation. Besides the long period of progress of the malignant degenerated insulinoma, not observed so far, certain peculiarities of the carbohydrate metabolism of that patient are stressed upon as well as the necessity of early diagnosis and timely surgical treatment of insulinoma.", "contents": "[Characteristics of the clinical picture and prognosis of insulinoma]. A case with insulinoma is reported, with initial malignant degeneration, diagnosed and operated 16 years ago. Six years later hypoglycemic attaks appeared again and lymph metastasis in good health a third surgical operation was performed because of repeated hypoglycemic attacks and a new metastasis from the insulinoma was found in the pancreas tail. The patients has no hypoglycemic phemonena 18 months after the last operation. Besides the long period of progress of the malignant degenerated insulinoma, not observed so far, certain peculiarities of the carbohydrate metabolism of that patient are stressed upon as well as the necessity of early diagnosis and timely surgical treatment of insulinoma."}
{"id": "PMID:184602", "title": "Seroimmunity of adult Ghanian hospital staff and their wards to poliomyelitis.", "content": "The antibody content of sera collected from 104 adult staff of the Korle Bu Teaching Hospital and 16 of their wards were studied by microtitre neutralization test to poliovirus types 1, 2 and 3. The immune status of the study population was highly satisfactory; there was only one (0.83%) out of the 120 persons studied without antibodies to all three poliovirus types. The percentage of sero-positive subjects to the individual poliovirus types, that is 1, 2 and 3 were 75.83%, 70.00% and 86.16% of the study population. Immunity in relation to age was also studied.", "contents": "Seroimmunity of adult Ghanian hospital staff and their wards to poliomyelitis. The antibody content of sera collected from 104 adult staff of the Korle Bu Teaching Hospital and 16 of their wards were studied by microtitre neutralization test to poliovirus types 1, 2 and 3. The immune status of the study population was highly satisfactory; there was only one (0.83%) out of the 120 persons studied without antibodies to all three poliovirus types. The percentage of sero-positive subjects to the individual poliovirus types, that is 1, 2 and 3 were 75.83%, 70.00% and 86.16% of the study population. Immunity in relation to age was also studied."}
{"id": "PMID:184604", "title": "Testing of antiviral compounds against Mengo virus infection of mice. A 2-step procedure of in vivo screening.", "content": "A 2-step procedure of screening of antiviral compounds in vivo is presented on the basis of standardized methods of both experimental examination and statistical analysis. The procedure uses the \"rate of protection\" R as the sole criterion of activity. In the first step, requiring a total of 40 mice, compounds with significant R are detected. Drugs producing R less than 15% are discarded. Compounds eliciting R larger than or equal to 15%, without significance, are examined in a second step, using again 40 mice, to decide whether the protective activity becomes significant employing a greater number of animals. The procedure works with relatively less expense with regard of the number of animals used and the time required. The procedure can be applied to test systems based on lethal infections as well as to test models for which the use of the \"rate of protection\" is relevant.", "contents": "Testing of antiviral compounds against Mengo virus infection of mice. A 2-step procedure of in vivo screening. A 2-step procedure of screening of antiviral compounds in vivo is presented on the basis of standardized methods of both experimental examination and statistical analysis. The procedure uses the \"rate of protection\" R as the sole criterion of activity. In the first step, requiring a total of 40 mice, compounds with significant R are detected. Drugs producing R less than 15% are discarded. Compounds eliciting R larger than or equal to 15%, without significance, are examined in a second step, using again 40 mice, to decide whether the protective activity becomes significant employing a greater number of animals. The procedure works with relatively less expense with regard of the number of animals used and the time required. The procedure can be applied to test systems based on lethal infections as well as to test models for which the use of the \"rate of protection\" is relevant."}
{"id": "PMID:184605", "title": "Characterization of a stable spheroplast type L-form of Proteus mirabilis D 52 as cell envelope mutant. II. Electronmicroscopic investigations.", "content": "The ultrastructural analysis of a stable spheroplast type L-form of Proteus mirabilis D 52 revealed characteristic alterations in the organization of the cell envelope including defective changes in the cell envelope structure as for instance the loss of a coherent murein layer, the loss of some components in the outer cell wall layer, the formation of small membraneous vesicles at the tips of loose extensions of the cell wall, a decrease in associations and bindings between wall and membrane, an extension of the periplasmic space, an increase in membrane defects, as well as a disturbed cell division causing unusual modes of multiplication and the formation of various intracellular structures like membrane complexes, characteristic sheet-like membraneous bodies, typical inclusion bodies, and defective phage structures, which all could not be observed in normal rod-shaped cells. The results of these investigations and of those given in a previous paper (Gumpert and Taubeneck 1975) show, that the stable spheroplast type L-form LD 52 B must be considered as a true cell envelope mutant in which the biosynthesis and structure of the cell envelope is altered genetically by one or several mutations whereas the main biochemical activities are the same like those of the parent bacterium. The profound alterations in the cell envelope system, however, lead to some changes in the whole cell organization, which apparently in turn cause disorders even in metabolic and biosynthetic processes not directly involved in the biosynthesis of the cell envelope.", "contents": "Characterization of a stable spheroplast type L-form of Proteus mirabilis D 52 as cell envelope mutant. II. Electronmicroscopic investigations. The ultrastructural analysis of a stable spheroplast type L-form of Proteus mirabilis D 52 revealed characteristic alterations in the organization of the cell envelope including defective changes in the cell envelope structure as for instance the loss of a coherent murein layer, the loss of some components in the outer cell wall layer, the formation of small membraneous vesicles at the tips of loose extensions of the cell wall, a decrease in associations and bindings between wall and membrane, an extension of the periplasmic space, an increase in membrane defects, as well as a disturbed cell division causing unusual modes of multiplication and the formation of various intracellular structures like membrane complexes, characteristic sheet-like membraneous bodies, typical inclusion bodies, and defective phage structures, which all could not be observed in normal rod-shaped cells. The results of these investigations and of those given in a previous paper (Gumpert and Taubeneck 1975) show, that the stable spheroplast type L-form LD 52 B must be considered as a true cell envelope mutant in which the biosynthesis and structure of the cell envelope is altered genetically by one or several mutations whereas the main biochemical activities are the same like those of the parent bacterium. The profound alterations in the cell envelope system, however, lead to some changes in the whole cell organization, which apparently in turn cause disorders even in metabolic and biosynthetic processes not directly involved in the biosynthesis of the cell envelope."}
{"id": "PMID:184609", "title": "[Biokinetic behavior and metabolic effect of fructose in high dose continuous infusion in the rat].", "content": "The steady-state blood level of fructose during 24 hours intravenous infusion in response to different doses follows saturation kinetics. Even after toxic doses of 1.5 g/kg/h no depletion of liver adenine nucleotides can be observed after 24 hours. In the kidneys, however, ATP, ADP and total adenine nucleotides were decreased after a dose of 1.5 g/kg/h of fructose. The blood glucose increased continuously at infusion rates of 1.5 g/kg/h. Inorganic phosphate in the blood increased at doses of 1.0 and 1.5 g/kg/h. The weight of the kidneys increased, presumably through water uptake. Urinary secretion was drastically reduced at doses above 1.0 g/kg/h. An appreciable activity of ketohexokinase can be demonstrated in the kidneys.", "contents": "[Biokinetic behavior and metabolic effect of fructose in high dose continuous infusion in the rat]. The steady-state blood level of fructose during 24 hours intravenous infusion in response to different doses follows saturation kinetics. Even after toxic doses of 1.5 g/kg/h no depletion of liver adenine nucleotides can be observed after 24 hours. In the kidneys, however, ATP, ADP and total adenine nucleotides were decreased after a dose of 1.5 g/kg/h of fructose. The blood glucose increased continuously at infusion rates of 1.5 g/kg/h. Inorganic phosphate in the blood increased at doses of 1.0 and 1.5 g/kg/h. The weight of the kidneys increased, presumably through water uptake. Urinary secretion was drastically reduced at doses above 1.0 g/kg/h. An appreciable activity of ketohexokinase can be demonstrated in the kidneys."}
{"id": "PMID:184610", "title": "[The diagnostic importance of low-density lipoprotein (LP-X) for the diagnosis of cholestasis].", "content": "Based on the clinical, biochemical and morphological examination of a selected group of patients, the following may be said about low-density lipoprotein (LP-X): The LP-X test 1. proves to be a reliable method of examination for diagnosing cholestasis. It is a quick and simple test; 2. has a highly significant statistical relationship (x2 = 31,7) to the histological results and other parameters indicating cholestasis; 3. does not, however, distinguish between intra- and extrahepatic cholestasis and positive results do not allow any conclusion as to the etiology of the icterus; 4. makes it possible to diagnose cases of cholestasis with aP activities not clinically manifest; 5. in borderline cases conclusions may be drawn from a combination of LP-X and aP results and, most of all, from LP-X and gamma-GT, a highly sensitive, specific and simple method of diagnosis. 6. diagnostic findings of still greater significance resulting from applying laboratory data indicating or precluding cholestasis may be derived from a prospective study with a larger group of patients, using the same parameters and taking the likelihood ratio into consideration.", "contents": "[The diagnostic importance of low-density lipoprotein (LP-X) for the diagnosis of cholestasis]. Based on the clinical, biochemical and morphological examination of a selected group of patients, the following may be said about low-density lipoprotein (LP-X): The LP-X test 1. proves to be a reliable method of examination for diagnosing cholestasis. It is a quick and simple test; 2. has a highly significant statistical relationship (x2 = 31,7) to the histological results and other parameters indicating cholestasis; 3. does not, however, distinguish between intra- and extrahepatic cholestasis and positive results do not allow any conclusion as to the etiology of the icterus; 4. makes it possible to diagnose cases of cholestasis with aP activities not clinically manifest; 5. in borderline cases conclusions may be drawn from a combination of LP-X and aP results and, most of all, from LP-X and gamma-GT, a highly sensitive, specific and simple method of diagnosis. 6. diagnostic findings of still greater significance resulting from applying laboratory data indicating or precluding cholestasis may be derived from a prospective study with a larger group of patients, using the same parameters and taking the likelihood ratio into consideration."}
{"id": "PMID:184612", "title": "[Cytoid bodies in basal cell epithelioma].", "content": "100 basal cell epitheliomas were surveyed for the presence of cytoid bodies by histological and histochemical techniques. By this means a differentiation of the following structures was possible: 1. Elastic globes were present in 32 specimens. Their localisation corresponded in part to the typical subepidermal situation, but invasive tumor growth resulted in their translocation into the deeper corium. 2. Civatte bodies were found in the dermoepidermal junction area in 16 cases. Similar structures were present within the tumor cell islands of 37 patients. 3. Russel bodies could be observed within the inflammatory peritumoral infiltrate containing numerous plasma cells in 30 specimens. 4. Clumpy or ovoid deposits of amyloid were present within the stroma of 41 epitheliomas, whereas no amyloid was found in the tumor cell islands.", "contents": "[Cytoid bodies in basal cell epithelioma]. 100 basal cell epitheliomas were surveyed for the presence of cytoid bodies by histological and histochemical techniques. By this means a differentiation of the following structures was possible: 1. Elastic globes were present in 32 specimens. Their localisation corresponded in part to the typical subepidermal situation, but invasive tumor growth resulted in their translocation into the deeper corium. 2. Civatte bodies were found in the dermoepidermal junction area in 16 cases. Similar structures were present within the tumor cell islands of 37 patients. 3. Russel bodies could be observed within the inflammatory peritumoral infiltrate containing numerous plasma cells in 30 specimens. 4. Clumpy or ovoid deposits of amyloid were present within the stroma of 41 epitheliomas, whereas no amyloid was found in the tumor cell islands."}
{"id": "PMID:184614", "title": "[Action of a new synthetic ACTH drug in psoriatic arthropathy].", "content": "In light of observations in 10 patients the author reports the results of a course of therapy with synthetic depot tetracosactide (SYNACTHEN DEPOT) in psoriatic arthritis. In 2 patients no improvement was evident, while in 3 patients temporary improvement was observed but the effect of the drug was inadequate except in combination. In 5 patients, following intramuscular administration of 1 mg without any other medication, improvement in the symptoms and the objective articular findings, where ankylosis was not present, was observed within a few hours and this improvement lasted for more than one week.", "contents": "[Action of a new synthetic ACTH drug in psoriatic arthropathy]. In light of observations in 10 patients the author reports the results of a course of therapy with synthetic depot tetracosactide (SYNACTHEN DEPOT) in psoriatic arthritis. In 2 patients no improvement was evident, while in 3 patients temporary improvement was observed but the effect of the drug was inadequate except in combination. In 5 patients, following intramuscular administration of 1 mg without any other medication, improvement in the symptoms and the objective articular findings, where ankylosis was not present, was observed within a few hours and this improvement lasted for more than one week."}
{"id": "PMID:184624", "title": "[Serum beta-lipoproteins following gynecologic surgery].", "content": "Authors have watched the changes of concentration of betalipoprotein after gynecological operations, on a large group of patients. The task of this work was to prove the existence of postcastration dyslipoproteinaemia, which had been proved in a smaller group by complex laboratory method. They have proved, using the Burstein's method, the development of dislipoproteinaemia in a larger number of vases after operation with bilateral ovarioectomy.", "contents": "[Serum beta-lipoproteins following gynecologic surgery]. Authors have watched the changes of concentration of betalipoprotein after gynecological operations, on a large group of patients. The task of this work was to prove the existence of postcastration dyslipoproteinaemia, which had been proved in a smaller group by complex laboratory method. They have proved, using the Burstein's method, the development of dislipoproteinaemia in a larger number of vases after operation with bilateral ovarioectomy."}
{"id": "PMID:184625", "title": "[Anatomical and clinical deliberations on the phyllodes tumor of the breast].", "content": "The authors report on three phyllod Tumours of the breast, two benign and one malignant conditions. They insist on the histological aspect of the tumour, underlining that in the benign forme both, epithelial and mesenchymal components does not present atypies, while in the malignant form only the mesenchymal component gets malign sarcomatous character. The microscopic aspect of the tumour and its clinical evolution are suspicious. The diagnosis can be specified only by the histopathological examination. The origin of the phyllod tumour is not clear and the authors discuss the possibility of its development upon a preexistent tumour, specifically on a fibroadenoma of the breast. The treatment is guided by the microscopic appearances. Generally they perform the ablation of the tumour when its dimensions are not greater then 10 cm. and the simple mastectomy when its diameter exceeds this dimension.", "contents": "[Anatomical and clinical deliberations on the phyllodes tumor of the breast]. The authors report on three phyllod Tumours of the breast, two benign and one malignant conditions. They insist on the histological aspect of the tumour, underlining that in the benign forme both, epithelial and mesenchymal components does not present atypies, while in the malignant form only the mesenchymal component gets malign sarcomatous character. The microscopic aspect of the tumour and its clinical evolution are suspicious. The diagnosis can be specified only by the histopathological examination. The origin of the phyllod tumour is not clear and the authors discuss the possibility of its development upon a preexistent tumour, specifically on a fibroadenoma of the breast. The treatment is guided by the microscopic appearances. Generally they perform the ablation of the tumour when its dimensions are not greater then 10 cm. and the simple mastectomy when its diameter exceeds this dimension."}
{"id": "PMID:184627", "title": "[Immunologic reactions to tissue antigens in patients with different stages of cerebral atherosclerosis].", "content": "The results of the conducted studies testify to the existence of a certain correlation between the stage of the pathological process and immunological reactions to brain antigens and vessels in patients with cerebral atherosclerosis. In the I and II stages of cerebral atherosclerosis there is a certain predominance of seropositive reactions to brain beta-lipoproteids. In transient disorders of brain circulation there were prevalent reactions to water soluble proteins of the vascular tissue. In patients with residual symptoms of ischemic strokes the most frequent findings were seropositive reactions to brain proteins and beta-lipoproteids.", "contents": "[Immunologic reactions to tissue antigens in patients with different stages of cerebral atherosclerosis]. The results of the conducted studies testify to the existence of a certain correlation between the stage of the pathological process and immunological reactions to brain antigens and vessels in patients with cerebral atherosclerosis. In the I and II stages of cerebral atherosclerosis there is a certain predominance of seropositive reactions to brain beta-lipoproteids. In transient disorders of brain circulation there were prevalent reactions to water soluble proteins of the vascular tissue. In patients with residual symptoms of ischemic strokes the most frequent findings were seropositive reactions to brain proteins and beta-lipoproteids."}
{"id": "PMID:184628", "title": "On the selectivity of aryl hydrocarbon hydroxylase induction after 3-methylcholanthrene pretreatment.", "content": "The development of aryl hydrocarbon (benzo(a)pyren)hydroxylase (AHH), succinate dehydrogenase and glucose-b-phosphatase activities in the liver and the kidney and of liver weight and glycogen were investigated in 7-day-old rats treated i.p. with 1, 10, and 100 mg 3-methylcholanthrene (MC)/kg body weight. 3-MC highly specifically influenced the AHH activity, which was increased dose dependent. The higher the dose, the higher and the longer was the induction effect. The other biochemical parameters investigated were not influenced. At the maximum of the induction effect after pretreatment with the highest dose of 3MC no morphological alterations in the liver could be observed by light and electron microscopy. Therefore the 3-MC mediated AHH induction seems to be a suitable model for the examination of dose dependent inducer-inhibitor interactions in the intact animal.", "contents": "On the selectivity of aryl hydrocarbon hydroxylase induction after 3-methylcholanthrene pretreatment. The development of aryl hydrocarbon (benzo(a)pyren)hydroxylase (AHH), succinate dehydrogenase and glucose-b-phosphatase activities in the liver and the kidney and of liver weight and glycogen were investigated in 7-day-old rats treated i.p. with 1, 10, and 100 mg 3-methylcholanthrene (MC)/kg body weight. 3-MC highly specifically influenced the AHH activity, which was increased dose dependent. The higher the dose, the higher and the longer was the induction effect. The other biochemical parameters investigated were not influenced. At the maximum of the induction effect after pretreatment with the highest dose of 3MC no morphological alterations in the liver could be observed by light and electron microscopy. Therefore the 3-MC mediated AHH induction seems to be a suitable model for the examination of dose dependent inducer-inhibitor interactions in the intact animal."}
{"id": "PMID:184629", "title": "Evidence for cyclic AMP-dependent protein kinase activity in isolated guinea pig and rat liver mitochondria.", "content": "Purified preparations of guinea pig and rat liver mitochondria contain considerable latent cAMP-dependent protein kinase activity that is revealed by treatment with 1% Triton X-100. The solubilized kinase was partly purified by DEAE-cellulose chromatography. It accepts protein in the washed Triton-extracted mitochondria as substrate.", "contents": "Evidence for cyclic AMP-dependent protein kinase activity in isolated guinea pig and rat liver mitochondria. Purified preparations of guinea pig and rat liver mitochondria contain considerable latent cAMP-dependent protein kinase activity that is revealed by treatment with 1% Triton X-100. The solubilized kinase was partly purified by DEAE-cellulose chromatography. It accepts protein in the washed Triton-extracted mitochondria as substrate."}
{"id": "PMID:184630", "title": "[Spectroscopic investigatons on the structural thermal stability of leucine aminopeptidase. ESR, CD and fluorescence studies].", "content": "The thermal behaviour of leucine aminopeptidase (LAP, EC: 3.4.11.1) from bovine eye lens has been investigated in the temperature region 20--70 degrees C by spin-labelling of SH-groups (ESR), by CD and by fluorescence of tryptophane residues. Enzymatic activity of LAP was compared with spectroscopic data in this temperature region. From 20-60 degrees C the structural parts (alpha, beta, random coil) estimated from CD spectra remain unchanged. Within 20-55 degrees C no irreversible exposure of tryptophane residues takes place. In both types of spin-labelled LAP the strong immobilizing environment of the label retains its highly ordered structure up to 55 degrees C. Reversible changes of mobility and polarity of the environment of the label induced by temperature within 20-50 degrees C do not reduce the enzymatic activity and are regarded as local loosening of ordered structure. At 65 degrees C strong precipitation occurs. From 55 degrees C to 65 degrees C tryptophane residues are irreversibly exposed. The highly ordered environment of the label is destroyed about 55 degrees C, and a considerable amount of spin label molecules is reduced at the NO group by exposed SH groups. The above mentioned local loosening of structure becomes irreversible at 60 degrees C. The environment of both labels dominating above 60 degrees C is highly mobile and strongly polar and represents an extensively unfolded conformation. Until 60 degrees C no essential disordering of protein structure leading to a decrease of enzymatic activity occurs. Above 60 degrees C a sharp breakdown of ordered structures takes place, which is accompanied by a strong diminution of enzymatic activity.", "contents": "[Spectroscopic investigatons on the structural thermal stability of leucine aminopeptidase. ESR, CD and fluorescence studies]. The thermal behaviour of leucine aminopeptidase (LAP, EC: 3.4.11.1) from bovine eye lens has been investigated in the temperature region 20--70 degrees C by spin-labelling of SH-groups (ESR), by CD and by fluorescence of tryptophane residues. Enzymatic activity of LAP was compared with spectroscopic data in this temperature region. From 20-60 degrees C the structural parts (alpha, beta, random coil) estimated from CD spectra remain unchanged. Within 20-55 degrees C no irreversible exposure of tryptophane residues takes place. In both types of spin-labelled LAP the strong immobilizing environment of the label retains its highly ordered structure up to 55 degrees C. Reversible changes of mobility and polarity of the environment of the label induced by temperature within 20-50 degrees C do not reduce the enzymatic activity and are regarded as local loosening of ordered structure. At 65 degrees C strong precipitation occurs. From 55 degrees C to 65 degrees C tryptophane residues are irreversibly exposed. The highly ordered environment of the label is destroyed about 55 degrees C, and a considerable amount of spin label molecules is reduced at the NO group by exposed SH groups. The above mentioned local loosening of structure becomes irreversible at 60 degrees C. The environment of both labels dominating above 60 degrees C is highly mobile and strongly polar and represents an extensively unfolded conformation. Until 60 degrees C no essential disordering of protein structure leading to a decrease of enzymatic activity occurs. Above 60 degrees C a sharp breakdown of ordered structures takes place, which is accompanied by a strong diminution of enzymatic activity."}
{"id": "PMID:184631", "title": "Dissociation and rate constants of some human liver alcohol dehydrogenase isoenzymes.", "content": "ADH from human liver forms binary complexes with NADH, associated with a blue shift of the peak of the fluorescence emission of NADH. The wavelength shift is the same for all isoenzymes but the accompanying intensification of the fluorescence is different. The fluorescence is further increased by the formation of the very tight ternary enzyme-NADH-isobutyramide complexes. These properties are similar to those for the horse liver ADH, as well as the molecular weight of E=40 000 per active site of the dimer molecule (EE). \"Stopped-flow\" determined velocity constants (ER in equilibrium E+R) were found to be in good agreement with ethanol activity constants previously determined by activity measurement, confirming the validity of the ordered ternary complex mechanism also for the human ADH. No single isoenzyme activity as high as that reported by Mourad and Woronick or Drum has been found.", "contents": "Dissociation and rate constants of some human liver alcohol dehydrogenase isoenzymes. ADH from human liver forms binary complexes with NADH, associated with a blue shift of the peak of the fluorescence emission of NADH. The wavelength shift is the same for all isoenzymes but the accompanying intensification of the fluorescence is different. The fluorescence is further increased by the formation of the very tight ternary enzyme-NADH-isobutyramide complexes. These properties are similar to those for the horse liver ADH, as well as the molecular weight of E=40 000 per active site of the dimer molecule (EE). \"Stopped-flow\" determined velocity constants (ER in equilibrium E+R) were found to be in good agreement with ethanol activity constants previously determined by activity measurement, confirming the validity of the ordered ternary complex mechanism also for the human ADH. No single isoenzyme activity as high as that reported by Mourad and Woronick or Drum has been found."}
{"id": "PMID:184633", "title": "Medullary thyroid carcinoma: ectopic production of peptides with ACTH-like, corticotrophin releasing factor-like and prolactin production-stimulating activities.", "content": "A 45-year-old women had medullary tyroid carcinoma associated with Cushing's syndrome and galactorrhoea. Elevated plasma immunoreactive ACTH and cortisol were partially suppressed by intravenous dexamethasone, appreciably raised by lysine vasopressin, and urinary excretion of 17-oxogenic steroids slightly elevated by metyrapone. A large arterio-venous increase in plasma corticotrophin releasing factor-like activity across the thyroid gland was observed and tumour tissue contained corticotrophin releasing factor-like activity. Biologically active ACTH was not detected in tumour extracts before incubation with trypsin, but after trypsinization a value of 3.2 mU per gram was obtained. Arterial plasma contained biologically active ACTH (1.5 mU/100 ml) prior to trypsinization. Venous effluent from the thyroid gland contained biologically active (9.6 mU/100 ml) and immunoreactive ACTH (970 pg/ml) before trypsinization. Tumour extracts also contained prolactin production-stimulating activity. These findings can explain the Cushing's syndrome and the galactorrhoea both of which disappeared completely after thyroidectomy.", "contents": "Medullary thyroid carcinoma: ectopic production of peptides with ACTH-like, corticotrophin releasing factor-like and prolactin production-stimulating activities. A 45-year-old women had medullary tyroid carcinoma associated with Cushing's syndrome and galactorrhoea. Elevated plasma immunoreactive ACTH and cortisol were partially suppressed by intravenous dexamethasone, appreciably raised by lysine vasopressin, and urinary excretion of 17-oxogenic steroids slightly elevated by metyrapone. A large arterio-venous increase in plasma corticotrophin releasing factor-like activity across the thyroid gland was observed and tumour tissue contained corticotrophin releasing factor-like activity. Biologically active ACTH was not detected in tumour extracts before incubation with trypsin, but after trypsinization a value of 3.2 mU per gram was obtained. Arterial plasma contained biologically active ACTH (1.5 mU/100 ml) prior to trypsinization. Venous effluent from the thyroid gland contained biologically active (9.6 mU/100 ml) and immunoreactive ACTH (970 pg/ml) before trypsinization. Tumour extracts also contained prolactin production-stimulating activity. These findings can explain the Cushing's syndrome and the galactorrhoea both of which disappeared completely after thyroidectomy."}
{"id": "PMID:184634", "title": "Action of KI, thyroxine and cyclic AMP on [3H]uridine incorporation into the RNA of thyroid slices.", "content": "Potassium iodide (KI) has been shown to impair thyroid protein biosynthesis both in vivo and in vitro. The present study was performed in order to clarify its mechanism of action. Ribonucleic acid (RNA) synthesis was studied in beef thyroid slices with either [32P] or [3H]-uridine as labelled precursors. Both KI and thyroxine (T4) at 10(-5) M significantly decreased RNA labelling under our conditions. In other experiments RNA degradation was examined in pulse-labelled and actinomycin D-treated slices. KI did not modify the degradation of the [3H]-RNA thus indicating that it interferes with the biosynthesis rather than with the degradation of RNA. Taking the perchloric acid soluble radioactivity as a rough index of the precursor pool the present results would indicate an action at this level. Both KC1O4 and methylmercapto-imidazole relieved the gland from the inhibitory action of KI, supporting the view that an intracellular and organified form of iodine is responsible for this action. Since T4 also reproduced the effects of KI on RNA synthesis we would like to propose iodothyronines as the intermediates of this action. Cyclic AMP has been shown to stimulate thyroid protein biosynthesis. The present results demonstrate an action at the RNA level. Cyclic AMP increased both the PCA-soluble and RNA-linked radioactivity, thus suggesting an effect at the RNA precursor pool. KI at 10(-5) M blocked the action of 2 mM cyclic AMP.", "contents": "Action of KI, thyroxine and cyclic AMP on [3H]uridine incorporation into the RNA of thyroid slices. Potassium iodide (KI) has been shown to impair thyroid protein biosynthesis both in vivo and in vitro. The present study was performed in order to clarify its mechanism of action. Ribonucleic acid (RNA) synthesis was studied in beef thyroid slices with either [32P] or [3H]-uridine as labelled precursors. Both KI and thyroxine (T4) at 10(-5) M significantly decreased RNA labelling under our conditions. In other experiments RNA degradation was examined in pulse-labelled and actinomycin D-treated slices. KI did not modify the degradation of the [3H]-RNA thus indicating that it interferes with the biosynthesis rather than with the degradation of RNA. Taking the perchloric acid soluble radioactivity as a rough index of the precursor pool the present results would indicate an action at this level. Both KC1O4 and methylmercapto-imidazole relieved the gland from the inhibitory action of KI, supporting the view that an intracellular and organified form of iodine is responsible for this action. Since T4 also reproduced the effects of KI on RNA synthesis we would like to propose iodothyronines as the intermediates of this action. Cyclic AMP has been shown to stimulate thyroid protein biosynthesis. The present results demonstrate an action at the RNA level. Cyclic AMP increased both the PCA-soluble and RNA-linked radioactivity, thus suggesting an effect at the RNA precursor pool. KI at 10(-5) M blocked the action of 2 mM cyclic AMP."}
{"id": "PMID:184635", "title": "Preliminary observations of bovine adrenal fasciculata-reticularis cells in monolayer culture: steroidogenesis, effect of ACTH and cyclic AMP.", "content": "Bovine adrenocortical cells dispersed by trypsin digestion of fasciculata-reticularis minces were maintained in monolayer culture for up to 6 weeks. During the first week cells grown in medium containing ACTH (1 mU/ml) secreted steroids at a rate 10 to 20-fold greater than control cultures, cortisol accounting for 80-90% of the corticotrophic response. Using tracer amounts of [3H] progesterone and [3H] pregneolone, the major products were cortisol, corticosterone, 11-deoxycortisol and 11-deoxycorticosterone in decreasing order of magnitude. After 10 to 15 days in culture steroidogenesis was no longer enhanced by ACTH. This was concomitant with an apparent loss of 11 beta-hydroxylase activity which was mainly manifested by a sharp increase in the formation of 44-deoxycortisol. Short-term incubations of these cells during the first week in culture provided evidence that steroidogenesis was related to ACTH concentrations (from 0.1 to 100 muU/ml) and stimulated by dibutyryl cyclic AMP, the corticotrophic responses being further enhanced by theophylline (0.5to 50 mumoles/5 ml). Exposure of the cells to ACTH (50 muU/ml) resulted in a rapid increase in intracellular cyclic AMP contractions concomitant with a progressive increase in the corticosteroids released into the medium.", "contents": "Preliminary observations of bovine adrenal fasciculata-reticularis cells in monolayer culture: steroidogenesis, effect of ACTH and cyclic AMP. Bovine adrenocortical cells dispersed by trypsin digestion of fasciculata-reticularis minces were maintained in monolayer culture for up to 6 weeks. During the first week cells grown in medium containing ACTH (1 mU/ml) secreted steroids at a rate 10 to 20-fold greater than control cultures, cortisol accounting for 80-90% of the corticotrophic response. Using tracer amounts of [3H] progesterone and [3H] pregneolone, the major products were cortisol, corticosterone, 11-deoxycortisol and 11-deoxycorticosterone in decreasing order of magnitude. After 10 to 15 days in culture steroidogenesis was no longer enhanced by ACTH. This was concomitant with an apparent loss of 11 beta-hydroxylase activity which was mainly manifested by a sharp increase in the formation of 44-deoxycortisol. Short-term incubations of these cells during the first week in culture provided evidence that steroidogenesis was related to ACTH concentrations (from 0.1 to 100 muU/ml) and stimulated by dibutyryl cyclic AMP, the corticotrophic responses being further enhanced by theophylline (0.5to 50 mumoles/5 ml). Exposure of the cells to ACTH (50 muU/ml) resulted in a rapid increase in intracellular cyclic AMP contractions concomitant with a progressive increase in the corticosteroids released into the medium."}
{"id": "PMID:184636", "title": "Granulocyte function in untreated acute and chronic granulocytic leukemia.", "content": "Untreated patients with acute granulocytic leukemia showed impairment of microbicidal activity and,, in one, this was associated with myeloperoxidase deficiency and staphylococcal infection. In chronic granulocytic leukemia, there was no significant impairment of microbial killing. However, reduction in the capacity to reduce nitro-blue tetrazolium indicated some disturbance of neutrophil function in this disorder.", "contents": "Granulocyte function in untreated acute and chronic granulocytic leukemia. Untreated patients with acute granulocytic leukemia showed impairment of microbicidal activity and,, in one, this was associated with myeloperoxidase deficiency and staphylococcal infection. In chronic granulocytic leukemia, there was no significant impairment of microbial killing. However, reduction in the capacity to reduce nitro-blue tetrazolium indicated some disturbance of neutrophil function in this disorder."}
{"id": "PMID:184637", "title": "Cytoenzymology of benign and malignant tumours of the corpus uteri. I. Respiratory enzymes.", "content": "The activity of a group of respiratory enzymes was studied in normal menopausal as well as benign and malignant tumours. A decrease in the activity of succinic dehydrogenase, diphosphopyridine nucleotide diaphorase and cytochrome oxidase in malignant tumours especially in spindle cell sarcoma and undifferentiated adenocarcinoma was observed. Benign tumours manifested variable results, thus cellular fibromyoma showed no changes in the activity of succinic dehydrogenase, diphosphopyridine nucleotide diaphorase and cytochrome oxidase whereas fibromyomal cells exhibited less enzymatic activity. In addition, no marked difference was observed in the activity of glucose-6-phosphate dehydrogenase in the aforementioned tumours as compared with normal menopausal uterine tissues.", "contents": "Cytoenzymology of benign and malignant tumours of the corpus uteri. I. Respiratory enzymes. The activity of a group of respiratory enzymes was studied in normal menopausal as well as benign and malignant tumours. A decrease in the activity of succinic dehydrogenase, diphosphopyridine nucleotide diaphorase and cytochrome oxidase in malignant tumours especially in spindle cell sarcoma and undifferentiated adenocarcinoma was observed. Benign tumours manifested variable results, thus cellular fibromyoma showed no changes in the activity of succinic dehydrogenase, diphosphopyridine nucleotide diaphorase and cytochrome oxidase whereas fibromyomal cells exhibited less enzymatic activity. In addition, no marked difference was observed in the activity of glucose-6-phosphate dehydrogenase in the aforementioned tumours as compared with normal menopausal uterine tissues."}
{"id": "PMID:184638", "title": "The reactions of rabbit gall bladder epithelium to electron microscopic stainings for carbohydrates with 1,2-glycol groupings.", "content": "In the rabbit gall bladder epithelium several ultrastructural elements have been reacted positively for different electron microscopic stainings for carbohydrates with 1,2-glycol groupings. These elements include the surface coat of the plasma membrane, pinocytotic vesicles, certain elements of the Golgi apparatus, secretory granules, lysosome-like bodies and glycogen particles. These ultrastructural elements were found to vary in reactivity with different staining procedures for the demonstration of the carbohydrates. Attempts were made to correlate the positive reactions of some of these carbohydrate-containing elements with their cytophysiological functions, and the varying reactivity of the carbohydrate-containing elements with different staining methods was discussed in relation to factors involved in the staining reactions concerned.", "contents": "The reactions of rabbit gall bladder epithelium to electron microscopic stainings for carbohydrates with 1,2-glycol groupings. In the rabbit gall bladder epithelium several ultrastructural elements have been reacted positively for different electron microscopic stainings for carbohydrates with 1,2-glycol groupings. These elements include the surface coat of the plasma membrane, pinocytotic vesicles, certain elements of the Golgi apparatus, secretory granules, lysosome-like bodies and glycogen particles. These ultrastructural elements were found to vary in reactivity with different staining procedures for the demonstration of the carbohydrates. Attempts were made to correlate the positive reactions of some of these carbohydrate-containing elements with their cytophysiological functions, and the varying reactivity of the carbohydrate-containing elements with different staining methods was discussed in relation to factors involved in the staining reactions concerned."}
{"id": "PMID:184639", "title": "Ultrastructural study of the adenohypophysis of the Chinese hamster.", "content": "The adenohypophysis of normal Chinese hamsters of both sexes was examined ultrastructurally. Organs were fixed by intravascular perfusion with S-collidine-buffered glutaraldehyde solution. Seven types of cells were differentiated and, according to morphological characteristics, classified as (1) mammotropes, with very large (400-800 nm) polymorphous secretory granules; (2) somatotropes, either in the storage phase with numerous large, dense granules (average 300 nm), or in the hormone synthesis phase, with abundant endoplasmic reticulum and large Golgi apparatus; (3) corticotropes, with irregular cell shape, and granules (average 160 nm) arranged in lines parallel to the cell membrane; (4) FSH gonadotropes, with abundant and dilated endoplasmic reticulum, and granules (190-320 nm) uniformly distributed in the cytoplasm; (5) LH gonadotropes, with granules (120-220 nm) of varied density; (6) thyrotropes, with irregular cell shape and very small granules (120-160 nm), and (7) agranulated cells. The ultrastructure of the adenohypophysis of the Chinese hamster corresponds closely with observations reported in rats, mice and Syrian hamsters.", "contents": "Ultrastructural study of the adenohypophysis of the Chinese hamster. The adenohypophysis of normal Chinese hamsters of both sexes was examined ultrastructurally. Organs were fixed by intravascular perfusion with S-collidine-buffered glutaraldehyde solution. Seven types of cells were differentiated and, according to morphological characteristics, classified as (1) mammotropes, with very large (400-800 nm) polymorphous secretory granules; (2) somatotropes, either in the storage phase with numerous large, dense granules (average 300 nm), or in the hormone synthesis phase, with abundant endoplasmic reticulum and large Golgi apparatus; (3) corticotropes, with irregular cell shape, and granules (average 160 nm) arranged in lines parallel to the cell membrane; (4) FSH gonadotropes, with abundant and dilated endoplasmic reticulum, and granules (190-320 nm) uniformly distributed in the cytoplasm; (5) LH gonadotropes, with granules (120-220 nm) of varied density; (6) thyrotropes, with irregular cell shape and very small granules (120-160 nm), and (7) agranulated cells. The ultrastructure of the adenohypophysis of the Chinese hamster corresponds closely with observations reported in rats, mice and Syrian hamsters."}
{"id": "PMID:184641", "title": "Medulloblastomas and other neural tumours in mice treated neonatally with N-ethyl-N-nitrosourea.", "content": "Newborn mice of four inbred strains were injected with a single dose of N-ethyl-N-nitrosourea. The wide range of tumours induced included a small number in the central and peripheral nervous systems. The 4 brain tumours all arose in the cerebellum. Three in one strain were medulloblastomas showing continuity with the internal granular layer. All three tumours showed diffuse infiltration through the molecular layer and continuity with densely-packed islets of cells that marginated immediately beneath the pia and closely resembled remnants of a persistent fetal external granular layer. The medulloblastomas are discussed with special relevance to the histogenesis of the equivalent tumour in man.", "contents": "Medulloblastomas and other neural tumours in mice treated neonatally with N-ethyl-N-nitrosourea. Newborn mice of four inbred strains were injected with a single dose of N-ethyl-N-nitrosourea. The wide range of tumours induced included a small number in the central and peripheral nervous systems. The 4 brain tumours all arose in the cerebellum. Three in one strain were medulloblastomas showing continuity with the internal granular layer. All three tumours showed diffuse infiltration through the molecular layer and continuity with densely-packed islets of cells that marginated immediately beneath the pia and closely resembled remnants of a persistent fetal external granular layer. The medulloblastomas are discussed with special relevance to the histogenesis of the equivalent tumour in man."}
{"id": "PMID:184642", "title": "Infantile neuroaxonal dystrophy. Ultrastructural study of peripheral nerve.", "content": "Ultrastructural study of the biopsied sural nerve in a case of infantile neuroaxonal dystrophy was made. The characteristic change in the ballooned axons is an accumulation of membranous profiles associated with mitochondria, glycogen like granules, dense bodies, vesicles and electron lucent material. The membranous profile is classified into three morphological types and discussed on each of them. Probably tubulomembranous profile of the first type is most common and may be cardinal deposit in this condition. These membranous structures of various types might be, however, only different manifestations occurring on the same morbid process. Enormous amount of glycogen like granules and mitochondria might be related to the metabolic derangement of carbohydrate in the ballooned axons. Electron lucent material we observed was not described in the previous papers on this condition. We added one more example showing that nerve biopsy is helpful to confirm the diagnosis in infantile neuroaxonal dystrophy.", "contents": "Infantile neuroaxonal dystrophy. Ultrastructural study of peripheral nerve. Ultrastructural study of the biopsied sural nerve in a case of infantile neuroaxonal dystrophy was made. The characteristic change in the ballooned axons is an accumulation of membranous profiles associated with mitochondria, glycogen like granules, dense bodies, vesicles and electron lucent material. The membranous profile is classified into three morphological types and discussed on each of them. Probably tubulomembranous profile of the first type is most common and may be cardinal deposit in this condition. These membranous structures of various types might be, however, only different manifestations occurring on the same morbid process. Enormous amount of glycogen like granules and mitochondria might be related to the metabolic derangement of carbohydrate in the ballooned axons. Electron lucent material we observed was not described in the previous papers on this condition. We added one more example showing that nerve biopsy is helpful to confirm the diagnosis in infantile neuroaxonal dystrophy."}
{"id": "PMID:184643", "title": "Dense core mitochondria in peripheral ganglia of man.", "content": "Neuronal perikarye of peripheral ganglia contained unusual dense core mitochondria that were not seen in other cell types or tissues of the same individual. They were found in several patients autopsied with GM1-gangliosidosis and neuronal ceroid-lipofuscinosis. Previous observations on human sympathetic ganglia, obtained by biopsy, and our findings suggest that these dense core mitochondria might represent a rare but regular feature of neuronal perikarya in peripheral ganglia of man.", "contents": "Dense core mitochondria in peripheral ganglia of man. Neuronal perikarye of peripheral ganglia contained unusual dense core mitochondria that were not seen in other cell types or tissues of the same individual. They were found in several patients autopsied with GM1-gangliosidosis and neuronal ceroid-lipofuscinosis. Previous observations on human sympathetic ganglia, obtained by biopsy, and our findings suggest that these dense core mitochondria might represent a rare but regular feature of neuronal perikarya in peripheral ganglia of man."}
{"id": "PMID:184644", "title": "Effects of topical glucocorticoid medication on collagen biosynthesis in the dental pulp.", "content": "The aim of the study was to observe pulpal collagen synthesis in response to trauma and to glucocorticoid medication. The material consisted of 290 rabbit pulps and 76 human premolar pulps. Collagen synthesis was determined by incubating whole pulps in a medium containing [14C]proline, and measuring the formation of [14C]hydroxyproline. The effect of glucocorticoids was studied in vitro using rabbit pulps. Hydrocortisone and dexamethasone inhibited collagen synthesis, whereas prednisolone had no marked effect. Hydrocortisone was found to inhibit the synthesis of [14C]hydroxyproline in neutral salt soluble and insoluble non-dialyzable collagen fractions. [14C]hydroxyproline in the dialyzable fraction was increased, suggesting that hydrocortisone increased collagen degradation. In the human material, premolar pulps were experimentally exposed and then medicated with capping agents. The contralateral teeth were exposed and capped with other capping materials, in some cases they were left as intact controls. The exposure led to an increase in the collagen synthesis as indicated by increased [14C]hydroxyproline formation and elevated protocollagen proline hydroxylase activity in the pulp. This enzyme activity was suppressed in pulps capped with a glucocorticoid paste. In addition, the collagen synthesis rate was lower in pulps treated with another glucocorticoid containing compound, when compared to pulps capped with a calcium hydroxide preparation.", "contents": "Effects of topical glucocorticoid medication on collagen biosynthesis in the dental pulp. The aim of the study was to observe pulpal collagen synthesis in response to trauma and to glucocorticoid medication. The material consisted of 290 rabbit pulps and 76 human premolar pulps. Collagen synthesis was determined by incubating whole pulps in a medium containing [14C]proline, and measuring the formation of [14C]hydroxyproline. The effect of glucocorticoids was studied in vitro using rabbit pulps. Hydrocortisone and dexamethasone inhibited collagen synthesis, whereas prednisolone had no marked effect. Hydrocortisone was found to inhibit the synthesis of [14C]hydroxyproline in neutral salt soluble and insoluble non-dialyzable collagen fractions. [14C]hydroxyproline in the dialyzable fraction was increased, suggesting that hydrocortisone increased collagen degradation. In the human material, premolar pulps were experimentally exposed and then medicated with capping agents. The contralateral teeth were exposed and capped with other capping materials, in some cases they were left as intact controls. The exposure led to an increase in the collagen synthesis as indicated by increased [14C]hydroxyproline formation and elevated protocollagen proline hydroxylase activity in the pulp. This enzyme activity was suppressed in pulps capped with a glucocorticoid paste. In addition, the collagen synthesis rate was lower in pulps treated with another glucocorticoid containing compound, when compared to pulps capped with a calcium hydroxide preparation."}
{"id": "PMID:184640", "title": "[ACTH therapy and peritumoral oedema (author's transl)].", "content": "Out of the various drugs which may be used in the treatment of intracramial hypertension we have tested long-acting Synacthen (Synacthen-d\u00e9pot) in patients with inoperable cerebral tumours. The results were favourable, especially in the case of long-term treatment, since the delayed action of the drug allows flexible application while ensuring significant comfort for the patient.", "contents": "[ACTH therapy and peritumoral oedema (author's transl)]. Out of the various drugs which may be used in the treatment of intracramial hypertension we have tested long-acting Synacthen (Synacthen-d\u00e9pot) in patients with inoperable cerebral tumours. The results were favourable, especially in the case of long-term treatment, since the delayed action of the drug allows flexible application while ensuring significant comfort for the patient."}
{"id": "PMID:184682", "title": "Human interferon and cell growth inhibition. I. Inhibitory effect of human interferon on the growth rate of cultured human cells.", "content": "Human interferon inhibited the growth rate of cultured human cells. These included diploid fibroblast cells from embryonal lung and skin, established lines of HeLa and U-amnion cells, all grown in monolayer; and the established lymphoblastoid line P3HR1 grown in suspension. Cells growing fast were inhibited to a higher degree than those growing slowly. The inhibitory effect was dose dependent but the dose-dependency was different in various cell types. The inhibitory effect of leukocyte interferon and fibroblast interferon was quantitatively comparable.", "contents": "Human interferon and cell growth inhibition. I. Inhibitory effect of human interferon on the growth rate of cultured human cells. Human interferon inhibited the growth rate of cultured human cells. These included diploid fibroblast cells from embryonal lung and skin, established lines of HeLa and U-amnion cells, all grown in monolayer; and the established lymphoblastoid line P3HR1 grown in suspension. Cells growing fast were inhibited to a higher degree than those growing slowly. The inhibitory effect was dose dependent but the dose-dependency was different in various cell types. The inhibitory effect of leukocyte interferon and fibroblast interferon was quantitatively comparable."}
{"id": "PMID:184683", "title": "Effects of secretagogues on oxygen consumption, aminopyrine accumulation and morphology in isolated gastric glands.", "content": "A recently developed method to isolate gastric glands from the rabbit gastric mucosa (Berglindh and Obrink 1976) was used to study the effects of some common gastric secretagogues. Three parameters were investigated: 1) Respiratory activity; 2) Intraglandular accumulation of the weak base aminopyrine; 3) Quantitative morphology of the parietal cells. The following substances were tested: Histamine, cAMP, db-cAMP, aminophylline, carbachol and pentagastrin. The strongest effect was obtained with db-cAMP which dose-dependently stimulated the respiration up to 200%, increased the aminopyrine accumulation 80% and altered the parietal cell morphology from a typically resting to a typically stimulated state. cAMP also stimulated the respiration but was about 10 times less effective on a molar basis than the dibutyryl form. Histamine, like db-cAMP, stimulated the respiration in a dose-dependent manner and strongly increased the aminopyrine accumulation. The morphological changes were, however, not of the same magnitude as after db-cAMP. Aminophylline, tested only for respiratory activity, stimulated the oxygen consumpation moderately. Carbachol induced a transient increase in both the oxygen consumption and in the aminopyrine accumulation with a peak value after approximately 15 minutes for both, but gave no significant morphological alterations. Pentagastrin, finally, was incapable of inducing changes in any of the three parameters. Aminopyrine was also found to accumulate approx. 50 times in unstimulated, morphologically resting glands. This seems to indicate that there might be acid sites already in resting glands.", "contents": "Effects of secretagogues on oxygen consumption, aminopyrine accumulation and morphology in isolated gastric glands. A recently developed method to isolate gastric glands from the rabbit gastric mucosa (Berglindh and Obrink 1976) was used to study the effects of some common gastric secretagogues. Three parameters were investigated: 1) Respiratory activity; 2) Intraglandular accumulation of the weak base aminopyrine; 3) Quantitative morphology of the parietal cells. The following substances were tested: Histamine, cAMP, db-cAMP, aminophylline, carbachol and pentagastrin. The strongest effect was obtained with db-cAMP which dose-dependently stimulated the respiration up to 200%, increased the aminopyrine accumulation 80% and altered the parietal cell morphology from a typically resting to a typically stimulated state. cAMP also stimulated the respiration but was about 10 times less effective on a molar basis than the dibutyryl form. Histamine, like db-cAMP, stimulated the respiration in a dose-dependent manner and strongly increased the aminopyrine accumulation. The morphological changes were, however, not of the same magnitude as after db-cAMP. Aminophylline, tested only for respiratory activity, stimulated the oxygen consumpation moderately. Carbachol induced a transient increase in both the oxygen consumption and in the aminopyrine accumulation with a peak value after approximately 15 minutes for both, but gave no significant morphological alterations. Pentagastrin, finally, was incapable of inducing changes in any of the three parameters. Aminopyrine was also found to accumulate approx. 50 times in unstimulated, morphologically resting glands. This seems to indicate that there might be acid sites already in resting glands."}
{"id": "PMID:184684", "title": "Effect of glucagon on cyclic AMP, albumin metabolism and incorporation of 14C-leucine into proteins in isolated parenchymal rat liver cells.", "content": "Parenchymal rat liver cells were isolated by the collagenase method and incubated in Krebs-Henseleit buffer containing 0.5% gelatin. The basal level of cyclic AMP in isolated cells was 0.52 nmol per g liver wet wt. Glucagon (10(-10)-10(-6) M) caused a significant increase in the level of cyclic AMP. Maximum levels were obtained 2-15 min after addition of glucagon. Repeated administration of glucagon caused a new increase in cyclic AMP, but the response was lesser than after the first addition of glucagon, indicating refractoriness to glucagon. The rate of albumin secretion was 4.6 mug/min per g liver wet wt. This is about the rate found in the perfused liver, Glucagon (10(-8-10(-6) M) inhibited albumin secretion and the incorporation of 14C-leucine into albumin, into total proteins in the medium and into total proteins in the cell suspension. The effect of glucagon on albumin secretion is compatible with an effect on the rate of synthesis. A positive correlation existed between the maximal level of cyclic AMP after glucagon administration and the inhibition of both albumin secretion and the incorporation of 149leucine.", "contents": "Effect of glucagon on cyclic AMP, albumin metabolism and incorporation of 14C-leucine into proteins in isolated parenchymal rat liver cells. Parenchymal rat liver cells were isolated by the collagenase method and incubated in Krebs-Henseleit buffer containing 0.5% gelatin. The basal level of cyclic AMP in isolated cells was 0.52 nmol per g liver wet wt. Glucagon (10(-10)-10(-6) M) caused a significant increase in the level of cyclic AMP. Maximum levels were obtained 2-15 min after addition of glucagon. Repeated administration of glucagon caused a new increase in cyclic AMP, but the response was lesser than after the first addition of glucagon, indicating refractoriness to glucagon. The rate of albumin secretion was 4.6 mug/min per g liver wet wt. This is about the rate found in the perfused liver, Glucagon (10(-8-10(-6) M) inhibited albumin secretion and the incorporation of 14C-leucine into albumin, into total proteins in the medium and into total proteins in the cell suspension. The effect of glucagon on albumin secretion is compatible with an effect on the rate of synthesis. A positive correlation existed between the maximal level of cyclic AMP after glucagon administration and the inhibition of both albumin secretion and the incorporation of 149leucine."}
{"id": "PMID:184685", "title": "Effect of adrenaline on the release of cyclic AMP by the rat diaphragm.", "content": "An investigation was made of the effect of adrenaline on the tissue level and release of cyclic AMP (cAMP) into the incubation medium by the isolated rat diaphragm preparation. Adrenaline, added in vitro, caused a dose-dependent biphasic increase in the tissue level of the nucleotide. A significant elevation of the level of cAMP in the tissue was observed throughout a 60 min incubation period in the presence of 0.01, 0.1 and 10 mug/ml of adrenaline. The hormone also produced a small but significant increase in the release of cAMP into the incubation medium. The accumulation of cAMP in the incubation medium ceased after 10 min of incubation in the presence of adrenaline, although the tissu e level of the nucleotide remained considerably elevated throughout the entire incubation period. Theophylline potentiated the effect of adrenaline on both the accumulation of cAMP in the tissue and in the incubation medium. Theophylline by itself also increased the tissue level of cAMP slightly. It is concluded from the present study that the elimination of cAMP from the rat diaphragm muscle by release of the nucleotide from the cells is small.", "contents": "Effect of adrenaline on the release of cyclic AMP by the rat diaphragm. An investigation was made of the effect of adrenaline on the tissue level and release of cyclic AMP (cAMP) into the incubation medium by the isolated rat diaphragm preparation. Adrenaline, added in vitro, caused a dose-dependent biphasic increase in the tissue level of the nucleotide. A significant elevation of the level of cAMP in the tissue was observed throughout a 60 min incubation period in the presence of 0.01, 0.1 and 10 mug/ml of adrenaline. The hormone also produced a small but significant increase in the release of cAMP into the incubation medium. The accumulation of cAMP in the incubation medium ceased after 10 min of incubation in the presence of adrenaline, although the tissu e level of the nucleotide remained considerably elevated throughout the entire incubation period. Theophylline potentiated the effect of adrenaline on both the accumulation of cAMP in the tissue and in the incubation medium. Theophylline by itself also increased the tissue level of cAMP slightly. It is concluded from the present study that the elimination of cAMP from the rat diaphragm muscle by release of the nucleotide from the cells is small."}
{"id": "PMID:184686", "title": "Treatment of metastases in nephroblastoma.", "content": "A series of 36 children with nephroblastoma treated between 1966 and 1973 was analysed. None of the patients with stages I or II and microscopic type I or II developed metastases; 5 of 7 patients with stages I or II and microscopic type III developed metastases. All patients in stage III developed metastases. Fifteen patients developed metastases after the termination of the primary treatment. Of 9 patients with pulmonary metastases only, 6 are free of disease, all patients with metastases in other sites are dead.", "contents": "Treatment of metastases in nephroblastoma. A series of 36 children with nephroblastoma treated between 1966 and 1973 was analysed. None of the patients with stages I or II and microscopic type I or II developed metastases; 5 of 7 patients with stages I or II and microscopic type III developed metastases. All patients in stage III developed metastases. Fifteen patients developed metastases after the termination of the primary treatment. Of 9 patients with pulmonary metastases only, 6 are free of disease, all patients with metastases in other sites are dead."}
{"id": "PMID:184687", "title": "Macrophage migration inhibition-activity after implantation of methylcholanthrene-induced sarcoma, Ehrlich ascites cancer or mouse ascites hepatoma-134 cancer cells in mice.", "content": "Cells from methylcholanthrene-induced tumor (MC-tumor), Ehrlich ascites cancer or mouse ascites hepatoma (MH-134) were subcutaneously implanted in dorsal area of mice to examine the specific cell mediated immunity following implantation. The migration index (MI) of lymphocytes was determined at various time periods after cell transplantation. The MI-activity increased under all three implantations, reached maximum at a certain period, decreased gradually and disappeared. The maximum MI-activity coincided with the proliferation period of the implanted tumor cells. This peak occurred on the tenth postimplantation day with MC-tumors, on the fifth day with Ehrlich ascites cancer and on the sixth day with MH-134 cancer. In lymphoid tissues of animals with MC-tumor and Ehrlich ascites cancer, strong MI-activity appeared early in the regional axillary lymph nodes, while weak activity was observed consistently in the distant mesenterial lymph nodes. The MI-activity of the splenic lymphoid cells resembled the axillary lymph nodes cell activity. The MI-activity of venous blood lymphoid cells was parallel to the average value of lymphoid cells of the spleen and axillary and mesenterial lymph nodes.", "contents": "Macrophage migration inhibition-activity after implantation of methylcholanthrene-induced sarcoma, Ehrlich ascites cancer or mouse ascites hepatoma-134 cancer cells in mice. Cells from methylcholanthrene-induced tumor (MC-tumor), Ehrlich ascites cancer or mouse ascites hepatoma (MH-134) were subcutaneously implanted in dorsal area of mice to examine the specific cell mediated immunity following implantation. The migration index (MI) of lymphocytes was determined at various time periods after cell transplantation. The MI-activity increased under all three implantations, reached maximum at a certain period, decreased gradually and disappeared. The maximum MI-activity coincided with the proliferation period of the implanted tumor cells. This peak occurred on the tenth postimplantation day with MC-tumors, on the fifth day with Ehrlich ascites cancer and on the sixth day with MH-134 cancer. In lymphoid tissues of animals with MC-tumor and Ehrlich ascites cancer, strong MI-activity appeared early in the regional axillary lymph nodes, while weak activity was observed consistently in the distant mesenterial lymph nodes. The MI-activity of the splenic lymphoid cells resembled the axillary lymph nodes cell activity. The MI-activity of venous blood lymphoid cells was parallel to the average value of lymphoid cells of the spleen and axillary and mesenterial lymph nodes."}
{"id": "PMID:184688", "title": "Immunoreactive insulin in portal and hepatic venous blood in patients with insuloma.", "content": "The insulin level has been determined simultaneously in portal and hepatic venous blood in four patients with insuloma before and after administration of glucose and tolbutamide. Three patients displayed a higher insulin level in hepatic than in portal blood, although no hepatic metastases could be detected by radiologic examination. In contrast, portal insulin concentrations always exceeded hepatic in four control patients investigated in a similar way. The implications of these results are discussed.", "contents": "Immunoreactive insulin in portal and hepatic venous blood in patients with insuloma. The insulin level has been determined simultaneously in portal and hepatic venous blood in four patients with insuloma before and after administration of glucose and tolbutamide. Three patients displayed a higher insulin level in hepatic than in portal blood, although no hepatic metastases could be detected by radiologic examination. In contrast, portal insulin concentrations always exceeded hepatic in four control patients investigated in a similar way. The implications of these results are discussed."}
{"id": "PMID:184689", "title": "Relationship between intracellular cyclic AMP and lipolysis in human adipose tissue.", "content": "Human subcutaneous adipose tissue has been incubated in vitro in the presence and absence of isoprenaline (ISNA). The tissue concentration of cyclic AMP (cAMP) and the release of glycerol into the incubation medium were measured after various incubation periods. In the presence of ISNA (6 X 10(-5) mol/l), the tissue concentration of cAMP reached a peak after around 10 min and then declined to a level significantly lower than that at the start of the incubation. In contrast, the ISNA-induced rate of lipolysis was a linear function of the incubation time. The addition of propranolol (13 mumol/l) at different times after ISNA did not influence the rate of lipolysis, although it resulted in a decrease in the tissue level of cAMP. There was a positive correlation between the maximal increase in tissue cAMP and the rate of lipolysis in adipose tissue exposed to ISNA, both in individual experiments and in a group of 23 persons. No correlation was found between the rate of lipolysis and the tissue level of cAMP in adipose tissue incubated under basal conditions. The findings are compatible with the theory that the beta-adrenergic-induced lipolysis by human adipose tissue is a function of the maximal rise in the concentration of tissue cAMP. It is concluded that this peak level of cAMP represents single compartment of the nucleotide.", "contents": "Relationship between intracellular cyclic AMP and lipolysis in human adipose tissue. Human subcutaneous adipose tissue has been incubated in vitro in the presence and absence of isoprenaline (ISNA). The tissue concentration of cyclic AMP (cAMP) and the release of glycerol into the incubation medium were measured after various incubation periods. In the presence of ISNA (6 X 10(-5) mol/l), the tissue concentration of cAMP reached a peak after around 10 min and then declined to a level significantly lower than that at the start of the incubation. In contrast, the ISNA-induced rate of lipolysis was a linear function of the incubation time. The addition of propranolol (13 mumol/l) at different times after ISNA did not influence the rate of lipolysis, although it resulted in a decrease in the tissue level of cAMP. There was a positive correlation between the maximal increase in tissue cAMP and the rate of lipolysis in adipose tissue exposed to ISNA, both in individual experiments and in a group of 23 persons. No correlation was found between the rate of lipolysis and the tissue level of cAMP in adipose tissue incubated under basal conditions. The findings are compatible with the theory that the beta-adrenergic-induced lipolysis by human adipose tissue is a function of the maximal rise in the concentration of tissue cAMP. It is concluded that this peak level of cAMP represents single compartment of the nucleotide."}
{"id": "PMID:184690", "title": "Metabolism of mono- and diacylglycerols in subcutaneous adipose tissue of obese and normal-weight subjects.", "content": "Tissue monoacylglycerols (MG), diacylglycerols (DG), free fatty acids (FFA), and cyclic AMP (cAMP) and release of FFA and glycerol have been studied in vitro in subcutaneous adipose tissue of 6 obese and 7 normal-weight subjects. The tissue was incubated without or with 6 X 10(-5) mol/l of isoprenaline (ISNA). The DG level and the fat cell volume were strongly interrelated (r=+0.95,  p less than 0.001). The concentration of DG was increased (p less than 0.05) in obesity. The changes in DG and MG were significantly interrelated (r=+0.65, p less than 0.05) during basal incubation. ISNA increased the DG concentration in a way that was correlated (r=+0.81, p less than 0.001) with the ISNA-induced glycerol release. This indicates that 1) the basal metabolic activities of MG and DG lipase are similar and 2) DG lipase is an important rate limiting factor in lipolysis. Without ISNA, tissue FFA and the release of FFA and glycerol were significantly increased in the obese patients. As a mean, MG and DG did not accumulate in the basal state in the two patient groups. The findings indicate that basal lipolysis was increased in obesity. This was probably due to increased basal metabolic activity of triacylglycerol lipase, since the basal cAMP levels were similar in the two patient groups. In the presence of ISNA, the production of FFA and the glycerol release were similar in both patient groups, as was the increase in tissue DG. Also the ISNA-induced maximal level of cAMP was similar in the two groups. With ISNA, a small increment of MG was observed in adipose tissue of the normal-weight subjects. Taking all metabolites into account, the rate of lipolysis as well as the activation of triacylglycerol lipase via cAMP in the presence of ISNA appeared to be unaltered in obesity. Separate experiments with 1-14C-glycerol provided further evidence for the existence of a MG pathway for the esterification of FFA.", "contents": "Metabolism of mono- and diacylglycerols in subcutaneous adipose tissue of obese and normal-weight subjects. Tissue monoacylglycerols (MG), diacylglycerols (DG), free fatty acids (FFA), and cyclic AMP (cAMP) and release of FFA and glycerol have been studied in vitro in subcutaneous adipose tissue of 6 obese and 7 normal-weight subjects. The tissue was incubated without or with 6 X 10(-5) mol/l of isoprenaline (ISNA). The DG level and the fat cell volume were strongly interrelated (r=+0.95,  p less than 0.001). The concentration of DG was increased (p less than 0.05) in obesity. The changes in DG and MG were significantly interrelated (r=+0.65, p less than 0.05) during basal incubation. ISNA increased the DG concentration in a way that was correlated (r=+0.81, p less than 0.001) with the ISNA-induced glycerol release. This indicates that 1) the basal metabolic activities of MG and DG lipase are similar and 2) DG lipase is an important rate limiting factor in lipolysis. Without ISNA, tissue FFA and the release of FFA and glycerol were significantly increased in the obese patients. As a mean, MG and DG did not accumulate in the basal state in the two patient groups. The findings indicate that basal lipolysis was increased in obesity. This was probably due to increased basal metabolic activity of triacylglycerol lipase, since the basal cAMP levels were similar in the two patient groups. In the presence of ISNA, the production of FFA and the glycerol release were similar in both patient groups, as was the increase in tissue DG. Also the ISNA-induced maximal level of cAMP was similar in the two groups. With ISNA, a small increment of MG was observed in adipose tissue of the normal-weight subjects. Taking all metabolites into account, the rate of lipolysis as well as the activation of triacylglycerol lipase via cAMP in the presence of ISNA appeared to be unaltered in obesity. Separate experiments with 1-14C-glycerol provided further evidence for the existence of a MG pathway for the esterification of FFA."}
{"id": "PMID:184691", "title": "Urinary cyclic AMP. Relation to albumin-corrected serum calcium in healthy persons and patients with primary hyperparathyroidism.", "content": "In 21 healthy volunteers, mean excretion of cyclic adenosine 3',5' monophosphate (cAMP) in urine was 4.2 +/- 1.0 (S.D.) mumol cAMP/24 hours, 3.0 +/- 1.2 mumol/g creatinine and 3.8 +/- 1.2 mumol/24 hours/100 ml/min renal clearance of creatinine (CCr). An inverse correlation exists between the excretion of cAMP and serum calcium corrected for variations in serum albumin, most clearly demonstrated when cAMP is expressed as mumol/24 hours/100 ml/min of CCr (r=-0.630, p less than 0.01). In 21 patients with operatively verified hyperparathyroidism, the mean urinary excretion of cAMP/24 hours was 5.0 +/- 1.9 mumol uncorrected, 4.8 +/- 1.8 mumol/g creatinine and 6.6 +/- 2.1 mumol/100 ml/min of CCr. The latter two of these parameters differ significantly from the normal group (p less than 0.001), but conceal the fact that many patients with hyperparathyroidism excrete normal amounts of cAMP in the urine, independent of the mode of calculation. However, when cAMP is correlated to albumin-corrected serum calcium, this overlap between hyperparathyroidism and normality disappears completely. The results support the concept that cAMP excretion is influenced to a considerable degree by the biological activity of circulating parathyroid hormone. They also indicate that the simultaneous measurement of cAMP in urine and albumin-corrected calcium in serum is a useful aid in distinguishing hyperparathyroidism from the state of normality.", "contents": "Urinary cyclic AMP. Relation to albumin-corrected serum calcium in healthy persons and patients with primary hyperparathyroidism. In 21 healthy volunteers, mean excretion of cyclic adenosine 3',5' monophosphate (cAMP) in urine was 4.2 +/- 1.0 (S.D.) mumol cAMP/24 hours, 3.0 +/- 1.2 mumol/g creatinine and 3.8 +/- 1.2 mumol/24 hours/100 ml/min renal clearance of creatinine (CCr). An inverse correlation exists between the excretion of cAMP and serum calcium corrected for variations in serum albumin, most clearly demonstrated when cAMP is expressed as mumol/24 hours/100 ml/min of CCr (r=-0.630, p less than 0.01). In 21 patients with operatively verified hyperparathyroidism, the mean urinary excretion of cAMP/24 hours was 5.0 +/- 1.9 mumol uncorrected, 4.8 +/- 1.8 mumol/g creatinine and 6.6 +/- 2.1 mumol/100 ml/min of CCr. The latter two of these parameters differ significantly from the normal group (p less than 0.001), but conceal the fact that many patients with hyperparathyroidism excrete normal amounts of cAMP in the urine, independent of the mode of calculation. However, when cAMP is correlated to albumin-corrected serum calcium, this overlap between hyperparathyroidism and normality disappears completely. The results support the concept that cAMP excretion is influenced to a considerable degree by the biological activity of circulating parathyroid hormone. They also indicate that the simultaneous measurement of cAMP in urine and albumin-corrected calcium in serum is a useful aid in distinguishing hyperparathyroidism from the state of normality."}
{"id": "PMID:184692", "title": "Allosteric enzyme-tRNA complexes as regulators of transcription or translation.", "content": "The dehydrogenase activity of chorismate mutase-prephenate dehydrogenase, the allosteric enzyme of the tyrosine biosynthetic pathway in Escherichia coli, is inhibited by tRNA. The inhibitory effect of tRNA from E. coli is specific, other RNA species or polynucleotides have no inhibitory effect or only slightly influence the activity of the enzyme. While NAD only slightly influences the inhibitory effect of tRNA from E. coli, prephenic acid at high concentrations suppresses the inhibition. In he presence of a fixed concentration of NAD and low concentration or absence of prephenic acid the inhibitory effect of tRNA is time and temperature dependent. It seems that in the presence of tRNA and low concentration of prephenate the enzyme undergoes a time and temperature dependent conformational change. This process is reversible and can be influenced by the concentration of prephenic acid, the first precursor of the tyrosine biosynthetic pathway. The possible regulatory role of allosteric enzyme-tRNA complexes is discussed.", "contents": "Allosteric enzyme-tRNA complexes as regulators of transcription or translation. The dehydrogenase activity of chorismate mutase-prephenate dehydrogenase, the allosteric enzyme of the tyrosine biosynthetic pathway in Escherichia coli, is inhibited by tRNA. The inhibitory effect of tRNA from E. coli is specific, other RNA species or polynucleotides have no inhibitory effect or only slightly influence the activity of the enzyme. While NAD only slightly influences the inhibitory effect of tRNA from E. coli, prephenic acid at high concentrations suppresses the inhibition. In he presence of a fixed concentration of NAD and low concentration or absence of prephenic acid the inhibitory effect of tRNA is time and temperature dependent. It seems that in the presence of tRNA and low concentration of prephenate the enzyme undergoes a time and temperature dependent conformational change. This process is reversible and can be influenced by the concentration of prephenic acid, the first precursor of the tyrosine biosynthetic pathway. The possible regulatory role of allosteric enzyme-tRNA complexes is discussed."}
{"id": "PMID:184702", "title": "Haemorrhagic and inflammatory properties of collagenase from C. histolyticum.", "content": "Collagenase from Clostridium histolyticum induced haemorrhages when applied to the surface of dog lung; it exerted a similar effect on mouse lung when injected intrathoracically. Injected into rat paws, bacterial collagenase induced haemorrhage and oedema. Effects of collagenase were prevented by several procedures that inhibit collagenolytic activity (heating at various temperatures and incubation with metal-complexing agents such as EDTA, penicillamine and dithiothreitol). Protein protease inhibitors, dexamethasone and standard acidic anti-inflammatory drugs had only a slight or no effect on collagenase-induced haemorrhages; dexamethasone and acidic anti-inflammatory drugs blocked collagenase-induced oedema. Inhibition of endogenous kinin-releasing mechanisms by administration of hexadimethrine, a recognized inhibitor of the activation of clotting Factor XII, and depletion of kininogen by administration of carrageenin blocked collagenase-induced oedema. Collagenase did not increase permeability of rat skin vessels, nor did it release potential inflammatory mediators, such as bradykinin or prostaglandins, from plasma or platelets. Bacterial collagenase-induced haemorrhage presumably resulted from enzymatic destruction of membranous structures; at least a portion of the inflammatory response may be due to activation of a kinin-like system.", "contents": "Haemorrhagic and inflammatory properties of collagenase from C. histolyticum. Collagenase from Clostridium histolyticum induced haemorrhages when applied to the surface of dog lung; it exerted a similar effect on mouse lung when injected intrathoracically. Injected into rat paws, bacterial collagenase induced haemorrhage and oedema. Effects of collagenase were prevented by several procedures that inhibit collagenolytic activity (heating at various temperatures and incubation with metal-complexing agents such as EDTA, penicillamine and dithiothreitol). Protein protease inhibitors, dexamethasone and standard acidic anti-inflammatory drugs had only a slight or no effect on collagenase-induced haemorrhages; dexamethasone and acidic anti-inflammatory drugs blocked collagenase-induced oedema. Inhibition of endogenous kinin-releasing mechanisms by administration of hexadimethrine, a recognized inhibitor of the activation of clotting Factor XII, and depletion of kininogen by administration of carrageenin blocked collagenase-induced oedema. Collagenase did not increase permeability of rat skin vessels, nor did it release potential inflammatory mediators, such as bradykinin or prostaglandins, from plasma or platelets. Bacterial collagenase-induced haemorrhage presumably resulted from enzymatic destruction of membranous structures; at least a portion of the inflammatory response may be due to activation of a kinin-like system."}
{"id": "PMID:184704", "title": "Electrophysiologic effects of atropine on human sinus node and atrium.", "content": "Electrophysiologic studies were conducted in 17 patients without apparent sinus node disease before and after intravenous administration of 1 to 2 mg of atropine. Mean values in milliseconds (+/- standard error of the mean) before and after administration of atropine were as follows: sinus cycle length 846 +/- 26.4 versus 647 +/- 20.0 (P less than 0.001); sinus nodal recovery time 1,029 +/- 37 versus 774 +/- 36 (P less than 0.001); mean calculated sinoatrial (S-A) conduction time 103 +/- 5.7 versus 58 +/- 3.9 (P less than 0.001); mean P-A interval 34 +/- 1.5 msec versus 31 +/- 1.5 (P less than 0.05); mean atrial effective and functional refractory periods during sinus rhythm 285 +/- 11.3 versus 238 +/- 7.9 and 331 +/0 11.6 versus 280 +/- 8.6, respectively (P less than 0.001 for both); mean atrial effective and functional refractory periods measured at equivalent driven cycle length 239 +/- 7.7 versus 213 +/- 7.4 and 277 +/- 11.4 versus 245 +/- 9.5, respectively (P less than 0.001 for both). In conclusion, atropine shortened sinus cycle length, sinus nodal recovery time and calculated S-A conduction time. The shortening of atrial refractory periods with atropine implies that vagotonia prolongs atrial refractoriness in man.", "contents": "Electrophysiologic effects of atropine on human sinus node and atrium. Electrophysiologic studies were conducted in 17 patients without apparent sinus node disease before and after intravenous administration of 1 to 2 mg of atropine. Mean values in milliseconds (+/- standard error of the mean) before and after administration of atropine were as follows: sinus cycle length 846 +/- 26.4 versus 647 +/- 20.0 (P less than 0.001); sinus nodal recovery time 1,029 +/- 37 versus 774 +/- 36 (P less than 0.001); mean calculated sinoatrial (S-A) conduction time 103 +/- 5.7 versus 58 +/- 3.9 (P less than 0.001); mean P-A interval 34 +/- 1.5 msec versus 31 +/- 1.5 (P less than 0.05); mean atrial effective and functional refractory periods during sinus rhythm 285 +/- 11.3 versus 238 +/- 7.9 and 331 +/0 11.6 versus 280 +/- 8.6, respectively (P less than 0.001 for both); mean atrial effective and functional refractory periods measured at equivalent driven cycle length 239 +/- 7.7 versus 213 +/- 7.4 and 277 +/- 11.4 versus 245 +/- 9.5, respectively (P less than 0.001 for both). In conclusion, atropine shortened sinus cycle length, sinus nodal recovery time and calculated S-A conduction time. The shortening of atrial refractory periods with atropine implies that vagotonia prolongs atrial refractoriness in man."}
{"id": "PMID:184705", "title": "Significance of pacemaker recovery time after the Mustard operation for transposition of the great arteries.", "content": "Pacemaker recovery time corrected for cycle length was measured in 24 patients 6 months to 3 years after the Mustard operation for transposition of the great arteries. This index of sinoatrial (S-A) nodal function was obtained by subtracting the control R-R interval from the first R-R interval recorded after 3 minutes of rapid atrial pacing at the superior vena caval-right atrial junction. Recovery times were compared with those of a control group of 54 children with various forms of congenital heart disease who had not had cardiac surgery and whose electrocardiogram revealed normal sinus rhythm. The longest corrected pacemaker recovery time in the control group was 250 msec. Recovery time was normal (mean 115 msec) in 13 of the 24 patients who had undergone the Mustard procedure and prolonged (mean 472 msec) in the other 11. In 4 of these 11 a junctional escape complex was recorded before recovery of the S-A node. The configuration of the P wave and the development of dysrhythmias in the postoperative follow-up period were compared in patients with a normal and a prolonged corrected pacemaker recovery time. The incidence of dysrhythmias was much smaller in the former group. Normal sinus rhythm after the first postoperative week was noted in 10 (76 percent) of patients with a normal corrected pacemaker recovery time but in only 2 (18 percent) of those with an abnormal recovery time. One patient with an abnormal recovery time died suddenly 26 months after operation in spite of good hemodynamic repair. A prolonged pacemaker recovery time after the Mustard operation for transposition of the great arteries indicated that rhythm abnormalities were likely to develop, but a normal recovery time did not exclude abnormal sinus nodal function.", "contents": "Significance of pacemaker recovery time after the Mustard operation for transposition of the great arteries. Pacemaker recovery time corrected for cycle length was measured in 24 patients 6 months to 3 years after the Mustard operation for transposition of the great arteries. This index of sinoatrial (S-A) nodal function was obtained by subtracting the control R-R interval from the first R-R interval recorded after 3 minutes of rapid atrial pacing at the superior vena caval-right atrial junction. Recovery times were compared with those of a control group of 54 children with various forms of congenital heart disease who had not had cardiac surgery and whose electrocardiogram revealed normal sinus rhythm. The longest corrected pacemaker recovery time in the control group was 250 msec. Recovery time was normal (mean 115 msec) in 13 of the 24 patients who had undergone the Mustard procedure and prolonged (mean 472 msec) in the other 11. In 4 of these 11 a junctional escape complex was recorded before recovery of the S-A node. The configuration of the P wave and the development of dysrhythmias in the postoperative follow-up period were compared in patients with a normal and a prolonged corrected pacemaker recovery time. The incidence of dysrhythmias was much smaller in the former group. Normal sinus rhythm after the first postoperative week was noted in 10 (76 percent) of patients with a normal corrected pacemaker recovery time but in only 2 (18 percent) of those with an abnormal recovery time. One patient with an abnormal recovery time died suddenly 26 months after operation in spite of good hemodynamic repair. A prolonged pacemaker recovery time after the Mustard operation for transposition of the great arteries indicated that rhythm abnormalities were likely to develop, but a normal recovery time did not exclude abnormal sinus nodal function."}
{"id": "PMID:184706", "title": "Pathologic correlations in three cases of bilateral bundle branch disease with unusual electrophysiologic manifestations in two cases.", "content": "Examination of the conduction system in three patients with bifascicular block who had electrophysiologic studies forms the basis for this report. Patients 1 and 2 had left bundle branch block and Patient 3 right bundle branch block and left axis deviation. The H-V interval was prolonged in each case (70, 65 and 60 msec, respectively). Serial section examination of the conduction system revealed sclerodegenerative involvement of both bundle branches in all cases. In Case 1, atrial extrastimulus testing converted left to right bundle branch block; in Case 2, it delineated a sinus echo zone with repetitive sinus nodal reentrance. In the latter case serial section revealed extensive amyloid infiltration of the approaches to the sinoatrial (S-A) node and the atrial preferential pathways. In Case 3, with right bundle branch block and left axis deviation, serial section revealed greater involvement of the anterior part of the main left bundle branch than of the posterior portion as well as involvement of the second part of the right bundle branch. The study revealed excellent correlation between electrophysiologic and pathologic findings in three cases of intraventricular conduction disease and demonstrated an anatomic basis for the electrophysiologic findings resembling alternating bilateral bundle branch block. Sinus nodal reentrance may be related to disease in the approaches to the S-A node thereby causing delay in perinodal tissue allowing sinus reentrance. Finally in Case 3, the anatomic substrate for left axis deviation may lie in a greater involvement of the anterior portion than of the posterior portion of the main left bundle rather than in the corresponding portions of the periphery.", "contents": "Pathologic correlations in three cases of bilateral bundle branch disease with unusual electrophysiologic manifestations in two cases. Examination of the conduction system in three patients with bifascicular block who had electrophysiologic studies forms the basis for this report. Patients 1 and 2 had left bundle branch block and Patient 3 right bundle branch block and left axis deviation. The H-V interval was prolonged in each case (70, 65 and 60 msec, respectively). Serial section examination of the conduction system revealed sclerodegenerative involvement of both bundle branches in all cases. In Case 1, atrial extrastimulus testing converted left to right bundle branch block; in Case 2, it delineated a sinus echo zone with repetitive sinus nodal reentrance. In the latter case serial section revealed extensive amyloid infiltration of the approaches to the sinoatrial (S-A) node and the atrial preferential pathways. In Case 3, with right bundle branch block and left axis deviation, serial section revealed greater involvement of the anterior part of the main left bundle branch than of the posterior portion as well as involvement of the second part of the right bundle branch. The study revealed excellent correlation between electrophysiologic and pathologic findings in three cases of intraventricular conduction disease and demonstrated an anatomic basis for the electrophysiologic findings resembling alternating bilateral bundle branch block. Sinus nodal reentrance may be related to disease in the approaches to the S-A node thereby causing delay in perinodal tissue allowing sinus reentrance. Finally in Case 3, the anatomic substrate for left axis deviation may lie in a greater involvement of the anterior portion than of the posterior portion of the main left bundle rather than in the corresponding portions of the periphery."}
{"id": "PMID:184707", "title": "Intranuclear bodies in neurons of the periaqueductal gray matter in the cat.", "content": "The nucleoplasm of neurons in the nucleus lateralis of the periqueductal gray matter in the cat contains fibrillar structures which have no limiting membranes. These intranuclear bodies are associated with neither the nucleolus nor the nuclear membrane and have two characteristic forms. The first, the rodlet, is a compact bundle of fibrils 2 to 8 nm in diameter. It is usually elongated in shape although it appears spherical when sectioned transversely. This rod-like structure appears to correspond to Roncoroni's rodlet or the accessory body of Cajal in light microscopy. The second and more commonly observed form is a long slender bundle of five rows of parallel fibrils. Although similar intranuclear structures have frequently been observed in the highly differentiated neurons of the sympathetic ganglia and the retina, this is the first report of their pbesence in the undifferentiated neurons of the isodendritic core of the brainstem.", "contents": "Intranuclear bodies in neurons of the periaqueductal gray matter in the cat. The nucleoplasm of neurons in the nucleus lateralis of the periqueductal gray matter in the cat contains fibrillar structures which have no limiting membranes. These intranuclear bodies are associated with neither the nucleolus nor the nuclear membrane and have two characteristic forms. The first, the rodlet, is a compact bundle of fibrils 2 to 8 nm in diameter. It is usually elongated in shape although it appears spherical when sectioned transversely. This rod-like structure appears to correspond to Roncoroni's rodlet or the accessory body of Cajal in light microscopy. The second and more commonly observed form is a long slender bundle of five rows of parallel fibrils. Although similar intranuclear structures have frequently been observed in the highly differentiated neurons of the sympathetic ganglia and the retina, this is the first report of their pbesence in the undifferentiated neurons of the isodendritic core of the brainstem."}
{"id": "PMID:184708", "title": "Serum lipids in alcoholic patients with and without cirrhosis of the liver, with particular reference to endogenous familial hypertriglyceridemia.", "content": "The purpose of this study was to determine the frequency of hypertriglyceridemia in alcoholic patients with and without cirrhosis of the liver. It had been observed by others that subjects with endogenous familial hypertriglyceridemia (type IV hyperlipoproteinemia) showed an exaggerated lipidemic response to ingestion of alcohol, and, therefore, might be predisposed to hepatic cirrhosis. Comparison of 40 alcoholic cirrhotics with 40 noncirrhotic alcoholic patients showed no increased incidence of hypertriglyceridemia in either group. The findings suggest that the frequency of cirrhosis in the general population is not materially affected by subjects with this metabolic defect.", "contents": "Serum lipids in alcoholic patients with and without cirrhosis of the liver, with particular reference to endogenous familial hypertriglyceridemia. The purpose of this study was to determine the frequency of hypertriglyceridemia in alcoholic patients with and without cirrhosis of the liver. It had been observed by others that subjects with endogenous familial hypertriglyceridemia (type IV hyperlipoproteinemia) showed an exaggerated lipidemic response to ingestion of alcohol, and, therefore, might be predisposed to hepatic cirrhosis. Comparison of 40 alcoholic cirrhotics with 40 noncirrhotic alcoholic patients showed no increased incidence of hypertriglyceridemia in either group. The findings suggest that the frequency of cirrhosis in the general population is not materially affected by subjects with this metabolic defect."}
{"id": "PMID:184709", "title": "Cholangiocarcinoma as related to chronic intrahepatic cholangitis and hepatolithiasis. Case report and review of the literature.", "content": "A case of cholangiocarcinoma is described in a patient with underlying hepatic lithiasis and cholangitis. The possible pathogenesis of cholangiocarcinomas is discussed and the importance of endoscopic retrograde cholangiography in the diagnosis of this malignancy is emphasized.", "contents": "Cholangiocarcinoma as related to chronic intrahepatic cholangitis and hepatolithiasis. Case report and review of the literature. A case of cholangiocarcinoma is described in a patient with underlying hepatic lithiasis and cholangitis. The possible pathogenesis of cholangiocarcinomas is discussed and the importance of endoscopic retrograde cholangiography in the diagnosis of this malignancy is emphasized."}
{"id": "PMID:184710", "title": "Acute unilateral adrenal hemorrhage following ACTH administration in a patient with Cushing's syndrome.", "content": "A patient with Cushing's syndrome and a concomitant unilateral adrenal hemorrhage following ACTH administration is described. Although stress is commonly associated with the onset of adrenal hemorrhage, a pathologically documented adrenal hemorrhage has not been previously in association with ACTH administration in Cushing's syndrome. Repeated doses of ACTH should not be given to patients with Cushing's syndrome as this has little diagnostic value and may lead to adrenal hemorrhage in such patients.", "contents": "Acute unilateral adrenal hemorrhage following ACTH administration in a patient with Cushing's syndrome. A patient with Cushing's syndrome and a concomitant unilateral adrenal hemorrhage following ACTH administration is described. Although stress is commonly associated with the onset of adrenal hemorrhage, a pathologically documented adrenal hemorrhage has not been previously in association with ACTH administration in Cushing's syndrome. Repeated doses of ACTH should not be given to patients with Cushing's syndrome as this has little diagnostic value and may lead to adrenal hemorrhage in such patients."}
{"id": "PMID:184711", "title": "Therapeutic effects of heparin on Pseudomonas-induced corneal ulceration.", "content": "Fifty organisms of Pseudomonas aeruginosa were injected intralamellarly in both eyes of 60 albino rabbits. Twenty-four hours later, all eyes were graded and stratified into six groups of ten rabbits with equivalent infections. Treatment was begun with gentamicin alone or 0.3% polymyxin B alone, and in combination with acetylcysteine, 0.3M edetate disodium, and 2.500 units/ml of heparin sodium, four times daily. We also compared topical colistin and colistin and topical heparin. After two weeks, those corneas treated with polymyxin B and topical heparin showed a reduction in ulceration, corneal thinning, and descemetocele formation compared to those treated with polymyxin B alone. Based on these studies, heparin was administered topically, four times daily, to three patients with Pseudomonas-induced corneal ulcers in addition to antibiotics. Before treatment all corneas showed evidence of corneal liquefaction and two of the corneas were in imminent danger of perforation. After therapy, no corneas perforated; one patient recovered visual acuity of 6/9 (20/30), one patient recovered visual acuity of 6/6 (20/20) after keratoplasty, and the third has a vascularized leukoma.", "contents": "Therapeutic effects of heparin on Pseudomonas-induced corneal ulceration. Fifty organisms of Pseudomonas aeruginosa were injected intralamellarly in both eyes of 60 albino rabbits. Twenty-four hours later, all eyes were graded and stratified into six groups of ten rabbits with equivalent infections. Treatment was begun with gentamicin alone or 0.3% polymyxin B alone, and in combination with acetylcysteine, 0.3M edetate disodium, and 2.500 units/ml of heparin sodium, four times daily. We also compared topical colistin and colistin and topical heparin. After two weeks, those corneas treated with polymyxin B and topical heparin showed a reduction in ulceration, corneal thinning, and descemetocele formation compared to those treated with polymyxin B alone. Based on these studies, heparin was administered topically, four times daily, to three patients with Pseudomonas-induced corneal ulcers in addition to antibiotics. Before treatment all corneas showed evidence of corneal liquefaction and two of the corneas were in imminent danger of perforation. After therapy, no corneas perforated; one patient recovered visual acuity of 6/9 (20/30), one patient recovered visual acuity of 6/6 (20/20) after keratoplasty, and the third has a vascularized leukoma."}
{"id": "PMID:184712", "title": "Role of atrial receptors in the control of ACTH.", "content": "Sinusoidal volume changes (+/- 1 ml) were applied at 1 Hz to the right or left atrium of 25 anesthetized cats. Changes in firing rates of single vagal fibers and in plasma ACTH and cortisol were observed in response to start and stop of atrial pulsation. Decreased activity of right atrial and/or septal B-receptors was associated with increased ACTH. Changes in left atrial B-receptor activity were associated with a change in ACTH only if right atrial/septal receptors or baroreceptors also changed their activity in the same direction. The activity of atrial A-receptors did not change in response to atrial pulsation. A quantitative analysis suggested strongly that right atrial and/or septal B-receptors dominate in the response of ACTH to hemodynamic stimuli. Arterial receptors appear less effective, and left atrial B-receptors appear least effective in the hemodynamic control of ACTH.", "contents": "Role of atrial receptors in the control of ACTH. Sinusoidal volume changes (+/- 1 ml) were applied at 1 Hz to the right or left atrium of 25 anesthetized cats. Changes in firing rates of single vagal fibers and in plasma ACTH and cortisol were observed in response to start and stop of atrial pulsation. Decreased activity of right atrial and/or septal B-receptors was associated with increased ACTH. Changes in left atrial B-receptor activity were associated with a change in ACTH only if right atrial/septal receptors or baroreceptors also changed their activity in the same direction. The activity of atrial A-receptors did not change in response to atrial pulsation. A quantitative analysis suggested strongly that right atrial and/or septal B-receptors dominate in the response of ACTH to hemodynamic stimuli. Arterial receptors appear less effective, and left atrial B-receptors appear least effective in the hemodynamic control of ACTH."}
{"id": "PMID:184713", "title": "Identification and discharge patterns of spinal sympathetic interneurons.", "content": "Sympathetic interneurons, in the vicinity of the intermediolateral cell column of the cat thoracic spinal cord, were identified by determining whether the probability of spontaneously occurring unitary discharge was correlated in time with the R wave of the ECG. Fifteen units which could not be antidromically activated by stimulation of the cervical sympathetic nerve exhivited a positive post-R wave relationship. The discharge patterns of these cells were distinctly different from those of antidromically identified preganglionic neurons. The interneurons discharged spontaneously in bursts with short interspike intervals (less than 20 ms). Preganglionic neurons rarely discharged more than once during a cardiac cycle. Single shocks applied to medullary pressor sites evoked a train of spikes in the interneurons. Preganglionic units usually discharged only once to medullary pressor stimulation. Electrial activation of medullospinal inhibitory tracts suppressed the discharges of both interneurons and preganclionic units. This observation indicates that spinal inhibition is exerted at an interneuronal level within sympathoexictatory pathways. No evidence was found for the existence of inhibitory interneurons in the intermediolateral cell column. This study demonstrated that the post-R wave time interval histogram in combination with a test for antidromic activation can be used to differentiate between spinal sympathetic internuerons and preganglionic cells.", "contents": "Identification and discharge patterns of spinal sympathetic interneurons. Sympathetic interneurons, in the vicinity of the intermediolateral cell column of the cat thoracic spinal cord, were identified by determining whether the probability of spontaneously occurring unitary discharge was correlated in time with the R wave of the ECG. Fifteen units which could not be antidromically activated by stimulation of the cervical sympathetic nerve exhivited a positive post-R wave relationship. The discharge patterns of these cells were distinctly different from those of antidromically identified preganglionic neurons. The interneurons discharged spontaneously in bursts with short interspike intervals (less than 20 ms). Preganglionic neurons rarely discharged more than once during a cardiac cycle. Single shocks applied to medullary pressor sites evoked a train of spikes in the interneurons. Preganglionic units usually discharged only once to medullary pressor stimulation. Electrial activation of medullospinal inhibitory tracts suppressed the discharges of both interneurons and preganclionic units. This observation indicates that spinal inhibition is exerted at an interneuronal level within sympathoexictatory pathways. No evidence was found for the existence of inhibitory interneurons in the intermediolateral cell column. This study demonstrated that the post-R wave time interval histogram in combination with a test for antidromic activation can be used to differentiate between spinal sympathetic internuerons and preganglionic cells."}
{"id": "PMID:184714", "title": "Metabolic intermediates and lactate diffusion in active dog skeletal muscle.", "content": "The concentration of several metabolic intermediates, blood flow (Q), oxygen uptake (VO2), and lactate release (La) were measured in the gastrocnemius muscle of anesthetized dogs. Muscle lactate concentration increased from 1.6 to 2.7 mumol/g wet wt (P less than 0.05) during 0.5-5 min of contractions at 5 twitches/s but was not different from the contralateral resting muscle at 15, 30, or 60 min. Glycerophosphate increased from 0.35 to 0.70 mumol/g wet wt (P less than 0.05) during 0.5-5 min of activity, whereas muscle pyruvate decreased from 0.09 to 0.07 mumol/g wet wt (P less than 0.05). The concentration of NAD did not change in 9 of 11 experiments during contractions, despite a 12- to 15-fold increase in La. Significant decreases in NAD were observed when Q was compromised by arterial occlusion during contractions. No demonstrable relationship existed between La and either the muscle lactate concentration or muscle-venous lactate concentration gradient. Q was positively correlated with both La and muscle lactate during the first 5-15 min of activity. We conclude that increased La or increased lactate concentration in muscle need not be associated with hypoxia and that Q has a major influence on La.", "contents": "Metabolic intermediates and lactate diffusion in active dog skeletal muscle. The concentration of several metabolic intermediates, blood flow (Q), oxygen uptake (VO2), and lactate release (La) were measured in the gastrocnemius muscle of anesthetized dogs. Muscle lactate concentration increased from 1.6 to 2.7 mumol/g wet wt (P less than 0.05) during 0.5-5 min of contractions at 5 twitches/s but was not different from the contralateral resting muscle at 15, 30, or 60 min. Glycerophosphate increased from 0.35 to 0.70 mumol/g wet wt (P less than 0.05) during 0.5-5 min of activity, whereas muscle pyruvate decreased from 0.09 to 0.07 mumol/g wet wt (P less than 0.05). The concentration of NAD did not change in 9 of 11 experiments during contractions, despite a 12- to 15-fold increase in La. Significant decreases in NAD were observed when Q was compromised by arterial occlusion during contractions. No demonstrable relationship existed between La and either the muscle lactate concentration or muscle-venous lactate concentration gradient. Q was positively correlated with both La and muscle lactate during the first 5-15 min of activity. We conclude that increased La or increased lactate concentration in muscle need not be associated with hypoxia and that Q has a major influence on La."}
{"id": "PMID:184715", "title": "REM sleep and adaptation of psychiatric patients: an application of sleep studies.", "content": "The authors used sleep laboratory data to predict responses to psychiatric treatment. The predictions were based on the assumptions that REM latency reflects the need for dreaming and therefore the need for adaptation and that REM time reflects the capacity for the adaptive work associated with REM sleep. Dream recall and dream content were considered indicators of psychological mindedness and the patient's current conflicts. With this material, statistically significant predictions of such outcomes as good response to psychotherapy, elopement, or need for medication were made. The results of this study support the hypothesis that REM sleep is involved in adaptation.", "contents": "REM sleep and adaptation of psychiatric patients: an application of sleep studies. The authors used sleep laboratory data to predict responses to psychiatric treatment. The predictions were based on the assumptions that REM latency reflects the need for dreaming and therefore the need for adaptation and that REM time reflects the capacity for the adaptive work associated with REM sleep. Dream recall and dream content were considered indicators of psychological mindedness and the patient's current conflicts. With this material, statistically significant predictions of such outcomes as good response to psychotherapy, elopement, or need for medication were made. The results of this study support the hypothesis that REM sleep is involved in adaptation."}
{"id": "PMID:184716", "title": "Differential responding to the beta movement after waking from REM and nonREM sleep.", "content": "Ten young adults were wakened from REM sleep and from nonREM sleep on two nonconsecutive nights and were tested to determine their upper and lower beta-movement thresholds. The ranges of the illusion were found to be significantly wider after waking from REM sleep than after waking from nonREM sleep or before sleep. The differential responding to the beta movement supports the experimental hypothesis that apparent motion may provide sensitive detectors of the operation during wakefulness of the Basic Rest-Activity Cycle, of which REM and nonREM sleep are opposite phases that carry over into wakefulness.", "contents": "Differential responding to the beta movement after waking from REM and nonREM sleep. Ten young adults were wakened from REM sleep and from nonREM sleep on two nonconsecutive nights and were tested to determine their upper and lower beta-movement thresholds. The ranges of the illusion were found to be significantly wider after waking from REM sleep than after waking from nonREM sleep or before sleep. The differential responding to the beta movement supports the experimental hypothesis that apparent motion may provide sensitive detectors of the operation during wakefulness of the Basic Rest-Activity Cycle, of which REM and nonREM sleep are opposite phases that carry over into wakefulness."}
{"id": "PMID:184717", "title": "Extensive central nervous system calcification in a stillborn male infant due to cytomegalovirus infection.", "content": "The radiologic and pathologic findings of a stillborn male fetus with cytomegalic inclusion disease are described. Massive calcification of the cerebrum, cerebellum, eye (sclera and choroid), and spinal cord was present. There were unique deformities and apparent aplasia of some of the ribs. Classic intranuclear cytomegalic inclusion bodies were present primarily in the kidney. Routine radiography of stillborn infants is recommended for further study of intrauterine growth abnormalities.", "contents": "Extensive central nervous system calcification in a stillborn male infant due to cytomegalovirus infection. The radiologic and pathologic findings of a stillborn male fetus with cytomegalic inclusion disease are described. Massive calcification of the cerebrum, cerebellum, eye (sclera and choroid), and spinal cord was present. There were unique deformities and apparent aplasia of some of the ribs. Classic intranuclear cytomegalic inclusion bodies were present primarily in the kidney. Routine radiography of stillborn infants is recommended for further study of intrauterine growth abnormalities."}
{"id": "PMID:184720", "title": "Scanning electron microscopy of cell surfaces following removal of extracellular material.", "content": "The application of scanning electron microscopy to the study of cell surfaces is limited in intact tissues, because extracellular material may often obscure the details of nonluminal surfaces. To remove connective tissue elements we have treated human skin and both kidney, and an autonomic ganglion of the rat with hydrochloric acid and collagenase. Regional variations in the basal surface of the nephron are noted following removal of the basement membrane. The basilar interdigitations of the cells of the proximal tubule appeared as parallel ridges encircling the tubule. Ridges on the parietal epithelium of Bowman's capsule were randomly arranged and alternated with smooth surfaces. The dermal surface of the human epidermis has an alveolar or honeycomb appearance due to the elevation of the epidermal ridges and numerous pits for the dermal pegs. At higher magnifications the basal surface of cells of the stratum germinativum possessed numerous and irregular projections. Neurons with their processes are evident in the autonomic ganglion. The soma of the neurons are enclosed by flattened satellite cells. Irregular spaces between opposed satellite cells are interpreted as regions for the passage of processes related to the ganglion cells. Nodes of Ranvier were clearly seen along nerve fibers. Some pitting of the nerve fibers was also noted. The HCl-collagenase method has the advantage of the removal of collagen and basement membrane while preserving the structural integrity of the cell surface.", "contents": "Scanning electron microscopy of cell surfaces following removal of extracellular material. The application of scanning electron microscopy to the study of cell surfaces is limited in intact tissues, because extracellular material may often obscure the details of nonluminal surfaces. To remove connective tissue elements we have treated human skin and both kidney, and an autonomic ganglion of the rat with hydrochloric acid and collagenase. Regional variations in the basal surface of the nephron are noted following removal of the basement membrane. The basilar interdigitations of the cells of the proximal tubule appeared as parallel ridges encircling the tubule. Ridges on the parietal epithelium of Bowman's capsule were randomly arranged and alternated with smooth surfaces. The dermal surface of the human epidermis has an alveolar or honeycomb appearance due to the elevation of the epidermal ridges and numerous pits for the dermal pegs. At higher magnifications the basal surface of cells of the stratum germinativum possessed numerous and irregular projections. Neurons with their processes are evident in the autonomic ganglion. The soma of the neurons are enclosed by flattened satellite cells. Irregular spaces between opposed satellite cells are interpreted as regions for the passage of processes related to the ganglion cells. Nodes of Ranvier were clearly seen along nerve fibers. Some pitting of the nerve fibers was also noted. The HCl-collagenase method has the advantage of the removal of collagen and basement membrane while preserving the structural integrity of the cell surface."}
{"id": "PMID:184721", "title": "Studies of the dual effects of halothane on the lipolysis of human fat cells.", "content": "Halothane has dual effects on lipolysis of human adipose tissue: at low tissue concentrations a stimulatory effect is found, while at higher tissue concentrations lipolysis is inhibited. The lipolytic resonse of human adipose tissue was studied in vitro with or without halothane, the phosphodiesterase inhibitor theophylline, the lipase activator dibutyryl cAMP(dbcAMP), the alpha-receptor antagonist phentolamine, the nonselective beta-receptor antagonist propranolol, and the selective beta1-receptor antagonist practolol. In the absence of beta-receptor antagonists low concentrations of halothane stimulated lipolysis, This effect was blunted by beta-receptor antagonists, indicating that halothane at low tissue concentrations may directly stimulate the beta-receptors. The inhibitory effect of higher tissue concentrations of halothane was not the result of increased alpha-receptor activity since addition of phentolamine did not inhibit this effect. High concentrations of theophylline or dbcAMP increased lipolysis in specimens exposed to halothane, but the lipolytic rate was still less than that found in specimens not exposed to halothane. The data thus indicate that the inhibitory effect of halothane is exerted at a step beyond the formation and degradation of cAMP.", "contents": "Studies of the dual effects of halothane on the lipolysis of human fat cells. Halothane has dual effects on lipolysis of human adipose tissue: at low tissue concentrations a stimulatory effect is found, while at higher tissue concentrations lipolysis is inhibited. The lipolytic resonse of human adipose tissue was studied in vitro with or without halothane, the phosphodiesterase inhibitor theophylline, the lipase activator dibutyryl cAMP(dbcAMP), the alpha-receptor antagonist phentolamine, the nonselective beta-receptor antagonist propranolol, and the selective beta1-receptor antagonist practolol. In the absence of beta-receptor antagonists low concentrations of halothane stimulated lipolysis, This effect was blunted by beta-receptor antagonists, indicating that halothane at low tissue concentrations may directly stimulate the beta-receptors. The inhibitory effect of higher tissue concentrations of halothane was not the result of increased alpha-receptor activity since addition of phentolamine did not inhibit this effect. High concentrations of theophylline or dbcAMP increased lipolysis in specimens exposed to halothane, but the lipolytic rate was still less than that found in specimens not exposed to halothane. The data thus indicate that the inhibitory effect of halothane is exerted at a step beyond the formation and degradation of cAMP."}
{"id": "PMID:184724", "title": "[The enzymes of the enterocyte. Prospects for a functional exploration].", "content": "The authors recall the enzymatic activity and transport activities which were localised in the glycocalyx, the microvillous membrane, the intracellular compartment and the basolateral membrane of the enterocyte. The relationships between the processes of digestion and absorption, on the one hand, active transport, energy metabolism and sodium and potassium dependent ATPase, on the other hand are considered. The application of these data to functional investigation of the enterocyte is discussed, emphasizing the complementary character of the biological tests used currently and the importance of sodium and potassium dependent ATPase in the phenomena of active transport.", "contents": "[The enzymes of the enterocyte. Prospects for a functional exploration]. The authors recall the enzymatic activity and transport activities which were localised in the glycocalyx, the microvillous membrane, the intracellular compartment and the basolateral membrane of the enterocyte. The relationships between the processes of digestion and absorption, on the one hand, active transport, energy metabolism and sodium and potassium dependent ATPase, on the other hand are considered. The application of these data to functional investigation of the enterocyte is discussed, emphasizing the complementary character of the biological tests used currently and the importance of sodium and potassium dependent ATPase in the phenomena of active transport."}
{"id": "PMID:184726", "title": "Elevated serum angiotensin I converting enzyme in sarcoidosis.", "content": "Serum angiotensin I converting enzyme was found to be elevated in 56 patients with sarcoidosis (52.7 +/- 25.4 nmole per min per ml) compared to 84 normal control subjects (28.2 +/- 11.3 nmole per min per ml), 22 patients with tuberculosis (26.4 +/- 10.9 nmole per min per ml), and 20 patients with lymphomas (31.8 +/ 13.9 nmole per min per ml). Forty-eight per cent of the patients with sarcoidosis had values of enzymatic activity that were higher than 2 SD above the mean value of the control population; the false-positive rate in all nonsarcoidosis subjects combined was 5.5 per cent. Patients with parenchymal disease with or without hilar adenopathy had values somewhat higher than those with hilar adenopathy alone, but the difference was not significant (P less than 0.1). Patients with a known duration of disease greater than 2 years also had somewhat higher values than those with known disease less than 2 years, but the difference was not significant (P less than 0.1). There was no significant difference in values for patients receiving or not receiving steroids.", "contents": "Elevated serum angiotensin I converting enzyme in sarcoidosis. Serum angiotensin I converting enzyme was found to be elevated in 56 patients with sarcoidosis (52.7 +/- 25.4 nmole per min per ml) compared to 84 normal control subjects (28.2 +/- 11.3 nmole per min per ml), 22 patients with tuberculosis (26.4 +/- 10.9 nmole per min per ml), and 20 patients with lymphomas (31.8 +/ 13.9 nmole per min per ml). Forty-eight per cent of the patients with sarcoidosis had values of enzymatic activity that were higher than 2 SD above the mean value of the control population; the false-positive rate in all nonsarcoidosis subjects combined was 5.5 per cent. Patients with parenchymal disease with or without hilar adenopathy had values somewhat higher than those with hilar adenopathy alone, but the difference was not significant (P less than 0.1). Patients with a known duration of disease greater than 2 years also had somewhat higher values than those with known disease less than 2 years, but the difference was not significant (P less than 0.1). There was no significant difference in values for patients receiving or not receiving steroids."}
{"id": "PMID:184725", "title": "[Enzymopathic congenital hyperlactacidemia].", "content": "Congenital enzymopathic hyperlactacidemia results from a defect of utilisation of pyruvate either at the level of the pyruvate junction (pyruvate-carboxylase, pyruvate-dehydrogenase and Kreb's cycle), or at the level of the unidirectional enzymes on neo-glucogenesis and of neo-glycogenogenesis, e.g. glucose-6-phosphatase, phosphoenol-pyruvate-carboxykinase and glycogen synthetase. The enzymopathies which affect neoglucogenesis associate hyper-lactacidemia and fasting hypoglycemia and more or less marked hepatomegaly. Type I glycogenesis (von Gierke's disease) is the best known example. Enzymopathies which affect the pyruvate junction and the Krebs cycle, may be manifested in addition by: --either chronic neuropathies, e.g. Leigh's disease, recurrent ataxia, and moderate hyperalactacidemia,--or, as in congenital lactic acidoses, which have a rapid and severe prognosis with major hyperlactacidemia. Functional investigation, in particular, loading tests are of great value in orientation and justify the practice of tissue biopsy which permits the enzyme diagnosis. Recent, still unconfirmed knowledge of the pathogenesis of these diseases emphasizes the considerable importance of estimation of blood lactic acid in the investigation of metabolic acidoses of hereditary origin.", "contents": "[Enzymopathic congenital hyperlactacidemia]. Congenital enzymopathic hyperlactacidemia results from a defect of utilisation of pyruvate either at the level of the pyruvate junction (pyruvate-carboxylase, pyruvate-dehydrogenase and Kreb's cycle), or at the level of the unidirectional enzymes on neo-glucogenesis and of neo-glycogenogenesis, e.g. glucose-6-phosphatase, phosphoenol-pyruvate-carboxykinase and glycogen synthetase. The enzymopathies which affect neoglucogenesis associate hyper-lactacidemia and fasting hypoglycemia and more or less marked hepatomegaly. Type I glycogenesis (von Gierke's disease) is the best known example. Enzymopathies which affect the pyruvate junction and the Krebs cycle, may be manifested in addition by: --either chronic neuropathies, e.g. Leigh's disease, recurrent ataxia, and moderate hyperalactacidemia,--or, as in congenital lactic acidoses, which have a rapid and severe prognosis with major hyperlactacidemia. Functional investigation, in particular, loading tests are of great value in orientation and justify the practice of tissue biopsy which permits the enzyme diagnosis. Recent, still unconfirmed knowledge of the pathogenesis of these diseases emphasizes the considerable importance of estimation of blood lactic acid in the investigation of metabolic acidoses of hereditary origin."}
{"id": "PMID:184723", "title": "The biological effects of mineral fibres, especially asbestos, as seen from in vitro and in vivo studies.", "content": "Two in vitro models have been extensively used to compare the biological action of different types of asbestos fibres: the haemolytic effect and the cytotoxic one on macrophages grown in cell culture. The use of both techniques as led towards a better understanding of the chemical reactions which occur between fibres and the biological membranes of cells or intracellular organelles. Studies on the prevention of haemolysis and cytotoxicity have also been of use in explaining how asbestos acts a the cellular and molecular levels. Regarding in vivo studies, useful comparisons have been made of the fibrogenic and carcinogenic effects of different types of fibres in man and experimental animals. Both the in vitro and the in vivo aspects of the problem are discussed in some detail and an attemps is made to provide a reasonably unified concept for both.", "contents": "The biological effects of mineral fibres, especially asbestos, as seen from in vitro and in vivo studies. Two in vitro models have been extensively used to compare the biological action of different types of asbestos fibres: the haemolytic effect and the cytotoxic one on macrophages grown in cell culture. The use of both techniques as led towards a better understanding of the chemical reactions which occur between fibres and the biological membranes of cells or intracellular organelles. Studies on the prevention of haemolysis and cytotoxicity have also been of use in explaining how asbestos acts a the cellular and molecular levels. Regarding in vivo studies, useful comparisons have been made of the fibrogenic and carcinogenic effects of different types of fibres in man and experimental animals. Both the in vitro and the in vivo aspects of the problem are discussed in some detail and an attemps is made to provide a reasonably unified concept for both."}
{"id": "PMID:184727", "title": "The fine structure of lung macrophages from rhesus and squirrel monkeys, with special reference to the large numbers of mitochondria.", "content": "Alveolar macrophages from 2 species of nonhuman primates, rhesus and squirrel monkeys, were studied by electron microscopy. These macrophages seemed to differ from their counterparts in other animal species with respect to their large numbers of mitochondria. Monkey alveolar macrophages often contained crystalline material and a variety of inclusions in their cytoplasm, which did not seem to interfere with their phagocytic ability. The significance of these findings as they might relate to pulmonary infestation with mites and nematodes is discussed.", "contents": "The fine structure of lung macrophages from rhesus and squirrel monkeys, with special reference to the large numbers of mitochondria. Alveolar macrophages from 2 species of nonhuman primates, rhesus and squirrel monkeys, were studied by electron microscopy. These macrophages seemed to differ from their counterparts in other animal species with respect to their large numbers of mitochondria. Monkey alveolar macrophages often contained crystalline material and a variety of inclusions in their cytoplasm, which did not seem to interfere with their phagocytic ability. The significance of these findings as they might relate to pulmonary infestation with mites and nematodes is discussed."}
{"id": "PMID:184729", "title": "Benign liver tumors: what is their relationship to oral contraceptives?", "content": "A series of eight cases of benign hepatocellular tumors from the New Orleans area is presented. Clinical and histological features of these unusual tumors are discussed. Also, a series of 56 similar cases reported in the literature is reviewed. We conclude that these tumors have shown definite evidence of hormonal sensitivity and there is strong circumstantial evidence that oral contraceptive medications have contributed to their recent increased incidence. Although the risk of this problem in the overall population of women taking oral contraceptives seems to be quite small, further clinical and experimental research on this problem is clearly indicated.", "contents": "Benign liver tumors: what is their relationship to oral contraceptives? A series of eight cases of benign hepatocellular tumors from the New Orleans area is presented. Clinical and histological features of these unusual tumors are discussed. Also, a series of 56 similar cases reported in the literature is reviewed. We conclude that these tumors have shown definite evidence of hormonal sensitivity and there is strong circumstantial evidence that oral contraceptive medications have contributed to their recent increased incidence. Although the risk of this problem in the overall population of women taking oral contraceptives seems to be quite small, further clinical and experimental research on this problem is clearly indicated."}
{"id": "PMID:184730", "title": "The common hyperlipoproteinemias: an understanding of disease mechanisms and their control.", "content": "Our review focuses on low density lipoprotein (LD lipoprotein) and very low density lipoprotein (VLD lipoprotein) in their roles as transporters of cholesterol and triglyceride and as factors contributing to premature arteriovascular disease. We describe the clinical manifestations of the common, primary hyperlipoproteinemias--that is, hyper-beta-lipoproteinemia, combined hyperlipoproteinemia, hyper-pre-beta-lipoproteinemia, and sporadic hyperlipoproteinemia--and discuss the variations in lipoprotein structure and metabolism that occur in these diseases. Based on an understanding of the physiologic control of lipoprotein metabolism, it is possible for the physician to alter the concentrations of LD lipoprotein and VLD lipoprotein by selecting a course of therapy appropriate to the specific disease. We describe the effects of obesity, diet, insulin, ethanol, estrogens, and the drugs clofibrate, nicotinic acid, and cholestyramine.", "contents": "The common hyperlipoproteinemias: an understanding of disease mechanisms and their control. Our review focuses on low density lipoprotein (LD lipoprotein) and very low density lipoprotein (VLD lipoprotein) in their roles as transporters of cholesterol and triglyceride and as factors contributing to premature arteriovascular disease. We describe the clinical manifestations of the common, primary hyperlipoproteinemias--that is, hyper-beta-lipoproteinemia, combined hyperlipoproteinemia, hyper-pre-beta-lipoproteinemia, and sporadic hyperlipoproteinemia--and discuss the variations in lipoprotein structure and metabolism that occur in these diseases. Based on an understanding of the physiologic control of lipoprotein metabolism, it is possible for the physician to alter the concentrations of LD lipoprotein and VLD lipoprotein by selecting a course of therapy appropriate to the specific disease. We describe the effects of obesity, diet, insulin, ethanol, estrogens, and the drugs clofibrate, nicotinic acid, and cholestyramine."}
{"id": "PMID:184731", "title": "[The mechanism of releasing and bio-behavioral significance of the hypothalamo-hypophyso-adrenal gland reaction to the environment (alarm reaction)].", "content": "Laboratory experimentation has demonstrated the large increase in the rate of circulating norepinephrin (N.E.), in a parallel with an improvement in cardiovascular dynamism of suprarenalectomized rabbits under the action of injection IV of hydrocortisone. As from this ascertainment, the author attempts to make a synthesis of known experimental facts demonstrating that next to a regulation in constancy (with negative retroaction) of the C.R.F. leads to A.C.T.H. leads to cortisol system, there exists a servomechanism (control external to the system) as from the activity of the nervous systems as compared with environment. Hydrocortisone favouring passive avoidance, and extinction facilitating the activity of the cholinergic inhibiting system of action (I.S.A.). A.C.T.H. facilitates active avoidance and the catecholaminergic activating system of action (A.S.A.). Now, it has already been demonstrated in the same laboratory that stimulation of I.S.A. or inhibition of the A.S.A. freed N.E. from the peripherous nerves of a adrenalectomized animal. It, therefore, seems that the early freeing of A.C.T.H. following aggression is capable of favouring locomotive activity (flight or fight). Should the latter be efficient, there is a return to the prior behavioural and endocrinal balance. On the other hand, should they be inefficient, there arises a vicious circle (regulation with tendency, positive retroaction) because secondary secretion of glucocorticoids will maintain inhibition of action and the secondary freing of the mineralocorticoids are discussed as well as the central mechanism of illness so called \"psychosomatic\".", "contents": "[The mechanism of releasing and bio-behavioral significance of the hypothalamo-hypophyso-adrenal gland reaction to the environment (alarm reaction)]. Laboratory experimentation has demonstrated the large increase in the rate of circulating norepinephrin (N.E.), in a parallel with an improvement in cardiovascular dynamism of suprarenalectomized rabbits under the action of injection IV of hydrocortisone. As from this ascertainment, the author attempts to make a synthesis of known experimental facts demonstrating that next to a regulation in constancy (with negative retroaction) of the C.R.F. leads to A.C.T.H. leads to cortisol system, there exists a servomechanism (control external to the system) as from the activity of the nervous systems as compared with environment. Hydrocortisone favouring passive avoidance, and extinction facilitating the activity of the cholinergic inhibiting system of action (I.S.A.). A.C.T.H. facilitates active avoidance and the catecholaminergic activating system of action (A.S.A.). Now, it has already been demonstrated in the same laboratory that stimulation of I.S.A. or inhibition of the A.S.A. freed N.E. from the peripherous nerves of a adrenalectomized animal. It, therefore, seems that the early freeing of A.C.T.H. following aggression is capable of favouring locomotive activity (flight or fight). Should the latter be efficient, there is a return to the prior behavioural and endocrinal balance. On the other hand, should they be inefficient, there arises a vicious circle (regulation with tendency, positive retroaction) because secondary secretion of glucocorticoids will maintain inhibition of action and the secondary freing of the mineralocorticoids are discussed as well as the central mechanism of illness so called \"psychosomatic\"."}
{"id": "PMID:184735", "title": "Effect of disinfectants on variola virus in cell culture.", "content": "Twenty kinds of disinfectants were examined for ability to inactivate variola virus. Cytopathic effect and plaque formation on monolayer cultures of an established monkey kidney cell line were used as indicators of virus inactivation. A micromethod using microplate cultures, and not requiring a CO2 incubator, was adopted. The procedures were straightforward, showing good reproducibility. Among the compounds tested, several were found to be superior because of the minimum concentrations required for complete inactivation of virus. The purified viruses were shown to be more sensitive to the compounds than were the crude samples. The virus inactivation kinetics curves were determined by plaque counting. The usefulness of this method for quantitative analysis of disinfecting effect is suggested.", "contents": "Effect of disinfectants on variola virus in cell culture. Twenty kinds of disinfectants were examined for ability to inactivate variola virus. Cytopathic effect and plaque formation on monolayer cultures of an established monkey kidney cell line were used as indicators of virus inactivation. A micromethod using microplate cultures, and not requiring a CO2 incubator, was adopted. The procedures were straightforward, showing good reproducibility. Among the compounds tested, several were found to be superior because of the minimum concentrations required for complete inactivation of virus. The purified viruses were shown to be more sensitive to the compounds than were the crude samples. The virus inactivation kinetics curves were determined by plaque counting. The usefulness of this method for quantitative analysis of disinfecting effect is suggested."}
{"id": "PMID:184732", "title": "Laboratory diagnosis of foodborne diseases.", "content": "Many bacterial species are responsible for sporadic cases and outbreaks of foodborne intoxication and infection. The foodborne diseases are classified on the basis of the pathogenetic mechanisms involved into four categories: performed toxin, enterotoxin formed in the colonized small intestine, mucosal invasion (enterocolitis) and mucosal invasion with bacteremia. Invasive and toxigenic strains of enteropathogenic Escherichia coli are discussed. In vivo test systems for the identification of enterotoxigenic organisms and tissue culture assays for the heat-labile enterotoxin of E. coli are described. Current laboratory methods for the diagnosis of foodborne diseases of major public health interest are reviewed - botulism, staphylococcal intoxication, Clostridium perfringens enteritis, salmonellosis, enteropathogenic E. coli infection, Vibrio parahaemolyticus infection and Bacillus cereus enteritis. The role of the laboratory in the epidemiologic surveillance and investigation of foodborne diseases is emphasized.", "contents": "Laboratory diagnosis of foodborne diseases. Many bacterial species are responsible for sporadic cases and outbreaks of foodborne intoxication and infection. The foodborne diseases are classified on the basis of the pathogenetic mechanisms involved into four categories: performed toxin, enterotoxin formed in the colonized small intestine, mucosal invasion (enterocolitis) and mucosal invasion with bacteremia. Invasive and toxigenic strains of enteropathogenic Escherichia coli are discussed. In vivo test systems for the identification of enterotoxigenic organisms and tissue culture assays for the heat-labile enterotoxin of E. coli are described. Current laboratory methods for the diagnosis of foodborne diseases of major public health interest are reviewed - botulism, staphylococcal intoxication, Clostridium perfringens enteritis, salmonellosis, enteropathogenic E. coli infection, Vibrio parahaemolyticus infection and Bacillus cereus enteritis. The role of the laboratory in the epidemiologic surveillance and investigation of foodborne diseases is emphasized."}
{"id": "PMID:184736", "title": "Stability of human enteroviruses in estuarine and marine waters.", "content": "Studies of the effects of temperature and salinity on the survival of three enteric viruses (poliomyelitis type 1, echovirus-6, and coxsackievirus B-5) under controlled laboratory conditions and in situ indicate that temperature rather than salinity is the critical factor affecting their stability, in that the higher the temperature the more rapid was the loss of viral infectivity. In the laboratory studies, all three viruses were quite stable at 4 degrees C, with infectious virus still detectable after 46 weeks of incubation. In situ studies on virus survival in free-flowing estuarine or marine waters showed that, although the viruses were more labile in natural waters than in the laboratory studies, they persisted for several months, in some cases during the winter months. At all temperatures and salinities, coxsackievirus B-5 was the most stable, echovirus-6 was intermediate, and poliovirus 1 was the least stable of the viruses tested.", "contents": "Stability of human enteroviruses in estuarine and marine waters. Studies of the effects of temperature and salinity on the survival of three enteric viruses (poliomyelitis type 1, echovirus-6, and coxsackievirus B-5) under controlled laboratory conditions and in situ indicate that temperature rather than salinity is the critical factor affecting their stability, in that the higher the temperature the more rapid was the loss of viral infectivity. In the laboratory studies, all three viruses were quite stable at 4 degrees C, with infectious virus still detectable after 46 weeks of incubation. In situ studies on virus survival in free-flowing estuarine or marine waters showed that, although the viruses were more labile in natural waters than in the laboratory studies, they persisted for several months, in some cases during the winter months. At all temperatures and salinities, coxsackievirus B-5 was the most stable, echovirus-6 was intermediate, and poliovirus 1 was the least stable of the viruses tested."}
{"id": "PMID:184737", "title": "[Demonstration, by means of electron microscopy, of the penetration of somitic cells into the mesoblast of the limb buds of reptile embryos (Anguis fragilis, Lacerta viridis)].", "content": "An electron microscopic study of the components of anterior limb buds of the slow-worm (Anguis fragilis) and of the green lizard (Lacerta viridis) (embryos of Anguis whose allantoic bud reach 0,7 to 4 mm of length; embryos of Lacerta 2 to 7 days old) provides data on the cytological characteristics of the components of the limb bud at these early stages. 1. The cells of the distal extremity of the somitic processes extending in the limb bud of Anguis and Lacerta, are elongated cells with ovoid nuclei containing large nucleolus; they possess mitochondria always thin and with dense matrix; they are rich in lipid droplets; they possess cilia; they are devoid of myofilaments; endoplasmic reticulum, free ribosomes and polyribosomes are abundant. Golgi networks display signs of activity. These characteristics are also observed in the cells of the \"dermatome\" layer of the dermo-myotome; and so, it appears probable that the cells of the \"dermatome\". Furthermore, in Anguis embryos, the cells of the distal extremities of the somitic processes possess numerous lysosomes and a certain number of cells among them, degenerate early. 2. The somatopleural mesoblastic cells of the limb bud of Anguis and Lacerta embryos keep the characters of the cells of the mesodermic layer of lateral plate from which they originate; they have rounded nuclei, cilia, and their mitochondria are always larger and more transparent to electrons, than the ones of cells of the somitic processes and of cells of the epiblastic apical crest. Golgi networks are well developped, endoplasmic reticulum is abundant, lipid droplets are rare. 3. The processes of somites which extend in the dorsal part of the limb bud of Anguis embryos are cords of cells with thin lumina; at the stage of the allantoic bud of 0,6 to 0,8 mm long, the distal extremity of these processes dislocate in group of cells which afterwards dissociate, releasing individual somitic cells which are integrated among the mesoblastic somatopleural cells. In young lizard embryos (2 to 4 days old) the distal extremity of the somitic processes enlarges into a vesicle from which cells are released and penetrate in the mesoblast of the limb bud. 4. The somitic cells released from the somitic processes of Anguis and Lacerta keep--at least at early stages--the cytological characteristics they displayed when they were still in situ in the somitic processes: grounded on the presence or absence of lipid droplets, on the width and density of the mitochondria, the distinction, at these stages, between the somitic and mesoblastic somatoplerual cells is possible; and it is also possible to observe the integration of the somitic cells into the mesoblast. This study brings the demonstration of the cellular contribution of the somites to the formation of the limb bud in Reptiles. 5...", "contents": "[Demonstration, by means of electron microscopy, of the penetration of somitic cells into the mesoblast of the limb buds of reptile embryos (Anguis fragilis, Lacerta viridis)]. An electron microscopic study of the components of anterior limb buds of the slow-worm (Anguis fragilis) and of the green lizard (Lacerta viridis) (embryos of Anguis whose allantoic bud reach 0,7 to 4 mm of length; embryos of Lacerta 2 to 7 days old) provides data on the cytological characteristics of the components of the limb bud at these early stages. 1. The cells of the distal extremity of the somitic processes extending in the limb bud of Anguis and Lacerta, are elongated cells with ovoid nuclei containing large nucleolus; they possess mitochondria always thin and with dense matrix; they are rich in lipid droplets; they possess cilia; they are devoid of myofilaments; endoplasmic reticulum, free ribosomes and polyribosomes are abundant. Golgi networks display signs of activity. These characteristics are also observed in the cells of the \"dermatome\" layer of the dermo-myotome; and so, it appears probable that the cells of the \"dermatome\". Furthermore, in Anguis embryos, the cells of the distal extremities of the somitic processes possess numerous lysosomes and a certain number of cells among them, degenerate early. 2. The somatopleural mesoblastic cells of the limb bud of Anguis and Lacerta embryos keep the characters of the cells of the mesodermic layer of lateral plate from which they originate; they have rounded nuclei, cilia, and their mitochondria are always larger and more transparent to electrons, than the ones of cells of the somitic processes and of cells of the epiblastic apical crest. Golgi networks are well developped, endoplasmic reticulum is abundant, lipid droplets are rare. 3. The processes of somites which extend in the dorsal part of the limb bud of Anguis embryos are cords of cells with thin lumina; at the stage of the allantoic bud of 0,6 to 0,8 mm long, the distal extremity of these processes dislocate in group of cells which afterwards dissociate, releasing individual somitic cells which are integrated among the mesoblastic somatopleural cells. In young lizard embryos (2 to 4 days old) the distal extremity of the somitic processes enlarges into a vesicle from which cells are released and penetrate in the mesoblast of the limb bud. 4. The somitic cells released from the somitic processes of Anguis and Lacerta keep--at least at early stages--the cytological characteristics they displayed when they were still in situ in the somitic processes: grounded on the presence or absence of lipid droplets, on the width and density of the mitochondria, the distinction, at these stages, between the somitic and mesoblastic somatoplerual cells is possible; and it is also possible to observe the integration of the somitic cells into the mesoblast. This study brings the demonstration of the cellular contribution of the somites to the formation of the limb bud in Reptiles. 5..."}
{"id": "PMID:184745", "title": "Cytology of rheumatoid synovial cells in culture. IV. Further investigations of cell lines cocultivated with rheumatoid synovial cells.", "content": "A previous report described a cell isolate presumed to have arisen by accidental cocultivation (contamination) of the Chang 'liver' cell line and rheumatoid synovial cells. This cell isolate had the same glucose-6-phosphate dehydrogenase isoenzyme as the Chang cell and also some shared antigens. It clearly differed in its karyotype, its ability to grow in semisolid agar, and in the possession of bleb-like projections of the cytoplasmic membrane filled with collections of beaded or granular material. In addition, it had a novel antigen(s) not present in the Chang cell. As these properties might have been acquired from the synovial cells and because the bleb structures resembled those seen in some cell lines transformed by leucovirus the cell isolate has been further studied. Cytochemical methods at the light and electron microscope level showed that the granular material was polysaccharide in nature, probably glycogen. No evidence was found of the presence of a virus or a viral genome using a variety of techniques including attempted induction followed by 3H-uridine labelling of the cultures, and assay of the supernatant fluid from the culture for viral RNA-dependent DNA polymerase. In addition, cell extracts were not found to contain viral RNA-dependent DNA polymerase or RNA-dependent RNA polymerase. No rubella virus or leucovirus interspecies antigens were detected on the cell membranes.", "contents": "Cytology of rheumatoid synovial cells in culture. IV. Further investigations of cell lines cocultivated with rheumatoid synovial cells. A previous report described a cell isolate presumed to have arisen by accidental cocultivation (contamination) of the Chang 'liver' cell line and rheumatoid synovial cells. This cell isolate had the same glucose-6-phosphate dehydrogenase isoenzyme as the Chang cell and also some shared antigens. It clearly differed in its karyotype, its ability to grow in semisolid agar, and in the possession of bleb-like projections of the cytoplasmic membrane filled with collections of beaded or granular material. In addition, it had a novel antigen(s) not present in the Chang cell. As these properties might have been acquired from the synovial cells and because the bleb structures resembled those seen in some cell lines transformed by leucovirus the cell isolate has been further studied. Cytochemical methods at the light and electron microscope level showed that the granular material was polysaccharide in nature, probably glycogen. No evidence was found of the presence of a virus or a viral genome using a variety of techniques including attempted induction followed by 3H-uridine labelling of the cultures, and assay of the supernatant fluid from the culture for viral RNA-dependent DNA polymerase. In addition, cell extracts were not found to contain viral RNA-dependent DNA polymerase or RNA-dependent RNA polymerase. No rubella virus or leucovirus interspecies antigens were detected on the cell membranes."}
{"id": "PMID:184747", "title": "Preferred surgical treatment for alveolar cell carcinoma.", "content": "An analysis of our experience with 48 patients having bronchiolar or alveolar cell carcinoma is reported. The remarkable biological variability of this peripheral tumor has important surgical implications. Basically, two dominant clinical presentations occur. In the less common diffuse or multinodular form, prolonged survival is infrequent regardless of the therapeutic approach. Often these patients die from respiratory compromise due to the tumor itself. In the more common localized or solitary form the prognosis for cure is good, approximating 47% or higher. Based on the material presented, lobectomy is the preferred method of surgical treatment. In patients manifesting multinodular disease, surgical resection rarely seems warranted. The concept of preserving pulmonary tissue is stressed.", "contents": "Preferred surgical treatment for alveolar cell carcinoma. An analysis of our experience with 48 patients having bronchiolar or alveolar cell carcinoma is reported. The remarkable biological variability of this peripheral tumor has important surgical implications. Basically, two dominant clinical presentations occur. In the less common diffuse or multinodular form, prolonged survival is infrequent regardless of the therapeutic approach. Often these patients die from respiratory compromise due to the tumor itself. In the more common localized or solitary form the prognosis for cure is good, approximating 47% or higher. Based on the material presented, lobectomy is the preferred method of surgical treatment. In patients manifesting multinodular disease, surgical resection rarely seems warranted. The concept of preserving pulmonary tissue is stressed."}
{"id": "PMID:184748", "title": "Granular cell myoblastoma of the bronchus: report of 2 cases and review of the literature.", "content": "Granular cell myoblastoma of the bronchus is rare. Two patients are described, bringing the total reported to 44. Review of the literature shows that cough, chest pain, hemoptysis, and wheezing are frequent presenting symptoms and that distal atelectasis and recurrent or persistent pneumonitis are common roentgenographic findings. Though the histogenesis of this tumor remains controversial, most pathologists now believe that the cells have a neurogenic origin. Adequate open surgical resection is the treatment of choice.", "contents": "Granular cell myoblastoma of the bronchus: report of 2 cases and review of the literature. Granular cell myoblastoma of the bronchus is rare. Two patients are described, bringing the total reported to 44. Review of the literature shows that cough, chest pain, hemoptysis, and wheezing are frequent presenting symptoms and that distal atelectasis and recurrent or persistent pneumonitis are common roentgenographic findings. Though the histogenesis of this tumor remains controversial, most pathologists now believe that the cells have a neurogenic origin. Adequate open surgical resection is the treatment of choice."}
{"id": "PMID:184749", "title": "Nephrogenous cyclic AMP levels in primary hyperparathyroidism.", "content": "The clinical utility of urinary cyclic adenosine-3',5'-monophosphate (cAMP) determinations has been limited by the overlap between hyperparathyroid and normal patients. We evaluated the potential of the parathyroid hormone (PTH)-dependent, nephrogenous cAMP in the diagnosis of hyperparathyroidism. Twenty-three patients with primary hyperparathyroidism and 19 control subjects had two-hour urine collections and blood sampling at midpoint. Nephrogenous cAMP level was calculated as total urinary cAMP excretion minus the amount filtered. The total urinary cAMP excretion (micromols per gram of creatinine) was higher in hyperparathyroid patients (6.8 +/- .5 SE), but overlapped with values obtained in controls (2.9 +/- .15). The level of nephrogenous cAMP (percent of total) was also higher in hyperparathyroid patients (72.5 +/- 1.8) than controls (26.3 +/- 4.1) and clearly separated the groups. Determination of nephrogenous cAMP levels may be useful in the diagnosis of hyperparathyroidism.", "contents": "Nephrogenous cyclic AMP levels in primary hyperparathyroidism. The clinical utility of urinary cyclic adenosine-3',5'-monophosphate (cAMP) determinations has been limited by the overlap between hyperparathyroid and normal patients. We evaluated the potential of the parathyroid hormone (PTH)-dependent, nephrogenous cAMP in the diagnosis of hyperparathyroidism. Twenty-three patients with primary hyperparathyroidism and 19 control subjects had two-hour urine collections and blood sampling at midpoint. Nephrogenous cAMP level was calculated as total urinary cAMP excretion minus the amount filtered. The total urinary cAMP excretion (micromols per gram of creatinine) was higher in hyperparathyroid patients (6.8 +/- .5 SE), but overlapped with values obtained in controls (2.9 +/- .15). The level of nephrogenous cAMP (percent of total) was also higher in hyperparathyroid patients (72.5 +/- 1.8) than controls (26.3 +/- 4.1) and clearly separated the groups. Determination of nephrogenous cAMP levels may be useful in the diagnosis of hyperparathyroidism."}
{"id": "PMID:184746", "title": "[Presence of cytomegalovirus in maternal milk].", "content": "The AA. make in evidence the role of the milk as carrier of Cytomegalovirus. The virus was isolated in the 23.5% of the 17 specimens of milk examinated within the first 48 hours from the delivery. The contemporary observation of the urins of the womans was negative.", "contents": "[Presence of cytomegalovirus in maternal milk]. The AA. make in evidence the role of the milk as carrier of Cytomegalovirus. The virus was isolated in the 23.5% of the 17 specimens of milk examinated within the first 48 hours from the delivery. The contemporary observation of the urins of the womans was negative."}
{"id": "PMID:184750", "title": "[200 valvular disorders seen in Abidjan].", "content": "The authors have made a retrospective study of the case notes of 200 patients with valvular disorders seen over the course of 35 months (excluding those due to constrictive endocardial fibrosis). The cases represent the frequency of cardiac failure, especially in the mitral group. The authors found 61% to have mitral valve disease, 28.5% aortic valve disease, and 9.5% disease of more than one valve. Mitral valve lesions were found most frequently in young females (average age 26 years); aortic valve lesions were found more commonly in an older age group of men (average age 47 years). The authors discuss the aetiology. Rheumatic fever was responsible in 60% of cases, and caused particularly mitral valve disease. Atherosclerosis and syphilis were the commonest causes in the aortic group. Indications for surgery were found in 74 cases (37%), and 28% of these were closed heart techniques. The course of the disease is best appreciated during the first hospital admission. The mortality rate was 5.5%, and most of the patients (65%) were stabilised on treatment.", "contents": "[200 valvular disorders seen in Abidjan]. The authors have made a retrospective study of the case notes of 200 patients with valvular disorders seen over the course of 35 months (excluding those due to constrictive endocardial fibrosis). The cases represent the frequency of cardiac failure, especially in the mitral group. The authors found 61% to have mitral valve disease, 28.5% aortic valve disease, and 9.5% disease of more than one valve. Mitral valve lesions were found most frequently in young females (average age 26 years); aortic valve lesions were found more commonly in an older age group of men (average age 47 years). The authors discuss the aetiology. Rheumatic fever was responsible in 60% of cases, and caused particularly mitral valve disease. Atherosclerosis and syphilis were the commonest causes in the aortic group. Indications for surgery were found in 74 cases (37%), and 28% of these were closed heart techniques. The course of the disease is best appreciated during the first hospital admission. The mortality rate was 5.5%, and most of the patients (65%) were stabilised on treatment."}
{"id": "PMID:184751", "title": "[Pseudohypothyroidism. Complementary results apropos of 4 familial cases].", "content": "In a sibship, 4 out of 5 children featured pseudo-hypoparathyroidism. The following points were verified: hypocalcaemia; increase of the serum level of PTH; normal response of bone and gut effectors to endegenous PTH; contrast between normal bone X-rays and lesions detected by histological studies.", "contents": "[Pseudohypothyroidism. Complementary results apropos of 4 familial cases]. In a sibship, 4 out of 5 children featured pseudo-hypoparathyroidism. The following points were verified: hypocalcaemia; increase of the serum level of PTH; normal response of bone and gut effectors to endegenous PTH; contrast between normal bone X-rays and lesions detected by histological studies."}
{"id": "PMID:184752", "title": "[Tumor hyperacidulation through glucose infusion enhanced by nicotinamide adenine dinucleotide (author's transl)].", "content": "Tumor peracidity in Walker carcinosarcoma 256-bearing Wistar rats attained by glucose (Gk) infusion was significantly (t-Test; p = 3.49) increased by a following infusion of 200 mg NAD in 7 ml 40 per cent. Gk-solution. The mean pH values obtained on six animals amounted 6.88 (start), 5.21 (after Gk) and 5.79 (after Gk + NAD). Three animals were cured through the hyperacidification process.", "contents": "[Tumor hyperacidulation through glucose infusion enhanced by nicotinamide adenine dinucleotide (author's transl)]. Tumor peracidity in Walker carcinosarcoma 256-bearing Wistar rats attained by glucose (Gk) infusion was significantly (t-Test; p = 3.49) increased by a following infusion of 200 mg NAD in 7 ml 40 per cent. Gk-solution. The mean pH values obtained on six animals amounted 6.88 (start), 5.21 (after Gk) and 5.79 (after Gk + NAD). Three animals were cured through the hyperacidification process."}
{"id": "PMID:184753", "title": "Scanning electron microscopic observation on intracellular structures of ion-etched materials.", "content": "Ion-etching technique on the cracked surface of biological material may give a plastic visualization of intracellular structures under the scanning electron microscope, because membraneous structures in the cell are generally etch-resistant and the cytoplasmic matrix is easily ion-etched. Mild ion-etching using low voltage was applied to the cells of the pancreas. Nuclear pores were clearly disclosed but were enlarged slightly in the process of etching. Endoplasmic reticulum with ribosomes, Golgi apparatus, mitochondria, some filamentous structures and crystalline inclusions (B cell granules) were also effectively disclosed by ion-etching technique. It is necessary, however, to compare the etched specimens carefully with non-etched ones to determine whether given structures observed are intrinsic ones or artifacts caused by etching.", "contents": "Scanning electron microscopic observation on intracellular structures of ion-etched materials. Ion-etching technique on the cracked surface of biological material may give a plastic visualization of intracellular structures under the scanning electron microscope, because membraneous structures in the cell are generally etch-resistant and the cytoplasmic matrix is easily ion-etched. Mild ion-etching using low voltage was applied to the cells of the pancreas. Nuclear pores were clearly disclosed but were enlarged slightly in the process of etching. Endoplasmic reticulum with ribosomes, Golgi apparatus, mitochondria, some filamentous structures and crystalline inclusions (B cell granules) were also effectively disclosed by ion-etching technique. It is necessary, however, to compare the etched specimens carefully with non-etched ones to determine whether given structures observed are intrinsic ones or artifacts caused by etching."}
{"id": "PMID:184754", "title": "Nerve conduction velocity measurements: improved accuracy using superimposed response waves.", "content": "A new procedure of serial motor nerve conduction velocity (NCV) measurements with the use of \"superimposed response waves\" technique (or double stimulus technique) was performed on 29 normal subjects. Six peripheral nerves were tested once a week for four to six weeks. A total of 760 NCV measurements were thus obtained to try to assess the magnitude of error in serial NCV testings. With the double stimulus technique employed, a significant reduction in variations of serial NCV measurements was found. The overall standard deviation of four to six consecutive NCV measurements in the 34 subjects was 1.3 meters per second with a coefficient of variation of 2.4%. These findings obtained with the double stimulus technique have proven to be approximately three times more accurate than results obtained by investigators who studied nerve conduction velocity measurement variation with single stimulus standard NCV testing techniques.", "contents": "Nerve conduction velocity measurements: improved accuracy using superimposed response waves. A new procedure of serial motor nerve conduction velocity (NCV) measurements with the use of \"superimposed response waves\" technique (or double stimulus technique) was performed on 29 normal subjects. Six peripheral nerves were tested once a week for four to six weeks. A total of 760 NCV measurements were thus obtained to try to assess the magnitude of error in serial NCV testings. With the double stimulus technique employed, a significant reduction in variations of serial NCV measurements was found. The overall standard deviation of four to six consecutive NCV measurements in the 34 subjects was 1.3 meters per second with a coefficient of variation of 2.4%. These findings obtained with the double stimulus technique have proven to be approximately three times more accurate than results obtained by investigators who studied nerve conduction velocity measurement variation with single stimulus standard NCV testing techniques."}
{"id": "PMID:184756", "title": "Intraductal \"noninfiltrating\" carcinoma of the breast.", "content": "We are reviewing 40 patients with noninvasive intraductal carcients; 10% developed oppostie breast cancer of the invasive variety. Twenty-one patients underwent radical mastectomy in which one patient was found to have a positive axillary node. The 19 remaining patients had total mastectomy alone. No recurrence of death attributed to intraductal carcinoma was found in 39 patients available for follow-up.", "contents": "Intraductal \"noninfiltrating\" carcinoma of the breast. We are reviewing 40 patients with noninvasive intraductal carcients; 10% developed oppostie breast cancer of the invasive variety. Twenty-one patients underwent radical mastectomy in which one patient was found to have a positive axillary node. The 19 remaining patients had total mastectomy alone. No recurrence of death attributed to intraductal carcinoma was found in 39 patients available for follow-up."}
{"id": "PMID:184758", "title": "[Interrelationship between the quality of dietary protein and the function of the adrenal cortex. 3. Reactivity of the adrenal cortex and ACTH content of the pituitary gland of rats fed with proteins of various quality].", "content": "Trials were performed investigating the reactivity of the adrenals and the ACTH content of the pituitary gland in rats fed proteins of varying quality. A positive correlation was found to exist between the relative weight of the adrenals and the rate of body weight increases as well as between the weight of the pituitary gland and the rate of body weight gains. In either case this process was found to be primarily dependent on the quality of the dietary protein. It was shown that the quality of the dietary protein did not affect the in vitro reactivity of the adrenal glands. The ACTH content of the pituitary gland( determined on the basis of 100 mg of pituitary tissue) did not change considerably.", "contents": "[Interrelationship between the quality of dietary protein and the function of the adrenal cortex. 3. Reactivity of the adrenal cortex and ACTH content of the pituitary gland of rats fed with proteins of various quality]. Trials were performed investigating the reactivity of the adrenals and the ACTH content of the pituitary gland in rats fed proteins of varying quality. A positive correlation was found to exist between the relative weight of the adrenals and the rate of body weight increases as well as between the weight of the pituitary gland and the rate of body weight gains. In either case this process was found to be primarily dependent on the quality of the dietary protein. It was shown that the quality of the dietary protein did not affect the in vitro reactivity of the adrenal glands. The ACTH content of the pituitary gland( determined on the basis of 100 mg of pituitary tissue) did not change considerably."}
{"id": "PMID:184755", "title": "[Acid phosphatase activity in breast dysplasias and in carcinomas of the breast].", "content": "The histochemical reactions of acid phosphatase were studied in tissues deriving from normal breasts, from mammary dysplasia, and from breast carcinoma. Acid phosphatase was demonstrated in all cases with more intense activity in breast carcinoma where activity was particularly accentuated in the stroma. In benign tumours and fibroadenosis, phosphatase was prevalently localized in the periductal cells and within the ducts. Exceptions were the cases of fibroadenosis with acute or chronic collateral inflammation where phosphatase granules were located in the stroma also, even though they were always quantitatively inferior to the corresponding localization of cases of breast carcinomas.", "contents": "[Acid phosphatase activity in breast dysplasias and in carcinomas of the breast]. The histochemical reactions of acid phosphatase were studied in tissues deriving from normal breasts, from mammary dysplasia, and from breast carcinoma. Acid phosphatase was demonstrated in all cases with more intense activity in breast carcinoma where activity was particularly accentuated in the stroma. In benign tumours and fibroadenosis, phosphatase was prevalently localized in the periductal cells and within the ducts. Exceptions were the cases of fibroadenosis with acute or chronic collateral inflammation where phosphatase granules were located in the stroma also, even though they were always quantitatively inferior to the corresponding localization of cases of breast carcinomas."}
{"id": "PMID:184759", "title": "Antibody class and complement requirement of neutralizing antibodies in the primary and secondary antibody response of cattle to infectious bovine rhinotracheitis virus vaccine.", "content": "Calves responded to a single intramuscular injection of an attenuated strain of infectious bovine rhinotracheitis virus by producing IgM followed by IgG antibody. Both IgM and IgG antibody produced during the first month were primarily complement-requiring neutralizing antibody (CRNAb), especially IgM antibody. After a month, IgG had replaced IgM as the predominant immunoglobulin, and titers with and without complement (C') decreased in both IgG and IgM fractions. The largest decrease was in the IgM CRNAb fraction. Seven days after a second injection given on day 196, calves responded with an anamnestic IgG response in which CRNAb titers were 1 or 2 two-fold dilutions higher than non-CRNAb titers. One calf developed an IgM response similar to its primary response, whereas inhibition of the IgM response occurred in the other 3 calves which had much lower IgM antibody titers than those attained in the primary response. Twenty-eight days after the second injection the titers of IgG were the same or only a 2-fold dilution less than their 7-day secondary titers, whereas IgM titers generally decreased considerably more than this. Guinea pig and rabbit sera were equally effective as C' sources in potentiating CRNAb, whereas bovine serum was a poor C' source.", "contents": "Antibody class and complement requirement of neutralizing antibodies in the primary and secondary antibody response of cattle to infectious bovine rhinotracheitis virus vaccine. Calves responded to a single intramuscular injection of an attenuated strain of infectious bovine rhinotracheitis virus by producing IgM followed by IgG antibody. Both IgM and IgG antibody produced during the first month were primarily complement-requiring neutralizing antibody (CRNAb), especially IgM antibody. After a month, IgG had replaced IgM as the predominant immunoglobulin, and titers with and without complement (C') decreased in both IgG and IgM fractions. The largest decrease was in the IgM CRNAb fraction. Seven days after a second injection given on day 196, calves responded with an anamnestic IgG response in which CRNAb titers were 1 or 2 two-fold dilutions higher than non-CRNAb titers. One calf developed an IgM response similar to its primary response, whereas inhibition of the IgM response occurred in the other 3 calves which had much lower IgM antibody titers than those attained in the primary response. Twenty-eight days after the second injection the titers of IgG were the same or only a 2-fold dilution less than their 7-day secondary titers, whereas IgM titers generally decreased considerably more than this. Guinea pig and rabbit sera were equally effective as C' sources in potentiating CRNAb, whereas bovine serum was a poor C' source."}
{"id": "PMID:184760", "title": "Anti-viral activity against encephalomyocarditis virus and Semliki Forest virus and acute toxicity of poly I and poly C administered sequentially to mice.", "content": "Mice are protected against lethal intraperitoneal and intravenous infection by encephalomyocarditis virus and Semliki Forest virus by sequential treatment with poly I followed by either polyC or poly5-hydroxyC without production of interferon when the treatments are 4 or more hours apart and by the intraperitoneal or intravenous routes. Maximum protection occurs around 4 hours before infection and is still significant 20 hours after infection. Treatments with combinations of other homoribopolynucleotides were not found to be anti-viral. Protection by sequential polyI, polyC treatment of mice is relatively short-lived and does not 'hypo-reactivate' the protective effect of polyI:C and shows approximately half the protective effect of polyI:C. The toxicity of sequential polyI, polyC treatment is lower than that of polyI:C particularly if poly5-hydroxyC is substituted for polyC. Silica treatment of mice indicates that stationary macrophages are required for protection by polyI followed by polyC but an effect on humoral or cell mediated immune responses does not appear to be involved. The effect appears to be a synergism between the protection conferred by polyI or polyC alone.", "contents": "Anti-viral activity against encephalomyocarditis virus and Semliki Forest virus and acute toxicity of poly I and poly C administered sequentially to mice. Mice are protected against lethal intraperitoneal and intravenous infection by encephalomyocarditis virus and Semliki Forest virus by sequential treatment with poly I followed by either polyC or poly5-hydroxyC without production of interferon when the treatments are 4 or more hours apart and by the intraperitoneal or intravenous routes. Maximum protection occurs around 4 hours before infection and is still significant 20 hours after infection. Treatments with combinations of other homoribopolynucleotides were not found to be anti-viral. Protection by sequential polyI, polyC treatment of mice is relatively short-lived and does not 'hypo-reactivate' the protective effect of polyI:C and shows approximately half the protective effect of polyI:C. The toxicity of sequential polyI, polyC treatment is lower than that of polyI:C particularly if poly5-hydroxyC is substituted for polyC. Silica treatment of mice indicates that stationary macrophages are required for protection by polyI followed by polyC but an effect on humoral or cell mediated immune responses does not appear to be involved. The effect appears to be a synergism between the protection conferred by polyI or polyC alone."}
{"id": "PMID:184761", "title": "Potentiation of poly I:C induced viral resistance by polycationic modified polypeptides.", "content": "The potentiation of polyI:C induced viral resistance by various side group modified polycationic polyglutamic acid derivatives was investigated. It was established that the efficacy of the various polycationic substances depends primarily on their macromolecular properties. Viscosity and the degree of cationic substitution have been found to be of paramount importance. The maximal potentiating efficacy, expressed as the minimum protective dose of polyI:C necessary for complete protection of cells in the presence of the polycations, was exerted by compounds of highest viscosity and degree of subsitution. The potentiating efficacy of the polycationic derivatives tested could only be observed in a relatively narrow range of concentration, depending on their viscosity and degree of substitution. In view of the extremely low minimal protective dose of polyI:C (10(-5) mug/ml) in the presence of our most effective compound it is assumed that the action of a few molecules of polyI:C may be sufficient to render a cell resistant against viral infection. Within the limits of the described experiments, the efficacy of polycationic derivatives did not seem to be influenced by the modification (e.g. quaternarization) of the cationic group.", "contents": "Potentiation of poly I:C induced viral resistance by polycationic modified polypeptides. The potentiation of polyI:C induced viral resistance by various side group modified polycationic polyglutamic acid derivatives was investigated. It was established that the efficacy of the various polycationic substances depends primarily on their macromolecular properties. Viscosity and the degree of cationic substitution have been found to be of paramount importance. The maximal potentiating efficacy, expressed as the minimum protective dose of polyI:C necessary for complete protection of cells in the presence of the polycations, was exerted by compounds of highest viscosity and degree of subsitution. The potentiating efficacy of the polycationic derivatives tested could only be observed in a relatively narrow range of concentration, depending on their viscosity and degree of substitution. In view of the extremely low minimal protective dose of polyI:C (10(-5) mug/ml) in the presence of our most effective compound it is assumed that the action of a few molecules of polyI:C may be sufficient to render a cell resistant against viral infection. Within the limits of the described experiments, the efficacy of polycationic derivatives did not seem to be influenced by the modification (e.g. quaternarization) of the cationic group."}
{"id": "PMID:184762", "title": "Surface antigens on HeLa cells persistently infected with HVJ (Sendai virus).", "content": "Surface antigens of HeLaHVJ cells, a cell line persistently infected with HVJ, were studied by fluorescent antibody staining. After absorption with concentrated HVJ virions and HeLa cells, anti-HeLaHVJ antiserum was able to demonstrate specific surface fluorescence on HeLaHVJ cells, while this serum no longer reacted with original HeLa cells nor with HVJ virions. During cytolytic infection of HeLa cells with HVJ, this specific surface antigen appeared at an early stage of infection prior to the appearance of newly synthesized HVJ viral antigens and moreover appeared in spite of the inhibition of viral protein synthesis. This antigen was detected neither on HeLa cells infected with other myxoviruses except HVJ nor on various other kinds of cells infected with HVJ. The specific surface antigen was still found on the HeLaHVJ cell surface after incubation at 38 degrees C for two days, while HVJ structural antigens on the cell surface no longer could be detected. Mild short-term treatment of HeLa cells with trypsin, neuraminidase from vibrio cholerae, phospholipase-C and hyaluronidase failed to expose specific antigen. The antigen was distinguishable from the Forssman and human blood type antigens. The mechanism of appearance of a new antigen on the surface of HeLaHVJ cells remains unclear.", "contents": "Surface antigens on HeLa cells persistently infected with HVJ (Sendai virus). Surface antigens of HeLaHVJ cells, a cell line persistently infected with HVJ, were studied by fluorescent antibody staining. After absorption with concentrated HVJ virions and HeLa cells, anti-HeLaHVJ antiserum was able to demonstrate specific surface fluorescence on HeLaHVJ cells, while this serum no longer reacted with original HeLa cells nor with HVJ virions. During cytolytic infection of HeLa cells with HVJ, this specific surface antigen appeared at an early stage of infection prior to the appearance of newly synthesized HVJ viral antigens and moreover appeared in spite of the inhibition of viral protein synthesis. This antigen was detected neither on HeLa cells infected with other myxoviruses except HVJ nor on various other kinds of cells infected with HVJ. The specific surface antigen was still found on the HeLaHVJ cell surface after incubation at 38 degrees C for two days, while HVJ structural antigens on the cell surface no longer could be detected. Mild short-term treatment of HeLa cells with trypsin, neuraminidase from vibrio cholerae, phospholipase-C and hyaluronidase failed to expose specific antigen. The antigen was distinguishable from the Forssman and human blood type antigens. The mechanism of appearance of a new antigen on the surface of HeLaHVJ cells remains unclear."}
{"id": "PMID:184763", "title": "Localisation on foot-and-mouth disease virus (FMDV) of an antigenic deficiency induced by passage in BHK cells.", "content": "Passage of FMDV in BHK suspended cells was confirmed to induce an antigenic deficiency on the virion. By immunodiffusion experiments with complete virus, with trypsin-treated virus and with 12S virus fraction it was shown that the induced antigenic deficiency is located on the trypsin-removable part of the virion. These results were confirmed by absorption experiments.", "contents": "Localisation on foot-and-mouth disease virus (FMDV) of an antigenic deficiency induced by passage in BHK cells. Passage of FMDV in BHK suspended cells was confirmed to induce an antigenic deficiency on the virion. By immunodiffusion experiments with complete virus, with trypsin-treated virus and with 12S virus fraction it was shown that the induced antigenic deficiency is located on the trypsin-removable part of the virion. These results were confirmed by absorption experiments."}
{"id": "PMID:184764", "title": "Pinwheel inclusions in morphogenesis: a possible alternative to induction by viruses.", "content": "Pinwheel inclusions (PWs) were found in cells of callus tissue derived from explants of secondary phloem parenchyma of carrot (Daucus carota) storage root and grown on a basal medium containing zeatin and indoleacetic acid or coconut milk, naphthalene acetic acid, or combinations of these. Preliminary attempts to demonstrate the presence of viruses in the callus tissue failed. The possibility that the tissles were infected by a low titer or unstable conventional virus or by a defective mutant has not been ruled out. However, two lines of evidence suggest that the PWs in these tissues may be a result of culture conditions and not of virus infection. First, no PWs or other cytoplasmic inclusions were found in cells of otherwise similar tissue cultured on basal medium alone, and multifibrillar bundles (MFBs) but not PWs were found when the tissues were cultured on a medium that stimulates differentiation and morphogenesis. Second, culture stimulated to differentiate and containing MFBs only were returned to the supplemented basal medium and subsequently found to contain both PWs and MFBs.", "contents": "Pinwheel inclusions in morphogenesis: a possible alternative to induction by viruses. Pinwheel inclusions (PWs) were found in cells of callus tissue derived from explants of secondary phloem parenchyma of carrot (Daucus carota) storage root and grown on a basal medium containing zeatin and indoleacetic acid or coconut milk, naphthalene acetic acid, or combinations of these. Preliminary attempts to demonstrate the presence of viruses in the callus tissue failed. The possibility that the tissles were infected by a low titer or unstable conventional virus or by a defective mutant has not been ruled out. However, two lines of evidence suggest that the PWs in these tissues may be a result of culture conditions and not of virus infection. First, no PWs or other cytoplasmic inclusions were found in cells of otherwise similar tissue cultured on basal medium alone, and multifibrillar bundles (MFBs) but not PWs were found when the tissues were cultured on a medium that stimulates differentiation and morphogenesis. Second, culture stimulated to differentiate and containing MFBs only were returned to the supplemented basal medium and subsequently found to contain both PWs and MFBs."}
{"id": "PMID:184766", "title": "Bilateral sixth nerve palsy. Analysis of 125 cases.", "content": "Bilateral abducens nerve pareses were nearly as common as unilateral cases in an inpatient setting (125:143). Cerebrospinal fluid abnormalities were more frequent among the bilateral cases, but generally the same causes produced unilateral and bilateral sixth nerve palsy. The relative ease of diagnosis was in contrast with the large number of undiagnosed or \"vascular\" cases in previous studies of outpatients. The degree of lateral rectus limitation proved to be of limited help in suggesting the cause or predicting recovery of oculomotor function. The etiology was of some prognostic value, with universal recovery of pressure palsies and rare improvement with tumor involvement. Myasthenia, orbital muscle entrapment, convergence spasm, divergence palsy, and pretectal pseudoconvergence entered into the differential diagnosis, but were only occasionally difficult to exclude.", "contents": "Bilateral sixth nerve palsy. Analysis of 125 cases. Bilateral abducens nerve pareses were nearly as common as unilateral cases in an inpatient setting (125:143). Cerebrospinal fluid abnormalities were more frequent among the bilateral cases, but generally the same causes produced unilateral and bilateral sixth nerve palsy. The relative ease of diagnosis was in contrast with the large number of undiagnosed or \"vascular\" cases in previous studies of outpatients. The degree of lateral rectus limitation proved to be of limited help in suggesting the cause or predicting recovery of oculomotor function. The etiology was of some prognostic value, with universal recovery of pressure palsies and rare improvement with tumor involvement. Myasthenia, orbital muscle entrapment, convergence spasm, divergence palsy, and pretectal pseudoconvergence entered into the differential diagnosis, but were only occasionally difficult to exclude."}
{"id": "PMID:184767", "title": "Familial fingerprint body myopathy.", "content": "Muscle biopsy specimens from two half brothers with a congenital benign muscle disorder and from their mother, clinically unaffected, were studied by histochemistry and electron microscopy. In the children's biopsy specimens, the ultrastructural examination showed numerous fingerprint bodies located at the periphery of the muscle fibers. The histochemical pattern was different in these two specimens. In the mother's biopsy specimen, while fingerprint bodies were not found, the muscle fibers showed slight but definite changes. Even if the fingerprint bodies by themselves are not specific for a particular muscle disease, their occurrence in two half brothers is a valid argument in favor of the individalization of the fingerprint body myopathy, which has been previously described.", "contents": "Familial fingerprint body myopathy. Muscle biopsy specimens from two half brothers with a congenital benign muscle disorder and from their mother, clinically unaffected, were studied by histochemistry and electron microscopy. In the children's biopsy specimens, the ultrastructural examination showed numerous fingerprint bodies located at the periphery of the muscle fibers. The histochemical pattern was different in these two specimens. In the mother's biopsy specimen, while fingerprint bodies were not found, the muscle fibers showed slight but definite changes. Even if the fingerprint bodies by themselves are not specific for a particular muscle disease, their occurrence in two half brothers is a valid argument in favor of the individalization of the fingerprint body myopathy, which has been previously described."}
{"id": "PMID:184770", "title": "Herpes simplex virus in human cornea, retrocorneal fibrous membrane, and vitreous.", "content": "A case of recurrent herpes simplex virus keratouveitis was studied using both electron microscopic and viral culture techniques. We describe a patient who had a particularly violent course, including three failed grafts, endophthalmitis, and wound leak. We report the identification of virus in a quiescent failed corneal graft and retrocorneal membrane; persistence of virus enabling its culture from the vitreous; and electron microscopic identification in the cornea removed at the third transplant. The identification of cases in which viral proliferation occurs is necessary for a greater understanding of the pathogenesis of herpetic corneal disease and for determining in which particular patient steroid therapy should be avoided.", "contents": "Herpes simplex virus in human cornea, retrocorneal fibrous membrane, and vitreous. A case of recurrent herpes simplex virus keratouveitis was studied using both electron microscopic and viral culture techniques. We describe a patient who had a particularly violent course, including three failed grafts, endophthalmitis, and wound leak. We report the identification of virus in a quiescent failed corneal graft and retrocorneal membrane; persistence of virus enabling its culture from the vitreous; and electron microscopic identification in the cornea removed at the third transplant. The identification of cases in which viral proliferation occurs is necessary for a greater understanding of the pathogenesis of herpetic corneal disease and for determining in which particular patient steroid therapy should be avoided."}
{"id": "PMID:184771", "title": "Human conjunctivitis. II. Treatment.", "content": "One hundred forty-three patients (207 eyes) with conjunctivitis or blepharoconjunctivitis were investigated to determine (1) the safety of topical corticosteroid therapy and the relative efficacy of formulations of increasing potency and (2) the effectiveness of a steroid-antibiotic preparation compared to each of its components alone and to a placebo. The corticosteroids were equally effective in suppressing conjunctival inflammation; all were more effective than the placebo. Active conjunctivitis was controlled more readily by those preparations containing a steroid, both alone and in combination. The corticosteroid alone (dexamethasone) was more effective in producing inactivation of conjunctivitis than the antibiotic alone ( a mixture of neomycin sulfate and polymyxin B sulfate). This observation remained unchanged when cases of Staphylococcus aureus conjunctivitis were analyzed separately. No serious complications resulted from any treatment regimen.", "contents": "Human conjunctivitis. II. Treatment. One hundred forty-three patients (207 eyes) with conjunctivitis or blepharoconjunctivitis were investigated to determine (1) the safety of topical corticosteroid therapy and the relative efficacy of formulations of increasing potency and (2) the effectiveness of a steroid-antibiotic preparation compared to each of its components alone and to a placebo. The corticosteroids were equally effective in suppressing conjunctival inflammation; all were more effective than the placebo. Active conjunctivitis was controlled more readily by those preparations containing a steroid, both alone and in combination. The corticosteroid alone (dexamethasone) was more effective in producing inactivation of conjunctivitis than the antibiotic alone ( a mixture of neomycin sulfate and polymyxin B sulfate). This observation remained unchanged when cases of Staphylococcus aureus conjunctivitis were analyzed separately. No serious complications resulted from any treatment regimen."}
{"id": "PMID:184772", "title": "Malignant Glomus vagale: report of a case and review of the literature.", "content": "Tumors of the chemoreceptor system are quite rare, and are usually considered to be benign, but locally invasive. We report a case of a glomus juxtavagale tumor with metastasis to cervical lymph nodes, lung, and bone. Review of the literature shows that 19% of similar cases reported also showed distant metastases, a rate significantly higher than for other chemodectomas. Clinically and histologically, benign and malignant tumors are identical, so only the demonstration of distant metastasis indicates malignant neoplasm. Primary treatment is surgical, but radiotherapy is useful for palliation.", "contents": "Malignant Glomus vagale: report of a case and review of the literature. Tumors of the chemoreceptor system are quite rare, and are usually considered to be benign, but locally invasive. We report a case of a glomus juxtavagale tumor with metastasis to cervical lymph nodes, lung, and bone. Review of the literature shows that 19% of similar cases reported also showed distant metastases, a rate significantly higher than for other chemodectomas. Clinically and histologically, benign and malignant tumors are identical, so only the demonstration of distant metastasis indicates malignant neoplasm. Primary treatment is surgical, but radiotherapy is useful for palliation."}
{"id": "PMID:184773", "title": "Changes in plasma lipoproteins in subjects treated with the bile acid-sequestering resin polidexide (Secholex).", "content": "The effects of a new anion-exchange resin, polidexide, 3-30 grams/day, on plasma lipids and lipoproteins have been studied in one normal subject and in three hyperlipidaemic patients. Plasma cholesterol concentrations were significantly reduced in all subjects over 80-120 days of therapy by amounts ranging from 14 to 20%. Plasma triglyceride concentrations increased in two patients with pre-existing hypertriglyceridaemia. Plasma apolipoprotein-B concentrations were reduced in all subjects. Cholesterol and apo-B concentrations in low density lipoproteins were reduced in all subjects, while triglyceride concentrations in very low density lipoproteins were increased in 3/4 subjects; Changes in high density lipoproteins were quite variable.", "contents": "Changes in plasma lipoproteins in subjects treated with the bile acid-sequestering resin polidexide (Secholex). The effects of a new anion-exchange resin, polidexide, 3-30 grams/day, on plasma lipids and lipoproteins have been studied in one normal subject and in three hyperlipidaemic patients. Plasma cholesterol concentrations were significantly reduced in all subjects over 80-120 days of therapy by amounts ranging from 14 to 20%. Plasma triglyceride concentrations increased in two patients with pre-existing hypertriglyceridaemia. Plasma apolipoprotein-B concentrations were reduced in all subjects. Cholesterol and apo-B concentrations in low density lipoproteins were reduced in all subjects, while triglyceride concentrations in very low density lipoproteins were increased in 3/4 subjects; Changes in high density lipoproteins were quite variable."}
{"id": "PMID:184774", "title": "A mucosal disease virus infection of the pregnant ewe as a cause of a border disease-like condition.", "content": "An experiment was designed to investigate whether a condition in Australian sheep with clinical and pathological similarites to Border Disease was caused by the infection of the pregnant ewe with a Mucosal Disease virus (MDV). Forty ewes, at 58 to 63 days after mating, were inoculated with material from lambs in which all, some or none of the tissues examined contained MDV. The clinical condition was observed only in lambs born to ewes inoculated with MDV-positive material and then only to ewes in the group which had serological evidence of MDV infection. It is concluded that the Border Disease-like condition in Australian sheep is caused by the infection of the pregnant ewe with a Mucosal Disease virus.", "contents": "A mucosal disease virus infection of the pregnant ewe as a cause of a border disease-like condition. An experiment was designed to investigate whether a condition in Australian sheep with clinical and pathological similarites to Border Disease was caused by the infection of the pregnant ewe with a Mucosal Disease virus (MDV). Forty ewes, at 58 to 63 days after mating, were inoculated with material from lambs in which all, some or none of the tissues examined contained MDV. The clinical condition was observed only in lambs born to ewes inoculated with MDV-positive material and then only to ewes in the group which had serological evidence of MDV infection. It is concluded that the Border Disease-like condition in Australian sheep is caused by the infection of the pregnant ewe with a Mucosal Disease virus."}
{"id": "PMID:184776", "title": "Space flight effects on the skeletal muscles of rats.", "content": "Morphological and histochemical examinations of the skeletal muscles of rats flown for 22 d aboard the Cosmos-605 biosatellite have demonstrated atrophic and dystrophic developments in the soleus muscle accompanied by metabolic changes in the muscle tissue. The changes were reversible but did not disappear entirely 27 d postflight. Early atrophic developments were seen in the m. gastrocnemius, m. quadriceps, and m. ext. digitorum longus on the second postflight day. The comparative study of the muscles of flight and simulation rats has shown that pathology developed in the muscles as a result of diminished motor activity of animals being aggravated by weightlessness.", "contents": "Space flight effects on the skeletal muscles of rats. Morphological and histochemical examinations of the skeletal muscles of rats flown for 22 d aboard the Cosmos-605 biosatellite have demonstrated atrophic and dystrophic developments in the soleus muscle accompanied by metabolic changes in the muscle tissue. The changes were reversible but did not disappear entirely 27 d postflight. Early atrophic developments were seen in the m. gastrocnemius, m. quadriceps, and m. ext. digitorum longus on the second postflight day. The comparative study of the muscles of flight and simulation rats has shown that pathology developed in the muscles as a result of diminished motor activity of animals being aggravated by weightlessness."}
{"id": "PMID:184778", "title": "[Cystinosis (author's transl)].", "content": "Cystinosis (syn. crystine storage disease) is inherited as an autosomal recessive trait. The severety of clinical symptoms may vary considerably. The most severe form of nephropathic cystinosis causes death of the affected patients at the age of 2 to 4 years (subacute course) or before puberty (primary chronical course). Three autopsy cases are demonstrated. Each of these children died from complications of chronic renal failure, caused by kidney contraction as a sequela of chronic interstitial nephritis. Cristalline cystine deposits were found in the renal interstium as well as in the RES cells of spleen and liver. Because of water solubility of L-cystine aqueous fixation and staining solutions must be avoided. Diagnostic doubly refractive brick- or needle-shaped cystine cristals can be demonstrated in frozen sections or tissue smears from spleen, liver, lymphnode and bone marrow.", "contents": "[Cystinosis (author's transl)]. Cystinosis (syn. crystine storage disease) is inherited as an autosomal recessive trait. The severety of clinical symptoms may vary considerably. The most severe form of nephropathic cystinosis causes death of the affected patients at the age of 2 to 4 years (subacute course) or before puberty (primary chronical course). Three autopsy cases are demonstrated. Each of these children died from complications of chronic renal failure, caused by kidney contraction as a sequela of chronic interstitial nephritis. Cristalline cystine deposits were found in the renal interstium as well as in the RES cells of spleen and liver. Because of water solubility of L-cystine aqueous fixation and staining solutions must be avoided. Diagnostic doubly refractive brick- or needle-shaped cystine cristals can be demonstrated in frozen sections or tissue smears from spleen, liver, lymphnode and bone marrow."}
{"id": "PMID:184779", "title": "Electrophoretic variability in island populations of Drosophila simulans and Drosophila immigrans.", "content": "Genetic structure and variability were investigated in several Hawaiian populations of D. simulans and D. immigrans. Genetic variability is lower in Hawaiian populations of D. simulans than in Texas populations, and allelic differences exist as well. For D. immigrans, Hawaiian and Korean populations are similar in variability, allelic content, and gene frequencies. Several hypothesis are advanced to account for the patterns in gene variation observed between island and continental populations of these two colonizing species.", "contents": "Electrophoretic variability in island populations of Drosophila simulans and Drosophila immigrans. Genetic structure and variability were investigated in several Hawaiian populations of D. simulans and D. immigrans. Genetic variability is lower in Hawaiian populations of D. simulans than in Texas populations, and allelic differences exist as well. For D. immigrans, Hawaiian and Korean populations are similar in variability, allelic content, and gene frequencies. Several hypothesis are advanced to account for the patterns in gene variation observed between island and continental populations of these two colonizing species."}
{"id": "PMID:184791", "title": "Substrate cycles in metabolic regulation and in heat generation.", "content": "1. The presence of substrate cycles in tissues has been demonstrated by direct isotope methods in recent years. This demonstration has provided the impetus for a reappraisal of the roles of substrate cycling in metabolic regulation and in heat production. These aspects of substrate cycling are discussed in this paper. The relationship between near-equilibrium reactions and substrate cycles is emphasized, since this provides a basis for the derivation of a function describing in precise quantitative terms the factors governing the amplification provided by substrate cycles in metabolic regulation. Some examples of the roles of substrate cycles in providing sensitivity in metabolic regulation are described. The importance of substrate cycling in heat generation in the flight muscle of the bumble-bee and in brown adipose tissue is discussed in detail. 2. We point out that the two possible roles of cycling, heat production and amplification, are intimately linked so that they must be discussed together. It is proposed that variable rates of substrate cycling may be possible so that, for short periods of time. sensitivity can be maximal without excessive heat generation. Variable rates over the long term may be involved in weight control, and the control of such variability in cycling rates may be impaired in obese subjects. Finally, the possibilities that substrate cycles provide explanations for the specific dynamic action of food and for alcoholic and accidental hypothermia are raised.", "contents": "Substrate cycles in metabolic regulation and in heat generation. 1. The presence of substrate cycles in tissues has been demonstrated by direct isotope methods in recent years. This demonstration has provided the impetus for a reappraisal of the roles of substrate cycling in metabolic regulation and in heat production. These aspects of substrate cycling are discussed in this paper. The relationship between near-equilibrium reactions and substrate cycles is emphasized, since this provides a basis for the derivation of a function describing in precise quantitative terms the factors governing the amplification provided by substrate cycles in metabolic regulation. Some examples of the roles of substrate cycles in providing sensitivity in metabolic regulation are described. The importance of substrate cycling in heat generation in the flight muscle of the bumble-bee and in brown adipose tissue is discussed in detail. 2. We point out that the two possible roles of cycling, heat production and amplification, are intimately linked so that they must be discussed together. It is proposed that variable rates of substrate cycling may be possible so that, for short periods of time. sensitivity can be maximal without excessive heat generation. Variable rates over the long term may be involved in weight control, and the control of such variability in cycling rates may be impaired in obese subjects. Finally, the possibilities that substrate cycles provide explanations for the specific dynamic action of food and for alcoholic and accidental hypothermia are raised."}
{"id": "PMID:184797", "title": "The affinity of low density lipoproteins for an arterial macromolecular complex. A study in ischemic heart disease and controls.", "content": "Levels of serum cholesterol, triglycerides, lipoprotein pattern and the insolubilization of serum low density lipoproteins (LDL, betalipoprotein) by a factor present in arterial intima--media extracts was investigated in 55 patients with acute coronary heart disease and 50 healthy controls. In blood samples obtained 24 h after the episode, the serum betalipoproteins from male normotensive patients showed a high tendency to precipitate when incubated with the intima-media extracts, nearly twice the value measured in the control group. This affinity returned almost to control level after 21 days in the hospital. Hypertensive patients showed a serum cholesterol higher than the controls but almost no difference in LDL-arterial factor interaction. The composition of isolated LDL was studied in 7 patients and 8 controls and it was found that the total cholesterol/protein plus phospholipid ratio has a positive exponential correlation with the lipoprotein-arterial factor affinity. The results of LDL analyses suggest that a change in their composition, frequent in normotensive patients, can lead to an increased affinity of this lipoprotein for arterial intimamedia components. It is proposed that this process could be an additional risk factor contributing to the deposition of LDL in the arterial wall.", "contents": "The affinity of low density lipoproteins for an arterial macromolecular complex. A study in ischemic heart disease and controls. Levels of serum cholesterol, triglycerides, lipoprotein pattern and the insolubilization of serum low density lipoproteins (LDL, betalipoprotein) by a factor present in arterial intima--media extracts was investigated in 55 patients with acute coronary heart disease and 50 healthy controls. In blood samples obtained 24 h after the episode, the serum betalipoproteins from male normotensive patients showed a high tendency to precipitate when incubated with the intima-media extracts, nearly twice the value measured in the control group. This affinity returned almost to control level after 21 days in the hospital. Hypertensive patients showed a serum cholesterol higher than the controls but almost no difference in LDL-arterial factor interaction. The composition of isolated LDL was studied in 7 patients and 8 controls and it was found that the total cholesterol/protein plus phospholipid ratio has a positive exponential correlation with the lipoprotein-arterial factor affinity. The results of LDL analyses suggest that a change in their composition, frequent in normotensive patients, can lead to an increased affinity of this lipoprotein for arterial intimamedia components. It is proposed that this process could be an additional risk factor contributing to the deposition of LDL in the arterial wall."}
{"id": "PMID:184798", "title": "Serum lipid profiles in patients of myocardial infarction in the Chandigarh area (Northern India).", "content": "To study the incidence of hyperlipoproteinaemia in patients with myocardial infarction (MI) in the Chandigarh area, estimations of various lipids have been carried out in 83 patients. A serial study has been carried out in 31 patients. Serum lipoproteins and uric acid were also estimated. Results show an incidence of only 18% hypercholesterolaemia in patients with MI and 15% in normal subjects. Age-wise distribution of hypercholesterolaemia was slightly higher in 41-60 years old patients when compared with other age groups. No other abnormality in lipid profile was observed. Hyperuricaemia was not observed. These results, therefore, differ markedly from those of similar studies published from the western world.", "contents": "Serum lipid profiles in patients of myocardial infarction in the Chandigarh area (Northern India). To study the incidence of hyperlipoproteinaemia in patients with myocardial infarction (MI) in the Chandigarh area, estimations of various lipids have been carried out in 83 patients. A serial study has been carried out in 31 patients. Serum lipoproteins and uric acid were also estimated. Results show an incidence of only 18% hypercholesterolaemia in patients with MI and 15% in normal subjects. Age-wise distribution of hypercholesterolaemia was slightly higher in 41-60 years old patients when compared with other age groups. No other abnormality in lipid profile was observed. Hyperuricaemia was not observed. These results, therefore, differ markedly from those of similar studies published from the western world."}
{"id": "PMID:184799", "title": "Comparative studies on fatty acid synthesis in atherosclerotic and hypoxic human aorta.", "content": "The oxygen and glucose uptake, lactate formation, ATP/ADP and NADH/NAD ratios and incorporation of [14C]acetate and [14C]linolenic acid into lipids of early fatty streaks and more advanced complicated atherosclerotic lesions of human aorta were determined during aerobic and hypoxic incubation. Compared with grossly normal appearing sections of the aorta in intima and media preparations of early fatty streaks the oxygen uptake was increased while that in further developed atheroma was slightly diminished. Under aerobic incubation conditions the metabolic state of fatty streaks and atheroma was characterized by increased lactate formation, NADH/NAD ratio and incorporation of [14C]acetate and [14C]linolenic acid into the lipids, but by a lowered ATP/ADP ratio. More pronounced changes in these metabolic parameters were observed when the aortic tissue segments were incubated under hypoxic conditions. The analysis by argentation TLC of fatty acid methylesters derived from total lipids of aerobically incubated fatty streaks revealed an increased incorporation of [14C]acetate into the highly unsaturated long-chain fatty acids. In developed atherosclerotic lesions and in hypoxia the incorporation of radioacetate into the polyunsaturated fatty acids and the formation of 20:4 fatty acid from [14C]linolenic acid were, in contrast to the above finding, decreased while the synthesis of eicosatrienoic acid was increased. This finding suggests a block in the desaturation step of linoleic into 20:4 fatty acid in further developed atheroma and in hypoxia. In aerobically incubated atherosclerotic lesions and in hypoxia the palmitic acid was synthesized mainly by chain elongation while in grossly normal areas of the aorta at least part of this acid was synthesized de novo.", "contents": "Comparative studies on fatty acid synthesis in atherosclerotic and hypoxic human aorta. The oxygen and glucose uptake, lactate formation, ATP/ADP and NADH/NAD ratios and incorporation of [14C]acetate and [14C]linolenic acid into lipids of early fatty streaks and more advanced complicated atherosclerotic lesions of human aorta were determined during aerobic and hypoxic incubation. Compared with grossly normal appearing sections of the aorta in intima and media preparations of early fatty streaks the oxygen uptake was increased while that in further developed atheroma was slightly diminished. Under aerobic incubation conditions the metabolic state of fatty streaks and atheroma was characterized by increased lactate formation, NADH/NAD ratio and incorporation of [14C]acetate and [14C]linolenic acid into the lipids, but by a lowered ATP/ADP ratio. More pronounced changes in these metabolic parameters were observed when the aortic tissue segments were incubated under hypoxic conditions. The analysis by argentation TLC of fatty acid methylesters derived from total lipids of aerobically incubated fatty streaks revealed an increased incorporation of [14C]acetate into the highly unsaturated long-chain fatty acids. In developed atherosclerotic lesions and in hypoxia the incorporation of radioacetate into the polyunsaturated fatty acids and the formation of 20:4 fatty acid from [14C]linolenic acid were, in contrast to the above finding, decreased while the synthesis of eicosatrienoic acid was increased. This finding suggests a block in the desaturation step of linoleic into 20:4 fatty acid in further developed atheroma and in hypoxia. In aerobically incubated atherosclerotic lesions and in hypoxia the palmitic acid was synthesized mainly by chain elongation while in grossly normal areas of the aorta at least part of this acid was synthesized de novo."}
{"id": "PMID:184800", "title": "Increased collagen synthesis and the kinetic characteristics of prolyl hydroxylase in tissues of rabbits with experimental arteriosclerosis.", "content": "Increased aortic and liver prolyl hydroxylase activity has been suggested as an early biochemical indicator of the fibrotic changes which occur in rabbits with injury induced arteriosclerosis. Daily administration of epinephrine (0.025-0.050 mg/kg, i.v.) and thyroxine (0.050 mg/kg, i.p.) to rabbits for 3 weeks produced aortic fibrous plaques with a 4-fold increase in aortic prolyl hydroxylase and also a 5-fold increase in liver prolyl hydroxylase. Histopathologically, the livers of these rabbits show subcapsular areas of necrosis. When total prolyl hydroxylase related antigen was measured. the increase in liver prolyl hydroxylase activity accounted for only a small portion of the total prolyl hydroxylase antigen. However, in the aorta a majority of the increase in antigen is due to the increased amount of enzyme. DNA content per aorta was unchanged and RNA content increased in the aortic tissue of the arteriosclerotic rabbits. However DNA and RNA levels increased 60% in the livers of arteriosclerotic rabbits. In vitro incorporation of radioactively labeled proline into collagenase digestable protein was at least 2-fold greater in aorta and liver minces from arteriosclerotic rabbits. Michaelis--Menten kinetic parameters were obtained for the liver prolyl hydroxylase purified by affinity chromatography from arteriosclerotic rabbits. The Km for the enzyme from treated animals was not significantly different from control. However, the Vmax of the enzyme purified from diseased liver was 4-fold greater when compared to controls.", "contents": "Increased collagen synthesis and the kinetic characteristics of prolyl hydroxylase in tissues of rabbits with experimental arteriosclerosis. Increased aortic and liver prolyl hydroxylase activity has been suggested as an early biochemical indicator of the fibrotic changes which occur in rabbits with injury induced arteriosclerosis. Daily administration of epinephrine (0.025-0.050 mg/kg, i.v.) and thyroxine (0.050 mg/kg, i.p.) to rabbits for 3 weeks produced aortic fibrous plaques with a 4-fold increase in aortic prolyl hydroxylase and also a 5-fold increase in liver prolyl hydroxylase. Histopathologically, the livers of these rabbits show subcapsular areas of necrosis. When total prolyl hydroxylase related antigen was measured. the increase in liver prolyl hydroxylase activity accounted for only a small portion of the total prolyl hydroxylase antigen. However, in the aorta a majority of the increase in antigen is due to the increased amount of enzyme. DNA content per aorta was unchanged and RNA content increased in the aortic tissue of the arteriosclerotic rabbits. However DNA and RNA levels increased 60% in the livers of arteriosclerotic rabbits. In vitro incorporation of radioactively labeled proline into collagenase digestable protein was at least 2-fold greater in aorta and liver minces from arteriosclerotic rabbits. Michaelis--Menten kinetic parameters were obtained for the liver prolyl hydroxylase purified by affinity chromatography from arteriosclerotic rabbits. The Km for the enzyme from treated animals was not significantly different from control. However, the Vmax of the enzyme purified from diseased liver was 4-fold greater when compared to controls."}
{"id": "PMID:184801", "title": "Stimulation of proliferation in stationary primary cultures of monkey aortic smooth muscle cells. Part 2. Effect of varying concentrations of hyperlipemic serum and low density lipoproteins of varying dietary fat origins.", "content": "The outgrowth of medial explants of thoracic aorta from Rhesus monkeys has used to study the influence of hyperlipemic serum on cell proliferation. After 5-6 weeks of rapid growth in BME plus 10% normal serum, the cultures reach a stationary phase during which they show little mitotic activity. When it replaces 5% of the normal serum in the media, hyperlipemic serum induces another proliferative phase in the cultures, as measured by [3H1thymidine incorporation and increase in culture area. Low density lipoprotein (LDL) has the greatest stimulatory effect, while high density lipoprotein (HDL) has no effect. Hyperlipemic serum or its LDL still stimulates the cells even when diluted to achieve cholesterol levels comparable to the values with normal serum or LDL. Normal LDL has no effect, even when concentrated to increase its cholesterol level in the media. Thus it appears that hyperlipemic LDL has a stimulatory effect on arterial smooth muscle cells which does not depend on its higher lipid or cholesterol level.", "contents": "Stimulation of proliferation in stationary primary cultures of monkey aortic smooth muscle cells. Part 2. Effect of varying concentrations of hyperlipemic serum and low density lipoproteins of varying dietary fat origins. The outgrowth of medial explants of thoracic aorta from Rhesus monkeys has used to study the influence of hyperlipemic serum on cell proliferation. After 5-6 weeks of rapid growth in BME plus 10% normal serum, the cultures reach a stationary phase during which they show little mitotic activity. When it replaces 5% of the normal serum in the media, hyperlipemic serum induces another proliferative phase in the cultures, as measured by [3H1thymidine incorporation and increase in culture area. Low density lipoprotein (LDL) has the greatest stimulatory effect, while high density lipoprotein (HDL) has no effect. Hyperlipemic serum or its LDL still stimulates the cells even when diluted to achieve cholesterol levels comparable to the values with normal serum or LDL. Normal LDL has no effect, even when concentrated to increase its cholesterol level in the media. Thus it appears that hyperlipemic LDL has a stimulatory effect on arterial smooth muscle cells which does not depend on its higher lipid or cholesterol level."}
{"id": "PMID:184802", "title": "Clearing factor lipase (lipoprotein lipase) activator. A method for the measurement of the net activating ability of human sera.", "content": "The hydrolysis of an emulsified triglyceride substrate by clearing factor lipase (lipoprotein lipase) normally requires the presence of particular activating polypeptide species. These are present in serum, together with other inhibitory species, as part of the serum lipoproteins. The paper describes a method whereby the net activating ability of individual human sera may be measured routinely. In a normal population, this activating ability is shown to be correlated positively with the fasting serum triglyceride concentration. As the fasting triglyceride concentration increases, there is a rise in the proportion of the total activating ability that is associated with the very low density lipoproteins. A dietary fat load does not raise the total activating ability but does increase the proportion of the total that is associated with the serum lipoproteins of lowest density.", "contents": "Clearing factor lipase (lipoprotein lipase) activator. A method for the measurement of the net activating ability of human sera. The hydrolysis of an emulsified triglyceride substrate by clearing factor lipase (lipoprotein lipase) normally requires the presence of particular activating polypeptide species. These are present in serum, together with other inhibitory species, as part of the serum lipoproteins. The paper describes a method whereby the net activating ability of individual human sera may be measured routinely. In a normal population, this activating ability is shown to be correlated positively with the fasting serum triglyceride concentration. As the fasting triglyceride concentration increases, there is a rise in the proportion of the total activating ability that is associated with the very low density lipoproteins. A dietary fat load does not raise the total activating ability but does increase the proportion of the total that is associated with the serum lipoproteins of lowest density."}
{"id": "PMID:184805", "title": "Mesoridazine and human sleep.", "content": "1 Mesoridazine, a phenothiazine of short half-life, and potentially useful as an hypnotic, has here been investigated using volunteers of late middle age. 2 The electrophsiological recording of all-night sleep was studied in seven subjects for a 7-week period during which ther received mesoridazine (10 mg nightly) for 3 weeks. The drug reduced the frequency of transitions into wakefulness and stage 1 (drowsiness) and reduced the time spent in stage 1; there was a withdrawal rebound. Mesoridazine increased REM sleep above baseline levels and a rebound fall below baseline occurred on withdrawal. The drug did not alter the amount of stage 3 + 4 slow wave sleep. 3 Subjective self-ratings were assessed in a 6-week study of sixteen subjects. Sleep quality improved on mesoridazine (10 mg nightly) but there was diminution of zest and freshness 20 min after rising. Daytime concentration and anxiety were rated as not affected either by administration or withdrawal.", "contents": "Mesoridazine and human sleep. 1 Mesoridazine, a phenothiazine of short half-life, and potentially useful as an hypnotic, has here been investigated using volunteers of late middle age. 2 The electrophsiological recording of all-night sleep was studied in seven subjects for a 7-week period during which ther received mesoridazine (10 mg nightly) for 3 weeks. The drug reduced the frequency of transitions into wakefulness and stage 1 (drowsiness) and reduced the time spent in stage 1; there was a withdrawal rebound. Mesoridazine increased REM sleep above baseline levels and a rebound fall below baseline occurred on withdrawal. The drug did not alter the amount of stage 3 + 4 slow wave sleep. 3 Subjective self-ratings were assessed in a 6-week study of sixteen subjects. Sleep quality improved on mesoridazine (10 mg nightly) but there was diminution of zest and freshness 20 min after rising. Daytime concentration and anxiety were rated as not affected either by administration or withdrawal."}
{"id": "PMID:184806", "title": "Anxiety and sleep after fosazepam.", "content": "1 Six volunteers of mean age 59 years received placebo for week, then fosazepam (60 mg) nightly for 3 weeks, then placebo for 3 weeks. Subjective ratings and all-night electrophysiological recordings were made. 2 Fosazepam administration improved subjective sleep quality nut impaired feelings of morning vitality. Its withdrawal was associated with anxiety, impaired concentration and continuing impairment of morning vitality. Measured sleep duration increased on fosazepam, sleep was less broken, slow wave sleep stages 3 and 4 diminished in duration and so did REM sleep. 3 Despite the short-life of fosazepam some drug effects persisted for several days after withdrawal, suggesting action of a long half-life metabolite.", "contents": "Anxiety and sleep after fosazepam. 1 Six volunteers of mean age 59 years received placebo for week, then fosazepam (60 mg) nightly for 3 weeks, then placebo for 3 weeks. Subjective ratings and all-night electrophysiological recordings were made. 2 Fosazepam administration improved subjective sleep quality nut impaired feelings of morning vitality. Its withdrawal was associated with anxiety, impaired concentration and continuing impairment of morning vitality. Measured sleep duration increased on fosazepam, sleep was less broken, slow wave sleep stages 3 and 4 diminished in duration and so did REM sleep. 3 Despite the short-life of fosazepam some drug effects persisted for several days after withdrawal, suggesting action of a long half-life metabolite."}
{"id": "PMID:184808", "title": "Solid tumour models for the assessment of different treatment modalities: IV. the combined effects of radiation and 5-fluorouracil.", "content": "Neither radiation alone (375 to 1500 rad) nor5-fluorouracil (FU) alone (50-250 mg/kg) is sufficient to prevent an increase in the volume of the solid tumour model hepatoma 3924A. However, as little as 750 rad with 100 mg/kg FU can reduce the tumour below the volume at the time of treatment for as long as 14 days. A series of combined FU and radiation doses given every 11 days should then result in successively smaller tumour volumes until the tumour is eradicated. Changes in tumour volume were analysed by two different methods: (1) tumours in each treatment mode were grouped together and the average response to treatment determined, and (2) tumour volume changes in individual tumours were analyzed utilizing the chi2 technique, which fits the logarithmic tumour volume change with time to polynomials. This two-directional method of analysis has the advantage of permitting both an overview of the main effects of treatment via the averages, and at the same time a detailed examination of the mechanism by which these effects occur through the analysis of individual response. The results suggest that, in addition to concentrating on the cellular response immediately after therapy, greater emphasis should be placed on the kinetic changes of the tumour 1-3 weeks after single or multiple modality therapy. These findings demonstrate how the sequencing of single and/or combined treatment modalities may be investigated in order to detemine how best to obtain maximum effects of treatment on different types of tumours following recovery of the host from the previous treatment series.", "contents": "Solid tumour models for the assessment of different treatment modalities: IV. the combined effects of radiation and 5-fluorouracil. Neither radiation alone (375 to 1500 rad) nor5-fluorouracil (FU) alone (50-250 mg/kg) is sufficient to prevent an increase in the volume of the solid tumour model hepatoma 3924A. However, as little as 750 rad with 100 mg/kg FU can reduce the tumour below the volume at the time of treatment for as long as 14 days. A series of combined FU and radiation doses given every 11 days should then result in successively smaller tumour volumes until the tumour is eradicated. Changes in tumour volume were analysed by two different methods: (1) tumours in each treatment mode were grouped together and the average response to treatment determined, and (2) tumour volume changes in individual tumours were analyzed utilizing the chi2 technique, which fits the logarithmic tumour volume change with time to polynomials. This two-directional method of analysis has the advantage of permitting both an overview of the main effects of treatment via the averages, and at the same time a detailed examination of the mechanism by which these effects occur through the analysis of individual response. The results suggest that, in addition to concentrating on the cellular response immediately after therapy, greater emphasis should be placed on the kinetic changes of the tumour 1-3 weeks after single or multiple modality therapy. These findings demonstrate how the sequencing of single and/or combined treatment modalities may be investigated in order to detemine how best to obtain maximum effects of treatment on different types of tumours following recovery of the host from the previous treatment series."}
{"id": "PMID:184810", "title": "BCG treatment of malignant pleural effusions in the rat.", "content": "Intrapleurally injected cells of an ascitic rat tumour produced intrapleural effusions and solid pleural deposits. BCG, or its methanol extraction residue (MER) injected into the pleural space, suppressed tumour development and prolonged survival. Treatment was effective if given a few days before or after tumour injection. In contrast, active specific immunotherapy by repeated s.c. injection of viable or radiation-attenuated tumour cells in admixture with BCG was unsuccessful, and  did not improve the response to intrapleural BCG treatment.", "contents": "BCG treatment of malignant pleural effusions in the rat. Intrapleurally injected cells of an ascitic rat tumour produced intrapleural effusions and solid pleural deposits. BCG, or its methanol extraction residue (MER) injected into the pleural space, suppressed tumour development and prolonged survival. Treatment was effective if given a few days before or after tumour injection. In contrast, active specific immunotherapy by repeated s.c. injection of viable or radiation-attenuated tumour cells in admixture with BCG was unsuccessful, and  did not improve the response to intrapleural BCG treatment."}
{"id": "PMID:184811", "title": "Growth of a transplantable lymphoma and its modification in mice infected with the inducing virus.", "content": "The growth of a transplantable lymphoma was examined in normal mice and in mice previously infected with the lymphoma-inducing virus (ULV). Normal BALB/c mice respond to a footpad injection of X-irradiated lymphoma cells (ULMC) with popliteal lymph node (PLN) enlargement; mice previously infected with ULV do not. 106 viable ULMC injected into the footpads of ULV-infected mice grew progressively, and the animals died with disseminating malignant lymphoma. In contrast, this dose of cells injected into normal animals evoked strong host responses in the foot and draining lymph node, and no progressive growth of the lymphoma occurred. This increased susceptibility of the ULV-infected animals was also observed when ULMC were injected s.c. into the back or i.m. into the calf muscle, but not after s.c. injection of an unrelated 3-methylcholanthrene-induced sarcoma. Resistance to tumour growth after i.v. injection of ULMC is clearly ineffective, since 10 cells can grow and kill the animal, and in this case no increased susceptibility of ULV-infected animals was observed.", "contents": "Growth of a transplantable lymphoma and its modification in mice infected with the inducing virus. The growth of a transplantable lymphoma was examined in normal mice and in mice previously infected with the lymphoma-inducing virus (ULV). Normal BALB/c mice respond to a footpad injection of X-irradiated lymphoma cells (ULMC) with popliteal lymph node (PLN) enlargement; mice previously infected with ULV do not. 106 viable ULMC injected into the footpads of ULV-infected mice grew progressively, and the animals died with disseminating malignant lymphoma. In contrast, this dose of cells injected into normal animals evoked strong host responses in the foot and draining lymph node, and no progressive growth of the lymphoma occurred. This increased susceptibility of the ULV-infected animals was also observed when ULMC were injected s.c. into the back or i.m. into the calf muscle, but not after s.c. injection of an unrelated 3-methylcholanthrene-induced sarcoma. Resistance to tumour growth after i.v. injection of ULMC is clearly ineffective, since 10 cells can grow and kill the animal, and in this case no increased susceptibility of ULV-infected animals was observed."}
{"id": "PMID:184812", "title": "The induction of tumour cell adhesiveness and intercellular junctions by a glycoprotein of rat ascites hepatoma cell surface.", "content": "Rat ascites hepatoma AH109A cells (present as a free form in vivo) can aggregate and then develop well-defined tripartite junctional complexes, including intermediate junctions, desmosomes and focal tight junctions, on incubation with a glycoprotein separated from rat ascites hepatoma AH136B cells (forming cell islnds in vivo). The development of binding structures was strongly inhibited by actinomycin D. AH109A cells or rat ascites hepatoma YS cells (present as a free form in vivo) previously treated with the glycoprotein for 24 h, when inoculated i.p., proliferated as free cells in the ascitic fluid, like the untreated cells. AH109A cells actively proliferating in the skin do not form any junctional complexes. The reason for the failure of island formation by AH109A cells or YS cells in vivo is discussed.", "contents": "The induction of tumour cell adhesiveness and intercellular junctions by a glycoprotein of rat ascites hepatoma cell surface. Rat ascites hepatoma AH109A cells (present as a free form in vivo) can aggregate and then develop well-defined tripartite junctional complexes, including intermediate junctions, desmosomes and focal tight junctions, on incubation with a glycoprotein separated from rat ascites hepatoma AH136B cells (forming cell islnds in vivo). The development of binding structures was strongly inhibited by actinomycin D. AH109A cells or rat ascites hepatoma YS cells (present as a free form in vivo) previously treated with the glycoprotein for 24 h, when inoculated i.p., proliferated as free cells in the ascitic fluid, like the untreated cells. AH109A cells actively proliferating in the skin do not form any junctional complexes. The reason for the failure of island formation by AH109A cells or YS cells in vivo is discussed."}
{"id": "PMID:184815", "title": "The effect of collagenase on surface markers of human peripheral lymphocytes.", "content": "The effect of collagenase on the 'T' and 'B' markers of peripheral blood lymphocytes was studied in five healthy male blood donors. No significant difference between untreated and collagenase treated lymphocytes was found. Collagenase is recommended for use in liberating living cells from skin biopsy specimens.", "contents": "The effect of collagenase on surface markers of human peripheral lymphocytes. The effect of collagenase on the 'T' and 'B' markers of peripheral blood lymphocytes was studied in five healthy male blood donors. No significant difference between untreated and collagenase treated lymphocytes was found. Collagenase is recommended for use in liberating living cells from skin biopsy specimens."}
{"id": "PMID:184816", "title": "The effect of labour on ACTH and cortisol levels in amniotic fluid and maternal blood.", "content": "Levels of adrenocorticotrophic hormone (ACTH) and cortisol were measured in amniotic fluid during labour and in maternal blood during and after labour. There was a significant rise of maternal ACTH and cortisol levels during labour and a significant decrease after delivery in all 14 patients studied. There were no significant changes in amniotic fluid ACTH and cortisol levels during labour. The initial level of ACTH in amniotic fluid (162-7 pg/ml) was higher than that in maternal circulation (120-2 pg/ml). The correlation between maternal and amniotic fluid ACTH was not significant while the corresponding correlation for cortisol values was.", "contents": "The effect of labour on ACTH and cortisol levels in amniotic fluid and maternal blood. Levels of adrenocorticotrophic hormone (ACTH) and cortisol were measured in amniotic fluid during labour and in maternal blood during and after labour. There was a significant rise of maternal ACTH and cortisol levels during labour and a significant decrease after delivery in all 14 patients studied. There were no significant changes in amniotic fluid ACTH and cortisol levels during labour. The initial level of ACTH in amniotic fluid (162-7 pg/ml) was higher than that in maternal circulation (120-2 pg/ml). The correlation between maternal and amniotic fluid ACTH was not significant while the corresponding correlation for cortisol values was."}
{"id": "PMID:184817", "title": "Purification and properties of guanosine 5', 3'-polyphosphate synthetase from Bacillus brevis.", "content": "A ribosome-independent guanosine 5',3'-polyphosphate synthetase has been highly purified from Bacillus brevis (ATCC 8185). The enzyme has a molecular weight of 55,000, as measured by sucrose density gradient centrifugation. Like the ribosome-connected stringent factor of Escherichia coli, it catalyzes the synthesis of the guanosine 5', 3'-polyphosphates by a pyrophosphoryl transfer mechanism from adenosine triphosphate (ATP) to guanosine di- or triphosphates (GDP, GTP). It has an apparent Km of 0.14 mM for GDP and 0.77 mM for GTP, and is specific for the guanosine ribonucleotides as pyrophosphoryl acceptors. Several ATP analogues were tested for their ability to donate the pyrophosphoryl group. Mg2+ was required as a counter ion for the nucleotide substrate; however, an excess of Mg2+ was inhibitory. The property of the B. brevis enzyme is compared with the ribosome-linked enzyme of E. coli and an extracellular enzyme excreted by several types of Streptomyces reported upon recently.", "contents": "Purification and properties of guanosine 5', 3'-polyphosphate synthetase from Bacillus brevis. A ribosome-independent guanosine 5',3'-polyphosphate synthetase has been highly purified from Bacillus brevis (ATCC 8185). The enzyme has a molecular weight of 55,000, as measured by sucrose density gradient centrifugation. Like the ribosome-connected stringent factor of Escherichia coli, it catalyzes the synthesis of the guanosine 5', 3'-polyphosphates by a pyrophosphoryl transfer mechanism from adenosine triphosphate (ATP) to guanosine di- or triphosphates (GDP, GTP). It has an apparent Km of 0.14 mM for GDP and 0.77 mM for GTP, and is specific for the guanosine ribonucleotides as pyrophosphoryl acceptors. Several ATP analogues were tested for their ability to donate the pyrophosphoryl group. Mg2+ was required as a counter ion for the nucleotide substrate; however, an excess of Mg2+ was inhibitory. The property of the B. brevis enzyme is compared with the ribosome-linked enzyme of E. coli and an extracellular enzyme excreted by several types of Streptomyces reported upon recently."}
{"id": "PMID:184819", "title": "Enzymatic synthesis of (15s)-[15-3h]prostaglandins and their use in the development of a simple and sensitive assay for 15-hydroxyprostaglandin dehydrogenase.", "content": "The stereospecificity of swine renal NAD+-dependent 15-hydroxyprostaglandin dehydrogenase has been determined. It was found that the enzyme is a B-side specific dehydrogenase. (15S)-[15-3H]Prostaglandins were synthesized by stereospecific transfer of the tritium label of D-[1-3H]galactose to prostaglandins by coupling 15-hydroxyprostaglandin dehydrogenase with beta-D-galactose dehydrogenase, an enzyme of the same stereospecificity. A simple and sensitive assay for 15-hydroxyprostaglandin dehydrogenase was developed based on the stereospecific transfer of the tritium label of tritiated prostaglandins to glutamate by coupling 15-hydroxyprostaglandin dehydrogenase with glutamate dehydrogenase. The amount of prostaglandin oxidized is determined by the radioactivity of labeled glutamate present in the supernatant after charcoal precipitation of labeled prostaglandin. Concurrent assays with the present tritium release method and the thin-layer chromatography method indicated excellent correlation. The assay was employed to study some of the properties of swine renal 15-hydroxyprostaglandin dehydrogenase in crude extract and the distribution of enzyme activity in various tissues of rat. Enzyme activity was linear for the first 10 min studied and was nonlinear with increasing amounts of crude enzyme, indicating the possible presence of endogenous inhibitor(s). Apparent Km's for PGE2, PGF2alpha, and PGA2 were found to be 2.5, 12.5, and 3.9 muM, respectively. The distribution pattern indicated high levels of enzyme activity in gastrointestinal tract, lung, kidney, and spleen. The assay method may prove to be valuable for studying enzyme turnover and enzyme regulation by hormonal and pharmacological agents.", "contents": "Enzymatic synthesis of (15s)-[15-3h]prostaglandins and their use in the development of a simple and sensitive assay for 15-hydroxyprostaglandin dehydrogenase. The stereospecificity of swine renal NAD+-dependent 15-hydroxyprostaglandin dehydrogenase has been determined. It was found that the enzyme is a B-side specific dehydrogenase. (15S)-[15-3H]Prostaglandins were synthesized by stereospecific transfer of the tritium label of D-[1-3H]galactose to prostaglandins by coupling 15-hydroxyprostaglandin dehydrogenase with beta-D-galactose dehydrogenase, an enzyme of the same stereospecificity. A simple and sensitive assay for 15-hydroxyprostaglandin dehydrogenase was developed based on the stereospecific transfer of the tritium label of tritiated prostaglandins to glutamate by coupling 15-hydroxyprostaglandin dehydrogenase with glutamate dehydrogenase. The amount of prostaglandin oxidized is determined by the radioactivity of labeled glutamate present in the supernatant after charcoal precipitation of labeled prostaglandin. Concurrent assays with the present tritium release method and the thin-layer chromatography method indicated excellent correlation. The assay was employed to study some of the properties of swine renal 15-hydroxyprostaglandin dehydrogenase in crude extract and the distribution of enzyme activity in various tissues of rat. Enzyme activity was linear for the first 10 min studied and was nonlinear with increasing amounts of crude enzyme, indicating the possible presence of endogenous inhibitor(s). Apparent Km's for PGE2, PGF2alpha, and PGA2 were found to be 2.5, 12.5, and 3.9 muM, respectively. The distribution pattern indicated high levels of enzyme activity in gastrointestinal tract, lung, kidney, and spleen. The assay method may prove to be valuable for studying enzyme turnover and enzyme regulation by hormonal and pharmacological agents."}
{"id": "PMID:184820", "title": "Guanosine tetraphyosphate and its analogues. Chemical synthesis of guanosine 3',5'-dipyrophosphate, deoxyguanosine 3',5'-dipyrophosphate, guanosine 2',5'-bis(methylenediphosphonate), and guanosine 3',5'-bis(methylenediphosphonate).", "content": "A new procedure for the synthesis of the pyrophosphate bond has been employed in the preparation of nucleoside dipyrophosphates from nucleoside 3',5'-diphosphates. The method makes use of a powerful phosphorylating agent generated in a mixture of cyanoethyl phosphate, dicyclohexylcarbodiimide, and mesitylenesulfonyl chloride in order to avoid possible intramolecular reactions between the two phosphate groups on the sugar ring. That such reactions can readily occur was shown by the facile cyclization of deoxyguanosine 3',5'-diphosphate to P1,P2-deoxyguanosine 3',5'-cyclic pyrophosphate in the presence of dicyclohexylcarbodiimide alone. The phosphorylation reagent was initially tested in the conversion of deoxyguanosine 3',5'-diphosphate to the corresponding 3',5'-dipyrophosphate and was then used to phosphorylate 2'-O-(alpha-methoxyethyl)guanosine 3',5'-diphosphate, which had been prepared from 2'-O-(alpha-methoxyethyl)guanosine. In the latter case, the addition of the two beta phosphate groups was accomplished in 40% yield. Removal of the methoxyethyl group from the phosphorylated product gave guanosine 3',5'-dipyrophosphate, which was shown to be identical with guanosine tetraphosphate prepared enzymatically from a mixture of GDP and ATP. A modification of published procedures was also necessary to effect the synthesis of guanosine bis(methylenediphosphonate). Guanosine was treated with methylenediphosphonic acid and dicyclohexylcarbodiimide in the absence of added base. The product consisted of a mixture of guanosine 2',5' - and 3',5'-bis(methylenediphosphonate), which was resolved by anion-exchange chromatography. The 2',5' and 3',5' isomers are interconvertible at low pH, with the ultimate formation of an equilibrium mixture having a composition ratio of 2:3. The predominant constituent of this mixture has been unequivocally identified as the 3',5' isomer by synthesis from 2'-O-tetrahydropyranylguanosine.", "contents": "Guanosine tetraphyosphate and its analogues. Chemical synthesis of guanosine 3',5'-dipyrophosphate, deoxyguanosine 3',5'-dipyrophosphate, guanosine 2',5'-bis(methylenediphosphonate), and guanosine 3',5'-bis(methylenediphosphonate). A new procedure for the synthesis of the pyrophosphate bond has been employed in the preparation of nucleoside dipyrophosphates from nucleoside 3',5'-diphosphates. The method makes use of a powerful phosphorylating agent generated in a mixture of cyanoethyl phosphate, dicyclohexylcarbodiimide, and mesitylenesulfonyl chloride in order to avoid possible intramolecular reactions between the two phosphate groups on the sugar ring. That such reactions can readily occur was shown by the facile cyclization of deoxyguanosine 3',5'-diphosphate to P1,P2-deoxyguanosine 3',5'-cyclic pyrophosphate in the presence of dicyclohexylcarbodiimide alone. The phosphorylation reagent was initially tested in the conversion of deoxyguanosine 3',5'-diphosphate to the corresponding 3',5'-dipyrophosphate and was then used to phosphorylate 2'-O-(alpha-methoxyethyl)guanosine 3',5'-diphosphate, which had been prepared from 2'-O-(alpha-methoxyethyl)guanosine. In the latter case, the addition of the two beta phosphate groups was accomplished in 40% yield. Removal of the methoxyethyl group from the phosphorylated product gave guanosine 3',5'-dipyrophosphate, which was shown to be identical with guanosine tetraphosphate prepared enzymatically from a mixture of GDP and ATP. A modification of published procedures was also necessary to effect the synthesis of guanosine bis(methylenediphosphonate). Guanosine was treated with methylenediphosphonic acid and dicyclohexylcarbodiimide in the absence of added base. The product consisted of a mixture of guanosine 2',5' - and 3',5'-bis(methylenediphosphonate), which was resolved by anion-exchange chromatography. The 2',5' and 3',5' isomers are interconvertible at low pH, with the ultimate formation of an equilibrium mixture having a composition ratio of 2:3. The predominant constituent of this mixture has been unequivocally identified as the 3',5' isomer by synthesis from 2'-O-tetrahydropyranylguanosine."}
{"id": "PMID:184821", "title": "Purification and characterization of the DNA untwisting enzyme from rat liver.", "content": "The DNA untwisting enzyme has been purified approximately 300-fold from rat liver nuclei. The protein is greater than 90% pure as judged by sodium dodecyl sulfate-acrylamide gel electrophoresis. The native enzyme has a molecular weight between 64 000 and 68 000 and is composed of a single polypeptide chain. Evidence is presented that the protein can act catalytically. A trace amount of endonuclease activity associated with the most pure fraction could be a contaminant or it could be due to the action of the DNA untwisting enzyme itself.", "contents": "Purification and characterization of the DNA untwisting enzyme from rat liver. The DNA untwisting enzyme has been purified approximately 300-fold from rat liver nuclei. The protein is greater than 90% pure as judged by sodium dodecyl sulfate-acrylamide gel electrophoresis. The native enzyme has a molecular weight between 64 000 and 68 000 and is composed of a single polypeptide chain. Evidence is presented that the protein can act catalytically. A trace amount of endonuclease activity associated with the most pure fraction could be a contaminant or it could be due to the action of the DNA untwisting enzyme itself."}
{"id": "PMID:184822", "title": "Collagenase enzymes from Clostridium: characterization of individual enzymes.", "content": "Four collagenases have been purified to apparent homogeneity from extracts of Clostridium histolyticum and partially characterized. The four purified enzymes are devoid of hydrolytic activity against casein and the synthetic substrate, benzolyarginine naphthylamide, but all retain activity against native collagen. The enzymes are initially spearated by isoelectric focusing where three of the enzymes show distinct isoelectric points: collagenase I = 5.50, collagenase II = 5.65, and collagenases IIIa and IIIb = 5.90-6.00. Collagenases IIIa and IIIb can be subsequently separated on diethylaminoethylcellulose. The four purified enzymes show single bands upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Calibration of the molecular weights on the basis of migration distance shows a marked dependence on gel porosity. At high acrylamide concentration, collagenases I, II, and IIIa appear to converge to a limiting molecular weight congruent to 81 000, while collagenase IIIb has a distinctly lower value congruent to 72 000. The similarity between these molecular weight values and those derived from the sedimentation and diffusion coefficients of the native enzyme indicates that each collagenase is a single polypeptide chain. All of the collagenases have comparable catalytic activities against a series of natural and synthetic substrates and are immunologically cross-reactive. Although all four enzymes are evident upon initial electrofocusing of the crude extract, it is possible that the multiplicity of forms is, at least in part, a consequence of lysis following initial secretion from the cell.", "contents": "Collagenase enzymes from Clostridium: characterization of individual enzymes. Four collagenases have been purified to apparent homogeneity from extracts of Clostridium histolyticum and partially characterized. The four purified enzymes are devoid of hydrolytic activity against casein and the synthetic substrate, benzolyarginine naphthylamide, but all retain activity against native collagen. The enzymes are initially spearated by isoelectric focusing where three of the enzymes show distinct isoelectric points: collagenase I = 5.50, collagenase II = 5.65, and collagenases IIIa and IIIb = 5.90-6.00. Collagenases IIIa and IIIb can be subsequently separated on diethylaminoethylcellulose. The four purified enzymes show single bands upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Calibration of the molecular weights on the basis of migration distance shows a marked dependence on gel porosity. At high acrylamide concentration, collagenases I, II, and IIIa appear to converge to a limiting molecular weight congruent to 81 000, while collagenase IIIb has a distinctly lower value congruent to 72 000. The similarity between these molecular weight values and those derived from the sedimentation and diffusion coefficients of the native enzyme indicates that each collagenase is a single polypeptide chain. All of the collagenases have comparable catalytic activities against a series of natural and synthetic substrates and are immunologically cross-reactive. Although all four enzymes are evident upon initial electrofocusing of the crude extract, it is possible that the multiplicity of forms is, at least in part, a consequence of lysis following initial secretion from the cell."}
{"id": "PMID:184823", "title": "Hydrolysis of triphosphoinositides by a soluble fraction of Crithidia fasciculata.", "content": "Homogenates of Crithidia fasciculata (a species of Trypanosomidae) were shown to contain a phosphatase (EC 3.1.3.36) and a phosphodiesterase (EC 3.1.4.11) which hydrolyse triphosphoinositides. Approximately 30% of the diesterase and most of the phosphatase are present in the soluble fraction. The triphosphoinositide phosphatase is specifically dependent upon Mg(2+) and is stable to storage with or without freezing. The triphosphoinositide phosphodiesterase requires Ca(2+) and is inactivated during storage. Both activities are maximal in the presence of cetyltrimethylammonium bromide and require protection or reactivation by GSH or dithiothreitol. Unlike similar mammalian enzymes the protozoal triphosphoinositide phosphatase does not hydrolyse diphosphoinositides. The two enzymes may be separated by (NH4)2SO4 fractionation and gel filtration on Sephadex G-200.", "contents": "Hydrolysis of triphosphoinositides by a soluble fraction of Crithidia fasciculata. Homogenates of Crithidia fasciculata (a species of Trypanosomidae) were shown to contain a phosphatase (EC 3.1.3.36) and a phosphodiesterase (EC 3.1.4.11) which hydrolyse triphosphoinositides. Approximately 30% of the diesterase and most of the phosphatase are present in the soluble fraction. The triphosphoinositide phosphatase is specifically dependent upon Mg(2+) and is stable to storage with or without freezing. The triphosphoinositide phosphodiesterase requires Ca(2+) and is inactivated during storage. Both activities are maximal in the presence of cetyltrimethylammonium bromide and require protection or reactivation by GSH or dithiothreitol. Unlike similar mammalian enzymes the protozoal triphosphoinositide phosphatase does not hydrolyse diphosphoinositides. The two enzymes may be separated by (NH4)2SO4 fractionation and gel filtration on Sephadex G-200."}
{"id": "PMID:184824", "title": "Localization of neutral glycosphingolipids in human plasma.", "content": "1. The localization of the neutral glycosphingolipids glucosylceramide, lactosylceramide, trihexosylceramide and globoside in human plasma was investigated. Glycosphingolipids were isolated and analysed by gas-liquid chromatography. 2. After Sephadex gel chromatography of human plasma, about 75% of the glycosphingolipids were found in the fraction containing most of the lipoproteins. 3. After fractionation of the lipoproteins by ionic precipitation, 15-25% of each glycosphingolipid was found in the very low-density lipoprotein + chylomicron fraction, 30-45% in the low density lipoprotein fraction and 40-50% in the high density lipoprotein fraction. 4. After fractionation of lipoproteins by density-gradient ultracentrifugation, 15% of each glycosphingolipid was found in the very low-density lipoprotein + chylomicron fraction and 85% in the low density and high density lipoprotein fractions. No glycosphingolipids could be detected in the ultracentrifugal residue which contains the bulk of the albumin.", "contents": "Localization of neutral glycosphingolipids in human plasma. 1. The localization of the neutral glycosphingolipids glucosylceramide, lactosylceramide, trihexosylceramide and globoside in human plasma was investigated. Glycosphingolipids were isolated and analysed by gas-liquid chromatography. 2. After Sephadex gel chromatography of human plasma, about 75% of the glycosphingolipids were found in the fraction containing most of the lipoproteins. 3. After fractionation of the lipoproteins by ionic precipitation, 15-25% of each glycosphingolipid was found in the very low-density lipoprotein + chylomicron fraction, 30-45% in the low density lipoprotein fraction and 40-50% in the high density lipoprotein fraction. 4. After fractionation of lipoproteins by density-gradient ultracentrifugation, 15% of each glycosphingolipid was found in the very low-density lipoprotein + chylomicron fraction and 85% in the low density and high density lipoprotein fractions. No glycosphingolipids could be detected in the ultracentrifugal residue which contains the bulk of the albumin."}
{"id": "PMID:184825", "title": "Selective utilization of endogenous unsaturated phosphatidylcholines and diacylglycerols by cholinephosphotransferase of mouse lung microsomes.", "content": "In the presence of CMP, cholinephosphotransferase of mouse lung microsomes catalyzes the conversion of endogenous phosphatidylcholines into 1,2-diacyl-sn-glycerols and CDPcholine. 2. In this conversion cholinephosphotransferase shows a distinct preference for those molecular species of phosphatidylcholine which contain an unsaturated fatty acid. The enzyme hardly utilizes endogenous depalmitoylglycerophosphocholine as a substrate. 3. Membrane-bound 1,2-diacyl-sn-glycerols were also prepared by treatment of mouse lung microsomes with a pure phospholipase C from Bacillus cereus. These 1,2-diacyl-sn-glycerols were subsequently utilized as substrate by cholinephosphotransferase in the formation of phosphatidylcholine. In the latter reaction, cholinephosphotransferase exhibited a pronounced preference for unsaturated 1,2-diacyl-sn-glycerols and hardly utilized the endogenous 1,2-depalmitoyl-sn-glycerol. 4. The low affinity of cholinephosphotransferase for either dipalmitoylglycerophosphocholine or 1,2-dip", "contents": "Selective utilization of endogenous unsaturated phosphatidylcholines and diacylglycerols by cholinephosphotransferase of mouse lung microsomes. In the presence of CMP, cholinephosphotransferase of mouse lung microsomes catalyzes the conversion of endogenous phosphatidylcholines into 1,2-diacyl-sn-glycerols and CDPcholine. 2. In this conversion cholinephosphotransferase shows a distinct preference for those molecular species of phosphatidylcholine which contain an unsaturated fatty acid. The enzyme hardly utilizes endogenous depalmitoylglycerophosphocholine as a substrate. 3. Membrane-bound 1,2-diacyl-sn-glycerols were also prepared by treatment of mouse lung microsomes with a pure phospholipase C from Bacillus cereus. These 1,2-diacyl-sn-glycerols were subsequently utilized as substrate by cholinephosphotransferase in the formation of phosphatidylcholine. In the latter reaction, cholinephosphotransferase exhibited a pronounced preference for unsaturated 1,2-diacyl-sn-glycerols and hardly utilized the endogenous 1,2-depalmitoyl-sn-glycerol. 4. The low affinity of cholinephosphotransferase for either dipalmitoylglycerophosphocholine or 1,2-dip"}
{"id": "PMID:184826", "title": "Activity of cholinephosphotransferase, lysolecithin: lysolecithin acyltransferase and lysolecithin acyltransferase in the developing mouse lung.", "content": "1. The present study presents the activity profiles of cholinephosphotransferase, lysolecithin:lysolecithin acyltransferase and lysolecithin acyltransferase at different stages of development of the mouse lung. 2. The specific activity of cholinephosphotransferase, a key enzyme in the de novo synthesis of phosphatidylcholine, increases during the later stages of fetal development until it reaches a maximal value at a gestational age of 17 days, i.e. 2 days before term. Thereafter, the activity of the enzyme declines again until around term. 2. The specific activity of lysolecithin:lysolecithin acyltransferase which catalyzes the transesterification between two molecules of 1-acyl-sn-glycero-3-phosphocholine, appears to be much lower than that of cholinephosphotransferase at gestational ages below 18 days. However, around day 18, the specific activity of lysolecithin:lysolecithin acyltransferase increases dramatically until it almost equals the maximal activity of cholinephosphotransferase measured on day 17. 4. The specific activity of lysolecithin acyltransferase, which catalyzes the direct acylation of 1-acyl-sn-glycero-3-phosphocholine, does not change significantly during the prenatal development and is lower than that of either lysolecithin:lysolecithin acyltransferase or cholinephosphotransferase at all stages of development. 5. These results are discussed in view of the possible role of these enzymes in the biosynthesis of pulmonary 1,2-dipalmitoyl-sn-glycero-3-phosphocholine.", "contents": "Activity of cholinephosphotransferase, lysolecithin: lysolecithin acyltransferase and lysolecithin acyltransferase in the developing mouse lung. 1. The present study presents the activity profiles of cholinephosphotransferase, lysolecithin:lysolecithin acyltransferase and lysolecithin acyltransferase at different stages of development of the mouse lung. 2. The specific activity of cholinephosphotransferase, a key enzyme in the de novo synthesis of phosphatidylcholine, increases during the later stages of fetal development until it reaches a maximal value at a gestational age of 17 days, i.e. 2 days before term. Thereafter, the activity of the enzyme declines again until around term. 2. The specific activity of lysolecithin:lysolecithin acyltransferase which catalyzes the transesterification between two molecules of 1-acyl-sn-glycero-3-phosphocholine, appears to be much lower than that of cholinephosphotransferase at gestational ages below 18 days. However, around day 18, the specific activity of lysolecithin:lysolecithin acyltransferase increases dramatically until it almost equals the maximal activity of cholinephosphotransferase measured on day 17. 4. The specific activity of lysolecithin acyltransferase, which catalyzes the direct acylation of 1-acyl-sn-glycero-3-phosphocholine, does not change significantly during the prenatal development and is lower than that of either lysolecithin:lysolecithin acyltransferase or cholinephosphotransferase at all stages of development. 5. These results are discussed in view of the possible role of these enzymes in the biosynthesis of pulmonary 1,2-dipalmitoyl-sn-glycero-3-phosphocholine."}
{"id": "PMID:184827", "title": "High resolution preparative column chromatographic system for gangliosides using DEAE-Sephadex and a new porus silica, Iatrobeads.", "content": "A new high-resolution preparative column chromatographic system was developed for efficient and rapid isolation of ganglioside molecular species. The system involved a combination of ion-exchange and adsorption chromatographies using DEAE-Sephadex A-25 and the newly developed, totally porous silica spheres, Iatrobeads. Using this system the brain gangliosides, GM1, GD1a, GD1b and GT1 were obtained in high purity and in milligram amounts, in a relatively short time, by simple procedures. The presence of a number of unidentified molecular species of gangliosides, which are present only in small amounts, was also demonstrated.", "contents": "High resolution preparative column chromatographic system for gangliosides using DEAE-Sephadex and a new porus silica, Iatrobeads. A new high-resolution preparative column chromatographic system was developed for efficient and rapid isolation of ganglioside molecular species. The system involved a combination of ion-exchange and adsorption chromatographies using DEAE-Sephadex A-25 and the newly developed, totally porous silica spheres, Iatrobeads. Using this system the brain gangliosides, GM1, GD1a, GD1b and GT1 were obtained in high purity and in milligram amounts, in a relatively short time, by simple procedures. The presence of a number of unidentified molecular species of gangliosides, which are present only in small amounts, was also demonstrated."}
{"id": "PMID:184829", "title": "A rapid assay method of collagenase activity using 14C-labeled soluble collagen as substrate.", "content": "A rapid assay method for vertebrate collagenase (EC 3.4.24.3) activity has been developed using 14C-labeled soluble collagen as substrate. The method is based on the incubation of collagen with enzyme in the presence of glucose to prevent collagen fibril formation followed by selective extraction of the enzyme digestion products into dioxane at a final concentration of 50%. The rate of reaction was about 10 times higher than that obtained by the conventional method using reconstituted collagen fibrils as substrate and the relationship between enzyme activity and concentration was linear over a wider range. When the method was applied to the assay of human granulocyte collagenase, the results showed good correlation with those obtained by the conventional gel method.", "contents": "A rapid assay method of collagenase activity using 14C-labeled soluble collagen as substrate. A rapid assay method for vertebrate collagenase (EC 3.4.24.3) activity has been developed using 14C-labeled soluble collagen as substrate. The method is based on the incubation of collagen with enzyme in the presence of glucose to prevent collagen fibril formation followed by selective extraction of the enzyme digestion products into dioxane at a final concentration of 50%. The rate of reaction was about 10 times higher than that obtained by the conventional method using reconstituted collagen fibrils as substrate and the relationship between enzyme activity and concentration was linear over a wider range. When the method was applied to the assay of human granulocyte collagenase, the results showed good correlation with those obtained by the conventional gel method."}
{"id": "PMID:184830", "title": "Particulate carbonic anhydrase in homogenates of human kidney.", "content": "About 2% of human kidney carbonic anhydrase (carbonate hydro-lyase, EC 4.2.1.1) has been found in particulate fractions. Its distribution in the particulate fractions obtained by differential centrifugation suggests that it may be concentrated in the brush border. The particulate enzyme is like red cell carbonic anhydrace C in its susceptibility to inhibition by anions. Particulate carbonic anhydrase is firmly bound to the membrane and is not released by incubation at pH 10.6 and 37 degrees C or by addition of Triton X-100 or deoxycholate. In 10% Triton X-100 at pH 11.3 and 37 degrees C, the particulate enzyme is inactivated with a half time of about 20 min, and this is at least an order of magnitude slower than the inactivation of soluble enzymes in the presence or absence of membranes. The soluble enzymes are inactivated within a few minutes at 25 degrees C in 3-4% sodium dodecyl sulfate, but the particulate enzyme is relatively stable under those conditions, and its half-time of inactivation at 14 degrees C with a detergent-protein ratio of 25 was about 24 h. Gel filtration with Ultragel AcA-44 in sodium dodecyl sulfate indicates that the membrane carbonic anhydrase has a molecular weight of less than 66 000, so its stability is not due to association with large membrane fragments or vesicles. These results suggest that the membrane enzyme may be a different isozyme than the soluble carbonic anhydrases. Although present in relatively small amounts, its localization on the membrane could give it functional significance.", "contents": "Particulate carbonic anhydrase in homogenates of human kidney. About 2% of human kidney carbonic anhydrase (carbonate hydro-lyase, EC 4.2.1.1) has been found in particulate fractions. Its distribution in the particulate fractions obtained by differential centrifugation suggests that it may be concentrated in the brush border. The particulate enzyme is like red cell carbonic anhydrace C in its susceptibility to inhibition by anions. Particulate carbonic anhydrase is firmly bound to the membrane and is not released by incubation at pH 10.6 and 37 degrees C or by addition of Triton X-100 or deoxycholate. In 10% Triton X-100 at pH 11.3 and 37 degrees C, the particulate enzyme is inactivated with a half time of about 20 min, and this is at least an order of magnitude slower than the inactivation of soluble enzymes in the presence or absence of membranes. The soluble enzymes are inactivated within a few minutes at 25 degrees C in 3-4% sodium dodecyl sulfate, but the particulate enzyme is relatively stable under those conditions, and its half-time of inactivation at 14 degrees C with a detergent-protein ratio of 25 was about 24 h. Gel filtration with Ultragel AcA-44 in sodium dodecyl sulfate indicates that the membrane carbonic anhydrase has a molecular weight of less than 66 000, so its stability is not due to association with large membrane fragments or vesicles. These results suggest that the membrane enzyme may be a different isozyme than the soluble carbonic anhydrases. Although present in relatively small amounts, its localization on the membrane could give it functional significance."}
{"id": "PMID:184831", "title": "Cyclic AMP-stimulated phosphorylation of bovine tracheal smooth muscle contractile and non-contractile proteins.", "content": "1. Various proteins isolated from bovine tracheal smooth muscle were examined as phosphate acceptor substrates for a cyclic AMP-dependent protein kinase isolated from the same tissue. A fraction prepared in a manner similar to that of skeletal muscle troponin was the best substrate of the presumptive contractile proteins isolate. Actomyosin and tropomyosin were relatively poor substrates. 2. An assay was developed for the rapid detection in a large number of samples of the muscle specific substrate for the protein kinase on which we reported previously. 3. Using this assay, the muscle specific substrate found in bovine tracheal smooth muscle was partially purified resulting in a preparation which when resolved by polyacrylamide gel electrophoresis showed a single peak of 32P incorporated, and which could be further characterized. 4. Our findings suggest that the substrate contains a protein subunit of molecular weight 19 000, which can be phosphorylated at serine and threonine residues, in the presence of cyclic AMP and protein kinase. The phosphate is in a covalent ester linkage with these residues. 5. A phosphoprotein phosphatase was isolated from the bovine tracheal smooth muscle. 6. Bovine tracheal smooth muscle contains cyclic AMP dependent protein kinase and phosphoprotein phospahatase activity as well as the muscle specific substrate, suggesting that these elements may be part of a mechanism which regulates smooth muscle tone.", "contents": "Cyclic AMP-stimulated phosphorylation of bovine tracheal smooth muscle contractile and non-contractile proteins. 1. Various proteins isolated from bovine tracheal smooth muscle were examined as phosphate acceptor substrates for a cyclic AMP-dependent protein kinase isolated from the same tissue. A fraction prepared in a manner similar to that of skeletal muscle troponin was the best substrate of the presumptive contractile proteins isolate. Actomyosin and tropomyosin were relatively poor substrates. 2. An assay was developed for the rapid detection in a large number of samples of the muscle specific substrate for the protein kinase on which we reported previously. 3. Using this assay, the muscle specific substrate found in bovine tracheal smooth muscle was partially purified resulting in a preparation which when resolved by polyacrylamide gel electrophoresis showed a single peak of 32P incorporated, and which could be further characterized. 4. Our findings suggest that the substrate contains a protein subunit of molecular weight 19 000, which can be phosphorylated at serine and threonine residues, in the presence of cyclic AMP and protein kinase. The phosphate is in a covalent ester linkage with these residues. 5. A phosphoprotein phosphatase was isolated from the bovine tracheal smooth muscle. 6. Bovine tracheal smooth muscle contains cyclic AMP dependent protein kinase and phosphoprotein phospahatase activity as well as the muscle specific substrate, suggesting that these elements may be part of a mechanism which regulates smooth muscle tone."}
{"id": "PMID:184832", "title": "Binding of nitroxide stearate spin labels to bovine serum albumin.", "content": "1. 12-Nitroxide stearate binds to bovine serum albumin at about four independent and equivalent binding sites with an association constant of about 10(6) M-1. The binding at these high affinity binding sites is significantly reduced by addition of unlabeled stearate. These data suggest that nitroxide stearates probe the high affinity binding sites for long-chain fatty acids. 2. Qualitative analyses of the ESR spectra of 5-, 12- and 16-nitroxide stearate bound to bovine serum albumin and measurements of the interaction of these compounds so bound with ferricyanide ion provide a rough description of the binding site as follows: the polar headgroup of the spin-labeled fatty acid is rigidly fixed, but fairly accessible to paramagnetic ions. The middle part of the hydrocarbon chain of bound stearate spin label also is rigidly fixed but differs in being shielded from the solvent, presumably by a hydrophobic cleft. The methyl terminus shows greater motion, appearing to move within a narrow cone, and also appears to be somewhat accessible to paramagnetic ions.", "contents": "Binding of nitroxide stearate spin labels to bovine serum albumin. 1. 12-Nitroxide stearate binds to bovine serum albumin at about four independent and equivalent binding sites with an association constant of about 10(6) M-1. The binding at these high affinity binding sites is significantly reduced by addition of unlabeled stearate. These data suggest that nitroxide stearates probe the high affinity binding sites for long-chain fatty acids. 2. Qualitative analyses of the ESR spectra of 5-, 12- and 16-nitroxide stearate bound to bovine serum albumin and measurements of the interaction of these compounds so bound with ferricyanide ion provide a rough description of the binding site as follows: the polar headgroup of the spin-labeled fatty acid is rigidly fixed, but fairly accessible to paramagnetic ions. The middle part of the hydrocarbon chain of bound stearate spin label also is rigidly fixed but differs in being shielded from the solvent, presumably by a hydrophobic cleft. The methyl terminus shows greater motion, appearing to move within a narrow cone, and also appears to be somewhat accessible to paramagnetic ions."}
{"id": "PMID:184833", "title": "Effects of guanidine hydrochloride on human plasma high density lipoproteins.", "content": "Denaturation of human plasma high density lipoproteins during ultracentrifugation in guanidine-HCl is characterized by: dissociation of apoA-I, in the range of 2-3 M guanidine-HCl, and dissociation of apoA-I and apoA-II in 5-6 M guanidine-HCl. Denaturation of high density lipoprotein species, during a sequence of timed exposure to guanidine-HCl followed first by removal of the denaturant by dialysis and then by ultracentrifugation, is characterized by:dissociation of lipid-poor apoA-I, which follows a time course similar to denaturation-related changes in reported spectroscopic parameters; and apparent formation of lipoprotein aggregation products depleted in apoA-I and relatively enriched in apoA-II. These studies indicate differential properties of the major apoproteins in stabilizing high density lipoprotein structure and characterize a mode of lipoprotein transformation and degradation which apparently results from apoprotein dissociation coupled with aggregation of denatured lipoprote species.", "contents": "Effects of guanidine hydrochloride on human plasma high density lipoproteins. Denaturation of human plasma high density lipoproteins during ultracentrifugation in guanidine-HCl is characterized by: dissociation of apoA-I, in the range of 2-3 M guanidine-HCl, and dissociation of apoA-I and apoA-II in 5-6 M guanidine-HCl. Denaturation of high density lipoprotein species, during a sequence of timed exposure to guanidine-HCl followed first by removal of the denaturant by dialysis and then by ultracentrifugation, is characterized by:dissociation of lipid-poor apoA-I, which follows a time course similar to denaturation-related changes in reported spectroscopic parameters; and apparent formation of lipoprotein aggregation products depleted in apoA-I and relatively enriched in apoA-II. These studies indicate differential properties of the major apoproteins in stabilizing high density lipoprotein structure and characterize a mode of lipoprotein transformation and degradation which apparently results from apoprotein dissociation coupled with aggregation of denatured lipoprote species."}
{"id": "PMID:184834", "title": "Haem accessibility in cytochrome P-450 from rabbit liver. A proton magnetic relaxation study by stereochemical probes.", "content": "Cytochrome P-450 was solubilized from phenobarbital induced rabbit liver and purified by affinity chromatography. The longitudinal proton magnetic relaxation rates of this ferric, low-spin sample (as confirmed by ESR) in 20% glycerol aqueous solution are very large compared with low-spin methaemoglobin and myoglobin derivatives. Similarly high rates were measured in a deuterated solution using the aliphatic protons of glycerol as stereochemical markers, which strongly suggests that the haem iron in cytochrome P-450 is much more accessible to the solvent than in harmoglobin or myoglobin. Type I substate (Spasman) produced small but significant increases in NMR rates both in the H2O and in the 2H2O solution, while binding of aniline (Type II substrate) doubled the rates.", "contents": "Haem accessibility in cytochrome P-450 from rabbit liver. A proton magnetic relaxation study by stereochemical probes. Cytochrome P-450 was solubilized from phenobarbital induced rabbit liver and purified by affinity chromatography. The longitudinal proton magnetic relaxation rates of this ferric, low-spin sample (as confirmed by ESR) in 20% glycerol aqueous solution are very large compared with low-spin methaemoglobin and myoglobin derivatives. Similarly high rates were measured in a deuterated solution using the aliphatic protons of glycerol as stereochemical markers, which strongly suggests that the haem iron in cytochrome P-450 is much more accessible to the solvent than in harmoglobin or myoglobin. Type I substate (Spasman) produced small but significant increases in NMR rates both in the H2O and in the 2H2O solution, while binding of aniline (Type II substrate) doubled the rates."}
{"id": "PMID:184835", "title": "Radioimmunoassay of apolipoprotein A-I of rat serum.", "content": "A double antibody radioimmunoassay technique was developed for quantification of apolipoprotein A-I, the major apoprotein of rat high density lipoprotein. Apo A-I was labeled with 125I by the chloramine-T method. 125I-labeled apo A-I had the same electrophoretic mobility as unlabeled apo A-I and more than 80% of the 125I was precipitated by rabbit anti apo A-I antibodies. The assay is sensitive at the level of 0.5-5 ng, and has intraassay and interassay coefficients of variation of 4.5 and 6.5% respectively. The specificity of the assay was established by competitive displacement of 125I-labeled apo A-I from its antibody by apo A-I and lipoproteins containing apo A-I, but not by rat albumin and other apoproteins. Immunoreactivity of high density lipoprotein and serum was only about 35% of that of their delipidated forms when Veronal buffer was used as a diluent. Inclusion of 5 mM sodium decyl sulfate in the incubation mixture brought out reactivity equivalent to that found after delipidation. Completeness of the reaction was verified by comparison with the amount of apo A-I in chromatographic fractions of the total apoprotein of high density lipoprotein. Content (weight %, mean values +/- S.D.) of immunoassayable apo A-I was: 62.3 +/- 5.9 in high density lipoprotein; 1.7 +/- 0.3 in low density lipoprotein; 0.09 +/- 0.03 in very low density lipoprotein and 25.0 +/- 5.0 in lymp chylomicrons. Concentration in whole serum was 51.4 +/- 8.9 mg/dl and 33.6 +/- 4.1 mg/dl for female and male rats, respectively (p less than 0.002), equivalent to the sex difference in concentration of high density lipoprotein. 95% of the apo A-I in serum was in high density lipoprotein, 5% in proteins of d greater than 1.21 g/ml and less than 1% in lipoproteins of d less than 1.063 g/ml.", "contents": "Radioimmunoassay of apolipoprotein A-I of rat serum. A double antibody radioimmunoassay technique was developed for quantification of apolipoprotein A-I, the major apoprotein of rat high density lipoprotein. Apo A-I was labeled with 125I by the chloramine-T method. 125I-labeled apo A-I had the same electrophoretic mobility as unlabeled apo A-I and more than 80% of the 125I was precipitated by rabbit anti apo A-I antibodies. The assay is sensitive at the level of 0.5-5 ng, and has intraassay and interassay coefficients of variation of 4.5 and 6.5% respectively. The specificity of the assay was established by competitive displacement of 125I-labeled apo A-I from its antibody by apo A-I and lipoproteins containing apo A-I, but not by rat albumin and other apoproteins. Immunoreactivity of high density lipoprotein and serum was only about 35% of that of their delipidated forms when Veronal buffer was used as a diluent. Inclusion of 5 mM sodium decyl sulfate in the incubation mixture brought out reactivity equivalent to that found after delipidation. Completeness of the reaction was verified by comparison with the amount of apo A-I in chromatographic fractions of the total apoprotein of high density lipoprotein. Content (weight %, mean values +/- S.D.) of immunoassayable apo A-I was: 62.3 +/- 5.9 in high density lipoprotein; 1.7 +/- 0.3 in low density lipoprotein; 0.09 +/- 0.03 in very low density lipoprotein and 25.0 +/- 5.0 in lymp chylomicrons. Concentration in whole serum was 51.4 +/- 8.9 mg/dl and 33.6 +/- 4.1 mg/dl for female and male rats, respectively (p less than 0.002), equivalent to the sex difference in concentration of high density lipoprotein. 95% of the apo A-I in serum was in high density lipoprotein, 5% in proteins of d greater than 1.21 g/ml and less than 1% in lipoproteins of d less than 1.063 g/ml."}
{"id": "PMID:184836", "title": "Repair replication in cultured normal and transformed human fibroblasts.", "content": "Repair replication in response to ultraviolet irradiation has been studied in normal human diploid fibroblast cultures, W138, and an SV40 transformant, VA13. Quantitative comparisons have been made using the combined isotopic and density labeling method for assaying repair replication. We find no significant difference in the amount of repair replication performed its dose response, or the time course between growing and confluent W138 cells, early passage and senescent cells, or normal W138 cells and the transformed VA13 cells. When [3H]dThd was employed as the isotopic label in the presence of a 30-200 fold excess of unlabelled BrdUrd, apparent differences in repair replication were seen between W138 cells shortly after subcultivation and cells which had been allowed to reach confluence. These differences were the same over a wide dose range and regardless of the passage number of the cells, but could be influenced by using different serum lots. The differences were not seen, however, when [3H]BrdUrd provided the isotopic label; thus they reflect either impurities in the [3H]dThd or a slight discrimination by some cellular process.", "contents": "Repair replication in cultured normal and transformed human fibroblasts. Repair replication in response to ultraviolet irradiation has been studied in normal human diploid fibroblast cultures, W138, and an SV40 transformant, VA13. Quantitative comparisons have been made using the combined isotopic and density labeling method for assaying repair replication. We find no significant difference in the amount of repair replication performed its dose response, or the time course between growing and confluent W138 cells, early passage and senescent cells, or normal W138 cells and the transformed VA13 cells. When [3H]dThd was employed as the isotopic label in the presence of a 30-200 fold excess of unlabelled BrdUrd, apparent differences in repair replication were seen between W138 cells shortly after subcultivation and cells which had been allowed to reach confluence. These differences were the same over a wide dose range and regardless of the passage number of the cells, but could be influenced by using different serum lots. The differences were not seen, however, when [3H]BrdUrd provided the isotopic label; thus they reflect either impurities in the [3H]dThd or a slight discrimination by some cellular process."}
{"id": "PMID:184837", "title": "Caffeine, cyclic AMP and postreplication repair of mammalian cell DNA.", "content": "The methylxanthines, caffeine and theophylline, inhibit postreplication repair of DNA in mammalian cells. Because they also inhibit cyclic AMP phosphodiesterase, it was thought that there might be some connection between concentrations of cyclic AMP and postreplication repair. We tested this possibility by performing DNA sedimentation experiments with a cyclic AMP-resistant mouse lymphoma cell mutant and its wild-type counterpart. The results show that there is no connection between cellular cyclic AMP concentrations and the rate of postreplication repair. Therefore, it is more likely that caffeine and theophylline inhibit postreplication repair by some other means, such as by binding to DNA.", "contents": "Caffeine, cyclic AMP and postreplication repair of mammalian cell DNA. The methylxanthines, caffeine and theophylline, inhibit postreplication repair of DNA in mammalian cells. Because they also inhibit cyclic AMP phosphodiesterase, it was thought that there might be some connection between concentrations of cyclic AMP and postreplication repair. We tested this possibility by performing DNA sedimentation experiments with a cyclic AMP-resistant mouse lymphoma cell mutant and its wild-type counterpart. The results show that there is no connection between cellular cyclic AMP concentrations and the rate of postreplication repair. Therefore, it is more likely that caffeine and theophylline inhibit postreplication repair by some other means, such as by binding to DNA."}
{"id": "PMID:184838", "title": "Induction of alpha type DNA polymerases in human cytomegalovirus-infected WI-38 cells.", "content": "Productive infection of WI-38 cells with human cytomegalovirus (HCMV) induced the increase in the activity of DNA polymerases as well as the synthesis of viral and cellular DNA. Sedimentation analyses in sucrose gradients of high ionic strength showed that the HCMV infection caused marked increase in the activity of alpha-type polymerases (resolved into alpha1, 8 S, and alpha 2, 6 S, in the present experiments), while the infection little affected the level of beta-type polymerase (about 3.5 S) activity in both the nuclei and cytoplasm. Such increase in alpha-type polymerases was also observed when DNA synthesis in WI-38 cells was enhanced by SV40 infection or by an increased concentration of serum in medium. Phosphonacetate, which selectively blocked the synthesis of HCMV DNA, did not significantly affect the HCMV-mediated induction of DNA polymerases. However, phosphonoacetate added in the reaction mixture for DNA polymerase assay inhibited the activity of the HCMV-induced polyperase alpha, but not of the polymerases alpha2 and beta. These results support the idea that alpha-type polymerases are involved in the replicative synthesis of cellular and viral DNA.", "contents": "Induction of alpha type DNA polymerases in human cytomegalovirus-infected WI-38 cells. Productive infection of WI-38 cells with human cytomegalovirus (HCMV) induced the increase in the activity of DNA polymerases as well as the synthesis of viral and cellular DNA. Sedimentation analyses in sucrose gradients of high ionic strength showed that the HCMV infection caused marked increase in the activity of alpha-type polymerases (resolved into alpha1, 8 S, and alpha 2, 6 S, in the present experiments), while the infection little affected the level of beta-type polymerase (about 3.5 S) activity in both the nuclei and cytoplasm. Such increase in alpha-type polymerases was also observed when DNA synthesis in WI-38 cells was enhanced by SV40 infection or by an increased concentration of serum in medium. Phosphonacetate, which selectively blocked the synthesis of HCMV DNA, did not significantly affect the HCMV-mediated induction of DNA polymerases. However, phosphonoacetate added in the reaction mixture for DNA polymerase assay inhibited the activity of the HCMV-induced polyperase alpha, but not of the polymerases alpha2 and beta. These results support the idea that alpha-type polymerases are involved in the replicative synthesis of cellular and viral DNA."}
{"id": "PMID:184839", "title": "The study of rous sarcoma virus-transformed baby hamster kidney cells using fluorescent probes.", "content": "The fluorescent probes pyrene, pyrene butyric acid and N-phenyl 1-naphthylamine have been used to investigate the changes that accompany  in vitro transformation of a baby hamster kidney cell line using Rous sarcoma virus. The fluorescent probes which reside in the membrane were used to compare the changes in microviscosity and polarity of the membranes of normal cells with two transformed cell lines. The spectrofluorimetric data indicate that following transformation the probe N-phenyl 1-naphthylamine resides in a more polar environment. However, using the probe pyrene, the yield of excimer indicates decreased mobility of this probe in the membrane of transformed cells. The data also indicate differences between the two transformed cell lines. Laser photolysis was used to study the lifetime of the pyrene probes and the quenching of the pyrene fluorescence in the membrane by several different quenching molecules. The data indicate differences between the three cell lines and suggest that transformation decreases movement within the membrane.", "contents": "The study of rous sarcoma virus-transformed baby hamster kidney cells using fluorescent probes. The fluorescent probes pyrene, pyrene butyric acid and N-phenyl 1-naphthylamine have been used to investigate the changes that accompany  in vitro transformation of a baby hamster kidney cell line using Rous sarcoma virus. The fluorescent probes which reside in the membrane were used to compare the changes in microviscosity and polarity of the membranes of normal cells with two transformed cell lines. The spectrofluorimetric data indicate that following transformation the probe N-phenyl 1-naphthylamine resides in a more polar environment. However, using the probe pyrene, the yield of excimer indicates decreased mobility of this probe in the membrane of transformed cells. The data also indicate differences between the two transformed cell lines. Laser photolysis was used to study the lifetime of the pyrene probes and the quenching of the pyrene fluorescence in the membrane by several different quenching molecules. The data indicate differences between the three cell lines and suggest that transformation decreases movement within the membrane."}
{"id": "PMID:184840", "title": "Preparation and properties of vesicles of a purified myelin hydrophobic protein and phospholipid. A spin label study.", "content": "Lipophilin, a hydrophobic protein purified from the proteolipid of normal hupid and protein in 2-chloro-ethanol followed by dialysis against buffer. This method resulted in homogeneous incorporation of the protein into lipid vesicles as judged by sedimentation on a sucrose gradient and freeze fracture electreter and the freeze fracture faces contained intramembrane particles. The effect of lipophilin on the organization of the lipid was studied by use of spin label probes. Two distinct components were present in the spectrum of fatty acid spin labels in the lipid-protein vesicles. One was immobilized presumably due to the presence of boundary lipid around the protein and the second component waicles and probably due to a lamellar phase but with a slightly greater order parameter. Lipophilin was found to increase the order parameter linearly with increasing concentration of protein incorporated into the vesicles. However, the phase transition temperature as measured from the 2,2,6,6-tetramethyl piperidine-1-oxyl (TEMPO) solubility parameter was unchanged.", "contents": "Preparation and properties of vesicles of a purified myelin hydrophobic protein and phospholipid. A spin label study. Lipophilin, a hydrophobic protein purified from the proteolipid of normal hupid and protein in 2-chloro-ethanol followed by dialysis against buffer. This method resulted in homogeneous incorporation of the protein into lipid vesicles as judged by sedimentation on a sucrose gradient and freeze fracture electreter and the freeze fracture faces contained intramembrane particles. The effect of lipophilin on the organization of the lipid was studied by use of spin label probes. Two distinct components were present in the spectrum of fatty acid spin labels in the lipid-protein vesicles. One was immobilized presumably due to the presence of boundary lipid around the protein and the second component waicles and probably due to a lamellar phase but with a slightly greater order parameter. Lipophilin was found to increase the order parameter linearly with increasing concentration of protein incorporated into the vesicles. However, the phase transition temperature as measured from the 2,2,6,6-tetramethyl piperidine-1-oxyl (TEMPO) solubility parameter was unchanged."}
{"id": "PMID:184841", "title": "Hormonal control of uterine contraction. Characterization od cyclic AMP-dependent membrane properties in the myometrium.", "content": "A mitochondria-free membrane fraction prepared from rat myometrium accumulated 45Ca2+ in the presence of oxalic acid and ATP. The rate of transport of Ca2+ into the membranous vesicles was increased by greater than 50% in the presence of 3',5'-cyclic AMP, but not by 2',3'-cyclic AMP or 5'AMP. Membrane ATPase activity was stimulated by Mg2+; slight additional stimulation was obtained in the presence of Na+ and K+ but not in the presence of Ca+2. Despite the cyclic AMP sensitivity of membrane ATPase activity, the absence of any effect of inhibitors of Ca2+-transport suggest it has little to do with Ca2+ accumulation by the membranes. Cyclic AMP-induced increase in Ca2+-transport and membrane ATPase activity was duplicated in vivo by incubating uteri in 10(-4)M isoproterenol prior to membrane isolation. Isoproterenol has been previously shown to increase myometrial cyclic AMP levels, and changes in Ca2+-transport by cell membranes in relation to intracellular cyclic AMP levels may be the mechanism through which hormones modulate uterine contractility.", "contents": "Hormonal control of uterine contraction. Characterization od cyclic AMP-dependent membrane properties in the myometrium. A mitochondria-free membrane fraction prepared from rat myometrium accumulated 45Ca2+ in the presence of oxalic acid and ATP. The rate of transport of Ca2+ into the membranous vesicles was increased by greater than 50% in the presence of 3',5'-cyclic AMP, but not by 2',3'-cyclic AMP or 5'AMP. Membrane ATPase activity was stimulated by Mg2+; slight additional stimulation was obtained in the presence of Na+ and K+ but not in the presence of Ca+2. Despite the cyclic AMP sensitivity of membrane ATPase activity, the absence of any effect of inhibitors of Ca2+-transport suggest it has little to do with Ca2+ accumulation by the membranes. Cyclic AMP-induced increase in Ca2+-transport and membrane ATPase activity was duplicated in vivo by incubating uteri in 10(-4)M isoproterenol prior to membrane isolation. Isoproterenol has been previously shown to increase myometrial cyclic AMP levels, and changes in Ca2+-transport by cell membranes in relation to intracellular cyclic AMP levels may be the mechanism through which hormones modulate uterine contractility."}
{"id": "PMID:184842", "title": "Oxidation and reduction of membrane-bound cytochrome c in Hemophilus parainfluenzae. Reaction with oxygen, hydrogen peroxide and nitrate.", "content": "Cytochromes of the a-, b-, c- and d-type become reduced when intact cells of Hemophilus parainfluenzae have become anaerobic following respiration with substrates such as formate or succinate, as shown previously (J. Biol. Chem. (1970) 254, 5096-5100). In the presence of formate after depletion of O2, there is an unusual two-step time course of reduction of the membrane-bound cytochrome c. The proportion of the cytochrome c which is reduced during the second stage is oxidizable by either nitrate or H2O2 and is reduced again when the nitrate or H2O2 have been depleted. We conclude that the observed two-stage reduction of cytochrome c results from the presence of an oxidant, probably H2O2, produced by reaction of formate dehydrogenase with O2. This was shown by the effects of cyanide, catalase and O2. In addition, no evidence for the production of the oxidant is seen when succinate is the substrate oxidized. Although measurements of absorption spectra indicated only one species of cytochrome c, kinetic evidence is presented for some separation of the cytochrome c into more than one electron transport pathway.", "contents": "Oxidation and reduction of membrane-bound cytochrome c in Hemophilus parainfluenzae. Reaction with oxygen, hydrogen peroxide and nitrate. Cytochromes of the a-, b-, c- and d-type become reduced when intact cells of Hemophilus parainfluenzae have become anaerobic following respiration with substrates such as formate or succinate, as shown previously (J. Biol. Chem. (1970) 254, 5096-5100). In the presence of formate after depletion of O2, there is an unusual two-step time course of reduction of the membrane-bound cytochrome c. The proportion of the cytochrome c which is reduced during the second stage is oxidizable by either nitrate or H2O2 and is reduced again when the nitrate or H2O2 have been depleted. We conclude that the observed two-stage reduction of cytochrome c results from the presence of an oxidant, probably H2O2, produced by reaction of formate dehydrogenase with O2. This was shown by the effects of cyanide, catalase and O2. In addition, no evidence for the production of the oxidant is seen when succinate is the substrate oxidized. Although measurements of absorption spectra indicated only one species of cytochrome c, kinetic evidence is presented for some separation of the cytochrome c into more than one electron transport pathway."}
{"id": "PMID:184843", "title": "Electron paramagnetic resonance studies of cytochrome P-450 and adrenal ferredoxin in single whole rat adrenal glands. Effect of corticotropin.", "content": "Low and high spin ferric cytochrome P-450 and reduced adrenal ferredoxin (adrenodoxin) have been directly studied by EPR techniques in whole rat adrenal glands. The spectra obtained correspond closely to those obtained from sub-cellular fractions except in the case of low spin ferric cytochrome P-450, where there are differences in the shape of the g = 2.41 line. The relative magnitudes of these peaks in anaerobic and aerobic rapidly frozen adrenals from control and corticotropin stimulated hypophysectomised rats were used to investigate the control and rate limiting steps in adrenal steroid biosynthesis via cytochrome P-450. All adrenals showed a close to maximal level of reduced adrenodoxin and aerobic and anaerobic glands from control rats and aerobic glands from corticotropin stimulated rats showed similar quantities of low spin ferric cytochrome P-450. On anaerobiosis the quantity of low spin ferric cytochrome in adrenals from corticotropin stimulated rats dropped to 30--40% of the aerobic level. Treatment of the rats with cycloheximide prior to administration of corticotropin prevented these changes. Approximately 0.4% of the total cytochrome P-450 was high spin ferric in control adrenals and in aerobic stimulated adrenals this rose to approximately to 0.6%. These results demonstrate that association of substrate with cytochrome P-450 is the rate limiting step in adrenal steroidogenesis via cytochrome P-450. It is suggested on the basis of these and mitochondrial optical and EPR experiments that the limiting step being observed is cholesterol binding to cholesterol side chain cleavage cytochrome P-450, and that the rate of this association is stimulated by corticotropin.", "contents": "Electron paramagnetic resonance studies of cytochrome P-450 and adrenal ferredoxin in single whole rat adrenal glands. Effect of corticotropin. Low and high spin ferric cytochrome P-450 and reduced adrenal ferredoxin (adrenodoxin) have been directly studied by EPR techniques in whole rat adrenal glands. The spectra obtained correspond closely to those obtained from sub-cellular fractions except in the case of low spin ferric cytochrome P-450, where there are differences in the shape of the g = 2.41 line. The relative magnitudes of these peaks in anaerobic and aerobic rapidly frozen adrenals from control and corticotropin stimulated hypophysectomised rats were used to investigate the control and rate limiting steps in adrenal steroid biosynthesis via cytochrome P-450. All adrenals showed a close to maximal level of reduced adrenodoxin and aerobic and anaerobic glands from control rats and aerobic glands from corticotropin stimulated rats showed similar quantities of low spin ferric cytochrome P-450. On anaerobiosis the quantity of low spin ferric cytochrome in adrenals from corticotropin stimulated rats dropped to 30--40% of the aerobic level. Treatment of the rats with cycloheximide prior to administration of corticotropin prevented these changes. Approximately 0.4% of the total cytochrome P-450 was high spin ferric in control adrenals and in aerobic stimulated adrenals this rose to approximately to 0.6%. These results demonstrate that association of substrate with cytochrome P-450 is the rate limiting step in adrenal steroidogenesis via cytochrome P-450. It is suggested on the basis of these and mitochondrial optical and EPR experiments that the limiting step being observed is cholesterol binding to cholesterol side chain cleavage cytochrome P-450, and that the rate of this association is stimulated by corticotropin."}
{"id": "PMID:184846", "title": "[Hydrocarbon metabolism in a marine bacterium].", "content": "The marine bacterium L.16.1 (Alcaligenes sp.) grows preferentially on alkanes (C10 to C18) with a very high growth yield (98 per cent); optimal growth depends strictly on the presence of a well-defined NaCl concentration (100 mM). Our strain is constitutive for the enzymatic systems responsible for the oxidation of alkanes to fatty acids, i.e. NADH-dependent hydroxylase, alcohol and aldehyde dehydrogenases, the latter of which located at the cytoplasmic membrane level. The aerobic oxidation of primary alcohols by particulate extracts prepared in the presence of 400 mM NaCl is NAD+-dependent (Km = 0.082 mM, Vmax = 238 with decanol). With extracts prepared in the absence of NaCl, Vmax undergoes a very strong decrease. On the contrary , the NAD+ (P)+-dependent oxidation of aldehydes is carried out anaerobically by the same extracts irrespective of the presence or the absence of added Na+ in the solutions used for the preparation of these extracts. A possible explanation for our results could be that Na+ acts on the enzymatic systems for which the maintenance of the membrane integrity is essential. This interpretation is consistent with the slowing down of the growth speed accompanying the decrease of NaCl concentration in the growth medium. With regard to alcohol and aldehyde-dehydrogenases, it is noteworthy that these enzymes behave like similar enzymatic activities induced by alkanes in other microorganisms.", "contents": "[Hydrocarbon metabolism in a marine bacterium]. The marine bacterium L.16.1 (Alcaligenes sp.) grows preferentially on alkanes (C10 to C18) with a very high growth yield (98 per cent); optimal growth depends strictly on the presence of a well-defined NaCl concentration (100 mM). Our strain is constitutive for the enzymatic systems responsible for the oxidation of alkanes to fatty acids, i.e. NADH-dependent hydroxylase, alcohol and aldehyde dehydrogenases, the latter of which located at the cytoplasmic membrane level. The aerobic oxidation of primary alcohols by particulate extracts prepared in the presence of 400 mM NaCl is NAD+-dependent (Km = 0.082 mM, Vmax = 238 with decanol). With extracts prepared in the absence of NaCl, Vmax undergoes a very strong decrease. On the contrary , the NAD+ (P)+-dependent oxidation of aldehydes is carried out anaerobically by the same extracts irrespective of the presence or the absence of added Na+ in the solutions used for the preparation of these extracts. A possible explanation for our results could be that Na+ acts on the enzymatic systems for which the maintenance of the membrane integrity is essential. This interpretation is consistent with the slowing down of the growth speed accompanying the decrease of NaCl concentration in the growth medium. With regard to alcohol and aldehyde-dehydrogenases, it is noteworthy that these enzymes behave like similar enzymatic activities induced by alkanes in other microorganisms."}
{"id": "PMID:184847", "title": "In vivo study of free and esterified cholesterol turnover in various tissues of the rat.", "content": "Rats were infused for 3.5 to 10 hrs with either red cells or plasma previously labelled in vivo by [3H]-cholesterol. Cholesterol specific radioactivities were measured in plasma, HDL, LDL and VLDL, and various tissues. Red cell infusions led to a higher labelling of free than of esterified cholesterol in the plasma of infused rats. The opposite situation was observed following plasma infusion. Comparison of free and esterified cholesterol specific radioactivities in each tissue showed that esterified cholesterol was transferred from plasma to all the tissues, except the adrenals. Study of the ratios of cholesterol specific radioactivities from one experimental group to the other in each tissue, made it possible to demonstrate clearly the occurence of hydrolysis within all the studied tissues except 5 of them where its existence remains uncertain (lung, heart, kidney, tendon, muscle) and of esterification in 3 tissues (adrenal, liver lung). In addition, ratios of cholesterol radioactivities (free/ester) were found to be identical in plasma and in 4 tissues, where neither hydrolysis nor esterification were detected (heart, muscle, kidney, tendon). This finding is an argument in favor of a simultaneous transport of free and esterified cholesterol from plasma into these 4 tissues and suggests that the entire lipoprotein particles can penetrate these tissues, with no specificity of one special class. In adrenal, unlike all other tissues: 1) the turnover of esterified cholesterol was achieved mostly by hydrolysis and esterification in situ; 2) a preferential lipoprotein class (LDL) was responsible for the transport of free cholesterol from the plasma.", "contents": "In vivo study of free and esterified cholesterol turnover in various tissues of the rat. Rats were infused for 3.5 to 10 hrs with either red cells or plasma previously labelled in vivo by [3H]-cholesterol. Cholesterol specific radioactivities were measured in plasma, HDL, LDL and VLDL, and various tissues. Red cell infusions led to a higher labelling of free than of esterified cholesterol in the plasma of infused rats. The opposite situation was observed following plasma infusion. Comparison of free and esterified cholesterol specific radioactivities in each tissue showed that esterified cholesterol was transferred from plasma to all the tissues, except the adrenals. Study of the ratios of cholesterol specific radioactivities from one experimental group to the other in each tissue, made it possible to demonstrate clearly the occurence of hydrolysis within all the studied tissues except 5 of them where its existence remains uncertain (lung, heart, kidney, tendon, muscle) and of esterification in 3 tissues (adrenal, liver lung). In addition, ratios of cholesterol radioactivities (free/ester) were found to be identical in plasma and in 4 tissues, where neither hydrolysis nor esterification were detected (heart, muscle, kidney, tendon). This finding is an argument in favor of a simultaneous transport of free and esterified cholesterol from plasma into these 4 tissues and suggests that the entire lipoprotein particles can penetrate these tissues, with no specificity of one special class. In adrenal, unlike all other tissues: 1) the turnover of esterified cholesterol was achieved mostly by hydrolysis and esterification in situ; 2) a preferential lipoprotein class (LDL) was responsible for the transport of free cholesterol from the plasma."}
{"id": "PMID:184851", "title": "[Kinetic properties and heat resistance of the peritoneal leukocyte myeloperoxidase of white mice].", "content": "The dependence of the myeloperoxidase-catalyzed reaction in the concentration of the enzyme and that of both substrates (hydrogenperoxide and o-dianizidine) was investigated. The substrates--velocity curves appeared non-hyperbolic, an inhibitory effect was registered for both substrates. Hill coefficient with a varying value was employed to characterize the deviation of the curves from Michaelis--Menten hyperbolas apparently caused by the interaction of non-identical subunits composing the enzyme molecule. The effect of the preincubation temperature on the enzyme activity and the kinetics of thermoinactivation of the enzyme are analysed, the purified enzyme preparation being more thermostable than the crude one.", "contents": "[Kinetic properties and heat resistance of the peritoneal leukocyte myeloperoxidase of white mice]. The dependence of the myeloperoxidase-catalyzed reaction in the concentration of the enzyme and that of both substrates (hydrogenperoxide and o-dianizidine) was investigated. The substrates--velocity curves appeared non-hyperbolic, an inhibitory effect was registered for both substrates. Hill coefficient with a varying value was employed to characterize the deviation of the curves from Michaelis--Menten hyperbolas apparently caused by the interaction of non-identical subunits composing the enzyme molecule. The effect of the preincubation temperature on the enzyme activity and the kinetics of thermoinactivation of the enzyme are analysed, the purified enzyme preparation being more thermostable than the crude one."}
{"id": "PMID:184852", "title": "[Participation of 5'-deoxyadenosyl-B12 in regulating methylation of tRNA].", "content": "The effects of different forms of cobalamines on the activities of tRNA-methylases of Zajdela ascite hepatoma were studied. Of six cobamides studied 5'-deoxyadenosyl-B12 and factor B containing as a ligand HSO3 in the concentrations of 2.4-10(-5) and 4.8-10(-5) M inhibited the tRNA-methylase activity by  21% and 15% correspondingly. The inhibitory effect of 5'-deoxyadenosyl-B12 is probably dependent on the adenosyl part of the molecule. 5'deoxyadenosyl-B12 exerted a selective effect of Zajdela ascite hepatoma tRNA-methylases, inhibiting largely the activity of 5-methyl cytosine methylase during the methylation of the E. coli K12W6 tRNA and yeast tRNA1 Val.", "contents": "[Participation of 5'-deoxyadenosyl-B12 in regulating methylation of tRNA]. The effects of different forms of cobalamines on the activities of tRNA-methylases of Zajdela ascite hepatoma were studied. Of six cobamides studied 5'-deoxyadenosyl-B12 and factor B containing as a ligand HSO3 in the concentrations of 2.4-10(-5) and 4.8-10(-5) M inhibited the tRNA-methylase activity by  21% and 15% correspondingly. The inhibitory effect of 5'-deoxyadenosyl-B12 is probably dependent on the adenosyl part of the molecule. 5'deoxyadenosyl-B12 exerted a selective effect of Zajdela ascite hepatoma tRNA-methylases, inhibiting largely the activity of 5-methyl cytosine methylase during the methylation of the E. coli K12W6 tRNA and yeast tRNA1 Val."}
{"id": "PMID:184853", "title": "[Hysteresis, alternative stationary states and auto-oscillations in an open futile cycle one of the reactions of which is substrate inhibited].", "content": "In connection with the problem of regulation of futile (energy-dissipating) cycles in cell metabolism, a kinetic model has been investigated of an open cycle S1 (see article) S2, in which one of the enzymes (E-) is inhibited by the excess of its substrate S2. The quasi-stationary net velocity of the utilization of substrate S1 in the cycle as a function of its concentration is shown to be of a hysteretic character. Owing to this the alternative stationary states and self-oscillations may occur in the cycle. Under certain conditions the transition from one alternative state to another may reverse the direction of the net flux of conversion from S1 to S2 or vice versa. The self-oscillations are associated with a periodical change in the net flux direction. It is suggested the participation of glycogen (starch) in the self-oscillatory mechanism of the futile cycle formed by the phosphofructokinase and fructose bisphosphatase reactions may give rise to oscillations with the period of 10(3)-10(4) min, which may serve as the basis for the cell clock.", "contents": "[Hysteresis, alternative stationary states and auto-oscillations in an open futile cycle one of the reactions of which is substrate inhibited]. In connection with the problem of regulation of futile (energy-dissipating) cycles in cell metabolism, a kinetic model has been investigated of an open cycle S1 (see article) S2, in which one of the enzymes (E-) is inhibited by the excess of its substrate S2. The quasi-stationary net velocity of the utilization of substrate S1 in the cycle as a function of its concentration is shown to be of a hysteretic character. Owing to this the alternative stationary states and self-oscillations may occur in the cycle. Under certain conditions the transition from one alternative state to another may reverse the direction of the net flux of conversion from S1 to S2 or vice versa. The self-oscillations are associated with a periodical change in the net flux direction. It is suggested the participation of glycogen (starch) in the self-oscillatory mechanism of the futile cycle formed by the phosphofructokinase and fructose bisphosphatase reactions may give rise to oscillations with the period of 10(3)-10(4) min, which may serve as the basis for the cell clock."}
{"id": "PMID:184854", "title": "[Cytochrome oxidase of rat liver nuclear membranes and its interaction with mitochondrial cytochrome oxidase].", "content": "The percent of mitochondrial protein contamination in nuclei decreased 10-fold (from 18 to 1.8%) under purification of protein-labelled mitochondria before their introduction into nuclei-free homogenate, cytochromoxidase activity being unchanged. Thus, cytochromoxidase activity of nuclei does not correlate with the amount of nuclei-adsorbed mitochondrial protein, which demonstrates the presence of nuclear cytochromoxidase independent on mitochondrial protein. Radioactivity of protein-labelled mitochondria is proportially distributed between globuline, deoxyribonucleoprotein, acid and residual nuclear proteins, as it is shown under fractionation of nuclei isolated from protein-labeled mitochondria containing homogenate. The comparison of mitochondrial protein contamination of nuclear membranes and their possible contamination with cytochromoxidase and suecinate-cytochrome-c-reducatase activities revealed that cytochromoxidase activity of nuclear membranes is twice higher and succinate-cytochrome-c-reductase activity is considerably lower than it can be referred to mitochondrial protein contamination. The ratio of cytochrome-c-oxidase and succinate-cytochrome-c-reductase activities in isolated nuclear membranes is 4-7 times as high as that in mitochondrial membranes under the same isolation procedure. The data obtained make possible to consider the cytochromoxidase activity of nuclear membranes to be really nuclear enzyme, and not a contominant of nucleipreparation with mitochondrial membranes.", "contents": "[Cytochrome oxidase of rat liver nuclear membranes and its interaction with mitochondrial cytochrome oxidase]. The percent of mitochondrial protein contamination in nuclei decreased 10-fold (from 18 to 1.8%) under purification of protein-labelled mitochondria before their introduction into nuclei-free homogenate, cytochromoxidase activity being unchanged. Thus, cytochromoxidase activity of nuclei does not correlate with the amount of nuclei-adsorbed mitochondrial protein, which demonstrates the presence of nuclear cytochromoxidase independent on mitochondrial protein. Radioactivity of protein-labelled mitochondria is proportially distributed between globuline, deoxyribonucleoprotein, acid and residual nuclear proteins, as it is shown under fractionation of nuclei isolated from protein-labeled mitochondria containing homogenate. The comparison of mitochondrial protein contamination of nuclear membranes and their possible contamination with cytochromoxidase and suecinate-cytochrome-c-reducatase activities revealed that cytochromoxidase activity of nuclear membranes is twice higher and succinate-cytochrome-c-reductase activity is considerably lower than it can be referred to mitochondrial protein contamination. The ratio of cytochrome-c-oxidase and succinate-cytochrome-c-reductase activities in isolated nuclear membranes is 4-7 times as high as that in mitochondrial membranes under the same isolation procedure. The data obtained make possible to consider the cytochromoxidase activity of nuclear membranes to be really nuclear enzyme, and not a contominant of nucleipreparation with mitochondrial membranes."}
{"id": "PMID:184855", "title": "[Concentration of components of the adenylate system in heavy and light fractions of the sarcoplasmic reticulum of skeletal muscles and sensitivity of these fractions to the effects of imidazole-containing compounds and caffeine].", "content": "Fragments of sarcoplasmic reticulum from rabbit sceletal muscles sedimented within the range from 2000 g to 8000 g (heavy fraction) and 8000 g to 40000 g (light fraction) and washed with 0.6 M KCl, were practically free of adenylatecyclase activity. Phosphodiesterase cAMP was not found in the light fraction, while its activity in the heavy fraction was 500 pmol of cAMP/min per mg of protein. Both fractions contain bound cAMP (1-2 pmol/mg of protein) and specific sites of cAMP binding, the binding constant being approximately 10(6)M-1. The number of binding sites is 60 pmol/mg of protein for the heavy and 30 pmol/mg of protein for the light fractions. The level of phosphodiesterase activity in the heavy fraction correlates with its sensitivity to imidazole, anserine and caffeine. Imidazole and anserine increase in 1.5-1.8 times the value of Ca2+/ATP in the heavy fraction and produce no effect on Ca2+ transport by the light fraction. Caffeine decreases almost twice the Ca2+/ATP value in the heavy fraction and has practically no effect on Ca2+ absorption by enzymes of the light reticulum fraction. Imidazole and anserine activate membrane-bound phosphodiesterase, while caffeine inhibits it. It is suggested that structural rearrangements of membrane-bound phosphodiesterase under the effect of caffeine, imidazole and anserine are responsible for changes in the efficiency of Ca2+ transport by fragments of the heavy reticulum fractions.", "contents": "[Concentration of components of the adenylate system in heavy and light fractions of the sarcoplasmic reticulum of skeletal muscles and sensitivity of these fractions to the effects of imidazole-containing compounds and caffeine]. Fragments of sarcoplasmic reticulum from rabbit sceletal muscles sedimented within the range from 2000 g to 8000 g (heavy fraction) and 8000 g to 40000 g (light fraction) and washed with 0.6 M KCl, were practically free of adenylatecyclase activity. Phosphodiesterase cAMP was not found in the light fraction, while its activity in the heavy fraction was 500 pmol of cAMP/min per mg of protein. Both fractions contain bound cAMP (1-2 pmol/mg of protein) and specific sites of cAMP binding, the binding constant being approximately 10(6)M-1. The number of binding sites is 60 pmol/mg of protein for the heavy and 30 pmol/mg of protein for the light fractions. The level of phosphodiesterase activity in the heavy fraction correlates with its sensitivity to imidazole, anserine and caffeine. Imidazole and anserine increase in 1.5-1.8 times the value of Ca2+/ATP in the heavy fraction and produce no effect on Ca2+ transport by the light fraction. Caffeine decreases almost twice the Ca2+/ATP value in the heavy fraction and has practically no effect on Ca2+ absorption by enzymes of the light reticulum fraction. Imidazole and anserine activate membrane-bound phosphodiesterase, while caffeine inhibits it. It is suggested that structural rearrangements of membrane-bound phosphodiesterase under the effect of caffeine, imidazole and anserine are responsible for changes in the efficiency of Ca2+ transport by fragments of the heavy reticulum fractions."}
{"id": "PMID:184856", "title": "[Extramitochondrial energy dependent synthesis of inorganic pyrophosphate in yeasts].", "content": "In yeast Saccharomyces N.C.Y.C. 644SU3 the simplest energy donor, inorganic pyrophosphate, can be formed not only in the processes coupled with the respiratory chain, but also under conditions when mitochondrial synthesis of the compound is inhibited (glucose repression, anaerobiosis). Stimulation of inorganic pyrophosphate formed after exogeneous addition of glycolytic system components and inhibition studies suggest that under those conditions the non-mitochondrial energy-dependent formation of inorganic pyrophosphate is due to glycolytic phosphorilation.", "contents": "[Extramitochondrial energy dependent synthesis of inorganic pyrophosphate in yeasts]. In yeast Saccharomyces N.C.Y.C. 644SU3 the simplest energy donor, inorganic pyrophosphate, can be formed not only in the processes coupled with the respiratory chain, but also under conditions when mitochondrial synthesis of the compound is inhibited (glucose repression, anaerobiosis). Stimulation of inorganic pyrophosphate formed after exogeneous addition of glycolytic system components and inhibition studies suggest that under those conditions the non-mitochondrial energy-dependent formation of inorganic pyrophosphate is due to glycolytic phosphorilation."}
{"id": "PMID:184857", "title": "Endocrine and metabolic changes associated with periods of spontaneous hypoxia in fetal sheep.", "content": "Periods of spontaneously occurring hypoxia have been observed in fetal sheep. These were associated with increases in the fetal plasma concentration of glucose, lactate, free fatty acids, ACTH and corticosteroids (for a fetus close to term). These changes are similar to those observed during experimentally induced hypoxia. Hypoxia may be a mechanism by which plasma metabolites and ACTH are increased in fetal sheep under physiological conditions, particularly during labour.", "contents": "Endocrine and metabolic changes associated with periods of spontaneous hypoxia in fetal sheep. Periods of spontaneously occurring hypoxia have been observed in fetal sheep. These were associated with increases in the fetal plasma concentration of glucose, lactate, free fatty acids, ACTH and corticosteroids (for a fetus close to term). These changes are similar to those observed during experimentally induced hypoxia. Hypoxia may be a mechanism by which plasma metabolites and ACTH are increased in fetal sheep under physiological conditions, particularly during labour."}
{"id": "PMID:184858", "title": "Electron spin resonance study of the synaptosome opiate receptor: kinetics of stereospecific binding of spin labeled morphine.", "content": "Morphine, spin labeled on the 3- or 6-position has been used as the opiate ligand in a study of the time course of stereospecific opiate binding to intact synaptosomes isolated from non-cerebellar rat brain. The broadening of electron spin resonance lines induced by immobilization of the ligand on binding has been used to determine the concentration of bound opiate. The stereospecificity of the reaction was measured by comparing ligand binding in the presence of thousand-fold molar excesses of dextrorphan or levorphanol. Using both static and flow techniques, the binding process has been continuously monitored at times greater than 4.8 s after mixing spin labeled morphine with synaptosomes. It is shown that for this ligand and receptor preparation, binding takes place primarily during a delayed, abrupt process whose rate and time of onset are temperature dependent and reflect the presence of added opiate agonist or antagonist.", "contents": "Electron spin resonance study of the synaptosome opiate receptor: kinetics of stereospecific binding of spin labeled morphine. Morphine, spin labeled on the 3- or 6-position has been used as the opiate ligand in a study of the time course of stereospecific opiate binding to intact synaptosomes isolated from non-cerebellar rat brain. The broadening of electron spin resonance lines induced by immobilization of the ligand on binding has been used to determine the concentration of bound opiate. The stereospecificity of the reaction was measured by comparing ligand binding in the presence of thousand-fold molar excesses of dextrorphan or levorphanol. Using both static and flow techniques, the binding process has been continuously monitored at times greater than 4.8 s after mixing spin labeled morphine with synaptosomes. It is shown that for this ligand and receptor preparation, binding takes place primarily during a delayed, abrupt process whose rate and time of onset are temperature dependent and reflect the presence of added opiate agonist or antagonist."}
{"id": "PMID:184859", "title": "Charge-transfer interactions between metal ions and some uracil derivatives.", "content": "The interaction between Cu2+ and a few uracil derivatives has been investigated by means of electron spin resonance and optical absorption studies. It could be shown that a charge transfer interaction occurs. Its strength depends upon the electron attracting or releasing properties of the substitutents of the nucleobase.", "contents": "Charge-transfer interactions between metal ions and some uracil derivatives. The interaction between Cu2+ and a few uracil derivatives has been investigated by means of electron spin resonance and optical absorption studies. It could be shown that a charge transfer interaction occurs. Its strength depends upon the electron attracting or releasing properties of the substitutents of the nucleobase."}
{"id": "PMID:184860", "title": "Changes of cell surface configuration and regulation of cell proliferation.", "content": "The electric surface charge configuration of 3T3 and SV40-3T3 cells was characterized by determining the product of electrophoretic mobility of the cells times the viscosity of suspension medium. This quantity could be shown to change with temperature and/or treatment with calf serum or trypsin in close correlation with the effects of these agents on characteristics of cell proliferation. The present results, taken together with those of earlier studies on cell-electrophoresis and characterization of lipid constituents of the cells, support the hypothesis of a lateral phase separation in the plasmamembrane as triggering process in stimulation of proliferation of resting normal cells.", "contents": "Changes of cell surface configuration and regulation of cell proliferation. The electric surface charge configuration of 3T3 and SV40-3T3 cells was characterized by determining the product of electrophoretic mobility of the cells times the viscosity of suspension medium. This quantity could be shown to change with temperature and/or treatment with calf serum or trypsin in close correlation with the effects of these agents on characteristics of cell proliferation. The present results, taken together with those of earlier studies on cell-electrophoresis and characterization of lipid constituents of the cells, support the hypothesis of a lateral phase separation in the plasmamembrane as triggering process in stimulation of proliferation of resting normal cells."}
{"id": "PMID:184861", "title": "Constant negative pressure in the treatment of diaphragmatic paralysis secondary to birth injury.", "content": "A newborn infant with right Erb palsy and diaphragmatic paralysis was treated with CNP for respiratory failure. There was clinical and arterial blood gas improvement. Several months after treatment, respiratory symptoms had disappeared, but fluoroscopy demonstrated persistence of diaphragmatic paralysis. A review of the literature is included. CNP may allow spontaneous recovery while permitting adequate nutrition.", "contents": "Constant negative pressure in the treatment of diaphragmatic paralysis secondary to birth injury. A newborn infant with right Erb palsy and diaphragmatic paralysis was treated with CNP for respiratory failure. There was clinical and arterial blood gas improvement. Several months after treatment, respiratory symptoms had disappeared, but fluoroscopy demonstrated persistence of diaphragmatic paralysis. A review of the literature is included. CNP may allow spontaneous recovery while permitting adequate nutrition."}
{"id": "PMID:184862", "title": "Platelet interaction with human umbilical cord vascular basement membrane.", "content": "The basement membrane of the human umbilical vein was studied by electron microscopy with respect to its ultrastructure, susceptibility to digestion by collagenase or trypsin, and reactivity with human platelets. Electron microscopic examination of this vessel showed a continuous reticulated basement membrane which morphologically resembled those of mammalian capillaries and rabbit heart valves. The vascular endothelium was removed by freezing and thawing, thus uncovering the underlying connective tissue. The vessels were sliced into rings which were incubated with collagenase or trypsin. The basement lamella appeared to be susceptible to digestion by either enzyme. Platelet interaction with exposed vascular basement mambrane was studied by rotating frozen-thawed everted and noneverted rings in anticoagulated whole human blood. In heparinized or citrated blood, large aggregates of degranulated platelets adhered to collagenous controls; in contrast, the test rings with exposed basement membrane were partially covered with a monolayer of platelets which appeared to retain discoid or spherical shape and granules. In EDTA-anticoagulated blood, the collagen control rings accumulated a platelet monolayer, whereas little or no adhesion occurred on the basement membrane surface. In this system the basement membrane of the human umbilical vein appears to be a poor platelet reactive surface as compared to collagen.", "contents": "Platelet interaction with human umbilical cord vascular basement membrane. The basement membrane of the human umbilical vein was studied by electron microscopy with respect to its ultrastructure, susceptibility to digestion by collagenase or trypsin, and reactivity with human platelets. Electron microscopic examination of this vessel showed a continuous reticulated basement membrane which morphologically resembled those of mammalian capillaries and rabbit heart valves. The vascular endothelium was removed by freezing and thawing, thus uncovering the underlying connective tissue. The vessels were sliced into rings which were incubated with collagenase or trypsin. The basement lamella appeared to be susceptible to digestion by either enzyme. Platelet interaction with exposed vascular basement mambrane was studied by rotating frozen-thawed everted and noneverted rings in anticoagulated whole human blood. In heparinized or citrated blood, large aggregates of degranulated platelets adhered to collagenous controls; in contrast, the test rings with exposed basement membrane were partially covered with a monolayer of platelets which appeared to retain discoid or spherical shape and granules. In EDTA-anticoagulated blood, the collagen control rings accumulated a platelet monolayer, whereas little or no adhesion occurred on the basement membrane surface. In this system the basement membrane of the human umbilical vein appears to be a poor platelet reactive surface as compared to collagen."}
{"id": "PMID:184863", "title": "Isolation and characterization of plasma membrane from rat mesenteric arteries.", "content": "A method for isolating a plasma membrane-enriched fraction and other subcellular fractions from rat mesenteric arteries by the use of a discontinuous sucrose density gradient is decribed. Electron microscopy showed both plasma membrane and endoplasmic reticulum fractions to be composed of vesicles. 5'-Nucleotidase, alkaline phosphatase, ouabain-sensitive (Na+ + K+)-ATPase and K+-phosphatase, and phosphodiesterase I were concentrated in the plasma membrane fraction. The increase in ATP-dependent calcium uptake in the presence of oxalate was greater in the endoplasmic reticulum than in the plasma membrane fraction. The lack of inhibition of active calcium uptake by azide suggests that the plasma  membrane-enriched fraction was relatively free of mitochondrial contamination. Calcium uptake by the plasma membrane or the endoplasmic reticulum fraction was not enhanced by high-energy compounds other than ATP, and was little affected by 100 mM KCl or NaCl in the Mg++-containing medium. Subcellular fractions isolated by this method will be useful for investigating the biochemistry of small blood vessels of the rat.", "contents": "Isolation and characterization of plasma membrane from rat mesenteric arteries. A method for isolating a plasma membrane-enriched fraction and other subcellular fractions from rat mesenteric arteries by the use of a discontinuous sucrose density gradient is decribed. Electron microscopy showed both plasma membrane and endoplasmic reticulum fractions to be composed of vesicles. 5'-Nucleotidase, alkaline phosphatase, ouabain-sensitive (Na+ + K+)-ATPase and K+-phosphatase, and phosphodiesterase I were concentrated in the plasma membrane fraction. The increase in ATP-dependent calcium uptake in the presence of oxalate was greater in the endoplasmic reticulum than in the plasma membrane fraction. The lack of inhibition of active calcium uptake by azide suggests that the plasma  membrane-enriched fraction was relatively free of mitochondrial contamination. Calcium uptake by the plasma membrane or the endoplasmic reticulum fraction was not enhanced by high-energy compounds other than ATP, and was little affected by 100 mM KCl or NaCl in the Mg++-containing medium. Subcellular fractions isolated by this method will be useful for investigating the biochemistry of small blood vessels of the rat."}
{"id": "PMID:184865", "title": "Ribosome-lamellae complex in chronic lymphatic leukaemia.", "content": "The Ribosome Lamellae Complex (RLC) was found in two out of 35 patients with Chronic Lymphatic Leukaemia (CLL). The proportion of lymphocytes bearing RLC was very small (4% in the first case and less than 0.5% in the second case). The significance of this type of inclusion is discussed and the possible relationship to the circular profiles of endoplasmic reticulum is emphasized.", "contents": "Ribosome-lamellae complex in chronic lymphatic leukaemia. The Ribosome Lamellae Complex (RLC) was found in two out of 35 patients with Chronic Lymphatic Leukaemia (CLL). The proportion of lymphocytes bearing RLC was very small (4% in the first case and less than 0.5% in the second case). The significance of this type of inclusion is discussed and the possible relationship to the circular profiles of endoplasmic reticulum is emphasized."}
{"id": "PMID:184867", "title": "Effect of prostaglandin E1 on neuromuscular transmission in the rat.", "content": "1 The effect of prostaglandin E1 on neuromuscular transmission in the phrenic nerve-diaphragm muscle preparation of the rat was studied with intra- and extracellular recording techniques. 2 Prostaglandin E1, in concentrations from 10 nM, induced intermittent failures in the generation of the end-plate potential in response to repeated indirect stimulation. 3 Failures appeared abruptly, the end-plate potential behaving in an all-or-nothing fashion. The effect occurred only at 36-38 degrees C when the nerve was stimulated at 30-80 Hz and was reversible upon washing with drug-free solution. 4 Since miniature end-plate potentials were not affected, such failures must be attributed to a presynaptic action of prostaglandin E1. 5 Extracellular recording suggested that prostaglandin E1 prevented the action potential from reaching the nerve terminal.", "contents": "Effect of prostaglandin E1 on neuromuscular transmission in the rat. 1 The effect of prostaglandin E1 on neuromuscular transmission in the phrenic nerve-diaphragm muscle preparation of the rat was studied with intra- and extracellular recording techniques. 2 Prostaglandin E1, in concentrations from 10 nM, induced intermittent failures in the generation of the end-plate potential in response to repeated indirect stimulation. 3 Failures appeared abruptly, the end-plate potential behaving in an all-or-nothing fashion. The effect occurred only at 36-38 degrees C when the nerve was stimulated at 30-80 Hz and was reversible upon washing with drug-free solution. 4 Since miniature end-plate potentials were not affected, such failures must be attributed to a presynaptic action of prostaglandin E1. 5 Extracellular recording suggested that prostaglandin E1 prevented the action potential from reaching the nerve terminal."}
{"id": "PMID:184871", "title": "The effect of metiamide on acid secretion stimulated by gastrin, acetylcholine and dibutyryl cyclic adenosine 3',5'-monophosphate in the isolated whole stomach of the rat.", "content": "1 An isolated stomach preparation from immature rats is described. The lumen of the stomach was perfused and the hydrogen ion activity of the perfusate recorded continuously. 2 The preparation gave dose-dependent responses to gastrin, acetylcholine and dibutyryl cyclic adenosine 3',5'-monophosphate and these responses were readily reversed on washing out the agonist. 3 The acid secretory response to gastrin was inhibited by metiamide at concentrations of 10(-5) M and 3 X 10(-5)M. 4 The acid secretory responses to acetylcholine and dibutyryl cyclic adenosine 3',5'-monophosphate were not inhibited by concentrations of metiamide up to 10(-3) M. 5 These findings are discussed in relation to the role of histamine in the control of gastric acid secretion.", "contents": "The effect of metiamide on acid secretion stimulated by gastrin, acetylcholine and dibutyryl cyclic adenosine 3',5'-monophosphate in the isolated whole stomach of the rat. 1 An isolated stomach preparation from immature rats is described. The lumen of the stomach was perfused and the hydrogen ion activity of the perfusate recorded continuously. 2 The preparation gave dose-dependent responses to gastrin, acetylcholine and dibutyryl cyclic adenosine 3',5'-monophosphate and these responses were readily reversed on washing out the agonist. 3 The acid secretory response to gastrin was inhibited by metiamide at concentrations of 10(-5) M and 3 X 10(-5)M. 4 The acid secretory responses to acetylcholine and dibutyryl cyclic adenosine 3',5'-monophosphate were not inhibited by concentrations of metiamide up to 10(-3) M. 5 These findings are discussed in relation to the role of histamine in the control of gastric acid secretion."}
{"id": "PMID:184872", "title": "Receptors for 5-hydroxytryptamine and noradrenaline in rabbit isolated ear artery and aorta.", "content": "5-Hydroxytryptamine (5-HT) is thought to be implicated in the vascular disturbances of the external carotid artery bed associated with migraine. As part of a study of the pharmacology of some 5-HT antagonists used in the treatment of migraine we have examined the interactions of these drugs with 5-HT and noradrenaline in rabbit isolated ear artery and aortic strip. The results provide new information on the distribution of 5-HT-receptors in these preparations. In the aorta, 5-HT and noradrenaline were of similar potency in producing contractions. Methysergide produced very small contractions and was about 1000 times less potent than the other two agonists. In the ear artery noradrenaline produced monophasic vasoconstrictor responses, whereas 5-HT and methysergide produced prolonged biphasic responses. 5-HT was about 700 times less potent and methysergide about 4500 times less potent than noradrenaline. Methysergide was a better agonist in the ear artery than in the aorta. Biphasic responses to 5-HT and methysergide were also obtained in ear arteries from reserpine-treated rabbits indicating that neither agonist was acting by releasing endogenous noradrenaline. Pizotifen, cyproheptadine and phentolamine had no agonistic actions in either the aorta or ear artery. In the aorta methysergide, pizotifen and cyproheptadine were potent antagonists of 5-HT and much weaker antagonists of noradrenaline. Phentolamine possessed the opposite profile of selectivity. These results show that there are distinct receptors for 5-HT and noradrenaline in rabbit aorta. In the ear artery the pA2 values for each of the four antagonists were virtually identical against 5-HT and noradrenaline and similar to those obtained on alpha-adrenoceptors in the aorta. We conclude that 5-HT and noradrenaline act directly at alpha-receptors to produce vasoconstriction in the ear artery and that this preparation does not contain specific 5-HT receptors. This insight into the distribution of 5-HT receptors and alpha-receptors allows interpretation of the various actions of methysergide. In the aorta, methysergide was a potent antagonist at 5-HT-receptors and a weak partial agonist at alpha-receptors. In the ear artery, methysergide was a partial agonist at alpha-receptors; it was only a weak antagonist of 5-HT because this preparation does not contain specific 5-HT-receptors. The cross-reactivity demonstrated throughout these experiments indicates that 5-HT-receptors and alpha-receptors, although distinct entities, have features in common. These results are discussed in relation to the mode of action of methysergide, pizotifen and cyproheptadine in the treatment of migraine.", "contents": "Receptors for 5-hydroxytryptamine and noradrenaline in rabbit isolated ear artery and aorta. 5-Hydroxytryptamine (5-HT) is thought to be implicated in the vascular disturbances of the external carotid artery bed associated with migraine. As part of a study of the pharmacology of some 5-HT antagonists used in the treatment of migraine we have examined the interactions of these drugs with 5-HT and noradrenaline in rabbit isolated ear artery and aortic strip. The results provide new information on the distribution of 5-HT-receptors in these preparations. In the aorta, 5-HT and noradrenaline were of similar potency in producing contractions. Methysergide produced very small contractions and was about 1000 times less potent than the other two agonists. In the ear artery noradrenaline produced monophasic vasoconstrictor responses, whereas 5-HT and methysergide produced prolonged biphasic responses. 5-HT was about 700 times less potent and methysergide about 4500 times less potent than noradrenaline. Methysergide was a better agonist in the ear artery than in the aorta. Biphasic responses to 5-HT and methysergide were also obtained in ear arteries from reserpine-treated rabbits indicating that neither agonist was acting by releasing endogenous noradrenaline. Pizotifen, cyproheptadine and phentolamine had no agonistic actions in either the aorta or ear artery. In the aorta methysergide, pizotifen and cyproheptadine were potent antagonists of 5-HT and much weaker antagonists of noradrenaline. Phentolamine possessed the opposite profile of selectivity. These results show that there are distinct receptors for 5-HT and noradrenaline in rabbit aorta. In the ear artery the pA2 values for each of the four antagonists were virtually identical against 5-HT and noradrenaline and similar to those obtained on alpha-adrenoceptors in the aorta. We conclude that 5-HT and noradrenaline act directly at alpha-receptors to produce vasoconstriction in the ear artery and that this preparation does not contain specific 5-HT receptors. This insight into the distribution of 5-HT receptors and alpha-receptors allows interpretation of the various actions of methysergide. In the aorta, methysergide was a potent antagonist at 5-HT-receptors and a weak partial agonist at alpha-receptors. In the ear artery, methysergide was a partial agonist at alpha-receptors; it was only a weak antagonist of 5-HT because this preparation does not contain specific 5-HT-receptors. The cross-reactivity demonstrated throughout these experiments indicates that 5-HT-receptors and alpha-receptors, although distinct entities, have features in common. These results are discussed in relation to the mode of action of methysergide, pizotifen and cyproheptadine in the treatment of migraine."}
{"id": "PMID:184875", "title": "Asthma deaths in Cardiff 1963-74: 53 deaths in hospital.", "content": "In a study of factors associated with death from bronchial asthma in hospital 53 patients were investigated. Typically the fatal attack persisted for several days before admission to hospital and normally occurred in patients with a long history of asthma. The patient or doctor often underestimated the severity of the attack. On admission most patients were severely ill, and over a third died within 24 hours. Peak flow rate and blood gases were rarely measured. Corticosteroid treatment was often underused, and patients rarely received assisted ventilation before death. Infection played a part in 14 deaths, five of them associated with assisted ventilation. Admitting asthmatics to a special respiratory ward with facilities for standardised assessment and treatment and introducing a self-admission service may help to prevent some of these deaths.", "contents": "Asthma deaths in Cardiff 1963-74: 53 deaths in hospital. In a study of factors associated with death from bronchial asthma in hospital 53 patients were investigated. Typically the fatal attack persisted for several days before admission to hospital and normally occurred in patients with a long history of asthma. The patient or doctor often underestimated the severity of the attack. On admission most patients were severely ill, and over a third died within 24 hours. Peak flow rate and blood gases were rarely measured. Corticosteroid treatment was often underused, and patients rarely received assisted ventilation before death. Infection played a part in 14 deaths, five of them associated with assisted ventilation. Admitting asthmatics to a special respiratory ward with facilities for standardised assessment and treatment and introducing a self-admission service may help to prevent some of these deaths."}
{"id": "PMID:184877", "title": "Studies on the pharmacology of neurones in the nucleus accumbens of the rat.", "content": "A study was made of the effects of iontophoretically applied drugs on single neurones in the nucleus accumgens and caudate nucleus of rats anaesthetized with urethane. Neurones in the caudate nucleus were inhibited by dopamine, dibutyryl cyclic AMP, ADTN and ergometrine. Acetylcholine and homocysteic acid caused excitation of striatal neurones. In the nucleus accumbens neurones were inhibited by dopamine, ADTN, ergometrine, dibutyryl cyclic AMP, glycine and gamma-aminobutyric acid. The responses of glycine and gamma-aminobutyric acid were antagonised by strychnine and picrotoxin, respectively. Acetylcholine and homocysteic acid caused excitation of neurones in the nucleus acumbens; the effects of acetylcholine were blocked by atropine. The results are consistent with the suggestion that dopamine is an inhibitory transmitter in the nucleus accumbens and in the caudate nucleus and support the  hypothesis that the effects of dopamine are mediated by cyclic AMP. The locomotor stimulants ADTN and ergometrine mimicked the inhibitory actions of dopamine in both the striatum and in the nucleus accumbens. These results support the suggestion that dopamine receptors in the nucleus accumbens are involved in the actions of locomotor stimulant drugs.", "contents": "Studies on the pharmacology of neurones in the nucleus accumbens of the rat. A study was made of the effects of iontophoretically applied drugs on single neurones in the nucleus accumgens and caudate nucleus of rats anaesthetized with urethane. Neurones in the caudate nucleus were inhibited by dopamine, dibutyryl cyclic AMP, ADTN and ergometrine. Acetylcholine and homocysteic acid caused excitation of striatal neurones. In the nucleus accumbens neurones were inhibited by dopamine, ADTN, ergometrine, dibutyryl cyclic AMP, glycine and gamma-aminobutyric acid. The responses of glycine and gamma-aminobutyric acid were antagonised by strychnine and picrotoxin, respectively. Acetylcholine and homocysteic acid caused excitation of neurones in the nucleus acumbens; the effects of acetylcholine were blocked by atropine. The results are consistent with the suggestion that dopamine is an inhibitory transmitter in the nucleus accumbens and in the caudate nucleus and support the  hypothesis that the effects of dopamine are mediated by cyclic AMP. The locomotor stimulants ADTN and ergometrine mimicked the inhibitory actions of dopamine in both the striatum and in the nucleus accumbens. These results support the suggestion that dopamine receptors in the nucleus accumbens are involved in the actions of locomotor stimulant drugs."}
{"id": "PMID:184878", "title": "Interactions of nigrostriate synaptic transmission, iontophoretic O-methylated phenethylamines, dopamine, apomorphine and acetylcholine.", "content": "Recordings were made from, and drugs applied to, neurons in the caudate nucleus of unanesthetized cats, using multibarrel micropipette electrodes. The substantia nigra was stimulated by sterotactically placed electrodes. Three O-methylated derivatives of dopamine, meta-methoxyphenethylamine (m-MPEA), para-methosy-phenethylamine (p-MPEA) and 3,4-demethoxyphenethylamine (DIMPEA), inhibited most, excited a few, and had no detectable effect on a substantial number of the cells upon which they were tested. A statistically significant correlation was found between the effects of dopamine (DA) and the three O-methylated derivatives on the same populations of cells. Iontophoretic release of the O-methylated derivatives could not prevent the actions of DA, nor could it block synaptically mediated effects of the nigrostriate pathway. It is concluded that the three O-methylated products are partial agonists of DA. The findings are difficult to reconcile with the suggestion that the experimental parkinsonian-like symptoms caused by O-methylated phenethylamines are the consequence of blockade of dopaminergic synapses. No correlation, negative or positive, was found between the effects of DA and of acetylcholine (ACh). The findings do not support the theory that balanced sets of antagonistic synapses, one dopaminergic, the other cholinervic, operate upon individual neurons in the caudate nucleus. Apomorphine and dopamine were shown to have similar effects on a substantial number of neurons, even though the onset and offset of the effect of apomorphine were slower than those of DA. This observation agrees with the suggestion that some of the central effects of apomorphine are due to an action at dopaminoceptive receptor sites.", "contents": "Interactions of nigrostriate synaptic transmission, iontophoretic O-methylated phenethylamines, dopamine, apomorphine and acetylcholine. Recordings were made from, and drugs applied to, neurons in the caudate nucleus of unanesthetized cats, using multibarrel micropipette electrodes. The substantia nigra was stimulated by sterotactically placed electrodes. Three O-methylated derivatives of dopamine, meta-methoxyphenethylamine (m-MPEA), para-methosy-phenethylamine (p-MPEA) and 3,4-demethoxyphenethylamine (DIMPEA), inhibited most, excited a few, and had no detectable effect on a substantial number of the cells upon which they were tested. A statistically significant correlation was found between the effects of dopamine (DA) and the three O-methylated derivatives on the same populations of cells. Iontophoretic release of the O-methylated derivatives could not prevent the actions of DA, nor could it block synaptically mediated effects of the nigrostriate pathway. It is concluded that the three O-methylated products are partial agonists of DA. The findings are difficult to reconcile with the suggestion that the experimental parkinsonian-like symptoms caused by O-methylated phenethylamines are the consequence of blockade of dopaminergic synapses. No correlation, negative or positive, was found between the effects of DA and of acetylcholine (ACh). The findings do not support the theory that balanced sets of antagonistic synapses, one dopaminergic, the other cholinervic, operate upon individual neurons in the caudate nucleus. Apomorphine and dopamine were shown to have similar effects on a substantial number of neurons, even though the onset and offset of the effect of apomorphine were slower than those of DA. This observation agrees with the suggestion that some of the central effects of apomorphine are due to an action at dopaminoceptive receptor sites."}
{"id": "PMID:184879", "title": "Nervous system antigen-5, an antigenic cell surface component of neuroectodermal origin.", "content": "The antigenic cell surface component NS-5 (nervous system antigen-5) is recognized by antiserum raised in C3H.SW/Sn mice against cerebellum of 4-day-old C57BL/6J mice. When analyzed in the cytotoxicity test the antiserum detects a cell surface antigen or set of antigens present not only an cerebellum but also other parts of the central nervous system, including retina, as well as on mature spermatozoa and to a lesser degree on kidney. All other non-neural tissues tested, liver, splee, thymocytes, muscle, testis, adrenal gland and epidermis do not express detectable amounts of the antigen. Among seven murine tumors of the nervous system, medulloepithelioma shows high levels of NS-5 expression, whereas neuroblastoma Cl300, glioma G26, glioblastome, ependymoblastoma, ependymoblastoma EPA and glioblastoma G26l do not carry detectable NS-5. All mouse strains tested (C57BL/6J, C3H.SW/Sn, C3H/HeDiSn, A/J, AKR/J, BALB/cJ and DBA/2) express similar levels of NS-5. The antigen is demonstrable not only on postnatal day 4 neural tissue, but also in lower amounts on adult nervous system. On embryonic day 9, the earliest stage tested, and at all subsequent stages during embryonic development, NS-K is already present in brain and spinal cord, but not in gut.", "contents": "Nervous system antigen-5, an antigenic cell surface component of neuroectodermal origin. The antigenic cell surface component NS-5 (nervous system antigen-5) is recognized by antiserum raised in C3H.SW/Sn mice against cerebellum of 4-day-old C57BL/6J mice. When analyzed in the cytotoxicity test the antiserum detects a cell surface antigen or set of antigens present not only an cerebellum but also other parts of the central nervous system, including retina, as well as on mature spermatozoa and to a lesser degree on kidney. All other non-neural tissues tested, liver, splee, thymocytes, muscle, testis, adrenal gland and epidermis do not express detectable amounts of the antigen. Among seven murine tumors of the nervous system, medulloepithelioma shows high levels of NS-5 expression, whereas neuroblastoma Cl300, glioma G26, glioblastome, ependymoblastoma, ependymoblastoma EPA and glioblastoma G26l do not carry detectable NS-5. All mouse strains tested (C57BL/6J, C3H.SW/Sn, C3H/HeDiSn, A/J, AKR/J, BALB/cJ and DBA/2) express similar levels of NS-5. The antigen is demonstrable not only on postnatal day 4 neural tissue, but also in lower amounts on adult nervous system. On embryonic day 9, the earliest stage tested, and at all subsequent stages during embryonic development, NS-K is already present in brain and spinal cord, but not in gut."}
{"id": "PMID:184880", "title": "Autonomic nerves, mast cells, and amine receptors in human brain vessels. A histochemical and pharmacological study.", "content": "The studies were performed on operation material from 17- to 63-year-old patients and on fetuses at 19-23 weeks gestational age. Formaldehyde histofluorescence showed the presence of numerous perivascular adrenergic nerves around pial and intracerebral vessels, the carotid system being better supplied than the vertebral system. Cholinergic nerves, visualized by the cholinesterase technique, followed the adrenergic fibers in the plexus formations of the pial arterial system. Histamine-containing mast cells, often with a perivascular distribution, were located with the o-phthaldiadehyde method. Transmural electrical stimulation of the perivascular nerves contracted isolated pieces of pial arteries in a frequency-dependent manner, and the response was inhibited by the adrenergic nerve blocking agent, guanethidine. On the basis of the relative potency of various amines and related compounds in producing a motor response of isolated pial arteries, and the mode of inhibition caused by specific antagonists, various amine receptors could be demonstrated: adrenergic alpha-receptors (mediating contraction) and beta-receptors (dilation), cholinergic muscarinic receptors (dilation) and histamine H2-receptors (mediating dilation). Thus, the amine mechanisms demonstrated in human brain vessels appear to be principally the same of those shown in more extensive studies on laboratory animals.", "contents": "Autonomic nerves, mast cells, and amine receptors in human brain vessels. A histochemical and pharmacological study. The studies were performed on operation material from 17- to 63-year-old patients and on fetuses at 19-23 weeks gestational age. Formaldehyde histofluorescence showed the presence of numerous perivascular adrenergic nerves around pial and intracerebral vessels, the carotid system being better supplied than the vertebral system. Cholinergic nerves, visualized by the cholinesterase technique, followed the adrenergic fibers in the plexus formations of the pial arterial system. Histamine-containing mast cells, often with a perivascular distribution, were located with the o-phthaldiadehyde method. Transmural electrical stimulation of the perivascular nerves contracted isolated pieces of pial arteries in a frequency-dependent manner, and the response was inhibited by the adrenergic nerve blocking agent, guanethidine. On the basis of the relative potency of various amines and related compounds in producing a motor response of isolated pial arteries, and the mode of inhibition caused by specific antagonists, various amine receptors could be demonstrated: adrenergic alpha-receptors (mediating contraction) and beta-receptors (dilation), cholinergic muscarinic receptors (dilation) and histamine H2-receptors (mediating dilation). Thus, the amine mechanisms demonstrated in human brain vessels appear to be principally the same of those shown in more extensive studies on laboratory animals."}
{"id": "PMID:184881", "title": "Modulation in the sensitivity of noradrenergic receptors in the CNS studied by the responsiveness of the cyclic AMP system.", "content": "Various characteristics of the altered responsiveness to noradrenaline (NA) of the cyclic Amp (cAMP) generating system of cortical brain slices have been studied in rat after chronic reserpine treatment and in mice after chronic D-amphetamine treatment. Supersensitivity of the cAMP system to NA following reserpine treatment and subsensitivity after D-amphetamine treatment exhibit many common features. Firstly, in both cases the modified responsiveness to NA occurs rapidly after the beginning of the treatment (one day for reserpine and 5 h after amphetamine) and recovers slowly after the end of the treatment. Additionally, the altered states of sensitivity of the cAMP system to NA are the result of a modification of the maximal response rather than of an altered affinity of the system to NA. Since, following D-amphetamine treatment the change of sensitivity is still apparent in the presence of a potent phosphodiesterase inhibitor, the involvement of a gross alteration of phosphodiesterase activity is unlikely. In this case too, while the response to adenosine is slightly decreased, the responses to dopamine and serotonin of the cAMP system observed in brain slices following D-amphetamine treatment is not detected in a cell-free preparation. Thus, it appears that drug treatments, modifying synaptic transmission in opposite directions, lead also to changes in opposite directions of the responsiveness of the cAMP system to NA. The hypothesis that the mechanisms underlying such phenomena are related to a modified number of functional noradrenergic receptors is discussed.", "contents": "Modulation in the sensitivity of noradrenergic receptors in the CNS studied by the responsiveness of the cyclic AMP system. Various characteristics of the altered responsiveness to noradrenaline (NA) of the cyclic Amp (cAMP) generating system of cortical brain slices have been studied in rat after chronic reserpine treatment and in mice after chronic D-amphetamine treatment. Supersensitivity of the cAMP system to NA following reserpine treatment and subsensitivity after D-amphetamine treatment exhibit many common features. Firstly, in both cases the modified responsiveness to NA occurs rapidly after the beginning of the treatment (one day for reserpine and 5 h after amphetamine) and recovers slowly after the end of the treatment. Additionally, the altered states of sensitivity of the cAMP system to NA are the result of a modification of the maximal response rather than of an altered affinity of the system to NA. Since, following D-amphetamine treatment the change of sensitivity is still apparent in the presence of a potent phosphodiesterase inhibitor, the involvement of a gross alteration of phosphodiesterase activity is unlikely. In this case too, while the response to adenosine is slightly decreased, the responses to dopamine and serotonin of the cAMP system observed in brain slices following D-amphetamine treatment is not detected in a cell-free preparation. Thus, it appears that drug treatments, modifying synaptic transmission in opposite directions, lead also to changes in opposite directions of the responsiveness of the cAMP system to NA. The hypothesis that the mechanisms underlying such phenomena are related to a modified number of functional noradrenergic receptors is discussed."}
{"id": "PMID:184883", "title": "Ultrastructural comparisons of neurons of supraoptic and circularis nuclei in normal and dehydrated rats.", "content": "A quantitative ultrastructural investigation was undertaken to compare the nucleus circularis (NC) and supraoptic nucleus (SON) of the rat both under normal and water-deprived conditions. NC was found to have dramatically more of its cells and membrane surface involved in direct soma-somatic contact than the SON. Water deprivation, even for one day, brought about a significant increase in both percentage of cells and membrane surface in contact in both nuclei, apparently by the retraction of fine glial processes from between the somata. The normal NC was made up of only one ultrastructurally identifiable cell type. The normal NC had no cells showing expanded endoplasmic reticulum, although these were seen following 5 days (but not 1 day) of water deprivation. The normal SON did have 4.4% of its cells showing expanded endoplasmic reticulum. This percentage significantly increased following water deprivation. The vesicle population per area of cytoplasm was very similar between the two normal nuclei. One day of water deprivation brought about a significant increase in less than 800 A vesicles in NC but not the SON. Five days of water deprivation resulted in a significant decrease in the lysosomal population per unit area in both nuclei. Vesicle changes have been discussed in relation to the volume changes in the cells.", "contents": "Ultrastructural comparisons of neurons of supraoptic and circularis nuclei in normal and dehydrated rats. A quantitative ultrastructural investigation was undertaken to compare the nucleus circularis (NC) and supraoptic nucleus (SON) of the rat both under normal and water-deprived conditions. NC was found to have dramatically more of its cells and membrane surface involved in direct soma-somatic contact than the SON. Water deprivation, even for one day, brought about a significant increase in both percentage of cells and membrane surface in contact in both nuclei, apparently by the retraction of fine glial processes from between the somata. The normal NC was made up of only one ultrastructurally identifiable cell type. The normal NC had no cells showing expanded endoplasmic reticulum, although these were seen following 5 days (but not 1 day) of water deprivation. The normal SON did have 4.4% of its cells showing expanded endoplasmic reticulum. This percentage significantly increased following water deprivation. The vesicle population per area of cytoplasm was very similar between the two normal nuclei. One day of water deprivation brought about a significant increase in less than 800 A vesicles in NC but not the SON. Five days of water deprivation resulted in a significant decrease in the lysosomal population per unit area in both nuclei. Vesicle changes have been discussed in relation to the volume changes in the cells."}
{"id": "PMID:184884", "title": "Feeding and body temperature in the rat: diencephalic localization of changes produced by excess calcium ions.", "content": "In the unanesthetized rat, Ca++ ions in solutions ranging from 2.6 to 112.0 mM in excess of the normal level in CSF were applied at different sites in the brain and by three separate procedures, Colonic temperature was monitored and in certain experiments, the amount of food pellets and water consumed was measured simultaneously following the administration of excess Ca++ ions. An infusion into the lateral cerebral ventricle of excess calcium in a volume of 5.0 mul produced a concentration-dependent hypothermia, This fall in temperature was not attenuated by a prior intraventricular infusion of mecamylamine and often enhanced by atropine. Depending on the site, a microinjection of excess Ca++ ions in a volume of 0.5 to 1.0 mul directly into the hypothalamus produced hypothermia or feeding. The sites of maximum sensitivity at which excess calcium caused a decline in temperature were clustered in the caudal hypothalamus, whereas those at which calcium elicited feeding were distributed widely in caudo-lateral, medial and rostral hypothalamic areas. Push-pull perfusions at a rate of 20 to 25 mul per min for 10 to 20 min at homologous sites caused similar responses but the cation concentration required to evoke feeding or hypothermia was significantly less than that of either microinjection or intraventricular infusion. These findings demonstrate species continuity in the rat concerning anatomical localization of the postulated set-point mechanism for body temperature. Several different pathways in the feeding system are affected by an alteration in the hypothalamic level of calcium.", "contents": "Feeding and body temperature in the rat: diencephalic localization of changes produced by excess calcium ions. In the unanesthetized rat, Ca++ ions in solutions ranging from 2.6 to 112.0 mM in excess of the normal level in CSF were applied at different sites in the brain and by three separate procedures, Colonic temperature was monitored and in certain experiments, the amount of food pellets and water consumed was measured simultaneously following the administration of excess Ca++ ions. An infusion into the lateral cerebral ventricle of excess calcium in a volume of 5.0 mul produced a concentration-dependent hypothermia, This fall in temperature was not attenuated by a prior intraventricular infusion of mecamylamine and often enhanced by atropine. Depending on the site, a microinjection of excess Ca++ ions in a volume of 0.5 to 1.0 mul directly into the hypothalamus produced hypothermia or feeding. The sites of maximum sensitivity at which excess calcium caused a decline in temperature were clustered in the caudal hypothalamus, whereas those at which calcium elicited feeding were distributed widely in caudo-lateral, medial and rostral hypothalamic areas. Push-pull perfusions at a rate of 20 to 25 mul per min for 10 to 20 min at homologous sites caused similar responses but the cation concentration required to evoke feeding or hypothermia was significantly less than that of either microinjection or intraventricular infusion. These findings demonstrate species continuity in the rat concerning anatomical localization of the postulated set-point mechanism for body temperature. Several different pathways in the feeding system are affected by an alteration in the hypothalamic level of calcium."}
{"id": "PMID:184885", "title": "Sleep cycles in cats during chronic electrical stimulation of the area postrema and the anterior raphe.", "content": "Sleep-waking profiles were obtained from 130 7 hr stimulation-EEG recording sessions in a series of cats bearing chronically implanted stimulating electrodes in the regions of the area postrema and anterior raphe nuclei. The results indicated that: (a) during electrical stimulation of the region of the area postrema with 0.5 or 10 Hz at 1 and 2 mA there were significant increases in the occurrence of the deeper aspects of slow-wave sleep and in REM sleep. These elevations were significant in comparison to nonstimulation baselines and to sleep profiles obtained during stimulation of points located dorsal and anterior to the area postrema. (b) Stimulation of the medial reticular formation including the anterior raphe using the same parameters employed for the area postrema did not alter the occurrence of any stage of sleep. These findings indicate that the region of the area postrema may be more involved in the generation of sleep than the anterior raphe nuclei.", "contents": "Sleep cycles in cats during chronic electrical stimulation of the area postrema and the anterior raphe. Sleep-waking profiles were obtained from 130 7 hr stimulation-EEG recording sessions in a series of cats bearing chronically implanted stimulating electrodes in the regions of the area postrema and anterior raphe nuclei. The results indicated that: (a) during electrical stimulation of the region of the area postrema with 0.5 or 10 Hz at 1 and 2 mA there were significant increases in the occurrence of the deeper aspects of slow-wave sleep and in REM sleep. These elevations were significant in comparison to nonstimulation baselines and to sleep profiles obtained during stimulation of points located dorsal and anterior to the area postrema. (b) Stimulation of the medial reticular formation including the anterior raphe using the same parameters employed for the area postrema did not alter the occurrence of any stage of sleep. These findings indicate that the region of the area postrema may be more involved in the generation of sleep than the anterior raphe nuclei."}
{"id": "PMID:184890", "title": "[Action of the collagenase on the morphogenesis of the duck embryonic urophygial gland cultured in vitro].", "content": "Collagenase prevents in vitro the uropygial invaginations differentiation and the ectodermal glandular buds development. The basal lamina and the extracellular material disappear. These data suggest that collagen is essential to preen gland morphogenesis.", "contents": "[Action of the collagenase on the morphogenesis of the duck embryonic urophygial gland cultured in vitro]. Collagenase prevents in vitro the uropygial invaginations differentiation and the ectodermal glandular buds development. The basal lamina and the extracellular material disappear. These data suggest that collagen is essential to preen gland morphogenesis."}
{"id": "PMID:184886", "title": "Power spectral analysis of EEG activity obtained from cortical and subcortical sites during the vigilance states of the cat.", "content": "There is considerable evidence that the raph\u00e9 system and the region of the nucleus tractus solitarious (NTS), including the area postrema, play significant roles in slow-wave sleep mechanisms and in EEG synchronization. Studies of the interactions between these systems and the neocortex are much needed. If neuronal activity in these lower brainstem regions regulates the degree of cortical synchrony then a high degree of correspondence between the EEG of the area postrema or raph\u00e9 complex with that of the cortex might be expected. In order to quantitate the reequency characteristics of the EEG obtained from these subcortical sites (nucleus raph\u00e9 dorsalis, area postrema, as well as anatomical controls adjacent to these regions) during the different vigilance states (waking, slow-wave sleep, REM sleep) in the cat, power spectral analyses techniques were employed. Comparison of these subcortical spectral characteristic with those obtained from cortical (frontal and occipital) sites during the same vigilance state, show that the spectral measures elicited from the region of the area postrema closely correspond to that of the cortex, particularly during slow-wave sleep. On the other hand, the EEG of the anterior portion of the raph\u00e9 region, although exhibiting a substantial low frequency component during slow-wave sleep in comparison to wakefulness does not show a statistically significant shift to low frequencies such as occurs in the area postrema or the cortex. These results suggest that the increases in the low frequency content of the cortical EEG sites during slow-wave sleep results from synchronizing inputs from the area postrema to a greater extent than from the raph\u00e9 complex.", "contents": "Power spectral analysis of EEG activity obtained from cortical and subcortical sites during the vigilance states of the cat. There is considerable evidence that the raph\u00e9 system and the region of the nucleus tractus solitarious (NTS), including the area postrema, play significant roles in slow-wave sleep mechanisms and in EEG synchronization. Studies of the interactions between these systems and the neocortex are much needed. If neuronal activity in these lower brainstem regions regulates the degree of cortical synchrony then a high degree of correspondence between the EEG of the area postrema or raph\u00e9 complex with that of the cortex might be expected. In order to quantitate the reequency characteristics of the EEG obtained from these subcortical sites (nucleus raph\u00e9 dorsalis, area postrema, as well as anatomical controls adjacent to these regions) during the different vigilance states (waking, slow-wave sleep, REM sleep) in the cat, power spectral analyses techniques were employed. Comparison of these subcortical spectral characteristic with those obtained from cortical (frontal and occipital) sites during the same vigilance state, show that the spectral measures elicited from the region of the area postrema closely correspond to that of the cortex, particularly during slow-wave sleep. On the other hand, the EEG of the anterior portion of the raph\u00e9 region, although exhibiting a substantial low frequency component during slow-wave sleep in comparison to wakefulness does not show a statistically significant shift to low frequencies such as occurs in the area postrema or the cortex. These results suggest that the increases in the low frequency content of the cortical EEG sites during slow-wave sleep results from synchronizing inputs from the area postrema to a greater extent than from the raph\u00e9 complex."}
{"id": "PMID:184891", "title": "[Ultrastructural aspects of cells with 3 beta-HSDH (delta-5-betahydroxysteroid dehydrogenase) activity in female ducks. I. Female Peking duck (Anas platyrhynchos)].", "content": "The cells making up the thick internal theca of the follicle of the Peking duck and which contain an active 3 beta HSDH enzyme have a developed smooth reticulum, tubular crested mitochondria, a considerable load in slightly osmiophilic lipid inclusions; all of these characteristics are those of steroid cells. Various physiological states of these cells juxtapose themselves in different proportions according to the season.", "contents": "[Ultrastructural aspects of cells with 3 beta-HSDH (delta-5-betahydroxysteroid dehydrogenase) activity in female ducks. I. Female Peking duck (Anas platyrhynchos)]. The cells making up the thick internal theca of the follicle of the Peking duck and which contain an active 3 beta HSDH enzyme have a developed smooth reticulum, tubular crested mitochondria, a considerable load in slightly osmiophilic lipid inclusions; all of these characteristics are those of steroid cells. Various physiological states of these cells juxtapose themselves in different proportions according to the season."}
{"id": "PMID:184887", "title": "Low level potentiation of the brain stem laryngeal reflex.", "content": "Trains of electrical stimuli were applied to the superior laryngeal nerve (SLN) innervating the upper respiratory tract while evoked potentials were recorded from the recurrent nerve (RN) which innervates the intrinsic laryngeal muscles. Responses of this brain stem reflex (central delay 3.5-5.0 msec) were compared to the post-tetanic potentiation (PTP) of the polysynaptic ventral root response (L6-S1) with trains of stimuli applied to the dorsal root of adult cats. Stimulation of the SLN with a train of pulses varying from 10-45/sec evokes an initial depression of the polysynaptic potential from the RN followed by a low but sustained increase in the amplitude of the integrated signal (1.2-1.6x) lasting 45-130 msec and lacking the early maximum amplitude as seen in the PTP of the polysynaptic spinal reflex. Both the early and late components of the superior laryngeal-recurrent nerve reflex (SLN-RN) demonstrate potentiation whereas the shortest latency components of the spinal reflex account for most of the PTP. Systemic administration of strychnine sulfate (dosage: 0.03-0.45 mg/kg) does not alter the normalized PTP of the SLN-RN reflex despite enhancement of both early and late components of the reflex following control stimuli at 1/sec.", "contents": "Low level potentiation of the brain stem laryngeal reflex. Trains of electrical stimuli were applied to the superior laryngeal nerve (SLN) innervating the upper respiratory tract while evoked potentials were recorded from the recurrent nerve (RN) which innervates the intrinsic laryngeal muscles. Responses of this brain stem reflex (central delay 3.5-5.0 msec) were compared to the post-tetanic potentiation (PTP) of the polysynaptic ventral root response (L6-S1) with trains of stimuli applied to the dorsal root of adult cats. Stimulation of the SLN with a train of pulses varying from 10-45/sec evokes an initial depression of the polysynaptic potential from the RN followed by a low but sustained increase in the amplitude of the integrated signal (1.2-1.6x) lasting 45-130 msec and lacking the early maximum amplitude as seen in the PTP of the polysynaptic spinal reflex. Both the early and late components of the superior laryngeal-recurrent nerve reflex (SLN-RN) demonstrate potentiation whereas the shortest latency components of the spinal reflex account for most of the PTP. Systemic administration of strychnine sulfate (dosage: 0.03-0.45 mg/kg) does not alter the normalized PTP of the SLN-RN reflex despite enhancement of both early and late components of the reflex following control stimuli at 1/sec."}
{"id": "PMID:184892", "title": "[Ultrastructural aspects of cells with 3 beta-HSDH (delta 5-3 betahydroxysteroid dehydrogenase) activity in female ducks. II. Female Barbary ducks (Cairina moschata)].", "content": "The cells making up the thin internal theca of the follicle of the Barbary duck and which contain are 3 beta HSDH enzyme show all of the ultrastructural characteristics of steroid cells: a well-developed smooth reticulum, tubular cristae mitochondria, a considerable load in lipid inclusionologous cells of the Peking duck since they are constantly more dense and their cristae are bigger and less numerous.", "contents": "[Ultrastructural aspects of cells with 3 beta-HSDH (delta 5-3 betahydroxysteroid dehydrogenase) activity in female ducks. II. Female Barbary ducks (Cairina moschata)]. The cells making up the thin internal theca of the follicle of the Barbary duck and which contain are 3 beta HSDH enzyme show all of the ultrastructural characteristics of steroid cells: a well-developed smooth reticulum, tubular cristae mitochondria, a considerable load in lipid inclusionologous cells of the Peking duck since they are constantly more dense and their cristae are bigger and less numerous."}
{"id": "PMID:184893", "title": "[Cytochemical aspects of human polynuclear neutrophils under the in vitro and in vivo action of TRH].", "content": "A TRH fixation in vitro occurs at the level of the human polynuclear neutrophil, which suggests putative membrane receptor (s) for the hypothalamic hormone. After TRH administration, enzyme modifications (myeloperoxydase, alkaline phosphatase) and metabolism changes (PAS, Sudan black) happen in vivo within the neutrophil, showing a functional activation of that blood cell. Two processes may be considered to explain those data: 1) the TRH is directly fixed, as observed in vitro; 2) a mediate hormone (TSH, T4, T3) is released capable of binding the granulocyte membrane.", "contents": "[Cytochemical aspects of human polynuclear neutrophils under the in vitro and in vivo action of TRH]. A TRH fixation in vitro occurs at the level of the human polynuclear neutrophil, which suggests putative membrane receptor (s) for the hypothalamic hormone. After TRH administration, enzyme modifications (myeloperoxydase, alkaline phosphatase) and metabolism changes (PAS, Sudan black) happen in vivo within the neutrophil, showing a functional activation of that blood cell. Two processes may be considered to explain those data: 1) the TRH is directly fixed, as observed in vitro; 2) a mediate hormone (TSH, T4, T3) is released capable of binding the granulocyte membrane."}
{"id": "PMID:184894", "title": "The effect of calcium oncardiac phosphorylase activation, contractile force and cyclic AMP in euthyroid and hyperthyroid rat hearts.", "content": "Calcium chloride injected into isolated perfused rat hearts produced a positive inotropic effect and increased the levels of phosphorylase a (EC 2.4.1.1). The increase in enzyme activity lagged behind the inotropic effect. Pretreatment of animals with thyroid hormone enhanced the ability of noradrenaline to activate phosphorylase but did not affect the inotropic or phosphorylase activating effect of calcium. Thyroid hormone pretreatment did enhance the chronotropic effect of calcium. Calcium did not affect the cardiac levels of cyclic AMP. It is concluded that calcium can activate phosphorylase by a mechanism other than cyclic AMP and that the enhancement of adrenergic amine-induced phosphorylase activation by thyroid hormone is not a calcium mediated event.", "contents": "The effect of calcium oncardiac phosphorylase activation, contractile force and cyclic AMP in euthyroid and hyperthyroid rat hearts. Calcium chloride injected into isolated perfused rat hearts produced a positive inotropic effect and increased the levels of phosphorylase a (EC 2.4.1.1). The increase in enzyme activity lagged behind the inotropic effect. Pretreatment of animals with thyroid hormone enhanced the ability of noradrenaline to activate phosphorylase but did not affect the inotropic or phosphorylase activating effect of calcium. Thyroid hormone pretreatment did enhance the chronotropic effect of calcium. Calcium did not affect the cardiac levels of cyclic AMP. It is concluded that calcium can activate phosphorylase by a mechanism other than cyclic AMP and that the enhancement of adrenergic amine-induced phosphorylase activation by thyroid hormone is not a calcium mediated event."}
{"id": "PMID:184895", "title": "The release and characterization of some periplasm-located enzymes of Pseudomona aeruginosa.", "content": "Pseudomonas aeruginosa (ATCC 9027) releases four periplasm-located enzymes, i.e., ribonuclease (EC 3.1.4.22; EC 3.1.4.23), alkaline phosphatase (EC 3.1.3.1), cyclic-2', 3'-phosphodiesterase (EC 3.1.4.d), and 5'-nucleotidase (EC 3.1.3.5) into the medium during growth. Ribonuclease and alkaline phosphatase are classed as enzymes which are readily extracted by osmotic shock and spheroplast formation whereas cyclic-2',3'-phosphodiesterase and 5'-nucleotidase are classed as enzymes which are not readily extracted by these procedures. In view of the relative ease of extraction of the former enzymes it is suggested that the lattter enzymes, cyclic-2',3'-phosphodiesterase and 5'-nucleotidase, are bound and located in the periplasm in a manner different to ribonuclease and alkaline phosphatase.", "contents": "The release and characterization of some periplasm-located enzymes of Pseudomona aeruginosa. Pseudomonas aeruginosa (ATCC 9027) releases four periplasm-located enzymes, i.e., ribonuclease (EC 3.1.4.22; EC 3.1.4.23), alkaline phosphatase (EC 3.1.3.1), cyclic-2', 3'-phosphodiesterase (EC 3.1.4.d), and 5'-nucleotidase (EC 3.1.3.5) into the medium during growth. Ribonuclease and alkaline phosphatase are classed as enzymes which are readily extracted by osmotic shock and spheroplast formation whereas cyclic-2',3'-phosphodiesterase and 5'-nucleotidase are classed as enzymes which are not readily extracted by these procedures. In view of the relative ease of extraction of the former enzymes it is suggested that the lattter enzymes, cyclic-2',3'-phosphodiesterase and 5'-nucleotidase, are bound and located in the periplasm in a manner different to ribonuclease and alkaline phosphatase."}
{"id": "PMID:184896", "title": "Comparison of vesicular stomatitis virus defective interfering particle synthesis in chick embryo and L cells.", "content": "A comparison of the ability of vesicular stomatitis virus (VSV) to generate and replicate defective interfering (DI) particles in primary chick embryo (CE) and mouse L cells was investigated as a means of analyzing host control over DI-particle synthesis and interfering capacity. Serial undiluted passage of VSV in CE and L cells indicate that VSV-DI particles are generated and (or) replicate with greater efficiency in CE than in L cells. When DI particles accumulate in L cells, they are able to interfere with infectious particle replication. The DI particles from CE cells interfered to the same extent with infectious particle replication in both CE and L cells. L cells, therefore, are not considered 'low-interference' hosts in which DI particles are produced and do not interfere with infectious virus replication, but rather hosts which restrict the production of DI particles.", "contents": "Comparison of vesicular stomatitis virus defective interfering particle synthesis in chick embryo and L cells. A comparison of the ability of vesicular stomatitis virus (VSV) to generate and replicate defective interfering (DI) particles in primary chick embryo (CE) and mouse L cells was investigated as a means of analyzing host control over DI-particle synthesis and interfering capacity. Serial undiluted passage of VSV in CE and L cells indicate that VSV-DI particles are generated and (or) replicate with greater efficiency in CE than in L cells. When DI particles accumulate in L cells, they are able to interfere with infectious particle replication. The DI particles from CE cells interfered to the same extent with infectious particle replication in both CE and L cells. L cells, therefore, are not considered 'low-interference' hosts in which DI particles are produced and do not interfere with infectious virus replication, but rather hosts which restrict the production of DI particles."}
{"id": "PMID:184897", "title": "Long-term cultures of chick embryo fibroblasts transformed by the Schmidt-Ruppin strain (D) of Rous sarcoma virus.", "content": "Attempts have been made to keep in vitro, for extended periods of time, cultures of chick embryo fibroblasts transformed by the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup D. Roller cultures of transformed chick cells kept in serum-deficient medium can be maintained without subcultivation for up to 6 months. The confluent cultures continuously release viruses and viable tumor cells into the medium. The released cells can be plated and have characteristics of growth and morphology which are relatively stable with time until the culture degenerates. Cells released at later stages of the culture produced substantially more viruses than those released earlier, suggesting that cell selection or differentiation occurs during long-term cultivation in low serum concentration. Long-term cultures of untransformed chick embryo fibroblasts can also be maintained in the same way. The release of viable cells by these confluent cultures, however, is negligible.", "contents": "Long-term cultures of chick embryo fibroblasts transformed by the Schmidt-Ruppin strain (D) of Rous sarcoma virus. Attempts have been made to keep in vitro, for extended periods of time, cultures of chick embryo fibroblasts transformed by the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup D. Roller cultures of transformed chick cells kept in serum-deficient medium can be maintained without subcultivation for up to 6 months. The confluent cultures continuously release viruses and viable tumor cells into the medium. The released cells can be plated and have characteristics of growth and morphology which are relatively stable with time until the culture degenerates. Cells released at later stages of the culture produced substantially more viruses than those released earlier, suggesting that cell selection or differentiation occurs during long-term cultivation in low serum concentration. Long-term cultures of untransformed chick embryo fibroblasts can also be maintained in the same way. The release of viable cells by these confluent cultures, however, is negligible."}
{"id": "PMID:184898", "title": "Lecithinase-negative variants of Clostridium perfringens; the identity of C. plagarum with C. perfringens.", "content": "Identity of Clostridium plagarum (Pr\u00e9vot) com. nov. (1938) with C. perfringens was demonstrated in the tests for the cultural and biochemical properties, DNA-DNA homology, susceptibility to C. perfringens-specific lysin, complementary synthesis of C. perfringens theta-toxin between C. plagarum and theta-toxin-negative mutants of C. perfringens, as well as the tests for gas-chromatographic patterns.", "contents": "Lecithinase-negative variants of Clostridium perfringens; the identity of C. plagarum with C. perfringens. Identity of Clostridium plagarum (Pr\u00e9vot) com. nov. (1938) with C. perfringens was demonstrated in the tests for the cultural and biochemical properties, DNA-DNA homology, susceptibility to C. perfringens-specific lysin, complementary synthesis of C. perfringens theta-toxin between C. plagarum and theta-toxin-negative mutants of C. perfringens, as well as the tests for gas-chromatographic patterns."}
{"id": "PMID:184899", "title": "Lactate dehydrogenase from autotrophic and heterotrophic cells of the marine diatom Cylindrotheca fusiformis Reimann & Lewin.", "content": "Cultures of Cylindrotheca furisormis grown either autotrohpically or heterotrophically on lactate contained significant amounts of NAD-dependent L(+)-lactate dehydrogenase (EC 1.1.1.27). Polyacylamide gel electrophoresis of crude enzyme extracts revealed a single band which was indistinguishable between autotrohpic and heterotrohpic cells. The Km for lactate of partially purified preparations was lower under heterotrophic conditions. The specific activity in crude extracts was higher under autotrophic than heterotrophic conditions; it dropped precipitously when autotrophic cells were transferred to the dark, increasing again only in the presence of lactate. These and related observations suggest that this enzyme has at most only a minor role in the assimilation of lactate during heterotrophic growth on lactate.", "contents": "Lactate dehydrogenase from autotrophic and heterotrophic cells of the marine diatom Cylindrotheca fusiformis Reimann & Lewin. Cultures of Cylindrotheca furisormis grown either autotrohpically or heterotrophically on lactate contained significant amounts of NAD-dependent L(+)-lactate dehydrogenase (EC 1.1.1.27). Polyacylamide gel electrophoresis of crude enzyme extracts revealed a single band which was indistinguishable between autotrohpic and heterotrohpic cells. The Km for lactate of partially purified preparations was lower under heterotrophic conditions. The specific activity in crude extracts was higher under autotrophic than heterotrophic conditions; it dropped precipitously when autotrophic cells were transferred to the dark, increasing again only in the presence of lactate. These and related observations suggest that this enzyme has at most only a minor role in the assimilation of lactate during heterotrophic growth on lactate."}
{"id": "PMID:184900", "title": "Leakage of periplasmic enzymes from lipopolysaccharide-defective mutants of Salmonella typhimurium.", "content": "Mutants of Salmonella typhimurium with defects in the heptose region of the lipopolysaccharide (LPS) molecule (heptose-deficient, chemotype Re) leak periplasmic enzymes (acid phosphatase (EC 3.1.3.2), cyclic phosphodiesterase, ribonuclease I (EC 3.1.4.22), and phosphoglucose isomerase (EC 5.3.1.9) (PGI is at least partially periplasmic in E. coli and S. typhimurium; see below)) and do not leak an internal enzyme (glucose-6-phosphate dehydrogenase) into the growth medium. The extent of this leakage is markedly increased at higher temperature (42 degrees C). Leakage of periplasmic enzymes from the strains lacking units distal to heptose I in the LPS molecule (chemotype Rd2) occurs only at 42 degrees C, and not at 30 or 37 degrees C. The extent of leakage of these enzymes from smooth strain and mutants of other LPS chemotypes (Rc, Rd1) is not significant, and is not influenced by growth temperatures. The kinetics of leakage of periplasmic enzymes after shift to 42 degrees C in nutrient broth reveal an accelerated release into the medium from heptose-deficient strains of cyclic phosphodiesterase and ribonuclease I after 30 min at 42 degrees C, and phosphoglucose isomerase after 60 min at 42 degrees C; at 30 degrees C the rate of release of cyclic phosphodiesterase and ribonuclease I is relatively slower. After 60 min at 42 degrees C in nutrient broth, growth of these strains has either slowed down or stopped. In L-broth, which permits the growth of the heptose-deficient strain (SA1377) at 42 degrees C, leakage of cyclic phosphodiesterase and phosphoglucose isomerase occurs, whereas there is no detectable leakage of these enzymes from the isogenic smooth strain (SA1355). Thus, leakage of the periplasmic enzymes from the heptose-deficient strain occurs with or without growth. Mg2+ (0.75 mM), sodium chloride (50 mM), and sucrose (100 mM) in nutrient broth at 42 degrees C prevent the leakage of these enzymes. The shedding of LPS from the heptose-deficient as well as the smooth strains is enhanced by high temperature (42 degrees C), whereas considerable leakage of protein occurs only in the heptose-deficient strain at 42 degrees C and not in the smooth strain. The smooth and heptose-deficient strains are equally sensitive to osmotic shock although a significant proportion of acid phosphatase and cyclic phosphodiesterase activities from the heptose-deficient cells grown at 42 degrees C comes off in the Tris-NaCl wash step suggesting a rather loose attachment of these enzymes onto the cell surface.", "contents": "Leakage of periplasmic enzymes from lipopolysaccharide-defective mutants of Salmonella typhimurium. Mutants of Salmonella typhimurium with defects in the heptose region of the lipopolysaccharide (LPS) molecule (heptose-deficient, chemotype Re) leak periplasmic enzymes (acid phosphatase (EC 3.1.3.2), cyclic phosphodiesterase, ribonuclease I (EC 3.1.4.22), and phosphoglucose isomerase (EC 5.3.1.9) (PGI is at least partially periplasmic in E. coli and S. typhimurium; see below)) and do not leak an internal enzyme (glucose-6-phosphate dehydrogenase) into the growth medium. The extent of this leakage is markedly increased at higher temperature (42 degrees C). Leakage of periplasmic enzymes from the strains lacking units distal to heptose I in the LPS molecule (chemotype Rd2) occurs only at 42 degrees C, and not at 30 or 37 degrees C. The extent of leakage of these enzymes from smooth strain and mutants of other LPS chemotypes (Rc, Rd1) is not significant, and is not influenced by growth temperatures. The kinetics of leakage of periplasmic enzymes after shift to 42 degrees C in nutrient broth reveal an accelerated release into the medium from heptose-deficient strains of cyclic phosphodiesterase and ribonuclease I after 30 min at 42 degrees C, and phosphoglucose isomerase after 60 min at 42 degrees C; at 30 degrees C the rate of release of cyclic phosphodiesterase and ribonuclease I is relatively slower. After 60 min at 42 degrees C in nutrient broth, growth of these strains has either slowed down or stopped. In L-broth, which permits the growth of the heptose-deficient strain (SA1377) at 42 degrees C, leakage of cyclic phosphodiesterase and phosphoglucose isomerase occurs, whereas there is no detectable leakage of these enzymes from the isogenic smooth strain (SA1355). Thus, leakage of the periplasmic enzymes from the heptose-deficient strain occurs with or without growth. Mg2+ (0.75 mM), sodium chloride (50 mM), and sucrose (100 mM) in nutrient broth at 42 degrees C prevent the leakage of these enzymes. The shedding of LPS from the heptose-deficient as well as the smooth strains is enhanced by high temperature (42 degrees C), whereas considerable leakage of protein occurs only in the heptose-deficient strain at 42 degrees C and not in the smooth strain. The smooth and heptose-deficient strains are equally sensitive to osmotic shock although a significant proportion of acid phosphatase and cyclic phosphodiesterase activities from the heptose-deficient cells grown at 42 degrees C comes off in the Tris-NaCl wash step suggesting a rather loose attachment of these enzymes onto the cell surface."}
{"id": "PMID:184901", "title": "Comparison of four eluents in the recovery of indigenous viruses from raw sludge.", "content": "The efficiency of 3% casein hydrolysate (CH), 3% lactalbumin hydrolysate (LH), 3% beef extract (BE), and 10% fetal calf serum (FCS) was compared for the recovery of viruses from raw sludge. CH and LH proved to be inefficient and were eliminated from the study after initial testing. In tests with 20 different samples of raw sludge, beef extract eluted virus in 15 (75%) and FCS revealed virus in 19 (95%) of the samples using BS-C-1 cells. That different eluents were not eluting different viruses from the same sample was shown by the serologic and electron-microscopic examination of 43% (18/42) of the isolates. The identified viruses included members of the entero- (coxsackie B, and polio) and reo-virus groups.", "contents": "Comparison of four eluents in the recovery of indigenous viruses from raw sludge. The efficiency of 3% casein hydrolysate (CH), 3% lactalbumin hydrolysate (LH), 3% beef extract (BE), and 10% fetal calf serum (FCS) was compared for the recovery of viruses from raw sludge. CH and LH proved to be inefficient and were eliminated from the study after initial testing. In tests with 20 different samples of raw sludge, beef extract eluted virus in 15 (75%) and FCS revealed virus in 19 (95%) of the samples using BS-C-1 cells. That different eluents were not eluting different viruses from the same sample was shown by the serologic and electron-microscopic examination of 43% (18/42) of the isolates. The identified viruses included members of the entero- (coxsackie B, and polio) and reo-virus groups."}
{"id": "PMID:184902", "title": "A comparison of the prophylactic and therapeutic effects of poly I:C and endotoxin in mice infected with Mengo virus.", "content": "We have compared the protective effect in AKR mice of poly I:C and bacterial endotoxins against lethal doses of Mengo virus. Administered intravenously or intraperitoneally, both interferon inducers protected mice to about the same extent from virus challenges of 2-3 LD50's. Endotoxin, however, was unable to protect the mice effectively against higher challenge doses of virus. Evidence is presented that the level of protection afforded by both inducers is related to the level of circulating interferon produced. We have also shown that a single intravenous dose of poly I:C results in the appearance of two distinct bursts of interferon activity, with maxima at about 2 h and 9 h post injection. Endotoxin, on the other hand, produced only one peak of activity, at 2 h post injection.", "contents": "A comparison of the prophylactic and therapeutic effects of poly I:C and endotoxin in mice infected with Mengo virus. We have compared the protective effect in AKR mice of poly I:C and bacterial endotoxins against lethal doses of Mengo virus. Administered intravenously or intraperitoneally, both interferon inducers protected mice to about the same extent from virus challenges of 2-3 LD50's. Endotoxin, however, was unable to protect the mice effectively against higher challenge doses of virus. Evidence is presented that the level of protection afforded by both inducers is related to the level of circulating interferon produced. We have also shown that a single intravenous dose of poly I:C results in the appearance of two distinct bursts of interferon activity, with maxima at about 2 h and 9 h post injection. Endotoxin, on the other hand, produced only one peak of activity, at 2 h post injection."}
{"id": "PMID:184903", "title": "Polymorph-mediated antibody-dependent cytoxicity--modulation of activity by drugs and immune interferon.", "content": "Bovine polymorphonuclear leukocytes (PMN) mediated antibody-dependent cell cytotoxicity (ADCC) against erythrocyte and herpes virus-infected target cells. The extent of cytotoxicity was not affected by drugs that inhibited DNA, RNA, or protein synthesis. The effect did not occur in the absence of divalent cations, was suppressed by pretreatment of PMN with silica and cytochalasin B, and was subject to the bidirectional control by cyclic nucleotides; drugs decreasing cyclic AMP or elevating cyclic GMP levels enhanced ADCC. The ADCC phenomena was also enhanced by supernates containing immune interferon activity from antigen-stimulated-immune lymphocyte-macrophage cultures. The possibility that immune interferon(s) might be causing the elevation of ADCC and the relevance of this observation in terms of the part interferon might play in modulating recovery from herpes virus infections was discussed.", "contents": "Polymorph-mediated antibody-dependent cytoxicity--modulation of activity by drugs and immune interferon. Bovine polymorphonuclear leukocytes (PMN) mediated antibody-dependent cell cytotoxicity (ADCC) against erythrocyte and herpes virus-infected target cells. The extent of cytotoxicity was not affected by drugs that inhibited DNA, RNA, or protein synthesis. The effect did not occur in the absence of divalent cations, was suppressed by pretreatment of PMN with silica and cytochalasin B, and was subject to the bidirectional control by cyclic nucleotides; drugs decreasing cyclic AMP or elevating cyclic GMP levels enhanced ADCC. The ADCC phenomena was also enhanced by supernates containing immune interferon activity from antigen-stimulated-immune lymphocyte-macrophage cultures. The possibility that immune interferon(s) might be causing the elevation of ADCC and the relevance of this observation in terms of the part interferon might play in modulating recovery from herpes virus infections was discussed."}
{"id": "PMID:184904", "title": "Indirect microhemagglutination test for varicella--zoster antibody determination.", "content": "An indirect microhemagglutination assay (IHA) was devised because of a need to provide an alternative test to complement fixation (CF) for varicella-zoster (V-Z) antibody determination. Human erythrocytes were sequentially treated with 2% glutaraldehyde, 0.04% tannic acid, and 2% pyruvic aldehyde then exposed to sonicated V-Z infected cells. This same tanning procedure was suitable for herpes simplex and Epstein-Barr virus antigen attachment but unsatisfactory for several non-herpes-group viruses. V-Z antibody titres determined by IHA were generally 2 to 6 times higher than CF titres. Cross-reaction with herpes simplex antibody was minimal.", "contents": "Indirect microhemagglutination test for varicella--zoster antibody determination. An indirect microhemagglutination assay (IHA) was devised because of a need to provide an alternative test to complement fixation (CF) for varicella-zoster (V-Z) antibody determination. Human erythrocytes were sequentially treated with 2% glutaraldehyde, 0.04% tannic acid, and 2% pyruvic aldehyde then exposed to sonicated V-Z infected cells. This same tanning procedure was suitable for herpes simplex and Epstein-Barr virus antigen attachment but unsatisfactory for several non-herpes-group viruses. V-Z antibody titres determined by IHA were generally 2 to 6 times higher than CF titres. Cross-reaction with herpes simplex antibody was minimal."}
{"id": "PMID:184905", "title": "Temperature-sensitive mutants of vesicular stomatitis virus: viral RNA synthesis in cells infected with mutants belonging to complementation group I.", "content": "The RNA polymerase in cells infected with three group I mutants of vesicular stomatitis virus has been examined. Mouse L cells were incubated at the permissive temperature (30 degrees C) for a few hours after infection to allow the development of secondary transcription. The temperature dependence of the secondary transcription system was determined from the incorporation of labelled uridine, in the presence of cycloheximide, at 30 and at 38 degrees C, the later temperature being non-permissive for viral replication. In cells infected with mutants W14, W28, and G11 at a low multiplicity (20 PFU/cells) secondary transcriptase activity was markedly temperature-sensitive after 3 and 5 h of infection at 30 degrees C. At a high multiplicity of infection (1000 PFU/cell) cells infected with W28 showed considerable RNA synthesis at 38 degrees C after 3 h at 30 degrees C. RNA synthesis was also observed in W28-infected cells in which protein synthesis was allowed to continue after the shift from 30 to 38 degrees C. In the latter two cases the RNA synthesized contained 12-18S species but little or no 30S mRNA.", "contents": "Temperature-sensitive mutants of vesicular stomatitis virus: viral RNA synthesis in cells infected with mutants belonging to complementation group I. The RNA polymerase in cells infected with three group I mutants of vesicular stomatitis virus has been examined. Mouse L cells were incubated at the permissive temperature (30 degrees C) for a few hours after infection to allow the development of secondary transcription. The temperature dependence of the secondary transcription system was determined from the incorporation of labelled uridine, in the presence of cycloheximide, at 30 and at 38 degrees C, the later temperature being non-permissive for viral replication. In cells infected with mutants W14, W28, and G11 at a low multiplicity (20 PFU/cells) secondary transcriptase activity was markedly temperature-sensitive after 3 and 5 h of infection at 30 degrees C. At a high multiplicity of infection (1000 PFU/cell) cells infected with W28 showed considerable RNA synthesis at 38 degrees C after 3 h at 30 degrees C. RNA synthesis was also observed in W28-infected cells in which protein synthesis was allowed to continue after the shift from 30 to 38 degrees C. In the latter two cases the RNA synthesized contained 12-18S species but little or no 30S mRNA."}
{"id": "PMID:184906", "title": "Pathways of glucose catabolism in Mycobacterium smegmatis.", "content": "Glucose metabolism in Mycobacterium smegmatis was investigated by the radiorespirometric method and by assaying for key enzymes of the major energy-yielding pathways. Glucose is oxidized in this organism mainly through the Embden-Meyerhof-Parnas pathway, irrespective of the carbon source used for growth. The pentose phosphate pathway plays only a minor role and its extent depends on the carbon source used for growth. Enzymes of glycolytic and oxidative pathways were detected in cells grown on glucose, glycerol, or pyruvate but enzymes of the Entner-Duodroff pathway could be detected only in glucose-grown cells. Labeled acetate is utilized by cells cultured on glucose, glycerol, and pyruvate. In all cases more of C1 of acetate was converted to CO2 while incorporation into cellular constituents was maximum from C2 of acetate.", "contents": "Pathways of glucose catabolism in Mycobacterium smegmatis. Glucose metabolism in Mycobacterium smegmatis was investigated by the radiorespirometric method and by assaying for key enzymes of the major energy-yielding pathways. Glucose is oxidized in this organism mainly through the Embden-Meyerhof-Parnas pathway, irrespective of the carbon source used for growth. The pentose phosphate pathway plays only a minor role and its extent depends on the carbon source used for growth. Enzymes of glycolytic and oxidative pathways were detected in cells grown on glucose, glycerol, or pyruvate but enzymes of the Entner-Duodroff pathway could be detected only in glucose-grown cells. Labeled acetate is utilized by cells cultured on glucose, glycerol, and pyruvate. In all cases more of C1 of acetate was converted to CO2 while incorporation into cellular constituents was maximum from C2 of acetate."}
{"id": "PMID:184907", "title": "Anomalous aggregation of Clostridium perfringens enterotoxin under dissociating conditions.", "content": "Polyacrylamide gel electrophoresis of highly purified Clostridium perfringens enterotoxin revealed electrophoretic microheterogeneity of the enterotoxin, apparently because of slight charge differences in the peptides. Detergent gel electrophoresis showed that purified enterotoxin formed high molecular weight aggregates in the presence of both sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide. No conditions capable of inhibiting this phenomenon were found. Although a molecular weight of 35 000 daltons has been reported in the literature, the experimentally determined molecular weight values in the presence of detergents corresponded to multiples of a theoretical subunit molecular weight of 17 500 daltons. Binding studies performed by equilibrium dialysis and ultracentrifugation methods revealed that the enterotoxin bound very small amounts of SDS per gram of protein. The evidence presented indicates possible detergent induced structural alterations of the protein.", "contents": "Anomalous aggregation of Clostridium perfringens enterotoxin under dissociating conditions. Polyacrylamide gel electrophoresis of highly purified Clostridium perfringens enterotoxin revealed electrophoretic microheterogeneity of the enterotoxin, apparently because of slight charge differences in the peptides. Detergent gel electrophoresis showed that purified enterotoxin formed high molecular weight aggregates in the presence of both sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide. No conditions capable of inhibiting this phenomenon were found. Although a molecular weight of 35 000 daltons has been reported in the literature, the experimentally determined molecular weight values in the presence of detergents corresponded to multiples of a theoretical subunit molecular weight of 17 500 daltons. Binding studies performed by equilibrium dialysis and ultracentrifugation methods revealed that the enterotoxin bound very small amounts of SDS per gram of protein. The evidence presented indicates possible detergent induced structural alterations of the protein."}
{"id": "PMID:184908", "title": "Liver transplantation in a patient with cholangiocarcinoma and ulcerative colitis.", "content": "A 39 year-old patient with cholangiocarcinoma and pre-existing ulcerative colitis was successfully treated by orthotopic liver transplantation. He was given low doses of prednisone and azathioprine and survived for more than 9 months, dying with tumour metastases, thrombosis of the inferior vena cava and an intra-abdominal abscess. At autopsy the homograft showed little evidence of rejection. Preoperatively the patient had septicemia. Removal of his liver was difficult. The discrepancy between donor and recipient in size of blood vessels and the presence of two hepatic arteries in the donor caused problems during the vascular anastomoses. During the operation cardiac arrest occurred. Postoperatively there were several medical and surgical problems, including intraperitoneal and gastrointestinal hemorrhage, paralysis of the right dome of the diaphragm, sinus bradycardia, massive diuresis, peroneal nerve palsy, and one major and three minor episodes of rejection, which were reversed by giving pulse doses of methylprednisolone intravenously.", "contents": "Liver transplantation in a patient with cholangiocarcinoma and ulcerative colitis. A 39 year-old patient with cholangiocarcinoma and pre-existing ulcerative colitis was successfully treated by orthotopic liver transplantation. He was given low doses of prednisone and azathioprine and survived for more than 9 months, dying with tumour metastases, thrombosis of the inferior vena cava and an intra-abdominal abscess. At autopsy the homograft showed little evidence of rejection. Preoperatively the patient had septicemia. Removal of his liver was difficult. The discrepancy between donor and recipient in size of blood vessels and the presence of two hepatic arteries in the donor caused problems during the vascular anastomoses. During the operation cardiac arrest occurred. Postoperatively there were several medical and surgical problems, including intraperitoneal and gastrointestinal hemorrhage, paralysis of the right dome of the diaphragm, sinus bradycardia, massive diuresis, peroneal nerve palsy, and one major and three minor episodes of rejection, which were reversed by giving pulse doses of methylprednisolone intravenously."}
{"id": "PMID:184909", "title": "Primary hyperlipoproteinemia in childhood and adolescence: identification and treatment of persons at risk for premature atherosclerosis.", "content": "Determination of serum cholesterol values in three populations of children and adolescents, totalling 4013 subjects aged 1 month to 20 years, revealed 16 cases of primary hyperbetalipoproteinemia (overall frequency, 1:251) and led to the detection of the disorder in 12 asymptomatic siblings. The upper limit of normal for serum cholesterol concentration was approximately 200 mg/dl at all ages studied. Dietary treatment was instituted in patients whose serum cholesterol value exceeded this limit and in whom a primary lipid defect was confirmed; the serum cholesterol value decreased in all patients who adhered to the diet. However, since the potential hazards and long-term results of dietary treatment, with or without drug therapy, in growing children are not known, such treatment should be reserved for affected children with a family history of premature atherosclerosis, and follow-up is essential.", "contents": "Primary hyperlipoproteinemia in childhood and adolescence: identification and treatment of persons at risk for premature atherosclerosis. Determination of serum cholesterol values in three populations of children and adolescents, totalling 4013 subjects aged 1 month to 20 years, revealed 16 cases of primary hyperbetalipoproteinemia (overall frequency, 1:251) and led to the detection of the disorder in 12 asymptomatic siblings. The upper limit of normal for serum cholesterol concentration was approximately 200 mg/dl at all ages studied. Dietary treatment was instituted in patients whose serum cholesterol value exceeded this limit and in whom a primary lipid defect was confirmed; the serum cholesterol value decreased in all patients who adhered to the diet. However, since the potential hazards and long-term results of dietary treatment, with or without drug therapy, in growing children are not known, such treatment should be reserved for affected children with a family history of premature atherosclerosis, and follow-up is essential."}
{"id": "PMID:184911", "title": "Cushing's disease in a child with lymphosarcoma and acute leukemia.", "content": "A 6-year-old girl with lymphosarcoma developed Cushing's syndrome. Suppression-stimulation studies verified adrenal hyperfunction secondary to bilateral adrenocortical hyperplasia, and the course suggested the possibility of \"ectopic ACTH\" production by the neoplasm as the etiology.", "contents": "Cushing's disease in a child with lymphosarcoma and acute leukemia. A 6-year-old girl with lymphosarcoma developed Cushing's syndrome. Suppression-stimulation studies verified adrenal hyperfunction secondary to bilateral adrenocortical hyperplasia, and the course suggested the possibility of \"ectopic ACTH\" production by the neoplasm as the etiology."}
{"id": "PMID:184912", "title": "The treatment of Wilms' tumor: Results of the national Wilms' tumor study.", "content": "The National Wilms' Tumor Study, initiated in 1969, tested competing treatment strategems for patients with tumors ranging from Group (Gp) I (tumors confined to the kidney and totally removed) to Gp IV (remote metastases present at diagnosis). Three hundred and fifty-nine of 606 registered patients were randomized in the trial. Gp I patients under 2 years of age fared well whether postoperative radiation therapy (RT) was or was not added to 15 months' maintenance actinomycin D (AMD). Their prognosis was better than that for older cohorts similarly treated, in whom the difference in relapse rates between treatment groups were suggestive of an RT effect. Combined AMD and vincristine (VCR) gave better results than either agent alone in patients with more advanced tumors (Gps II and III) still confined to the abdomen, all of whom received postoperative RT as well. Preoperative VCR given Gp IV patients in addition to postoperative RT, AMD, and VCR did not improve results. The frequency of mesoblastic nephroma (1%), of bilateral tumors (5%), and of incorrect preoperative diagnosis of Wilms' tumor (5%), the toxicities of the various regimens, and other ancillary data are presented and discussed.", "contents": "The treatment of Wilms' tumor: Results of the national Wilms' tumor study. The National Wilms' Tumor Study, initiated in 1969, tested competing treatment strategems for patients with tumors ranging from Group (Gp) I (tumors confined to the kidney and totally removed) to Gp IV (remote metastases present at diagnosis). Three hundred and fifty-nine of 606 registered patients were randomized in the trial. Gp I patients under 2 years of age fared well whether postoperative radiation therapy (RT) was or was not added to 15 months' maintenance actinomycin D (AMD). Their prognosis was better than that for older cohorts similarly treated, in whom the difference in relapse rates between treatment groups were suggestive of an RT effect. Combined AMD and vincristine (VCR) gave better results than either agent alone in patients with more advanced tumors (Gps II and III) still confined to the abdomen, all of whom received postoperative RT as well. Preoperative VCR given Gp IV patients in addition to postoperative RT, AMD, and VCR did not improve results. The frequency of mesoblastic nephroma (1%), of bilateral tumors (5%), and of incorrect preoperative diagnosis of Wilms' tumor (5%), the toxicities of the various regimens, and other ancillary data are presented and discussed."}
{"id": "PMID:184913", "title": "Preoperative versus postoperative radiotherapy, single versus multiple courses of actinomycin D, in the treatment of Wilms' tumor. Preliminary results of a controlled clinical trial conducted by the International Society of Paediatric Oncology (S.I.O.P.).", "content": "The preliminary results of a controlled clinical trial organized by the S.I.O.P. of radiotherapy and chemotherapy in patients with nephroblastoma are presented. Forty-two centers have participated. Between September 1971 and October 1974, 398 patients were registered; 195 were eligible for the trial and were randomized. The remaining 203 patients were excluded from the trial, but were followed in the same way as the patients in the trial. The results were evaluated in terms of recurrence-free survival rate and survival rate. Results in patients who received preoperative and postoperative radiotherapy (group A, 73 patients) were compared with the results in patients who recieved only postoperative radiotherapy (group B, 64 patients). The tumor ruptured at surgery in three patients of group A, and in 20 patients of group B, a difference that is statistically significant. No significant difference in survival and recurrence-free survival between groups A and B is observed at present. Results in patients treated with a single course of actinomycin D (group I, 80 patients) were compared with the results in patients treated with multiple courses (group II, 80 patients). At present, no significant difference is found between the two groups.", "contents": "Preoperative versus postoperative radiotherapy, single versus multiple courses of actinomycin D, in the treatment of Wilms' tumor. Preliminary results of a controlled clinical trial conducted by the International Society of Paediatric Oncology (S.I.O.P.). The preliminary results of a controlled clinical trial organized by the S.I.O.P. of radiotherapy and chemotherapy in patients with nephroblastoma are presented. Forty-two centers have participated. Between September 1971 and October 1974, 398 patients were registered; 195 were eligible for the trial and were randomized. The remaining 203 patients were excluded from the trial, but were followed in the same way as the patients in the trial. The results were evaluated in terms of recurrence-free survival rate and survival rate. Results in patients who received preoperative and postoperative radiotherapy (group A, 73 patients) were compared with the results in patients who recieved only postoperative radiotherapy (group B, 64 patients). The tumor ruptured at surgery in three patients of group A, and in 20 patients of group B, a difference that is statistically significant. No significant difference in survival and recurrence-free survival between groups A and B is observed at present. Results in patients treated with a single course of actinomycin D (group I, 80 patients) were compared with the results in patients treated with multiple courses (group II, 80 patients). At present, no significant difference is found between the two groups."}
{"id": "PMID:184914", "title": "Distribution of adenosine triphosphatase in infiltrating ductal carcinoma and non-neoplastic breast.", "content": "The histochemical reaction for adenosine triphosphatase (ATPase) has previously been used to differentiate myoepithelial from epithelial cells in the breast and to investigate the possible contribution of myoepithelial cells to mammary carcinoma. Discrepancies in published reports prompted this study of ATPase in non-neoplastic breast and infiltrating ductal carcinoma. ATPase was localized mainly on myoepithelial cells of normal breast and was identified with significant frequency on epithelial cells in hyperplastic ducts. Infiltrating ductal carcinomas usually displayed a variable reactivity. In one instance, malignant cells demonstrating mucin production were found to be ATPase-positive. An infiltrating ductal carcinoma of the papillary type with apocrine features was also strongly ATPase-reactive. It is concluded that ATPase is not an exclusive marker of myoepithelial cells and, therefore, data resulting from the use of this enzyme to study the role of the myoepithelium in mammary carcinoma must be interpreted with caution.", "contents": "Distribution of adenosine triphosphatase in infiltrating ductal carcinoma and non-neoplastic breast. The histochemical reaction for adenosine triphosphatase (ATPase) has previously been used to differentiate myoepithelial from epithelial cells in the breast and to investigate the possible contribution of myoepithelial cells to mammary carcinoma. Discrepancies in published reports prompted this study of ATPase in non-neoplastic breast and infiltrating ductal carcinoma. ATPase was localized mainly on myoepithelial cells of normal breast and was identified with significant frequency on epithelial cells in hyperplastic ducts. Infiltrating ductal carcinomas usually displayed a variable reactivity. In one instance, malignant cells demonstrating mucin production were found to be ATPase-positive. An infiltrating ductal carcinoma of the papillary type with apocrine features was also strongly ATPase-reactive. It is concluded that ATPase is not an exclusive marker of myoepithelial cells and, therefore, data resulting from the use of this enzyme to study the role of the myoepithelium in mammary carcinoma must be interpreted with caution."}
{"id": "PMID:184915", "title": "Primary liver cell carcinoma in the presence or absence of hepatitis B antigen.", "content": "The clinical course and pathological patterns of a group of 13 patients with both primary liver cell carcinoma and Hepatitis B surface antigen (HBsAg) are described and contrasted with those of 43 patients with primary liver cell carcinoma but without HBsAg. HBsAg-positive carcinoma patients demonstrated a higher incidence of splenomegaly, transudative ascites, and the presence of alpha-fetoprotein, although none of these reached statistical significance. Serum bilirubin was significantly higher in patients with HBsAg. HBsAg-positive carcinoma patients most frequently originated from countries where the presence of HBsAg is high in the general population. Survival time from the diagnosis of primary liver cell carcinoma was shorter in patients with HBsAg.", "contents": "Primary liver cell carcinoma in the presence or absence of hepatitis B antigen. The clinical course and pathological patterns of a group of 13 patients with both primary liver cell carcinoma and Hepatitis B surface antigen (HBsAg) are described and contrasted with those of 43 patients with primary liver cell carcinoma but without HBsAg. HBsAg-positive carcinoma patients demonstrated a higher incidence of splenomegaly, transudative ascites, and the presence of alpha-fetoprotein, although none of these reached statistical significance. Serum bilirubin was significantly higher in patients with HBsAg. HBsAg-positive carcinoma patients most frequently originated from countries where the presence of HBsAg is high in the general population. Survival time from the diagnosis of primary liver cell carcinoma was shorter in patients with HBsAg."}
{"id": "PMID:184916", "title": "Effect of prostaglandins on adenylate cyclase activities in membranes from liver and transplantable hepatomas.", "content": "The effects of prostaglandins on adenylate cyclase activity have been examined in membranes purified from normal rat liver and from a series of Morris hepatomas. Prostaglandin E1 gave the greatest stimulation (up to two-fold) in all membranes. However, prostaglandins A1, A2, and F2alpha, although stimulatory in liver and four tumor membranes, were inhibitory of adenylate cyclase activity in membranes from two of the fast-growing tumors. Arrhenius plots yielded broken line curves (at 20 degrees C) for the basal activity of all enzymes. Addition of various prostaglandins caused shifts in the broken line curves and/or produced nonbroken (straight) line curves for the liver and many of the hepatoma adenylate cyclases.", "contents": "Effect of prostaglandins on adenylate cyclase activities in membranes from liver and transplantable hepatomas. The effects of prostaglandins on adenylate cyclase activity have been examined in membranes purified from normal rat liver and from a series of Morris hepatomas. Prostaglandin E1 gave the greatest stimulation (up to two-fold) in all membranes. However, prostaglandins A1, A2, and F2alpha, although stimulatory in liver and four tumor membranes, were inhibitory of adenylate cyclase activity in membranes from two of the fast-growing tumors. Arrhenius plots yielded broken line curves (at 20 degrees C) for the basal activity of all enzymes. Addition of various prostaglandins caused shifts in the broken line curves and/or produced nonbroken (straight) line curves for the liver and many of the hepatoma adenylate cyclases."}
{"id": "PMID:184917", "title": "A relative deficiency of cytochrome P-450 and aryl hydrocarbon [benzo(a)pyrene] hydroxylase in hyperplastic nodules induced by 2-acetylaminofluorene in rat liver.", "content": "The concentrations of cytochrome P-450 and the activities of aryl hydrocarbon [benzo(a)pyrene] hydroxylase (AHH) and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase were measured in early (gray-white) and remodeled (brown) hyperplastic nodules induced in the livers of rats with 2-acetylaminofluorene and were compared to the values in control livers and in the liver surrounding the nodules. Cytochrome P-450 content of early (14 weeks) hyperplastic nodules is 30% of the activity of untreated control livers and 48% of the activity of the surrounding liver. AHH activity of the  early nodules is 10% of the control activity and 33% of the activity in the surrounding nonnodular liver. Nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity in the microsomes of early nodules is 76% of the control activity and 78% of the activity in the surrounding liver. In the late remodeled nodules, (22 and 25 weeks), the cytochrome P-450 content is 40% of that of controls and AHH activity is 15% of the control activity. In primary hepatomas induced by 2-acetylaminofluorene, cytochrome P-450 content is 21% of that of controls, AHH activity is 11% of the activity of controls, and reductase is 50% of the control activity. These results, indicating a relative nodule deficiency in some of the cellular components believed to be important in the activation of hepatocarcinogens and hepatotoxins, offer one possible explanation for the relative resistance to carcinogen cytotoxicity of hyperplastic liver nodules.", "contents": "A relative deficiency of cytochrome P-450 and aryl hydrocarbon [benzo(a)pyrene] hydroxylase in hyperplastic nodules induced by 2-acetylaminofluorene in rat liver. The concentrations of cytochrome P-450 and the activities of aryl hydrocarbon [benzo(a)pyrene] hydroxylase (AHH) and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase were measured in early (gray-white) and remodeled (brown) hyperplastic nodules induced in the livers of rats with 2-acetylaminofluorene and were compared to the values in control livers and in the liver surrounding the nodules. Cytochrome P-450 content of early (14 weeks) hyperplastic nodules is 30% of the activity of untreated control livers and 48% of the activity of the surrounding liver. AHH activity of the  early nodules is 10% of the control activity and 33% of the activity in the surrounding nonnodular liver. Nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity in the microsomes of early nodules is 76% of the control activity and 78% of the activity in the surrounding liver. In the late remodeled nodules, (22 and 25 weeks), the cytochrome P-450 content is 40% of that of controls and AHH activity is 15% of the control activity. In primary hepatomas induced by 2-acetylaminofluorene, cytochrome P-450 content is 21% of that of controls, AHH activity is 11% of the activity of controls, and reductase is 50% of the control activity. These results, indicating a relative nodule deficiency in some of the cellular components believed to be important in the activation of hepatocarcinogens and hepatotoxins, offer one possible explanation for the relative resistance to carcinogen cytotoxicity of hyperplastic liver nodules."}
{"id": "PMID:184918", "title": "Virus-infected avian cell lines established in vitro.", "content": "Four virus-infected avian cell lines have been established in culture. Two of these lines, infected with BAI strain A virus, liberate only small quantities of virus in the culture fluid. The cells retain the ability to induce myeloblastic leukemia when inoculated i.v. into 1- to 2-day-old chicks, but do so less efficiently than freshly obtained myeloblasts. These cells do not appear to be transplantable, since the disease produced is characterized by the presence of myeloblasts that liberate large quantities of virus. The other two cell lines, infected with the MC29 strain of avian leukosis virus, liberate normal levels of infectious virus in the culture fluid. When these cells are inoculated into the wing web of 1- to 2-day-old chicks, tumors develop at the site of inoculation which are detectable as early as 4 to 7 days after challenge. Chromosome studies demonstrate that the four cell lines have karyotypes typical of Gallus domesticus. The myeloblastic cell lines (D.U. 11157 and D.U. 1765) show a reduction in the number of microchromosomes. These cell lines have been carried in continuous culture for various lengths of time, can be frozen, are easily recovered in viable form, and appear to be capable of indefinite growth.", "contents": "Virus-infected avian cell lines established in vitro. Four virus-infected avian cell lines have been established in culture. Two of these lines, infected with BAI strain A virus, liberate only small quantities of virus in the culture fluid. The cells retain the ability to induce myeloblastic leukemia when inoculated i.v. into 1- to 2-day-old chicks, but do so less efficiently than freshly obtained myeloblasts. These cells do not appear to be transplantable, since the disease produced is characterized by the presence of myeloblasts that liberate large quantities of virus. The other two cell lines, infected with the MC29 strain of avian leukosis virus, liberate normal levels of infectious virus in the culture fluid. When these cells are inoculated into the wing web of 1- to 2-day-old chicks, tumors develop at the site of inoculation which are detectable as early as 4 to 7 days after challenge. Chromosome studies demonstrate that the four cell lines have karyotypes typical of Gallus domesticus. The myeloblastic cell lines (D.U. 11157 and D.U. 1765) show a reduction in the number of microchromosomes. These cell lines have been carried in continuous culture for various lengths of time, can be frozen, are easily recovered in viable form, and appear to be capable of indefinite growth."}
{"id": "PMID:184919", "title": "Prolactin receptors in 7,12-dimethylbenz(a) anthracene-induced mammary tumors following endocrine ablation.", "content": "We have determined the effect of ovariectomy and hypophysectomy on prolactin receptors in 7,12-dimethylbenz(a)anthracene-induced mammary tumors. Growing tumors from intact rats show a wide range in the number of prolactin receptors. Ovariectomy causes a slight (approximately 30%) decrease in receptors regardless of whether tumors regress or continue to grow, while the affinity of the receptor for prolactin remains unchanged. Hypophysectomy, which causes a prompt 10-fold decrease in prolactin receptors in rat liver, causes only a slight reduction in prolactin receptors in tumors from these same animals. We conclude that autonomous and ovariectomy responsive 7,12-dimethylbenz(a)anthracene-induced mammary tumors cannot be distinguished on the basis of prolactin receptor sites and that endocrine regulation of prolactin receptors is distinctly different in normal liver and neoplastic mammary tissue.", "contents": "Prolactin receptors in 7,12-dimethylbenz(a) anthracene-induced mammary tumors following endocrine ablation. We have determined the effect of ovariectomy and hypophysectomy on prolactin receptors in 7,12-dimethylbenz(a)anthracene-induced mammary tumors. Growing tumors from intact rats show a wide range in the number of prolactin receptors. Ovariectomy causes a slight (approximately 30%) decrease in receptors regardless of whether tumors regress or continue to grow, while the affinity of the receptor for prolactin remains unchanged. Hypophysectomy, which causes a prompt 10-fold decrease in prolactin receptors in rat liver, causes only a slight reduction in prolactin receptors in tumors from these same animals. We conclude that autonomous and ovariectomy responsive 7,12-dimethylbenz(a)anthracene-induced mammary tumors cannot be distinguished on the basis of prolactin receptor sites and that endocrine regulation of prolactin receptors is distinctly different in normal liver and neoplastic mammary tissue."}
{"id": "PMID:184920", "title": "Cyclic adenosine 3':5'-monophosphate phosphodiesterase activity in normal and chronic lymphocytic leukemia lymphocytes.", "content": "The specific activity of cyclic adenosine 3':5'-monophosphate phosphodiesterase was measured in lymphocytes isolated from the blood of normal subjects, from patients with chronic lymphocytic leukemia, and from tonsil tissue. The mean specific activity of cyclic adenosine 3':5'-monophosphate phosphodiesterase in the lymphocytes from patients with untreated chronic lymphocytic leukemia was lower than that in lymphocytes from the blood of normal subjects or from tonsils. Cyclic adenosine 3':5'-monophosphate phosphodiesterase levels did not correlate with differences in B- and T-cell lymphocyte subpopulations or with peripheral blood lymphocyte counts.", "contents": "Cyclic adenosine 3':5'-monophosphate phosphodiesterase activity in normal and chronic lymphocytic leukemia lymphocytes. The specific activity of cyclic adenosine 3':5'-monophosphate phosphodiesterase was measured in lymphocytes isolated from the blood of normal subjects, from patients with chronic lymphocytic leukemia, and from tonsil tissue. The mean specific activity of cyclic adenosine 3':5'-monophosphate phosphodiesterase in the lymphocytes from patients with untreated chronic lymphocytic leukemia was lower than that in lymphocytes from the blood of normal subjects or from tonsils. Cyclic adenosine 3':5'-monophosphate phosphodiesterase levels did not correlate with differences in B- and T-cell lymphocyte subpopulations or with peripheral blood lymphocyte counts."}
{"id": "PMID:184921", "title": "Histogenesis and Morphology of periosteal sarcomas induced by FBJ virus in NIH Swiss mice.", "content": "FBJ virus was injected i.p. into 145 neonatal NIH Swiss [N:NIH(s)] mice. Eighty mice developed a total of 110 neoplasms by 5 months of age. The mean latent period of the tumors was 71 days (26 to 145) postinjection. The frequency of occurrence of neoplasms at different sites was: diaphragm, 45%; ribs, 14%; vertebrae, 14%; femora, 9%; pelvic bones, 5%; tibiae, 4%; sternebrae, 3%; and inguinal area, 7%. The neoplasms were characterized histologically by elongated or rounded cells associated with an abundant connective tissue stroma. Occasional areas of bone formation and apparent osteoid metaplasia were seen. Bone tumors appeared to arise from periosteal cells, to grow by expansion, and to invade locally, but they failed to metastasize. Neoplasms of the diaphragm originated in the central aponeurosis and appeared histologically similar to bone neoplasms. Histochemical studies demonstrated abundant alkaline phosphatase in tumor cells, and ultrastructural observations revealed subcellular characteristics of osteoblasts and chondroblasts. Tumors were readily transplantable and had histopathological characteristics similar to those of the primary viral-induced tumors. The results of this study indicate that the FBJ virus induces in NIH Swiss mice a unique type of chondroosseous neoplasm derived from periosteal cells which has a resemblance to human juxtacortical (parosteal) osteosarcoma.", "contents": "Histogenesis and Morphology of periosteal sarcomas induced by FBJ virus in NIH Swiss mice. FBJ virus was injected i.p. into 145 neonatal NIH Swiss [N:NIH(s)] mice. Eighty mice developed a total of 110 neoplasms by 5 months of age. The mean latent period of the tumors was 71 days (26 to 145) postinjection. The frequency of occurrence of neoplasms at different sites was: diaphragm, 45%; ribs, 14%; vertebrae, 14%; femora, 9%; pelvic bones, 5%; tibiae, 4%; sternebrae, 3%; and inguinal area, 7%. The neoplasms were characterized histologically by elongated or rounded cells associated with an abundant connective tissue stroma. Occasional areas of bone formation and apparent osteoid metaplasia were seen. Bone tumors appeared to arise from periosteal cells, to grow by expansion, and to invade locally, but they failed to metastasize. Neoplasms of the diaphragm originated in the central aponeurosis and appeared histologically similar to bone neoplasms. Histochemical studies demonstrated abundant alkaline phosphatase in tumor cells, and ultrastructural observations revealed subcellular characteristics of osteoblasts and chondroblasts. Tumors were readily transplantable and had histopathological characteristics similar to those of the primary viral-induced tumors. The results of this study indicate that the FBJ virus induces in NIH Swiss mice a unique type of chondroosseous neoplasm derived from periosteal cells which has a resemblance to human juxtacortical (parosteal) osteosarcoma."}
{"id": "PMID:184922", "title": "Virus-dependent cytostatic activity to mammary tumor cells of lymphocytes from normal mice.", "content": "A cytostasis assay has been used to study the natural immunity of mice to murine mammary tumor virus (MTV). Spleen cells from adults of all strains tested were found to be cytostatic to a variety of MTV-positive mammary tumor cell lines. Newborn spleen cells were unreactive in the same cytostasis assay. The degree of reactivity to the target cells was greater in spleen cell preparations from low MTV expressors than from syngeneic, high MTV expressors. The cytostasis was specific, since MTV antigens prepared from gradient-purified whole MT virions significantly blocked the reaction. In addition, spleen cells were totally nonreactive to MTV-negative cell lines. Other types of lymphoid cells, such as lymph node cells as well as peritoneal macrophages, were highly cytostatic under similar conditions. Spleen cells from nude athymic donors were not cytostatic. Since depletion of splenic T-lymphocytes by use of anti-theta serum also did not significantly affect cytostasis, it was concluded that T-cells were required for initiation of immunity to MTV but that the effector cells were not theta positive. Blocking factors were found to exist in the sera of mammary tumor-bearing animals that prevented cytostasis by reactive spleen cells.", "contents": "Virus-dependent cytostatic activity to mammary tumor cells of lymphocytes from normal mice. A cytostasis assay has been used to study the natural immunity of mice to murine mammary tumor virus (MTV). Spleen cells from adults of all strains tested were found to be cytostatic to a variety of MTV-positive mammary tumor cell lines. Newborn spleen cells were unreactive in the same cytostasis assay. The degree of reactivity to the target cells was greater in spleen cell preparations from low MTV expressors than from syngeneic, high MTV expressors. The cytostasis was specific, since MTV antigens prepared from gradient-purified whole MT virions significantly blocked the reaction. In addition, spleen cells were totally nonreactive to MTV-negative cell lines. Other types of lymphoid cells, such as lymph node cells as well as peritoneal macrophages, were highly cytostatic under similar conditions. Spleen cells from nude athymic donors were not cytostatic. Since depletion of splenic T-lymphocytes by use of anti-theta serum also did not significantly affect cytostasis, it was concluded that T-cells were required for initiation of immunity to MTV but that the effector cells were not theta positive. Blocking factors were found to exist in the sera of mammary tumor-bearing animals that prevented cytostasis by reactive spleen cells."}
{"id": "PMID:184923", "title": "Mode of action of the bioreductive alkylating agent, 2,3-bis(chloromethyl)-1,4-naphthoquinone.", "content": "The bioreductive alkylating agent, 2,3-bis(chloromethyl)-1,4-napthoquinone (CMNQ), has been shown to inhibit the growth of Sarcoma 180 ascites cells in vivo. Evidence for the reductive activation of this agent via the mitochondrial respiratory chain was provided by CMNQ-induced oxidation of reduced nicotinamide adenine dinucleotide; the interaction was shown to be on the substrate side of the site of rotenone inhibition. Consistent with the concept that reduction of CMNQ to a hydroquinone results in the generation of an alkylating species (i.e., a quinone methide) was the finding that radioactivity from [14C]CMNQ present in Sarcoma 180 ascites cells was associated with DNA, RNA, and protein for a period of up to 72 hr after exposure to tumor-bearing animals to this agent. Inhibition of the incorporation of [3H]thymidine, [3H]uridine, and [14C]leucine into DNA, RNA, and protein, respectively, of Sarcoma 180 ascites cells was produced by this agent, with DNA biosynthesis being the most susceptible. The inhibitory effect of CMNQ on the formation of DNA was, at least in part, the result of a prevention of the conversion of thymidine to its nucleotide forms. This action was due to (a) a drug-induced decrease in intracellular levels of adenosine 5'-triphosphate, presumably resulting from uncoupling of oxidative phosphorylation by CMNQ; and (b) a partial loss of thymidine kinase activity in Sarcoma 180 cells, which did not appear to be due to direct inhibition of the enzyme by the drug. Although the primary event produced by CMNQ at the mitochondrial level appeared to be release of respiratory control, other effects of mitochondrial metabolism occurred. These included inhibition of reduced nicotinamide adenine dinucleotide and succinoxidase activities, as previously demonstrated, and mitochondrial swelling, which suggested interaction of CMNQ with the inner mitochondrial membrane. These findings indicate a variety of biochemical lesions are associated with the antineoplastic activity of CMNQ and demonstrate a relationship between the effects of this drug on mitochondrial respiratory control and DNA biosynthesis.", "contents": "Mode of action of the bioreductive alkylating agent, 2,3-bis(chloromethyl)-1,4-naphthoquinone. The bioreductive alkylating agent, 2,3-bis(chloromethyl)-1,4-napthoquinone (CMNQ), has been shown to inhibit the growth of Sarcoma 180 ascites cells in vivo. Evidence for the reductive activation of this agent via the mitochondrial respiratory chain was provided by CMNQ-induced oxidation of reduced nicotinamide adenine dinucleotide; the interaction was shown to be on the substrate side of the site of rotenone inhibition. Consistent with the concept that reduction of CMNQ to a hydroquinone results in the generation of an alkylating species (i.e., a quinone methide) was the finding that radioactivity from [14C]CMNQ present in Sarcoma 180 ascites cells was associated with DNA, RNA, and protein for a period of up to 72 hr after exposure to tumor-bearing animals to this agent. Inhibition of the incorporation of [3H]thymidine, [3H]uridine, and [14C]leucine into DNA, RNA, and protein, respectively, of Sarcoma 180 ascites cells was produced by this agent, with DNA biosynthesis being the most susceptible. The inhibitory effect of CMNQ on the formation of DNA was, at least in part, the result of a prevention of the conversion of thymidine to its nucleotide forms. This action was due to (a) a drug-induced decrease in intracellular levels of adenosine 5'-triphosphate, presumably resulting from uncoupling of oxidative phosphorylation by CMNQ; and (b) a partial loss of thymidine kinase activity in Sarcoma 180 cells, which did not appear to be due to direct inhibition of the enzyme by the drug. Although the primary event produced by CMNQ at the mitochondrial level appeared to be release of respiratory control, other effects of mitochondrial metabolism occurred. These included inhibition of reduced nicotinamide adenine dinucleotide and succinoxidase activities, as previously demonstrated, and mitochondrial swelling, which suggested interaction of CMNQ with the inner mitochondrial membrane. These findings indicate a variety of biochemical lesions are associated with the antineoplastic activity of CMNQ and demonstrate a relationship between the effects of this drug on mitochondrial respiratory control and DNA biosynthesis."}
{"id": "PMID:184924", "title": "The mechanism of 5-fluorouridine toxicity in Novikoff hepatoma cells.", "content": "The mechanism of 5-fluorouridine (FUrd) cytotoxicity in Novikoff hepatoma cells appears to vary under different experimental conditions. Continuous exposure to 1 X 10(-7) M FUrd results in a simple thymineless death that can be prevented by the addition of 1 X 10(-4) M thymidine to the culture medium. In contrast, 1 X 10(-4) M thymidine does not prevent the growth inhibition caused by a 1-hr exposure to 1 X 10(-5) M FUrd, despite the fact that it does prevent the inhibition of DNA synthesis. Although it has no effect on the inhibition of DNA synthesis, 1 X 10(-4) M uridine prevents the growth inhibition caused by a 1-hr exposure to 1 X 10(-5) M FUrd. Since 1 X 10(-4) M uridine, but not 1 X 10(-4) M thymidine, prevents the inhibition of ribosomal RNA maturation caused by a 1-hr exposure to 1 X 10(-5) M FUrd, it seems likely that the effects of the analog on RNA metabolism contribute significantly to the cytotoxic activity of the analog in this specific experimental situation.", "contents": "The mechanism of 5-fluorouridine toxicity in Novikoff hepatoma cells. The mechanism of 5-fluorouridine (FUrd) cytotoxicity in Novikoff hepatoma cells appears to vary under different experimental conditions. Continuous exposure to 1 X 10(-7) M FUrd results in a simple thymineless death that can be prevented by the addition of 1 X 10(-4) M thymidine to the culture medium. In contrast, 1 X 10(-4) M thymidine does not prevent the growth inhibition caused by a 1-hr exposure to 1 X 10(-5) M FUrd, despite the fact that it does prevent the inhibition of DNA synthesis. Although it has no effect on the inhibition of DNA synthesis, 1 X 10(-4) M uridine prevents the growth inhibition caused by a 1-hr exposure to 1 X 10(-5) M FUrd. Since 1 X 10(-4) M uridine, but not 1 X 10(-4) M thymidine, prevents the inhibition of ribosomal RNA maturation caused by a 1-hr exposure to 1 X 10(-5) M FUrd, it seems likely that the effects of the analog on RNA metabolism contribute significantly to the cytotoxic activity of the analog in this specific experimental situation."}
{"id": "PMID:184925", "title": "Cellular hypersensitivity of gp55 of RIII-murine mammary tumor virus and gp55-like protein of human breast cancers.", "content": "Previous studies suggested that immunogenic breast cancer tissues contained a component(s) that is antigenically similar to some component of murine mammary tumor virus (MuMTV) and resembles the glycoprotein, M.W. 55,000 (gp55), of RIII-MuMTV in molecular weight and charge density. This investigation measured in vitro cellular hypersensitivity responses of breast cancer patients to RIII mouse milk, purified RIII-gp55, C3H-MuMTV, autologous and homologous breast cancer tissues, gp50 of A-MuMTV, and preparations of Rauscher leukemia virus and Mason-Pfizer monkey virus. Particular attention was paid to cross-reactivity between gp55 and the other targets. The data indicate that responsiveness to C3H-MuMTV and RIII milk are linearly correlated with responsiveness to gp55. A preferential relationship was demonstrable between responses to gp55 and to those breast cancer tissues containing a gp55-like protein component (S-p50). The critical role of a gp55-like protein as the antigen responded to by breast cancer patients' in leukocytes was also suggested by the ability of anti-gp55 antiserum to decrease leukocyte responsiveness to RIII-gp55, C3H-MuMTV, and breast cancer tissues. In vitro cellular hypersensitivity against RIII-gp55 was preferentially found in prognostically favorable cases with immunogenic lesions. Further studies are needed to test the possibility that gp55 might be of value in the immunodiagnosis of early breast cancer, the monitoring of prognostically significant cellular hypersensitivity, and the induction of such hypersensitivity (immunoprophylaxis).", "contents": "Cellular hypersensitivity of gp55 of RIII-murine mammary tumor virus and gp55-like protein of human breast cancers. Previous studies suggested that immunogenic breast cancer tissues contained a component(s) that is antigenically similar to some component of murine mammary tumor virus (MuMTV) and resembles the glycoprotein, M.W. 55,000 (gp55), of RIII-MuMTV in molecular weight and charge density. This investigation measured in vitro cellular hypersensitivity responses of breast cancer patients to RIII mouse milk, purified RIII-gp55, C3H-MuMTV, autologous and homologous breast cancer tissues, gp50 of A-MuMTV, and preparations of Rauscher leukemia virus and Mason-Pfizer monkey virus. Particular attention was paid to cross-reactivity between gp55 and the other targets. The data indicate that responsiveness to C3H-MuMTV and RIII milk are linearly correlated with responsiveness to gp55. A preferential relationship was demonstrable between responses to gp55 and to those breast cancer tissues containing a gp55-like protein component (S-p50). The critical role of a gp55-like protein as the antigen responded to by breast cancer patients' in leukocytes was also suggested by the ability of anti-gp55 antiserum to decrease leukocyte responsiveness to RIII-gp55, C3H-MuMTV, and breast cancer tissues. In vitro cellular hypersensitivity against RIII-gp55 was preferentially found in prognostically favorable cases with immunogenic lesions. Further studies are needed to test the possibility that gp55 might be of value in the immunodiagnosis of early breast cancer, the monitoring of prognostically significant cellular hypersensitivity, and the induction of such hypersensitivity (immunoprophylaxis)."}
{"id": "PMID:184926", "title": "The metabolism-dependent maintenance of cell volume and ultrastructure in slices of Morris hepatoma 3924A.", "content": "The changes in water and electrolyte content of slices of Morris hepatoma 3924A induced by various conditions of incubation have been compared with the ultrastructural appearance of the tissue. Incubation at 1 degrees led to an increase of water, Na+, and Cl- content and to a loss of K+. There was simultaneous increase in size of the cells and intercellular spaces, loss of junctional complexes, increase in the number of microvilli, and fragmentation and dilation of the cytocavitary network. Subsequent incubation at 38 degrees in oxygenated medium led to a substantial reversal of all of these changes of composition and structure, which was well advanced within 10 min and largely complete by 60 min. The presence of 20 mM glucose in the medium somewhat enhanced the degree of recovery. A reduction of cell volume and intercellular spaces was evident both from the electron microscopic observations and measurements of the volume of inulin distribution. The presence of ouabain inhibited the net accumulation of K+ and much of the Na+ extrusion, but permitted about 50% of the net extrusion of water (accompanied by Na+ and Cl-) and had little effect on the ultrastructural recovery. The presence of glucose increased the resistance of volume and structural recovery of ouabain without releasing the inhibition of K+ accumulation. A marked feature of the recovering tissues was the Golgi apparatus, which assumed an appearance suggestive of increased activity when water extrusion was active. In slices using only endogenous substrate, cyanide and (to a lesser extent) oligomycin greatly inhibited the recovery of volume and structure. The presence of glucose permitted some recovery in the presence of cyanide. The control of cell volume in hepatoma 3924A appears to involve two separate components of water transport, one of which is sensitive, and one insensitive to ouabain. The ouabain-insensitive component appears to be especially related to the recovery of cell ultrastructure after incubation at 1 degrees, to be more sensitive to paucity of adenosine 5'-triphosphate, and to proceed by secretion of water, Na+, and Cl- into vesicles that fuse with the Golgi apparatus. This mechanism may be related to that for bile secretion in normal liver. The ouabain-sensitive component of water transport is a function of the mechanism for the coupled transport of Na+ and K+.", "contents": "The metabolism-dependent maintenance of cell volume and ultrastructure in slices of Morris hepatoma 3924A. The changes in water and electrolyte content of slices of Morris hepatoma 3924A induced by various conditions of incubation have been compared with the ultrastructural appearance of the tissue. Incubation at 1 degrees led to an increase of water, Na+, and Cl- content and to a loss of K+. There was simultaneous increase in size of the cells and intercellular spaces, loss of junctional complexes, increase in the number of microvilli, and fragmentation and dilation of the cytocavitary network. Subsequent incubation at 38 degrees in oxygenated medium led to a substantial reversal of all of these changes of composition and structure, which was well advanced within 10 min and largely complete by 60 min. The presence of 20 mM glucose in the medium somewhat enhanced the degree of recovery. A reduction of cell volume and intercellular spaces was evident both from the electron microscopic observations and measurements of the volume of inulin distribution. The presence of ouabain inhibited the net accumulation of K+ and much of the Na+ extrusion, but permitted about 50% of the net extrusion of water (accompanied by Na+ and Cl-) and had little effect on the ultrastructural recovery. The presence of glucose increased the resistance of volume and structural recovery of ouabain without releasing the inhibition of K+ accumulation. A marked feature of the recovering tissues was the Golgi apparatus, which assumed an appearance suggestive of increased activity when water extrusion was active. In slices using only endogenous substrate, cyanide and (to a lesser extent) oligomycin greatly inhibited the recovery of volume and structure. The presence of glucose permitted some recovery in the presence of cyanide. The control of cell volume in hepatoma 3924A appears to involve two separate components of water transport, one of which is sensitive, and one insensitive to ouabain. The ouabain-insensitive component appears to be especially related to the recovery of cell ultrastructure after incubation at 1 degrees, to be more sensitive to paucity of adenosine 5'-triphosphate, and to proceed by secretion of water, Na+, and Cl- into vesicles that fuse with the Golgi apparatus. This mechanism may be related to that for bile secretion in normal liver. The ouabain-sensitive component of water transport is a function of the mechanism for the coupled transport of Na+ and K+."}
{"id": "PMID:184927", "title": "Interaction of Na+ and K+ transport with aerobic energy metabolism in slices of Morris hepatoma 3924A.", "content": "Addition of increasing concentrations of glucose to slices of Morris hepatoma 3924A greatly stimulated aerobic lactate production and reduced respiration by 20%. Neither the adenine nucleotide content of the slices nor the calculated rate of adenosine 5'-triphosphate synthesis was altered. Ouabain reduced the rate of O2 uptake (by 20 to 25%) and of aerobic lactate production (by 25 to 50%) without affecting adenine nucleotide contents. The reduction by ouabain of the calculated rate of adenosine 5'-triphosphate synthesis was similar whether the slices were utilizing only endogenous substrate or exogenous glucose also. Raising the medium K+ concentration (and correspondingly reducing Na+) partially overcame the inhibition of ion transport by ouabain and partially restored the rates of respiration and aerobic lactate production toward control levels. Electron microscopic observations of mitochondria within the slices incubated under different conditions showed variations in configuration between \"orthodox,\" \"condensed\" and degenerating forms. Slices preincubated at 1 degrees showed mitochondria in the condensed form: they were restored to the orthodox configuration during incubation at 38 degrees in oxygenated medium. Oligomycin and glucose enhanced the transition, but ouabain reduced the number of mitochondria undergoing the change. The results suggest that in hepatoma 3924A utilization of adenosine 5'-triphosphate by ion transport exerts a simultaneous control of both respiration and aerobic glycolysis, which is presumably mediated by alterations in the availability of adenosine 5-diphosphate. The mitochondria undergo conformational transitions under conditions likely to affect local availability of adenosine 5'-diphosphate within cell compartments, but the transitions are not all externally added adenosine diphosphate on isolated mitochondria.", "contents": "Interaction of Na+ and K+ transport with aerobic energy metabolism in slices of Morris hepatoma 3924A. Addition of increasing concentrations of glucose to slices of Morris hepatoma 3924A greatly stimulated aerobic lactate production and reduced respiration by 20%. Neither the adenine nucleotide content of the slices nor the calculated rate of adenosine 5'-triphosphate synthesis was altered. Ouabain reduced the rate of O2 uptake (by 20 to 25%) and of aerobic lactate production (by 25 to 50%) without affecting adenine nucleotide contents. The reduction by ouabain of the calculated rate of adenosine 5'-triphosphate synthesis was similar whether the slices were utilizing only endogenous substrate or exogenous glucose also. Raising the medium K+ concentration (and correspondingly reducing Na+) partially overcame the inhibition of ion transport by ouabain and partially restored the rates of respiration and aerobic lactate production toward control levels. Electron microscopic observations of mitochondria within the slices incubated under different conditions showed variations in configuration between \"orthodox,\" \"condensed\" and degenerating forms. Slices preincubated at 1 degrees showed mitochondria in the condensed form: they were restored to the orthodox configuration during incubation at 38 degrees in oxygenated medium. Oligomycin and glucose enhanced the transition, but ouabain reduced the number of mitochondria undergoing the change. The results suggest that in hepatoma 3924A utilization of adenosine 5'-triphosphate by ion transport exerts a simultaneous control of both respiration and aerobic glycolysis, which is presumably mediated by alterations in the availability of adenosine 5-diphosphate. The mitochondria undergo conformational transitions under conditions likely to affect local availability of adenosine 5'-diphosphate within cell compartments, but the transitions are not all externally added adenosine diphosphate on isolated mitochondria."}
{"id": "PMID:184930", "title": "In vitro differentiation of teratomas and the distribution of creatine phosphokinase and plasminogen activator in teratocarcinoma-derived cells.", "content": "Mouse teratocarcinoma cells from embryoid bodies were cultured in vitro to permit their differentiation into a number of cell types. Two enzyme activities, creatine phosphokinase (CPK) and the protease plasminogen activator, were studied to follow the developmental sequence of events in these embryoid body-derived cell cultures. CPK activity increased with time in culture, indicating the appearance of new cell types with brain- or muscle-specific enzyme activities. Plasminogen activator was detectable in extracts of embryoid bodies. This protease activity first increased and then decreased to a low level as the embryoid bodies in culture developed into differentiated cell types. These cell cultures also showed a decreased potential for tumor formation in syngeneic mice as a function of time in culture. This decrease in tumorigenic potential was correlated with the appearance of differentiated cells in vitro. Simian virus 40 (SV40) was used to infect and transform cells derived from embryoid bodies in culture. This was done to permit the establishment of cloned teratocarcinoma-derived cell lines. Twenty-nine distinct cloned permanent cell lines (called SVTER) containing the SV40-specific tumor antigen were obtained. None of these cell lines was capable of producing tumors in syngeneic mice. An analysis of the levels of creatine phosphokinase and plasminogen activator in these SVTER cell lines indicated that : (a) some cell lines had high CPK activity and little or no plasminogen activator activity, (b) some cell lines contained high levels of plasminogen activator activity with little or no CPK activity, and (c) some cell lines contained neither of these enzyme activities. No example of a cell line with high levels of both enzyme activities was observed, indicating that these two enzymes may participate in mutually exclusive developmental pathways. The SVTER cell lines may therefore be useful in reconstructing these developmental pathways in vitro.", "contents": "In vitro differentiation of teratomas and the distribution of creatine phosphokinase and plasminogen activator in teratocarcinoma-derived cells. Mouse teratocarcinoma cells from embryoid bodies were cultured in vitro to permit their differentiation into a number of cell types. Two enzyme activities, creatine phosphokinase (CPK) and the protease plasminogen activator, were studied to follow the developmental sequence of events in these embryoid body-derived cell cultures. CPK activity increased with time in culture, indicating the appearance of new cell types with brain- or muscle-specific enzyme activities. Plasminogen activator was detectable in extracts of embryoid bodies. This protease activity first increased and then decreased to a low level as the embryoid bodies in culture developed into differentiated cell types. These cell cultures also showed a decreased potential for tumor formation in syngeneic mice as a function of time in culture. This decrease in tumorigenic potential was correlated with the appearance of differentiated cells in vitro. Simian virus 40 (SV40) was used to infect and transform cells derived from embryoid bodies in culture. This was done to permit the establishment of cloned teratocarcinoma-derived cell lines. Twenty-nine distinct cloned permanent cell lines (called SVTER) containing the SV40-specific tumor antigen were obtained. None of these cell lines was capable of producing tumors in syngeneic mice. An analysis of the levels of creatine phosphokinase and plasminogen activator in these SVTER cell lines indicated that : (a) some cell lines had high CPK activity and little or no plasminogen activator activity, (b) some cell lines contained high levels of plasminogen activator activity with little or no CPK activity, and (c) some cell lines contained neither of these enzyme activities. No example of a cell line with high levels of both enzyme activities was observed, indicating that these two enzymes may participate in mutually exclusive developmental pathways. The SVTER cell lines may therefore be useful in reconstructing these developmental pathways in vitro."}
{"id": "PMID:184932", "title": "Genes responsible for transformation by avian RNA tumor viruses.", "content": "Avian sarcoma viruses probably contain 4 genes. One of these, src, controls the process of transformation of the infected cell and has been located near the 3' end of the viral genome. The remaining 3 genes direct the synthesis of virion proteins: env (envelope proteins), pol (polymerase), and gag (internal proteins). They are probably in the order gag-poly-env-src. A scheme for the replication of these viruses is proposed, and several possible mechanisms for their origin and variability are discussed.", "contents": "Genes responsible for transformation by avian RNA tumor viruses. Avian sarcoma viruses probably contain 4 genes. One of these, src, controls the process of transformation of the infected cell and has been located near the 3' end of the viral genome. The remaining 3 genes direct the synthesis of virion proteins: env (envelope proteins), pol (polymerase), and gag (internal proteins). They are probably in the order gag-poly-env-src. A scheme for the replication of these viruses is proposed, and several possible mechanisms for their origin and variability are discussed."}
{"id": "PMID:184935", "title": "Homochromatographic and immunological analysis of controls of nucleolar gene function.", "content": "To compare regulation of nucleolar function of tumors and other tissues, it was necessary to develop assays of the fidelity of ribosomal DNA readouts. For this purpose, homochromatography analyses of complete T1 ribonuclease digestion products of the in vivo labeled 45 S preribosomal RNA were compared with those of 18S and of 28 S ribosomal RNA. Homochromatography analysis of the in vitro readout product of isolated nucleoli showed the presence of many large marker nucleotides of the in vivo 45 S preribosomal RNA. Moreover, no other large oligonucleotides were detected. The in vitro readout product of nucleolar chromatin had the same T1 ribonuclease digestion products, including the large marker of oligonucleotides. However, the in vitro readout product of nucleolar DNA contained no large marker T1 ribonuclease oligonucleotides. These results indicate that the fidelity of nucleolar readouts is controlled by regulatory proteins of the nucleolar chromatin. Differences were found in nucleolar proteins of normal rat liver and Novikoff hepatoma by immunological analyses. The possibility exists that differences in readout rates of tumor and other nucleoli are related to the protein difference detected by these immunological studies.", "contents": "Homochromatographic and immunological analysis of controls of nucleolar gene function. To compare regulation of nucleolar function of tumors and other tissues, it was necessary to develop assays of the fidelity of ribosomal DNA readouts. For this purpose, homochromatography analyses of complete T1 ribonuclease digestion products of the in vivo labeled 45 S preribosomal RNA were compared with those of 18S and of 28 S ribosomal RNA. Homochromatography analysis of the in vitro readout product of isolated nucleoli showed the presence of many large marker nucleotides of the in vivo 45 S preribosomal RNA. Moreover, no other large oligonucleotides were detected. The in vitro readout product of nucleolar chromatin had the same T1 ribonuclease digestion products, including the large marker of oligonucleotides. However, the in vitro readout product of nucleolar DNA contained no large marker T1 ribonuclease oligonucleotides. These results indicate that the fidelity of nucleolar readouts is controlled by regulatory proteins of the nucleolar chromatin. Differences were found in nucleolar proteins of normal rat liver and Novikoff hepatoma by immunological analyses. The possibility exists that differences in readout rates of tumor and other nucleoli are related to the protein difference detected by these immunological studies."}
{"id": "PMID:184936", "title": "Fatty acid oxidation, substrate shuttles, and activity of the citric acid cycle in hepatocellular carcinomas of varying differentiation.", "content": "Fatty acid oxidation, reconstituted substrate shuttles, and the activity of the citric acid cycle were studied in mitochondria isolated from Becker transplantable hepatocellular carcinoma H-252 AND Host livers, and the results were compared with those obtained with Morris hepatomas 7288CTC and 5123C. Whereas the activities of the malate-aspartate and the alpha-glycerophosphate shuttles were only slightly lower than those of host livers, the activity of the fatty acid shuttle was much lower in H-252 mitochondria. Oxygen uptake and CO2 production associated with the oxidation of fatty acids was much lower in tumors H-252 and 7288CTC, compared with host livers, whereas tumor 5123C mitochondria show a high capacity to oxidize fatty acids. Ketogenesis and beta-hydroxybutyrate dehydrogenase activity were also lower in tumor H-252 mitochondria. However, neither oxygen uptake associated with the oxidation of other respiratory substrates nor CO2 production from succinate or malate was strikingly elevated in these tumors. These factors suggest that the respiratory phosphorylation chain and activity of the citric acid cycle are fully functional in tumors H-252 and 7288CTC. The defects responsbile for the lower rates of fatty acid oxidation in these tumors probably involves the beta-oxidation pathway, as well as the activation of fatty acids. The impairment of fatty acid oxidation may explain the lower activity of the reconstituted fatty acid shuttle for transporting reducing equivalents into H-252 mitochondria. The different properties with regard to fatty acid oxidation in Morris hepatoma 5123C, compared with those in Becker H-252- AND Morris hepatoma 7288CTC, may reflect the different extent of differentiation in these tumors, the former being a slow-growing, well-differentiated tumor, whereas the latter represent tumors that are less differentiated and of more rapid growth rate.", "contents": "Fatty acid oxidation, substrate shuttles, and activity of the citric acid cycle in hepatocellular carcinomas of varying differentiation. Fatty acid oxidation, reconstituted substrate shuttles, and the activity of the citric acid cycle were studied in mitochondria isolated from Becker transplantable hepatocellular carcinoma H-252 AND Host livers, and the results were compared with those obtained with Morris hepatomas 7288CTC and 5123C. Whereas the activities of the malate-aspartate and the alpha-glycerophosphate shuttles were only slightly lower than those of host livers, the activity of the fatty acid shuttle was much lower in H-252 mitochondria. Oxygen uptake and CO2 production associated with the oxidation of fatty acids was much lower in tumors H-252 and 7288CTC, compared with host livers, whereas tumor 5123C mitochondria show a high capacity to oxidize fatty acids. Ketogenesis and beta-hydroxybutyrate dehydrogenase activity were also lower in tumor H-252 mitochondria. However, neither oxygen uptake associated with the oxidation of other respiratory substrates nor CO2 production from succinate or malate was strikingly elevated in these tumors. These factors suggest that the respiratory phosphorylation chain and activity of the citric acid cycle are fully functional in tumors H-252 and 7288CTC. The defects responsbile for the lower rates of fatty acid oxidation in these tumors probably involves the beta-oxidation pathway, as well as the activation of fatty acids. The impairment of fatty acid oxidation may explain the lower activity of the reconstituted fatty acid shuttle for transporting reducing equivalents into H-252 mitochondria. The different properties with regard to fatty acid oxidation in Morris hepatoma 5123C, compared with those in Becker H-252- AND Morris hepatoma 7288CTC, may reflect the different extent of differentiation in these tumors, the former being a slow-growing, well-differentiated tumor, whereas the latter represent tumors that are less differentiated and of more rapid growth rate."}
{"id": "PMID:184937", "title": "The limiting effect of transfer RNA's on the rate of protein synthesis in cell extracts of rapidly growing tumors.", "content": "Using crude cell extracts from rapidly growing animal and human tumors, we found that (a) the addition of homologous transfer RNA (tRNA) to these extracts stimulated polypeptide synthesis two-to threefold, while addition of heterologous tRNA did not have a similar effect; (b) addition of homologous as well as heterologous ribosomal RNA was also stimulatory; and (c) both stimulatory effects were additive. The possibility that the effect of homologous tRNA could be mediated by contaminating material (such as the \"translational control\" RNA) seems to be rulted out by experiments with highly purified tRNA preparations, which did not contain even traces of 18 S, 7 S, 5 S, and smaller than 4S RNA's. Control experiments showed that no loss of tRNA occurred either during preparation of the cell extracts or under the conditions of in vitro protein synthesis. The results obtained suggest possible occurrence of a deficiency in specific isoaccepting tRNA's in rapidly growing solid tumors.", "contents": "The limiting effect of transfer RNA's on the rate of protein synthesis in cell extracts of rapidly growing tumors. Using crude cell extracts from rapidly growing animal and human tumors, we found that (a) the addition of homologous transfer RNA (tRNA) to these extracts stimulated polypeptide synthesis two-to threefold, while addition of heterologous tRNA did not have a similar effect; (b) addition of homologous as well as heterologous ribosomal RNA was also stimulatory; and (c) both stimulatory effects were additive. The possibility that the effect of homologous tRNA could be mediated by contaminating material (such as the \"translational control\" RNA) seems to be rulted out by experiments with highly purified tRNA preparations, which did not contain even traces of 18 S, 7 S, 5 S, and smaller than 4S RNA's. Control experiments showed that no loss of tRNA occurred either during preparation of the cell extracts or under the conditions of in vitro protein synthesis. The results obtained suggest possible occurrence of a deficiency in specific isoaccepting tRNA's in rapidly growing solid tumors."}
{"id": "PMID:184938", "title": "Influence of vaccination with A/PR 8/34 (HO-N1) influenza virus on the oncogenic activity of polyoma virus in newborn Wistar rats.", "content": "Vaccination with the A/PR 8/34 (HO N1) strain of influenza virus can decrease significantly the oncogenic activity of polyomavirus in newborn Wistar rats. This effect was regularly observed when animals were vaccinated with 24 hr after birth, whereas vaccinations performed on Days 3 and 10 failed to influence the oncogenic potential of polyoma virus. In 3 series of experiments, influenza virus vaccination resulted in sigificantly decreased tumor rates, and, in a 4th series, in reduced tumor growth only. Heat inactivation of influenza virus failed to abolish its influence on the oncogenicity of polyoma virus. In most of the experiments, the antibody response to influenza virus was enhanced by inoculation of animals with polyoma virus. In contrast, polyoma virus antibody titers were, in some experiments, decreased, and, in others, not influenced by vaccination with influenza virus.", "contents": "Influence of vaccination with A/PR 8/34 (HO-N1) influenza virus on the oncogenic activity of polyoma virus in newborn Wistar rats. Vaccination with the A/PR 8/34 (HO N1) strain of influenza virus can decrease significantly the oncogenic activity of polyomavirus in newborn Wistar rats. This effect was regularly observed when animals were vaccinated with 24 hr after birth, whereas vaccinations performed on Days 3 and 10 failed to influence the oncogenic potential of polyoma virus. In 3 series of experiments, influenza virus vaccination resulted in sigificantly decreased tumor rates, and, in a 4th series, in reduced tumor growth only. Heat inactivation of influenza virus failed to abolish its influence on the oncogenicity of polyoma virus. In most of the experiments, the antibody response to influenza virus was enhanced by inoculation of animals with polyoma virus. In contrast, polyoma virus antibody titers were, in some experiments, decreased, and, in others, not influenced by vaccination with influenza virus."}
{"id": "PMID:184939", "title": "Analysis of the transfer RNA population of mouse mammary glands infected with a latent mammary tumor virus.", "content": "Mammary gland transfer RNA's  (tRNA'S) of CEH mice infected with mammary tumor virus were analyzed in the preneoplastic state and compared to tRNAs of virus-free C3Hf mice and another uninfected strain, C57BL/6, which is completely resistant to cancer. This quantitative study was based on the ability of each tRNA to fix its corresponding amino acid. The amount of each of the 17 tRNA's tested was identical for the three mammary glands. In addition, tRNA populations during lactation correlated with the amino acids incorporated into the lactoproteins synthesized, which indicates adapation of the tRNA's to protein biosynthesis. Qualitative chromatographic studies on reverse phase capillary columns Type 5 of 10 aminoacyl-tRNA's did not reveal any difference in the isoacceptor elution profiles. This shows that no new isoaccepting tRNA is associated with the mammary tumor virus at that stage, and that no viral modification of a host tRNA has occurred.", "contents": "Analysis of the transfer RNA population of mouse mammary glands infected with a latent mammary tumor virus. Mammary gland transfer RNA's  (tRNA'S) of CEH mice infected with mammary tumor virus were analyzed in the preneoplastic state and compared to tRNAs of virus-free C3Hf mice and another uninfected strain, C57BL/6, which is completely resistant to cancer. This quantitative study was based on the ability of each tRNA to fix its corresponding amino acid. The amount of each of the 17 tRNA's tested was identical for the three mammary glands. In addition, tRNA populations during lactation correlated with the amino acids incorporated into the lactoproteins synthesized, which indicates adapation of the tRNA's to protein biosynthesis. Qualitative chromatographic studies on reverse phase capillary columns Type 5 of 10 aminoacyl-tRNA's did not reveal any difference in the isoacceptor elution profiles. This shows that no new isoaccepting tRNA is associated with the mammary tumor virus at that stage, and that no viral modification of a host tRNA has occurred."}
{"id": "PMID:184940", "title": "Biosynthesis of albumin via a precursor protein in Morris hepatoma 5123tc.", "content": "The mechanism of albumin biosynthesis was studied in Morris hepatoma 5123tc in vivo and in hepatoma cell suspensions obtained by solubilizing the intercellular matrix with collagenase and hyaluronidase. In the in vivo experiments, L-[-14C]leucine was injected i.v. into rats bearing hepatomas in the muscles of both hind legs. After 14 min, tumors were removed and homogenized. A protein fraction quantitatively precipitable with antialbumin was isolated from the homogenate by acetone fractionation and precipitation with antiserum against serum albumin. This protein fraction was not homogeneous. With the use of 3 consecutive chromatographies on diethylaminoethyl cellulose, a very highly radioactive albumin-like protein could be separated from a large amount of only slightly radioactive albumin. In hepatoma cell suspensions incubated with L-[1-14C]leucine followed by a chase with excess nonradioactive L-leucine, radioactivity was incorporated first into the albumin-like protein and transferred thereafter into albumin, suggesting that albumin was synthesized via the albuminlike protein as precursor. In vivo, 1.8% of newly synthesized hepatoma protein was albumin or its precursor, compared with 1.2% in cell suspensions.", "contents": "Biosynthesis of albumin via a precursor protein in Morris hepatoma 5123tc. The mechanism of albumin biosynthesis was studied in Morris hepatoma 5123tc in vivo and in hepatoma cell suspensions obtained by solubilizing the intercellular matrix with collagenase and hyaluronidase. In the in vivo experiments, L-[-14C]leucine was injected i.v. into rats bearing hepatomas in the muscles of both hind legs. After 14 min, tumors were removed and homogenized. A protein fraction quantitatively precipitable with antialbumin was isolated from the homogenate by acetone fractionation and precipitation with antiserum against serum albumin. This protein fraction was not homogeneous. With the use of 3 consecutive chromatographies on diethylaminoethyl cellulose, a very highly radioactive albumin-like protein could be separated from a large amount of only slightly radioactive albumin. In hepatoma cell suspensions incubated with L-[1-14C]leucine followed by a chase with excess nonradioactive L-leucine, radioactivity was incorporated first into the albumin-like protein and transferred thereafter into albumin, suggesting that albumin was synthesized via the albuminlike protein as precursor. In vivo, 1.8% of newly synthesized hepatoma protein was albumin or its precursor, compared with 1.2% in cell suspensions."}
{"id": "PMID:184941", "title": "Prognostically significant protein components of human breast cancer tissues.", "content": "Cryostat sections of clinicopathologically characterized breast cancer tissues were eluted with phosphate-buffered 0.9% sodium chloride solution, pH 7.2. The proteins were then characterized by polyacrylamide gel electrophoresis with  and without prior treatment with sodium dodecyl sulfate. Approximately 65% of the brease cancer tissue eluates contained a prominent protein fraction with a molecular weight of 47,000 to 55,000 (p50). No such component was found in 15 of 17 eluates of benign breast tissue. Charge density studies disclosed that the p50 component included three populations of proteins that could be characterized according to the migration relative to gp55 derived from  RIII murine mammary tumor virus, namely, fast (F-p50), intermediate (I-p50), and slow (S-p50). Prognostically favorable pathological characteristics, i.e., stage, nuclear grade, and lymphoreticuloendothelial responses, were proportionately most frequently found among S-p50 bbreast cancers and were least frequently found among F-p50 breast cancers. It appears that the S-p50 component acts in vivo as a prognostically significant immunogen. Further knowledge of the relationship between protein characteristics and clinicopathological features of human breast cancers would contribute to our understanding of mammary carcinogenesis and biological behavior.", "contents": "Prognostically significant protein components of human breast cancer tissues. Cryostat sections of clinicopathologically characterized breast cancer tissues were eluted with phosphate-buffered 0.9% sodium chloride solution, pH 7.2. The proteins were then characterized by polyacrylamide gel electrophoresis with  and without prior treatment with sodium dodecyl sulfate. Approximately 65% of the brease cancer tissue eluates contained a prominent protein fraction with a molecular weight of 47,000 to 55,000 (p50). No such component was found in 15 of 17 eluates of benign breast tissue. Charge density studies disclosed that the p50 component included three populations of proteins that could be characterized according to the migration relative to gp55 derived from  RIII murine mammary tumor virus, namely, fast (F-p50), intermediate (I-p50), and slow (S-p50). Prognostically favorable pathological characteristics, i.e., stage, nuclear grade, and lymphoreticuloendothelial responses, were proportionately most frequently found among S-p50 bbreast cancers and were least frequently found among F-p50 breast cancers. It appears that the S-p50 component acts in vivo as a prognostically significant immunogen. Further knowledge of the relationship between protein characteristics and clinicopathological features of human breast cancers would contribute to our understanding of mammary carcinogenesis and biological behavior."}
{"id": "PMID:184942", "title": "Loss or persistence of the differentiated state of simian virus 40-induced hamster tumor cells before and after serial passage in culture.", "content": "The transformed cells that arise from among the hamster epithelial and mesenchymal cells exposed to SV40 in vitro are, as a rule, fibroblastoid and pleomorphic rather than epithelioid. Moreover, the neoplasms that these transformed cells induce in the allogeneic host are spindle cell sarcomas and pleomorphic sarcomas rather than carcinomas. Since this phenomenon may result from cellular dedifferentiation in culture, to the extent that the anaplastic morphology and lack of specialized function can no longer suggest the cell or origin, we investigated the fate of the differentiated state of cells of three types of SV40-induced hamster tumors before and after serial passage in vitro. The tumors evaluated were three reticulum cell sarcomas, three osteogenic sarcomas, and two lymphosarcomas of B-cell origin. Our data demonstrate that reticulum cell sarcoma cells lose their morphological differentiation soon after the original tumors are dissociated into cell suspensions but preserve their phagocytic activity throughout their in vitro passage. Osteogenic sarcoma cells lose their differentiated phenotype and their capacity to form osteoid during but not before their serial passage in culture. Lymphosarcoma cells preserve their lymphoid morphology and their ability to produce immunoglobulin even after many in vitro passages. These results indicate that, in many types of SV40-induced tumors, neoplastic cell dedifferentiation, following serial passage in culture, is responsible to a great extent for the emergence of new cell phenotypes lacking in morphological and functional features characteristic of the cells originally transformed by SV40.", "contents": "Loss or persistence of the differentiated state of simian virus 40-induced hamster tumor cells before and after serial passage in culture. The transformed cells that arise from among the hamster epithelial and mesenchymal cells exposed to SV40 in vitro are, as a rule, fibroblastoid and pleomorphic rather than epithelioid. Moreover, the neoplasms that these transformed cells induce in the allogeneic host are spindle cell sarcomas and pleomorphic sarcomas rather than carcinomas. Since this phenomenon may result from cellular dedifferentiation in culture, to the extent that the anaplastic morphology and lack of specialized function can no longer suggest the cell or origin, we investigated the fate of the differentiated state of cells of three types of SV40-induced hamster tumors before and after serial passage in vitro. The tumors evaluated were three reticulum cell sarcomas, three osteogenic sarcomas, and two lymphosarcomas of B-cell origin. Our data demonstrate that reticulum cell sarcoma cells lose their morphological differentiation soon after the original tumors are dissociated into cell suspensions but preserve their phagocytic activity throughout their in vitro passage. Osteogenic sarcoma cells lose their differentiated phenotype and their capacity to form osteoid during but not before their serial passage in culture. Lymphosarcoma cells preserve their lymphoid morphology and their ability to produce immunoglobulin even after many in vitro passages. These results indicate that, in many types of SV40-induced tumors, neoplastic cell dedifferentiation, following serial passage in culture, is responsible to a great extent for the emergence of new cell phenotypes lacking in morphological and functional features characteristic of the cells originally transformed by SV40."}
{"id": "PMID:184943", "title": "A cyclic adenosine 3':5'-monophosphate-mediated effect of cholera toxin on high-molecular-weight glycoprotein species of malignant cells.", "content": "A comparison of the Pronase-sensitive glycosylated species detectable under permissive and nonpermissive conditions by normal rat kidney cells transformed by a temperature-sensitive derivative of Rous sarcoma virus reveals relative decreased labeling of high-molecular-weight glycosylated species under conditions that allow the expression of transformation, in medium supplemented either with 0.5% calf serum or with human alpha2-macroglobulin, 100 mug/ml. Exposure of the cultures to cholera toxin or dibutyryl cyclic adenosine 3':5'-monophosphate leads to a relative increase in the glycosylation of the high-molecular weight species in both wild-type transformed and temperature-sensitive cells exposed to conditions that allow the expression of transformation.", "contents": "A cyclic adenosine 3':5'-monophosphate-mediated effect of cholera toxin on high-molecular-weight glycoprotein species of malignant cells. A comparison of the Pronase-sensitive glycosylated species detectable under permissive and nonpermissive conditions by normal rat kidney cells transformed by a temperature-sensitive derivative of Rous sarcoma virus reveals relative decreased labeling of high-molecular-weight glycosylated species under conditions that allow the expression of transformation, in medium supplemented either with 0.5% calf serum or with human alpha2-macroglobulin, 100 mug/ml. Exposure of the cultures to cholera toxin or dibutyryl cyclic adenosine 3':5'-monophosphate leads to a relative increase in the glycosylation of the high-molecular weight species in both wild-type transformed and temperature-sensitive cells exposed to conditions that allow the expression of transformation."}
{"id": "PMID:184944", "title": "Detection of the major glycoproteins of Friend leukemia virus (gp71) and the murine mammary tumor virus (gp52) on the surface of mouse cells.", "content": "Specific rabbit antisera to the major glycoproteins of Friend leukemia virus (gp71) and the mouse mammary tumor virus (gp52) were utilized to study the surfaces of C3H-, DBA-, BALB/c-, and C57BL-transformed and normal cells by immunoelectron microscopy. Antiserum to gp71 showed reactivity with all of the mouse cells tested regardless of strain, virus production, or state of transformation. In cells producing murine leukemia virus, budding viruses and other areas of the cell surface were consistently labeled with gp71 antiserum. A gp52-like antigen was likewise detected on both cell surfaces and virions of C3H and DBA cells producing the mammary tumor virus. Budding virions with surface spikes but with crescent-shaped nucleoids in C3H/HeJ cells were labeled specifically with gp52 antiserum. The antigen localized with anti-gp52 serum was detected in low concentration on the surface of nonvirus-producing cultures of a C57BL/6 sarcoma induced by the Schmidt-Ruppin D strain of Rous avian sarcoma virus (SRD-2), a BALB/c bone marrow culture (JLS-V9), and a normal BALB/c fibroblast culture (BALB/cF). Other cell cultures transformed by either C-type virus or methylcholanthrene failed to demonstrate gp52 antigen. Both gp52- and gp71-like antigens were found to be expressed simultaneously in C3H/HeJ, C3H-MT, DBA-MT, SRD-2 (transformed) and BALB/cF, JLS-V9, and C3H-1 (normal) cultures. Expression of gp52 antigen in the absence of gp71 was not detected in any of the cultures examined. These findings demonstrate the ubiquitous expression of gp71 in a wide variety of normal and transformed mouse cells while gp52 tends to be expressed predominantly in cells from mice with high mammary tumor incidence (C3H) and DBA), but only to a minor extent in cells from low mammary tumor incidence strains (BALB/c and C57BL).", "contents": "Detection of the major glycoproteins of Friend leukemia virus (gp71) and the murine mammary tumor virus (gp52) on the surface of mouse cells. Specific rabbit antisera to the major glycoproteins of Friend leukemia virus (gp71) and the mouse mammary tumor virus (gp52) were utilized to study the surfaces of C3H-, DBA-, BALB/c-, and C57BL-transformed and normal cells by immunoelectron microscopy. Antiserum to gp71 showed reactivity with all of the mouse cells tested regardless of strain, virus production, or state of transformation. In cells producing murine leukemia virus, budding viruses and other areas of the cell surface were consistently labeled with gp71 antiserum. A gp52-like antigen was likewise detected on both cell surfaces and virions of C3H and DBA cells producing the mammary tumor virus. Budding virions with surface spikes but with crescent-shaped nucleoids in C3H/HeJ cells were labeled specifically with gp52 antiserum. The antigen localized with anti-gp52 serum was detected in low concentration on the surface of nonvirus-producing cultures of a C57BL/6 sarcoma induced by the Schmidt-Ruppin D strain of Rous avian sarcoma virus (SRD-2), a BALB/c bone marrow culture (JLS-V9), and a normal BALB/c fibroblast culture (BALB/cF). Other cell cultures transformed by either C-type virus or methylcholanthrene failed to demonstrate gp52 antigen. Both gp52- and gp71-like antigens were found to be expressed simultaneously in C3H/HeJ, C3H-MT, DBA-MT, SRD-2 (transformed) and BALB/cF, JLS-V9, and C3H-1 (normal) cultures. Expression of gp52 antigen in the absence of gp71 was not detected in any of the cultures examined. These findings demonstrate the ubiquitous expression of gp71 in a wide variety of normal and transformed mouse cells while gp52 tends to be expressed predominantly in cells from mice with high mammary tumor incidence (C3H) and DBA), but only to a minor extent in cells from low mammary tumor incidence strains (BALB/c and C57BL)."}
{"id": "PMID:184945", "title": "Protein phosphotransferase activities and cyclic nucleotide action in proliferating lymphocytes.", "content": "Cyclic nucleotide levels, protein phosphotransferase activities, and cyclic nucleotide-binding proteins have been determined and partially characterized in the mouse lymphosarcoma P1798. This system is used as a model to understand the function of these activities in a rapidly proliferating cell. Adenosine 3':5'-monophosphate (cAMP) concentrations are 5-fold higher in the lymphosarcoma cells than in thymocytes. In both the thymocytes and malignant tissue, cAMP concentrations are increased by physiological concentrations of epinephrine and prostaglandin. The guanosine 3':5'-monophosphate (cGMP) level in the lymphosarcoma is 0.1 pmole/10(6) cells and is not modified by acetylcholine, prostaglandin F2alpha, or concanavalin A. Four protein phosphotransferase activities have been identified in the lymphosarcoma. These are the cAMP-dependent protein kinase type I and II isozymes and a \"histone kinase\" and a \"phosvitin kinase\"; neither of the latter two is regulated by cyclic nucleotides. Characterization of these enzymes was based on fractionation by DE 52 chromatography, substrate specificity, interaction with the protein inhibitor of cAMP-dependent protein kinases, and sucrose gradient sedimentation rates. Both the cAMP-dependent protein phosphotransferase activity and the phosvitin phosphotransferase activity are 2-to 4-fold elevated in the lymphosarcoma cells in comparison to thymocytes. cAMP binding is associated with both the type I and II isozymes and with a fraction tentatively designated as the regulatory subunit of these enzymes. cGMP also binds to this later fraction and to the partially purified fraction containing the type IcAMP-dependent enzyme. The histone phosphotransferase activity of this fraction is also stimulated by cGMP, but studies of the number of binding sites and of absorption to cAMP and cGMP affinity resins indicated that this fraction contains more than one species of cyclic nucleotide-binding protein.", "contents": "Protein phosphotransferase activities and cyclic nucleotide action in proliferating lymphocytes. Cyclic nucleotide levels, protein phosphotransferase activities, and cyclic nucleotide-binding proteins have been determined and partially characterized in the mouse lymphosarcoma P1798. This system is used as a model to understand the function of these activities in a rapidly proliferating cell. Adenosine 3':5'-monophosphate (cAMP) concentrations are 5-fold higher in the lymphosarcoma cells than in thymocytes. In both the thymocytes and malignant tissue, cAMP concentrations are increased by physiological concentrations of epinephrine and prostaglandin. The guanosine 3':5'-monophosphate (cGMP) level in the lymphosarcoma is 0.1 pmole/10(6) cells and is not modified by acetylcholine, prostaglandin F2alpha, or concanavalin A. Four protein phosphotransferase activities have been identified in the lymphosarcoma. These are the cAMP-dependent protein kinase type I and II isozymes and a \"histone kinase\" and a \"phosvitin kinase\"; neither of the latter two is regulated by cyclic nucleotides. Characterization of these enzymes was based on fractionation by DE 52 chromatography, substrate specificity, interaction with the protein inhibitor of cAMP-dependent protein kinases, and sucrose gradient sedimentation rates. Both the cAMP-dependent protein phosphotransferase activity and the phosvitin phosphotransferase activity are 2-to 4-fold elevated in the lymphosarcoma cells in comparison to thymocytes. cAMP binding is associated with both the type I and II isozymes and with a fraction tentatively designated as the regulatory subunit of these enzymes. cGMP also binds to this later fraction and to the partially purified fraction containing the type IcAMP-dependent enzyme. The histone phosphotransferase activity of this fraction is also stimulated by cGMP, but studies of the number of binding sites and of absorption to cAMP and cGMP affinity resins indicated that this fraction contains more than one species of cyclic nucleotide-binding protein."}
{"id": "PMID:184946", "title": "Alteration of mitochondrial function and lipid composition in Morris 7777 hepatoma.", "content": "Mitonchondria isolated from the Morris hepatoma 7777 demonstrated a markedly different phospholipid composition from those of control mitochondria, both with respect to the amounts of the various types present and the fatty acid composition. The level of polyunsaturated fatty acids in the mitochondrial phospholipids was lowered, wheras there was an increase in the level of monounsaturated fatty acids. Moreover, the usual distribution of saturated fatty acids at position 1 and polyunsaturated fatty acids at position 2 does not exist in hepatoma phospholipids; a high percentage of monounsaturated fatty acids was found at both positions. The cardiolipin content was lower in hepatoma mitochondria (3.7%) than in livers of animals with hepatomas (5.2%). There was, however, some compensation in the amount of acidic phospholipids in these mitochondria due to an increase in phosphatidylserine (4.9% versus 1.3%). The force-area curves of the hepatoma phospholipids spread on a monomolecular film demonstrated a smaller area per  molecule than those from liver mitochondria. The zeta potential of liposomes of the hepatoma phospholipids (-45) was less than those of control mitochondria (-81), as determined by microelectrophoresis. The calcium-stimulated phospholipase A activity of the hepatoma mitochondria appeared to be more readily expressed than the same activity in liver organelles. The maximal activity was lower, however, than that noted in liver mitochondria. Furthermore, by following the incorporation of [3H]ethanolamine into mitochondria phospholipids, it was established that the conversion of glycerophosphorylethanolamine to glycerophosphorylcholine was increased in the hepatoma. These observations suggest dramatic changes in phospholipid metabolism in the hepatoma, at the level of both the endoplasmic reticulum and the mitochondrion. Accompanying the changes in phospholipid compositon and metabolism were alterations in mitochondrial energy-linked processes. The hepatoma mitochondria demonstrated lower respiratory control ratios even when isolated in an isotonic solution containing 1mM ethylenediaminetetraacetate and bovine serum albumin (0.5 mg/ml). This was due to increased state 4 respiration.", "contents": "Alteration of mitochondrial function and lipid composition in Morris 7777 hepatoma. Mitonchondria isolated from the Morris hepatoma 7777 demonstrated a markedly different phospholipid composition from those of control mitochondria, both with respect to the amounts of the various types present and the fatty acid composition. The level of polyunsaturated fatty acids in the mitochondrial phospholipids was lowered, wheras there was an increase in the level of monounsaturated fatty acids. Moreover, the usual distribution of saturated fatty acids at position 1 and polyunsaturated fatty acids at position 2 does not exist in hepatoma phospholipids; a high percentage of monounsaturated fatty acids was found at both positions. The cardiolipin content was lower in hepatoma mitochondria (3.7%) than in livers of animals with hepatomas (5.2%). There was, however, some compensation in the amount of acidic phospholipids in these mitochondria due to an increase in phosphatidylserine (4.9% versus 1.3%). The force-area curves of the hepatoma phospholipids spread on a monomolecular film demonstrated a smaller area per  molecule than those from liver mitochondria. The zeta potential of liposomes of the hepatoma phospholipids (-45) was less than those of control mitochondria (-81), as determined by microelectrophoresis. The calcium-stimulated phospholipase A activity of the hepatoma mitochondria appeared to be more readily expressed than the same activity in liver organelles. The maximal activity was lower, however, than that noted in liver mitochondria. Furthermore, by following the incorporation of [3H]ethanolamine into mitochondria phospholipids, it was established that the conversion of glycerophosphorylethanolamine to glycerophosphorylcholine was increased in the hepatoma. These observations suggest dramatic changes in phospholipid metabolism in the hepatoma, at the level of both the endoplasmic reticulum and the mitochondrion. Accompanying the changes in phospholipid compositon and metabolism were alterations in mitochondrial energy-linked processes. The hepatoma mitochondria demonstrated lower respiratory control ratios even when isolated in an isotonic solution containing 1mM ethylenediaminetetraacetate and bovine serum albumin (0.5 mg/ml). This was due to increased state 4 respiration."}
{"id": "PMID:184947", "title": "Susceptibility of xeroderma pigmentosum cells to transformation by murine and feline sarcoma viruses.", "content": "Among various strains of skin fibroblasts tested, two strains derived from xeroderma pigmentosum (XP) patients (ages 19 and 25) with neurological complications and two strains obtained from heterozygotes (ages 54 and 18) showed relatively higher susceptibility than normal age-matched controls to transformation by feline sarcoma virus (FSV). Only one strain from a normal individual also showed a high susceptibility. Generally, there was a parallelism in susceptibilities to FSV and Kirsten murine sarcoma virus (KiMsv). However, cells from normal individuals of 46 years or older exhibited high ratios of FSV:KiMSV titers which were due to their lower susceptibility to KiMSV. Cells from two XP patients (ages 25 and 22) and a heterozygote (age 18), who were in a younger age group, manifested such a differential susceptibility to FSV and KiMSV. There was a correlation between the relative sensitivity of XP cells to the cytotoxic effect of 4-nitroquinoline 1-oxide and killing effect of UV light. Pretreatment of fibroblasts from three XP patients by a subtoxic dose of 4-nitroquinoline 1-oxide 24 hr before viral infection facilitated transformation by KiMSV and FSV, whereas no such effect was observed with three normal cells strains similarly treated.", "contents": "Susceptibility of xeroderma pigmentosum cells to transformation by murine and feline sarcoma viruses. Among various strains of skin fibroblasts tested, two strains derived from xeroderma pigmentosum (XP) patients (ages 19 and 25) with neurological complications and two strains obtained from heterozygotes (ages 54 and 18) showed relatively higher susceptibility than normal age-matched controls to transformation by feline sarcoma virus (FSV). Only one strain from a normal individual also showed a high susceptibility. Generally, there was a parallelism in susceptibilities to FSV and Kirsten murine sarcoma virus (KiMsv). However, cells from normal individuals of 46 years or older exhibited high ratios of FSV:KiMSV titers which were due to their lower susceptibility to KiMSV. Cells from two XP patients (ages 25 and 22) and a heterozygote (age 18), who were in a younger age group, manifested such a differential susceptibility to FSV and KiMSV. There was a correlation between the relative sensitivity of XP cells to the cytotoxic effect of 4-nitroquinoline 1-oxide and killing effect of UV light. Pretreatment of fibroblasts from three XP patients by a subtoxic dose of 4-nitroquinoline 1-oxide 24 hr before viral infection facilitated transformation by KiMSV and FSV, whereas no such effect was observed with three normal cells strains similarly treated."}
{"id": "PMID:184948", "title": "Prolactin receptors and androgen-induced regression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma.", "content": "Prolactin reverses the inhibitory effects of pharmacological doses of androgen on 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth (Quadri, S.K., Kledzik, G.S., and Meites, J.J. Natl. Cancer Inst., 52: 875-878,1974). To determine whether this effect is due to an alteration in the ability of the tumor cell to bind prolactin, we have quantitated prolactin receptors in androgen-responsive and nonresponsive tumors. Prolactin receptors were measured with 125I-labeled ovine prolactin in a subcellular fraction which reproducibly contained 60 to 80% of the total receptor present in tumor homogenates. Prolactin binding was reversible, reached a steady state in 9 hr, and was completed by excess unlabeled prolactin. Prolactin bound to its receptor with a Kd of approximately 1 X 10(-10) M. Growing tumors were biopsied, and rats bearing regrown tumors were given injections of 4 mg testosterone propionate twice a week. Prolactin receptors were reduced in most of the tumors, which regressed after testosterone treatment by an average of 63% compared to the pretreatment biopsy specimens. Nonresponsive tumors and vehicle-injected controls showed no signifcant alterations in receptor content. This reduction of prolactin receptors is probably insufficient to account for androgen-induced mammary tumor regression.", "contents": "Prolactin receptors and androgen-induced regression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma. Prolactin reverses the inhibitory effects of pharmacological doses of androgen on 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth (Quadri, S.K., Kledzik, G.S., and Meites, J.J. Natl. Cancer Inst., 52: 875-878,1974). To determine whether this effect is due to an alteration in the ability of the tumor cell to bind prolactin, we have quantitated prolactin receptors in androgen-responsive and nonresponsive tumors. Prolactin receptors were measured with 125I-labeled ovine prolactin in a subcellular fraction which reproducibly contained 60 to 80% of the total receptor present in tumor homogenates. Prolactin binding was reversible, reached a steady state in 9 hr, and was completed by excess unlabeled prolactin. Prolactin bound to its receptor with a Kd of approximately 1 X 10(-10) M. Growing tumors were biopsied, and rats bearing regrown tumors were given injections of 4 mg testosterone propionate twice a week. Prolactin receptors were reduced in most of the tumors, which regressed after testosterone treatment by an average of 63% compared to the pretreatment biopsy specimens. Nonresponsive tumors and vehicle-injected controls showed no signifcant alterations in receptor content. This reduction of prolactin receptors is probably insufficient to account for androgen-induced mammary tumor regression."}
{"id": "PMID:184949", "title": "Antigenically active nonhistone chromatin proteins in cancer cells.", "content": "Two-dimensional polyacrylamide gel electrophoresis shows that in nuclei of Novikoff hepatoma ascites cells there are approximately 75 proteins in the chromatin fraction soluble in 3 M NaCl:7 M urea. Dialysis of this fraction to an ionic strength of 0.15 produces a soluble fraction and a precipitate. The proteins in the soluble fraction have been reported to be active in gene control. Antibodies to the soluble fraction distribute diffusely throughout the nucleus, and antibodies to the precipitate localized primarily in the nucleolus and the nuclear ribonucleoprotein network. The nucleolar proteins differ from the extranucleolar proteins in antigenicity and labeling patterns. The development of methods for isolation, purification, and identification of nuclear proteins provided the opportunity for analysis of chromatin antigens in tumor cells. Utilizing two-dimensional preparative polyacrylamide gel techniques as well as conventional procedures, several nuclear proteins have been isolated in electrophoretically homogeneous states including protein A-24, a histone-like nonhistone protein; C-14, a protein that stimulates nucleolar RNA polymerase; and a chromatin antigen soluble in 3 M NaCl:7 M urea that remains soluble after dialysis to 0.15 M NaCl to precipitate the histones and the DNA. This antigen has been found in the chromatin of both the Novikoff hepatoma and the Walker 256 carcinosarcoma but not in the chromatin of either normal or regenerating liver. It is a nonhistone nuclear protein as indicated by its amino acid analysis in which the ratio of the number of acidic to basic amino acids is approximately 1.4. Further studies are in progress on the function and structure of this chromatin protein. As an approach to analysis of relative  rates of synthesis of this antigen and otherproteins, the products of translation of messenger RNA of Novikoff hepatoma and normal liver are being analyzed by autoradiography of two-dimensional electrophoretic gels.", "contents": "Antigenically active nonhistone chromatin proteins in cancer cells. Two-dimensional polyacrylamide gel electrophoresis shows that in nuclei of Novikoff hepatoma ascites cells there are approximately 75 proteins in the chromatin fraction soluble in 3 M NaCl:7 M urea. Dialysis of this fraction to an ionic strength of 0.15 produces a soluble fraction and a precipitate. The proteins in the soluble fraction have been reported to be active in gene control. Antibodies to the soluble fraction distribute diffusely throughout the nucleus, and antibodies to the precipitate localized primarily in the nucleolus and the nuclear ribonucleoprotein network. The nucleolar proteins differ from the extranucleolar proteins in antigenicity and labeling patterns. The development of methods for isolation, purification, and identification of nuclear proteins provided the opportunity for analysis of chromatin antigens in tumor cells. Utilizing two-dimensional preparative polyacrylamide gel techniques as well as conventional procedures, several nuclear proteins have been isolated in electrophoretically homogeneous states including protein A-24, a histone-like nonhistone protein; C-14, a protein that stimulates nucleolar RNA polymerase; and a chromatin antigen soluble in 3 M NaCl:7 M urea that remains soluble after dialysis to 0.15 M NaCl to precipitate the histones and the DNA. This antigen has been found in the chromatin of both the Novikoff hepatoma and the Walker 256 carcinosarcoma but not in the chromatin of either normal or regenerating liver. It is a nonhistone nuclear protein as indicated by its amino acid analysis in which the ratio of the number of acidic to basic amino acids is approximately 1.4. Further studies are in progress on the function and structure of this chromatin protein. As an approach to analysis of relative  rates of synthesis of this antigen and otherproteins, the products of translation of messenger RNA of Novikoff hepatoma and normal liver are being analyzed by autoradiography of two-dimensional electrophoretic gels."}
{"id": "PMID:184950", "title": "The effect of exposure to dibutyryl cyclic adenylic acid on the membrane antigenicity of SV40 tumor cells.", "content": "When SV40 tumor cells (F5-1) in culture were treated with dibutyryl cyclic adenylic acid (DbcAMP),marked alterations occurred in their growth and morphology. Additionally, the incorporation or uptake of labeled thymidine, uridine, phenylalanine, and choline were reduced by this treatment. These modifications with DbcAMP exposure produced conditions simulating those of a contact-inhibited state. The immunization of hamsters with X-irradiated tumor cells previously cultured in the presence of DbcAMP indicated that the tumor-specific transplantation antigens and/or fetal antigens were altered during short-term expsoure to DbcAMP. Further examination of membrane antigens of SV40 tumor cells using the isotopic antiglobulin technique demonstrated a significant reduction in the tumor membrane antigen on cells cultured with DbcAMP.", "contents": "The effect of exposure to dibutyryl cyclic adenylic acid on the membrane antigenicity of SV40 tumor cells. When SV40 tumor cells (F5-1) in culture were treated with dibutyryl cyclic adenylic acid (DbcAMP),marked alterations occurred in their growth and morphology. Additionally, the incorporation or uptake of labeled thymidine, uridine, phenylalanine, and choline were reduced by this treatment. These modifications with DbcAMP exposure produced conditions simulating those of a contact-inhibited state. The immunization of hamsters with X-irradiated tumor cells previously cultured in the presence of DbcAMP indicated that the tumor-specific transplantation antigens and/or fetal antigens were altered during short-term expsoure to DbcAMP. Further examination of membrane antigens of SV40 tumor cells using the isotopic antiglobulin technique demonstrated a significant reduction in the tumor membrane antigen on cells cultured with DbcAMP."}
{"id": "PMID:184951", "title": "Biological and biochemical properties of soluble tumor-specific transplantation antigen of a simian virus 40-induced neoplasm.", "content": "We have solubilized by limited papain digestion and partially purified the tumor rejection antigen, tumor-specific transplantation antigens (TSTA), from membranes of a simian virus 40-induced sarcoma. Uniform-sized materials with a molecular weight range of 50,000 have retained their tumor rejection activities through the purification procedures. The simian virus 40 TSTA have been separated from H-2 activity by affinity chromatography on concanavalin A columns and no evidence was found for H-2 antigens in the unbound fraction (I) of concanavalin A containing TSTA activity. A reduced yield from the crude soluble fraction was observed with Fraction I of concanavalin A material and this may indeed represent fragmentation of antigen during papain digestion. These results stand in contrast to purification of histocompatibility antigens (H-2alpha) using the same methods and techniques. Low concentrations of simian virus 40 TSTA crude soluble materials were nervertheless biologically active. A concentration as low as 4 mug protein provided 50% tumor rejection and 0.1 mug protein provided lymphocyte stimulation. Both assays reflected specificity of response.", "contents": "Biological and biochemical properties of soluble tumor-specific transplantation antigen of a simian virus 40-induced neoplasm. We have solubilized by limited papain digestion and partially purified the tumor rejection antigen, tumor-specific transplantation antigens (TSTA), from membranes of a simian virus 40-induced sarcoma. Uniform-sized materials with a molecular weight range of 50,000 have retained their tumor rejection activities through the purification procedures. The simian virus 40 TSTA have been separated from H-2 activity by affinity chromatography on concanavalin A columns and no evidence was found for H-2 antigens in the unbound fraction (I) of concanavalin A containing TSTA activity. A reduced yield from the crude soluble fraction was observed with Fraction I of concanavalin A material and this may indeed represent fragmentation of antigen during papain digestion. These results stand in contrast to purification of histocompatibility antigens (H-2alpha) using the same methods and techniques. Low concentrations of simian virus 40 TSTA crude soluble materials were nervertheless biologically active. A concentration as low as 4 mug protein provided 50% tumor rejection and 0.1 mug protein provided lymphocyte stimulation. Both assays reflected specificity of response."}
{"id": "PMID:184953", "title": "Alterations in peripheral nerves of rats treated with chlorphentermine or with iprindole.", "content": "This study deals with the effects of two amphiphilic lipidosis-inducing drugs (chlorphentermine, iprindole) upon the ultrastructure of peripheral nerves of rats. After prolonged drug treatment the preterminal and terminal axoplasm of motor and sensory nerves within skeletal muscles contain numerous abnormal inclusions (osmiophilic conglomerates, autophagic vacuoles, lamellated bodies). By contrast, the axons within large peripheral nerves are little effected. The present observations are tentatively interpreted as resulting from interference with catabolic processes involved in the normal turnover of axoplasmic constituents at the nerve terminal. The exact pathogenesis and the functional significance of these alterations remain to be elucidated.", "contents": "Alterations in peripheral nerves of rats treated with chlorphentermine or with iprindole. This study deals with the effects of two amphiphilic lipidosis-inducing drugs (chlorphentermine, iprindole) upon the ultrastructure of peripheral nerves of rats. After prolonged drug treatment the preterminal and terminal axoplasm of motor and sensory nerves within skeletal muscles contain numerous abnormal inclusions (osmiophilic conglomerates, autophagic vacuoles, lamellated bodies). By contrast, the axons within large peripheral nerves are little effected. The present observations are tentatively interpreted as resulting from interference with catabolic processes involved in the normal turnover of axoplasmic constituents at the nerve terminal. The exact pathogenesis and the functional significance of these alterations remain to be elucidated."}
{"id": "PMID:184954", "title": "The ultrastructure of the accessory sex organs of the male rat. XI. Nuclear alterations of prostatic epithelial cells induced by castration.", "content": "The fine structure of the nuclei of epithelial cells of the dorsal lobe of the rat prostate were studied 2, 3, 5, 7 and 21 days after castration. The nucleolus appears to undergo a progressive disorganisation with partial fragmentation and dispersion of its normal components. Changes in the nucleoplasm were primarily reflected by a condensation of chromatin, particularly along the nuclear membrane and adjacent to the nucleolus. Later, different types of intranuclear inclusions were observed. After 21 days, the nuclei were characterized by an irregular outline with large indentation. Within the nucleoplasm aggregates of coarse granular chromatin were found. No cell necrosis was observed, indicating that androgen deprivation results in a remodeling of the cell to a less active state with marked cellular alterations and cessation of secretion, but apparently with some of their basic functions still intact. Injections of testosterone completely reverse the castrated-induced alterations. The changes observed are assumed to be due to the withdrawal of the androgenic stimulus, with a direct influence on the secretory function of the cell. The findings support the view that the stimulating secretory effect of androgen is mediated via an intranuclear androgen receptor, probably located in the nucleolus-associated-chromatin. It is also proposed that the secretory function of the epithelial cells of the prostatic complex, initiated by androgens, may be regulated by an intranuclear secretory center.", "contents": "The ultrastructure of the accessory sex organs of the male rat. XI. Nuclear alterations of prostatic epithelial cells induced by castration. The fine structure of the nuclei of epithelial cells of the dorsal lobe of the rat prostate were studied 2, 3, 5, 7 and 21 days after castration. The nucleolus appears to undergo a progressive disorganisation with partial fragmentation and dispersion of its normal components. Changes in the nucleoplasm were primarily reflected by a condensation of chromatin, particularly along the nuclear membrane and adjacent to the nucleolus. Later, different types of intranuclear inclusions were observed. After 21 days, the nuclei were characterized by an irregular outline with large indentation. Within the nucleoplasm aggregates of coarse granular chromatin were found. No cell necrosis was observed, indicating that androgen deprivation results in a remodeling of the cell to a less active state with marked cellular alterations and cessation of secretion, but apparently with some of their basic functions still intact. Injections of testosterone completely reverse the castrated-induced alterations. The changes observed are assumed to be due to the withdrawal of the androgenic stimulus, with a direct influence on the secretory function of the cell. The findings support the view that the stimulating secretory effect of androgen is mediated via an intranuclear androgen receptor, probably located in the nucleolus-associated-chromatin. It is also proposed that the secretory function of the epithelial cells of the prostatic complex, initiated by androgens, may be regulated by an intranuclear secretory center."}
{"id": "PMID:184955", "title": "Exocrine pancreas under experimental conditions. I. Formation of paracrystalline inclusions in vivo.", "content": "After the application of parachlorophenylalanine (pCPA), an amino acid analogue, paracrystalline inclusions are observed in the exocrine pancreas of the rat. The formation of the paracrystalline structures varies according to the dose and the time of examination. Although the first alterations can be seen in the Golgi apparatus and the condensing vacuoles, the main localization of these structures is within the cisternae of the RER. At the same time as degenerative changes occur in the cells, involving autophagic and heterophagic processes, regeneration also takes place. With the freeze-fracturing method, the paracrystalline inclusions are interpreted as lamellae or plates of probably altered secretory proteins in extremely extended RER-cisternae. The fracture surfaces of the paracrystals show a periodicity of about 80 A running diagnonally to the main axis of the paracrystalline structures, which are mainly oriented from the basal parts of the exocrine pancreatic cells to the cell apices. The mechanism of paracrystalline formation is discussed on the basis of the morphologic results. It could be shown that after pCPA administration the amylase content is decreased concomittantly with degranulation. pCPA seems not to be incorporated into secretory proteins; high intracellular concentrations, however, are required to induce the formation of the paracrystalline structures. This morphological study is the basis for other studies dealing with secretion and intracellular transport in the pancreatic acinar cell under experimental conditions.", "contents": "Exocrine pancreas under experimental conditions. I. Formation of paracrystalline inclusions in vivo. After the application of parachlorophenylalanine (pCPA), an amino acid analogue, paracrystalline inclusions are observed in the exocrine pancreas of the rat. The formation of the paracrystalline structures varies according to the dose and the time of examination. Although the first alterations can be seen in the Golgi apparatus and the condensing vacuoles, the main localization of these structures is within the cisternae of the RER. At the same time as degenerative changes occur in the cells, involving autophagic and heterophagic processes, regeneration also takes place. With the freeze-fracturing method, the paracrystalline inclusions are interpreted as lamellae or plates of probably altered secretory proteins in extremely extended RER-cisternae. The fracture surfaces of the paracrystals show a periodicity of about 80 A running diagnonally to the main axis of the paracrystalline structures, which are mainly oriented from the basal parts of the exocrine pancreatic cells to the cell apices. The mechanism of paracrystalline formation is discussed on the basis of the morphologic results. It could be shown that after pCPA administration the amylase content is decreased concomittantly with degranulation. pCPA seems not to be incorporated into secretory proteins; high intracellular concentrations, however, are required to induce the formation of the paracrystalline structures. This morphological study is the basis for other studies dealing with secretion and intracellular transport in the pancreatic acinar cell under experimental conditions."}
{"id": "PMID:184956", "title": "The general occurrence of intramitochondrial crystals in Hydra cells.", "content": "Intramitochondrial crystals are found in normal Hydra as well as in animals undergoing various conditions (budding, regenerating, eserine-treated, and sexual). They appear in all regions of the animal, but seem to be more prevalent at or near the extremities: hypostome, tentacles and basal disk. They are found in all of the seven basic cell types: interstitial, cnidocyte, nerve, epithelio-muscular, gland, mucous and digestive cells. The chemical nature of the intramitochondrial crystals is unknown and their significance remains speculative.", "contents": "The general occurrence of intramitochondrial crystals in Hydra cells. Intramitochondrial crystals are found in normal Hydra as well as in animals undergoing various conditions (budding, regenerating, eserine-treated, and sexual). They appear in all regions of the animal, but seem to be more prevalent at or near the extremities: hypostome, tentacles and basal disk. They are found in all of the seven basic cell types: interstitial, cnidocyte, nerve, epithelio-muscular, gland, mucous and digestive cells. The chemical nature of the intramitochondrial crystals is unknown and their significance remains speculative."}
{"id": "PMID:184957", "title": "Glucose uptake by normal human breast tissue in organ culture. Influence of insulin and other additives.", "content": "Normal human breast tissue explants were cultured in a synthetic basic medium with and without additives. The mean daily glucose uptake per explant was measured under six basic conditions. Our results show that glucose uptake is strongly related to the glucose concentration of the medium. On the other hand insulin does not affect significantly glucose uptake in vitro, but does enhance mitotic activity. These findings support a role for insulin in promoting D.N.A. synthesis rather than in controlling glucose metabolism of human mammary tissue in vitro.", "contents": "Glucose uptake by normal human breast tissue in organ culture. Influence of insulin and other additives. Normal human breast tissue explants were cultured in a synthetic basic medium with and without additives. The mean daily glucose uptake per explant was measured under six basic conditions. Our results show that glucose uptake is strongly related to the glucose concentration of the medium. On the other hand insulin does not affect significantly glucose uptake in vitro, but does enhance mitotic activity. These findings support a role for insulin in promoting D.N.A. synthesis rather than in controlling glucose metabolism of human mammary tissue in vitro."}
{"id": "PMID:184959", "title": "The initiation region of the SV40 VP1 gene.", "content": "The sequence of 15 nucleotides located at the 5' terminus of the plus strand of the SV40 Hind K fragment has been determined as (5') A-G-C-T-T-A-T-G-A-A-G-A-T-G-G (3'). The 3' on OH terminal G of this segment is part of the G-C-C codeword for the N terminal alanine of the VP1 protein. This region therefore presumably corresponds to a ribosome binding site on the 16S late mRNA. Complementarily to the 3' OH of eucaryotic 18S ribosomal RNA and homology with the BMV coat ribosome binding site are discussed.", "contents": "The initiation region of the SV40 VP1 gene. The sequence of 15 nucleotides located at the 5' terminus of the plus strand of the SV40 Hind K fragment has been determined as (5') A-G-C-T-T-A-T-G-A-A-G-A-T-G-G (3'). The 3' on OH terminal G of this segment is part of the G-C-C codeword for the N terminal alanine of the VP1 protein. This region therefore presumably corresponds to a ribosome binding site on the 16S late mRNA. Complementarily to the 3' OH of eucaryotic 18S ribosomal RNA and homology with the BMV coat ribosome binding site are discussed."}
{"id": "PMID:184960", "title": "Heterozygous familial hypercholesterolemia: failure of normal allele to compensate for mutant allele at a regulated genetic locus.", "content": "In normal human fibroblasts, the synthesis of a cell surface receptor for plasma low density lipoprotein (LDL) is regulated by a sensitive system of feedback suppression. The number of functional LDL receptors declines by more than 20 fold when cellular stores of esterified cholesterol are increased by incubation of cells with an exogenous source of cholesterol. Fibroblasts from patients with the heterozygous form of familial hypercholesterolemia (FH) possess one functional allele and one nonfunctional allele at the LDL receptor locus. In the current studies, we have examined the effect that this deficiency produces upon the pattern of regulation of the single functional allele at the LDL receptor locus. Under growth conditions that induced a maximal rate of LDL receptor synthesis (that is, growth in the absence of an exogenous source of cholesterol), the FH heterozygote cells produced about one half as many functional LDL receptors as did the normal cells. More importantly, when grown in the presence of increasing amounts of exogenous cholesterol, the FH heterozygote and normal cells suppressed their respective LDL receptor activities in parallel. Over a wide range of LDL receptor activities, at each level of cellular esterified cholesterol, the FH heterozygote cells expressed about one half as many receptors as did the normal cells. These data indicate that in the FH heterozygote cells, the receptor regulatory mechanism dictates that the normal allele produce only the amount of gene product that it would normally produce at a given level of cellular esterified cholesterol. The failure of the regulatory mechanism to stimulate the normal allele at the LDL receptor locus to produce twice its normal amount of gene product leaves the FH heterozygote cells with a persistent 50% deficiency in LDL receptors under all conditions of cell growth.", "contents": "Heterozygous familial hypercholesterolemia: failure of normal allele to compensate for mutant allele at a regulated genetic locus. In normal human fibroblasts, the synthesis of a cell surface receptor for plasma low density lipoprotein (LDL) is regulated by a sensitive system of feedback suppression. The number of functional LDL receptors declines by more than 20 fold when cellular stores of esterified cholesterol are increased by incubation of cells with an exogenous source of cholesterol. Fibroblasts from patients with the heterozygous form of familial hypercholesterolemia (FH) possess one functional allele and one nonfunctional allele at the LDL receptor locus. In the current studies, we have examined the effect that this deficiency produces upon the pattern of regulation of the single functional allele at the LDL receptor locus. Under growth conditions that induced a maximal rate of LDL receptor synthesis (that is, growth in the absence of an exogenous source of cholesterol), the FH heterozygote cells produced about one half as many functional LDL receptors as did the normal cells. More importantly, when grown in the presence of increasing amounts of exogenous cholesterol, the FH heterozygote and normal cells suppressed their respective LDL receptor activities in parallel. Over a wide range of LDL receptor activities, at each level of cellular esterified cholesterol, the FH heterozygote cells expressed about one half as many receptors as did the normal cells. These data indicate that in the FH heterozygote cells, the receptor regulatory mechanism dictates that the normal allele produce only the amount of gene product that it would normally produce at a given level of cellular esterified cholesterol. The failure of the regulatory mechanism to stimulate the normal allele at the LDL receptor locus to produce twice its normal amount of gene product leaves the FH heterozygote cells with a persistent 50% deficiency in LDL receptors under all conditions of cell growth."}
{"id": "PMID:184961", "title": "Characterization of a cell culture model for the study of adenosine deaminase- and purine nucleoside phosphorylase-deficient immunologic disease.", "content": "The absence of erythrocytic adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) has been associated with severe immunodeficiency disease in children. We have developed a cell culture model to study the possible relationships between purine salvage enzymes and immunologic function using an established T cell lymphosarcoma (S49) and a potent inhibitor of ADA, erythro-9(2-hydroxy-3-nonyl) adenine (EHNA). Wild-type S49 cells are killed by dexamethasone or dbc AMP, and adenosine (5 muM) in the presence of an ADA inhibitor (6 muM EHNA) also prevents the growth of and kills these S49 cells. It has been proposed that adenosine is toxic to lymphoid cells by virtue of its ability to increase the intracellular concentrations of cyclic AMP. We examined the sensitivity of three mutants of S49 cells, with distinctive defects in some component of cyclic AMP metabolism or action, to killing by adenosine and EHNA. All three mutants are resistant to killing by isoproterenol or cholera toxin and two are resistant to dbc AMP itself, but all are sensitive to killing by adenosine and EHNA. Similarly, two dexamethasone-resistant S49 mutants are as sensitive to adenosine and EHNA as are the wildtype cells. We have also simulated the purine nucleoside phosphorylase deficiency in S49 cells by adding inosine and adenosine to the growth medium. In the presence of EHNA or inosine, the toxic effects of adenosine can be partially reversed by addition of (10-20 muM) uridine, an observation suggesting that adenosine is toxic as the result of its inducing pyrimidine starvation.", "contents": "Characterization of a cell culture model for the study of adenosine deaminase- and purine nucleoside phosphorylase-deficient immunologic disease. The absence of erythrocytic adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) has been associated with severe immunodeficiency disease in children. We have developed a cell culture model to study the possible relationships between purine salvage enzymes and immunologic function using an established T cell lymphosarcoma (S49) and a potent inhibitor of ADA, erythro-9(2-hydroxy-3-nonyl) adenine (EHNA). Wild-type S49 cells are killed by dexamethasone or dbc AMP, and adenosine (5 muM) in the presence of an ADA inhibitor (6 muM EHNA) also prevents the growth of and kills these S49 cells. It has been proposed that adenosine is toxic to lymphoid cells by virtue of its ability to increase the intracellular concentrations of cyclic AMP. We examined the sensitivity of three mutants of S49 cells, with distinctive defects in some component of cyclic AMP metabolism or action, to killing by adenosine and EHNA. All three mutants are resistant to killing by isoproterenol or cholera toxin and two are resistant to dbc AMP itself, but all are sensitive to killing by adenosine and EHNA. Similarly, two dexamethasone-resistant S49 mutants are as sensitive to adenosine and EHNA as are the wildtype cells. We have also simulated the purine nucleoside phosphorylase deficiency in S49 cells by adding inosine and adenosine to the growth medium. In the presence of EHNA or inosine, the toxic effects of adenosine can be partially reversed by addition of (10-20 muM) uridine, an observation suggesting that adenosine is toxic as the result of its inducing pyrimidine starvation."}
{"id": "PMID:184962", "title": "In situ hybridization of repetitive monkey genome sequences isolated from defective simian virus 40 DNA.", "content": "The origin of a repetitive monkey DNA sequence that is incorporated into a defective simian virus 40 genome has been studied. A fragment (about 140 base pairs in length) containing essentially all the repetitive monkey DNA present in the defective and few, if any, SV40 sequences can be cleaved from the purified defective DNA by restriction endonucleases Hind(II and III). Radioactive cRNA prepared with the isolated fragment as template was hybridized in situ to African green monkey chromosomes. The results indicate that all or part of the sequence in question occurs at both centromeric and noncentromeric positions in many, but not all, chromosomes. Of the typical 60 chromosomes, between nine and eleven hybridize with the cRNA in noncentromeric regions.", "contents": "In situ hybridization of repetitive monkey genome sequences isolated from defective simian virus 40 DNA. The origin of a repetitive monkey DNA sequence that is incorporated into a defective simian virus 40 genome has been studied. A fragment (about 140 base pairs in length) containing essentially all the repetitive monkey DNA present in the defective and few, if any, SV40 sequences can be cleaved from the purified defective DNA by restriction endonucleases Hind(II and III). Radioactive cRNA prepared with the isolated fragment as template was hybridized in situ to African green monkey chromosomes. The results indicate that all or part of the sequence in question occurs at both centromeric and noncentromeric positions in many, but not all, chromosomes. Of the typical 60 chromosomes, between nine and eleven hybridize with the cRNA in noncentromeric regions."}
{"id": "PMID:184963", "title": "The arrangement of simian virus 40 sequences in the DNA of transformed cells.", "content": "High molecular weight DNA, isolated from eleven cloned lines of rat cells independently transformed by SV40, was cleaved with various restriction endonucleases. The DNA was fractionated by electrophoresis through agarose gels, denatured in situ, transferred directly to sheets of nitrocellulose as described by Southern (1975), and hybridized to SV40 DNA labeled in vitro to high specific activity. The location of viral sequences among the fragments of transformed cell DNA was determined by autoradiography. The DNAs of seven of the cell lines contained viral sequences in fragments of many different sizes. The remaining four cell lines each contain a single insertion of viral DNA at a different chromosomal location. The junctions between viral and cellular sequences map at different places on the viral genome.", "contents": "The arrangement of simian virus 40 sequences in the DNA of transformed cells. High molecular weight DNA, isolated from eleven cloned lines of rat cells independently transformed by SV40, was cleaved with various restriction endonucleases. The DNA was fractionated by electrophoresis through agarose gels, denatured in situ, transferred directly to sheets of nitrocellulose as described by Southern (1975), and hybridized to SV40 DNA labeled in vitro to high specific activity. The location of viral sequences among the fragments of transformed cell DNA was determined by autoradiography. The DNAs of seven of the cell lines contained viral sequences in fragments of many different sizes. The remaining four cell lines each contain a single insertion of viral DNA at a different chromosomal location. The junctions between viral and cellular sequences map at different places on the viral genome."}
{"id": "PMID:184964", "title": "Resolution of simian virus 40 proteins in whole cell extracts by two-dimensional electrophoresis: heterogeneity of the major capsid protein.", "content": "The major capsid protein (VP1) of simian virus 40 (SV40) has been analyzed by two-dimensional electrophoresis. This system separates protein according to isoelectric point by isoelectric-focusing, and according to molecular weight by sodium dodecylsulphate electrophoresis (O'Farrell, 1975). VP1 synthesis in infected CV-1 cells can be monitored directly by analysis of unfractionated whole cell extracts; the resolution of VP1 from cellular proteins allows its detection as early as 13 hr after infection. The two-dimensional separation of VP1 reveals that it is heterogeneous, consisting of one major protein (molecular weight 47,000 daltons and isoelectric point of approximately pH 6.8) and five minor protein components. The minor forms of VP1 are 10% of the total VP1 and differ from the major form of VP1 both in molecular weight (by approximately 500 daltons) and isoelectric point (ranging from approximately pH 6.7 to pH 6.9). Evidence is presented to show that two of the minor forms are phosphorylated derivatives of VP1, and it is further suggested that all the different forms of VP1 are the result of modifications of the primary product of translation. A temperature-sensitive mutant of the BC complementation group (BC11) of SV40 results in the synthesis of VP1 with an altered electrophoretic mobility; both the major form of VP1  and the minor forms are shifted in their isoelectric points. In addition to the specific case of SV40, two aspects of these studies should be generally significant to investigators studying eucaryotic gene expression by two-dimensional gel electrophoresis: first, the genetic origin of a protein can be determined by a temperature-sensitive mutation which causes a charge change in the resultant protein; and second, two or more protein spots on a two-dimensional separation may be the products of a single gene.", "contents": "Resolution of simian virus 40 proteins in whole cell extracts by two-dimensional electrophoresis: heterogeneity of the major capsid protein. The major capsid protein (VP1) of simian virus 40 (SV40) has been analyzed by two-dimensional electrophoresis. This system separates protein according to isoelectric point by isoelectric-focusing, and according to molecular weight by sodium dodecylsulphate electrophoresis (O'Farrell, 1975). VP1 synthesis in infected CV-1 cells can be monitored directly by analysis of unfractionated whole cell extracts; the resolution of VP1 from cellular proteins allows its detection as early as 13 hr after infection. The two-dimensional separation of VP1 reveals that it is heterogeneous, consisting of one major protein (molecular weight 47,000 daltons and isoelectric point of approximately pH 6.8) and five minor protein components. The minor forms of VP1 are 10% of the total VP1 and differ from the major form of VP1 both in molecular weight (by approximately 500 daltons) and isoelectric point (ranging from approximately pH 6.7 to pH 6.9). Evidence is presented to show that two of the minor forms are phosphorylated derivatives of VP1, and it is further suggested that all the different forms of VP1 are the result of modifications of the primary product of translation. A temperature-sensitive mutant of the BC complementation group (BC11) of SV40 results in the synthesis of VP1 with an altered electrophoretic mobility; both the major form of VP1  and the minor forms are shifted in their isoelectric points. In addition to the specific case of SV40, two aspects of these studies should be generally significant to investigators studying eucaryotic gene expression by two-dimensional gel electrophoresis: first, the genetic origin of a protein can be determined by a temperature-sensitive mutation which causes a charge change in the resultant protein; and second, two or more protein spots on a two-dimensional separation may be the products of a single gene."}
{"id": "PMID:184965", "title": "The 30S Moloney sarcoma virus RNA contains leukemia virus nucleotide sequences.", "content": "The 50S-70S RNA of a Moloney sarcoma-leukemia virus [Mo-MSV(MLV)] complex produced by a particular mouse cell line was shown by gel electrophoresis to contain a major (97%) 30S sarcoma-specific subunit species and a minor (3%) 38S leukemia virus-specific subunit. On the basis of its sedimentation coefficient and known complexity, the 30S Mo-MSV RNA was estimated to be a unique RNA molecule of about 6000 nucleotides. Hybridization experiments using viral RNA and DNA complementary to viral RNA (cDNA) made by viral DNA polymerase indicated that the 30S Mo-MSV RNA shared 70% of its sequences with Mo-MLV, 30% with another MLV derived from Mo-MLV, and 30% with Kirsten sarcoma-xenotropic leukemia virus. The 30S Mo-MSV RNA sequences shared with these viruses were not additive. The Tm of a Mo-MSV RNA-MLV cDNA hybrid was 83 degrees C, indicating that large contiguous nucleotide sequences were shared between the two nucleic acids. Mo-MSV RNA and Mo-MLV RNA shared possibly seven of 20-30 RNAase T1-resistant oligonucleotides, while Mo-MSV RNA contained three, and Mo-MLV RNA contained at least five specific oligonucleotides. We conclude that the 30S Mo-MSV RNA molecule consists of approximately 70% (about 4200 nucleotides) Mo-MLV-specific sequences and of 30% (1800 nucleotides) Mo-MSV-specific sequences covalently linked. Our results favor the hypothesis that 30S Mo-MSV RNA was generated by recombination between Mo-MLV and other genetic elements. We discuss whether all or only the MSV-specific sequences of the 30S Mo-MSV RNA function as sarcoma genes. Mo-MLV cDNA was hybridized about 45% by unfractionated Mo-MSV (MLV) RNA at RNA/DNA ratios of up to 10, about 50% by electrophoretically purified 30S Mo-MSV RNA at RNA/DNA ratios up to 500, but close to 100% by unfractionated Mo-MSV(MLV) RNA at RNA/DNA ratios over 900. This indicated that unfractionated RNA of our Mo-MSV(MLV) contained a complete complement of Mo-MLV, albeit at a low ratio.", "contents": "The 30S Moloney sarcoma virus RNA contains leukemia virus nucleotide sequences. The 50S-70S RNA of a Moloney sarcoma-leukemia virus [Mo-MSV(MLV)] complex produced by a particular mouse cell line was shown by gel electrophoresis to contain a major (97%) 30S sarcoma-specific subunit species and a minor (3%) 38S leukemia virus-specific subunit. On the basis of its sedimentation coefficient and known complexity, the 30S Mo-MSV RNA was estimated to be a unique RNA molecule of about 6000 nucleotides. Hybridization experiments using viral RNA and DNA complementary to viral RNA (cDNA) made by viral DNA polymerase indicated that the 30S Mo-MSV RNA shared 70% of its sequences with Mo-MLV, 30% with another MLV derived from Mo-MLV, and 30% with Kirsten sarcoma-xenotropic leukemia virus. The 30S Mo-MSV RNA sequences shared with these viruses were not additive. The Tm of a Mo-MSV RNA-MLV cDNA hybrid was 83 degrees C, indicating that large contiguous nucleotide sequences were shared between the two nucleic acids. Mo-MSV RNA and Mo-MLV RNA shared possibly seven of 20-30 RNAase T1-resistant oligonucleotides, while Mo-MSV RNA contained three, and Mo-MLV RNA contained at least five specific oligonucleotides. We conclude that the 30S Mo-MSV RNA molecule consists of approximately 70% (about 4200 nucleotides) Mo-MLV-specific sequences and of 30% (1800 nucleotides) Mo-MSV-specific sequences covalently linked. Our results favor the hypothesis that 30S Mo-MSV RNA was generated by recombination between Mo-MLV and other genetic elements. We discuss whether all or only the MSV-specific sequences of the 30S Mo-MSV RNA function as sarcoma genes. Mo-MLV cDNA was hybridized about 45% by unfractionated Mo-MSV (MLV) RNA at RNA/DNA ratios of up to 10, about 50% by electrophoretically purified 30S Mo-MSV RNA at RNA/DNA ratios up to 500, but close to 100% by unfractionated Mo-MSV(MLV) RNA at RNA/DNA ratios over 900. This indicated that unfractionated RNA of our Mo-MSV(MLV) contained a complete complement of Mo-MLV, albeit at a low ratio."}
{"id": "PMID:184966", "title": "On the nature of 5' termini in nuclear pre-mRNA of Ehrlich carcinoma cells.", "content": "5' terminal nucleosides of nuclear pre-mRNA of Ehrlich ascites carcinoma cells were analyzed by a combination of different chromatographic methods and phosphatase treatment. The heavy nuclear pre-mRNA contains mainly unblocked triphosphorylated nucleosides at the 5' end, although some capped 5' ends could also be found. In this respect, it differs from cytoplasmic poly(A)+ mRNA which contains blocked 5' termini and no triphosphorylated ends. The 5' terminal nucleotides in pre-mRNA are pppGp and pppAp (in a ratio of 3:2). The determination of pppNp content in poly (A)+, poly(U)+, and poly (A)-(U)- fragments of RNA has been used as an approach to establish the topography of pre-mRNA. We also established that the technique for isolation of triphosphorylated 5' terminal fragments of RNA based on hydroxyapatite chromatography (Bajsz\u00e1r, Samarina, and Georgiev, 1974) is still valid in the presence of blocked oligonucleotides. The latter do not interfere with fragments containing free triphosphate groups. Using this technique, we showed that a small but significant portion of triphosphorylated 5' end fragments of  100 nucleotides in length contain oligo(U) sequences reacting with poly(A)-Sepharose.", "contents": "On the nature of 5' termini in nuclear pre-mRNA of Ehrlich carcinoma cells. 5' terminal nucleosides of nuclear pre-mRNA of Ehrlich ascites carcinoma cells were analyzed by a combination of different chromatographic methods and phosphatase treatment. The heavy nuclear pre-mRNA contains mainly unblocked triphosphorylated nucleosides at the 5' end, although some capped 5' ends could also be found. In this respect, it differs from cytoplasmic poly(A)+ mRNA which contains blocked 5' termini and no triphosphorylated ends. The 5' terminal nucleotides in pre-mRNA are pppGp and pppAp (in a ratio of 3:2). The determination of pppNp content in poly (A)+, poly(U)+, and poly (A)-(U)- fragments of RNA has been used as an approach to establish the topography of pre-mRNA. We also established that the technique for isolation of triphosphorylated 5' terminal fragments of RNA based on hydroxyapatite chromatography (Bajsz\u00e1r, Samarina, and Georgiev, 1974) is still valid in the presence of blocked oligonucleotides. The latter do not interfere with fragments containing free triphosphate groups. Using this technique, we showed that a small but significant portion of triphosphorylated 5' end fragments of  100 nucleotides in length contain oligo(U) sequences reacting with poly(A)-Sepharose."}
{"id": "PMID:184969", "title": "Repair processes and the response of dividing and non-dividing cells to methyl methanesulphonate and dimethyl sulphate.", "content": "A method for producing a viable non-dividing population of Chinese hamster V79 cells in suspension is described and the characteristics of the population outlined. The stationary population is more sensitive to methylating agents than a similar but exponentially growing population, the increased sensitivity arising from the loss of the shoulder from the survival curve. The extent of reaction of the agent with cellular macromolecules is similar in both cases. The repair capabilities of the two populations was examined. Non-semiconservative DNA repair synthesis occurs whether the cells are in a growth or no-growth condition when insulted. Repair of single-strand breaks, which arise following methylation, also proceeds up to the size of the replicon. The relationship of this stationary population to other no-growth conditions and its utility as a model for carcinogenesis studies is discussed.", "contents": "Repair processes and the response of dividing and non-dividing cells to methyl methanesulphonate and dimethyl sulphate. A method for producing a viable non-dividing population of Chinese hamster V79 cells in suspension is described and the characteristics of the population outlined. The stationary population is more sensitive to methylating agents than a similar but exponentially growing population, the increased sensitivity arising from the loss of the shoulder from the survival curve. The extent of reaction of the agent with cellular macromolecules is similar in both cases. The repair capabilities of the two populations was examined. Non-semiconservative DNA repair synthesis occurs whether the cells are in a growth or no-growth condition when insulted. Repair of single-strand breaks, which arise following methylation, also proceeds up to the size of the replicon. The relationship of this stationary population to other no-growth conditions and its utility as a model for carcinogenesis studies is discussed."}
{"id": "PMID:184970", "title": "Biochemical changes after hepatic injury by allyl alcohol and N-hydroxy-2-acetylaminofluorene.", "content": "Administration of hepatotoxic doses of allyl alcohol and N-hydroxy-2-acetylaminofluorene (N-OH-AAF) TO adult male rats produced periportal necrosis and functional derangement of the hepatic endoplasmic reticulum within 24 h. The rates of N-demethylation of ethylmorphine and p-hydroxylation of aniline were decreased 6 h following allyl alcohol administration, but cytochromes P-450 and b5 were unchanged. In contrast, administration of NOH-AAF decreased cytochromes P-450 and b5 and the rate of aniline p-hydroxylation, but did not change the rate of N-demethylation of ethylmorphine or the activities of cytochrome c reductase and glucose-6-phosphatase. No decrease was observed in the activity of the cytosol enzyme, DT diaphorase, following allyl alcohol treatment. The changes by these periportal hepatotoxins were compared with those produced both by central and midzonal hepatotoxins and with changes occurring in the liver after surgical partial hepatectomy.", "contents": "Biochemical changes after hepatic injury by allyl alcohol and N-hydroxy-2-acetylaminofluorene. Administration of hepatotoxic doses of allyl alcohol and N-hydroxy-2-acetylaminofluorene (N-OH-AAF) TO adult male rats produced periportal necrosis and functional derangement of the hepatic endoplasmic reticulum within 24 h. The rates of N-demethylation of ethylmorphine and p-hydroxylation of aniline were decreased 6 h following allyl alcohol administration, but cytochromes P-450 and b5 were unchanged. In contrast, administration of NOH-AAF decreased cytochromes P-450 and b5 and the rate of aniline p-hydroxylation, but did not change the rate of N-demethylation of ethylmorphine or the activities of cytochrome c reductase and glucose-6-phosphatase. No decrease was observed in the activity of the cytosol enzyme, DT diaphorase, following allyl alcohol treatment. The changes by these periportal hepatotoxins were compared with those produced both by central and midzonal hepatotoxins and with changes occurring in the liver after surgical partial hepatectomy."}
{"id": "PMID:184974", "title": "Substrate specificity of tonin from rat submaxillary gland.", "content": "The substrate specificity of tonin from rat submaxillary gland was examined with a series of synthetic peptides encompassing the C-terminus of the decapeptide substrate angiotensin I. In contrast to angiotensin I-converting enzyme from plasma or lung, only angiotensin I, (des-Asp1)-angiotensin I, and (des-Asp1, des-Arg2)-angiotensin I are substrates of tonin with Km values of 34.5 muM, 39.3 muM, and 54.4 muM, respectively, while the shorter C-terminal peptides are not hydrolyzed. Thus, the N-terminal sequence extending from position 1 to 3 is the enzymatic binding site for tonin. Turnover numbers of 33.4 sec-1, 42.8 sec-1, and 6.5 sec-1 are observed for the hydrolysis of angiotensin I, (des-Asp1)-angiotensin I, and (des-Asp1, des-Arg2)-angiotensin I, respectively. The relative percentage rates of hydrolysis (proportional to V/Km) at low substrate concentrations ([S] less than less than Km) are almost identical for (des-Asp1)-angiotensin I, angiotensin I, and the tetradecapeptide substrate, indicating that these three peptides are equally good substrates at low physiological concentrations. The observed high specificity of the enzyme lends support to the possible important role of tonin for local conversion in tissue. The conversion of (des-Asp1)-angiotensin I to (des-Asp1)-angiotensin II (angiotensin III) is of particular interest in relation to the recently suggested, potential role of the latter peptide in aldosterone release.", "contents": "Substrate specificity of tonin from rat submaxillary gland. The substrate specificity of tonin from rat submaxillary gland was examined with a series of synthetic peptides encompassing the C-terminus of the decapeptide substrate angiotensin I. In contrast to angiotensin I-converting enzyme from plasma or lung, only angiotensin I, (des-Asp1)-angiotensin I, and (des-Asp1, des-Arg2)-angiotensin I are substrates of tonin with Km values of 34.5 muM, 39.3 muM, and 54.4 muM, respectively, while the shorter C-terminal peptides are not hydrolyzed. Thus, the N-terminal sequence extending from position 1 to 3 is the enzymatic binding site for tonin. Turnover numbers of 33.4 sec-1, 42.8 sec-1, and 6.5 sec-1 are observed for the hydrolysis of angiotensin I, (des-Asp1)-angiotensin I, and (des-Asp1, des-Arg2)-angiotensin I, respectively. The relative percentage rates of hydrolysis (proportional to V/Km) at low substrate concentrations ([S] less than less than Km) are almost identical for (des-Asp1)-angiotensin I, angiotensin I, and the tetradecapeptide substrate, indicating that these three peptides are equally good substrates at low physiological concentrations. The observed high specificity of the enzyme lends support to the possible important role of tonin for local conversion in tissue. The conversion of (des-Asp1)-angiotensin I to (des-Asp1)-angiotensin II (angiotensin III) is of particular interest in relation to the recently suggested, potential role of the latter peptide in aldosterone release."}
{"id": "PMID:184975", "title": "Quantification of human atrioventricular nodal concealed conduction utilizing S1S2S3 stimulation.", "content": "We studied antegrade concealed conduction of atrial extrastimuli (A2) that blocked in the atrioventricular (AV) node in eight subjects, using a third extrastimulus (A3), coupled at decreasing coupling intervals to A2. Three A1-A2 intervals were tested in each subject: late (just shorter than AV nodal effective refractory period), intermediate, and early (just longer than atrial functional refractory period). The curves relating the following variables were constructed for each A2: A1-A3, H1-H3 and A2-A3, A3-H3. The former was compared to the control A1-A2, H1-H2 curve. Concealment of A2 was demonstrated in all eight subjects at the three tested values of A1-A2. The A2-A3, A3-H3 curve allowed analysis of AV nodal conduction time (A3-H3) and AV nodal recovery time (defined as the shortest A2-A3 at which the impulse conducted to the His bundle) at identical values of A2-A3. In all subjects the timing of blocked A2 had minimal effect on both AV nodal conduction time and recovery time. In five of the eight subjects a late A2 sporadically conducted to the His bundle. Conduction of A2 to the His bundle resulted in marked lengthening of both AV nodal conduction and recovery times. Concealed conduction of A2 was always demonstrated, but the degree of concealment was relatively fixed, whether A2 was an early, intermediate, or late blocked premature beat. Slow conduction of A2 had a much greater effect than concealment of A2 on subsequent impulse conduction.", "contents": "Quantification of human atrioventricular nodal concealed conduction utilizing S1S2S3 stimulation. We studied antegrade concealed conduction of atrial extrastimuli (A2) that blocked in the atrioventricular (AV) node in eight subjects, using a third extrastimulus (A3), coupled at decreasing coupling intervals to A2. Three A1-A2 intervals were tested in each subject: late (just shorter than AV nodal effective refractory period), intermediate, and early (just longer than atrial functional refractory period). The curves relating the following variables were constructed for each A2: A1-A3, H1-H3 and A2-A3, A3-H3. The former was compared to the control A1-A2, H1-H2 curve. Concealment of A2 was demonstrated in all eight subjects at the three tested values of A1-A2. The A2-A3, A3-H3 curve allowed analysis of AV nodal conduction time (A3-H3) and AV nodal recovery time (defined as the shortest A2-A3 at which the impulse conducted to the His bundle) at identical values of A2-A3. In all subjects the timing of blocked A2 had minimal effect on both AV nodal conduction time and recovery time. In five of the eight subjects a late A2 sporadically conducted to the His bundle. Conduction of A2 to the His bundle resulted in marked lengthening of both AV nodal conduction and recovery times. Concealed conduction of A2 was always demonstrated, but the degree of concealment was relatively fixed, whether A2 was an early, intermediate, or late blocked premature beat. Slow conduction of A2 had a much greater effect than concealment of A2 on subsequent impulse conduction."}
{"id": "PMID:184976", "title": "Electrophysiological observations on the digitalis-potassium interaction in canine Purkinje fibers.", "content": "We studied the effects of elevating potassium concentration on the membrane potential of Purkinje cells exposed to toxic concentrations of acetylstrophanthidin or ouabain. Conventional intracellular microelectrode techniques were employed. Rapid elevation of [K+]o from 2.7 to 5.4 mEq/liter resulted in an initial increase (more negative) in membrane potential of cells demonstrating ouabain-induced phase 4 depolarization. The increase in maximal diastolic potential occurred initially without suppression of phase 4 depolarization. In cells rendered inexcitable by ouabain or acetylstrophanthidin, elevation of [K+]o consistently increased membrane potential and restored excitability. In four experiments automaticity was initiated within 2 minutes after the increase in [K]o. Although automaticity reappeared, as maximal diastolic potential increased, the automatic rate slowed and then pacemaker activity was suppressed. Studies with 3H-ouabain showed that the increase in membrane potential paralleled K+-induced release of 3H-ouabain from Purkinje cells. These studies suggest that elevation of [K+]o reverses digitalis toxic manifestations in canine Purkinje fibers by causing release of cardiac glycosides bound to the membrane. The observed increase in membrane potential of ouabain-treated Purkinje fibers that occurred after [K+]o elevation was considered to be mediated in part by restoration of the Na pump and by electrogenic pumping.", "contents": "Electrophysiological observations on the digitalis-potassium interaction in canine Purkinje fibers. We studied the effects of elevating potassium concentration on the membrane potential of Purkinje cells exposed to toxic concentrations of acetylstrophanthidin or ouabain. Conventional intracellular microelectrode techniques were employed. Rapid elevation of [K+]o from 2.7 to 5.4 mEq/liter resulted in an initial increase (more negative) in membrane potential of cells demonstrating ouabain-induced phase 4 depolarization. The increase in maximal diastolic potential occurred initially without suppression of phase 4 depolarization. In cells rendered inexcitable by ouabain or acetylstrophanthidin, elevation of [K+]o consistently increased membrane potential and restored excitability. In four experiments automaticity was initiated within 2 minutes after the increase in [K]o. Although automaticity reappeared, as maximal diastolic potential increased, the automatic rate slowed and then pacemaker activity was suppressed. Studies with 3H-ouabain showed that the increase in membrane potential paralleled K+-induced release of 3H-ouabain from Purkinje cells. These studies suggest that elevation of [K+]o reverses digitalis toxic manifestations in canine Purkinje fibers by causing release of cardiac glycosides bound to the membrane. The observed increase in membrane potential of ouabain-treated Purkinje fibers that occurred after [K+]o elevation was considered to be mediated in part by restoration of the Na pump and by electrogenic pumping."}
{"id": "PMID:184977", "title": "The effects of iron deficiency on the respiratory function and cytochrome content of rat heart mitochondria.", "content": "We have examined the effects of total body iron deficiency on the function of mitochondria isolated from rat hearts. Male Wistar rats were weaned at 21 days and divided into an experimental iron-deficient group and a control group. Both groups received identical diet but an iron supplement (180 mg of ferrous sulfate per kg of diet) was added for the control group. Rats were studied at 7 and 14 weeks. Iron-deficient rats weighed less than controls but showed significantly increased ventricle to body weight ratio at both 7 and 14 weeks, indicating relative cardiac hypertrophy. Isolated mitochondrial fractions from iron-deficient and control rats contained similar proportions of whole homogenate protein and succinic cytochrome c reductase activity, indicating that the fractions isolated from the experimental and control rats were comparable. In iron-deficient rats NADH cytochrome c reductase, succinic cytochrome c reductase, succinic dehydrogenase, and NADH ferricyanide oxidoreductase activities were all significantly reduced at 7 and 14 weeks. Cytochrome c oxidase activity was significantly reduced only at 14 weeks as were the concentrations of cytochromes a3, c1, and b. The rate of oxygen uptake by mitochondria was significantly lower at both 7 and 14 weeks but the P/O ratio was unaltered. We conclude that iron deficiency is associated with impairment of myocardial mitochondrial electron transport.", "contents": "The effects of iron deficiency on the respiratory function and cytochrome content of rat heart mitochondria. We have examined the effects of total body iron deficiency on the function of mitochondria isolated from rat hearts. Male Wistar rats were weaned at 21 days and divided into an experimental iron-deficient group and a control group. Both groups received identical diet but an iron supplement (180 mg of ferrous sulfate per kg of diet) was added for the control group. Rats were studied at 7 and 14 weeks. Iron-deficient rats weighed less than controls but showed significantly increased ventricle to body weight ratio at both 7 and 14 weeks, indicating relative cardiac hypertrophy. Isolated mitochondrial fractions from iron-deficient and control rats contained similar proportions of whole homogenate protein and succinic cytochrome c reductase activity, indicating that the fractions isolated from the experimental and control rats were comparable. In iron-deficient rats NADH cytochrome c reductase, succinic cytochrome c reductase, succinic dehydrogenase, and NADH ferricyanide oxidoreductase activities were all significantly reduced at 7 and 14 weeks. Cytochrome c oxidase activity was significantly reduced only at 14 weeks as were the concentrations of cytochromes a3, c1, and b. The rate of oxygen uptake by mitochondria was significantly lower at both 7 and 14 weeks but the P/O ratio was unaltered. We conclude that iron deficiency is associated with impairment of myocardial mitochondrial electron transport."}
{"id": "PMID:184978", "title": "Hay fever treated with ACTH gel.", "content": "ACTH gel was used as a treatment for hay fever during the 1972-1974 hay fever seasons. Patients suffering from hay fever were given ACTH in different dose schedules and other hay fever patients were used as controls. Subjectively, those treated with ACTH gel were pleased with the results and reported more favourably on the injections than those receiving placebo. Objectively, using presence of any symptoms as the index of measurement, those treated with ACTH gel (80 units once weekly or 80 units twice weekly) had a significantly lower incidence of hay fever. Side effects were few.", "contents": "Hay fever treated with ACTH gel. ACTH gel was used as a treatment for hay fever during the 1972-1974 hay fever seasons. Patients suffering from hay fever were given ACTH in different dose schedules and other hay fever patients were used as controls. Subjectively, those treated with ACTH gel were pleased with the results and reported more favourably on the injections than those receiving placebo. Objectively, using presence of any symptoms as the index of measurement, those treated with ACTH gel (80 units once weekly or 80 units twice weekly) had a significantly lower incidence of hay fever. Side effects were few."}
{"id": "PMID:184979", "title": "Superoxide anion independent reduction of nitrobluetetrazolium by human renal tissue.", "content": "The rate of nitrobluetetrazolium reduction by extracts from rodent and human kidney tissue has been measured in the presence and absence of exogeneous superoxide dismutase and catalase. These oxygen metabolite scavengers had no effect on that reduction rate. Oxygen was inhibitory to nitrobluetetrazolium reduction whereas anaerobiosis enhanced the rate. These data suggest that the reduction rate in renal tissue is not superoxide anion radical mediated as had been previously suggested.", "contents": "Superoxide anion independent reduction of nitrobluetetrazolium by human renal tissue. The rate of nitrobluetetrazolium reduction by extracts from rodent and human kidney tissue has been measured in the presence and absence of exogeneous superoxide dismutase and catalase. These oxygen metabolite scavengers had no effect on that reduction rate. Oxygen was inhibitory to nitrobluetetrazolium reduction whereas anaerobiosis enhanced the rate. These data suggest that the reduction rate in renal tissue is not superoxide anion radical mediated as had been previously suggested."}
{"id": "PMID:184980", "title": "Detection of inhibitors in reduced nicotinamide adenine dinucleotide by kinetic methods.", "content": "Methods are described for detection of lactate dehydrogenase (LDH) inhibitors in preparations of reduced nicotinamide adenine dinucleotide. They are (a) comparison of values by kinetic methods with those measured for highly purified NADH and (b) examination of Lineweaver-Burk plots. Chromatographic inhomogeneities are correlated with deviant values for the kinetic constants of NADH preparations. Lineweaver-Burk plots that curve upward at the high concentrations or have a larger or smaller than normal slope may indicate the presence of inhibitor. As determined in bicarbonate buffer (0.11 mol/liter, pH 7.9) by use of 0.600 mmol/liter pyruvate and NADH freshly separated from impurities by chromatography on diethyl-aminoethyl-cellulose, the Km (apparent) of NADH at 25 degrees C has the value 8.11 +/- 0.71 mumol/liter (SD, n = 28) with LDH-1 (pig heart, 2.48 +/- 0.05 U per milliliter of reaction mixture, or 41.3 +/- 0.8 nmol/liter per second). Under similar conditions, the Km (apparent) of NADH has the value of 8.57 +/- 1.58 mol/liter (SD, n = 21) with LDH-5 (pig muscle, 1.77 +/- 0.03 U/ml of reaction mixture), or 29.4 +/- 0.6 nmol/liter per second). At infinite substrate concentrations with the same pH, buffer, and temperature, the Km (apparent) for NADH was 26.0 +/- 0.63 mumol/liter with LDH-1 and 23.2 +/- 4.6 mumol/liter with LDH-5.", "contents": "Detection of inhibitors in reduced nicotinamide adenine dinucleotide by kinetic methods. Methods are described for detection of lactate dehydrogenase (LDH) inhibitors in preparations of reduced nicotinamide adenine dinucleotide. They are (a) comparison of values by kinetic methods with those measured for highly purified NADH and (b) examination of Lineweaver-Burk plots. Chromatographic inhomogeneities are correlated with deviant values for the kinetic constants of NADH preparations. Lineweaver-Burk plots that curve upward at the high concentrations or have a larger or smaller than normal slope may indicate the presence of inhibitor. As determined in bicarbonate buffer (0.11 mol/liter, pH 7.9) by use of 0.600 mmol/liter pyruvate and NADH freshly separated from impurities by chromatography on diethyl-aminoethyl-cellulose, the Km (apparent) of NADH at 25 degrees C has the value 8.11 +/- 0.71 mumol/liter (SD, n = 28) with LDH-1 (pig heart, 2.48 +/- 0.05 U per milliliter of reaction mixture, or 41.3 +/- 0.8 nmol/liter per second). Under similar conditions, the Km (apparent) of NADH has the value of 8.57 +/- 1.58 mol/liter (SD, n = 21) with LDH-5 (pig muscle, 1.77 +/- 0.03 U/ml of reaction mixture), or 29.4 +/- 0.6 nmol/liter per second). At infinite substrate concentrations with the same pH, buffer, and temperature, the Km (apparent) for NADH was 26.0 +/- 0.63 mumol/liter with LDH-1 and 23.2 +/- 4.6 mumol/liter with LDH-5."}
{"id": "PMID:184981", "title": "Automated radioimmunoassay of choriomammotropin (human placental lactogen).", "content": "We describe a totally automated procedure for radioimmunoassay of choriomammotropin, in which all phases of the assay are automated in a single system (\"Centria\"). This system permits the simultaneous incubation and separation of many samples in a nonequilibrium assay, and measurements are obtained in less than 30 min. Results for clinical samples by reference radioimmunossay methodology and with the Centria system compared uniformly well: y=0.91x - 0.87;r=0.94. The coefficient of variation for samples run in duplicate on the same day was 5.2%, 7.4% for samples run on different days. The specificity, sensitivity, simplicity, and speed of this system makes it a useful new tool for kinetic, nonequilibrium immunoassay.", "contents": "Automated radioimmunoassay of choriomammotropin (human placental lactogen). We describe a totally automated procedure for radioimmunoassay of choriomammotropin, in which all phases of the assay are automated in a single system (\"Centria\"). This system permits the simultaneous incubation and separation of many samples in a nonequilibrium assay, and measurements are obtained in less than 30 min. Results for clinical samples by reference radioimmunossay methodology and with the Centria system compared uniformly well: y=0.91x - 0.87;r=0.94. The coefficient of variation for samples run in duplicate on the same day was 5.2%, 7.4% for samples run on different days. The specificity, sensitivity, simplicity, and speed of this system makes it a useful new tool for kinetic, nonequilibrium immunoassay."}
{"id": "PMID:184982", "title": "Bile acid and detergent interaction with radioassays based on coated charcoal.", "content": "We tested the radioassays for cyclic AMP and human gastrin, both involving separation on coated charcoal, for interaction with bile acids and detergents, and found a concentration-dependent interaction of taurocholic and glycocholic acid as well as of the surfactant Triton X-100 and sodium laurylsulfate in both assays. The interaction was detectable from concentrations of 0.5 mmol of bile acid per liter or 625 mg of detergent per liter, giving rise to falsely decreased gastrin values and falsely increased or decreased values for cyclic AMP. The interactions demonstrated may be a general effect on all radioassays that are based on the use of coated charcoal in the separation of free from bound ligands.", "contents": "Bile acid and detergent interaction with radioassays based on coated charcoal. We tested the radioassays for cyclic AMP and human gastrin, both involving separation on coated charcoal, for interaction with bile acids and detergents, and found a concentration-dependent interaction of taurocholic and glycocholic acid as well as of the surfactant Triton X-100 and sodium laurylsulfate in both assays. The interaction was detectable from concentrations of 0.5 mmol of bile acid per liter or 625 mg of detergent per liter, giving rise to falsely decreased gastrin values and falsely increased or decreased values for cyclic AMP. The interactions demonstrated may be a general effect on all radioassays that are based on the use of coated charcoal in the separation of free from bound ligands."}
{"id": "PMID:184984", "title": "Creatine kinase in serum: 2. Interference of adenylate kinase with the assay.", "content": "Interference of adenylate kinase with Oliver's method [Biochem. J. 61, 116 (1955)] for creatine kinase is usually suppressed by including an adenylate kinase inhibitor, AMP. We studied the kinetics and compared the inhibition capacities of AMP and diadenosine pentaphosphate. Both are competitive inhibitors, AMP being markedly weaker, with a Ki of about 300 mumol/liter for adenylate kinase from erythrocyte, muscle, and liver. AMP also weakly inhibitis creatine kinase. Diadenosine pentaphosphate inhibits erythrocyte and muscle adenylate kinase strongly (Ki about 0.03 mumol/liter), the liver isoenzyme less strongly (Ki about 3 mumol/liter), and has no effect on creatine kinase up to 100 mumol/liter. All three adenylate kinases may be present in a patinet's serum, causing sample blanks to be high in a creatine kinase assay that lacks inhibitors. In acute hepatic damage, liver adenylate kinase activity in serum can be grossly increased. Use of sufficient diadenosine pentaphosphate alone for complete inhibition is relatively expensive. Consequently, we recommend a combination of both inhibitors. Diadenosine pentaphosphate, 10 mumol, combined with 5 mmol of AMP per liter inhibits adenylate kinase from erythrocytes and muscle by 97% and from liver by 95%.", "contents": "Creatine kinase in serum: 2. Interference of adenylate kinase with the assay. Interference of adenylate kinase with Oliver's method [Biochem. J. 61, 116 (1955)] for creatine kinase is usually suppressed by including an adenylate kinase inhibitor, AMP. We studied the kinetics and compared the inhibition capacities of AMP and diadenosine pentaphosphate. Both are competitive inhibitors, AMP being markedly weaker, with a Ki of about 300 mumol/liter for adenylate kinase from erythrocyte, muscle, and liver. AMP also weakly inhibitis creatine kinase. Diadenosine pentaphosphate inhibits erythrocyte and muscle adenylate kinase strongly (Ki about 0.03 mumol/liter), the liver isoenzyme less strongly (Ki about 3 mumol/liter), and has no effect on creatine kinase up to 100 mumol/liter. All three adenylate kinases may be present in a patinet's serum, causing sample blanks to be high in a creatine kinase assay that lacks inhibitors. In acute hepatic damage, liver adenylate kinase activity in serum can be grossly increased. Use of sufficient diadenosine pentaphosphate alone for complete inhibition is relatively expensive. Consequently, we recommend a combination of both inhibitors. Diadenosine pentaphosphate, 10 mumol, combined with 5 mmol of AMP per liter inhibits adenylate kinase from erythrocytes and muscle by 97% and from liver by 95%."}
{"id": "PMID:184985", "title": "Nature of the interaction between low-density lipoproteins and polyanions and metal ions, as exemplified by heparin and Ca2+.", "content": "I examined the effect of lipid concentration on the interaction of the very-low density and low-density  lipoproteins in serum with heparin and calcium. A precipitate forms when partly delipidated serum is subjected to the polyanion-metal ion system. Although this precipitate is less turbid than the complexed lipoprotein-polyanion-metal ion in undelipidated serum, the two precipitates contain identical amounts of apolipoprotein. Totally delipidated serum produces only a slight precipitate with heparin and calcium, and this precipitate contains only a fraction of the appolipoproteins. Cholesterol and triglycerides are the major determinants of turbidity when serum is mixed with heparin and calcium, but have no effect on the precipitation of the protein moiety. Phospholipids contribute a small proportion of the turbidity in the lipoprotein-polyanion-metal ion interaction. Precipitation of the low-density lipoproteins by heparin and calcium depends on the protein moiety and on the chemical composition of the lipid moiety. Phospholipid is required, but cholesterol and triglyceride are not, for total precipitation of the complex.", "contents": "Nature of the interaction between low-density lipoproteins and polyanions and metal ions, as exemplified by heparin and Ca2+. I examined the effect of lipid concentration on the interaction of the very-low density and low-density  lipoproteins in serum with heparin and calcium. A precipitate forms when partly delipidated serum is subjected to the polyanion-metal ion system. Although this precipitate is less turbid than the complexed lipoprotein-polyanion-metal ion in undelipidated serum, the two precipitates contain identical amounts of apolipoprotein. Totally delipidated serum produces only a slight precipitate with heparin and calcium, and this precipitate contains only a fraction of the appolipoproteins. Cholesterol and triglycerides are the major determinants of turbidity when serum is mixed with heparin and calcium, but have no effect on the precipitation of the protein moiety. Phospholipids contribute a small proportion of the turbidity in the lipoprotein-polyanion-metal ion interaction. Precipitation of the low-density lipoproteins by heparin and calcium depends on the protein moiety and on the chemical composition of the lipid moiety. Phospholipid is required, but cholesterol and triglyceride are not, for total precipitation of the complex."}
{"id": "PMID:184986", "title": "Plasma high-density lipoprotein cholesterol concentrations determined after removal of other lipoproteins by heparin/manganese precipitation or by ultracentrifugation.", "content": "The widely used heparin/MnCl2 precipitation procedure for determination of plasma high-density lipoprotein cholesterol has been re-examined in light of recent reports that isolated preparations of the lipoprotein are only partly precipitated under the test conditions. In the present study, the procedure as applied to plasma tolerated rather wide variations in heparin and MnCl2 concentrations without significant effects on the assayed values in several plasma pools tested. The procedure was further tested on 129 individual samples by comparison with an ultracentrifugal method in which high-density lipoprotein-cholesterol is assumed to be represented by the cholesterol content of the plasma fraction of relative (to water) density greater than 1.063. Our results indicate that high-density lipoprotein is not precipitated under the test conditions when applied to unfractionated plasma.", "contents": "Plasma high-density lipoprotein cholesterol concentrations determined after removal of other lipoproteins by heparin/manganese precipitation or by ultracentrifugation. The widely used heparin/MnCl2 precipitation procedure for determination of plasma high-density lipoprotein cholesterol has been re-examined in light of recent reports that isolated preparations of the lipoprotein are only partly precipitated under the test conditions. In the present study, the procedure as applied to plasma tolerated rather wide variations in heparin and MnCl2 concentrations without significant effects on the assayed values in several plasma pools tested. The procedure was further tested on 129 individual samples by comparison with an ultracentrifugal method in which high-density lipoprotein-cholesterol is assumed to be represented by the cholesterol content of the plasma fraction of relative (to water) density greater than 1.063. Our results indicate that high-density lipoprotein is not precipitated under the test conditions when applied to unfractionated plasma."}
{"id": "PMID:184987", "title": "Evaluation of enzyme-multiplied immunoassay technique (EMIT) for determination of serum digoxin.", "content": "Sixty-seven digoxin-containing sera were analyzed by both radioimmunoassay and EMIT. After some important modifications of the EMIT method, agreement between the two methods was very good. Reproducibility of the EMIT assay was excellent; daily variations in values found for control sera were quite small, and recovery of added digoxin was good. Slight hemolysis hadnegligible effects, but highly hemolyzed specimens gave low recoveries of digoxin.", "contents": "Evaluation of enzyme-multiplied immunoassay technique (EMIT) for determination of serum digoxin. Sixty-seven digoxin-containing sera were analyzed by both radioimmunoassay and EMIT. After some important modifications of the EMIT method, agreement between the two methods was very good. Reproducibility of the EMIT assay was excellent; daily variations in values found for control sera were quite small, and recovery of added digoxin was good. Slight hemolysis hadnegligible effects, but highly hemolyzed specimens gave low recoveries of digoxin."}
{"id": "PMID:184988", "title": "Gas chromatographic determination of urinary vanilglycolic acid, vanilglycol, vanilacetic acid and vanillactic acid-chemical parameters for the diagnosis of neurogenic tumours and the evaluation of their treatment.", "content": "A gas chromatographic method is described for the determination of urinary vanilglycolic acid, vanilglycol, vanilacetic acid and vanillactic acid as their trimethylsilyl derivatives. These metabolites are chemical parameters for the dignosis of neurogenic tumours. Their determination is especially recommended in order to evaluate the effect of the therapy. Results in normals and controls are given. Data in a number of selected patients with neuroblastoma, ganglioneuroma and phaeochromocytoma are presented and discussed.", "contents": "Gas chromatographic determination of urinary vanilglycolic acid, vanilglycol, vanilacetic acid and vanillactic acid-chemical parameters for the diagnosis of neurogenic tumours and the evaluation of their treatment. A gas chromatographic method is described for the determination of urinary vanilglycolic acid, vanilglycol, vanilacetic acid and vanillactic acid as their trimethylsilyl derivatives. These metabolites are chemical parameters for the dignosis of neurogenic tumours. Their determination is especially recommended in order to evaluate the effect of the therapy. Results in normals and controls are given. Data in a number of selected patients with neuroblastoma, ganglioneuroma and phaeochromocytoma are presented and discussed."}
{"id": "PMID:184989", "title": "A rapid method for the estimation of beta-galactocerebrosidase, beta-glucocerebrosidase and sphingomyelinase activities in leukocytes.", "content": "A method for the assay of leukocyte beta-galactocerebrosidase, beta-glucocerebrosidase and sphingomyelinase activities has been developed, based on the separation of the tritiated sphingolipid substrates from their corresponding radioactive hydrophobic product (ceramide) by thin-layer chromatography on Silica gel H coated microscope slides. For the determination of beta-galactocerebrosidase and beta-glucocerebrosidase activities the silica gel is impregnanted with sodium tetraborate. Each chromatogram is easily divided into two distinct zones and the radioactivity content of each is determined by liquid scintillation counting. The technique described, is rapid, less costly than conventional methods and provides an accurate assessment of sphingolipid hydrolase activity. It is suggested that it should be of considerable value in those areas which require the rapid analysis of large numbers of samples, such as in screening for the sphingolipidoses or for enzyme purification studies.", "contents": "A rapid method for the estimation of beta-galactocerebrosidase, beta-glucocerebrosidase and sphingomyelinase activities in leukocytes. A method for the assay of leukocyte beta-galactocerebrosidase, beta-glucocerebrosidase and sphingomyelinase activities has been developed, based on the separation of the tritiated sphingolipid substrates from their corresponding radioactive hydrophobic product (ceramide) by thin-layer chromatography on Silica gel H coated microscope slides. For the determination of beta-galactocerebrosidase and beta-glucocerebrosidase activities the silica gel is impregnanted with sodium tetraborate. Each chromatogram is easily divided into two distinct zones and the radioactivity content of each is determined by liquid scintillation counting. The technique described, is rapid, less costly than conventional methods and provides an accurate assessment of sphingolipid hydrolase activity. It is suggested that it should be of considerable value in those areas which require the rapid analysis of large numbers of samples, such as in screening for the sphingolipidoses or for enzyme purification studies."}
{"id": "PMID:184990", "title": "Biokinetics of galactose in the homozygotes and heterozygotes of both forms of galactosemia.", "content": "41 heterozygoes and 4 homozygotes with a deficiency of galactose 1-phosphate uridyl transferase and also 3 heterozygotes and 1 homozygous patient with galactokinase deficiency were subjected to intravenous galactose loading tests with a dose of 350 mg/kg body weight in order to answer the question whether it is possible to detect the heterozygotes of both types of galactosemia by this method. For comparison, 38 healthy children and adolescents, 24 children with epidemic hepatitis and 4 children with cirrhosis of the liver, which was verified by histology, were included in the study. The elimination half-life (and also the other pharmacokinetic parameters as inaugurated by Dost) was the same for all the heterozygotes for both types of galactosemia almost without exception, and for the healthy cs, children in the acute stages of hepatitis and patients with cirrhosis of the liver was prolonged 2 to 5 times the normal. In patients with hepatitis, however, the elimination half-life was normal before the transaminases. Accordingly, the galactose clearance was decreased to half and one-fourth of the normal. Hence, heterozygotes with galactosemia cannot be detected with galactose loading tests.", "contents": "Biokinetics of galactose in the homozygotes and heterozygotes of both forms of galactosemia. 41 heterozygoes and 4 homozygotes with a deficiency of galactose 1-phosphate uridyl transferase and also 3 heterozygotes and 1 homozygous patient with galactokinase deficiency were subjected to intravenous galactose loading tests with a dose of 350 mg/kg body weight in order to answer the question whether it is possible to detect the heterozygotes of both types of galactosemia by this method. For comparison, 38 healthy children and adolescents, 24 children with epidemic hepatitis and 4 children with cirrhosis of the liver, which was verified by histology, were included in the study. The elimination half-life (and also the other pharmacokinetic parameters as inaugurated by Dost) was the same for all the heterozygotes for both types of galactosemia almost without exception, and for the healthy cs, children in the acute stages of hepatitis and patients with cirrhosis of the liver was prolonged 2 to 5 times the normal. In patients with hepatitis, however, the elimination half-life was normal before the transaminases. Accordingly, the galactose clearance was decreased to half and one-fourth of the normal. Hence, heterozygotes with galactosemia cannot be detected with galactose loading tests."}
{"id": "PMID:184994", "title": "Acute intravascular hemolysis with minimal renal impairment in Clostridium perfringens infection.", "content": "We report here a case of post-abortal clostridium prefringens infection in which there was severe intravascular hemolysis with black urine, but only minor abnormalities of the clotting mechanism and mild renal failure. The patient recovered following supportive therapy only.", "contents": "Acute intravascular hemolysis with minimal renal impairment in Clostridium perfringens infection. We report here a case of post-abortal clostridium prefringens infection in which there was severe intravascular hemolysis with black urine, but only minor abnormalities of the clotting mechanism and mild renal failure. The patient recovered following supportive therapy only."}
{"id": "PMID:184992", "title": "The interrelationships between antidiuretic hormone, adenyl cyclase, tissue cyclic AMP and diffusional water permeability.", "content": "1. Physiological concentrations of antidiuretic hormone increase diffusional water permeability but not measurable cyclic AMP content in the isolated papilla of the rat's kidney. 2. Theophylline (6 mM) increases diffusional water permeability and cyclic AMP content in the isolated papilla of the rat's kidney. 3. The increase in water permeability is detected with 5 muunits.ml-1 of ADH and is maximal with 50 muunits.ml-1. The same maximum was achieved with 6 mM theophylline. 4. Cyclic AMP and dibutyryl cyclic AMP both increase water permeability, but to a lesser extent than theophylline or ADH. 5. In the presence of theophylline, ADH causes a dose related generation of tissue cyclic AMP up to a dose of 2,000,000 muunits.ml-1. 6. Adenyl cyclase is increasingly activated by ADH up to doses of 2,000,000 muunits.ml-1. 7. These results suggest that while ADH activates the adenyl cyclase system and changes water permeability there are sufficient disparities to cast doubt on an exclusive role for cyclic AMP as the second messenger.", "contents": "The interrelationships between antidiuretic hormone, adenyl cyclase, tissue cyclic AMP and diffusional water permeability. 1. Physiological concentrations of antidiuretic hormone increase diffusional water permeability but not measurable cyclic AMP content in the isolated papilla of the rat's kidney. 2. Theophylline (6 mM) increases diffusional water permeability and cyclic AMP content in the isolated papilla of the rat's kidney. 3. The increase in water permeability is detected with 5 muunits.ml-1 of ADH and is maximal with 50 muunits.ml-1. The same maximum was achieved with 6 mM theophylline. 4. Cyclic AMP and dibutyryl cyclic AMP both increase water permeability, but to a lesser extent than theophylline or ADH. 5. In the presence of theophylline, ADH causes a dose related generation of tissue cyclic AMP up to a dose of 2,000,000 muunits.ml-1. 6. Adenyl cyclase is increasingly activated by ADH up to doses of 2,000,000 muunits.ml-1. 7. These results suggest that while ADH activates the adenyl cyclase system and changes water permeability there are sufficient disparities to cast doubt on an exclusive role for cyclic AMP as the second messenger."}
{"id": "PMID:184993", "title": "The effect of pregnancy on mineralo- and gluco-corticoid secretion in the sheep.", "content": "1. The peripheral blood concentrations of aldosterone, corticosterone and cortisol were measured during pregnancy in conscious, undisturbed sheep. 2. Aldosterone levels did not change during pregnancy and the mean pregnant value, 1-2 s.d. 1-4 ng/100 ml(n = 12) was not significantly different from the non-pregnant value, 2-1 s.d. 1-7 (n = 16). 3. Cortisol levels likewise were unchanged by pregnancy-non-pregnant values were 0-56 s.d. 0-50 mug/100 ml (n = 12) compared with 0-46 s.d. 0-40 mug/100 ml (n = 16) in pregnant sheep. 4. Sheep of 110-140 days gestation had a 400 mmol greater total exchangeable sodium than non-pregnant sheep. Plasma volume and plasma renin concentration tended to be elevated near to term. 5. Very high aldosterone secretion rates and peripheral blood levels could be produced in pregnant sheep by stress, intravenous ACTH or angiotensin II infusions, and by sodium deficiency. It is suggested that the pregnant sheep may show increased sensitivity in contrast to non-pregnant sheep to these stimuli and the enlarged size of their adrenals may be a contributing factor.", "contents": "The effect of pregnancy on mineralo- and gluco-corticoid secretion in the sheep. 1. The peripheral blood concentrations of aldosterone, corticosterone and cortisol were measured during pregnancy in conscious, undisturbed sheep. 2. Aldosterone levels did not change during pregnancy and the mean pregnant value, 1-2 s.d. 1-4 ng/100 ml(n = 12) was not significantly different from the non-pregnant value, 2-1 s.d. 1-7 (n = 16). 3. Cortisol levels likewise were unchanged by pregnancy-non-pregnant values were 0-56 s.d. 0-50 mug/100 ml (n = 12) compared with 0-46 s.d. 0-40 mug/100 ml (n = 16) in pregnant sheep. 4. Sheep of 110-140 days gestation had a 400 mmol greater total exchangeable sodium than non-pregnant sheep. Plasma volume and plasma renin concentration tended to be elevated near to term. 5. Very high aldosterone secretion rates and peripheral blood levels could be produced in pregnant sheep by stress, intravenous ACTH or angiotensin II infusions, and by sodium deficiency. It is suggested that the pregnant sheep may show increased sensitivity in contrast to non-pregnant sheep to these stimuli and the enlarged size of their adrenals may be a contributing factor."}
{"id": "PMID:184997", "title": "Control of pain by direct electrical stimulation of peripheral nerves.", "content": "Our results after implanting electrodes around peripheral nerves in 69 patients over a 10 year period are only fair with but 17 individuals maintaining relief until death or until the present time. Thirteen others had weeks or months of temporary relief. A continuing use of transcutaneous and better still of percutaneous electrodes to guide the decision regarding implantation is almost certainly advisable. Intensive efforts in laboratory animal studies with models of chronic pain are needed to improve our understanding of exactly what we should be doing. Empirical sustained work with the individual patient is likely to improve the figures we have presented, even in our present state of ignorance.", "contents": "Control of pain by direct electrical stimulation of peripheral nerves. Our results after implanting electrodes around peripheral nerves in 69 patients over a 10 year period are only fair with but 17 individuals maintaining relief until death or until the present time. Thirteen others had weeks or months of temporary relief. A continuing use of transcutaneous and better still of percutaneous electrodes to guide the decision regarding implantation is almost certainly advisable. Intensive efforts in laboratory animal studies with models of chronic pain are needed to improve our understanding of exactly what we should be doing. Empirical sustained work with the individual patient is likely to improve the figures we have presented, even in our present state of ignorance."}
{"id": "PMID:185000", "title": "Effectiveness of intermediate-term use of secobarbital.", "content": "Secobarbital, 100 mg, was evaluated in two separate sleep laboratory drug evaluation studies, each with 4 insomniac patients. In both studies, the effect of secobarbital in inducing and maintaining sleep was evaluated, as well as the effects of the drug on sleep stages. Statistical analysis demonstrated that the results of the two studies could be combined. With short-term drug administration of secobarbital (up to 3 nights), there was an improvement in both sleep induction and sleep maintenance. Total wake time was decreased 43% below baseline and was consistently decreased in each third of the night. With intermediate-term drug administration (2 wk), total wake time was decreased only 14% (not statistically significant). Following drug withdrawal, the degree of sleep difficulty returned to baseline levels. The results indicate that secobarbital 100 mg is effective for short-term use but loses much of its effectiveness with intermediate use and suggest that the drug is of limited value for insomniac patients who require nightly medication beyond a period of 1 wk. With short-term administration, secobarbital induced a slight decrease in rapid eye movement (REM) and slow-wave sleep and a significant increase in stage 2 sleep. With intermediate administration, sleep stage values were similar to baseline levels. Following withdrawal, there was only a minimal increase in REM sleep above baseline levels, a significant increase in stage 3 sleep, and a significant decrease in stage 2 sleep. The rebound increase in stage 3 sleep is similar to that reported following withdrawal of pentobarbital.", "contents": "Effectiveness of intermediate-term use of secobarbital. Secobarbital, 100 mg, was evaluated in two separate sleep laboratory drug evaluation studies, each with 4 insomniac patients. In both studies, the effect of secobarbital in inducing and maintaining sleep was evaluated, as well as the effects of the drug on sleep stages. Statistical analysis demonstrated that the results of the two studies could be combined. With short-term drug administration of secobarbital (up to 3 nights), there was an improvement in both sleep induction and sleep maintenance. Total wake time was decreased 43% below baseline and was consistently decreased in each third of the night. With intermediate-term drug administration (2 wk), total wake time was decreased only 14% (not statistically significant). Following drug withdrawal, the degree of sleep difficulty returned to baseline levels. The results indicate that secobarbital 100 mg is effective for short-term use but loses much of its effectiveness with intermediate use and suggest that the drug is of limited value for insomniac patients who require nightly medication beyond a period of 1 wk. With short-term administration, secobarbital induced a slight decrease in rapid eye movement (REM) and slow-wave sleep and a significant increase in stage 2 sleep. With intermediate administration, sleep stage values were similar to baseline levels. Following withdrawal, there was only a minimal increase in REM sleep above baseline levels, a significant increase in stage 3 sleep, and a significant decrease in stage 2 sleep. The rebound increase in stage 3 sleep is similar to that reported following withdrawal of pentobarbital."}
{"id": "PMID:185002", "title": "Feline malignant giant cell tumor of bone associated with C-type virus particles.", "content": "A malignant giant cell tumor of bone in a cat is described. Numerous C-type particles were found budding from the neoplastic cells. Viruses have not previously been associated with malignant bone noeplasms in cats.", "contents": "Feline malignant giant cell tumor of bone associated with C-type virus particles. A malignant giant cell tumor of bone in a cat is described. Numerous C-type particles were found budding from the neoplastic cells. Viruses have not previously been associated with malignant bone noeplasms in cats."}
{"id": "PMID:185003", "title": "Serial cyclic transmission of bluetongue virus in sheep and Culicoides variipennis.", "content": "Bluetongue virus (strain 62-45S) was transmitted from sheep to sheep throughout a year by vector bites. A colonized population (SONORA strain, 000 line) of the biological vector Culicoides variipennis (Coquilllett) was used. Fifteen serial cyclic transmissions covered a period of 13 months from October through November of the following year. The mean infection rate of the biting gnats was 37 percent. The clinical response to bluetongue virus was significantly more severe in sheep infected by vector bites than in those inoculated with the virus at the same sheep-serial passage level. A second corroborative serial transmission was conducted for 7 months from June through December. The mean infection rate of the vector was 27%.", "contents": "Serial cyclic transmission of bluetongue virus in sheep and Culicoides variipennis. Bluetongue virus (strain 62-45S) was transmitted from sheep to sheep throughout a year by vector bites. A colonized population (SONORA strain, 000 line) of the biological vector Culicoides variipennis (Coquilllett) was used. Fifteen serial cyclic transmissions covered a period of 13 months from October through November of the following year. The mean infection rate of the biting gnats was 37 percent. The clinical response to bluetongue virus was significantly more severe in sheep infected by vector bites than in those inoculated with the virus at the same sheep-serial passage level. A second corroborative serial transmission was conducted for 7 months from June through December. The mean infection rate of the vector was 27%."}
{"id": "PMID:185004", "title": "Solanum malacoxylon toxicity: inhibition of bone resorption.", "content": "Young rabbits on high (0.57%) or low (0.24%) calcium were given an aqueous extract of Solanum malacoxylon (S.m.) leaves (20 g dried leaves/200 ml distilled water) intragastrically at 0, 12 and 36 hours. On bothe diets S.m. induced progressive hypophosphatasemia but serum calcium and phosphorus underwent only minor changes. In rabbits necropsied at 0, 12, 36, 60, 84 and 108 hours, S.m. was shown to have a negative effect on the resorbing osteocytes. With retarded osteocytic osteolysis, osteopetrosis resulted. Further regressive changes in the osteocytes resulted in osteonecrosis which was observed within 12 hours after administration of S.m. extract. The osteonecrosis, combined with retarded apposition, later resulted in osteopenia. It was concluded that the recommended dietary calcium for growing rabbits--about 0.6%--is too high. Whereas the histologic appearance of bone in rabbits fed low calcium was normal, bones from rabbits on high calcium showed retarded resorption and the rabbits had a relative hypophosphatasemia.", "contents": "Solanum malacoxylon toxicity: inhibition of bone resorption. Young rabbits on high (0.57%) or low (0.24%) calcium were given an aqueous extract of Solanum malacoxylon (S.m.) leaves (20 g dried leaves/200 ml distilled water) intragastrically at 0, 12 and 36 hours. On bothe diets S.m. induced progressive hypophosphatasemia but serum calcium and phosphorus underwent only minor changes. In rabbits necropsied at 0, 12, 36, 60, 84 and 108 hours, S.m. was shown to have a negative effect on the resorbing osteocytes. With retarded osteocytic osteolysis, osteopetrosis resulted. Further regressive changes in the osteocytes resulted in osteonecrosis which was observed within 12 hours after administration of S.m. extract. The osteonecrosis, combined with retarded apposition, later resulted in osteopenia. It was concluded that the recommended dietary calcium for growing rabbits--about 0.6%--is too high. Whereas the histologic appearance of bone in rabbits fed low calcium was normal, bones from rabbits on high calcium showed retarded resorption and the rabbits had a relative hypophosphatasemia."}
{"id": "PMID:185006", "title": "The etiology of inferior vena caval obstruction and compression.", "content": "This review of inferior vena caval obstruction and narrowing centers the discussion on the major groups of diseases which produce primary or secondary obstruction and those which cause distortion or narrowing of the inferior vena cava. Although the majority of these diseases which are involved affect both adults and children, a separate discussion of pediatric causes of inferior vena caval involvement is included. The paper has been organized for discussion by the anatomic areas of potential involvement by disease: the lower, middle, and upper thirds of the vena cava. Other subjects which are covered include a description of the various techniques used for performing inferior vena cavography. A section on the normal anatomy, anatomic variations which may be encountered, and collateral venous pathways is presented. There is also a section on possible pitfalls in interpretation of cavography. The relative value of the vena cavogram in the evaluation of abdominal disease is discussed and the cavogram is compared with other methods of evaluating the retroperitoneum such as arteriography, lymphangiography, excretory urography, and B-mode ultrasonography. Numerous illustrations are included to demonstrate various aspects of inferior vena caval involvement by diseases. Where appropriate, short discussions of the clinical aspects are also included.", "contents": "The etiology of inferior vena caval obstruction and compression. This review of inferior vena caval obstruction and narrowing centers the discussion on the major groups of diseases which produce primary or secondary obstruction and those which cause distortion or narrowing of the inferior vena cava. Although the majority of these diseases which are involved affect both adults and children, a separate discussion of pediatric causes of inferior vena caval involvement is included. The paper has been organized for discussion by the anatomic areas of potential involvement by disease: the lower, middle, and upper thirds of the vena cava. Other subjects which are covered include a description of the various techniques used for performing inferior vena cavography. A section on the normal anatomy, anatomic variations which may be encountered, and collateral venous pathways is presented. There is also a section on possible pitfalls in interpretation of cavography. The relative value of the vena cavogram in the evaluation of abdominal disease is discussed and the cavogram is compared with other methods of evaluating the retroperitoneum such as arteriography, lymphangiography, excretory urography, and B-mode ultrasonography. Numerous illustrations are included to demonstrate various aspects of inferior vena caval involvement by diseases. Where appropriate, short discussions of the clinical aspects are also included."}
{"id": "PMID:185007", "title": "Some specific radiological findings and consideration of linitis plastica of the gastrointestinal tract.", "content": "Linitis plastica denotes a diffuse, intramurally infiltrating, anaplastic carcinoma in a hollow structure resulting in a shrunken organ with thickened walls. Microscopically, linitis plastica is characterized by tumor cells in the presence of inflammatory changes with much fibrosis. Linitis plastica is found most frequently in the stomach where it may produce the classical \"leather-bottle stomach\". Metastases to the colon are frequent via contiguity along mesenteric fascial planes. Therefore, when linitis plastica carcinoma of the stomach or colon is found, the other organ must also be carefully examined. Although rare, primary linitis plastica carcinoma can occur in the colon where it is often characterized by a long stenotic lesion without irritability, sometimes appearing more like an inflammatory lesion than a carcinoma. While the radiological features are not diagnostic, they are, in many cases, suggestive of this entity. The entire spectrum of linitis plastica is reviewed in relationship to the gastrointestinal tract, synthesizing the pertinent literature, with correlation of clinical, pathophysiological, and specific radiological findings.", "contents": "Some specific radiological findings and consideration of linitis plastica of the gastrointestinal tract. Linitis plastica denotes a diffuse, intramurally infiltrating, anaplastic carcinoma in a hollow structure resulting in a shrunken organ with thickened walls. Microscopically, linitis plastica is characterized by tumor cells in the presence of inflammatory changes with much fibrosis. Linitis plastica is found most frequently in the stomach where it may produce the classical \"leather-bottle stomach\". Metastases to the colon are frequent via contiguity along mesenteric fascial planes. Therefore, when linitis plastica carcinoma of the stomach or colon is found, the other organ must also be carefully examined. Although rare, primary linitis plastica carcinoma can occur in the colon where it is often characterized by a long stenotic lesion without irritability, sometimes appearing more like an inflammatory lesion than a carcinoma. While the radiological features are not diagnostic, they are, in many cases, suggestive of this entity. The entire spectrum of linitis plastica is reviewed in relationship to the gastrointestinal tract, synthesizing the pertinent literature, with correlation of clinical, pathophysiological, and specific radiological findings."}
{"id": "PMID:185005", "title": "Analysis of ventilation and performance abnormalities by washout in alveolar air and arterial blood continuous measurement of inert gas.", "content": "The availability of a rapidly responding arterial catheter and gas analyzer permits the observation of inert gas washout from arterial and alveolar sources. These curves are a logical development of alveolar washout techniques and appear to provide significant new information. While a detailed and formal mathematical treatment of combined alveolar, arterial, and mixed venous washout curves has not yet been derived, inspection and measurement of the y-intercept of the terminal slow space has provided considerable understanding into the distribution of V/Q ratios in the critically ill patient.", "contents": "Analysis of ventilation and performance abnormalities by washout in alveolar air and arterial blood continuous measurement of inert gas. The availability of a rapidly responding arterial catheter and gas analyzer permits the observation of inert gas washout from arterial and alveolar sources. These curves are a logical development of alveolar washout techniques and appear to provide significant new information. While a detailed and formal mathematical treatment of combined alveolar, arterial, and mixed venous washout curves has not yet been derived, inspection and measurement of the y-intercept of the terminal slow space has provided considerable understanding into the distribution of V/Q ratios in the critically ill patient."}
{"id": "PMID:185026", "title": "Ultrasonically guided percutaneous biopsy of peripheral pulmonary masses.", "content": "Ultrasonically guided percutaneous biopsy and aspiration of solid and cystic structures in the abdomen, neck, and pericardial space are common practice. The technique may be utilized for biopsy of peripheral pulmonary masses in contact with the chest wall, in order to assure accurate placement of the needle in the center of the mass, reduce the risk of pneumothorax, and eliminate the exposure to radiation that occurs with fluoroscopic guidance. Four patients had successful biopsies in this manner, without complications. Histologic studies revelaed malignant neoplasms in three and lipoid pneumonia in one.", "contents": "Ultrasonically guided percutaneous biopsy of peripheral pulmonary masses. Ultrasonically guided percutaneous biopsy and aspiration of solid and cystic structures in the abdomen, neck, and pericardial space are common practice. The technique may be utilized for biopsy of peripheral pulmonary masses in contact with the chest wall, in order to assure accurate placement of the needle in the center of the mass, reduce the risk of pneumothorax, and eliminate the exposure to radiation that occurs with fluoroscopic guidance. Four patients had successful biopsies in this manner, without complications. Histologic studies revelaed malignant neoplasms in three and lipoid pneumonia in one."}
{"id": "PMID:185027", "title": "Acute appendicitis and postoperative fecal fistula: symptoms of an unrecognized carcinoma of the colon.", "content": "This report is a retrospective evaluation of 12 case histories. All patients had been subjected to laparotomy on suspicion of acute appendicitis. The operative situations seemed to corroborate clinical expectations: an inflamed ileocecal process was assumed to be a result of performation of a gangrenous appendicitis. In three patients a primary adenocarcinoma arising from the appendiceal base was the incidental histologic finding postoperatively. In three other patients this inflammatory-looking process was related to a cecal carcinoma. In six patients a carcinoma existed unrecognized as the basic disease, these patients being subjected to intra-abdominal drainage only or in connection with appendectomy. In five instances a fecal fistula was the main persisting symptom of postoperative morbidity, in one patient even as long as two years after laparotomy. The problem in diagnostic verification of the initially unidentified carcinoma is illustrated. Attention is directed towards avoiding a false feeling of security in the presence of inflammatory manifestations in the right lower abdominal quadrant, which may misleadingly suggest a ruptured appendix.", "contents": "Acute appendicitis and postoperative fecal fistula: symptoms of an unrecognized carcinoma of the colon. This report is a retrospective evaluation of 12 case histories. All patients had been subjected to laparotomy on suspicion of acute appendicitis. The operative situations seemed to corroborate clinical expectations: an inflamed ileocecal process was assumed to be a result of performation of a gangrenous appendicitis. In three patients a primary adenocarcinoma arising from the appendiceal base was the incidental histologic finding postoperatively. In three other patients this inflammatory-looking process was related to a cecal carcinoma. In six patients a carcinoma existed unrecognized as the basic disease, these patients being subjected to intra-abdominal drainage only or in connection with appendectomy. In five instances a fecal fistula was the main persisting symptom of postoperative morbidity, in one patient even as long as two years after laparotomy. The problem in diagnostic verification of the initially unidentified carcinoma is illustrated. Attention is directed towards avoiding a false feeling of security in the presence of inflammatory manifestations in the right lower abdominal quadrant, which may misleadingly suggest a ruptured appendix."}
{"id": "PMID:185028", "title": "Ischemic colitis secondary to Premarin: report of a case.", "content": "A case of reversible ischemic colitis in a young woman taking Premarin, with varium-enema confirmation of the initial diagnosis and subsequent clearing after discontinuation of the oral estrogen preparation, is reported. Ischemic colitis may be more common than realized with the increasing use of conjugated estrogen preparations in menopausal women and elderly men treated for prostatic cancer.", "contents": "Ischemic colitis secondary to Premarin: report of a case. A case of reversible ischemic colitis in a young woman taking Premarin, with varium-enema confirmation of the initial diagnosis and subsequent clearing after discontinuation of the oral estrogen preparation, is reported. Ischemic colitis may be more common than realized with the increasing use of conjugated estrogen preparations in menopausal women and elderly men treated for prostatic cancer."}
{"id": "PMID:185036", "title": "[Xantinol-nicotinate in primary type-V hyperlipoproteinaemia (author's transl)].", "content": "The effect of xantinol-nicotinate (50 mg/kg body-weight) on serum lipids and lipoproteins was tested in 16 out-patients with primary type V hyperlipoproteinaemia. The lipids and lipoproteins were measured before treatment, during a three-week period of drug administration and ten days after it had been stopped. There were no side effects such as flushing or gastritis, and no notable reduction of weight. Each serum-lipid fraction (triglycerides, nonesterified fatty acids, phospholipids, ester-cholesterol and free cholesterol) decreased significantly, regaining the initial values ten days after the drug had been stopped. While chylomicrons and very low-density lipoproteins (VLDL) decreased, there was a significant increase in low-density lipoproteins (LDL). High-density lipoproteins were not significantly changed. The decrease in chylomicrons and the significant decrease in VLDL with xantinol-nicotinate was opposite to that seen with dietary treatment. In none of the patients did LDL increase to abnormally high levels.", "contents": "[Xantinol-nicotinate in primary type-V hyperlipoproteinaemia (author's transl)]. The effect of xantinol-nicotinate (50 mg/kg body-weight) on serum lipids and lipoproteins was tested in 16 out-patients with primary type V hyperlipoproteinaemia. The lipids and lipoproteins were measured before treatment, during a three-week period of drug administration and ten days after it had been stopped. There were no side effects such as flushing or gastritis, and no notable reduction of weight. Each serum-lipid fraction (triglycerides, nonesterified fatty acids, phospholipids, ester-cholesterol and free cholesterol) decreased significantly, regaining the initial values ten days after the drug had been stopped. While chylomicrons and very low-density lipoproteins (VLDL) decreased, there was a significant increase in low-density lipoproteins (LDL). High-density lipoproteins were not significantly changed. The decrease in chylomicrons and the significant decrease in VLDL with xantinol-nicotinate was opposite to that seen with dietary treatment. In none of the patients did LDL increase to abnormally high levels."}
{"id": "PMID:185037", "title": "[Electronmicroscopic characterisation of human plasma lipoproteins after isolation by zonal ultracentrifugation (author's transl)].", "content": "Human plasma proteins were isolated by zonal ultracentrifugation and the fractions obtained examined under the electron microscope. HDL2 had a high degree of uniformity in normal persons, characterised by numerous two-dimensional, hexagonal arrangements. Optical diffraction analysis of HDL2 gave a centre distance of 11.3 nm, individual HDL2 particles being spherical with a diameter of 9.8 nm. HDL3 represented a somewhat less uniform lipoprotein population with a particle diameter between 6.5 and 9.5 nm. LDL had a diameter of 20-25 nm. In patients with hyperlipoproteinaemia type III a third peak was isolated, in addition to the two normal lipoprotein peaks VLDL and LDL. It lies between them and has been called Lp III. VLDL from type III plasma consisted of spherical particles, diameter 31-81 nm, morphologically indistinguishable from normal VLDL. Lp III consisted of a relatively homogeneous spherical lipoprotein population with a diameter of 25-30 nm. LDL consisted of spherical particles whose size was highly homogeneous (18-23 nm diameter), indistinguishable from normal LDL.", "contents": "[Electronmicroscopic characterisation of human plasma lipoproteins after isolation by zonal ultracentrifugation (author's transl)]. Human plasma proteins were isolated by zonal ultracentrifugation and the fractions obtained examined under the electron microscope. HDL2 had a high degree of uniformity in normal persons, characterised by numerous two-dimensional, hexagonal arrangements. Optical diffraction analysis of HDL2 gave a centre distance of 11.3 nm, individual HDL2 particles being spherical with a diameter of 9.8 nm. HDL3 represented a somewhat less uniform lipoprotein population with a particle diameter between 6.5 and 9.5 nm. LDL had a diameter of 20-25 nm. In patients with hyperlipoproteinaemia type III a third peak was isolated, in addition to the two normal lipoprotein peaks VLDL and LDL. It lies between them and has been called Lp III. VLDL from type III plasma consisted of spherical particles, diameter 31-81 nm, morphologically indistinguishable from normal VLDL. Lp III consisted of a relatively homogeneous spherical lipoprotein population with a diameter of 25-30 nm. LDL consisted of spherical particles whose size was highly homogeneous (18-23 nm diameter), indistinguishable from normal LDL."}
{"id": "PMID:185042", "title": "Functional differentiation of the fetal anterior pituitary cells in the rat.", "content": "The onset of hormone synthesis in the rat fetal pituitary gland was studied with the use of the peroxidase labelled antibody method. On the 16th day of fetal life, cells containing immunoreactive ACTH appeared in the primordial cell outgrowth of the Rathke's pouch. In some fetuses, also prolactin cells could be detected at the same developmental stage and these cells were present consistently on subsequent days. Differentiation of ACTH and prolactin cells was followed by onset of TSH, LH and GH synthesis on the 17th, 18th and 19th day of gestation, respectively.", "contents": "Functional differentiation of the fetal anterior pituitary cells in the rat. The onset of hormone synthesis in the rat fetal pituitary gland was studied with the use of the peroxidase labelled antibody method. On the 16th day of fetal life, cells containing immunoreactive ACTH appeared in the primordial cell outgrowth of the Rathke's pouch. In some fetuses, also prolactin cells could be detected at the same developmental stage and these cells were present consistently on subsequent days. Differentiation of ACTH and prolactin cells was followed by onset of TSH, LH and GH synthesis on the 17th, 18th and 19th day of gestation, respectively."}
{"id": "PMID:185043", "title": "Prolactin binding sites in the male rat liver following castration.", "content": "Specific binding sites for prolactin (PRL) have been detected in membrane preparations from the liver of the male rat following castration. The magnitude of the increased binding following castration varied with the age of the animals and with the time after castration. The effect of castration did not appear to be PRL mediated, since increases or decreases of serum PRL levels after pharmacological agents had no effect on PRL binding. The pituitary, however, seems to have a critical role in mediating the increase in PRL binding. Adrenalectomy did not influence the extent of binding of PRL after castration. Testosterone administration, however, completely prevented the increased PRL binding which followed castration. These studies suggest that testosterone has a modulating effect on hepatic PRL binding sites. The maintenance of such binding activity requires not only PRL, but also a functioning pituitary.", "contents": "Prolactin binding sites in the male rat liver following castration. Specific binding sites for prolactin (PRL) have been detected in membrane preparations from the liver of the male rat following castration. The magnitude of the increased binding following castration varied with the age of the animals and with the time after castration. The effect of castration did not appear to be PRL mediated, since increases or decreases of serum PRL levels after pharmacological agents had no effect on PRL binding. The pituitary, however, seems to have a critical role in mediating the increase in PRL binding. Adrenalectomy did not influence the extent of binding of PRL after castration. Testosterone administration, however, completely prevented the increased PRL binding which followed castration. These studies suggest that testosterone has a modulating effect on hepatic PRL binding sites. The maintenance of such binding activity requires not only PRL, but also a functioning pituitary."}
{"id": "PMID:185044", "title": "Characterization of somatogenic and lactogenic binding sites in isolated rat hepatocytes.", "content": "Suspensions of rat hepatocytes isolated enzymatically by the method of Berry and Friend were used to study the binding of 125I-labeled human (hGH) and bovine (bGH) growth hormones and ovine prolactin (oPRL). Displacement of these labeled hormones by their unlabeled analogues was analyzed by means of Scatchard plots and affinity constants (K) and the number of binding sites per cell (q) were calculated. Specificity of binding was studied using hGH, bGH oPRL and rat growth hormone (rGH) and rat prolactin (rPRL). Rat hepatocytes contained two types of binding sites which bound hGH. The first, somatogenic, was specific for the growth-promoting hormones bGH and rGH. The second, lactogenic, was specific for lactogenic hormones, oPRL and rPRL. Human GH, which has both lactogenic and growth-promoting properties in rodents, bound to both sites. The somatogenic binding sites were present in both males and females, and the number of sites was similar in females and in males and was not affected by hypophysectomy. The lactogenic binding sites were present only in females, and the number of lactogenic and somatogenic sites was similar (40,000/cell). The affinity of hGH for the lactogenic binding sites was less than for the somatogenic (0.37 X 10(9) vs. 1 X 10(9)M-1). The lactogenic binding sites were lost when female rats were hypophysectomized and could not be restored by estrogen treatment.", "contents": "Characterization of somatogenic and lactogenic binding sites in isolated rat hepatocytes. Suspensions of rat hepatocytes isolated enzymatically by the method of Berry and Friend were used to study the binding of 125I-labeled human (hGH) and bovine (bGH) growth hormones and ovine prolactin (oPRL). Displacement of these labeled hormones by their unlabeled analogues was analyzed by means of Scatchard plots and affinity constants (K) and the number of binding sites per cell (q) were calculated. Specificity of binding was studied using hGH, bGH oPRL and rat growth hormone (rGH) and rat prolactin (rPRL). Rat hepatocytes contained two types of binding sites which bound hGH. The first, somatogenic, was specific for the growth-promoting hormones bGH and rGH. The second, lactogenic, was specific for lactogenic hormones, oPRL and rPRL. Human GH, which has both lactogenic and growth-promoting properties in rodents, bound to both sites. The somatogenic binding sites were present in both males and females, and the number of sites was similar in females and in males and was not affected by hypophysectomy. The lactogenic binding sites were present only in females, and the number of lactogenic and somatogenic sites was similar (40,000/cell). The affinity of hGH for the lactogenic binding sites was less than for the somatogenic (0.37 X 10(9) vs. 1 X 10(9)M-1). The lactogenic binding sites were lost when female rats were hypophysectomized and could not be restored by estrogen treatment."}
{"id": "PMID:185045", "title": "Acidosis activation of the pituitary-adrenal-renal glutaminase I axis.", "content": "Previous studies have demonstrated that the adrenal glands were necessary for acidosis activation of the mitochondrial glutaminase I pathway. The present studies were undertaken to determine if corticosterone levels are elevated in acidotic rats and if so, whether acidosis stimulates the adrenal glands directly or via the pituitary-adrenal axis. Metabolic acidosis induced by NH4Cl, either acute or chronic, increased corticosterone levels 100 to 130% in intact rats. Acute metabolic acidosis did not activate the mitochondrial pathway in adrenalectomized rats; corticosterone levels were not elevated in hypophysectomized rats nor did activation of the mitochondrial pathway occur in response to acidosis. Therefore, acidosis does not stimulate the adrenal gland directly; rather, it requires the intact pituitary. Administering exogenous corticotropin to hypophysectomized rats resulted in elevation of plasma corticosterone levels and activation of the mitochondrial pathway. The pituitary-adrenal cortex-renal glutaminase I axis apparently operates as a functional unit in the homeostatic response to metabolic acidosis.", "contents": "Acidosis activation of the pituitary-adrenal-renal glutaminase I axis. Previous studies have demonstrated that the adrenal glands were necessary for acidosis activation of the mitochondrial glutaminase I pathway. The present studies were undertaken to determine if corticosterone levels are elevated in acidotic rats and if so, whether acidosis stimulates the adrenal glands directly or via the pituitary-adrenal axis. Metabolic acidosis induced by NH4Cl, either acute or chronic, increased corticosterone levels 100 to 130% in intact rats. Acute metabolic acidosis did not activate the mitochondrial pathway in adrenalectomized rats; corticosterone levels were not elevated in hypophysectomized rats nor did activation of the mitochondrial pathway occur in response to acidosis. Therefore, acidosis does not stimulate the adrenal gland directly; rather, it requires the intact pituitary. Administering exogenous corticotropin to hypophysectomized rats resulted in elevation of plasma corticosterone levels and activation of the mitochondrial pathway. The pituitary-adrenal cortex-renal glutaminase I axis apparently operates as a functional unit in the homeostatic response to metabolic acidosis."}
{"id": "PMID:185046", "title": "In vivo hormonal induction of ornithine decarboxylase in rat kidney.", "content": "Single pharmacological doses of parathyroid hormone, calcitonin, vasopressin, d-aldosterone, or L-triiodothyronine produced a significant increase in the ornithine decarboxylase activity of rat kidney. The activity of kidney ornithine decarboxylase was also enhanced by other hormones, such as pentagastrin and serotonin, which, although they are not known to modify kidney physiology, are secreted by cells having close relationships to the calcitonin-secreting parafollicular cells. The induction of the enzyme was observed in hypophysectomized rats, with or without some other hormone-secreting glands remaining. However, the magnitude of the stimulation elicited by the hormones was somewhat diminished in animals still having the endocrine gland whose hormone was being tested. The maximal stimulation of kidney ornithine decarboxylase activity by parathyroid hormone, calcitonin, vasopressin, L-triiodothyronine, pentagastrin, and serotonin occurred at 4 h after the hormone injection. The enhancement in ornithine decarboxylase activity produced by d-aldosterone was maximal at 3 h after the injection of the hormone. The content of ornithine in the kidney was found to be virtually unchanged whatever the type of hormone treatment. No statistically significant increases in renal ornithine decarboxylase activity of hypophysectomized animals were observed after injection of melatonin or of vitamin D3. Since the stimulating hormones possess clearly different mechanisms of action, the role of cyclic AMP as a general mediator of ornithine decarboxylase induction is questioned.", "contents": "In vivo hormonal induction of ornithine decarboxylase in rat kidney. Single pharmacological doses of parathyroid hormone, calcitonin, vasopressin, d-aldosterone, or L-triiodothyronine produced a significant increase in the ornithine decarboxylase activity of rat kidney. The activity of kidney ornithine decarboxylase was also enhanced by other hormones, such as pentagastrin and serotonin, which, although they are not known to modify kidney physiology, are secreted by cells having close relationships to the calcitonin-secreting parafollicular cells. The induction of the enzyme was observed in hypophysectomized rats, with or without some other hormone-secreting glands remaining. However, the magnitude of the stimulation elicited by the hormones was somewhat diminished in animals still having the endocrine gland whose hormone was being tested. The maximal stimulation of kidney ornithine decarboxylase activity by parathyroid hormone, calcitonin, vasopressin, L-triiodothyronine, pentagastrin, and serotonin occurred at 4 h after the hormone injection. The enhancement in ornithine decarboxylase activity produced by d-aldosterone was maximal at 3 h after the injection of the hormone. The content of ornithine in the kidney was found to be virtually unchanged whatever the type of hormone treatment. No statistically significant increases in renal ornithine decarboxylase activity of hypophysectomized animals were observed after injection of melatonin or of vitamin D3. Since the stimulating hormones possess clearly different mechanisms of action, the role of cyclic AMP as a general mediator of ornithine decarboxylase induction is questioned."}
{"id": "PMID:185047", "title": "Oxytocin-stimulated release of prostaglandin F2alpha from ovine endometrium in vitro: correlation with estrous cycle and oxytocin-receptor binding.", "content": "Endometrial and myometrial tissues, obtained from Merino ewes on 5 different days of the estrous cycle, were incubated at 37 C in 30 ml of gassed (95% O2:5% CO2) Krebs-bicarbonate buffer containing, 0, 10, 100 or 1,000 muU/ml oxytocin. Aliquots of the medium were removed at 10 min intervals and examined for prostaglandin F2alpha (PGF2alpha) content by radioimmunoassay. Fresh-frozen (-70 C) samples of endometrial and myometrial tissue were homogenized in Tyrode's solution. Particulate fractions from each tissue, sedimenting between 1,000 X g for 10 min and 165,000 X g for 30 min, were prepared and assayed for [3H]oxytocin-binding activity. Endometrium incubated in vitro released PGF2alpha spontaneously and oxytocin enhanced this release in a dose-dependent manner. The degree of enhancement with low doses of oxytocin appeared to increase as estrus approached, reaching a maximum on the day of estrus. High-affinity binding sites (Kd = 5 to 7 X 10(-10) M) were found in both myometrium and endometrium. The number of high-affinity sites rose to a peak at estrus in both tissues but the binding capacity of endometrium was twice that of the myometrium at this time. Although both tissues released PGF2alpha during incubation, oxytocin enhanced release from endometrial tissue only. The results suggest that (i) the endometrium is a target for oxytocin, (ii) synthesis of PGF2alpha by the uterus may involve interaction between oxytocin and its endometrial receptors and (iii) ovarian steroids may influence uterine PG synthesis by regulating the availability of these receptors.", "contents": "Oxytocin-stimulated release of prostaglandin F2alpha from ovine endometrium in vitro: correlation with estrous cycle and oxytocin-receptor binding. Endometrial and myometrial tissues, obtained from Merino ewes on 5 different days of the estrous cycle, were incubated at 37 C in 30 ml of gassed (95% O2:5% CO2) Krebs-bicarbonate buffer containing, 0, 10, 100 or 1,000 muU/ml oxytocin. Aliquots of the medium were removed at 10 min intervals and examined for prostaglandin F2alpha (PGF2alpha) content by radioimmunoassay. Fresh-frozen (-70 C) samples of endometrial and myometrial tissue were homogenized in Tyrode's solution. Particulate fractions from each tissue, sedimenting between 1,000 X g for 10 min and 165,000 X g for 30 min, were prepared and assayed for [3H]oxytocin-binding activity. Endometrium incubated in vitro released PGF2alpha spontaneously and oxytocin enhanced this release in a dose-dependent manner. The degree of enhancement with low doses of oxytocin appeared to increase as estrus approached, reaching a maximum on the day of estrus. High-affinity binding sites (Kd = 5 to 7 X 10(-10) M) were found in both myometrium and endometrium. The number of high-affinity sites rose to a peak at estrus in both tissues but the binding capacity of endometrium was twice that of the myometrium at this time. Although both tissues released PGF2alpha during incubation, oxytocin enhanced release from endometrial tissue only. The results suggest that (i) the endometrium is a target for oxytocin, (ii) synthesis of PGF2alpha by the uterus may involve interaction between oxytocin and its endometrial receptors and (iii) ovarian steroids may influence uterine PG synthesis by regulating the availability of these receptors."}
{"id": "PMID:185048", "title": "Potentiation of the ACTH response to metyrapone by L-dopa in the monkey.", "content": "The intravenous injection of L-Dopa (15 mg/kg) to monkeys (Macaca mulatta) failed to alter plasma concentrations of ACTH and of 11-deoxy-cortisol. When cortisol synthesis was blocked with iv metyrapone, potentiation of ACTH secretion by L-Dopa became apparent. Simultaneous injection of L-Dopa and metyrapone resulted in a marked increase in plasma ACTH from 93 +/- 18 pg/ml to 432 +/- 80 pg/ml, whereas plasma 11-deoxycortisol increased from 1.5 +/- 0.2 mug/100 ml to 14.6 +/- 1.0 mug/100 ml 90 min after treatment. Throughout the experiment the rise in ACTH and in 11-deoxycortisol following coadministration of L-Dopa and metyrapone was significantly (P less than 0.01) higher than that produced by metyrapone administration alone. The results suggest that acute administration of L-Dopa in monkeys enhances the response of ACTH to metyrapone. L-Dopa (or one of its metabolites) probably acts upon a noradrenergic or a dopaminergic system located in the hypothalamus to alter the release of hypothalamic corticotropin regulatory factor(s) and thereby enhance the release of ACTH.", "contents": "Potentiation of the ACTH response to metyrapone by L-dopa in the monkey. The intravenous injection of L-Dopa (15 mg/kg) to monkeys (Macaca mulatta) failed to alter plasma concentrations of ACTH and of 11-deoxy-cortisol. When cortisol synthesis was blocked with iv metyrapone, potentiation of ACTH secretion by L-Dopa became apparent. Simultaneous injection of L-Dopa and metyrapone resulted in a marked increase in plasma ACTH from 93 +/- 18 pg/ml to 432 +/- 80 pg/ml, whereas plasma 11-deoxycortisol increased from 1.5 +/- 0.2 mug/100 ml to 14.6 +/- 1.0 mug/100 ml 90 min after treatment. Throughout the experiment the rise in ACTH and in 11-deoxycortisol following coadministration of L-Dopa and metyrapone was significantly (P less than 0.01) higher than that produced by metyrapone administration alone. The results suggest that acute administration of L-Dopa in monkeys enhances the response of ACTH to metyrapone. L-Dopa (or one of its metabolites) probably acts upon a noradrenergic or a dopaminergic system located in the hypothalamus to alter the release of hypothalamic corticotropin regulatory factor(s) and thereby enhance the release of ACTH."}
{"id": "PMID:185049", "title": "Fluorescence polarization measurement of the hormone-binding site interaction.", "content": "Fluorescence polarization methodology has been applied to the binding of fluorescent-labeled prolactin, growth hormone and estradiol to subcellular fractions prepared from rabbit mammary and uterine tissue. Equilibrium measurements treated by Scatchard plots have shown that there are high affinity sites (K approximately 10(9) 1 mol-1), as well as lower affinity sites (K approximately 10(8) 1 mol-1) for both hormones. The binding of the fluorescent labeled hormone to microsomal or cytosol fractions has been shown to be inhibited by the prior addition of native, unlabeled hormone. Kinetic results on the interaction of prolactin with the microsomal fraction are consistent with a bimolecular reaction involving significant structural rearrangements during the reaction (not diffusion controlled). The forward rate constant calculated from data on initial rates was found to be 1.7 X 10(5) 1 mol-1 sec-1. Stopped flow kinetic measurements on the reaction between fluorescent-labeled estradiol and cytosol binding sites show that at low temperatures, the reaction goes in two distinct steps separable in time. The second step may be the reaction found by others (utilizing sedimentation velocity methods) which precedes translocation of the hormone-binding site complex to the nucleus. Fluorescence polarization makes it possible to observe both the formation and dissociation of hormone-binding site complexes over a time scale down to a fraction of a second and at concentrations down to the nanogram per nl range.", "contents": "Fluorescence polarization measurement of the hormone-binding site interaction. Fluorescence polarization methodology has been applied to the binding of fluorescent-labeled prolactin, growth hormone and estradiol to subcellular fractions prepared from rabbit mammary and uterine tissue. Equilibrium measurements treated by Scatchard plots have shown that there are high affinity sites (K approximately 10(9) 1 mol-1), as well as lower affinity sites (K approximately 10(8) 1 mol-1) for both hormones. The binding of the fluorescent labeled hormone to microsomal or cytosol fractions has been shown to be inhibited by the prior addition of native, unlabeled hormone. Kinetic results on the interaction of prolactin with the microsomal fraction are consistent with a bimolecular reaction involving significant structural rearrangements during the reaction (not diffusion controlled). The forward rate constant calculated from data on initial rates was found to be 1.7 X 10(5) 1 mol-1 sec-1. Stopped flow kinetic measurements on the reaction between fluorescent-labeled estradiol and cytosol binding sites show that at low temperatures, the reaction goes in two distinct steps separable in time. The second step may be the reaction found by others (utilizing sedimentation velocity methods) which precedes translocation of the hormone-binding site complex to the nucleus. Fluorescence polarization makes it possible to observe both the formation and dissociation of hormone-binding site complexes over a time scale down to a fraction of a second and at concentrations down to the nanogram per nl range."}
{"id": "PMID:185050", "title": "Biosynthesis of adrenodoxin in mouse adrenal tumor cells.", "content": "ACTH and cAMP stimulate steroidogenesis and the mitochondrial electron transport system for steroid hydroxylation in cultured mouse adrenal cortex tumor cells. During this stimulation, the biosynthesis of adrenodoxin, a non-heme iron protein which is one of the electron transport enzymes, was examined. 14C-labeled adrenodoxin was isolated by employing a purified rabbit antibody to bovine adrenodoxin. The antibody-adrenodoxin precipitates were further purified by acrylamide gel electrophoresis. It was observed that the biosynthesis of adrenodoxin was stimulated in response to ACTH induction and that this stimulation was completely inhibited with cycloheximide and partially inhibited with chloramphenicol. As a result, it was concluded that adrenodoxin requires both mitochondrial and cytosol ribosomal activities for its synthesis and integration into adrenal mitochondria.", "contents": "Biosynthesis of adrenodoxin in mouse adrenal tumor cells. ACTH and cAMP stimulate steroidogenesis and the mitochondrial electron transport system for steroid hydroxylation in cultured mouse adrenal cortex tumor cells. During this stimulation, the biosynthesis of adrenodoxin, a non-heme iron protein which is one of the electron transport enzymes, was examined. 14C-labeled adrenodoxin was isolated by employing a purified rabbit antibody to bovine adrenodoxin. The antibody-adrenodoxin precipitates were further purified by acrylamide gel electrophoresis. It was observed that the biosynthesis of adrenodoxin was stimulated in response to ACTH induction and that this stimulation was completely inhibited with cycloheximide and partially inhibited with chloramphenicol. As a result, it was concluded that adrenodoxin requires both mitochondrial and cytosol ribosomal activities for its synthesis and integration into adrenal mitochondria."}
{"id": "PMID:185051", "title": "Diglyceride kinase activity of microtubules. Characterization and comparison with the protein kinase and ATPase activities associated with vinblastine-isolated tubulin of chick embryonic muscles.", "content": "Vinblastine-isolated microtubule protein from chick embryonic muscles has an enzymatic activity which catalyzes the formation of phosphatidic acid from diglycerides and ATP. The pH optimum (6.4), sedimentation on sucrose gradients (Mr = 85 000), and sensitivity to ions of this diglyceride kinase activity are different to those of a similar enzymatic activity present in 150 000 X g supernatants of chick embryonic muscle homogenates, suggesting that it is a different species which is associated specifically with the microtubules. The reaction requires a divalent ion (e.g. 0.4 mM Mg2+ gives half-maximal stimulation), and GTP can replace ATP rather effectively, especially at nucleotide concentrations lower than 50 muM. The sedimentation of the diglyceride kinase on sucrose gradients coincides with that of the microtubules-associated protein kinase (Mr = 75 000); the heat-stability and sensivitity to proteolysis of both activities are also very similar. Stimulation of one reaction by the addition of the corresponding exogenous substrate does not impair the phosphorylation of the other, and no radioactivity is lost from phosphatidic acid or the protein moiety upon incubation of pre-labelled microtubules with a large excess of unlabelled ATP or GTP. In addition to diglyceride and protein kinase activities (0.2 and 0.3 nmol 32P-transferred X min-1 X mg-1 microtubular protein, respectively), microtubules also contain an associated ATPase (2.8 nmol X min-1 X mg-1), which requires either Mg2+ or Ca2+, can hydrolyze GTP quite effectively, and sediments with a molecular weight of 95000. The results obtained are discussed in connection with the possible relationships existing among these enzymatic activities, as well as their probable role in microtubular functions.", "contents": "Diglyceride kinase activity of microtubules. Characterization and comparison with the protein kinase and ATPase activities associated with vinblastine-isolated tubulin of chick embryonic muscles. Vinblastine-isolated microtubule protein from chick embryonic muscles has an enzymatic activity which catalyzes the formation of phosphatidic acid from diglycerides and ATP. The pH optimum (6.4), sedimentation on sucrose gradients (Mr = 85 000), and sensitivity to ions of this diglyceride kinase activity are different to those of a similar enzymatic activity present in 150 000 X g supernatants of chick embryonic muscle homogenates, suggesting that it is a different species which is associated specifically with the microtubules. The reaction requires a divalent ion (e.g. 0.4 mM Mg2+ gives half-maximal stimulation), and GTP can replace ATP rather effectively, especially at nucleotide concentrations lower than 50 muM. The sedimentation of the diglyceride kinase on sucrose gradients coincides with that of the microtubules-associated protein kinase (Mr = 75 000); the heat-stability and sensivitity to proteolysis of both activities are also very similar. Stimulation of one reaction by the addition of the corresponding exogenous substrate does not impair the phosphorylation of the other, and no radioactivity is lost from phosphatidic acid or the protein moiety upon incubation of pre-labelled microtubules with a large excess of unlabelled ATP or GTP. In addition to diglyceride and protein kinase activities (0.2 and 0.3 nmol 32P-transferred X min-1 X mg-1 microtubular protein, respectively), microtubules also contain an associated ATPase (2.8 nmol X min-1 X mg-1), which requires either Mg2+ or Ca2+, can hydrolyze GTP quite effectively, and sediments with a molecular weight of 95000. The results obtained are discussed in connection with the possible relationships existing among these enzymatic activities, as well as their probable role in microtubular functions."}
{"id": "PMID:185052", "title": "The importance of arginine residues in the catalytic and regulatory functions of bovine-liver glutamate dehydrogenase.", "content": "Bovine liver glutamate dehydrogenase reacts rapidly with 2,3-butanedione to yield modified enzyme with 29% of its original maximum activity, but no change in its Michaelis constants for substrates and coenzymes. No significant reduction in the inactivation rate is produced by the addition of the allosteric activator ADP or inhibitor GTP, while partial protection against inactivation is provided by the coenzyme NAD+ or substrate 2-oxoglutarate when added separately. The most marked decrease in the rate of inactivation (about 10-fold) is provided by the combined addition of NAD+ and 2-oxoglutarate, suggesting that modification takes place in the region of the active site. Reaction with 2,3-butanedione also results in loss of the ability of the enzyme to be activated by ADP. Addition of ADP (but not NAD+, 2-oxoglutarate or GTP) to the incubation mixture protects markedly against the loss of activatability of ADP. It is concluded that 2,3-butanedione produces two distinguishable effects on glutamate dehydrogenase: a relatively specific modification of the regulatory ADP site and a distinct modification in the active center. Reaction of two arginyl residues per peptide chain appears to be responsible for disruption of the ADP activation property of the enzyme, while alteration of a maximum of five arginyl residues can be related to the reduction of maximum catalytic activity. Electrostatic interactions between the positively charged arginine groups and the negatively charged substrate, coenzyme and allosteric purine nucleotide may be important for the normal function of glutamate dehydrogenase.", "contents": "The importance of arginine residues in the catalytic and regulatory functions of bovine-liver glutamate dehydrogenase. Bovine liver glutamate dehydrogenase reacts rapidly with 2,3-butanedione to yield modified enzyme with 29% of its original maximum activity, but no change in its Michaelis constants for substrates and coenzymes. No significant reduction in the inactivation rate is produced by the addition of the allosteric activator ADP or inhibitor GTP, while partial protection against inactivation is provided by the coenzyme NAD+ or substrate 2-oxoglutarate when added separately. The most marked decrease in the rate of inactivation (about 10-fold) is provided by the combined addition of NAD+ and 2-oxoglutarate, suggesting that modification takes place in the region of the active site. Reaction with 2,3-butanedione also results in loss of the ability of the enzyme to be activated by ADP. Addition of ADP (but not NAD+, 2-oxoglutarate or GTP) to the incubation mixture protects markedly against the loss of activatability of ADP. It is concluded that 2,3-butanedione produces two distinguishable effects on glutamate dehydrogenase: a relatively specific modification of the regulatory ADP site and a distinct modification in the active center. Reaction of two arginyl residues per peptide chain appears to be responsible for disruption of the ADP activation property of the enzyme, while alteration of a maximum of five arginyl residues can be related to the reduction of maximum catalytic activity. Electrostatic interactions between the positively charged arginine groups and the negatively charged substrate, coenzyme and allosteric purine nucleotide may be important for the normal function of glutamate dehydrogenase."}
{"id": "PMID:185053", "title": "An approach to the antigenic structure of arginine kinase and creatine kinase. Physical, chemical and immunological study of some modified derivatives.", "content": "The antigenic structure of arginine kinase and creatine kinase has been approached using chemical modifications and enzymatic cleavage. Mild performic oxidation that, with a restricted number of oxidized amino acid residues, results for both enzymes in a severe decrease of the helical structure and in a large increase of the protein-solvent interactions, affects differently their antigenic reactivity: when compared with antisera to the homologous native enzymes, arginine kinase and its oxidized derivative cross-react fully, while creatine kinase and its oxidized derivative cross-react only about 30%. The persistence of the antigenic reactivity of arginine kinase through drastic structural alterations is confirmed by the high inhibitory capacity (about 80%) of crude tryptic hydrolyzates towards the combination of argining kinase with its specific antibodies. Tryptic peptides of creatine kinase, obtained in the same conditions, inhibit weakly (about 12%) the homologous antigen-antibody interaction. The participation of the lysines in the antigenicity of arginine kinase and creatine kinase is suggested by the enhanced inhibitory capacity of the tryptic hydrolyzates when the cleavage is restricted to the arginyl peptide bounds, and was verified for arginine kinase through assays with lysine-modified derivatives.", "contents": "An approach to the antigenic structure of arginine kinase and creatine kinase. Physical, chemical and immunological study of some modified derivatives. The antigenic structure of arginine kinase and creatine kinase has been approached using chemical modifications and enzymatic cleavage. Mild performic oxidation that, with a restricted number of oxidized amino acid residues, results for both enzymes in a severe decrease of the helical structure and in a large increase of the protein-solvent interactions, affects differently their antigenic reactivity: when compared with antisera to the homologous native enzymes, arginine kinase and its oxidized derivative cross-react fully, while creatine kinase and its oxidized derivative cross-react only about 30%. The persistence of the antigenic reactivity of arginine kinase through drastic structural alterations is confirmed by the high inhibitory capacity (about 80%) of crude tryptic hydrolyzates towards the combination of argining kinase with its specific antibodies. Tryptic peptides of creatine kinase, obtained in the same conditions, inhibit weakly (about 12%) the homologous antigen-antibody interaction. The participation of the lysines in the antigenicity of arginine kinase and creatine kinase is suggested by the enhanced inhibitory capacity of the tryptic hydrolyzates when the cleavage is restricted to the arginyl peptide bounds, and was verified for arginine kinase through assays with lysine-modified derivatives."}
{"id": "PMID:185054", "title": "New methods for the study of complex enzyme kinetics illustrated by analysis of the wavy curves of v versus (S) and non-linear double-reciprocal plots for human-placental 15-hydroxyprostaglandin dehydrogenase.", "content": "A new method for discovering the minimum degree of rate equations using only the experimental graphs and a straight-edge (transparent ruler) is presented. This method is then illustrated by an analysis of the wavy v vs [S] curves and non-linear double-reciprocal plots reproducibly given by NAD-dependent 15-hydroxyprostaglandin dehydrogenase for which a new improved purification is described. It is shown by this analysis that the enzyme has a complex mechanism involving cooperatively linked dependent sites and requiring a rate equation of at least fourth degree in prostaglandin and NAD+ with no kinetically significant dead-end complexes.", "contents": "New methods for the study of complex enzyme kinetics illustrated by analysis of the wavy curves of v versus (S) and non-linear double-reciprocal plots for human-placental 15-hydroxyprostaglandin dehydrogenase. A new method for discovering the minimum degree of rate equations using only the experimental graphs and a straight-edge (transparent ruler) is presented. This method is then illustrated by an analysis of the wavy v vs [S] curves and non-linear double-reciprocal plots reproducibly given by NAD-dependent 15-hydroxyprostaglandin dehydrogenase for which a new improved purification is described. It is shown by this analysis that the enzyme has a complex mechanism involving cooperatively linked dependent sites and requiring a rate equation of at least fourth degree in prostaglandin and NAD+ with no kinetically significant dead-end complexes."}
{"id": "PMID:185056", "title": "Kinetics of insulin secretion in chronic pancreatitis and mild maturity onset diabetes. (Evidence for \"gut hormone\" action beyond glucoreceptor and cyclic adenosine monophosphate mediated insulin release).", "content": "We studied insulin responses to glucose with and without cholecystokinin-pancreozymin and aminophyllin infusions in normal, chronic pancreatitic and genetic (maturity-onset) diabetic subjects. Glucose was given alone as separate 5 and 10 g boluses followed by infusion at 250 mg/min. and 500 mg/min., respectively. Chronic pancreatitis patients and genetic diabetic patients had decreased Imax values, indicating a decreased insulin reserve. Sensitivity to glucose was normal in pancreatitic subjects, but the diabetic subjects had a raised G50 value, compatible with glucoreceptor dysfunction. Infusions of aminophyllin enhanced insulin responses (Imax) to glucose injection in normal subjects and to a lesser degree in pancreatitic subjects, but decreased sensitivity to glucose (increase in G50) in both groups. Although the Imax value in pancreatitic subjects was significantly lower than in the control subjects during the glucose plus aminophyllin infusion, the blood glucose concentration in the pancreatitic subjects was nonetheless decreased. This suggests that pancreatitic subjects have increased endogenous insulin sensitivity. Aminophyllin had no effect in diabetic subjects. Crude cholecystokinin-pancreozymin changed the shape of the glucose/insulin dose response curve in normal, pancreatitic and diabetic subjects. These findings further suggest that the defect in insulin secretion in pancreatitic subjects is partly situated at the cyclic adenosine monophosphate stage of insulin release. Crude cholecystokin-pancreozymin seems to affect insulin release at a point beyond the cyclic adenosine monophosphate stage.", "contents": "Kinetics of insulin secretion in chronic pancreatitis and mild maturity onset diabetes. (Evidence for \"gut hormone\" action beyond glucoreceptor and cyclic adenosine monophosphate mediated insulin release). We studied insulin responses to glucose with and without cholecystokinin-pancreozymin and aminophyllin infusions in normal, chronic pancreatitic and genetic (maturity-onset) diabetic subjects. Glucose was given alone as separate 5 and 10 g boluses followed by infusion at 250 mg/min. and 500 mg/min., respectively. Chronic pancreatitis patients and genetic diabetic patients had decreased Imax values, indicating a decreased insulin reserve. Sensitivity to glucose was normal in pancreatitic subjects, but the diabetic subjects had a raised G50 value, compatible with glucoreceptor dysfunction. Infusions of aminophyllin enhanced insulin responses (Imax) to glucose injection in normal subjects and to a lesser degree in pancreatitic subjects, but decreased sensitivity to glucose (increase in G50) in both groups. Although the Imax value in pancreatitic subjects was significantly lower than in the control subjects during the glucose plus aminophyllin infusion, the blood glucose concentration in the pancreatitic subjects was nonetheless decreased. This suggests that pancreatitic subjects have increased endogenous insulin sensitivity. Aminophyllin had no effect in diabetic subjects. Crude cholecystokinin-pancreozymin changed the shape of the glucose/insulin dose response curve in normal, pancreatitic and diabetic subjects. These findings further suggest that the defect in insulin secretion in pancreatitic subjects is partly situated at the cyclic adenosine monophosphate stage of insulin release. Crude cholecystokin-pancreozymin seems to affect insulin release at a point beyond the cyclic adenosine monophosphate stage."}
{"id": "PMID:185057", "title": "Primary and secondary in vitro generation of cytolytic T lymphocytes in the murine sarcoma virus system.", "content": "Cell-mediated cytotoxic responses in vitro to surface antigens associated with murine sarcoma virus (MSV)-induced tumors were investigated using mixed leukocyte-tumor cell cultures (MLTC). The source of responding cells was either spleens from normal C57BL/6 mice (primary MLTC) or spleens of C57BL/6 mice carrying or having rejected a MSV-induced tumor (secondary MLTC). Graffi virus-induced GiL-4 leukemia cells, Rauscher virus-induced RB1-5 leukemia cells, and MSV-induced MSV-B16 sarcoma cells were used as stimulating syngeneic tumor cells and/or target cells. Under appropriate culture conditions, cytolytic T lymphocytes (CTL) were generated in both primary and secondary MLTC. As assessed by a quantitative short-term 51Cr release assay system, CTL activity in secondary MLTC populations was at least 10-fold higher than that in primary MLTC populations, and 100-fold higher than that in spleen cells taken at the peak of the in vivo response of MSV-infected mice. The ability of spleen cells to mount a secondary CTL response in vitro could be observed as early as 5 days after virus injection, increased up to the time of maximum tumor size and persisted long after tumor regression. This suggests the development of increased numbers of CTL progenitors and/or the formation of \"memory\" CTL in spleens of MSV-injected mice.", "contents": "Primary and secondary in vitro generation of cytolytic T lymphocytes in the murine sarcoma virus system. Cell-mediated cytotoxic responses in vitro to surface antigens associated with murine sarcoma virus (MSV)-induced tumors were investigated using mixed leukocyte-tumor cell cultures (MLTC). The source of responding cells was either spleens from normal C57BL/6 mice (primary MLTC) or spleens of C57BL/6 mice carrying or having rejected a MSV-induced tumor (secondary MLTC). Graffi virus-induced GiL-4 leukemia cells, Rauscher virus-induced RB1-5 leukemia cells, and MSV-induced MSV-B16 sarcoma cells were used as stimulating syngeneic tumor cells and/or target cells. Under appropriate culture conditions, cytolytic T lymphocytes (CTL) were generated in both primary and secondary MLTC. As assessed by a quantitative short-term 51Cr release assay system, CTL activity in secondary MLTC populations was at least 10-fold higher than that in primary MLTC populations, and 100-fold higher than that in spleen cells taken at the peak of the in vivo response of MSV-infected mice. The ability of spleen cells to mount a secondary CTL response in vitro could be observed as early as 5 days after virus injection, increased up to the time of maximum tumor size and persisted long after tumor regression. This suggests the development of increased numbers of CTL progenitors and/or the formation of \"memory\" CTL in spleens of MSV-injected mice."}
{"id": "PMID:185058", "title": "Studies on the effect of various agents on the maturation of thymus stem cells.", "content": "Experiments were carried out on 14-day fetal mouse thymic stem cells which were treated with agents known to increase cellular cAMP levels for a period of 90 min at 37 degrees C. When compared to controls, a high proportion of treated stem cells were found to develop Thy-1 (theta) antigen as indicated by dye exclusion tests using anti-Thy-1 serum and complement.", "contents": "Studies on the effect of various agents on the maturation of thymus stem cells. Experiments were carried out on 14-day fetal mouse thymic stem cells which were treated with agents known to increase cellular cAMP levels for a period of 90 min at 37 degrees C. When compared to controls, a high proportion of treated stem cells were found to develop Thy-1 (theta) antigen as indicated by dye exclusion tests using anti-Thy-1 serum and complement."}
{"id": "PMID:185059", "title": "Analysis of human thymocyte subpopulations using discontinuous gradients of albumin: precursor lymphocytes in human thymus.", "content": "Precursor lymphocytes, obtained from human tissue on bovine serum albumin (BSA) gradients followed by removal of sheep erythrocyte (E)-reactive thymocytes on Ficoll, are the predominant lymphoid subpopulation found in young fetal thymuses. This subpopulation shows a progressive decline in relative numbers during fetal life, accompanied by a rise in both the relative and absolute numbers of E-reactive thymocytes. Precursor thymocytes differentiate in vitro to E-reactive cells resembling T cells in their morphology, sedimentation on BSA gradients, and response to phytohemagglutinin. Agents tending to increase intracellular concentrations of cyclic-AMP accelerate the rate of differentiation of precursor cells to lymphocytes which closely resemble T cells.", "contents": "Analysis of human thymocyte subpopulations using discontinuous gradients of albumin: precursor lymphocytes in human thymus. Precursor lymphocytes, obtained from human tissue on bovine serum albumin (BSA) gradients followed by removal of sheep erythrocyte (E)-reactive thymocytes on Ficoll, are the predominant lymphoid subpopulation found in young fetal thymuses. This subpopulation shows a progressive decline in relative numbers during fetal life, accompanied by a rise in both the relative and absolute numbers of E-reactive thymocytes. Precursor thymocytes differentiate in vitro to E-reactive cells resembling T cells in their morphology, sedimentation on BSA gradients, and response to phytohemagglutinin. Agents tending to increase intracellular concentrations of cyclic-AMP accelerate the rate of differentiation of precursor cells to lymphocytes which closely resemble T cells."}
{"id": "PMID:185060", "title": "Receptors for immune complexes on cells within a polyoma virus-induced murine sarcoma.", "content": "Cells present in the polyoma virus-induced murine ascites tumor SEYF-a showed the capacity to fix soluble immune complexes of ovalbumin anti-ovalbumin. The fixation could be inhibited by preincubating the cells with antisera directed against H-2 antigens and with syngeneic anti-tumor antibodies. The latter did not react with normal cells. Depletion of phagocytes from the ascites cell population, thus enriching for tumor cells, increased the inhibition of complex fixation by the syngeneic anti-tumor antiserum. The inhibition of complex fixation by the anti-tumor antibodies was not mediated by \"third-party\" complexes. Pepsin-treated globulin derived from the syngeneic anti-tumor antiserum could still inhibit complex fixation by SEYF-a cells. These results raise the possibility that tumor cells, per se, expressed receptors for immune complexes. Macrophages, apparently of host origin, residing in the SEYF-a tumor, also expressed such receptors.", "contents": "Receptors for immune complexes on cells within a polyoma virus-induced murine sarcoma. Cells present in the polyoma virus-induced murine ascites tumor SEYF-a showed the capacity to fix soluble immune complexes of ovalbumin anti-ovalbumin. The fixation could be inhibited by preincubating the cells with antisera directed against H-2 antigens and with syngeneic anti-tumor antibodies. The latter did not react with normal cells. Depletion of phagocytes from the ascites cell population, thus enriching for tumor cells, increased the inhibition of complex fixation by the syngeneic anti-tumor antiserum. The inhibition of complex fixation by the anti-tumor antibodies was not mediated by \"third-party\" complexes. Pepsin-treated globulin derived from the syngeneic anti-tumor antiserum could still inhibit complex fixation by SEYF-a cells. These results raise the possibility that tumor cells, per se, expressed receptors for immune complexes. Macrophages, apparently of host origin, residing in the SEYF-a tumor, also expressed such receptors."}
{"id": "PMID:185061", "title": "Naltrexone-induced hypothermia in the rat.", "content": "Naltrexone, in relatively high doses, has been reported to cause a fall in body temperature in human ex-heroin addicts who had been abstinent for at least 6 weeks. The underlying mechanism of this hypothermic effect has been investigated in rats. The first consideration was that the temperature change was a reflection of delayed withdrawal but rats implanted with a morphine pellet 45 days earlier showed no significant change in temperature after a dose of naltrexone that caused marked withdrawal hypothermia in dependent rats implanted 3 days previously. A fall in core temperature was only induced in rats after doses of 80 and 160 mg/kg i.p. of naltrexone. Behavioral thermoregulatory studies revealed that the animals correct the falling body temperature by increased exposure to a radiant heat source indicating that the central thermostats had not been significantly affected by the drug. These data suggest that the major component in the hypothermic effect of naltrexone is activation of efferent heat loss pathways or peripheral heat loss mechanisms. Due to current suggestions that opiate receptors might represent the receptors for an endogenous transmitter the results are discussed in relation to this consideration. When compared to the sites and mechanism of action of opiates on thermoregulation the results with naltrexone lend little support to the hypothesis that the fall in temperature is due to displacement of an endogenous substance from central opiate receptors.", "contents": "Naltrexone-induced hypothermia in the rat. Naltrexone, in relatively high doses, has been reported to cause a fall in body temperature in human ex-heroin addicts who had been abstinent for at least 6 weeks. The underlying mechanism of this hypothermic effect has been investigated in rats. The first consideration was that the temperature change was a reflection of delayed withdrawal but rats implanted with a morphine pellet 45 days earlier showed no significant change in temperature after a dose of naltrexone that caused marked withdrawal hypothermia in dependent rats implanted 3 days previously. A fall in core temperature was only induced in rats after doses of 80 and 160 mg/kg i.p. of naltrexone. Behavioral thermoregulatory studies revealed that the animals correct the falling body temperature by increased exposure to a radiant heat source indicating that the central thermostats had not been significantly affected by the drug. These data suggest that the major component in the hypothermic effect of naltrexone is activation of efferent heat loss pathways or peripheral heat loss mechanisms. Due to current suggestions that opiate receptors might represent the receptors for an endogenous transmitter the results are discussed in relation to this consideration. When compared to the sites and mechanism of action of opiates on thermoregulation the results with naltrexone lend little support to the hypothesis that the fall in temperature is due to displacement of an endogenous substance from central opiate receptors."}
{"id": "PMID:185062", "title": "Pharmacological evidence for a stimulation of dopamine neurons by noradrenaline neurons in the brain.", "content": "The effects of yohimbine (3 mg/kg i.p.), phenoxybenzamine (20 mg/kg i.p.) and clonidine (0.1 mg/kg i.p.) on the synthesis and the utilization of dopamine and noradrenaline in the central nervous system of rats were investigated. Dopa accumulation following decarboxylase inhibition and the alpha-methyltyrosine-induced disappearance of the amines were used as the measure of these effects. The synthesis and the utilization of dopamine and noradrenaline were accelerated by yohimbine. Clonidine plus phenoxybenzamine inhibited the synthesis and utilization of dopamine and the combination also partly antagonized the effects of yohimbine on the trunover of dopamine. The effects of the three drugs on the synthesis and utilization of dopamine might be secondary to their actions on alpha-adrenoreceptors of noradrenaline synapses since, at the doses used, yohimbine increases the release of noradrenaline, phenoxybenzamine blocks postsynapptic noradrenaline receptors and clonidine reduces the release of noradrenaline. This hypothesis is supported by the findings that yohimbine and phenoxybenzamine did not change the increased synthesis of dopamine in reserpine-treated rats and that clonidine did not inhibit the increased synthesis of dopamine after axotomy or treatment with reserpine.", "contents": "Pharmacological evidence for a stimulation of dopamine neurons by noradrenaline neurons in the brain. The effects of yohimbine (3 mg/kg i.p.), phenoxybenzamine (20 mg/kg i.p.) and clonidine (0.1 mg/kg i.p.) on the synthesis and the utilization of dopamine and noradrenaline in the central nervous system of rats were investigated. Dopa accumulation following decarboxylase inhibition and the alpha-methyltyrosine-induced disappearance of the amines were used as the measure of these effects. The synthesis and the utilization of dopamine and noradrenaline were accelerated by yohimbine. Clonidine plus phenoxybenzamine inhibited the synthesis and utilization of dopamine and the combination also partly antagonized the effects of yohimbine on the trunover of dopamine. The effects of the three drugs on the synthesis and utilization of dopamine might be secondary to their actions on alpha-adrenoreceptors of noradrenaline synapses since, at the doses used, yohimbine increases the release of noradrenaline, phenoxybenzamine blocks postsynapptic noradrenaline receptors and clonidine reduces the release of noradrenaline. This hypothesis is supported by the findings that yohimbine and phenoxybenzamine did not change the increased synthesis of dopamine in reserpine-treated rats and that clonidine did not inhibit the increased synthesis of dopamine after axotomy or treatment with reserpine."}
{"id": "PMID:185063", "title": "Effect of decentralization and glucose withdrawal on the potassium-induced cAMP increase in the rabbit superior cervical ganglion.", "content": "The concentration of cAMP in the isolated rabbit superior cervical ganglion (SCG) increases when the tissue is exposed to high potassium media for short periods. The increase was found not to be affected by agents that are known to potentiate or to antagonize the postsynaptic effects of acetylcholine. Pretreatment of the rabbits with various sympaticolytic substances did not appear to affect the cAMP increase in the isolated SCG. It was found that the K+-induced cAMP synthesis occurred neither in ganglia which had been decentralized 3 days before isolation nor in intact ganglia preincubated in a glucose-free medium. Under both these conditions the effect of potassium declines with a time course which is characteristic for the degeneration of the presynaptic terminals. These terminals therefore, appear to be the most likely site for the cAMP increase.", "contents": "Effect of decentralization and glucose withdrawal on the potassium-induced cAMP increase in the rabbit superior cervical ganglion. The concentration of cAMP in the isolated rabbit superior cervical ganglion (SCG) increases when the tissue is exposed to high potassium media for short periods. The increase was found not to be affected by agents that are known to potentiate or to antagonize the postsynaptic effects of acetylcholine. Pretreatment of the rabbits with various sympaticolytic substances did not appear to affect the cAMP increase in the isolated SCG. It was found that the K+-induced cAMP synthesis occurred neither in ganglia which had been decentralized 3 days before isolation nor in intact ganglia preincubated in a glucose-free medium. Under both these conditions the effect of potassium declines with a time course which is characteristic for the degeneration of the presynaptic terminals. These terminals therefore, appear to be the most likely site for the cAMP increase."}
{"id": "PMID:185064", "title": "Block of electrically induced contractions of guinea pig longitudinal muscle by prostaglandin synthetase and receptor inhibitors.", "content": "Inhibitors of prostaglandin synthetase as well as prostaglandin receptor inhibitors block electrically induced contractions of the longitudinal muscle of the guinea pig ileum. This blockade is selectivety reversed by some prostaglandins, particularly those of the E series. There is a very close parallel between the potency with which the synthetase inhabitors block transmission and inhibit the enzyme. That blockade is actually accompanied by inhibition of synthesis of PG was shown by inhibition of arachidonic acid contractions of the tissue by indomethacin. The inhibition of transmission by indomethacin involves block of acetylcholine release as shown by direct assay and by the fact that physostigmine can reverse the block. Physostigmine also reverses block of transmission by prostaglandin receptor inhibitors and by morphine but not that produced by chlorpromazine or papaverine. Other evidence for a presynaptic site of action for the synthetase and PG receptor inhibitors is indicated by lack of effect of blocking concentrations on response of the tissue to exogenous acetylcholine. That prostaglandin reverses block of transmission by a presynaptic effect was shown by lack of reversal of atropine and papaverine inhibition of electrically induced contractions; both of these drugs produce this effect directly on the smooth muscle. These results are compatible with the previous postulate that a prostaglandin system, comprised of prostaglandin, its synthesizing enzyme and its receptor, is directly involved with the release of acetylcholine in the ileum.", "contents": "Block of electrically induced contractions of guinea pig longitudinal muscle by prostaglandin synthetase and receptor inhibitors. Inhibitors of prostaglandin synthetase as well as prostaglandin receptor inhibitors block electrically induced contractions of the longitudinal muscle of the guinea pig ileum. This blockade is selectivety reversed by some prostaglandins, particularly those of the E series. There is a very close parallel between the potency with which the synthetase inhabitors block transmission and inhibit the enzyme. That blockade is actually accompanied by inhibition of synthesis of PG was shown by inhibition of arachidonic acid contractions of the tissue by indomethacin. The inhibition of transmission by indomethacin involves block of acetylcholine release as shown by direct assay and by the fact that physostigmine can reverse the block. Physostigmine also reverses block of transmission by prostaglandin receptor inhibitors and by morphine but not that produced by chlorpromazine or papaverine. Other evidence for a presynaptic site of action for the synthetase and PG receptor inhibitors is indicated by lack of effect of blocking concentrations on response of the tissue to exogenous acetylcholine. That prostaglandin reverses block of transmission by a presynaptic effect was shown by lack of reversal of atropine and papaverine inhibition of electrically induced contractions; both of these drugs produce this effect directly on the smooth muscle. These results are compatible with the previous postulate that a prostaglandin system, comprised of prostaglandin, its synthesizing enzyme and its receptor, is directly involved with the release of acetylcholine in the ileum."}
{"id": "PMID:185065", "title": "Adenosine 3',5'-cyclic monophosphate as a possible mediator of rotational behaviour induced by dopaminergic receptor stimulation in rats lesioned unilaterally in the substantia nigra.", "content": "A possible involvement of c-AMP in the rotational behaviour induced by a stimulation of dopamine receptors in corpus striatum of rats was investigated. Rats were lesioned unilaterally in the substantia nigra with 6-hydroxydopamine. Intraventricular injection of dopamine, norepinephrine and apomorphine induced rotational behaviour towards the intact side as did dibutyryl c-AMP (dB-c-AMP). Dopamine, norepinephrine and apomorphine could activate adenylate cyclase in homogenates of caudate nucleus. The activation by dopamine was blocked by haloperidol. I.p. injected apomorphine increased c-AMP content bilaterally in caudate nucleus and caused turning towards the intact side; theophylline potentiated and haloperidol blocked the effect. In non-lesioned rats, dopamine and norepinephrine, when injected unilaterally into the caudate nucleus, elicited truning twoards the non-injected side if the rats were pretreated with reserpine and tranylcypromine. c-AMP and dB-c-AMP given similarly to rats pretreated with theophylline also produced turning towards the non-injected side regardless the pretreatment with reserpine and tranylcypromine. All these results emphasize the possibility that c-AMP acts as a second messenger in the central dopaminergic pathway in rats. The supersensitivity of the dopaminergic system which developed after denervation is also discussed.", "contents": "Adenosine 3',5'-cyclic monophosphate as a possible mediator of rotational behaviour induced by dopaminergic receptor stimulation in rats lesioned unilaterally in the substantia nigra. A possible involvement of c-AMP in the rotational behaviour induced by a stimulation of dopamine receptors in corpus striatum of rats was investigated. Rats were lesioned unilaterally in the substantia nigra with 6-hydroxydopamine. Intraventricular injection of dopamine, norepinephrine and apomorphine induced rotational behaviour towards the intact side as did dibutyryl c-AMP (dB-c-AMP). Dopamine, norepinephrine and apomorphine could activate adenylate cyclase in homogenates of caudate nucleus. The activation by dopamine was blocked by haloperidol. I.p. injected apomorphine increased c-AMP content bilaterally in caudate nucleus and caused turning towards the intact side; theophylline potentiated and haloperidol blocked the effect. In non-lesioned rats, dopamine and norepinephrine, when injected unilaterally into the caudate nucleus, elicited truning twoards the non-injected side if the rats were pretreated with reserpine and tranylcypromine. c-AMP and dB-c-AMP given similarly to rats pretreated with theophylline also produced turning towards the non-injected side regardless the pretreatment with reserpine and tranylcypromine. All these results emphasize the possibility that c-AMP acts as a second messenger in the central dopaminergic pathway in rats. The supersensitivity of the dopaminergic system which developed after denervation is also discussed."}
{"id": "PMID:185066", "title": "Cyclic AMP and alpha-receptor-mediated modulation of noradrenaling release from rat brain slices.", "content": "Oxymetazoline (an alpha-receptor agonist) reduced and phentolamine (an alpha-receptor antagonist) increased depolarization-induced release (potassium or electrical field stimulation) of 3H-noradrenaline (NA) from superfused neocortical slices in a dose-dependent way. Inhibition of phosphodiesterase also reduced NA release; this effect could be reversed by phentolamine. Phosphodiesterase inhibition potentiated the effect of oxymetazoline. It is suggested that stimulation of presynaptic alpha-receptors may reduce NA release up to about 60% and that increased cyclic AMP formation might be involved in this modulation.", "contents": "Cyclic AMP and alpha-receptor-mediated modulation of noradrenaling release from rat brain slices. Oxymetazoline (an alpha-receptor agonist) reduced and phentolamine (an alpha-receptor antagonist) increased depolarization-induced release (potassium or electrical field stimulation) of 3H-noradrenaline (NA) from superfused neocortical slices in a dose-dependent way. Inhibition of phosphodiesterase also reduced NA release; this effect could be reversed by phentolamine. Phosphodiesterase inhibition potentiated the effect of oxymetazoline. It is suggested that stimulation of presynaptic alpha-receptors may reduce NA release up to about 60% and that increased cyclic AMP formation might be involved in this modulation."}
{"id": "PMID:185067", "title": "Interaction between ACTH fragments, brain opiate receptors and morphine-induced analgesia.", "content": "The present study confirms that N-terminal fragments of ACTH have an affinity for rat brain opiate receptors in vitro. Such peptides, devoid of corticotrophic activity, were found to inhibit morphine-induced analgesia if they also possessed affinity for opiate receptors in vitro. The structure-activity relationship for these two parameters is comparable to that observed for the same peptides on the induction of excessive grooming.", "contents": "Interaction between ACTH fragments, brain opiate receptors and morphine-induced analgesia. The present study confirms that N-terminal fragments of ACTH have an affinity for rat brain opiate receptors in vitro. Such peptides, devoid of corticotrophic activity, were found to inhibit morphine-induced analgesia if they also possessed affinity for opiate receptors in vitro. The structure-activity relationship for these two parameters is comparable to that observed for the same peptides on the induction of excessive grooming."}
{"id": "PMID:185068", "title": "Neuronal peptide (enkephalin) receptors in the ear artery of the rabbit.", "content": "Methionine-enkephalin methylester (MEM) and leucine-enkephalin (LE) inhabit the vasoconstrictor responses of the rabbit ear artery to nerve stimulation by acting on a specific neuronal peptide (enkephalin)-receptor insensitive to opiate agonists. The tetrapeptide: H-Tyr-Gly-Phe-Leu-OCH3 is ineffective. This is the first instance of enkephalins acting in an organ devoid of receptors. In a new test for the analysis of opiate receptors, MEM (ID50=6.9 X 10(-9) M) was a potent inhibitor of transmission. The presence was shown of opiate receptors in the brain which were insensitive to high i.v. or intraventricular doses of enkephalins. It is concluded that enkephalins are not natural ligands to the opiate receptors, but that some of the receptors confuse these structures because of similar characteristics which determine the binding of both opiates and peptides.", "contents": "Neuronal peptide (enkephalin) receptors in the ear artery of the rabbit. Methionine-enkephalin methylester (MEM) and leucine-enkephalin (LE) inhabit the vasoconstrictor responses of the rabbit ear artery to nerve stimulation by acting on a specific neuronal peptide (enkephalin)-receptor insensitive to opiate agonists. The tetrapeptide: H-Tyr-Gly-Phe-Leu-OCH3 is ineffective. This is the first instance of enkephalins acting in an organ devoid of receptors. In a new test for the analysis of opiate receptors, MEM (ID50=6.9 X 10(-9) M) was a potent inhibitor of transmission. The presence was shown of opiate receptors in the brain which were insensitive to high i.v. or intraventricular doses of enkephalins. It is concluded that enkephalins are not natural ligands to the opiate receptors, but that some of the receptors confuse these structures because of similar characteristics which determine the binding of both opiates and peptides."}
{"id": "PMID:185069", "title": "Effect of normorphine and enkephalin on spontaneous potentials in the vas deferens.", "content": "Spontaneous excitatory junction potentials were recorded intracellularly from the smooth muscle of the mouse vas deferens. Exposure of the vas deferens to either normorphine (1 muM) or methionine-enkephalin (0.5 muM) did not alter the frequency or amplitude distribution of the spontaneous potentials. The possible mechanisms by which the narcotic agonists depress the release of noradrenaline on nerve stimulation without inhibiting the spontaneous release of noradrenaline are discussed.", "contents": "Effect of normorphine and enkephalin on spontaneous potentials in the vas deferens. Spontaneous excitatory junction potentials were recorded intracellularly from the smooth muscle of the mouse vas deferens. Exposure of the vas deferens to either normorphine (1 muM) or methionine-enkephalin (0.5 muM) did not alter the frequency or amplitude distribution of the spontaneous potentials. The possible mechanisms by which the narcotic agonists depress the release of noradrenaline on nerve stimulation without inhibiting the spontaneous release of noradrenaline are discussed."}
{"id": "PMID:185070", "title": "3H-noradrenaline outflow induced from isolated aventitia and intima-media of rabbit aorta by electrical field stimulation.", "content": "Electrical field stimulation of the isolated adventitial and intima-medial layers of rabbit aorta preloaded with 3H-noradrenaline elicited a 3H outflow. The initial 3H outflow from adventitia was independent of external Ca2+ concentration. Each of the subsequent 3H outflows was mainly Ca2+ sensitive. All stimulation-induced 3H outflows from media were Ca2+ insensitive. It is concluded that the isolated adventitia is a suitable preparation to outflow from aorta is of neuronal and extraneuronal origin.", "contents": "3H-noradrenaline outflow induced from isolated aventitia and intima-media of rabbit aorta by electrical field stimulation. Electrical field stimulation of the isolated adventitial and intima-medial layers of rabbit aorta preloaded with 3H-noradrenaline elicited a 3H outflow. The initial 3H outflow from adventitia was independent of external Ca2+ concentration. Each of the subsequent 3H outflows was mainly Ca2+ sensitive. All stimulation-induced 3H outflows from media were Ca2+ insensitive. It is concluded that the isolated adventitia is a suitable preparation to outflow from aorta is of neuronal and extraneuronal origin."}
{"id": "PMID:185071", "title": "Dependence liability of enkephalin in the myenteric plexus of the guinea pig.", "content": "The endogenous ligands of opiate receptors, methionine-eukephalin and leucine-enkephalin, were tested for their ability to maintain or to reinduce dependence in myenteric plexus-longitudinal muscle strips taken from tolerant/dependent guinea pigs. Both peptides fully substituted for the function morphine exerts in this preparation. It is concluded that the enkephalins posses a high degree of dependence liability.", "contents": "Dependence liability of enkephalin in the myenteric plexus of the guinea pig. The endogenous ligands of opiate receptors, methionine-eukephalin and leucine-enkephalin, were tested for their ability to maintain or to reinduce dependence in myenteric plexus-longitudinal muscle strips taken from tolerant/dependent guinea pigs. Both peptides fully substituted for the function morphine exerts in this preparation. It is concluded that the enkephalins posses a high degree of dependence liability."}
{"id": "PMID:185081", "title": "The role of cyclic adenosine monophosphate in the swarming phenomenon of Proteus mirabilis.", "content": "The levels of cylic AMP and adenyl cyclase in swarming and non-swarming cells of Proteus mirabilis and the effect of glucose on swarming have been investigated. The results indicate the cAMP is required for swarming, but that the flagellar derepression characteristic of swarming does not result from increased cAMP levels.", "contents": "The role of cyclic adenosine monophosphate in the swarming phenomenon of Proteus mirabilis. The levels of cylic AMP and adenyl cyclase in swarming and non-swarming cells of Proteus mirabilis and the effect of glucose on swarming have been investigated. The results indicate the cAMP is required for swarming, but that the flagellar derepression characteristic of swarming does not result from increased cAMP levels."}
{"id": "PMID:185084", "title": "Adenyl cyclase activity at different environmental temperatures in the isolated rat anterior pituitary membranes.", "content": "The effect of different environmental temperatures on adenyl cyclase was studied. An increase in temperature appears to increase TRH-induced activity of adenyl cyclase, and possible causes an increases sensitivity to the hormone. Cyclic AMP levels of the pituitaries showed change at different environmental temperatures.", "contents": "Adenyl cyclase activity at different environmental temperatures in the isolated rat anterior pituitary membranes. The effect of different environmental temperatures on adenyl cyclase was studied. An increase in temperature appears to increase TRH-induced activity of adenyl cyclase, and possible causes an increases sensitivity to the hormone. Cyclic AMP levels of the pituitaries showed change at different environmental temperatures."}
{"id": "PMID:185091", "title": "Actinomycin D peritonitis in the rat.", "content": "Following intraperitoneal injection of actinomycin D rats show a decrease in number of cells present in the peritoneal cavity, reaching the lowest point after 24 hr. At the same time a highly significant increase of free beta-glucoronidase and of the intracellular concentrations of both cyclic AMP and cyclic GMP has been observed. No exudate was present at this time. Measurable quantities of exudate were present 48-72 hr after actinomycin injection concomitantly with an intense cellular immigration, the dominant cell being mononuclears. In this second phase of the reaction the free beta-glucuronidase decreases towards normal values and both the cyclic nucleotides are significantly below the control values. It is suggested that the increase of intracellular cAMP--concomitant with the maximum release of lysosomal enzymes--is a feedback mechanism preventing further release of inflammatory mediators.", "contents": "Actinomycin D peritonitis in the rat. Following intraperitoneal injection of actinomycin D rats show a decrease in number of cells present in the peritoneal cavity, reaching the lowest point after 24 hr. At the same time a highly significant increase of free beta-glucoronidase and of the intracellular concentrations of both cyclic AMP and cyclic GMP has been observed. No exudate was present at this time. Measurable quantities of exudate were present 48-72 hr after actinomycin injection concomitantly with an intense cellular immigration, the dominant cell being mononuclears. In this second phase of the reaction the free beta-glucuronidase decreases towards normal values and both the cyclic nucleotides are significantly below the control values. It is suggested that the increase of intracellular cAMP--concomitant with the maximum release of lysosomal enzymes--is a feedback mechanism preventing further release of inflammatory mediators."}
{"id": "PMID:185093", "title": "Angiotensin antogonists as pharmacological tools.", "content": "The availability of specific competitive antagonists stimulated investigation of the physiological and pathological role of angiotensin (A-II) and permitted the qualitative and quantitative characterization of numerous angiotensin receptor sites. The specific, competitive antogonists for A-II inhibit both the direct actions of A-II on isolated smooth muscle preparations and the stimulation of specific vascular receptor sites by which A-II evokes prostaglandin biosynthesis and release. Converting enzyme inhibitors a) block the action of exogenous A-I; b) lower blood pressure in conditions associated with high plasma renin levels (e.g., two-kidney renal hypertension, dehydrated diabetes insipidus rats, or in hemorrhagic shock); c) enhance responses to exogenous bradykinin (by inhibiting bradykininase); but d) do not block the effects of A-II at its receptor sites. A-II-receptor antagonists a) block the action of both A-I and A-II, b) lower blood pressure in high renin states, but c) have no effect on bradykinin degradation or action. Angiotensin receptor and synthesis antagonists have been shown to decrease the overall peripheral resistance and to reverse the renal cortical vasoconstriction during hemorrhagic shock and to prolong survival time in hemorrhaged dogs. It is our belief that angiotensin antogonists have therapeutic potential in hemorrhagic shock and would be expected (alone or in combination with alpha-andrenergic blockade) to overcome vascular shutdown and enhance organ perfusion (especially in the kidney).", "contents": "Angiotensin antogonists as pharmacological tools. The availability of specific competitive antagonists stimulated investigation of the physiological and pathological role of angiotensin (A-II) and permitted the qualitative and quantitative characterization of numerous angiotensin receptor sites. The specific, competitive antogonists for A-II inhibit both the direct actions of A-II on isolated smooth muscle preparations and the stimulation of specific vascular receptor sites by which A-II evokes prostaglandin biosynthesis and release. Converting enzyme inhibitors a) block the action of exogenous A-I; b) lower blood pressure in conditions associated with high plasma renin levels (e.g., two-kidney renal hypertension, dehydrated diabetes insipidus rats, or in hemorrhagic shock); c) enhance responses to exogenous bradykinin (by inhibiting bradykininase); but d) do not block the effects of A-II at its receptor sites. A-II-receptor antagonists a) block the action of both A-I and A-II, b) lower blood pressure in high renin states, but c) have no effect on bradykinin degradation or action. Angiotensin receptor and synthesis antagonists have been shown to decrease the overall peripheral resistance and to reverse the renal cortical vasoconstriction during hemorrhagic shock and to prolong survival time in hemorrhaged dogs. It is our belief that angiotensin antogonists have therapeutic potential in hemorrhagic shock and would be expected (alone or in combination with alpha-andrenergic blockade) to overcome vascular shutdown and enhance organ perfusion (especially in the kidney)."}
{"id": "PMID:185094", "title": "Structure--activity relations of antagonists of the renin--angiotensin system.", "content": "In this review, inhibitors of the renin-angiotensin system, both naturally occurring and synthetic, are considered. Inhibition of renin itself, of converting enzyme (dipeptidyl carboxypeptidase), and of interaction with the receptor is characterized from the point of view of mechanism, structure-activity relations, and future developments. The concept of transition state analog and its relevance to the inhibition of renin by pepstatin is discussed. Questions concerning selectivity, increased affinity, and longer duration of action are raised with regard to future design of inhibitors of the renin-angiotensin system.", "contents": "Structure--activity relations of antagonists of the renin--angiotensin system. In this review, inhibitors of the renin-angiotensin system, both naturally occurring and synthetic, are considered. Inhibition of renin itself, of converting enzyme (dipeptidyl carboxypeptidase), and of interaction with the receptor is characterized from the point of view of mechanism, structure-activity relations, and future developments. The concept of transition state analog and its relevance to the inhibition of renin by pepstatin is discussed. Questions concerning selectivity, increased affinity, and longer duration of action are raised with regard to future design of inhibitors of the renin-angiotensin system."}
{"id": "PMID:185095", "title": "Renin--angiotensin antagonists and the regulation of blood pressure.", "content": "The role of the renin--angiotensin system in the regulation of blood pressure in dogs and in human subjects was assessed by the use of the nonapeptide converting enzyme inhibitor (CEI), permitting the following conclusions: 1) In the normal, sodium replete dog, the renin--angiotensin system plays little role in the regulation of blood pressure. 2) As sodium depletion progresses, the renin--angiotensin system becomes increasingly important in the maintenance of blood pressure. In the markedly hypovolemic animal, blocking the conversion of angiotensin I to angiotensin II leads to prolonged hypotension of shock-like levels. 3) The renin--angiotensin system is responsible for the initiation of renovascular hypertension. Blood pressure does not rise during chronic renal artery constriction when the generation of angiotensin II is prevented by the CEI. Although angiotensin II is essential for the initiation of the elevated blood pressure, the renin--angiotensin system plays a decreasing role in the maintenance of the chronic hypertension as sodium and water are retained, and plasma volume increases. 4) In congestive failure induced in the conscious dog by circulatory impairment, the renin--angiotensin--aldosterone system plays an essential role in the compensatory response. During chronic administration of the CEI, the animal cannot compensate even for a relatively mild degree of constriction, and remains hypotensive. In the dog with congestive failure, as in the dog with renovascular hypertension, plasma renin activity (PRA) and plasma aldosterone are elevated early in the syndrome; during this phase, injection of the nonapeptide produces a marked drop in blood pressure. With the retention of sodium and water, and expansion of plasma and extravascular fluid volumes, PRA and plasma aldosterone return to control levels in the new steady state. The inhibitor no longer produces a drop in blood pressure. Thus, the sequential changes in the renin--angiotensin--aldosterone system are remarkably similar in renovascular hypertension and congestive failure. 5) In the normal, salt replete human subject the renin--angiotensin system plays little role in the regulation of blood pressure either in the recumbent or upright posture. However, with relatively mild sodium depletion, the CEI transiently lowers blood pressure even in the recumbent subject. In the absence of angiotensin II such sodium-depleted subjects are unable to compensate when tilted upright, and faint within minutes.", "contents": "Renin--angiotensin antagonists and the regulation of blood pressure. The role of the renin--angiotensin system in the regulation of blood pressure in dogs and in human subjects was assessed by the use of the nonapeptide converting enzyme inhibitor (CEI), permitting the following conclusions: 1) In the normal, sodium replete dog, the renin--angiotensin system plays little role in the regulation of blood pressure. 2) As sodium depletion progresses, the renin--angiotensin system becomes increasingly important in the maintenance of blood pressure. In the markedly hypovolemic animal, blocking the conversion of angiotensin I to angiotensin II leads to prolonged hypotension of shock-like levels. 3) The renin--angiotensin system is responsible for the initiation of renovascular hypertension. Blood pressure does not rise during chronic renal artery constriction when the generation of angiotensin II is prevented by the CEI. Although angiotensin II is essential for the initiation of the elevated blood pressure, the renin--angiotensin system plays a decreasing role in the maintenance of the chronic hypertension as sodium and water are retained, and plasma volume increases. 4) In congestive failure induced in the conscious dog by circulatory impairment, the renin--angiotensin--aldosterone system plays an essential role in the compensatory response. During chronic administration of the CEI, the animal cannot compensate even for a relatively mild degree of constriction, and remains hypotensive. In the dog with congestive failure, as in the dog with renovascular hypertension, plasma renin activity (PRA) and plasma aldosterone are elevated early in the syndrome; during this phase, injection of the nonapeptide produces a marked drop in blood pressure. With the retention of sodium and water, and expansion of plasma and extravascular fluid volumes, PRA and plasma aldosterone return to control levels in the new steady state. The inhibitor no longer produces a drop in blood pressure. Thus, the sequential changes in the renin--angiotensin--aldosterone system are remarkably similar in renovascular hypertension and congestive failure. 5) In the normal, salt replete human subject the renin--angiotensin system plays little role in the regulation of blood pressure either in the recumbent or upright posture. However, with relatively mild sodium depletion, the CEI transiently lowers blood pressure even in the recumbent subject. In the absence of angiotensin II such sodium-depleted subjects are unable to compensate when tilted upright, and faint within minutes."}
{"id": "PMID:185100", "title": "The secretion of lysosomal enzymes.", "content": "The studies reviewed in this chapter provide further evidence that the secretion of lysosomal enzymes and other hydrolases is a constitutive function of certain cells whereas in other cells is an inducible process probably contributing to the pathology of a variety of diseases. Little is known of the mechanisms mediating the secretion of lysosomal enzymes. We have summarized evidence suggesting a role of microfilaments and microtubules in controlling enzyme release, but further studies of the biochemical mechanisms which control the activity of these subcellular structures are required. The fusion of lysosomes with the plasma membrane has been observed in several situations and the mechanisms underlying processes of this nature have been studied in lower organisms (Satir et al. 1973; Plattner 1974). Agents, such as concanavalin A,  which interfere with the fusion of endosomes with lysosomes (Goldman 1974; Edelson and Cohn 1974a, b) should also be useful in determining the chemical nature of membrane components involved in the fusion process. New information on the fate of secreted acid hydrolases has been obtained from studies of the uptake of lysosomal enzymes by fibroblasts. Clearly, the mechanisms by which these cells endocytose secreted lysosomal enzymes will be a subject for detailed study in view of the important of directing enzymes and drugs into lysosomes (De Duve et al. 1974). The mechanisms by which extracellular inhibitors inactivate hydrolytic enzymes, particularly proteinases, is also being clarified (for review see Davies 1975) and this should aid in finding new ways for preventing tissue damage caused by the excessive secretion of these enzymes. Further investigation concerning the secretion of lysosomal enzymes should establish the essential physiological role which these enzymes play at both extracellular and intracellular sites. Also, a close examination of the interaction of both endogenous and exogenous stimuli of inflammation with cells resulting in the secretion of hydrolytic enzymes, will clarify the mechanisms underlying the initiation and progression of the inflammatory process in its diverse forms.", "contents": "The secretion of lysosomal enzymes. The studies reviewed in this chapter provide further evidence that the secretion of lysosomal enzymes and other hydrolases is a constitutive function of certain cells whereas in other cells is an inducible process probably contributing to the pathology of a variety of diseases. Little is known of the mechanisms mediating the secretion of lysosomal enzymes. We have summarized evidence suggesting a role of microfilaments and microtubules in controlling enzyme release, but further studies of the biochemical mechanisms which control the activity of these subcellular structures are required. The fusion of lysosomes with the plasma membrane has been observed in several situations and the mechanisms underlying processes of this nature have been studied in lower organisms (Satir et al. 1973; Plattner 1974). Agents, such as concanavalin A,  which interfere with the fusion of endosomes with lysosomes (Goldman 1974; Edelson and Cohn 1974a, b) should also be useful in determining the chemical nature of membrane components involved in the fusion process. New information on the fate of secreted acid hydrolases has been obtained from studies of the uptake of lysosomal enzymes by fibroblasts. Clearly, the mechanisms by which these cells endocytose secreted lysosomal enzymes will be a subject for detailed study in view of the important of directing enzymes and drugs into lysosomes (De Duve et al. 1974). The mechanisms by which extracellular inhibitors inactivate hydrolytic enzymes, particularly proteinases, is also being clarified (for review see Davies 1975) and this should aid in finding new ways for preventing tissue damage caused by the excessive secretion of these enzymes. Further investigation concerning the secretion of lysosomal enzymes should establish the essential physiological role which these enzymes play at both extracellular and intracellular sites. Also, a close examination of the interaction of both endogenous and exogenous stimuli of inflammation with cells resulting in the secretion of hydrolytic enzymes, will clarify the mechanisms underlying the initiation and progression of the inflammatory process in its diverse forms."}
{"id": "PMID:185101", "title": "[In vitro assay for ACTH-releasing activity using ACTH radioimmunoassay: ACTH releasing activities by various drugs (author's transl)].", "content": "Several procedures have been reported for the assay of corticotrophine-releasing factor (CRF), each having its advantages and disadvantages. This report deals with an in vitro assay of ACTH releasing activity utilizing pituitary incubation combined with ACTH radioimmunoassay. Rat half pituitary was preincubated in 2 ml Krebs Ringer bicarbonate buffer containing 0.2% glucose and 0.25 % BSA (KRBG-BSA) for 1.5 hr (45 min X 2). The medium was replaced by 1 ml KRBG-BSA and incubated for 30 min. Then the medium was again replaced by 1 ml KRBG-BSA or KRBG-BSA containing test materials and incubated for another 30 min. The amount of ACTH assayed by radioimmunoassay in the 2nd 30 min incubation was compared with in the 1st 30 min incubation and expressed as percentage. In ACTH radioimmunoassay, anti-ACTH serum was diluted to 1 : 1,500-3,000. The 125I-alpha 1-24ACTH-antibody system was not affected by lysine-vasopressin (LVP), arginine-vasopressin (AVP), rat's pituitary LH, GH and prolactin. Human 1-39ACTH was used as ACTH standard, and the dilution curve of incubation medium was paralleled with the standard curve. Repeatability of immunoassayable ACTH within-assay was 174 +/- 5.0 pg/tube (CV = 2.9%). A log dose-relationship was observed between the amounts of stalk median eminence extracts (SME ; NIAMDD) added to the incubation medium and its ACTH releasing activities. The sensitivity of this assay method was at least 0.1 SME or 10 mU of LVP and AVP. Using this method, it found that LVP, AVP, norepinephrine (100 ng/ml200 ng/ml) and 5-hydroxytryptophane (1 mug/ml) had ACTH releasing activities but LH-RH, TRH, glucagon, dopamine, phentolamine, propranolol, haloperidol, prostaglandin E1 and indomethacin did not affect the release of ACTH.", "contents": "[In vitro assay for ACTH-releasing activity using ACTH radioimmunoassay: ACTH releasing activities by various drugs (author's transl)]. Several procedures have been reported for the assay of corticotrophine-releasing factor (CRF), each having its advantages and disadvantages. This report deals with an in vitro assay of ACTH releasing activity utilizing pituitary incubation combined with ACTH radioimmunoassay. Rat half pituitary was preincubated in 2 ml Krebs Ringer bicarbonate buffer containing 0.2% glucose and 0.25 % BSA (KRBG-BSA) for 1.5 hr (45 min X 2). The medium was replaced by 1 ml KRBG-BSA and incubated for 30 min. Then the medium was again replaced by 1 ml KRBG-BSA or KRBG-BSA containing test materials and incubated for another 30 min. The amount of ACTH assayed by radioimmunoassay in the 2nd 30 min incubation was compared with in the 1st 30 min incubation and expressed as percentage. In ACTH radioimmunoassay, anti-ACTH serum was diluted to 1 : 1,500-3,000. The 125I-alpha 1-24ACTH-antibody system was not affected by lysine-vasopressin (LVP), arginine-vasopressin (AVP), rat's pituitary LH, GH and prolactin. Human 1-39ACTH was used as ACTH standard, and the dilution curve of incubation medium was paralleled with the standard curve. Repeatability of immunoassayable ACTH within-assay was 174 +/- 5.0 pg/tube (CV = 2.9%). A log dose-relationship was observed between the amounts of stalk median eminence extracts (SME ; NIAMDD) added to the incubation medium and its ACTH releasing activities. The sensitivity of this assay method was at least 0.1 SME or 10 mU of LVP and AVP. Using this method, it found that LVP, AVP, norepinephrine (100 ng/ml200 ng/ml) and 5-hydroxytryptophane (1 mug/ml) had ACTH releasing activities but LH-RH, TRH, glucagon, dopamine, phentolamine, propranolol, haloperidol, prostaglandin E1 and indomethacin did not affect the release of ACTH."}
{"id": "PMID:185102", "title": "[The study of physiological chemistry on a subunit of salivary gland hormone (2) (author's transl)].", "content": "It had been reported by authors that salivary gland hormone, parotin, was composed with subunit (parotin-subunit) which showed molecular weight of 45,000, and that parotin-subunit had rabbit serum calcium decreasing activity and the cross reactivity with rabbit anti parotin serum. In the present report, in order to study physiological chemistry of parotin-subunit, the influence of parotin-subunit on serum Ca and 45Ca levels relating to calcium metabolism, the distribution of 131I-parotin-subunit, the effect of parotin-subunit, on adenyl cyclase-cyclicAMP system, the anabolic action, C-terminal amino acid sequence and sugar component of parotin-subunit were investigated. The results are summarized as follows: 1) The decrease of rabbit serum Ca after injection of parotin-subunit was related to change of Ca in stable bone, but not to inhibition of bone resorption. 2) A high concentrated localization of radioactivity of 131I-parotin-subunit was found in liver, kidney and spleen, and as much as 60% of administrated radioactivity was localized in liver at 5 min after the injection. The retention of radioactivity was found in testis, seminal vesicle, prostate, parotid gland and submaxillary gland. 3) Cyclic AMP level increased significantly in metaphysial bone, submaxillary gland and plasma after administration of parotin-subunit but in other organs with localized much radioactivities, the level did not changed. Parotin-subunit activated adenyl cyclase of particular fraction of metaphysial bone. 4) The C-terminal amino acid of parotin-subunit was Leu, and its C-terminal amino acid sequence was -Val-Ser-Ala-Thr- Leu-OH by digestion of carboxypeptidase A. 5) Parotin-subunit included 3.3% of sugar which consisted of amino sugar and uronic acid.", "contents": "[The study of physiological chemistry on a subunit of salivary gland hormone (2) (author's transl)]. It had been reported by authors that salivary gland hormone, parotin, was composed with subunit (parotin-subunit) which showed molecular weight of 45,000, and that parotin-subunit had rabbit serum calcium decreasing activity and the cross reactivity with rabbit anti parotin serum. In the present report, in order to study physiological chemistry of parotin-subunit, the influence of parotin-subunit on serum Ca and 45Ca levels relating to calcium metabolism, the distribution of 131I-parotin-subunit, the effect of parotin-subunit, on adenyl cyclase-cyclicAMP system, the anabolic action, C-terminal amino acid sequence and sugar component of parotin-subunit were investigated. The results are summarized as follows: 1) The decrease of rabbit serum Ca after injection of parotin-subunit was related to change of Ca in stable bone, but not to inhibition of bone resorption. 2) A high concentrated localization of radioactivity of 131I-parotin-subunit was found in liver, kidney and spleen, and as much as 60% of administrated radioactivity was localized in liver at 5 min after the injection. The retention of radioactivity was found in testis, seminal vesicle, prostate, parotid gland and submaxillary gland. 3) Cyclic AMP level increased significantly in metaphysial bone, submaxillary gland and plasma after administration of parotin-subunit but in other organs with localized much radioactivities, the level did not changed. Parotin-subunit activated adenyl cyclase of particular fraction of metaphysial bone. 4) The C-terminal amino acid of parotin-subunit was Leu, and its C-terminal amino acid sequence was -Val-Ser-Ala-Thr- Leu-OH by digestion of carboxypeptidase A. 5) Parotin-subunit included 3.3% of sugar which consisted of amino sugar and uronic acid."}
{"id": "PMID:185104", "title": "In vitro biosynthesis and release of three immuno-reactive insulin-like components by a human insulinoma.", "content": "Pieces of a human insulinoma were incubated for 120 or 180 min in media containing labelled leucine. In addition to insulin and proinsulin, the tumoral tissue was found to synthesize and release a third immunoreactive insulin-like component of higher molecular weight. No significant amount of the latter component was detected in normal rat islets under identical experimental conditions. The rate of secretion of insulin-like peptides was abnormally high relative to their concentration in the tumoral tissue, and was apparently unaffected by various insulinotropic or inhibitory agents. Only cycloheximide was found to significantly reduce the synthesis and subsequent release of insulin-like peptides by the tumoral tissue. It is suggested that the secretion of large amounts of both the high molecular weight component and proinsulin relative to that of insulin might be due, in part at least, to the inability of the tumoral cells to prevent the release of newly synthetized hormonal peptides, leading to the depletion of the tissue in hormonal products, as judged by both immunological and ultrastructural criteria.", "contents": "In vitro biosynthesis and release of three immuno-reactive insulin-like components by a human insulinoma. Pieces of a human insulinoma were incubated for 120 or 180 min in media containing labelled leucine. In addition to insulin and proinsulin, the tumoral tissue was found to synthesize and release a third immunoreactive insulin-like component of higher molecular weight. No significant amount of the latter component was detected in normal rat islets under identical experimental conditions. The rate of secretion of insulin-like peptides was abnormally high relative to their concentration in the tumoral tissue, and was apparently unaffected by various insulinotropic or inhibitory agents. Only cycloheximide was found to significantly reduce the synthesis and subsequent release of insulin-like peptides by the tumoral tissue. It is suggested that the secretion of large amounts of both the high molecular weight component and proinsulin relative to that of insulin might be due, in part at least, to the inability of the tumoral cells to prevent the release of newly synthetized hormonal peptides, leading to the depletion of the tissue in hormonal products, as judged by both immunological and ultrastructural criteria."}
{"id": "PMID:185109", "title": "Additive effects of norepinephrine and cyclic AMP on the activation of the protein kinase from adipose tissue.", "content": "In this work the kinetics of activation of the cyclic AMP-dependent protein kinase by several catecholamines and ACTH, have been studied in rat epididymal fat pads and isolated fat cells. The method of Soderling and co-workers which permits the measurement of the state of activation of the protein kinase after hormonal stimulation in adipose tissue, has been used. Kinetics experiments where norepinephrine was used showed that the results obtained with isolated cells conform to the models of Sutherland and Brostrom and co-workers. Wtih intact tissue, norepinephrine not only stimulates the protein kinase activity measured without exogenous cyclic AMP but also the total activity measured in the presence of cyclic AMP (5 X 10(-6) M); thus the effect of norepinephrine, obtained during incubation of the tissue, and that of cyclic AMP, added to the soluble fraction after incubation, were additive. This effect seems to be of the beta type because it is blocked completely by propranolol. A weak, additive but significant effect was also obtained with epinephrine and isoproterenol but not with ACTH. Neither cyclic GMP nor cyclic IMP seems implicated in this effect. It was shown that stroma vascular cells which are present in the fat pads are not involved. These results suggest that the effects of norepinephrine on the protein kinase of the fat pads cannot be completely explained by the model of Brostrom and colleagues.", "contents": "Additive effects of norepinephrine and cyclic AMP on the activation of the protein kinase from adipose tissue. In this work the kinetics of activation of the cyclic AMP-dependent protein kinase by several catecholamines and ACTH, have been studied in rat epididymal fat pads and isolated fat cells. The method of Soderling and co-workers which permits the measurement of the state of activation of the protein kinase after hormonal stimulation in adipose tissue, has been used. Kinetics experiments where norepinephrine was used showed that the results obtained with isolated cells conform to the models of Sutherland and Brostrom and co-workers. Wtih intact tissue, norepinephrine not only stimulates the protein kinase activity measured without exogenous cyclic AMP but also the total activity measured in the presence of cyclic AMP (5 X 10(-6) M); thus the effect of norepinephrine, obtained during incubation of the tissue, and that of cyclic AMP, added to the soluble fraction after incubation, were additive. This effect seems to be of the beta type because it is blocked completely by propranolol. A weak, additive but significant effect was also obtained with epinephrine and isoproterenol but not with ACTH. Neither cyclic GMP nor cyclic IMP seems implicated in this effect. It was shown that stroma vascular cells which are present in the fat pads are not involved. These results suggest that the effects of norepinephrine on the protein kinase of the fat pads cannot be completely explained by the model of Brostrom and colleagues."}
{"id": "PMID:185112", "title": "Current concepts of somatomedin and other biologically related growth factors.", "content": "Since the discovery 20 years ago that the growth-promoting effects of somatotropin are mediated through a serum factor(s), research in this area has rapidly expanded. It is the purpose of this review to bring this area of scientific endeavor into perspective. The first part of this review will deal with aspects of total serum somatomedin activity and its biologic actions and measurements in health and disease. The last part of this review will summarize some of the physical and biologic characteristics of the recently purified \"somatomedin-like\" substances: somatomedin A, B, and C, NSILA-S (nonsuppressible insulin-like activity-soluble in acid ethanol) and MSA (multiplication-stimulating activity).", "contents": "Current concepts of somatomedin and other biologically related growth factors. Since the discovery 20 years ago that the growth-promoting effects of somatotropin are mediated through a serum factor(s), research in this area has rapidly expanded. It is the purpose of this review to bring this area of scientific endeavor into perspective. The first part of this review will deal with aspects of total serum somatomedin activity and its biologic actions and measurements in health and disease. The last part of this review will summarize some of the physical and biologic characteristics of the recently purified \"somatomedin-like\" substances: somatomedin A, B, and C, NSILA-S (nonsuppressible insulin-like activity-soluble in acid ethanol) and MSA (multiplication-stimulating activity)."}
{"id": "PMID:185113", "title": "The metabolic fate of plasma lipoproteins in normal subjects and in patients with insulin resistance and endogenous hypertriglyceridaemia.", "content": "Using I131 VLDL selectively labelled in the B-apoprotein and I125 LDL injected simultaneously into the patient we have derived some quantitative measures of VLDL and LDL metabolism in man. The effects of insulin resistance, associated with idiopathic hypertriglyceridaemia, adult onset diabetes and diabetic lipodystrophy on the metabolic behaviour of these molecules were also assessed. In the normal subjects 72-83% of the total daily plasma VLDL B-apoprotein flux was metabolised via a pathway which involved its ultimate conversion to plasma LDL, while 21-28% was degraded without such conversion. The amount of B-apoprotein metabolised by either of these routes was proportionate to the flux rate and the two pathways accounted for the total VLDL B-apoprotein removed from the plasma. In patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics the total plasma VLDL B-apoprotein flux was higher than normal, indicating increased production of this apoprotein. On the other hand, the flux rate of plasma VLDL B-apoprotein in the patients with diabetic lipodystrophy was normal, suggesting that the increase in the circulating mass of these molecules was due to impaired clearance. In all the patients, however, the fractions of the total flux either converted to LDL or degraded were lower than normal, suggesting that insulin resistance limited the removal of this apoprotein by these pathways. The results also indicate that a fraction of the total VLDL removed from the plasma has been retained in an extravascular compartment, possibly representing VLDL molecules trapped in the vascular structures. In the control and the insulin resistant subjects the quantity of LDL apoprotein catabolised per day agreed closely with the amount derived from VLDL B-apoprotein conversion, suggesting that VLDL-B-apoprotein serves as the main source of LDL apoprotein. In patients with idiopathic hypertriglyceridaemia and in adult onset diabetics the absolute turnover rate of plasma LDL apoprotein was higher than normal, while in the lipodystrophic patients it was reduced. It is suggested that the increase in LDL turnover seen in the former groups could be an additive factor in the deposition of lipid rich material in arterial walls.", "contents": "The metabolic fate of plasma lipoproteins in normal subjects and in patients with insulin resistance and endogenous hypertriglyceridaemia. Using I131 VLDL selectively labelled in the B-apoprotein and I125 LDL injected simultaneously into the patient we have derived some quantitative measures of VLDL and LDL metabolism in man. The effects of insulin resistance, associated with idiopathic hypertriglyceridaemia, adult onset diabetes and diabetic lipodystrophy on the metabolic behaviour of these molecules were also assessed. In the normal subjects 72-83% of the total daily plasma VLDL B-apoprotein flux was metabolised via a pathway which involved its ultimate conversion to plasma LDL, while 21-28% was degraded without such conversion. The amount of B-apoprotein metabolised by either of these routes was proportionate to the flux rate and the two pathways accounted for the total VLDL B-apoprotein removed from the plasma. In patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics the total plasma VLDL B-apoprotein flux was higher than normal, indicating increased production of this apoprotein. On the other hand, the flux rate of plasma VLDL B-apoprotein in the patients with diabetic lipodystrophy was normal, suggesting that the increase in the circulating mass of these molecules was due to impaired clearance. In all the patients, however, the fractions of the total flux either converted to LDL or degraded were lower than normal, suggesting that insulin resistance limited the removal of this apoprotein by these pathways. The results also indicate that a fraction of the total VLDL removed from the plasma has been retained in an extravascular compartment, possibly representing VLDL molecules trapped in the vascular structures. In the control and the insulin resistant subjects the quantity of LDL apoprotein catabolised per day agreed closely with the amount derived from VLDL B-apoprotein conversion, suggesting that VLDL-B-apoprotein serves as the main source of LDL apoprotein. In patients with idiopathic hypertriglyceridaemia and in adult onset diabetics the absolute turnover rate of plasma LDL apoprotein was higher than normal, while in the lipodystrophic patients it was reduced. It is suggested that the increase in LDL turnover seen in the former groups could be an additive factor in the deposition of lipid rich material in arterial walls."}
{"id": "PMID:185114", "title": "Clinical correlations of serum proinsulin-like material in islet cell tumours.", "content": "To examine the possibility that the concentration of circulating proinsulin-like material (PLM) might be helpful in evaluating the therapeutic response of patients with islet cell tumours, serum levels of PLM in three patients with islet cell tumours were correlated with hypoglycaemic symptoms and plasma glucose concentrations before and after treatment. In two patients ranges of fasting PLM concentration were 0.21-0.29 and 0.91-0.93 ng/ml, respectively, before treatment. After surgical excision of their islet cell adenomas, PLM concentrations decreased to 0.06-0.09 and 0.03-0.05 ng/ml. Insulin concentrations were low preoperatively in both patients and were unchanged postoperatively. The resulting relief from hypoglycaemia was paralleled by a reduction of PLM, with no significant change in insulin. In a third patient, treatment with streptozotocin resulted in marked symptomatic improvement, a 65% reduction in PLM concentration, but no significant change in insulin levels. Relapse was associated with increasing frequency of hypoglycaemic symptoms and increasing PLM concentrations. These findings suggest that changes in the levels of serum PLM may prove to be a sensitive indicator of the response of islet cell tumours to therapy.", "contents": "Clinical correlations of serum proinsulin-like material in islet cell tumours. To examine the possibility that the concentration of circulating proinsulin-like material (PLM) might be helpful in evaluating the therapeutic response of patients with islet cell tumours, serum levels of PLM in three patients with islet cell tumours were correlated with hypoglycaemic symptoms and plasma glucose concentrations before and after treatment. In two patients ranges of fasting PLM concentration were 0.21-0.29 and 0.91-0.93 ng/ml, respectively, before treatment. After surgical excision of their islet cell adenomas, PLM concentrations decreased to 0.06-0.09 and 0.03-0.05 ng/ml. Insulin concentrations were low preoperatively in both patients and were unchanged postoperatively. The resulting relief from hypoglycaemia was paralleled by a reduction of PLM, with no significant change in insulin. In a third patient, treatment with streptozotocin resulted in marked symptomatic improvement, a 65% reduction in PLM concentration, but no significant change in insulin levels. Relapse was associated with increasing frequency of hypoglycaemic symptoms and increasing PLM concentrations. These findings suggest that changes in the levels of serum PLM may prove to be a sensitive indicator of the response of islet cell tumours to therapy."}
{"id": "PMID:185115", "title": "[Participation of the beta-receptor system in the genesis of the carotid aortic baroreceptor reflex in the dog (author's transl)].", "content": "The effects of propranolol, given by close arterial injection, on the reflex vasodilatation induced in the atropinized isolated gracilis muscle by rapid i.v. administration of norepinephrine were studied in dogs. The integrated areas of vasodilatation were significantly reduced after treatment with propranolol. Thus the conclusion was that adrenergic beta-receptors participate in the reflex vasodilatation, although how they act needs further elucidation.", "contents": "[Participation of the beta-receptor system in the genesis of the carotid aortic baroreceptor reflex in the dog (author's transl)]. The effects of propranolol, given by close arterial injection, on the reflex vasodilatation induced in the atropinized isolated gracilis muscle by rapid i.v. administration of norepinephrine were studied in dogs. The integrated areas of vasodilatation were significantly reduced after treatment with propranolol. Thus the conclusion was that adrenergic beta-receptors participate in the reflex vasodilatation, although how they act needs further elucidation."}
{"id": "PMID:185117", "title": "Changes in lactic dehydrogenase isoenzymes after hepatic artery ligation in patients with hepatic carcinoma.", "content": "Serum activities of LDH isoenzymes as well as total LDH, GOT and GPT were determined after hepatic artery ligation in five patients with primary or metastatic liver cancer. Transaminases and total LDH activities were raised after the operation showing their peaks on the first or third postoperative days. LDH2, LDH3 and LDH5 increased substantially during the first three postoperative days. These changes became nearly normalized within two weeks after hepatic artery ligation. As control the same enzymatic activities were measured in eight patients after usual laparotomies but no significant abnormalities were observed postoperatively. Thus, liberation of not only cathodic but also anodic migrating LDH isoenzymes seems to ensue possibly after acute liver damage induced by hepatic artery ligation. This study also suggests that serial determination of LDH isoenzymes as well as its total activity could be a valuable assessment for evaluating the anti-tumor effect of hepatic artery ligation.", "contents": "Changes in lactic dehydrogenase isoenzymes after hepatic artery ligation in patients with hepatic carcinoma. Serum activities of LDH isoenzymes as well as total LDH, GOT and GPT were determined after hepatic artery ligation in five patients with primary or metastatic liver cancer. Transaminases and total LDH activities were raised after the operation showing their peaks on the first or third postoperative days. LDH2, LDH3 and LDH5 increased substantially during the first three postoperative days. These changes became nearly normalized within two weeks after hepatic artery ligation. As control the same enzymatic activities were measured in eight patients after usual laparotomies but no significant abnormalities were observed postoperatively. Thus, liberation of not only cathodic but also anodic migrating LDH isoenzymes seems to ensue possibly after acute liver damage induced by hepatic artery ligation. This study also suggests that serial determination of LDH isoenzymes as well as its total activity could be a valuable assessment for evaluating the anti-tumor effect of hepatic artery ligation."}
{"id": "PMID:185118", "title": "Receptors for morphine and opioids.", "content": "Two points concerning enzymatic systems acting on disposal of morphine are discussed, namely the multiplicity of glucuronyltransferase and the effect of nalorphine on N-demethylation of morphine. Evidences of the presence of at least two different glucuronyltransferases in microsomes of rat liver, kidney and intestine are presented. These evidences are given by the different distribution of the glucuronizing activity for morphine and rho-nitrophenol in microsomal preparations of these organs; by the different glucuronidation activity for both substrates induced by phenobarbital and 3-methylcholantrene; and finally by the chromatographic separation of fractions with enzymatic glucuronidating activity only for rho-nitrophenol or only for morphine. Nalorphine in concentrations of 1.3 X 10(-3) M and 1.3 X 10(-4) M inhibited in vitro de-N-demethylation of morphine 1.3 X 10(-3) M by the supernatant of rat liver homogenates, while in concentration of 1.3 X 10(-5) M it enhanced this reaction.", "contents": "Receptors for morphine and opioids. Two points concerning enzymatic systems acting on disposal of morphine are discussed, namely the multiplicity of glucuronyltransferase and the effect of nalorphine on N-demethylation of morphine. Evidences of the presence of at least two different glucuronyltransferases in microsomes of rat liver, kidney and intestine are presented. These evidences are given by the different distribution of the glucuronizing activity for morphine and rho-nitrophenol in microsomal preparations of these organs; by the different glucuronidation activity for both substrates induced by phenobarbital and 3-methylcholantrene; and finally by the chromatographic separation of fractions with enzymatic glucuronidating activity only for rho-nitrophenol or only for morphine. Nalorphine in concentrations of 1.3 X 10(-3) M and 1.3 X 10(-4) M inhibited in vitro de-N-demethylation of morphine 1.3 X 10(-3) M by the supernatant of rat liver homogenates, while in concentration of 1.3 X 10(-5) M it enhanced this reaction."}
{"id": "PMID:185119", "title": "Tachyphylaxis and angiotensin receptors.", "content": "Angiotensin tachyphylaxis was studied in the isolated guinea pig ileum under isometric conditions. 2. In tachyphylactic organs, the initial phasic response to angiotensin was abolished, while the tonic component of the response became faster in its onset and in its reversal (relaxation). 3. The relaxation of non-tachyphylactic organs after angiotensin washout was significantly slower than with bradykinin, des-amino-angiotensin and hexanoyl-angiotensin. This difference did not occur in tachyphylactic organs. 4. There was no correlation between production of tachyphylaxis or rate of relaxation after washout and the partition coefficient of the four peptides in an organic:aqueous solvent system. 5. It is suggested that tachyphylaxis depends on a slowly reversible alteration of a calcium translocation step in the stimulus-response coupling.", "contents": "Tachyphylaxis and angiotensin receptors. Angiotensin tachyphylaxis was studied in the isolated guinea pig ileum under isometric conditions. 2. In tachyphylactic organs, the initial phasic response to angiotensin was abolished, while the tonic component of the response became faster in its onset and in its reversal (relaxation). 3. The relaxation of non-tachyphylactic organs after angiotensin washout was significantly slower than with bradykinin, des-amino-angiotensin and hexanoyl-angiotensin. This difference did not occur in tachyphylactic organs. 4. There was no correlation between production of tachyphylaxis or rate of relaxation after washout and the partition coefficient of the four peptides in an organic:aqueous solvent system. 5. It is suggested that tachyphylaxis depends on a slowly reversible alteration of a calcium translocation step in the stimulus-response coupling."}
{"id": "PMID:185120", "title": "Relative responsiveness (rho): a critical analysis of a new method in receptor differentiation.", "content": "The rho ratio, which measures the capability of a receptor system to induce a maximal contraction after saturation by a full agonist was analysed from the standpoint of its variability considering the values obtained either for a given receptor system in the same type of preparation or for different types of preparation. This variability was discussed on the grounds of receptor theory, as the basis for a new method in receptor differentiation.", "contents": "Relative responsiveness (rho): a critical analysis of a new method in receptor differentiation. The rho ratio, which measures the capability of a receptor system to induce a maximal contraction after saturation by a full agonist was analysed from the standpoint of its variability considering the values obtained either for a given receptor system in the same type of preparation or for different types of preparation. This variability was discussed on the grounds of receptor theory, as the basis for a new method in receptor differentiation."}
{"id": "PMID:185121", "title": "Evidence of depolarization-induced cAMP increase in the superior cervical ganglion of several mammalian species.", "content": "1. The activation of cAMP synthesis resulting from exposure of superior cervical ganglion (SCG) tissue to high K+ solutions observed in calf has been found to occur in three other mammalian species, namely rat, cat, and rabbit. 2. The cAMP accumulation in the ganglion of calf is much less pronounced than that occurring in the other species. The enhancing effect oftheophylline on the increase of cAMP was found to be much greater in the SCG of calf than in that of other species. When veratridine was used as the depolarizing agent the species differences were found to be similar to those observed after potassium stimulation. 3. The effectiveness of several other depolarizing agents in causing an increase in the cAMP level was tested in rabbit SCG.", "contents": "Evidence of depolarization-induced cAMP increase in the superior cervical ganglion of several mammalian species. 1. The activation of cAMP synthesis resulting from exposure of superior cervical ganglion (SCG) tissue to high K+ solutions observed in calf has been found to occur in three other mammalian species, namely rat, cat, and rabbit. 2. The cAMP accumulation in the ganglion of calf is much less pronounced than that occurring in the other species. The enhancing effect oftheophylline on the increase of cAMP was found to be much greater in the SCG of calf than in that of other species. When veratridine was used as the depolarizing agent the species differences were found to be similar to those observed after potassium stimulation. 3. The effectiveness of several other depolarizing agents in causing an increase in the cAMP level was tested in rabbit SCG."}
{"id": "PMID:185124", "title": "When drug therapy for lung disease affects the heart.", "content": "The development of effective drugs for chronic lung disease, especially bronchodilator aerosols, has been a boon to patients and physicians alike, but these agents also may provoke arrhythmias. Fluorocarbon propellants, once regarded as harmless, are now known to disrupt cardiac function, sensitizing the heart to the arrhythmic effects of sympathomimetic amines. Catecholamine drugs as a group have a strong impact on heart rate and contractility. But the danger of rhythm disturbances often can be reduced by cutting the dosage or choosing a preparation with more beta 2 activity. Methylxanthines, generally safer than catecholamines, nevertheless must be used with caution and preferably alone in patients with heart and lung disease.", "contents": "When drug therapy for lung disease affects the heart. The development of effective drugs for chronic lung disease, especially bronchodilator aerosols, has been a boon to patients and physicians alike, but these agents also may provoke arrhythmias. Fluorocarbon propellants, once regarded as harmless, are now known to disrupt cardiac function, sensitizing the heart to the arrhythmic effects of sympathomimetic amines. Catecholamine drugs as a group have a strong impact on heart rate and contractility. But the danger of rhythm disturbances often can be reduced by cutting the dosage or choosing a preparation with more beta 2 activity. Methylxanthines, generally safer than catecholamines, nevertheless must be used with caution and preferably alone in patients with heart and lung disease."}
{"id": "PMID:185125", "title": "Differential utilization of manpower.", "content": "Employers often ignore the different levels of skill among social workers and regard the non-MSW as merely a less expensive, second choice after the MSW for the same job. The author discusses a more productive allocation of work among MSWs and BSWs and describes its application in a medical setting.", "contents": "Differential utilization of manpower. Employers often ignore the different levels of skill among social workers and regard the non-MSW as merely a less expensive, second choice after the MSW for the same job. The author discusses a more productive allocation of work among MSWs and BSWs and describes its application in a medical setting."}
{"id": "PMID:185126", "title": "Social work services in a high-risk nursery.", "content": "Why should a social worker be on the team of a neonatal intensive-care nursery? Helping parents cope with the crises that arise with high-risk births is only one important reason. Ameliorating staff stress is another. Also, by following up the high-risk babies, the social worker has an opportunity to play a preventive role.", "contents": "Social work services in a high-risk nursery. Why should a social worker be on the team of a neonatal intensive-care nursery? Helping parents cope with the crises that arise with high-risk births is only one important reason. Ameliorating staff stress is another. Also, by following up the high-risk babies, the social worker has an opportunity to play a preventive role."}
{"id": "PMID:185127", "title": "[Effects of monoamine-related compounds on the sleep-awake cycle in rabbits].", "content": "The role of 5HT and NA in the regulation of the sleep-awake cycle, especially in the triggering mechanisms of paradoxical sleep (PT), was studied in rabbits using reserpine, parachlorophenylalanine (PCPA), alpha-methyl-p-tyrosine (alpha-MT) and alpha-methyl -m-tyrosine (alpha-MMT). 1) Reserpine (0.5 mg/kg, i.v.) caused a diphasic action on the brain electrical activity in rabbits: an initial activation pattern in the EEG which continued to 2approximately3 hr, was followed gradually by a slow wave. Forty to sixty min after reserpine administration, spike waves resembling the PGO waves in cats appeared from the medial nucleus Trapezoides (Trap. m.) in rabbits. From the electrophysiological point of view, these spike waves (reserpine spike waves) were in many respects similar to those recorded during PS (TR spike waves). Later reserpine spike waves appeared almost continuously for about 8approximately12 hr during arousal and slow wave sleep stages. When the amplitude and grouping of spike waves became prominent, severe myoclonic jerky movements resembling \"pseudo hallucinatory\" behavior were observed. Polygrams of these periods were similar to those of PS except for abrupt arousal and orienting reactions. The onset of the typical PS episode was delayed by more than 8approximately9 hr. 2). Repeated doses of PCPA (500 mg/kg/day for 3 consecutive days, i.p.) caused only slight suppressive effect on slow wave sleep (SS), but spike waves similar to TR spike and/or reserpine spike waves developed throughout SS. When the amplitude and grouping of these spike waves were progressively increased, SS was often followed by PS. Abrupt enhancement of these spike waves as associated with \"pseudo hallucinatory\" behavior and aroused the animal. Usually these spike waves were not seen during arousal phase. When reserpine (0.5 mg/kg) was given i.v. to PCPA-treated rabbits, the latent period of appearance of reserpine spike waves was markedly shortened. 3) alpha-MMT, at a dose which had no effect on SS, markedly suppressed PS for a long period. These findings suggest that 5HT and NA in the lower brainstem play inhibitory roles on the triggering mechanism of PS.", "contents": "[Effects of monoamine-related compounds on the sleep-awake cycle in rabbits]. The role of 5HT and NA in the regulation of the sleep-awake cycle, especially in the triggering mechanisms of paradoxical sleep (PT), was studied in rabbits using reserpine, parachlorophenylalanine (PCPA), alpha-methyl-p-tyrosine (alpha-MT) and alpha-methyl -m-tyrosine (alpha-MMT). 1) Reserpine (0.5 mg/kg, i.v.) caused a diphasic action on the brain electrical activity in rabbits: an initial activation pattern in the EEG which continued to 2approximately3 hr, was followed gradually by a slow wave. Forty to sixty min after reserpine administration, spike waves resembling the PGO waves in cats appeared from the medial nucleus Trapezoides (Trap. m.) in rabbits. From the electrophysiological point of view, these spike waves (reserpine spike waves) were in many respects similar to those recorded during PS (TR spike waves). Later reserpine spike waves appeared almost continuously for about 8approximately12 hr during arousal and slow wave sleep stages. When the amplitude and grouping of spike waves became prominent, severe myoclonic jerky movements resembling \"pseudo hallucinatory\" behavior were observed. Polygrams of these periods were similar to those of PS except for abrupt arousal and orienting reactions. The onset of the typical PS episode was delayed by more than 8approximately9 hr. 2). Repeated doses of PCPA (500 mg/kg/day for 3 consecutive days, i.p.) caused only slight suppressive effect on slow wave sleep (SS), but spike waves similar to TR spike and/or reserpine spike waves developed throughout SS. When the amplitude and grouping of these spike waves were progressively increased, SS was often followed by PS. Abrupt enhancement of these spike waves as associated with \"pseudo hallucinatory\" behavior and aroused the animal. Usually these spike waves were not seen during arousal phase. When reserpine (0.5 mg/kg) was given i.v. to PCPA-treated rabbits, the latent period of appearance of reserpine spike waves was markedly shortened. 3) alpha-MMT, at a dose which had no effect on SS, markedly suppressed PS for a long period. These findings suggest that 5HT and NA in the lower brainstem play inhibitory roles on the triggering mechanism of PS."}
{"id": "PMID:185132", "title": "[Therapy of chronic non-specific respiratory tract diseases. 2. Therapy of infection, oxygen therapy, supplementary therapy].", "content": "Based on the pathological findings and functional analysis treatment of chronic non-specific lung disease (CNSLD) consists in improvement of secretion disorders and airways obstruction as well as in antiphlogistic treatment. The agents and drugs for therapy of pulmonary impairment are reviewed, the efficacy, way of administration, and side effects are outlined. Drug therapy is complemented by digitalis, oxygen administration, physical measures, and causative therapy. With these complex therapeutic efforts an effective therapy of chronic non-specific lung diseases is possible.", "contents": "[Therapy of chronic non-specific respiratory tract diseases. 2. Therapy of infection, oxygen therapy, supplementary therapy]. Based on the pathological findings and functional analysis treatment of chronic non-specific lung disease (CNSLD) consists in improvement of secretion disorders and airways obstruction as well as in antiphlogistic treatment. The agents and drugs for therapy of pulmonary impairment are reviewed, the efficacy, way of administration, and side effects are outlined. Drug therapy is complemented by digitalis, oxygen administration, physical measures, and causative therapy. With these complex therapeutic efforts an effective therapy of chronic non-specific lung diseases is possible."}
{"id": "PMID:185134", "title": "[Metabolism of nicotinic acid in plant cell suspension cultures, III: Formation and metabolism of trigonelline (author's transl)].", "content": "Cell suspension cultures of Phaseolus aureus, Glycinemax., Cicer arietinum and Chenopodium rubrum convert nicotinic acid and nicotinamide into N-methyl nicotinic acid (trigonelline). Application of [carboxyl-14C]- and [N-methyl-14C]nicotinic acid to cell cultures demonstrated that 1) the nicotinic acid moiety of trigonelline is funnelled into the pyridine nucleotide cycle, 2) trigonelline is demethylated partly oxidatively, but predominantly non-oxidatively, transferring the methyl carbon atom to still unknown acceptors, and 3) uptake of trigonelline by mung bean cell cultures is accompanied by demethylation and instantaneous remethylation reactions. Cell suspension cultures of parsley (Petroselinum hortense Hoffm.) show uptake but no metabolism of trigonelline. The data are compared with trigonelline metabolism in intact plants.", "contents": "[Metabolism of nicotinic acid in plant cell suspension cultures, III: Formation and metabolism of trigonelline (author's transl)]. Cell suspension cultures of Phaseolus aureus, Glycinemax., Cicer arietinum and Chenopodium rubrum convert nicotinic acid and nicotinamide into N-methyl nicotinic acid (trigonelline). Application of [carboxyl-14C]- and [N-methyl-14C]nicotinic acid to cell cultures demonstrated that 1) the nicotinic acid moiety of trigonelline is funnelled into the pyridine nucleotide cycle, 2) trigonelline is demethylated partly oxidatively, but predominantly non-oxidatively, transferring the methyl carbon atom to still unknown acceptors, and 3) uptake of trigonelline by mung bean cell cultures is accompanied by demethylation and instantaneous remethylation reactions. Cell suspension cultures of parsley (Petroselinum hortense Hoffm.) show uptake but no metabolism of trigonelline. The data are compared with trigonelline metabolism in intact plants."}
{"id": "PMID:185135", "title": "[Metabolism of nicotinic acid in plant cell suspension cultures, IV: Occurrence and metabolism of nicotinic acid N-alpha-arabinoside (author's transl)].", "content": "Application of nicotinic acid to cell suspension cultures of Petroselinum hortense Hoffm., Daucus carota, Nicotiana tabacum and Nicotiana glauca leads to the formation of the recently isolated[2] nicotinic acid N-alpha-L-arabinoside. In these cell cultures the arabinoside is a metabolically active compound; the nicotinic acid moiety is used for NAD synthesis and nicotinic acid degradation involving decarboxylation and ring fission. N-Methylnicotinic acid (trigonelline) and nicotinic acid N-alpha-L-arabinoside occur alternatively in plant cell suspension cultures, but seem to fulfil the same function as a reserve form for nicotinic acid. Catabolism of nicotinic acid in parsley cell suspension cultures does not involve 6-hydroxynicotinic acid as an intermediate.", "contents": "[Metabolism of nicotinic acid in plant cell suspension cultures, IV: Occurrence and metabolism of nicotinic acid N-alpha-arabinoside (author's transl)]. Application of nicotinic acid to cell suspension cultures of Petroselinum hortense Hoffm., Daucus carota, Nicotiana tabacum and Nicotiana glauca leads to the formation of the recently isolated[2] nicotinic acid N-alpha-L-arabinoside. In these cell cultures the arabinoside is a metabolically active compound; the nicotinic acid moiety is used for NAD synthesis and nicotinic acid degradation involving decarboxylation and ring fission. N-Methylnicotinic acid (trigonelline) and nicotinic acid N-alpha-L-arabinoside occur alternatively in plant cell suspension cultures, but seem to fulfil the same function as a reserve form for nicotinic acid. Catabolism of nicotinic acid in parsley cell suspension cultures does not involve 6-hydroxynicotinic acid as an intermediate."}
{"id": "PMID:185136", "title": "[Studies on cytochrome c oxidase, I. Purification and characterization of bovine myocardial enzyme and identification of peptide chains in the complex].", "content": "As part of the preliminary work for the structural elucidation of cytochrome c oxidase, the enzyme complex was isolated from bovine heart muscle and characterised chemically. The enzyme contains 10-11 nmol haem a, and 12-13 nmol copper per mg protein. The solubilised active enzyme also contains 5% phospholipid, comprising about 2 mol each of cardiolipin and phosphatidylethanolamine per mol haem a. In addition, the preparation contains a small number of detergent molecules (Tween-80). Eight polypeptide components were isolated by preparative dodecylsulphate gel electrophoresis, gel filtration on Biogel P-60, and counter current distribution. The apparent molecular weights of these components were I - 36 000, II - 28 000 (21 000), III - 19 000, IV - 14 000, V - 12 500, VI - 11 000, VII - 10 000 and VIII - 6000. At least seven intact polypeptide chains contribute to the structure of the enzyme complex of the terminal oxidase. On the basis of amino acid analysis and end group determination, they can be divided into two groups. The high molecular weight peptides I -III are hydrophobic and their amino acid compositions differ markedly from those of known enzyme proteins, especially with respect to their contents of leucine and methionine. Components I and II have formyl methionine at their N-termini. They are therefore possibly mitochondrial membrane components from complex 4 of the respiratory chain. Polypeptides IV - VII resemble functional enzyme subunits in their amino acid composition. Some of them possess free N-termini (alanine). The low molecular weight component VIII is heterogeneous and contains the N-terminal amino acids isoleucine, serine and phenylelanine in non-stoichiometric amounts. Analysis gives a minimal protein molecular weight of 130 000 (65 000 per haem a) for the two haem and two copper-containing \"monomers\". The molecular weight of the moiety preliminarily defined as enzymatic is about 48 000. The chemical characterisation provides data for the strategy of the subsequent sequence analysis of the polypeptides.", "contents": "[Studies on cytochrome c oxidase, I. Purification and characterization of bovine myocardial enzyme and identification of peptide chains in the complex]. As part of the preliminary work for the structural elucidation of cytochrome c oxidase, the enzyme complex was isolated from bovine heart muscle and characterised chemically. The enzyme contains 10-11 nmol haem a, and 12-13 nmol copper per mg protein. The solubilised active enzyme also contains 5% phospholipid, comprising about 2 mol each of cardiolipin and phosphatidylethanolamine per mol haem a. In addition, the preparation contains a small number of detergent molecules (Tween-80). Eight polypeptide components were isolated by preparative dodecylsulphate gel electrophoresis, gel filtration on Biogel P-60, and counter current distribution. The apparent molecular weights of these components were I - 36 000, II - 28 000 (21 000), III - 19 000, IV - 14 000, V - 12 500, VI - 11 000, VII - 10 000 and VIII - 6000. At least seven intact polypeptide chains contribute to the structure of the enzyme complex of the terminal oxidase. On the basis of amino acid analysis and end group determination, they can be divided into two groups. The high molecular weight peptides I -III are hydrophobic and their amino acid compositions differ markedly from those of known enzyme proteins, especially with respect to their contents of leucine and methionine. Components I and II have formyl methionine at their N-termini. They are therefore possibly mitochondrial membrane components from complex 4 of the respiratory chain. Polypeptides IV - VII resemble functional enzyme subunits in their amino acid composition. Some of them possess free N-termini (alanine). The low molecular weight component VIII is heterogeneous and contains the N-terminal amino acids isoleucine, serine and phenylelanine in non-stoichiometric amounts. Analysis gives a minimal protein molecular weight of 130 000 (65 000 per haem a) for the two haem and two copper-containing \"monomers\". The molecular weight of the moiety preliminarily defined as enzymatic is about 48 000. The chemical characterisation provides data for the strategy of the subsequent sequence analysis of the polypeptides."}
{"id": "PMID:185137", "title": "Chirality of the hydrogen transfer to the coenzyme catalyzed by ribitol dehydrogenase from Klebsiella pneumoniae and D-mannitol 1-phosphate dehydrogenase from Escherichia coli.", "content": "The stereochemistry of the hydrogen transfer to NAD catalyzed by ribitol dehydrogenase (ribitol:NAD 2-oxidoreductase, EC 1.1.1.56) from Klebsiella pneumoniae and D-mannitol-1-phosphate dehydrogenase (D-mannitol-1-phosphate:NAD 2-oxidoreductase, EC 1.1.1.17) from Escherichia coli was investigated. [4-3H]NAD was enzymatically reduced with nonlabelled ribitol in the presence of ribitol dehydrogenase and with nonlabelled D-mannitol 1-phosphate and D-mannitol 1-phosphate dehydrogenase, respectively. In both cases the [4-3H]-NADH produced was isolated and the chirality at the C-4 position determined. It was found that after the transfer of hydride, the label was in both reactions exclusively confined to the (4R) position of the newly formed [4-3H]NADH. In order to explain these results, the hydrogen transferred from the nonlabelled substrates to [4-3H]NAD must have entered the (4S) position of the nicotinamide ring. These data indicate for both investigated inducible dehydrogenases a classification as B or (S) type enzymes. Ribitol also can be dehydrogenated by the constitutive A-type L-iditol dehydrogenase (L-iditol:NAD 5-oxidoreductase, EC 1.1.1.14) from sheep liver. When L-iditol dehydrogenase utilizes ribitol as hydrogen donor, the same A-type classification for this oxidoreductase, as expected, holds true. For the first time, opposite chirality of hydrogen transfer to NAD in one organic reaction--ribitol + NAD = D-ribu + NADH + H--is observed when two different dehydrogenases, the inducible ribitol dehydrogenase from K. pneumoniae and the constitutive L-iditol dehydrogenase from sheep liver, are used as enzymes. This result contradicts the previous generalization that the chirality of hydrogen transfer to the coenzyme for the same reaction is independent of the source of the catalyzing enzyme.", "contents": "Chirality of the hydrogen transfer to the coenzyme catalyzed by ribitol dehydrogenase from Klebsiella pneumoniae and D-mannitol 1-phosphate dehydrogenase from Escherichia coli. The stereochemistry of the hydrogen transfer to NAD catalyzed by ribitol dehydrogenase (ribitol:NAD 2-oxidoreductase, EC 1.1.1.56) from Klebsiella pneumoniae and D-mannitol-1-phosphate dehydrogenase (D-mannitol-1-phosphate:NAD 2-oxidoreductase, EC 1.1.1.17) from Escherichia coli was investigated. [4-3H]NAD was enzymatically reduced with nonlabelled ribitol in the presence of ribitol dehydrogenase and with nonlabelled D-mannitol 1-phosphate and D-mannitol 1-phosphate dehydrogenase, respectively. In both cases the [4-3H]-NADH produced was isolated and the chirality at the C-4 position determined. It was found that after the transfer of hydride, the label was in both reactions exclusively confined to the (4R) position of the newly formed [4-3H]NADH. In order to explain these results, the hydrogen transferred from the nonlabelled substrates to [4-3H]NAD must have entered the (4S) position of the nicotinamide ring. These data indicate for both investigated inducible dehydrogenases a classification as B or (S) type enzymes. Ribitol also can be dehydrogenated by the constitutive A-type L-iditol dehydrogenase (L-iditol:NAD 5-oxidoreductase, EC 1.1.1.14) from sheep liver. When L-iditol dehydrogenase utilizes ribitol as hydrogen donor, the same A-type classification for this oxidoreductase, as expected, holds true. For the first time, opposite chirality of hydrogen transfer to NAD in one organic reaction--ribitol + NAD = D-ribu + NADH + H--is observed when two different dehydrogenases, the inducible ribitol dehydrogenase from K. pneumoniae and the constitutive L-iditol dehydrogenase from sheep liver, are used as enzymes. This result contradicts the previous generalization that the chirality of hydrogen transfer to the coenzyme for the same reaction is independent of the source of the catalyzing enzyme."}
{"id": "PMID:185138", "title": "Legal issues in the treatment of adolescent psychiatric inpatients.", "content": "When planning a specialized adolescent treatment unit for a regional state mental hospital in North Carolina, staff of the child psychiatry training program explored several critical legal issues surrounding the admission, treatment, and discharge of minors, as well as issues of confidentiality. Through a question-and-answer format they conclude that, to help avoid conditions that could result in successful litigation against the hospital, parents, adolescents, and staff must have a documented, mutual agreement to and understanding of the techniques, procedures, and limitations of the treatment program. Such documentation could be provided through a signed treatment contract.", "contents": "Legal issues in the treatment of adolescent psychiatric inpatients. When planning a specialized adolescent treatment unit for a regional state mental hospital in North Carolina, staff of the child psychiatry training program explored several critical legal issues surrounding the admission, treatment, and discharge of minors, as well as issues of confidentiality. Through a question-and-answer format they conclude that, to help avoid conditions that could result in successful litigation against the hospital, parents, adolescents, and staff must have a documented, mutual agreement to and understanding of the techniques, procedures, and limitations of the treatment program. Such documentation could be provided through a signed treatment contract."}
{"id": "PMID:185140", "title": "Primary hyperlipoproteinaemia in a Danish family.", "content": "A Danish family consisting of 80 persons, 72 between the ages of 3 and 70 years, was examined for the presence of primary hyperlipoproteinaemia (HLP), resulting in the finding of types II A (8 cases), II B (4 cases), III (2 cases), IV (5 cases), and V (2 cases). The pedigree of the family is presented together with lipid data and HLP type. Five cases of the so-called 'sinking pre-beta midband', which can often be correlated to ischaemic heart disease, have been found using polyacrylamide gel electrophoresis (PGE); two of these subjects had arteriosclerotic disease, one had uratic arthritis, while the other two were normal. A comparative evaluation of the results of electrophoresis should be considered of greater importance when studying families, rather than individual persons, inasmuch as intra-familial lipid patterns appear to occur with a positive correlation to at least serum cholesterol. Continued observation will probably reveal a lipid abnormality characteristic for the family even though according to the reference material available it must be considered as normal.", "contents": "Primary hyperlipoproteinaemia in a Danish family. A Danish family consisting of 80 persons, 72 between the ages of 3 and 70 years, was examined for the presence of primary hyperlipoproteinaemia (HLP), resulting in the finding of types II A (8 cases), II B (4 cases), III (2 cases), IV (5 cases), and V (2 cases). The pedigree of the family is presented together with lipid data and HLP type. Five cases of the so-called 'sinking pre-beta midband', which can often be correlated to ischaemic heart disease, have been found using polyacrylamide gel electrophoresis (PGE); two of these subjects had arteriosclerotic disease, one had uratic arthritis, while the other two were normal. A comparative evaluation of the results of electrophoresis should be considered of greater importance when studying families, rather than individual persons, inasmuch as intra-familial lipid patterns appear to occur with a positive correlation to at least serum cholesterol. Continued observation will probably reveal a lipid abnormality characteristic for the family even though according to the reference material available it must be considered as normal."}
{"id": "PMID:185144", "title": "C1 and human platelets. III. Role of C1 subcomponents in platelet aggregation induced by aggregated IgG.", "content": "Studies have been performed with platelets using C1 haemolytic assays and platelet aggregation induced by anti-C1q, anti-C1s and aggregated IgG in the presence of C1 subcomponents C1q, C1r and C1s. C1q was removed by EDTA or modified by collagenase from human platelets while after the same treatment C1s remained bound to the platelets. EDTA treated platelets were no longer aggregated by aggregated IgG. The addition of C1q restored the reactivity of the platelets to aggregated IgG while the addition of C1r or C1s was without effect. Furthermore, the addition of C1r or C1s to C1q inhibited the action of C1q in platelet aggregation induced by IgG.The possible association between the different C1 subcomponents and human platelets is discussed.", "contents": "C1 and human platelets. III. Role of C1 subcomponents in platelet aggregation induced by aggregated IgG. Studies have been performed with platelets using C1 haemolytic assays and platelet aggregation induced by anti-C1q, anti-C1s and aggregated IgG in the presence of C1 subcomponents C1q, C1r and C1s. C1q was removed by EDTA or modified by collagenase from human platelets while after the same treatment C1s remained bound to the platelets. EDTA treated platelets were no longer aggregated by aggregated IgG. The addition of C1q restored the reactivity of the platelets to aggregated IgG while the addition of C1r or C1s was without effect. Furthermore, the addition of C1r or C1s to C1q inhibited the action of C1q in platelet aggregation induced by IgG.The possible association between the different C1 subcomponents and human platelets is discussed."}
{"id": "PMID:185148", "title": "Mechanism of fever induction in rabbits.", "content": "Three exogenous pyrogens (Escherichia coli lipopolysaccharide, synthetic double-stranded ribonucleic acid. Newcastle disease virus) were compared with respect to their mechanisms of fever induction in rabbits. All inducers stimulated the production of an endogenous pyrogen demonstrated in the blood as well as prostaglandins of the E group, and of cyclic adenosine 3',5'-monophosphate in the cerebrospinal fluid. The concentrations of these compounds were elevated approximately twofold as compared to the controls. Independently of the mode of induction, the fever reaction could be prevented by pretreatment with 5 mg of cycloheximide per kg, although the three fever mediators were induced as in febrile animals. Consequently, at least one additional fever mediator that is sensitive to a 30 to 50% inhibition of protein synthesis by cycloheximide has to be postulated. The comparable reactions of the rabbits after administration of different pyrogens argues for a similar fever mechanism. In contrast to fever induction there was no stimulation of endogenous pyrogen, prostaglandins of the E group, and cyclic adenosine 3',5'-monophosphate in hyperthermia as a consequence of exposure of the animals to exogenous overheating. Furthermore, hyperthermia could not be prevented by cycloheximide.", "contents": "Mechanism of fever induction in rabbits. Three exogenous pyrogens (Escherichia coli lipopolysaccharide, synthetic double-stranded ribonucleic acid. Newcastle disease virus) were compared with respect to their mechanisms of fever induction in rabbits. All inducers stimulated the production of an endogenous pyrogen demonstrated in the blood as well as prostaglandins of the E group, and of cyclic adenosine 3',5'-monophosphate in the cerebrospinal fluid. The concentrations of these compounds were elevated approximately twofold as compared to the controls. Independently of the mode of induction, the fever reaction could be prevented by pretreatment with 5 mg of cycloheximide per kg, although the three fever mediators were induced as in febrile animals. Consequently, at least one additional fever mediator that is sensitive to a 30 to 50% inhibition of protein synthesis by cycloheximide has to be postulated. The comparable reactions of the rabbits after administration of different pyrogens argues for a similar fever mechanism. In contrast to fever induction there was no stimulation of endogenous pyrogen, prostaglandins of the E group, and cyclic adenosine 3',5'-monophosphate in hyperthermia as a consequence of exposure of the animals to exogenous overheating. Furthermore, hyperthermia could not be prevented by cycloheximide."}
{"id": "PMID:185149", "title": "The Syrian hamster: a reproducible model for studying changes in intestinal fluid secretion in response to enterotoxin challenge.", "content": "Syrian hamsters respond in a predictable and reproducible manner to intragastric administration of purified cholera enterotoxin by intraluminal accumulation of fluid in the small bowel, cecum, and proximal colon. In the majority of animals this process is self limiting, and recovery occurs with full reabsorption of intestinal fluid by 30 to 35 h. The secretory response to 75 mug of cholera toxin has been defined, and the model was utilized to study the inhibitory effects of indomethacin, polymyxin B sulfate, glucose electrolyte solutions, and colchicine. These studies demonstrate its potential usefulness as a convenient and inexpensive technique for evaluation of pharmacological agents that might inhibit intestinal fluid secretion.", "contents": "The Syrian hamster: a reproducible model for studying changes in intestinal fluid secretion in response to enterotoxin challenge. Syrian hamsters respond in a predictable and reproducible manner to intragastric administration of purified cholera enterotoxin by intraluminal accumulation of fluid in the small bowel, cecum, and proximal colon. In the majority of animals this process is self limiting, and recovery occurs with full reabsorption of intestinal fluid by 30 to 35 h. The secretory response to 75 mug of cholera toxin has been defined, and the model was utilized to study the inhibitory effects of indomethacin, polymyxin B sulfate, glucose electrolyte solutions, and colchicine. These studies demonstrate its potential usefulness as a convenient and inexpensive technique for evaluation of pharmacological agents that might inhibit intestinal fluid secretion."}
{"id": "PMID:185150", "title": "Viral spread in the presence of neutralizing antibody: mechanisms of persistence in foamy virus infection.", "content": "Several viruses were categorized on the basis of their ability to spread from cell to contiguous cell and form plaques in the presence of antiviral antibody. Herpes simplex virus, cytomegalovirus, and vaccinia, measles, and foamy viruses were able to spread in the presence of neutralizing antibody, whereas coxsackievirus, encephalomyocarditis virus, vesicular stomatitis virus, mumps virus, and simian virus 5 failed to spread. A detailed study of one of these virus groups (simian foamy viruses) suggested that the ability of these viruses to spread from cell to cell in the presence of antiviral antibody, the failure of antiviral antibody and complement to lyse infected cells, and the poor induction and relative resistance of these viruses to the antiviral action of interferon contribute to the persistent nature of this infection.", "contents": "Viral spread in the presence of neutralizing antibody: mechanisms of persistence in foamy virus infection. Several viruses were categorized on the basis of their ability to spread from cell to contiguous cell and form plaques in the presence of antiviral antibody. Herpes simplex virus, cytomegalovirus, and vaccinia, measles, and foamy viruses were able to spread in the presence of neutralizing antibody, whereas coxsackievirus, encephalomyocarditis virus, vesicular stomatitis virus, mumps virus, and simian virus 5 failed to spread. A detailed study of one of these virus groups (simian foamy viruses) suggested that the ability of these viruses to spread from cell to cell in the presence of antiviral antibody, the failure of antiviral antibody and complement to lyse infected cells, and the poor induction and relative resistance of these viruses to the antiviral action of interferon contribute to the persistent nature of this infection."}
{"id": "PMID:185151", "title": "Antisera to human cytomegalovirus produced in hamsters: reactivity in radioimmunoassay and other antibody assay systems.", "content": "Hamsters immunized with human cytomegalovirus (CMV) concentrated and purified by polyethylene glycol precipitation and density gradient centrifugation produced antisera with high titers of specific viral antibody, and which showed no significant reactivity with human host cell components. The antisera had high titers of CMV antibody in complement fixation, indirect fluorescent-antibody (FA), and neutralization tests, but titers obtained by indirect radioimmunoassay (RIA) were markedly higher. The antisera were used to follow the development of CMV antigen in infected host cells by indirect RIA and indirect FA staining. Virus-specific antigen was first detectable by RIA at 8 h after infection, and by FA staining at 16 h; cells contained optimal amounts of antigen for RIA and FA assays at 72 to 100 h postinfection. Immune globulins from the antisera were labeled with 125I for use in direct RIA. The labeled globulins gave highly specific reactions with CMV-infected cells, including those infected with low-passage isolates, and showed no reactivity with cells infected with other human herpesviruses or certain other human viruses.", "contents": "Antisera to human cytomegalovirus produced in hamsters: reactivity in radioimmunoassay and other antibody assay systems. Hamsters immunized with human cytomegalovirus (CMV) concentrated and purified by polyethylene glycol precipitation and density gradient centrifugation produced antisera with high titers of specific viral antibody, and which showed no significant reactivity with human host cell components. The antisera had high titers of CMV antibody in complement fixation, indirect fluorescent-antibody (FA), and neutralization tests, but titers obtained by indirect radioimmunoassay (RIA) were markedly higher. The antisera were used to follow the development of CMV antigen in infected host cells by indirect RIA and indirect FA staining. Virus-specific antigen was first detectable by RIA at 8 h after infection, and by FA staining at 16 h; cells contained optimal amounts of antigen for RIA and FA assays at 72 to 100 h postinfection. Immune globulins from the antisera were labeled with 125I for use in direct RIA. The labeled globulins gave highly specific reactions with CMV-infected cells, including those infected with low-passage isolates, and showed no reactivity with cells infected with other human herpesviruses or certain other human viruses."}
{"id": "PMID:185152", "title": "Intrauterine transmission of Sendai virus in inbred mouse strains.", "content": "A study of Sendai virus infection in adult mice (2 to 3 months of age) showed that the inbred strains were more susceptible to infection than randomly bred Swiss white mice and that virus could be isolated from inbred strains for as long as 21 days postinfection. For this reason, these mouse strains (C57B1/6J [black] and C57Br [brown]) were selected for the study of intrauterine transmission of virus. The major effect of infection was a decreased weight of both embryos at 16 days of gestation and newborn mice. Virus was isolated from 17 to 20% of the embryos and at least 20 to 30% of the newborns from intravenously infected mothers. Fluorescent-antibody studies showed that the virus was widely distributed in the tissues of both embryos and newborns, including the central nervous system.", "contents": "Intrauterine transmission of Sendai virus in inbred mouse strains. A study of Sendai virus infection in adult mice (2 to 3 months of age) showed that the inbred strains were more susceptible to infection than randomly bred Swiss white mice and that virus could be isolated from inbred strains for as long as 21 days postinfection. For this reason, these mouse strains (C57B1/6J [black] and C57Br [brown]) were selected for the study of intrauterine transmission of virus. The major effect of infection was a decreased weight of both embryos at 16 days of gestation and newborn mice. Virus was isolated from 17 to 20% of the embryos and at least 20 to 30% of the newborns from intravenously infected mothers. Fluorescent-antibody studies showed that the virus was widely distributed in the tissues of both embryos and newborns, including the central nervous system."}
{"id": "PMID:185153", "title": "Central nervous system involvement in infectious mononucleosis with studies for Epstein-Barr virus.", "content": "Neurologic complications in three girls, aged four, fourteen and fifteen years, with infectious mononucleosis are reported. All three patients had meningoencephalitis, in two of them cerebellar involvement predominated, while the third patient had cerebral involvement with paresis of cerebral nerves. The diagnosis of an Epstein-Barr virus infection was established serologiccally and in the first patient also by the detection of the Epstein-Barr virus.", "contents": "Central nervous system involvement in infectious mononucleosis with studies for Epstein-Barr virus. Neurologic complications in three girls, aged four, fourteen and fifteen years, with infectious mononucleosis are reported. All three patients had meningoencephalitis, in two of them cerebellar involvement predominated, while the third patient had cerebral involvement with paresis of cerebral nerves. The diagnosis of an Epstein-Barr virus infection was established serologiccally and in the first patient also by the detection of the Epstein-Barr virus."}
{"id": "PMID:185154", "title": "[Mouse cytomegalovirus infection under cytosine arabinoside treatment].", "content": "The antiviral activity of cytosine arabinoside (ARA-C) against the mouse cytomegalovirus was investigated in animal experiments using various dosages. The substance did not exhibit any virostatic effect, but on the contrary fostered the viral infection. The virus concentration in the liver after administration of five dosages of 30 mg/kg of cytosine arabinoside was 35 times higher than that in untreated animals, and after five dosages of 45 mg/kg was 70 times higher. In addition the mortality rate for infected animals treated with cytosine arabinoside was significantly higher in relation to dosage. Cytosine arabinoside also acts as an immunosuppressor in humans. Adverse effects in cytomegalo-infection can therefore not be excluded. The use of cytosine arabinoside in therapy would thus appear to be highly questionable.", "contents": "[Mouse cytomegalovirus infection under cytosine arabinoside treatment]. The antiviral activity of cytosine arabinoside (ARA-C) against the mouse cytomegalovirus was investigated in animal experiments using various dosages. The substance did not exhibit any virostatic effect, but on the contrary fostered the viral infection. The virus concentration in the liver after administration of five dosages of 30 mg/kg of cytosine arabinoside was 35 times higher than that in untreated animals, and after five dosages of 45 mg/kg was 70 times higher. In addition the mortality rate for infected animals treated with cytosine arabinoside was significantly higher in relation to dosage. Cytosine arabinoside also acts as an immunosuppressor in humans. Adverse effects in cytomegalo-infection can therefore not be excluded. The use of cytosine arabinoside in therapy would thus appear to be highly questionable."}
{"id": "PMID:185157", "title": "Surface glycoproteins and concanavalin-A-mediated agglutinability of clonal variants and tumour cells derived from SV40-virus-transformed mouse 3T3 cells.", "content": "Cell strains isolated from an established line of SV40-transformed mouse 3T3 cells (SV3T3) showed large variations in the various parameters of transformation, viz. saturation density, serum requirement, contact inhibition of movement and of growth and Concanavalin-A-mediated agglutinability. These cell strains were studied for changes in elution profiles of fucose-labelled surface glycoproteins, using actively growing, untransformed 3T3 cells as controls. A cell strain established from a tumour arising after injection of wild-type SV3T3 cells and SV3T3 cells grown in vivo in diffusion chambers, was similarly studied. Changes in surface glycoproteins were observed only in the tumour-derived cell strain. The results suggest that alterations in surface glycoproteins are associated with the tumorigenic potential of the cells rather than with the transformed phenotype per se.", "contents": "Surface glycoproteins and concanavalin-A-mediated agglutinability of clonal variants and tumour cells derived from SV40-virus-transformed mouse 3T3 cells. Cell strains isolated from an established line of SV40-transformed mouse 3T3 cells (SV3T3) showed large variations in the various parameters of transformation, viz. saturation density, serum requirement, contact inhibition of movement and of growth and Concanavalin-A-mediated agglutinability. These cell strains were studied for changes in elution profiles of fucose-labelled surface glycoproteins, using actively growing, untransformed 3T3 cells as controls. A cell strain established from a tumour arising after injection of wild-type SV3T3 cells and SV3T3 cells grown in vivo in diffusion chambers, was similarly studied. Changes in surface glycoproteins were observed only in the tumour-derived cell strain. The results suggest that alterations in surface glycoproteins are associated with the tumorigenic potential of the cells rather than with the transformed phenotype per se."}
{"id": "PMID:185158", "title": "Neoplastic transformation of rat embryo cells with herpes simplex virus.", "content": "Sprague Dawley rat embryo cells (REF) were transformed by inoculation with herpes simplex virus (HSV) and incubation at 42 degrees C for 8 days. The infected cultures were subsequently returned to 37 degrees C and two types of cell clone were isolated from foci of growing cells after 4 weeks. One of the clones consisted of epithelial-like cells and did not produce HSV (REF-Tep-NP). The second consisted of spindle-shaped cells and cultures of these cells persistently developed small areas of degeneration where production of infectious HSV (REF-Tsp-P) took place. An additional clone which did not produce any more HSV (REF-Tsp-NP) was isolated from REF-Tsp-P in the presence of HSV-antiserum. REF-Tsp-P and REF-Tsp-NP grew more rapidly than REF and also formed foci in soft agar. REF-Tep-NP had a growth rate between that of normal rat embryo cells and that of both REF-Tsp-NP and REF-Tsp-P and did not form foci in soft agar. REF-Tsp-NP cells, in contrast to REF-Tep-NP cells, were resistant to superinfection with HSV types 1 and 2. REF-Tsp-P and REF-Tsp-NP produced metastasizing sarcomas in rats. After inoculation of 10(3) REF-Tsp-NP cells into 1-day-old rats tumours developed rapidly. REF-Tep-NP cells did not induce tumours in rats. The parental REF cells produced no tumours, even when 10(8) cells were inoculated into the rats. Positive immunofluorescence was observed in all three transformed cells only with the hyperimmune rabbit sera but not with human anti-HSV reconvalescence immune sera.", "contents": "Neoplastic transformation of rat embryo cells with herpes simplex virus. Sprague Dawley rat embryo cells (REF) were transformed by inoculation with herpes simplex virus (HSV) and incubation at 42 degrees C for 8 days. The infected cultures were subsequently returned to 37 degrees C and two types of cell clone were isolated from foci of growing cells after 4 weeks. One of the clones consisted of epithelial-like cells and did not produce HSV (REF-Tep-NP). The second consisted of spindle-shaped cells and cultures of these cells persistently developed small areas of degeneration where production of infectious HSV (REF-Tsp-P) took place. An additional clone which did not produce any more HSV (REF-Tsp-NP) was isolated from REF-Tsp-P in the presence of HSV-antiserum. REF-Tsp-P and REF-Tsp-NP grew more rapidly than REF and also formed foci in soft agar. REF-Tep-NP had a growth rate between that of normal rat embryo cells and that of both REF-Tsp-NP and REF-Tsp-P and did not form foci in soft agar. REF-Tsp-NP cells, in contrast to REF-Tep-NP cells, were resistant to superinfection with HSV types 1 and 2. REF-Tsp-P and REF-Tsp-NP produced metastasizing sarcomas in rats. After inoculation of 10(3) REF-Tsp-NP cells into 1-day-old rats tumours developed rapidly. REF-Tep-NP cells did not induce tumours in rats. The parental REF cells produced no tumours, even when 10(8) cells were inoculated into the rats. Positive immunofluorescence was observed in all three transformed cells only with the hyperimmune rabbit sera but not with human anti-HSV reconvalescence immune sera."}
{"id": "PMID:185159", "title": "Markers to distinguish normal and neoplastic mammary epithelial cells in vitro: comparison of saturation density, morphology and concanavalin A reactivity.", "content": "Normal and premalignant mouse mammary epithelial cells can be prepared in high yields by collagenase dissociation of minced glands followed by a brief, differential centrifugation to remove contaminating fibroblasts and fat cells. The major difficulties in preparing pure cultures in quantity are 1) incomplete dissociation of gland material, and 2) cell death during enzymatic digestion. These problems are eliminated by careful selection of collagenases for dissociation. Normal and premalignant mammary epithelial cells are morphologically indistinguishable from malignant mouse mammary epithelial cells in primary monolayer cultures. In addition, the growth rates and saturation densities achieved by normal mammary epithelial cells are indistinguishable from those of malignant mammary epithelial cells in primary culture. In both cases, a monolayer of cells is preserved with no evidence of focal overgrowth. Malignant adenocarcinoma mammary cells can however be distinguished from normal mammary epithelial cells by virtue of differences in their surface interactions with concanavalin A. A hemadsorption assay using Con-A-coated erythrocytes was the most sensitive indicator for these differences. In hemadsorption assays malignant mammary epithelial cells were half-maximally reactive with 2.5 mug/ml concanavalin A, while normal cells were completely unreactive even at concanavalin A concentrations five-times higher. Premalignant mammary epithelial cells were as reactive as malignant mammary epithelial cells in the hemadsorption assays. Hemadsorption of malignant cells was observed in primary and secondary cultures of epithelium as well as in cell lines. Malignant cells forming mammary adenocarcinomas were as highly reactive as malignant cells forming scirrhous carcinomas. Malignant cells not releasing mammary tumor virus (MuMTV) were as reactive as cells releasing that virus. Adsorption of concanavalin-A-coated erythrocytes to normal mammary epithelial cells could be induced by brief treatment of cell monolayers with hyaluronidase. Exposure of active sites was not affected with either trypsin or collagenase. Our results show that while the growth of malignant cells does not serve to distinguish them from normal cells in monolayer culture, surface changes do exist which can be identified by differences in concanavalin A reactivity. Since the earliest transformants identifiable in vivo (premalignant) have undergone conversion of the surface marker, concanavalin-A-mediated hemadsorption provides a sensitive measure for mammary epithelial cell transformants in vitro.", "contents": "Markers to distinguish normal and neoplastic mammary epithelial cells in vitro: comparison of saturation density, morphology and concanavalin A reactivity. Normal and premalignant mouse mammary epithelial cells can be prepared in high yields by collagenase dissociation of minced glands followed by a brief, differential centrifugation to remove contaminating fibroblasts and fat cells. The major difficulties in preparing pure cultures in quantity are 1) incomplete dissociation of gland material, and 2) cell death during enzymatic digestion. These problems are eliminated by careful selection of collagenases for dissociation. Normal and premalignant mammary epithelial cells are morphologically indistinguishable from malignant mouse mammary epithelial cells in primary monolayer cultures. In addition, the growth rates and saturation densities achieved by normal mammary epithelial cells are indistinguishable from those of malignant mammary epithelial cells in primary culture. In both cases, a monolayer of cells is preserved with no evidence of focal overgrowth. Malignant adenocarcinoma mammary cells can however be distinguished from normal mammary epithelial cells by virtue of differences in their surface interactions with concanavalin A. A hemadsorption assay using Con-A-coated erythrocytes was the most sensitive indicator for these differences. In hemadsorption assays malignant mammary epithelial cells were half-maximally reactive with 2.5 mug/ml concanavalin A, while normal cells were completely unreactive even at concanavalin A concentrations five-times higher. Premalignant mammary epithelial cells were as reactive as malignant mammary epithelial cells in the hemadsorption assays. Hemadsorption of malignant cells was observed in primary and secondary cultures of epithelium as well as in cell lines. Malignant cells forming mammary adenocarcinomas were as highly reactive as malignant cells forming scirrhous carcinomas. Malignant cells not releasing mammary tumor virus (MuMTV) were as reactive as cells releasing that virus. Adsorption of concanavalin-A-coated erythrocytes to normal mammary epithelial cells could be induced by brief treatment of cell monolayers with hyaluronidase. Exposure of active sites was not affected with either trypsin or collagenase. Our results show that while the growth of malignant cells does not serve to distinguish them from normal cells in monolayer culture, surface changes do exist which can be identified by differences in concanavalin A reactivity. Since the earliest transformants identifiable in vivo (premalignant) have undergone conversion of the surface marker, concanavalin-A-mediated hemadsorption provides a sensitive measure for mammary epithelial cell transformants in vitro."}
{"id": "PMID:185160", "title": "Cell surface changes observed in MC-29 virus-infected chicken-embryo fibroblast (CEC) cultures.", "content": "By transmission and scanning electron microscopic studies of MC-29 virus-infected CEC cultures, C-type virus particles were detected in the medium of infected cultures, in infected cells and in intracellular vacuoles. Virus budding was also observed. In the scanning electron microscope (SEM) so-called blebs appeared on the surfaces of the infected cells, in a number proportional to the concentration of the virus preparation. On the basis of the size of the blebs, it could be considered that virus formation was taking place in their center. In control cells, neither viruses nor blebs were observed. This method will presumably be suitable for the titration of virus preparations.", "contents": "Cell surface changes observed in MC-29 virus-infected chicken-embryo fibroblast (CEC) cultures. By transmission and scanning electron microscopic studies of MC-29 virus-infected CEC cultures, C-type virus particles were detected in the medium of infected cultures, in infected cells and in intracellular vacuoles. Virus budding was also observed. In the scanning electron microscope (SEM) so-called blebs appeared on the surfaces of the infected cells, in a number proportional to the concentration of the virus preparation. On the basis of the size of the blebs, it could be considered that virus formation was taking place in their center. In control cells, neither viruses nor blebs were observed. This method will presumably be suitable for the titration of virus preparations."}
{"id": "PMID:185161", "title": "Changes in cellularity induced by radiation in a solid tumour.", "content": "The growth, and cellular responses of Morris hepatoma 3924 A to a locally-administered dose of 3750 R X-rays were studied using the following parameters; (1) relative tumour volume changes; (2) tritiated thymidine (3H-TdR) incorporation into DNA; (3) tumour DNA content and (4) cellular analysis, including 3H-TdR labelling index, mitotic index, aberrant mitotic frequency and relative cell density. Before depression of tumour growth, cell proliferation is temporarily interuppted. As proliferation is reinitiated, a short-lived synhcrony and prolongation of cell-cycle traverse are reflected in (a) the labelling index and mitotic index, (b) the relative cell density, and (c) the rate of incorporation of 3H-TdR into DNA. Within 4 days after radiation, cell proliferation and 3H-TdR incorporation are significantly depressed. Simultaneously there are reductions in both the relative cell density and tumour DNA contents, and these remain depressed as the tumours initiate regression. From these studies, it is apparent that the cellular responses to radiation insult occur well in advance of measurable volume changes and are observed both in tumours that continue to regress and in those that initiate regrowth.", "contents": "Changes in cellularity induced by radiation in a solid tumour. The growth, and cellular responses of Morris hepatoma 3924 A to a locally-administered dose of 3750 R X-rays were studied using the following parameters; (1) relative tumour volume changes; (2) tritiated thymidine (3H-TdR) incorporation into DNA; (3) tumour DNA content and (4) cellular analysis, including 3H-TdR labelling index, mitotic index, aberrant mitotic frequency and relative cell density. Before depression of tumour growth, cell proliferation is temporarily interuppted. As proliferation is reinitiated, a short-lived synhcrony and prolongation of cell-cycle traverse are reflected in (a) the labelling index and mitotic index, (b) the relative cell density, and (c) the rate of incorporation of 3H-TdR into DNA. Within 4 days after radiation, cell proliferation and 3H-TdR incorporation are significantly depressed. Simultaneously there are reductions in both the relative cell density and tumour DNA contents, and these remain depressed as the tumours initiate regression. From these studies, it is apparent that the cellular responses to radiation insult occur well in advance of measurable volume changes and are observed both in tumours that continue to regress and in those that initiate regrowth."}
{"id": "PMID:185162", "title": "Free radical inactivation of lactate dehydrogenase.", "content": "The enzyme lactate dehydrogenase (LDH) has been irradiated under various conditions to assess the relative contributions of -H, -OH, H2O2 and -O2- to LDH inactivation, and it is concluded that -OH is the only important inactivating species. Further the effect of the selective free radicals, -(SCN)2-, -Br2- and -I2- on the activity has been studied. In neutral solution, the order of inactivating effectiveness is -I2- greater than -OH greater than -Br2- greater than -(SCN)2-. At pH 8-6, -OH and -Br2- are approximately equal in effectiveness, whereas -(SCN)2- is the least efficient. The radiation inactivation of LDH is accompanied by a loss of sulphydryl groups, and it is suggested that the primary target for radiation damage in LDH is the active site cysteine-165. Subsequent conformational changes are suggested to account for the apparent loss of coenzyme-binding ability and changes in the enzyme's kinetic parameters. The effect of bound coenzyme (NAD) on radiation-induced inactivation of N2O and air-saturated solutions was also investigated, and it is shown that NAD binding protects LDH.", "contents": "Free radical inactivation of lactate dehydrogenase. The enzyme lactate dehydrogenase (LDH) has been irradiated under various conditions to assess the relative contributions of -H, -OH, H2O2 and -O2- to LDH inactivation, and it is concluded that -OH is the only important inactivating species. Further the effect of the selective free radicals, -(SCN)2-, -Br2- and -I2- on the activity has been studied. In neutral solution, the order of inactivating effectiveness is -I2- greater than -OH greater than -Br2- greater than -(SCN)2-. At pH 8-6, -OH and -Br2- are approximately equal in effectiveness, whereas -(SCN)2- is the least efficient. The radiation inactivation of LDH is accompanied by a loss of sulphydryl groups, and it is suggested that the primary target for radiation damage in LDH is the active site cysteine-165. Subsequent conformational changes are suggested to account for the apparent loss of coenzyme-binding ability and changes in the enzyme's kinetic parameters. The effect of bound coenzyme (NAD) on radiation-induced inactivation of N2O and air-saturated solutions was also investigated, and it is shown that NAD binding protects LDH."}
{"id": "PMID:185163", "title": "Effects of X-irradiation on the hybridization of rat thymus nuclear RNA with repeated and unique DNA sequences.", "content": "The kinetics of DNA hybridization with heterogeneous nuclear RNA (hnRNA) from normal and phytohaemagglutinin (PHA)-stimulated thymocytes has been studied in control rats and in animals 30 min after exposure to whole-body X-radiation with 400 rad. Irradiation results in a diminished ability of hnRNA to form hybrids with DNA at all C0t values ranging from 10(-3) to 10(4). Since this effect is most pronounced in the regions of low repetitive and unique DNA sequences, it is concluded that whole-body X-irradiation of animals may also suppress the transcription, particularly, in these regions.", "contents": "Effects of X-irradiation on the hybridization of rat thymus nuclear RNA with repeated and unique DNA sequences. The kinetics of DNA hybridization with heterogeneous nuclear RNA (hnRNA) from normal and phytohaemagglutinin (PHA)-stimulated thymocytes has been studied in control rats and in animals 30 min after exposure to whole-body X-radiation with 400 rad. Irradiation results in a diminished ability of hnRNA to form hybrids with DNA at all C0t values ranging from 10(-3) to 10(4). Since this effect is most pronounced in the regions of low repetitive and unique DNA sequences, it is concluded that whole-body X-irradiation of animals may also suppress the transcription, particularly, in these regions."}
{"id": "PMID:185164", "title": "E.s.r. of spin-trapped radicals in gamma-irradiated aqueous solutions of nucleic acids and their constituents.", "content": "The gamma-radiolysis of de-aerated neutral aqueous solutions of uracil, thymine, cytosine and of the corresponding nucleosides and nucleotides and of calf-thymus DNA was investigated. For uracil and thymine, the U.V. photolysis of aqueous solutions containing H2O2 was also studied. The short-lived radicals were spin-trapped by tert-nitrosobutane and identified by electron-spin-resonance spectroscopy. For all compounds two or more radicals were observed, and these could be distinguished by following the thermal decay of the spin adducts. Radicals formed by the addition of H or OH at the C(5) or C(6) positions of the pyrimidine derivatives were observed in all cases. Sodium formate was used as a scavenger for H and OH to identify the radicals formed by eaq-. Spin-trapped radicals in gamma-irradiated aqueous solutions of polynucleotides exhibited broad e.s.r. lines. For DNA gel, additional narrow lines due to scission products were also found.", "contents": "E.s.r. of spin-trapped radicals in gamma-irradiated aqueous solutions of nucleic acids and their constituents. The gamma-radiolysis of de-aerated neutral aqueous solutions of uracil, thymine, cytosine and of the corresponding nucleosides and nucleotides and of calf-thymus DNA was investigated. For uracil and thymine, the U.V. photolysis of aqueous solutions containing H2O2 was also studied. The short-lived radicals were spin-trapped by tert-nitrosobutane and identified by electron-spin-resonance spectroscopy. For all compounds two or more radicals were observed, and these could be distinguished by following the thermal decay of the spin adducts. Radicals formed by the addition of H or OH at the C(5) or C(6) positions of the pyrimidine derivatives were observed in all cases. Sodium formate was used as a scavenger for H and OH to identify the radicals formed by eaq-. Spin-trapped radicals in gamma-irradiated aqueous solutions of polynucleotides exhibited broad e.s.r. lines. For DNA gel, additional narrow lines due to scission products were also found."}
{"id": "PMID:185181", "title": "Acoustic reflex latency as a function of frequency and intensity of eliciting stimulus.", "content": "The purpose of the present study was to examine the functional between acoustic reflex (AR) latency and the intensity and frequency of the eliciting stimulus. AR latency was determined at various intensities for 500 Hz and 300 Hz pure tones, and for wide-band noise. The results of the study indicated that AR latency decreased as stimulus intensity increased for all stimuli; the exact nature of the relationship depended on the stimulus, however. Latency differences between the stimuli at a given sound pressure level tended to disappear at higher presentation levels. Of particular interest was the dependency of inter- and intrasubject variability on parameters of the eliciting stimulus. The data do no indicate that AR latency is mediated solely by the loudness of the eliciting stimulus.", "contents": "Acoustic reflex latency as a function of frequency and intensity of eliciting stimulus. The purpose of the present study was to examine the functional between acoustic reflex (AR) latency and the intensity and frequency of the eliciting stimulus. AR latency was determined at various intensities for 500 Hz and 300 Hz pure tones, and for wide-band noise. The results of the study indicated that AR latency decreased as stimulus intensity increased for all stimuli; the exact nature of the relationship depended on the stimulus, however. Latency differences between the stimuli at a given sound pressure level tended to disappear at higher presentation levels. Of particular interest was the dependency of inter- and intrasubject variability on parameters of the eliciting stimulus. The data do no indicate that AR latency is mediated solely by the loudness of the eliciting stimulus."}
{"id": "PMID:185185", "title": "An epornitic of duck viral enteritis in a zoological park.", "content": "An epornitic of duck viral enteritis occurred at the National Zoological Park in the spring of 1975. The disease affected 8 different species of ducks; geese and swan were spared. Diagnosis was based on characteristic pathologic changes, with herpetic inclusion bodies in the epithelium of the digestive tract and liver, and by viral isolation from 4 ducks. An experimental attenuated live-virus vaccine and sanitizing procedures were used to control the epornitic.", "contents": "An epornitic of duck viral enteritis in a zoological park. An epornitic of duck viral enteritis occurred at the National Zoological Park in the spring of 1975. The disease affected 8 different species of ducks; geese and swan were spared. Diagnosis was based on characteristic pathologic changes, with herpetic inclusion bodies in the epithelium of the digestive tract and liver, and by viral isolation from 4 ducks. An experimental attenuated live-virus vaccine and sanitizing procedures were used to control the epornitic."}
{"id": "PMID:185186", "title": "Necropsy and laboratory findings in free-living deer in South Dakota.", "content": "In a diagnostic survey of diseases in wild white-tailed deer (62 cases) and mule deer (12 cases) the most common findings were traumatic injury (20%), nontraumatic hemorrhage (13%), polioencephalomalacia (11%), and bacterial infections (9%). Although epizootic hemorrhagic disease was suspected in several cases, the virus was isolated from only 1 white-tailed deer.", "contents": "Necropsy and laboratory findings in free-living deer in South Dakota. In a diagnostic survey of diseases in wild white-tailed deer (62 cases) and mule deer (12 cases) the most common findings were traumatic injury (20%), nontraumatic hemorrhage (13%), polioencephalomalacia (11%), and bacterial infections (9%). Although epizootic hemorrhagic disease was suspected in several cases, the virus was isolated from only 1 white-tailed deer."}
{"id": "PMID:185187", "title": "Parameters of fixation of the putative pain afferents in the ureter: preservation of the dense cores of the large vesicles in the axonal terminals.", "content": "A study has been undertaken of the effects of a number of fixation procedures on the appearance of axons in the ureteric plexuses of the rat, and especially on the appearance of the dense-cored vesicles in those axons which have recently been characterized as pain afferents. Terminals were readily identified in material fixed by perfusion with glutaraldehyde, and many of them contained few if any vesicles. After fixation by immersion in cold glutaraldehyde terminals were not easy to identify because of the loss of microtubules. Immersion fixation in glutaraldehyde produced changes in the number and distribution of the vesicles in the axons which accentuated the similarity of the 'vesicle-containing regions' to the terminals of so-called 'purinergic' axons. Few of the dense-cored vesicles seen in glutaraldehyde-fixed material were preserved by fixation in permanganate, osmium or paraformaldehyde. The way dense-cored vesicles were or were not preserved by the various fixatives used indicated major differences between such cores and those of the vesicles in adrenergic axons. There was also evidence from the study of osmium-fixed material that both the number and appearance of the vesicles can be affected by the type of buffer used: the presence of more vesicles after fixation in osmium buffered with veronal than after osmium buffered in other ways was attributed to the membrane-stabilizing properties of veronal.", "contents": "Parameters of fixation of the putative pain afferents in the ureter: preservation of the dense cores of the large vesicles in the axonal terminals. A study has been undertaken of the effects of a number of fixation procedures on the appearance of axons in the ureteric plexuses of the rat, and especially on the appearance of the dense-cored vesicles in those axons which have recently been characterized as pain afferents. Terminals were readily identified in material fixed by perfusion with glutaraldehyde, and many of them contained few if any vesicles. After fixation by immersion in cold glutaraldehyde terminals were not easy to identify because of the loss of microtubules. Immersion fixation in glutaraldehyde produced changes in the number and distribution of the vesicles in the axons which accentuated the similarity of the 'vesicle-containing regions' to the terminals of so-called 'purinergic' axons. Few of the dense-cored vesicles seen in glutaraldehyde-fixed material were preserved by fixation in permanganate, osmium or paraformaldehyde. The way dense-cored vesicles were or were not preserved by the various fixatives used indicated major differences between such cores and those of the vesicles in adrenergic axons. There was also evidence from the study of osmium-fixed material that both the number and appearance of the vesicles can be affected by the type of buffer used: the presence of more vesicles after fixation in osmium buffered with veronal than after osmium buffered in other ways was attributed to the membrane-stabilizing properties of veronal."}
{"id": "PMID:185188", "title": "Naturally-occurring degeneration in chick muscle development: ultrastructure of the M. complexus.", "content": "Ultrastructural study of the M. complexus muscle of the chick embryo has demonstrated two populations of fibres: the more common is the normal myotube or muscle fibre, which was observed in various stages of development; the other shows myofibrillar contractions which, at their greatest degree, produce the appearance of an amorphous mass of myofilaments. The contracted fibre had rounded and swollen mitochondria, and vacuoles (autophagic) containing glycogen, and it exhibited a cleavage of the cell which isolated the nuclear region from the main body of the fibre. When the fibres were less contracted they resembled degenerative mammalian fast-twitch-oxidative-glycolytic fibres after immobilization. The more normal fibre population was identical with that of the pectoralis muscle, which was used as a control. These results suggest that the contracted fibres are degenerating, which agrees with conclusions by earlier investigators using light miscroscopy.", "contents": "Naturally-occurring degeneration in chick muscle development: ultrastructure of the M. complexus. Ultrastructural study of the M. complexus muscle of the chick embryo has demonstrated two populations of fibres: the more common is the normal myotube or muscle fibre, which was observed in various stages of development; the other shows myofibrillar contractions which, at their greatest degree, produce the appearance of an amorphous mass of myofilaments. The contracted fibre had rounded and swollen mitochondria, and vacuoles (autophagic) containing glycogen, and it exhibited a cleavage of the cell which isolated the nuclear region from the main body of the fibre. When the fibres were less contracted they resembled degenerative mammalian fast-twitch-oxidative-glycolytic fibres after immobilization. The more normal fibre population was identical with that of the pectoralis muscle, which was used as a control. These results suggest that the contracted fibres are degenerating, which agrees with conclusions by earlier investigators using light miscroscopy."}
{"id": "PMID:185189", "title": "Inclusions in the human thyroid.", "content": "A survey of the thyroids of 350 infants and children suggests that the presence of thymus and parathyroid tissue within the thyroid is so common as to be classified as normal. One in a hundred thyroids contains masses of cartilage, and one in a hundred shows small foci of ciliated epithelium. Compact masses of dark-staining cells that bear a resemblance to primitive follicular plate cells are also so common as to raise the possibility of their being a normal component with, possibly, an endocrine function. It has been suggested that they produce calcitonin, but this could not be confirmed. Peculiar granular cells replacing follicle cells were also noticed.", "contents": "Inclusions in the human thyroid. A survey of the thyroids of 350 infants and children suggests that the presence of thymus and parathyroid tissue within the thyroid is so common as to be classified as normal. One in a hundred thyroids contains masses of cartilage, and one in a hundred shows small foci of ciliated epithelium. Compact masses of dark-staining cells that bear a resemblance to primitive follicular plate cells are also so common as to raise the possibility of their being a normal component with, possibly, an endocrine function. It has been suggested that they produce calcitonin, but this could not be confirmed. Peculiar granular cells replacing follicle cells were also noticed."}
{"id": "PMID:185192", "title": "The relationship of the house-dust mite to respiratory allergy.", "content": "1. The house-dust mite is a potent and important allergen. 2. 11.2% of patients with perennial respiratory allergy are allergic to the mite allergen and not to the various dust allergens. 3. 39.6% of the patients allergic to the allergens of house-dust are allergic to the allergen of the house-dust mites. 4. 23.7% of patients allergic to the allergens of house-dust are not allergic to the allergen of the house-dust mite. 5. 25.2% of patients with perennial respiratory allergy are not allergic to either the house-dust or mite allergens. 6. Endo, Center, or both dusts were negative in 222 cases, or 36.4%. 7.house-dust mites were negative in 297 cases, or 48.9%. 8. Positive intracutaneous skin tests with house-dust mite extract correlated with only 60.5% of the patients. Negative skin tests correlated with 67.3% of the patients.", "contents": "The relationship of the house-dust mite to respiratory allergy. 1. The house-dust mite is a potent and important allergen. 2. 11.2% of patients with perennial respiratory allergy are allergic to the mite allergen and not to the various dust allergens. 3. 39.6% of the patients allergic to the allergens of house-dust are allergic to the allergen of the house-dust mites. 4. 23.7% of patients allergic to the allergens of house-dust are not allergic to the allergen of the house-dust mite. 5. 25.2% of patients with perennial respiratory allergy are not allergic to either the house-dust or mite allergens. 6. Endo, Center, or both dusts were negative in 222 cases, or 36.4%. 7.house-dust mites were negative in 297 cases, or 48.9%. 8. Positive intracutaneous skin tests with house-dust mite extract correlated with only 60.5% of the patients. Negative skin tests correlated with 67.3% of the patients."}
{"id": "PMID:185193", "title": "Arginine-sensitive phenotype of mutations in pyrA of Salmonella typhimurium: role of ornithine carbamyltransferase in the assembly of mutant carbamylphosphate synthetase.", "content": "The phenotype of certain mutations in pyrA, the gene encoding carbamylphosphate synthetase (CPSase), is expressed only in the presence od exogenous arginine. In unsupplemented media, synthesis of carbamylphosphate and growth was almost normal; in arginine-containing media, synthesis of carbamylphosphate stopped, as did growth, as a consequence of starvation for pyrimidine. Genetic and biochemical evidence suggests that arginine exerts this inhibition by repressing the synthesis of ornithine carbamyltransferase (OTCase), the intracellular presence of which is required for assembly of the unequal subunits and proper functioning of the mutant CPSase. After the addition of arginine to a culture of the mutant, CPSase activity (glutamine dependent) characteristic of the intact holoenzyme progressively decreased, whereas activity (ammonia dependent) characteristic of the free large (alpha) subunit increased. Extracts of mutant cells contain free small (beta) subunits, as demonstrated directly by in vitro complementation using purified alpha subunits from wild type. The mutant enzyme from cultures grown in the presence of arginine had a markedly decreased affinity for adenosine 5'-triphosphate. Mutations in argR that cause depressed synthesis of OTCase suppressed the phenotype, and a certain mutation in argI, the gene encoding OTCase, enhanced it. In vitro experiments using purified enzyme confirm the stimulatory effect of OTCase on the activity of mutant CPSase.", "contents": "Arginine-sensitive phenotype of mutations in pyrA of Salmonella typhimurium: role of ornithine carbamyltransferase in the assembly of mutant carbamylphosphate synthetase. The phenotype of certain mutations in pyrA, the gene encoding carbamylphosphate synthetase (CPSase), is expressed only in the presence od exogenous arginine. In unsupplemented media, synthesis of carbamylphosphate and growth was almost normal; in arginine-containing media, synthesis of carbamylphosphate stopped, as did growth, as a consequence of starvation for pyrimidine. Genetic and biochemical evidence suggests that arginine exerts this inhibition by repressing the synthesis of ornithine carbamyltransferase (OTCase), the intracellular presence of which is required for assembly of the unequal subunits and proper functioning of the mutant CPSase. After the addition of arginine to a culture of the mutant, CPSase activity (glutamine dependent) characteristic of the intact holoenzyme progressively decreased, whereas activity (ammonia dependent) characteristic of the free large (alpha) subunit increased. Extracts of mutant cells contain free small (beta) subunits, as demonstrated directly by in vitro complementation using purified alpha subunits from wild type. The mutant enzyme from cultures grown in the presence of arginine had a markedly decreased affinity for adenosine 5'-triphosphate. Mutations in argR that cause depressed synthesis of OTCase suppressed the phenotype, and a certain mutation in argI, the gene encoding OTCase, enhanced it. In vitro experiments using purified enzyme confirm the stimulatory effect of OTCase on the activity of mutant CPSase."}
{"id": "PMID:185194", "title": "Iron-chelating compound from Mycobacterium avium.", "content": "A iron-chelating monohydroxamate was isolated from cultures of Mycobacterium avium grown on an iron-limiting medium. The hydroxyamate metabolite was characterized by chemical degradation and spectral measurements as L-alpha-asparaginyl-L-alpha-(N-hydroxy)-asparagine.", "contents": "Iron-chelating compound from Mycobacterium avium. A iron-chelating monohydroxamate was isolated from cultures of Mycobacterium avium grown on an iron-limiting medium. The hydroxyamate metabolite was characterized by chemical degradation and spectral measurements as L-alpha-asparaginyl-L-alpha-(N-hydroxy)-asparagine."}
{"id": "PMID:185195", "title": "Stimulatory effect of lithium ion on proline transport by whole cells of Escherichia coli.", "content": "The effect of monovalent cations on proline transport in whole cells of Escherichia coli K-12 has been examined. Lithium ion added to the uptake medium stimulated proline transport severalfold and K+ and Na+ were slightly effective, whereas Rb+, Cs+, and NH4+ were completely without effect. The stimulatory effect of Li+ on proline transport was not due to an increase in osmolarity of the uptake medium, and d 5 mM p-chloromercuribenzene sulfonic acid completely blocked this effect of Li+ without having any effect on the basal rate of proline transport. The Arrhenius plots for Li+-stimulated transport showed a clear transition point at 35 degrees C in addition to 20 degrees C which was also detectable in the basal transport. Lithium ion stimulated proline transport synergistically in the presence of glucose and succinate as a carbon source. The addition of 2.5 mM KCN or 0.5 mM arsenate did not inhibit this synergistic effect, although the presence of these inhibitors inhibited completely the stimulation of proline transport induced by the addition of carbon source. Carbonylcyanide m-chlorophenylhydrazone and 2,4-dinitrophenol blocked both the basal and Li+-stimulated proline transport. When membrane potential of E. coli cells was measured by the dibenzyldimethylammonium uptake method, the incubation of Li+ with the cells did not affect the preexisting membrane potential. These results suggest that Li+ stimulates proline transport by intact cells of E. coli in a manner somewhat affecting membrane component(s) different from the transport carrier of proline. It is uncertain whether the effect of Li+ is directly involved in the mechanisms of energy coupling of proline transport.", "contents": "Stimulatory effect of lithium ion on proline transport by whole cells of Escherichia coli. The effect of monovalent cations on proline transport in whole cells of Escherichia coli K-12 has been examined. Lithium ion added to the uptake medium stimulated proline transport severalfold and K+ and Na+ were slightly effective, whereas Rb+, Cs+, and NH4+ were completely without effect. The stimulatory effect of Li+ on proline transport was not due to an increase in osmolarity of the uptake medium, and d 5 mM p-chloromercuribenzene sulfonic acid completely blocked this effect of Li+ without having any effect on the basal rate of proline transport. The Arrhenius plots for Li+-stimulated transport showed a clear transition point at 35 degrees C in addition to 20 degrees C which was also detectable in the basal transport. Lithium ion stimulated proline transport synergistically in the presence of glucose and succinate as a carbon source. The addition of 2.5 mM KCN or 0.5 mM arsenate did not inhibit this synergistic effect, although the presence of these inhibitors inhibited completely the stimulation of proline transport induced by the addition of carbon source. Carbonylcyanide m-chlorophenylhydrazone and 2,4-dinitrophenol blocked both the basal and Li+-stimulated proline transport. When membrane potential of E. coli cells was measured by the dibenzyldimethylammonium uptake method, the incubation of Li+ with the cells did not affect the preexisting membrane potential. These results suggest that Li+ stimulates proline transport by intact cells of E. coli in a manner somewhat affecting membrane component(s) different from the transport carrier of proline. It is uncertain whether the effect of Li+ is directly involved in the mechanisms of energy coupling of proline transport."}
{"id": "PMID:185196", "title": "Restriction enzymes do not play a significant role in Haemophilus homospecific or heterospecific transformation.", "content": "Competent Haemophilus influenzae Rd recipients, either as phage HP1 restricting (r+) or nonrestricting (r-) nonlysogens or defective lysogens, were exposed to deoxyribonucleic acids from various wild-type phage HP1 lysogenic H. influenzae serotype strains (non-encapsulated derivatives of serotypes a,b, c, d, and e), to DNA from lysogenic Haemophilus parahaemolyticus, and to DNA from modified and nonmodified phage HP1. Transformation of antibiotic resistance markers and of prophage markers in homospecific crosses was observed to be unaffected by the recipient restriction phenotype, whereas the transfection response was much reduced in r+ recipients. Heterospecific transformation of prophage markers was reduced by only 80 to 90%, whereas antibiotic resistance marker transformation was 1,000 to 10,000 times lower. Heterspecific transfection was at least 100 times lower than homospecific transfection in both r+ and r- recipients. The general conclusion is that neither class I nor class II restriction enzymes affect significantly the transformation efficiency in homospecific and heterospecific crosses. The efficiency of heterospecific transformation may depend mainly on the deoxyribonucleic acid homology in the genetic marker region.", "contents": "Restriction enzymes do not play a significant role in Haemophilus homospecific or heterospecific transformation. Competent Haemophilus influenzae Rd recipients, either as phage HP1 restricting (r+) or nonrestricting (r-) nonlysogens or defective lysogens, were exposed to deoxyribonucleic acids from various wild-type phage HP1 lysogenic H. influenzae serotype strains (non-encapsulated derivatives of serotypes a,b, c, d, and e), to DNA from lysogenic Haemophilus parahaemolyticus, and to DNA from modified and nonmodified phage HP1. Transformation of antibiotic resistance markers and of prophage markers in homospecific crosses was observed to be unaffected by the recipient restriction phenotype, whereas the transfection response was much reduced in r+ recipients. Heterospecific transformation of prophage markers was reduced by only 80 to 90%, whereas antibiotic resistance marker transformation was 1,000 to 10,000 times lower. Heterspecific transfection was at least 100 times lower than homospecific transfection in both r+ and r- recipients. The general conclusion is that neither class I nor class II restriction enzymes affect significantly the transformation efficiency in homospecific and heterospecific crosses. The efficiency of heterospecific transformation may depend mainly on the deoxyribonucleic acid homology in the genetic marker region."}
{"id": "PMID:185197", "title": "Isolation and partial characterization of an argR mutant of Salmonella typhimurium.", "content": "An arginine regulatory mutant (i.e., mutated in the argR gene) has been isolated from a strain of Salmonella typhimurium LT2. The argR mutant was found to excrete arginine into the growth medium with glycerol but not glucose as carbon source. Constitutive synthesis of arginine biosynthetic enzymes was observed. Whereas previous results (A. T. Abd-E1-A1 and J. L. Ingraham, Abstr. Annu. Meet. Am. Soc. Microbiol. 1975, K169, p. 175) have shown constitutive synthesis of carbamyl phosphate synthetase in the argR mutant, the regulation of the synthesis of the last five enzymes of the pyrimidine pathway was unaffected. However, in pyrH mutants, known to exhibit derepressed synthesis of the pyrimidine enzymes, a 10-fold derepression of ornithine transcarbamylase was observed.", "contents": "Isolation and partial characterization of an argR mutant of Salmonella typhimurium. An arginine regulatory mutant (i.e., mutated in the argR gene) has been isolated from a strain of Salmonella typhimurium LT2. The argR mutant was found to excrete arginine into the growth medium with glycerol but not glucose as carbon source. Constitutive synthesis of arginine biosynthetic enzymes was observed. Whereas previous results (A. T. Abd-E1-A1 and J. L. Ingraham, Abstr. Annu. Meet. Am. Soc. Microbiol. 1975, K169, p. 175) have shown constitutive synthesis of carbamyl phosphate synthetase in the argR mutant, the regulation of the synthesis of the last five enzymes of the pyrimidine pathway was unaffected. However, in pyrH mutants, known to exhibit derepressed synthesis of the pyrimidine enzymes, a 10-fold derepression of ornithine transcarbamylase was observed."}
{"id": "PMID:185198", "title": "Kinetics of light-dark CO2 fixation and glucose assimilation by Aphanocapsa 6714.", "content": "Cells of Aphanocapsa 6714 were subjected to alternating ligh-dark periods (flashing-light experiments). The corresponding activation (in the light) and inactivation (in the dark) of the reductive pentose cycle was measured, in vivo, from initial rates of 14CO2 incorporation and also by changes in the total concentration of 14C and 32P in soluble metabolites. Two principle sites of metabolic regulation were detected: (i) CO2 fixation was inactivated 15 to 20 s after removal of the light source, but reactivated rapidly on reentering the light; (ii) hydrolysis of fructose-1,6-diphosphate (FDP) and sedoheptulose-1,7-diphosphate (SDP) by their respective phosphatase(s) (FDP + SDPase) was rapidly inhibited in the dark but only slowly reactivated in the light. The time required for reactivation of FDP + SDPase, in the light, was on the order of 20 to 30 s. As a consequence of the timing of these inactivation-reactivation reactions, newly fixed CO2 accumulated in the FDP and SDP pools during the flashing-light experiments. Changes in the concentrations of the adenylate pools (mainly in the levels of adenosine 5'-triphosphate and adenosine diphosphate) were fast in comparison to the inactivation-reactivation reactions in the reductive pentose cycle. Thus, these regulatory effects may not be under the control of the adenylates in this organism. The activation of CO2 fixation in the light is at least in part due to activation of phosphoribulokinase, which is required for formation of ribulose-1,5-diphoshate, the carboxylation substrate. Phosphoribulokinase activity in crude extracts was found to be dependent on the presence of strong reducing agents such as dithiothreitol, but not significantly dependent on adenylate levels, although adenosine 5'-triphosphate is a substrate.", "contents": "Kinetics of light-dark CO2 fixation and glucose assimilation by Aphanocapsa 6714. Cells of Aphanocapsa 6714 were subjected to alternating ligh-dark periods (flashing-light experiments). The corresponding activation (in the light) and inactivation (in the dark) of the reductive pentose cycle was measured, in vivo, from initial rates of 14CO2 incorporation and also by changes in the total concentration of 14C and 32P in soluble metabolites. Two principle sites of metabolic regulation were detected: (i) CO2 fixation was inactivated 15 to 20 s after removal of the light source, but reactivated rapidly on reentering the light; (ii) hydrolysis of fructose-1,6-diphosphate (FDP) and sedoheptulose-1,7-diphosphate (SDP) by their respective phosphatase(s) (FDP + SDPase) was rapidly inhibited in the dark but only slowly reactivated in the light. The time required for reactivation of FDP + SDPase, in the light, was on the order of 20 to 30 s. As a consequence of the timing of these inactivation-reactivation reactions, newly fixed CO2 accumulated in the FDP and SDP pools during the flashing-light experiments. Changes in the concentrations of the adenylate pools (mainly in the levels of adenosine 5'-triphosphate and adenosine diphosphate) were fast in comparison to the inactivation-reactivation reactions in the reductive pentose cycle. Thus, these regulatory effects may not be under the control of the adenylates in this organism. The activation of CO2 fixation in the light is at least in part due to activation of phosphoribulokinase, which is required for formation of ribulose-1,5-diphoshate, the carboxylation substrate. Phosphoribulokinase activity in crude extracts was found to be dependent on the presence of strong reducing agents such as dithiothreitol, but not significantly dependent on adenylate levels, although adenosine 5'-triphosphate is a substrate."}
{"id": "PMID:185199", "title": "Effect of polymyxin on the outer membrane of Salmonella typhimurium: freeze-fracture studies.", "content": "Polymyxin-caused projections on the cell surface of Salmonella typhimurium were seen as depressions in the outer concave fracture face and as protrusions in the outer convex fracture face, indicating participation of both leaflets of the outer membrane in these projections.", "contents": "Effect of polymyxin on the outer membrane of Salmonella typhimurium: freeze-fracture studies. Polymyxin-caused projections on the cell surface of Salmonella typhimurium were seen as depressions in the outer concave fracture face and as protrusions in the outer convex fracture face, indicating participation of both leaflets of the outer membrane in these projections."}
{"id": "PMID:185200", "title": "Aminoacyl transfer RNA formation. VII. Lack of correlation between aminoacylation and PPi-ATP exchange catalyzed by isoleucyl-tRNA synthetase of Escherichia coli in the presence of various divalent cations.", "content": "Isoleucyl-tRNA formation and isoleucine-dependent PPi-ATP exchange catalyzed by purified isoleucyl-tRNA synthetase [EC 6.1.1.5] of Escherichia coli were studied in the presence of various amounts of either Mg2+, Ca2+, Fe2+, Ni2+, or Cu2+. In the presence of Mg2+, isoleucine-dependent PPi-ATP exchange was observed in parallel with isoleucyl-tRNA formation, while in the presence of Ca2+, isoleucyl-tRNA formation was observed without isoleucine-dependent PPi-ATP exchange. Moreover, isoleucine-dependent PPi-ATP exchange was much more in the presence of Fe2+ than in the presence of Mg2+, while little isoleucyl-tRNA was formed in the presence of Fe2+. In the presence of Ni2+ or Cu2+, neither reaction was observed. These data, indicating that formation of an isoleucyl-AMP-enzyme complex is not a necessary step in isoleucyl-tRNA formation, support the existence of a concerted mechanism of isoleucyl-tRNA formation in E. coli.", "contents": "Aminoacyl transfer RNA formation. VII. Lack of correlation between aminoacylation and PPi-ATP exchange catalyzed by isoleucyl-tRNA synthetase of Escherichia coli in the presence of various divalent cations. Isoleucyl-tRNA formation and isoleucine-dependent PPi-ATP exchange catalyzed by purified isoleucyl-tRNA synthetase [EC 6.1.1.5] of Escherichia coli were studied in the presence of various amounts of either Mg2+, Ca2+, Fe2+, Ni2+, or Cu2+. In the presence of Mg2+, isoleucine-dependent PPi-ATP exchange was observed in parallel with isoleucyl-tRNA formation, while in the presence of Ca2+, isoleucyl-tRNA formation was observed without isoleucine-dependent PPi-ATP exchange. Moreover, isoleucine-dependent PPi-ATP exchange was much more in the presence of Fe2+ than in the presence of Mg2+, while little isoleucyl-tRNA was formed in the presence of Fe2+. In the presence of Ni2+ or Cu2+, neither reaction was observed. These data, indicating that formation of an isoleucyl-AMP-enzyme complex is not a necessary step in isoleucyl-tRNA formation, support the existence of a concerted mechanism of isoleucyl-tRNA formation in E. coli."}
{"id": "PMID:185201", "title": "Induction of ornithine decarboxylase in cultured mouse L cells. I. Effects of cellular growth, hormones, and actinomycin D.", "content": "The activity of ornithine decarboxylase [EC 4.1.1.17] (ODC) in mouse L cells in the confluent state was induced within 4 hr by cyclic AMP (cAMP) or by insulin. During growth of L cells the concentration of cAMP increased first, then induction of ODC occurred and finally the cell number increased: the levels of cAMP and ODC increased only transitorily and returned to the basal levels when the cells become confluent. In growing cultures, however, the presence of cAMP reduced induction of ODC and cell growth. These results suggest that cAMP is involved in induction of ODC and that its concentration may be important for enzyme induction as well as for cell growth. Actinomycin D with or without these inducers stimulated induction of ODC in L cells, whereas cycloheximide inhibited it, suggesting that these hormones affect the translational level of ODC synthesis. The effect of actinomycin D on induction of ODC was much greater in non-growing cells than in growing cells. It was also found that the half life of ODC was 81 min in non-growing cells and 112 min in growing cells. This suggests that turnover of the enzyme is more rapid in the non-growing than in the growing state and that there may be an RNA fraction which controls its turnover and which also has a very short half life.", "contents": "Induction of ornithine decarboxylase in cultured mouse L cells. I. Effects of cellular growth, hormones, and actinomycin D. The activity of ornithine decarboxylase [EC 4.1.1.17] (ODC) in mouse L cells in the confluent state was induced within 4 hr by cyclic AMP (cAMP) or by insulin. During growth of L cells the concentration of cAMP increased first, then induction of ODC occurred and finally the cell number increased: the levels of cAMP and ODC increased only transitorily and returned to the basal levels when the cells become confluent. In growing cultures, however, the presence of cAMP reduced induction of ODC and cell growth. These results suggest that cAMP is involved in induction of ODC and that its concentration may be important for enzyme induction as well as for cell growth. Actinomycin D with or without these inducers stimulated induction of ODC in L cells, whereas cycloheximide inhibited it, suggesting that these hormones affect the translational level of ODC synthesis. The effect of actinomycin D on induction of ODC was much greater in non-growing cells than in growing cells. It was also found that the half life of ODC was 81 min in non-growing cells and 112 min in growing cells. This suggests that turnover of the enzyme is more rapid in the non-growing than in the growing state and that there may be an RNA fraction which controls its turnover and which also has a very short half life."}
{"id": "PMID:185202", "title": "3-Dehydroquinate synthase in germinating Phaseolus mungo seedlings.", "content": "Dehydroquinate synthase, an enzyme catalyzing the conversion of 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) to 3-dehydroquinate, was detected in cell-free extracts of etiolated Phaseolus mungo seedlings. The reaction product, 3-dehydroquinate, formed from [1-14C]DAHP was identified by paper-radiochromatography. The enzyme required NAD+ and Co2+ for activity.", "contents": "3-Dehydroquinate synthase in germinating Phaseolus mungo seedlings. Dehydroquinate synthase, an enzyme catalyzing the conversion of 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) to 3-dehydroquinate, was detected in cell-free extracts of etiolated Phaseolus mungo seedlings. The reaction product, 3-dehydroquinate, formed from [1-14C]DAHP was identified by paper-radiochromatography. The enzyme required NAD+ and Co2+ for activity."}
{"id": "PMID:185203", "title": "Alterations in enzyme and cytochrome profiles of Rana catesbeiana liver organelles during thyroxine-induced metamorphosis. Changes in membrane-localized phosphohydrolases, oxidoreductases, and cytochrome levels in response to in vivo thyroxine administration.", "content": "A primary objective of the present study has been to determine the changes which occur in Rana catesbeiana liver organelle membranes during thyroxine-induced metamorphosis. To this end, enzyme and cytochrome profiles were determined for mitochondria, microsomes, and nuclear membrane fractions isolated from livers of R. catesbeiana tadpoles which had been fasted for 6 days at 15 +/- 0.5 degrees and then immersed in thyroxine, 2.6 X 10(-8) M, for periods of up to 12 days at 23.5 +/- 0.4 degrees. The ratio of total succinate-cytochrome c reductase activity in the initial homogenate fraction to the total activity of this mitochondrial \"marker\" enzyme recovered in the final mitochondrial fraction remained constant, approximately 0.5, throughout the course of thyroxine treatment; however, after a 3- to 4-day latency the mitochondrial protein mass recovered per unit mass of initial homogenate protein was found to increase significantly (approximately 2-fold by Day 10 of thyroxine treatment). A similar increase was also observed in the yield of microsomal, but not nuclear membrane, protein mass as a function of thyroxine treatment. Prolonged thyroxine treatment (12 days) resulted in approximately 50% decreases in tadpole liver homogenate and microsomal NADH-cytochrome c reductase specific activities; in contrast, mitochondrial and nuclear membrane NADH-cytochrome c reductase specific activities were not altered under the same conditions. In addition, homogenate and microsomal NADPH-cytochrome c reductase specific activities were found to have increased significantly after 12 days of thyroxine treatment; however, the specific activity of NADPH-cytochrome c reductase in the mitochondrial fraction was unchanged. It was also observed that thyroxine treatment resulted in increases in homogenate and microsomal glucose-6-phosphatase specific activities, whereas the mitochondrial as well as nuclear membrane glucose-6-phosphatase specific activities remained unchanged. Furthermore, in contrast to homogenate and mitochondrial monoamine oxidase specific activities, which decreased 30 and 40%, respectively, as a consequence of thyroxine treatment (12 days), the succinate-cytochrome c reductase and oligomycin-sensitive Mg2+ ATPase specific activities determined for these fractions increased significantly. In all instances, changes as a result of thyroxine treatment in membrane-localized homogenate or organelle enzyme specific activities were apparent only after a 3- to 4-day initial latent period. The in vitro effects of thyroxine (10(-10) - 10(-5) M) on the membrane-localized enzyme activities examined in this study were either negligible or, as in the case of mitochondrial succinate-cytochrome c reductase and microsomal NADH-cytochrome c reductase, opposite to the changes observed in response to in vivo thyroxine treatment, with the exception of microsomal NADPH-cytochrome c reductase activity which was enhanced approximately 2-fold by 10(-5) M thyroxine...", "contents": "Alterations in enzyme and cytochrome profiles of Rana catesbeiana liver organelles during thyroxine-induced metamorphosis. Changes in membrane-localized phosphohydrolases, oxidoreductases, and cytochrome levels in response to in vivo thyroxine administration. A primary objective of the present study has been to determine the changes which occur in Rana catesbeiana liver organelle membranes during thyroxine-induced metamorphosis. To this end, enzyme and cytochrome profiles were determined for mitochondria, microsomes, and nuclear membrane fractions isolated from livers of R. catesbeiana tadpoles which had been fasted for 6 days at 15 +/- 0.5 degrees and then immersed in thyroxine, 2.6 X 10(-8) M, for periods of up to 12 days at 23.5 +/- 0.4 degrees. The ratio of total succinate-cytochrome c reductase activity in the initial homogenate fraction to the total activity of this mitochondrial \"marker\" enzyme recovered in the final mitochondrial fraction remained constant, approximately 0.5, throughout the course of thyroxine treatment; however, after a 3- to 4-day latency the mitochondrial protein mass recovered per unit mass of initial homogenate protein was found to increase significantly (approximately 2-fold by Day 10 of thyroxine treatment). A similar increase was also observed in the yield of microsomal, but not nuclear membrane, protein mass as a function of thyroxine treatment. Prolonged thyroxine treatment (12 days) resulted in approximately 50% decreases in tadpole liver homogenate and microsomal NADH-cytochrome c reductase specific activities; in contrast, mitochondrial and nuclear membrane NADH-cytochrome c reductase specific activities were not altered under the same conditions. In addition, homogenate and microsomal NADPH-cytochrome c reductase specific activities were found to have increased significantly after 12 days of thyroxine treatment; however, the specific activity of NADPH-cytochrome c reductase in the mitochondrial fraction was unchanged. It was also observed that thyroxine treatment resulted in increases in homogenate and microsomal glucose-6-phosphatase specific activities, whereas the mitochondrial as well as nuclear membrane glucose-6-phosphatase specific activities remained unchanged. Furthermore, in contrast to homogenate and mitochondrial monoamine oxidase specific activities, which decreased 30 and 40%, respectively, as a consequence of thyroxine treatment (12 days), the succinate-cytochrome c reductase and oligomycin-sensitive Mg2+ ATPase specific activities determined for these fractions increased significantly. In all instances, changes as a result of thyroxine treatment in membrane-localized homogenate or organelle enzyme specific activities were apparent only after a 3- to 4-day initial latent period. The in vitro effects of thyroxine (10(-10) - 10(-5) M) on the membrane-localized enzyme activities examined in this study were either negligible or, as in the case of mitochondrial succinate-cytochrome c reductase and microsomal NADH-cytochrome c reductase, opposite to the changes observed in response to in vivo thyroxine treatment, with the exception of microsomal NADPH-cytochrome c reductase activity which was enhanced approximately 2-fold by 10(-5) M thyroxine..."}
{"id": "PMID:185204", "title": "Interactions of the actin and nucleotide binding sites on myosin subfragment 1.", "content": "The effects of selected nucleotides (N) on the binding of myosin subfragment 1 (S-1) and pure F-actin (A) were measured by time-resolved fluorescence depolarization for 0.15 M KCl, pH 7.0 at 4 degrees. The association constants K'A, KN, and K'N in the scheme (see article), were determined for the magnesium salts of ADP, adenyl-5'-yl imidodiphosphate AMP-P(NH)P, and PPi. The nucleotide binding site on S-1 was \"mapped\" with respect to its interaction on the actin binding site. The subsites were the beta- and gamma-phosphoryl groups of ATP bind had the largest effects. A quantitative measure of the interaction, the interaction free energy, was defined as -RT ln (KA/K'A). For ADP, K'A was 2.7 X 10(5) M-1 and the interaction free energy was -4.67 kJ M-1. For AMP-P(NH)P and PPi it was much larger. A ternary complex was shown to exist for ADP, S-1, and actin in the presence of Mg2+ and evidence from AMP-P(NH)P and PPi measurements indicated that ATP also likely forms a ternary complex. The mechanism of (S-1)-actin dissociation is discussed in light of these results.", "contents": "Interactions of the actin and nucleotide binding sites on myosin subfragment 1. The effects of selected nucleotides (N) on the binding of myosin subfragment 1 (S-1) and pure F-actin (A) were measured by time-resolved fluorescence depolarization for 0.15 M KCl, pH 7.0 at 4 degrees. The association constants K'A, KN, and K'N in the scheme (see article), were determined for the magnesium salts of ADP, adenyl-5'-yl imidodiphosphate AMP-P(NH)P, and PPi. The nucleotide binding site on S-1 was \"mapped\" with respect to its interaction on the actin binding site. The subsites were the beta- and gamma-phosphoryl groups of ATP bind had the largest effects. A quantitative measure of the interaction, the interaction free energy, was defined as -RT ln (KA/K'A). For ADP, K'A was 2.7 X 10(5) M-1 and the interaction free energy was -4.67 kJ M-1. For AMP-P(NH)P and PPi it was much larger. A ternary complex was shown to exist for ADP, S-1, and actin in the presence of Mg2+ and evidence from AMP-P(NH)P and PPi measurements indicated that ATP also likely forms a ternary complex. The mechanism of (S-1)-actin dissociation is discussed in light of these results."}
{"id": "PMID:185205", "title": "Inhibition of gluconeogenesis and lactate formation from pyruvate by N6, O2'-dibutyryl adenosine 3':5'-monophosphate.", "content": "N6,O2-Dibutyryl adenosine 3':5'-monophosphate (Bt2cAMP) inhibits gluconeogenesis and lactate formation but increases ketogenesis by isolated liver cells incubated with high concentrations of pyruvate. The inhibitory effects can not be explained on the basis of an inhibition of the pyruvate dehydrogenase complex nor by a change in the NAD+ oxidation-reduction potential of the mitochondrial compartment. Both oleate and 3-hydroxybutyrate substantially increase the rates of gluconeogenesis and lactate formation from pyruvate but do not overcome the inhibition caused by Bt2cAMP. A decreased effectiveness of pyruvate kinase is proposed to account for the inhibition of both gluconeogenesis and lactate formation by Bt2cAMP. This enzyme catalyzes a step required in the transfer of reducing equivalents from the mitochondrial compartment to the cytoplasm and participates in the formation of glucose and lactate from pyruvate by the overall reaction: 2 pyruvate- + 2 NADHmito + 4 ATP4- + 4 H2O leads to 1/2 glucose + lactate- + 2 NAD+ mito + 4 ADP3- + 4 HPO4(2)- + H+. Inhibition of pyruvate kinase promotes gluconeogenesis with most substrates but inhibits gluconeogenesis from pyruvate for want of cytoplasmic reducing equivalents.", "contents": "Inhibition of gluconeogenesis and lactate formation from pyruvate by N6, O2'-dibutyryl adenosine 3':5'-monophosphate. N6,O2-Dibutyryl adenosine 3':5'-monophosphate (Bt2cAMP) inhibits gluconeogenesis and lactate formation but increases ketogenesis by isolated liver cells incubated with high concentrations of pyruvate. The inhibitory effects can not be explained on the basis of an inhibition of the pyruvate dehydrogenase complex nor by a change in the NAD+ oxidation-reduction potential of the mitochondrial compartment. Both oleate and 3-hydroxybutyrate substantially increase the rates of gluconeogenesis and lactate formation from pyruvate but do not overcome the inhibition caused by Bt2cAMP. A decreased effectiveness of pyruvate kinase is proposed to account for the inhibition of both gluconeogenesis and lactate formation by Bt2cAMP. This enzyme catalyzes a step required in the transfer of reducing equivalents from the mitochondrial compartment to the cytoplasm and participates in the formation of glucose and lactate from pyruvate by the overall reaction: 2 pyruvate- + 2 NADHmito + 4 ATP4- + 4 H2O leads to 1/2 glucose + lactate- + 2 NAD+ mito + 4 ADP3- + 4 HPO4(2)- + H+. Inhibition of pyruvate kinase promotes gluconeogenesis with most substrates but inhibits gluconeogenesis from pyruvate for want of cytoplasmic reducing equivalents."}
{"id": "PMID:185206", "title": "Activation and inhibition of fat cell adenylate cyclase by fluoride.", "content": "Incubation (30 degrees) of fat cell particulate fractions with fluoride before assay in the effective absence of fluoride results in activation of adenylate cyclase. Whereas the effect of fluoride (1.3 to 7 mM) when added to the assay was maximal in less than 2 min, 10 or 15 min of incubation before assay was usually required to produce maximal activation with any given concentration of fluoride. Under both conditions 3 to 5 mM fluoride produced maximal activation. After incubation with fluoride for 5 to 20 min cyclase activity was constant for at least 15 min of assay without fluoride; maximal activity was greater than that produced by fluoride added to the assay system and the concentration required to produce significant activation was lower. Fluoride activation in the assay or during prior incubation could be prevented by pyrophosphate. When added during the early minutes of assays with fluoride, 1.5 mM pyrophosphate, which had little effect on the activity of enzyme previously incubated with fluoride, rapidly reduced activity to essentially basal levels; when added after 10 min its effect was equally rapid but much smaller. It appears that activation is initially reversible by removal of fluoride as it is by addition of pyrophosphate, but becomes largely irreversible by these means with continued exposure to fluoride. Fluoride in the assay system inhibited cyclase activated by isoproterenol or choleragen or by incubation with fluoride prior to assay; inhibition, dependent on fluoride concentration, was maximal at 5.3 mM. Since maximal activity produced by incubation with fluoride before assay exceeded that of nonincubated preparations assayed with fluoride, and was reduced to the latter level when assayed in the presence of fluoride, we infer that inhibition is reversible at a time when fluoride activation is relatively irreversible. Pyrophosphate (1.5 mM), which prevented fluoride activation, did not reduce fluoride inhibition of isoproterenol-, fluoride-, or choleragen-activated cyclase. When 3 mM MnCl2 was present in the assay, inhibition by fluoride was not observed. In descriptive terms, MnCl2 appeared to cause rapid reversal of fluoride inhibition. Thus, fluoride inhibits, in an apparently similar manner, fat cell adenylate cyclase whether it is activated by isoproterenol, fluoride, or choleragen. Although fluoride activation and inhibition can apparently be dissociated or modified differentially, until the mechanism(s) of action of fluoride is elucidated it cannot be concluded that these are totally independent processes.", "contents": "Activation and inhibition of fat cell adenylate cyclase by fluoride. Incubation (30 degrees) of fat cell particulate fractions with fluoride before assay in the effective absence of fluoride results in activation of adenylate cyclase. Whereas the effect of fluoride (1.3 to 7 mM) when added to the assay was maximal in less than 2 min, 10 or 15 min of incubation before assay was usually required to produce maximal activation with any given concentration of fluoride. Under both conditions 3 to 5 mM fluoride produced maximal activation. After incubation with fluoride for 5 to 20 min cyclase activity was constant for at least 15 min of assay without fluoride; maximal activity was greater than that produced by fluoride added to the assay system and the concentration required to produce significant activation was lower. Fluoride activation in the assay or during prior incubation could be prevented by pyrophosphate. When added during the early minutes of assays with fluoride, 1.5 mM pyrophosphate, which had little effect on the activity of enzyme previously incubated with fluoride, rapidly reduced activity to essentially basal levels; when added after 10 min its effect was equally rapid but much smaller. It appears that activation is initially reversible by removal of fluoride as it is by addition of pyrophosphate, but becomes largely irreversible by these means with continued exposure to fluoride. Fluoride in the assay system inhibited cyclase activated by isoproterenol or choleragen or by incubation with fluoride prior to assay; inhibition, dependent on fluoride concentration, was maximal at 5.3 mM. Since maximal activity produced by incubation with fluoride before assay exceeded that of nonincubated preparations assayed with fluoride, and was reduced to the latter level when assayed in the presence of fluoride, we infer that inhibition is reversible at a time when fluoride activation is relatively irreversible. Pyrophosphate (1.5 mM), which prevented fluoride activation, did not reduce fluoride inhibition of isoproterenol-, fluoride-, or choleragen-activated cyclase. When 3 mM MnCl2 was present in the assay, inhibition by fluoride was not observed. In descriptive terms, MnCl2 appeared to cause rapid reversal of fluoride inhibition. Thus, fluoride inhibits, in an apparently similar manner, fat cell adenylate cyclase whether it is activated by isoproterenol, fluoride, or choleragen. Although fluoride activation and inhibition can apparently be dissociated or modified differentially, until the mechanism(s) of action of fluoride is elucidated it cannot be concluded that these are totally independent processes."}
{"id": "PMID:185207", "title": "Studies on the sites in histones phosphorylated by adenosine 3':5'-monophosphate-dependent and guanosine 3':5'-monophosphate-dependent protein kinases.", "content": "Adenosine 3':5'-monophosphate-dependent protein kinase (protein kinase A) purified from silkworm pupae phosphorylated five major fractions of calf thymus histone, whereas guanosine 3':5'-monophosphate-dependent protein kinase (protein kinase G) purified from the same organism reacted preferentially with H1, H2A, and H2B histones. Amino acid analysis of the phosphopeptides which were obtained by proteolytic digestion revealed that both protein kinases A and G showed the abilities to phosphorylate the same serine hydroxyl groups in H1 and H2B histones. Both protein kinases reacted with Ser-38 in H1 histone. With H2B histone as substrate protein kinase A phosphorylated Ser-32 as well as Ser-36, whereas protein kinase G reacted preferentially with Ser-32 and the reaction with Ser-36 was very slow. H3 and H4 histones were practically inactive substrates for protein kinase G. Although H2A histone has not been analyzed, the evidence has raised a possibility that protein kinase G utilizes a portion of the substrate proteins for protein kinase A.", "contents": "Studies on the sites in histones phosphorylated by adenosine 3':5'-monophosphate-dependent and guanosine 3':5'-monophosphate-dependent protein kinases. Adenosine 3':5'-monophosphate-dependent protein kinase (protein kinase A) purified from silkworm pupae phosphorylated five major fractions of calf thymus histone, whereas guanosine 3':5'-monophosphate-dependent protein kinase (protein kinase G) purified from the same organism reacted preferentially with H1, H2A, and H2B histones. Amino acid analysis of the phosphopeptides which were obtained by proteolytic digestion revealed that both protein kinases A and G showed the abilities to phosphorylate the same serine hydroxyl groups in H1 and H2B histones. Both protein kinases reacted with Ser-38 in H1 histone. With H2B histone as substrate protein kinase A phosphorylated Ser-32 as well as Ser-36, whereas protein kinase G reacted preferentially with Ser-32 and the reaction with Ser-36 was very slow. H3 and H4 histones were practically inactive substrates for protein kinase G. Although H2A histone has not been analyzed, the evidence has raised a possibility that protein kinase G utilizes a portion of the substrate proteins for protein kinase A."}
{"id": "PMID:185208", "title": "Inactivation of porcine heart cytoplasmic malate dehydrogenase by pyridoxal 5'-phosphate.", "content": "Pyridoxal 5'-phosphate (pyridoxal-5'-P) has been found to act as a bifunctional reagent during the inactivation of porcine heart cytoplasmic malate dehydrogenase (L-malate: NAD+ oxidoreductase, EC 1.1.1.37). The biphasic kinetics and X-azolidine-like structure formed were similar to those observed for mitochondrial malate dehydrogenase (Wimmer, M.J., Mo, T., Sawyers, D.L., and Harrison, J.H. (1975) J. Biol. Chem. 250, 710-715). In the cytoplasmic enzyme, however, irreversible inactivation representing X-azolidine formation was found to be the dominant characteristic of the interaction with pyridoxal-5'-P. Spectral evidence indicated that at total inactivation 2 mol of pyridoxal-5'-P were incorporated per mol of enzyme or one pyridoxal-5'-P per enzymatic active site. The presence of NADH protected the enzyme from inactivation suggesting interaction of pyridoxal-5'-P at or near the enzymatic active centers of this enzyme. Fluorometric titrations indicated that pyridoxal-5'-P-inactivated enzyme failed to bind NADH or at least failed to bind NADH in the same fashion as native enzyme.", "contents": "Inactivation of porcine heart cytoplasmic malate dehydrogenase by pyridoxal 5'-phosphate. Pyridoxal 5'-phosphate (pyridoxal-5'-P) has been found to act as a bifunctional reagent during the inactivation of porcine heart cytoplasmic malate dehydrogenase (L-malate: NAD+ oxidoreductase, EC 1.1.1.37). The biphasic kinetics and X-azolidine-like structure formed were similar to those observed for mitochondrial malate dehydrogenase (Wimmer, M.J., Mo, T., Sawyers, D.L., and Harrison, J.H. (1975) J. Biol. Chem. 250, 710-715). In the cytoplasmic enzyme, however, irreversible inactivation representing X-azolidine formation was found to be the dominant characteristic of the interaction with pyridoxal-5'-P. Spectral evidence indicated that at total inactivation 2 mol of pyridoxal-5'-P were incorporated per mol of enzyme or one pyridoxal-5'-P per enzymatic active site. The presence of NADH protected the enzyme from inactivation suggesting interaction of pyridoxal-5'-P at or near the enzymatic active centers of this enzyme. Fluorometric titrations indicated that pyridoxal-5'-P-inactivated enzyme failed to bind NADH or at least failed to bind NADH in the same fashion as native enzyme."}
{"id": "PMID:185209", "title": "Quantitative aspects of the conversion of 5 beta-cholestane intermediates to bile acids in man.", "content": "The in vivo conversion of several 5 beta-cholestane intermediates to primary bile acids was investigated in three patients with total biliary diversion. The following compounds were administered intravenously: 5 beta-[G-3H]-cholestane-3 alpha, 7 alpha-diol, 5 beta-[G-3H]cholestane-3 alpha, 7alpha, 26-triol, and 5 beta-[24-14C]cholestane-3 alpha, 7 alpha-25-triol. Bile was then collected quantitatively at frequent intervals for the next 21 to 28 h. The administered 5 beta-[G-3H]cholestane-3alpha, 7alpha, 26-triol was found to be efficiently converted to cholic and chenodeoxycholic acids in two patients; 61 and 75% of the administered label was found in primary bile acids. The proportion of labeled cholic to chenodeoxycholic acid was 1.20 and 1.02 in the bile of these patients, indicating that the C-26 triol was efficiently converted to cholic acid. The ratio of cholic to chenodeoxycholic acid (mass) in the bile of these patients was 1.23 and 2.32. The 5 beta-cholestane-3alpha, 7alpha-diol intermediate was also efficiently converted (71%) to both primary bile acids. The cholic to chenodeoxycholic acid ratios by mass and label were similar (2.97 versus 2.23). By contrast, the 5beta-cholestane-3alpha, 7alpha, 25-triol was poorly converted to bile acids in three patients. Following the administration of this compound almost all of the administered radioactivity found in the bile acid fraction was in cholic acid (5 to 19%) and very little (less than 5%) was found in chenodeoxycholic acid. These findings indicate that ring hydroxylation at position 12 is not materially hindered by the presence of a hydroxyl group on the side chain at C-26 in patients with biliary diversion. The labeled C-26-triol which was efficiently converted to both primary bile acids in a proportion similar to that which was observed for the bile acids synthesized by the liver suggests that this 5beta-cholestane derivative may be a major intermediate in the synthesis of both cholic and chenodeoxycholic acids.", "contents": "Quantitative aspects of the conversion of 5 beta-cholestane intermediates to bile acids in man. The in vivo conversion of several 5 beta-cholestane intermediates to primary bile acids was investigated in three patients with total biliary diversion. The following compounds were administered intravenously: 5 beta-[G-3H]-cholestane-3 alpha, 7 alpha-diol, 5 beta-[G-3H]cholestane-3 alpha, 7alpha, 26-triol, and 5 beta-[24-14C]cholestane-3 alpha, 7 alpha-25-triol. Bile was then collected quantitatively at frequent intervals for the next 21 to 28 h. The administered 5 beta-[G-3H]cholestane-3alpha, 7alpha, 26-triol was found to be efficiently converted to cholic and chenodeoxycholic acids in two patients; 61 and 75% of the administered label was found in primary bile acids. The proportion of labeled cholic to chenodeoxycholic acid was 1.20 and 1.02 in the bile of these patients, indicating that the C-26 triol was efficiently converted to cholic acid. The ratio of cholic to chenodeoxycholic acid (mass) in the bile of these patients was 1.23 and 2.32. The 5 beta-cholestane-3alpha, 7alpha-diol intermediate was also efficiently converted (71%) to both primary bile acids. The cholic to chenodeoxycholic acid ratios by mass and label were similar (2.97 versus 2.23). By contrast, the 5beta-cholestane-3alpha, 7alpha, 25-triol was poorly converted to bile acids in three patients. Following the administration of this compound almost all of the administered radioactivity found in the bile acid fraction was in cholic acid (5 to 19%) and very little (less than 5%) was found in chenodeoxycholic acid. These findings indicate that ring hydroxylation at position 12 is not materially hindered by the presence of a hydroxyl group on the side chain at C-26 in patients with biliary diversion. The labeled C-26-triol which was efficiently converted to both primary bile acids in a proportion similar to that which was observed for the bile acids synthesized by the liver suggests that this 5beta-cholestane derivative may be a major intermediate in the synthesis of both cholic and chenodeoxycholic acids."}
{"id": "PMID:185210", "title": "Yeast cytochrome c messenger RNA. In vitro translation and specific immunoprecipitation of the CYC1 gene product.", "content": "An assay based upon indirect immunoprecipitation has been developed for yeast cytochrome c and apocytochrome c. The specificity of this assay was demonstrated by its ability to selectively precipitate cytochrome c from an autolysate of yeast cell proteins. Translation of the polypeptide chain of cytochrome c in a wheat germ extract programmed with yeast poly(A) RNA was demonstrated using this immunoprecipitation assay. Translation of poly(A) RNA from yeast strains carrying nonsense mutations in the cyc1 gene yielded in vitro cytochrome c polypeptides which were shorter than the wild type protein by the amount expected for polypeptide chains which had terminated at the nonsense codon. The in vivo rate of cytochrome c synthesis was shown to be 6-fold greater in derepressed cells than in glucose-repressed cells. The 6-fold difference is sufficient to account for the 6-fold higher level of cytochrome c in derepressed than in repressed cells. The level of translatable cytochrome c mRNA is at least 4 times as high in derepressed as in glucose-repressed cells, suggesting that regulation occurs at some step in the synthesis of this messenger.", "contents": "Yeast cytochrome c messenger RNA. In vitro translation and specific immunoprecipitation of the CYC1 gene product. An assay based upon indirect immunoprecipitation has been developed for yeast cytochrome c and apocytochrome c. The specificity of this assay was demonstrated by its ability to selectively precipitate cytochrome c from an autolysate of yeast cell proteins. Translation of the polypeptide chain of cytochrome c in a wheat germ extract programmed with yeast poly(A) RNA was demonstrated using this immunoprecipitation assay. Translation of poly(A) RNA from yeast strains carrying nonsense mutations in the cyc1 gene yielded in vitro cytochrome c polypeptides which were shorter than the wild type protein by the amount expected for polypeptide chains which had terminated at the nonsense codon. The in vivo rate of cytochrome c synthesis was shown to be 6-fold greater in derepressed cells than in glucose-repressed cells. The 6-fold difference is sufficient to account for the 6-fold higher level of cytochrome c in derepressed than in repressed cells. The level of translatable cytochrome c mRNA is at least 4 times as high in derepressed as in glucose-repressed cells, suggesting that regulation occurs at some step in the synthesis of this messenger."}
{"id": "PMID:185211", "title": "Calcium and magnesium regulation of phosphorylation by ATP and ITP in sarcoplasmic reticulum vesicles.", "content": "Membrane phosphorylation and nucleoside triphosphatase activity of sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle were studied using ATP and ITP as substrates. The Ca2+ concentration was varied over a range large enough to saturate either the high affinity Ca2+-binding site or both high and low affinity binding sites. In intact vesicles, which are able to accumulate Ca2+, the steady state level of enzyme phosphorylated by either ATP or ITP is already high in 0.02 mM Ca2+ and does not vary as the Ca2+ concentration is increased to 10 mM. Essentially the same pattern of membrane phosphorylation by ATP is observed when leaky vesicles, which are unable to accumulate Ca2+, are used. However, for leaky vesicles, when ITP is used as substrate, the phosphoenzyme level increases 3- to 4-fold when the Ca2+ concentration is raised from 0.02 to 20 mM. When Mg2+ is omitted from the assay medum, the degree of membrane phosphorylation by ATP varies with Ca2+ in the same way as when ITP is used in the presence of Mg2+. Membrane phosphorylation of leaky vesicles by either ATP or ITP is observed in the absence of added Mg2+. When these vesicles are incubated in media containing ITP and 0.1 mM Ca2+, addition of Mg2+ up to 10 mM simultaneously decreases the steady state level of phosphoenzyme and increases the rate of ITP hydrolysis. When ATP is used, the addition of 10 mM Mg2+ increases both the steady state level of phosphoenzyme and the rate of ATP hydrolysis. When the Ca2+ concentration is raised to 10 or 20 mM, the degree of membrane phosphorylation by either ATP or ITP is maximal even in the absence of added Mg2+ and does not vary with the addition of 10 mM Mg2+. In these conditions the ATPase and ITPase activities are activated by Mg2+, although not to the level observed in 0.1 mM Ca2+. An excess of Mg2+ inhibits both the rate of hydrolysis and membrane phosphorylation by either ATP or ITP.", "contents": "Calcium and magnesium regulation of phosphorylation by ATP and ITP in sarcoplasmic reticulum vesicles. Membrane phosphorylation and nucleoside triphosphatase activity of sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle were studied using ATP and ITP as substrates. The Ca2+ concentration was varied over a range large enough to saturate either the high affinity Ca2+-binding site or both high and low affinity binding sites. In intact vesicles, which are able to accumulate Ca2+, the steady state level of enzyme phosphorylated by either ATP or ITP is already high in 0.02 mM Ca2+ and does not vary as the Ca2+ concentration is increased to 10 mM. Essentially the same pattern of membrane phosphorylation by ATP is observed when leaky vesicles, which are unable to accumulate Ca2+, are used. However, for leaky vesicles, when ITP is used as substrate, the phosphoenzyme level increases 3- to 4-fold when the Ca2+ concentration is raised from 0.02 to 20 mM. When Mg2+ is omitted from the assay medum, the degree of membrane phosphorylation by ATP varies with Ca2+ in the same way as when ITP is used in the presence of Mg2+. Membrane phosphorylation of leaky vesicles by either ATP or ITP is observed in the absence of added Mg2+. When these vesicles are incubated in media containing ITP and 0.1 mM Ca2+, addition of Mg2+ up to 10 mM simultaneously decreases the steady state level of phosphoenzyme and increases the rate of ITP hydrolysis. When ATP is used, the addition of 10 mM Mg2+ increases both the steady state level of phosphoenzyme and the rate of ATP hydrolysis. When the Ca2+ concentration is raised to 10 or 20 mM, the degree of membrane phosphorylation by either ATP or ITP is maximal even in the absence of added Mg2+ and does not vary with the addition of 10 mM Mg2+. In these conditions the ATPase and ITPase activities are activated by Mg2+, although not to the level observed in 0.1 mM Ca2+. An excess of Mg2+ inhibits both the rate of hydrolysis and membrane phosphorylation by either ATP or ITP."}
{"id": "PMID:185212", "title": "In vitro partial relipidation of apolipoproteins in plasma.", "content": "In vitro recombination of lipids with apolipoproteins is achieved when a concentrated solution of plasma lipids in petroleum ether is mixed with delipidated plasma. Combination of phospholipids and unesterified fatty acids are observed in amounts comparable with those originally present in the native unextracted plasma; triglycerides combine partially and cholesterol only slightly. On agarose gel immunoelectrophoresis, a component in the delipidated plasma which is reactive with high density lipoprotein antibodies migrates more slowly than high density lipoprotein in the undelipidated control plasma. However, the component reacting with low density lipoprotein antibodies in the delipidated plasma moves more rapidly than low density lipoprotein in the native plasma. These changes are reversed by recombination of lipid with delipidated plasma. All lipids present in the plasma phase after relipidation travel with the lipoproteins during zonal electrophoresis. The apparent concentrations of proteins reacting with high density and low density lipoprotein antibodies decrease when no lipid is present in plasma on assay by single radial immunodiffusion and immunoelectrophoresis, using commercially available lipoprotein antibodies. On relipidation, full immunochemical properties of high density lipoprotein are restored, but relipidated low density lipoprotein exhibits only partial immunochemical restoration.", "contents": "In vitro partial relipidation of apolipoproteins in plasma. In vitro recombination of lipids with apolipoproteins is achieved when a concentrated solution of plasma lipids in petroleum ether is mixed with delipidated plasma. Combination of phospholipids and unesterified fatty acids are observed in amounts comparable with those originally present in the native unextracted plasma; triglycerides combine partially and cholesterol only slightly. On agarose gel immunoelectrophoresis, a component in the delipidated plasma which is reactive with high density lipoprotein antibodies migrates more slowly than high density lipoprotein in the undelipidated control plasma. However, the component reacting with low density lipoprotein antibodies in the delipidated plasma moves more rapidly than low density lipoprotein in the native plasma. These changes are reversed by recombination of lipid with delipidated plasma. All lipids present in the plasma phase after relipidation travel with the lipoproteins during zonal electrophoresis. The apparent concentrations of proteins reacting with high density and low density lipoprotein antibodies decrease when no lipid is present in plasma on assay by single radial immunodiffusion and immunoelectrophoresis, using commercially available lipoprotein antibodies. On relipidation, full immunochemical properties of high density lipoprotein are restored, but relipidated low density lipoprotein exhibits only partial immunochemical restoration."}
{"id": "PMID:185213", "title": "Superoxide anion as a mediator of drug-induced oxidative hemolysis.", "content": "The superoxide dismutase inhibitor diethyldithiocarbamate (DDC) was utilized to study the toxic effect of 1,4-naphthoquinone 2-sulfonate (NQ), a structural analog of the hemolytic drug, menadione, on red cells. NQ was shown to react with hemoglobin and result in the generation of superoxide anion (O2-). Red cells treated with NQ were found to undergo a gradual disappearance of their oxyhemoglobin and also hemolyze. Red cells pretreated with DDC to inhibit cellular superoxide dismutase were found to be markedly sensitive to oxyhemoglobin destruction and hemolysis in the presence of NQ. Superoxide dismutase-inhibited red cells were also found to undergo a slow autohemolysis in the absence of NQ. No evidence for lipid peroxidation was obtained for red cells treated with NQ either in the presence or the absence of DDC. Ghosts prepared from superoxide dismutase-inhibited red cells exposed to NQ were found to retain a green hemoglobin-derived pigment.", "contents": "Superoxide anion as a mediator of drug-induced oxidative hemolysis. The superoxide dismutase inhibitor diethyldithiocarbamate (DDC) was utilized to study the toxic effect of 1,4-naphthoquinone 2-sulfonate (NQ), a structural analog of the hemolytic drug, menadione, on red cells. NQ was shown to react with hemoglobin and result in the generation of superoxide anion (O2-). Red cells treated with NQ were found to undergo a gradual disappearance of their oxyhemoglobin and also hemolyze. Red cells pretreated with DDC to inhibit cellular superoxide dismutase were found to be markedly sensitive to oxyhemoglobin destruction and hemolysis in the presence of NQ. Superoxide dismutase-inhibited red cells were also found to undergo a slow autohemolysis in the absence of NQ. No evidence for lipid peroxidation was obtained for red cells treated with NQ either in the presence or the absence of DDC. Ghosts prepared from superoxide dismutase-inhibited red cells exposed to NQ were found to retain a green hemoglobin-derived pigment."}
{"id": "PMID:185214", "title": "Phosphorylation in vitro of eukaryotic initiation factors IF-E2 and IF-E3 by protein kinases.", "content": "Purified protein synthesis initiation factors IF-E2 and IF-E3 from rabbit reticulocytes were phosphorylated in vitro with protein kinases isolated from the same source. The highest levels of phosphorylation resulted from incubation of the factors with a cyclic nucleotide-independent protein kinase previously shown to have specificity for acidic proteins. The extent of phosphorylation of initiation factor IF-E2 was between 0.3 and 0.4 mol of phosphate per mol of factor complex, with either ATP or GTP as phosphoryl donor. Initiation factor IF-E2 is composed of three nonidentical polypeptides; only the polypeptide with a molecular weight of 52,000 was phosphorylated. The extent of phosphorylation of initiation factor IF-E3 was between 0.7 and 1.0 mol of phosphate per mol of factor complex with GTP as phosphoryl donor; with ATP, less phosphorylation of the factor was obtained. Initiation factor IF-E3 is composed of 9 to 11 nonidentical polypeptides; only 2 of these, with molecular weights of 120,000 and 70,000, were phosphorylated. A lower level of phosphorylation of initiation factor IF-E3 was found with the cyclic AMP-dependent protein kinase; the polypeptide of molecular weight 140,000 was the major site of phosphorylation.", "contents": "Phosphorylation in vitro of eukaryotic initiation factors IF-E2 and IF-E3 by protein kinases. Purified protein synthesis initiation factors IF-E2 and IF-E3 from rabbit reticulocytes were phosphorylated in vitro with protein kinases isolated from the same source. The highest levels of phosphorylation resulted from incubation of the factors with a cyclic nucleotide-independent protein kinase previously shown to have specificity for acidic proteins. The extent of phosphorylation of initiation factor IF-E2 was between 0.3 and 0.4 mol of phosphate per mol of factor complex, with either ATP or GTP as phosphoryl donor. Initiation factor IF-E2 is composed of three nonidentical polypeptides; only the polypeptide with a molecular weight of 52,000 was phosphorylated. The extent of phosphorylation of initiation factor IF-E3 was between 0.7 and 1.0 mol of phosphate per mol of factor complex with GTP as phosphoryl donor; with ATP, less phosphorylation of the factor was obtained. Initiation factor IF-E3 is composed of 9 to 11 nonidentical polypeptides; only 2 of these, with molecular weights of 120,000 and 70,000, were phosphorylated. A lower level of phosphorylation of initiation factor IF-E3 was found with the cyclic AMP-dependent protein kinase; the polypeptide of molecular weight 140,000 was the major site of phosphorylation."}
{"id": "PMID:185215", "title": "Induction of refractoriness to thyrotropin stimulation in cultured thyroid cells. Dependence on new protein synthesis.", "content": "Cultured dog thyroid cells were used to investigate the mechanism by which previous exposure to thyrotropin (TSH) induces refractoriness to further TSH stimulation of cellular adenosine 3'-5'-monophosphate (cAMP). Refractoriness of the cAMP response to TSH could not be overcome by exposure of the cells to supramaximal stimulatory concentrations of TSH. Although an unknown factor present in human and fetal calf serum was found to inhibit the thyroid cell cAMP response to TSH, this factor could not account for refractoriness because refractoriness could be induced in the absence of serum. Induction of thyroid refractoriness did not appear to be related to cellular concentrations of cyclic AMP, because equal refractoriness was produced by TSH alone or TSH plus the phosphodiesterase inhibitor, 3-isobutyl-1-methyl xanthine. In addition, preincubation of thyroid cells in 10(-4) M cAMP did not result in subsequent refractoriness. Recovery from the refractory process required almost 24 h. Short term (15 min) stimulation with TSH did not produce thyroid cell refractoriness, and reversal of the stimulation was obtained by thorough washing of the cells. Long term TSH stimulation (16 h), however, resulted in both supramaximal cAMP response to TSH, and inclusion of TSH together with cycloheximide did not produce refractoriness. Cyclic AMP phosphodiesterase activity in thyroid cell homogenate was unaltered by TSH or dibutyryl cyclic AMP pretreatment of the cells for up to 24 h, or cycloheximide for up to 4 h. In contrast, TSH-stimulated, but not F--stimulated, adenylate cyclase activity was reduced in thyroid cell homogenates after preincubation of the cells in TSH. Refractoriness to TSH stimulation was not associated with an alteration in the binding of 125I-TSH to cultured thyroid cells. These studies suggest that the thyroid cAMP response to TSH is modulated by an inhibitory mechanism dependent upon new protein synthesis. TSH stimulation itself increases the degree of this inhibition through a mechanism not involving cAMP.", "contents": "Induction of refractoriness to thyrotropin stimulation in cultured thyroid cells. Dependence on new protein synthesis. Cultured dog thyroid cells were used to investigate the mechanism by which previous exposure to thyrotropin (TSH) induces refractoriness to further TSH stimulation of cellular adenosine 3'-5'-monophosphate (cAMP). Refractoriness of the cAMP response to TSH could not be overcome by exposure of the cells to supramaximal stimulatory concentrations of TSH. Although an unknown factor present in human and fetal calf serum was found to inhibit the thyroid cell cAMP response to TSH, this factor could not account for refractoriness because refractoriness could be induced in the absence of serum. Induction of thyroid refractoriness did not appear to be related to cellular concentrations of cyclic AMP, because equal refractoriness was produced by TSH alone or TSH plus the phosphodiesterase inhibitor, 3-isobutyl-1-methyl xanthine. In addition, preincubation of thyroid cells in 10(-4) M cAMP did not result in subsequent refractoriness. Recovery from the refractory process required almost 24 h. Short term (15 min) stimulation with TSH did not produce thyroid cell refractoriness, and reversal of the stimulation was obtained by thorough washing of the cells. Long term TSH stimulation (16 h), however, resulted in both supramaximal cAMP response to TSH, and inclusion of TSH together with cycloheximide did not produce refractoriness. Cyclic AMP phosphodiesterase activity in thyroid cell homogenate was unaltered by TSH or dibutyryl cyclic AMP pretreatment of the cells for up to 24 h, or cycloheximide for up to 4 h. In contrast, TSH-stimulated, but not F--stimulated, adenylate cyclase activity was reduced in thyroid cell homogenates after preincubation of the cells in TSH. Refractoriness to TSH stimulation was not associated with an alteration in the binding of 125I-TSH to cultured thyroid cells. These studies suggest that the thyroid cAMP response to TSH is modulated by an inhibitory mechanism dependent upon new protein synthesis. TSH stimulation itself increases the degree of this inhibition through a mechanism not involving cAMP."}
{"id": "PMID:185216", "title": "Insulin stimulation of heart glycogen synthase D phosphatase (protein phosphatase).", "content": "Insulin rapidly produced an increase in per cent of total heart glycogen synthase in the I form in fed rats. In fasted rats the response was diminished and delayed. In diabetic animals there was no response over the 15-min time period studied. Since synthase phosphatase activity is necessary for synthase D to I conversion, the phosphatase activity was determined in extracts from these groups of animals. In the fasted and diabetic rats phosphatase activity was less than one-half of that in fed animals. Administration of insulin to fasting animals increased synthase phosphatase activity to a level approaching that of fed animals by 15 min. In diabetic animals insulin also stimulated an increase in synthase phosphatase activity but 30 min were required for full activation. Insulin had no effect in normal fed animals. Insulin activation of synthase phosphatase activity in heart extracts from fasted animals was still present after Sephadex G-25 chromatography and ammonium sulfate precipitation. Thus insulin had induced a stable modification of the phosphatase itself or of its substrate synthase D rendering the latter a more favorable substrate for the reaction. A difference in sensitivity of the reaction to glycogen inhibition was present between fed and fasted animals. Increasing concentrations of glycogen had only a slight inhibitory effect in extracts from fed animals but considerably reduced activity in extracts from fasted animals. Insulin administration reduced the sensitivity of the phosphatase reaction to glycogen inhibition. This could explain, at least in part, the increased phosphatase activity noted in the insulin-treated, fasted rats since glycogen was routinely added to the homogenizing buffer.", "contents": "Insulin stimulation of heart glycogen synthase D phosphatase (protein phosphatase). Insulin rapidly produced an increase in per cent of total heart glycogen synthase in the I form in fed rats. In fasted rats the response was diminished and delayed. In diabetic animals there was no response over the 15-min time period studied. Since synthase phosphatase activity is necessary for synthase D to I conversion, the phosphatase activity was determined in extracts from these groups of animals. In the fasted and diabetic rats phosphatase activity was less than one-half of that in fed animals. Administration of insulin to fasting animals increased synthase phosphatase activity to a level approaching that of fed animals by 15 min. In diabetic animals insulin also stimulated an increase in synthase phosphatase activity but 30 min were required for full activation. Insulin had no effect in normal fed animals. Insulin activation of synthase phosphatase activity in heart extracts from fasted animals was still present after Sephadex G-25 chromatography and ammonium sulfate precipitation. Thus insulin had induced a stable modification of the phosphatase itself or of its substrate synthase D rendering the latter a more favorable substrate for the reaction. A difference in sensitivity of the reaction to glycogen inhibition was present between fed and fasted animals. Increasing concentrations of glycogen had only a slight inhibitory effect in extracts from fed animals but considerably reduced activity in extracts from fasted animals. Insulin administration reduced the sensitivity of the phosphatase reaction to glycogen inhibition. This could explain, at least in part, the increased phosphatase activity noted in the insulin-treated, fasted rats since glycogen was routinely added to the homogenizing buffer."}
{"id": "PMID:185217", "title": "2-Fluoroadenosine 3':5'-monophosphate. A metabolite of 2-fluoroadenosine in mouse cytotoxic lymphocytes.", "content": "2-Fluoroadenosine (F-Ado) is a potent inhibitor of lymphocyte-mediated cytolysis studied in vitro. The inhibition of cytolysis by F-Ado was potentiated markedly by an inhibiotr (Ro 20-1724) of adenosine 3':5'-monophosphate (cAMP) phosphodiesterase and, unlike the inhibition caused by adenosine, was irreversible when the cytotoxic lymphocytes were incubated with F-Ado and were then washed free of exogenous nucleoside. Incubation of cytotoxic lymphocytes with F-Ado resulted in the rapid, dose-dependent formation of 2-fluoroadenosine 5'-triphosphate (F-ATP); the build-up of F-ATP within these cells was accompanied by a reciprocal depletion of ATP. Once formed intracellularly, the F-ATP was not diminished during a subsequent 30-min incubation of the cells in F-Ado-free medium. 2-Fluoroadenosine 3':5'-monophosphate (F-cAMP), a novel compound, was synthesized chemically. This cAMP analogue was found to be highly cross-reactive in a radioimmunoassay specific for cAMP and to be equipotent to cAMP in its ability to activate a crude preparation of protein kinase derived from rat brain. A column chromatographic procedure was devised whereby F-cAMP and cAMP could be purified simultaneously from tissue extracts. Treatment of cytotoxic lymphocytes with F-Ado resulted in the formation of presumptive F-cAMP in amounts greater than that of cAMP, as determined by the concentration of F-Ado added to the medium and was not observed when the lymphocytes were incubated with either adenosine or 2-chloroadenosine, two agents which caused large increases in cAMP. The simultaneous presence of Ro 20-1724 enhances greatly the formation of F-cAMP from F-Ado without affecting the pool size of F-ATP. Removal of exogenous F-Ado from cells previously incubated with this drug and subsequent incubation of these cells in drug-free medium did not result in a substantial reduction in intracellular F-Ado (via prior incubation with F-Ado); 2'-deoxyadenosine was also effective in this capacity, while 9-beta-D-arabinofulanosyladenine was without effect. The level of cAMP was elevated transiently, in a dose-dependent manner, by F-Ado, and returned to control value after removal of exogenous F-Ado from the cells. Ro 20-1724 enhanced greatly this transient elevation of cAMP caused by F-Ado.", "contents": "2-Fluoroadenosine 3':5'-monophosphate. A metabolite of 2-fluoroadenosine in mouse cytotoxic lymphocytes. 2-Fluoroadenosine (F-Ado) is a potent inhibitor of lymphocyte-mediated cytolysis studied in vitro. The inhibition of cytolysis by F-Ado was potentiated markedly by an inhibiotr (Ro 20-1724) of adenosine 3':5'-monophosphate (cAMP) phosphodiesterase and, unlike the inhibition caused by adenosine, was irreversible when the cytotoxic lymphocytes were incubated with F-Ado and were then washed free of exogenous nucleoside. Incubation of cytotoxic lymphocytes with F-Ado resulted in the rapid, dose-dependent formation of 2-fluoroadenosine 5'-triphosphate (F-ATP); the build-up of F-ATP within these cells was accompanied by a reciprocal depletion of ATP. Once formed intracellularly, the F-ATP was not diminished during a subsequent 30-min incubation of the cells in F-Ado-free medium. 2-Fluoroadenosine 3':5'-monophosphate (F-cAMP), a novel compound, was synthesized chemically. This cAMP analogue was found to be highly cross-reactive in a radioimmunoassay specific for cAMP and to be equipotent to cAMP in its ability to activate a crude preparation of protein kinase derived from rat brain. A column chromatographic procedure was devised whereby F-cAMP and cAMP could be purified simultaneously from tissue extracts. Treatment of cytotoxic lymphocytes with F-Ado resulted in the formation of presumptive F-cAMP in amounts greater than that of cAMP, as determined by the concentration of F-Ado added to the medium and was not observed when the lymphocytes were incubated with either adenosine or 2-chloroadenosine, two agents which caused large increases in cAMP. The simultaneous presence of Ro 20-1724 enhances greatly the formation of F-cAMP from F-Ado without affecting the pool size of F-ATP. Removal of exogenous F-Ado from cells previously incubated with this drug and subsequent incubation of these cells in drug-free medium did not result in a substantial reduction in intracellular F-Ado (via prior incubation with F-Ado); 2'-deoxyadenosine was also effective in this capacity, while 9-beta-D-arabinofulanosyladenine was without effect. The level of cAMP was elevated transiently, in a dose-dependent manner, by F-Ado, and returned to control value after removal of exogenous F-Ado from the cells. Ro 20-1724 enhanced greatly this transient elevation of cAMP caused by F-Ado."}
{"id": "PMID:185218", "title": "Escherichia coli acetate kinase mechanism studied by net initial rate, equilibrium, and independent isotopic exchange kinetics.", "content": "The equilibrium constant of the reaction catalyzed by acetate kinase (E.C. 2.7.2.1.) was determined: K = (MgADP) (acetylphosphate)/(MgATP)(acetate) = 6.7 +/- 1.3 X 10 (-4) (pH 7.4, 25 degrees). The respective free nucleotides uncomplexed to magnesium inhibit the net reaction in both directions: competitively with the respective magnesium nucleotide (MgATP or MgADP) and noncompetitively with the co-substrate (acetate or acetylphosphate). Excess free magnesium also inhibits the net reaction in both directions. The inhibition is not competitive with the phosphoryl donor (MgATP or acetylphosphate) but is competitive with respect to the phosphoryl acceptor (acetate or MgADP). A 50-fold increase in concentration of reactants at equilibrium in 0.1 M Tris/HCl, pH 7.4, at 25 degrees resulted in a rise to plateau levels of the acetate equilibrium acetylphosphate exchange rate (measured with [U-14C]acetate) and of the ATP equilibrium ADP exchange rate (measured with [U-14C]ADP and 10-fold higher than acetate equilibrium acetylphosphate), suggesting that there is no compulsory order of binding of magnesium nucleotide and co-substrate and that all chemical transformation steps cannot be much slower than the dissociation steps. The ATP equilibrium ADP exchange rate was independent of the presence or concentration of co-substrate, whereas the acetate equilibrium acetylphosphate exchange reaction occurred only in the presence of magnesium nucleotide, and the rate was directly related to the degree of saturation of enzyme with magnesium nucleotide. The independent ATP equilibrium ADP exchange, which presumably involves a phosphoenzyme intermediate, was progressively inhibited by increasingly elevated MgADP concentrations (when MgADP/MgATP greater than or equal 5), but increasing MgATP/MgADP was not inhibitory, suggesting that MgADP may bind to nonphosphorylated as well as phosphorylated enzyme, but that MgATP cannot bind to phosphorylated enzyme. While direct transfer of the phosphoryl group between nucleotide and co-substrate in a concerted mechanism has not been ruled out, an \"activated ping pong\" mechanism can also be proposed which is compatible with the isotopic exchange and initial net rate kinetic results. This mechanism includes a phosphoenzyme intermediate and requires enzyme-bount MgADP for phosphorylation of the enzyme by acetylphosphate.", "contents": "Escherichia coli acetate kinase mechanism studied by net initial rate, equilibrium, and independent isotopic exchange kinetics. The equilibrium constant of the reaction catalyzed by acetate kinase (E.C. 2.7.2.1.) was determined: K = (MgADP) (acetylphosphate)/(MgATP)(acetate) = 6.7 +/- 1.3 X 10 (-4) (pH 7.4, 25 degrees). The respective free nucleotides uncomplexed to magnesium inhibit the net reaction in both directions: competitively with the respective magnesium nucleotide (MgATP or MgADP) and noncompetitively with the co-substrate (acetate or acetylphosphate). Excess free magnesium also inhibits the net reaction in both directions. The inhibition is not competitive with the phosphoryl donor (MgATP or acetylphosphate) but is competitive with respect to the phosphoryl acceptor (acetate or MgADP). A 50-fold increase in concentration of reactants at equilibrium in 0.1 M Tris/HCl, pH 7.4, at 25 degrees resulted in a rise to plateau levels of the acetate equilibrium acetylphosphate exchange rate (measured with [U-14C]acetate) and of the ATP equilibrium ADP exchange rate (measured with [U-14C]ADP and 10-fold higher than acetate equilibrium acetylphosphate), suggesting that there is no compulsory order of binding of magnesium nucleotide and co-substrate and that all chemical transformation steps cannot be much slower than the dissociation steps. The ATP equilibrium ADP exchange rate was independent of the presence or concentration of co-substrate, whereas the acetate equilibrium acetylphosphate exchange reaction occurred only in the presence of magnesium nucleotide, and the rate was directly related to the degree of saturation of enzyme with magnesium nucleotide. The independent ATP equilibrium ADP exchange, which presumably involves a phosphoenzyme intermediate, was progressively inhibited by increasingly elevated MgADP concentrations (when MgADP/MgATP greater than or equal 5), but increasing MgATP/MgADP was not inhibitory, suggesting that MgADP may bind to nonphosphorylated as well as phosphorylated enzyme, but that MgATP cannot bind to phosphorylated enzyme. While direct transfer of the phosphoryl group between nucleotide and co-substrate in a concerted mechanism has not been ruled out, an \"activated ping pong\" mechanism can also be proposed which is compatible with the isotopic exchange and initial net rate kinetic results. This mechanism includes a phosphoenzyme intermediate and requires enzyme-bount MgADP for phosphorylation of the enzyme by acetylphosphate."}
{"id": "PMID:185219", "title": "8-Alkylaminoadenyl nucleotides as probes of dehydrogenase interactions with nucleotide analogs of different glycosyl conformation.", "content": "The nucleotides 8-amino-, 8-methylamino-, and 8-dimethylaminoadenylic acid have been synthesized and their preferred conformations about the glycosyl bond in qaueous solution have been determined by 1H nuclear magnetic resonance spectroscopy. Paramagnetic relaxation studies, nuclear Overhauser enhancement measurements, chemical shifts, and coupling constant comparisons indicate that their is rotation about the glycosyl bond and that preference for either the anti or syn conformation depends on the extent of alkyl substitution on the 8-amino group. The primary and secondary amines 8-amino- and 8-methylaminoadenylic acid adopt a perferential anti conformation about the glycosyl bond, while the tertiary amine 8-dimethylaminoadenylic acid exists predominantly in the syn form. These three analogs provide a system to study interactions of a dehydrogenase with coenzyme inhibitors having different glycosyl conformer populations. All three analogs are competitive inhibitors of NADH in reaction with chicken muscle lactate dehydrogenase, and the Ki values show little dependence on the nature of the amino substitution. This demonstrates that the distribution of conformations about the nucleotide glycosyl bond does not effect the competition of the nucleotide for lactate dehydrogenase apoenzyme. Several models for enzyme-coenzyme binding are discussed. The available data cannot distinguish whether the enzyme binds nucleotide in both the anti and syn conformations or in purely the anti conformation. However, at some stage of the enzyme-coenzyme interaction, there appears to be a strong stabilization of the nucleotide in the anti conformation about the glycosyl bond.", "contents": "8-Alkylaminoadenyl nucleotides as probes of dehydrogenase interactions with nucleotide analogs of different glycosyl conformation. The nucleotides 8-amino-, 8-methylamino-, and 8-dimethylaminoadenylic acid have been synthesized and their preferred conformations about the glycosyl bond in qaueous solution have been determined by 1H nuclear magnetic resonance spectroscopy. Paramagnetic relaxation studies, nuclear Overhauser enhancement measurements, chemical shifts, and coupling constant comparisons indicate that their is rotation about the glycosyl bond and that preference for either the anti or syn conformation depends on the extent of alkyl substitution on the 8-amino group. The primary and secondary amines 8-amino- and 8-methylaminoadenylic acid adopt a perferential anti conformation about the glycosyl bond, while the tertiary amine 8-dimethylaminoadenylic acid exists predominantly in the syn form. These three analogs provide a system to study interactions of a dehydrogenase with coenzyme inhibitors having different glycosyl conformer populations. All three analogs are competitive inhibitors of NADH in reaction with chicken muscle lactate dehydrogenase, and the Ki values show little dependence on the nature of the amino substitution. This demonstrates that the distribution of conformations about the nucleotide glycosyl bond does not effect the competition of the nucleotide for lactate dehydrogenase apoenzyme. Several models for enzyme-coenzyme binding are discussed. The available data cannot distinguish whether the enzyme binds nucleotide in both the anti and syn conformations or in purely the anti conformation. However, at some stage of the enzyme-coenzyme interaction, there appears to be a strong stabilization of the nucleotide in the anti conformation about the glycosyl bond."}
{"id": "PMID:185220", "title": "Incorporation of mitochondrial membrane proteins into liposomes containing acidic phospholipids.", "content": "Cytochrome oxidase, QH2-cytochrome c reductase, and the oligomycin-sensitive adenosine triphosphatase were incorporated into liposomes by a new procedure which yielded unidirectional orientation of the proteins. Cytochrome oxidase was reconstituted in the mitochrondrial orientation and the adenosine triphosphatase in the submitochondrial orientation. Reconstitutions were achieved by incubating the proteins at room temperature with liposomes which contained phosphatidylcholine, phosphatidylethanolamine, and an acidic phospholipid (cardiolipin, phosphatidylinositol, or phosphatidylserine). The incorporation occurred without added detergent or sonication. This incorporation procedure may serve as a model for the insertion of proteins in vivo.", "contents": "Incorporation of mitochondrial membrane proteins into liposomes containing acidic phospholipids. Cytochrome oxidase, QH2-cytochrome c reductase, and the oligomycin-sensitive adenosine triphosphatase were incorporated into liposomes by a new procedure which yielded unidirectional orientation of the proteins. Cytochrome oxidase was reconstituted in the mitochrondrial orientation and the adenosine triphosphatase in the submitochondrial orientation. Reconstitutions were achieved by incubating the proteins at room temperature with liposomes which contained phosphatidylcholine, phosphatidylethanolamine, and an acidic phospholipid (cardiolipin, phosphatidylinositol, or phosphatidylserine). The incorporation occurred without added detergent or sonication. This incorporation procedure may serve as a model for the insertion of proteins in vivo."}
{"id": "PMID:185221", "title": "Spin label studies on conformational changes of aphohemoglobin due to heme binding.", "content": "Human apohemoglobin (globin) was spin-labeled at the beta-93 sulfhydryl groups with 2,2,5,5-tetramethyl-3-aminopyrrolidine-I-oxyl. Spin-labeled globin exhibited an EPR spectra that is less immobilized than that of spin-labeled hemoglobin, indicating the conformational difference in the vicinity of the label between hemoglobin and globin. Spectrophotometric titration of spin-labeled globin with protohemin showed that 1 mol of globin (on the tetramer basis) combines with 4 mol of hemin, producing a holomethemoglobin spectrophotometrically indistinguishable from native methemoglobin. The EPR spectrum was also changed strikingly upon the addition of protohemin. This change, however, was not proportional to the amount of hemin added, but marked changes occurred after 3 to 4 mol of hemin were mixed with 1 mol of spin-labeled globin. The EPR spectrum of spin-labeled hemoglobin thus prepared was identical with that prepared by direct spin labeling to methemoglobin. These results suggest the preferential binding of hemin to alpha-globin chains in the course of heme binding by globin. This assumption was further confirmed by preparing spin-labeled semihemoglobin in which only one kind of chain contained hemin (alpha h betaO SL and alpha O beta h SL). The EPR spectrum of the alpha h beta O SL molecule showed a slightly immobilized EPR spectrum, similar to that of spin-labeled globin mixed with 50% of the stoichiometric amount of hemin. On the other hand, the alpha O beta h SL molecule showed a distinctly different EPR signal from that of globin half-saturated with hemin, and showed an intermediate spectrum between those of beta h SL and alpha h beta h SL. These results indicate that heme binding to globin chains brings about a major conformational change in the protein moiety and that chain-chain association plays a secondary role. We conclude that hemin binds preferentially to alpha-globin chains and that the conformation of globin changes rapidly to that of methemoglobin after all four hemes are attached to globin heme pockets.", "contents": "Spin label studies on conformational changes of aphohemoglobin due to heme binding. Human apohemoglobin (globin) was spin-labeled at the beta-93 sulfhydryl groups with 2,2,5,5-tetramethyl-3-aminopyrrolidine-I-oxyl. Spin-labeled globin exhibited an EPR spectra that is less immobilized than that of spin-labeled hemoglobin, indicating the conformational difference in the vicinity of the label between hemoglobin and globin. Spectrophotometric titration of spin-labeled globin with protohemin showed that 1 mol of globin (on the tetramer basis) combines with 4 mol of hemin, producing a holomethemoglobin spectrophotometrically indistinguishable from native methemoglobin. The EPR spectrum was also changed strikingly upon the addition of protohemin. This change, however, was not proportional to the amount of hemin added, but marked changes occurred after 3 to 4 mol of hemin were mixed with 1 mol of spin-labeled globin. The EPR spectrum of spin-labeled hemoglobin thus prepared was identical with that prepared by direct spin labeling to methemoglobin. These results suggest the preferential binding of hemin to alpha-globin chains in the course of heme binding by globin. This assumption was further confirmed by preparing spin-labeled semihemoglobin in which only one kind of chain contained hemin (alpha h betaO SL and alpha O beta h SL). The EPR spectrum of the alpha h beta O SL molecule showed a slightly immobilized EPR spectrum, similar to that of spin-labeled globin mixed with 50% of the stoichiometric amount of hemin. On the other hand, the alpha O beta h SL molecule showed a distinctly different EPR signal from that of globin half-saturated with hemin, and showed an intermediate spectrum between those of beta h SL and alpha h beta h SL. These results indicate that heme binding to globin chains brings about a major conformational change in the protein moiety and that chain-chain association plays a secondary role. We conclude that hemin binds preferentially to alpha-globin chains and that the conformation of globin changes rapidly to that of methemoglobin after all four hemes are attached to globin heme pockets."}
{"id": "PMID:185222", "title": "Cell surface receptors for insulin and human growth hormone. Effect of microtubule and microfilament modifiers.", "content": "The receptors for the polypeptide hormones, insulin and growth hormone, are located on the cell surface. Since the cytoplasmic microtubules and microfilaments are involved in the mobility and distribution of surface receptors for immunoglobulins and lectins, we investigated the role of these structures in the binding of insulin and human growth hormone to their receptors on cultured human lymphocytes (IM-9). Cells preincubated with microfilament modifiers, cytochalasin A, B, and D (10 mug/ml), had decreased binding of insulin (30%) and human growth hormone (60%) under steady state conditions, which was not reversed by removing the cytochalasins from the medium and was due entirely to a reduced number of receptor sites on the cell surfact. The lost receptors were not detected in the medium, suggesting a redistribution within the cell. The cytochalasins failed to alter the affinity of the hormones for their receptors or the negative cooperativity of the insulin receptor. The anti-microtubule agents (vincristine, vinblastine, colchicine) had no effect on the binding of insulin and growth hormone to their receptors. Deuterium oxide, a stabilizer of microtubules and other proteins, decreased the affinity (40%) of insulin for its receptors under steady state conditions and accelerated moderately the spontaneous dissociation of 125I-insulin from its receptors. Since cytochalasin decreases the number of available insulin and human growth hormone receptor sites, cytochalasin-sensitive microfilamentous structures appear to modulate the exposure of cell surface hormone receptors, while microtubules do not seem to be involved.", "contents": "Cell surface receptors for insulin and human growth hormone. Effect of microtubule and microfilament modifiers. The receptors for the polypeptide hormones, insulin and growth hormone, are located on the cell surface. Since the cytoplasmic microtubules and microfilaments are involved in the mobility and distribution of surface receptors for immunoglobulins and lectins, we investigated the role of these structures in the binding of insulin and human growth hormone to their receptors on cultured human lymphocytes (IM-9). Cells preincubated with microfilament modifiers, cytochalasin A, B, and D (10 mug/ml), had decreased binding of insulin (30%) and human growth hormone (60%) under steady state conditions, which was not reversed by removing the cytochalasins from the medium and was due entirely to a reduced number of receptor sites on the cell surfact. The lost receptors were not detected in the medium, suggesting a redistribution within the cell. The cytochalasins failed to alter the affinity of the hormones for their receptors or the negative cooperativity of the insulin receptor. The anti-microtubule agents (vincristine, vinblastine, colchicine) had no effect on the binding of insulin and growth hormone to their receptors. Deuterium oxide, a stabilizer of microtubules and other proteins, decreased the affinity (40%) of insulin for its receptors under steady state conditions and accelerated moderately the spontaneous dissociation of 125I-insulin from its receptors. Since cytochalasin decreases the number of available insulin and human growth hormone receptor sites, cytochalasin-sensitive microfilamentous structures appear to modulate the exposure of cell surface hormone receptors, while microtubules do not seem to be involved."}
{"id": "PMID:185224", "title": "In vitro epiphyseal-plate growth in various constant electrical fields.", "content": "An in vitro epiphyseal-plate model was subjected to various electrical fields. At a voltage gradient of 1500 volts per centimeter, a consistent, highly significant acceleration of growth of the epiphyseal plate occurred as measured from photomacrographs and as indicated by incorporation of 45Ca, 35S, and 3H-thymidine. The growth acceleration was due to voltage gradients and not to current flow. Although the mechanism of action of the electrical field is not known, it is obvious that the voltage gradient, either directly or indirectly, incites a physiological response of the growth-plate chondrocyte.", "contents": "In vitro epiphyseal-plate growth in various constant electrical fields. An in vitro epiphyseal-plate model was subjected to various electrical fields. At a voltage gradient of 1500 volts per centimeter, a consistent, highly significant acceleration of growth of the epiphyseal plate occurred as measured from photomacrographs and as indicated by incorporation of 45Ca, 35S, and 3H-thymidine. The growth acceleration was due to voltage gradients and not to current flow. Although the mechanism of action of the electrical field is not known, it is obvious that the voltage gradient, either directly or indirectly, incites a physiological response of the growth-plate chondrocyte."}
{"id": "PMID:185226", "title": "Ascorbate-independent proline hydroxylation resulting from viral transformation of Balb 3T3 cells and unaffected by dibutyryl cAMP treatment.", "content": "Collagen synthesis, hydroxylation of proline in collagen, and collagen secretion were studied in the contact-inhibited mouse fibroblast line, Balb 3T3; the Kirsten virus transformed line, Ki-3T3; and dibutyryl cAMP (dbcAMP)-treated Ki-3T3 cells, during the various phases of the growth cycle. Transformed cells in both logarithmic and stationary phase produced lower levels of collagen than the parent line but 85-90% of the theoretically possible hydroxyproline residues of the collagen were formed even when ascorbic acid was not added to the culture medium. Moreover, the transformed cells showed only about a 20% increase of collagen secretion upon addition of ascorbate. This was in contrast to the ascorbate requirement for maximal proline hydroxylation and the 2-3 fold stimulation of collagen secretion by ascorbate in the parent Balb 3T3 cells. Although dbcAMP treatment caused Ki-3T3 cells to assume a more normal morphology and increased the relative rate of collagen synthesis to levels similar to that of 3T3, such treatment did not restore an ascorbate requirement for proline hydroxylation or collagen secretion. The specific activity of the enzyme prolyl hydroxylase also was not affected by dbcAMP treatment although collagen synthesis was increased by such treatment. In addition, it was found that ascorbic acid was not effective in activating prolyl hydroxylase derived from Ki-3T3 or dbcAMP-treated Ki-3T3 cell cultures either in logarithmic phase or stationary phase. Ki-3T3 cultures did not accumulate ascorbic acid in cells or medium nor was ascorbic acid synthesized from the precursor 14C-glucuronate in cell homogenates. The results suggest that virally transformed Balb 3T3 cells acquire the capacity to synthesize a reducing cofactor for prolyl hydroxylase and that this function may be related to the increased glycolytic metabolism of these cells since neither cellular metabolism nor ascrobate-independent hydroxylation was altered by treatment with dbcAMP.", "contents": "Ascorbate-independent proline hydroxylation resulting from viral transformation of Balb 3T3 cells and unaffected by dibutyryl cAMP treatment. Collagen synthesis, hydroxylation of proline in collagen, and collagen secretion were studied in the contact-inhibited mouse fibroblast line, Balb 3T3; the Kirsten virus transformed line, Ki-3T3; and dibutyryl cAMP (dbcAMP)-treated Ki-3T3 cells, during the various phases of the growth cycle. Transformed cells in both logarithmic and stationary phase produced lower levels of collagen than the parent line but 85-90% of the theoretically possible hydroxyproline residues of the collagen were formed even when ascorbic acid was not added to the culture medium. Moreover, the transformed cells showed only about a 20% increase of collagen secretion upon addition of ascorbate. This was in contrast to the ascorbate requirement for maximal proline hydroxylation and the 2-3 fold stimulation of collagen secretion by ascorbate in the parent Balb 3T3 cells. Although dbcAMP treatment caused Ki-3T3 cells to assume a more normal morphology and increased the relative rate of collagen synthesis to levels similar to that of 3T3, such treatment did not restore an ascorbate requirement for proline hydroxylation or collagen secretion. The specific activity of the enzyme prolyl hydroxylase also was not affected by dbcAMP treatment although collagen synthesis was increased by such treatment. In addition, it was found that ascorbic acid was not effective in activating prolyl hydroxylase derived from Ki-3T3 or dbcAMP-treated Ki-3T3 cell cultures either in logarithmic phase or stationary phase. Ki-3T3 cultures did not accumulate ascorbic acid in cells or medium nor was ascorbic acid synthesized from the precursor 14C-glucuronate in cell homogenates. The results suggest that virally transformed Balb 3T3 cells acquire the capacity to synthesize a reducing cofactor for prolyl hydroxylase and that this function may be related to the increased glycolytic metabolism of these cells since neither cellular metabolism nor ascrobate-independent hydroxylation was altered by treatment with dbcAMP."}
{"id": "PMID:185227", "title": "Heterogeneity of phospholipid synthesis in rat liver endoplasmic reticulum during proliferation of smooth membranes.", "content": "During proliferation of smooth endoplasmic reticulum (SER) induced by phenobarbital the specific activity of acyltransferases of the smooth microsomes increases, there is a transient rise in the phospholipid/protein ratio of these membranes, and an increased incorporation of [14C]glycerol into smooth-membrane phospholipid. Microsomes separated into subfractions on 2 gradients exhibited a heterogeneous distribution of these characteristics, indicating a non-uniform distribution of the site of phospholipid synthesis in the ER under these conditions. Cytochemical localization of acyltransferases on whole liver and smooth and rough microsomes confirmed this heterogeneity, and indicated that the distribution of this activity was not restricted to any morphologically distinct site in the ER of the intact cell. After 4 days of phenobarbital treatment the increased membrane is restricted to lighter subfractions and is similar in distribution to that of increased acyltransferase activity. These results indicate that the synthesis of membrane phospholipid and the growth of the SER in response to phenobarbital is not uniform but occurs at randomly dispersed sites in the SER while proteins may be added preferentially at these sites resulting in a final uniform distribution.", "contents": "Heterogeneity of phospholipid synthesis in rat liver endoplasmic reticulum during proliferation of smooth membranes. During proliferation of smooth endoplasmic reticulum (SER) induced by phenobarbital the specific activity of acyltransferases of the smooth microsomes increases, there is a transient rise in the phospholipid/protein ratio of these membranes, and an increased incorporation of [14C]glycerol into smooth-membrane phospholipid. Microsomes separated into subfractions on 2 gradients exhibited a heterogeneous distribution of these characteristics, indicating a non-uniform distribution of the site of phospholipid synthesis in the ER under these conditions. Cytochemical localization of acyltransferases on whole liver and smooth and rough microsomes confirmed this heterogeneity, and indicated that the distribution of this activity was not restricted to any morphologically distinct site in the ER of the intact cell. After 4 days of phenobarbital treatment the increased membrane is restricted to lighter subfractions and is similar in distribution to that of increased acyltransferase activity. These results indicate that the synthesis of membrane phospholipid and the growth of the SER in response to phenobarbital is not uniform but occurs at randomly dispersed sites in the SER while proteins may be added preferentially at these sites resulting in a final uniform distribution."}
{"id": "PMID:185228", "title": "A theoretical study of the effects of cyclic AMP phosphodiesterases during aggregation in Dictyostelium.", "content": "During aggregation the larger Dictyostelium species use cAMP as a chemoattractant and possibly also as a transmitter. In passage from cell to cell, cAMP levels are modulated by diffusion and by enzyme hydrolysis. It appears that the important cAMP-hydrolysing enzyme is a phosphodiesterase bound to the cell membrane, the main roles of which are (1) very fast hydrolysis of cAMP and (2) steepening of spatial cAMP gradients. An extracellular phosphodiesterase has no function, so far as can be conjectured from present data.", "contents": "A theoretical study of the effects of cyclic AMP phosphodiesterases during aggregation in Dictyostelium. During aggregation the larger Dictyostelium species use cAMP as a chemoattractant and possibly also as a transmitter. In passage from cell to cell, cAMP levels are modulated by diffusion and by enzyme hydrolysis. It appears that the important cAMP-hydrolysing enzyme is a phosphodiesterase bound to the cell membrane, the main roles of which are (1) very fast hydrolysis of cAMP and (2) steepening of spatial cAMP gradients. An extracellular phosphodiesterase has no function, so far as can be conjectured from present data."}
{"id": "PMID:185229", "title": "Observation on intranuclear crystal and nucleolar size at different stages of cell differentiation in the midgut epithelium of several insects.", "content": "Based on an inverse size relationship between nuclear crystal and nucleolus in different cells it has been postulated by several authors that the crystal develops from nucleolar materials. The purpose of the present paper is to investigate the validity of this argument. Intranuclear proteinaceous crystals appear in differentiating midgut cells of Gyrinus marinus and Tenebrio molitor. In an autoradiographic study we have previously demonstrated in these two species that the crystals do not develop from nucleolar materials. However, an inverse relationship with regard to size is observed between these 2 structures during the cell differentiation: the cross-sectional area of the nucleolus decreases when the cross-sectional area of the crystal increases. But a decrease in size of the nucleolus is also observed during the differentiation of the midgut cells of Gyrinus natator where the crystals are not present. Consequently an inverse size relationship cannot be a sufficient argument to postulate that intranuclear crystals and nucleoli are interconvertible structures; decrease in size of the nucleolus is not related to development of the intranuclear crystal.", "contents": "Observation on intranuclear crystal and nucleolar size at different stages of cell differentiation in the midgut epithelium of several insects. Based on an inverse size relationship between nuclear crystal and nucleolus in different cells it has been postulated by several authors that the crystal develops from nucleolar materials. The purpose of the present paper is to investigate the validity of this argument. Intranuclear proteinaceous crystals appear in differentiating midgut cells of Gyrinus marinus and Tenebrio molitor. In an autoradiographic study we have previously demonstrated in these two species that the crystals do not develop from nucleolar materials. However, an inverse relationship with regard to size is observed between these 2 structures during the cell differentiation: the cross-sectional area of the nucleolus decreases when the cross-sectional area of the crystal increases. But a decrease in size of the nucleolus is also observed during the differentiation of the midgut cells of Gyrinus natator where the crystals are not present. Consequently an inverse size relationship cannot be a sufficient argument to postulate that intranuclear crystals and nucleoli are interconvertible structures; decrease in size of the nucleolus is not related to development of the intranuclear crystal."}
{"id": "PMID:185230", "title": "Determination of conjugated and esterified estrogens in pharmaceutical tablet dosage forms by high-pressure, normal-phase partition chromatography.", "content": "A high-pressure, normal-phase partition chromatographic method for the identification and determination of conjugated and esterified estrogens in pharmaceutical tablet dosage forms is described. The method is based on the separation of the estrogen sulfate esters on a conventional diatomaceous earth-H20 column, followed by HCI-methanol hydrolysis, and finally a chromatographic separation on a chemically bonded ether (ETH-Permaphase) column and measurement. Mobile phases found useful were combinations of 2-propanol and n-heptane. Equillin and -dehydroestrone, a structurally related isomer, not separately determined in the proposed method, are determined as a sum by performing a chromatographic study of their corresponding 2, 4-dinitrophenylhydrazine derivatives. Studies have indicated several estrogen derivatives can be rapidly formed and then separated on the same column, providing a useful qualitative analysis scheme. Commercial tablet dosage forms were analyzed for conjugated and esterified estrogens and the results are presented.", "contents": "Determination of conjugated and esterified estrogens in pharmaceutical tablet dosage forms by high-pressure, normal-phase partition chromatography. A high-pressure, normal-phase partition chromatographic method for the identification and determination of conjugated and esterified estrogens in pharmaceutical tablet dosage forms is described. The method is based on the separation of the estrogen sulfate esters on a conventional diatomaceous earth-H20 column, followed by HCI-methanol hydrolysis, and finally a chromatographic separation on a chemically bonded ether (ETH-Permaphase) column and measurement. Mobile phases found useful were combinations of 2-propanol and n-heptane. Equillin and -dehydroestrone, a structurally related isomer, not separately determined in the proposed method, are determined as a sum by performing a chromatographic study of their corresponding 2, 4-dinitrophenylhydrazine derivatives. Studies have indicated several estrogen derivatives can be rapidly formed and then separated on the same column, providing a useful qualitative analysis scheme. Commercial tablet dosage forms were analyzed for conjugated and esterified estrogens and the results are presented."}
{"id": "PMID:185231", "title": "Hypertensive virilizing adrenal hyperplasia with minimal impairment of synthetic route to cortisol.", "content": "One of the first described cases of hypertensive virilizing adrenal hyperplasia (VAH) (Pediatrics 8: 805, 1951) has been followed from age 2 1/2 until age 26. Blood pressure as an infant was 150/90, and at age 25 was 220/160. During childhood the patient was lost to follow-up for prolonged periods, and received no therapy from age 20 to 25. At this time 24 h urinary excretion of 17-ketosteroids was 89 mg; tetrahydro 11-deoxycortisol (tetrahydro S), 47 mg and pregnanetriol 5.7 mg. Hourly measurements of several plasma steroids utilizing sephadex LH 20 chromatography and competitive protein binding were made during 24 h; concentration ranges were made during 24 h; concentration ranges were as follows (mug/100 ml): 11-deoxycortisol 8-40; cortisol 0-48; corticosterone 0-15; deoxycorticosterone 1-18. Plasma cortisol, especially showed a significiant morning impairment, but reached normal and even markedly elevated levels during the day and early evening. Urinary cyclic AMP per 24 h ranged from 5.3 to 11.6 n mol/mg creatinine before therapy, and was 1.9 n mol after therapy. The results suggest either the formation of an alternate pathway to cortisol synthesis, or the existence of a form of VAH with two independent 11-B hydroxylating systems, exhibiting only minimal impairment of the synthetic route to cortisol. The latter would support the presence of two independent 11-B hydroxylating systems in the normal human adrenal. This has been suggested by Zachmann et al. (J Clin Endocrinol Metab 33: 501, 1971) to be true in infancy. Our observations on an adult indicate that these two systems may not be transitory, but persist into adulthood.", "contents": "Hypertensive virilizing adrenal hyperplasia with minimal impairment of synthetic route to cortisol. One of the first described cases of hypertensive virilizing adrenal hyperplasia (VAH) (Pediatrics 8: 805, 1951) has been followed from age 2 1/2 until age 26. Blood pressure as an infant was 150/90, and at age 25 was 220/160. During childhood the patient was lost to follow-up for prolonged periods, and received no therapy from age 20 to 25. At this time 24 h urinary excretion of 17-ketosteroids was 89 mg; tetrahydro 11-deoxycortisol (tetrahydro S), 47 mg and pregnanetriol 5.7 mg. Hourly measurements of several plasma steroids utilizing sephadex LH 20 chromatography and competitive protein binding were made during 24 h; concentration ranges were made during 24 h; concentration ranges were as follows (mug/100 ml): 11-deoxycortisol 8-40; cortisol 0-48; corticosterone 0-15; deoxycorticosterone 1-18. Plasma cortisol, especially showed a significiant morning impairment, but reached normal and even markedly elevated levels during the day and early evening. Urinary cyclic AMP per 24 h ranged from 5.3 to 11.6 n mol/mg creatinine before therapy, and was 1.9 n mol after therapy. The results suggest either the formation of an alternate pathway to cortisol synthesis, or the existence of a form of VAH with two independent 11-B hydroxylating systems, exhibiting only minimal impairment of the synthetic route to cortisol. The latter would support the presence of two independent 11-B hydroxylating systems in the normal human adrenal. This has been suggested by Zachmann et al. (J Clin Endocrinol Metab 33: 501, 1971) to be true in infancy. Our observations on an adult indicate that these two systems may not be transitory, but persist into adulthood."}
{"id": "PMID:185232", "title": "Radioimmunoassay of 18-hydroxy-11-deoxycorticosterone in plasma.", "content": "A method is described for the radioimmunoassay of 18-OH-DOC using antibodies generated in rabbits against the carboxymethoxime derivative coupled to bovine serum albumin. The procedure uses 4 ml of plasma with intra and interassay variations of 8 and 9% respectively. Standard 18-OH-DOC added to plasma from an adrenalectomized patient gave a regression equation, Y=0.974X+/-2.210 and a correlation coefficient of 0.999. The only cross reacting steroid, 18-OH-B which may lead to falsely high levels is removed by a single thin layer chromatographic step. Blood levels in normal subjects agree closely with those calculated indirectly by metabolic clearance and secretion rate measurements. ACTH stimulation produced an 18-fold increase in plasma concentration while dexamethasone suppression decreased levels 3-fold. Four hours in the upright position resulted in a decreased plasma concentration while aldosterone increased. No significant response to dietary sodium restriction could be demonstrated.", "contents": "Radioimmunoassay of 18-hydroxy-11-deoxycorticosterone in plasma. A method is described for the radioimmunoassay of 18-OH-DOC using antibodies generated in rabbits against the carboxymethoxime derivative coupled to bovine serum albumin. The procedure uses 4 ml of plasma with intra and interassay variations of 8 and 9% respectively. Standard 18-OH-DOC added to plasma from an adrenalectomized patient gave a regression equation, Y=0.974X+/-2.210 and a correlation coefficient of 0.999. The only cross reacting steroid, 18-OH-B which may lead to falsely high levels is removed by a single thin layer chromatographic step. Blood levels in normal subjects agree closely with those calculated indirectly by metabolic clearance and secretion rate measurements. ACTH stimulation produced an 18-fold increase in plasma concentration while dexamethasone suppression decreased levels 3-fold. Four hours in the upright position resulted in a decreased plasma concentration while aldosterone increased. No significant response to dietary sodium restriction could be demonstrated."}
{"id": "PMID:185233", "title": "Chemical characterization of ectopic ACTH purified from a malignant thymic carcinoid tumor.", "content": "ACTH was purified from thymic tumor associated with ectopic ACTH production by gel filtration and ion exchange chromatography. Amino acid composition and C- and N-terminal analyses indicated that this tumor ACTH was comprised of the 2-38 sequence of authentic pituitary ACTH. The observations suggest that the mode of cleavage of this tumor ACTH from its precursor is different from that of pituitary ACTH.", "contents": "Chemical characterization of ectopic ACTH purified from a malignant thymic carcinoid tumor. ACTH was purified from thymic tumor associated with ectopic ACTH production by gel filtration and ion exchange chromatography. Amino acid composition and C- and N-terminal analyses indicated that this tumor ACTH was comprised of the 2-38 sequence of authentic pituitary ACTH. The observations suggest that the mode of cleavage of this tumor ACTH from its precursor is different from that of pituitary ACTH."}
{"id": "PMID:185234", "title": "Periodic remission in Cushing's disease with paradoxical dexamethasone response: an expression of periodic hormonogenesis.", "content": "A patient with Cushing's disease due to a chromophobe adenoma was studied for 243 days before pituitary surgery and evidence for periodicity in cortisol steroid production was found with cycles occurring every 85.8 days (peak-to-peak length), associated with laboratory remissions and paradoxical response to dexamethasone. The autonomy of ACTH secretion was suggested by the nonresponsiveness to repeated lysine-vasopressin stimulation tests and lack of increase in urinary 170HCS following metyrapone. A distinct response of the hyperplastic glands (as demonstrated by percutaneous adrenal venography) was obtained on several B1-24 corticotropin stimulation. The patient's hypercortisolism disappeared following removal of the chromophobe adenoma through transphenoidal hypophysectomy.", "contents": "Periodic remission in Cushing's disease with paradoxical dexamethasone response: an expression of periodic hormonogenesis. A patient with Cushing's disease due to a chromophobe adenoma was studied for 243 days before pituitary surgery and evidence for periodicity in cortisol steroid production was found with cycles occurring every 85.8 days (peak-to-peak length), associated with laboratory remissions and paradoxical response to dexamethasone. The autonomy of ACTH secretion was suggested by the nonresponsiveness to repeated lysine-vasopressin stimulation tests and lack of increase in urinary 170HCS following metyrapone. A distinct response of the hyperplastic glands (as demonstrated by percutaneous adrenal venography) was obtained on several B1-24 corticotropin stimulation. The patient's hypercortisolism disappeared following removal of the chromophobe adenoma through transphenoidal hypophysectomy."}
{"id": "PMID:185235", "title": "Gonadotropin output in congenital adrenal hyperplasia before and after adrenal suppression.", "content": "Basal release of gonadotropin and the response to an infusion of 100 mug of synthetic luteinizing hormone releasing hormone (LRH) were studied in a teenage girl with congenital adrenal hyperplasia (CAH). The initial study was done during a period of poor adrenal suppression, and second study was done after adequate adrenal suppression was achieved. To assess adrenal function, circulating levels of adrenal steroid hormones were evaluated continuously over a 24 h period. During the period increased production of adrenal androgens, the pattern of gonadotropin release was that of a prepubertal child. After 3 months of adrenal suppression the pattern of gonadotropin secretion was similar to that of a normal girl in mid-puberty. This demonstrates the rapid change from prepubertal to pubertal gonadotropin dynamics in a teenage patient following adequate suppression of androgens from the adrenal.", "contents": "Gonadotropin output in congenital adrenal hyperplasia before and after adrenal suppression. Basal release of gonadotropin and the response to an infusion of 100 mug of synthetic luteinizing hormone releasing hormone (LRH) were studied in a teenage girl with congenital adrenal hyperplasia (CAH). The initial study was done during a period of poor adrenal suppression, and second study was done after adequate adrenal suppression was achieved. To assess adrenal function, circulating levels of adrenal steroid hormones were evaluated continuously over a 24 h period. During the period increased production of adrenal androgens, the pattern of gonadotropin release was that of a prepubertal child. After 3 months of adrenal suppression the pattern of gonadotropin secretion was similar to that of a normal girl in mid-puberty. This demonstrates the rapid change from prepubertal to pubertal gonadotropin dynamics in a teenage patient following adequate suppression of androgens from the adrenal."}
{"id": "PMID:185236", "title": "Evaluation of the sodium polyanethol sulfonate disk test for the identification of Peptostreptococcus anaerobius.", "content": "The previously reported sodium polyanethol sulfonate disk test for the identification of Peptostreptococcus anaerobius (Graves et al., 1974) was evaluated, with modifications. Three bands of brucella agar, three inoculum sizes, and two inoculum sources were compared. Nine stock cultures of P. anaerobius (eight normal flora isolates and ATCC 27337) and 16 fresh clinical isolates were used. All cultures of P. anaerobius showed inhibition zones of 12 to 30 mm in diameter, regardless of test conditions. Out of 103 clinical isolates of other species of anaerobic gram-positive cocci tested, only two had an inhibition zone size in this range (one P. micros of 11 studied had a zone of 12 mm and one P. prevotii of 14 studied had a zone of 16). The test had an overall accuracy of 98% in the identification of P. anaerobius from clinical specimens. Since P. anaerobius accounts for one-fifth to one-third of all anaerobic gram-positive cocci encountered in clinical specimens, this simple and rapid technique can be very useful for presumptive identification.", "contents": "Evaluation of the sodium polyanethol sulfonate disk test for the identification of Peptostreptococcus anaerobius. The previously reported sodium polyanethol sulfonate disk test for the identification of Peptostreptococcus anaerobius (Graves et al., 1974) was evaluated, with modifications. Three bands of brucella agar, three inoculum sizes, and two inoculum sources were compared. Nine stock cultures of P. anaerobius (eight normal flora isolates and ATCC 27337) and 16 fresh clinical isolates were used. All cultures of P. anaerobius showed inhibition zones of 12 to 30 mm in diameter, regardless of test conditions. Out of 103 clinical isolates of other species of anaerobic gram-positive cocci tested, only two had an inhibition zone size in this range (one P. micros of 11 studied had a zone of 12 mm and one P. prevotii of 14 studied had a zone of 16). The test had an overall accuracy of 98% in the identification of P. anaerobius from clinical specimens. Since P. anaerobius accounts for one-fifth to one-third of all anaerobic gram-positive cocci encountered in clinical specimens, this simple and rapid technique can be very useful for presumptive identification."}
{"id": "PMID:185237", "title": "Screening tests for hepatitis B antigen and antibody in two colleges of education and studies on the relationship between nonspecific positive antibody tests and EB virus infection.", "content": "Sera from 627 students entering Colleges of Education between 1969 and 1972 were tested for hepatitis B surface antigen and antibody. One was found positive for antigen, none for antibody. Six for 15 positive Hepanosticon results and two positive Hepatest results occurred in sera which also gave positive heterophil antibody tests indicative of current or recent EB virus infection. One of these six sera was still positive in the Hepanosticon test after one absorption, and one of two Hepatests gave no positive reaction with the control cells. Eleven of 14 sera from cases of infectious mononucleosis gave positive Hepanosticon results and two were still positive after one absorption. Seven were positive in the Hepatest and only three of these were positive with the control cells. The control tests in the Hepanosticon and Hepatest do not clearly identify all false positives due to Paul Bunnell antibody. It is suggested that when a positive result in a passive haemagglutination test can be removed by absorption or if positive after absorption cannot be confirmed by other tests for hepatitis Bs antigen, the patient from whom the serum specimen was taken should be investigated for indications of current EB virus infection.", "contents": "Screening tests for hepatitis B antigen and antibody in two colleges of education and studies on the relationship between nonspecific positive antibody tests and EB virus infection. Sera from 627 students entering Colleges of Education between 1969 and 1972 were tested for hepatitis B surface antigen and antibody. One was found positive for antigen, none for antibody. Six for 15 positive Hepanosticon results and two positive Hepatest results occurred in sera which also gave positive heterophil antibody tests indicative of current or recent EB virus infection. One of these six sera was still positive in the Hepanosticon test after one absorption, and one of two Hepatests gave no positive reaction with the control cells. Eleven of 14 sera from cases of infectious mononucleosis gave positive Hepanosticon results and two were still positive after one absorption. Seven were positive in the Hepatest and only three of these were positive with the control cells. The control tests in the Hepanosticon and Hepatest do not clearly identify all false positives due to Paul Bunnell antibody. It is suggested that when a positive result in a passive haemagglutination test can be removed by absorption or if positive after absorption cannot be confirmed by other tests for hepatitis Bs antigen, the patient from whom the serum specimen was taken should be investigated for indications of current EB virus infection."}
{"id": "PMID:185238", "title": "Malignant fibrous histiocytoma with diffuse spinal nerve involvement.", "content": "Two cases of malignant fibrous histiocytoma in which paraplegia was a major feature are presented. The histological features of the tumours are discussed with particular emphasis on the neural involvement. A brief review of the literature on the subject is included.", "contents": "Malignant fibrous histiocytoma with diffuse spinal nerve involvement. Two cases of malignant fibrous histiocytoma in which paraplegia was a major feature are presented. The histological features of the tumours are discussed with particular emphasis on the neural involvement. A brief review of the literature on the subject is included."}
{"id": "PMID:185239", "title": "Hepatic lesions in patients treated with synthetic anabolic steriods.", "content": "Hepatic abnormalities are described in three patients who received synthetic anabolic steroids. A child with Franconi's anaemia was treated for four years and at necropsy the liver showed generalized hyperplasia, hyperplastic nodules, and a benign hepatoma. Two adults received only three months' therapy with synthetic androgens; in one there was generalized hepatic hyperplasia and in the other widespread nodular hyperplasia. It is suggested that anabolic steroids may induce tumours through intermediate hyperplastic lesions, a sequence similar to that seen during tumour induction by carcinogens in experimental animals.", "contents": "Hepatic lesions in patients treated with synthetic anabolic steriods. Hepatic abnormalities are described in three patients who received synthetic anabolic steroids. A child with Franconi's anaemia was treated for four years and at necropsy the liver showed generalized hyperplasia, hyperplastic nodules, and a benign hepatoma. Two adults received only three months' therapy with synthetic androgens; in one there was generalized hepatic hyperplasia and in the other widespread nodular hyperplasia. It is suggested that anabolic steroids may induce tumours through intermediate hyperplastic lesions, a sequence similar to that seen during tumour induction by carcinogens in experimental animals."}
{"id": "PMID:185240", "title": "Chemotherapeutic compounds and Acanthamoebae from eye infections.", "content": "The amoebicidal and amoebistatic action in vitro of 24 compounds was tested on two strains of Acanthamoeba, A. polyphaga and A. castellanii, isolated from eye infections in this country. For comparison, the Ryan strain of A. castellanii and Naegleria gruberi L-1 were also examined. Nine compounds showed sufficient activity to merit further consideration, ie, acriflavine, proflavine, hydroxystilbamidine isethionate, paromomycin, miconazole, amphoterin, neomycin, polymyxin, and the last two combined in Neosporin.", "contents": "Chemotherapeutic compounds and Acanthamoebae from eye infections. The amoebicidal and amoebistatic action in vitro of 24 compounds was tested on two strains of Acanthamoeba, A. polyphaga and A. castellanii, isolated from eye infections in this country. For comparison, the Ryan strain of A. castellanii and Naegleria gruberi L-1 were also examined. Nine compounds showed sufficient activity to merit further consideration, ie, acriflavine, proflavine, hydroxystilbamidine isethionate, paromomycin, miconazole, amphoterin, neomycin, polymyxin, and the last two combined in Neosporin."}
{"id": "PMID:185241", "title": "Measurement of heterophil antibody and antibodies to EB viral capsid antigen IgG and IgM in suspected cases of infectious mononucleosis.", "content": "The EBV IgG titres in acute and convalescent specimens from 97 cases of infectious mononucleosis were compared with titres from acute and convalescent sera from 96 students with illnesses resembling infectious mononucleosis but without heterophil antibody, EB IgM or EB IgG seroconversion; and also with titres from 91 healthy students known to have had EB IgG antibody for at least six months. These titres were related to the titre of the Research Standard A.66/235 for infectious mononucleosis serum prepared by the National Institute for Biological Standards and Control. Serial sera were tested for heterophil antibody and EBVCA specific IgG and IgM from 61 university students with infectious mononucleosis. The period of persistence of heterophil antibody and EBV IgM after illness was outlined from the results of the tests. Single sera from 406 patients in hospital or general practice sent to the diagnostic laboratory for heterophil antibody tests were also tested for EBV antibodies without prior knowledge of the heterophil antibody result. The close agreement between heterophil antibody and EBV IgM results is shown. False positive EB IgM results were correlated with the presence of rheumatoid factor.", "contents": "Measurement of heterophil antibody and antibodies to EB viral capsid antigen IgG and IgM in suspected cases of infectious mononucleosis. The EBV IgG titres in acute and convalescent specimens from 97 cases of infectious mononucleosis were compared with titres from acute and convalescent sera from 96 students with illnesses resembling infectious mononucleosis but without heterophil antibody, EB IgM or EB IgG seroconversion; and also with titres from 91 healthy students known to have had EB IgG antibody for at least six months. These titres were related to the titre of the Research Standard A.66/235 for infectious mononucleosis serum prepared by the National Institute for Biological Standards and Control. Serial sera were tested for heterophil antibody and EBVCA specific IgG and IgM from 61 university students with infectious mononucleosis. The period of persistence of heterophil antibody and EBV IgM after illness was outlined from the results of the tests. Single sera from 406 patients in hospital or general practice sent to the diagnostic laboratory for heterophil antibody tests were also tested for EBV antibodies without prior knowledge of the heterophil antibody result. The close agreement between heterophil antibody and EBV IgM results is shown. False positive EB IgM results were correlated with the presence of rheumatoid factor."}
{"id": "PMID:185242", "title": "Cell-mediated immunity to herpes simplex virus in man. V. Antibody-mediated cell-dependent immune lysis of herpes virus-infected target cells.", "content": "Thirty-four patients, subject to recurrent herpes labialis, have been studied. They have all been shown to have high serum levels of an antibody to HSV1. This antibody has the property of sensitizing HSV1-infected target cells to lysis by nonimmune effector lymphocytes. Of 23 subjects who gave no history of herpes labialis, only four had antibody demonstrable by this technique. The level of antibody remains essentially unchanged despite recrudescenes of herpes labialis in the susceptible subjects. Effector cell activity was present in all of these and other subjects tested except for two who were suffering from chronic lymphatic leukemia. We have positive evidence that the effector cells in this system are neither T cells nor macrophages. Additional evidence suggests that the effector cells may be \"null\" cells.", "contents": "Cell-mediated immunity to herpes simplex virus in man. V. Antibody-mediated cell-dependent immune lysis of herpes virus-infected target cells. Thirty-four patients, subject to recurrent herpes labialis, have been studied. They have all been shown to have high serum levels of an antibody to HSV1. This antibody has the property of sensitizing HSV1-infected target cells to lysis by nonimmune effector lymphocytes. Of 23 subjects who gave no history of herpes labialis, only four had antibody demonstrable by this technique. The level of antibody remains essentially unchanged despite recrudescenes of herpes labialis in the susceptible subjects. Effector cell activity was present in all of these and other subjects tested except for two who were suffering from chronic lymphatic leukemia. We have positive evidence that the effector cells in this system are neither T cells nor macrophages. Additional evidence suggests that the effector cells may be \"null\" cells."}
{"id": "PMID:185243", "title": "Decreased adrenergic responses in lymphocytes and granulocytes in atopic eczema.", "content": "The physiologic and cyclic adenosine monophosphate (cAMP) response to beta adrenergic stimulation in lymphocytes and granulocytes was examined in atopic eczema. These cells were isolated by Ficoll-Hypaque gradient from 10 patients with atopic eczema, and their responses were compared to 10 normal subjects. In eczema, basal concentrations of cAMP were normal in both lymphocytes and granulocytes. Lymphocyte cAMP response in eczema was decreased both to epinephrine (10-5 M) and to isoproterenol (10-5 M) but normal to prostaglandin E1 (PGE1). It was also noted that the glycogenolysis response to isoproterenol was significantly less at 10-5 M in eczema, but the fall in glycogen was normal with PGE (10-5 M and 10-7 M). The inhibition of lysosomal enzyme release from granulocytes after zymosan stimulation was significantly less (p less than 0.01) in eczema with all concentrations of isoproterenol tested. There was also a decrease in cyclic AMP response to isoproterenol in the polymorphonuclear leukocytes. PGE1 inhibited lysosomal enzyme release and stimulated cAMP normally. In eczema, both lymphocytes and polymorphonuclear leukocytes have a decreased beta adrenergic response.", "contents": "Decreased adrenergic responses in lymphocytes and granulocytes in atopic eczema. The physiologic and cyclic adenosine monophosphate (cAMP) response to beta adrenergic stimulation in lymphocytes and granulocytes was examined in atopic eczema. These cells were isolated by Ficoll-Hypaque gradient from 10 patients with atopic eczema, and their responses were compared to 10 normal subjects. In eczema, basal concentrations of cAMP were normal in both lymphocytes and granulocytes. Lymphocyte cAMP response in eczema was decreased both to epinephrine (10-5 M) and to isoproterenol (10-5 M) but normal to prostaglandin E1 (PGE1). It was also noted that the glycogenolysis response to isoproterenol was significantly less at 10-5 M in eczema, but the fall in glycogen was normal with PGE (10-5 M and 10-7 M). The inhibition of lysosomal enzyme release from granulocytes after zymosan stimulation was significantly less (p less than 0.01) in eczema with all concentrations of isoproterenol tested. There was also a decrease in cyclic AMP response to isoproterenol in the polymorphonuclear leukocytes. PGE1 inhibited lysosomal enzyme release and stimulated cAMP normally. In eczema, both lymphocytes and polymorphonuclear leukocytes have a decreased beta adrenergic response."}
{"id": "PMID:185284", "title": "Effect of heat on foot-and-mouth disease virus (FMDV) in the components of milk from FMDV-infected cows.", "content": "Foot-and-mouth disease virus (FMDV) survived in skim milk, cream and the pelleted cellular debris components of milk obtained from FMDV-infected cows after pasteurization at 72 degrees C for 0-25 min. Virus was recovered from whole milk of infected cows after that milk was heated at 72 degrees C. for 5 min. and from the skim milk component after it was heated at the same temperature for 2 min. Evaporation of the whole milk samples after they were heated at 72 degrees C. for 3 min. did not inactivate the virus, but evaporation of infected skim milk samples after they were heated at 72 degrees C. for 0-5 min. did inactivate the virus. FMDV survived in the cream component after it was heated at 93 degrees C. for 0-25 min.", "contents": "Effect of heat on foot-and-mouth disease virus (FMDV) in the components of milk from FMDV-infected cows. Foot-and-mouth disease virus (FMDV) survived in skim milk, cream and the pelleted cellular debris components of milk obtained from FMDV-infected cows after pasteurization at 72 degrees C for 0-25 min. Virus was recovered from whole milk of infected cows after that milk was heated at 72 degrees C. for 5 min. and from the skim milk component after it was heated at the same temperature for 2 min. Evaporation of the whole milk samples after they were heated at 72 degrees C. for 3 min. did not inactivate the virus, but evaporation of infected skim milk samples after they were heated at 72 degrees C. for 0-5 min. did inactivate the virus. FMDV survived in the cream component after it was heated at 93 degrees C. for 0-25 min."}
{"id": "PMID:185285", "title": "Prevalent serotypes of Bordetella pertussis in non-vaccinated communities.", "content": "In many countries, the prevalent serotypes of Bordetella pertussis have changed from a mixture of types 1,2,3 and 1,2 (organisms possessing antigen 2) to a predominance of type 1,3. The timing of the change in different countries is shown to be related to the introduction of mass-vaccination with material rich in antigens 1 and 2 but weak in, or devoid of, antigen 3. In several parts of the world, there have been outbreaks of type 1,3 infection in fully vaccinated children. Non-vaccinated communities in various parts of the world still show the pattern of serotypes which existed elsewhere before mass-vaccination. In order to avoid the disappointments experienced in the past, it is essential that pertussis vaccine for use in previously non-vaccinated communities, like that for any other country, should be rich in each of the three antigens.", "contents": "Prevalent serotypes of Bordetella pertussis in non-vaccinated communities. In many countries, the prevalent serotypes of Bordetella pertussis have changed from a mixture of types 1,2,3 and 1,2 (organisms possessing antigen 2) to a predominance of type 1,3. The timing of the change in different countries is shown to be related to the introduction of mass-vaccination with material rich in antigens 1 and 2 but weak in, or devoid of, antigen 3. In several parts of the world, there have been outbreaks of type 1,3 infection in fully vaccinated children. Non-vaccinated communities in various parts of the world still show the pattern of serotypes which existed elsewhere before mass-vaccination. In order to avoid the disappointments experienced in the past, it is essential that pertussis vaccine for use in previously non-vaccinated communities, like that for any other country, should be rich in each of the three antigens."}
{"id": "PMID:185286", "title": "The skin flora of the hemiplegic hand.", "content": "More organisms were found on the paralysed hands of hemiplegic patients than on their unaffected ones. However, both showed considerably higher bacterial counts than did geriatric patients without paralysis. An infection rate for Cl. welchi of 15% was found in the paralysed hands.", "contents": "The skin flora of the hemiplegic hand. More organisms were found on the paralysed hands of hemiplegic patients than on their unaffected ones. However, both showed considerably higher bacterial counts than did geriatric patients without paralysis. An infection rate for Cl. welchi of 15% was found in the paralysed hands."}
{"id": "PMID:185287", "title": "Age-specific incidence of neutralization antibodies of Herpes simplex virus.", "content": "Sera of 1255 individuals from Novi Sad, varying in age from less than 1 month to 69 years, have been tested for neutralization antibodies to Herpes implex virus type 1. The eight newborns tested and 97% of the 507 adults were positive, with titres ranging from 1/4 to 1/256. The titres in newborns were significantly lower than the titres in adults. After birth the maternal antibodies declined rapidly and 94% of infants at the age of greater than 6 months and less than 2 years were negative. After the first year infants in Novi Sad start to acquire herpes-neutralizing antibodies actively, reaching a 50% incidence of positives between the 2nd and 3rd year of age. Age-specific incidence rates of herpes positives found in Novi Sad have been compared with those reported from Edinburgh, Freiburg i. Br. and Louisiana. Possible influences of several circumstances upon the incidence rate of positives detected by the neutralization test are discussed.", "contents": "Age-specific incidence of neutralization antibodies of Herpes simplex virus. Sera of 1255 individuals from Novi Sad, varying in age from less than 1 month to 69 years, have been tested for neutralization antibodies to Herpes implex virus type 1. The eight newborns tested and 97% of the 507 adults were positive, with titres ranging from 1/4 to 1/256. The titres in newborns were significantly lower than the titres in adults. After birth the maternal antibodies declined rapidly and 94% of infants at the age of greater than 6 months and less than 2 years were negative. After the first year infants in Novi Sad start to acquire herpes-neutralizing antibodies actively, reaching a 50% incidence of positives between the 2nd and 3rd year of age. Age-specific incidence rates of herpes positives found in Novi Sad have been compared with those reported from Edinburgh, Freiburg i. Br. and Louisiana. Possible influences of several circumstances upon the incidence rate of positives detected by the neutralization test are discussed."}
{"id": "PMID:185288", "title": "Pathogenesis of foot-and-mouth disease: the lung as an additional portal of entry of the virus.", "content": "Donor cattle infected with foot and mouth disease (FMD) virus subtype O1 were used to expose experimental cattle. The pharyngeal virus growth and viraemia patterns after contact exposure were quite different from those obtained after intranasal inoculation and suggested that the lower respiratory tract might provide an additional portal of entry for the virus. A tracheotomy was performed on experimental cattle to let the respiration bypass the pharynx, followed by exposure to FMD virus by different routes. The results confirmed that FMD virus can enter the bloodstream via the lung, followed by haematogenic infection of the pharynx and other replication sites simultaneously. These observations led to further experiments in which the intravenous route of infection was used to study the interaction of virus growth in the phayrnx, in other sites, and in viraemia.", "contents": "Pathogenesis of foot-and-mouth disease: the lung as an additional portal of entry of the virus. Donor cattle infected with foot and mouth disease (FMD) virus subtype O1 were used to expose experimental cattle. The pharyngeal virus growth and viraemia patterns after contact exposure were quite different from those obtained after intranasal inoculation and suggested that the lower respiratory tract might provide an additional portal of entry for the virus. A tracheotomy was performed on experimental cattle to let the respiration bypass the pharynx, followed by exposure to FMD virus by different routes. The results confirmed that FMD virus can enter the bloodstream via the lung, followed by haematogenic infection of the pharynx and other replication sites simultaneously. These observations led to further experiments in which the intravenous route of infection was used to study the interaction of virus growth in the phayrnx, in other sites, and in viraemia."}
{"id": "PMID:185289", "title": "Pathogenesis of foot-and-mouth disease: clearance of the virus from the circulation of cattle and goats during experimental viraemia.", "content": "Viraemia is an important aspect of the pathogenesis of infectious diseases, but the mechanisms of entry and removal of virus from the vascular system particularly in natural hosts are poorly understood. The results of this study showed that the clearance of foot and mouth disease virus (FMDV) from the circulation of cattle and goats followed the general rules for the clearance of inert particulate materials and other viruses from the circulation. High doses of infused FMDV were cleared less efficiently than low doses, probably as a result of a depletion of the reticulo-endothelial system by the higher doses. FMDV was cleared from the circulation of cattle at a considerably slower rate than from the circulation of goats, but in both species significant individual variation in clearance was observed. These results could explain individual as well as species variations relative to the onset and duration of viraemia.", "contents": "Pathogenesis of foot-and-mouth disease: clearance of the virus from the circulation of cattle and goats during experimental viraemia. Viraemia is an important aspect of the pathogenesis of infectious diseases, but the mechanisms of entry and removal of virus from the vascular system particularly in natural hosts are poorly understood. The results of this study showed that the clearance of foot and mouth disease virus (FMDV) from the circulation of cattle and goats followed the general rules for the clearance of inert particulate materials and other viruses from the circulation. High doses of infused FMDV were cleared less efficiently than low doses, probably as a result of a depletion of the reticulo-endothelial system by the higher doses. FMDV was cleared from the circulation of cattle at a considerably slower rate than from the circulation of goats, but in both species significant individual variation in clearance was observed. These results could explain individual as well as species variations relative to the onset and duration of viraemia."}
{"id": "PMID:185290", "title": "The assessment in sheep of an inactivated vaccine of parainfluenza 3 virus incorporating double stranded RNA (BRL 5907) as adjuvant.", "content": "The serological responses of conventionally reared sheep were compared after vaccination with inactivated parainfluenza 3 (PI3) virus incorporated in three different adjuvants. Inactivated PI3 virus with the double-stranded RNA, BRL 5907 in an oil emulsion was shown to stimulate higher serum antibody titres over the first 5 weeks after vaccination than virus with and without BCG emulsified in oil. The ability of this vaccine to protect specific pathogen-free lambs against challenge with PI3 virus was examined in a second experiment. In this experiment the vaccine stimulated virus neutralizing and haemagglutination inhibiting antibodies in the serum. After intranasal and intratracheal inoculation with PI3 virus at challenge, vaccinated lambs showed no clinical illness and virus isolation was confined, except in one lamb, to the first two days. In contrast, unvaccinated lambs developed respiratory disease and virus was isolated daily for 7 days after challenge.", "contents": "The assessment in sheep of an inactivated vaccine of parainfluenza 3 virus incorporating double stranded RNA (BRL 5907) as adjuvant. The serological responses of conventionally reared sheep were compared after vaccination with inactivated parainfluenza 3 (PI3) virus incorporated in three different adjuvants. Inactivated PI3 virus with the double-stranded RNA, BRL 5907 in an oil emulsion was shown to stimulate higher serum antibody titres over the first 5 weeks after vaccination than virus with and without BCG emulsified in oil. The ability of this vaccine to protect specific pathogen-free lambs against challenge with PI3 virus was examined in a second experiment. In this experiment the vaccine stimulated virus neutralizing and haemagglutination inhibiting antibodies in the serum. After intranasal and intratracheal inoculation with PI3 virus at challenge, vaccinated lambs showed no clinical illness and virus isolation was confined, except in one lamb, to the first two days. In contrast, unvaccinated lambs developed respiratory disease and virus was isolated daily for 7 days after challenge."}
{"id": "PMID:185291", "title": "Natural infection with influenza A (H3N2). The development, persistance and effect of antibodies to the surface antigens.", "content": "A technique for estimating antibodies to the neuraminidase antigens of influenza A is described. The antibody response to the haemagglutinin and neuraminidase antigens of influenza A (H3N2) was studied in a boys' public school over the four-year period 1970--4. During this time there were two outbreaks of influenza A and the effect of antibody on the result of natural challenge was investigated. No boy who had homotypic neuraminidase antibody had clinical influenza.", "contents": "Natural infection with influenza A (H3N2). The development, persistance and effect of antibodies to the surface antigens. A technique for estimating antibodies to the neuraminidase antigens of influenza A is described. The antibody response to the haemagglutinin and neuraminidase antigens of influenza A (H3N2) was studied in a boys' public school over the four-year period 1970--4. During this time there were two outbreaks of influenza A and the effect of antibody on the result of natural challenge was investigated. No boy who had homotypic neuraminidase antibody had clinical influenza."}
{"id": "PMID:185292", "title": "Cytomegalovirus excretion in gnotobiotic pigs.", "content": "Germ-free piglets were infected intranasally with porcine cytomegalovirus (PCMV) at 1 day (group A) or 3 weeks of age (group B). Viraemia and virus excretion by the nasal, pharyngeal and conjunctival routes was studied up to the time of death or to 12 weeks. Virus was also sought in tissues at death or at slaughter, as well as in a few urine samples. Viraemia was detected in group A between days 5 and 19 after infection and in group B between days 14 and 16 inclusive. The chief route of virus excretion was the nasal mucosa, followed by the pharynx and conjunctiva; the maximal duration of excretion by these routes was 32, 25 and 14 days for pigs of group A and 9, 7 and 4 days for group B. The quantity of virus was also greater in the former group, of which died of generalized PCMV infection. A viruria was demonstrated in 2 animals. Antibody detectable in indirect immunofluorescence (IIF) tests appeared towards the end of the third week, reaching maximal titres at 5 to 7 weeks after infection. The mean peak titre of antibody in group B was lower than in group A. Corticosteroid treatment at days 56--62 after infection resulted in some recrudescence of virus excretion, accompanied in group B by about a twofold increase in IIF antibody. PCMV was isolated in cultures of lung macrophages from 4 of 7 animals killed at about 12 weeks after inoculation.", "contents": "Cytomegalovirus excretion in gnotobiotic pigs. Germ-free piglets were infected intranasally with porcine cytomegalovirus (PCMV) at 1 day (group A) or 3 weeks of age (group B). Viraemia and virus excretion by the nasal, pharyngeal and conjunctival routes was studied up to the time of death or to 12 weeks. Virus was also sought in tissues at death or at slaughter, as well as in a few urine samples. Viraemia was detected in group A between days 5 and 19 after infection and in group B between days 14 and 16 inclusive. The chief route of virus excretion was the nasal mucosa, followed by the pharynx and conjunctiva; the maximal duration of excretion by these routes was 32, 25 and 14 days for pigs of group A and 9, 7 and 4 days for group B. The quantity of virus was also greater in the former group, of which died of generalized PCMV infection. A viruria was demonstrated in 2 animals. Antibody detectable in indirect immunofluorescence (IIF) tests appeared towards the end of the third week, reaching maximal titres at 5 to 7 weeks after infection. The mean peak titre of antibody in group B was lower than in group A. Corticosteroid treatment at days 56--62 after infection resulted in some recrudescence of virus excretion, accompanied in group B by about a twofold increase in IIF antibody. PCMV was isolated in cultures of lung macrophages from 4 of 7 animals killed at about 12 weeks after inoculation."}
{"id": "PMID:185293", "title": "Hypergammaglobulinemia in chickens congenitally infected with an avian leukosis virus.", "content": "Significantly elevated (2- to 5-fold higher than controls) serum levels of IgG were found in chickens congenitally infected with F42 strain of avian leukosis (ALV-F42) a subgroup A avian leukosis virus (ALV). A further increase in IgG levels in congenitally infected birds was found to be induced by injection of influenza virus in complete Freund's adjuvant(CFA). Serum immunoglobulin M (IgM) levels were not significantly elevated in ALV congenitally infected chickens except in those animals that had been injected with influenza virus in CFA. Hypergammaglobulinemia in ALV infected birds resulted only after congenital infection and not after infection of immunologically competent birds. Therefore this phenomenon appeared to have striking parallels with other persistent or chronic viral infections that have been previously described in mammals.", "contents": "Hypergammaglobulinemia in chickens congenitally infected with an avian leukosis virus. Significantly elevated (2- to 5-fold higher than controls) serum levels of IgG were found in chickens congenitally infected with F42 strain of avian leukosis (ALV-F42) a subgroup A avian leukosis virus (ALV). A further increase in IgG levels in congenitally infected birds was found to be induced by injection of influenza virus in complete Freund's adjuvant(CFA). Serum immunoglobulin M (IgM) levels were not significantly elevated in ALV congenitally infected chickens except in those animals that had been injected with influenza virus in CFA. Hypergammaglobulinemia in ALV infected birds resulted only after congenital infection and not after infection of immunologically competent birds. Therefore this phenomenon appeared to have striking parallels with other persistent or chronic viral infections that have been previously described in mammals."}
{"id": "PMID:185294", "title": "Depression of macrophage function by a factor produced by neoplasms: a merchanism for abrogation of immune surveillance.", "content": "The possibility that macrophages mediate surveillance against the development of neoplasms has been reciving increasing support. The acquisition, by neoplastic cells, of the capacity to subvert macrophage function may be an important mechanism by which they escape destruction by the host and become established tumors. Indeed, animals implanted with syngeneic neoplasms developed depressed macrophage migratory ability in vivo and chemotactic responsiveness in virto. It therefore seemed plausible that neoplasms might be capable of producing inhibitors of macrophage function. The present report describes the identification of such a low molecular weight (6,000 to 10,000), heat-stable inhibitor of murine macrophage accumulation in vivo and chemotaxis in vitro. The inhibitor of macrophages was present in four different murine neoplasms, but not present in normal liver, spleen, or inflammatory exudate cells and did not affect PMN chemotaxis in vitro. When given with low numbers of neoplastic cells, the inhibitor increased both the frequency of tumor development and rate of tumor growth. By producing inhibitors of macrophage function, neoplasms may escape initial host surveillance mechanisms.", "contents": "Depression of macrophage function by a factor produced by neoplasms: a merchanism for abrogation of immune surveillance. The possibility that macrophages mediate surveillance against the development of neoplasms has been reciving increasing support. The acquisition, by neoplastic cells, of the capacity to subvert macrophage function may be an important mechanism by which they escape destruction by the host and become established tumors. Indeed, animals implanted with syngeneic neoplasms developed depressed macrophage migratory ability in vivo and chemotactic responsiveness in virto. It therefore seemed plausible that neoplasms might be capable of producing inhibitors of macrophage function. The present report describes the identification of such a low molecular weight (6,000 to 10,000), heat-stable inhibitor of murine macrophage accumulation in vivo and chemotaxis in vitro. The inhibitor of macrophages was present in four different murine neoplasms, but not present in normal liver, spleen, or inflammatory exudate cells and did not affect PMN chemotaxis in vitro. When given with low numbers of neoplastic cells, the inhibitor increased both the frequency of tumor development and rate of tumor growth. By producing inhibitors of macrophage function, neoplasms may escape initial host surveillance mechanisms."}
{"id": "PMID:185295", "title": "Characterization of Ia8 antigen, thy-1.2 antigen, complement receptors, and virus production in a group of murine virus-induced leukemia cell lines.", "content": "Ia8, a cell membrane antigen controlled by gene(s) located in the I region of the H-2 complex, was found on 9 of 26 murine leukemia cell lines. Iaddition, 3 of the 9 Ia8-bearing lines had a membrane receptor for antigen-antibody-complement complexes. Six of 26 lines bore the Thy-1.2 antigen. Ia8 and Thy-1.2 antigens were mutually exclusive on the cell lines studied. The strain of virus used to induce the leukemia, the H-2 type of the cells, and the techniques of leukemia cell propagation all appeared to influence the antigenic characteristics of the cell lines obtained. Production of infectious murine leukemia virus in vitro and expression of leukemia virus-induced membrane antigens did not appear to correlate with the presence of I8 or Thy-1.2 antigens or with the H-2 type of the cells.", "contents": "Characterization of Ia8 antigen, thy-1.2 antigen, complement receptors, and virus production in a group of murine virus-induced leukemia cell lines. Ia8, a cell membrane antigen controlled by gene(s) located in the I region of the H-2 complex, was found on 9 of 26 murine leukemia cell lines. Iaddition, 3 of the 9 Ia8-bearing lines had a membrane receptor for antigen-antibody-complement complexes. Six of 26 lines bore the Thy-1.2 antigen. Ia8 and Thy-1.2 antigens were mutually exclusive on the cell lines studied. The strain of virus used to induce the leukemia, the H-2 type of the cells, and the techniques of leukemia cell propagation all appeared to influence the antigenic characteristics of the cell lines obtained. Production of infectious murine leukemia virus in vitro and expression of leukemia virus-induced membrane antigens did not appear to correlate with the presence of I8 or Thy-1.2 antigens or with the H-2 type of the cells."}
{"id": "PMID:185296", "title": "Independent effects of IgG and complement upon human polymorphonuclear leukocyte function.", "content": "Particle ingestion by polymorphonuclear leukocytes (PMN) is promoted by cell surface recognition and binding of fragments of the third component of complement (C3) and Fc regions of certain immunoglobulin (IgG) molecules. In order to determine the influence of these specific ligandsurface membrane interactions upon other PMN functions, we have employed nonphagocytosable particles (serum-treated Sepharose beads) coated with fragments of C3 and/or IgG, and have investigated whether these provide a sufficient stimulus for the metabolic changes and degranulation that ordinarly accompany phagocytosis by PMN. Sepharose 4B activates complement in fresh normal serum and consequently is coated with fragments of C3 (confirmed by immunoelectrophoretic evidence of factor B and C3 conversion and by immunofluorescence). Adsorbed IgG could be removed from serum-treated Sepharose by boiling in 2 M NaCl without significantly influencing bound complement. We have found that normal human PMN recognize and adhere to Sepharose beads coated with fragments of C3 and consequently are stimulated to increase their oxidative metabolism (measured as superoxide anion generation). This PMN response occurred in the absence of IgG but could be amplified if this immunoglobulin was also present on the bead surfaces. Both adherence and metabolic stimulation could be blocked by treatment of the beads with F(ab)2 anti-C3. In contrast to metabolic stimulation, degranulation (selective extracellular release of lysosomal constituents) was observed only when PMN encountered both C3 fragments and IgG on the beads. This response could be blocked by treating beads with either F(ab)2 anti-C3 or F(ab)2 anti-IgG. These results indicate that cell surface stimulation of PMN is not an \"all or none\" phenomenon and that certain vital functions of these cells may be mediated or modulated independently by immunoglobulins and complement.", "contents": "Independent effects of IgG and complement upon human polymorphonuclear leukocyte function. Particle ingestion by polymorphonuclear leukocytes (PMN) is promoted by cell surface recognition and binding of fragments of the third component of complement (C3) and Fc regions of certain immunoglobulin (IgG) molecules. In order to determine the influence of these specific ligandsurface membrane interactions upon other PMN functions, we have employed nonphagocytosable particles (serum-treated Sepharose beads) coated with fragments of C3 and/or IgG, and have investigated whether these provide a sufficient stimulus for the metabolic changes and degranulation that ordinarly accompany phagocytosis by PMN. Sepharose 4B activates complement in fresh normal serum and consequently is coated with fragments of C3 (confirmed by immunoelectrophoretic evidence of factor B and C3 conversion and by immunofluorescence). Adsorbed IgG could be removed from serum-treated Sepharose by boiling in 2 M NaCl without significantly influencing bound complement. We have found that normal human PMN recognize and adhere to Sepharose beads coated with fragments of C3 and consequently are stimulated to increase their oxidative metabolism (measured as superoxide anion generation). This PMN response occurred in the absence of IgG but could be amplified if this immunoglobulin was also present on the bead surfaces. Both adherence and metabolic stimulation could be blocked by treatment of the beads with F(ab)2 anti-C3. In contrast to metabolic stimulation, degranulation (selective extracellular release of lysosomal constituents) was observed only when PMN encountered both C3 fragments and IgG on the beads. This response could be blocked by treating beads with either F(ab)2 anti-C3 or F(ab)2 anti-IgG. These results indicate that cell surface stimulation of PMN is not an \"all or none\" phenomenon and that certain vital functions of these cells may be mediated or modulated independently by immunoglobulins and complement."}
{"id": "PMID:185297", "title": "Lysis of tumor cells by antibody and complement. VII. Complement-dependent 86Rb release--a nonlethal event?", "content": "The guinea pig hepatoma (line-1) treated with anti-Forssman antibody (TA) and GPC sequentially released 86Rb, 14C from 14C aminoidobutyric acid and failed to exclude trypan blue. Incubation of TA with fluid phase GPC for 1 min caused maximal 86Rb release; however, if the GPC was removed at this time, the cells were not subsequently killed. Using a number of naturally occurring human sera deficient in a complement component we have shown 86Rb release requires the binding of the complement components 1 through 8, but there was no absolute requirement for C9. Irreversible damage to the cell as measured by 14C AIB release or uptake of trypan blue required the complete sequence of complete sequence of complement components. These observations indicate that 86Rb release is not a relible indicator cytotoxicity.", "contents": "Lysis of tumor cells by antibody and complement. VII. Complement-dependent 86Rb release--a nonlethal event? The guinea pig hepatoma (line-1) treated with anti-Forssman antibody (TA) and GPC sequentially released 86Rb, 14C from 14C aminoidobutyric acid and failed to exclude trypan blue. Incubation of TA with fluid phase GPC for 1 min caused maximal 86Rb release; however, if the GPC was removed at this time, the cells were not subsequently killed. Using a number of naturally occurring human sera deficient in a complement component we have shown 86Rb release requires the binding of the complement components 1 through 8, but there was no absolute requirement for C9. Irreversible damage to the cell as measured by 14C AIB release or uptake of trypan blue required the complete sequence of complete sequence of complement components. These observations indicate that 86Rb release is not a relible indicator cytotoxicity."}
{"id": "PMID:185298", "title": "Characterization of Ia antigens in mouse serum.", "content": "Sera obtained from normal B10.BR mice were shown to inhibit selectively a specific anti-Ia alloantiserum. Partial purification of the Ia antigenic activity was accomplished by isolation of the high density lipoproteins from these sera by fractional precipitation with sodium phosphotungstate and MgCL2. Both H-2.23 and Iak antigens present in this high density lipoprotein fraction were completely adsorbed by rabbit anit-rat beta2-microglobulin immunoadsorbents, whereas specific anti-H-2.23 immunoadsorbents removed only the H-2 activity. These data deomnstrate that Ia antigens, like H-2 antigens in the sera of B10.BR mice are associated with high density lipoproteins and further suggest that both H-2 and Ia antigens are associated with a beta2-microglobulin-like molecule.", "contents": "Characterization of Ia antigens in mouse serum. Sera obtained from normal B10.BR mice were shown to inhibit selectively a specific anti-Ia alloantiserum. Partial purification of the Ia antigenic activity was accomplished by isolation of the high density lipoproteins from these sera by fractional precipitation with sodium phosphotungstate and MgCL2. Both H-2.23 and Iak antigens present in this high density lipoprotein fraction were completely adsorbed by rabbit anit-rat beta2-microglobulin immunoadsorbents, whereas specific anti-H-2.23 immunoadsorbents removed only the H-2 activity. These data deomnstrate that Ia antigens, like H-2 antigens in the sera of B10.BR mice are associated with high density lipoproteins and further suggest that both H-2 and Ia antigens are associated with a beta2-microglobulin-like molecule."}
{"id": "PMID:185301", "title": "Effect of neutral red and light on Herpesvirus hominis type 1 in cell culture.", "content": "Various concentrations of neutral red were added to monolayers of muscle-skin fibroblasts after adsorption of Herpesvirus hominis type 1. The concentration necessary to reduce plaque counts was found to be 10(-5.5) M. At the same time, the minimal toxic concentration of neutral red for muscle-skin fibroblasts was determined by the concentration that reduced the plaques of a challenge virus, vesicular stomatitis virus, that was applied after treatment with neutral red and light. The minimal toxic concentration was found to be 10(-5) M. Thus, the effective concentration of neutral red for H. hominis in tissue culture appears to be only slightly less than the minimal toxic concentration. The concentrations used for clinical trials in humans have been 10(3)-10(4) times this amount. Any observed efficacy of such treatment may be a reflection of cell toxicity.", "contents": "Effect of neutral red and light on Herpesvirus hominis type 1 in cell culture. Various concentrations of neutral red were added to monolayers of muscle-skin fibroblasts after adsorption of Herpesvirus hominis type 1. The concentration necessary to reduce plaque counts was found to be 10(-5.5) M. At the same time, the minimal toxic concentration of neutral red for muscle-skin fibroblasts was determined by the concentration that reduced the plaques of a challenge virus, vesicular stomatitis virus, that was applied after treatment with neutral red and light. The minimal toxic concentration was found to be 10(-5) M. Thus, the effective concentration of neutral red for H. hominis in tissue culture appears to be only slightly less than the minimal toxic concentration. The concentrations used for clinical trials in humans have been 10(3)-10(4) times this amount. Any observed efficacy of such treatment may be a reflection of cell toxicity."}
{"id": "PMID:185302", "title": "Inter- and intralaboratory variability in antibiotic susceptibility tests with Pseudomonas aeruginosa and Enterobacteriaceae.", "content": "A two-phase collaboratice study was designed for definition of the extent to which results of disk diffusion tests can be reproduced. Two currently recommended techniques, the Kirby-Bauer method and the agar overlay method, were used. Of special concern were tests of Pseudomonas aeruginosa with moderate susceptibility to carbenicillin; gentamicin, tobramycin, polymyxin B, and colistin were also tested with P. aeruginosa as well as with Klebsiella pneumoniae, Escherichia coli, and Proteus species. The agar overlay method tended to give zones that were somewhat smaller than those given by the Kirby-Bauer method. Both disk methods demonstrated an excellent degree of reproducibility, being at least as reproducible as the standard agar dilution technique for measurement of minimal inhibitory concentrations. Slight changes in carbenicillin disk potency affected the zones of inhibition around P. aeruginosa more than those around susceptible E. coli. This fact suggests that a standard strain of P. aeruginosa would be advantageous for quality control of carbenicillin disk tests.", "contents": "Inter- and intralaboratory variability in antibiotic susceptibility tests with Pseudomonas aeruginosa and Enterobacteriaceae. A two-phase collaboratice study was designed for definition of the extent to which results of disk diffusion tests can be reproduced. Two currently recommended techniques, the Kirby-Bauer method and the agar overlay method, were used. Of special concern were tests of Pseudomonas aeruginosa with moderate susceptibility to carbenicillin; gentamicin, tobramycin, polymyxin B, and colistin were also tested with P. aeruginosa as well as with Klebsiella pneumoniae, Escherichia coli, and Proteus species. The agar overlay method tended to give zones that were somewhat smaller than those given by the Kirby-Bauer method. Both disk methods demonstrated an excellent degree of reproducibility, being at least as reproducible as the standard agar dilution technique for measurement of minimal inhibitory concentrations. Slight changes in carbenicillin disk potency affected the zones of inhibition around P. aeruginosa more than those around susceptible E. coli. This fact suggests that a standard strain of P. aeruginosa would be advantageous for quality control of carbenicillin disk tests."}
{"id": "PMID:185303", "title": "Differential sensitivity of herpes simplex virus types 1 and 2 to human interferon: antiviral effects of interferon plus 9-beta-D-arabinofuranosyladenine.", "content": "With use of a standard assay for antiviral compounds, in which the compound to be tested is added after absorption of virus, the minimal inhibitory concentration (MIC) of human interferon for several strain of herpes simplex virus type 2 (HSV-2) is five to 10 times greater than it is for two strains of herpes simplex virus type 1 (HSV-1). This differential susceptibility of HSV types to interferon is found whether tests are done with a liquid overlay and microtiter plates or with agarose overlays and appears to be a distinguishing biological marker. When the MIC of interferon is tested by microtiter or agarose methods and interferon is allowed to incubate for 24 hr before virus is added, values for HSV-1 and HSV-2 are similar and much smaller in magnitude. These results support earlier data indicating that adenine arabinoside and interferon are synergistic against herpes simplex virus type 1 in vitro and indicate that these agents are additive but not synergistic against herpes simplex virus type 2.", "contents": "Differential sensitivity of herpes simplex virus types 1 and 2 to human interferon: antiviral effects of interferon plus 9-beta-D-arabinofuranosyladenine. With use of a standard assay for antiviral compounds, in which the compound to be tested is added after absorption of virus, the minimal inhibitory concentration (MIC) of human interferon for several strain of herpes simplex virus type 2 (HSV-2) is five to 10 times greater than it is for two strains of herpes simplex virus type 1 (HSV-1). This differential susceptibility of HSV types to interferon is found whether tests are done with a liquid overlay and microtiter plates or with agarose overlays and appears to be a distinguishing biological marker. When the MIC of interferon is tested by microtiter or agarose methods and interferon is allowed to incubate for 24 hr before virus is added, values for HSV-1 and HSV-2 are similar and much smaller in magnitude. These results support earlier data indicating that adenine arabinoside and interferon are synergistic against herpes simplex virus type 1 in vitro and indicate that these agents are additive but not synergistic against herpes simplex virus type 2."}
{"id": "PMID:185306", "title": "Defective initiation of the metabolic stimulation in phagocytizing granulocytes: a new congenital defect.", "content": "Two patients suffering from recurrent bacterial infections were studied: a boy and a girl from one family, children of apparently healthy parents. The granulocytes of these patients were capable of normal ingestion of latex particles and DNA-anti-DNA immune complexes. When the metabolic changes in these granulocytes during phagocytosis of latex particles were studied, however, no stimulation of oxygen consumption, superoxide production, or hexose monophosphate shunt activity could be observed. Moreover, zymosan particles were not iodinated. These findings are comparable to those found in chronic granulomatous disease. In sharp contrast to the observations in this latter disease, however, a completely normal stimulation of cell metabolism was found after phagocytosis of IgG-coated latex particles or IgG aggregates. Since latex and IgG-coated latex were equally well ingested, this means that the absence of metabolic stimulation after uptake of tatexf metabolic stimulation after uptake of latex must be due to a defect in the triggering of the oxidative burst. As far as we know, this is the first time that a defect in the triggering of the metabolic stimulation during phagocytosis could be demonstrated. Moreover, these finding suggest that adherence and subsequent ingestion of particles are in themselves not sufficient for the metabolic stimulation of granulocytes.", "contents": "Defective initiation of the metabolic stimulation in phagocytizing granulocytes: a new congenital defect. Two patients suffering from recurrent bacterial infections were studied: a boy and a girl from one family, children of apparently healthy parents. The granulocytes of these patients were capable of normal ingestion of latex particles and DNA-anti-DNA immune complexes. When the metabolic changes in these granulocytes during phagocytosis of latex particles were studied, however, no stimulation of oxygen consumption, superoxide production, or hexose monophosphate shunt activity could be observed. Moreover, zymosan particles were not iodinated. These findings are comparable to those found in chronic granulomatous disease. In sharp contrast to the observations in this latter disease, however, a completely normal stimulation of cell metabolism was found after phagocytosis of IgG-coated latex particles or IgG aggregates. Since latex and IgG-coated latex were equally well ingested, this means that the absence of metabolic stimulation after uptake of tatexf metabolic stimulation after uptake of latex must be due to a defect in the triggering of the oxidative burst. As far as we know, this is the first time that a defect in the triggering of the metabolic stimulation during phagocytosis could be demonstrated. Moreover, these finding suggest that adherence and subsequent ingestion of particles are in themselves not sufficient for the metabolic stimulation of granulocytes."}
{"id": "PMID:185307", "title": "Abnormal pattern of bactericidal activity of neutrophils deficient in granules, myeloperoxidase, and alkaline phosphatase.", "content": "The morphology, cytochemistry, metabolism, and bactericidal function of neutrophilic polymorphonuclear leukocytes (PMN) from a patient with subacute myelogenous leukemia were evaluated. The patient's mature PMN were deficient in granules and staining reactivity for myeloperoxidase (MPO) and alkaline phosphatase (LAP). These cells killed Staphylococcus aureus in an abnormal pattern when they were challenged with various increasing multiples of bacteria per neutrophil. At a low ratio of challenge (1.25 bacteria per neutrophil) the MPO-LAP-deficient PMN killed only 18 +/- 6 per cent (mean +/- 1 S.D.) (normal, 79 +/- 7) of the initial bacterial inoculum. As the PMN were challenged with higher ratios of bacteria per cell, the bactericidal effectiveness of the hypogranular PMN improved. At a 50:1 ratio the patient's cells killed within the normal range (28 +/- 10 per cent vs. normal of 48 +/- [mean +/- 1 S.D.]). Although rates of glucose oxidation and oxygen consumption by patient or control PMN stimulated with comparable ratios of heat-killed bacteria were the same, only minimal metabolic enhancement was produced in the MPO-LAP-deficient PMN by lower ratios. In contrast, higher ratios produced a marked increase in both of these metabolic activities indicating a major metabolic response to multiple ingestions by the patient's PMN. These observations may reflect the activation of compensatory microbicidal mechanisms available to the MPO-LAP-deficient PMN only when challenged by large multiples of bacteria.", "contents": "Abnormal pattern of bactericidal activity of neutrophils deficient in granules, myeloperoxidase, and alkaline phosphatase. The morphology, cytochemistry, metabolism, and bactericidal function of neutrophilic polymorphonuclear leukocytes (PMN) from a patient with subacute myelogenous leukemia were evaluated. The patient's mature PMN were deficient in granules and staining reactivity for myeloperoxidase (MPO) and alkaline phosphatase (LAP). These cells killed Staphylococcus aureus in an abnormal pattern when they were challenged with various increasing multiples of bacteria per neutrophil. At a low ratio of challenge (1.25 bacteria per neutrophil) the MPO-LAP-deficient PMN killed only 18 +/- 6 per cent (mean +/- 1 S.D.) (normal, 79 +/- 7) of the initial bacterial inoculum. As the PMN were challenged with higher ratios of bacteria per cell, the bactericidal effectiveness of the hypogranular PMN improved. At a 50:1 ratio the patient's cells killed within the normal range (28 +/- 10 per cent vs. normal of 48 +/- [mean +/- 1 S.D.]). Although rates of glucose oxidation and oxygen consumption by patient or control PMN stimulated with comparable ratios of heat-killed bacteria were the same, only minimal metabolic enhancement was produced in the MPO-LAP-deficient PMN by lower ratios. In contrast, higher ratios produced a marked increase in both of these metabolic activities indicating a major metabolic response to multiple ingestions by the patient's PMN. These observations may reflect the activation of compensatory microbicidal mechanisms available to the MPO-LAP-deficient PMN only when challenged by large multiples of bacteria."}
{"id": "PMID:185309", "title": "Purification and characterization of Leydig cells from rat testes.", "content": "An LH-responsive Leydig cell preparation (containing 6+/-2% Leydig cells) was obtained by collagenase treatment of rat testis. Centrifugation of this cell preparation through a 13% Ficoll solution for 10 min at 1500 g resulted in a four times purification of the Leydig cells, with a concomitant increases in steroidogenic activity. Addition of 0-2% albumin to the 13% Ficoll solution, adjusted to 280 mosmol/l, resulted in a further twofold purification of the Leydig cells paralleled by a twofold increase in steroidogenic activity. Centrifugation of these Ficoll-albumin-purified Leydig cells through a 6% dextran solution for 2 min at 100 g resulted in a further 1-7 times purification of the Leydig cells. A combination of the two centrifugation steps resulted in a 12-5 times purification of Leydig cells compared with the original crude cell suspension, while an increase in steroidogenic activity of 22-5 times was obtained. This final cell preparation contained 59 +/- 17% Leydig cells (mean +/- S.D., n = 6). The recovery of Leydig cells was 29%. Collagenase treatment of testes deficient in spermatogenesis resulted in a cell preparation with the same steroidogenic activity as Ficoll-purified cells from normal testes. Centrifugation of these cells through a 13% Ficoll solution gave only a limited increase in the steroidogenic activity. Isopycnic centrifugation of the crude cell preparation on a discontinous Ficoll metrizoate gradient resulted in two discrete peaks of Leydig cells, one peak at a density of 1-039-1-055 g/ml and one at a density of 1-068-1-088 g/ml. Both types of cells produced testosterone. In the presence of LH, cyclic AMP production in both types of Leydig cells increased, but testosterone production was only increased by LH in the \"denser\" Leydig cells and not in the \"light\" Leydig cells. No difference in sensitivity to LH could be observed between the Leydig cell preparations of different purity. Using a 60 min pre-incubation period the highest testosterone response was obtained with 100-1000 ng LH/ml. The same maximum testosterone response was obtained with 10-100 ng LH/ml when the pre-incubation period was omitted.", "contents": "Purification and characterization of Leydig cells from rat testes. An LH-responsive Leydig cell preparation (containing 6+/-2% Leydig cells) was obtained by collagenase treatment of rat testis. Centrifugation of this cell preparation through a 13% Ficoll solution for 10 min at 1500 g resulted in a four times purification of the Leydig cells, with a concomitant increases in steroidogenic activity. Addition of 0-2% albumin to the 13% Ficoll solution, adjusted to 280 mosmol/l, resulted in a further twofold purification of the Leydig cells paralleled by a twofold increase in steroidogenic activity. Centrifugation of these Ficoll-albumin-purified Leydig cells through a 6% dextran solution for 2 min at 100 g resulted in a further 1-7 times purification of the Leydig cells. A combination of the two centrifugation steps resulted in a 12-5 times purification of Leydig cells compared with the original crude cell suspension, while an increase in steroidogenic activity of 22-5 times was obtained. This final cell preparation contained 59 +/- 17% Leydig cells (mean +/- S.D., n = 6). The recovery of Leydig cells was 29%. Collagenase treatment of testes deficient in spermatogenesis resulted in a cell preparation with the same steroidogenic activity as Ficoll-purified cells from normal testes. Centrifugation of these cells through a 13% Ficoll solution gave only a limited increase in the steroidogenic activity. Isopycnic centrifugation of the crude cell preparation on a discontinous Ficoll metrizoate gradient resulted in two discrete peaks of Leydig cells, one peak at a density of 1-039-1-055 g/ml and one at a density of 1-068-1-088 g/ml. Both types of cells produced testosterone. In the presence of LH, cyclic AMP production in both types of Leydig cells increased, but testosterone production was only increased by LH in the \"denser\" Leydig cells and not in the \"light\" Leydig cells. No difference in sensitivity to LH could be observed between the Leydig cell preparations of different purity. Using a 60 min pre-incubation period the highest testosterone response was obtained with 100-1000 ng LH/ml. The same maximum testosterone response was obtained with 10-100 ng LH/ml when the pre-incubation period was omitted."}
{"id": "PMID:185310", "title": "Stimulation of intra-uterine growth in rat by alpha-melanocyte-stimulating hormone.", "content": "We have studied whether endogenous alpha-MSH has a function in stimulating intra-uterine growth in the rat. The approach used was to determine whether or not this hormone is present during the intra-uterine growth spurt, and if binding of endogenous foetal alpha-MSH by antibodies would inhibit this growth. Antibodies against alpha-MSH or ACTH 1-24, either purified or non-purified, induced immunofluorescence in the intermediate lobe of adult male control rats. Using purified anti-alpha-MSH, fluorescence appeared in the foetal intermediate lobe on day 18 of pregnancy, the day that biologically active MSH was first seen. A negative correlation was observed between the pituitary MSH content and foetal body weight only on day 19 of pregnancy. Injection of purified anti-alpha-MSH induced a drop in foetal body weight, but no effect on placental weight was observed. Purified anti-acth 1-24 had no effect upon body weight but caused an increase in placental weight. These results support our previous findings and indicate that endogenous MSH has a function in the stimulation of foetal growth.", "contents": "Stimulation of intra-uterine growth in rat by alpha-melanocyte-stimulating hormone. We have studied whether endogenous alpha-MSH has a function in stimulating intra-uterine growth in the rat. The approach used was to determine whether or not this hormone is present during the intra-uterine growth spurt, and if binding of endogenous foetal alpha-MSH by antibodies would inhibit this growth. Antibodies against alpha-MSH or ACTH 1-24, either purified or non-purified, induced immunofluorescence in the intermediate lobe of adult male control rats. Using purified anti-alpha-MSH, fluorescence appeared in the foetal intermediate lobe on day 18 of pregnancy, the day that biologically active MSH was first seen. A negative correlation was observed between the pituitary MSH content and foetal body weight only on day 19 of pregnancy. Injection of purified anti-alpha-MSH induced a drop in foetal body weight, but no effect on placental weight was observed. Purified anti-acth 1-24 had no effect upon body weight but caused an increase in placental weight. These results support our previous findings and indicate that endogenous MSH has a function in the stimulation of foetal growth."}
{"id": "PMID:185312", "title": "Glycerol release in vitro from adipose tissue of obese (ob/ob) mice treated with thyroid hormones.", "content": "Glycerol release from adipose tissue of adult genetically obese (ob/ob) mice was greater than that from adipose tissue of lean litter-mates. However, a higher concentration of adrenaline was required to stimulate lipolysis in ob/ob adipose tissue. Since oxygen consumption and the uptake of radioactive iodine by the thyroid were reduced and the biological half-life of thyroidal radio-iodine was lengthened, it is suggested that ob/ob mice are hypothyroid. The poor sensitivity of ob/ob adipose tissue to low doses of adrenaline was improved by treatment with either tri-iodothyronine or thyroxine. The lipolytic responses to both dibutyryl 3':5'-cyclic adenosine monophosphate and aminophylline were enhanced in thyroid hormone-treated lean and ob/ob mice. A higher dose of tri-iodothyronine was required to enhance lipolysis in ob/ob mice than in lean controls. The possibility that hypothyroidism is responsible for the change in response of ob/ob adipose tissue to lipolytic hormones is discussed.", "contents": "Glycerol release in vitro from adipose tissue of obese (ob/ob) mice treated with thyroid hormones. Glycerol release from adipose tissue of adult genetically obese (ob/ob) mice was greater than that from adipose tissue of lean litter-mates. However, a higher concentration of adrenaline was required to stimulate lipolysis in ob/ob adipose tissue. Since oxygen consumption and the uptake of radioactive iodine by the thyroid were reduced and the biological half-life of thyroidal radio-iodine was lengthened, it is suggested that ob/ob mice are hypothyroid. The poor sensitivity of ob/ob adipose tissue to low doses of adrenaline was improved by treatment with either tri-iodothyronine or thyroxine. The lipolytic responses to both dibutyryl 3':5'-cyclic adenosine monophosphate and aminophylline were enhanced in thyroid hormone-treated lean and ob/ob mice. A higher dose of tri-iodothyronine was required to enhance lipolysis in ob/ob mice than in lean controls. The possibility that hypothyroidism is responsible for the change in response of ob/ob adipose tissue to lipolytic hormones is discussed."}
{"id": "PMID:185314", "title": "Effect of bilateral adrenalectomy and corticosteroid therapy on the secretion of corticotrophin-releasing factor activity from the hypothalamus of the rat in vitro.", "content": "The rat hypothalamus in vitro preparation was used to investigate the effect of bilateral adrenalectomy, with and without replacement therapy, on the release of corticotrophin-releasing factor(CRF). Corticotrophin-releasing factor was estimated using 48 h basal hypothalamic lesioned assay rats and corticosterone production of excised adrenals was used as the end point. Bilateral adrenalectomy resulted in depletion of hypothalamic CRF content within the first 2 h after the operation but this effect was prevented by replacement therapy with corticosterone. Thereafter, the hypothalamic CRF content returned to values not significantly different from the intact control level. Bilateral adrenalectomy caused an increase in both basal and acetylcholine-induced release of CRF and it is suggested that corticosteroids exert a negative feedback effect on the hypothalamus.", "contents": "Effect of bilateral adrenalectomy and corticosteroid therapy on the secretion of corticotrophin-releasing factor activity from the hypothalamus of the rat in vitro. The rat hypothalamus in vitro preparation was used to investigate the effect of bilateral adrenalectomy, with and without replacement therapy, on the release of corticotrophin-releasing factor(CRF). Corticotrophin-releasing factor was estimated using 48 h basal hypothalamic lesioned assay rats and corticosterone production of excised adrenals was used as the end point. Bilateral adrenalectomy resulted in depletion of hypothalamic CRF content within the first 2 h after the operation but this effect was prevented by replacement therapy with corticosterone. Thereafter, the hypothalamic CRF content returned to values not significantly different from the intact control level. Bilateral adrenalectomy caused an increase in both basal and acetylcholine-induced release of CRF and it is suggested that corticosteroids exert a negative feedback effect on the hypothalamus."}
{"id": "PMID:185315", "title": "Pituitary-adrenal function in thyroparathyroidectomized male and female rats.", "content": "The influence of thyroid hormones on pituitary-adrenal function was assessed by studying several aspects of adrenocortical function approximately 30 days after thyroparathyroidectomy (TPTx). Both male and female rats showed evidence of rhythmic adrenocortical activity; peak plasma corticosterone levels occurred just before the dark phase of the lighting schedule. Only the amplitude of the rhythm appeared altered by TPTx. Peak plasma corticosterone levels in TPTx male and female animals were less (P less than 0.05) than corresponding levels in intact control rats. Both sexes showed significant responses to stress, but the morning stress response in TPTx females was less (P less than 0.01) than the stress response in intact controls. Concomitant with the reduced stress response, the adrenocortical response to exogenous ACTH was reduced in TPTx female rats.", "contents": "Pituitary-adrenal function in thyroparathyroidectomized male and female rats. The influence of thyroid hormones on pituitary-adrenal function was assessed by studying several aspects of adrenocortical function approximately 30 days after thyroparathyroidectomy (TPTx). Both male and female rats showed evidence of rhythmic adrenocortical activity; peak plasma corticosterone levels occurred just before the dark phase of the lighting schedule. Only the amplitude of the rhythm appeared altered by TPTx. Peak plasma corticosterone levels in TPTx male and female animals were less (P less than 0.05) than corresponding levels in intact control rats. Both sexes showed significant responses to stress, but the morning stress response in TPTx females was less (P less than 0.01) than the stress response in intact controls. Concomitant with the reduced stress response, the adrenocortical response to exogenous ACTH was reduced in TPTx female rats."}
{"id": "PMID:185316", "title": "Mouse mammary tumor virus in hybrids from strains C57BL and GR: breeding test of backcross segregants.", "content": "F1 and F2 and first backcross hybrids and second backcross families of the high mammary tumor incidence strain GR and the low incidence strain C57BL were examined for the segregation of mouse mammary tumor viral (MMTV) expression. Although GR has been reported to transmit MMTV as a single dominant gene, several lines of evidence suggest there are multiple genetic factors that influence MMTV expression, MMTV expression as measured by double antibody radioimmunoassay for MMTV p14 segregated in 106 first backcross progeny at a 60:40 ratio, intermediate between what would be expected for either a single or two gene hypothesis. In female second backcross progeny of either male or female first backcross, a heterogeneous pattern of expression was noted that does not fit any simple Mendalian pattern. From an analysis of serial lactations of first backcross and second backcross families, it appears that all hybrid females contain MMTV proviral information that may be expressed either at late lactations or in a variable proportion of progeny mice. These combined results are most consistent with a vertically transmitted genome regulated by multiple factors in these crosses.", "contents": "Mouse mammary tumor virus in hybrids from strains C57BL and GR: breeding test of backcross segregants. F1 and F2 and first backcross hybrids and second backcross families of the high mammary tumor incidence strain GR and the low incidence strain C57BL were examined for the segregation of mouse mammary tumor viral (MMTV) expression. Although GR has been reported to transmit MMTV as a single dominant gene, several lines of evidence suggest there are multiple genetic factors that influence MMTV expression, MMTV expression as measured by double antibody radioimmunoassay for MMTV p14 segregated in 106 first backcross progeny at a 60:40 ratio, intermediate between what would be expected for either a single or two gene hypothesis. In female second backcross progeny of either male or female first backcross, a heterogeneous pattern of expression was noted that does not fit any simple Mendalian pattern. From an analysis of serial lactations of first backcross and second backcross families, it appears that all hybrid females contain MMTV proviral information that may be expressed either at late lactations or in a variable proportion of progeny mice. These combined results are most consistent with a vertically transmitted genome regulated by multiple factors in these crosses."}
{"id": "PMID:185317", "title": "Normal rabbit alveolar macrophages. I. The phagocytosis of tubular myelin.", "content": "Normal rabbit alveolar macrophages are engorged with large, dense inclusions which contain whorls of myelin figures, suggesting an exogenous source of polar lipids in their diet. One contributory source of such lipids is surfactant, since macrophages were seen ingesting tubular myelin and vacuoles containing remnants of it were found in the cytoplasm. Thus, as indicated previously in kinetic studies, it appears that alveolar macrophages participate in the turnover of surfactant. However, the relative importance of the macrophage in comparison to other pathways of surfactant removal remains to be determined. It is also noteworthy that although tubular myelin and myelin figures were abundant in the fixative used to wash out the lungs, bacteria were not found in it or in the macrophages. Thus, removal of obsolete surfactant may prove to be one of the mojor endocytic functions of alveolar macrophages.", "contents": "Normal rabbit alveolar macrophages. I. The phagocytosis of tubular myelin. Normal rabbit alveolar macrophages are engorged with large, dense inclusions which contain whorls of myelin figures, suggesting an exogenous source of polar lipids in their diet. One contributory source of such lipids is surfactant, since macrophages were seen ingesting tubular myelin and vacuoles containing remnants of it were found in the cytoplasm. Thus, as indicated previously in kinetic studies, it appears that alveolar macrophages participate in the turnover of surfactant. However, the relative importance of the macrophage in comparison to other pathways of surfactant removal remains to be determined. It is also noteworthy that although tubular myelin and myelin figures were abundant in the fixative used to wash out the lungs, bacteria were not found in it or in the macrophages. Thus, removal of obsolete surfactant may prove to be one of the mojor endocytic functions of alveolar macrophages."}
{"id": "PMID:185318", "title": "Normal rabbit alveolar macrophages. II. Their primary and secondary lysosomes as revealed by electron microscopy and cytochemistry.", "content": "In this investigation, vacuoles containing tubular myelin proved to be digestive compartments with cytochemical reactivity for acid phosphatase and arylsulfatase. These cytochemical markers identify the secondary lysosomes, known to contain enzymes capable of hydrolyzing phospholipids like surfactant. Therefore, it appears that alveolar macrophages possess the enzymatic machinery for the degradation of the tubular myelin found in their digestive vacuoles. Although it thus appears evident that alveolar macrophages participate in the turnover of surfactant, the quantitative significance of this route of disposal is undetermined. This investigation has also established that acid hydrolases, so prominently displayed in the secondary lysosomes, are also localized in the rough endoplasmic reticulum and in Golgi-endoplasmic reticulum-lysosomes (GERL). Moreover, small vesicles which are produced from GERL serve as primary lysosomes in transporting digestive enzymes to the vacuoles.", "contents": "Normal rabbit alveolar macrophages. II. Their primary and secondary lysosomes as revealed by electron microscopy and cytochemistry. In this investigation, vacuoles containing tubular myelin proved to be digestive compartments with cytochemical reactivity for acid phosphatase and arylsulfatase. These cytochemical markers identify the secondary lysosomes, known to contain enzymes capable of hydrolyzing phospholipids like surfactant. Therefore, it appears that alveolar macrophages possess the enzymatic machinery for the degradation of the tubular myelin found in their digestive vacuoles. Although it thus appears evident that alveolar macrophages participate in the turnover of surfactant, the quantitative significance of this route of disposal is undetermined. This investigation has also established that acid hydrolases, so prominently displayed in the secondary lysosomes, are also localized in the rough endoplasmic reticulum and in Golgi-endoplasmic reticulum-lysosomes (GERL). Moreover, small vesicles which are produced from GERL serve as primary lysosomes in transporting digestive enzymes to the vacuoles."}
{"id": "PMID:185321", "title": "The effects of cytochalasin and colchicine on interferon production.", "content": "The present study was undertaken to investigate the mechanism of interferon production by mouse spleen cells co-cultivated with BHK-HVJ cells, i.e. baby hamster kidney cells persistently infected with the HVJ (or Sendai) strain of para-influenza I virus. Cytochalasin B appears to inhibit an early stage in the process and colchicine a relatively late stage. It is suggested that microfilaments and microtubules may play in important role at an initial stage of interferon production in this system.", "contents": "The effects of cytochalasin and colchicine on interferon production. The present study was undertaken to investigate the mechanism of interferon production by mouse spleen cells co-cultivated with BHK-HVJ cells, i.e. baby hamster kidney cells persistently infected with the HVJ (or Sendai) strain of para-influenza I virus. Cytochalasin B appears to inhibit an early stage in the process and colchicine a relatively late stage. It is suggested that microfilaments and microtubules may play in important role at an initial stage of interferon production in this system."}
{"id": "PMID:185322", "title": "Synthesis of Sendai virus polypeptides by a cell-free extract from wheat germ.", "content": "The '18S' RNA population from Sendai virus-infected cells efficiently directed the synthesis of three virus-specific polypeptides P, NP and M, in wheat germ cell-free extracts. In agreement with previous results obtained with a reticulocyte extract, there was little or no production of virus glycopolypeptides. Analyses of tryptic peptides revealed close correspondence between the primary structures of NP and M made in vitro and the authentic virus polypeptides.", "contents": "Synthesis of Sendai virus polypeptides by a cell-free extract from wheat germ. The '18S' RNA population from Sendai virus-infected cells efficiently directed the synthesis of three virus-specific polypeptides P, NP and M, in wheat germ cell-free extracts. In agreement with previous results obtained with a reticulocyte extract, there was little or no production of virus glycopolypeptides. Analyses of tryptic peptides revealed close correspondence between the primary structures of NP and M made in vitro and the authentic virus polypeptides."}
{"id": "PMID:185323", "title": "A partial denaturation map of herpes simplex virus type 1 DNA: evidence for inversions of the unique DNA regions.", "content": "Partial denaturation maps of 30 HSV-I DNA molecules have been obtained using a procedure designed to avoid possible hydrolysis of the DNA at alkalilabile bonds. From the denaturation pattern of the long unique DNA region these molecules were divided into two groups comprised of 16 and 14 molecules. Histogram plots relating the precentage denaturation to position on the DNA for these two groups were aligned in a manner appropriate to the HSV-I genome model. It was apparent that these groups had the orientation of the long region inverted with respect to each other. Similarly, from the denaturation maps of the short unique region, the molecules were divided into two groups each comprising 15 molecules. Alignment of the histogram plots of these groups indicated that the orientation of the short region was inverted in one group relative to the other. These partial denaturation data confirm the presence of four HSV-I genome arrangements resulting from the possible combinations of inversions of the two unique DNA regions.", "contents": "A partial denaturation map of herpes simplex virus type 1 DNA: evidence for inversions of the unique DNA regions. Partial denaturation maps of 30 HSV-I DNA molecules have been obtained using a procedure designed to avoid possible hydrolysis of the DNA at alkalilabile bonds. From the denaturation pattern of the long unique DNA region these molecules were divided into two groups comprised of 16 and 14 molecules. Histogram plots relating the precentage denaturation to position on the DNA for these two groups were aligned in a manner appropriate to the HSV-I genome model. It was apparent that these groups had the orientation of the long region inverted with respect to each other. Similarly, from the denaturation maps of the short unique region, the molecules were divided into two groups each comprising 15 molecules. Alignment of the histogram plots of these groups indicated that the orientation of the short region was inverted in one group relative to the other. These partial denaturation data confirm the presence of four HSV-I genome arrangements resulting from the possible combinations of inversions of the two unique DNA regions."}
{"id": "PMID:185324", "title": "Plaque formation with influenza viruses in dog kidney cells.", "content": "Infectious influenza and parainfluenza viruses were produced as plaql passages of egg-grown viruses in MDCK monolayers. Virus titres of 10(6) to 10(11) p.f.u./ml were obtained for several A and B strains of influenza and parainfluenza viruses.", "contents": "Plaque formation with influenza viruses in dog kidney cells. Infectious influenza and parainfluenza viruses were produced as plaql passages of egg-grown viruses in MDCK monolayers. Virus titres of 10(6) to 10(11) p.f.u./ml were obtained for several A and B strains of influenza and parainfluenza viruses."}
{"id": "PMID:185325", "title": "Characterization of pig rotavirus RNA.", "content": "Pig rotavirus was purified from faeces. The RNA from this virus was resistant to pancreatic ribonuclease, indicating that it is double-stranded. When electrophoresed on polyacrylamide-agarose gels, pig rotavirus RNA migrated as 9 bands comprised of 11 or 12 RNA segments with a total mol. wt. of approx. 11 X 10(6). Co-electrophoresis experiments revealed that the RNAs from the pig virus and two isolates of the calf rotavirus were indistinguishable.", "contents": "Characterization of pig rotavirus RNA. Pig rotavirus was purified from faeces. The RNA from this virus was resistant to pancreatic ribonuclease, indicating that it is double-stranded. When electrophoresed on polyacrylamide-agarose gels, pig rotavirus RNA migrated as 9 bands comprised of 11 or 12 RNA segments with a total mol. wt. of approx. 11 X 10(6). Co-electrophoresis experiments revealed that the RNAs from the pig virus and two isolates of the calf rotavirus were indistinguishable."}
{"id": "PMID:185326", "title": "Virus-like particles in bovine sera for tissue culture.", "content": "Virus-like particles were found in nine different bovine sera for tissue culture from commercial suppliers. These particles were spherical with an overall diam. between 70 and 95 nm. After negative staining, surface projections of about 11 to 12 nm were clearly seen. One of the nine sera was positive in an Ouchterlony test with antisera against bovine viral diarrhoea virus.", "contents": "Virus-like particles in bovine sera for tissue culture. Virus-like particles were found in nine different bovine sera for tissue culture from commercial suppliers. These particles were spherical with an overall diam. between 70 and 95 nm. After negative staining, surface projections of about 11 to 12 nm were clearly seen. One of the nine sera was positive in an Ouchterlony test with antisera against bovine viral diarrhoea virus."}
{"id": "PMID:185327", "title": "Concanavalin A agglutinability of a temperature-sensitive mutant of Rous sarcoma virus.", "content": "Concanavalin A (Con A) concentration dependence of agglutinability of a mutant of Rous sarcoma virus which is temperature-sensitive for transformation was examined. Con A agglutinability of the virion was quantitatively expressed by measuring radioactivities of 60 to 70 S RNA extracted from Con A-agglutinated material. The mutant grown at a permissive temperature (35 degrees C) agglutinated at a significantly lower concentration of Con A, compared with that at a non-permissive temperature (40 degrees C).", "contents": "Concanavalin A agglutinability of a temperature-sensitive mutant of Rous sarcoma virus. Concanavalin A (Con A) concentration dependence of agglutinability of a mutant of Rous sarcoma virus which is temperature-sensitive for transformation was examined. Con A agglutinability of the virion was quantitatively expressed by measuring radioactivities of 60 to 70 S RNA extracted from Con A-agglutinated material. The mutant grown at a permissive temperature (35 degrees C) agglutinated at a significantly lower concentration of Con A, compared with that at a non-permissive temperature (40 degrees C)."}
{"id": "PMID:185328", "title": "Analysis of the RNA species isolated from defective particles of vesicular stomatitis virus.", "content": "Serial high multiplicity passage of a cloned stock of vesicular stomatitis virus was found to generate defective interfering particles containing three size classes of RNA, with sedimentaiton coefficients of 31 S, 23 S and 19 S. The 31 S and 23 S RNA species were found to be complementary to both the 12 to 18 S and 31 S size classes of VSV mRNAs. The 19 S class of RNA was found to be partially base-paired. All three RNA species were found to contain ppAp at their 5' termini.", "contents": "Analysis of the RNA species isolated from defective particles of vesicular stomatitis virus. Serial high multiplicity passage of a cloned stock of vesicular stomatitis virus was found to generate defective interfering particles containing three size classes of RNA, with sedimentaiton coefficients of 31 S, 23 S and 19 S. The 31 S and 23 S RNA species were found to be complementary to both the 12 to 18 S and 31 S size classes of VSV mRNAs. The 19 S class of RNA was found to be partially base-paired. All three RNA species were found to contain ppAp at their 5' termini."}
{"id": "PMID:185329", "title": "Effects of interferon on cell and virus growth in transformed human cell lines.", "content": "The anticellular and antiviral effects of human leukocyte interferons were studied in vitro in the transformed human embryonic cell lines. RSa and RSb. The growth of these cells was inhibited and they began to deteriorate about 48 h after treatment with 500 units/ml of interferon. When interferon was washed out within 48 h, their growth recovered gradually. The effects of interferon on cell growth depended on the amount of interferon added per cell. A subline, named IFr, was isolated which grows in the presence of 2000 units/ml of interferon, whereas growth of vesicular stomatitis virus in these cells is suppressed by 10 units/ml of interferon, just as in the parent cells. The anticellular and antiviral effects of interferon on IFr cells are discussed in relation to cell surface receptors.", "contents": "Effects of interferon on cell and virus growth in transformed human cell lines. The anticellular and antiviral effects of human leukocyte interferons were studied in vitro in the transformed human embryonic cell lines. RSa and RSb. The growth of these cells was inhibited and they began to deteriorate about 48 h after treatment with 500 units/ml of interferon. When interferon was washed out within 48 h, their growth recovered gradually. The effects of interferon on cell growth depended on the amount of interferon added per cell. A subline, named IFr, was isolated which grows in the presence of 2000 units/ml of interferon, whereas growth of vesicular stomatitis virus in these cells is suppressed by 10 units/ml of interferon, just as in the parent cells. The anticellular and antiviral effects of interferon on IFr cells are discussed in relation to cell surface receptors."}
{"id": "PMID:185330", "title": "Factors involved in the expression of cowpox virus-specific antigen in Sendai virus carrier cells.", "content": "Formation of cowpox virus-specific cell surface antigen (CPVS-ag) HVJ (Sendai virus) carrier cells compared to that in parent cells. Temperature shifts from 32 to 35 to 37 degrees C for these carrier cultures reduced this enhancing activity, making them equivalent to parent cells. The eclips phase and one-step growth of CPV in the carrier cells were shorter than in normal cells. Extracts of carrier cells exhibited a stimulating activity causing the temporary rise and subsequent lowering of CPV infectivity in their reactions with CPV in vitro, suggesting a cellular acceleration of CPV uncoating. The S-ag forming ability of these carrier cells did not decrease as much as that of parent cellsin the presence of actinomycin D or puromycin. The results indicate that persistent infection with HVJ, especially the temperature-sensitive variant, promotes the first step of intracellular growth of CPV, resulting in enhanced formation of S-ag.", "contents": "Factors involved in the expression of cowpox virus-specific antigen in Sendai virus carrier cells. Formation of cowpox virus-specific cell surface antigen (CPVS-ag) HVJ (Sendai virus) carrier cells compared to that in parent cells. Temperature shifts from 32 to 35 to 37 degrees C for these carrier cultures reduced this enhancing activity, making them equivalent to parent cells. The eclips phase and one-step growth of CPV in the carrier cells were shorter than in normal cells. Extracts of carrier cells exhibited a stimulating activity causing the temporary rise and subsequent lowering of CPV infectivity in their reactions with CPV in vitro, suggesting a cellular acceleration of CPV uncoating. The S-ag forming ability of these carrier cells did not decrease as much as that of parent cellsin the presence of actinomycin D or puromycin. The results indicate that persistent infection with HVJ, especially the temperature-sensitive variant, promotes the first step of intracellular growth of CPV, resulting in enhanced formation of S-ag."}
{"id": "PMID:185331", "title": "The abdominal ganglion of Aplysia brasiliana: a comparative morphological and electrophysiological study, with notes on A. dactylomela.", "content": "The ultrastructure and electrophysiological properties of neurons in the abdominal (visceral) ganglion of the marine opisthobranch gastropod Aplysia brasiliana have been investigated to determine whether this preparation compares favorably with the well studied A. californica for neurobiological research. In general, the topography, morphology and physiological characteristics, including synaptic connections, of neurons in this ganglion are quite similar to those of A. californica. There is close correspondence between the two animals in terms of each of the identified cells or neuronal clusters in the ganglion, including the presence of the cell L10 (interneuron I) in A. brasiliana which makes synaptic connections comparable with those in A. californica. New follower cells of this interneuron have been found in A. brasiliana. This species offers some advantages in that the connective tissue surrounding the ganglion is thinner and more transparent, making cell identification and penetration easier. A. brasiliana appears to exhibit the behaviors of A. californica that have been used in previous functional analyses of neural circuits. In addition, this species swims and exhibits a \"burrowing\" activity less commonly seen in A. californica. The rich repertoire of behaviors and accessibility of large identifiable and functionally interconnected neurons makes this species of Aplysia an excellent model preparation for future neurobiological studies. Similar, less thorough, investigations of the abdominal ganglion of A. dactylomela indicate that this species is also very similar to A. californica in terms of the identified cells in the abdominal ganglion.", "contents": "The abdominal ganglion of Aplysia brasiliana: a comparative morphological and electrophysiological study, with notes on A. dactylomela. The ultrastructure and electrophysiological properties of neurons in the abdominal (visceral) ganglion of the marine opisthobranch gastropod Aplysia brasiliana have been investigated to determine whether this preparation compares favorably with the well studied A. californica for neurobiological research. In general, the topography, morphology and physiological characteristics, including synaptic connections, of neurons in this ganglion are quite similar to those of A. californica. There is close correspondence between the two animals in terms of each of the identified cells or neuronal clusters in the ganglion, including the presence of the cell L10 (interneuron I) in A. brasiliana which makes synaptic connections comparable with those in A. californica. New follower cells of this interneuron have been found in A. brasiliana. This species offers some advantages in that the connective tissue surrounding the ganglion is thinner and more transparent, making cell identification and penetration easier. A. brasiliana appears to exhibit the behaviors of A. californica that have been used in previous functional analyses of neural circuits. In addition, this species swims and exhibits a \"burrowing\" activity less commonly seen in A. californica. The rich repertoire of behaviors and accessibility of large identifiable and functionally interconnected neurons makes this species of Aplysia an excellent model preparation for future neurobiological studies. Similar, less thorough, investigations of the abdominal ganglion of A. dactylomela indicate that this species is also very similar to A. californica in terms of the identified cells in the abdominal ganglion."}
{"id": "PMID:185332", "title": "The identification of two inhibitory cells in each segmental ganglion of the leech and studies on the ionic mechanism of the inhibitory junctional potentials produced by these cells.", "content": "The present study identifies a pair of inhibitory cells that are located on each anterolateral margin of a leech segmental ganglion. These cells, which we label as cells 119, are electrically interconnected. These cells give rise to inhibitory junctional potentials (ijp's) in contralteral longitudinal body wall muscle cells. The latencies of the ijp's following spikes in cell 119 are variable. The ijp's are caused by transient increases in premeability to the Cl- ion. Previous studies demonstrated that 5-HT causes a hyperpolarization of body wall muscle cells by increasing the permeability of muscle membrane to the Cl- ion. Accordingly, 5-HT was searched for in the 119 cell bodies, but autoradiography, fine structure, and gas chromatography-mass spectrometry gave no indication that 5-HT was present in these cells. However, the variable latencies of the ijp's may indicate that there is a neuron interposed between cell 119 and the muscle cells. If this is the case, then the interposed neuron should be analyzed for 5-HT. Further experiments to locate the terminals of cells 119 and the cell bodies of the presumed interposed neurons are thus desirable.", "contents": "The identification of two inhibitory cells in each segmental ganglion of the leech and studies on the ionic mechanism of the inhibitory junctional potentials produced by these cells. The present study identifies a pair of inhibitory cells that are located on each anterolateral margin of a leech segmental ganglion. These cells, which we label as cells 119, are electrically interconnected. These cells give rise to inhibitory junctional potentials (ijp's) in contralteral longitudinal body wall muscle cells. The latencies of the ijp's following spikes in cell 119 are variable. The ijp's are caused by transient increases in premeability to the Cl- ion. Previous studies demonstrated that 5-HT causes a hyperpolarization of body wall muscle cells by increasing the permeability of muscle membrane to the Cl- ion. Accordingly, 5-HT was searched for in the 119 cell bodies, but autoradiography, fine structure, and gas chromatography-mass spectrometry gave no indication that 5-HT was present in these cells. However, the variable latencies of the ijp's may indicate that there is a neuron interposed between cell 119 and the muscle cells. If this is the case, then the interposed neuron should be analyzed for 5-HT. Further experiments to locate the terminals of cells 119 and the cell bodies of the presumed interposed neurons are thus desirable."}
{"id": "PMID:185333", "title": "Demyelinative myelopathy in mice induced by the DA virus.", "content": "An attenuated tissue culture adapted strain of DA virus, an agent related to the Theiler murine encephalomyelitis viruses (TMEV), was used to induce a chronic myelopathy in mice. Spastic paraparesis first appeared 5 months after weanings were inoculated intracerebrally with the virus. None died as a direct result of the infection, and none improved once paretic. The major pathological change in these mice was demyelination of thoracic segments of spinal cord. No clinical illness or demyelinative pathology were detected during the first 4 months after inoculation. Encephalitic virus was present in brain and spinal cord as late as 10 months after inoculation. No neutralization antibody activity to DA virus was present in sera from 10 patients with amyotrophic lateral sclerosis, 10 with multiple sclerosis, or in 10 controls.", "contents": "Demyelinative myelopathy in mice induced by the DA virus. An attenuated tissue culture adapted strain of DA virus, an agent related to the Theiler murine encephalomyelitis viruses (TMEV), was used to induce a chronic myelopathy in mice. Spastic paraparesis first appeared 5 months after weanings were inoculated intracerebrally with the virus. None died as a direct result of the infection, and none improved once paretic. The major pathological change in these mice was demyelination of thoracic segments of spinal cord. No clinical illness or demyelinative pathology were detected during the first 4 months after inoculation. Encephalitic virus was present in brain and spinal cord as late as 10 months after inoculation. No neutralization antibody activity to DA virus was present in sera from 10 patients with amyotrophic lateral sclerosis, 10 with multiple sclerosis, or in 10 controls."}
{"id": "PMID:185334", "title": "Lipid abnormalities in hereditary neuropathy. Part I. Serum non-polar lipids.", "content": "The non-polar lipids from sera of 54 patients, with various types of hereditary motor and sensory neuropathies, and from 72 healthy subjects were evaluated. A small but highly significant decrease in the percentage of linoleate to total fatty acids in both cholesteryl ester and triglyceride fractions was found in the sera of the neuropathy patients, except in those who had dominantly inherited sensory neuropathy (HSN-I) and who had spinocerebellar degeneration with retinitis pigmentosa and other features (SpC+). A significant decrease of serum lecithin-cholesterol acyltransferase activity was also found in those patients with hereditary motor and sensory neuropathies, Type I and Type II (two types of peroneal muscular atrophy). The biochemical basis of these abnormalities is not apparent. The biochemical abnormalities reported here have been found in several neurologic disorders and hence are unlikely to be disease-specific.", "contents": "Lipid abnormalities in hereditary neuropathy. Part I. Serum non-polar lipids. The non-polar lipids from sera of 54 patients, with various types of hereditary motor and sensory neuropathies, and from 72 healthy subjects were evaluated. A small but highly significant decrease in the percentage of linoleate to total fatty acids in both cholesteryl ester and triglyceride fractions was found in the sera of the neuropathy patients, except in those who had dominantly inherited sensory neuropathy (HSN-I) and who had spinocerebellar degeneration with retinitis pigmentosa and other features (SpC+). A significant decrease of serum lecithin-cholesterol acyltransferase activity was also found in those patients with hereditary motor and sensory neuropathies, Type I and Type II (two types of peroneal muscular atrophy). The biochemical basis of these abnormalities is not apparent. The biochemical abnormalities reported here have been found in several neurologic disorders and hence are unlikely to be disease-specific."}
{"id": "PMID:185336", "title": "Spinal changes in the neuropathy of thallium poisoning. A case with neuropathological studies.", "content": "Thallium poisoning in a man of 32 years resulted in typical peripheral neuropathy, skin rash and alopecia. Post-mortem studies showed widespread loss of peripheral nerve fibres and chromatolysis in spinal neurones. The distal nature of the nerve fibre degeneration in thallium poisoning and the sensitivity of long fibres is emphasized in this case.", "contents": "Spinal changes in the neuropathy of thallium poisoning. A case with neuropathological studies. Thallium poisoning in a man of 32 years resulted in typical peripheral neuropathy, skin rash and alopecia. Post-mortem studies showed widespread loss of peripheral nerve fibres and chromatolysis in spinal neurones. The distal nature of the nerve fibre degeneration in thallium poisoning and the sensitivity of long fibres is emphasized in this case."}
{"id": "PMID:185335", "title": "Neurochemical findings in adreno-leukodystrophy.", "content": "The results of neurochemical examination of brain tissue derived from 2 cases of adreno-leukodystrophy have been presented. Both white and grey matter contained suadanophilic material. Although free fatty acid was also present, cholesteryl ester accounted for the bulk of the sudanophilic material. Total cholesterol, galactolipid and phospholipid content was reduced in both white and grey matter. The lipid loss was particularly severe from white matter indicative of considerable demyelination. Cholesterol was found to be the only major sterol present in white or grey matter. Subcellular fractionation of the diseased white matter resulted in myelin and two related fractions, one of which was very fatty and was rich in steryl ester. Morphological examination of myelin indicated loosely-packed lamellae. All of 3 fractions had adenosine 2',6'-cyclic nucleotide-3'-phosphohydrolase activity. Myein and the fraction not rich in cholesteryl ester had discernable basic protein bands when examined by polyacrylamide gel electrophoresis. Analysis of the fatty acid composition of choline and ethanolamine glycerophospholipids indicated a general increase of saturated fatty acids, relative to control values and a decrease in long-chain fatty acids. Examination of sphingomyelin fatty acids also demonstrated a loss of long-chain fatty acids. The fatty acid composition of the cholesteryl esters from white and grey matter differed. The findings indicate generalized damage to the brain, both of white and grey matter, with the damage to the white matter being much more severe. No abnormal sterol or other lipid was isolated.", "contents": "Neurochemical findings in adreno-leukodystrophy. The results of neurochemical examination of brain tissue derived from 2 cases of adreno-leukodystrophy have been presented. Both white and grey matter contained suadanophilic material. Although free fatty acid was also present, cholesteryl ester accounted for the bulk of the sudanophilic material. Total cholesterol, galactolipid and phospholipid content was reduced in both white and grey matter. The lipid loss was particularly severe from white matter indicative of considerable demyelination. Cholesterol was found to be the only major sterol present in white or grey matter. Subcellular fractionation of the diseased white matter resulted in myelin and two related fractions, one of which was very fatty and was rich in steryl ester. Morphological examination of myelin indicated loosely-packed lamellae. All of 3 fractions had adenosine 2',6'-cyclic nucleotide-3'-phosphohydrolase activity. Myein and the fraction not rich in cholesteryl ester had discernable basic protein bands when examined by polyacrylamide gel electrophoresis. Analysis of the fatty acid composition of choline and ethanolamine glycerophospholipids indicated a general increase of saturated fatty acids, relative to control values and a decrease in long-chain fatty acids. Examination of sphingomyelin fatty acids also demonstrated a loss of long-chain fatty acids. The fatty acid composition of the cholesteryl esters from white and grey matter differed. The findings indicate generalized damage to the brain, both of white and grey matter, with the damage to the white matter being much more severe. No abnormal sterol or other lipid was isolated."}
{"id": "PMID:185337", "title": "Concentric laminated bodies. Ultrastructural demonstration of muscle fiber type specificity.", "content": "Concentric laminated bodies were identified in the skeletal muscle of 3 children affected by muscle weakness and hypotonia with probable cerebral involvement. The mean Z-line and M-line widths from each of 11 muscle fibers containing the concentric laminated bodies were calculated. The mean Z-line widths were 61-81 nm and the mean M-line widths from 7 out of 11 fibers were 54-65 nm. According to our present system of fiber typing, the majority of these fibers would be classified as subtype IIB. The possible pathogenesis and fiber type specificity of the concentric laminated body is discussed.", "contents": "Concentric laminated bodies. Ultrastructural demonstration of muscle fiber type specificity. Concentric laminated bodies were identified in the skeletal muscle of 3 children affected by muscle weakness and hypotonia with probable cerebral involvement. The mean Z-line and M-line widths from each of 11 muscle fibers containing the concentric laminated bodies were calculated. The mean Z-line widths were 61-81 nm and the mean M-line widths from 7 out of 11 fibers were 54-65 nm. According to our present system of fiber typing, the majority of these fibers would be classified as subtype IIB. The possible pathogenesis and fiber type specificity of the concentric laminated body is discussed."}
{"id": "PMID:185338", "title": "Peripheral neuropathy complicating primary hyperoxaluria.", "content": "A patient with chronic renal disease due to primary hyperoxaluria developed a rapidly progressing motor neuropathy with marked impairment of nerve conduction. Pathological studies demonstrated the presence of both axonal degeneration and segmental demyelination, together with the presence of oxalate crystals within axons. It is suggested that the development of peripheral neuropathy complicating hyperoxaluria is a consequence of the increased life-span mad possible by haemodialysis.", "contents": "Peripheral neuropathy complicating primary hyperoxaluria. A patient with chronic renal disease due to primary hyperoxaluria developed a rapidly progressing motor neuropathy with marked impairment of nerve conduction. Pathological studies demonstrated the presence of both axonal degeneration and segmental demyelination, together with the presence of oxalate crystals within axons. It is suggested that the development of peripheral neuropathy complicating hyperoxaluria is a consequence of the increased life-span mad possible by haemodialysis."}
{"id": "PMID:185339", "title": "Recessive hereditary sensory neuropathy.", "content": "Clinical features in 2 cases of a recessive form of hereditary sensory neuropathy and the light and electron microscopy of sural nerve biopsy in 1 of them are described. The patients showed symptoms typical of this form of the disease; it should be stressed however that the loss of cutaneous sensation appeared to be limited to the distal parts of the lower extremities and involved all modalities of cutaneous sensation. Histological examination of sural nerve revealed a marked reduction in the number of myelinated fibres due to Wallerian-like axonal degeneration, of which various stages were represented. In addition, segmental demyelination, probably secondary to axonal changes, was seen. The unmyelinated fibres were also involved but to a lesser degree than the myelinated fibres. The observations indicate a progressive nature of the pathological process.", "contents": "Recessive hereditary sensory neuropathy. Clinical features in 2 cases of a recessive form of hereditary sensory neuropathy and the light and electron microscopy of sural nerve biopsy in 1 of them are described. The patients showed symptoms typical of this form of the disease; it should be stressed however that the loss of cutaneous sensation appeared to be limited to the distal parts of the lower extremities and involved all modalities of cutaneous sensation. Histological examination of sural nerve revealed a marked reduction in the number of myelinated fibres due to Wallerian-like axonal degeneration, of which various stages were represented. In addition, segmental demyelination, probably secondary to axonal changes, was seen. The unmyelinated fibres were also involved but to a lesser degree than the myelinated fibres. The observations indicate a progressive nature of the pathological process."}
{"id": "PMID:185340", "title": "Alteration of the maximal activity of the gluconeogenetic enzyme fructose-1,6-diphosphatase of skeletal muscle by cross-reinnervation. A histochemical and biochemical investigation of fatiguability-related aspects.", "content": "Fatiguability is a determining characteristic of different muscle fibre types. An important aspect, indirectly related to fatiguability, gluconeogenesis, was investigated by observing fructose-1,6-diphosphatase (FDP) activity in experimental models prepared in rabbits by cross-reinnervation of the fatigue-resistant m.soleus (postural muscle) and the highly fatiguable m.flexor digitorum longus (fast muscle -- m.fdl). The resultant reprogramming of the m. soleus was associated with greatly intensified FDP activity. Changes in the m.fdl 6-9 months after cross-reinnervation indicated a shift in the opposite direction. The study adds some data on the much neglected state of fatiguability to the otherwise much explored field of alien reinnervation.", "contents": "Alteration of the maximal activity of the gluconeogenetic enzyme fructose-1,6-diphosphatase of skeletal muscle by cross-reinnervation. A histochemical and biochemical investigation of fatiguability-related aspects. Fatiguability is a determining characteristic of different muscle fibre types. An important aspect, indirectly related to fatiguability, gluconeogenesis, was investigated by observing fructose-1,6-diphosphatase (FDP) activity in experimental models prepared in rabbits by cross-reinnervation of the fatigue-resistant m.soleus (postural muscle) and the highly fatiguable m.flexor digitorum longus (fast muscle -- m.fdl). The resultant reprogramming of the m. soleus was associated with greatly intensified FDP activity. Changes in the m.fdl 6-9 months after cross-reinnervation indicated a shift in the opposite direction. The study adds some data on the much neglected state of fatiguability to the otherwise much explored field of alien reinnervation."}
{"id": "PMID:185341", "title": "[Recurrent peripheral nerve palsies and concomitant chronic neuropathy. Neuromusclar electrophysiologic study and neuropathologic examination: apropos of 5 cases].", "content": "The authors report 5 personal cases (3 in the same family) of patients suffering from recurrent peripheral nerve palsies usually induced by pressure and review the relevant literature. There is evidence in such cases of a mild, chronic, diffuse, subclinical neuropathy which can be recognized by electrophysiological examination. Examination of peripheral nerve biopsy material in such cases shows evidence of both axonal and Schwann cell abnormalities with evidence of neurogenic atrophy of skeletal muscles. This chronic subclinical neuropathy which is often familial can be distinguished from other chronic primary neuropathies with or without myelin sheath proliferation and hypertrophy.", "contents": "[Recurrent peripheral nerve palsies and concomitant chronic neuropathy. Neuromusclar electrophysiologic study and neuropathologic examination: apropos of 5 cases]. The authors report 5 personal cases (3 in the same family) of patients suffering from recurrent peripheral nerve palsies usually induced by pressure and review the relevant literature. There is evidence in such cases of a mild, chronic, diffuse, subclinical neuropathy which can be recognized by electrophysiological examination. Examination of peripheral nerve biopsy material in such cases shows evidence of both axonal and Schwann cell abnormalities with evidence of neurogenic atrophy of skeletal muscles. This chronic subclinical neuropathy which is often familial can be distinguished from other chronic primary neuropathies with or without myelin sheath proliferation and hypertrophy."}
{"id": "PMID:185342", "title": "Cerebellar glioblastoma in childhood. Case report.", "content": "Ten childhood cerebellar glioblastomas have been reported previously in the world literature. The authors report a case arising de novo in a 9-year-old child and stress the rarity of this tumor.", "contents": "Cerebellar glioblastoma in childhood. Case report. Ten childhood cerebellar glioblastomas have been reported previously in the world literature. The authors report a case arising de novo in a 9-year-old child and stress the rarity of this tumor."}
{"id": "PMID:185343", "title": "myo-Inositol metabolism in the neonatal and developing rat fed a myo-inositol-free diet.", "content": "Neonatal rats of the Holtzman strain, 6 days of age, were fed a myo-inositol restricted liquid formula by gastric intubation for 10 days, after which they were fed a purified myo-inositol-free diet until they were 72 days old. No differences in weight gain were observed between myo-inositol/100 ml of formula or 150 mg myo-inositol/100 g diet. Most tissues examined from rats fed the myo-inositol deprived formula and diet had lower free myo-inositol levels than the controls with the exception of the liver. Despite reduced free and lipid-bound myo-inositol in the liver, there was no evidence of fatty liver in the young rats at any age. The cerebrum and cerebellum of myo-inositol deprived rats had normal myelination and mitochondriogenesis as judged by the levels of 2',3'-cyclic nucleotide-3'-phosphohydrolase (EC 3.1.4.1) and fumarase (EC 4.2.1.2) activity, respectively.", "contents": "myo-Inositol metabolism in the neonatal and developing rat fed a myo-inositol-free diet. Neonatal rats of the Holtzman strain, 6 days of age, were fed a myo-inositol restricted liquid formula by gastric intubation for 10 days, after which they were fed a purified myo-inositol-free diet until they were 72 days old. No differences in weight gain were observed between myo-inositol/100 ml of formula or 150 mg myo-inositol/100 g diet. Most tissues examined from rats fed the myo-inositol deprived formula and diet had lower free myo-inositol levels than the controls with the exception of the liver. Despite reduced free and lipid-bound myo-inositol in the liver, there was no evidence of fatty liver in the young rats at any age. The cerebrum and cerebellum of myo-inositol deprived rats had normal myelination and mitochondriogenesis as judged by the levels of 2',3'-cyclic nucleotide-3'-phosphohydrolase (EC 3.1.4.1) and fumarase (EC 4.2.1.2) activity, respectively."}
{"id": "PMID:185345", "title": "Neurochemical changes in Leigh's disease.", "content": "A series of children with Leigh's disease had normal hepatic pyruvate carboxylase activity, increased cerebral thiamine diphosphate, and decreased cerebral thiamine triphosphate. These thiamine esters were normal in liver. The author suggests that the histologic changes of Leigh's disease, as well as the similar changes of Wernicke's disease, could be due to a deficiency of cerebral thiamine triphosphate.", "contents": "Neurochemical changes in Leigh's disease. A series of children with Leigh's disease had normal hepatic pyruvate carboxylase activity, increased cerebral thiamine diphosphate, and decreased cerebral thiamine triphosphate. These thiamine esters were normal in liver. The author suggests that the histologic changes of Leigh's disease, as well as the similar changes of Wernicke's disease, could be due to a deficiency of cerebral thiamine triphosphate."}
{"id": "PMID:185350", "title": "Cytochemical localization of peroxidase activity in the mitochondria of Hymenolepis diminuta.", "content": "A cytochemical study of mitochondria of Hymenolepis diminuta indicates the presence of a mitochondrial peroxidase. Utilizing a 3,3'-diaminobenzidine (DAB) medium at pH 9.7, the reaction product is localized in the intracristal space, and between the inner and outer membranes of the mitochondria. No inhibitory effects are exerted on the peroxidase reaction by cyanide, azide, or aminotriazole. In addition, the mitochondria appear to have an enzyme which is cytochemically similar to vertebrate cytochrome c-oxidase. The possible physiological significance of the peroxidase is discussed.", "contents": "Cytochemical localization of peroxidase activity in the mitochondria of Hymenolepis diminuta. A cytochemical study of mitochondria of Hymenolepis diminuta indicates the presence of a mitochondrial peroxidase. Utilizing a 3,3'-diaminobenzidine (DAB) medium at pH 9.7, the reaction product is localized in the intracristal space, and between the inner and outer membranes of the mitochondria. No inhibitory effects are exerted on the peroxidase reaction by cyanide, azide, or aminotriazole. In addition, the mitochondria appear to have an enzyme which is cytochemically similar to vertebrate cytochrome c-oxidase. The possible physiological significance of the peroxidase is discussed."}
{"id": "PMID:185353", "title": "Oxidation of selected pteridine derivatives by mamalian liver xanthine oxidase and aldehyde oxidase.", "content": "Considerable information is available concerning the oxidation of pteridine derivatives by bovine milk xanthine oxidase, but few investigations have been carried out on the oxidation of such compounds by mammalian liver xanthine oxidase and the related aldehyde oxidase. Xanthine oxidase, obtained from rat liver, oxidizes a variety of substituted amino- and hydroxypteridines in a manner identical to that previously observed for milk xanthine oxidase. For example, 2-aminopteridine and its 4- and 7-hydroxy derivatives were oxidized efficiently to 2-amino-4,7-dihydroxypteridine (isoxanthopterin) by the rat liver enzyme, and 4-aminopteridine and its 2- and 7-hydroxy derivatives were oxidized to 4-amino-2,7-dihydroxypteridine.4-Hydroxypteridine and the isomeric 2- and 7-hydroxypteridines were oxidized by rat liver xanthine oxidase to 2,4,7-trihydroxypteridine. Rabbit liver aldehyde oxidase, but not rat liver xanthine oxidase, was able to catalyze the oxidation in position 7 of 2,4-diaminopteridine and its 6-methyl and 6-hydroxymethyl derivatives. 2-Aminopteridine and 4-aminopteridine were both oxidized to the corresponding 7-hydroxy derivatives in the aldehyde oxidase system; 2-amino-4-hydroxypteridine appeared to be a minor product in the oxidation of 2-aminopteridine by rabbit liver aldehyde oxidase. Both aldehyde oxidase and xanthine oxidase were able to catalyze the oxidation of 2-amino-6,7-disubstituted pteridines to the corresponding 4-hydroxy derivatives; 4-hydroxy-6,7-disubstituted pteridines were oxidized in position 2 by both enzymes. 4-Amino-6,7-disubstituted pteridines were not oxidized by either enzyme. 2-Amino-4-methylpteridine was oxidized in position 7 by aldehyde oxidase but was not an effective substrate for xanthine oxidase; 2-hydroxypteridine and 7-hydroxypteridine were not oxidized to a detectably extent by aldehyde oxidase. All oxidations mediated by xanthine oxidase were strongly inhibited by allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine), and all oxidations mediated by aldehyde oxidase were inhibited by menadione (2-methyl-1,4-naphthoquinone). Rat liver xanthine oxidase and, to a lesser extent, rabbit liver aldehyde oxidase were inhibited by 4-chloro-6,7-dimethylpteridine; 2-amino-3-pyrazinecarboxylic acid inhibited xanthine oxidase but not aldehyde oxidase. The oxidations of 2- and 4-aminopteridines by aldehyde oxidase resulted in concomitant reduction of cytochrome c.", "contents": "Oxidation of selected pteridine derivatives by mamalian liver xanthine oxidase and aldehyde oxidase. Considerable information is available concerning the oxidation of pteridine derivatives by bovine milk xanthine oxidase, but few investigations have been carried out on the oxidation of such compounds by mammalian liver xanthine oxidase and the related aldehyde oxidase. Xanthine oxidase, obtained from rat liver, oxidizes a variety of substituted amino- and hydroxypteridines in a manner identical to that previously observed for milk xanthine oxidase. For example, 2-aminopteridine and its 4- and 7-hydroxy derivatives were oxidized efficiently to 2-amino-4,7-dihydroxypteridine (isoxanthopterin) by the rat liver enzyme, and 4-aminopteridine and its 2- and 7-hydroxy derivatives were oxidized to 4-amino-2,7-dihydroxypteridine.4-Hydroxypteridine and the isomeric 2- and 7-hydroxypteridines were oxidized by rat liver xanthine oxidase to 2,4,7-trihydroxypteridine. Rabbit liver aldehyde oxidase, but not rat liver xanthine oxidase, was able to catalyze the oxidation in position 7 of 2,4-diaminopteridine and its 6-methyl and 6-hydroxymethyl derivatives. 2-Aminopteridine and 4-aminopteridine were both oxidized to the corresponding 7-hydroxy derivatives in the aldehyde oxidase system; 2-amino-4-hydroxypteridine appeared to be a minor product in the oxidation of 2-aminopteridine by rabbit liver aldehyde oxidase. Both aldehyde oxidase and xanthine oxidase were able to catalyze the oxidation of 2-amino-6,7-disubstituted pteridines to the corresponding 4-hydroxy derivatives; 4-hydroxy-6,7-disubstituted pteridines were oxidized in position 2 by both enzymes. 4-Amino-6,7-disubstituted pteridines were not oxidized by either enzyme. 2-Amino-4-methylpteridine was oxidized in position 7 by aldehyde oxidase but was not an effective substrate for xanthine oxidase; 2-hydroxypteridine and 7-hydroxypteridine were not oxidized to a detectably extent by aldehyde oxidase. All oxidations mediated by xanthine oxidase were strongly inhibited by allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine), and all oxidations mediated by aldehyde oxidase were inhibited by menadione (2-methyl-1,4-naphthoquinone). Rat liver xanthine oxidase and, to a lesser extent, rabbit liver aldehyde oxidase were inhibited by 4-chloro-6,7-dimethylpteridine; 2-amino-3-pyrazinecarboxylic acid inhibited xanthine oxidase but not aldehyde oxidase. The oxidations of 2- and 4-aminopteridines by aldehyde oxidase resulted in concomitant reduction of cytochrome c."}
{"id": "PMID:185354", "title": "Isoproterenol-induced relaxation, phosphorylase activation and cylic adenosine monophosphate levels in the polarized and depolarized rat uterus.", "content": "There is some evidence in the literature that catecholamines relax uterine and other types of smooth muscle by increasing tissue levels of cyclic adenosine monophosphate (cyclic AMP). In the present study, isoproterenol completely relaxed uterine strips obtained from estrogen-primed rats and also increased tissue levels of cyclic AMP and phosphorylase a. In uterine strips depolarized and put into contracture for 15 minutes by 127 mM K+, isoproterenol did not increase phosphorylase a or cyclic AMP but was still capable of producing relaxation. When uterine strips were exposed to the methoxy derivative of verapamil, D-600, a compound known to prevent the influx of calcium, the uterus relaxed completely without an increase in cyclic AMP. The addition of isoproterenol at this stage resulted in an increase in cyclic AMP similar to that noted in nondepolarized uterine strips. The addition of 127 mM K+ also resulted in time-dependent biochemical changes as well as contracture. Cyclic AMP was increased 3-fold after 2 minutes of K+ depolarization and phosphorylase a was increased as well. The increase in cyclic AMP was prevented by propranolol but propranolol did not affect the contracture response to K+. D-600 prevented contracture but did not affect the K+-induced increase in cyclic AMP. The data suggest that an increase in whole tissue levels of cyclic AMP are not necessary in order for isoproterenol to relax depolarized rat uterine strips. The data also suggest that intracellular calcium levels can affect the level of cyclic AMP in the rat uterus.", "contents": "Isoproterenol-induced relaxation, phosphorylase activation and cylic adenosine monophosphate levels in the polarized and depolarized rat uterus. There is some evidence in the literature that catecholamines relax uterine and other types of smooth muscle by increasing tissue levels of cyclic adenosine monophosphate (cyclic AMP). In the present study, isoproterenol completely relaxed uterine strips obtained from estrogen-primed rats and also increased tissue levels of cyclic AMP and phosphorylase a. In uterine strips depolarized and put into contracture for 15 minutes by 127 mM K+, isoproterenol did not increase phosphorylase a or cyclic AMP but was still capable of producing relaxation. When uterine strips were exposed to the methoxy derivative of verapamil, D-600, a compound known to prevent the influx of calcium, the uterus relaxed completely without an increase in cyclic AMP. The addition of isoproterenol at this stage resulted in an increase in cyclic AMP similar to that noted in nondepolarized uterine strips. The addition of 127 mM K+ also resulted in time-dependent biochemical changes as well as contracture. Cyclic AMP was increased 3-fold after 2 minutes of K+ depolarization and phosphorylase a was increased as well. The increase in cyclic AMP was prevented by propranolol but propranolol did not affect the contracture response to K+. D-600 prevented contracture but did not affect the K+-induced increase in cyclic AMP. The data suggest that an increase in whole tissue levels of cyclic AMP are not necessary in order for isoproterenol to relax depolarized rat uterine strips. The data also suggest that intracellular calcium levels can affect the level of cyclic AMP in the rat uterus."}
{"id": "PMID:185355", "title": "Regulation in the central norepinephrine neurotransmission induced in vivo by alpha adrenoceptor active drugs.", "content": "The level of the two major norepinephrine metabolites, 3-methoxy-4-hydroxyphenylglycol (MOPEG) and 3,4-dihydroxyphenylglycol (DOPEG), was estimated in the central nervous system of rats to study receptor-mediated regulation of release in vivo as reflected in biochemical changes. The norepinephrine receptor stimulating drug clonidine (0.02-0.5 mg/kg) decreased the level of endogenous total MOPEG. The accumulation of 3H-MOPEG and 3H-DOPEG was decreased by clonidine (0.5 mg/kg) regardless of whether 3H-tyrosine or 3H-dopamine was used as precursor of 3H-norepinephrine. In contrast to clonidine, the two alpha adrenoceptor blocking drugs, phenoxybenzamine (20 mg/kg) and aceperone (20 mg/kg), induced an increase in endogenous total MOPEG and also an increase in 3H-MOPEG and 3H-DOPEG regardless of the precursor used. These results indicate that clonidine decreases the release of norepinephrine in vivo and that phenoxybenzamine and aceperone increase the release of norepinephrine. Clonidine inhibited completely the effect of phenoxy benzamine or aceperone on endogenous MOPEG. On the contrary, it was not possible to block completely the effect of small doses of clonidine by pretreatment with either phenoxybenzamine, yohimbine (2 mg/kg) or a high dose of aceperone. These results indicate that clonidine may act on a different target than the alpha adrenoceptor blocking drugs. In vitro experiments with occipital cortex synaptosomes did not indicate a direct effect of clonidine on tyrosine hydroxylation in noradrenergic nerve terminals.", "contents": "Regulation in the central norepinephrine neurotransmission induced in vivo by alpha adrenoceptor active drugs. The level of the two major norepinephrine metabolites, 3-methoxy-4-hydroxyphenylglycol (MOPEG) and 3,4-dihydroxyphenylglycol (DOPEG), was estimated in the central nervous system of rats to study receptor-mediated regulation of release in vivo as reflected in biochemical changes. The norepinephrine receptor stimulating drug clonidine (0.02-0.5 mg/kg) decreased the level of endogenous total MOPEG. The accumulation of 3H-MOPEG and 3H-DOPEG was decreased by clonidine (0.5 mg/kg) regardless of whether 3H-tyrosine or 3H-dopamine was used as precursor of 3H-norepinephrine. In contrast to clonidine, the two alpha adrenoceptor blocking drugs, phenoxybenzamine (20 mg/kg) and aceperone (20 mg/kg), induced an increase in endogenous total MOPEG and also an increase in 3H-MOPEG and 3H-DOPEG regardless of the precursor used. These results indicate that clonidine decreases the release of norepinephrine in vivo and that phenoxybenzamine and aceperone increase the release of norepinephrine. Clonidine inhibited completely the effect of phenoxy benzamine or aceperone on endogenous MOPEG. On the contrary, it was not possible to block completely the effect of small doses of clonidine by pretreatment with either phenoxybenzamine, yohimbine (2 mg/kg) or a high dose of aceperone. These results indicate that clonidine may act on a different target than the alpha adrenoceptor blocking drugs. In vitro experiments with occipital cortex synaptosomes did not indicate a direct effect of clonidine on tyrosine hydroxylation in noradrenergic nerve terminals."}
{"id": "PMID:185356", "title": "Studies on the comparative pharmacology and selective toxicity of tricaine methanesulfonate: metabolism as a basis of the selective toxicity in poikilotherms.", "content": "Tricaine methanesulfonate, administered at a dose of 150 mg/kg i.p., produced a flaccid paralysis and loss of the righting reflex in a number of poikilothermic species including the frog. Leopard frogs (Rana pipiens) given 150 mg/kg i.p. regained the righting reflex at 113 +/- 28 (S.D.) minutes after injection. A similar dose administered i.p. to mice produced no apparent pharmacological response. The biological half-life (T1/2) of tricaine in frogs (R. pipiens) was about 70 minutes at temperatures of 23 and 37.5 degrees C; at 7 degrees C the T1/2 was 309 minutes. In contrast, in the mouse the drug was metabolized so rapidly that 5 minutes after i.p. administration of 5 mg of tricaine methanesulfonate (250 mg/kg) none of the unchanged drug could be recovered from the animal. It was, however, recovered quantitatively as Bratton-Marshall reacting metabolites, including m-aminobenzoic acid. Incubations of tricaine with serum from bullfrogs, mice and humans indicated that the drug was metabolized to m-aminobenzoic acid with an apparent Km of 3 X 10(-3) M for the reaction. The Vmax for incubations of the drug with bullfrog and human serum was 40 nmol/min/ml of serum, whereas in mouse serum it was 93 nmol/min/ml of serum. In vitro studies with liver homogenates showed that mouse liver metabolized tricaine 39 times more rapidly than frog liver. We conclude, therefore, that the liver is the major site of tricaine hydrolysis in mammals and that the selective toxicity of tricaine for poikilotherms is a consequence of their slower rate of hepatic biotransformation of tricaine.", "contents": "Studies on the comparative pharmacology and selective toxicity of tricaine methanesulfonate: metabolism as a basis of the selective toxicity in poikilotherms. Tricaine methanesulfonate, administered at a dose of 150 mg/kg i.p., produced a flaccid paralysis and loss of the righting reflex in a number of poikilothermic species including the frog. Leopard frogs (Rana pipiens) given 150 mg/kg i.p. regained the righting reflex at 113 +/- 28 (S.D.) minutes after injection. A similar dose administered i.p. to mice produced no apparent pharmacological response. The biological half-life (T1/2) of tricaine in frogs (R. pipiens) was about 70 minutes at temperatures of 23 and 37.5 degrees C; at 7 degrees C the T1/2 was 309 minutes. In contrast, in the mouse the drug was metabolized so rapidly that 5 minutes after i.p. administration of 5 mg of tricaine methanesulfonate (250 mg/kg) none of the unchanged drug could be recovered from the animal. It was, however, recovered quantitatively as Bratton-Marshall reacting metabolites, including m-aminobenzoic acid. Incubations of tricaine with serum from bullfrogs, mice and humans indicated that the drug was metabolized to m-aminobenzoic acid with an apparent Km of 3 X 10(-3) M for the reaction. The Vmax for incubations of the drug with bullfrog and human serum was 40 nmol/min/ml of serum, whereas in mouse serum it was 93 nmol/min/ml of serum. In vitro studies with liver homogenates showed that mouse liver metabolized tricaine 39 times more rapidly than frog liver. We conclude, therefore, that the liver is the major site of tricaine hydrolysis in mammals and that the selective toxicity of tricaine for poikilotherms is a consequence of their slower rate of hepatic biotransformation of tricaine."}
{"id": "PMID:185357", "title": "Studies on the narcotic receptor in the guinea-pig ileum.", "content": "Studies were conducted on the development and loss of tolerance to morphine in the coaxially stimulated guinea-pig ileum. In ilea from guinea pigs made tolerant to morphine by the procedure of morphine-pellet implantation, the morphine-naloxone pA2 was decreased from 8.5 to 7.6, suggesting a qualitative rather than a quantitative change in the receptors. This change in the pA2 was in the opposite direction from that previously observed with analgesic receptors. Three hours after the administration of a single injection of morphine to the guinea pig, the ileum showed tolerance to morphine, which disappeared by 6 hours. With naloxone as the antagonist, the narcotic analgesics, morphine, methadone, etorphine and levorphanol, yielded higher pA2 values than the narcotic antagonist analgesics, nalorphine, pentazocine and cyclazocine, a result similar to that seen with the analgesic receptors. However, the interaction between naloxone and the narcotic antagonists in the ileum differed from that in the central nervous system when the slopes of the pAx plots were examined. Thus, although the interaction of analgesics with the ileal receptors appears to correlate with the acute effects of the drugs, caution must be exercised to use the ileal receptors as models of analgesic receptors for the study of chronic narcotic effects, i.e., tolerance and dependence.", "contents": "Studies on the narcotic receptor in the guinea-pig ileum. Studies were conducted on the development and loss of tolerance to morphine in the coaxially stimulated guinea-pig ileum. In ilea from guinea pigs made tolerant to morphine by the procedure of morphine-pellet implantation, the morphine-naloxone pA2 was decreased from 8.5 to 7.6, suggesting a qualitative rather than a quantitative change in the receptors. This change in the pA2 was in the opposite direction from that previously observed with analgesic receptors. Three hours after the administration of a single injection of morphine to the guinea pig, the ileum showed tolerance to morphine, which disappeared by 6 hours. With naloxone as the antagonist, the narcotic analgesics, morphine, methadone, etorphine and levorphanol, yielded higher pA2 values than the narcotic antagonist analgesics, nalorphine, pentazocine and cyclazocine, a result similar to that seen with the analgesic receptors. However, the interaction between naloxone and the narcotic antagonists in the ileum differed from that in the central nervous system when the slopes of the pAx plots were examined. Thus, although the interaction of analgesics with the ileal receptors appears to correlate with the acute effects of the drugs, caution must be exercised to use the ileal receptors as models of analgesic receptors for the study of chronic narcotic effects, i.e., tolerance and dependence."}
{"id": "PMID:185358", "title": "The effect of cyclic nucleotides on the release of 3H-dopamine from rat striatal slices.", "content": "Slices (1.0 mm thick and 0.4 cm in diameter) obtained from rat neostriatum were preincubated with 3H-dopamine (3H-DA; 0.8 mugM) for 30 minutes and then superfused at a rate of 1.0 ml/min in glass chambers (volume, 2 ml) for varying lenghts of time prior to  electrical stimulation. Superfusate effluents were continuously collected and analyzed for 3H-DA and 3H-metabolites by liquid scintillation spectrometry after separation by alumina and Dowex 50 column chromatography. 3H-DA represented only a small proportion of the spontaneous overflow of radioactivity (9.8%) but represented the largest portion recovered in the tissue (55%). After electrical stimulation of the slices (biphasic square-wave pulses, 50 pulses/sec; 1.1-msec duration; supramaximal voltage), there was a marked increase in 3H-DA and all 3H-fractions. The percent increase of 3H-DA, 3H-O-methylated + 3H-O-methylated deaminated, 3H-dihydroxyphenylacetic acid and 3H-dihydroxylphenylethanol was 549, 232, 215 AND 246%, respectively. The addition to the superfusion medium of dibutyryl adenosine 3:5-monophosphate (DBcAMP) in the presence or absence of phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, 0.5 mM, or aminophylline, 5 mM) and cyclic adenosine monophosphoric acid in the presence but not the absence of the phosphodiesterase inhibitors potentiated the electrically induced release of 3H-DA. Neither cyclic nucleotide had any effect on the spontaneous overflow of 3H-DA or metabolites, the metabolism of 3H-DA or the uptake of 3H-DA into dopaminergic neurons. Guano sine 3:5-monophosphate was without effect on the electrically induced release of 3H-DA. The ED50 for the DBcAMP potentiation of hte electrically induced release of 3H-DA was 6 mugM. These results extend to the central nervous system the possibility that adenosine 3-5-monophosphate may play a role in the regulation or modulation of monoaminergic synaptic transmission.", "contents": "The effect of cyclic nucleotides on the release of 3H-dopamine from rat striatal slices. Slices (1.0 mm thick and 0.4 cm in diameter) obtained from rat neostriatum were preincubated with 3H-dopamine (3H-DA; 0.8 mugM) for 30 minutes and then superfused at a rate of 1.0 ml/min in glass chambers (volume, 2 ml) for varying lenghts of time prior to  electrical stimulation. Superfusate effluents were continuously collected and analyzed for 3H-DA and 3H-metabolites by liquid scintillation spectrometry after separation by alumina and Dowex 50 column chromatography. 3H-DA represented only a small proportion of the spontaneous overflow of radioactivity (9.8%) but represented the largest portion recovered in the tissue (55%). After electrical stimulation of the slices (biphasic square-wave pulses, 50 pulses/sec; 1.1-msec duration; supramaximal voltage), there was a marked increase in 3H-DA and all 3H-fractions. The percent increase of 3H-DA, 3H-O-methylated + 3H-O-methylated deaminated, 3H-dihydroxyphenylacetic acid and 3H-dihydroxylphenylethanol was 549, 232, 215 AND 246%, respectively. The addition to the superfusion medium of dibutyryl adenosine 3:5-monophosphate (DBcAMP) in the presence or absence of phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, 0.5 mM, or aminophylline, 5 mM) and cyclic adenosine monophosphoric acid in the presence but not the absence of the phosphodiesterase inhibitors potentiated the electrically induced release of 3H-DA. Neither cyclic nucleotide had any effect on the spontaneous overflow of 3H-DA or metabolites, the metabolism of 3H-DA or the uptake of 3H-DA into dopaminergic neurons. Guano sine 3:5-monophosphate was without effect on the electrically induced release of 3H-DA. The ED50 for the DBcAMP potentiation of hte electrically induced release of 3H-DA was 6 mugM. These results extend to the central nervous system the possibility that adenosine 3-5-monophosphate may play a role in the regulation or modulation of monoaminergic synaptic transmission."}
{"id": "PMID:185359", "title": "Adenosine inhibition of isolated rabbit ileum and antagonism by theophylline.", "content": "The spontaneously contracting isolated rabbit ileum was used to study adenosine stimulated receptors. The inhibitory effects of adenosine were not reduced by pretreating the rabbits with either reserpine of 6-hydroxydopamine which were used to eliminate adrenergic function. Similarly the addition of tetrodotoxin to the muscle bath had no effect on the ability of adenosine to produce its inhibitory response. Of the compounds tested for agonistic activity, adenosine and ATP were the most potent (ED50  6 X 10(-7) M). The inhibition by adenosine was antagonized by both theophylline and caffeine in a surmountable manner. Theophylline analogs with charged substituents in position 7 were without antagonist activity. The results suggest that 1) receptors for adenosine or adenine nucleotides are located on the smooth muscle cells of rabbit ileum, 2) receptor stimulation requires and intact adenosine moiety and 3) methylxanthines exert their antagonistic effects by acting as competitive antagonists.", "contents": "Adenosine inhibition of isolated rabbit ileum and antagonism by theophylline. The spontaneously contracting isolated rabbit ileum was used to study adenosine stimulated receptors. The inhibitory effects of adenosine were not reduced by pretreating the rabbits with either reserpine of 6-hydroxydopamine which were used to eliminate adrenergic function. Similarly the addition of tetrodotoxin to the muscle bath had no effect on the ability of adenosine to produce its inhibitory response. Of the compounds tested for agonistic activity, adenosine and ATP were the most potent (ED50  6 X 10(-7) M). The inhibition by adenosine was antagonized by both theophylline and caffeine in a surmountable manner. Theophylline analogs with charged substituents in position 7 were without antagonist activity. The results suggest that 1) receptors for adenosine or adenine nucleotides are located on the smooth muscle cells of rabbit ileum, 2) receptor stimulation requires and intact adenosine moiety and 3) methylxanthines exert their antagonistic effects by acting as competitive antagonists."}
{"id": "PMID:185360", "title": "Destruction of sympathetic nerve terminals by 6-hydroxydopamine: protection by 1-phenyl-3-(2-thiazolyl)-2-thiourea, diethyldithiocarbamate, methimazole, cysteamine, ethanol and n-butanol.", "content": "1-Phenyl-3-(2-thiazolyl)-2-thiourea (PTTU) administered i.p. to mice prevented the neurodegenerative actions of subsequently injected (1 hour later) 6-hydroxydopamine (6-OHDA) or 6-aminodopamine on peripheral adrenergic nerve terminals. Destruction of nerve terminals was studied in vitro in the left atrium by measuring the accumulation of 3H-norepinephrine (3H-HE), and in the iris by both 3H-NE accumulation and fluorescence microscopy methods. Strong protection was observed at 4, 24 and 72 hours after 6-OHDA. The degree of protection was dose-dependent and showed step-wise decrements for concentrations of PTTU below 200 mg/kg (viz., 100, 50 and 20 mg/kg) or concentrations of 6-OHDA-HBr above 7.5 mg/kg (viz., 10, 20 and 50 mg/kg). Protection also fell off at time intervals greater than 1 hour after administration of PTTU (viz., 3 and 5 hours). The appearance (fluorescence microscopy) of the nerve plexus of fully protected mice and the remaining plexus in partially protected mice was essentially normal at 24 hours, except for infrequent large swellings. PTTU proved to be a very effective scavenger of hydroxyl radicals; the formation and scavenging of these radicals was studied by gas chromatography in a system in which the hydroxyl radicals (which were generated during the autoxidation of 6-aminodopamine) gave rise to ethylene, a hydrocarbon gas. Other hydroxyl radical scavengers, namely diethyldithiocarbamate and methimazole, exhibited a protective action on sympathetic nerves in the left atrium; PTTU, diethyldithiocarbamate and methimazole are also recognized as copper chelating compounds. Ethanol, n-butanol and cysteamine, which are well known hydroxyl radical scavengers, also exhibited some degree of protection against 6-OHDA. Blockade of transport of 6-OHDA into sympathetic nerves was ruled out as a protective mechanism by the observation that none of the protective compounds inhibited the accumulation of tritium by the left atrium when 3H-NE was injected in place of 6-OHDA. The mechanism of action for these protective agents has not been definitively established, but scavenging of cytotoxic hydroxyl radicals within neurons may play a significant role.", "contents": "Destruction of sympathetic nerve terminals by 6-hydroxydopamine: protection by 1-phenyl-3-(2-thiazolyl)-2-thiourea, diethyldithiocarbamate, methimazole, cysteamine, ethanol and n-butanol. 1-Phenyl-3-(2-thiazolyl)-2-thiourea (PTTU) administered i.p. to mice prevented the neurodegenerative actions of subsequently injected (1 hour later) 6-hydroxydopamine (6-OHDA) or 6-aminodopamine on peripheral adrenergic nerve terminals. Destruction of nerve terminals was studied in vitro in the left atrium by measuring the accumulation of 3H-norepinephrine (3H-HE), and in the iris by both 3H-NE accumulation and fluorescence microscopy methods. Strong protection was observed at 4, 24 and 72 hours after 6-OHDA. The degree of protection was dose-dependent and showed step-wise decrements for concentrations of PTTU below 200 mg/kg (viz., 100, 50 and 20 mg/kg) or concentrations of 6-OHDA-HBr above 7.5 mg/kg (viz., 10, 20 and 50 mg/kg). Protection also fell off at time intervals greater than 1 hour after administration of PTTU (viz., 3 and 5 hours). The appearance (fluorescence microscopy) of the nerve plexus of fully protected mice and the remaining plexus in partially protected mice was essentially normal at 24 hours, except for infrequent large swellings. PTTU proved to be a very effective scavenger of hydroxyl radicals; the formation and scavenging of these radicals was studied by gas chromatography in a system in which the hydroxyl radicals (which were generated during the autoxidation of 6-aminodopamine) gave rise to ethylene, a hydrocarbon gas. Other hydroxyl radical scavengers, namely diethyldithiocarbamate and methimazole, exhibited a protective action on sympathetic nerves in the left atrium; PTTU, diethyldithiocarbamate and methimazole are also recognized as copper chelating compounds. Ethanol, n-butanol and cysteamine, which are well known hydroxyl radical scavengers, also exhibited some degree of protection against 6-OHDA. Blockade of transport of 6-OHDA into sympathetic nerves was ruled out as a protective mechanism by the observation that none of the protective compounds inhibited the accumulation of tritium by the left atrium when 3H-NE was injected in place of 6-OHDA. The mechanism of action for these protective agents has not been definitively established, but scavenging of cytotoxic hydroxyl radicals within neurons may play a significant role."}
{"id": "PMID:185361", "title": "Effect of Schistosoma mansoni infection on the hepatic drug-metabolizing capacity of mice.", "content": "Since infections with Schistosoma mansoni cause marked histopathological changes in the liver of the host, the effect of this infection on the hepatic drug-metabolizing function was investigated. Severity of Schistosomiasis was determined by worm counts, duration of infection, egg counts and liver weight increases. To overcome difficulties in homogenizing the livers of infected animals, preincubation of the squashed tissues with collagenase and hyaluronidase was used to prepare homogenates. Key component enzyme activities of the hepatic microsomal drug-metabolizing enzyme system (NADPH-cytochrome c reductase and cytochrome P-450) as well as the representative drug-metabolism activities (aminopyrine N-demethylase, aniline hydroxylase, and benzpyrene hydroxylase) were measured for the whole liver and found to be markedly reduced. However, the measurement of microsomal marker enzyme activities (cytochrome b5 and glucose-6-phosphatase) showed significant elevation. To obtain more precise information about the effect of the schistosome infection on the hepatic drug-metabolizing enzyme system, the total activities of microsomal drug-metabolizing enzymes were related to the total microsomal marker enzyme activities in the homogenate.", "contents": "Effect of Schistosoma mansoni infection on the hepatic drug-metabolizing capacity of mice. Since infections with Schistosoma mansoni cause marked histopathological changes in the liver of the host, the effect of this infection on the hepatic drug-metabolizing function was investigated. Severity of Schistosomiasis was determined by worm counts, duration of infection, egg counts and liver weight increases. To overcome difficulties in homogenizing the livers of infected animals, preincubation of the squashed tissues with collagenase and hyaluronidase was used to prepare homogenates. Key component enzyme activities of the hepatic microsomal drug-metabolizing enzyme system (NADPH-cytochrome c reductase and cytochrome P-450) as well as the representative drug-metabolism activities (aminopyrine N-demethylase, aniline hydroxylase, and benzpyrene hydroxylase) were measured for the whole liver and found to be markedly reduced. However, the measurement of microsomal marker enzyme activities (cytochrome b5 and glucose-6-phosphatase) showed significant elevation. To obtain more precise information about the effect of the schistosome infection on the hepatic drug-metabolizing enzyme system, the total activities of microsomal drug-metabolizing enzymes were related to the total microsomal marker enzyme activities in the homogenate."}
{"id": "PMID:185362", "title": "Stimulus-secretion coupling: role of cyclic AMP, cyclic GMP and calcium in mediating enzyme (kallikrein) secretion in the submandibular gland.", "content": "1. The role of adenosine 3':5'-phosphate (cyclic AMP) and guanosine 3':5'-phosphate (cyclic GMP) as second messengers for the enzyme secretory response evoked by the autonomic neurotransmitters, noradrenaline and acetylcholine, is examined in this in vitro study on the guinea-pig submandibular gland. 2. Noradrenaline increased enzyme (kallikrein) secretion. The initial stimulation of enzyme release appeared to be dose-dependent. The time course of cumulative kallikrein secretion revealed a complex pattern. Isoprenaline and phenylephrine were almost as potent as noradrenaline in releasing kallikrein. Both propranolol and phentolamine were required to fully inhibit the noradrenaline-stimulated enzyme secretion. 3. The cumulative secretion of kallikrein evoked by acetylcholine was dose-dependent. The onset of secretion showed a significantly greater time-lag than that observed with noradrenaline. Atropine effectively blocked the release of kallikrein by acetylcholine. 4. Dibutyryl cyclic AMP stimulated enzyme secretion. Dibutyryl cyclic GMP caused an initial increase which was not maintained. 5. The cyclic nucleotide phosphodiesterase inhibitors, theophylline and papaverine, increased basal kallikrein secretion. The action of the cyclic phosphodiesterase inhibitors on the secretory response to noradrenaline, acetylcholine, dibutyryl cyclic AMP and dibutyryl cyclic GMP was complex. In general, the increase in enzyme release produced by the secretagogues was additively enhanced by both inhibitors. 6. Omission of calcium inhibited both acetylcholine and dibutyryl cyclic GMP stimulated kallikrein release, but to a lesser degree than that of noradrenaline and dibutyryl cyclic AMP. High concentrations of extracellular calcium (10 mM) appeared to enhance the action of acetylcholine. 7. Noradrenaline produced a rise in the intracellular level of cyclic AMP. The increase preceded the stimulated secretion of kallikrein. Of the various adrenergic agonists, noradrenaline and isoprenaline were the most potent, whereas phenylephrine was significantly less effective in raising basal cyclic AMP values. Acetylcholine was without effect, even in the presence of a cyclic phosphodiesterase inhibitor. 8. Acetylcholine and noradrenaline raised intracellular levels of cyclic GMP only when the tissue incubations were performed in the presence of a cyclic phosphodiesterase inhibitor. The increase in cyclic GMP produced by acetylcholine preceded enzyme secretion. 9. Morphological data substantiated the finding that the in vitro release of kallikrein evoked by the secretagogues was associated with the depletion of secretory granules and vacuolations in acinar cells of the gland slices. 10. The molecular mechanisms which control enzyme secretion in the exocrine submandibular gland are discussed. Models are presented for the role of transmitter-specific cyclic nucleotides and calcium in stimulus-secretion coupling.", "contents": "Stimulus-secretion coupling: role of cyclic AMP, cyclic GMP and calcium in mediating enzyme (kallikrein) secretion in the submandibular gland. 1. The role of adenosine 3':5'-phosphate (cyclic AMP) and guanosine 3':5'-phosphate (cyclic GMP) as second messengers for the enzyme secretory response evoked by the autonomic neurotransmitters, noradrenaline and acetylcholine, is examined in this in vitro study on the guinea-pig submandibular gland. 2. Noradrenaline increased enzyme (kallikrein) secretion. The initial stimulation of enzyme release appeared to be dose-dependent. The time course of cumulative kallikrein secretion revealed a complex pattern. Isoprenaline and phenylephrine were almost as potent as noradrenaline in releasing kallikrein. Both propranolol and phentolamine were required to fully inhibit the noradrenaline-stimulated enzyme secretion. 3. The cumulative secretion of kallikrein evoked by acetylcholine was dose-dependent. The onset of secretion showed a significantly greater time-lag than that observed with noradrenaline. Atropine effectively blocked the release of kallikrein by acetylcholine. 4. Dibutyryl cyclic AMP stimulated enzyme secretion. Dibutyryl cyclic GMP caused an initial increase which was not maintained. 5. The cyclic nucleotide phosphodiesterase inhibitors, theophylline and papaverine, increased basal kallikrein secretion. The action of the cyclic phosphodiesterase inhibitors on the secretory response to noradrenaline, acetylcholine, dibutyryl cyclic AMP and dibutyryl cyclic GMP was complex. In general, the increase in enzyme release produced by the secretagogues was additively enhanced by both inhibitors. 6. Omission of calcium inhibited both acetylcholine and dibutyryl cyclic GMP stimulated kallikrein release, but to a lesser degree than that of noradrenaline and dibutyryl cyclic AMP. High concentrations of extracellular calcium (10 mM) appeared to enhance the action of acetylcholine. 7. Noradrenaline produced a rise in the intracellular level of cyclic AMP. The increase preceded the stimulated secretion of kallikrein. Of the various adrenergic agonists, noradrenaline and isoprenaline were the most potent, whereas phenylephrine was significantly less effective in raising basal cyclic AMP values. Acetylcholine was without effect, even in the presence of a cyclic phosphodiesterase inhibitor. 8. Acetylcholine and noradrenaline raised intracellular levels of cyclic GMP only when the tissue incubations were performed in the presence of a cyclic phosphodiesterase inhibitor. The increase in cyclic GMP produced by acetylcholine preceded enzyme secretion. 9. Morphological data substantiated the finding that the in vitro release of kallikrein evoked by the secretagogues was associated with the depletion of secretory granules and vacuolations in acinar cells of the gland slices. 10. The molecular mechanisms which control enzyme secretion in the exocrine submandibular gland are discussed. Models are presented for the role of transmitter-specific cyclic nucleotides and calcium in stimulus-secretion coupling."}
{"id": "PMID:185363", "title": "Endogenous prostaglandins, adenosine 3':5'-monophosphate and sodium transport across isolated frog skin.", "content": "1. Sodium transport across isolated frog skin, as measured by the short-circuit current, was decreased by acetylsalicylic acid, mefenamic acid, paracetamol and phenylbutazone. Indomethacin (6 X 10(-6) M) had a biphasic effect on the short-circuit current: a transient increase followed by a sustained decrease. 2. The release of prostaglandin-like material from the skin was reduced by acetylsalicylic acid and indomethacin. Paracetamol caused a significant reduction in the short-circuit current response of the skin to low doses of arachidonic acid, but the response to the highest dose tested was not significantly altered. 3. Indomethacin (6 X 10(-6) M) increased the sensitivity of the skin to applied prostaglandin E1. The other prostaglandin synthetase inhibitors did not have this effect. Indomethacin (6 X 10(-6) M) also enhanced the effect of antidiuretic hormone on the short-circuit current. 4. Indomethacin (30 X 10(-6) M) increased the short-circuit current and diminished the response to applied prostaglandin E1. 5. In sulphate Ringer, theophylline increased the short-circuit current and diminished the response to prostaglandin E1. 6. Prostaglandin E1 increased the levels of cyclic AMP in frog skin and these increases preceded the increases in short-circuit current. There was a seasonal variation in the level of cyclic AMP in the skin: the levels in winter exceeded those in summer. There was also a seasonal variation in the cyclic AMP response to prostaglandin E1: the winter response was greater than that in summer. 7. Indomethacin (6 X 10(-6) M) had a biphasic effect on cyclic AMP levels in the skin, an initial increase followed by a decrease. Indomethacin also potentiated prostaglandin E1 stimulated cyclic AMP accumulation. 8. Theophylline increased cyclic AMP levels in the skin and potentiated prostaglandin E1 stimulated cyclic AMP accumulation. 9. Pre-treatment of the skin with theophylline reversed the effects of cyclic AMP on the short-circuit current and open-circuit potential. 10. It is concluded that endogenous prostaglandins help to maintain sodium transport across isolated frog skin and that the effects of E-type prostaglandins on the short-circuit current are mediated by increased cyclic AMP levels. The transient increase in short-circuit current and the increased skin sensitivity caused by indomethacin (6 X 10(-6) M) are attributed to inhibition of phosphodiesterase activity. The failure of theophylline to potentiate the short-circuit current response of the skin to prostaglandin E1 is attributed to alteration of cyclic AMP action on the skin by theophylline.", "contents": "Endogenous prostaglandins, adenosine 3':5'-monophosphate and sodium transport across isolated frog skin. 1. Sodium transport across isolated frog skin, as measured by the short-circuit current, was decreased by acetylsalicylic acid, mefenamic acid, paracetamol and phenylbutazone. Indomethacin (6 X 10(-6) M) had a biphasic effect on the short-circuit current: a transient increase followed by a sustained decrease. 2. The release of prostaglandin-like material from the skin was reduced by acetylsalicylic acid and indomethacin. Paracetamol caused a significant reduction in the short-circuit current response of the skin to low doses of arachidonic acid, but the response to the highest dose tested was not significantly altered. 3. Indomethacin (6 X 10(-6) M) increased the sensitivity of the skin to applied prostaglandin E1. The other prostaglandin synthetase inhibitors did not have this effect. Indomethacin (6 X 10(-6) M) also enhanced the effect of antidiuretic hormone on the short-circuit current. 4. Indomethacin (30 X 10(-6) M) increased the short-circuit current and diminished the response to applied prostaglandin E1. 5. In sulphate Ringer, theophylline increased the short-circuit current and diminished the response to prostaglandin E1. 6. Prostaglandin E1 increased the levels of cyclic AMP in frog skin and these increases preceded the increases in short-circuit current. There was a seasonal variation in the level of cyclic AMP in the skin: the levels in winter exceeded those in summer. There was also a seasonal variation in the cyclic AMP response to prostaglandin E1: the winter response was greater than that in summer. 7. Indomethacin (6 X 10(-6) M) had a biphasic effect on cyclic AMP levels in the skin, an initial increase followed by a decrease. Indomethacin also potentiated prostaglandin E1 stimulated cyclic AMP accumulation. 8. Theophylline increased cyclic AMP levels in the skin and potentiated prostaglandin E1 stimulated cyclic AMP accumulation. 9. Pre-treatment of the skin with theophylline reversed the effects of cyclic AMP on the short-circuit current and open-circuit potential. 10. It is concluded that endogenous prostaglandins help to maintain sodium transport across isolated frog skin and that the effects of E-type prostaglandins on the short-circuit current are mediated by increased cyclic AMP levels. The transient increase in short-circuit current and the increased skin sensitivity caused by indomethacin (6 X 10(-6) M) are attributed to inhibition of phosphodiesterase activity. The failure of theophylline to potentiate the short-circuit current response of the skin to prostaglandin E1 is attributed to alteration of cyclic AMP action on the skin by theophylline."}
{"id": "PMID:185365", "title": "alpha-Adrenergic, beta-adrenergic and cholinergic mechanisms for amylase secretion by rat parotid gland in vitro.", "content": "1. Rat parotid gland slices, incubated in a balanced, buffered salt solution, were found to be physiologically stable for up to 2 hr with respect to O2 consumption, water content, extracellular space and cation content. 2. The slices could be stimulated to secrete amylase by activation of alpha-adrenergic, beta-adrenergic or muscarinic cholinergic receptors. 3. The secretion elicited through all three receptors appeared to involve exocytosis as revealed by electron microscopy. 4. The beta-agonist, isoprenaline, increased tissue content of cyclic adenosine 3',5'-monophosphate (cyclic AMP); alpha-adrenergic and cholinergic agents had no effect on the level of this cyclic nucleotide. 5. Secretion via cholinergic or alpha-adrenergic mechanisms required extra-cellular calcium; the beta-adrenergic mechanism did not. 6. It was concluded that stimulation of rat parotid cells activates distinctly separate pathways leading ultimately to exocytosis, one pathway involving cyclic AMP, and the other, external Ca2+ ion.", "contents": "alpha-Adrenergic, beta-adrenergic and cholinergic mechanisms for amylase secretion by rat parotid gland in vitro. 1. Rat parotid gland slices, incubated in a balanced, buffered salt solution, were found to be physiologically stable for up to 2 hr with respect to O2 consumption, water content, extracellular space and cation content. 2. The slices could be stimulated to secrete amylase by activation of alpha-adrenergic, beta-adrenergic or muscarinic cholinergic receptors. 3. The secretion elicited through all three receptors appeared to involve exocytosis as revealed by electron microscopy. 4. The beta-agonist, isoprenaline, increased tissue content of cyclic adenosine 3',5'-monophosphate (cyclic AMP); alpha-adrenergic and cholinergic agents had no effect on the level of this cyclic nucleotide. 5. Secretion via cholinergic or alpha-adrenergic mechanisms required extra-cellular calcium; the beta-adrenergic mechanism did not. 6. It was concluded that stimulation of rat parotid cells activates distinctly separate pathways leading ultimately to exocytosis, one pathway involving cyclic AMP, and the other, external Ca2+ ion."}
{"id": "PMID:185366", "title": "An electrophysiological study of the sacral parasympathetic pathway to the colon of the cat.", "content": "1. Electrophysiological techniques were used to study the sacral parasympathetic pathway to the colon of the cat. 2. Electrical stimulation of the sacral ventral roots or the pelvic nerve elicited contractions of the colon and firing in nerve filaments on the serosal surface of the colon. Both responses were markedly reduced by the administration of ganglionic blocking agents. It is concluded that sacral preganglionic fibres to the colon make synaptic contacts with extramural ganglion cells. These cells were identified histologically in small ganglia on the serosal surface of the distal colon and rectum. 3. Transmission in extramural colonic ganglia was cholinergic and mediated by nicotinic receptors. Colonic ganglia did not exhibit large recruiting responses during repetitive (1-4 c/s) preganglionic nerve stimulation or an adrenergic inhibitory mechanism, both of which have been identified in bladder parasympathetic ganglia. It is concluded that colonic ganglia unlike bladder function primarily as simple relay stations and have little potential for modulating the neral activity arising in the central nervus system. 4. The preganglionic input to colonic ganglia was mediated by C fibres with maximal conduction velocities ranging from 0-5 to 1-4 m/sec. Bladder ganglia, on the other hand, received a preganglionic input composed of B fibres with maximal conduction velocities ranging from 8 to 10 m/sec. The possible physiological significance of different types of preganglionic fibres in the sacral outflow is discussed.", "contents": "An electrophysiological study of the sacral parasympathetic pathway to the colon of the cat. 1. Electrophysiological techniques were used to study the sacral parasympathetic pathway to the colon of the cat. 2. Electrical stimulation of the sacral ventral roots or the pelvic nerve elicited contractions of the colon and firing in nerve filaments on the serosal surface of the colon. Both responses were markedly reduced by the administration of ganglionic blocking agents. It is concluded that sacral preganglionic fibres to the colon make synaptic contacts with extramural ganglion cells. These cells were identified histologically in small ganglia on the serosal surface of the distal colon and rectum. 3. Transmission in extramural colonic ganglia was cholinergic and mediated by nicotinic receptors. Colonic ganglia did not exhibit large recruiting responses during repetitive (1-4 c/s) preganglionic nerve stimulation or an adrenergic inhibitory mechanism, both of which have been identified in bladder parasympathetic ganglia. It is concluded that colonic ganglia unlike bladder function primarily as simple relay stations and have little potential for modulating the neral activity arising in the central nervus system. 4. The preganglionic input to colonic ganglia was mediated by C fibres with maximal conduction velocities ranging from 0-5 to 1-4 m/sec. Bladder ganglia, on the other hand, received a preganglionic input composed of B fibres with maximal conduction velocities ranging from 8 to 10 m/sec. The possible physiological significance of different types of preganglionic fibres in the sacral outflow is discussed."}
{"id": "PMID:185368", "title": "Brain stem afferents to the rat medial septum.", "content": "1. Activity of neurones in the medial septal nucleus and the diagonal band was recorded from urethane anaesthesized rats. Responses of the cells to electrical stimulation of the raphe nuclei and nucleus locus coeruleus (LC) were measured. 2. LC stimulation caused a long latency, 30-100 msec, and long duration, 100-300 msec cessation of spontaneous activity of most recorded neurones. When bursting-type neurones were recorded, the stimulation occasionally caused a synchronized repetitive bursting firing pattern. 3. Pre-treatment with drugs which interfere with catecholamine neurotransmission, i.e. reserpine and 6OHDA, prevented the appearance of cellular responses to LC stimulation. 4. Stimulation of the dorsal or the median raphe nuclei generated more complex and less clear-cut responses. These included several types of long (20-50 msec) and short (2-5 msec) latency responses. These responses were also accompanied in some cells by synchronized repetitive bursting. 5. Interference with serotonin neurotransmission with PPCA or reserpine reduced the detection of long latency responses. 6. Short latency responses accompanied by evoked field potentials were recorded also after stimulation of dorsal tegmental nucleus. 7. Rates of spontaneous firing cells were augmented after monoamine neurotransmission interruption whereas after fornix lesion, when there is supposedly an increased monoamine innervation of the septum, cells fire at lower rates than normal. 8. It is suggested that noradrenaline and serotonin may serve as neurotransmitters in the medial-septum-diagonal band areas.", "contents": "Brain stem afferents to the rat medial septum. 1. Activity of neurones in the medial septal nucleus and the diagonal band was recorded from urethane anaesthesized rats. Responses of the cells to electrical stimulation of the raphe nuclei and nucleus locus coeruleus (LC) were measured. 2. LC stimulation caused a long latency, 30-100 msec, and long duration, 100-300 msec cessation of spontaneous activity of most recorded neurones. When bursting-type neurones were recorded, the stimulation occasionally caused a synchronized repetitive bursting firing pattern. 3. Pre-treatment with drugs which interfere with catecholamine neurotransmission, i.e. reserpine and 6OHDA, prevented the appearance of cellular responses to LC stimulation. 4. Stimulation of the dorsal or the median raphe nuclei generated more complex and less clear-cut responses. These included several types of long (20-50 msec) and short (2-5 msec) latency responses. These responses were also accompanied in some cells by synchronized repetitive bursting. 5. Interference with serotonin neurotransmission with PPCA or reserpine reduced the detection of long latency responses. 6. Short latency responses accompanied by evoked field potentials were recorded also after stimulation of dorsal tegmental nucleus. 7. Rates of spontaneous firing cells were augmented after monoamine neurotransmission interruption whereas after fornix lesion, when there is supposedly an increased monoamine innervation of the septum, cells fire at lower rates than normal. 8. It is suggested that noradrenaline and serotonin may serve as neurotransmitters in the medial-septum-diagonal band areas."}
{"id": "PMID:185372", "title": "Folk beliefs of the Chinese and implications to psychiatric nursing.", "content": "Each culture has its own ways of coping with problems. The ancient peoples had developed various devices based on their settings. Those devices are not scientific from the modern man's point of view, however, they have been used over and over through thousands of years. The fact that the world populations have been expanding and growing in tremendous speed, and societies have become more and more complex, people in the world have been confronted with more problems than in the ancient days. Perhaps it is time for the modern man to look back to some of the traditionally used practices in order to draw some implications so that the modern practices can be modified and improved. Through such processes of re-evaluating the traditional practices and modifying modern practices, man will be greatly benefited from the past and the present.", "contents": "Folk beliefs of the Chinese and implications to psychiatric nursing. Each culture has its own ways of coping with problems. The ancient peoples had developed various devices based on their settings. Those devices are not scientific from the modern man's point of view, however, they have been used over and over through thousands of years. The fact that the world populations have been expanding and growing in tremendous speed, and societies have become more and more complex, people in the world have been confronted with more problems than in the ancient days. Perhaps it is time for the modern man to look back to some of the traditionally used practices in order to draw some implications so that the modern practices can be modified and improved. Through such processes of re-evaluating the traditional practices and modifying modern practices, man will be greatly benefited from the past and the present."}
{"id": "PMID:185374", "title": "Preparing students for physical restraint.", "content": "While not encouraging the use of physical restrains on mental patients, the author presents a statement of its continuing use and underscores the need for preparing students for a group of traditional procedures that in some ways are increasingly out of step with our times and aesthetically offensive. Two specific clinical indications for restraint are discussed.", "contents": "Preparing students for physical restraint. While not encouraging the use of physical restrains on mental patients, the author presents a statement of its continuing use and underscores the need for preparing students for a group of traditional procedures that in some ways are increasingly out of step with our times and aesthetically offensive. Two specific clinical indications for restraint are discussed."}
{"id": "PMID:185375", "title": "Nursing care in a combined adolescent medical-psychiatric unit.", "content": "In spite of the problems we have encountered in combining adolescent medical and psychiatric patients, we have found this to be a workable model. In summary, several areas are important in making this model functional: staff interest in both medical and psychiatric patients, in-service programs particularly in psychiatry, and open communication between health care givers. Certainly one of the most positive aspects of this unit is that it provides an environment which allows for easier adjustment to the community after hospitalization. Avoidance of such terms as \"mental hospital,\" \"crazy person\" is less traumatic to the adolescent patient and his family.", "contents": "Nursing care in a combined adolescent medical-psychiatric unit. In spite of the problems we have encountered in combining adolescent medical and psychiatric patients, we have found this to be a workable model. In summary, several areas are important in making this model functional: staff interest in both medical and psychiatric patients, in-service programs particularly in psychiatry, and open communication between health care givers. Certainly one of the most positive aspects of this unit is that it provides an environment which allows for easier adjustment to the community after hospitalization. Avoidance of such terms as \"mental hospital,\" \"crazy person\" is less traumatic to the adolescent patient and his family."}
{"id": "PMID:185377", "title": "Nursing consultation: a clinical specialty.", "content": "In summary, the Mental Health Nurse Consultant is committed to the belief that nursing staff are competent to implement appropriate mental health care. Because of this the consultant utilizes both resource and process consultation to assist staff in determining care plans and to support a realistic method for delivery. The Mental Health Nurse Consultant interviews clients in order to assess dynamics of behavior and uses this information for care plan development. The direct interview also enables the consultant to investigate client perceptions of Psychiatric Mental Health Intervention and support the utilization of direct involvement by a member of the Consultation and Liaison Team. The Mental Health Nurse Consultant acts as a facilitator for ongoing utilization of existing resources through resource and process consultation to members of the Department of Nursing. Thus, consultation as a clinical specialty offers an additional opportunity for nurses to utilize individual skills and refocus the tasks of nursing within the general hospital.", "contents": "Nursing consultation: a clinical specialty. In summary, the Mental Health Nurse Consultant is committed to the belief that nursing staff are competent to implement appropriate mental health care. Because of this the consultant utilizes both resource and process consultation to assist staff in determining care plans and to support a realistic method for delivery. The Mental Health Nurse Consultant interviews clients in order to assess dynamics of behavior and uses this information for care plan development. The direct interview also enables the consultant to investigate client perceptions of Psychiatric Mental Health Intervention and support the utilization of direct involvement by a member of the Consultation and Liaison Team. The Mental Health Nurse Consultant acts as a facilitator for ongoing utilization of existing resources through resource and process consultation to members of the Department of Nursing. Thus, consultation as a clinical specialty offers an additional opportunity for nurses to utilize individual skills and refocus the tasks of nursing within the general hospital."}
{"id": "PMID:185383", "title": "Aspects of gastrointestinal tumors during the reproductive years.", "content": "During the reproductive years, tumors of the digestive organs are uncommon in women in the U.S.A. Nevertheless, two predisposing factors have been identified and are discussed in this article. The first of them concerns the benign and malignant tumors of the liver thought to be associated with the long-term use of oral contraceptives. The second is the increased incidence of colon cancer in patients with longstanding, chronic ulcerative colitis. Measures aimed at prevention and early detection are reviewed and discussed.", "contents": "Aspects of gastrointestinal tumors during the reproductive years. During the reproductive years, tumors of the digestive organs are uncommon in women in the U.S.A. Nevertheless, two predisposing factors have been identified and are discussed in this article. The first of them concerns the benign and malignant tumors of the liver thought to be associated with the long-term use of oral contraceptives. The second is the increased incidence of colon cancer in patients with longstanding, chronic ulcerative colitis. Measures aimed at prevention and early detection are reviewed and discussed."}
{"id": "PMID:185384", "title": "Aberrant serum enzyme patterns in dermatomyositis associated with hepatoma.", "content": "A Caucasian male developed florid dermatomyositis documented by serum enzyme elevation, electromyography, and histology of skin and muscle. Serum enzymes, including creatine phosphokinase (CPK), aldolase, glutamic oxaloacetic transaminase (SGOT), and lactic dehydrogenase (LDH), decreased initially during high dose systemic corticosteroid therapy, although profound muscle weakness persisted. Subsequent elevation of serum LDH and SGOT levels during treatment provided a clue to underlying neoplasia. Primary hepatoma with widespread metastases was found at necropsy.", "contents": "Aberrant serum enzyme patterns in dermatomyositis associated with hepatoma. A Caucasian male developed florid dermatomyositis documented by serum enzyme elevation, electromyography, and histology of skin and muscle. Serum enzymes, including creatine phosphokinase (CPK), aldolase, glutamic oxaloacetic transaminase (SGOT), and lactic dehydrogenase (LDH), decreased initially during high dose systemic corticosteroid therapy, although profound muscle weakness persisted. Subsequent elevation of serum LDH and SGOT levels during treatment provided a clue to underlying neoplasia. Primary hepatoma with widespread metastases was found at necropsy."}
{"id": "PMID:185385", "title": "Bis-basic-substituted polycyclic aromatic compounds. A new class of antiviral agents. 7. Bisalkamine esters of 9-oxoxanthene-2,7-dicarboxylic acid, 3,6-bis-basic ethers of xanthen-9-one, and 2,7-bis(aminoacyl)xanthen-9-ones-xanthenes, and -thioxanthenes.", "content": "3,6-Bis[2-(dimethylamino)ethoxy]-9H-xanthen-9-one dihydrochloride (4, RMI 10874DA) and 1,1'-(9H-xanthene 2,7-diyl)bis[2-(dimethylamino)ethanone] dihydrochloride (16, RMI 11513DA) were found to prolong survival of mice infected with lethal challenges of encephalomyocarditis (EMC) virus. They were effective by oral as well as subcutaneous administration and showed broad-spectrum antiviral activity. They were selected for preclinical evaluation from the five series of compounds named in the title that were synthesized in analogy to tilorone and related fluorenone derivatives, described earlier. In addition to 4 and 16, compounds 11, 12, 17, and 18 showed high antiviral activity on oral as well as subcutaneous administration. High antiviral activity on subcutaneous admistration was found in the bisalkamine esters 1,2, and 14, the bis(aminoacyl)xanthenes 23 and 26, the bis(aminoalkylene)xanthene 31, the bis(aminoacyl)thioxanthenes 34-40, and the bis-basic ethers of 9-benzylide-nexanthenes 41 and 42. Structure-activity relationships showed a decrease of oral activity with increased length of side chains and increased molecular weight of dialkylamino substituents of 3,6-bis-basic ethers of xanthen-9-one and of 2,7-bis(aminoacyl)xanthenes and-xanthen-9-ones. At least one carbonyl or alkenyl function in conjugation to the xanthene nucleus either at the 9 position of the nucleus or in the side chains is required for high antiviral activity.", "contents": "Bis-basic-substituted polycyclic aromatic compounds. A new class of antiviral agents. 7. Bisalkamine esters of 9-oxoxanthene-2,7-dicarboxylic acid, 3,6-bis-basic ethers of xanthen-9-one, and 2,7-bis(aminoacyl)xanthen-9-ones-xanthenes, and -thioxanthenes. 3,6-Bis[2-(dimethylamino)ethoxy]-9H-xanthen-9-one dihydrochloride (4, RMI 10874DA) and 1,1'-(9H-xanthene 2,7-diyl)bis[2-(dimethylamino)ethanone] dihydrochloride (16, RMI 11513DA) were found to prolong survival of mice infected with lethal challenges of encephalomyocarditis (EMC) virus. They were effective by oral as well as subcutaneous administration and showed broad-spectrum antiviral activity. They were selected for preclinical evaluation from the five series of compounds named in the title that were synthesized in analogy to tilorone and related fluorenone derivatives, described earlier. In addition to 4 and 16, compounds 11, 12, 17, and 18 showed high antiviral activity on oral as well as subcutaneous administration. High antiviral activity on subcutaneous admistration was found in the bisalkamine esters 1,2, and 14, the bis(aminoacyl)xanthenes 23 and 26, the bis(aminoalkylene)xanthene 31, the bis(aminoacyl)thioxanthenes 34-40, and the bis-basic ethers of 9-benzylide-nexanthenes 41 and 42. Structure-activity relationships showed a decrease of oral activity with increased length of side chains and increased molecular weight of dialkylamino substituents of 3,6-bis-basic ethers of xanthen-9-one and of 2,7-bis(aminoacyl)xanthenes and-xanthen-9-ones. At least one carbonyl or alkenyl function in conjugation to the xanthene nucleus either at the 9 position of the nucleus or in the side chains is required for high antiviral activity."}
{"id": "PMID:185389", "title": "Potentiation of postjunctional cholinergic sensitivity of rat diaphragm muscle by high-energy-phosphate adenine nucleotides.", "content": "The cholinergic sensitivity of rat diaphragm muscle, me-sured as the magnitude of depolarization responses to repetitive, iontophoretic pulses of acetylcholine (ACh) onto neuromuscular endplates, is increased by addition of ATP to the perfusion medium. Depolarization responses begin to increase within the first min after addition of 10 mM ATP and plateau at 60% above control levels (mean value) after 4 to 6 min. Neither the magnitude nor the time course of the potentiations corresponds to changes in resting potential or membrane resistance. Other nucleotides are equally or less effective at the same concentration: ATP=ADP greater than UTP greater than AMP=GTP (=no added nucleotide control) The duration of the individual ACh responses does not increase during continuous exposure to the active nucleotides for up to 15 min except when the muscle is pretreated with eserine. Mild enzymatic predigestion of the muscle with collagenase and then protease, increasing the availability of the postjunctional membrane to bath-applied drugs, decreases the variability and increases the magnitude of the potentiation to a given dose of ATP. The dose-response curve for ATP is then more than half-maximal at 1 mM and the ranking of the other nucleotides relative to ATP is the same as without predigestion. There is an optimum Ca++ concentration for the potentiation between zero and 2 mM: potentiation is enhanced in Ca++ -free medium, partially blocked in twice-normal Ca++ medium, and totally blocked in Ca++ -free medium 10 min after a 5 min exposure to 2.5 mM EGTA. The similar Ca++ dependence of ACh receptor activation in the absence of added nucleotide suggests that ATP directly facilitates receptor activation by ACh. This facilitory action could be one of the physiological roles for the ATP released from stimulated phrenic nerve.", "contents": "Potentiation of postjunctional cholinergic sensitivity of rat diaphragm muscle by high-energy-phosphate adenine nucleotides. The cholinergic sensitivity of rat diaphragm muscle, me-sured as the magnitude of depolarization responses to repetitive, iontophoretic pulses of acetylcholine (ACh) onto neuromuscular endplates, is increased by addition of ATP to the perfusion medium. Depolarization responses begin to increase within the first min after addition of 10 mM ATP and plateau at 60% above control levels (mean value) after 4 to 6 min. Neither the magnitude nor the time course of the potentiations corresponds to changes in resting potential or membrane resistance. Other nucleotides are equally or less effective at the same concentration: ATP=ADP greater than UTP greater than AMP=GTP (=no added nucleotide control) The duration of the individual ACh responses does not increase during continuous exposure to the active nucleotides for up to 15 min except when the muscle is pretreated with eserine. Mild enzymatic predigestion of the muscle with collagenase and then protease, increasing the availability of the postjunctional membrane to bath-applied drugs, decreases the variability and increases the magnitude of the potentiation to a given dose of ATP. The dose-response curve for ATP is then more than half-maximal at 1 mM and the ranking of the other nucleotides relative to ATP is the same as without predigestion. There is an optimum Ca++ concentration for the potentiation between zero and 2 mM: potentiation is enhanced in Ca++ -free medium, partially blocked in twice-normal Ca++ medium, and totally blocked in Ca++ -free medium 10 min after a 5 min exposure to 2.5 mM EGTA. The similar Ca++ dependence of ACh receptor activation in the absence of added nucleotide suggests that ATP directly facilitates receptor activation by ACh. This facilitory action could be one of the physiological roles for the ATP released from stimulated phrenic nerve."}
{"id": "PMID:185390", "title": "Modulation of postjunctional cholinergic sensitivity of rat diaphragm muscle by cyclic adenosine monophosphate.", "content": "Addition of 2.5 mM cyclic adenosine monophosphate (cAMP) to the solution bathing a rat diaphragm muscle alters the magnitude of depolarization responses to iontophoretic pulses of acetylcholine (ACh) at neuromuscular endplates. Alterations are repeatable with small variability on a given preparation for initial and repeat experiments on both hemidiaphragms, but are different on each preparation. Five min after addition of the nucleotide solution, increases (potentiations) of up to 30% above control levels and decreases (attenuations) to 50% below control levels are observed. The effects on sensitivity to ACh of dibutyryl cAMP (1.25 mM), monobutyryl cAMP (0.25 mM), and cAMP (2.5 mM) in Ca++ -free solution are a function of whether the experiment is an initial one on that preparation or a repeat experiment after 10 or more minutes of perfusion flow. In all three cases, initial exposure attenuates sensitivity (means at 5 min: --30, --10, and --20%, respectively) and repeat exposure potentiates sensitivity (mean: 20% at 5 min, 15% at 5 min, and 10% at 2 min respectively). A concentration of dibutyryl cAMP (0.25 mM) which is without effect on sensitivity alone, produces a large, transient potentiation (mean: 45% at 1 min) in conjunction with 0.5 mM theophylline. A decrease in the rate of desensitization is observed during exposure to 0.25 mM cAMP. The results are interpreted in terms of a physiological mechanism whereby receptor activity at the postjunctional membrane is modulated by cAMP formed from prejunctionally released ATP.", "contents": "Modulation of postjunctional cholinergic sensitivity of rat diaphragm muscle by cyclic adenosine monophosphate. Addition of 2.5 mM cyclic adenosine monophosphate (cAMP) to the solution bathing a rat diaphragm muscle alters the magnitude of depolarization responses to iontophoretic pulses of acetylcholine (ACh) at neuromuscular endplates. Alterations are repeatable with small variability on a given preparation for initial and repeat experiments on both hemidiaphragms, but are different on each preparation. Five min after addition of the nucleotide solution, increases (potentiations) of up to 30% above control levels and decreases (attenuations) to 50% below control levels are observed. The effects on sensitivity to ACh of dibutyryl cAMP (1.25 mM), monobutyryl cAMP (0.25 mM), and cAMP (2.5 mM) in Ca++ -free solution are a function of whether the experiment is an initial one on that preparation or a repeat experiment after 10 or more minutes of perfusion flow. In all three cases, initial exposure attenuates sensitivity (means at 5 min: --30, --10, and --20%, respectively) and repeat exposure potentiates sensitivity (mean: 20% at 5 min, 15% at 5 min, and 10% at 2 min respectively). A concentration of dibutyryl cAMP (0.25 mM) which is without effect on sensitivity alone, produces a large, transient potentiation (mean: 45% at 1 min) in conjunction with 0.5 mM theophylline. A decrease in the rate of desensitization is observed during exposure to 0.25 mM cAMP. The results are interpreted in terms of a physiological mechanism whereby receptor activity at the postjunctional membrane is modulated by cAMP formed from prejunctionally released ATP."}
{"id": "PMID:185392", "title": "Form and distribution of actin and myosin in non-muscle cells: a study using cultured chick embryo fibroblasts.", "content": "Attempting to throw light on the mechanical basis of movement of non-muscle (cf. muscle) cells, the present work aims to determine the form and distribution of actin and myosin in chick embryo fibroblasts. These cells were cultured on formvar, fixed in glutaraldehyde then osmium tetroxide vapours, dehydrated, critical-point dried and examined, in toto, in the electron microscope (EM). Stereoscopic pairs of micrographs were studied to define more exactly the form and distribution of cytoplasmic filaments topographically associated with deformations of the cell surface and with organelle movements through the cytoplasm. Permeating the cytoplasm, interconnecting long and short filaments closely surrounded all organelles, linked with microtubules and polyribosomes and joined to the plasma membrane. These filaments, which varied greatly in width (2-13 nm) were closely associated with large numbers of 'comma-shaped' globoid bodies of approximately 15 nm diameter. Attempting to establish the identity, form and distribution of cytoplasmic myosin, cultured cells were extracted with a cold (4 degrees C) glycerol/pyrophosphate solution for 24 h before being fixed and critical-point dried. EM examination of these cells revealed a residual three-dimensional network of branching and anastomosing 4-13 nm diameter smooth filaments, devoid of fine (2 nm) filaments and globoid bodies. Examination of fixed, critical-point dried, skeletal muscle heavy meromyosin showed globoid structures similar in form and size to the globoid bodies found in cultures fibroblasts. Similarly fixed and critical-point dried paracrystals of actin, polymerized in the presence of Mg2+, appeared as branching interconnecting filaments which, in form and dimensions, resembled the network filaments observed in pyrophosphate-extracted cells. It is concluded that the pyrophosphate-extractable globoid bodies found in cultured fibroblasts represent monomers of myosin, that the broader filaments to which these attach represent actin in Mg2+ paracrystalline form and that the various subcellular movements are brought about by interactions between the two, analogous to those occurring in muscle cells.", "contents": "Form and distribution of actin and myosin in non-muscle cells: a study using cultured chick embryo fibroblasts. Attempting to throw light on the mechanical basis of movement of non-muscle (cf. muscle) cells, the present work aims to determine the form and distribution of actin and myosin in chick embryo fibroblasts. These cells were cultured on formvar, fixed in glutaraldehyde then osmium tetroxide vapours, dehydrated, critical-point dried and examined, in toto, in the electron microscope (EM). Stereoscopic pairs of micrographs were studied to define more exactly the form and distribution of cytoplasmic filaments topographically associated with deformations of the cell surface and with organelle movements through the cytoplasm. Permeating the cytoplasm, interconnecting long and short filaments closely surrounded all organelles, linked with microtubules and polyribosomes and joined to the plasma membrane. These filaments, which varied greatly in width (2-13 nm) were closely associated with large numbers of 'comma-shaped' globoid bodies of approximately 15 nm diameter. Attempting to establish the identity, form and distribution of cytoplasmic myosin, cultured cells were extracted with a cold (4 degrees C) glycerol/pyrophosphate solution for 24 h before being fixed and critical-point dried. EM examination of these cells revealed a residual three-dimensional network of branching and anastomosing 4-13 nm diameter smooth filaments, devoid of fine (2 nm) filaments and globoid bodies. Examination of fixed, critical-point dried, skeletal muscle heavy meromyosin showed globoid structures similar in form and size to the globoid bodies found in cultures fibroblasts. Similarly fixed and critical-point dried paracrystals of actin, polymerized in the presence of Mg2+, appeared as branching interconnecting filaments which, in form and dimensions, resembled the network filaments observed in pyrophosphate-extracted cells. It is concluded that the pyrophosphate-extractable globoid bodies found in cultured fibroblasts represent monomers of myosin, that the broader filaments to which these attach represent actin in Mg2+ paracrystalline form and that the various subcellular movements are brought about by interactions between the two, analogous to those occurring in muscle cells."}
{"id": "PMID:185397", "title": "Evolution of DNA structure: direction, mechanism, rate.", "content": "On the basis of the results of an analysis of frequencies of pyrimidine oligonucleotides, the degree of pyrimidine clustering of DNA in species from different taxa has been determined. A tendency for an increase in the index of clustering of DNA was revealed in the sequence: invertebrates, fishes, amphibians, reptiles, birds, mammals. A mechanism is postulated, according to which the increase in the degree of clustering of DNA d-ring the evolution may be associated with the accumulation of mutations, Purine equalibrium Pyrimidine transversions, resulting in a selective enrichment of one of the chains of DNA with pyrimidines and the other- with purines, i.e. in an increase in the degree of purine-pyrimidine imbalance (asymmetry) of DNA complementary chains. This mechanism of DNA evolution is supported by the presence of positive correlation between the degree of clustering and the degree of the chain asymmetry of natural DNAs, as well as the character of the amino acid substitutions in cytochromes c in different species. The progressive evolution of different groups of organisms on the whole may have been accompanied by an acceleration of the rates of evolution of the DNA structure. On the basis of the amino acid sequence of cytochromes c in different species the degree of clustering and the degree of the chain asymmetry of the corresponding structural genes of DNA was found to have a general tendency towards an increase in the following order: invertebrates, fishes, amphibians, reptiles, birds, mammals. Thus, evolution of cytochrome c cistron is a vector process based on a selection of mutations which, on the one hand, are neurtral to protein, and, on the other hand, result in the sense chain of DNA being enriched with pyrimidines and the nonsense one (and the corresponding mRNA)- with purines. Hence, it is the polynucleotide template rather than protein, that must have been the \"object of selection\". The frequency of substitutions in cytochromes c cistron for vertebrates is 1.56x13(-9) per nucleotide per year. It is believed that the evolutionary modification of the DNA structure may be associated with an increase in the interference resistance of the translation, i.e. with selection for codons of highest readout stability.", "contents": "Evolution of DNA structure: direction, mechanism, rate. On the basis of the results of an analysis of frequencies of pyrimidine oligonucleotides, the degree of pyrimidine clustering of DNA in species from different taxa has been determined. A tendency for an increase in the index of clustering of DNA was revealed in the sequence: invertebrates, fishes, amphibians, reptiles, birds, mammals. A mechanism is postulated, according to which the increase in the degree of clustering of DNA d-ring the evolution may be associated with the accumulation of mutations, Purine equalibrium Pyrimidine transversions, resulting in a selective enrichment of one of the chains of DNA with pyrimidines and the other- with purines, i.e. in an increase in the degree of purine-pyrimidine imbalance (asymmetry) of DNA complementary chains. This mechanism of DNA evolution is supported by the presence of positive correlation between the degree of clustering and the degree of the chain asymmetry of natural DNAs, as well as the character of the amino acid substitutions in cytochromes c in different species. The progressive evolution of different groups of organisms on the whole may have been accompanied by an acceleration of the rates of evolution of the DNA structure. On the basis of the amino acid sequence of cytochromes c in different species the degree of clustering and the degree of the chain asymmetry of the corresponding structural genes of DNA was found to have a general tendency towards an increase in the following order: invertebrates, fishes, amphibians, reptiles, birds, mammals. Thus, evolution of cytochrome c cistron is a vector process based on a selection of mutations which, on the one hand, are neurtral to protein, and, on the other hand, result in the sense chain of DNA being enriched with pyrimidines and the nonsense one (and the corresponding mRNA)- with purines. Hence, it is the polynucleotide template rather than protein, that must have been the \"object of selection\". The frequency of substitutions in cytochromes c cistron for vertebrates is 1.56x13(-9) per nucleotide per year. It is believed that the evolutionary modification of the DNA structure may be associated with an increase in the interference resistance of the translation, i.e. with selection for codons of highest readout stability."}
{"id": "PMID:185398", "title": "Comparative diagnostic aspects of herpes simplex virus tumor-associated antigens.", "content": "Sera from cancer patients and healthy individuals, obtained from two independent sources, were examined for their abilities to react with herpes simplex virus-associated tumor antigens, AG-4 and NVA-TAA (nonvirion antigen-tumor-associated antigen). Both antigens were prepared by infection of HEp-2 cells with herpes simplex virus type 2, and all antigen-antibody interactions were measured by the micro-complement fixation test. Of sera from 16 patients with cancer of the uterine cervix, 81% (P less than 0.01) reacted with NVA-TAA, whereas 78% (P less than 0.001) of 18 sera examined reacted with AG-4. These values differed significantly from those for normal sera, of which 14% reacted with NVA-TAA and 13% with AG-4. Of sera for 8 patients with squamous cell carcinoma of head and neck or vulva, 75% (P less than 0.02) reacted with NVA-TAA, whereas 63% (P less than 0.05) reacted with AG-4. As a group, other cancers (including adenocarcinoma of lung, breast, ovary, and cervix; liposarcoma; sarcoma; melanoma; and carcinoma of the endometrium) did not differ significantly from controls in reactive patterns with AG-4 or NVA-TAA. These studies partly supported the reported preferential reactivity of AG-4 and NVA-TAA with sera of patients with squamous cell carcinoma, especially of the uterine cervix.", "contents": "Comparative diagnostic aspects of herpes simplex virus tumor-associated antigens. Sera from cancer patients and healthy individuals, obtained from two independent sources, were examined for their abilities to react with herpes simplex virus-associated tumor antigens, AG-4 and NVA-TAA (nonvirion antigen-tumor-associated antigen). Both antigens were prepared by infection of HEp-2 cells with herpes simplex virus type 2, and all antigen-antibody interactions were measured by the micro-complement fixation test. Of sera from 16 patients with cancer of the uterine cervix, 81% (P less than 0.01) reacted with NVA-TAA, whereas 78% (P less than 0.001) of 18 sera examined reacted with AG-4. These values differed significantly from those for normal sera, of which 14% reacted with NVA-TAA and 13% with AG-4. Of sera for 8 patients with squamous cell carcinoma of head and neck or vulva, 75% (P less than 0.02) reacted with NVA-TAA, whereas 63% (P less than 0.05) reacted with AG-4. As a group, other cancers (including adenocarcinoma of lung, breast, ovary, and cervix; liposarcoma; sarcoma; melanoma; and carcinoma of the endometrium) did not differ significantly from controls in reactive patterns with AG-4 or NVA-TAA. These studies partly supported the reported preferential reactivity of AG-4 and NVA-TAA with sera of patients with squamous cell carcinoma, especially of the uterine cervix."}
{"id": "PMID:185399", "title": "Pathogenesis of malignant histiocytic lymphoma induced by silica in a colony of specificpathogen-free Wistar rats.", "content": "The occurrence of malignant histiocytic lymphomas (MHLT) after an intrapleural inoculation of silica and the presence of a hyperplastic or granulomatous reaction to the silica were confirmed in cesarean-derived barrier-maintained inbred W rats. A specific hyperplastic reaction in the silica granulomas preceded the appearance of MHLT. Hyperplastic changes were observed when the absolute monocyte count at weeks 25-30 was slightly higher than that seen in the controls. Silica injected intrapleurally penetrated the thymus tissue but the carbon and coal dusts and the silica, which was administered by other routes, did not involve the thymus. Also, silica was the sole dust, when introduced into the coelomic cavities that produced MHLT, which grew rapidly on entering the thymus. Rats that died with MHLT had widespread dissemination with malignant foci situated most consistently above the diaphragm.", "contents": "Pathogenesis of malignant histiocytic lymphoma induced by silica in a colony of specificpathogen-free Wistar rats. The occurrence of malignant histiocytic lymphomas (MHLT) after an intrapleural inoculation of silica and the presence of a hyperplastic or granulomatous reaction to the silica were confirmed in cesarean-derived barrier-maintained inbred W rats. A specific hyperplastic reaction in the silica granulomas preceded the appearance of MHLT. Hyperplastic changes were observed when the absolute monocyte count at weeks 25-30 was slightly higher than that seen in the controls. Silica injected intrapleurally penetrated the thymus tissue but the carbon and coal dusts and the silica, which was administered by other routes, did not involve the thymus. Also, silica was the sole dust, when introduced into the coelomic cavities that produced MHLT, which grew rapidly on entering the thymus. Rats that died with MHLT had widespread dissemination with malignant foci situated most consistently above the diaphragm."}
{"id": "PMID:185400", "title": "Autogenous humoral immunity to baboon xenotropic endogenous type C virus.", "content": "A radioimmune precipitation assay was used to evaluate the humoral immune response of baboons (Papio cynocephalus) to their endogenous, xenotropic, type C (M7) virus. Using 125I or [3H]leucine-labeled intact virus preparation, we demonstrated that baboons possess naturally occurring virus-binding antibodies to this virus. Antibody appeared directed against envelope and not internal viral proteins. Immunoglobulins responsible for virus-binding were predominant in the IgG and IgA serum fractions, whereas IgM participated to a minor degree. The biologic activities of these immunoglobulins were investigated by means of a focus reduction assay for virus neutralization with a murine sarcoma virus (M7) pseudotype. We determined that, despite the presence of considerable virus binding, none of the normal baboon sera tested possessed neutralizing activity for M7 virus.", "contents": "Autogenous humoral immunity to baboon xenotropic endogenous type C virus. A radioimmune precipitation assay was used to evaluate the humoral immune response of baboons (Papio cynocephalus) to their endogenous, xenotropic, type C (M7) virus. Using 125I or [3H]leucine-labeled intact virus preparation, we demonstrated that baboons possess naturally occurring virus-binding antibodies to this virus. Antibody appeared directed against envelope and not internal viral proteins. Immunoglobulins responsible for virus-binding were predominant in the IgG and IgA serum fractions, whereas IgM participated to a minor degree. The biologic activities of these immunoglobulins were investigated by means of a focus reduction assay for virus neutralization with a murine sarcoma virus (M7) pseudotype. We determined that, despite the presence of considerable virus binding, none of the normal baboon sera tested possessed neutralizing activity for M7 virus."}
{"id": "PMID:185401", "title": "Type C virus expression in lymphoma-paralysis-prone wild mice.", "content": "Wild mice trapped near Lake Casitas (LC) in southern California showed a high prevalence of infectious type C virus in the liver, spleen, and thymus within the first few weeks of life. By young adulthood about 80% of LC mice (including their genital tissues) were infected. Virus isolates from these mice cause lymphoma and lower limb paralysis under both natural and experimental conditions. Mice destined to develop paralysis showed higher levels of serum gs antigen early in life, whereas mice destined to develop lymphoma or remain free of these diseases could not be distinguished by this test. The individual variation in virus expression suggested that differences in virus type or in the immune or other host defense mechanisms greatly influenced susceptibility or resistance to indigenous type C virus-caused disease in LC wild mice.", "contents": "Type C virus expression in lymphoma-paralysis-prone wild mice. Wild mice trapped near Lake Casitas (LC) in southern California showed a high prevalence of infectious type C virus in the liver, spleen, and thymus within the first few weeks of life. By young adulthood about 80% of LC mice (including their genital tissues) were infected. Virus isolates from these mice cause lymphoma and lower limb paralysis under both natural and experimental conditions. Mice destined to develop paralysis showed higher levels of serum gs antigen early in life, whereas mice destined to develop lymphoma or remain free of these diseases could not be distinguished by this test. The individual variation in virus expression suggested that differences in virus type or in the immune or other host defense mechanisms greatly influenced susceptibility or resistance to indigenous type C virus-caused disease in LC wild mice."}
{"id": "PMID:185402", "title": "Developmental genetics of neuroblastoma.", "content": "Case reports of neuroblastoma revealed that some individuals are genetically predisposed and that this genetic predisposition may have other consequences. According to a mutation model, two classes of individuals could acquire neuroblastoma. One (prezygotic) was a rare class that carried a dominant gene imparting high risk of the tumor. The other (postzygotic) comprised all other individuals, each at low risk. The model related tumor incidence to germinal and somatic mutation rates and thereby carried implications for environmental modification of tumorigenesis and demographic variation in incidence. Case reports also revealed associations of neuroblastoma with congenital defects and a susceptibility to second tumors. Analogy with retinoblastoma and Wilms' tumor of the kidney suggested that these associations could result from action of a neuroblastoma gene or from chromosomal aberration. One known dominantly inherited condition, von Recklinghausen's disease, could dispose to neuroblastoma and create some associations. According to the two-mutation model, neuroblastoma may have been a single recessive gene disorder at the level of the cell. The phenomena of aganglionosis, neuroblastoma in situ, maturation of neuroblastoma to ganglioneuroma, and spontaneous regression suggested that such a neuroblastoma gene interfered with normal developmental processes. The specificities of this gene and of those for von Recklinghausen's disease and pheochromocytoma suggested that the functiof a membrane macromolecule.", "contents": "Developmental genetics of neuroblastoma. Case reports of neuroblastoma revealed that some individuals are genetically predisposed and that this genetic predisposition may have other consequences. According to a mutation model, two classes of individuals could acquire neuroblastoma. One (prezygotic) was a rare class that carried a dominant gene imparting high risk of the tumor. The other (postzygotic) comprised all other individuals, each at low risk. The model related tumor incidence to germinal and somatic mutation rates and thereby carried implications for environmental modification of tumorigenesis and demographic variation in incidence. Case reports also revealed associations of neuroblastoma with congenital defects and a susceptibility to second tumors. Analogy with retinoblastoma and Wilms' tumor of the kidney suggested that these associations could result from action of a neuroblastoma gene or from chromosomal aberration. One known dominantly inherited condition, von Recklinghausen's disease, could dispose to neuroblastoma and create some associations. According to the two-mutation model, neuroblastoma may have been a single recessive gene disorder at the level of the cell. The phenomena of aganglionosis, neuroblastoma in situ, maturation of neuroblastoma to ganglioneuroma, and spontaneous regression suggested that such a neuroblastoma gene interfered with normal developmental processes. The specificities of this gene and of those for von Recklinghausen's disease and pheochromocytoma suggested that the functiof a membrane macromolecule."}
{"id": "PMID:185403", "title": "Neuroblastoma, Wilms' tumor, and cytomegalovirus.", "content": "The possibility that neuroblastomas and Wilms' tumors are induced by cytomegalovirus (CMV) was raised and discussed. A large percentage of patients with these tumors have complement-fixing antibodies against CMV. A hypothesis was presented.", "contents": "Neuroblastoma, Wilms' tumor, and cytomegalovirus. The possibility that neuroblastomas and Wilms' tumors are induced by cytomegalovirus (CMV) was raised and discussed. A large percentage of patients with these tumors have complement-fixing antibodies against CMV. A hypothesis was presented."}
{"id": "PMID:185404", "title": "A rationale for the treatment of metastatic neuroblastoma.", "content": "In developing a chemotherapeutic program for children with disseminated neuroblastoma, we established three human neuroblastoma lines in cell culture to study the effects of dibutyryl cyclic AMP, papaverine, 5-trifluoromethyl-2'-deoxyuridine, and cyclophosphamide on cell growth, biochemical behavior, and morphology. Based upon our studies, a clinical treatment program was designed. We have treated 15 patients with disseminated neuroblastoma and have established the optimum dose range and sequence of these drugs. Early results were promising; plans for continuation of clinical and experimental studies were discussed.", "contents": "A rationale for the treatment of metastatic neuroblastoma. In developing a chemotherapeutic program for children with disseminated neuroblastoma, we established three human neuroblastoma lines in cell culture to study the effects of dibutyryl cyclic AMP, papaverine, 5-trifluoromethyl-2'-deoxyuridine, and cyclophosphamide on cell growth, biochemical behavior, and morphology. Based upon our studies, a clinical treatment program was designed. We have treated 15 patients with disseminated neuroblastoma and have established the optimum dose range and sequence of these drugs. Early results were promising; plans for continuation of clinical and experimental studies were discussed."}
{"id": "PMID:185408", "title": "Methylation of high-molecular-weight subunit RNA of feline leukemia virus.", "content": "The high-molecular-weight subunit RNA of feline leukemia virus (Rickard strain) (FeLV-R) was analyzed for the presence of methyl groups. After purification of native 50-60S FeLV-R RNA on nondenaturing aqueous sucrose density gradients. FeLV-R 28S subunit RNA, doubly labeled with [14C]uridine and [methyl-3H]methionine, was isolated by centrifugation through denaturing sucrose density gradients in dimethyl sulfoxide. As calculated from their respective 3H/14C ratios. FeLV-R 28S RNA was methylated to the same degree as host cell poly(A)+ mRNA. When the 28S FeLV-R RNA was hydrolyzed to completion with RNase T2 or alkali, all of the methyl-3H chromatographed with mononucleotides on Pellionex-WAX, a weak anion exchanger. The methyl-labeled material co-chromatographed with 6-methyladenosine if the mononucleotide fraction obtained by Pellionex-WAX chromatography was hydrolyzed to nucleosides by bacterial alkaline phosphatase or with 6-methyladenine if purine bases were released from the mononucleotides by acid hydrolysis. In another experiment in which FeLV-R 28S RNA uniformly labeled with 32P was hydrolyzed and then analyzed by Pellionex-WAX chromatography, all of the 32P label again co-chromatographed with mononucleotides. Thus FeLV-R 28S RNA does not appear to contain a 5' structure, either methylated or nonmethylated similar to those recently reported for cellular and some animal virus mRNA's.", "contents": "Methylation of high-molecular-weight subunit RNA of feline leukemia virus. The high-molecular-weight subunit RNA of feline leukemia virus (Rickard strain) (FeLV-R) was analyzed for the presence of methyl groups. After purification of native 50-60S FeLV-R RNA on nondenaturing aqueous sucrose density gradients. FeLV-R 28S subunit RNA, doubly labeled with [14C]uridine and [methyl-3H]methionine, was isolated by centrifugation through denaturing sucrose density gradients in dimethyl sulfoxide. As calculated from their respective 3H/14C ratios. FeLV-R 28S RNA was methylated to the same degree as host cell poly(A)+ mRNA. When the 28S FeLV-R RNA was hydrolyzed to completion with RNase T2 or alkali, all of the methyl-3H chromatographed with mononucleotides on Pellionex-WAX, a weak anion exchanger. The methyl-labeled material co-chromatographed with 6-methyladenosine if the mononucleotide fraction obtained by Pellionex-WAX chromatography was hydrolyzed to nucleosides by bacterial alkaline phosphatase or with 6-methyladenine if purine bases were released from the mononucleotides by acid hydrolysis. In another experiment in which FeLV-R 28S RNA uniformly labeled with 32P was hydrolyzed and then analyzed by Pellionex-WAX chromatography, all of the 32P label again co-chromatographed with mononucleotides. Thus FeLV-R 28S RNA does not appear to contain a 5' structure, either methylated or nonmethylated similar to those recently reported for cellular and some animal virus mRNA's."}
{"id": "PMID:185409", "title": "Polyoma genome in hamster BHK-21-C13 cells: integration into cellular DNA and induction of the viral replication.", "content": "When grown at 39.5 degrees C, BHK-21 C-13 cells transformed by A gene mutants of polyoma virus contain viral sequences that are predominantly associated with cellular DNA pelleted in the Hirt lysis procedure. At this temperature, in cells that are inducible for viral DNA replication (Folk, 1973), the majority of the viral genomes are covalently joined with cellular DNA's containing repetitious sequences. Upon a shift to 31 degrees C, free viral genomes appear and are replicated. Coupled with the replication of the free viral genomes at 31 degrees C is an increase in the viral genomes associated with cellular DNA.", "contents": "Polyoma genome in hamster BHK-21-C13 cells: integration into cellular DNA and induction of the viral replication. When grown at 39.5 degrees C, BHK-21 C-13 cells transformed by A gene mutants of polyoma virus contain viral sequences that are predominantly associated with cellular DNA pelleted in the Hirt lysis procedure. At this temperature, in cells that are inducible for viral DNA replication (Folk, 1973), the majority of the viral genomes are covalently joined with cellular DNA's containing repetitious sequences. Upon a shift to 31 degrees C, free viral genomes appear and are replicated. Coupled with the replication of the free viral genomes at 31 degrees C is an increase in the viral genomes associated with cellular DNA."}
{"id": "PMID:185410", "title": "Synthesis of RNA by mutants of vesicular stomatitis virus (Indiana serotype) and the ability of wild-type VSV New Jersey to complement the VSV Indiana ts G I-114 transcription defect.", "content": "The ability of certain vesicular stomatitis virus (VSV; Indiana serotype) temperature-sensitive (ts) mutants to synthesize intracellular viral complementary RNA (vcRNA) at permissive or nonpermissive temperatures for productive infections has been investigated. Mutants belonging to complementation groups II, III, and V synthesize RNA at nonpermissive temperature in amounts essentially equivalent to that obtained at permissive temperatures. Mutant ts G I-114 possesses a thermolabile transcriptase and does not synthesize vcRNA at 40 degrees C; however, mutants ts O I-5, O I-53, O I-78, and O I-80 possess thermostabile transcriptases that are capable of some vcRNA synthesis at 40 degrees C. All five group I mutants are defective in their secondary transcription ability at 40 degrees C. Wild-type VSV New Jersey virus is able to complement the transcription defect of ts G I-114 at 40 degrees C. This complementation is inhibited by puromycin, suggesting that a viral gene product of VSV New Jersey (e.g., its transcriptase or a transcriptase component) is involved. Mokola virus is not able to complement the ts G I-114 defect, although Mokola does synthesize vcRNA in infected cells (in  the presence or absence of cycloheximide).", "contents": "Synthesis of RNA by mutants of vesicular stomatitis virus (Indiana serotype) and the ability of wild-type VSV New Jersey to complement the VSV Indiana ts G I-114 transcription defect. The ability of certain vesicular stomatitis virus (VSV; Indiana serotype) temperature-sensitive (ts) mutants to synthesize intracellular viral complementary RNA (vcRNA) at permissive or nonpermissive temperatures for productive infections has been investigated. Mutants belonging to complementation groups II, III, and V synthesize RNA at nonpermissive temperature in amounts essentially equivalent to that obtained at permissive temperatures. Mutant ts G I-114 possesses a thermolabile transcriptase and does not synthesize vcRNA at 40 degrees C; however, mutants ts O I-5, O I-53, O I-78, and O I-80 possess thermostabile transcriptases that are capable of some vcRNA synthesis at 40 degrees C. All five group I mutants are defective in their secondary transcription ability at 40 degrees C. Wild-type VSV New Jersey virus is able to complement the transcription defect of ts G I-114 at 40 degrees C. This complementation is inhibited by puromycin, suggesting that a viral gene product of VSV New Jersey (e.g., its transcriptase or a transcriptase component) is involved. Mokola virus is not able to complement the ts G I-114 defect, although Mokola does synthesize vcRNA in infected cells (in  the presence or absence of cycloheximide)."}
{"id": "PMID:185411", "title": "Polyadenylate sequences of human rhinovirus and poliovirus RNA and cordycepin sensitivity of virus replication.", "content": "The polyadenylate [poly(A)] content of the genome RNA of human rhinovirus type 14 (HRV-14) is nearly twice as large as that of the genome RNA of poliovirus type 2. The poly(A) content of viral RNA was determined to be the RNase-resistant fraction of 32P-labeled viral RNA extracted from purified virions. Polyacrylamide gel electrophoresis indicated that the poly(A) sequences of HRV-14 are more heterogenous and on an average larger than those of poliovirus RNA. On the basis of susceptibility to micrococcal polynucleotide phosphorylase the rhinovirus genome terminates in poly(A). Replication of both viruses is almost totally inhibited by cordycepin at 50 mug/ml. At lower concentrations, rhinovirus replication is more sensitive to cordycepin than poliovirus replication. Addition of cordycepin (75 mug/ml) to infected culture prior to or during viral RNA replication results in more or less complete inhibition of virus-specific RNA synthesis. The results do not indicate that cordycepin sensitivity of either virus is due to preferential inhibition of viral poly(A) synthesis by this antibiotic.", "contents": "Polyadenylate sequences of human rhinovirus and poliovirus RNA and cordycepin sensitivity of virus replication. The polyadenylate [poly(A)] content of the genome RNA of human rhinovirus type 14 (HRV-14) is nearly twice as large as that of the genome RNA of poliovirus type 2. The poly(A) content of viral RNA was determined to be the RNase-resistant fraction of 32P-labeled viral RNA extracted from purified virions. Polyacrylamide gel electrophoresis indicated that the poly(A) sequences of HRV-14 are more heterogenous and on an average larger than those of poliovirus RNA. On the basis of susceptibility to micrococcal polynucleotide phosphorylase the rhinovirus genome terminates in poly(A). Replication of both viruses is almost totally inhibited by cordycepin at 50 mug/ml. At lower concentrations, rhinovirus replication is more sensitive to cordycepin than poliovirus replication. Addition of cordycepin (75 mug/ml) to infected culture prior to or during viral RNA replication results in more or less complete inhibition of virus-specific RNA synthesis. The results do not indicate that cordycepin sensitivity of either virus is due to preferential inhibition of viral poly(A) synthesis by this antibiotic."}
{"id": "PMID:185412", "title": "Sequence arrangement in herpes simplex virus type 1 DNA: identification of terminal fragments in restriction endonuclease digests and evidence for inversions in redundant and unique sequences.", "content": "It has been proposed by Sheldrick and Berthelot (1974) that the terminal sequences of herpes simplex virus type 1 (HSV-1) DNA are repeated in an internal inverted form and that the inverted redundant sequences delimit and separate two unique sequences, S and L. In this study the sequence arrangement in HSV-1 DNA has been investigated with restriction endonuclease cleavage, end-labeling studies, and molecular hybridization experiments. The terminal fragments in digests with restriction endonucleases Hind III, Hpa-1, EcoRI and Bum were identified and shown to be consistent with the Sheldrick and Berthelot model. Inverted fragments which contain unique sequences as well as redundant sequences, and which the model predicts, were identified by DNA-DNA hybridization studies. Further cleavage of Bum fragments with Hpa-1 also revealed inversions of the terminal sequences that contained unique sequences. The results obtained showed that the unique sequences S and L are relatively inverted in different DNA molecules in the population, resulting in the presence of four related genomes with rearranged sequences in apparently equal amounts. The redundant sequences bounding S do not share complete sequence homology with those bounding L, but hybridization studies are presented which show that the terminal 0.3% of the genome is repeated in every redundant sequence.", "contents": "Sequence arrangement in herpes simplex virus type 1 DNA: identification of terminal fragments in restriction endonuclease digests and evidence for inversions in redundant and unique sequences. It has been proposed by Sheldrick and Berthelot (1974) that the terminal sequences of herpes simplex virus type 1 (HSV-1) DNA are repeated in an internal inverted form and that the inverted redundant sequences delimit and separate two unique sequences, S and L. In this study the sequence arrangement in HSV-1 DNA has been investigated with restriction endonuclease cleavage, end-labeling studies, and molecular hybridization experiments. The terminal fragments in digests with restriction endonucleases Hind III, Hpa-1, EcoRI and Bum were identified and shown to be consistent with the Sheldrick and Berthelot model. Inverted fragments which contain unique sequences as well as redundant sequences, and which the model predicts, were identified by DNA-DNA hybridization studies. Further cleavage of Bum fragments with Hpa-1 also revealed inversions of the terminal sequences that contained unique sequences. The results obtained showed that the unique sequences S and L are relatively inverted in different DNA molecules in the population, resulting in the presence of four related genomes with rearranged sequences in apparently equal amounts. The redundant sequences bounding S do not share complete sequence homology with those bounding L, but hybridization studies are presented which show that the terminal 0.3% of the genome is repeated in every redundant sequence."}
{"id": "PMID:185413", "title": "Physical maps for Herpes simplex virus type 1 DNA for restriction endonucleases Hind III, Hpa-1, and X. bad.", "content": "It has been proposed that the genome of herpes simplex virus type 1 (HSV-1) consists of two internal unique sequences, S and L, bounded by two sets of redundant sequences (P. Sheldrick and N. Berthelot, 1974). In this arrangement, terminal sequences (TRs and TRl) are repeated in an internal inverted form (IRs and IRl) and delimit S and L. Furthermore, a body of evidence has accumulated that suggests that S and L themselves are inverted, giving rise to four related forms of the HSV genome. In this study the ordering of restruction endonuclease fragments of HSV-1 DNA for physical maps has been studied using molecular hybridization techniques and the cleavage of isolated restriction endonuclease fragments with further restriction endonucleases. Physical maps for the fragments produced by Hind III, Hpa-1, and X. bad have been constructed for the four related forms of the HSV-1 genome. TRs and IRs were found to be between 3.5 x 10(6) and 4.5 x 10(6) daltons, TRl and IRl about 6 x 10(6) daltons, S about 8 x 10(6) to 9 x 10(6) daltons, and L about 6.8 x 10(6) daltons.", "contents": "Physical maps for Herpes simplex virus type 1 DNA for restriction endonucleases Hind III, Hpa-1, and X. bad. It has been proposed that the genome of herpes simplex virus type 1 (HSV-1) consists of two internal unique sequences, S and L, bounded by two sets of redundant sequences (P. Sheldrick and N. Berthelot, 1974). In this arrangement, terminal sequences (TRs and TRl) are repeated in an internal inverted form (IRs and IRl) and delimit S and L. Furthermore, a body of evidence has accumulated that suggests that S and L themselves are inverted, giving rise to four related forms of the HSV genome. In this study the ordering of restruction endonuclease fragments of HSV-1 DNA for physical maps has been studied using molecular hybridization techniques and the cleavage of isolated restriction endonuclease fragments with further restriction endonucleases. Physical maps for the fragments produced by Hind III, Hpa-1, and X. bad have been constructed for the four related forms of the HSV-1 genome. TRs and IRs were found to be between 3.5 x 10(6) and 4.5 x 10(6) daltons, TRl and IRl about 6 x 10(6) daltons, S about 8 x 10(6) to 9 x 10(6) daltons, and L about 6.8 x 10(6) daltons."}
{"id": "PMID:185414", "title": "Generation of defective virus after infection of newborn rats with reovirus.", "content": "When 2-day-old rats were inoculated subcutaneously with the R2 strain of reovirus type 3 or with a class B (352) or class C (447) temperature-sensitive (ts) mutant, 5 to 10% of the animals died from acute encephalitis within 12 days. Approximately half of the survivors recovered rapidly and grew normally, but the remainder became runted. Two phases of infection are distinguished in the animals: an acute phase during which infectious virus reaches a maximum titer in brain and other tissues by 10 days p.i. and thes runting of the rats and the slow disappearance of virus from their brains over a period of 2 months or so. Virus isolated from chronically infected brains generally retained the genetic character (ts or wild type) of the inoculated virus, but two exceptions to this are described. Defective virions lacking the L1 segment of the viral genome (L1 defectives) were generated in rat brains during the acute phase of infection. Defective virus was also generated during the chronic phase, but during this period defectives were found with multiple segments deleted from the genome in addition to L1 defectives. In another type of experiment defective virus exerted a marked protective effect when inoculated intracerebrally with R2 virus. In the absence of defectives all animals died, but in their presence 17 of 23 animals survived and 15 of 23 became runted and chronically infected. The formation and evolution of defective particles in the brains of these rats were similar to those found in rats chronically infected after subcutaneous inoculation of reovirus. We conclude that the formation of defective virus particles may play a role in the initiation and maintenance of chronic neutropic infections with reovirus.", "contents": "Generation of defective virus after infection of newborn rats with reovirus. When 2-day-old rats were inoculated subcutaneously with the R2 strain of reovirus type 3 or with a class B (352) or class C (447) temperature-sensitive (ts) mutant, 5 to 10% of the animals died from acute encephalitis within 12 days. Approximately half of the survivors recovered rapidly and grew normally, but the remainder became runted. Two phases of infection are distinguished in the animals: an acute phase during which infectious virus reaches a maximum titer in brain and other tissues by 10 days p.i. and thes runting of the rats and the slow disappearance of virus from their brains over a period of 2 months or so. Virus isolated from chronically infected brains generally retained the genetic character (ts or wild type) of the inoculated virus, but two exceptions to this are described. Defective virions lacking the L1 segment of the viral genome (L1 defectives) were generated in rat brains during the acute phase of infection. Defective virus was also generated during the chronic phase, but during this period defectives were found with multiple segments deleted from the genome in addition to L1 defectives. In another type of experiment defective virus exerted a marked protective effect when inoculated intracerebrally with R2 virus. In the absence of defectives all animals died, but in their presence 17 of 23 animals survived and 15 of 23 became runted and chronically infected. The formation and evolution of defective particles in the brains of these rats were similar to those found in rats chronically infected after subcutaneous inoculation of reovirus. We conclude that the formation of defective virus particles may play a role in the initiation and maintenance of chronic neutropic infections with reovirus."}
{"id": "PMID:185415", "title": "5'-terminus of Moloney murine leukemia virus 35s RNA is m7G5' ppp5' GmpCp.", "content": "The 5'-terminal sequence m(7)G(5') ppp(5') GmpCp was isolated from Moloney murine leukemia virus 35S RNA after digestion of (32)P-labeled RNA with RNases T1, T2, and A followed by pH 3.5 ionophoresis on DEAE paper.", "contents": "5'-terminus of Moloney murine leukemia virus 35s RNA is m7G5' ppp5' GmpCp. The 5'-terminal sequence m(7)G(5') ppp(5') GmpCp was isolated from Moloney murine leukemia virus 35S RNA after digestion of (32)P-labeled RNA with RNases T1, T2, and A followed by pH 3.5 ionophoresis on DEAE paper."}
{"id": "PMID:185416", "title": "RNA complementary to the genome of RNA tumor viruses in virions and virus-producing cells.", "content": "Cells producing type C (avain sarcoma virus) or type B (mouse mammary tumor virus) RNA tumor viruses contain small amounts of RNA complementary to the viral genomes. The negative strands are complementary to at least 30 to 45% of the viral genomes and are found as RNA-RNA duplexes in the nucleus and cytoplasm of infected cells and in mature virions.", "contents": "RNA complementary to the genome of RNA tumor viruses in virions and virus-producing cells. Cells producing type C (avain sarcoma virus) or type B (mouse mammary tumor virus) RNA tumor viruses contain small amounts of RNA complementary to the viral genomes. The negative strands are complementary to at least 30 to 45% of the viral genomes and are found as RNA-RNA duplexes in the nucleus and cytoplasm of infected cells and in mature virions."}
{"id": "PMID:185417", "title": "Simian virus 40 mutants carrying two temperature-sensitive mutations.", "content": "Five temperature-sensitive mutants of simian virus 40 containing two temperature-sensitive mutations were isolated. The double mutant of the A and D complementation groups, like the D mutants, failed to complement by conventional complementation analysis and did not induce host DNA synthesis at 40 degrees C. However, under conditions that suppressed the D defect, the A:D double mutant expressed only the A defect. Thus, viral DNA replication dropped rapidly after this mutant was shifted from permissive to restrictive temperatures. The A:D double mutant failed to transfrom at the restrictive temperature when subconfluent Chinese hamster lung monolayers were used. Double mutants of A:B, A:C, and A:BC complementation groups, like their A parent, were defective in viral DNA replication, in the induction of host DNA synthesis and in the transformation of secondary Chinese hamster lung cells at the nonpermissive temperature.", "contents": "Simian virus 40 mutants carrying two temperature-sensitive mutations. Five temperature-sensitive mutants of simian virus 40 containing two temperature-sensitive mutations were isolated. The double mutant of the A and D complementation groups, like the D mutants, failed to complement by conventional complementation analysis and did not induce host DNA synthesis at 40 degrees C. However, under conditions that suppressed the D defect, the A:D double mutant expressed only the A defect. Thus, viral DNA replication dropped rapidly after this mutant was shifted from permissive to restrictive temperatures. The A:D double mutant failed to transfrom at the restrictive temperature when subconfluent Chinese hamster lung monolayers were used. Double mutants of A:B, A:C, and A:BC complementation groups, like their A parent, were defective in viral DNA replication, in the induction of host DNA synthesis and in the transformation of secondary Chinese hamster lung cells at the nonpermissive temperature."}
{"id": "PMID:185418", "title": "Consequences of herpes simplex virus type 2 and human cell interaction at supraoptimal temperatures.", "content": "The consequences of herpes simplex virus type 2 (HSV-2) and human embryonic fibroblast cell interaction at different temperatures (37, 40, and 42 degrees C) were investigated. Incubation at 37 or 40 degrees C was permissive for HSV-2 inhibition of host DNA synthesis, induction of virus-specific DNA replication, and infectious virus production. The amount of [methyl-3H]thymidine incorporated into viral DNA and the final yield of new infectious virus were significantly reduced at 40 degrees C compared to 37 degrees C. At 42 degrees C, detectable virus-specific DNA synthesis was totally blocked. Maximum stimulation of host cell DNA synthesis at 42 degrees C was measured after a multiplicity of infection of 0.5 to 1.0 PFU/cell. By autoradiography, data indicated that HSV-2 stimulates host cell chromosomal DNA synthesis. Stimulation of thymidine kinase activity with thermostability properties in common with a virus enzyme was detected during the first 24 h of infection at 42 degrees C, after 24 h the enhanced thymidine kinase activity had properties in common with host cell isozymes. The data obtained during this investigation indicated that stimulation of host cell DNA synthesis does not require viral DNA synthesis.", "contents": "Consequences of herpes simplex virus type 2 and human cell interaction at supraoptimal temperatures. The consequences of herpes simplex virus type 2 (HSV-2) and human embryonic fibroblast cell interaction at different temperatures (37, 40, and 42 degrees C) were investigated. Incubation at 37 or 40 degrees C was permissive for HSV-2 inhibition of host DNA synthesis, induction of virus-specific DNA replication, and infectious virus production. The amount of [methyl-3H]thymidine incorporated into viral DNA and the final yield of new infectious virus were significantly reduced at 40 degrees C compared to 37 degrees C. At 42 degrees C, detectable virus-specific DNA synthesis was totally blocked. Maximum stimulation of host cell DNA synthesis at 42 degrees C was measured after a multiplicity of infection of 0.5 to 1.0 PFU/cell. By autoradiography, data indicated that HSV-2 stimulates host cell chromosomal DNA synthesis. Stimulation of thymidine kinase activity with thermostability properties in common with a virus enzyme was detected during the first 24 h of infection at 42 degrees C, after 24 h the enhanced thymidine kinase activity had properties in common with host cell isozymes. The data obtained during this investigation indicated that stimulation of host cell DNA synthesis does not require viral DNA synthesis."}
{"id": "PMID:185419", "title": "Simian virus 40 DNA replication in nuclear monolayers.", "content": "Simian virus 40 DNA replication has been studied in nuclear monolayers prepared by treatment of monolayers of BSC-1 monkey kidney cells with Nonidet P-40. These nuclear monolayers incorporated [3H]TTP into two types of viral replicative intermediates that sediment as 25-26S and 22-23S species, respectively, in neutral sucrose gradients. The 22-23S species behaves, in dye buoyant density equilibrium gradients, as a late replicative intermediate. Examination of both species in alkaline sucrose gradients revealed the presence of two types of newly synthesized strands: (i) 4-7S strands and (ii) full-length, or nearly full-length, 10-16S strands. At low TTP concentrations (less than 0.5 muM), the two size classes were found in approximately equal amounts. However, at 10 to 50 muM TTP, the proportion of the longer strands increased, with a corresponding decrease in the relative amount of the 4-7S species. Thus, the joining of small, Okazaki-like fragments to the growing chain appears to require a much higher concentration of TTP than the synthesis of the fragments themselves. Replicating simian virus 40 DNA synthesized in the nuclear monolayers is is associated with \"M bands\", as previously demonstrated for replicating simian virus 40 DNA in cultured whole cells.", "contents": "Simian virus 40 DNA replication in nuclear monolayers. Simian virus 40 DNA replication has been studied in nuclear monolayers prepared by treatment of monolayers of BSC-1 monkey kidney cells with Nonidet P-40. These nuclear monolayers incorporated [3H]TTP into two types of viral replicative intermediates that sediment as 25-26S and 22-23S species, respectively, in neutral sucrose gradients. The 22-23S species behaves, in dye buoyant density equilibrium gradients, as a late replicative intermediate. Examination of both species in alkaline sucrose gradients revealed the presence of two types of newly synthesized strands: (i) 4-7S strands and (ii) full-length, or nearly full-length, 10-16S strands. At low TTP concentrations (less than 0.5 muM), the two size classes were found in approximately equal amounts. However, at 10 to 50 muM TTP, the proportion of the longer strands increased, with a corresponding decrease in the relative amount of the 4-7S species. Thus, the joining of small, Okazaki-like fragments to the growing chain appears to require a much higher concentration of TTP than the synthesis of the fragments themselves. Replicating simian virus 40 DNA synthesized in the nuclear monolayers is is associated with \"M bands\", as previously demonstrated for replicating simian virus 40 DNA in cultured whole cells."}
{"id": "PMID:185420", "title": "Isolation and structural characterization of monomeric and dimeric forms of replicative intermediates of Kilham rat virus DNA.", "content": "Two virus-specific species of newly synthesized DNA were isolated from rat fibroblast cell cultures infected with the Kilham rat virus (RV). These two DNA species were purified; their behavior on hydroxyapatite chromatography and their sedimentation coefficients in sucrose gradients were determined. One of the two species corresponds to the linear double-stranded form of the RV DNA, and the other corresponds to the dimeric duplex form. After denaturation, a fraction of both species showed an intramolecular renaturation; these molecules are composed of viral strand covalently linked to complementary strand. Models for the structure of both species are posposed. Both species may be considered as double-strand replicative intermediates of the single-stranded RV DNA.", "contents": "Isolation and structural characterization of monomeric and dimeric forms of replicative intermediates of Kilham rat virus DNA. Two virus-specific species of newly synthesized DNA were isolated from rat fibroblast cell cultures infected with the Kilham rat virus (RV). These two DNA species were purified; their behavior on hydroxyapatite chromatography and their sedimentation coefficients in sucrose gradients were determined. One of the two species corresponds to the linear double-stranded form of the RV DNA, and the other corresponds to the dimeric duplex form. After denaturation, a fraction of both species showed an intramolecular renaturation; these molecules are composed of viral strand covalently linked to complementary strand. Models for the structure of both species are posposed. Both species may be considered as double-strand replicative intermediates of the single-stranded RV DNA."}
{"id": "PMID:185421", "title": "Origin of polyoma virus-associated endonuclease.", "content": "Polyoma virus particles purified from infected cells, but not from the culture medium, exhibited an endonuclease activity distinct from the serum contaminant recently described. This endonuclease cleaved form I polyoma DNA once only per molecule, at one of three possible sites corresponding to the known adenosine-ribosylthymine-rich regions of the molecule.", "contents": "Origin of polyoma virus-associated endonuclease. Polyoma virus particles purified from infected cells, but not from the culture medium, exhibited an endonuclease activity distinct from the serum contaminant recently described. This endonuclease cleaved form I polyoma DNA once only per molecule, at one of three possible sites corresponding to the known adenosine-ribosylthymine-rich regions of the molecule."}
{"id": "PMID:185422", "title": "Analysis of intracellular feline leukemia virus proteins. I. Identification of a 60,000-dalton precursor of feline leukemia virus p30.", "content": "The synthesis and release of feline leukemia virus p30 was studied using a permanently infected feline thymus tumor cell line. Disrupted cells were divided into two subcellular fractions, a cytoplasmic extract (CE) representing cellular material soluble in 0.5% NP-40 and a particulate fraction (PF) insoluble in 0.5% NP-40 but soluble in 0.2% deoxycholate and 0.5% NP-40. Intracellular feline leukemia virus p30 was isolated from infected cells by immune precipitation with antiserum to p30 and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the precipitated proteins. Cells labeled for 3 h with [35S]methionine contained equal amounts of p30 in both the CE and the PF. p30 synthesis was estimated to be 0.8% of the total host cell protein synthesis. Immune precipitates from cell pulse labeled for 2.5 min contained a labeled 60,000-dalton polypeptide (Pp60) in the PF and a polypeptide in the CE that comigrated with feline leukemia virus p30 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When cells were chased after a pulse label, there was a rapid loss of Pp60 in the PF and an accumulation of p30 in the CE within 30 min followed by distribution of p30 in both the PF and the CE. Estimation of intracellular and extracellular p30 levels during a 0.5- to 24-h chase period suggested that most of the newly synthesized p30 was incorporated into extracellular virus. Typtic peptide analysis of labeled Pp60 and p30 demonstrated the presence of 13 of 15 p30 peptides within the Pp60 molecule. The tryptic peptide analysis in concert with the pulse-chase labeling data provides strong evidence that Pp60 is a precursor of p30.", "contents": "Analysis of intracellular feline leukemia virus proteins. I. Identification of a 60,000-dalton precursor of feline leukemia virus p30. The synthesis and release of feline leukemia virus p30 was studied using a permanently infected feline thymus tumor cell line. Disrupted cells were divided into two subcellular fractions, a cytoplasmic extract (CE) representing cellular material soluble in 0.5% NP-40 and a particulate fraction (PF) insoluble in 0.5% NP-40 but soluble in 0.2% deoxycholate and 0.5% NP-40. Intracellular feline leukemia virus p30 was isolated from infected cells by immune precipitation with antiserum to p30 and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the precipitated proteins. Cells labeled for 3 h with [35S]methionine contained equal amounts of p30 in both the CE and the PF. p30 synthesis was estimated to be 0.8% of the total host cell protein synthesis. Immune precipitates from cell pulse labeled for 2.5 min contained a labeled 60,000-dalton polypeptide (Pp60) in the PF and a polypeptide in the CE that comigrated with feline leukemia virus p30 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When cells were chased after a pulse label, there was a rapid loss of Pp60 in the PF and an accumulation of p30 in the CE within 30 min followed by distribution of p30 in both the PF and the CE. Estimation of intracellular and extracellular p30 levels during a 0.5- to 24-h chase period suggested that most of the newly synthesized p30 was incorporated into extracellular virus. Typtic peptide analysis of labeled Pp60 and p30 demonstrated the presence of 13 of 15 p30 peptides within the Pp60 molecule. The tryptic peptide analysis in concert with the pulse-chase labeling data provides strong evidence that Pp60 is a precursor of p30."}
{"id": "PMID:185423", "title": "Infection of resistant avian cells by subgroup B Rous sarcoma virus.", "content": "Chicken fibroblasts derived from the H & N flock, which have been characterized as resistant to subgroup B avian oncornaviruses in focus assays, can be infected in suspension shortly after trypsinization by subgroup B sarcoma and leukosis viruses. Once cells are plated, resistance to infection reappears rapidly. C/BE cell suspensions obtained by treatment with EDTA instead of trypsin are not as sensitive to infection. Late interference established by preinfection with subgroup B leukosis viruses is not overcome by trypsinization. In addition to C/BE H & N chicken cells, C/ABE RPRL line 7 cells can also be infected by subgroup B viruses shortly after trypsinization; however, none of the cell types can be made sensitive to subgroup E infection. These results are discussed in relation to current information on the genetic control of resistance to avian oncornaviruses.", "contents": "Infection of resistant avian cells by subgroup B Rous sarcoma virus. Chicken fibroblasts derived from the H & N flock, which have been characterized as resistant to subgroup B avian oncornaviruses in focus assays, can be infected in suspension shortly after trypsinization by subgroup B sarcoma and leukosis viruses. Once cells are plated, resistance to infection reappears rapidly. C/BE cell suspensions obtained by treatment with EDTA instead of trypsin are not as sensitive to infection. Late interference established by preinfection with subgroup B leukosis viruses is not overcome by trypsinization. In addition to C/BE H & N chicken cells, C/ABE RPRL line 7 cells can also be infected by subgroup B viruses shortly after trypsinization; however, none of the cell types can be made sensitive to subgroup E infection. These results are discussed in relation to current information on the genetic control of resistance to avian oncornaviruses."}
{"id": "PMID:185424", "title": "Simian virus 40-permissive cell interactions: selection and characterization of spontaneously arising monkey cells that are resistant to simian virus 40 infection.", "content": "A fraction of permissive cells survive simian virus 40 (SV40) infection. The frequency of such surviving cells depends only upon the concentration of infecting virus, both parental and progeny, to which the cells are exposed during the course of selection. Surviving clones, which can be freed of virus by cloning in the presence of SV40 antiserum, are indistinguishable from parental cells in their growth of characteristics and display no SV40 antigen; thus they are not transformed. Most surviving clones are less than 10% as susceptible as parental cells to SV40 infection; 5 to 10% are less than 1% as susceptible. None of these SV40-resistant clones is absolutely resistant to SV40 infection. Analysis of 16 independently arising resistant clones indicates that they all block SV40 infection at an early stage after adsorption and eclipse but before full uncoating. Viral mutants have been isolated that partially overcome the block to infection in these cells; these host range viruses plaque on resistant lines fivefold more efficiently than wild-type SV40 and have a characteristic plaque morphology. Fluctuation analysis indicates that resistant cells arise spontaneously during the growth of normally susceptible permissive cells. Thus, SV40-resistant cells are selected for, not induced by, SV40 infection.", "contents": "Simian virus 40-permissive cell interactions: selection and characterization of spontaneously arising monkey cells that are resistant to simian virus 40 infection. A fraction of permissive cells survive simian virus 40 (SV40) infection. The frequency of such surviving cells depends only upon the concentration of infecting virus, both parental and progeny, to which the cells are exposed during the course of selection. Surviving clones, which can be freed of virus by cloning in the presence of SV40 antiserum, are indistinguishable from parental cells in their growth of characteristics and display no SV40 antigen; thus they are not transformed. Most surviving clones are less than 10% as susceptible as parental cells to SV40 infection; 5 to 10% are less than 1% as susceptible. None of these SV40-resistant clones is absolutely resistant to SV40 infection. Analysis of 16 independently arising resistant clones indicates that they all block SV40 infection at an early stage after adsorption and eclipse but before full uncoating. Viral mutants have been isolated that partially overcome the block to infection in these cells; these host range viruses plaque on resistant lines fivefold more efficiently than wild-type SV40 and have a characteristic plaque morphology. Fluctuation analysis indicates that resistant cells arise spontaneously during the growth of normally susceptible permissive cells. Thus, SV40-resistant cells are selected for, not induced by, SV40 infection."}
{"id": "PMID:185425", "title": "Herpes simplex virus gene expression in transformed cells. I. Regulation of the viral thymidine kinase gene in transformed L cells by products of superinfecting virus.", "content": "In this paper we show that the expression of the herpes simplex virus type 1 (HSV-1) gene for thymidine kinase (tk) in HSV-transformed cells is subject to regulation by two viral products synthesized during productive infection of these cells with a tk- mutant of HSV-1. The cell line used in this study is a derivative of tk-deficient mouse L cells that, after exposure to UV-inactivated HSV-1, had acquired the HSV-1 gene for tk (which we term a resident viral gene) and consequently expressed the tk+ phenotype (LVtk+ cells). Productive infection of these cells with HSV-1(tk-) at appropriate multiplicities caused significant enhancement of the viral tk activity. The results of several experiments allow us to conclude that this enhancement was due to increased synthesis of tk specified by the HSV-1 gene resident in the LVtk+ cells and that a specific protein made early after infection with HSV-1(tk-) mediated the enhancement, probably by increasing the production of mRNA from the viral tk gene resident in the LVtk+ cells. Our data also indicate that another HSV-1(tk-) product acted to turn off tk synthesis. The finding that tk activity continued to increase for a longer time after infection of the LVtk+ cells at 2 PFU/cell than after infection at higher multiplicities suggested the synthesis of a product which inhibited tk synthesis and whose concentration reached critical levels earlier at higher multiplicities of infection. Inhibition of DNA synthesis after infection, a treatment that depresses the synthesis of late viral proteins, prolonged the synthesis of tk in LVtk+ cells infected at either 2 or 5 PFU/cell. Infection of the LVtk+ cells with HSV-2(tk-) resulted in only small increases in tk activity, indicating some type specificity in recognition of viral products that can modify the expression of the HSV-1 tk gene resident in these cells.", "contents": "Herpes simplex virus gene expression in transformed cells. I. Regulation of the viral thymidine kinase gene in transformed L cells by products of superinfecting virus. In this paper we show that the expression of the herpes simplex virus type 1 (HSV-1) gene for thymidine kinase (tk) in HSV-transformed cells is subject to regulation by two viral products synthesized during productive infection of these cells with a tk- mutant of HSV-1. The cell line used in this study is a derivative of tk-deficient mouse L cells that, after exposure to UV-inactivated HSV-1, had acquired the HSV-1 gene for tk (which we term a resident viral gene) and consequently expressed the tk+ phenotype (LVtk+ cells). Productive infection of these cells with HSV-1(tk-) at appropriate multiplicities caused significant enhancement of the viral tk activity. The results of several experiments allow us to conclude that this enhancement was due to increased synthesis of tk specified by the HSV-1 gene resident in the LVtk+ cells and that a specific protein made early after infection with HSV-1(tk-) mediated the enhancement, probably by increasing the production of mRNA from the viral tk gene resident in the LVtk+ cells. Our data also indicate that another HSV-1(tk-) product acted to turn off tk synthesis. The finding that tk activity continued to increase for a longer time after infection of the LVtk+ cells at 2 PFU/cell than after infection at higher multiplicities suggested the synthesis of a product which inhibited tk synthesis and whose concentration reached critical levels earlier at higher multiplicities of infection. Inhibition of DNA synthesis after infection, a treatment that depresses the synthesis of late viral proteins, prolonged the synthesis of tk in LVtk+ cells infected at either 2 or 5 PFU/cell. Infection of the LVtk+ cells with HSV-2(tk-) resulted in only small increases in tk activity, indicating some type specificity in recognition of viral products that can modify the expression of the HSV-1 tk gene resident in these cells."}
{"id": "PMID:185426", "title": "Mouse strain resistant to N-, B-, and NB-tropic murine leukemia viruses.", "content": "Mouse strain G was studied for its susceptibility to various strains of murine leukemia and sarcoma viruses. Both N- and NB-tropic Friend leukemia viruses neither induced splenomegaly nor grew efficiently in strain G mice. Using the XC test, cultured embryo cells were found to be resistant, but not absolutely, to all the tested viruses, N-tropic AKR virus, N- and NB-tropic Friend leukemia viruses, NB-tropic Rauscher leukemia virus, B-tropic WN1802B virus, NB-tropic Moloney leukemia and sarcoma viruses, and N-tropic Kirsten sarcoma virus, although the resistance to Moloney leukemia and sarcoma viruses is sometimes not as strong as that for other viruses. Thus, the strain G mice are unique among mouse strains because they show resistance that is not related to the N-B tropism of murine leukemia viruses.", "contents": "Mouse strain resistant to N-, B-, and NB-tropic murine leukemia viruses. Mouse strain G was studied for its susceptibility to various strains of murine leukemia and sarcoma viruses. Both N- and NB-tropic Friend leukemia viruses neither induced splenomegaly nor grew efficiently in strain G mice. Using the XC test, cultured embryo cells were found to be resistant, but not absolutely, to all the tested viruses, N-tropic AKR virus, N- and NB-tropic Friend leukemia viruses, NB-tropic Rauscher leukemia virus, B-tropic WN1802B virus, NB-tropic Moloney leukemia and sarcoma viruses, and N-tropic Kirsten sarcoma virus, although the resistance to Moloney leukemia and sarcoma viruses is sometimes not as strong as that for other viruses. Thus, the strain G mice are unique among mouse strains because they show resistance that is not related to the N-B tropism of murine leukemia viruses."}
{"id": "PMID:185427", "title": "Enzymatic basis for the selective inhibition of varicella-zoster virus by 5-halogenated analogues of deoxycytidine.", "content": "5-Bromodeoxycytidine (BrdC) and 5-iododeoxycytidine, at a concentration of 100 mug/ml, effectively inhibit the replication of varicella-zoster (VZ) virus in tissue culture. No toxicity could be demonstrated in uninfected cells under the same conditions. Studies on the enzymatic basis for this selective inhibition were undertaken. Infection of human embryonic lung cell monolayers with VZ virus-infected cells results in the induction of thymidine (dT), deoxycytidine (dC), and BrdC kinase activities (which are increased 10-, 40-, and 60-fold, respectively) and in a 70-fold stimulation in the incorporation of 3H nucleotide (5-bromodeoxyuridylate) derived from BrdC into DNA. The thermal stability of the VZ virus-induced activities differs significantly from the activities induced by herpes simplex virus type 1 and herpes simplex virus type 2 and those present in uninfected human embryonic lung cells. The VZ virus-induced dT, dC, and BrdC kinase are similarly affected by temperature and cofractionate upon Sephadex gel filtration, findings consistent with the hypothesis that these activities are the function of a single enzyme: a pyrimidine deoxyribonucleoside kinase. The molecular weight, calculated on the basis of the elution pattern on Sephadex G-150, is 70,000. Kinetic studies, demonstrating that dT and dC competively inhibit the phosphorylation of BrdC, are consistent with the phosphorylation of these substrates at a common active site. Kinetic parameters include: KidT = 0.6 MUM; KidC = 60 muM; KmBrdC = 8.5 muM. In contrast to its relatively high affinity for the VZ virus-induced kinase, BrdC is a relatively poor substrate for the host kinases. Therefore, the basis for the selective inhibition of VZ virus by 5-halogenated analogues of dC is reflected in the induction of a pyrimidine deoxyribonucleoside kinase with a high affinity for BrdC.", "contents": "Enzymatic basis for the selective inhibition of varicella-zoster virus by 5-halogenated analogues of deoxycytidine. 5-Bromodeoxycytidine (BrdC) and 5-iododeoxycytidine, at a concentration of 100 mug/ml, effectively inhibit the replication of varicella-zoster (VZ) virus in tissue culture. No toxicity could be demonstrated in uninfected cells under the same conditions. Studies on the enzymatic basis for this selective inhibition were undertaken. Infection of human embryonic lung cell monolayers with VZ virus-infected cells results in the induction of thymidine (dT), deoxycytidine (dC), and BrdC kinase activities (which are increased 10-, 40-, and 60-fold, respectively) and in a 70-fold stimulation in the incorporation of 3H nucleotide (5-bromodeoxyuridylate) derived from BrdC into DNA. The thermal stability of the VZ virus-induced activities differs significantly from the activities induced by herpes simplex virus type 1 and herpes simplex virus type 2 and those present in uninfected human embryonic lung cells. The VZ virus-induced dT, dC, and BrdC kinase are similarly affected by temperature and cofractionate upon Sephadex gel filtration, findings consistent with the hypothesis that these activities are the function of a single enzyme: a pyrimidine deoxyribonucleoside kinase. The molecular weight, calculated on the basis of the elution pattern on Sephadex G-150, is 70,000. Kinetic studies, demonstrating that dT and dC competively inhibit the phosphorylation of BrdC, are consistent with the phosphorylation of these substrates at a common active site. Kinetic parameters include: KidT = 0.6 MUM; KidC = 60 muM; KmBrdC = 8.5 muM. In contrast to its relatively high affinity for the VZ virus-induced kinase, BrdC is a relatively poor substrate for the host kinases. Therefore, the basis for the selective inhibition of VZ virus by 5-halogenated analogues of dC is reflected in the induction of a pyrimidine deoxyribonucleoside kinase with a high affinity for BrdC."}
{"id": "PMID:185428", "title": "Anatomy of herpes simplex virus DNA. VI. Defective DNA originates from the S component.", "content": "We previously reported that serial propagation of the Justin strain of herpes simplex virus 1 [HSV-1 (Justin)] results in the generation of defective DNA molecules consisting of tandem repetitions of sequences of limited complexity. In the present study, HSV-1 DNA was cleaved with the restriction endonucleases BglII and EcoRI. The fragments were electrophoretically separated on agarose gels, transferred to nitrocellulose strips, and then hybridized with 32P-labeled HSV-1 (Justin) defective DNA. The data allow us to conclude that DNA sequences contained in the repeat unit of defective DNA originate from the S segment of the wild-type viral DNA molecule.", "contents": "Anatomy of herpes simplex virus DNA. VI. Defective DNA originates from the S component. We previously reported that serial propagation of the Justin strain of herpes simplex virus 1 [HSV-1 (Justin)] results in the generation of defective DNA molecules consisting of tandem repetitions of sequences of limited complexity. In the present study, HSV-1 DNA was cleaved with the restriction endonucleases BglII and EcoRI. The fragments were electrophoretically separated on agarose gels, transferred to nitrocellulose strips, and then hybridized with 32P-labeled HSV-1 (Justin) defective DNA. The data allow us to conclude that DNA sequences contained in the repeat unit of defective DNA originate from the S segment of the wild-type viral DNA molecule."}
{"id": "PMID:185429", "title": "Two adenovirus type 2-simian virus 40 hybrid populations that contain the entire SV40 genome differ in their ability to induce SV40 transplantation immunity in hamsters but not in mice.", "content": "Ad2++ HEY and Ad2++ LEY are two adenovirus 2(Ad2)-simian virus 40 (SV40) hybrids distinguished by differences in the efficiency with which they produce SV40 progeny in lytically infected African green monkey kidney cells. These virus populations are composed of nonhybrid Ad2 and hybrid virions, the majority of which contain more than 1 unit of SV40 DNA. The Ad2++ HEY and LEY populations also differ in their ability to induce SV40 transplantation immunity in rodents. Only Ad2++ HEY induces SV40 transplantation immunity in hamsters, whereas both viruses induce significant SV40 transplantation immunity in adult BALB/c mice.", "contents": "Two adenovirus type 2-simian virus 40 hybrid populations that contain the entire SV40 genome differ in their ability to induce SV40 transplantation immunity in hamsters but not in mice. Ad2++ HEY and Ad2++ LEY are two adenovirus 2(Ad2)-simian virus 40 (SV40) hybrids distinguished by differences in the efficiency with which they produce SV40 progeny in lytically infected African green monkey kidney cells. These virus populations are composed of nonhybrid Ad2 and hybrid virions, the majority of which contain more than 1 unit of SV40 DNA. The Ad2++ HEY and LEY populations also differ in their ability to induce SV40 transplantation immunity in rodents. Only Ad2++ HEY induces SV40 transplantation immunity in hamsters, whereas both viruses induce significant SV40 transplantation immunity in adult BALB/c mice."}
{"id": "PMID:185430", "title": "Urologic abdominal masses in infants and children.", "content": "A series of 167 infants and children presenting with palpable urologic abdominal masses from 1960 to 1973 has been reviewed. The groupings by age at presentation and type of urologic lesion enable us to make certain general statements. Emphasis is placed upon adequate preoperative evaluation in any child with an abdominal mass to avoid unnecessary laparotomy and morbidity.", "contents": "Urologic abdominal masses in infants and children. A series of 167 infants and children presenting with palpable urologic abdominal masses from 1960 to 1973 has been reviewed. The groupings by age at presentation and type of urologic lesion enable us to make certain general statements. Emphasis is placed upon adequate preoperative evaluation in any child with an abdominal mass to avoid unnecessary laparotomy and morbidity."}
{"id": "PMID:185432", "title": "Cerebrospinal fluid IgG level in herpes simplex encephalitis.", "content": "Elevated levels of immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) were associated with elevated herpes antibody in the CSF in a case of herpes simplex encephalitis. The case was also characterized by a prolonged course and a difficult virus isolation.", "contents": "Cerebrospinal fluid IgG level in herpes simplex encephalitis. Elevated levels of immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) were associated with elevated herpes antibody in the CSF in a case of herpes simplex encephalitis. The case was also characterized by a prolonged course and a difficult virus isolation."}
{"id": "PMID:185441", "title": "Difference in response to mouse hepatitis virus among susceptible mouse strains.", "content": "After intraperitoneal inoculation with a high-virulent mouse hepatitis virus (MHV) a significant difference was seen in survival time between DDD and CDF1 (BALB/c X DDD) mice, while 50% lethal doses were not significantly different. With 3 X 10(3) PFU of the virus CDF1 and DDD mice died in 45 and 120 hr, respectively, on the average. This difference of susceptibility between DDD and CDF1 mice was first demonstrable at the age of 1 week and was more pronounced at the age of 4 weeks but showed no dependence of the sex. Virus titers ran 2 to 3 log higher in the liver and blood of CDF1 than in those of DDD mice, while being only 1 log higher in the spleen. At an early stage of infection viral antigen was demonstrable by immunofluorescence in sinusoidal lining cells of the liver more prominently in VDF1 than in DDD mice. Interferon production occurring in parallel with virus growth was significantly higher in CDF1 than in DDD mice. In DDD mice, liver lesions were rather focal with some accumulation of round cells, while they were confluent with poor cellular response in CDF1 mice. Viral growth in cultured peritoneal macrophages from CDF1 mice was 1 log higher than in those from DDD mice. The results suggest that the divergence in response to MHV among susceptible mice greatly depends upon the susceptibility of macrophages and reticuloendothelial cells which constitute primary targets of the virus.", "contents": "Difference in response to mouse hepatitis virus among susceptible mouse strains. After intraperitoneal inoculation with a high-virulent mouse hepatitis virus (MHV) a significant difference was seen in survival time between DDD and CDF1 (BALB/c X DDD) mice, while 50% lethal doses were not significantly different. With 3 X 10(3) PFU of the virus CDF1 and DDD mice died in 45 and 120 hr, respectively, on the average. This difference of susceptibility between DDD and CDF1 mice was first demonstrable at the age of 1 week and was more pronounced at the age of 4 weeks but showed no dependence of the sex. Virus titers ran 2 to 3 log higher in the liver and blood of CDF1 than in those of DDD mice, while being only 1 log higher in the spleen. At an early stage of infection viral antigen was demonstrable by immunofluorescence in sinusoidal lining cells of the liver more prominently in VDF1 than in DDD mice. Interferon production occurring in parallel with virus growth was significantly higher in CDF1 than in DDD mice. In DDD mice, liver lesions were rather focal with some accumulation of round cells, while they were confluent with poor cellular response in CDF1 mice. Viral growth in cultured peritoneal macrophages from CDF1 mice was 1 log higher than in those from DDD mice. The results suggest that the divergence in response to MHV among susceptible mice greatly depends upon the susceptibility of macrophages and reticuloendothelial cells which constitute primary targets of the virus."}
{"id": "PMID:185442", "title": "Enhanced growth and plaquing of rabies virus in static chick embryo cell culture.", "content": "The 7-day egg passage line of HEP Flury strain of rabies virus was inoculated to primary chick embyro (CE) cells prepared in different ways to compared efficiencies of viral growth and plaquing. Special care to minimize cellular damage due to trypsin at the step of monodispersion and sowing a comparatively large number of cells for monolayer preparation were required for rabies plaquing, whereas such cares were not necessary for plaquing of vesicular stomatitis virus. Plaque number and size were increased by incorporation of a high concentration of thymidine into cell growth medium. Various other means to produce a static state of CE cells were tested, and a maximal plaquing efficiency was obtained when dishes receiving a massive number of dispersed cells in MEM plus 1% calf serum were incubated at 37 C for 1 day without any buffering for monolayer preparation and postinfection incubation was done at 32 C in a CO2-incubator. Bottle cultures of CE cells prepared in a similar manner, when infected with HEP Flury virus, yielded a markedly higher titer of virus that CE cells prepared by our previous standard method.", "contents": "Enhanced growth and plaquing of rabies virus in static chick embryo cell culture. The 7-day egg passage line of HEP Flury strain of rabies virus was inoculated to primary chick embyro (CE) cells prepared in different ways to compared efficiencies of viral growth and plaquing. Special care to minimize cellular damage due to trypsin at the step of monodispersion and sowing a comparatively large number of cells for monolayer preparation were required for rabies plaquing, whereas such cares were not necessary for plaquing of vesicular stomatitis virus. Plaque number and size were increased by incorporation of a high concentration of thymidine into cell growth medium. Various other means to produce a static state of CE cells were tested, and a maximal plaquing efficiency was obtained when dishes receiving a massive number of dispersed cells in MEM plus 1% calf serum were incubated at 37 C for 1 day without any buffering for monolayer preparation and postinfection incubation was done at 32 C in a CO2-incubator. Bottle cultures of CE cells prepared in a similar manner, when infected with HEP Flury virus, yielded a markedly higher titer of virus that CE cells prepared by our previous standard method."}
{"id": "PMID:185447", "title": "[Comparative characteristics of the lipoproteins of the human vascular wall and blood plasma].", "content": "Electrophoresis in the polyacrylamide gel and ultracentrifugation with a multistage density gradient demonstrated virtually the whole of the blood plasma lipoproteids spectrum to be contained in the human aortal wall. An immunological identity of the whole beta- and alpha-lipoproteids and also of their individual apoproteins in the aortal wall and blood plasma was ascertained. Moreover, the ratio of etherified cholesterol/total cholesterol in the vascular and plasmatic lipoproteids proved to be quiet close. In determining the content of the summary pre-beta-and beta-lipoproteids in the aortal wall the quantity of the said lipoproteids in atherosclerotic lesions was found several times as high as in a normal aorta, whereas the lipoproteids concentration in an intact aortal wall correlated with the intensity of atherosclerosis in the same aorta. The data obtained bear evidence to a plasmatic origin of lipoproteids in the vascular wall and to their important role in atherogenesis.", "contents": "[Comparative characteristics of the lipoproteins of the human vascular wall and blood plasma]. Electrophoresis in the polyacrylamide gel and ultracentrifugation with a multistage density gradient demonstrated virtually the whole of the blood plasma lipoproteids spectrum to be contained in the human aortal wall. An immunological identity of the whole beta- and alpha-lipoproteids and also of their individual apoproteins in the aortal wall and blood plasma was ascertained. Moreover, the ratio of etherified cholesterol/total cholesterol in the vascular and plasmatic lipoproteids proved to be quiet close. In determining the content of the summary pre-beta-and beta-lipoproteids in the aortal wall the quantity of the said lipoproteids in atherosclerotic lesions was found several times as high as in a normal aorta, whereas the lipoproteids concentration in an intact aortal wall correlated with the intensity of atherosclerosis in the same aorta. The data obtained bear evidence to a plasmatic origin of lipoproteids in the vascular wall and to their important role in atherogenesis."}
{"id": "PMID:185448", "title": "[Use of miskleron in ischemic heart disease with differing types of hyperlipoproteinemias].", "content": "The effect of Misclerone (clofibrate) was studied in 127 patients with different types of hyperlipoproteinemia treated with the drug for 1 month and longer. On the basis of the obtained data it was concluded that Misclerone is effective both in patients with isolated disorders in cholesterol metabolism (Type II), and in those with cholesterol and triglycerides metabolism disorders (Types IIb and III), and in those with prevailing triglycerides metabolism disorders (Type IV). The efficacy of the drug in Type II hyperlipoproteinemia is determined by the degree and nature of metabolic disorders of low density lipoproteins.", "contents": "[Use of miskleron in ischemic heart disease with differing types of hyperlipoproteinemias]. The effect of Misclerone (clofibrate) was studied in 127 patients with different types of hyperlipoproteinemia treated with the drug for 1 month and longer. On the basis of the obtained data it was concluded that Misclerone is effective both in patients with isolated disorders in cholesterol metabolism (Type II), and in those with cholesterol and triglycerides metabolism disorders (Types IIb and III), and in those with prevailing triglycerides metabolism disorders (Type IV). The efficacy of the drug in Type II hyperlipoproteinemia is determined by the degree and nature of metabolic disorders of low density lipoproteins."}
{"id": "PMID:185450", "title": "[Clinical and morphological studies in a case of congenital glaucoma combined with an ocular-dental-digital dysplasia (author's transl)].", "content": "Clinical and morphological studies were undertaken to characterize a case of congenital glaucoma combined with an ocular-dental-digital dysplasia in a two year old patient. Light and electromicroscopic investigations of a surgically removed trabecular specimen were carried out. A trabeculotomy had been performed at this exact site 10 months prior to removal. The existence of a canal of Schlemm was demonstrated. The regular trabecular meshwork and trabecular region was replaced by fairly dense scar tissue, containing rudimentary intertrabecular spaces. Proliferating corneal endothelial cells covered the wound area up to the uveal part of the trabecular region. The morphological findings correlated well with the clinical observation of continued raised intraocular pressure despite trabeculotomy. It is concluded that, contrary to the situation in adult onset glaucoma, the strong proliferative tendency of juvenile tissue has a marked influence on the postoperative efficacy of the trabeculotomy.", "contents": "[Clinical and morphological studies in a case of congenital glaucoma combined with an ocular-dental-digital dysplasia (author's transl)]. Clinical and morphological studies were undertaken to characterize a case of congenital glaucoma combined with an ocular-dental-digital dysplasia in a two year old patient. Light and electromicroscopic investigations of a surgically removed trabecular specimen were carried out. A trabeculotomy had been performed at this exact site 10 months prior to removal. The existence of a canal of Schlemm was demonstrated. The regular trabecular meshwork and trabecular region was replaced by fairly dense scar tissue, containing rudimentary intertrabecular spaces. Proliferating corneal endothelial cells covered the wound area up to the uveal part of the trabecular region. The morphological findings correlated well with the clinical observation of continued raised intraocular pressure despite trabeculotomy. It is concluded that, contrary to the situation in adult onset glaucoma, the strong proliferative tendency of juvenile tissue has a marked influence on the postoperative efficacy of the trabeculotomy."}
{"id": "PMID:185451", "title": "[Total syndactylism with mesomelic shortening of the arm, radioulnar and metacarpal synostoses and disorganization of the phalanges (\"cenani syndactylism\") (author's transl)].", "content": "An additional case \"Cenani syndactylism\" in a 7 years-old female child was described. With this autosomal recessive inherited disease, the radius and ulna are severly shortened and generally fused with each other. The metacarpal bones are, for the most part, synostosized. The phalanges are badly disorganized. Usually no fingers can be recognized externally. The alterations in the feet are far less pronounced. Syndactylism and ray reduction are frequent. A similar, but apparently independent, case with radioulnar synstostoses, reduction, dysplasia and fusion of the metacarpal bones but less pronounced malformations of the fingers was also described. Finally, new type of malformation was present for comparison in which an increased number of metacarpi and metatarsi and, to some extent, severely disorganized phalanges with massive syndactylism are present. The etiology of the second and third cases could not be explained.", "contents": "[Total syndactylism with mesomelic shortening of the arm, radioulnar and metacarpal synostoses and disorganization of the phalanges (\"cenani syndactylism\") (author's transl)]. An additional case \"Cenani syndactylism\" in a 7 years-old female child was described. With this autosomal recessive inherited disease, the radius and ulna are severly shortened and generally fused with each other. The metacarpal bones are, for the most part, synostosized. The phalanges are badly disorganized. Usually no fingers can be recognized externally. The alterations in the feet are far less pronounced. Syndactylism and ray reduction are frequent. A similar, but apparently independent, case with radioulnar synstostoses, reduction, dysplasia and fusion of the metacarpal bones but less pronounced malformations of the fingers was also described. Finally, new type of malformation was present for comparison in which an increased number of metacarpi and metatarsi and, to some extent, severely disorganized phalanges with massive syndactylism are present. The etiology of the second and third cases could not be explained."}
{"id": "PMID:185452", "title": "[Plasma-cAMP in primary and secondary hyperparathyroidism (author's transl)].", "content": "3 patients with operatively proven primary hyperparathyroidism showed normal plasma cAMP concentrations. 5 patients in chronic dialysis treatment independent of the level of parathyroid hormone had increased plasma cAMP concentrations. These observations suggest that there is under these circumstances no regulation of plasma cAMP by the parathyroid hormone.", "contents": "[Plasma-cAMP in primary and secondary hyperparathyroidism (author's transl)]. 3 patients with operatively proven primary hyperparathyroidism showed normal plasma cAMP concentrations. 5 patients in chronic dialysis treatment independent of the level of parathyroid hormone had increased plasma cAMP concentrations. These observations suggest that there is under these circumstances no regulation of plasma cAMP by the parathyroid hormone."}
{"id": "PMID:185453", "title": "Physiological responses to stress with reference to the domestic fowl.", "content": "Environmental stress may effect the outcome of routine investigations as well as experimental procedures. This is illustrated by investigations in the domestic fowl.", "contents": "Physiological responses to stress with reference to the domestic fowl. Environmental stress may effect the outcome of routine investigations as well as experimental procedures. This is illustrated by investigations in the domestic fowl."}
{"id": "PMID:185454", "title": "Differences in tumor incidence in two substrains of Claude BALB/c (BALB/cfCd) mice, emphasizing renal, mammary, pancreatic, and synovial tumors.", "content": "Observations were made on the tumor incidences in two substrains of the BALB/CFCd mouse. A total of 900 mice were examined. They comprised two substrains (families), direct descendants of two different females (designated 916 and 917) of the 31st inbred generation. Offspring of sibling matings of the fourth and fifth generation descendants of these two females were killed when moribund or when they had visible or palpable masses. Complete gross and microscopic examinations were conducted. Renal tumors were noted in 48.1% of those necropsied in family 916 and in 24.6% of those in family 917 (p less than .025). Mammary tumors were found in 13.3% of family 917 and in 3.3% of family 916 (p less than .001). Neoplasms of the reticulo-endothelial system (reticulum cell neoplasms, lymphocytic leukemia, other lymphocytic neoplasms) were found in 20.0% of family 917 but only in 11.2% of family 916 (p less than .005). Tumors of the respiratory system (primarily alveolar adenomas and alveolar adenocarcinomas) were found in 10.2% of family 916 and 16.5% of family 917 (p less than .05). Less commonly observed tumors included synoviomas, 7.6% in family 916 versus 2.1% in 917 (p less than .005), and seven pancreatic acinar adenomas, all but one of which were found in family 916. Also recorded were a total of nine myoepitheliomas, 28 hemangioendotheliomas, two interstitial cell tumors of the testis, a single mesothelioma and a single rhabdomyosarcoma of the esophagus. Degenerative lesions consisting of kyphoscoliosis were noted in 3.7% of mice examined in both families combined.", "contents": "Differences in tumor incidence in two substrains of Claude BALB/c (BALB/cfCd) mice, emphasizing renal, mammary, pancreatic, and synovial tumors. Observations were made on the tumor incidences in two substrains of the BALB/CFCd mouse. A total of 900 mice were examined. They comprised two substrains (families), direct descendants of two different females (designated 916 and 917) of the 31st inbred generation. Offspring of sibling matings of the fourth and fifth generation descendants of these two females were killed when moribund or when they had visible or palpable masses. Complete gross and microscopic examinations were conducted. Renal tumors were noted in 48.1% of those necropsied in family 916 and in 24.6% of those in family 917 (p less than .025). Mammary tumors were found in 13.3% of family 917 and in 3.3% of family 916 (p less than .001). Neoplasms of the reticulo-endothelial system (reticulum cell neoplasms, lymphocytic leukemia, other lymphocytic neoplasms) were found in 20.0% of family 917 but only in 11.2% of family 916 (p less than .005). Tumors of the respiratory system (primarily alveolar adenomas and alveolar adenocarcinomas) were found in 10.2% of family 916 and 16.5% of family 917 (p less than .05). Less commonly observed tumors included synoviomas, 7.6% in family 916 versus 2.1% in 917 (p less than .005), and seven pancreatic acinar adenomas, all but one of which were found in family 916. Also recorded were a total of nine myoepitheliomas, 28 hemangioendotheliomas, two interstitial cell tumors of the testis, a single mesothelioma and a single rhabdomyosarcoma of the esophagus. Degenerative lesions consisting of kyphoscoliosis were noted in 3.7% of mice examined in both families combined."}
{"id": "PMID:185455", "title": "The agouti (Dasyprocta sp) in biomedical research and captivity.", "content": "Agoutis (Dasyprocta sp) are hystricomorph rodents belonging to the family Dasyproctidae. Utilization of agoutis in a research program of the National Institutes of Health necessitated the development of suitable methods for feeding, housing and collecting blood. The rodents were maintained successfully in conventional dog cages and kennels, and thrived on a diet of primate diet and apples. Physical examinations and periodic blood collections were best performed while agoutis were sedated with ketamine HCl (42-83 mg/kg, intramuscularly). Satisfactory sites for blood sampling were the cephalic, saphenous and jugular veins. Hematologic and serum chemical values established for the agouti were similar to those found in other rodents. Experimentally induced and naturally occurring diseases of agoutis were reviewed.", "contents": "The agouti (Dasyprocta sp) in biomedical research and captivity. Agoutis (Dasyprocta sp) are hystricomorph rodents belonging to the family Dasyproctidae. Utilization of agoutis in a research program of the National Institutes of Health necessitated the development of suitable methods for feeding, housing and collecting blood. The rodents were maintained successfully in conventional dog cages and kennels, and thrived on a diet of primate diet and apples. Physical examinations and periodic blood collections were best performed while agoutis were sedated with ketamine HCl (42-83 mg/kg, intramuscularly). Satisfactory sites for blood sampling were the cephalic, saphenous and jugular veins. Hematologic and serum chemical values established for the agouti were similar to those found in other rodents. Experimentally induced and naturally occurring diseases of agoutis were reviewed."}
{"id": "PMID:185456", "title": "Biological values of the infant, juvenile, and adult agouti (Dasyprocta sp) with emphasis on microbial flora.", "content": "Normal values for intestinal flora were determined on four adult, two juvenile, and four infant agoutis (Dasyprocta sp) maintained at our institution. Serologic, hematologic, biochemical, and histologic observations were also made on these same agoutis, and serologic, microbiologic, and endoparasitic tests were made on serum and fecal samples from agoutis maintained at other institutions. Streptococci, lactobacilli and nonenteropathogenic Escherichia coli were isolated from cecal contents of all age groups. Gaffkya tetragena and Bacillus sp were recovered from infant agoutis, Proteus mirabilis from juvenile agoutis, and Proteus mirabilis and Micrococcus sp from adult agoutis. Infant agoutis showed marginal antibody titers to reovirus type 3 and Toolan's H-1 viruses, and Theiler's GDVII antibodies were detected in juvenile agoutis, but no antibody titers to murine viruses were found in the adult agoutis maintained at our institution. Hematologic, biochemical, and histologic data for these agoutis were comparable to those of other hystricomorph rodents. Serologic tests of the agoutis maintained at other institutions disclosed antibodies for GDVII virus in all of 17 animals tested, while marginal titers were found for Sendai virus in four and for reovirus type 3 in eight of the 17 animals. Only low incidences of pathogenic bacteria (Salmonella, Pseudomonas, and Citrobacter) were isolated from the agoutis maintained elsewhere. The endoparasites found in these agoutis were Ascaris, Toxascaris, Strongyloides, Trichuris, and Trichomonas.", "contents": "Biological values of the infant, juvenile, and adult agouti (Dasyprocta sp) with emphasis on microbial flora. Normal values for intestinal flora were determined on four adult, two juvenile, and four infant agoutis (Dasyprocta sp) maintained at our institution. Serologic, hematologic, biochemical, and histologic observations were also made on these same agoutis, and serologic, microbiologic, and endoparasitic tests were made on serum and fecal samples from agoutis maintained at other institutions. Streptococci, lactobacilli and nonenteropathogenic Escherichia coli were isolated from cecal contents of all age groups. Gaffkya tetragena and Bacillus sp were recovered from infant agoutis, Proteus mirabilis from juvenile agoutis, and Proteus mirabilis and Micrococcus sp from adult agoutis. Infant agoutis showed marginal antibody titers to reovirus type 3 and Toolan's H-1 viruses, and Theiler's GDVII antibodies were detected in juvenile agoutis, but no antibody titers to murine viruses were found in the adult agoutis maintained at our institution. Hematologic, biochemical, and histologic data for these agoutis were comparable to those of other hystricomorph rodents. Serologic tests of the agoutis maintained at other institutions disclosed antibodies for GDVII virus in all of 17 animals tested, while marginal titers were found for Sendai virus in four and for reovirus type 3 in eight of the 17 animals. Only low incidences of pathogenic bacteria (Salmonella, Pseudomonas, and Citrobacter) were isolated from the agoutis maintained elsewhere. The endoparasites found in these agoutis were Ascaris, Toxascaris, Strongyloides, Trichuris, and Trichomonas."}
{"id": "PMID:185458", "title": "Pathogenesis of visna. I. Sequential virologic, serologic, and pathologic studies.", "content": "A total of 56 Icelandic sheep were infected with visna virus by intracerebral injection of strain 1514 and the course of infection was followed for 12 months. Virus was isolated from more than 90 per cent of the animals, primarily from central nervous system and lymphoid tissues. However, titers of free infectious virus were minimal and virus isolation often required the use of tissue explants. All sheep raised serum-neutralizing and complement-fixing antibodies beginning 1 to 3 months after infection. Differences in neutralization titers against the infecting strain (1514) and a reference strain (796) suggested that antigenic drift might occur during prolonged infection. High cerebrospinal fluid neutralization titers in the spinal fluid indicated local antibody production in the central nervous system. Although the incidence of clinical disease during the 1st year of infection was less that 10 per cent, approximately 80 per cent of the sheep examined had central nervous system histologic lesions of variable severity, which were marked 1 month after infection with little progression during the subsequent year. There was a striking correlation between the severity of central nervous system lesions and the frequency of virus isolations from all tissues. These observations provide detailed base line data on visna infection, suggest some of the mechanisms responsible for the persistence of infection and for the slowness and irregularity of disease occurrence, and form the basis for further experiments on the role of immunologic mechanisms in the pathogenesis of this slow infection.", "contents": "Pathogenesis of visna. I. Sequential virologic, serologic, and pathologic studies. A total of 56 Icelandic sheep were infected with visna virus by intracerebral injection of strain 1514 and the course of infection was followed for 12 months. Virus was isolated from more than 90 per cent of the animals, primarily from central nervous system and lymphoid tissues. However, titers of free infectious virus were minimal and virus isolation often required the use of tissue explants. All sheep raised serum-neutralizing and complement-fixing antibodies beginning 1 to 3 months after infection. Differences in neutralization titers against the infecting strain (1514) and a reference strain (796) suggested that antigenic drift might occur during prolonged infection. High cerebrospinal fluid neutralization titers in the spinal fluid indicated local antibody production in the central nervous system. Although the incidence of clinical disease during the 1st year of infection was less that 10 per cent, approximately 80 per cent of the sheep examined had central nervous system histologic lesions of variable severity, which were marked 1 month after infection with little progression during the subsequent year. There was a striking correlation between the severity of central nervous system lesions and the frequency of virus isolations from all tissues. These observations provide detailed base line data on visna infection, suggest some of the mechanisms responsible for the persistence of infection and for the slowness and irregularity of disease occurrence, and form the basis for further experiments on the role of immunologic mechanisms in the pathogenesis of this slow infection."}
{"id": "PMID:185467", "title": "Data attrition in follow-up studies of alcoholics.", "content": "Alcoholics who responded to posttreatment follow-up evaluation showed more improvement than those wh did not respond. Thus nonresponders may bias follow-up research tht does not account for missing data. Several procedures are outlined to increase follow-up return.", "contents": "Data attrition in follow-up studies of alcoholics. Alcoholics who responded to posttreatment follow-up evaluation showed more improvement than those wh did not respond. Thus nonresponders may bias follow-up research tht does not account for missing data. Several procedures are outlined to increase follow-up return."}
{"id": "PMID:185468", "title": "A telephone follow-up procedure for increasing the effectiveness of a treatment program for alcoholics.", "content": "The use of outpatient services by alcoholics can be significantly increased by means of a telephone follow-up procedure.", "contents": "A telephone follow-up procedure for increasing the effectiveness of a treatment program for alcoholics. The use of outpatient services by alcoholics can be significantly increased by means of a telephone follow-up procedure."}
{"id": "PMID:185470", "title": "The metabolism of carbohydrate.", "content": "The purpose of this review has been to establish a background in carbohydrate biochemistry as it relates to the human neonate. The emphasis has therefore been placed on the developing human, although many concepts are derived from studies in animal models. Further discussions of the physiology of carbohydrate metabolism are included in the chapters that follow.", "contents": "The metabolism of carbohydrate. The purpose of this review has been to establish a background in carbohydrate biochemistry as it relates to the human neonate. The emphasis has therefore been placed on the developing human, although many concepts are derived from studies in animal models. Further discussions of the physiology of carbohydrate metabolism are included in the chapters that follow."}
{"id": "PMID:185472", "title": "Myocardial ischemia.", "content": "Myocardial ischemia results from an imbalance of energy supply and demand. Because of the essentially aerobic nature of myocardial metabolism and the high oxygen extraction from the blood, ischemia is usually equatable with limitation of blood supply. Coronary atherosclerosis is a patchy disorder, and therefore, ischemia usually occurs in segmental fashion throughout the topography of the heart. Ischemia is invariably seen earliest and most intensely in the deep or subendocardial layers of myocardium. Ischemia leads to biochemical disruption, including initiation of glycolysis, which in turn causes electrophysiological and mechanical disturbances. Myocardial ischemia can be induced naturally or experimentally in the human subject in a variety of ways, some of which have been studied in the laboratory.", "contents": "Myocardial ischemia. Myocardial ischemia results from an imbalance of energy supply and demand. Because of the essentially aerobic nature of myocardial metabolism and the high oxygen extraction from the blood, ischemia is usually equatable with limitation of blood supply. Coronary atherosclerosis is a patchy disorder, and therefore, ischemia usually occurs in segmental fashion throughout the topography of the heart. Ischemia is invariably seen earliest and most intensely in the deep or subendocardial layers of myocardium. Ischemia leads to biochemical disruption, including initiation of glycolysis, which in turn causes electrophysiological and mechanical disturbances. Myocardial ischemia can be induced naturally or experimentally in the human subject in a variety of ways, some of which have been studied in the laboratory."}
{"id": "PMID:185473", "title": "[Abrikossof's tumor of a toe].", "content": "A case of Abrikossof tumor in a 33 year old patient presenting a progressive growth of a toe without associated pain or inflamation. There was an important hypertrophy of the affected toe with hyperkeratosis and pseudoelephantiasis. The histologic examination showed a massive infiltration of granular cells in the dermis. The exceptional localisation of the tumor in this case is emphasized.", "contents": "[Abrikossof's tumor of a toe]. A case of Abrikossof tumor in a 33 year old patient presenting a progressive growth of a toe without associated pain or inflamation. There was an important hypertrophy of the affected toe with hyperkeratosis and pseudoelephantiasis. The histologic examination showed a massive infiltration of granular cells in the dermis. The exceptional localisation of the tumor in this case is emphasized."}
{"id": "PMID:185474", "title": "[Multiple glomangiomas].", "content": "A case of multiple glomangioma in a 25 year old male patient is reported. The lesions started in an eruptive way affecting the upper limbs and trunk. Most of the forty lesions were painless but the larger ones were painful on pressure. Pain was not elicited by cold nor increased venous pressure. The histopathological examination of three lesions revealed a noncapsulated, angiomatous type of glomus tumor with a small number of glomus cells. Sweat glands are often imprisoned by the tumor in the deep dermis. The classification of glomangioma in solitary, multiple regional and disseminated types is discussed and their clinicopathological features are reviewed. The relationships and differential diagnosis with blue-rubber-bleb-naevus and post-traumatic angiomatosis are discussed.", "contents": "[Multiple glomangiomas]. A case of multiple glomangioma in a 25 year old male patient is reported. The lesions started in an eruptive way affecting the upper limbs and trunk. Most of the forty lesions were painless but the larger ones were painful on pressure. Pain was not elicited by cold nor increased venous pressure. The histopathological examination of three lesions revealed a noncapsulated, angiomatous type of glomus tumor with a small number of glomus cells. Sweat glands are often imprisoned by the tumor in the deep dermis. The classification of glomangioma in solitary, multiple regional and disseminated types is discussed and their clinicopathological features are reviewed. The relationships and differential diagnosis with blue-rubber-bleb-naevus and post-traumatic angiomatosis are discussed."}
{"id": "PMID:185476", "title": "[Prognostic value of histological rare breast cancer (author's transl)].", "content": "Among 835 cases of female breast cancer in the years 1951-1971 we found 44 histological rare cancer (comedo-carcinoma 21, carcinoma cribosum 1, gelatinous carcinoma 8, squamous cell carcinoma 3, mixed carcinoma 11). In agreement with the literature we are able to underline the favourable prognosis of the slow growing forms of the neoplasms like gelatinous carcinoma, comedo-carcinoma and carcinoma cribrosum opposite to squamous cell carcinoma and mixed carcinoma.", "contents": "[Prognostic value of histological rare breast cancer (author's transl)]. Among 835 cases of female breast cancer in the years 1951-1971 we found 44 histological rare cancer (comedo-carcinoma 21, carcinoma cribosum 1, gelatinous carcinoma 8, squamous cell carcinoma 3, mixed carcinoma 11). In agreement with the literature we are able to underline the favourable prognosis of the slow growing forms of the neoplasms like gelatinous carcinoma, comedo-carcinoma and carcinoma cribrosum opposite to squamous cell carcinoma and mixed carcinoma."}
{"id": "PMID:185477", "title": "Glomus jugulare tumors of the middle ear and mastoid: diagnosis and surgical treatment.", "content": "At the 1976 Southern Sectional Meeting of American Laryngological, Rhinological and Otological Society, Inc., a color movie presenting two cases on the \"diagnosis and treatment of glomus jugulare tumors of the middle ear and mastoid\" was shown. The purpose of this paper and film is to describe the author's experience of 16 cases of glomus tumors involving the middle ear and mastoid (seven tympanicum and nine jugulare). A review of the literature and findings pertaining specifically to the two cases shown in the film is presented.", "contents": "Glomus jugulare tumors of the middle ear and mastoid: diagnosis and surgical treatment. At the 1976 Southern Sectional Meeting of American Laryngological, Rhinological and Otological Society, Inc., a color movie presenting two cases on the \"diagnosis and treatment of glomus jugulare tumors of the middle ear and mastoid\" was shown. The purpose of this paper and film is to describe the author's experience of 16 cases of glomus tumors involving the middle ear and mastoid (seven tympanicum and nine jugulare). A review of the literature and findings pertaining specifically to the two cases shown in the film is presented."}
{"id": "PMID:185479", "title": "Relationships between skeletal maturity and submaximal working capacity in boys 8 to 18 years.", "content": "Skeletal age (SA) height, weight, PWC130, Vo2 at 130 heart rate (Vo130) and cardiorespiratory adaptation to work at 3 kgm-sec-1 were measured in 237 boys ranging in age from 8 to 18 years. Correlations for the total population for the variables of the study are generally higher with SA than with chronological age (CA), although there is no significant difference between the two sets of correlations. Analysis of linear trend indicate that significant nonlinear components are more frequent in the relationships between the variables and SA than with CA.Multiple regression analyses for each variate as dependent variable indicate that height and body weight generally contribute more to the explained variance, while SA is the next best predictor. CA is the least significant of the four independent variables. The total variance explained between any of the submaximal working capacity related measures acting as dependent variable and CA, height and weight is not significantly affected by the presence or absence of SA. The present study thus indicates that SA is not a significant factor in explaining submaximal working capacity, beyond CA, height and weight, when considered over the 8 to 18 year age span. However, when considering shorter age spans, or when considering the adolescent period (12-16 years), SA correlates better with PWC130 (.320 less than r less than .675) and with Vo130 (.299 less than r less than .772).", "contents": "Relationships between skeletal maturity and submaximal working capacity in boys 8 to 18 years. Skeletal age (SA) height, weight, PWC130, Vo2 at 130 heart rate (Vo130) and cardiorespiratory adaptation to work at 3 kgm-sec-1 were measured in 237 boys ranging in age from 8 to 18 years. Correlations for the total population for the variables of the study are generally higher with SA than with chronological age (CA), although there is no significant difference between the two sets of correlations. Analysis of linear trend indicate that significant nonlinear components are more frequent in the relationships between the variables and SA than with CA.Multiple regression analyses for each variate as dependent variable indicate that height and body weight generally contribute more to the explained variance, while SA is the next best predictor. CA is the least significant of the four independent variables. The total variance explained between any of the submaximal working capacity related measures acting as dependent variable and CA, height and weight is not significantly affected by the presence or absence of SA. The present study thus indicates that SA is not a significant factor in explaining submaximal working capacity, beyond CA, height and weight, when considered over the 8 to 18 year age span. However, when considering shorter age spans, or when considering the adolescent period (12-16 years), SA correlates better with PWC130 (.320 less than r less than .675) and with Vo130 (.299 less than r less than .772)."}
{"id": "PMID:185483", "title": "Is decreased activity of C-II activated lipoprotein lipase in type III hyperlipoproteinemia (broad-beta-disease) a cause or an effect of increased apolipoprotein E levels?", "content": "Apolipoprotein E (ApoE; \"arginine-rich\" polypeptide) strongly inhibited both C-I and C-II activated lipoprotein lipases but not the protamine insensitive triglyceride lipase. Inhibition of lipoprotein lipases by ApoE in contrast to inhibition by C-III was not reversed to any significant extent by either increased concentration of activator or triglyceride in the substrate. Our previous studies have shown that in a type III hyperlipoproteinemia (broad-beta-disease) a post-heparin plasma lipoprotein lipase activated by C-II polypeptide of lipoprotein C is decreased in enzyme activity and exhibits an impaired ability to hydrolyze triglycerides in very low density lipoproteins. Type III patients are characterized by elevated concentrations of ApoE in the serum. The data presented in this report suggest that the decreased C-II activated lipoprotein lipase may be further aggravated by increased ApoE levels. Since this enzyme is involved in the catabolism and removal of lipoproteins, decreased activity of C-II activativated lipoprotein lipase may presumably be responsible for increased ApoE.", "contents": "Is decreased activity of C-II activated lipoprotein lipase in type III hyperlipoproteinemia (broad-beta-disease) a cause or an effect of increased apolipoprotein E levels? Apolipoprotein E (ApoE; \"arginine-rich\" polypeptide) strongly inhibited both C-I and C-II activated lipoprotein lipases but not the protamine insensitive triglyceride lipase. Inhibition of lipoprotein lipases by ApoE in contrast to inhibition by C-III was not reversed to any significant extent by either increased concentration of activator or triglyceride in the substrate. Our previous studies have shown that in a type III hyperlipoproteinemia (broad-beta-disease) a post-heparin plasma lipoprotein lipase activated by C-II polypeptide of lipoprotein C is decreased in enzyme activity and exhibits an impaired ability to hydrolyze triglycerides in very low density lipoproteins. Type III patients are characterized by elevated concentrations of ApoE in the serum. The data presented in this report suggest that the decreased C-II activated lipoprotein lipase may be further aggravated by increased ApoE levels. Since this enzyme is involved in the catabolism and removal of lipoproteins, decreased activity of C-II activativated lipoprotein lipase may presumably be responsible for increased ApoE."}
{"id": "PMID:185484", "title": "Inhibition of actions of glucagon in adipocytes by gastric inhibitory polypeptide.", "content": "Possible interactions between gastric inhibitory polypeptide (GIP) and glucagon were investigated in rat adipocytes. GIP was nonlipolytic and inhibited lipolysis stimulated by glucagon but not that stimulated by secretin or vasoactive intestinal polypeptide (VIP). GIP competed with 125I-glucagon for binding to adipocyte receptors, and at physiologic concentrations inhibited the stimulation of AMP produced by glucagon. Thus GIP acts as an inhibitor of actions of glucagon on adipocytes and may be a physiologic modulator of effects of glucagon.", "contents": "Inhibition of actions of glucagon in adipocytes by gastric inhibitory polypeptide. Possible interactions between gastric inhibitory polypeptide (GIP) and glucagon were investigated in rat adipocytes. GIP was nonlipolytic and inhibited lipolysis stimulated by glucagon but not that stimulated by secretin or vasoactive intestinal polypeptide (VIP). GIP competed with 125I-glucagon for binding to adipocyte receptors, and at physiologic concentrations inhibited the stimulation of AMP produced by glucagon. Thus GIP acts as an inhibitor of actions of glucagon on adipocytes and may be a physiologic modulator of effects of glucagon."}
{"id": "PMID:185485", "title": "Demonstration of the production of human thyroid-stimulating immunoglobulins (HTSI) by Graves' lymphocytes cultured in vitro with phytohaemagglutinin (PHA).", "content": "The lymphocytes from patients with Graves' disease or from healthy subjects have been cultured in vitro either alone or with phytohemagglutinin (PHA). After six days the culture supernatants have been assayed for their human thyroid-stimulating activity by measuring increases in adenosine 3',5' monophosphate (cyclic AMP) in human thyroid slices with which the supernatants have been incubated. Significant levels of human thyroid stimulator activity were found in the culture in which Graves' lymphocytes were cultured with PHA. This activity has been abolished by precipitation of the IgG from the culture supernatant with goat antihuman IgG serum. In contrast, when Graves' lymphocytes were cultured alone, or when control lymphocytes were cultured either alone or with PHA, there was no overall significant production of human thyroid-stimulating immunoglobulin (HTSI). It is concluded that Graves' lymphocytes can be stimulated by PHA to produce HTSI in vitro. Since PHA is known to stimulate only the T lymphocytes, which do not themselves elaborate immunoglobulins as the B lymphocytes do, the above observations indicate a cooperation between T and B lymphocytes in the production of HTSI, at least in this system.", "contents": "Demonstration of the production of human thyroid-stimulating immunoglobulins (HTSI) by Graves' lymphocytes cultured in vitro with phytohaemagglutinin (PHA). The lymphocytes from patients with Graves' disease or from healthy subjects have been cultured in vitro either alone or with phytohemagglutinin (PHA). After six days the culture supernatants have been assayed for their human thyroid-stimulating activity by measuring increases in adenosine 3',5' monophosphate (cyclic AMP) in human thyroid slices with which the supernatants have been incubated. Significant levels of human thyroid stimulator activity were found in the culture in which Graves' lymphocytes were cultured with PHA. This activity has been abolished by precipitation of the IgG from the culture supernatant with goat antihuman IgG serum. In contrast, when Graves' lymphocytes were cultured alone, or when control lymphocytes were cultured either alone or with PHA, there was no overall significant production of human thyroid-stimulating immunoglobulin (HTSI). It is concluded that Graves' lymphocytes can be stimulated by PHA to produce HTSI in vitro. Since PHA is known to stimulate only the T lymphocytes, which do not themselves elaborate immunoglobulins as the B lymphocytes do, the above observations indicate a cooperation between T and B lymphocytes in the production of HTSI, at least in this system."}
{"id": "PMID:185486", "title": "Chylomicron clearance in normal and hyperlipidemic man.", "content": "A method has been developed for measurement of fractional clearance rates of chylomicrons in man. The technique employs constant infusion of emulsified fat into the duodenum at a rate of 200 mg/kh/hr. After 5 hr of infusion, concentrations of triglycerides (TG) in the chylomicron fraction become constant for the subsequent 5 hr. Since the input of chylomicron-TG is known, fractional removal rates can be calculated from steady-state plasma levels. In 21 patients with normal TG levels, clearance rates for chylomicrons were extremely rapid (t1/2 for chylomicron-TG equals 4.5 +/- 2.9 (SD) min). In 30 patients with endogenous hypertriglyceridemia, clearance was generally prolonged (t1/2 equals 23 +/- 5.5 min). This delay in chylomicron clearance could have been due either to a defect in removal of all TG-rich lipoproteinarticles; a generalized defect in clearance capacity for plasma TG was apparently ruled out for most patients by the further observation that reduction of endogenous TG by caloric restriction caused chylomicron removal to return to normal. These studies also showed that endogenous-TG is removed much less efficiently than chylomicron-TG, and in some patients, this discrepancy is particularly marked.", "contents": "Chylomicron clearance in normal and hyperlipidemic man. A method has been developed for measurement of fractional clearance rates of chylomicrons in man. The technique employs constant infusion of emulsified fat into the duodenum at a rate of 200 mg/kh/hr. After 5 hr of infusion, concentrations of triglycerides (TG) in the chylomicron fraction become constant for the subsequent 5 hr. Since the input of chylomicron-TG is known, fractional removal rates can be calculated from steady-state plasma levels. In 21 patients with normal TG levels, clearance rates for chylomicrons were extremely rapid (t1/2 for chylomicron-TG equals 4.5 +/- 2.9 (SD) min). In 30 patients with endogenous hypertriglyceridemia, clearance was generally prolonged (t1/2 equals 23 +/- 5.5 min). This delay in chylomicron clearance could have been due either to a defect in removal of all TG-rich lipoproteinarticles; a generalized defect in clearance capacity for plasma TG was apparently ruled out for most patients by the further observation that reduction of endogenous TG by caloric restriction caused chylomicron removal to return to normal. These studies also showed that endogenous-TG is removed much less efficiently than chylomicron-TG, and in some patients, this discrepancy is particularly marked."}
{"id": "PMID:185487", "title": "The distribution of plasma lipoproteins in middle-aged male runners.", "content": "Stimulated by increasing evidence of an inverse relationship between plasma high-density lipoprotein cholesterol level and frequency of coronary heart disease, we determined concentrations of fasting plasma cholesterol, triglyceride, and lipoproteins in 41 very active men (running greater than 15 miles/wk for the previous year) 35-59 years of age (mean age, 47) and in a comparison group of men of similar age, randomly selected from three northern California communities. The runners had significantly (p less than 0.05) decreased mean plasma triglyceride (70 versus 146 mg/100 ml), total plasma cholesterol (200 versus 210 mg/100 ml), and low-density lipoprotein (LDL) cholesterol (125 versus 139 mg/100 ml) concentrations, and a higher mean level of high-density lipoprotein (HDL) cholesterol (64 versus 43 mg/100 ml) than the comparison group (n equals 147 for HDL and LDL; n equals 743 for total cholesterol and triglycerides). These very active men exhibited a plasma lipoprotein profile resembling that of younger women rather tan of sedentary, middle-aged men. This characteristic, and apparently advantageous, pattern could be only partially accounted for by differences in adiposity between runners and control subjects.", "contents": "The distribution of plasma lipoproteins in middle-aged male runners. Stimulated by increasing evidence of an inverse relationship between plasma high-density lipoprotein cholesterol level and frequency of coronary heart disease, we determined concentrations of fasting plasma cholesterol, triglyceride, and lipoproteins in 41 very active men (running greater than 15 miles/wk for the previous year) 35-59 years of age (mean age, 47) and in a comparison group of men of similar age, randomly selected from three northern California communities. The runners had significantly (p less than 0.05) decreased mean plasma triglyceride (70 versus 146 mg/100 ml), total plasma cholesterol (200 versus 210 mg/100 ml), and low-density lipoprotein (LDL) cholesterol (125 versus 139 mg/100 ml) concentrations, and a higher mean level of high-density lipoprotein (HDL) cholesterol (64 versus 43 mg/100 ml) than the comparison group (n equals 147 for HDL and LDL; n equals 743 for total cholesterol and triglycerides). These very active men exhibited a plasma lipoprotein profile resembling that of younger women rather tan of sedentary, middle-aged men. This characteristic, and apparently advantageous, pattern could be only partially accounted for by differences in adiposity between runners and control subjects."}
{"id": "PMID:185488", "title": "Changes in plasma triglyceride metabolism during withdrawal of bile.", "content": "The relationship between bile acid turnover and plasma triglyceride metabolism was examined in a group of seven moderately overweight and hypertriglyceridemic men. Bile acid synthesis was stimulated by the continuous aspiration of duodenal contents so that 150% of the bile acid pool was removed in 18 hr. In comparison with the average concentration of very low density lipoprotein triglyceride (VLDL-TG) during a preceding 8-10 hr control period, bile withdrawal led to an increase in VLDL-TG of 34%, 43%, 32%, 14%, 26%, 14%, and 8% (mean +24%) in the seven men. In control studies performed on another day the mean change over a similar period of time, but without bile withdrawal, was +1% (p less than 0.01). The kinetics of VLDL triglyceride were studied in some of the subjects by analyzing the triglyceride specific radioactivity curves following injections of radiolabelled glycerol. In control studies of 26 hr duration the curves were resolved into two apparent exponential functions, the second part of the curve appearing between 15 and 18 hr after pulse-labeling. During bile withdrawal, the second apparent exponential developed sooner, within 4 hr of beginning the aspiration and coincided with the rise in triglyceride concentration. The fractional rate of the second exponential was at least as fast during bile withdrawal as during the control period despite the increase in VLDL-TG pool size, suggesting that the turnover of triglyceride was higher at a time when bile acid production was being stimulated.", "contents": "Changes in plasma triglyceride metabolism during withdrawal of bile. The relationship between bile acid turnover and plasma triglyceride metabolism was examined in a group of seven moderately overweight and hypertriglyceridemic men. Bile acid synthesis was stimulated by the continuous aspiration of duodenal contents so that 150% of the bile acid pool was removed in 18 hr. In comparison with the average concentration of very low density lipoprotein triglyceride (VLDL-TG) during a preceding 8-10 hr control period, bile withdrawal led to an increase in VLDL-TG of 34%, 43%, 32%, 14%, 26%, 14%, and 8% (mean +24%) in the seven men. In control studies performed on another day the mean change over a similar period of time, but without bile withdrawal, was +1% (p less than 0.01). The kinetics of VLDL triglyceride were studied in some of the subjects by analyzing the triglyceride specific radioactivity curves following injections of radiolabelled glycerol. In control studies of 26 hr duration the curves were resolved into two apparent exponential functions, the second part of the curve appearing between 15 and 18 hr after pulse-labeling. During bile withdrawal, the second apparent exponential developed sooner, within 4 hr of beginning the aspiration and coincided with the rise in triglyceride concentration. The fractional rate of the second exponential was at least as fast during bile withdrawal as during the control period despite the increase in VLDL-TG pool size, suggesting that the turnover of triglyceride was higher at a time when bile acid production was being stimulated."}
{"id": "PMID:185489", "title": "Pediatric familial type III hyperlipoproteinemia.", "content": "Familial type III hyperlipoproteinemia is almost always first diagnosed in adults; the two 16-yr-old probands with type III in this report represent only the fifth and sixth children reported with the disorder. S.E., a 16-yr-old female, and C.H., a 21-yr-old male, (with palmar xanthomas at age 16) had beta-migrating abnormal very low density lipoproteins (beta-VLDL), density less than 1.006. S.E.'s brother (age 21) and mother (age 57) had type III; her grandmother had beta-VLDL and elevated triglycerides, and a maternal uncle had type IV hyperlipoproteinemia. C.H.'s father had type III; a sister and paternal aunt had type IV hyperlipoproteinemia. It is important to consider the diagnosis of type III hyperlipoproteinemia in the pediatric age group, particularly in children from families with type III hyperlipoproteinemia.", "contents": "Pediatric familial type III hyperlipoproteinemia. Familial type III hyperlipoproteinemia is almost always first diagnosed in adults; the two 16-yr-old probands with type III in this report represent only the fifth and sixth children reported with the disorder. S.E., a 16-yr-old female, and C.H., a 21-yr-old male, (with palmar xanthomas at age 16) had beta-migrating abnormal very low density lipoproteins (beta-VLDL), density less than 1.006. S.E.'s brother (age 21) and mother (age 57) had type III; her grandmother had beta-VLDL and elevated triglycerides, and a maternal uncle had type IV hyperlipoproteinemia. C.H.'s father had type III; a sister and paternal aunt had type IV hyperlipoproteinemia. It is important to consider the diagnosis of type III hyperlipoproteinemia in the pediatric age group, particularly in children from families with type III hyperlipoproteinemia."}
{"id": "PMID:185493", "title": "Studies on the role of cAMP-dependent protein kinase in the actions of glucagon and catecholamines on liver glycogen metabolism.", "content": "Glucagon causes a rapid activation of cAMP-dependent protein kinase in rat liver parenchymal cells which correlates well with the accumulation of cAMP. Full activation of phosphorylase or inactivation of glycogen synthase is achieved with half-maximal or less activation of protein kinase. Epinephrine stimulates glycogen breakdown in these cells mainly by mechanisms involving alpha-adrenergic receptors and not beta-receptors. Activition of alpha-receptors results in rapid activation of phosphorylase and inactivation of glycogen synthase without accumulation of cAMP or activation of cAMP-dependent protein kinase. Activation of beta-receptors causes a transient rise in cAMP and a short-lived activation of protein kinase with correspondingly little stimulation of glycogenolysis.", "contents": "Studies on the role of cAMP-dependent protein kinase in the actions of glucagon and catecholamines on liver glycogen metabolism. Glucagon causes a rapid activation of cAMP-dependent protein kinase in rat liver parenchymal cells which correlates well with the accumulation of cAMP. Full activation of phosphorylase or inactivation of glycogen synthase is achieved with half-maximal or less activation of protein kinase. Epinephrine stimulates glycogen breakdown in these cells mainly by mechanisms involving alpha-adrenergic receptors and not beta-receptors. Activition of alpha-receptors results in rapid activation of phosphorylase and inactivation of glycogen synthase without accumulation of cAMP or activation of cAMP-dependent protein kinase. Activation of beta-receptors causes a transient rise in cAMP and a short-lived activation of protein kinase with correspondingly little stimulation of glycogenolysis."}
{"id": "PMID:185498", "title": "Effect of actinomycin D on plaque formation by mengovirus.", "content": "Treatment of L cell monolayers with actinomycin D resulted in an increase in both the size and number of mengovirus plaques when compared to untreated cells. Addition of the drug to the agar overlay was as effective as pretreatment provided the addition was immediately after virus adsorption. The increased plaque number observed was apparently not due to rescue of defective particles or inhibition of interferon production. The data indicate that more mengovirus particles can successfully complete the infectious cycle in L cells in the presence of actinomycin. The data also suggest that indigenous C-type particles in L cells may interfere with picornavirus replication.", "contents": "Effect of actinomycin D on plaque formation by mengovirus. Treatment of L cell monolayers with actinomycin D resulted in an increase in both the size and number of mengovirus plaques when compared to untreated cells. Addition of the drug to the agar overlay was as effective as pretreatment provided the addition was immediately after virus adsorption. The increased plaque number observed was apparently not due to rescue of defective particles or inhibition of interferon production. The data indicate that more mengovirus particles can successfully complete the infectious cycle in L cells in the presence of actinomycin. The data also suggest that indigenous C-type particles in L cells may interfere with picornavirus replication."}
{"id": "PMID:185501", "title": "Fatal cadmium-fume pneumonitis.", "content": "A 38-year-old man developed acute respiratory distress several hours after welding cadmium-plated drums without taking precautions against the inhalation of fumes. His respiratory distress worsened over the ensuing three and a half days, and he died. Histological examination of the lungs showed changes of acute cadmium-fume pneumonitis, and chemical analysis of lungs and liver provided confirmatory evidence of considerable absorption of cadmium, of the order previously recorded as causing death. This case is reported so as to renew awareness of this condition, as the cause of the illness was not diagnosed during life.", "contents": "Fatal cadmium-fume pneumonitis. A 38-year-old man developed acute respiratory distress several hours after welding cadmium-plated drums without taking precautions against the inhalation of fumes. His respiratory distress worsened over the ensuing three and a half days, and he died. Histological examination of the lungs showed changes of acute cadmium-fume pneumonitis, and chemical analysis of lungs and liver provided confirmatory evidence of considerable absorption of cadmium, of the order previously recorded as causing death. This case is reported so as to renew awareness of this condition, as the cause of the illness was not diagnosed during life."}
{"id": "PMID:185500", "title": "[Localization of energy generators in methane oxidizing bacteria].", "content": "Cytochromes a, b and c, and their quantitative distribution in the cells, were studied by means of differential spectra in obligate methane oxidizing bacteria, Methylosinus trichosporium with the serine pathway of methane carbon assimilation and Methylomonas agile with the ribulose phosphate pathway of methane carbon assimilation, and different types of topography of intracytoplasmic membranes. The membranes are involved in processes of coupled respiration which was confirmed by cytochemical reactions employed for studying the terminal step of the electron transport chain and Mg2+-stimulated ATPase.", "contents": "[Localization of energy generators in methane oxidizing bacteria]. Cytochromes a, b and c, and their quantitative distribution in the cells, were studied by means of differential spectra in obligate methane oxidizing bacteria, Methylosinus trichosporium with the serine pathway of methane carbon assimilation and Methylomonas agile with the ribulose phosphate pathway of methane carbon assimilation, and different types of topography of intracytoplasmic membranes. The membranes are involved in processes of coupled respiration which was confirmed by cytochemical reactions employed for studying the terminal step of the electron transport chain and Mg2+-stimulated ATPase."}
{"id": "PMID:185504", "title": "[The effect of etiroxate on serum lipids after myocardial infarction or in angina pectoris].", "content": "The lipid-lowering effect of etiroxate was studied in a double-blind cross-over trial comprising 183 patients with hyperlipoproteinaemia, most of whom had suffered myocardial infarction or exhibited confirmed coronary insufficiency. Etiroxate (40 mg daily) and placebo were administered for a period of 12 weeks each. In approximately 60% of the cases with Type IIa/IIb hyperlipoproteinaemia the cholesterol level fell by more than 10%. As regards the frequency of heart complaints, the consumption of nitroglycerine capsules, and heart rate, there were no statistically significant differences between the placebo and etiroxate phases. Thus etiroxate did not have any unfavourable cardiac side-effects in the patients of this study. No negative effects on hepatic and renal function or the peripheral blood count were observed.", "contents": "[The effect of etiroxate on serum lipids after myocardial infarction or in angina pectoris]. The lipid-lowering effect of etiroxate was studied in a double-blind cross-over trial comprising 183 patients with hyperlipoproteinaemia, most of whom had suffered myocardial infarction or exhibited confirmed coronary insufficiency. Etiroxate (40 mg daily) and placebo were administered for a period of 12 weeks each. In approximately 60% of the cases with Type IIa/IIb hyperlipoproteinaemia the cholesterol level fell by more than 10%. As regards the frequency of heart complaints, the consumption of nitroglycerine capsules, and heart rate, there were no statistically significant differences between the placebo and etiroxate phases. Thus etiroxate did not have any unfavourable cardiac side-effects in the patients of this study. No negative effects on hepatic and renal function or the peripheral blood count were observed."}
{"id": "PMID:185505", "title": "[Lymphoblastomic sarcoma of the Burkitt type (the so-called \"white Burkitt tumor\") (author's transl)].", "content": "We report about a lymphoblastomic sarcoma of the Burkitt type with a seventeen year old young man. The Burkitt lymphoma occupies a special position among the malignant tumours and occurs rarely in temperate zones. From the clinical and histological point of view, we found the typical image of a unilocular Burkitt tumor. It was not possible to verify an elevated titre of antibodies against the Epstein-Barr virus.", "contents": "[Lymphoblastomic sarcoma of the Burkitt type (the so-called \"white Burkitt tumor\") (author's transl)]. We report about a lymphoblastomic sarcoma of the Burkitt type with a seventeen year old young man. The Burkitt lymphoma occupies a special position among the malignant tumours and occurs rarely in temperate zones. From the clinical and histological point of view, we found the typical image of a unilocular Burkitt tumor. It was not possible to verify an elevated titre of antibodies against the Epstein-Barr virus."}
{"id": "PMID:185506", "title": "[Group Y meningococci as respiratory pathogens (author's transl)].", "content": "Serogroup Y meningococci are more frequently respiratory pathogens than one might suppose from their prevalence in meningitis and septicemia. A case of a peracute fatal septicemia caused by group Y meningococci is reported here in which post mortem hemorrhagic lesions of the pharyngeal, laryngeal and tracheal mucosae as well as a beginning pneumonia and pleurisy have been found. The association of meningococcal and respiratory viral infections is discussed.", "contents": "[Group Y meningococci as respiratory pathogens (author's transl)]. Serogroup Y meningococci are more frequently respiratory pathogens than one might suppose from their prevalence in meningitis and septicemia. A case of a peracute fatal septicemia caused by group Y meningococci is reported here in which post mortem hemorrhagic lesions of the pharyngeal, laryngeal and tracheal mucosae as well as a beginning pneumonia and pleurisy have been found. The association of meningococcal and respiratory viral infections is discussed."}
{"id": "PMID:185508", "title": "SV40 DNA sequences as an example of the structure of genes functioning in animal cell nuclei.", "content": "Recent studies of the structure of messenger RNA have demonstrated the existence of untranslated sequences of the 3' and 5' end of the messages. In addition analysis of transcription in vitro has indicated that the nucleotide sequence U6 purine may be part of a transcription termination signal in prokaryotes. Recently it has been possible to determine the sequence of extensive portions of the DNA of SV40 virus. This article reviews the analogies between certain of these sequences and sequences available from prokaryotic messengers and DNAs. Unusual structures, including blocks of AT-rich and GC-rich segment sections and symmetric regions in the DNA near the origin of DNA replication, have been demonstrated and the distribution of stretches of 6 or more deoxyadenylic acids in the DNA of SV40 is consistent with some rho for these sequences in animal cells, either as terminators of transcription or as sites where degradation of transcripts is initiated or sites related to the selective rejection or degradation of transcipts.", "contents": "SV40 DNA sequences as an example of the structure of genes functioning in animal cell nuclei. Recent studies of the structure of messenger RNA have demonstrated the existence of untranslated sequences of the 3' and 5' end of the messages. In addition analysis of transcription in vitro has indicated that the nucleotide sequence U6 purine may be part of a transcription termination signal in prokaryotes. Recently it has been possible to determine the sequence of extensive portions of the DNA of SV40 virus. This article reviews the analogies between certain of these sequences and sequences available from prokaryotic messengers and DNAs. Unusual structures, including blocks of AT-rich and GC-rich segment sections and symmetric regions in the DNA near the origin of DNA replication, have been demonstrated and the distribution of stretches of 6 or more deoxyadenylic acids in the DNA of SV40 is consistent with some rho for these sequences in animal cells, either as terminators of transcription or as sites where degradation of transcripts is initiated or sites related to the selective rejection or degradation of transcipts."}
{"id": "PMID:185509", "title": "Poly ADP-ribosylation of DNA-dependent RNA polymerase I from quail oviduct. Dependence on progesterone stimulation.", "content": "Progesterone causes in goblet cells of oviducts of estrogen hormone-stimulated immature quails selectively gene activation without affecting DNA synthesis. This biological model has been used to study the influence of poly ADP-ribosylation during the processes of DNA transcription. Administration of progesterone in vivo causes an increase of the activity of RNA polymerase I and II in isolated nuclei. This increase is accompanied by a marked decrease of the specific activity of poly (ADP-Rib) polymerase. After in vitro ADP-ribosylation of nuclear proteins the template capacity of chromatin for \"\"exogenous'' RNA synthesis (with E. coli DNA-dependent RNA polymerases) as well as for \"\"endogenous'' RNA synthesis with DNA dependent RNA polymerases II is not affected, whereas the data presented seem to indicate that the capacity for RNA synthesis mediated by \"\"endogenous'' DNA-dependent RNA polymerase I might be inhibited after ADP-ribosylation. Evidence is presented to show that a considerable amount of poly (ADP-Rib), synthesized by poly (ADP-Rib) polymerase in isolated nuclei, is linked with RNA polymerase I. The rate of synthesis of poly (ADP-Rib) is dependent on the incubation temperature (optimum at 25 degrees C) and it can be inhibited by the specific inhibitors of poly (ADP-Rib) polymerase nicotineamide, thymidine and formycin B. Poly (ADP-Rib) is probably associated with RNA polymerase I through a covalent linkage. ADP-ribosylated RNA polymerase I has been purified 550 fold with respect to the nuclear extract corresponding to a 4,000 fold purification from the whole cell homogenate. The ratio between poly (ADP-Rib), formed during preincubation of nuclei with NAD, and RNA polymerase I remains almost constant during the purification procedures. The extent of ADP-ribosylation of RNA polymerase I decreases during gene expression. Thus we conclude that poly ADP-ribosylation of this enzyme is one of the regulatory mechanisms by which specificity of DNA transcription is achieved.", "contents": "Poly ADP-ribosylation of DNA-dependent RNA polymerase I from quail oviduct. Dependence on progesterone stimulation. Progesterone causes in goblet cells of oviducts of estrogen hormone-stimulated immature quails selectively gene activation without affecting DNA synthesis. This biological model has been used to study the influence of poly ADP-ribosylation during the processes of DNA transcription. Administration of progesterone in vivo causes an increase of the activity of RNA polymerase I and II in isolated nuclei. This increase is accompanied by a marked decrease of the specific activity of poly (ADP-Rib) polymerase. After in vitro ADP-ribosylation of nuclear proteins the template capacity of chromatin for \"\"exogenous'' RNA synthesis (with E. coli DNA-dependent RNA polymerases) as well as for \"\"endogenous'' RNA synthesis with DNA dependent RNA polymerases II is not affected, whereas the data presented seem to indicate that the capacity for RNA synthesis mediated by \"\"endogenous'' DNA-dependent RNA polymerase I might be inhibited after ADP-ribosylation. Evidence is presented to show that a considerable amount of poly (ADP-Rib), synthesized by poly (ADP-Rib) polymerase in isolated nuclei, is linked with RNA polymerase I. The rate of synthesis of poly (ADP-Rib) is dependent on the incubation temperature (optimum at 25 degrees C) and it can be inhibited by the specific inhibitors of poly (ADP-Rib) polymerase nicotineamide, thymidine and formycin B. Poly (ADP-Rib) is probably associated with RNA polymerase I through a covalent linkage. ADP-ribosylated RNA polymerase I has been purified 550 fold with respect to the nuclear extract corresponding to a 4,000 fold purification from the whole cell homogenate. The ratio between poly (ADP-Rib), formed during preincubation of nuclei with NAD, and RNA polymerase I remains almost constant during the purification procedures. The extent of ADP-ribosylation of RNA polymerase I decreases during gene expression. Thus we conclude that poly ADP-ribosylation of this enzyme is one of the regulatory mechanisms by which specificity of DNA transcription is achieved."}
{"id": "PMID:185510", "title": "Integration of biochemical functions of different cells of rat gastric mucosa for hydrochloric acid secretion.", "content": "The regulation patterns of gastric acid secretion in rats were investigated. Pentagastrin and histamine stimulate gastric acid secretion, but the inhibitors of DNA-dependent synthesis of RNA and of proteins prevent only the pentagastrin action. It has been found that pentagastrin induces histidine decarboxylase in gastric mucosa, ensuring local accumulation of histamine. The latter activates adenylate cyclase and results in 3',5'-AMP accumulation in gastric tissues. The administration of pentagastrin, histamine or 3',5'-AMP enhances the activity of gastric carbonic anhydrase, the enzyme which takes part in HCl formation. The data suggest that these three compounds act sequentially (pentagastrin leads to histamine leads to3',5'-AMP) and the effect of the last one could be mediated through 3',5'-AMP dependent protein kinase. The experiments in vitro demonstrated that gastric carbonic anhydrase can be separated into two isoenzymes and thephosphorylation of one of them by the 3',5'-AMP dependent protein kinase sharply increases its activity. The findings raise the possibility that histamine and 3',5'-AMP, mediating gastrin action, form together with enzymes (histidine decarboxylase, adenylate cyclase, protein kinase, carbonic anhydrase) a caascade of amplifiers. Autoradiographic studies have shown that [3H]-pentagastrin is not bound by oxyntic cells but adheres preferentially to histamine-producing alpha-like endocrine cells and to the chief cells, while 3H-histamine adheres preferentially to oxyntic and to chief cells. Electron microscopy indicates that only pentagastrin (but not histamine) initiates in alpha-like endocrine cells ultrastructural changes characteristic for induction. Pentagastrin, histamine and 3',5'-AMP administration produces in oxyntic cells ultrastructural changes typical for the secretion processes. These results lead to assumption that pentagastrin (gastrin) induces histidine decarboxylase in alpha-like endocrine cells of gastric glands. Histamine which is secreted enhances adenylate cyclase activity in the neighbouring oxyntic cells where 3',5'-AMP dependent protein kinase activates carbonic anhydrase by means of phosphorylation. These different cells form, probably, a multicellular functional unit for gastric acid secretion.", "contents": "Integration of biochemical functions of different cells of rat gastric mucosa for hydrochloric acid secretion. The regulation patterns of gastric acid secretion in rats were investigated. Pentagastrin and histamine stimulate gastric acid secretion, but the inhibitors of DNA-dependent synthesis of RNA and of proteins prevent only the pentagastrin action. It has been found that pentagastrin induces histidine decarboxylase in gastric mucosa, ensuring local accumulation of histamine. The latter activates adenylate cyclase and results in 3',5'-AMP accumulation in gastric tissues. The administration of pentagastrin, histamine or 3',5'-AMP enhances the activity of gastric carbonic anhydrase, the enzyme which takes part in HCl formation. The data suggest that these three compounds act sequentially (pentagastrin leads to histamine leads to3',5'-AMP) and the effect of the last one could be mediated through 3',5'-AMP dependent protein kinase. The experiments in vitro demonstrated that gastric carbonic anhydrase can be separated into two isoenzymes and thephosphorylation of one of them by the 3',5'-AMP dependent protein kinase sharply increases its activity. The findings raise the possibility that histamine and 3',5'-AMP, mediating gastrin action, form together with enzymes (histidine decarboxylase, adenylate cyclase, protein kinase, carbonic anhydrase) a caascade of amplifiers. Autoradiographic studies have shown that [3H]-pentagastrin is not bound by oxyntic cells but adheres preferentially to histamine-producing alpha-like endocrine cells and to the chief cells, while 3H-histamine adheres preferentially to oxyntic and to chief cells. Electron microscopy indicates that only pentagastrin (but not histamine) initiates in alpha-like endocrine cells ultrastructural changes characteristic for induction. Pentagastrin, histamine and 3',5'-AMP administration produces in oxyntic cells ultrastructural changes typical for the secretion processes. These results lead to assumption that pentagastrin (gastrin) induces histidine decarboxylase in alpha-like endocrine cells of gastric glands. Histamine which is secreted enhances adenylate cyclase activity in the neighbouring oxyntic cells where 3',5'-AMP dependent protein kinase activates carbonic anhydrase by means of phosphorylation. These different cells form, probably, a multicellular functional unit for gastric acid secretion."}
{"id": "PMID:185512", "title": "[Therapy of Childhood Asthma with Beclomethasone Dipropionate (author's transl)].", "content": "In addition to the usual mangement of asthma the introduction of Beclomethasone-dipropionate aerosol can be considered as a progress in the long-term treatment of asthma, because in most cases oral and parenteral application of corticosteroids is no longer necessary. According to the results of many authors the wellknown side effects of steriod therapy have so far not been observed. We report our experiences with Beclomethasone in the treatment of 19 chronically asthmatic children.", "contents": "[Therapy of Childhood Asthma with Beclomethasone Dipropionate (author's transl)]. In addition to the usual mangement of asthma the introduction of Beclomethasone-dipropionate aerosol can be considered as a progress in the long-term treatment of asthma, because in most cases oral and parenteral application of corticosteroids is no longer necessary. According to the results of many authors the wellknown side effects of steriod therapy have so far not been observed. We report our experiences with Beclomethasone in the treatment of 19 chronically asthmatic children."}
{"id": "PMID:185513", "title": "[Screening of newborns for inborn errors of galactose metabolism. Methods and results].", "content": "Three inborn errors of galactose metabolism as known today. Only two of them cause illness: the deficiencies of galactokinase and of galactose-l-phosphate uridyltransferase. Both can be detected through mass screening of newborns and are amenable to a simple and successful dietary treatment. Mass screening of newborns for disorders of galactose metabolism can be performed efficiently and inexpensively if it is incorporated in the general newborn screening program.", "contents": "[Screening of newborns for inborn errors of galactose metabolism. Methods and results]. Three inborn errors of galactose metabolism as known today. Only two of them cause illness: the deficiencies of galactokinase and of galactose-l-phosphate uridyltransferase. Both can be detected through mass screening of newborns and are amenable to a simple and successful dietary treatment. Mass screening of newborns for disorders of galactose metabolism can be performed efficiently and inexpensively if it is incorporated in the general newborn screening program."}
{"id": "PMID:185514", "title": "[Preternatural anus and its care (author's transl)].", "content": "The most careful surgical technique, the guiding principles of which are outlined, is a prerequisite for the subsequent possibilities for correct care of preternatural anus and for preventing otherwise unavoidable complications. Four different programs are available to us for care; truss pad, adhesive bag, irrigation therapy and the Erlanger magnetic closure. For prophylaxis of frequent hernias and prolapses, wearing a made-to-measure body binder is indispensable. Skin lesions, formerly feared concomitant symptoms, can now be prevented or eliminated as a result of the development of non-irritant adhesives, combinations with sterculia rings or adhesive plasters and differentiated skin care products. A more comprehensive organization of those with preternatural anus within the framework of the German Ilco and the establishment of preternatural anus clinics and therapists would be desirable.", "contents": "[Preternatural anus and its care (author's transl)]. The most careful surgical technique, the guiding principles of which are outlined, is a prerequisite for the subsequent possibilities for correct care of preternatural anus and for preventing otherwise unavoidable complications. Four different programs are available to us for care; truss pad, adhesive bag, irrigation therapy and the Erlanger magnetic closure. For prophylaxis of frequent hernias and prolapses, wearing a made-to-measure body binder is indispensable. Skin lesions, formerly feared concomitant symptoms, can now be prevented or eliminated as a result of the development of non-irritant adhesives, combinations with sterculia rings or adhesive plasters and differentiated skin care products. A more comprehensive organization of those with preternatural anus within the framework of the German Ilco and the establishment of preternatural anus clinics and therapists would be desirable."}
{"id": "PMID:185517", "title": "Interaction between serum factors and T lymphocytes in Hodgkin's disease. Use as a diagnostic test.", "content": "We studied the mechanism of defective binding of sheep erythrocytes to the surface of peripheral blood T lymphocytes (E-rosette-formation) in Hodgkin's disease. The decreased percentage of E-rosette-forming cells (range, 21 to 77 per cent) in 25 patients with Hodgkin's disease was reversed and returned to normal range (52 to 78 per cent) by prior incubation of the T lymphocytes in tissue-culture medium with 20 per cent fetal-calf serum for 18 to 24 hours. The percentage of E-rosette-forming cells was suppressed by additional incubation with serum from patients with Hodgkin's disease (range, 20 to 61 per cent) but not with serum from patients with other neoplasms or from normal subjects (range, 52 to 74 per cent). Only target T lymphocytes from patients with Hodgkin's disease were suppressed by Hodgkin-disease serum. The findings suggest that there is a specific interaction between serum factors and the surface of peripheral blood T lymphocytes in Hodgkin's disease.", "contents": "Interaction between serum factors and T lymphocytes in Hodgkin's disease. Use as a diagnostic test. We studied the mechanism of defective binding of sheep erythrocytes to the surface of peripheral blood T lymphocytes (E-rosette-formation) in Hodgkin's disease. The decreased percentage of E-rosette-forming cells (range, 21 to 77 per cent) in 25 patients with Hodgkin's disease was reversed and returned to normal range (52 to 78 per cent) by prior incubation of the T lymphocytes in tissue-culture medium with 20 per cent fetal-calf serum for 18 to 24 hours. The percentage of E-rosette-forming cells was suppressed by additional incubation with serum from patients with Hodgkin's disease (range, 20 to 61 per cent) but not with serum from patients with other neoplasms or from normal subjects (range, 52 to 74 per cent). Only target T lymphocytes from patients with Hodgkin's disease were suppressed by Hodgkin-disease serum. The findings suggest that there is a specific interaction between serum factors and the surface of peripheral blood T lymphocytes in Hodgkin's disease."}
{"id": "PMID:185529", "title": "Susceptibility of chickens to avian encephalomyelitis virus. IV. Behavior of the virus in laying hens.", "content": "Some laying hens 6 months of age were inoculated subcutaneously or orally with a chick embryo--adapted strain of avian encephalomyelitis virus and examined for propagation of the virus in the body. When inoculated subcutaneously, the virus appeared in liver, spleen, ovarian follicle, and muscle at the site of inoculation 1 day, in kidney and lumbar part of the spinal cord 3 days, in the pancreas 5 days, in heart, duodenum, and cervical part of the spinal cord 7 days, and in the brain 11 days after inoculation. After its appearance, it increased gradually in amount in liver, spleen, pancreas, muscle at the site of inoculation, and cervical and lumbar parts of the spinal cord, but remained at a low level in any other organ. When examined 14 days after inoculation and later, it was distributed mainly in the central nervous system. It was detected from 12 of 16 organs examined. The highest virus level in each organ was 10(2.6)/0.1 g in pancreas and lumbar part of the spinal cord, which were followed by muscle at the site of inoculation (10(2.0)/0.1 g), spleen (10(1.8)/0.1 g), cervical part of the spinal cord, heart, and liver in the order listed. When inoculated orally, the virus was found sporadically in spleen, pancreas, kidney, cecum, ovarian follicle, and lumbar part of the spinal cord. The virus level was low in these organs, of which pancreas, kidney, and lumbar part of the spinal cord showed the highest virus level, or 10(1.3)/0.1 g.", "contents": "Susceptibility of chickens to avian encephalomyelitis virus. IV. Behavior of the virus in laying hens. Some laying hens 6 months of age were inoculated subcutaneously or orally with a chick embryo--adapted strain of avian encephalomyelitis virus and examined for propagation of the virus in the body. When inoculated subcutaneously, the virus appeared in liver, spleen, ovarian follicle, and muscle at the site of inoculation 1 day, in kidney and lumbar part of the spinal cord 3 days, in the pancreas 5 days, in heart, duodenum, and cervical part of the spinal cord 7 days, and in the brain 11 days after inoculation. After its appearance, it increased gradually in amount in liver, spleen, pancreas, muscle at the site of inoculation, and cervical and lumbar parts of the spinal cord, but remained at a low level in any other organ. When examined 14 days after inoculation and later, it was distributed mainly in the central nervous system. It was detected from 12 of 16 organs examined. The highest virus level in each organ was 10(2.6)/0.1 g in pancreas and lumbar part of the spinal cord, which were followed by muscle at the site of inoculation (10(2.0)/0.1 g), spleen (10(1.8)/0.1 g), cervical part of the spinal cord, heart, and liver in the order listed. When inoculated orally, the virus was found sporadically in spleen, pancreas, kidney, cecum, ovarian follicle, and lumbar part of the spinal cord. The virus level was low in these organs, of which pancreas, kidney, and lumbar part of the spinal cord showed the highest virus level, or 10(1.3)/0.1 g."}
{"id": "PMID:185530", "title": "Susceptibility of chickens to avian encephalomyelitis virus. V. Behavior of a field strain in laying hens.", "content": "Some 12-month-old laying hens were inoculated orally or subcutaneously with 10(4.7) EID50 of a field strain of avian encephalomyelitis virus. They were examined for propagation of the virus in the body at regular intervals of time. When two hens were sacrificed daily in the group of oral inoculation, the virus was found in liver, pancreas, and esophagus in both hens 1 day, in brain, lumbar part of the spinal cord, heart, spleen, pharynx, larynx, glandular stomach, muscle, and blood in one of the two hens 1 day, and in various parts of the body 3 approximately 9 days after inoculation. After that, the virus was detected almost continually from the central nervous system and abdominal parenchymatous organs in nearly all the hens examined up to the end of the observation period, or 21 days after inoculation. Virus detection from the digestive tract and ovarian follicle, however, decreased in frequency and virus titer was reduced remarkably with the lapse of time after inoculation. When the largest amount of virus was determined in each organ, it was the largest, or 10(6.5) EID50/0.1 g, in the liver and about 10(5.0) EID50/0.1 g in spleen, pancreas, kidney, and ovarian follicle. There was little difference in virus propagation and its course between the group of subcutaneous inoculation and that of oral administration.", "contents": "Susceptibility of chickens to avian encephalomyelitis virus. V. Behavior of a field strain in laying hens. Some 12-month-old laying hens were inoculated orally or subcutaneously with 10(4.7) EID50 of a field strain of avian encephalomyelitis virus. They were examined for propagation of the virus in the body at regular intervals of time. When two hens were sacrificed daily in the group of oral inoculation, the virus was found in liver, pancreas, and esophagus in both hens 1 day, in brain, lumbar part of the spinal cord, heart, spleen, pharynx, larynx, glandular stomach, muscle, and blood in one of the two hens 1 day, and in various parts of the body 3 approximately 9 days after inoculation. After that, the virus was detected almost continually from the central nervous system and abdominal parenchymatous organs in nearly all the hens examined up to the end of the observation period, or 21 days after inoculation. Virus detection from the digestive tract and ovarian follicle, however, decreased in frequency and virus titer was reduced remarkably with the lapse of time after inoculation. When the largest amount of virus was determined in each organ, it was the largest, or 10(6.5) EID50/0.1 g, in the liver and about 10(5.0) EID50/0.1 g in spleen, pancreas, kidney, and ovarian follicle. There was little difference in virus propagation and its course between the group of subcutaneous inoculation and that of oral administration."}
{"id": "PMID:185531", "title": "Experimental studies on vertical infection of mice with Japanese encephalitis virus. I. Effect of mouse strain on placental and fetal infection.", "content": "An experiment was carried out with mice to study the effect of the mouse strain on the establishment of experimental vertical infection with Japanese encephalitis virus. Mice of various inbred strains were inoculated with a field strain of virus on the 7th day of pregnancy. An attempt was made on them to recover the virus from the placenta and fetuses. As a result, there were differences in the rate of placental and fetal infection among the mouse strains used. It was clarified that vertical infection could be established experimentally in some selected mouse strains. There was not always a parallel relationship between the rate of placental and fetal infection and the severity of viremia or visceral infection in the dam.", "contents": "Experimental studies on vertical infection of mice with Japanese encephalitis virus. I. Effect of mouse strain on placental and fetal infection. An experiment was carried out with mice to study the effect of the mouse strain on the establishment of experimental vertical infection with Japanese encephalitis virus. Mice of various inbred strains were inoculated with a field strain of virus on the 7th day of pregnancy. An attempt was made on them to recover the virus from the placenta and fetuses. As a result, there were differences in the rate of placental and fetal infection among the mouse strains used. It was clarified that vertical infection could be established experimentally in some selected mouse strains. There was not always a parallel relationship between the rate of placental and fetal infection and the severity of viremia or visceral infection in the dam."}
{"id": "PMID:185533", "title": "Cell surface antigens detected in cell lines established from lymphomatous Papio hamadryas and Macaca arctoides monkeys.", "content": "Cell surface antigens associated with bone marrow cell cultures from leukemic monkeys of species Papio hamadryas and Macacus arctoides were visualized by means of an indirect immunofluorescence method with sera from leukemic baboons. The same immune serum gave two types of immunofluorescence, depending on the origin of the target cells. Fluorescence of the ring-reaction type was seen with Papio hamadryas bone marrow cell cultures growing in suspension and containing the baboon herpesvirus, whereas the patchy type of fluorescence was noted with monolayer bone marrow cell cultures from Macaca arctoides origin, containing type-C oncornavirus but not the herpesvirus particles. Absorption experiments showed that antibodies responsible for the patchy type of immunofluorescence could be absorbed with a disintegrated type-C baboon oncornavirus, and not with baboon lymphoblastoid cell lines containing the herpesvirus nor with human lymphoblastoid cell lines containing the Epstein-Barr virus.", "contents": "Cell surface antigens detected in cell lines established from lymphomatous Papio hamadryas and Macaca arctoides monkeys. Cell surface antigens associated with bone marrow cell cultures from leukemic monkeys of species Papio hamadryas and Macacus arctoides were visualized by means of an indirect immunofluorescence method with sera from leukemic baboons. The same immune serum gave two types of immunofluorescence, depending on the origin of the target cells. Fluorescence of the ring-reaction type was seen with Papio hamadryas bone marrow cell cultures growing in suspension and containing the baboon herpesvirus, whereas the patchy type of fluorescence was noted with monolayer bone marrow cell cultures from Macaca arctoides origin, containing type-C oncornavirus but not the herpesvirus particles. Absorption experiments showed that antibodies responsible for the patchy type of immunofluorescence could be absorbed with a disintegrated type-C baboon oncornavirus, and not with baboon lymphoblastoid cell lines containing the herpesvirus nor with human lymphoblastoid cell lines containing the Epstein-Barr virus."}
{"id": "PMID:185534", "title": "Culture of human cells obtained with DNA from chick Rous sarcoma.", "content": "An infectious process was reproduced in the culture of chick embryo cells by means of DNA isolated from Rous chick sarcoma tissue (Carr-Zilber strain). This DNA preparation displays biological activity also in the culture of human embryo diploid cells (HEDC) which is manifested in: 1. discontinuous synthesis of avian oncovirus group-specific antigen; 2. enhancement of proliferative activity and morphological transformation of human cells; 3. continuous presence of virus-specific sequences as revealed by DNA/RNA hybridization. Producing complete oncornavirus by means of DNA isolated from Rous chick sarcoma in HEDC was unsuccessful. DNA preparation from gs negative chick embryo cells shows no infectious activity in HEDC culture.", "contents": "Culture of human cells obtained with DNA from chick Rous sarcoma. An infectious process was reproduced in the culture of chick embryo cells by means of DNA isolated from Rous chick sarcoma tissue (Carr-Zilber strain). This DNA preparation displays biological activity also in the culture of human embryo diploid cells (HEDC) which is manifested in: 1. discontinuous synthesis of avian oncovirus group-specific antigen; 2. enhancement of proliferative activity and morphological transformation of human cells; 3. continuous presence of virus-specific sequences as revealed by DNA/RNA hybridization. Producing complete oncornavirus by means of DNA isolated from Rous chick sarcoma in HEDC was unsuccessful. DNA preparation from gs negative chick embryo cells shows no infectious activity in HEDC culture."}
{"id": "PMID:185535", "title": "Humoral antibodies to the capsid antigen of Epstein-Barr virus in Hodgkin's disease.", "content": "By the method of indirect immunofluorescence it has been shown in P3HR-I cells that sera from patients with Hodgkin's disease contain high titers of humoral antibodies to the capsid antigen of Epstein-Barr virus (EBV). Higher titers of antibodies of EBV were found in histological variants of Hodgkin's disease with an unfavorable course. The variant of lymphocyte depletion is accomplished by higher titers of the virus and poorer prognosis than the nodular-sclerotic variant having a course with lower titers of antibodies and better prognosis. At the same time, the level of antibodies does not depend on the results of the therapy applied. In the sera of patients with reticulosarcoma or lymphosarcoma no increase in the level of antibodies to EBV has been discovered in comparison with a group of healthy donors; in acute leukemia a certain tendency to decrease in the level of antibodies to this virus can be observed.", "contents": "Humoral antibodies to the capsid antigen of Epstein-Barr virus in Hodgkin's disease. By the method of indirect immunofluorescence it has been shown in P3HR-I cells that sera from patients with Hodgkin's disease contain high titers of humoral antibodies to the capsid antigen of Epstein-Barr virus (EBV). Higher titers of antibodies of EBV were found in histological variants of Hodgkin's disease with an unfavorable course. The variant of lymphocyte depletion is accomplished by higher titers of the virus and poorer prognosis than the nodular-sclerotic variant having a course with lower titers of antibodies and better prognosis. At the same time, the level of antibodies does not depend on the results of the therapy applied. In the sera of patients with reticulosarcoma or lymphosarcoma no increase in the level of antibodies to EBV has been discovered in comparison with a group of healthy donors; in acute leukemia a certain tendency to decrease in the level of antibodies to this virus can be observed."}
{"id": "PMID:185536", "title": "A study on the relation between the Epstein-Barr virus and some forms of malignant tumors in children.", "content": "The presence of antibodies to the virus capsid antigen of the Epstein-Barr virus was established in the sera of children from different forms of neoplasms with the aid of the indirect method of immunofluorescence according to Henle. 69 sera were studied from children with Wilm's tumor, teratoblastoma, reticulosarcoma, neuroblastoma, sarcoma and also from children with benignant tumors. As control served sera from healthy children of corresponding age. As test cells synthesizing the virus capsid antigen the authors utilized a suspension culture of P3HR-I cells, being one of the clones of Burkitt's lymphoma. The performed investigations have shown that in no one group of children with tumor could there be discovered an increase in the content of antibodies to the Epstein-Barr virus in comparison to controls. It has also been revealed that the spread of the Epstein-Barr virus in different groups of patients and healthy children fluctuated between 83 and 100%.", "contents": "A study on the relation between the Epstein-Barr virus and some forms of malignant tumors in children. The presence of antibodies to the virus capsid antigen of the Epstein-Barr virus was established in the sera of children from different forms of neoplasms with the aid of the indirect method of immunofluorescence according to Henle. 69 sera were studied from children with Wilm's tumor, teratoblastoma, reticulosarcoma, neuroblastoma, sarcoma and also from children with benignant tumors. As control served sera from healthy children of corresponding age. As test cells synthesizing the virus capsid antigen the authors utilized a suspension culture of P3HR-I cells, being one of the clones of Burkitt's lymphoma. The performed investigations have shown that in no one group of children with tumor could there be discovered an increase in the content of antibodies to the Epstein-Barr virus in comparison to controls. It has also been revealed that the spread of the Epstein-Barr virus in different groups of patients and healthy children fluctuated between 83 and 100%."}
{"id": "PMID:185538", "title": "[Oily contrast medium in liquor space following myelography. A clinical-radiological study on extent, velocity and ways of elimination of monoiodine stearate].", "content": "In 32 patients neurological and radiological studies were done after spinal myelography using 5 ml of monoidostearate. The route and speed of elimination of the contrast medium remaining intrathecally have been observed over 2 years, establishing correlations with the way and conditions of administration. In the case of active lumbar drainage from the puncture channel after lumbar instillation of contrast medium or after lumbar puncture, a quick and sometimes massive extrathecal and extravertebral leakage, reaching 1/3 of the applied contrast medium, has been observed in 80%-90% of the cases during the first days and weeks. During the first year, the mean contrast medium elimination was 50%. In the case of a single cisternal instillation of contrast medium, no leakage was found, the elimination was 0-8-1-0 ml/year. The importance of \"lumbar puncture drainage\" becomes evident, as well as its activity which lasts up to 19 days. The possible routes of leakage (migration) of the contrast medium are discussed.", "contents": "[Oily contrast medium in liquor space following myelography. A clinical-radiological study on extent, velocity and ways of elimination of monoiodine stearate]. In 32 patients neurological and radiological studies were done after spinal myelography using 5 ml of monoidostearate. The route and speed of elimination of the contrast medium remaining intrathecally have been observed over 2 years, establishing correlations with the way and conditions of administration. In the case of active lumbar drainage from the puncture channel after lumbar instillation of contrast medium or after lumbar puncture, a quick and sometimes massive extrathecal and extravertebral leakage, reaching 1/3 of the applied contrast medium, has been observed in 80%-90% of the cases during the first days and weeks. During the first year, the mean contrast medium elimination was 50%. In the case of a single cisternal instillation of contrast medium, no leakage was found, the elimination was 0-8-1-0 ml/year. The importance of \"lumbar puncture drainage\" becomes evident, as well as its activity which lasts up to 19 days. The possible routes of leakage (migration) of the contrast medium are discussed."}
{"id": "PMID:185543", "title": "Proposal of a new model with dopaminergic-cholinergic interactions for neuropharmacological investigations.", "content": "The motor system of Dugesia gonocephala shows a striking similarity with the extrapyramidal system of high vertebrates and of man with the evidence of correlations between dopaminergic and cholinergic neurons. The utilization of this model seems to be useful in testing drugs which presumably act on dopaminergic or cholinergic transmission. In this model, the quantification of animal behaviour seems considerably easier when compared with the difficulties met in other animal models commonly employed. Besides, it might be anticipated that this model, if correctly used, can display interesting perspectives also in neuroendocrinological investigations.", "contents": "Proposal of a new model with dopaminergic-cholinergic interactions for neuropharmacological investigations. The motor system of Dugesia gonocephala shows a striking similarity with the extrapyramidal system of high vertebrates and of man with the evidence of correlations between dopaminergic and cholinergic neurons. The utilization of this model seems to be useful in testing drugs which presumably act on dopaminergic or cholinergic transmission. In this model, the quantification of animal behaviour seems considerably easier when compared with the difficulties met in other animal models commonly employed. Besides, it might be anticipated that this model, if correctly used, can display interesting perspectives also in neuroendocrinological investigations."}
{"id": "PMID:185544", "title": "Two cases of glomus tumour treated by unusual embolization.", "content": "Two cases of glomus tumour treated by the catheterization technique are reported. In the first case, after it was found impossible to catheterize the external carotid artery by the femoral route, the external carotid was punctured directly, became spasmodic and the catheter could not be introduced, so the inner wall of the external carotid was eroded by manipulating the tip of the metallic guide. This resulted in complete occlusion of the artery 1 cm above the bifurcation of the common carotid. The second case was first treated by embolization of the ascending pharyngeal artery, but with only transitory improvement, so, after 2 months, additional embolization was performed via the vertebral artery, which was followed by immediate and lasting improvement.", "contents": "Two cases of glomus tumour treated by unusual embolization. Two cases of glomus tumour treated by the catheterization technique are reported. In the first case, after it was found impossible to catheterize the external carotid artery by the femoral route, the external carotid was punctured directly, became spasmodic and the catheter could not be introduced, so the inner wall of the external carotid was eroded by manipulating the tip of the metallic guide. This resulted in complete occlusion of the artery 1 cm above the bifurcation of the common carotid. The second case was first treated by embolization of the ascending pharyngeal artery, but with only transitory improvement, so, after 2 months, additional embolization was performed via the vertebral artery, which was followed by immediate and lasting improvement."}
{"id": "PMID:185547", "title": "Glioblastoma multiforme and the meningeal syndrome.", "content": "Brain tumors rarely may produce acute steile meningitis (the meningeal syndrome) resulting from the spillage of blood, lipid products of tumor necrosis, or malignant cells into the cerebrospinal fluid (CSF). The frequency of the associated meningeal syndrome is a function of tumor type and of the tproximity of tumor necrosis to the ventricles. The meningeal syndromes of lipid-induced chemical inflammation are seen most commonly with epidermoids, craniopharyngiomas, and infarcted pituitary adenomas. I report a patient with the rare association of the meningeal syndrome with glioblastoma multiforme. The lipid irritants of glioblastomas and craniopharyngiomas are similar chemically and can be detected in the CSF. The anti-inflammatory and immunosuppressant properties of steroids provide a rational basis for their efficacy in treatment of the syndrome.", "contents": "Glioblastoma multiforme and the meningeal syndrome. Brain tumors rarely may produce acute steile meningitis (the meningeal syndrome) resulting from the spillage of blood, lipid products of tumor necrosis, or malignant cells into the cerebrospinal fluid (CSF). The frequency of the associated meningeal syndrome is a function of tumor type and of the tproximity of tumor necrosis to the ventricles. The meningeal syndromes of lipid-induced chemical inflammation are seen most commonly with epidermoids, craniopharyngiomas, and infarcted pituitary adenomas. I report a patient with the rare association of the meningeal syndrome with glioblastoma multiforme. The lipid irritants of glioblastomas and craniopharyngiomas are similar chemically and can be detected in the CSF. The anti-inflammatory and immunosuppressant properties of steroids provide a rational basis for their efficacy in treatment of the syndrome."}
{"id": "PMID:185552", "title": "Herpesvirus hominis type II infections in asymptomatic pregnant women.", "content": "This study was designed to determine the incidence of previous and current herpesvirus hominis Type II infections in asymptomatic pregnant women. Sera were obtained from 985 patients for detection of Type I and II herpesvirus hominis antibodies. In addition 770 cervical and 211 amniotic fluid cultures for herpesvirus hominis Type II were performed. Identification of previous herpesvirus hominis infection was determined in 352 patients (35.7%) by calculation of a Type II/I antibody index of 85 or greater. Type II herpesvirus hominis was isolated from five cervical cultures for a 0.65% antepartum incidence of infection. None of the amniotic fluid cultures demonstrated virus. The significance of these findings is discussed.", "contents": "Herpesvirus hominis type II infections in asymptomatic pregnant women. This study was designed to determine the incidence of previous and current herpesvirus hominis Type II infections in asymptomatic pregnant women. Sera were obtained from 985 patients for detection of Type I and II herpesvirus hominis antibodies. In addition 770 cervical and 211 amniotic fluid cultures for herpesvirus hominis Type II were performed. Identification of previous herpesvirus hominis infection was determined in 352 patients (35.7%) by calculation of a Type II/I antibody index of 85 or greater. Type II herpesvirus hominis was isolated from five cervical cultures for a 0.65% antepartum incidence of infection. None of the amniotic fluid cultures demonstrated virus. The significance of these findings is discussed."}
{"id": "PMID:185553", "title": "Malignant mixed germ cell tumors of the ovary. A clinical and pathologic analysis of 30 cases.", "content": "The clinical and pathologic features of 30 ovarian mixed germ cell tumors (neoplasms containing combinations of malignant germ cell elements) were studied to determine their behavior and to compare them with pure forms of malignant germ cell tumors. Dysgerminoma was the most common constituent, found in 24 (80%), followed by endodermal sinus tumor in 21 (70%), teratoma in 16 (53%), choriocarcinoma in 6 (20%), and embryonal carcinoma in 5 (16%). The actuarial survival for the entire group was 46%, and for patients with Stage I tumors it was 50%. The most important factors in predicting the prognosis for patients with Stage I disease was the size and the histologic composition of the neoplasm. If more than one-third of a Stage I neoplasm was composed of endodermal sinus tumor, choriocarcinoma, or Grade 3 teratoma, the prognosis was poor, whereas if the tumor contained less than one-third of these components or contained combinations of dysgerminoma, embryonal carcinoma, or Grade 1 or 2 teratoma, the prognosis was excellent. All patients whose neoplasm was less than 10 cm in maximum diameter survived, regardless of the composition of the tumor. Positive pregnancy tests in nonpregnant patients reflected the presence of either frank choriocarcinoma or scattered syncytiotrophoblastic giant cells. The latter did not appear to alter the prognosis. The finding of elevated serum levels of human chorionic gonadotropin (hCG) in 38% of the nonpregnant patients suggested that serial serum assays for hCG might be useful in staging and monitoring the response to treatment in these patients.", "contents": "Malignant mixed germ cell tumors of the ovary. A clinical and pathologic analysis of 30 cases. The clinical and pathologic features of 30 ovarian mixed germ cell tumors (neoplasms containing combinations of malignant germ cell elements) were studied to determine their behavior and to compare them with pure forms of malignant germ cell tumors. Dysgerminoma was the most common constituent, found in 24 (80%), followed by endodermal sinus tumor in 21 (70%), teratoma in 16 (53%), choriocarcinoma in 6 (20%), and embryonal carcinoma in 5 (16%). The actuarial survival for the entire group was 46%, and for patients with Stage I tumors it was 50%. The most important factors in predicting the prognosis for patients with Stage I disease was the size and the histologic composition of the neoplasm. If more than one-third of a Stage I neoplasm was composed of endodermal sinus tumor, choriocarcinoma, or Grade 3 teratoma, the prognosis was poor, whereas if the tumor contained less than one-third of these components or contained combinations of dysgerminoma, embryonal carcinoma, or Grade 1 or 2 teratoma, the prognosis was excellent. All patients whose neoplasm was less than 10 cm in maximum diameter survived, regardless of the composition of the tumor. Positive pregnancy tests in nonpregnant patients reflected the presence of either frank choriocarcinoma or scattered syncytiotrophoblastic giant cells. The latter did not appear to alter the prognosis. The finding of elevated serum levels of human chorionic gonadotropin (hCG) in 38% of the nonpregnant patients suggested that serial serum assays for hCG might be useful in staging and monitoring the response to treatment in these patients."}
{"id": "PMID:185563", "title": "Prostaglandin regulation of adenylate kinases purifed from liver, skeletal muscle, and hepatoma.", "content": "Adenylate kinases, purified from adult rat liver and skeletal muscle and from a fast growing hepatoma, were examined in the presence of a series of prostaglandins. Prostaglandins A1, A2, E1, E2 and F2alpha stimulated liver adenylate kinase 27% to 149%. All of these protaglandins stimulated the skeletal muscle enzyme from 47% to 82%. While prostaglandins A2 and E2 stimulated, prostaglandins A1 and F2alpha inhibited, and prostaglandin E1 was without effect on the hepatoma adenylate kinase.", "contents": "Prostaglandin regulation of adenylate kinases purifed from liver, skeletal muscle, and hepatoma. Adenylate kinases, purified from adult rat liver and skeletal muscle and from a fast growing hepatoma, were examined in the presence of a series of prostaglandins. Prostaglandins A1, A2, E1, E2 and F2alpha stimulated liver adenylate kinase 27% to 149%. All of these protaglandins stimulated the skeletal muscle enzyme from 47% to 82%. While prostaglandins A2 and E2 stimulated, prostaglandins A1 and F2alpha inhibited, and prostaglandin E1 was without effect on the hepatoma adenylate kinase."}
{"id": "PMID:185564", "title": "Cell coat in tumor cells -- effects of trypsin and EDTA: a biochemical and morphological study.", "content": "The effects of trypsin and EDTA on the cell coat of ascites tumor cells were studied by means of biochemical and electron microscopy techniques. EDTA seems to release, by chelation of the Ca2+-bridges, an outer layer of glycoproteins of presumably exogenous origin. On the contrary, trypsin produces a deeper enzymic cleavage which appears to affect the structural integrity of the bilayered cell membrane. The significance of the cell leakage in tumor cells and the effect of EDTA on the modification of this leakage by change of cell membrane permeability are discussed.", "contents": "Cell coat in tumor cells -- effects of trypsin and EDTA: a biochemical and morphological study. The effects of trypsin and EDTA on the cell coat of ascites tumor cells were studied by means of biochemical and electron microscopy techniques. EDTA seems to release, by chelation of the Ca2+-bridges, an outer layer of glycoproteins of presumably exogenous origin. On the contrary, trypsin produces a deeper enzymic cleavage which appears to affect the structural integrity of the bilayered cell membrane. The significance of the cell leakage in tumor cells and the effect of EDTA on the modification of this leakage by change of cell membrane permeability are discussed."}
{"id": "PMID:185565", "title": "Problems in polydactyly of the foot.", "content": "1. Polydactyly should be treated early. 2. Adequate bone and soft tissue should be removed. 3. One arm of the Y should be removed surgically in the incompletely duplicated Y metatarsal. 4. The incompletely duplicated Y metatarsal shaved to form a single shaft may at first be bowed, but will remodel to form normal or nearly normal bone. 5. The wide metatarsal head associated with a duplicated phalanx should be narrowed surgically to avoid the development of a painful bunion. 6. Short block-like metatarsals remain abnormal. 7. Polydactyly associated with a short first metatarsal and congenital hallux varus carriers a poorer treatment prognosis and may require continuing treatment. 8. Postoperative casting and taping should be utilized to prevent angular deformities and encourage normal forefoot contour.", "contents": "Problems in polydactyly of the foot. 1. Polydactyly should be treated early. 2. Adequate bone and soft tissue should be removed. 3. One arm of the Y should be removed surgically in the incompletely duplicated Y metatarsal. 4. The incompletely duplicated Y metatarsal shaved to form a single shaft may at first be bowed, but will remodel to form normal or nearly normal bone. 5. The wide metatarsal head associated with a duplicated phalanx should be narrowed surgically to avoid the development of a painful bunion. 6. Short block-like metatarsals remain abnormal. 7. Polydactyly associated with a short first metatarsal and congenital hallux varus carriers a poorer treatment prognosis and may require continuing treatment. 8. Postoperative casting and taping should be utilized to prevent angular deformities and encourage normal forefoot contour."}
{"id": "PMID:185568", "title": "[Encephalitis and humoral immunity].", "content": "Fourteen children with viral infection of the central nervous system have been examined with respect to their function of humoral immunity. Serum concentrations of immune globulins have been measured and antibody titers determined. Iso- and hetero agglutinins as well as antibodies against diphtheria, pertussis, and tetanus if the children were vaccinated have been measured. Anti viral antibodies were tested if children reported the respective infection in their history. Selective antibody deficiency have been found in three children all of whom had normal serum IgG and two elevated IgM levels. These three children showed complications in the course of infection. Nine children had elevated serum IgM and titers of IgM-antibodies were also in or above the high normal range.", "contents": "[Encephalitis and humoral immunity]. Fourteen children with viral infection of the central nervous system have been examined with respect to their function of humoral immunity. Serum concentrations of immune globulins have been measured and antibody titers determined. Iso- and hetero agglutinins as well as antibodies against diphtheria, pertussis, and tetanus if the children were vaccinated have been measured. Anti viral antibodies were tested if children reported the respective infection in their history. Selective antibody deficiency have been found in three children all of whom had normal serum IgG and two elevated IgM levels. These three children showed complications in the course of infection. Nine children had elevated serum IgM and titers of IgM-antibodies were also in or above the high normal range."}
{"id": "PMID:185569", "title": "[Herpes simplex (author's transl)].", "content": "About 1-2% recurrent herpes simplex infections are seen in adults. In childhood, secondary herpetic infections are very rare. In contrast, primary infections by herpes simplex virus are of great importance: herpes disseminatus neonatorum (type 2), gingivostomatitis herpetica (type 1), eczema herpeticum (type 1; in some cases, also type 2) and keratoconjunctivitis herpetica (type 1). The clinical and therapeutic data are discussed.", "contents": "[Herpes simplex (author's transl)]. About 1-2% recurrent herpes simplex infections are seen in adults. In childhood, secondary herpetic infections are very rare. In contrast, primary infections by herpes simplex virus are of great importance: herpes disseminatus neonatorum (type 2), gingivostomatitis herpetica (type 1), eczema herpeticum (type 1; in some cases, also type 2) and keratoconjunctivitis herpetica (type 1). The clinical and therapeutic data are discussed."}
{"id": "PMID:185575", "title": "[Indirect hemagglutination test for detection of antibodies to cytomegalovirus in blood collected on blotting paper (author's transl)].", "content": "Indirect hemagglutination test for detection of antibodies to cytomegalovirus is highly sensitive and reproducible, if employed in well-defined conditions. Standardization of the various factors involved is necessary as well as their reciprocal equilibrium : sheep erythrocytes, antigen, dilution of tanin, buffers quality. The hemagglutination test can be performed on small volumes such as blood collection on blotting paper (PKU). Antibody titers were compared in the serum and the blood so collected in 104 subjects : the results were very similar and no \"false negative\" were found in any case. This way of collecting blood and hemagglutination are technical improvements in epidemiologic studies of cytomegalovirus infection. It can be hoped they will be adapted to other group herpes infections.", "contents": "[Indirect hemagglutination test for detection of antibodies to cytomegalovirus in blood collected on blotting paper (author's transl)]. Indirect hemagglutination test for detection of antibodies to cytomegalovirus is highly sensitive and reproducible, if employed in well-defined conditions. Standardization of the various factors involved is necessary as well as their reciprocal equilibrium : sheep erythrocytes, antigen, dilution of tanin, buffers quality. The hemagglutination test can be performed on small volumes such as blood collection on blotting paper (PKU). Antibody titers were compared in the serum and the blood so collected in 104 subjects : the results were very similar and no \"false negative\" were found in any case. This way of collecting blood and hemagglutination are technical improvements in epidemiologic studies of cytomegalovirus infection. It can be hoped they will be adapted to other group herpes infections."}
{"id": "PMID:185576", "title": "Polygraphic studies of normal infants during the first six months of life. I. Heart rate and variability as a function of state.", "content": "This study examined spontaneous heart rate (HR) and variability as a function of age and sleep state in eight normal full term infants from birth to 6 months of age. Heart rates recorded during sleep were lower and less regular at 1 week (quiet sleep (QS) mean rate= 128, interquartile range = 6.4 beats/min; rapid eye movement (REM) = 134.5, 11.6) than at 1 month (QS = 138.6, 3.4; REM 139.6, 4.2). Rate  decreased sharply from 1 to 3 months (QS = 118; REM 123.8) and decreased only slightly therafter (6-month QS = 113.5; REM 118.9). Variability decreased rapidly in REM from 2 to 4 months (from 11.4 to 9.1) and less quickly from 4 to 6 months (from 9.1 to 8.2), while QS variability decreased at 1 month (from 6.4 to 5.7) and became stable from that point (6.0 at 6 months). Waking heart rate and variability were both relatively low at 1 week (163, 11.2 beats/min) and increased from that age to 1 month (167.4, 14.3). Rate decreased rapidly in waking at 3 months (152 beats/min) and more slowly therafter (152 beats/min at 4 months, 149 beats/min at 6 months), whereas variability remained elevated until after 3 months, becoming stable at a lower level during later infancy (3 months = 14.8,6 months 11.7). Lowest values of rate and variability were found in QS and the highest values were found in waking at all ages, except at 1 week. Heart rates during REM closely approximated those in QS, whereas variability values more closely resembled those of waking.", "contents": "Polygraphic studies of normal infants during the first six months of life. I. Heart rate and variability as a function of state. This study examined spontaneous heart rate (HR) and variability as a function of age and sleep state in eight normal full term infants from birth to 6 months of age. Heart rates recorded during sleep were lower and less regular at 1 week (quiet sleep (QS) mean rate= 128, interquartile range = 6.4 beats/min; rapid eye movement (REM) = 134.5, 11.6) than at 1 month (QS = 138.6, 3.4; REM 139.6, 4.2). Rate  decreased sharply from 1 to 3 months (QS = 118; REM 123.8) and decreased only slightly therafter (6-month QS = 113.5; REM 118.9). Variability decreased rapidly in REM from 2 to 4 months (from 11.4 to 9.1) and less quickly from 4 to 6 months (from 9.1 to 8.2), while QS variability decreased at 1 month (from 6.4 to 5.7) and became stable from that point (6.0 at 6 months). Waking heart rate and variability were both relatively low at 1 week (163, 11.2 beats/min) and increased from that age to 1 month (167.4, 14.3). Rate decreased rapidly in waking at 3 months (152 beats/min) and more slowly therafter (152 beats/min at 4 months, 149 beats/min at 6 months), whereas variability remained elevated until after 3 months, becoming stable at a lower level during later infancy (3 months = 14.8,6 months 11.7). Lowest values of rate and variability were found in QS and the highest values were found in waking at all ages, except at 1 week. Heart rates during REM closely approximated those in QS, whereas variability values more closely resembled those of waking."}
{"id": "PMID:185578", "title": "Antibody to Varicella-Zoster virus in parturient women and their offspring during the first year of life.", "content": "A nursery outbreak of varicella is reported. Serum from 200 parturient women and 131 of their offspring were studied for antibody to varicella-zoster (V-Z) virus to analyze their immunity to varicella. Antibody titers were measured by the sensitive fluorescent antibody to membrane antigen (FAMA) technique. It was found that approximately 5% to 16% of women of child-bearing age in New York City are susceptible to varicella. Women from Puerto Rico or other subtropical and tropical areas are more likely to be susceptible (16%) than others (5%). Infants born to mothers with detectable V-Z FAMA titers almost always had detectable V-Z antibody at birth. In serial serum specimens obtained from 67 initially seropositive babies during the first year of life, it was found that by 6 months of age most infants were no longer passively protected against varicella. These observations may explain why varicella is not uncommonly observed in young babies.", "contents": "Antibody to Varicella-Zoster virus in parturient women and their offspring during the first year of life. A nursery outbreak of varicella is reported. Serum from 200 parturient women and 131 of their offspring were studied for antibody to varicella-zoster (V-Z) virus to analyze their immunity to varicella. Antibody titers were measured by the sensitive fluorescent antibody to membrane antigen (FAMA) technique. It was found that approximately 5% to 16% of women of child-bearing age in New York City are susceptible to varicella. Women from Puerto Rico or other subtropical and tropical areas are more likely to be susceptible (16%) than others (5%). Infants born to mothers with detectable V-Z FAMA titers almost always had detectable V-Z antibody at birth. In serial serum specimens obtained from 67 initially seropositive babies during the first year of life, it was found that by 6 months of age most infants were no longer passively protected against varicella. These observations may explain why varicella is not uncommonly observed in young babies."}
{"id": "PMID:185580", "title": "Metabolic control of respiratory neuronal activity and the accompanying changes in breathing movements of the rabbit. 1. Mainpulation of inspiratory and expiratory-inspiratory neurons.", "content": "The property of the neuronal membrane to be permeable to metabolic modifiers of two regulatory enzymes has been utilized to manipulate the spike activity of inspiratory (I) and expiratory-inspiratory (EI) neurons of the bulbar respiratory centre. The neurons have been classified according to their response to lung distention or collapse (alpha- or beta-type) and to hyperventilation (tonic firing denoted by \"+\", cessation of activity by \"-\"). Using extracellular microelectrodes for single unit recording, the medulla oblongata was superfused with a metabolite-containing CSF. The various neuronal sub-types exhibited a differential activating or inhibitory response to one or several metabolic effectors. For example Ialpha+ units were activated by 5 mM glucose-6-phosphatase (G-6-P) and 3.5 mM 3-phosphoglycerate (3-PGA), which both inhibited Ibeta+ neurons, while 5 mM AMP inhibited Ialpha+ much more strongly than Ibeta+ cells. The spike density of Ialpha- and Ibeta- neurons was increased in the presence of 2.5 mM fructose-6-phosphate and 3.5--5 mM AMP, but became reduced by G-6-P. In contrast, 3 mM fructose-1,6-diphosphate and 5 mM 3-PGA activated the Ialpha- but inhibited the Ibeta- neurons. The EIbeta units were characteristically activated by 10 mM citrate, which inhibited all I-type neurons. Activations of the Ialpha and Ibeta neurons led to an accelerated respiratory rate and a higher tidal volume, while the opposite was true for EIbeta neurons. Intravenous injection of metabolites could not duplicate the striking effects under local applications.", "contents": "Metabolic control of respiratory neuronal activity and the accompanying changes in breathing movements of the rabbit. 1. Mainpulation of inspiratory and expiratory-inspiratory neurons. The property of the neuronal membrane to be permeable to metabolic modifiers of two regulatory enzymes has been utilized to manipulate the spike activity of inspiratory (I) and expiratory-inspiratory (EI) neurons of the bulbar respiratory centre. The neurons have been classified according to their response to lung distention or collapse (alpha- or beta-type) and to hyperventilation (tonic firing denoted by \"+\", cessation of activity by \"-\"). Using extracellular microelectrodes for single unit recording, the medulla oblongata was superfused with a metabolite-containing CSF. The various neuronal sub-types exhibited a differential activating or inhibitory response to one or several metabolic effectors. For example Ialpha+ units were activated by 5 mM glucose-6-phosphatase (G-6-P) and 3.5 mM 3-phosphoglycerate (3-PGA), which both inhibited Ibeta+ neurons, while 5 mM AMP inhibited Ialpha+ much more strongly than Ibeta+ cells. The spike density of Ialpha- and Ibeta- neurons was increased in the presence of 2.5 mM fructose-6-phosphate and 3.5--5 mM AMP, but became reduced by G-6-P. In contrast, 3 mM fructose-1,6-diphosphate and 5 mM 3-PGA activated the Ialpha- but inhibited the Ibeta- neurons. The EIbeta units were characteristically activated by 10 mM citrate, which inhibited all I-type neurons. Activations of the Ialpha and Ibeta neurons led to an accelerated respiratory rate and a higher tidal volume, while the opposite was true for EIbeta neurons. Intravenous injection of metabolites could not duplicate the striking effects under local applications."}
{"id": "PMID:185581", "title": "Metabolic control of respiratory neuronal activity and the accompanying changey-expiratory neurons.", "content": "Expiratory-related neurons have been classified according to their phase relation within the respiratory cycle, their response to lung distension and collapse (alpha- and beta-type), and to hyperventilation (tonic firing denoted by \"+\", cessation of activity by \"-\"). The dorsal surface of the medulla oblongata was superfused with a metabolite-containing CSF solution and the activity of expiratory (E) and inspiratory-expiratory (IE) neurons was extracellulary recorded. The neuronal sub-types established by their functional behaviour could equally be distinguished by their differential response to one or several metabolites. In contrast to inspiratory (I) neurons, Ealpha- Ebeta-, Ebeta- and IEbeta- neurons are inhibited by 3.5 mM AMP, but are activated by 10 mM citrate (with the exception of Ebeta+ units). Furthermore I cells are activated by ATP, while Ealpha and Ebeta units become inhibited. Vagotomy in some instances affected the response of some IEbeta units. An increase in spike density of IEbeta+ and Ealpha- cells is paralleled by a reduction of both the respiratory rate and the tidal volume, while a lower spike density in IEbeta+, IEbeta- and Ealpha- units is accompanied by increases in respiratory rate and tidal volume. In the case of Ebeta+ and Ebeta- cells lower activity is associated with an increased tidal volume. No metabolite-induced changes could be obtained with cardiovascular or unspecific reticular neurons.", "contents": "Metabolic control of respiratory neuronal activity and the accompanying changey-expiratory neurons. Expiratory-related neurons have been classified according to their phase relation within the respiratory cycle, their response to lung distension and collapse (alpha- and beta-type), and to hyperventilation (tonic firing denoted by \"+\", cessation of activity by \"-\"). The dorsal surface of the medulla oblongata was superfused with a metabolite-containing CSF solution and the activity of expiratory (E) and inspiratory-expiratory (IE) neurons was extracellulary recorded. The neuronal sub-types established by their functional behaviour could equally be distinguished by their differential response to one or several metabolites. In contrast to inspiratory (I) neurons, Ealpha- Ebeta-, Ebeta- and IEbeta- neurons are inhibited by 3.5 mM AMP, but are activated by 10 mM citrate (with the exception of Ebeta+ units). Furthermore I cells are activated by ATP, while Ealpha and Ebeta units become inhibited. Vagotomy in some instances affected the response of some IEbeta units. An increase in spike density of IEbeta+ and Ealpha- cells is paralleled by a reduction of both the respiratory rate and the tidal volume, while a lower spike density in IEbeta+, IEbeta- and Ealpha- units is accompanied by increases in respiratory rate and tidal volume. In the case of Ebeta+ and Ebeta- cells lower activity is associated with an increased tidal volume. No metabolite-induced changes could be obtained with cardiovascular or unspecific reticular neurons."}
{"id": "PMID:185582", "title": "Metabolic control of respiratory neuronal activity and the accompanying changes in breathing movements of the rabbit. III. Phase shifts in respiratory neurons induced by inflation and collapse of the lung, hyperventilation, or metabolic modifiers.", "content": "Phase shifts between inspiratory-related and expiratory-related discharge patterns can be reversibly induced in respiratory neurons following volume changes of the lung, hypocapnic apnea as a result of hyperventilation, or superfusion with certain metabolic modifiers. Phase-spanning expiratory-inspiratory or inspiratory-expiratory discharges are frequently induced in those neurons which are activated either by pulmonary stretch receptors or collapse afferents. The same is true for regulatory effectors which activate key steps of the neuronal metabolism such as ADP, 3-phosphoglycerate, L-glutamine, fructose-6-phosphate and fructose-1,6-diphosphate. In contrast, inhibitory vagal inputs or superfusion with citrate, an inhibitory metabolic modifier, revert preexisting expiratory-inspiratory discharges into a phase-coupled inspiratory pattern. It is postulated that the respiratory neuronal networks represents a time-optimal control system which strives to adjust to a new equilibrium value in a minimum of time, following a given mechanical or chemical perturbation. Following the hypothesis advanced by Cohen (1974) that the phase-spanning units modulate the activity of the in-phase neurons, it is suggested that the additional recruitment of expiratory-inspiratory and inspiratory-expiratory units provides a measure of the quality of time-optimal control and hence a performance index of the system.", "contents": "Metabolic control of respiratory neuronal activity and the accompanying changes in breathing movements of the rabbit. III. Phase shifts in respiratory neurons induced by inflation and collapse of the lung, hyperventilation, or metabolic modifiers. Phase shifts between inspiratory-related and expiratory-related discharge patterns can be reversibly induced in respiratory neurons following volume changes of the lung, hypocapnic apnea as a result of hyperventilation, or superfusion with certain metabolic modifiers. Phase-spanning expiratory-inspiratory or inspiratory-expiratory discharges are frequently induced in those neurons which are activated either by pulmonary stretch receptors or collapse afferents. The same is true for regulatory effectors which activate key steps of the neuronal metabolism such as ADP, 3-phosphoglycerate, L-glutamine, fructose-6-phosphate and fructose-1,6-diphosphate. In contrast, inhibitory vagal inputs or superfusion with citrate, an inhibitory metabolic modifier, revert preexisting expiratory-inspiratory discharges into a phase-coupled inspiratory pattern. It is postulated that the respiratory neuronal networks represents a time-optimal control system which strives to adjust to a new equilibrium value in a minimum of time, following a given mechanical or chemical perturbation. Following the hypothesis advanced by Cohen (1974) that the phase-spanning units modulate the activity of the in-phase neurons, it is suggested that the additional recruitment of expiratory-inspiratory and inspiratory-expiratory units provides a measure of the quality of time-optimal control and hence a performance index of the system."}
{"id": "PMID:185583", "title": "Junctional and extrajunctional acetylcholine receptors in normal and denervated frog muscle fibres. Noise analysis experiments with different agonists.", "content": "Ionic channel properties of acetylcholine receptors located in, in the vicinity of, or far away from a frog neuromuscular junction were investigated by noise analysis of drug induced current fluctuations. For drugs applied to the junction, in certain cases two Lorentzian curves were necessary to describe the data. It is postulated that the reason for this observation is that a contribution from perijunctional receptors was being observed. The conductance of a single channel in the junction was independent of the nature of the agonist and had an average value of 17.9 pS (temperature range 8-25 degrees C, solution buffered with Tris). After denervation for 21 days the conductance gamma was 7.5 pS at extrajunctional locations. In the close neighbourhood of the junction (peri-junctional receptors) values were found between 4 and 19 pS. The mean value of the open channel life-time tau in the endplate exposed to acetylcholine was 2.4 ms at 8-11 degrees C. This value was 0.90 ms with carbachol, 0.50 ms with succinylcholine, 0.28 ms with decamethonium and 0.45 ms with nicotine. The receptors outside the endplate exhibited tau-values which at a given temperature were 2-3 times larger than those at the endplate. Raising the temperature to 23 degrees C reduced all tau-values by factors of 2-3. It is concluded that at least two types of ACh-receptors with different properties exist in the muscle membrane, possibly produced by ACh-receptive units in different states of aggregation.", "contents": "Junctional and extrajunctional acetylcholine receptors in normal and denervated frog muscle fibres. Noise analysis experiments with different agonists. Ionic channel properties of acetylcholine receptors located in, in the vicinity of, or far away from a frog neuromuscular junction were investigated by noise analysis of drug induced current fluctuations. For drugs applied to the junction, in certain cases two Lorentzian curves were necessary to describe the data. It is postulated that the reason for this observation is that a contribution from perijunctional receptors was being observed. The conductance of a single channel in the junction was independent of the nature of the agonist and had an average value of 17.9 pS (temperature range 8-25 degrees C, solution buffered with Tris). After denervation for 21 days the conductance gamma was 7.5 pS at extrajunctional locations. In the close neighbourhood of the junction (peri-junctional receptors) values were found between 4 and 19 pS. The mean value of the open channel life-time tau in the endplate exposed to acetylcholine was 2.4 ms at 8-11 degrees C. This value was 0.90 ms with carbachol, 0.50 ms with succinylcholine, 0.28 ms with decamethonium and 0.45 ms with nicotine. The receptors outside the endplate exhibited tau-values which at a given temperature were 2-3 times larger than those at the endplate. Raising the temperature to 23 degrees C reduced all tau-values by factors of 2-3. It is concluded that at least two types of ACh-receptors with different properties exist in the muscle membrane, possibly produced by ACh-receptive units in different states of aggregation."}
{"id": "PMID:185584", "title": "A study in vitro of the concentrating defect associated with hypokalaemia and hypercalcaemia.", "content": "The diffusional water permeabilities of collecting ducts in the presence and absence of antidiuretic hormone have been measured in isolated papillae from normal, hypokalaemic and hypercalcaemic rats. In a similar in vitro situation the effect of antidiuretic hormone on the papillary content of cyclic AMP has been measured. The diffusional water permeability of collecting ducts in the absence of antidiuretic hormone did not differ significantly in papillae taken from the different groups of rats. The diffusional water permeability in the presence of ADH was 7.4 +/- 0.2 (S.E.M.) mum s-1 in collecting ducts taken from normal rats. In collecting ducts taken from hypokalaemic or hypercalcaemic rats the corresponding values were 5.9 +/- 0.3 and 5.8 +/- 0.5 mum s-1 respectively. This significant decrease (P less than 0.01) in the response to antidiuretic hormone would shift the point at which distal tubule fluid first attains isotonicity with the interstitium. If this shifts from cortex to medulla a greater amount of water enters the interstitium of the medulla and produces an impairment of maximal urinary concentrating ability and this defect could explain most of the observed results in hypokalaemic and hypercalcaemic. Cyclic AMP content of the tissue after the addition of ADH was reduced in papillae taken from hypokalaemic rats. This reduced activation of adenyl cyclase could be the mechanism responsible for the impaired response in water permeability but it is also possible that there is interference, with the chain of reactions mediating permeability changes, at a separate site.", "contents": "A study in vitro of the concentrating defect associated with hypokalaemia and hypercalcaemia. The diffusional water permeabilities of collecting ducts in the presence and absence of antidiuretic hormone have been measured in isolated papillae from normal, hypokalaemic and hypercalcaemic rats. In a similar in vitro situation the effect of antidiuretic hormone on the papillary content of cyclic AMP has been measured. The diffusional water permeability of collecting ducts in the absence of antidiuretic hormone did not differ significantly in papillae taken from the different groups of rats. The diffusional water permeability in the presence of ADH was 7.4 +/- 0.2 (S.E.M.) mum s-1 in collecting ducts taken from normal rats. In collecting ducts taken from hypokalaemic or hypercalcaemic rats the corresponding values were 5.9 +/- 0.3 and 5.8 +/- 0.5 mum s-1 respectively. This significant decrease (P less than 0.01) in the response to antidiuretic hormone would shift the point at which distal tubule fluid first attains isotonicity with the interstitium. If this shifts from cortex to medulla a greater amount of water enters the interstitium of the medulla and produces an impairment of maximal urinary concentrating ability and this defect could explain most of the observed results in hypokalaemic and hypercalcaemic. Cyclic AMP content of the tissue after the addition of ADH was reduced in papillae taken from hypokalaemic rats. This reduced activation of adenyl cyclase could be the mechanism responsible for the impaired response in water permeability but it is also possible that there is interference, with the chain of reactions mediating permeability changes, at a separate site."}
{"id": "PMID:185585", "title": "The effect of lithium on the permeability response induced in the collecting duct by antidiuretic hormone.", "content": "The diffusional and osmotic water permeability of collecting ducts in isolated papillae of rats' kidneys were measured in papillae taken from normal and lithium pretreated rats. The diffusional water permeability of collecting ducts in papillae from normal rats in the absence of ADH was 4.1 +/- 0.2 (S.E.M.) (n = 18) muM s-1 increasing to 7.2 +/- 0.6 mum s-1 with ADH. Values obtained with lithium (10 mM) in the medium, perfusate or both and in papillae taken from lithium pretreated rats did not differ significantly from the above. The cyclic AMP content of the papillae taken from normal rats was 83 +/- 6 pm mg protein in the absence of ADH and increased to 196 +/- 12 (n = 13) with 500 mu units ml-1 ADH. Lithium 10 mM in the medium did not alter this response. Papillae from lithium pretreated rats had a similar basal level of cyclic AMP but the increment in a lithium (10 mM) medium after ADH was significantly less. These results indicate that the impaired water handling of lithium treated rats is probably not due to a failure of the membrane to increase its permeability to water after ADH. Though lithium does alter the production of cyclic AMP this is not believed to be important regarding any alteration in water permeability. We believe it is probable that lithium interferes with sodium chloride transport at some more proximal nephron segment thereby producing the syndrome of polyuria.", "contents": "The effect of lithium on the permeability response induced in the collecting duct by antidiuretic hormone. The diffusional and osmotic water permeability of collecting ducts in isolated papillae of rats' kidneys were measured in papillae taken from normal and lithium pretreated rats. The diffusional water permeability of collecting ducts in papillae from normal rats in the absence of ADH was 4.1 +/- 0.2 (S.E.M.) (n = 18) muM s-1 increasing to 7.2 +/- 0.6 mum s-1 with ADH. Values obtained with lithium (10 mM) in the medium, perfusate or both and in papillae taken from lithium pretreated rats did not differ significantly from the above. The cyclic AMP content of the papillae taken from normal rats was 83 +/- 6 pm mg protein in the absence of ADH and increased to 196 +/- 12 (n = 13) with 500 mu units ml-1 ADH. Lithium 10 mM in the medium did not alter this response. Papillae from lithium pretreated rats had a similar basal level of cyclic AMP but the increment in a lithium (10 mM) medium after ADH was significantly less. These results indicate that the impaired water handling of lithium treated rats is probably not due to a failure of the membrane to increase its permeability to water after ADH. Though lithium does alter the production of cyclic AMP this is not believed to be important regarding any alteration in water permeability. We believe it is probable that lithium interferes with sodium chloride transport at some more proximal nephron segment thereby producing the syndrome of polyuria."}
{"id": "PMID:185586", "title": "Persistance of intramuscular deposits of vitamin D3 in slaughter pigs.", "content": "In pigs given injections of 1.5 mill IU vitamin D3 in oil intramuscularly 9, 5 or 3 weeks before slaughter residues in the depots were very high (table 1). Certain cuts of pork from pigs treated in this way should therefore be regarded as unacceptably polluted. Furthermore the practise of using oily vitamin D preparations for injection in veterinary medicine appears to be unjustified in modern husbandry.", "contents": "Persistance of intramuscular deposits of vitamin D3 in slaughter pigs. In pigs given injections of 1.5 mill IU vitamin D3 in oil intramuscularly 9, 5 or 3 weeks before slaughter residues in the depots were very high (table 1). Certain cuts of pork from pigs treated in this way should therefore be regarded as unacceptably polluted. Furthermore the practise of using oily vitamin D preparations for injection in veterinary medicine appears to be unjustified in modern husbandry."}
{"id": "PMID:185588", "title": "[Meningo-radiculitis following tick bite].", "content": "The authors report nine cases of acute inflammatory polyradiculoneuritis developing one to eleven weeks after a tick bite, regressive, painful and asymmetrical, with an albumino-cellular reaction in the CSF. They stress the very particular physiognomy of this type of meningo-radiculitis, its seasonal occurrence and the uncertain nature of its pathogenesis.", "contents": "[Meningo-radiculitis following tick bite]. The authors report nine cases of acute inflammatory polyradiculoneuritis developing one to eleven weeks after a tick bite, regressive, painful and asymmetrical, with an albumino-cellular reaction in the CSF. They stress the very particular physiognomy of this type of meningo-radiculitis, its seasonal occurrence and the uncertain nature of its pathogenesis."}
{"id": "PMID:185589", "title": "[Gastrointestinal amyloidosis].", "content": "A series of 29 cases of amyloidosis of the alimentary tract is reported. Five cases (17%) were primary amyloidosis; 14 cases (48%) were amyloidosis secondary to other diseases (such as chronic inflammatory and neoplastic diseases); 10 cases (35%) were amyloidosis of the heredo-familial type connected with Familial Mediterranean Fever. In 23 patients (79%) the diagnosis was established by biopsies, and in 6 more cases on autopsy. Gastrointestinal involvement was found in all age groups. Gastro-enterologic complications observed in the present series include: diarrhea, malabsorption, ileus and gastrointestinal bleeding. In addition other conditions such as jaundice (3 cases), esophagitis and acute hemorrhagic pancreatitis were observed. In 22 patients proteinuria was observed and in 13 patients the nephrotic syndrome. Among 17 patients, in 11 the clinical picture before death was that of terminal renal failure. The survival after diagnosis among 14 patients reached 4 years in 9 cases, and 19 years in one case. The diagnostic value of the rectal biopsy is emphasized.", "contents": "[Gastrointestinal amyloidosis]. A series of 29 cases of amyloidosis of the alimentary tract is reported. Five cases (17%) were primary amyloidosis; 14 cases (48%) were amyloidosis secondary to other diseases (such as chronic inflammatory and neoplastic diseases); 10 cases (35%) were amyloidosis of the heredo-familial type connected with Familial Mediterranean Fever. In 23 patients (79%) the diagnosis was established by biopsies, and in 6 more cases on autopsy. Gastrointestinal involvement was found in all age groups. Gastro-enterologic complications observed in the present series include: diarrhea, malabsorption, ileus and gastrointestinal bleeding. In addition other conditions such as jaundice (3 cases), esophagitis and acute hemorrhagic pancreatitis were observed. In 22 patients proteinuria was observed and in 13 patients the nephrotic syndrome. Among 17 patients, in 11 the clinical picture before death was that of terminal renal failure. The survival after diagnosis among 14 patients reached 4 years in 9 cases, and 19 years in one case. The diagnostic value of the rectal biopsy is emphasized."}
{"id": "PMID:185590", "title": "[Adrenal insufficiencies caused by isolated corticotropic deficiency. 2 cases].", "content": "Isolated adrenocorticotropin deficiencies are rare. Two cases are reported, one, with hypoglycaemia, the other with weakness and hypotension, with a review of the published cases during the past twenty years. The adrenal defect impairs severely the glucocorticoid secretion while aldosteron is normal. Tetracosactid stimulates adrenal secretion. ACTH activity measurable in serum is very low and not affected by metyrapone. Other pituitary secretions are normal. The hypothalamic or pituitary level of the defect will be situated when CRH test available.", "contents": "[Adrenal insufficiencies caused by isolated corticotropic deficiency. 2 cases]. Isolated adrenocorticotropin deficiencies are rare. Two cases are reported, one, with hypoglycaemia, the other with weakness and hypotension, with a review of the published cases during the past twenty years. The adrenal defect impairs severely the glucocorticoid secretion while aldosteron is normal. Tetracosactid stimulates adrenal secretion. ACTH activity measurable in serum is very low and not affected by metyrapone. Other pituitary secretions are normal. The hypothalamic or pituitary level of the defect will be situated when CRH test available."}
{"id": "PMID:185593", "title": "[Low thyrotrope hormone: a new entity].", "content": "The combination of the TRH stimulation of TSH release with the plasma iodide (PII) increase test, which gives a physiological measure of TSH basal activity, allows characterization of a syndrome we have called a low pituitary TSH reserve. These patients were euthyroid, had a normal PII increase test but a mild or no response to TRH. It was chiefly found in acromegaly and diabetes mellitus, after prolonged high levels of thyroid hormones or hypophysectomy. It appears to be a transient state between normal and abnormal thyrotropin function. So the absence of TSH increase after TRH injection can be of diagnostic value only when other tests of thyrotropin function are performed.", "contents": "[Low thyrotrope hormone: a new entity]. The combination of the TRH stimulation of TSH release with the plasma iodide (PII) increase test, which gives a physiological measure of TSH basal activity, allows characterization of a syndrome we have called a low pituitary TSH reserve. These patients were euthyroid, had a normal PII increase test but a mild or no response to TRH. It was chiefly found in acromegaly and diabetes mellitus, after prolonged high levels of thyroid hormones or hypophysectomy. It appears to be a transient state between normal and abnormal thyrotropin function. So the absence of TSH increase after TRH injection can be of diagnostic value only when other tests of thyrotropin function are performed."}
{"id": "PMID:185606", "title": "[Bronchiolo-alveolar cancer].", "content": "The bronchiolo-alveolar adenocarcinoma, less frequent than other types of bronchopulmonary cancers, occurs more frequently during pulmonary fibrosis. Besides a mucous bronchorrhea of little meaning, the clinical manifestations belong to the advanced stages. The X-ray, unreliable and variable, shows a variety of pictures from mono or multinodular ones to pseudopneumonic infiltrates. Usually no information could be derived from bronchoscopy. Positive cytological examination of sputum are unfrequent. Early surgery brings longer remissions than in other types of bronchopulmonary cancer. Diagnosis can only be made from the histology of the exeresis sample. The tumour cells, cuboidal or columnar, are arranged in mono or pluri-stratified layers in the inter-alveolar septa, which progressively become fibrous. This cancer has an original histogenesis: it would originate from the neoplastic metaplasia of type II pneumocytes or of respiratory bronchiole cells, invading the pulmonary alveoli by sliding or by contiguity. Far from the initial foyer, the spreading seems mostly done through airways.", "contents": "[Bronchiolo-alveolar cancer]. The bronchiolo-alveolar adenocarcinoma, less frequent than other types of bronchopulmonary cancers, occurs more frequently during pulmonary fibrosis. Besides a mucous bronchorrhea of little meaning, the clinical manifestations belong to the advanced stages. The X-ray, unreliable and variable, shows a variety of pictures from mono or multinodular ones to pseudopneumonic infiltrates. Usually no information could be derived from bronchoscopy. Positive cytological examination of sputum are unfrequent. Early surgery brings longer remissions than in other types of bronchopulmonary cancer. Diagnosis can only be made from the histology of the exeresis sample. The tumour cells, cuboidal or columnar, are arranged in mono or pluri-stratified layers in the inter-alveolar septa, which progressively become fibrous. This cancer has an original histogenesis: it would originate from the neoplastic metaplasia of type II pneumocytes or of respiratory bronchiole cells, invading the pulmonary alveoli by sliding or by contiguity. Far from the initial foyer, the spreading seems mostly done through airways."}
{"id": "PMID:185603", "title": "Modification of 6-aminopenicillanic acid derivatives.", "content": "In order to prepare intermediate for further transformation of penicillins), and to obtain new derivatives with enlarged spectrum of biological activity some semi-synthetic phenoxyalkanepenicillins were subjected to the esterification, amidation and hydroxyamidation reactions. Hydroxyamidation i.e. synthesis of corresponding penicilline-hydroxamic acids was a complex reaction depending on the structure of hydroxylamine used. The two-directional reaction course, with beta-lactam bond splitting, was specific for unsubstituted hydroxylamine only. A number of new penicilline hydroxamic acids and N-methoxypenicilline amides, with intact and cleaved beta-lactam ring were synthesized.", "contents": "Modification of 6-aminopenicillanic acid derivatives. In order to prepare intermediate for further transformation of penicillins), and to obtain new derivatives with enlarged spectrum of biological activity some semi-synthetic phenoxyalkanepenicillins were subjected to the esterification, amidation and hydroxyamidation reactions. Hydroxyamidation i.e. synthesis of corresponding penicilline-hydroxamic acids was a complex reaction depending on the structure of hydroxylamine used. The two-directional reaction course, with beta-lactam bond splitting, was specific for unsubstituted hydroxylamine only. A number of new penicilline hydroxamic acids and N-methoxypenicilline amides, with intact and cleaved beta-lactam ring were synthesized."}
{"id": "PMID:185608", "title": "Coherent anti-Stokes Raman scattering (CARS) spectra, with resonance enhancement, of cytochrome c and vitamin B12 in dilute aqueous solution.", "content": "Coherent anti-Stokes Raman scattering (CARS) spectra have been obtained for ferrocytochrome c and cyano cobalamin in aqueous solution at millimolar concentrations, using a pair of tunable dye lasers pumped by a pulsed nitrogen laser. Resonance enhancement was obtained by tuning the omega1 laser to the visible absorption bands of the samples. The spectral features correspond to those observed in the conventional resonance Raman spectra. It appears that CARS spectroscopy, with its advantageous fluorescence rejection, can be usefully applied to biological samples by exploiting resonance enhancement. While the background scattering from water is 10 times higher than that of benzene and other aromatic solvents, it is actually at the low end of the scale for most liquids. The anomalously low background of aromatic liquids is thought to result from competition by the unusually efficient stimulated Raman scattering which they display. Off-resonance spectra for both cobalamin and cytochrome c contain negative peaks, i.e., absorption bands in the background. These are interpreted as inverse Raman processes induced by the omega1 photons in the presence of the continuum provided by the background scattering. While both CARS and the inverse Raman effect are subject to resonance enhancement, the wavelength dependence of CARS is evidently steeper.", "contents": "Coherent anti-Stokes Raman scattering (CARS) spectra, with resonance enhancement, of cytochrome c and vitamin B12 in dilute aqueous solution. Coherent anti-Stokes Raman scattering (CARS) spectra have been obtained for ferrocytochrome c and cyano cobalamin in aqueous solution at millimolar concentrations, using a pair of tunable dye lasers pumped by a pulsed nitrogen laser. Resonance enhancement was obtained by tuning the omega1 laser to the visible absorption bands of the samples. The spectral features correspond to those observed in the conventional resonance Raman spectra. It appears that CARS spectroscopy, with its advantageous fluorescence rejection, can be usefully applied to biological samples by exploiting resonance enhancement. While the background scattering from water is 10 times higher than that of benzene and other aromatic solvents, it is actually at the low end of the scale for most liquids. The anomalously low background of aromatic liquids is thought to result from competition by the unusually efficient stimulated Raman scattering which they display. Off-resonance spectra for both cobalamin and cytochrome c contain negative peaks, i.e., absorption bands in the background. These are interpreted as inverse Raman processes induced by the omega1 photons in the presence of the continuum provided by the background scattering. While both CARS and the inverse Raman effect are subject to resonance enhancement, the wavelength dependence of CARS is evidently steeper."}
{"id": "PMID:185609", "title": "Thyroid hormone stimulates de novo growth hormone synthesis in cultured GH1 cells: evidence for the accumulation of a rate limiting RNA species in the induction process.", "content": "We have previously demonstrated with radioimmunoassay techniques that physiologic concentrations of thyroid hormone stimulate an increase in growth hormone production in GH1 cells in culture. In this study, with radiolabel techniques and selective immunoprecipitation, we demonstrate that L-triiodothyronine stimulates growth hormonw production solely by inducing an increase in the de novo synthesis of the polypeptide hormone. L-Triiodothyronine stimulated synthetic rates of growth hormone by 1.5-fold in 1.25 hr, 2-fold in 2.5 hr, to a maximal of 3- to 4-fold after 8.5 hr of incubation. The time interval between significant L-triiodothyronine binding to putative nuclear receptors and a detectable increase in growth hormone synthesis was 45-60 min. Studies on the effect of actinomycin D, 3'-deoxyadenosine, and cycloheximide support the thesis that L-triiodothyronine induces the accumulation of an RNA species which is rate limiting for growth hormone synthesis and lends further support for a primary action of thyroid hormone at the nuclear level.", "contents": "Thyroid hormone stimulates de novo growth hormone synthesis in cultured GH1 cells: evidence for the accumulation of a rate limiting RNA species in the induction process. We have previously demonstrated with radioimmunoassay techniques that physiologic concentrations of thyroid hormone stimulate an increase in growth hormone production in GH1 cells in culture. In this study, with radiolabel techniques and selective immunoprecipitation, we demonstrate that L-triiodothyronine stimulates growth hormonw production solely by inducing an increase in the de novo synthesis of the polypeptide hormone. L-Triiodothyronine stimulated synthetic rates of growth hormone by 1.5-fold in 1.25 hr, 2-fold in 2.5 hr, to a maximal of 3- to 4-fold after 8.5 hr of incubation. The time interval between significant L-triiodothyronine binding to putative nuclear receptors and a detectable increase in growth hormone synthesis was 45-60 min. Studies on the effect of actinomycin D, 3'-deoxyadenosine, and cycloheximide support the thesis that L-triiodothyronine induces the accumulation of an RNA species which is rate limiting for growth hormone synthesis and lends further support for a primary action of thyroid hormone at the nuclear level."}
{"id": "PMID:185610", "title": "Nitrofurans, a group of synthetic antibiotics, with a new mode of action: discrimination of specific messenger RNA classes.", "content": "Nitrofurans, a class of antibacterial drugs in extensive use, interferes with gene expression in a highly specific manner. While in the low dose range (0.5-25 mug/ml), 5-nitro-2-furfurylidene-1-aminohydantoin has no effect on transcription, it inhibits specifically the expression of one class of genes in translation. The specific inhibition concerns the inducible genes. The inhibition of messenger RNA expression occurs at the initiation step. The action of nitrofurans, thus, indicates heterogeneity in the population of mRNA molecules and in the translational machinery and suggests the possibility of selective translational control.", "contents": "Nitrofurans, a group of synthetic antibiotics, with a new mode of action: discrimination of specific messenger RNA classes. Nitrofurans, a class of antibacterial drugs in extensive use, interferes with gene expression in a highly specific manner. While in the low dose range (0.5-25 mug/ml), 5-nitro-2-furfurylidene-1-aminohydantoin has no effect on transcription, it inhibits specifically the expression of one class of genes in translation. The specific inhibition concerns the inducible genes. The inhibition of messenger RNA expression occurs at the initiation step. The action of nitrofurans, thus, indicates heterogeneity in the population of mRNA molecules and in the translational machinery and suggests the possibility of selective translational control."}
{"id": "PMID:185611", "title": "Novel structure at 5'-ends of nascent DNA chains.", "content": "Because of their association with protein short nascent DNA chains in Escherichia coli can be separated from other cellular DNA by chromatography on hydroxylapatite. Protein-free DNA chains of less than 500 nucleotides in length are resistant to degradation from the 5'-end by alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum); EC 3.1.3.1] and spleen phosphodiesterase (oligonucleate 3'-nucleotidohydrolase; EC 3.1.4.18). In contrast, DNA chains containing more than 500 nucleotides are degradable. From these results we conclude that short nascent DNA chains are structurally modified at their 5'-ends. The nature of this structure and its possible functions are discussed.", "contents": "Novel structure at 5'-ends of nascent DNA chains. Because of their association with protein short nascent DNA chains in Escherichia coli can be separated from other cellular DNA by chromatography on hydroxylapatite. Protein-free DNA chains of less than 500 nucleotides in length are resistant to degradation from the 5'-end by alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum); EC 3.1.3.1] and spleen phosphodiesterase (oligonucleate 3'-nucleotidohydrolase; EC 3.1.4.18). In contrast, DNA chains containing more than 500 nucleotides are degradable. From these results we conclude that short nascent DNA chains are structurally modified at their 5'-ends. The nature of this structure and its possible functions are discussed."}
{"id": "PMID:185612", "title": "ATP-PPi exchange activity of progesterone receptor.", "content": "Progesterone receptor preparations from avian oviduct catalyze a pyrophosphate (PPi)-exchange reaction between ATP and 32P-labeled PPi. The reaction requires ATP exclusively and is Mn++-dependent. This enzyme activity is detectable in receptor preparations that have been purified extensively by chromatography on ATP-Sepharose and DEAE-Sephadex columns. Polyacrylamide gel electrophoresis of purified preparations reveals a comigration of [3H]progesterone-receptor complex and the enzyme activity. The PPi-exchange reaction is inhibited by both o-phenanthroline and rifamycin AF/013, which also block the nuclear binding of progesterone receptor. These findings indicate that progesterone receptor may be an enzyme or a subunit of an enzyme that is active in nucleotide metabolism.", "contents": "ATP-PPi exchange activity of progesterone receptor. Progesterone receptor preparations from avian oviduct catalyze a pyrophosphate (PPi)-exchange reaction between ATP and 32P-labeled PPi. The reaction requires ATP exclusively and is Mn++-dependent. This enzyme activity is detectable in receptor preparations that have been purified extensively by chromatography on ATP-Sepharose and DEAE-Sephadex columns. Polyacrylamide gel electrophoresis of purified preparations reveals a comigration of [3H]progesterone-receptor complex and the enzyme activity. The PPi-exchange reaction is inhibited by both o-phenanthroline and rifamycin AF/013, which also block the nuclear binding of progesterone receptor. These findings indicate that progesterone receptor may be an enzyme or a subunit of an enzyme that is active in nucleotide metabolism."}
{"id": "PMID:185613", "title": "Differential synthesis of blocked and unblocked 5'-termini in reovirus mRNA: effect of pyrophosphate and pyrophosphatase.", "content": "Viral mRNA synthesized in vitro by reovirusassociated enzymes contained 5'-terminal ppG, GpppG, or m7GpppGm. Selective synthesis of one type of 5'-end was obtained by adjusting the composition of the transcription reaction mixture based on a series of reactions proposed for formation of blocked, methylated 5'-terminal sequences of mRNA (capformation). The presence of inorganic pyrophosphate increased the proportion of ppG 5'-ends, while addition of pyrophosphatase yielded mRNA with 5'-terminal GpppG, which in the presence of a methyl donor was converted to m7GpppGm.", "contents": "Differential synthesis of blocked and unblocked 5'-termini in reovirus mRNA: effect of pyrophosphate and pyrophosphatase. Viral mRNA synthesized in vitro by reovirusassociated enzymes contained 5'-terminal ppG, GpppG, or m7GpppGm. Selective synthesis of one type of 5'-end was obtained by adjusting the composition of the transcription reaction mixture based on a series of reactions proposed for formation of blocked, methylated 5'-terminal sequences of mRNA (capformation). The presence of inorganic pyrophosphate increased the proportion of ppG 5'-ends, while addition of pyrophosphatase yielded mRNA with 5'-terminal GpppG, which in the presence of a methyl donor was converted to m7GpppGm."}
{"id": "PMID:185614", "title": "In vitro replication of simian virus 40 DNA in a nucleoprotein complex.", "content": "A simian virus 40 (SV40) nucleoprotein complex, extracted from nuclei isolated from a monkey cell line infected with SV40, continued DNA replication in the presence of a nuclear extract, cytosol, ATP, and ATP-regenerating system, and the four deoxyribonucleoside triphosphates. The DNA products of replication were also found as nucleoprotein complexes. Forty percent of the replicating viral DNA, labeled in vivo, was converted into covalently closed, superhelical DNA during incubation in vitro. Although the remaining labeled DNA was not converted into mature viral DNA, it was elongated to its full genome length. Failure to terminate replication successfully was not caused by endonuclease activity, since covalently closed DNA, labeled in vivo, was not damaged during incubation in vitro. When [alpha-32P]dATP was present during the incubation, the label appeared first in replicating DNA and later in mature DNA; no unusual products were labeled in vitro. The covalently closed SV40 DNA made in vitro had the same superhelical density as viral DNA made in vivo. These data demonstrate that viral nucleoprotein complexes (\"minichromosomes\") are able to continue DNA replication outside of the nucleus.", "contents": "In vitro replication of simian virus 40 DNA in a nucleoprotein complex. A simian virus 40 (SV40) nucleoprotein complex, extracted from nuclei isolated from a monkey cell line infected with SV40, continued DNA replication in the presence of a nuclear extract, cytosol, ATP, and ATP-regenerating system, and the four deoxyribonucleoside triphosphates. The DNA products of replication were also found as nucleoprotein complexes. Forty percent of the replicating viral DNA, labeled in vivo, was converted into covalently closed, superhelical DNA during incubation in vitro. Although the remaining labeled DNA was not converted into mature viral DNA, it was elongated to its full genome length. Failure to terminate replication successfully was not caused by endonuclease activity, since covalently closed DNA, labeled in vivo, was not damaged during incubation in vitro. When [alpha-32P]dATP was present during the incubation, the label appeared first in replicating DNA and later in mature DNA; no unusual products were labeled in vitro. The covalently closed SV40 DNA made in vitro had the same superhelical density as viral DNA made in vivo. These data demonstrate that viral nucleoprotein complexes (\"minichromosomes\") are able to continue DNA replication outside of the nucleus."}
{"id": "PMID:185615", "title": "Catabolite modulator factor: a possible mediator of catabolite repression in bacteria.", "content": "Water soluble extracts of Escherichia coli cells have been found to exert an extremely strong repressive effect upon the expression of catabolite sensitive operons. The compound responsible for this activity has been partially purified and proves to be of low molecular weight and heat stable. The effect of this compound, hereafter designated as catabolite modulator factor, is only partially antagonized by adenosine 3':5'-cyclic monophosphate. The possible role of catabolite modulator factor in the physiological regulation of catabolite repression is discussed.", "contents": "Catabolite modulator factor: a possible mediator of catabolite repression in bacteria. Water soluble extracts of Escherichia coli cells have been found to exert an extremely strong repressive effect upon the expression of catabolite sensitive operons. The compound responsible for this activity has been partially purified and proves to be of low molecular weight and heat stable. The effect of this compound, hereafter designated as catabolite modulator factor, is only partially antagonized by adenosine 3':5'-cyclic monophosphate. The possible role of catabolite modulator factor in the physiological regulation of catabolite repression is discussed."}
{"id": "PMID:185616", "title": "V irus and lectin agglutination of erythrocytes: spin label study of membrane lipid-protein interactions.", "content": "Techniques of spin-label electron spin resonance have been used to prove changes in the structure of the lipid phase of erythrocyte membrane after agglutination by viruses and lectins. When chicken erythrocytes are agglutinated by Sendai and influenza viruses and by the lectins concanavalin A and wheat germ agglutinin, the membrane lipid phase becomes more fluid, as detected by three different lipophilic spin-laveled probes. Colchicine, vinblastine, and tetracaine inhibit the fluidization of chicken erythrocyte membrane by Sendai virus, whereas cytochalasin B has no effect. The effect of colchicine was time dependent, the initial inhibition decreasing with longer preincubation times. Extensive treatment of erythrocytes with proteases or neuraminidase, while not altering the bilayer structure, abolishes the effect of Sendai virus on the erythrocyte membrane, suggesting that a change in the interaction of the receptor protein with the lipid phase occurs upon virus attachment. Glutaraldehyde fixation increased the structural rigidity of the chicken erythrocyte membrane and inhibited the effect of viral agglutination. No change in bilayer structure was observed upon agglutination of human erythrocytes or the isolated plasma membranes of either human or chicken erythrocytes. This result is consistent with the drug sensitivity of the effects of agglutination upon chicken erythrocytes, since human erythrocytes and isolated membranes lack microtubule-like structures.", "contents": "V irus and lectin agglutination of erythrocytes: spin label study of membrane lipid-protein interactions. Techniques of spin-label electron spin resonance have been used to prove changes in the structure of the lipid phase of erythrocyte membrane after agglutination by viruses and lectins. When chicken erythrocytes are agglutinated by Sendai and influenza viruses and by the lectins concanavalin A and wheat germ agglutinin, the membrane lipid phase becomes more fluid, as detected by three different lipophilic spin-laveled probes. Colchicine, vinblastine, and tetracaine inhibit the fluidization of chicken erythrocyte membrane by Sendai virus, whereas cytochalasin B has no effect. The effect of colchicine was time dependent, the initial inhibition decreasing with longer preincubation times. Extensive treatment of erythrocytes with proteases or neuraminidase, while not altering the bilayer structure, abolishes the effect of Sendai virus on the erythrocyte membrane, suggesting that a change in the interaction of the receptor protein with the lipid phase occurs upon virus attachment. Glutaraldehyde fixation increased the structural rigidity of the chicken erythrocyte membrane and inhibited the effect of viral agglutination. No change in bilayer structure was observed upon agglutination of human erythrocytes or the isolated plasma membranes of either human or chicken erythrocytes. This result is consistent with the drug sensitivity of the effects of agglutination upon chicken erythrocytes, since human erythrocytes and isolated membranes lack microtubule-like structures."}
{"id": "PMID:185617", "title": "An approach to the targeted attachment of peptides and proteins to solid supports.", "content": "A novel approach to affinity columns is described that is based on the high avidity of biotinylated molecules for avidin attached to solid supports. Biocytin amide [Nepsilon-(+)-biotinyllysine amide] was coupled to the COOH-terminal carboxyl group of corticotropin(1-24) [ACTH(1-24)] to form [biocytin25]ACTH(1-25) amide. The ability of this peptide to stimulate steroidogenesis of bovine adrenocortical cells was within experimental error identical to that of ACTH(1-24). The peptide also binds to avidin and avidin-Sepharose, forming stable complexes. Thus, with biotin as the anchor, the adrenocorticotropically active segment of the ACTH molecule was attached to a solid support in a targeted manner. The general applicability of this principle for the attachment of peptides and proteins to solid supports is discussed.", "contents": "An approach to the targeted attachment of peptides and proteins to solid supports. A novel approach to affinity columns is described that is based on the high avidity of biotinylated molecules for avidin attached to solid supports. Biocytin amide [Nepsilon-(+)-biotinyllysine amide] was coupled to the COOH-terminal carboxyl group of corticotropin(1-24) [ACTH(1-24)] to form [biocytin25]ACTH(1-25) amide. The ability of this peptide to stimulate steroidogenesis of bovine adrenocortical cells was within experimental error identical to that of ACTH(1-24). The peptide also binds to avidin and avidin-Sepharose, forming stable complexes. Thus, with biotin as the anchor, the adrenocorticotropically active segment of the ACTH molecule was attached to a solid support in a targeted manner. The general applicability of this principle for the attachment of peptides and proteins to solid supports is discussed."}
{"id": "PMID:185618", "title": "Partial purification and characterization of the mRNA for rat preproinsulin.", "content": "Electrophoretically homogeneous messenger RNA for rat preproinsulin has been prepared from an islet cell tumor by the use of oligo(dT(-cellulose chromatography and sucrose density gradient centrifugation. The molecular weight of the mRNA is about 210,000, as determined by polyacrylamide gel electrophoresis in formamide, and its sedimentation coefficient is 9.3 S in sucrose gradients containing 0.2 M NaCl. These results indicate that the synthesis of preproinsulin is directed by a monocistronic mRNA 600 nucleotides in length and requires approximately 55% of the molecule's coding capacity.", "contents": "Partial purification and characterization of the mRNA for rat preproinsulin. Electrophoretically homogeneous messenger RNA for rat preproinsulin has been prepared from an islet cell tumor by the use of oligo(dT(-cellulose chromatography and sucrose density gradient centrifugation. The molecular weight of the mRNA is about 210,000, as determined by polyacrylamide gel electrophoresis in formamide, and its sedimentation coefficient is 9.3 S in sucrose gradients containing 0.2 M NaCl. These results indicate that the synthesis of preproinsulin is directed by a monocistronic mRNA 600 nucleotides in length and requires approximately 55% of the molecule's coding capacity."}
{"id": "PMID:185619", "title": "On the specificity of synapse formation.", "content": "Clonal neuroblastome X glioma hybrid cells form synapses with striated muscle cells from different muscles and from different organisms, such as chick, mouse, and rat. Under appropriate conditions 65-80% of the muscle cells exhibited synaptic responses. The results indicate that most striated muscle cells have the same specificity for synapse formation and suggest that synaptogenesis is not dependent on interactions between complementary molecules on neuron and muscle cells that code for different synaptic connections.", "contents": "On the specificity of synapse formation. Clonal neuroblastome X glioma hybrid cells form synapses with striated muscle cells from different muscles and from different organisms, such as chick, mouse, and rat. Under appropriate conditions 65-80% of the muscle cells exhibited synaptic responses. The results indicate that most striated muscle cells have the same specificity for synapse formation and suggest that synaptogenesis is not dependent on interactions between complementary molecules on neuron and muscle cells that code for different synaptic connections."}
{"id": "PMID:185620", "title": "Reversion from transformed to normal phenotype by inhibition of protein synthesis in rat kidney cells infected with a temperature-sensitive mutant of Rous sarcoma virus.", "content": "By the use of a rat kidney cell line infected with a temperature-sensitive Rous sarcoma virus, we have shown that, at permissive temperatures where the cells are transformed, concanavalin A induces a clustering of its cell membrane receptors into patches, and the intracellular smooth muscle myosin-like protein is in a disordered state. By contrast, with infected cells grown at nonpermissive temperatures, the addition of concanavalin A does not alter the uniform distribution of its receptors, and the smooth muscle myosin-like protein is arranged in an ordered filamentous structure. These results are consistent with the hypothesis that the myosin protein is part of an intracellular aggregating-disaggregating complex. In the normal cell it is in its aggregated state and inhibits the lateral mobility of the concanavalin A receptors in the membrane; in the transformed cell the complex is relatively disaggregated and permits the concanavalin A receptors to be mobile. The addition of protein synthesis inhibitors to infected cells grown at the permissive temperature causes the cell to change from the transformed phenotype to the normal. Removal of the reversible inhibitors causes the cells to revert to the transformed phenotype. These results show that (i) protein synthesis, presumably of an unstable product of the transforming gene of the temperature-sensitive virus, is required to maintain the transformed state in these infected cells at the permissive temperature; and (ii) protein synthesis is not required for the intracellular myosin-containing complex to revert from its disordered transformed state to its ordered normal state. This suggests that the product of the transforming gene directly or indirectly causes the disaggregation of the myosin-containing complex in the process of transformation.", "contents": "Reversion from transformed to normal phenotype by inhibition of protein synthesis in rat kidney cells infected with a temperature-sensitive mutant of Rous sarcoma virus. By the use of a rat kidney cell line infected with a temperature-sensitive Rous sarcoma virus, we have shown that, at permissive temperatures where the cells are transformed, concanavalin A induces a clustering of its cell membrane receptors into patches, and the intracellular smooth muscle myosin-like protein is in a disordered state. By contrast, with infected cells grown at nonpermissive temperatures, the addition of concanavalin A does not alter the uniform distribution of its receptors, and the smooth muscle myosin-like protein is arranged in an ordered filamentous structure. These results are consistent with the hypothesis that the myosin protein is part of an intracellular aggregating-disaggregating complex. In the normal cell it is in its aggregated state and inhibits the lateral mobility of the concanavalin A receptors in the membrane; in the transformed cell the complex is relatively disaggregated and permits the concanavalin A receptors to be mobile. The addition of protein synthesis inhibitors to infected cells grown at the permissive temperature causes the cell to change from the transformed phenotype to the normal. Removal of the reversible inhibitors causes the cells to revert to the transformed phenotype. These results show that (i) protein synthesis, presumably of an unstable product of the transforming gene of the temperature-sensitive virus, is required to maintain the transformed state in these infected cells at the permissive temperature; and (ii) protein synthesis is not required for the intracellular myosin-containing complex to revert from its disordered transformed state to its ordered normal state. This suggests that the product of the transforming gene directly or indirectly causes the disaggregation of the myosin-containing complex in the process of transformation."}
{"id": "PMID:185621", "title": "Rous-sarcoma-virus-transformed fibroblasts having low levels of plasminogen activator.", "content": "Several clones of transformed chick embryo fibroblasts infected with wild-type B77-C or Prague-C strain of Rous sarcoma virus have been isolated from soft agar suspension. These clones were screened for plasminogen activator activity by overlaying monolayer cultures with medium containing agar, casein, and chicken plasminogen. Twenty-three percent of all of the isolated clones showed little caseinolytic activity, 42% had intermediate activity, and 35% had high activity. Although the clones with low plasminogen activator activity had no more than twice the activity shown by uninfected fibroblasts, they did not differ significantly from clones possessing high levels of plasminogen activator in their morphology, 2-deoxyglucose transport, or efficiency of colony formation in soft-agar.", "contents": "Rous-sarcoma-virus-transformed fibroblasts having low levels of plasminogen activator. Several clones of transformed chick embryo fibroblasts infected with wild-type B77-C or Prague-C strain of Rous sarcoma virus have been isolated from soft agar suspension. These clones were screened for plasminogen activator activity by overlaying monolayer cultures with medium containing agar, casein, and chicken plasminogen. Twenty-three percent of all of the isolated clones showed little caseinolytic activity, 42% had intermediate activity, and 35% had high activity. Although the clones with low plasminogen activator activity had no more than twice the activity shown by uninfected fibroblasts, they did not differ significantly from clones possessing high levels of plasminogen activator in their morphology, 2-deoxyglucose transport, or efficiency of colony formation in soft-agar."}
{"id": "PMID:185623", "title": "Nucleotide sequences in mouse DNA and RNA specific for Moloney sarcoma virus.", "content": "Complementary DNA (cDNA) synthesized by Moloney murine sarcoma virus (M-MSV) was separated into two parts, the first, termed MSV-specific cDNA, composed of nucleotide sequences found only in M-MSV viral RNA, and the second, termed MSV-MuLV common cDNA, composed of nucleotide sequences that were found in both M-MSV and murine leukemia virus (MuLV) VIRAL RNAs. RNA complementary to the MSV-specific cDNA was not found in several other MSV isolates, nor in ecotropic MuLV, mouse mammary tumor virus, or several murine xenotropic oncoviruses. Cellular DNA of several species was examined for the presence of nucleotide sequences complementary to MSV-specific cDNA. Cells transformed by M-MSV did contain MSV-specific cDNA in their DNA. Normal mouse cell DNA apparently contained the majority of MSV-specific nucleotide sequences. Cellular DNA of related species contained proportionally less MSV-specific cDNA. Hybrids of MSV-spedivic cDNA and cellular DNA of related species melted at lower temperatures than hybrids of MSV-specific cDNA and mouse cellular DNA. RNA from normal mouse adult or embryonic cells did not contain detectable nucleotide sequences complementary to MSV-specific cDNA. Transformation of cells with M-msv resulted in transcription of RNA hybridizing with MSV-specific cDNA. Methylcholanthrene-induced mouse sarcomas and cell lines derived from them did not contain RNA complementary to MSV-specific cDNA. Mouse cell lines transformed with avian sarcoma virus or Kirsten MSV-specific cDNA. RNA homologous to MSV-specific nucleotide sequences is measurably present only in cells transformed by M-MSV and not in cells transformed by other biological or chemical agents that also cause sarcomas.", "contents": "Nucleotide sequences in mouse DNA and RNA specific for Moloney sarcoma virus. Complementary DNA (cDNA) synthesized by Moloney murine sarcoma virus (M-MSV) was separated into two parts, the first, termed MSV-specific cDNA, composed of nucleotide sequences found only in M-MSV viral RNA, and the second, termed MSV-MuLV common cDNA, composed of nucleotide sequences that were found in both M-MSV and murine leukemia virus (MuLV) VIRAL RNAs. RNA complementary to the MSV-specific cDNA was not found in several other MSV isolates, nor in ecotropic MuLV, mouse mammary tumor virus, or several murine xenotropic oncoviruses. Cellular DNA of several species was examined for the presence of nucleotide sequences complementary to MSV-specific cDNA. Cells transformed by M-MSV did contain MSV-specific cDNA in their DNA. Normal mouse cell DNA apparently contained the majority of MSV-specific nucleotide sequences. Cellular DNA of related species contained proportionally less MSV-specific cDNA. Hybrids of MSV-spedivic cDNA and cellular DNA of related species melted at lower temperatures than hybrids of MSV-specific cDNA and mouse cellular DNA. RNA from normal mouse adult or embryonic cells did not contain detectable nucleotide sequences complementary to MSV-specific cDNA. Transformation of cells with M-msv resulted in transcription of RNA hybridizing with MSV-specific cDNA. Methylcholanthrene-induced mouse sarcomas and cell lines derived from them did not contain RNA complementary to MSV-specific cDNA. Mouse cell lines transformed with avian sarcoma virus or Kirsten MSV-specific cDNA. RNA homologous to MSV-specific nucleotide sequences is measurably present only in cells transformed by M-MSV and not in cells transformed by other biological or chemical agents that also cause sarcomas."}
{"id": "PMID:185622", "title": "Cellular cholesterol ester accumulation induced by free cholesterol-rich lipid dispersions.", "content": "The influence of lipoprotein composition on free cholesterol (RC) esterification and accumulation of esterified cholesterol (EC) was studied in cells of Fu5AH rat hepatoma exposed to culture media supplemented with (FC/P) ranging from 0.6 to 2.8. In the presence of normal human serum, FC-lecithin dispersions witb a FC/P greater than one stimulated both the esterification of FC and the accumulation of cellular EC. Conversely, dispersions with FC/P values of approximately one had no effect on either FC esterification or the accumulation of EC when compared to cells grown in the absence of lipid dispersions. No stimulation of cellular response was obtained when FC-rich dispersions were added to cells in the absence of serum; however, stimulation was observed when cells were exposed to isolated human serum lipoproteins (very low density, low density, and high density). With each lipoprotein, FC-lecithin dispersions with FC/P values less than one inhibited cholesteryl ester accumulation, FC-rich dispersions stimulated, and dispersions with FC/P values of approximately one had an effect equivalent to that of isolated lipproteins alone. These studies extablish that cellular FC esterification and EC content are not influenced solely by the FC concentration of medium, but rather respond to the ratio of FC to phospholipidl These studies also suggest that serum lipoproteins participate in the transfer of FC carried by FC-rich lecithin dispersions to cells.", "contents": "Cellular cholesterol ester accumulation induced by free cholesterol-rich lipid dispersions. The influence of lipoprotein composition on free cholesterol (RC) esterification and accumulation of esterified cholesterol (EC) was studied in cells of Fu5AH rat hepatoma exposed to culture media supplemented with (FC/P) ranging from 0.6 to 2.8. In the presence of normal human serum, FC-lecithin dispersions witb a FC/P greater than one stimulated both the esterification of FC and the accumulation of cellular EC. Conversely, dispersions with FC/P values of approximately one had no effect on either FC esterification or the accumulation of EC when compared to cells grown in the absence of lipid dispersions. No stimulation of cellular response was obtained when FC-rich dispersions were added to cells in the absence of serum; however, stimulation was observed when cells were exposed to isolated human serum lipoproteins (very low density, low density, and high density). With each lipoprotein, FC-lecithin dispersions with FC/P values less than one inhibited cholesteryl ester accumulation, FC-rich dispersions stimulated, and dispersions with FC/P values of approximately one had an effect equivalent to that of isolated lipproteins alone. These studies extablish that cellular FC esterification and EC content are not influenced solely by the FC concentration of medium, but rather respond to the ratio of FC to phospholipidl These studies also suggest that serum lipoproteins participate in the transfer of FC carried by FC-rich lecithin dispersions to cells."}
{"id": "PMID:185624", "title": "C-type virus particle formation in erythroblastic islands in spleens of C3Hf mice injected with erythropoietin.", "content": "Previous studies suggested a possible association between C-type virus particle formation and erythropoiesis. In this experiment, normal C3Hf mice were injected with erythropoietin in order to increase the rate of erythropoiesis. Sections of spleen from these animals revealed extensive areas of erythroblasts. C-type particles, budding from erythroblasts, were often observed in such areas of spleen from every mouse injected with erythropoietin. In contrast, in sections of spleen from control mice, zones of erythropoiesis were limited, and only a few scattered C-type virus particles were observed in some of the animals examined.", "contents": "C-type virus particle formation in erythroblastic islands in spleens of C3Hf mice injected with erythropoietin. Previous studies suggested a possible association between C-type virus particle formation and erythropoiesis. In this experiment, normal C3Hf mice were injected with erythropoietin in order to increase the rate of erythropoiesis. Sections of spleen from these animals revealed extensive areas of erythroblasts. C-type particles, budding from erythroblasts, were often observed in such areas of spleen from every mouse injected with erythropoietin. In contrast, in sections of spleen from control mice, zones of erythropoiesis were limited, and only a few scattered C-type virus particles were observed in some of the animals examined."}
{"id": "PMID:185625", "title": "Replication of murine leukemia virus in bone marrow-derived lymphocytes.", "content": "Murine lymphoid cells were infected in vitro with WN 1802 B, a naturally occurring murine leukemia virus isolated from the spleen of an 18-month-old BALB/c mouse. Normal spleen and bone marrow cells were more susceptible to infection than were cells prepared from thymus and lymph node. Spleen cells from athymic nu/nu mice also could be readily infected with virus. Permissive cells did not ingest iron readily infected with virus. Permissive cells did not ingest iron filings and did not adhere to plastic. Exogenous replication of murine leukemia virus was enhanced in spleen and lymph node cells treated with lipopolysaccharide, a bone marrow-derived lymphocyte mitogen. Conversely, cells treated with the thymus-derived lymphocyte cell mitogens, phytohemagglutinin and concanavalin A, were less capable of supporting murine leukemia virus replication. These studies suggest that the natural host for WN 1802 B is the bone marrow-derived lymphocyte.", "contents": "Replication of murine leukemia virus in bone marrow-derived lymphocytes. Murine lymphoid cells were infected in vitro with WN 1802 B, a naturally occurring murine leukemia virus isolated from the spleen of an 18-month-old BALB/c mouse. Normal spleen and bone marrow cells were more susceptible to infection than were cells prepared from thymus and lymph node. Spleen cells from athymic nu/nu mice also could be readily infected with virus. Permissive cells did not ingest iron readily infected with virus. Permissive cells did not ingest iron filings and did not adhere to plastic. Exogenous replication of murine leukemia virus was enhanced in spleen and lymph node cells treated with lipopolysaccharide, a bone marrow-derived lymphocyte mitogen. Conversely, cells treated with the thymus-derived lymphocyte cell mitogens, phytohemagglutinin and concanavalin A, were less capable of supporting murine leukemia virus replication. These studies suggest that the natural host for WN 1802 B is the bone marrow-derived lymphocyte."}
{"id": "PMID:185626", "title": "Opiate receptor: autoradiographic localization in rat brain.", "content": "Opiate receptor sites in rat brain can be labeled in vivo by [3H]diprenorphine, a potent opiate antagoinst. Using techniques to minimize diffusion in fresh, frozen, unfixed brain, we have localized [3H]diprenorphine by autoradiography to visualize the distribution of opiate receptors. Silver grains indicative of the binding of labeled [3H]diprenorphine are discretely localized in numerous areas of the brain with very high densities in the locus coeruleus, the substantia gelatinosa of the spinal cord, and in clusters within the caudate-putamen, amygdala, and parts of the periventricular gray matter.", "contents": "Opiate receptor: autoradiographic localization in rat brain. Opiate receptor sites in rat brain can be labeled in vivo by [3H]diprenorphine, a potent opiate antagoinst. Using techniques to minimize diffusion in fresh, frozen, unfixed brain, we have localized [3H]diprenorphine by autoradiography to visualize the distribution of opiate receptors. Silver grains indicative of the binding of labeled [3H]diprenorphine are discretely localized in numerous areas of the brain with very high densities in the locus coeruleus, the substantia gelatinosa of the spinal cord, and in clusters within the caudate-putamen, amygdala, and parts of the periventricular gray matter."}
{"id": "PMID:185630", "title": "Neurobiological Considerations of the mode of action of lithium carbonate in the treatment of affective disorders?", "content": "The effects of lithium on membrane function and cellular processes are considered in relation to lithium's physiochemical properties. Several cellular regulatory functions, including cyclic AMP formation and metabolism and biogenic amine neurotransmitter metabolism, are examined as possible mechanisms whereby lithium might exert its mood stabilizing actions. The necessity for understanding lithium's interactions with \"receptors\" - the molecular sites affected by lithium - in considering its pre-and post-synapatic effects in stressed.", "contents": "Neurobiological Considerations of the mode of action of lithium carbonate in the treatment of affective disorders? The effects of lithium on membrane function and cellular processes are considered in relation to lithium's physiochemical properties. Several cellular regulatory functions, including cyclic AMP formation and metabolism and biogenic amine neurotransmitter metabolism, are examined as possible mechanisms whereby lithium might exert its mood stabilizing actions. The necessity for understanding lithium's interactions with \"receptors\" - the molecular sites affected by lithium - in considering its pre-and post-synapatic effects in stressed."}
{"id": "PMID:185633", "title": "Role of cyclic nucleotides in cell growth and differentiation.", "content": "A simple model is depicted below that suggests some unifying principals in the action of cyclic nucleotides in the GO-to-G+ interconversion, differentiation, and transformation (see article). The letters with G+ subscripts (AG+ through EG+) represent cell states at different increasing levels of \"determination\" (see sect. vE). Cells in each of these states are continuously reproducing themselves through cell division (i.e., they are in G+). As an alternative to cell reporduction, cells at each level may move toward or enter GO, which is conceived of not only as a quiescent state but also as a state in which differentiated properties are more fully expressed. This state is designated by letters with GO subscripts (AGO through EGO). Entrance into this more expressed state will usually be reversible (nerve cells and red blood cells are two exceptions). Sometimes movement toward GO and full expression may require a number of cell divisions. Ultimately, however, there usually will be a slowing or cessation of cell division. The transformed state, according to this model, is one in which cells have lost the ability to enter the \"expressed\" CO state. However, they do remain differentiated in the sense that they have maintained their level of determination and can be induced to enter into the expressed state, as for example in the case of DBcAMP treatment of transformed fibroblasts. In most cases, cAMP appears to stimulate cells to proceed toward XGO (where X = A,B,C,D, or E) and toward fuller expression of their differentiated functions. It is not the sole mediator of this transition. In cell types where cAMP plays this role, transformation may arise through a defect in the ability to raise cAMP levels in response to growth-regulatory signals or in a defect in the cell's ability to respond to cAMP. In other cell types, cAMP may not be involved in the CO-to-C+ transition or may act in the opposite direction (see sect. II). It remains to be seen whether these situations are ture exceptions or whether different loci of regulation are involved. For example it is possible that in certain cases where cAMP has been shown to stimulate growth that it is stimulating growth toward a more expressed state. Other actions of cAMP relating to cell-cycle traverse have been discussed (sect. III). Investigations of the action of cGMP are still at a preliminary stage of development. There is evidence consistent with the idea that cGMP mediates conversion toward the G+ state in some cell types (see sect. II) under certain conditions. However, further studies are required to establish this as a fact. There has been little or no reported evidence relating to a role for cGMP in expression of differentiated properties, nor has there been any significant evidence as yet for other cell-cycle roles of cGMP. It should be apparent that the areas of biology covered in this review are only beginning to evolve biochemically...", "contents": "Role of cyclic nucleotides in cell growth and differentiation. A simple model is depicted below that suggests some unifying principals in the action of cyclic nucleotides in the GO-to-G+ interconversion, differentiation, and transformation (see article). The letters with G+ subscripts (AG+ through EG+) represent cell states at different increasing levels of \"determination\" (see sect. vE). Cells in each of these states are continuously reproducing themselves through cell division (i.e., they are in G+). As an alternative to cell reporduction, cells at each level may move toward or enter GO, which is conceived of not only as a quiescent state but also as a state in which differentiated properties are more fully expressed. This state is designated by letters with GO subscripts (AGO through EGO). Entrance into this more expressed state will usually be reversible (nerve cells and red blood cells are two exceptions). Sometimes movement toward GO and full expression may require a number of cell divisions. Ultimately, however, there usually will be a slowing or cessation of cell division. The transformed state, according to this model, is one in which cells have lost the ability to enter the \"expressed\" CO state. However, they do remain differentiated in the sense that they have maintained their level of determination and can be induced to enter into the expressed state, as for example in the case of DBcAMP treatment of transformed fibroblasts. In most cases, cAMP appears to stimulate cells to proceed toward XGO (where X = A,B,C,D, or E) and toward fuller expression of their differentiated functions. It is not the sole mediator of this transition. In cell types where cAMP plays this role, transformation may arise through a defect in the ability to raise cAMP levels in response to growth-regulatory signals or in a defect in the cell's ability to respond to cAMP. In other cell types, cAMP may not be involved in the CO-to-C+ transition or may act in the opposite direction (see sect. II). It remains to be seen whether these situations are ture exceptions or whether different loci of regulation are involved. For example it is possible that in certain cases where cAMP has been shown to stimulate growth that it is stimulating growth toward a more expressed state. Other actions of cAMP relating to cell-cycle traverse have been discussed (sect. III). Investigations of the action of cGMP are still at a preliminary stage of development. There is evidence consistent with the idea that cGMP mediates conversion toward the G+ state in some cell types (see sect. II) under certain conditions. However, further studies are required to establish this as a fact. There has been little or no reported evidence relating to a role for cGMP in expression of differentiated properties, nor has there been any significant evidence as yet for other cell-cycle roles of cGMP. It should be apparent that the areas of biology covered in this review are only beginning to evolve biochemically..."}
{"id": "PMID:185635", "title": "Aspects of smooth muscle function in molluscan catch muscle.", "content": "1) Catch in Mytilus ABRM may be a specialization of a mechanism common to all muscles that gives rise to stretch resistance in the resting state. Catch appears to be due to actin myosin interaction. Since this interaction is regulated by nerves, it provides a convenient model for studying resting stretch resistance. 2) Studies of the structure of Mytilus ABRM revela two types of intercellular connections: a) direct connections between muscle fibers [these nexal (gap) junctions interconnect the muscle cells electrically]; b) muscle fiber-collagen-muscle fiber connections [these provide mechanical connections between muscle cells via collagen fibers]. The structure of Mytilus ABRM supports speculation that smooth muscle filaments are organized into contractile units. 3) A rise in cAMP levels occurs in response to the relaxing transmitter, serotonin. It is not certain whether the cAMP system directly controls the ability of the contractile proteins to interact or whether it regulates intracellular levels of Ca2+. 4) Calcium ions in activation are derived from two sources: an internal source, probably the sarcoplasmic reticulum, and an external source, across the muscle membrane. 5) The nature of catch remains in question, although most evidence favors the linkage hypothesis.", "contents": "Aspects of smooth muscle function in molluscan catch muscle. 1) Catch in Mytilus ABRM may be a specialization of a mechanism common to all muscles that gives rise to stretch resistance in the resting state. Catch appears to be due to actin myosin interaction. Since this interaction is regulated by nerves, it provides a convenient model for studying resting stretch resistance. 2) Studies of the structure of Mytilus ABRM revela two types of intercellular connections: a) direct connections between muscle fibers [these nexal (gap) junctions interconnect the muscle cells electrically]; b) muscle fiber-collagen-muscle fiber connections [these provide mechanical connections between muscle cells via collagen fibers]. The structure of Mytilus ABRM supports speculation that smooth muscle filaments are organized into contractile units. 3) A rise in cAMP levels occurs in response to the relaxing transmitter, serotonin. It is not certain whether the cAMP system directly controls the ability of the contractile proteins to interact or whether it regulates intracellular levels of Ca2+. 4) Calcium ions in activation are derived from two sources: an internal source, probably the sarcoplasmic reticulum, and an external source, across the muscle membrane. 5) The nature of catch remains in question, although most evidence favors the linkage hypothesis."}
{"id": "PMID:185636", "title": "The effect of ACTH and diazepam on the uptake of tritiated uridine into brain, muscles and liver of infant rats.", "content": "In 2-day-old rats, ACTH increases the uptake of 3H-uridine in the brain; no such effects were observed in the msucle and liver tissue. Diazepam does not affect the uptake of 3H-uridine into the brain tissue, but decreases the uptake into the muscle tissue. In the brain tissue of infant rats, ACTH does not change the distribution of radioactivity of intraperitoneally administered 3H-uridine among U, Urd, UMP, UDP and UTP. Diazepam increases the amount of radioactivity, found at the U spot. In the muscle, both ACTH and Diazepam increases the amount of radioactivities found in the Urd spot. A significant correlation between the radioactivity of UMP+UDP+UTP and the specific activity of RNA was proved only in the brain. The ratio: specific activity of brain RNA/radioactivity of UMP+UDP+UTP was thus used as a tentative indicator of the biosynthesis of brain RNA. Neither ACTH nor diazepam altered this ratio in infant rats.", "contents": "The effect of ACTH and diazepam on the uptake of tritiated uridine into brain, muscles and liver of infant rats. In 2-day-old rats, ACTH increases the uptake of 3H-uridine in the brain; no such effects were observed in the msucle and liver tissue. Diazepam does not affect the uptake of 3H-uridine into the brain tissue, but decreases the uptake into the muscle tissue. In the brain tissue of infant rats, ACTH does not change the distribution of radioactivity of intraperitoneally administered 3H-uridine among U, Urd, UMP, UDP and UTP. Diazepam increases the amount of radioactivity, found at the U spot. In the muscle, both ACTH and Diazepam increases the amount of radioactivities found in the Urd spot. A significant correlation between the radioactivity of UMP+UDP+UTP and the specific activity of RNA was proved only in the brain. The ratio: specific activity of brain RNA/radioactivity of UMP+UDP+UTP was thus used as a tentative indicator of the biosynthesis of brain RNA. Neither ACTH nor diazepam altered this ratio in infant rats."}
{"id": "PMID:185637", "title": "Interaction of histones with human serum proteins.", "content": "The authors describe the interactions of whole calf thymus histone and its fractions with the human serum proteins. Immunoelectrophoretic analysis revealed two types of interactions: 1) a decrease in the electrophoretic mobility of a whole, immunochemically uniform fraction, and 2) a decrease in the electrophoretic mobility of only some molecules of such a fraction. In this association, the arginine-rich histone fraction (F3) was found to be the most active. The findings are important for interpreting the results of biological treatments.", "contents": "Interaction of histones with human serum proteins. The authors describe the interactions of whole calf thymus histone and its fractions with the human serum proteins. Immunoelectrophoretic analysis revealed two types of interactions: 1) a decrease in the electrophoretic mobility of a whole, immunochemically uniform fraction, and 2) a decrease in the electrophoretic mobility of only some molecules of such a fraction. In this association, the arginine-rich histone fraction (F3) was found to be the most active. The findings are important for interpreting the results of biological treatments."}
{"id": "PMID:185638", "title": "An operation for syndactyly, and its results.", "content": "We describe our method of operation for syndactyly repair and our results in 62 patients (74 hands, 143 commissures), all treated more than two years ago. The operation was performed on patients aged from 17 months to two years (except those with acrosyndactyly). Postoperative web formation was not seen in any of these patients.", "contents": "An operation for syndactyly, and its results. We describe our method of operation for syndactyly repair and our results in 62 patients (74 hands, 143 commissures), all treated more than two years ago. The operation was performed on patients aged from 17 months to two years (except those with acrosyndactyly). Postoperative web formation was not seen in any of these patients."}
{"id": "PMID:185645", "title": "Small-cell carcinoma of the lung. Cytological, roentgenologic, and clinical findings in a consecutive series diagnosed by fine-needle aspiration biopsy.", "content": "Small-cell anaplastic carcinoma was diagnosed cytologically in 54 of 2,726 consecutive transthoracic fine-needle aspiration biopsies. Histological material was available in 31 cases (28 anaplastic small-cell carcinomas, 1 carcinoid tumor, 1 adenocarcinoma, and 1 reticulum-cell sarcoma). Fine-needle aspiration cytology is reliable enough to permit a definite diagnosis of small-cell carcinoma, especially when combined with the roentgenograms and clinical findings.", "contents": "Small-cell carcinoma of the lung. Cytological, roentgenologic, and clinical findings in a consecutive series diagnosed by fine-needle aspiration biopsy. Small-cell anaplastic carcinoma was diagnosed cytologically in 54 of 2,726 consecutive transthoracic fine-needle aspiration biopsies. Histological material was available in 31 cases (28 anaplastic small-cell carcinomas, 1 carcinoid tumor, 1 adenocarcinoma, and 1 reticulum-cell sarcoma). Fine-needle aspiration cytology is reliable enough to permit a definite diagnosis of small-cell carcinoma, especially when combined with the roentgenograms and clinical findings."}
{"id": "PMID:185646", "title": "Evaluation of radiopharmaceuticals for the detection of acute myocardial infarction in man.", "content": "The accuracy of the scintigraphic diagnosis of acute myocardial infarction with 99mTc-pyrophosphate, 99mTc-tetracycline and 99mTc-glucoheptonate was assessed in 63 patients, 43 of whom had clinical evidence of acute myocardial infarction. In 15, studies with both 99mTc-tetracycline and 99mTc-pyrophosphate were performed. Accuracy was greatest with 99mTc-pyrophosphate (17/17 true positives, 8/10 true negatives) contrasted with 99mTc-tetracycline (12/25 true positives, 6/11 true negatives) and 99mTc-glucoheptonate (3/13 true positives, 2/2 true negatives). 99mTc-pyrophosphate was the most sensitive tracer for the detection of acute myocardial infarction. The diagnostic accuracy with 99mTc-glucoheptonate was poor.", "contents": "Evaluation of radiopharmaceuticals for the detection of acute myocardial infarction in man. The accuracy of the scintigraphic diagnosis of acute myocardial infarction with 99mTc-pyrophosphate, 99mTc-tetracycline and 99mTc-glucoheptonate was assessed in 63 patients, 43 of whom had clinical evidence of acute myocardial infarction. In 15, studies with both 99mTc-tetracycline and 99mTc-pyrophosphate were performed. Accuracy was greatest with 99mTc-pyrophosphate (17/17 true positives, 8/10 true negatives) contrasted with 99mTc-tetracycline (12/25 true positives, 6/11 true negatives) and 99mTc-glucoheptonate (3/13 true positives, 2/2 true negatives). 99mTc-pyrophosphate was the most sensitive tracer for the detection of acute myocardial infarction. The diagnostic accuracy with 99mTc-glucoheptonate was poor."}
{"id": "PMID:185647", "title": "AG 60.99: A promising contrast agent for computed tomography of the liver and spleen.", "content": "AG 60.99, an emulsion of poppy-seed oil, is proposed as a promising organ-specific agent for computed tomography (CT) of the liver and spleen. This agent not only opacifies the hepatic parenchyma enough to enhance visualization of the bile ducts but also demonstrates the vascular anatomy with smaller doses than those required for conventional studies.", "contents": "AG 60.99: A promising contrast agent for computed tomography of the liver and spleen. AG 60.99, an emulsion of poppy-seed oil, is proposed as a promising organ-specific agent for computed tomography (CT) of the liver and spleen. This agent not only opacifies the hepatic parenchyma enough to enhance visualization of the bile ducts but also demonstrates the vascular anatomy with smaller doses than those required for conventional studies."}
{"id": "PMID:185648", "title": "Angiographic features of malignant fibrous histiocytomas.", "content": "The angiographic findings in 2 cases of metastatic fibrous histiocytoma are discussed. A lesion in the brain was completely avascular and displaced the surrounding vessels, whereas the renal lesions were hypovascular, usually well demarcated, sometimes exhibited beak formation, and demonstrated fine, corkscrew-like tumor vessels with delayed emptying but no tumor blush or early draining veins.", "contents": "Angiographic features of malignant fibrous histiocytomas. The angiographic findings in 2 cases of metastatic fibrous histiocytoma are discussed. A lesion in the brain was completely avascular and displaced the surrounding vessels, whereas the renal lesions were hypovascular, usually well demarcated, sometimes exhibited beak formation, and demonstrated fine, corkscrew-like tumor vessels with delayed emptying but no tumor blush or early draining veins."}
{"id": "PMID:185649", "title": "Adhesive arachnoiditis following lumbar radiculography with water-soluble contrast agents. A clinical report with special reference to metrizamide.", "content": "The frequency of adhesive arachnoiditis following lumbar radiculography with methiodal sodium (95 patients), methylglucamine iocarmate (20 examinations in 18 patients), and metrizamide (77 examinations in 73 patients) was found to be 29% in patients who were not operated on between methiodal studies and 48% in those who were operated on. With both methylglucamine iocarmate and metrizamide the frequency was very low. No changes indicating adhesive arachnoiditis were seen with these media in patients who were not operated on between radiographic examinations.", "contents": "Adhesive arachnoiditis following lumbar radiculography with water-soluble contrast agents. A clinical report with special reference to metrizamide. The frequency of adhesive arachnoiditis following lumbar radiculography with methiodal sodium (95 patients), methylglucamine iocarmate (20 examinations in 18 patients), and metrizamide (77 examinations in 73 patients) was found to be 29% in patients who were not operated on between methiodal studies and 48% in those who were operated on. With both methylglucamine iocarmate and metrizamide the frequency was very low. No changes indicating adhesive arachnoiditis were seen with these media in patients who were not operated on between radiographic examinations."}
{"id": "PMID:185650", "title": "Radionuclide angiography in evaluation of chemodectomas of the jugular glomus.", "content": "Clinical, radiographic, and radionuclide angiographic findings of three cases of jugular glomic tumor associated with hearing loss are discussed. In one case computed tomographic findings are discussed. It is concluded that radioisotopic techniques may be useful in diagnosis and follow-up of this tumor.", "contents": "Radionuclide angiography in evaluation of chemodectomas of the jugular glomus. Clinical, radiographic, and radionuclide angiographic findings of three cases of jugular glomic tumor associated with hearing loss are discussed. In one case computed tomographic findings are discussed. It is concluded that radioisotopic techniques may be useful in diagnosis and follow-up of this tumor."}
{"id": "PMID:185651", "title": "Observing the growth of Wilms' tumor.", "content": "Four children ranging in age from 2 1/2 months to 4 years had excretory urography initially for reasons other than evaluation of an abdominal mass. Three patients had repeat urography only after masses became apparent at intervals of 8.5 months, 9 months and 15 months after the initial urogram. The fourth patient was followed with interval excretory urography for urinary tract infection and a large renal mass was seen 13 months after the initial urogram. The results suggest that the present data on estimated rates of growth do not support the established theory of the rate of growth for Wilms' tumor.", "contents": "Observing the growth of Wilms' tumor. Four children ranging in age from 2 1/2 months to 4 years had excretory urography initially for reasons other than evaluation of an abdominal mass. Three patients had repeat urography only after masses became apparent at intervals of 8.5 months, 9 months and 15 months after the initial urogram. The fourth patient was followed with interval excretory urography for urinary tract infection and a large renal mass was seen 13 months after the initial urogram. The results suggest that the present data on estimated rates of growth do not support the established theory of the rate of growth for Wilms' tumor."}
{"id": "PMID:185660", "title": "Enzyme histochemistry of bone and cartilage cells.", "content": "Initial studies indicated that bone and cartilage, when treated with a hypertonic glutaraldehyde fixative for a short period, retained significant enzyme activity for histochemistry and also maintained excellent fine structure. We used 6% glutaraldehyde in 0.1 M cacodylate buffer, pH = 7.2, 4 degrees C to fix small pieces of bone or cartilage for three hours while the tissues were being constantly agitated. These samples were demineralized in 10% ethylene diamine tetraacetic acid, buffered to pH = 7.2 with 0.1 M Tris HC1, at 4 degrees C. The demineralized tissue was frozen and cryostat sections 32 microns thick were taken for incubation at 37 degrees C in various media for histochemistry. For electron microscopic localization of enzymes a heavy metal capturing method had to be used. For light microscopy, the azo dye methods were frequently used, but these were not usable for electron microscopy. Alkaline phosphatase was found on the outer surface of osteoblast and hypertrophic cartilage cell membranes. The only intracellular enzyme activity was found on the mitochondrial membranes of the osteoclast and only when the pH of the media was lowered from the optimum 9.5 to 8.5. Alkaline phosphatase was not found along the osteocyte or young cartilage cell membranes...", "contents": "Enzyme histochemistry of bone and cartilage cells. Initial studies indicated that bone and cartilage, when treated with a hypertonic glutaraldehyde fixative for a short period, retained significant enzyme activity for histochemistry and also maintained excellent fine structure. We used 6% glutaraldehyde in 0.1 M cacodylate buffer, pH = 7.2, 4 degrees C to fix small pieces of bone or cartilage for three hours while the tissues were being constantly agitated. These samples were demineralized in 10% ethylene diamine tetraacetic acid, buffered to pH = 7.2 with 0.1 M Tris HC1, at 4 degrees C. The demineralized tissue was frozen and cryostat sections 32 microns thick were taken for incubation at 37 degrees C in various media for histochemistry. For electron microscopic localization of enzymes a heavy metal capturing method had to be used. For light microscopy, the azo dye methods were frequently used, but these were not usable for electron microscopy. Alkaline phosphatase was found on the outer surface of osteoblast and hypertrophic cartilage cell membranes. The only intracellular enzyme activity was found on the mitochondrial membranes of the osteoclast and only when the pH of the media was lowered from the optimum 9.5 to 8.5. Alkaline phosphatase was not found along the osteocyte or young cartilage cell membranes..."}
{"id": "PMID:185661", "title": "Histochemical characteristics of vertebrate striated muscle: a review.", "content": "(1) The histochemical staining pattern of succinic dehydrogenase (SDH) does not show unequivocal differentiation between the type I red and type II red fibres in mammalian striated muscles. (2) Since high biochemical activity of beta-hydroxybutyric dehydrogenase (beta-HOBDH) occurs in mitochondria of the type I red fibres, the histochemical localization of this enzyme may show a pattern of staining reciprocal to that seen for myofibrillar ATPase. (3) It remains to be confirmed that the type I red fibres, which are possibly slow-twitch physiologically, possess the highest concentration of myoglobin. The histochemical correlation of myoglobin and myofibrillar ATPase in serial sections should be studied. (4) In order to achieve a more realistic picture, various glycolytic and glycogenolytic enzymes should be incubated according to the gelatin film technique, or semipermeable membrane technique or collagen polypeptide technique. A histochemical correlation of phosphorylase, LDH, PFK, alpha-glycerophosphate dehydrogenase, and myofibrillar ATPase in adjacent muscle sections may throw light on the histochemical characteristics of the different fibre-types. (5) The specific histochemical demonstration of AMPase is achieved following preincubation of tissue sections. (6) ADPase has been demonstrated by the calcium precipitation technique only (GUTH and YELLIN, 1971). A number of studies claim, however, that ADPase is not demonstrable histochemically in muscle fibres. (7) The presence of magnesium ions is a prerequisite for the adequate histochemical demonstration of mitochondrial ATPase. The latter is inhibited almost completely by 40 mM Ca++ (when Mg++ is not added) at both neutral and alkaline pH values. (8) The histochemical activity of SR-AT-Pase seen as continuous reticula but without punctuate and sub-sarcolemmal staining possibly represents the extra ATPase of SR. (9) On the basis of myofibrillar ATPase reaction, an inherent heterogeneity, between the type II red and type II white may be recognized. In addition, the above fibre-types possess their respective sub-populations. (10) Following diK+ EDTA preincubation, some type II red fibres show selective lability. These are the mitochondria-rich fibres. Thus in the total absence of both punctuate and subsarcolemmal staining, the presence of mitochondrial ATPase activity under the histochemical conditions for myofibrillar ATPase is unlikely. (11) The reaction pattern of CK/ATPase (coupled reaction) at pH 6.9 is distinctly intermyofibrillar and unlike SDH-pattern. This reticular reaction is associated mainly with the SR and hence the importance of transphosphorylation in this organelle for the Ca++ uptake and muscle relaxation. (12) The CK/ATPase reaction at pH8.0 has shown important histoenzymatic characteristics. At this pH value the type I red fibres and slow-twitch soleus show myofibrillar reaction pattern. This identical histochemical behaviour suggests that type I red fibres are possibly slow-contracting...", "contents": "Histochemical characteristics of vertebrate striated muscle: a review. (1) The histochemical staining pattern of succinic dehydrogenase (SDH) does not show unequivocal differentiation between the type I red and type II red fibres in mammalian striated muscles. (2) Since high biochemical activity of beta-hydroxybutyric dehydrogenase (beta-HOBDH) occurs in mitochondria of the type I red fibres, the histochemical localization of this enzyme may show a pattern of staining reciprocal to that seen for myofibrillar ATPase. (3) It remains to be confirmed that the type I red fibres, which are possibly slow-twitch physiologically, possess the highest concentration of myoglobin. The histochemical correlation of myoglobin and myofibrillar ATPase in serial sections should be studied. (4) In order to achieve a more realistic picture, various glycolytic and glycogenolytic enzymes should be incubated according to the gelatin film technique, or semipermeable membrane technique or collagen polypeptide technique. A histochemical correlation of phosphorylase, LDH, PFK, alpha-glycerophosphate dehydrogenase, and myofibrillar ATPase in adjacent muscle sections may throw light on the histochemical characteristics of the different fibre-types. (5) The specific histochemical demonstration of AMPase is achieved following preincubation of tissue sections. (6) ADPase has been demonstrated by the calcium precipitation technique only (GUTH and YELLIN, 1971). A number of studies claim, however, that ADPase is not demonstrable histochemically in muscle fibres. (7) The presence of magnesium ions is a prerequisite for the adequate histochemical demonstration of mitochondrial ATPase. The latter is inhibited almost completely by 40 mM Ca++ (when Mg++ is not added) at both neutral and alkaline pH values. (8) The histochemical activity of SR-AT-Pase seen as continuous reticula but without punctuate and sub-sarcolemmal staining possibly represents the extra ATPase of SR. (9) On the basis of myofibrillar ATPase reaction, an inherent heterogeneity, between the type II red and type II white may be recognized. In addition, the above fibre-types possess their respective sub-populations. (10) Following diK+ EDTA preincubation, some type II red fibres show selective lability. These are the mitochondria-rich fibres. Thus in the total absence of both punctuate and subsarcolemmal staining, the presence of mitochondrial ATPase activity under the histochemical conditions for myofibrillar ATPase is unlikely. (11) The reaction pattern of CK/ATPase (coupled reaction) at pH 6.9 is distinctly intermyofibrillar and unlike SDH-pattern. This reticular reaction is associated mainly with the SR and hence the importance of transphosphorylation in this organelle for the Ca++ uptake and muscle relaxation. (12) The CK/ATPase reaction at pH8.0 has shown important histoenzymatic characteristics. At this pH value the type I red fibres and slow-twitch soleus show myofibrillar reaction pattern. This identical histochemical behaviour suggests that type I red fibres are possibly slow-contracting..."}
{"id": "PMID:185667", "title": "Modification of the Warburg's flask for the study of electric current effect upon the activity of enzymatic systems.", "content": "Modifications of the Warburg's flask were suggested for the study of the electric current effect upon enzymatic systems under directly stimulation \"in vitro\" and \"in vivo\" conditions. The proposed modifications made on the Warburg's flask were basically constituted by the insertion of two platinum and mercury electrodes in the principal reservoir. In order to demonstrate the efficiency and viability of the suggested modification, one experience concerning the effect of the electric current upon the cerebral glutamate decarboxylase activity was shown. The apoenzyme substrate system was activated 1.81 times by the electrical stimulation in absence of the coenzyme. In a similar way the complete system, that is, the apoenzyme-coenzyme-substrate was also stimulated. The physical phenomena seem to be of importance for the understanding of the physiology and biochemistry of the nervous tissue.", "contents": "Modification of the Warburg's flask for the study of electric current effect upon the activity of enzymatic systems. Modifications of the Warburg's flask were suggested for the study of the electric current effect upon enzymatic systems under directly stimulation \"in vitro\" and \"in vivo\" conditions. The proposed modifications made on the Warburg's flask were basically constituted by the insertion of two platinum and mercury electrodes in the principal reservoir. In order to demonstrate the efficiency and viability of the suggested modification, one experience concerning the effect of the electric current upon the cerebral glutamate decarboxylase activity was shown. The apoenzyme substrate system was activated 1.81 times by the electrical stimulation in absence of the coenzyme. In a similar way the complete system, that is, the apoenzyme-coenzyme-substrate was also stimulated. The physical phenomena seem to be of importance for the understanding of the physiology and biochemistry of the nervous tissue."}
{"id": "PMID:185668", "title": "Inhibition of the glucose induced insulin release by somatostatin in the isolated perfused rat pancreas. Action of cyclic AMP, glucagon and glibenclamide.", "content": "Insulin release in the perfused isolated rat pancreas was measured after stimulation with 16.5 mM glucose with and without somatostatin (cycle form, 100 ng/ml) in the medium. A complete blockage of the typical biphasic pattern of insulin release ocurred with somatostatin in the medium. Such blockage was abolished when cAMP (2.5 mM) and a 0.5 ml solution of glucagon (1 mg/ml) were continuously perfused for 20-minute periods and for 30-second periods correspondently. It did not take place when glibenclamide (HB-419) was perfused for a 20-minute period at a rate of 10 mug/ml. The results suggest that the adenylcyclase dependent mechanisms of glucose-induced insulin release are involved in the inhibition of the glucose-induced insulin secretion by somatostatin.", "contents": "Inhibition of the glucose induced insulin release by somatostatin in the isolated perfused rat pancreas. Action of cyclic AMP, glucagon and glibenclamide. Insulin release in the perfused isolated rat pancreas was measured after stimulation with 16.5 mM glucose with and without somatostatin (cycle form, 100 ng/ml) in the medium. A complete blockage of the typical biphasic pattern of insulin release ocurred with somatostatin in the medium. Such blockage was abolished when cAMP (2.5 mM) and a 0.5 ml solution of glucagon (1 mg/ml) were continuously perfused for 20-minute periods and for 30-second periods correspondently. It did not take place when glibenclamide (HB-419) was perfused for a 20-minute period at a rate of 10 mug/ml. The results suggest that the adenylcyclase dependent mechanisms of glucose-induced insulin release are involved in the inhibition of the glucose-induced insulin secretion by somatostatin."}
{"id": "PMID:185669", "title": "Relationship between losses in cytochrome oxidase activity and peroxidation of monosaturated phosphatidylcholines and phosphatidylethanolamines.", "content": "Incubation of inner mitochondrial membranes from rat liver in the presence of inducers of peroxidation reactions, such as ascorbate or cysteine, produced a large loss in cytochrome oxidase activity parallel to the disappearance of phosphatidylcholine and phosphatidylethanolamine molecular species, which contained a saturated and an unsaturated fatty acid. The loss in enzyme activity was unrelated to alterations in other species of these phospholipids or other ones. These results may reflect the existence of specific associations within the membrane between cytochrome oxidase and monosaturated phosphatidylcholines and/or phosphatidylethanolamines.", "contents": "Relationship between losses in cytochrome oxidase activity and peroxidation of monosaturated phosphatidylcholines and phosphatidylethanolamines. Incubation of inner mitochondrial membranes from rat liver in the presence of inducers of peroxidation reactions, such as ascorbate or cysteine, produced a large loss in cytochrome oxidase activity parallel to the disappearance of phosphatidylcholine and phosphatidylethanolamine molecular species, which contained a saturated and an unsaturated fatty acid. The loss in enzyme activity was unrelated to alterations in other species of these phospholipids or other ones. These results may reflect the existence of specific associations within the membrane between cytochrome oxidase and monosaturated phosphatidylcholines and/or phosphatidylethanolamines."}
{"id": "PMID:185670", "title": "Mitochondrial DNA of Yoshida ascites tumour cells. Physicochemical properties and biological function.", "content": "Mitochondrial DNA from Yoshida A.H. 130 cells, has been characterized by determination of the buoyant density by CsCl equilibrium density gradient centrifugation and the thermal denaturation and renaturation behaviour. These studies have been carried out parallelly on nuclear DNA from the same cells in order to search for possible differences between both DNAs. Mitochondrial DNA of Yoshida cells presents an equilbrium in CsCl of 1.7154 g/cm3 and a sharp melting with a Tm of 92 degrees C. Nuclear DNA presents an equilibrium of 1.7030 g/cm3 and a Tm of 88 degrees C. The guanine plus cytosine content in both DNAs has been calculated from tumour results and compared with the content in normal rat liver cells M-DNA of tumour cells presents a higher guanine plus cytosine content than N-DNA, whereas in normal liver cells is higher in N-DNA. N-DNAs of both normal and tumour cells have the same guanine plus cytosine content, whereas M-DNA from tumour cells presents a significant increase (about 35%) with regard to this from normal liver cells.", "contents": "Mitochondrial DNA of Yoshida ascites tumour cells. Physicochemical properties and biological function. Mitochondrial DNA from Yoshida A.H. 130 cells, has been characterized by determination of the buoyant density by CsCl equilibrium density gradient centrifugation and the thermal denaturation and renaturation behaviour. These studies have been carried out parallelly on nuclear DNA from the same cells in order to search for possible differences between both DNAs. Mitochondrial DNA of Yoshida cells presents an equilbrium in CsCl of 1.7154 g/cm3 and a sharp melting with a Tm of 92 degrees C. Nuclear DNA presents an equilibrium of 1.7030 g/cm3 and a Tm of 88 degrees C. The guanine plus cytosine content in both DNAs has been calculated from tumour results and compared with the content in normal rat liver cells M-DNA of tumour cells presents a higher guanine plus cytosine content than N-DNA, whereas in normal liver cells is higher in N-DNA. N-DNAs of both normal and tumour cells have the same guanine plus cytosine content, whereas M-DNA from tumour cells presents a significant increase (about 35%) with regard to this from normal liver cells."}
{"id": "PMID:185672", "title": "The influence of prolonged ACTH treatment on rat adrenal steroidogenesis.", "content": "A series of in vitro experiments using pregnenolone-14C-4 and progesterone-14C-4 as precursors were performed to determine the effects of prolonged ACTH administration on adrenal steroid biogenesis in the rat. Under ACTH administration there was a tendency for the isolated steroids to have larger quantities and specific activities from both precursors than under control conditions. In contrast to the rabbit, the rat did not produce any detectable amounts of 17 alpha-hydroxylated steroids under either control or prolonged ACTH treatment using the very sensitive double isotope derivative assay for quantitation.", "contents": "The influence of prolonged ACTH treatment on rat adrenal steroidogenesis. A series of in vitro experiments using pregnenolone-14C-4 and progesterone-14C-4 as precursors were performed to determine the effects of prolonged ACTH administration on adrenal steroid biogenesis in the rat. Under ACTH administration there was a tendency for the isolated steroids to have larger quantities and specific activities from both precursors than under control conditions. In contrast to the rabbit, the rat did not produce any detectable amounts of 17 alpha-hydroxylated steroids under either control or prolonged ACTH treatment using the very sensitive double isotope derivative assay for quantitation."}
{"id": "PMID:185673", "title": "Systemic stress in the production of cardiac thrombosis in hypercholesterolaemic rats.", "content": "An experimental study to elucidate the effects of feeding a high fat diet, hypercholesterolaemia and superadded acute and chronic stress on the production of cardiac thrombosis was carried out in rats. The high fat diet contained 25 percent butter rat providing 45 percent calories from fat which produced significant increase of serum cholesterol and other lipids. Acute stress was induced by two injections of adrenaline on a single day which caused a marked transient alteration of haemodynamics. Chronic stress was of two types, physical and metabolic. The physical stress was induced by repeated exposure of the rats to electric shock or roller drum exercise, while metabolic stress was caused by repeated injection of ACTH. Rats of both acute and chronic stress groups showed variable degree of medial degeneration, hyaline and fibrinoid intimal deposits and calcification in coronary arteries. Cardiac thrombi were seen in 30 percent animals subjected to adrenaline shock. Among the chronic stress procedure 17 percent rats exposed to electric shock and only one rat of the ACTH group developed cardiac thrombosis but no thrombus was detected in those exposed to roller drum exercise. The myocardium showed patchy necrosis with or without calcification, Spontaneous mortality was maximum following acute adrenaline shock (25 %) while electric shock caused mortality in 17 percent animals. The other procedures did not lead to spontaneous mortality. This study highlights the significant role of high fat intake, hypercholesterolaemia and systemic stress in the pathogenesis of acute cardiac thrombosis and myocardial necrosis/infarction.", "contents": "Systemic stress in the production of cardiac thrombosis in hypercholesterolaemic rats. An experimental study to elucidate the effects of feeding a high fat diet, hypercholesterolaemia and superadded acute and chronic stress on the production of cardiac thrombosis was carried out in rats. The high fat diet contained 25 percent butter rat providing 45 percent calories from fat which produced significant increase of serum cholesterol and other lipids. Acute stress was induced by two injections of adrenaline on a single day which caused a marked transient alteration of haemodynamics. Chronic stress was of two types, physical and metabolic. The physical stress was induced by repeated exposure of the rats to electric shock or roller drum exercise, while metabolic stress was caused by repeated injection of ACTH. Rats of both acute and chronic stress groups showed variable degree of medial degeneration, hyaline and fibrinoid intimal deposits and calcification in coronary arteries. Cardiac thrombi were seen in 30 percent animals subjected to adrenaline shock. Among the chronic stress procedure 17 percent rats exposed to electric shock and only one rat of the ACTH group developed cardiac thrombosis but no thrombus was detected in those exposed to roller drum exercise. The myocardium showed patchy necrosis with or without calcification, Spontaneous mortality was maximum following acute adrenaline shock (25 %) while electric shock caused mortality in 17 percent animals. The other procedures did not lead to spontaneous mortality. This study highlights the significant role of high fat intake, hypercholesterolaemia and systemic stress in the pathogenesis of acute cardiac thrombosis and myocardial necrosis/infarction."}
{"id": "PMID:185674", "title": "Coenzyme alterations in rats with experimental hypertension.", "content": "The changes in the content of pyridine nucleotide coenzymes (NAD+ and NADH) in several models of experimentally induced hypertension, differing in mechanism (genetic spontaneous hypertension, renal one kidney Goldblatt hypertension, Adrenal-regeneration hypertension after INGLE-HIGGINS and Skelton, and NaC1 hypertension) were studied. An obvious difference between the changes in NAD+ and NADH in the various models of hypertension, was established: Thus in NaC1 hypertension a high level of the coenzymes in the kidneys and in the vessel wall was found, while the liver coenzyme content was in normal ranges. In ARH the coenzyme level was elevated not only in the kidneys and in the vessel wall, but in the liver as well. Treatment with hypotensive antilipolytic prostaglandin E1 decreased the coenzymes in ARH to normal values. Renal hypertension was characterized by a low content of oxidized NAD, an increased NADH, and a decreased NAD+/NADH ratio in the kidneys and the liver, while in the vessel wall the coenzyme level was moderately increased. The coenzyme changes in the kidneys of SHR were similar to those in renal hypertensive rats. However coenzyme level in the vessel wall of SHR was lower than in all the other forms of hypertension.", "contents": "Coenzyme alterations in rats with experimental hypertension. The changes in the content of pyridine nucleotide coenzymes (NAD+ and NADH) in several models of experimentally induced hypertension, differing in mechanism (genetic spontaneous hypertension, renal one kidney Goldblatt hypertension, Adrenal-regeneration hypertension after INGLE-HIGGINS and Skelton, and NaC1 hypertension) were studied. An obvious difference between the changes in NAD+ and NADH in the various models of hypertension, was established: Thus in NaC1 hypertension a high level of the coenzymes in the kidneys and in the vessel wall was found, while the liver coenzyme content was in normal ranges. In ARH the coenzyme level was elevated not only in the kidneys and in the vessel wall, but in the liver as well. Treatment with hypotensive antilipolytic prostaglandin E1 decreased the coenzymes in ARH to normal values. Renal hypertension was characterized by a low content of oxidized NAD, an increased NADH, and a decreased NAD+/NADH ratio in the kidneys and the liver, while in the vessel wall the coenzyme level was moderately increased. The coenzyme changes in the kidneys of SHR were similar to those in renal hypertensive rats. However coenzyme level in the vessel wall of SHR was lower than in all the other forms of hypertension."}
{"id": "PMID:185675", "title": "Alteration of plasma lipids and intermediates of lipid metabolism in healthy fasting volunteers by ethanol and fructose.", "content": "After healthy persons, aged between 20 and 35 years, had consumed either ethanol or ethanol and fructose, triglycerides, free glycerol, FFA, phospholipids and total cholesterol were determined. After a basic dosage of 0.5 g ethanol/kg body weight, each person received a maeintenance dosage of 0.1 g ethanol/kg body weight and hour. Control experiments were carried out on persons receiving only fructose and on fasting persons who consumed no ethanol. After 8 hrs, triglycerides rose in the ethanol group by 107 %, in the ethanol-fructose group by 63 %. FFA exhibited in both ethanol and ethanol-fructose groups an initial decrease, with a secondary increase in the ethanol group. The initial decrease was greater in the ethanol-fructose group. A significant rise in free glycerol by 419 % was observed 30 min after the intake of combined ethanol/fructose. Free glycerol rose under ethanol alone by 144%. The ohospholipids exhibited a slight rise in the ethanol group; no significant changes occured in the cholesterol. The blood ethanol level was lower under ethanol-fructose than under ethanol alone. The addition of fructose diminishes the ethanol-induced hypertriglyceridemia. Our investigations give further proof that, under short-term ethanol load, the fatty acids necessary for the increased triglyceride synthesis in the liver, originate predominantly from a peripheral lipolysis, and that changes in liver metabolism depending on the oxidation of ethanol are not of less importance for the development of the acute ethanol-induced hyperlipidemia.", "contents": "Alteration of plasma lipids and intermediates of lipid metabolism in healthy fasting volunteers by ethanol and fructose. After healthy persons, aged between 20 and 35 years, had consumed either ethanol or ethanol and fructose, triglycerides, free glycerol, FFA, phospholipids and total cholesterol were determined. After a basic dosage of 0.5 g ethanol/kg body weight, each person received a maeintenance dosage of 0.1 g ethanol/kg body weight and hour. Control experiments were carried out on persons receiving only fructose and on fasting persons who consumed no ethanol. After 8 hrs, triglycerides rose in the ethanol group by 107 %, in the ethanol-fructose group by 63 %. FFA exhibited in both ethanol and ethanol-fructose groups an initial decrease, with a secondary increase in the ethanol group. The initial decrease was greater in the ethanol-fructose group. A significant rise in free glycerol by 419 % was observed 30 min after the intake of combined ethanol/fructose. Free glycerol rose under ethanol alone by 144%. The ohospholipids exhibited a slight rise in the ethanol group; no significant changes occured in the cholesterol. The blood ethanol level was lower under ethanol-fructose than under ethanol alone. The addition of fructose diminishes the ethanol-induced hypertriglyceridemia. Our investigations give further proof that, under short-term ethanol load, the fatty acids necessary for the increased triglyceride synthesis in the liver, originate predominantly from a peripheral lipolysis, and that changes in liver metabolism depending on the oxidation of ethanol are not of less importance for the development of the acute ethanol-induced hyperlipidemia."}
{"id": "PMID:185676", "title": "Histochemical changes effected by aldosterone on compensatory renal growth in the rat.", "content": "The activity of succinic dehydrogenase, adenosine triphosphatase, alkaline phosphatase and cytochrome oxidase was studied histochemically in the remaining kidney of male albino rats which had been subjected to unilateral nephrectomy and were subsequently treated with aldosterone. A marked increase in the activity of succinic dehydrogenase, adenosine triphosphatase and alkaline phosphatase was noted on the initial postoperative days. The increase noted in succinic dehydrogenase activity is considered particularly important because in the control group succinic dehydrogenase activity remained unchanged throughout the experiment.", "contents": "Histochemical changes effected by aldosterone on compensatory renal growth in the rat. The activity of succinic dehydrogenase, adenosine triphosphatase, alkaline phosphatase and cytochrome oxidase was studied histochemically in the remaining kidney of male albino rats which had been subjected to unilateral nephrectomy and were subsequently treated with aldosterone. A marked increase in the activity of succinic dehydrogenase, adenosine triphosphatase and alkaline phosphatase was noted on the initial postoperative days. The increase noted in succinic dehydrogenase activity is considered particularly important because in the control group succinic dehydrogenase activity remained unchanged throughout the experiment."}
{"id": "PMID:185677", "title": "[Bursting pressure of colon in the rats and proteinase inhibition (author's transl)].", "content": "In the early postoperative period (third postoperative day) the colonic enterotomies show 45 per cent higher bursting pressure following administration of Aprotinin than the control group (p less than 0,02). On the fifth postoperative day no difference was noted between both groups. The interpretation of the results is difficult because specific parameters such as collagen content and collagenase activity were not determinated. The relationship between colonic anastomotic breakdown and collagenase and therefore the question of collagenase inhibition have to be discussed. It is suggested that activation of procollagenase is prevented because trypsin and kallikrein are inhibited by Aprotinin.", "contents": "[Bursting pressure of colon in the rats and proteinase inhibition (author's transl)]. In the early postoperative period (third postoperative day) the colonic enterotomies show 45 per cent higher bursting pressure following administration of Aprotinin than the control group (p less than 0,02). On the fifth postoperative day no difference was noted between both groups. The interpretation of the results is difficult because specific parameters such as collagen content and collagenase activity were not determinated. The relationship between colonic anastomotic breakdown and collagenase and therefore the question of collagenase inhibition have to be discussed. It is suggested that activation of procollagenase is prevented because trypsin and kallikrein are inhibited by Aprotinin."}
{"id": "PMID:185678", "title": "Pulmonary gas exchange in dogs ventilated with mixtures of oxygen with various inert gases.", "content": "To study the influence of physical properties of the respired gas on alveolar gas exchange, alveolar-arterial partial pressure differences for O2 and CO2 were measured in anesthetized dogs that were artificially ventilated with gas mixtures of O2 in N2, He, Ar or SF6. In both hyposia and normoxia alveolar-arterial PO2 differences had the tendency to increase slightly in the sequence of the respired inert gases SF6 less than Ar less than N2 less than He, while arterial-alveolar PCO2 differences remained practically unchanged. Pulmonary diffusing capacity for CO(DCO), determined by the single breath technique, revealed no significant differences between the four gas mixtures used. The possible mechanisms underlying these results are discussed in connection with the physical properties of the respired gas mixtures.", "contents": "Pulmonary gas exchange in dogs ventilated with mixtures of oxygen with various inert gases. To study the influence of physical properties of the respired gas on alveolar gas exchange, alveolar-arterial partial pressure differences for O2 and CO2 were measured in anesthetized dogs that were artificially ventilated with gas mixtures of O2 in N2, He, Ar or SF6. In both hyposia and normoxia alveolar-arterial PO2 differences had the tendency to increase slightly in the sequence of the respired inert gases SF6 less than Ar less than N2 less than He, while arterial-alveolar PCO2 differences remained practically unchanged. Pulmonary diffusing capacity for CO(DCO), determined by the single breath technique, revealed no significant differences between the four gas mixtures used. The possible mechanisms underlying these results are discussed in connection with the physical properties of the respired gas mixtures."}
{"id": "PMID:185683", "title": "Inhibition of elastase from granulocytes by the low molecular weight bronchial protease inhibitor.", "content": "The low molecular weight bronchial protease inhibitor isolated from purulent bronchial secretions of man was shown to be a potent inhibitor of the elastase from human granulocytes. At a molar ratio of 1:1, the inhibitor prevented elastase digestion of insoluble elastin and soluble elastin, and blocked the hydrolysis of t-BOC-L-alanine-p-nitrophenyl ester. The collagenolytic activity of granulocyte collagenase was not inhibited by the bronchial inhibitor. Antisera were raised in rabbits for the isolation of specific IgG fractions in order to localize and quantitate the inhibitor. 125I-labelled inhibitor was used to study enzyme interactions further by gel filtration. These studies demonstrated that the bronchial inhibitor formed firm complexes with granulocyte elastase but did not form complexes with granulocyte collagenase.", "contents": "Inhibition of elastase from granulocytes by the low molecular weight bronchial protease inhibitor. The low molecular weight bronchial protease inhibitor isolated from purulent bronchial secretions of man was shown to be a potent inhibitor of the elastase from human granulocytes. At a molar ratio of 1:1, the inhibitor prevented elastase digestion of insoluble elastin and soluble elastin, and blocked the hydrolysis of t-BOC-L-alanine-p-nitrophenyl ester. The collagenolytic activity of granulocyte collagenase was not inhibited by the bronchial inhibitor. Antisera were raised in rabbits for the isolation of specific IgG fractions in order to localize and quantitate the inhibitor. 125I-labelled inhibitor was used to study enzyme interactions further by gel filtration. These studies demonstrated that the bronchial inhibitor formed firm complexes with granulocyte elastase but did not form complexes with granulocyte collagenase."}
{"id": "PMID:185684", "title": "Influence of fat ingestion on lecithin:cholesterol acyl transfer rate in plasma of normal persons.", "content": "Lecithin:cholesterol acyl transfer (LCAT) rate in plasma and lipid concentrations in total plasma and high density lipoproteins (HDL) were determined before and after oral fat loads in healthy human subjects. The changes of LCAT rate after fat loading were compared to the effect of chylomicrons or lipid emulsions added in vitro to fasting plasma. After the fat loads there was an increase of mean molar LCAT rate simultaneous with an increase of mean phospholipid (PL) and HDL-PL concentration but not simultaneous with the increase of mean triglyceride (TG) concentration. Individual changes of molar LCAT rate correlated positively with changes of PL, HDL-PL, and unesterified cholesterol (UC) concentration but not with changes of TG concentration in the separate plasma samples after the fat loads. If only the maximal changes in each subject in any sample at any time after the loads were taken into account, the maximal increase of molar LCAT rate correlated positively with the maximal increase of TG concentration. Molar LCAT rate was not influenced by addition of chylomicrons in vitro but increased after addition of a PL emulsion. It is suggested that LCAT rate is stimulated by an excess of PL in plasma and substrate lipoproteins. This excess of PL may be created in vivo temporarily during chylomicron catabolism. The stimulation of LCAT rate by fat ingestion emphasizes the importance of LCAT as a connecting link between triglyceride and cholesterol metabolism.", "contents": "Influence of fat ingestion on lecithin:cholesterol acyl transfer rate in plasma of normal persons. Lecithin:cholesterol acyl transfer (LCAT) rate in plasma and lipid concentrations in total plasma and high density lipoproteins (HDL) were determined before and after oral fat loads in healthy human subjects. The changes of LCAT rate after fat loading were compared to the effect of chylomicrons or lipid emulsions added in vitro to fasting plasma. After the fat loads there was an increase of mean molar LCAT rate simultaneous with an increase of mean phospholipid (PL) and HDL-PL concentration but not simultaneous with the increase of mean triglyceride (TG) concentration. Individual changes of molar LCAT rate correlated positively with changes of PL, HDL-PL, and unesterified cholesterol (UC) concentration but not with changes of TG concentration in the separate plasma samples after the fat loads. If only the maximal changes in each subject in any sample at any time after the loads were taken into account, the maximal increase of molar LCAT rate correlated positively with the maximal increase of TG concentration. Molar LCAT rate was not influenced by addition of chylomicrons in vitro but increased after addition of a PL emulsion. It is suggested that LCAT rate is stimulated by an excess of PL in plasma and substrate lipoproteins. This excess of PL may be created in vivo temporarily during chylomicron catabolism. The stimulation of LCAT rate by fat ingestion emphasizes the importance of LCAT as a connecting link between triglyceride and cholesterol metabolism."}
{"id": "PMID:185685", "title": "Studies on human serum high-density lipoproteins. VI. Studies on a cholesterol ester-releasing reaction in vitro.", "content": "High-density lipoproteins (HDL) turn turbid during in vitro incubation, concomitant with the formation of a cholesterol ester-rich lipoprotein, designated HDL-sup. The increase in turbidity (A) formed in relation to incubation time (t) is an asymptotic function: A=Uo(1 - e-k1t), where Uo is the amount of HDL with the property of releasing HDL-sup and k1 the velocity constant of the reaction. The increase in turbidity and formation of HDL-sup was not related to cholesterol ester content of the incubated fraction nor to exogenous factors like bacterial growth. The in vitro incubation was accompanied by a cholesterol esterification with a mean production of 8 nmol cholesterol ester/mg HDL protein, but also by a more pronounced degradation of phosphatidyl choline, 148 nmol/mg HDL protein. These data indicate that the lipid changes are induced by a two-step lecithin:cholesterol acyltransfer (LCAT) reaction. This reaction caused in HDL lipids a consumption of surface material and an increase in 'lipid core', presumably leading to a weakening and disruption of the lipoprotein surface with a recombination of 'lipid core' material in the form of HDL-sup.", "contents": "Studies on human serum high-density lipoproteins. VI. Studies on a cholesterol ester-releasing reaction in vitro. High-density lipoproteins (HDL) turn turbid during in vitro incubation, concomitant with the formation of a cholesterol ester-rich lipoprotein, designated HDL-sup. The increase in turbidity (A) formed in relation to incubation time (t) is an asymptotic function: A=Uo(1 - e-k1t), where Uo is the amount of HDL with the property of releasing HDL-sup and k1 the velocity constant of the reaction. The increase in turbidity and formation of HDL-sup was not related to cholesterol ester content of the incubated fraction nor to exogenous factors like bacterial growth. The in vitro incubation was accompanied by a cholesterol esterification with a mean production of 8 nmol cholesterol ester/mg HDL protein, but also by a more pronounced degradation of phosphatidyl choline, 148 nmol/mg HDL protein. These data indicate that the lipid changes are induced by a two-step lecithin:cholesterol acyltransfer (LCAT) reaction. This reaction caused in HDL lipids a consumption of surface material and an increase in 'lipid core', presumably leading to a weakening and disruption of the lipoprotein surface with a recombination of 'lipid core' material in the form of HDL-sup."}
{"id": "PMID:185686", "title": "Relationship between lipid composition of very low density lipoprotein and electrophoretic mobility in agarose gel.", "content": "Eleven patients with type IV hyperlipoproteinaemia were investigated. The lipid composition of three very low density lipoprotein (VLDL) subfractions (Sf 100-400, 60-100, and 20-60) obtained by density gradient ultracentrifugation were compared with their electrophoretic mobility in agarose gel. With decreasing Sf values there was cholesterol and phospholipid enrichment relative to triglyceride. All subjects had lipoprotein with beta mobility (LPbeta) in the Sf fraction of 20-60. LPbeta may represent normally occurring intermediary particles.", "contents": "Relationship between lipid composition of very low density lipoprotein and electrophoretic mobility in agarose gel. Eleven patients with type IV hyperlipoproteinaemia were investigated. The lipid composition of three very low density lipoprotein (VLDL) subfractions (Sf 100-400, 60-100, and 20-60) obtained by density gradient ultracentrifugation were compared with their electrophoretic mobility in agarose gel. With decreasing Sf values there was cholesterol and phospholipid enrichment relative to triglyceride. All subjects had lipoprotein with beta mobility (LPbeta) in the Sf fraction of 20-60. LPbeta may represent normally occurring intermediary particles."}
{"id": "PMID:185687", "title": "Effects of ethyl alcohol on the adenosine 3', 5'-monophosphate system of the human gastric mucosa.", "content": "The effect of ethyl alcohol on the cyclic AMP system of the human gastric mucosa was studied in vitro. Corporic gastric mucosa was obtained from patients operated on for gastric or duodenal ulcers. Under the in vitro conditions used, ethanol at concentrations of 5% (v/v) or less stimulated the activity of adenylate cyclase and induced a dose-dependent rise of the gastric mucosal content of cyclic AMP. However, 10% ethanol increased the activity of adenylate cyclase but did not affect the gastric mucosal content of cyclic AMP. At the concentrations of 5 or 10%, ethanol inhibited the activity of cyclic AMP phosphodiesterase in a competitive manner. Reports in the literature indicate that oral ethanol stimulates the output of gastric acid at low but not at higher concentrations. The present results are consistent with the conception that the stimulatory effect of ethanol on the output of acid is mediated by an increase of the content of cyclic AMP in the gastric mucosa.", "contents": "Effects of ethyl alcohol on the adenosine 3', 5'-monophosphate system of the human gastric mucosa. The effect of ethyl alcohol on the cyclic AMP system of the human gastric mucosa was studied in vitro. Corporic gastric mucosa was obtained from patients operated on for gastric or duodenal ulcers. Under the in vitro conditions used, ethanol at concentrations of 5% (v/v) or less stimulated the activity of adenylate cyclase and induced a dose-dependent rise of the gastric mucosal content of cyclic AMP. However, 10% ethanol increased the activity of adenylate cyclase but did not affect the gastric mucosal content of cyclic AMP. At the concentrations of 5 or 10%, ethanol inhibited the activity of cyclic AMP phosphodiesterase in a competitive manner. Reports in the literature indicate that oral ethanol stimulates the output of gastric acid at low but not at higher concentrations. The present results are consistent with the conception that the stimulatory effect of ethanol on the output of acid is mediated by an increase of the content of cyclic AMP in the gastric mucosa."}
{"id": "PMID:185688", "title": "Unified mass-action theory for virus neutralization and radioimmunology.", "content": "All ideas implicit in the papers since 1953 involved in applying mass-action thermodynamics to antibody-antigen reactions are unified by the use of: (a) the intermediary concept of extent of reaction; (b) the concept of intrinsic association constant; (c) a statistical analysis for probable complexes; and (d) identification of the complex or complexes that contribute to the bioassay. Several general theoretical examples are given that show the limitations of linear interpretations of equilibrium data. Two practical examples from the literature illustrate foot-and-mouth disease virus and influenza virus neutralization.", "contents": "Unified mass-action theory for virus neutralization and radioimmunology. All ideas implicit in the papers since 1953 involved in applying mass-action thermodynamics to antibody-antigen reactions are unified by the use of: (a) the intermediary concept of extent of reaction; (b) the concept of intrinsic association constant; (c) a statistical analysis for probable complexes; and (d) identification of the complex or complexes that contribute to the bioassay. Several general theoretical examples are given that show the limitations of linear interpretations of equilibrium data. Two practical examples from the literature illustrate foot-and-mouth disease virus and influenza virus neutralization."}
{"id": "PMID:185689", "title": "[Neuropsychiatric findings in a case of paramyoclonus multiplex].", "content": "In a subject affected with multiple paramyoclonus, showing asyncronous, bilateral, intermittent, spontaneous myoclonic jerks, a neuro-psychiatric investigation was performed. Several day-time poligraphic recordings were normal, while the night-time ones showed the lack of myoclonic jerks throughout the sleep. Metrazol activation pointed out a probable hyperexcitability of brain stem reticular formation. The psychiatric investigation, performed with a psychodynamic approach let realize the existence of a distortion of neuro-psychological functions due to an impaired elaboration of emotional information and psycho-structuring engrams. The Authors conclude for a posible convergence of biological and psychological factors causing the clinical symptoms.", "contents": "[Neuropsychiatric findings in a case of paramyoclonus multiplex]. In a subject affected with multiple paramyoclonus, showing asyncronous, bilateral, intermittent, spontaneous myoclonic jerks, a neuro-psychiatric investigation was performed. Several day-time poligraphic recordings were normal, while the night-time ones showed the lack of myoclonic jerks throughout the sleep. Metrazol activation pointed out a probable hyperexcitability of brain stem reticular formation. The psychiatric investigation, performed with a psychodynamic approach let realize the existence of a distortion of neuro-psychological functions due to an impaired elaboration of emotional information and psycho-structuring engrams. The Authors conclude for a posible convergence of biological and psychological factors causing the clinical symptoms."}
{"id": "PMID:185690", "title": "[Sporadic recurrent hypertrophic polyneuropathy. Clinical-histological contributions on differential diagnosis].", "content": "The authors report about an own case of recurrent sporadic hypertrophic polyneuropathy and describe the clinical course and histologic picture with reference to the literature. The disease is characterized by recurrences of subacutely occurring polyradiculoneuropathy and sequent nearly complete remission. Clinical examination discloses preferentially symmetrically and distally occurring motor paresis while sensibility in most cases is less affected. The peripheral nerves may be enlarged after a few relapses and frequently painful to pressure during the bout. Excessive increase in CSF proteins is found only during the bout. Motor nerve conduction velocity is considerably reduced. Histological pictures typically present an onion bulb formation of the Schwann cells with marked proliferation of connective tissue. There frequently younger individuals are involved; the relation female to male is 3:1. Differentiation has to be made concerning hereditary and symptomatic forms of hypertrophic polyneuropathy. Etiological factors of the disease are discussed.", "contents": "[Sporadic recurrent hypertrophic polyneuropathy. Clinical-histological contributions on differential diagnosis]. The authors report about an own case of recurrent sporadic hypertrophic polyneuropathy and describe the clinical course and histologic picture with reference to the literature. The disease is characterized by recurrences of subacutely occurring polyradiculoneuropathy and sequent nearly complete remission. Clinical examination discloses preferentially symmetrically and distally occurring motor paresis while sensibility in most cases is less affected. The peripheral nerves may be enlarged after a few relapses and frequently painful to pressure during the bout. Excessive increase in CSF proteins is found only during the bout. Motor nerve conduction velocity is considerably reduced. Histological pictures typically present an onion bulb formation of the Schwann cells with marked proliferation of connective tissue. There frequently younger individuals are involved; the relation female to male is 3:1. Differentiation has to be made concerning hereditary and symptomatic forms of hypertrophic polyneuropathy. Etiological factors of the disease are discussed."}
{"id": "PMID:185691", "title": "Bronchiolar adenomatosis. A case report.", "content": "A case of bronchiolar adenomatosis (benign pulmonary adenomatosis) with unusually widespread pulmonary changes is presented. This disease is rare and occurs equally in both sexes. The tumourous growth is slow and can easily be mistaken for alveolar cell carcinoma, alveolar proteins, tuberculosis, sarcoidosis, or malignant pulmonary adenomatosis. The diagnosis can be made on a histological specimen from the affected lung. In spite of a benign histological picture, the disease may ultimately run an unfavourable course because of its malignant potentialities. A distinction between benign and malignant pulmonary adenomatosis may therefore only be made with certainty by a complete and careful postmortem examination.", "contents": "Bronchiolar adenomatosis. A case report. A case of bronchiolar adenomatosis (benign pulmonary adenomatosis) with unusually widespread pulmonary changes is presented. This disease is rare and occurs equally in both sexes. The tumourous growth is slow and can easily be mistaken for alveolar cell carcinoma, alveolar proteins, tuberculosis, sarcoidosis, or malignant pulmonary adenomatosis. The diagnosis can be made on a histological specimen from the affected lung. In spite of a benign histological picture, the disease may ultimately run an unfavourable course because of its malignant potentialities. A distinction between benign and malignant pulmonary adenomatosis may therefore only be made with certainty by a complete and careful postmortem examination."}
{"id": "PMID:185693", "title": "High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma.", "content": "The concentration of gamma-aminobutyric acid (GABA) and the activity of glutamate decarboxylase (GAD) in rat and human pancreas were measured by sensitive assay methods. The GABA concentration in rat pancreas was 2.51 millimoles per kilogram (dry weight) and GAD activity was 2.58 mmoles per kilogram per hour. The GABA concentration and GAD activity in rat Langerhans' islets were 18.9 mmole kg-1 and 66.7 mmole kg-1 hour-1, whereas those in the exocrine acini were 1.97 mmole kg-1 and 4.67 mmole kg-1 hour-1, respectively. In an insulinoma region of human pancreas the GABA concentration was 25.5 mmole kg-1 and the GAD activity was 138.2 mmole kg-1 hour-1, but in the surrounding nontumor region these values were only 2.81 mmole kg-1 and 2.01 mmole kg-1 hour-1, respectively, similar to the values in normal rat pancreas.", "contents": "High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma. The concentration of gamma-aminobutyric acid (GABA) and the activity of glutamate decarboxylase (GAD) in rat and human pancreas were measured by sensitive assay methods. The GABA concentration in rat pancreas was 2.51 millimoles per kilogram (dry weight) and GAD activity was 2.58 mmoles per kilogram per hour. The GABA concentration and GAD activity in rat Langerhans' islets were 18.9 mmole kg-1 and 66.7 mmole kg-1 hour-1, whereas those in the exocrine acini were 1.97 mmole kg-1 and 4.67 mmole kg-1 hour-1, respectively. In an insulinoma region of human pancreas the GABA concentration was 25.5 mmole kg-1 and the GAD activity was 138.2 mmole kg-1 hour-1, but in the surrounding nontumor region these values were only 2.81 mmole kg-1 and 2.01 mmole kg-1 hour-1, respectively, similar to the values in normal rat pancreas."}
{"id": "PMID:185694", "title": "Endorphins: profound behavioral effects in rats suggest new etiological factors in mental illness.", "content": "The endogenous morphinomimetic brain peptides Met5-enkephalin and alpha-, beta-, and gamma-endorphins have been evaluated in rats after intracerebrospinal fluid injection. beta-Endorphin produces marked, prolonged muscular rigidity and immobility similar to a catatonic state, counteracted by the opiate antagonist naloxone; this effect occurs at molar doses 1/100 to 1/400 that at which the other peptides or morphine block the response to painful stimuli. All peptides evoked dose-related, naloxone-reversible, wet-dog shakes in rats that had not been exposed to drugs. beta-Endorphin produced hypothermia, whereas gamma-endorphin produced hyperthermia. Such potent and divergent responses to naturally occurring subtances suggest that alterations in their homeostatic regulation could have etiological significance in mental illness.", "contents": "Endorphins: profound behavioral effects in rats suggest new etiological factors in mental illness. The endogenous morphinomimetic brain peptides Met5-enkephalin and alpha-, beta-, and gamma-endorphins have been evaluated in rats after intracerebrospinal fluid injection. beta-Endorphin produces marked, prolonged muscular rigidity and immobility similar to a catatonic state, counteracted by the opiate antagonist naloxone; this effect occurs at molar doses 1/100 to 1/400 that at which the other peptides or morphine block the response to painful stimuli. All peptides evoked dose-related, naloxone-reversible, wet-dog shakes in rats that had not been exposed to drugs. beta-Endorphin produced hypothermia, whereas gamma-endorphin produced hyperthermia. Such potent and divergent responses to naturally occurring subtances suggest that alterations in their homeostatic regulation could have etiological significance in mental illness."}
{"id": "PMID:185695", "title": "The C-fragment of beta-lipotropin: an endogenous neuroleptic or antipsychotogen?", "content": "Microinjection of the C-fragment (also called beta-endorphin), which is amino acid sequence 61-91 of the endogenous pituitary hormone, beta-lipotropin (beta-LPH), in the periaqueductal gray of the rat resulted in profound sedation and catalepsy, while microinjection of smaller fragments-that is, methionine-enkephalin [sequence beta-LPH-(61-65)] and its related pentapeptide, leucine enkephalin, and alpha-endorphin [sequence beta-LPH-(61-76)] resulted in attenuated forms of this behavior. This indicates that the C-fragment is an important neuromodulator of the central nervous system. The similarity of this behavior to that seen after systemic administration to experimental animals of exogenous neuroleptics suggests that a disturbance in the bioavailability of this neuropeptide to receptor sites in brain-perhaps due to lack of enzymatic cleavage from the circulating parent hormone, beta-lipotropin--may be an etiological factor in those psychopathological states for which the exogenous neuroleptics exert an ameliorative influence.", "contents": "The C-fragment of beta-lipotropin: an endogenous neuroleptic or antipsychotogen? Microinjection of the C-fragment (also called beta-endorphin), which is amino acid sequence 61-91 of the endogenous pituitary hormone, beta-lipotropin (beta-LPH), in the periaqueductal gray of the rat resulted in profound sedation and catalepsy, while microinjection of smaller fragments-that is, methionine-enkephalin [sequence beta-LPH-(61-65)] and its related pentapeptide, leucine enkephalin, and alpha-endorphin [sequence beta-LPH-(61-76)] resulted in attenuated forms of this behavior. This indicates that the C-fragment is an important neuromodulator of the central nervous system. The similarity of this behavior to that seen after systemic administration to experimental animals of exogenous neuroleptics suggests that a disturbance in the bioavailability of this neuropeptide to receptor sites in brain-perhaps due to lack of enzymatic cleavage from the circulating parent hormone, beta-lipotropin--may be an etiological factor in those psychopathological states for which the exogenous neuroleptics exert an ameliorative influence."}
{"id": "PMID:185692", "title": "The state of preservation of the cadaver of the Marquise of Tai found in the Han Tomb No. 1 in Mawangtui near Changsha as revealed by the fine structure of the muscle and other tissues.", "content": "The cadaver in the Han Tomb No. 1 at Mawangtui near Changsha, Human Province, excavated during the Great Proletarian Cultural Revolution and the movement to criticize Lin Piao and Confucius, is the remains of the wife of Litsang, the Marquis of Tai, the Chancellor of the principality of Changsha in the early Western Han Dynasty. The cadaver, buried underground for more than 2,100 years, is very well-preserved. The results presented in this paper are a part of the multidisciplinary investigations of the state of preservation of the cadaver, which, together with the studies of the pathological changes and the cause of death, and the attempts at unveiling the secret of preservation, constituted the main objectives of the coordinated research activities for the Han cadaver. This paper describes the fine structure of the muscle and other tissues of the cadaver. By an extensive analysis of the electron micrographs of the psoas muscle, by fractionation of various fragments of the same, and by simulation experiments with fresh human muscle incubated with cathepsins, it is possible to show that the muscle fibril assumes the shape of a bamboo shoot and is made up of a stack of alternate layers of two \"half A disks\" (one wing of the A cylinder minus the H zone) to one Z disk, held together by remnants of the microfilaments and wrapped up in the sarcoplasmic reticulum. The H zone of the A band and the I filaments have preferentially autolyzed. The best preserved portions of the Han muscle still retain antigenicity to a certain extent. The best-preserved of all proteins is collagen, retaining much of the macromolecular, chemical and biochemical characteristics, whereas pancreatic enzymes, cytochrome C and other stable proteins could no longer be detected. The separation of degradative processes into endogenous autolysis and exogenous putrefaction, the synthesis of the factor of macromolecular stability and the factor of autolytic environment, and the disentanglement of the changes occurring soon after death and the long-term gradual changes, have been discussed in an attempt to understand how the corpse changed in the course of time and why it was so well-preserved. The well-preservedness of the cadaver of the Marquise of Tai once again testifies to the creative wisdom of the labouring class of our ancestors.", "contents": "The state of preservation of the cadaver of the Marquise of Tai found in the Han Tomb No. 1 in Mawangtui near Changsha as revealed by the fine structure of the muscle and other tissues. The cadaver in the Han Tomb No. 1 at Mawangtui near Changsha, Human Province, excavated during the Great Proletarian Cultural Revolution and the movement to criticize Lin Piao and Confucius, is the remains of the wife of Litsang, the Marquis of Tai, the Chancellor of the principality of Changsha in the early Western Han Dynasty. The cadaver, buried underground for more than 2,100 years, is very well-preserved. The results presented in this paper are a part of the multidisciplinary investigations of the state of preservation of the cadaver, which, together with the studies of the pathological changes and the cause of death, and the attempts at unveiling the secret of preservation, constituted the main objectives of the coordinated research activities for the Han cadaver. This paper describes the fine structure of the muscle and other tissues of the cadaver. By an extensive analysis of the electron micrographs of the psoas muscle, by fractionation of various fragments of the same, and by simulation experiments with fresh human muscle incubated with cathepsins, it is possible to show that the muscle fibril assumes the shape of a bamboo shoot and is made up of a stack of alternate layers of two \"half A disks\" (one wing of the A cylinder minus the H zone) to one Z disk, held together by remnants of the microfilaments and wrapped up in the sarcoplasmic reticulum. The H zone of the A band and the I filaments have preferentially autolyzed. The best preserved portions of the Han muscle still retain antigenicity to a certain extent. The best-preserved of all proteins is collagen, retaining much of the macromolecular, chemical and biochemical characteristics, whereas pancreatic enzymes, cytochrome C and other stable proteins could no longer be detected. The separation of degradative processes into endogenous autolysis and exogenous putrefaction, the synthesis of the factor of macromolecular stability and the factor of autolytic environment, and the disentanglement of the changes occurring soon after death and the long-term gradual changes, have been discussed in an attempt to understand how the corpse changed in the course of time and why it was so well-preserved. The well-preservedness of the cadaver of the Marquise of Tai once again testifies to the creative wisdom of the labouring class of our ancestors."}
{"id": "PMID:185696", "title": "Histamine inhibition of neutrophil lysosomal enzyme release: an H2 histamine receptor response.", "content": "Human polymorphonuclear leukocytes treated with cytochalasin B release the lysosomal enzyme beta glucuronidase during contact with serum-activated zymosan particles. Histamine increases intracellular cyclic adenosine monophosphate and inhibits release of this enzyme. The H2 antihistamine metiamide blocks the histamine inhibition of lysosomal enzyme release and the increase in the intracellular adenoisine 3,5'-monophosphate of granulocytes. Chlorpheniramine, an H1 antihistamine, did not block the histamine inhibition of granulocyte lysosomal enzyme release.", "contents": "Histamine inhibition of neutrophil lysosomal enzyme release: an H2 histamine receptor response. Human polymorphonuclear leukocytes treated with cytochalasin B release the lysosomal enzyme beta glucuronidase during contact with serum-activated zymosan particles. Histamine increases intracellular cyclic adenosine monophosphate and inhibits release of this enzyme. The H2 antihistamine metiamide blocks the histamine inhibition of lysosomal enzyme release and the increase in the intracellular adenoisine 3,5'-monophosphate of granulocytes. Chlorpheniramine, an H1 antihistamine, did not block the histamine inhibition of granulocyte lysosomal enzyme release."}
{"id": "PMID:185697", "title": "Biosynthesis and function of gangliosides.", "content": "Gangliosides are unique acidic glycolipids that are selectively concentrated in the plasma membrane of cells. Surface labeling studies have demonstrated that at least a portion of the oligosaccharde chain of gangliosides extends beyond the hydrophe) is imbedded in the membrane bilayer. It is becoming increasingly apparent that gangliosides participate in the internalization of environmental signals elicited by cholera toxin and glycoprotein hormones such as thyrotropic hormone and chorionic gonadotropin as well as other substances such as interferon and possibly serotonin. The mechanism by which cholera toxin binds to a specific ganglioside receptor on the celraction of trophic agents with gangliosides. We would predict that analyogous phenomena involving gangliosides will be discovered in brain. The biosynthesis of gangliosides proceeds by the ordered sequential addition of sugars to the lipid moiety. These reactions are catalyzed by a cluster of membrane-bound glycosyltransferases. Any alteration in the activity or specificity of one of these enzymes will result in a dramatic change in the ganglioside pattern of an afflicted cell or organ. The drastic consequences that accompany abnormalities of ganglioside synthesis have been documented in a heritable metabolic disorder in vivo and in tumorigenic transformation of cells in vitro. In this article, we have attempted to unify these observations and to provide a reasonable interpretation of the role of gangliosides in mediating cell surface phenomena.", "contents": "Biosynthesis and function of gangliosides. Gangliosides are unique acidic glycolipids that are selectively concentrated in the plasma membrane of cells. Surface labeling studies have demonstrated that at least a portion of the oligosaccharde chain of gangliosides extends beyond the hydrophe) is imbedded in the membrane bilayer. It is becoming increasingly apparent that gangliosides participate in the internalization of environmental signals elicited by cholera toxin and glycoprotein hormones such as thyrotropic hormone and chorionic gonadotropin as well as other substances such as interferon and possibly serotonin. The mechanism by which cholera toxin binds to a specific ganglioside receptor on the celraction of trophic agents with gangliosides. We would predict that analyogous phenomena involving gangliosides will be discovered in brain. The biosynthesis of gangliosides proceeds by the ordered sequential addition of sugars to the lipid moiety. These reactions are catalyzed by a cluster of membrane-bound glycosyltransferases. Any alteration in the activity or specificity of one of these enzymes will result in a dramatic change in the ganglioside pattern of an afflicted cell or organ. The drastic consequences that accompany abnormalities of ganglioside synthesis have been documented in a heritable metabolic disorder in vivo and in tumorigenic transformation of cells in vitro. In this article, we have attempted to unify these observations and to provide a reasonable interpretation of the role of gangliosides in mediating cell surface phenomena."}
{"id": "PMID:185698", "title": "Electrotonic coupling: effective sign reversal by inhibitory neurons.", "content": "Neurons in the buccal ganglia of Navanax inermis which control circumferential muscles of the pharynx showed typical electrotonic coupling when there was little synaptic activity in them. When there was much inhibitory activity, the effective sign of coupling was reversed; that is, hyperpolarization and depolarization of one cell caused depolarization and hyperpolarization of the others. A neural circuit explaining these results involes inhibitory neurons electronically coupled to and also inhibitory to the circumferential neurons that are themselves coupled. This circuit offers considerable flexibility for mediation of different activity patterns in this simple neuronal system.", "contents": "Electrotonic coupling: effective sign reversal by inhibitory neurons. Neurons in the buccal ganglia of Navanax inermis which control circumferential muscles of the pharynx showed typical electrotonic coupling when there was little synaptic activity in them. When there was much inhibitory activity, the effective sign of coupling was reversed; that is, hyperpolarization and depolarization of one cell caused depolarization and hyperpolarization of the others. A neural circuit explaining these results involes inhibitory neurons electronically coupled to and also inhibitory to the circumferential neurons that are themselves coupled. This circuit offers considerable flexibility for mediation of different activity patterns in this simple neuronal system."}
{"id": "PMID:185699", "title": "[Lessons drawn from granulocyte transfusions in the treatment of infections complicating aplasia induced by anti-leukemic chemotherapy].", "content": "The authors report the results of leukocyte transfusions of white cells obtained by sedimentation from donors with chronic myeloid leukemia, and by a continuous output cell separator used in healthy donors. The percentage of therapeutic efficacy of these two techniques is respectively, 62 and 78%. Among the factors affecting transfusion efficacy, the dose of injected leukocytes, the immunological compatibility and the functional value of the injected cells, appear of major importance. A qualitative study of the polymorphs in chronic myeloid leukemia, assessed by reduction with tetrazolium nitro-blue (N.B.T.) after ingestion of latex particles, proved normal when studied in vivo in the recipient. The mode of action of transfused leukocytes is then discussed.", "contents": "[Lessons drawn from granulocyte transfusions in the treatment of infections complicating aplasia induced by anti-leukemic chemotherapy]. The authors report the results of leukocyte transfusions of white cells obtained by sedimentation from donors with chronic myeloid leukemia, and by a continuous output cell separator used in healthy donors. The percentage of therapeutic efficacy of these two techniques is respectively, 62 and 78%. Among the factors affecting transfusion efficacy, the dose of injected leukocytes, the immunological compatibility and the functional value of the injected cells, appear of major importance. A qualitative study of the polymorphs in chronic myeloid leukemia, assessed by reduction with tetrazolium nitro-blue (N.B.T.) after ingestion of latex particles, proved normal when studied in vivo in the recipient. The mode of action of transfused leukocytes is then discussed."}
{"id": "PMID:185700", "title": "[Episodes of fever in the agranulocytic phase of the treatment of acute myeloblastic leukemia in adults].", "content": "This retrospective study of 44 attacks of fever during the agranulocytic stage of treatment of acute myeloblastic leukemia in adults, sought the cause of the fever, the efficacy of antibiotic associations and the efficacy of white cell transfusions. In 28 cases, the fever was associated with bacterial or mycotic infection, proved in 19 cases. Appropriate antibiotic therapy alone was able to cure the fever, whereas white cell transfusion did not seem of any use. In the 16 other cases, the fever appeared alone. Antibiotic associations were ineffective, whereas the fever was cured by white cell transfusions or cure of the agranulocytosis.", "contents": "[Episodes of fever in the agranulocytic phase of the treatment of acute myeloblastic leukemia in adults]. This retrospective study of 44 attacks of fever during the agranulocytic stage of treatment of acute myeloblastic leukemia in adults, sought the cause of the fever, the efficacy of antibiotic associations and the efficacy of white cell transfusions. In 28 cases, the fever was associated with bacterial or mycotic infection, proved in 19 cases. Appropriate antibiotic therapy alone was able to cure the fever, whereas white cell transfusion did not seem of any use. In the 16 other cases, the fever appeared alone. Antibiotic associations were ineffective, whereas the fever was cured by white cell transfusions or cure of the agranulocytosis."}
{"id": "PMID:185701", "title": "[Anatomo-clinical and experimental studies on pneumocystis carinii. Preliminary note].", "content": "The authors have been interested over the last year in the detection of pneumocystis carinii in patients with immune deficiencies, whether natural or artificial. After a brief historical and general introduction, they discuss their procedures, the pathological substances available, the staining techniques and the examination of autopsy specimens. They undertook experimental work on this micro-organism, e.g. the development of the germ in immuno-depressed rats and, from this material, numerous varied trials of culture and inoculation in new-born animals, chick embryos and cell cultures. Microphotographs illustrate this work which is still in progress.", "contents": "[Anatomo-clinical and experimental studies on pneumocystis carinii. Preliminary note]. The authors have been interested over the last year in the detection of pneumocystis carinii in patients with immune deficiencies, whether natural or artificial. After a brief historical and general introduction, they discuss their procedures, the pathological substances available, the staining techniques and the examination of autopsy specimens. They undertook experimental work on this micro-organism, e.g. the development of the germ in immuno-depressed rats and, from this material, numerous varied trials of culture and inoculation in new-born animals, chick embryos and cell cultures. Microphotographs illustrate this work which is still in progress."}
{"id": "PMID:185704", "title": "[Bacterial infections and immunosuppression].", "content": "Organ transplantation and the modern treatment of leukemia have created a new situation favouring bacterial infection under immunosuppressive drugs. Exceptionally, due to pathogenic bacteria, these infections are usually due to various germs normally considered as inoffensive saprophytes, which may thus reveal immune deficiency in the patient. This immune failure, which is very pronounced in treated leukemic patients and following transplantation, is on the contrary often localised at a precise level during common infections. Knowledge of these levels is thus essential for the clinician who, in all infected patients, should assess the state of the skin, mucosal and tissue and humoral defences whether specific or non-specific in the light of modern immunological data. Infection in the immunodepressed subject requires urget treatment. Antibiotics are not the only form of treatment, one should supervise, maintain and restore adequate immune levels. Furthermore, antibiotics alone, although they reduce the frequency, do not finally improve the mortality rate from gram-negative septicemia acquired in hospital.", "contents": "[Bacterial infections and immunosuppression]. Organ transplantation and the modern treatment of leukemia have created a new situation favouring bacterial infection under immunosuppressive drugs. Exceptionally, due to pathogenic bacteria, these infections are usually due to various germs normally considered as inoffensive saprophytes, which may thus reveal immune deficiency in the patient. This immune failure, which is very pronounced in treated leukemic patients and following transplantation, is on the contrary often localised at a precise level during common infections. Knowledge of these levels is thus essential for the clinician who, in all infected patients, should assess the state of the skin, mucosal and tissue and humoral defences whether specific or non-specific in the light of modern immunological data. Infection in the immunodepressed subject requires urget treatment. Antibiotics are not the only form of treatment, one should supervise, maintain and restore adequate immune levels. Furthermore, antibiotics alone, although they reduce the frequency, do not finally improve the mortality rate from gram-negative septicemia acquired in hospital."}
{"id": "PMID:185705", "title": "[Infectious complications observed during the use of antimitotic agents in hematology].", "content": "During acute lymphoblastic leukemia in children, bacterial infections occur during initial treatment, whereas virus infections are observed during remission. Mycoses and pneumocystis carinii infections are the commonest late complications. During agranulocytosis, any prolonged fever should be considered as due to infection and probably septicemia. The bacteria are usually of digestive origin. Antibiotic therapy is only very inconstantly efficacious, and the course follows closely the number of granular cells, thus justifying the use of white cell transfusions.", "contents": "[Infectious complications observed during the use of antimitotic agents in hematology]. During acute lymphoblastic leukemia in children, bacterial infections occur during initial treatment, whereas virus infections are observed during remission. Mycoses and pneumocystis carinii infections are the commonest late complications. During agranulocytosis, any prolonged fever should be considered as due to infection and probably septicemia. The bacteria are usually of digestive origin. Antibiotic therapy is only very inconstantly efficacious, and the course follows closely the number of granular cells, thus justifying the use of white cell transfusions."}
{"id": "PMID:185706", "title": "[Diabetes mellitus in pheochromocytoma].", "content": "The frequency of latent disorders of glucose regulation during pheochromocytoma, is evaluated at 75% of cases. Detailed analysis of 83 cases with a diabetic state, gave the following results: insulin dependent diabetes, 37 cases. Non-insulin dependent, 14 cases. Latent diabetes, 32 cases. The characteristics of the insulin-dependent diabetes were not always suggestive. Insulin dependency was, however, unusual above a certain age. We noted loss of weight in spite of good control of the diabetes, the absence of acidosis and ketosis contrasting with rapid loss of weight. In fact, it is above all the hypertension which should lead to diagnosis. Surgical operation, cures or improves considerably the diabetic state, thus proving the symptomatic nature of this diabetes.", "contents": "[Diabetes mellitus in pheochromocytoma]. The frequency of latent disorders of glucose regulation during pheochromocytoma, is evaluated at 75% of cases. Detailed analysis of 83 cases with a diabetic state, gave the following results: insulin dependent diabetes, 37 cases. Non-insulin dependent, 14 cases. Latent diabetes, 32 cases. The characteristics of the insulin-dependent diabetes were not always suggestive. Insulin dependency was, however, unusual above a certain age. We noted loss of weight in spite of good control of the diabetes, the absence of acidosis and ketosis contrasting with rapid loss of weight. In fact, it is above all the hypertension which should lead to diagnosis. Surgical operation, cures or improves considerably the diabetic state, thus proving the symptomatic nature of this diabetes."}
{"id": "PMID:185707", "title": "[The nephrotoxicity of the methicillin-gentamycin combination. Apropos of 5 cases].", "content": "Interstitial nephritis with acute renal failure was observed in 5 cases out of 6 treated by the association of methicillin and gentamycin, wheras no case, was observed when each of these antibodies was used separately. The mechanisms which might explain the potentialisation of these two drugs are discussed.", "contents": "[The nephrotoxicity of the methicillin-gentamycin combination. Apropos of 5 cases]. Interstitial nephritis with acute renal failure was observed in 5 cases out of 6 treated by the association of methicillin and gentamycin, wheras no case, was observed when each of these antibodies was used separately. The mechanisms which might explain the potentialisation of these two drugs are discussed."}
{"id": "PMID:185708", "title": "[Immunoblasts. Morphology and significance in reactive and proliferative syndromes of lymphoid tissues].", "content": "The term immunoblast created by Dameshek, is useful in routine cytological and histopathological practice, for the diagnosis of lymphadenites and malignant blood diseases. This term designates a group of cells, the appearance of which is quite different from other cells of the lymphoid tissue. Their morphological characteristics are precise and they resemble transformed lymphocytes. These immunoblasts are derived from T and B lymphocytes. Using purely morphological methods the type B of certain immunoblasts may be suggested. Immunoblasts of the clear centers of follicles, immunoblasts undergoing plasma cell transformation, tumour cells constituting nodular immunoblastosarcomas, immunoblasts appearing in the tumor population of the myelomas and of Waldenstr\u00f6m's macroglobulinaemia. The term immunoblast which evokes precise morphological criteria, should be maintained. This term cannot designate only B lymphocytes, but also transformed lymphocytes of type B or T.", "contents": "[Immunoblasts. Morphology and significance in reactive and proliferative syndromes of lymphoid tissues]. The term immunoblast created by Dameshek, is useful in routine cytological and histopathological practice, for the diagnosis of lymphadenites and malignant blood diseases. This term designates a group of cells, the appearance of which is quite different from other cells of the lymphoid tissue. Their morphological characteristics are precise and they resemble transformed lymphocytes. These immunoblasts are derived from T and B lymphocytes. Using purely morphological methods the type B of certain immunoblasts may be suggested. Immunoblasts of the clear centers of follicles, immunoblasts undergoing plasma cell transformation, tumour cells constituting nodular immunoblastosarcomas, immunoblasts appearing in the tumor population of the myelomas and of Waldenstr\u00f6m's macroglobulinaemia. The term immunoblast which evokes precise morphological criteria, should be maintained. This term cannot designate only B lymphocytes, but also transformed lymphocytes of type B or T."}
{"id": "PMID:185709", "title": "[Senile common bile duct. Radiological study].", "content": "From this study carried out under sufficiently strict conditions to analyze normal common bile ducts of the third to the tenth decade, with radio-geometric measurement redusurement reducing errors as far as possible, it appears that: a) there is no difference in the frequency and the density of opacification of the bile duct in young or elderly subjects, b) that the radiological diameter of the normal bile duct becomes enlarged with time, according to the formula: (see article) which may be considered in routine clinical practice as a true increase in diameter of about 1 mm per decade. The limits of true diameter of the bile duct, in our experience, were +/- 3 mm at 30 years to +/- 7 mm after 80 years.", "contents": "[Senile common bile duct. Radiological study]. From this study carried out under sufficiently strict conditions to analyze normal common bile ducts of the third to the tenth decade, with radio-geometric measurement redusurement reducing errors as far as possible, it appears that: a) there is no difference in the frequency and the density of opacification of the bile duct in young or elderly subjects, b) that the radiological diameter of the normal bile duct becomes enlarged with time, according to the formula: (see article) which may be considered in routine clinical practice as a true increase in diameter of about 1 mm per decade. The limits of true diameter of the bile duct, in our experience, were +/- 3 mm at 30 years to +/- 7 mm after 80 years."}
{"id": "PMID:185715", "title": "[Benign tumors of the pleura].", "content": "The authors report a case of benign tumour of the pleura in a 74 year old woman. This is a pediculated tumour of the right base posteriorly above the diaphragm, the pleural nature of which was recognised before surgery and which, microscopically, proved to be a localized, benign mesothelioma of fibroblastic type. Benigh tumours of the pleura are rare but raise two interesting problems: that of their precise origin which is debated, and their prognosis; the possibility of relapse should be borne in mind.", "contents": "[Benign tumors of the pleura]. The authors report a case of benign tumour of the pleura in a 74 year old woman. This is a pediculated tumour of the right base posteriorly above the diaphragm, the pleural nature of which was recognised before surgery and which, microscopically, proved to be a localized, benign mesothelioma of fibroblastic type. Benigh tumours of the pleura are rare but raise two interesting problems: that of their precise origin which is debated, and their prognosis; the possibility of relapse should be borne in mind."}
{"id": "PMID:185716", "title": "[Pulmonary metastasis from Vater's ampullomas].", "content": "The authors report two cases of carcinoma of the ampulla of Vater with numerous pulmonary metastases. This carcinoma is a malignant tumour with a very poor short-term prognosis. This tumour develops at the expense of the ampulla of Vater and may give rise to numerous pulmonary metastases and  carcinomato,s lymphangitis. Authors are not unanimous concerning the course and prognosis of these tumours. In fact, one may note two tendencies, one optimistic, which seems to us erroneous, the other pessimistic, which we share.", "contents": "[Pulmonary metastasis from Vater's ampullomas]. The authors report two cases of carcinoma of the ampulla of Vater with numerous pulmonary metastases. This carcinoma is a malignant tumour with a very poor short-term prognosis. This tumour develops at the expense of the ampulla of Vater and may give rise to numerous pulmonary metastases and  carcinomato,s lymphangitis. Authors are not unanimous concerning the course and prognosis of these tumours. In fact, one may note two tendencies, one optimistic, which seems to us erroneous, the other pessimistic, which we share."}
{"id": "PMID:185717", "title": "[Validity of bronchial flow measurement by Wright's air flowmeter. Comparison with maximal expiratory volume in a second].", "content": "The validity of measurement of bronchial air flow, using Wright's air flow meter, was studied comparing the maximum air flow thus obtained with the maximum expiratory volume in one second, used as unit of reference. During a first stage, the reproducibility of the test was determined this was excellent, 3.26% for the maximal flow rate and 2.48% for the maximum volume expired in one second. During a second stage were drawn up correlations between the two tests which were very narrow: O.971 in healthy sbjects, 0.919 in sick patients. The Wright flow meter is a strong, reliable and inexpensive instrument and will thus be very useful in the daily assessment of bronchiolar constriction at the bed side, and in the routine detection of obstructive syndromes.", "contents": "[Validity of bronchial flow measurement by Wright's air flowmeter. Comparison with maximal expiratory volume in a second]. The validity of measurement of bronchial air flow, using Wright's air flow meter, was studied comparing the maximum air flow thus obtained with the maximum expiratory volume in one second, used as unit of reference. During a first stage, the reproducibility of the test was determined this was excellent, 3.26% for the maximal flow rate and 2.48% for the maximum volume expired in one second. During a second stage were drawn up correlations between the two tests which were very narrow: O.971 in healthy sbjects, 0.919 in sick patients. The Wright flow meter is a strong, reliable and inexpensive instrument and will thus be very useful in the daily assessment of bronchiolar constriction at the bed side, and in the routine detection of obstructive syndromes."}
{"id": "PMID:185718", "title": "[Idiopathic pulmonary hemosiderosis. Apropos of 1 case].", "content": "Idiopathic pulmonary hemosiderosis gives rise to anemia, due to repeated intra-alveolar hemorrhage, the reabsorption of which leads to hemosiderin deposits in the lung parenchyma. The authors report a case in a young woman aged 24 years whose illness started with anemia, then two months later, with hemoptysis and a broncho-pulmonary syndrome with a low grade fever. On the 6th month, there occurred a hazy infiltrate of both lung bases which was fleeting, mobile and recurrent. In the light of this triad of anemia, hemoptysis and infiltrates, the diagnosis of idiopathic pulmonary hemosiderosis was made and confirmed by three examinations:--Lung biopsy: siderophages were found in the sub-mucosa,--Radio-isotope examination, using Fe 59 which revealed iron deposits in the lung,--A surgical lung biopsy which showed a congestive area and a fibrous area. The congestive area was the site of recent hemorrhage, the alveolar limits were filled with siderophages. The fibrous area was the site of chronic repair of older hemorrhage. It was mutilating. The course was complicated by massive bleeding which led to acute recovering respiratory failure. The patient is at present stabilised by corticosteroids. Three hundred cases of idiopathic pulmonary hemosiderosis have been reported in the world literature. Although the main characteristic is intra-alveolar hemorrhage, its course has not yet been determined. It seems however, to be due to an immunologic process as shown by the relationship between this curious disease and Goodpasture's syndrome.", "contents": "[Idiopathic pulmonary hemosiderosis. Apropos of 1 case]. Idiopathic pulmonary hemosiderosis gives rise to anemia, due to repeated intra-alveolar hemorrhage, the reabsorption of which leads to hemosiderin deposits in the lung parenchyma. The authors report a case in a young woman aged 24 years whose illness started with anemia, then two months later, with hemoptysis and a broncho-pulmonary syndrome with a low grade fever. On the 6th month, there occurred a hazy infiltrate of both lung bases which was fleeting, mobile and recurrent. In the light of this triad of anemia, hemoptysis and infiltrates, the diagnosis of idiopathic pulmonary hemosiderosis was made and confirmed by three examinations:--Lung biopsy: siderophages were found in the sub-mucosa,--Radio-isotope examination, using Fe 59 which revealed iron deposits in the lung,--A surgical lung biopsy which showed a congestive area and a fibrous area. The congestive area was the site of recent hemorrhage, the alveolar limits were filled with siderophages. The fibrous area was the site of chronic repair of older hemorrhage. It was mutilating. The course was complicated by massive bleeding which led to acute recovering respiratory failure. The patient is at present stabilised by corticosteroids. Three hundred cases of idiopathic pulmonary hemosiderosis have been reported in the world literature. Although the main characteristic is intra-alveolar hemorrhage, its course has not yet been determined. It seems however, to be due to an immunologic process as shown by the relationship between this curious disease and Goodpasture's syndrome."}
{"id": "PMID:185720", "title": "[Paraneoplastic hypercalcemia in primary bronchial cancer].", "content": "Paraneoplastic hypercalcemia is frequently observed in squamous cell carcinoma of the bronchus. Clinically, apart from the general symptoms which are always very marked, neurological signs are the most common. This hypercalcemia, accompanied by hypophosphatemia, is of sudden onset and immediately very high. Metabolic alkalosis, with hypokalemia and hypochloremia, differentiates it from true hyperparathyroidism. Symptomatic treatment is only transiently effective. However, the obvious effect of mitramycin may be useful before surgical operation, which alone produces a lasting normalisation of serum calcium. Inappropriate secretion of a parathormone substance by the tumour may be demonstrated by radio-immunoassay, and this explains a large number of cases of hypercalcemia but this does not exclude other possible factors in the etiology. Finally, hypercalcemia originally attributed to bony lysis, may be explained in some cases by a paraneoplastic process.", "contents": "[Paraneoplastic hypercalcemia in primary bronchial cancer]. Paraneoplastic hypercalcemia is frequently observed in squamous cell carcinoma of the bronchus. Clinically, apart from the general symptoms which are always very marked, neurological signs are the most common. This hypercalcemia, accompanied by hypophosphatemia, is of sudden onset and immediately very high. Metabolic alkalosis, with hypokalemia and hypochloremia, differentiates it from true hyperparathyroidism. Symptomatic treatment is only transiently effective. However, the obvious effect of mitramycin may be useful before surgical operation, which alone produces a lasting normalisation of serum calcium. Inappropriate secretion of a parathormone substance by the tumour may be demonstrated by radio-immunoassay, and this explains a large number of cases of hypercalcemia but this does not exclude other possible factors in the etiology. Finally, hypercalcemia originally attributed to bony lysis, may be explained in some cases by a paraneoplastic process."}
{"id": "PMID:185721", "title": "Gallium-67 tumor scanning.", "content": "Since its introduction in 1969, 67Ga has become the most widely employed tumor-scanning agent in nuclear medicine. While 67Ga is far from being the ideal tumor-scanning agent, it remains the best available isotope for this purpose. Gallium-67-citrate has been found to be of value in the staging and reevaluation of lymphomas as well as in detecting the extent and recurrence of lung tumors, breast tumors, malignant melanomas, testicular tumors, brain tumors, and malignant lesions involving the liver. In order to obtain maximum diagnostic value from gallium scanning, several technical factors have to be taken into consideration as well as an understanding of the nature of \"false-positive\" scans.", "contents": "Gallium-67 tumor scanning. Since its introduction in 1969, 67Ga has become the most widely employed tumor-scanning agent in nuclear medicine. While 67Ga is far from being the ideal tumor-scanning agent, it remains the best available isotope for this purpose. Gallium-67-citrate has been found to be of value in the staging and reevaluation of lymphomas as well as in detecting the extent and recurrence of lung tumors, breast tumors, malignant melanomas, testicular tumors, brain tumors, and malignant lesions involving the liver. In order to obtain maximum diagnostic value from gallium scanning, several technical factors have to be taken into consideration as well as an understanding of the nature of \"false-positive\" scans."}
{"id": "PMID:185727", "title": "Hypoglycemia: the \"undisease\".", "content": "Patients with a wise variety of medical problems have been labeled as having \"hypoglycemia\" during the past several years. Hypoglycemia, however, indicates only a diminished content of blood or plasma glucose. In individual cases the existence of hypoglycemia needs to be ascertained by objective laboratory measurements. Once confirmed, it is necessary to determine which of the many conditions capable of inducing hypoglycemia is present. Therapy must be directed against a specific diagnosis. It is not sufficient to decide by history without laboratory confirmation that a patient has hypoglycemia and then prescribe dietary modification.", "contents": "Hypoglycemia: the \"undisease\". Patients with a wise variety of medical problems have been labeled as having \"hypoglycemia\" during the past several years. Hypoglycemia, however, indicates only a diminished content of blood or plasma glucose. In individual cases the existence of hypoglycemia needs to be ascertained by objective laboratory measurements. Once confirmed, it is necessary to determine which of the many conditions capable of inducing hypoglycemia is present. Therapy must be directed against a specific diagnosis. It is not sufficient to decide by history without laboratory confirmation that a patient has hypoglycemia and then prescribe dietary modification."}
{"id": "PMID:185728", "title": "Leiomyosarcoma of the broad ligament coincident with ductal carcinoma of the breast.", "content": "Presented is a case of an isolated leiomyosarcoma of the broad ligament in a woman who had a synchronous ductal carcinoma of the breast. Carcinoma of the breast, thyroid, or colon is the most common second primary neoplasm in women with pelvic malignancy.", "contents": "Leiomyosarcoma of the broad ligament coincident with ductal carcinoma of the breast. Presented is a case of an isolated leiomyosarcoma of the broad ligament in a woman who had a synchronous ductal carcinoma of the breast. Carcinoma of the breast, thyroid, or colon is the most common second primary neoplasm in women with pelvic malignancy."}
{"id": "PMID:185729", "title": "Spontaneous cytomegalovirus mononucleosis-like syndrome and aseptic meningitis.", "content": "The spontaneous development of a cytomegalovirus infection in a healthy adult is described. This illness manifested with fever, headache, malaise, an absolute lymphocytosis with atypical lymphocytes, and liver function abnormalities, but without tonsillitis, pharyngitis, lymphadenopathy, or splenomegaly. Aseptic meningitis also was present. The pathogenesis of cytomegalovirus mononucelosis and its relationship to other related syndromes are discussed.", "contents": "Spontaneous cytomegalovirus mononucleosis-like syndrome and aseptic meningitis. The spontaneous development of a cytomegalovirus infection in a healthy adult is described. This illness manifested with fever, headache, malaise, an absolute lymphocytosis with atypical lymphocytes, and liver function abnormalities, but without tonsillitis, pharyngitis, lymphadenopathy, or splenomegaly. Aseptic meningitis also was present. The pathogenesis of cytomegalovirus mononucelosis and its relationship to other related syndromes are discussed."}
{"id": "PMID:185730", "title": "Endocrine control of plasma protein and volume.", "content": "The loss of blood volume initiates a sequence of events that begin with detection of the volume loss by cardiovascular receptors and the transmission of the signals of that loss to the central nervous system. Central neural processing leads to the release of multiple hormones that act together to induce an increase in extracellular osmolality. In response to the increase in extracellular osmolality, fluid shifts from cells to the interstitium, increasing intersititial volume and pressure. The increase in interstitial pressure leads to increased capillary and lymphatic return of fluid and to increased lymphatic return of preformed albumon. These events combine to form the second definitive phase of the restitution of blood volume, which is crucial both for the support of critical cardiovascular function and for the inhibition of the initial neuroendocrine response. If left unabated, this response may lead to the detrimental features of the metabolic response to injury. The degree of hyperosmolality following volume loss in injury may serve as an index of severity of that injury. The presence of the mechanism outlined provides a further rationale arguing in favor of prompt and adequate fluid therapy of the injuried and volume-depleted patient.", "contents": "Endocrine control of plasma protein and volume. The loss of blood volume initiates a sequence of events that begin with detection of the volume loss by cardiovascular receptors and the transmission of the signals of that loss to the central nervous system. Central neural processing leads to the release of multiple hormones that act together to induce an increase in extracellular osmolality. In response to the increase in extracellular osmolality, fluid shifts from cells to the interstitium, increasing intersititial volume and pressure. The increase in interstitial pressure leads to increased capillary and lymphatic return of fluid and to increased lymphatic return of preformed albumon. These events combine to form the second definitive phase of the restitution of blood volume, which is crucial both for the support of critical cardiovascular function and for the inhibition of the initial neuroendocrine response. If left unabated, this response may lead to the detrimental features of the metabolic response to injury. The degree of hyperosmolality following volume loss in injury may serve as an index of severity of that injury. The presence of the mechanism outlined provides a further rationale arguing in favor of prompt and adequate fluid therapy of the injuried and volume-depleted patient."}
{"id": "PMID:185731", "title": "A new technique for hemipelvectomy.", "content": "A new technique for hemipelvectomy has been developed in which a large anterior well vascularized flap is used. The preservation of an anterior flap is essential if the posterior flap cannot be preserved because of tumor involvement. The vascularized anterior flap may be superior to the posterior flap because of less dermal necrosis. Use of the anterior flap may increase the ease of hemipelvectomy and reduce blood loss at operation.", "contents": "A new technique for hemipelvectomy. A new technique for hemipelvectomy has been developed in which a large anterior well vascularized flap is used. The preservation of an anterior flap is essential if the posterior flap cannot be preserved because of tumor involvement. The vascularized anterior flap may be superior to the posterior flap because of less dermal necrosis. Use of the anterior flap may increase the ease of hemipelvectomy and reduce blood loss at operation."}
{"id": "PMID:185732", "title": "Oculogenital transmission of type 2 herpes simplex virus in adults.", "content": "Type 2 (genital) herpes simplex virus (HSV-2) was isolated from three patients (two adults and an 11-year-old girl) with acute ocular infections. Two of these patients had acute blepharoconjunctivitis and one had acute keratoconjunctivitis. Genital herpes infections had preceded the eye infections in the two adults. This was not the case in the 11-year-old, but she had been in close contact with her sister who had apparently had the genital disease. The study strongly suggests transmission of HSV-2 from the genital site to the eye.", "contents": "Oculogenital transmission of type 2 herpes simplex virus in adults. Type 2 (genital) herpes simplex virus (HSV-2) was isolated from three patients (two adults and an 11-year-old girl) with acute ocular infections. Two of these patients had acute blepharoconjunctivitis and one had acute keratoconjunctivitis. Genital herpes infections had preceded the eye infections in the two adults. This was not the case in the 11-year-old, but she had been in close contact with her sister who had apparently had the genital disease. The study strongly suggests transmission of HSV-2 from the genital site to the eye."}
{"id": "PMID:185733", "title": "Observed relationship between herpetic lesions and antigenic type of Herpesvirus hominis.", "content": "Of 171 available strains of Herpesvirus hominis isolated in this laboratory during the period 1950 to 1975, 166 could be readily typed as HV-1 or HV-2 by indirect immunofluorescence, while 5 have so far been untypable. Of 72 typable isolates from genitalia and nearby skin, all were HV-2. Of 81 typable isolates from mouth, eye or skin above the waist, 68(84%) were HV-1 and 13(16%) were HV-2. Of isolates from the eye only, 46 of 54(87%) were HV-1, 7(13%) were HV-2, and 1 could not be typed. When sera were available for herpesvirus antibody titrations, the pattern of antibody response tended to match the type of isolate. Clinical findings of 5 of the individuals with ocular herpes caused by HV-2 have been reviewed. The HV-2 infections appeared to be severe, typical herpetic keratoconjunctivitis, sometimes with deep infiltrates and stromal involvement.", "contents": "Observed relationship between herpetic lesions and antigenic type of Herpesvirus hominis. Of 171 available strains of Herpesvirus hominis isolated in this laboratory during the period 1950 to 1975, 166 could be readily typed as HV-1 or HV-2 by indirect immunofluorescence, while 5 have so far been untypable. Of 72 typable isolates from genitalia and nearby skin, all were HV-2. Of 81 typable isolates from mouth, eye or skin above the waist, 68(84%) were HV-1 and 13(16%) were HV-2. Of isolates from the eye only, 46 of 54(87%) were HV-1, 7(13%) were HV-2, and 1 could not be typed. When sera were available for herpesvirus antibody titrations, the pattern of antibody response tended to match the type of isolate. Clinical findings of 5 of the individuals with ocular herpes caused by HV-2 have been reviewed. The HV-2 infections appeared to be severe, typical herpetic keratoconjunctivitis, sometimes with deep infiltrates and stromal involvement."}
{"id": "PMID:185735", "title": "Type 1 and type 2 herpes simplex virus in corneal cell cultures.", "content": "The pathogenicity of herpes simplex virus (HSV) in primary cultures of epithelia, stromal, and endothelial cells of rabbit corneas was studied at various incubation temperatures (30 degrees, 36 degrees, and 40 degrees C). We tested three strains each of type 1 (HSV-1) and type 2 (HSV-2). At all three temperatures, the epithelial cells appeared to be more susceptible to both HSV-1 and HSV-2 than the stromal and endothelial cells. In general, less HSV-1 was requered than HSV-2 to infect the same type of corneal cell at the same incubation temperature. At 40 degrees C, however, there was far less cell destruction by either HSV-1 or HSV-2 than at 30 degrees or 36 degrees C. This inhibition at 40 degrees C was more pronounced in the cells infected with HSV-2 than in those infected with HSV-1, and the inhibition was accompanied consistently by significant suppression of virus multiplication in the cells.", "contents": "Type 1 and type 2 herpes simplex virus in corneal cell cultures. The pathogenicity of herpes simplex virus (HSV) in primary cultures of epithelia, stromal, and endothelial cells of rabbit corneas was studied at various incubation temperatures (30 degrees, 36 degrees, and 40 degrees C). We tested three strains each of type 1 (HSV-1) and type 2 (HSV-2). At all three temperatures, the epithelial cells appeared to be more susceptible to both HSV-1 and HSV-2 than the stromal and endothelial cells. In general, less HSV-1 was requered than HSV-2 to infect the same type of corneal cell at the same incubation temperature. At 40 degrees C, however, there was far less cell destruction by either HSV-1 or HSV-2 than at 30 degrees or 36 degrees C. This inhibition at 40 degrees C was more pronounced in the cells infected with HSV-2 than in those infected with HSV-1, and the inhibition was accompanied consistently by significant suppression of virus multiplication in the cells."}
{"id": "PMID:185736", "title": "Recurrent herpes simplex uveitis in humans.", "content": "Herpetic uveitis in man is generally, although not always, a complication of chronic stromal disease of the cornea. It is characterized by pain, photophobia, and redness, and may be abrupt in onset, particularly in recurrent cases. It is often accompanied by a severe secondary glaucoma. Various theories of the pathogenesis are discussed. The weight of experimental evidence favors the proliferation of living virus in the uveal tissues as the cause of the inflammation, although the virus has been isolated only rarely from aspirated aqueous humor. Autoimmune factors must be considered. Cyclopegia is the most important element of treatment, most cases being self-limited and non-destructive. Secondary glaucoma sometimes poses a serious problem that must be treated by radical measures. Antiviral medications such as adenine arabinoside may play an important role in the treatment of resistant cases. Corticosteroid therapy is to be avoided, if possible.", "contents": "Recurrent herpes simplex uveitis in humans. Herpetic uveitis in man is generally, although not always, a complication of chronic stromal disease of the cornea. It is characterized by pain, photophobia, and redness, and may be abrupt in onset, particularly in recurrent cases. It is often accompanied by a severe secondary glaucoma. Various theories of the pathogenesis are discussed. The weight of experimental evidence favors the proliferation of living virus in the uveal tissues as the cause of the inflammation, although the virus has been isolated only rarely from aspirated aqueous humor. Autoimmune factors must be considered. Cyclopegia is the most important element of treatment, most cases being self-limited and non-destructive. Secondary glaucoma sometimes poses a serious problem that must be treated by radical measures. Antiviral medications such as adenine arabinoside may play an important role in the treatment of resistant cases. Corticosteroid therapy is to be avoided, if possible."}
{"id": "PMID:185734", "title": "The ocular manifestations of herpes zoster, varicella, infectious mononucleosis, and cytomegalovirus disease.", "content": "Herpes zoster, caused by varicella-zoster (V-Z) virus which also causes varicella (chickenpox), is usually a benign self-limited disease. However, when the ophthalmic division of the trigeminal nerve is affected, the ocular disease (ophthalmic zoster), although also usually mild and self-limited, may have severe complications (corneal scarring, glaucoma, iris atrophy, posterior synechiae, scleritis, motor disturbances, optic neuritis, retinitis, anterior segment necrosis, and phthisis bulbi and servere postherpetic neuralgia). Varicella affects the eye rarely (except for the typical lid lesions), but associated conjunctival and corneal lesions, iridocyclitis, glaucoma, chorioretinitis, and optic nerve lesions have been described. Infectious mononucleosis may involve the eye either by direct involvement or from a remote focus such as the central nervous system. Ocular manifestations of cytomegalovirus disease is usually limited to the choroid and retina unless involvement of the developing embryo occurs prior to the development of the eye.", "contents": "The ocular manifestations of herpes zoster, varicella, infectious mononucleosis, and cytomegalovirus disease. Herpes zoster, caused by varicella-zoster (V-Z) virus which also causes varicella (chickenpox), is usually a benign self-limited disease. However, when the ophthalmic division of the trigeminal nerve is affected, the ocular disease (ophthalmic zoster), although also usually mild and self-limited, may have severe complications (corneal scarring, glaucoma, iris atrophy, posterior synechiae, scleritis, motor disturbances, optic neuritis, retinitis, anterior segment necrosis, and phthisis bulbi and servere postherpetic neuralgia). Varicella affects the eye rarely (except for the typical lid lesions), but associated conjunctival and corneal lesions, iridocyclitis, glaucoma, chorioretinitis, and optic nerve lesions have been described. Infectious mononucleosis may involve the eye either by direct involvement or from a remote focus such as the central nervous system. Ocular manifestations of cytomegalovirus disease is usually limited to the choroid and retina unless involvement of the developing embryo occurs prior to the development of the eye."}
{"id": "PMID:185737", "title": "The biology of herpes simplex virus infection in humans.", "content": "Herpes simplex virus is a frequent cause of recurrent ocular, oral, genital or cutaneous eruptions in man. Lesions are highly localized and tend to recur at the same site. Among the most consistent factors provoking recurrence is root section of the trigeminal nerve. Clinical and experimental data suggest that herpes simplex virus is commonly resident within the trigeminal ganglia of man, where it may be responsible for recurrent oral or lip lesions, and is less frequently a resident of the second or third sacral ganglia where it might be responsible for genital eruptions. Generally, the trigeminal virus is type 1 and the sacral virus is type 2; the virus is only rarely recoverable from other sensory ganglia. Factors provoking the reactivation from the virus' latent site and the mechanism for reactivation remain largely unknown. Further study is needed to understand the behavior of HSV and other viruses in nervous system tissue.", "contents": "The biology of herpes simplex virus infection in humans. Herpes simplex virus is a frequent cause of recurrent ocular, oral, genital or cutaneous eruptions in man. Lesions are highly localized and tend to recur at the same site. Among the most consistent factors provoking recurrence is root section of the trigeminal nerve. Clinical and experimental data suggest that herpes simplex virus is commonly resident within the trigeminal ganglia of man, where it may be responsible for recurrent oral or lip lesions, and is less frequently a resident of the second or third sacral ganglia where it might be responsible for genital eruptions. Generally, the trigeminal virus is type 1 and the sacral virus is type 2; the virus is only rarely recoverable from other sensory ganglia. Factors provoking the reactivation from the virus' latent site and the mechanism for reactivation remain largely unknown. Further study is needed to understand the behavior of HSV and other viruses in nervous system tissue."}
{"id": "PMID:185738", "title": "Latent infections by herpes simplex virus in experimental animals.", "content": "Studies in experimental animals, initially the rabbit and more recently the mouse, have been a great importance in establishing present day concepts concerning the phenomenon of herpesvirus latency. These early observations coupled with more recent knowledge of virological consequences following surgical manipulation of the trigeminal tract have led to a general hypothesis for the natural history of herpetic infections: The infection follows a circuit from skin, mucous membrane, or eye (the primary infection) to the corresponding sensory ganglia via associated nerves. Virus becomes latent in the ganglia and later, as a result of one of the many provocations known to be associated with recurrence of herpetic lesions, is reactivated and travels via the nerve to the surface and again produces lesions. Current research investigating this hypothesis is reviewed.", "contents": "Latent infections by herpes simplex virus in experimental animals. Studies in experimental animals, initially the rabbit and more recently the mouse, have been a great importance in establishing present day concepts concerning the phenomenon of herpesvirus latency. These early observations coupled with more recent knowledge of virological consequences following surgical manipulation of the trigeminal tract have led to a general hypothesis for the natural history of herpetic infections: The infection follows a circuit from skin, mucous membrane, or eye (the primary infection) to the corresponding sensory ganglia via associated nerves. Virus becomes latent in the ganglia and later, as a result of one of the many provocations known to be associated with recurrence of herpetic lesions, is reactivated and travels via the nerve to the surface and again produces lesions. Current research investigating this hypothesis is reviewed."}
{"id": "PMID:185740", "title": "Experimental reactivation of ocular herpes simplex in rabbits.", "content": "Latent herpes simplex virus (HSV) is known to reside in the trigeminal ganglia. Our studies show that the temporary retrobulbar disruption of trigeminal nerve function in chronically infected animals caused a striking decrease in the number of positive HSV cultures obtained during the 20 weeks immediately following surgery. We found that the stereotaxic interruption of intracranial trigeminal nerve function prior to initial HSV infection dramatically reduced the incidence of peripheral recurrence of HSV. Stereotaxic stimulation of the trigeminal ganglion in chronically infected animals produced a significant increase in positive cultures within two days. But, direct neurosurgical stimulation of the trigeminal ganglion proved strikingly effective, producing 83% positive cultures at the eye within 48 hours of operation. These studies further substantiate the premise that the trigeminal ganglion serves as a reservoir for latent HSV from the trigeminal ganglion to its infectious form in the peripheral ocular tissues somehow involves the trigeminal nerve.", "contents": "Experimental reactivation of ocular herpes simplex in rabbits. Latent herpes simplex virus (HSV) is known to reside in the trigeminal ganglia. Our studies show that the temporary retrobulbar disruption of trigeminal nerve function in chronically infected animals caused a striking decrease in the number of positive HSV cultures obtained during the 20 weeks immediately following surgery. We found that the stereotaxic interruption of intracranial trigeminal nerve function prior to initial HSV infection dramatically reduced the incidence of peripheral recurrence of HSV. Stereotaxic stimulation of the trigeminal ganglion in chronically infected animals produced a significant increase in positive cultures within two days. But, direct neurosurgical stimulation of the trigeminal ganglion proved strikingly effective, producing 83% positive cultures at the eye within 48 hours of operation. These studies further substantiate the premise that the trigeminal ganglion serves as a reservoir for latent HSV from the trigeminal ganglion to its infectious form in the peripheral ocular tissues somehow involves the trigeminal nerve."}
{"id": "PMID:185739", "title": "Primary and secondary herpes simplex uveitis in rabbits.", "content": "Primary and secondary (recurrent) herpes simplex uveitis were studied in the rabbit eye. Intravitreal injection of live herpes simplex virus (HSV) produced primary uveitis, and reinjection of HSV intravitreally in an eye that had completely recovered from the primary disease produced secondary uveitis. The onset of primary herpes simplex uveitis was gradual, but the secondary disease developed immediately after the intravitreal reinjection. Only live HSV would produce primary uveitis, whereas both inactivated and live HSV could produce secondary uveitis. Infectious HSV could be isolated from the eye with primary uveitis, but not from the eye with secondary uveitis, a failure that appeared to be due in part to the persistence of anti-HSV neutralizing antibody in the eye after the primary uveitis. The results suggest that primary uveitis is caused by infection of the uveal tissue by live HSV, and that secondary uveitis is caused by HSV-induced immunological mechanisms.", "contents": "Primary and secondary herpes simplex uveitis in rabbits. Primary and secondary (recurrent) herpes simplex uveitis were studied in the rabbit eye. Intravitreal injection of live herpes simplex virus (HSV) produced primary uveitis, and reinjection of HSV intravitreally in an eye that had completely recovered from the primary disease produced secondary uveitis. The onset of primary herpes simplex uveitis was gradual, but the secondary disease developed immediately after the intravitreal reinjection. Only live HSV would produce primary uveitis, whereas both inactivated and live HSV could produce secondary uveitis. Infectious HSV could be isolated from the eye with primary uveitis, but not from the eye with secondary uveitis, a failure that appeared to be due in part to the persistence of anti-HSV neutralizing antibody in the eye after the primary uveitis. The results suggest that primary uveitis is caused by infection of the uveal tissue by live HSV, and that secondary uveitis is caused by HSV-induced immunological mechanisms."}
{"id": "PMID:185746", "title": "Morphometric comparison of the midgut epithelial cells in male and female Aedes aegypti L. (Insecta, Diptera).", "content": "Midgut epithelial cells of male and female Aedes aegypti, 3 days after emergence, were compared morphometrically. The results of the present investigation concerning the female, are in good agreement with those of a previous study (Hecker et al., 1974), demonstrating that morphometric investigation of midgut epithelia in A. aegypti can successfully be reproduced, and that the mosquito strain used did not show quantitative morphological changes due to laboratory rearing. In males, the cells of the anterior (A) and posterior part (P, 'stomach') of the midgut differ in their quantitative composition. Higher values are found for the microvilli and for the basal labyrinth in the A-part. On the other hand a higher volume density of the mitochondria is present in the P-part. No significant differences are found in the A-part between males and females. Significant differences, however, are present in the P-part. Distinctly more rer in the female stomach can be correlated with the synthesis of enzymes for blood digestion, which are absent in the male. In addition, the more complex functions of the female P-part are also reflected by higher values for other organelles and membrane systems (e.g. mitochondria, basal labyrinth).", "contents": "Morphometric comparison of the midgut epithelial cells in male and female Aedes aegypti L. (Insecta, Diptera). Midgut epithelial cells of male and female Aedes aegypti, 3 days after emergence, were compared morphometrically. The results of the present investigation concerning the female, are in good agreement with those of a previous study (Hecker et al., 1974), demonstrating that morphometric investigation of midgut epithelia in A. aegypti can successfully be reproduced, and that the mosquito strain used did not show quantitative morphological changes due to laboratory rearing. In males, the cells of the anterior (A) and posterior part (P, 'stomach') of the midgut differ in their quantitative composition. Higher values are found for the microvilli and for the basal labyrinth in the A-part. On the other hand a higher volume density of the mitochondria is present in the P-part. No significant differences are found in the A-part between males and females. Significant differences, however, are present in the P-part. Distinctly more rer in the female stomach can be correlated with the synthesis of enzymes for blood digestion, which are absent in the male. In addition, the more complex functions of the female P-part are also reflected by higher values for other organelles and membrane systems (e.g. mitochondria, basal labyrinth)."}
{"id": "PMID:185747", "title": "The fine structure of the digestive system of Daphnia pulex (Crustacea: Cladocera).", "content": "The alimentary canal of Daphnia pulex consists of a tube-shaped foregut, a midgut (mesenteron) with an anterior pair of small diverticula, and a short hindgut. The foregut and hindgut are structurally similar. Each is formed by a low cuboidal epithelium 5 mum tall and lined with a chitinous intima. The midgut wall consists of a simple epithelium resting on a thick beaded basal lamina which is surrounded by a spiraling muscularis. Anteriorly the midgut cells are columnar in shape being 30 mum in height each having a basal nucleus, anteriorly concentrated mitochondria and in apical border of long thin microvilli. Posteriorly the midgut cells become progressively shorter so that in the posteriormost region of the midgut the cells are 5 mum tall and cuboidal in shape. The microvilli concomitantly become shorter and thicker. All mesenteron cells contain the usual cytoplasmic organelles. The paired digestive diverticula are simple evaginations of the midgut. The wall of each consists of a simple epithelium of cuboidal cells 25 mum in height, each with a brushed border of long thin microvilli. Enzyme secretion appears to be holocrine in mode and not confined to any one region of the mesenteron though definitely polarized anteriorly. The thin gut muscularis encircles the entire length of the midgut and caeca. Thick and thin filaments appear to be in a 6:1 ratio.", "contents": "The fine structure of the digestive system of Daphnia pulex (Crustacea: Cladocera). The alimentary canal of Daphnia pulex consists of a tube-shaped foregut, a midgut (mesenteron) with an anterior pair of small diverticula, and a short hindgut. The foregut and hindgut are structurally similar. Each is formed by a low cuboidal epithelium 5 mum tall and lined with a chitinous intima. The midgut wall consists of a simple epithelium resting on a thick beaded basal lamina which is surrounded by a spiraling muscularis. Anteriorly the midgut cells are columnar in shape being 30 mum in height each having a basal nucleus, anteriorly concentrated mitochondria and in apical border of long thin microvilli. Posteriorly the midgut cells become progressively shorter so that in the posteriormost region of the midgut the cells are 5 mum tall and cuboidal in shape. The microvilli concomitantly become shorter and thicker. All mesenteron cells contain the usual cytoplasmic organelles. The paired digestive diverticula are simple evaginations of the midgut. The wall of each consists of a simple epithelium of cuboidal cells 25 mum in height, each with a brushed border of long thin microvilli. Enzyme secretion appears to be holocrine in mode and not confined to any one region of the mesenteron though definitely polarized anteriorly. The thin gut muscularis encircles the entire length of the midgut and caeca. Thick and thin filaments appear to be in a 6:1 ratio."}
{"id": "PMID:185748", "title": "Evolution of the glycogen content and of glucose-6-phosphatase activity in the liver of Salmo gairdneri during development.", "content": "The evolution of the liver's glycogenic content, cytochemical characterization of the glycogen and glucose-6-phosphatase activity enable us to define three successive phases up to stage 36, just before the first feed. The grade which was low up to stage 24 is then due to beta-particles of ovule origin. Then, up to stage 27, there is a storage phase: alpha-particles appear and accumulate while the enzymatic activity remains non-existent. From the stage 28 to 36 the grade is progressively increasing, the enzymatic activity appears and increases. When the phase ends the liver is able to ensure glycemic regulation and to deal with exogenous nutritional contributions.", "contents": "Evolution of the glycogen content and of glucose-6-phosphatase activity in the liver of Salmo gairdneri during development. The evolution of the liver's glycogenic content, cytochemical characterization of the glycogen and glucose-6-phosphatase activity enable us to define three successive phases up to stage 36, just before the first feed. The grade which was low up to stage 24 is then due to beta-particles of ovule origin. Then, up to stage 27, there is a storage phase: alpha-particles appear and accumulate while the enzymatic activity remains non-existent. From the stage 28 to 36 the grade is progressively increasing, the enzymatic activity appears and increases. When the phase ends the liver is able to ensure glycemic regulation and to deal with exogenous nutritional contributions."}
{"id": "PMID:185741", "title": "Immunology of herpesvirus infection: immunity to herpes simplex virus in eye infections.", "content": "A gereral, overall pattern of the temporal relationship and interaction between cell and antibody-mediated immune responses following herpes simplex virus infection of the rabbit cornea can be synthesized from our studies. Cell-mediated immunity (CMI) appears early following infection, at a time when mononuclear and lymphocytic cellular proliferation occur at the limbus. Interaction between specifically immune lymphocytes with virus antigens are detected by lymphocyte blastogenesis and migration inhabiting factor. During stromal keratitis, a second phase of CMI involves transient virus-specific cytotoxic lymphocytes, which destroy cells that display viral-induced antigens on their surface. Chemotatic factors generated by viral antigens alone or with antiviral antibody or by virus-sensitized lymphocytes play a role in attracting polymorphonuclear leukocytes to the cornea during stromal keratitis. Soluble mediators of CMI secreated by activated lymphocytes act both specifically and nonspecifically on virus-infected cells, allowing cell destruction and making intracellular virus available for neutralization by antiviral antibody. Cell-mediated immunity in the acute infection, diminishes with the appearance of significant antiviral antibody titers. The late phase of the corneal immune response results from a local antigen-antibody interaction and is characterized by cells predominantly of the plasmacytic type. The presence of complement-dependent cytotoxic antibodies capable of destroying virus-infected cells provide an additional factor in restriction of infection.", "contents": "Immunology of herpesvirus infection: immunity to herpes simplex virus in eye infections. A gereral, overall pattern of the temporal relationship and interaction between cell and antibody-mediated immune responses following herpes simplex virus infection of the rabbit cornea can be synthesized from our studies. Cell-mediated immunity (CMI) appears early following infection, at a time when mononuclear and lymphocytic cellular proliferation occur at the limbus. Interaction between specifically immune lymphocytes with virus antigens are detected by lymphocyte blastogenesis and migration inhabiting factor. During stromal keratitis, a second phase of CMI involves transient virus-specific cytotoxic lymphocytes, which destroy cells that display viral-induced antigens on their surface. Chemotatic factors generated by viral antigens alone or with antiviral antibody or by virus-sensitized lymphocytes play a role in attracting polymorphonuclear leukocytes to the cornea during stromal keratitis. Soluble mediators of CMI secreated by activated lymphocytes act both specifically and nonspecifically on virus-infected cells, allowing cell destruction and making intracellular virus available for neutralization by antiviral antibody. Cell-mediated immunity in the acute infection, diminishes with the appearance of significant antiviral antibody titers. The late phase of the corneal immune response results from a local antigen-antibody interaction and is characterized by cells predominantly of the plasmacytic type. The presence of complement-dependent cytotoxic antibodies capable of destroying virus-infected cells provide an additional factor in restriction of infection."}
{"id": "PMID:185749", "title": "Venous plasma cyclic AMP in acute cerebrovascular disease.", "content": "Antecubital venous blood was sampled from stroke patients in the presence of disodium ethylenediamine tetraacetate. Plasma was analyzed for cyclic AMP applying a competitive protein binding method without any special pretreatment. In mild hemispheric infarction as manifested by moderate hemiparesis and/or dysarthria, plasma cyclic AMP remained in the normal range (8-18 picomoles/ml). In most of the cases with moderate infarction, the cyclic AMP level was distinctly below the normal range several days after the onset of symptoms. However, cyclic AMP remained in the normal range in severe infarction with signs of brain edema, and in two cases with moderately severe symptoms. One of the two cases suffered from later development of brain edema, and the other revealed a large lesion in brain scintigrams. The sizes of the lesion revealed in brain scintigrams were smaller in the moderate cases and larger in the severe cases, except in one of the cases mentioned above. It appeared that with plasma cyclic AMP levels we could predict the extent of the lesion, and perhaps the subsequent development of impending brain edema in a few days after the onset of cerebral infarction. In moderate cases of cerebral hemorrhage, judged from the consciousness, cyclic AMP decreased to a subnormal level 2-4 days after the onset. In severe cases it remained in the normal range. Subarachnoid hemorrhage showed significantly elevated cyclic AMP levels in the early stage.", "contents": "Venous plasma cyclic AMP in acute cerebrovascular disease. Antecubital venous blood was sampled from stroke patients in the presence of disodium ethylenediamine tetraacetate. Plasma was analyzed for cyclic AMP applying a competitive protein binding method without any special pretreatment. In mild hemispheric infarction as manifested by moderate hemiparesis and/or dysarthria, plasma cyclic AMP remained in the normal range (8-18 picomoles/ml). In most of the cases with moderate infarction, the cyclic AMP level was distinctly below the normal range several days after the onset of symptoms. However, cyclic AMP remained in the normal range in severe infarction with signs of brain edema, and in two cases with moderately severe symptoms. One of the two cases suffered from later development of brain edema, and the other revealed a large lesion in brain scintigrams. The sizes of the lesion revealed in brain scintigrams were smaller in the moderate cases and larger in the severe cases, except in one of the cases mentioned above. It appeared that with plasma cyclic AMP levels we could predict the extent of the lesion, and perhaps the subsequent development of impending brain edema in a few days after the onset of cerebral infarction. In moderate cases of cerebral hemorrhage, judged from the consciousness, cyclic AMP decreased to a subnormal level 2-4 days after the onset. In severe cases it remained in the normal range. Subarachnoid hemorrhage showed significantly elevated cyclic AMP levels in the early stage."}
{"id": "PMID:185750", "title": "Effect of dibutyryl cyclic AMP on neuromuscular transmission in myasthenia gravis.", "content": "The effect of dibutyryl 3',5'-cyclic monophosphate (D-cAMP) on the neuromuscular transmission was studied in a patient with myasthenia gravis during anesthesia. D-cAMP caused a slight increase in single twitch tension, and an initial transient decrease in tension which resulted from the trains of 2 Hz stimuli disappeared after D-cAMP. The finding of the present study suggests that D-cAMP has an anti-fatigue effect in patients with myasthenia gravis.", "contents": "Effect of dibutyryl cyclic AMP on neuromuscular transmission in myasthenia gravis. The effect of dibutyryl 3',5'-cyclic monophosphate (D-cAMP) on the neuromuscular transmission was studied in a patient with myasthenia gravis during anesthesia. D-cAMP caused a slight increase in single twitch tension, and an initial transient decrease in tension which resulted from the trains of 2 Hz stimuli disappeared after D-cAMP. The finding of the present study suggests that D-cAMP has an anti-fatigue effect in patients with myasthenia gravis."}
{"id": "PMID:185764", "title": "[Cytophotometric determination of DNA concentration in the cells of experimental brain tumors. II. Primary tumors of rat cerebellum induced by 9, 10-dimethyl-1, 2-benzanthracene].", "content": "The Feulgen-DNA cytophotometry was applied for studies of 31 rat cerebellum tumors induced by 9, 10-dimetyl-1,2-bensantracene. Most of these gliomas (22) were astrocytomas of different grades of malignancy. The histological diagnosis of other tumors was: glioblastoma -- 4, oligoastrocytoma -- 2, oligodendroglioma -- 1, gliosarcoma 1. The majority cells of 26 tumors had diploid or paradiploid DNA quantity, 4 tumors (1 astrocytoma, 3 dedifferentiated astroyctomas) had triploid modal classes. The tetraploid modal class and a large number of polyploid cells were found only once for glioblastoma multiforme. A supposition was made that drastic changes of ploidy could arise for the second time during the process of tumor evolution. The authors failed to show any exact differences in the ploidy of gliomas in rats with athyreosis or hyperthyreosis, and in the ploidy of somatic cells in control animals.", "contents": "[Cytophotometric determination of DNA concentration in the cells of experimental brain tumors. II. Primary tumors of rat cerebellum induced by 9, 10-dimethyl-1, 2-benzanthracene]. The Feulgen-DNA cytophotometry was applied for studies of 31 rat cerebellum tumors induced by 9, 10-dimetyl-1,2-bensantracene. Most of these gliomas (22) were astrocytomas of different grades of malignancy. The histological diagnosis of other tumors was: glioblastoma -- 4, oligoastrocytoma -- 2, oligodendroglioma -- 1, gliosarcoma 1. The majority cells of 26 tumors had diploid or paradiploid DNA quantity, 4 tumors (1 astrocytoma, 3 dedifferentiated astroyctomas) had triploid modal classes. The tetraploid modal class and a large number of polyploid cells were found only once for glioblastoma multiforme. A supposition was made that drastic changes of ploidy could arise for the second time during the process of tumor evolution. The authors failed to show any exact differences in the ploidy of gliomas in rats with athyreosis or hyperthyreosis, and in the ploidy of somatic cells in control animals."}
{"id": "PMID:185763", "title": "[Ultrastructural changes in the livers of rats following multiple injections of corticotropin and sodium ribonucleinate].", "content": "The mechanism of the corticotropin (ACTH) action was studied. It was found that daily injections of ACTH-zinc-phosphate (5 un./100 g) to intact albino rats for 14 days result in a disturbance of the hepatocytes ultrastructure. When the hormone was injected in combination with sodium ribonucleate (5 mg/100 g), the deviations were less pronounced, injections of the hormones to adrenalectomized rats did not change the ultrastructure of hepatocytes.", "contents": "[Ultrastructural changes in the livers of rats following multiple injections of corticotropin and sodium ribonucleinate]. The mechanism of the corticotropin (ACTH) action was studied. It was found that daily injections of ACTH-zinc-phosphate (5 un./100 g) to intact albino rats for 14 days result in a disturbance of the hepatocytes ultrastructure. When the hormone was injected in combination with sodium ribonucleate (5 mg/100 g), the deviations were less pronounced, injections of the hormones to adrenalectomized rats did not change the ultrastructure of hepatocytes."}
{"id": "PMID:185765", "title": "[Hormonal and vitamin regulation of glucose-6-phosphatases activity in the liver].", "content": "Glucose-6-phosphatase (G-6-Phase) activity in the rat liver is established to correlate directly with the content of corticosteroids in blood: it lowers with hypocorticoidism (adrenalectomy) and rises with hypercorticoidism (stress). The highest G-6-Phase activity in the liver of the intact animals is observed in autumn, the lowest one in spring, i.e. in the periods when the adrenals function has minimal and maximal values, respectively. Thiamin (0.4 g/kg) is shown to cause a decrease in the G-6-Phase activity in the liver of the intact rats and adrenalectomized or hypophysectomized animals. An assumption is advanced that the found in the experiment a pronounced insulin-like effect of vitamin B with respect to the G-6-Phase activity is connected with an intensified synthesis of the corresponding hormone in the pancreas.", "contents": "[Hormonal and vitamin regulation of glucose-6-phosphatases activity in the liver]. Glucose-6-phosphatase (G-6-Phase) activity in the rat liver is established to correlate directly with the content of corticosteroids in blood: it lowers with hypocorticoidism (adrenalectomy) and rises with hypercorticoidism (stress). The highest G-6-Phase activity in the liver of the intact animals is observed in autumn, the lowest one in spring, i.e. in the periods when the adrenals function has minimal and maximal values, respectively. Thiamin (0.4 g/kg) is shown to cause a decrease in the G-6-Phase activity in the liver of the intact rats and adrenalectomized or hypophysectomized animals. An assumption is advanced that the found in the experiment a pronounced insulin-like effect of vitamin B with respect to the G-6-Phase activity is connected with an intensified synthesis of the corresponding hormone in the pancreas."}
{"id": "PMID:185766", "title": "[Stability of lysosomal membranes with different protocols of freezing--thawing].", "content": "The non-sedimentary activity of the liver hydrolases (acid RNase, DNase, phosphatase and cathepsins) of albino rats was studied at different freezing-thawing programmes (rapid and two-staged). It is found that the non-sedimentary activity of hydrolases increases in case of all freezing-thawing programmes. The lowest activity is observed at two-staged programmes, and after rapid freezing and rapid hawing of lysosomes.", "contents": "[Stability of lysosomal membranes with different protocols of freezing--thawing]. The non-sedimentary activity of the liver hydrolases (acid RNase, DNase, phosphatase and cathepsins) of albino rats was studied at different freezing-thawing programmes (rapid and two-staged). It is found that the non-sedimentary activity of hydrolases increases in case of all freezing-thawing programmes. The lowest activity is observed at two-staged programmes, and after rapid freezing and rapid hawing of lysosomes."}
{"id": "PMID:185767", "title": "[Adrenaline and cyclic AMP stimulation of ketopentose and sedoheptulose formation in rat liver homogenates].", "content": "Formation of sedoheptulose-7-phosphate and ketopentose phosphate was studied in vitro as affected by epinephrine and cAMP. No effect of epinephrine on the activity of transketolase was found with ribose-5-phosphate as a substrate of the nonoxidative reactions of the pentose phosphate ccyle. Epinephrine and cAMP enhance the formation of ketopentoses and sedoheptulose with glycogen as a main carbohydrate source, which is most pronounced in the experiments with cold preincubation. The phosphorylase system mediate influence of epinephrine and cAMP on the nonoxidative reactions products may be assumed.", "contents": "[Adrenaline and cyclic AMP stimulation of ketopentose and sedoheptulose formation in rat liver homogenates]. Formation of sedoheptulose-7-phosphate and ketopentose phosphate was studied in vitro as affected by epinephrine and cAMP. No effect of epinephrine on the activity of transketolase was found with ribose-5-phosphate as a substrate of the nonoxidative reactions of the pentose phosphate ccyle. Epinephrine and cAMP enhance the formation of ketopentoses and sedoheptulose with glycogen as a main carbohydrate source, which is most pronounced in the experiments with cold preincubation. The phosphorylase system mediate influence of epinephrine and cAMP on the nonoxidative reactions products may be assumed."}
{"id": "PMID:185769", "title": "[Effect of thiol-oxidizing agents on several enzymes in rat liver mitochondria].", "content": "The sulphydryl groups of nonprotein thiols and proteins of mitochondria, activity of enzymes, oxidative phosphorylation and swelling of these organellas were studied as affected by the thiol-oxidizing agents. Diamide and azoester are shown to oxidize SH-groups of mitochondria, inhibit isocytrate dehydrogenase and succinate: cytochrome oxidation and inhibits energy-dependent swelling of mitochondria. Under the effect of azoester the rate of oxygen consumption by mitochondria increases and there occurs their sharp swelling.", "contents": "[Effect of thiol-oxidizing agents on several enzymes in rat liver mitochondria]. The sulphydryl groups of nonprotein thiols and proteins of mitochondria, activity of enzymes, oxidative phosphorylation and swelling of these organellas were studied as affected by the thiol-oxidizing agents. Diamide and azoester are shown to oxidize SH-groups of mitochondria, inhibit isocytrate dehydrogenase and succinate: cytochrome oxidation and inhibits energy-dependent swelling of mitochondria. Under the effect of azoester the rate of oxygen consumption by mitochondria increases and there occurs their sharp swelling."}
{"id": "PMID:185768", "title": "[Concentration of cyclic adenosine-3',5'-monophosphate in the tissues and its excretion in the urine of rats during ontogenesis].", "content": "The intracellular content of cyclic adenosine 3',5'-monophosphate (cAMP) in the liver and epididymal fat as well as excretion of cAMP with urea were studied in rats at the age of 1, 3, 12 and 24 months. No statistically significant age changes were found in the intracellular content of cAMP in the tissues. A decreases in the intensity of cAMP excretion with urea in the 12-month rats as compared to the one-month ones is statistically significant.", "contents": "[Concentration of cyclic adenosine-3',5'-monophosphate in the tissues and its excretion in the urine of rats during ontogenesis]. The intracellular content of cyclic adenosine 3',5'-monophosphate (cAMP) in the liver and epididymal fat as well as excretion of cAMP with urea were studied in rats at the age of 1, 3, 12 and 24 months. No statistically significant age changes were found in the intracellular content of cAMP in the tissues. A decreases in the intensity of cAMP excretion with urea in the 12-month rats as compared to the one-month ones is statistically significant."}
{"id": "PMID:185777", "title": "Canine cutaneous histiocytoma: ultrastructural and cytochemical observations.", "content": "Five canine cutaneous histiocytomas were studied by electron microscopy and esterase cytochemistry. The tumor cells contained irregular nuclei, characteristic lysosomal granules, and perinuclear microfilaments. The cells showed activity with alpha-naphthyl acetate esterase stains. These characteristics are evidence that this tumor originates from the mononuclear phagocyte system.", "contents": "Canine cutaneous histiocytoma: ultrastructural and cytochemical observations. Five canine cutaneous histiocytomas were studied by electron microscopy and esterase cytochemistry. The tumor cells contained irregular nuclei, characteristic lysosomal granules, and perinuclear microfilaments. The cells showed activity with alpha-naphthyl acetate esterase stains. These characteristics are evidence that this tumor originates from the mononuclear phagocyte system."}
{"id": "PMID:185778", "title": "Studies on rotavirus infection and diarrhoea in young calves.", "content": "The occurrence of diarrhoea in calves was monitored during the first three weeks of life. Calves fed amounts of colostrum sufficient to produce serum Ig levels in excess of 30 mg per ml did not develop diarrhoea, whereas calves fed less colostrum did. Rotaviruses and mycoplasma-like particles were observed in the faeces of calves with and without diarrhoea. The epidemiology of rotavirus infection in calves is discussed.", "contents": "Studies on rotavirus infection and diarrhoea in young calves. The occurrence of diarrhoea in calves was monitored during the first three weeks of life. Calves fed amounts of colostrum sufficient to produce serum Ig levels in excess of 30 mg per ml did not develop diarrhoea, whereas calves fed less colostrum did. Rotaviruses and mycoplasma-like particles were observed in the faeces of calves with and without diarrhoea. The epidemiology of rotavirus infection in calves is discussed."}
{"id": "PMID:185784", "title": "Argyrophil cell carcinoma (apudoma) of the esophagus. A histopathologic entity.", "content": "In a series of 79 cases of primary esophageal carcinoma resected at The Center for Adult Diseases, Osaka, there were six tumors with specific histopathologic features valid for the diagnosis of argyrophil cell carcinoma. Of the 6 tumors, 3 were studied electron microscopically and assay for ACTH content was performed on 4 tumors. Clinically, the ages of the 6 patients ranged from 56 to 71 years; two were women and four men. Four of the 6 patients died with widespread tumor recurrences within 9 months of operation. Microscopically, the 6 tumors were composed largely or almost entirely of small, spindle-shaped cells resembling those of oat cell carcinoma of the lung, and were characterized by the arrangement of tumor cells in solid sheets or anastomosing cords, the presence of argyrophil tumor cells, and the deposits of amyloid. Electron microscopically, the three tumors contained neurosecretory-type granules. Using bioassay or radioimmunoassay ACTH activity in the tumor tissues was detected in 3 out of the 4 tumors determined. From the light and electron microscopic characteristics and the assay evidence, it seems reasonable to conclude that the 6 tumors are endocrine polypeptide producing tumors (apudomas) that arise from argyrophil cells normally found among the basal cells of the esophageal mucosa, and that they represent a distinct histopathologic entity clearly distinguishable from other types of esophageal carcinomas.", "contents": "Argyrophil cell carcinoma (apudoma) of the esophagus. A histopathologic entity. In a series of 79 cases of primary esophageal carcinoma resected at The Center for Adult Diseases, Osaka, there were six tumors with specific histopathologic features valid for the diagnosis of argyrophil cell carcinoma. Of the 6 tumors, 3 were studied electron microscopically and assay for ACTH content was performed on 4 tumors. Clinically, the ages of the 6 patients ranged from 56 to 71 years; two were women and four men. Four of the 6 patients died with widespread tumor recurrences within 9 months of operation. Microscopically, the 6 tumors were composed largely or almost entirely of small, spindle-shaped cells resembling those of oat cell carcinoma of the lung, and were characterized by the arrangement of tumor cells in solid sheets or anastomosing cords, the presence of argyrophil tumor cells, and the deposits of amyloid. Electron microscopically, the three tumors contained neurosecretory-type granules. Using bioassay or radioimmunoassay ACTH activity in the tumor tissues was detected in 3 out of the 4 tumors determined. From the light and electron microscopic characteristics and the assay evidence, it seems reasonable to conclude that the 6 tumors are endocrine polypeptide producing tumors (apudomas) that arise from argyrophil cells normally found among the basal cells of the esophageal mucosa, and that they represent a distinct histopathologic entity clearly distinguishable from other types of esophageal carcinomas."}
{"id": "PMID:185785", "title": "The appearance and degradation of specific hepatocellular cytoplasmic inclusion bodies in rat liver due to D-galactosamine. I. The relation between the amount of liver glycogen and the appearance of the atypical dense bodies in the liver cell.", "content": "One of the most sensitive and specific signs of the galactosamine effect upon the rat liver cell is the appearance of PAS-positive and diastase-resistant granules within the cytoplasm of hepatocytes. Light-microscopic, histochemical, biochemical, and electron-microscopic findings reveal that the appearance of these ADB (= atypical dense bodies) depends upon a working glycogen metabolism at the time of GalN treatment. The ADB are composed of particles resembling, due to shape and size, ribosomes and beta particles of glycogen. Most of them are surrounded by the rER, but they are never enclosed by a limiting membrane. Due to sequential changes they can be generally classified into three types; the early, the intermediate, and the late type. In seven experiments it can be shown, that the appearance of the ADB depends upon the time and dosage after GalN treatment. They occur even if an additional treatment with galactose or uridine prevents the liver from the features of a hepatitis, as also shown in the livers of newborn animals up to 3 weeks of age. The histochemical response against various glucosidases, hexosaminidases, pronase, and RNAse as well as against various fixatives indicates that ADB are composed of, at least, two different constituents, the former RNAse-sensitive and visible with routine light-microscopic staining procedures, the latter RNA-resistant, PAS-positive, and invisible after staining with H & E or toluidine blue. The latter is diastase-resistant, suggesting that this portion of ADB does not represent the usual glycoproteins but some abnormal metabolite of glycogen. The ADB can be detected with maximal accumulation in the cytoplasm of hepatocytes at that time when the glycogen content determined in the liver homogenate by biochemical methods is greatly reduced.", "contents": "The appearance and degradation of specific hepatocellular cytoplasmic inclusion bodies in rat liver due to D-galactosamine. I. The relation between the amount of liver glycogen and the appearance of the atypical dense bodies in the liver cell. One of the most sensitive and specific signs of the galactosamine effect upon the rat liver cell is the appearance of PAS-positive and diastase-resistant granules within the cytoplasm of hepatocytes. Light-microscopic, histochemical, biochemical, and electron-microscopic findings reveal that the appearance of these ADB (= atypical dense bodies) depends upon a working glycogen metabolism at the time of GalN treatment. The ADB are composed of particles resembling, due to shape and size, ribosomes and beta particles of glycogen. Most of them are surrounded by the rER, but they are never enclosed by a limiting membrane. Due to sequential changes they can be generally classified into three types; the early, the intermediate, and the late type. In seven experiments it can be shown, that the appearance of the ADB depends upon the time and dosage after GalN treatment. They occur even if an additional treatment with galactose or uridine prevents the liver from the features of a hepatitis, as also shown in the livers of newborn animals up to 3 weeks of age. The histochemical response against various glucosidases, hexosaminidases, pronase, and RNAse as well as against various fixatives indicates that ADB are composed of, at least, two different constituents, the former RNAse-sensitive and visible with routine light-microscopic staining procedures, the latter RNA-resistant, PAS-positive, and invisible after staining with H & E or toluidine blue. The latter is diastase-resistant, suggesting that this portion of ADB does not represent the usual glycoproteins but some abnormal metabolite of glycogen. The ADB can be detected with maximal accumulation in the cytoplasm of hepatocytes at that time when the glycogen content determined in the liver homogenate by biochemical methods is greatly reduced."}
{"id": "PMID:185806", "title": "[Effect of a reduced diet on hyperlipoproteinemia in metabolic-alimentary obesity].", "content": "The effect of calorifically reduced diet No 8e on the lipoproteinic composition of the blood serum in patients with metabolic-alimentary adiposity was studied. Most of the patients examined demonstrated hyperlipoproteinemia, basically of the IIb type, more seldom of the IIa and IV types. Following a course of the reduced diet the frequency of hyperlipoproteinemia of the II, III and IV types declines and the content of atherogenid lipoprotein fractions in the serum goes down. In young patients the effect of a reduced diet on the lipoprotein composition of the blood serum proved most effective.", "contents": "[Effect of a reduced diet on hyperlipoproteinemia in metabolic-alimentary obesity]. The effect of calorifically reduced diet No 8e on the lipoproteinic composition of the blood serum in patients with metabolic-alimentary adiposity was studied. Most of the patients examined demonstrated hyperlipoproteinemia, basically of the IIb type, more seldom of the IIa and IV types. Following a course of the reduced diet the frequency of hyperlipoproteinemia of the II, III and IV types declines and the content of atherogenid lipoprotein fractions in the serum goes down. In young patients the effect of a reduced diet on the lipoprotein composition of the blood serum proved most effective."}
{"id": "PMID:185809", "title": "[Mechanism of resistance of a clone isolated from L cells chronically infected with the virus of vesicular stomatitis].", "content": "The results of the study on antiviral immunity acquired by L cells to vesicular stomatitis virus are presented. We failed to detect the presence of the indicator virus in the resistant culture by means of virological, electron microscopic or cytochemical methods. Molecular hybrization experiments demonstrated the lack in the nuclear DNA of sequences homologous to vesicular stomatitis virus RNA.", "contents": "[Mechanism of resistance of a clone isolated from L cells chronically infected with the virus of vesicular stomatitis]. The results of the study on antiviral immunity acquired by L cells to vesicular stomatitis virus are presented. We failed to detect the presence of the indicator virus in the resistant culture by means of virological, electron microscopic or cytochemical methods. Molecular hybrization experiments demonstrated the lack in the nuclear DNA of sequences homologous to vesicular stomatitis virus RNA."}
{"id": "PMID:185813", "title": "[Aetiological studies on viral pneumonia (author's transl)].", "content": "401 cases of viral pneumonia diagnosed between January 1973 and August 1975 were investigated serologically by the complement-fixation test. The percentage distribution of the responsible pathogenic organism in this series of cases was as follows: influenza virus A 45.9%, Mycoplasma pneumoniae 19.5%, Coxsackie B viruses 9.2%, cytomegalovirus 7.5% and Chlamydia psittaci 8.5%. The remaining 9.4% cases were caused by adeno, parainfluenza, measles, influenza B, herpes simplex and respiratory syncytial viruses. Influenza virus was found mainly in elderly people (mean age 58.4 years), whilst pneumonia due to Mycoplasma occurred mainly in young adults (mean age 24.4 years). Infections with Coxsackie B viruses were almost entirely restriced to the warmer months; by contrast, the influenza virus was usually found in epidemic form and only during a few weeks in winter.", "contents": "[Aetiological studies on viral pneumonia (author's transl)]. 401 cases of viral pneumonia diagnosed between January 1973 and August 1975 were investigated serologically by the complement-fixation test. The percentage distribution of the responsible pathogenic organism in this series of cases was as follows: influenza virus A 45.9%, Mycoplasma pneumoniae 19.5%, Coxsackie B viruses 9.2%, cytomegalovirus 7.5% and Chlamydia psittaci 8.5%. The remaining 9.4% cases were caused by adeno, parainfluenza, measles, influenza B, herpes simplex and respiratory syncytial viruses. Influenza virus was found mainly in elderly people (mean age 58.4 years), whilst pneumonia due to Mycoplasma occurred mainly in young adults (mean age 24.4 years). Infections with Coxsackie B viruses were almost entirely restriced to the warmer months; by contrast, the influenza virus was usually found in epidemic form and only during a few weeks in winter."}
{"id": "PMID:185814", "title": "[Current concepts in the physiology of fat absorption (author's transl)].", "content": "Current concepts of intestinal fat absorption are reviewed and the aspects of intraluminal formation and the role of the mixed lipid micelle, the concept of the unstirred water layer and the role of the fatty acid-binding protein in the intracellular transport of long-chain fatty acids are particularly emphasized. In addition, several aspects of intestinal lipoprotein production, secretion and metabolism are discussed.", "contents": "[Current concepts in the physiology of fat absorption (author's transl)]. Current concepts of intestinal fat absorption are reviewed and the aspects of intraluminal formation and the role of the mixed lipid micelle, the concept of the unstirred water layer and the role of the fatty acid-binding protein in the intracellular transport of long-chain fatty acids are particularly emphasized. In addition, several aspects of intestinal lipoprotein production, secretion and metabolism are discussed."}
{"id": "PMID:185810", "title": "[Development of cellular immunity in patients with viral hepatitis].", "content": "The development of cell-mediated immunity (CMI) to the surface antigen of hepatitis B virus (HBSAg) and Botevgrad antigen (BA) was traced in 50 hepatitis patients. Migration inhibition test (MIT) was performed with purified HBSg and AB. Blood samples from every hepatitis patient were obtained at the beginning of the icteric phase, 10 days later and during convalescence. There was correlation between the two types of viral hepatitis and the type of cellular immune response. The development of CMI is associated with disappearance of HBSAg from the serum of hepatitis patients. CMI to HBSAg develops within 9-12 days after the onset of icterus and to BA during the first two days of icterus. There is a relationship between the persistence of HBSAg and CMI.", "contents": "[Development of cellular immunity in patients with viral hepatitis]. The development of cell-mediated immunity (CMI) to the surface antigen of hepatitis B virus (HBSAg) and Botevgrad antigen (BA) was traced in 50 hepatitis patients. Migration inhibition test (MIT) was performed with purified HBSg and AB. Blood samples from every hepatitis patient were obtained at the beginning of the icteric phase, 10 days later and during convalescence. There was correlation between the two types of viral hepatitis and the type of cellular immune response. The development of CMI is associated with disappearance of HBSAg from the serum of hepatitis patients. CMI to HBSAg develops within 9-12 days after the onset of icterus and to BA during the first two days of icterus. There is a relationship between the persistence of HBSAg and CMI."}
{"id": "PMID:185811", "title": "[Experimental study of the influence of reovirus infection on the course and outcome of pregnancy].", "content": "The possibility of intrauterine infection of fetuses of random-bred white mice with reovirus type 3 at various periods of pregnancy has been demonstrated. The unfavourable effect of reovirus infection on the course and outcome of pregnancy in some cases was manifested by impairment of embryogenesis, stillbirths and subsequent death of defective offsprings. Morphological examinations revealed marked pathological alterations in the lungs, brain, liver, and kidneys of suckling mice infected in utero.", "contents": "[Experimental study of the influence of reovirus infection on the course and outcome of pregnancy]. The possibility of intrauterine infection of fetuses of random-bred white mice with reovirus type 3 at various periods of pregnancy has been demonstrated. The unfavourable effect of reovirus infection on the course and outcome of pregnancy in some cases was manifested by impairment of embryogenesis, stillbirths and subsequent death of defective offsprings. Morphological examinations revealed marked pathological alterations in the lungs, brain, liver, and kidneys of suckling mice infected in utero."}
{"id": "PMID:185815", "title": "[Partial trisomy 9 with partial retention of the long arm (author's transl)].", "content": "A new case of partial trisomy 9 is reported. The characteristic clinical features consist of: 1. Microcephaly, enophthalmos, antimongloid slant of the eyes, hypertelorism, protruding ears, large nose, downward slant of the mouth corners, hypoplasia of phalanges. 2. Abnormal dermal ridge system and crease picture: irregularities of the ridge pattern of finger prints, palms and soles, a much reduced total ridge count (TRC), transverse palmar crease on both palms, underdevelopment of the C line. 3 Severe mental retardation. However, this case represents a variation of the chromosomal anomaly described so far, in as much as an important part of the long arm of the additional chromosome 9 is present.", "contents": "[Partial trisomy 9 with partial retention of the long arm (author's transl)]. A new case of partial trisomy 9 is reported. The characteristic clinical features consist of: 1. Microcephaly, enophthalmos, antimongloid slant of the eyes, hypertelorism, protruding ears, large nose, downward slant of the mouth corners, hypoplasia of phalanges. 2. Abnormal dermal ridge system and crease picture: irregularities of the ridge pattern of finger prints, palms and soles, a much reduced total ridge count (TRC), transverse palmar crease on both palms, underdevelopment of the C line. 3 Severe mental retardation. However, this case represents a variation of the chromosomal anomaly described so far, in as much as an important part of the long arm of the additional chromosome 9 is present."}
{"id": "PMID:185819", "title": "[The secretory function of the pancreas and the ageing progress (author's transl)].", "content": "A short literature survey is followed by an exposition of the methods of research (pancreozymin and secretin stimulation) and the results and their valuation. There is proved an decrease of the secretory pancreatic function.", "contents": "[The secretory function of the pancreas and the ageing progress (author's transl)]. A short literature survey is followed by an exposition of the methods of research (pancreozymin and secretin stimulation) and the results and their valuation. There is proved an decrease of the secretory pancreatic function."}
{"id": "PMID:185824", "title": "[Effect of gestagen therapy upon estradiol- and progesterone-receptor-level and 17beta-hydroxysteroid dehydrogenase in human endometrial adenocarcinoma (author's transl)].", "content": "Oestradiol was converted to oestrone about ten time more rapidly by subcellular fractions of normal human endometrium of the secretory phase than by tissue of the proliferative phase. In subcellular fractions of endometrial carcinoma the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity decreased with decreasing differentiation of the tumour. Most of the 17beta-HSD activity was located in mitochondrial and microsomal fractions of both normal and neoplastic endometrium. After treatment of patients with gestagens only the well differentiated carcinomata significantly increased in 17beta-HSD activity demonstrating that the hormonal stimulus leads to similar effects on the 17beta-HSD activity as in normal endometrium. Furthermore quantitative aspects of the in vitro binding of 3H-oestradiol and 3H-progesterone to receptor components from normal endometrium and endometrial carcinoma cytoplasmic fractions have been studied. In normal tissue the number of cytoplasmic binding sites for both oestradiol and progesterone varied dramatically during the menstrual cycle: number of oestradiol binding sites were highest during the proliferative phase and fell during the secretory phase; for progesterone site the contrary was the case. In all endometrial carcinomata high oestradiol binding activity was observed. In contrast the number of progesterone sites in the tumours was related to the state of differentiation, which paralled the progestional sensitivity of these tumours.", "contents": "[Effect of gestagen therapy upon estradiol- and progesterone-receptor-level and 17beta-hydroxysteroid dehydrogenase in human endometrial adenocarcinoma (author's transl)]. Oestradiol was converted to oestrone about ten time more rapidly by subcellular fractions of normal human endometrium of the secretory phase than by tissue of the proliferative phase. In subcellular fractions of endometrial carcinoma the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity decreased with decreasing differentiation of the tumour. Most of the 17beta-HSD activity was located in mitochondrial and microsomal fractions of both normal and neoplastic endometrium. After treatment of patients with gestagens only the well differentiated carcinomata significantly increased in 17beta-HSD activity demonstrating that the hormonal stimulus leads to similar effects on the 17beta-HSD activity as in normal endometrium. Furthermore quantitative aspects of the in vitro binding of 3H-oestradiol and 3H-progesterone to receptor components from normal endometrium and endometrial carcinoma cytoplasmic fractions have been studied. In normal tissue the number of cytoplasmic binding sites for both oestradiol and progesterone varied dramatically during the menstrual cycle: number of oestradiol binding sites were highest during the proliferative phase and fell during the secretory phase; for progesterone site the contrary was the case. In all endometrial carcinomata high oestradiol binding activity was observed. In contrast the number of progesterone sites in the tumours was related to the state of differentiation, which paralled the progestional sensitivity of these tumours."}
{"id": "PMID:185825", "title": "[Differing carcinogenic activity in BD-rats of 1-phenyl- and 1-(pyridyl-3)-3,3-diethyltriazene after single doses on 1., 10. or 30. day of life (author's transl)].", "content": "1-Phenyl- and 1-(pyridyl-3)-3,3-diethyltriazene have been investigated for carcinogenic effects in BD-rats after subcutaneous injection of a single dose of 50 mg of the compounds on day 1, 10, or 30 of life. The phenyl derivative showed a lower carcinogenic activity in comparison with the pyridyltriazene. Predominantly neurogenic tumors were observed. These were seen much more on treatment on day 1 or 10 of life than on treatment on day 30. The results confirm that the nervous system of rats is a target organ predominantly during early postnatal life.", "contents": "[Differing carcinogenic activity in BD-rats of 1-phenyl- and 1-(pyridyl-3)-3,3-diethyltriazene after single doses on 1., 10. or 30. day of life (author's transl)]. 1-Phenyl- and 1-(pyridyl-3)-3,3-diethyltriazene have been investigated for carcinogenic effects in BD-rats after subcutaneous injection of a single dose of 50 mg of the compounds on day 1, 10, or 30 of life. The phenyl derivative showed a lower carcinogenic activity in comparison with the pyridyltriazene. Predominantly neurogenic tumors were observed. These were seen much more on treatment on day 1 or 10 of life than on treatment on day 30. The results confirm that the nervous system of rats is a target organ predominantly during early postnatal life."}
{"id": "PMID:185826", "title": "Histochemical correlation between glycogen, nucleic acids and nucleases in pre-neoplastic and neoplastic lesions of rat liver after short-term administration of N-nitrosomorpholine.", "content": "After 7 weeks of oral administration of the carcinogen N-nitrosomorpholine (12 mg NNM ad 100 ml of drinking water) to male rats, marked hepatocellular changes were found predominantly in the centers of the lobules. These were loss of glycogen, disorganisation of the basophilic bodies and, sometimes, loss of cytoplasmic basophilia or pyroninophilia, necrotic cells and increase in the activity of acid DNAse and RNAse. These centrilobular alterations were reversible after withdrawal of the carcinogen. They are, therefore, attributed to the nonspecific-toxic effect of the carcinogen. In peripheral and midzonal regions of the lobules basically different cellular changes appeared which were unimportant during the phase of intoxication, but became prominent after cessation of the carcinogenic treatment. These lesions were: excessive storage of glycogen, displacement of basophilic bodies and an increase in cytoplasmic acidophilia. The hepatocytes showing these cytoplasmic changes initially formed foci. Neoplastic nodules and frank hepatocellular carcinomas developed later. During these later stages of the experiment both the foci and the nodules consisted of 4 main types of altered hepatocytes: 1) \"clear\" glycogen storage cells, 2) acidophilic cells, 3) vacuolated (fat storing) cells, 4) basophilic (pyroninophilic) cells poor in, or free from, glycogen. The larger nodules and carcinomas contained predominantly basophilic cells. The activity of nucleases, especially that of acid DNAse, decreased in small foci which as a rule developed later than the foci of glycogen storage. In most cells of neoplastic nodules and carcinomas the activity of these enzymes disappeared, but it reappeared in necrotic cells. The progressive alterations in the activity of the nucleases seemed to be related to the phenotypic expression of malignancy and could be a sign of a fundamental metabolic change taking place during a relatively late step in the malignant transformation.", "contents": "Histochemical correlation between glycogen, nucleic acids and nucleases in pre-neoplastic and neoplastic lesions of rat liver after short-term administration of N-nitrosomorpholine. After 7 weeks of oral administration of the carcinogen N-nitrosomorpholine (12 mg NNM ad 100 ml of drinking water) to male rats, marked hepatocellular changes were found predominantly in the centers of the lobules. These were loss of glycogen, disorganisation of the basophilic bodies and, sometimes, loss of cytoplasmic basophilia or pyroninophilia, necrotic cells and increase in the activity of acid DNAse and RNAse. These centrilobular alterations were reversible after withdrawal of the carcinogen. They are, therefore, attributed to the nonspecific-toxic effect of the carcinogen. In peripheral and midzonal regions of the lobules basically different cellular changes appeared which were unimportant during the phase of intoxication, but became prominent after cessation of the carcinogenic treatment. These lesions were: excessive storage of glycogen, displacement of basophilic bodies and an increase in cytoplasmic acidophilia. The hepatocytes showing these cytoplasmic changes initially formed foci. Neoplastic nodules and frank hepatocellular carcinomas developed later. During these later stages of the experiment both the foci and the nodules consisted of 4 main types of altered hepatocytes: 1) \"clear\" glycogen storage cells, 2) acidophilic cells, 3) vacuolated (fat storing) cells, 4) basophilic (pyroninophilic) cells poor in, or free from, glycogen. The larger nodules and carcinomas contained predominantly basophilic cells. The activity of nucleases, especially that of acid DNAse, decreased in small foci which as a rule developed later than the foci of glycogen storage. In most cells of neoplastic nodules and carcinomas the activity of these enzymes disappeared, but it reappeared in necrotic cells. The progressive alterations in the activity of the nucleases seemed to be related to the phenotypic expression of malignancy and could be a sign of a fundamental metabolic change taking place during a relatively late step in the malignant transformation."}
{"id": "PMID:185827", "title": "Lamellar structures in rat ova and their chemical composition.", "content": "The paper represents a study of the chemical composition of lamellar structures in rat ova during cleavage based on the morphology of their submicroscopic structure after the action of various fixatives and various methods of contrasting ultrathin sections and on the employment of cytochemical methods. Reactions to RNA, polysaccharides, acid and alkaline phosphatase, non-specific esterase, glucoso-6-phosphatase and succinate dehydrogenase were tested on a submicroscopic level; lipids were tested on a light-microscopic level. The results have shown that the lamellae are composed of proteins. No RNA, polysaccharides, lipids or any of the investigated enzymes were detected in lamellar structures. Lamellar structures, therefore, are considered to be storage material chiefly used in the second half of the cleavage for developmental processes in the rat ovum.", "contents": "Lamellar structures in rat ova and their chemical composition. The paper represents a study of the chemical composition of lamellar structures in rat ova during cleavage based on the morphology of their submicroscopic structure after the action of various fixatives and various methods of contrasting ultrathin sections and on the employment of cytochemical methods. Reactions to RNA, polysaccharides, acid and alkaline phosphatase, non-specific esterase, glucoso-6-phosphatase and succinate dehydrogenase were tested on a submicroscopic level; lipids were tested on a light-microscopic level. The results have shown that the lamellae are composed of proteins. No RNA, polysaccharides, lipids or any of the investigated enzymes were detected in lamellar structures. Lamellar structures, therefore, are considered to be storage material chiefly used in the second half of the cleavage for developmental processes in the rat ovum."}
{"id": "PMID:185833", "title": "Histochemical studies on the distribution of alkaline phosphatase, acid phosphatase, 5-nucleotidase and ATPase in various reproductive tissues of certain digenetic trematodes.", "content": "Out of other functions performed by vitellaria in digenetic trematodes, their role in the formation of shell globules and shell membrane of the capsule, as well as in the excretion of iron with the help of vitamin C is very important. The present histochemical work shows the localization of certain enzymes in different parts of the reproductive system of ten species of trematodes viz.: Neopronocephalus triangularis Mehra, 1932; Glossimetra orientalis Mehra, 1937; Orientodiscus lobatus Srivastava, 1938; Eumegacetes artemii Mehra, 1935; Ganeo tigrinus mehra et Negi, 1928; Encyclometra caudata Dollfus, 1928; Thapariella udaipurensis Gupta and Sharma, 1970; Paradistomoides indicum Narain et Das, 1929; Patagifer wesleyi Verma, 1936; Proalarioides tropidonotus Vidyarthi, 1937 and indicates their functional significance. The hydrolytic enzymes (alkaline phosphatase, acid phosphatase, 5-nucleotidase and ATPase) are suggestive of their involvement in the uptake of certain nutrients, glycogen and lipoprotein being very significant among others. The four enzymes could also be detected in testes, ovary, uterus, cirrus sac and egg shell. The possible functional significance of each enzyme has been discussed.", "contents": "Histochemical studies on the distribution of alkaline phosphatase, acid phosphatase, 5-nucleotidase and ATPase in various reproductive tissues of certain digenetic trematodes. Out of other functions performed by vitellaria in digenetic trematodes, their role in the formation of shell globules and shell membrane of the capsule, as well as in the excretion of iron with the help of vitamin C is very important. The present histochemical work shows the localization of certain enzymes in different parts of the reproductive system of ten species of trematodes viz.: Neopronocephalus triangularis Mehra, 1932; Glossimetra orientalis Mehra, 1937; Orientodiscus lobatus Srivastava, 1938; Eumegacetes artemii Mehra, 1935; Ganeo tigrinus mehra et Negi, 1928; Encyclometra caudata Dollfus, 1928; Thapariella udaipurensis Gupta and Sharma, 1970; Paradistomoides indicum Narain et Das, 1929; Patagifer wesleyi Verma, 1936; Proalarioides tropidonotus Vidyarthi, 1937 and indicates their functional significance. The hydrolytic enzymes (alkaline phosphatase, acid phosphatase, 5-nucleotidase and ATPase) are suggestive of their involvement in the uptake of certain nutrients, glycogen and lipoprotein being very significant among others. The four enzymes could also be detected in testes, ovary, uterus, cirrus sac and egg shell. The possible functional significance of each enzyme has been discussed."}
{"id": "PMID:185829", "title": "Conformation-controlled trans-effect of the proximal histidine in haemoglobins. An electron spin resonance study of monomeric nitrosyl-57Fe-haemoglobins.", "content": "A monomeric allosteric haemoglobin from Chironomus thummi thummi was reconstituted with 57Fe-haem. This reconstituted haemoglobin was found to be identical to the non-reconstituted material with regard to the O2-binding properties and the visible spectra. The 270 MHz proton magnetic resonance of the bis (cyano)-57Fe-haemin shows that the reconstituted haem is identical with the non-reconstituted haem. Furthermore it has been proved by proton magnetic resonance that in Chironomus haemoglobins the prosthetic group is proto-haem IX. The ESR spectrum of the native nitrosyl haemoglobin demonstrates rhombic symmetry of the haem iron (gxx=2.086, gyy=1.981, gzz=2.005) and hyperfine structures at gyy (aNepsilon=1.35 mT) and at gzz (a15NO=3.05 MT, a14NO=2.19 mT, aNepsilon=0.715 mT, a57Fe=0.38 mT). The spectrum is independent of pH and can be classified as a type II spectrum following the classification of ref. 2. NO-binding obviously stabilizes the tertiary structure of this haemoglobin in a \"tense\" conformation with a relatively strong sigma bond of the 5th ligand (Nepsilon of imidazole) and a relatively weak sigma bond of the 6th ligand (NO). Reaction of this haemoglobin with anionic, cationic and non-ionic detergents, respectively, leads to a transformation of the NO-ligated form into a \"relaxed\" conformation with a stretched or broken sigma bond of the 5th ligand (Nepsilon of imidazole) and a strong sigma bond of the 6th ligand (NO). The ESR spectrum of this modified NO-haemoglobin shows again a rhombic symmetry of the haem iron (gxx=2.10, gyy=2.06, gzz=2.010), but dramatically changes in the g tensors (low field shift), hyperfine structures and hyperfine splitting constants (a15NO=2.32 MT, a14NO=1.66 mT, a57Fe=0.48 mT). The hyperfine splitting is isotropic. Transition from the \"tense\" conformation to the \"relaxed\" conformation corresponds with an increase of the spin density at the iron atom by 26% and a decrease of the spin density at the NO ligand by 25%. The spin density at the Nepsilon of imidazole strongly decreases in the \"relaxed\" conformation, so that a hyperfine splitting of this ligand is not any more resolved. These results demonstrate the trans-effect of the proximal imidazole which in haemoglobins controls of the binding properties of the external ligand in trans-position.", "contents": "Conformation-controlled trans-effect of the proximal histidine in haemoglobins. An electron spin resonance study of monomeric nitrosyl-57Fe-haemoglobins. A monomeric allosteric haemoglobin from Chironomus thummi thummi was reconstituted with 57Fe-haem. This reconstituted haemoglobin was found to be identical to the non-reconstituted material with regard to the O2-binding properties and the visible spectra. The 270 MHz proton magnetic resonance of the bis (cyano)-57Fe-haemin shows that the reconstituted haem is identical with the non-reconstituted haem. Furthermore it has been proved by proton magnetic resonance that in Chironomus haemoglobins the prosthetic group is proto-haem IX. The ESR spectrum of the native nitrosyl haemoglobin demonstrates rhombic symmetry of the haem iron (gxx=2.086, gyy=1.981, gzz=2.005) and hyperfine structures at gyy (aNepsilon=1.35 mT) and at gzz (a15NO=3.05 MT, a14NO=2.19 mT, aNepsilon=0.715 mT, a57Fe=0.38 mT). The spectrum is independent of pH and can be classified as a type II spectrum following the classification of ref. 2. NO-binding obviously stabilizes the tertiary structure of this haemoglobin in a \"tense\" conformation with a relatively strong sigma bond of the 5th ligand (Nepsilon of imidazole) and a relatively weak sigma bond of the 6th ligand (NO). Reaction of this haemoglobin with anionic, cationic and non-ionic detergents, respectively, leads to a transformation of the NO-ligated form into a \"relaxed\" conformation with a stretched or broken sigma bond of the 5th ligand (Nepsilon of imidazole) and a strong sigma bond of the 6th ligand (NO). The ESR spectrum of this modified NO-haemoglobin shows again a rhombic symmetry of the haem iron (gxx=2.10, gyy=2.06, gzz=2.010), but dramatically changes in the g tensors (low field shift), hyperfine structures and hyperfine splitting constants (a15NO=2.32 MT, a14NO=1.66 mT, a57Fe=0.48 mT). The hyperfine splitting is isotropic. Transition from the \"tense\" conformation to the \"relaxed\" conformation corresponds with an increase of the spin density at the iron atom by 26% and a decrease of the spin density at the NO ligand by 25%. The spin density at the Nepsilon of imidazole strongly decreases in the \"relaxed\" conformation, so that a hyperfine splitting of this ligand is not any more resolved. These results demonstrate the trans-effect of the proximal imidazole which in haemoglobins controls of the binding properties of the external ligand in trans-position."}
{"id": "PMID:185830", "title": "Regulation of intracellular pyrophosphatase-activity and conservation of the phosphoanhydride-energy of inorganic pyrophosphate in microbial metabolism.", "content": "The conservation of the phosphoanhydride-energy of inorganic pyrophosphate (PP) in microbial metabolism requires a stringent metabolic control of the intracellular pyrophosphatases (PPases, EC 3.6.1.1). In this article, the rate of intracellular PP-liberation during biosynthesis of cellular constituents is calculated from the specific growth rate and the macromolecular composition of the respective microorganism. This rate is compared with the maximal specific activity of PPase in cell free extracts or purified enzyme preparations in order to investigate the possibility of the limitation of biosynthesis through PPase-activity. The catalytic and regulatory properties of microbial PPases are discussed in respect to the occurrence of PP-dependent ransphosphorylases. The evidence showing that certain anaerobic microorganisms including photosynthetic bacteria, can use PP instead of ATP as phosphate donor for transphosphorylation reactions will be discussed.", "contents": "Regulation of intracellular pyrophosphatase-activity and conservation of the phosphoanhydride-energy of inorganic pyrophosphate in microbial metabolism. The conservation of the phosphoanhydride-energy of inorganic pyrophosphate (PP) in microbial metabolism requires a stringent metabolic control of the intracellular pyrophosphatases (PPases, EC 3.6.1.1). In this article, the rate of intracellular PP-liberation during biosynthesis of cellular constituents is calculated from the specific growth rate and the macromolecular composition of the respective microorganism. This rate is compared with the maximal specific activity of PPase in cell free extracts or purified enzyme preparations in order to investigate the possibility of the limitation of biosynthesis through PPase-activity. The catalytic and regulatory properties of microbial PPases are discussed in respect to the occurrence of PP-dependent ransphosphorylases. The evidence showing that certain anaerobic microorganisms including photosynthetic bacteria, can use PP instead of ATP as phosphate donor for transphosphorylation reactions will be discussed."}
{"id": "PMID:185831", "title": "Photosynthetic electron carriers at a heptane-water interface.", "content": "Surface properties of monomolecular films of chlorophyll (Chl), plastocyanin (Pc), cytochrome c (Cyt) and ferridoxin (Fd) were measured at a heptane-water interface. Mixed films of Chl and the other components were examined in darkness and in light. The area/molecule, A, for Fd (from Cl. pasteurianum) is much larger at a heptane-water than Fd (from spinach) at an air-water interface. This difference in A may be the source of the Fd or the extent of denaturation at the different interfaces. There appears to be a photoreaction between Chl and Fd in the presence of ascorbate. The A for Cyt is much larger at a heptane-water than at an air-water interface. In mixed films there is a strong interaction between Chl and reduced Cyt in the dark. No such interaction is observed between Chl and oxidized Cyt. With mixed films of Chl and reduced Pc there is a significant, reversible, light induced change in deltaV.", "contents": "Photosynthetic electron carriers at a heptane-water interface. Surface properties of monomolecular films of chlorophyll (Chl), plastocyanin (Pc), cytochrome c (Cyt) and ferridoxin (Fd) were measured at a heptane-water interface. Mixed films of Chl and the other components were examined in darkness and in light. The area/molecule, A, for Fd (from Cl. pasteurianum) is much larger at a heptane-water than Fd (from spinach) at an air-water interface. This difference in A may be the source of the Fd or the extent of denaturation at the different interfaces. There appears to be a photoreaction between Chl and Fd in the presence of ascorbate. The A for Cyt is much larger at a heptane-water than at an air-water interface. In mixed films there is a strong interaction between Chl and reduced Cyt in the dark. No such interaction is observed between Chl and oxidized Cyt. With mixed films of Chl and reduced Pc there is a significant, reversible, light induced change in deltaV."}
{"id": "PMID:185832", "title": "Chirality of the hydrogen transfer to NAD catalyzed by myo-inositol dehydrogenase from Klebsiella pneumoniae.", "content": "Chirality, Hydrogen Transfer, myo-Inositol Dehydrogenase. The chirality of the hydrogen transfer to NAD catalyzed by myo-inositol dehydrogenase (myo-Inositol: NAD 2-oxydoreductase, EC 1.1.1.18) from Klebsiella pneumoniae (formerly classified taxonomically as Aerobacter aerogenes or Kleb siella aerogenes) was investigated. [4-3H] NAD was enzymatically reduced to [4-3H] NADH with non-labeled myoinositol and myo-inositol dehydrogenase. The stereochemistry of the prochiral center at C4 of the NADH produced was determined. It was found that the label was exclusively located at the (4S) position of the produced NADH. Since the hydrogen transferred from non-labeled myo-inositol to [4-3H] NAD must have entered the opposite of (R) position, myo-inositol dehydrogenase from K. pneumoniae should be classified as an (R) or A-type enzyme with respect to the stereochemistry of the hydrogen transfer to NAD.", "contents": "Chirality of the hydrogen transfer to NAD catalyzed by myo-inositol dehydrogenase from Klebsiella pneumoniae. Chirality, Hydrogen Transfer, myo-Inositol Dehydrogenase. The chirality of the hydrogen transfer to NAD catalyzed by myo-inositol dehydrogenase (myo-Inositol: NAD 2-oxydoreductase, EC 1.1.1.18) from Klebsiella pneumoniae (formerly classified taxonomically as Aerobacter aerogenes or Kleb siella aerogenes) was investigated. [4-3H] NAD was enzymatically reduced to [4-3H] NADH with non-labeled myoinositol and myo-inositol dehydrogenase. The stereochemistry of the prochiral center at C4 of the NADH produced was determined. It was found that the label was exclusively located at the (4S) position of the produced NADH. Since the hydrogen transferred from non-labeled myo-inositol to [4-3H] NAD must have entered the opposite of (R) position, myo-inositol dehydrogenase from K. pneumoniae should be classified as an (R) or A-type enzyme with respect to the stereochemistry of the hydrogen transfer to NAD."}
{"id": "PMID:185838", "title": "[Histochemistry of proteins and their functionally active groups in the skin of the neck and mucous membrane of the oral cavity of white rats in the zone exposed to a helium-neon laser].", "content": "The author made experiments on 49 white rats exposing their cervical skin ano oral cavity mucous membrane to the irradiation beam of a 40 mvt helium-neon laser (lambda 6328A) during 10-15 minutes. The reactive capacity of proteins was found to have intensified and the content of functionally active groups, especially SH. to have increased as well as well as the activity of the cytochromozydase. When the exposition to laser irradiation was raised to 30 minutes pronounced morphohistochemical lesions were noted in the cervical skin and oral cavity mucous membrane. The data received may be useful in clinical practice for the application of low-power laser irradiation of 6328A wave length for stimulation of metabolic processes.", "contents": "[Histochemistry of proteins and their functionally active groups in the skin of the neck and mucous membrane of the oral cavity of white rats in the zone exposed to a helium-neon laser]. The author made experiments on 49 white rats exposing their cervical skin ano oral cavity mucous membrane to the irradiation beam of a 40 mvt helium-neon laser (lambda 6328A) during 10-15 minutes. The reactive capacity of proteins was found to have intensified and the content of functionally active groups, especially SH. to have increased as well as well as the activity of the cytochromozydase. When the exposition to laser irradiation was raised to 30 minutes pronounced morphohistochemical lesions were noted in the cervical skin and oral cavity mucous membrane. The data received may be useful in clinical practice for the application of low-power laser irradiation of 6328A wave length for stimulation of metabolic processes."}
{"id": "PMID:185839", "title": "Cystinosis with crystal-induced synovitis and arthropathy.", "content": "A clinically and experimentally verified intermediary form of cystinosis is described. A 30-year old patient has been examined initially for eye complications confined to the frontal segment of the eye on the cornea and conjunctiva. The joint disease received no attention despite the fact that the motor apparatus of the patient was involved from her childhood. As regards the arthrology, the disease can be classed among crystal-induced synovitis and arthropathy. The lesion of the tubular apparatus of the kidney, which cannot transform vitamin D into its active form, represents an important factor in the genesis of osteoporosis. A description of the intermediary from of cystinosis with eye, kidney and joint symptoms was not found in the literature.", "contents": "Cystinosis with crystal-induced synovitis and arthropathy. A clinically and experimentally verified intermediary form of cystinosis is described. A 30-year old patient has been examined initially for eye complications confined to the frontal segment of the eye on the cornea and conjunctiva. The joint disease received no attention despite the fact that the motor apparatus of the patient was involved from her childhood. As regards the arthrology, the disease can be classed among crystal-induced synovitis and arthropathy. The lesion of the tubular apparatus of the kidney, which cannot transform vitamin D into its active form, represents an important factor in the genesis of osteoporosis. A description of the intermediary from of cystinosis with eye, kidney and joint symptoms was not found in the literature."}
{"id": "PMID:185845", "title": "[Effiency in surgery (author's transl)].", "content": "Increase in the cost of medical care force us to adopt \"medical rationalisation\" instead of as previously \"hospital rationalisation\". This medical rationalisation constitutes a new, well-thought out way of putting questions about diagnosis, therapy and after-care. We must abandon the opinion that the prestige of a surgical department rests in the number of beds. Instead we must use other yardsticks such as the greater use of ambulant care, the shortest hospital stay for routine operations, the shortest preoperative waiting times and an increased operation frequency. Moreover, we need a diagnosis fixed from the start, a large enough operation capacity and sufficient possibilities for postoperative care, stringency in keeping agreed admittances and discharges as regards elective routine surgery and intimate co-operation between doctors, hospital economists, nursing staff and other experts.", "contents": "[Effiency in surgery (author's transl)]. Increase in the cost of medical care force us to adopt \"medical rationalisation\" instead of as previously \"hospital rationalisation\". This medical rationalisation constitutes a new, well-thought out way of putting questions about diagnosis, therapy and after-care. We must abandon the opinion that the prestige of a surgical department rests in the number of beds. Instead we must use other yardsticks such as the greater use of ambulant care, the shortest hospital stay for routine operations, the shortest preoperative waiting times and an increased operation frequency. Moreover, we need a diagnosis fixed from the start, a large enough operation capacity and sufficient possibilities for postoperative care, stringency in keeping agreed admittances and discharges as regards elective routine surgery and intimate co-operation between doctors, hospital economists, nursing staff and other experts."}
{"id": "PMID:185850", "title": "Ultrastructure of lipopolysaccharides of Yersinia enterocolitica, Salmonella typhimurium and Escherichia coli.", "content": "The fine structure of isolated lipopolysaccharides (LPS) from the rough and smooth form of an Yersinia enterocolitica strain (Ye 75 R/Ye 75 S) and from smooth forms of Salmonella typhimurium (S 1010) and Escherichia coli (Essen) were examined electron-microscopically by negative staining. Partial denaturation of LPS in Tris-buffer with acid and/or polymyxin B treatment revealed a common structure of strandlike LPS. Electron-microscopically, LPS-strands were found to consist of two identical sub-strands which form a double helix. High resolution electron microscopy permitted the identification of a total of four longitudinal fibrils (diameter approximately 20 A); therefore, each sub-strand consists of two longitudinal fibrils. These results were correlated with those obtained with positive staining procedure and chemical fixation technique. The development of the \"double-track\"-profile of the outer membrane was interpreted to result from the projection of the helical longitudinal fibrils into the image plane.", "contents": "Ultrastructure of lipopolysaccharides of Yersinia enterocolitica, Salmonella typhimurium and Escherichia coli. The fine structure of isolated lipopolysaccharides (LPS) from the rough and smooth form of an Yersinia enterocolitica strain (Ye 75 R/Ye 75 S) and from smooth forms of Salmonella typhimurium (S 1010) and Escherichia coli (Essen) were examined electron-microscopically by negative staining. Partial denaturation of LPS in Tris-buffer with acid and/or polymyxin B treatment revealed a common structure of strandlike LPS. Electron-microscopically, LPS-strands were found to consist of two identical sub-strands which form a double helix. High resolution electron microscopy permitted the identification of a total of four longitudinal fibrils (diameter approximately 20 A); therefore, each sub-strand consists of two longitudinal fibrils. These results were correlated with those obtained with positive staining procedure and chemical fixation technique. The development of the \"double-track\"-profile of the outer membrane was interpreted to result from the projection of the helical longitudinal fibrils into the image plane."}
{"id": "PMID:185851", "title": "[Studies on virus inactivation by chlorine during water disinfection (author's transl)].", "content": "The studies described indicate a potential for water-borne transmission of viral diseases and the problems involved in virus inactivation by means of water chlorination. In contrast to the amount of free chlorine, the value of the oxidation-reduction potential (ORP) was found to be a criterion of virus inactivation. For virus inactivation, higher ORP values and longer periods of contact than for the killing of bacteria, respectively, were found to be necessary. To ensure the inactivation of poliovirus in water contaminated with organic substances, an ORP of + 780 mV (0.3-0.6 mg/l free chlorine) should be maintained for 15-30 min. Adenovirus has shown an almost identical resistance to inactivation. Possibilities for utilizing the mechanism of virus inactivation by the action of chemical disinfectants are discussed.", "contents": "[Studies on virus inactivation by chlorine during water disinfection (author's transl)]. The studies described indicate a potential for water-borne transmission of viral diseases and the problems involved in virus inactivation by means of water chlorination. In contrast to the amount of free chlorine, the value of the oxidation-reduction potential (ORP) was found to be a criterion of virus inactivation. For virus inactivation, higher ORP values and longer periods of contact than for the killing of bacteria, respectively, were found to be necessary. To ensure the inactivation of poliovirus in water contaminated with organic substances, an ORP of + 780 mV (0.3-0.6 mg/l free chlorine) should be maintained for 15-30 min. Adenovirus has shown an almost identical resistance to inactivation. Possibilities for utilizing the mechanism of virus inactivation by the action of chemical disinfectants are discussed."}
{"id": "PMID:185852", "title": "[Results of animal experiments concerning the carcinogenic effect of fibrous dusts and their interpretation with regard to the carcinogenesis in humans (author's transl)].", "content": "After reviewing the hypotheses about the pathogenesis of asbestos-induced malignant tumours we report about experimental data on animals. A high incidence of tumours (most of them mesotheliomas) was induced in rats by intraperitoneal injection of fibrous dusts (chrysotile, palygorscite, crocidolite, glass fibres, nemalite). Treatment with 8 types of granular dusts led though applicating a high dosage (50--100 mg) to neoplasms in only a small percentage of animals. After intraperitoneal application of 2 mg of chrysotile, crocidolite or glass fibres a tumour incidence in a range from 16% to 38% was observed and fibrous reaction was slight. 100 mg of milled chrysotile with relative short fibres (99.8% less than 5 mum, 99.5% less than 3 mum) caused no asbestosis, nevertheless tumours developed in 32% of the rats. Intraperitoneal injection of fibrous dusts also induced mesotheliomas in mice, however not in Syrian hamsters and guinea pigs. Our results point out that the fibrous shape of asbestos dust causes its carcinogenic effect and that furthermore other fibrous dusts can also lead to tumours. Prerequisites are an adequate measure of the fibres and their constancy in the tissue. For these two parameters no exact dates exist. It is estimated that a fibre with a diameter less than 1 mum and a length less than 3 mum exert a cancerogenic effect. Furthermore, a sequence of other factors has an importance for the dose-effect relationship of fibrous dusts. Material of the fibres plays a role in so far it defines the effect producing amount of fibres. The relevance of the results of animal experiments to man is discussed especially with regard to the cancerogenic effect of glass fibres.", "contents": "[Results of animal experiments concerning the carcinogenic effect of fibrous dusts and their interpretation with regard to the carcinogenesis in humans (author's transl)]. After reviewing the hypotheses about the pathogenesis of asbestos-induced malignant tumours we report about experimental data on animals. A high incidence of tumours (most of them mesotheliomas) was induced in rats by intraperitoneal injection of fibrous dusts (chrysotile, palygorscite, crocidolite, glass fibres, nemalite). Treatment with 8 types of granular dusts led though applicating a high dosage (50--100 mg) to neoplasms in only a small percentage of animals. After intraperitoneal application of 2 mg of chrysotile, crocidolite or glass fibres a tumour incidence in a range from 16% to 38% was observed and fibrous reaction was slight. 100 mg of milled chrysotile with relative short fibres (99.8% less than 5 mum, 99.5% less than 3 mum) caused no asbestosis, nevertheless tumours developed in 32% of the rats. Intraperitoneal injection of fibrous dusts also induced mesotheliomas in mice, however not in Syrian hamsters and guinea pigs. Our results point out that the fibrous shape of asbestos dust causes its carcinogenic effect and that furthermore other fibrous dusts can also lead to tumours. Prerequisites are an adequate measure of the fibres and their constancy in the tissue. For these two parameters no exact dates exist. It is estimated that a fibre with a diameter less than 1 mum and a length less than 3 mum exert a cancerogenic effect. Furthermore, a sequence of other factors has an importance for the dose-effect relationship of fibrous dusts. Material of the fibres plays a role in so far it defines the effect producing amount of fibres. The relevance of the results of animal experiments to man is discussed especially with regard to the cancerogenic effect of glass fibres."}
{"id": "PMID:185856", "title": "[Effect of the site of microbial aerosol application on the pathogenesis and clinical picture of aerosol infection].", "content": "On the basis of experimental and clinical study of infections with the aerosol mechanism of infection there was revealed a relationship between the fractional-dispersive composition of the microbial aerosol, the porta of infection and the clinico-pathogenetic peculiarities of the course of the disease. On the example of tularemia, plague and other nosological forms it was demonstrated that coarse-dispersive aerosol caused development of oculo-bubonic and anginous-bubonic form of the disease, whereas the high-dispersive aerosol led to the appearance of primary pneumonia. In experimental aerosol infection with the causative agents in which the infection under natural conditions is not air-borne (botulism, American horse encephalo-myelitis, etc.) specific disease as a rule develops without any primary affection of the respiratory organs.", "contents": "[Effect of the site of microbial aerosol application on the pathogenesis and clinical picture of aerosol infection]. On the basis of experimental and clinical study of infections with the aerosol mechanism of infection there was revealed a relationship between the fractional-dispersive composition of the microbial aerosol, the porta of infection and the clinico-pathogenetic peculiarities of the course of the disease. On the example of tularemia, plague and other nosological forms it was demonstrated that coarse-dispersive aerosol caused development of oculo-bubonic and anginous-bubonic form of the disease, whereas the high-dispersive aerosol led to the appearance of primary pneumonia. In experimental aerosol infection with the causative agents in which the infection under natural conditions is not air-borne (botulism, American horse encephalo-myelitis, etc.) specific disease as a rule develops without any primary affection of the respiratory organs."}
{"id": "PMID:185857", "title": "[The coxsackievirus-infected mouse: an animal model for the study of virus myocarditis].", "content": "Basing on the experimental infection of adult mice with coxsackie virus A9 reported by Lerner in 1965 and the successful cultivation of the virus from the hearts of experimental animals, a model for studying virus myocarditis is proposed. By a combination of factors favouring the infection (age of the animals above 1 year, physical load prior to infection by repeated swimming) a high virus re-isolation rate was achieved. Cultivation of the virus from the mouse heart was possible on the 3rd day p.i. in 81%, on the 6th day in 71%, on the 9th day in 31%, and on the 12th day in 12% of the cases. In 66% of the animals towards the end of the period of observation a significant increase in few cases is the virus isolated on the 3rd and 6th day p.i. also from the skeletal muscles. The model can be used both for pathogenetic studies on myocardites elicited by cardiotropic viruses and for in vivo testing of antiviral substances.", "contents": "[The coxsackievirus-infected mouse: an animal model for the study of virus myocarditis]. Basing on the experimental infection of adult mice with coxsackie virus A9 reported by Lerner in 1965 and the successful cultivation of the virus from the hearts of experimental animals, a model for studying virus myocarditis is proposed. By a combination of factors favouring the infection (age of the animals above 1 year, physical load prior to infection by repeated swimming) a high virus re-isolation rate was achieved. Cultivation of the virus from the mouse heart was possible on the 3rd day p.i. in 81%, on the 6th day in 71%, on the 9th day in 31%, and on the 12th day in 12% of the cases. In 66% of the animals towards the end of the period of observation a significant increase in few cases is the virus isolated on the 3rd and 6th day p.i. also from the skeletal muscles. The model can be used both for pathogenetic studies on myocardites elicited by cardiotropic viruses and for in vivo testing of antiviral substances."}
{"id": "PMID:185853", "title": "[Glycogen synthetase and fructose diphosphatase activity in the tussues of mollusks (Mytilus galloprovincialis) and crustacenas (Balanus improvisus, Carcinus maenas)].", "content": "The level of the activity of the enzymes studied is rather similar in all the species investigated, being the highest in muscles and gills. Seasonal changes in the activity of the enzymes in mussel tissues are closely related to reproductive periods and reflect changes in the level of glycogen synthesis.", "contents": "[Glycogen synthetase and fructose diphosphatase activity in the tussues of mollusks (Mytilus galloprovincialis) and crustacenas (Balanus improvisus, Carcinus maenas)]. The level of the activity of the enzymes studied is rather similar in all the species investigated, being the highest in muscles and gills. Seasonal changes in the activity of the enzymes in mussel tissues are closely related to reproductive periods and reflect changes in the level of glycogen synthesis."}
{"id": "PMID:185859", "title": "Effect of arecoline on synaptosomal K+-phosphatase and (Na+ + K+)-ATPase.", "content": "Synaptosomal fractions and synaptosomal membranes from rat brain tissue were prepared and characterized enzymatically. Arecoline increased both the activity of K+-phosphatase in incubated synaptosomal fractions and the (Na+ + K+)-ATPase activity of synaptosomal membranes by 40% and 78%, respectively. This activation of ion transport processes is believed to be associated with increased ACh synthesis produced by arecoline.", "contents": "Effect of arecoline on synaptosomal K+-phosphatase and (Na+ + K+)-ATPase. Synaptosomal fractions and synaptosomal membranes from rat brain tissue were prepared and characterized enzymatically. Arecoline increased both the activity of K+-phosphatase in incubated synaptosomal fractions and the (Na+ + K+)-ATPase activity of synaptosomal membranes by 40% and 78%, respectively. This activation of ion transport processes is believed to be associated with increased ACh synthesis produced by arecoline."}
{"id": "PMID:185855", "title": "[Seasonal changes in the reaction of the hypophyseal-adrenal system to adrenomimetics in the suslik Citellus erythrogenys].", "content": "Studies have been made on the reaction of the hypophysial-adrenal system to the injection of adrenalin and novodrin to the ground squirrel C. erythrogenys at various seasons of year and at different functional conditions of the animals. Together with seasonal variations in the basal level of corticosteroids in the peripheral blood, seasonal changes in the reaction of non-hibernating animals to adrenomimetics were found. Stimulating effect of the adrenomimetics was higher at spring, immediately after awakening, being significantly lower in summer and being absent before the onset of hibernation. At the same time, the sensivity of the adrenal cortex to ACTH was relatively high. Presumably, seasonal changes in the reaction of the hypophysial-adrenal system in the ground squirrels to adrenomimetics are associated either with changes in the sensitivity of the adrenoreceptors, or with changes in the reactivity of the central part of the hypothalamo-hypophysial-adrenal system.", "contents": "[Seasonal changes in the reaction of the hypophyseal-adrenal system to adrenomimetics in the suslik Citellus erythrogenys]. Studies have been made on the reaction of the hypophysial-adrenal system to the injection of adrenalin and novodrin to the ground squirrel C. erythrogenys at various seasons of year and at different functional conditions of the animals. Together with seasonal variations in the basal level of corticosteroids in the peripheral blood, seasonal changes in the reaction of non-hibernating animals to adrenomimetics were found. Stimulating effect of the adrenomimetics was higher at spring, immediately after awakening, being significantly lower in summer and being absent before the onset of hibernation. At the same time, the sensivity of the adrenal cortex to ACTH was relatively high. Presumably, seasonal changes in the reaction of the hypophysial-adrenal system in the ground squirrels to adrenomimetics are associated either with changes in the sensitivity of the adrenoreceptors, or with changes in the reactivity of the central part of the hypothalamo-hypophysial-adrenal system."}
{"id": "PMID:185860", "title": "[Discriminant-analytic structure-effect relationship of qualitative biological data. Virostatic effect of isatin-beta-isothiosemicarbazones].", "content": "\"Yes/No\" results from the plaque-diffusion inhibition test concerning the virostatic activity of substituted isatin-beta-isothiosemicarbazones against mengo- and vaccinia-viruses can be described discriminant analytically by means of simple substituent constants. The discriminant analysis permits quantitative structure-activity analysis of qualitative and semi-quantitative test data, thus offering a chance for theoretical synthesis optimization already at the level of rough screening.", "contents": "[Discriminant-analytic structure-effect relationship of qualitative biological data. Virostatic effect of isatin-beta-isothiosemicarbazones]. \"Yes/No\" results from the plaque-diffusion inhibition test concerning the virostatic activity of substituted isatin-beta-isothiosemicarbazones against mengo- and vaccinia-viruses can be described discriminant analytically by means of simple substituent constants. The discriminant analysis permits quantitative structure-activity analysis of qualitative and semi-quantitative test data, thus offering a chance for theoretical synthesis optimization already at the level of rough screening."}
{"id": "PMID:185861", "title": "[The effect of diisopropylfluorphosphate on the adenylate cyclase activity and the 3',5'-AMP content of myocardium and brain].", "content": "Adenylate cyclase [ATP-pyrophosphatelyase (cyclizing) EC 4.6.1.1.] from ventricular muscles and the cerebrum of rats can be inhibited by diisopropylphosphofluoridate (DFP) and paraxone in concentrations from 10(-7) - 10(-9)M, and by dimethoate in concentrations from 10(-5) - 10(-7)M. The cAMP content in the heart diminished after i.p. 1.44 mg/kg DFP by 59.9%, and in the cerebrum by 68.2%. The depletion of cAMP caused by double LD50 DFP in the rat heart can be influenced neither by atropine alone, nor in combination with TMB-4. The results are discussed with regard to a possible action mechanism.", "contents": "[The effect of diisopropylfluorphosphate on the adenylate cyclase activity and the 3',5'-AMP content of myocardium and brain]. Adenylate cyclase [ATP-pyrophosphatelyase (cyclizing) EC 4.6.1.1.] from ventricular muscles and the cerebrum of rats can be inhibited by diisopropylphosphofluoridate (DFP) and paraxone in concentrations from 10(-7) - 10(-9)M, and by dimethoate in concentrations from 10(-5) - 10(-7)M. The cAMP content in the heart diminished after i.p. 1.44 mg/kg DFP by 59.9%, and in the cerebrum by 68.2%. The depletion of cAMP caused by double LD50 DFP in the rat heart can be influenced neither by atropine alone, nor in combination with TMB-4. The results are discussed with regard to a possible action mechanism."}
{"id": "PMID:185862", "title": "Stimulation of Ca2+ uptake by cyclic AMP and protein kinase in sarcoplasmic reticulum-rich and sarcolemma-rich microsomal fractions from rabbit heart.", "content": "The effect of cyclic AMP on Ca2+ uptake by rabbit heart microsomal vesicular fractions representing mainly fragments of either sarcoplasmic reticulum or sarcolemma was investigated in the presence and absence of soluble cardiac protein kinase and with microsomes prephosphorylated by cyclic AMP-dependent protein kinase. The acceleration of oxalate-promoted Ca2+ uptake by fragmented sarcoplasmic reticulum following cyclic AMP-dependent membrane protein phosphorylation, observed by other authors, was confirmed. In addition it was found that the acceleration was greatest at pH 7.2 and almost negligible at pH 6.0 and pH 7.8. A very marked increase in Ca2+ uptake by cyclic AMP-dependent membrane protein phosphorylation was observed in the presence of boric acid, a reversible inhibitor of Ca2+ uptake. In addition to the microsomal fraction thought to represent mainly fragments of the sarcoplasmic reticulum, the effect of protein kinase and cyclic AMP on Ca2+ uptake was investigated in a cardiac sarcolemma-enriched membrane fraction. Ca2+ uptake by sarcolemmal vesicles, unlike Ca2+ uptake by sarcoplasmic reticulum vesicles, was inhibited by low doses of digitoxin. The acceleration of oxalate-promoted Ca2+ uptake by cyclic AMP and soluble cardiac protein kinase, however, was quite similar to what was seen in preparations of fragmented sarcoplasmic reticulum, which suggests that it may reflect an acceleration of active Ca2+ transport across the myocardial cell surface membrane.", "contents": "Stimulation of Ca2+ uptake by cyclic AMP and protein kinase in sarcoplasmic reticulum-rich and sarcolemma-rich microsomal fractions from rabbit heart. The effect of cyclic AMP on Ca2+ uptake by rabbit heart microsomal vesicular fractions representing mainly fragments of either sarcoplasmic reticulum or sarcolemma was investigated in the presence and absence of soluble cardiac protein kinase and with microsomes prephosphorylated by cyclic AMP-dependent protein kinase. The acceleration of oxalate-promoted Ca2+ uptake by fragmented sarcoplasmic reticulum following cyclic AMP-dependent membrane protein phosphorylation, observed by other authors, was confirmed. In addition it was found that the acceleration was greatest at pH 7.2 and almost negligible at pH 6.0 and pH 7.8. A very marked increase in Ca2+ uptake by cyclic AMP-dependent membrane protein phosphorylation was observed in the presence of boric acid, a reversible inhibitor of Ca2+ uptake. In addition to the microsomal fraction thought to represent mainly fragments of the sarcoplasmic reticulum, the effect of protein kinase and cyclic AMP on Ca2+ uptake was investigated in a cardiac sarcolemma-enriched membrane fraction. Ca2+ uptake by sarcolemmal vesicles, unlike Ca2+ uptake by sarcoplasmic reticulum vesicles, was inhibited by low doses of digitoxin. The acceleration of oxalate-promoted Ca2+ uptake by cyclic AMP and soluble cardiac protein kinase, however, was quite similar to what was seen in preparations of fragmented sarcoplasmic reticulum, which suggests that it may reflect an acceleration of active Ca2+ transport across the myocardial cell surface membrane."}
{"id": "PMID:185863", "title": "An improved protein binding assay for guanosine-3',5'-monophosphate using a binding protein from the pupa of the silkmoth, Bombyx mori L.", "content": "A modification of the protein binding assay for cyclic guanosine-3',5'-monophosphate (cyclic GMP) is described that is more sensitive and less subject to interference by cyclic AMP than are previously published protein binding methods. The assay employs a purified binding protein from the fat body of the pupa of the common silkmoth, Bombyx mori. The dissociation constant of the binding protein for cyclic GMP is 4.3 nM. A protein kinase modulator protein isolated from the same species increases the binding affinity and capacity of the cyclic GMP binding protein and can be used to advantage in the assay for cyclic GMP. As little as 0.1 pmoles of cyclic GMP can be detected by this procedure. Changes in the level of cyclic GMP in the frog heart during the cardiac cycle were determined by means of the new assay.", "contents": "An improved protein binding assay for guanosine-3',5'-monophosphate using a binding protein from the pupa of the silkmoth, Bombyx mori L. A modification of the protein binding assay for cyclic guanosine-3',5'-monophosphate (cyclic GMP) is described that is more sensitive and less subject to interference by cyclic AMP than are previously published protein binding methods. The assay employs a purified binding protein from the fat body of the pupa of the common silkmoth, Bombyx mori. The dissociation constant of the binding protein for cyclic GMP is 4.3 nM. A protein kinase modulator protein isolated from the same species increases the binding affinity and capacity of the cyclic GMP binding protein and can be used to advantage in the assay for cyclic GMP. As little as 0.1 pmoles of cyclic GMP can be detected by this procedure. Changes in the level of cyclic GMP in the frog heart during the cardiac cycle were determined by means of the new assay."}
{"id": "PMID:185865", "title": "[The systemic fungicide tridermorph as an inhibitor of the respiratory chain of electron transfer particles from beef heart mitochondria].", "content": "Tridemorph (N-tridecyl-2,6-dimethylmorpholine) inhibits both the NADH-oxidase and the succinate-cytochrome c oxydoreductase system of non-phosphorylating electron transfer particles from beef heart. The concentration required for half-inhibition amounted to 3,4 muM and 24 muM respectively. Two different sites of action in the respiratory chain could be localized by means of difference spectroscopy and measurements of enzymic activities in various partial systems. The inhibition of the NADH-ubiquinone oxydoreductase activity as well as the suppression of the NADH-induced reduction of all cytochromes on the one hand and the insensitivity of the NADH-ferricyanide oxydoreductase system on the other argue in favour of a site of action similar to rotenone. The partial suppression of the succinate-induced reduction of cytochrome b with simultaneous complete inhibition of the reduction of the other cytochromes indicate an additional site of action analogous to antimycin A. Both inhibitory actions appeared instantaneously after the addition of tridemorph and were counteracted by serum albumin. Furthermore, tridemorph inhibited the oxydation of external ferrocytochrome c but not that of ascorbate/tetra-methyl-p-phenylene-diamine-HCI (TMPID) showing that it is not a true inhibitor of the cytochrome oxidase. The TMPD-induced bypass of the succinate oxidation was inhibited as well. The possible role of the inhibition of the main pathway of the respiratory chain for the fungicidal action of tridemorph is discussed.", "contents": "[The systemic fungicide tridermorph as an inhibitor of the respiratory chain of electron transfer particles from beef heart mitochondria]. Tridemorph (N-tridecyl-2,6-dimethylmorpholine) inhibits both the NADH-oxidase and the succinate-cytochrome c oxydoreductase system of non-phosphorylating electron transfer particles from beef heart. The concentration required for half-inhibition amounted to 3,4 muM and 24 muM respectively. Two different sites of action in the respiratory chain could be localized by means of difference spectroscopy and measurements of enzymic activities in various partial systems. The inhibition of the NADH-ubiquinone oxydoreductase activity as well as the suppression of the NADH-induced reduction of all cytochromes on the one hand and the insensitivity of the NADH-ferricyanide oxydoreductase system on the other argue in favour of a site of action similar to rotenone. The partial suppression of the succinate-induced reduction of cytochrome b with simultaneous complete inhibition of the reduction of the other cytochromes indicate an additional site of action analogous to antimycin A. Both inhibitory actions appeared instantaneously after the addition of tridemorph and were counteracted by serum albumin. Furthermore, tridemorph inhibited the oxydation of external ferrocytochrome c but not that of ascorbate/tetra-methyl-p-phenylene-diamine-HCI (TMPID) showing that it is not a true inhibitor of the cytochrome oxidase. The TMPD-induced bypass of the succinate oxidation was inhibited as well. The possible role of the inhibition of the main pathway of the respiratory chain for the fungicidal action of tridemorph is discussed."}
{"id": "PMID:185866", "title": "Effect of salicylate and adrenocorticotropin on the hepatic and serum cholesterol in catfish, Heteropneustes fossilis (Bloch).", "content": "A single injection of salicylate or salicylate plus ACTH was able to lower the hepatic cholesterol content within one hour after the treatment. However, their daily injection for eight days caused significant rise in the hepatic cholesterol. ACTH alone could not significantly alter the liver cholesterol content after similar treatment. A single injection of salicylate produced hypocholesterolemia within one and three hours after the treatment. ACTH or salicylate plus ACTH also brought about 50 per cent reduction in serum cholesterol level from its initial control value within one hour. Similar treatments, however, raised the serum cholesterol after three hours. The rise in the serum cholesterol level was about twofold in animals five hours after salicylate plus ACTH treatment. Daily administration of salicylate, ACTH or salicylate plus ACTH for eight days caused, however, hypocholesterolemia.", "contents": "Effect of salicylate and adrenocorticotropin on the hepatic and serum cholesterol in catfish, Heteropneustes fossilis (Bloch). A single injection of salicylate or salicylate plus ACTH was able to lower the hepatic cholesterol content within one hour after the treatment. However, their daily injection for eight days caused significant rise in the hepatic cholesterol. ACTH alone could not significantly alter the liver cholesterol content after similar treatment. A single injection of salicylate produced hypocholesterolemia within one and three hours after the treatment. ACTH or salicylate plus ACTH also brought about 50 per cent reduction in serum cholesterol level from its initial control value within one hour. Similar treatments, however, raised the serum cholesterol after three hours. The rise in the serum cholesterol level was about twofold in animals five hours after salicylate plus ACTH treatment. Daily administration of salicylate, ACTH or salicylate plus ACTH for eight days caused, however, hypocholesterolemia."}
{"id": "PMID:185867", "title": "Effects of ethosuximide upon psychomotor responses and electromyographic parameters of healthy individuals.", "content": "The purpose of this paper was to investigate the effects of anticonvulsant ethosuximide upon physiological parameters, psychomotor reactions and electromyographic criteria. Ethosuximide increased the reaction times to flashes and the choice reaction time in most subjects, often provoked a greater amount of errors during choice reactions and decreased the average heart frequency. The functional activation during the tasks was diminished. The EEG showed no marked qualitative or quantitative changes. Ethosuximide reduced the maximum conduction velocity of the motor nerve and changed the action potential duration but not the action potential shape. There is no exact parallelism between the increase in reaction time and decrease of nerve conduction velocity. The drug effect upon psychomotor reactions seems to be caused by reduction of vigilance and an inhibitory effect upon the individual's motor responsiveness. Like other anticonvulsants, ethosuximide may alter the electrical properties of all excitable membranes and, by this ubiquitous site of action, exerts the described effects.", "contents": "Effects of ethosuximide upon psychomotor responses and electromyographic parameters of healthy individuals. The purpose of this paper was to investigate the effects of anticonvulsant ethosuximide upon physiological parameters, psychomotor reactions and electromyographic criteria. Ethosuximide increased the reaction times to flashes and the choice reaction time in most subjects, often provoked a greater amount of errors during choice reactions and decreased the average heart frequency. The functional activation during the tasks was diminished. The EEG showed no marked qualitative or quantitative changes. Ethosuximide reduced the maximum conduction velocity of the motor nerve and changed the action potential duration but not the action potential shape. There is no exact parallelism between the increase in reaction time and decrease of nerve conduction velocity. The drug effect upon psychomotor reactions seems to be caused by reduction of vigilance and an inhibitory effect upon the individual's motor responsiveness. Like other anticonvulsants, ethosuximide may alter the electrical properties of all excitable membranes and, by this ubiquitous site of action, exerts the described effects."}
{"id": "PMID:185871", "title": "Existence of big and little forms of luteinizing hormone in human serum.", "content": "Serum fractions from normal subjects obtained by gel chromatography have been investigated using three different assay systems: radioimmunoassay (RIA), radioligand receptor assay (RRA), and testosterone production assay (TPA). The bulk of immunoassayable and \"bioassayable\" LH-activity was found in two fractions differing widely in their molecular size. The slower moving component, designated as \"little\" LH, migrated identical to the radioiodinated pituitary hormone (LER 960) with a molecular weight of about 30,000, while \"big\" LH appeared in an elution volume consistent with a molecular weight range between 140,000 and 180,000. Concordance was seen between the LH-activities measured in all three assay systems. The RRA/RIA ratio varied between 1.6 and 8.9, the RRA/TPA ratio was close to unity. Treatment with 6 M urea and 0.1% mercaptoethanol and also, exposure to different pH values and salt concentrations did not change the elution position of the two LH components. Also, \"big\" and \"little\" LH appeared unaltered after re-filtration and no conversion each other could be found. In another experiment injection of gonadotrophin releasing hormone (Gn-RH) into a male induced a profound shift of LH towards the low molecular weight species. Kinetic uptake studies with \"big\" and \"little\" LH using RRA showed identical affinities to the receptor preparation. Ion exchange chromatography of serum, however, did not give two LH components, indicating no major differences in charge properties. This finding could be confirmed by preparative gel isoelectric focusing. The RRA potencies following gel filtration were in good agreement with that applied to the column, however, the immunological activities exceeded that of loaded by a factor 3-4. A new aspect of serum LH heterogeneity is the finding of a low molecular substance (mol. weight approximately 1000) in the outer dialysate of serum, which has LH like activity in all three assay systems.", "contents": "Existence of big and little forms of luteinizing hormone in human serum. Serum fractions from normal subjects obtained by gel chromatography have been investigated using three different assay systems: radioimmunoassay (RIA), radioligand receptor assay (RRA), and testosterone production assay (TPA). The bulk of immunoassayable and \"bioassayable\" LH-activity was found in two fractions differing widely in their molecular size. The slower moving component, designated as \"little\" LH, migrated identical to the radioiodinated pituitary hormone (LER 960) with a molecular weight of about 30,000, while \"big\" LH appeared in an elution volume consistent with a molecular weight range between 140,000 and 180,000. Concordance was seen between the LH-activities measured in all three assay systems. The RRA/RIA ratio varied between 1.6 and 8.9, the RRA/TPA ratio was close to unity. Treatment with 6 M urea and 0.1% mercaptoethanol and also, exposure to different pH values and salt concentrations did not change the elution position of the two LH components. Also, \"big\" and \"little\" LH appeared unaltered after re-filtration and no conversion each other could be found. In another experiment injection of gonadotrophin releasing hormone (Gn-RH) into a male induced a profound shift of LH towards the low molecular weight species. Kinetic uptake studies with \"big\" and \"little\" LH using RRA showed identical affinities to the receptor preparation. Ion exchange chromatography of serum, however, did not give two LH components, indicating no major differences in charge properties. This finding could be confirmed by preparative gel isoelectric focusing. The RRA potencies following gel filtration were in good agreement with that applied to the column, however, the immunological activities exceeded that of loaded by a factor 3-4. A new aspect of serum LH heterogeneity is the finding of a low molecular substance (mol. weight approximately 1000) in the outer dialysate of serum, which has LH like activity in all three assay systems."}
{"id": "PMID:185872", "title": "A study of insulin receptors in human mononuclear leucocytes.", "content": "Insulin binding sites were demonstrated in human mononuclear leucocytes by use of a technique which includes isolation of mononuclear leucocytes from defibrinated blood and separation of cell bound and free [125I]insulin with silicone oil. The binding was time and temperature dependent. At 15 degrees C equilibrium was reached after 90 min and a plateau maintained for at least 50 min. Incubations were carried out at 4 degrees C, 15 degrees C and 37 degrees C. Maximal binding was obtained at 15 degrees C. The optimum pH for insulin receptor interaction occurred at about 8. [125I]insulin binding to mononuclear leucocytes was demonstrated to be a linear function of cell number concentration over a range of 17-70 X 10(6) X ml-1. The binding was a displaceable function of native insulin concentration. In a group of 21 young healthy persons with normal body weight we found a mean specific cell binding fraction of 1.92 +/- 0.58 (s) X 10(-2). Analysis of the equilibrium between insulin and its receptor revealed an apparent heterogeneity of insulin receptors.", "contents": "A study of insulin receptors in human mononuclear leucocytes. Insulin binding sites were demonstrated in human mononuclear leucocytes by use of a technique which includes isolation of mononuclear leucocytes from defibrinated blood and separation of cell bound and free [125I]insulin with silicone oil. The binding was time and temperature dependent. At 15 degrees C equilibrium was reached after 90 min and a plateau maintained for at least 50 min. Incubations were carried out at 4 degrees C, 15 degrees C and 37 degrees C. Maximal binding was obtained at 15 degrees C. The optimum pH for insulin receptor interaction occurred at about 8. [125I]insulin binding to mononuclear leucocytes was demonstrated to be a linear function of cell number concentration over a range of 17-70 X 10(6) X ml-1. The binding was a displaceable function of native insulin concentration. In a group of 21 young healthy persons with normal body weight we found a mean specific cell binding fraction of 1.92 +/- 0.58 (s) X 10(-2). Analysis of the equilibrium between insulin and its receptor revealed an apparent heterogeneity of insulin receptors."}
{"id": "PMID:185873", "title": "The insulin receptor in normal and obese persons.", "content": "Using [125I]insulin at 172 pmol/1 (1 ng/ml) the binding of insulin to mononuclear leucocytes isolated from peripheral blood was studied. Our present study comprised 21 healthy subjects (22-33 years old, 90-110% of ideal weight) and a comparable group of 22 obese subjects (20-37 years old, minimum 150% of ideal weight). A significant difference in insulin binding was found between the two groups, the mean specific insulin binding fraction in normals being 1.92 +/- 0.58 (s) X 10(-2) and that for the obese 1.19 +/- 0.41 (s) X 10(-2) (P less than 0.01). No correlation was found between body weight and the number of insulin receptors in the obese subjects. However, the number of insulin receptors was negatively correlated to fat cell size (P less than 0.05). Insulin receptors in subjects were also negatively correlated to fasting plasma insulin (P less than 0.05). Insulin receptors were studied in 11 obese subjects before and after 10 days of fasting. A significant increase in the number of insulin receptors was observed with a simultaneous decrease in plasma insulin to normal values. The results indicate that obesity complicated by hyperinsulinism is associated with a decrease in the number of insulin receptors compared with the normal. This finding may in part explain the decreased insulin sensitivity of the hyperinsulinaemic obese.", "contents": "The insulin receptor in normal and obese persons. Using [125I]insulin at 172 pmol/1 (1 ng/ml) the binding of insulin to mononuclear leucocytes isolated from peripheral blood was studied. Our present study comprised 21 healthy subjects (22-33 years old, 90-110% of ideal weight) and a comparable group of 22 obese subjects (20-37 years old, minimum 150% of ideal weight). A significant difference in insulin binding was found between the two groups, the mean specific insulin binding fraction in normals being 1.92 +/- 0.58 (s) X 10(-2) and that for the obese 1.19 +/- 0.41 (s) X 10(-2) (P less than 0.01). No correlation was found between body weight and the number of insulin receptors in the obese subjects. However, the number of insulin receptors was negatively correlated to fat cell size (P less than 0.05). Insulin receptors in subjects were also negatively correlated to fasting plasma insulin (P less than 0.05). Insulin receptors were studied in 11 obese subjects before and after 10 days of fasting. A significant increase in the number of insulin receptors was observed with a simultaneous decrease in plasma insulin to normal values. The results indicate that obesity complicated by hyperinsulinism is associated with a decrease in the number of insulin receptors compared with the normal. This finding may in part explain the decreased insulin sensitivity of the hyperinsulinaemic obese."}
{"id": "PMID:185869", "title": "Cytologic presentation of mammary carcinoma on aspiration biopsy smears.", "content": "Needle aspirates from 598 histologically verified carcinomas of the female breast were reviewed. Four cytologic types were recognized: duct cell, acinic cell, apocrine cell, and mucous cell carcinoma. Duct cell carcinomas were further subdivided into ductal, ductular-acinar, monolayered and dissociated types. The highest ten-year survival rate was found in mucous cell carcinoma, and the lowest ten-year rates in acinic and dissociated duct cell types. The derivation of the mammary carcinomas is discussed on the basis of comparisons with cellular aspirates from benign mammary lesions. It is suggested that ductular-acinar, monolayered, dissociated and acinic cell carcinomas, which comprised about 50 per cent of the tumors originate in the lobular structures of the mammary gland. The problems involved in distinguishing well differentiated forms of the mammary carcinomas from the corresponding benign structures in needle aspirates are also discussed.", "contents": "Cytologic presentation of mammary carcinoma on aspiration biopsy smears. Needle aspirates from 598 histologically verified carcinomas of the female breast were reviewed. Four cytologic types were recognized: duct cell, acinic cell, apocrine cell, and mucous cell carcinoma. Duct cell carcinomas were further subdivided into ductal, ductular-acinar, monolayered and dissociated types. The highest ten-year survival rate was found in mucous cell carcinoma, and the lowest ten-year rates in acinic and dissociated duct cell types. The derivation of the mammary carcinomas is discussed on the basis of comparisons with cellular aspirates from benign mammary lesions. It is suggested that ductular-acinar, monolayered, dissociated and acinic cell carcinomas, which comprised about 50 per cent of the tumors originate in the lobular structures of the mammary gland. The problems involved in distinguishing well differentiated forms of the mammary carcinomas from the corresponding benign structures in needle aspirates are also discussed."}
{"id": "PMID:185874", "title": "Cortisol effect on collagen biosynthesis in embryonic explants and in vitro hydroxylation of protocollagen.", "content": "The effect of increasing doses of hydrocortisone acetate, hydrocortisone phosphoric acid complex, and hydrocortisone sodium succinate on collagen biosynthesis was assayed in two different systems. I. Explants of chicken embryo tibiae showed decreased biosynthesis of [14C]hydroxyproline and total and glycosylated [14C]hydroxylysine under the influence of high doses of hydrocortisone. With the lower doses of hydrocortisone acetate, no effect was noticed. The total uptake of the precursor amino acids followed patterns similar to those of collagen biosynthesis. II. Hydroxylation of [14C]proline labelled protocollagen by protocollagen proline hydroxylase was inhibited by high doses of hydrocortisone acetate, hydrocortisone phosphoric acid complex, and hydrocortisone sodium succinate. III. A decreased diffusion of collagen to the medium with increasing doses of hydrocortisone acetate, hydrocortisone phosphoric acid, and hydrocortisone sodium succinate was noticed. IV. No further hydroxylation of new-synthesized collagen was obtained under the influence of hydrocortisone phosphoric acid and hydrocortisone sodium succinate, when the undialyzable material was used as a substrate for protocollagen proline hydroxylase.", "contents": "Cortisol effect on collagen biosynthesis in embryonic explants and in vitro hydroxylation of protocollagen. The effect of increasing doses of hydrocortisone acetate, hydrocortisone phosphoric acid complex, and hydrocortisone sodium succinate on collagen biosynthesis was assayed in two different systems. I. Explants of chicken embryo tibiae showed decreased biosynthesis of [14C]hydroxyproline and total and glycosylated [14C]hydroxylysine under the influence of high doses of hydrocortisone. With the lower doses of hydrocortisone acetate, no effect was noticed. The total uptake of the precursor amino acids followed patterns similar to those of collagen biosynthesis. II. Hydroxylation of [14C]proline labelled protocollagen by protocollagen proline hydroxylase was inhibited by high doses of hydrocortisone acetate, hydrocortisone phosphoric acid complex, and hydrocortisone sodium succinate. III. A decreased diffusion of collagen to the medium with increasing doses of hydrocortisone acetate, hydrocortisone phosphoric acid, and hydrocortisone sodium succinate was noticed. IV. No further hydroxylation of new-synthesized collagen was obtained under the influence of hydrocortisone phosphoric acid and hydrocortisone sodium succinate, when the undialyzable material was used as a substrate for protocollagen proline hydroxylase."}
{"id": "PMID:185876", "title": "The occurrence of macrophages in the ischaemic rabbit eye.", "content": "Mature macrophages involved in the removal of outer segment material were found between the visual cells and retinal pigment epithelium of the ischaemic rabbit retina. The mature macrophages were evident after only 15 min of ischaemia and the cells became progressively more numerous with increasing periods of ischaemia. A quantitative study was undertaken into the occurrence of the macrophages. These cells were probably of retinal pigment epithelial origin.", "contents": "The occurrence of macrophages in the ischaemic rabbit eye. Mature macrophages involved in the removal of outer segment material were found between the visual cells and retinal pigment epithelium of the ischaemic rabbit retina. The mature macrophages were evident after only 15 min of ischaemia and the cells became progressively more numerous with increasing periods of ischaemia. A quantitative study was undertaken into the occurrence of the macrophages. These cells were probably of retinal pigment epithelial origin."}
{"id": "PMID:185877", "title": "Progressive external ophthalmoplegia. Evidence for a generalised mitochondrial disease with a defect in pyruvate metabolism.", "content": "Muscle biopsies from four patients with chronic progressive external ophthalmoplegia and pigmentary retinopathy with symptoms and signs from other organs were studied by means of light and electron microscopy. Examination revealed a marked proliferation of abnormal mitochondria with a degeneration of both muscle and nerve tissue. Blood levels of lactate and pyruvate were measured and abnormal values of these metabolites were found in the three patients with the most pronounced ultrastructural changes. On the basis of these findings it is suggested that there is a biochemical defect in pyruvate-lactate metabolism which could be responsible for the marked proliferation of the abnormal mitochondria.", "contents": "Progressive external ophthalmoplegia. Evidence for a generalised mitochondrial disease with a defect in pyruvate metabolism. Muscle biopsies from four patients with chronic progressive external ophthalmoplegia and pigmentary retinopathy with symptoms and signs from other organs were studied by means of light and electron microscopy. Examination revealed a marked proliferation of abnormal mitochondria with a degeneration of both muscle and nerve tissue. Blood levels of lactate and pyruvate were measured and abnormal values of these metabolites were found in the three patients with the most pronounced ultrastructural changes. On the basis of these findings it is suggested that there is a biochemical defect in pyruvate-lactate metabolism which could be responsible for the marked proliferation of the abnormal mitochondria."}
{"id": "PMID:185878", "title": "Zonation of the adrenal cortex. III. Distribution of cytochrome P-450 in the zona glomerulosa of the bovine adrenal cortex.", "content": "A microsomal fraction was obtained from the zona glomerulosa of the bovine adrenal cortex. Glucose-6-phosphate activity of the fraction was found to be much lower than that of the liver. Contents of RNA and phospholipids, besides electron microscopic findings, of the fraction also indicate that it is rich in smooth-surfaced endoplasmic reticulum. Distribution of cytochrome P-450 in the zona glomerulosa was studied using various fractions including the microsomal fraction described above. The amount of cytochrome P-450 in mitochondria and that in microsomes were determined to be 0.73 and 0.32 nmoles/mg protein, respectively. The CO-difference spectrum was affected not only by the concentration of added deoxycholate but also by the incubation time after addition. Approximately 40-50% of cytochrome P-450 in the samples were converted to cytochrome P-420 within 20-30 seconds of incubation with deoxycholate.", "contents": "Zonation of the adrenal cortex. III. Distribution of cytochrome P-450 in the zona glomerulosa of the bovine adrenal cortex. A microsomal fraction was obtained from the zona glomerulosa of the bovine adrenal cortex. Glucose-6-phosphate activity of the fraction was found to be much lower than that of the liver. Contents of RNA and phospholipids, besides electron microscopic findings, of the fraction also indicate that it is rich in smooth-surfaced endoplasmic reticulum. Distribution of cytochrome P-450 in the zona glomerulosa was studied using various fractions including the microsomal fraction described above. The amount of cytochrome P-450 in mitochondria and that in microsomes were determined to be 0.73 and 0.32 nmoles/mg protein, respectively. The CO-difference spectrum was affected not only by the concentration of added deoxycholate but also by the incubation time after addition. Approximately 40-50% of cytochrome P-450 in the samples were converted to cytochrome P-420 within 20-30 seconds of incubation with deoxycholate."}
{"id": "PMID:185879", "title": "Heterotransplantation of experimentally induced dog stomach adenocarcinoma to nude mice.", "content": "Heterotransplantation of gastric adenocarcinoma, induced in dog by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) has been attempted to nude mouse. Biopsied materials from Borrmann 3 type carcinoma, which showed signet-ring cell carcinoma at the subcardiac region of a beagle dog, were inoculated into the muscles of the hind legs of BALB/c-nu/nu nude mice. Serial transmission was obtained in 2 lives, so far 4-5 passages. The histological findings of the grafts were mainly poorly differentiated adenocarcinomas.", "contents": "Heterotransplantation of experimentally induced dog stomach adenocarcinoma to nude mice. Heterotransplantation of gastric adenocarcinoma, induced in dog by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) has been attempted to nude mouse. Biopsied materials from Borrmann 3 type carcinoma, which showed signet-ring cell carcinoma at the subcardiac region of a beagle dog, were inoculated into the muscles of the hind legs of BALB/c-nu/nu nude mice. Serial transmission was obtained in 2 lives, so far 4-5 passages. The histological findings of the grafts were mainly poorly differentiated adenocarcinomas."}
{"id": "PMID:185875", "title": "Correlation between serum high density lipoprotein content and liver function during experimental hepatic degeneration and regeneration.", "content": "Intravenous injection of praseodymium nitrate into female Wistar rats results in liver damage. The aim of this study is to investigate the quality of serum high density lipoprotein content as an index for the severity and time course of liver damage and regeneration following the administration of praseodymium. Serum high density lipoprotein content drastically decreases to a minimum after 24 - 48 h, returning to control values after four days. Liver degeneration is characterized by some intracellular parameters, i.e. the nuclear RNA polymerase reactions, the ribosomal protein synthesis, hepatic spermidine concentration and the activities of serum transaminases (GOT, GPT) and the sorbitdehydrogenase. From the data it is evident that the time course of serum high density lipoprotein content follows the intracellular changes closely. Liver regeneration is represented by the ornithin decarboxylase, the deoxycytidylate deaminase, the thymidine kinase activities and the hepatic putrescine content. The time course of these parameters shows that the regeneration reaches a maximum after 3 - 4 days. In the serum, high density lipoprotein content reflects this process by returning to control values. From our data we conclude that serum high density lipoprotein content after i.v. administration of praseodymium can be considered as an expression of the functional state of the liver.", "contents": "Correlation between serum high density lipoprotein content and liver function during experimental hepatic degeneration and regeneration. Intravenous injection of praseodymium nitrate into female Wistar rats results in liver damage. The aim of this study is to investigate the quality of serum high density lipoprotein content as an index for the severity and time course of liver damage and regeneration following the administration of praseodymium. Serum high density lipoprotein content drastically decreases to a minimum after 24 - 48 h, returning to control values after four days. Liver degeneration is characterized by some intracellular parameters, i.e. the nuclear RNA polymerase reactions, the ribosomal protein synthesis, hepatic spermidine concentration and the activities of serum transaminases (GOT, GPT) and the sorbitdehydrogenase. From the data it is evident that the time course of serum high density lipoprotein content follows the intracellular changes closely. Liver regeneration is represented by the ornithin decarboxylase, the deoxycytidylate deaminase, the thymidine kinase activities and the hepatic putrescine content. The time course of these parameters shows that the regeneration reaches a maximum after 3 - 4 days. In the serum, high density lipoprotein content reflects this process by returning to control values. From our data we conclude that serum high density lipoprotein content after i.v. administration of praseodymium can be considered as an expression of the functional state of the liver."}
{"id": "PMID:185880", "title": "Ultrastructural features of malignant fibrous histiocytoma of bone.", "content": "Five cases of malignant fibrous histiocytoma originating in the femur and tibia, sometimes with local recurrences, are reported. Histological and clinical characteristics of this lesion were similar to those in soft tissues with the same disease. The present histiocytomas were observed by electron microscopy and shown to consist of 5 types of neoplastic cells which were regarded as undifferentiated cells, histiocyte-like cells, which were predominating, fibroblast-like cells, multinucleated giant cells and xanthomatous cells. These findings led us to confirm the existence of malignant fibrous histiocytoma originating in bone as well as in soft tissues.", "contents": "Ultrastructural features of malignant fibrous histiocytoma of bone. Five cases of malignant fibrous histiocytoma originating in the femur and tibia, sometimes with local recurrences, are reported. Histological and clinical characteristics of this lesion were similar to those in soft tissues with the same disease. The present histiocytomas were observed by electron microscopy and shown to consist of 5 types of neoplastic cells which were regarded as undifferentiated cells, histiocyte-like cells, which were predominating, fibroblast-like cells, multinucleated giant cells and xanthomatous cells. These findings led us to confirm the existence of malignant fibrous histiocytoma originating in bone as well as in soft tissues."}
{"id": "PMID:185883", "title": "Kidney size and growth in unilateral renal agenesis and in the remaining kidney following nephrectomy for Wilms' tumor.", "content": "The kidney size and renal growth were determined in unilateral renal agenesis and in the remaining kidney following nephrectomy for Wilms' tumor. The ultimate length of 98 per cent of the functioning kidneys in renal agenesis is expected not to exceed +5.6 SD. In the tumor series the corresponding figure is +4.2 SD.", "contents": "Kidney size and growth in unilateral renal agenesis and in the remaining kidney following nephrectomy for Wilms' tumor. The kidney size and renal growth were determined in unilateral renal agenesis and in the remaining kidney following nephrectomy for Wilms' tumor. The ultimate length of 98 per cent of the functioning kidneys in renal agenesis is expected not to exceed +5.6 SD. In the tumor series the corresponding figure is +4.2 SD."}
{"id": "PMID:185885", "title": "Changes in the adrenergic control and the rate of lipolysis of isolated human adipose tissue during fasting and after re-feeding.", "content": "The influence of changes in nutritional state on lipid mobilization has been investigated, using subcutaneous fat portions removed from 8 obese patients submitted to fasting for one week. The maximal rise in the tissue level of cyclic AMP (cAMP) and the rate of glycerol release were determined when adipose tissue was exposed to noradrenaline (6 X 10(-6) mol/1), isopropylnoradrenaline (6 X 10 (-6) mol/1) or none of the agents (basal medium). Fasting resulted in significant increases in the tissue level of cAMP and the rate of lipolysis in adipose tissue unexposed to lipolytic agents. Noradrenaline decreased the level of cAMP, in contrast to isopropylnoradrenaline, and significantly inhibited the rate of lipolysis during fasting. These noradrenaline effects were abolished by the simultaneous presence of phentolamine (13 mmol/1) in the incubation medium. Re-feeding with Meritene for one day resulted in a diminished rate of basal lipolysis, whereas the cAMP level was unaffected. The response of the cAMP accumulation to isopropylnoradrenaline was further augmented by re-feeding. Noradrenaline produced a significant rise in the level of cAMP and significantly stimulated the rate of glycerol production. It is concluded that the nutritional changes are of significance for the adrenergic regulation of lipolysis as indicated by the response of cAMP to the catecholamines. In pharmacological terms, fasting for one week resulted in increased alpha-as well as beta-adrenergic responsiveness. Increased basal lipolysis during fasting may be related to an increased level of cAMP or a direct activation of lipase.", "contents": "Changes in the adrenergic control and the rate of lipolysis of isolated human adipose tissue during fasting and after re-feeding. The influence of changes in nutritional state on lipid mobilization has been investigated, using subcutaneous fat portions removed from 8 obese patients submitted to fasting for one week. The maximal rise in the tissue level of cyclic AMP (cAMP) and the rate of glycerol release were determined when adipose tissue was exposed to noradrenaline (6 X 10(-6) mol/1), isopropylnoradrenaline (6 X 10 (-6) mol/1) or none of the agents (basal medium). Fasting resulted in significant increases in the tissue level of cAMP and the rate of lipolysis in adipose tissue unexposed to lipolytic agents. Noradrenaline decreased the level of cAMP, in contrast to isopropylnoradrenaline, and significantly inhibited the rate of lipolysis during fasting. These noradrenaline effects were abolished by the simultaneous presence of phentolamine (13 mmol/1) in the incubation medium. Re-feeding with Meritene for one day resulted in a diminished rate of basal lipolysis, whereas the cAMP level was unaffected. The response of the cAMP accumulation to isopropylnoradrenaline was further augmented by re-feeding. Noradrenaline produced a significant rise in the level of cAMP and significantly stimulated the rate of glycerol production. It is concluded that the nutritional changes are of significance for the adrenergic regulation of lipolysis as indicated by the response of cAMP to the catecholamines. In pharmacological terms, fasting for one week resulted in increased alpha-as well as beta-adrenergic responsiveness. Increased basal lipolysis during fasting may be related to an increased level of cAMP or a direct activation of lipase."}
{"id": "PMID:185881", "title": "Urethane-induced hyperglycemia in rats.", "content": "The occurrence of hyperglycemia and glucosuria was investigated in urethane anesthetized rats. The substance found in urine was chromatographically identified with d-glucose. Marked increase in the arterial blood catecholamine concentration was observed. Hyperglycemia appeared after infusion of catecholamines in concentration comparable to that found in the blood of anaesthetized rats. The results support a hypothesis that the urethane-induced hyperglycemia is caused by an endogenous adrenaline liberation. Some observations in hypophysectomized and adrenalectomized rats indicate that the adrenal steroids may play a role in this reaction.", "contents": "Urethane-induced hyperglycemia in rats. The occurrence of hyperglycemia and glucosuria was investigated in urethane anesthetized rats. The substance found in urine was chromatographically identified with d-glucose. Marked increase in the arterial blood catecholamine concentration was observed. Hyperglycemia appeared after infusion of catecholamines in concentration comparable to that found in the blood of anaesthetized rats. The results support a hypothesis that the urethane-induced hyperglycemia is caused by an endogenous adrenaline liberation. Some observations in hypophysectomized and adrenalectomized rats indicate that the adrenal steroids may play a role in this reaction."}
{"id": "PMID:185887", "title": "Studies on the mechanism of PGF2alpha and gonadotropin interactions on LH receptor function in corpora lutea during luteolysis.", "content": "1. In the present experiments evidence was shown which demonstrates that PGF2alpha treatment of the rat produces a rapid fall in circulating progesterone in the latter part of pseudopregnancy but not shortly after corpus luteum formation. This refractory period of at least 3 days following ovulation is similar to that which occurs in large animals, such as the cow. 2. Loss of luteal LH receptors was associated with a loss in LH-stimulated progesterone synthesis and an attenuation of LH-stimulated cyclic AMP synthesis in vitro, a finding which supports a functional loss of LH activity in such tissues exposed in vivo to PGF2alpha. Tissue levels of cyclic GMP were generally decreased by both LH, PGF2alpha, and incubation and the relevance of the latter cyclic nucleotide remains obscure in luteolysis and corpus luteum function. 3. The depression of progesterone induced by PGF2alpha precedes a marked drop in corpus luteum LH receptors but no change in reeptor affinity was seen. For example, the first significant drop in LH receptors was observed 8 hr after PGF2alpha treatment whereas serum progesterone was depressed within 2 hr. 4. Prolactin administration to animals simultaneously with PGF2alpha blocked the loss in LH receptors and serum progesterone observed with PGF2alpha treatment alone. In one experiment, but not in the other, prolactin treatment alone produced an elevation in corpus luteum LH receptors. Suppression of endogenous prolactin secretion with ergocryptine mimicked the effect of PGF2alpha on both the LH receptor and serum progesterone and this effect was also blocked with simultaneous prolactin treatment. It is concluded that the mechanism of PGF2alpha-induced luteolysis has several components. The initial event appears to be due to direct gonadotropin antagonism which occurs independently from a change in quantity of luteal LH receptors. This effect has been shown in vitro (10) as well as in vivo (3) and the mechanism appears not to be related to changes in ovarian hemodynamics and not to direct antagonism of LH binding to its receptor (23). Possibly the early effect of PGF2alpha may be due to elevation of cGMP which then antagonizes cyclic AMP action, but our studies to date have been unsuccessful in demonstrating such a response. Eight hours following PGF2alpha administration, the first measurable decrease in LH receptors was seen and this response was correlated with the first sign of functional luteolysis, elevation of serum 20alpha-ol. The latter response is correlated with a loss of prolactin action on the corpus luteum; it was therefore interesting to observe that prolactin blocked, and ergocryptine mimicked, the PGF2alpha effect on the LH receptor and serum progesterone. Thus, one is lead to the conclusion that the mechanism of luteolysis produced by PGF2alpha in the rat is closely associated with a loss in prolactin activity...", "contents": "Studies on the mechanism of PGF2alpha and gonadotropin interactions on LH receptor function in corpora lutea during luteolysis. 1. In the present experiments evidence was shown which demonstrates that PGF2alpha treatment of the rat produces a rapid fall in circulating progesterone in the latter part of pseudopregnancy but not shortly after corpus luteum formation. This refractory period of at least 3 days following ovulation is similar to that which occurs in large animals, such as the cow. 2. Loss of luteal LH receptors was associated with a loss in LH-stimulated progesterone synthesis and an attenuation of LH-stimulated cyclic AMP synthesis in vitro, a finding which supports a functional loss of LH activity in such tissues exposed in vivo to PGF2alpha. Tissue levels of cyclic GMP were generally decreased by both LH, PGF2alpha, and incubation and the relevance of the latter cyclic nucleotide remains obscure in luteolysis and corpus luteum function. 3. The depression of progesterone induced by PGF2alpha precedes a marked drop in corpus luteum LH receptors but no change in reeptor affinity was seen. For example, the first significant drop in LH receptors was observed 8 hr after PGF2alpha treatment whereas serum progesterone was depressed within 2 hr. 4. Prolactin administration to animals simultaneously with PGF2alpha blocked the loss in LH receptors and serum progesterone observed with PGF2alpha treatment alone. In one experiment, but not in the other, prolactin treatment alone produced an elevation in corpus luteum LH receptors. Suppression of endogenous prolactin secretion with ergocryptine mimicked the effect of PGF2alpha on both the LH receptor and serum progesterone and this effect was also blocked with simultaneous prolactin treatment. It is concluded that the mechanism of PGF2alpha-induced luteolysis has several components. The initial event appears to be due to direct gonadotropin antagonism which occurs independently from a change in quantity of luteal LH receptors. This effect has been shown in vitro (10) as well as in vivo (3) and the mechanism appears not to be related to changes in ovarian hemodynamics and not to direct antagonism of LH binding to its receptor (23). Possibly the early effect of PGF2alpha may be due to elevation of cGMP which then antagonizes cyclic AMP action, but our studies to date have been unsuccessful in demonstrating such a response. Eight hours following PGF2alpha administration, the first measurable decrease in LH receptors was seen and this response was correlated with the first sign of functional luteolysis, elevation of serum 20alpha-ol. The latter response is correlated with a loss of prolactin action on the corpus luteum; it was therefore interesting to observe that prolactin blocked, and ergocryptine mimicked, the PGF2alpha effect on the LH receptor and serum progesterone. Thus, one is lead to the conclusion that the mechanism of luteolysis produced by PGF2alpha in the rat is closely associated with a loss in prolactin activity..."}
{"id": "PMID:185890", "title": "Tumors of the islets of Langerhans.", "content": "The islet cell tumors of the pancreas are now known to produce a variety of polypeptides in addition to insulin. These include glucagon, serotonin, corticotropin, melanocyte-stimulating hormone, gastrin and a secretinlike hormone that may be VIP or a combination of such polypeptides. The development and wide availability of the newer immunoassays for the various recognized hormones as well as candidate hormones of the gut will simplify the diagnosis of these challenging tumors, which up until this time have produced symptoms that were bizarre and often fatal to the patient.", "contents": "Tumors of the islets of Langerhans. The islet cell tumors of the pancreas are now known to produce a variety of polypeptides in addition to insulin. These include glucagon, serotonin, corticotropin, melanocyte-stimulating hormone, gastrin and a secretinlike hormone that may be VIP or a combination of such polypeptides. The development and wide availability of the newer immunoassays for the various recognized hormones as well as candidate hormones of the gut will simplify the diagnosis of these challenging tumors, which up until this time have produced symptoms that were bizarre and often fatal to the patient."}
{"id": "PMID:185891", "title": "The detection and diagnosis of early, occult and minimal breast cancer.", "content": "Radical mastectomy as originally conceived at the turn of the century consisted of complete removal of the breast tissue, the overlying skin, the pectoral muscles, the intervening lymphatics and the axillary lymph nodes. The aim was logical but initially the results were poor. Only 41% of the 76 patients in Halsted's original series were without disease at the end of 3 years. The principal reason for this was the advanced stage of disease in the patients selected for treatment. By contrast, Gilbertsen, using clinical examination alone, surveyed women 45 years of age or older and found that of 32 patients with breast cancers detected by the screening procedure, 24 had no axillary lymph node involvement. The absolute 5-year survival rate of this group was 96%, which approaches the anticipated survival of comparable women free of breast cancer. Those with positive lymph nodes had an absolute survival rate of 75% at 5 years. Further, of 13 patients observed for 10 years, the survival rate for those without node involvement was 90% and for patients with node involvement was 33%. Patients treated at the Barnes Hospital in St. Louis between 1912 and 1933 were contrasted with similarly treated patients at the Barnes Hospital and the Ellis Fischel Cancer Hospital from 1940 to 1955. A poorer survival rate in the earlier series was related primarily to the greater frequency of advanced and larger tumors. That a significant reduction in breast cancer mortality can be achieved is becoming increasingly apparent. Among survey-detected breast cancers in the study conducted by the Health Insurance Plan of Greater New York, the 6-year mortality was half of that of controls. This reduction is even more impressive when one considers that among these patients were many with full invasive, mass-forming carcinomas at the time of initial screening. A recent report by Wanebo, Huvos and Urban discusses the treatment of prognostically favorable forms of breast cancer by modified radical mastectomy. It is possible to select from among their patients those who fit the definition of minimal breast cancer. In this group the 5-year survival rate was 97% and the 10-year survival rate was 95%. Only 1 patient died of breast cancer in 10 years. In another reported group of 65 patients with intraductal carcinoma only, there were no deaths due to breast cancer in 10 years. Should the NCI-ACS demonstration projects show, as now seems probable, that community screening programs can be effective in early breast cnacer detection, it is to be anticipated that widespread public demand for screening facilities will follow. This may present insurmountable logistic and economic problems. The total number of radiologists in the United States is not sufficient to screen annually the total population of women over age 40, or even over age 50. There is great need for the development of criteria for the ready identification of that segment of the population in which most of the cancers would be found...", "contents": "The detection and diagnosis of early, occult and minimal breast cancer. Radical mastectomy as originally conceived at the turn of the century consisted of complete removal of the breast tissue, the overlying skin, the pectoral muscles, the intervening lymphatics and the axillary lymph nodes. The aim was logical but initially the results were poor. Only 41% of the 76 patients in Halsted's original series were without disease at the end of 3 years. The principal reason for this was the advanced stage of disease in the patients selected for treatment. By contrast, Gilbertsen, using clinical examination alone, surveyed women 45 years of age or older and found that of 32 patients with breast cancers detected by the screening procedure, 24 had no axillary lymph node involvement. The absolute 5-year survival rate of this group was 96%, which approaches the anticipated survival of comparable women free of breast cancer. Those with positive lymph nodes had an absolute survival rate of 75% at 5 years. Further, of 13 patients observed for 10 years, the survival rate for those without node involvement was 90% and for patients with node involvement was 33%. Patients treated at the Barnes Hospital in St. Louis between 1912 and 1933 were contrasted with similarly treated patients at the Barnes Hospital and the Ellis Fischel Cancer Hospital from 1940 to 1955. A poorer survival rate in the earlier series was related primarily to the greater frequency of advanced and larger tumors. That a significant reduction in breast cancer mortality can be achieved is becoming increasingly apparent. Among survey-detected breast cancers in the study conducted by the Health Insurance Plan of Greater New York, the 6-year mortality was half of that of controls. This reduction is even more impressive when one considers that among these patients were many with full invasive, mass-forming carcinomas at the time of initial screening. A recent report by Wanebo, Huvos and Urban discusses the treatment of prognostically favorable forms of breast cancer by modified radical mastectomy. It is possible to select from among their patients those who fit the definition of minimal breast cancer. In this group the 5-year survival rate was 97% and the 10-year survival rate was 95%. Only 1 patient died of breast cancer in 10 years. In another reported group of 65 patients with intraductal carcinoma only, there were no deaths due to breast cancer in 10 years. Should the NCI-ACS demonstration projects show, as now seems probable, that community screening programs can be effective in early breast cnacer detection, it is to be anticipated that widespread public demand for screening facilities will follow. This may present insurmountable logistic and economic problems. The total number of radiologists in the United States is not sufficient to screen annually the total population of women over age 40, or even over age 50. There is great need for the development of criteria for the ready identification of that segment of the population in which most of the cancers would be found..."}
{"id": "PMID:185893", "title": "His bundle recordings in a case of complete atrioventricular block combined with pre-excitation syndrome.", "content": "In  a patient with complete A-V block suffering from attacks of dizziness an intermittent A-V conduction with a short P-R interval and a delta wave of the conducted ventricular complex were observed. After accelerating the sinus rate by atropine and by exercise, one-to-one conduction was established with QRS complexes of WPW type A configuration. His bundle recordings revealed a complete block within the normal conduction system at the level of the A-V node. A slow junctional rhythm with a normal H-V interval was activating the ventricle. During atrial pacing a one-to-one conduction through an accessory pathway could be documented at cycle lengths between 800 and 380 msec. sandwiched in between zones of complete block at smaller or longer cycle lengths. During ventricular stimulation no retrograde V-A conduction could be observed. The findings support the thesis of at least two functionally different A-V pathways in patients with pre-excitation syndrome.", "contents": "His bundle recordings in a case of complete atrioventricular block combined with pre-excitation syndrome. In  a patient with complete A-V block suffering from attacks of dizziness an intermittent A-V conduction with a short P-R interval and a delta wave of the conducted ventricular complex were observed. After accelerating the sinus rate by atropine and by exercise, one-to-one conduction was established with QRS complexes of WPW type A configuration. His bundle recordings revealed a complete block within the normal conduction system at the level of the A-V node. A slow junctional rhythm with a normal H-V interval was activating the ventricle. During atrial pacing a one-to-one conduction through an accessory pathway could be documented at cycle lengths between 800 and 380 msec. sandwiched in between zones of complete block at smaller or longer cycle lengths. During ventricular stimulation no retrograde V-A conduction could be observed. The findings support the thesis of at least two functionally different A-V pathways in patients with pre-excitation syndrome."}
{"id": "PMID:185898", "title": "Effects of Rous Sarcoma Virus on the synthetic programs of chondroblasts and retinal melanoblasts.", "content": "Chondroblasts and retinal melanoblasts have been transformed with a temperature-sensitive Rous Sarcoma Virus. At permissive temperature the transformed cells do not display their unique phenotypic properties. When such transformed cells are shifted to non-permissive temperature they do display their unique phenotypic properties.", "contents": "Effects of Rous Sarcoma Virus on the synthetic programs of chondroblasts and retinal melanoblasts. Chondroblasts and retinal melanoblasts have been transformed with a temperature-sensitive Rous Sarcoma Virus. At permissive temperature the transformed cells do not display their unique phenotypic properties. When such transformed cells are shifted to non-permissive temperature they do display their unique phenotypic properties."}
{"id": "PMID:185899", "title": "An outbreak of infectious mononucleosis among the personnel of an outpatient clinic.", "content": "During a four-week period, nine current or recent primary Epstein-Barr virus (EBV) infections were identified among 29 staff members of an obstetrics and gynecology outpatient clinic of an air force base hospital by EBV-specific serologic tests; i.e., early detection of IgM antibodies to EB viral capsid antigen (VCA), high titers of IgG antibodies to VCA, presence of antibodies to the D (diffuse) component of the EBV-induced early antigen (EA) complex and initial absence and later development of antibodies to the EBV-associated nuclear antigen (EBNA). Five of these individuals showed classical signs and symptoms of infectious mononucleosis (IM) so that the ratio between overt and silent infections was 1.25:1. All but one of these nine individuals gave positive monospot reactions. Three additional staff members were reported to be monospot-positive, of whom two, with prior histories of IM, had IM-like illnesses during the study period but the results of EBV-specific serologic tests were indicative of infections in the past. The EBV infections were limited to the nurses, corpsmen and administrative personnel, of whom none remained susceptible (antibody negative). The virus did not spread to the medical staff although two of the residents had no antibodies to EBV. The data indicate that under some circumstances IM may be more contagious than usually observed.", "contents": "An outbreak of infectious mononucleosis among the personnel of an outpatient clinic. During a four-week period, nine current or recent primary Epstein-Barr virus (EBV) infections were identified among 29 staff members of an obstetrics and gynecology outpatient clinic of an air force base hospital by EBV-specific serologic tests; i.e., early detection of IgM antibodies to EB viral capsid antigen (VCA), high titers of IgG antibodies to VCA, presence of antibodies to the D (diffuse) component of the EBV-induced early antigen (EA) complex and initial absence and later development of antibodies to the EBV-associated nuclear antigen (EBNA). Five of these individuals showed classical signs and symptoms of infectious mononucleosis (IM) so that the ratio between overt and silent infections was 1.25:1. All but one of these nine individuals gave positive monospot reactions. Three additional staff members were reported to be monospot-positive, of whom two, with prior histories of IM, had IM-like illnesses during the study period but the results of EBV-specific serologic tests were indicative of infections in the past. The EBV infections were limited to the nurses, corpsmen and administrative personnel, of whom none remained susceptible (antibody negative). The virus did not spread to the medical staff although two of the residents had no antibodies to EBV. The data indicate that under some circumstances IM may be more contagious than usually observed."}
{"id": "PMID:185900", "title": "Herpesvirus hominis type 2 meningoencephalitis following renal transplantation.", "content": "Herpesvirus hominis (HVH) type 2 meningoencephalitis, confirmed by isolation of the virus from cerebrospinal fluid and brain biopsy specimens, is described in a 44 year old man following renal transplantation. An HVH type 2 genital infection developed two weeks after renal transplantation, which was followed by meningoencephalitis 10 days later. Subsequently an intracerebral hemorrhage developed with evidence of diffuse vasculitis on arteriography. In a second transplant patient a similar clinical syndrome also developed after an HVH type 2 genital infection, but viral studies were not made to confirm the etiology of the meningoencephalitis. HVH has been recognized as a cause ot mucocutaneous diseases in  recipients of renal transplants, but involvement of the central nervous system has not been reported.", "contents": "Herpesvirus hominis type 2 meningoencephalitis following renal transplantation. Herpesvirus hominis (HVH) type 2 meningoencephalitis, confirmed by isolation of the virus from cerebrospinal fluid and brain biopsy specimens, is described in a 44 year old man following renal transplantation. An HVH type 2 genital infection developed two weeks after renal transplantation, which was followed by meningoencephalitis 10 days later. Subsequently an intracerebral hemorrhage developed with evidence of diffuse vasculitis on arteriography. In a second transplant patient a similar clinical syndrome also developed after an HVH type 2 genital infection, but viral studies were not made to confirm the etiology of the meningoencephalitis. HVH has been recognized as a cause ot mucocutaneous diseases in  recipients of renal transplants, but involvement of the central nervous system has not been reported."}
{"id": "PMID:185901", "title": "Angiotensin receptors in vascular tissue.", "content": "The biologic effect of angiotensin II is triggered by its interaction with components of target organs, which specifically recognize the hormone. These receptors have been studied with the use of radioactive angiotensin and, as for other peptidic hormones, have been localized in the plasma membrane of target cells. Such angiotensin  receptors have been characterized in three target organs: vascular tissue, uterus and adrenal cortex. The binding characteristics differ in contractile tissue and in adrenal glands, the N and C terminal ends of angiotensin being involved in the former, whereas the N terminus does not appear to have the same importance in the latter. Numerous factors, including ionic composition, seem to be able to modify angiotensin-receptor interaction in vascular smooth muscle. However, the molecular mechanisms responsible for angiotensin binding and for the transmission of the signal determined by receptor-angiotensin interaction are not yet understood. As observed with other peptidic hormones, the number of angiotensin receptors seems to be susceptible to variation under certain conditions. In uterine smooth muscle, it was shown that the number of receptors increased after nephrectomy, a phenomenon which was prevented by the prolonged infusion of angiotensin. The significance of such a variation remains unknown, but it may be partially responsible for the inverse relationship that exists between the endogenous angiotensin level and the pressor effect of exogenous angiotensin. In the near future, investigation of the angiotensin-receptor mechanism will probably answer whether the variation in angiotensin receptors is similar in all target tissues and whether an angiotensin-receptor mechanism is involved in the pathogenesis of certain varieties of hypertension. In addition, a precise understanding of the angiotensin-receptor interaction with help the development of new angiotensin antagonists.", "contents": "Angiotensin receptors in vascular tissue. The biologic effect of angiotensin II is triggered by its interaction with components of target organs, which specifically recognize the hormone. These receptors have been studied with the use of radioactive angiotensin and, as for other peptidic hormones, have been localized in the plasma membrane of target cells. Such angiotensin  receptors have been characterized in three target organs: vascular tissue, uterus and adrenal cortex. The binding characteristics differ in contractile tissue and in adrenal glands, the N and C terminal ends of angiotensin being involved in the former, whereas the N terminus does not appear to have the same importance in the latter. Numerous factors, including ionic composition, seem to be able to modify angiotensin-receptor interaction in vascular smooth muscle. However, the molecular mechanisms responsible for angiotensin binding and for the transmission of the signal determined by receptor-angiotensin interaction are not yet understood. As observed with other peptidic hormones, the number of angiotensin receptors seems to be susceptible to variation under certain conditions. In uterine smooth muscle, it was shown that the number of receptors increased after nephrectomy, a phenomenon which was prevented by the prolonged infusion of angiotensin. The significance of such a variation remains unknown, but it may be partially responsible for the inverse relationship that exists between the endogenous angiotensin level and the pressor effect of exogenous angiotensin. In the near future, investigation of the angiotensin-receptor mechanism will probably answer whether the variation in angiotensin receptors is similar in all target tissues and whether an angiotensin-receptor mechanism is involved in the pathogenesis of certain varieties of hypertension. In addition, a precise understanding of the angiotensin-receptor interaction with help the development of new angiotensin antagonists."}
{"id": "PMID:185902", "title": "Vascular angiotensin receptors and their role in blood pressure control.", "content": "The renin angiotensin system has an important role in regulating arterial blood pressure in homeostasis and disease. A reciprocal relationship exists between sodium balance and the circulating levels of renin and angiotensin II. The vascular responsiveness to angiotensin II, the major vasconstrictor component of the renal pressor system, can be impaired by numerous factors including sodium depletion or a reduction in effective plasma volume. In situations in which the renin-angiotensin system is activated, a negative relationship between the angiotensin II pressor response and the circulating angiotensin II level is observed. This effect seems to involve a change of the angiotensin II receptor interaction in the vascular smooth muscle. The prevention of angiotensin II generation by the inhibition of converting enzyme causes an immediate increase in the pressor response to angiotensin; after bilateral nephrectomy, it takes much longer to develop. In addition, the depressor response to angiotensin antagnoists and converting enzyme inhibitor is preserved after bilateral nephrectomy for much longer periods than can be accounted for by the disappearance of circulating renin. These observations support the view that the decrease in vascular response to angiotensin II during sodium deprivation or when body fluid volumes are reduced is the result of prior occupancy of the receptor sites by endogenous hormone generated both in the plasma and locally within blood vessel walls. Therefore, a change in the number or affinity of receptors consequent to a change in sodium balance or as a modulating function of the renin-angiotensin system need not be postulated to explain changes in angiotensin vascular responsiveness.", "contents": "Vascular angiotensin receptors and their role in blood pressure control. The renin angiotensin system has an important role in regulating arterial blood pressure in homeostasis and disease. A reciprocal relationship exists between sodium balance and the circulating levels of renin and angiotensin II. The vascular responsiveness to angiotensin II, the major vasconstrictor component of the renal pressor system, can be impaired by numerous factors including sodium depletion or a reduction in effective plasma volume. In situations in which the renin-angiotensin system is activated, a negative relationship between the angiotensin II pressor response and the circulating angiotensin II level is observed. This effect seems to involve a change of the angiotensin II receptor interaction in the vascular smooth muscle. The prevention of angiotensin II generation by the inhibition of converting enzyme causes an immediate increase in the pressor response to angiotensin; after bilateral nephrectomy, it takes much longer to develop. In addition, the depressor response to angiotensin antagnoists and converting enzyme inhibitor is preserved after bilateral nephrectomy for much longer periods than can be accounted for by the disappearance of circulating renin. These observations support the view that the decrease in vascular response to angiotensin II during sodium deprivation or when body fluid volumes are reduced is the result of prior occupancy of the receptor sites by endogenous hormone generated both in the plasma and locally within blood vessel walls. Therefore, a change in the number or affinity of receptors consequent to a change in sodium balance or as a modulating function of the renin-angiotensin system need not be postulated to explain changes in angiotensin vascular responsiveness."}
{"id": "PMID:185903", "title": "Estimating renin participation in hypertension: superiority of converting enzyme inhibitor over saralasin.", "content": "This study was designed to examine more closely the differences in blood pressure responses in hypertensive patients to two agents which block the renin-angiotensin system. Accordingly, 39 seated patients received under the same conditions both saralasin, an octapeptide competitive antagonist of angiotensin II, and the nonapeptide converting enzyme inhibitor, SQ20881, which blocks the generation of angiotensin II from angiotensin I. A second component of the study involved administration of these agents in 10 addtional studies in anephric subjects. Although both agents produced maximal responses in blood pressure that correlated well with each other (p less than 0.001) and with the pretreatment plasma renin levels (p less than 0.001), analysis of the results by renin subgroups revealed significant differences. Thus, both drugs lowered the diastolic pressures of patients with high renin levels, but but converting enzyme inhibitor produced changes of greater amplitude (p less than 0.05). In contrast, saralasin was consistently pressor in both patients with low renin levels and anephric patients in whom converting enzyme blockade preduced no significant changes in blood pressure. Another impressive disparity in the responses to the two agents occurred in the group with normal renin levels in whom saralasin produced either neutral or pressor responses (mean change was +2.0 +/- 1.5 standard error of the mean (SEM) per cent control diastolic pressure) whereas the converting enzyme inhibitor consistently induced depressor responses (mean change was -10.2 +/- 1.2 per cent, p less than 0.001). Altogether, the results suggest that converting enzyme inhibitor tests for angiotensin II-dependent blood pressure with more sensitivity than the partial agonist saralasin. Moreover, it is unlikely that the differences between the responses to the two agents were due to bradykinin accumulation, since depressor responses to converting enzyme inhibitor were not observed in the patients with low renin levels and the anephric patients.", "contents": "Estimating renin participation in hypertension: superiority of converting enzyme inhibitor over saralasin. This study was designed to examine more closely the differences in blood pressure responses in hypertensive patients to two agents which block the renin-angiotensin system. Accordingly, 39 seated patients received under the same conditions both saralasin, an octapeptide competitive antagonist of angiotensin II, and the nonapeptide converting enzyme inhibitor, SQ20881, which blocks the generation of angiotensin II from angiotensin I. A second component of the study involved administration of these agents in 10 addtional studies in anephric subjects. Although both agents produced maximal responses in blood pressure that correlated well with each other (p less than 0.001) and with the pretreatment plasma renin levels (p less than 0.001), analysis of the results by renin subgroups revealed significant differences. Thus, both drugs lowered the diastolic pressures of patients with high renin levels, but but converting enzyme inhibitor produced changes of greater amplitude (p less than 0.05). In contrast, saralasin was consistently pressor in both patients with low renin levels and anephric patients in whom converting enzyme blockade preduced no significant changes in blood pressure. Another impressive disparity in the responses to the two agents occurred in the group with normal renin levels in whom saralasin produced either neutral or pressor responses (mean change was +2.0 +/- 1.5 standard error of the mean (SEM) per cent control diastolic pressure) whereas the converting enzyme inhibitor consistently induced depressor responses (mean change was -10.2 +/- 1.2 per cent, p less than 0.001). Altogether, the results suggest that converting enzyme inhibitor tests for angiotensin II-dependent blood pressure with more sensitivity than the partial agonist saralasin. Moreover, it is unlikely that the differences between the responses to the two agents were due to bradykinin accumulation, since depressor responses to converting enzyme inhibitor were not observed in the patients with low renin levels and the anephric patients."}
{"id": "PMID:185905", "title": "Observations on the human corpus luteum: histochemical changes during development and involution.", "content": "Morphologic studies of the developing, gestational, and involuting corpus luteum show that rapid structural changes occur and that involution is not associated with an appropriate inflammatory response. Histochemical techniques were used to demonstrate several patterns of enzyme activity. The luteunized granulosa cells stained with increasing intensity for lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, glucose-6-phosphatase, and 3 beta-hydroxysteroid dehydrogenase, but reactivity for these enzymes dropped markedly with early involution, and staining was never conspicuous in the organizing cavity. Reactions for acid phosphatase, glucosaminidase, galactosidase, glucuronidase, and nonspecific esterase were also present in the developing corpus luteum, but staining decreased more slowly during involution and was prominent in the occasional macrophages in the granulosa and the granulation tissue in the cavity. Staining was moderately intense for all of the enzymes in the corpus luteum of pregnancy. The decrease in activity for these metabolic enzymes confirms the histologic impression of degeneration, but the loss of staining for lysosomal enzymes was more rapid than expected. The latter finding complicates the hypothesis of involution of involution of the corpus luteum as an example of programmed cell death.", "contents": "Observations on the human corpus luteum: histochemical changes during development and involution. Morphologic studies of the developing, gestational, and involuting corpus luteum show that rapid structural changes occur and that involution is not associated with an appropriate inflammatory response. Histochemical techniques were used to demonstrate several patterns of enzyme activity. The luteunized granulosa cells stained with increasing intensity for lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, glucose-6-phosphatase, and 3 beta-hydroxysteroid dehydrogenase, but reactivity for these enzymes dropped markedly with early involution, and staining was never conspicuous in the organizing cavity. Reactions for acid phosphatase, glucosaminidase, galactosidase, glucuronidase, and nonspecific esterase were also present in the developing corpus luteum, but staining decreased more slowly during involution and was prominent in the occasional macrophages in the granulosa and the granulation tissue in the cavity. Staining was moderately intense for all of the enzymes in the corpus luteum of pregnancy. The decrease in activity for these metabolic enzymes confirms the histologic impression of degeneration, but the loss of staining for lysosomal enzymes was more rapid than expected. The latter finding complicates the hypothesis of involution of involution of the corpus luteum as an example of programmed cell death."}
{"id": "PMID:185907", "title": "Blood as a potential vehicle for the cytomegaloviruses.", "content": "This study analyzed transfused blood as a potential vehicle for infectious cytomegalovirus (CMV) particles. A total of 207 patients who received a total number of 897 units of blood were monitored. A complement-fixing antibody titer of 1:8, as determined by micro-titer technique, was observed in 14.8 per cent of the blood units. A total of 140 individuals in this study were serosusceptible. Eighty-six serosusceptible individuals did not receive blood containing complement-fixing CMV antibodies. In this patient population three instances of seroconversion were identified. Among the 54 serosusceptible individuals who received at least one unit of blood whose complement-fixing titer to the AD-169 strain of CMV was 1:8 or greater, 13 seroconversions were observed.", "contents": "Blood as a potential vehicle for the cytomegaloviruses. This study analyzed transfused blood as a potential vehicle for infectious cytomegalovirus (CMV) particles. A total of 207 patients who received a total number of 897 units of blood were monitored. A complement-fixing antibody titer of 1:8, as determined by micro-titer technique, was observed in 14.8 per cent of the blood units. A total of 140 individuals in this study were serosusceptible. Eighty-six serosusceptible individuals did not receive blood containing complement-fixing CMV antibodies. In this patient population three instances of seroconversion were identified. Among the 54 serosusceptible individuals who received at least one unit of blood whose complement-fixing titer to the AD-169 strain of CMV was 1:8 or greater, 13 seroconversions were observed."}
{"id": "PMID:185908", "title": "Immunologic studies in patients with trophoblastic neoplasia.", "content": "Histocompatibility antigen was analyzed in 1,104 patients with trophoblastic neoplasia and in their husbands. Furthermore, the patients were examined for cell-mediated immunity. (1) There was no significant difference in the frequency of the ABO blood groups between patients with hydatidiform or destructive mole or choriocarcinoma and healthy persons. (2) The incidence of appearance of anti-HL-A antibody was more frequent in the patients with destructive mole than in those with hydatidiform mole or choriocarcinoma. (3) Patients with choriocarcinoma were frequently incompatible at HL-A9, HL-A10, and HL-AW5. (4) The mixed lymphocyte culture (MLC) showed lower values in patients with choriocarcinoma than in those with destructive mole. Histocompatibility between the patients and their husbands was more remarkable in the patients with chriocarcinoma than in those with destructive mole. (5) In patients with choriocarcinoma, incompatibility was detected at HL-A10, HL-A11, HL-AW5, and HL-A13 in the group with good prognosis and at HL-A5, HL-AW15, and HL-A12 in the poor prognosis group. The MLC value was lower in the poor prognosis group.", "contents": "Immunologic studies in patients with trophoblastic neoplasia. Histocompatibility antigen was analyzed in 1,104 patients with trophoblastic neoplasia and in their husbands. Furthermore, the patients were examined for cell-mediated immunity. (1) There was no significant difference in the frequency of the ABO blood groups between patients with hydatidiform or destructive mole or choriocarcinoma and healthy persons. (2) The incidence of appearance of anti-HL-A antibody was more frequent in the patients with destructive mole than in those with hydatidiform mole or choriocarcinoma. (3) Patients with choriocarcinoma were frequently incompatible at HL-A9, HL-A10, and HL-AW5. (4) The mixed lymphocyte culture (MLC) showed lower values in patients with choriocarcinoma than in those with destructive mole. Histocompatibility between the patients and their husbands was more remarkable in the patients with chriocarcinoma than in those with destructive mole. (5) In patients with choriocarcinoma, incompatibility was detected at HL-A10, HL-A11, HL-AW5, and HL-A13 in the group with good prognosis and at HL-A5, HL-AW15, and HL-A12 in the poor prognosis group. The MLC value was lower in the poor prognosis group."}
{"id": "PMID:185909", "title": "Oxygen delivery in perfused rat kidney: NADH fluorescence and renal functional state.", "content": "Changes in steady-state levels of reduced pyridine nucleotide (PN) recorded by continuous monitoring of surface fluorescence were correlated with changes in physiological function of perfused rat kidneys when subjected to anoxia, ischemia, hypothermia, variations in perfusion pressure, inhibition of Na-K ATPase, and uncoupling of oxidative phosphorylation. Biphasic responses of PN reduction and oxidation during ischemic cycles at varying temperatures and anoxic cycles at different perfusion pressures demonstrated the presence of two different cell populations in the kidney cortex, those with sufficient oxygen and those without. The magnitude of PN fluorescence change during ischemia increased with decreasing temperature demonstrating better tissue oxygenation during hypothermia. The measurement of mitochondrial NADH oxidation in the perfused kidney during transitions from CO anoxia to normoxia was made possible by flash photolytic activation of mitochondrial electron transport. The half time for NADH oxidation (125 ms) was independent of the rate of oxygen delivery while the initial rate and extent of reaction was faster and steeper, respectively, at higher perfusion pressure, due to a better tissue oxygenation and faster CO washout.", "contents": "Oxygen delivery in perfused rat kidney: NADH fluorescence and renal functional state. Changes in steady-state levels of reduced pyridine nucleotide (PN) recorded by continuous monitoring of surface fluorescence were correlated with changes in physiological function of perfused rat kidneys when subjected to anoxia, ischemia, hypothermia, variations in perfusion pressure, inhibition of Na-K ATPase, and uncoupling of oxidative phosphorylation. Biphasic responses of PN reduction and oxidation during ischemic cycles at varying temperatures and anoxic cycles at different perfusion pressures demonstrated the presence of two different cell populations in the kidney cortex, those with sufficient oxygen and those without. The magnitude of PN fluorescence change during ischemia increased with decreasing temperature demonstrating better tissue oxygenation during hypothermia. The measurement of mitochondrial NADH oxidation in the perfused kidney during transitions from CO anoxia to normoxia was made possible by flash photolytic activation of mitochondrial electron transport. The half time for NADH oxidation (125 ms) was independent of the rate of oxygen delivery while the initial rate and extent of reaction was faster and steeper, respectively, at higher perfusion pressure, due to a better tissue oxygenation and faster CO washout."}
{"id": "PMID:185910", "title": "Phasic and tonic components of gustatory response in the frog.", "content": "Characteristics of phasic and tonic responses of the frog glossopharyngeal nerve to various salts were examined under a variety of conditions. The results obtained are summarized as follows: 1) The salt concentration of adapting solutions affected greatly the phasic component of the responses to NaCl, KCl, MgCl2, and CaCl2, whereas the tonic component was independent of the adapting condition. 2) Either the phasic or tonic component was preferentially suppressed under appropriate conditions. 3) An abrupt rise of temperature of stimulating solution produced a phasic response. Magnitude of the phasic response induced by a rise of temperature was a function of both species and concentration of salts in the stimulating solution. 4) Binding of Hg2+ to the receptor and elimination of the bound Hg2+ by mercaptoethanol gave similar large phasic response. A slow elimination of the bound Hg2+ led to no response. It was concluded that a phasic response appears only when environments such as salt concentration or temperature are changing and that its magnitude is related to the rate of changes, whereas a tonic response represents information of the receptor membrane in an equilibrium state. Discussion on the obtained results was made under an assumption that the phasic response is attributed to a dynamic conformational change of the receptor membrane.", "contents": "Phasic and tonic components of gustatory response in the frog. Characteristics of phasic and tonic responses of the frog glossopharyngeal nerve to various salts were examined under a variety of conditions. The results obtained are summarized as follows: 1) The salt concentration of adapting solutions affected greatly the phasic component of the responses to NaCl, KCl, MgCl2, and CaCl2, whereas the tonic component was independent of the adapting condition. 2) Either the phasic or tonic component was preferentially suppressed under appropriate conditions. 3) An abrupt rise of temperature of stimulating solution produced a phasic response. Magnitude of the phasic response induced by a rise of temperature was a function of both species and concentration of salts in the stimulating solution. 4) Binding of Hg2+ to the receptor and elimination of the bound Hg2+ by mercaptoethanol gave similar large phasic response. A slow elimination of the bound Hg2+ led to no response. It was concluded that a phasic response appears only when environments such as salt concentration or temperature are changing and that its magnitude is related to the rate of changes, whereas a tonic response represents information of the receptor membrane in an equilibrium state. Discussion on the obtained results was made under an assumption that the phasic response is attributed to a dynamic conformational change of the receptor membrane."}
{"id": "PMID:185911", "title": "Lithium administration and phosphate excretion.", "content": "The phosphaturic effect of parathyroid hormone (PTH), cyclic adenosine monophosphate (cAMP), acetazolamide (Az), and HCO3 loading was studied in normal, thyroparathyroidectomized (TPTX), and Li-treated dogs. PTH administration to normal animals markedly increased fractional excretion (F) of PO4 but had a blunted effect on FPO4 in the Li-treated animals. Cyclic AMP likewise markedly increased FPO4 in the normal animals but had a markedly blunted effect in the Li-treated animals. Az led to a significant increase in FNa, FHCO3, and FPO4 in the normal animals. In the Li-treated dogs, Az induced a significant natriuresis and bicarbonaturia but failed to increase phosphaturia. HCO3 loading in normal dogs caused a significant phosphaturia while having little effect on FPO4 in Li-treated dogs. HCO3 loading to TPTX dogs was associated with a lower FPO4 as compared to normal HCO3-loaded animals. These data suggest that Li administration not only blocks the adenyl cyclase-cAMP system in the renal cortex, but it may also interfere with a step distal to the formation of cAMP, since the phosphaturic effect of both PTH and cAMP was markedly diminished in Li-treated animals.", "contents": "Lithium administration and phosphate excretion. The phosphaturic effect of parathyroid hormone (PTH), cyclic adenosine monophosphate (cAMP), acetazolamide (Az), and HCO3 loading was studied in normal, thyroparathyroidectomized (TPTX), and Li-treated dogs. PTH administration to normal animals markedly increased fractional excretion (F) of PO4 but had a blunted effect on FPO4 in the Li-treated animals. Cyclic AMP likewise markedly increased FPO4 in the normal animals but had a markedly blunted effect in the Li-treated animals. Az led to a significant increase in FNa, FHCO3, and FPO4 in the normal animals. In the Li-treated dogs, Az induced a significant natriuresis and bicarbonaturia but failed to increase phosphaturia. HCO3 loading in normal dogs caused a significant phosphaturia while having little effect on FPO4 in Li-treated dogs. HCO3 loading to TPTX dogs was associated with a lower FPO4 as compared to normal HCO3-loaded animals. These data suggest that Li administration not only blocks the adenyl cyclase-cAMP system in the renal cortex, but it may also interfere with a step distal to the formation of cAMP, since the phosphaturic effect of both PTH and cAMP was markedly diminished in Li-treated animals."}
{"id": "PMID:185912", "title": "NAD glycohydrolase activity in hearts with acute experimental infarction.", "content": "Myocardial ischemia was produced in dogs by occluding the descending coronary artery. NAD decreased in the ischemic tissue taken 2 h after the arterial ligature, and an equivalent amount of nicotinamide was detected instead. A further breakdown occurred when fragments of ischemic and nonischemic tissue were incubated at 37 degrees C. In contrast, NAD concentration remained unchanged for as long as 60 min in incubated fragments from normal heart. When normal tissue was homogenized, an immediate hydrolysis of NAD was observed with the formation of stoichiometric amounts of nicotinamide. An excess of nicotinamide completely inhibited the NAD degradation. The NAD glycohydrolase activity assayed in vitro was similar in normal, ischemic, and nonischemic cardiac homogenates. The conclusions are that the NAD loss in the ischemic heart is due to the tissue NAD glycohydrolase activity and that the cell disorganization provoked by the occlusion of the coronary artery seems to facilitate the reaction between the substrate and the enzyme.", "contents": "NAD glycohydrolase activity in hearts with acute experimental infarction. Myocardial ischemia was produced in dogs by occluding the descending coronary artery. NAD decreased in the ischemic tissue taken 2 h after the arterial ligature, and an equivalent amount of nicotinamide was detected instead. A further breakdown occurred when fragments of ischemic and nonischemic tissue were incubated at 37 degrees C. In contrast, NAD concentration remained unchanged for as long as 60 min in incubated fragments from normal heart. When normal tissue was homogenized, an immediate hydrolysis of NAD was observed with the formation of stoichiometric amounts of nicotinamide. An excess of nicotinamide completely inhibited the NAD degradation. The NAD glycohydrolase activity assayed in vitro was similar in normal, ischemic, and nonischemic cardiac homogenates. The conclusions are that the NAD loss in the ischemic heart is due to the tissue NAD glycohydrolase activity and that the cell disorganization provoked by the occlusion of the coronary artery seems to facilitate the reaction between the substrate and the enzyme."}
{"id": "PMID:185913", "title": "Impaired urinary concentrating ability and cyclic AMP in K+-depleted rat kidney.", "content": "The possibility that an alteration of the vasopressin-dependent cyclic AMP system plays a pathogenic role in the urinary concentrating defect in K+ depletion was investigated in the rat. The antidiuretic response to vasopressin was significantly less in K+-depleted rats. In these K+-depleted rats, the increase in urinary cyclic AMP excretion in response to vasopressin was also significantly less. However, repletion of K+ for 1 wk by feeding high-K+ diets restored the ability to increase urinary cyclic AMP excretion in response to vasopressin. In the in vitro incubation of renal medullary slices, the increase in cyclic AMP concentration in response to vasopressin was also significantly less in the slices obtained from K+-depleted rats than in those obtained from control rats. These findings suggest that, in K+ depletion, there is a reversible impairment of the vasopressin-dependent cyclic AMP system in the renal medulla; this impairment may play a pathogenic role in the urinary concentrating defect in K+ depletion.", "contents": "Impaired urinary concentrating ability and cyclic AMP in K+-depleted rat kidney. The possibility that an alteration of the vasopressin-dependent cyclic AMP system plays a pathogenic role in the urinary concentrating defect in K+ depletion was investigated in the rat. The antidiuretic response to vasopressin was significantly less in K+-depleted rats. In these K+-depleted rats, the increase in urinary cyclic AMP excretion in response to vasopressin was also significantly less. However, repletion of K+ for 1 wk by feeding high-K+ diets restored the ability to increase urinary cyclic AMP excretion in response to vasopressin. In the in vitro incubation of renal medullary slices, the increase in cyclic AMP concentration in response to vasopressin was also significantly less in the slices obtained from K+-depleted rats than in those obtained from control rats. These findings suggest that, in K+ depletion, there is a reversible impairment of the vasopressin-dependent cyclic AMP system in the renal medulla; this impairment may play a pathogenic role in the urinary concentrating defect in K+ depletion."}
{"id": "PMID:185914", "title": "Response of mouse liver glycogen cycle enzymes to endotoxin treatment.", "content": "The present study was undertaken to characterize endotoxin-induced changes in carbohydrate metabolism and more specifically, to determine the contribution of glycogenolysis to the loss of liver glycogen. Female ICR mice, fasted overnight, were injected with a median lethal dose (LD50, 9 mg/kg) of endotoxin extracted from Salmonella typhimurium strain SR-11. Glycogen synthase and glycogen phosphorylase activities were measured at 0.5 and 6 h after treatment. Endotoxin treatment did not alter total glycogen synthase activity, but the amount of enzyme present in the active form was significantly lower in endotoxic mice. There was no significant increase in glycogen phosphorylase activity in endotoxin-treated mice. Glycogen phosphorylase was activated to the same extent in control and endotoxic mice by decapitation or intravenous epinephrine (25 or 1 mug/kg). The results of this study indicate no significant increase in glycogen phosphorylase activity in endotoxic mice, contraindicating enhanced glycogenolysis as a mechanism for depletion of carbohydrate following endotoxin injection. Altered activation of glycogen synthase, however, may contribute to the loss of glycogen during endotoxemia.", "contents": "Response of mouse liver glycogen cycle enzymes to endotoxin treatment. The present study was undertaken to characterize endotoxin-induced changes in carbohydrate metabolism and more specifically, to determine the contribution of glycogenolysis to the loss of liver glycogen. Female ICR mice, fasted overnight, were injected with a median lethal dose (LD50, 9 mg/kg) of endotoxin extracted from Salmonella typhimurium strain SR-11. Glycogen synthase and glycogen phosphorylase activities were measured at 0.5 and 6 h after treatment. Endotoxin treatment did not alter total glycogen synthase activity, but the amount of enzyme present in the active form was significantly lower in endotoxic mice. There was no significant increase in glycogen phosphorylase activity in endotoxin-treated mice. Glycogen phosphorylase was activated to the same extent in control and endotoxic mice by decapitation or intravenous epinephrine (25 or 1 mug/kg). The results of this study indicate no significant increase in glycogen phosphorylase activity in endotoxic mice, contraindicating enhanced glycogenolysis as a mechanism for depletion of carbohydrate following endotoxin injection. Altered activation of glycogen synthase, however, may contribute to the loss of glycogen during endotoxemia."}
{"id": "PMID:185915", "title": "Can program evaluation be saved from its enthusiasts?", "content": "Program evaluation--the use of scientific techniques to measure the value of an agency's work--has become the focus of major attention and enthusiasm in mental health service planning and administration. However, the author points out that completed program evaluation studies are few in number and provide no evidence of great impact on the operation of programs or agencies and that unrealistic enthusiasm for program evaluation can lead to unrealistic rejection when performance fails to reach promise. He concludes that program evaluation should be applied only when it can have an impact, i.e., in a limited number of carefully selected cases.", "contents": "Can program evaluation be saved from its enthusiasts? Program evaluation--the use of scientific techniques to measure the value of an agency's work--has become the focus of major attention and enthusiasm in mental health service planning and administration. However, the author points out that completed program evaluation studies are few in number and provide no evidence of great impact on the operation of programs or agencies and that unrealistic enthusiasm for program evaluation can lead to unrealistic rejection when performance fails to reach promise. He concludes that program evaluation should be applied only when it can have an impact, i.e., in a limited number of carefully selected cases."}
{"id": "PMID:185916", "title": "Trends in hospital versus community treatment of mental illness: a Texas example.", "content": "The authors present statistics from Harris County, Tex., that indicate community psychiatry is making progress toward its goals of decreasing inpatient hospitalization and increasing services to the community. At the present ratio of services, a 30%-40% increase in outpatient services could theoretically eliminate the inpatient system. The authors stress the fact that inpatient facilities are still vital and offer directives for the future roles of the hospital and of community psychiatry.", "contents": "Trends in hospital versus community treatment of mental illness: a Texas example. The authors present statistics from Harris County, Tex., that indicate community psychiatry is making progress toward its goals of decreasing inpatient hospitalization and increasing services to the community. At the present ratio of services, a 30%-40% increase in outpatient services could theoretically eliminate the inpatient system. The authors stress the fact that inpatient facilities are still vital and offer directives for the future roles of the hospital and of community psychiatry."}
{"id": "PMID:185917", "title": "Who gets supervised? An extension of patient selection inequity.", "content": "A study of 89 individual psychotherapy patients followed by 17 residents in a teaching clinic demonstrated that those presented for supervision significantly differed from the others in being younger, better educated, and better liked by residents and in having higher incomes and longer term treatment. The authors discuss the implications of these findings in relation to the inequity in service time and teaching emphasis that this selection allows.", "contents": "Who gets supervised? An extension of patient selection inequity. A study of 89 individual psychotherapy patients followed by 17 residents in a teaching clinic demonstrated that those presented for supervision significantly differed from the others in being younger, better educated, and better liked by residents and in having higher incomes and longer term treatment. The authors discuss the implications of these findings in relation to the inequity in service time and teaching emphasis that this selection allows."}
{"id": "PMID:185919", "title": "Self-reports versus sleep laboratory findings in 122 drug-free subjects with complaints of chronic insomnia.", "content": "The authors compared the sleep laboratory recordings of 122 drug-free subjects who complained of chronic insomnia with the subjects' estimates of their habitual sleep characteristics and their estimated sleep time on the morning after sleeping in the laboratory. Most subjects consistently underestimated the amount of time they slept and overestimated the amount of time it took them to get to sleep in comparison with laboratory data. All subjects consistently underestimated the number of arousals they experienced. The authors discuss the implications of these findings for the treatment and definition of insomnia and for further research.", "contents": "Self-reports versus sleep laboratory findings in 122 drug-free subjects with complaints of chronic insomnia. The authors compared the sleep laboratory recordings of 122 drug-free subjects who complained of chronic insomnia with the subjects' estimates of their habitual sleep characteristics and their estimated sleep time on the morning after sleeping in the laboratory. Most subjects consistently underestimated the amount of time they slept and overestimated the amount of time it took them to get to sleep in comparison with laboratory data. All subjects consistently underestimated the number of arousals they experienced. The authors discuss the implications of these findings for the treatment and definition of insomnia and for further research."}
{"id": "PMID:185923", "title": "[Light and electron microscopic and histochemical studies on the cloaca epithelium of the domestic hen].", "content": "The mucous membrane of the Cloaca was investigated light and electronmicroscopically in 20 hens. Some histochemical investigations and a reabsorption test were carried out. The surface of the Coprodaeum is being formed by villi and deep crypts. The former disappears gradually within the Urodaeum. The latter crypts can be found down to the Proctodaeum. The epithelium of the Coprodaeum and Urodaeum consists of goblet cells and highprismatic cells containing secretory granules. The Proctodaeum can be subdivided into three parts. A cranial, containing the same epithelium as the Coprodaeum, a middle with a two layered highprismatic epithelium and a caudal part with a multilayered squamours epithelium. The columnar cells of all parts of the cloaca show a strong reaction to acid phosphatase and ATPase, whereas alkaline phosphatase is almost negative.", "contents": "[Light and electron microscopic and histochemical studies on the cloaca epithelium of the domestic hen]. The mucous membrane of the Cloaca was investigated light and electronmicroscopically in 20 hens. Some histochemical investigations and a reabsorption test were carried out. The surface of the Coprodaeum is being formed by villi and deep crypts. The former disappears gradually within the Urodaeum. The latter crypts can be found down to the Proctodaeum. The epithelium of the Coprodaeum and Urodaeum consists of goblet cells and highprismatic cells containing secretory granules. The Proctodaeum can be subdivided into three parts. A cranial, containing the same epithelium as the Coprodaeum, a middle with a two layered highprismatic epithelium and a caudal part with a multilayered squamours epithelium. The columnar cells of all parts of the cloaca show a strong reaction to acid phosphatase and ATPase, whereas alkaline phosphatase is almost negative."}
{"id": "PMID:185924", "title": "Histomorphological and histochemical studies on the preen gland of cortisone-treated male pigeons.", "content": "Intramuscular administration of cortisone acetate (5 mg daily to each for 15 days) to adult male pigeons provoked hypertrophy of the preen gland. Desquamation and loss of alveolar differentiated cells were also accelerated to a great extent. Significant changes observed in the histochemical composition of the alveoli of the preen gland of cortisone-treated pigeons were: (a) a greater accumulation of sudanophilic lipids within the alveoli, (b) an increase in the content of acidic lipids, (c) a decrease in the activity of acid phosphatase, and (d) an overall augmentation of the reaction for alkaline phosphatase. There was, however, no gross change in the activities of nonspecific esterases and lipase. The probable significance of the cortisone-induced glandular hypertrophy and histochemical changes has been briefly discussed.", "contents": "Histomorphological and histochemical studies on the preen gland of cortisone-treated male pigeons. Intramuscular administration of cortisone acetate (5 mg daily to each for 15 days) to adult male pigeons provoked hypertrophy of the preen gland. Desquamation and loss of alveolar differentiated cells were also accelerated to a great extent. Significant changes observed in the histochemical composition of the alveoli of the preen gland of cortisone-treated pigeons were: (a) a greater accumulation of sudanophilic lipids within the alveoli, (b) an increase in the content of acidic lipids, (c) a decrease in the activity of acid phosphatase, and (d) an overall augmentation of the reaction for alkaline phosphatase. There was, however, no gross change in the activities of nonspecific esterases and lipase. The probable significance of the cortisone-induced glandular hypertrophy and histochemical changes has been briefly discussed."}
{"id": "PMID:185925", "title": "Azathioprine: effects on neuromuscular transmission.", "content": "The neuromuscular effects of azathioprine were examined in the in-vivo cat soleus muscle preparation. In concentrations ranging from 10 to 1,000 mug/kg, administered intra-arterially, the agent caused motor axons to fire repetitively and produced a dose-related increase in the force of contraction. The drug reversed neuromuscular blockage produced by d-tubocurarine and potentiated the neuromuscular blockade produced by succinylcholine. The effects of theophylline, a phosphodiesterase inhibitor, on neuromuscular transmission were identical to those produced by azathioprine. Using an in-vitro assay preparation, azathioprine was found to produce 50 per cent inhibition (IC50) of phosphodiesterase at a concentration of 2 X 10(-5) M. In the same preparation, theophylline had an IC50 of 1 X 10(-4) M. Neither agent in concentrations to 10(-2) M affected cholinesterase activity measured in vitro. It is concluded that the effects of azathioprine on neuromuscular transmission are due to inhibition of phosphodiesterase in the motor nerve terminal.", "contents": "Azathioprine: effects on neuromuscular transmission. The neuromuscular effects of azathioprine were examined in the in-vivo cat soleus muscle preparation. In concentrations ranging from 10 to 1,000 mug/kg, administered intra-arterially, the agent caused motor axons to fire repetitively and produced a dose-related increase in the force of contraction. The drug reversed neuromuscular blockage produced by d-tubocurarine and potentiated the neuromuscular blockade produced by succinylcholine. The effects of theophylline, a phosphodiesterase inhibitor, on neuromuscular transmission were identical to those produced by azathioprine. Using an in-vitro assay preparation, azathioprine was found to produce 50 per cent inhibition (IC50) of phosphodiesterase at a concentration of 2 X 10(-5) M. In the same preparation, theophylline had an IC50 of 1 X 10(-4) M. Neither agent in concentrations to 10(-2) M affected cholinesterase activity measured in vitro. It is concluded that the effects of azathioprine on neuromuscular transmission are due to inhibition of phosphodiesterase in the motor nerve terminal."}
{"id": "PMID:185926", "title": "Pancreatic islet cell carcinoma in a dog treated with streptozotocin.", "content": "After surgical removal of the primary tumor and recurrence of hypoglycemia, a dog with metastatic pancreatic islet cell carcinoma was treated with streptozotocin. Nephrotoxicosis resulted after a single administration of streptozotocin.", "contents": "Pancreatic islet cell carcinoma in a dog treated with streptozotocin. After surgical removal of the primary tumor and recurrence of hypoglycemia, a dog with metastatic pancreatic islet cell carcinoma was treated with streptozotocin. Nephrotoxicosis resulted after a single administration of streptozotocin."}
{"id": "PMID:185927", "title": "Susceptibility of a new fetal pig kidney cell line (MVPK-1) to foot-and-mouth disease virus.", "content": "The Mengeling-Vaughn Porcine Kidney (MVPK-1) cell line, derived in October, 1970, from fetal pig kidneys, is susceptible to all 7 types of foot-and-mouth disease (FMD) virus. A plaque assay was developed for FMD virus that depended on washing MVPK-1 cells in serum-free medium before infection and excluding serum from 0.6% gum tragacanth overlay during plaque formation. The numbers of plaques that formed on MVPK-1 cells by a representative strain of each FMD type were comparable with the numbers of those on primary bovine calf kidney (BK) cells. Virus passaged in BK cell cultures did not have to be adapted to the cell line to obtain these results. The cell line lost susceptibility rapidly at 37 C after confluency was reached but retained susceptibility if maintained at room temperature. The cell line has the potential of replacing BK cells for many diverse purposes.", "contents": "Susceptibility of a new fetal pig kidney cell line (MVPK-1) to foot-and-mouth disease virus. The Mengeling-Vaughn Porcine Kidney (MVPK-1) cell line, derived in October, 1970, from fetal pig kidneys, is susceptible to all 7 types of foot-and-mouth disease (FMD) virus. A plaque assay was developed for FMD virus that depended on washing MVPK-1 cells in serum-free medium before infection and excluding serum from 0.6% gum tragacanth overlay during plaque formation. The numbers of plaques that formed on MVPK-1 cells by a representative strain of each FMD type were comparable with the numbers of those on primary bovine calf kidney (BK) cells. Virus passaged in BK cell cultures did not have to be adapted to the cell line to obtain these results. The cell line lost susceptibility rapidly at 37 C after confluency was reached but retained susceptibility if maintained at room temperature. The cell line has the potential of replacing BK cells for many diverse purposes."}
{"id": "PMID:185928", "title": "A canine parainfluenza viral vaccine: immunogenicity and safety.", "content": "A canine parainfluenza viral vaccine was developed and shown to be safe by absence of clinical disease in vaccinated dogs and by inability to isolate vaccine virus from blood or nasopharyngeal swabs. Backpassage in susceptible dogs, using blood of vaccinated dogs, could not be demonstrated. The vaccine produced neutralizing antibody when administered either intramuscularly or subcutaneously; however, a significantly higher immune response was obtained by intramuscular inoculation. Differences in the antibody response were not produced by tenfold dilutions of vaccine virus ranging from 10(2.9) to 10(5.9) median tissue culture infective doses. The presence of neutralizing antibody was associated significantly with decreased respiratory shedding period of challenge virus by vaccinated dogs compared to seronegative control dogs. Six days after aerosol exposure to virulent challenge virus, 100% of the controls (n = 5) but only 15% of the vaccinated dogs (n = 3) shed virus. Seven days after challenge exposure, virus could not be recovered from the vaccinated dogs, but 80% of the control dogs shed virus. An anamnestic response occurred in vaccinated dogs but not in the seronegative control dogs following challenge exposure. A mild clinical disease was produced in 3 of the 5 seronegative control dogs but not in the 20 vaccinated dogs.", "contents": "A canine parainfluenza viral vaccine: immunogenicity and safety. A canine parainfluenza viral vaccine was developed and shown to be safe by absence of clinical disease in vaccinated dogs and by inability to isolate vaccine virus from blood or nasopharyngeal swabs. Backpassage in susceptible dogs, using blood of vaccinated dogs, could not be demonstrated. The vaccine produced neutralizing antibody when administered either intramuscularly or subcutaneously; however, a significantly higher immune response was obtained by intramuscular inoculation. Differences in the antibody response were not produced by tenfold dilutions of vaccine virus ranging from 10(2.9) to 10(5.9) median tissue culture infective doses. The presence of neutralizing antibody was associated significantly with decreased respiratory shedding period of challenge virus by vaccinated dogs compared to seronegative control dogs. Six days after aerosol exposure to virulent challenge virus, 100% of the controls (n = 5) but only 15% of the vaccinated dogs (n = 3) shed virus. Seven days after challenge exposure, virus could not be recovered from the vaccinated dogs, but 80% of the control dogs shed virus. An anamnestic response occurred in vaccinated dogs but not in the seronegative control dogs following challenge exposure. A mild clinical disease was produced in 3 of the 5 seronegative control dogs but not in the 20 vaccinated dogs."}
{"id": "PMID:185929", "title": "Plaque neutralization of bluetongue virus and epizootic hemorrhagic disease virus in BHK21 cells.", "content": "Plaque assay and plaque neutralization of blue-tongue virus and epizootic hemorrhagic disease virus were studied in baby hamster kidney (BHK21) cells grown under an overlay containing gum tragacanth. Tests were done in plastic panels, each with 24 wells, and variables were established for achieving reproducible results. Four serotypes of bluetongue virus were compared, and their antigenic differences were confirmed with this new plaque-neutralization test.", "contents": "Plaque neutralization of bluetongue virus and epizootic hemorrhagic disease virus in BHK21 cells. Plaque assay and plaque neutralization of blue-tongue virus and epizootic hemorrhagic disease virus were studied in baby hamster kidney (BHK21) cells grown under an overlay containing gum tragacanth. Tests were done in plastic panels, each with 24 wells, and variables were established for achieving reproducible results. Four serotypes of bluetongue virus were compared, and their antigenic differences were confirmed with this new plaque-neutralization test."}
{"id": "PMID:185930", "title": "Sarcoma of the breast.", "content": "The records of seven patients with primary sarcoma of the breast were reviewed. The clinical course, gross and microscopic pathologic aspects as well as the optimal treatment of primary breast sarcoma are discussed. During the same period, 800 patients with carcinoma of the breast were seen.", "contents": "Sarcoma of the breast. The records of seven patients with primary sarcoma of the breast were reviewed. The clinical course, gross and microscopic pathologic aspects as well as the optimal treatment of primary breast sarcoma are discussed. During the same period, 800 patients with carcinoma of the breast were seen."}
{"id": "PMID:185934", "title": "Reovirus-like agent (rotavirus) associated with neonatal calf gastroenteritis in France.", "content": "A reo-like virus (calf rotavirus) was shown to be associated with cases of neonatal calf diarrhea in France. The virus could be detected in more than 50 p. 100 of diarrheic fecal samples, while it was practically absent in control samples originating from healthy calves that had never had diarrhea. The results obtained by electron microscopy and immunofluorescent studies indicate that the virus is closely related or identical to the agent isolated originally in the United States.", "contents": "Reovirus-like agent (rotavirus) associated with neonatal calf gastroenteritis in France. A reo-like virus (calf rotavirus) was shown to be associated with cases of neonatal calf diarrhea in France. The virus could be detected in more than 50 p. 100 of diarrheic fecal samples, while it was practically absent in control samples originating from healthy calves that had never had diarrhea. The results obtained by electron microscopy and immunofluorescent studies indicate that the virus is closely related or identical to the agent isolated originally in the United States."}
{"id": "PMID:185935", "title": "[Experimental data on the remanence of the virus causing the infectious pancreatic necrosis in Salmonidae in water environment (author's transl)].", "content": "To study the virus persistence in water environment, a purified suspension of the infectious pancreatic necrosis virus was submitted to different conditions of conservation: temperature of 4 degrees C and 1.4 degrees C in a mineral water of mean mineralization, temperature of 4 degrees C in a river water with a higher minerlization, filtered or not, with or without mud and vegetation. The cyto-infectious power of the virus subsists at least during 300 days at + 4 degrees C and 60 days at + 14 degrees C in the less mineralized water (fig I). Comparatively the virus strength sinks more slowly at 4 degrees C in the more mineralized river water (figure 2). When filtered this same river water keeps its infectious power better than its untreated homologous (fig. 3). The sediment and vegetation suspended in river water catch the virus (fig. 4 and 5).", "contents": "[Experimental data on the remanence of the virus causing the infectious pancreatic necrosis in Salmonidae in water environment (author's transl)]. To study the virus persistence in water environment, a purified suspension of the infectious pancreatic necrosis virus was submitted to different conditions of conservation: temperature of 4 degrees C and 1.4 degrees C in a mineral water of mean mineralization, temperature of 4 degrees C in a river water with a higher minerlization, filtered or not, with or without mud and vegetation. The cyto-infectious power of the virus subsists at least during 300 days at + 4 degrees C and 60 days at + 14 degrees C in the less mineralized water (fig I). Comparatively the virus strength sinks more slowly at 4 degrees C in the more mineralized river water (figure 2). When filtered this same river water keeps its infectious power better than its untreated homologous (fig. 3). The sediment and vegetation suspended in river water catch the virus (fig. 4 and 5)."}
{"id": "PMID:185936", "title": "[Increasine in the rate of cell hybridization by the cytotoxic action of strophanthin (ouabain)].", "content": "Incorporation of ouabain (G-strophantin) in the culture medium 24 h after that of Sandai virus, at a final concentration of 2.10(-6)M/1, increases considerably the yield of man/mouse or primate/mouse cellular hybridization.", "contents": "[Increasine in the rate of cell hybridization by the cytotoxic action of strophanthin (ouabain)]. Incorporation of ouabain (G-strophantin) in the culture medium 24 h after that of Sandai virus, at a final concentration of 2.10(-6)M/1, increases considerably the yield of man/mouse or primate/mouse cellular hybridization."}
{"id": "PMID:185937", "title": "Polymorphism of erythrocyte and serum enzyme systems in the Gagu of the Ivory Coast.", "content": "Erythrocyte and serum enzyme system in the Gagu of the Ivory Coast have been investigated. Some systems (e.g. PGM) differ little between the subdivisions of the Gagu group, but others differ considerably (e.g. G6PD variants). In general the red cell enzyme frequencies fall within the range of variation characteristic of African populations. Serum cholinesterase variants are present only at low frequency, and the distribution of alkaline phosphatase phenotype shows the expected correlation with ABO blood groups.", "contents": "Polymorphism of erythrocyte and serum enzyme systems in the Gagu of the Ivory Coast. Erythrocyte and serum enzyme system in the Gagu of the Ivory Coast have been investigated. Some systems (e.g. PGM) differ little between the subdivisions of the Gagu group, but others differ considerably (e.g. G6PD variants). In general the red cell enzyme frequencies fall within the range of variation characteristic of African populations. Serum cholinesterase variants are present only at low frequency, and the distribution of alkaline phosphatase phenotype shows the expected correlation with ABO blood groups."}
{"id": "PMID:185938", "title": "Tumour-associated water soluble antigen(s) in human glioblastoma demonstrated by immunodiffusion and immunoelectrophoresis.", "content": "A rabbit antiserum to human glioblastoma is tested against extracts from normal adult human organs and brain tumors. By agarose-gel immunodiffusion it is established that along with glioblastoma extract this antiserum reacts also against extracts from human kidney, lung, liver, spleen, testis and normal brain. After complete absorption with lyophilized pooled human blood plasma and consequently with extracts from normal organs (including normal brain) it continues to react with the glioblastoma extract only. This completely absorbed anti-glioblastoma antiserum gives one precipitation line with an extract from the brain of 8-10 week human embryo but does not react with extracts from other embryonic organs. It is also shown by immuno-electrophoresis  that the glioblastoma-associated antigen has a beta-globulin mobility which distinguishes it from the embryonic brain antigen.", "contents": "Tumour-associated water soluble antigen(s) in human glioblastoma demonstrated by immunodiffusion and immunoelectrophoresis. A rabbit antiserum to human glioblastoma is tested against extracts from normal adult human organs and brain tumors. By agarose-gel immunodiffusion it is established that along with glioblastoma extract this antiserum reacts also against extracts from human kidney, lung, liver, spleen, testis and normal brain. After complete absorption with lyophilized pooled human blood plasma and consequently with extracts from normal organs (including normal brain) it continues to react with the glioblastoma extract only. This completely absorbed anti-glioblastoma antiserum gives one precipitation line with an extract from the brain of 8-10 week human embryo but does not react with extracts from other embryonic organs. It is also shown by immuno-electrophoresis  that the glioblastoma-associated antigen has a beta-globulin mobility which distinguishes it from the embryonic brain antigen."}
{"id": "PMID:185944", "title": "Antiviral action and cellular toxicity of four thymidine analogues: 5-ethyl-,5-vinyl-, 5-propyl-, and 5-allyl-2'- deoxyuridine.", "content": "5-Ethyl-, 5-vinyl-, 5-propyl-, and 5-allyl-2'-deoxyuridine (dUrd) had antiviral activity against herpes simplex type 1 and type 2 grown in HeLa TK(-) cells, in the order 5-vinyl-dUrd, 5-ethyl-dUrd, 5-propyl-dUrd, 5-allyl-dUrd, but they were inactive against a TK(-) mutant of herpes simplex type 1. The antiviral activity of these compounds could be partially reversed by thymidine. Except for 5-vinyl-dUrd, they were not toxic to WI-38 and HeLa TK(-) cells at a concentration of 25 muM. All four analogues inhibited the growth of herpes simplex type 1-transformed HeLa TK(-) cells at a concentration of 1 muM.", "contents": "Antiviral action and cellular toxicity of four thymidine analogues: 5-ethyl-,5-vinyl-, 5-propyl-, and 5-allyl-2'- deoxyuridine. 5-Ethyl-, 5-vinyl-, 5-propyl-, and 5-allyl-2'-deoxyuridine (dUrd) had antiviral activity against herpes simplex type 1 and type 2 grown in HeLa TK(-) cells, in the order 5-vinyl-dUrd, 5-ethyl-dUrd, 5-propyl-dUrd, 5-allyl-dUrd, but they were inactive against a TK(-) mutant of herpes simplex type 1. The antiviral activity of these compounds could be partially reversed by thymidine. Except for 5-vinyl-dUrd, they were not toxic to WI-38 and HeLa TK(-) cells at a concentration of 25 muM. All four analogues inhibited the growth of herpes simplex type 1-transformed HeLa TK(-) cells at a concentration of 1 muM."}
{"id": "PMID:185945", "title": "Antiviral effect of pyran against systemic infection of mice with herpes simplex virus type 2.", "content": "The immunomodulator pyran markedly protected 5-week-old mice from lethal intravenous infection with herpes simplex virus type 2. The 50% lethal dose was increased almost 100-fold in pyran-treated mice as compared with controls. Although the protection was not as marked in older mice (10 and 16 weeks old), there was a significant increase in mean survival time. When the pathogenesis of herpesvirus disease was monitored in control and drug-treated mice, the effect of pyran was most evident in the spinal cord, where virus was recovered from 20 of 25 control mice and from only 6 of 25 pyran-treated mice. There was also a significant reduction in the titer of virus present, and virus appeared later in the spinal cord of pyran-treated mice than in control mice. The protective effect of pyran was observed only when the drug was administered 24 h before viral challenge, was seen after both intraperitoneal and intravenous injection, and was not due to direct inactivation of the virus.", "contents": "Antiviral effect of pyran against systemic infection of mice with herpes simplex virus type 2. The immunomodulator pyran markedly protected 5-week-old mice from lethal intravenous infection with herpes simplex virus type 2. The 50% lethal dose was increased almost 100-fold in pyran-treated mice as compared with controls. Although the protection was not as marked in older mice (10 and 16 weeks old), there was a significant increase in mean survival time. When the pathogenesis of herpesvirus disease was monitored in control and drug-treated mice, the effect of pyran was most evident in the spinal cord, where virus was recovered from 20 of 25 control mice and from only 6 of 25 pyran-treated mice. There was also a significant reduction in the titer of virus present, and virus appeared later in the spinal cord of pyran-treated mice than in control mice. The protective effect of pyran was observed only when the drug was administered 24 h before viral challenge, was seen after both intraperitoneal and intravenous injection, and was not due to direct inactivation of the virus."}
{"id": "PMID:185946", "title": "Specific inactivation of herpes simplex virus by silver nitrate at low concentrations and biological activities of the inactivated virus.", "content": "The infectivities of herpes simplex virus types 1 and 2 were inactivated by silver nitrate at concentrations of 30 muM or less, which did not affect at all the infectivities of hemagglutinating virus of Japan, vesicular stomatitis virus, poliovirus, vaccinia virus, and adenovirus. The inactivated virus retained the capability of adsorbing to the cell, with an adsorption kinetics quite similar to that of intact virus, and of inducing the concanavalin A agglutinability in the infected cells, whereas it lost completely the capability of producing viral antigens and other cytopathic changes.", "contents": "Specific inactivation of herpes simplex virus by silver nitrate at low concentrations and biological activities of the inactivated virus. The infectivities of herpes simplex virus types 1 and 2 were inactivated by silver nitrate at concentrations of 30 muM or less, which did not affect at all the infectivities of hemagglutinating virus of Japan, vesicular stomatitis virus, poliovirus, vaccinia virus, and adenovirus. The inactivated virus retained the capability of adsorbing to the cell, with an adsorption kinetics quite similar to that of intact virus, and of inducing the concanavalin A agglutinability in the infected cells, whereas it lost completely the capability of producing viral antigens and other cytopathic changes."}
{"id": "PMID:185947", "title": "Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in the presence of an adenosine deaminase inhibitor.", "content": "The antiviral activity of the fraudulent nucleoside arabinosyladenine (ara-A) against herpes simplex virus (HSV) type 1 was increased nearly 20-fold by the adenosine deaminase inhibitor, coformycin. The combination of ara-A plus coformycin was 90 times more potent in blocking HSV replication than was arabinosylhypoxanthine (ara-H). In suspension culture both drugs were more active than they were in monolayer culture. Deoxyribonucleic acid (DNA) synthesis also was inhibited by the nucleosides. Depending upon the species of DNA examined, ara-A was 8 to 15 times more active in the presence of coformycin, and the combination was 35 to 70 times more potent than ara-H. Both drugs inhibited total DNA synthesis to the same extent in uninfected and HSV-infected KB cells. In contrast, viral DNA synthesis was three to six times more susceptible to inhibition than was cellular DNA synthesis. Inhibition of viral DNA synthesis was more pronounced in suspension culture than in monolayer culture. However, the method of cell propagation did not alter the degree to which the drugs inhibited DNA synthesis in uninfected KB cells. An index has been derived to quantitate the extent of the selective inhibition of viral or cellular DNA synthesis. Fifty percent inhibitory concentrations of a drug were calculated for uninfected KB DNA synthesis and viral DNA synthesis and expressed as a ratio. The logarithm of this ratio was termed the selective index and was positive if viral DNA synthesis was inhibited preferentially or negative if uninfected KB DNA synthesis was more strongly inhibited. Data from experiments performed in monolayer culture gave positive selective index values of 0.3, 0.5, and 0.4 for ara-A plus coformycin, ara-A, and ara-H, respectively. Values of 0.7 and 0.6 were obtained from suspension culture data for ara-A plus coformycin and ara-H, respectively. Considered collectively, the data presented in this communication establish that coformycin increased the potency of ara-A but did not increase its selectivity.", "contents": "Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in the presence of an adenosine deaminase inhibitor. The antiviral activity of the fraudulent nucleoside arabinosyladenine (ara-A) against herpes simplex virus (HSV) type 1 was increased nearly 20-fold by the adenosine deaminase inhibitor, coformycin. The combination of ara-A plus coformycin was 90 times more potent in blocking HSV replication than was arabinosylhypoxanthine (ara-H). In suspension culture both drugs were more active than they were in monolayer culture. Deoxyribonucleic acid (DNA) synthesis also was inhibited by the nucleosides. Depending upon the species of DNA examined, ara-A was 8 to 15 times more active in the presence of coformycin, and the combination was 35 to 70 times more potent than ara-H. Both drugs inhibited total DNA synthesis to the same extent in uninfected and HSV-infected KB cells. In contrast, viral DNA synthesis was three to six times more susceptible to inhibition than was cellular DNA synthesis. Inhibition of viral DNA synthesis was more pronounced in suspension culture than in monolayer culture. However, the method of cell propagation did not alter the degree to which the drugs inhibited DNA synthesis in uninfected KB cells. An index has been derived to quantitate the extent of the selective inhibition of viral or cellular DNA synthesis. Fifty percent inhibitory concentrations of a drug were calculated for uninfected KB DNA synthesis and viral DNA synthesis and expressed as a ratio. The logarithm of this ratio was termed the selective index and was positive if viral DNA synthesis was inhibited preferentially or negative if uninfected KB DNA synthesis was more strongly inhibited. Data from experiments performed in monolayer culture gave positive selective index values of 0.3, 0.5, and 0.4 for ara-A plus coformycin, ara-A, and ara-H, respectively. Values of 0.7 and 0.6 were obtained from suspension culture data for ara-A plus coformycin and ara-H, respectively. Considered collectively, the data presented in this communication establish that coformycin increased the potency of ara-A but did not increase its selectivity."}
{"id": "PMID:185948", "title": "Photoinactivation of latent herpes simplex virus in rabbit kidney cells.", "content": "The photoinactivation of actively and nonactively growing herpes simplex virus by neutral red and proflavine was studied in rabbit kidney cells. Active virus growth was inhibited by both dyes under conditions which did not destroy the cells. Neutral red caused a much greater inhibition than proflavine. Neutral red also caused a reduction in the reactivation rate of latent virus when the infected cells were treated during the latent period. In the treated cultures that did reactivate virus, the average length of the latent period was increased over the control value. Proflavine treatment did not reduce the rate of reactivation of latent virus and did not increase the average latent period of the treated cultures.", "contents": "Photoinactivation of latent herpes simplex virus in rabbit kidney cells. The photoinactivation of actively and nonactively growing herpes simplex virus by neutral red and proflavine was studied in rabbit kidney cells. Active virus growth was inhibited by both dyes under conditions which did not destroy the cells. Neutral red caused a much greater inhibition than proflavine. Neutral red also caused a reduction in the reactivation rate of latent virus when the infected cells were treated during the latent period. In the treated cultures that did reactivate virus, the average length of the latent period was increased over the control value. Proflavine treatment did not reduce the rate of reactivation of latent virus and did not increase the average latent period of the treated cultures."}
{"id": "PMID:185949", "title": "Hydroxyquinolines inhibit ribonucleic acid-dependent deoxyribonucleic acid polymerase and inactivate Rous sarcoma virus and herpes simplex virus.", "content": "8-Hydroxyquinoline and several of its derivatives inactivate the transforming ability of Rous sarcoma virus and inhibit its ribonucleic acid-dependent deoxyribonucleic acid polymerase activity. The copper complex of these metal-binding ligands is as active as the free ligand. The activity of the 8-hydroxyquinolines is approximately 50-fold more effective than another group of metal-binding compounds that we have tested, the thiosemicarbazones. In contrast to the potency of the 8-hydroxyquinolines to inactivate Rous sarcoma virus, no intracellular inhibition of transformation could be demonstrated at a concentration that did not affect the growth and appearance of the cells. Cellular deoxyribonucleic acid synthesis was inhibited to a greater extent than was ribonucleic acid or protein synthesis. The phenomenon of \"concentration quenching\" was observed with high concentrations of drug, causing less inhibition of deoxyribonucleic acid synthesis than was observed with lower concentrations. Herpes simplex virus type 1 was inactivated also by the 8-hydroxyquinolines and their copper complexes. No intracellular inhibition of plaque formation was observed. Treatment with 8-hydroxyquinoline sulfate had no effect on the resolution of herpetic keratitis in rabbits. Some 8-hydroxyquinolines bind to deoxyribonucleic acid in the presence of copper, a phenomenon that may be important in their antiviral activity.", "contents": "Hydroxyquinolines inhibit ribonucleic acid-dependent deoxyribonucleic acid polymerase and inactivate Rous sarcoma virus and herpes simplex virus. 8-Hydroxyquinoline and several of its derivatives inactivate the transforming ability of Rous sarcoma virus and inhibit its ribonucleic acid-dependent deoxyribonucleic acid polymerase activity. The copper complex of these metal-binding ligands is as active as the free ligand. The activity of the 8-hydroxyquinolines is approximately 50-fold more effective than another group of metal-binding compounds that we have tested, the thiosemicarbazones. In contrast to the potency of the 8-hydroxyquinolines to inactivate Rous sarcoma virus, no intracellular inhibition of transformation could be demonstrated at a concentration that did not affect the growth and appearance of the cells. Cellular deoxyribonucleic acid synthesis was inhibited to a greater extent than was ribonucleic acid or protein synthesis. The phenomenon of \"concentration quenching\" was observed with high concentrations of drug, causing less inhibition of deoxyribonucleic acid synthesis than was observed with lower concentrations. Herpes simplex virus type 1 was inactivated also by the 8-hydroxyquinolines and their copper complexes. No intracellular inhibition of plaque formation was observed. Treatment with 8-hydroxyquinoline sulfate had no effect on the resolution of herpetic keratitis in rabbits. Some 8-hydroxyquinolines bind to deoxyribonucleic acid in the presence of copper, a phenomenon that may be important in their antiviral activity."}
{"id": "PMID:185950", "title": "Treatment of murine coccidioidomycosis with polymyxin B.", "content": "An agar dilution method was employed to test the susceptibility of 12 strains of Coccidioides immitis to polymyxin B (PB). After 3 days of incubation, eight strains were markedly inhibited by 5.0 mug of PB per ml and four strains did not grow. PB at 10 mug/ml inhibited the growth of all strains through 20 days of incubation. To determine whether PB has anticoccidioidal activity in vivo, mice in groups of 30 were infected intraperitoneally with a mean lethal dose (LD(50)) or 20 LD(50) of arthrospores of C. immitis ATCC 28868 (Silveira). Treatment by intraperitoneal injection of PB (2.5 mg/kg) was begun 2 or 5 days after challenge. By 40 days after infection, 47 and 7% of the untreated mice challenged with an LD(50), respectively, were alive. Of mice infected with an LD(50) or 20 LD(50) and treated with PB beginning 2 days after the challenge, 90% of each group were alive by day 40. Initiation of PB therapy 5 days after infection permitted survival of 84% of the mice infected with an LD(50); however, only 27% of the mice infected with 20 LD(50) survived by day 40. In this latter group there was evidence that PB prolonged life since 56% of the treated mice were alive by day 15 as compared with 30% of the controls. PB in vivo was fungistatic since the majority of treated mice had C. immitis in the liver, lungs, and spleen.", "contents": "Treatment of murine coccidioidomycosis with polymyxin B. An agar dilution method was employed to test the susceptibility of 12 strains of Coccidioides immitis to polymyxin B (PB). After 3 days of incubation, eight strains were markedly inhibited by 5.0 mug of PB per ml and four strains did not grow. PB at 10 mug/ml inhibited the growth of all strains through 20 days of incubation. To determine whether PB has anticoccidioidal activity in vivo, mice in groups of 30 were infected intraperitoneally with a mean lethal dose (LD(50)) or 20 LD(50) of arthrospores of C. immitis ATCC 28868 (Silveira). Treatment by intraperitoneal injection of PB (2.5 mg/kg) was begun 2 or 5 days after challenge. By 40 days after infection, 47 and 7% of the untreated mice challenged with an LD(50), respectively, were alive. Of mice infected with an LD(50) or 20 LD(50) and treated with PB beginning 2 days after the challenge, 90% of each group were alive by day 40. Initiation of PB therapy 5 days after infection permitted survival of 84% of the mice infected with an LD(50); however, only 27% of the mice infected with 20 LD(50) survived by day 40. In this latter group there was evidence that PB prolonged life since 56% of the treated mice were alive by day 15 as compared with 30% of the controls. PB in vivo was fungistatic since the majority of treated mice had C. immitis in the liver, lungs, and spleen."}
{"id": "PMID:185951", "title": "Effect of treatment with exogenous interferon, polyinosinic acid-polyctyidylic acid or polyinosinic acid-polycytidylic acid-poly-L-lysine complex on encephalomyocarditis virus infections in mice.", "content": "The effect of treatment with exogenous interferon was compared with two interferon inducers, polyinosinic acid-polycytidylic acid [poly(I:C)] and [poly(I:C)]-poly-l-lysine complex (P-L-L complex), in two model encephalomyocarditis virus infections of mice. Although both inducers stimulated the production of interferon, the peak serum levels induced by P-L-L complex were five- to eightfold greater than those induced with poly(I:C). When encephalomyocarditis virus was inoculated by either the intraperitoneal or the intranasal route, interferon and both of the inducers protected mice against mortality and prolonged the mean day of death when the compounds were given prior to or immediately after viral challenge. In general, treatment with interferon was not as successful as treatment with poly(I:C) or P-L-L complex. In these infections, P-L-L complex appeared to be the most effective agent in that successful treatment resulted when drug therapy was initiated as late as 48 h after virus inoculation. An examination of the effect of treatment on the pathogenesis of the infection indicated that protection was associated with the prevention of viremia and subsequent seeding of target organs, particularly the central nervous system.", "contents": "Effect of treatment with exogenous interferon, polyinosinic acid-polyctyidylic acid or polyinosinic acid-polycytidylic acid-poly-L-lysine complex on encephalomyocarditis virus infections in mice. The effect of treatment with exogenous interferon was compared with two interferon inducers, polyinosinic acid-polycytidylic acid [poly(I:C)] and [poly(I:C)]-poly-l-lysine complex (P-L-L complex), in two model encephalomyocarditis virus infections of mice. Although both inducers stimulated the production of interferon, the peak serum levels induced by P-L-L complex were five- to eightfold greater than those induced with poly(I:C). When encephalomyocarditis virus was inoculated by either the intraperitoneal or the intranasal route, interferon and both of the inducers protected mice against mortality and prolonged the mean day of death when the compounds were given prior to or immediately after viral challenge. In general, treatment with interferon was not as successful as treatment with poly(I:C) or P-L-L complex. In these infections, P-L-L complex appeared to be the most effective agent in that successful treatment resulted when drug therapy was initiated as late as 48 h after virus inoculation. An examination of the effect of treatment on the pathogenesis of the infection indicated that protection was associated with the prevention of viremia and subsequent seeding of target organs, particularly the central nervous system."}
{"id": "PMID:185952", "title": "Differential effects of 5-methylmercapto-2'-deoxyuridine on the replication of herpes simplex virus type 1 in two cell systems.", "content": "5-Methylmercapto-2'-deoxyuridine (MeMUdR), a structural analogue of thymidine (TdR), inhibits herpes simplex virus type 1 production in mouse L (Lb) cells at concentrations that are not inhibitory to viral growth in monkey kidney (CV-1) cells. It is moderately toxic to Lb cells but not to CV-1 cells at a concentration that causes 95% inhibition of viral replication in Lb cells. MeMUdR is incorporated into cellular and viral deoxyribonucleic acid (DNA) in both systems, but to a significantly higher level (compared with thymidine) in Lb cells. These results indicate that MeMUdR is a substrate for enzymes leading to DNA synthesis and suggest that the biological function of herpes simplex virus type 1 DNA is impaired only when the incorporation of MeMUdR into the DNA reaches a relatively high level.", "contents": "Differential effects of 5-methylmercapto-2'-deoxyuridine on the replication of herpes simplex virus type 1 in two cell systems. 5-Methylmercapto-2'-deoxyuridine (MeMUdR), a structural analogue of thymidine (TdR), inhibits herpes simplex virus type 1 production in mouse L (Lb) cells at concentrations that are not inhibitory to viral growth in monkey kidney (CV-1) cells. It is moderately toxic to Lb cells but not to CV-1 cells at a concentration that causes 95% inhibition of viral replication in Lb cells. MeMUdR is incorporated into cellular and viral deoxyribonucleic acid (DNA) in both systems, but to a significantly higher level (compared with thymidine) in Lb cells. These results indicate that MeMUdR is a substrate for enzymes leading to DNA synthesis and suggest that the biological function of herpes simplex virus type 1 DNA is impaired only when the incorporation of MeMUdR into the DNA reaches a relatively high level."}
{"id": "PMID:185953", "title": "Antiviral activity of BL-3849A, a low-molecular-weight oral interferon inducer.", "content": "Oral administration of BL-3849A to adult mice resulted in peak serum interferon titers of 4,000 units from 15 to 30 h after administration, with detectable levels persisting until 48 h. After intraperitoneal (i.p.) inoculation, peak serum interferon titers of 1,000 to 3,000 units were noted between 9 and 18 h. Multiple injections of the inducer by either route resulted in a marked decrease in the interferon response with each successive dose. In mice infected intranasally with the Rochester mouse virus strain of encephalomyocarditis virus, oral treatment with BL-3849A reduced mortality when initiated either 18 h before or 1 h after infection. In contrast, administration of drug by the i.p. route decreased mortality only if begun before infection. In mice inoculated i.p. with encephalomyocarditis virus, treatment by both the oral and the i.p. route decreased the mortality whether initiated 18 h before or 1 h after infection. Treatment by the oral, but not the i.p., route reduced mortality of mice inoculated i.p. with Semliki forest virus or Herpesvirus hominis type 2. BL-3849A appeared to be as effective as tilorone hydrochloride, but less effective than polyriboinosinic-polyribocytidylic acid, in the treatment of these viral infections of mice.", "contents": "Antiviral activity of BL-3849A, a low-molecular-weight oral interferon inducer. Oral administration of BL-3849A to adult mice resulted in peak serum interferon titers of 4,000 units from 15 to 30 h after administration, with detectable levels persisting until 48 h. After intraperitoneal (i.p.) inoculation, peak serum interferon titers of 1,000 to 3,000 units were noted between 9 and 18 h. Multiple injections of the inducer by either route resulted in a marked decrease in the interferon response with each successive dose. In mice infected intranasally with the Rochester mouse virus strain of encephalomyocarditis virus, oral treatment with BL-3849A reduced mortality when initiated either 18 h before or 1 h after infection. In contrast, administration of drug by the i.p. route decreased mortality only if begun before infection. In mice inoculated i.p. with encephalomyocarditis virus, treatment by both the oral and the i.p. route decreased the mortality whether initiated 18 h before or 1 h after infection. Treatment by the oral, but not the i.p., route reduced mortality of mice inoculated i.p. with Semliki forest virus or Herpesvirus hominis type 2. BL-3849A appeared to be as effective as tilorone hydrochloride, but less effective than polyriboinosinic-polyribocytidylic acid, in the treatment of these viral infections of mice."}
{"id": "PMID:185954", "title": "Therapeutic effects of small-particle aerosols of ribavirin on parainfluenza (sendai) virus infections of mice.", "content": "Small-particle aerosol administration of ribavirin (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) increased survival rates, extended the time to death, delayed lung pathology, and reduced pulmonary virus levels in Sendai virus-infected mice.", "contents": "Therapeutic effects of small-particle aerosols of ribavirin on parainfluenza (sendai) virus infections of mice. Small-particle aerosol administration of ribavirin (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) increased survival rates, extended the time to death, delayed lung pathology, and reduced pulmonary virus levels in Sendai virus-infected mice."}
{"id": "PMID:185956", "title": "Heat inactivation of poliovirus in wastewater sludge.", "content": "The effect of raw and anaerobically digested sludge on heat inactivation of poliovirus was investigated. Raw sludge was found to be very protective of poliovirus plaque-forming ability at all temperatures studied, but digested sludge had variable effects that were highly dependent upon the experimental conditions. In low concentrations and at relatively low inactivation temperatures, digested sludge is nearly as protective of poliovirus as raw sludge. However, at higher tempeatures and concentrations, digested sludge caused a significant acceleration of poliovirus inactivation. The difference between the protective capability of raw and digested sludge is not due to loss of protective material, because this component is present in the solids of digested sludge as well as in those of raw sludge. Instead, the difference is due to a virucidal agent acquired during digestion. Addition of this agent to the solids of either raw or digested sludge reverses the protective potential of these solids during heat treatment of poliovirus.", "contents": "Heat inactivation of poliovirus in wastewater sludge. The effect of raw and anaerobically digested sludge on heat inactivation of poliovirus was investigated. Raw sludge was found to be very protective of poliovirus plaque-forming ability at all temperatures studied, but digested sludge had variable effects that were highly dependent upon the experimental conditions. In low concentrations and at relatively low inactivation temperatures, digested sludge is nearly as protective of poliovirus as raw sludge. However, at higher tempeatures and concentrations, digested sludge caused a significant acceleration of poliovirus inactivation. The difference between the protective capability of raw and digested sludge is not due to loss of protective material, because this component is present in the solids of digested sludge as well as in those of raw sludge. Instead, the difference is due to a virucidal agent acquired during digestion. Addition of this agent to the solids of either raw or digested sludge reverses the protective potential of these solids during heat treatment of poliovirus."}
{"id": "PMID:185957", "title": "Silica gel medium to detect molds that produce aflatoxin.", "content": "A chemically defined nutrient solution containing tartaric acid was made solid by mixing it with an alkaline silicate solution. Production of aflatoxin by asperfilli growing on the silica gel medium coincided with the presence of a blue fluorescent area surrounding colonies, as observed under long-wave ultraviolet light. Presence of aflatoxin in the medium was confirmed by drying the gels, extracting them with chloroform-methanol, and examining extracts for fluorescent materials by viewing them on thin-layer chromatograms under ultraviolet light.", "contents": "Silica gel medium to detect molds that produce aflatoxin. A chemically defined nutrient solution containing tartaric acid was made solid by mixing it with an alkaline silicate solution. Production of aflatoxin by asperfilli growing on the silica gel medium coincided with the presence of a blue fluorescent area surrounding colonies, as observed under long-wave ultraviolet light. Presence of aflatoxin in the medium was confirmed by drying the gels, extracting them with chloroform-methanol, and examining extracts for fluorescent materials by viewing them on thin-layer chromatograms under ultraviolet light."}
{"id": "PMID:185958", "title": "Beneficial effect of catalase treatment on growth of Clostridium perfringens.", "content": "Several common plating media were tested for their ability to support growth of Clostridium perfringens after storage of the plates for 1 to 10 days at 4 and 25 degrees C with and without subsequent addition of catalase. Liver-veal (LV) agar and brain heart infusion (BHI) agar quickly become incapable of supporting growth after storage without added catalase, whereas Shahidi Ferguson perfringens (SFP) agar and Brewer anaerobic (BA) agar were less affected. Plate counts of C. perfringens on untreated LV and BHI agars stored 3 days at 25 degrees C showed a reduction of 98.2%, whereas counts on SFP and BA agars were reduced by 13.6% and 46.2%, respectively. Addition of 1,500 U of beef liver catalase to the surface of the 3-day-old agars before incubation resulted in substantial restoration of their growth-promoting ability. Counts of colonies on LV, GHI, SFP, and BA agars with added catalase were usually 20 to 90% higher than untreated controls. Similar results were obtained using purified catalase, fungal catalase, and horseradish peroxidase. These results suggest that inhibition may be due to peroxide formed during storage and incubation and that additon of catalase provides near optimum conditions for growth of C. perfringens on these media.", "contents": "Beneficial effect of catalase treatment on growth of Clostridium perfringens. Several common plating media were tested for their ability to support growth of Clostridium perfringens after storage of the plates for 1 to 10 days at 4 and 25 degrees C with and without subsequent addition of catalase. Liver-veal (LV) agar and brain heart infusion (BHI) agar quickly become incapable of supporting growth after storage without added catalase, whereas Shahidi Ferguson perfringens (SFP) agar and Brewer anaerobic (BA) agar were less affected. Plate counts of C. perfringens on untreated LV and BHI agars stored 3 days at 25 degrees C showed a reduction of 98.2%, whereas counts on SFP and BA agars were reduced by 13.6% and 46.2%, respectively. Addition of 1,500 U of beef liver catalase to the surface of the 3-day-old agars before incubation resulted in substantial restoration of their growth-promoting ability. Counts of colonies on LV, GHI, SFP, and BA agars with added catalase were usually 20 to 90% higher than untreated controls. Similar results were obtained using purified catalase, fungal catalase, and horseradish peroxidase. These results suggest that inhibition may be due to peroxide formed during storage and incubation and that additon of catalase provides near optimum conditions for growth of C. perfringens on these media."}
{"id": "PMID:185959", "title": "Fine structure of the Baccilus thuringiensis spore.", "content": "The thin-sectioned spore of Bacillus thuringiensis resembles that of Bacillus cereus in fine structure. Planar inclusions occur between the exosporium and spore coat and are structured differently from the parasporal crystal outside the exosporium.", "contents": "Fine structure of the Baccilus thuringiensis spore. The thin-sectioned spore of Bacillus thuringiensis resembles that of Bacillus cereus in fine structure. Planar inclusions occur between the exosporium and spore coat and are structured differently from the parasporal crystal outside the exosporium."}
{"id": "PMID:185960", "title": "Virus movement in soil columns flooded with secondary sewage effluent.", "content": "Secondary sewage effluent containing about 3 X 10(4) plaque-forming units of polio virus type 1 (LSc) per ml was passed through columns 250 cm in length packed with calcareous sand from an area in the Salt River bed used for ground-water recharge of secondary sewage effluent. Viruses were not detected in 1-ml samples extracted from the columns below the 160-cm level. However, viruses were detected in 5 of 43 100-ml samples of the column drainage water. Most of the viruses were adsorbed in the top 5 cm of soil. Virus removal was not affected by the infiltration rate, which varied between 15 and 55 cm/day. Flooding a column continuosly for 27 days with the sewage water virus mixture did not saturate the top few centimeters of soil with viruses and did not seem to affect virus movement. Flooding with deionized water caused virus desorption from the soil and increased their movement through the columns. Adding CaCl2 to the deionized water prevented most of the virus desorption. Adding a pulse of deionized water followed by sewage water started a virus front moving through the columns, but the viruses were readsorbed and none was detected in outflow samples. Drying the soil for 1 day between applying the virus and flooding with deionized water greatly reduced desorption, and drying for 5 days prevented desorption. Large reductions (99.99% or more) of virus would be expected after passage of secondary sewage effluent through 250 cm of the calcareous sand similar to that used in our laboratory columns unless heavy rains fell within 1 day after the application of sewage stopped. Such virus movement could be minimized by the proper management of flooding and drying cycles.", "contents": "Virus movement in soil columns flooded with secondary sewage effluent. Secondary sewage effluent containing about 3 X 10(4) plaque-forming units of polio virus type 1 (LSc) per ml was passed through columns 250 cm in length packed with calcareous sand from an area in the Salt River bed used for ground-water recharge of secondary sewage effluent. Viruses were not detected in 1-ml samples extracted from the columns below the 160-cm level. However, viruses were detected in 5 of 43 100-ml samples of the column drainage water. Most of the viruses were adsorbed in the top 5 cm of soil. Virus removal was not affected by the infiltration rate, which varied between 15 and 55 cm/day. Flooding a column continuosly for 27 days with the sewage water virus mixture did not saturate the top few centimeters of soil with viruses and did not seem to affect virus movement. Flooding with deionized water caused virus desorption from the soil and increased their movement through the columns. Adding CaCl2 to the deionized water prevented most of the virus desorption. Adding a pulse of deionized water followed by sewage water started a virus front moving through the columns, but the viruses were readsorbed and none was detected in outflow samples. Drying the soil for 1 day between applying the virus and flooding with deionized water greatly reduced desorption, and drying for 5 days prevented desorption. Large reductions (99.99% or more) of virus would be expected after passage of secondary sewage effluent through 250 cm of the calcareous sand similar to that used in our laboratory columns unless heavy rains fell within 1 day after the application of sewage stopped. Such virus movement could be minimized by the proper management of flooding and drying cycles."}
{"id": "PMID:185961", "title": "Agar plate tests of enhanced sensitivity for detecting biologically active products of staphylococcal filtrates.", "content": "Optimal conditions for detecting staphylokinase, phosphatase, protease, lipase, esterase, egg yolk factor, lysozyme, deoxyribonuclease, hyaluronidase, penicillinase, and alpha-, beta-, and delta-hemolysins in cell-free filtrates of selected strains of staphylococci by agar plate methods were established by studying the effect of factors such as buffer composition, pH, ionic strength, type of agar, nature and concentration of substrate, and certain metal ions. The final tests that evolved from this study are simple to perform, require only 6 mul of the sample per test, and are capable of detecting microgram and, in some cases, nanogram quantities of the product. The zones of reaction can also be quantitatively related to the amount of material present. The test may also be useful for the detection of extracellular products of other microorganisms.", "contents": "Agar plate tests of enhanced sensitivity for detecting biologically active products of staphylococcal filtrates. Optimal conditions for detecting staphylokinase, phosphatase, protease, lipase, esterase, egg yolk factor, lysozyme, deoxyribonuclease, hyaluronidase, penicillinase, and alpha-, beta-, and delta-hemolysins in cell-free filtrates of selected strains of staphylococci by agar plate methods were established by studying the effect of factors such as buffer composition, pH, ionic strength, type of agar, nature and concentration of substrate, and certain metal ions. The final tests that evolved from this study are simple to perform, require only 6 mul of the sample per test, and are capable of detecting microgram and, in some cases, nanogram quantities of the product. The zones of reaction can also be quantitatively related to the amount of material present. The test may also be useful for the detection of extracellular products of other microorganisms."}
{"id": "PMID:185972", "title": "Demonstration of antibodies to collagen and of collagen-anticollagen immune complexes in rheumatoid arthritis synovial fluids.", "content": "Twenty-nine synovial fluids from patients with rheumatoid arthritis (RA) and 10 synovial fluids from patients with other joint diseases were investigated with regard to the presence of antibodies to denatured human collagen and of collagen-anticollagen immune complexes. 12 of the 29 RA synovial fluids showed anticollagen titres from 1:16 to 1:512 in passive haemagglutination. Only one patient in the group with no arthritis had a significant anticollagen titre of 1:32. Digestion of the synovial fluids with bacterial collagenase resulted in an anticollagen titre increase from two to four dilution steps in 9 of the RA fluids, while 6 previously negative RA synovial fluids showed anticollagen titres from 1:32 to 1:28 after digestion with collagenase. These results indicate the existence of collagen-anticollagen immune complexes in 15 of the 29 RA synovial fluids investigated.", "contents": "Demonstration of antibodies to collagen and of collagen-anticollagen immune complexes in rheumatoid arthritis synovial fluids. Twenty-nine synovial fluids from patients with rheumatoid arthritis (RA) and 10 synovial fluids from patients with other joint diseases were investigated with regard to the presence of antibodies to denatured human collagen and of collagen-anticollagen immune complexes. 12 of the 29 RA synovial fluids showed anticollagen titres from 1:16 to 1:512 in passive haemagglutination. Only one patient in the group with no arthritis had a significant anticollagen titre of 1:32. Digestion of the synovial fluids with bacterial collagenase resulted in an anticollagen titre increase from two to four dilution steps in 9 of the RA fluids, while 6 previously negative RA synovial fluids showed anticollagen titres from 1:32 to 1:28 after digestion with collagenase. These results indicate the existence of collagen-anticollagen immune complexes in 15 of the 29 RA synovial fluids investigated."}
{"id": "PMID:185973", "title": "Calcium and phosphorus homeostasis in man. Effect of corticosteroids.", "content": "Serum calcium and phosphorus levels, urinary excretion rates of calcium, phosphorus, and cyclic adenosine monophosphate (cAMP), and plasma parathyroid hormone (PTH) concentrations were determined in 11 normal subjects and in nine patients maintained on long-term prednisone therapy for chronic obstructive pulmonary disease. These same determinations were repeated in five of the prednisone-treated patients during the course of a seven-day calcium infusion. Prior to the infusion, the prednisone-treated patients demonstrated significantly elevated serum levels of PTH (P less than .005) and increased rates of urinary phosphate and cAMP excreation (P less than .005) when compared with normal subjects. After initiation of calcium infusion, the previous elevations in all of these determinations decreased to near normal levels. These data suggest that the effects of secondary hyperparathyroidism in patients maintained on long-term prednisone therapy may be overcome when calcium is administered intravenously.", "contents": "Calcium and phosphorus homeostasis in man. Effect of corticosteroids. Serum calcium and phosphorus levels, urinary excretion rates of calcium, phosphorus, and cyclic adenosine monophosphate (cAMP), and plasma parathyroid hormone (PTH) concentrations were determined in 11 normal subjects and in nine patients maintained on long-term prednisone therapy for chronic obstructive pulmonary disease. These same determinations were repeated in five of the prednisone-treated patients during the course of a seven-day calcium infusion. Prior to the infusion, the prednisone-treated patients demonstrated significantly elevated serum levels of PTH (P less than .005) and increased rates of urinary phosphate and cAMP excreation (P less than .005) when compared with normal subjects. After initiation of calcium infusion, the previous elevations in all of these determinations decreased to near normal levels. These data suggest that the effects of secondary hyperparathyroidism in patients maintained on long-term prednisone therapy may be overcome when calcium is administered intravenously."}
{"id": "PMID:185974", "title": "Herpesvirus hominis hepatitis and disseminated intravascular coagulation. Occurrence in an adult with pemphigus vulgaris.", "content": "Herpesvirus hominis (HVH) hepatitis, a rarely recognized manifestation of HVH infection in adults, occurred in a 36-year-old woman who had received prednisone therapy for pemphigus vulgaris continuously for seven years. After an acute terminal illness that was characterized by fulminant hepatic failure and disseminated intravascular coagulation (DIC), postmortem examination disclosed massive hepatic necrosis. Herpesvirus hominis (type 1) was isolated from the liver. The association of disseminated HVH infection with impaired immunologic defenses, as well as the occurrence of DIC in association with acute hepatic failure, are discussed. Greater awareness of the clinical manifestations of HVH hepatitis should lead to early diagnosis, although sucessful modes of therapy await development.", "contents": "Herpesvirus hominis hepatitis and disseminated intravascular coagulation. Occurrence in an adult with pemphigus vulgaris. Herpesvirus hominis (HVH) hepatitis, a rarely recognized manifestation of HVH infection in adults, occurred in a 36-year-old woman who had received prednisone therapy for pemphigus vulgaris continuously for seven years. After an acute terminal illness that was characterized by fulminant hepatic failure and disseminated intravascular coagulation (DIC), postmortem examination disclosed massive hepatic necrosis. Herpesvirus hominis (type 1) was isolated from the liver. The association of disseminated HVH infection with impaired immunologic defenses, as well as the occurrence of DIC in association with acute hepatic failure, are discussed. Greater awareness of the clinical manifestations of HVH hepatitis should lead to early diagnosis, although sucessful modes of therapy await development."}
{"id": "PMID:185975", "title": "Isolation and purification of reaction center from Rhodopseudomonas viridis NHTC 133 by means of LDAO.", "content": "Two different procedures are described to isolate and purify the reaction center complex from Rhodopseudomonas viridis NHTC 133 by means of the non-ionic detergent dodecyldimethylamine oxide. Both reaction center particles thus obtained were active, as shown by a photobleaching centered at 975 nm. The reaction center also contained, in addition to bacteriochlorophyll, bacteriopheophytin. Other components were also found in this particle: cytochromes C553 and C558 and a menaquinone-like substance. The SDS gel electrophoresis of reaction centers is shown. The molecular weights of the subunits forming the reaction center in 0.5% sodium dodecyl sulfate and 1% mercaptoethanol were calculated as being: 45 +/- 1.5 and 37 +/- 1.5 kdalton, 29 +/- 1.5 and 23 +/- 1.5 kdalton. The molecular weight of the complex determined by means of gel filtration (Sepharose 6-B and Bio-Gel P-300) gives a value of approximately 240 kdalton. The minimum molecular weight of the complex calculated by disc gel electrophoresis was 231 kdalton.", "contents": "Isolation and purification of reaction center from Rhodopseudomonas viridis NHTC 133 by means of LDAO. Two different procedures are described to isolate and purify the reaction center complex from Rhodopseudomonas viridis NHTC 133 by means of the non-ionic detergent dodecyldimethylamine oxide. Both reaction center particles thus obtained were active, as shown by a photobleaching centered at 975 nm. The reaction center also contained, in addition to bacteriochlorophyll, bacteriopheophytin. Other components were also found in this particle: cytochromes C553 and C558 and a menaquinone-like substance. The SDS gel electrophoresis of reaction centers is shown. The molecular weights of the subunits forming the reaction center in 0.5% sodium dodecyl sulfate and 1% mercaptoethanol were calculated as being: 45 +/- 1.5 and 37 +/- 1.5 kdalton, 29 +/- 1.5 and 23 +/- 1.5 kdalton. The molecular weight of the complex determined by means of gel filtration (Sepharose 6-B and Bio-Gel P-300) gives a value of approximately 240 kdalton. The minimum molecular weight of the complex calculated by disc gel electrophoresis was 231 kdalton."}
{"id": "PMID:185976", "title": "The effect of transfer from low to high light intensity on electron transport in Rhodospirillum rubrum membranes.", "content": "The effects of transfer from low to high light intensity on membrane bound electrontransport reactions of Rhodospirillum rubrum were investigated. The experiments were performed with cultures which did not form bacteriochlorophyll (Bchl) for about two cell mass doublings during the initial phase of adaptation to high light intensity. Lack of Bchl synthesis causes a decrease of Bchl contents of cells and membranes. Also, the cellular amounts of photosynthetically active intracytoplasmic membranes decrease. In crude membrane fractions containing both cytoplasmic and intracytoplasmic membranes the initial activities of NADH oxidizing reactions increase only slightly (about 1.2 times) per protein, but the initial activities of succinate oxidizing reactions decrease (multiplied by a factor of 0.7). On a Bchl basis activities of NADH oxidizing reactions increase 3.4 times while activities of succinate dependent reactions increase 1.9 times. With isolated intracytoplasmic membranes activities of NADH as well as succinate dependent reactions increase to a comparable extent on a Bchl basis (about 1.8 times) and stay nearly constant on a protein basis. Cyochrome c oxidase responds like succinate dependent reactions. The data indicate that in cells growing under the conditions applied NADH oxidizing electrontransport systems are incorporated into both, cytoplasmic and intracytoplasmic membranes, while incorporation of succinate oxidizing systems is confined to intracytoplasmic membranes only. Activities of photophosphorylation and succinate dependent NAD+ reduction in the light increase per Bchl about 1.8 times. On a Bchl basis increases of the fast light induced \"on\" reactions at 422 nm and increases of soluble cytochrome c2 levels are comparable to increases of photophosphorylations and succinate dependent activities. But increases of slow light \"off\" reactions at 428 nm and of beta-type cytochrome levels become three times greater then increases of cytochrome c2 reactions and levels. These results infer that although electrontransport reactions of intracytoplasmic membranes change correlated to each other, Bchl, cytochrome c2 and beta-type cytochromes cellular levels are independent of each other. Furthermore, the data indicate that cytochrome c2 rather than beta-type cytochrome is involved with steps rate limiting for photophosphorylation.", "contents": "The effect of transfer from low to high light intensity on electron transport in Rhodospirillum rubrum membranes. The effects of transfer from low to high light intensity on membrane bound electrontransport reactions of Rhodospirillum rubrum were investigated. The experiments were performed with cultures which did not form bacteriochlorophyll (Bchl) for about two cell mass doublings during the initial phase of adaptation to high light intensity. Lack of Bchl synthesis causes a decrease of Bchl contents of cells and membranes. Also, the cellular amounts of photosynthetically active intracytoplasmic membranes decrease. In crude membrane fractions containing both cytoplasmic and intracytoplasmic membranes the initial activities of NADH oxidizing reactions increase only slightly (about 1.2 times) per protein, but the initial activities of succinate oxidizing reactions decrease (multiplied by a factor of 0.7). On a Bchl basis activities of NADH oxidizing reactions increase 3.4 times while activities of succinate dependent reactions increase 1.9 times. With isolated intracytoplasmic membranes activities of NADH as well as succinate dependent reactions increase to a comparable extent on a Bchl basis (about 1.8 times) and stay nearly constant on a protein basis. Cyochrome c oxidase responds like succinate dependent reactions. The data indicate that in cells growing under the conditions applied NADH oxidizing electrontransport systems are incorporated into both, cytoplasmic and intracytoplasmic membranes, while incorporation of succinate oxidizing systems is confined to intracytoplasmic membranes only. Activities of photophosphorylation and succinate dependent NAD+ reduction in the light increase per Bchl about 1.8 times. On a Bchl basis increases of the fast light induced \"on\" reactions at 422 nm and increases of soluble cytochrome c2 levels are comparable to increases of photophosphorylations and succinate dependent activities. But increases of slow light \"off\" reactions at 428 nm and of beta-type cytochrome levels become three times greater then increases of cytochrome c2 reactions and levels. These results infer that although electrontransport reactions of intracytoplasmic membranes change correlated to each other, Bchl, cytochrome c2 and beta-type cytochromes cellular levels are independent of each other. Furthermore, the data indicate that cytochrome c2 rather than beta-type cytochrome is involved with steps rate limiting for photophosphorylation."}
{"id": "PMID:185977", "title": "Studies about the adjuvant activity of saponin fractions in foot and mouth disease vaccine. III. Comparison of the irritant, adjuvant and hemolytic activities of six commercial saponins and their hemolytic fractions obtained by chromatography on sephadex G 100.", "content": "12 experimental vaccines were prepared to compare the irritant and adjuvant activity in cattle of 6 commercial saponin preparations and their hemolytic fractions. It is still not known if a single substance is responsible for the irritant, adjuvant and hemolytic activities of the saponin preparations. The quantities of saponin added were standardised on the base of a constant hemolytic activity rather than on a weight of powder per dose of vaccine base. A FMD vaccine was used to reveal the adjuvant activity. It was concluded that the irritation is related to the hemolytic activity and not to the weight of powder. Irritation is slightly reduced when a toxic effect appears. The adjuvant activity was higher for untreated saponin preparations with high hemolytic activity used at low dose and for one of the chromatographic saponin fractions. The adjuvant activity is reduced when toxic effect appear. Toxicity of less hemolytic saponins used at high dose is removed by chromatography. Highly hemolytic saponins used at low dose become toxic after chromatographic treatment.", "contents": "Studies about the adjuvant activity of saponin fractions in foot and mouth disease vaccine. III. Comparison of the irritant, adjuvant and hemolytic activities of six commercial saponins and their hemolytic fractions obtained by chromatography on sephadex G 100. 12 experimental vaccines were prepared to compare the irritant and adjuvant activity in cattle of 6 commercial saponin preparations and their hemolytic fractions. It is still not known if a single substance is responsible for the irritant, adjuvant and hemolytic activities of the saponin preparations. The quantities of saponin added were standardised on the base of a constant hemolytic activity rather than on a weight of powder per dose of vaccine base. A FMD vaccine was used to reveal the adjuvant activity. It was concluded that the irritation is related to the hemolytic activity and not to the weight of powder. Irritation is slightly reduced when a toxic effect appears. The adjuvant activity was higher for untreated saponin preparations with high hemolytic activity used at low dose and for one of the chromatographic saponin fractions. The adjuvant activity is reduced when toxic effect appear. Toxicity of less hemolytic saponins used at high dose is removed by chromatography. Highly hemolytic saponins used at low dose become toxic after chromatographic treatment."}
{"id": "PMID:185978", "title": "Routine titration of foot and mouth disease virus suspensions by analytical ultracentrifugation. 1: Sedimentation method.", "content": "Infectivity and Complement Fixation (CF) tests are commonly used for the routine titration of Foot and Mouth Disease (FMD) virus suspensions. Only recently were techniques published for the routine determination of the virus concentration by the physical properties of the virions (Fayet et al., 1971; Barteling et al., 1974). These techniques are based on the separation of the  virions from the culture fluid by sedimentation through a sucrose gradient, in a preparative ultracentrifuge. The ultraviolet absorption pattern of the tube content is recorded by a flow colorimeter. The virus concentration is estimated using either standard curves or direct caculation by the specific extinction coefficient (Bachrach et al., 1964). In our own attempts to develop a preparative ultracentrifugation technique for the routine titration of FMD virus suspensions, we had to deal with some problems such as remixing of the virus band at the end of the run. We therefore turned over to analytical ultracentrifugation methods. The manipulations are less complicated and the virus band is traced and measured while the rotor is spinning. Four samples are analyzed simultaneously and the scans are repeated to follow the move of the virus band. The sedimentation rate of the virus band, calculated from the repeated scans, helps to detect artifacts. The present paper describes the technique we developed for the routine titration of FMD virus suspensions, by the band sedimentation method, using an ultraviolet scanning analytical ultracentrifuge.", "contents": "Routine titration of foot and mouth disease virus suspensions by analytical ultracentrifugation. 1: Sedimentation method. Infectivity and Complement Fixation (CF) tests are commonly used for the routine titration of Foot and Mouth Disease (FMD) virus suspensions. Only recently were techniques published for the routine determination of the virus concentration by the physical properties of the virions (Fayet et al., 1971; Barteling et al., 1974). These techniques are based on the separation of the  virions from the culture fluid by sedimentation through a sucrose gradient, in a preparative ultracentrifuge. The ultraviolet absorption pattern of the tube content is recorded by a flow colorimeter. The virus concentration is estimated using either standard curves or direct caculation by the specific extinction coefficient (Bachrach et al., 1964). In our own attempts to develop a preparative ultracentrifugation technique for the routine titration of FMD virus suspensions, we had to deal with some problems such as remixing of the virus band at the end of the run. We therefore turned over to analytical ultracentrifugation methods. The manipulations are less complicated and the virus band is traced and measured while the rotor is spinning. Four samples are analyzed simultaneously and the scans are repeated to follow the move of the virus band. The sedimentation rate of the virus band, calculated from the repeated scans, helps to detect artifacts. The present paper describes the technique we developed for the routine titration of FMD virus suspensions, by the band sedimentation method, using an ultraviolet scanning analytical ultracentrifuge."}
{"id": "PMID:185979", "title": "[Cytological and histochemical studies on cell cultures infected with bovine herpesvirus type 2].", "content": "Cell cultures of embryonic calf kidney which had been infected with bovid herpes virus 2 were examined for cytological and histochemical changes. The morphological changes recorded from cells damaged by virus infection included the formation of gigant syncytial cells and intranuclear inclusions of Cowdry Type A. The cytological changes in the infected cells were accompanied by variation in enzyme activity. Recordable were rise in lactate dehydrogenase and alkaline phosphatase as well as decline in succinate dehydrogenase and acid phosphate activity. These phenomena were found to have resulted from impediment of cell metabolism by virus action.", "contents": "[Cytological and histochemical studies on cell cultures infected with bovine herpesvirus type 2]. Cell cultures of embryonic calf kidney which had been infected with bovid herpes virus 2 were examined for cytological and histochemical changes. The morphological changes recorded from cells damaged by virus infection included the formation of gigant syncytial cells and intranuclear inclusions of Cowdry Type A. The cytological changes in the infected cells were accompanied by variation in enzyme activity. Recordable were rise in lactate dehydrogenase and alkaline phosphatase as well as decline in succinate dehydrogenase and acid phosphate activity. These phenomena were found to have resulted from impediment of cell metabolism by virus action."}
{"id": "PMID:185980", "title": "[Micro-epidemiology and micro-plaque titration of infectious bovine rhinotracheitis virus on primary calf kidney cells by means of immunofluorescence].", "content": "Immunofluorescence was used to study the virus of infectious bovine rhinotracheitis and the course of infection in cell cultures of calf kidney. An indirect relationship was found to exist between the magnitude of inoculation and the onset of specific fluorescence. Fluorescent plaques are formed as a result of inoculate dilution. The plaques will grow along with incubation time. Release of virus into the culturing medium will first lead to the formation of secondary plaques, then followed by generalised infection of the cell culture. The time at which the infection will begin to be disseminated was found to depend on both multiplicity of the infection and quality of the cell culture. Therefore, no limitation is possible of the time during which only primary infectious foci are recordable. Antibody present in the culturing medium prevent propagation of the infection, but this does not inhibit the course of primary infection nor intercellular virus transmission. The conditions are defined for the microplaque fluorescence method and its use on quantitative virus assay. While reproducible results are offered by that method, its sensitivity is below that of the tubule method, when it comes to identifying the infection due to the cytopathic effect. The microplaque fluorescence method was used to study the conditions for absorption of virus of infectious bovine rhinotracheitis by calf-kidney cell cultures. Absorption was tested under temperatures of 20 degrees C, 37 degrees C, and 40 degrees C and found to be accelerated by higher temperatures. Yet, the total quantity of virus absorbed in 120 minutes was found to be almost the same in all three temperatures. The degree of virus absorption was found to depend on the kind of medium, with the rate of absorption having been strongly increased by adding to the medium serum of different animal species. About 70 per cent of the virus present in the inoculate were absorbed by the calf-kidney cell cultures under defined experimental conditions.", "contents": "[Micro-epidemiology and micro-plaque titration of infectious bovine rhinotracheitis virus on primary calf kidney cells by means of immunofluorescence]. Immunofluorescence was used to study the virus of infectious bovine rhinotracheitis and the course of infection in cell cultures of calf kidney. An indirect relationship was found to exist between the magnitude of inoculation and the onset of specific fluorescence. Fluorescent plaques are formed as a result of inoculate dilution. The plaques will grow along with incubation time. Release of virus into the culturing medium will first lead to the formation of secondary plaques, then followed by generalised infection of the cell culture. The time at which the infection will begin to be disseminated was found to depend on both multiplicity of the infection and quality of the cell culture. Therefore, no limitation is possible of the time during which only primary infectious foci are recordable. Antibody present in the culturing medium prevent propagation of the infection, but this does not inhibit the course of primary infection nor intercellular virus transmission. The conditions are defined for the microplaque fluorescence method and its use on quantitative virus assay. While reproducible results are offered by that method, its sensitivity is below that of the tubule method, when it comes to identifying the infection due to the cytopathic effect. The microplaque fluorescence method was used to study the conditions for absorption of virus of infectious bovine rhinotracheitis by calf-kidney cell cultures. Absorption was tested under temperatures of 20 degrees C, 37 degrees C, and 40 degrees C and found to be accelerated by higher temperatures. Yet, the total quantity of virus absorbed in 120 minutes was found to be almost the same in all three temperatures. The degree of virus absorption was found to depend on the kind of medium, with the rate of absorption having been strongly increased by adding to the medium serum of different animal species. About 70 per cent of the virus present in the inoculate were absorbed by the calf-kidney cell cultures under defined experimental conditions."}
{"id": "PMID:185981", "title": "[Cataract due to galactokinase deficiency in a premature infant].", "content": "Report of a case of galactosemia due to galactokinase deficiency. The author recalls the clinical (opacity of the lens) and biological features (important galactosuria, gallactiloluria, normal aminoaciduria, minimal hyperglycemia following galactose load). Since symptoms of increased intracranial pressure were present in this case, as in another one previously described, the commonly accepted statement that cataract is the only lesion in galactokinase deficiency must be reconsidered.", "contents": "[Cataract due to galactokinase deficiency in a premature infant]. Report of a case of galactosemia due to galactokinase deficiency. The author recalls the clinical (opacity of the lens) and biological features (important galactosuria, gallactiloluria, normal aminoaciduria, minimal hyperglycemia following galactose load). Since symptoms of increased intracranial pressure were present in this case, as in another one previously described, the commonly accepted statement that cataract is the only lesion in galactokinase deficiency must be reconsidered."}
{"id": "PMID:185984", "title": "Unusual cytoplasmic inclusions in blast cells in acute leukemia.", "content": "A 36-year-old man manifested the clinical signs of acute leukemia. Blast cells in the blood and bone marrow contained many large cytoplasmic inclusions. Cytochemical and ultrastructural studies indicated that the leukemic cells were of lymphocytic origin. Three kinds of inclusions were identified on electron microscopy: one type of inclusion contained virus-like particles; another resembled those in cases with hairy cell leukemia; and the third appeared to be autophagic in nature. The presence of the second type of inclusion in the blast cells and the relative chronicity of the clinical course suggest that this patient's disease is of lymphocytic origin, similar  to hairy cell leukemia.", "contents": "Unusual cytoplasmic inclusions in blast cells in acute leukemia. A 36-year-old man manifested the clinical signs of acute leukemia. Blast cells in the blood and bone marrow contained many large cytoplasmic inclusions. Cytochemical and ultrastructural studies indicated that the leukemic cells were of lymphocytic origin. Three kinds of inclusions were identified on electron microscopy: one type of inclusion contained virus-like particles; another resembled those in cases with hairy cell leukemia; and the third appeared to be autophagic in nature. The presence of the second type of inclusion in the blast cells and the relative chronicity of the clinical course suggest that this patient's disease is of lymphocytic origin, similar  to hairy cell leukemia."}
{"id": "PMID:185985", "title": "Ultrastructural observations of cytoplasmic inclusions in Tay-Sachs lymphocytes.", "content": "Our preliminary study on the circulating leukocytes from two children with Tay-Sachs disease and six heterozygotes from four different families is reported at the levels of both light and transmission electron microscopy. Ultrastructural investigation revealed two types of cytoplasmic inclusions in the lymphocytes of the Tay-Sachs homozygotes. The heterozygotes demonstrated only one of the inclusion forms within the cytoplasm of their circulating lymphocytes. These fine structural observations have not been described previously in Tay-Sachs disease and they may suggest new functional implications for the involvement of the lymphocyte in this storage disorder.", "contents": "Ultrastructural observations of cytoplasmic inclusions in Tay-Sachs lymphocytes. Our preliminary study on the circulating leukocytes from two children with Tay-Sachs disease and six heterozygotes from four different families is reported at the levels of both light and transmission electron microscopy. Ultrastructural investigation revealed two types of cytoplasmic inclusions in the lymphocytes of the Tay-Sachs homozygotes. The heterozygotes demonstrated only one of the inclusion forms within the cytoplasm of their circulating lymphocytes. These fine structural observations have not been described previously in Tay-Sachs disease and they may suggest new functional implications for the involvement of the lymphocyte in this storage disorder."}
{"id": "PMID:185986", "title": "Chloramphenicol-induced mitochondrial and ultrastructural changes in hemopoietic cells.", "content": "Bone marrow from a patient with bilateral staphylococcal bronchopneumonia who was treated with large doses of chloramphenicol was examined with the electron microscope. Our study supports the currently accepted concept that this drug depresses protein synthesis in mitochondria as it does in bacteria, since numerous alterations of mitochondrial morphology were encountered. These include (1) swollen mitochondria; (2) mitochondria with ruptured envelope; (3) mitochondria with longitudinally oriented cristae; (4) \"ring\" mitochondria; and (5) mitochondria with intramatrical iron deposits. The electron microscopical study discloses that the well documented vacuoles seen in marrow cells on light microscopy after treatment with this drug represent lipid droplets.", "contents": "Chloramphenicol-induced mitochondrial and ultrastructural changes in hemopoietic cells. Bone marrow from a patient with bilateral staphylococcal bronchopneumonia who was treated with large doses of chloramphenicol was examined with the electron microscope. Our study supports the currently accepted concept that this drug depresses protein synthesis in mitochondria as it does in bacteria, since numerous alterations of mitochondrial morphology were encountered. These include (1) swollen mitochondria; (2) mitochondria with ruptured envelope; (3) mitochondria with longitudinally oriented cristae; (4) \"ring\" mitochondria; and (5) mitochondria with intramatrical iron deposits. The electron microscopical study discloses that the well documented vacuoles seen in marrow cells on light microscopy after treatment with this drug represent lipid droplets."}
{"id": "PMID:185987", "title": "Cytomegalovirus infection of the female genital tract. Histologic findings in three cases and review of the literature.", "content": "Three cases of cytomegalovirus infection of the female genital tract, diagnosed on curettage, revealed a characteristic, although nonspecific histologic picture. This consisted of dense lymphocytic and plasma cell infiltrates with lymphoid follicles and signs of rapid cell turnover in the cervix when the latter was affected. The characteristic inclusions were very scant or even absent. The symptoms were not of diagnostic value.", "contents": "Cytomegalovirus infection of the female genital tract. Histologic findings in three cases and review of the literature. Three cases of cytomegalovirus infection of the female genital tract, diagnosed on curettage, revealed a characteristic, although nonspecific histologic picture. This consisted of dense lymphocytic and plasma cell infiltrates with lymphoid follicles and signs of rapid cell turnover in the cervix when the latter was affected. The characteristic inclusions were very scant or even absent. The symptoms were not of diagnostic value."}
{"id": "PMID:185988", "title": "[Changes in the activity of the supraoptic nuclei of the hypothalamus and distal portions of the hypothalamo-hypophyseal neurosecretory system of guinea pigs under the influence of high environmental temperature].", "content": "The keeping of guinea pigs in a thermochamber at 37 degrees C for 3 days resulted in increased releasing of neurohormones of the posterior lobe of the hypophysis. By the end of the 3d day there was no substantial difference between the average logarhythm of the volume of cell nuclei of the supraoptic nucleus of experimental animals and that of intact animals. Injection of ACTH after a preliminary three-day presence of the animal in the thermochamber caused a pronounced inhibition of the hypothalamo-hypophyseal neurosecretory system (HHNS). The HHNS of animals subjected to 3-day-long continuous exposure to high temperature, in contrast to the HHNS of intact animals is not capable to increase its activity in responses to stress (immobilization).", "contents": "[Changes in the activity of the supraoptic nuclei of the hypothalamus and distal portions of the hypothalamo-hypophyseal neurosecretory system of guinea pigs under the influence of high environmental temperature]. The keeping of guinea pigs in a thermochamber at 37 degrees C for 3 days resulted in increased releasing of neurohormones of the posterior lobe of the hypophysis. By the end of the 3d day there was no substantial difference between the average logarhythm of the volume of cell nuclei of the supraoptic nucleus of experimental animals and that of intact animals. Injection of ACTH after a preliminary three-day presence of the animal in the thermochamber caused a pronounced inhibition of the hypothalamo-hypophyseal neurosecretory system (HHNS). The HHNS of animals subjected to 3-day-long continuous exposure to high temperature, in contrast to the HHNS of intact animals is not capable to increase its activity in responses to stress (immobilization)."}
{"id": "PMID:185990", "title": "Acromutilating, paralyzing neuropathy with corneal ulceration in Navajo children.", "content": "Four Navajo children had a mutilating neuropathy with severe motor involvement. The disorder appears to be recessively inherited and is present from the earliest observable age. Manifestations include severe anesthesia, corneal ulceration, painless fractures, acral mutilation, and weakness. Mental function is normal. Sural nerves are practically devoid of myelinated fibers that show no evidence of regeneration. Unmyelinated axons show degenerative and regenerative morphologic and histometric features. Onion bulb formation is absent. We believe this neuropathy is a distinct clinical entity.", "contents": "Acromutilating, paralyzing neuropathy with corneal ulceration in Navajo children. Four Navajo children had a mutilating neuropathy with severe motor involvement. The disorder appears to be recessively inherited and is present from the earliest observable age. Manifestations include severe anesthesia, corneal ulceration, painless fractures, acral mutilation, and weakness. Mental function is normal. Sural nerves are practically devoid of myelinated fibers that show no evidence of regeneration. Unmyelinated axons show degenerative and regenerative morphologic and histometric features. Onion bulb formation is absent. We believe this neuropathy is a distinct clinical entity."}
{"id": "PMID:185991", "title": "Single-agent chemotherapy of brain tumors. A five-year review.", "content": "Identification of effective single chemotherapeutic agents for brain tumors must precede the rational use of multiple drug combinations. In phase 2 trials beginning in 1968, 158 patients with intrinsic brain tumors (mostly recurrent malignant astrocytomas) were considered evaluable. The larger trials with more effective drugs produced these results: carmustine (BCNU) response rate, 47%, with median duration of nine months; lomustine (CCNU), 44%, with median duration of six months; procarbazine hydrochloride, 52%, with median duration six months; carmustine and vincristine sulfate combined, 44%, with median duration of only four months; and BIC (5-[3,3-bis(2-chloroethyl)-1-triazeno]imidazole-4-carboxamide), 38%, with median duration of five months. Administration of glucocorticoids was not found to bias the frequency of response. Forty-seven patients, 26 of whom had responded to the initial drug, received a second drug. Among 26 patients who were evaluable, only four responded to the second drug.", "contents": "Single-agent chemotherapy of brain tumors. A five-year review. Identification of effective single chemotherapeutic agents for brain tumors must precede the rational use of multiple drug combinations. In phase 2 trials beginning in 1968, 158 patients with intrinsic brain tumors (mostly recurrent malignant astrocytomas) were considered evaluable. The larger trials with more effective drugs produced these results: carmustine (BCNU) response rate, 47%, with median duration of nine months; lomustine (CCNU), 44%, with median duration of six months; procarbazine hydrochloride, 52%, with median duration six months; carmustine and vincristine sulfate combined, 44%, with median duration of only four months; and BIC (5-[3,3-bis(2-chloroethyl)-1-triazeno]imidazole-4-carboxamide), 38%, with median duration of five months. Administration of glucocorticoids was not found to bias the frequency of response. Forty-seven patients, 26 of whom had responded to the initial drug, received a second drug. Among 26 patients who were evaluable, only four responded to the second drug."}
{"id": "PMID:185992", "title": "Extrajunctional acetylcholine receptors. Alterations in human and experimental neuromuscular diseases.", "content": "Diffuse extrajunctional acethycholine receptors (AChR) of skeletal muscle fibers were readily visualized by light and electron microscopy in muscle biopsy specimens of experimental denervation and human denervating diseases by use of an alpha-bungarotoxin immunoperoxidase technique. In peripheral neuropathies and various motor neuron diseases, a significant number of muscle fibers appearing denervated by histochemical criteria have diffuse extrajunctional AChR like those experimentally denervated by cutting the motor nerve supply. In portions of muscle fibers experimentally deprived of neuronal influence by direct injury, diffuse extrajunctional AChR developed, demonstrating that a denervation-like diffuse appearance of extrajunctional AChR can develop other than with neuronal damage, ie, it can be myogenous. Similar extrajunctional AChR was seen in some regenerating fibers of human myopathies, especially inflammatory myopathies.", "contents": "Extrajunctional acetylcholine receptors. Alterations in human and experimental neuromuscular diseases. Diffuse extrajunctional acethycholine receptors (AChR) of skeletal muscle fibers were readily visualized by light and electron microscopy in muscle biopsy specimens of experimental denervation and human denervating diseases by use of an alpha-bungarotoxin immunoperoxidase technique. In peripheral neuropathies and various motor neuron diseases, a significant number of muscle fibers appearing denervated by histochemical criteria have diffuse extrajunctional AChR like those experimentally denervated by cutting the motor nerve supply. In portions of muscle fibers experimentally deprived of neuronal influence by direct injury, diffuse extrajunctional AChR developed, demonstrating that a denervation-like diffuse appearance of extrajunctional AChR can develop other than with neuronal damage, ie, it can be myogenous. Similar extrajunctional AChR was seen in some regenerating fibers of human myopathies, especially inflammatory myopathies."}
{"id": "PMID:185995", "title": "Quantitation of bacterial infection and antibiotic effect in the cornea.", "content": "We report an experimental model that allows objective quantitation of bacterial keratitis. The model permits direct measurement of the number of viable organisms in the cornea after varying periods of in vivo growth. The size of the inoculum used to produce the corneal infection is critical, and the experimental organism must be standardized for its growth characteristics in the cornea. The end point is an objective one, productive of numerical data that can be subjected to statistical analysis. The findings are highly reproducible and the system is sufficiently sensitive to indicate the ability of a topically administered antibiotic to reduce the number of viable organisms in the cornea of an outbred rabbit population.", "contents": "Quantitation of bacterial infection and antibiotic effect in the cornea. We report an experimental model that allows objective quantitation of bacterial keratitis. The model permits direct measurement of the number of viable organisms in the cornea after varying periods of in vivo growth. The size of the inoculum used to produce the corneal infection is critical, and the experimental organism must be standardized for its growth characteristics in the cornea. The end point is an objective one, productive of numerical data that can be subjected to statistical analysis. The findings are highly reproducible and the system is sufficiently sensitive to indicate the ability of a topically administered antibiotic to reduce the number of viable organisms in the cornea of an outbred rabbit population."}
{"id": "PMID:185996", "title": "Bilateral asynchronous mixed tumors of the parotid gland.", "content": "Bilateral occurrence of benign mixed tumors of the salivary glands is rare. Simultaneous involvement of the submandibular and parotid glands has been described. Multicentric foci in the parotid gland has also been reported. Only four cases of bilateral mixed tumors, occurring simultaneously and confined to the parotid glands, have been reported. We report the first known cases of bilateral asynchronous benign mixed tumors of the parotid and review the pertinent literature.", "contents": "Bilateral asynchronous mixed tumors of the parotid gland. Bilateral occurrence of benign mixed tumors of the salivary glands is rare. Simultaneous involvement of the submandibular and parotid glands has been described. Multicentric foci in the parotid gland has also been reported. Only four cases of bilateral mixed tumors, occurring simultaneously and confined to the parotid glands, have been reported. We report the first known cases of bilateral asynchronous benign mixed tumors of the parotid and review the pertinent literature."}
{"id": "PMID:185998", "title": "A community dental health project. I. Self applied SnF2-ZrSiO4 prophylactic paste and dental caries in primary school children.", "content": "A dental health programme which employed group self prophylaxis by school children aged 5-9 years is described. The group used 10 per cent SnF2-ZrSiO4 paste and was supervised within the school by an auxiliary of parents under the direction of a dentist. There was a 36 per cent reduction in DMFT increment at the end of two years in the children aged 7-9 years.", "contents": "A community dental health project. I. Self applied SnF2-ZrSiO4 prophylactic paste and dental caries in primary school children. A dental health programme which employed group self prophylaxis by school children aged 5-9 years is described. The group used 10 per cent SnF2-ZrSiO4 paste and was supervised within the school by an auxiliary of parents under the direction of a dentist. There was a 36 per cent reduction in DMFT increment at the end of two years in the children aged 7-9 years."}
{"id": "PMID:185999", "title": "A mucosal disease virus as a cause of abortion hairy birth coat and unthriftiness in sheep. 1. Infiction of pregnant ewes and observations on aborted foetuses and lambs dying before one week of age.", "content": "A condition resembling border disease has been transmitted by the inoculation of pregnant ewes with material from affected lambs. Forty-nine merino ewes, mated to merino rams 7 to 87 days previously, were inoculated with an homogenate of brain, spinal cord and spleen from affected lambs. Mummified foetuses, abortions and stillbirths were observed, and lambs with hairy birth coats were born to ewes inoculated between days 12 to 70 of gestation. A mucosal disease virus (MDV), present in the original material, was recovered from the aborted foetuses and lambs. Attempts to induce passive protection using bovine anti-serum to the C24V strain of MDV were not successful. The condition was also transmitted by inoculation of pregnant ewes with a cell culture supernatant prepared from tissue cultures that had been inoculated with an organ homogenate pool. MDV was present in the supernatant and was recovered from aborted foetuses and lambs. It is suggested that a condition in sheep in Australia resembling border disease is due to the infection of the pregnant ewe by a mucosal disease virus.", "contents": "A mucosal disease virus as a cause of abortion hairy birth coat and unthriftiness in sheep. 1. Infiction of pregnant ewes and observations on aborted foetuses and lambs dying before one week of age. A condition resembling border disease has been transmitted by the inoculation of pregnant ewes with material from affected lambs. Forty-nine merino ewes, mated to merino rams 7 to 87 days previously, were inoculated with an homogenate of brain, spinal cord and spleen from affected lambs. Mummified foetuses, abortions and stillbirths were observed, and lambs with hairy birth coats were born to ewes inoculated between days 12 to 70 of gestation. A mucosal disease virus (MDV), present in the original material, was recovered from the aborted foetuses and lambs. Attempts to induce passive protection using bovine anti-serum to the C24V strain of MDV were not successful. The condition was also transmitted by inoculation of pregnant ewes with a cell culture supernatant prepared from tissue cultures that had been inoculated with an organ homogenate pool. MDV was present in the supernatant and was recovered from aborted foetuses and lambs. It is suggested that a condition in sheep in Australia resembling border disease is due to the infection of the pregnant ewe by a mucosal disease virus."}
{"id": "PMID:186000", "title": "A mucosal disease virus as a cause of abortion, hairy birth coat and unthriftiness in sheep. 2. Observations on lambs surviving for longer than seven days.", "content": "A condition in Australian sheep resembling border disease was transmitted by the inoculation of pregnant ewes with material from affected lambs. This material contained mucosal disease virus (MDV). Twenty-two lambs comprising 6 from uninoculated control ewes, together with 11 with hairy coats and 5 with normal coats from inoculated ewes, were observed from 7 to 182 days after birth. Nine of the lambs from inoculated ewes died during the experiment from a variety of causes. Glial cell abnormalities were observed in control and affected lambs, but only 4 of the 11 hairy lambs were judged to have abnormal glial cells. There were no consistent histopathological findings indicative of MDV infection. MDV was recovered from tissues of all 11 hairy lambs, but not from any of the lambs with normal coats. The hairy lambs appeared to be immunologically tolerant to the virus. Susceptible sheep in contact with the hairy lambs were infected with MDV. It is suggested that a condition in Australian lambs characterised by hairiness of the birth coat and poor viability is due to foetal infection with a mucosal disease virus.", "contents": "A mucosal disease virus as a cause of abortion, hairy birth coat and unthriftiness in sheep. 2. Observations on lambs surviving for longer than seven days. A condition in Australian sheep resembling border disease was transmitted by the inoculation of pregnant ewes with material from affected lambs. This material contained mucosal disease virus (MDV). Twenty-two lambs comprising 6 from uninoculated control ewes, together with 11 with hairy coats and 5 with normal coats from inoculated ewes, were observed from 7 to 182 days after birth. Nine of the lambs from inoculated ewes died during the experiment from a variety of causes. Glial cell abnormalities were observed in control and affected lambs, but only 4 of the 11 hairy lambs were judged to have abnormal glial cells. There were no consistent histopathological findings indicative of MDV infection. MDV was recovered from tissues of all 11 hairy lambs, but not from any of the lambs with normal coats. The hairy lambs appeared to be immunologically tolerant to the virus. Susceptible sheep in contact with the hairy lambs were infected with MDV. It is suggested that a condition in Australian lambs characterised by hairiness of the birth coat and poor viability is due to foetal infection with a mucosal disease virus."}
{"id": "PMID:186001", "title": "The histopathology of infectious bronchitis in fowls infected with a nephrotropic \"T\" strain of virus.", "content": "The histopathology of the infectious bronchitis caused by the Cumming \"T\" strain of virus is described in fowls exposed to infection by an aerosol method. Desquamation of the ciliated and glandular epithelium throughout the trachea was seen 24 hours after exposure to virus. This was followed by rapid proliferation presumably of residual basal cells with the production of a stratified undifferentiated epithelial covering. Small areas of the tracheal submucosa showed lymphocytic infiltration by the 4th day. Cilia were first observed in the regenerating epithelium on the 7th day when mucous cells were also seen to be numerous. Alveolar mucous glands developed over the following 4 days and by the 12th day regeneration appeared complete. Pulmonary lesions were generally not severe and the air sacs were only slightly oedematous for 4 days following exposure. Necrosis of a few tubules scattered throughout the kidneys was seen on the 4th day. By the 6th day cystic tubules containing epithelial debris and polymorphonuclear leukocytes were prominent in both cortex and medulla and necrotic tubules were scattered throughout the kidneys. PAS positive granules were present in the renal tubular epithelium and were most pronounced in the distal convoluted tubules. Infiltration of the interstitium by lymphocytes and plasma cells was generally marked on the 7th day. The cytoplasm of these plasma cells was strongly PAS positive and such cells were most numerous on the 12th and 13th days after exposure and then their numbers rapidly declined. Regeneration of tubular epithelium was advanced by the 10th day and much of the cell debris had been cleared from the lumina of the tubules. What appeared to be compressed areas were seen in the cortex from the 13th day where glomeruli and tubules were numerous through considerably reduced in size. These were not seen after the 35th day, however an occasional lymph nodule persisted in the intersitium.", "contents": "The histopathology of infectious bronchitis in fowls infected with a nephrotropic \"T\" strain of virus. The histopathology of the infectious bronchitis caused by the Cumming \"T\" strain of virus is described in fowls exposed to infection by an aerosol method. Desquamation of the ciliated and glandular epithelium throughout the trachea was seen 24 hours after exposure to virus. This was followed by rapid proliferation presumably of residual basal cells with the production of a stratified undifferentiated epithelial covering. Small areas of the tracheal submucosa showed lymphocytic infiltration by the 4th day. Cilia were first observed in the regenerating epithelium on the 7th day when mucous cells were also seen to be numerous. Alveolar mucous glands developed over the following 4 days and by the 12th day regeneration appeared complete. Pulmonary lesions were generally not severe and the air sacs were only slightly oedematous for 4 days following exposure. Necrosis of a few tubules scattered throughout the kidneys was seen on the 4th day. By the 6th day cystic tubules containing epithelial debris and polymorphonuclear leukocytes were prominent in both cortex and medulla and necrotic tubules were scattered throughout the kidneys. PAS positive granules were present in the renal tubular epithelium and were most pronounced in the distal convoluted tubules. Infiltration of the interstitium by lymphocytes and plasma cells was generally marked on the 7th day. The cytoplasm of these plasma cells was strongly PAS positive and such cells were most numerous on the 12th and 13th days after exposure and then their numbers rapidly declined. Regeneration of tubular epithelium was advanced by the 10th day and much of the cell debris had been cleared from the lumina of the tubules. What appeared to be compressed areas were seen in the cortex from the 13th day where glomeruli and tubules were numerous through considerably reduced in size. These were not seen after the 35th day, however an occasional lymph nodule persisted in the intersitium."}
{"id": "PMID:186002", "title": "Encephalolopathies in cattle in Tasmania.", "content": "Five central nervous diseases are described and their relationships to previously recorded conditions are discussed. The conditions are congenital inclusion-body encephalopathy probably caused by a paramyxovirus infection, idiopathic neuraxial oedema of a newborn calf, focal symmetrical encephalomalacia of a young calf, yacca (Xanthorrhoea spp) poisoning of adult cattle leading to spinal demyelination, and focal demyelination and neuropathy in an adult cow.", "contents": "Encephalolopathies in cattle in Tasmania. Five central nervous diseases are described and their relationships to previously recorded conditions are discussed. The conditions are congenital inclusion-body encephalopathy probably caused by a paramyxovirus infection, idiopathic neuraxial oedema of a newborn calf, focal symmetrical encephalomalacia of a young calf, yacca (Xanthorrhoea spp) poisoning of adult cattle leading to spinal demyelination, and focal demyelination and neuropathy in an adult cow."}
{"id": "PMID:186003", "title": "Equine herpesviruses: type 3 as an abortigenic agent.", "content": "The inoculation of equine herpesvirus type 3 (EHV3) strain 65/61 into the amniotic cavity of a mare 6-7 months pregnant resulted in abortion 11 days later. Following abortion typical lesions of coital exanthema were not observed in the genital tract of the mare, nor was EHV3 isolated from her. Serological evidence, however, indicated that the mare was infected with EHV3 following inoculation. Grossly the foetal disease was characterised by placentitis, focal ulcerative dermatitis, focal necrosis of the lungs and a striking diptheritic gastritis. Histological findings were interstitial pneumonia, diffuse hepatitis, generalised myositis, extensive vascular necrosis and degeneration of a range of epithelial cells. EHV3 was isolated from the placenta and placental fluids, stomach fluid, pooled thoracic and abdominal fluid, skin, lung, spleen and small intestine of the foetus.", "contents": "Equine herpesviruses: type 3 as an abortigenic agent. The inoculation of equine herpesvirus type 3 (EHV3) strain 65/61 into the amniotic cavity of a mare 6-7 months pregnant resulted in abortion 11 days later. Following abortion typical lesions of coital exanthema were not observed in the genital tract of the mare, nor was EHV3 isolated from her. Serological evidence, however, indicated that the mare was infected with EHV3 following inoculation. Grossly the foetal disease was characterised by placentitis, focal ulcerative dermatitis, focal necrosis of the lungs and a striking diptheritic gastritis. Histological findings were interstitial pneumonia, diffuse hepatitis, generalised myositis, extensive vascular necrosis and degeneration of a range of epithelial cells. EHV3 was isolated from the placenta and placental fluids, stomach fluid, pooled thoracic and abdominal fluid, skin, lung, spleen and small intestine of the foetus."}
{"id": "PMID:186004", "title": "The immunisation of chickens against infectious avian encephalomyelitis.", "content": "An immune response was induced in chickens vaccinated with the NSW-1 virus by the intramuscular, eye drop, wing web or oral methods. The oral procedure was the most sensitive in inducing an immune response with the lowest dose of virus. The wing web method was the least sensitive. Clinical IAE developed in 1 chicken following intramuscular vaccination. The virus was recovered from the faeces of chickens vaccinated orally with 700 CID50 of the virus from the third to the tenth day after vaccination.", "contents": "The immunisation of chickens against infectious avian encephalomyelitis. An immune response was induced in chickens vaccinated with the NSW-1 virus by the intramuscular, eye drop, wing web or oral methods. The oral procedure was the most sensitive in inducing an immune response with the lowest dose of virus. The wing web method was the least sensitive. Clinical IAE developed in 1 chicken following intramuscular vaccination. The virus was recovered from the faeces of chickens vaccinated orally with 700 CID50 of the virus from the third to the tenth day after vaccination."}
{"id": "PMID:186005", "title": "Histopathology of fasting and bluecomb disease in turkey poults and embryos experimentally infected with bluecomb disease coronavirus.", "content": "The histopathology of fasting and bluecomb disease in one-day-old turkey poults inoculated with bluecomb disease coronavirus (BCDCV) was studied. Uninoculated fasting poults produced clinical signs similar to those observed in BCDCV-inoculated poults. No histological changes in the intestines were observed in the fasted poults whereas definite lesions were observed in the BCDCV-inoculated poults. The lesions did not differ significantly with whether they were fed or fasted. The severity of the lesions in the intestinal epithelium was in decreasing order in the jejunum, ileum, and cecum. The lesions first appeared 24 hours postinoculation (PI) and progressed through 96 hours PI, as marked shortening of the villi, loss of microvilli, granular appearance of the cytoplasm of epithelial cells with nuclear margination of chromatin, and accentuation of the nucleolus. Similar lesions were observed in the jejunum, ileum, and cecum of turkey embryos inoculated at 24 days old as well as poults from these embryos. Signs of healing were first seen at 120 hours PI. No histopathological changes were observed in the pancreas, brain, kidneys, liver, adrenal, and bursa of Fabricius. The intestinal lesions observed should be a useful histological technique for differentiating fasting from bluecomb disease in turkey poults.", "contents": "Histopathology of fasting and bluecomb disease in turkey poults and embryos experimentally infected with bluecomb disease coronavirus. The histopathology of fasting and bluecomb disease in one-day-old turkey poults inoculated with bluecomb disease coronavirus (BCDCV) was studied. Uninoculated fasting poults produced clinical signs similar to those observed in BCDCV-inoculated poults. No histological changes in the intestines were observed in the fasted poults whereas definite lesions were observed in the BCDCV-inoculated poults. The lesions did not differ significantly with whether they were fed or fasted. The severity of the lesions in the intestinal epithelium was in decreasing order in the jejunum, ileum, and cecum. The lesions first appeared 24 hours postinoculation (PI) and progressed through 96 hours PI, as marked shortening of the villi, loss of microvilli, granular appearance of the cytoplasm of epithelial cells with nuclear margination of chromatin, and accentuation of the nucleolus. Similar lesions were observed in the jejunum, ileum, and cecum of turkey embryos inoculated at 24 days old as well as poults from these embryos. Signs of healing were first seen at 120 hours PI. No histopathological changes were observed in the pancreas, brain, kidneys, liver, adrenal, and bursa of Fabricius. The intestinal lesions observed should be a useful histological technique for differentiating fasting from bluecomb disease in turkey poults."}
{"id": "PMID:186006", "title": "Infectious tenosynovitis (viral arthritis): influence of maternal antibodies on the development of tenosynovitis lesions after experimental infection by day-old chickens with tenosynovitis virus.", "content": "When chicks with maternal antibodies against infectious tenosynovitis (viral arthritis) virus were inoculated orally at 1 day old with tenosynovitis virus, they were protected against developing active tenosynovitis lesions 3 weeks later. They were not protected against subcutaneous inoculation, however. Breeder vaccination against tenosynovitis resulted in immunity of the progeny against oral infection at 1 day old, whereas progeny from unvaccinated breeders were susceptible to such a challenge.", "contents": "Infectious tenosynovitis (viral arthritis): influence of maternal antibodies on the development of tenosynovitis lesions after experimental infection by day-old chickens with tenosynovitis virus. When chicks with maternal antibodies against infectious tenosynovitis (viral arthritis) virus were inoculated orally at 1 day old with tenosynovitis virus, they were protected against developing active tenosynovitis lesions 3 weeks later. They were not protected against subcutaneous inoculation, however. Breeder vaccination against tenosynovitis resulted in immunity of the progeny against oral infection at 1 day old, whereas progeny from unvaccinated breeders were susceptible to such a challenge."}
{"id": "PMID:186007", "title": "A technique for isolating turkey respiratory adenoviruses.", "content": "Several turkey respiratory adenoviruses were isolated in turkey embryonic liver cells from nasal turbinate filtrate collected from clinically ill turkey poults during postmortem examination. Suspect adenovirus inoculum had to remain in cell culture for 5 to 7 days, and 9 blind passages were required before a sample was declared negative. Once isolated, the turkey adenoviruses adapted rapidly to turkey kidney cells.", "contents": "A technique for isolating turkey respiratory adenoviruses. Several turkey respiratory adenoviruses were isolated in turkey embryonic liver cells from nasal turbinate filtrate collected from clinically ill turkey poults during postmortem examination. Suspect adenovirus inoculum had to remain in cell culture for 5 to 7 days, and 9 blind passages were required before a sample was declared negative. Once isolated, the turkey adenoviruses adapted rapidly to turkey kidney cells."}
{"id": "PMID:186008", "title": "Turkey herpesvirus infection in chickens: induction of lymphoproliferative lesions and characterization of vaccinal immunity against Marek's disease.", "content": "Chickens vaccinated at hatching with high doses of turkey herpesvirus (HVT) developed viremia that peaked in titer around the 12th day and gradually declined. HVT infection also induced mild microscopic lymphoproliferative lesions in the nerves and gonads. These lesions were most prominent around the 12th day and then regressed. The fact that such lesions were also induced by HVT in cyclophosphamide-treated chicks suggests that they were T-cell-dependent. Some of the cells in early HVT lesions appeared to have morphologic properties of neoplastic cells. HVT viremia and lesions were both dose-dependent and were less in chickens with maternal antibodies against Marek's disease virus (MDV). Sequential studies on chickens vaccinated with HVT and challenged with MDV showed that chickens were protected against the earliest detectable MD viremia and lymphoproliferative lesion response attributed to MD. Also, the transient necrobiotic lesions associated with productive infection of thymic lymphocytes by MDV were totally absent in vaccinated chickens. These data provide further insight on the mechanisms by which HVT protects against MD lymphoma induction. A limited oncogenic (transforming) potential of HVT as suggested by our data would provide the basis to assume that at least one component of HVT-induced immunity may be directed against tumor-specific antigens. On the other hand, our observations that HVT protects against productive MDV infection in the thymus and against cell-associated viremia are evidence for an anti-viral immune response. These hypotheses are not mutually exclusive.", "contents": "Turkey herpesvirus infection in chickens: induction of lymphoproliferative lesions and characterization of vaccinal immunity against Marek's disease. Chickens vaccinated at hatching with high doses of turkey herpesvirus (HVT) developed viremia that peaked in titer around the 12th day and gradually declined. HVT infection also induced mild microscopic lymphoproliferative lesions in the nerves and gonads. These lesions were most prominent around the 12th day and then regressed. The fact that such lesions were also induced by HVT in cyclophosphamide-treated chicks suggests that they were T-cell-dependent. Some of the cells in early HVT lesions appeared to have morphologic properties of neoplastic cells. HVT viremia and lesions were both dose-dependent and were less in chickens with maternal antibodies against Marek's disease virus (MDV). Sequential studies on chickens vaccinated with HVT and challenged with MDV showed that chickens were protected against the earliest detectable MD viremia and lymphoproliferative lesion response attributed to MD. Also, the transient necrobiotic lesions associated with productive infection of thymic lymphocytes by MDV were totally absent in vaccinated chickens. These data provide further insight on the mechanisms by which HVT protects against MD lymphoma induction. A limited oncogenic (transforming) potential of HVT as suggested by our data would provide the basis to assume that at least one component of HVT-induced immunity may be directed against tumor-specific antigens. On the other hand, our observations that HVT protects against productive MDV infection in the thymus and against cell-associated viremia are evidence for an anti-viral immune response. These hypotheses are not mutually exclusive."}
{"id": "PMID:186009", "title": "Some properties of avian adenoviruses isolated from chickens with inclusion body hepatitis in Japan.", "content": "Outbreaks of inclusion body hepatitis were observed in broiler chickens on a poultry farm during 3 years. Avian adenovirus-like agents were isolated during these years from livers of diseased chickens. Round-cell-type cytopathogenic effect and intranuclear inclusion bodies were produced in chicken kidney cell cultures inoculated with these agents. Properties of the agents were as follows: resistant to ether, chloroform, socium deoxycholate, trypsin, heating at 50 C, and pH 3.0; sensitive to 5-iodo-deoxyuridine; and pathogenic to chicken embryos. From these properties and ultrastructural findings of the agents, these were identified as avian adenovirus. Day-old commercial chicks were insusceptible to these viruses. Maternal antibody levels in commercial chicks were considerable. Surveys for neutralizing index to the virus were performed on chickens in the field, and all sera tested were positive. Electron-microscope examination showed that these viruses contained avian-adenovirus-associated virus.", "contents": "Some properties of avian adenoviruses isolated from chickens with inclusion body hepatitis in Japan. Outbreaks of inclusion body hepatitis were observed in broiler chickens on a poultry farm during 3 years. Avian adenovirus-like agents were isolated during these years from livers of diseased chickens. Round-cell-type cytopathogenic effect and intranuclear inclusion bodies were produced in chicken kidney cell cultures inoculated with these agents. Properties of the agents were as follows: resistant to ether, chloroform, socium deoxycholate, trypsin, heating at 50 C, and pH 3.0; sensitive to 5-iodo-deoxyuridine; and pathogenic to chicken embryos. From these properties and ultrastructural findings of the agents, these were identified as avian adenovirus. Day-old commercial chicks were insusceptible to these viruses. Maternal antibody levels in commercial chicks were considerable. Surveys for neutralizing index to the virus were performed on chickens in the field, and all sera tested were positive. Electron-microscope examination showed that these viruses contained avian-adenovirus-associated virus."}
{"id": "PMID:186010", "title": "An adenovirus from a turkey pathogenic to both chicks and turkey poults.", "content": "An adenovirus, designated T-75 isolant, was isolated from the cloacal swab of a clinically normal turkey, 13 weeks old. The T-75 isolant was identified as an adenovirus on the basis of physicochemical properties, cytopathology, and agar-gel precipitin test. Producing two-way cross-neutralization reactions with CELO virus, the isolant was classified as an avian adenovirus of serotype 1. The T-75 isolant was pathogenic to both chicks and turkey poults, causing hepatitis, respiratory disease, atrophy of the bursa of Fabricius, and/or growth depression of experimentally inoculated birds, varying with the host and route of inoculation.", "contents": "An adenovirus from a turkey pathogenic to both chicks and turkey poults. An adenovirus, designated T-75 isolant, was isolated from the cloacal swab of a clinically normal turkey, 13 weeks old. The T-75 isolant was identified as an adenovirus on the basis of physicochemical properties, cytopathology, and agar-gel precipitin test. Producing two-way cross-neutralization reactions with CELO virus, the isolant was classified as an avian adenovirus of serotype 1. The T-75 isolant was pathogenic to both chicks and turkey poults, causing hepatitis, respiratory disease, atrophy of the bursa of Fabricius, and/or growth depression of experimentally inoculated birds, varying with the host and route of inoculation."}
{"id": "PMID:186011", "title": "Studies on the etiology of lymphomas in turkeys: isolation of reticuloendotheliosis in virus.", "content": "Studies of tissues from 25 normal turkey flocks and of 15 selected turkey lymphoid tumors revealed no Marek's disease or lymphoid leukosis viruses, although reticuloendotheliosis viruses (REV) were isolated from 3 flocks (2 with a history of neoplastic disease). The REV isolates were culturally and antigenically similar to the prototype REV strain T but were of low pathogenicity. Attempts failed to transmit 6 lymphoid tumors of diverse origin by inoculation into 2 strains of recipient turkeys. These data support an etiological role for REV in some though not all forms of turkey neoplastic disease.", "contents": "Studies on the etiology of lymphomas in turkeys: isolation of reticuloendotheliosis in virus. Studies of tissues from 25 normal turkey flocks and of 15 selected turkey lymphoid tumors revealed no Marek's disease or lymphoid leukosis viruses, although reticuloendotheliosis viruses (REV) were isolated from 3 flocks (2 with a history of neoplastic disease). The REV isolates were culturally and antigenically similar to the prototype REV strain T but were of low pathogenicity. Attempts failed to transmit 6 lymphoid tumors of diverse origin by inoculation into 2 strains of recipient turkeys. These data support an etiological role for REV in some though not all forms of turkey neoplastic disease."}
{"id": "PMID:186012", "title": "Rapid diagnosis of some avian virus diseases.", "content": "Direct electron microscopy was used to identify virions of infectious laryngotracheitis in lysed tracheal cells and of fowlpox in scabs and exudates from natural cases. Rapid identification of avian adenovirus and infectious laryngotracheitis by gel diffusion was possible using antigens prepared by simple distilled-water lysis of infected cell cultures. Precipitin lines were often visible within 5 hours.", "contents": "Rapid diagnosis of some avian virus diseases. Direct electron microscopy was used to identify virions of infectious laryngotracheitis in lysed tracheal cells and of fowlpox in scabs and exudates from natural cases. Rapid identification of avian adenovirus and infectious laryngotracheitis by gel diffusion was possible using antigens prepared by simple distilled-water lysis of infected cell cultures. Precipitin lines were often visible within 5 hours."}
{"id": "PMID:186013", "title": "Demonstration of Eimeria tenella in bursa of Fabricius of chickens.", "content": "Coccidial life-cytle stages were detected in the bursa of Fabricius of broiler chickens inoculated with Eimeria tenella, whether or not the chickens had previously been infected with infectious bursal disease virus (IBDV). Chickens infected only with E. tenella had developing parasites in the lining epithelium, whereas chickens with both infections had gametocytes also in the epithelial cells surrounding numerous degenerating bursal cysts.", "contents": "Demonstration of Eimeria tenella in bursa of Fabricius of chickens. Coccidial life-cytle stages were detected in the bursa of Fabricius of broiler chickens inoculated with Eimeria tenella, whether or not the chickens had previously been infected with infectious bursal disease virus (IBDV). Chickens infected only with E. tenella had developing parasites in the lining epithelium, whereas chickens with both infections had gametocytes also in the epithelial cells surrounding numerous degenerating bursal cysts."}
{"id": "PMID:186014", "title": "Avian cell cultures grown in an open system (dishes) without CO2 incubator, and their use for virus cultivation.", "content": "An organic buffer, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), in a culture medium made it possible to culture chick embryo fibroblast (CEF), duck embryo fibroblast (DEF), and chick kidney (CK) cells in an open system (dishes) under incubation in a bacteriological incubator, requiring no CO2 incubation. CEF, DEF, and CK cells cultured with this system were suitable for cultivation of avain viruses such as Newcastle disease virus, CELO virus, Marek's disease virus, and turkey herpesvirus.", "contents": "Avian cell cultures grown in an open system (dishes) without CO2 incubator, and their use for virus cultivation. An organic buffer, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), in a culture medium made it possible to culture chick embryo fibroblast (CEF), duck embryo fibroblast (DEF), and chick kidney (CK) cells in an open system (dishes) under incubation in a bacteriological incubator, requiring no CO2 incubation. CEF, DEF, and CK cells cultured with this system were suitable for cultivation of avain viruses such as Newcastle disease virus, CELO virus, Marek's disease virus, and turkey herpesvirus."}
{"id": "PMID:186017", "title": "Cardiac output during human sleep.", "content": "Impedance cardiogram and sleep EEG were recorded from four male and four female subjects, aged 21 to 22 years, during one night in the laboratory following one adaptation night. Cardiac output fell approximately 26% during the night as a consequence of diminished stroke volume, the lowest values of both occurring during the latter portion of the night, dominated by SREM (rapid-eye-movement stage). Intracycle comparisons between SREM and SWS (slow wave sleep) or between eye movement burst and non-burst SREM showed no significant differences in stroke volume or cardiac output. Pre-ejection period and systolic ejection period were measured and discussed. The non-coincidence of the nadir of metabolic activity, expressed as cardiac output, and the apex of slow-wave sleep activity supported the concept of slow-wave sleep as a period of physiological restoration.", "contents": "Cardiac output during human sleep. Impedance cardiogram and sleep EEG were recorded from four male and four female subjects, aged 21 to 22 years, during one night in the laboratory following one adaptation night. Cardiac output fell approximately 26% during the night as a consequence of diminished stroke volume, the lowest values of both occurring during the latter portion of the night, dominated by SREM (rapid-eye-movement stage). Intracycle comparisons between SREM and SWS (slow wave sleep) or between eye movement burst and non-burst SREM showed no significant differences in stroke volume or cardiac output. Pre-ejection period and systolic ejection period were measured and discussed. The non-coincidence of the nadir of metabolic activity, expressed as cardiac output, and the apex of slow-wave sleep activity supported the concept of slow-wave sleep as a period of physiological restoration."}
{"id": "PMID:186015", "title": "Infectious tenosynovitis in commercial White Leghorn chickens.", "content": "Infectious tenosynovitis was diagnosed in three separate outbreaks in a commercial White Leghorn hens, though not previously reported in adult White Leghorns (3). Clinically affected flocks had decreased production and increased daily mortality, with many hens showing signs of the so called \"cage-fatigue bluecomb\" syndrome. Most sick birds had lesions typical of infectious tenosynovitis, with pronounced cyanosis and dehydration. Dead birds had signs of acute septicemia. The course of the disease (about 8 weeks) was not altered by the medicinal regimens tried. Young laying-age flocks were most seriously affected. Production losses averaged 15 to 20%, and mortality reached 5% per month during the recovery phase.", "contents": "Infectious tenosynovitis in commercial White Leghorn chickens. Infectious tenosynovitis was diagnosed in three separate outbreaks in a commercial White Leghorn hens, though not previously reported in adult White Leghorns (3). Clinically affected flocks had decreased production and increased daily mortality, with many hens showing signs of the so called \"cage-fatigue bluecomb\" syndrome. Most sick birds had lesions typical of infectious tenosynovitis, with pronounced cyanosis and dehydration. Dead birds had signs of acute septicemia. The course of the disease (about 8 weeks) was not altered by the medicinal regimens tried. Young laying-age flocks were most seriously affected. Production losses averaged 15 to 20%, and mortality reached 5% per month during the recovery phase."}
{"id": "PMID:186016", "title": "Clostridium perfringens infection in turkey poults.", "content": "Necropsy of dead and sick 5-day-old poults from a flock of 12,500 Broad-Breasted White turkeys having high early mortality (685 the first week) revealed rather large inflamed retained yolk sacs with semiliquid contents, ascites, and swollen greenish-colored livers. Cultures of livers and yolk sacs were negative by standard aerobic procedures for salmonella and any other bacterial pathogens. At the beginning of the 4th week, more poults were necropsied and found to have swollen livers with necrotic foci grossly visible, and a necrotic inflammation of the midintestinal tract extending anteriorly from attachment of the yolk stalk. Clostridium perfringens was isolated from livers and yolk remnants by anaerobic culture.", "contents": "Clostridium perfringens infection in turkey poults. Necropsy of dead and sick 5-day-old poults from a flock of 12,500 Broad-Breasted White turkeys having high early mortality (685 the first week) revealed rather large inflamed retained yolk sacs with semiliquid contents, ascites, and swollen greenish-colored livers. Cultures of livers and yolk sacs were negative by standard aerobic procedures for salmonella and any other bacterial pathogens. At the beginning of the 4th week, more poults were necropsied and found to have swollen livers with necrotic foci grossly visible, and a necrotic inflammation of the midintestinal tract extending anteriorly from attachment of the yolk stalk. Clostridium perfringens was isolated from livers and yolk remnants by anaerobic culture."}
{"id": "PMID:186019", "title": "Early carcinoma of the gallbladder.", "content": "The material consisted of 12 gallbladder carcinomas, all in their early phases. Ten of the patients were female, two were male. The mean age of the patients was 65 years, and the mean lifetime after operation was as short as five months. The purpose of this study was to obtain further information on the significance of metaplastic mucosal islands in the histogenesis of gallbladder carcinomas by investigating incipient carcinomas and the conditions of the adjacent mucosa. The investigation revealed goblet cells and enterochromaffin cells outside the tumour in four specimens, antral-type glands in ten specimens, gastric-type superficial epithelial islands in all twelve specimens. In eight cases there was an antral-type mucosal island outside the tumour. In six specimens the tumour was found to border on antral-type mucosa. The structure of the tumour was papillary in ten cases, and mucinous in two. The tumorous epithelium showed in all specimens focal intestinal-type areas. Six tumours displayed goblet cells, and enterochromaffin cells were present in four tumours. The two mucinous tumours seemed to have originated in the glands of the antral-type mucosa extending toward the serosal surface of the gallbladder wall. This study supports the theory suggesting a significance of metaplasia in the histogenesis of gallbladder tumours.", "contents": "Early carcinoma of the gallbladder. The material consisted of 12 gallbladder carcinomas, all in their early phases. Ten of the patients were female, two were male. The mean age of the patients was 65 years, and the mean lifetime after operation was as short as five months. The purpose of this study was to obtain further information on the significance of metaplastic mucosal islands in the histogenesis of gallbladder carcinomas by investigating incipient carcinomas and the conditions of the adjacent mucosa. The investigation revealed goblet cells and enterochromaffin cells outside the tumour in four specimens, antral-type glands in ten specimens, gastric-type superficial epithelial islands in all twelve specimens. In eight cases there was an antral-type mucosal island outside the tumour. In six specimens the tumour was found to border on antral-type mucosa. The structure of the tumour was papillary in ten cases, and mucinous in two. The tumorous epithelium showed in all specimens focal intestinal-type areas. Six tumours displayed goblet cells, and enterochromaffin cells were present in four tumours. The two mucinous tumours seemed to have originated in the glands of the antral-type mucosa extending toward the serosal surface of the gallbladder wall. This study supports the theory suggesting a significance of metaplasia in the histogenesis of gallbladder tumours."}
{"id": "PMID:186023", "title": "Electron microscopic observations of FL cells infected with herpes simplex virus. III. Dense bodies.", "content": "FL cells infected with the -GCr Miyama strain of herpes simplex virus at an adsorbed multiplicity of approximately 10 were fixed at late stages of infection and examined by electron microscopy. Dense bodies containing electron-dense material and surrounded by a limiting membrane were occasionally observed in the perinuclear disternae and in intranuclear vacuoles. Budding of electron-dense material to the cisternae with acquisition of a limiting membrane at the inner nuclear membrane was also occasionally observed. These findings are in constrast with observations that in cells infected with cytomegalovirus numerous dense bodies and their budding process were observed only in the cytoplasmic area.", "contents": "Electron microscopic observations of FL cells infected with herpes simplex virus. III. Dense bodies. FL cells infected with the -GCr Miyama strain of herpes simplex virus at an adsorbed multiplicity of approximately 10 were fixed at late stages of infection and examined by electron microscopy. Dense bodies containing electron-dense material and surrounded by a limiting membrane were occasionally observed in the perinuclear disternae and in intranuclear vacuoles. Budding of electron-dense material to the cisternae with acquisition of a limiting membrane at the inner nuclear membrane was also occasionally observed. These findings are in constrast with observations that in cells infected with cytomegalovirus numerous dense bodies and their budding process were observed only in the cytoplasmic area."}
{"id": "PMID:186024", "title": "Glk: a locus controlling galactokinase activity in the mouse.", "content": "Inbred strains of mice exhibited significant variation in whole blood galactokinase (GALK) activity. Activities tend to cluster into two classes, one class having approximately twice the activity of the other. Hybrids (F1) between \"high\" and \"low\" strains have activity intermediate between the parental activities. Two sets of recombinant inbred (RI) lines were developed by brother-sister mating, beginning with F2 generations of crosses between different pairs of high and low GALK activity strains. The RI lines segregated in terms of GALK activity, indicating single gene inheritance; this galactokinase locus has been designated Glk. The strain distribution patterns of both RI series agreed closely with esterase-3 (Es-3) alleles of the respective parental strains (31/34 independently derived strains were concordant for Es-3 and Glk genotypes), a finding consistent with a map distance between loci of 2.5 cM. Es-3 has been located on the distal end of chromosome 11. Glk, with its alleles Glka (lower activity) and Glkb (higher activity), is therefore assigned to the same region.", "contents": "Glk: a locus controlling galactokinase activity in the mouse. Inbred strains of mice exhibited significant variation in whole blood galactokinase (GALK) activity. Activities tend to cluster into two classes, one class having approximately twice the activity of the other. Hybrids (F1) between \"high\" and \"low\" strains have activity intermediate between the parental activities. Two sets of recombinant inbred (RI) lines were developed by brother-sister mating, beginning with F2 generations of crosses between different pairs of high and low GALK activity strains. The RI lines segregated in terms of GALK activity, indicating single gene inheritance; this galactokinase locus has been designated Glk. The strain distribution patterns of both RI series agreed closely with esterase-3 (Es-3) alleles of the respective parental strains (31/34 independently derived strains were concordant for Es-3 and Glk genotypes), a finding consistent with a map distance between loci of 2.5 cM. Es-3 has been located on the distal end of chromosome 11. Glk, with its alleles Glka (lower activity) and Glkb (higher activity), is therefore assigned to the same region."}
{"id": "PMID:186025", "title": "In vivo measurement of pyridine nucleotide fluorescence from cat brain cortex.", "content": "A modification of the methods is described which makes it possible to measure pyridine nucleotide fluorescence from the brain cortex in vivo without interference from movement and hemodynamic artifacts. Movement artifacts were eliminated by the use of a window technique. Fluorescence changes due to changes in hemoglobin oxygenation have been eliminated by measuring fluorescence at an isobestic wavelength of the hemoglobin-oxyhemoglobin reaction. The interference due to changes in red blood cell concentration has been studied by simultaneous measurements of fluorescence and ultraviolet reflection. Hemodilution revealed a linear relationship between the fluorescence from the pyridine nucleotide and reflected ultraviolet light. The ratio between the light absorption changes was approximately unity under the particular optical geometry employed in this study. This method has been used to measure fluorescence changes produced by nitrogen anoxia. The technique is discussed in relation to previous methods and the effects of anoxia are compared to previous findings.", "contents": "In vivo measurement of pyridine nucleotide fluorescence from cat brain cortex. A modification of the methods is described which makes it possible to measure pyridine nucleotide fluorescence from the brain cortex in vivo without interference from movement and hemodynamic artifacts. Movement artifacts were eliminated by the use of a window technique. Fluorescence changes due to changes in hemoglobin oxygenation have been eliminated by measuring fluorescence at an isobestic wavelength of the hemoglobin-oxyhemoglobin reaction. The interference due to changes in red blood cell concentration has been studied by simultaneous measurements of fluorescence and ultraviolet reflection. Hemodilution revealed a linear relationship between the fluorescence from the pyridine nucleotide and reflected ultraviolet light. The ratio between the light absorption changes was approximately unity under the particular optical geometry employed in this study. This method has been used to measure fluorescence changes produced by nitrogen anoxia. The technique is discussed in relation to previous methods and the effects of anoxia are compared to previous findings."}
{"id": "PMID:186026", "title": "Studies on partially reduced mammalian cytochrome oxidase reactions with ferrocytochrome c.", "content": "The kinetics of the electron-transfer process which occurs between ferrocytochrome c and partially reduced mammalian cytochrome oxidase were studied by the rapid spectrophotometric techniques of stopped flow and temperature jump. Stopped-flow experiments showed initial very fast extinction changes at 605 nm and at 563 nm, indicating the simultaneous reduction of cytochrome a and oxidation of ferrocytochrome c. During this 'burst' phase, say the first 50 ms after mixing, it was invariably found that more cytochrome c had been oxidized than cytochrome a had been reduced. This discrepancy in electron equivalents may be accounted for by the rapid reduction of another redox site in the enzyme, possibly that associated with the extinction changes observed at 830 nm. During the incubation period in which the partially reduced oxidase was prepared, the rate of reduction of cytochrome a by ferrocytochrome c, at constant reactant concentrations, decreased with time. Temperature-jump experiments showed the presence of two relaxation processes. The faster of the two phases was assigned to the electron-transfer reaction between cytochrome c and cytochrome a. A study of the concentration-dependence of the reciprocal relaxation time for this phase yielded a rate constant of 9 X 10(6)M-1-s-1 for the electron transfer from cytochrome c to cytochrome a, and a value of 8.5 X 10(6)M-1-s-1 for the reverse reaction. The equilibrium constant for the electron-transfer reaction is therefore close to unity. The slower phase has been interpreted as signalling the transfer of electrons between cytochrome a and another redox site within the oxidase molecule.", "contents": "Studies on partially reduced mammalian cytochrome oxidase reactions with ferrocytochrome c. The kinetics of the electron-transfer process which occurs between ferrocytochrome c and partially reduced mammalian cytochrome oxidase were studied by the rapid spectrophotometric techniques of stopped flow and temperature jump. Stopped-flow experiments showed initial very fast extinction changes at 605 nm and at 563 nm, indicating the simultaneous reduction of cytochrome a and oxidation of ferrocytochrome c. During this 'burst' phase, say the first 50 ms after mixing, it was invariably found that more cytochrome c had been oxidized than cytochrome a had been reduced. This discrepancy in electron equivalents may be accounted for by the rapid reduction of another redox site in the enzyme, possibly that associated with the extinction changes observed at 830 nm. During the incubation period in which the partially reduced oxidase was prepared, the rate of reduction of cytochrome a by ferrocytochrome c, at constant reactant concentrations, decreased with time. Temperature-jump experiments showed the presence of two relaxation processes. The faster of the two phases was assigned to the electron-transfer reaction between cytochrome c and cytochrome a. A study of the concentration-dependence of the reciprocal relaxation time for this phase yielded a rate constant of 9 X 10(6)M-1-s-1 for the electron transfer from cytochrome c to cytochrome a, and a value of 8.5 X 10(6)M-1-s-1 for the reverse reaction. The equilibrium constant for the electron-transfer reaction is therefore close to unity. The slower phase has been interpreted as signalling the transfer of electrons between cytochrome a and another redox site within the oxidase molecule."}
{"id": "PMID:186027", "title": "Modification of diamine oxidase activity in vitro by metabolites of asparagine and differences in asparagine decarboxylation in normal and virus-transformed baby hamster kidney cells.", "content": "1. The oxidation of putrescine in vitro by pig kidney diamine oxidase (EC 1.4.3.6) was increased in the presence of 2-oxosuccinamic acid and malonamic acid. 2. It was inhibited by 3-aminopropionamide, oxaloacetate and pyruvate. 3. 2-Oxosuccinamate was derived from asparagine in virus-transformed baby hamster kidney (BHK) cells growing in tissue culture. 4. Asparagine was decarboxylated more efficiently by transformed than by normal BHK cells. 5. In BHK cells transformed by polyoma virus (Py BHK), 2-oxosuccinamate is the most likely immediate precursor of the 14CO2 arising from [U-14C]asparagine, and there was some evidence for its formation in an asparagine-dependent clone of BHK cells before and after their transformation by hamster sarcoma virus (respectively Asn- and HSV Asn-). 6. The relationship between 2-oxosuccinamate and pyruvate and the possible roles of these two substances in controlling cellular diamine oxidase activity are discussed.", "contents": "Modification of diamine oxidase activity in vitro by metabolites of asparagine and differences in asparagine decarboxylation in normal and virus-transformed baby hamster kidney cells. 1. The oxidation of putrescine in vitro by pig kidney diamine oxidase (EC 1.4.3.6) was increased in the presence of 2-oxosuccinamic acid and malonamic acid. 2. It was inhibited by 3-aminopropionamide, oxaloacetate and pyruvate. 3. 2-Oxosuccinamate was derived from asparagine in virus-transformed baby hamster kidney (BHK) cells growing in tissue culture. 4. Asparagine was decarboxylated more efficiently by transformed than by normal BHK cells. 5. In BHK cells transformed by polyoma virus (Py BHK), 2-oxosuccinamate is the most likely immediate precursor of the 14CO2 arising from [U-14C]asparagine, and there was some evidence for its formation in an asparagine-dependent clone of BHK cells before and after their transformation by hamster sarcoma virus (respectively Asn- and HSV Asn-). 6. The relationship between 2-oxosuccinamate and pyruvate and the possible roles of these two substances in controlling cellular diamine oxidase activity are discussed."}
{"id": "PMID:186028", "title": "Isolation of membrane-bound renal enzymes that metabolize kinins and angiotensins.", "content": "Cortex of rat kidney was homogenized and fractions enriched in plasma membrane, endoplasmic reticulum or brush border were prepared by several techniques of differential centrifugation. The identity and homogeneity of the membrane fragments were investigated by assaying marker enzymes and by transmission and scanning electron microscopy. Kallikrein was present in both plasma-membrane- and endoplasmic-reticulum-enriched fractions isolated by two fractionation procedures. Kallikrein was highly concentrated in a plasma-membrane fraction but was absent from the brush-border membrane of proximal tubular cells. Cells of transplanted renal tumours of the rat, originating from the proximal tubule, had no kallikrein activity. Kininase activity, angiotensin I-converting enzyme (kininase II) and angiotensinase were found in a plasma-membrane-enriched fraction and especially in the fraction containing isolated brush border. It is suggested that after renal kallikrein is synthesized on endoplasmic reticulum, it is subsequently reoriented to a surface membrane for activation and release. Renal kallikrein may enter the tubular filtrate distal to the proximal tubules. The brush-border membrane of proximal tubule is the major site of inactivation of kinins and angiotensin II..", "contents": "Isolation of membrane-bound renal enzymes that metabolize kinins and angiotensins. Cortex of rat kidney was homogenized and fractions enriched in plasma membrane, endoplasmic reticulum or brush border were prepared by several techniques of differential centrifugation. The identity and homogeneity of the membrane fragments were investigated by assaying marker enzymes and by transmission and scanning electron microscopy. Kallikrein was present in both plasma-membrane- and endoplasmic-reticulum-enriched fractions isolated by two fractionation procedures. Kallikrein was highly concentrated in a plasma-membrane fraction but was absent from the brush-border membrane of proximal tubular cells. Cells of transplanted renal tumours of the rat, originating from the proximal tubule, had no kallikrein activity. Kininase activity, angiotensin I-converting enzyme (kininase II) and angiotensinase were found in a plasma-membrane-enriched fraction and especially in the fraction containing isolated brush border. It is suggested that after renal kallikrein is synthesized on endoplasmic reticulum, it is subsequently reoriented to a surface membrane for activation and release. Renal kallikrein may enter the tubular filtrate distal to the proximal tubules. The brush-border membrane of proximal tubule is the major site of inactivation of kinins and angiotensin II.."}
{"id": "PMID:186029", "title": "Phosphorylation of synaptic-membrane proteins from ox cerebral cortex in vitro. Partition of substrates and protein kinase activities with triton X-100.", "content": "Synaptic-membrane fragments from ox cerebral cortex contain basal and cyclic AMP-stimulated protein kinase activity catalysing the phosphorylation of endogenous substrates. Extraction of membrane fragments with Triton X-100 solubilized less than 20% of the kinase activity and left the major part of the endogenous substrates in the insoluble fraction.", "contents": "Phosphorylation of synaptic-membrane proteins from ox cerebral cortex in vitro. Partition of substrates and protein kinase activities with triton X-100. Synaptic-membrane fragments from ox cerebral cortex contain basal and cyclic AMP-stimulated protein kinase activity catalysing the phosphorylation of endogenous substrates. Extraction of membrane fragments with Triton X-100 solubilized less than 20% of the kinase activity and left the major part of the endogenous substrates in the insoluble fraction."}
{"id": "PMID:186030", "title": "Myosin light-chain phosphatase.", "content": "1. A method for the isolation of a new enzyme, myosin light-chain phosphatase, from rabbit white skeletal muscle by using a Sepharose-phosphorylated myosin light-chain affinity column is described. 2. The enzyme migrated as a single component on electrophoresis in sodium dodecyl sulphate/polyacrylamide gel at pH7.0, with apparent mol.wt. 70000. 3. The enzyme was highly specific for the phosphorylated P-light chain of myosin, had pH optima at 6.5 and 8.0 and was not inhibited by NaF. 4. A Ca2+-sensitive 'ATPase' (adenosine triphosphatase) system consisting of myosin light-chain kinase, myosin light-chain phosphatase and the P-light chain is described. 5. Evidence is presented for a phosphoryl exchange between Pi, phosphorylated P-light chain and myosin light-chain phosphatase. 6. Heavy meromyosin prepared by chymotryptic digestion can be phosphorylated by myosin light-chain kinase. 7. The ATPase activities of myosin and heavy meromyosin, in the presence and absence of F-actin, were not significantly changed (+/- 10%) by phosphorylation of the P-light chain.", "contents": "Myosin light-chain phosphatase. 1. A method for the isolation of a new enzyme, myosin light-chain phosphatase, from rabbit white skeletal muscle by using a Sepharose-phosphorylated myosin light-chain affinity column is described. 2. The enzyme migrated as a single component on electrophoresis in sodium dodecyl sulphate/polyacrylamide gel at pH7.0, with apparent mol.wt. 70000. 3. The enzyme was highly specific for the phosphorylated P-light chain of myosin, had pH optima at 6.5 and 8.0 and was not inhibited by NaF. 4. A Ca2+-sensitive 'ATPase' (adenosine triphosphatase) system consisting of myosin light-chain kinase, myosin light-chain phosphatase and the P-light chain is described. 5. Evidence is presented for a phosphoryl exchange between Pi, phosphorylated P-light chain and myosin light-chain phosphatase. 6. Heavy meromyosin prepared by chymotryptic digestion can be phosphorylated by myosin light-chain kinase. 7. The ATPase activities of myosin and heavy meromyosin, in the presence and absence of F-actin, were not significantly changed (+/- 10%) by phosphorylation of the P-light chain."}
{"id": "PMID:186031", "title": "Iso-cytochrome c species from baker's yeast. Analysis of their circular-dichroism spectra.", "content": "The circular-dichroism spectra of baker's-yeast iso-1- (methylated and unmethylated forms) and iso-2-cytochrome c species were examined between 200 and 600nm. In the visible region the yeast haemoproteins have characteristics nearly indistinguishable from those of horse heart cytochrome c. From the spectra in the u.v. region the latter appears, however, to be more helical. It is proposed that the likely element of non-helical structure in iso-1-cytochrome c is residues 62-70.", "contents": "Iso-cytochrome c species from baker's yeast. Analysis of their circular-dichroism spectra. The circular-dichroism spectra of baker's-yeast iso-1- (methylated and unmethylated forms) and iso-2-cytochrome c species were examined between 200 and 600nm. In the visible region the yeast haemoproteins have characteristics nearly indistinguishable from those of horse heart cytochrome c. From the spectra in the u.v. region the latter appears, however, to be more helical. It is proposed that the likely element of non-helical structure in iso-1-cytochrome c is residues 62-70."}
{"id": "PMID:186032", "title": "Ovarian adenosine 3':5'-cyclic monophosphate-dependent protein kinase(s). Regulation by choriogonadotropin and lutropin in rat ovarian cells.", "content": "Choriogonadotropin and lutropin have been found to activate cyclic AMP-dependent protein kinase in ovarian cells isolated by collagenase dispersion from immature rats. The stimulatory effect of gonadotropins was dependent on both hormone concentration and incubation time. Choriogonadotropin at 1 mug/ml fully stimulated the protein kinase activity within 5 min of incubation, and this effect was specific for choriogonadotropin and lutropin-like activity. In addition, protein kinase activity has been characterized with respect to salt sensitivity, cyclic AMP binding, and its responsiveness to gonadotropins and other peptide hormones. Ovarian protein kinase was susceptible to high salt concentrations. The addition of 0.3-1.0 M-NaCl in incubation medium increased the activity ratio with a concomitant decrease in cycle AMP-dependence. The salt effect on protein kinase was observed both from hormone-treated and untreated cells. The hormone-stimulated and unstimulated protein kinase activity was completely stable in the absence of NaCl. No change in the activity ratio was observed when cellular extracts were assayed for protein kinase activity either immediately or after 2 h in the absence of added salt. Gel filtration in the absence of NaCl of cellular extracts prepared from choriogonadotropin-treated and untreated cells showned only a single peak of protein kinase activity that was sensitive to exogenously added cyclic AMP. By contrast, when 0.5 M-NaCl was included in the column buffer, the chromatography of untreated extract showed two peaks of protein kinase activity. The first peak was sensitive to added cyclic AMP, whereas the second peak was insensitive to it. Under identical experimental conditions, protein kinase from gonadotropin-treated cells showed, on gel filtration, only one peak of activity that was totally insensitive to added cyclic AMP. DEAE-cellulose column chromatography of a 20000 g supernatant fraction resulted in a peak of kinase activity that eluted in approx. 0.15 M-NaCl, similar to the similar to the elution of type II protein kinases as described by Corbin et al. (1975) (J. Biol. Chem. 250, 218-225). Choriogonadotropin stimulation produced a decrease in the capacity of protein kinase to bind exogenous cyclic [3H]AMP, with a concomitant increase in the kinase activity ratio. These results are consistent with the notion that cyclic AMP, GENERATED IN SITU Under hormonal stimulation, binds tot he regulatory subunit of protein kinase with subsequent dissociation of the active catalytic subunit from the holoenzyme.", "contents": "Ovarian adenosine 3':5'-cyclic monophosphate-dependent protein kinase(s). Regulation by choriogonadotropin and lutropin in rat ovarian cells. Choriogonadotropin and lutropin have been found to activate cyclic AMP-dependent protein kinase in ovarian cells isolated by collagenase dispersion from immature rats. The stimulatory effect of gonadotropins was dependent on both hormone concentration and incubation time. Choriogonadotropin at 1 mug/ml fully stimulated the protein kinase activity within 5 min of incubation, and this effect was specific for choriogonadotropin and lutropin-like activity. In addition, protein kinase activity has been characterized with respect to salt sensitivity, cyclic AMP binding, and its responsiveness to gonadotropins and other peptide hormones. Ovarian protein kinase was susceptible to high salt concentrations. The addition of 0.3-1.0 M-NaCl in incubation medium increased the activity ratio with a concomitant decrease in cycle AMP-dependence. The salt effect on protein kinase was observed both from hormone-treated and untreated cells. The hormone-stimulated and unstimulated protein kinase activity was completely stable in the absence of NaCl. No change in the activity ratio was observed when cellular extracts were assayed for protein kinase activity either immediately or after 2 h in the absence of added salt. Gel filtration in the absence of NaCl of cellular extracts prepared from choriogonadotropin-treated and untreated cells showned only a single peak of protein kinase activity that was sensitive to exogenously added cyclic AMP. By contrast, when 0.5 M-NaCl was included in the column buffer, the chromatography of untreated extract showed two peaks of protein kinase activity. The first peak was sensitive to added cyclic AMP, whereas the second peak was insensitive to it. Under identical experimental conditions, protein kinase from gonadotropin-treated cells showed, on gel filtration, only one peak of activity that was totally insensitive to added cyclic AMP. DEAE-cellulose column chromatography of a 20000 g supernatant fraction resulted in a peak of kinase activity that eluted in approx. 0.15 M-NaCl, similar to the similar to the elution of type II protein kinases as described by Corbin et al. (1975) (J. Biol. Chem. 250, 218-225). Choriogonadotropin stimulation produced a decrease in the capacity of protein kinase to bind exogenous cyclic [3H]AMP, with a concomitant increase in the kinase activity ratio. These results are consistent with the notion that cyclic AMP, GENERATED IN SITU Under hormonal stimulation, binds tot he regulatory subunit of protein kinase with subsequent dissociation of the active catalytic subunit from the holoenzyme."}
{"id": "PMID:186033", "title": "The effect of intracellular calcium ions on adrenaline-stimulated adenosine 3':5'-cyclic monophosphate concentrations in pigeon erythrocytes, studied by using the ionophore A23187.", "content": "1. The bivalent cation ionophore A23187 was used to increase the intracellular concentration of Ca2+ in pigeon erythrocytes to investigate whether the increase in cyclic AMP content caused by adrenaline might be influenced by a change in intracellular Ca2+ in intact cells. 2. Incubation of cells with adrenaline, in the concentration range 0.55--55 muM, resulted in an increase in the concentration of cyclic AMP over a period of 60 min. The effect of adrenaline was inhibited by more than 90% with ionophore A23187 (1.9 muM) in the presence of 1 mM-Ca2+. This inhibition could be decreased by decreasing either the concentration of the ionophore or the concentration of extracellular Ca2+, and was independent of the concentration of adrenaline. 3. The effect of ionophore A23187 depended on the time of incubation. Time-course studies showed that maximum inhibition by ionophore A23187 was only observed when the cells were incubated with the ionophore for at least 15 min before the addition of adrenaline. 4. The inhibition by ionophore A23187 depended on the concentration of extracellular Ca2+. In the absence of Mg2+, ionophore A23187 (1.9 muM) inhibited the effect of adrenaline by approx. 30% without added Ca2+, by approx. 66% with 10 muM-Ca2+ and by more than 90% with concentrations of added Ca2+ greater than 30 muM. However, even in the presence of EGTA [ethanedioxybis(ethylamine)tetra-acetate](0.1--10 mM), ionophore A23187 caused an inhibition of the cyclic AMP response of at least 30%, which may have been due to a decrease in cell Mg2+ concentration. 5. The addition of EGTA after incubation of cells with ionophore A23187 resulted in a partial reversal of the inhibition of the effect of adrenaline. 6. Inclusion of Mg2+ (2 mM) in the incubation medium antagonized the inhibitory action of ionophore A23187. This effect was most marked when the ionophore A23187 was added to medium containing Mg2+ before the addition of the cells. 7. The cellular content of Mg2+ was decreased by approx. 50% after 20 min incubation with ionophore A23187 (1.9 muM) in the presence of Ca2+ (1 mM) but no Mg2+. When Mg2+ (2 mM) was also present in the medium, ionophore A23187 caused an increase of approx. 80% in cell Mg2+ content. Ionophore A23187 had no significant effect on cell K+ content. 8. Ionophore A23187 caused a decrease in cell ATP content under some conditions. Since effects on cyclic AMP content could also be shown when ATP was not significanlty lowered, it appeared that a decrease in ATP in the cells could not explain the effect of ionophore A23187 on cyclic AMP. 9. Ionophore A23187 (1.9 muM), with 1 mM-Ca2+, did not enhance cyclic AMP degradation in intact cells, suggesting that the effect of ionophore A23187 on cyclic AMP content was mediated through an inhibition of adenylate cyclase rather than a stimulation of cyclic AMP phosphodiesterase. 10. It was concluded that in intact pigeon erythrocytes adenylate cyclase may be inhibited by intracellular concentrations of Ca2+ in the range 1-10 muM.", "contents": "The effect of intracellular calcium ions on adrenaline-stimulated adenosine 3':5'-cyclic monophosphate concentrations in pigeon erythrocytes, studied by using the ionophore A23187. 1. The bivalent cation ionophore A23187 was used to increase the intracellular concentration of Ca2+ in pigeon erythrocytes to investigate whether the increase in cyclic AMP content caused by adrenaline might be influenced by a change in intracellular Ca2+ in intact cells. 2. Incubation of cells with adrenaline, in the concentration range 0.55--55 muM, resulted in an increase in the concentration of cyclic AMP over a period of 60 min. The effect of adrenaline was inhibited by more than 90% with ionophore A23187 (1.9 muM) in the presence of 1 mM-Ca2+. This inhibition could be decreased by decreasing either the concentration of the ionophore or the concentration of extracellular Ca2+, and was independent of the concentration of adrenaline. 3. The effect of ionophore A23187 depended on the time of incubation. Time-course studies showed that maximum inhibition by ionophore A23187 was only observed when the cells were incubated with the ionophore for at least 15 min before the addition of adrenaline. 4. The inhibition by ionophore A23187 depended on the concentration of extracellular Ca2+. In the absence of Mg2+, ionophore A23187 (1.9 muM) inhibited the effect of adrenaline by approx. 30% without added Ca2+, by approx. 66% with 10 muM-Ca2+ and by more than 90% with concentrations of added Ca2+ greater than 30 muM. However, even in the presence of EGTA [ethanedioxybis(ethylamine)tetra-acetate](0.1--10 mM), ionophore A23187 caused an inhibition of the cyclic AMP response of at least 30%, which may have been due to a decrease in cell Mg2+ concentration. 5. The addition of EGTA after incubation of cells with ionophore A23187 resulted in a partial reversal of the inhibition of the effect of adrenaline. 6. Inclusion of Mg2+ (2 mM) in the incubation medium antagonized the inhibitory action of ionophore A23187. This effect was most marked when the ionophore A23187 was added to medium containing Mg2+ before the addition of the cells. 7. The cellular content of Mg2+ was decreased by approx. 50% after 20 min incubation with ionophore A23187 (1.9 muM) in the presence of Ca2+ (1 mM) but no Mg2+. When Mg2+ (2 mM) was also present in the medium, ionophore A23187 caused an increase of approx. 80% in cell Mg2+ content. Ionophore A23187 had no significant effect on cell K+ content. 8. Ionophore A23187 caused a decrease in cell ATP content under some conditions. Since effects on cyclic AMP content could also be shown when ATP was not significanlty lowered, it appeared that a decrease in ATP in the cells could not explain the effect of ionophore A23187 on cyclic AMP. 9. Ionophore A23187 (1.9 muM), with 1 mM-Ca2+, did not enhance cyclic AMP degradation in intact cells, suggesting that the effect of ionophore A23187 on cyclic AMP content was mediated through an inhibition of adenylate cyclase rather than a stimulation of cyclic AMP phosphodiesterase. 10. It was concluded that in intact pigeon erythrocytes adenylate cyclase may be inhibited by intracellular concentrations of Ca2+ in the range 1-10 muM."}
{"id": "PMID:186034", "title": "Triacylglycerol biosynthesis in the adipose tissue of the obese-hyperglycaemic mouse.", "content": "Obesity in obese-hyperglycaemic mouse is associated with an increase in number and size of adipocytes. Adipocytes from the obese mouse showed increased incorporation of [14C]acetate and[14C]glucose into triacylglycerol. This increased capacity of triacylglycerol formation was correlated with increased activities of various triacylglycerol-forming enzymes measured in the microsomal fraction of adipose tissue from obese mice. Microsomal fractions from lean and obese mice contained sn-glycerol 3-phosphate acyltransferase, phosphatidate phosphohydrolase and diacylglycerol acyltransferase. Phosphatidate phosphohydrolase was also detected in the soluble fraction. In the presence of Mg2+, the phosphatidate phsophohydrolase from the soluble and the microsomal fractions was active towards membrane-bound phosphatidate. Among the three enzymes studied here, the increase in Mg2+-dependent phosphatidate phosphohydrolase was most prominent in adipose tissue of obese mice.", "contents": "Triacylglycerol biosynthesis in the adipose tissue of the obese-hyperglycaemic mouse. Obesity in obese-hyperglycaemic mouse is associated with an increase in number and size of adipocytes. Adipocytes from the obese mouse showed increased incorporation of [14C]acetate and[14C]glucose into triacylglycerol. This increased capacity of triacylglycerol formation was correlated with increased activities of various triacylglycerol-forming enzymes measured in the microsomal fraction of adipose tissue from obese mice. Microsomal fractions from lean and obese mice contained sn-glycerol 3-phosphate acyltransferase, phosphatidate phosphohydrolase and diacylglycerol acyltransferase. Phosphatidate phosphohydrolase was also detected in the soluble fraction. In the presence of Mg2+, the phosphatidate phsophohydrolase from the soluble and the microsomal fractions was active towards membrane-bound phosphatidate. Among the three enzymes studied here, the increase in Mg2+-dependent phosphatidate phosphohydrolase was most prominent in adipose tissue of obese mice."}
{"id": "PMID:186035", "title": "Inosine-stimulated insulin release and metabolism of inosine in isolated mouse pancreatic islets.", "content": "Inosine is a potent primary stimulus of insulin secretion from isolated mouse islets. The inosine-induced insulin secretion was totally depressed during starvation, but was completely restored by the addition of 5 mM-caffeine to the medium and partially restored by the addition of 5 mM-glucose. Mannoheptulose (3 mg/ml) potentiated the effect of 10 mM-inosine in islets from fed mice. The mechanism of the stimulatory effect of inosine was further investigated, and it was demonstrated that pancreatic islets contain a nucleoside phosphorylase capable of converting inosine into hypoxanthine and ribose 1-phosphate. Inosine at 10 mM concentration increased the lactate production and the content of ATP, glucose 6-phosphate (fructose 1,6-diphosphate + triose phosphates) and cyclic AMP in islets from fed mice. In islets from starved mice inosine-induced lactate production was decreased and no change in the concentration of cyclic AMP could be demonstrated, whereas the concentration of ATP and glucose 6-phosphate rose. Inosine (10 mM) induced a higher concentration of (fructose 1,6-diphosphate + triose phosphates) in islets from starved mice than in islets from fed mice suggesting that in starvation the activities of glyceraldehyde 3-phosphate dehydrogenase or other enzymes below this step in glycolysis are decreased. Formation of glucose from inosine was negligible. Inosine had no direct effect on adenylate cyclase activity in islet homogenates. The observed changes in insulin secretion and islet metabolism mimic what is seen when glucose and glyceraldehyde stimulate insulin secretion, and as neither ribose nor hypoxanthine-stimulated insulin release, the results are interpreted as supporting the substrate-site hypothesis for glucose-induced insulin secretion according to which glucose has to be metabolized in the beta-cells before secretion is initiated.", "contents": "Inosine-stimulated insulin release and metabolism of inosine in isolated mouse pancreatic islets. Inosine is a potent primary stimulus of insulin secretion from isolated mouse islets. The inosine-induced insulin secretion was totally depressed during starvation, but was completely restored by the addition of 5 mM-caffeine to the medium and partially restored by the addition of 5 mM-glucose. Mannoheptulose (3 mg/ml) potentiated the effect of 10 mM-inosine in islets from fed mice. The mechanism of the stimulatory effect of inosine was further investigated, and it was demonstrated that pancreatic islets contain a nucleoside phosphorylase capable of converting inosine into hypoxanthine and ribose 1-phosphate. Inosine at 10 mM concentration increased the lactate production and the content of ATP, glucose 6-phosphate (fructose 1,6-diphosphate + triose phosphates) and cyclic AMP in islets from fed mice. In islets from starved mice inosine-induced lactate production was decreased and no change in the concentration of cyclic AMP could be demonstrated, whereas the concentration of ATP and glucose 6-phosphate rose. Inosine (10 mM) induced a higher concentration of (fructose 1,6-diphosphate + triose phosphates) in islets from starved mice than in islets from fed mice suggesting that in starvation the activities of glyceraldehyde 3-phosphate dehydrogenase or other enzymes below this step in glycolysis are decreased. Formation of glucose from inosine was negligible. Inosine had no direct effect on adenylate cyclase activity in islet homogenates. The observed changes in insulin secretion and islet metabolism mimic what is seen when glucose and glyceraldehyde stimulate insulin secretion, and as neither ribose nor hypoxanthine-stimulated insulin release, the results are interpreted as supporting the substrate-site hypothesis for glucose-induced insulin secretion according to which glucose has to be metabolized in the beta-cells before secretion is initiated."}
{"id": "PMID:186036", "title": "Intracellular enzymes of collagen biosynthesis in rat liver as a function of age and in hepatic injury induced by dimethylnitrosamine. Changes in prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase and collagen glucosyltransferase activities.", "content": "The relationship between the changes in the four enzyme activities catalysing intracellular post-translational modifications in collagen biosynthesis were studied in rat liver as a function of age and in experimental hepatic injury induced by the administration of dimethylnitrosamine. During aging, relatively large changes were found in prolyl hydroxylase and lysyl hydroxylase activities, whereas only minor changes took place in collagen galactosyltransferase and collagen glucosyltransferase activities. In hepatic injury, the two hydroxylase activities increased earlier and to a larger extent than did the two glycosyltransferase activities, and the largest was found in lysyl hydroxylase activity. The data support previous suggestions that changes in the rate of collagen biosynthesis in the liver cannot be explained simply by a change in the number of collagen-producing cells, but regulation of the enzyme activities existed, so that the two hydroxylase activities altered considerably more than did the two collagen glycosyltransferase activities.", "contents": "Intracellular enzymes of collagen biosynthesis in rat liver as a function of age and in hepatic injury induced by dimethylnitrosamine. Changes in prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase and collagen glucosyltransferase activities. The relationship between the changes in the four enzyme activities catalysing intracellular post-translational modifications in collagen biosynthesis were studied in rat liver as a function of age and in experimental hepatic injury induced by the administration of dimethylnitrosamine. During aging, relatively large changes were found in prolyl hydroxylase and lysyl hydroxylase activities, whereas only minor changes took place in collagen galactosyltransferase and collagen glucosyltransferase activities. In hepatic injury, the two hydroxylase activities increased earlier and to a larger extent than did the two glycosyltransferase activities, and the largest was found in lysyl hydroxylase activity. The data support previous suggestions that changes in the rate of collagen biosynthesis in the liver cannot be explained simply by a change in the number of collagen-producing cells, but regulation of the enzyme activities existed, so that the two hydroxylase activities altered considerably more than did the two collagen glycosyltransferase activities."}
{"id": "PMID:186037", "title": "Intracellular enzymes of collagen biosynthesis in rat liver as a function of age and in hepatic injury induced by dimethylnitrosamine. Purification of rat prolyl hydroxylase and comparison of changes in prolyl hydroxylase activity with changes in immunoreactive prolyl hydroxylase.", "content": "Prolyl hydroxylase was purified from newborn rats by affinity chromatography using poly(L-proline), and antiserum to the enzyme was prepared in rabbits. The rat prolyl hydroxylase was similar to the chick and human enzymes with respect to specific activity, molecular weight and molecular weights of the polypeptide chains. The activity of prolyl hydroxylase and the content of immunoreactive enzyme were measured in rat liver as a function of age in experimental hepatic injury. Active prolyl hydroxylase comprised about 13.2% of the total immunoreactive protein in the liver of newborn rats and the value decreased to about 3.6% at the age of 420 days. This decrease was due to a decrease in the enzyme activity, whereas only minor changes were found in the content of the immunoreactive protein. In hepatic injury, a significant increase was found in the ratio of active enzyme to total immunoreactive protein, owing to an increase in the enzyme activity. The data indicate that prolyl hydroxylase activity in rat liver is controlled in part by a mechanism which does not involve changes in the content of the total immunoreactive protein.", "contents": "Intracellular enzymes of collagen biosynthesis in rat liver as a function of age and in hepatic injury induced by dimethylnitrosamine. Purification of rat prolyl hydroxylase and comparison of changes in prolyl hydroxylase activity with changes in immunoreactive prolyl hydroxylase. Prolyl hydroxylase was purified from newborn rats by affinity chromatography using poly(L-proline), and antiserum to the enzyme was prepared in rabbits. The rat prolyl hydroxylase was similar to the chick and human enzymes with respect to specific activity, molecular weight and molecular weights of the polypeptide chains. The activity of prolyl hydroxylase and the content of immunoreactive enzyme were measured in rat liver as a function of age in experimental hepatic injury. Active prolyl hydroxylase comprised about 13.2% of the total immunoreactive protein in the liver of newborn rats and the value decreased to about 3.6% at the age of 420 days. This decrease was due to a decrease in the enzyme activity, whereas only minor changes were found in the content of the immunoreactive protein. In hepatic injury, a significant increase was found in the ratio of active enzyme to total immunoreactive protein, owing to an increase in the enzyme activity. The data indicate that prolyl hydroxylase activity in rat liver is controlled in part by a mechanism which does not involve changes in the content of the total immunoreactive protein."}
{"id": "PMID:186038", "title": "Precocious development of UDP-glucuronyltransferase activity in chick-embryo liver after administration of adrenocorticotropic hormone and of certain 11beta-hydroxy corticosteroids.", "content": "1. Precocious development of UDP-glucuronyltransferase (EC 2.4.1.17) and of glucuronidation by endogenous compounds of known chemical composition is reported for the first time. 2. This development occurs precociously in chick-embryo liver after administration to the egg of mammalian adrenocorticotropic hormone, of Synacthen (a synthetic compound possessing adrenocorticotropic activity), or of certain corticosteroids possessing a hydroxy or an oxo group at C-11. 3. Corticosterone-dependent transferase development parallels the rise of infused corticosterone in plasma, but does not require the presence of embryo pituitary in ovo, and is demonstrable in embryo liver explants in vitro. 4. Competence of embryo liver transferase to respond to corticosterone (or dexamethasone) begins over days 13-14, the time of competence to respond to grafted pituitary gland. 5. The transferase appearing after treatment with corticosterone or adrenocorticotropic hormone, like that appearing after pituitary grafting or on natural development and unlike that from the untreated embryo, is markedly activated by membrane-perturbation procedures, suggesting it appears through induction, not activation. 6. Thyroxine and tri-iodothyronine accelerate transferase development after treatment with adrenocorticotropic hormone or corticosteroid to the rate seen after pituitary grafting. 7. A wide range of other hormones and steroids did not obviously influence transferase development in this system. 8. We suggest that grafted pituitary gland evokes precocious transferase development in embryo liver through production of adrenocorticotropic hormone and hence of the active corticosteroids; thyrotropin and thyroxine hasten the process. The role of this mechanism in the natural development of UDP-glucuronyltransferase is discussed.", "contents": "Precocious development of UDP-glucuronyltransferase activity in chick-embryo liver after administration of adrenocorticotropic hormone and of certain 11beta-hydroxy corticosteroids. 1. Precocious development of UDP-glucuronyltransferase (EC 2.4.1.17) and of glucuronidation by endogenous compounds of known chemical composition is reported for the first time. 2. This development occurs precociously in chick-embryo liver after administration to the egg of mammalian adrenocorticotropic hormone, of Synacthen (a synthetic compound possessing adrenocorticotropic activity), or of certain corticosteroids possessing a hydroxy or an oxo group at C-11. 3. Corticosterone-dependent transferase development parallels the rise of infused corticosterone in plasma, but does not require the presence of embryo pituitary in ovo, and is demonstrable in embryo liver explants in vitro. 4. Competence of embryo liver transferase to respond to corticosterone (or dexamethasone) begins over days 13-14, the time of competence to respond to grafted pituitary gland. 5. The transferase appearing after treatment with corticosterone or adrenocorticotropic hormone, like that appearing after pituitary grafting or on natural development and unlike that from the untreated embryo, is markedly activated by membrane-perturbation procedures, suggesting it appears through induction, not activation. 6. Thyroxine and tri-iodothyronine accelerate transferase development after treatment with adrenocorticotropic hormone or corticosteroid to the rate seen after pituitary grafting. 7. A wide range of other hormones and steroids did not obviously influence transferase development in this system. 8. We suggest that grafted pituitary gland evokes precocious transferase development in embryo liver through production of adrenocorticotropic hormone and hence of the active corticosteroids; thyrotropin and thyroxine hasten the process. The role of this mechanism in the natural development of UDP-glucuronyltransferase is discussed."}
{"id": "PMID:186039", "title": "Transport of sugars in chick-embryo fibroblasts. Evidence for a low-affinity system and a high-affinity system for glucose transport.", "content": "The rate of D-glucose uptake by cells that had been deprived of sugar for 18-24h was consistently observed to be 15-20 times higher than that in control cells maintained for the same length of time in medium containing glucose. This increased rate of glucose transport by sugar-starved cells was due to a 3-5-fold increase in the Vmax. value of a low-affinity system (Km 1 mM) combined with an increase in the Vmax of a separate high-affinity system (Km 0.05-0.2 mM). The high-affinity system, which was most characteristic of starved cells, was particularly sensitive to low concentrations of the thiol reagent N-ethylmaleimide; 50% inhibition of uptake occurred at approx. 0.01 mM-N-ethylmaleimide. In contrast with the high-affinity system, the low-affinity system of either the fed cells or the starved cells was unaffected by N-ethylmaleimide. In addition to the increases in the rate of D-glucose transport, cells deprived of sugar had increased rates of transport of 3-O-methyl-D-glucose and 2-deoxy-D-glucose. No measurable high-affinity transport system could be demonstrated for the transport of 3-O-methylgucose, and N-ethylmaleimide did not alter the initial rate. Thus the transport of 3-O-methyglucose by both fed and starved cells was exclusively by the N-ethylmaleimide-insensitive low-affinity system. The low-affinity system also appeared to be the primary means for the transport of 2-deoxyglucose by fed and starved cells. However, some of the transport of 2-deoxyglucose by starved cells was inhibited by N-ethylmaleimide, suggesting that 2-deoxyglucose may also be transported by a high-affinity system. The results of experiments that measured transport kinetics strongly suggest that glucose can be transported by a least two separate systems, and 3-O-methylglucose and 2-deoxyglucose by one. Support for these interpretations comes from the analysis of the effects of N-ethylmaleimide and cycloheximide as well as from the results of competition experiments. The uptake of glucose is quite different from that of 2-deoxyglucose and 3-O-methylglucose. The net result of sugar starvation serves to emphasize these differences. The apparent de-repression of the transport systems studied presents an interesting basis for further studies of the regulation of transport in a variety of cells.", "contents": "Transport of sugars in chick-embryo fibroblasts. Evidence for a low-affinity system and a high-affinity system for glucose transport. The rate of D-glucose uptake by cells that had been deprived of sugar for 18-24h was consistently observed to be 15-20 times higher than that in control cells maintained for the same length of time in medium containing glucose. This increased rate of glucose transport by sugar-starved cells was due to a 3-5-fold increase in the Vmax. value of a low-affinity system (Km 1 mM) combined with an increase in the Vmax of a separate high-affinity system (Km 0.05-0.2 mM). The high-affinity system, which was most characteristic of starved cells, was particularly sensitive to low concentrations of the thiol reagent N-ethylmaleimide; 50% inhibition of uptake occurred at approx. 0.01 mM-N-ethylmaleimide. In contrast with the high-affinity system, the low-affinity system of either the fed cells or the starved cells was unaffected by N-ethylmaleimide. In addition to the increases in the rate of D-glucose transport, cells deprived of sugar had increased rates of transport of 3-O-methyl-D-glucose and 2-deoxy-D-glucose. No measurable high-affinity transport system could be demonstrated for the transport of 3-O-methylgucose, and N-ethylmaleimide did not alter the initial rate. Thus the transport of 3-O-methyglucose by both fed and starved cells was exclusively by the N-ethylmaleimide-insensitive low-affinity system. The low-affinity system also appeared to be the primary means for the transport of 2-deoxyglucose by fed and starved cells. However, some of the transport of 2-deoxyglucose by starved cells was inhibited by N-ethylmaleimide, suggesting that 2-deoxyglucose may also be transported by a high-affinity system. The results of experiments that measured transport kinetics strongly suggest that glucose can be transported by a least two separate systems, and 3-O-methylglucose and 2-deoxyglucose by one. Support for these interpretations comes from the analysis of the effects of N-ethylmaleimide and cycloheximide as well as from the results of competition experiments. The uptake of glucose is quite different from that of 2-deoxyglucose and 3-O-methylglucose. The net result of sugar starvation serves to emphasize these differences. The apparent de-repression of the transport systems studied presents an interesting basis for further studies of the regulation of transport in a variety of cells."}
{"id": "PMID:186040", "title": "Plasma-membrane components can be removed from isolated lymphocytes by the bile salts glycocholate and taurocholate without cell lysis.", "content": "Glycocholate and taurocholate removed from isolated pig lymphocytes a proportion of the cells' complement of 5'-nucleotidase, alkaline phosphatase and alkaline phosphodiesterase I before cell lysis. This may indicate a loss of externally orientated plasma-membrane components.", "contents": "Plasma-membrane components can be removed from isolated lymphocytes by the bile salts glycocholate and taurocholate without cell lysis. Glycocholate and taurocholate removed from isolated pig lymphocytes a proportion of the cells' complement of 5'-nucleotidase, alkaline phosphatase and alkaline phosphodiesterase I before cell lysis. This may indicate a loss of externally orientated plasma-membrane components."}
{"id": "PMID:186041", "title": "Testosterone and 6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate stimulate protein and lysosomal enzyme secretion in rat seminal vesicle.", "content": "Rat seminal-vesicle secretion was studied in vitro in a slice-incubation system. Seminal-vesicle slices were preincubated with 32Pi for 15 min, rinsed, and incubated in an isotope-free 'chase' medium for up to 4h. Gland slices spontaneously discharged protein, three lysosomal hydrolases and trichloroacetic acid-insoluble 32P into the medium in a time- and temperature-dependent manner. Testosterone (10 muM) and dibutyryl cyclic AMP (1 mM) stimulated the discharge of protein, acid hydrolases and trichloroacetic acid-insoluble 32P, and also stimulated the incorporation of 32Pi into trichloroacetic acid-insoluble components. The acid phosphatase and beta-N-acetylhexosaminidase isoenzymes were separated by isoelectric focusing. These hydrolases were secreted into the medium as acidic isoenzymes, presumably contained within primary lysosomes, whereas they occurred largely as less acidic and basic isoenzymes in the glandular tissue.", "contents": "Testosterone and 6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate stimulate protein and lysosomal enzyme secretion in rat seminal vesicle. Rat seminal-vesicle secretion was studied in vitro in a slice-incubation system. Seminal-vesicle slices were preincubated with 32Pi for 15 min, rinsed, and incubated in an isotope-free 'chase' medium for up to 4h. Gland slices spontaneously discharged protein, three lysosomal hydrolases and trichloroacetic acid-insoluble 32P into the medium in a time- and temperature-dependent manner. Testosterone (10 muM) and dibutyryl cyclic AMP (1 mM) stimulated the discharge of protein, acid hydrolases and trichloroacetic acid-insoluble 32P, and also stimulated the incorporation of 32Pi into trichloroacetic acid-insoluble components. The acid phosphatase and beta-N-acetylhexosaminidase isoenzymes were separated by isoelectric focusing. These hydrolases were secreted into the medium as acidic isoenzymes, presumably contained within primary lysosomes, whereas they occurred largely as less acidic and basic isoenzymes in the glandular tissue."}
{"id": "PMID:186043", "title": "Lowered respiratory activity in hypo-osmotically shocked mitochondria without loss of cytochrome c.", "content": "Brief exposure of rat liver mitochondria to hypo-osmotic sucrose media caused a decline in the rates of succinate and ascorbate-NNN'N'-tetramethyl-p-phenylenediamine oxidation without loss of cytochrome c when assayed in iso-osmotic media. Lowered respiration rates in mitochondria after brief exposure to hypo-osmotic media may reflect a modification of cytochrome c binding.", "contents": "Lowered respiratory activity in hypo-osmotically shocked mitochondria without loss of cytochrome c. Brief exposure of rat liver mitochondria to hypo-osmotic sucrose media caused a decline in the rates of succinate and ascorbate-NNN'N'-tetramethyl-p-phenylenediamine oxidation without loss of cytochrome c when assayed in iso-osmotic media. Lowered respiration rates in mitochondria after brief exposure to hypo-osmotic media may reflect a modification of cytochrome c binding."}
{"id": "PMID:186042", "title": "Activities and some properties of adenylate cyclase and phosphodiesterase in muscle, liver and nervous tissues from vertebrates and invertebrates in relation to the control of the concentration of adenosine 3':5'-cyclic monophosphate.", "content": "1. The basal and fluoride-stimulated activities of adenylate cyclase, and the maximal activities of 3':5'-cyclic AMP phosphodiesterase and 3':5'-cyclic GMP phosphodiesterase, together with the Km values for their respective substrates, were measured in muscle, liver and nervous tissues from a large range of animals to provide information on the mechanism of control of cyclic AMP concentrations in these tissues. High activities of adenylate cyclase and cyclic AMP diesterase are found in nervous tissues and in the more aerobic muscles (e.g. insect flight muscles, cardiac muscle and some vertebrate skeletal muscles). The activities of these enzymes in liver are similar to those in the heart of the same animal. The Km values for the enzymes from different tissues and animals are remarkably similar. 2. The comparison of cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase activities suggests that in vertebrate tissues only one enzyme (the high-Km enzyme), which possesses dual specificity, exists, whereas in invertebrate tissues there are at least two phosphodiesterases with separate specificities. 3. A simple quantitative model to explain the control of the steady-state concentrations of cyclic AMP is proposed. The maximum increase in cyclic AMP concentration predicted by comparison of basal with fluoride-stimulated activities of adenylate cyclase is compared with the maximum increases in concentration produced in the intact tissue by hormonal stimulation: reasonable agreement is obtained. The model is also used to predict the actual concentrations and the rates of turnover of cyclic AMP in different tissues and, where possible, these values are compared with reported values. Reasonable agreement is found between predicted and reported values. The possible physiological significances of different rates of turnover of cyclic AMP and the different ratios of high- and low-Km phosphodiesterases in different tissues are discussed.", "contents": "Activities and some properties of adenylate cyclase and phosphodiesterase in muscle, liver and nervous tissues from vertebrates and invertebrates in relation to the control of the concentration of adenosine 3':5'-cyclic monophosphate. 1. The basal and fluoride-stimulated activities of adenylate cyclase, and the maximal activities of 3':5'-cyclic AMP phosphodiesterase and 3':5'-cyclic GMP phosphodiesterase, together with the Km values for their respective substrates, were measured in muscle, liver and nervous tissues from a large range of animals to provide information on the mechanism of control of cyclic AMP concentrations in these tissues. High activities of adenylate cyclase and cyclic AMP diesterase are found in nervous tissues and in the more aerobic muscles (e.g. insect flight muscles, cardiac muscle and some vertebrate skeletal muscles). The activities of these enzymes in liver are similar to those in the heart of the same animal. The Km values for the enzymes from different tissues and animals are remarkably similar. 2. The comparison of cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase activities suggests that in vertebrate tissues only one enzyme (the high-Km enzyme), which possesses dual specificity, exists, whereas in invertebrate tissues there are at least two phosphodiesterases with separate specificities. 3. A simple quantitative model to explain the control of the steady-state concentrations of cyclic AMP is proposed. The maximum increase in cyclic AMP concentration predicted by comparison of basal with fluoride-stimulated activities of adenylate cyclase is compared with the maximum increases in concentration produced in the intact tissue by hormonal stimulation: reasonable agreement is obtained. The model is also used to predict the actual concentrations and the rates of turnover of cyclic AMP in different tissues and, where possible, these values are compared with reported values. Reasonable agreement is found between predicted and reported values. The possible physiological significances of different rates of turnover of cyclic AMP and the different ratios of high- and low-Km phosphodiesterases in different tissues are discussed."}
{"id": "PMID:186077", "title": "Composition of HDL-2 and HDL-3 in familial hyperalphalipoproteinemia.", "content": "The content and percent composition of cholesterol, triglyceride, phospholipids, and total proteins in HDL-2 and HDL-3 were quantitated in 5 women with familial hyperalphalipoproteinemia to determine if there are any distinctive characteristics of the high density lipoproteins in this heritable disorder. The 5 women with familial hyperalphalipoproteinemia (FHA) were compared to 4 normal women, with the groups being comparable in regards to age (40 +/- 3 and 37 +/- 5 years), total plasma cholesterol (202 +/- 9 and 188 +/- 16 mg/100 ml), triglyceride (75 +/- 12 and 95 +/- 19), and differing in levels of high density lipoprotein cholesterol (C-HDL, 84 +/- 6 and 61 +/- 3 mg/100 ml) respectively. Total cholesterol in the HDL-2 and HDL-3 fractions obtained by ultracentrifugation were 43.2 +/- 3.3 and 33.8 +/- 4.1 in FHA subjects, higher than total cholesterol in HDL-2 and HDL-3 in normals, 25.8 +/- 6.2 and 21.5 +/- 1.3 mg/100 ml, P less than 0.025. Total concentration of HDL-3 was higher in FHA than in normal subjects, respectively 222.4 +/- 22.6 and 149 +/- 7.2 mg/100 ml, P less than 0.025. Lipid-protein percent composition of HDL-2 and HDL-3 in FHA and normals was nearly identical, and polyacrylamide gel electrophoresis revealed no qualitative differences in band migration and appearance of the HDL-2 and HDL-3 fractions in normal and FHA subjects. In these women with FHA, there appears to be an increased concentration of normal HDL-2 and HDL-3.", "contents": "Composition of HDL-2 and HDL-3 in familial hyperalphalipoproteinemia. The content and percent composition of cholesterol, triglyceride, phospholipids, and total proteins in HDL-2 and HDL-3 were quantitated in 5 women with familial hyperalphalipoproteinemia to determine if there are any distinctive characteristics of the high density lipoproteins in this heritable disorder. The 5 women with familial hyperalphalipoproteinemia (FHA) were compared to 4 normal women, with the groups being comparable in regards to age (40 +/- 3 and 37 +/- 5 years), total plasma cholesterol (202 +/- 9 and 188 +/- 16 mg/100 ml), triglyceride (75 +/- 12 and 95 +/- 19), and differing in levels of high density lipoprotein cholesterol (C-HDL, 84 +/- 6 and 61 +/- 3 mg/100 ml) respectively. Total cholesterol in the HDL-2 and HDL-3 fractions obtained by ultracentrifugation were 43.2 +/- 3.3 and 33.8 +/- 4.1 in FHA subjects, higher than total cholesterol in HDL-2 and HDL-3 in normals, 25.8 +/- 6.2 and 21.5 +/- 1.3 mg/100 ml, P less than 0.025. Total concentration of HDL-3 was higher in FHA than in normal subjects, respectively 222.4 +/- 22.6 and 149 +/- 7.2 mg/100 ml, P less than 0.025. Lipid-protein percent composition of HDL-2 and HDL-3 in FHA and normals was nearly identical, and polyacrylamide gel electrophoresis revealed no qualitative differences in band migration and appearance of the HDL-2 and HDL-3 fractions in normal and FHA subjects. In these women with FHA, there appears to be an increased concentration of normal HDL-2 and HDL-3."}
{"id": "PMID:186078", "title": "Modification of nicotinic acid and prostaglandin E1 antilipolytic action in vitro.", "content": "In epididymal adipose tissue from rats, human serum antagonizes inhibition of basal lipolysis by nicotinic acid in vitro. Under similar conditions caffeine-stimulated lipolysis was unaffected by the presence of human serum. Very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins were all found to antagonize the action of nicotinic acid on basal lipolysis. VLDL also antagonized prostaglandin E1 (PGE1)-inhibition of basal lipolysis in vitro. The fat cell membrane was suggested as the site at which human serum lipoproteins antagonize nicotinic acid or PGE1 antilipolytic action on basal lipolysis in vitro.", "contents": "Modification of nicotinic acid and prostaglandin E1 antilipolytic action in vitro. In epididymal adipose tissue from rats, human serum antagonizes inhibition of basal lipolysis by nicotinic acid in vitro. Under similar conditions caffeine-stimulated lipolysis was unaffected by the presence of human serum. Very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins were all found to antagonize the action of nicotinic acid on basal lipolysis. VLDL also antagonized prostaglandin E1 (PGE1)-inhibition of basal lipolysis in vitro. The fat cell membrane was suggested as the site at which human serum lipoproteins antagonize nicotinic acid or PGE1 antilipolytic action on basal lipolysis in vitro."}
{"id": "PMID:186079", "title": "The release of an immobilized lipoprotein fraction from atherosclerotic lesions by incubation with plasmin.", "content": "A large amount of plasma low density lipoprotein is present in human aortic intima, and this can be removed and measured by electrophoresis directly from the minced tissue into an antibody-containing gel. We now find that, in addition to this electrophoretically mobile lipoprotein, there is an immobilized lipoprotein fraction than can be released from lesions by incubation of the tissue sample with plasmin or other proteolytic enzymes after the mobile lipoprotein has been removed. The concentration of immobilized lipoprotein is highly correlated with the concentration of the residual cholesterol (not mobile on electrophoresis) that has accumulated in the tissue (r = 0.702; P less than 0.001). Thus, in normal intima and early gelatinous lesions it is about 15% of the concentration of mobile lipoprotein, whereas in the atheroma lipid layers of fibrous or gelatinous plaques it may be 2 or 3 times greater than the concentration of mobile lipoprotein. This suggests that immobilization of plasma lipoprotein is an intermediate step in the irreversible deposition of extracellular cholesterol in atherosclerotic lesions. Incubation with plasmin allowed maximum release of lipoprotein: plasmin = crude collagenase greater than trypsin greater than \"pure\" collagenase greater than chondroitinase ABC in order of their relative effectiveness. The concentration of immobilized lipoprotein was significantly correlated (r = 0.793; P less than 0.001) with the concentration in the tissue of fibrin or other insoluble derivatives of fibrinogen (\"fibrin\"). In aliquots of lesions incubated with varying amounts of plasmin for varying times there was a constant relation between release of lipoprotein and release of fibrin-degradation products. Together, these findings suggest that the lipoprotein is associated with insoluble \"fibrin\". This appears to be of considerable clinical interest, suggesting a synergism between lipoprotein and fibrinogen in the accumulation of lipid in lesions.", "contents": "The release of an immobilized lipoprotein fraction from atherosclerotic lesions by incubation with plasmin. A large amount of plasma low density lipoprotein is present in human aortic intima, and this can be removed and measured by electrophoresis directly from the minced tissue into an antibody-containing gel. We now find that, in addition to this electrophoretically mobile lipoprotein, there is an immobilized lipoprotein fraction than can be released from lesions by incubation of the tissue sample with plasmin or other proteolytic enzymes after the mobile lipoprotein has been removed. The concentration of immobilized lipoprotein is highly correlated with the concentration of the residual cholesterol (not mobile on electrophoresis) that has accumulated in the tissue (r = 0.702; P less than 0.001). Thus, in normal intima and early gelatinous lesions it is about 15% of the concentration of mobile lipoprotein, whereas in the atheroma lipid layers of fibrous or gelatinous plaques it may be 2 or 3 times greater than the concentration of mobile lipoprotein. This suggests that immobilization of plasma lipoprotein is an intermediate step in the irreversible deposition of extracellular cholesterol in atherosclerotic lesions. Incubation with plasmin allowed maximum release of lipoprotein: plasmin = crude collagenase greater than trypsin greater than \"pure\" collagenase greater than chondroitinase ABC in order of their relative effectiveness. The concentration of immobilized lipoprotein was significantly correlated (r = 0.793; P less than 0.001) with the concentration in the tissue of fibrin or other insoluble derivatives of fibrinogen (\"fibrin\"). In aliquots of lesions incubated with varying amounts of plasmin for varying times there was a constant relation between release of lipoprotein and release of fibrin-degradation products. Together, these findings suggest that the lipoprotein is associated with insoluble \"fibrin\". This appears to be of considerable clinical interest, suggesting a synergism between lipoprotein and fibrinogen in the accumulation of lipid in lesions."}
{"id": "PMID:186080", "title": "Maximal exercise stress testing in normal and hyperlipidemic children.", "content": "Electrocardiographic and cardiovascular responses during maximal exercise were evaluated in 103 normal children and in 82 children with familial hyperlipoproteinemia. The normal and hyperlipidemic children were comparable in regards to age, weight--height index, resting and exercise blood pressures, and maximal working capacity indices. The cohort of 82 hyperlipidemic children included 61 children (29 boys and 32 girls) with well defined \"monogenic\" familial hyperlipoproteinemia. Segmental ST depression on the exercise electrocardiogram occurred in 8 of these 29 boys (27.6%) as compared to 4 of 55 normal boys (7.3%), P less than 0.025 and in 6 of the 32 girls (19%) as compared to 7 of 48 normal girls (14.6%), P greater than 0.1. Segmental ST depression was present in 14 of 61 (23%) children with \"monogenic\" hyperlipoproteinemia, as compared to 11 of 103 (10.75%) normal (x2 = 4.47, P less than 0.05). An assessment of the clinical significance of an abnormal exercise electrocardiogram in male children with \"monogenic\" hyperlipoproteinemia must await the following: (1) two to four decades of observation and study of the development of morbid or mortal coronary disease, or (2) the future development of improved invasive or noninvasive techniques for the early detection of covert coronary occlusive disease. Currently, maximal exercise electrocardiography cannot be contemplated as a useful indicator of eventual premature coronary artery disease in asymptomatic hyperlipidemic children.", "contents": "Maximal exercise stress testing in normal and hyperlipidemic children. Electrocardiographic and cardiovascular responses during maximal exercise were evaluated in 103 normal children and in 82 children with familial hyperlipoproteinemia. The normal and hyperlipidemic children were comparable in regards to age, weight--height index, resting and exercise blood pressures, and maximal working capacity indices. The cohort of 82 hyperlipidemic children included 61 children (29 boys and 32 girls) with well defined \"monogenic\" familial hyperlipoproteinemia. Segmental ST depression on the exercise electrocardiogram occurred in 8 of these 29 boys (27.6%) as compared to 4 of 55 normal boys (7.3%), P less than 0.025 and in 6 of the 32 girls (19%) as compared to 7 of 48 normal girls (14.6%), P greater than 0.1. Segmental ST depression was present in 14 of 61 (23%) children with \"monogenic\" hyperlipoproteinemia, as compared to 11 of 103 (10.75%) normal (x2 = 4.47, P less than 0.05). An assessment of the clinical significance of an abnormal exercise electrocardiogram in male children with \"monogenic\" hyperlipoproteinemia must await the following: (1) two to four decades of observation and study of the development of morbid or mortal coronary disease, or (2) the future development of improved invasive or noninvasive techniques for the early detection of covert coronary occlusive disease. Currently, maximal exercise electrocardiography cannot be contemplated as a useful indicator of eventual premature coronary artery disease in asymptomatic hyperlipidemic children."}
{"id": "PMID:186081", "title": "Serum lipoproteins and atherosclerosis in animals.", "content": "The lipoproteins have been examined in more than 300 serum or plasma samples taken during life or at post mortem from a fairly wide range of mammals, birds and reptiles. The material, which was collected over a period of several years, was subjected to a limited range of lipid analyses, but all specimens were submitted to electrophoresis with paper or cellulose acetate membrane as supporting medium. The lipoprotein pattern in mammals appears to be basically similar to that in man, but there are wide variations in lipid concentrations; the highest levels being found in bears, seals and primates. High concentrations were also observed in many birds and a few reptiles, but the lipoprotein patterns in these vertebrates differ from those in mammals and are further greatly modified by oviparity. Semi-quantitative data on the degree of atherosclerosis were available on the animals that died. There was only a crude positive correlation between the intensity of the arterial disease and high serum beta-lipoprotein levels, and it was concluded that the latter are probably of only secondary importance in the development of spontaneous atherosclerosis in animals.", "contents": "Serum lipoproteins and atherosclerosis in animals. The lipoproteins have been examined in more than 300 serum or plasma samples taken during life or at post mortem from a fairly wide range of mammals, birds and reptiles. The material, which was collected over a period of several years, was subjected to a limited range of lipid analyses, but all specimens were submitted to electrophoresis with paper or cellulose acetate membrane as supporting medium. The lipoprotein pattern in mammals appears to be basically similar to that in man, but there are wide variations in lipid concentrations; the highest levels being found in bears, seals and primates. High concentrations were also observed in many birds and a few reptiles, but the lipoprotein patterns in these vertebrates differ from those in mammals and are further greatly modified by oviparity. Semi-quantitative data on the degree of atherosclerosis were available on the animals that died. There was only a crude positive correlation between the intensity of the arterial disease and high serum beta-lipoprotein levels, and it was concluded that the latter are probably of only secondary importance in the development of spontaneous atherosclerosis in animals."}
{"id": "PMID:186082", "title": "Reconstitution of T cell function in patients with subacute sclerosing panencephalitis treated with thymus humoral factor.", "content": "Two patients with subacute sclerosing panencephalitis (SSPE) showed impairment of cell-mediated immunity, as indicated by a low T cell number, decreased intracellular cyclic AMP levels of peripheral blood lymphocytes, negative graft-vs.-host reaction in vivo, negative skin reactions to common antigens and, in one of the patients, abnormal reactions in migration inhibition factor tests. Since some of the impaired T cell functions in one of the patients were reconstituted in vitro by the administration of thymus humoral factor (THF), a thymic hormone shown in an earlier study to regulate maturation of T lymphocytes in in vitro and in vivo animal models, a course of THF administration was given to both patients in this study. In vitro and in vivo assays, which reflect T cell competence, were performed before and after a daily schedule of THF administration that lasted for 10 days in one patient and 21 days in the other. The results of this preliminary trial suggested that THF was capable of reconstituting the impaired T cell functions in both patients after a short term of treatment. These preliminary results should encourage additional long-term therapeutic trials with THF in SSPE patients with impaired cell-mediated immunity.", "contents": "Reconstitution of T cell function in patients with subacute sclerosing panencephalitis treated with thymus humoral factor. Two patients with subacute sclerosing panencephalitis (SSPE) showed impairment of cell-mediated immunity, as indicated by a low T cell number, decreased intracellular cyclic AMP levels of peripheral blood lymphocytes, negative graft-vs.-host reaction in vivo, negative skin reactions to common antigens and, in one of the patients, abnormal reactions in migration inhibition factor tests. Since some of the impaired T cell functions in one of the patients were reconstituted in vitro by the administration of thymus humoral factor (THF), a thymic hormone shown in an earlier study to regulate maturation of T lymphocytes in in vitro and in vivo animal models, a course of THF administration was given to both patients in this study. In vitro and in vivo assays, which reflect T cell competence, were performed before and after a daily schedule of THF administration that lasted for 10 days in one patient and 21 days in the other. The results of this preliminary trial suggested that THF was capable of reconstituting the impaired T cell functions in both patients after a short term of treatment. These preliminary results should encourage additional long-term therapeutic trials with THF in SSPE patients with impaired cell-mediated immunity."}
{"id": "PMID:186089", "title": "Apha-adrenergic receptor blockade increases human REM sleep.", "content": "1 An alpha-adrenergic receptor blocking agent, thymoxamine (150 mg i.v.) in the early night sleep of young adults increased REM sleep duration and also brief awakenings in the early night, while slow wave sleep, stage 3+4, was diminished. In the later night, however, stage 3+4 sleep was increased. Control experiments demonstrated that thymoxamine (i.v.) was without effect on blood pressure. 2 REM sleep duration may be inversely proportional to noradrenaline available at central alpha-adrenoceptors, but the control mechanisms for REM sleep appear interdependent with those for NREM sleep.", "contents": "Apha-adrenergic receptor blockade increases human REM sleep. 1 An alpha-adrenergic receptor blocking agent, thymoxamine (150 mg i.v.) in the early night sleep of young adults increased REM sleep duration and also brief awakenings in the early night, while slow wave sleep, stage 3+4, was diminished. In the later night, however, stage 3+4 sleep was increased. Control experiments demonstrated that thymoxamine (i.v.) was without effect on blood pressure. 2 REM sleep duration may be inversely proportional to noradrenaline available at central alpha-adrenoceptors, but the control mechanisms for REM sleep appear interdependent with those for NREM sleep."}
{"id": "PMID:186090", "title": "Beta-adrenoceptors in the human dorsal hand vein, and the effects of propranolol and practolol on venous sensitivity to noradrenaline.", "content": "1 Infusion of isoprenaline into dorsal hand veins preconstricted with noradrenaline produced vasodilatation in four subjects out of five which was reversed by addition of propranolol. It is confirmed that beta-adrenoceptors are present in the hand veins of most subjects. 2 Addition of either propranolol or practolol to infusions of vasoconstrictor doses of noradrenaline potentiated the vasoconstriction in the hand vein. 3 After systemic administration of propranolol (0.3 mg/kg) or of practolol (1.0 mg/kg) intravenously, the sensitivity of the hand vein to the vasoconstrictor activity of noradrenaline was increased by 7.5 times and 2.9 times respectively. Significant reductions in hand skin temperature and resting pulse rate occurred after propranolol only. 4 It is suggested that this may be a useful method for the quantitative estimation of peripheral vascular beta-adrenoceptor blocking activity in man. At the doses used, significant beta-adrenoceptor blockade appears to occur at this site with practolol as well as propranolol.", "contents": "Beta-adrenoceptors in the human dorsal hand vein, and the effects of propranolol and practolol on venous sensitivity to noradrenaline. 1 Infusion of isoprenaline into dorsal hand veins preconstricted with noradrenaline produced vasodilatation in four subjects out of five which was reversed by addition of propranolol. It is confirmed that beta-adrenoceptors are present in the hand veins of most subjects. 2 Addition of either propranolol or practolol to infusions of vasoconstrictor doses of noradrenaline potentiated the vasoconstriction in the hand vein. 3 After systemic administration of propranolol (0.3 mg/kg) or of practolol (1.0 mg/kg) intravenously, the sensitivity of the hand vein to the vasoconstrictor activity of noradrenaline was increased by 7.5 times and 2.9 times respectively. Significant reductions in hand skin temperature and resting pulse rate occurred after propranolol only. 4 It is suggested that this may be a useful method for the quantitative estimation of peripheral vascular beta-adrenoceptor blocking activity in man. At the doses used, significant beta-adrenoceptor blockade appears to occur at this site with practolol as well as propranolol."}
{"id": "PMID:186091", "title": "Distant visceral metastases in pleural mesothelioma.", "content": "Distant visceral metastases were found in 15 of 32 cases of pleural mesothelioma (47%). Contrary to earlier reports pleural mesothelioma should be regarded as a tumour in which visceral metastases are not uncommon. No association was found between the histological type of mesothelioma and visceral metastases; the peritoneal involvement found in five cases is probably due to local infiltration and seeding.", "contents": "Distant visceral metastases in pleural mesothelioma. Distant visceral metastases were found in 15 of 32 cases of pleural mesothelioma (47%). Contrary to earlier reports pleural mesothelioma should be regarded as a tumour in which visceral metastases are not uncommon. No association was found between the histological type of mesothelioma and visceral metastases; the peritoneal involvement found in five cases is probably due to local infiltration and seeding."}
{"id": "PMID:186092", "title": "Abnormal fibrin polymerization in liver disease.", "content": "Although there have been isolated reports of an acquired abnormal fibrinogen in patients with liver disease, its frequency and clinical significance is not known. In this study 121 consecutive patients with a wide spectrum of hepatic disorders were screened for abnormal fibrin polymerization. A simple colorimetric method using Reptilase was employed. Of 32 patients with proven cirrhosis, 16 (50%) showed abnormal fibrin polymerization. The incidence in decompensated alcoholic cirrhosis was particularly high. The abnormality was also detected in all patients with acute liver failure and seven of 15 with chronic active liver disease. Clinical improvement often correlated with its disappearance. Two patients with primary liver cell tumours demonstrated the abnormal polymerization. In patients with bleeding oesophageal varices the detection of abnormal fibrin polymerization was associated with a poor prognosis. None of the patients with surgical obstructive jaundice (26) or miscellaneous liver disorders (37) had abnormal fibrin polymerization. The occurrence of abnormal fibrin polymerization in liver disease is more frequent than previously suspected and usually signifies severe primary hepatocellular dysfunction. Evidence is presented to support the presence of a primary abnormality of fibrinogen as the cause of impaired fibrin monomer polymerization.", "contents": "Abnormal fibrin polymerization in liver disease. Although there have been isolated reports of an acquired abnormal fibrinogen in patients with liver disease, its frequency and clinical significance is not known. In this study 121 consecutive patients with a wide spectrum of hepatic disorders were screened for abnormal fibrin polymerization. A simple colorimetric method using Reptilase was employed. Of 32 patients with proven cirrhosis, 16 (50%) showed abnormal fibrin polymerization. The incidence in decompensated alcoholic cirrhosis was particularly high. The abnormality was also detected in all patients with acute liver failure and seven of 15 with chronic active liver disease. Clinical improvement often correlated with its disappearance. Two patients with primary liver cell tumours demonstrated the abnormal polymerization. In patients with bleeding oesophageal varices the detection of abnormal fibrin polymerization was associated with a poor prognosis. None of the patients with surgical obstructive jaundice (26) or miscellaneous liver disorders (37) had abnormal fibrin polymerization. The occurrence of abnormal fibrin polymerization in liver disease is more frequent than previously suspected and usually signifies severe primary hepatocellular dysfunction. Evidence is presented to support the presence of a primary abnormality of fibrinogen as the cause of impaired fibrin monomer polymerization."}
{"id": "PMID:186093", "title": "ACTH levels in amniotic fluid during pregnancy.", "content": "The fetal pituitary-adrenal axis plays an important role in the role in the regulation of fetal development. In order to obtain information about fetal ACTH secretion at different gestational ages, a total of 109 amniotic fluid ACTH determinations was performed by radioimmunoassay. There was a significantly higher level of ACTH during 26 to 30 weeks of pregnancy (429 +/- 180-4 pg/ml) than in early (208-7 +/- 90-6 pg/ml) and in late (172-7 +/- 97-4 pg/ml) pregnancy; fetal sex, uterine contractions and maternal complications in pregnancy did not affect levels. The ACTH level in the first urine of six newborn infants (160-0 +/- 40-6 pg/ml) approximated to that in the amniotic fluid in late pregnancy. Our results support the assumption of a fetal origin for ACTH in amniotic fluid. The high secretion of ACTH at the beginning of the last trimester of pregnancy may stimulate the development of the adrenal cortex and result in the increased cortisol secretion necessary for fetal lung maturation.", "contents": "ACTH levels in amniotic fluid during pregnancy. The fetal pituitary-adrenal axis plays an important role in the role in the regulation of fetal development. In order to obtain information about fetal ACTH secretion at different gestational ages, a total of 109 amniotic fluid ACTH determinations was performed by radioimmunoassay. There was a significantly higher level of ACTH during 26 to 30 weeks of pregnancy (429 +/- 180-4 pg/ml) than in early (208-7 +/- 90-6 pg/ml) and in late (172-7 +/- 97-4 pg/ml) pregnancy; fetal sex, uterine contractions and maternal complications in pregnancy did not affect levels. The ACTH level in the first urine of six newborn infants (160-0 +/- 40-6 pg/ml) approximated to that in the amniotic fluid in late pregnancy. Our results support the assumption of a fetal origin for ACTH in amniotic fluid. The high secretion of ACTH at the beginning of the last trimester of pregnancy may stimulate the development of the adrenal cortex and result in the increased cortisol secretion necessary for fetal lung maturation."}
{"id": "PMID:186094", "title": "Selective interaction of 5'-bromodeoxyuridine substituted DNA with different chromosomal proteins.", "content": "Chromosomal proteins selectively interact with 5'-bromodeoxyuridine (BrdUrd) substituted DNA relative to unsubstituted DNA. The relative affinities of chromosomal proteins for BrdUrd-DNA and unsubstituted DNA were measured by both thermal chromatography on hydroxylapatite and selective retention on nitrocellulose filters. Certain chromosomal proteins have a high affinity for hydroxylapatite; thus, during thermal chromatography of chromatin, the single-stranded DNA component percolates across a bed of adsorbed proteins as it elutes. We have measured the relative affinities of Brd-Urd-DNA and normal DNA for chromosomal proteins by chromatographing appropriate mixtures on hydroxylapatite. The results show that, under these conditions, the histone components, rather than the nonhistone chromatin proteins, retard the BrdUrd-substituted DNA. In addition, the individual histones vary in the degree of their affinity for BrdUrd-DNA in the order H3 greater than H4 greater than H2A greater than H2B greater than H1. We have used the property that protein-DNA complexes have a preferential affinity for nitrocellulose filters over naked DNA to measure the selective binding of BrdUrd-DNA and unsubstituted DNA's to both histone and nonhistone chromosomal proteins at low temperatures. The histones selectively retained BrdUrd-DNA on filters in the order H4 greater than H2A greater than H3 greater than H2B greater than H1. Using this assay, the nonhistones displayed greater selectivity toward BrdUrd-DNA than the histone fraction. We interpret these results to mean BrdUrd-containing DNA has a specific affinity for certain chromosomal proteins with BrdUrd-DNA may be the basis for selective inhibition of cytodifferentiation by the thymidine analogue, BrdUrd.", "contents": "Selective interaction of 5'-bromodeoxyuridine substituted DNA with different chromosomal proteins. Chromosomal proteins selectively interact with 5'-bromodeoxyuridine (BrdUrd) substituted DNA relative to unsubstituted DNA. The relative affinities of chromosomal proteins for BrdUrd-DNA and unsubstituted DNA were measured by both thermal chromatography on hydroxylapatite and selective retention on nitrocellulose filters. Certain chromosomal proteins have a high affinity for hydroxylapatite; thus, during thermal chromatography of chromatin, the single-stranded DNA component percolates across a bed of adsorbed proteins as it elutes. We have measured the relative affinities of Brd-Urd-DNA and normal DNA for chromosomal proteins by chromatographing appropriate mixtures on hydroxylapatite. The results show that, under these conditions, the histone components, rather than the nonhistone chromatin proteins, retard the BrdUrd-substituted DNA. In addition, the individual histones vary in the degree of their affinity for BrdUrd-DNA in the order H3 greater than H4 greater than H2A greater than H2B greater than H1. We have used the property that protein-DNA complexes have a preferential affinity for nitrocellulose filters over naked DNA to measure the selective binding of BrdUrd-DNA and unsubstituted DNA's to both histone and nonhistone chromosomal proteins at low temperatures. The histones selectively retained BrdUrd-DNA on filters in the order H4 greater than H2A greater than H3 greater than H2B greater than H1. Using this assay, the nonhistones displayed greater selectivity toward BrdUrd-DNA than the histone fraction. We interpret these results to mean BrdUrd-containing DNA has a specific affinity for certain chromosomal proteins with BrdUrd-DNA may be the basis for selective inhibition of cytodifferentiation by the thymidine analogue, BrdUrd."}
{"id": "PMID:186095", "title": "Estimation of membrane surface potential and charge density from the phase equilibrium of a paramagnetic amphiphile.", "content": "The distribution of a paramagnetic amphiphile, N,N-dimethyl-N-nonyl-N-tempoylammonium ion, between the membranes of charged phospholipid vesicles and the surrounding aqueous medium was studied by electron paramagnetic resonance spectroscopy. By systematically varying the surface charge of the vesicles and the aqueous electrolyte concentration, the distribution was shown to indicate vesicle surface potential. At each fixed phospholipid composition, the surface potential exhibited a dependence on aqueous NaCl concentration very similar to that predicted by the Gouy equation. The ability to sense and quantitate surface potentials makes this facile and sensitive technique of value in the study of cell and organelle surfaces.", "contents": "Estimation of membrane surface potential and charge density from the phase equilibrium of a paramagnetic amphiphile. The distribution of a paramagnetic amphiphile, N,N-dimethyl-N-nonyl-N-tempoylammonium ion, between the membranes of charged phospholipid vesicles and the surrounding aqueous medium was studied by electron paramagnetic resonance spectroscopy. By systematically varying the surface charge of the vesicles and the aqueous electrolyte concentration, the distribution was shown to indicate vesicle surface potential. At each fixed phospholipid composition, the surface potential exhibited a dependence on aqueous NaCl concentration very similar to that predicted by the Gouy equation. The ability to sense and quantitate surface potentials makes this facile and sensitive technique of value in the study of cell and organelle surfaces."}
{"id": "PMID:186096", "title": "Membrane fluidity change in erythrocytes induced by complement system.", "content": "The structural change in erythrocyte membranes induced by antibody and complement was studied using phospholipid spin-labels. Sheep erythrocytes were labeled with phosphatidylcholine spin-label and various intermediate cells (erythrocyte-antibody complex (EA), EA bound with complement components from C1 to C7 (EAC1-7), EAC1-8, and EAC1-9) were prepared. Electron spin resonance spectra of EA, EAC1-7, and EAC1-8 were very similar to that of the erythrocytes, while that of EAC1-9 was markedly different. The overall splitting value for the lysed EAC1-9 (53 G) was much smaller than that for the erythrocytes (57 G), indicating a marked fluidization around the phosphatidylcholine label. The unlysed EAC1-9 membranes contained a limited fraction of the fluidized area. When EA was reacted with complement in the presence of 36% bovine serum albumin, the membranes were fluidized similarly to the lysed EAC1-9, although the hemolysis was largely blocked. The membranes of unlysed EAC1-9 prepared in isotonic (ethylenedinitrilo)tetraacetic acid were also fluidized, but to somewhat smaller extent. The role of C9 in the modification of erythrocyte membranes was also demonstrated using Mg2+ ghosts, which were prepared by hypotonic hemolysis in the presence of Mg2+. The membranes of Mg2+ ghost of EAC1-7 were markedly fluidized when bound with C8 and C9, but not affected by binding of C8 only. The component C8 was found to give a latent effect on the membranes that caused irreversible fluidization upon osmotic shock. The terminal component thus creates a fluidized area in the erythrocyte membranes through which small ions and molecules may diffuse more easily and the resulting osmotic unbalance may finally cause hemolysis.", "contents": "Membrane fluidity change in erythrocytes induced by complement system. The structural change in erythrocyte membranes induced by antibody and complement was studied using phospholipid spin-labels. Sheep erythrocytes were labeled with phosphatidylcholine spin-label and various intermediate cells (erythrocyte-antibody complex (EA), EA bound with complement components from C1 to C7 (EAC1-7), EAC1-8, and EAC1-9) were prepared. Electron spin resonance spectra of EA, EAC1-7, and EAC1-8 were very similar to that of the erythrocytes, while that of EAC1-9 was markedly different. The overall splitting value for the lysed EAC1-9 (53 G) was much smaller than that for the erythrocytes (57 G), indicating a marked fluidization around the phosphatidylcholine label. The unlysed EAC1-9 membranes contained a limited fraction of the fluidized area. When EA was reacted with complement in the presence of 36% bovine serum albumin, the membranes were fluidized similarly to the lysed EAC1-9, although the hemolysis was largely blocked. The membranes of unlysed EAC1-9 prepared in isotonic (ethylenedinitrilo)tetraacetic acid were also fluidized, but to somewhat smaller extent. The role of C9 in the modification of erythrocyte membranes was also demonstrated using Mg2+ ghosts, which were prepared by hypotonic hemolysis in the presence of Mg2+. The membranes of Mg2+ ghost of EAC1-7 were markedly fluidized when bound with C8 and C9, but not affected by binding of C8 only. The component C8 was found to give a latent effect on the membranes that caused irreversible fluidization upon osmotic shock. The terminal component thus creates a fluidized area in the erythrocyte membranes through which small ions and molecules may diffuse more easily and the resulting osmotic unbalance may finally cause hemolysis."}
{"id": "PMID:186097", "title": "Determination of the hydride transfer stereospecificity of nicotinamide adenine dinucleotide linked oxidoreductases by proton magnetic resonance.", "content": "A facile proton magnetic resonance technique is described for the determination of the coenzyme stereospecificity during hydride transfer reactions catalyzed by pyridine nucleotide dependent oxidoreductases. The reliability of this technique was demonstrated by examining the coenzyme stereospecificity of lactate, malate, and 3-phosphoglycerate dehydrogenases, which are known to be A-stereospecific enzymes, as well as triosephosphate and octopine dehydrogenases, which are known to be B-stereospecific enzymes. Furthermore, by applying this technique, it was shown that the previously unstudied enzymes D-beta-hydroxybutyrate and 4-aminobutanal dehydrogenases are B- and A-stereospecific enzymes, respectively. In addition, the nicotinamide adenine dinucleotide linked reaction of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides was found to be B stereospecific, like the reaction of the nicotinamide adenine dinucleotide phosphate linked yeast enzyme.", "contents": "Determination of the hydride transfer stereospecificity of nicotinamide adenine dinucleotide linked oxidoreductases by proton magnetic resonance. A facile proton magnetic resonance technique is described for the determination of the coenzyme stereospecificity during hydride transfer reactions catalyzed by pyridine nucleotide dependent oxidoreductases. The reliability of this technique was demonstrated by examining the coenzyme stereospecificity of lactate, malate, and 3-phosphoglycerate dehydrogenases, which are known to be A-stereospecific enzymes, as well as triosephosphate and octopine dehydrogenases, which are known to be B-stereospecific enzymes. Furthermore, by applying this technique, it was shown that the previously unstudied enzymes D-beta-hydroxybutyrate and 4-aminobutanal dehydrogenases are B- and A-stereospecific enzymes, respectively. In addition, the nicotinamide adenine dinucleotide linked reaction of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides was found to be B stereospecific, like the reaction of the nicotinamide adenine dinucleotide phosphate linked yeast enzyme."}
{"id": "PMID:186098", "title": "Substrate binding properties of converting enzyme using a series of p-nitrophenylalanyl derivatives of angiotensin I.", "content": "The binding properties of angiotensin I for the active site of rabbit lung converting enzyme (CE) have been investigated. A series of angiotensin I like substrates, all containing the C-terminal tripeptide, (NO2)Phe-His-Leu, were synthesized by increasing the length of the peptide at the N-terminal end. A total of eight peptides were studied, the largest being [Asn1, (NO2)Phe8]angiotensin I. As determined by thin-layer chromatography, all substrates were hydrolyzed only at the (NO2)Phe-His bond by purified converting enzyme, with the release of the dipeptide, His-Leu. By using an absorbance increase upon hydrolysis, the Michaelis constants and velocity maxima were determined and used to estimate those amino acids in the angiotensin I molecule that contribute significantly to binding to converting enzyme. It was hypothesized that, upon addition or substitution of one or more amino acids to the N-terminal end, a proportional decrease in both KM and Vm is needed in order to conclude that the substrate actually increases its affinity for the enzyme. A test of the proportionality for the variation of KM and Vm was found to be positive for all the substrates, except the N-terminal carbobenzoxy-blocked tripeptide, Z(NO2)Phe-His-Leu. Substitutions near the bond that is hydrolyzed (e.g., proline for the carbobenzoxy group) appear to alter the catalytic properties of CE, while additions far removed from the site of hydrolysis (e.g., the N-terminal tripeptide Asn-Arg-Val) may enhance binding affinity.", "contents": "Substrate binding properties of converting enzyme using a series of p-nitrophenylalanyl derivatives of angiotensin I. The binding properties of angiotensin I for the active site of rabbit lung converting enzyme (CE) have been investigated. A series of angiotensin I like substrates, all containing the C-terminal tripeptide, (NO2)Phe-His-Leu, were synthesized by increasing the length of the peptide at the N-terminal end. A total of eight peptides were studied, the largest being [Asn1, (NO2)Phe8]angiotensin I. As determined by thin-layer chromatography, all substrates were hydrolyzed only at the (NO2)Phe-His bond by purified converting enzyme, with the release of the dipeptide, His-Leu. By using an absorbance increase upon hydrolysis, the Michaelis constants and velocity maxima were determined and used to estimate those amino acids in the angiotensin I molecule that contribute significantly to binding to converting enzyme. It was hypothesized that, upon addition or substitution of one or more amino acids to the N-terminal end, a proportional decrease in both KM and Vm is needed in order to conclude that the substrate actually increases its affinity for the enzyme. A test of the proportionality for the variation of KM and Vm was found to be positive for all the substrates, except the N-terminal carbobenzoxy-blocked tripeptide, Z(NO2)Phe-His-Leu. Substitutions near the bond that is hydrolyzed (e.g., proline for the carbobenzoxy group) appear to alter the catalytic properties of CE, while additions far removed from the site of hydrolysis (e.g., the N-terminal tripeptide Asn-Arg-Val) may enhance binding affinity."}
{"id": "PMID:186099", "title": "Characterization of procollagen synthesized by matrix-free cells isolated from chick embryo tendons.", "content": "The genetic type and molecular structure of the precursor forms of collagen synthesized by matrix-free tendon cells isolated from 17-day old chick embryos were examined by chromatographic and electrophoretic techniques. The [14C]proline-labeled collagenous proteins secreted by the cells resolved on diethylaminoethylcellulose into two peaks, A and B. Both peaks contained type I collagenous proteins since on chromatography on carboxymethylcellulose, after limited pepsin proteolysis, both peaks contained alpha1 and alpha2 chains of collagen in a 2:1 ratio, and cyanogen bromide peptide maps of the 14C-labeled protein in both peaks were similar to cyanogen bromide peptide maps derived from authentic type I collagen. Enzymatic digestion with purified mammalian collagenase demonstrated that the collagen precursor in peak B contained noncollagenous peptide extensions at both the amino- and carboxy-terminal ends of the molecule, while peak A had only carboxy-terminal extension peptides. Although both the amino- and carboxy-terminal extensions incorporated radioactive cystine, only the carboxy-terminal extensions contained interchain disulfide bonds. The carboxy-terminal extensions were also shown to incorporate radioactive tryptophan. Since most of the precursor forms of collagen recovered in the incubation medium chromatographed in peak B, it is concluded that matrix-free tendon cells secrete only type I procollagen with extension peptides at both the amino- and carboxy-terminal ends of the molecule.", "contents": "Characterization of procollagen synthesized by matrix-free cells isolated from chick embryo tendons. The genetic type and molecular structure of the precursor forms of collagen synthesized by matrix-free tendon cells isolated from 17-day old chick embryos were examined by chromatographic and electrophoretic techniques. The [14C]proline-labeled collagenous proteins secreted by the cells resolved on diethylaminoethylcellulose into two peaks, A and B. Both peaks contained type I collagenous proteins since on chromatography on carboxymethylcellulose, after limited pepsin proteolysis, both peaks contained alpha1 and alpha2 chains of collagen in a 2:1 ratio, and cyanogen bromide peptide maps of the 14C-labeled protein in both peaks were similar to cyanogen bromide peptide maps derived from authentic type I collagen. Enzymatic digestion with purified mammalian collagenase demonstrated that the collagen precursor in peak B contained noncollagenous peptide extensions at both the amino- and carboxy-terminal ends of the molecule, while peak A had only carboxy-terminal extension peptides. Although both the amino- and carboxy-terminal extensions incorporated radioactive cystine, only the carboxy-terminal extensions contained interchain disulfide bonds. The carboxy-terminal extensions were also shown to incorporate radioactive tryptophan. Since most of the precursor forms of collagen recovered in the incubation medium chromatographed in peak B, it is concluded that matrix-free tendon cells secrete only type I procollagen with extension peptides at both the amino- and carboxy-terminal ends of the molecule."}
{"id": "PMID:186100", "title": "A transition state analogue for two pyruvate metabolizing enzymes, lactate dehydrogenase and alanine dehydrogenase.", "content": "The synthesis of 5-(2-oxalylethyl)-NADH, a reduced nicotinamide adenine dinucleotide (NADH) derivate with pyruvate covalently attached to the 5 position of the dihydronicotinamide ring over an additional methylene group has been described previously (Trommer, W.E., Blume, H., and Kapmeyer, H. (1976) Justus Liebigs Ann. Chem., 848). In the presence of lactate dehydrogenase, the dihydropyridine ring of this coenzyme-substrate analogue is oxidized and the carbonyl function of the side chain is reduced to the corresponding L-hydroxy derivative with a maximum velocity of 1/3000 of the natural reaction. This reaction is intramolecular as shown by competition experiments with pyruvate. 5-(2-oxalylethyl)-NADH (pyr-NADH) appears to be a true transition state analogue, proving its postulated structure. Pyr-NADH is high specific for this enzyme as demonstrated by the facts that (1) D-lactate dehydrogenase does not catalyze the intramolecular redox reaction, although the substrate moiety of pyr-NADH is reduced in the presence of NADH; (2) when tested with malate dehydrogenase, alcohol dehydrogenase, glyceraldehyde phosphate dehydrogenase,glycerate dehydrogenase, and glycerol dehydrogenase pyr-NADH is not even oxidized in the presence of the corresponding substrates. However, a great similarity between the transition states of the reduction of pyruvate catalyzed by lactate dehydrogenase and alanine dehydrogenase could be shown. Alanine dehydrogenase catalyzes the intramolecular redox reaction as well. In the presence of ammonium ions, pyr-NADH is transformed to 5-(3-carboxyl-3-aminopropyl)-NAD+.", "contents": "A transition state analogue for two pyruvate metabolizing enzymes, lactate dehydrogenase and alanine dehydrogenase. The synthesis of 5-(2-oxalylethyl)-NADH, a reduced nicotinamide adenine dinucleotide (NADH) derivate with pyruvate covalently attached to the 5 position of the dihydronicotinamide ring over an additional methylene group has been described previously (Trommer, W.E., Blume, H., and Kapmeyer, H. (1976) Justus Liebigs Ann. Chem., 848). In the presence of lactate dehydrogenase, the dihydropyridine ring of this coenzyme-substrate analogue is oxidized and the carbonyl function of the side chain is reduced to the corresponding L-hydroxy derivative with a maximum velocity of 1/3000 of the natural reaction. This reaction is intramolecular as shown by competition experiments with pyruvate. 5-(2-oxalylethyl)-NADH (pyr-NADH) appears to be a true transition state analogue, proving its postulated structure. Pyr-NADH is high specific for this enzyme as demonstrated by the facts that (1) D-lactate dehydrogenase does not catalyze the intramolecular redox reaction, although the substrate moiety of pyr-NADH is reduced in the presence of NADH; (2) when tested with malate dehydrogenase, alcohol dehydrogenase, glyceraldehyde phosphate dehydrogenase,glycerate dehydrogenase, and glycerol dehydrogenase pyr-NADH is not even oxidized in the presence of the corresponding substrates. However, a great similarity between the transition states of the reduction of pyruvate catalyzed by lactate dehydrogenase and alanine dehydrogenase could be shown. Alanine dehydrogenase catalyzes the intramolecular redox reaction as well. In the presence of ammonium ions, pyr-NADH is transformed to 5-(3-carboxyl-3-aminopropyl)-NAD+."}
{"id": "PMID:186101", "title": "Pulmonary angiotensin-converting enzyme antienzyme antibody.", "content": "A method has been developed for quantitating anticatalytic activity in antibody preparations made in goats against pure solubilized angiotensin-converting enzyme from rabbit pulmonary membranes. Anticatalytic activity was purified about 90-fold from a single batch of serum by a procedure including diethylaminoethylcellulose chromatography and elution from Sepharose columns containing covalently bound pure enzyme. Antiholoenzyme antibody was fractionated with respect to charge and binding affinity; however, these different populations each inhibited enzymatic hydrolysis of hippurylhistidylleucine, angiotensin I, and bradykinin. The inhibition dose-response curves were similar for hydrolysis of hippurylhistidylleucine and angiotensin I despite the difference in molecular weight of these substrates. Evidence is presented suggesting that a single molecule of antibody can bind two molecules of enzyme and that at least 18% of the total antiholoenzyme antibody population is directed against determinants which influence catalytic activity. A competitive immunoassay was developed with radioiodinated pulmonary enzyme as displaceable antigen. The anticatalytic and radioimmune assays were used to examine immunological properties of converting enzymes in various rabbit organs and fluids. Kidney, brain, and serum were found to contain converting enzymes which were immunologically identified with that in rabbit lung. Converting enzyme in seminal plasma was similar to the lung enzyme in the anticatalytic assay, but showed lower immunoreactivity in the radioimmune assay.", "contents": "Pulmonary angiotensin-converting enzyme antienzyme antibody. A method has been developed for quantitating anticatalytic activity in antibody preparations made in goats against pure solubilized angiotensin-converting enzyme from rabbit pulmonary membranes. Anticatalytic activity was purified about 90-fold from a single batch of serum by a procedure including diethylaminoethylcellulose chromatography and elution from Sepharose columns containing covalently bound pure enzyme. Antiholoenzyme antibody was fractionated with respect to charge and binding affinity; however, these different populations each inhibited enzymatic hydrolysis of hippurylhistidylleucine, angiotensin I, and bradykinin. The inhibition dose-response curves were similar for hydrolysis of hippurylhistidylleucine and angiotensin I despite the difference in molecular weight of these substrates. Evidence is presented suggesting that a single molecule of antibody can bind two molecules of enzyme and that at least 18% of the total antiholoenzyme antibody population is directed against determinants which influence catalytic activity. A competitive immunoassay was developed with radioiodinated pulmonary enzyme as displaceable antigen. The anticatalytic and radioimmune assays were used to examine immunological properties of converting enzymes in various rabbit organs and fluids. Kidney, brain, and serum were found to contain converting enzymes which were immunologically identified with that in rabbit lung. Converting enzyme in seminal plasma was similar to the lung enzyme in the anticatalytic assay, but showed lower immunoreactivity in the radioimmune assay."}
{"id": "PMID:186102", "title": "Adenosine and adenine nucleotides stimulation of skin (epidermal) adenylate cyclase.", "content": "Adenosine, AMP, ADP and ATP activated adenylate cyclase in pig skin (epidermis) slices resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of the cyclic AMP-phosphodiesterase inhibitor, papaverine. But another inhibitor, theophylline, strongly blocked the activation of adenylate cyclase by adenosine and adenine nucleotides. Theophylline apparently competed with adenosine for the cell surface receptor. Like theophylline, the addition of adenine alone caused no accumulation of cyclic AMP, but it significantly inhibited the stimulatory effect of adenosine. Guanosine, or guanine, cytidine, uridine, or thymidine nucleotides had no effect on the accumulation of cyclic AMP. Among other adenine nucleotides we tested, adenosine 5'-monophosphoramidate, but not adenosine 5'-monosulfate significantly increased cyclic AMP especially with the addition of papaverine. Neither 2'- nor 3'-adenylic acid were effective. Our data indicate that pig epidermis has four specific and independent adenylate cyclase systems for adenosine (and adenine nucleotides), histamine, epinephrine and prostaglandin E.", "contents": "Adenosine and adenine nucleotides stimulation of skin (epidermal) adenylate cyclase. Adenosine, AMP, ADP and ATP activated adenylate cyclase in pig skin (epidermis) slices resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of the cyclic AMP-phosphodiesterase inhibitor, papaverine. But another inhibitor, theophylline, strongly blocked the activation of adenylate cyclase by adenosine and adenine nucleotides. Theophylline apparently competed with adenosine for the cell surface receptor. Like theophylline, the addition of adenine alone caused no accumulation of cyclic AMP, but it significantly inhibited the stimulatory effect of adenosine. Guanosine, or guanine, cytidine, uridine, or thymidine nucleotides had no effect on the accumulation of cyclic AMP. Among other adenine nucleotides we tested, adenosine 5'-monophosphoramidate, but not adenosine 5'-monosulfate significantly increased cyclic AMP especially with the addition of papaverine. Neither 2'- nor 3'-adenylic acid were effective. Our data indicate that pig epidermis has four specific and independent adenylate cyclase systems for adenosine (and adenine nucleotides), histamine, epinephrine and prostaglandin E."}
{"id": "PMID:186103", "title": "Effect of cold exposure on phosphoenolpyruvate carboxykinase (GTP) activity and cyclic amp concentration in livers of starved rats. Role of glucorticoids.", "content": "The effect of cold exposure (5 degrees C) on the concentration of cyclic AMP and on the activity of phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) was investigated in the liver of intact and adrenalectomized starved rats. Intact starved rats responded to cold exposure with a large increase in  both the concentration of hepatic cyclic AMP and the activity of phosphoenolpyruvate carboxykinase above the starvation level. Adrenalectomy did not impair the cold-induced maximum elevation of cyclic AMP but totally prevented the response of the enzyme to cold. Yet, this response was completely restored by hydrocortisone treatment, while the steroid per se had no effect on enzyme activity. In isolated perfused livers of intact starved rats dibutyryl cyclic AMP provoked an immediate dramatic increase in phosphoenolpyruvate carboxykinase activity above the starvation level even if mRNA synthesis was inhibited by cordycepin. However, cyclic AMP was ineffective in increasing enzyme activity in livers of adrenalectomized rats. From these results it is suggested (i) that in starved rats the adaptation to the enhanced glucose demand provoked by cold exposure includes the induction of hepatic phosphoenolpyruvate carboxykinase above the starvation level, (ii) that this induction is due to the cold-induced increase in hepatic cyclic AMP levels, (iii) that cyclic AMP stimulates enzyme synthesis at a post-transcriptional step and (iv) that the cold-induced cyclic AMP-mediated induction of phosphoenolpyruvate carboxykinase above the starvation level requires the \"permissive\" effect of glucocorticoids.", "contents": "Effect of cold exposure on phosphoenolpyruvate carboxykinase (GTP) activity and cyclic amp concentration in livers of starved rats. Role of glucorticoids. The effect of cold exposure (5 degrees C) on the concentration of cyclic AMP and on the activity of phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.32) was investigated in the liver of intact and adrenalectomized starved rats. Intact starved rats responded to cold exposure with a large increase in  both the concentration of hepatic cyclic AMP and the activity of phosphoenolpyruvate carboxykinase above the starvation level. Adrenalectomy did not impair the cold-induced maximum elevation of cyclic AMP but totally prevented the response of the enzyme to cold. Yet, this response was completely restored by hydrocortisone treatment, while the steroid per se had no effect on enzyme activity. In isolated perfused livers of intact starved rats dibutyryl cyclic AMP provoked an immediate dramatic increase in phosphoenolpyruvate carboxykinase activity above the starvation level even if mRNA synthesis was inhibited by cordycepin. However, cyclic AMP was ineffective in increasing enzyme activity in livers of adrenalectomized rats. From these results it is suggested (i) that in starved rats the adaptation to the enhanced glucose demand provoked by cold exposure includes the induction of hepatic phosphoenolpyruvate carboxykinase above the starvation level, (ii) that this induction is due to the cold-induced increase in hepatic cyclic AMP levels, (iii) that cyclic AMP stimulates enzyme synthesis at a post-transcriptional step and (iv) that the cold-induced cyclic AMP-mediated induction of phosphoenolpyruvate carboxykinase above the starvation level requires the \"permissive\" effect of glucocorticoids."}
{"id": "PMID:186104", "title": "Effect of substance P and eledoisin on K+ efflux, amylase release and cyclic nucleotide levels in slices of rat parotid gland.", "content": "The undecapeptides, substance P and eledoisin, caused a rapid, concentration-dependent increase in K+ efflux and amylase release from parotid tissue slices. The effects were not blocked by beta-adrenergic, alpha-adrenergic, or cholinergic antagonists. Incubation buffer calcium was required for stimulation of K efflux and amylase release. The action of the undecapepides was independent of any effects on parotid cyclic AMP or cyclic GMP levels. Since the actions of the undecapeptides were Ca2+ dependent and no effects on cyclic nucleotide levels were discerned it was concluded that Ca2+ plays a primary role in agonist regulation of K+ efflux from the parotid.", "contents": "Effect of substance P and eledoisin on K+ efflux, amylase release and cyclic nucleotide levels in slices of rat parotid gland. The undecapeptides, substance P and eledoisin, caused a rapid, concentration-dependent increase in K+ efflux and amylase release from parotid tissue slices. The effects were not blocked by beta-adrenergic, alpha-adrenergic, or cholinergic antagonists. Incubation buffer calcium was required for stimulation of K efflux and amylase release. The action of the undecapepides was independent of any effects on parotid cyclic AMP or cyclic GMP levels. Since the actions of the undecapeptides were Ca2+ dependent and no effects on cyclic nucleotide levels were discerned it was concluded that Ca2+ plays a primary role in agonist regulation of K+ efflux from the parotid."}
{"id": "PMID:186105", "title": "Effect of high level section of the spinal cord on the cyclic AMP system in rat liver.", "content": "The effect of high level section of the spinal cord upon the hepatic cyclic AMP system was investigated in the rat. We report that transection of the spinal cord dramatically decreases the basal level of cyclic AMP from 0.88 nmol/g liver to 0.36 nmol/g at 1 h and to 0.20 nmol/g at 4 h. This was not due to increased activity of cyclic AMP phosphodiesterase or to decreased activity of basal adenylate cyclase. The sensitivity of adenylate cyclase to its usual effectors in vitro was not impaired. It is proposed that the lowering of liver cyclic AMP below its basal level after high level section of the spinal cord is due to decreased levels of hepatic catecholamines and/or plasma glucagon.", "contents": "Effect of high level section of the spinal cord on the cyclic AMP system in rat liver. The effect of high level section of the spinal cord upon the hepatic cyclic AMP system was investigated in the rat. We report that transection of the spinal cord dramatically decreases the basal level of cyclic AMP from 0.88 nmol/g liver to 0.36 nmol/g at 1 h and to 0.20 nmol/g at 4 h. This was not due to increased activity of cyclic AMP phosphodiesterase or to decreased activity of basal adenylate cyclase. The sensitivity of adenylate cyclase to its usual effectors in vitro was not impaired. It is proposed that the lowering of liver cyclic AMP below its basal level after high level section of the spinal cord is due to decreased levels of hepatic catecholamines and/or plasma glucagon."}
{"id": "PMID:186106", "title": "Separation and characterization of two distinct hemagglutinins contained in purified leukocytosis-promoting factor from Bordetella pertussis.", "content": "1. The leukocytosis-promoting factor of Bordetella pertussis was found to contain two hemagglutinins with different susceptibilities to papain and separable from each other by agarose gel filtration with Tris - HCl buffer containing 1 M NaCl. 2. One hemagglutinin, referred to as hemagglutinin HA, had a high hemagglutinating activity, but neither leukocytosis-promoting nor histamine-sensitizing activity. The other hemagglutinin, referred to as hemagglutinin LPF appeared to be identical with the leukocytosis-promoting factor and possessed a low hemagglutinating and high leukocytosis-promoting and histamine-sensitizing activities. 3. The hemagglutinating activity of hemagglutinin HA was highly sensitive to papain. The hemagglutinating, leukocytosis-promoting, and histamine-sensitizing activities of hemagglutinin LPF were fairly resistant to the enzyme. 4. The two hemagglutinins were distinct from each other in immunological and chemical properties. 5. Morphologically, hemagglutinin HA showed itself to be filamentous molecules of approx. 2 X 40 nm, while hemagglutinin LPF comprised of spherical molecules of approx. 6 nm diameter. 6. The molecular weight values of hemagglutinin HA estimated by sodium dodecylsulfate polyacrylamide gel electrophoresis and sucrose density gradient centrifugation were approx. 126 000 and 133 000, respectively. Those of hemagglutinin LPF estimated by polyacrylamide gel electrophoreis at pH 4.5, sucrose density gradient centrifugation and gel filtration on a 10% agarose column were 107 000, 103 000 and 30 000, respectively. A possible reason for obtaining such a low molecular weight value by gel filtration is discussed.", "contents": "Separation and characterization of two distinct hemagglutinins contained in purified leukocytosis-promoting factor from Bordetella pertussis. 1. The leukocytosis-promoting factor of Bordetella pertussis was found to contain two hemagglutinins with different susceptibilities to papain and separable from each other by agarose gel filtration with Tris - HCl buffer containing 1 M NaCl. 2. One hemagglutinin, referred to as hemagglutinin HA, had a high hemagglutinating activity, but neither leukocytosis-promoting nor histamine-sensitizing activity. The other hemagglutinin, referred to as hemagglutinin LPF appeared to be identical with the leukocytosis-promoting factor and possessed a low hemagglutinating and high leukocytosis-promoting and histamine-sensitizing activities. 3. The hemagglutinating activity of hemagglutinin HA was highly sensitive to papain. The hemagglutinating, leukocytosis-promoting, and histamine-sensitizing activities of hemagglutinin LPF were fairly resistant to the enzyme. 4. The two hemagglutinins were distinct from each other in immunological and chemical properties. 5. Morphologically, hemagglutinin HA showed itself to be filamentous molecules of approx. 2 X 40 nm, while hemagglutinin LPF comprised of spherical molecules of approx. 6 nm diameter. 6. The molecular weight values of hemagglutinin HA estimated by sodium dodecylsulfate polyacrylamide gel electrophoresis and sucrose density gradient centrifugation were approx. 126 000 and 133 000, respectively. Those of hemagglutinin LPF estimated by polyacrylamide gel electrophoreis at pH 4.5, sucrose density gradient centrifugation and gel filtration on a 10% agarose column were 107 000, 103 000 and 30 000, respectively. A possible reason for obtaining such a low molecular weight value by gel filtration is discussed."}
{"id": "PMID:186107", "title": "Moenomycin: an inhibitor of c55-isoprenoid-alcohol kinase from Staphylococcus aureus.", "content": "The effect of a variety of structurally diverse antibiotics on C55-isoprenoid-alcohol kinase (EC 2.7.1.66) from Staphylococcus aureus has been examined. Only moenomycin was found to be inhibitory (Ki = 0.2 mM). Moenocinol, the C25 lipid component of moenomycin, did not serve as a substrate of the kinase reaction and was less inhibitory than the intact antibiotic. It is concluded that the observed inhibition may be due to the structural similarity between C55-isoprenylmonophosphate and the substituted moenocinol moiety of moenomycin.", "contents": "Moenomycin: an inhibitor of c55-isoprenoid-alcohol kinase from Staphylococcus aureus. The effect of a variety of structurally diverse antibiotics on C55-isoprenoid-alcohol kinase (EC 2.7.1.66) from Staphylococcus aureus has been examined. Only moenomycin was found to be inhibitory (Ki = 0.2 mM). Moenocinol, the C25 lipid component of moenomycin, did not serve as a substrate of the kinase reaction and was less inhibitory than the intact antibiotic. It is concluded that the observed inhibition may be due to the structural similarity between C55-isoprenylmonophosphate and the substituted moenocinol moiety of moenomycin."}
{"id": "PMID:186108", "title": "Subcellular localization of gamma-glutamyl carboxypeptidase and of folates.", "content": "The subcellular distributions of glutamyl carboxypeptidase, folate specific activities, and radioactive metabolites of injected [3H] folic acid were studied in rat liver. The specific activity of glutamyl carboxypeptidase in the lysosomal fraction was near or greater than four times that in the other subcellular fractions. The specific activity of folates was highest in the soluble fraction (102 ng folate/mg protein) and lowest in the microsomal fraction (22 ng folate/mg protein). Nuclear, mitochondrial, and lysosomal folates were 95% folate polyglutamates, and microsomal and soluble folates were 85--90% folate polyglutamates. Injected [3H] folic acid was initially concentrated in the microsomal fraction, as measured by 3h cpm per ng folate. Initially, injected [3H] folic acid was found converted to folate penta- and hexaglutamates in all fractions to a similar extent except in the microsomes where the percentage conversion was much less, as measured by the percentage of total 3H cpm determined to be [3H] folate penta- and hexaglutamates. At 24 h, the conversion of [3H] folates to penta- and hexaglutamates in each fraction was less than that found for the endogenous folates. Injected [3H] folic acid after 2h was found to consist of 94% reduced folates in the soluble fraction, 56% in the mitochondrial, 55% in the nuclear, 20% in the lysosomal, and 15% in the microsomal fraction.", "contents": "Subcellular localization of gamma-glutamyl carboxypeptidase and of folates. The subcellular distributions of glutamyl carboxypeptidase, folate specific activities, and radioactive metabolites of injected [3H] folic acid were studied in rat liver. The specific activity of glutamyl carboxypeptidase in the lysosomal fraction was near or greater than four times that in the other subcellular fractions. The specific activity of folates was highest in the soluble fraction (102 ng folate/mg protein) and lowest in the microsomal fraction (22 ng folate/mg protein). Nuclear, mitochondrial, and lysosomal folates were 95% folate polyglutamates, and microsomal and soluble folates were 85--90% folate polyglutamates. Injected [3H] folic acid was initially concentrated in the microsomal fraction, as measured by 3h cpm per ng folate. Initially, injected [3H] folic acid was found converted to folate penta- and hexaglutamates in all fractions to a similar extent except in the microsomes where the percentage conversion was much less, as measured by the percentage of total 3H cpm determined to be [3H] folate penta- and hexaglutamates. At 24 h, the conversion of [3H] folates to penta- and hexaglutamates in each fraction was less than that found for the endogenous folates. Injected [3H] folic acid after 2h was found to consist of 94% reduced folates in the soluble fraction, 56% in the mitochondrial, 55% in the nuclear, 20% in the lysosomal, and 15% in the microsomal fraction."}
{"id": "PMID:186109", "title": "A Limulus glucose-6-phosphatase with phosphotransferase activity characteristic of vertebrate liver microsomes. Its possible evolutionary significance.", "content": "1. Limulus hepatopancreas, coxal glands and intestine contain a particulate enzyme which can synthesize glucose 6-phosphate from glucose and inorganic pyrophosphate or carbamyl phosphate as well as hydrolyze glucose 6-phosphate. This has been clearly differentiated from hydrolysis by lysosomal or soluble phosphatases. 2. The enzyme resembles vertebrate glucose-6-phosphatase in its specific anatomical distribution, pH optimum, kinetic properties, donor specificity and phospholipid dependence, as indicated by its satency and lability to detergent treatment. 3. A variety of other invertebrates tested exhibited little or no PPi-glucose phosphotransferase activity with these properties. A similar phosphotransferase activity of lobster hepatopancreas had somewhat different kinetic properties and pH optimum. 4. The hypothesis that a specific glucose-6-phosphatase is to be found only in those animals which utilize free glucose as an important circulating form of energy is presented and discussed. It appears that a variety of transport compounds, such as trehalose and glucose, was tried at the evolutionary level of the Arthropods.", "contents": "A Limulus glucose-6-phosphatase with phosphotransferase activity characteristic of vertebrate liver microsomes. Its possible evolutionary significance. 1. Limulus hepatopancreas, coxal glands and intestine contain a particulate enzyme which can synthesize glucose 6-phosphate from glucose and inorganic pyrophosphate or carbamyl phosphate as well as hydrolyze glucose 6-phosphate. This has been clearly differentiated from hydrolysis by lysosomal or soluble phosphatases. 2. The enzyme resembles vertebrate glucose-6-phosphatase in its specific anatomical distribution, pH optimum, kinetic properties, donor specificity and phospholipid dependence, as indicated by its satency and lability to detergent treatment. 3. A variety of other invertebrates tested exhibited little or no PPi-glucose phosphotransferase activity with these properties. A similar phosphotransferase activity of lobster hepatopancreas had somewhat different kinetic properties and pH optimum. 4. The hypothesis that a specific glucose-6-phosphatase is to be found only in those animals which utilize free glucose as an important circulating form of energy is presented and discussed. It appears that a variety of transport compounds, such as trehalose and glucose, was tried at the evolutionary level of the Arthropods."}
{"id": "PMID:186111", "title": "The use of affinity chromatography in purification of cyclic nucleotide receptor proteins.", "content": "Biospecific affinity chromatography has been used to purify specific cyclic AMP and cyclic GMP receptor proteins. Several variables are important for successful purification of the cyclic AMP receptor protein, the most critical being the length of the aliphatic spacer side arm. 8-(2-Aminoethyl)-amino-cyclic AMP coupled to the aliphatic spacer side arm. 8-(2-Aminoethyl)-amino-cyclic AMP coupled to agarose specifically retains the cyclic AMP receptor protein by interaction with the immobilized nucleotide. Binding of the cyclic AMP receptor subunit of cyclic AMP-dependent protein kinase to the immobilized nucleotide results in dissociation of the catalytic protein phosphokinase subunit which is not retained. The retained cyclic AMP receptor protein is subsequently eluted by cyclic AMP. Homogeneous cyclic AMP receptor protein prepared from rabbit skeletal muscle by affinity chromatography has been characterized. The molecular weight of the native protein as determined by analytical ultracentrifugation and polyacrylamide gel electrophoresis at varying acrylamide concentrations is 76 800 and 82 000, respectively. The protein is asymmetric with frictional and axial ratios of 1.64 and 12. SDS and urea polyacrylamide gel electrophoresis indicate that the native cyclic AMP receptor is composed of two identical subunits of 42 700 molecular weight. The native protein dimer binds 2 moles of cyclic AMP per mole of protein and is active in suppressing activity of isolated catalytic subunits of cyclic AMP-dependent protein kinase. Cyclic GMP receptor protein from bovine lung has been purified using the same affinity chromatography media. Since cyclic nucleotide binding to cyclic GMP-dependent protein kinase does not result in dissociation of regulatory receptor and catalytic phosphotransferase subunits, the cyclic GMP-dependent protein kinase holoenzyme is retained on the column and can be subsequently specifically eluted with cyclic GMP.", "contents": "The use of affinity chromatography in purification of cyclic nucleotide receptor proteins. Biospecific affinity chromatography has been used to purify specific cyclic AMP and cyclic GMP receptor proteins. Several variables are important for successful purification of the cyclic AMP receptor protein, the most critical being the length of the aliphatic spacer side arm. 8-(2-Aminoethyl)-amino-cyclic AMP coupled to the aliphatic spacer side arm. 8-(2-Aminoethyl)-amino-cyclic AMP coupled to agarose specifically retains the cyclic AMP receptor protein by interaction with the immobilized nucleotide. Binding of the cyclic AMP receptor subunit of cyclic AMP-dependent protein kinase to the immobilized nucleotide results in dissociation of the catalytic protein phosphokinase subunit which is not retained. The retained cyclic AMP receptor protein is subsequently eluted by cyclic AMP. Homogeneous cyclic AMP receptor protein prepared from rabbit skeletal muscle by affinity chromatography has been characterized. The molecular weight of the native protein as determined by analytical ultracentrifugation and polyacrylamide gel electrophoresis at varying acrylamide concentrations is 76 800 and 82 000, respectively. The protein is asymmetric with frictional and axial ratios of 1.64 and 12. SDS and urea polyacrylamide gel electrophoresis indicate that the native cyclic AMP receptor is composed of two identical subunits of 42 700 molecular weight. The native protein dimer binds 2 moles of cyclic AMP per mole of protein and is active in suppressing activity of isolated catalytic subunits of cyclic AMP-dependent protein kinase. Cyclic GMP receptor protein from bovine lung has been purified using the same affinity chromatography media. Since cyclic nucleotide binding to cyclic GMP-dependent protein kinase does not result in dissociation of regulatory receptor and catalytic phosphotransferase subunits, the cyclic GMP-dependent protein kinase holoenzyme is retained on the column and can be subsequently specifically eluted with cyclic GMP."}
{"id": "PMID:186112", "title": "Protein components in the very low density lipoproteins of hen's egg yolks. Identification of highly aggregating (gelling) and less aggregating (non-gelling) proteins.", "content": "Apoproteins of hen's egg yolk very low density lipoprotein has been separated by Sephadex G-200 gel filtration in 0.5% sodium dodecyl sulfate into three categories of proteins termed apoprotein A, apoprotein B and apoprotein C. Apoprotein A fraction consists of several aggregated proteins (linked possibly by -S-S- bridges) as shown by acrylamide gel electrophoresis in the presence of 2-mercaptoethanol. Apoprotein B contains two major protein components, B1 and B2, with molecular weights of 78 000 and 64 000, respectively, and two minor proteins components. Apoprotein C was obtained in a pure form as a low molecular weight, -S-S- linked dimer protein and accounted for about 30% of the total protein. In the monomeric form, apoprotein C has a molecular weight of 9400. Apoprotein A and apoprotein B have similar amino acid composition, except in isoleucine content which is over two times in apoprotein B as compared to apoprotein A. Apoprotein C lacks histidine and is richer in arginine than apoproteins A or B. Apoprotein C has lysine as N-terminal, while apoproteins A and B have predominantly arginine as the N-terminal amino acid. All the three fractions contain carbohydrate residues, apoprotein B being the richest in carbohydrate content. Cold-stored apoproteins A forms a clear gel when dispersed in 0.5% sodium dodecyl sulfate at concentration of above 2 mg/ml, while apoprotein B forms a gel only above 10 mg/ml. Apoprotein C, even at 35 mg/ml, forms a clear solution with no tendency to gel.", "contents": "Protein components in the very low density lipoproteins of hen's egg yolks. Identification of highly aggregating (gelling) and less aggregating (non-gelling) proteins. Apoproteins of hen's egg yolk very low density lipoprotein has been separated by Sephadex G-200 gel filtration in 0.5% sodium dodecyl sulfate into three categories of proteins termed apoprotein A, apoprotein B and apoprotein C. Apoprotein A fraction consists of several aggregated proteins (linked possibly by -S-S- bridges) as shown by acrylamide gel electrophoresis in the presence of 2-mercaptoethanol. Apoprotein B contains two major protein components, B1 and B2, with molecular weights of 78 000 and 64 000, respectively, and two minor proteins components. Apoprotein C was obtained in a pure form as a low molecular weight, -S-S- linked dimer protein and accounted for about 30% of the total protein. In the monomeric form, apoprotein C has a molecular weight of 9400. Apoprotein A and apoprotein B have similar amino acid composition, except in isoleucine content which is over two times in apoprotein B as compared to apoprotein A. Apoprotein C lacks histidine and is richer in arginine than apoproteins A or B. Apoprotein C has lysine as N-terminal, while apoproteins A and B have predominantly arginine as the N-terminal amino acid. All the three fractions contain carbohydrate residues, apoprotein B being the richest in carbohydrate content. Cold-stored apoproteins A forms a clear gel when dispersed in 0.5% sodium dodecyl sulfate at concentration of above 2 mg/ml, while apoprotein B forms a gel only above 10 mg/ml. Apoprotein C, even at 35 mg/ml, forms a clear solution with no tendency to gel."}
{"id": "PMID:186113", "title": "Electron paramagnetic resonance of Hb St Louis beta28 (B10) Leu replaced by Gln.", "content": "Hemoglobin St Louis beta28 (B10) Leu replaced by Gln is a new mutant which occurs as a natural valency hybrid (alpha2beta+2), or hemoglobin M (Cohen-Solal, M., Seligmann, M., Thillet, J. and Rosa, J. (1973) FEBS Lett. 33, 37-41). The electron paramagnetic resonance (EPR) spectrum of native Hb St Louis at pH 6.2 shows a mixture of three species. Two are high spin, one with tetragonal symmetry, like Hb+ A, the other with rhombic distortion. The third is a low-spin form corresponding to a hemichrome with the distal (E7) histidine as the sixth ligand of the ferric iron. The hemichrome is also found in red blood cells. After oxidation to the alpha+2beta+2 form, three EPR species are seen. Surprisingly, there remains only one high-spin signal, with almost tetragonal symmetry. Besides the low-spin hemichrome, a hydroxy signal is observed even at pH 6.2. These observations imply interactions between the alpha and beta hemes.", "contents": "Electron paramagnetic resonance of Hb St Louis beta28 (B10) Leu replaced by Gln. Hemoglobin St Louis beta28 (B10) Leu replaced by Gln is a new mutant which occurs as a natural valency hybrid (alpha2beta+2), or hemoglobin M (Cohen-Solal, M., Seligmann, M., Thillet, J. and Rosa, J. (1973) FEBS Lett. 33, 37-41). The electron paramagnetic resonance (EPR) spectrum of native Hb St Louis at pH 6.2 shows a mixture of three species. Two are high spin, one with tetragonal symmetry, like Hb+ A, the other with rhombic distortion. The third is a low-spin form corresponding to a hemichrome with the distal (E7) histidine as the sixth ligand of the ferric iron. The hemichrome is also found in red blood cells. After oxidation to the alpha+2beta+2 form, three EPR species are seen. Surprisingly, there remains only one high-spin signal, with almost tetragonal symmetry. Besides the low-spin hemichrome, a hydroxy signal is observed even at pH 6.2. These observations imply interactions between the alpha and beta hemes."}
{"id": "PMID:186114", "title": "Function of three cytochromes in photosynthesis of whole cells of Rhodospirillum rubrum as studied by flash spectroscopy. Evidence for two types of reaction center.", "content": "1. Changes in the absorption spectrum induced by 10-mus flashes and continuous light of various intensities were studied in whole cells of Rhodospirillum rubrum in the presence and absence of 2-n-heptyl-4-hydroxyquinoline-N-oxide(HOQNO) and antimycin A. 2. Three cytochromes, c-420 (cytochrome c2), c-560 (cytochrome b) and c-428 were photoactive and gamma and alpha peaks at 420 and 550, 428 and 560, and 428 and 551 nm, respectively; they were photooxidized following the flash with half times of 0.3, 0.6 and 7 ms in the approximate ratios of 1/100, 1/300 and 1/1000 (cytochrome oxidized/antenna chlorophyll) and became reduced with half times of 12 ms, 60 ms and 0.7 s, respectively. c-428 and c-560 have not been distinguished before. 3. From a detailed analysis of the kinetics of P+ (oxidized reaction center chlorophyll) and the cytochromes, we conclude that 5% of the P+ (P2+) oxidizes c-428, whereas the remaining 95% of P+ (P1+) oxidizes c-420. At actinic light intensities low enough to keep c-420 fully reduced, approx. 4-5% of P becomes oxidized, accompanied by all c-428. The P2+ -P2 difference spectrum induced by this weak light is, when corrected for a shift to longer wavelengths of the bacteriochlorophyll absorption band at 878 nm, identical to the difference spectrum caused by the photooxidation of the remaining P1. At low flash intensity, c-428 becomes preferentially photooxidized, which suggests that the reaction centers where c-428 functions as a secondary donor contain much more antenna pigments compared to the centers where c-420 serves this purpose. 4. c+-420 is reduced in a competitive way by reduced c-560 (t 1/2=7 ms), and by an electron donor pool, (t 1/2=15 ms). HOQNO inhibits both pathways; antimycin A only the first. In the presence of HOQNO, c-560 is in the oxidized state in the dark, and is reduced in a light flash (t 1/2=100 ms), indicating that c-560 acts in a cyclic electron transport chain connected to P1. 5. The ratio of numbers of molecules P1 and antenna bacteriochlorophyll, transferring excitation energy to P1, is P1/bacteriochlorophyll1=1/30 P2: bacteriochlorophyll2=1/300; c-420/P1=1:2; c-560/P1=1/6; C-428/P2=1/1; bacteriochlorophyll2=7:3. If P2 is oxidized, excitation energy is transferred from bacteriochlorophyll2 to bacteriochlorophyll1.", "contents": "Function of three cytochromes in photosynthesis of whole cells of Rhodospirillum rubrum as studied by flash spectroscopy. Evidence for two types of reaction center. 1. Changes in the absorption spectrum induced by 10-mus flashes and continuous light of various intensities were studied in whole cells of Rhodospirillum rubrum in the presence and absence of 2-n-heptyl-4-hydroxyquinoline-N-oxide(HOQNO) and antimycin A. 2. Three cytochromes, c-420 (cytochrome c2), c-560 (cytochrome b) and c-428 were photoactive and gamma and alpha peaks at 420 and 550, 428 and 560, and 428 and 551 nm, respectively; they were photooxidized following the flash with half times of 0.3, 0.6 and 7 ms in the approximate ratios of 1/100, 1/300 and 1/1000 (cytochrome oxidized/antenna chlorophyll) and became reduced with half times of 12 ms, 60 ms and 0.7 s, respectively. c-428 and c-560 have not been distinguished before. 3. From a detailed analysis of the kinetics of P+ (oxidized reaction center chlorophyll) and the cytochromes, we conclude that 5% of the P+ (P2+) oxidizes c-428, whereas the remaining 95% of P+ (P1+) oxidizes c-420. At actinic light intensities low enough to keep c-420 fully reduced, approx. 4-5% of P becomes oxidized, accompanied by all c-428. The P2+ -P2 difference spectrum induced by this weak light is, when corrected for a shift to longer wavelengths of the bacteriochlorophyll absorption band at 878 nm, identical to the difference spectrum caused by the photooxidation of the remaining P1. At low flash intensity, c-428 becomes preferentially photooxidized, which suggests that the reaction centers where c-428 functions as a secondary donor contain much more antenna pigments compared to the centers where c-420 serves this purpose. 4. c+-420 is reduced in a competitive way by reduced c-560 (t 1/2=7 ms), and by an electron donor pool, (t 1/2=15 ms). HOQNO inhibits both pathways; antimycin A only the first. In the presence of HOQNO, c-560 is in the oxidized state in the dark, and is reduced in a light flash (t 1/2=100 ms), indicating that c-560 acts in a cyclic electron transport chain connected to P1. 5. The ratio of numbers of molecules P1 and antenna bacteriochlorophyll, transferring excitation energy to P1, is P1/bacteriochlorophyll1=1/30 P2: bacteriochlorophyll2=1/300; c-420/P1=1:2; c-560/P1=1/6; C-428/P2=1/1; bacteriochlorophyll2=7:3. If P2 is oxidized, excitation energy is transferred from bacteriochlorophyll2 to bacteriochlorophyll1."}
{"id": "PMID:186115", "title": "Ligand-induced spectral changes in cytochrome c oxidase and their possible significance.", "content": "1. The spectral shifts induced on the binding of H2S to ferric cytochrome aa3 are similar to those induced by cyanide, reflecting a possible high- to low-spin state change in the a3 haem. Opposite shifts are seen with either formate or low azide concentrations, while high azide concentrations reverse the change induced at lower concentrations. The unusually high Soret band in the half-reduced sulphide-inhibited species (a2+a33+H2S) results from the superposition of cytochrome a2+ and cytochrome a33+H2S peaks. 2. The difference spectra in the visible region for cytochrome a2+ minus cytochrome a3+ obtained with four inhibitors (cytochrome a2+ a3+I minus minus a3+a33+I)are similar, except that azide and sulphide induce blue shifts of the alpha-peak. The trough in the Soret region for the azide complex is much deeper than that for the other complexes, suggesting changes in the cytochrome a33+HN3 centre on reduction of cytochrome a. 3. The \"oxygenated\" and \"high-energy\" forms of cytochrome aa3 both involve spectral changes at the a3 haem similar to the changes induced by cyanide and sulphide. The spectrum of partially reduced cytochrome aa3 in the presence of reductant and oxygen indicates the steady-state occurrence of appreciable levels of low-spin (oxygenated) cytochrome aa3. These may be important for energy conservation during the action of cytochrome aa3 in the intact mitochondrial membrane.", "contents": "Ligand-induced spectral changes in cytochrome c oxidase and their possible significance. 1. The spectral shifts induced on the binding of H2S to ferric cytochrome aa3 are similar to those induced by cyanide, reflecting a possible high- to low-spin state change in the a3 haem. Opposite shifts are seen with either formate or low azide concentrations, while high azide concentrations reverse the change induced at lower concentrations. The unusually high Soret band in the half-reduced sulphide-inhibited species (a2+a33+H2S) results from the superposition of cytochrome a2+ and cytochrome a33+H2S peaks. 2. The difference spectra in the visible region for cytochrome a2+ minus cytochrome a3+ obtained with four inhibitors (cytochrome a2+ a3+I minus minus a3+a33+I)are similar, except that azide and sulphide induce blue shifts of the alpha-peak. The trough in the Soret region for the azide complex is much deeper than that for the other complexes, suggesting changes in the cytochrome a33+HN3 centre on reduction of cytochrome a. 3. The \"oxygenated\" and \"high-energy\" forms of cytochrome aa3 both involve spectral changes at the a3 haem similar to the changes induced by cyanide and sulphide. The spectrum of partially reduced cytochrome aa3 in the presence of reductant and oxygen indicates the steady-state occurrence of appreciable levels of low-spin (oxygenated) cytochrome aa3. These may be important for energy conservation during the action of cytochrome aa3 in the intact mitochondrial membrane."}
{"id": "PMID:186116", "title": "Oxidative phosphorylation properties of mitochondria isolated from transplanted hepatoma.", "content": "Mitochondria were isolated from Morris hepatomas with rapid (types 3683, 7777, and 3924A) and intermediate (types 5123D and 7800) growth rates, using proteolytic digestion of minced tumor tissue to release the particles. Mitochondria isolated by the same procedure from rat liver were employed as controls. All the hepatoma mitochondria were capable of coupled respiration with normal phosphorylation yields (ADP/O) and respiratory control ratios ranging from 2 to considerably more than 10. Particles from hepatomas 7777 and 7800 exhibited properties closest to liver mitochondria, while those from hepatomas 3683 and 3924A showed the greatest difference. All the hepatoma mitochondria were capable of oxidizing succinate, 3-hydroxybutyrate and monoamines. However, the oxidation rates of the latter two substrates by mitochondria from hepatomas 3683 and 3924A were only a fraction of the control rates. These differences appeared to be due, at least in part, to the structural instability of the isolated hepatoma mitochondria. In contrast to the reports of others, all hepatoma mitochondria exhibited considerable stimulation of ATPase activity by uncouplers. Maximal stimulation of ATPase activity by representatives of three classes of uncouplers was in all instances comparable to the values obtained for rat liver mitochondria.", "contents": "Oxidative phosphorylation properties of mitochondria isolated from transplanted hepatoma. Mitochondria were isolated from Morris hepatomas with rapid (types 3683, 7777, and 3924A) and intermediate (types 5123D and 7800) growth rates, using proteolytic digestion of minced tumor tissue to release the particles. Mitochondria isolated by the same procedure from rat liver were employed as controls. All the hepatoma mitochondria were capable of coupled respiration with normal phosphorylation yields (ADP/O) and respiratory control ratios ranging from 2 to considerably more than 10. Particles from hepatomas 7777 and 7800 exhibited properties closest to liver mitochondria, while those from hepatomas 3683 and 3924A showed the greatest difference. All the hepatoma mitochondria were capable of oxidizing succinate, 3-hydroxybutyrate and monoamines. However, the oxidation rates of the latter two substrates by mitochondria from hepatomas 3683 and 3924A were only a fraction of the control rates. These differences appeared to be due, at least in part, to the structural instability of the isolated hepatoma mitochondria. In contrast to the reports of others, all hepatoma mitochondria exhibited considerable stimulation of ATPase activity by uncouplers. Maximal stimulation of ATPase activity by representatives of three classes of uncouplers was in all instances comparable to the values obtained for rat liver mitochondria."}
{"id": "PMID:186117", "title": "A quench-flow kinetic investigation of calcium ion accumulation by isolated cardiac sarcoplasmic reticulum. Dependence of initial velocity on free calcium ion concentration and influence of preincubation with a protein kinase, MgATP, and cyclic AMP.", "content": "Ca2+ accumulation at pH 6.8 by isolated rabbit heart microsomes derived chiefly from sarcoplasmic reticulum was investigated by a quench-flow technique. The reaction was terminated at preset times by addition to the reaction mixture of an equal volume of 10 to 50 mM ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid buffered at pH 6.0. The initial velocity of Ca2+ accumulation by microsomal preparations exhibiting a steady state Ca2+ accumulation of 25.6 nmol Ca2+/mg increased from 3.67 to 33.4 nmol Ca2+/mg - s as the free Ca2+ concentration was raised from 0.2 to 18.9 muM. Preincubation of the cardiac microsomes with a partly purified soluble cardiac cyclic AMP-dependent protein kinase, MgATP, and cyclic AMP lead to a significant increase in the initial Ca2+ accumulation rate. The amounts of Ca2+ that were found to accumulate in the first 200 ms of the reaction are comparable to the quantities of the ion that according to literature data need to be removed from the myofilaments and the myoplasm for induction of relaxation of the myocardial fibers.", "contents": "A quench-flow kinetic investigation of calcium ion accumulation by isolated cardiac sarcoplasmic reticulum. Dependence of initial velocity on free calcium ion concentration and influence of preincubation with a protein kinase, MgATP, and cyclic AMP. Ca2+ accumulation at pH 6.8 by isolated rabbit heart microsomes derived chiefly from sarcoplasmic reticulum was investigated by a quench-flow technique. The reaction was terminated at preset times by addition to the reaction mixture of an equal volume of 10 to 50 mM ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid buffered at pH 6.0. The initial velocity of Ca2+ accumulation by microsomal preparations exhibiting a steady state Ca2+ accumulation of 25.6 nmol Ca2+/mg increased from 3.67 to 33.4 nmol Ca2+/mg - s as the free Ca2+ concentration was raised from 0.2 to 18.9 muM. Preincubation of the cardiac microsomes with a partly purified soluble cardiac cyclic AMP-dependent protein kinase, MgATP, and cyclic AMP lead to a significant increase in the initial Ca2+ accumulation rate. The amounts of Ca2+ that were found to accumulate in the first 200 ms of the reaction are comparable to the quantities of the ion that according to literature data need to be removed from the myofilaments and the myoplasm for induction of relaxation of the myocardial fibers."}
{"id": "PMID:186118", "title": "Studies on pulmonary surfactant. Effects of cortisol administration to fetal rabbits on lung phospholipid content, composition and biosynthesis.", "content": "Corticosteroids are known to accelerate maturation of the fetal lung and production of surfactant. We examined the effect of cortisol administration to fetal rabbits on the phospholipid content and composition of lung lavage and lung tissue, as well as on the activities of enzymes involved in the synthesis of phosphatidylcholine and phosphatidylglycerol, the major surface-active components of surfactant. Cortisol was administered by intrauterine injection at 25 days' gestation and the fetuses were delivered at 27 days (full term, 31 days). Saline-injected fetuses, littermates of the cortisol-treated as well as non-littermates, were used as controls. The amount of phospholipid in lung lavage from the hormone-treated fetuses was almost double that of the saline-injected controls and was similar to that of an untreated fetus of more than 30 days' gestation. Similarly, the phospholipid composition of lung lavage from the hormone-treated fetuses was similar to that of an untreated fetus at a greater gestational age. These data, therefore, suggest that cortisol acts by accelerating physiological development. Cortisol administratration stimulated the activity of cholinephosphate cytidylyltransferase and lysolecithin acyltransferase to a small, but statistically significant extent. This is also consistent with an acceleration of normal development. The stimulation of lysolecithin acyltransferase is of interest, since this enzyme is believed to be involved in the synthesis of dipalmitoylglycerophosphocholine, the major surface-active species of phosphatidylcholine. Cortisol administration had no effect on the activities of pulmonary choline kinase, cholinephosphotransferase, lysophosphatidic acid acyltransferase and glycerolphosphate phosphatidyltranferase,  although we have previously shown the latter enzyme to be stimulated following a longer period of exposure to the hormone. Saline injection produced some maturational effects presumably as a result of stress, which may be mediated by corticosteroids or other hormones.", "contents": "Studies on pulmonary surfactant. Effects of cortisol administration to fetal rabbits on lung phospholipid content, composition and biosynthesis. Corticosteroids are known to accelerate maturation of the fetal lung and production of surfactant. We examined the effect of cortisol administration to fetal rabbits on the phospholipid content and composition of lung lavage and lung tissue, as well as on the activities of enzymes involved in the synthesis of phosphatidylcholine and phosphatidylglycerol, the major surface-active components of surfactant. Cortisol was administered by intrauterine injection at 25 days' gestation and the fetuses were delivered at 27 days (full term, 31 days). Saline-injected fetuses, littermates of the cortisol-treated as well as non-littermates, were used as controls. The amount of phospholipid in lung lavage from the hormone-treated fetuses was almost double that of the saline-injected controls and was similar to that of an untreated fetus of more than 30 days' gestation. Similarly, the phospholipid composition of lung lavage from the hormone-treated fetuses was similar to that of an untreated fetus at a greater gestational age. These data, therefore, suggest that cortisol acts by accelerating physiological development. Cortisol administratration stimulated the activity of cholinephosphate cytidylyltransferase and lysolecithin acyltransferase to a small, but statistically significant extent. This is also consistent with an acceleration of normal development. The stimulation of lysolecithin acyltransferase is of interest, since this enzyme is believed to be involved in the synthesis of dipalmitoylglycerophosphocholine, the major surface-active species of phosphatidylcholine. Cortisol administration had no effect on the activities of pulmonary choline kinase, cholinephosphotransferase, lysophosphatidic acid acyltransferase and glycerolphosphate phosphatidyltranferase,  although we have previously shown the latter enzyme to be stimulated following a longer period of exposure to the hormone. Saline injection produced some maturational effects presumably as a result of stress, which may be mediated by corticosteroids or other hormones."}
{"id": "PMID:186119", "title": "The effects of dietary fat and cholesterol on the metabolism of plasma low density lipoprotein apoproteins in squirrel monkeys.", "content": "Low density lipoprotein apoproteins from squirrel monkeys (Saimiri sciureus) had characteristic 2-phase die-away curves in plasma. The kinetic constants were similar with three methods of labeling: in vitro with 125I by the iodine monochloride or the Bolton-Hunter methods or in vivo by the injection of [3H]-leucine into a donor animal. Dietary cholesterol and the type of dietary fat influenced the concentration of plasma cholesterol and low density lipoproteins. The fractional turnover of low density lipoprotein apoprotein was greaterin monkeys fed semipurified diets with safflower oil than in those on butter but was not influenced by dietary cholesterol. The total low density lipoprotein apoprotein turnover (the product of fractional turnover and plasma lipoprotein concentration) was highest in monkeys fed butter plus added cholesterol and lowest in those on safflower oil without cholesterol. Dietary safflower oil resulted in a smaller proportion of the total low density lipoprotein pool in the intravascular compartment than did butter, regardless of whether cholesterol was added.", "contents": "The effects of dietary fat and cholesterol on the metabolism of plasma low density lipoprotein apoproteins in squirrel monkeys. Low density lipoprotein apoproteins from squirrel monkeys (Saimiri sciureus) had characteristic 2-phase die-away curves in plasma. The kinetic constants were similar with three methods of labeling: in vitro with 125I by the iodine monochloride or the Bolton-Hunter methods or in vivo by the injection of [3H]-leucine into a donor animal. Dietary cholesterol and the type of dietary fat influenced the concentration of plasma cholesterol and low density lipoproteins. The fractional turnover of low density lipoprotein apoprotein was greaterin monkeys fed semipurified diets with safflower oil than in those on butter but was not influenced by dietary cholesterol. The total low density lipoprotein apoprotein turnover (the product of fractional turnover and plasma lipoprotein concentration) was highest in monkeys fed butter plus added cholesterol and lowest in those on safflower oil without cholesterol. Dietary safflower oil resulted in a smaller proportion of the total low density lipoprotein pool in the intravascular compartment than did butter, regardless of whether cholesterol was added."}
{"id": "PMID:186120", "title": "Effect of cyclic AMP on glycogen phosphorylase in Coprinus macrorhizus.", "content": "Glycogen phosphorylase (1,4-alpha-D-glucan:orthophosphate alpha-glucosyltransfase, EC 2.4.1.1) activity was found in mycelial extracts of Coprinus macrorhizus concurrently with decrease of glycogen content in mycelial cells. Incubation of the enzyme sample with cyclic AMP and ATP leads to a 3-fold activation of the glucogen phosphorylase activity. Activation of the enzyme partially purified through Sepharose 6B required a cellular fraction containing cyclic AMP-dependent protein kinase.", "contents": "Effect of cyclic AMP on glycogen phosphorylase in Coprinus macrorhizus. Glycogen phosphorylase (1,4-alpha-D-glucan:orthophosphate alpha-glucosyltransfase, EC 2.4.1.1) activity was found in mycelial extracts of Coprinus macrorhizus concurrently with decrease of glycogen content in mycelial cells. Incubation of the enzyme sample with cyclic AMP and ATP leads to a 3-fold activation of the glucogen phosphorylase activity. Activation of the enzyme partially purified through Sepharose 6B required a cellular fraction containing cyclic AMP-dependent protein kinase."}
{"id": "PMID:186121", "title": "Solubilization of angiotensin I-coverting enzyme from rabbit lung using trypsin treatment.", "content": "The solubilization of angiotensin I-converting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1) from rabbit lung was carried out using trypsin treatment. A good recovery of 76% was obtained. The enzyme from solubilized fraction was purified using colums of Sephadex G-200, hydroxyapatite and DEAE-cellulose. The purified enzyme was shown to convert angiotensin I to angiotensin II and also to inactivate bradykinin. The specific activity of the enzyme was 24.3 units/mg protein for hippurylhistidylleucyl hydroxide and 0.182 mumol/min per mg protein for angiotensin I. The enzymic activity obtained after trypsin treatment for 5 h could be divided into two components: (i) an enzyme of molecular weight 300 000 (peak II) and (ii) an enzyme of molecular weight 145 000 (peak III), by Sephadex G-200 gel filtration. The molecular weight of the denatured enzyme was found to be 155 000 by disc gel electrophoresis in the presence of sodium dodecyl sulfate. Km values of peak II and peak III fraction for Hippuryl-His Leu-OH were 2.6 mM.", "contents": "Solubilization of angiotensin I-coverting enzyme from rabbit lung using trypsin treatment. The solubilization of angiotensin I-converting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1) from rabbit lung was carried out using trypsin treatment. A good recovery of 76% was obtained. The enzyme from solubilized fraction was purified using colums of Sephadex G-200, hydroxyapatite and DEAE-cellulose. The purified enzyme was shown to convert angiotensin I to angiotensin II and also to inactivate bradykinin. The specific activity of the enzyme was 24.3 units/mg protein for hippurylhistidylleucyl hydroxide and 0.182 mumol/min per mg protein for angiotensin I. The enzymic activity obtained after trypsin treatment for 5 h could be divided into two components: (i) an enzyme of molecular weight 300 000 (peak II) and (ii) an enzyme of molecular weight 145 000 (peak III), by Sephadex G-200 gel filtration. The molecular weight of the denatured enzyme was found to be 155 000 by disc gel electrophoresis in the presence of sodium dodecyl sulfate. Km values of peak II and peak III fraction for Hippuryl-His Leu-OH were 2.6 mM."}
{"id": "PMID:186122", "title": "Polymeric collagen fibrils. An example of substrate-mediated steric obstruction of enzymic digestion.", "content": "Polymeric collagen fibrils have been reacted with fluorescein and rhodamine isothiocyanates to produce fluorescent dye-labelled fibrils, containing seven dye substituents per molecule of tropocollagen within the polymeric collagen fibrils. Two dye-labelled peptides per molecule of tropocollagen were solubilised by trypsin (EC 3.4.21.4) from the telopeptide regions and four dye-labelled peptides were located in the helical regions solubilised by bacterial collagenase (EC 3.4.24.3). The solubilisation of dye-labelled peptides from these insoluble substrates were employed to measure the kinetics of trypsin and collagenase digestion of the telopeptide and helical regions, respectively, of the insoluble polymeric collagen fibrils. These studies demonstrated an apparent excess of enzyme for the readily available substrate under conditions when it was known that a vast excess of substrate existed in the reaction mixture calculated in terms of a molecular ratio. A point of equivalence was established for both trypsin and bacterial collagenase, approximately one enzyme molecule per 870 substrate molecules. On either side of this point the quantity of products formed was controlled by either the enzyme concentration or the substrate concentration. The results can be explained in terms of the inaccessibility of tropocollagen molecules within the molecular architecture of the polymeric collagen fibrils. The external layer of tropocollagen molecules obstruct collagenolytic enzymes penetrating to, and forming enzyme-substrate complexes with, the bulk of the substrate within the interior of the fibrils.", "contents": "Polymeric collagen fibrils. An example of substrate-mediated steric obstruction of enzymic digestion. Polymeric collagen fibrils have been reacted with fluorescein and rhodamine isothiocyanates to produce fluorescent dye-labelled fibrils, containing seven dye substituents per molecule of tropocollagen within the polymeric collagen fibrils. Two dye-labelled peptides per molecule of tropocollagen were solubilised by trypsin (EC 3.4.21.4) from the telopeptide regions and four dye-labelled peptides were located in the helical regions solubilised by bacterial collagenase (EC 3.4.24.3). The solubilisation of dye-labelled peptides from these insoluble substrates were employed to measure the kinetics of trypsin and collagenase digestion of the telopeptide and helical regions, respectively, of the insoluble polymeric collagen fibrils. These studies demonstrated an apparent excess of enzyme for the readily available substrate under conditions when it was known that a vast excess of substrate existed in the reaction mixture calculated in terms of a molecular ratio. A point of equivalence was established for both trypsin and bacterial collagenase, approximately one enzyme molecule per 870 substrate molecules. On either side of this point the quantity of products formed was controlled by either the enzyme concentration or the substrate concentration. The results can be explained in terms of the inaccessibility of tropocollagen molecules within the molecular architecture of the polymeric collagen fibrils. The external layer of tropocollagen molecules obstruct collagenolytic enzymes penetrating to, and forming enzyme-substrate complexes with, the bulk of the substrate within the interior of the fibrils."}
{"id": "PMID:186123", "title": "Coenzyme B-12-dependent reactions. Part IV. Observations on the purification of ethanolamine ammonia-lyase.", "content": "Purification of ethanolamine ammonia-lyase (EC 4.3.1.7) from a Clostridium sp. grown at the University of Sussex, U.K. and the National Institutes of Health, U.S.A., has been compared and an improved isotopic assay for the enzyme has been developed. Successful purification of this enzyme from Sussex-grown cells requires modification of the published procedure (Kaplan and Stadtman (1968) J. Biol, Chem. 243, 1787-1793) principally a 70% decrease in volume during precipitation with 0.4 M NaCl. This modification also increases the yield from N.I.H.-grown cells. Purified enzyme, resolved of inactive cobalamins, has the same high specific activity from both sources and behaves in the same way on disc gel electrophoresis. Sussex enzyme, before resolution, has less than 20% of the specific activity of unresolved N.I.H. enzyme and contains over 50% more inactive cobalamin. The bound cobalamin from both preparations has been identified as a \"base-on\" Co11 psi-cobalamin.", "contents": "Coenzyme B-12-dependent reactions. Part IV. Observations on the purification of ethanolamine ammonia-lyase. Purification of ethanolamine ammonia-lyase (EC 4.3.1.7) from a Clostridium sp. grown at the University of Sussex, U.K. and the National Institutes of Health, U.S.A., has been compared and an improved isotopic assay for the enzyme has been developed. Successful purification of this enzyme from Sussex-grown cells requires modification of the published procedure (Kaplan and Stadtman (1968) J. Biol, Chem. 243, 1787-1793) principally a 70% decrease in volume during precipitation with 0.4 M NaCl. This modification also increases the yield from N.I.H.-grown cells. Purified enzyme, resolved of inactive cobalamins, has the same high specific activity from both sources and behaves in the same way on disc gel electrophoresis. Sussex enzyme, before resolution, has less than 20% of the specific activity of unresolved N.I.H. enzyme and contains over 50% more inactive cobalamin. The bound cobalamin from both preparations has been identified as a \"base-on\" Co11 psi-cobalamin."}
{"id": "PMID:186124", "title": "Nitrogenase IX. Effect of the MgATP generator on the catalytic and EPR properties of the enzyme in vitro.", "content": "Nitrogenase(nitrogen:(acceptor) oxidoreduction, EC 1.7.99.2) of Clostridium pasteuranium is very sensitive to the ratio of MgADP/MgATP in dithionite oxidation assays. Variation of concentration of creatine kinase, an ATP-regenerating enzyme, can be used to control the ratio of ADP/ATP and thereby the dithionite oxidation activity of nitrogenase. The in vitro properties of nitrogenase support the suggestion of Haaker (Haaker, H., deKok, A. and Veeger, C. (1974) Biochim. Biophys. Acta 357, 344-357) that in vivo the nucleotide ratio and not the electron supply normally regulates nitrogenase activity. In EPR experiments it has been shown that the \"steady state\" varies as a function of the concentration of creatine kinase. The spectral differences are interpreted as being a function of the ratio of MgADP/MgATP obtained in the pseudo steady-state condition, which occurs as a result of variation in relative rates of ATP-utilizing and ATP-generating reactions, that is, the relative nitrogenase and creatine kinase activities. Implications of these finding for interpretation of previously reported kinetic and EPR studies are discussed.", "contents": "Nitrogenase IX. Effect of the MgATP generator on the catalytic and EPR properties of the enzyme in vitro. Nitrogenase(nitrogen:(acceptor) oxidoreduction, EC 1.7.99.2) of Clostridium pasteuranium is very sensitive to the ratio of MgADP/MgATP in dithionite oxidation assays. Variation of concentration of creatine kinase, an ATP-regenerating enzyme, can be used to control the ratio of ADP/ATP and thereby the dithionite oxidation activity of nitrogenase. The in vitro properties of nitrogenase support the suggestion of Haaker (Haaker, H., deKok, A. and Veeger, C. (1974) Biochim. Biophys. Acta 357, 344-357) that in vivo the nucleotide ratio and not the electron supply normally regulates nitrogenase activity. In EPR experiments it has been shown that the \"steady state\" varies as a function of the concentration of creatine kinase. The spectral differences are interpreted as being a function of the ratio of MgADP/MgATP obtained in the pseudo steady-state condition, which occurs as a result of variation in relative rates of ATP-utilizing and ATP-generating reactions, that is, the relative nitrogenase and creatine kinase activities. Implications of these finding for interpretation of previously reported kinetic and EPR studies are discussed."}
{"id": "PMID:186125", "title": "The effect of oxygen concentration on the steady-state kinetics of the solubilized cytochrome c oxidase.", "content": "1. The steady-state kinetics of ascorbate oxidation as a function of oxygen concentration was measured with a solubilized cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) preparation. 2. Linear double reciprocal plots were obtained at various fixed concentrations of ascrobate, cytochrome c and cytochrome aa3. 3. The results are interpreted in terms of an oxidase model similar to that put forward by Minnaert in 1961 (Minnaert, K. (1961) Biochim. Biophys. Acta 50, 23-34). 4. The Km for oxygen at infinite cytochrome c concentration is 0.95 muM and the intramolecular rate constant for the transfer of electrons from cytochrome c to cytochome aa3 is 400 s(-1). According to the model, this implies that the second order rate constant for the reaction between oxygen and the oxidase is 9.5 X 10(7)M(-1)-s(-1).", "contents": "The effect of oxygen concentration on the steady-state kinetics of the solubilized cytochrome c oxidase. 1. The steady-state kinetics of ascorbate oxidation as a function of oxygen concentration was measured with a solubilized cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) preparation. 2. Linear double reciprocal plots were obtained at various fixed concentrations of ascrobate, cytochrome c and cytochrome aa3. 3. The results are interpreted in terms of an oxidase model similar to that put forward by Minnaert in 1961 (Minnaert, K. (1961) Biochim. Biophys. Acta 50, 23-34). 4. The Km for oxygen at infinite cytochrome c concentration is 0.95 muM and the intramolecular rate constant for the transfer of electrons from cytochrome c to cytochome aa3 is 400 s(-1). According to the model, this implies that the second order rate constant for the reaction between oxygen and the oxidase is 9.5 X 10(7)M(-1)-s(-1)."}
{"id": "PMID:186126", "title": "Purification and properties of soluble hydrogenase from Alcaligenes eutrophus H 16.", "content": "The soluble hydrogenase (hydrogen: NAD+ oxidoreductase, EC 1.12.1.2) from Alcaligenes eutrophus H 16 was purified 68-fold with a yield of 20% and a final specific activity (NAD reduction) of about 54 mumol H2 oxidized/min per mg protein. The enzyme was shown to be homogenous by polyacrylamide gel electrophoresis. Its molecular weight and isoelectric point were determined to be 205 000 and 4.85 respectively. The oxidized hydrogenase, as purified under aerobic conditions, was of high stability but not reactive. Reductive activation of the enzyme by H2, in the presence of catalytic amounts of NADH, or by reducing agents caused the hydrogenase to become unstable. The purified enzyme, in its active state, was able to reduce NAD, FMN, FAD, menaquinone, ubiquinone, cytochrome c, methylene blue, methyl viologen, benzyl viologen, phenazine methosulfate, janus green, 2,6-dichlorophenoloindophenol, ferricyanide and even oxygen. In addition to hydrogenase activitiy, the enzyme exhibited also diaphorase and NAD(P)H oxidase activity. The reversibility of hydrogenase function (i.e. H2 evolution from NADH, methyl viologen and benzyl viologen) was demonstrated. With respect to H2 as substrate, hydrogenase showed negative cooperativity; the Hill coefficient was n = 0.4. The apparent Km value for H2 was found to be 0.037 mM. The absorption spectrum of hydrogenase was typical for non-heme iron proteins, showing maxima (shoulders) at 380 and 420 nm. A flavin component could be extracted from native hydrogenase characterized by its absorption bands at 375 and 447 nm and a strong fluorescense at 526 nm.", "contents": "Purification and properties of soluble hydrogenase from Alcaligenes eutrophus H 16. The soluble hydrogenase (hydrogen: NAD+ oxidoreductase, EC 1.12.1.2) from Alcaligenes eutrophus H 16 was purified 68-fold with a yield of 20% and a final specific activity (NAD reduction) of about 54 mumol H2 oxidized/min per mg protein. The enzyme was shown to be homogenous by polyacrylamide gel electrophoresis. Its molecular weight and isoelectric point were determined to be 205 000 and 4.85 respectively. The oxidized hydrogenase, as purified under aerobic conditions, was of high stability but not reactive. Reductive activation of the enzyme by H2, in the presence of catalytic amounts of NADH, or by reducing agents caused the hydrogenase to become unstable. The purified enzyme, in its active state, was able to reduce NAD, FMN, FAD, menaquinone, ubiquinone, cytochrome c, methylene blue, methyl viologen, benzyl viologen, phenazine methosulfate, janus green, 2,6-dichlorophenoloindophenol, ferricyanide and even oxygen. In addition to hydrogenase activitiy, the enzyme exhibited also diaphorase and NAD(P)H oxidase activity. The reversibility of hydrogenase function (i.e. H2 evolution from NADH, methyl viologen and benzyl viologen) was demonstrated. With respect to H2 as substrate, hydrogenase showed negative cooperativity; the Hill coefficient was n = 0.4. The apparent Km value for H2 was found to be 0.037 mM. The absorption spectrum of hydrogenase was typical for non-heme iron proteins, showing maxima (shoulders) at 380 and 420 nm. A flavin component could be extracted from native hydrogenase characterized by its absorption bands at 375 and 447 nm and a strong fluorescense at 526 nm."}
{"id": "PMID:186127", "title": "Selective solubilization of the components of the mitochondrial inner membrane by lysolecithin.", "content": "1. Of various phospholipids tested, lysolecithin was the most efficient in the solubilization of the components of beef heart submitochondrial particles. Lysolecithin solubilized selectively nicotinamide nucleotide transhydrogenase, succinate dehydrogenase, NADH dehydrogenase and oligomycin-sensitive ATPase. Various cytochromes other than cytochrome c were only slightly solubilized. 2. The effect of various parameters, e.g. ionic strength, pH, time of centrifugation, and concentrations of lysolecithin and protein was investigated. Increasing times of centrifugation led to a partial sedimentation of NADH dehydrogenase, and a complete sedimentation of oligomycin-sensitive ATPase and cytochrome oxidase. 3. Further fractionation of the lysolecithin extract by centrifugation in the presence of low concentrations of cholate gave a complete separation of NADH dehydrogenase and transhydrogenase, indicating that these enzymes are not related functionally. 4. With the lysolecithin fractionation procedure a more than 10-fold purification of transhydrogenase was achieved. Polyacrylamide gel electrophoresis of the partially purified transhydrogenase in the presence of sodium dodecyl sulphate showed major increases in protein-stained bands corresponding to between 70 000 and 54 000 daltons. 5. A possible mechanism for the detergent action of lysolecithin involving a specific exchange of bound phospholipids for lysolecithin is discussed.", "contents": "Selective solubilization of the components of the mitochondrial inner membrane by lysolecithin. 1. Of various phospholipids tested, lysolecithin was the most efficient in the solubilization of the components of beef heart submitochondrial particles. Lysolecithin solubilized selectively nicotinamide nucleotide transhydrogenase, succinate dehydrogenase, NADH dehydrogenase and oligomycin-sensitive ATPase. Various cytochromes other than cytochrome c were only slightly solubilized. 2. The effect of various parameters, e.g. ionic strength, pH, time of centrifugation, and concentrations of lysolecithin and protein was investigated. Increasing times of centrifugation led to a partial sedimentation of NADH dehydrogenase, and a complete sedimentation of oligomycin-sensitive ATPase and cytochrome oxidase. 3. Further fractionation of the lysolecithin extract by centrifugation in the presence of low concentrations of cholate gave a complete separation of NADH dehydrogenase and transhydrogenase, indicating that these enzymes are not related functionally. 4. With the lysolecithin fractionation procedure a more than 10-fold purification of transhydrogenase was achieved. Polyacrylamide gel electrophoresis of the partially purified transhydrogenase in the presence of sodium dodecyl sulphate showed major increases in protein-stained bands corresponding to between 70 000 and 54 000 daltons. 5. A possible mechanism for the detergent action of lysolecithin involving a specific exchange of bound phospholipids for lysolecithin is discussed."}
{"id": "PMID:186128", "title": "Stimulation of Na+ transport across the toad urinary bladder by p-chloromercuribenzene sulfonate.", "content": "The sulfhydryl reagent p-chloromercuribenzene sulfonate increased the ISC across substrate-replete toad urinary bladder when applied to the mucosal (apical) surface. This increase was accounted for by an increased mucosal to serosal net flux of Na+. In the absence of substrate, the rise in ISC was accompanied by an irreversible increase in tissue conductance which was not apparent in the replete preparation. These findings suggest that p-chloromercuribenzene sulfonate may be useful in marking mucosal functions associated with the Na+ transport apparatus.", "contents": "Stimulation of Na+ transport across the toad urinary bladder by p-chloromercuribenzene sulfonate. The sulfhydryl reagent p-chloromercuribenzene sulfonate increased the ISC across substrate-replete toad urinary bladder when applied to the mucosal (apical) surface. This increase was accounted for by an increased mucosal to serosal net flux of Na+. In the absence of substrate, the rise in ISC was accompanied by an irreversible increase in tissue conductance which was not apparent in the replete preparation. These findings suggest that p-chloromercuribenzene sulfonate may be useful in marking mucosal functions associated with the Na+ transport apparatus."}
{"id": "PMID:186131", "title": "Nucleotide sequence study of mouse 5.8S ribosomal RNA.", "content": "The primary structure of 5.8S mouse ribosomal RNA has been studied and compared to the structures previously established for other animal species. The results obtained show that mouse 5.8S ribosomal RNA yields pancreatic oligonucleotides with the same nucleotide sequence as the homologous oligonucleotides from rat cells. Furthermore T1 oligonucleotides of 5.8S ribosomal RNA from rat, mouse and human cells behave identically on fingerprinting fractionation and have the same composition as judged by pancreatic digestion. These results strongly suggest that the primary structures of 5.8S ribosomal RNA from rat, mouse and human cells are identical. This identity of structure is also found when the presence of several modified bases (psi and methylated bases) is considered. The findings emphasize the remarkable evolutionary stability of ribosomal gene structure. Comparison of the terminal regional of 5.8S RNA with those of 18S RNA reveals differences which imply a more complex mechanism underlying the maturation of 45S precursor RNA than the finding of identical structure would have suggested.", "contents": "Nucleotide sequence study of mouse 5.8S ribosomal RNA. The primary structure of 5.8S mouse ribosomal RNA has been studied and compared to the structures previously established for other animal species. The results obtained show that mouse 5.8S ribosomal RNA yields pancreatic oligonucleotides with the same nucleotide sequence as the homologous oligonucleotides from rat cells. Furthermore T1 oligonucleotides of 5.8S ribosomal RNA from rat, mouse and human cells behave identically on fingerprinting fractionation and have the same composition as judged by pancreatic digestion. These results strongly suggest that the primary structures of 5.8S ribosomal RNA from rat, mouse and human cells are identical. This identity of structure is also found when the presence of several modified bases (psi and methylated bases) is considered. The findings emphasize the remarkable evolutionary stability of ribosomal gene structure. Comparison of the terminal regional of 5.8S RNA with those of 18S RNA reveals differences which imply a more complex mechanism underlying the maturation of 45S precursor RNA than the finding of identical structure would have suggested."}
{"id": "PMID:186133", "title": "Comparison of zymogram of three lymphoblastoid cell lines with a new microtechnique.", "content": "The enzymatic activities of three lymphoblastoid cell lines were subjected to a comparative analysis of 22 enzymatic activities with a new microtechnique \"Apizym\". This method is easy, requires only a small number of cells and allows simultaneous testing of many enzymatic activities from the same sample. The three cell lines can be easily distinguished despite their close origin: NAB, derived from a malignant retroperitoneal mass in an American patient, is the cell line with the greatest total activity and HRlK (a clone of P3J, derived from an African lymphoma) with the lowest and RAJI (a non-virus producing line derived from an African lymphoma) being the intermediate. The more striking differences concern the activity of phosphatases (NAB greater than RAJI greater than or equal to HRlK), esterases-lipases (NAB greater than or equal to RAJI greater than HRlK), beta glucosaminidase, beta glucuronidase beta glucosidase (NAB greater than or equal to RAJI greater than HRlK). On the other hand, alpha mannosidase and alpha fucosidase are more active in RAJI (RAJI greater than NAB greater than or equal to HRlK).", "contents": "Comparison of zymogram of three lymphoblastoid cell lines with a new microtechnique. The enzymatic activities of three lymphoblastoid cell lines were subjected to a comparative analysis of 22 enzymatic activities with a new microtechnique \"Apizym\". This method is easy, requires only a small number of cells and allows simultaneous testing of many enzymatic activities from the same sample. The three cell lines can be easily distinguished despite their close origin: NAB, derived from a malignant retroperitoneal mass in an American patient, is the cell line with the greatest total activity and HRlK (a clone of P3J, derived from an African lymphoma) with the lowest and RAJI (a non-virus producing line derived from an African lymphoma) being the intermediate. The more striking differences concern the activity of phosphatases (NAB greater than RAJI greater than or equal to HRlK), esterases-lipases (NAB greater than or equal to RAJI greater than HRlK), beta glucosaminidase, beta glucuronidase beta glucosidase (NAB greater than or equal to RAJI greater than HRlK). On the other hand, alpha mannosidase and alpha fucosidase are more active in RAJI (RAJI greater than NAB greater than or equal to HRlK)."}
{"id": "PMID:186134", "title": "An appraisal of the interrelationships between prostaglandins and cyclic nucleotides in inflammation.", "content": "The evidence supporting the role of prostaglandins and cyclic nucleotides \"in vitro\" has been reviewed. The pro-inflammatory role of prostaglandins of the E series (PGE) is typified by its ability to induce increased vascular permeability. Prostaglandins of the F series (PGF) may be anti-inflammatory via their inhibitory effect on increased vascular permeability. However, a paradox exists which suggests that PGE may also be anti-inflammatory via its stimulatory effect on cyclic AMP synthesis as shown \"in vitro\" (e.g. decreased leucocyte lysosomal enzyme secretion; decreased lymphocyte cytotoxicity and mitosis; decreased release of mediators from sensitized tissues during anaphylaxis). Conversely PGF is capable of stimulating cyclic GMP which augments the processes listed above, and may therefore be termed pro-inflammatory. An attempt has been made to correlate these findings with \"in vivo\" studies which support the anti-inflammatory role of cyclic GMP. However, the significance of PGE and PGF in the inflammatory response \"in vivo\" appears to be more complex. It is suggested that greater emphasis should be placed on the \"in vivo\" study of beta-adrenergic and cholinergic mediators, substances which induce the anti- and pro-inflammatory effects of cyclic AMP and cyclic GMP \"in vitro\", respectively.", "contents": "An appraisal of the interrelationships between prostaglandins and cyclic nucleotides in inflammation. The evidence supporting the role of prostaglandins and cyclic nucleotides \"in vitro\" has been reviewed. The pro-inflammatory role of prostaglandins of the E series (PGE) is typified by its ability to induce increased vascular permeability. Prostaglandins of the F series (PGF) may be anti-inflammatory via their inhibitory effect on increased vascular permeability. However, a paradox exists which suggests that PGE may also be anti-inflammatory via its stimulatory effect on cyclic AMP synthesis as shown \"in vitro\" (e.g. decreased leucocyte lysosomal enzyme secretion; decreased lymphocyte cytotoxicity and mitosis; decreased release of mediators from sensitized tissues during anaphylaxis). Conversely PGF is capable of stimulating cyclic GMP which augments the processes listed above, and may therefore be termed pro-inflammatory. An attempt has been made to correlate these findings with \"in vivo\" studies which support the anti-inflammatory role of cyclic GMP. However, the significance of PGE and PGF in the inflammatory response \"in vivo\" appears to be more complex. It is suggested that greater emphasis should be placed on the \"in vivo\" study of beta-adrenergic and cholinergic mediators, substances which induce the anti- and pro-inflammatory effects of cyclic AMP and cyclic GMP \"in vitro\", respectively."}
{"id": "PMID:186137", "title": "[Adrenal glucocorticoid function and cytoplasmic dehydrogenase activity in the presnece of mechanical and toxic liver damage].", "content": "Against the background of low steroid metabolism in the liver there was noted some decrease in the rate of corticosterone synthesis by the adrenal gland sections, and also, a decrease in the dehydrogenase activity in the cytoplasm of adrenal cells in male rats 48 hours after partial hepatectomy, as compared to the sham-operated animals. These changes resulted from suppression of the central mechanisms of stress realization due to the lowered steroid metabolism. Intraperitoneal administration of carbon tetrachloride (0.1 ml per 100 g of body weight) at the same periods led to a significant intensification of the steroidogenesis in the adrenal tissue and to the activation of NAD-dependent dehydrogenases in the cytoplasm. The role of toxic injury of the glands in the changes of the functional state of the adrenal cortex cells is discussed.", "contents": "[Adrenal glucocorticoid function and cytoplasmic dehydrogenase activity in the presnece of mechanical and toxic liver damage]. Against the background of low steroid metabolism in the liver there was noted some decrease in the rate of corticosterone synthesis by the adrenal gland sections, and also, a decrease in the dehydrogenase activity in the cytoplasm of adrenal cells in male rats 48 hours after partial hepatectomy, as compared to the sham-operated animals. These changes resulted from suppression of the central mechanisms of stress realization due to the lowered steroid metabolism. Intraperitoneal administration of carbon tetrachloride (0.1 ml per 100 g of body weight) at the same periods led to a significant intensification of the steroidogenesis in the adrenal tissue and to the activation of NAD-dependent dehydrogenases in the cytoplasm. The role of toxic injury of the glands in the changes of the functional state of the adrenal cortex cells is discussed."}
{"id": "PMID:186138", "title": "[Effect of imidazole compounds on the activity of adenosine-3', 5'-monophosphoric acid phosphodiesterase].", "content": "The effect of 24 imidazol derivatives on the activity of phosphodiesterase (3', 5'-AMP-phosphohydrolase; KF3.1.4.1) was studied in the experiments with the homogenates of the rat brain and of the Rana temporaria skeletal muscles. Imidazol derivatives could produce both the activating and inhibitory influence on the enzyme. Imidazol and seven of its alkyl-substituted derivatives activated the phosphodiesterase. TTFB (tetrachloro-2-trifluoromethylbenzimidazol) produced the greatest inhibitory effect among the inhibitors on the phosphodiesterase activity.", "contents": "[Effect of imidazole compounds on the activity of adenosine-3', 5'-monophosphoric acid phosphodiesterase]. The effect of 24 imidazol derivatives on the activity of phosphodiesterase (3', 5'-AMP-phosphohydrolase; KF3.1.4.1) was studied in the experiments with the homogenates of the rat brain and of the Rana temporaria skeletal muscles. Imidazol derivatives could produce both the activating and inhibitory influence on the enzyme. Imidazol and seven of its alkyl-substituted derivatives activated the phosphodiesterase. TTFB (tetrachloro-2-trifluoromethylbenzimidazol) produced the greatest inhibitory effect among the inhibitors on the phosphodiesterase activity."}
{"id": "PMID:186139", "title": "[Possible participation of cyclic AMP in regulating acid hydrolase activity in muscle tissue in avitaminosis E and denervation].", "content": "In the muscles of denervated and vitamin E-deficient rabbits the level of 3', 5'-cyclic AMP proved to decrease with a simultaneous increase in the activity of cAMP phosphodiesterase. In vivo experiments showed that at the concentration of 10(-4) cAMP was capable of retarding the release of acid phosphatase from the lysosome-rich fraction obtained from the muscles of E-deficient rabbits. Thus, in muscular dystrophy elevation of acid hydrolase activity in the skeletal muscle was due to leakage of the enzymes from the lysosomes as a result of decreased lysosome membrane stability because of decreased cAMP level.", "contents": "[Possible participation of cyclic AMP in regulating acid hydrolase activity in muscle tissue in avitaminosis E and denervation]. In the muscles of denervated and vitamin E-deficient rabbits the level of 3', 5'-cyclic AMP proved to decrease with a simultaneous increase in the activity of cAMP phosphodiesterase. In vivo experiments showed that at the concentration of 10(-4) cAMP was capable of retarding the release of acid phosphatase from the lysosome-rich fraction obtained from the muscles of E-deficient rabbits. Thus, in muscular dystrophy elevation of acid hydrolase activity in the skeletal muscle was due to leakage of the enzymes from the lysosomes as a result of decreased lysosome membrane stability because of decreased cAMP level."}
{"id": "PMID:186141", "title": "Membrane changes in virus transformed cells.", "content": "Various aspects of membrane changes in cells transformed by oncogenic viruses are briefly described and discussed. Emphasis is made on changes recently observed in the hydrophobic portion of plasma membrane with the freeze-etching technique. The hypothesis is put forward that other changes seen at the surface of transformed cells are caused by a primary event occuring in proteins of the hydrophobic area.", "contents": "Membrane changes in virus transformed cells. Various aspects of membrane changes in cells transformed by oncogenic viruses are briefly described and discussed. Emphasis is made on changes recently observed in the hydrophobic portion of plasma membrane with the freeze-etching technique. The hypothesis is put forward that other changes seen at the surface of transformed cells are caused by a primary event occuring in proteins of the hydrophobic area."}
{"id": "PMID:186142", "title": "[Transmission and expression of malignancy in somatic hybrid cell lines (hamster/hamster, mouse/mouse, hamster/mouse)].", "content": "Various characteristics of transformation were studied in subclones isolated from a hybrid cell line obtained by fusion of two Chinese hamster sub-lines having the same origin but presenting different properties, particularly in respect to heterotransplantability. Different subclones were obtained by cloning on semisoft agar. Transplantability, plating efficiency, agglutinability by concanavalin A and actinomycin D resistance were studied in parallel with the evolution of the karyotype to try to find a correlation between these various parameters. A relationship seems to exist between a chromosome marker arising in the hybrid and the percentage of tumours. The second part of this work dealth with the study of intra and interspecies hybrids, one of the parents of which was a normal, fibroblastic cell and the other of which contained the polyoma virus genome. In the hybrid cell this viral genome was expressed at several levels. Firstly, in the formation of specific polyoma virus-induced antigens and secondaryly, in surface properties normally considered related to the expression of tumorigenicity. Nevertheless, tumour development was repressed. Though the presence of characteristic antigens seemed necessary for the expression of malignant transformation, presence alone was not sufficient to induce malignant transformation of the cell. The study of inter-species mouse/hamster hybrids showed that this situation is not general. For this we examined the properties of hybrid cells between, on the one hand, a mouse tumorigenic cell bearing polyoma virus genetic information and, on the other, non-tumorigenic mouse or hamster cell. In this case the complete hamster genome could bot repress malignancy whereas a few mouse chromosomes sufficed to code for the expression of virus-induced tumour antigens and various malignant properties. It may be hoped that these hybrids could be used to pin-point the chromosome localization of the genetic factors of malignancy and could be used in immunoprotection studies or immunotherapy research.", "contents": "[Transmission and expression of malignancy in somatic hybrid cell lines (hamster/hamster, mouse/mouse, hamster/mouse)]. Various characteristics of transformation were studied in subclones isolated from a hybrid cell line obtained by fusion of two Chinese hamster sub-lines having the same origin but presenting different properties, particularly in respect to heterotransplantability. Different subclones were obtained by cloning on semisoft agar. Transplantability, plating efficiency, agglutinability by concanavalin A and actinomycin D resistance were studied in parallel with the evolution of the karyotype to try to find a correlation between these various parameters. A relationship seems to exist between a chromosome marker arising in the hybrid and the percentage of tumours. The second part of this work dealth with the study of intra and interspecies hybrids, one of the parents of which was a normal, fibroblastic cell and the other of which contained the polyoma virus genome. In the hybrid cell this viral genome was expressed at several levels. Firstly, in the formation of specific polyoma virus-induced antigens and secondaryly, in surface properties normally considered related to the expression of tumorigenicity. Nevertheless, tumour development was repressed. Though the presence of characteristic antigens seemed necessary for the expression of malignant transformation, presence alone was not sufficient to induce malignant transformation of the cell. The study of inter-species mouse/hamster hybrids showed that this situation is not general. For this we examined the properties of hybrid cells between, on the one hand, a mouse tumorigenic cell bearing polyoma virus genetic information and, on the other, non-tumorigenic mouse or hamster cell. In this case the complete hamster genome could bot repress malignancy whereas a few mouse chromosomes sufficed to code for the expression of virus-induced tumour antigens and various malignant properties. It may be hoped that these hybrids could be used to pin-point the chromosome localization of the genetic factors of malignancy and could be used in immunoprotection studies or immunotherapy research."}
{"id": "PMID:186151", "title": "Degeneration in central and peripheral nervous systems produced by pure n-hexane: an experimental study.", "content": "Rats intoxicated with pure n-hexane, either by repetitive subcutaneous injection or by continuous inhalation, developed clinical and/or pathological evidence of peripheral neuropathy. Animals intoxicated by inhalation (400-600 ppm) developed clinical signs after forty-five days and displayed giant axonal swellings and fibre degeneration both in the central and peripheral nervous systems. The changes were most strking in tibial nerves supplying calf muscles and in selected areas of the cerebellum, medulla and spinal cord. In contrast to the usual picture associated with dying-back disease, the distal regions of proximal nerve fibres supplying calf muscles degenerated before equivalent regions of longer fibres supplying the hindfeet. The relevance of the central nervous changes to individuals recovering from toxic neuropathies and the need for a reduction of the present Threshold Limit Value (500 ppm) for human exposure are discussed.", "contents": "Degeneration in central and peripheral nervous systems produced by pure n-hexane: an experimental study. Rats intoxicated with pure n-hexane, either by repetitive subcutaneous injection or by continuous inhalation, developed clinical and/or pathological evidence of peripheral neuropathy. Animals intoxicated by inhalation (400-600 ppm) developed clinical signs after forty-five days and displayed giant axonal swellings and fibre degeneration both in the central and peripheral nervous systems. The changes were most strking in tibial nerves supplying calf muscles and in selected areas of the cerebellum, medulla and spinal cord. In contrast to the usual picture associated with dying-back disease, the distal regions of proximal nerve fibres supplying calf muscles degenerated before equivalent regions of longer fibres supplying the hindfeet. The relevance of the central nervous changes to individuals recovering from toxic neuropathies and the need for a reduction of the present Threshold Limit Value (500 ppm) for human exposure are discussed."}
{"id": "PMID:186152", "title": "Inputs to trigeminal brain stem neurones from facial, oral, tooth pulp and pharyngolaryngeal tissues: II. Role of trigeminal nucleus caudalis in modulating responses to innocuous and noxious stimuli.", "content": "Trigeminal (V) tractotomy and cold block of synaptic transmission in V nucleus caudalis were used to show that caudalis modulates the responses to innocuous and noxious stimuli of single V main sensory-oralis neurones recorded in anaesthetized or decerebrate cats. Cold block caused a reversible depression of mechanosensitivity of 91 of 105 V-thalamic relay and non-relay cells tested; V tractotomy also decreased sensitivity. The possibliity that the effects observed with cold block of caudalis were caused by direct spread of cooling to the main sensory-oralis region, and not by depression of a tonic, net facilitatory influence of caudalis on main sensory-oralis cells, was ruled out by several controls. With cold block of caudalis there also occurred a reversible shrinkage in mechanoreceptive field size and reversible reduction in sensitivity of rapidly adapting and slowly adapting mechanoreceptive neurones. Occasionally no change or an increase in sensitivity occurred, the latter suggesting the liklihood of an inhibitory influence from caudalis as well as the facilitatory influence. The effects of interactions of innocuous and noxious V stimuli were likewise subject to ascending influences from caudalis. Cold block also reversibly depressed responses to tooth pulp and V cutaneous noxious stimuli, although pulp-evoked responses were depressed less than mechanical or infraorbital nerve-elicited responses. Our results indicate that caudalis, as well as acting as a relay site to thalamus, also exerts a predominantly facilitatory influence on the relay to the thalamus and local reflex centres of mechanoreceptive and nociceptive information through the V main sensory-oralis region. The findings also might in part explain the analgesia, partial loss of tactile sensibility, and relief from V neuralgia reported after V tractotomy.", "contents": "Inputs to trigeminal brain stem neurones from facial, oral, tooth pulp and pharyngolaryngeal tissues: II. Role of trigeminal nucleus caudalis in modulating responses to innocuous and noxious stimuli. Trigeminal (V) tractotomy and cold block of synaptic transmission in V nucleus caudalis were used to show that caudalis modulates the responses to innocuous and noxious stimuli of single V main sensory-oralis neurones recorded in anaesthetized or decerebrate cats. Cold block caused a reversible depression of mechanosensitivity of 91 of 105 V-thalamic relay and non-relay cells tested; V tractotomy also decreased sensitivity. The possibliity that the effects observed with cold block of caudalis were caused by direct spread of cooling to the main sensory-oralis region, and not by depression of a tonic, net facilitatory influence of caudalis on main sensory-oralis cells, was ruled out by several controls. With cold block of caudalis there also occurred a reversible shrinkage in mechanoreceptive field size and reversible reduction in sensitivity of rapidly adapting and slowly adapting mechanoreceptive neurones. Occasionally no change or an increase in sensitivity occurred, the latter suggesting the liklihood of an inhibitory influence from caudalis as well as the facilitatory influence. The effects of interactions of innocuous and noxious V stimuli were likewise subject to ascending influences from caudalis. Cold block also reversibly depressed responses to tooth pulp and V cutaneous noxious stimuli, although pulp-evoked responses were depressed less than mechanical or infraorbital nerve-elicited responses. Our results indicate that caudalis, as well as acting as a relay site to thalamus, also exerts a predominantly facilitatory influence on the relay to the thalamus and local reflex centres of mechanoreceptive and nociceptive information through the V main sensory-oralis region. The findings also might in part explain the analgesia, partial loss of tactile sensibility, and relief from V neuralgia reported after V tractotomy."}
{"id": "PMID:186153", "title": "Response of toad brain respiratory chain enzymes to ouabain, elevated potassium, and electrical stimulus.", "content": "Spectrophotometric and fluorometric techniques were used to monitor the proportion of reduced to oxidized cytochrome (cyt) and levels of reduced pyridine nucleotide in preparations of whole toad brain in vitro. In resting, well-oxygenated brain, levels of reduction for cyt a3 ranged between 5% and 23%; for cyt a, 17-23%; for cyt c, 18-32%, and for cyt b, 25-42%. These levels of reduction cannot be due to functional hypoxia since hemoglobin in resting brains is 100% oxygenated. In brains treated with 10(-4) M ouabain, stimulant of brain respiration, the cytochromes first become more oxidized, then more reduced; ultimately there is a tendency to return to the initial levels of reduction. In brains bathed with solutions containing 30 mM potassium, also a stimulant of brain respiration, the response is an immediate pulse of reduction in all cytochromes, followed by a tendency to return to the initial levels. Short trains of pulses of electrical field stimulation result in a biphasic change in the level of reduction of cyt a3, an initial slight reduction being followed by a transient of increased oxidation. This response can be abolished by low-sodium bathing solution but not by ouabain. Cytochromes a, b and c show a simple oxidative response to electrical stimulation; the kinetics of this oxidative response are similar to those of the oxidative transient of the cyt a3 response. Pyridine nucleotides, as measured by their fluorescence, respond to electrical stimulation with a transient oxidation which exhibits slower kinetics than the response of the cytochromes. The high resting levels of reduction of cyt a and cyt a3, the reductive response to ouabain and potassium, and the oxidative response of all cytochromes to electrical stimulation suggest a tighter coupling between oxygen utilization and neuronal function than would be expected if mitochondrial redox states simply reflected changes in phosphate acceptor potential resulting from activity of Na+-K+ ATPase.", "contents": "Response of toad brain respiratory chain enzymes to ouabain, elevated potassium, and electrical stimulus. Spectrophotometric and fluorometric techniques were used to monitor the proportion of reduced to oxidized cytochrome (cyt) and levels of reduced pyridine nucleotide in preparations of whole toad brain in vitro. In resting, well-oxygenated brain, levels of reduction for cyt a3 ranged between 5% and 23%; for cyt a, 17-23%; for cyt c, 18-32%, and for cyt b, 25-42%. These levels of reduction cannot be due to functional hypoxia since hemoglobin in resting brains is 100% oxygenated. In brains treated with 10(-4) M ouabain, stimulant of brain respiration, the cytochromes first become more oxidized, then more reduced; ultimately there is a tendency to return to the initial levels of reduction. In brains bathed with solutions containing 30 mM potassium, also a stimulant of brain respiration, the response is an immediate pulse of reduction in all cytochromes, followed by a tendency to return to the initial levels. Short trains of pulses of electrical field stimulation result in a biphasic change in the level of reduction of cyt a3, an initial slight reduction being followed by a transient of increased oxidation. This response can be abolished by low-sodium bathing solution but not by ouabain. Cytochromes a, b and c show a simple oxidative response to electrical stimulation; the kinetics of this oxidative response are similar to those of the oxidative transient of the cyt a3 response. Pyridine nucleotides, as measured by their fluorescence, respond to electrical stimulation with a transient oxidation which exhibits slower kinetics than the response of the cytochromes. The high resting levels of reduction of cyt a and cyt a3, the reductive response to ouabain and potassium, and the oxidative response of all cytochromes to electrical stimulation suggest a tighter coupling between oxygen utilization and neuronal function than would be expected if mitochondrial redox states simply reflected changes in phosphate acceptor potential resulting from activity of Na+-K+ ATPase."}
{"id": "PMID:186154", "title": "The thiol-oxidizing agent diamide increases transmitter release by decreasing calcium requirements for neuromuscular transmission in the frog.", "content": "Diamide, which in concentrations of 10(-5) M and higher oxidizes glutathione intracellularly, produces a dose-related increase in the frequency of miniature end-plate potentials (MEPPs). With high enough doses, quantal release is blocked, apparently through exhaustion. The early phase of MEPP frequency increase is accompanied by an increase in EPP amplitude that may reach more than 10-fold and is therefore not produced by depolarization of axon terminals. Subsequently, EPP amplitude is reduced and falls to zero, associated with failure of invasion of the nerve action into the terminals while the MEPP frequency remains elevated. Both facilitation and PTP follow the time course of change in EPP amplitude. The increase in MEPP frequency with diamide does not require external Ca2+ but raising external Ca2+ increases the MEPP rate in the presence of diamide. External Ca2+ is necessary for EPP appearance and also potentiates the diamide effects. Conversely diamide reduces the requirements for Ca2+ in releasing ACh. Diamide substitutes for external Ca2+ in K+ evoked MEPP release and in the absence of external Ca2+, diamide-evoked MEPP release is increased by raising external Mg2+ levels. The action of diamide may be dependent on the actual release of Ca2+ from intracellular stores or it may work through mimicking some of the actions of Ca2+. The action of diamide bears close resemblance to the effects of prolonged stimulation of the motor axon at 10 Hz.", "contents": "The thiol-oxidizing agent diamide increases transmitter release by decreasing calcium requirements for neuromuscular transmission in the frog. Diamide, which in concentrations of 10(-5) M and higher oxidizes glutathione intracellularly, produces a dose-related increase in the frequency of miniature end-plate potentials (MEPPs). With high enough doses, quantal release is blocked, apparently through exhaustion. The early phase of MEPP frequency increase is accompanied by an increase in EPP amplitude that may reach more than 10-fold and is therefore not produced by depolarization of axon terminals. Subsequently, EPP amplitude is reduced and falls to zero, associated with failure of invasion of the nerve action into the terminals while the MEPP frequency remains elevated. Both facilitation and PTP follow the time course of change in EPP amplitude. The increase in MEPP frequency with diamide does not require external Ca2+ but raising external Ca2+ increases the MEPP rate in the presence of diamide. External Ca2+ is necessary for EPP appearance and also potentiates the diamide effects. Conversely diamide reduces the requirements for Ca2+ in releasing ACh. Diamide substitutes for external Ca2+ in K+ evoked MEPP release and in the absence of external Ca2+, diamide-evoked MEPP release is increased by raising external Mg2+ levels. The action of diamide may be dependent on the actual release of Ca2+ from intracellular stores or it may work through mimicking some of the actions of Ca2+. The action of diamide bears close resemblance to the effects of prolonged stimulation of the motor axon at 10 Hz."}
{"id": "PMID:186155", "title": "Free amino acids and related substances in human glial tumours and in fetal brain: comparison with normal adult brain.", "content": "An ion exchange automatic chromatographic analysis of the free amino acid concentrations of 18 human glial tumours and of 4 human fetal brains was carried out and the concentrations were compared to those of 13 biopsy specimens of normal adult brain. In addition, the concentrations of the amino acids of the glial tumours were compared to those of 7 intracerebral metastases of various origin. The chromatograms of several tumour specimens showed an unidentified peak overlapping proline. As far as the amino acid concentrations are concerned they varied depending upon the origin of the sample. The concentrations of most amino acids were higher in fetal brain than in adult brain with the exception of aspartic acid, glutamic acid, glutamine, cystathionine and GABA. Two peptides: glutathione and homocarnosine were absent in fetal brain and were present in adult brain. In glial tumours, homocarnosine and some amino acids, namely aspartic acid, glutamic acid and GABA, showed lower concentrations than in normal brain. Some amino acids were in the same concentration as in normal brain: taurine, phosphoethanolamine, glutamine and cystathionine. Most of the others were in higher concentrations than in normal brain, mainly proline. The results suggest that the concentrations of 5 compounds: taurine, proline, cystathionine, GABA and homocarnosine, taken as a whole, provide information on the origin of the sample.", "contents": "Free amino acids and related substances in human glial tumours and in fetal brain: comparison with normal adult brain. An ion exchange automatic chromatographic analysis of the free amino acid concentrations of 18 human glial tumours and of 4 human fetal brains was carried out and the concentrations were compared to those of 13 biopsy specimens of normal adult brain. In addition, the concentrations of the amino acids of the glial tumours were compared to those of 7 intracerebral metastases of various origin. The chromatograms of several tumour specimens showed an unidentified peak overlapping proline. As far as the amino acid concentrations are concerned they varied depending upon the origin of the sample. The concentrations of most amino acids were higher in fetal brain than in adult brain with the exception of aspartic acid, glutamic acid, glutamine, cystathionine and GABA. Two peptides: glutathione and homocarnosine were absent in fetal brain and were present in adult brain. In glial tumours, homocarnosine and some amino acids, namely aspartic acid, glutamic acid and GABA, showed lower concentrations than in normal brain. Some amino acids were in the same concentration as in normal brain: taurine, phosphoethanolamine, glutamine and cystathionine. Most of the others were in higher concentrations than in normal brain, mainly proline. The results suggest that the concentrations of 5 compounds: taurine, proline, cystathionine, GABA and homocarnosine, taken as a whole, provide information on the origin of the sample."}
{"id": "PMID:186156", "title": "Synaptic transmission between rat spinal cord explants and dissociated superior cervical ganglion neurons in tissue culture.", "content": "Physiological properties of the synapses formed between explants of spinal cord and dissociated autonomic ganglion neurons in tissue culture were studied using intracellular and extracellular stimulation and recording techniques (as well as iontophoresis) with a culture perfusion system allowing continuous microscopic observation during repeated changes of the bathing medium. The principal neurons of the superior cervical ganglion (SCGN) were dissociated from perinatal rats and the spinal cord explants were obtained from 15-day rat fetuses; these were allowed to mature for 3-10 weeks in co-culture. Recordings from over 1000 SCGN established that: (a) spontaneous small depolarizations and action potentials occurred in 20% of the SCGN studied, (b) the EPSPs observed in SCGN after spinal cord stimulation were sensitive to decreased Ca2+ and increased Mg2+, as well as to D-tubocurare, hexamethonium and mecamylamine, but not to atropine (at 10(-6) M concentration) or to the alpha-adrenergic blocking agents phentolamine or phenoxybenzamine; no potentiation of the EPSPs was seen with neostigmate or eserine, (c) acetylcholine directly applied to the SCGN was seen to mimic the responses seen after spinal cord stimulation; tetrodotoxin blocked both direct and iontophoretically fired action potentials, with only a suprathreshold acetylcholine potential remaining. These synapses were not sensitive to alpha-bungarotoxin. It is concluded that the synapses formed by spinal cord neurites on principal SCGN in tissue culture are nicotinic cholinergic, and that the evoked EPSPs recorded in this study are thus similar to the orthodromic fast EPSPs observed in vivo. No slow synaptic responses were observed and no demonstrable effects were noted that could be attributed to adrenergic transmission.", "contents": "Synaptic transmission between rat spinal cord explants and dissociated superior cervical ganglion neurons in tissue culture. Physiological properties of the synapses formed between explants of spinal cord and dissociated autonomic ganglion neurons in tissue culture were studied using intracellular and extracellular stimulation and recording techniques (as well as iontophoresis) with a culture perfusion system allowing continuous microscopic observation during repeated changes of the bathing medium. The principal neurons of the superior cervical ganglion (SCGN) were dissociated from perinatal rats and the spinal cord explants were obtained from 15-day rat fetuses; these were allowed to mature for 3-10 weeks in co-culture. Recordings from over 1000 SCGN established that: (a) spontaneous small depolarizations and action potentials occurred in 20% of the SCGN studied, (b) the EPSPs observed in SCGN after spinal cord stimulation were sensitive to decreased Ca2+ and increased Mg2+, as well as to D-tubocurare, hexamethonium and mecamylamine, but not to atropine (at 10(-6) M concentration) or to the alpha-adrenergic blocking agents phentolamine or phenoxybenzamine; no potentiation of the EPSPs was seen with neostigmate or eserine, (c) acetylcholine directly applied to the SCGN was seen to mimic the responses seen after spinal cord stimulation; tetrodotoxin blocked both direct and iontophoretically fired action potentials, with only a suprathreshold acetylcholine potential remaining. These synapses were not sensitive to alpha-bungarotoxin. It is concluded that the synapses formed by spinal cord neurites on principal SCGN in tissue culture are nicotinic cholinergic, and that the evoked EPSPs recorded in this study are thus similar to the orthodromic fast EPSPs observed in vivo. No slow synaptic responses were observed and no demonstrable effects were noted that could be attributed to adrenergic transmission."}
{"id": "PMID:186157", "title": "Synaptic transmission between rat superior cervical ganglion neurons in dissociated cell cultures.", "content": "The principal neurons of the rat superior cervical ganglion (SCGN) when established as dissociated cells in tissue culture form synapses among themselves. In the present study we have examined this synaptic interaction when these neurons are co-cultured with several other types of tissues. Dissociated SCGN were prepared from perinatal rats and studied, after 3-4 weeks maturation, with intracellular recording techniques. Synaptic interactions between sympathetic neurons were demonstrated when these cells were: (a) grown with explants from newborn rat thoracic spinal cord, (b) when the SCGN had survived for several weeks subsequent to removal of the spinal cord explants, and (c) when the SCGN were grown in the presence of an adrenergic target (interscapular brown fat cells). Unidirectional, reciprocal, recurrent and complex chemical synaptic networks, consisting of convergence and divergence, characterized connections between SCGN. All synaptic responses were cholinergic since they were reversibly blocked by hexamethonium or mecamylamine but were not sensitive to 10(-5) M phenoxybenzamine. Removal of the spinal cord explants did not significantly alter the proportion of chemical synaptic interactions between SCGN (more than 25%) from matched cultures. Anatomical observations established that in cultures with brown fat, innervating neurites appeared on the fat cells; these neurites frequently expanded to form varicosities that resembled the adrenergic terminals normally seen on brown fat in the animal. Synaptic profiles also occurred on the neurons in these cultures and some of these were shown to be cholinergic. The proportion of neuronal interactions in the combined SCGN + fat cultures was low, however, suggesting that co-culture with target tissue might influence the frequency of interconnections developed between SCGN in culture. Other factors, such as the presence of non-neuronal cells, degree of dissociation, cellular density, culture age and the survival of certain types of SCGN in culture are discussed as variables related to the formation of synapses between SCGN. Non-rectified electrical coupling between SCGN was also observed in 17 out of 679 pairs (2.5%) of neurons. Attenuation factor for electrically coupled action potentials ranged between 1 and 43.5.", "contents": "Synaptic transmission between rat superior cervical ganglion neurons in dissociated cell cultures. The principal neurons of the rat superior cervical ganglion (SCGN) when established as dissociated cells in tissue culture form synapses among themselves. In the present study we have examined this synaptic interaction when these neurons are co-cultured with several other types of tissues. Dissociated SCGN were prepared from perinatal rats and studied, after 3-4 weeks maturation, with intracellular recording techniques. Synaptic interactions between sympathetic neurons were demonstrated when these cells were: (a) grown with explants from newborn rat thoracic spinal cord, (b) when the SCGN had survived for several weeks subsequent to removal of the spinal cord explants, and (c) when the SCGN were grown in the presence of an adrenergic target (interscapular brown fat cells). Unidirectional, reciprocal, recurrent and complex chemical synaptic networks, consisting of convergence and divergence, characterized connections between SCGN. All synaptic responses were cholinergic since they were reversibly blocked by hexamethonium or mecamylamine but were not sensitive to 10(-5) M phenoxybenzamine. Removal of the spinal cord explants did not significantly alter the proportion of chemical synaptic interactions between SCGN (more than 25%) from matched cultures. Anatomical observations established that in cultures with brown fat, innervating neurites appeared on the fat cells; these neurites frequently expanded to form varicosities that resembled the adrenergic terminals normally seen on brown fat in the animal. Synaptic profiles also occurred on the neurons in these cultures and some of these were shown to be cholinergic. The proportion of neuronal interactions in the combined SCGN + fat cultures was low, however, suggesting that co-culture with target tissue might influence the frequency of interconnections developed between SCGN in culture. Other factors, such as the presence of non-neuronal cells, degree of dissociation, cellular density, culture age and the survival of certain types of SCGN in culture are discussed as variables related to the formation of synapses between SCGN. Non-rectified electrical coupling between SCGN was also observed in 17 out of 679 pairs (2.5%) of neurons. Attenuation factor for electrically coupled action potentials ranged between 1 and 43.5."}
{"id": "PMID:186160", "title": "Facilitation and depression of synaptic transmission in amphibian sympathetic ganglia.", "content": "There have been few reports concerning facilitation and depression in sympathetic ganglia9,17,40. In the present investigation, pairs of excitatory postsynaptic potentials (EPSPs) were recorded intracellularly from bullfrog paravertebral sympathetic ganglia for an analysis of the site and mechanism responsible for the phenomena of facilitation and depression of ganglionic transmission. The ratio of the amplitude of the second of a depression of ganglionic transmission. The ratio of the amplitude of the second of a pair of EPSPs divided by the first was compared to the time interval between each pair of EPSPs divided by the first was compared to the time interval between each pulse. These ratios demonstrated two phases: an earlier phase of facilitation (20-500 msec pulse intervals) and a later phase of depression (500 msec-10 sec). Additional parameters-rate of rise of synaptic potentials (dV/dt), synaptic currents (EPSCs), and synaptic conductances (Gtr)-were determined and all confirmed the results obtained with EPSPs. Furthermore, the degree of facilitation or depression could be modulated by altering the extracellular concentration of calcium. On the other hand, comparison of the amplitude of pairs of presynaptic terminal spikes did not show any variability over similar stimulus intervals, nor were the amplitudes of miniature EPSPs significantly different before or after an evoked EPSP. Therefore, the processes of facilitation and depression of ganglionic transmission occur as a result of normal nerve terminal activity. The processes are occurring simultaneously, such that one or the other may predominate depending upon the interval between pulses, as well as the relative concentration of extracellular calcium.", "contents": "Facilitation and depression of synaptic transmission in amphibian sympathetic ganglia. There have been few reports concerning facilitation and depression in sympathetic ganglia9,17,40. In the present investigation, pairs of excitatory postsynaptic potentials (EPSPs) were recorded intracellularly from bullfrog paravertebral sympathetic ganglia for an analysis of the site and mechanism responsible for the phenomena of facilitation and depression of ganglionic transmission. The ratio of the amplitude of the second of a depression of ganglionic transmission. The ratio of the amplitude of the second of a pair of EPSPs divided by the first was compared to the time interval between each pair of EPSPs divided by the first was compared to the time interval between each pulse. These ratios demonstrated two phases: an earlier phase of facilitation (20-500 msec pulse intervals) and a later phase of depression (500 msec-10 sec). Additional parameters-rate of rise of synaptic potentials (dV/dt), synaptic currents (EPSCs), and synaptic conductances (Gtr)-were determined and all confirmed the results obtained with EPSPs. Furthermore, the degree of facilitation or depression could be modulated by altering the extracellular concentration of calcium. On the other hand, comparison of the amplitude of pairs of presynaptic terminal spikes did not show any variability over similar stimulus intervals, nor were the amplitudes of miniature EPSPs significantly different before or after an evoked EPSP. Therefore, the processes of facilitation and depression of ganglionic transmission occur as a result of normal nerve terminal activity. The processes are occurring simultaneously, such that one or the other may predominate depending upon the interval between pulses, as well as the relative concentration of extracellular calcium."}
{"id": "PMID:186161", "title": "Localization of active sites in the neuromuscular junction of the frog.", "content": "Spontaneous quantal discharges at the frog neuromuscular junction were simultaneously monitored with three glass microelectrodes. Two extracellular electrodes were located at the synaptic cleft a few microns apart from each other so that each quantal discharge occurring nearby evoked signals in both electrodes. From the observed ratios of the signal amplitudes it is inferred that quantal discharges exclusively occur at discrete sites. The distance between active sites is in the same range as that between \"active zones\" seen from electron micrographs.", "contents": "Localization of active sites in the neuromuscular junction of the frog. Spontaneous quantal discharges at the frog neuromuscular junction were simultaneously monitored with three glass microelectrodes. Two extracellular electrodes were located at the synaptic cleft a few microns apart from each other so that each quantal discharge occurring nearby evoked signals in both electrodes. From the observed ratios of the signal amplitudes it is inferred that quantal discharges exclusively occur at discrete sites. The distance between active sites is in the same range as that between \"active zones\" seen from electron micrographs."}
{"id": "PMID:186164", "title": "Radiogenic free radicals in apatite: the influence of fluoride and hydroxide.", "content": "Fluor-hydroxyapatites of varying fluoride and hydroxide contents were irradiated by soft x-rays at -188 degrees C and examined by means of electron spin resonance spectroscopy. Variation in fluoride-hydroxide contents affected radical yield and resulted in the observation of two kinds of oxygen anion resonances: a doublet due to hydrogen hyperfine splitting and a singlet. At higher temperatures a spin transfer process became operative which enhanced the oxygen anion radical population. Increasing fluoride content was paralleled by decreasing g-values for the oxygen anion resonances, possibly attributable to increased delocalization of the unpaired spin.", "contents": "Radiogenic free radicals in apatite: the influence of fluoride and hydroxide. Fluor-hydroxyapatites of varying fluoride and hydroxide contents were irradiated by soft x-rays at -188 degrees C and examined by means of electron spin resonance spectroscopy. Variation in fluoride-hydroxide contents affected radical yield and resulted in the observation of two kinds of oxygen anion resonances: a doublet due to hydrogen hyperfine splitting and a singlet. At higher temperatures a spin transfer process became operative which enhanced the oxygen anion radical population. Increasing fluoride content was paralleled by decreasing g-values for the oxygen anion resonances, possibly attributable to increased delocalization of the unpaired spin."}
{"id": "PMID:186165", "title": "Evidence against the involvement of adenosine 3',5'-cyclic monophosphate in glucose inhibition of beta-galactosidase induction in Bacillus megaterium.", "content": "When Bacillus megaterium cells are grown on D-galactose as the sole carbon source, the cells actively synthesize beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23). However, D-galactose, when added to a glucose-grown culture, did not induce beta-galactosidase, apparently because of the glucose inhibition of the transport of galactose. On the other hand, when glucose was added to a galactose-grown culture, the transport of galactose continued at  a reduced but significate rate, whereas further synthesis of beta-galactosidase was halted. Adenosine 3',5'-cyclic monophosphate (camp) or guanosine 3',5'-cyclic monophosphate (Cgmp) did not relieve the glucose inhibition of beta-galactosidase synthesis in the preinduced culture. A method which gave a reproducible assay of c[32P]AMP in Escherichia coli did not detect cAMP or cGMP in a B. megaterium culture undergoing beta-galactosidase induction, but revealed the extracellular accumulation of two unknown phosphorylated compounds. Cell-free extracts prepared from galactose-grown cells did not catalyze the degradation of cAMP or cGMP.", "contents": "Evidence against the involvement of adenosine 3',5'-cyclic monophosphate in glucose inhibition of beta-galactosidase induction in Bacillus megaterium. When Bacillus megaterium cells are grown on D-galactose as the sole carbon source, the cells actively synthesize beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23). However, D-galactose, when added to a glucose-grown culture, did not induce beta-galactosidase, apparently because of the glucose inhibition of the transport of galactose. On the other hand, when glucose was added to a galactose-grown culture, the transport of galactose continued at  a reduced but significate rate, whereas further synthesis of beta-galactosidase was halted. Adenosine 3',5'-cyclic monophosphate (camp) or guanosine 3',5'-cyclic monophosphate (Cgmp) did not relieve the glucose inhibition of beta-galactosidase synthesis in the preinduced culture. A method which gave a reproducible assay of c[32P]AMP in Escherichia coli did not detect cAMP or cGMP in a B. megaterium culture undergoing beta-galactosidase induction, but revealed the extracellular accumulation of two unknown phosphorylated compounds. Cell-free extracts prepared from galactose-grown cells did not catalyze the degradation of cAMP or cGMP."}
{"id": "PMID:186166", "title": "Effects of an ATP analogue (alpha,beta-methylene-adenosine-5'-triphosphate) on cyclic AMP and cyclic GMP levels, 45Ca efflux, and protein secretion from rat pancreas.", "content": "The effects of the alpha,beta-methylene analogue of ATP (Ap(CH2)pp), described as a competitive inhibitor of adenylate cyclase (EC 4.6.1.1), were studied in the rat pancreas in vitro. The analogue did not alter basal cyclic AMP production and basal or carbachol-stimulated efflux of 45Ca from isotope-preloaded glands. On the other hand, Ap(CH2)pp reduced the secretory responses to carbachol, carbachol in the presence of dibutyryl cyclic AMP, pancreozymin (PZ), and the calcium ionophore, A-23187. Release of pancreatic protein in response to dibutyryl cyclic AMP itself was unaffected by the ATP analogue, suggesting that the other secretagogues tested share a common, Ap(CH2)pp-inhibitable pathway in their respective stimulatory actions. Though carbachol, PZ, and A-23187 all stimulated a rapid production (30 s) of pancreatic cyclic GMP, these responses were not affected by Ap(CH2)pp. Additional studies with the analogue indicated that it has a slow onset of action (30-45 min), i.e., its effect on secretion is preceded by secretagogue-induced changes in nucleotide levels and calcium efflux. Nonetheless, the analogue may affect cellular calcium homeostasis, if not during the initial events triggering secretion then during those events which maintain continued secretory output in the presence of a stimulus.", "contents": "Effects of an ATP analogue (alpha,beta-methylene-adenosine-5'-triphosphate) on cyclic AMP and cyclic GMP levels, 45Ca efflux, and protein secretion from rat pancreas. The effects of the alpha,beta-methylene analogue of ATP (Ap(CH2)pp), described as a competitive inhibitor of adenylate cyclase (EC 4.6.1.1), were studied in the rat pancreas in vitro. The analogue did not alter basal cyclic AMP production and basal or carbachol-stimulated efflux of 45Ca from isotope-preloaded glands. On the other hand, Ap(CH2)pp reduced the secretory responses to carbachol, carbachol in the presence of dibutyryl cyclic AMP, pancreozymin (PZ), and the calcium ionophore, A-23187. Release of pancreatic protein in response to dibutyryl cyclic AMP itself was unaffected by the ATP analogue, suggesting that the other secretagogues tested share a common, Ap(CH2)pp-inhibitable pathway in their respective stimulatory actions. Though carbachol, PZ, and A-23187 all stimulated a rapid production (30 s) of pancreatic cyclic GMP, these responses were not affected by Ap(CH2)pp. Additional studies with the analogue indicated that it has a slow onset of action (30-45 min), i.e., its effect on secretion is preceded by secretagogue-induced changes in nucleotide levels and calcium efflux. Nonetheless, the analogue may affect cellular calcium homeostasis, if not during the initial events triggering secretion then during those events which maintain continued secretory output in the presence of a stimulus."}
{"id": "PMID:186167", "title": "Preparation and characterization of adrenocortical plasma membrane angiotensin II receptors.", "content": "A bovine adrenocortical particulate fraction prepared by zonal ultracentrifugation and banding between rho20 1.08 and 1.101 in a linear sucrose gradient bound 7.3 times more [3H]angiotensin II (ATII) per milligram protein than the original homogenate. Enzyme marker and electron microscope studies indicated that this fraction was largely devoid of mitochondria while being enriched in smooth membranes of predominantly plasmalemmal origin. The binding of labeled ATII was maximal after 10 min incubation (22degreesC) and remained at equilibrium for at least 20 min thereafter. [3H]ATII binding was completely inhibited by saturating concentrations of nonradioactive ATII. The high-affinity binding site in the preparation had a specific binding capacity of 2.38 pmol-mg-1, with an equilibrium constant of 2.36 x 10(8) M(-1). Inhibition-displacement studies with unlabeled ATI,ATII,ATII fragments, analogs, and antagonists show that the receptor fraction has the highest affinity for the intact native octapeptide. ACTH and bradykinin had no specific effects on [3H]ATII binding. The current study suggests that the receptor fraction may be of use in a highly sensitive ATII radioligand assay.", "contents": "Preparation and characterization of adrenocortical plasma membrane angiotensin II receptors. A bovine adrenocortical particulate fraction prepared by zonal ultracentrifugation and banding between rho20 1.08 and 1.101 in a linear sucrose gradient bound 7.3 times more [3H]angiotensin II (ATII) per milligram protein than the original homogenate. Enzyme marker and electron microscope studies indicated that this fraction was largely devoid of mitochondria while being enriched in smooth membranes of predominantly plasmalemmal origin. The binding of labeled ATII was maximal after 10 min incubation (22degreesC) and remained at equilibrium for at least 20 min thereafter. [3H]ATII binding was completely inhibited by saturating concentrations of nonradioactive ATII. The high-affinity binding site in the preparation had a specific binding capacity of 2.38 pmol-mg-1, with an equilibrium constant of 2.36 x 10(8) M(-1). Inhibition-displacement studies with unlabeled ATI,ATII,ATII fragments, analogs, and antagonists show that the receptor fraction has the highest affinity for the intact native octapeptide. ACTH and bradykinin had no specific effects on [3H]ATII binding. The current study suggests that the receptor fraction may be of use in a highly sensitive ATII radioligand assay."}
{"id": "PMID:186168", "title": "Nasopharyngeal carcinoma and Burkitt's lymphoma in a Canadian family. I. HLA typing, EBV antibodies and serum immunoglobulins.", "content": "Two nasopharyngeal carcinomas of the lymphoepithelioma type and two Burkitt's lymphomas with the characteristic histopathologic features developed in three siblings and one first-degree cousin in a large French-Canadian family. Epstein-Barr virus antibody titres in the two lymphoepithelioma cases but not in the Burkitt's lymphoma cases were, as expected, greatly elevated. HLA typing of the family members failed to disclose HLA antigens A2 and B Sin-2, which have been associated with lymphoepithelioma in Asia. The occurrence, however, of a plasmacytoma in one other first-degree cousin and low serum IgA values in several siblings and cousins suggests the possibility of a genetically determined predisposing B-cell dysfunction in the development of these tumours.", "contents": "Nasopharyngeal carcinoma and Burkitt's lymphoma in a Canadian family. I. HLA typing, EBV antibodies and serum immunoglobulins. Two nasopharyngeal carcinomas of the lymphoepithelioma type and two Burkitt's lymphomas with the characteristic histopathologic features developed in three siblings and one first-degree cousin in a large French-Canadian family. Epstein-Barr virus antibody titres in the two lymphoepithelioma cases but not in the Burkitt's lymphoma cases were, as expected, greatly elevated. HLA typing of the family members failed to disclose HLA antigens A2 and B Sin-2, which have been associated with lymphoepithelioma in Asia. The occurrence, however, of a plasmacytoma in one other first-degree cousin and low serum IgA values in several siblings and cousins suggests the possibility of a genetically determined predisposing B-cell dysfunction in the development of these tumours."}
{"id": "PMID:186169", "title": "Nephrotoxic and cytoproliferative effects of streptozotocin: report of a patient with multiple hormone-secreting islet cell carcinoma.", "content": "The nephrotoxic and cytoproliferative side effects observed in a patient with Streptozotocin-treated, multiple hormone-secreting, pancreatic islet cell carcinoma are described. Streptozotocin induced prolonged partial remission of the patient's multiendocrine syndrome but resulted in progressive azotemia, which was controlled by temporary hemodialysis. A renal biopsy, the first to be reported in detail in such a condition, demonstrated a tubulo-interstitial nephritis and a glomerular alteration consisting of cellular nodules. At autopsy there were numerous bilateral renal cortical spindle cell \"tumors\" and cellular aggregates in glomeruli. These findings suggest that the tumorigenic effects of Streptozotocin demonstrated in animals may also occur in man.", "contents": "Nephrotoxic and cytoproliferative effects of streptozotocin: report of a patient with multiple hormone-secreting islet cell carcinoma. The nephrotoxic and cytoproliferative side effects observed in a patient with Streptozotocin-treated, multiple hormone-secreting, pancreatic islet cell carcinoma are described. Streptozotocin induced prolonged partial remission of the patient's multiendocrine syndrome but resulted in progressive azotemia, which was controlled by temporary hemodialysis. A renal biopsy, the first to be reported in detail in such a condition, demonstrated a tubulo-interstitial nephritis and a glomerular alteration consisting of cellular nodules. At autopsy there were numerous bilateral renal cortical spindle cell \"tumors\" and cellular aggregates in glomeruli. These findings suggest that the tumorigenic effects of Streptozotocin demonstrated in animals may also occur in man."}
{"id": "PMID:186170", "title": "Effect of oral prophylactic broad spectrum nonabsorbable antibiotics on the gastrointestinal absorption of nutrients and methotrexate in small cell bronchogenic carcinoma patients.", "content": "Patients with small cell bronchogenic carcinoma, in a study utilizing laminar-air-flow-protected environments, oral prophylactic broad spectrum non-absorbable antibiotics (PNAA), and intensive combination chemotherapy, were examined to determine the effects of PNAA on serum biochemical values and on gastrointestinal absorption of both nutrients and methotrexate. With use of PNAA the following abnormalities were observed; serum carotene and folate decreased, D-xylose absorption was impaired, fat globules and muscle fibers were demonstrable in the stool, and the mean weight loss in 6 weeks was 10.2% as compared with 4.3% in patients not treated with antibiotics. Methotrexate absorption decreased from a mean of 69% prior to antibiotic use to 44% on PNAA. Thus, PNAA causes malabsorption of both nutrients and drugs. It appears unwise to treat patients on PNAA with oral antineoplastic drugs. Nutritional status must also be closely monitored and supplemental nutrition, either intravenously or with elemental diets, must be considered.", "contents": "Effect of oral prophylactic broad spectrum nonabsorbable antibiotics on the gastrointestinal absorption of nutrients and methotrexate in small cell bronchogenic carcinoma patients. Patients with small cell bronchogenic carcinoma, in a study utilizing laminar-air-flow-protected environments, oral prophylactic broad spectrum non-absorbable antibiotics (PNAA), and intensive combination chemotherapy, were examined to determine the effects of PNAA on serum biochemical values and on gastrointestinal absorption of both nutrients and methotrexate. With use of PNAA the following abnormalities were observed; serum carotene and folate decreased, D-xylose absorption was impaired, fat globules and muscle fibers were demonstrable in the stool, and the mean weight loss in 6 weeks was 10.2% as compared with 4.3% in patients not treated with antibiotics. Methotrexate absorption decreased from a mean of 69% prior to antibiotic use to 44% on PNAA. Thus, PNAA causes malabsorption of both nutrients and drugs. It appears unwise to treat patients on PNAA with oral antineoplastic drugs. Nutritional status must also be closely monitored and supplemental nutrition, either intravenously or with elemental diets, must be considered."}
{"id": "PMID:186171", "title": "Small cell nonkeratinizing carcinoma of the cervix associated with ACTH production.", "content": "The case of a 40-year-old woman with primary small cell carcinoma of the cervix is reported. She developed widespread metastates and florid Cushing's syndrome. Serum ACTH levels were greatly elevated and no site of production other than the tumor could be demonstrated at autopsy. The tumor cells demonstrated features characteristic of cells of the APUD series. Such cells have been demonstrated in normal cervical epithelium; it is likely that they may become malignant, giving rise to tumors with a potential to secrete polypeptide hormones. This case suggests that endocrine active \"Apudomas\" may arise from the uterine cervix. Certainly, patients with small cell carcinoma of the cervix should be investigated with appropriate serum assays for polypeptide hormones.", "contents": "Small cell nonkeratinizing carcinoma of the cervix associated with ACTH production. The case of a 40-year-old woman with primary small cell carcinoma of the cervix is reported. She developed widespread metastates and florid Cushing's syndrome. Serum ACTH levels were greatly elevated and no site of production other than the tumor could be demonstrated at autopsy. The tumor cells demonstrated features characteristic of cells of the APUD series. Such cells have been demonstrated in normal cervical epithelium; it is likely that they may become malignant, giving rise to tumors with a potential to secrete polypeptide hormones. This case suggests that endocrine active \"Apudomas\" may arise from the uterine cervix. Certainly, patients with small cell carcinoma of the cervix should be investigated with appropriate serum assays for polypeptide hormones."}
{"id": "PMID:186172", "title": "Ultrastructural, histochemical, and biochemical studies of two cases with amylase, ACTH, and beta-MSH producing tumor.", "content": "Two cases of intrathoracic tumor, different in histology and accompanied by hyperamylasemia, were studied ultrastructurally, histochemically, and biochemically. The ultrastructure of the tumor cell cytoplasm showed many zymogen granules in case 1 and smaller cored granules in addition to zymogen granules in case 2. Both tumors contained not only a large amount of amylase, which was electrophoretically of saliva type with three components, but also significant amounts of immunoreactive ACTH and beta-MSH. Starch film and immunofluorescence showed that the tumor cells stored amylase. It was concluded from these findings that the tumor cells ectopically producing amylase, which showed differentiation toward the cells with zymogen production, could differentiate toward the cells of ACTH-MSH system at the same time.", "contents": "Ultrastructural, histochemical, and biochemical studies of two cases with amylase, ACTH, and beta-MSH producing tumor. Two cases of intrathoracic tumor, different in histology and accompanied by hyperamylasemia, were studied ultrastructurally, histochemically, and biochemically. The ultrastructure of the tumor cell cytoplasm showed many zymogen granules in case 1 and smaller cored granules in addition to zymogen granules in case 2. Both tumors contained not only a large amount of amylase, which was electrophoretically of saliva type with three components, but also significant amounts of immunoreactive ACTH and beta-MSH. Starch film and immunofluorescence showed that the tumor cells stored amylase. It was concluded from these findings that the tumor cells ectopically producing amylase, which showed differentiation toward the cells with zymogen production, could differentiate toward the cells of ACTH-MSH system at the same time."}
{"id": "PMID:186173", "title": "Carcinosarcoma and mixed m\u00fcllerian tumors of the fallopian tube: report of four cases.", "content": "We report a 74-year-old woman with malignant mixed m\u00fcllerian tumor and three women, aged 47, 58, and 76 years, with carcinosarcomas, all primary in the fallopian tube. The tumors grew predominantly intraluminally and were associated with hydrosalpinx. All four patients underwent salpingectomy. Two of them received radiation therapy; one died within 9 months because of the tumor and the second is well 2 years after diagnosis. Of the two women without additional therapy, one is alive with tumor 53 months postoperatively and the other is well 1 year after surgery. Available data suggest that these neoplasms are relatively radioresistant and that their prognosis correlates best with local invasiveness.", "contents": "Carcinosarcoma and mixed m\u00fcllerian tumors of the fallopian tube: report of four cases. We report a 74-year-old woman with malignant mixed m\u00fcllerian tumor and three women, aged 47, 58, and 76 years, with carcinosarcomas, all primary in the fallopian tube. The tumors grew predominantly intraluminally and were associated with hydrosalpinx. All four patients underwent salpingectomy. Two of them received radiation therapy; one died within 9 months because of the tumor and the second is well 2 years after diagnosis. Of the two women without additional therapy, one is alive with tumor 53 months postoperatively and the other is well 1 year after surgery. Available data suggest that these neoplasms are relatively radioresistant and that their prognosis correlates best with local invasiveness."}
{"id": "PMID:186174", "title": "Carcinoma of the stomach in childhood.", "content": "A case of mucinous adenocarcinoma of the stomach is described in a 20-month-old child with a large abdominal mass. The lesion arose from the lesser curvature of the stomach and invaded the submucosa and lymphatic channels. A partial response to chemotherapy, including vincristine, Cytoxan, actinomycin D, and adriamycin, was noted, but the patient died 3 1/2 months following diagnosis shortly after gastric perforation and peritonitis developed. Autopsy revealed a pattern of widespread visceral metastases, accompanied by pathologic findings suggestive of ataxia-telangiectasia. A diagnosis of mucinous adenocarcinoma, although it is rare, should be considered in the evaluation of primary neoplasms of the stomach in children.", "contents": "Carcinoma of the stomach in childhood. A case of mucinous adenocarcinoma of the stomach is described in a 20-month-old child with a large abdominal mass. The lesion arose from the lesser curvature of the stomach and invaded the submucosa and lymphatic channels. A partial response to chemotherapy, including vincristine, Cytoxan, actinomycin D, and adriamycin, was noted, but the patient died 3 1/2 months following diagnosis shortly after gastric perforation and peritonitis developed. Autopsy revealed a pattern of widespread visceral metastases, accompanied by pathologic findings suggestive of ataxia-telangiectasia. A diagnosis of mucinous adenocarcinoma, although it is rare, should be considered in the evaluation of primary neoplasms of the stomach in children."}
{"id": "PMID:186175", "title": "The morphology of tumors of the human gastrointestinal tract in short-term organ culture and the reaction of these tumors to infection with poliovirus.", "content": "A morphologic study of 57 cancers of the human gastrointestinal tract maintained in short-term organ culture was carried out, and the response of part of these tumors to infection with poliovirus was studied. The tumors, grown in vitro, mainly retained their original characteristics and histologic types. A certain correlation between the histologic type and its viability in short-term organ culture was revealed: the more differentiated forms were maintained better than the poorly differentiated ones. A comparative study of the polio-virus-infected and the control cultures indicated that wild poliovirus showed the most marked oncolytic activity in short-term organ culture, whereas attenuated poliovirus III produced a less marked, although still distinct, destructive effect.", "contents": "The morphology of tumors of the human gastrointestinal tract in short-term organ culture and the reaction of these tumors to infection with poliovirus. A morphologic study of 57 cancers of the human gastrointestinal tract maintained in short-term organ culture was carried out, and the response of part of these tumors to infection with poliovirus was studied. The tumors, grown in vitro, mainly retained their original characteristics and histologic types. A certain correlation between the histologic type and its viability in short-term organ culture was revealed: the more differentiated forms were maintained better than the poorly differentiated ones. A comparative study of the polio-virus-infected and the control cultures indicated that wild poliovirus showed the most marked oncolytic activity in short-term organ culture, whereas attenuated poliovirus III produced a less marked, although still distinct, destructive effect."}
{"id": "PMID:186176", "title": "Lymph node involvement by direct extension in adenoid cystic carcinoma. Absence of classic embolic lymph node metastasis.", "content": "Thirty-four cases of adenoid cyctic carcinoma seen at the University of Virginia Hospital from 1946 to 1974 were reviewed, with special emphasis on lymph node involvement by tumor. Lymph node involvement was found in three cases of primary tumors of the submaxillary gland, and all of the affected lymph nodes were in the immediate vicinity of the primary tumor. Two lymph nodes were involved in two of the cases, and one node was involved in the third case. In all of these lymph nodes, adenoid cystic carcinoma was present in the soft tissue surrounding the node, and the tumor extended into the node. No metastatic tumors were observed in 46 lymph nodes removed incidentally at the time of local excision of the primary tumors in 10 additional cases or in 212 lymph nodes examined after unilateral radical neck dissections in six other cases. Five autopsies in this series showed no lymph node metastases. In this series of cases adenoid cystic carcinoma only invades lymph nodes in the immediate vicinity of the primary tumor. When lymph node involvement does occur, it does not result from embolic lymph node metastasis; rather, a direct invasion of the lymph node from tumor in the perinodal soft tissue occurs. Obviously, this small study does not completely exclude the possibility of embolic metastasis; however, if it does occur, it must be extremely rare.", "contents": "Lymph node involvement by direct extension in adenoid cystic carcinoma. Absence of classic embolic lymph node metastasis. Thirty-four cases of adenoid cyctic carcinoma seen at the University of Virginia Hospital from 1946 to 1974 were reviewed, with special emphasis on lymph node involvement by tumor. Lymph node involvement was found in three cases of primary tumors of the submaxillary gland, and all of the affected lymph nodes were in the immediate vicinity of the primary tumor. Two lymph nodes were involved in two of the cases, and one node was involved in the third case. In all of these lymph nodes, adenoid cystic carcinoma was present in the soft tissue surrounding the node, and the tumor extended into the node. No metastatic tumors were observed in 46 lymph nodes removed incidentally at the time of local excision of the primary tumors in 10 additional cases or in 212 lymph nodes examined after unilateral radical neck dissections in six other cases. Five autopsies in this series showed no lymph node metastases. In this series of cases adenoid cystic carcinoma only invades lymph nodes in the immediate vicinity of the primary tumor. When lymph node involvement does occur, it does not result from embolic lymph node metastasis; rather, a direct invasion of the lymph node from tumor in the perinodal soft tissue occurs. Obviously, this small study does not completely exclude the possibility of embolic metastasis; however, if it does occur, it must be extremely rare."}
{"id": "PMID:186177", "title": "Hodgkin's disease and granulomatous angiitis of the central nervous system.", "content": "Granulomatous angiitis of the central nervous system, a pathologic entity associated previously with a fatal prognosis, is reported in a patient with Hodgkin's disease. Viral isolation, indirect fluorescent antibody, and electron microscopic studies performed on fresh cerebral tissue were negative. The granulomatous angiitis of the central nervous system in this patient remitted following therapy for Hodgkin's disease. The epidemiologic, clinical and pathologic data in all reported cases of granulomatous angiitis of the central nervous system suggest that it: 1) may have more than one etiology; 2) may not always be fatal; 3) is associated with varicella-zoster virus and Hodgkin's disease; 4) is one of two granulomatous reactions found in association with Hodgkin's disease; and when found with Hodgkin's disease, 5) may remit with adequate therapy for the lymphoma.", "contents": "Hodgkin's disease and granulomatous angiitis of the central nervous system. Granulomatous angiitis of the central nervous system, a pathologic entity associated previously with a fatal prognosis, is reported in a patient with Hodgkin's disease. Viral isolation, indirect fluorescent antibody, and electron microscopic studies performed on fresh cerebral tissue were negative. The granulomatous angiitis of the central nervous system in this patient remitted following therapy for Hodgkin's disease. The epidemiologic, clinical and pathologic data in all reported cases of granulomatous angiitis of the central nervous system suggest that it: 1) may have more than one etiology; 2) may not always be fatal; 3) is associated with varicella-zoster virus and Hodgkin's disease; 4) is one of two granulomatous reactions found in association with Hodgkin's disease; and when found with Hodgkin's disease, 5) may remit with adequate therapy for the lymphoma."}
{"id": "PMID:186178", "title": "An immunoelectron microscopic analysis of Epstein-Barr virus-associated complement-fixing antigen.", "content": "Epstein-Barr virus-associated, complement-fixing antigens have been observed with a complement-mediating immunoreaction and with the peroxidase-labeled anticomplement antibody electron microscopic method. Postive reaction products could be found in the nuclei of P3HR-1 cell lines. At high magnification, it was ascertained that the reaction-positive precipitates were associated with chromatin and were mostly either finely granular or filamentous, which suggests that the antigen was not uniform. It was speculated that the antigen would be analogous to the SV40 T-antigen, since the localization pattern of the positive reaction was similar in both antigens. This new, modified method using complement may also be used for detection of a natural antibody of unknown class or for low-sensitivity systems of antigen-antibody reactions. Thus, this method appears useful for studying various kinds of experimental materials.", "contents": "An immunoelectron microscopic analysis of Epstein-Barr virus-associated complement-fixing antigen. Epstein-Barr virus-associated, complement-fixing antigens have been observed with a complement-mediating immunoreaction and with the peroxidase-labeled anticomplement antibody electron microscopic method. Postive reaction products could be found in the nuclei of P3HR-1 cell lines. At high magnification, it was ascertained that the reaction-positive precipitates were associated with chromatin and were mostly either finely granular or filamentous, which suggests that the antigen was not uniform. It was speculated that the antigen would be analogous to the SV40 T-antigen, since the localization pattern of the positive reaction was similar in both antigens. This new, modified method using complement may also be used for detection of a natural antibody of unknown class or for low-sensitivity systems of antigen-antibody reactions. Thus, this method appears useful for studying various kinds of experimental materials."}
{"id": "PMID:186179", "title": "Radical partial renal irradiation. an alternative to partial nephrectomy in bilateral Wilms' tumor.", "content": "A 6-year-old girl with simultaneous bilateral Wilms' tumor was treated with a radical nephrectomy on the side of more extensive involvement, followed by postoperative renal bed irradiation (3500 rads over 32 days) and radical partial renal irradiation (4000 rads over 35 days) to the contralateral disease. Concurrent and subsequent adjuvant actinomycin-D and vincristine were given. She has remained disease-free for over 5 years after primary therapy, with satisfactory renal function. This case report suggest that radical partial renal irradiation may be an alternative to partial nephrectomy in the management of the lesser involved kidney in some patients with bilateral Wilms' tumor.", "contents": "Radical partial renal irradiation. an alternative to partial nephrectomy in bilateral Wilms' tumor. A 6-year-old girl with simultaneous bilateral Wilms' tumor was treated with a radical nephrectomy on the side of more extensive involvement, followed by postoperative renal bed irradiation (3500 rads over 32 days) and radical partial renal irradiation (4000 rads over 35 days) to the contralateral disease. Concurrent and subsequent adjuvant actinomycin-D and vincristine were given. She has remained disease-free for over 5 years after primary therapy, with satisfactory renal function. This case report suggest that radical partial renal irradiation may be an alternative to partial nephrectomy in the management of the lesser involved kidney in some patients with bilateral Wilms' tumor."}
{"id": "PMID:186180", "title": "Calcium metabolism in cancer. Studies using calcium isotopes and immunoassays for parathyroid hormone and calcitonin.", "content": "Studies of calcium metabolism in 38 patients with cancer indicated that: 1) intestinal absorption of calcium was reduced in patients with skeletal metastases and in those with hypercalcemia; 2) calcium-47 space (a measurement of bone turnover rate) was high in the patients with skeletal metastases; 3) hypercalcemic patients had higher urinary and endogenous fecal excretion of calcium than those who were normocalcemic; 4) levels of plasma immunoreactive parathyroid hormone were similar in normo- and hypercalcemic patients, but the levels for a given serum calcium in malignant disease were lower than those in primary hyperparathyroidism; and 5) some patients had elevated calcitonin levels. Hypercalcemia complicating malignant disease is therefore not due to hyperabsorption or diminished excretion of calcium, and a low calcium diet is unlikely to benefit these patients. Measurement of 47Ca space could be of use in monitoring therapy of patients with skeletal metastases, and measurement of plasma parathyroid hormone could be useful in the differential diagnosis of hypercalcemia.", "contents": "Calcium metabolism in cancer. Studies using calcium isotopes and immunoassays for parathyroid hormone and calcitonin. Studies of calcium metabolism in 38 patients with cancer indicated that: 1) intestinal absorption of calcium was reduced in patients with skeletal metastases and in those with hypercalcemia; 2) calcium-47 space (a measurement of bone turnover rate) was high in the patients with skeletal metastases; 3) hypercalcemic patients had higher urinary and endogenous fecal excretion of calcium than those who were normocalcemic; 4) levels of plasma immunoreactive parathyroid hormone were similar in normo- and hypercalcemic patients, but the levels for a given serum calcium in malignant disease were lower than those in primary hyperparathyroidism; and 5) some patients had elevated calcitonin levels. Hypercalcemia complicating malignant disease is therefore not due to hyperabsorption or diminished excretion of calcium, and a low calcium diet is unlikely to benefit these patients. Measurement of 47Ca space could be of use in monitoring therapy of patients with skeletal metastases, and measurement of plasma parathyroid hormone could be useful in the differential diagnosis of hypercalcemia."}
{"id": "PMID:186184", "title": "Cyclic AMP as a determinant of vulnerability to ventricular fibrillation in the isolated rat heart.", "content": "Ventricular fibrillation threshold and vulnerable period were measured in the isolated perfused rat heart to assess the influence of dibutyryl cyclic AMP on ventricular vulnerability. Doses of dibutyryl cyclic AMP of 0.6-1.6  mumol/min caused an increase in coronary flow but had no effect on vulnerability, whereas doses of 2.6-4.2 mumol/min resulted in an increase in coronary flow, a decrease in VF threshold, and an increase in the width of the vulnerable period. These experiments support the concept of a local myocardial action of catecholamines, mediated by cyclic AMP, whereby vulnerability to ventricular fibrillation is increased.", "contents": "Cyclic AMP as a determinant of vulnerability to ventricular fibrillation in the isolated rat heart. Ventricular fibrillation threshold and vulnerable period were measured in the isolated perfused rat heart to assess the influence of dibutyryl cyclic AMP on ventricular vulnerability. Doses of dibutyryl cyclic AMP of 0.6-1.6  mumol/min caused an increase in coronary flow but had no effect on vulnerability, whereas doses of 2.6-4.2 mumol/min resulted in an increase in coronary flow, a decrease in VF threshold, and an increase in the width of the vulnerable period. These experiments support the concept of a local myocardial action of catecholamines, mediated by cyclic AMP, whereby vulnerability to ventricular fibrillation is increased."}
{"id": "PMID:186185", "title": "[Polymorphism of granular endoplasmic reticulum in the ovocytes of Mytilus edulis L].", "content": "In the cytoplasm of the ovocytes of Mytilus edulis, at the beginning of the yolk elaboration, but especially at the end of vitellogenesis, the polymorphous rough endoplasmic reticulum is very well developed. The concentrical disposition of the cisternae around of the mitochondria, the lipid inclusions and some granules of the yolk, are very frequent and must be considered as a system for increasing the area of proteic synthesis.", "contents": "[Polymorphism of granular endoplasmic reticulum in the ovocytes of Mytilus edulis L]. In the cytoplasm of the ovocytes of Mytilus edulis, at the beginning of the yolk elaboration, but especially at the end of vitellogenesis, the polymorphous rough endoplasmic reticulum is very well developed. The concentrical disposition of the cisternae around of the mitochondria, the lipid inclusions and some granules of the yolk, are very frequent and must be considered as a system for increasing the area of proteic synthesis."}
{"id": "PMID:186186", "title": "[Spontaneous and induced sterility by ethyl methanesulfonate (EMS) in Nigella damascena L].", "content": "EMS-induced sterility could be very partially due to chromosomal aberrations appearing during male and female meiosis or even to mechanical abnormalities of the double fertilization. The sterility could be also related to diplontic origin (lethal factors or small deficiencies appearing in homozygous state on account of self-pollinization). Owing to our histological and genetical data, a female gametophytic origin could be mainly ascribed to EMS induced sterility. It could arise from a damage of the feeding function of the nucellus.", "contents": "[Spontaneous and induced sterility by ethyl methanesulfonate (EMS) in Nigella damascena L]. EMS-induced sterility could be very partially due to chromosomal aberrations appearing during male and female meiosis or even to mechanical abnormalities of the double fertilization. The sterility could be also related to diplontic origin (lethal factors or small deficiencies appearing in homozygous state on account of self-pollinization). Owing to our histological and genetical data, a female gametophytic origin could be mainly ascribed to EMS induced sterility. It could arise from a damage of the feeding function of the nucellus."}
{"id": "PMID:186187", "title": "Alterations in the neurohypophysis of rats treated with chlorphentermine or tricyclic antidepressants.", "content": "Rats were treated with several amphiphilic, cationic compounds that are known to cause generalized lipidosis (chlorphentermine, iprindole, 1-chloro-amitriptyline, clomipramine). After prolonged drug treatment the neurohypophysis showed severe morphologic alterations particularly in Herring bodies (HB), perivascular cells, and pituicytes. HBs displayed the following abnormalities: (a) great accumulation of autophagic vacuoles that contained neurosecretory granules (NSG); (b) numerous coarse osmiophilic conglomerates; (c) masses of multilamellated material; (d) reduced numbers of intact NSGs. Perivascular cells accumulated large lamellated inclusion bodies. Pituicytes contained membrane-bound crystalloid inclusion bodies. The noxious effect of chlorphentermine and l-chloro-amitriptyline was more pronounced than that of iprindole and clomipramine. The alterations in perivascular cells and in pituicytes are typical of drug-induced lipidosis. The lesions in HBs are tentatively explained as follows: HBs were previously proposed to be the sites of normally occurring intraaxonal disposal of excess neurosecretory material. The present experimental conditions interfere with this catabolic process. Incomplete digestion of the axo-plasmic constituents due for disposal might result in abnormal accumulation of NSG-containing autophagic vacuoles, osmiophilic conglomerates, and multilamellated material. This eventually leads to degeneration of HBs. The functional implications of the neurohypophysial lesions remain to be elucidated by functional experiments.", "contents": "Alterations in the neurohypophysis of rats treated with chlorphentermine or tricyclic antidepressants. Rats were treated with several amphiphilic, cationic compounds that are known to cause generalized lipidosis (chlorphentermine, iprindole, 1-chloro-amitriptyline, clomipramine). After prolonged drug treatment the neurohypophysis showed severe morphologic alterations particularly in Herring bodies (HB), perivascular cells, and pituicytes. HBs displayed the following abnormalities: (a) great accumulation of autophagic vacuoles that contained neurosecretory granules (NSG); (b) numerous coarse osmiophilic conglomerates; (c) masses of multilamellated material; (d) reduced numbers of intact NSGs. Perivascular cells accumulated large lamellated inclusion bodies. Pituicytes contained membrane-bound crystalloid inclusion bodies. The noxious effect of chlorphentermine and l-chloro-amitriptyline was more pronounced than that of iprindole and clomipramine. The alterations in perivascular cells and in pituicytes are typical of drug-induced lipidosis. The lesions in HBs are tentatively explained as follows: HBs were previously proposed to be the sites of normally occurring intraaxonal disposal of excess neurosecretory material. The present experimental conditions interfere with this catabolic process. Incomplete digestion of the axo-plasmic constituents due for disposal might result in abnormal accumulation of NSG-containing autophagic vacuoles, osmiophilic conglomerates, and multilamellated material. This eventually leads to degeneration of HBs. The functional implications of the neurohypophysial lesions remain to be elucidated by functional experiments."}
{"id": "PMID:186188", "title": "Effect of collagenase on mechanical activity and fine structure of an intestinal smooth muscle.", "content": "The effect of the enzyme collagenase (40-200 units-ml-1) on the spontaneous mechanical activity in vitro and on the fine structure of the activity of the taenia was enhanced both in the isometric and isotonic recordings; after several minutes the muscles became slack or elongated to up to twice their resting lengths. The structural changes were dramatic but a number of muscle cells remained apparently unaltered even with the highest concentration and the longest incubation time (120 minutes). The large variety of structural changes were tentatively grouped into two separate sequences. One sequence involved swelling of the muscle cell, dispersion of the filaments and breaking up of the cell membrane: the thick myofilaments increased considerably in size and became heterogeneous in size and shape, but were still recognizable after disruption of the cell membrane. The other disruptive sequence involved separation of the superficial part of the muscle cell, which became electron-lucent, from the core of the cell where filaments were very densely packed. Few or no changes were observed in non-muscle cells.", "contents": "Effect of collagenase on mechanical activity and fine structure of an intestinal smooth muscle. The effect of the enzyme collagenase (40-200 units-ml-1) on the spontaneous mechanical activity in vitro and on the fine structure of the activity of the taenia was enhanced both in the isometric and isotonic recordings; after several minutes the muscles became slack or elongated to up to twice their resting lengths. The structural changes were dramatic but a number of muscle cells remained apparently unaltered even with the highest concentration and the longest incubation time (120 minutes). The large variety of structural changes were tentatively grouped into two separate sequences. One sequence involved swelling of the muscle cell, dispersion of the filaments and breaking up of the cell membrane: the thick myofilaments increased considerably in size and became heterogeneous in size and shape, but were still recognizable after disruption of the cell membrane. The other disruptive sequence involved separation of the superficial part of the muscle cell, which became electron-lucent, from the core of the cell where filaments were very densely packed. Few or no changes were observed in non-muscle cells."}
{"id": "PMID:186189", "title": "Extraneuronal effects of 6-hydroxydopamine and extraneuronal uptake of noradrenaline. In-vivo and in-vitro studies on adrenocortical cells of lizards and rats.", "content": "6-hydroxydopamine (6-OHDA) was shown to cause ultrastructural changes in adrenocortical cells of lizards and rats. These changes comprised the formation of dense bodies with lamellar and crystalloid patterns, a decrease in the number of mitochondria and structural alterations of mitochondria. Alterations in adrenomedullary cells were not affected as a rule. Only in young animals did 6-OHDA cause deposits of an electron-dense material in medullary cells. An attempt was made to obtain information on amine uptake into cortical cells using the Falck-Hillarp technique to analyse the in-vivo and in-vitro uptake of noradrenaline (NA) into the adrenal cortex in adult rats. Extraneuronal uptake into heart and spleen was studied as well. Our results suggest that NA is taken up into cortical cells, particularly into nuclei, after exposure to 10(-4) gm/ml in-vitro indicating that uptake of 6-OHDA is also likely. Investigations using labelled 6-OHDA is also likely. Investigations using labelled 6-OHDA are required for further elucidating its extraneuronal uptake.", "contents": "Extraneuronal effects of 6-hydroxydopamine and extraneuronal uptake of noradrenaline. In-vivo and in-vitro studies on adrenocortical cells of lizards and rats. 6-hydroxydopamine (6-OHDA) was shown to cause ultrastructural changes in adrenocortical cells of lizards and rats. These changes comprised the formation of dense bodies with lamellar and crystalloid patterns, a decrease in the number of mitochondria and structural alterations of mitochondria. Alterations in adrenomedullary cells were not affected as a rule. Only in young animals did 6-OHDA cause deposits of an electron-dense material in medullary cells. An attempt was made to obtain information on amine uptake into cortical cells using the Falck-Hillarp technique to analyse the in-vivo and in-vitro uptake of noradrenaline (NA) into the adrenal cortex in adult rats. Extraneuronal uptake into heart and spleen was studied as well. Our results suggest that NA is taken up into cortical cells, particularly into nuclei, after exposure to 10(-4) gm/ml in-vitro indicating that uptake of 6-OHDA is also likely. Investigations using labelled 6-OHDA is also likely. Investigations using labelled 6-OHDA are required for further elucidating its extraneuronal uptake."}
{"id": "PMID:186190", "title": "A multilamellate body in the granulated hypophysial cells of the teleost, Hemihaplochromis philander.", "content": "A multilamellate body (MLB), bearing close resemblance to an array of annulate lamellae, has been observed in several adenohypophysial cell types of the teleost, Hemihaplochromis philander. In longitudinal section, each MLB comprises a ladder-like row of 12-50 sausage-shaped profiles, termed lamellae. A few lamellae in each section show connections with the endoplasmic reticulum. Apposition of paired lamellar membranes at regularly spaced intervals results in a beaded appearance, whereby sites of membrane apposition are probable pore sites. The MLB differs from annulate lamellae in having poorly developed pores and closer packing of lamellae. It is suggested that the MLBs described here, may represent annulate lamellae at a stage of development or break-down when pores are incomplete.", "contents": "A multilamellate body in the granulated hypophysial cells of the teleost, Hemihaplochromis philander. A multilamellate body (MLB), bearing close resemblance to an array of annulate lamellae, has been observed in several adenohypophysial cell types of the teleost, Hemihaplochromis philander. In longitudinal section, each MLB comprises a ladder-like row of 12-50 sausage-shaped profiles, termed lamellae. A few lamellae in each section show connections with the endoplasmic reticulum. Apposition of paired lamellar membranes at regularly spaced intervals results in a beaded appearance, whereby sites of membrane apposition are probable pore sites. The MLB differs from annulate lamellae in having poorly developed pores and closer packing of lamellae. It is suggested that the MLBs described here, may represent annulate lamellae at a stage of development or break-down when pores are incomplete."}
{"id": "PMID:186191", "title": "Exocrine pancreas under experimental conditions. II. In vitro formation of paracrystalline structures and its functional consequences.", "content": "The in vitro formation of paracrystalline structures after addition of high concentrations of amino acids to the incubation medium was investigated in pancreatic lobules and pancreatic homogenates. It could be shown that even in the homogenate, pCPA induced the formation of paracrystalline structures which exhibited the same ultrastructural arrangement as seen in the in vivo induced paracrystalline inclusions in the RER of the rat pancreas. In correlation with the morphological alterations, the functional consequences to the secretory process, i.e. amylase discharge,discharge of pulse-labeled proteins and incorporation of 3H-leucine into pancreatic proteins,were studied in pancreaticlobules. Two different approaches were used. Firstly, the effect of pCPA-pretreatment of rats and secondly, the effect of higher pCPA concentrations in the incubation medium on the secretory process in untreated pancreatic lobules were studied. A nonparallelism of inhibition of the three different steps of the secretory process depending, with respect to its extent,on time after pCPA-application (4-72 h) and on the concentration of pCPA (1-10(-5) to 1-10(-2) M) in the incubation medium was found. In addition to specific effects probably due to pCPA and to the paracrystalline inclusions, unspecific alterations, particularly accompanying degenerative processes after in vivo pretreatment, could be differentiated.", "contents": "Exocrine pancreas under experimental conditions. II. In vitro formation of paracrystalline structures and its functional consequences. The in vitro formation of paracrystalline structures after addition of high concentrations of amino acids to the incubation medium was investigated in pancreatic lobules and pancreatic homogenates. It could be shown that even in the homogenate, pCPA induced the formation of paracrystalline structures which exhibited the same ultrastructural arrangement as seen in the in vivo induced paracrystalline inclusions in the RER of the rat pancreas. In correlation with the morphological alterations, the functional consequences to the secretory process, i.e. amylase discharge,discharge of pulse-labeled proteins and incorporation of 3H-leucine into pancreatic proteins,were studied in pancreaticlobules. Two different approaches were used. Firstly, the effect of pCPA-pretreatment of rats and secondly, the effect of higher pCPA concentrations in the incubation medium on the secretory process in untreated pancreatic lobules were studied. A nonparallelism of inhibition of the three different steps of the secretory process depending, with respect to its extent,on time after pCPA-application (4-72 h) and on the concentration of pCPA (1-10(-5) to 1-10(-2) M) in the incubation medium was found. In addition to specific effects probably due to pCPA and to the paracrystalline inclusions, unspecific alterations, particularly accompanying degenerative processes after in vivo pretreatment, could be differentiated."}
{"id": "PMID:186192", "title": "Extraneuronal effects of 6-hydroxydopamine. Tissue culture studies on adrenocortical cells of rats.", "content": "The effects of various concentrations of 6-hydroxydopamine (6-OHDA) on rat adrenocortical cells in tissue culture were studied with phase contrast and electron microscopy. With 40 mg/l of 6-OHDA the first signs of alteration as revealed by microcinematography appeared in isolated cortical cells as early as 15 min after addition of the drug. There was a cessation of movement of cell organelles and an immobilisation of membrane undulations followed by the development of dark inclusion bodies. The cells underwent increasing shrinkage and collapsed by 1 1/2 h. Chromaffin cells were not affected until 45 min after exposure to the drug and neurons were the most resistant population. However 6 1/2 h after application of the drug most cells in the culture were dead. 6-OHDA applied in different doses and to adrenal explants did not alter the sequence of events. Ultrastructurally cortex cells underwent damage alone two lines: they either showed lytic changes or developed various types of dense bodies before reaching the lytic stage. Treatment of cortical cells with 40 mg/l 5-or 6-OHDA followed by exposure to buffered 2% glyoxylic acid and heat did not produce a fluorescence within the cells. Microspectrofluorimetry on amine models with noradrenaline, 5- and 6-OHDA revealed that neither 5-nor 6-OHDA are capable to form a fluorophore with glyoxylic acid.", "contents": "Extraneuronal effects of 6-hydroxydopamine. Tissue culture studies on adrenocortical cells of rats. The effects of various concentrations of 6-hydroxydopamine (6-OHDA) on rat adrenocortical cells in tissue culture were studied with phase contrast and electron microscopy. With 40 mg/l of 6-OHDA the first signs of alteration as revealed by microcinematography appeared in isolated cortical cells as early as 15 min after addition of the drug. There was a cessation of movement of cell organelles and an immobilisation of membrane undulations followed by the development of dark inclusion bodies. The cells underwent increasing shrinkage and collapsed by 1 1/2 h. Chromaffin cells were not affected until 45 min after exposure to the drug and neurons were the most resistant population. However 6 1/2 h after application of the drug most cells in the culture were dead. 6-OHDA applied in different doses and to adrenal explants did not alter the sequence of events. Ultrastructurally cortex cells underwent damage alone two lines: they either showed lytic changes or developed various types of dense bodies before reaching the lytic stage. Treatment of cortical cells with 40 mg/l 5-or 6-OHDA followed by exposure to buffered 2% glyoxylic acid and heat did not produce a fluorescence within the cells. Microspectrofluorimetry on amine models with noradrenaline, 5- and 6-OHDA revealed that neither 5-nor 6-OHDA are capable to form a fluorophore with glyoxylic acid."}
{"id": "PMID:186193", "title": "Location of the sequences coding for capsid proteins VP1 and VP2 on polyoma virus DNA.", "content": "The 19S and 16S polyoma virus late mRNAs have been separated on sucrose-formamide density gradients and translated in vitro. The 16S RNA codes only for polyoma capsid protein VP1, while the 19S RNA codes in addition for capsid protein VP2. Since the 19S and 16S species have been previously mapped on the viral genome, these results allow us to deduce the location of the sequences coding for VP1 and VP2. Comparison of the chain lengths of the capsid proteins with the size of the viral mRNAs coding for them suggests that VP1 and VP2 are entirely virus-coded. Purified polyoma 19S RNA directs the synthesis of very little VP1 in vitro, although it contains all the sequences required to code for the protein. The initiation site for VP1 synthesis which is located at an internal position on the messenger is probably inactive either because it is inaccessible or because it lacks an adjacent \"capped\" 5' terminus. Similar inactive internal initiation sites have been reported for other eucarotic viral mRNAs (for example, Semliki forest virus, Brome mosaic virus, and tobacco mosaic virus), suggesting that while eucaryotic mRNAs may have more than one initiation site for protein synthesis, only those sites nearer the 5' terminus of the mRNA are active.", "contents": "Location of the sequences coding for capsid proteins VP1 and VP2 on polyoma virus DNA. The 19S and 16S polyoma virus late mRNAs have been separated on sucrose-formamide density gradients and translated in vitro. The 16S RNA codes only for polyoma capsid protein VP1, while the 19S RNA codes in addition for capsid protein VP2. Since the 19S and 16S species have been previously mapped on the viral genome, these results allow us to deduce the location of the sequences coding for VP1 and VP2. Comparison of the chain lengths of the capsid proteins with the size of the viral mRNAs coding for them suggests that VP1 and VP2 are entirely virus-coded. Purified polyoma 19S RNA directs the synthesis of very little VP1 in vitro, although it contains all the sequences required to code for the protein. The initiation site for VP1 synthesis which is located at an internal position on the messenger is probably inactive either because it is inaccessible or because it lacks an adjacent \"capped\" 5' terminus. Similar inactive internal initiation sites have been reported for other eucarotic viral mRNAs (for example, Semliki forest virus, Brome mosaic virus, and tobacco mosaic virus), suggesting that while eucaryotic mRNAs may have more than one initiation site for protein synthesis, only those sites nearer the 5' terminus of the mRNA are active."}
{"id": "PMID:186202", "title": "Homologous synthesis: a method for the preparation of mixed substrates and individual compounds.", "content": "Equimolar mixtures of several homologous or vinylogous alkyl methanesulfonates (mesylates) are converted, by a series of reactions, into equimolar mixtures of compounds having one methylene group more, per molecule, than the starting material. Such mixtures can be used for studying the specificity of an enzymatic reaction in a single experiment in vivo or in vitro. The simultaneous synthesis of a mixture of compounds is also of great advantage in the preparation of a series of radioactively labelled substances. It is more convenient and much more efficient to prepare several labelled compounds of a homologous or vinylogous series in a single reaction, and to isolate each of them by chromatographic methods, than to synthesize the individual substances separately.", "contents": "Homologous synthesis: a method for the preparation of mixed substrates and individual compounds. Equimolar mixtures of several homologous or vinylogous alkyl methanesulfonates (mesylates) are converted, by a series of reactions, into equimolar mixtures of compounds having one methylene group more, per molecule, than the starting material. Such mixtures can be used for studying the specificity of an enzymatic reaction in a single experiment in vivo or in vitro. The simultaneous synthesis of a mixture of compounds is also of great advantage in the preparation of a series of radioactively labelled substances. It is more convenient and much more efficient to prepare several labelled compounds of a homologous or vinylogous series in a single reaction, and to isolate each of them by chromatographic methods, than to synthesize the individual substances separately."}
{"id": "PMID:186203", "title": "Identification of isomeric doxyl stearic acids by gas-liquid chromatography and mass spectrometry.", "content": "Direct probe and GC/MS spectra were determined for the isomeric 4- to 16-doxyl stearic acids and their methyl and silyl esters in pure form and in mixture with natural fatty acids and their esters. The base peak for all free and esterified doxyl stearic acids was at m/e 281. The methyl esters of all isomers gave nearly identical fragments in the high mass regions having M+ at m/e 398 with intensities of 2-3%. The isomers were identified on the basis of the fragments retaining the doxyl group, which had positive charge and were different for each compound. It was shown that the fragment m/e 281 may be used to identify and quantitate the stearate derivatives in presence of natural fatty acids. The silyl esters of the doxyl stearates gave complex mass spectra. The isomeric doxyl stearates were resolved by GLC on 3 ft. glass columns containing 1% SE-30 packing as methyl esters.", "contents": "Identification of isomeric doxyl stearic acids by gas-liquid chromatography and mass spectrometry. Direct probe and GC/MS spectra were determined for the isomeric 4- to 16-doxyl stearic acids and their methyl and silyl esters in pure form and in mixture with natural fatty acids and their esters. The base peak for all free and esterified doxyl stearic acids was at m/e 281. The methyl esters of all isomers gave nearly identical fragments in the high mass regions having M+ at m/e 398 with intensities of 2-3%. The isomers were identified on the basis of the fragments retaining the doxyl group, which had positive charge and were different for each compound. It was shown that the fragment m/e 281 may be used to identify and quantitate the stearate derivatives in presence of natural fatty acids. The silyl esters of the doxyl stearates gave complex mass spectra. The isomeric doxyl stearates were resolved by GLC on 3 ft. glass columns containing 1% SE-30 packing as methyl esters."}
{"id": "PMID:186204", "title": "Isolation of a novel lipid hapten, cytolipin S, from rat spleen.", "content": "Antisera against rat erythrocytes contain agglutinins directed against unknown lipid determinants. Complement-fixation shows more reactivity with lipid extracts of rat spleen than of other rat tissues. The isolation of the reactive lipid from rat spleen, cytolipin S, is described. Cytolipin S is a glycosphingolipid containing glucose, galactose, and galactosamine with molar ratios of 1:2:1. It migrates on TLC like asialo GM1 (more slowly than cytolipin R, a ceramide tetrasaccharide, or cytolipin F, a ceramide pentasaccharide). Asialo GM1 and cytolipin S, when properly combined with auxiliary lipids, react very similarly with anti-rat erythrocyte sera by complement-fixation. However, cytolipin S is much more effective than asialo GM1 in inhibiting the hemagglutination reactions. It is concluded that cytolipin S and asialo GM1 are ceramide tetrasaccharides having different chemical structures and that the structural differences probably will be found in the carbohydrate linkages other than that between the terminal and penultimate residues.", "contents": "Isolation of a novel lipid hapten, cytolipin S, from rat spleen. Antisera against rat erythrocytes contain agglutinins directed against unknown lipid determinants. Complement-fixation shows more reactivity with lipid extracts of rat spleen than of other rat tissues. The isolation of the reactive lipid from rat spleen, cytolipin S, is described. Cytolipin S is a glycosphingolipid containing glucose, galactose, and galactosamine with molar ratios of 1:2:1. It migrates on TLC like asialo GM1 (more slowly than cytolipin R, a ceramide tetrasaccharide, or cytolipin F, a ceramide pentasaccharide). Asialo GM1 and cytolipin S, when properly combined with auxiliary lipids, react very similarly with anti-rat erythrocyte sera by complement-fixation. However, cytolipin S is much more effective than asialo GM1 in inhibiting the hemagglutination reactions. It is concluded that cytolipin S and asialo GM1 are ceramide tetrasaccharides having different chemical structures and that the structural differences probably will be found in the carbohydrate linkages other than that between the terminal and penultimate residues."}
{"id": "PMID:186205", "title": "An ESR study of the hydration steps of lecithin multilayers.", "content": "A spin-labeled stearic acid and other spin-labeled molecules have been used for an ESR study of the hydration process of the egg lecithin lamellar phase for water concentrations, CW greater than 10%. Two hydration steps are found for CW approximately 20% and CW congruent to 30%, in good agreement with results of the literature. To explain discontinuities in the behavior of three spin-labeled molecules at CW congruent to 20%, a conformational change of the phosphatidylcholine polar head and a phase transition in the polar interface are proposed.", "contents": "An ESR study of the hydration steps of lecithin multilayers. A spin-labeled stearic acid and other spin-labeled molecules have been used for an ESR study of the hydration process of the egg lecithin lamellar phase for water concentrations, CW greater than 10%. Two hydration steps are found for CW approximately 20% and CW congruent to 30%, in good agreement with results of the literature. To explain discontinuities in the behavior of three spin-labeled molecules at CW congruent to 20%, a conformational change of the phosphatidylcholine polar head and a phase transition in the polar interface are proposed."}
{"id": "PMID:186207", "title": "Potency of field samples of oral poliovirus vaccine.", "content": "The transport and storage facilities and the potency of oral poliovirus vaccines currently administered in 108 centres in India were investigated. Storage and distribution practices in many of the centres were far from ideal. There was no significant loss of potency in the vaccine samples collected from a few centres, while samples from other centres showed a 60-99% loss of virus particles per dose. A national monitoring system has since been established to check the potency of every batch of oral poliovirus vaccine imported and to streamline the transport, storage, and administration of the vaccine. Constant vigilance as regards the quality of vaccines should ensure the success of any poliomyelitis immunization campaign.", "contents": "Potency of field samples of oral poliovirus vaccine. The transport and storage facilities and the potency of oral poliovirus vaccines currently administered in 108 centres in India were investigated. Storage and distribution practices in many of the centres were far from ideal. There was no significant loss of potency in the vaccine samples collected from a few centres, while samples from other centres showed a 60-99% loss of virus particles per dose. A national monitoring system has since been established to check the potency of every batch of oral poliovirus vaccine imported and to streamline the transport, storage, and administration of the vaccine. Constant vigilance as regards the quality of vaccines should ensure the success of any poliomyelitis immunization campaign."}
{"id": "PMID:186208", "title": "Some characteristics of poliovirus strains isolated in Uganda between 1966 and 1971.", "content": "Sixty-five poliovirus strains were investigated in genetic marker tests in order to obtain information on the characteristics of polioviruses circulating in Uganda where, owing to the insufficient use of live poliovirus vaccine, poliomyelitis remained a serious public health problem. Of the type 1 strains predominant in both epidemic and non-epidemic years, 29 were studied for their antigenic fine structure. Based on their intratypic character, these strains proved to represent six different antigenic variants. Three of these variants were predominant during certain periods; the first variant was present in 1966 and 1968, the second in 1967, and the third from 1969 to the end of observation period. Four strains from Kuwait and three from Ghana isolated in 1969 and 1970 showed an antigenic structure identical to that of the strains predominant in Uganda in these years. Some strains proved to be of vaccine origin. Twenty-nine type 1 and 24 type 2 strains showed a great variety of characteristics when studied in d, od, and rct/40 marker tests. There was no indication that the distribution of strains according to their in vitro markers would have been different in epidemic and non-epidemic years, or that any particular combination of markers would have been more common among strains isolated from paralytic patients than among those from non-paralytic patients. Nine of 12 type 3 strains had the rct/40(+) marker.", "contents": "Some characteristics of poliovirus strains isolated in Uganda between 1966 and 1971. Sixty-five poliovirus strains were investigated in genetic marker tests in order to obtain information on the characteristics of polioviruses circulating in Uganda where, owing to the insufficient use of live poliovirus vaccine, poliomyelitis remained a serious public health problem. Of the type 1 strains predominant in both epidemic and non-epidemic years, 29 were studied for their antigenic fine structure. Based on their intratypic character, these strains proved to represent six different antigenic variants. Three of these variants were predominant during certain periods; the first variant was present in 1966 and 1968, the second in 1967, and the third from 1969 to the end of observation period. Four strains from Kuwait and three from Ghana isolated in 1969 and 1970 showed an antigenic structure identical to that of the strains predominant in Uganda in these years. Some strains proved to be of vaccine origin. Twenty-nine type 1 and 24 type 2 strains showed a great variety of characteristics when studied in d, od, and rct/40 marker tests. There was no indication that the distribution of strains according to their in vitro markers would have been different in epidemic and non-epidemic years, or that any particular combination of markers would have been more common among strains isolated from paralytic patients than among those from non-paralytic patients. Nine of 12 type 3 strains had the rct/40(+) marker."}
{"id": "PMID:186209", "title": "Monkeypox and whitepox viruses in West and Central Africa.", "content": "Prospects for the eradication of smallpox are now highly encouraging. With the cessation of man-to-man transmission, the question of possible animal reservoirs of smallpox becomes increasingly important. During the period 1970-1975, 20 cases of a smallpox-like disease were detected in smallpox-free areas of tropical rain forest in West and Central Africa. Epidemiological and virological investigations revealed that the disease was caused by an animal poxvirus termed monkeypox virus, a member of the orthopox virus group. The disease spread with difficulty even among susceptible close contacts and does not appear to be sufficiently transmissible to permit continuing infection to become established in man. During the investigations, four orthopox viruses termed whitepox viruses were isolated from rodents and monkeys. The isolates were not distinguishable from variola virus with currently available laboratory techniques, but there is no evidence so far that viruses of this group have infected man. Although there is now substantial and accumulating evidence that there is no animal reservoir for smallpox, continued surveillance and studies in West and Central Africa are warranted.", "contents": "Monkeypox and whitepox viruses in West and Central Africa. Prospects for the eradication of smallpox are now highly encouraging. With the cessation of man-to-man transmission, the question of possible animal reservoirs of smallpox becomes increasingly important. During the period 1970-1975, 20 cases of a smallpox-like disease were detected in smallpox-free areas of tropical rain forest in West and Central Africa. Epidemiological and virological investigations revealed that the disease was caused by an animal poxvirus termed monkeypox virus, a member of the orthopox virus group. The disease spread with difficulty even among susceptible close contacts and does not appear to be sufficiently transmissible to permit continuing infection to become established in man. During the investigations, four orthopox viruses termed whitepox viruses were isolated from rodents and monkeys. The isolates were not distinguishable from variola virus with currently available laboratory techniques, but there is no evidence so far that viruses of this group have infected man. Although there is now substantial and accumulating evidence that there is no animal reservoir for smallpox, continued surveillance and studies in West and Central Africa are warranted."}
{"id": "PMID:186206", "title": "[Anatomo-pathologic aspects of phycomycoses. 6 clinical cases observed in Ivory Coast].", "content": "Six cases of superficial phycomycosis have been recently demonstrated in Ivory Coast, the total number of cases being therefore 8 in this country. After a brief review of the etiology, clinical studies, treatment, and geographical distribution of the 150 world cases known to-day, the author studies the histological lesions of this hypodermic granulatous inflammation, whose characteristic aspects (polynuclear micro-abcesses, palissade histiocytes, filaments sheathed in an eosinophil precipitate) are easy to recognise. These anatomopathological aspects vary according to the topography, clinical evolution and treatment. The author presents a summary of the only ultrastructure known today. He points out the significance of this anatomo-pathologic study, which shows the evolution of the immunitary reaction and permits a relatively precise pronostic.", "contents": "[Anatomo-pathologic aspects of phycomycoses. 6 clinical cases observed in Ivory Coast]. Six cases of superficial phycomycosis have been recently demonstrated in Ivory Coast, the total number of cases being therefore 8 in this country. After a brief review of the etiology, clinical studies, treatment, and geographical distribution of the 150 world cases known to-day, the author studies the histological lesions of this hypodermic granulatous inflammation, whose characteristic aspects (polynuclear micro-abcesses, palissade histiocytes, filaments sheathed in an eosinophil precipitate) are easy to recognise. These anatomopathological aspects vary according to the topography, clinical evolution and treatment. The author presents a summary of the only ultrastructure known today. He points out the significance of this anatomo-pathologic study, which shows the evolution of the immunitary reaction and permits a relatively precise pronostic."}
{"id": "PMID:186210", "title": "Monkeypox-specific antibodies in human and simian sera from the Ivory Coast and Nigeria.", "content": "A test for monkeypox-specific antibodies is described. Monkeypox immune sera can be made type-specific by immunoabsorption with heterotypic poxvirus extracts. Monkeypox-specific antibodies were demonstrated in sera from 9 cynomolgus monkeys (Macaca fascicularis) that had previously been experimentally infected with monkeypox. Monkeypox-specific antibodies were found in 3 wild-caught African monkeys (Cercopithecus spp.) and in 3 human sera collected from Africans in the Ivory Coast and Nigeria 3(1/2)-4 years after they had suffered a pox-like infection. Monkeypox had been recognized in one of the patients by virus isolation, and had been suspected in the others for epidemiological reasons. Vaccinia-specific antibodies were found in 4 human sera collected 6 weeks after smallpox vaccination.The serological results provide the first laboratory evidence of a monkeypox reservoir in wild monkeys.", "contents": "Monkeypox-specific antibodies in human and simian sera from the Ivory Coast and Nigeria. A test for monkeypox-specific antibodies is described. Monkeypox immune sera can be made type-specific by immunoabsorption with heterotypic poxvirus extracts. Monkeypox-specific antibodies were demonstrated in sera from 9 cynomolgus monkeys (Macaca fascicularis) that had previously been experimentally infected with monkeypox. Monkeypox-specific antibodies were found in 3 wild-caught African monkeys (Cercopithecus spp.) and in 3 human sera collected from Africans in the Ivory Coast and Nigeria 3(1/2)-4 years after they had suffered a pox-like infection. Monkeypox had been recognized in one of the patients by virus isolation, and had been suspected in the others for epidemiological reasons. Vaccinia-specific antibodies were found in 4 human sera collected 6 weeks after smallpox vaccination.The serological results provide the first laboratory evidence of a monkeypox reservoir in wild monkeys."}
{"id": "PMID:186211", "title": "[Control of the regeneration of small pieces of the planarian Dugesia tigrina by cylic AMP and GMP nucleotides].", "content": "The effects on regeneration of cyclic nucleotides AMP and GMP were studied on small pieces of the planarian worm Dugesia tigrina. db cAMP, 8Br cGMP and substances acting on their metabolism were used in this work (aminophylline, insulin, imidazole). It seems that these second messengers play a role in a mechanism of regulation in which cGMP has a promotive action and cAMP an inhibitive one.", "contents": "[Control of the regeneration of small pieces of the planarian Dugesia tigrina by cylic AMP and GMP nucleotides]. The effects on regeneration of cyclic nucleotides AMP and GMP were studied on small pieces of the planarian worm Dugesia tigrina. db cAMP, 8Br cGMP and substances acting on their metabolism were used in this work (aminophylline, insulin, imidazole). It seems that these second messengers play a role in a mechanism of regulation in which cGMP has a promotive action and cAMP an inhibitive one."}
{"id": "PMID:186212", "title": "[Electron microscopic observation of the infectious cycle of Visna virus in sheep choroid plexus cells at temperatures under 37 degrees C].", "content": "Electron microscope study of viral penetration at 4 degrees C shows that viral particles first attach to cells. The attachment sites are invaginations which later fuse to form phagocytic cytoplasmic vacuoles. Some virus particles with altered envelopes can be seen in the cytoplasm. After ten days of incubation at 29 degrees C, filamentous inclusions and mature viral particles are seen in the cytoplasm. The cellular membrane budding process and virus release observed at 37 degrees C have disappeared. When the above preparations are warmed to 37 degrees C, budding is seen, and two kinds of extracellular particles are present, one with a clear center and the other with a dense core (mature virus).", "contents": "[Electron microscopic observation of the infectious cycle of Visna virus in sheep choroid plexus cells at temperatures under 37 degrees C]. Electron microscope study of viral penetration at 4 degrees C shows that viral particles first attach to cells. The attachment sites are invaginations which later fuse to form phagocytic cytoplasmic vacuoles. Some virus particles with altered envelopes can be seen in the cytoplasm. After ten days of incubation at 29 degrees C, filamentous inclusions and mature viral particles are seen in the cytoplasm. The cellular membrane budding process and virus release observed at 37 degrees C have disappeared. When the above preparations are warmed to 37 degrees C, budding is seen, and two kinds of extracellular particles are present, one with a clear center and the other with a dense core (mature virus)."}
{"id": "PMID:186213", "title": "[Immunocytochemical evidence for the binding of insulin to the somatotrophic cells of the human hypophysis].", "content": "An immunocytochemical method has demonstrated a hypophyseal cell surface fixation of molecules exhibiting immunological properties of insulin. This fixation occurs massively on GH-cells and on a minority of ACTH cells of the human antehypophysis.", "contents": "[Immunocytochemical evidence for the binding of insulin to the somatotrophic cells of the human hypophysis]. An immunocytochemical method has demonstrated a hypophyseal cell surface fixation of molecules exhibiting immunological properties of insulin. This fixation occurs massively on GH-cells and on a minority of ACTH cells of the human antehypophysis."}
{"id": "PMID:186214", "title": "[Statistical relationship between \"slow-wave sleep\" and \"paradoxical sleep\" in rats].", "content": "In the Rat, statistical analysis of slow sleep (SS) and paradoxical sleep (PS) episodes disclosed two significant (p less than 0,01) positive correlations: (1) Over a four-hour period, the mean duration of PS episodes was correlated to the mean of the just preceding \"light\" SS episodes; (2) On the contrary, from cycle to cycle of sleep-wakefulness, the duration of each PS episode was correlated to that of the \"light\" SS episode of the next cycle.", "contents": "[Statistical relationship between \"slow-wave sleep\" and \"paradoxical sleep\" in rats]. In the Rat, statistical analysis of slow sleep (SS) and paradoxical sleep (PS) episodes disclosed two significant (p less than 0,01) positive correlations: (1) Over a four-hour period, the mean duration of PS episodes was correlated to the mean of the just preceding \"light\" SS episodes; (2) On the contrary, from cycle to cycle of sleep-wakefulness, the duration of each PS episode was correlated to that of the \"light\" SS episode of the next cycle."}
{"id": "PMID:186215", "title": "[Cytoimmunological study of the corticotrophic and corticomelanotrophic cells in the adenohypophysis of Boops salpa L. (marine teleost) in different experimental conditions (variation of salinity and of background color)].", "content": "The cytoimmunological study of the adenohypophysis of Boops salpa (marine Teleost), in different experimental conditions confirmed that the MacConaill's hematoxyline-positive cells contain: 1. ACTH (Corticotrophic Hormone) in the pars distalis, 2. MSH (Melanocyte-Stimulating Hormone) and ACTH in the pars intermedia.", "contents": "[Cytoimmunological study of the corticotrophic and corticomelanotrophic cells in the adenohypophysis of Boops salpa L. (marine teleost) in different experimental conditions (variation of salinity and of background color)]. The cytoimmunological study of the adenohypophysis of Boops salpa (marine Teleost), in different experimental conditions confirmed that the MacConaill's hematoxyline-positive cells contain: 1. ACTH (Corticotrophic Hormone) in the pars distalis, 2. MSH (Melanocyte-Stimulating Hormone) and ACTH in the pars intermedia."}
{"id": "PMID:186216", "title": "[Pharmacologic properties of the toxins isolated from the sea anemone (Anemonia sulcata)].", "content": "We have shown that if toxin II isolated from Anemonia sulcata is mainly cardiotoxic on Rats it nevertheless displays neurotoxic effects. Furthermore it releases acetylcholine from isolated Guinea Pig ileum.", "contents": "[Pharmacologic properties of the toxins isolated from the sea anemone (Anemonia sulcata)]. We have shown that if toxin II isolated from Anemonia sulcata is mainly cardiotoxic on Rats it nevertheless displays neurotoxic effects. Furthermore it releases acetylcholine from isolated Guinea Pig ileum."}
{"id": "PMID:186217", "title": "Detection of perioperative myocardial damage after coronary artery bypass graft surgery.", "content": "In order to evaluate methods for detecting peri-operative myocardial damage we studied 41 patients before and serially following coronary artery bypass graft surgery utilizing the 12-lead ECG, serum MB-CPK measurements, and 99mTc pyrophosphate myocardial scans. Six of the 41 patients (15%) developed persistent new Q waves after surgery. Six other patients demonstrated ischemic ST-T wave changes that persisted for 48 hours or more. Mean total MB-CPK released was highest for the group with new Q waves [1598+/-545 (SE) I.U./L-hr] as compared to the group with ischemic ST-T wave changes 708+/-65 I.U./L-hr) or the group with no ECG changes (262+/-47 I.U./L-hr). Ten patients (24%) has positive postoperative pyrophosphate scans consistent with myocardial infarction. The three techniques were compared in these 41 patients utilizing 465 I.U./L.-hr as the upper limit of normal MB-CPK released after uncomplicated coronary bypass surgery (no ECG changes, negative scan). Five patients with ischemic ECG changes had a positive scan and high MB-CPK; six patients with no ECG changes had high MB-CPK but a negative scan; and one patient with high MB-CPK and new Q wave had a negative scan. We conclude 1) new Q waves on ECG underestimate the incidence of myocardial damage after coronary artery surgery; 2) MB-CPK alone overestimates the incidence of infarction; and 3) a combination of the three techniques is the best means for detecting myocardial damage after coronary artery bypass graft surgery.", "contents": "Detection of perioperative myocardial damage after coronary artery bypass graft surgery. In order to evaluate methods for detecting peri-operative myocardial damage we studied 41 patients before and serially following coronary artery bypass graft surgery utilizing the 12-lead ECG, serum MB-CPK measurements, and 99mTc pyrophosphate myocardial scans. Six of the 41 patients (15%) developed persistent new Q waves after surgery. Six other patients demonstrated ischemic ST-T wave changes that persisted for 48 hours or more. Mean total MB-CPK released was highest for the group with new Q waves [1598+/-545 (SE) I.U./L-hr] as compared to the group with ischemic ST-T wave changes 708+/-65 I.U./L-hr) or the group with no ECG changes (262+/-47 I.U./L-hr). Ten patients (24%) has positive postoperative pyrophosphate scans consistent with myocardial infarction. The three techniques were compared in these 41 patients utilizing 465 I.U./L.-hr as the upper limit of normal MB-CPK released after uncomplicated coronary bypass surgery (no ECG changes, negative scan). Five patients with ischemic ECG changes had a positive scan and high MB-CPK; six patients with no ECG changes had high MB-CPK but a negative scan; and one patient with high MB-CPK and new Q wave had a negative scan. We conclude 1) new Q waves on ECG underestimate the incidence of myocardial damage after coronary artery surgery; 2) MB-CPK alone overestimates the incidence of infarction; and 3) a combination of the three techniques is the best means for detecting myocardial damage after coronary artery bypass graft surgery."}
{"id": "PMID:186218", "title": "The characterization of the ACTH produced by a primary pituitary tumour in a patient with Cushing's disease.", "content": "The nature of ACTH present in pituitary tumours associated with Cushing's disease has not been previously characterized nor correlated with the electron microscopic appearance. The present report describes the culture of tumour tissue obtained from a patient with a pituitary tumour associated with Cushing's disease, and the characterization of the ACTH content of tumour and media by bioassay, immunoassay, and Sephadex G-50 gel filtration. Electron microscopic studies were also performed. The pathological diagnosis was pituitary adenoma with basophilic PAS-positive granules. Electron microscopy showed uniformity of size and shape of the tumour cells, the presence of secretory granules of varying size and density, and disorganized tubular and vacuolar arrays of endoplasmic reticulum. The bioreactive ACTH content of the tumour was 0-29 mug/g, which is markedly below that seen in the normal pituitary, but within the range reported for ectopic ACTH-producing tumours. Immunoreactive ACTH when measured by a C-terminal antibody was five-fold higher than when measured by an N-terminal antibody; the latter gave a value of 1-24 mjg/g. On Sephadex G-50 gel filtration, 9% of the N-terminal immunoreactivity was present in the Vo fraction ('big' ACTH). This latter fraction had a greater percentage of bioreactivity (28%) than previously reported for this molecular species. Analysis of the tumour culture medium revealed a variation in molecular size similar to that seen in the tumour, although the percentage of ACTH of large molecular size was greater, suggesting increased secretion of a possible 'prohormone' by the tumour. Plasma ACTH was characterized by a 2:1 ratio of immunoreactivity (N-terminal) to bioreactivity, and a 4:1 ratio of C-terminal/N-terminal immunoreactivity. This report also appears to be the first of successful short-term tissue culture of a primary ACTH-producing tumour. The granule size was considerably larger than that reported for normal pituitary ACTH-containing cells.", "contents": "The characterization of the ACTH produced by a primary pituitary tumour in a patient with Cushing's disease. The nature of ACTH present in pituitary tumours associated with Cushing's disease has not been previously characterized nor correlated with the electron microscopic appearance. The present report describes the culture of tumour tissue obtained from a patient with a pituitary tumour associated with Cushing's disease, and the characterization of the ACTH content of tumour and media by bioassay, immunoassay, and Sephadex G-50 gel filtration. Electron microscopic studies were also performed. The pathological diagnosis was pituitary adenoma with basophilic PAS-positive granules. Electron microscopy showed uniformity of size and shape of the tumour cells, the presence of secretory granules of varying size and density, and disorganized tubular and vacuolar arrays of endoplasmic reticulum. The bioreactive ACTH content of the tumour was 0-29 mug/g, which is markedly below that seen in the normal pituitary, but within the range reported for ectopic ACTH-producing tumours. Immunoreactive ACTH when measured by a C-terminal antibody was five-fold higher than when measured by an N-terminal antibody; the latter gave a value of 1-24 mjg/g. On Sephadex G-50 gel filtration, 9% of the N-terminal immunoreactivity was present in the Vo fraction ('big' ACTH). This latter fraction had a greater percentage of bioreactivity (28%) than previously reported for this molecular species. Analysis of the tumour culture medium revealed a variation in molecular size similar to that seen in the tumour, although the percentage of ACTH of large molecular size was greater, suggesting increased secretion of a possible 'prohormone' by the tumour. Plasma ACTH was characterized by a 2:1 ratio of immunoreactivity (N-terminal) to bioreactivity, and a 4:1 ratio of C-terminal/N-terminal immunoreactivity. This report also appears to be the first of successful short-term tissue culture of a primary ACTH-producing tumour. The granule size was considerably larger than that reported for normal pituitary ACTH-containing cells."}
{"id": "PMID:186219", "title": "Hormonal variations in secondary amenorrhoea during the metyrapone test.", "content": "The occurrence of uterine bleeding following administration of Metyrapone in cases of secondary amenorrhoea and oligomenorrhoea led the authors to measure pituitary, gonadal and adrenal hormone levels, before and after the oral administration of this drug in sixteen patients, in an attempt to provide an interpretation of this phenomenon. There were expected changes in plasma ACTH and urinary 17-hydroxycorticosteroids, but no variations were noted in serum FSH and LH, plasma oestradiol and urinary oestrogens; the most important alterations occurred in plasma progesterone and urinary pregnanetriol levels. It is suggested that bleeding occurs because of the changes which are induced in plasma progesterone levels.", "contents": "Hormonal variations in secondary amenorrhoea during the metyrapone test. The occurrence of uterine bleeding following administration of Metyrapone in cases of secondary amenorrhoea and oligomenorrhoea led the authors to measure pituitary, gonadal and adrenal hormone levels, before and after the oral administration of this drug in sixteen patients, in an attempt to provide an interpretation of this phenomenon. There were expected changes in plasma ACTH and urinary 17-hydroxycorticosteroids, but no variations were noted in serum FSH and LH, plasma oestradiol and urinary oestrogens; the most important alterations occurred in plasma progesterone and urinary pregnanetriol levels. It is suggested that bleeding occurs because of the changes which are induced in plasma progesterone levels."}
{"id": "PMID:186220", "title": "1-Alpha-hydroxycholecalciferol in the treatment of hypocalcaemic psychosis.", "content": "Two patients with profound hypocalcaemia due to uraemia and hypoparathyroidism respectively presented with alterations of mental state as their dominant symptom. 1-Alpha-hydroxycholecalciferol (1-alpha-OHD3) was chosen as the principal therapy because of its potency and rapid action. In both patients the plasma calcium was restored towards normal and the symptoms relieved within a very short period. The cases illustrate the role of 1-alpha-OHD3 in severe hypocalcaemia due to two different causes and provide experience on which to base treatment regimes for future patients similarly afflicted.", "contents": "1-Alpha-hydroxycholecalciferol in the treatment of hypocalcaemic psychosis. Two patients with profound hypocalcaemia due to uraemia and hypoparathyroidism respectively presented with alterations of mental state as their dominant symptom. 1-Alpha-hydroxycholecalciferol (1-alpha-OHD3) was chosen as the principal therapy because of its potency and rapid action. In both patients the plasma calcium was restored towards normal and the symptoms relieved within a very short period. The cases illustrate the role of 1-alpha-OHD3 in severe hypocalcaemia due to two different causes and provide experience on which to base treatment regimes for future patients similarly afflicted."}
{"id": "PMID:186221", "title": "The effect of electric convulsion therapy on the circulating concentrations of pituitary hormones, cortisol and cyclic adenosine monophosphate.", "content": "In order to evaluate the effect of electroconvulsive therapy on the human pituitary-adrenal function, serial plasma samples were assayed for FSH, LH, TSH, HGH, ACTH, cortisol and cyclic AMP before and after nine shocks in five subjects. A prominent finding was the rapid stimulation of the ACTH-cortisol production in all subjects, while no consistent changes in FSH, LH, TSH, HGH or cyclic AMP were found.", "contents": "The effect of electric convulsion therapy on the circulating concentrations of pituitary hormones, cortisol and cyclic adenosine monophosphate. In order to evaluate the effect of electroconvulsive therapy on the human pituitary-adrenal function, serial plasma samples were assayed for FSH, LH, TSH, HGH, ACTH, cortisol and cyclic AMP before and after nine shocks in five subjects. A prominent finding was the rapid stimulation of the ACTH-cortisol production in all subjects, while no consistent changes in FSH, LH, TSH, HGH or cyclic AMP were found."}
{"id": "PMID:186222", "title": "Antibody-dependent cellular cytotoxicity (ADCC) against Epstein-Barr virus-determined membrane antigens. I. Reactivity in sera from normal persons and from patients with acute infectious mononucleosis.", "content": "The capacity of antibodies, directed against EBV-determined membrane antigens (MA), to induce antibody-dependent cellular cytotoxicity (ADCC) against EBV superinfected lymphoid cell lines was investigated. Such reactive antibodies were found, at high dilutions, in sera from normal EBV-positive persons but not in sera from EBV-negative persons. Sera from patients with acute infectious mononucleosis (IM), which develop EBV-specific killer T cells, did not induce ADCC. The difference in specificity between ADCC and EBV-specific killer T cells is briefly discussed.", "contents": "Antibody-dependent cellular cytotoxicity (ADCC) against Epstein-Barr virus-determined membrane antigens. I. Reactivity in sera from normal persons and from patients with acute infectious mononucleosis. The capacity of antibodies, directed against EBV-determined membrane antigens (MA), to induce antibody-dependent cellular cytotoxicity (ADCC) against EBV superinfected lymphoid cell lines was investigated. Such reactive antibodies were found, at high dilutions, in sera from normal EBV-positive persons but not in sera from EBV-negative persons. Sera from patients with acute infectious mononucleosis (IM), which develop EBV-specific killer T cells, did not induce ADCC. The difference in specificity between ADCC and EBV-specific killer T cells is briefly discussed."}
{"id": "PMID:186223", "title": "Dose-related sleep disturbances induced by coffee and caffeine.", "content": "In a 13-night sleep laboratory study, each of 18 normal young adult males twice received 1 cup of warm water, 1-, 2-, and 4-cup equivalents of regular coffee, a 4-cup equivalent of decaffeinated coffee, and a 4-cup equivalent of caffeine. All beverages were administered 30 min before bedtime according to a balanced Latin-square design. Regular coffee produced dose-related changes in most standard electroencephalogram-electrooculogram (EEG-EOG) sleep parameters, and the 4-cup equivalents of regular coffee and caffeine produced equivalent effects. Decaffeinated coffee had no effect. Regular coffee and caffeine caused rapid eye movement (REM) sleep to shift to the early part of the night and stages 3 and 4 sleep to shift to the later part. Coffee also produced dose-related changes in several subjects estimates of sleep characteristics. These results suggest that coffee and caffeine may be used in normal subjects to induce symptoms mimicking those of insomnia. Such a tool should promote further understanding of insomnia.", "contents": "Dose-related sleep disturbances induced by coffee and caffeine. In a 13-night sleep laboratory study, each of 18 normal young adult males twice received 1 cup of warm water, 1-, 2-, and 4-cup equivalents of regular coffee, a 4-cup equivalent of decaffeinated coffee, and a 4-cup equivalent of caffeine. All beverages were administered 30 min before bedtime according to a balanced Latin-square design. Regular coffee produced dose-related changes in most standard electroencephalogram-electrooculogram (EEG-EOG) sleep parameters, and the 4-cup equivalents of regular coffee and caffeine produced equivalent effects. Decaffeinated coffee had no effect. Regular coffee and caffeine caused rapid eye movement (REM) sleep to shift to the early part of the night and stages 3 and 4 sleep to shift to the later part. Coffee also produced dose-related changes in several subjects estimates of sleep characteristics. These results suggest that coffee and caffeine may be used in normal subjects to induce symptoms mimicking those of insomnia. Such a tool should promote further understanding of insomnia."}
{"id": "PMID:186224", "title": "Probucol: a new cholesterol-lowering drug effective in patients with type II hyperlipoproteinemia.", "content": "Type II hyperlipoproteinemia or hyperbetalipoproteinemia (B-HLP), a condition with considerable atherogenic potential, is one of the most difficult lipid disorders requiring treatment. Since this abnormality responds minimally to dietary therapy alone, supplemental drug therapy is usually essential. Although the available bile-sequestering resins are effective in B-HLP, these substances are unpalatable and constipating. Since lifelong drug therapy is necessary as an adjunct to diet in the treatment of B-HLP, the ideal drug should be both effective and well tolerated. Probucol, a new cholesterol-lowering drug in tablet form without serious adverse effects, was evaluated in a 12-wk double-blind crossover trial in 11 patients with B-HLP whose serum cholesterol levels were in excess of 275 mg/dl. Probucol, in a dosage of 500 mg twice daily, produced a 10% or greater reduction in serum cholesterol levels in all 11 patients. Serum cholesterol was lowered (p less than 0.01) from 353 to 291 mg/dl in the entire group receiving probucol. There was no significant change (p greater than 0.1) in serum cholesterol (352 mg/dl) during placebo administration. These were no untoward drug effects during the study, and all patients maintained excellent complicance to the schedule of medication. These results indicate that probucol possesses considerable cholesterol-lowering activity and may be a promising new nontoxic therapeutic agent in type II hyperlipoproteinemia.", "contents": "Probucol: a new cholesterol-lowering drug effective in patients with type II hyperlipoproteinemia. Type II hyperlipoproteinemia or hyperbetalipoproteinemia (B-HLP), a condition with considerable atherogenic potential, is one of the most difficult lipid disorders requiring treatment. Since this abnormality responds minimally to dietary therapy alone, supplemental drug therapy is usually essential. Although the available bile-sequestering resins are effective in B-HLP, these substances are unpalatable and constipating. Since lifelong drug therapy is necessary as an adjunct to diet in the treatment of B-HLP, the ideal drug should be both effective and well tolerated. Probucol, a new cholesterol-lowering drug in tablet form without serious adverse effects, was evaluated in a 12-wk double-blind crossover trial in 11 patients with B-HLP whose serum cholesterol levels were in excess of 275 mg/dl. Probucol, in a dosage of 500 mg twice daily, produced a 10% or greater reduction in serum cholesterol levels in all 11 patients. Serum cholesterol was lowered (p less than 0.01) from 353 to 291 mg/dl in the entire group receiving probucol. There was no significant change (p greater than 0.1) in serum cholesterol (352 mg/dl) during placebo administration. These were no untoward drug effects during the study, and all patients maintained excellent complicance to the schedule of medication. These results indicate that probucol possesses considerable cholesterol-lowering activity and may be a promising new nontoxic therapeutic agent in type II hyperlipoproteinemia."}
{"id": "PMID:186225", "title": "The influence of orthophosphate on the renal handling of inorganic pyrophosphate in man and dog.", "content": "1. The urinary excretion of inorganic pyrophosphate (PPi), a known inhibitor of the growth and aggregation of crystals of calcium phosphate and calcium oxalate, increases after ingestion of orthophosphate (Pi). This effect may contribute to the apparent ability of oral phosphate to reduce the formation of urinary stones in man. This paper is a study of the mechanism by which Pi increases PPi excretion, investigated by renal clearance techniques in man and renal arterial infusion in dogs. PPi in plasma was measured by an isotope-dilution method after ion-exchange chromatography. 2. The mean renal clearance of endogenous PPi in ten men was 7-9 +/- 1-7 (SE) ml/min, and the mean ratio of PPi clearance to creatinine clearance was 0-08 +/- 0-02 (SE). The oral ingestion of Pi increased the urinary excretion and renal clearance of PPi about threefold, without significantly changing its concentration in plasma. 3. In dogs, the infusion of Pi into one renal artery caused a greater increase in urinary PPi from the infused than from the non-infused kidney, an effect that could be accentuated by simultaneous intravenous infusion of PPi. In dogs, only 1-3% of an injected or infused dose of PPi appeared intact in the urine, regardless of whether it was infused into the systemic or renal circulation. 4. These results suggest that Pi has a direct affect on the kidney to increase the excretion of PPi. It is possible that Pi either interferes with tubular reabsorption of PPi, perhaps by competing for a common tubular transport mechanism, or that Pi diminishes the intrarenal hydrolysis of PPi.", "contents": "The influence of orthophosphate on the renal handling of inorganic pyrophosphate in man and dog. 1. The urinary excretion of inorganic pyrophosphate (PPi), a known inhibitor of the growth and aggregation of crystals of calcium phosphate and calcium oxalate, increases after ingestion of orthophosphate (Pi). This effect may contribute to the apparent ability of oral phosphate to reduce the formation of urinary stones in man. This paper is a study of the mechanism by which Pi increases PPi excretion, investigated by renal clearance techniques in man and renal arterial infusion in dogs. PPi in plasma was measured by an isotope-dilution method after ion-exchange chromatography. 2. The mean renal clearance of endogenous PPi in ten men was 7-9 +/- 1-7 (SE) ml/min, and the mean ratio of PPi clearance to creatinine clearance was 0-08 +/- 0-02 (SE). The oral ingestion of Pi increased the urinary excretion and renal clearance of PPi about threefold, without significantly changing its concentration in plasma. 3. In dogs, the infusion of Pi into one renal artery caused a greater increase in urinary PPi from the infused than from the non-infused kidney, an effect that could be accentuated by simultaneous intravenous infusion of PPi. In dogs, only 1-3% of an injected or infused dose of PPi appeared intact in the urine, regardless of whether it was infused into the systemic or renal circulation. 4. These results suggest that Pi has a direct affect on the kidney to increase the excretion of PPi. It is possible that Pi either interferes with tubular reabsorption of PPi, perhaps by competing for a common tubular transport mechanism, or that Pi diminishes the intrarenal hydrolysis of PPi."}
{"id": "PMID:186226", "title": "Regulation of the human pyruvate dehydrogenase complex.", "content": "1. The pyruvate dehydrogenase complex from human heart has been partially purified and shown to be regulated by a phosphorylation-dephosphorylation cycle similar to that previously found for other mammalian tissues. 2. Incubation of the complex with ATP (2 mmol/1) led to its inactivation associated with the concomitant incorporation into the protein of 32P from the terminal phosphate group of the ATP. Pyruvate, ADP, thiamin pyrophosphate and dichloroacetate diminished the rate of inactivation by ATP. 3. Pyruvate dehydrogenase phosphatase from human heart requires Mg2+  for activity and is sensitive to Ca2+ at concentrations of a few mumol/1. Similar ionic requirements of the skeletal muscle phosphatase have been demonstrated in a crude tissue extract. 4. The activity of pyruvate dehydrogenase in human adipose tissue was less than 10% of typical values in rats. This could be due to the high level of dietary fat consumed by humans, which is known to repress the enzyme activity in rats.", "contents": "Regulation of the human pyruvate dehydrogenase complex. 1. The pyruvate dehydrogenase complex from human heart has been partially purified and shown to be regulated by a phosphorylation-dephosphorylation cycle similar to that previously found for other mammalian tissues. 2. Incubation of the complex with ATP (2 mmol/1) led to its inactivation associated with the concomitant incorporation into the protein of 32P from the terminal phosphate group of the ATP. Pyruvate, ADP, thiamin pyrophosphate and dichloroacetate diminished the rate of inactivation by ATP. 3. Pyruvate dehydrogenase phosphatase from human heart requires Mg2+  for activity and is sensitive to Ca2+ at concentrations of a few mumol/1. Similar ionic requirements of the skeletal muscle phosphatase have been demonstrated in a crude tissue extract. 4. The activity of pyruvate dehydrogenase in human adipose tissue was less than 10% of typical values in rats. This could be due to the high level of dietary fat consumed by humans, which is known to repress the enzyme activity in rats."}
{"id": "PMID:186227", "title": "The metabolism in vivo and in vitro of plasma low-density lipoprotein from a subject with inherited hypercholesterolaemia.", "content": "1. The metabolism in vivo and in vitro of an abnormal low-density lipoprotein (LDL) obtained from a patient with an inherited form of hypercholesterolaemia was compared with that of LDL obtained from a normal subject. 2. The rates of turnover of the apoprotein of the two types of LDL in a normal subject, and their uptake and catabolism by normal lymphocytes in vitro, were similar. 3. It is concluded that the abnormal behaviour of the patient's LDL may not be due to an abnormality in the apoprotein component.", "contents": "The metabolism in vivo and in vitro of plasma low-density lipoprotein from a subject with inherited hypercholesterolaemia. 1. The metabolism in vivo and in vitro of an abnormal low-density lipoprotein (LDL) obtained from a patient with an inherited form of hypercholesterolaemia was compared with that of LDL obtained from a normal subject. 2. The rates of turnover of the apoprotein of the two types of LDL in a normal subject, and their uptake and catabolism by normal lymphocytes in vitro, were similar. 3. It is concluded that the abnormal behaviour of the patient's LDL may not be due to an abnormality in the apoprotein component."}
{"id": "PMID:186228", "title": "Inverse relationship in Jamaica between plasma high-density lipoprotein cholesterol concentration and coronary-disease risk as predicted by multiple risk-factor status.", "content": "1. The relation between plasma high-density lipoprotein (HDL) cholesterol concentration and multiple coronary-risk factor status has been assessed in fifty-two middle-aged clinically healthy men from urban and rural Jamaica. 2. Rural hill-farmers had a superior exercise performance (assessed by the responses to submaximal test exercise), less body fat, and lower fasting levels for plasma total cholesterol, low-density liproprotein (LDL) cholesterol, total triglyceride and blood glucose than urban businessmen. Mean plasma HDL cholesterol was considerably higher in farmers then businessmen. 3. Multilinear regression analysis showed HDL cholesterol concentration to be independently and inversely correlated with plasma triglyceride, LDL cholesterol and diastolic blood pressure and that these relationships applied across the urban and rural sub-groups. There was also some evidence that HDL cholesterol concentration increased with stature. When these factors were taken into account, age, ethnic group, adiposity, weight, exercise performance, smoking history and blood glucose made no further significant contribution to the prediction of HDL cholesterol concentration. 4. Thus plasma HDL cholesterol concentration was highest in those subjects with the lowest coronary-risk as predicted by their multiple risk-factor status, an observation which supported other evidence that coronary-risk is inversely related to plasma HDL concentration. 5. The results raise the possibility that coronary-risk can be more simply estimated from the plasma HDL cholesterol concentration than from a consideration of other major lipid risk factors and blood pressure.", "contents": "Inverse relationship in Jamaica between plasma high-density lipoprotein cholesterol concentration and coronary-disease risk as predicted by multiple risk-factor status. 1. The relation between plasma high-density lipoprotein (HDL) cholesterol concentration and multiple coronary-risk factor status has been assessed in fifty-two middle-aged clinically healthy men from urban and rural Jamaica. 2. Rural hill-farmers had a superior exercise performance (assessed by the responses to submaximal test exercise), less body fat, and lower fasting levels for plasma total cholesterol, low-density liproprotein (LDL) cholesterol, total triglyceride and blood glucose than urban businessmen. Mean plasma HDL cholesterol was considerably higher in farmers then businessmen. 3. Multilinear regression analysis showed HDL cholesterol concentration to be independently and inversely correlated with plasma triglyceride, LDL cholesterol and diastolic blood pressure and that these relationships applied across the urban and rural sub-groups. There was also some evidence that HDL cholesterol concentration increased with stature. When these factors were taken into account, age, ethnic group, adiposity, weight, exercise performance, smoking history and blood glucose made no further significant contribution to the prediction of HDL cholesterol concentration. 4. Thus plasma HDL cholesterol concentration was highest in those subjects with the lowest coronary-risk as predicted by their multiple risk-factor status, an observation which supported other evidence that coronary-risk is inversely related to plasma HDL concentration. 5. The results raise the possibility that coronary-risk can be more simply estimated from the plasma HDL cholesterol concentration than from a consideration of other major lipid risk factors and blood pressure."}
{"id": "PMID:186231", "title": "Effect of some nucleotides on the regulation of glycosaminoglycan biosynthesis.", "content": "The effect of some nucleotides on UDP-glucose dehydrogenase (EC. 1.1.1.22) and UDP-glucose 4'-epimerase (EC 5.1.3.2) extracted from epiphysial-plate cartilage of newborn pigs was investigated. UDP-xylose acts as a co-operative allosteric inhibitor of UDP-glucose dehydrogenase, whereas it does not inhibit UDP-glucose 4'-epimerase activity: the inhibition of UDP-glucose dehydrogenase results in an increase of UDP-galactose synthesis, in agreement with the equilibrium constant of UDP-glucose 4'-epimerase reaction. Because of the presence of UDP-glucose 4'-epimerase activity in the enzyme extract, the addition of UDP-galactose induces an increase in reaction rate of UDP-glucose dehydrogenase. NADH inhibits both UDP-glucose dehydrogenase and UDP-glucose 4'-epimerase activities: in the presence of non-saturating NAD concentrations, NADH acts as a co-operative allosteric inhibitor of both enzymes. The inhibitory effect of NADH seems to be strikingly correlated with the value of NAD/NADH ratio and pH. In any case, the percentage inhibition of UDP-glucose 4'-epimerase, under the same experimental conditions, is always higher than that of UDP-glucose dehydrogenase.", "contents": "Effect of some nucleotides on the regulation of glycosaminoglycan biosynthesis. The effect of some nucleotides on UDP-glucose dehydrogenase (EC. 1.1.1.22) and UDP-glucose 4'-epimerase (EC 5.1.3.2) extracted from epiphysial-plate cartilage of newborn pigs was investigated. UDP-xylose acts as a co-operative allosteric inhibitor of UDP-glucose dehydrogenase, whereas it does not inhibit UDP-glucose 4'-epimerase activity: the inhibition of UDP-glucose dehydrogenase results in an increase of UDP-galactose synthesis, in agreement with the equilibrium constant of UDP-glucose 4'-epimerase reaction. Because of the presence of UDP-glucose 4'-epimerase activity in the enzyme extract, the addition of UDP-galactose induces an increase in reaction rate of UDP-glucose dehydrogenase. NADH inhibits both UDP-glucose dehydrogenase and UDP-glucose 4'-epimerase activities: in the presence of non-saturating NAD concentrations, NADH acts as a co-operative allosteric inhibitor of both enzymes. The inhibitory effect of NADH seems to be strikingly correlated with the value of NAD/NADH ratio and pH. In any case, the percentage inhibition of UDP-glucose 4'-epimerase, under the same experimental conditions, is always higher than that of UDP-glucose dehydrogenase."}
{"id": "PMID:186235", "title": "Regulation of active ion transport in the small intestine.", "content": "The epithelium of the small intestine can both actively absorb and actively secrete electrolytes and water. Secretion can be elicited in vitro by adding cyclic AMP or a stimulator of intestinal mucosal adenylate cyclase (cholera and Escherichia coli enterotoxins, prostaglandins, vasoactive intestinal peptide) or an inhibitor of cyclic AMP phosphodiesterase (theophylline). Cyclic AMP appears to alter intestinal ion transport at two different loci: it inhibits a coupled influx process for Na+ and Cl- at the luminal border, thereby reducing active absorption of NaCl, and it also stimulates the active secretion of anion (or Na+ and anion). A variety of evidence suggests that these two effects of cyclic AMP reside in different types of cells, the former in villus cells and the latter in crypt cells. The latter process is Na+-dependent and is inhibited by low concentrations of ouabain and ethacrynic acid. Active ion absorption in vitro can be enhanced by (1) stimulating Na+-coupled organic solute absorption with glucose, amino acids and possibly also oligo peptides; (2) reducing the HCO3- concentration and/or pH of the serosal bathing solution; and (3) introducing an alpha-adrenergic agonist. Cholera toxin-induced fluid production in vivo can be diminished by the first of these manoeuvres. The in vivo efficacies of the other two have not been evaluated.", "contents": "Regulation of active ion transport in the small intestine. The epithelium of the small intestine can both actively absorb and actively secrete electrolytes and water. Secretion can be elicited in vitro by adding cyclic AMP or a stimulator of intestinal mucosal adenylate cyclase (cholera and Escherichia coli enterotoxins, prostaglandins, vasoactive intestinal peptide) or an inhibitor of cyclic AMP phosphodiesterase (theophylline). Cyclic AMP appears to alter intestinal ion transport at two different loci: it inhibits a coupled influx process for Na+ and Cl- at the luminal border, thereby reducing active absorption of NaCl, and it also stimulates the active secretion of anion (or Na+ and anion). A variety of evidence suggests that these two effects of cyclic AMP reside in different types of cells, the former in villus cells and the latter in crypt cells. The latter process is Na+-dependent and is inhibited by low concentrations of ouabain and ethacrynic acid. Active ion absorption in vitro can be enhanced by (1) stimulating Na+-coupled organic solute absorption with glucose, amino acids and possibly also oligo peptides; (2) reducing the HCO3- concentration and/or pH of the serosal bathing solution; and (3) introducing an alpha-adrenergic agonist. Cholera toxin-induced fluid production in vivo can be diminished by the first of these manoeuvres. The in vivo efficacies of the other two have not been evaluated."}
{"id": "PMID:186236", "title": "The aetiology of diarrhoea in newborn infants.", "content": "Diarrhoea is a common problem in newborn infants in hospital nurseries. In the past, sporadic diarrhoea was often attributed to dietary indiscretion by the mother, and epidemic diarrhoea was though to be caused by an unknown infectious agent. Techniques with which to locate non-cultivable viruses and untypable enteropathogenic strains of Escherichia coli allow reevaluation of the aetiology of diarrhoea in newborn infants. Preliminary results from Melbourne, Australia, suggest that most diarrhoea in newborn infants is induced by a specific infectious agent. During 1975 the agent most often identified from sporadic and epidemic diarrhoea in hospital nurseries was a reovirus-like particle (\"duovirus\"). Enterotoxin-producing strains of E. coli were rarely isolated. Future attempts to protect newborn infants from developing diarrhoea must be based on an accurate understanding of the aetiology of this disease.", "contents": "The aetiology of diarrhoea in newborn infants. Diarrhoea is a common problem in newborn infants in hospital nurseries. In the past, sporadic diarrhoea was often attributed to dietary indiscretion by the mother, and epidemic diarrhoea was though to be caused by an unknown infectious agent. Techniques with which to locate non-cultivable viruses and untypable enteropathogenic strains of Escherichia coli allow reevaluation of the aetiology of diarrhoea in newborn infants. Preliminary results from Melbourne, Australia, suggest that most diarrhoea in newborn infants is induced by a specific infectious agent. During 1975 the agent most often identified from sporadic and epidemic diarrhoea in hospital nurseries was a reovirus-like particle (\"duovirus\"). Enterotoxin-producing strains of E. coli were rarely isolated. Future attempts to protect newborn infants from developing diarrhoea must be based on an accurate understanding of the aetiology of this disease."}
{"id": "PMID:186237", "title": "Implications of recent virological researches.", "content": "Rotaviruses (duoviruses) can be found in more than half the cases of acute diarrhoea in children up to the age of six or seven. About that age almost everyone has antibodies to them. Second infections occur and may not be as rare as laboratory findings so far suggest. Very young infants sometimes get subclinical disease-the effect of maternal antibody transmitted across the placenta? Very similar viruses, all possessing a common antigen detectable by immunofluorescence, are known to infect and/or cause diarrhoea in children, calves, piglets, mice, foals and monkeys. The calf virus and the human virus both infect piglets; piglet virus infects calves; we don't know whether any of these can infect children. Other mammals probably have similar diarrhoea viruses. An antigen common to all these viruses is probably in the inner capsid layer, and \"species-specific\" antigens are probably in the outer capsid layer. A precise test for comparing different strains is bably needed. Adenoviruses possibly cause a smaller proportion of cases of diarrhoea. Coronaviruses, well-known as enteric pathogens of pigs and calves, appear also to infect adults and children. 27 nm particles and 22-23 nm particles of density 1.4 (and other particles) can be found in faeces of children with natural diarrhoea and adults with experimental diarrhoea, sometimes in enormous numbers. It is not yet established whether they cause disease. Rotaviruses, animal coronaviruses and \"Norwalk\" virus attack the disaccharidase-producing epithelium of the small bowel; adenovirus pathology is unknown.A safe attenuated live vaccine strain of the human rotavirus urgently needs to be developed.", "contents": "Implications of recent virological researches. Rotaviruses (duoviruses) can be found in more than half the cases of acute diarrhoea in children up to the age of six or seven. About that age almost everyone has antibodies to them. Second infections occur and may not be as rare as laboratory findings so far suggest. Very young infants sometimes get subclinical disease-the effect of maternal antibody transmitted across the placenta? Very similar viruses, all possessing a common antigen detectable by immunofluorescence, are known to infect and/or cause diarrhoea in children, calves, piglets, mice, foals and monkeys. The calf virus and the human virus both infect piglets; piglet virus infects calves; we don't know whether any of these can infect children. Other mammals probably have similar diarrhoea viruses. An antigen common to all these viruses is probably in the inner capsid layer, and \"species-specific\" antigens are probably in the outer capsid layer. A precise test for comparing different strains is bably needed. Adenoviruses possibly cause a smaller proportion of cases of diarrhoea. Coronaviruses, well-known as enteric pathogens of pigs and calves, appear also to infect adults and children. 27 nm particles and 22-23 nm particles of density 1.4 (and other particles) can be found in faeces of children with natural diarrhoea and adults with experimental diarrhoea, sometimes in enormous numbers. It is not yet established whether they cause disease. Rotaviruses, animal coronaviruses and \"Norwalk\" virus attack the disaccharidase-producing epithelium of the small bowel; adenovirus pathology is unknown.A safe attenuated live vaccine strain of the human rotavirus urgently needs to be developed."}
{"id": "PMID:186238", "title": "Pathogenic rotaviruses isolated from pigs and calves.", "content": "Rotavirus is commonly isolated from diarrhoeic calves and pigs. Bacterium-free faecal filtrates containing rotavirus from five different outbreaks of disease in calves all caused diarrhoea and clinical illness in gnotobiotic calves and five different isolates from pigs were inoculated into gnotobiotic pigs with similar results. The author was unsuccessful in finding an avirulent strain although one of the calf isolates was from a non-diarrhoeic calf. The laboratory strain of calf virus retained its virulence after being passaged seven times in gnotobiotic calves, which included sucrose density gradient purification on two occasions. The calf tissue culture-adapted virus retained its virulence. Rotavirus isolates from humans, calves, pigs and foals were infectious to pigs. Although sharing a common antigen the viruses were separable according to host infectivity, virulence and neutralizing antigens. In both calves and pigs the main lesion was loss of the epithelial cell of the small intestine and stunting of villi. Passive protection of the calf and pig was poor. Circulating antibody was not protective and although high levels of clolostral antibody in the gut lumen at the time of infection protected calves clinically, the antibody level secreted in milk declined 10-fold 48 hours after parturition. Frequently other viruses are found together with rotavirus in cases of diarrhoea. Their role is being investigated.", "contents": "Pathogenic rotaviruses isolated from pigs and calves. Rotavirus is commonly isolated from diarrhoeic calves and pigs. Bacterium-free faecal filtrates containing rotavirus from five different outbreaks of disease in calves all caused diarrhoea and clinical illness in gnotobiotic calves and five different isolates from pigs were inoculated into gnotobiotic pigs with similar results. The author was unsuccessful in finding an avirulent strain although one of the calf isolates was from a non-diarrhoeic calf. The laboratory strain of calf virus retained its virulence after being passaged seven times in gnotobiotic calves, which included sucrose density gradient purification on two occasions. The calf tissue culture-adapted virus retained its virulence. Rotavirus isolates from humans, calves, pigs and foals were infectious to pigs. Although sharing a common antigen the viruses were separable according to host infectivity, virulence and neutralizing antigens. In both calves and pigs the main lesion was loss of the epithelial cell of the small intestine and stunting of villi. Passive protection of the calf and pig was poor. Circulating antibody was not protective and although high levels of clolostral antibody in the gut lumen at the time of infection protected calves clinically, the antibody level secreted in milk declined 10-fold 48 hours after parturition. Frequently other viruses are found together with rotavirus in cases of diarrhoea. Their role is being investigated."}
{"id": "PMID:186239", "title": "Recent advances in the aetiology of viral gastroenteritis.", "content": "Studies with the human reovirus-like (HRVL) agnet, also designated rotavirus and duovirus, have revealed that it is a major aetiological agent of diarrhoea of infants and young children in many parts of the world. In a study of patients admitted with a diarrhoeal illness to the Children's Hospital of the District of Columbia in the United States from January 1974 to June 1975, it was found that half of the patients studied by both virus shedding (by electron microscopy) and serological (complement-fixation) techniques demonstrated evidence of infection with the HRVL agent. The temporal distribution of infections with the HRVL agent followed a seasonal pattern with this agent being shed exclusively by patients admitted during the cooler months of the year. Electron microscopic examination of stools was as efficient as serological methods for detecting infection with the HRVL agent. We also initiated studies to determine the possible mode of transmission of the HRVL agent by studying contacts of hospitalized patients. We found that 35% parents of patients with HRVL infections were also infected with the HRVL agent. Serological studies revealed that the HRVL agent was antigenically related to the Nebraska Calf Diarrhoea Virus, the epizootic diarrhoea of infant mice virus, the SA-11 virus, and the \"O\" agent.", "contents": "Recent advances in the aetiology of viral gastroenteritis. Studies with the human reovirus-like (HRVL) agnet, also designated rotavirus and duovirus, have revealed that it is a major aetiological agent of diarrhoea of infants and young children in many parts of the world. In a study of patients admitted with a diarrhoeal illness to the Children's Hospital of the District of Columbia in the United States from January 1974 to June 1975, it was found that half of the patients studied by both virus shedding (by electron microscopy) and serological (complement-fixation) techniques demonstrated evidence of infection with the HRVL agent. The temporal distribution of infections with the HRVL agent followed a seasonal pattern with this agent being shed exclusively by patients admitted during the cooler months of the year. Electron microscopic examination of stools was as efficient as serological methods for detecting infection with the HRVL agent. We also initiated studies to determine the possible mode of transmission of the HRVL agent by studying contacts of hospitalized patients. We found that 35% parents of patients with HRVL infections were also infected with the HRVL agent. Serological studies revealed that the HRVL agent was antigenically related to the Nebraska Calf Diarrhoea Virus, the epizootic diarrhoea of infant mice virus, the SA-11 virus, and the \"O\" agent."}
{"id": "PMID:186240", "title": "The activation of adenylate cyclase by cholera toxin: possible interaction with the nucleotide regulatory site.", "content": "The application of cholera toxin to intact cells causes a stimulation of adenylate cyclase activity. The effect is characterized by a lag period followed by a progressive rise in enzyme activity over several hours. Only a few minutes' exposure to the toxin is required to produce effects lasting over several days. Stimulation of adenylate cyclase by cholera toxin in broken cell preparations requires the presence of nicotinamide-adenine dinucleotide (NAD) and an unidentified component of the cytosol. Guanyl nucleotides and certain non-hydrolysable analogues of guanosine triphosphate also stimulate adenylate cyclase. Stimulation by the analogues results in a highly activated enzyme which has characterisitcs similar to those of adenylate cyclase after stimulation by cholera toxin. Thus the stimulation is irreversible, the enzyme may be \"solubilized\" by non-ionic detergents in the activated state, and responses to certain hormones are enhanced. Therefore the possibility exists that cholera toxin acts on the guanyl nucleotide regulatory protein of the adenylate cyclase complex. In exploring this possibility it was found pretreatment with cholera toxin not only blocked the stimulatory effect of subsequently added guanylylimidodi-phosphate (GppNHp) but that the latter reduced the stimulation by toxin. Similarly, pretreatment with GppNHp blocked the effect of cholera toxin. The similarities in the effects of cholera toxin and GppNHp, together with the mutual interference of their activities, suggests that cholera toxin acts at the same regulatory site at which guanyl nucleotides exert their effects on adenylate cyclase.", "contents": "The activation of adenylate cyclase by cholera toxin: possible interaction with the nucleotide regulatory site. The application of cholera toxin to intact cells causes a stimulation of adenylate cyclase activity. The effect is characterized by a lag period followed by a progressive rise in enzyme activity over several hours. Only a few minutes' exposure to the toxin is required to produce effects lasting over several days. Stimulation of adenylate cyclase by cholera toxin in broken cell preparations requires the presence of nicotinamide-adenine dinucleotide (NAD) and an unidentified component of the cytosol. Guanyl nucleotides and certain non-hydrolysable analogues of guanosine triphosphate also stimulate adenylate cyclase. Stimulation by the analogues results in a highly activated enzyme which has characterisitcs similar to those of adenylate cyclase after stimulation by cholera toxin. Thus the stimulation is irreversible, the enzyme may be \"solubilized\" by non-ionic detergents in the activated state, and responses to certain hormones are enhanced. Therefore the possibility exists that cholera toxin acts on the guanyl nucleotide regulatory protein of the adenylate cyclase complex. In exploring this possibility it was found pretreatment with cholera toxin not only blocked the stimulatory effect of subsequently added guanylylimidodi-phosphate (GppNHp) but that the latter reduced the stimulation by toxin. Similarly, pretreatment with GppNHp blocked the effect of cholera toxin. The similarities in the effects of cholera toxin and GppNHp, together with the mutual interference of their activities, suggests that cholera toxin acts at the same regulatory site at which guanyl nucleotides exert their effects on adenylate cyclase."}
{"id": "PMID:186243", "title": "Behavioral manifestations of the Kleine-Levin syndrome.", "content": "The authors present a case of the Kleine-Levin syndrome, and review the literature to assess the various ways this illness can appear. Psychiatric manifestations not only obscure the diagnosis, but may lead to inappropriate treatment.", "contents": "Behavioral manifestations of the Kleine-Levin syndrome. The authors present a case of the Kleine-Levin syndrome, and review the literature to assess the various ways this illness can appear. Psychiatric manifestations not only obscure the diagnosis, but may lead to inappropriate treatment."}
{"id": "PMID:186241", "title": "Granular-cell myoblastoma of the cercum: report of a case.", "content": "A 9-mm granular-cell myoblastoma of the cecum found incidentally during appendectomy in a 17-year-old-girl is reported. Electronmicroscopic findings favor origin of the granular cells from an undifferentiated mesenchymal (fibroblast-like) cell. Review of the small number of previously reported cases revealed three involving the cecum, one each in the ascending and transverse colon and two in the rectum. Four patients were asymptomatic and their lesions were found incidentally. Three lesions simulated maligancy clinically; these patients underwent right hemicolectomy.", "contents": "Granular-cell myoblastoma of the cercum: report of a case. A 9-mm granular-cell myoblastoma of the cecum found incidentally during appendectomy in a 17-year-old-girl is reported. Electronmicroscopic findings favor origin of the granular cells from an undifferentiated mesenchymal (fibroblast-like) cell. Review of the small number of previously reported cases revealed three involving the cecum, one each in the ascending and transverse colon and two in the rectum. Four patients were asymptomatic and their lesions were found incidentally. Three lesions simulated maligancy clinically; these patients underwent right hemicolectomy."}
{"id": "PMID:186242", "title": "Carcinoma of anal-ductal origin: report of a case.", "content": "A 57-year-old man who had a carcinoma proven to be of anal ductal origin is presented. Recurrent perianal fistulas were treated locally for two years until biopsy proved the malignancy. Gross and histologic examination of the specimen removed by abdominoperineal resection demonstrated the anal ductal origin of this tumor. Recurrence was seen in less than a year.", "contents": "Carcinoma of anal-ductal origin: report of a case. A 57-year-old man who had a carcinoma proven to be of anal ductal origin is presented. Recurrent perianal fistulas were treated locally for two years until biopsy proved the malignancy. Gross and histologic examination of the specimen removed by abdominoperineal resection demonstrated the anal ductal origin of this tumor. Recurrence was seen in less than a year."}
{"id": "PMID:186248", "title": "[The neuroendocrinology of sleep].", "content": "It is now well established that some pituitary hormones have a pattern of secretion closely linked to the sleep-waking cycle. These data open a new approach to the problem of sleep disturbances and suppose a completely new evaluation of their meaning.", "contents": "[The neuroendocrinology of sleep]. It is now well established that some pituitary hormones have a pattern of secretion closely linked to the sleep-waking cycle. These data open a new approach to the problem of sleep disturbances and suppose a completely new evaluation of their meaning."}
{"id": "PMID:186247", "title": "[The effects of calcitonin, glucagon and the dibutyryl derivative of cyclic AMP on plasma-renin activity (author's transl)].", "content": "Infusion of 2 MRC/kg X h calcitonin in anaesthetised dogs produced a significant increase in plasma-renin activity, clearance of 51Dr-EDTA and 125I-o-iodohipuric acid, heart rate and urinary excretion of sodium, potassium, calcium and phosphates, while serum electrolytes and mean arterial pressure markedly fell. Infusion of 5 mug/kg X min glucagon produced a significant fall of plasma-renin, heart rate rose, but arterial mean pressure fell, and serum and urinary electrolytes did not change significantly, Cyclic AMP (dibutyryl-cAMP) significantly stimulated renin at a dose of 5 mg/min, while there were no significant changes in blood pressure, heart rate and serum and urinary electrolytes.", "contents": "[The effects of calcitonin, glucagon and the dibutyryl derivative of cyclic AMP on plasma-renin activity (author's transl)]. Infusion of 2 MRC/kg X h calcitonin in anaesthetised dogs produced a significant increase in plasma-renin activity, clearance of 51Dr-EDTA and 125I-o-iodohipuric acid, heart rate and urinary excretion of sodium, potassium, calcium and phosphates, while serum electrolytes and mean arterial pressure markedly fell. Infusion of 5 mug/kg X min glucagon produced a significant fall of plasma-renin, heart rate rose, but arterial mean pressure fell, and serum and urinary electrolytes did not change significantly, Cyclic AMP (dibutyryl-cAMP) significantly stimulated renin at a dose of 5 mg/min, while there were no significant changes in blood pressure, heart rate and serum and urinary electrolytes."}
{"id": "PMID:186246", "title": "[Idiopathic hypophosphataemic osteomalacia (author's transl)].", "content": "In an adult with sporadic idiopathic osteomalacia an increased phosphate clearance, hypophosphataemia, normocalcaemia, normal serum-25-hydroxycalciferol and an only slightly increased immunoreactive parathormone were found. Intestinal 47Ca absorption was clearly decreased. Radiologically and histologically there was a clear-cut defect of skeletal mineralisation. Under treatment with daily doses of 1-1.25 mg of vitamin D3 the 25-hydroxycalciferol level increased markedly, the immunoreactive parathormone decreased slightly. Serum calcium and hypophosphataemia remained unchanged and intestinal 47Ca absorption was improved. Already 4 weeks after commencing treatment pain and defective gait of the patient disappeared. Radiologically skeletal changes were improved after 7 months. However, histologically no significant bone healing had occurred. The biochemical findings of this disease correspond to those of familial hypophosphataemic (vitamin-D-resistant) rickets. The therapeutic effects of pharmacological doses of vitamin D resemble those in pseudo-vitamin-D-deficient rickets. The pathogenesis of idiopathic osteomalacia of the adult remains unclear. Vitamin D metabolism is unchanged as far as the stage of 25-hydroxycholecalciferol. It is unknown if a disorder of the renal synthesis of 1,25-dihydroxycholecalciferol or a peripheral resistance to the effects of this metabolite exists. In addition a defect of the tubular phosphate reabsorption independent of parathormone and vitamin D is assumed.", "contents": "[Idiopathic hypophosphataemic osteomalacia (author's transl)]. In an adult with sporadic idiopathic osteomalacia an increased phosphate clearance, hypophosphataemia, normocalcaemia, normal serum-25-hydroxycalciferol and an only slightly increased immunoreactive parathormone were found. Intestinal 47Ca absorption was clearly decreased. Radiologically and histologically there was a clear-cut defect of skeletal mineralisation. Under treatment with daily doses of 1-1.25 mg of vitamin D3 the 25-hydroxycalciferol level increased markedly, the immunoreactive parathormone decreased slightly. Serum calcium and hypophosphataemia remained unchanged and intestinal 47Ca absorption was improved. Already 4 weeks after commencing treatment pain and defective gait of the patient disappeared. Radiologically skeletal changes were improved after 7 months. However, histologically no significant bone healing had occurred. The biochemical findings of this disease correspond to those of familial hypophosphataemic (vitamin-D-resistant) rickets. The therapeutic effects of pharmacological doses of vitamin D resemble those in pseudo-vitamin-D-deficient rickets. The pathogenesis of idiopathic osteomalacia of the adult remains unclear. Vitamin D metabolism is unchanged as far as the stage of 25-hydroxycholecalciferol. It is unknown if a disorder of the renal synthesis of 1,25-dihydroxycholecalciferol or a peripheral resistance to the effects of this metabolite exists. In addition a defect of the tubular phosphate reabsorption independent of parathormone and vitamin D is assumed."}
{"id": "PMID:186249", "title": "Hormone-induced dispersion or aggregation of carotenoid-containing smooth endoplasmic reticulum in cultured xanthophores from the goldfish, Carrassius auratus L.", "content": "A novel organelle movement is described in goldfish xanthophores. Smooth endoplasmic reticulum, containing carotenoids pigments, undergo MSH or c-AMP-induced dispersion. This dispersion is independent of RNA and protein synthesis, not modulated by c-GMP and inhibited by cytochalasin B but only at the relatively high concentration of 10 mug/ml. Epinephrine induces aggregation, a process that is inhibited by colchicine. These results suggest, but do not prove, the involvement of microfilaments in dispersion and microtubules in the aggregation of carotenoid-containing endoplasmic reticulum.", "contents": "Hormone-induced dispersion or aggregation of carotenoid-containing smooth endoplasmic reticulum in cultured xanthophores from the goldfish, Carrassius auratus L. A novel organelle movement is described in goldfish xanthophores. Smooth endoplasmic reticulum, containing carotenoids pigments, undergo MSH or c-AMP-induced dispersion. This dispersion is independent of RNA and protein synthesis, not modulated by c-GMP and inhibited by cytochalasin B but only at the relatively high concentration of 10 mug/ml. Epinephrine induces aggregation, a process that is inhibited by colchicine. These results suggest, but do not prove, the involvement of microfilaments in dispersion and microtubules in the aggregation of carotenoid-containing endoplasmic reticulum."}
{"id": "PMID:186250", "title": "Regulation of lactogen specific binding sites in rat liver: studies on the role of lactogens and estrogen.", "content": "Regulation of the lactogen specific binding sites of rat liver was studied in several different high lactogen states. The specific binding of [125I]iodo-hGH was determined as a measure of these sites. Hypophysectomy of pregnant rats produced a much smaller decrease in hepatic binding of [125I]iodo-hGH than was seen in nonpregnant females. Three different prolactin secreting tumors (MtT/F4, MtT/F45, MtT/W5) produced greatly elevated levels of both rPRL and hepatic binding of [125I]iodo-hGH in both male and female rats. The increased binding reflected an increase in the concentration of lactogen specific membrane binding sites. There was no change in the apparent affinity of binding. Hypophysectomy of tumor-bearing rats was not followed by a decrease in the concentration of hepatic sites. Pituitary transplants beneath the kidney capsules of hypophysectomized (hypox) rats produced elevated rPRL levels and increased [125I]iod-GH specific binding to hepatic membranes. The elevation of serum rPRL preceded the increase in hepatic binding. There was a direct correlation between rPRL levels attained by 8 days after implantation and the level of hepatic binding. Estrogen treatment did not alter this correlation. Hormonal replacement with prolactin in combination with various hormones failed to induce the lactogen specific hepatic sites in estrogen treated hypox males, and did not prevent the marked decrease in hepatic binding observed in females following hypophysectomy. It is suggested that chronic elevation of prolactin plays a role in inducing lactogen specific binding sites in rat liver. Estrogen's inductive action seems to be largely effected at the pituitary level.", "contents": "Regulation of lactogen specific binding sites in rat liver: studies on the role of lactogens and estrogen. Regulation of the lactogen specific binding sites of rat liver was studied in several different high lactogen states. The specific binding of [125I]iodo-hGH was determined as a measure of these sites. Hypophysectomy of pregnant rats produced a much smaller decrease in hepatic binding of [125I]iodo-hGH than was seen in nonpregnant females. Three different prolactin secreting tumors (MtT/F4, MtT/F45, MtT/W5) produced greatly elevated levels of both rPRL and hepatic binding of [125I]iodo-hGH in both male and female rats. The increased binding reflected an increase in the concentration of lactogen specific membrane binding sites. There was no change in the apparent affinity of binding. Hypophysectomy of tumor-bearing rats was not followed by a decrease in the concentration of hepatic sites. Pituitary transplants beneath the kidney capsules of hypophysectomized (hypox) rats produced elevated rPRL levels and increased [125I]iod-GH specific binding to hepatic membranes. The elevation of serum rPRL preceded the increase in hepatic binding. There was a direct correlation between rPRL levels attained by 8 days after implantation and the level of hepatic binding. Estrogen treatment did not alter this correlation. Hormonal replacement with prolactin in combination with various hormones failed to induce the lactogen specific hepatic sites in estrogen treated hypox males, and did not prevent the marked decrease in hepatic binding observed in females following hypophysectomy. It is suggested that chronic elevation of prolactin plays a role in inducing lactogen specific binding sites in rat liver. Estrogen's inductive action seems to be largely effected at the pituitary level."}
{"id": "PMID:186251", "title": "Inhibitory and facilitatory areas of the dorsal medulla mediating ACTH release in the cat.", "content": "To define the role of the dorsal medulla in the control of release of ACTH, the authors stimulated electrically (30 sec, 100 muA, 50 Hz) 50 sites in the vicinity of the solitary nuclei of 11 cats anesthetized with chloralose/urethane. Responses of arterial pressure to electrical stimulation were not correlated significantly with release of ACTH. Indirect effects of changes in arterial pressure could not explain changes in release of ACTH. Concentrations of ACTH were measured by radioimmunoassay. Active areas associated with the solitary nucleus were : 1) lateral inhibitory: ventral and lateral to the solitary tract (mean delta ACTH:-153, -86, -97 pg/ml at 1.5, 3.0 and 6.0 min respectively; P less than 0.01); 2) medial inhibitory: medial dorsal motor nucleus of the vagus and extending to the midline (mean delta ACTH: -81, -107, -67 pg/ml; P less than 0.01); and 3) intermediate facilitatory: lateral nucleus intercalatus and adjacent reticular formation (mean delta ACTH: +105, +158, +4 pg/ml; P less than 0.01). The former two areas contain neurons activated by atrial stretch, and the latter area contains neurons inhibited by atrial stretch. Since changes in ACTH levels are inversely correlated with atrial stretch, the results suggest that the changes in release of ACTH are the result of direct stimulation of neural systems of the solitary nuclei mediating release of ACTH in response to hemodynamic changes.", "contents": "Inhibitory and facilitatory areas of the dorsal medulla mediating ACTH release in the cat. To define the role of the dorsal medulla in the control of release of ACTH, the authors stimulated electrically (30 sec, 100 muA, 50 Hz) 50 sites in the vicinity of the solitary nuclei of 11 cats anesthetized with chloralose/urethane. Responses of arterial pressure to electrical stimulation were not correlated significantly with release of ACTH. Indirect effects of changes in arterial pressure could not explain changes in release of ACTH. Concentrations of ACTH were measured by radioimmunoassay. Active areas associated with the solitary nucleus were : 1) lateral inhibitory: ventral and lateral to the solitary tract (mean delta ACTH:-153, -86, -97 pg/ml at 1.5, 3.0 and 6.0 min respectively; P less than 0.01); 2) medial inhibitory: medial dorsal motor nucleus of the vagus and extending to the midline (mean delta ACTH: -81, -107, -67 pg/ml; P less than 0.01); and 3) intermediate facilitatory: lateral nucleus intercalatus and adjacent reticular formation (mean delta ACTH: +105, +158, +4 pg/ml; P less than 0.01). The former two areas contain neurons activated by atrial stretch, and the latter area contains neurons inhibited by atrial stretch. Since changes in ACTH levels are inversely correlated with atrial stretch, the results suggest that the changes in release of ACTH are the result of direct stimulation of neural systems of the solitary nuclei mediating release of ACTH in response to hemodynamic changes."}
{"id": "PMID:186252", "title": "Inhibitory and facilitatory areas of the rostral pons mediating ACTH release in the cat.", "content": "To define the role of the rostral pons in the control of release of ACTH, we stimulated electrically (30 sec, 200 muA, 50 Hz) 128 sites in the dorsal rostral pons of 20 cats anesthetized with chloralose/urethane. Responses of arterial pressure to electrical stimulation were prevented by lesions placed previously in the medulla. Plasma concentrations of ACTH were measured by radioimmunoassay. Active areas consisted of three regions: 1) lateral inhibitory: Locus subcoeruleus and anteroventral locus coeruleus (mean deltaACTH: -189, -164, -145 pg/ml at 1.5,3.0 and 6.0 min respectively, P less than 0.01);2) intermediate facilitatory:principal locus coeruleus and lateral ventral tegmental nucleus (mean deltaACTH: +81, +68, +37 pg/ml; P less than 0.05); and 3) medial inhibitory: dorsal tegmental nucleus, dorsal raph\u00e9 and medial ventral tegmental nucleus (mean deltaACTH; -211, -212, -115 pg/ml; P less than 0.01). The former two areas received direct projections from medullary neurons activated or inhibited by atrial stretch, and, in turn, give rise to adrenergic and cholinergic projections to the medial hypothalamus. Since the release of ACTH is inversely correlated with right atrial stretch, the results suggest that the lateral inhibitory area and the intermediate facilitatory area are involved in mediation of changes in release of ACTH in response to hemodynamic changes.", "contents": "Inhibitory and facilitatory areas of the rostral pons mediating ACTH release in the cat. To define the role of the rostral pons in the control of release of ACTH, we stimulated electrically (30 sec, 200 muA, 50 Hz) 128 sites in the dorsal rostral pons of 20 cats anesthetized with chloralose/urethane. Responses of arterial pressure to electrical stimulation were prevented by lesions placed previously in the medulla. Plasma concentrations of ACTH were measured by radioimmunoassay. Active areas consisted of three regions: 1) lateral inhibitory: Locus subcoeruleus and anteroventral locus coeruleus (mean deltaACTH: -189, -164, -145 pg/ml at 1.5,3.0 and 6.0 min respectively, P less than 0.01);2) intermediate facilitatory:principal locus coeruleus and lateral ventral tegmental nucleus (mean deltaACTH: +81, +68, +37 pg/ml; P less than 0.05); and 3) medial inhibitory: dorsal tegmental nucleus, dorsal raph\u00e9 and medial ventral tegmental nucleus (mean deltaACTH; -211, -212, -115 pg/ml; P less than 0.01). The former two areas received direct projections from medullary neurons activated or inhibited by atrial stretch, and, in turn, give rise to adrenergic and cholinergic projections to the medial hypothalamus. Since the release of ACTH is inversely correlated with right atrial stretch, the results suggest that the lateral inhibitory area and the intermediate facilitatory area are involved in mediation of changes in release of ACTH in response to hemodynamic changes."}
{"id": "PMID:186253", "title": "Concentration of cyclic AMP in rat liver as a function of the insulin/glucagon ratio in blood under standardized physiological conditions.", "content": "The concentration of insulin and glucagon in peripheral blood and the concentration of cAMP in liver was followed in rats throughout a 48 hour starvation period and up to 6 hours afer refeeding glucose or casein. By so changing the insulin/glucagon molar ratio from minimum to maximum values, simultaneous inverse changes in the concentration of hepatic cAMP could be induced. The study, thus, suggests that during a starvation-refeeding cycle the level of cAMP in the liver is regulated predominantly by the insulin/glucagon ratio in the blood. Possible criticisms of this conclusion are discussed.", "contents": "Concentration of cyclic AMP in rat liver as a function of the insulin/glucagon ratio in blood under standardized physiological conditions. The concentration of insulin and glucagon in peripheral blood and the concentration of cAMP in liver was followed in rats throughout a 48 hour starvation period and up to 6 hours afer refeeding glucose or casein. By so changing the insulin/glucagon molar ratio from minimum to maximum values, simultaneous inverse changes in the concentration of hepatic cAMP could be induced. The study, thus, suggests that during a starvation-refeeding cycle the level of cAMP in the liver is regulated predominantly by the insulin/glucagon ratio in the blood. Possible criticisms of this conclusion are discussed."}
{"id": "PMID:186254", "title": "Studies on the mechanism of the antilipolytic effects of growth hormone.", "content": "Ovine growth hormone (1 mug/ml) antagonized the lipolytic action of epinephrine (0.25 mug/ml) in segments of adipose tissue obtained from hypophysectomized rats, but a lag period of about 10 min was required. When added simultaneously with epinephrine, growth hormone neither reduced the maximal accumulation of cyclic AMP which occurred at 3 min nor accelerated the return to basal levels. Only when tissues were exposed to epinephrine 15 min after preincubation with growth hormone was cyclic AMP accumulation compromised. Growth hormone also produced a delayed increase of about 20% in the activity of a low Km cyclic nucleotide phosphodiesterase, which might have contributed to the decrease in cyclic AMP accumulation. The increase in phosphodiesterase activity probably did not account for the antilipolytic effect, however, since antilipolysis was evident before the increase in phosphodiesterase activity could be  detected. The antilipolytic effects of growth hormone similarly could not be attributed to the decrease in cyclic AMP concentrations, for when added simultaneously with epinephrine the antilipolytic effects did not occur until after the evanescent changes in cyclic AMP had passed. Growth hormone added simultaneously with epinephrine or 30 min later significantly decreased the activity of protein kinase assayed in the absence of exogenous cyclic AMP, but did not change total protein kinase activity as measured in the presence of a saturating concentration of cyclic AMP. This effect of growth hormone was evident as early as 3 min after addition of the hormone and may at least partially account for the antilipolytic effect.", "contents": "Studies on the mechanism of the antilipolytic effects of growth hormone. Ovine growth hormone (1 mug/ml) antagonized the lipolytic action of epinephrine (0.25 mug/ml) in segments of adipose tissue obtained from hypophysectomized rats, but a lag period of about 10 min was required. When added simultaneously with epinephrine, growth hormone neither reduced the maximal accumulation of cyclic AMP which occurred at 3 min nor accelerated the return to basal levels. Only when tissues were exposed to epinephrine 15 min after preincubation with growth hormone was cyclic AMP accumulation compromised. Growth hormone also produced a delayed increase of about 20% in the activity of a low Km cyclic nucleotide phosphodiesterase, which might have contributed to the decrease in cyclic AMP accumulation. The increase in phosphodiesterase activity probably did not account for the antilipolytic effect, however, since antilipolysis was evident before the increase in phosphodiesterase activity could be  detected. The antilipolytic effects of growth hormone similarly could not be attributed to the decrease in cyclic AMP concentrations, for when added simultaneously with epinephrine the antilipolytic effects did not occur until after the evanescent changes in cyclic AMP had passed. Growth hormone added simultaneously with epinephrine or 30 min later significantly decreased the activity of protein kinase assayed in the absence of exogenous cyclic AMP, but did not change total protein kinase activity as measured in the presence of a saturating concentration of cyclic AMP. This effect of growth hormone was evident as early as 3 min after addition of the hormone and may at least partially account for the antilipolytic effect."}
{"id": "PMID:186255", "title": "Studies on oxidative phosphorylation and steroidogenesis by ovarian mitochondria after gonadotropic stimulation.", "content": "No differences in oxidative phosphorylation or in the per cent of [4-14C]progesterone were found in ovarian mitochondria of immature rats after treatment with 20 IU of pregnant mare serum gonadotropin (PMSG) iv 30 min before killing. However, treatment of immature rats with 20 IU of PMSG sc 54 h prior to killing decreased the ADP:O ratio and increased the per cent of [4-14C]cholesterol conversion. Electron microscopic studies showed that mitochondria with lamellar cristae were prominent in ovaries of untreated rats, while large pleomorphic mitochondria and mitochondria with tubulovesicular cristae dominated in ovaries of PMSG-treated rats. Ovarian homogenates separated by zonal centrifugation showed three peaks od cytochrome oxidase activity which shifted to the heavier end of the gradient after PMSG treatment. These studies suggest that PMSG treatment influences ovarian mitochondria, possibly by stimulating the synthesis of additional functional components and/or the biogenesis of new mitochondria. Aminoglutethimide addition to bovine luteal mitochondria decreased steroidogenesis by 60% when succinate was used as substrate. However, there was a 16% increase in the ADP:O ratio, apparently due to a decrease in oxygen utilization. When oligomycin was added to luteal mitochondria, there was a 30% decrease in the ACP:O ratio but a 300% increase in [4-14C]cholesterol conversion. Dinitrophenol also decreased mitochondrial steroidogenesis. These results suggest that energy obtained from succinate oxidation can be diverted from phosphorylation to support steroidogenesis.", "contents": "Studies on oxidative phosphorylation and steroidogenesis by ovarian mitochondria after gonadotropic stimulation. No differences in oxidative phosphorylation or in the per cent of [4-14C]progesterone were found in ovarian mitochondria of immature rats after treatment with 20 IU of pregnant mare serum gonadotropin (PMSG) iv 30 min before killing. However, treatment of immature rats with 20 IU of PMSG sc 54 h prior to killing decreased the ADP:O ratio and increased the per cent of [4-14C]cholesterol conversion. Electron microscopic studies showed that mitochondria with lamellar cristae were prominent in ovaries of untreated rats, while large pleomorphic mitochondria and mitochondria with tubulovesicular cristae dominated in ovaries of PMSG-treated rats. Ovarian homogenates separated by zonal centrifugation showed three peaks od cytochrome oxidase activity which shifted to the heavier end of the gradient after PMSG treatment. These studies suggest that PMSG treatment influences ovarian mitochondria, possibly by stimulating the synthesis of additional functional components and/or the biogenesis of new mitochondria. Aminoglutethimide addition to bovine luteal mitochondria decreased steroidogenesis by 60% when succinate was used as substrate. However, there was a 16% increase in the ADP:O ratio, apparently due to a decrease in oxygen utilization. When oligomycin was added to luteal mitochondria, there was a 30% decrease in the ACP:O ratio but a 300% increase in [4-14C]cholesterol conversion. Dinitrophenol also decreased mitochondrial steroidogenesis. These results suggest that energy obtained from succinate oxidation can be diverted from phosphorylation to support steroidogenesis."}
{"id": "PMID:186256", "title": "On the possible role of thiol groups in the insulin-releasing action of mercurials, organic disulfides, alkylating agents, and sulfonylureas.", "content": "The thiol activity of pancreatic islets was spectrophotometrically assayed as the formation of 6-mercaptonicotinic acid from the organic disulfide, 6,6'-dithiodinicotinic acid. Islets containing more than 90% beta-cells were microdissected from non-inbred ob/ob-mice. Comparisons of intact with homogenized islets indicated that the organic disulfide penetrates relatively slowly into the beta-cells. When tested at concentrations know to enhance insulin release, p-chloromercuribenzene-sulfonic acid almost completely blocked the thiol activity of intact islets, whereas no significant effect was observed with iodoacetamide, D-glucose, or glibenclamide. Although glibenclamide had no demonstrable effect on the thiol activity of free L-cysteine, the binding of glibenclamide to serum albumin was decreased by blocking the albumin thiols with azobenzene-2-sulfenyl bromide. The uptake of glibenclamide by pancreatic islets was inhibited by cysteine or reduced glutathione. Cysteine, as well as 6,6'-dithiodinicotinic acid, also seemed to interact negatively with glibenat organic mercurials and disulfides stimulate insulin release by blocking thiol groups in the beta-cell plasma membranes. The thiol groups involved in iodoacetamide-induced secretion may escape detection by the assay employed, or target groups other than thiols may be involved. The data on glibenclamide are compatible with, but do not unequivocally support, the notion that thiol groups may play a role in sulfonylurea-induced insulin release.", "contents": "On the possible role of thiol groups in the insulin-releasing action of mercurials, organic disulfides, alkylating agents, and sulfonylureas. The thiol activity of pancreatic islets was spectrophotometrically assayed as the formation of 6-mercaptonicotinic acid from the organic disulfide, 6,6'-dithiodinicotinic acid. Islets containing more than 90% beta-cells were microdissected from non-inbred ob/ob-mice. Comparisons of intact with homogenized islets indicated that the organic disulfide penetrates relatively slowly into the beta-cells. When tested at concentrations know to enhance insulin release, p-chloromercuribenzene-sulfonic acid almost completely blocked the thiol activity of intact islets, whereas no significant effect was observed with iodoacetamide, D-glucose, or glibenclamide. Although glibenclamide had no demonstrable effect on the thiol activity of free L-cysteine, the binding of glibenclamide to serum albumin was decreased by blocking the albumin thiols with azobenzene-2-sulfenyl bromide. The uptake of glibenclamide by pancreatic islets was inhibited by cysteine or reduced glutathione. Cysteine, as well as 6,6'-dithiodinicotinic acid, also seemed to interact negatively with glibenat organic mercurials and disulfides stimulate insulin release by blocking thiol groups in the beta-cell plasma membranes. The thiol groups involved in iodoacetamide-induced secretion may escape detection by the assay employed, or target groups other than thiols may be involved. The data on glibenclamide are compatible with, but do not unequivocally support, the notion that thiol groups may play a role in sulfonylurea-induced insulin release."}
{"id": "PMID:186257", "title": "Effects of ACTH on plasma levels of adrenal steroids in essential hypertension.", "content": "Plasma concentrations of progesterone (P), deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OH P), corticosterone (B), deoxycortisol (S), cortisol (F) and aldosterone (A) in 8 control subjects (mean age: 40.5 years) and 10 patients with essential hypertension (EH) (mean age: 48.5 years) were determined before, 4 and 8 hours after an infusion of ACTH at a rate of 25 units per 8 hours. Secretion rates (SR) of 18-hydroxy-11-deoxycorticosterone (18-OH DOC) were measured 24 hours before and again on the day of ACTH infusion. All subjects were studied on the fourth day of a diet containing 135 mEq of sodium and 90 mEq of potassium. There was no statistically significant difference between 8 control subjects and 10 patients with EH in the 7 plasma steroid levels and the SR of 18-OH DOC before ACTH infusion. The mean plasma P response to ACTH was slightly lower in controls than in patients with EH, while that of 17-OH P (in male subjects) was slightly higher. The mean plasma B response was significantly lower after 4 hours of ACTH infusion (p less than 0.01), while that of DOC was significantly higher after 8 hours of ACTH infusion (p less than 0.05) in patients with EH. The mean plasma S rose significantly more in patients with EH (p less than 0.025) at 4 and 8 hours after ACTH infusion. The mean plasma F response to ACTH infusion was slightly lower in patients with EH than in controls. The mean response of 18-OH DOC SR to ACTH infusion was slightly higher in patients with EH than in controls. The mean plasma A response was significantly higher in patients with EH than in controls 4 (p less than 0.05) and 8 hour (p less than 0.001) after an ACTH infusion. These results could be explained in part by abnormalities in the 17- and 11-hydroxylase systems, and that the abnormality in 11-hydroxylation was more pronounced than that in the 17-position. Furthermore, we suspect that the sensitivity of adrenal aldosterone to ACTH might be increased or another accelerated pathway to aldosterone biosynthesis might exist in patients with EH.", "contents": "Effects of ACTH on plasma levels of adrenal steroids in essential hypertension. Plasma concentrations of progesterone (P), deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OH P), corticosterone (B), deoxycortisol (S), cortisol (F) and aldosterone (A) in 8 control subjects (mean age: 40.5 years) and 10 patients with essential hypertension (EH) (mean age: 48.5 years) were determined before, 4 and 8 hours after an infusion of ACTH at a rate of 25 units per 8 hours. Secretion rates (SR) of 18-hydroxy-11-deoxycorticosterone (18-OH DOC) were measured 24 hours before and again on the day of ACTH infusion. All subjects were studied on the fourth day of a diet containing 135 mEq of sodium and 90 mEq of potassium. There was no statistically significant difference between 8 control subjects and 10 patients with EH in the 7 plasma steroid levels and the SR of 18-OH DOC before ACTH infusion. The mean plasma P response to ACTH was slightly lower in controls than in patients with EH, while that of 17-OH P (in male subjects) was slightly higher. The mean plasma B response was significantly lower after 4 hours of ACTH infusion (p less than 0.01), while that of DOC was significantly higher after 8 hours of ACTH infusion (p less than 0.05) in patients with EH. The mean plasma S rose significantly more in patients with EH (p less than 0.025) at 4 and 8 hours after ACTH infusion. The mean plasma F response to ACTH infusion was slightly lower in patients with EH than in controls. The mean response of 18-OH DOC SR to ACTH infusion was slightly higher in patients with EH than in controls. The mean plasma A response was significantly higher in patients with EH than in controls 4 (p less than 0.05) and 8 hour (p less than 0.001) after an ACTH infusion. These results could be explained in part by abnormalities in the 17- and 11-hydroxylase systems, and that the abnormality in 11-hydroxylation was more pronounced than that in the 17-position. Furthermore, we suspect that the sensitivity of adrenal aldosterone to ACTH might be increased or another accelerated pathway to aldosterone biosynthesis might exist in patients with EH."}
{"id": "PMID:186258", "title": "Plasma immunoassayable ACTH levels during and after hydrocortisone infusion in patients with Cushing's disease.", "content": "The plasma ACTH responses to hydrocortisone infusion were compared in patients with Cushing's disease and primary adrenocortical insufficiency. In 4 patients with primary adrenocortical insufficiency, plasma ACTH levels were suppressed exponentially after administration of a relatively large dose of hydrocortisone (1.0 mg/kg/1.5 hr-3.0 mg/kg/2 hr). In patients with post-adrenalectomized Cushing's disease (4, bilateral; 1, unilateral), plasma ACTH suppression was delayed. Plasma ACTH levels, expressed as a percentage of the basal concentrations, were significantly less suppressed in patients with Cushing's disease than in patients with primary adrenocortical insufficiency 90 (p less than 0.05) and 120 (p less than 0.05) min after the beginning of infusion. When 0.5 mg/kg hydrocortisone was infused over a period of 1.5 hr, suppression was also delayed in Cushing's disease, and plasma ACTH levels were less suppressed in 4 patients with Cushing's disease than in 4 patients with primary adrenocortical insufficiency at 30 (p greater than 0.05), 45 (p greater than 0.05) 60 (p less than 0.05) min.", "contents": "Plasma immunoassayable ACTH levels during and after hydrocortisone infusion in patients with Cushing's disease. The plasma ACTH responses to hydrocortisone infusion were compared in patients with Cushing's disease and primary adrenocortical insufficiency. In 4 patients with primary adrenocortical insufficiency, plasma ACTH levels were suppressed exponentially after administration of a relatively large dose of hydrocortisone (1.0 mg/kg/1.5 hr-3.0 mg/kg/2 hr). In patients with post-adrenalectomized Cushing's disease (4, bilateral; 1, unilateral), plasma ACTH suppression was delayed. Plasma ACTH levels, expressed as a percentage of the basal concentrations, were significantly less suppressed in patients with Cushing's disease than in patients with primary adrenocortical insufficiency 90 (p less than 0.05) and 120 (p less than 0.05) min after the beginning of infusion. When 0.5 mg/kg hydrocortisone was infused over a period of 1.5 hr, suppression was also delayed in Cushing's disease, and plasma ACTH levels were less suppressed in 4 patients with Cushing's disease than in 4 patients with primary adrenocortical insufficiency at 30 (p greater than 0.05), 45 (p greater than 0.05) 60 (p less than 0.05) min."}
{"id": "PMID:186259", "title": "Enzymatic radioiodination of succinyl cyclic AMP tyrosine methyl ester by lactoperoxidase and radioimmunoassay for cyclic AMP.", "content": "A highly specific and simple radioimmunoassay for cyclic AMP with a sensitivity of 0.04 picomoles/tube has been developed according to the method of Steiner et al., using 125I-succinyl cyclic AMP tyrosine methyl ester as a tracer. The tracer with higher immunoactivities could be simply and constantly prepared by an enzymatic iodination procedure utilizing lactoperoxidase, radioactive iodide and hydrogen peroxide generated by glucose-glucose oxidase system, rather than by chloramine-T procedure.", "contents": "Enzymatic radioiodination of succinyl cyclic AMP tyrosine methyl ester by lactoperoxidase and radioimmunoassay for cyclic AMP. A highly specific and simple radioimmunoassay for cyclic AMP with a sensitivity of 0.04 picomoles/tube has been developed according to the method of Steiner et al., using 125I-succinyl cyclic AMP tyrosine methyl ester as a tracer. The tracer with higher immunoactivities could be simply and constantly prepared by an enzymatic iodination procedure utilizing lactoperoxidase, radioactive iodide and hydrogen peroxide generated by glucose-glucose oxidase system, rather than by chloramine-T procedure."}
{"id": "PMID:186261", "title": "Effects of lipolytic and antilipolytic drugs on metabolism of adenosine 3':5'-monophosphate in brown adipose tissue of cold acclimated rats.", "content": "The intracellular level of adenosine 3':5'-monophosphate (cyclic AMP) and its stimulation in vitro by norepinephrine were studied in brown and white adipocytes from rats adapted to constant or fluctuating cold. Cold acclimatization had no effect on the basal cyclic AMP intracellular content in both tissues, but the level in brown adipocytes was four-fold higher than in the white ones. Addition of norepinephrine in the incubation medium doubled the cyclic AMP content of white adipocytes from control or fluctuating-cold-adapted rats, and enhanced four-fold in constant-cold-adapted rats. In brown adipocytes norepinephrine increased cyclic AMP levels in the first two groups, but had no effects in constant-cold-adapted rats. In the two tissues of control and fluctuating-cold-adapted rats the norepinephrine action was increased by phentolamine and decreased by propranolol. The lack of response to norepinephrine of brown adipocytes from constant cold-adapted rats was not due to the predominance of the alpha component of hormone receptors. Antilipolytic drugs (nicotinic acid, insulin and prostaglandin E2) inhibited the action of norepinephrine on white adipocytes; only prostaglandin E2 had an effect on brown ones.", "contents": "Effects of lipolytic and antilipolytic drugs on metabolism of adenosine 3':5'-monophosphate in brown adipose tissue of cold acclimated rats. The intracellular level of adenosine 3':5'-monophosphate (cyclic AMP) and its stimulation in vitro by norepinephrine were studied in brown and white adipocytes from rats adapted to constant or fluctuating cold. Cold acclimatization had no effect on the basal cyclic AMP intracellular content in both tissues, but the level in brown adipocytes was four-fold higher than in the white ones. Addition of norepinephrine in the incubation medium doubled the cyclic AMP content of white adipocytes from control or fluctuating-cold-adapted rats, and enhanced four-fold in constant-cold-adapted rats. In brown adipocytes norepinephrine increased cyclic AMP levels in the first two groups, but had no effects in constant-cold-adapted rats. In the two tissues of control and fluctuating-cold-adapted rats the norepinephrine action was increased by phentolamine and decreased by propranolol. The lack of response to norepinephrine of brown adipocytes from constant cold-adapted rats was not due to the predominance of the alpha component of hormone receptors. Antilipolytic drugs (nicotinic acid, insulin and prostaglandin E2) inhibited the action of norepinephrine on white adipocytes; only prostaglandin E2 had an effect on brown ones."}
{"id": "PMID:186263", "title": "Nuclear-magnetic-relaxation studies of the interaction of inhibitor with the threonine-sensitive aspartokinase of Escherichia coli.", "content": "The nature of the feedback inhibition of the bifunctional enzyme, aspartokinase I-homoserine dehydrogenase I of Escherichia coli was studied using 13C nuclear magnetic resonance (NMR). Since aspartokinase is activated by Mn(II), the interaction of the inhibitor L-threonine (specifically enriched to 90% 13C in the carboxyl carbon) with the metal-enzyme complex was studied. Spin-lattice (T1) and spin-spin (T2) relaxation times were determined by the partially relaxed Fourier transform method and line-width measurements respectively at 20 MHz. The pronounced broadening of the DL-threonine carboxyl peak in the presence of the Mn(II)-enzyme complex indicates that an L-threonine binding site is close to the metal binding site of the kinase active site. The non-identity of (T1)*M and (T2)*M indicates that conditions of fast exchange prevail. The (T1)*M/(T2)*M ratio was used to estimate a correlation time of 2.0 ns for the dipolar interaction at 25 degrees C. An estimate for the distance between Mn(II) and the threonine carboxyl carbon of 4.4 A (0.44 nm) was obtained. This 13C NMR study has thus located one of the two classes of threonine regulatory sites which exist per subunit; the threonine site identified here is at the aspartokinase active site, adjacent to the catalytic metal site.", "contents": "Nuclear-magnetic-relaxation studies of the interaction of inhibitor with the threonine-sensitive aspartokinase of Escherichia coli. The nature of the feedback inhibition of the bifunctional enzyme, aspartokinase I-homoserine dehydrogenase I of Escherichia coli was studied using 13C nuclear magnetic resonance (NMR). Since aspartokinase is activated by Mn(II), the interaction of the inhibitor L-threonine (specifically enriched to 90% 13C in the carboxyl carbon) with the metal-enzyme complex was studied. Spin-lattice (T1) and spin-spin (T2) relaxation times were determined by the partially relaxed Fourier transform method and line-width measurements respectively at 20 MHz. The pronounced broadening of the DL-threonine carboxyl peak in the presence of the Mn(II)-enzyme complex indicates that an L-threonine binding site is close to the metal binding site of the kinase active site. The non-identity of (T1)*M and (T2)*M indicates that conditions of fast exchange prevail. The (T1)*M/(T2)*M ratio was used to estimate a correlation time of 2.0 ns for the dipolar interaction at 25 degrees C. An estimate for the distance between Mn(II) and the threonine carboxyl carbon of 4.4 A (0.44 nm) was obtained. This 13C NMR study has thus located one of the two classes of threonine regulatory sites which exist per subunit; the threonine site identified here is at the aspartokinase active site, adjacent to the catalytic metal site."}
{"id": "PMID:186262", "title": "Uridine--cytidine kinase from foetal and adult rat liver. Purification and study of some properties.", "content": "Partial purification of uridine--cytidine kinase (EC 2.7.1.48) from foetal rat liver by chromatography on DEAE-cellulose gives two active fractions. The first in order of elution was identified as a form specific for foetal liver. It was purified 300-fold. The second fraction was common to foetal, and adult rat liver and spleen and was purified 20-fold. The foetal fraction of the enzyme was found to be heat-sensitive and protected against inactivation by PO34- anions. The two isolated forms have different apparent Km for uridine, respectively 410 muM for the foetal form and 52 muM for the adult form.", "contents": "Uridine--cytidine kinase from foetal and adult rat liver. Purification and study of some properties. Partial purification of uridine--cytidine kinase (EC 2.7.1.48) from foetal rat liver by chromatography on DEAE-cellulose gives two active fractions. The first in order of elution was identified as a form specific for foetal liver. It was purified 300-fold. The second fraction was common to foetal, and adult rat liver and spleen and was purified 20-fold. The foetal fraction of the enzyme was found to be heat-sensitive and protected against inactivation by PO34- anions. The two isolated forms have different apparent Km for uridine, respectively 410 muM for the foetal form and 52 muM for the adult form."}
{"id": "PMID:186264", "title": "Kinetic transients in the reduction of aldehydes catalysed by liver alcohol dehydrogenase.", "content": "The transient-state kinetics of enzymic reduction of acetaldehyde and benzaldehyde by NADH, catalyzed by horse liver alcohol dehydrogenase, have been examined under single-turnover conditions, obtained by carrying out reactions either with limiting amounts of enzyme in the presence of 20 mM pyrazole or with limiting amounts of substrate. Analysis of the variation with substrate, coenzyme, and enzyme concentrations of amplitudes and time constants for the exponential transients observed at 328 nm and 300 nm shows that the kinetics of enzymic aldehyde reduction are qualitatively and quantitatively consistent with the relationships derived in the preceding paper for an ordered ternary-complex mechanism involving identical and independent catalytic sites. It is concluded that there is no evidence whatsoever for the kinetic significance of a half-of-the-sites reactivity or any other kind of subunit interaction in the liver alcohol dehydrogenase system. The biphasic transients observed at 328 nm for the reduction of aromatic aldehydes such as benzaldehyde are a normal kinetic characteristic of the ordered ternary-complex mechanism, being attributable to accumulation of the ternary enzyme-NAD-product complex when product dissociation from this complex is slow in comparison to its formation by ternary-complex interconversion.", "contents": "Kinetic transients in the reduction of aldehydes catalysed by liver alcohol dehydrogenase. The transient-state kinetics of enzymic reduction of acetaldehyde and benzaldehyde by NADH, catalyzed by horse liver alcohol dehydrogenase, have been examined under single-turnover conditions, obtained by carrying out reactions either with limiting amounts of enzyme in the presence of 20 mM pyrazole or with limiting amounts of substrate. Analysis of the variation with substrate, coenzyme, and enzyme concentrations of amplitudes and time constants for the exponential transients observed at 328 nm and 300 nm shows that the kinetics of enzymic aldehyde reduction are qualitatively and quantitatively consistent with the relationships derived in the preceding paper for an ordered ternary-complex mechanism involving identical and independent catalytic sites. It is concluded that there is no evidence whatsoever for the kinetic significance of a half-of-the-sites reactivity or any other kind of subunit interaction in the liver alcohol dehydrogenase system. The biphasic transients observed at 328 nm for the reduction of aromatic aldehydes such as benzaldehyde are a normal kinetic characteristic of the ordered ternary-complex mechanism, being attributable to accumulation of the ternary enzyme-NAD-product complex when product dissociation from this complex is slow in comparison to its formation by ternary-complex interconversion."}
{"id": "PMID:186265", "title": "An improved procedure for automated Edman degradation used for determination of the N-terminal amino acid sequence of human transcobalamin I and human intrinsic factor.", "content": "An improved procedure for automated Edman degradation is presented. Three programs are described, one with double cleavage and two with single cleavage. The programs presented are characterized by a reversed delivery scheme for buffer and phenyl isothiocyanate, and by reduced cleavage times. The modified procedures applied on automated Edman degradation of the vitamin B12-binding proteins human transcobalamin I and human intrinsic factor, containing approximately 390 and 350 amino residues respectively, gave the following N-terminal amino acid sequences: Human transcobalamin I Glu-Ile-Cys-Glu-Val-Ser-Glu-Glu-Asn-Tyr-Ile-Arg-Leu-Lys-Pro-Leu-Leu-Asn-Thr-Met-Ile-Gln-Ser-Asn-Tyr-Asn-?-Gly- Human intrinsic factor Ser-Thr-Gln-Thr-Gln-Ser-Ser-Cys-Ser-Val-Pro-Ser-Ala-Gln-Glu-Pro-Leu-Val-Asn-Gly-Ile-Gln-?-Leu-Met-Glu-Thr- The background accumulation seems to be related not only to the length of the polypeptide chain being degraded, but also to the content of serine (and possibly threonine). A possible N leads to O acyl shift during the cleavage is a tentative explanation. The programs here represented lead to a significant reduction in background compared to conventional programs and allowed considerable prolongation of the degradations.", "contents": "An improved procedure for automated Edman degradation used for determination of the N-terminal amino acid sequence of human transcobalamin I and human intrinsic factor. An improved procedure for automated Edman degradation is presented. Three programs are described, one with double cleavage and two with single cleavage. The programs presented are characterized by a reversed delivery scheme for buffer and phenyl isothiocyanate, and by reduced cleavage times. The modified procedures applied on automated Edman degradation of the vitamin B12-binding proteins human transcobalamin I and human intrinsic factor, containing approximately 390 and 350 amino residues respectively, gave the following N-terminal amino acid sequences: Human transcobalamin I Glu-Ile-Cys-Glu-Val-Ser-Glu-Glu-Asn-Tyr-Ile-Arg-Leu-Lys-Pro-Leu-Leu-Asn-Thr-Met-Ile-Gln-Ser-Asn-Tyr-Asn-?-Gly- Human intrinsic factor Ser-Thr-Gln-Thr-Gln-Ser-Ser-Cys-Ser-Val-Pro-Ser-Ala-Gln-Glu-Pro-Leu-Val-Asn-Gly-Ile-Gln-?-Leu-Met-Glu-Thr- The background accumulation seems to be related not only to the length of the polypeptide chain being degraded, but also to the content of serine (and possibly threonine). A possible N leads to O acyl shift during the cleavage is a tentative explanation. The programs here represented lead to a significant reduction in background compared to conventional programs and allowed considerable prolongation of the degradations."}
{"id": "PMID:186266", "title": "Effect of cerebral injury on cerebrospinal fluid cyclic AMP concentration.", "content": "Cerbrospinal fluid (CSF) cyclic adenosine-3', 5'-monophosphate (cAMP) was measured in rabbits after experimental brain injury as well as in patients with cerebral contusion and cerebral concussion. In rabbits a marked elevation lasting for two weeks was observed. From the third week onwards after the injury the CSF cAMP concentration was lower than the basal level before the injury. Dexamethasone partly inhibited the elevation. Ethanol treatment decreased the CSF cAMP values. In man, the CSF cAMP concentration was significantly higher in patients with cerebral contusion than in those with cerebral concussion. Also in the latter group the cAMP values were higher than in control patients. Due to the clear differences between the various groups, measurement of cAMP concentration in CSF might have diagnostic value in evaluation of the severity of cerebral lesion in the acute phase. Also the activities of some enzymes were measured, and the results were parallel with cAMP changes but less striking.", "contents": "Effect of cerebral injury on cerebrospinal fluid cyclic AMP concentration. Cerbrospinal fluid (CSF) cyclic adenosine-3', 5'-monophosphate (cAMP) was measured in rabbits after experimental brain injury as well as in patients with cerebral contusion and cerebral concussion. In rabbits a marked elevation lasting for two weeks was observed. From the third week onwards after the injury the CSF cAMP concentration was lower than the basal level before the injury. Dexamethasone partly inhibited the elevation. Ethanol treatment decreased the CSF cAMP values. In man, the CSF cAMP concentration was significantly higher in patients with cerebral contusion than in those with cerebral concussion. Also in the latter group the cAMP values were higher than in control patients. Due to the clear differences between the various groups, measurement of cAMP concentration in CSF might have diagnostic value in evaluation of the severity of cerebral lesion in the acute phase. Also the activities of some enzymes were measured, and the results were parallel with cAMP changes but less striking."}
{"id": "PMID:186267", "title": "Is insomnia a disease of slow-wave sleep?", "content": "The aim of this paper is to examine if a disturbance of slow-wave sleep may partly account for the imbalance between waking and sleep observed in insomnia. 40 normal subjects and 40 insomniacs were recorded in the laboratory. No direct interregulation appeared between total sleep and REM sleep on one hand, and between slow-wave sleep and REM sleep on the other. Slow-wave sleep, however, was linked to the waking-sleep imbalance, as low values of stages 3 and 4 were statistically associated with low total sleep duration. The reduction of slow-wave sleep could not merely be attributed to an increased pressure of wakefulness. Our results indicate that it represents probably a disturbance in itself, perhaps related in some cases to a precocious senescence of sleep, but do not account alone for all sleep disturbances.", "contents": "Is insomnia a disease of slow-wave sleep? The aim of this paper is to examine if a disturbance of slow-wave sleep may partly account for the imbalance between waking and sleep observed in insomnia. 40 normal subjects and 40 insomniacs were recorded in the laboratory. No direct interregulation appeared between total sleep and REM sleep on one hand, and between slow-wave sleep and REM sleep on the other. Slow-wave sleep, however, was linked to the waking-sleep imbalance, as low values of stages 3 and 4 were statistically associated with low total sleep duration. The reduction of slow-wave sleep could not merely be attributed to an increased pressure of wakefulness. Our results indicate that it represents probably a disturbance in itself, perhaps related in some cases to a precocious senescence of sleep, but do not account alone for all sleep disturbances."}
{"id": "PMID:186270", "title": "Stimulation of lymphocytes by allogeneic lymphocytes and lymphoblasts in the presence of anti-HLA antisera.", "content": "Anti-HLA alloantisera inhibit mixed lymphocyte responses in which normal lymphocytes are used as stimulator cells. These same antisera are unable to inhibit lymphocyte proliferative responses stimulated by lymphoblastoid cells from cultured lymphoid cell lines. They also fail to inhibit either the generation of cytotoxic effector cells by lymphoblastoid cells or lymphocyte-mediated cytotoxicity against the lymphoblasts. Although the number of HLA antigens on the surface of lymphoblasts is reported to be greater than on normal lymphocytes, the failure of alloantisera to inhibit lymphoblast-induced responses in vitro does not appear to be due to insufficient amounts of antiserum to react with the antigenic sites. Rather, the data are interpreted to suggest that antigens which are not HLA and are not closely associated with HLA on the lymphocyte membrane are responsible for the stimulation of allogeneic lymphocytes by lymphoblastoid cells. Although lymphoid cell lines are known to contain the genome of the Epstein-Barr virus, antisera against products of the viral genome fail to inhibit proliferative responses to lymphoblastoid cells, suggesting that these antigens do not directly participate in lymphocyte activation.", "contents": "Stimulation of lymphocytes by allogeneic lymphocytes and lymphoblasts in the presence of anti-HLA antisera. Anti-HLA alloantisera inhibit mixed lymphocyte responses in which normal lymphocytes are used as stimulator cells. These same antisera are unable to inhibit lymphocyte proliferative responses stimulated by lymphoblastoid cells from cultured lymphoid cell lines. They also fail to inhibit either the generation of cytotoxic effector cells by lymphoblastoid cells or lymphocyte-mediated cytotoxicity against the lymphoblasts. Although the number of HLA antigens on the surface of lymphoblasts is reported to be greater than on normal lymphocytes, the failure of alloantisera to inhibit lymphoblast-induced responses in vitro does not appear to be due to insufficient amounts of antiserum to react with the antigenic sites. Rather, the data are interpreted to suggest that antigens which are not HLA and are not closely associated with HLA on the lymphocyte membrane are responsible for the stimulation of allogeneic lymphocytes by lymphoblastoid cells. Although lymphoid cell lines are known to contain the genome of the Epstein-Barr virus, antisera against products of the viral genome fail to inhibit proliferative responses to lymphoblastoid cells, suggesting that these antigens do not directly participate in lymphocyte activation."}
{"id": "PMID:186271", "title": "An ultrastructural study of two different responses of mouse mast cells to transplantation antibodies directed against the same transplantation antigens.", "content": "The present paper describes an ultrastructural study of two different kinds of behavior of mouse mast cells during two immunological reactions induced by transplantation antibodies: the direct allogeneic anaphylactic degranulation and the serocytotoxicity. In both situations, the same alloantigens, born by the mast cells themselves, are the targets of the reaction, but the first one is mediated by anaphylactic alloantibodies whereas the second one is mediated by cytotoxic alloantibodies in the presence of complement. The comparison of the ultrastructural aspects of the cells in these two systems demonstrated that mast cells can behave in two different ways depending on the nature of the immunological agents utilized. First, a physiological degranulation process with active granule expulsion was observed. This process was shown to be identical to the one induced in classical in vitro anaphylaxis or by histamine releasers such as compound 48/80. A second type of behavior was a lethal, complement-dependent, cell lysis without active granule expulsion.", "contents": "An ultrastructural study of two different responses of mouse mast cells to transplantation antibodies directed against the same transplantation antigens. The present paper describes an ultrastructural study of two different kinds of behavior of mouse mast cells during two immunological reactions induced by transplantation antibodies: the direct allogeneic anaphylactic degranulation and the serocytotoxicity. In both situations, the same alloantigens, born by the mast cells themselves, are the targets of the reaction, but the first one is mediated by anaphylactic alloantibodies whereas the second one is mediated by cytotoxic alloantibodies in the presence of complement. The comparison of the ultrastructural aspects of the cells in these two systems demonstrated that mast cells can behave in two different ways depending on the nature of the immunological agents utilized. First, a physiological degranulation process with active granule expulsion was observed. This process was shown to be identical to the one induced in classical in vitro anaphylaxis or by histamine releasers such as compound 48/80. A second type of behavior was a lethal, complement-dependent, cell lysis without active granule expulsion."}
{"id": "PMID:186272", "title": "Renal adenylate cyclase-effects of diuretics.", "content": "The in vitro effect of various diuretics on rat kidney adenylate cyclase was investigated in crude homogenates of the cortex, the outer and inner medulla. 10-3 M furosemide inhibited adenylate cyclase by 40% in the cortex, by 16% in the outer medulla and by 43% in the inner medulla. 10-3 M ethacrynic acid inhibited adenylate cyclase activity by 65% in the cortex, 59% in the outer medulla and by 57% in the inner medulla. Amiloride produced no significant inhibition of the adenylate cyclase reaction. In the cortex, furosemide partially inhibited adenylate cyclase under basal, fluoride-stimulated and parathyroid hormone-stimulated conditions. Ethacrynic acid produced a strong inhibition of adenylate cyclase activation by F- and parathyroid hormone. In the inner medulla 10-2 M F- and 1 mU antidiuretic hormone reversed the furosemide effect on adenylate cyclase. Ethacrynic acid produced a strong inhibition of adenylate cyclase in the presence of F- and antidiuretic hormone. It is suggested that inhibition of renal adenylate cyclase might be a possible mode of action of certain diuretics.", "contents": "Renal adenylate cyclase-effects of diuretics. The in vitro effect of various diuretics on rat kidney adenylate cyclase was investigated in crude homogenates of the cortex, the outer and inner medulla. 10-3 M furosemide inhibited adenylate cyclase by 40% in the cortex, by 16% in the outer medulla and by 43% in the inner medulla. 10-3 M ethacrynic acid inhibited adenylate cyclase activity by 65% in the cortex, 59% in the outer medulla and by 57% in the inner medulla. Amiloride produced no significant inhibition of the adenylate cyclase reaction. In the cortex, furosemide partially inhibited adenylate cyclase under basal, fluoride-stimulated and parathyroid hormone-stimulated conditions. Ethacrynic acid produced a strong inhibition of adenylate cyclase activation by F- and parathyroid hormone. In the inner medulla 10-2 M F- and 1 mU antidiuretic hormone reversed the furosemide effect on adenylate cyclase. Ethacrynic acid produced a strong inhibition of adenylate cyclase in the presence of F- and antidiuretic hormone. It is suggested that inhibition of renal adenylate cyclase might be a possible mode of action of certain diuretics."}
{"id": "PMID:186273", "title": "Preferential blockade of presynaptic alpha-adrenoceptors by yohimbine.", "content": "Strips of the rabbit main pulmonary artery were preincubated with 3H-noradrenaline. 3 X 10(-8) -- 10(6) M yohimbine enhanced the overflow of tritium and the smooth muscle contraction induced by transmural sympathetic nerve stimulation. The increase of the stimulation-evoked overflow of tritium was prevented by a high concentration of oxymetazoline. The results indicate that yohimbine is more potent in blocking the presynaptic than the postsynaptic alpha-adrenoceptors of the artery.", "contents": "Preferential blockade of presynaptic alpha-adrenoceptors by yohimbine. Strips of the rabbit main pulmonary artery were preincubated with 3H-noradrenaline. 3 X 10(-8) -- 10(6) M yohimbine enhanced the overflow of tritium and the smooth muscle contraction induced by transmural sympathetic nerve stimulation. The increase of the stimulation-evoked overflow of tritium was prevented by a high concentration of oxymetazoline. The results indicate that yohimbine is more potent in blocking the presynaptic than the postsynaptic alpha-adrenoceptors of the artery."}
{"id": "PMID:186274", "title": "Antagonism by Ca2+ of the inhibitory action of PGE1 on the electrically induced vasoconstriction in the rabbit ear artery.", "content": "The inhibitory action of PGE1 on vasoconstrictor responses to nerve stimulation of isolated ear arteries of rabbits was studied in the presence of 1.0 to 7.5 mM external calcium concentration. Raising the [Ca]0 in the medium increased the electrically induced vasoconstriction and antagonized the inhibitory effect of PGE1 on constrictor responses. This antagonism is probably due to an interaction between Ca2+ and PGE1 in the sympathetic nerves to the vessel.", "contents": "Antagonism by Ca2+ of the inhibitory action of PGE1 on the electrically induced vasoconstriction in the rabbit ear artery. The inhibitory action of PGE1 on vasoconstrictor responses to nerve stimulation of isolated ear arteries of rabbits was studied in the presence of 1.0 to 7.5 mM external calcium concentration. Raising the [Ca]0 in the medium increased the electrically induced vasoconstriction and antagonized the inhibitory effect of PGE1 on constrictor responses. This antagonism is probably due to an interaction between Ca2+ and PGE1 in the sympathetic nerves to the vessel."}
{"id": "PMID:186275", "title": "Inhibition by alpha- and beta-adrenoceptors of the twitch response to transmural stimulation in the guinea-pig vas deferens.", "content": "Noradrenaline as well as the indirectly acting amines tyramine and phenethylamine either enhance or inhibit the twitch response of the transmurally stimulated, isolated guine-pig vas deferens, thus partly confirming previous reports. In both cases enhancement is annulled by alpha-adrenoceptor blockers. The twitch inhibition caused by noradrenaline is abolished by alpha- + beta2-adrenoceptor blockers, but not by either blocker alone. The inhibition caused by the indirectly acting amines is largely abolished by alpha-adrenoceptor blockers. Clonidine strongly inhibits the twitch. This effect if promptly removed by phentolamine. After blockade of the neurally induced twitch by tetrodotoxin, noradrenaline and the indirectly acting amines have no effect or slightly enhance the twitch elicited by transmural stimulation of the smooth muscle. It is concluded that exogenous noradrenaline acts on postjunctional stimulatory alpha-adrenoceptors and on inhibitory alpha- and beta2-adrenoceptors, which are presumably prejunctional. In the unstimulated preparation contracted by acetylcholine, noradrenaline causes further contraction which is changed into relaxation after phentolamine. This relaxation is abolished by butoxamine, suggesting that noradrenaline may also act on inhibitory postjunctional beta2-adrenoceptors. The twitch-inhibiting effect of endogenous noradrenaline, released by nerve stimulation or by indirectly acting amines, appears to be primarily mediated by prejunctional alpha-adrenoceptors.", "contents": "Inhibition by alpha- and beta-adrenoceptors of the twitch response to transmural stimulation in the guinea-pig vas deferens. Noradrenaline as well as the indirectly acting amines tyramine and phenethylamine either enhance or inhibit the twitch response of the transmurally stimulated, isolated guine-pig vas deferens, thus partly confirming previous reports. In both cases enhancement is annulled by alpha-adrenoceptor blockers. The twitch inhibition caused by noradrenaline is abolished by alpha- + beta2-adrenoceptor blockers, but not by either blocker alone. The inhibition caused by the indirectly acting amines is largely abolished by alpha-adrenoceptor blockers. Clonidine strongly inhibits the twitch. This effect if promptly removed by phentolamine. After blockade of the neurally induced twitch by tetrodotoxin, noradrenaline and the indirectly acting amines have no effect or slightly enhance the twitch elicited by transmural stimulation of the smooth muscle. It is concluded that exogenous noradrenaline acts on postjunctional stimulatory alpha-adrenoceptors and on inhibitory alpha- and beta2-adrenoceptors, which are presumably prejunctional. In the unstimulated preparation contracted by acetylcholine, noradrenaline causes further contraction which is changed into relaxation after phentolamine. This relaxation is abolished by butoxamine, suggesting that noradrenaline may also act on inhibitory postjunctional beta2-adrenoceptors. The twitch-inhibiting effect of endogenous noradrenaline, released by nerve stimulation or by indirectly acting amines, appears to be primarily mediated by prejunctional alpha-adrenoceptors."}
{"id": "PMID:186276", "title": "Effect of presynaptic alpha-adrenoceptor blockade on responses to cardiac nerve stimulation in anesthetized dogs.", "content": "Phentolamine caused significant potentiation of chronotropic responses to cardioaccelerator nerve stimulation (CANS) in pentobarbital-anesthetized dogs without impairing neuronal reuptake of norepinephrine. In a separate group of dogs, desipramine produced slight augmentation of CANS responses which were potentiated further by phentolamine administration. These results provide support for the hypothesis that presynaptic alpha-adrenergic receptors play an inhibitory role in sympathetic neurotransmission and demonstrate that this mechanism is also functioning during stimulation of the cardioaccelerator nerve in pentobarbital-anesthetized dogs.", "contents": "Effect of presynaptic alpha-adrenoceptor blockade on responses to cardiac nerve stimulation in anesthetized dogs. Phentolamine caused significant potentiation of chronotropic responses to cardioaccelerator nerve stimulation (CANS) in pentobarbital-anesthetized dogs without impairing neuronal reuptake of norepinephrine. In a separate group of dogs, desipramine produced slight augmentation of CANS responses which were potentiated further by phentolamine administration. These results provide support for the hypothesis that presynaptic alpha-adrenergic receptors play an inhibitory role in sympathetic neurotransmission and demonstrate that this mechanism is also functioning during stimulation of the cardioaccelerator nerve in pentobarbital-anesthetized dogs."}
{"id": "PMID:186277", "title": "Variations in the number of uterine angiotensin receptors following changes in plasma angiotensin levels.", "content": "3H-labelled angiotensin II binding to receptor sites was studied in plasma membranes isolated from myometrial homogenates of uterine horns. Removal of the kidneys, which results in the disappearance of plasma angiotensin II, was followed 19 h after nephrectomy by an increase in the number of uterine receptor sites without significant variation in the apparent dissociation constant. Acute pressor i.v. injection of angiotensin II into nephrectomized rats immediately before removing uteri, did not affect the number of uterine angiotensin receptors, whereas long-lasting angiotensin infusion did reduce the number of receptors. These changes cannot be accounted for by variations in the occupancy of receptor sites. These results demonstrate that the number of angiotensin receptors, at least in uterine contractile cells, is affected by chronic variations of endogenous angiotensin levels. The relation between the specific supersensitivity to angiotensin II observed in uteri from nephrectomized rats and the variations at the receptor level is discussed.", "contents": "Variations in the number of uterine angiotensin receptors following changes in plasma angiotensin levels. 3H-labelled angiotensin II binding to receptor sites was studied in plasma membranes isolated from myometrial homogenates of uterine horns. Removal of the kidneys, which results in the disappearance of plasma angiotensin II, was followed 19 h after nephrectomy by an increase in the number of uterine receptor sites without significant variation in the apparent dissociation constant. Acute pressor i.v. injection of angiotensin II into nephrectomized rats immediately before removing uteri, did not affect the number of uterine angiotensin receptors, whereas long-lasting angiotensin infusion did reduce the number of receptors. These changes cannot be accounted for by variations in the occupancy of receptor sites. These results demonstrate that the number of angiotensin receptors, at least in uterine contractile cells, is affected by chronic variations of endogenous angiotensin levels. The relation between the specific supersensitivity to angiotensin II observed in uteri from nephrectomized rats and the variations at the receptor level is discussed."}
{"id": "PMID:186278", "title": "Neuromuscular blocking action of cadmium and manganese in isolated frog striated muscles.", "content": "In isolated frog sciatic nerve--gastrocnemius muscle preparations, exposure for 60 min to Cd2+ (0.1-2 mM) caused a marked attenuation of the twitch tension developed by stimulation of nerves but no or only a slight inhibition of the tension produced by direct stimulation at maximum twitch height. The inhibitory effect was partially reversed by 1 mM cysteine. In frog sartorius muscles, the addition of Cd2+ (0.1 mM) alos abolished the end-plate potential evoked by nerve stimulation but did not suppress potential changes induced by iontophoretically applied acetylcholine. The addition of Mn2+ (2 and 5 mM) attenuated the response of muscles to both direct and indirect stimulation; a greater attenuation of the latter was observed. The inhibition was not reserved by cysteine but was partially reversed by excess Ca2+. Contractile responses of frog rectus abdominis muscles to acetylcholine were not significantly affected by Cd2+ and Mn2+ but were attenuated by d-tubocurarine in a dose-dependent manner. Impulse conduction along sciatic nerves was not impaired by Cd2+ and Mn2+ but was by procaine. It appears that Cd2+ interferes with the release of acetylcholine from motor nerve terminals by reducing the transmembrane influxes of Ca2+, the influx possibly relating to SH groups of membrane constituents.", "contents": "Neuromuscular blocking action of cadmium and manganese in isolated frog striated muscles. In isolated frog sciatic nerve--gastrocnemius muscle preparations, exposure for 60 min to Cd2+ (0.1-2 mM) caused a marked attenuation of the twitch tension developed by stimulation of nerves but no or only a slight inhibition of the tension produced by direct stimulation at maximum twitch height. The inhibitory effect was partially reversed by 1 mM cysteine. In frog sartorius muscles, the addition of Cd2+ (0.1 mM) alos abolished the end-plate potential evoked by nerve stimulation but did not suppress potential changes induced by iontophoretically applied acetylcholine. The addition of Mn2+ (2 and 5 mM) attenuated the response of muscles to both direct and indirect stimulation; a greater attenuation of the latter was observed. The inhibition was not reserved by cysteine but was partially reversed by excess Ca2+. Contractile responses of frog rectus abdominis muscles to acetylcholine were not significantly affected by Cd2+ and Mn2+ but were attenuated by d-tubocurarine in a dose-dependent manner. Impulse conduction along sciatic nerves was not impaired by Cd2+ and Mn2+ but was by procaine. It appears that Cd2+ interferes with the release of acetylcholine from motor nerve terminals by reducing the transmembrane influxes of Ca2+, the influx possibly relating to SH groups of membrane constituents."}
{"id": "PMID:186279", "title": "Selective activation of nicotinic and muscarinic transmission in cardiac sympathetic ganglion of the dog.", "content": "The myocardial contractile responses to electrical stimulation of different segments of the thoracic sympathetic trunk in the pentobarbital-anesthetized dog were studied. Electrical stimulation of the sympathetic trunk between the second and third thoracic ramus and caudal limb of the ansa subclavia elicited myocardial contractile responses which were not completely antagonized by the ganglionic blocking agent chlorisondamine. Atropine in addition to chlone had no effect. When the sympathetic trunk between the third and fourth ramus was electrically stimulated, the response was partially antagonized by atropine as well as by chlorisondamine alone. From these results, it is suggested that impulses travelling via the third thoracic ramus or above it mediate myocardial contractile responses in which the nicotinic type response predominates whereaas impulses travelling via the fourth thoracic ramus or below it mediate myocardial contractile responses in which the muscarinic type predominates. additionally, evidence presented indicates that a major proportion of both nicotinic and muscarinic receptors mediating myocardial contractile changes are located in the caudal cervical ganglion rather than the stellate ganglion of the dog.", "contents": "Selective activation of nicotinic and muscarinic transmission in cardiac sympathetic ganglion of the dog. The myocardial contractile responses to electrical stimulation of different segments of the thoracic sympathetic trunk in the pentobarbital-anesthetized dog were studied. Electrical stimulation of the sympathetic trunk between the second and third thoracic ramus and caudal limb of the ansa subclavia elicited myocardial contractile responses which were not completely antagonized by the ganglionic blocking agent chlorisondamine. Atropine in addition to chlone had no effect. When the sympathetic trunk between the third and fourth ramus was electrically stimulated, the response was partially antagonized by atropine as well as by chlorisondamine alone. From these results, it is suggested that impulses travelling via the third thoracic ramus or above it mediate myocardial contractile responses in which the nicotinic type response predominates whereaas impulses travelling via the fourth thoracic ramus or below it mediate myocardial contractile responses in which the muscarinic type predominates. additionally, evidence presented indicates that a major proportion of both nicotinic and muscarinic receptors mediating myocardial contractile changes are located in the caudal cervical ganglion rather than the stellate ganglion of the dog."}
{"id": "PMID:186280", "title": "In vivo effects of some tertiary alkylaminoethyl esters with choline acetyltransferase inhibitory properties.", "content": "The tertiary nitrogen derivatives of two choline esters, chloroacetylcholine and acrylcholine, known to inhibit choline acetyltransferase (ChAc) in vitro, were tested for their effects in the whole animal, including peripheral and central cholinergic systems. These esters are N,N-dimethylaminoethyl chloroacetate (Cl-DMA) and N,N-dimethylaminoethyl acrylate (acryl-DMA). The peripheral preparations studied included a neuromuscular junction, a sympathetic ganglion and a postganglionic parasympathetic exocrine preparation. Both Cl-DMA and acryl-DMA blocked responses in these preparations when injected intravenously. The LD50 values for Cl-DMA and acryl-DMA were 640 mg/kg and 183 mg/kg, respectively. Cl-DMA and acryl-DMA were also able to inhibit brain ChAc when injected intravenously by 32% and 18.5%, respectively. The brain levels of acetylcholine (ACh) were significantly reduced by about 25% with Cl-DMA but not significantly with acryl-DMA when the animals were forced to exercise after injection. It is obvious that ChAc inhibition is not effective in decreasing ACh levels significantly under normal conditions.", "contents": "In vivo effects of some tertiary alkylaminoethyl esters with choline acetyltransferase inhibitory properties. The tertiary nitrogen derivatives of two choline esters, chloroacetylcholine and acrylcholine, known to inhibit choline acetyltransferase (ChAc) in vitro, were tested for their effects in the whole animal, including peripheral and central cholinergic systems. These esters are N,N-dimethylaminoethyl chloroacetate (Cl-DMA) and N,N-dimethylaminoethyl acrylate (acryl-DMA). The peripheral preparations studied included a neuromuscular junction, a sympathetic ganglion and a postganglionic parasympathetic exocrine preparation. Both Cl-DMA and acryl-DMA blocked responses in these preparations when injected intravenously. The LD50 values for Cl-DMA and acryl-DMA were 640 mg/kg and 183 mg/kg, respectively. Cl-DMA and acryl-DMA were also able to inhibit brain ChAc when injected intravenously by 32% and 18.5%, respectively. The brain levels of acetylcholine (ACh) were significantly reduced by about 25% with Cl-DMA but not significantly with acryl-DMA when the animals were forced to exercise after injection. It is obvious that ChAc inhibition is not effective in decreasing ACh levels significantly under normal conditions."}
{"id": "PMID:186281", "title": "Possible role of prostaglandin E1 on adrenergic neurotransmission in the guinea-pig taenia coli.", "content": "The effects of prostaglandin (PG) E1 were investigated on the responses to adrenergic and non-adrenergic inhibitory nerve stimulation using the perivascular nerve-taenia preparation of the guinea pig. PGE1 caused a rapid and sustained contraction and markedly inhibited the response to adrenergic but not to non-adrenergic inhibitory nerve stimulation. It was also observed that PGE1 had some desensitizing action to exogenous noradrenaline on the postjunctional site. Although indomethacin decreased the tone of the preparation, it potentiated the response to adrenergic nerve stimulation without any effects on the response to non-adrenergic inhibitory nerve stimulation. From these observations, it was concluded that endogenous PGE1 may also play a regulatory role in adrenergic inhibitory neurotransmission, mainly by inhibitory action on noradrenaline release and partly by a similar action on the postjunctional site.", "contents": "Possible role of prostaglandin E1 on adrenergic neurotransmission in the guinea-pig taenia coli. The effects of prostaglandin (PG) E1 were investigated on the responses to adrenergic and non-adrenergic inhibitory nerve stimulation using the perivascular nerve-taenia preparation of the guinea pig. PGE1 caused a rapid and sustained contraction and markedly inhibited the response to adrenergic but not to non-adrenergic inhibitory nerve stimulation. It was also observed that PGE1 had some desensitizing action to exogenous noradrenaline on the postjunctional site. Although indomethacin decreased the tone of the preparation, it potentiated the response to adrenergic nerve stimulation without any effects on the response to non-adrenergic inhibitory nerve stimulation. From these observations, it was concluded that endogenous PGE1 may also play a regulatory role in adrenergic inhibitory neurotransmission, mainly by inhibitory action on noradrenaline release and partly by a similar action on the postjunctional site."}
{"id": "PMID:186282", "title": "Effects of hydralazines on canine muscarinic ganglion transmission.", "content": "The effects of hydralazine, dihydralazine and 4-propyl-1-hydrazinophthalazine (4-propylhydralazine) were investigated on reflex pressor responses to increased intracranial fluid pressure (IIP) during occlusion of the abdominal aorta and the vena cava (MVO). It has been shown that application of MVO, caudal to the renal arteries, produces two independent vascular zones in the animal (Steinberg and Hilton, 1966a). Increasing intracranial fluid pressure during MVO elicits a reflex pressor response which consists of two components. One component is blocked by the nicotinic ganglionic blocking agent, chlorisondamine, and the other component is blocked by small doses of atropine. It was found that hydralazine and dihydralazine were effective in blocking residual pressor responses following partial blockade of reflex pressor responses to IIP with chlorisondamine. 4-Propylhydralazine, which is chemically similar to hydralazine and dihydralazine, was less active in inhibiting the residual pressor responses. It is suggested that hydralazine may act in part by interfering with muscarinic ganglionic transmission.", "contents": "Effects of hydralazines on canine muscarinic ganglion transmission. The effects of hydralazine, dihydralazine and 4-propyl-1-hydrazinophthalazine (4-propylhydralazine) were investigated on reflex pressor responses to increased intracranial fluid pressure (IIP) during occlusion of the abdominal aorta and the vena cava (MVO). It has been shown that application of MVO, caudal to the renal arteries, produces two independent vascular zones in the animal (Steinberg and Hilton, 1966a). Increasing intracranial fluid pressure during MVO elicits a reflex pressor response which consists of two components. One component is blocked by the nicotinic ganglionic blocking agent, chlorisondamine, and the other component is blocked by small doses of atropine. It was found that hydralazine and dihydralazine were effective in blocking residual pressor responses following partial blockade of reflex pressor responses to IIP with chlorisondamine. 4-Propylhydralazine, which is chemically similar to hydralazine and dihydralazine, was less active in inhibiting the residual pressor responses. It is suggested that hydralazine may act in part by interfering with muscarinic ganglionic transmission."}
{"id": "PMID:186283", "title": "A method for site selectivity analysis applied to opiate receptors.", "content": "A method has been developed to determine whether or not a receptor system consists of several sites with different binding specificity. Several radioactive indicator drugs are used in solutions of identical chemical composition. Homogeneity of the receptor system is tested graphically. We have applied the method to a study of opiate receptors. It appeared that there were at least two different binding sites. Several different competitors with various characteristics have been tested against three indicator solutions with radioactive dihydromorphine, naloxone and naltrexone respectively. Three different classes of opiates were observed in the system, morphine-like, naltrexone-like and an intermediate group. A morphine-like substance shows high selectivity for one of the sites while naltrexone-like compounds show practically no discrimination between the sites and a group of partial agonists such as nalorphine is intermediate.", "contents": "A method for site selectivity analysis applied to opiate receptors. A method has been developed to determine whether or not a receptor system consists of several sites with different binding specificity. Several radioactive indicator drugs are used in solutions of identical chemical composition. Homogeneity of the receptor system is tested graphically. We have applied the method to a study of opiate receptors. It appeared that there were at least two different binding sites. Several different competitors with various characteristics have been tested against three indicator solutions with radioactive dihydromorphine, naloxone and naltrexone respectively. Three different classes of opiates were observed in the system, morphine-like, naltrexone-like and an intermediate group. A morphine-like substance shows high selectivity for one of the sites while naltrexone-like compounds show practically no discrimination between the sites and a group of partial agonists such as nalorphine is intermediate."}
{"id": "PMID:186284", "title": "Stimulated formation of cyclic AMP in different areas of chick brain.", "content": "Marked accumulation of cerebral cyclic AMP was induced in the chick by the i.v. administration of isoprenaline or histamine of by decapitation. These responses were examined in various cerebral regions and compared to the responses produced in vitro when maximal concentrations of isoprenaline, histamine or adenosine were added to appropriate brain slices. Histamine only markedly stimulated cyclic AMP formation in the cerebral hemispheres. Isoprenaline was equally potent in the cerebellum and the cerebral hemispheres though the medulla-diencephalon and optic lobes were less responsive. There was a lack of correlation between the effects of decapitation in vivo and the responses to adenosine in vitro. Similar accumulations of cyclic AMP were produced by decapitation in the cerebral hemispheres and cerebellum though adenosine was much more effective on cerebellar slices in vitro. The topographical distribution of catecholamine and histamine sensitive cyclic AMP forming sites do not correlate with endogenous levels of noradrenaline or histamine in chick brain and possible interpretations are discussed.", "contents": "Stimulated formation of cyclic AMP in different areas of chick brain. Marked accumulation of cerebral cyclic AMP was induced in the chick by the i.v. administration of isoprenaline or histamine of by decapitation. These responses were examined in various cerebral regions and compared to the responses produced in vitro when maximal concentrations of isoprenaline, histamine or adenosine were added to appropriate brain slices. Histamine only markedly stimulated cyclic AMP formation in the cerebral hemispheres. Isoprenaline was equally potent in the cerebellum and the cerebral hemispheres though the medulla-diencephalon and optic lobes were less responsive. There was a lack of correlation between the effects of decapitation in vivo and the responses to adenosine in vitro. Similar accumulations of cyclic AMP were produced by decapitation in the cerebral hemispheres and cerebellum though adenosine was much more effective on cerebellar slices in vitro. The topographical distribution of catecholamine and histamine sensitive cyclic AMP forming sites do not correlate with endogenous levels of noradrenaline or histamine in chick brain and possible interpretations are discussed."}
{"id": "PMID:186285", "title": "Calcium uptake by myometrial membranes: effect of A 23187, a calcium ionophore.", "content": "A subcellular fraction, relatively enriched with plasma membranes, showed an ATP-dependent Ca2+ uptake. The addition of a Ca2+. Other drugs (angiotensin, prostaglandin F2alpha, 5-hydroxytryptamine and cyclic nucleotides) had negligible effects on Ca2+ transport. The preparation appears to transport Ca2+, although binding is negligible.", "contents": "Calcium uptake by myometrial membranes: effect of A 23187, a calcium ionophore. A subcellular fraction, relatively enriched with plasma membranes, showed an ATP-dependent Ca2+ uptake. The addition of a Ca2+. Other drugs (angiotensin, prostaglandin F2alpha, 5-hydroxytryptamine and cyclic nucleotides) had negligible effects on Ca2+ transport. The preparation appears to transport Ca2+, although binding is negligible."}
{"id": "PMID:186293", "title": "Weakening of genetic resistance. II. The effect of injection of the macrophage toxic agents silica and carragheenan and the cytostatic drugs cyclophosphamide, busulphan and vinblastin.", "content": "Silica (4 mg/i.v.) and Carragheenan (20 mg/i.p.) were shown to be capable of weakening hybrid resistance in the spleen whereas no improved growth was observed in the femoral bone marrow. Histological data did not indicate that the agents in the doses used caused significant macrophage mortality. It was concluded that the weakening effect of the agents was not due to death of the effector cells but possibly to a stimulation of the mononuclear phagocytic system in the spleen. Cyclophosphamide (250 mg/kg) induced a weakening of hybrid resistance which was observed both in the spleen and the femoral bone marrow. Experiments with the alkylating agent Busulphan and with Vinblastin showed that both agents were only capable of inducing a moderate stimulation of growth of the transplant in the spleen. A direct specific influence of cyclophosphamide on the microenvironment was proposed. Xenogeneic resistance was studied by transplantation of rat bone marrow to mice. Silica and cyclophosphamide were shown to be capable of inducing a weakening of the resistance in the spleen. The development of the graft in the femoral bone marrow did not appear to be affected by the administration of silica or cyclophosphamide.", "contents": "Weakening of genetic resistance. II. The effect of injection of the macrophage toxic agents silica and carragheenan and the cytostatic drugs cyclophosphamide, busulphan and vinblastin. Silica (4 mg/i.v.) and Carragheenan (20 mg/i.p.) were shown to be capable of weakening hybrid resistance in the spleen whereas no improved growth was observed in the femoral bone marrow. Histological data did not indicate that the agents in the doses used caused significant macrophage mortality. It was concluded that the weakening effect of the agents was not due to death of the effector cells but possibly to a stimulation of the mononuclear phagocytic system in the spleen. Cyclophosphamide (250 mg/kg) induced a weakening of hybrid resistance which was observed both in the spleen and the femoral bone marrow. Experiments with the alkylating agent Busulphan and with Vinblastin showed that both agents were only capable of inducing a moderate stimulation of growth of the transplant in the spleen. A direct specific influence of cyclophosphamide on the microenvironment was proposed. Xenogeneic resistance was studied by transplantation of rat bone marrow to mice. Silica and cyclophosphamide were shown to be capable of inducing a weakening of the resistance in the spleen. The development of the graft in the femoral bone marrow did not appear to be affected by the administration of silica or cyclophosphamide."}
{"id": "PMID:186294", "title": "Localization of evoked potentials in the digastric, masseteric, supra- and intertrigeminal subnuclei of the cat.", "content": "Extracellular focal potentials were evoked and mapped in the trigeminal motor nucleus and its surrounding borderzone in the cat. Graded electrical stimulation was used for orthodromic and antidromic excitation of the masseteric and digastric motoneurones and for orthodromic stimulation of the lingual and inferior alveolar nerves. The method of referring Horsley Clarke coordinates of microelectrode recording positions to their location of the actual histological section was studied and the total error affecting the method was calculated for the H, AP and L axes. The characteristics and the distribution of the evoked focal potentials were described and related to the histological section from the actual experiment. A phase reversal of the negative focal potential evoked by the lingual and inferior alveolar nerves in the main sensory nucleus and in the intertrigeminal nucleus was observed to indicate the dorso-lateral border of the motor nucleus. Other borders were given by the antidromic potentials evoked in the nucleus. Digastric motoneurones were found medially in the caudal third and ventro-medially in the middle third of the motor nucleus. The masseteric motoneurones were located laterally in the middle and rostral thirds of the nucleus. Potentials evoked in the supratrigeminal and intertrigeminal subnuclei, adjacent to the motor nucleus, were considered and discussed in relation to the available evidence of interneurones subserving trigeminal reflex arcs.", "contents": "Localization of evoked potentials in the digastric, masseteric, supra- and intertrigeminal subnuclei of the cat. Extracellular focal potentials were evoked and mapped in the trigeminal motor nucleus and its surrounding borderzone in the cat. Graded electrical stimulation was used for orthodromic and antidromic excitation of the masseteric and digastric motoneurones and for orthodromic stimulation of the lingual and inferior alveolar nerves. The method of referring Horsley Clarke coordinates of microelectrode recording positions to their location of the actual histological section was studied and the total error affecting the method was calculated for the H, AP and L axes. The characteristics and the distribution of the evoked focal potentials were described and related to the histological section from the actual experiment. A phase reversal of the negative focal potential evoked by the lingual and inferior alveolar nerves in the main sensory nucleus and in the intertrigeminal nucleus was observed to indicate the dorso-lateral border of the motor nucleus. Other borders were given by the antidromic potentials evoked in the nucleus. Digastric motoneurones were found medially in the caudal third and ventro-medially in the middle third of the motor nucleus. The masseteric motoneurones were located laterally in the middle and rostral thirds of the nucleus. Potentials evoked in the supratrigeminal and intertrigeminal subnuclei, adjacent to the motor nucleus, were considered and discussed in relation to the available evidence of interneurones subserving trigeminal reflex arcs."}
{"id": "PMID:186295", "title": "Further evidence for common antigens in intracytoplasmic A particles of mouse mammary tumors and B type virions of murine milk.", "content": "Using the indirect immunofluorescence technique and radioimmunoprecipitation test (RIP test) according to ABELEV and ELGORT (1970) immunological investigations intracytoplasmic A particles isolated from mouse mammary tumors were performed. In order to purify the virus particles sucrose gradients were employed according to TANAKA et al. (1972) and in some details according to SMITH and WIVEL (1973). In immunofluorescence studies on mammary tumor slices a complete cross-reaction between antisera against A particles from mammary tumors and MTV-B particles from mouse milk was observed. Both kinds of antisera reacted in identical fluorescence pattern types with intracytoplasmic A particle clusters and with extracellular accumulations of B type virions, respectively, in tumors of different histological structures. RIP test studies suggest that these cross-reactions are attributed to three common antigens in A and B type viruses. Thus, there does not remain any doubt that intracytoplasmic A particles in murine mammary tumors are MTV-related. All these A particles antigens were identically detected using an antiserum against A particles isolated from mouse leukemia cells (serum kindly provided by Dr. TANAKA). The biological role of intracytoplasmic A particles in mouse tissues is discussed. In contrast to the precursor theory, it is believed that they could represent something like a nonsense way of particle maturation in MTV-infected cells.", "contents": "Further evidence for common antigens in intracytoplasmic A particles of mouse mammary tumors and B type virions of murine milk. Using the indirect immunofluorescence technique and radioimmunoprecipitation test (RIP test) according to ABELEV and ELGORT (1970) immunological investigations intracytoplasmic A particles isolated from mouse mammary tumors were performed. In order to purify the virus particles sucrose gradients were employed according to TANAKA et al. (1972) and in some details according to SMITH and WIVEL (1973). In immunofluorescence studies on mammary tumor slices a complete cross-reaction between antisera against A particles from mammary tumors and MTV-B particles from mouse milk was observed. Both kinds of antisera reacted in identical fluorescence pattern types with intracytoplasmic A particle clusters and with extracellular accumulations of B type virions, respectively, in tumors of different histological structures. RIP test studies suggest that these cross-reactions are attributed to three common antigens in A and B type viruses. Thus, there does not remain any doubt that intracytoplasmic A particles in murine mammary tumors are MTV-related. All these A particles antigens were identically detected using an antiserum against A particles isolated from mouse leukemia cells (serum kindly provided by Dr. TANAKA). The biological role of intracytoplasmic A particles in mouse tissues is discussed. In contrast to the precursor theory, it is believed that they could represent something like a nonsense way of particle maturation in MTV-infected cells."}
{"id": "PMID:186296", "title": "The mannophosphoinositides of Nocardia asteroides.", "content": "The phospholipid of N. asteroides has been investigated. It was found to contain phosphatidyl ethanolamine, cardiolipin, phosphatidyl inositol and a family of mannophosphoinositides. Dimannophosphoinositides with 3 and 4 moles of fatty acid per phosphate residue represented the major glycophospholipids besides small amounts of other more glycosylated mannophosphoinositides.", "contents": "The mannophosphoinositides of Nocardia asteroides. The phospholipid of N. asteroides has been investigated. It was found to contain phosphatidyl ethanolamine, cardiolipin, phosphatidyl inositol and a family of mannophosphoinositides. Dimannophosphoinositides with 3 and 4 moles of fatty acid per phosphate residue represented the major glycophospholipids besides small amounts of other more glycosylated mannophosphoinositides."}
{"id": "PMID:186298", "title": "Adenosine promoted accumulation of adenosine 3',5'-monophosphate in rabbit vagus nerve.", "content": "Desheathed rabbit vagus nerve has been found to form cyclic AMP when incubated with adenosine. This accumulation of cyclic AMP is inhibited by theophylline but not by antiadrenergic agents, anticholinergic agents or local anaesthetics. Depolarizing media are not able to promote cyclic AMP accumulation in this preparation.", "contents": "Adenosine promoted accumulation of adenosine 3',5'-monophosphate in rabbit vagus nerve. Desheathed rabbit vagus nerve has been found to form cyclic AMP when incubated with adenosine. This accumulation of cyclic AMP is inhibited by theophylline but not by antiadrenergic agents, anticholinergic agents or local anaesthetics. Depolarizing media are not able to promote cyclic AMP accumulation in this preparation."}
{"id": "PMID:186299", "title": "Effects of stress and adrenocorticotrophin administration on plasma corticosterone levels at different stages of pregnancy in the mouse.", "content": "Stress or administration of ACTH to pregnant mice gave rise to much higher plasma corticosterone levels in the second half of pregnancy than in the first half, suggesting that there may be increased adrenal sensitivity to ACTH or decreased metabolism of corticosterone during the second half of pregnancy.", "contents": "Effects of stress and adrenocorticotrophin administration on plasma corticosterone levels at different stages of pregnancy in the mouse. Stress or administration of ACTH to pregnant mice gave rise to much higher plasma corticosterone levels in the second half of pregnancy than in the first half, suggesting that there may be increased adrenal sensitivity to ACTH or decreased metabolism of corticosterone during the second half of pregnancy."}
{"id": "PMID:186331", "title": "Some aspects of neurophysiological basis of insecticide action.", "content": "When the insecticide parathion was administered to awake, unrestrained rats with chronically implanted brain electrodes, it was observed that the latency of the averaged flash-evoked potential in the visual cortex and superior colliculus was increased and the amplitude was decreased 2 to 4 hours later with responses returning to pretreatment levels about 8 hours after administration. Similarly, after administration of several dose levels of parathion in the rat, durations of phases of the maximal electroshock seizure (MES) pattern were altered to the greatest extent 4 hours later, but effects disappeared at 24 hours. These effects of parathion on the MES and evoked potentials coincided with a fall in blood and brain acetylcholinesterase (AChe) activities but disappeared after AChe inhibition had reached its peak and stabilized. Brain AChe activities required 2 to 4 weeks for recovery whereas blood AChe activity recovered in 1 week following inhibition by parathion (at least 2 mg/kg body weight). Studies in the monkey demonstrated similar results. Because these measurements of central nervous system function returned to normal despite continued inhibition of AChe activity, the results are interpreted to mean either that adaptation of evoked potentials or MES responses to prolonged AChe inhibition can occur in the rat and monkey after parathion administration or that some of the effects of parathion do not depend on AChe inhibition. Administration of DDT (100 mg/kg by mouth) to awake, unrestrained rats markedly increased the amplitude of spontaneous electrical activity in the cerebellum, whereas there was much less effect on electrical activity recorded simultaneously in the occipital cortex, reticular formation, and medial geniculate body. Similarly, DDT administration had marked effects on the averaged, sound evoked potential recorded in the cerebellum; DDT caused the appearance and increased the amplitude of an early component of this response not usually present during control recordings. Sound-evoked potentials recorded simultaneously from the frontal and occipital cortex and reticular formation were affected less or were decreased in amplitude by administration of DDT.", "contents": "Some aspects of neurophysiological basis of insecticide action. When the insecticide parathion was administered to awake, unrestrained rats with chronically implanted brain electrodes, it was observed that the latency of the averaged flash-evoked potential in the visual cortex and superior colliculus was increased and the amplitude was decreased 2 to 4 hours later with responses returning to pretreatment levels about 8 hours after administration. Similarly, after administration of several dose levels of parathion in the rat, durations of phases of the maximal electroshock seizure (MES) pattern were altered to the greatest extent 4 hours later, but effects disappeared at 24 hours. These effects of parathion on the MES and evoked potentials coincided with a fall in blood and brain acetylcholinesterase (AChe) activities but disappeared after AChe inhibition had reached its peak and stabilized. Brain AChe activities required 2 to 4 weeks for recovery whereas blood AChe activity recovered in 1 week following inhibition by parathion (at least 2 mg/kg body weight). Studies in the monkey demonstrated similar results. Because these measurements of central nervous system function returned to normal despite continued inhibition of AChe activity, the results are interpreted to mean either that adaptation of evoked potentials or MES responses to prolonged AChe inhibition can occur in the rat and monkey after parathion administration or that some of the effects of parathion do not depend on AChe inhibition. Administration of DDT (100 mg/kg by mouth) to awake, unrestrained rats markedly increased the amplitude of spontaneous electrical activity in the cerebellum, whereas there was much less effect on electrical activity recorded simultaneously in the occipital cortex, reticular formation, and medial geniculate body. Similarly, DDT administration had marked effects on the averaged, sound evoked potential recorded in the cerebellum; DDT caused the appearance and increased the amplitude of an early component of this response not usually present during control recordings. Sound-evoked potentials recorded simultaneously from the frontal and occipital cortex and reticular formation were affected less or were decreased in amplitude by administration of DDT."}
{"id": "PMID:186333", "title": "[Effect of acoustic stimulation on lipid metabolism, indices of the blood coagulation system and development of experimental atherosclerosis in rabbits].", "content": "The 14-day sound stimulation of healthy rabbits increases the level of unesterified fatty acids and the blood coagulability. Morphologically the hypertrophy of the heart coronary arteries and necrotic foci in the myocardium are revealed. In rabbits with experimental atherosclerosis subjected to sound stimulation during 14 and 28 days, in spite of a high level of lipids in the blood and hypercoagulatory shifts, the developing conditions aid to resorption of lipids from aortal plagues and coronary arteries. Apart from that, morphological studies reveal hypertrophy and oedema of the vascular wall, necrotic foci, local and diffuse fatty infiltration of the myocardium.", "contents": "[Effect of acoustic stimulation on lipid metabolism, indices of the blood coagulation system and development of experimental atherosclerosis in rabbits]. The 14-day sound stimulation of healthy rabbits increases the level of unesterified fatty acids and the blood coagulability. Morphologically the hypertrophy of the heart coronary arteries and necrotic foci in the myocardium are revealed. In rabbits with experimental atherosclerosis subjected to sound stimulation during 14 and 28 days, in spite of a high level of lipids in the blood and hypercoagulatory shifts, the developing conditions aid to resorption of lipids from aortal plagues and coronary arteries. Apart from that, morphological studies reveal hypertrophy and oedema of the vascular wall, necrotic foci, local and diffuse fatty infiltration of the myocardium."}
{"id": "PMID:186334", "title": "[Effect of catecholamines on sodium resorption and oxygen tension in rat kidneys].", "content": "Functional significance of alpha- and beta-adrenoreceptors for the mechanism of catecholamines effect on sodium reabsorption and oxygen tension in the rat kidney, was studied. Adrenaline inhibited sodium excretion decreasing its filtration in glomeruli and stimulating its reabsorption in tubules. The oxygen tension in these conditions did not change in the renal cortex while oxygenation of the external cortical layer was significantly increased. The blocking agent for alpha-adrenoreceptors phentolamin abolished the inhibiting effect of adrenaline on the glomerular filtration and somewhat decreased the degree of oxygen tension growth in the external cortical layer, leaving the tubular effect unaltered. The blocking agent for beta-adrenoreceptors inderal did not affect the inhibitory action of adrenaline on the glomerular filtration but completely prevented its activating effect on the tubular reabsorption of sodium and on oxygenation of the external cortical layer. A conclusion was drawn that catecholamines stimulation of sodium reabsorption in the rat kidney follows excitation of beta-adrenoreceptors. The increase in oxygen tension in the external cortical layer under effect of catecholamines is supposed to improve energetic supply of the sodium active transport in the ascending portion of the Henle loops.", "contents": "[Effect of catecholamines on sodium resorption and oxygen tension in rat kidneys]. Functional significance of alpha- and beta-adrenoreceptors for the mechanism of catecholamines effect on sodium reabsorption and oxygen tension in the rat kidney, was studied. Adrenaline inhibited sodium excretion decreasing its filtration in glomeruli and stimulating its reabsorption in tubules. The oxygen tension in these conditions did not change in the renal cortex while oxygenation of the external cortical layer was significantly increased. The blocking agent for alpha-adrenoreceptors phentolamin abolished the inhibiting effect of adrenaline on the glomerular filtration and somewhat decreased the degree of oxygen tension growth in the external cortical layer, leaving the tubular effect unaltered. The blocking agent for beta-adrenoreceptors inderal did not affect the inhibitory action of adrenaline on the glomerular filtration but completely prevented its activating effect on the tubular reabsorption of sodium and on oxygenation of the external cortical layer. A conclusion was drawn that catecholamines stimulation of sodium reabsorption in the rat kidney follows excitation of beta-adrenoreceptors. The increase in oxygen tension in the external cortical layer under effect of catecholamines is supposed to improve energetic supply of the sodium active transport in the ascending portion of the Henle loops."}
{"id": "PMID:186335", "title": "Transformation of Chinese hamster embryo cells with an avian sarcoma virus ts mutant.", "content": "Chinese hamster embryo cells were transformed with temperature-sensitive mutant of the Schmidt-Ruppin strain of Rous sarcoma virus-subgroup A (ts NY68S Ra-A). The developed cell line elicited the morphological transformation at a permissive temperature of 35 degrees C, whereas after a shift to a non-permissive temperature of 40 degrees C the cells reverted to a normal phenotype. Tests for the presence of avian sarcoma group-specific antigen showed that the antigen was not expressed both at permissive and non-permissive temperature. However, the transient expression of gs antigen could be achieved by treatment with 5-IUdR only at the permissive temperature. There was a difference in the rate of 14C-2-deoxy-D-glucose uptake between cells cultured at the permissive and non-permissive temperature.", "contents": "Transformation of Chinese hamster embryo cells with an avian sarcoma virus ts mutant. Chinese hamster embryo cells were transformed with temperature-sensitive mutant of the Schmidt-Ruppin strain of Rous sarcoma virus-subgroup A (ts NY68S Ra-A). The developed cell line elicited the morphological transformation at a permissive temperature of 35 degrees C, whereas after a shift to a non-permissive temperature of 40 degrees C the cells reverted to a normal phenotype. Tests for the presence of avian sarcoma group-specific antigen showed that the antigen was not expressed both at permissive and non-permissive temperature. However, the transient expression of gs antigen could be achieved by treatment with 5-IUdR only at the permissive temperature. There was a difference in the rate of 14C-2-deoxy-D-glucose uptake between cells cultured at the permissive and non-permissive temperature."}
{"id": "PMID:186341", "title": "Regulation by glucose and cyclic nucleotides of the glucagon and insulin release induced by amino acids.", "content": "The glucagon and insulin release induced by amino acids was studied in the presence of glucose, dibutyryl cyclic AMP (dbcAMP) or theophylline on the splenic part of the pancreas of new born rats (48 to 64 hours). The results were compared to the literature data. Arginine or a mixture of the three amino acids (A.A.), arginine, lysine or alanine, stimulate glucagon secretion at 1.6 mM glucose. This stimulation is suppressed by 16.7 mM glucose. On the other hand, 16.7 mM glucose potentiates the effect of arginine or of the 3 A.A. on insulin release. At 1.6 mM glucose, theophylline potentiates the effect of 3 A.A. (10 mM each) on glucagon and insulin release : this effect reaches a maximum at 5 mM of theophylline; dbcAMP also potentiates the effect of 3 A.A. on glucagon and insulin release, and the effect of arginine, alanine or lysine on glucagon release. On the beta cell, the lack of potentiation observed between dbcAMP and arginine, lysine or alanine indicates that these A.A. interact positively when mixed together. In the presence of arginine or of the three A.A., the percentage stimulation of glucagon and insulin release depends on the dbcAMP dose and does not vary with the glucose concentration. The increase of glucagon and insulin release observed when the NaCl concentration in the incubation medium decreases cannot account for our results. Cyclic GMP (4 mM) does not modify the glucagon or insulin secretion induced by different concentrations of glucose or by the mixture of A.A. (10 mM each). The stimulating effect of acetylcholine on insulin release would not be related to the cyclic GMP molecule. In conclusion, instead of modifying the specificity of substrate, theophylline or dbcAMP accentuate it: glucose stimulates specifically the beta cell whereas 3 A.A. are more effective on the alpha2 cell than the beta cell. Cyclic AMP suppresses the glucose effect on glucagon release induced by the amino acids. Because of its interaction with glucose and amino acids, cyclic AMP seems to be a very important element in the regulation of the release of these pancreatic hormones.", "contents": "Regulation by glucose and cyclic nucleotides of the glucagon and insulin release induced by amino acids. The glucagon and insulin release induced by amino acids was studied in the presence of glucose, dibutyryl cyclic AMP (dbcAMP) or theophylline on the splenic part of the pancreas of new born rats (48 to 64 hours). The results were compared to the literature data. Arginine or a mixture of the three amino acids (A.A.), arginine, lysine or alanine, stimulate glucagon secretion at 1.6 mM glucose. This stimulation is suppressed by 16.7 mM glucose. On the other hand, 16.7 mM glucose potentiates the effect of arginine or of the 3 A.A. on insulin release. At 1.6 mM glucose, theophylline potentiates the effect of 3 A.A. (10 mM each) on glucagon and insulin release : this effect reaches a maximum at 5 mM of theophylline; dbcAMP also potentiates the effect of 3 A.A. on glucagon and insulin release, and the effect of arginine, alanine or lysine on glucagon release. On the beta cell, the lack of potentiation observed between dbcAMP and arginine, lysine or alanine indicates that these A.A. interact positively when mixed together. In the presence of arginine or of the three A.A., the percentage stimulation of glucagon and insulin release depends on the dbcAMP dose and does not vary with the glucose concentration. The increase of glucagon and insulin release observed when the NaCl concentration in the incubation medium decreases cannot account for our results. Cyclic GMP (4 mM) does not modify the glucagon or insulin secretion induced by different concentrations of glucose or by the mixture of A.A. (10 mM each). The stimulating effect of acetylcholine on insulin release would not be related to the cyclic GMP molecule. In conclusion, instead of modifying the specificity of substrate, theophylline or dbcAMP accentuate it: glucose stimulates specifically the beta cell whereas 3 A.A. are more effective on the alpha2 cell than the beta cell. Cyclic AMP suppresses the glucose effect on glucagon release induced by the amino acids. Because of its interaction with glucose and amino acids, cyclic AMP seems to be a very important element in the regulation of the release of these pancreatic hormones."}
{"id": "PMID:186342", "title": "[Energy metabolism in the perinatal period (author's transl)].", "content": "Neonatal hypoglycemia is of frequent occurrence in fasted newborn babies or animals but the origin of this hypoglycemia is not fully understood. Studies performed in newborn rats have shown that liver glycogenolysis and gluconeogenesis occur immediately after birth and that the increase in the activities of key regulatory enzymes (phosphorylase, glycogen synthetase and phosphoenolpyruvate carboxykinase) results probably from the rise of plasma glucagon and the fall of plasma insulin induced by the \"stress\" of birth. When the liver glycogen stores have been exhausted, i.e. between 6 and 16 hours after birth, a profound hypoglycemia develops in fasting newborn rats. The inability of hepatic gluconeogenesis to produce sufficient glucose to meet the energy requirement of the newborn tissues results from a lack of fat-derived (free fatty acids and ketone bodies) and gluconeogenic (lactate, amino acids) substrates. The stage of appearance and the mechanisms regulating gluconeogenesis in other species including human are discussed.", "contents": "[Energy metabolism in the perinatal period (author's transl)]. Neonatal hypoglycemia is of frequent occurrence in fasted newborn babies or animals but the origin of this hypoglycemia is not fully understood. Studies performed in newborn rats have shown that liver glycogenolysis and gluconeogenesis occur immediately after birth and that the increase in the activities of key regulatory enzymes (phosphorylase, glycogen synthetase and phosphoenolpyruvate carboxykinase) results probably from the rise of plasma glucagon and the fall of plasma insulin induced by the \"stress\" of birth. When the liver glycogen stores have been exhausted, i.e. between 6 and 16 hours after birth, a profound hypoglycemia develops in fasting newborn rats. The inability of hepatic gluconeogenesis to produce sufficient glucose to meet the energy requirement of the newborn tissues results from a lack of fat-derived (free fatty acids and ketone bodies) and gluconeogenic (lactate, amino acids) substrates. The stage of appearance and the mechanisms regulating gluconeogenesis in other species including human are discussed."}
{"id": "PMID:186345", "title": "Measurement and partial characterization of immunoreactive glucagon in gastrointestinal tissues of dogs.", "content": "We have reported previously that increasing amounts of immunoreactive glucagon (IRG), measured by four specific antisera, appeared in plasma of depancreatized insulin-deficient dogs. It was therefore concluded that pancreatectomy was not accompanied by glucagon deficiency in the dog, but instead excessive amounts of extrapancreatic IRG could contribute to the diabetic syndrome. In order to locate the source of extrapancreatic glucagon, tissue extracts were assayed with anti-glucagon sera 30-K and K-44, which cross-react minimally with crude gut extracts. IRG was detected in all gastrointestinal tissues and in the salivary glands, but not in extracts of liver, kidney, brain, heart atrium, and adenohypophysis. Immunologic dilution curves of extracts from all gastrointestinal tissues were parallel to those of the pure pancreatic glucagon standard, and both antisera (30-K and K-44) measured the same concentrations. The highest concentration of gastrointestinal IRG was found in the fundus and corpus of the stomach. Presence of IRG in gastrointestinal tissues of depancreatized dogs indicates that gastrointestinal cells can not only secrete but also store large amounts of IRG. Extracts of mucosa of stomach fundus were further purified by gel filtration on Biogel P-30 columns. The immunoreactivity in the eluate was assayed by 30-K and a strongly crossreacting antibody, K-4023. One pooled fraction corresponding to marker pancreatic glucagon in its elution volume was found to contain the largest amount of IRG and the highest specific immunoreactivity (IRG/protein concentration). This fraction showed also the highest activity in a glucagon-receptor assay system. Disc gel electrophoresis in the presence of urea resolved this fraction into three immunoreactive components, one of which was identical to pancreatic glucagon in its electrophoretic mobility. It appears, therefore, that mucosa of the upper stomach in the dog contains a polypeptide similar to pancreatic glucagon. We conclude that (a) hyperglucagonemia in the dog can result from excessive secretion of IRG not only by the pancreatic alpha cells but also by cells of the gastrointestinal tract; (b) the highest IRG concentration was found in fundus and corpus of the stomach and lower concentrations throughout the gastrointestinal tract; (c) the IRG component in the stomach displayed immunologic and physical properties similar to pancreatic glucagon.", "contents": "Measurement and partial characterization of immunoreactive glucagon in gastrointestinal tissues of dogs. We have reported previously that increasing amounts of immunoreactive glucagon (IRG), measured by four specific antisera, appeared in plasma of depancreatized insulin-deficient dogs. It was therefore concluded that pancreatectomy was not accompanied by glucagon deficiency in the dog, but instead excessive amounts of extrapancreatic IRG could contribute to the diabetic syndrome. In order to locate the source of extrapancreatic glucagon, tissue extracts were assayed with anti-glucagon sera 30-K and K-44, which cross-react minimally with crude gut extracts. IRG was detected in all gastrointestinal tissues and in the salivary glands, but not in extracts of liver, kidney, brain, heart atrium, and adenohypophysis. Immunologic dilution curves of extracts from all gastrointestinal tissues were parallel to those of the pure pancreatic glucagon standard, and both antisera (30-K and K-44) measured the same concentrations. The highest concentration of gastrointestinal IRG was found in the fundus and corpus of the stomach. Presence of IRG in gastrointestinal tissues of depancreatized dogs indicates that gastrointestinal cells can not only secrete but also store large amounts of IRG. Extracts of mucosa of stomach fundus were further purified by gel filtration on Biogel P-30 columns. The immunoreactivity in the eluate was assayed by 30-K and a strongly crossreacting antibody, K-4023. One pooled fraction corresponding to marker pancreatic glucagon in its elution volume was found to contain the largest amount of IRG and the highest specific immunoreactivity (IRG/protein concentration). This fraction showed also the highest activity in a glucagon-receptor assay system. Disc gel electrophoresis in the presence of urea resolved this fraction into three immunoreactive components, one of which was identical to pancreatic glucagon in its electrophoretic mobility. It appears, therefore, that mucosa of the upper stomach in the dog contains a polypeptide similar to pancreatic glucagon. We conclude that (a) hyperglucagonemia in the dog can result from excessive secretion of IRG not only by the pancreatic alpha cells but also by cells of the gastrointestinal tract; (b) the highest IRG concentration was found in fundus and corpus of the stomach and lower concentrations throughout the gastrointestinal tract; (c) the IRG component in the stomach displayed immunologic and physical properties similar to pancreatic glucagon."}
{"id": "PMID:186346", "title": "Intracellular enzymes of collagen biosynthesis in rat kidney in streptozotocin diabetes.", "content": "The activities of the four enzymes catalyzing intracellular post-translational modifications of the collagen polypeptide chains were assayed in the kidneys of rats with streptozotocin diabetes. When the changes in the four enzyme activities were expressed per milligram of protein in the 15,000 X g supernatant of the kidney homogenates, there were no changes in any of the enzyme activities at four weeks and only slight increases in the prolyl and lysyl hydroxylase activities at 12 weeks after the induction of diabetes. When the changes were expressed as total enzyme activities per two kidneys, again no changes were found in any enzyme activity at four weeks, but at 12 weeks significant increases were found in all four enzyme activities, namely prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase, and collagen glucosyltransferase. The data would be consistent with an increased collagen synthesis in diabetic kidneys, but they do not support the hypothesis that there might be specific changes in some of these enzyme activities or in the level of certain posttranslational modifications of the collagen polypeptide chains in this disease.", "contents": "Intracellular enzymes of collagen biosynthesis in rat kidney in streptozotocin diabetes. The activities of the four enzymes catalyzing intracellular post-translational modifications of the collagen polypeptide chains were assayed in the kidneys of rats with streptozotocin diabetes. When the changes in the four enzyme activities were expressed per milligram of protein in the 15,000 X g supernatant of the kidney homogenates, there were no changes in any of the enzyme activities at four weeks and only slight increases in the prolyl and lysyl hydroxylase activities at 12 weeks after the induction of diabetes. When the changes were expressed as total enzyme activities per two kidneys, again no changes were found in any enzyme activity at four weeks, but at 12 weeks significant increases were found in all four enzyme activities, namely prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase, and collagen glucosyltransferase. The data would be consistent with an increased collagen synthesis in diabetic kidneys, but they do not support the hypothesis that there might be specific changes in some of these enzyme activities or in the level of certain posttranslational modifications of the collagen polypeptide chains in this disease."}
{"id": "PMID:186347", "title": "Infant human pancreas. A potential source of islet tissue for transplantation.", "content": "Twelve pancreases from human infants one year old or less were analyzed for tissue insulin and amylase content before and after dispersal of pancreatic fragments by mincing and collagenase digestion. Tissue insulin and amylase content provide an index of pancreatic islet mass and exocrine digestive enzyme content, respectively. The results were compared with similar anaylses performed on juvenile and adult human pancreases before and after islet isolation and on intact and dispersed neonatal rat and adult rat pancreas. Infant human pancreas has an average tissue insulin concentration of 1,128 mug./gm. of tissue and a total insulin content of 1,718 mug/pancreas, as against values of 140 mug./gm. of tissue and 7,209 mug./pancreas for adult human pancreas. Average tissue amylase concentration is 0.24 mg./gm. of tissue in infant human pancreas and 3.0 mg./gm. of tissue in adult human pancreas. The insulin/amylase ratio in infant pancreas is 4,800, as against 46 in the adult pancreas. Neonatal rat pancreas, which can be dissociated and transplanted without separation of islet and exocrine components, has a similarly high tissue insulin and low tissue amylase content when compared with adult rat pancreases. Infant human pancreas has a total islet mass 24 per cent that of an adult human pancreas, and neonatal rat pancreas has a total islet mass 11 per cent of that of an adult rat pancreas. One neonatal rat pancreas prepared by minimal collagenase digestion can cure diabetes when transplanted via the portal vein to a rat. Following dispersal of infant human pancreas by collagenase digestion, the islet content and the insulin/amylase ratio of the recovered tissue equals or exceeds that which usually can be isolated from adult cadaver pancreases. Infant human pancreas is a rich source of islet tissue that is relatively uncontaminated by exocrine digestive enzymes. After dispersal, infant human pancreas may be ideal for transplantation to selected diabetic patients.", "contents": "Infant human pancreas. A potential source of islet tissue for transplantation. Twelve pancreases from human infants one year old or less were analyzed for tissue insulin and amylase content before and after dispersal of pancreatic fragments by mincing and collagenase digestion. Tissue insulin and amylase content provide an index of pancreatic islet mass and exocrine digestive enzyme content, respectively. The results were compared with similar anaylses performed on juvenile and adult human pancreases before and after islet isolation and on intact and dispersed neonatal rat and adult rat pancreas. Infant human pancreas has an average tissue insulin concentration of 1,128 mug./gm. of tissue and a total insulin content of 1,718 mug/pancreas, as against values of 140 mug./gm. of tissue and 7,209 mug./pancreas for adult human pancreas. Average tissue amylase concentration is 0.24 mg./gm. of tissue in infant human pancreas and 3.0 mg./gm. of tissue in adult human pancreas. The insulin/amylase ratio in infant pancreas is 4,800, as against 46 in the adult pancreas. Neonatal rat pancreas, which can be dissociated and transplanted without separation of islet and exocrine components, has a similarly high tissue insulin and low tissue amylase content when compared with adult rat pancreases. Infant human pancreas has a total islet mass 24 per cent that of an adult human pancreas, and neonatal rat pancreas has a total islet mass 11 per cent of that of an adult rat pancreas. One neonatal rat pancreas prepared by minimal collagenase digestion can cure diabetes when transplanted via the portal vein to a rat. Following dispersal of infant human pancreas by collagenase digestion, the islet content and the insulin/amylase ratio of the recovered tissue equals or exceeds that which usually can be isolated from adult cadaver pancreases. Infant human pancreas is a rich source of islet tissue that is relatively uncontaminated by exocrine digestive enzymes. After dispersal, infant human pancreas may be ideal for transplantation to selected diabetic patients."}
{"id": "PMID:186349", "title": "Peritoneoscopy and guided biopsy in the diagnosis of intraabdominal disease.", "content": "In 145 cases of intraabdominal disease, a laparotomy was considered the next diagnostic step, but peritoneoscopy was performed instead. In 37 cases with a suspicion of metatastic carcinoma, peritoneoscopy with guided biopsy demonstrated carcinoma in 29. In 32 cases, with biopsy-proven cirrhosis of the liver with high suspicion of a hepatoma, peritonescopy demonstrated the presence of hepatoma in 12. In 28 cases, protracted unexplained jaundice was present; nonsurgical causes for jaundice were found in 15. In 48 cases an exudative (protein greater than 2.5 per 100 ml) ascites was present. In 19 cases, either tuberculosis or carcinomatous implants of the peritoneum were found, and ovarian carcinoma was found in 9. Peritoneoscopy with guided biopsy obviated the need for laparotomy in 90% of these cases.", "contents": "Peritoneoscopy and guided biopsy in the diagnosis of intraabdominal disease. In 145 cases of intraabdominal disease, a laparotomy was considered the next diagnostic step, but peritoneoscopy was performed instead. In 37 cases with a suspicion of metatastic carcinoma, peritoneoscopy with guided biopsy demonstrated carcinoma in 29. In 32 cases, with biopsy-proven cirrhosis of the liver with high suspicion of a hepatoma, peritonescopy demonstrated the presence of hepatoma in 12. In 28 cases, protracted unexplained jaundice was present; nonsurgical causes for jaundice were found in 15. In 48 cases an exudative (protein greater than 2.5 per 100 ml) ascites was present. In 19 cases, either tuberculosis or carcinomatous implants of the peritoneum were found, and ovarian carcinoma was found in 9. Peritoneoscopy with guided biopsy obviated the need for laparotomy in 90% of these cases."}
{"id": "PMID:186350", "title": "Interaction of peptides related to secretin with hormone receptors on pancreatic acinar cells.", "content": "Three analogues of the carboxyl-terminal tricosapeptide of secretin (S5-27), one with glutamine replacing glutamic acid in position 9 (9-Gln-S5-27), a second with asparagine substituted for aspartic acid in position 15 (15-Asn-S5-27), and a third with both replacements (9-Gln-15-Asn-S5-27) were tested for their ability to interact with hormone receptors on dispersed pancreatic acinar cells. Each of these analogues inhibited binding of 125I-labeled vasoactive intestinal peptide (VIP). None of the analogues increased cellular cyclic AMP but each inhibited the increase in cellular cyclic AMP produced by secretin or VIP. At the high affinity VIP receptor (the low affinity secretin receptor) each analogue had an apparent affinity which was greater than that for S5-27, whereas at he low affinity VIP receptor (the high affinity secretin receptor), each of the analogues had an apparent affinity which was the same as that for S5-27. Thus, in S5-27, substituting glutamine in position 9 or asparagine in position 15 makes the fragment more VIP-like but not less secretin-like. These results also provide additional evidence that the receptor having a low affinity for secretin and a high affinity for VIP is functionally distinct from the receptor having a high affinity for secretin and a low affinity for VIP.", "contents": "Interaction of peptides related to secretin with hormone receptors on pancreatic acinar cells. Three analogues of the carboxyl-terminal tricosapeptide of secretin (S5-27), one with glutamine replacing glutamic acid in position 9 (9-Gln-S5-27), a second with asparagine substituted for aspartic acid in position 15 (15-Asn-S5-27), and a third with both replacements (9-Gln-15-Asn-S5-27) were tested for their ability to interact with hormone receptors on dispersed pancreatic acinar cells. Each of these analogues inhibited binding of 125I-labeled vasoactive intestinal peptide (VIP). None of the analogues increased cellular cyclic AMP but each inhibited the increase in cellular cyclic AMP produced by secretin or VIP. At the high affinity VIP receptor (the low affinity secretin receptor) each analogue had an apparent affinity which was greater than that for S5-27, whereas at he low affinity VIP receptor (the high affinity secretin receptor), each of the analogues had an apparent affinity which was the same as that for S5-27. Thus, in S5-27, substituting glutamine in position 9 or asparagine in position 15 makes the fragment more VIP-like but not less secretin-like. These results also provide additional evidence that the receptor having a low affinity for secretin and a high affinity for VIP is functionally distinct from the receptor having a high affinity for secretin and a low affinity for VIP."}
{"id": "PMID:186351", "title": "Effect of propranolol on bile acid- and cholera enterotoxin-stimulated cAMP and secretion in rabbit intestine.", "content": "Stimulation of net secretion by deoxycholic acid (DCA) in the colon and by cholera enterotoxin (CE) in the jejunum is mediated by cAMP. Propranolol (Pr) inhibits adenylate cyclase (AC) activity and net secretion induced by bile acid in the colon. The aim of this study was to assess the organ specificity of DCA and CE as well as the selectivity of Pr inhibition. Three colonic and three jejunal loops were prepared in each of 8 rabbits treated intravenously with Pr, 4 mg per kg, 1/2 hr before loop construction and in each of 10 untreated control rabbits. One milliliter of DCA, 6 mM, CE, 10 mug per ml, or heat-inactivated CE or 0.9% NaCl, as basal controls were injected in random order into each of the loops. The volume of luminal fluid and mucosal AC were measured in each intestinal loop 5 hr later. DCA in the colon stimulated AC 2-fold (P less than 0.01) and luminal fluid 15-fold (P less than 0.01). CE in the jejunum stimulated AC 2.3-fold (P less than 0.01) and luminal fluid 9-fold (P less that 0.01). No significant effects on volume or AC occurred in response to CE in the colon or to DCA in the jejunum. Pr pretreatment completely prevented the stimulation of AC and luminal fluid by DCA in the colon but did not affect the action of CE in the jejunum of the same animals. Thus, DCA and CE are organ-specific stimulants of cAMP systems, and Pr is a selective inhibitor of certain inducers of cAMP and net secretion.", "contents": "Effect of propranolol on bile acid- and cholera enterotoxin-stimulated cAMP and secretion in rabbit intestine. Stimulation of net secretion by deoxycholic acid (DCA) in the colon and by cholera enterotoxin (CE) in the jejunum is mediated by cAMP. Propranolol (Pr) inhibits adenylate cyclase (AC) activity and net secretion induced by bile acid in the colon. The aim of this study was to assess the organ specificity of DCA and CE as well as the selectivity of Pr inhibition. Three colonic and three jejunal loops were prepared in each of 8 rabbits treated intravenously with Pr, 4 mg per kg, 1/2 hr before loop construction and in each of 10 untreated control rabbits. One milliliter of DCA, 6 mM, CE, 10 mug per ml, or heat-inactivated CE or 0.9% NaCl, as basal controls were injected in random order into each of the loops. The volume of luminal fluid and mucosal AC were measured in each intestinal loop 5 hr later. DCA in the colon stimulated AC 2-fold (P less than 0.01) and luminal fluid 15-fold (P less than 0.01). CE in the jejunum stimulated AC 2.3-fold (P less than 0.01) and luminal fluid 9-fold (P less that 0.01). No significant effects on volume or AC occurred in response to CE in the colon or to DCA in the jejunum. Pr pretreatment completely prevented the stimulation of AC and luminal fluid by DCA in the colon but did not affect the action of CE in the jejunum of the same animals. Thus, DCA and CE are organ-specific stimulants of cAMP systems, and Pr is a selective inhibitor of certain inducers of cAMP and net secretion."}
{"id": "PMID:186352", "title": "Effect of indomethacin on cholera-induced fluid movement, unidirectional sodium fluxes, and intestinal cAMP.", "content": "Cholera enterotoxin (CT) produces intestinal secretion associated with an elevation of intestinal cyclic AMP (cAMP). Indomethacin, a potent inhibitor of prostaglandin (PG) synthesis, decreases CT-induced secretion, although a role for PG in this process has not been demonstrated. The purpose of this study was to measure the effects of indomethacin on net fluid movement and unidirectional Na fluxes in rabbit jejunal loops exposed to CT and to correlate these findings with intestinal cAMP levels. In untreated animals (no indomethacin), CT loops secreted 0.37 ml per cm per 4 hr compared to absorption in control loops of 0.23 ml per cm per 4 hr (P less than 0.001). In indomethacin-treated animals, there was a striking reduction of secretion in CT loops (0.07 ml per cm per 4 hr, P less than 0.001). Absorption in control loops in indomethacin animals was greater than in untreated animals (0.42 ml per cm per 4 hr, P less than 0.02). Unidirectional Na fluxes were greatly depressed in indomethacin animals at 1 h in both CT and control loops. This effect disappeared by 4 hr. Intestinal cAMP levels in CT loops, although not elevated at 1 hr despite the onset of secretion, were significantly elevated at 4 hr. Indomethacin did not alter cAMP levels at 1 and 4 hr in either cholera or control loops. These studies support the view that PG synthesis is not involved in CT-induced elevation of intestinal cAMP. Indomethacin may depress intestinal secretion by inhibiting a PG-mediated step beyond the generation of cAMP or by acting on some other, as yet unidentified, biological mechanism involved in intestinal secretion.", "contents": "Effect of indomethacin on cholera-induced fluid movement, unidirectional sodium fluxes, and intestinal cAMP. Cholera enterotoxin (CT) produces intestinal secretion associated with an elevation of intestinal cyclic AMP (cAMP). Indomethacin, a potent inhibitor of prostaglandin (PG) synthesis, decreases CT-induced secretion, although a role for PG in this process has not been demonstrated. The purpose of this study was to measure the effects of indomethacin on net fluid movement and unidirectional Na fluxes in rabbit jejunal loops exposed to CT and to correlate these findings with intestinal cAMP levels. In untreated animals (no indomethacin), CT loops secreted 0.37 ml per cm per 4 hr compared to absorption in control loops of 0.23 ml per cm per 4 hr (P less than 0.001). In indomethacin-treated animals, there was a striking reduction of secretion in CT loops (0.07 ml per cm per 4 hr, P less than 0.001). Absorption in control loops in indomethacin animals was greater than in untreated animals (0.42 ml per cm per 4 hr, P less than 0.02). Unidirectional Na fluxes were greatly depressed in indomethacin animals at 1 h in both CT and control loops. This effect disappeared by 4 hr. Intestinal cAMP levels in CT loops, although not elevated at 1 hr despite the onset of secretion, were significantly elevated at 4 hr. Indomethacin did not alter cAMP levels at 1 and 4 hr in either cholera or control loops. These studies support the view that PG synthesis is not involved in CT-induced elevation of intestinal cAMP. Indomethacin may depress intestinal secretion by inhibiting a PG-mediated step beyond the generation of cAMP or by acting on some other, as yet unidentified, biological mechanism involved in intestinal secretion."}
{"id": "PMID:186348", "title": "[Attempted protection against experimental endotoxic shock].", "content": "Protection against endotoxin challenge. The AA. have summarized shortly some experimental data dealing with trials of protection against endotoxin challenge pointing out, mostly, the effects of phosphate-containing compounds, as well as dextrane, anticoagulants, platelets, polymyxin B, and serum antiendotoxin and Lipid A antiserum. They have reported some experiments carried out by means of Limulus amebocyte lysate.", "contents": "[Attempted protection against experimental endotoxic shock]. Protection against endotoxin challenge. The AA. have summarized shortly some experimental data dealing with trials of protection against endotoxin challenge pointing out, mostly, the effects of phosphate-containing compounds, as well as dextrane, anticoagulants, platelets, polymyxin B, and serum antiendotoxin and Lipid A antiserum. They have reported some experiments carried out by means of Limulus amebocyte lysate."}
{"id": "PMID:186353", "title": "Stimulation of colonic glycoprotein synthesis by dibutyryl cyclic AMP and theophylline.", "content": "The effects of dibutyryl cyclic AMP (B2cAMP) and theophylline on glyoprotein synthesis in rabbit colon were studied in mucosal organ cultures using [3H]glucosamine as a precursor. Addition of B2cAMP (1 mm) to culture medium caused a significant increase in glycoprotein synthesis after 12 and 24 hr compared with biopsies cultured in control medium. The increase in glycoprotein synthesis was observed only if the cyclic nucleotide was present continuously in the incubation medium for at least 12 hr. The stimulatory effect of B2cAMP on [3H]glucosamine incorporation was blocked by cycloheximide. B2cAMP also stimulated mucosal uptake of glucosamine into the intracellular pool and markedly enhanced specific activity of mucosa galactosyltransferase, an enzyme involved in glycoprotein synthesis. Addition of 5mM theophylline caused a greater than 2-fold increase in cAMP levels, which was also accompanied by an increase in glucosamine uptake and incorporation into mucosal glycoproteins. This study demonstrates that elevation of intracellular cAMP concentration in colon epithelium in vitro is associated with an increase in glycoprotein synthesis. These effects may be mediated in part by (1) increased uptake of glycoprotein precursors such as glucosamine, and (2) increased activity of glycoprotein synthetic enzymes.", "contents": "Stimulation of colonic glycoprotein synthesis by dibutyryl cyclic AMP and theophylline. The effects of dibutyryl cyclic AMP (B2cAMP) and theophylline on glyoprotein synthesis in rabbit colon were studied in mucosal organ cultures using [3H]glucosamine as a precursor. Addition of B2cAMP (1 mm) to culture medium caused a significant increase in glycoprotein synthesis after 12 and 24 hr compared with biopsies cultured in control medium. The increase in glycoprotein synthesis was observed only if the cyclic nucleotide was present continuously in the incubation medium for at least 12 hr. The stimulatory effect of B2cAMP on [3H]glucosamine incorporation was blocked by cycloheximide. B2cAMP also stimulated mucosal uptake of glucosamine into the intracellular pool and markedly enhanced specific activity of mucosa galactosyltransferase, an enzyme involved in glycoprotein synthesis. Addition of 5mM theophylline caused a greater than 2-fold increase in cAMP levels, which was also accompanied by an increase in glucosamine uptake and incorporation into mucosal glycoproteins. This study demonstrates that elevation of intracellular cAMP concentration in colon epithelium in vitro is associated with an increase in glycoprotein synthesis. These effects may be mediated in part by (1) increased uptake of glycoprotein precursors such as glucosamine, and (2) increased activity of glycoprotein synthetic enzymes."}
{"id": "PMID:186354", "title": "[Pathogenesis, morphology, prognosis, clinical course and therapy of cystosarcoma phyllodes mammae (author's transl)].", "content": "Our investigation of 20 cases of C. ph. of the breast in women aged between 12 and 70 years yielded the following results: 1. In all cases a fibroadenoma or remnants of such a tumor were seen alongside with C. ph. A C. ph. therefore always develops on the base of a benign fibroadenoma of the breast. 2. The mitotic proliferation of the epithelium induces a proliferation of the myoepithelial cells which form the stromal portion of the tumor and can differentiate in to fibroblasts, lipoblasts, smooth muscle cells, reticulum cells, cartilage cells, osteoid cells or bone cells. The C. ph. of the female breast should thus be seen as an adenomyothelioma. Malignant degeneration of stromal cells possibly with haematogenous metastasis is observed in some cases. Concurrent malignant change of the epithelium (carcinosarcoma) is extremely rare and leads to lymph node metastases. 3. At the time being, there is no standardized and/or schematic treatment available. The therapy should be performed according to the size and growth of the tumor into the surrounding tissue, from simple excision to mastectomy. Radiation therapy ist not effective.", "contents": "[Pathogenesis, morphology, prognosis, clinical course and therapy of cystosarcoma phyllodes mammae (author's transl)]. Our investigation of 20 cases of C. ph. of the breast in women aged between 12 and 70 years yielded the following results: 1. In all cases a fibroadenoma or remnants of such a tumor were seen alongside with C. ph. A C. ph. therefore always develops on the base of a benign fibroadenoma of the breast. 2. The mitotic proliferation of the epithelium induces a proliferation of the myoepithelial cells which form the stromal portion of the tumor and can differentiate in to fibroblasts, lipoblasts, smooth muscle cells, reticulum cells, cartilage cells, osteoid cells or bone cells. The C. ph. of the female breast should thus be seen as an adenomyothelioma. Malignant degeneration of stromal cells possibly with haematogenous metastasis is observed in some cases. Concurrent malignant change of the epithelium (carcinosarcoma) is extremely rare and leads to lymph node metastases. 3. At the time being, there is no standardized and/or schematic treatment available. The therapy should be performed according to the size and growth of the tumor into the surrounding tissue, from simple excision to mastectomy. Radiation therapy ist not effective."}
{"id": "PMID:186356", "title": "Serum immunoreactive corticotrophin and response to metyrapone in old age in man.", "content": "Attempts have been made to establish the level of immunoreactive corticotrophin (IR-ACTH) in serum in healthy subjects with partts were investigated and the clinical and biochemical condition s of selection specified. Serum IR-ACTH was determined by a radioimmunoassay procedure using an N-terminal antibody produced against the 1--24 sequence of the conrticotrophin molecule. The morning level of serum IR-ACTH was determined in 115 fasting healthy subjects, range less than 16--210 pg/ml, median 94 pg/ml (3rd International Standard preparation). The level was found to be unchanged within the age interval 20--94 years, irrespective of sex. Thy nycterohemeral variation of the IR-ACTH concentration in serum was studied in 11 sibjects. A rhythmic variation of the IR-ACTH level was not constantly found and age-related difference in the temporal pattern was not demonstrated. In 10 young and 10 elderly subjects a metyrapone test was carried out and the IR-ACTH response was determined. The rise in serum IR-ACTH concentration varied between 20 and 739 pg/ml. Any significant age-related difference in response was not found. The interpretation of the present results with respect to the decreased secretory activity of the glucocorticoid producing system in the aged is discussed. It was concluded that the findings in this study did not indicate a primary deficiency of the axis of the glucocorticoid producing system, neither at the pituitary level nor at the adrenocortical level, as a causal factor to the decreased glucocorticoid production in old age.", "contents": "Serum immunoreactive corticotrophin and response to metyrapone in old age in man. Attempts have been made to establish the level of immunoreactive corticotrophin (IR-ACTH) in serum in healthy subjects with partts were investigated and the clinical and biochemical condition s of selection specified. Serum IR-ACTH was determined by a radioimmunoassay procedure using an N-terminal antibody produced against the 1--24 sequence of the conrticotrophin molecule. The morning level of serum IR-ACTH was determined in 115 fasting healthy subjects, range less than 16--210 pg/ml, median 94 pg/ml (3rd International Standard preparation). The level was found to be unchanged within the age interval 20--94 years, irrespective of sex. Thy nycterohemeral variation of the IR-ACTH concentration in serum was studied in 11 sibjects. A rhythmic variation of the IR-ACTH level was not constantly found and age-related difference in the temporal pattern was not demonstrated. In 10 young and 10 elderly subjects a metyrapone test was carried out and the IR-ACTH response was determined. The rise in serum IR-ACTH concentration varied between 20 and 739 pg/ml. Any significant age-related difference in response was not found. The interpretation of the present results with respect to the decreased secretory activity of the glucocorticoid producing system in the aged is discussed. It was concluded that the findings in this study did not indicate a primary deficiency of the axis of the glucocorticoid producing system, neither at the pituitary level nor at the adrenocortical level, as a causal factor to the decreased glucocorticoid production in old age."}
{"id": "PMID:186363", "title": "[Ulnar nerve neuropathy in the elbow region: surgical findings and conclusions about the etiologic mechanism and indications for surgery].", "content": "The operative findings of 191 cases of so-called tardy ulnar neuritis are demonstrated. They may be divided into 2 groups, neuropathies associated with (67 cases) and without dislocation or subluxation of the nerve (124 cases). Cases of ulnar neuritis associated with dislocation of the nerve showing no other pathologic changes indicate that dislocation of the nerve alone may account for clinical signs. The next step is the formation of adhesions followed at a later date by formation of a pseudoneuroma. As this condition is mostly of congenital origin an additional factor is needed for including clinical manifestations such as direct or chronic professional trauma. Not enough importance has been attached to the strong triceps, with large muscle mass reaching far down to the olecranon, which might cause irritation of the nerve by pressing it against the wall of the sulcus or dislocating it over the epicondyle. In cases of neuropathy without dislocation/subluxation there is always a pathological finding even when there is no pseudoneuroma. The m. epitrochleoanconaeus is found in this category (14 cases, 11%). The cubital tunnel syndrom of OSBORNE in a very large sense (all possible causes of compression distal to the sulcus) has been found 28 times. Therapeutic measures aim at taking the nerve away from the causative irritation (anterior transposition) or at erradicating the cause (resection of the epicondyle, section of the arcus tendineus, excision of a tumor etc.). OSBORNE's operation has been performed only thrice. Subluxation or dislocation of the nerve may follow this procedure or the nerve is left more exposed to pressure than before. Deep submuscular transposition is preferred in patients less than 50 years old but other factors may determine the choice between deep and subcutaneous transposition such as the cause of the neuropathy, arthritis of the elbow joint, strength of the flexor muscle mass etc.", "contents": "[Ulnar nerve neuropathy in the elbow region: surgical findings and conclusions about the etiologic mechanism and indications for surgery]. The operative findings of 191 cases of so-called tardy ulnar neuritis are demonstrated. They may be divided into 2 groups, neuropathies associated with (67 cases) and without dislocation or subluxation of the nerve (124 cases). Cases of ulnar neuritis associated with dislocation of the nerve showing no other pathologic changes indicate that dislocation of the nerve alone may account for clinical signs. The next step is the formation of adhesions followed at a later date by formation of a pseudoneuroma. As this condition is mostly of congenital origin an additional factor is needed for including clinical manifestations such as direct or chronic professional trauma. Not enough importance has been attached to the strong triceps, with large muscle mass reaching far down to the olecranon, which might cause irritation of the nerve by pressing it against the wall of the sulcus or dislocating it over the epicondyle. In cases of neuropathy without dislocation/subluxation there is always a pathological finding even when there is no pseudoneuroma. The m. epitrochleoanconaeus is found in this category (14 cases, 11%). The cubital tunnel syndrom of OSBORNE in a very large sense (all possible causes of compression distal to the sulcus) has been found 28 times. Therapeutic measures aim at taking the nerve away from the causative irritation (anterior transposition) or at erradicating the cause (resection of the epicondyle, section of the arcus tendineus, excision of a tumor etc.). OSBORNE's operation has been performed only thrice. Subluxation or dislocation of the nerve may follow this procedure or the nerve is left more exposed to pressure than before. Deep submuscular transposition is preferred in patients less than 50 years old but other factors may determine the choice between deep and subcutaneous transposition such as the cause of the neuropathy, arthritis of the elbow joint, strength of the flexor muscle mass etc."}
{"id": "PMID:186364", "title": "[Ulnar nerve neuropathy in the wrist region: surgical findings].", "content": "The author describes the operative findings in 20 cases of compression of the ulnar nerve at the wrist. Adhesions with or without compression of the nerve, neuroma formation and compression by a ganglion are the most frequent findings. In some cases an enlarged artery is compressing the nerve. In one case a loose pisiform bone was causing the irritation. Despite clinical and electromyographical symptoms there was no pathological finding in 2 cases.", "contents": "[Ulnar nerve neuropathy in the wrist region: surgical findings]. The author describes the operative findings in 20 cases of compression of the ulnar nerve at the wrist. Adhesions with or without compression of the nerve, neuroma formation and compression by a ganglion are the most frequent findings. In some cases an enlarged artery is compressing the nerve. In one case a loose pisiform bone was causing the irritation. Despite clinical and electromyographical symptoms there was no pathological finding in 2 cases."}
{"id": "PMID:186365", "title": "[Decompression of individual nerves in anatomical strictures in polyneuropathies].", "content": "During clinical and electromyographical examination of one patient with diabetic and one with alcoholic polyneuropathy we found an especially severe lesion of the ulnar nerve at the elbow on one side. As the polyneuropathy generally affects the nerves symmetrically we presumed in addition some other most probably ulnar nerve compression syndrome at the elbow. Both patients were operated and the nerves were transposed (Prof. NIGST). The local finding during the operation, the improvement of the paresis of ulnar nerve and the worsening of the polyneuropathy--found simultaneously at control after 2 and 4 years--confirmed our supposition. Should in cases of polyneuropathy an especially severely damaged nerve be found, one ought to think of the possibility of an additional mechanical lesion and treat the patient accordingly.", "contents": "[Decompression of individual nerves in anatomical strictures in polyneuropathies]. During clinical and electromyographical examination of one patient with diabetic and one with alcoholic polyneuropathy we found an especially severe lesion of the ulnar nerve at the elbow on one side. As the polyneuropathy generally affects the nerves symmetrically we presumed in addition some other most probably ulnar nerve compression syndrome at the elbow. Both patients were operated and the nerves were transposed (Prof. NIGST). The local finding during the operation, the improvement of the paresis of ulnar nerve and the worsening of the polyneuropathy--found simultaneously at control after 2 and 4 years--confirmed our supposition. Should in cases of polyneuropathy an especially severely damaged nerve be found, one ought to think of the possibility of an additional mechanical lesion and treat the patient accordingly."}
{"id": "PMID:186366", "title": "[The fibrolipomatous hypertrophy of the main nerves of the upper extremity].", "content": "10 cases of lipofibromatous hypertrophy of the main nerves in the upper limb in 7 female and 3 male patients are described. In 1 case at the level of the middle third of the upper arm and in 6 cases at the level of the wrist and neighboring areas. In 2 patients these pathological changes were found in the ulnar nerve, in 1 case the hypertrophy was limited to the upper arm, in the other it extended all along the extremity from below the axilla to the wrist. Finally, in 1 case a 20 cm long hypertrophy was found at the level of the deep branch of the radial nerve (posterior interosseus nerve) in the lower arm below the elbow. The fibrous and lipomatous tissue snugly surrounds the fascicles and cannot be separated from them without damaging them, even if the finest microsurgical techniques are used. As the disease has been diagnosed in children as young as five years a congenital etiology has to be considered. The condition is distinct though from the disease of DEJERINE-SOTTAS or from that of von RECKLINGHAUSEN. The hypertrophic nerve is progressively submitted to a chronic compression in the naturally narrow passages (carpal tunnel, ulnar grove at the elbow, arcade of FROHSE) or it becomes painful and paretic after even minor trauma which leads probably to local oedema, intraneural bleeding and epineural compression. An external and internal decompression has to be carried out. Resection or defatting of the hypertrophic fascicles, however, should be avoided. In 2 of our cases the disease was anamnestically present for 45-50 years and clinically followed in another case for 18 years. The disease does not seem progressive. These cases show, that this disorder, which first appeared in the medical literature in 1964 and have been described by several authors in the median nerve, exists as well in the two other main nerves of the upper extremity.", "contents": "[The fibrolipomatous hypertrophy of the main nerves of the upper extremity]. 10 cases of lipofibromatous hypertrophy of the main nerves in the upper limb in 7 female and 3 male patients are described. In 1 case at the level of the middle third of the upper arm and in 6 cases at the level of the wrist and neighboring areas. In 2 patients these pathological changes were found in the ulnar nerve, in 1 case the hypertrophy was limited to the upper arm, in the other it extended all along the extremity from below the axilla to the wrist. Finally, in 1 case a 20 cm long hypertrophy was found at the level of the deep branch of the radial nerve (posterior interosseus nerve) in the lower arm below the elbow. The fibrous and lipomatous tissue snugly surrounds the fascicles and cannot be separated from them without damaging them, even if the finest microsurgical techniques are used. As the disease has been diagnosed in children as young as five years a congenital etiology has to be considered. The condition is distinct though from the disease of DEJERINE-SOTTAS or from that of von RECKLINGHAUSEN. The hypertrophic nerve is progressively submitted to a chronic compression in the naturally narrow passages (carpal tunnel, ulnar grove at the elbow, arcade of FROHSE) or it becomes painful and paretic after even minor trauma which leads probably to local oedema, intraneural bleeding and epineural compression. An external and internal decompression has to be carried out. Resection or defatting of the hypertrophic fascicles, however, should be avoided. In 2 of our cases the disease was anamnestically present for 45-50 years and clinically followed in another case for 18 years. The disease does not seem progressive. These cases show, that this disorder, which first appeared in the medical literature in 1964 and have been described by several authors in the median nerve, exists as well in the two other main nerves of the upper extremity."}
{"id": "PMID:186368", "title": "Comparison of protein components of the plasma membrane fraction from rat liver and Morris hepatomas 5123D and 7777.", "content": "Isolated plasma membrane fractions from rat liver and Morris hepatoma 5123D and 7777 were labelled with radioiodine 125I by a chemical or enzymatic procedure and then were solubilized in 2 per cent solution of sodium dodecyl sulphate containing 1 per cent 2-mercaptoethanol. Solubilized proteins were separated into 20--22 zones staining with Coomassie Brilliant Blue R-250 after disc gel electrophoresis (7.5 per cent polyacrylamide gel). The high similarity of electrophoretic patterns of polypeptide components of all three preparations of cellular membranes was found in distinction to apparent differnces in the amount and disposition of substances stained with Schiff's reagent. Some tentative conclusions were drawn on the disposition of proteins within membrane structure studied by the method of labelling by chemical and enzymatic procedures (distinguishing between extrinsic and integral proteins).", "contents": "Comparison of protein components of the plasma membrane fraction from rat liver and Morris hepatomas 5123D and 7777. Isolated plasma membrane fractions from rat liver and Morris hepatoma 5123D and 7777 were labelled with radioiodine 125I by a chemical or enzymatic procedure and then were solubilized in 2 per cent solution of sodium dodecyl sulphate containing 1 per cent 2-mercaptoethanol. Solubilized proteins were separated into 20--22 zones staining with Coomassie Brilliant Blue R-250 after disc gel electrophoresis (7.5 per cent polyacrylamide gel). The high similarity of electrophoretic patterns of polypeptide components of all three preparations of cellular membranes was found in distinction to apparent differnces in the amount and disposition of substances stained with Schiff's reagent. Some tentative conclusions were drawn on the disposition of proteins within membrane structure studied by the method of labelling by chemical and enzymatic procedures (distinguishing between extrinsic and integral proteins)."}
{"id": "PMID:186369", "title": "Histoenzymatic and ultrastructural changes in the hepatocytes of gamma-irradiated rabbits.", "content": "Ultrastructural changes and intracellular enzyme activities in the hepatocytes were studied in rabbits irradiated with 550 rads of gamma rays at 1,3,6,9,15 and 30 days after irradiation. Swelling and marked rarefaction of the mitochondrial matrix observed on the first day were followed by gradual condensation of the matrix between the 6th and 9th day. This state was accompanied by marked reduction in the succinate dehydrogenase activity, ehich gradually returned to the normal by the 30th day of observation. In the hyaloplasm, the most intense changes developed between the third and sixth day and were manifested by clearing of the cytoplasm and marked fragmentation of the endoplasmic membranes, with concurrent negligible decline of the lactate dehydrogenase activity and unchanged glucose-6-phosphatase activity. In the Golgi apparatus, vacuolization of the cytoplasm and fragmentation of smooth membranes were most pronounced on the 6th day and were correlated with a weakened and diffuse reaction for thiamine pyrophosphatase. The alkaline phosphatase activity was irregularly distributed in the lobule. The activities of lysosomal hydrolases, i.e. acid phosphatase, beta-glucuronidase and non-specific esterase, had various localizations within the lobules. The strongest deviations from the normal and of longest duration. (up to 9 days) were seen in the Browicz-Kupffer cells. Complex studies on the same material conducted concurrently with the use of different methods showed that radiation damages structure and function in unequal degrees. Moreover, within the same organ the cellular response to ionizing radiation varies according to the character, localization and functional state of the cells. Deviations from the normal state occur between the first and ninth days, most of the structural and functional elements showing sings of return to the normal about the 15th day after irradiation.", "contents": "Histoenzymatic and ultrastructural changes in the hepatocytes of gamma-irradiated rabbits. Ultrastructural changes and intracellular enzyme activities in the hepatocytes were studied in rabbits irradiated with 550 rads of gamma rays at 1,3,6,9,15 and 30 days after irradiation. Swelling and marked rarefaction of the mitochondrial matrix observed on the first day were followed by gradual condensation of the matrix between the 6th and 9th day. This state was accompanied by marked reduction in the succinate dehydrogenase activity, ehich gradually returned to the normal by the 30th day of observation. In the hyaloplasm, the most intense changes developed between the third and sixth day and were manifested by clearing of the cytoplasm and marked fragmentation of the endoplasmic membranes, with concurrent negligible decline of the lactate dehydrogenase activity and unchanged glucose-6-phosphatase activity. In the Golgi apparatus, vacuolization of the cytoplasm and fragmentation of smooth membranes were most pronounced on the 6th day and were correlated with a weakened and diffuse reaction for thiamine pyrophosphatase. The alkaline phosphatase activity was irregularly distributed in the lobule. The activities of lysosomal hydrolases, i.e. acid phosphatase, beta-glucuronidase and non-specific esterase, had various localizations within the lobules. The strongest deviations from the normal and of longest duration. (up to 9 days) were seen in the Browicz-Kupffer cells. Complex studies on the same material conducted concurrently with the use of different methods showed that radiation damages structure and function in unequal degrees. Moreover, within the same organ the cellular response to ionizing radiation varies according to the character, localization and functional state of the cells. Deviations from the normal state occur between the first and ninth days, most of the structural and functional elements showing sings of return to the normal about the 15th day after irradiation."}
{"id": "PMID:186370", "title": "Histochemistry of oxidative enzymes in experimental allergic encephalomyelitis.", "content": "The histoenzymic pattern of oxidative enzymes (G3PD, IDH, SD, G6PD,HBD, NADPH: dehydrogenase) was investigated in experimental allergic encephalomyelitis (EAE) produced in rats according to PATERSON [13]. The results obtained lead to following conclusions: (1) The neuroglia, including the white matter oligodendroglia of immunized rats, exhibits increased oxidoreductase activities; (2) The neuroallergic reaction induces some stimulation of the oxidoreductive metabolism of oligoden-droglia; (3) The enzymatic hyperactivity in EAE does not show any relation to the morphological signs of alterations of the myelin sheath.", "contents": "Histochemistry of oxidative enzymes in experimental allergic encephalomyelitis. The histoenzymic pattern of oxidative enzymes (G3PD, IDH, SD, G6PD,HBD, NADPH: dehydrogenase) was investigated in experimental allergic encephalomyelitis (EAE) produced in rats according to PATERSON [13]. The results obtained lead to following conclusions: (1) The neuroglia, including the white matter oligodendroglia of immunized rats, exhibits increased oxidoreductase activities; (2) The neuroallergic reaction induces some stimulation of the oxidoreductive metabolism of oligoden-droglia; (3) The enzymatic hyperactivity in EAE does not show any relation to the morphological signs of alterations of the myelin sheath."}
{"id": "PMID:186371", "title": "The long-term prognosis infantile spasms--the present condition of cases of infantile spasms followed in school age.", "content": "A follow-up study has been made of 25 cases with infantile spasms, all of whom were six years old or more at review. Only four (16%) out of 25 cases made a full recovery and attended normal school. Spasms ceased in 96% of all cases, but fits other than spasms (grand mal, tonic seizure, atonic seizure, myoclonic seizure, atypical absence and psychomotor seizure) occurred subsequently in 11 cases (44%). The EEG became normal in two cases (8%), but still showed modified hypsarhythmia in three cases (12%), \"epileptic non-hypsarhythmic\" discharges in 17 cases (68%) and non-specific abnormalities in three cases (12%). The important factors associated with good prognosis were normal development before the onset of spasms, late onset (seven months old or over) and short duration of spasms, the absence of other types of fit following spasms and lack of neurological abnormality. A bad prognosis was associated with abnormal development prior to the onset of spasms, early onset and long duration of spasms, the presence of other types of fit following spasms and evidence of any neyrological abnormality This follow-up may confirm that the therapy with ACTH-A has no significant effect on final mental state.", "contents": "The long-term prognosis infantile spasms--the present condition of cases of infantile spasms followed in school age. A follow-up study has been made of 25 cases with infantile spasms, all of whom were six years old or more at review. Only four (16%) out of 25 cases made a full recovery and attended normal school. Spasms ceased in 96% of all cases, but fits other than spasms (grand mal, tonic seizure, atonic seizure, myoclonic seizure, atypical absence and psychomotor seizure) occurred subsequently in 11 cases (44%). The EEG became normal in two cases (8%), but still showed modified hypsarhythmia in three cases (12%), \"epileptic non-hypsarhythmic\" discharges in 17 cases (68%) and non-specific abnormalities in three cases (12%). The important factors associated with good prognosis were normal development before the onset of spasms, late onset (seven months old or over) and short duration of spasms, the absence of other types of fit following spasms and lack of neurological abnormality. A bad prognosis was associated with abnormal development prior to the onset of spasms, early onset and long duration of spasms, the presence of other types of fit following spasms and evidence of any neyrological abnormality This follow-up may confirm that the therapy with ACTH-A has no significant effect on final mental state."}
{"id": "PMID:186372", "title": "[Improved demonstration of normal lymph nodes in lymphangiograms (author's transl)].", "content": "Lymphography with Lipiodol ultra fluid was carried out in eight domestic pigs. The purpose of the experiment was to obtain even distribution of the oil in normal lymph nodes in order to improve its diagnostic value. This was attempted by changes in pressure, temperature and by the addition of benzopyrone. By increasing injection pressure from 0.4 to 0.8 atmospheres, using a pump, it was possible to show more of the lymphatic tissue. Whether this would be possible in man is still not certain. The use of a benzopyrone preparation also improved contrast distribution in lymph nodes. Additional pelvic lymphatics were also seen. The improved distribution of oil is indicated by the altered pattern, strikingly even filling of the vacuoles and 10% incfreased filling rate.", "contents": "[Improved demonstration of normal lymph nodes in lymphangiograms (author's transl)]. Lymphography with Lipiodol ultra fluid was carried out in eight domestic pigs. The purpose of the experiment was to obtain even distribution of the oil in normal lymph nodes in order to improve its diagnostic value. This was attempted by changes in pressure, temperature and by the addition of benzopyrone. By increasing injection pressure from 0.4 to 0.8 atmospheres, using a pump, it was possible to show more of the lymphatic tissue. Whether this would be possible in man is still not certain. The use of a benzopyrone preparation also improved contrast distribution in lymph nodes. Additional pelvic lymphatics were also seen. The improved distribution of oil is indicated by the altered pattern, strikingly even filling of the vacuoles and 10% incfreased filling rate."}
{"id": "PMID:186373", "title": "[Cytomegalic virus infection in normal and disturbed immunity. Clinical and animal experiment studies].", "content": "Virological and serological studies of cytomegalovirus infections revealed following results: 1. The distribution of cytomegalovirus infections in the area of Munich can be compared with other European areas. 57% of adults have antibodies against the cytomegalovirus. 2. Cytomegalovirus is an important agent initiating infectious liver diseases in childhood. 3. The virus is also an important factor for severe cerebral retardation. 4. Studies in adult mice showed that a non-pathogenic strain of mouse cytomegalovirus can produce a fatal infection, when the immunological resistance was depressed by cytotoxic agents (i.e. cyclophosphamide, azathioprine, antilymphocyte serum). 5. Cytosine arabinoside inhibiting in vitro the replication of DNA viruses, increases in mice significantly the cytomegalovirus infection. Therefore cytosine arabinoside should be used very critically in the therapy of human cytomegalovirus infections.", "contents": "[Cytomegalic virus infection in normal and disturbed immunity. Clinical and animal experiment studies]. Virological and serological studies of cytomegalovirus infections revealed following results: 1. The distribution of cytomegalovirus infections in the area of Munich can be compared with other European areas. 57% of adults have antibodies against the cytomegalovirus. 2. Cytomegalovirus is an important agent initiating infectious liver diseases in childhood. 3. The virus is also an important factor for severe cerebral retardation. 4. Studies in adult mice showed that a non-pathogenic strain of mouse cytomegalovirus can produce a fatal infection, when the immunological resistance was depressed by cytotoxic agents (i.e. cyclophosphamide, azathioprine, antilymphocyte serum). 5. Cytosine arabinoside inhibiting in vitro the replication of DNA viruses, increases in mice significantly the cytomegalovirus infection. Therefore cytosine arabinoside should be used very critically in the therapy of human cytomegalovirus infections."}
{"id": "PMID:186374", "title": "[Pseudohypoparathyroidism. Disease of the second messenger].", "content": "Pseudo-hypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs and symptoms of hypoparathyroidism, which is resistant to parathyroid hormone (PTH). The knowledge of the role of cyclic adenosine monophosphate (cAMP) as a mediator of the action of PTH and the finding, that parathyroid extract in PHP could not stimulate the urinary excretion of cAMP, were necessary to explain the hitherto unknown pathogenesis of Pseudo-hypoparathyroidism. The PTH-sensitive adenylcyclase-system as second messenger is here unable to mediate the action of PTH on its target cells causing disturbances in calcium and phosphorus metabolism.", "contents": "[Pseudohypoparathyroidism. Disease of the second messenger]. Pseudo-hypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs and symptoms of hypoparathyroidism, which is resistant to parathyroid hormone (PTH). The knowledge of the role of cyclic adenosine monophosphate (cAMP) as a mediator of the action of PTH and the finding, that parathyroid extract in PHP could not stimulate the urinary excretion of cAMP, were necessary to explain the hitherto unknown pathogenesis of Pseudo-hypoparathyroidism. The PTH-sensitive adenylcyclase-system as second messenger is here unable to mediate the action of PTH on its target cells causing disturbances in calcium and phosphorus metabolism."}
{"id": "PMID:186375", "title": "[Changes of the renin-angiotensin-aldosterone system under contraceptive steroids. Contribution to the etiology of hypertension under hormonal contraceptives].", "content": "Treatment with hormonal contraceptives leads to a considerable stimulation of the renin-angiotensin-aldosterone-system. First of all, there is a 2,5- to 4fold increase of renin substrate synthesis in the liver. As a consequence, more angiotensin I and angiotensin II are released. Angiotensin II stimulates the secretion of aldosterone in the adrenals, thus producing a higher aldosterone concentration in plasma. The urinary excretion of aldosterone is elevated to a lesser degree, probably because of the simultaneously increased binding of aldosterone to plasma proteins. The release of renin is suppressed to 50% by negative feedback mechanisms. Some possible factors in the etiology of hypertension induced by oral contraceptives are discussed.", "contents": "[Changes of the renin-angiotensin-aldosterone system under contraceptive steroids. Contribution to the etiology of hypertension under hormonal contraceptives]. Treatment with hormonal contraceptives leads to a considerable stimulation of the renin-angiotensin-aldosterone-system. First of all, there is a 2,5- to 4fold increase of renin substrate synthesis in the liver. As a consequence, more angiotensin I and angiotensin II are released. Angiotensin II stimulates the secretion of aldosterone in the adrenals, thus producing a higher aldosterone concentration in plasma. The urinary excretion of aldosterone is elevated to a lesser degree, probably because of the simultaneously increased binding of aldosterone to plasma proteins. The release of renin is suppressed to 50% by negative feedback mechanisms. Some possible factors in the etiology of hypertension induced by oral contraceptives are discussed."}
{"id": "PMID:186376", "title": "13C-NMR studies of the membrane structure of enveloped virions (vesicular stomatitis virus).", "content": "The mobility of the lipids in the bilayer of the envelope of vesicular stomatitis virus has been probed over its complete space by the biosynthetic incorporation of [N-13CH3]- choline as a probe for the polar head groups and [3-13C]- and [11-13C] oleic acid and [16-13C]- palmitic acid for the hydrophobic region of the bilayer. These precursors were effectively incorporated as established by the concomitant administration of the same precursors in radioactive form. Spin lattice relaxation time measurements (T1) of the 13C enriched segments in complete virus envelope allowed estimation of their mobility. The mobility of the polar head groups is restricted, probably due to ionic interactions with neighbouring acidic phospholipids (phosphatidylserine) and/or acidic side chains of the glycoprotein (G-protein). The rigidity of the hydrophobic part of the bilayer is due to the high cholesterol content and interaction with the immersing polypeptide chains of the G- and possibly M-protein. The rigidity is limited to a depth of about 15 A ranging from the inner and outer surface, whereas the inner core of the bilayer is fluid. Tryptic cleavage of the hydrophilic part of the G-protein allows the lipophilic immersing polypeptide fragment to enter further the bilayer which then reduces the fluidity of the hydrocarbon chains in the core region by lipid-protein interactions.", "contents": "13C-NMR studies of the membrane structure of enveloped virions (vesicular stomatitis virus). The mobility of the lipids in the bilayer of the envelope of vesicular stomatitis virus has been probed over its complete space by the biosynthetic incorporation of [N-13CH3]- choline as a probe for the polar head groups and [3-13C]- and [11-13C] oleic acid and [16-13C]- palmitic acid for the hydrophobic region of the bilayer. These precursors were effectively incorporated as established by the concomitant administration of the same precursors in radioactive form. Spin lattice relaxation time measurements (T1) of the 13C enriched segments in complete virus envelope allowed estimation of their mobility. The mobility of the polar head groups is restricted, probably due to ionic interactions with neighbouring acidic phospholipids (phosphatidylserine) and/or acidic side chains of the glycoprotein (G-protein). The rigidity of the hydrophobic part of the bilayer is due to the high cholesterol content and interaction with the immersing polypeptide chains of the G- and possibly M-protein. The rigidity is limited to a depth of about 15 A ranging from the inner and outer surface, whereas the inner core of the bilayer is fluid. Tryptic cleavage of the hydrophilic part of the G-protein allows the lipophilic immersing polypeptide fragment to enter further the bilayer which then reduces the fluidity of the hydrocarbon chains in the core region by lipid-protein interactions."}
{"id": "PMID:186377", "title": "In vitro activation of a soluble cholesterol esterase from bovine adrenals by a cAMP-dependent protein kinase.", "content": "Properties and partial purification of the bovine adrenal cholesterol esterase from the 100000 X g supernatant fraction were investigated. Variations of the enzyme activity with time-dependent (enzymatic) and time-dependent (non enzymatic) effects have been demonstrated. Mg2 has been proved to inhibit the enzyme activity by a non-enzymatic effect in 50mM Tris/HCl buffer, pH 7.4. A time-dependent inactivation of the cholesterol esterase has been observed in the same buffer. The enzyme could be protected from this enzymatic inactivation by its substrate, cholesterol oleate. cAMP, ATP and Mg2 cuase a time-dependent stimulation of the enzyme in 50mM Tris/HCl buffer, pH 7.4. This result suggests that corticotropin activates the soluble cholesterol esterase from bovine adrenals via cAMP-dependent protein kinase. This view is strengthened by the incorporation of 32P radioactivity from [gamma-32P] ATP into the protein fraction of the 100,000 X g supernatant. The protein-bound 32P radioactivity could be co-purified with the enzyme activity during the partial purification of the soluble cholesterol esterase.", "contents": "In vitro activation of a soluble cholesterol esterase from bovine adrenals by a cAMP-dependent protein kinase. Properties and partial purification of the bovine adrenal cholesterol esterase from the 100000 X g supernatant fraction were investigated. Variations of the enzyme activity with time-dependent (enzymatic) and time-dependent (non enzymatic) effects have been demonstrated. Mg2 has been proved to inhibit the enzyme activity by a non-enzymatic effect in 50mM Tris/HCl buffer, pH 7.4. A time-dependent inactivation of the cholesterol esterase has been observed in the same buffer. The enzyme could be protected from this enzymatic inactivation by its substrate, cholesterol oleate. cAMP, ATP and Mg2 cuase a time-dependent stimulation of the enzyme in 50mM Tris/HCl buffer, pH 7.4. This result suggests that corticotropin activates the soluble cholesterol esterase from bovine adrenals via cAMP-dependent protein kinase. This view is strengthened by the incorporation of 32P radioactivity from [gamma-32P] ATP into the protein fraction of the 100,000 X g supernatant. The protein-bound 32P radioactivity could be co-purified with the enzyme activity during the partial purification of the soluble cholesterol esterase."}
{"id": "PMID:186378", "title": "3': 5'-Nucleotide phosphodiesterase in the superior cervical ganglion of the rat. Evidence for multiple forms and influence of the beta-adrenergic receptor system in the electrophoretic pattern of the enzyme.", "content": "Two forms of a cAMP phosphodiesterase were found in the superior cervical ganglia of the rat. The influence of various detergents on solubility and activity of the enzyme was studied. Two Km values were determined, one of 0.9mum and the other 270mum cAMP. Separation by polyacrylamide disc electrophoresis revealed four distinct peaks of enzyme activity. One of these activities was increased when ganglia were incubated with adrenaline for at least 4 h. The increase caused by adrenaline was unaffected when ganglia were pre-incubated with cycloheximide, but was blocked in the presence of propranolol, a beta-adrenergic antagonist. Incubation with dibutyryl cAMP for 4 h mimicked the effect of adrenaline. Brief incubation with adrenaline was without effect. Electrophoresis in the presence of 0.1% Lubrol W, a non-ionic detergent, showed that one band of activity disappeared, while the main peak of enzyme activity increased in size. Two-dimensional starch gel electrophoresis confirmed the results of the disc electrophoresis.", "contents": "3': 5'-Nucleotide phosphodiesterase in the superior cervical ganglion of the rat. Evidence for multiple forms and influence of the beta-adrenergic receptor system in the electrophoretic pattern of the enzyme. Two forms of a cAMP phosphodiesterase were found in the superior cervical ganglia of the rat. The influence of various detergents on solubility and activity of the enzyme was studied. Two Km values were determined, one of 0.9mum and the other 270mum cAMP. Separation by polyacrylamide disc electrophoresis revealed four distinct peaks of enzyme activity. One of these activities was increased when ganglia were incubated with adrenaline for at least 4 h. The increase caused by adrenaline was unaffected when ganglia were pre-incubated with cycloheximide, but was blocked in the presence of propranolol, a beta-adrenergic antagonist. Incubation with dibutyryl cAMP for 4 h mimicked the effect of adrenaline. Brief incubation with adrenaline was without effect. Electrophoresis in the presence of 0.1% Lubrol W, a non-ionic detergent, showed that one band of activity disappeared, while the main peak of enzyme activity increased in size. Two-dimensional starch gel electrophoresis confirmed the results of the disc electrophoresis."}
{"id": "PMID:186379", "title": "The role of the certified social worker in England's social services.", "content": "With the reorganization of England's social services into a single unified system, the professional called the certified qualified social worker is playing a key role in the administration and delivery of community services. The author describes some of the worker's activities and also presents an overview of hospital, day treatment, and outpatient services for adult psychiatric patients in the county of Warwickshire. One of the most effective programs is a system of voluntary group homes, operated by an area council of churches, for former psychiatric inpatients.", "contents": "The role of the certified social worker in England's social services. With the reorganization of England's social services into a single unified system, the professional called the certified qualified social worker is playing a key role in the administration and delivery of community services. The author describes some of the worker's activities and also presents an overview of hospital, day treatment, and outpatient services for adult psychiatric patients in the county of Warwickshire. One of the most effective programs is a system of voluntary group homes, operated by an area council of churches, for former psychiatric inpatients."}
{"id": "PMID:186380", "title": "An educational model for teaching living skills to long-term patients.", "content": "Establishing rehabilitation programs for long-term mental patients outside mental health settings can save mental health funds and further the patients' integration into the community, the author declares. He describes an approach that uses an educational model to teach patients the basic skills of everyday living. As \"students,\" they enroll in a course taught by a credentialed teacher and sponsored by the adult education department of the local high school. Mental health professionals are used only for consultation, and the cost to the local mental health program is minimal. A key element in the course is having the students participate in planning the curriculum.", "contents": "An educational model for teaching living skills to long-term patients. Establishing rehabilitation programs for long-term mental patients outside mental health settings can save mental health funds and further the patients' integration into the community, the author declares. He describes an approach that uses an educational model to teach patients the basic skills of everyday living. As \"students,\" they enroll in a course taught by a credentialed teacher and sponsored by the adult education department of the local high school. Mental health professionals are used only for consultation, and the cost to the local mental health program is minimal. A key element in the course is having the students participate in planning the curriculum."}
{"id": "PMID:186382", "title": "Fetal rhabdomyomatous nephroblastoma-a variant of Wilms' tumor.", "content": "The fetal rhabdomyomatous nephroblastoma is considered to be a predominantly monophasic mesenchymal variant of Wilms' tumor, which has not been seen in patients older than four years. It acts less aggressively than a Wilms tumor despite its much larger size. Its better prognosis appears to be related to either the absence of or the insignificant amounts of neoplastic epithelium. The bilaterality of this tumor in one-third of the cases, however, may negatively affect the overall prognosis, because complete resection may be impossible or because renal failure ensues.", "contents": "Fetal rhabdomyomatous nephroblastoma-a variant of Wilms' tumor. The fetal rhabdomyomatous nephroblastoma is considered to be a predominantly monophasic mesenchymal variant of Wilms' tumor, which has not been seen in patients older than four years. It acts less aggressively than a Wilms tumor despite its much larger size. Its better prognosis appears to be related to either the absence of or the insignificant amounts of neoplastic epithelium. The bilaterality of this tumor in one-third of the cases, however, may negatively affect the overall prognosis, because complete resection may be impossible or because renal failure ensues."}
{"id": "PMID:186383", "title": "Intracytoplasmic inclusion bodies in the chondrocytes of type I lethal achondrogenesis.", "content": "Lethal achondrogenesis in the past has been frequently confused with achondroplasia. Clinical and radiologic advances in the last decade have led to clear differentiation of this condition from other types of bone dysplasia. It is further separated into two types on the basis of radiographic and pathologic findings. Re-evaluation of the histologic features has led to the recognition of heretofore unrecognized intracytoplasmic inclusion bodies in the chondrocytes of type 1 achondrogenesis. The finding of inclusions strengthens the differentiation of the two types and may have implications for the pathogenesis of the form of chondrodystrophy.", "contents": "Intracytoplasmic inclusion bodies in the chondrocytes of type I lethal achondrogenesis. Lethal achondrogenesis in the past has been frequently confused with achondroplasia. Clinical and radiologic advances in the last decade have led to clear differentiation of this condition from other types of bone dysplasia. It is further separated into two types on the basis of radiographic and pathologic findings. Re-evaluation of the histologic features has led to the recognition of heretofore unrecognized intracytoplasmic inclusion bodies in the chondrocytes of type 1 achondrogenesis. The finding of inclusions strengthens the differentiation of the two types and may have implications for the pathogenesis of the form of chondrodystrophy."}
{"id": "PMID:186396", "title": "Propagation of mouse mammary tumor cell lines and production of mouse mammary tumor virus in a serum-free medium.", "content": "Five different mouse mammary tumor cell lines were propagated in a serum free medium. Evaluation of growth characteristics, including logarithmic growth, cell population increase, protein production and days to confluency, showed serum-free medium comparable to serum-containing medium. Mouse mammary tumor virus expression and production, in C3H and GR tumor cell lines, as determined by virus particle counting and RNA dependent DNA polymerase assays, subsequent to dexamethasone stimulation revealed equivalent to higher levels of virus in serum-free medium as compared to serum-containing medium.", "contents": "Propagation of mouse mammary tumor cell lines and production of mouse mammary tumor virus in a serum-free medium. Five different mouse mammary tumor cell lines were propagated in a serum free medium. Evaluation of growth characteristics, including logarithmic growth, cell population increase, protein production and days to confluency, showed serum-free medium comparable to serum-containing medium. Mouse mammary tumor virus expression and production, in C3H and GR tumor cell lines, as determined by virus particle counting and RNA dependent DNA polymerase assays, subsequent to dexamethasone stimulation revealed equivalent to higher levels of virus in serum-free medium as compared to serum-containing medium."}
{"id": "PMID:186397", "title": "The co-carcinogenic activity of 4-nitropyridine-1-oxide (4-NPO) and prevention of transformation by type-specific anti-viral antibodies.", "content": "Fischer rat embryo cells chronically infected with Rauscher murine leukemia virus, and known to be sensitive to transformation by potent chemical carcinogens, were transformed by the weak carcinogen 4-nitropyridine-1-oxide. Transformed cells grew in semi-solid agar and produced tumors in newborn Fischer rats. Transformation was inhibited by antisera specific for the ecotropic Rauscher murine leukemia virus, but not by antisera of equal toxicity specific for xenotropic Swiss mouse AT-124 virus.", "contents": "The co-carcinogenic activity of 4-nitropyridine-1-oxide (4-NPO) and prevention of transformation by type-specific anti-viral antibodies. Fischer rat embryo cells chronically infected with Rauscher murine leukemia virus, and known to be sensitive to transformation by potent chemical carcinogens, were transformed by the weak carcinogen 4-nitropyridine-1-oxide. Transformed cells grew in semi-solid agar and produced tumors in newborn Fischer rats. Transformation was inhibited by antisera specific for the ecotropic Rauscher murine leukemia virus, but not by antisera of equal toxicity specific for xenotropic Swiss mouse AT-124 virus."}
{"id": "PMID:186398", "title": "[Atypical pneumonia, etiology and possibilities for the diagnosis (author's transl)].", "content": "Beginning with the antimicrobial chemotherapy a decrease in the incidence of bacterial pneumonias is accompanied by a relative increase in the incidence of the so-called atypical pneumonia. This disease syndrome is predominantly caused by Mycoplasma pneumoniae, Chlamydia psittaci, Coxiella burneti and various viruses. In addition, bacteria which are usually involved in lobar pneumonia may occasionally cause atypical pneumonias. The present publication is concerned with the most frequently occurring causative agents of atypical pneumonia, the epidemiology of the disease and the possibilities for the diagnosis.", "contents": "[Atypical pneumonia, etiology and possibilities for the diagnosis (author's transl)]. Beginning with the antimicrobial chemotherapy a decrease in the incidence of bacterial pneumonias is accompanied by a relative increase in the incidence of the so-called atypical pneumonia. This disease syndrome is predominantly caused by Mycoplasma pneumoniae, Chlamydia psittaci, Coxiella burneti and various viruses. In addition, bacteria which are usually involved in lobar pneumonia may occasionally cause atypical pneumonias. The present publication is concerned with the most frequently occurring causative agents of atypical pneumonia, the epidemiology of the disease and the possibilities for the diagnosis."}
{"id": "PMID:186399", "title": "Immunoglobulin content and antibody activity in an artificial body cavity.", "content": "Artificial body cavities (ABC) were created by the insertion of hollow polyethylene balls in the subcutaneous tissue of rabbits. After two months no inflammatory reaction could be detected, the ABC was enveloped by a membranous structure, and the cavity contained about 20 ml of fluid. The protein concentration was about 3 times, and the IgG about 8 times, lower in the ABC fluids than in the corresponding serum. At the same time the antibody titers against sheep red blood cells (SRBC), human IgG and herpes simplex virus type 1 (HSV) were about 20 200 times lower than in the corresponding serum samples. The IgG molecules appeared to be undamaged as shown by the presence of various allotypes and by the elution pattern from G-200 column. Testing the protective activity of ABC fluids and of serum against HSV infection showed that ABC fluids had no protective activity. The experiments suggest that the membranous structure selected among classes of Ig and probably among other serum proteins. In addition, the IgG molecules with antibody activity against various inoculated antigens were selectively excluded to penetrate in the ABC. The ABC might be considered analogous to virtual cavities of the body surrounded by membranes and possibly to the extravascular compartment.", "contents": "Immunoglobulin content and antibody activity in an artificial body cavity. Artificial body cavities (ABC) were created by the insertion of hollow polyethylene balls in the subcutaneous tissue of rabbits. After two months no inflammatory reaction could be detected, the ABC was enveloped by a membranous structure, and the cavity contained about 20 ml of fluid. The protein concentration was about 3 times, and the IgG about 8 times, lower in the ABC fluids than in the corresponding serum. At the same time the antibody titers against sheep red blood cells (SRBC), human IgG and herpes simplex virus type 1 (HSV) were about 20 200 times lower than in the corresponding serum samples. The IgG molecules appeared to be undamaged as shown by the presence of various allotypes and by the elution pattern from G-200 column. Testing the protective activity of ABC fluids and of serum against HSV infection showed that ABC fluids had no protective activity. The experiments suggest that the membranous structure selected among classes of Ig and probably among other serum proteins. In addition, the IgG molecules with antibody activity against various inoculated antigens were selectively excluded to penetrate in the ABC. The ABC might be considered analogous to virtual cavities of the body surrounded by membranes and possibly to the extravascular compartment."}
{"id": "PMID:186400", "title": "Lymphocyte activation by cell separation procedures.", "content": "Cell separation techniques normally used to obtain subpopulations of lymphocytes were shown, under certain conditions, to render the cells cytotoxic towards a number of target-cells including autologous lymphocytes. To cause cytotoxicity, it was necessary to pass cells through glass wool and/or nylon wool columns equilibrated with media containing fresh plasma or serum. Cells lost activation upon overnight in vitro culture or treatment with trypsin. In addition to direct cell cytotoxicity, cells released heat labile cytotoxic factors and antibody during the separation procedures. The implications of the results for the interpretation of cell separation studies designed to attribute immunological effects to one or another cell type were discussed.", "contents": "Lymphocyte activation by cell separation procedures. Cell separation techniques normally used to obtain subpopulations of lymphocytes were shown, under certain conditions, to render the cells cytotoxic towards a number of target-cells including autologous lymphocytes. To cause cytotoxicity, it was necessary to pass cells through glass wool and/or nylon wool columns equilibrated with media containing fresh plasma or serum. Cells lost activation upon overnight in vitro culture or treatment with trypsin. In addition to direct cell cytotoxicity, cells released heat labile cytotoxic factors and antibody during the separation procedures. The implications of the results for the interpretation of cell separation studies designed to attribute immunological effects to one or another cell type were discussed."}
{"id": "PMID:186401", "title": "Mode of interaction of different polyanions with the first (C1,C1) the second (C2) and the fourth (C4) component of complement. IV. Activation of C1 in serum by polyanions.", "content": "Treatment of serum with dextransulphate polyvinylsulphate or polyanetholsulphonate resulted in a dose-dependent activation of C1 and C3; this was found for normal serum as well as for C4-deficient guinea-pig serum. Activation of C1 and C3 occurred at the same concentration of polyanions. The consumption of C3 in C4 deficient serum and the requirement of factor D of the alternative pathway indicate that C3 is activated via the alternative pathway.", "contents": "Mode of interaction of different polyanions with the first (C1,C1) the second (C2) and the fourth (C4) component of complement. IV. Activation of C1 in serum by polyanions. Treatment of serum with dextransulphate polyvinylsulphate or polyanetholsulphonate resulted in a dose-dependent activation of C1 and C3; this was found for normal serum as well as for C4-deficient guinea-pig serum. Activation of C1 and C3 occurred at the same concentration of polyanions. The consumption of C3 in C4 deficient serum and the requirement of factor D of the alternative pathway indicate that C3 is activated via the alternative pathway."}
{"id": "PMID:186409", "title": "Comparison of serological tests for antibody to hepatitis A antigen, using coded specimens from individuals infected with the MS-1 strain of hepatitis A virus.", "content": "To compare serological tests for antibody to hepatitis A antigen (anti-HA), we tested 15 paired serum specimens, submitted under code, from individuals infected with the MS-1 strain of hepatitis A virus. Immune electron microscopy (IEM), immune adherence hemagglutination (IAHA), and solid-phase radioimmunoassay (RIA) tests for anti-HA were performed with hepatitis A antigen (HA Ag) derived from human stool; results were also compared with previously reported titers determined by IAHA with HA Ag derived from marmoset liver. Antibody titers (IAHA and RIA) and ratings (IEM) determined with stool-derived HA Ag compared favorably, and a seroresponse to HA Ag was detected by all three methods for every serum pair tested. Differences in titers were noted between IAHA tests with liver-derived and with stool-derived HA Ag, but the discrepancies could be accounted for by differences in test technique. The agreement found in this study among the three techniques was quite good and confirms the specificity and sensitivity of tests for anti-HA that are done with stool-derived HA-Ag.", "contents": "Comparison of serological tests for antibody to hepatitis A antigen, using coded specimens from individuals infected with the MS-1 strain of hepatitis A virus. To compare serological tests for antibody to hepatitis A antigen (anti-HA), we tested 15 paired serum specimens, submitted under code, from individuals infected with the MS-1 strain of hepatitis A virus. Immune electron microscopy (IEM), immune adherence hemagglutination (IAHA), and solid-phase radioimmunoassay (RIA) tests for anti-HA were performed with hepatitis A antigen (HA Ag) derived from human stool; results were also compared with previously reported titers determined by IAHA with HA Ag derived from marmoset liver. Antibody titers (IAHA and RIA) and ratings (IEM) determined with stool-derived HA Ag compared favorably, and a seroresponse to HA Ag was detected by all three methods for every serum pair tested. Differences in titers were noted between IAHA tests with liver-derived and with stool-derived HA Ag, but the discrepancies could be accounted for by differences in test technique. The agreement found in this study among the three techniques was quite good and confirms the specificity and sensitivity of tests for anti-HA that are done with stool-derived HA-Ag."}
{"id": "PMID:186410", "title": "Viral infections in renal transplant recipients.", "content": "Cytomegalovirus (CMV) infections are common in renal transplant recipients. We studied 23 recipients prospectively to determine whether infections by other herpes-group and non-herpes-group viruses were also present. Sera, obtained at the time of surgery and periodically thereafter, were tested for antibody to CMV, herpes simplex virus (HSV), Epstein-Barr virus (EBV), parainfluenza viruses types 1, 2, and 3, and the viruses of measles and rubella. We found no evidence of an unusual incidence of primary or secondary infection by the non-herpesviruses tested. Rises to CMV, HSV, and EBV antibody titers occurred in 43, 38, and 32% of patients, respectively. All  serological rises to herpes-group viruses occurred in patients seropositive at the time of transplantation, with the exception of three patients who experienced primary CMV infections. We conclude that reactivation of all herpes-group viruses tested may occur in transplant recipients. Morbidity was associated only with primarly CMV infection.", "contents": "Viral infections in renal transplant recipients. Cytomegalovirus (CMV) infections are common in renal transplant recipients. We studied 23 recipients prospectively to determine whether infections by other herpes-group and non-herpes-group viruses were also present. Sera, obtained at the time of surgery and periodically thereafter, were tested for antibody to CMV, herpes simplex virus (HSV), Epstein-Barr virus (EBV), parainfluenza viruses types 1, 2, and 3, and the viruses of measles and rubella. We found no evidence of an unusual incidence of primary or secondary infection by the non-herpesviruses tested. Rises to CMV, HSV, and EBV antibody titers occurred in 43, 38, and 32% of patients, respectively. All  serological rises to herpes-group viruses occurred in patients seropositive at the time of transplantation, with the exception of three patients who experienced primary CMV infections. We conclude that reactivation of all herpes-group viruses tested may occur in transplant recipients. Morbidity was associated only with primarly CMV infection."}
{"id": "PMID:186411", "title": "Synergistic effect on mortality in mice with murine cytomegalovirus and Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections.", "content": "A synergistic effect on mortality was demonstrated in a combined infection of mice with murine cytomegalovirus (MCMV) and Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans. Mice infected intraperitoneally with a 0 to 20% lethal dose inoculum of MCMV 3 days prior to the intravenous injection of a 0 to 20% lethal dose inoculum of either the bacteria or fungus demonstrated a striking enhancement of mortality. MCMV-infected mice given Pseudomonas or Staphylococcus exhibited a 90 to 100% mortality within 24 to 48 h, whereas 80% of viral-infected animals injected with Candida died in 5 days. Injection of the bacteria or fungus at various times during the MCMV infection resulted in enhanced mortality on days 0,1,2, and 3 of the viral infection. Greatest synergism was observed on day 3, with a progressive decline in death rates thereafter. Immunization with MCMV abrogated the synergistic effect on mortality in all three combined infections. Immunization with Pseudomonas reduced mortality in the combined MCMV-Pseudomonas infection. These results indicate that mice exhibit a markedly enhanced susceptibility to bacterial and fungal infections during the course of the MCMV infection and suggest that the enhancement may be related to viral-induced alterations in host resistance.", "contents": "Synergistic effect on mortality in mice with murine cytomegalovirus and Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans infections. A synergistic effect on mortality was demonstrated in a combined infection of mice with murine cytomegalovirus (MCMV) and Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans. Mice infected intraperitoneally with a 0 to 20% lethal dose inoculum of MCMV 3 days prior to the intravenous injection of a 0 to 20% lethal dose inoculum of either the bacteria or fungus demonstrated a striking enhancement of mortality. MCMV-infected mice given Pseudomonas or Staphylococcus exhibited a 90 to 100% mortality within 24 to 48 h, whereas 80% of viral-infected animals injected with Candida died in 5 days. Injection of the bacteria or fungus at various times during the MCMV infection resulted in enhanced mortality on days 0,1,2, and 3 of the viral infection. Greatest synergism was observed on day 3, with a progressive decline in death rates thereafter. Immunization with MCMV abrogated the synergistic effect on mortality in all three combined infections. Immunization with Pseudomonas reduced mortality in the combined MCMV-Pseudomonas infection. These results indicate that mice exhibit a markedly enhanced susceptibility to bacterial and fungal infections during the course of the MCMV infection and suggest that the enhancement may be related to viral-induced alterations in host resistance."}
{"id": "PMID:186412", "title": "Clinical aspects of dental anomalies.", "content": "Many inherited disorders have oral manifestations which can be detected on dental radiographs as alterations in the morphology or chemical composition of the teeth. Thus the dentist may be the first to detect disorders of development and metabolism of importance to the general health of the patient and his family. In one group of conditions the pulp chamber is larger than normal. This may be associated with taurodontism in such conditions as polyploidy of the -X chromosome and trisomy-21 or Down's syndrome. Taurodontism also occurs in a variety of other syndromes including the tricho-dento-osseous syndrome described by Robinson, Miller and Worth (1966) and Mohr's syndrome. It may also be associated with scanty hair endoligodentia. In certain metabolic conditions the pulp chamber may be enlarged but the teeth are of relatively normal from (cynodont). Such cases include hypophosphatemic vitamin D-resistant and dependent rickets, pseudo-hypoparthyroidism otodental syndrome and hypophosphatasia. Small pulp chambers and associated anomalies of root morphology also occur in hereditary disorders either alone or as part of various syndromes such as dentino-osseous dysplasia and brackioskeletogenital syndrome. Dentinogenesis imperfecta may occur alone or as one manifestation of osteogenesis imperfecta. Other developmental defects including pulpal dysplasia, labodontia and dens invaginatus are also associated with small pulp chambers.", "contents": "Clinical aspects of dental anomalies. Many inherited disorders have oral manifestations which can be detected on dental radiographs as alterations in the morphology or chemical composition of the teeth. Thus the dentist may be the first to detect disorders of development and metabolism of importance to the general health of the patient and his family. In one group of conditions the pulp chamber is larger than normal. This may be associated with taurodontism in such conditions as polyploidy of the -X chromosome and trisomy-21 or Down's syndrome. Taurodontism also occurs in a variety of other syndromes including the tricho-dento-osseous syndrome described by Robinson, Miller and Worth (1966) and Mohr's syndrome. It may also be associated with scanty hair endoligodentia. In certain metabolic conditions the pulp chamber may be enlarged but the teeth are of relatively normal from (cynodont). Such cases include hypophosphatemic vitamin D-resistant and dependent rickets, pseudo-hypoparthyroidism otodental syndrome and hypophosphatasia. Small pulp chambers and associated anomalies of root morphology also occur in hereditary disorders either alone or as part of various syndromes such as dentino-osseous dysplasia and brackioskeletogenital syndrome. Dentinogenesis imperfecta may occur alone or as one manifestation of osteogenesis imperfecta. Other developmental defects including pulpal dysplasia, labodontia and dens invaginatus are also associated with small pulp chambers."}
{"id": "PMID:186413", "title": "Indomethacin enhancement of spleen-cell responsiveness to mitogen stimulation in tumorous mice.", "content": "Spleen cells removed from C57Bl/6J mice bearing a methylcholanthrene-induced fibrosarcoma (MC-16) demonstrate suppressed responsiveness of phytohemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) induced mitogenesis as compared to non-tumorous mice. A similar depression of PHA-induced mitogenesis was observed with spleen cells from C3H/HeJ mice bearing syngeneic mammary adenocarcinomas (C3HBA). The administration of indomethacin, a non-competitive irreversible prostaglandin (Pg) synthesis inhibitor, (75 or 100 mug/mouse, IP) on an alternate day basis to groups of tumor-bearing mice of both strains, significantly enhanced immune cell responsiveness to mitogenic stimulation. The addition of indomethacin (10 mug/ml) to cultures of spleen cells from these tumor-bearing mice, as well as to DBA/1J mice bearing the Cloudman S-91 melanoma, enhanced spleen-cell responsiveness to mitogen-induced DNA synthesis by as much as 156%. Indomethacin administration in vivo or in vitro had no significant effect on mitogen-induced DNA synthesis of spleen cells from non-tumor-bearing animals. It is hypothesized that tumors, or tumor-cell antigens, increase Pg production of a population of spleen cells, and that the increased Pg content of the spleen may be important in controlling immune responsiveness in mice.", "contents": "Indomethacin enhancement of spleen-cell responsiveness to mitogen stimulation in tumorous mice. Spleen cells removed from C57Bl/6J mice bearing a methylcholanthrene-induced fibrosarcoma (MC-16) demonstrate suppressed responsiveness of phytohemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) induced mitogenesis as compared to non-tumorous mice. A similar depression of PHA-induced mitogenesis was observed with spleen cells from C3H/HeJ mice bearing syngeneic mammary adenocarcinomas (C3HBA). The administration of indomethacin, a non-competitive irreversible prostaglandin (Pg) synthesis inhibitor, (75 or 100 mug/mouse, IP) on an alternate day basis to groups of tumor-bearing mice of both strains, significantly enhanced immune cell responsiveness to mitogenic stimulation. The addition of indomethacin (10 mug/ml) to cultures of spleen cells from these tumor-bearing mice, as well as to DBA/1J mice bearing the Cloudman S-91 melanoma, enhanced spleen-cell responsiveness to mitogen-induced DNA synthesis by as much as 156%. Indomethacin administration in vivo or in vitro had no significant effect on mitogen-induced DNA synthesis of spleen cells from non-tumor-bearing animals. It is hypothesized that tumors, or tumor-cell antigens, increase Pg production of a population of spleen cells, and that the increased Pg content of the spleen may be important in controlling immune responsiveness in mice."}
{"id": "PMID:186414", "title": "Expression of feline type-C virus in normal and tumor tissues of the domestic cat.", "content": "Tumor and normal tissues from domestic cats were examined for FeLV and RD-114 specific nucleic acids and proteins. Virus-positive tissues showed a 100- to 200-fold higher level of FeLV and a 200- to 400-fold higher level of FeLV p30 than virus-negative tumors and normal cat tissues. In contrast, the levels of RD-114 viral RNA and p30 antigen were comparable in the majority of tumorous and normal tissues examined. When the DNA of these tissues was examined for FeLV-related sequences, the virus-positive tumors were found to contain extra copies of FeLV DNA. Virus-negative tumors contained DNA sequences homologous with FeLV but the copy number of these sequences could not be distinguished from normal tissues. The results indicate that in certain FeLV-induced type-C lymphoproliferative diseases, extra type-C sequences not present in normal tissues can be identified.", "contents": "Expression of feline type-C virus in normal and tumor tissues of the domestic cat. Tumor and normal tissues from domestic cats were examined for FeLV and RD-114 specific nucleic acids and proteins. Virus-positive tissues showed a 100- to 200-fold higher level of FeLV and a 200- to 400-fold higher level of FeLV p30 than virus-negative tumors and normal cat tissues. In contrast, the levels of RD-114 viral RNA and p30 antigen were comparable in the majority of tumorous and normal tissues examined. When the DNA of these tissues was examined for FeLV-related sequences, the virus-positive tumors were found to contain extra copies of FeLV DNA. Virus-negative tumors contained DNA sequences homologous with FeLV but the copy number of these sequences could not be distinguished from normal tissues. The results indicate that in certain FeLV-induced type-C lymphoproliferative diseases, extra type-C sequences not present in normal tissues can be identified."}
{"id": "PMID:186415", "title": "Antibody responses to membrane antigens in monkeys infected with Herpesvirus saimiri.", "content": "The antibody response to Herpesvirus saimiri (HSV)-induced membrane antigens (MA) was followed in HSV-infected owl monkeys using the membrane immunofluorescence (MF) and antibody-dependent lymphocyte cytotoxicity (ADLC) assays. These responses were correlated with the loss of T-cell responsiveness to general mitogens. Antibody titers to MA as determined by ADLC but not MF increased to remarkably high titers in those monkeys that developed malignant disease following virus infection, while remaining at relatively low and constant levels in those monkeys that developed a chronic virus infection in the absence of malignant disease. This disease-related antibody response pattern was paralleled by the loss of T-cell function in diseased animals. The development of leukemia in HVS-infected owl monkeys did not suppress the ability of peripheral blood lymphocytes to act as effector cells in the ADLC assay. The relationship of these immune response patterns to the development of malignant disease in this system is discussed.", "contents": "Antibody responses to membrane antigens in monkeys infected with Herpesvirus saimiri. The antibody response to Herpesvirus saimiri (HSV)-induced membrane antigens (MA) was followed in HSV-infected owl monkeys using the membrane immunofluorescence (MF) and antibody-dependent lymphocyte cytotoxicity (ADLC) assays. These responses were correlated with the loss of T-cell responsiveness to general mitogens. Antibody titers to MA as determined by ADLC but not MF increased to remarkably high titers in those monkeys that developed malignant disease following virus infection, while remaining at relatively low and constant levels in those monkeys that developed a chronic virus infection in the absence of malignant disease. This disease-related antibody response pattern was paralleled by the loss of T-cell function in diseased animals. The development of leukemia in HVS-infected owl monkeys did not suppress the ability of peripheral blood lymphocytes to act as effector cells in the ADLC assay. The relationship of these immune response patterns to the development of malignant disease in this system is discussed."}
{"id": "PMID:186416", "title": "Undulating membraneous structures associated with the endoplasmic reticulum in tumour cells.", "content": "The morphology and occurrence of tubuloreticular and undulating membraneous structures (TRS and UMS) associated with the endoplasmic reticulum were examined under normal and pathologic conditions. It was concluded that TRS and UMS are cytoplasmic inclusions of similar type but of different organization. The occurrence of UMS in a human cell line derived from a carcinoma of the lung and in a transplantable chicken hepatoma derived from an MC-29 virus-induced liver tumour is described.", "contents": "Undulating membraneous structures associated with the endoplasmic reticulum in tumour cells. The morphology and occurrence of tubuloreticular and undulating membraneous structures (TRS and UMS) associated with the endoplasmic reticulum were examined under normal and pathologic conditions. It was concluded that TRS and UMS are cytoplasmic inclusions of similar type but of different organization. The occurrence of UMS in a human cell line derived from a carcinoma of the lung and in a transplantable chicken hepatoma derived from an MC-29 virus-induced liver tumour is described."}
{"id": "PMID:186417", "title": "Immunological monitoring and immunotherapy in carcinoma of the lung.", "content": "One hundred and seven patients with carcinoma of the lung underwent immunologic testing, and 62 of these patients were randomized to an immunotherapy protocol comparing the effects of Pasteur strain BCG, either alone or combined with allogeneic tumor cells, to the effects of no immunotherapy. Patients with residual disease left at the time of surgery or with metastatic disease at the time of diagnosis showed no increase in survival as a result of this form of immunotherapy. An insufficient number of patients with less advanced disease, in whom we would expect the most beneficial effect, have been entered in this study. In general, we were unable to document substantial effects of immunotherapy on the immunologic parameters tested. Only in recall antigen skin testing was there a statistically significant increase in reactivity in the immunotherapy groups. Tests of general immune status appeared to have a predictive value in monitoring lung cancer patients. Anergic patients had a poorer prognosis than did patients who demonstrated skin test reactivity. Patients with normal percentages of lymphocytes (T cells) forming rosettes with sheep erythrocytes at 29 degrees C were generally normal in other tests of immune competence. In serial studies of rosette formation, all patients who developed recurrent disease had a pattern of depressed or falling rosette values, and these abnormalities occurred an average of 3.1 months prior to clinical detection of recurrence. Patients with large-cell anaplastic carcinoma were found to have a significantly higher incidence of depressed rosette levels than the other histologic types. Both large and small-cell anaplastic patients had significantly depressed lymphocyte proliferation by mitogens and allogeneic cells. Although lung cancer patients have been described as immunologically depressed, they are capable of recognizing tumor-associated antigens. When tested in leukocyte migration inhibition assays with tumor-associated antigens, the majority of the patients in our study were found to be reactive. The use of a 3 M KCl extract of pleural effusion cells from a patient with pulmonary adenocarcinoma has given good reactivity and specificity in lung cancer patients of all histologic types. In addition, these patients have been shown to respond in a mixed lymphocyte/tumor interaction to tumor-associated antigens (Dean, 1976b).", "contents": "Immunological monitoring and immunotherapy in carcinoma of the lung. One hundred and seven patients with carcinoma of the lung underwent immunologic testing, and 62 of these patients were randomized to an immunotherapy protocol comparing the effects of Pasteur strain BCG, either alone or combined with allogeneic tumor cells, to the effects of no immunotherapy. Patients with residual disease left at the time of surgery or with metastatic disease at the time of diagnosis showed no increase in survival as a result of this form of immunotherapy. An insufficient number of patients with less advanced disease, in whom we would expect the most beneficial effect, have been entered in this study. In general, we were unable to document substantial effects of immunotherapy on the immunologic parameters tested. Only in recall antigen skin testing was there a statistically significant increase in reactivity in the immunotherapy groups. Tests of general immune status appeared to have a predictive value in monitoring lung cancer patients. Anergic patients had a poorer prognosis than did patients who demonstrated skin test reactivity. Patients with normal percentages of lymphocytes (T cells) forming rosettes with sheep erythrocytes at 29 degrees C were generally normal in other tests of immune competence. In serial studies of rosette formation, all patients who developed recurrent disease had a pattern of depressed or falling rosette values, and these abnormalities occurred an average of 3.1 months prior to clinical detection of recurrence. Patients with large-cell anaplastic carcinoma were found to have a significantly higher incidence of depressed rosette levels than the other histologic types. Both large and small-cell anaplastic patients had significantly depressed lymphocyte proliferation by mitogens and allogeneic cells. Although lung cancer patients have been described as immunologically depressed, they are capable of recognizing tumor-associated antigens. When tested in leukocyte migration inhibition assays with tumor-associated antigens, the majority of the patients in our study were found to be reactive. The use of a 3 M KCl extract of pleural effusion cells from a patient with pulmonary adenocarcinoma has given good reactivity and specificity in lung cancer patients of all histologic types. In addition, these patients have been shown to respond in a mixed lymphocyte/tumor interaction to tumor-associated antigens (Dean, 1976b)."}
{"id": "PMID:186418", "title": "Studies on the microcytotoxicity test. I. Evidence that the effects of normal lymphoid cells on tumour cell growth in microtest plates may be caused by non-immunological modifications of the culture medium.", "content": "Lymph node cells from normal Wistar rats were found to affect the growth/survival of syngeneic chemically-induced solid tumour cells in the microcytotoxicity test. Whether inhibition or enhancement of tumour cell numbers occurred depended on the particular tumour cell type and, in some cases, on the particular in vitro subline used. Fractionation of LNC on nylon wool columns revealed that the two effects were mediated by distinct subpopulations of lymphoid cells: column-retained cells showed predominantly an inhibitory effect and column-eluted cells predominantly an enhancing effect. When column-retained and column-eluted cells were cultured under the conditions of the microcytotoxicity test but in the absence of tumour cell growth. The inhibitory activity was maximal within one hour of lymphocyte culture, while the enhancing effect developed slowly during incubation. Furthermore, the tumour cells themselves were found to produce growth-enhancing activity. It is proposed that interaction between these various supernatant activities accounts at least in part for the non-specific effects of normal lymphoid cells in the microcytotoxicity test.", "contents": "Studies on the microcytotoxicity test. I. Evidence that the effects of normal lymphoid cells on tumour cell growth in microtest plates may be caused by non-immunological modifications of the culture medium. Lymph node cells from normal Wistar rats were found to affect the growth/survival of syngeneic chemically-induced solid tumour cells in the microcytotoxicity test. Whether inhibition or enhancement of tumour cell numbers occurred depended on the particular tumour cell type and, in some cases, on the particular in vitro subline used. Fractionation of LNC on nylon wool columns revealed that the two effects were mediated by distinct subpopulations of lymphoid cells: column-retained cells showed predominantly an inhibitory effect and column-eluted cells predominantly an enhancing effect. When column-retained and column-eluted cells were cultured under the conditions of the microcytotoxicity test but in the absence of tumour cell growth. The inhibitory activity was maximal within one hour of lymphocyte culture, while the enhancing effect developed slowly during incubation. Furthermore, the tumour cells themselves were found to produce growth-enhancing activity. It is proposed that interaction between these various supernatant activities accounts at least in part for the non-specific effects of normal lymphoid cells in the microcytotoxicity test."}
{"id": "PMID:186419", "title": "Expression of viral proteins in mammalian cells transformed by avian sarcoma viruses.", "content": "The expression of viral proteins in nine lines of hamster and rat cells transformed by avian sarcoma viruses (ASV) was studied by indirect immunofluorescence with monospecific antisera to purified gp85 and p27 of AMV-B and a polyvalent antiserum to all the p proteins of this same virus. The lines of ASV-transformed cells were either low virus producers (VP) or inducible or non-inducible non producers (NP). Cytoplasmic expression of p proteins was observed in all the cell lines except the least inducible NP cell line, and cytoplasmic expression of gp85 in all the cell lines. The degree of expression varied widely with the lines and was not related to the class of permissiveness or inducibility. However, in the inducible NP class, the expression of p proteins and gp85 was higher in the most inducible cell lines. The data also suggest that the expression of the p proteins must be uncoordinate in at least some cell lines and must also be uncoordinate with the expression of gp85. In the VP cell lines and the most inducible NP lines, g85 and some p proteins other than p27 were also expressed on the cell membrane. The membrane expression of gp85 and the p proteins which were expressed appeared to be coordinate and to parallel the degree of cytoplasmic expression. In contrast, no, or a negligible expression of viral proteins was observed on the membrane of the least inducible and the non-inducible cell lines. These results suggest that there may exist translational and/or post-translational controls of the expression of viral proteins in the ASV-transformed mammalian cells and that the permissiveness and the inducibility of the cells may depend on the insertion of viral proteins in the cell membrane. The failure of p27 to insert in the cell membrane could account for the low permissiveness or the non-permissiveness of the cells.", "contents": "Expression of viral proteins in mammalian cells transformed by avian sarcoma viruses. The expression of viral proteins in nine lines of hamster and rat cells transformed by avian sarcoma viruses (ASV) was studied by indirect immunofluorescence with monospecific antisera to purified gp85 and p27 of AMV-B and a polyvalent antiserum to all the p proteins of this same virus. The lines of ASV-transformed cells were either low virus producers (VP) or inducible or non-inducible non producers (NP). Cytoplasmic expression of p proteins was observed in all the cell lines except the least inducible NP cell line, and cytoplasmic expression of gp85 in all the cell lines. The degree of expression varied widely with the lines and was not related to the class of permissiveness or inducibility. However, in the inducible NP class, the expression of p proteins and gp85 was higher in the most inducible cell lines. The data also suggest that the expression of the p proteins must be uncoordinate in at least some cell lines and must also be uncoordinate with the expression of gp85. In the VP cell lines and the most inducible NP lines, g85 and some p proteins other than p27 were also expressed on the cell membrane. The membrane expression of gp85 and the p proteins which were expressed appeared to be coordinate and to parallel the degree of cytoplasmic expression. In contrast, no, or a negligible expression of viral proteins was observed on the membrane of the least inducible and the non-inducible cell lines. These results suggest that there may exist translational and/or post-translational controls of the expression of viral proteins in the ASV-transformed mammalian cells and that the permissiveness and the inducibility of the cells may depend on the insertion of viral proteins in the cell membrane. The failure of p27 to insert in the cell membrane could account for the low permissiveness or the non-permissiveness of the cells."}
{"id": "PMID:186420", "title": "Properties of a baboon lymphotropic herpesvirus related to Epstein-Barr virus.", "content": "Three lymphoblastoid cell lines were established from splenic lymphocytes of a lymphomatous baboon (Papio hamadryas) by co-cultivation of the lymphocytes with X-irradiated cells of marmoset or baboon lymphoblastoid cell cultures; the baboon splenic lymphocytes failed to grow when cultured alone. A herpesvirus, associated with each cell line, was identified by immunofluorescence, molecular hybridization and electron microscopy. Antigenic comparison with Epstein-Barr virus (EBV) showed that the baboon herpesvirus and EBV shared cross-reacting viral capsid antigens (VCA): 20 of 20 (100%) anti-VCA (EBV)-positive human sera and 55 of 62 (89%) baboon sera reacted with the baboon lymphoblastoid cells and baboon sera stained EBV VCA in P3HR-1 and EB-3 cells. No nuclear antigen, as assayed by anti-complement immunofluorescence tests, was detected in baboon lymphoblastoid cells when human or baboon anti-VCA positive sera were used. Baboon anti-VCA-positive sera also failed to stain EBV nuclear antigens (EBNA) in Raji or P3HR-1 cells. Preliminary molecular hybridization studies showed only approximately 40% homology between viral DNA of baboon cell lines and DNA of EBV derived from P3HR-1 cells.", "contents": "Properties of a baboon lymphotropic herpesvirus related to Epstein-Barr virus. Three lymphoblastoid cell lines were established from splenic lymphocytes of a lymphomatous baboon (Papio hamadryas) by co-cultivation of the lymphocytes with X-irradiated cells of marmoset or baboon lymphoblastoid cell cultures; the baboon splenic lymphocytes failed to grow when cultured alone. A herpesvirus, associated with each cell line, was identified by immunofluorescence, molecular hybridization and electron microscopy. Antigenic comparison with Epstein-Barr virus (EBV) showed that the baboon herpesvirus and EBV shared cross-reacting viral capsid antigens (VCA): 20 of 20 (100%) anti-VCA (EBV)-positive human sera and 55 of 62 (89%) baboon sera reacted with the baboon lymphoblastoid cells and baboon sera stained EBV VCA in P3HR-1 and EB-3 cells. No nuclear antigen, as assayed by anti-complement immunofluorescence tests, was detected in baboon lymphoblastoid cells when human or baboon anti-VCA positive sera were used. Baboon anti-VCA-positive sera also failed to stain EBV nuclear antigens (EBNA) in Raji or P3HR-1 cells. Preliminary molecular hybridization studies showed only approximately 40% homology between viral DNA of baboon cell lines and DNA of EBV derived from P3HR-1 cells."}
{"id": "PMID:186421", "title": "Leukemogenic activity of murine type C viruses after long-term passage in vitro.", "content": "Cloned stocks of several murine leukemia viruses (MuLVs) were shown to be leukemogenic for susceptible mice after more than nine years of in vitro passaging in mouse embryo fibroblasts. Tissue culture-grown Rauscher (R-) MuLVs injected into newborn or young adult BALB/c mice induced lymphocytic leukemias in 100% of the animals beginning 80 days post-inoculation. No erythroblastic leukemia was observed even after passaging the tissue-culture-grown R-MuLVs twice through mice, indicating that the component responsible for that disease had been lost or attenuated during growth in fibroblasts. The tissue-culture-grown stock of Moloney (M-) MuLVs likewise induced lymphocytic leukemias in 94% of injected newborn BALB/c mice, and the tissue culture-grown Gross (G-) MuLVs induced lymphocytic leukemias in 42% of injected newborn C3Hf mice. The host range and neutralization characteristics of viruses recovered from animals that became leukemic after injection with the tissue-culture-maintained MuLVs were found to be identical with those of the injected viruses. These data implicate the injected MuLVs in the induction of the leukemias and suggest that the capacity to induce the disease is stably inherited as part of the viral genome even in the absence of expression.", "contents": "Leukemogenic activity of murine type C viruses after long-term passage in vitro. Cloned stocks of several murine leukemia viruses (MuLVs) were shown to be leukemogenic for susceptible mice after more than nine years of in vitro passaging in mouse embryo fibroblasts. Tissue culture-grown Rauscher (R-) MuLVs injected into newborn or young adult BALB/c mice induced lymphocytic leukemias in 100% of the animals beginning 80 days post-inoculation. No erythroblastic leukemia was observed even after passaging the tissue-culture-grown R-MuLVs twice through mice, indicating that the component responsible for that disease had been lost or attenuated during growth in fibroblasts. The tissue-culture-grown stock of Moloney (M-) MuLVs likewise induced lymphocytic leukemias in 94% of injected newborn BALB/c mice, and the tissue culture-grown Gross (G-) MuLVs induced lymphocytic leukemias in 42% of injected newborn C3Hf mice. The host range and neutralization characteristics of viruses recovered from animals that became leukemic after injection with the tissue-culture-maintained MuLVs were found to be identical with those of the injected viruses. These data implicate the injected MuLVs in the induction of the leukemias and suggest that the capacity to induce the disease is stably inherited as part of the viral genome even in the absence of expression."}
{"id": "PMID:186422", "title": "Adrenocorticotropin. 48. Synthesis and biological activity of (15, 16-D-lysine, 17, 18-D-arginine)-adrenocorticotropin-(1-19) and an all-D-retropeptide related to the amino terminal octadecapeptide of adrenocorticotropin.", "content": "The peptide [15, 16-D-lysine, 17, 18-D-arginine]-adrenocorticotropin-(1-19) and an all-D-retropeptide related to the amino terminal octadecapeptide of adrenocorticotropin have been synthesized by the solid-phase method. The nonadecapeptide was shown to possess 10-15% of the steroidogenic activity and 3% of the lipolytic activity of adrenocorticotropin-(1-19). The all-D-retropeptide showed no activity and exhibited no inhibitory activity in steroidogenesis and lipolysis.", "contents": "Adrenocorticotropin. 48. Synthesis and biological activity of (15, 16-D-lysine, 17, 18-D-arginine)-adrenocorticotropin-(1-19) and an all-D-retropeptide related to the amino terminal octadecapeptide of adrenocorticotropin. The peptide [15, 16-D-lysine, 17, 18-D-arginine]-adrenocorticotropin-(1-19) and an all-D-retropeptide related to the amino terminal octadecapeptide of adrenocorticotropin have been synthesized by the solid-phase method. The nonadecapeptide was shown to possess 10-15% of the steroidogenic activity and 3% of the lipolytic activity of adrenocorticotropin-(1-19). The all-D-retropeptide showed no activity and exhibited no inhibitory activity in steroidogenesis and lipolysis."}
{"id": "PMID:186423", "title": "X-ray-induced luminescence and optical absorption in DNA films.", "content": "For DNA films, X-irradiated at 77 K, a comparative study was performed on (a) light emission (fluorescence and phosphorescence) during irradiation, (b) afterglow and thermoluminescence, (c) optical absorption after irradiation, and (d) free-radical reactions in similar gamma-irradiatied DNA samples. Spectra are reported for the various kinds of light emission and for the optical absorption. From temperature-dependence studies, it was concluded that the light-emission phenomena are unrelated to the reactions of the free radicals as studied by electron paramagnetic resonance. The optical absorption on the other hand, is strongly correlated to the presence of free radicals in the DNA. Some mechanisms possibly involved in the observed luminescence reactions are discussed.", "contents": "X-ray-induced luminescence and optical absorption in DNA films. For DNA films, X-irradiated at 77 K, a comparative study was performed on (a) light emission (fluorescence and phosphorescence) during irradiation, (b) afterglow and thermoluminescence, (c) optical absorption after irradiation, and (d) free-radical reactions in similar gamma-irradiatied DNA samples. Spectra are reported for the various kinds of light emission and for the optical absorption. From temperature-dependence studies, it was concluded that the light-emission phenomena are unrelated to the reactions of the free radicals as studied by electron paramagnetic resonance. The optical absorption on the other hand, is strongly correlated to the presence of free radicals in the DNA. Some mechanisms possibly involved in the observed luminescence reactions are discussed."}
{"id": "PMID:186424", "title": "Radical formation in salts of pyrimidines III. Cytosine . H2O cyrstals.", "content": "The radicals produced by X-irradiation at 77 K and at 300 K in cytosine monohydrate crystals have been analysed by electron-spin-resonance (e.s.r.) spectroscopy. Three radicals have been identified at 77 K: the anion radical and the cation radical of the cytosine molecule, together with the radical resutling from H-abstraction from the nitrogen N1. Irradiation at 300 K produces radicals resulting from H-adition at three different positions of the cytosine molecule. These are the C5-addition radical, the C6-addition radical, and the O2-addition radical. The results are compared with those found previously by other authors.", "contents": "Radical formation in salts of pyrimidines III. Cytosine . H2O cyrstals. The radicals produced by X-irradiation at 77 K and at 300 K in cytosine monohydrate crystals have been analysed by electron-spin-resonance (e.s.r.) spectroscopy. Three radicals have been identified at 77 K: the anion radical and the cation radical of the cytosine molecule, together with the radical resutling from H-abstraction from the nitrogen N1. Irradiation at 300 K produces radicals resulting from H-adition at three different positions of the cytosine molecule. These are the C5-addition radical, the C6-addition radical, and the O2-addition radical. The results are compared with those found previously by other authors."}
{"id": "PMID:186431", "title": "Experimental disciform edema and necrotizing keratitis in the rabbit.", "content": "The development of experimental disciform edema and necrotizing keratitis in the corneas or rabbits following intrastromal inoculation with the RE strain of herpes simplex virus is described. Following an initial episode of conjunctivitis and epithelial keratitis, a mild, centrally localized, stromal edema developed on the fifth day. Stromal edema, opcification, and neovascularization of the cornea reached maximum severity on the seventh to twenty-second day, and began to fade in most eyes thereafter. On the twenty-ninth day most corneas have attained a resolved state characterized by subepithelial granular opacities. Several eyes were observed which developed central necrotizing keratitis. Marked similarities between the animal model and human herpetic stromal keratitis were apparent. Histological observations show that early necrotizing keratitis in the rabbit is characterized by an infiltration of plasma cells and lymphocytes in the limbus, with polymorphonuclear leukocytes, lymphocytes, and macrophages in the central cornea.", "contents": "Experimental disciform edema and necrotizing keratitis in the rabbit. The development of experimental disciform edema and necrotizing keratitis in the corneas or rabbits following intrastromal inoculation with the RE strain of herpes simplex virus is described. Following an initial episode of conjunctivitis and epithelial keratitis, a mild, centrally localized, stromal edema developed on the fifth day. Stromal edema, opcification, and neovascularization of the cornea reached maximum severity on the seventh to twenty-second day, and began to fade in most eyes thereafter. On the twenty-ninth day most corneas have attained a resolved state characterized by subepithelial granular opacities. Several eyes were observed which developed central necrotizing keratitis. Marked similarities between the animal model and human herpetic stromal keratitis were apparent. Histological observations show that early necrotizing keratitis in the rabbit is characterized by an infiltration of plasma cells and lymphocytes in the limbus, with polymorphonuclear leukocytes, lymphocytes, and macrophages in the central cornea."}
{"id": "PMID:186432", "title": "Differences in adenylate cyclase activities in murine normal cells and bladder tumor cells in tissue culture.", "content": "Cyclic AMP may be involved in the modulation of cell growth. The present work sought to further define differences between normal cells and tumor cells in their cyclic AMP system. Mouse embryo fibroblasts and murine bladder transitional epithelium tumor cells were grown in vitro; at various times, adenyl cyclase activity was assayed by measuring the conversion of [alpha32P]ATP to cyclic AM32P; stimulation by prostaglandin E1 or sodium fluoride was also determined. Base line and fluoride-stimulated enzyme activity were significantly greater in normal cells than tumor cells (P less than 0.01), and reached a peak at day 2; at confluency, levels in both systems decreased. Prostaglandin E1-stimulated levels, in contrast, were greater in tumor cells, there being a 10 fold greater relative stimulation in these cells compared to normal cells (P less than 0.01). Findings of a possibly greater sensitivity in these tumor cells may be important in a therapeutic modulation of tumor growth.", "contents": "Differences in adenylate cyclase activities in murine normal cells and bladder tumor cells in tissue culture. Cyclic AMP may be involved in the modulation of cell growth. The present work sought to further define differences between normal cells and tumor cells in their cyclic AMP system. Mouse embryo fibroblasts and murine bladder transitional epithelium tumor cells were grown in vitro; at various times, adenyl cyclase activity was assayed by measuring the conversion of [alpha32P]ATP to cyclic AM32P; stimulation by prostaglandin E1 or sodium fluoride was also determined. Base line and fluoride-stimulated enzyme activity were significantly greater in normal cells than tumor cells (P less than 0.01), and reached a peak at day 2; at confluency, levels in both systems decreased. Prostaglandin E1-stimulated levels, in contrast, were greater in tumor cells, there being a 10 fold greater relative stimulation in these cells compared to normal cells (P less than 0.01). Findings of a possibly greater sensitivity in these tumor cells may be important in a therapeutic modulation of tumor growth."}
{"id": "PMID:186434", "title": "In vitro stimulation of human lymphocytes by purified cytomegalovirus.", "content": "Lymphocytes from 19 healthy donors were tested against purified cytomegalovirus (CMV) strain Ad 169, in a lymphocyte-transformation test. The test was performed in microcultures using various preparations and concentrations of antigen. These included, besides purified CMV, CMV-infected cells, herpes simplex virus type 1 antigen, and control antigens. Lymphocytes from CMV-seropositive donors were stimulated by purified virus and infected cells, whereas lymphocytes from seronegative donors did not respond. Similarly, only lymphocytes from herpes-seropositive donors did respond to herpes antigen. With these preparations of antigen the test was found to be sensitive and specific.", "contents": "In vitro stimulation of human lymphocytes by purified cytomegalovirus. Lymphocytes from 19 healthy donors were tested against purified cytomegalovirus (CMV) strain Ad 169, in a lymphocyte-transformation test. The test was performed in microcultures using various preparations and concentrations of antigen. These included, besides purified CMV, CMV-infected cells, herpes simplex virus type 1 antigen, and control antigens. Lymphocytes from CMV-seropositive donors were stimulated by purified virus and infected cells, whereas lymphocytes from seronegative donors did not respond. Similarly, only lymphocytes from herpes-seropositive donors did respond to herpes antigen. With these preparations of antigen the test was found to be sensitive and specific."}
{"id": "PMID:186433", "title": "Plaque dissociation of herpes simplex viruses: biochemical and biological characters of the viral variants.", "content": "Polycaryocytogenic (P) and non-polycaryocytogenic, or aggregating (A), stable variants were selected from a herpes simplex virus type 1 (HSV-1) and from a herpes simplex virus type 2 (HSV 2) which had not been deliberately exposed to known mutagenic agents. The P variant of HSV-1 (FP) differed from the A variant (FA) in polypeptides and glycoprotein patterns, but no gross differences were evident between the two variants of HSV-2 (GP and GA). Each P variant proved more 'specific' than each A variant in immune neutralization tests. At high multiplicity, GP produced polycaryocytes but FP did not. Virulence tests in mice showed FP to be much more virulent than FA but GA to be more virulent than GP. Finally, A and P variants of each type could not be differentiated with respect to thermal resistance of virons, capacity to grow at high temperature, and buoyant density of DNA.", "contents": "Plaque dissociation of herpes simplex viruses: biochemical and biological characters of the viral variants. Polycaryocytogenic (P) and non-polycaryocytogenic, or aggregating (A), stable variants were selected from a herpes simplex virus type 1 (HSV-1) and from a herpes simplex virus type 2 (HSV 2) which had not been deliberately exposed to known mutagenic agents. The P variant of HSV-1 (FP) differed from the A variant (FA) in polypeptides and glycoprotein patterns, but no gross differences were evident between the two variants of HSV-2 (GP and GA). Each P variant proved more 'specific' than each A variant in immune neutralization tests. At high multiplicity, GP produced polycaryocytes but FP did not. Virulence tests in mice showed FP to be much more virulent than FA but GA to be more virulent than GP. Finally, A and P variants of each type could not be differentiated with respect to thermal resistance of virons, capacity to grow at high temperature, and buoyant density of DNA."}
{"id": "PMID:186435", "title": "Genetic factors influencing endogenous type-C RNA viruses of mouse cells: control of viral polypeptide expression in the C57BL/10 strain.", "content": "Type-C viral polypeptides are expressed at very low levels in C57BL/10 liver and embryo cells as compared to cells of other mouse strains. The 12,000-mol. wt. polypeptide in C57BL/10 cells was purified and shown to possess type-specific antigenic determinants indistinguishable from those of a previously described class of endogenous virus. The very low levels of endogenous virus-specific RNA in cells of C57BL/10 as compared to other strains suggests control of this endogenous virus at the level of transcription. Analysis of viral antigen expression F1 hybrids of C57BL/10 with strains characterized by intermediate and high levels of viral antigen expression indicates that the restriction of this endogenous virus by C57BL/10 cells is not due to simple dominance by a repressor of virus expression.", "contents": "Genetic factors influencing endogenous type-C RNA viruses of mouse cells: control of viral polypeptide expression in the C57BL/10 strain. Type-C viral polypeptides are expressed at very low levels in C57BL/10 liver and embryo cells as compared to cells of other mouse strains. The 12,000-mol. wt. polypeptide in C57BL/10 cells was purified and shown to possess type-specific antigenic determinants indistinguishable from those of a previously described class of endogenous virus. The very low levels of endogenous virus-specific RNA in cells of C57BL/10 as compared to other strains suggests control of this endogenous virus at the level of transcription. Analysis of viral antigen expression F1 hybrids of C57BL/10 with strains characterized by intermediate and high levels of viral antigen expression indicates that the restriction of this endogenous virus by C57BL/10 cells is not due to simple dominance by a repressor of virus expression."}
{"id": "PMID:186437", "title": "Inhibition of herpes simplex virus multiplication by 2,3-bis(acetyl mercaptomethyl)-quinoxalin.", "content": "The drug 2,3-bis(acetyl mercaptomethyl)-quinoxalin (BAMMQ) was 99.9% inhibitory for herpes simplex virus (HSV) multiplication in cell cultures at concentrations of 1.6 X 10(-5) M or less. The drug was not inactivating for the virus, did not interfere with adsorption and penetration of the virus, and was still active when added as late as 12 h after infection with HSV. BAMMQ did not prevent HSV DNA replication, but interfered with a late stage of virus assembly and/or maturation.", "contents": "Inhibition of herpes simplex virus multiplication by 2,3-bis(acetyl mercaptomethyl)-quinoxalin. The drug 2,3-bis(acetyl mercaptomethyl)-quinoxalin (BAMMQ) was 99.9% inhibitory for herpes simplex virus (HSV) multiplication in cell cultures at concentrations of 1.6 X 10(-5) M or less. The drug was not inactivating for the virus, did not interfere with adsorption and penetration of the virus, and was still active when added as late as 12 h after infection with HSV. BAMMQ did not prevent HSV DNA replication, but interfered with a late stage of virus assembly and/or maturation."}
{"id": "PMID:186436", "title": "An unusual defective genotype derived from herpes simplex virus strain ANG.", "content": "A defective genotype of herpes simplex virus strain Angelotti (HSV ANG) accumulates in the course of controlled serial high MOI virus passages representing 50-60% of the total number of mature virions in the seventh of these passages. Defective HSV ANG significantly differs from other defective HSV genotypes described so far: the DNA of the defective particles has the same buoyant density as nondefective DNA. In contrast to non-defective HSV ANG DNA, it is not attacked by the restriction endonucleases Eco R I, Hpa I and Hind III. Defective virions strongly suppress the formation of progeny virus. They do not interfere, however, with the synthesis of HSV-specified thymidine (TdR) kinase.", "contents": "An unusual defective genotype derived from herpes simplex virus strain ANG. A defective genotype of herpes simplex virus strain Angelotti (HSV ANG) accumulates in the course of controlled serial high MOI virus passages representing 50-60% of the total number of mature virions in the seventh of these passages. Defective HSV ANG significantly differs from other defective HSV genotypes described so far: the DNA of the defective particles has the same buoyant density as nondefective DNA. In contrast to non-defective HSV ANG DNA, it is not attacked by the restriction endonucleases Eco R I, Hpa I and Hind III. Defective virions strongly suppress the formation of progeny virus. They do not interfere, however, with the synthesis of HSV-specified thymidine (TdR) kinase."}
{"id": "PMID:186442", "title": "[Scintigraphic findings of liver and spleen in dermatomyositis].", "content": "In 3 patients with dermatomyositis scintigraphic examination of liver and spleen revealed in every case diseases of the liver such as hepatoma, hepatomegaly and damage of the liver parenchyma. Therefore scintigraphic examination of liver and spleen in patients with dermatomyositis is suggested to exclude primary or secondary affections of these organs.", "contents": "[Scintigraphic findings of liver and spleen in dermatomyositis]. In 3 patients with dermatomyositis scintigraphic examination of liver and spleen revealed in every case diseases of the liver such as hepatoma, hepatomegaly and damage of the liver parenchyma. Therefore scintigraphic examination of liver and spleen in patients with dermatomyositis is suggested to exclude primary or secondary affections of these organs."}
{"id": "PMID:186438", "title": "Immune inhibition of virus release from herpes simplex virus-infected cells.", "content": "By treatment of herpes simplex virus-infected cells with virus antiserum with or without complement, the yield of infectious extracellular virus was significantly reduced. This was shown to be due to an immune alteration of the cell membrane which inhibited release of virus particles from the infected cells and not due to neutralization; both type-common and type-specific antigens of herpes simplex virus were involved. The phenomenon was also evident with antisera directed against cell determinants. The experimental findings are presented and their significance in the immunological defense mechanisms of the body and in viral immunotherapy is discussed.", "contents": "Immune inhibition of virus release from herpes simplex virus-infected cells. By treatment of herpes simplex virus-infected cells with virus antiserum with or without complement, the yield of infectious extracellular virus was significantly reduced. This was shown to be due to an immune alteration of the cell membrane which inhibited release of virus particles from the infected cells and not due to neutralization; both type-common and type-specific antigens of herpes simplex virus were involved. The phenomenon was also evident with antisera directed against cell determinants. The experimental findings are presented and their significance in the immunological defense mechanisms of the body and in viral immunotherapy is discussed."}
{"id": "PMID:186443", "title": "Some histochemical studies on the prostate, urethral and bulbourethral glands of the one-humped camel (Camelus dromedarius).", "content": "The histochemical localization of carbohydrates, ribonucleoproteins (RNA), lipids, some hydrolytic enzymes, succinate and lactate dehydrogenase and acetylcholinesterase were investigated in the prostate, urethral and bulbourethral glands of the camel. These glands probably secrete carbohydrate-protein complexes. In the bulbourethral glands, they are sulphated mucopolysaccharides. RNA was seen in the cytoplasm of the prostate and urethral glands. Neutral lipids were cytoplasmic and present in moderate amounts in the prostate and urethral glands and in traces, in the bulbourethral gland. Acid phosphatase-containing granules were abundant in the prostate, moderate in the urethral glands and in traces in the bulbourethral glands. Alkaline phosphatase was observed in the apical cytoplasm of the prostate and bulbourethral glands and in the ducts of the urethral glands. ATPase and adenosine 5-monophosphatase were seen in the basal laminae and interstitial tissue. In the urethral glands, adenosine 5-monophosphatase was distributed diffusely in the cytoplasm. Succinate dehydrogenase was seen in the urethral and bulbourethral glands. Varying degrees of lactate dehydrogenase activity was observed in all the glands. Acetylcholinesterase was confined to neural elements. The pars disseminata and the urethral glands were considered as two distinct glandular zones along the pelvic urethra. The significance of these histochemical results is discussed.", "contents": "Some histochemical studies on the prostate, urethral and bulbourethral glands of the one-humped camel (Camelus dromedarius). The histochemical localization of carbohydrates, ribonucleoproteins (RNA), lipids, some hydrolytic enzymes, succinate and lactate dehydrogenase and acetylcholinesterase were investigated in the prostate, urethral and bulbourethral glands of the camel. These glands probably secrete carbohydrate-protein complexes. In the bulbourethral glands, they are sulphated mucopolysaccharides. RNA was seen in the cytoplasm of the prostate and urethral glands. Neutral lipids were cytoplasmic and present in moderate amounts in the prostate and urethral glands and in traces, in the bulbourethral gland. Acid phosphatase-containing granules were abundant in the prostate, moderate in the urethral glands and in traces in the bulbourethral glands. Alkaline phosphatase was observed in the apical cytoplasm of the prostate and bulbourethral glands and in the ducts of the urethral glands. ATPase and adenosine 5-monophosphatase were seen in the basal laminae and interstitial tissue. In the urethral glands, adenosine 5-monophosphatase was distributed diffusely in the cytoplasm. Succinate dehydrogenase was seen in the urethral and bulbourethral glands. Varying degrees of lactate dehydrogenase activity was observed in all the glands. Acetylcholinesterase was confined to neural elements. The pars disseminata and the urethral glands were considered as two distinct glandular zones along the pelvic urethra. The significance of these histochemical results is discussed."}
{"id": "PMID:186439", "title": "Agarose gel filtration of concentrated fecal extracts containing virus-like particles associated with hepatitis A.", "content": "Virus-like particles shown to be associated with hepatitis A infection were recently visualized by immune electron microscopy in human and chimpanzee acute-phase fecal extracts. Agarose gel filtration of concentrated chimpanzee fecal extracts containing those 27-nm diameter particles separated more than 99% of the high molecular weight fecal impurities into two major peaks as determined by absorbance at 280 and 260 nm. The hepatitis A-associated particles were found between these two peaks by both immune electron microscopy and a new immunoradiometric assay.", "contents": "Agarose gel filtration of concentrated fecal extracts containing virus-like particles associated with hepatitis A. Virus-like particles shown to be associated with hepatitis A infection were recently visualized by immune electron microscopy in human and chimpanzee acute-phase fecal extracts. Agarose gel filtration of concentrated chimpanzee fecal extracts containing those 27-nm diameter particles separated more than 99% of the high molecular weight fecal impurities into two major peaks as determined by absorbance at 280 and 260 nm. The hepatitis A-associated particles were found between these two peaks by both immune electron microscopy and a new immunoradiometric assay."}
{"id": "PMID:186444", "title": "Contact-mediated changes in ATPase activity at the surface of primary cultured hepatoma cells.", "content": "Hepatoma cells grown in monolayer culture display certain alterations in their Mg-ATPase activity present on the cell surface as a function of time during a exponential growth. Levels of enzyme estimated biochemically and expressed as activity per cell increase as the cell population density increases. Histochemical investigation shows that Mg-ATPase activity is located intensively on the surface of cell contact and the activity is not encountered on the cell surface facing the free space. No enzyme activity is detected histochemically on the cell surface of sparse culture. Deposits of acidic polysaccharide are also seen on the surface of cell contact.", "contents": "Contact-mediated changes in ATPase activity at the surface of primary cultured hepatoma cells. Hepatoma cells grown in monolayer culture display certain alterations in their Mg-ATPase activity present on the cell surface as a function of time during a exponential growth. Levels of enzyme estimated biochemically and expressed as activity per cell increase as the cell population density increases. Histochemical investigation shows that Mg-ATPase activity is located intensively on the surface of cell contact and the activity is not encountered on the cell surface facing the free space. No enzyme activity is detected histochemically on the cell surface of sparse culture. Deposits of acidic polysaccharide are also seen on the surface of cell contact."}
{"id": "PMID:186440", "title": "Serologic comparison of hepatitis A antigen to echovirus 25 isolate CR69(076) recovered from a patient with viral hepatitis.", "content": "A serologic comparison was performed by immune electron microscopy between hepatitis A antigen (related to the MS-1 strain of hepatitis A virus) and a viral isolate, CR69(076), from the stool of a patient in Costa Rica with viral hepatitis. CR69(076) was not antigenically related to hepatitis A antigen but was related to echovirus 25. Thus, it is unrelated to the MS-1 strain of hepatitis A virus.", "contents": "Serologic comparison of hepatitis A antigen to echovirus 25 isolate CR69(076) recovered from a patient with viral hepatitis. A serologic comparison was performed by immune electron microscopy between hepatitis A antigen (related to the MS-1 strain of hepatitis A virus) and a viral isolate, CR69(076), from the stool of a patient in Costa Rica with viral hepatitis. CR69(076) was not antigenically related to hepatitis A antigen but was related to echovirus 25. Thus, it is unrelated to the MS-1 strain of hepatitis A virus."}
{"id": "PMID:186448", "title": "Rapid eye movement (REM) activity in normal and autistic children during REM sleep.", "content": "Thirty normal children (aged 3--68 months) and 16 autistic children (aged 36--62 months) were recorded during nonmedicated sleep and data pertaining to rapid eye movements (REM) were measured during the first three REM periods of the night. When time of night from which data were gathered was held constant, normal children showed a significant relationship between age and the organization of eye movements into discrete bursts. When autistic children were compared to age-matched normal controls, they showed an immaturity in this phenomena, their results being similar to those found in children less than 18 months of age. Such an immaturity could result from dysfunction at a number of diverse levels and sites in the central nervous system.", "contents": "Rapid eye movement (REM) activity in normal and autistic children during REM sleep. Thirty normal children (aged 3--68 months) and 16 autistic children (aged 36--62 months) were recorded during nonmedicated sleep and data pertaining to rapid eye movements (REM) were measured during the first three REM periods of the night. When time of night from which data were gathered was held constant, normal children showed a significant relationship between age and the organization of eye movements into discrete bursts. When autistic children were compared to age-matched normal controls, they showed an immaturity in this phenomena, their results being similar to those found in children less than 18 months of age. Such an immaturity could result from dysfunction at a number of diverse levels and sites in the central nervous system."}
{"id": "PMID:186449", "title": "Fosfomycin resistance: selection method for internal and extended deletions of the phosphoenolpyruvate:sugar phosphotransferase genes of Salmonella typhimurium.", "content": "Selection for resistance to the antibiotic fosfomycin (FOS; L-cis 1,2-epoxypropylphosphonic acid, a structural analogue of phosphoenolpyruvate) was used to isolate mutants carrying internal and extended deletions of varying lengths within the ptsHI operon of Salmonella typhimurium. Strains carrying \"tight\" ptsI point mutations and all mutants in which some or all of the ptsI gene was deleted were FOS resistant. In contrast, strains carrying ptsH point mutations were sensitive to FOS. Resistance to FOS appeared to result indirectly from catabolite repression of an FOS transport system, probably the sn-glycerol-3-phosphate transport system. Resistant ptsI mutants became sensitive to FOS when grown on D-glucose-6-phosphate, which induces an alternate transport system for FOS, or when grown in the presence of cyclic adenosine 3',5'-monophosphate. A detailed fine-structure map of the pts gene region is presented.", "contents": "Fosfomycin resistance: selection method for internal and extended deletions of the phosphoenolpyruvate:sugar phosphotransferase genes of Salmonella typhimurium. Selection for resistance to the antibiotic fosfomycin (FOS; L-cis 1,2-epoxypropylphosphonic acid, a structural analogue of phosphoenolpyruvate) was used to isolate mutants carrying internal and extended deletions of varying lengths within the ptsHI operon of Salmonella typhimurium. Strains carrying \"tight\" ptsI point mutations and all mutants in which some or all of the ptsI gene was deleted were FOS resistant. In contrast, strains carrying ptsH point mutations were sensitive to FOS. Resistance to FOS appeared to result indirectly from catabolite repression of an FOS transport system, probably the sn-glycerol-3-phosphate transport system. Resistant ptsI mutants became sensitive to FOS when grown on D-glucose-6-phosphate, which induces an alternate transport system for FOS, or when grown in the presence of cyclic adenosine 3',5'-monophosphate. A detailed fine-structure map of the pts gene region is presented."}
{"id": "PMID:186450", "title": "Properties of phenylalanine hydroxylase of cultured hepatoma cells.", "content": "The kinetic and immunologic properties of phenylalanine hydroxylase of adult rat liver were compared to the properties of the similar enzyme present in cultured H4-II-E-C3 hepatoma cells. The enzymes from the two sources could not be distinguished by the Km values for either phenylalanine or 6,7-dimethyltetrahydropterin. Analysis by double immunodiffusion showed that phenylalanine hydroxylase from the two sources had identical immunologic determinants, but immunotitrations revealed a small but significant difference between the enzyme of the normal adult rat liver and the enzyme of cultured hepatoma cells. The results of double immunodiffusion and immunotitration experiments indicated also that the increased levels of phenylalanine hydroxylase seen in the hepatoma cells grown in the presence of hydrocortisone resulted from the accumulation of enzyme protein, but it could not be decided whether this accumulation resulted from an increased rate of synthesis or decreased rate of degradation.", "contents": "Properties of phenylalanine hydroxylase of cultured hepatoma cells. The kinetic and immunologic properties of phenylalanine hydroxylase of adult rat liver were compared to the properties of the similar enzyme present in cultured H4-II-E-C3 hepatoma cells. The enzymes from the two sources could not be distinguished by the Km values for either phenylalanine or 6,7-dimethyltetrahydropterin. Analysis by double immunodiffusion showed that phenylalanine hydroxylase from the two sources had identical immunologic determinants, but immunotitrations revealed a small but significant difference between the enzyme of the normal adult rat liver and the enzyme of cultured hepatoma cells. The results of double immunodiffusion and immunotitration experiments indicated also that the increased levels of phenylalanine hydroxylase seen in the hepatoma cells grown in the presence of hydrocortisone resulted from the accumulation of enzyme protein, but it could not be decided whether this accumulation resulted from an increased rate of synthesis or decreased rate of degradation."}
{"id": "PMID:186451", "title": "31P NMR studies of the arginine kinase reaction. Equilibrium constants and exchange rates at stoichiometric enzyme concentration.", "content": "The arginine kinase reaction, the reversible transfer of the terminal phosphoryl group of ATP to L-arginine, has been investigated by the technique of 31P NMR at catalytic and stoichiometric concentrations of the enzyme. Three of the four substrates, ATP, ADP, and P-arginine produce easily distinguishable resonances in the 31P NMR spectrum, thus permitting a determination of equilibrium constants from the integrated areas of the resonances. From the linewidths, the exchange rates between reactants and products may be evaluated. At pH 7.25 and a temperature of 12 degrees, the equilibrium constant at catalytic enzyme concentration: Keq = [MgADP] [P-arginine]/[MgATP] [L-arginine], is found to be 0.10 +/- 0.02 and that at stoichiometric enzyme concentration: K'eq = [E-MgADP] [E-P-arginine]/[E-MgATP] [E-arginine] to be 1.56 +/- 0.5. Thus, as the enzyme concentration increased, the production of P-arginine is increasingly favored. From the NMR line shapes in the presence of excess enzyme, the rate of the single step, the transfer of the phosphoryl group on the surface of the enzyme is found to be 192 +/- 15 s-1 in the forward direction, i.e. from E-MgATP, and 154 +/- 15 s-1 in the reverse direction from E-P-argine. At 12 degrees and pH 7.25, the rate of the overall reaction in the forward direction was determined from kinetic measurements to be 19 s-1, an order of magnitude slower than the rate measured by NMR. It can, therefore, be concluded that the interconversion of substrates on the surface of the enzyme is not the rate-determining step in the overal reaction. From the equilibrium constants and other known data the dissociation constant of P-arginine from its enzyme complex can be determined and is found to be 100 muM.", "contents": "31P NMR studies of the arginine kinase reaction. Equilibrium constants and exchange rates at stoichiometric enzyme concentration. The arginine kinase reaction, the reversible transfer of the terminal phosphoryl group of ATP to L-arginine, has been investigated by the technique of 31P NMR at catalytic and stoichiometric concentrations of the enzyme. Three of the four substrates, ATP, ADP, and P-arginine produce easily distinguishable resonances in the 31P NMR spectrum, thus permitting a determination of equilibrium constants from the integrated areas of the resonances. From the linewidths, the exchange rates between reactants and products may be evaluated. At pH 7.25 and a temperature of 12 degrees, the equilibrium constant at catalytic enzyme concentration: Keq = [MgADP] [P-arginine]/[MgATP] [L-arginine], is found to be 0.10 +/- 0.02 and that at stoichiometric enzyme concentration: K'eq = [E-MgADP] [E-P-arginine]/[E-MgATP] [E-arginine] to be 1.56 +/- 0.5. Thus, as the enzyme concentration increased, the production of P-arginine is increasingly favored. From the NMR line shapes in the presence of excess enzyme, the rate of the single step, the transfer of the phosphoryl group on the surface of the enzyme is found to be 192 +/- 15 s-1 in the forward direction, i.e. from E-MgATP, and 154 +/- 15 s-1 in the reverse direction from E-P-argine. At 12 degrees and pH 7.25, the rate of the overall reaction in the forward direction was determined from kinetic measurements to be 19 s-1, an order of magnitude slower than the rate measured by NMR. It can, therefore, be concluded that the interconversion of substrates on the surface of the enzyme is not the rate-determining step in the overal reaction. From the equilibrium constants and other known data the dissociation constant of P-arginine from its enzyme complex can be determined and is found to be 100 muM."}
{"id": "PMID:186452", "title": "Reconstitution of biological molecular generators of electric current. Cytochrome oxidase.", "content": "1. Direct measurement of the electric current generation by cytochrome oxidase has been carried out. To this end, two procedures were used. The simpler one consists in formation of planar artificial membrane from the mixture of decane solution of soya bean phospholipids and beef heart cytochrome oxidase. Addition of cytochrome c and ascorbate to one of the two compartments separated by the cytochrome oxidase-containing planar membrane was found to result in a transmembrane electric potential difference being formed (plus on cytochrome c side of the membrane). Maximal values of potential differences obtained by this method were about 40 mV. Much higher potentials were observed when another (\"photeoliposome-planar membrane\") method was applied. In this case cytochrome oxidase was reconstituted with phospholipid to form proteoliposomes which adhered to planar phospholipid membrane in the presence of Ca2+ ions. Addition of cytochrome c and ascorbate to the proteoliposome-containing compartment gives rise to generation of an electric potential difference across the planar membrane, which reached 100 mV at a current of about 1 X 10(-11) A (minus in the proteoliposome-free compartment). The electromotive force of this generator was estimated as being about 0.2 V. If ascorbate and proteoliposomes were added into different compartments, a penetrating hydrogen atom carrier (phenazine methosulfate, (PMS) or tetramethyl-p-phenylenediamine (TMPD)) was required for a membrane potential to be formed. Generation of an electric potential difference of the opposite direction (plus in the proteoliposome-free compartment) was revealed in experiments with cytochrome oxidase proteoliposome containing cytochrome c in their interior. In this case, addition of PMS or TMPD was necessary. 2. In the suspension of cytochrome oxidase proteoliposome the uptake of a cationic penetrant (tetraphenyl phosphonium cation) was found to be coupled with electron transfer via external cytochrome c. Electron transfer via intraproteoliposomal cytochrome c induced the uptake of anionic penetrants (tetraphenyl borate and phenyldicarbaundecaborane anions). 3. All the above effects were sensitive to cyanide and protonophorous uncouplers. 4. In proteoliposomes containing both cytochrome oxidase and bacteriorhodopsin, the light- and oxidation-dependent generations of membrane potential have been revealed. 5. The data obtained are in agreement with Mitchell's idea of transmembrane electron flow in the cytochrome oxidase segment of the respiratory chain.", "contents": "Reconstitution of biological molecular generators of electric current. Cytochrome oxidase. 1. Direct measurement of the electric current generation by cytochrome oxidase has been carried out. To this end, two procedures were used. The simpler one consists in formation of planar artificial membrane from the mixture of decane solution of soya bean phospholipids and beef heart cytochrome oxidase. Addition of cytochrome c and ascorbate to one of the two compartments separated by the cytochrome oxidase-containing planar membrane was found to result in a transmembrane electric potential difference being formed (plus on cytochrome c side of the membrane). Maximal values of potential differences obtained by this method were about 40 mV. Much higher potentials were observed when another (\"photeoliposome-planar membrane\") method was applied. In this case cytochrome oxidase was reconstituted with phospholipid to form proteoliposomes which adhered to planar phospholipid membrane in the presence of Ca2+ ions. Addition of cytochrome c and ascorbate to the proteoliposome-containing compartment gives rise to generation of an electric potential difference across the planar membrane, which reached 100 mV at a current of about 1 X 10(-11) A (minus in the proteoliposome-free compartment). The electromotive force of this generator was estimated as being about 0.2 V. If ascorbate and proteoliposomes were added into different compartments, a penetrating hydrogen atom carrier (phenazine methosulfate, (PMS) or tetramethyl-p-phenylenediamine (TMPD)) was required for a membrane potential to be formed. Generation of an electric potential difference of the opposite direction (plus in the proteoliposome-free compartment) was revealed in experiments with cytochrome oxidase proteoliposome containing cytochrome c in their interior. In this case, addition of PMS or TMPD was necessary. 2. In the suspension of cytochrome oxidase proteoliposome the uptake of a cationic penetrant (tetraphenyl phosphonium cation) was found to be coupled with electron transfer via external cytochrome c. Electron transfer via intraproteoliposomal cytochrome c induced the uptake of anionic penetrants (tetraphenyl borate and phenyldicarbaundecaborane anions). 3. All the above effects were sensitive to cyanide and protonophorous uncouplers. 4. In proteoliposomes containing both cytochrome oxidase and bacteriorhodopsin, the light- and oxidation-dependent generations of membrane potential have been revealed. 5. The data obtained are in agreement with Mitchell's idea of transmembrane electron flow in the cytochrome oxidase segment of the respiratory chain."}
{"id": "PMID:186453", "title": "Purification and characterization of an endoribonuclease from nucleoplasm and nucleoli of HeLa cells.", "content": "An endoribonuclease has been isolated from HeLa cell nuclei. Approximately 70% of the enzyme appears to be nucleolar bound; 30% is in the nucleoplasm. Studies of the purified enzyme reveal that the enzyme is an endonuclease of estimated molecular weight 16,000. It produces oligonucleotides bearing 5'-phosphate end groups. The enzyme degrades poly(C) and poly(U), as well as rRNA and heterogeneous nuclear RNA, Poly(A), double-stranded RNA, and DNA are not cleaved. The enzyme is heat-labile and is inhibited by 10mM Mg2+ and 50 mM NaCl. The enzyme is probably distinct from previously described nuclear endonucleases.", "contents": "Purification and characterization of an endoribonuclease from nucleoplasm and nucleoli of HeLa cells. An endoribonuclease has been isolated from HeLa cell nuclei. Approximately 70% of the enzyme appears to be nucleolar bound; 30% is in the nucleoplasm. Studies of the purified enzyme reveal that the enzyme is an endonuclease of estimated molecular weight 16,000. It produces oligonucleotides bearing 5'-phosphate end groups. The enzyme degrades poly(C) and poly(U), as well as rRNA and heterogeneous nuclear RNA, Poly(A), double-stranded RNA, and DNA are not cleaved. The enzyme is heat-labile and is inhibited by 10mM Mg2+ and 50 mM NaCl. The enzyme is probably distinct from previously described nuclear endonucleases."}
{"id": "PMID:186454", "title": "Intracellular location of triple helix formation of collagen. Enzyme probe studies.", "content": "Primary cultures of chick embryo fibroblasts were used to study ribosomal events in the processing of procollagen. Polyribosomes from radiolabeled cells were subjected to enzyme probe analysis using collagenase and pepsin digestion to assess both the amount of procollagen present on the polyribosomes and the conformation of the molecule. The peptides rendered dialyzable by each enzyme treatment were analyzed for radioactive proline and hydroxyproline. Approximately 30% of the nascent proteins were collagenous. Although some hydroxyproline was dialyzable in the pepsin-treated material, a low ratio of hydroxyproline to proline (0.04) indicated that considerable amounts of noncollagenous proteins were digested. Polyribosomal material, previously treated with pepsin, was digested with purified collagenase. Similarly, collagenase-digested polyribosomes were treated with pepsin. The pepsin pretreatment released noncollagenous protein and served to purify the remaining ribosomally bound pepsin-resistant collagenous protein. Collagenase treatment of the pepsin-resistant ribosomally bound peptides released peptides with a hydroxyproline to proline ratio of 0.65, indicating that considerable hydroxylation of proline occurs on nascent ribosomally bound procollagen. This finding combined with the well documented stabilizing effect of hydroxyproline on the collagen triple helix and the demonstrated resistance of ribosomally bound procollagen to pepsin digestion indicates that the collagen triple helix may well form on the polyribosome.", "contents": "Intracellular location of triple helix formation of collagen. Enzyme probe studies. Primary cultures of chick embryo fibroblasts were used to study ribosomal events in the processing of procollagen. Polyribosomes from radiolabeled cells were subjected to enzyme probe analysis using collagenase and pepsin digestion to assess both the amount of procollagen present on the polyribosomes and the conformation of the molecule. The peptides rendered dialyzable by each enzyme treatment were analyzed for radioactive proline and hydroxyproline. Approximately 30% of the nascent proteins were collagenous. Although some hydroxyproline was dialyzable in the pepsin-treated material, a low ratio of hydroxyproline to proline (0.04) indicated that considerable amounts of noncollagenous proteins were digested. Polyribosomal material, previously treated with pepsin, was digested with purified collagenase. Similarly, collagenase-digested polyribosomes were treated with pepsin. The pepsin pretreatment released noncollagenous protein and served to purify the remaining ribosomally bound pepsin-resistant collagenous protein. Collagenase treatment of the pepsin-resistant ribosomally bound peptides released peptides with a hydroxyproline to proline ratio of 0.65, indicating that considerable hydroxylation of proline occurs on nascent ribosomally bound procollagen. This finding combined with the well documented stabilizing effect of hydroxyproline on the collagen triple helix and the demonstrated resistance of ribosomally bound procollagen to pepsin digestion indicates that the collagen triple helix may well form on the polyribosome."}
{"id": "PMID:186455", "title": "Evidence for participation of iron in lipoxygenase reaction from optical and electron spin resonance studies.", "content": "Optical and EPR studies indicate that the iron present in lipoxygenase participates in catalysis. Addition of linoleic acid hydroperoxide to lipoxygenase 1 causes an increase in abosrbance over the range of 350 to 650 nm which is reversed when linoleic acid hydroperoxide is destroyed upon the addition of linoleic acid under anaerobic conditions. Lipoxygenase 1 alone exhibits no EPR signal but upon addition of linoleic acid hydroperoxide or linoleic acid several signals appear. Addition of linoleic acid hydroperoxide results in an EPR signal at g approximately equal to 6 accompanied by a small but relatively sharp signal at g approximately equal to 2. Under anaerobic conditions the latter is replaced by a broad anisotropic signal around g approximately equal to 2. The appearance of the EPR signal at g approximately equal to 6 coincides with the change in the optical spectrum of the enzyme. When linoleic acid is added under anaerobic conditions a broad anisotropic EPR signal around g approximately equal to 2 is observed. Thus it appears that lipoxygenase can exist in two forms: (a) a resting form with a very weak absorbance in the visible range of the light spectrum and no EPR signal and (b) an active form (after addition of linoleic acid hydroperoxide) with an increased optical absorbance and EPR signal at g approximately equal to 6. This observation may be related to the earlier discovery that the lipoxygenase reaction occurs with a lag which can be overcome by addition of product hydroperoxide. The EPR experiments indicate that lipoxygenase in the active form contains high spin ferric ion. Although EPR signals in the g approximately equal to 6 region are frequently observed with heme proteins, the only nonheme protein, other than lipoxygenase, reported to show an EPR signal in this region is the phenolytic dioxygenase, protocatechuate 3,4-dioxygenase (Peisach, J., Fujisawa, H., Blumberg, W. E., and Hayaishi, O. (1972) Fed. Proc. 31, 448).", "contents": "Evidence for participation of iron in lipoxygenase reaction from optical and electron spin resonance studies. Optical and EPR studies indicate that the iron present in lipoxygenase participates in catalysis. Addition of linoleic acid hydroperoxide to lipoxygenase 1 causes an increase in abosrbance over the range of 350 to 650 nm which is reversed when linoleic acid hydroperoxide is destroyed upon the addition of linoleic acid under anaerobic conditions. Lipoxygenase 1 alone exhibits no EPR signal but upon addition of linoleic acid hydroperoxide or linoleic acid several signals appear. Addition of linoleic acid hydroperoxide results in an EPR signal at g approximately equal to 6 accompanied by a small but relatively sharp signal at g approximately equal to 2. Under anaerobic conditions the latter is replaced by a broad anisotropic signal around g approximately equal to 2. The appearance of the EPR signal at g approximately equal to 6 coincides with the change in the optical spectrum of the enzyme. When linoleic acid is added under anaerobic conditions a broad anisotropic EPR signal around g approximately equal to 2 is observed. Thus it appears that lipoxygenase can exist in two forms: (a) a resting form with a very weak absorbance in the visible range of the light spectrum and no EPR signal and (b) an active form (after addition of linoleic acid hydroperoxide) with an increased optical absorbance and EPR signal at g approximately equal to 6. This observation may be related to the earlier discovery that the lipoxygenase reaction occurs with a lag which can be overcome by addition of product hydroperoxide. The EPR experiments indicate that lipoxygenase in the active form contains high spin ferric ion. Although EPR signals in the g approximately equal to 6 region are frequently observed with heme proteins, the only nonheme protein, other than lipoxygenase, reported to show an EPR signal in this region is the phenolytic dioxygenase, protocatechuate 3,4-dioxygenase (Peisach, J., Fujisawa, H., Blumberg, W. E., and Hayaishi, O. (1972) Fed. Proc. 31, 448)."}
{"id": "PMID:186456", "title": "Equilibrium constants under physiological conditions for the reactions of choline kinase and the hydrolysis of phosphorylcholine to choline and inorganic phosphate.", "content": "The observed equilibrium constants (Kobs) of the P-choline hydrolysis reaction have been determined under physiological conditions of temperature (38 degrees) and ionic strength (0.25 M) and physiological ranges of pH and free [Mg2+]. Using sigma and square brackets to indicate total concentrations: (see article.) The value of Kobs has been found to be relatively insensitive to variations in pH and free [Mg2+]. At pH 7.0 and taking the standard state of liquid water to have unit activity ([H2O] = 1), Kobs = 26.6 M at free [Mg2+] = 0 [epsilon G0obs = -2.03 kcal/mol(-8.48 kJ/mol)], 26.8 M at free [Mg2+] = 10(-3) M, and 28.4 M at free [Mg2+] = 10(-2) M. At pH 8.0, Kobs = 18.8 M at free [Mg2+] = 0, 19.2 M at free [Mg2+] = 10(-3), and 22.2 M at free [Mg2+] = 10(-2) M. These values apply only to situations where choline and Pi concentrations are both relatively low (such as the conditions found in most tissues). At higher concentrations of phosphate and choline, the value of Kobs becomes significantly increased since HPO42- complexes choline weakly (association constant = 3.3 M-1). The value of K at 38 degrees and I = 0.25 M is calculated to be 16.4 +/- 0.3 M [epsilonG0 = 1.73 kcal/mol (-7.23 kJ/mol)]. The K for the P-choline hydrolysis reaction has been combined with the K for the ATP hydrolysis reaction determined previously under physiological conditions to calculate a value of 4.95 X 10(-3 M [deltaG0 j.28 kcal/mol (13.7 kJ/mol] for the K of the choline kinase reaction (EC 2.7.1.32), an important step in phospholipid metabolism: (see article.) Likewise, values for Kobs for the choline kinase reaction at 38 degrees, pH 7.0, and I = 0.25 M have been calculated to be 5.76 X 10(4) [deltaG0OBS = -6.77 KCAL/MOL (-28.3 KJ/mol)] at [Mg2+] = 0; 1.24 X  10(4) [deltaG0obs = -5.82 kcal/mol (-24.4 kJ/mol)] at [Mg2+] = 10(-3) M and 8.05 X 10(3) [delta G0obs = -5.56 kcal/mol (-23.3 kJ/mol)] at [Mg2+ = 10(-2) M. Attempts to determine the Kobs of the choline kinase reaction directly were unsuccessful because of the high value of the constant. The results indicate that in contrast to the high deltaG0obs for the hydrolysis of the ester bond of acetylcholine, the deltaG0obs for the hydrolysis of the ester bond of P-choline is quite low, among the lowest known for phosphate ester bonds of biological interest.", "contents": "Equilibrium constants under physiological conditions for the reactions of choline kinase and the hydrolysis of phosphorylcholine to choline and inorganic phosphate. The observed equilibrium constants (Kobs) of the P-choline hydrolysis reaction have been determined under physiological conditions of temperature (38 degrees) and ionic strength (0.25 M) and physiological ranges of pH and free [Mg2+]. Using sigma and square brackets to indicate total concentrations: (see article.) The value of Kobs has been found to be relatively insensitive to variations in pH and free [Mg2+]. At pH 7.0 and taking the standard state of liquid water to have unit activity ([H2O] = 1), Kobs = 26.6 M at free [Mg2+] = 0 [epsilon G0obs = -2.03 kcal/mol(-8.48 kJ/mol)], 26.8 M at free [Mg2+] = 10(-3) M, and 28.4 M at free [Mg2+] = 10(-2) M. At pH 8.0, Kobs = 18.8 M at free [Mg2+] = 0, 19.2 M at free [Mg2+] = 10(-3), and 22.2 M at free [Mg2+] = 10(-2) M. These values apply only to situations where choline and Pi concentrations are both relatively low (such as the conditions found in most tissues). At higher concentrations of phosphate and choline, the value of Kobs becomes significantly increased since HPO42- complexes choline weakly (association constant = 3.3 M-1). The value of K at 38 degrees and I = 0.25 M is calculated to be 16.4 +/- 0.3 M [epsilonG0 = 1.73 kcal/mol (-7.23 kJ/mol)]. The K for the P-choline hydrolysis reaction has been combined with the K for the ATP hydrolysis reaction determined previously under physiological conditions to calculate a value of 4.95 X 10(-3 M [deltaG0 j.28 kcal/mol (13.7 kJ/mol] for the K of the choline kinase reaction (EC 2.7.1.32), an important step in phospholipid metabolism: (see article.) Likewise, values for Kobs for the choline kinase reaction at 38 degrees, pH 7.0, and I = 0.25 M have been calculated to be 5.76 X 10(4) [deltaG0OBS = -6.77 KCAL/MOL (-28.3 KJ/mol)] at [Mg2+] = 0; 1.24 X  10(4) [deltaG0obs = -5.82 kcal/mol (-24.4 kJ/mol)] at [Mg2+] = 10(-3) M and 8.05 X 10(3) [delta G0obs = -5.56 kcal/mol (-23.3 kJ/mol)] at [Mg2+ = 10(-2) M. Attempts to determine the Kobs of the choline kinase reaction directly were unsuccessful because of the high value of the constant. The results indicate that in contrast to the high deltaG0obs for the hydrolysis of the ester bond of acetylcholine, the deltaG0obs for the hydrolysis of the ester bond of P-choline is quite low, among the lowest known for phosphate ester bonds of biological interest."}
{"id": "PMID:186457", "title": "In vivo tissue reactivity of radiation-cured silicone rubber implants.", "content": "Silicone rubber implants are clinically used in large numbers and elicit a milk tissue reaction. An occasional patient develops an accentuated reaction, an observation which has stimulated clinicians to try to understand this process more fully. The chemistry of medical silicone implants, including quantitative composition, is reviewed. This in vitro laboratory study show less tissue reaction-cured silicone with SiO2 filler. A proposed system for fabrication and curing of a silicone implant, with the qualities of strength and diminished tissue reactivity, is discussed.", "contents": "In vivo tissue reactivity of radiation-cured silicone rubber implants. Silicone rubber implants are clinically used in large numbers and elicit a milk tissue reaction. An occasional patient develops an accentuated reaction, an observation which has stimulated clinicians to try to understand this process more fully. The chemistry of medical silicone implants, including quantitative composition, is reviewed. This in vitro laboratory study show less tissue reaction-cured silicone with SiO2 filler. A proposed system for fabrication and curing of a silicone implant, with the qualities of strength and diminished tissue reactivity, is discussed."}
{"id": "PMID:186458", "title": "Biomaterials and collagen synthesis.", "content": "A highly reactive biomaterial (clay) and a relatively nonreactive substance (silicone) were implanted separately in primarily closed incisions on the backs of rats. Collagen synthesis was determined in biopsies from each test site after 8 days. The biochemical measurements of collagen synthesis showed a significant correlation with the gross pathologic and histologic findings.", "contents": "Biomaterials and collagen synthesis. A highly reactive biomaterial (clay) and a relatively nonreactive substance (silicone) were implanted separately in primarily closed incisions on the backs of rats. Collagen synthesis was determined in biopsies from each test site after 8 days. The biochemical measurements of collagen synthesis showed a significant correlation with the gross pathologic and histologic findings."}
{"id": "PMID:186459", "title": "Recent experience in mammography using Trimax rare-earth system.", "content": "Comparison of two substantial series of mammograms has shown that reduction in exposure time from about five seconds to about two seconds, all other factors remaining equal, has made no difference in the true positive rate of diagnostic accuracy. However, the amount of radiation to the breast was reduced. Using rare-earth screen and film combinations allows a further dramatic reduction in the exposure time as well as in the kilovoltage and milli-amperage without any apparent loss in quality. Since the amount of radiation is one important factor, serious consideration must be given to the use of rare-earth screen and film combination for mammography.", "contents": "Recent experience in mammography using Trimax rare-earth system. Comparison of two substantial series of mammograms has shown that reduction in exposure time from about five seconds to about two seconds, all other factors remaining equal, has made no difference in the true positive rate of diagnostic accuracy. However, the amount of radiation to the breast was reduced. Using rare-earth screen and film combinations allows a further dramatic reduction in the exposure time as well as in the kilovoltage and milli-amperage without any apparent loss in quality. Since the amount of radiation is one important factor, serious consideration must be given to the use of rare-earth screen and film combination for mammography."}
{"id": "PMID:186461", "title": "Adenosine 3':5'-monophosphate content and actions in the division cycle of synchronized HeLa cells.", "content": "The involvement of adenosine 3':5'-monophosphate (cAMP) in the regulation of the cell cycle was studied by determining intracellular fluctuations in cAMP levels in synchronized HeLa cells and by testing the effects of experimentally altered levels on cell cycle traverse. Cyclic AMP levels were lowest during mitosis and were highest during late G-1 or early S phase. These findings were supported by results obtained when cells were accumulated at these points with Colcemid or high levels of thymidine. Additional fluctuations in cAMP levels were observed during S phase. Two specific effects of cAMP on cell cycle traverse were found. Elevation of cAMP levels in S phase or G-2 caused arrest of cells in G-2 for as long as 10 h and lengthened M. However, once cells reached metaphase, elevation of cAMP accelerated the completion of mitosis. Stimulation of mitosis was also observed after addition of CaCl2. The specificity of the effects of cAMP was verified by demonstrating that: (a) intracellular cAMP was increased after exposure to methylisobutylxanthine (MIX) before any observed effects on cycle traverse; (b) submaximal concentrations of MIX potentiated the effects of isoproterenol; and (c) effects of MIX and isoproterenol were mimicked by 8-Br-cAMP. MIX at high concentrations inhibited G-1 traverse, but this effect did not appear to be mediated by cAMP. Isoproterenol slightly stimulated G-1 traverse and partially prevented the MIX-induced delay. Moreover, low concentrations of 8-Br-cAMP (0.10-100 muM) stimulated G-1 traverse, whereas high concentrations (1 mM) inhibited. Both of these effects were also observed with the control, Br-5'-AMP, at 10-fold lower concentrations.", "contents": "Adenosine 3':5'-monophosphate content and actions in the division cycle of synchronized HeLa cells. The involvement of adenosine 3':5'-monophosphate (cAMP) in the regulation of the cell cycle was studied by determining intracellular fluctuations in cAMP levels in synchronized HeLa cells and by testing the effects of experimentally altered levels on cell cycle traverse. Cyclic AMP levels were lowest during mitosis and were highest during late G-1 or early S phase. These findings were supported by results obtained when cells were accumulated at these points with Colcemid or high levels of thymidine. Additional fluctuations in cAMP levels were observed during S phase. Two specific effects of cAMP on cell cycle traverse were found. Elevation of cAMP levels in S phase or G-2 caused arrest of cells in G-2 for as long as 10 h and lengthened M. However, once cells reached metaphase, elevation of cAMP accelerated the completion of mitosis. Stimulation of mitosis was also observed after addition of CaCl2. The specificity of the effects of cAMP was verified by demonstrating that: (a) intracellular cAMP was increased after exposure to methylisobutylxanthine (MIX) before any observed effects on cycle traverse; (b) submaximal concentrations of MIX potentiated the effects of isoproterenol; and (c) effects of MIX and isoproterenol were mimicked by 8-Br-cAMP. MIX at high concentrations inhibited G-1 traverse, but this effect did not appear to be mediated by cAMP. Isoproterenol slightly stimulated G-1 traverse and partially prevented the MIX-induced delay. Moreover, low concentrations of 8-Br-cAMP (0.10-100 muM) stimulated G-1 traverse, whereas high concentrations (1 mM) inhibited. Both of these effects were also observed with the control, Br-5'-AMP, at 10-fold lower concentrations."}
{"id": "PMID:186462", "title": "Microtubule assembly in cultivated Greene melanoma cells is stimulated by dibutyryl adenosine 3':5'-cyclic monophosphate or cholera toxin.", "content": "Both dibutyryl cyclic AMP (DBcAMP) and cholera toxin promote the formation and elongation of processes of cultivated Greene hamster melanoma cells. The formation and maintenance of these processes, which contain many microtubules, are sensitive to colcemid and vinblastine. Tubulin was measured by [3H]colchicine binding and by acrylamide gel electrophoresis. We found that DBcAMP or cholera toxin increases the ratio of polymerized to unpolymerized tubulin but not the total amount of tubulin per cell. The sum of the lengths of microtubules per unit area was significantly greater in cells treated with DBcAMP than in control cells. Our findings support the hypothesis that cyclic AMP promotes the elongation of cell processes by stimulating the assembly of microtubules from existing tubulin.", "contents": "Microtubule assembly in cultivated Greene melanoma cells is stimulated by dibutyryl adenosine 3':5'-cyclic monophosphate or cholera toxin. Both dibutyryl cyclic AMP (DBcAMP) and cholera toxin promote the formation and elongation of processes of cultivated Greene hamster melanoma cells. The formation and maintenance of these processes, which contain many microtubules, are sensitive to colcemid and vinblastine. Tubulin was measured by [3H]colchicine binding and by acrylamide gel electrophoresis. We found that DBcAMP or cholera toxin increases the ratio of polymerized to unpolymerized tubulin but not the total amount of tubulin per cell. The sum of the lengths of microtubules per unit area was significantly greater in cells treated with DBcAMP than in control cells. Our findings support the hypothesis that cyclic AMP promotes the elongation of cell processes by stimulating the assembly of microtubules from existing tubulin."}
{"id": "PMID:186463", "title": "Specific changes in the synthesis of mitochondrial DNA in chick embryo fibroblasts transformed by Rous sarcoma viruses.", "content": "In chick-embryo fibroblasts infected with the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup A (wild type), or with a thermosensitive mutant of this virus, T5, the rates of mitochondrial DNA synthesis differ in cells that exhibit normal and malignant phenotypes. In wild type virus-infected cells grown at 36 or 41 degrees C, morphological transformation is expressed, the rate of 2-deoxy-D-[3H]glucose uptake is stimulated, and mitochondrial DNA synthesis in vivo is stimulated three- to fivefold over that in uninfected cells. In T5-infected cells these changes occur only at the permissive temperature (36 degrees C); a shift to the nonpermissive temperature (41 degrees C) causes the reversal of these effects, and the specific activity of purified mitochondrial DNA is characteristic of that from uninfected cells. In contrast, the specific activities of nuclear DNA purified from cells maximally transformed under the permissive conditions do not differ between wild type-infected and uninfected with the T5 virus. In parallel experiments with isolated mitochondria, the rate of mtDNA synthesis in vitro is again greater in mitochondria isolated from transformed cells. In addition, mitochondrial DNA synthesis in vitro in mitochondria from nontransformed and virus-transformed cells exhibits differential sensitivity to inhibition by mercaptoethanol. Furthermore, the ntDNAP polymerase activity in mitochondrial extracts prepared from cells with transformed phenotypes is about sevenfold higher than in extracts from cells with nontransformed phenotypes.", "contents": "Specific changes in the synthesis of mitochondrial DNA in chick embryo fibroblasts transformed by Rous sarcoma viruses. In chick-embryo fibroblasts infected with the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup A (wild type), or with a thermosensitive mutant of this virus, T5, the rates of mitochondrial DNA synthesis differ in cells that exhibit normal and malignant phenotypes. In wild type virus-infected cells grown at 36 or 41 degrees C, morphological transformation is expressed, the rate of 2-deoxy-D-[3H]glucose uptake is stimulated, and mitochondrial DNA synthesis in vivo is stimulated three- to fivefold over that in uninfected cells. In T5-infected cells these changes occur only at the permissive temperature (36 degrees C); a shift to the nonpermissive temperature (41 degrees C) causes the reversal of these effects, and the specific activity of purified mitochondrial DNA is characteristic of that from uninfected cells. In contrast, the specific activities of nuclear DNA purified from cells maximally transformed under the permissive conditions do not differ between wild type-infected and uninfected with the T5 virus. In parallel experiments with isolated mitochondria, the rate of mtDNA synthesis in vitro is again greater in mitochondria isolated from transformed cells. In addition, mitochondrial DNA synthesis in vitro in mitochondria from nontransformed and virus-transformed cells exhibits differential sensitivity to inhibition by mercaptoethanol. Furthermore, the ntDNAP polymerase activity in mitochondrial extracts prepared from cells with transformed phenotypes is about sevenfold higher than in extracts from cells with nontransformed phenotypes."}
{"id": "PMID:186464", "title": "Isolation of synaptic junctional complexes of high structural integrity from rat brain.", "content": "A new method has been developed for isolating synaptic junctional complexes (SJC) of high structural integrity. The major step in the isolation involves homogenization of a synaptosomal membrane (SM) fraction in a biphasic system consisting of Freon 113 and an aqueous phase containing 0.2% Triton X-100. Well-preserved SJCs, along with membrane vesicles, were recovered in the aqueous phase after low-speed centrifugation of the homogenate. The membranes were subsequently separated from the SJCs by centrifugation on a discontinuous sucrose density gradient. The purity and identity of subcellular fractions were monitored by thin sectioning electron microscopy, using specific and nonspecific staining methods. From the electron microscope studies we conclude that SJCs and their components occupy about 65% of the area covered by structures in this fraction. The assay of enzyme activities indicates that homogenization in Triton-Freon and subsequent steps of the isolation procedure affect the activities of Na, K-ATPase, cytochrome oxidase, and acid phosphatase to different extents, but do not cause total inactivation. Electrophoresis of the SJC-enriched fraction on sodium dodecyl sulfate-polyacrylamide gels has demonstrated that a polypeptide which co-migrates with tubulin is the major component in this fraction, and that a polypeptide co-migrating with actin is also present.", "contents": "Isolation of synaptic junctional complexes of high structural integrity from rat brain. A new method has been developed for isolating synaptic junctional complexes (SJC) of high structural integrity. The major step in the isolation involves homogenization of a synaptosomal membrane (SM) fraction in a biphasic system consisting of Freon 113 and an aqueous phase containing 0.2% Triton X-100. Well-preserved SJCs, along with membrane vesicles, were recovered in the aqueous phase after low-speed centrifugation of the homogenate. The membranes were subsequently separated from the SJCs by centrifugation on a discontinuous sucrose density gradient. The purity and identity of subcellular fractions were monitored by thin sectioning electron microscopy, using specific and nonspecific staining methods. From the electron microscope studies we conclude that SJCs and their components occupy about 65% of the area covered by structures in this fraction. The assay of enzyme activities indicates that homogenization in Triton-Freon and subsequent steps of the isolation procedure affect the activities of Na, K-ATPase, cytochrome oxidase, and acid phosphatase to different extents, but do not cause total inactivation. Electrophoresis of the SJC-enriched fraction on sodium dodecyl sulfate-polyacrylamide gels has demonstrated that a polypeptide which co-migrates with tubulin is the major component in this fraction, and that a polypeptide co-migrating with actin is also present."}
{"id": "PMID:186465", "title": "Effects of 5-bromodeoxyuridine on the ACTH-dependent mitochondrial biogenesis in cortical cells of fetal rat adrenals in tissue culture.", "content": "Cortical cells of fetal rat adrenals in tissue culture were treated with 5-bromodeoxyuridine (BrdU) during their proliferative phase and during ACTH stimulation when nuclear DNA synthesis has almost ceased. Pretreatment with 0.5 mug/ml/day of BrdU inhibited the ACTH-induced differentiation of cortical cells as well as the secretion of corticosterone and 18-OH-deoxycorticosterone (18-OHDOC). When nuclear DNA synthesis was suppressed and mitochondrial DNA synthesis was stimulated by ACTH BrdU addition (30 mug/ml/day) permitted normal untrastructural differentiation of cortical cells, except that the development of mitochondrial inner membranes was inhibited. Simultaneously mitochondrial inner membranes was inhibited. Simultaneously mitochondrial 11beta- and 18-hydroxylations were strongly inhibited while cytoplasmic 21-hydroxylation was not affected.", "contents": "Effects of 5-bromodeoxyuridine on the ACTH-dependent mitochondrial biogenesis in cortical cells of fetal rat adrenals in tissue culture. Cortical cells of fetal rat adrenals in tissue culture were treated with 5-bromodeoxyuridine (BrdU) during their proliferative phase and during ACTH stimulation when nuclear DNA synthesis has almost ceased. Pretreatment with 0.5 mug/ml/day of BrdU inhibited the ACTH-induced differentiation of cortical cells as well as the secretion of corticosterone and 18-OH-deoxycorticosterone (18-OHDOC). When nuclear DNA synthesis was suppressed and mitochondrial DNA synthesis was stimulated by ACTH BrdU addition (30 mug/ml/day) permitted normal untrastructural differentiation of cortical cells, except that the development of mitochondrial inner membranes was inhibited. Simultaneously mitochondrial inner membranes was inhibited. Simultaneously mitochondrial 11beta- and 18-hydroxylations were strongly inhibited while cytoplasmic 21-hydroxylation was not affected."}
{"id": "PMID:186469", "title": "Densitometric quantitation of neutral lipids on ammonium sulfate impregnated thin-layer chromatograms.", "content": "A procedure is described which extends the densitometric quantitation of phospholipids on ammonium sulfate impregnated thin-layer chromatograms by Gluck et al. to include total lipid, free and esterified cholesterol, free fatty acid and triglyceride. Lipids separated on thin-layer plates containing silica gel G impregnated with ammonium sulfate were charred upon heating and absorbance was measured densitometrically. Thus, the necessity of spraying or submersing in a charring agent was eliminated, uniform charring became possible, and quantitation over a wider range of sample sizes than most densitometric procedures was obtained. One linear relationship existed for concentrations of standards over the range of 0.0-3.0 mug and another line from 4.0-50.0 mug. Both accuracy and precision of the method were highly reliable.", "contents": "Densitometric quantitation of neutral lipids on ammonium sulfate impregnated thin-layer chromatograms. A procedure is described which extends the densitometric quantitation of phospholipids on ammonium sulfate impregnated thin-layer chromatograms by Gluck et al. to include total lipid, free and esterified cholesterol, free fatty acid and triglyceride. Lipids separated on thin-layer plates containing silica gel G impregnated with ammonium sulfate were charred upon heating and absorbance was measured densitometrically. Thus, the necessity of spraying or submersing in a charring agent was eliminated, uniform charring became possible, and quantitation over a wider range of sample sizes than most densitometric procedures was obtained. One linear relationship existed for concentrations of standards over the range of 0.0-3.0 mug and another line from 4.0-50.0 mug. Both accuracy and precision of the method were highly reliable."}
{"id": "PMID:186470", "title": "High-speed liquid and thin-layer chromatography of polychlorinated biphenyls.", "content": "High-speed liquid chromatography in the system silica gel/dry n-hexane and ultraviolet spectrometry have been used to study the composition of various types of commercially available mixtures of chlorinated biphenyls. Special attention has been paid to the analysis of highly chlorinated products. In addition to data previously published, retention times are recorded for 11 individual polychlorinated biphenyls. The results of high-speed liquid chromatography are compared with those obtained in several normal and reversed-phase thin-layer chromatographic systems.", "contents": "High-speed liquid and thin-layer chromatography of polychlorinated biphenyls. High-speed liquid chromatography in the system silica gel/dry n-hexane and ultraviolet spectrometry have been used to study the composition of various types of commercially available mixtures of chlorinated biphenyls. Special attention has been paid to the analysis of highly chlorinated products. In addition to data previously published, retention times are recorded for 11 individual polychlorinated biphenyls. The results of high-speed liquid chromatography are compared with those obtained in several normal and reversed-phase thin-layer chromatographic systems."}
{"id": "PMID:186471", "title": "Quantitative high-performance liquid chromatography of diazepam and N-desmethyldiazepam in blood.", "content": "High-performance liquid chromatography on porous silica has been employed to determine diazepam and N-desmethyldiazepam in human blood. For forensic purposes, 1.0 ml of blood is sufficient for a quantitative determination of the benzodiazepines in concentrations above 100 ng/ml. In cases where lower levels, 25-100 ng/ml, are of interest, 2.0 ml of blood together with a somewhat more elaborate extraction procedure are necessary.", "contents": "Quantitative high-performance liquid chromatography of diazepam and N-desmethyldiazepam in blood. High-performance liquid chromatography on porous silica has been employed to determine diazepam and N-desmethyldiazepam in human blood. For forensic purposes, 1.0 ml of blood is sufficient for a quantitative determination of the benzodiazepines in concentrations above 100 ng/ml. In cases where lower levels, 25-100 ng/ml, are of interest, 2.0 ml of blood together with a somewhat more elaborate extraction procedure are necessary."}
{"id": "PMID:186473", "title": "Impaired glucose, insulin, and adenosine 3',5'-monophosphate responses to glucagon in growth hormone deficient children.", "content": "The glucose, insulin, and adenosine 3',5'-monophosphate (cyclic AMP) responses to intravenous glucagon were found to be impaired in growth hormone deficient children. The delta plasma glucose response in 22 normal children was 54.5 mg/dl compared to 38.4 mg/dl in the 11 growth hormone deficient children; t = 2.74, P less than 0.02. For serum insulin, the comparative values were 65.3 muU/ml (n = 20) vs. 29.8 muU/ml (n = 11); t = 3.03, P less than 0.01. For urinary cyclic AMP, the comparative values were 0.46 mumol/m2 (n = 22) vs. 0.18 mumol/m2 (n = 10); t = 2.48, P less than 0.02. Growth hormone therapy resulted in a significant improvement in the glucose, insulin, and cyclic AMP responses to intravenous glucagon in the growth hormone deficient group of children.", "contents": "Impaired glucose, insulin, and adenosine 3',5'-monophosphate responses to glucagon in growth hormone deficient children. The glucose, insulin, and adenosine 3',5'-monophosphate (cyclic AMP) responses to intravenous glucagon were found to be impaired in growth hormone deficient children. The delta plasma glucose response in 22 normal children was 54.5 mg/dl compared to 38.4 mg/dl in the 11 growth hormone deficient children; t = 2.74, P less than 0.02. For serum insulin, the comparative values were 65.3 muU/ml (n = 20) vs. 29.8 muU/ml (n = 11); t = 3.03, P less than 0.01. For urinary cyclic AMP, the comparative values were 0.46 mumol/m2 (n = 22) vs. 0.18 mumol/m2 (n = 10); t = 2.48, P less than 0.02. Growth hormone therapy resulted in a significant improvement in the glucose, insulin, and cyclic AMP responses to intravenous glucagon in the growth hormone deficient group of children."}
{"id": "PMID:186474", "title": "Somatomedin-C receptor ontogeny and levels in porcine fetal and human cord serum.", "content": "The ontogeny of somatomedin receptors in tissues of fetal pigs and levels of somatomedin-C in fetal pig serum at various gestational ages and in human cord serum was investigated. Specific binding of 125I somatomedin-C by particulate membranes prepared from fetal organs from a variety of gestational ages almost always exceeds specific 125I insulin binding. In liver, kidney, heart and the maternal portion of the placenta, apparent binding affinity for somatomedin is relatively constant throughout gestation and is the same for membranes from fetal and adult animals. In contrast, in the fetal portion of the placenta, specific somatomedin-C binding and apparent binding affinity increases as gestation progresses. The changes in this tissue correlate temporally with the acceleration of growth of the pig fetus. Membranes prepared from fetal lungs exhibit higher specific binding of somatomedin and higher affinity constants than adult lung membranes. Somatomedin levels in fetal pig serum are about 25% of those observed in the sow and are constant throughout fetal life. Somatomedin in human cord serum is likewise low compared to adult levels. Small-for-gestational age infants and large, postmature infants have lower mean somatomedin levels than normal weight, full-term infants. The identification of specific somatomedin receptors in fetal tissues opens the possibility that somatomedin-C stimulates growth of the fetus. Although not resolved, the relatively low levels of somatomedin in fetal serum may reflect low levels of the somatomedin binding protein rather than an absolute deficiency of biologically active somatomedin.", "contents": "Somatomedin-C receptor ontogeny and levels in porcine fetal and human cord serum. The ontogeny of somatomedin receptors in tissues of fetal pigs and levels of somatomedin-C in fetal pig serum at various gestational ages and in human cord serum was investigated. Specific binding of 125I somatomedin-C by particulate membranes prepared from fetal organs from a variety of gestational ages almost always exceeds specific 125I insulin binding. In liver, kidney, heart and the maternal portion of the placenta, apparent binding affinity for somatomedin is relatively constant throughout gestation and is the same for membranes from fetal and adult animals. In contrast, in the fetal portion of the placenta, specific somatomedin-C binding and apparent binding affinity increases as gestation progresses. The changes in this tissue correlate temporally with the acceleration of growth of the pig fetus. Membranes prepared from fetal lungs exhibit higher specific binding of somatomedin and higher affinity constants than adult lung membranes. Somatomedin levels in fetal pig serum are about 25% of those observed in the sow and are constant throughout fetal life. Somatomedin in human cord serum is likewise low compared to adult levels. Small-for-gestational age infants and large, postmature infants have lower mean somatomedin levels than normal weight, full-term infants. The identification of specific somatomedin receptors in fetal tissues opens the possibility that somatomedin-C stimulates growth of the fetus. Although not resolved, the relatively low levels of somatomedin in fetal serum may reflect low levels of the somatomedin binding protein rather than an absolute deficiency of biologically active somatomedin."}
{"id": "PMID:186475", "title": "Plasma 16 beta-hydroxydehydroepiandrosterone in normal and pathological conditions in man.", "content": "Plasma 16beta-hydroxydehydroepiandrosterone (16 beta-OH-DHEA) levels in normal subjects and patients with certain pathological conditions have been evaluated using radioimmunoassay of the steroid. Plasma 16 beta-OH-DHEA levels in normal subjects rose sharply during adolescence and then declined slowly throughout adult life: 192 +/- 54 (SE) pg/ml between 7 and 11 yrs., 395 +/- 22 pg/ml between 15 and 19 yrs, 330 +/- 29 pg/ml between 20 and 39 yrs., 291 +/- 35 pg/ml between 40 and 59 yrs., and 124 +/- 20 over 60 yrs. No significant difference was found between male and female subjects. Plasma 16 beta-OH-DHEA rose significantly (P less than 0.001) during ACTH stimulation, declined significantly (P less than 0.005) during dexamethasone suppression, declined significantly (P less than 0.05) during gonadal suppression, rose significantly (P less than 0.05) during gonadal stimulation and rose significantly (P less than 0.005) after the administration of WIN 24,540, an inhibitor of 3 beta-ol-dehydrogenase. The concentration of 16 beta-OH-DHEA in adrenal venous blood was higher than in inferior vena cava blood, but 16 beta-OH-DHEA in hepatic venous blood was not higher than 16 beta-OH-DHEA in arterial blood. It is inferred that 16 beta-OH-DHEA is secreted directly by the adrenal cortex and probably the gonads. Plasma 16 beta-OH-DHEA was elevated in normal pregnant women, pregnant women with toxemia, and in patients with Cushing's disease, ectopic ACTH-producing tumor, and congenital adrenal hyperplasia, but it was not elevated in patients with low-renin essential hypertension.", "contents": "Plasma 16 beta-hydroxydehydroepiandrosterone in normal and pathological conditions in man. Plasma 16beta-hydroxydehydroepiandrosterone (16 beta-OH-DHEA) levels in normal subjects and patients with certain pathological conditions have been evaluated using radioimmunoassay of the steroid. Plasma 16 beta-OH-DHEA levels in normal subjects rose sharply during adolescence and then declined slowly throughout adult life: 192 +/- 54 (SE) pg/ml between 7 and 11 yrs., 395 +/- 22 pg/ml between 15 and 19 yrs, 330 +/- 29 pg/ml between 20 and 39 yrs., 291 +/- 35 pg/ml between 40 and 59 yrs., and 124 +/- 20 over 60 yrs. No significant difference was found between male and female subjects. Plasma 16 beta-OH-DHEA rose significantly (P less than 0.001) during ACTH stimulation, declined significantly (P less than 0.005) during dexamethasone suppression, declined significantly (P less than 0.05) during gonadal suppression, rose significantly (P less than 0.05) during gonadal stimulation and rose significantly (P less than 0.005) after the administration of WIN 24,540, an inhibitor of 3 beta-ol-dehydrogenase. The concentration of 16 beta-OH-DHEA in adrenal venous blood was higher than in inferior vena cava blood, but 16 beta-OH-DHEA in hepatic venous blood was not higher than 16 beta-OH-DHEA in arterial blood. It is inferred that 16 beta-OH-DHEA is secreted directly by the adrenal cortex and probably the gonads. Plasma 16 beta-OH-DHEA was elevated in normal pregnant women, pregnant women with toxemia, and in patients with Cushing's disease, ectopic ACTH-producing tumor, and congenital adrenal hyperplasia, but it was not elevated in patients with low-renin essential hypertension."}
{"id": "PMID:186476", "title": "The effect of ACTH and cortisol on aldosterone and cortisol clearance and distribution in plasma and whole blood.", "content": "The mechanisms of increased aldosterone and cortisol metabolic clearance rates (MCR) following ACTH or cortisol administration were studied in 13 subjects undergoing cardiac catheterization and in 9 healthy controls. In control subjects, the MCR (plasma) of both steroids increased by 29% (aldosterone: from 936 +/- 57 to 1204 +/- 55 l/day/m2, cortisol: from 205 +/- 12 to 264 +/- 17 l/day/m2 +/- SE) after ACTH (12 units/h) for 1 to 4 h, and by 20 and 32%, respectively, after cortisol (12 mg/h) for 1 to 2 h. In contrast, aldosterone MCR (whole blood) did not change with ACTH or cortisol administration (from 1276 +/- 57 to 1330 +/- 59 l/day/m2), indicating that the plasma MCR increase results from a redistribution of aldosterone from plasma to red cells. Aldosterone splanchnic extraction was 92 +/- 1% (n = 12) with normal morning cortisol levels, and extraction was unchanged after ACTH administration. For cortisol, however, the splanchnic extraction increased from 8 +/- 0.8% to 17.8 +/- 5.0%, and the MCR (whole blood) likewise increased by 15 to 31% (from 295 +/- 23 to 357 +/- 30 l/day/m2), after ACTH or cortisol administration. In vivo and in vitro measurements (at 37 C) of tracer aldosterone concentration in plasma and in red cells showed an increase in distribution to red cells with increasing cortisol concentrations. The results suggest that a fraction of aldosterone is bound in plasma and displaced by cortisol into red cells. There is an increased aldosterone plasma MCR, but unaltered whole blood MCR, since the liver extracts aldosterone almost completely from both plasma and red cells. The increase in cortisol MCR (plasma) results from both an increased splanchnic extraction as plasma binding sites approach saturation and a redistribution into red cells.", "contents": "The effect of ACTH and cortisol on aldosterone and cortisol clearance and distribution in plasma and whole blood. The mechanisms of increased aldosterone and cortisol metabolic clearance rates (MCR) following ACTH or cortisol administration were studied in 13 subjects undergoing cardiac catheterization and in 9 healthy controls. In control subjects, the MCR (plasma) of both steroids increased by 29% (aldosterone: from 936 +/- 57 to 1204 +/- 55 l/day/m2, cortisol: from 205 +/- 12 to 264 +/- 17 l/day/m2 +/- SE) after ACTH (12 units/h) for 1 to 4 h, and by 20 and 32%, respectively, after cortisol (12 mg/h) for 1 to 2 h. In contrast, aldosterone MCR (whole blood) did not change with ACTH or cortisol administration (from 1276 +/- 57 to 1330 +/- 59 l/day/m2), indicating that the plasma MCR increase results from a redistribution of aldosterone from plasma to red cells. Aldosterone splanchnic extraction was 92 +/- 1% (n = 12) with normal morning cortisol levels, and extraction was unchanged after ACTH administration. For cortisol, however, the splanchnic extraction increased from 8 +/- 0.8% to 17.8 +/- 5.0%, and the MCR (whole blood) likewise increased by 15 to 31% (from 295 +/- 23 to 357 +/- 30 l/day/m2), after ACTH or cortisol administration. In vivo and in vitro measurements (at 37 C) of tracer aldosterone concentration in plasma and in red cells showed an increase in distribution to red cells with increasing cortisol concentrations. The results suggest that a fraction of aldosterone is bound in plasma and displaced by cortisol into red cells. There is an increased aldosterone plasma MCR, but unaltered whole blood MCR, since the liver extracts aldosterone almost completely from both plasma and red cells. The increase in cortisol MCR (plasma) results from both an increased splanchnic extraction as plasma binding sites approach saturation and a redistribution into red cells."}
{"id": "PMID:186477", "title": "Spontaneous hypercortisolism without Cushing's syndrome.", "content": "A very high cortisol production rate (CPR) with elevated plasma ACTH was found in a hypertensive, hypokalemic, but otherwise healthy male patient. There were no symptoms or signs of Cushing's syndrome. The hypercortisolism appeared to be of the pituitary dependent type. During the follow-up of 36 months, no changes in outward appearance occurred, notwithstanding persistent hypercortisolism. The possibility of either Conn's syndrome or of an enzymatic defect in steroidogenesis could be ruled out. One of the three children (a healthy boy of 20 years) also showed hypertension and hypercortisolism. A possibly genetically determined hyposensitivity to the glucocorticoid action of cortisol is postulated.", "contents": "Spontaneous hypercortisolism without Cushing's syndrome. A very high cortisol production rate (CPR) with elevated plasma ACTH was found in a hypertensive, hypokalemic, but otherwise healthy male patient. There were no symptoms or signs of Cushing's syndrome. The hypercortisolism appeared to be of the pituitary dependent type. During the follow-up of 36 months, no changes in outward appearance occurred, notwithstanding persistent hypercortisolism. The possibility of either Conn's syndrome or of an enzymatic defect in steroidogenesis could be ruled out. One of the three children (a healthy boy of 20 years) also showed hypertension and hypercortisolism. A possibly genetically determined hyposensitivity to the glucocorticoid action of cortisol is postulated."}
{"id": "PMID:186478", "title": "GH, ACTH, TSH, LH, and FSH reserve in pre pubertal girls with congenital adrenal hyperplasia.", "content": "The pituitary reserve of GH, ACTH, TSH, LH, and FSH was determined in seven prepubertal birls suffering from congenital adrenal hyperplasia due to 21-hydroxylation defect and under treatment with cortisone acetate. GH and ACTH were studied during the insulin induced hypoglycemia test. The LH, FSH, and TSH reserved were assayed by means of the LH-RH and TRH tests. GH behavior proved to be similar to that found in normal subjects, whereas basal and/or after stimulus ACTH turned out to be higher than the upper limits of the normal range in five out of six girls. The mean basal value and the mean LH peak were not significantly higher than those found in normal prepubertal girls; the mean basal value and the mean FSH peak were lower than the mean of the control group. The difference is significant (P less than 0.05) only between the peak values. The mean basal TSH in the patients is significantly higher (P less than 0.01) than the mean value of the control group. The maximum TSH after TRH is not significantly different from the mean value fo the control group.", "contents": "GH, ACTH, TSH, LH, and FSH reserve in pre pubertal girls with congenital adrenal hyperplasia. The pituitary reserve of GH, ACTH, TSH, LH, and FSH was determined in seven prepubertal birls suffering from congenital adrenal hyperplasia due to 21-hydroxylation defect and under treatment with cortisone acetate. GH and ACTH were studied during the insulin induced hypoglycemia test. The LH, FSH, and TSH reserved were assayed by means of the LH-RH and TRH tests. GH behavior proved to be similar to that found in normal subjects, whereas basal and/or after stimulus ACTH turned out to be higher than the upper limits of the normal range in five out of six girls. The mean basal value and the mean LH peak were not significantly higher than those found in normal prepubertal girls; the mean basal value and the mean FSH peak were lower than the mean of the control group. The difference is significant (P less than 0.05) only between the peak values. The mean basal TSH in the patients is significantly higher (P less than 0.01) than the mean value of the control group. The maximum TSH after TRH is not significantly different from the mean value fo the control group."}
{"id": "PMID:186479", "title": "Effectiveness of cyproheptadine in decreasing plasma ACTH concentrations in Nelson's syndrome.", "content": "Cyproheptadine (24 mg q.d.) was administered to four patients with Nelson's Syndrome for a 3-5 month period. This resulted in a significant reduction in plasma ACTH and prolactin concentrations in 3 of these subjects. A rise in plasma ACTH concentrations occurred following discontinuance of medication in one patient. The results suggest that pituitary ACTH secretion in some patients with Nelson's Syndrome is under Central Nervous System control.", "contents": "Effectiveness of cyproheptadine in decreasing plasma ACTH concentrations in Nelson's syndrome. Cyproheptadine (24 mg q.d.) was administered to four patients with Nelson's Syndrome for a 3-5 month period. This resulted in a significant reduction in plasma ACTH and prolactin concentrations in 3 of these subjects. A rise in plasma ACTH concentrations occurred following discontinuance of medication in one patient. The results suggest that pituitary ACTH secretion in some patients with Nelson's Syndrome is under Central Nervous System control."}
{"id": "PMID:186480", "title": "Use of receptors in the preparation of LH-free serum.", "content": "The use of specific receptors has provided a novel method to prepare LH-free serum. LH-free serum was used in RRA to measure basal LH levels in serum of men and women during menstrual cycle as well as during post menopause.", "contents": "Use of receptors in the preparation of LH-free serum. The use of specific receptors has provided a novel method to prepare LH-free serum. LH-free serum was used in RRA to measure basal LH levels in serum of men and women during menstrual cycle as well as during post menopause."}
{"id": "PMID:186481", "title": "Modification of renin reactivity by lipids extracted from normal, hypertensive, and uremic plasma.", "content": "Plasma renin reactivity (PRR), the in vitro rate of angiotensin generation after addition of renin, is greater in plasma of hypertensive patients and uremic patients than in plasma of normotensive control subjects. To determine if this difference is due to different substrate reactivities, substrate was denatured and replaced with homologous substrate. After a 180 min incubation, PRR in normal plasma (73 ng/ml +/- 5 SE) was less (P less than 0.01) than that in hypertensive (112 ng/ml +/- 15 SE) or uremic (123 ng/ml +/- 39 SE) plasma. To determine if uremic plasma lacks a renin inhibitor, buffer or plasma was added to renin-renin substrate. Less angiotensin was generated (P less than 0.05) with normal (72 ng/ml +/- 4 SE) and uremic (88 ng/ml +/- 4 SE) plasma during 30 min than with buffer (107 ng/ml +/- 4 SE). After 180 minutes, less angiotensin was generated with normal (P less than 0.05) but not uremic plasma (P greater then 0.6), than with buffer. In vitro angiotensin generation was inhibited by lipids extracted from normal plasma. Lipids were separated into acetone soluble (neutral lipids) and acetone insoluble (phospholipid) fractions. Acetone soluble lipids, extracted from normal plasma, competitively inhibit renin: renin was not inhibited by acetone insoluble lipids. Acetone soluble lipids extracted from uremic plasma inhibited PRR to a lesser extent than lipids from either normal plasma or hypertensive plasma (P less than 0.01). Increased PRR in uremic plasma may be related to the deficiency of a circulating acetone soluble renin inhibiting factor.", "contents": "Modification of renin reactivity by lipids extracted from normal, hypertensive, and uremic plasma. Plasma renin reactivity (PRR), the in vitro rate of angiotensin generation after addition of renin, is greater in plasma of hypertensive patients and uremic patients than in plasma of normotensive control subjects. To determine if this difference is due to different substrate reactivities, substrate was denatured and replaced with homologous substrate. After a 180 min incubation, PRR in normal plasma (73 ng/ml +/- 5 SE) was less (P less than 0.01) than that in hypertensive (112 ng/ml +/- 15 SE) or uremic (123 ng/ml +/- 39 SE) plasma. To determine if uremic plasma lacks a renin inhibitor, buffer or plasma was added to renin-renin substrate. Less angiotensin was generated (P less than 0.05) with normal (72 ng/ml +/- 4 SE) and uremic (88 ng/ml +/- 4 SE) plasma during 30 min than with buffer (107 ng/ml +/- 4 SE). After 180 minutes, less angiotensin was generated with normal (P less than 0.05) but not uremic plasma (P greater then 0.6), than with buffer. In vitro angiotensin generation was inhibited by lipids extracted from normal plasma. Lipids were separated into acetone soluble (neutral lipids) and acetone insoluble (phospholipid) fractions. Acetone soluble lipids, extracted from normal plasma, competitively inhibit renin: renin was not inhibited by acetone insoluble lipids. Acetone soluble lipids extracted from uremic plasma inhibited PRR to a lesser extent than lipids from either normal plasma or hypertensive plasma (P less than 0.01). Increased PRR in uremic plasma may be related to the deficiency of a circulating acetone soluble renin inhibiting factor."}
{"id": "PMID:186482", "title": "Unconjugated dehydroepiandrosterone plasma levels in normal subjects from birth to adolescence in human: the use of a sensitive radioimmunoassay.", "content": "A specific and sensitive radioimmunoassay for measuring unconjugated plasma dehydroepiandrosterone (DHA) has been developed and the results expressed in ng/100 ml. Mean values +/-1 SD were in mixed cord blood 593.3 +/- 186.5 in 21 females and 712.7 +/- 190.9 in 18 males. During the first day of life the peripheral plasma concentration of DHA was 917.6 +/- 317.8 in 22 female and 922.65 +/- 290 in 17 male neonates. During the first month of age, DHA levels decreased significantly and then more progressively throughout the first year of life. Mean levels observed between the first and 6th month of life were 147.1 +/- 53.6 in 15 girls and 151.6 +/- 62.7 in 28 boys. Between 6 and 12 months of age mean DHA levels were 90.9 +/- 43.3 and 68.14 +/- 30.9 in 11 girls and 24 boys, respectively. In 250 normal children, plasma DHA levels were very low between 1 to 6 years of age, but rising progressively thereafter without any sex difference long before any clinical sign of puberty. A circadian rhythm parallel to that of cortisol was observed as early as 5 years of age. Acute and chronic stimulation of ACTH confirmed the adrenal origin of DHA, while the results of hCG stimulation test and fluoxymesterone suppression test assessed the testicular participation to the DHA production.", "contents": "Unconjugated dehydroepiandrosterone plasma levels in normal subjects from birth to adolescence in human: the use of a sensitive radioimmunoassay. A specific and sensitive radioimmunoassay for measuring unconjugated plasma dehydroepiandrosterone (DHA) has been developed and the results expressed in ng/100 ml. Mean values +/-1 SD were in mixed cord blood 593.3 +/- 186.5 in 21 females and 712.7 +/- 190.9 in 18 males. During the first day of life the peripheral plasma concentration of DHA was 917.6 +/- 317.8 in 22 female and 922.65 +/- 290 in 17 male neonates. During the first month of age, DHA levels decreased significantly and then more progressively throughout the first year of life. Mean levels observed between the first and 6th month of life were 147.1 +/- 53.6 in 15 girls and 151.6 +/- 62.7 in 28 boys. Between 6 and 12 months of age mean DHA levels were 90.9 +/- 43.3 and 68.14 +/- 30.9 in 11 girls and 24 boys, respectively. In 250 normal children, plasma DHA levels were very low between 1 to 6 years of age, but rising progressively thereafter without any sex difference long before any clinical sign of puberty. A circadian rhythm parallel to that of cortisol was observed as early as 5 years of age. Acute and chronic stimulation of ACTH confirmed the adrenal origin of DHA, while the results of hCG stimulation test and fluoxymesterone suppression test assessed the testicular participation to the DHA production."}
{"id": "PMID:186483", "title": "Varicella-zoster plaque assay and plaque reduction neutralization test by the immunoperoxidase technique.", "content": "A new plaque assay for the quantitation of varicella-zoster virus and a plaque reduction neutralization test for the determination of neutralizing antibody titer have been developed using the indirect immunoperoxidase technique. As compared with the classical plaque assay using a solid overlay, the test gives earlier results since plaque counting can be performed on day 3 after the inoculation of cell cultures. In six patients with zoster infection, neutralizing antibody titers ranged from 1:20 to 1:40 before the onset of infection and reached high levels (1:320 to 1:5,120) during the convalescent phase of the disease. Complement-fixing (CF) titers were all negative (less than 1:8) in prezoster serum samples from the same patients and ranged from 1:128 to 1:2,048 in the convalescent-phase sera. In the two cases in which late serum samples were available, neutralizing antibody titers matched the preillness levels, whereas CF titers dropped to undetectable levels. Neither neutralizing nor CF antibody was detected in two sera from individuals with no history of varicella-zoster infection. No differences in virus titers or neutralizing antibody titers were observed between the immunoperoxidase and the classical plaque assays. The appropriate characterization of reagent specificity is required before routine application of the test.", "contents": "Varicella-zoster plaque assay and plaque reduction neutralization test by the immunoperoxidase technique. A new plaque assay for the quantitation of varicella-zoster virus and a plaque reduction neutralization test for the determination of neutralizing antibody titer have been developed using the indirect immunoperoxidase technique. As compared with the classical plaque assay using a solid overlay, the test gives earlier results since plaque counting can be performed on day 3 after the inoculation of cell cultures. In six patients with zoster infection, neutralizing antibody titers ranged from 1:20 to 1:40 before the onset of infection and reached high levels (1:320 to 1:5,120) during the convalescent phase of the disease. Complement-fixing (CF) titers were all negative (less than 1:8) in prezoster serum samples from the same patients and ranged from 1:128 to 1:2,048 in the convalescent-phase sera. In the two cases in which late serum samples were available, neutralizing antibody titers matched the preillness levels, whereas CF titers dropped to undetectable levels. Neither neutralizing nor CF antibody was detected in two sera from individuals with no history of varicella-zoster infection. No differences in virus titers or neutralizing antibody titers were observed between the immunoperoxidase and the classical plaque assays. The appropriate characterization of reagent specificity is required before routine application of the test."}
{"id": "PMID:186484", "title": "Extracellular enzymes of the genus Bacteroides.", "content": "The extracellular production of hyaluronidase and chondroitin sulfatase was demonstrated in all of the subspecies of Bacteroides fragilis tested with the exception of B. fragilis subsp. vulgatus. Elastase was found only in one strain of B. coagulans tested. This appears to be the first report of these enzyme activities in this genus. Additional enzymes found to be produced by certain members othis genus were fibrinolysin, penicillinase, lysozyme, lecithinase, deoxyribonuclease, phosphatase, protease, and lipase.", "contents": "Extracellular enzymes of the genus Bacteroides. The extracellular production of hyaluronidase and chondroitin sulfatase was demonstrated in all of the subspecies of Bacteroides fragilis tested with the exception of B. fragilis subsp. vulgatus. Elastase was found only in one strain of B. coagulans tested. This appears to be the first report of these enzyme activities in this genus. Additional enzymes found to be produced by certain members othis genus were fibrinolysin, penicillinase, lysozyme, lecithinase, deoxyribonuclease, phosphatase, protease, and lipase."}
{"id": "PMID:186485", "title": "Functional and physicochemical studies of hemoglobin St. Louis beta 28 (B10) Leu replaced by Gln: a variant with ferric beta heme iron.", "content": "Studies have been performed on a 20-yr-old man exhibiting methemoglobinemia and a severe hemolytic anemia involving formation of Heinz bodies. This condition was due to an abnormal Hb present in the red cells of the proband: Hb St. Louis, beta 28 (B10) replaced by Gln, whose structural characteristics have been previously reported. This unstable Hb represented 30% of the total and was isolated by starch block electrophoresis at pH 8.6. Electrophoretic and spectral studies showed Hb St. Louis to be a valency hybird, alpha 2 beta 2+. The presence of hemichrome in this Hb was detected by electron paramagnetic resonance studies. During this study, an electrophoretic technique was developed that allows study of the mobility of hemichrome. Oxygen equilibria performed on purified Hb St. Louis revealed a high oxygen affinity and a markedly reduced cooperativity. The Bohr effect was normal, but the interaction of this hemoglobin with 2,3-diphosphoglycerate was decreased. The oxidation rate of Hb St. Louis was normal. Hb St. Louis was completely reduced by dithionite and ferrous citrate, and the functional properties of this reduced form were normal. In contrast, Hb St. Louis was only partially reduced by diaphorase. The mechanism of the oxidation of Hb St. Louis therefore appears to differ markedly from that postulated for other Hbs M.", "contents": "Functional and physicochemical studies of hemoglobin St. Louis beta 28 (B10) Leu replaced by Gln: a variant with ferric beta heme iron. Studies have been performed on a 20-yr-old man exhibiting methemoglobinemia and a severe hemolytic anemia involving formation of Heinz bodies. This condition was due to an abnormal Hb present in the red cells of the proband: Hb St. Louis, beta 28 (B10) replaced by Gln, whose structural characteristics have been previously reported. This unstable Hb represented 30% of the total and was isolated by starch block electrophoresis at pH 8.6. Electrophoretic and spectral studies showed Hb St. Louis to be a valency hybird, alpha 2 beta 2+. The presence of hemichrome in this Hb was detected by electron paramagnetic resonance studies. During this study, an electrophoretic technique was developed that allows study of the mobility of hemichrome. Oxygen equilibria performed on purified Hb St. Louis revealed a high oxygen affinity and a markedly reduced cooperativity. The Bohr effect was normal, but the interaction of this hemoglobin with 2,3-diphosphoglycerate was decreased. The oxidation rate of Hb St. Louis was normal. Hb St. Louis was completely reduced by dithionite and ferrous citrate, and the functional properties of this reduced form were normal. In contrast, Hb St. Louis was only partially reduced by diaphorase. The mechanism of the oxidation of Hb St. Louis therefore appears to differ markedly from that postulated for other Hbs M."}
{"id": "PMID:186486", "title": "Insulin release and cyclic AMP accumulation in response to glucose in pancreatic islets of fed and starved rats.", "content": "The dose as well as the time kinetics of insulin and adenosine-3', 5' -monophosphate (cyclic AMP) responses to glucose were compared in pancreatic islets of fed and starved rats. There was a preferential impairment of the early phase of glucose-induced insulin release in perifused islets of rats starved for 16 and 48 h. Similarly, the accumulation of 3H cyclic AMP in islets prelabeled with 3H-2-adenine was less in islets of 48 h starved than fed rats, during the first 10-min of stimulation with 26.7 mM glucose in the presence of 0.1 mM of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, whereas at 30 and 60 min 3H cyclic AMP responses to glucose were similar in fed and starved islets. Also, in 10-min incubations with glucose 3.3, 6.7, 10.0, 13.3, and 26.7 mM without and with 0.1 mM and 1.0 mM 3-isobutyl-1-methylxanthine, insulin release correlated strongly with the accumulation of 3H cyclic AMP in the islets of fed as well as starved rats. The thresholds for glucose-induced insulin and 3H cyclic AMP responses were higher and the maximal responses were lower in starved than fed islets. Preincubation of islets of 48-h starved rats with 16.7 mM glucose for 60 min corrected the impaired insulin and 3H cyclic AMP responses to glucose. Starvation-induced impairment of insulin secretory responses to glucose, and their restoration by preincubation with glucose in vitro, may represent acute regulatory effects of glucose on the adenylate cyclase-cyclic AMP system in the pancreatic beta cell.", "contents": "Insulin release and cyclic AMP accumulation in response to glucose in pancreatic islets of fed and starved rats. The dose as well as the time kinetics of insulin and adenosine-3', 5' -monophosphate (cyclic AMP) responses to glucose were compared in pancreatic islets of fed and starved rats. There was a preferential impairment of the early phase of glucose-induced insulin release in perifused islets of rats starved for 16 and 48 h. Similarly, the accumulation of 3H cyclic AMP in islets prelabeled with 3H-2-adenine was less in islets of 48 h starved than fed rats, during the first 10-min of stimulation with 26.7 mM glucose in the presence of 0.1 mM of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, whereas at 30 and 60 min 3H cyclic AMP responses to glucose were similar in fed and starved islets. Also, in 10-min incubations with glucose 3.3, 6.7, 10.0, 13.3, and 26.7 mM without and with 0.1 mM and 1.0 mM 3-isobutyl-1-methylxanthine, insulin release correlated strongly with the accumulation of 3H cyclic AMP in the islets of fed as well as starved rats. The thresholds for glucose-induced insulin and 3H cyclic AMP responses were higher and the maximal responses were lower in starved than fed islets. Preincubation of islets of 48-h starved rats with 16.7 mM glucose for 60 min corrected the impaired insulin and 3H cyclic AMP responses to glucose. Starvation-induced impairment of insulin secretory responses to glucose, and their restoration by preincubation with glucose in vitro, may represent acute regulatory effects of glucose on the adenylate cyclase-cyclic AMP system in the pancreatic beta cell."}
{"id": "PMID:186487", "title": "Inhibitory effects of hypermagnesemia on the renal action of parathyroid hormone.", "content": "Available evidence indicates that serum magnesium (Mg++) levels influence the secretion rate of parathyroid hormone (PTH). Whether serum Mg++ concentrations also modify the action of PTH on its target organs has not been definitively established. The present experiments were designed to study this possibility. The effect of infusing PTH on the urinary excretion of cyclic AMP (cAMP) and PO4= was examined in five normal dogs at two different levels of serum Mg++. At normal serum Mg++ concentrations (1.89 +/- 0.14 mg/100 ml), PTH infusion increased cAMP excretion from 1.76 +/- 0.27 to 4.87 +/- 1.00 nmol/min and fractional PO4= excretion (FEPO4) from 1.58 +/- 0.36% to 23.1 +/- 2.17%. When an identical amount of PTH was given to the same dogs at a serum Mg++ of 4.36 +/- 0.20 mg/100 ml, FEPO4 increased to only 6.02+/-1.89% and cAMP from 1.31 +/- 0.23 to 1.89 +/- 0.39 nmol/min. Identical results were obtained in thyroparathyroidectomized hypermagnesemic dogs. Increased serum Mg++ levels had no effect on the phosphaturia produced by the infusion of dibutyryl cAMP to thyroparathyroidectomized dogs. In vitro studies using rat renal cortical slices revealed a progressive decrease in cAMP production in response to PTH as the Mg++ concentrations were increased in the incubation medium. The overall results indicate that hypermagnesemia inhibits the phosphaturic response to PTH by decreasing the renal production of cAMP. Plasma magnesium, therefore, may participate in a double feedback mechanism, not only controlling the release of PTH, but also altering the biological activity of the hormone at the level of the target organ.", "contents": "Inhibitory effects of hypermagnesemia on the renal action of parathyroid hormone. Available evidence indicates that serum magnesium (Mg++) levels influence the secretion rate of parathyroid hormone (PTH). Whether serum Mg++ concentrations also modify the action of PTH on its target organs has not been definitively established. The present experiments were designed to study this possibility. The effect of infusing PTH on the urinary excretion of cyclic AMP (cAMP) and PO4= was examined in five normal dogs at two different levels of serum Mg++. At normal serum Mg++ concentrations (1.89 +/- 0.14 mg/100 ml), PTH infusion increased cAMP excretion from 1.76 +/- 0.27 to 4.87 +/- 1.00 nmol/min and fractional PO4= excretion (FEPO4) from 1.58 +/- 0.36% to 23.1 +/- 2.17%. When an identical amount of PTH was given to the same dogs at a serum Mg++ of 4.36 +/- 0.20 mg/100 ml, FEPO4 increased to only 6.02+/-1.89% and cAMP from 1.31 +/- 0.23 to 1.89 +/- 0.39 nmol/min. Identical results were obtained in thyroparathyroidectomized hypermagnesemic dogs. Increased serum Mg++ levels had no effect on the phosphaturia produced by the infusion of dibutyryl cAMP to thyroparathyroidectomized dogs. In vitro studies using rat renal cortical slices revealed a progressive decrease in cAMP production in response to PTH as the Mg++ concentrations were increased in the incubation medium. The overall results indicate that hypermagnesemia inhibits the phosphaturic response to PTH by decreasing the renal production of cAMP. Plasma magnesium, therefore, may participate in a double feedback mechanism, not only controlling the release of PTH, but also altering the biological activity of the hormone at the level of the target organ."}
{"id": "PMID:186488", "title": "The lymphocyte beta-adrenoceptor in normal subjects and patients with bronchial asthma: the effect of different forms of treatment on receptor function.", "content": "beta-Adrenoceptor function has been compared in lymphocytes of normal subjects, asthmatic patients taking large doses of beta-adrenergic bronchodilators, and comparable asthmatics treated exclusively with nonadrenergic medication. The effect of prolonged administration of beta-adrenoceptor agonists on receptor function in normal subjects has also been examined. beta-receptor response in each situation was quantitated by changes in levels of cyclic AMP, measured by a protein-binding assay. Dose response curves to isoproterenol (10 nM-0.1 mM) have been constructed for each group. Maximal increase in cyclic AMP in lymphocytes from normal subjects (393.2+/-44.0%) and in asthmatics on nonadrenergic preparations (408.3+/-46.7%) was significantly greater (P less than 0.001) than in asthmatics taking large doses of beta-sympathomimetics (67.5+/-24.2%). Depression of the cyclic AMP response appeared to correlate with the degree of exposure to beta-adrenergic agonists but not with the prevailing severity of the patient's asthma. Withdrawal of beta-adrenergic drugs was followed by a reversion of the cyclic AMP response to normal values, which suggests that the depression was drug-induced rather than an inherent feature of the disease. This interpretation was confirmed by the finding that prolonged exposure of normal subjects to high doses of a beta-adrenergic agonist caused a marked and significant (p less than 0.001) reduction in the cyclic AMP response, very similar to that seen in asthmatics on large doses of adrenergic bronchodilators. A possible link between drug-induced changes in the cyclic AMP response and the rise in the United Kingdom asthma death rate in the 1960's is discussed.", "contents": "The lymphocyte beta-adrenoceptor in normal subjects and patients with bronchial asthma: the effect of different forms of treatment on receptor function. beta-Adrenoceptor function has been compared in lymphocytes of normal subjects, asthmatic patients taking large doses of beta-adrenergic bronchodilators, and comparable asthmatics treated exclusively with nonadrenergic medication. The effect of prolonged administration of beta-adrenoceptor agonists on receptor function in normal subjects has also been examined. beta-receptor response in each situation was quantitated by changes in levels of cyclic AMP, measured by a protein-binding assay. Dose response curves to isoproterenol (10 nM-0.1 mM) have been constructed for each group. Maximal increase in cyclic AMP in lymphocytes from normal subjects (393.2+/-44.0%) and in asthmatics on nonadrenergic preparations (408.3+/-46.7%) was significantly greater (P less than 0.001) than in asthmatics taking large doses of beta-sympathomimetics (67.5+/-24.2%). Depression of the cyclic AMP response appeared to correlate with the degree of exposure to beta-adrenergic agonists but not with the prevailing severity of the patient's asthma. Withdrawal of beta-adrenergic drugs was followed by a reversion of the cyclic AMP response to normal values, which suggests that the depression was drug-induced rather than an inherent feature of the disease. This interpretation was confirmed by the finding that prolonged exposure of normal subjects to high doses of a beta-adrenergic agonist caused a marked and significant (p less than 0.001) reduction in the cyclic AMP response, very similar to that seen in asthmatics on large doses of adrenergic bronchodilators. A possible link between drug-induced changes in the cyclic AMP response and the rise in the United Kingdom asthma death rate in the 1960's is discussed."}
{"id": "PMID:186489", "title": "Bone resorption in organ culture: inhibition by the divalent cation ionophores A23187 and X-537A.", "content": "The ionophores A23187 and X-537A were used as probes to investigate the possible role of calcium uptake by bone as a mediator for the stimulation of bone resorption induced by parathyroid hormone (PTH) and other agents in cultured mouse calvaria. The ionophores alone at concentrations from 1 nM to 20 muM did not stimulate bone resorption, nor did they potentiate bone resorption stimulated by submaximal concentrations of PTH after either brief (15-60 min) or extended (1-3 day) exposure to the ionophores. Unexpectedly, we found that the ionophores inhibit in a dose-dependent manner bone resorption stimulated by PTH and a wide variety of other compounds (prostaglandin E2, 1alpha-hydroxycholecalciferol, 3-isobutyl-1-methyl-xanthine, and phorbol myristate acetate). This inhibition was not due to irreversible damage to the bones by the ionophores, because the inhibition was reversible even after 24 h of treatment. Inhibition of bone resorption by the ionophores was observed in media of both high and low calcium concentration, indicating that the inhibition was not due to a critical extracellular calcium concentration. Inhibition by the ionophores differs qualitatively in several ways from that produced by calcitonin, a natural inhibitor of bone resorption. Furthermore, A23187 at 1.0 mug/ml had no effect on the accumulation of cyclic AMP in the medium of either control, PTH- or calcitonin treated calvaria. We conclude that the ionophores A23187 or X537A do not stimulate bone resorption nor potentiate the effects of stimulators of bone resorption; instead they are inhibitors of bone resorption stimulated by a wide variety of compounds.", "contents": "Bone resorption in organ culture: inhibition by the divalent cation ionophores A23187 and X-537A. The ionophores A23187 and X-537A were used as probes to investigate the possible role of calcium uptake by bone as a mediator for the stimulation of bone resorption induced by parathyroid hormone (PTH) and other agents in cultured mouse calvaria. The ionophores alone at concentrations from 1 nM to 20 muM did not stimulate bone resorption, nor did they potentiate bone resorption stimulated by submaximal concentrations of PTH after either brief (15-60 min) or extended (1-3 day) exposure to the ionophores. Unexpectedly, we found that the ionophores inhibit in a dose-dependent manner bone resorption stimulated by PTH and a wide variety of other compounds (prostaglandin E2, 1alpha-hydroxycholecalciferol, 3-isobutyl-1-methyl-xanthine, and phorbol myristate acetate). This inhibition was not due to irreversible damage to the bones by the ionophores, because the inhibition was reversible even after 24 h of treatment. Inhibition of bone resorption by the ionophores was observed in media of both high and low calcium concentration, indicating that the inhibition was not due to a critical extracellular calcium concentration. Inhibition by the ionophores differs qualitatively in several ways from that produced by calcitonin, a natural inhibitor of bone resorption. Furthermore, A23187 at 1.0 mug/ml had no effect on the accumulation of cyclic AMP in the medium of either control, PTH- or calcitonin treated calvaria. We conclude that the ionophores A23187 or X537A do not stimulate bone resorption nor potentiate the effects of stimulators of bone resorption; instead they are inhibitors of bone resorption stimulated by a wide variety of compounds."}
{"id": "PMID:186490", "title": "Modulation of the cyclic AMP content of rat renal inner medulla by oxygen: possible role of local prostaglandins.", "content": "The lower O2 tension and more active anerobic metabolism that pertain in the inner medulla (IM) of kidney relative to cortex (C) are well recognized, but there is no evidence that O2 availability constitutes a limiting or regulatory factor in IM metabolism or function. In the present in vitro study, we examined the effects of O2 on adenosine 3',5'-monophosphate (cAMP) metabolism in slices of rat renal C and IM. After a 20-min incubation of slices in Krebs Ringer bicarbonate buffer with 95% O2 + 5% CO2 serving as the gas phase, the cAMP content of IM was 6-10 fold higher than that of C in either the presence or absence of 2 mM 1-methyl-3-isobutylxanthine in the incubation media. In slices of IM incubated for 20 min with 1-methyl-3-isobutylxanthine, cAMP was 22.5+/-SE 2.48 pmol/mg wet weight at 95% O2 and 4.37 without O2. Oxygenation of O2-deprived IM increased cAMP twofold in 2 min, an effect fully expressed in 5 min (fivefold increase). Further, cAMP of IM rose progressively and significantly over a range of atmospheric O2 content from 0 to 50% conditions which should reproduce and encompass O2 tensions that pertain in tissues in vivo. By contrast, basal cAMP content of C varied less than twofold in the presence of 95% versus no O2, implying that O2 modulation of cAMP was specific for IM. Indomethacin and meclofenamate, structurally distinct inhibitors of prostaglandin synthesis, both significantly decreased basal cAMP accumulation in oxygenated slices of IM but not of C. Meclofenamate also reduced basal adenylate cyclase activity determined in homogenates prepared from slices of IM which had been incubated at 95% O2. In slices of IM previously exposed to indomethacin or meclofenamate at 95% O2, a maximally effective concentration of exogenous prostaglandin E1 restored cAMP and adenylate cyclase activity to levels which approximated those observed at 95% O2 in the absence of an inhibitor of prostaglandin synthesis. These results suggest that O2 enhancement of cAMP content in IM may be mediated at least in part by local prostaglandins.", "contents": "Modulation of the cyclic AMP content of rat renal inner medulla by oxygen: possible role of local prostaglandins. The lower O2 tension and more active anerobic metabolism that pertain in the inner medulla (IM) of kidney relative to cortex (C) are well recognized, but there is no evidence that O2 availability constitutes a limiting or regulatory factor in IM metabolism or function. In the present in vitro study, we examined the effects of O2 on adenosine 3',5'-monophosphate (cAMP) metabolism in slices of rat renal C and IM. After a 20-min incubation of slices in Krebs Ringer bicarbonate buffer with 95% O2 + 5% CO2 serving as the gas phase, the cAMP content of IM was 6-10 fold higher than that of C in either the presence or absence of 2 mM 1-methyl-3-isobutylxanthine in the incubation media. In slices of IM incubated for 20 min with 1-methyl-3-isobutylxanthine, cAMP was 22.5+/-SE 2.48 pmol/mg wet weight at 95% O2 and 4.37 without O2. Oxygenation of O2-deprived IM increased cAMP twofold in 2 min, an effect fully expressed in 5 min (fivefold increase). Further, cAMP of IM rose progressively and significantly over a range of atmospheric O2 content from 0 to 50% conditions which should reproduce and encompass O2 tensions that pertain in tissues in vivo. By contrast, basal cAMP content of C varied less than twofold in the presence of 95% versus no O2, implying that O2 modulation of cAMP was specific for IM. Indomethacin and meclofenamate, structurally distinct inhibitors of prostaglandin synthesis, both significantly decreased basal cAMP accumulation in oxygenated slices of IM but not of C. Meclofenamate also reduced basal adenylate cyclase activity determined in homogenates prepared from slices of IM which had been incubated at 95% O2. In slices of IM previously exposed to indomethacin or meclofenamate at 95% O2, a maximally effective concentration of exogenous prostaglandin E1 restored cAMP and adenylate cyclase activity to levels which approximated those observed at 95% O2 in the absence of an inhibitor of prostaglandin synthesis. These results suggest that O2 enhancement of cAMP content in IM may be mediated at least in part by local prostaglandins."}
{"id": "PMID:186491", "title": "Renal resistance to parathyroid hormone during phosphorus deprivation.", "content": "Because previous studies have demonstrated that renal inorganic phosphate reabsorption is enhanced in rats after dietary phosphorus deprivation, we studied the effects of parathyroid hormone (PTH) upon inorganic phosphate reabsorption in acutely thyroparathyroidectomized rats stabilized on a low phosphorus diet to determine if the phosphaturic response to PTH is impaired during phosphorous depletion. Acutely thyroparathyroidectomized phosphorus-deprived rats responded only minimally to PTH, whereas similarly prepared animals stabilized on a high phosphorus diet exhibited a large phosphaturic response. Base-line urinary cyclic AMP values and PTH-induced increases in cyclic AMP excretion were similar in both groups. In other experiments, dibutyryl cyclic AMP elicited a greatly diminished phosphaturic response in phosphorus-deprived rats, as compared to their high phosphorus counterparts. These results indicate that the renal phosphaturic responses to PTH and cyclic AMP are impaired during dietary phosphorus deprivation. The impaired phosphaturia would contribute to phosphorus conservation and to the replenishment of inorganic phosphate stores after phosphorus depletion.", "contents": "Renal resistance to parathyroid hormone during phosphorus deprivation. Because previous studies have demonstrated that renal inorganic phosphate reabsorption is enhanced in rats after dietary phosphorus deprivation, we studied the effects of parathyroid hormone (PTH) upon inorganic phosphate reabsorption in acutely thyroparathyroidectomized rats stabilized on a low phosphorus diet to determine if the phosphaturic response to PTH is impaired during phosphorous depletion. Acutely thyroparathyroidectomized phosphorus-deprived rats responded only minimally to PTH, whereas similarly prepared animals stabilized on a high phosphorus diet exhibited a large phosphaturic response. Base-line urinary cyclic AMP values and PTH-induced increases in cyclic AMP excretion were similar in both groups. In other experiments, dibutyryl cyclic AMP elicited a greatly diminished phosphaturic response in phosphorus-deprived rats, as compared to their high phosphorus counterparts. These results indicate that the renal phosphaturic responses to PTH and cyclic AMP are impaired during dietary phosphorus deprivation. The impaired phosphaturia would contribute to phosphorus conservation and to the replenishment of inorganic phosphate stores after phosphorus depletion."}
{"id": "PMID:186492", "title": "Regulation of low density lipoprotein receptor activity in freshly isolated human lymphocytes.", "content": "Circulating human lymphocytes freshly isolated from venous blood of 15 normal subjects exhibited a low capacity to bind, take up, and degrade 125I-labeled low density lipoprotein (LDL). However, when these cells were incubated for 72 h in the absence of lipoproteins, they gradually acquired in increased number of high affinity cell surface receptors for LDL. The increase in the number of LDL receptors was associated with a 16-fold increase in the rate at which the cells were able to take up and degrade the lipoprotein. The LDL binding and degradation processes that developed in normal lymphocytes exhibited the following characteristics; (a) high affinity (saturation was achieved at LDL concentrations below 50 mug protein/ml); (b) specificity (unlabeled LDL was much more effective than human high density lipoprotein or other plasma proteins in competing with 125I-LDL for binding to the LDL receptor); and(c) feedback regulation (the increase in the number of LDL receptors that appeared after incubation of freshly isolated lymphocytes in lipoprotein-deficient medium was prevented by exposure of the cells to either LDL or a mixture of 25-hydroxycholesterol plus cholesterol but not to HDL). Freshly isolated lymphocytes obtaine from three subjects with the homozygous form of familial hypercholesterolemia failed to develop normal amounts of LDL receptor activity when incubated in medium devoid of lipoproteins. The current data indicate: (a) that the LDL receptors that appear on the surface of cholesterol-deprived, normal human lymphocytes are genetically identical to the previously characterized LDL receptors of cultured human fibroblasts and long-term lymphoid cells and (b) that at least one cell type in the human body, the circulating human lymphocyte, has the capacity to produce a high affinity LDL receptor that mediates the cellular uptake and degradation of plasma LDL.", "contents": "Regulation of low density lipoprotein receptor activity in freshly isolated human lymphocytes. Circulating human lymphocytes freshly isolated from venous blood of 15 normal subjects exhibited a low capacity to bind, take up, and degrade 125I-labeled low density lipoprotein (LDL). However, when these cells were incubated for 72 h in the absence of lipoproteins, they gradually acquired in increased number of high affinity cell surface receptors for LDL. The increase in the number of LDL receptors was associated with a 16-fold increase in the rate at which the cells were able to take up and degrade the lipoprotein. The LDL binding and degradation processes that developed in normal lymphocytes exhibited the following characteristics; (a) high affinity (saturation was achieved at LDL concentrations below 50 mug protein/ml); (b) specificity (unlabeled LDL was much more effective than human high density lipoprotein or other plasma proteins in competing with 125I-LDL for binding to the LDL receptor); and(c) feedback regulation (the increase in the number of LDL receptors that appeared after incubation of freshly isolated lymphocytes in lipoprotein-deficient medium was prevented by exposure of the cells to either LDL or a mixture of 25-hydroxycholesterol plus cholesterol but not to HDL). Freshly isolated lymphocytes obtaine from three subjects with the homozygous form of familial hypercholesterolemia failed to develop normal amounts of LDL receptor activity when incubated in medium devoid of lipoproteins. The current data indicate: (a) that the LDL receptors that appear on the surface of cholesterol-deprived, normal human lymphocytes are genetically identical to the previously characterized LDL receptors of cultured human fibroblasts and long-term lymphoid cells and (b) that at least one cell type in the human body, the circulating human lymphocyte, has the capacity to produce a high affinity LDL receptor that mediates the cellular uptake and degradation of plasma LDL."}
{"id": "PMID:186493", "title": "Structural and functional changes in an identified cricket neuron after separation from the soma. II. Functional changes.", "content": "Physiological and behavioural effects of separation from the soma were examined in isolated arborization and isolated axon segments of an identified motor neuron in the Polynesian field cricket, Teleogryllus oceanicus. The identified neuron, the contralateral dorsal longitudinal motor neuron of the metathoracic ganglion (CDLM), has an arborization most of which lies contralateral to its soma within the ganglion. Midline lesions in the ganglion separated CDLM into a distal segment composed of the axon and most of the arborization, and a proximal segment made up of the remaining arborization, neurite and soma. Isolated axonal segments were produced by cutting the nerve containing the CDLM axon. The function of the neuron-muscle system composed of CDLM, its pre-synaptic inputs, and its innervated muscle bundle was examined in contrl and experimentally operated animals. Extracellular recording assessed function in the axon. Electrical or tactil stimulation was used to excite pre-synaptic inputs to the CDLM arborization. Intracellular recording determined changes in post-synaptic potentials and miniature end-plate potentials in the muscle bundle innervated by CDLM. Normal axonal conduction, competence to respond to pre-synaptic input, neuron-muscle transmission, and miniature end-plate potential appearance can remain in the isolated arborization preparation. Physiological viability is longer in the cricket isolated arborization than in other insect distal segments described. Survival times of axonal conduction and the competence of the isolated arborization to respond to pre-synaptic input are roughly correlated with disappearance of the whole distal segment at 100 or more postoperative days. A naturally-occurring breakdown of the metathoracic dorsal longitudinal muscles in Teleogryllus eventually prevents measurements of post-synaptic potentials and miniature end-plate potentials. Normal post-synaptic function mediated by the distal arborization is maintained up to this breakdown, to a maximum of 44 days postoperative. The distal axonal segment of CDLM degenerates physiologically within four days postoperative, a time course approximating that of degeneration in vertebrate peripheral nerve distal axons.", "contents": "Structural and functional changes in an identified cricket neuron after separation from the soma. II. Functional changes. Physiological and behavioural effects of separation from the soma were examined in isolated arborization and isolated axon segments of an identified motor neuron in the Polynesian field cricket, Teleogryllus oceanicus. The identified neuron, the contralateral dorsal longitudinal motor neuron of the metathoracic ganglion (CDLM), has an arborization most of which lies contralateral to its soma within the ganglion. Midline lesions in the ganglion separated CDLM into a distal segment composed of the axon and most of the arborization, and a proximal segment made up of the remaining arborization, neurite and soma. Isolated axonal segments were produced by cutting the nerve containing the CDLM axon. The function of the neuron-muscle system composed of CDLM, its pre-synaptic inputs, and its innervated muscle bundle was examined in contrl and experimentally operated animals. Extracellular recording assessed function in the axon. Electrical or tactil stimulation was used to excite pre-synaptic inputs to the CDLM arborization. Intracellular recording determined changes in post-synaptic potentials and miniature end-plate potentials in the muscle bundle innervated by CDLM. Normal axonal conduction, competence to respond to pre-synaptic input, neuron-muscle transmission, and miniature end-plate potential appearance can remain in the isolated arborization preparation. Physiological viability is longer in the cricket isolated arborization than in other insect distal segments described. Survival times of axonal conduction and the competence of the isolated arborization to respond to pre-synaptic input are roughly correlated with disappearance of the whole distal segment at 100 or more postoperative days. A naturally-occurring breakdown of the metathoracic dorsal longitudinal muscles in Teleogryllus eventually prevents measurements of post-synaptic potentials and miniature end-plate potentials. Normal post-synaptic function mediated by the distal arborization is maintained up to this breakdown, to a maximum of 44 days postoperative. The distal axonal segment of CDLM degenerates physiologically within four days postoperative, a time course approximating that of degeneration in vertebrate peripheral nerve distal axons."}
{"id": "PMID:186497", "title": "Ultrastructural study of cylindroma (Poncet-Spiegler tumor).", "content": "This report describes the ultrastructural characteristics of a Poncet-Spiegler tumor (cylindroma, turban tumor). This tumor was made up of two cell types and showed a ductal differentiation. Cells bordering duct-like structures were joined together by innumerable desmosomes, especially in places where the cell membranes were markedly invaginated. The arguments in favor of an eccrine or an apocrine for the origin of this sweat gland tumor are discussed.", "contents": "Ultrastructural study of cylindroma (Poncet-Spiegler tumor). This report describes the ultrastructural characteristics of a Poncet-Spiegler tumor (cylindroma, turban tumor). This tumor was made up of two cell types and showed a ductal differentiation. Cells bordering duct-like structures were joined together by innumerable desmosomes, especially in places where the cell membranes were markedly invaginated. The arguments in favor of an eccrine or an apocrine for the origin of this sweat gland tumor are discussed."}
{"id": "PMID:186533", "title": "[Stick-plaque test--an economic method of quantitative determination of viruses].", "content": "An economic method for quantitative assay of viruses is presented. In this \"canule stick-plaque test\" (German abbreviation SPT) samples of viruses, geometrically diluted and taken up by a canule, are inoculated by sticking into monolayer cell cultures overlayed with agar medium. A plaquelike CPE detectable by neutral red staining develops in the area of the inoculation. The frequency of this CPE formation depends on the concentration of viruses in the inoculated dilution. This dose-response allows calculation of the ID50. In this way it is possible to carry out titration involving 6 dilutions and 10 inoculations per dilution using 3 common Petri dishes (6 cm in diameter), only. The sensitivity, accuracy, and reproductibility of this method are described and discussed.", "contents": "[Stick-plaque test--an economic method of quantitative determination of viruses]. An economic method for quantitative assay of viruses is presented. In this \"canule stick-plaque test\" (German abbreviation SPT) samples of viruses, geometrically diluted and taken up by a canule, are inoculated by sticking into monolayer cell cultures overlayed with agar medium. A plaquelike CPE detectable by neutral red staining develops in the area of the inoculation. The frequency of this CPE formation depends on the concentration of viruses in the inoculated dilution. This dose-response allows calculation of the ID50. In this way it is possible to carry out titration involving 6 dilutions and 10 inoculations per dilution using 3 common Petri dishes (6 cm in diameter), only. The sensitivity, accuracy, and reproductibility of this method are described and discussed."}
{"id": "PMID:186534", "title": "Replication of herpes simplex virus in mouse spleen cell cultures stimulated by lipopolysaccharide.", "content": "Replication of HSV was demonstrated in spleen cell cultures of D2 and several other strains of mice after prestimulation with mitogenic doses of LPS for 2 days. No viral replication occurred in unstimulated cultures or in cultures prestimulated with PHA and Con A, whereas there was some viral replication in spleen cell cultures of D2 mice after prestimulation with Poly I-C. Spleen cells of B6 mice did not support replication of HSV under any of the conditions we have tested thus far. The reasons for this defect are not clear, but it was obviously not caused by a defective lymphoproliferative response to LPS or by an active anti-viral principle elaborated by B6 spleen cells. F1 hybrids between B6 and D2 mice were capable of HSV replication to the same extent as were spleen cells of D2 mice. Several strains of both HSV-1 and HSV-2 could be replicated in D2 spleen cells cultures. Nylon column treatment of D2 spleen cells removed the ability to replicate HSV, whereas macrophage removal from the spleens by plastic adherence was without effect. Purified peritoneal exudate cells from D2 mice did not support replication of HSV. Together these data suggest that B cells activated by LPS represent the target cell of HSV replication in mouse spleen cell cultures.", "contents": "Replication of herpes simplex virus in mouse spleen cell cultures stimulated by lipopolysaccharide. Replication of HSV was demonstrated in spleen cell cultures of D2 and several other strains of mice after prestimulation with mitogenic doses of LPS for 2 days. No viral replication occurred in unstimulated cultures or in cultures prestimulated with PHA and Con A, whereas there was some viral replication in spleen cell cultures of D2 mice after prestimulation with Poly I-C. Spleen cells of B6 mice did not support replication of HSV under any of the conditions we have tested thus far. The reasons for this defect are not clear, but it was obviously not caused by a defective lymphoproliferative response to LPS or by an active anti-viral principle elaborated by B6 spleen cells. F1 hybrids between B6 and D2 mice were capable of HSV replication to the same extent as were spleen cells of D2 mice. Several strains of both HSV-1 and HSV-2 could be replicated in D2 spleen cells cultures. Nylon column treatment of D2 spleen cells removed the ability to replicate HSV, whereas macrophage removal from the spleens by plastic adherence was without effect. Purified peritoneal exudate cells from D2 mice did not support replication of HSV. Together these data suggest that B cells activated by LPS represent the target cell of HSV replication in mouse spleen cell cultures."}
{"id": "PMID:186535", "title": "Stimulation of immune mechanisms against mammary tumors by incomplete T cell depletion.", "content": "When BALB/cfC3H females are subjected to continous suction thymectomy, a procedure that results in retention of thymic remnants, the latent period before tumor development is significantly prolonged. However, when BALB/cfC3H females are thymectomized by control suction, a procedure which removes thymic lobes completely, there is no effect on mammary tumorigenesis. Our results show that incomplete T cell depletion causes premature onset of non-T cell cytotoxicity, an augmentation of T cell cytotoxicity, and an alteration in a serum-blocking activity to mammary tumor target cells as tested in microcytotoxicity assay. On the other hand, complete neonatal thymectomy effectively and completely abrogates immune response to mammary tumor target cells. The inability of completely thymectomized mice to generate an immune response to MTV suggests (but does not prove) that MTV-induced mammary tumor target cell surface antigens are thymus-dependent.", "contents": "Stimulation of immune mechanisms against mammary tumors by incomplete T cell depletion. When BALB/cfC3H females are subjected to continous suction thymectomy, a procedure that results in retention of thymic remnants, the latent period before tumor development is significantly prolonged. However, when BALB/cfC3H females are thymectomized by control suction, a procedure which removes thymic lobes completely, there is no effect on mammary tumorigenesis. Our results show that incomplete T cell depletion causes premature onset of non-T cell cytotoxicity, an augmentation of T cell cytotoxicity, and an alteration in a serum-blocking activity to mammary tumor target cells as tested in microcytotoxicity assay. On the other hand, complete neonatal thymectomy effectively and completely abrogates immune response to mammary tumor target cells. The inability of completely thymectomized mice to generate an immune response to MTV suggests (but does not prove) that MTV-induced mammary tumor target cell surface antigens are thymus-dependent."}
{"id": "PMID:186536", "title": "Natural immunity in cats to feline leukemia viral antigens.", "content": "An isotopic antiglobulin assay was developed to measure antibodies in \"normal\" cats to FOCMA, a cell surface antigen associated with immunity to FeLV-induced tumors. The assay was shown to be specific for detecting FOCMA antibody by several criteria including a correlation with cell membrane immunofluorescence and absorption tests. Antibody to FOCMA developed following FeLV infection and was expressed in heterologous species. In combination with an assay for antibody to FeLV p30, the major virion structural protein, 200 cats sera from three different geographic areas were examined for evidences of FeLV-type-C-virus infection. Approximately 17% of all sera examined contained antibody to FOCMA. Antibodies directed to the FeLV p30 were detected in 8 of the sera and only in cats with FOCMA antibody. The correlation in cat sera between antibody to FOCMA and FeLV p30 antigen suggests that both are associated with the same process, infection with FeLV type-C-virus. The relationship of the observed pattern of antibody response is discussed in relation to other horizontally transmitted RNA-containing viruses.", "contents": "Natural immunity in cats to feline leukemia viral antigens. An isotopic antiglobulin assay was developed to measure antibodies in \"normal\" cats to FOCMA, a cell surface antigen associated with immunity to FeLV-induced tumors. The assay was shown to be specific for detecting FOCMA antibody by several criteria including a correlation with cell membrane immunofluorescence and absorption tests. Antibody to FOCMA developed following FeLV infection and was expressed in heterologous species. In combination with an assay for antibody to FeLV p30, the major virion structural protein, 200 cats sera from three different geographic areas were examined for evidences of FeLV-type-C-virus infection. Approximately 17% of all sera examined contained antibody to FOCMA. Antibodies directed to the FeLV p30 were detected in 8 of the sera and only in cats with FOCMA antibody. The correlation in cat sera between antibody to FOCMA and FeLV p30 antigen suggests that both are associated with the same process, infection with FeLV type-C-virus. The relationship of the observed pattern of antibody response is discussed in relation to other horizontally transmitted RNA-containing viruses."}
{"id": "PMID:186537", "title": "Use of silica to identify host mechanisms involved in suppression of established Friend virus leukemia.", "content": "Silica, an agent predominantly toxic for macrophages, inoculated i.v. to Friend leukemia virus (FLV)-infected mice, blocks the FLV-leukemosuppressive effects of chlorite-oxidized oxyamylose (COAM)-statolon treatment. FLV-infected, COAM-statolon-treated mice that have received silica and have failed to suppress FLV leukemia produced normal amounts of interferon, but did not make antibodies cytotoxic for FLV leukemic cells. Transfer of untreated spleen cells, splenic T cells, or thymocytes from mice with suppressed FLV erythroleukemia to FLV-infected mice treated with silica and COAM-statolon restores the humoral immune response to FLV antigens and results in leukemosuppression. Thus, T lymphocytes from mice with suppressed erythroleukemia participate in FLV leukemosuppression either directly as effector cells, or indirectly as helper cell in the production of antibodies to FLV antigens.", "contents": "Use of silica to identify host mechanisms involved in suppression of established Friend virus leukemia. Silica, an agent predominantly toxic for macrophages, inoculated i.v. to Friend leukemia virus (FLV)-infected mice, blocks the FLV-leukemosuppressive effects of chlorite-oxidized oxyamylose (COAM)-statolon treatment. FLV-infected, COAM-statolon-treated mice that have received silica and have failed to suppress FLV leukemia produced normal amounts of interferon, but did not make antibodies cytotoxic for FLV leukemic cells. Transfer of untreated spleen cells, splenic T cells, or thymocytes from mice with suppressed FLV erythroleukemia to FLV-infected mice treated with silica and COAM-statolon restores the humoral immune response to FLV antigens and results in leukemosuppression. Thus, T lymphocytes from mice with suppressed erythroleukemia participate in FLV leukemosuppression either directly as effector cells, or indirectly as helper cell in the production of antibodies to FLV antigens."}
{"id": "PMID:186538", "title": "Trypsin-induced increase in intracellular cyclic AMP of lymphocytes.", "content": "Trypsin increases intracellular levels of cylic AMP (cAMP) in lymphocytes. The trypsin-induced increase in cAMP is blocked by specific trypsin inhibitors and by high concentrations of different proteins. Several proteolytic enzymes from various sources, including other pancreatic proteases, do not cause an increase in cAMP under the same experimental conditions. Immobilized trypsin induced the same increase in cAMP as does free trypsin. The trypsin-induced rise in cAMP is not due to inhibition of cAMP phosphodiesterase, but consistent activation of adenylate cyclase by trypsin could not be demonstrated. The extent of the trypsin-induced increase in intracellular cAMP correlates with the type of the lymphocyte and with the state of maturity attained by the cells. Transformed lymphocytes and nonlymphoid cells do not react at all.", "contents": "Trypsin-induced increase in intracellular cyclic AMP of lymphocytes. Trypsin increases intracellular levels of cylic AMP (cAMP) in lymphocytes. The trypsin-induced increase in cAMP is blocked by specific trypsin inhibitors and by high concentrations of different proteins. Several proteolytic enzymes from various sources, including other pancreatic proteases, do not cause an increase in cAMP under the same experimental conditions. Immobilized trypsin induced the same increase in cAMP as does free trypsin. The trypsin-induced rise in cAMP is not due to inhibition of cAMP phosphodiesterase, but consistent activation of adenylate cyclase by trypsin could not be demonstrated. The extent of the trypsin-induced increase in intracellular cAMP correlates with the type of the lymphocyte and with the state of maturity attained by the cells. Transformed lymphocytes and nonlymphoid cells do not react at all."}
{"id": "PMID:186539", "title": "Immunity to virus-free syngeneic tumor cell transplantation in the BALB/c mouse after immunization with homologous tumor cells infected with type C virus.", "content": "Syngeneic tumor cell lines free of endogenous type C virus or viral antigen antigen expression were derived from spontaneously occurring tumors of the BALB/cCr mouse. Two cell lines free of endogenous type C virus were examined and found to be highly tumorigenic in tumor growth kinetic studies. In vitro inoculation of these cell lines with Rauscher-murine leukemia virus (R-MuLV) resulted in their chronic infection in which 95 to 100% of the cells were scored as virus positive. These infected lines showed a highly significant increase in their immunogenicity as compared to their uninfected controls. Animals in which these virus-positive tumors regressed were then shown to be highly resistant to challenge with the uninfected tumor cell lines as well as to live R-MuLV. This observed resistance to uninfected tumor cell lines could not be induced by immunization of the mouse with uninfected tumor cells and R-MuLV simultaneously at the same injection site, nor could it be induced with lethally irradiated virus-infected tumor cells, subtumorigenic doses of uninfected cells, or inactivated R-MuLV or Gross leukemia virus (G-MuLV). Cell-mediated cytotoxicity studies revealed that spleen cells obtained from animals whose virus-infected tumors regressed were cytotoxic to homologous infected and uninfected tumor cells as well as to other uninfected tumor cell lines syngeneic to the BALB/c mouse. Correlation of in vitro cytotoxicity with in vivo immunity was provided by the Winn assay, by inoculation into susceptible mice of immune and nonimmune spleen cells premixed with uninfected tumor cells. The immune cells were highly effective in preventing this tumor cell transplantation. It was concluded that type-C virus infection of these syngeneic tumor cells resulted in their acquiring strong transplantation antigens that were in part due to the virion, but were at least in part due to alterations of antigens or haptens that are present in a less immunogenic form on the uninfected tumor cell.", "contents": "Immunity to virus-free syngeneic tumor cell transplantation in the BALB/c mouse after immunization with homologous tumor cells infected with type C virus. Syngeneic tumor cell lines free of endogenous type C virus or viral antigen antigen expression were derived from spontaneously occurring tumors of the BALB/cCr mouse. Two cell lines free of endogenous type C virus were examined and found to be highly tumorigenic in tumor growth kinetic studies. In vitro inoculation of these cell lines with Rauscher-murine leukemia virus (R-MuLV) resulted in their chronic infection in which 95 to 100% of the cells were scored as virus positive. These infected lines showed a highly significant increase in their immunogenicity as compared to their uninfected controls. Animals in which these virus-positive tumors regressed were then shown to be highly resistant to challenge with the uninfected tumor cell lines as well as to live R-MuLV. This observed resistance to uninfected tumor cell lines could not be induced by immunization of the mouse with uninfected tumor cells and R-MuLV simultaneously at the same injection site, nor could it be induced with lethally irradiated virus-infected tumor cells, subtumorigenic doses of uninfected cells, or inactivated R-MuLV or Gross leukemia virus (G-MuLV). Cell-mediated cytotoxicity studies revealed that spleen cells obtained from animals whose virus-infected tumors regressed were cytotoxic to homologous infected and uninfected tumor cells as well as to other uninfected tumor cell lines syngeneic to the BALB/c mouse. Correlation of in vitro cytotoxicity with in vivo immunity was provided by the Winn assay, by inoculation into susceptible mice of immune and nonimmune spleen cells premixed with uninfected tumor cells. The immune cells were highly effective in preventing this tumor cell transplantation. It was concluded that type-C virus infection of these syngeneic tumor cells resulted in their acquiring strong transplantation antigens that were in part due to the virion, but were at least in part due to alterations of antigens or haptens that are present in a less immunogenic form on the uninfected tumor cell."}
{"id": "PMID:186540", "title": "Cytomegalovirus infection in weanling guinea pigs.", "content": "Cytomegalovirus (CMV) infection of weanling guinea pigs was studied after subcutaneous and intracerebral inoculation of virus. No clinical illness appeared by day 24 after subcutaneous inoculation, even though animals developed persisting infection in many tissues, with marked variation in histogogic expression. Virus was obtained in higher titer from homogenates of salivary gland and thymus tissue. In other organs, including the brain, virus was found only be cocultivation of trypsinized liver tissue cells with guinea pig embryo cells. Appearance of virus in tissue culture was sometimes delayed for more than a month. After intracerebral inoculation, multifocal inclusion cell encephalitis developed, with spread of virus to other organs. Histologically this condition resembled findings in renal transplant patients with CMV infection. The study of CMV infection in guinea pigs may yield information applicable to human CMV infection.", "contents": "Cytomegalovirus infection in weanling guinea pigs. Cytomegalovirus (CMV) infection of weanling guinea pigs was studied after subcutaneous and intracerebral inoculation of virus. No clinical illness appeared by day 24 after subcutaneous inoculation, even though animals developed persisting infection in many tissues, with marked variation in histogogic expression. Virus was obtained in higher titer from homogenates of salivary gland and thymus tissue. In other organs, including the brain, virus was found only be cocultivation of trypsinized liver tissue cells with guinea pig embryo cells. Appearance of virus in tissue culture was sometimes delayed for more than a month. After intracerebral inoculation, multifocal inclusion cell encephalitis developed, with spread of virus to other organs. Histologically this condition resembled findings in renal transplant patients with CMV infection. The study of CMV infection in guinea pigs may yield information applicable to human CMV infection."}
{"id": "PMID:186541", "title": "Clinical trials of immunization with the Towne 125 strain of human cytomegalovirus.", "content": "The Towne 125 strain of human cytomegalovirus (CMV), adapted to growth in human diploid cell strain WI-38 and propagated in this cell line for 129 consecutive passages, was administered to male volunteers with or without preexisting antibodies to CMV. Infection was not achieved by intranasal administration. In contrast, subcutaneous inoculation of virus induced seroconversion in all seronegative volunteers and a booster antibody response in some previously seropositive individuals. Transient local reactions occured at the site of inoculation of the virus, but systemic symptoms and signs of disease were notably absent.", "contents": "Clinical trials of immunization with the Towne 125 strain of human cytomegalovirus. The Towne 125 strain of human cytomegalovirus (CMV), adapted to growth in human diploid cell strain WI-38 and propagated in this cell line for 129 consecutive passages, was administered to male volunteers with or without preexisting antibodies to CMV. Infection was not achieved by intranasal administration. In contrast, subcutaneous inoculation of virus induced seroconversion in all seronegative volunteers and a booster antibody response in some previously seropositive individuals. Transient local reactions occured at the site of inoculation of the virus, but systemic symptoms and signs of disease were notably absent."}
{"id": "PMID:186544", "title": "The effects of colestipol on the metabolism of very-low-density lipoproteins in man.", "content": "Bile acid-binding resins, currently used for the treatment of Type II hyperlipoproteinemia, decrease LDL cholesterol by 25 to 35 per cent. Elevations of plasma triglycerides sometimes occur with resin therapy, suggesting that alterations in metabolism may not be confined solely to LDL. To characterize the effects of the resins on lipoproteins in greater detail, we carried out two studies using colestipol. In the acute study, seven Type IIA patients were studied on a metabolic ward before and for the first 7 to 10 days after initiation of therapy. Blood samples were drawn after 12 to 14 hour fasts every 1 to 3 days during hospitalization and at frequent intervals thereafter for the first 2 to 6 months of therapy. In the chronic study, 12 Type II patients were studied as outpatients at monthly intervals. Three fasting plasma samples were obtained before therapy and three additional samples were ovtained between 3 and 12 months after commencement of treatment. Lipoprotein quantification of individual plasma samples was performed by combined ultracentrifugal and MnCl2-heparin precipitation techniques. The size distribution of ultracentrifugally isolated VLDL was assessed by column chromatography in Sepharose 2B. In the acute study, LDL-Chol fell 24 to 28 hours after initiation of therapy in each subject. Concomitantly, VLDL-TG rose. By days 5 to 8, mean LDL-Chol of the group had fallen by 30 per cent and mean VLDL-TG had risen by 35 per cent. Although mean VLDL-Chol also rose (by about 14 per cent), since VLDL-TG rose more, VLDL became enriched with respect to TG. At peak triglyceridemia, LDL and HDL were also found to be relatively TG-enriched. Between 7 and 30 days after initiation of therapy, VLDL-TG levels returned to and below baseline as LDL-Chol continued to fall. LDL and HDL compositions also returned toward baseline. On gel filtration chromatography of VLDL, obtained during therapy, a peak, which was not present in baseline samples, appeared in the void volume of the column. The amounts of VLDL eluting in the usual positions were also increased. Thus, acute therapy was accompanied by (1) transient rises in levels of triglyceride-enriched VLDL of apparently larger size, (2) falls in LDL-Chol, and (3) changes in the composition of LDL and HDL. In the chronic study, mean total-Chol fell from 345 to 258 mg. per deciliter and mean LDL-Chol fell from 277 to 188 mg. per deciliter (p less than 0.001 for both comparisons). Total-TG and VLDL-TG were not significantly altered. The compositions of VLDL and HDL were unchanged from pretreatment values while LDL became relatively TG-enriched. These findings suggest that acutely colestipol produced alterations in the metabolism of all lipoproteins, but that with prolonged therapy, the levels of VLDL and HDL returned toward pretreatment levels.", "contents": "The effects of colestipol on the metabolism of very-low-density lipoproteins in man. Bile acid-binding resins, currently used for the treatment of Type II hyperlipoproteinemia, decrease LDL cholesterol by 25 to 35 per cent. Elevations of plasma triglycerides sometimes occur with resin therapy, suggesting that alterations in metabolism may not be confined solely to LDL. To characterize the effects of the resins on lipoproteins in greater detail, we carried out two studies using colestipol. In the acute study, seven Type IIA patients were studied on a metabolic ward before and for the first 7 to 10 days after initiation of therapy. Blood samples were drawn after 12 to 14 hour fasts every 1 to 3 days during hospitalization and at frequent intervals thereafter for the first 2 to 6 months of therapy. In the chronic study, 12 Type II patients were studied as outpatients at monthly intervals. Three fasting plasma samples were obtained before therapy and three additional samples were ovtained between 3 and 12 months after commencement of treatment. Lipoprotein quantification of individual plasma samples was performed by combined ultracentrifugal and MnCl2-heparin precipitation techniques. The size distribution of ultracentrifugally isolated VLDL was assessed by column chromatography in Sepharose 2B. In the acute study, LDL-Chol fell 24 to 28 hours after initiation of therapy in each subject. Concomitantly, VLDL-TG rose. By days 5 to 8, mean LDL-Chol of the group had fallen by 30 per cent and mean VLDL-TG had risen by 35 per cent. Although mean VLDL-Chol also rose (by about 14 per cent), since VLDL-TG rose more, VLDL became enriched with respect to TG. At peak triglyceridemia, LDL and HDL were also found to be relatively TG-enriched. Between 7 and 30 days after initiation of therapy, VLDL-TG levels returned to and below baseline as LDL-Chol continued to fall. LDL and HDL compositions also returned toward baseline. On gel filtration chromatography of VLDL, obtained during therapy, a peak, which was not present in baseline samples, appeared in the void volume of the column. The amounts of VLDL eluting in the usual positions were also increased. Thus, acute therapy was accompanied by (1) transient rises in levels of triglyceride-enriched VLDL of apparently larger size, (2) falls in LDL-Chol, and (3) changes in the composition of LDL and HDL. In the chronic study, mean total-Chol fell from 345 to 258 mg. per deciliter and mean LDL-Chol fell from 277 to 188 mg. per deciliter (p less than 0.001 for both comparisons). Total-TG and VLDL-TG were not significantly altered. The compositions of VLDL and HDL were unchanged from pretreatment values while LDL became relatively TG-enriched. These findings suggest that acutely colestipol produced alterations in the metabolism of all lipoproteins, but that with prolonged therapy, the levels of VLDL and HDL returned toward pretreatment levels."}
{"id": "PMID:186545", "title": "Longevity syndromes: familial hypobeta and familial hyperalpha lipoproteinemia.", "content": "Longevity and morbidity and death from myocardial infarction were examined in eight kindreds with familial hypobeta lipoproteinemia and in 18 kindreds with familial hyperalpha lipoproteinemia. Expectation of life for males and females from kindreds with hypobeta lipoproteinemia was 9 and 12 years longer (p less than or equal to 0.002) than that indicated by population statistics for U.S. white populations, whereas expectation of life for males and females from kindreds with hyperalpha lipoproteinemia was 5 and 7 years longer (p less than 0.02). Morbidity from myocardial infarction in 115 living first-degree adult relatives of probands with hypobeta and hyperalpha lipoproteinemia and in 364 living first-degree adult relatives of normolipemic spouse controls were compared. Nonfatal myocardial infarction (MI) was reported for 18 of 364 (5 per cent) relatives of normal spouse controls and in 0 of 115 relatives of hypobeta and hyperalpha subjects (p less than 0.05). The ratios (mean+/-S.E.) of C-LDL to C-HDL in familial hypobeta and hyperalpha lipoproteinemia were 0.79+/-0.06 and 1.21+/-0.06, as compared to 2.41+/-0.12 in a control population (p less than 0.001). If high-density lipoproteins confer protection against development of atherosclerosis, whereas low-density lipoproteins have opposite effects, then we speculate that the low ratio of C-LDL:C-HDL may be related to prolonged longevity and decreased morbidity from myocardial infarction in familial hypobeta and hyperalpha lipoproteinemia.", "contents": "Longevity syndromes: familial hypobeta and familial hyperalpha lipoproteinemia. Longevity and morbidity and death from myocardial infarction were examined in eight kindreds with familial hypobeta lipoproteinemia and in 18 kindreds with familial hyperalpha lipoproteinemia. Expectation of life for males and females from kindreds with hypobeta lipoproteinemia was 9 and 12 years longer (p less than or equal to 0.002) than that indicated by population statistics for U.S. white populations, whereas expectation of life for males and females from kindreds with hyperalpha lipoproteinemia was 5 and 7 years longer (p less than 0.02). Morbidity from myocardial infarction in 115 living first-degree adult relatives of probands with hypobeta and hyperalpha lipoproteinemia and in 364 living first-degree adult relatives of normolipemic spouse controls were compared. Nonfatal myocardial infarction (MI) was reported for 18 of 364 (5 per cent) relatives of normal spouse controls and in 0 of 115 relatives of hypobeta and hyperalpha subjects (p less than 0.05). The ratios (mean+/-S.E.) of C-LDL to C-HDL in familial hypobeta and hyperalpha lipoproteinemia were 0.79+/-0.06 and 1.21+/-0.06, as compared to 2.41+/-0.12 in a control population (p less than 0.001). If high-density lipoproteins confer protection against development of atherosclerosis, whereas low-density lipoproteins have opposite effects, then we speculate that the low ratio of C-LDL:C-HDL may be related to prolonged longevity and decreased morbidity from myocardial infarction in familial hypobeta and hyperalpha lipoproteinemia."}
{"id": "PMID:186547", "title": "Effects of catecholamines on the lipolysis of two kinds of fat cells from adult rabbit.", "content": "The administration of various catecholamines and adrenocorticotropic hormone to adult rabbit elevated plasma glycerol concentration. These catecholamines also induced the in vitro lipolysis of isolated interscapular fat cells but could not bring about the lipolysis of epididymal ones, while adrenocorticotropic hormone induced the lipolyses of both kinds of fat cells. It may be speculated from these results that catecholamines liberated endogenously in adult rabbit cannot act on all systemic adipose tissues but have lipolytic effects on a part of them.", "contents": "Effects of catecholamines on the lipolysis of two kinds of fat cells from adult rabbit. The administration of various catecholamines and adrenocorticotropic hormone to adult rabbit elevated plasma glycerol concentration. These catecholamines also induced the in vitro lipolysis of isolated interscapular fat cells but could not bring about the lipolysis of epididymal ones, while adrenocorticotropic hormone induced the lipolyses of both kinds of fat cells. It may be speculated from these results that catecholamines liberated endogenously in adult rabbit cannot act on all systemic adipose tissues but have lipolytic effects on a part of them."}
{"id": "PMID:186548", "title": "Phospholipid removal during degradation of rat plasma very low density lipoprotein in vitro.", "content": "The hydrolysis of glycerophospholipids in very low density lipoprotein by enzyme(s) released into circulation after the injection of heparin to rats was studied. [32P]Lysolecithin was formed rapidly from [32P]lecithin when very low density lipoprotein, labeled biosynthetically with 32P, was incubated with postheparin plasma. The [32P]lysolecithin was associated with the plasma protein fraction of density greater than 1.21 g/ml, whereas [32P]lecithin exchanged between very low and high density lipoproteins. Inhibition of the plasma lecithin: cholesterol acyl transferase activity did not change the excess [32P]lysolecithin formation in postheparin plasma, and only a negligible amount of radioactivity was associated with blood cells when the incubation was repeated in whole blood. Analysis of the results has demonstrated that phospholipids are removed from VLDL by two pathways: hydrolysis of glycerophospholipids by the heparin-releasable phospholipase activity (greater than50%) and transfer to high density lipoproteins (less than50%). The tissue origin of the postheparin phospholipase was studied in plasma obtained from intact rats and supradiaphragmatic rats using specific inhibitors of the extrahepatic lipase system (protamine sulfate and 0.5 M NaCl). The phospholipase activity could be ascribed to both the hepatic and extrahepatic lipase systems. It is concluded that hydrolysis of glycerophospholipids is the major mechanism responsible for the removal of phospholipids from very low density lipoprotein during the degradation of the lipoprotein. It is suggested that phospholipid hydrolysis occurs concomitantly with triglyceride hydrolysis, predominantly in extrahepatic tissues.", "contents": "Phospholipid removal during degradation of rat plasma very low density lipoprotein in vitro. The hydrolysis of glycerophospholipids in very low density lipoprotein by enzyme(s) released into circulation after the injection of heparin to rats was studied. [32P]Lysolecithin was formed rapidly from [32P]lecithin when very low density lipoprotein, labeled biosynthetically with 32P, was incubated with postheparin plasma. The [32P]lysolecithin was associated with the plasma protein fraction of density greater than 1.21 g/ml, whereas [32P]lecithin exchanged between very low and high density lipoproteins. Inhibition of the plasma lecithin: cholesterol acyl transferase activity did not change the excess [32P]lysolecithin formation in postheparin plasma, and only a negligible amount of radioactivity was associated with blood cells when the incubation was repeated in whole blood. Analysis of the results has demonstrated that phospholipids are removed from VLDL by two pathways: hydrolysis of glycerophospholipids by the heparin-releasable phospholipase activity (greater than50%) and transfer to high density lipoproteins (less than50%). The tissue origin of the postheparin phospholipase was studied in plasma obtained from intact rats and supradiaphragmatic rats using specific inhibitors of the extrahepatic lipase system (protamine sulfate and 0.5 M NaCl). The phospholipase activity could be ascribed to both the hepatic and extrahepatic lipase systems. It is concluded that hydrolysis of glycerophospholipids is the major mechanism responsible for the removal of phospholipids from very low density lipoprotein during the degradation of the lipoprotein. It is suggested that phospholipid hydrolysis occurs concomitantly with triglyceride hydrolysis, predominantly in extrahepatic tissues."}
{"id": "PMID:186549", "title": "Effect of epinephrine on the oxidative desaturation of fatty acids in the rat.", "content": "The effect of epinephrine on the oxidative desaturation of fatty acids by liver microsomal preparations of rats has been studied. Administration of epinephrine (1 mg/kg body weight) produced a significant decrease in desaturation of [l-14C]=linoleic acid to gamma-linolenic acid and of [L-14C]alpha-linolenic acid to actadeca-6,9,12,15-tetraenoic acid 12 hr after the infection. Lower doses produced a lesser effect on the delta6-desaturation activity. Epinephrine administration modified the V max of linoleic acid desaturation but not the K m. There was also a slight increase in palmityl desaturation activity. The effect of epinephrine on delta6-desaturation activity was postulated to be mediated through an enhancement of the intracellular cyclic AMP levels that lead to an increase of a glucose metabolite. This metabolite would inhibit delta6-desaturation activity.", "contents": "Effect of epinephrine on the oxidative desaturation of fatty acids in the rat. The effect of epinephrine on the oxidative desaturation of fatty acids by liver microsomal preparations of rats has been studied. Administration of epinephrine (1 mg/kg body weight) produced a significant decrease in desaturation of [l-14C]=linoleic acid to gamma-linolenic acid and of [L-14C]alpha-linolenic acid to actadeca-6,9,12,15-tetraenoic acid 12 hr after the infection. Lower doses produced a lesser effect on the delta6-desaturation activity. Epinephrine administration modified the V max of linoleic acid desaturation but not the K m. There was also a slight increase in palmityl desaturation activity. The effect of epinephrine on delta6-desaturation activity was postulated to be mediated through an enhancement of the intracellular cyclic AMP levels that lead to an increase of a glucose metabolite. This metabolite would inhibit delta6-desaturation activity."}
{"id": "PMID:186550", "title": "Aliphatic medium chain tricarboxylic acids in rat urine.", "content": "Three aliphatic tricarboxylic acids have been found in rat urine. They have been identified as 6-carboxy-5-undecenedioic acid, 6-carboxy-5-dodecenedoic acid, and 6-carboxy-5-tridecenedioic acid. The carbon skeleton structure was determined by mass spectra of the hydrogenated methyl esters. The double bond position was determined after osmium tetroxide oxidation followed by trifluoroacetylation and mass spectrometry and by infrared spectrometry. The compounds were present in the urine when the rats were fed on pellets but disappeared when they received sucrose and water. The acids were not present in the pellets, and a metabolic relation to compounds of longer chain length, possibly mycolic acids, is likely.", "contents": "Aliphatic medium chain tricarboxylic acids in rat urine. Three aliphatic tricarboxylic acids have been found in rat urine. They have been identified as 6-carboxy-5-undecenedioic acid, 6-carboxy-5-dodecenedoic acid, and 6-carboxy-5-tridecenedioic acid. The carbon skeleton structure was determined by mass spectra of the hydrogenated methyl esters. The double bond position was determined after osmium tetroxide oxidation followed by trifluoroacetylation and mass spectrometry and by infrared spectrometry. The compounds were present in the urine when the rats were fed on pellets but disappeared when they received sucrose and water. The acids were not present in the pellets, and a metabolic relation to compounds of longer chain length, possibly mycolic acids, is likely."}
{"id": "PMID:186551", "title": "Effects of free fatty acids on the enzymic synthesis of diacyl and ether types of choline and ethanolamine phosphoglycerides.", "content": "Activities of ethanolaminephosphotransferases (EC 2.7.8.1) and choline phosphotransferases (EC 2.7.8.2) in microsomal fractions from brains and livers of mature rats are increased several fold by the addition of 1,2-diacyl-sn-glycerols or 1-alkyl-2-acyl-sn-clycerols. Oleic acid added with diacylglycerols stimulated further the synthesis of lecithins by liver microsomes, confirming the work of Sribney and Lyman (Can J. Biochem. 51: 1479-1486, 1973). With alkylacylglycerols, oleic and stearic acids were inhibitory and linoleic acid was even more inhibitory for the synthesis of both 1-alkyl-1-acyl-sn-glycero-3-phosphorylcholines and the corresponding ethanolamine compounds with microsomes from both tissues. Free fatty acids without added diglycerides had mixed effects. These results are best explained by postulating the presence of two isoenzymes each for ethanolaminephosphotransferase and cholinephosphotransferase of which only one is affected by free fatty acids. Regulation of the phosphotransferases by free fatty acids may determine the proportion of CDP-choline and CDP-ethanolamine used for synthesis of diacyl and alkylacyl types of these phosphoglycerides.", "contents": "Effects of free fatty acids on the enzymic synthesis of diacyl and ether types of choline and ethanolamine phosphoglycerides. Activities of ethanolaminephosphotransferases (EC 2.7.8.1) and choline phosphotransferases (EC 2.7.8.2) in microsomal fractions from brains and livers of mature rats are increased several fold by the addition of 1,2-diacyl-sn-glycerols or 1-alkyl-2-acyl-sn-clycerols. Oleic acid added with diacylglycerols stimulated further the synthesis of lecithins by liver microsomes, confirming the work of Sribney and Lyman (Can J. Biochem. 51: 1479-1486, 1973). With alkylacylglycerols, oleic and stearic acids were inhibitory and linoleic acid was even more inhibitory for the synthesis of both 1-alkyl-1-acyl-sn-glycero-3-phosphorylcholines and the corresponding ethanolamine compounds with microsomes from both tissues. Free fatty acids without added diglycerides had mixed effects. These results are best explained by postulating the presence of two isoenzymes each for ethanolaminephosphotransferase and cholinephosphotransferase of which only one is affected by free fatty acids. Regulation of the phosphotransferases by free fatty acids may determine the proportion of CDP-choline and CDP-ethanolamine used for synthesis of diacyl and alkylacyl types of these phosphoglycerides."}
{"id": "PMID:186553", "title": "Antibodies in human sera to oncorna virus-like proteins from normal or leukemia marrow cell cultures.", "content": "Some human marrows in culture release particles with oncornavirus-like properties. This study was designed to examine the immunological properties of similar particles in human marrow culture supernates. Leukemic and nonleukemic marrows were cultured for 5-7 days in the presence of [14C]uridine and [3H]leucine or [3H]glucosamine. Labeled supernatant components banding in sucrose gradient densities of 1.20-1.24 g/ml were used as antigen in a double antibody immunoprecipitation assay. The assay was validated by end point titrations and competition with unlabeled antigen; purified myeloma proteins were used as negative controls. Cross-reactivity with mammalian oncornaviruses, as judged by competitive inhibition of precipitation by these viruses, was slight and at the border of the sensitivity of the method. Precipitated antigens analyzed by SDS polyacrylamide gel electrophoresis contained three distinct polypeptides of about 70,000, 45,000 and 30,000 mol wt; these comigrated with the gp 70, pg 45, and p 30 of a murine leukemia virus. Similar polypeptides were obtained from both leukemic and nonleukemic marrow culture supernates. As determined by the radioimmunoprecipitation assay, 32 of 45 leukemic sera (71%), 36 of 45 normal sera (80%), 15 of 19 sera from family contacts of leukemic patients (79%), 14 of 21 cord blood specimens (67%), and 21 of 23 sera (91%) from patients with systemic lupus erythematosus had detectable antibody activity.", "contents": "Antibodies in human sera to oncorna virus-like proteins from normal or leukemia marrow cell cultures. Some human marrows in culture release particles with oncornavirus-like properties. This study was designed to examine the immunological properties of similar particles in human marrow culture supernates. Leukemic and nonleukemic marrows were cultured for 5-7 days in the presence of [14C]uridine and [3H]leucine or [3H]glucosamine. Labeled supernatant components banding in sucrose gradient densities of 1.20-1.24 g/ml were used as antigen in a double antibody immunoprecipitation assay. The assay was validated by end point titrations and competition with unlabeled antigen; purified myeloma proteins were used as negative controls. Cross-reactivity with mammalian oncornaviruses, as judged by competitive inhibition of precipitation by these viruses, was slight and at the border of the sensitivity of the method. Precipitated antigens analyzed by SDS polyacrylamide gel electrophoresis contained three distinct polypeptides of about 70,000, 45,000 and 30,000 mol wt; these comigrated with the gp 70, pg 45, and p 30 of a murine leukemia virus. Similar polypeptides were obtained from both leukemic and nonleukemic marrow culture supernates. As determined by the radioimmunoprecipitation assay, 32 of 45 leukemic sera (71%), 36 of 45 normal sera (80%), 15 of 19 sera from family contacts of leukemic patients (79%), 14 of 21 cord blood specimens (67%), and 21 of 23 sera (91%) from patients with systemic lupus erythematosus had detectable antibody activity."}
{"id": "PMID:186554", "title": "Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection.", "content": "The role of interferon in the pathogenesis of encephalomyocarditis (EMC) virus infection was determined by treating mice with potent, partially purified sheep anti-mouse interferon globulin. In control mice, EMC virus was present in low titers in various visceral organs but attained high titers in the brain towards the 4th to 5th day, at which time mice died with signs of central nervous system disease. In mice treated with anti-mouse interferon globulin, virus was present in high titer in visceral organs 24--36 h after viral inoculation and virtually all mice were dead by 45 h. This rapid evolution of EMC virus infection was not observed in mice treated with the globulin fraction prepared from a normal sheep, from a sheep exhibiting a low anti-mouse interferon-neutralizing titer, nor from a sheep having a high titer of antibody to human leukocyte interferon. The experimental results indicated that anti-interferon globulin neutralized the interferon liberated by virus-infected cells, thus permitting extensive virus multiplication in several visceral organs. We conclude that interferon is an important early component of host resistance to this virus infection.", "contents": "Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection. The role of interferon in the pathogenesis of encephalomyocarditis (EMC) virus infection was determined by treating mice with potent, partially purified sheep anti-mouse interferon globulin. In control mice, EMC virus was present in low titers in various visceral organs but attained high titers in the brain towards the 4th to 5th day, at which time mice died with signs of central nervous system disease. In mice treated with anti-mouse interferon globulin, virus was present in high titer in visceral organs 24--36 h after viral inoculation and virtually all mice were dead by 45 h. This rapid evolution of EMC virus infection was not observed in mice treated with the globulin fraction prepared from a normal sheep, from a sheep exhibiting a low anti-mouse interferon-neutralizing titer, nor from a sheep having a high titer of antibody to human leukocyte interferon. The experimental results indicated that anti-interferon globulin neutralized the interferon liberated by virus-infected cells, thus permitting extensive virus multiplication in several visceral organs. We conclude that interferon is an important early component of host resistance to this virus infection."}
{"id": "PMID:186555", "title": "Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. II. Studies with herpes simplex, Moloney sarcoma, vesicular stomatitis, Newcastle disease, and influenza viruses.", "content": "The effect of potent sheep anti-mouse interferon globulin was investigated in several different experimental virus diseases of mice. In anti-interferon globulin-treated mice infected intraperitoneally with herpes simplex virus (HSV) type I, the latent period was shortened, and the overall LD50 was increased several hundredfold compared to virus-infected control mice. When HSV was inoculated subcutaneously all anti-interferon globulin-treated mice died, whereas only 5% of virus-infected control mice died. Subsequent treatment with anti-interferon globulin of previously HSV-infected mice did not result in reactivation of HSV. Treatment of adult mice with anti-interferon globulin resulted in an earlier appearance of MSV-induced tumors, a greater number of mice bearing tumors, an increase in tumor size, and an increase in the duration of tumors. All tumors eventually regressed despite reinjection of anti-interferon globulin. Anti-interferon globulin treatment resulted in a rapid onset of disease and death in adult mice inoculated (intranasal) with VSV and in newborn mice infected with NDV. Anti-interferon globulin exerted no effect on the course of influenza virus infection of mice. We conclude that the early production of interferon is an importane element in the response of the mouse to several viruses exhibiting different pathogeneses.", "contents": "Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. II. Studies with herpes simplex, Moloney sarcoma, vesicular stomatitis, Newcastle disease, and influenza viruses. The effect of potent sheep anti-mouse interferon globulin was investigated in several different experimental virus diseases of mice. In anti-interferon globulin-treated mice infected intraperitoneally with herpes simplex virus (HSV) type I, the latent period was shortened, and the overall LD50 was increased several hundredfold compared to virus-infected control mice. When HSV was inoculated subcutaneously all anti-interferon globulin-treated mice died, whereas only 5% of virus-infected control mice died. Subsequent treatment with anti-interferon globulin of previously HSV-infected mice did not result in reactivation of HSV. Treatment of adult mice with anti-interferon globulin resulted in an earlier appearance of MSV-induced tumors, a greater number of mice bearing tumors, an increase in tumor size, and an increase in the duration of tumors. All tumors eventually regressed despite reinjection of anti-interferon globulin. Anti-interferon globulin treatment resulted in a rapid onset of disease and death in adult mice inoculated (intranasal) with VSV and in newborn mice infected with NDV. Anti-interferon globulin exerted no effect on the course of influenza virus infection of mice. We conclude that the early production of interferon is an importane element in the response of the mouse to several viruses exhibiting different pathogeneses."}
{"id": "PMID:186556", "title": "A morphological and genetic mapping study of bald colony mutants of Streptomyces coelicolor.", "content": "Twelve bld mutations of Streptomyces coelicolor resulting in a lack of visible aerial mycelium were mapped genetically. The mutants were classified into three groups on the basis of colony morphology, production of antibiotics and morphology on different carbon sources. Four map locations were found for the bld genes and three of these were very near the loci of whi genes, which are also involved in differentiation. Closely linked bld mutations had similar phenotypes.", "contents": "A morphological and genetic mapping study of bald colony mutants of Streptomyces coelicolor. Twelve bld mutations of Streptomyces coelicolor resulting in a lack of visible aerial mycelium were mapped genetically. The mutants were classified into three groups on the basis of colony morphology, production of antibiotics and morphology on different carbon sources. Four map locations were found for the bld genes and three of these were very near the loci of whi genes, which are also involved in differentiation. Closely linked bld mutations had similar phenotypes."}
{"id": "PMID:186558", "title": "Preservation of encysted polytomella.", "content": "Cysts of Polytomella parva and Polytomella caeca were recovered after 7 days storage at cryogenic temperatures following drying on shredded filter paper, silica gel or without added substrate. Accelerated storage testing, by exposing dried material to elevated temperatures, indicated that shredded filter paper was the best of the substrates tested. Polytomella parva was recovered after 5 years storage at -30 degrees C when dried on filter paper but not when dried on silic agel. Determinations of the number of cysts recovered indicated that viable cysts survived all conditions of storage tested. However, excystment following storage was delayed, the extent depending on storage conditions and the substrate used for drying. Most rapid recovery occurred when cysts were rehydrated immediately after drying, and after storage on filter paper at below -70 degrees C.", "contents": "Preservation of encysted polytomella. Cysts of Polytomella parva and Polytomella caeca were recovered after 7 days storage at cryogenic temperatures following drying on shredded filter paper, silica gel or without added substrate. Accelerated storage testing, by exposing dried material to elevated temperatures, indicated that shredded filter paper was the best of the substrates tested. Polytomella parva was recovered after 5 years storage at -30 degrees C when dried on filter paper but not when dried on silic agel. Determinations of the number of cysts recovered indicated that viable cysts survived all conditions of storage tested. However, excystment following storage was delayed, the extent depending on storage conditions and the substrate used for drying. Most rapid recovery occurred when cysts were rehydrated immediately after drying, and after storage on filter paper at below -70 degrees C."}
{"id": "PMID:186559", "title": "Long-term persistent vesicular stomatitis virus and rabies virus infection of cells in vitro.", "content": "BHK 21 carrier cells persistently infected with VSV Indiana for over 2 years have been shedding generally very low levels of mature infectious virus or mature T particles (averaging less than one-hundredth p.f.u./cell/day) yet most cells are producing virus antigens and are resistant to homologous superinfection. However, large amounts of biologically active T particle RNP can be recovered from cytoplasmic extracts of these carrier cells even at times when they are shedding no detectable infectious virus. This recovered cytoplasmic RNP replicates (with helper B virions) to produce mature T particles, interferes strongly after DEAE dextran-facilitated uptake and, together with B virions, allows the establishment of a persistent carrier state in exposed cells. No 'provirus' DNA copies of the VSV RNA genome are detectable (less than 1/40 copy/cell or I copy per 40 cells) in carrier cells after more than 2 years of persistent infection, and all transfection attempts have failed using DNA from these VSV carriers or DNA from carrier cells persistently infected with some other negative strand RNA viruses (measles, mumps, LCM, influenza, rabies). Infectious viruses shed after more than I year from carrier cells originally infected with wild-type B virions are small plaque mutants showing a slight temperature sensitivity. Cured cell populations can be obtained from the long term VSV carrier culture by cloning in the presence or absence of antiviral antibody.", "contents": "Long-term persistent vesicular stomatitis virus and rabies virus infection of cells in vitro. BHK 21 carrier cells persistently infected with VSV Indiana for over 2 years have been shedding generally very low levels of mature infectious virus or mature T particles (averaging less than one-hundredth p.f.u./cell/day) yet most cells are producing virus antigens and are resistant to homologous superinfection. However, large amounts of biologically active T particle RNP can be recovered from cytoplasmic extracts of these carrier cells even at times when they are shedding no detectable infectious virus. This recovered cytoplasmic RNP replicates (with helper B virions) to produce mature T particles, interferes strongly after DEAE dextran-facilitated uptake and, together with B virions, allows the establishment of a persistent carrier state in exposed cells. No 'provirus' DNA copies of the VSV RNA genome are detectable (less than 1/40 copy/cell or I copy per 40 cells) in carrier cells after more than 2 years of persistent infection, and all transfection attempts have failed using DNA from these VSV carriers or DNA from carrier cells persistently infected with some other negative strand RNA viruses (measles, mumps, LCM, influenza, rabies). Infectious viruses shed after more than I year from carrier cells originally infected with wild-type B virions are small plaque mutants showing a slight temperature sensitivity. Cured cell populations can be obtained from the long term VSV carrier culture by cloning in the presence or absence of antiviral antibody."}
{"id": "PMID:186560", "title": "RNA synthesis in BHK 21 cells persistently infected with vesicular stomatitis virus and rabies virus.", "content": "Virus-induced RNA synthesis was studied in BHK 21 cells persistently infected with vesicular stomatitis virus (VSV) and rabies virus by labelling RNA synthesized in the presence of antinomycin D. During persistent infection the species of messenger RNA synthesized were similar in size and relative proportions to those seen during acute infection, but there were some minor differences. Full-sized B virion RNA was generally not detected during persistent infection, and new species (probably DI virion RNA) appeared.", "contents": "RNA synthesis in BHK 21 cells persistently infected with vesicular stomatitis virus and rabies virus. Virus-induced RNA synthesis was studied in BHK 21 cells persistently infected with vesicular stomatitis virus (VSV) and rabies virus by labelling RNA synthesized in the presence of antinomycin D. During persistent infection the species of messenger RNA synthesized were similar in size and relative proportions to those seen during acute infection, but there were some minor differences. Full-sized B virion RNA was generally not detected during persistent infection, and new species (probably DI virion RNA) appeared."}
{"id": "PMID:186561", "title": "Inhibitory effect of herpes simplex virus type 1 on type 2 virus replication.", "content": "Simultaneous infection with herpes simplex type I and type 2 viruses of chick embryo fibroblasts (CEF), which are only permissive for type 2 virus, or rabbit embryo fibroblasts (REF), which are permissive for both virus types, resulted in a marked reduction of type 2 virus production. This effect was dependent on the m.o.i. of type I, being expressed at a high rather than a low m.o.i. The rate of interference decreased with the prolongation of the interval between infection with type 2 and type I viruses. No evidence suggestive of interferon involvement was obtained. Partial inactivation of type 2 virus by ultraviolet irradiation enhanced the inhibitory effect of type I virus. On the other hand, u.v. irradiation of type I virus resulted in a progressive loss of inhibitory activity. The results of the present experiments suggest that a type I genome function is responsible for the interfering effect, and that an early step in the growth of type 2 virus is sensitive to the particular type I virus product involved.", "contents": "Inhibitory effect of herpes simplex virus type 1 on type 2 virus replication. Simultaneous infection with herpes simplex type I and type 2 viruses of chick embryo fibroblasts (CEF), which are only permissive for type 2 virus, or rabbit embryo fibroblasts (REF), which are permissive for both virus types, resulted in a marked reduction of type 2 virus production. This effect was dependent on the m.o.i. of type I, being expressed at a high rather than a low m.o.i. The rate of interference decreased with the prolongation of the interval between infection with type 2 and type I viruses. No evidence suggestive of interferon involvement was obtained. Partial inactivation of type 2 virus by ultraviolet irradiation enhanced the inhibitory effect of type I virus. On the other hand, u.v. irradiation of type I virus resulted in a progressive loss of inhibitory activity. The results of the present experiments suggest that a type I genome function is responsible for the interfering effect, and that an early step in the growth of type 2 virus is sensitive to the particular type I virus product involved."}
{"id": "PMID:186562", "title": "Enhancement by phytohaemagglutinin of inactivation of herpes simplex virus by concanavalin A.", "content": "Inactivation of herpes simplex virus (HSV) by concanavalin A (Con A) was enhanced by treatment with phytohaemagglutinin (PHA)-P using a two-stage reaction procedure. Treatment with PHA alone failed to inactivate HSV. Enhancement of inactivation was also effective when HSV was exposed to PHA first. Our results suggest that the envelope of HSV contains receptor sites for Con A which are important in the infectious process, as well as receptor sites for PHA which are not critical for infectivity. Direct interaction of Con A with PHA was demonstrated and the reaction was reversed by alpha-methyl-D-glucoside. The data indicate that PHA stabilized the binding of Con A to the virus since reversal of inactivation by alpha-methyl-D-glucoside was minimal following treatment with Con A and PHA. Con A inactivated only enveloped virions and enhancement by PHA was a general phenomenon.", "contents": "Enhancement by phytohaemagglutinin of inactivation of herpes simplex virus by concanavalin A. Inactivation of herpes simplex virus (HSV) by concanavalin A (Con A) was enhanced by treatment with phytohaemagglutinin (PHA)-P using a two-stage reaction procedure. Treatment with PHA alone failed to inactivate HSV. Enhancement of inactivation was also effective when HSV was exposed to PHA first. Our results suggest that the envelope of HSV contains receptor sites for Con A which are important in the infectious process, as well as receptor sites for PHA which are not critical for infectivity. Direct interaction of Con A with PHA was demonstrated and the reaction was reversed by alpha-methyl-D-glucoside. The data indicate that PHA stabilized the binding of Con A to the virus since reversal of inactivation by alpha-methyl-D-glucoside was minimal following treatment with Con A and PHA. Con A inactivated only enveloped virions and enhancement by PHA was a general phenomenon."}
{"id": "PMID:186563", "title": "Pathogenesis of cytomegalovirus infection. Distribution of viral products, immune complexes and autoimmunity during latent murine infection.", "content": "During studies on the mechanisms of virus latency, reactivation and resultant tissue injury in mice infected with murine cytomegalovirus (MCMV) in utero or at birth, we found the occurrence of three distinct pathological groups. In the first group, mice died within 4 weeks of exposure to virus and showed evidence of tissue injury due to MCMV in multiple tissues and organs of the body. The second group consisted of mice which survived the initial infection and was composed of a minority (about 25%) which shed virus (chronically infected). The third group (about 75%) consisted of mice in which shedding of virus could not be detected (latently infected). Study of the latter group indicated that virus was not detected in brain, thymus, liver, kidneys, urine or serum by co-cultivation techniques or by cellular DNA-MCMV DNA hybridization. In contrast, virus could be activated from spleen cells by co-cultivation with allogenic but not syngeneic feeder cells and MCMV-DNA was detected in amounts equivalent to 3 to 4 virus genomes per 100 spleen cells. In both the latently infected and chronically infected mice, in all strains studied evidence of virus-antivirus immune complex deposits in the renal glomeruli occurred. Only one of the six infected strains (C57 Br/cdJ) studied showed manifestations of autoimmune disease with the formation of antibodies to nuclear antigens, DNA and soluble nucleoprotein.", "contents": "Pathogenesis of cytomegalovirus infection. Distribution of viral products, immune complexes and autoimmunity during latent murine infection. During studies on the mechanisms of virus latency, reactivation and resultant tissue injury in mice infected with murine cytomegalovirus (MCMV) in utero or at birth, we found the occurrence of three distinct pathological groups. In the first group, mice died within 4 weeks of exposure to virus and showed evidence of tissue injury due to MCMV in multiple tissues and organs of the body. The second group consisted of mice which survived the initial infection and was composed of a minority (about 25%) which shed virus (chronically infected). The third group (about 75%) consisted of mice in which shedding of virus could not be detected (latently infected). Study of the latter group indicated that virus was not detected in brain, thymus, liver, kidneys, urine or serum by co-cultivation techniques or by cellular DNA-MCMV DNA hybridization. In contrast, virus could be activated from spleen cells by co-cultivation with allogenic but not syngeneic feeder cells and MCMV-DNA was detected in amounts equivalent to 3 to 4 virus genomes per 100 spleen cells. In both the latently infected and chronically infected mice, in all strains studied evidence of virus-antivirus immune complex deposits in the renal glomeruli occurred. Only one of the six infected strains (C57 Br/cdJ) studied showed manifestations of autoimmune disease with the formation of antibodies to nuclear antigens, DNA and soluble nucleoprotein."}
{"id": "PMID:186564", "title": "Homologous interference induced by a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture.", "content": "Homologous interference between a temperature-sensitive small plaque mutant (HVJ-pB) derived from an HVJ (haemagglutinating virus of Japan - the Sendai strain of parainfluenza I virus) carrier culture of BHK cells and the original wild-type virus (HVJ-W) has been investigated. Prior infection of LLCMK2, HeLa, BHK or mouse L cells with HVJ-pB, both at permissive and non-permissive temperatures, for 24 h resulted in a reduced yield of superinfecting HVJ-W, reflecting a smaller number of cells capable of producing the superinfecting virus. However, HVJ-pB did not interfere with the replication of vesicular stomatitis virus, Sindbis virus or Newcastle disease virus. Interference in this system seems to be due to inhibition of the attachment of superinfecting HVJ-W as a result of intracellular mechanisms operating at a late stage in the replication of the interfering virus. There is also blocking or destruction of cellular receptors by extra-cellular particles of the interfering virus. Protein synthesis coded for by the complete virus genome is required to establish and maintain the interference, and treatment with actinomycin D has no effect on the interference phenomenon.", "contents": "Homologous interference induced by a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture. Homologous interference between a temperature-sensitive small plaque mutant (HVJ-pB) derived from an HVJ (haemagglutinating virus of Japan - the Sendai strain of parainfluenza I virus) carrier culture of BHK cells and the original wild-type virus (HVJ-W) has been investigated. Prior infection of LLCMK2, HeLa, BHK or mouse L cells with HVJ-pB, both at permissive and non-permissive temperatures, for 24 h resulted in a reduced yield of superinfecting HVJ-W, reflecting a smaller number of cells capable of producing the superinfecting virus. However, HVJ-pB did not interfere with the replication of vesicular stomatitis virus, Sindbis virus or Newcastle disease virus. Interference in this system seems to be due to inhibition of the attachment of superinfecting HVJ-W as a result of intracellular mechanisms operating at a late stage in the replication of the interfering virus. There is also blocking or destruction of cellular receptors by extra-cellular particles of the interfering virus. Protein synthesis coded for by the complete virus genome is required to establish and maintain the interference, and treatment with actinomycin D has no effect on the interference phenomenon."}
{"id": "PMID:186565", "title": "The tuberous sclerosis syndrome: clinical and EEG studies in 100 children.", "content": "The evolution of the early clinical and EEG features in 100 children who developed the tuberous sclerosis syndrome is discussed with particular emphasis on individual variability of epileptic manifestations, skin changes, and mental defect. There were 61 boys and 39 girls. Seizures of various kinds occurred in 98 and in the first 2 years of life infantile spasms were a prominent feature (69) with a partial overlap of other kind of seizures (75). Mental defect (88) and poorly pigmented areas of the skin (77) were already detectable in the first 1 to 2 years of life, while fibroangioma of the face (adenoma sebaceum) (77) and intracranial calcifications (35) became increasingly apparent after the age of 2 to 4 years. The EEG abnormalities tended to be gross in the first 2 years of life, but their subsequent evolution was towards multifocal alterations and some areas of relatively better preserved rhythmic activity. The evolution of the various skin lesions did not run parallel either with that of the clinically detectable seizures or with the appearance of intracranial calcifications.", "contents": "The tuberous sclerosis syndrome: clinical and EEG studies in 100 children. The evolution of the early clinical and EEG features in 100 children who developed the tuberous sclerosis syndrome is discussed with particular emphasis on individual variability of epileptic manifestations, skin changes, and mental defect. There were 61 boys and 39 girls. Seizures of various kinds occurred in 98 and in the first 2 years of life infantile spasms were a prominent feature (69) with a partial overlap of other kind of seizures (75). Mental defect (88) and poorly pigmented areas of the skin (77) were already detectable in the first 1 to 2 years of life, while fibroangioma of the face (adenoma sebaceum) (77) and intracranial calcifications (35) became increasingly apparent after the age of 2 to 4 years. The EEG abnormalities tended to be gross in the first 2 years of life, but their subsequent evolution was towards multifocal alterations and some areas of relatively better preserved rhythmic activity. The evolution of the various skin lesions did not run parallel either with that of the clinically detectable seizures or with the appearance of intracranial calcifications."}
{"id": "PMID:186568", "title": "Accumulation of 99mTc-diphosphonate in four patients with hepatic neoplasm: case reports.", "content": "The accumulation of bone-seeking radiopharmaceuticals in extraosseous lesions has been reported in patients with myocardial infarctions, cerebral infarctions, and some soft-tissue tumors. While the precise mechanisms involved remain uncertain, the spectrum of abnormalities exhibiting such accumulation increases. In our laboratory, 99mTc-diphosphonate concentrated in four hepatic tumors (one cholangiocarcinoma and three metastases from colon carcinoma). This property of phosphate-related radiopharmaceuticals has not been reported previously. Awareness of the possibility of focal diphosphonate accumulation in the liver should help avoid confusion with right lower rib-cage metastasis or pleural effusion.", "contents": "Accumulation of 99mTc-diphosphonate in four patients with hepatic neoplasm: case reports. The accumulation of bone-seeking radiopharmaceuticals in extraosseous lesions has been reported in patients with myocardial infarctions, cerebral infarctions, and some soft-tissue tumors. While the precise mechanisms involved remain uncertain, the spectrum of abnormalities exhibiting such accumulation increases. In our laboratory, 99mTc-diphosphonate concentrated in four hepatic tumors (one cholangiocarcinoma and three metastases from colon carcinoma). This property of phosphate-related radiopharmaceuticals has not been reported previously. Awareness of the possibility of focal diphosphonate accumulation in the liver should help avoid confusion with right lower rib-cage metastasis or pleural effusion."}
{"id": "PMID:186569", "title": "Delineation of peripheral bone infarcts in a child with a rare hemoglobinopathy (SOArab) and purpura fulminans: case report.", "content": "A 27-month-old patient with SOArab hemoglobinopathy complicated by purpura fulminants was studied with 99mTc-pyrophosphate. The study showed an absence of radiotracer in the bones of both feet and the distal portions of both hands, along with an increased concentration of radiotracer proximal to the regions of absent radiotracer. Subsequent amputation of the distal portions of all four extremities was necessary because of dry gangrene. The amputation site in each extremity (selected on clinical grounds only) corresponded closely to the junction of absent and increased bone radiotracer, suggesting that bone imaging may be used as an aid in determining the extent of nonviable tissue in similar patients.", "contents": "Delineation of peripheral bone infarcts in a child with a rare hemoglobinopathy (SOArab) and purpura fulminans: case report. A 27-month-old patient with SOArab hemoglobinopathy complicated by purpura fulminants was studied with 99mTc-pyrophosphate. The study showed an absence of radiotracer in the bones of both feet and the distal portions of both hands, along with an increased concentration of radiotracer proximal to the regions of absent radiotracer. Subsequent amputation of the distal portions of all four extremities was necessary because of dry gangrene. The amputation site in each extremity (selected on clinical grounds only) corresponded closely to the junction of absent and increased bone radiotracer, suggesting that bone imaging may be used as an aid in determining the extent of nonviable tissue in similar patients."}
{"id": "PMID:186566", "title": "Infection and disease induced in chimpanzees with 6/94, a parainfluenza type 1 virus isolated from human multiple sclerosis brain.", "content": "A parainfluenza type 1 virus (6/94) recovered from brain cell cultures of two patients with multiple sclerosis (MS) was inoculated into newborn chimpanzees by the intranasal (IN) or intracerebral (IC) routes. Four of the five animals receiving the virus IN developed clinical signs ranging from mild fever, with or without rhinorrhea, to severe respiratory disease. Two of the chimpanzees died as a result of pneumonia. Virus could be recovered from respiratory tracts for as long as 9 days after exposure and was followed by development of specific neutralizing antibody to the 6/94 virus but not to the HA2 strain of parainfluenza type 1. Brain examination showed astrocytosis, especially of posterior fossa structures, activation of microgliacytes and, in one animal, round cell infiltration of leptomeninges. Of thse three animals receiving virus IC, two developed recurrent seizures beginning 14 months after inoculation. One of these was sacrificed at 23 months of age after progressive neurologic disease, with electroencephalographic abnormalities, developed. The third animal died at 3 months of age of intercurrent pneumonia. No virus was recovered from these animals, although all showed antibody conversion to 6/94 but not HA2 virus. A variety of pathologic lesions were seen in the brains of both animals coming to necropsy particularly in the sacrificed chimpanzee. These included subacute encephalitis, extensive cortical and subcortical degeneration, vascular sclerosis, white matter gliosis and axonal dystrophy.", "contents": "Infection and disease induced in chimpanzees with 6/94, a parainfluenza type 1 virus isolated from human multiple sclerosis brain. A parainfluenza type 1 virus (6/94) recovered from brain cell cultures of two patients with multiple sclerosis (MS) was inoculated into newborn chimpanzees by the intranasal (IN) or intracerebral (IC) routes. Four of the five animals receiving the virus IN developed clinical signs ranging from mild fever, with or without rhinorrhea, to severe respiratory disease. Two of the chimpanzees died as a result of pneumonia. Virus could be recovered from respiratory tracts for as long as 9 days after exposure and was followed by development of specific neutralizing antibody to the 6/94 virus but not to the HA2 strain of parainfluenza type 1. Brain examination showed astrocytosis, especially of posterior fossa structures, activation of microgliacytes and, in one animal, round cell infiltration of leptomeninges. Of thse three animals receiving virus IC, two developed recurrent seizures beginning 14 months after inoculation. One of these was sacrificed at 23 months of age after progressive neurologic disease, with electroencephalographic abnormalities, developed. The third animal died at 3 months of age of intercurrent pneumonia. No virus was recovered from these animals, although all showed antibody conversion to 6/94 but not HA2 virus. A variety of pathologic lesions were seen in the brains of both animals coming to necropsy particularly in the sacrificed chimpanzee. These included subacute encephalitis, extensive cortical and subcortical degeneration, vascular sclerosis, white matter gliosis and axonal dystrophy."}
{"id": "PMID:186567", "title": "Immunization of rabbits with secific components of postsynaptic membrane. Acetylcholinesterase and cholinergic receptor.", "content": "Rabbits were immunized versus either an acetylcholinesterase- or a cholinergic receptor-rich fraction isolated from the electric organ of Torpedo marmorata. In both groups of animals we obtained a production of specific antibodies detected by immunodiffusion without cross reaction for the two antigens. Only rabbits immunized with the receptor-rich fraction developed a progressive flaccid paralysis, which affected first the leg muscles, progressively the neck muscles and eventually the respiratory muscles. The paralysis lasted in several animals up to 20 days. Eserine reversed the paralysis only in the first days but was ineffective in the \"chronic\" stage of the disease. In these animals high frequency stimulation of sciatic nerve induced a rapid failure of the responses of the anterior tibialis muscle while the muscle responded normally to a direct stimulation. A period of rest allowed a complete recovery of the muscle from fatigue. Tetani did not evoke the post-tetanic potentiation. Abnormalities, such as lymphocytic infiltration, fibers atrophy and necrosis, smearing and widening of Z line were sometimes present in muscles of Cho-R-immunized rabbits. In ACh-E immunized animals the neuromuscular transmission and the muscle morphology were similar to that of normal animals. Glycogen, ATP, cytochrome C oxidase, phosphorylases and acetylcholinesterase did not change significantly in the muscles of the immunized animals, while a large increase of cholineacetyltransferase activity was present. Red blood cell acetylcholinesterase showed a particularly high activity in ACh-E-immunized animals. The autoimmune paralysis induced in Cho-R-immunized rabbits may be a useful experimental model for further studies on human myasthenia gravis.", "contents": "Immunization of rabbits with secific components of postsynaptic membrane. Acetylcholinesterase and cholinergic receptor. Rabbits were immunized versus either an acetylcholinesterase- or a cholinergic receptor-rich fraction isolated from the electric organ of Torpedo marmorata. In both groups of animals we obtained a production of specific antibodies detected by immunodiffusion without cross reaction for the two antigens. Only rabbits immunized with the receptor-rich fraction developed a progressive flaccid paralysis, which affected first the leg muscles, progressively the neck muscles and eventually the respiratory muscles. The paralysis lasted in several animals up to 20 days. Eserine reversed the paralysis only in the first days but was ineffective in the \"chronic\" stage of the disease. In these animals high frequency stimulation of sciatic nerve induced a rapid failure of the responses of the anterior tibialis muscle while the muscle responded normally to a direct stimulation. A period of rest allowed a complete recovery of the muscle from fatigue. Tetani did not evoke the post-tetanic potentiation. Abnormalities, such as lymphocytic infiltration, fibers atrophy and necrosis, smearing and widening of Z line were sometimes present in muscles of Cho-R-immunized rabbits. In ACh-E immunized animals the neuromuscular transmission and the muscle morphology were similar to that of normal animals. Glycogen, ATP, cytochrome C oxidase, phosphorylases and acetylcholinesterase did not change significantly in the muscles of the immunized animals, while a large increase of cholineacetyltransferase activity was present. Red blood cell acetylcholinesterase showed a particularly high activity in ACh-E-immunized animals. The autoimmune paralysis induced in Cho-R-immunized rabbits may be a useful experimental model for further studies on human myasthenia gravis."}
{"id": "PMID:186572", "title": "Effect of antibiotics on growth of the immature rat.", "content": "The purpose of this study was to quantify the growth promoting effect of a mixture of antibiotics for rats eating diets deficient in protein or an essential amino acid. Male albino weanling rats (70 to 80 g weight, 4 weeks old) were fed (a) a control diet containing all other required nutrients and varying amounts of casein (0 to 27%), or (b) a purified amino acid diet containing all other required nutrients and varying amounts of valine (0 to 70 mumoles/g diet), threonine (0 to 69 mumoles/g diet) or tryptophan (0 to 8.6 mumoles/g diet), with and without an oral antibiotic supplement consisting of neomycin sulfate (10 mg/100 g body weight/day), bacitracin (500 units/100 g body weight/day), and polymyxin B sulfate (1 mg/100 g body weight/day). At suboptimal intake of casein, valine, tryptophan or threonine, rats eating antibiotic-enriched diet showed up to 3 times greater daily body weight gain (deltaBW) than rats eating a similar diet without antibiotics. The growth-promoting effect of antibiotics can be expressed as percent sparing of specified nutrient (casein or individual amino acid), defined as below: (see journal) where nutrient intakeO ab or nutrient intakeab represents that intake of casein or of a particular amino acid which is required to produce a specific deltaBW in antibiotic-free or antibiotic-supplemented group, respectively. The percent sparing was inversely proportional to the dietary content of casein or limiting amino acid. For diets containing 10% to 25%, 25% to 50%, 50% to 75%, and 75% to 100% of the daily requirement of the limiting nitrogenous nutrient, sparing on the average was greater than 80%, 60%, 20%, and less than 10%, respectively. Data on daily food intake of ad libitum fed rats, and data from an experiment with tube-fed rats, showed that the growth-enhancing effect of antibiotics was independent of changes in food intake.", "contents": "Effect of antibiotics on growth of the immature rat. The purpose of this study was to quantify the growth promoting effect of a mixture of antibiotics for rats eating diets deficient in protein or an essential amino acid. Male albino weanling rats (70 to 80 g weight, 4 weeks old) were fed (a) a control diet containing all other required nutrients and varying amounts of casein (0 to 27%), or (b) a purified amino acid diet containing all other required nutrients and varying amounts of valine (0 to 70 mumoles/g diet), threonine (0 to 69 mumoles/g diet) or tryptophan (0 to 8.6 mumoles/g diet), with and without an oral antibiotic supplement consisting of neomycin sulfate (10 mg/100 g body weight/day), bacitracin (500 units/100 g body weight/day), and polymyxin B sulfate (1 mg/100 g body weight/day). At suboptimal intake of casein, valine, tryptophan or threonine, rats eating antibiotic-enriched diet showed up to 3 times greater daily body weight gain (deltaBW) than rats eating a similar diet without antibiotics. The growth-promoting effect of antibiotics can be expressed as percent sparing of specified nutrient (casein or individual amino acid), defined as below: (see journal) where nutrient intakeO ab or nutrient intakeab represents that intake of casein or of a particular amino acid which is required to produce a specific deltaBW in antibiotic-free or antibiotic-supplemented group, respectively. The percent sparing was inversely proportional to the dietary content of casein or limiting amino acid. For diets containing 10% to 25%, 25% to 50%, 50% to 75%, and 75% to 100% of the daily requirement of the limiting nitrogenous nutrient, sparing on the average was greater than 80%, 60%, 20%, and less than 10%, respectively. Data on daily food intake of ad libitum fed rats, and data from an experiment with tube-fed rats, showed that the growth-enhancing effect of antibiotics was independent of changes in food intake."}
{"id": "PMID:186573", "title": "Serum lipid and lipoprotein responses of six nonhuman primate species to dietary changes in cholesterol levels.", "content": "The response of serum lipids and lipoproteins to different levels of cholesterol in the diet was studied in chimpanzee (Pan troglodytes), rhesus (Macaca mulatta), green (Cercopithecus aethiops), patas (Erythrocebus patas), squirrel (Saimiri sciurea) and spider (Ateles sp.) monkeys. Five animals of each species were fed increasing amounts of dietary cholesterol (0.05% to 1.5% W/W) for 3-week periods; between each experimental diet, the animals were fed a basal diet without cholesterol for a similar period. Serum cholesterol response of different species measured in terms of response index (area under the time-concentration curve above basal value) varied with the dietary cholesterol content and showed a significant interspecies difference at 0.5% dietary cholesterol (1.8 mg/kcal) level. The overall response for the different diets allowed ranking of the species as follows: squirrel greater than green greater than spider approximately equal to rhesus approximately equal to patas greater than chimpanzee. The serum lipoprotein response was reflected not only in an increase in beta-lipoprotein but also in alpha-liprotein with significant differences among species in the amount of cholesterol transported in the lipoprotein classes. Challenging the animals with dietary cholesterol seems to be an essential step for determining inter- and intraspecies differences.", "contents": "Serum lipid and lipoprotein responses of six nonhuman primate species to dietary changes in cholesterol levels. The response of serum lipids and lipoproteins to different levels of cholesterol in the diet was studied in chimpanzee (Pan troglodytes), rhesus (Macaca mulatta), green (Cercopithecus aethiops), patas (Erythrocebus patas), squirrel (Saimiri sciurea) and spider (Ateles sp.) monkeys. Five animals of each species were fed increasing amounts of dietary cholesterol (0.05% to 1.5% W/W) for 3-week periods; between each experimental diet, the animals were fed a basal diet without cholesterol for a similar period. Serum cholesterol response of different species measured in terms of response index (area under the time-concentration curve above basal value) varied with the dietary cholesterol content and showed a significant interspecies difference at 0.5% dietary cholesterol (1.8 mg/kcal) level. The overall response for the different diets allowed ranking of the species as follows: squirrel greater than green greater than spider approximately equal to rhesus approximately equal to patas greater than chimpanzee. The serum lipoprotein response was reflected not only in an increase in beta-lipoprotein but also in alpha-liprotein with significant differences among species in the amount of cholesterol transported in the lipoprotein classes. Challenging the animals with dietary cholesterol seems to be an essential step for determining inter- and intraspecies differences."}
{"id": "PMID:186580", "title": "Differentiation of mouse neuroblastoma cells in vitro and in vivo induced by cyclic adenosine monophosphate (cAMP).", "content": "The murine neuroblastoma appears to be a useful model for elucidating the mechanism of cellular differentiation. In tissue culture, MNB cells were induced to \"irreversibly\" differentiate into neuronal-like cells by DBcAMP alone or in combination with cAMP phosphodiesterase inhibitors: papaverine (Pap) and theophylline (Theo). Cells differentiated by DBcAMP, Pap, and Theo were no longer tumorgenic when reinoculated into animals of the host strain. In vivo, DBcAMP, Pap, and Theo caused a reduced tumor volume growth rate in animals with established tumors. Morphologically, this effect appears to be secondary to an arrest of cellular mitoses. Cells insensitive to these agents emerged after 3 to 4 days, and tumor growth accelerated to parallel the rate of the untreated tumors.", "contents": "Differentiation of mouse neuroblastoma cells in vitro and in vivo induced by cyclic adenosine monophosphate (cAMP). The murine neuroblastoma appears to be a useful model for elucidating the mechanism of cellular differentiation. In tissue culture, MNB cells were induced to \"irreversibly\" differentiate into neuronal-like cells by DBcAMP alone or in combination with cAMP phosphodiesterase inhibitors: papaverine (Pap) and theophylline (Theo). Cells differentiated by DBcAMP, Pap, and Theo were no longer tumorgenic when reinoculated into animals of the host strain. In vivo, DBcAMP, Pap, and Theo caused a reduced tumor volume growth rate in animals with established tumors. Morphologically, this effect appears to be secondary to an arrest of cellular mitoses. Cells insensitive to these agents emerged after 3 to 4 days, and tumor growth accelerated to parallel the rate of the untreated tumors."}
{"id": "PMID:186584", "title": "Effects of cyclic nucleotides on mammalian motor nerve terminals.", "content": "This research examined the effects of several cyclic nucleotides on in vivo cat soleus nerves and muscles. The reagents were administered by rapid close intra-arterial injection while electrical activity in single motor axons and contractile activity in the whole muscle were monitored. Cyclic N6-2'-O-dibutyryl adenosine 3',5'-monophosphate (dibutyryl cAMP) initiated bursts of action potentials in unstimulated axons. It also caused the occurrence of stimulus bound repetitive potentials in stimulated axons. It caused the muscle to undergo a series of rapid asynchronous contractions and potentiated the strength of stimulus-evoked contractions. Monobutyryl cAMP produced similar responses, but was less potent than dibutyryl cAMP. cAMP produced only a small, transient depression of neuromuscular transmission. There was no response to dibutyryl cyclic 3',5' guanosine monophosphate or sodium butyrate. None of these reagents affected denervated muscle. The results suggest that cAMP-like materials that can penetrate nerve membranes cause depolarization of motor nerve terminals, prolongation of the depolarization of the terminal initiated by an action potential and release of transmitter.", "contents": "Effects of cyclic nucleotides on mammalian motor nerve terminals. This research examined the effects of several cyclic nucleotides on in vivo cat soleus nerves and muscles. The reagents were administered by rapid close intra-arterial injection while electrical activity in single motor axons and contractile activity in the whole muscle were monitored. Cyclic N6-2'-O-dibutyryl adenosine 3',5'-monophosphate (dibutyryl cAMP) initiated bursts of action potentials in unstimulated axons. It also caused the occurrence of stimulus bound repetitive potentials in stimulated axons. It caused the muscle to undergo a series of rapid asynchronous contractions and potentiated the strength of stimulus-evoked contractions. Monobutyryl cAMP produced similar responses, but was less potent than dibutyryl cAMP. cAMP produced only a small, transient depression of neuromuscular transmission. There was no response to dibutyryl cyclic 3',5' guanosine monophosphate or sodium butyrate. None of these reagents affected denervated muscle. The results suggest that cAMP-like materials that can penetrate nerve membranes cause depolarization of motor nerve terminals, prolongation of the depolarization of the terminal initiated by an action potential and release of transmitter."}
{"id": "PMID:186585", "title": "A role of cyclic nucleotides in neuromuscular transmission.", "content": "This research explored the possibility that cyclic nucleotides are part of the excitation-secretion sequence in mammalian motor nerve terminals. A series of reagents known to react with the enzymes that synthesize and degrade cyclic nucleotides or that are effectors of cyclic nucleotide actions were administered to in vivo cat soleus nerve-muscle preparations. The reagents were administered by rapid close intra-arterial injection while electrical activity in single motor axons and contractile activity of the muscle were monitored. NaF, an activator of adenylate cyclase, evoked bursts of action potentials in unstimulated axons and caused stimulus-bound repetitive activity in stimulated axons. It evoked vigorous asynchronous activity in the muscle and potentiated the force of muscle contraction. These effects are identical with those of cyclic N6-2'-O-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cAMP). Prostaglandin E1 produced similar effects. Dithiobisnitrobenzoic acid and alloxan, inhibitors of adenylate cyclase, impaired neuromuscular transmission and prevented the effects of NaF, but they did not change the responses to dibutyryl cAMP. Theophylline, an inhibitor of phosphodiesterase, caused axons to respond repetitively to stimulation, but this activity had a different pattern from that produced by dibutyryl cAMP or NaF. Pretreatment with theophylline enhanced the responses to dibutyryl cAMP and NaF. Imidazole, an activator of phosphodiesterase, impaired neuromuscular transmission and prevented the effects of dibutyryl cAMP and NaF. Adenosine, an inhibitor of protein kinase, or verapamil, which inhibits calcium flux, impaired neuromuscular transmission and prevented the responses to dibutyryl cAMP, NaF and theophylline. These results are compatible with the hypothesis that cAMP is involved in the regulation of calcium flux and transmitter secretion in mammalian motor nerve terminals.", "contents": "A role of cyclic nucleotides in neuromuscular transmission. This research explored the possibility that cyclic nucleotides are part of the excitation-secretion sequence in mammalian motor nerve terminals. A series of reagents known to react with the enzymes that synthesize and degrade cyclic nucleotides or that are effectors of cyclic nucleotide actions were administered to in vivo cat soleus nerve-muscle preparations. The reagents were administered by rapid close intra-arterial injection while electrical activity in single motor axons and contractile activity of the muscle were monitored. NaF, an activator of adenylate cyclase, evoked bursts of action potentials in unstimulated axons and caused stimulus-bound repetitive activity in stimulated axons. It evoked vigorous asynchronous activity in the muscle and potentiated the force of muscle contraction. These effects are identical with those of cyclic N6-2'-O-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cAMP). Prostaglandin E1 produced similar effects. Dithiobisnitrobenzoic acid and alloxan, inhibitors of adenylate cyclase, impaired neuromuscular transmission and prevented the effects of NaF, but they did not change the responses to dibutyryl cAMP. Theophylline, an inhibitor of phosphodiesterase, caused axons to respond repetitively to stimulation, but this activity had a different pattern from that produced by dibutyryl cAMP or NaF. Pretreatment with theophylline enhanced the responses to dibutyryl cAMP and NaF. Imidazole, an activator of phosphodiesterase, impaired neuromuscular transmission and prevented the effects of dibutyryl cAMP and NaF. Adenosine, an inhibitor of protein kinase, or verapamil, which inhibits calcium flux, impaired neuromuscular transmission and prevented the responses to dibutyryl cAMP, NaF and theophylline. These results are compatible with the hypothesis that cAMP is involved in the regulation of calcium flux and transmitter secretion in mammalian motor nerve terminals."}
{"id": "PMID:186586", "title": "Effects of uridine and inosine on glucose metabolism in skeletal muscle and activated lipolysis in adipose tissue.", "content": "In a first series of experiments, the effects of uridine and inosine on glucose metabolism in rat diaphragm muscle incubated in Krebs-bicarbonate buffer were studied. Uridine in concentrations of 10(-4) to 10(-6) M stimulated the uptake of glucose and  increased the content of glycogen, but had no effect on the production of lactate. When diaphragm muscles were incubated in the buffer without glucose, uridine (10(-4)-10(-6) M) had no effects on the content of glycogen and on the production of lactate. On the other hand, inosine in concentrations of 10(-4) to 10(-6) M stimulated the uptake of glucose and the production of lactate, but had no effect on the content of glycogen in the muscle. In a second series of experiments, uridine (10(-4)-10(-5) M) and inosine (10(-4)-10(-7) M) inhibited the relase of glycerol from isolated rat epididymal adipose tissue in Krebs-bicarbonate buffer. Uridine and inosine in concentrations of 10(-4) M inhibited the epinephrine (10(-5) M)-, the norepinephrine (10(-5) M)- and the theophylline (10(-3) M)-stimulated lipolysis. Dibutyryl 3',5'-adenosine monophosphate-stimulated lipolysis was further activated in the presence of 10(-4) M uridine or inosine. Dose-response curves studies suggested that inosine, but not uridine, has a common receptor site with epinephrine in adipose tissue. These results demonstrated that both nucleosides stimulated the glucose uptake, but only uridine increased the synthesis of glycogen in the muscle. Both nucleosides also inhibited lipolysis in adipose tissue. The mechanism of antilipolytic action of these nucleosides is unknown, but one of the receptor sites for inosine might be adenylate cyclase.", "contents": "Effects of uridine and inosine on glucose metabolism in skeletal muscle and activated lipolysis in adipose tissue. In a first series of experiments, the effects of uridine and inosine on glucose metabolism in rat diaphragm muscle incubated in Krebs-bicarbonate buffer were studied. Uridine in concentrations of 10(-4) to 10(-6) M stimulated the uptake of glucose and  increased the content of glycogen, but had no effect on the production of lactate. When diaphragm muscles were incubated in the buffer without glucose, uridine (10(-4)-10(-6) M) had no effects on the content of glycogen and on the production of lactate. On the other hand, inosine in concentrations of 10(-4) to 10(-6) M stimulated the uptake of glucose and the production of lactate, but had no effect on the content of glycogen in the muscle. In a second series of experiments, uridine (10(-4)-10(-5) M) and inosine (10(-4)-10(-7) M) inhibited the relase of glycerol from isolated rat epididymal adipose tissue in Krebs-bicarbonate buffer. Uridine and inosine in concentrations of 10(-4) M inhibited the epinephrine (10(-5) M)-, the norepinephrine (10(-5) M)- and the theophylline (10(-3) M)-stimulated lipolysis. Dibutyryl 3',5'-adenosine monophosphate-stimulated lipolysis was further activated in the presence of 10(-4) M uridine or inosine. Dose-response curves studies suggested that inosine, but not uridine, has a common receptor site with epinephrine in adipose tissue. These results demonstrated that both nucleosides stimulated the glucose uptake, but only uridine increased the synthesis of glycogen in the muscle. Both nucleosides also inhibited lipolysis in adipose tissue. The mechanism of antilipolytic action of these nucleosides is unknown, but one of the receptor sites for inosine might be adenylate cyclase."}
{"id": "PMID:186587", "title": "L-glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction.", "content": "The possibility that L-glutamate is the excitatory transmitter at the Drosophila larval neuromuscular junction and the ionic basis of its action on the muscle membrane are examined. 2. Iontophoretically applied L-glutamate causes muscle depolarization (L-glutamate potential) if and only if the L-glutamate pipette is within a few mum of the nerve ending. D-glutamate, substance P, ACh and GABA are ineffective. 3. Bath-applied L-glutamate produces similar changes in the time course and amplitude of miniature excitatory junctional potential (m.e.j.p.), excitatory junctional potential (e.j.p.) and the L-glutamate potential. 4. Neuromuscular transmission and excitation-contraction coupling are operative in a haemolymph-like solution containing 1 mM L-glutamate. 5. The reversal potentials of the e.j.p. and the L-glutamate potential are identical to each other, changing similarly with changes in the ionic compositions of the external medium (twelve solutions). 6. The ionic dependence of the reversal potentials is predicted from an extended constant-field equation using a ratio of sodium:potassium permeabilities of PNa/PK=1-3, and a ratio of magnesium:potassium permeabilities of PMg/PK=4-7. 7. It is concluded that L-glutamate is, or is an agonist of, the excitatory transmitter at certain Drosophila larval neuromuscular junctions.", "contents": "L-glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction. The possibility that L-glutamate is the excitatory transmitter at the Drosophila larval neuromuscular junction and the ionic basis of its action on the muscle membrane are examined. 2. Iontophoretically applied L-glutamate causes muscle depolarization (L-glutamate potential) if and only if the L-glutamate pipette is within a few mum of the nerve ending. D-glutamate, substance P, ACh and GABA are ineffective. 3. Bath-applied L-glutamate produces similar changes in the time course and amplitude of miniature excitatory junctional potential (m.e.j.p.), excitatory junctional potential (e.j.p.) and the L-glutamate potential. 4. Neuromuscular transmission and excitation-contraction coupling are operative in a haemolymph-like solution containing 1 mM L-glutamate. 5. The reversal potentials of the e.j.p. and the L-glutamate potential are identical to each other, changing similarly with changes in the ionic compositions of the external medium (twelve solutions). 6. The ionic dependence of the reversal potentials is predicted from an extended constant-field equation using a ratio of sodium:potassium permeabilities of PNa/PK=1-3, and a ratio of magnesium:potassium permeabilities of PMg/PK=4-7. 7. It is concluded that L-glutamate is, or is an agonist of, the excitatory transmitter at certain Drosophila larval neuromuscular junctions."}
{"id": "PMID:186588", "title": "The release of endogenous amino acids from the rat visual cortex.", "content": "The release of endogenous taurine, GABA, glycine, aspartate, glutamate, glutamine and alanine from the rat visual cortex was measured using a cortical cup technique. The electrocorticogram (ECoG) was monitored throughout most experiments. 2. Spreading depression, evoked by the dropwise placement of 10% KCl solution on to the brain outside the cup was associated with a significant increase in the release of GABA and glutamine but a marked fall in that of glutamate. The evoked release of GABA and glutamate but not of glutamine was Ca2+ dependent. 3. A solution containing 50 mM-K+ placed within the cup elicited a significant increase in the release of taurine and GABA, whereas 100 mM-K+ additionally released aspartate and glutamate. The K+-evoked release of these amino acids with the exceptions of taurine and glutamine was Ca2+-dependent. 4. Three series of experiments were carried out in which the preparations were stimulated electrically. Bipolar stimulation (100 Hz, 1 msec pulse width, 2-5 mA for 5 min) with the electrode within the cup was followed by significant increases in taurine, GABA and glutamate release; using a 5 mA current, there was an additional release of aspartate and alanine. Only the evoked release of GABA and glutamate was Ca2+ dependent. 5. In the second and third series of experiments, the electrode was sited adjacent to the cup or on the contralateral cortex respectively. Following stimulation (100 Hz, 1 msec pulse width, 2-5 mA for 5 min) there was a significant increase in taurine and GABA release and a significant fall in the release of aspartate and glutamate. With the exception of taurine, these changes in release were Ca2+ dependent. Reducing the stimulus current to 1-5 mA or the period of stimulation to 2-5 min initiated similar but statistically insignificant changes in release. A range (10-100 Hz) of stimulation frequencies was examined: the evoked release of GABA was linearly related to frequency whereas that of taurine was frequency-independent. The fall in aspartate and glutamate release was maximal at a frequency of about 50 Hz. 6. The results are discussed in relation to (a) the possible sites of release of the amino acids and (b) the proposed neurotransmitter roles of the physiologically active amino acids.", "contents": "The release of endogenous amino acids from the rat visual cortex. The release of endogenous taurine, GABA, glycine, aspartate, glutamate, glutamine and alanine from the rat visual cortex was measured using a cortical cup technique. The electrocorticogram (ECoG) was monitored throughout most experiments. 2. Spreading depression, evoked by the dropwise placement of 10% KCl solution on to the brain outside the cup was associated with a significant increase in the release of GABA and glutamine but a marked fall in that of glutamate. The evoked release of GABA and glutamate but not of glutamine was Ca2+ dependent. 3. A solution containing 50 mM-K+ placed within the cup elicited a significant increase in the release of taurine and GABA, whereas 100 mM-K+ additionally released aspartate and glutamate. The K+-evoked release of these amino acids with the exceptions of taurine and glutamine was Ca2+-dependent. 4. Three series of experiments were carried out in which the preparations were stimulated electrically. Bipolar stimulation (100 Hz, 1 msec pulse width, 2-5 mA for 5 min) with the electrode within the cup was followed by significant increases in taurine, GABA and glutamate release; using a 5 mA current, there was an additional release of aspartate and alanine. Only the evoked release of GABA and glutamate was Ca2+ dependent. 5. In the second and third series of experiments, the electrode was sited adjacent to the cup or on the contralateral cortex respectively. Following stimulation (100 Hz, 1 msec pulse width, 2-5 mA for 5 min) there was a significant increase in taurine and GABA release and a significant fall in the release of aspartate and glutamate. With the exception of taurine, these changes in release were Ca2+ dependent. Reducing the stimulus current to 1-5 mA or the period of stimulation to 2-5 min initiated similar but statistically insignificant changes in release. A range (10-100 Hz) of stimulation frequencies was examined: the evoked release of GABA was linearly related to frequency whereas that of taurine was frequency-independent. The fall in aspartate and glutamate release was maximal at a frequency of about 50 Hz. 6. The results are discussed in relation to (a) the possible sites of release of the amino acids and (b) the proposed neurotransmitter roles of the physiologically active amino acids."}
{"id": "PMID:186589", "title": "Phosphorylation reactions in islets of Langerhans.", "content": "The possible significance of phosphorylation reaction in islets of Langerhans in relation to the secretion of insulin is discussed. The secretagogues, glucose and its metabolites, cAMP and Ca++ and their influences on protein-kinase activity are given particular attention. The data obtained by the authors, as well as by other groups, are in agreement that cAMP is a potent stimulator of protein kinase activity. Glucose and its metabolites influenced protein kinase activity in one instance. Ca++ in supraphysiological amounts inhibited protein phosphorylation. The links between phosphorylation reactions and insulin secretion are, at the present time, conjectural.", "contents": "Phosphorylation reactions in islets of Langerhans. The possible significance of phosphorylation reaction in islets of Langerhans in relation to the secretion of insulin is discussed. The secretagogues, glucose and its metabolites, cAMP and Ca++ and their influences on protein-kinase activity are given particular attention. The data obtained by the authors, as well as by other groups, are in agreement that cAMP is a potent stimulator of protein kinase activity. Glucose and its metabolites influenced protein kinase activity in one instance. Ca++ in supraphysiological amounts inhibited protein phosphorylation. The links between phosphorylation reactions and insulin secretion are, at the present time, conjectural."}
{"id": "PMID:186590", "title": "Studies on the function of pancreatic islet cell membranes.", "content": "Pancreatic islets rich in beta-cells were isolated from non-inbred ob/ob-mice and used for studying various aspects of the function of the plasma membrane. A review is given of the authors' work along the following lines: the role of transmembrane transport or membrane binding in the recognition of insulin-releasing sugars, amino acids, sulfonylureas, and sulphydryl-blocking agents; the role of cyclic 3',5'-AMP and cations in the coupling of stimulus recognition to insulin discharge; alloxan beta-cytotoxicity in vitro and its prevention by sugars; the isolation of a subcellular fraction enriched by plasma membranes. 1. It is suggested that D-glucose is recognized as an insulin secretagogue by being metabolized in the beta-cells; the teleological purpose of the transmembrane transport system being to allow fluctuations of the extracellular glucose concentration to be rapidly transmitted to the cell interior. Insulin-releasing sulfonyluraes and sulphydryl reagents are thought to act directly on the beta-cell plasma membrane, however. 2. Although cyclic 3',5'-AMP may amplify the expression of a secretory signal induced by D-glucose, studies with cholera toxin suggest that activation of the adenylate cyclase does not per se elicit secretion. The increase of islet cyclic 3',5'-AMP observed in response to several secretagogues, including D-glucose, may be secondary to membrane depolarization. 3. The possible role of an electrodiffusional mechanism in controlling the electrical potential is emphasized; a decrease of K+ permeability, rather than an increase of Na+ permeability, is suggested to be involved in the depolarizing action of D-glucose. Studies with the lanthanum-wash technique indicated that D-glucose causes a net flux of Ca2+ from the outside to the inside of the beta-cells. Although this uptake may relate to the enhancement of insulin secretion, the detailed mechanisms are unclear. 4. Inhibition of the Na+/K+ pump may be one of the earliest events in damage to the beta-cell by alloxan, on the basis of Rb+ studies. Protective effects of glucose against alloxan toxicity appear to be close related. 5. Studies of enzyme markers, the binding of wheat germ agglutinin, and electron microscopy indicate the presence of plasma membranes in a smooth-membrane fraction obtained by fractionating islet homogenates at consecutive sucrose gradients.", "contents": "Studies on the function of pancreatic islet cell membranes. Pancreatic islets rich in beta-cells were isolated from non-inbred ob/ob-mice and used for studying various aspects of the function of the plasma membrane. A review is given of the authors' work along the following lines: the role of transmembrane transport or membrane binding in the recognition of insulin-releasing sugars, amino acids, sulfonylureas, and sulphydryl-blocking agents; the role of cyclic 3',5'-AMP and cations in the coupling of stimulus recognition to insulin discharge; alloxan beta-cytotoxicity in vitro and its prevention by sugars; the isolation of a subcellular fraction enriched by plasma membranes. 1. It is suggested that D-glucose is recognized as an insulin secretagogue by being metabolized in the beta-cells; the teleological purpose of the transmembrane transport system being to allow fluctuations of the extracellular glucose concentration to be rapidly transmitted to the cell interior. Insulin-releasing sulfonyluraes and sulphydryl reagents are thought to act directly on the beta-cell plasma membrane, however. 2. Although cyclic 3',5'-AMP may amplify the expression of a secretory signal induced by D-glucose, studies with cholera toxin suggest that activation of the adenylate cyclase does not per se elicit secretion. The increase of islet cyclic 3',5'-AMP observed in response to several secretagogues, including D-glucose, may be secondary to membrane depolarization. 3. The possible role of an electrodiffusional mechanism in controlling the electrical potential is emphasized; a decrease of K+ permeability, rather than an increase of Na+ permeability, is suggested to be involved in the depolarizing action of D-glucose. Studies with the lanthanum-wash technique indicated that D-glucose causes a net flux of Ca2+ from the outside to the inside of the beta-cells. Although this uptake may relate to the enhancement of insulin secretion, the detailed mechanisms are unclear. 4. Inhibition of the Na+/K+ pump may be one of the earliest events in damage to the beta-cell by alloxan, on the basis of Rb+ studies. Protective effects of glucose against alloxan toxicity appear to be close related. 5. Studies of enzyme markers, the binding of wheat germ agglutinin, and electron microscopy indicate the presence of plasma membranes in a smooth-membrane fraction obtained by fractionating islet homogenates at consecutive sucrose gradients."}
{"id": "PMID:186593", "title": "Teen-age alcohol abuse.", "content": "In summary, we have seen that there isn't sufficient data available to properly assess this problem, but from what exists we are fairly sure that teen-age alcohol abuse is on the rise. We have also noted that there are many area agencies for alcoholics, but that there is not much coordinated effort, and essentially none for teen-agers. This is probably due to its being a relatively new trend and that many people are apparently refusing to admit that it exists. Also covered were possible causes for this new problem and the various roles of nurses in prevention. These include school nurses, public health nurses, and others in community and state politics, promotion of new educational methods, family teaching both at home and in the hospital, new responsibilities of the school nurse, and research. These are challenging roles, but also very important considering that these teen-agers who are flirting with trouble today will be rearing families and defining social behavior tomorrow.", "contents": "Teen-age alcohol abuse. In summary, we have seen that there isn't sufficient data available to properly assess this problem, but from what exists we are fairly sure that teen-age alcohol abuse is on the rise. We have also noted that there are many area agencies for alcoholics, but that there is not much coordinated effort, and essentially none for teen-agers. This is probably due to its being a relatively new trend and that many people are apparently refusing to admit that it exists. Also covered were possible causes for this new problem and the various roles of nurses in prevention. These include school nurses, public health nurses, and others in community and state politics, promotion of new educational methods, family teaching both at home and in the hospital, new responsibilities of the school nurse, and research. These are challenging roles, but also very important considering that these teen-agers who are flirting with trouble today will be rearing families and defining social behavior tomorrow."}
{"id": "PMID:186599", "title": "Some barriers to effective alcoholism research.", "content": "Barriers to effective alcoholism research include the search for unitary etiological factors, the difficulties in assembling homogeneous samples of subjects for study, the lack of widespread multidisciplinary efforts, and uncertainty about the goals of treatment for alcoholism. Innovative research approaches are needed for alcoholism prevention in order to preclude the proliferation of patterns of alcohol abuse.", "contents": "Some barriers to effective alcoholism research. Barriers to effective alcoholism research include the search for unitary etiological factors, the difficulties in assembling homogeneous samples of subjects for study, the lack of widespread multidisciplinary efforts, and uncertainty about the goals of treatment for alcoholism. Innovative research approaches are needed for alcoholism prevention in order to preclude the proliferation of patterns of alcohol abuse."}
{"id": "PMID:186600", "title": "[Post-operative radiotherapy of hemisphere gliomas in the adult. A statistical study of 134 cases (author's transl)].", "content": "A series of 134 adults patient with hemisphere gliomas who received post-operative radiation after surgical excision, either by conventional radiotherapy or high energy radiation, between 1966 and 1972 in the L\u00e9on-B\u00e9rard Centre. Overall survival for grade I and II astrocytomas at two years was 15/29, or 51%. Overall survival for glioblastomas was 30/91, i.e. 33% at one year, and 3/91 or 3.3% at two years. High energy radiation gave slightly superior results to conventional radiotherapy. The best results were obtained with concentrated irradiation when two series of irradiation were possible : 8/17 at one year (47%). Analysis of the literature indicates that radiotherapy, whilst remaining controversial for grades I and II astrocytomas, is recognised to be useful by all in the case of glioblastomas. The authors favour the post-operative irradiation 6,00 to 6,500 Rads, localised) for grade I and II astrocytomas with pejorative characteristics and routin- post-operative irradiation for glioblastomas over a wide field taking in almost the entire brain. This may be spread (6,000 Rads) or in a \"split course\" (two series of 1,800 each). The latter technique has the advantage of a simple protocol, better adapted to lesions in which the final prognosis remains very poor. Finally, the indications for radiotherapy in the case of supra-tentorial ependymomas (3 cases) and oligodendrogliomas (6 cases) are presented, together with an analysis of the complications of radiotherapy for cerebral tumours.", "contents": "[Post-operative radiotherapy of hemisphere gliomas in the adult. A statistical study of 134 cases (author's transl)]. A series of 134 adults patient with hemisphere gliomas who received post-operative radiation after surgical excision, either by conventional radiotherapy or high energy radiation, between 1966 and 1972 in the L\u00e9on-B\u00e9rard Centre. Overall survival for grade I and II astrocytomas at two years was 15/29, or 51%. Overall survival for glioblastomas was 30/91, i.e. 33% at one year, and 3/91 or 3.3% at two years. High energy radiation gave slightly superior results to conventional radiotherapy. The best results were obtained with concentrated irradiation when two series of irradiation were possible : 8/17 at one year (47%). Analysis of the literature indicates that radiotherapy, whilst remaining controversial for grades I and II astrocytomas, is recognised to be useful by all in the case of glioblastomas. The authors favour the post-operative irradiation 6,00 to 6,500 Rads, localised) for grade I and II astrocytomas with pejorative characteristics and routin- post-operative irradiation for glioblastomas over a wide field taking in almost the entire brain. This may be spread (6,000 Rads) or in a \"split course\" (two series of 1,800 each). The latter technique has the advantage of a simple protocol, better adapted to lesions in which the final prognosis remains very poor. Finally, the indications for radiotherapy in the case of supra-tentorial ependymomas (3 cases) and oligodendrogliomas (6 cases) are presented, together with an analysis of the complications of radiotherapy for cerebral tumours."}
{"id": "PMID:186601", "title": "[A quantitative and quanlitative examination of bone metastases by whole body scanning with 99mTc-pyrophosphate (author's transl)].", "content": "The purpose of the present work is to \"quantify\" bone scanning, in order to calculate indices of localized uptake that will make it possible to differentiate between normal and pathological uptake, and approach an etiologicial diagnosis. The authors use an Elscint dual head whole body scanner and an offline video display calculator. The patient is given 8 mc technetium 99m pyrophosphate 4 hours prior to scanning. The whole body count is expressed in thousands of counts multipled by two so that the knee to whole body ratio is close to one, to facilitate comparison of the indices. Results show that the presence of metastases is demonstrated more clearly by using a ratio bone segment to whole body. Quantitative scanning with 99mTc-pyrophosphate makes it possible to: 1) detect bone metastases easily, 2) follow the metastases during treatment, 3) avoid the gross errors that can be made in nomquantitative scanning.", "contents": "[A quantitative and quanlitative examination of bone metastases by whole body scanning with 99mTc-pyrophosphate (author's transl)]. The purpose of the present work is to \"quantify\" bone scanning, in order to calculate indices of localized uptake that will make it possible to differentiate between normal and pathological uptake, and approach an etiologicial diagnosis. The authors use an Elscint dual head whole body scanner and an offline video display calculator. The patient is given 8 mc technetium 99m pyrophosphate 4 hours prior to scanning. The whole body count is expressed in thousands of counts multipled by two so that the knee to whole body ratio is close to one, to facilitate comparison of the indices. Results show that the presence of metastases is demonstrated more clearly by using a ratio bone segment to whole body. Quantitative scanning with 99mTc-pyrophosphate makes it possible to: 1) detect bone metastases easily, 2) follow the metastases during treatment, 3) avoid the gross errors that can be made in nomquantitative scanning."}
{"id": "PMID:186602", "title": "Effect of prolactin and growth hormone on prolactin and LH receptors in the dwarf mouse.", "content": "Dwarf mice (DW/J;dw/dw) which exhibit a deficiency of prolactin and GH secretion were treated for 8 days with ovine prolactin and/or human GH (10 or 20 mug/day) and the effect on hepatic and testicular prolactin receptors was investigated. In both sexes there was a significant increase in body weight after all hormone treatments, but an increment in testicular weight was observed only after prolactin administration. Prolactin treatment increased the specific binding % of prolactin in liver membranes in females but not males, and in testicular homogenates (together with an increase in LH receptors). The results suggest that lack of prolactin but not of GH retards sexual development in these mice. Treatment with prolactin partly counteracts this deficiency, and the effect may be mediated by the induction of hepatic and testicular prolactin and LH receptors.", "contents": "Effect of prolactin and growth hormone on prolactin and LH receptors in the dwarf mouse. Dwarf mice (DW/J;dw/dw) which exhibit a deficiency of prolactin and GH secretion were treated for 8 days with ovine prolactin and/or human GH (10 or 20 mug/day) and the effect on hepatic and testicular prolactin receptors was investigated. In both sexes there was a significant increase in body weight after all hormone treatments, but an increment in testicular weight was observed only after prolactin administration. Prolactin treatment increased the specific binding % of prolactin in liver membranes in females but not males, and in testicular homogenates (together with an increase in LH receptors). The results suggest that lack of prolactin but not of GH retards sexual development in these mice. Treatment with prolactin partly counteracts this deficiency, and the effect may be mediated by the induction of hepatic and testicular prolactin and LH receptors."}
{"id": "PMID:186603", "title": "Dysfunctional uterine bleeding.", "content": "The etiology and pathogenesis of dysfunctional uterine bleeding are discussed. For both age groups, adolescents and perimenopausal women, gonadotropin-steroid patterns as well as endometrial changes are presented. Methods of evaluation and therapy are described, including curettage and judicious of estrogen-progestogen combinations. Finally, long-term follow-ups of these patients are presented, with plans for reevaluation as well as palliative treatment based on the bleeding patterns and gonadotropin levels.", "contents": "Dysfunctional uterine bleeding. The etiology and pathogenesis of dysfunctional uterine bleeding are discussed. For both age groups, adolescents and perimenopausal women, gonadotropin-steroid patterns as well as endometrial changes are presented. Methods of evaluation and therapy are described, including curettage and judicious of estrogen-progestogen combinations. Finally, long-term follow-ups of these patients are presented, with plans for reevaluation as well as palliative treatment based on the bleeding patterns and gonadotropin levels."}
{"id": "PMID:186604", "title": "Structure of the peptide antibiotic polypeptin.", "content": "Polypeptin, a basic peptide antibiotic isolated from Bacillus circulans, was separated into two components by countercurrent distribution. The two components, polypeptin A and polypeptin B, had identical amino acid compositions but varied in the structure of the hydroxy acid constituent attached to the alpha-amino group of the peptide chain. Polypeptin A contained 3-hydrosy-4-methylhexanoic acid and polypeptin B contained 3-hydrosy-5-methylhexanoic acid. T-HE STEROCHEMISTRY OF THESE HYDROXY ACIDS WAS NOT DETERMINED. Studies involving partial acid hydrolysis and chemical synthesis are consistent with the lactone sturcture for polypeptin A. Polypeptin B differs only in the position of the methyl group in the hydroxyacyl moiety.", "contents": "Structure of the peptide antibiotic polypeptin. Polypeptin, a basic peptide antibiotic isolated from Bacillus circulans, was separated into two components by countercurrent distribution. The two components, polypeptin A and polypeptin B, had identical amino acid compositions but varied in the structure of the hydroxy acid constituent attached to the alpha-amino group of the peptide chain. Polypeptin A contained 3-hydrosy-4-methylhexanoic acid and polypeptin B contained 3-hydrosy-5-methylhexanoic acid. T-HE STEROCHEMISTRY OF THESE HYDROXY ACIDS WAS NOT DETERMINED. Studies involving partial acid hydrolysis and chemical synthesis are consistent with the lactone sturcture for polypeptin A. Polypeptin B differs only in the position of the methyl group in the hydroxyacyl moiety."}
{"id": "PMID:186605", "title": "Adrenocorticotropin. 49.1 Synthesis and biological activity of [2-delta-aminovaleric acid, 5-arginine-a1adrenocorticotropin-(2-19).", "content": "An adrenocorticotropin analogue, [2-delta-aminovaleric acid, 5-arginine]adrenocorticotropin-(2-19), has been synthesized by the solid-phase method and its biological activity has been determined. It was found that substitution of arginine for glutamic acid at position 5 of [2-delta-aminovaleric acid]adrenocorticotropin-(2-19) increased the steroidogenic potency in idolated rat adrenal cells and the lipolytic potency in isolated rat fat cells but decreased the lipolytic potency in isolated rabbit fat cells. The synthetic analogue had only 2% of the melanotropic potency of the parent molecule.", "contents": "Adrenocorticotropin. 49.1 Synthesis and biological activity of [2-delta-aminovaleric acid, 5-arginine-a1adrenocorticotropin-(2-19). An adrenocorticotropin analogue, [2-delta-aminovaleric acid, 5-arginine]adrenocorticotropin-(2-19), has been synthesized by the solid-phase method and its biological activity has been determined. It was found that substitution of arginine for glutamic acid at position 5 of [2-delta-aminovaleric acid]adrenocorticotropin-(2-19) increased the steroidogenic potency in idolated rat adrenal cells and the lipolytic potency in isolated rat fat cells but decreased the lipolytic potency in isolated rabbit fat cells. The synthetic analogue had only 2% of the melanotropic potency of the parent molecule."}
{"id": "PMID:186606", "title": "Action of insulin and cell calcium: effect of ionophore A23187.", "content": "We have measured the effects of the carboxylic Ca++ ionophore A23187 on muscle tension, resting potential and 3-O-methylglucose efflux. The ionophore produces an increase in tension that is dependent on external Ca++ concentration since (a) the contracture was blocked by removing external Ca++ and (b) its size was increased by raising outside Ca++. Neither resting potential nor resting and insulin-stimulated sugar efflux were modified by the ionophore. These data imply that the action of insulin is not mediated by increasing cytoplasmic [Ca++]. Additional support for this conclusion was obtained by testing the effects of caffeine on sugar efflux. This agent, which releases Ca++ from the reticulum, did not increase resting sugar efflux and inhibited the insulin-stimulated efflux. Incubation in solutions containing butyrated derivatives of cyclic AMP or cyclic GMP plus theophylline did not modify the effects of insulin on sugar efflux. Evidence suggesting that our experimental conditions increased the cytoplasmic cyclic AMP activity was obtained.", "contents": "Action of insulin and cell calcium: effect of ionophore A23187. We have measured the effects of the carboxylic Ca++ ionophore A23187 on muscle tension, resting potential and 3-O-methylglucose efflux. The ionophore produces an increase in tension that is dependent on external Ca++ concentration since (a) the contracture was blocked by removing external Ca++ and (b) its size was increased by raising outside Ca++. Neither resting potential nor resting and insulin-stimulated sugar efflux were modified by the ionophore. These data imply that the action of insulin is not mediated by increasing cytoplasmic [Ca++]. Additional support for this conclusion was obtained by testing the effects of caffeine on sugar efflux. This agent, which releases Ca++ from the reticulum, did not increase resting sugar efflux and inhibited the insulin-stimulated efflux. Incubation in solutions containing butyrated derivatives of cyclic AMP or cyclic GMP plus theophylline did not modify the effects of insulin on sugar efflux. Evidence suggesting that our experimental conditions increased the cytoplasmic cyclic AMP activity was obtained."}
{"id": "PMID:186611", "title": "Evaluation of BCG administered by scarification for immunotherapy of metastatic hepatocarcinoma in the guinea pig.", "content": "In inbred guinea pigs, administration of Mycobacterium bovis strain BCG by scarification at a site distant from an excised skin tumor, but in the regional lymph node drainage, was evaluated for its immunotherapeutic effect on the development of lymph node metastases. Scarification was performed after surgical excision of intradermally transplanted syngeneic (line-10) hepatocarcinoma at a time when microscopic foci of tumor cells were present in regional lymph nodes. Various strains of BCG were evaluated for their immunotherapeutic potential: fresh-frozen Phipps, Pasteur, and Tice; and lyophilized Pasteur, Tice, and Connaught. Scarification commenced 3 days after surgical removal of the tumor and continued once a week for 5 weeks. Only lymph nodes from fresh-frozen Phipps- and Pasteur-scarified animals were significantly smaller than those in the control groups. Differences in lymph node weight correlated histologically with less detectable metastases. This cytostatic effect was short lived; eventually, the metastatic tumor growth was not significantly different from that of control animals. No significant differences were observed in mean survival time: All animals died as a result of metastases 3 months after tumor inoculation. These results demonstrated that limited scarification with BCG of certain strains temporarily inhibits the growth and proliferation of metastases in regional lymph nodes after removal of the primary tumor.", "contents": "Evaluation of BCG administered by scarification for immunotherapy of metastatic hepatocarcinoma in the guinea pig. In inbred guinea pigs, administration of Mycobacterium bovis strain BCG by scarification at a site distant from an excised skin tumor, but in the regional lymph node drainage, was evaluated for its immunotherapeutic effect on the development of lymph node metastases. Scarification was performed after surgical excision of intradermally transplanted syngeneic (line-10) hepatocarcinoma at a time when microscopic foci of tumor cells were present in regional lymph nodes. Various strains of BCG were evaluated for their immunotherapeutic potential: fresh-frozen Phipps, Pasteur, and Tice; and lyophilized Pasteur, Tice, and Connaught. Scarification commenced 3 days after surgical removal of the tumor and continued once a week for 5 weeks. Only lymph nodes from fresh-frozen Phipps- and Pasteur-scarified animals were significantly smaller than those in the control groups. Differences in lymph node weight correlated histologically with less detectable metastases. This cytostatic effect was short lived; eventually, the metastatic tumor growth was not significantly different from that of control animals. No significant differences were observed in mean survival time: All animals died as a result of metastases 3 months after tumor inoculation. These results demonstrated that limited scarification with BCG of certain strains temporarily inhibits the growth and proliferation of metastases in regional lymph nodes after removal of the primary tumor."}
{"id": "PMID:186612", "title": "Antibody-induced modulation and shedding of mammary tumor virus antigens on the surfaces of GR ascites leukemia cells as compared with normal antigens.", "content": "The distribution, antibody-induced redistribution, and shedding of murine mammary tumor virus (MuMTV) antigens and the surfaces of GR mouse ascites leukemia (GRSL) cells were studied by the immunoferritin technique and compared with the same activities of thy 1.2 and H-2.8 antigens. MuMTV antigens were redistributed easily and then largely shed from the cell surface; in contrast, H-2.8 antigen moved easily and probably was partially released from the plasms membrane and Thy 1.2 antigen moved slowly and was some what interiorized. The complement-dependent cytotoxicity test was used to study the possibility of antigenic modulation for these cell-surface antigens from the surface of the GRSL cells could be modulated by preincubation with anti-MuMTV serum, in contrast to H-2.8 and Thy 1.2 antigens. The results obtained with the immunoferritin technique and the cytotoxicity test correlated well and sug-ested that the shedding of MuMTV antigens from the cell surfaces may occur in vivo, providing the tumor a way to escape from the immune defense of the host. Thy 1.2 and H-2.8 antigens were present on the envolope of B and C particles, which suggested that these viruses do not select a Thy 1.2 or H-2.8-negative area of the GRSL cell surface as amaturation site.", "contents": "Antibody-induced modulation and shedding of mammary tumor virus antigens on the surfaces of GR ascites leukemia cells as compared with normal antigens. The distribution, antibody-induced redistribution, and shedding of murine mammary tumor virus (MuMTV) antigens and the surfaces of GR mouse ascites leukemia (GRSL) cells were studied by the immunoferritin technique and compared with the same activities of thy 1.2 and H-2.8 antigens. MuMTV antigens were redistributed easily and then largely shed from the cell surface; in contrast, H-2.8 antigen moved easily and probably was partially released from the plasms membrane and Thy 1.2 antigen moved slowly and was some what interiorized. The complement-dependent cytotoxicity test was used to study the possibility of antigenic modulation for these cell-surface antigens from the surface of the GRSL cells could be modulated by preincubation with anti-MuMTV serum, in contrast to H-2.8 and Thy 1.2 antigens. The results obtained with the immunoferritin technique and the cytotoxicity test correlated well and sug-ested that the shedding of MuMTV antigens from the cell surfaces may occur in vivo, providing the tumor a way to escape from the immune defense of the host. Thy 1.2 and H-2.8 antigens were present on the envolope of B and C particles, which suggested that these viruses do not select a Thy 1.2 or H-2.8-negative area of the GRSL cell surface as amaturation site."}
{"id": "PMID:186613", "title": "Immunofluorescence and histologic studies of virus-induced murine lymphocytic leukemias.", "content": "Mice were inoculated with either the lymphatic leukemia virus associated with Friend and Rauscher viruses or with the Graffi or BALB/Tennant leukemia viruses. A total of 48 leukemic mice were examined histologically and by immunofluorescence. All four viruses induced a histologically similar disease that particularly involved tha thymus-dependent lymphoid regions. Lymphocytes from the spleens and thymuses of leukemic animals were examined for Thy-1 antigen and immunoglobulins on the cell surface; all the leukemias were composed of T- cells and/or nonreactive cells lacking both the Thy-1 antigen and immunoglobulins. By immunofluorescence, the spleen and thymus from the same leukemic animal frequently showed different cell-surface markers, though no morphologic differences were seen in leukemias involving the different classes of lymphocytes.", "contents": "Immunofluorescence and histologic studies of virus-induced murine lymphocytic leukemias. Mice were inoculated with either the lymphatic leukemia virus associated with Friend and Rauscher viruses or with the Graffi or BALB/Tennant leukemia viruses. A total of 48 leukemic mice were examined histologically and by immunofluorescence. All four viruses induced a histologically similar disease that particularly involved tha thymus-dependent lymphoid regions. Lymphocytes from the spleens and thymuses of leukemic animals were examined for Thy-1 antigen and immunoglobulins on the cell surface; all the leukemias were composed of T- cells and/or nonreactive cells lacking both the Thy-1 antigen and immunoglobulins. By immunofluorescence, the spleen and thymus from the same leukemic animal frequently showed different cell-surface markers, though no morphologic differences were seen in leukemias involving the different classes of lymphocytes."}
{"id": "PMID:186614", "title": "Oncornavirus-like particles in baboon type C virus-infected chimpanzee lung cells (SFRE:CL-1).", "content": "Intracytoplasmic type A particles were observed in a fetal chimpanzee lung culture (SFRE:CL-1) inoculated with type C virus-containing supernatants from a coculture of baboon placenta and SFRE:CL-1 cells. Budding, immature, and mature type C particles were also noted. In thin section, spike-like structures were rarely detected on budding intracytoplasmic type A particles but were occasionally observed on some immature and mature virus particles. Unlike mouse mammary tumor virus or Mason-Pfizer monkey virus, infected SFRE:CL-1 cells contained no eccentric or rodshaped nucleoids.", "contents": "Oncornavirus-like particles in baboon type C virus-infected chimpanzee lung cells (SFRE:CL-1). Intracytoplasmic type A particles were observed in a fetal chimpanzee lung culture (SFRE:CL-1) inoculated with type C virus-containing supernatants from a coculture of baboon placenta and SFRE:CL-1 cells. Budding, immature, and mature type C particles were also noted. In thin section, spike-like structures were rarely detected on budding intracytoplasmic type A particles but were occasionally observed on some immature and mature virus particles. Unlike mouse mammary tumor virus or Mason-Pfizer monkey virus, infected SFRE:CL-1 cells contained no eccentric or rodshaped nucleoids."}
{"id": "PMID:186615", "title": "Chronic Herpesvirus saimiri infection in an owl monkey.", "content": "An adult owl monkey (Aotus tricirgatus) used for immunologic studies of Herpesvirus saimiri (HVS) developed early, late, membrane, and neutralizing antibodies to HVS approximately 3 weeks after the beginning of the experiment. HVS was isolated by the cocultivation of peripheral blood for over 1 year. No clinical, gross, or histopathologic findings of malignancy were exhibited by the animal. The HVS isolate from the animal was indistinguishable biologically and serologically from the original HVS strain of Mel\u00e9ndez and from an isolate of an experimentally HVS-induced tumor. Inoculation of this isolate into 2 young white-lipped marmosets (Saguinus fuscicollis) produced typical malignant lymphoma and lymphocytic leukemia. Our findings suggested that the virus from the chronically infected animal was oncogenic and that host factors were primarily responsible for determining the disease manifestation of the virus infection. Another owl monkey chronically infected with HVS for over 2 years has remained asymptomatic.", "contents": "Chronic Herpesvirus saimiri infection in an owl monkey. An adult owl monkey (Aotus tricirgatus) used for immunologic studies of Herpesvirus saimiri (HVS) developed early, late, membrane, and neutralizing antibodies to HVS approximately 3 weeks after the beginning of the experiment. HVS was isolated by the cocultivation of peripheral blood for over 1 year. No clinical, gross, or histopathologic findings of malignancy were exhibited by the animal. The HVS isolate from the animal was indistinguishable biologically and serologically from the original HVS strain of Mel\u00e9ndez and from an isolate of an experimentally HVS-induced tumor. Inoculation of this isolate into 2 young white-lipped marmosets (Saguinus fuscicollis) produced typical malignant lymphoma and lymphocytic leukemia. Our findings suggested that the virus from the chronically infected animal was oncogenic and that host factors were primarily responsible for determining the disease manifestation of the virus infection. Another owl monkey chronically infected with HVS for over 2 years has remained asymptomatic."}
{"id": "PMID:186616", "title": "Effect of allelic substitutions at the hairless locus on endogenous ecotropic murine leukemia virus titers and leukemogenesis.", "content": "Leukemia-prone hairless (HRS/J; hr/hr) mice had significantly higher leukemia virus titers than did the leukemia-resistant nonmutants (hr/ + and +/+). This difference was ascribed to the allelic substitution at a single gene locus; at 6 months of age it averaged 13-fold, immediately preceding the large divergence in leukemia incidence between the mutant and nonmutant mice.", "contents": "Effect of allelic substitutions at the hairless locus on endogenous ecotropic murine leukemia virus titers and leukemogenesis. Leukemia-prone hairless (HRS/J; hr/hr) mice had significantly higher leukemia virus titers than did the leukemia-resistant nonmutants (hr/ + and +/+). This difference was ascribed to the allelic substitution at a single gene locus; at 6 months of age it averaged 13-fold, immediately preceding the large divergence in leukemia incidence between the mutant and nonmutant mice."}
{"id": "PMID:186617", "title": "Cell-mediated immunity in mice against papain-solubilized histocompatibility and tumor-specific antigens by a macrophage migration inhibition microassay.", "content": "The cell-mediated immune status of B10.D2 (H-2d) mice immunized with spleen cells from a congenic strain, B10.A (H-2a), differing at the H-2 locus and of BALB/c mice immunized with a syngeneic simian virus 40 (SV40)-induced sarcoma (mKSA-TU5) was evaluated by an agarose microassay for migration inhibition factor. The inducing antigens in this experiment were papain-solubilized and partially purified chromatographic preparations of spleen cells from A/J mice (H-2a) and a papain-solubilized antigen extract prepared from a tissue culture-adapted cell line (TU-5), derived from the SV40-induced mKSA tumor. The assay used microliters of normal or immune peritoneal exudate cells (PEC) resuspended in a 2-mul droplet of agarose and cultured in the presence or absence of antigen. Specific migration inhibition of PEC from immunized mice was observed with concentrations of solubilized antigen preparations as low as 2.0 mug/ml (3.67 mug/chamber).", "contents": "Cell-mediated immunity in mice against papain-solubilized histocompatibility and tumor-specific antigens by a macrophage migration inhibition microassay. The cell-mediated immune status of B10.D2 (H-2d) mice immunized with spleen cells from a congenic strain, B10.A (H-2a), differing at the H-2 locus and of BALB/c mice immunized with a syngeneic simian virus 40 (SV40)-induced sarcoma (mKSA-TU5) was evaluated by an agarose microassay for migration inhibition factor. The inducing antigens in this experiment were papain-solubilized and partially purified chromatographic preparations of spleen cells from A/J mice (H-2a) and a papain-solubilized antigen extract prepared from a tissue culture-adapted cell line (TU-5), derived from the SV40-induced mKSA tumor. The assay used microliters of normal or immune peritoneal exudate cells (PEC) resuspended in a 2-mul droplet of agarose and cultured in the presence or absence of antigen. Specific migration inhibition of PEC from immunized mice was observed with concentrations of solubilized antigen preparations as low as 2.0 mug/ml (3.67 mug/chamber)."}
{"id": "PMID:186618", "title": "Immunostimulation of cytomegalovirus-transformed cells and its inhibition by blocking sera.", "content": "Spleen cells cytotoxic at high effector cell: target cell ratios specifically enhanced target cell survival at low ratios. Both cytotoxicity and immunostimulation could be specifically blocked by sera from tumor-bearing or virus-sensitized hosts. The results suggested that serum factors participate in the regulation of the cell-mediated immune response.", "contents": "Immunostimulation of cytomegalovirus-transformed cells and its inhibition by blocking sera. Spleen cells cytotoxic at high effector cell: target cell ratios specifically enhanced target cell survival at low ratios. Both cytotoxicity and immunostimulation could be specifically blocked by sera from tumor-bearing or virus-sensitized hosts. The results suggested that serum factors participate in the regulation of the cell-mediated immune response."}
{"id": "PMID:186619", "title": "Characteristics of a human cell line successively transformed by Rous sarcoma virus and simian virus 40.", "content": "Human enbryo cells were successively transformed by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) and simian virus 40 (SV40) in vitro, and the double transformant HuE 13 RS was established. From this cell line the two clonal cell lines RSa and RSb were isolated. In both, presence of SV40 T antigens was demonstrated by the fluorescent antibody technique, and the presence of RSV genomes was verified in one RSb clone by focus formation after fusion with chick embryo cells. Growth of these cells was affected by dibutyryl cAMP without marked morphologic changes. Cells were extremely sensitive to the anticellular action of human leukocyte interferon.", "contents": "Characteristics of a human cell line successively transformed by Rous sarcoma virus and simian virus 40. Human enbryo cells were successively transformed by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) and simian virus 40 (SV40) in vitro, and the double transformant HuE 13 RS was established. From this cell line the two clonal cell lines RSa and RSb were isolated. In both, presence of SV40 T antigens was demonstrated by the fluorescent antibody technique, and the presence of RSV genomes was verified in one RSb clone by focus formation after fusion with chick embryo cells. Growth of these cells was affected by dibutyryl cAMP without marked morphologic changes. Cells were extremely sensitive to the anticellular action of human leukocyte interferon."}
{"id": "PMID:186620", "title": "Spontaneous tumors and common diseases in two colonies of Syrian hamsters. II. Respiratory tract and digestive system.", "content": "Spontaneous respiratory tract neoplasms in Syrian hamsters occurred in almost equal frequencies in two colonies: 3% in the Eppley Colony (EC) and 3.6% in the Hannover Colony (HC). Neoplasms were in the nasal cavity, trachea, and lungs, and most were benign; however, 2 adenocarcinomas of the nasal cavity (EC) and 1 adenocarcinoma of the larynx (HC) were found. The incidence of digestive tract tumors showed a more marked difference than that of the respiratory tract: 7% in the EC and 23% in the HC. Digestive tract tumors accounted for 15 and 41% of all tumors in the EC and HC, respectively. All EC digestive tract neoplasms were benign and occurred mostly in males; 19 (83%) were forestomach papillomas and the remaining 4 )17%) were liver hemangioendotheliomas (2) and pancreatic duct adenomas (2). In the HC, almost 50% of the digestive tract neoplasms were malignant and most frequent in females. These tumours include 19(42%) intestinal adenocarcinomas, 18(40%) liver neoplasms (hemangioendotheliomas, cholangiomas, cholangiocarcinomas), 5 (13%) forestomach papillomas, and 2 (4%) gallbladder polyps. The morphology of these neoplasms was reported.", "contents": "Spontaneous tumors and common diseases in two colonies of Syrian hamsters. II. Respiratory tract and digestive system. Spontaneous respiratory tract neoplasms in Syrian hamsters occurred in almost equal frequencies in two colonies: 3% in the Eppley Colony (EC) and 3.6% in the Hannover Colony (HC). Neoplasms were in the nasal cavity, trachea, and lungs, and most were benign; however, 2 adenocarcinomas of the nasal cavity (EC) and 1 adenocarcinoma of the larynx (HC) were found. The incidence of digestive tract tumors showed a more marked difference than that of the respiratory tract: 7% in the EC and 23% in the HC. Digestive tract tumors accounted for 15 and 41% of all tumors in the EC and HC, respectively. All EC digestive tract neoplasms were benign and occurred mostly in males; 19 (83%) were forestomach papillomas and the remaining 4 )17%) were liver hemangioendotheliomas (2) and pancreatic duct adenomas (2). In the HC, almost 50% of the digestive tract neoplasms were malignant and most frequent in females. These tumours include 19(42%) intestinal adenocarcinomas, 18(40%) liver neoplasms (hemangioendotheliomas, cholangiomas, cholangiocarcinomas), 5 (13%) forestomach papillomas, and 2 (4%) gallbladder polyps. The morphology of these neoplasms was reported."}
{"id": "PMID:186621", "title": "Transformation of tonsil lymphocytes by Epstein-Barr virus.", "content": "Tonsil lymphocytes obtained from children and adults at tonsillectomy were examined for susceptibility to infection with Epstein-Barr virus (EBV) in vitro. Of 37 specimens, 24 (65%) were transformed by EBV. Rate of transformation was higher in the cells from younger children than in those from older children and adults, but the susceptibility was not directly correlated to the titer of antibody against EBV in donor serum. All 22 transformed tonsil cell lines tested were carrying EBV-associated nuclear antigen, and 8 of them produced cytoplasmic IgA in 15-45% of cells. The results suggest that tonsil lymphocytes are targets of EBV.", "contents": "Transformation of tonsil lymphocytes by Epstein-Barr virus. Tonsil lymphocytes obtained from children and adults at tonsillectomy were examined for susceptibility to infection with Epstein-Barr virus (EBV) in vitro. Of 37 specimens, 24 (65%) were transformed by EBV. Rate of transformation was higher in the cells from younger children than in those from older children and adults, but the susceptibility was not directly correlated to the titer of antibody against EBV in donor serum. All 22 transformed tonsil cell lines tested were carrying EBV-associated nuclear antigen, and 8 of them produced cytoplasmic IgA in 15-45% of cells. The results suggest that tonsil lymphocytes are targets of EBV."}
{"id": "PMID:186622", "title": "Cellular immunity in rats with primary brain tumors: inhibition of macrophage migration by soluble extracts of avian sarcoma virus-induced tumors.", "content": "Rats bearing primary tumors of the brain induced by avian sarcoma virus (ASV) were studied with the migration-inhibition factor (MIF) assay for the presence of cell-mediated immunity to tumor-associated antigens. Astrocytomas and sarcomas of the brain were induced in 34 neonatal F344 rats by the intracerebral inoculation of Bratislava-77 ASV. At weekly intervals from 4 to 9 weeks after the inoculation with virus, peritoneal exudate cells (PEC) from rats bearing brain tumors were tested an an MIF assay against soluble and KCl-treated extracts of a syngeneic, ASV-induced sarcoma. Incubation of the PEC with a soluble extract of syngeneic liver or with a KCl extract of a syngeneic, chemically induced tumor served as controls. Of 14 rats tested against the soluble tumor extract, 6 (43%) had statistically significant inhibition of migration (P less than or equal to 0.05). Of 23 animals tested against the KCl extract, 16 (70%) had significant inhibition. Immunity to the KCl extract was significant in most rats at each  period. Ten rats were tested against a KCl extract of a hamster ASV-induced tumor; 7 gad significant inhibition of migration. None of 3 tested against a soluble extract of a syngeneic, chemically induced tumor had significant inhibition. Rats bearing ASV-induced brain tumors displayed cell-mediated immunity to tumor-associated antigen or antigens of ASV-induced tumors, which could be solubilized.", "contents": "Cellular immunity in rats with primary brain tumors: inhibition of macrophage migration by soluble extracts of avian sarcoma virus-induced tumors. Rats bearing primary tumors of the brain induced by avian sarcoma virus (ASV) were studied with the migration-inhibition factor (MIF) assay for the presence of cell-mediated immunity to tumor-associated antigens. Astrocytomas and sarcomas of the brain were induced in 34 neonatal F344 rats by the intracerebral inoculation of Bratislava-77 ASV. At weekly intervals from 4 to 9 weeks after the inoculation with virus, peritoneal exudate cells (PEC) from rats bearing brain tumors were tested an an MIF assay against soluble and KCl-treated extracts of a syngeneic, ASV-induced sarcoma. Incubation of the PEC with a soluble extract of syngeneic liver or with a KCl extract of a syngeneic, chemically induced tumor served as controls. Of 14 rats tested against the soluble tumor extract, 6 (43%) had statistically significant inhibition of migration (P less than or equal to 0.05). Of 23 animals tested against the KCl extract, 16 (70%) had significant inhibition. Immunity to the KCl extract was significant in most rats at each  period. Ten rats were tested against a KCl extract of a hamster ASV-induced tumor; 7 gad significant inhibition of migration. None of 3 tested against a soluble extract of a syngeneic, chemically induced tumor had significant inhibition. Rats bearing ASV-induced brain tumors displayed cell-mediated immunity to tumor-associated antigen or antigens of ASV-induced tumors, which could be solubilized."}
{"id": "PMID:186623", "title": "Feline oncornavirus-associated cell membrane antigen. VI. Cytotoxic antibody in cats exposed to feline leukemia virus.", "content": "Feline leukemia virus (FeLV)-infected specific pathogen-free (SPF) cats, normal uninfected SPF cats, and healthy cats from leukemic households were tested for antibody reactive to the feline oncornavirus-associated cell membrane antigen (FOCMA)-containing target cell line FL-74 by microcytotoxicity and indirect membrane immunofluorescence. Of the infected SPF animals, 81% showed concordant reactivity for the two tests. In contrast, only 55% of the healthy cats known to be naturally exposed to FeLV for long periods showed such concordance. FOCMA antibody could not be detected in normal SPF cats by either indirect membrane immunofluorescence or microcytotoxicity. Most cats in the FeLV-infected SPF group developed antibody detectable by both procedures by the fifth week post inoculation. Antibody detectable by membrane immunofluorescence persisted in a high percentage (75-90%) of the animals throughout the observation period of 19 weeks; after 9 weeks, fewer cats had antibody that was also detectable by microcytotoxicity.", "contents": "Feline oncornavirus-associated cell membrane antigen. VI. Cytotoxic antibody in cats exposed to feline leukemia virus. Feline leukemia virus (FeLV)-infected specific pathogen-free (SPF) cats, normal uninfected SPF cats, and healthy cats from leukemic households were tested for antibody reactive to the feline oncornavirus-associated cell membrane antigen (FOCMA)-containing target cell line FL-74 by microcytotoxicity and indirect membrane immunofluorescence. Of the infected SPF animals, 81% showed concordant reactivity for the two tests. In contrast, only 55% of the healthy cats known to be naturally exposed to FeLV for long periods showed such concordance. FOCMA antibody could not be detected in normal SPF cats by either indirect membrane immunofluorescence or microcytotoxicity. Most cats in the FeLV-infected SPF group developed antibody detectable by both procedures by the fifth week post inoculation. Antibody detectable by membrane immunofluorescence persisted in a high percentage (75-90%) of the animals throughout the observation period of 19 weeks; after 9 weeks, fewer cats had antibody that was also detectable by microcytotoxicity."}
{"id": "PMID:186624", "title": "Transplantation of human tumors in nude mice.", "content": "Ninety-one human tumors, including various common carcinomas, low-grade malignant tumors, and benign tumors, were transplanted into athymic nude mice. Tumor take was confirmed histologically for 22 neoplasms at the initial transplantation, and 14 serially transplantable tumors were established, including some hitherto unestablished or unreported, such as lung and hepatic cell carcinomas. Among the 91 tumors were 21, 14, and 13 carcinomas of the lung, stomach, and breast, respectively. Transplantability was highest in lung carcinomas (10/21), followed by gastric carcinomas (2/14) and breast carcinomas (1/13). Morphology of original tumors was retained well in most transplanted tumors, but desmoplastic or scirrhous tumors, such as gastric and breast carcinomas, tended to become medullary with a decrease in amount of tumor stroma. The ability to produce mucin in gastric carcinomas or melanin in malignant melanoma was maintained in serially transplantable tumors. In addition, ectopic production of adrenocorticotropin and beta melanocyte-stimulating hormone continued in a transplanted small cell carcinoma of the lung. Preliminary results were obtained on hormone dependency of the transplantable breast carcinoma and on alpha1-fetoprotein in the transplantable hepatic cell carcinoma.", "contents": "Transplantation of human tumors in nude mice. Ninety-one human tumors, including various common carcinomas, low-grade malignant tumors, and benign tumors, were transplanted into athymic nude mice. Tumor take was confirmed histologically for 22 neoplasms at the initial transplantation, and 14 serially transplantable tumors were established, including some hitherto unestablished or unreported, such as lung and hepatic cell carcinomas. Among the 91 tumors were 21, 14, and 13 carcinomas of the lung, stomach, and breast, respectively. Transplantability was highest in lung carcinomas (10/21), followed by gastric carcinomas (2/14) and breast carcinomas (1/13). Morphology of original tumors was retained well in most transplanted tumors, but desmoplastic or scirrhous tumors, such as gastric and breast carcinomas, tended to become medullary with a decrease in amount of tumor stroma. The ability to produce mucin in gastric carcinomas or melanin in malignant melanoma was maintained in serially transplantable tumors. In addition, ectopic production of adrenocorticotropin and beta melanocyte-stimulating hormone continued in a transplanted small cell carcinoma of the lung. Preliminary results were obtained on hormone dependency of the transplantable breast carcinoma and on alpha1-fetoprotein in the transplantable hepatic cell carcinoma."}
{"id": "PMID:186625", "title": "Synthesis and half-life of a serum factor in normal and tumor-bearing animals.", "content": "The synthesis and disappearance of a serum factor from the circulating blood of rats bearing Morris hepatomas 7777 or 7800 were described. We provided evidence that the factor was synthesized by the livers of normal rats and continued to be synthesized in tumor-bearing animals. Despite very low levels in the sera of tumor-bearing animals, the factor was synthesized at twice the rate in these animals compared to that in normal rats. The half-life of the total serum protein was 2 days in normal rats and 2.9 days in hepatoma 7777-bearing animals. The half-life of the serum factor, on the other hand, was 23 hours in normal rats but only 9 hours in hepatoma-bearing rats. This rapid disappearance of the factor from the circulating blood, despite an increased synthesis, accounts for the complete absence of the factor in the sera of hepatoma-bearing animals with tumor weights larger than the liver weights.", "contents": "Synthesis and half-life of a serum factor in normal and tumor-bearing animals. The synthesis and disappearance of a serum factor from the circulating blood of rats bearing Morris hepatomas 7777 or 7800 were described. We provided evidence that the factor was synthesized by the livers of normal rats and continued to be synthesized in tumor-bearing animals. Despite very low levels in the sera of tumor-bearing animals, the factor was synthesized at twice the rate in these animals compared to that in normal rats. The half-life of the total serum protein was 2 days in normal rats and 2.9 days in hepatoma 7777-bearing animals. The half-life of the serum factor, on the other hand, was 23 hours in normal rats but only 9 hours in hepatoma-bearing rats. This rapid disappearance of the factor from the circulating blood, despite an increased synthesis, accounts for the complete absence of the factor in the sera of hepatoma-bearing animals with tumor weights larger than the liver weights."}
{"id": "PMID:186626", "title": "Formation of larger cell aggregates by transformed cells: an in vitro index of cell transformation.", "content": "Virus-transformed rat and hamster embryonic cells formed larger cell aggregates than those formed by normal counterpart cells within 1-3 days. This aggregate property correlated with growth in soft agar and tumorigenicity.", "contents": "Formation of larger cell aggregates by transformed cells: an in vitro index of cell transformation. Virus-transformed rat and hamster embryonic cells formed larger cell aggregates than those formed by normal counterpart cells within 1-3 days. This aggregate property correlated with growth in soft agar and tumorigenicity."}
{"id": "PMID:186627", "title": "Hormone synergism in the in vitro production of the mouse mammary tumor virus.", "content": "The production of mouse mammary tumor virus (MMTV) in primary cell cultures of BALB/cfC3H mammary tumor cells was measured by radioimmune assay and RNA=dependent DNA polymerase activity. Maximum virus production was dependent on cell density, nutritional milieu, and hormone supplementation. The addition of insulin (u), estradiol-17 beta (E2), progesterone (P), prolactin (PRL), or thyroxine (T3) alone had little or no effect on MMTV production. Hydrocortisone (F) had a primary stimulatory effect. The combination of I, F, and T3 increased MMTV levels. The combinations containing I, F, and E2 had the greatest stimulatory effect. The stimulation of MMTV production was dose dependent. These experiments demonstrate that a variety of hormones act in a synergistic manner to stimulate MMTV production.", "contents": "Hormone synergism in the in vitro production of the mouse mammary tumor virus. The production of mouse mammary tumor virus (MMTV) in primary cell cultures of BALB/cfC3H mammary tumor cells was measured by radioimmune assay and RNA=dependent DNA polymerase activity. Maximum virus production was dependent on cell density, nutritional milieu, and hormone supplementation. The addition of insulin (u), estradiol-17 beta (E2), progesterone (P), prolactin (PRL), or thyroxine (T3) alone had little or no effect on MMTV production. Hydrocortisone (F) had a primary stimulatory effect. The combination of I, F, and T3 increased MMTV levels. The combinations containing I, F, and E2 had the greatest stimulatory effect. The stimulation of MMTV production was dose dependent. These experiments demonstrate that a variety of hormones act in a synergistic manner to stimulate MMTV production."}
{"id": "PMID:186628", "title": "Steroid-binding proteins of the mammary gland and their clinical significance in breast cancer.", "content": "Differentiation and development of the mammary gland are influenced by estrogens, glucocorticoids, and progesterone. Specific binding sites for each of these classes of steroid hormones have been characterized in vivo and in cell-free preparations of lactating mammary gland of the rat. These properties were compared with those of steroid-binding proteins in the R3230AC and dimethylbenz[a]anthracene-induced mammary tumors of the rat and of human breast carcinomas. The binding components that were protein in nature were more concentrated in tissue from lactating than from virgin or pregnant rats. The steroid-binding capacities of mammary tumors were highly variable. Using a dextran-coated charcoal procedure, the rate constants of 3H-ligand association with specific binding sites were temperature dependent. Ligand specificity indicated that [3H]estradoil-17beta(3H-E) binding was inhibited only by estrogens, whereas [3H]triamcinolone acetonide (3 H-TA) was blocked by glucocorticoid/s and progesterone. Likewise, [3H]progesterone (3H-P) binding was inhibited by progestins and certain glucocorticoids. Incubation of minced mammary gland with 3H-steroid in the presence and absence of unlabeled competitor demonstrated specific binding sites in cytoplasm that were translocated to nuclei in a tempreature-dependent fashion. Using a steroid-exchange procedure both DEX and TA inhibited 3H-P binding to exchangeable sites that were loaded previously with unlabeled progesterone. These data suggest that certain glucocorticoid and progesterone binding sites were translocated simultaneously to nuclei. Administration in vivo of either 3H-E or 3H-TA indicated binding in cytoplasm and subsequent translocation to nuclei.", "contents": "Steroid-binding proteins of the mammary gland and their clinical significance in breast cancer. Differentiation and development of the mammary gland are influenced by estrogens, glucocorticoids, and progesterone. Specific binding sites for each of these classes of steroid hormones have been characterized in vivo and in cell-free preparations of lactating mammary gland of the rat. These properties were compared with those of steroid-binding proteins in the R3230AC and dimethylbenz[a]anthracene-induced mammary tumors of the rat and of human breast carcinomas. The binding components that were protein in nature were more concentrated in tissue from lactating than from virgin or pregnant rats. The steroid-binding capacities of mammary tumors were highly variable. Using a dextran-coated charcoal procedure, the rate constants of 3H-ligand association with specific binding sites were temperature dependent. Ligand specificity indicated that [3H]estradoil-17beta(3H-E) binding was inhibited only by estrogens, whereas [3H]triamcinolone acetonide (3 H-TA) was blocked by glucocorticoid/s and progesterone. Likewise, [3H]progesterone (3H-P) binding was inhibited by progestins and certain glucocorticoids. Incubation of minced mammary gland with 3H-steroid in the presence and absence of unlabeled competitor demonstrated specific binding sites in cytoplasm that were translocated to nuclei in a tempreature-dependent fashion. Using a steroid-exchange procedure both DEX and TA inhibited 3H-P binding to exchangeable sites that were loaded previously with unlabeled progesterone. These data suggest that certain glucocorticoid and progesterone binding sites were translocated simultaneously to nuclei. Administration in vivo of either 3H-E or 3H-TA indicated binding in cytoplasm and subsequent translocation to nuclei."}
{"id": "PMID:186629", "title": "Proteolytic enzyme activity in the granulation tissue of the human burn wound.", "content": "A procedure for adsorbing enzymes from the human burn wound onto solid sheets of substrate is described. Using this technique, low levels of enzyme activity with chymotrypsin-like specificity can be demonstrated in the wound approximately 2 weeks after injury. This activity disappears at about 5 weeks after the burn. The enzyme activity corresponds with the clinical experience for the time course of natural loss of the burn eschar. A trypsin-like enzyme of very low level activity is present in the wound. No collagenase was detected in the human burn wound. Preliminary evidence shows an additional leucine-specific enzyme in the human burn wound. A more detailed analysis of enzymes in the human burn wound should permit the development of a useful artificial debriding agent. Presently these preparations must be used with caution.", "contents": "Proteolytic enzyme activity in the granulation tissue of the human burn wound. A procedure for adsorbing enzymes from the human burn wound onto solid sheets of substrate is described. Using this technique, low levels of enzyme activity with chymotrypsin-like specificity can be demonstrated in the wound approximately 2 weeks after injury. This activity disappears at about 5 weeks after the burn. The enzyme activity corresponds with the clinical experience for the time course of natural loss of the burn eschar. A trypsin-like enzyme of very low level activity is present in the wound. No collagenase was detected in the human burn wound. Preliminary evidence shows an additional leucine-specific enzyme in the human burn wound. A more detailed analysis of enzymes in the human burn wound should permit the development of a useful artificial debriding agent. Presently these preparations must be used with caution."}
{"id": "PMID:186630", "title": "Neoplasms of the temporal bone.", "content": "A series of 209 patients with chemodectomas and malignant neoplasms of the external auditory canal and middle ear seen during a 20-year period at the Mayo Clinic was reviewed. Ninety-nine patients had chemodectomas, and 110 had malignant lesions; 57 of the 110 patients with malignancies had squamous cell carcinoma. The study revealed that patients with chemodectomas had a normal expected length of survival, whereas patients with malignant lesions (especially those with squamous cell carcinomas and embryonal rhabdomyosarcomas) did poorly.", "contents": "Neoplasms of the temporal bone. A series of 209 patients with chemodectomas and malignant neoplasms of the external auditory canal and middle ear seen during a 20-year period at the Mayo Clinic was reviewed. Ninety-nine patients had chemodectomas, and 110 had malignant lesions; 57 of the 110 patients with malignancies had squamous cell carcinoma. The study revealed that patients with chemodectomas had a normal expected length of survival, whereas patients with malignant lesions (especially those with squamous cell carcinomas and embryonal rhabdomyosarcomas) did poorly."}
{"id": "PMID:186631", "title": "Clinically relevant physiology of the vestibulo-ocular reflex.", "content": "This review attempts to explain those aspects of the physiology of the vestibulo-ocular reflex (VOR) which could be of future clinical value. The literature cited has been selected for its didactic worth to readers with limited time, preferring concise reviews to detailed reports wherever possible. Physiological data provide the background for the following possible improvements in clinical diagnosis: 1) In gaze analysis, coordination of the VOR with other motor patterns can be analyzed. 2) Precision of vestibular tests can be improved by selecting stimuli within the range of natural movements.3) Resolution of the caloric test can be imporved when the change of temperature at the semicircular canal mimics endolymph pressure changes during natural movements. 4) A direct test of the three neuron VOR pathways is possible, but not practicable. 5) Integration of the input signal (transformation from head acceleration to eye position information) can be directly tested. 6) Plasticity (the adaptation to visual requirements) of the VOR can be examined. 7) It is possible to quantify vestibular damage and detect the side of lesion in one test analyzing gain and binocular symmetry of the vertical VOR.", "contents": "Clinically relevant physiology of the vestibulo-ocular reflex. This review attempts to explain those aspects of the physiology of the vestibulo-ocular reflex (VOR) which could be of future clinical value. The literature cited has been selected for its didactic worth to readers with limited time, preferring concise reviews to detailed reports wherever possible. Physiological data provide the background for the following possible improvements in clinical diagnosis: 1) In gaze analysis, coordination of the VOR with other motor patterns can be analyzed. 2) Precision of vestibular tests can be improved by selecting stimuli within the range of natural movements.3) Resolution of the caloric test can be imporved when the change of temperature at the semicircular canal mimics endolymph pressure changes during natural movements. 4) A direct test of the three neuron VOR pathways is possible, but not practicable. 5) Integration of the input signal (transformation from head acceleration to eye position information) can be directly tested. 6) Plasticity (the adaptation to visual requirements) of the VOR can be examined. 7) It is possible to quantify vestibular damage and detect the side of lesion in one test analyzing gain and binocular symmetry of the vertical VOR."}
{"id": "PMID:186633", "title": "Content and expression of integrated viral DNA in hamster cells transformed by nondefective adenovirus type 2- simian virus 40 hybrid viruses.", "content": "Hamster cells transformed by adenovirus 2 (Ad2) and five nondefective Ad2-simian virus 40 (SV40) hybrid viruses are all of the Ad2-transformed phenotype. All lines accumulate Ad2 RNA and Ad2 T antigen; two hybrid-transformed lines accumulate SV40 RNA, but only one contains detectable amounts of SV40 antigens. We examines selected lines from this group of transformed hamster cells for Ad2 DNA content and viral RNA expression by using hydroxyapatite chromatography and separated strands of labeled viral DNA as probes. All lines studies contain 1 to 2 Ad2 genome equivalents per haploid equivalent of cell DNA. The expression of Ad2 RNA exhibits two distinct patterns. In one pattern, transcription of the heavy strand of Ad2 DNA is less than that of the light strand, whereas in the second pattern of Ad2 RNA expression the extent of heavy-strand transcription is greatly increased. In the two lines containing SV40 RNA, the entire SV40 (-) strand is transcribed; the (+) strand is not expressed in these cells. These patterns of viral RNA expression suggest the possibility that host promoters may play a role in regulating transcription of integrated viral DNA.", "contents": "Content and expression of integrated viral DNA in hamster cells transformed by nondefective adenovirus type 2- simian virus 40 hybrid viruses. Hamster cells transformed by adenovirus 2 (Ad2) and five nondefective Ad2-simian virus 40 (SV40) hybrid viruses are all of the Ad2-transformed phenotype. All lines accumulate Ad2 RNA and Ad2 T antigen; two hybrid-transformed lines accumulate SV40 RNA, but only one contains detectable amounts of SV40 antigens. We examines selected lines from this group of transformed hamster cells for Ad2 DNA content and viral RNA expression by using hydroxyapatite chromatography and separated strands of labeled viral DNA as probes. All lines studies contain 1 to 2 Ad2 genome equivalents per haploid equivalent of cell DNA. The expression of Ad2 RNA exhibits two distinct patterns. In one pattern, transcription of the heavy strand of Ad2 DNA is less than that of the light strand, whereas in the second pattern of Ad2 RNA expression the extent of heavy-strand transcription is greatly increased. In the two lines containing SV40 RNA, the entire SV40 (-) strand is transcribed; the (+) strand is not expressed in these cells. These patterns of viral RNA expression suggest the possibility that host promoters may play a role in regulating transcription of integrated viral DNA."}
{"id": "PMID:186634", "title": "Distinguishing cytomegalovirus, mycoplasma, and cellular DNA polymerases.", "content": "Cytomegalovirus-induced DNA polymerase can be distinguished from infected-cell enzymes by activity in 100 mM (NH4)2SO4. Virus polymerase is stimulated to 145% of control, whereas mock-infected cell polymerase is inhibited to 12% of control without added salt. Mycoplasmas induce a DNA polymerase in cell extracts that is stimulated to 130 to 180% by 25 mM (NH4)2SO4. Mycoplasma DNA polymerase may be mistaken for a virus-induced polymerase when virus stocks are contaminated. Identification of virus, cellular, and mycoplasma DNA polymerases in total cell extracts is described using sedimentation rate and effect of inhibitors on DNA polymerase activities.", "contents": "Distinguishing cytomegalovirus, mycoplasma, and cellular DNA polymerases. Cytomegalovirus-induced DNA polymerase can be distinguished from infected-cell enzymes by activity in 100 mM (NH4)2SO4. Virus polymerase is stimulated to 145% of control, whereas mock-infected cell polymerase is inhibited to 12% of control without added salt. Mycoplasmas induce a DNA polymerase in cell extracts that is stimulated to 130 to 180% by 25 mM (NH4)2SO4. Mycoplasma DNA polymerase may be mistaken for a virus-induced polymerase when virus stocks are contaminated. Identification of virus, cellular, and mycoplasma DNA polymerases in total cell extracts is described using sedimentation rate and effect of inhibitors on DNA polymerase activities."}
{"id": "PMID:186635", "title": "RNA synthesis in cells infected with herpes simple virus. XIII. Differences in the methylation patterns of viral RNA during the reproductive cycle.", "content": "Herpex simplex virus 1 (HSV-1) RNA labeled with with [methyl-3H] methionine at various times during the infectious cycle and purified by hybridization to viral DNA was analyzed for the presence of methylated nucleotides. The data indicate the following. (i) RNA labeled from 0 to 14 h postinfection and accumulating in the cytoplasm contained internal base-methylated nucleotides and terminal oligonucleotides consistent with the structure 7mG(5')ppp-(5')XmpYmpNp. Similar methylated nucleotides and oligonucleotides were also found in viral RNA accumulating in the cytoplasm of cells treated with cycloheximide from the time of infection. Previous studies (M. Kozak and B. Roizman, 1974) have shown that, whereas the RNA accumulating in the 14-h infected cells contains all of the sequences functioning as mRNA throughout infection, the RNA accumulating in the cytoplasm of cycloheximide-treated cells is associated with polyribosomes synthesizing the earliest (alpha) group of polypeptides specified by the virus. (ii) Cytoplasmic viral RNA from cells labeled 11 to 14 h postinfection as well as the total adenylated RNA in the cytoplasm and polyribosomes labeled in the same fashion contained the terminal oligonucleotide but not the internal base-methylated nucleotide.", "contents": "RNA synthesis in cells infected with herpes simple virus. XIII. Differences in the methylation patterns of viral RNA during the reproductive cycle. Herpex simplex virus 1 (HSV-1) RNA labeled with with [methyl-3H] methionine at various times during the infectious cycle and purified by hybridization to viral DNA was analyzed for the presence of methylated nucleotides. The data indicate the following. (i) RNA labeled from 0 to 14 h postinfection and accumulating in the cytoplasm contained internal base-methylated nucleotides and terminal oligonucleotides consistent with the structure 7mG(5')ppp-(5')XmpYmpNp. Similar methylated nucleotides and oligonucleotides were also found in viral RNA accumulating in the cytoplasm of cells treated with cycloheximide from the time of infection. Previous studies (M. Kozak and B. Roizman, 1974) have shown that, whereas the RNA accumulating in the 14-h infected cells contains all of the sequences functioning as mRNA throughout infection, the RNA accumulating in the cytoplasm of cycloheximide-treated cells is associated with polyribosomes synthesizing the earliest (alpha) group of polypeptides specified by the virus. (ii) Cytoplasmic viral RNA from cells labeled 11 to 14 h postinfection as well as the total adenylated RNA in the cytoplasm and polyribosomes labeled in the same fashion contained the terminal oligonucleotide but not the internal base-methylated nucleotide."}
{"id": "PMID:186636", "title": "Genetic evidence for a product of the Fv-1 locus that transfers resistance to mouse leukemia viruses.", "content": "Extracts of mouse cells have been shown to transfer to N- or B-trophic host range types of mouse leukemia viruses. The genetic specificity of the inhibition was tested in two ways: (i) by correlating the Fv-1 genotype of a number of mouse strains with the restriction-transferring activity of extracts of the respective embryo cell cultures, and (ii) by correlating the Fv-1 genotype of BLC3F2 (C57BL/6 female [Fv-1bb] by C3H male [Fv-1nn] parental strains) mouse embryos, which segregate the Fv-1 alleles in a 12:1 ratio, with the inhibitor activity of extracts of the cells from each embryo. Five independent matings, totaling 45 individual embryos, were tested. Each embryo was cultured, and the Fv-1 genotype was determined independently by titration of N- and B-tropic viruses; the extracts of replicate secondary cultures were tested for their effect on infection of permissive cells by N- and B-tropic viruses. The specific-restriction-transferring activity of the embryos was found to segregate with the appropriate Fv-1 genotype. These res-lts confirm the suggestion that the inhibitor of the leukemia virus host range types in the cellular extracts is a product of the Fv-1 locus.", "contents": "Genetic evidence for a product of the Fv-1 locus that transfers resistance to mouse leukemia viruses. Extracts of mouse cells have been shown to transfer to N- or B-trophic host range types of mouse leukemia viruses. The genetic specificity of the inhibition was tested in two ways: (i) by correlating the Fv-1 genotype of a number of mouse strains with the restriction-transferring activity of extracts of the respective embryo cell cultures, and (ii) by correlating the Fv-1 genotype of BLC3F2 (C57BL/6 female [Fv-1bb] by C3H male [Fv-1nn] parental strains) mouse embryos, which segregate the Fv-1 alleles in a 12:1 ratio, with the inhibitor activity of extracts of the cells from each embryo. Five independent matings, totaling 45 individual embryos, were tested. Each embryo was cultured, and the Fv-1 genotype was determined independently by titration of N- and B-tropic viruses; the extracts of replicate secondary cultures were tested for their effect on infection of permissive cells by N- and B-tropic viruses. The specific-restriction-transferring activity of the embryos was found to segregate with the appropriate Fv-1 genotype. These res-lts confirm the suggestion that the inhibitor of the leukemia virus host range types in the cellular extracts is a product of the Fv-1 locus."}
{"id": "PMID:186637", "title": "Effect of hypertonic medium on protein synthesis of Mahoney and LSc poliovirus.", "content": "The initiation of synthesis of Mahoney virus protein is more sensitive to high osmolarity than initiation of synthesis of LSc virus protein. Production of Mahoney virus protein appears to be only slightly more resistant to high osmolarity than synthesis of HeLa-Rhino cell protein.", "contents": "Effect of hypertonic medium on protein synthesis of Mahoney and LSc poliovirus. The initiation of synthesis of Mahoney virus protein is more sensitive to high osmolarity than initiation of synthesis of LSc virus protein. Production of Mahoney virus protein appears to be only slightly more resistant to high osmolarity than synthesis of HeLa-Rhino cell protein."}
{"id": "PMID:186638", "title": "Analysis of structural polypeptides of purified human cytomegalovirus.", "content": "Human cytomegalovirus strain C87 was purified by the following procedures. (i) Extracellular virus was concentrated by centrifugation at 100,000 X g for 90 min and passed through a Bio-Rad Bio-Gel A-15m column. Most of the virus was recovered in the void volume. (ii) After two consecutive isopycnic potassium tartrate gradient centrifugations (20 to 50%), coinciding peaks of plaque titer, protein, and radioactivity were found at a density of from 1.20 to 1.21 g/cm3. To characterize the structural polypeptides of human cytomegalovirus and to establish relative purification criteria, virus was purified from two mixtures: (i) [35S]methionine-labeled extracellular virus mixed with an equal volume of unlabeled normal culture fluid; (ii) unlabeled extracellular virus mixed with an equal volume of [357a1methionine-labeled normal culture fluid. The extent of purification, as judged by the ratio of cellular to viral radioactivity, was 39-fold; i.e. about 2.5% of the protein in the purified virus preparation could be accounted for by host protein contamination. Electrophoresis of purified [35S]methionine-labeled virus on a polyacrylamide gel slab showed that there were at least 33 viral structural polypeptides (VPs), and their molecular weights ranged from 11,000 to 290,000. Autoradiograms obtained from electropherograms of purified [14C]glucosamine labeled virus showed six bands. Four of these were so broad that several VPs corresponded to each of the glycosylated bands. When heavy (two fractions close to 1.21 g/cm3) and light (two fractions close to 1.20 g/cm3) fractions of the PFU peak from the second potassium tartrate gradient were analyzed separately, the number of polypeptides observed was the same, but the relative amounts of some polypeptides differed. The major polypeptide, VP17, was found in greater amounts in the heavy fraction (35%) than in the light fraction (22%). The amount of DNA as a percentage of the weight of protein was 2% for the light fraction and 1% for the heavy fraction.", "contents": "Analysis of structural polypeptides of purified human cytomegalovirus. Human cytomegalovirus strain C87 was purified by the following procedures. (i) Extracellular virus was concentrated by centrifugation at 100,000 X g for 90 min and passed through a Bio-Rad Bio-Gel A-15m column. Most of the virus was recovered in the void volume. (ii) After two consecutive isopycnic potassium tartrate gradient centrifugations (20 to 50%), coinciding peaks of plaque titer, protein, and radioactivity were found at a density of from 1.20 to 1.21 g/cm3. To characterize the structural polypeptides of human cytomegalovirus and to establish relative purification criteria, virus was purified from two mixtures: (i) [35S]methionine-labeled extracellular virus mixed with an equal volume of unlabeled normal culture fluid; (ii) unlabeled extracellular virus mixed with an equal volume of [357a1methionine-labeled normal culture fluid. The extent of purification, as judged by the ratio of cellular to viral radioactivity, was 39-fold; i.e. about 2.5% of the protein in the purified virus preparation could be accounted for by host protein contamination. Electrophoresis of purified [35S]methionine-labeled virus on a polyacrylamide gel slab showed that there were at least 33 viral structural polypeptides (VPs), and their molecular weights ranged from 11,000 to 290,000. Autoradiograms obtained from electropherograms of purified [14C]glucosamine labeled virus showed six bands. Four of these were so broad that several VPs corresponded to each of the glycosylated bands. When heavy (two fractions close to 1.21 g/cm3) and light (two fractions close to 1.20 g/cm3) fractions of the PFU peak from the second potassium tartrate gradient were analyzed separately, the number of polypeptides observed was the same, but the relative amounts of some polypeptides differed. The major polypeptide, VP17, was found in greater amounts in the heavy fraction (35%) than in the light fraction (22%). The amount of DNA as a percentage of the weight of protein was 2% for the light fraction and 1% for the heavy fraction."}
{"id": "PMID:186639", "title": "Association of vesicular stomatitis virus proteins with HeLa cell membranes and released virus.", "content": "The association of vesicular stomatitis virus proteins with intracellular and plasma membranes was examined by pulse and pulse-chase labeling of virus-infected HeLa cells with [35S]methionine and separation of cell homogenates into three major membrane fractions in discontinuous sucrose gradients. The glycoprotein G was primarily associated with rough endoplasmic reticulum-like membranes after short radioactive pulses (2 to 4 min) but accumulated in the plasma membrane-enriched fraction and the smooth internal membrane fraction with longer pulse or chase periods. The nucleocapsid protein N and the matrix protein M accumulated in the rough endoplasmic reticulum and plasma membrane-like fractions but not in the smooth internal membrane fraction. Only a fraction (35 to 40%) of the viral protein synthesized during a short pulse in the mid-cycle of infection was apparently utilized in released virus. The newly synthesized virus proteins first appeared in released virus in the order: M, N and L, and G.", "contents": "Association of vesicular stomatitis virus proteins with HeLa cell membranes and released virus. The association of vesicular stomatitis virus proteins with intracellular and plasma membranes was examined by pulse and pulse-chase labeling of virus-infected HeLa cells with [35S]methionine and separation of cell homogenates into three major membrane fractions in discontinuous sucrose gradients. The glycoprotein G was primarily associated with rough endoplasmic reticulum-like membranes after short radioactive pulses (2 to 4 min) but accumulated in the plasma membrane-enriched fraction and the smooth internal membrane fraction with longer pulse or chase periods. The nucleocapsid protein N and the matrix protein M accumulated in the rough endoplasmic reticulum and plasma membrane-like fractions but not in the smooth internal membrane fraction. Only a fraction (35 to 40%) of the viral protein synthesized during a short pulse in the mid-cycle of infection was apparently utilized in released virus. The newly synthesized virus proteins first appeared in released virus in the order: M, N and L, and G."}
{"id": "PMID:186640", "title": "Glycosylation of vesicular stomatitis virus glycoprotein in virus-infected HeLa cells.", "content": "Glycosylation of the envelope glycoprotein of vesicular stomatitis virus was examined using virus-infected HeLa cells that were pulse-labeled with radioactive sugar precursors. The intracellular sites of glycosylation and the stepwise elongation of the carbohydrate side chains of the G protein were monitored by membrane fractionation and gel filtration of Pronase-digested glycopeptides. The results with short pulses of sugar label (5 to 10 mtein linkage (glucosamine and mannose) are added to G which was associated with the rough endoplasmic reticulum-enriched membrane fraction, whereas the more distal sugars (galactose, sialic acid, fucose, and possibly more glucosamine) are added in the light-density internal membrane fraction. Accumulation of mature G was observed in the plasma membrane-enriched fraction. The gel filtration studies indicated that the initial glycosylation event may be the en bloc addition of a mannose and glucosamine oligomer, followed by the stepwise addition of the more distal sugars.", "contents": "Glycosylation of vesicular stomatitis virus glycoprotein in virus-infected HeLa cells. Glycosylation of the envelope glycoprotein of vesicular stomatitis virus was examined using virus-infected HeLa cells that were pulse-labeled with radioactive sugar precursors. The intracellular sites of glycosylation and the stepwise elongation of the carbohydrate side chains of the G protein were monitored by membrane fractionation and gel filtration of Pronase-digested glycopeptides. The results with short pulses of sugar label (5 to 10 mtein linkage (glucosamine and mannose) are added to G which was associated with the rough endoplasmic reticulum-enriched membrane fraction, whereas the more distal sugars (galactose, sialic acid, fucose, and possibly more glucosamine) are added in the light-density internal membrane fraction. Accumulation of mature G was observed in the plasma membrane-enriched fraction. The gel filtration studies indicated that the initial glycosylation event may be the en bloc addition of a mannose and glucosamine oligomer, followed by the stepwise addition of the more distal sugars."}
{"id": "PMID:186641", "title": "Asymmetric distribution of phosphatidylethanolamine in the membrane of vesicular stomatitis virus.", "content": "The membrane-impermeable reagent trinitrobenzenesulfonate has been shown to react only with the surface components of vesicular stomatitis virus (VSV) membranes. When the amount of phosphatidylethanolamine (PE) available to modification by trinitrobenzenesulfonate in intact virions was determined, it was found that 36% of the total membrane PE was converted to the trinitrophenyl derivative. The same proportion of the total membrane PE was reactive after removal of the surface glycoprotein by trypsin digestion, but disruption of the virus membrane by sonication rendered all of the PE reactive. These results indicate that PE is asymmetrically distributed in the VSV membrane; 36% is present in the outer lipid leaflet, whereas 64% is found on the inner layer.", "contents": "Asymmetric distribution of phosphatidylethanolamine in the membrane of vesicular stomatitis virus. The membrane-impermeable reagent trinitrobenzenesulfonate has been shown to react only with the surface components of vesicular stomatitis virus (VSV) membranes. When the amount of phosphatidylethanolamine (PE) available to modification by trinitrobenzenesulfonate in intact virions was determined, it was found that 36% of the total membrane PE was converted to the trinitrophenyl derivative. The same proportion of the total membrane PE was reactive after removal of the surface glycoprotein by trypsin digestion, but disruption of the virus membrane by sonication rendered all of the PE reactive. These results indicate that PE is asymmetrically distributed in the VSV membrane; 36% is present in the outer lipid leaflet, whereas 64% is found on the inner layer."}
{"id": "PMID:186642", "title": "Ultrastructural studies of hepatitis A virus by electron microscopy.", "content": "Well-defined, core-like structures were visualized in hepatitis A virus particles by a modified microelectron microscopy technique.", "contents": "Ultrastructural studies of hepatitis A virus by electron microscopy. Well-defined, core-like structures were visualized in hepatitis A virus particles by a modified microelectron microscopy technique."}
{"id": "PMID:186655", "title": "In vitro studies on the mechanism of acquired resistance to tuberculous infection. II. The effects of the culture supernatants of specifically stimulated-sensitized lymphocytes on the growth of tubercle bacilli within macrophages.", "content": "Immune lymph node cells were obtained from mice immunized with bovine gamma globulin (BGG) in complete Freund's adjuvant or allogeneic MH134 tumor cells. They showed the capacity of conferring bactericidal activity on macrophages infected with Mycobacterium tuberculosis, H37Rv, when they were incubated on macrophage monolayers together with the corresponding antigen, i.e., BGG or solubilized cellular antigen of the tumor cells. However, such capacity was lower than that of tubercle bacilli-immune lymph node cells. Culture supernatants were harvested after incubation of tubercle bacilli-immune, BGG-immune or allogeneic tumor-immune lymph node cells with the corresponding antigen for 24 hr. Macrophages were altered so as to suppress intracellular bacillary growth when macrophage monolayers were exposed to the supernatants for more than 2 days. When normal lymph node cells were incubated on normal macrophage monolayers together with a mitogen such as PHA or concanavalin A, growth of tubercle bacilli within the macrophages was slightly but difinitely suppressed. The mechanism of elicitation of cellular immunity to the infection with tubercle bacilli is discussed on the basis of results presented in this and the preceding paper.", "contents": "In vitro studies on the mechanism of acquired resistance to tuberculous infection. II. The effects of the culture supernatants of specifically stimulated-sensitized lymphocytes on the growth of tubercle bacilli within macrophages. Immune lymph node cells were obtained from mice immunized with bovine gamma globulin (BGG) in complete Freund's adjuvant or allogeneic MH134 tumor cells. They showed the capacity of conferring bactericidal activity on macrophages infected with Mycobacterium tuberculosis, H37Rv, when they were incubated on macrophage monolayers together with the corresponding antigen, i.e., BGG or solubilized cellular antigen of the tumor cells. However, such capacity was lower than that of tubercle bacilli-immune lymph node cells. Culture supernatants were harvested after incubation of tubercle bacilli-immune, BGG-immune or allogeneic tumor-immune lymph node cells with the corresponding antigen for 24 hr. Macrophages were altered so as to suppress intracellular bacillary growth when macrophage monolayers were exposed to the supernatants for more than 2 days. When normal lymph node cells were incubated on normal macrophage monolayers together with a mitogen such as PHA or concanavalin A, growth of tubercle bacilli within the macrophages was slightly but difinitely suppressed. The mechanism of elicitation of cellular immunity to the infection with tubercle bacilli is discussed on the basis of results presented in this and the preceding paper."}
{"id": "PMID:186656", "title": "Immune response against hamster erythrocytes in the low-responder mouse strains. XI. Strain difference in the effects of various microbial adjuvants.", "content": "Enhancing and suppressing effects of microbial adjuvants were studied in female mice of the C3H/He, AKR and SL strains. Propionibacterium acnes, Bordetella pertussis, BCG and yeast cell wall (YCW) were chosen as adjuvants. As antigens, we chose hamster erythrocytes (HRBC) which proved to be a weak antigen for mice. Adjuvants were given on day --7, day 0 or day 3, and HRBC were injected on day 0. The results were as follows. 1) P. acnes facilitated IgM and IgG antibody production in AKR mice and suppressed IgM antibody production in SL mice, when given on day --7. When P. acnes was given on day 0, they suppressed IgM antibody production in all of the strains used. 2) When B. pertussis was given on day 0, it exhibited enhancing effects on IgG antibody production in all of the strains and a suppressing effect on IgM antibody production in SL mice. 3) BCG suppressed IgM antibody production in all strains when given on day 0. 4) YCW showed no influence on antibody production in any combination used in this work. 5) SL mice were very sensitive to suppressing effects by adjuvants. Strain differences in the expression of enhancing and suppressing effects by adjuvants appear to be under some control independent of antigen-specific immune response genes.", "contents": "Immune response against hamster erythrocytes in the low-responder mouse strains. XI. Strain difference in the effects of various microbial adjuvants. Enhancing and suppressing effects of microbial adjuvants were studied in female mice of the C3H/He, AKR and SL strains. Propionibacterium acnes, Bordetella pertussis, BCG and yeast cell wall (YCW) were chosen as adjuvants. As antigens, we chose hamster erythrocytes (HRBC) which proved to be a weak antigen for mice. Adjuvants were given on day --7, day 0 or day 3, and HRBC were injected on day 0. The results were as follows. 1) P. acnes facilitated IgM and IgG antibody production in AKR mice and suppressed IgM antibody production in SL mice, when given on day --7. When P. acnes was given on day 0, they suppressed IgM antibody production in all of the strains used. 2) When B. pertussis was given on day 0, it exhibited enhancing effects on IgG antibody production in all of the strains and a suppressing effect on IgM antibody production in SL mice. 3) BCG suppressed IgM antibody production in all strains when given on day 0. 4) YCW showed no influence on antibody production in any combination used in this work. 5) SL mice were very sensitive to suppressing effects by adjuvants. Strain differences in the expression of enhancing and suppressing effects by adjuvants appear to be under some control independent of antigen-specific immune response genes."}
{"id": "PMID:186657", "title": "Persistent high numbers of Clostridium perfringens in the intestines of Japanese aged adults.", "content": "TSN agar was applicable for enumeration of Clostridium perfringens in fecal samples of adults but not in those of infants. It was demonstrated using TSN agar that some healthy aged adults had persistently carried C. perfringens at levels ranging from 10(7) to 10(9), while some others ranged from 10(3) to 10(6) per ml volume of fecal sample although all of these adults had the same diets. In the test for agglutinability of isolates of C. perfringens collected from two elderly adults, a younger adult and a baby, it was demonstated that most of the isolates obtained from an aged adult of high levels for 19 months belonged the same serotype, while rapid alteration of serotypes could be observed in three other persons with high or low levels. In spite of as many as 10(9) C. perfringens per ml of feces, no trace of a-toxin could be detected in the fecal samples. In in vitro tests, fecal suspension suppressed the production of a-toxin although it allowed the organism to grow sufficiently.", "contents": "Persistent high numbers of Clostridium perfringens in the intestines of Japanese aged adults. TSN agar was applicable for enumeration of Clostridium perfringens in fecal samples of adults but not in those of infants. It was demonstrated using TSN agar that some healthy aged adults had persistently carried C. perfringens at levels ranging from 10(7) to 10(9), while some others ranged from 10(3) to 10(6) per ml volume of fecal sample although all of these adults had the same diets. In the test for agglutinability of isolates of C. perfringens collected from two elderly adults, a younger adult and a baby, it was demonstated that most of the isolates obtained from an aged adult of high levels for 19 months belonged the same serotype, while rapid alteration of serotypes could be observed in three other persons with high or low levels. In spite of as many as 10(9) C. perfringens per ml of feces, no trace of a-toxin could be detected in the fecal samples. In in vitro tests, fecal suspension suppressed the production of a-toxin although it allowed the organism to grow sufficiently."}
{"id": "PMID:186659", "title": "Rapid protein uptake and digestion in proximal tubule lysosomes.", "content": "The aim of the present study was to determine the initial time course for the handling of protein by the proximal tubule cells in rat kidney, using 125I-labeled cytochrome C as a tracer. The uptake of the protein was followed by electron microscope autoradiography in kidneys from rats fixed by perfusion after i.v. injection of cytochrome C. Protein degradation was studied by incubating cortical slices, taken from rats, injected with the same label, and measuring the release of trichloroacetic acid (TCA)-soluble radioactivity from the slices. It was shown by autoradiography that lysosomes in proximal tubule cells start to accumulate labeled cytochrome C within 3 min after injection of the protein, and that the concentration of label in lysosomes increases during the first 30 min after injection, whereas it decreases in endocytic vacuoles. The catabolism of protein as measured in cortical slices began within 13 min after the i.v. injection. Other experiments showed that the accumulation of cytochrome C in the kidneys is very fast. The maximum accumulation, 37% of the injected dose, was reached seven minutes after injection. The results show that protein uptake in proximal tubule cells, transport into lysosomes and the digestion of protein is a more rapid process than previously reported in ultrastructural studies.", "contents": "Rapid protein uptake and digestion in proximal tubule lysosomes. The aim of the present study was to determine the initial time course for the handling of protein by the proximal tubule cells in rat kidney, using 125I-labeled cytochrome C as a tracer. The uptake of the protein was followed by electron microscope autoradiography in kidneys from rats fixed by perfusion after i.v. injection of cytochrome C. Protein degradation was studied by incubating cortical slices, taken from rats, injected with the same label, and measuring the release of trichloroacetic acid (TCA)-soluble radioactivity from the slices. It was shown by autoradiography that lysosomes in proximal tubule cells start to accumulate labeled cytochrome C within 3 min after injection of the protein, and that the concentration of label in lysosomes increases during the first 30 min after injection, whereas it decreases in endocytic vacuoles. The catabolism of protein as measured in cortical slices began within 13 min after the i.v. injection. Other experiments showed that the accumulation of cytochrome C in the kidneys is very fast. The maximum accumulation, 37% of the injected dose, was reached seven minutes after injection. The results show that protein uptake in proximal tubule cells, transport into lysosomes and the digestion of protein is a more rapid process than previously reported in ultrastructural studies."}
{"id": "PMID:186660", "title": "Intracellular collagen fibrils in prolapsed (\"floppy\") human atrioventricular valves.", "content": "Ultrastructural study of prolapsed atrioventricular valves from five patients, one of whom also had the Marfan syndrome, disclosed granular cells that were characterized by numerous membrane-bound, electron-dense inclusions resembling those in the Hurler syndrome. Collagen fibrils were present within some of these inclusions. The intracellular collagen deposits may form as a consequence of abnormal interactions between newly secreted collagen and acid mucopolysaccharides.", "contents": "Intracellular collagen fibrils in prolapsed (\"floppy\") human atrioventricular valves. Ultrastructural study of prolapsed atrioventricular valves from five patients, one of whom also had the Marfan syndrome, disclosed granular cells that were characterized by numerous membrane-bound, electron-dense inclusions resembling those in the Hurler syndrome. Collagen fibrils were present within some of these inclusions. The intracellular collagen deposits may form as a consequence of abnormal interactions between newly secreted collagen and acid mucopolysaccharides."}
{"id": "PMID:186661", "title": "Pathogenesis of visna. II. Effect of immunosuppression upon early central nervous system lesions.", "content": "It was hypothesized that the lesions of visna might represent an immunopathologic process. To test this hypothesis, a 1-month schedule of immunosuppressive treatment was devised, using horse anti-sheep thymocyte serum. In Hampshire sheep, this regime was shown to protect against experimental allergic encephalomyelitis, to inhibit development of tuberculin hypersensitivity, to retard rejection of skin homografts by 3 weeks, and to markedly reduce the number and mitogenic responsiveness of peripheral blood lymphocytes. Two groups of Icelandic sheep received intracerebral inoculations of visna virus, and one group was treated with horse antisheep thymocyte serum supplemented by a short terminal course of cyclophosphamide. Central nervous system lesions were seen in only one of eight suppressed animals at sacrifice 25 days after infection, whereas definite lesions were present in eight of eight infected control animals. The frequency of central nervous system virus isolation was similar in the two groups, indicating that treatment suppressed the cellular proliferative response without preventing the central nervous system phase of infection. Sheep receiving horse antisheep thymocyte serum had a reduced number of virus isolations from peripheral lymphoid tissue, presumably reflecting the lympholytic effect of treatment. These observations are consistent with the immunopathologic hypothesis and suggest several different ways in which suppression could modify the immune response to visna virus.", "contents": "Pathogenesis of visna. II. Effect of immunosuppression upon early central nervous system lesions. It was hypothesized that the lesions of visna might represent an immunopathologic process. To test this hypothesis, a 1-month schedule of immunosuppressive treatment was devised, using horse anti-sheep thymocyte serum. In Hampshire sheep, this regime was shown to protect against experimental allergic encephalomyelitis, to inhibit development of tuberculin hypersensitivity, to retard rejection of skin homografts by 3 weeks, and to markedly reduce the number and mitogenic responsiveness of peripheral blood lymphocytes. Two groups of Icelandic sheep received intracerebral inoculations of visna virus, and one group was treated with horse antisheep thymocyte serum supplemented by a short terminal course of cyclophosphamide. Central nervous system lesions were seen in only one of eight suppressed animals at sacrifice 25 days after infection, whereas definite lesions were present in eight of eight infected control animals. The frequency of central nervous system virus isolation was similar in the two groups, indicating that treatment suppressed the cellular proliferative response without preventing the central nervous system phase of infection. Sheep receiving horse antisheep thymocyte serum had a reduced number of virus isolations from peripheral lymphoid tissue, presumably reflecting the lympholytic effect of treatment. These observations are consistent with the immunopathologic hypothesis and suggest several different ways in which suppression could modify the immune response to visna virus."}
{"id": "PMID:186662", "title": "Pathogenesis of visna. III. Immune responses to central nervous system antigens in experimental allergic encephalomyelitis and visna.", "content": "Experimental allergic encephalomyelitis (EAE) was induced in sheep in pursuit of the hypothesis that an immune response against central nervous system antigens might play a role in the pathogenesis of visna. Nine to 12 days after sensitization with whole sheep brain and complete Freund's adjuvant, approximately 50% of sheep developed a fulminating lethal form of EAE. Following a second sensitization, another 20% of animals developed EAE whereas a residual 30% failed to develop any signs or histologic evidence of disease. A histologic comparison of EAE and visna indicated considerable similarity in the nature of the pathologic process. However, the distribution of lesions was quite different, suggesting cellular responses to two different antigens, Cell-mediated immunity to myelin basic protein, as measured by lymphocyte blast transformation, was minimally elevated in sheep sensitized with whole brain suspension in complete Freund's adjuvant, whereas no response could be detected in visna-infected sheep. Complement-fixing antibody titers to basic protein and to a lipid antigen of brain, probably galactocerebroside, rose briskly after sensitization. In visna-infected sheep, on the other hand, there was no increase in either antibody. A large proportion of both Hampshire and Icelandic sheep had low levels of complement-fixing antibody to central nervous system antigens prior to induction of EAE or infection with visna virus. The origin of this antibody is undetermined, but it appeared to have no effect on the course of either disease. Immunosuppression of sheep with antilymphoid serum prevented induction of EAE. Acute EAE was, thus, successfully induced in sheep and used as a model to measure immune responses to central nervous system antigens and as an index of immunosuppression. However, these comparative studies did not provide any evidence for the role of an autoimmune response, to the two central nervous system antigens tested, in the pathogenesis of visna.", "contents": "Pathogenesis of visna. III. Immune responses to central nervous system antigens in experimental allergic encephalomyelitis and visna. Experimental allergic encephalomyelitis (EAE) was induced in sheep in pursuit of the hypothesis that an immune response against central nervous system antigens might play a role in the pathogenesis of visna. Nine to 12 days after sensitization with whole sheep brain and complete Freund's adjuvant, approximately 50% of sheep developed a fulminating lethal form of EAE. Following a second sensitization, another 20% of animals developed EAE whereas a residual 30% failed to develop any signs or histologic evidence of disease. A histologic comparison of EAE and visna indicated considerable similarity in the nature of the pathologic process. However, the distribution of lesions was quite different, suggesting cellular responses to two different antigens, Cell-mediated immunity to myelin basic protein, as measured by lymphocyte blast transformation, was minimally elevated in sheep sensitized with whole brain suspension in complete Freund's adjuvant, whereas no response could be detected in visna-infected sheep. Complement-fixing antibody titers to basic protein and to a lipid antigen of brain, probably galactocerebroside, rose briskly after sensitization. In visna-infected sheep, on the other hand, there was no increase in either antibody. A large proportion of both Hampshire and Icelandic sheep had low levels of complement-fixing antibody to central nervous system antigens prior to induction of EAE or infection with visna virus. The origin of this antibody is undetermined, but it appeared to have no effect on the course of either disease. Immunosuppression of sheep with antilymphoid serum prevented induction of EAE. Acute EAE was, thus, successfully induced in sheep and used as a model to measure immune responses to central nervous system antigens and as an index of immunosuppression. However, these comparative studies did not provide any evidence for the role of an autoimmune response, to the two central nervous system antigens tested, in the pathogenesis of visna."}
{"id": "PMID:186663", "title": "In vivo assembly and maturation of vesicular stomatitis virus.", "content": "Previous studies on vesicular stomatitis virus (VSV) maturation in infected cells have utilized in vitro cell cultures. The present study is, to our knowledge, the first in vivo analysis of VSV-cell interaction in the central nervous system of weaning outbred Swiss mice. Intracerebral inoculation of wild-type VSV resulted in rapid viral replication in brain and spinal cord. By immunoflourescence, viral antigens were first seen in ependymal cells of brain and spinal cord and soon thereafter in surrounding neurons. The large anterior horn neurons of spinal cord appeared to be in the most heavily infected. Ultrastructurally, VSV-neuron interaction evolved in three phases. The first phase consisted of viral entry into the cell by fusion and viropexis. The second phase was characterized by nucleocapsid accumulation and resulted in the appearance of large cytoplasmic inclusions. The third phase was maturation and release from the infected cell and was accomplished by viral budding from plasma membranes. Degenerative changes in infected neurons were generally absent. Cells in the area of the central canal seemed to present a different pattern of virus-cell interaction especially at the level of maturation and release. Some of these cells in advanced stages of degeneration showed viral particles free in nucleocapsid material with no virus-membrane association. Viral budding was not observed and, because these cells do eventually die, it is possible that virus was released in the intercellular space at the moment of cellular disruption. These results suggest that VSV-cell interactions may vary depending upon the nature of the infected cells.", "contents": "In vivo assembly and maturation of vesicular stomatitis virus. Previous studies on vesicular stomatitis virus (VSV) maturation in infected cells have utilized in vitro cell cultures. The present study is, to our knowledge, the first in vivo analysis of VSV-cell interaction in the central nervous system of weaning outbred Swiss mice. Intracerebral inoculation of wild-type VSV resulted in rapid viral replication in brain and spinal cord. By immunoflourescence, viral antigens were first seen in ependymal cells of brain and spinal cord and soon thereafter in surrounding neurons. The large anterior horn neurons of spinal cord appeared to be in the most heavily infected. Ultrastructurally, VSV-neuron interaction evolved in three phases. The first phase consisted of viral entry into the cell by fusion and viropexis. The second phase was characterized by nucleocapsid accumulation and resulted in the appearance of large cytoplasmic inclusions. The third phase was maturation and release from the infected cell and was accomplished by viral budding from plasma membranes. Degenerative changes in infected neurons were generally absent. Cells in the area of the central canal seemed to present a different pattern of virus-cell interaction especially at the level of maturation and release. Some of these cells in advanced stages of degeneration showed viral particles free in nucleocapsid material with no virus-membrane association. Viral budding was not observed and, because these cells do eventually die, it is possible that virus was released in the intercellular space at the moment of cellular disruption. These results suggest that VSV-cell interactions may vary depending upon the nature of the infected cells."}
{"id": "PMID:186664", "title": "The effect of changes in dietary sodium on lung and serum antiotensin-I-converting enzyme in the rat.", "content": "Three groups of rats were fed a sodium-deficient diet, a normal sodium diet, and a diet high in sodium for up to 8 weeks. Animals on a sodium-deficient diet had a significant decrease of serum sodium levels with a concomitant increase of renal renin granules. The reverse was true in rats on a high sodium diet whereas no significant changes in renin granulation were seen in rats fed a normal sodium diet. The changes in serum sodium levels and in number of renal renin granules were not associated with changes in lung or serum angiotensin-I-converting enzyme activity which did not vary significantly in any of the three groups of rats throughout the experiment. It is, therefore, suggested that such activity is independent of changes in sodium balance sufficient to affect the renal renin content.", "contents": "The effect of changes in dietary sodium on lung and serum antiotensin-I-converting enzyme in the rat. Three groups of rats were fed a sodium-deficient diet, a normal sodium diet, and a diet high in sodium for up to 8 weeks. Animals on a sodium-deficient diet had a significant decrease of serum sodium levels with a concomitant increase of renal renin granules. The reverse was true in rats on a high sodium diet whereas no significant changes in renin granulation were seen in rats fed a normal sodium diet. The changes in serum sodium levels and in number of renal renin granules were not associated with changes in lung or serum angiotensin-I-converting enzyme activity which did not vary significantly in any of the three groups of rats throughout the experiment. It is, therefore, suggested that such activity is independent of changes in sodium balance sufficient to affect the renal renin content."}
{"id": "PMID:186666", "title": "A study of adenosine 3'-5' cyclic monophosphate binding sites of human erythrocyte membranes using 8-azidoadenosine 3'-5' cyclic monophosphate, a photoaffinity probe.", "content": "An earlier report (1a) has shown the utility of 8-N3cAMP (8-azidoadenosine-3', 5'-cyclic monophosphate) as a photoaffinity probe for cAMP binding sites in human erythrocyte membranes. The increased resolution obtained using a linear-gradient SDS polyacrylamide gel system now shows that: 1) both cAMP and 8-N3cAMP stimulate the phosphorylation by [gamma-32P]-ATP of the same red cell membrane proteins; 2) the protein of approximately 48,000 molecular weight whose phosphorylation by [gamma-32P]-ATP is stimulated by cAMP and 8-N3cAMP migrates at a slower rate than the protein in the same molecular weight range which is heavily photolabeled with [32P]-8-N3cAMP;3) other cyclic nucleotide binding sites exist besides those initially reported; 4) the variation in the ratio of incorporation of [32P]-8-N3cAMP into the two highest affinity binding sites appears to be the result of a specific proteolysis of the larger protein.", "contents": "A study of adenosine 3'-5' cyclic monophosphate binding sites of human erythrocyte membranes using 8-azidoadenosine 3'-5' cyclic monophosphate, a photoaffinity probe. An earlier report (1a) has shown the utility of 8-N3cAMP (8-azidoadenosine-3', 5'-cyclic monophosphate) as a photoaffinity probe for cAMP binding sites in human erythrocyte membranes. The increased resolution obtained using a linear-gradient SDS polyacrylamide gel system now shows that: 1) both cAMP and 8-N3cAMP stimulate the phosphorylation by [gamma-32P]-ATP of the same red cell membrane proteins; 2) the protein of approximately 48,000 molecular weight whose phosphorylation by [gamma-32P]-ATP is stimulated by cAMP and 8-N3cAMP migrates at a slower rate than the protein in the same molecular weight range which is heavily photolabeled with [32P]-8-N3cAMP;3) other cyclic nucleotide binding sites exist besides those initially reported; 4) the variation in the ratio of incorporation of [32P]-8-N3cAMP into the two highest affinity binding sites appears to be the result of a specific proteolysis of the larger protein."}
{"id": "PMID:186668", "title": "Change in the stability of tendon collagen during ageing in the reptile, Calotes versicolor. A brief note.", "content": "Age related changes in the digestibility of tendon collagen of the garden lizard, Calotes versicolor, were traced using type I collagenase from Clostridium histolyticum. Collagen from older lizards showed less susceptibility for collagenase digestion than the younger lizards suggesting increased number of cross-linkages comparable with mammals.", "contents": "Change in the stability of tendon collagen during ageing in the reptile, Calotes versicolor. A brief note. Age related changes in the digestibility of tendon collagen of the garden lizard, Calotes versicolor, were traced using type I collagenase from Clostridium histolyticum. Collagen from older lizards showed less susceptibility for collagenase digestion than the younger lizards suggesting increased number of cross-linkages comparable with mammals."}
{"id": "PMID:186669", "title": "A system for measuring the noradrenaline receptor contribution to the flexor reflex.", "content": "A system is described for recording psoas muscle contractions in response to stimuli delivered to the sole of the foot of the acute spinalized unanaesthetized rat. Clonidine, an alpha adrenergic receptor agonist, caused a major increase in this flexor reflex amplitude. The increase was blocked by phenoxybenzamine at a dosage level of 20 mg/kg which did not, of itself, reduce flexor reflex amplitude. Older, larger rats responded significantly more forcefully to clonidine than did younger, smaller rats. However, these differences between rats of different size tended to disappear when the data were expressed in terms of 0/0 of original baseline amplitude. L-dopa, 75 mg/kg, increased the flexor reflex amplitude more so than did L(+)erythro dihydroxyphenylserine (DOPS) at twice the disage in rats pretreated with reserpine and nialamide. Other DOPS isomers were less effective, and L(-)threo DOPS was toxic. These results support the view that spinal noradrenaline receptors exist that increase the psoas flexor reflex. The advantages of the present system are twofold: first, the results may be quantitated; second, small amounts of potential central noradrenaline receptor agonists and antagonists may be tested for their effect on the flexor reflex using relatively few unanaesthetized rats.", "contents": "A system for measuring the noradrenaline receptor contribution to the flexor reflex. A system is described for recording psoas muscle contractions in response to stimuli delivered to the sole of the foot of the acute spinalized unanaesthetized rat. Clonidine, an alpha adrenergic receptor agonist, caused a major increase in this flexor reflex amplitude. The increase was blocked by phenoxybenzamine at a dosage level of 20 mg/kg which did not, of itself, reduce flexor reflex amplitude. Older, larger rats responded significantly more forcefully to clonidine than did younger, smaller rats. However, these differences between rats of different size tended to disappear when the data were expressed in terms of 0/0 of original baseline amplitude. L-dopa, 75 mg/kg, increased the flexor reflex amplitude more so than did L(+)erythro dihydroxyphenylserine (DOPS) at twice the disage in rats pretreated with reserpine and nialamide. Other DOPS isomers were less effective, and L(-)threo DOPS was toxic. These results support the view that spinal noradrenaline receptors exist that increase the psoas flexor reflex. The advantages of the present system are twofold: first, the results may be quantitated; second, small amounts of potential central noradrenaline receptor agonists and antagonists may be tested for their effect on the flexor reflex using relatively few unanaesthetized rats."}
{"id": "PMID:186670", "title": "Clinical significance of viral latency.", "content": "Evidence is accumulating to show that a number of viruses have the ability to adapt to man's defense mechanisms and survive in a latent state for what appears to be the life of the human host. Unfortunately, latent viral presence, which may appear clinically benign initally, may manifest itself later as severe and often fatal disease. Some members of the herpes virus family have latent potential and are discussed in detail. Clinical competence would suggest a thorough understanding of these late manifestations of occult viral presence.", "contents": "Clinical significance of viral latency. Evidence is accumulating to show that a number of viruses have the ability to adapt to man's defense mechanisms and survive in a latent state for what appears to be the life of the human host. Unfortunately, latent viral presence, which may appear clinically benign initally, may manifest itself later as severe and often fatal disease. Some members of the herpes virus family have latent potential and are discussed in detail. Clinical competence would suggest a thorough understanding of these late manifestations of occult viral presence."}
{"id": "PMID:186686", "title": "Effect of ethanol ingestion on choline phosphotransferase and phosphatidyl ethanolamine methyltransferase activities in liver microsomes.", "content": "The effect of ethanol ingestion on choline phosphotransferase and phosphatidyl ethanolamine methyltransferase activities, the two enzymes involved in phosphatidyl choline biosynthesis in liver microsomes, has been investigated. Female rats were fed a 5% ethanol-liquid diet containing amino acids, minerals, vitamins, with and without choline, for 2, 6 and 10 weeks. Control animals were pair-fed the same isocaloric diet with 5% sucrose with and without choline. Ethanol administration with or without dietary choline stimulated significantly (P less than 0.001) the specific activities of phosphatidyl ethanolamine methyltransferase in liver microsomes in the animals fed 5% ethanol for 2, 6, and 10 weeks, when compared to those control animals pair-fed the isocaloric diet with or without choline. Ethanol administration with or without dietary choline for 2 weeks stimulated significantly (P less than 0.02) the specific activities of choline phosphotransferase. The specific activities of phosphatidyl ethanolamine methyltransferase continued to increase in the liver microsomes from the animals in which dietary choline was omitted for 2, 6, and 10 weeks in the sucrose controls and alcohol-fed animals. Ethanol administration stimulates significantly (P less than 0.001) the phosphatidyl ethanolamine methyltransferase specific activities in liver microsomes of animals fed the liquid diet with dietary omission of choline and methionine for 2 weeks.", "contents": "Effect of ethanol ingestion on choline phosphotransferase and phosphatidyl ethanolamine methyltransferase activities in liver microsomes. The effect of ethanol ingestion on choline phosphotransferase and phosphatidyl ethanolamine methyltransferase activities, the two enzymes involved in phosphatidyl choline biosynthesis in liver microsomes, has been investigated. Female rats were fed a 5% ethanol-liquid diet containing amino acids, minerals, vitamins, with and without choline, for 2, 6 and 10 weeks. Control animals were pair-fed the same isocaloric diet with 5% sucrose with and without choline. Ethanol administration with or without dietary choline stimulated significantly (P less than 0.001) the specific activities of phosphatidyl ethanolamine methyltransferase in liver microsomes in the animals fed 5% ethanol for 2, 6, and 10 weeks, when compared to those control animals pair-fed the isocaloric diet with or without choline. Ethanol administration with or without dietary choline for 2 weeks stimulated significantly (P less than 0.02) the specific activities of choline phosphotransferase. The specific activities of phosphatidyl ethanolamine methyltransferase continued to increase in the liver microsomes from the animals in which dietary choline was omitted for 2, 6, and 10 weeks in the sucrose controls and alcohol-fed animals. Ethanol administration stimulates significantly (P less than 0.001) the phosphatidyl ethanolamine methyltransferase specific activities in liver microsomes of animals fed the liquid diet with dietary omission of choline and methionine for 2 weeks."}
{"id": "PMID:186687", "title": "The optimization of Porous glasses for immobilized enzyme (IME) systems.", "content": "Critical parameters involved in the selection of porous glass for use as support materials in the immobilization of biologically active materials are discussed. The importance of physical properties such as pore morphology, surface area and particle size relative to the final activity of the enzyme is shown using glucoamylase IME as a model system. The process of selection of specific materials with respect to the environmental conditions of the enzyme and the chemical durability of the support is considered, as are the mechanical properties required in the scale-up of an application.", "contents": "The optimization of Porous glasses for immobilized enzyme (IME) systems. Critical parameters involved in the selection of porous glass for use as support materials in the immobilization of biologically active materials are discussed. The importance of physical properties such as pore morphology, surface area and particle size relative to the final activity of the enzyme is shown using glucoamylase IME as a model system. The process of selection of specific materials with respect to the environmental conditions of the enzyme and the chemical durability of the support is considered, as are the mechanical properties required in the scale-up of an application."}
{"id": "PMID:186690", "title": "Physiologic significance of glucocorticoids and insulin in the regulation of hepatic gluconeogenesis during starvation in rats.", "content": "The physiologic significance of glucocorticoids and insulin in the regulation of hepatic gluconeogenesis was investigated during a 48-hr starvation period by studying the factors presumed to control the rate of glucose synthesis in the final gluconeogenetic pathway. Rats were used, in which glucorticoids were removed by adrenalectomy before starvation, and in which serum insulin was kept constant before and after food withdrawal by pre-feeding with a proteinfree diet. It was found that adrenalectomized rats at constantly low serum insulin levels responded to starvation as rapidly, and to the same degree, as intact control subjects (1) by a significant increase in plasma glucagon and, consequently, in hepatic cAMP concentration; (2) by a coordinate elevation of the activities of hepatic pyruvate carboxylase, P-enolpyruvate carboxykinase, and fructose-1,6-diphosphatase; (3) by systematic alterations in the concentration of effectors of gluconeogenetic key enzymes; (4) by a shifting of the cytoplasmic NAD system towards the reduced state; (5) by a decrease in the intrahepatic concentration of glycogenic precursor substrates. These results suggest that the hepatic gluconeogenic response to starvation with respect to the regulatory factors 1-5 occurs independently from changes in the concentration of plasma glucocorticoids and insulin. The crossing over of the gluconeogenetic intermediates between pyruvate and P-enolpyruvate (PEP), which was observed in intact but not in adrenalectomized rats, supports the assumption that during starvation, glucocorticoids enhance the rate of glucose production by the liver predominantly by permitting hepatic cAMP to stimulate the yet undefined mechanism, which has been demonstrated in the isolated perfused rat liver to control the substrate flow between pyruvate and PEP.", "contents": "Physiologic significance of glucocorticoids and insulin in the regulation of hepatic gluconeogenesis during starvation in rats. The physiologic significance of glucocorticoids and insulin in the regulation of hepatic gluconeogenesis was investigated during a 48-hr starvation period by studying the factors presumed to control the rate of glucose synthesis in the final gluconeogenetic pathway. Rats were used, in which glucorticoids were removed by adrenalectomy before starvation, and in which serum insulin was kept constant before and after food withdrawal by pre-feeding with a proteinfree diet. It was found that adrenalectomized rats at constantly low serum insulin levels responded to starvation as rapidly, and to the same degree, as intact control subjects (1) by a significant increase in plasma glucagon and, consequently, in hepatic cAMP concentration; (2) by a coordinate elevation of the activities of hepatic pyruvate carboxylase, P-enolpyruvate carboxykinase, and fructose-1,6-diphosphatase; (3) by systematic alterations in the concentration of effectors of gluconeogenetic key enzymes; (4) by a shifting of the cytoplasmic NAD system towards the reduced state; (5) by a decrease in the intrahepatic concentration of glycogenic precursor substrates. These results suggest that the hepatic gluconeogenic response to starvation with respect to the regulatory factors 1-5 occurs independently from changes in the concentration of plasma glucocorticoids and insulin. The crossing over of the gluconeogenetic intermediates between pyruvate and P-enolpyruvate (PEP), which was observed in intact but not in adrenalectomized rats, supports the assumption that during starvation, glucocorticoids enhance the rate of glucose production by the liver predominantly by permitting hepatic cAMP to stimulate the yet undefined mechanism, which has been demonstrated in the isolated perfused rat liver to control the substrate flow between pyruvate and PEP."}
{"id": "PMID:186691", "title": "Effect of acute uremia on triglyceride kinetics in the rat.", "content": "Plasma triglyceride (TG) levesl were elevated 24 hr after the production of acute uremia in rats. The effect of acute uremia on TG production rate was estimated by determining the rate of TG accumulation following Triton WR 1339 inhibition of lipoprotein removal, by measuring hepatic TG secretion rate during in situ liver perfusion, and by quantifying hepatocyte very low density lipoprotein content with the electron microscope. The results of all three of these approaches indicated that TG synthesis and secretion were decreased in acute uremia, suggesting that the associated increase in plasma TG levels had to result from a removal defect. This hypothesis was tested directly by injecting pre-labeled very low density lipoprotein TG into acutely uremic and control rats, and measuring its rate of disappearance from plasma. The t1/2 of removal in acutely uremic rats was found to be approximately twice that of control, confirming the hypothesis that the rise in plasma TG levels in acute uremia is due to a defect in removal of TG from plasma.", "contents": "Effect of acute uremia on triglyceride kinetics in the rat. Plasma triglyceride (TG) levesl were elevated 24 hr after the production of acute uremia in rats. The effect of acute uremia on TG production rate was estimated by determining the rate of TG accumulation following Triton WR 1339 inhibition of lipoprotein removal, by measuring hepatic TG secretion rate during in situ liver perfusion, and by quantifying hepatocyte very low density lipoprotein content with the electron microscope. The results of all three of these approaches indicated that TG synthesis and secretion were decreased in acute uremia, suggesting that the associated increase in plasma TG levels had to result from a removal defect. This hypothesis was tested directly by injecting pre-labeled very low density lipoprotein TG into acutely uremic and control rats, and measuring its rate of disappearance from plasma. The t1/2 of removal in acutely uremic rats was found to be approximately twice that of control, confirming the hypothesis that the rise in plasma TG levels in acute uremia is due to a defect in removal of TG from plasma."}
{"id": "PMID:186692", "title": "Sequential alterations in the hepatic content and metabolism of cyclic AMP and cyclic GMP induced by DL-ethionine: evidence for malignant transformation of liver with a sustained increase in cyclic AMP.", "content": "There is evidence than adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) may have antagonistic actions on cell growth, with cAMP inhibiting and cGMP stimulating this process. However, reductions in cAMP and increases in cGMP are not charactersitic of all neoplastic tissues. Thus, benign and malignant tissues from hepatoma-bearing rats exposed to the hepatic carcinogen DL-ethionine have elevated rather than depressed cAMP, compared to control liver, and parenteral administration of this drug increases hepatic cAMP within hours. In the present study, the effects of ethionine ingestion on the hepatic content and metabolism of both cAMP and cGMP were examined sequentially in rats at 2 and then 6 wk intervals, from the initiation of drug administration until the development of hepatomas. After 2 wk, cAMP content of quick-frozen liver from rats receiving ethionine (E) was significantly increased (826 +/- 91 pmole/g wet weight) above that of liver from pair-fed controls (C, 415 +/- 44), whether calculated by tissue wet weight, protein, or DNA content. In benign tissue from E, higher cAMP was still evident after in vitro incubations of slices with 2 mM 1-methyl-3-iso-butylxanthine (MIX) and was associated with enhanced adenylate cyclase and unchanged high or low Km cAMP-phosphodiesterase activities. These findings are compatible with accelerated cAMP generation in liver from E. Protein kinase activity ratios were significantly increased in frozen liver from E (0.52 +/- 0.04 versus 0.36 +/- 0.03 in C), and the percent glycogen synthetase in the I form was clearly reduced (19% +/- 2% in E versus 47% +/- 5% in c). incubation of hepatic slices from E or C with MIX and/or 10 muM glucagon further increased cAMP and protein kinase activity ratios, data which imply higher effective, as well as total, cellular cAMP in E. Changes in cAMP metabolism and action observed at 2 wk persisted throughout the 38-wk period of drug ingestion. Adenylate cyclase activity, cAMP content, and protein kinase activity ratios of ethionine-induced hepatomas exceeded those of both the surrounding liver from tumor-bearing rats and that of control liver, but alterations in these parameters were qualitatively similar in both tissues from E. By contrast, while cGMP in quick-frozen surrounding liver from tumor-bearing rats (36 +/- 4 pmole/g wet weight) did not differ from that of control liver (30 +/- 3), cGMP in the hepatomas was increased. This change was evident in both frozen tumor (89 +/- 10) and in tumor slices incubated in vitro with MIX (C, 90 +/- 11; surrounding liver, 85 +/- 10; hepatoma 231 +/- 29). These results indicate that malignant conversion can occur in liver with a sustained elevation of both total and effective cAMP during the premalignant phase. The increase in cGMP detected in ethionine-induced hepatomas could also be a key determinant of malignant transformation in the model, although premalignant changes in cGMP were not apparent.", "contents": "Sequential alterations in the hepatic content and metabolism of cyclic AMP and cyclic GMP induced by DL-ethionine: evidence for malignant transformation of liver with a sustained increase in cyclic AMP. There is evidence than adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) may have antagonistic actions on cell growth, with cAMP inhibiting and cGMP stimulating this process. However, reductions in cAMP and increases in cGMP are not charactersitic of all neoplastic tissues. Thus, benign and malignant tissues from hepatoma-bearing rats exposed to the hepatic carcinogen DL-ethionine have elevated rather than depressed cAMP, compared to control liver, and parenteral administration of this drug increases hepatic cAMP within hours. In the present study, the effects of ethionine ingestion on the hepatic content and metabolism of both cAMP and cGMP were examined sequentially in rats at 2 and then 6 wk intervals, from the initiation of drug administration until the development of hepatomas. After 2 wk, cAMP content of quick-frozen liver from rats receiving ethionine (E) was significantly increased (826 +/- 91 pmole/g wet weight) above that of liver from pair-fed controls (C, 415 +/- 44), whether calculated by tissue wet weight, protein, or DNA content. In benign tissue from E, higher cAMP was still evident after in vitro incubations of slices with 2 mM 1-methyl-3-iso-butylxanthine (MIX) and was associated with enhanced adenylate cyclase and unchanged high or low Km cAMP-phosphodiesterase activities. These findings are compatible with accelerated cAMP generation in liver from E. Protein kinase activity ratios were significantly increased in frozen liver from E (0.52 +/- 0.04 versus 0.36 +/- 0.03 in C), and the percent glycogen synthetase in the I form was clearly reduced (19% +/- 2% in E versus 47% +/- 5% in c). incubation of hepatic slices from E or C with MIX and/or 10 muM glucagon further increased cAMP and protein kinase activity ratios, data which imply higher effective, as well as total, cellular cAMP in E. Changes in cAMP metabolism and action observed at 2 wk persisted throughout the 38-wk period of drug ingestion. Adenylate cyclase activity, cAMP content, and protein kinase activity ratios of ethionine-induced hepatomas exceeded those of both the surrounding liver from tumor-bearing rats and that of control liver, but alterations in these parameters were qualitatively similar in both tissues from E. By contrast, while cGMP in quick-frozen surrounding liver from tumor-bearing rats (36 +/- 4 pmole/g wet weight) did not differ from that of control liver (30 +/- 3), cGMP in the hepatomas was increased. This change was evident in both frozen tumor (89 +/- 10) and in tumor slices incubated in vitro with MIX (C, 90 +/- 11; surrounding liver, 85 +/- 10; hepatoma 231 +/- 29). These results indicate that malignant conversion can occur in liver with a sustained elevation of both total and effective cAMP during the premalignant phase. The increase in cGMP detected in ethionine-induced hepatomas could also be a key determinant of malignant transformation in the model, although premalignant changes in cGMP were not apparent."}
{"id": "PMID:186694", "title": "Enzymic activities of cadmium- and zinc-tolerant strains of Klebsiella (Aerobacter) aerogenes growing in glucose-limited chemostats.", "content": "The activities of phosphatases and some enzymes of glucose metabolism were determined in K. aerogenes NCIB 418 and in two strains derived from it, resistant to 50 mug Cd2+ ml-1 and 16 mug Zn2+ ml-1 respectively, during growth at D = 0.38 h-1 in medium containing beta-glycerophosphate as sole phosphorus source and supplemented with Cd2+ and Zn2+, as appropriate, for the resistant strains. The pH-activity profiles of the phosphatases differed from strain to strain but all showed maximum activity at an acid pH and this activity was very much lower in the Zn2+-resistant strain than in the control and even lower in the Cd2+-resistant strain. Resistance to either metal was associated with decreased glucose-6-phosphate dehydrogenase activity and increased phosphoglucose isomerase activity, suggesting an increased flow of carbon through the Embden-Meyerhof pathway relative to the pentose phosphate pathway, but the efficiency of the conversion of glucose into biomass was largely unaffected. Glucose phosphoenolpyruvate phosphotransferase activity was also lower in the resistant strains.", "contents": "Enzymic activities of cadmium- and zinc-tolerant strains of Klebsiella (Aerobacter) aerogenes growing in glucose-limited chemostats. The activities of phosphatases and some enzymes of glucose metabolism were determined in K. aerogenes NCIB 418 and in two strains derived from it, resistant to 50 mug Cd2+ ml-1 and 16 mug Zn2+ ml-1 respectively, during growth at D = 0.38 h-1 in medium containing beta-glycerophosphate as sole phosphorus source and supplemented with Cd2+ and Zn2+, as appropriate, for the resistant strains. The pH-activity profiles of the phosphatases differed from strain to strain but all showed maximum activity at an acid pH and this activity was very much lower in the Zn2+-resistant strain than in the control and even lower in the Cd2+-resistant strain. Resistance to either metal was associated with decreased glucose-6-phosphate dehydrogenase activity and increased phosphoglucose isomerase activity, suggesting an increased flow of carbon through the Embden-Meyerhof pathway relative to the pentose phosphate pathway, but the efficiency of the conversion of glucose into biomass was largely unaffected. Glucose phosphoenolpyruvate phosphotransferase activity was also lower in the resistant strains."}
{"id": "PMID:186695", "title": "Malignant disease of the nasopharynx presenting as pain in the head and neck.", "content": "Two patients with an unusual pattern of pain in the head and face, who presented a diagnostic problem for one and four years respectively, subsequently proved to have a carcinoma of nasopharyngeal origin. The neurological complications of this condition are described.", "contents": "Malignant disease of the nasopharynx presenting as pain in the head and neck. Two patients with an unusual pattern of pain in the head and face, who presented a diagnostic problem for one and four years respectively, subsequently proved to have a carcinoma of nasopharyngeal origin. The neurological complications of this condition are described."}
{"id": "PMID:186696", "title": "Treatment with gentamicin monitored by serum antibiotic assay.", "content": "Gentamicin is very widely accepted as the most effective antibiotic for treatment of a number of serious Gram-negative infections, but one disadvantage associated with its use is the risk of toxicity particularly affecting the eighth nerve. An account is given of eight years' experience with this antibiotic in which obvious ototoxicity was avoided in hospitalized patients in whom gentamicin treatment was monitored by assay of the residual amounts of antibiotic present in the serum. The relationship between accumulation of gentamicin in patients with renal impairment and ototoxicity is discussed. Attention is drawn also to the presence of an increased risk of ototoxicity in patients, particularly the elderly, in whom mild-to-moderate degrees of renal impairment may be overlooked. In such patients modification of the frequency of the dose of gentamicin is necessary and a schedule of treatment based on the results of assay of residual serum levels of gentamicin is given.", "contents": "Treatment with gentamicin monitored by serum antibiotic assay. Gentamicin is very widely accepted as the most effective antibiotic for treatment of a number of serious Gram-negative infections, but one disadvantage associated with its use is the risk of toxicity particularly affecting the eighth nerve. An account is given of eight years' experience with this antibiotic in which obvious ototoxicity was avoided in hospitalized patients in whom gentamicin treatment was monitored by assay of the residual amounts of antibiotic present in the serum. The relationship between accumulation of gentamicin in patients with renal impairment and ototoxicity is discussed. Attention is drawn also to the presence of an increased risk of ototoxicity in patients, particularly the elderly, in whom mild-to-moderate degrees of renal impairment may be overlooked. In such patients modification of the frequency of the dose of gentamicin is necessary and a schedule of treatment based on the results of assay of residual serum levels of gentamicin is given."}
{"id": "PMID:186698", "title": "Multiple regulation of nucleoside catabolizing enzymes in Escherichia coli: effects of 3:5' cyclic AMP and CRP protein.", "content": "The regulation of the synthesis of nucleoside metabolizing enzymes has been studied in cya and crp mutant strains of Escherichia coli. The synthesis of the cyt-enzymes, cytidine deaminase and uridine phosphorylase regulated by the cytR gene product, is activated by the cAMP-CRP complex. On the other hand the synthesis of the deoenzymes: deoxyriboaldolase, thymidine phosphorylase, phosphodeoxyribomutase and purine nucleoside phosphorylase, appears to be increased if an active cAMP-CRP complex cannot be formed. It also seems that nucleosides serve as poor carbon sources for cya and crp mutants; this could not solely be explained by low levels of nucleoside metabolizing enzymes nor by a deficiency in nucleoside uptake. Addition of casamino acids stimulated the growth of cya and crp mutants, with nucleosides as carbon sources. When grown on glucose and casamino acids growth could be stimulated by adenine and hypoxanthine nucleosides; these results suggest an impaired nitrogen metabolism in cya and crp mutants.", "contents": "Multiple regulation of nucleoside catabolizing enzymes in Escherichia coli: effects of 3:5' cyclic AMP and CRP protein. The regulation of the synthesis of nucleoside metabolizing enzymes has been studied in cya and crp mutant strains of Escherichia coli. The synthesis of the cyt-enzymes, cytidine deaminase and uridine phosphorylase regulated by the cytR gene product, is activated by the cAMP-CRP complex. On the other hand the synthesis of the deoenzymes: deoxyriboaldolase, thymidine phosphorylase, phosphodeoxyribomutase and purine nucleoside phosphorylase, appears to be increased if an active cAMP-CRP complex cannot be formed. It also seems that nucleosides serve as poor carbon sources for cya and crp mutants; this could not solely be explained by low levels of nucleoside metabolizing enzymes nor by a deficiency in nucleoside uptake. Addition of casamino acids stimulated the growth of cya and crp mutants, with nucleosides as carbon sources. When grown on glucose and casamino acids growth could be stimulated by adenine and hypoxanthine nucleosides; these results suggest an impaired nitrogen metabolism in cya and crp mutants."}
{"id": "PMID:186710", "title": "Mutliple hepatitis viruses in multiple attacks of acute viral hepatitis.", "content": "We evaluated the causes of 30 episodes of acute viral hepatitis in 13 patients who had multiple attacks. Two (seven per cent) of 30 bouts were caused by hepatitis A virus, and 12 (40%) by hepatitis B virus. No patient, however, had more than one attack with the serologic characteristics of Type A or Type B disease. Thus, there were 16 bouts (53 per cent) not attributable to either of the two recognized hepatitis viruses. None of these \"non-A, non-B\" episodes, evaluated for infectious mononucleosis and cytomegalovirus infection, could be ascribed to either. From this evidence, therefore, it appears that the clinical syndrome of viral hepatitis is produced not only by the two viruses (hepatitis A virus and hepatitis B virus) recognized since the 1940's but also, in all probability, by two non-A, non-B agents.", "contents": "Mutliple hepatitis viruses in multiple attacks of acute viral hepatitis. We evaluated the causes of 30 episodes of acute viral hepatitis in 13 patients who had multiple attacks. Two (seven per cent) of 30 bouts were caused by hepatitis A virus, and 12 (40%) by hepatitis B virus. No patient, however, had more than one attack with the serologic characteristics of Type A or Type B disease. Thus, there were 16 bouts (53 per cent) not attributable to either of the two recognized hepatitis viruses. None of these \"non-A, non-B\" episodes, evaluated for infectious mononucleosis and cytomegalovirus infection, could be ascribed to either. From this evidence, therefore, it appears that the clinical syndrome of viral hepatitis is produced not only by the two viruses (hepatitis A virus and hepatitis B virus) recognized since the 1940's but also, in all probability, by two non-A, non-B agents."}
{"id": "PMID:186711", "title": "Effects of adenine and cytokinins on growth and protein kinase activity of Verticillium albo-atrum.", "content": "Growth of Verticillium albo-atrum in liquid Czapek-Dox broth was stimulated about four-fold by added 10 mM adenine, N6-benzyladenine, or kinetin. Less stimulation was evident at lower concentrations. With none of these included in the basal growth medium, detectable protein kinase activity in cell-free extracts was low and responded minimally to cAMP (adenosine 3',5'-cyclic monophosphate) in the reaction mixture. With each of these compounds as an additive to the growth medium, protein kinase activity was not only greater but also responded markedly (several fold) to cAMP. These results demonstrate a strong correlation between exogenously supplied adenine and related compounds, increased growth, increased protein kinase activity, and kinase response to cAMP in this organism.", "contents": "Effects of adenine and cytokinins on growth and protein kinase activity of Verticillium albo-atrum. Growth of Verticillium albo-atrum in liquid Czapek-Dox broth was stimulated about four-fold by added 10 mM adenine, N6-benzyladenine, or kinetin. Less stimulation was evident at lower concentrations. With none of these included in the basal growth medium, detectable protein kinase activity in cell-free extracts was low and responded minimally to cAMP (adenosine 3',5'-cyclic monophosphate) in the reaction mixture. With each of these compounds as an additive to the growth medium, protein kinase activity was not only greater but also responded markedly (several fold) to cAMP. These results demonstrate a strong correlation between exogenously supplied adenine and related compounds, increased growth, increased protein kinase activity, and kinase response to cAMP in this organism."}
{"id": "PMID:186712", "title": "[Behavior of certain parameters of lipid and energy metabolism. 3. Relationships between cyclic 3',5'-adenosine monophosphate and acetyl coenzyme A in liver of growing rats deduced from model experiments with diets differeing in fat content].", "content": "Schemes of the lipid and the pyruvate metabolism serve to show that a great part of the enzymes which intervence in the metabolic pathways and are associated with the formation and the consumption of acetyl coenzyme A may be regulated by cyclic 3',5'-adenosine monophosphate (cAMP) in the sense of activation or inhibition. The cAMP increase in the liver, which has been demonstrated in the present study for a diet containing 25% of fat, opens the metabolic pathway to the formation of acetyl coenzyme A by means of fatty acid degradation and simultaneous inhibition of lipogenesis. The deficiency of insulin (which has been evidenced in previous paper) characterizes, together with the facts mentioned, a state like diabetes or the fasting state. Acetyl coenzyme A is mainly used for energy supply. The close negative correlation between cAMP and acetyl coenzyme A (which is shown in the present paper) permits to conclude that the extent and trend of the increase and decrease in the liver is subjected to intensive hormonal control in which cAMP in involved.", "contents": "[Behavior of certain parameters of lipid and energy metabolism. 3. Relationships between cyclic 3',5'-adenosine monophosphate and acetyl coenzyme A in liver of growing rats deduced from model experiments with diets differeing in fat content]. Schemes of the lipid and the pyruvate metabolism serve to show that a great part of the enzymes which intervence in the metabolic pathways and are associated with the formation and the consumption of acetyl coenzyme A may be regulated by cyclic 3',5'-adenosine monophosphate (cAMP) in the sense of activation or inhibition. The cAMP increase in the liver, which has been demonstrated in the present study for a diet containing 25% of fat, opens the metabolic pathway to the formation of acetyl coenzyme A by means of fatty acid degradation and simultaneous inhibition of lipogenesis. The deficiency of insulin (which has been evidenced in previous paper) characterizes, together with the facts mentioned, a state like diabetes or the fasting state. Acetyl coenzyme A is mainly used for energy supply. The close negative correlation between cAMP and acetyl coenzyme A (which is shown in the present paper) permits to conclude that the extent and trend of the increase and decrease in the liver is subjected to intensive hormonal control in which cAMP in involved."}
{"id": "PMID:186720", "title": "Quantal parameters of transmission at the frog neuromuscular junction.", "content": "Estimates of quantal release parameters at frog neuromuscular junctions showed that alterations in [Ca2+]o affected m (number of quanta), p (probability of quantal release) and n (stores of quanta available for release). The effect of [Ca2+]o depended upon the initial value for p. When p was low, raising [Ca2+]o increased m and p, but not n. However, when p was large, raising [Ca2+]o had no further effect on p but increased m and n. During prolonged repetitive nerve stimulation to cause a decrease in m, n was decreased and p was increased. This finding was attributed to a failure of transmitter mobilization to maintain the stores of transmitter available for release.", "contents": "Quantal parameters of transmission at the frog neuromuscular junction. Estimates of quantal release parameters at frog neuromuscular junctions showed that alterations in [Ca2+]o affected m (number of quanta), p (probability of quantal release) and n (stores of quanta available for release). The effect of [Ca2+]o depended upon the initial value for p. When p was low, raising [Ca2+]o increased m and p, but not n. However, when p was large, raising [Ca2+]o had no further effect on p but increased m and n. During prolonged repetitive nerve stimulation to cause a decrease in m, n was decreased and p was increased. This finding was attributed to a failure of transmitter mobilization to maintain the stores of transmitter available for release."}
{"id": "PMID:186721", "title": "Relationship between the level of cAMP and the contractile force under stimulation of alpha- and beta-adrenoceptors by phenylephrine in the isolated rabbit papillary muscle.", "content": "The time course of changes of the level of 3',5'-cyclic AMP (cAMP) and of the tension developed under stimulation of alpha- and beta-adrenoceptors by phenylephrine was investigated in the isolated rabbit papillary muscle. Furthermore the dose-response relationships for increases of cAMP and of developed tension elicited by phenylephrine were determined. 1. A submaximally effective concentration of phenylephrine (10(-5) M) increased significantly the level of cAMP of the papillary muscle at 15 and 30 s by 45 and 36% respectively; the level of cAMP returned to the control value at 60 s after the administration. The developed tension increased significantly not before 45 s and reached its maximal level at 180 s. 2. When alpha-adrenoceptors were blocked by phentolamine (10(-6) M), the positive inotropic effect of phenylephrine was decreased significantly but the increase of cAMP induced by phenylephrine was not reduced. In the presence of phentolamine the increase of cAMP induced by phenylephrine lasted longer than in the control experiments. 3. The effects of phenylephrine (10(-5) M) both on the level of cAMP and the developed tension mediated via stimulation of beta-adrenoceptors in the presence of phentolamine were enhanced by the phosphodiesterase inhibitor papaverine throughout the course of responses. 4. Phenylephrine produced an increase in developed tension as well as in cAMP. The corresponding dose-response curves run parallel to each other but differed by about 1.5 log units whereby the developed tension was evoked by lower concentrations. Phentolamine (10(-6) M) shifted the curve for the positive inotropic action by about 1.5 log units but did not affect that for increase in cAMP. Therefore, in the presence of the alpha-adrenolytic drug phentolamine the difference between both curves became smaller so that both curves were superimposed. Papaverine (10(-5) M) shifted the whole curve for cAMP upwards and enhanced the maximal contractile response to phenylephrine mediated by stimulation of beta-adrenoceptors. 5. The present results indicate that the positive inotropic action of phenylephrine in lower concentrations (less than 10(-5) M) induced by stimulation of alpha-adrenoceptors is independent of the level of cAMP. The positive inotropic action of the higher concentrations of phenylephrine induced via stimulation of beta-adrenoceptors was preceded by an accumulation of cAMP; the inhibition of the cAMP phosphodiesterase activity by papaverine enhanced the actions of phenylephrine both on the level of cAMP and on the contractile force.", "contents": "Relationship between the level of cAMP and the contractile force under stimulation of alpha- and beta-adrenoceptors by phenylephrine in the isolated rabbit papillary muscle. The time course of changes of the level of 3',5'-cyclic AMP (cAMP) and of the tension developed under stimulation of alpha- and beta-adrenoceptors by phenylephrine was investigated in the isolated rabbit papillary muscle. Furthermore the dose-response relationships for increases of cAMP and of developed tension elicited by phenylephrine were determined. 1. A submaximally effective concentration of phenylephrine (10(-5) M) increased significantly the level of cAMP of the papillary muscle at 15 and 30 s by 45 and 36% respectively; the level of cAMP returned to the control value at 60 s after the administration. The developed tension increased significantly not before 45 s and reached its maximal level at 180 s. 2. When alpha-adrenoceptors were blocked by phentolamine (10(-6) M), the positive inotropic effect of phenylephrine was decreased significantly but the increase of cAMP induced by phenylephrine was not reduced. In the presence of phentolamine the increase of cAMP induced by phenylephrine lasted longer than in the control experiments. 3. The effects of phenylephrine (10(-5) M) both on the level of cAMP and the developed tension mediated via stimulation of beta-adrenoceptors in the presence of phentolamine were enhanced by the phosphodiesterase inhibitor papaverine throughout the course of responses. 4. Phenylephrine produced an increase in developed tension as well as in cAMP. The corresponding dose-response curves run parallel to each other but differed by about 1.5 log units whereby the developed tension was evoked by lower concentrations. Phentolamine (10(-6) M) shifted the curve for the positive inotropic action by about 1.5 log units but did not affect that for increase in cAMP. Therefore, in the presence of the alpha-adrenolytic drug phentolamine the difference between both curves became smaller so that both curves were superimposed. Papaverine (10(-5) M) shifted the whole curve for cAMP upwards and enhanced the maximal contractile response to phenylephrine mediated by stimulation of beta-adrenoceptors. 5. The present results indicate that the positive inotropic action of phenylephrine in lower concentrations (less than 10(-5) M) induced by stimulation of alpha-adrenoceptors is independent of the level of cAMP. The positive inotropic action of the higher concentrations of phenylephrine induced via stimulation of beta-adrenoceptors was preceded by an accumulation of cAMP; the inhibition of the cAMP phosphodiesterase activity by papaverine enhanced the actions of phenylephrine both on the level of cAMP and on the contractile force."}
{"id": "PMID:186722", "title": "Binding of botulinum neurotoxin to the synaptosome fraction of rat brain.", "content": "The radioactive 125I-labelled neurotoxin of C. botulinum type A, when incubated with rat brain homogenate, is bound selectively to the synaptosome fraction. Intact toxin was liberated from the synaptosome fraction by treatment with Triton X-100, SDS, trypsin or neuraminidase.", "contents": "Binding of botulinum neurotoxin to the synaptosome fraction of rat brain. The radioactive 125I-labelled neurotoxin of C. botulinum type A, when incubated with rat brain homogenate, is bound selectively to the synaptosome fraction. Intact toxin was liberated from the synaptosome fraction by treatment with Triton X-100, SDS, trypsin or neuraminidase."}
{"id": "PMID:186724", "title": "[Adenoid cystic carcinoma extended to Gasserian ganglion-report of two cases (author's transl)].", "content": "Adenoid cystic carcinoma is an uncommon tumor, especially in cases of its extension into the cranial cavity. Two cases of this tumor involving Gasserian ganglion were reported. The first case was a 47 year old female who developed paresis of the right side fifth cranial nerve. The plain skull X-ray of the axial view demonstrated enlargement of the right sided foramen ovale. The tumor was removed exploring the middle fossa extradurally, however its extention through the foramen ovale remained behind. A small induration was found at the base of the oral cavity postoperatively, and the biopsy revealed characteristic findings of adenoid cystic carcinoma histologically. Radiation therapy was followed by considerable clinical improvement.", "contents": "[Adenoid cystic carcinoma extended to Gasserian ganglion-report of two cases (author's transl)]. Adenoid cystic carcinoma is an uncommon tumor, especially in cases of its extension into the cranial cavity. Two cases of this tumor involving Gasserian ganglion were reported. The first case was a 47 year old female who developed paresis of the right side fifth cranial nerve. The plain skull X-ray of the axial view demonstrated enlargement of the right sided foramen ovale. The tumor was removed exploring the middle fossa extradurally, however its extention through the foramen ovale remained behind. A small induration was found at the base of the oral cavity postoperatively, and the biopsy revealed characteristic findings of adenoid cystic carcinoma histologically. Radiation therapy was followed by considerable clinical improvement."}
{"id": "PMID:186726", "title": "Autopsy correlations of computerized tomography: experience with 6,000 CT scans.", "content": "Seventy-nine autopsy correlations of CT scans showed (1) excellent correlations in normal brains, but the size of the lateral ventricles consistently larger during life than after death; (2) a distinctive pattern differentiating obstructive from nonobstructive hydrocephalus; (3) infarctions appearing as areas of decreased densities of parenchyma in vascular distributions; (4) distinctive high density appearances of hemorrhages that differentiated them from infarctions and, in general, all other pathologic processes; (5) supratentorial, intraventricular, and posterior fossa tumors appearing as masses that displaced, distorted, collapsed, and enlarged normal spaces and structures such as ventricles and pineal gland; (6) 11 false-negative CT scans in some cases of brain stem infarction, brain stem hemorrhage, and small metastasis; and (7) an overall accuracy of 86.2 percent of CT scanning in correctly identifying pathology of the brain.", "contents": "Autopsy correlations of computerized tomography: experience with 6,000 CT scans. Seventy-nine autopsy correlations of CT scans showed (1) excellent correlations in normal brains, but the size of the lateral ventricles consistently larger during life than after death; (2) a distinctive pattern differentiating obstructive from nonobstructive hydrocephalus; (3) infarctions appearing as areas of decreased densities of parenchyma in vascular distributions; (4) distinctive high density appearances of hemorrhages that differentiated them from infarctions and, in general, all other pathologic processes; (5) supratentorial, intraventricular, and posterior fossa tumors appearing as masses that displaced, distorted, collapsed, and enlarged normal spaces and structures such as ventricles and pineal gland; (6) 11 false-negative CT scans in some cases of brain stem infarction, brain stem hemorrhage, and small metastasis; and (7) an overall accuracy of 86.2 percent of CT scanning in correctly identifying pathology of the brain."}
{"id": "PMID:186727", "title": "[Motor nerve conduction velocity in arterial hypertension].", "content": "Motor nerve conduction velocity was studied in a group of 44 hypertensive patients; velocity was measured at the level of the median and external popliteal sciatic nerves. From the series were excluded those hypertensive subjects with renal insufficiency, diabetes mellitus and peripheral arterial disease. No significant differences were observed in MNCV values compared to controls. Within the hypertense group, no appreciable variations were observed depending on the duration and degree of hypertension, and signs of visceral damage (assessed at myocardial and retinic levels). The results do not confirm previous published data suggesting the existence of MNCV reduction during arterial hypertension, the reduction being considered an subclinical expression of peripheral neuropathy and an index of the gravity of visceral damage during hypertensive disease.", "contents": "[Motor nerve conduction velocity in arterial hypertension]. Motor nerve conduction velocity was studied in a group of 44 hypertensive patients; velocity was measured at the level of the median and external popliteal sciatic nerves. From the series were excluded those hypertensive subjects with renal insufficiency, diabetes mellitus and peripheral arterial disease. No significant differences were observed in MNCV values compared to controls. Within the hypertense group, no appreciable variations were observed depending on the duration and degree of hypertension, and signs of visceral damage (assessed at myocardial and retinic levels). The results do not confirm previous published data suggesting the existence of MNCV reduction during arterial hypertension, the reduction being considered an subclinical expression of peripheral neuropathy and an index of the gravity of visceral damage during hypertensive disease."}
{"id": "PMID:186723", "title": "[Polyneuropathy syndrome in a case of spinal meningeal carcinomatosis].", "content": "The authors report a case of polyneuropathy of lower extremities developing in carcinomatosis of spinal meninges in a patient after gastrectomy for mucus-producing carcinoma.", "contents": "[Polyneuropathy syndrome in a case of spinal meningeal carcinomatosis]. The authors report a case of polyneuropathy of lower extremities developing in carcinomatosis of spinal meninges in a patient after gastrectomy for mucus-producing carcinoma."}
{"id": "PMID:186733", "title": "Isolated ACTH deficiency and pregnancy.", "content": "Isolated deficiences of anterior pituitary hormones are rare. A patient is presented whose hypoglycemia during pregnancy resulted from ACTH deficiency. Glucocorticoid treatment enabled her to complete pregnancy successfully. In addition, she did not menstruate during an interval in which she did not receive glucocorticoid therapy. The dynamics of fetal and maternal glucose metabolism are discussed as well as menstruation and fertility in adrenal insufficiency.", "contents": "Isolated ACTH deficiency and pregnancy. Isolated deficiences of anterior pituitary hormones are rare. A patient is presented whose hypoglycemia during pregnancy resulted from ACTH deficiency. Glucocorticoid treatment enabled her to complete pregnancy successfully. In addition, she did not menstruate during an interval in which she did not receive glucocorticoid therapy. The dynamics of fetal and maternal glucose metabolism are discussed as well as menstruation and fertility in adrenal insufficiency."}
{"id": "PMID:186740", "title": "A prevalence study of oral mucosal lesions in an adult Swedish population.", "content": "The prevalence of oral mucosal lesions in Sweden is virtually unknown. Available prevalence figures concern but a few types of lesions and relate to highly selected, special populations. Investigations on general populations are sparse also in other countries. The aim of the present study was to survey the occurrence of oral mucosal lesions in a relatively large general population in Sweden. The study was performed in collaboration with a health screening organization in the middle of Sweden. The populations of two municipalities in the County of Uppsala were investigated. A mobile health screening group visited several places in the selected area and during the time of the present investigation a total of 30,118 persons, aged 15 years or above, were summoned. Of these, 62% or 18.659 individuals attended and were examined. The non-participants became the subject of a special investigation for which every fifth individual, or 2.292 persons, was randomly sampled. After a second summons, 933 persons presented for examination. Through personal contact, an additional 741 individuals were examined in private homes, places of work, hospitals, old age homes and other institutions. The final non-participation, representing 10.3% of the total population, was considered to have but a marginal influence on the results of the study. The diagnostic procedure was based on clinical criteria set forth especially for the investigation. The validity of the final diagnoses was evaluated by, for instance, inter-examiner tests and comparisons between clinical diagnoses and histologic descriptions and was found to be acceptable. Tests of the reliability were, among else, undertaken through re-examinations and indicated, that underregistration apparently occurred for a few of the lesions investigated. The prevalences of about 60 oral mucosal lesions were recorded and compared with previous findings. Notably high prevalences were found for focal epithelial hyperplasia (0.11%), leukoedema (49.07%), geographic tongue (8.45%) and lichen planus (1.85%). For some lesions prevalence figures are difficult to compare with findings from previous studies. This includes lesions which are directly or indirectly related to local etiologic factors such as denture status and tobacco habits. As regards these factors basic information has been collected and will be used for further analyses. The collected total material has also been designed to form the basis for longitudinal studies of, for example, precancerous lesions.", "contents": "A prevalence study of oral mucosal lesions in an adult Swedish population. The prevalence of oral mucosal lesions in Sweden is virtually unknown. Available prevalence figures concern but a few types of lesions and relate to highly selected, special populations. Investigations on general populations are sparse also in other countries. The aim of the present study was to survey the occurrence of oral mucosal lesions in a relatively large general population in Sweden. The study was performed in collaboration with a health screening organization in the middle of Sweden. The populations of two municipalities in the County of Uppsala were investigated. A mobile health screening group visited several places in the selected area and during the time of the present investigation a total of 30,118 persons, aged 15 years or above, were summoned. Of these, 62% or 18.659 individuals attended and were examined. The non-participants became the subject of a special investigation for which every fifth individual, or 2.292 persons, was randomly sampled. After a second summons, 933 persons presented for examination. Through personal contact, an additional 741 individuals were examined in private homes, places of work, hospitals, old age homes and other institutions. The final non-participation, representing 10.3% of the total population, was considered to have but a marginal influence on the results of the study. The diagnostic procedure was based on clinical criteria set forth especially for the investigation. The validity of the final diagnoses was evaluated by, for instance, inter-examiner tests and comparisons between clinical diagnoses and histologic descriptions and was found to be acceptable. Tests of the reliability were, among else, undertaken through re-examinations and indicated, that underregistration apparently occurred for a few of the lesions investigated. The prevalences of about 60 oral mucosal lesions were recorded and compared with previous findings. Notably high prevalences were found for focal epithelial hyperplasia (0.11%), leukoedema (49.07%), geographic tongue (8.45%) and lichen planus (1.85%). For some lesions prevalence figures are difficult to compare with findings from previous studies. This includes lesions which are directly or indirectly related to local etiologic factors such as denture status and tobacco habits. As regards these factors basic information has been collected and will be used for further analyses. The collected total material has also been designed to form the basis for longitudinal studies of, for example, precancerous lesions."}
{"id": "PMID:186742", "title": "Studies on kinetics of DNA synthesis in CV-1 cell cultures infected with different multiplicities (MOI) of Herpes simplex virus type 2 (HSV-2).", "content": "Infection of CV-1 cell cultures with HSV-2 at MOI 5 respectively 1PFU/cell resulted in markedly different patterns of DNA-synthesis. Isolation and separation of cellular and viral DNA on CsCl equilibrium density gradients during the \"late\" phase after infection with 5PFU/cell revealed a rapid increase in synthesis of virus-specific DNA (which banded at density q25 = 1.729 g/ccm) while synthesis of host cell DNA (banding at 1.705 g/ccm) was constantly inhibited. 15 hours after infection and incubation with labelled medium, around infection and incubation with labelled medium, around 75% of total isolated DNA was virus-specific. On lowering the MOI to 1 PFU/cell, however, synthesis of host cell DNA continued and was even partially stimulated during the late phase whereas synthesis of virus-specific DNA advanced only slowly. 16 hours after infection, approximately 25% of the total assayed after infection, approximately 25% of the total assayed DNA was virus-specific and the amount of host cell DNA approached values of uninfected control cells. 24 hours after infection and incubation, virus specific DNA rose to approximately 45% of overall DNA assayed, and synthesis of host cell DNA was completely inhibited. However, infectivity rose constantly and reached 106.8 TCD 50/ml at 22 hours p.i. These findings were independent of passage number of CV-cell culture, and there were no alterations in karyotype and morphological behaviour of the cells.", "contents": "Studies on kinetics of DNA synthesis in CV-1 cell cultures infected with different multiplicities (MOI) of Herpes simplex virus type 2 (HSV-2). Infection of CV-1 cell cultures with HSV-2 at MOI 5 respectively 1PFU/cell resulted in markedly different patterns of DNA-synthesis. Isolation and separation of cellular and viral DNA on CsCl equilibrium density gradients during the \"late\" phase after infection with 5PFU/cell revealed a rapid increase in synthesis of virus-specific DNA (which banded at density q25 = 1.729 g/ccm) while synthesis of host cell DNA (banding at 1.705 g/ccm) was constantly inhibited. 15 hours after infection and incubation with labelled medium, around infection and incubation with labelled medium, around 75% of total isolated DNA was virus-specific. On lowering the MOI to 1 PFU/cell, however, synthesis of host cell DNA continued and was even partially stimulated during the late phase whereas synthesis of virus-specific DNA advanced only slowly. 16 hours after infection, approximately 25% of the total assayed after infection, approximately 25% of the total assayed DNA was virus-specific and the amount of host cell DNA approached values of uninfected control cells. 24 hours after infection and incubation, virus specific DNA rose to approximately 45% of overall DNA assayed, and synthesis of host cell DNA was completely inhibited. However, infectivity rose constantly and reached 106.8 TCD 50/ml at 22 hours p.i. These findings were independent of passage number of CV-cell culture, and there were no alterations in karyotype and morphological behaviour of the cells."}
{"id": "PMID:186745", "title": "[Blood lipoprotein transfers in the normal arterial wall. Study auto-historadiography in optic microscopy].", "content": "In order to study the mecanisms of serum lipoproteins transfers and binding sites in arterial wall, auto-historadiographies in optical microscopy were realised with rats aortas. Animals received infusion of in vivo labelled on the cholesterol and purified serum lipoproteins. The results confirmed the serum lipoproteins transfers in arterial wall and slow that the inflow is all the more quicker and higher as the molecule is smaller. The very particular aspect of these transfers rises several hypothesis and leeds to suggest the possibility of preferential way of passage inside the arterial wall.", "contents": "[Blood lipoprotein transfers in the normal arterial wall. Study auto-historadiography in optic microscopy]. In order to study the mecanisms of serum lipoproteins transfers and binding sites in arterial wall, auto-historadiographies in optical microscopy were realised with rats aortas. Animals received infusion of in vivo labelled on the cholesterol and purified serum lipoproteins. The results confirmed the serum lipoproteins transfers in arterial wall and slow that the inflow is all the more quicker and higher as the molecule is smaller. The very particular aspect of these transfers rises several hypothesis and leeds to suggest the possibility of preferential way of passage inside the arterial wall."}
{"id": "PMID:186746", "title": "Historadioautographic and biochemical studies on the transport of atherogenic lipoproteins into the rabbit aortic wall.", "content": "Historadioautographic and biochemical studies were undertaken on the transport of 14C-labelled serum very low density and low density lipoproteins (VLDL and LDL respectively) into the aortic wall. Aortas from normal and atherosclerotic rabbits were perfused in vitro with a medium containing VLDL and LDL for 6 hours. Historadioautography revealed the label in all the layers of the perfused aorta. The gradient in the distribution of this label from the inner layers of the aortic wall dawn to the outer part of the media demonstrated that lipoprotein infiltration of the vessel wall is due to uptake of lipoproteins from the aortic lumen. The non-uniform pattern of the distribution of lipoproteins taken up by the atherosclerotic aorta was considered as a result of atherogenesis induced changes in the aortic connective tissue. Both morphological and biochemical studies revealed the increased permeability of the atherosclerotic aortic wall to VLDL and LDL, which appeared to penetrate the walls of blood vessels in the form of intact particles.", "contents": "Historadioautographic and biochemical studies on the transport of atherogenic lipoproteins into the rabbit aortic wall. Historadioautographic and biochemical studies were undertaken on the transport of 14C-labelled serum very low density and low density lipoproteins (VLDL and LDL respectively) into the aortic wall. Aortas from normal and atherosclerotic rabbits were perfused in vitro with a medium containing VLDL and LDL for 6 hours. Historadioautography revealed the label in all the layers of the perfused aorta. The gradient in the distribution of this label from the inner layers of the aortic wall dawn to the outer part of the media demonstrated that lipoprotein infiltration of the vessel wall is due to uptake of lipoproteins from the aortic lumen. The non-uniform pattern of the distribution of lipoproteins taken up by the atherosclerotic aorta was considered as a result of atherogenesis induced changes in the aortic connective tissue. Both morphological and biochemical studies revealed the increased permeability of the atherosclerotic aortic wall to VLDL and LDL, which appeared to penetrate the walls of blood vessels in the form of intact particles."}
{"id": "PMID:186747", "title": "Atopic dermatitis: etiology and pathogenesis.", "content": "Atopic dermatitis is a recognizable phenotype that most likely results from several mechanisms. An increasing number of children with atopic dermatitis are recognized as having immune defects, although the exact incidence of such immunodeficiency states among patients with atopic dermatitis is unknown. Children with atopic dermatitis who suffer recurrent or persistent infections should undergo immunologic evaluation. Ideally, this should include evaluation of cell-mediated immunity as well as neutrophil and monocyte chemotaxis. Further investigation into the beta-blockade theory may enhance our understanding of atopic dermatitis. Careful attention to factors exacerbating atopic dermatitis is essential in understanding this problem. Abnormal sweating, dry skin, sensitivity to contactants, and emotional stress should always be considered in evaluation of children with atopic dermatitis.", "contents": "Atopic dermatitis: etiology and pathogenesis. Atopic dermatitis is a recognizable phenotype that most likely results from several mechanisms. An increasing number of children with atopic dermatitis are recognized as having immune defects, although the exact incidence of such immunodeficiency states among patients with atopic dermatitis is unknown. Children with atopic dermatitis who suffer recurrent or persistent infections should undergo immunologic evaluation. Ideally, this should include evaluation of cell-mediated immunity as well as neutrophil and monocyte chemotaxis. Further investigation into the beta-blockade theory may enhance our understanding of atopic dermatitis. Careful attention to factors exacerbating atopic dermatitis is essential in understanding this problem. Abnormal sweating, dry skin, sensitivity to contactants, and emotional stress should always be considered in evaluation of children with atopic dermatitis."}
{"id": "PMID:186752", "title": "Dietary lipid and postnatal development. II. Palmityl coenzyme A oxidation in heart and liver.", "content": "There is only indirect evidence to suggest that the sudden postpartum appearance of dietary lipid regulates the perinatal development of the enzyme pathways required for fatty acid oxidation. To test this idea directly, rabbit pups were maintained on diets containing lipid to equal either 14.2% (LF) or 77.6% (HF) of the total caloric intake. Palmityl coenzyme A oxidation rates in the presence of excess ADP and carnitine were measured polarographically in heart and liver homogenates. No significant difference in oxidation rates between HF and LF groups was observed even at 10 days of age. Palmityl coenzyme A oxidation in both groups was carnitine dependent and was in general the same as that of mother-fed animals. Similarly, an evaluation of cytochrome oxidase activity and glutamate + malate-supported respiration in heart and liver homogenates revealed no difference attributable to diet. To consider the possibility that fatty acid oxidation might be specifically increased or decreased over other mitochondrial respiratory activity as a function of diet, palmityl coenzyme A oxidation rates were normalized with respect to glutamate + malate oxidation rates. A similar comparison was made relative to cytochrome oxidase activity. Still no differences were observed between HF and LF groups. By studying the maximum rate of oxygen utilization in the presence of excess carnitine and palmityl-coenzyme A we would have detected any change in a rate-limiting step for fatty acid oxidation beyond acyl activation. We must conclude, therefore, that large differences in the proportion of postnatal dietary lipid do no influence the cellular capacity to oxidize palmityl coenzyme A.", "contents": "Dietary lipid and postnatal development. II. Palmityl coenzyme A oxidation in heart and liver. There is only indirect evidence to suggest that the sudden postpartum appearance of dietary lipid regulates the perinatal development of the enzyme pathways required for fatty acid oxidation. To test this idea directly, rabbit pups were maintained on diets containing lipid to equal either 14.2% (LF) or 77.6% (HF) of the total caloric intake. Palmityl coenzyme A oxidation rates in the presence of excess ADP and carnitine were measured polarographically in heart and liver homogenates. No significant difference in oxidation rates between HF and LF groups was observed even at 10 days of age. Palmityl coenzyme A oxidation in both groups was carnitine dependent and was in general the same as that of mother-fed animals. Similarly, an evaluation of cytochrome oxidase activity and glutamate + malate-supported respiration in heart and liver homogenates revealed no difference attributable to diet. To consider the possibility that fatty acid oxidation might be specifically increased or decreased over other mitochondrial respiratory activity as a function of diet, palmityl coenzyme A oxidation rates were normalized with respect to glutamate + malate oxidation rates. A similar comparison was made relative to cytochrome oxidase activity. Still no differences were observed between HF and LF groups. By studying the maximum rate of oxygen utilization in the presence of excess carnitine and palmityl-coenzyme A we would have detected any change in a rate-limiting step for fatty acid oxidation beyond acyl activation. We must conclude, therefore, that large differences in the proportion of postnatal dietary lipid do no influence the cellular capacity to oxidize palmityl coenzyme A."}
{"id": "PMID:186753", "title": "Encephalitis in infectious mononucleosis: diagnostic considerations.", "content": "Four atypical cases of presumed infectious mononucleosis (IM) encephalitis are presented. To establish an etiologic diagnosis, Paul-Bunnell-Davidsohn heterophil titers (PBD), antibody titers to the antigens of the Epstein-Barr virus (EBV), and oropharyngeal excretion of EBV were determined. Criteria for a primary EBV infection are (1) an antiviral capsid antigen titer of 1:160 or greater, (2) the presence of antibody to the diffuse component of the early antigen, (3) absence of antibody to the nuclear antigen, and (4) excretion of the virus from the oropharynx. Three of the four cases met these criteria; of the three, one did not have a positive heterophil titer. The fourth case turned out not to be IM; there was a positive PBD heterophil, but there was no evidence of primary EBV infection. Although the PBD heterophil is usually a reliable test to diagnosis IM, it is not always present in children, and it is sometimes nonspecifically elevated. Some EBV titers can be nonspecifically elevated as well; however, the above criteria are diagnostic of primary EBV infection.", "contents": "Encephalitis in infectious mononucleosis: diagnostic considerations. Four atypical cases of presumed infectious mononucleosis (IM) encephalitis are presented. To establish an etiologic diagnosis, Paul-Bunnell-Davidsohn heterophil titers (PBD), antibody titers to the antigens of the Epstein-Barr virus (EBV), and oropharyngeal excretion of EBV were determined. Criteria for a primary EBV infection are (1) an antiviral capsid antigen titer of 1:160 or greater, (2) the presence of antibody to the diffuse component of the early antigen, (3) absence of antibody to the nuclear antigen, and (4) excretion of the virus from the oropharynx. Three of the four cases met these criteria; of the three, one did not have a positive heterophil titer. The fourth case turned out not to be IM; there was a positive PBD heterophil, but there was no evidence of primary EBV infection. Although the PBD heterophil is usually a reliable test to diagnosis IM, it is not always present in children, and it is sometimes nonspecifically elevated. Some EBV titers can be nonspecifically elevated as well; however, the above criteria are diagnostic of primary EBV infection."}
{"id": "PMID:186754", "title": "The dynamics of insulin release from mouse pancreatic islet cells in suspension.", "content": "The overall dynamics of glucose-induced insulin release was strikingly similar in dispersed cells and intact islets perifused in parallel. Both preparations exhibited a latency of 1-2 min, after which period there was a brisk rise of insulin release followed by a sustained second phase. During the second phase, insulin release from dispersed cells attained a stable plateau rate, whereas the release from intact islets continued to rise. Epinephrine (1 muM) inhibited the release in both preparations, but the return to basal rate was faster in the dispersed cells than in the intact islets. The dispersed cells oxidized glucose at a constant rate for at least 60 min; the glucose oxidation was markedly sensitive to changes of the glucose concentration in the range of 3-20 mM.", "contents": "The dynamics of insulin release from mouse pancreatic islet cells in suspension. The overall dynamics of glucose-induced insulin release was strikingly similar in dispersed cells and intact islets perifused in parallel. Both preparations exhibited a latency of 1-2 min, after which period there was a brisk rise of insulin release followed by a sustained second phase. During the second phase, insulin release from dispersed cells attained a stable plateau rate, whereas the release from intact islets continued to rise. Epinephrine (1 muM) inhibited the release in both preparations, but the return to basal rate was faster in the dispersed cells than in the intact islets. The dispersed cells oxidized glucose at a constant rate for at least 60 min; the glucose oxidation was markedly sensitive to changes of the glucose concentration in the range of 3-20 mM."}
{"id": "PMID:186755", "title": "Loss of ATP in micromolar amounts after perchloric acid treatment.", "content": "Treatment of fluid samples containing known amounts of ATP with 6.0 N perchloric acid (PCA) results in a total loss of 65-71% when the initial concentrations of ATP ranged between 0.5 to 50 muM. Half of this loss was attributed to desensitization of firefly extract (luciferin-luciferase reaction) while the remaining loss was presumably due to adsorption of ATP to perchlorate precipitate upon neutralization. Similar treatment of solutions with higher initial concentrations (100-1000 muM) resulted in apparent total losses averaging 22%. These losses were due solely to desensitization of firefly extract by neutralized PCA. Both the adsorption and desensitization phenomena must be taken into account when the ATP content is measured from tissue extracts and fluid samples subjected to this procedure.", "contents": "Loss of ATP in micromolar amounts after perchloric acid treatment. Treatment of fluid samples containing known amounts of ATP with 6.0 N perchloric acid (PCA) results in a total loss of 65-71% when the initial concentrations of ATP ranged between 0.5 to 50 muM. Half of this loss was attributed to desensitization of firefly extract (luciferin-luciferase reaction) while the remaining loss was presumably due to adsorption of ATP to perchlorate precipitate upon neutralization. Similar treatment of solutions with higher initial concentrations (100-1000 muM) resulted in apparent total losses averaging 22%. These losses were due solely to desensitization of firefly extract by neutralized PCA. Both the adsorption and desensitization phenomena must be taken into account when the ATP content is measured from tissue extracts and fluid samples subjected to this procedure."}
{"id": "PMID:186756", "title": "Negative inotropic effect of cyclic GMP in cardiac fiber fragments.", "content": "The force of spontaneously beating cardiac cellular fragments obtained from mice heart by homogenization was recorded in presence of cyclic guanosine -3'.5'-monophosphate (cGMP) and cyclic 8-bromguanosine -3'.5'-monophosphate in concentrations of 3 X 10(-6) M - 33 X 10(-6) M. The nucleotide decreased the force and reduced the rate of spontaneity. Eventually the preparation became quiescent. It is thought that this nucleotide either reduces the capacity to sequester calcium or affects its release from the sarcotubular system.", "contents": "Negative inotropic effect of cyclic GMP in cardiac fiber fragments. The force of spontaneously beating cardiac cellular fragments obtained from mice heart by homogenization was recorded in presence of cyclic guanosine -3'.5'-monophosphate (cGMP) and cyclic 8-bromguanosine -3'.5'-monophosphate in concentrations of 3 X 10(-6) M - 33 X 10(-6) M. The nucleotide decreased the force and reduced the rate of spontaneity. Eventually the preparation became quiescent. It is thought that this nucleotide either reduces the capacity to sequester calcium or affects its release from the sarcotubular system."}
{"id": "PMID:186759", "title": "Conformations of A,T-rich DNAs.", "content": "DNAs from the genomes of Clostridium perfringens and Cytophaga johnsonii display orthodox A-DNA and B-DNA structures despite their high (A+L) nucleotide content. Unique structures, such as those found for synthetic DNAs having specific special sequences, do therefore not necessarily occur for DNAs having more random base sequence even if these have unusual base compositions. Clostridium perfringens DNA exhibits unusual structural properties only prior to purification by gel filtration.", "contents": "Conformations of A,T-rich DNAs. DNAs from the genomes of Clostridium perfringens and Cytophaga johnsonii display orthodox A-DNA and B-DNA structures despite their high (A+L) nucleotide content. Unique structures, such as those found for synthetic DNAs having specific special sequences, do therefore not necessarily occur for DNAs having more random base sequence even if these have unusual base compositions. Clostridium perfringens DNA exhibits unusual structural properties only prior to purification by gel filtration."}
{"id": "PMID:186760", "title": "Identification of the minor guanylated tRNA of rabbit reticulocytes.", "content": "Two of the tRNA's found in rabbit reticulocytes are substrates for a post-transcriptional modification leading to the incorporation of guanine into the polynucleotide chain. The major guanylated tRNA was previously identified as tRNA (His). In the present report we show that the minor guanylated tRNA is tRNA (Asn), and that just as in the case of tRNA (His), the guanine is located in an internal position. There are only two tRNA (Asn) in reticulocytes. We further show that one of these, the one that is not labeled with guanine, contains the hypermodified base known as Q. tRNA (Asn) does not contain Q.", "contents": "Identification of the minor guanylated tRNA of rabbit reticulocytes. Two of the tRNA's found in rabbit reticulocytes are substrates for a post-transcriptional modification leading to the incorporation of guanine into the polynucleotide chain. The major guanylated tRNA was previously identified as tRNA (His). In the present report we show that the minor guanylated tRNA is tRNA (Asn), and that just as in the case of tRNA (His), the guanine is located in an internal position. There are only two tRNA (Asn) in reticulocytes. We further show that one of these, the one that is not labeled with guanine, contains the hypermodified base known as Q. tRNA (Asn) does not contain Q."}
{"id": "PMID:186761", "title": "Studies on the interaction of H1 histone with superhelical DNA: characterization of the recognition and binding regions of H1 histones.", "content": "The very lysine rich histone, H1, isolated from a variety of sources interacts preferentially with superhelical DNA compared to relaxed DNA duplexes. The nature of this specific interaction has been investigated by studying the ability of various purified fragments of H1 histone from calf thymus to recognize and bind superhelical DNA. The data suggest that the globular region of the H1 histone molecule (amino acid residues 72-106) is involved in the recognition of superhelical DNA. Thus, the H1 histone carboxy-terminal fragment, 72-212, resembles native H1 histone both quantitatively and qualitatively in its ability to discriminate between and bind to superhelical and relaxed DNA while the H1 histone carboxy-terminal fragment, residues 106-212, has lost this specificity, binding superhelical and relaxed DNA equally well. Furthermore, under conditions in which the globular region of the intact H1 histone has been unfolded, the molecule loses its ability to discriminate between superhelical and relaxed DNA, and binds both forms of DNA equally.", "contents": "Studies on the interaction of H1 histone with superhelical DNA: characterization of the recognition and binding regions of H1 histones. The very lysine rich histone, H1, isolated from a variety of sources interacts preferentially with superhelical DNA compared to relaxed DNA duplexes. The nature of this specific interaction has been investigated by studying the ability of various purified fragments of H1 histone from calf thymus to recognize and bind superhelical DNA. The data suggest that the globular region of the H1 histone molecule (amino acid residues 72-106) is involved in the recognition of superhelical DNA. Thus, the H1 histone carboxy-terminal fragment, 72-212, resembles native H1 histone both quantitatively and qualitatively in its ability to discriminate between and bind to superhelical and relaxed DNA while the H1 histone carboxy-terminal fragment, residues 106-212, has lost this specificity, binding superhelical and relaxed DNA equally well. Furthermore, under conditions in which the globular region of the intact H1 histone has been unfolded, the molecule loses its ability to discriminate between superhelical and relaxed DNA, and binds both forms of DNA equally."}
{"id": "PMID:186762", "title": "The mechanism of the chemical synthesis of oligonucleotides and its synthetic consequences.", "content": "The data obtained mainly by pulsed NMR spectroscopy on phosphorus nuclei on the mechanism of the internucleotide phosphodiester (PDE) group formation are summarised. With arylsulphonyl chloride as condensing reagent monomeric nucleotide derivative B (nucleoside metaphosphate or its pyridinium adduct) is the highly reactive intermediate. In the presence of PDE groups in nucleoside or nucleotide component the significantly less reactive derivatives with trisubstituted pyrophosphoryl residues are formed both with arylsulphonyl chloride and dicyclohexylcarbodiimide (DCC). The reactive B form of nucleotide component may be obtained using greater excess of arylsulphonyl chloride with simultaneous convertion of PDE groups to tetrasubstituted pyrophosphates amenable to side reactions. The convertion of PDE groups to easily hydrolysable dicyclohexylurea derivatives by reaction with DCC is proposed to reversible blocking of PDE groups of nucleoside component. The B type derivatives of mononucleotides or oligonucleotides with blocked PDE groups seems to be the best nucleotide components.", "contents": "The mechanism of the chemical synthesis of oligonucleotides and its synthetic consequences. The data obtained mainly by pulsed NMR spectroscopy on phosphorus nuclei on the mechanism of the internucleotide phosphodiester (PDE) group formation are summarised. With arylsulphonyl chloride as condensing reagent monomeric nucleotide derivative B (nucleoside metaphosphate or its pyridinium adduct) is the highly reactive intermediate. In the presence of PDE groups in nucleoside or nucleotide component the significantly less reactive derivatives with trisubstituted pyrophosphoryl residues are formed both with arylsulphonyl chloride and dicyclohexylcarbodiimide (DCC). The reactive B form of nucleotide component may be obtained using greater excess of arylsulphonyl chloride with simultaneous convertion of PDE groups to tetrasubstituted pyrophosphates amenable to side reactions. The convertion of PDE groups to easily hydrolysable dicyclohexylurea derivatives by reaction with DCC is proposed to reversible blocking of PDE groups of nucleoside component. The B type derivatives of mononucleotides or oligonucleotides with blocked PDE groups seems to be the best nucleotide components."}
{"id": "PMID:186763", "title": "Absence of 5' terminal capping in encephalomyocarditis virus RNA.", "content": "The nature of the 5' terminus of encephalomyocarditis (EMC) virion RNA has been investigated. We have failed to detect any capped products or nucleoside polyphosphates arising upon complete digestion of the RNA with T1, T2, and pancreatic ribonucleases, and it would therefore appear that the 5' terminus of EMC virus RNA is not phosphorylated and not capped with m7G. EMC virions do contain, however, large amounts of all four 5'-monosubstituted nucleoside triphosphates (4.2M pppG; 16.4M pppA; 3.OM pppU and 2.5M pppC), of which at least a proportion (about 15-20%) appear to remain bound to fully denatured RNA in the presence of divalent cations.", "contents": "Absence of 5' terminal capping in encephalomyocarditis virus RNA. The nature of the 5' terminus of encephalomyocarditis (EMC) virion RNA has been investigated. We have failed to detect any capped products or nucleoside polyphosphates arising upon complete digestion of the RNA with T1, T2, and pancreatic ribonucleases, and it would therefore appear that the 5' terminus of EMC virus RNA is not phosphorylated and not capped with m7G. EMC virions do contain, however, large amounts of all four 5'-monosubstituted nucleoside triphosphates (4.2M pppG; 16.4M pppA; 3.OM pppU and 2.5M pppC), of which at least a proportion (about 15-20%) appear to remain bound to fully denatured RNA in the presence of divalent cations."}
{"id": "PMID:186764", "title": "Size and location of poly (A) in encephalomyocarditis virus RNA.", "content": "Encephalomyocarditis (EMC) virus RNA contains a covalently bound sequence of polyriboadenylic acid (poly(A). This was determined by two-dimensional gel electrophoresis of complete T1 and pancreatic RNase digests of formamidesucrose gradient-purified RNA and subsequent analysis of the product by alkaline hydrolysis. The size of the EMC virus genomic poly(A) sequence was estimated by formamide-polyacrylamide gel electrophoresis of the RNase-resistant product, or by [3H-]poly(U) hybridization to freshly purified virion RNA, to be, on average, 40 nucleotides in length. The evidence obtained from [3H-]isoniazid labelling and other experiments would indicate that the poly(A) sequence is located at the 3'-terminus of EMC virus RNA.", "contents": "Size and location of poly (A) in encephalomyocarditis virus RNA. Encephalomyocarditis (EMC) virus RNA contains a covalently bound sequence of polyriboadenylic acid (poly(A). This was determined by two-dimensional gel electrophoresis of complete T1 and pancreatic RNase digests of formamidesucrose gradient-purified RNA and subsequent analysis of the product by alkaline hydrolysis. The size of the EMC virus genomic poly(A) sequence was estimated by formamide-polyacrylamide gel electrophoresis of the RNase-resistant product, or by [3H-]poly(U) hybridization to freshly purified virion RNA, to be, on average, 40 nucleotides in length. The evidence obtained from [3H-]isoniazid labelling and other experiments would indicate that the poly(A) sequence is located at the 3'-terminus of EMC virus RNA."}
{"id": "PMID:186769", "title": "The effect of administered corticosteroids on the growth of children.", "content": "The growth-inhibiting effect of exogenous corticosteroids has been reported in many papers. Most of them have concerned the clinical problems of asthma and rheumatoid arthritis but it is probable that the underlying disease is relatively unimportant in determining the effect on growth. Steroid therapy on alternate days seems to produce less undesirable effects than steroid treatment every day and corticotrophin may be preferable. Although the mechanisms are uncertain it seems likely that the action is peripheral and certainly exogenous growth hormone does not prevent the steroid effect. A minimal dosage of corticosteroids should always be used in replacement therapy for hypopituitarism.", "contents": "The effect of administered corticosteroids on the growth of children. The growth-inhibiting effect of exogenous corticosteroids has been reported in many papers. Most of them have concerned the clinical problems of asthma and rheumatoid arthritis but it is probable that the underlying disease is relatively unimportant in determining the effect on growth. Steroid therapy on alternate days seems to produce less undesirable effects than steroid treatment every day and corticotrophin may be preferable. Although the mechanisms are uncertain it seems likely that the action is peripheral and certainly exogenous growth hormone does not prevent the steroid effect. A minimal dosage of corticosteroids should always be used in replacement therapy for hypopituitarism."}
{"id": "PMID:186770", "title": "Immunological and compositional patterns of lipoproteins in chicken (Gallus domesticus) plasma.", "content": "Immunological and compositional patterns of plasma lipoproteins in the laying and nonlaying hen (Gallus domesticus) and rooster plasmas were compared. Hen plasma contained three immunologically distinct lipoproteins: very low density (CLDL) and low density (LDL); high density (HDL); and lipovitellin (LV). Rooster plasma contained VLDL and LDL; and HDL. Laying hen plasma in comparison to the other groups of birds contained a high content of VLDL and LV. The plasma lipoprotein pattern of nonlaying hens and roosters were similar except for the relatively high content of LDL and the presence of low levels of LV in nonlaying hen plasma. In general, triglyceride, phospholipid and cholesterol contents were similar for each lipoprotein class in laying hen, nonlaying hen and rooster plasma.", "contents": "Immunological and compositional patterns of lipoproteins in chicken (Gallus domesticus) plasma. Immunological and compositional patterns of plasma lipoproteins in the laying and nonlaying hen (Gallus domesticus) and rooster plasmas were compared. Hen plasma contained three immunologically distinct lipoproteins: very low density (CLDL) and low density (LDL); high density (HDL); and lipovitellin (LV). Rooster plasma contained VLDL and LDL; and HDL. Laying hen plasma in comparison to the other groups of birds contained a high content of VLDL and LV. The plasma lipoprotein pattern of nonlaying hens and roosters were similar except for the relatively high content of LDL and the presence of low levels of LV in nonlaying hen plasma. In general, triglyceride, phospholipid and cholesterol contents were similar for each lipoprotein class in laying hen, nonlaying hen and rooster plasma."}
{"id": "PMID:186771", "title": "Horizontal transmission of turkey herpesvirus to chickens. 5. Airborne transmission between chickens.", "content": "Airborne transmission of turkey herpesvirus (HVT) between chickens was studied in two trials using an experimental line of White Leghorns. HVT either did not spread or spread poorly to chickens that had been exposed for 8 weeks to the exhaust air from a cage containing donor chickens inoculated with HVT at 8 weeks of age. There was no airborne transmission of HVT to chickens that had been exposed for 4 weeks. This study indicated a possible by an infrequent spread of HVT between chickens via airborne route.", "contents": "Horizontal transmission of turkey herpesvirus to chickens. 5. Airborne transmission between chickens. Airborne transmission of turkey herpesvirus (HVT) between chickens was studied in two trials using an experimental line of White Leghorns. HVT either did not spread or spread poorly to chickens that had been exposed for 8 weeks to the exhaust air from a cage containing donor chickens inoculated with HVT at 8 weeks of age. There was no airborne transmission of HVT to chickens that had been exposed for 4 weeks. This study indicated a possible by an infrequent spread of HVT between chickens via airborne route."}
{"id": "PMID:186767", "title": "Renal pathomorphology and histochemistry in dog after hemodilution as well as after administration of full blood in extracorporeal circulation in dog.", "content": "Dog kidneys were studied morphologically and histochemically after hemodilution to a 10--20% hematocrict value and transfusion of whole blood under conditions of extracorporeal circulation ensuring constant (linear) flow. Marked interstitial edema in the dog kidneys after hemodilution was the most pronounced alteration, attributed to disorders in the capillary circulation depending upon the apparatus employed. This conclusion was supported by similar changes in animals subjected to various degrees of hemodilution. Widening of the glomerular space and compression of renal tubules were the direct consequences of interstitial edema. Histochemical reactions revealed damage of the cell membranes. Swelling of the ergastoplasm and lysosomes was interpreted as secondary to disorders in circulation of tissue fluid. The least pronounced changes concerned the mitochondria. After extracorporeal circulation with whole blood, thrombi and fat emboli were observed in the blood vessels of the renal glomeruli, attributable to damage of blood in the extracorporeal circulation apparatus.", "contents": "Renal pathomorphology and histochemistry in dog after hemodilution as well as after administration of full blood in extracorporeal circulation in dog. Dog kidneys were studied morphologically and histochemically after hemodilution to a 10--20% hematocrict value and transfusion of whole blood under conditions of extracorporeal circulation ensuring constant (linear) flow. Marked interstitial edema in the dog kidneys after hemodilution was the most pronounced alteration, attributed to disorders in the capillary circulation depending upon the apparatus employed. This conclusion was supported by similar changes in animals subjected to various degrees of hemodilution. Widening of the glomerular space and compression of renal tubules were the direct consequences of interstitial edema. Histochemical reactions revealed damage of the cell membranes. Swelling of the ergastoplasm and lysosomes was interpreted as secondary to disorders in circulation of tissue fluid. The least pronounced changes concerned the mitochondria. After extracorporeal circulation with whole blood, thrombi and fat emboli were observed in the blood vessels of the renal glomeruli, attributable to damage of blood in the extracorporeal circulation apparatus."}
{"id": "PMID:186768", "title": "Aldosteronemia in patients with acute renal failure.", "content": "In 19 patients with acute renal failure the plasma renin activity and aldosterone were determined in the phase of anuria and oliguria. A highly increased plasma renin activity was found while aldosteronemia was only moderately raised. No significant correlation was demonstrated between plasma renin activity and aldosterone while a negative correlation was found between aldosteronemia and plasma sodium and bicarbonates concentrations. Lack of significant correlation between plasma renin activity and aldosteronemia in cases of acute renal failure suggests that factors other than renin participate in the regulation of aldosterone secretion in these patients.", "contents": "Aldosteronemia in patients with acute renal failure. In 19 patients with acute renal failure the plasma renin activity and aldosterone were determined in the phase of anuria and oliguria. A highly increased plasma renin activity was found while aldosteronemia was only moderately raised. No significant correlation was demonstrated between plasma renin activity and aldosterone while a negative correlation was found between aldosteronemia and plasma sodium and bicarbonates concentrations. Lack of significant correlation between plasma renin activity and aldosteronemia in cases of acute renal failure suggests that factors other than renin participate in the regulation of aldosterone secretion in these patients."}
{"id": "PMID:186772", "title": "[Activators of phospholipase D].", "content": "The activation of phospholipase D from cotton seeds by diethyl ester, sodium dodecyl sulphate and silica gel during egg lecithin hydrolysis was investigated. In the presence of silica gel the enzymic reaction developed without calcium ions. The data were accumulated indicating that the main characteristics of phospholipase D obtained from the in vitro study of the enzymic hydrolysis of phospholipids depended at large on the activator applied.", "contents": "[Activators of phospholipase D]. The activation of phospholipase D from cotton seeds by diethyl ester, sodium dodecyl sulphate and silica gel during egg lecithin hydrolysis was investigated. In the presence of silica gel the enzymic reaction developed without calcium ions. The data were accumulated indicating that the main characteristics of phospholipase D obtained from the in vitro study of the enzymic hydrolysis of phospholipids depended at large on the activator applied."}
{"id": "PMID:186774", "title": "Biphasic stimulation of polyamine biosynthesis in primary mouse kidney cells by infection with polyoma virus:uncoupling from DNA and rRNA synthesis.", "content": "Infection of primary cultures of mouse kidney cells with polyoma virus causes a biphasic increase in the activities of L-ornithine decarboxylase (ODC; L-ornithine carboxy-lyase; EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (SAMD; S-adenoxyl-L-methionine carboxy-lyase; EC 4.1.50), as well as in the level of the polyamines putrescine, spermidine, and spermine. An early peak occurs during the period when early viral mRNA is synthesized and prior to the onset of virus-induced synthesis of host cell DNA. A late peak coincides in time with the maximum rate of virus-induced synthesis of cellular DNA. A similar biphasic stimulation of polyamine synthesis is induced even when DNA synthesis is prevented by 5-fluorodeoxyuridine. Actinomycin D (AMD) in a dose that inhibits rRNA synthesis causes no inhibition of ODC or SAMD. In a dose that inhibits mRNA synthesis as well, short-term AMD treatment causes \"superinduction\" of ODC but inhibition of SAMD. Prolonged treatment with the high dose of AMD inhibits ODC as well, indicating that late ODC activity may be dependent on mRNA synthesized during early infection. Cycloheximide effectively obliterates the ODC and SAMD activities during the entire infectious cycle. Uncoupling from DNA and rRNA synthesis suggests that polyamine synthesis is regulated independently of these events. The experiments with AMD and cycloheximide suggest that the formation of ODC is subject to post-transcriptional control, whereas that of SAMD is regulated primarily at the transcriptional level.", "contents": "Biphasic stimulation of polyamine biosynthesis in primary mouse kidney cells by infection with polyoma virus:uncoupling from DNA and rRNA synthesis. Infection of primary cultures of mouse kidney cells with polyoma virus causes a biphasic increase in the activities of L-ornithine decarboxylase (ODC; L-ornithine carboxy-lyase; EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (SAMD; S-adenoxyl-L-methionine carboxy-lyase; EC 4.1.50), as well as in the level of the polyamines putrescine, spermidine, and spermine. An early peak occurs during the period when early viral mRNA is synthesized and prior to the onset of virus-induced synthesis of host cell DNA. A late peak coincides in time with the maximum rate of virus-induced synthesis of cellular DNA. A similar biphasic stimulation of polyamine synthesis is induced even when DNA synthesis is prevented by 5-fluorodeoxyuridine. Actinomycin D (AMD) in a dose that inhibits rRNA synthesis causes no inhibition of ODC or SAMD. In a dose that inhibits mRNA synthesis as well, short-term AMD treatment causes \"superinduction\" of ODC but inhibition of SAMD. Prolonged treatment with the high dose of AMD inhibits ODC as well, indicating that late ODC activity may be dependent on mRNA synthesized during early infection. Cycloheximide effectively obliterates the ODC and SAMD activities during the entire infectious cycle. Uncoupling from DNA and rRNA synthesis suggests that polyamine synthesis is regulated independently of these events. The experiments with AMD and cycloheximide suggest that the formation of ODC is subject to post-transcriptional control, whereas that of SAMD is regulated primarily at the transcriptional level."}
{"id": "PMID:186775", "title": "DNA gyrase: an enzyme that introduces superhelical turns into DNA.", "content": "Relaxed closed-circular DNA is converted to negatively supercoiled DNA by DNA gyrase. This enzyme has been purified from Escherichia coli cells. The reaction requires ATP and Mg++ and is stimulated by spermidine. The enzyme acts equally well on relaxed closed-circular colicin E1, phage lambda, and simian virus 40 DNA. The final superhelix density of the DNA can be considerably greater than that found in intracellularly supercoiled DNA.", "contents": "DNA gyrase: an enzyme that introduces superhelical turns into DNA. Relaxed closed-circular DNA is converted to negatively supercoiled DNA by DNA gyrase. This enzyme has been purified from Escherichia coli cells. The reaction requires ATP and Mg++ and is stimulated by spermidine. The enzyme acts equally well on relaxed closed-circular colicin E1, phage lambda, and simian virus 40 DNA. The final superhelix density of the DNA can be considerably greater than that found in intracellularly supercoiled DNA."}
{"id": "PMID:186776", "title": "Dose-dependent depletion of nuclear receptors by L-triiodothyronine: evidence for a role in induction of growth hormone synthesis in cultured GH1 cells.", "content": "The relationship between the binding of L-triiodothyronine (T3) to nuclear receptors and the induction of growth hormone synthesis was examined in cultured GH1 cells, a rat pituitary cell line. After 24 hr, T3 induced a maximal 4-fold increase in the rate of growth hormone wynthesis; the T3 concentration that induced a half-maximal increase was 0.22 nM. The biologic dose-response curve was shifted to the left of the receptor occupancy curve (Kd = 0.5 nM) by a factor of approximately 2 when receptor binding was examined for 4 hr but showed a significantly closer agreement when examined for the same 24-hr period as the biologic response. This shift in the fractional occupancy curve is not due to further equilibration but occurs as a result of a time- and dose-dependent depletion of the nuclear receptor by T3.", "contents": "Dose-dependent depletion of nuclear receptors by L-triiodothyronine: evidence for a role in induction of growth hormone synthesis in cultured GH1 cells. The relationship between the binding of L-triiodothyronine (T3) to nuclear receptors and the induction of growth hormone synthesis was examined in cultured GH1 cells, a rat pituitary cell line. After 24 hr, T3 induced a maximal 4-fold increase in the rate of growth hormone wynthesis; the T3 concentration that induced a half-maximal increase was 0.22 nM. The biologic dose-response curve was shifted to the left of the receptor occupancy curve (Kd = 0.5 nM) by a factor of approximately 2 when receptor binding was examined for 4 hr but showed a significantly closer agreement when examined for the same 24-hr period as the biologic response. This shift in the fractional occupancy curve is not due to further equilibration but occurs as a result of a time- and dose-dependent depletion of the nuclear receptor by T3."}
{"id": "PMID:186777", "title": "Regulation of dopamine stimulation of striatal adenylate cyclase by an endogenous Ca++ -binding protein.", "content": "Membranes of rat caudate nucleus contain a dopamine-dependent adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and a Ca++ binding protein that activates phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17). This activator can be released from the membranes by a phosphorylation with a 3':5' cAMP-dependent protein kinase (ATP-protein phosphotransferase, EC 2.7.1.37). Under the conditions of membrane phosphorylation and activator release, dopamine fails to activate striatal adenylate cyclase. The basal activity of this enzyme is not decreased by the release of the protein activator but the activation by NaF is reduced. Adenylate cyclase is not phosphorylated when the dopamine activation is blocked after the release of the activator, but other membrane proteins are phosphorylated. It is postulated that the endogenous protein stored in striatal membranes can regulate the intracellular concentration of cAMP by an activation of adenylate cyclase while stored in striatal membrane, and by an activation of phosphodiesterase when released into the cytosol after membrane phosphorylation.", "contents": "Regulation of dopamine stimulation of striatal adenylate cyclase by an endogenous Ca++ -binding protein. Membranes of rat caudate nucleus contain a dopamine-dependent adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and a Ca++ binding protein that activates phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17). This activator can be released from the membranes by a phosphorylation with a 3':5' cAMP-dependent protein kinase (ATP-protein phosphotransferase, EC 2.7.1.37). Under the conditions of membrane phosphorylation and activator release, dopamine fails to activate striatal adenylate cyclase. The basal activity of this enzyme is not decreased by the release of the protein activator but the activation by NaF is reduced. Adenylate cyclase is not phosphorylated when the dopamine activation is blocked after the release of the activator, but other membrane proteins are phosphorylated. It is postulated that the endogenous protein stored in striatal membranes can regulate the intracellular concentration of cAMP by an activation of adenylate cyclase while stored in striatal membrane, and by an activation of phosphodiesterase when released into the cytosol after membrane phosphorylation."}
{"id": "PMID:186778", "title": "Purification and characterization of 3':5'-cyclic GMP-dependent protein kinase.", "content": "Guanosine 3':5'-cyclic monophosphate (cGMP)-dependent protein kinase has been purified to homogeneity from bovine lung by affinity chromatography and characterized. Partially purified protein kinase, specifically activated by low concentrations of cGMP (22 NM), was adsorbed onto 8-(2-aminoethyl)-amino-adenosine 3':5'-cyclic monophosphate-Sepharose. After washing to remove nonspecific proteins, cGMP-dependent protein kinase was specifically eluted by 0.1 mM cGMP. The purified protein contained cGMP-dependent protein kinase and specific cGMP binding activities. Purification of the holoenzyme was possible because subunit dissociation does not occur upon cyclic nucleotide binding. cGMP-dependent protein kinase holoenzyme has an apparent molecular weight of 150,000 as determined by glycerol density gradient sedimentation. On sodium dodecyl sulfate/polyacrylamide gel electrophoresis, a single protein band of 71,000 molecular weight was observed that suggested the holoenzyme is a dimer composed of subunits of identical molecular weight. cGMP-dependent protein kinase required high concentrations of Mg+2 for optimal activity; a heat-stable protein kinase modulator which inhibited adenosine 3':5'-cyclic monophosphate-dependent protein kinase activity had no effect on the activity of purified cGMP-dependent protein kinase.", "contents": "Purification and characterization of 3':5'-cyclic GMP-dependent protein kinase. Guanosine 3':5'-cyclic monophosphate (cGMP)-dependent protein kinase has been purified to homogeneity from bovine lung by affinity chromatography and characterized. Partially purified protein kinase, specifically activated by low concentrations of cGMP (22 NM), was adsorbed onto 8-(2-aminoethyl)-amino-adenosine 3':5'-cyclic monophosphate-Sepharose. After washing to remove nonspecific proteins, cGMP-dependent protein kinase was specifically eluted by 0.1 mM cGMP. The purified protein contained cGMP-dependent protein kinase and specific cGMP binding activities. Purification of the holoenzyme was possible because subunit dissociation does not occur upon cyclic nucleotide binding. cGMP-dependent protein kinase holoenzyme has an apparent molecular weight of 150,000 as determined by glycerol density gradient sedimentation. On sodium dodecyl sulfate/polyacrylamide gel electrophoresis, a single protein band of 71,000 molecular weight was observed that suggested the holoenzyme is a dimer composed of subunits of identical molecular weight. cGMP-dependent protein kinase required high concentrations of Mg+2 for optimal activity; a heat-stable protein kinase modulator which inhibited adenosine 3':5'-cyclic monophosphate-dependent protein kinase activity had no effect on the activity of purified cGMP-dependent protein kinase."}
{"id": "PMID:186779", "title": "Negative homotropic cooperativity and affinity heterogeneity: preparation of yeast glyceraldehyde-3-phosphate dehydrogenase with maximal affinity homogeneity.", "content": "A three-step procedure including affinity chromatography on NAD+-azobenzamidopropyl-Sepharose has been designed for the purification of yeast glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12] with maximized specific activity and maximized homogeneity with respect to affinity for the coenzyme, NAD+. Binding isotherms allow the analysis of cooperativity patterns that disclose both the average ligand affinity in the system and the distribution of ligands among the sites, only for systems with complete affinity homogeneity. The presence of affinity heterogeneity, resulting from multiple oligomeric species differing only in their affinity for coenzyme, gives rise to isotherms which falsely manifest apparent negative cooperativity. A method for distinguishing negative homotropic cooperativity from affinity heterogeneity is suggested.", "contents": "Negative homotropic cooperativity and affinity heterogeneity: preparation of yeast glyceraldehyde-3-phosphate dehydrogenase with maximal affinity homogeneity. A three-step procedure including affinity chromatography on NAD+-azobenzamidopropyl-Sepharose has been designed for the purification of yeast glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12] with maximized specific activity and maximized homogeneity with respect to affinity for the coenzyme, NAD+. Binding isotherms allow the analysis of cooperativity patterns that disclose both the average ligand affinity in the system and the distribution of ligands among the sites, only for systems with complete affinity homogeneity. The presence of affinity heterogeneity, resulting from multiple oligomeric species differing only in their affinity for coenzyme, gives rise to isotherms which falsely manifest apparent negative cooperativity. A method for distinguishing negative homotropic cooperativity from affinity heterogeneity is suggested."}
{"id": "PMID:186780", "title": "Regulation of mitochondrial protein synthesis by cytoplasmic proteins.", "content": "Isolated yeast mitochondria, which synthesize identifiable polypeptides identical to those made in vivo, have been used in an invitro system to study cytoplasmic control of mitochondrial protein synthesis. It has been found that protein synthesis in isolated mitochondria is dependent on an endogenous pool of cytoplasmically synthesized proteins present within mitochondria at the time of isolation, that protein synthesis ceases apparently when this pool of proteins is depleted, and that a cytoplasmic extract can restore protein synthesis in depleted mitochondria. By use of depleted mitochondria to assay for stimulatory factors it has been found that the bulk of the stimulatory activity in the cytoplasm is of a protein nature and resides predominantly in the postpolysomal supernatant. At least one cytoplasmic stimulatory protein appears to exert a specific effect on the synthesis of subunits I-III of cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1).", "contents": "Regulation of mitochondrial protein synthesis by cytoplasmic proteins. Isolated yeast mitochondria, which synthesize identifiable polypeptides identical to those made in vivo, have been used in an invitro system to study cytoplasmic control of mitochondrial protein synthesis. It has been found that protein synthesis in isolated mitochondria is dependent on an endogenous pool of cytoplasmically synthesized proteins present within mitochondria at the time of isolation, that protein synthesis ceases apparently when this pool of proteins is depleted, and that a cytoplasmic extract can restore protein synthesis in depleted mitochondria. By use of depleted mitochondria to assay for stimulatory factors it has been found that the bulk of the stimulatory activity in the cytoplasm is of a protein nature and resides predominantly in the postpolysomal supernatant. At least one cytoplasmic stimulatory protein appears to exert a specific effect on the synthesis of subunits I-III of cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1)."}
{"id": "PMID:186781", "title": "Mapping oligonucleotides of Rous sarcoma virus RNA that segregate with polymerase and group-specific antigen markers in recombinants.", "content": "The RNase-T1-resistant oligonucleotides of two Prague Rous sarcoma viruses with temperature-sensitive (ts) DNA polymerases (DNA nucleotidyltransferases), termed ts LA 337 and 335 of one leukosis virus, RAV-6, and 20 of their recombinant progeny have been mapped relative to the 3' poly (A) terminus of the viral RNA. The resulting oligonucleotide maps have been ocrrelated with markers of the four known viral genetic elements encoded in the RNA of 10,000 nucleotides. In accord with previous results recombinant RNAs contained (i) oligonucleotides characteristic of the src gene, coding for sarcoma formation, between the poly(A) end and 2000 nucleotides and (ii) olignucleotides characteristic of the env gene, coding for the envelope glycoprotein, between 2500 and 5000 nucleo tides from the poly(A) end. (iii) A cluster of four oligonucleotides that mapped between 6000 and 8000 nucleotides from the 3' poly(A) end of each RNA was shared by both parental viruses and all recombinants. Since all other map segments of our recombinants failed to segregate with the ts- or wild-type markers of the parental DNA polymerase gene (pol), it was concluded that the ts pol lesion maps in this RNA segment. (iv) The 5' segment of each recombinant RNA contained a cluster of four to five oligonucleotides whose parental origin correlated with an electrophoretic marker of one of the parental virion proteins, p27, a major product of the viral gag gene. The gene order 5'-gag-pol-env-src-poly(A) is consistent with our data.", "contents": "Mapping oligonucleotides of Rous sarcoma virus RNA that segregate with polymerase and group-specific antigen markers in recombinants. The RNase-T1-resistant oligonucleotides of two Prague Rous sarcoma viruses with temperature-sensitive (ts) DNA polymerases (DNA nucleotidyltransferases), termed ts LA 337 and 335 of one leukosis virus, RAV-6, and 20 of their recombinant progeny have been mapped relative to the 3' poly (A) terminus of the viral RNA. The resulting oligonucleotide maps have been ocrrelated with markers of the four known viral genetic elements encoded in the RNA of 10,000 nucleotides. In accord with previous results recombinant RNAs contained (i) oligonucleotides characteristic of the src gene, coding for sarcoma formation, between the poly(A) end and 2000 nucleotides and (ii) olignucleotides characteristic of the env gene, coding for the envelope glycoprotein, between 2500 and 5000 nucleo tides from the poly(A) end. (iii) A cluster of four oligonucleotides that mapped between 6000 and 8000 nucleotides from the 3' poly(A) end of each RNA was shared by both parental viruses and all recombinants. Since all other map segments of our recombinants failed to segregate with the ts- or wild-type markers of the parental DNA polymerase gene (pol), it was concluded that the ts pol lesion maps in this RNA segment. (iv) The 5' segment of each recombinant RNA contained a cluster of four to five oligonucleotides whose parental origin correlated with an electrophoretic marker of one of the parental virion proteins, p27, a major product of the viral gag gene. The gene order 5'-gag-pol-env-src-poly(A) is consistent with our data."}
{"id": "PMID:186782", "title": "Evidence for specific recognition sites mediating clearance of lysosomal enzymes in vivo.", "content": "A study of the clearance of liver lysosomal enzymes was carried out in the rat. Purified rat liver lysosomal beta-D-glucuronidase (EC 3.2.1.31), N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), alpha-L-fucosidase (EC 3.2.1.51), and alpha-D-mannosidase (EC 3.2.1.24), as well as rat preputial gland beta-glucuronidase, were infused intravenously into anesthetized rats. All of the enzymes were rapidly cleared from the circulation. Sodium periodate oxidation of lysosomal beta-glucuronidase resulted in a near abolition of rapid clearance, a reduction in concanavilin-A-Sepharose binding, and a reduction in neutral sugar content, accompanied by alteration in isoelectric focusing properties. Similarly, periodate oxidation of lysosomal N-acetyl-beta-D-glucosaminidase resulted in a loss of the rapid clearance property. These results suggest that specific recognition sites occur on lysosomal hydrolases which mediate clearance following intravenous injection, and that these sites involve the carbohydrate portions of the enzymes.", "contents": "Evidence for specific recognition sites mediating clearance of lysosomal enzymes in vivo. A study of the clearance of liver lysosomal enzymes was carried out in the rat. Purified rat liver lysosomal beta-D-glucuronidase (EC 3.2.1.31), N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), alpha-L-fucosidase (EC 3.2.1.51), and alpha-D-mannosidase (EC 3.2.1.24), as well as rat preputial gland beta-glucuronidase, were infused intravenously into anesthetized rats. All of the enzymes were rapidly cleared from the circulation. Sodium periodate oxidation of lysosomal beta-glucuronidase resulted in a near abolition of rapid clearance, a reduction in concanavilin-A-Sepharose binding, and a reduction in neutral sugar content, accompanied by alteration in isoelectric focusing properties. Similarly, periodate oxidation of lysosomal N-acetyl-beta-D-glucosaminidase resulted in a loss of the rapid clearance property. These results suggest that specific recognition sites occur on lysosomal hydrolases which mediate clearance following intravenous injection, and that these sites involve the carbohydrate portions of the enzymes."}
{"id": "PMID:186783", "title": "Relationship of gangliosides to the structure and function of thyrotropin receptors: their absence on plasma membranes of a thyroid tumor defective in thyrotropin receptor activity.", "content": "Plasma membranes derived from rat thyroid tumor (1-8R) which is unresponsive to thyrotropin but is responsive to dibutyryl adenosine 3':5'-cyclic monophosphate bind less than 20% of the [125I] thyrotropin which can be bound to plasma membranes from normal rat thyroids under conditions which optimize tumor membrane binding relative to normal thyroid membranes. In addition, the binding is different from thyrotropin binding to normal thyroid membranes both in its altered sensitivity to changes in hydrogen ion concentration and in a decreased sensitivity to competition by unlabeled thyrotropin. This reduced capacity to bind [125I] thyrotropin cannot be attributed to degradation of the hormone by membrane-associated proteases. Although the supernatant phase of the thyroid tumor homogenates contains a soluble component which inhibits [125I] thyrotropin binding to thyrotropin receptors on plasma membranes, its level is the same as in homogenates of normal thyroid tissue. Trypsin digestion does not expose thyrotropin receptors in a manner analogous to that seen in normal thyroid tissue. The major ganglioside in the tumor membranes is N-acetylneuraminylgalactosylglucosylceramide and the membranes lack the N-acetylgalactosaminyltransferase required for the synthesis of more complex gangliosides. In contrast, the normal rat thyroid membranes contain more complex gangliosides such as galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide and N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosyl ceramide as well as the glycosyltransferase activities required for their syntheses. Galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide can also be detected in normal membranes, but not in tumor membranes, by selective labeling with galactose oxidase (D-galactose: oxygen 6-oxidoreductase, EC 1.1.3.9) and [3H] sodium borohydride. These results support the hypothesis that gangliosides are important structural or functional components of thyrotropin receptors on thyroid plasma membranes.", "contents": "Relationship of gangliosides to the structure and function of thyrotropin receptors: their absence on plasma membranes of a thyroid tumor defective in thyrotropin receptor activity. Plasma membranes derived from rat thyroid tumor (1-8R) which is unresponsive to thyrotropin but is responsive to dibutyryl adenosine 3':5'-cyclic monophosphate bind less than 20% of the [125I] thyrotropin which can be bound to plasma membranes from normal rat thyroids under conditions which optimize tumor membrane binding relative to normal thyroid membranes. In addition, the binding is different from thyrotropin binding to normal thyroid membranes both in its altered sensitivity to changes in hydrogen ion concentration and in a decreased sensitivity to competition by unlabeled thyrotropin. This reduced capacity to bind [125I] thyrotropin cannot be attributed to degradation of the hormone by membrane-associated proteases. Although the supernatant phase of the thyroid tumor homogenates contains a soluble component which inhibits [125I] thyrotropin binding to thyrotropin receptors on plasma membranes, its level is the same as in homogenates of normal thyroid tissue. Trypsin digestion does not expose thyrotropin receptors in a manner analogous to that seen in normal thyroid tissue. The major ganglioside in the tumor membranes is N-acetylneuraminylgalactosylglucosylceramide and the membranes lack the N-acetylgalactosaminyltransferase required for the synthesis of more complex gangliosides. In contrast, the normal rat thyroid membranes contain more complex gangliosides such as galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide and N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosyl ceramide as well as the glycosyltransferase activities required for their syntheses. Galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide can also be detected in normal membranes, but not in tumor membranes, by selective labeling with galactose oxidase (D-galactose: oxygen 6-oxidoreductase, EC 1.1.3.9) and [3H] sodium borohydride. These results support the hypothesis that gangliosides are important structural or functional components of thyrotropin receptors on thyroid plasma membranes."}
{"id": "PMID:186784", "title": "Changes in microfilament organization and surface topogrophy upon transformation of chick embryo fibroblasts with Rous sarcoma virus.", "content": "A series of morphological changes occurred when chick embryo fibroblasts infected with the NY68 mutant of Rous sarcoma virus were shifted from nonpermissive temperature (41degrees) to permissive temperature (37 degrees). We observed three distinct stages in cell morphology and surface topography that were correlated with a reduction in the organization and assembly of actin-containing microfilament bundles. Our observations suggest that control of microfilament organization and surface topography are responsive to the presence of a functioning transforming gene (src) product of Rous sarcoma virus.", "contents": "Changes in microfilament organization and surface topogrophy upon transformation of chick embryo fibroblasts with Rous sarcoma virus. A series of morphological changes occurred when chick embryo fibroblasts infected with the NY68 mutant of Rous sarcoma virus were shifted from nonpermissive temperature (41degrees) to permissive temperature (37 degrees). We observed three distinct stages in cell morphology and surface topography that were correlated with a reduction in the organization and assembly of actin-containing microfilament bundles. Our observations suggest that control of microfilament organization and surface topography are responsive to the presence of a functioning transforming gene (src) product of Rous sarcoma virus."}
{"id": "PMID:186785", "title": "Alterations in surface glycoproteins and level of sialyltransferase of cells transformed by a temperature-sensitive mutant of simian virus 40.", "content": "Mouse cells transformed by a temperature-sensitive mutant of simian virus 40 belonging to complementation group A lost their ability to regulate cell growth when grown at the permissive temperature (35 degrees) but showed the low saturation density of cell growth at the restrictive temperature (39.5 degrees) that is characteristic of normal cells in vitro. Biochemical analysis of the membranes of cells grown under the restrictive and the permissive conditions demonstrated no qualitative temperature-dependent differences either in neutral glycolipids or in acidic glycolipids of the cells. Plasma membrane glycoproteins labeled with radioactive glucosamine showed significantly different patterns on both polyacrylamide gel electrophoresis and electrofocusing. When the levels of glycoprotein glycosyltransferases of the cells were examined, the level of sialyltransferase (CMP-N-acetylneuraminytransferase,EC 2.4.99.1) of the cells grown at the restrictive temperature was low compared with that of cells grown at the permissive temperature. Our results indicate that the level of sialyltransferase is under the control of the gene A function of simian virus 40 and consequently is related to alterations in the cell surface glycoproteins.", "contents": "Alterations in surface glycoproteins and level of sialyltransferase of cells transformed by a temperature-sensitive mutant of simian virus 40. Mouse cells transformed by a temperature-sensitive mutant of simian virus 40 belonging to complementation group A lost their ability to regulate cell growth when grown at the permissive temperature (35 degrees) but showed the low saturation density of cell growth at the restrictive temperature (39.5 degrees) that is characteristic of normal cells in vitro. Biochemical analysis of the membranes of cells grown under the restrictive and the permissive conditions demonstrated no qualitative temperature-dependent differences either in neutral glycolipids or in acidic glycolipids of the cells. Plasma membrane glycoproteins labeled with radioactive glucosamine showed significantly different patterns on both polyacrylamide gel electrophoresis and electrofocusing. When the levels of glycoprotein glycosyltransferases of the cells were examined, the level of sialyltransferase (CMP-N-acetylneuraminytransferase,EC 2.4.99.1) of the cells grown at the restrictive temperature was low compared with that of cells grown at the permissive temperature. Our results indicate that the level of sialyltransferase is under the control of the gene A function of simian virus 40 and consequently is related to alterations in the cell surface glycoproteins."}
{"id": "PMID:186786", "title": "Quantitative studies of integration of murine leukemia virus after exogenous infection.", "content": "Using a [3H]DNA probe prepared from AKR murine leukemia virus, we determined the number of copies of the AKR virus genome integrated into the cellular DNA after exogenous infection of NIH mouse, AKR mouse, and rat cells in tissue culture. NIH mouse cells, which lack a portion of the viral genome (referred to as Gross-AKR specific sequences), incorporated three to four copies of these sequences per haploid genome. AKR cells, in which the Gross-AKR specific sequences are already present as three to four copies per haploid genome, did not shwo any distinct change in copy number after infection. Rat cells, which lack DNA sequences homologous to murine leukemia virus, incorporated one copy of the viral genome per haploid genome. It is inferred that the presence of viral sequences may affect the efficiency of integration of exogenous provirus, and that there may be a limit to the number of copies that can be inserted.", "contents": "Quantitative studies of integration of murine leukemia virus after exogenous infection. Using a [3H]DNA probe prepared from AKR murine leukemia virus, we determined the number of copies of the AKR virus genome integrated into the cellular DNA after exogenous infection of NIH mouse, AKR mouse, and rat cells in tissue culture. NIH mouse cells, which lack a portion of the viral genome (referred to as Gross-AKR specific sequences), incorporated three to four copies of these sequences per haploid genome. AKR cells, in which the Gross-AKR specific sequences are already present as three to four copies per haploid genome, did not shwo any distinct change in copy number after infection. Rat cells, which lack DNA sequences homologous to murine leukemia virus, incorporated one copy of the viral genome per haploid genome. It is inferred that the presence of viral sequences may affect the efficiency of integration of exogenous provirus, and that there may be a limit to the number of copies that can be inserted."}
{"id": "PMID:186787", "title": "Localization of gene functions in polyoma virus DNA.", "content": "Polyoma virus mutants of four functionally distinct groups have been mapped by the marker rescue technique using restriction enzyme fragments of wild-type viral DNA. Nontransforming host-range mutants map in the proximal part of the early region of the viral genome. The same DNA fragment that restores a normal host range also restores normal transforming ability to these mutants. ts-25D, a temperature-sensitive (ts)-a class mutant, maps in the distal part of the early region. ts-3 and ts-1260 map in the proximal and distal parts of the late region, respectively.", "contents": "Localization of gene functions in polyoma virus DNA. Polyoma virus mutants of four functionally distinct groups have been mapped by the marker rescue technique using restriction enzyme fragments of wild-type viral DNA. Nontransforming host-range mutants map in the proximal part of the early region of the viral genome. The same DNA fragment that restores a normal host range also restores normal transforming ability to these mutants. ts-25D, a temperature-sensitive (ts)-a class mutant, maps in the distal part of the early region. ts-3 and ts-1260 map in the proximal and distal parts of the late region, respectively."}
{"id": "PMID:186788", "title": "beta-Endorphin: cross tolerance to and cross physical dependence on morphine.", "content": "The effects of beta-endorphin on the antinociceptive responses and abrupt withdrawal jumping in morphine-dependent mice were studied. Mice were rendered morphine dependent by implantation of a morphine pellet (75 mg base) for 3 days. The analgesic response to beta-endorphin decreased after morphine pellet implantation, as evidenced by an eight-fold increase in the median antinociceptive dose of morphine was found. In small doses (0.09-0.17 mug per mouse), beta-endorphin suppressed abrupt withdrawal jumping. Met-enkephalin, even in high doses (200 mug per mouse), did not suppress abrupt withdrawal jumping.", "contents": "beta-Endorphin: cross tolerance to and cross physical dependence on morphine. The effects of beta-endorphin on the antinociceptive responses and abrupt withdrawal jumping in morphine-dependent mice were studied. Mice were rendered morphine dependent by implantation of a morphine pellet (75 mg base) for 3 days. The analgesic response to beta-endorphin decreased after morphine pellet implantation, as evidenced by an eight-fold increase in the median antinociceptive dose of morphine was found. In small doses (0.09-0.17 mug per mouse), beta-endorphin suppressed abrupt withdrawal jumping. Met-enkephalin, even in high doses (200 mug per mouse), did not suppress abrupt withdrawal jumping."}
{"id": "PMID:186789", "title": "Plasma levels of a viral protein as a diagnostic signal for the presence of tumor : the murine mammary tumor model.", "content": "We used the mouse mammary tumor and its associated virus (murine mammary tumor virus) to examine the possibility of using plasma levels of a viral protein (gp52, the glycoprotein of 52,000 molecular weight) as a diagnostic indicator of the presence of a solid tumor. The following features have emerged from our studies: (a) tumor-bearing animals show markedly elevated (100-1000 ng/ml) plasma levels of gp52 and the mean concentration increases with tumor size; (b) mammary tumor tissues located outside the mammary gland are also detected by the elevated plasma gp52; (c) low (2-10 ng/ml) plasma levels of gp52 are found in tumor-free mice, whether they are derived from strains characterized by high or low frequencies of spontaneous mammary tumors; (d) tumor-free lactating females exhibit the normally low levels of plasma gp52 despite the fact that their milk contains an average of 20,000 ng/ml of this antigen; (e) thus, high levels of plasma gp52 are found only in the presence of tumor and are not induced by either predisposition for the disease or by normal production of the antigen during lactation; (f) the circulatory clearance time of gp52 is sufficiently rapid to require continued replenishment to maintain the high levels observed in tumor-bearing animals, a feature implying that the gp52 concentration can be a responsive parameter of disease status. The information obtained suggests that plasma gp52 is a potentially useful and specific systemic indicator of the presence and extent of murine mammary neoplasia.", "contents": "Plasma levels of a viral protein as a diagnostic signal for the presence of tumor : the murine mammary tumor model. We used the mouse mammary tumor and its associated virus (murine mammary tumor virus) to examine the possibility of using plasma levels of a viral protein (gp52, the glycoprotein of 52,000 molecular weight) as a diagnostic indicator of the presence of a solid tumor. The following features have emerged from our studies: (a) tumor-bearing animals show markedly elevated (100-1000 ng/ml) plasma levels of gp52 and the mean concentration increases with tumor size; (b) mammary tumor tissues located outside the mammary gland are also detected by the elevated plasma gp52; (c) low (2-10 ng/ml) plasma levels of gp52 are found in tumor-free mice, whether they are derived from strains characterized by high or low frequencies of spontaneous mammary tumors; (d) tumor-free lactating females exhibit the normally low levels of plasma gp52 despite the fact that their milk contains an average of 20,000 ng/ml of this antigen; (e) thus, high levels of plasma gp52 are found only in the presence of tumor and are not induced by either predisposition for the disease or by normal production of the antigen during lactation; (f) the circulatory clearance time of gp52 is sufficiently rapid to require continued replenishment to maintain the high levels observed in tumor-bearing animals, a feature implying that the gp52 concentration can be a responsive parameter of disease status. The information obtained suggests that plasma gp52 is a potentially useful and specific systemic indicator of the presence and extent of murine mammary neoplasia."}
{"id": "PMID:186790", "title": "alpha-Adrenergic regulation of secretion of mouse saliva rich in nerve growth factor.", "content": "Nerve growth factor has been quantified by both bioassay and radial immunodiffusion in mouse saliva elicited by several secretagogues. The concentrations by bioassay of nerve growth factor in both epinephrine- and norepinephrine-induced saliva (3400 and 900 mug/ml, respectively) are higher than reported in any other source. In contrast, the concentrations of nerve growth factor in isoproterenol- and pilocarpine-induced saliva are relatively low (17 and 2 mug/ml, respectively). The specific activity of the salivary nerve growth factor was 41, 36, 2, and 0.6 mug/mg of protein in secretions elicited by epinephrine, norepinephrine, pilocarpine, and isoproterenol, respectively. Salivation after administration of either epinephrine or norepinephrine was completely inhibited by the alpha-adrenergic blocker, phenoxybenzamine. These results suggest that the release of saliva rich in nerve growth factor is primarily regulated through alpha-adrenergic receptors.", "contents": "alpha-Adrenergic regulation of secretion of mouse saliva rich in nerve growth factor. Nerve growth factor has been quantified by both bioassay and radial immunodiffusion in mouse saliva elicited by several secretagogues. The concentrations by bioassay of nerve growth factor in both epinephrine- and norepinephrine-induced saliva (3400 and 900 mug/ml, respectively) are higher than reported in any other source. In contrast, the concentrations of nerve growth factor in isoproterenol- and pilocarpine-induced saliva are relatively low (17 and 2 mug/ml, respectively). The specific activity of the salivary nerve growth factor was 41, 36, 2, and 0.6 mug/mg of protein in secretions elicited by epinephrine, norepinephrine, pilocarpine, and isoproterenol, respectively. Salivation after administration of either epinephrine or norepinephrine was completely inhibited by the alpha-adrenergic blocker, phenoxybenzamine. These results suggest that the release of saliva rich in nerve growth factor is primarily regulated through alpha-adrenergic receptors."}
{"id": "PMID:186791", "title": "The opiate receptor: a model explaining structure-activity relationships of opiate agonists and antagonists.", "content": "A model of the opiate receptor is proposed which explains structure-activity relationships of opiate drugs, including (i) the unique potency of certain opiates such as etonitazene, fentanyl, phenazocine, and oripavines; (ii) the role of N-allyl substituents in conferring antagonist properties; and (iii) chemical features that afford \"pure\" antagonists. The model indicates mlecular mechanisms for interconversion of the opiate receptor between respective states that bind agonists or antagonists with high affinity.", "contents": "The opiate receptor: a model explaining structure-activity relationships of opiate agonists and antagonists. A model of the opiate receptor is proposed which explains structure-activity relationships of opiate drugs, including (i) the unique potency of certain opiates such as etonitazene, fentanyl, phenazocine, and oripavines; (ii) the role of N-allyl substituents in conferring antagonist properties; and (iii) chemical features that afford \"pure\" antagonists. The model indicates mlecular mechanisms for interconversion of the opiate receptor between respective states that bind agonists or antagonists with high affinity."}
{"id": "PMID:186792", "title": "Chemical transmission between rat sympathetic neurons and cardiac myocytes developing in microcultures: evidence for cholinergic, adrenergic, and dual-function neurons.", "content": "Electrophysiological studies were made on microcultures (300-500 mum in diameter) in which solitary sympathetic principal neurons from newborn rats grew on previously dissociated rat heart cells. Some neurons inhibited,some excited, and others first inhibited and then excited the cardiac myocytes. Application of drugs provided evidence for secretion of acetylcholine by the first group, catecholamines by the second, and both acetylcholine and catecholamines by the third. Solitary neurons which inhibited themyocytes usually excited themselves at nicotinic synapses (autapses).", "contents": "Chemical transmission between rat sympathetic neurons and cardiac myocytes developing in microcultures: evidence for cholinergic, adrenergic, and dual-function neurons. Electrophysiological studies were made on microcultures (300-500 mum in diameter) in which solitary sympathetic principal neurons from newborn rats grew on previously dissociated rat heart cells. Some neurons inhibited,some excited, and others first inhibited and then excited the cardiac myocytes. Application of drugs provided evidence for secretion of acetylcholine by the first group, catecholamines by the second, and both acetylcholine and catecholamines by the third. Solitary neurons which inhibited themyocytes usually excited themselves at nicotinic synapses (autapses)."}
{"id": "PMID:186793", "title": "Relation between oxidative metabolism and slow rhythmic potentials in mammalian intestinal muscle.", "content": "Intact muscle layers separated from the small intestine of the cat were mounted in a specially designed chamber to measure electrical slow waves and NADH fluorescence simultaneously. Cooling the muscle to 17 degrees eliminated slow waves and simultaneously increased the level of fluorescence. Likewise, superfusing the muscle with a N2-bubbled glucose-free Krebs solution decreased the amplitude of slow waves and concomitantly increased fluorescence emission. In both cases, return to normal conditions reversed the effects on both slow waves and fluorescence. When signals were averaged over 30-70 slow waves, a pattern emerged with the fluorescence oscillations in phase with the electric oscillations. The NADH:NAD+ ratio reached a maximum at the most depolarized point of the slow waves and a minimum at the most polarized point between slow waves. This indicates maximum ATP utilization during the repolarization process. The correlation between redox oscillations and electrical slow wave generation is associated with cell metabolism.", "contents": "Relation between oxidative metabolism and slow rhythmic potentials in mammalian intestinal muscle. Intact muscle layers separated from the small intestine of the cat were mounted in a specially designed chamber to measure electrical slow waves and NADH fluorescence simultaneously. Cooling the muscle to 17 degrees eliminated slow waves and simultaneously increased the level of fluorescence. Likewise, superfusing the muscle with a N2-bubbled glucose-free Krebs solution decreased the amplitude of slow waves and concomitantly increased fluorescence emission. In both cases, return to normal conditions reversed the effects on both slow waves and fluorescence. When signals were averaged over 30-70 slow waves, a pattern emerged with the fluorescence oscillations in phase with the electric oscillations. The NADH:NAD+ ratio reached a maximum at the most depolarized point of the slow waves and a minimum at the most polarized point between slow waves. This indicates maximum ATP utilization during the repolarization process. The correlation between redox oscillations and electrical slow wave generation is associated with cell metabolism."}
{"id": "PMID:186817", "title": "Behavioral depression: thyroid interactions with norepinephrine-depleting drugs.", "content": "Temporary suppression of rats' bar pressing, activity, and feeding by the dopamine beta-hydroxylase inhibitor FLA-63 was synergistically potentiated by triiodothyronine (T3) treatment. The increased severity of duration of behavioral depression from the combination of mildly-depressing doses of FLA-63 (10 mg/kg, SC) and T3 (200 mug/kg, SC, 4X) was most marked 36-72 hr after FLA-63 and closely resembled the depressive syndrome produced by higher (30-90 mg/kg) doses of FLA-63 alone in timing and specific behavioral features; these depressions were more likely due to toxicity than to depletion of brain norepinephrine. T3 did not potentiate behavioral depression induced by diethyldithiocarbamate (25 mg/kg, SC). This pattern of findings suggested an interpretation of the T3-FLA-63 synergism in terms of increased FLA-63 toxicity in hyperthyroidism.", "contents": "Behavioral depression: thyroid interactions with norepinephrine-depleting drugs. Temporary suppression of rats' bar pressing, activity, and feeding by the dopamine beta-hydroxylase inhibitor FLA-63 was synergistically potentiated by triiodothyronine (T3) treatment. The increased severity of duration of behavioral depression from the combination of mildly-depressing doses of FLA-63 (10 mg/kg, SC) and T3 (200 mug/kg, SC, 4X) was most marked 36-72 hr after FLA-63 and closely resembled the depressive syndrome produced by higher (30-90 mg/kg) doses of FLA-63 alone in timing and specific behavioral features; these depressions were more likely due to toxicity than to depletion of brain norepinephrine. T3 did not potentiate behavioral depression induced by diethyldithiocarbamate (25 mg/kg, SC). This pattern of findings suggested an interpretation of the T3-FLA-63 synergism in terms of increased FLA-63 toxicity in hyperthyroidism."}
{"id": "PMID:186818", "title": "Neurohumoral correlates of sleep: further biochemical and physiological characterization of sleep perfusates.", "content": "Twenty cats were prepared surgically with electrodes for recording the EEG, Eye Movements and EMG and a push-pull cannula system in the midbrain reticular formation (MRF) allowing the extraction of perfusates during wakefulness or REM sleep. Proteins in the perfusates were analyzed by Isoelectric Focusing (IEF) polyacrylamide gels and Sodium Dodesyl Sulphate (SDS) slab gels. In addition analysis of glycoproteins was done by gas chromatography. In some cats the contribution of cerebrospinal fluid (CSF) proteins to perfusate proteins from brain tissue was studied by intraventricular injections of labelled leucine. The effect of sleep alterations on the protein cycle during sleep and wakefulness was also studied. The results of these experiments showed that most of the proteins in the perfusates are acidic, and that REM sleep perfusates contain 2 proteins M.W. 73.000 and 45.000 not present in awake perfusates, CSF or serum. It was also shown that CSF proteins do not appear to contribute to the proteins in perfusates, and that altering the sleep wake cycle, induces changes in the rhythm of protein release in perfusates. It is suggested that some relatively large polypeptides may participate in the regulation of REM sleep.", "contents": "Neurohumoral correlates of sleep: further biochemical and physiological characterization of sleep perfusates. Twenty cats were prepared surgically with electrodes for recording the EEG, Eye Movements and EMG and a push-pull cannula system in the midbrain reticular formation (MRF) allowing the extraction of perfusates during wakefulness or REM sleep. Proteins in the perfusates were analyzed by Isoelectric Focusing (IEF) polyacrylamide gels and Sodium Dodesyl Sulphate (SDS) slab gels. In addition analysis of glycoproteins was done by gas chromatography. In some cats the contribution of cerebrospinal fluid (CSF) proteins to perfusate proteins from brain tissue was studied by intraventricular injections of labelled leucine. The effect of sleep alterations on the protein cycle during sleep and wakefulness was also studied. The results of these experiments showed that most of the proteins in the perfusates are acidic, and that REM sleep perfusates contain 2 proteins M.W. 73.000 and 45.000 not present in awake perfusates, CSF or serum. It was also shown that CSF proteins do not appear to contribute to the proteins in perfusates, and that altering the sleep wake cycle, induces changes in the rhythm of protein release in perfusates. It is suggested that some relatively large polypeptides may participate in the regulation of REM sleep."}
{"id": "PMID:186819", "title": "Butanediols: selection, open field activity, and NAD reduction by liver extracts in inbred mouse strains.", "content": "Mice from the high-ethanol preferring C57BL strain and low-ethanol preferring DBA strain were tested for their preference for butanediols. The C57BL strain showed a significantly higher preference for a 10% (v/v) solution of 1,3-butanediol than the DBA strain. The C57BL strain also showed a significantly greater consumption of 1,2- and 2,3-butanediol, but the separation between strains was much smaller than with 1,3-butanediol. Both strains uniformly avoided 1,4-butanediol. Tolerance for 1,3-butanediol was tested in an open-field monitor at 3 doses. At the lowest dose the DBA strain was hyperactive and the C57BL were unaffected. At the highest dose both strains were equally depressed. The specific activity of NAD reduction on incubation of liver extracts with 1,3-butanediol and ethanol as substrates was higher with both compounds in extracts from the C57BL strain.", "contents": "Butanediols: selection, open field activity, and NAD reduction by liver extracts in inbred mouse strains. Mice from the high-ethanol preferring C57BL strain and low-ethanol preferring DBA strain were tested for their preference for butanediols. The C57BL strain showed a significantly higher preference for a 10% (v/v) solution of 1,3-butanediol than the DBA strain. The C57BL strain also showed a significantly greater consumption of 1,2- and 2,3-butanediol, but the separation between strains was much smaller than with 1,3-butanediol. Both strains uniformly avoided 1,4-butanediol. Tolerance for 1,3-butanediol was tested in an open-field monitor at 3 doses. At the lowest dose the DBA strain was hyperactive and the C57BL were unaffected. At the highest dose both strains were equally depressed. The specific activity of NAD reduction on incubation of liver extracts with 1,3-butanediol and ethanol as substrates was higher with both compounds in extracts from the C57BL strain."}
{"id": "PMID:186820", "title": "[Association of angiomas and osseous abnormalities excluding Klippel-Trenaunay disease].", "content": "The author shows that a combination of vascular diseases or anomalies with bone malformations other than the triad described by Klippel and Trenaunay or the Recklinghausen syndrome is not too rare. The author cites half-a-dozen such cases of different types, with anomalies in different parts of the body, from the cranium to the toes. The angiomas varied from naevus vinosus cavernoma, and the bone phy. In some cases the EEG shows pathological features.", "contents": "[Association of angiomas and osseous abnormalities excluding Klippel-Trenaunay disease]. The author shows that a combination of vascular diseases or anomalies with bone malformations other than the triad described by Klippel and Trenaunay or the Recklinghausen syndrome is not too rare. The author cites half-a-dozen such cases of different types, with anomalies in different parts of the body, from the cranium to the toes. The angiomas varied from naevus vinosus cavernoma, and the bone phy. In some cases the EEG shows pathological features."}
{"id": "PMID:186821", "title": "[Association of Klippel-Trenaunay and Sturge-Weber syndromes].", "content": "A woman aged 46 years, an epileptic, with no family history of hereditary disorders consulted a doctor in 1972 because of an ulcer on the right foot. She presented varices, lengthening of the right leg, and an angioma. The three components of the Klippel-Trenaunay syndrome were present. The angioma also involved the trunk, the right arm and the head where there was predilection for the trigeminal region. Radiograms of the cranium show a \"pumice-stone\" appearance of the dome and deformation of the sella turcica. The electroencephalogram showed slow waves appearing during hyperpnoea in the right temporo-rolandic region. These different elements made it possible to diagnose the Sturge-Weber syndrome. This association of the Klippel-Trenaunay and Sturge-Weber syndromes did not appear clinically to have been due to chance but appeared to be one disease akin to the phakomatoses. Thus the two syndromes that were associated can each be considered as phakomatosis.", "contents": "[Association of Klippel-Trenaunay and Sturge-Weber syndromes]. A woman aged 46 years, an epileptic, with no family history of hereditary disorders consulted a doctor in 1972 because of an ulcer on the right foot. She presented varices, lengthening of the right leg, and an angioma. The three components of the Klippel-Trenaunay syndrome were present. The angioma also involved the trunk, the right arm and the head where there was predilection for the trigeminal region. Radiograms of the cranium show a \"pumice-stone\" appearance of the dome and deformation of the sella turcica. The electroencephalogram showed slow waves appearing during hyperpnoea in the right temporo-rolandic region. These different elements made it possible to diagnose the Sturge-Weber syndrome. This association of the Klippel-Trenaunay and Sturge-Weber syndromes did not appear clinically to have been due to chance but appeared to be one disease akin to the phakomatoses. Thus the two syndromes that were associated can each be considered as phakomatosis."}
{"id": "PMID:186823", "title": "[Use of Doppler ultrasound in the examination of the extent of venous angiomas].", "content": "After emphasizing that the treatment of a strawberry naevus in a newborn is usually unnecessary, the author shows the value of the Sonar Doppler in delimiting the extent of pseudovaricose and cavernous, venous angiomas. Arterio-venous fistulas above a certain size can be localized by this procedure. Sometimes these disappear spontaneously (traumatism, thrombosis). On the other hand, the delicate arteriovenous fistulas found in cases of the Klippel and Trenaunay triad are inaccessible to this procedure.", "contents": "[Use of Doppler ultrasound in the examination of the extent of venous angiomas]. After emphasizing that the treatment of a strawberry naevus in a newborn is usually unnecessary, the author shows the value of the Sonar Doppler in delimiting the extent of pseudovaricose and cavernous, venous angiomas. Arterio-venous fistulas above a certain size can be localized by this procedure. Sometimes these disappear spontaneously (traumatism, thrombosis). On the other hand, the delicate arteriovenous fistulas found in cases of the Klippel and Trenaunay triad are inaccessible to this procedure."}
{"id": "PMID:186834", "title": "Effect of thyrotropin-releasing hormone (TRH) and antidepressant agents on brain stem and hypothalamic multiple unit activity in the cat.", "content": "The EEG and MUA (multiple unit activity) of mesencephalic reticular formation (MRF), area hypothalami posterior (PH), and area hypothalami anterior (AH) were studied in chronically implanted freely moving cats. The effects of thyrotropin-releasing hormone (TRH) and some antidepressant agents were tested on neuronal activity. Desipramine and imipramine resulted in a dose-dependent decline of MUA of all structures with the most significant decrease of activity in PH. A single injection of TRH resulted in slight or moderate gross behavioral changes and vegetative excitation lasting for 30-50 min with variable MUA levels. In the course of repetitive TRH treatment on consecutive days the gross behavioral changes and the vegetative symptoms failed to develop by the 3rd or 4th day. By that time the MUA changes of PH and MRF showed similar characteristics in response to TRH administration which was observed following the injection of desipramine and imipramine. The drugs, except for TRH, induced a suppression of paradoxical sleep cycles.", "contents": "Effect of thyrotropin-releasing hormone (TRH) and antidepressant agents on brain stem and hypothalamic multiple unit activity in the cat. The EEG and MUA (multiple unit activity) of mesencephalic reticular formation (MRF), area hypothalami posterior (PH), and area hypothalami anterior (AH) were studied in chronically implanted freely moving cats. The effects of thyrotropin-releasing hormone (TRH) and some antidepressant agents were tested on neuronal activity. Desipramine and imipramine resulted in a dose-dependent decline of MUA of all structures with the most significant decrease of activity in PH. A single injection of TRH resulted in slight or moderate gross behavioral changes and vegetative excitation lasting for 30-50 min with variable MUA levels. In the course of repetitive TRH treatment on consecutive days the gross behavioral changes and the vegetative symptoms failed to develop by the 3rd or 4th day. By that time the MUA changes of PH and MRF showed similar characteristics in response to TRH administration which was observed following the injection of desipramine and imipramine. The drugs, except for TRH, induced a suppression of paradoxical sleep cycles."}
{"id": "PMID:186835", "title": "The effect of haloperidol on epinephrine-stimulated adenylate cyclase in humans.", "content": "Administration of epinephrine in man has been shown previously to lead to a rise in plasma cyclic AMP levels by activation of the beta-adrenergic-stimulated adenylate cyclase. Therapeutic doses of lithium in humans block the epinephrine-induced rise in plasma cyclic AMP levels, suggesting that lithium inhibits beta-adrenergic adenylate cyclase. In contrast, ten subjects receiving haloperidol, a druh also effective in the treatment of mania, show a mean rise in plasma cyclic AMP levels after epinephrine administration and the magnitude of the response is the same as for non-drug treated individuals. These findings are discussed in relation to the possible pharmacological mechanisms of action of lithium and haloperidol in the control of mania.", "contents": "The effect of haloperidol on epinephrine-stimulated adenylate cyclase in humans. Administration of epinephrine in man has been shown previously to lead to a rise in plasma cyclic AMP levels by activation of the beta-adrenergic-stimulated adenylate cyclase. Therapeutic doses of lithium in humans block the epinephrine-induced rise in plasma cyclic AMP levels, suggesting that lithium inhibits beta-adrenergic adenylate cyclase. In contrast, ten subjects receiving haloperidol, a druh also effective in the treatment of mania, show a mean rise in plasma cyclic AMP levels after epinephrine administration and the magnitude of the response is the same as for non-drug treated individuals. These findings are discussed in relation to the possible pharmacological mechanisms of action of lithium and haloperidol in the control of mania."}
{"id": "PMID:186837", "title": "Routes of calcium movement across the chick chorioallantois.", "content": "The mechanism of calcium transport across the chick chorioallantois has been studied in vivo. The 15 day old membrane contains no calcium binding protein (CaBP) and attempts to stimulate transport by adding this protein or vitamin D metabolites did not enhance the normal transport process. The mitochondrial and microsomal fractions of transporting cells contain only a small percentage of the 45Ca actually moved across the epithelium and simultaneous measurements of 45Ca and 3H inulin indicate that the bulk movement of fluid is not involved in calcium transport. Calcium appears to be moved after being bound to a protein since strontium and PCMBS both interfere with transport and the membrane shows saturation kinetics. It is suggested that none of the existing theories provides an adequate explanation for the mechanism of calcium transport and some support is given to the possibility that intercellular routes are involved in part of the process.", "contents": "Routes of calcium movement across the chick chorioallantois. The mechanism of calcium transport across the chick chorioallantois has been studied in vivo. The 15 day old membrane contains no calcium binding protein (CaBP) and attempts to stimulate transport by adding this protein or vitamin D metabolites did not enhance the normal transport process. The mitochondrial and microsomal fractions of transporting cells contain only a small percentage of the 45Ca actually moved across the epithelium and simultaneous measurements of 45Ca and 3H inulin indicate that the bulk movement of fluid is not involved in calcium transport. Calcium appears to be moved after being bound to a protein since strontium and PCMBS both interfere with transport and the membrane shows saturation kinetics. It is suggested that none of the existing theories provides an adequate explanation for the mechanism of calcium transport and some support is given to the possibility that intercellular routes are involved in part of the process."}
{"id": "PMID:186838", "title": "The distribution and clearances of hormones and metabolites in the circulation of the foetal sheep.", "content": "Plasma hormone and metabolite concentrations have been measured in the plasma of blood collected simultaneously from the femoral artery, umbilical vein and carotid artery of the exteriorized foetal sheep. The concentration of vasopressin and catecholamines was consistently lower and of glucose, lactate and corticosteroids consistently higher in the umbilical vein compared with the femoral artery. ACTH concentrations showed no consistent pattern and fluctuated widely at each site, but during synacthen infusion the concentration in the umbilical vein was consistently lower than in the femoral artery. For corticosteroids the concentration in the carotid artery was much lower than that in the umbilical vein; the converse was true for catecholamines. Concentrations in the carotid and femoral artery were similar for all compounds investigated. These results indicate that the placenta is a major site of vasopressin, catecholamine and ACTH clearance and of glucose, lactate and corticosteroid production. The foetal liver is probably a major site of corticosteroid and catecholamine clearance.", "contents": "The distribution and clearances of hormones and metabolites in the circulation of the foetal sheep. Plasma hormone and metabolite concentrations have been measured in the plasma of blood collected simultaneously from the femoral artery, umbilical vein and carotid artery of the exteriorized foetal sheep. The concentration of vasopressin and catecholamines was consistently lower and of glucose, lactate and corticosteroids consistently higher in the umbilical vein compared with the femoral artery. ACTH concentrations showed no consistent pattern and fluctuated widely at each site, but during synacthen infusion the concentration in the umbilical vein was consistently lower than in the femoral artery. For corticosteroids the concentration in the carotid artery was much lower than that in the umbilical vein; the converse was true for catecholamines. Concentrations in the carotid and femoral artery were similar for all compounds investigated. These results indicate that the placenta is a major site of vasopressin, catecholamine and ACTH clearance and of glucose, lactate and corticosteroid production. The foetal liver is probably a major site of corticosteroid and catecholamine clearance."}
{"id": "PMID:186840", "title": "[Lymphography with oily contrast media. Complications and contra-indications (author's transl)].", "content": "Following lymphography pulmonary fat microembolization is regularly found. It is accompanied by hemodynamic pulmonary changes as well as by impairment of respiratory lung function and respiratory metabolism. The risks of complications and several contra-indications are described. To avoid complications explicit precautions are recommended.", "contents": "[Lymphography with oily contrast media. Complications and contra-indications (author's transl)]. Following lymphography pulmonary fat microembolization is regularly found. It is accompanied by hemodynamic pulmonary changes as well as by impairment of respiratory lung function and respiratory metabolism. The risks of complications and several contra-indications are described. To avoid complications explicit precautions are recommended."}
{"id": "PMID:186841", "title": "Clinical, radiographic and pathologic abnormalities in calcium pyrophosphate dihydrate deposition disease (CPPD): pseudogout.", "content": "Clinical, radiographic and pathologic abnormalities in calcium pyrophosphate dihydrate deposition disease (CPPD) (pseudogout) are outlined in an investigation of 85 patients with definite or probable disease and available cadaveric and human surgical material. Pyrophosphate arthropathy produced distinctive roentgenographic abnormalities with were most frequent in the knee, wrist and metacarpophalangeal joints. Although the alterations  superficially resembled osteoarthritis, they were frequently more severe and progressive with extensive fragmentation of bone, causing intra-articular osseous bodies. Pyrophosphate arthropathy occurred in unusual locations, such as the radiocarpal compartment of the wrist, elbow, and patellofemoral compartment of the knee. These characteristics allow the radiologist to suggest a probable diagnosis of CPPD even in the absence of articular calcification.", "contents": "Clinical, radiographic and pathologic abnormalities in calcium pyrophosphate dihydrate deposition disease (CPPD): pseudogout. Clinical, radiographic and pathologic abnormalities in calcium pyrophosphate dihydrate deposition disease (CPPD) (pseudogout) are outlined in an investigation of 85 patients with definite or probable disease and available cadaveric and human surgical material. Pyrophosphate arthropathy produced distinctive roentgenographic abnormalities with were most frequent in the knee, wrist and metacarpophalangeal joints. Although the alterations  superficially resembled osteoarthritis, they were frequently more severe and progressive with extensive fragmentation of bone, causing intra-articular osseous bodies. Pyrophosphate arthropathy occurred in unusual locations, such as the radiocarpal compartment of the wrist, elbow, and patellofemoral compartment of the knee. These characteristics allow the radiologist to suggest a probable diagnosis of CPPD even in the absence of articular calcification."}
{"id": "PMID:186842", "title": "Ultrasound mammography.", "content": "Ultrasound mammography was performed with unique, high resolution equipment which displays changes in acoustic properties of tissues through a calibrated gray scale. Color-coded isodensitometry was used to assist in the differential diagnosis. The rate of agreement between the ultrasound and pathological diagnoses was 86.7%. The false negative and false positive rates were 7.6% and 18.5%, respectively. Three problems must be solved before ultrasound mammography can be used as a screening device: First, additional clinical data must be accumulated. Second, the number of ultrasonograms needed for diagnosis must be reduced. Third, special equipment designed for ultrasound mammography must be developed.", "contents": "Ultrasound mammography. Ultrasound mammography was performed with unique, high resolution equipment which displays changes in acoustic properties of tissues through a calibrated gray scale. Color-coded isodensitometry was used to assist in the differential diagnosis. The rate of agreement between the ultrasound and pathological diagnoses was 86.7%. The false negative and false positive rates were 7.6% and 18.5%, respectively. Three problems must be solved before ultrasound mammography can be used as a screening device: First, additional clinical data must be accumulated. Second, the number of ultrasonograms needed for diagnosis must be reduced. Third, special equipment designed for ultrasound mammography must be developed."}
{"id": "PMID:186843", "title": "Gray-scale echography for breast cancer.", "content": "Gray-scale echography offers considerable potential as a diagnostic modality for the visualization of pathological processes in breast diseases such as carcinoma, benign cyst, fibroadenoma, mastopathy and others and is complementary to conventional techniques. Differential diagnosis of breast tumors was carried out based upon the echographic findings such as the boundary echo and shape, internal echo, and retromammary or retrotumorous shadowing. Typical echographic displays for the differential diagnosis of breast tumors from other breast lesions are presented and discussed.", "contents": "Gray-scale echography for breast cancer. Gray-scale echography offers considerable potential as a diagnostic modality for the visualization of pathological processes in breast diseases such as carcinoma, benign cyst, fibroadenoma, mastopathy and others and is complementary to conventional techniques. Differential diagnosis of breast tumors was carried out based upon the echographic findings such as the boundary echo and shape, internal echo, and retromammary or retrotumorous shadowing. Typical echographic displays for the differential diagnosis of breast tumors from other breast lesions are presented and discussed."}
{"id": "PMID:186844", "title": "Angiographic demonstration of intrahepatic arterio-portal anastomoses in hepatocellular carcinoma.", "content": "Hepatic angiograms of 114 patients with hepatocellular carcinoma (HCC) were studied, particularly changes in the portal vein branches. Arterio-portal shunts of varying sizes, evidenced by opacification of intrahepatic portal branches, were seen in 72 cases (63.2%), with retrograde opacification of the portal vein trunk in 29 (25.4%). At least four types of shunts were found: (a) through a tumor thrombus in the portal branch, (b) in a retrograde direction via a peripheral tumor nodule, (c) through a small tumor invading or amputating an artery, and (d) through a tumor located near a major portal vein branch and supplied by a large, coiling artery. Postmortem angiography of the liver in 50 patients with HCC suggests that arterio-portal shunts are the result of the special vasculature in HCC and are highly diagnostic when accompanied by other angiographic changes.", "contents": "Angiographic demonstration of intrahepatic arterio-portal anastomoses in hepatocellular carcinoma. Hepatic angiograms of 114 patients with hepatocellular carcinoma (HCC) were studied, particularly changes in the portal vein branches. Arterio-portal shunts of varying sizes, evidenced by opacification of intrahepatic portal branches, were seen in 72 cases (63.2%), with retrograde opacification of the portal vein trunk in 29 (25.4%). At least four types of shunts were found: (a) through a tumor thrombus in the portal branch, (b) in a retrograde direction via a peripheral tumor nodule, (c) through a small tumor invading or amputating an artery, and (d) through a tumor located near a major portal vein branch and supplied by a large, coiling artery. Postmortem angiography of the liver in 50 patients with HCC suggests that arterio-portal shunts are the result of the special vasculature in HCC and are highly diagnostic when accompanied by other angiographic changes."}
{"id": "PMID:186845", "title": "Non-tumorous adrenal hyperfunction: problems in angiographic-clinical correlation.", "content": "Hyperfunctioning non-neoplastic adrenal glands may be associated with Cushing's syndrome, congenital adrenal hyperplasia, and aldosteronism. The problems in radiographic diagnosis may be resolved by correlation of the angiogram with the clinical and laboratory findings.", "contents": "Non-tumorous adrenal hyperfunction: problems in angiographic-clinical correlation. Hyperfunctioning non-neoplastic adrenal glands may be associated with Cushing's syndrome, congenital adrenal hyperplasia, and aldosteronism. The problems in radiographic diagnosis may be resolved by correlation of the angiogram with the clinical and laboratory findings."}
{"id": "PMID:186846", "title": "Enzyme histochemistry as a link between biochemistry and morphology.", "content": "The presented paper describes the role of enzyme histochemistry in cell biological investigations. In the first chapter a general discussion has been given about enzyme histochemistry as a connecting link between biochemistry and morphology. The methods available for determination of enzymes in a particular cell or cell compartment have been reviewed. In this respect the characteristics of enzyme histochemistry have been discussed. Furthermore, attention has been paid to the possibilities and limitations of enzyme histochemistry. In chapter two a comparison has been made between histochemically judged and biochemically determined enzyme activities. Some fundamental differences between the biochemical and the histochemical approach in cell biological investigations are dealt with. To correlate histochemically and biochemically determined enzyme activities, a description has been given of the application of histochemical methods on isolated fractions and sucrose-ficoll gradients of these fractions. Several experimental results are described concerning the question whether a relation exists between histochemically and biochemically determined activities of respectively alkaline phosphatase, glucose-6-phosphatase, 5'-nucleotidase and 3ss-hydroxysteroid dehydrogenase. From these results the conclusion could be drawn that in general a good correlation exists between histochemically judged activity per volume (area X thickness) and biochemically determined activity per gram tissue. In chapter three the role of enzymes as markers of cellular particles and as parameters of metabolic pathways is described. Histochemical methods are available for most marker enzymes. Only activities of key enzymes can be regarded as parameters of metabolic pathways. The distribution in sucrose-ficoll gradients of enzymes, regarded as markers of mitochondria, lysosomes, endoplasmic reticulum and plasma membranes has been given. The changes occur ing under different experimental conditions for a number of marker enzymes in rat liver are described. Attention has been given to the contibution of enzyme histochemistry in the study of the heterogeneity of mitochondria, the dual localization of some (lysosomal) enzymes, the complexity of the microsomal fraction, the function of the Golgi apparatus and the heterogeneity and function of plasma membranes. Based on these results and on literature findings the possible role of some marker enzymes in cell metabolism has been discussed. In chapter four problems coherent with species and sex differences in enzyme activities are described. The interpretation of histochemical and biochemical results in view of these differences is discussed. Enzymes characteristic for a given cell type -3ss-hydroxysteroid dehydrogenase in steroid producing cells, ATP-ase in liver plasma membrane surrounding the bile canaliculi - do show less variations between species and sexes than enzymes not directly involved in specialized functions...", "contents": "Enzyme histochemistry as a link between biochemistry and morphology. The presented paper describes the role of enzyme histochemistry in cell biological investigations. In the first chapter a general discussion has been given about enzyme histochemistry as a connecting link between biochemistry and morphology. The methods available for determination of enzymes in a particular cell or cell compartment have been reviewed. In this respect the characteristics of enzyme histochemistry have been discussed. Furthermore, attention has been paid to the possibilities and limitations of enzyme histochemistry. In chapter two a comparison has been made between histochemically judged and biochemically determined enzyme activities. Some fundamental differences between the biochemical and the histochemical approach in cell biological investigations are dealt with. To correlate histochemically and biochemically determined enzyme activities, a description has been given of the application of histochemical methods on isolated fractions and sucrose-ficoll gradients of these fractions. Several experimental results are described concerning the question whether a relation exists between histochemically and biochemically determined activities of respectively alkaline phosphatase, glucose-6-phosphatase, 5'-nucleotidase and 3ss-hydroxysteroid dehydrogenase. From these results the conclusion could be drawn that in general a good correlation exists between histochemically judged activity per volume (area X thickness) and biochemically determined activity per gram tissue. In chapter three the role of enzymes as markers of cellular particles and as parameters of metabolic pathways is described. Histochemical methods are available for most marker enzymes. Only activities of key enzymes can be regarded as parameters of metabolic pathways. The distribution in sucrose-ficoll gradients of enzymes, regarded as markers of mitochondria, lysosomes, endoplasmic reticulum and plasma membranes has been given. The changes occur ing under different experimental conditions for a number of marker enzymes in rat liver are described. Attention has been given to the contibution of enzyme histochemistry in the study of the heterogeneity of mitochondria, the dual localization of some (lysosomal) enzymes, the complexity of the microsomal fraction, the function of the Golgi apparatus and the heterogeneity and function of plasma membranes. Based on these results and on literature findings the possible role of some marker enzymes in cell metabolism has been discussed. In chapter four problems coherent with species and sex differences in enzyme activities are described. The interpretation of histochemical and biochemical results in view of these differences is discussed. Enzymes characteristic for a given cell type -3ss-hydroxysteroid dehydrogenase in steroid producing cells, ATP-ase in liver plasma membrane surrounding the bile canaliculi - do show less variations between species and sexes than enzymes not directly involved in specialized functions..."}
{"id": "PMID:186847", "title": "[Involution of the mammary gland. Enzyme histochemistry, elektron microscopy and radioautography (author's transl)].", "content": "A study has been made of the progress of involution of the mouse and rat mammary gland using histologic, electron microscopic, histochemical and autoradiographic methods. Particular emphasis has been placed on the morphology, metabolic alterations and activities of histochemically identifiable enzymes, and on the pharmacologic effects of lactation inhibiting agents and cytostatic drugs on lactation and involution. In order to allow a systematic investigation, involution was initiated in rats and mice by ligation of individual gland ducts at various time intervals. Both lactating glands and glands in different phases of involution were thus available in a given animal. The most important observation was that involution, which altogether takes approximately 2 weeks to be complete, involves a three-phase process, each phase being clearly distinguishable by morphologic and histochemical criteria. The first phase comprises approximately 4 days during which production of milk may be reinitiated. The second phase starts on day 5 of involution and constitutes the period of involution per se characterized by appreciable parenchymal cell degradation. The third phase, which starts around day 10, is the period of reorganization to the resting mammary gland. Early in the first phase of involution, substantial alveolar enlargement due to engorgement with milk, together with epithelial flattening, are prominent features. By day 3, the glandular contents decrease again in volume, the number of glandular cells and the constituent cytoplasmic organelles remaining unchanged during this period, except for the diminished appearance of fat droplets. In addition to normal appearing vacuoles with only occasional or sparse protein granules, giant vacuoles containing, in part, several hundred casein granules are found. Their formation appears to be due to increased stacking of granules in distended vacuoles prior to dissociation from the Golgi apparatus. In addition, however, the enhanced reactions of alP (alkaline phosphatase) and ATPase, which are found in the apical plasmalemma, are suggestive of resorptive activities. Protein particles absorbed from the glandular lumen equally appear to have a capacity for fusing into large vacuoles. The large protein granule-containing vacuoles regularly exhibit intense beta-Glu activity. This enzyme would appear to contribute actively to the degradation of excess milk during the first phase of involution. Autoradiographic studies reveal that the synthesis and release of proteins into the secretion is maintained for 3 days. While 3H-tyrosine uptake by the alveolar cells continues unchanged, the incorporation of 3H-palmitic acid into glandular lipoids, and of 3H-fucose into glandular polysaccharides is virtually blocked completely. An immediate reaction of the lipoid metabolism is also indicated by the decrease in 3HBDH activity on the first day of involution...", "contents": "[Involution of the mammary gland. Enzyme histochemistry, elektron microscopy and radioautography (author's transl)]. A study has been made of the progress of involution of the mouse and rat mammary gland using histologic, electron microscopic, histochemical and autoradiographic methods. Particular emphasis has been placed on the morphology, metabolic alterations and activities of histochemically identifiable enzymes, and on the pharmacologic effects of lactation inhibiting agents and cytostatic drugs on lactation and involution. In order to allow a systematic investigation, involution was initiated in rats and mice by ligation of individual gland ducts at various time intervals. Both lactating glands and glands in different phases of involution were thus available in a given animal. The most important observation was that involution, which altogether takes approximately 2 weeks to be complete, involves a three-phase process, each phase being clearly distinguishable by morphologic and histochemical criteria. The first phase comprises approximately 4 days during which production of milk may be reinitiated. The second phase starts on day 5 of involution and constitutes the period of involution per se characterized by appreciable parenchymal cell degradation. The third phase, which starts around day 10, is the period of reorganization to the resting mammary gland. Early in the first phase of involution, substantial alveolar enlargement due to engorgement with milk, together with epithelial flattening, are prominent features. By day 3, the glandular contents decrease again in volume, the number of glandular cells and the constituent cytoplasmic organelles remaining unchanged during this period, except for the diminished appearance of fat droplets. In addition to normal appearing vacuoles with only occasional or sparse protein granules, giant vacuoles containing, in part, several hundred casein granules are found. Their formation appears to be due to increased stacking of granules in distended vacuoles prior to dissociation from the Golgi apparatus. In addition, however, the enhanced reactions of alP (alkaline phosphatase) and ATPase, which are found in the apical plasmalemma, are suggestive of resorptive activities. Protein particles absorbed from the glandular lumen equally appear to have a capacity for fusing into large vacuoles. The large protein granule-containing vacuoles regularly exhibit intense beta-Glu activity. This enzyme would appear to contribute actively to the degradation of excess milk during the first phase of involution. Autoradiographic studies reveal that the synthesis and release of proteins into the secretion is maintained for 3 days. While 3H-tyrosine uptake by the alveolar cells continues unchanged, the incorporation of 3H-palmitic acid into glandular lipoids, and of 3H-fucose into glandular polysaccharides is virtually blocked completely. An immediate reaction of the lipoid metabolism is also indicated by the decrease in 3HBDH activity on the first day of involution..."}
{"id": "PMID:186850", "title": "Depression of REM sleep in cats by nisoxetine, a potential antidepressant drug.", "content": "Nisoxetine, a potent and specific inhibitor of norepinephrine uptake, suppressed REM sleep in cats. Oral doses as small as 0.1 mg/kg were effective during the first 2 1/2 hours of a recording session; 0.25 mg/kg, for 5 hours. The amount of slow wave sleep increased in cats that received 0.1-1.0 mg/kg of nisoxetine. These changes in sleep pattern resemble those reported after treatment with somewhat higher doses of tricylic antidepressants.", "contents": "Depression of REM sleep in cats by nisoxetine, a potential antidepressant drug. Nisoxetine, a potent and specific inhibitor of norepinephrine uptake, suppressed REM sleep in cats. Oral doses as small as 0.1 mg/kg were effective during the first 2 1/2 hours of a recording session; 0.25 mg/kg, for 5 hours. The amount of slow wave sleep increased in cats that received 0.1-1.0 mg/kg of nisoxetine. These changes in sleep pattern resemble those reported after treatment with somewhat higher doses of tricylic antidepressants."}
{"id": "PMID:186852", "title": "Subsynaptosomal localization and biochemical characterization of serotonin binding sites in the brain.", "content": "The subsynaptosomal distribution of the borohydride stabilizable binding of serotonin (5-HT) in the brain was investigated using various enzyme markers, such as NAD glycohydrolase (NADase), Na+, K+-activated ATPase for synaptic membranes, and monoamine oxidase (MAO) for outer mitochondrial membranes. The gross distribution of the activity of NADase and Na+, K+-activated ATPase in various membrane fractions was found to parallel the distribution of 5-HT binding in these fractions. Radioactivity bound to brain fractions was extractable with chloroform-methanol (2:1). The membranous material was solubilized by chloroform-methanol (2:1) and the recovered material, suspended in 0.32 M sucrose was found to retain its 5-HT binding capacity. The protein-phospholipid nature of the binding subcellular macromolecule was demonstrated with proteolytic and lipolytic enzymes.", "contents": "Subsynaptosomal localization and biochemical characterization of serotonin binding sites in the brain. The subsynaptosomal distribution of the borohydride stabilizable binding of serotonin (5-HT) in the brain was investigated using various enzyme markers, such as NAD glycohydrolase (NADase), Na+, K+-activated ATPase for synaptic membranes, and monoamine oxidase (MAO) for outer mitochondrial membranes. The gross distribution of the activity of NADase and Na+, K+-activated ATPase in various membrane fractions was found to parallel the distribution of 5-HT binding in these fractions. Radioactivity bound to brain fractions was extractable with chloroform-methanol (2:1). The membranous material was solubilized by chloroform-methanol (2:1) and the recovered material, suspended in 0.32 M sucrose was found to retain its 5-HT binding capacity. The protein-phospholipid nature of the binding subcellular macromolecule was demonstrated with proteolytic and lipolytic enzymes."}
{"id": "PMID:186853", "title": "Effects of methysergide in cats deprived of paradoxical sleep.", "content": "Methysergide maleate, a 5-hydroxytryptamine receptor blocker, was administered to cats deprived of paradoxical sleep for 48 hours. During the first six hours after methysergide, the latency to the first slow-wave sleep and paradoxical sleep episodes was increased and total sleep time decreased. The decrease in sleep reflects a loss of paradoxical sleep, while the amount of slow-wave sleep remained unchanged. Slow-wave sleep time, though unchanged in amount, was displaced to the end of the six-hour recording period. These results suggest that paradoxical sleep in cats is more sensitive to methysergide action than is slow-wave sleep.", "contents": "Effects of methysergide in cats deprived of paradoxical sleep. Methysergide maleate, a 5-hydroxytryptamine receptor blocker, was administered to cats deprived of paradoxical sleep for 48 hours. During the first six hours after methysergide, the latency to the first slow-wave sleep and paradoxical sleep episodes was increased and total sleep time decreased. The decrease in sleep reflects a loss of paradoxical sleep, while the amount of slow-wave sleep remained unchanged. Slow-wave sleep time, though unchanged in amount, was displaced to the end of the six-hour recording period. These results suggest that paradoxical sleep in cats is more sensitive to methysergide action than is slow-wave sleep."}
{"id": "PMID:186855", "title": "[Granular cell pituicytoma (choristoma) of the pituitary stalk].", "content": "A case of granular cell tumour in the pituitary stalk is described marked by the sudden loss of visual acuity in the left eye, followed by the right years later. A comparison with 17 cases previously published and with cases of asymptomatic granular cell nodules leads the authors to suggest the term granular cell pituicytoma. They discuss the place of this neoformation among other systemic granular cell tumours (granular cell myoblastoma). Fifteen patients were operated on, complete excision being carried out in only three (including the case published). Whether complementary cobalt therapy is useful remains problematical since very few cases have been published because of the slow development of the neoplasm.", "contents": "[Granular cell pituicytoma (choristoma) of the pituitary stalk]. A case of granular cell tumour in the pituitary stalk is described marked by the sudden loss of visual acuity in the left eye, followed by the right years later. A comparison with 17 cases previously published and with cases of asymptomatic granular cell nodules leads the authors to suggest the term granular cell pituicytoma. They discuss the place of this neoformation among other systemic granular cell tumours (granular cell myoblastoma). Fifteen patients were operated on, complete excision being carried out in only three (including the case published). Whether complementary cobalt therapy is useful remains problematical since very few cases have been published because of the slow development of the neoplasm."}
{"id": "PMID:186858", "title": "Motilin and motilin analogues: mode of action.", "content": "Natural porcine motilin (13-methionine-motilin) and its synthetic position 13-substituted analogues, 13-norleucine-motilin and 13-leucine-motilin, are of equal efficacy for gastrointestinal motor activity. Pharmacological in vitro analysis reveals that motilin effects on the gastrointestinal muscle are not mediated via nervous pathways but are brought about by direct action of the polypeptide on the muscle cell. As the contractile response to motilin can be abolished by the Ca++ antagonistic compound verapamil, a role for motilin in the transport of Ca++ to the cytosol of intestinal smooth muscle might be considered. Ca++ fluxes seem to be linked to intracellular cyclic guanosine-3':5'-monophosphate and the antagonistic cyclic adenosine-3':5'-monophosphate. By contrast, in motilin-stimulated gastric pepsin secretion, there is no evidence for a mediating role of cyclic nucleotides. It is more likely that the pepsigogic effect is brought about by augmented gastric mucosal blood flow.", "contents": "Motilin and motilin analogues: mode of action. Natural porcine motilin (13-methionine-motilin) and its synthetic position 13-substituted analogues, 13-norleucine-motilin and 13-leucine-motilin, are of equal efficacy for gastrointestinal motor activity. Pharmacological in vitro analysis reveals that motilin effects on the gastrointestinal muscle are not mediated via nervous pathways but are brought about by direct action of the polypeptide on the muscle cell. As the contractile response to motilin can be abolished by the Ca++ antagonistic compound verapamil, a role for motilin in the transport of Ca++ to the cytosol of intestinal smooth muscle might be considered. Ca++ fluxes seem to be linked to intracellular cyclic guanosine-3':5'-monophosphate and the antagonistic cyclic adenosine-3':5'-monophosphate. By contrast, in motilin-stimulated gastric pepsin secretion, there is no evidence for a mediating role of cyclic nucleotides. It is more likely that the pepsigogic effect is brought about by augmented gastric mucosal blood flow."}
{"id": "PMID:186859", "title": "Effect of salbutamol inhalations of plasma and urinary cyclic adenosine monophosphate levels in asthmatics and non-atopic controls.", "content": "Twenty asthmatics and 14 non-atopic controls were given long-acting theophylline tablets, 400 mg twice daily, and were then challenged, after a control period, with 0.5 mg salbutamol as an inhalant, divided in two doses. Urinary and plasma cyclic adenosine monophosphate (cAMP) levels were determined at the beginning of the study, during theophylline treatment and after the challenge with salbutamol inhalation. In neither the asthmatics nor the controls did theophylline alone raise the concentration of cAMP in plasma or its excretion in urine. Inhalation of salbutamol caused a significant rise in plasma cAMP levels in the controls but not in asthmatics. The inhaled sympathomimetic aerosol caused a slight simultaneous rise in urinary cAMP excretion in non-atopic controls, but in the asthmatics. Our results show that sympathomimetics administered directly to the bronchial mucosa do not elicit the same metabolic cAMP response in asthmatics as in controls.", "contents": "Effect of salbutamol inhalations of plasma and urinary cyclic adenosine monophosphate levels in asthmatics and non-atopic controls. Twenty asthmatics and 14 non-atopic controls were given long-acting theophylline tablets, 400 mg twice daily, and were then challenged, after a control period, with 0.5 mg salbutamol as an inhalant, divided in two doses. Urinary and plasma cyclic adenosine monophosphate (cAMP) levels were determined at the beginning of the study, during theophylline treatment and after the challenge with salbutamol inhalation. In neither the asthmatics nor the controls did theophylline alone raise the concentration of cAMP in plasma or its excretion in urine. Inhalation of salbutamol caused a significant rise in plasma cAMP levels in the controls but not in asthmatics. The inhaled sympathomimetic aerosol caused a slight simultaneous rise in urinary cAMP excretion in non-atopic controls, but in the asthmatics. Our results show that sympathomimetics administered directly to the bronchial mucosa do not elicit the same metabolic cAMP response in asthmatics as in controls."}
{"id": "PMID:186860", "title": "Flexible fiberopitc bronchoscopy in the diagnosis of bronchial carcinoma.", "content": "Forty-eight patients with primary bronchial carcinomas have been examined, and 41 of these carcinomas (85%) were confirmed by histopathological or cytological tests on samples taken during flexible fiberoptic bronchoscopy. Thirty-seven patients (77%) were diagnosed histopathologically, based on forceps biopsy, and four cases cytologically, based on investigations of bronchial secretions and brush biopsies. In nine of 14 patients with peripheral tumours the diagnosis was verified by flexible fiberoptic bronchoscopy. We find this a very safe and useful method in the early diagnosis of bronchial carcinoma.", "contents": "Flexible fiberopitc bronchoscopy in the diagnosis of bronchial carcinoma. Forty-eight patients with primary bronchial carcinomas have been examined, and 41 of these carcinomas (85%) were confirmed by histopathological or cytological tests on samples taken during flexible fiberoptic bronchoscopy. Thirty-seven patients (77%) were diagnosed histopathologically, based on forceps biopsy, and four cases cytologically, based on investigations of bronchial secretions and brush biopsies. In nine of 14 patients with peripheral tumours the diagnosis was verified by flexible fiberoptic bronchoscopy. We find this a very safe and useful method in the early diagnosis of bronchial carcinoma."}
{"id": "PMID:186857", "title": "Diffusible cholesterol as a risk factor in the biochemical stage of atherosclerosis.", "content": "The variations of diffusible cholesterol, considered as one of the risk factors involved in the biochemical processes of the subclinical, premorphologic stage of atherosclerosis, were studied in patients with cardiovascular disturbances. To this end, total cholesterol, diffusible cholesterol and beta-lipoproteins were assayed in the blood of 76 such patients and in their children. A correlation was observed between the increase of diffusible cholesterol values and those of beta-lipoproteins. In some of these cases, high diffusible cholesterol values showed a hereditary character.", "contents": "Diffusible cholesterol as a risk factor in the biochemical stage of atherosclerosis. The variations of diffusible cholesterol, considered as one of the risk factors involved in the biochemical processes of the subclinical, premorphologic stage of atherosclerosis, were studied in patients with cardiovascular disturbances. To this end, total cholesterol, diffusible cholesterol and beta-lipoproteins were assayed in the blood of 76 such patients and in their children. A correlation was observed between the increase of diffusible cholesterol values and those of beta-lipoproteins. In some of these cases, high diffusible cholesterol values showed a hereditary character."}
{"id": "PMID:186863", "title": "[Radiological studies in otology].", "content": "Skull X-rays with special projections, particularly tomography of the temporal bone, are very helpful procedures in the differential diagnosis of diseases of the temporal bone. Tomography serves to delineate the size and distribution of tumors in the middle or inner ear. Furthermore, in fractures of the temporal bone the fracture line can be seen throughout the entire osseous structure. Special projections are reported for tomography of the temporal bone, with special emphasis on the indications for such procedures. Meatocisternography, a study in which the internal auditory canal is filled with contrast medium, shows defects caused by neurinomas. Indications for angiography (carotid or vertebral) are large neurinomas penetrating the posterior fossa or other tumors of the inner or middle ear, i.e. chemodectomas. A chemodectoma of the jugular bulb can also be demonstrated by jugular venography.", "contents": "[Radiological studies in otology]. Skull X-rays with special projections, particularly tomography of the temporal bone, are very helpful procedures in the differential diagnosis of diseases of the temporal bone. Tomography serves to delineate the size and distribution of tumors in the middle or inner ear. Furthermore, in fractures of the temporal bone the fracture line can be seen throughout the entire osseous structure. Special projections are reported for tomography of the temporal bone, with special emphasis on the indications for such procedures. Meatocisternography, a study in which the internal auditory canal is filled with contrast medium, shows defects caused by neurinomas. Indications for angiography (carotid or vertebral) are large neurinomas penetrating the posterior fossa or other tumors of the inner or middle ear, i.e. chemodectomas. A chemodectoma of the jugular bulb can also be demonstrated by jugular venography."}
{"id": "PMID:186864", "title": "[Hyperlipemia: practical attitudes].", "content": "Serum cholesterol and triglyceride levels may vary widely in a given patient, and therefore both of these lipid determinations should be repeated for initial evaluation. Later, the response of lipid values to diet and to drugs provides more information on the individual characteristics of a hyperlipoproteinemia than \"typing\" from one lipid evaluation. The type may actually change with lipid levels, whereas the basic tendencies to increased betalipoproteins (evaluated as cholesteremia) or prebetalipoproteins (evaluated as triglycerides) are more constant features in a patient. Alimentary conditions in most cases influence hyperlipemias, whether primary or secondary. Total caloric intake is a major factor in inducing augmented triglycerides in predisposed people. Hypertriglyceridemia is rare before 20 and not frequent in women. On the other hand, familial hypercholesteremia is present from the first weeks of life. Diet is of little help in these cases. When hypercholesteremia is related to food habits it usually appears after the third decade. The amount of fats rich in saturated fatty acids appears to be the chief causative factor in this regard. However, it is possible that genetic factors also affect the degree of alimentary influence on cholesterol level over many years. The use of hypolipemic drugs does not obviate the need for appropriate diet. If the prevention of early coronary disease is to be successful it should start in young people before the first clinical symptoms appear.", "contents": "[Hyperlipemia: practical attitudes]. Serum cholesterol and triglyceride levels may vary widely in a given patient, and therefore both of these lipid determinations should be repeated for initial evaluation. Later, the response of lipid values to diet and to drugs provides more information on the individual characteristics of a hyperlipoproteinemia than \"typing\" from one lipid evaluation. The type may actually change with lipid levels, whereas the basic tendencies to increased betalipoproteins (evaluated as cholesteremia) or prebetalipoproteins (evaluated as triglycerides) are more constant features in a patient. Alimentary conditions in most cases influence hyperlipemias, whether primary or secondary. Total caloric intake is a major factor in inducing augmented triglycerides in predisposed people. Hypertriglyceridemia is rare before 20 and not frequent in women. On the other hand, familial hypercholesteremia is present from the first weeks of life. Diet is of little help in these cases. When hypercholesteremia is related to food habits it usually appears after the third decade. The amount of fats rich in saturated fatty acids appears to be the chief causative factor in this regard. However, it is possible that genetic factors also affect the degree of alimentary influence on cholesterol level over many years. The use of hypolipemic drugs does not obviate the need for appropriate diet. If the prevention of early coronary disease is to be successful it should start in young people before the first clinical symptoms appear."}
{"id": "PMID:186865", "title": "[Hyperlipemia and diabetes].", "content": "There are several causes for hyperlipemia in the diabetic: (a) an increase in hepatic synthesis of prebetalipoproteins, and (b) reduced elimination of prebetalipoproteins and chylomicrons from the bloodstream, due to diminished activity of lipoprotein lipase in insulin deficiency. The role of heredity has been put in doubt by the observation that diabetes and hypertriglyceridemia are not transmitted by the same genetic factor. The shortterm and longterm implications of diabetic hyperlipemia are discussed, together with the treatment.", "contents": "[Hyperlipemia and diabetes]. There are several causes for hyperlipemia in the diabetic: (a) an increase in hepatic synthesis of prebetalipoproteins, and (b) reduced elimination of prebetalipoproteins and chylomicrons from the bloodstream, due to diminished activity of lipoprotein lipase in insulin deficiency. The role of heredity has been put in doubt by the observation that diabetes and hypertriglyceridemia are not transmitted by the same genetic factor. The shortterm and longterm implications of diabetic hyperlipemia are discussed, together with the treatment."}
{"id": "PMID:186866", "title": "[Ambulatory diagnostic methods in disorders of sex maturation].", "content": "The most important investigative methods for study of disorders of pubertal development are simple. However, they require a detailed knowledge of the normal course of puberty. In most cases the family history (height of the parents, course of puberty in the father, age at menarche of the mother), personal history (growth curve, height velocity) and physical examination (height measurement, evaluation of stage of pubertal development, bone age) make it possible to decied whether there is benign delayed growth and development (a variation of normal) or whether the patient is suffering from one of the rare types of true hypogonadism (hormonal disorder or types of true hypogonadism (hormonal disorder or chromosomal anomaly). Only when there is strong suspicion of hypogonadism should the expensive and complicated laboratory and chromosome studies be carried out. They serve to detect a disorder of the end organ or of the hypothalamus-pituitary system (determination of testosterone or estradiol, determination of LH and FSH before and after stimulation with the releasing hormone LHRH, determination of growth hormone before and after insulin and arginine, determination of TSH before and after TRH). Although endocrine disorders are rarely the cause of delayed puberty, their diagnosis is important with a view to causal treatment.", "contents": "[Ambulatory diagnostic methods in disorders of sex maturation]. The most important investigative methods for study of disorders of pubertal development are simple. However, they require a detailed knowledge of the normal course of puberty. In most cases the family history (height of the parents, course of puberty in the father, age at menarche of the mother), personal history (growth curve, height velocity) and physical examination (height measurement, evaluation of stage of pubertal development, bone age) make it possible to decied whether there is benign delayed growth and development (a variation of normal) or whether the patient is suffering from one of the rare types of true hypogonadism (hormonal disorder or types of true hypogonadism (hormonal disorder or chromosomal anomaly). Only when there is strong suspicion of hypogonadism should the expensive and complicated laboratory and chromosome studies be carried out. They serve to detect a disorder of the end organ or of the hypothalamus-pituitary system (determination of testosterone or estradiol, determination of LH and FSH before and after stimulation with the releasing hormone LHRH, determination of growth hormone before and after insulin and arginine, determination of TSH before and after TRH). Although endocrine disorders are rarely the cause of delayed puberty, their diagnosis is important with a view to causal treatment."}
{"id": "PMID:186867", "title": "[Recent developments in the etiology and diagnosis of Basedow's disease].", "content": "The etiology and diagnosis of Grave's disease are briefly reviewed with particular reference to newer discoveries in the wide range of immunoglobulins which might act as humoral stimulators of the thyroid. Diagnosis of hyperthyroidism has been greatly facilitated by radioimmunologic determination of serum T4 and T3 and indirect estimation of T4 (T4 index). In this way 85-90% of cases can be diagnosed with a single blood sample. TRH tests and T3 suppression tests are only rarely required.", "contents": "[Recent developments in the etiology and diagnosis of Basedow's disease]. The etiology and diagnosis of Grave's disease are briefly reviewed with particular reference to newer discoveries in the wide range of immunoglobulins which might act as humoral stimulators of the thyroid. Diagnosis of hyperthyroidism has been greatly facilitated by radioimmunologic determination of serum T4 and T3 and indirect estimation of T4 (T4 index). In this way 85-90% of cases can be diagnosed with a single blood sample. TRH tests and T3 suppression tests are only rarely required."}
{"id": "PMID:186868", "title": "Vertebrate central nervous system: same neurons mediate both electrical and chemical inhibitions.", "content": "Identified goldfish medullary interneurons previously shown to inhibit the Mauthner cell electrically also produce a classical postsynaptic inhibition of that cell. Failure of active spike propagation in the processes of these interneurons underlies generation of the electrical component, and the resultant electrotonic terminal depolarization is sufficient to evoke inhibitory transmitter release.", "contents": "Vertebrate central nervous system: same neurons mediate both electrical and chemical inhibitions. Identified goldfish medullary interneurons previously shown to inhibit the Mauthner cell electrically also produce a classical postsynaptic inhibition of that cell. Failure of active spike propagation in the processes of these interneurons underlies generation of the electrical component, and the resultant electrotonic terminal depolarization is sufficient to evoke inhibitory transmitter release."}
{"id": "PMID:186869", "title": "The renin-angiotensin system and thirst: a reevaluation.", "content": "Systemic injections of renin that stimulate substantial amounts of drinking in nephrectomized rats can produce plasma renin activities that fall well above the physiological range. Furthermore, increases in plasma renin activities that occur in rats with intact kidneys during experimental hypotension appear to be too low to provide the basis for the observed elevations in water intake. These findings question the contribution of the renin-angiotensin system to thirst under normal physiological conditions.", "contents": "The renin-angiotensin system and thirst: a reevaluation. Systemic injections of renin that stimulate substantial amounts of drinking in nephrectomized rats can produce plasma renin activities that fall well above the physiological range. Furthermore, increases in plasma renin activities that occur in rats with intact kidneys during experimental hypotension appear to be too low to provide the basis for the observed elevations in water intake. These findings question the contribution of the renin-angiotensin system to thirst under normal physiological conditions."}
{"id": "PMID:186870", "title": "Synaptic facilitation and behavioral sensitization in Aplysia: possible role of serotonin and cyclic  AMP.", "content": "The neural changes accompanying sensitization of the gill-withdrawal reflex in Aplysia are associated with presynaptic facilitation at monosynaptic connections between sensory neurons and motor cells. To analyze the molecular mechanisms underlying the facilitation, the pharmacological actions of serotonin, octopamine, and dopamine were examined. Only serotonin enhanced synaptic transmission between the sensory and the motor neurons. A serotonin antagonist, cinanserin, reversibly blocked the synaptic facilitation. The action of serotonin may be mediated by adenosime 3',5'-monophosphate (cyclic AMP). Exposing the ganglion to dibutyryl cyclic AMP or injecting cyclic AMP into the cell body enhances the synaptic action of a sensory neuron. The mechanism of presynaptic facilitation, therefore, may include activation of one or more serotonergic neurons, which enhance the release of a neurotransmitter by increasing the intracellular concentration of cyclic AMP in the terminals of the sensory neurons.", "contents": "Synaptic facilitation and behavioral sensitization in Aplysia: possible role of serotonin and cyclic  AMP. The neural changes accompanying sensitization of the gill-withdrawal reflex in Aplysia are associated with presynaptic facilitation at monosynaptic connections between sensory neurons and motor cells. To analyze the molecular mechanisms underlying the facilitation, the pharmacological actions of serotonin, octopamine, and dopamine were examined. Only serotonin enhanced synaptic transmission between the sensory and the motor neurons. A serotonin antagonist, cinanserin, reversibly blocked the synaptic facilitation. The action of serotonin may be mediated by adenosime 3',5'-monophosphate (cyclic AMP). Exposing the ganglion to dibutyryl cyclic AMP or injecting cyclic AMP into the cell body enhances the synaptic action of a sensory neuron. The mechanism of presynaptic facilitation, therefore, may include activation of one or more serotonergic neurons, which enhance the release of a neurotransmitter by increasing the intracellular concentration of cyclic AMP in the terminals of the sensory neurons."}
{"id": "PMID:186871", "title": "[Septicemia due to Torulopsis glabrata].", "content": "The authors report a case of fungal septicemia due to Torulopsis glabrata, an unusual cause of fungus infections. This case was of interest clinically in view of the duration and tenacity of the infection on a surgical unit, where repeated blood cultures were positive for Torulopsis glabrata and the fungus was isolated from other samples during the same period. In the laboratory, the species identified was a common saprophyte of the mucosae and natural cavities of man; it seems to be only rarely pathogenic. Finally the course marked by numerous relapses was later favourable thanks to the use of antifungal agents chosen in the light of laboratory examinations.", "contents": "[Septicemia due to Torulopsis glabrata]. The authors report a case of fungal septicemia due to Torulopsis glabrata, an unusual cause of fungus infections. This case was of interest clinically in view of the duration and tenacity of the infection on a surgical unit, where repeated blood cultures were positive for Torulopsis glabrata and the fungus was isolated from other samples during the same period. In the laboratory, the species identified was a common saprophyte of the mucosae and natural cavities of man; it seems to be only rarely pathogenic. Finally the course marked by numerous relapses was later favourable thanks to the use of antifungal agents chosen in the light of laboratory examinations."}
{"id": "PMID:186872", "title": "[Hodgkin's disease and pregnancy].", "content": "The onset of pregnancy raises special problems during Hodgkin's disease and renders difficult full assessment of the extent of the disease. Furthermore acute exacerbations are fairly common, except in patients with a complete remission for more than two years. The critical period seems to be labour and the following weeks. In fact when pregnancy occurs during Hodgkin's disease, one may decide to interrupt it. However, if the patient has been in remission for more than two years, one may allow the pregnancy to continue. The decision will be taken in the light of each case. After pregnancy contraception should be advised in all women with Hodgkin's disease.", "contents": "[Hodgkin's disease and pregnancy]. The onset of pregnancy raises special problems during Hodgkin's disease and renders difficult full assessment of the extent of the disease. Furthermore acute exacerbations are fairly common, except in patients with a complete remission for more than two years. The critical period seems to be labour and the following weeks. In fact when pregnancy occurs during Hodgkin's disease, one may decide to interrupt it. However, if the patient has been in remission for more than two years, one may allow the pregnancy to continue. The decision will be taken in the light of each case. After pregnancy contraception should be advised in all women with Hodgkin's disease."}
{"id": "PMID:186873", "title": "[Femoral nerve paralysis complicating anticoagulant treatments. A propos of 3 cases].", "content": "The authors report 3 new cases of femoral nerve paralysis complicating anticoagulant treatment. The first sign was pain, the neurological signs occurred later and the patient usually recovered but recovery was sometimes incomplete. The pathogenesis is not clear : a muscle hematoma, ischemia of the nerve trunk, and intraneural hemorrhage are the commonest theories.", "contents": "[Femoral nerve paralysis complicating anticoagulant treatments. A propos of 3 cases]. The authors report 3 new cases of femoral nerve paralysis complicating anticoagulant treatment. The first sign was pain, the neurological signs occurred later and the patient usually recovered but recovery was sometimes incomplete. The pathogenesis is not clear : a muscle hematoma, ischemia of the nerve trunk, and intraneural hemorrhage are the commonest theories."}
{"id": "PMID:186878", "title": "[Digestive lesions after abdominopelvic irradiation, in the treatment of cancers of the genital tract].", "content": "The authors report 15 cases collected over a few years on a gastroenterology unit, and emphasize the digestive complications occurring after pelvic or abdomino-pelvic irradiation for genital carcinoma. The rectum and pelvic colon are generally affected. The delays of onset after radiotherapy may reach or exceed several months. The vascular lesions, caused by ionising radiation, explain the tissue ischemia and, consequently the failure of local medical treatment. When severe hemorrhage or visceral perforation occur, surgery is necessary. However, sutures often break down on these insufficiently vascularised tissues and re-operation is always associated with a poor prognosis.", "contents": "[Digestive lesions after abdominopelvic irradiation, in the treatment of cancers of the genital tract]. The authors report 15 cases collected over a few years on a gastroenterology unit, and emphasize the digestive complications occurring after pelvic or abdomino-pelvic irradiation for genital carcinoma. The rectum and pelvic colon are generally affected. The delays of onset after radiotherapy may reach or exceed several months. The vascular lesions, caused by ionising radiation, explain the tissue ischemia and, consequently the failure of local medical treatment. When severe hemorrhage or visceral perforation occur, surgery is necessary. However, sutures often break down on these insufficiently vascularised tissues and re-operation is always associated with a poor prognosis."}
{"id": "PMID:186879", "title": "[Non-parasitic cysts of the spleen. 2 cases].", "content": "Although splenic cysts are benign, a gradual increase in volume of the liquid mass often leads to diagnosis owing to the large volume. The two cases reported are an example of this. A cure was obtained by splenectomy. It is usually easy to carry out and the prognosis is benign.", "contents": "[Non-parasitic cysts of the spleen. 2 cases]. Although splenic cysts are benign, a gradual increase in volume of the liquid mass often leads to diagnosis owing to the large volume. The two cases reported are an example of this. A cure was obtained by splenectomy. It is usually easy to carry out and the prognosis is benign."}
{"id": "PMID:186880", "title": "[Practical value of gastric intubation during peptic ulcer. Analysis of 410 cases, after Histalog stimulation].", "content": "This study was carried out in 410 subjects, collecting gastric fluid for one hour, after 15 minutes emptying and one hour, after 15 minutes emptying and one hour's study of basal secretion using, as stimulant, Histalog at a maximal dose of 2 mg/kg without exceeding 130 mg. The object of this statistical analysis was to determine the average figures and the standard deviations of the volumes of secretions, together with those of the output of hydrogen ions in 5 groups of subjects: controls (60), gastric ulcers (38), duodenal ulcers (200), patients suspected of duodenal ulcer (60) or affected by dyspeptic syndrome without radiological nor endoscopic lesions (52). In the normal subject, the hydrochloric acid output was situated between 5 and 27 mEq. The diagnosis of duodenal ulcer was very unlikely when secretion was less than 9 mEq in man and almost certain above 30 mEq.", "contents": "[Practical value of gastric intubation during peptic ulcer. Analysis of 410 cases, after Histalog stimulation]. This study was carried out in 410 subjects, collecting gastric fluid for one hour, after 15 minutes emptying and one hour, after 15 minutes emptying and one hour's study of basal secretion using, as stimulant, Histalog at a maximal dose of 2 mg/kg without exceeding 130 mg. The object of this statistical analysis was to determine the average figures and the standard deviations of the volumes of secretions, together with those of the output of hydrogen ions in 5 groups of subjects: controls (60), gastric ulcers (38), duodenal ulcers (200), patients suspected of duodenal ulcer (60) or affected by dyspeptic syndrome without radiological nor endoscopic lesions (52). In the normal subject, the hydrochloric acid output was situated between 5 and 27 mEq. The diagnosis of duodenal ulcer was very unlikely when secretion was less than 9 mEq in man and almost certain above 30 mEq."}
{"id": "PMID:186881", "title": "[New data on the disease induced by laxatives].", "content": "The authors report 5 personal case and recall the physiopathological mechanisms of metabolic disorders observed during the abuse of laxatives. They emphasize the fact that electrolyte losses were not only fecal, but also aggravated by frequent use of diuretics or dietary restriction. One may oppose the constant, very marked fall in body potassium to the variation in sodium content of the organism. Oedema formed part of the clinical picture. The withdrawal of drastic laxatives and diuretics, led to rapid recovery of all the symptoms.", "contents": "[New data on the disease induced by laxatives]. The authors report 5 personal case and recall the physiopathological mechanisms of metabolic disorders observed during the abuse of laxatives. They emphasize the fact that electrolyte losses were not only fecal, but also aggravated by frequent use of diuretics or dietary restriction. One may oppose the constant, very marked fall in body potassium to the variation in sodium content of the organism. Oedema formed part of the clinical picture. The withdrawal of drastic laxatives and diuretics, led to rapid recovery of all the symptoms."}
{"id": "PMID:186882", "title": "[Caustic burn and adenocarcinoma of the esophagus].", "content": "Adenocarcinoma of the esophagus is found almost exclusively at the level of the cardia. It is exceptional to find it in the middle part of the esophagus in the absence of involvement of the cardia. In the long term, caustic burns of the esophagus may favour malignant degeneration. The latter is always squamous cell carcinoma. In our patient, a 28 year old man, a cylindrical carcinoma of the thoracic esophagus was detected four years after the ingestion of concentrated sodium hypochlorite. The caustic burn followed by carcinoma were of special significance in this case owing to the development of an adenocarcinoma.", "contents": "[Caustic burn and adenocarcinoma of the esophagus]. Adenocarcinoma of the esophagus is found almost exclusively at the level of the cardia. It is exceptional to find it in the middle part of the esophagus in the absence of involvement of the cardia. In the long term, caustic burns of the esophagus may favour malignant degeneration. The latter is always squamous cell carcinoma. In our patient, a 28 year old man, a cylindrical carcinoma of the thoracic esophagus was detected four years after the ingestion of concentrated sodium hypochlorite. The caustic burn followed by carcinoma were of special significance in this case owing to the development of an adenocarcinoma."}
{"id": "PMID:186887", "title": "[Sacrocoxitis due to common bacteria].", "content": "The authors report 11 cases of sacro-coxitis due to pyogenic bacteria observed over a period of seven years and emphasize that this is a disease of young women recently in labour, usually due to staphylococci which enter through the genital tract. The other methods of contamination are urinary, cutaneous and dental. The onset is usually acute, pseudoembolic and bacteremia. Whereas the diagnosis is purely clinical as X ray remains normal until the 15th or 20th day, all steps should be taken to identify the germ. With antibiotics, a cure is obtained without sequelae within 3 months. Surgery is only justified if tuberculosis is suspected and in exceptional cases with abscess formation.", "contents": "[Sacrocoxitis due to common bacteria]. The authors report 11 cases of sacro-coxitis due to pyogenic bacteria observed over a period of seven years and emphasize that this is a disease of young women recently in labour, usually due to staphylococci which enter through the genital tract. The other methods of contamination are urinary, cutaneous and dental. The onset is usually acute, pseudoembolic and bacteremia. Whereas the diagnosis is purely clinical as X ray remains normal until the 15th or 20th day, all steps should be taken to identify the germ. With antibiotics, a cure is obtained without sequelae within 3 months. Surgery is only justified if tuberculosis is suspected and in exceptional cases with abscess formation."}
{"id": "PMID:186888", "title": "[Colitis marginal to cancer. Apropos of 7 cases].", "content": "The authors report 7 new cases of colitis above a carcinoma. The study of these cases and of those reported in the literature shows the main pathological characteristics of the lesions and permits discussion of the pathogenesis. Chronic ischemia caused by an increase in intraluminal pressure above the neoplastic stenosis seems to be the main etiological factor.", "contents": "[Colitis marginal to cancer. Apropos of 7 cases]. The authors report 7 new cases of colitis above a carcinoma. The study of these cases and of those reported in the literature shows the main pathological characteristics of the lesions and permits discussion of the pathogenesis. Chronic ischemia caused by an increase in intraluminal pressure above the neoplastic stenosis seems to be the main etiological factor."}
{"id": "PMID:186896", "title": "[Intestinal lesions induced by radiotherapy of malignant pelvic tumors. Apropos of 2 cases].", "content": "Intestinal lesions after radiotherapy for pelvic malignant tumours are of two types: ulcerative colitis with stenosis and hemorrhage sometimes sevre and repeated, and ileal involvement with focal ischemic lesions and malabsorption responsible for nutritional disorders. It is difficult to distinguish them from a recurrence of the tumour in spite of endoscopy, arteriography and biopsy. The course in 3 stages is of great value in diagnosis. A reduction in the frequency of such complications may be hoped for by assessment and exclusion of predisposing factors, by strict observance of therapeutic rules. They are serious owing to the marked irreversible conjunctivo-vascular changes and the fragility of the irradiated tissues during operation.", "contents": "[Intestinal lesions induced by radiotherapy of malignant pelvic tumors. Apropos of 2 cases]. Intestinal lesions after radiotherapy for pelvic malignant tumours are of two types: ulcerative colitis with stenosis and hemorrhage sometimes sevre and repeated, and ileal involvement with focal ischemic lesions and malabsorption responsible for nutritional disorders. It is difficult to distinguish them from a recurrence of the tumour in spite of endoscopy, arteriography and biopsy. The course in 3 stages is of great value in diagnosis. A reduction in the frequency of such complications may be hoped for by assessment and exclusion of predisposing factors, by strict observance of therapeutic rules. They are serious owing to the marked irreversible conjunctivo-vascular changes and the fragility of the irradiated tissues during operation."}
{"id": "PMID:186897", "title": "[Value of identification of renal pedicles in the echotomographic study of the normal and pathological pancreas].", "content": "The renal pedicles were identified in 83.5% of pancreases during echotomography. The horizontal relations together with the vertical relations represented by the abdominal aorta and inferior vena cava permit one to localise with precision the cephalic and corporeal parts of the pancreas for they are situated just in front. Analysis of the echostructure of the pancreas thus localised is greatly facilitated.", "contents": "[Value of identification of renal pedicles in the echotomographic study of the normal and pathological pancreas]. The renal pedicles were identified in 83.5% of pancreases during echotomography. The horizontal relations together with the vertical relations represented by the abdominal aorta and inferior vena cava permit one to localise with precision the cephalic and corporeal parts of the pancreas for they are situated just in front. Analysis of the echostructure of the pancreas thus localised is greatly facilitated."}
{"id": "PMID:186898", "title": "[Conservative surgical treatment in stage 4 arteritis of the lower extremities. Apropos of 26 cases].", "content": "The authors report 26 cases (average age 69 years) of stage IV atheroma of the leg arteries for which a conservative surgical operation was attempted. Aortography (18 times) or femoral arteriography (8 times) were performed without difficulty before operation. During the same operation, a single procedure was performed in 15 cases, 2 or 3 procedures were performed in 11 cases. Thus were carried out: sympathectomy in 7 cases, endarterectomy in 8 cases, a by-pass operation in 23 cases. There were 4 deaths (15%) during the postoperative period. In 18 of the 22 patients who survived the operation, trophic disorders completely disappeared, and the functional result assessed with an average follow up of 15 months (1 to 25 months) on the degree of intermitent claudication was judged good or very good in 16 cases, mediocre in 2 cases. In 4 of these 22 patients, the trophic disorders persisted or reappeared in the short term and amputation was then carried out in 3 of these 4 cases. Conservative surgery remains possible and useful in stage IV arterial disease of the lower limbs. It is however important to operate early in the course of the disease after failure of adequate medical treatment.", "contents": "[Conservative surgical treatment in stage 4 arteritis of the lower extremities. Apropos of 26 cases]. The authors report 26 cases (average age 69 years) of stage IV atheroma of the leg arteries for which a conservative surgical operation was attempted. Aortography (18 times) or femoral arteriography (8 times) were performed without difficulty before operation. During the same operation, a single procedure was performed in 15 cases, 2 or 3 procedures were performed in 11 cases. Thus were carried out: sympathectomy in 7 cases, endarterectomy in 8 cases, a by-pass operation in 23 cases. There were 4 deaths (15%) during the postoperative period. In 18 of the 22 patients who survived the operation, trophic disorders completely disappeared, and the functional result assessed with an average follow up of 15 months (1 to 25 months) on the degree of intermitent claudication was judged good or very good in 16 cases, mediocre in 2 cases. In 4 of these 22 patients, the trophic disorders persisted or reappeared in the short term and amputation was then carried out in 3 of these 4 cases. Conservative surgery remains possible and useful in stage IV arterial disease of the lower limbs. It is however important to operate early in the course of the disease after failure of adequate medical treatment."}
{"id": "PMID:186899", "title": "[Hand, foot and mouth disease].", "content": "Two characteristic cases encountered in young adults led the authors to present the hand foot and mouth syndrome. They report the characteristic distribution and vesicular appearance of the lesions. The course was benign. The viral origin of the disease was more or less easily confirmed by cell culture, inoculation in new born mice and demonstration of antibodies. Usually the virus was a Coxackie A 16. However in one of the authors cases, an Echo 11 was demonstrated. The apparent rareness of the disease may be explained by lack of recognition.", "contents": "[Hand, foot and mouth disease]. Two characteristic cases encountered in young adults led the authors to present the hand foot and mouth syndrome. They report the characteristic distribution and vesicular appearance of the lesions. The course was benign. The viral origin of the disease was more or less easily confirmed by cell culture, inoculation in new born mice and demonstration of antibodies. Usually the virus was a Coxackie A 16. However in one of the authors cases, an Echo 11 was demonstrated. The apparent rareness of the disease may be explained by lack of recognition."}
{"id": "PMID:186904", "title": "Fatal adenovirus pneumonia: Clinical and pathological features.", "content": "A review of autopsies of 107 young children with pneumonia showed that 15 children (14%) had adenovirus infections, the diagnosis being based on characteristic histopathological and ultrastructural features in the lungs. Eleven (73%) of the cases of adenovirus infection followed on measles infection, and it is suggested that some became infected with adenovirus after admission to hospital. A review of clinical aspects revealed no unique features. Histopathological examination of tissues showed a common picture of necrotising bronchopneumonia, with minor degrees of rental tubular damage, infiltrates of large mononuclear cells in spleen and nodes, and an absence of lymphoid germinal centres. On light microscopy, \"rosette\" and \"smudge\" cells were seen in these cases, and two patterns of virus particle distribution in infected cells were seen ultrastructurally. It is postulated that \"smudge\" cells contain numerous crystalline viral arrays.", "contents": "Fatal adenovirus pneumonia: Clinical and pathological features. A review of autopsies of 107 young children with pneumonia showed that 15 children (14%) had adenovirus infections, the diagnosis being based on characteristic histopathological and ultrastructural features in the lungs. Eleven (73%) of the cases of adenovirus infection followed on measles infection, and it is suggested that some became infected with adenovirus after admission to hospital. A review of clinical aspects revealed no unique features. Histopathological examination of tissues showed a common picture of necrotising bronchopneumonia, with minor degrees of rental tubular damage, infiltrates of large mononuclear cells in spleen and nodes, and an absence of lymphoid germinal centres. On light microscopy, \"rosette\" and \"smudge\" cells were seen in these cases, and two patterns of virus particle distribution in infected cells were seen ultrastructurally. It is postulated that \"smudge\" cells contain numerous crystalline viral arrays."}
{"id": "PMID:186905", "title": "Time related response of urinary cyclic adenosine monophosphate to trauma.", "content": "Urinary cyclic adenosine monophosphate levels were measured in 150 patients with accidental injury of varying causes. Thirty-eight healthy adults of both sexes serving as controls excreted 2.21 to 6.85 micromoles of cyclic adenosine monomphosphate per gram of creatinine, mean 4.34 +/- 1.25. In 120 patients with trauma on admission, the excretion was increased by 15.7 per cent, p less than 0.05, and the changes showed a time related pattern. In patients admitted within the first 30, 60 and 120 minutes after trauma, the mean excretion was changed by 19, 10 and minus 2.8 per cent, respectively, and in those admitted between two and 24 hours by 30 per cent. Twelve patients with differing types of trauma showed a mean 24 hour excretion reaching its peak on the first day, 44 per cent, and declining to its nadir of 2.25 micromoles per gram of creatinine on the third day, minus 47 per cent, p less than 0.01. A second rise reached its peak on the fifth day, p less than 0.05. Thereafter, the excretion fluctuated widely with peaks significantly above and below the control range, and we were unable to correlate these changes with any specific factors. In post-traumatic acute renal failure, the nucleotide excretion fell within several hours and usually reached low values, that is, below 0.25 micromoles per 1,000 milliliters per 24 hours within one to three days. In general, the excretory pattern for cyclic adenosine monophosphate followed that of creatinine clearance, but in the diuretic phase of the recovering kidney, the cyclic adenosine monophosphate levels remained more depressed than those of creatinine. The high sensitivity of urinary cyclic adenosine monophosphate to abnormalities in renal function suggests its potential as a clinical indicator.", "contents": "Time related response of urinary cyclic adenosine monophosphate to trauma. Urinary cyclic adenosine monophosphate levels were measured in 150 patients with accidental injury of varying causes. Thirty-eight healthy adults of both sexes serving as controls excreted 2.21 to 6.85 micromoles of cyclic adenosine monomphosphate per gram of creatinine, mean 4.34 +/- 1.25. In 120 patients with trauma on admission, the excretion was increased by 15.7 per cent, p less than 0.05, and the changes showed a time related pattern. In patients admitted within the first 30, 60 and 120 minutes after trauma, the mean excretion was changed by 19, 10 and minus 2.8 per cent, respectively, and in those admitted between two and 24 hours by 30 per cent. Twelve patients with differing types of trauma showed a mean 24 hour excretion reaching its peak on the first day, 44 per cent, and declining to its nadir of 2.25 micromoles per gram of creatinine on the third day, minus 47 per cent, p less than 0.01. A second rise reached its peak on the fifth day, p less than 0.05. Thereafter, the excretion fluctuated widely with peaks significantly above and below the control range, and we were unable to correlate these changes with any specific factors. In post-traumatic acute renal failure, the nucleotide excretion fell within several hours and usually reached low values, that is, below 0.25 micromoles per 1,000 milliliters per 24 hours within one to three days. In general, the excretory pattern for cyclic adenosine monophosphate followed that of creatinine clearance, but in the diuretic phase of the recovering kidney, the cyclic adenosine monophosphate levels remained more depressed than those of creatinine. The high sensitivity of urinary cyclic adenosine monophosphate to abnormalities in renal function suggests its potential as a clinical indicator."}
{"id": "PMID:186908", "title": "Cultured cells in cystic fibrosis research: A review.", "content": "Cystic fibrosis (CF) is a common inherited disorder which is characterized by the production of exocrine secretions with elevated ion content and abnormally viscous mucus. Over the last few years cells obtained from the peripheral blood or cultured from tissues of cystic fibrosis patients have been used increasingly in the study of the disease. Investigations of the following properties of cystic fibrosis cells are reviewed: morphology, ultrastructure, growth kinetics, cellular metachromasia, the production of ciliary inhibitors, cellular composition, plasma membrane composition, the transport of inorganic ions and small organic molecules, lysosomal enzyme content, and RNA methylation. Studies of the effects on cultured cells and erythrocyte membranes of factors in CF cell culture medium and biological fluids from CF patients are discussed.", "contents": "Cultured cells in cystic fibrosis research: A review. Cystic fibrosis (CF) is a common inherited disorder which is characterized by the production of exocrine secretions with elevated ion content and abnormally viscous mucus. Over the last few years cells obtained from the peripheral blood or cultured from tissues of cystic fibrosis patients have been used increasingly in the study of the disease. Investigations of the following properties of cystic fibrosis cells are reviewed: morphology, ultrastructure, growth kinetics, cellular metachromasia, the production of ciliary inhibitors, cellular composition, plasma membrane composition, the transport of inorganic ions and small organic molecules, lysosomal enzyme content, and RNA methylation. Studies of the effects on cultured cells and erythrocyte membranes of factors in CF cell culture medium and biological fluids from CF patients are discussed."}
{"id": "PMID:186909", "title": "Immunochemical studies of the plasma and cultured fibroblast media fractions containing the cystic fibrosis ciliary inhibitor.", "content": "The cystic fibrosis ciliary inhibitor (CFCI) has been fractionated from plasma of cystic fibrosis (CF) homozygotes and from the media of cultured fibroblasts derived from CF homozygotes. Plasma and fibroblast media from normal controls have been fractionated in an identical manner. Fractions from plasma and fibroblast culture media that demonstrate ciliary inhibitory activity contain several proteins in a molecular weight range of approximately 5,000-11,000. These proteins have been partially characterized by immunochemical analysis with antisera to 33 human serum proteins. Immunological determinants of albumin, C3 (but not C3a), C4, C5, alpha1-lipoprotein, beta-lipoprotein, beta2-microglobulin and immunoglobulin light chains have been detected by hemagglutination in fractions of CF plasma that inhibited ciliary activity and in analogous fractions from normal sera. None of the proteins were detected in media of cultured fibroblasts from either genotype. Since the same proteins and protein fragments were identified in both CF and normal plasma fractions, and were not detected in CF fibroblast media, it appears that none of these proteins can be identified as the CFCI. Identification of these proteins will permit further purification of the CFCI by immunochemical methods.", "contents": "Immunochemical studies of the plasma and cultured fibroblast media fractions containing the cystic fibrosis ciliary inhibitor. The cystic fibrosis ciliary inhibitor (CFCI) has been fractionated from plasma of cystic fibrosis (CF) homozygotes and from the media of cultured fibroblasts derived from CF homozygotes. Plasma and fibroblast media from normal controls have been fractionated in an identical manner. Fractions from plasma and fibroblast culture media that demonstrate ciliary inhibitory activity contain several proteins in a molecular weight range of approximately 5,000-11,000. These proteins have been partially characterized by immunochemical analysis with antisera to 33 human serum proteins. Immunological determinants of albumin, C3 (but not C3a), C4, C5, alpha1-lipoprotein, beta-lipoprotein, beta2-microglobulin and immunoglobulin light chains have been detected by hemagglutination in fractions of CF plasma that inhibited ciliary activity and in analogous fractions from normal sera. None of the proteins were detected in media of cultured fibroblasts from either genotype. Since the same proteins and protein fragments were identified in both CF and normal plasma fractions, and were not detected in CF fibroblast media, it appears that none of these proteins can be identified as the CFCI. Identification of these proteins will permit further purification of the CFCI by immunochemical methods."}
{"id": "PMID:186910", "title": "Surface enzymes in cultured fibroblasts from cystic fibrosis patients.", "content": "Membrane function was examined in cultured cells from cystic fibrosis patients by assaying several enzymes on intact skin fibroblasts attached to culture dishes. This technique required few cells and minimized disruption of cellular organization. Comparison of enzyme activities of intact and broken cells showed that 12% of total glucose-6-phosphate dehydrogenase, a cytoplasmic enzyme, was measurable using intact cells, while all adenosine monophosphatase was measurable using intact cells. Alkaline paranitrophenylphosphatase activity was divided between the cell surface and interior. Substrate competition experiments indicated that substrate specificities for adenosine monophosphatase and paranitrophenylphosphatase activities were different. Adenosine monophosphatase activities of 2 control and 2 cystic fibrosis strains fluctuated similarly during the cell culture cycle. The apparent Km values relative to adenosine monophosphate were similar in all strains. A chromatographic fraction of serum from a cystic fibrosis patient that was inhibitory to oyster ciliary activity had no effect on adenosine monophosphatase activity of normal fibroblasts. Furthermore, fractions of media from cystic fibrosis homozygote and heterozygote fibroblast cultures were not inhibitory to adenosine monophosphatase activities of intact normal fibroblasts or of part iculate fractions prepared from them. In light of previous studies that showed that factors from cystic fibrosis serum of culture medium disrupted specific membrane activities, it is proposed that the cystic fibrosis factor interacts with the plasma membrane, interfering most conspicuously with the protein functions that are sensitive to changes in their membrane environment.", "contents": "Surface enzymes in cultured fibroblasts from cystic fibrosis patients. Membrane function was examined in cultured cells from cystic fibrosis patients by assaying several enzymes on intact skin fibroblasts attached to culture dishes. This technique required few cells and minimized disruption of cellular organization. Comparison of enzyme activities of intact and broken cells showed that 12% of total glucose-6-phosphate dehydrogenase, a cytoplasmic enzyme, was measurable using intact cells, while all adenosine monophosphatase was measurable using intact cells. Alkaline paranitrophenylphosphatase activity was divided between the cell surface and interior. Substrate competition experiments indicated that substrate specificities for adenosine monophosphatase and paranitrophenylphosphatase activities were different. Adenosine monophosphatase activities of 2 control and 2 cystic fibrosis strains fluctuated similarly during the cell culture cycle. The apparent Km values relative to adenosine monophosphate were similar in all strains. A chromatographic fraction of serum from a cystic fibrosis patient that was inhibitory to oyster ciliary activity had no effect on adenosine monophosphatase activity of normal fibroblasts. Furthermore, fractions of media from cystic fibrosis homozygote and heterozygote fibroblast cultures were not inhibitory to adenosine monophosphatase activities of intact normal fibroblasts or of part iculate fractions prepared from them. In light of previous studies that showed that factors from cystic fibrosis serum of culture medium disrupted specific membrane activities, it is proposed that the cystic fibrosis factor interacts with the plasma membrane, interfering most conspicuously with the protein functions that are sensitive to changes in their membrane environment."}
{"id": "PMID:186911", "title": "Diagnostic value of serum angiotensin converting enzyme activity in lung diseases.", "content": "Serum angiotensin converting enzyme (ACE) activity was measured in 10 patients with early active sarcoidosis, nine patients with inactive or resolving sarcoidosis, 10 patients with malignant pulmonary neoplasms, eight patients with miscellaneous lung diseases, and 18 control subjects with no known pulmonary disease. The serum ACE activity, expressed in units/ml, in control subjects (5-88 +/- 1-84), was no different from the values obtained in patients with inactive or resolving sarcoidosis (6-85 +/- 2-48) or miscellaneous lung diseases (4-61 +/- 3-20). However, the ACE activity was found to be markedly raised in patients with early active sarcoidosis (13-49 +/- 2-52), and there was no overlap with control values. The patients with pulmonary neoplasms had significantly lower values of serum ACE activity than the control subjects (2-80 +/- 3-30).", "contents": "Diagnostic value of serum angiotensin converting enzyme activity in lung diseases. Serum angiotensin converting enzyme (ACE) activity was measured in 10 patients with early active sarcoidosis, nine patients with inactive or resolving sarcoidosis, 10 patients with malignant pulmonary neoplasms, eight patients with miscellaneous lung diseases, and 18 control subjects with no known pulmonary disease. The serum ACE activity, expressed in units/ml, in control subjects (5-88 +/- 1-84), was no different from the values obtained in patients with inactive or resolving sarcoidosis (6-85 +/- 2-48) or miscellaneous lung diseases (4-61 +/- 3-20). However, the ACE activity was found to be markedly raised in patients with early active sarcoidosis (13-49 +/- 2-52), and there was no overlap with control values. The patients with pulmonary neoplasms had significantly lower values of serum ACE activity than the control subjects (2-80 +/- 3-30)."}
{"id": "PMID:186914", "title": "Effects of subsacute and chronic lead treatment on glucose homeostasis and renal cyclic AMP metabolism in rats.", "content": "The effects of chronic oral ingestion of lead in doses ranging from 20-80 ppm were compared with those seen after the subacute exposure of rats to a 10 mg/kg daily dose of the heavy metal for 7 days. Irrespective of the treatment regimen used, lead treatment significantly increased the activities of renal pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase. The observed enhancement of kidney gluconeogenic enzymes in chronically treated animals was associated with a stimulation of the adenylate cyclase-cyclic AMP system, a rise in blood blucose and urea as well as a depression in hepatic glycogen and serum immunoreactive insulin (IRI) levels. In contrast, subacute exposure to lead failed to significantly alter cyclic AMP metabolism and the concentrations of liver glycogen, blood glucose, serum urea or IRI. Whwereas the insulinogenic index (the ratio of serum IRI to blood glucose concentration) was markedly suppressed in chronically treated rats, this ratio remained within normal limits following subacute exposure to the heavy metal. However, a marked decrease in the insulinogenic index was observed in subacutely treated rats 15 min after the administration of a glucose load. The data provide evidence to show that increased glucose synthesis as well as suppressed pancreatic function may be responsible for lead-induced disturbances in glucose homeostasis.", "contents": "Effects of subsacute and chronic lead treatment on glucose homeostasis and renal cyclic AMP metabolism in rats. The effects of chronic oral ingestion of lead in doses ranging from 20-80 ppm were compared with those seen after the subacute exposure of rats to a 10 mg/kg daily dose of the heavy metal for 7 days. Irrespective of the treatment regimen used, lead treatment significantly increased the activities of renal pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase. The observed enhancement of kidney gluconeogenic enzymes in chronically treated animals was associated with a stimulation of the adenylate cyclase-cyclic AMP system, a rise in blood blucose and urea as well as a depression in hepatic glycogen and serum immunoreactive insulin (IRI) levels. In contrast, subacute exposure to lead failed to significantly alter cyclic AMP metabolism and the concentrations of liver glycogen, blood glucose, serum urea or IRI. Whwereas the insulinogenic index (the ratio of serum IRI to blood glucose concentration) was markedly suppressed in chronically treated rats, this ratio remained within normal limits following subacute exposure to the heavy metal. However, a marked decrease in the insulinogenic index was observed in subacutely treated rats 15 min after the administration of a glucose load. The data provide evidence to show that increased glucose synthesis as well as suppressed pancreatic function may be responsible for lead-induced disturbances in glucose homeostasis."}
{"id": "PMID:186921", "title": "Nodular renal blastema, nephroblastomatosis, and Wilms' tumor. Different points on the same disease spectrum?", "content": "A case of nodular renal blastema developing into nephroblastomatosis is presented. Definitions and histopathology of these entities is given, and it is suggested that they represent a developmental spectrum with natural progression to Wilms' tumor.", "contents": "Nodular renal blastema, nephroblastomatosis, and Wilms' tumor. Different points on the same disease spectrum? A case of nodular renal blastema developing into nephroblastomatosis is presented. Definitions and histopathology of these entities is given, and it is suggested that they represent a developmental spectrum with natural progression to Wilms' tumor."}
{"id": "PMID:186926", "title": "[Hepatic tissue respiration in pathology of the biliary system and the effect of hyperbaric oxygenation on the course of hepatic insufficiency].", "content": "Under study was the effect of hyperbaric oxygenation in 46 patients on the course of bile tract diseases, complicated with hepatic insufficiency. Hyperbaric oxygenation was found to render a positive effect on the course of hepatic insufficiency.", "contents": "[Hepatic tissue respiration in pathology of the biliary system and the effect of hyperbaric oxygenation on the course of hepatic insufficiency]. Under study was the effect of hyperbaric oxygenation in 46 patients on the course of bile tract diseases, complicated with hepatic insufficiency. Hyperbaric oxygenation was found to render a positive effect on the course of hepatic insufficiency."}
{"id": "PMID:186932", "title": "Immunosuppressive effect of a naturally acquired subclinical bursal agent infection on vaccination against Newcastle disease.", "content": "A naturally acquired subclinical infection of infectious bursal agent was shown to be the probable causative factor of marked immunosuppression of Newcastle disease vaccine in young chicks. Old hens maintained in the same contaminated environment did not exhibit immunosuppression.", "contents": "Immunosuppressive effect of a naturally acquired subclinical bursal agent infection on vaccination against Newcastle disease. A naturally acquired subclinical infection of infectious bursal agent was shown to be the probable causative factor of marked immunosuppression of Newcastle disease vaccine in young chicks. Old hens maintained in the same contaminated environment did not exhibit immunosuppression."}
{"id": "PMID:186941", "title": "[Concentration of different forms of RNA in the brain and ribonuclease activity of the nuclear, ribosomal and supernatant fractions of brain tissue following the action of cyclic adenosine-3',5'-monophosphate and S-adenosyl-L-methionine].", "content": "Quantitative changes of various forms of ribonucleic acids [nuclear (n-RNA), ribosomal (r-RNA), transport (t-RNA)] as well as ribonuclease activity have been studied in rat brain, in its nuclear, ribosomal and supernatant fractions following 3,5-cyclic AMP (c-AMP) and S-adenosyl-L-methionine. These substances were shown to raise the levels of r-RNA in brain and reduce the amount of n-RNA of GC type. c-AMP was also found to reduce the n-RNA of AU type and t-RNA in brain, while S-adenosyl-L-methionine does not affect n-RNA of AU type and raises considerably t-RNA. S-adenosyl-L-methionine has been found to raise the levels of all kinds of RNA while c-AMP has no effect. Ribonuclease activity of nuclear, ribosomal and supernatant fractions (105,000 g) of brain has been found to be enhanced by c-AMP while S-adenosyl-L-methionine raises ribonuclease activity of ribosomal fraction only at pH 7.9. The data obtained indicate that c-AMP and S-adenosyl-L-methionine are of importance in the mechanisms regulating the level of nucleic acids and activity of enzymes involved in their metabolism.", "contents": "[Concentration of different forms of RNA in the brain and ribonuclease activity of the nuclear, ribosomal and supernatant fractions of brain tissue following the action of cyclic adenosine-3',5'-monophosphate and S-adenosyl-L-methionine]. Quantitative changes of various forms of ribonucleic acids [nuclear (n-RNA), ribosomal (r-RNA), transport (t-RNA)] as well as ribonuclease activity have been studied in rat brain, in its nuclear, ribosomal and supernatant fractions following 3,5-cyclic AMP (c-AMP) and S-adenosyl-L-methionine. These substances were shown to raise the levels of r-RNA in brain and reduce the amount of n-RNA of GC type. c-AMP was also found to reduce the n-RNA of AU type and t-RNA in brain, while S-adenosyl-L-methionine does not affect n-RNA of AU type and raises considerably t-RNA. S-adenosyl-L-methionine has been found to raise the levels of all kinds of RNA while c-AMP has no effect. Ribonuclease activity of nuclear, ribosomal and supernatant fractions (105,000 g) of brain has been found to be enhanced by c-AMP while S-adenosyl-L-methionine raises ribonuclease activity of ribosomal fraction only at pH 7.9. The data obtained indicate that c-AMP and S-adenosyl-L-methionine are of importance in the mechanisms regulating the level of nucleic acids and activity of enzymes involved in their metabolism."}
{"id": "PMID:186942", "title": "[Role of adenine mono- and dinucleotides in ammonia formation in brain tissue].", "content": "The investigations carried out have shown that not only AMP but ADP also undergoes direct deamination in both soluble and mitochondrial fractions of rat brain tissue. Deamination of AMP is stimulated by the addition of ATP and the activity of one of the isoenzymes of AMP-aminohydrolase is markedly enhanced by both yeast and brain hexokinase. Activation by hexokinase is mainly due to its SH groups, through which hexokinase reacts with AMP-aminohydrolase, forming, probably, a protein-protein complex in which AMP aminohydrolase activity is considerably increased. Hexokinase does not affect the deamination of ADP and NAD. Further experiments are needed to find out whether the activation of AMP-aminohydrolase is accomplished by hexokinase itself or by an other protein contaminating it. Deamination of NAD, in contrast to AMP and ADP, takes place only in mitochondria and does not occur in the soluble fraction. In mitochondria besides deamination, AMP and ADP undergo intensive dephosphorylation, while the deamination of NAD is not accompanied by an increase of phosphate, i. e. mitochondria lack enzymes which breakdown NAD to mono nucleotides. Our data indicate that the formation of deamino -NAD from NAD and reamination of deamino-NAD by aspartate to NAD by the formation of intermediary NAD-succinate is of greater importance. The formation of the latter and that of deamino-NAD from NAD as well as the presence of preformed deamino-NAD in mitochondria have been demonstrated by Movsessian. The occurrence of these processes in mitochondria and their role in the formation of ammonia from amino acids is of importance in as much as oxaloacetate formation and its conversion to aspartate, which is necessary for the reamination of deamino-NAD, are localized in mitochondria. The main source of the amino nitrogen of aspartate is known to be glutamate, which incorporates the amino nitrogen of most amino acids. alpha-Keto-glutarate, which is necessary  for the synthesis of glutamate, is also formed in mitochondria are the most favourable site for the formation of ammonia from amino acids with the participation of pyridine nucleotides. Of the purine mono and dinucleotides studied deamino-NAD is most effective in the formation of ammonia from amino acids in mitochondria since in contrast to purine mono nucleotides, deamino-NAD and NAD are not dephosphorylated in mitochondria. According to some authors the reamination of IMP by aspartate is of importance in the formation of ammonia from amino acids in brain tissue. In our studies, however, IMP was not effective in the formation of ammonia from aspartate in mitochondrial fractions. IDP was found to be more effective. IMP and IDP may probably participate in the formation of ammonia in the soluble fraction, where nucleotidase activity is considerably low.", "contents": "[Role of adenine mono- and dinucleotides in ammonia formation in brain tissue]. The investigations carried out have shown that not only AMP but ADP also undergoes direct deamination in both soluble and mitochondrial fractions of rat brain tissue. Deamination of AMP is stimulated by the addition of ATP and the activity of one of the isoenzymes of AMP-aminohydrolase is markedly enhanced by both yeast and brain hexokinase. Activation by hexokinase is mainly due to its SH groups, through which hexokinase reacts with AMP-aminohydrolase, forming, probably, a protein-protein complex in which AMP aminohydrolase activity is considerably increased. Hexokinase does not affect the deamination of ADP and NAD. Further experiments are needed to find out whether the activation of AMP-aminohydrolase is accomplished by hexokinase itself or by an other protein contaminating it. Deamination of NAD, in contrast to AMP and ADP, takes place only in mitochondria and does not occur in the soluble fraction. In mitochondria besides deamination, AMP and ADP undergo intensive dephosphorylation, while the deamination of NAD is not accompanied by an increase of phosphate, i. e. mitochondria lack enzymes which breakdown NAD to mono nucleotides. Our data indicate that the formation of deamino -NAD from NAD and reamination of deamino-NAD by aspartate to NAD by the formation of intermediary NAD-succinate is of greater importance. The formation of the latter and that of deamino-NAD from NAD as well as the presence of preformed deamino-NAD in mitochondria have been demonstrated by Movsessian. The occurrence of these processes in mitochondria and their role in the formation of ammonia from amino acids is of importance in as much as oxaloacetate formation and its conversion to aspartate, which is necessary for the reamination of deamino-NAD, are localized in mitochondria. The main source of the amino nitrogen of aspartate is known to be glutamate, which incorporates the amino nitrogen of most amino acids. alpha-Keto-glutarate, which is necessary  for the synthesis of glutamate, is also formed in mitochondria are the most favourable site for the formation of ammonia from amino acids with the participation of pyridine nucleotides. Of the purine mono and dinucleotides studied deamino-NAD is most effective in the formation of ammonia from amino acids in mitochondria since in contrast to purine mono nucleotides, deamino-NAD and NAD are not dephosphorylated in mitochondria. According to some authors the reamination of IMP by aspartate is of importance in the formation of ammonia from amino acids in brain tissue. In our studies, however, IMP was not effective in the formation of ammonia from aspartate in mitochondrial fractions. IDP was found to be more effective. IMP and IDP may probably participate in the formation of ammonia in the soluble fraction, where nucleotidase activity is considerably low."}
{"id": "PMID:186943", "title": "[Soluble cerebral metalloproteins. 1. Purification and properties of cerebral cortex cytochrome c].", "content": "Cytochrome c from grey matter of brain has been obtained as a homogeneous preparation by electrophoresis on polyacrylamide gel and following electrofocusing in ampholine solutions. Its molecular weight, content of iron, redox potential and isoelectric point have been established. The absolute spectra of its oxidized and reduced forms are presented. Cytochrome c of brain cortex is similar in its properties to that obtained from other animal tissues as the heart and adrenal cortex.", "contents": "[Soluble cerebral metalloproteins. 1. Purification and properties of cerebral cortex cytochrome c]. Cytochrome c from grey matter of brain has been obtained as a homogeneous preparation by electrophoresis on polyacrylamide gel and following electrofocusing in ampholine solutions. Its molecular weight, content of iron, redox potential and isoelectric point have been established. The absolute spectra of its oxidized and reduced forms are presented. Cytochrome c of brain cortex is similar in its properties to that obtained from other animal tissues as the heart and adrenal cortex."}
{"id": "PMID:186944", "title": "[Coenzyme specificity and isoenzyme spectrum of lactate dehydrogenase from different regions of the brain].", "content": "The coenzyme affinity of lactate dehydrogenase of various parts of rat brain is different to deamino-NAD and NAD as well as to their reduced forms. In direct reactions NAD exhibits a higher activity than deamino-NAD. In the reverse reaction an opposite pattern is observed. The effect of deamino-NADH is much higher than that of NADH. Our studies have shown that the isoenzymes of LDH which are richer in H subunits have a higher affinity for deamino-NAD and deamino-NADH than for NAD and NADH. The isoenzymes of LDH that contain more M forms have opposite properties. LDH-3 does not show a pronounced selective affinity. The data obtained indicate that the activity of LDH and of its 5 isoenzymes varies greatly in different brain parts; crucial changes being observed in the relative percentage of molecular forms of LDH.", "contents": "[Coenzyme specificity and isoenzyme spectrum of lactate dehydrogenase from different regions of the brain]. The coenzyme affinity of lactate dehydrogenase of various parts of rat brain is different to deamino-NAD and NAD as well as to their reduced forms. In direct reactions NAD exhibits a higher activity than deamino-NAD. In the reverse reaction an opposite pattern is observed. The effect of deamino-NADH is much higher than that of NADH. Our studies have shown that the isoenzymes of LDH which are richer in H subunits have a higher affinity for deamino-NAD and deamino-NADH than for NAD and NADH. The isoenzymes of LDH that contain more M forms have opposite properties. LDH-3 does not show a pronounced selective affinity. The data obtained indicate that the activity of LDH and of its 5 isoenzymes varies greatly in different brain parts; crucial changes being observed in the relative percentage of molecular forms of LDH."}
{"id": "PMID:186945", "title": "[Coenzyme specificity and isoenzyme spectrum of rat brain malate dehydrogenase].", "content": "Our studies have shown that malatedehydrogenase of rat brain mitochondrial fraction (M-MDH) and soluble fraction (S-MDH) differ in respect to their coenzyme specificity. Affinity of both M-MDH and S-MDH to deamino-NAD (direct reaction) is about two times lower than toward NAD. In the reverse reaction deamino-NADH and NADH enhance the activity of M-MDH to the same extent while in the presence of deamino-NADH the activity of S-MDH is somewhat higher. The isoenzyme composition of M-MDH and S-MDH have been studied as well as the relative affinity of each isoenzyme towards deamino-NAD and NAD. Both M-MDH and S-MDH have been shown to consist of 3 isoenzymes, the second isoenzyme being the most active. The percentage of the 3-rd isoenzyme is the lowest. The coenzyme affinity of isoenzymes M-MDH and S-MDH have been shown to differ very markedly.", "contents": "[Coenzyme specificity and isoenzyme spectrum of rat brain malate dehydrogenase]. Our studies have shown that malatedehydrogenase of rat brain mitochondrial fraction (M-MDH) and soluble fraction (S-MDH) differ in respect to their coenzyme specificity. Affinity of both M-MDH and S-MDH to deamino-NAD (direct reaction) is about two times lower than toward NAD. In the reverse reaction deamino-NADH and NADH enhance the activity of M-MDH to the same extent while in the presence of deamino-NADH the activity of S-MDH is somewhat higher. The isoenzyme composition of M-MDH and S-MDH have been studied as well as the relative affinity of each isoenzyme towards deamino-NAD and NAD. Both M-MDH and S-MDH have been shown to consist of 3 isoenzymes, the second isoenzyme being the most active. The percentage of the 3-rd isoenzyme is the lowest. The coenzyme affinity of isoenzymes M-MDH and S-MDH have been shown to differ very markedly."}
{"id": "PMID:186949", "title": "[Course and outcome of treatment of synovial sarcoma].", "content": "The results of exploration of 126 patients with synovial sarcoma are reported; males -- 70, females -- 54, aged from 4 to 74 years old. The tumor was found to be localized as follows: the extremities -- 117 (upper -- 33, lower -- 84), and the body -- 9 patients. Seven structural variants of synovial sarcoma were differentiated: 1) alveolar -- 19, 2) adenomatous -- 10, 3) histioid -- 65, 4) perithelial --3, 5) fibrous -- 6, 6) gigantic-cell -- 3 and 7) mixed -- 20 patients. The patients were treated surgically (56 patients) and using the combined technics (70 patients). The most favourable results were noted in treatment of patients with adenomatous and fibrous types of synovial sarcoma, worse issues -- in patients with gigantic-cell and perithelial forms. Synovial sarcomas of histioid and mixed types occupy the intermediate place. The most malignant character of the neoplasm was observed in patients with alveolar tumor.", "contents": "[Course and outcome of treatment of synovial sarcoma]. The results of exploration of 126 patients with synovial sarcoma are reported; males -- 70, females -- 54, aged from 4 to 74 years old. The tumor was found to be localized as follows: the extremities -- 117 (upper -- 33, lower -- 84), and the body -- 9 patients. Seven structural variants of synovial sarcoma were differentiated: 1) alveolar -- 19, 2) adenomatous -- 10, 3) histioid -- 65, 4) perithelial --3, 5) fibrous -- 6, 6) gigantic-cell -- 3 and 7) mixed -- 20 patients. The patients were treated surgically (56 patients) and using the combined technics (70 patients). The most favourable results were noted in treatment of patients with adenomatous and fibrous types of synovial sarcoma, worse issues -- in patients with gigantic-cell and perithelial forms. Synovial sarcomas of histioid and mixed types occupy the intermediate place. The most malignant character of the neoplasm was observed in patients with alveolar tumor."}
{"id": "PMID:186950", "title": "[X-ray contrast and radioisotope angiography in tumors of the neck].", "content": "Comparative results of angiography and radioisotope scintigraphy with technetium (Tc 99 m) in 38 patients having different jugular tumors are reported. Both methods were found to correlate well with respect to the estimation of tutor blood supply. Radioisotope scintigraphy is a more simple, physiological and practically safe method of investigation, and the former should be recommended for estimating the degree of tumors vascularization, the state of brain circulation and also in cases when angiography proves to be unfeasible.", "contents": "[X-ray contrast and radioisotope angiography in tumors of the neck]. Comparative results of angiography and radioisotope scintigraphy with technetium (Tc 99 m) in 38 patients having different jugular tumors are reported. Both methods were found to correlate well with respect to the estimation of tutor blood supply. Radioisotope scintigraphy is a more simple, physiological and practically safe method of investigation, and the former should be recommended for estimating the degree of tumors vascularization, the state of brain circulation and also in cases when angiography proves to be unfeasible."}
{"id": "PMID:186951", "title": "[Transport of heterologous DNA in normal and tumor cells and its modification by radiation].", "content": "The authors have studied in a comparative way the kinetics of incorporation of labelled heterologous DNA in tumor and nontumor cells of an identical histological type, obtained from non-irradiated and irradiated with 800 rad rats. It has been shown that the process of incorporation of heterologous high-polymer DNA in cells is somewhat undulatory, and its temporal characteristics and level -- tissue-specific. Difference between tumor cells and their normal prototype show a quantitative character, conditioned by a large surface area. 30 minutes following the irradiation qualitative changes opposite for both kinds of cells were observed in the kinetics of incorporation: an acceleration for lymphoyctes and retardation for Pliss lymphosarcoma and Zajdela hepatoma cells.", "contents": "[Transport of heterologous DNA in normal and tumor cells and its modification by radiation]. The authors have studied in a comparative way the kinetics of incorporation of labelled heterologous DNA in tumor and nontumor cells of an identical histological type, obtained from non-irradiated and irradiated with 800 rad rats. It has been shown that the process of incorporation of heterologous high-polymer DNA in cells is somewhat undulatory, and its temporal characteristics and level -- tissue-specific. Difference between tumor cells and their normal prototype show a quantitative character, conditioned by a large surface area. 30 minutes following the irradiation qualitative changes opposite for both kinds of cells were observed in the kinetics of incorporation: an acceleration for lymphoyctes and retardation for Pliss lymphosarcoma and Zajdela hepatoma cells."}
{"id": "PMID:186952", "title": "[Effect of alkylating chemical substances on the activity and molecular heterogeneity of mouse sarcoma 180 nucleoside phosphate kinases].", "content": "The fractionation of extracts from sarcoma 180 cells was carried out on DEAE-cellulose following the administration to tumor-bearing mice of one of chloroctyl amino-phenildioxan derivatives. The tumor regression was noted more than in 50 per cent. It was found that the tumor regression, caused by this alkylating agent, results in marked changes in the fractionation pattern of thymidilatkinases. The origin of these changes is being discussed.", "contents": "[Effect of alkylating chemical substances on the activity and molecular heterogeneity of mouse sarcoma 180 nucleoside phosphate kinases]. The fractionation of extracts from sarcoma 180 cells was carried out on DEAE-cellulose following the administration to tumor-bearing mice of one of chloroctyl amino-phenildioxan derivatives. The tumor regression was noted more than in 50 per cent. It was found that the tumor regression, caused by this alkylating agent, results in marked changes in the fractionation pattern of thymidilatkinases. The origin of these changes is being discussed."}
{"id": "PMID:186953", "title": "[Heterogeneity of a population of the Kekaya strain of Marek disease virus].", "content": "While infecting VMD-Kekava chick fibroblasts cultures two plaque-forming variants of the virus were isolated. Both variants are cell-associated viruses; during a prolonged period these are circulating in the blood of infected chicks, including also healthy ones. The cultures infected contain a common precipitating antigen; sera from the infected chicks have antibodies to VMD feather antigen, both viruses produced, although in a different degree, in the infected chicks lymphoid infiltration of nerve trunks typical for Marek's disease. These variants differ one from the other in the type of plaques formed by them in the tissue culture, and in their pathogenicity for chicks. Variant 83 is likely to be naturally attenuated virus, and further on it may be investigated as a vaccine strain.", "contents": "[Heterogeneity of a population of the Kekaya strain of Marek disease virus]. While infecting VMD-Kekava chick fibroblasts cultures two plaque-forming variants of the virus were isolated. Both variants are cell-associated viruses; during a prolonged period these are circulating in the blood of infected chicks, including also healthy ones. The cultures infected contain a common precipitating antigen; sera from the infected chicks have antibodies to VMD feather antigen, both viruses produced, although in a different degree, in the infected chicks lymphoid infiltration of nerve trunks typical for Marek's disease. These variants differ one from the other in the type of plaques formed by them in the tissue culture, and in their pathogenicity for chicks. Variant 83 is likely to be naturally attenuated virus, and further on it may be investigated as a vaccine strain."}
{"id": "PMID:186954", "title": "[Excretion of cyclic adenosine monophosphate in breast and lung cancer].", "content": "The examination of over 150 human subjects failed to reveal any differences in the basal excretion of CAMP between breast cancer and lung cancer patients and the corresponding control. But breast cancer patients show certain disorders in the diurnal rhythm of CAMP production and also in the response of CAMP to euphylline, especially insulin. Moreover, a peculiar impairment of the coordination was noted between the state of fat-carbohydrate metabolism and the character of SAMP excretion in breast and lung cancer. The authors stress the necessity to study not only CAMP basal production in oncological patients but also its synthesis against the background of different functional stimuli and in measures aimed at the correction of disorders in fat-carbohydrate metabolism.", "contents": "[Excretion of cyclic adenosine monophosphate in breast and lung cancer]. The examination of over 150 human subjects failed to reveal any differences in the basal excretion of CAMP between breast cancer and lung cancer patients and the corresponding control. But breast cancer patients show certain disorders in the diurnal rhythm of CAMP production and also in the response of CAMP to euphylline, especially insulin. Moreover, a peculiar impairment of the coordination was noted between the state of fat-carbohydrate metabolism and the character of SAMP excretion in breast and lung cancer. The authors stress the necessity to study not only CAMP basal production in oncological patients but also its synthesis against the background of different functional stimuli and in measures aimed at the correction of disorders in fat-carbohydrate metabolism."}
{"id": "PMID:186955", "title": "[Extracellular nucleic acid in ascitic experimental tumors].", "content": "By using the phenol method, employed for obtaining RNA, the factor possessing electrophoretic mobility close to that of more rapidly migrating conformomer 5 S p-RNA and resistant to the action of pancreatic RNA-s was isolated from noncellular ascitic fluid, Ehrlich and NK/Ly tumors, hepatoma 22a, Zajdela hepatoma, ovarian ascites tumor in rats. This factor is suggested to participate in suppression of antitumor immunity in cancer.", "contents": "[Extracellular nucleic acid in ascitic experimental tumors]. By using the phenol method, employed for obtaining RNA, the factor possessing electrophoretic mobility close to that of more rapidly migrating conformomer 5 S p-RNA and resistant to the action of pancreatic RNA-s was isolated from noncellular ascitic fluid, Ehrlich and NK/Ly tumors, hepatoma 22a, Zajdela hepatoma, ovarian ascites tumor in rats. This factor is suggested to participate in suppression of antitumor immunity in cancer."}
{"id": "PMID:186956", "title": "[Effect of an additional whole-body irradiation on the induction of rat liver neoplasms by x-rays].", "content": "In direct single exposure of the rat liver to x-rays in the dosage to 4600 r cholangiocellular tumors were induced in 44.4% of animals. An additional total x-ray irradiation in rats in doses of 200 and 400 r increases the incidence of hepatic tumors up to 76.1 and 82.9% accordingly, shortens the latent period and contributes to the appearance of hepatic tumors of various genesis, including hepatocellular ones.", "contents": "[Effect of an additional whole-body irradiation on the induction of rat liver neoplasms by x-rays]. In direct single exposure of the rat liver to x-rays in the dosage to 4600 r cholangiocellular tumors were induced in 44.4% of animals. An additional total x-ray irradiation in rats in doses of 200 and 400 r increases the incidence of hepatic tumors up to 76.1 and 82.9% accordingly, shortens the latent period and contributes to the appearance of hepatic tumors of various genesis, including hepatocellular ones."}
{"id": "PMID:186957", "title": "[Carbohydrate metabolism in the kidneys of rats with dimethylnitrosamine-induced tumors].", "content": "Under study was anaerobic glycolysis, the activity of hexokinase, lactate dehydrogenase, gluco-6-phosphatase in rat kidneys in dimethylnitrosamine (DMNA) induced tumors in them. DMNA was administered perorally in the dosage of 10 mg/Kg during 4 weeks (25 mg per rat). Following 8 months tumors developed in the renal cortical substance. The tumor tissue, the renal cortical substance adjacent to the tumor, and the renal cortical substance without macroscopic tumor signs have been studied. An increased glycolysis, hexokinase and lactatedehydrogenase activity were noted, whereas the activity of glucoso-6-phosphatase was diminished in all tissues under examination. Changes of all indices were mostly pronounced in tumor tissue and least significant--in the renal cortical layer without any macroscopic tumor signs.", "contents": "[Carbohydrate metabolism in the kidneys of rats with dimethylnitrosamine-induced tumors]. Under study was anaerobic glycolysis, the activity of hexokinase, lactate dehydrogenase, gluco-6-phosphatase in rat kidneys in dimethylnitrosamine (DMNA) induced tumors in them. DMNA was administered perorally in the dosage of 10 mg/Kg during 4 weeks (25 mg per rat). Following 8 months tumors developed in the renal cortical substance. The tumor tissue, the renal cortical substance adjacent to the tumor, and the renal cortical substance without macroscopic tumor signs have been studied. An increased glycolysis, hexokinase and lactatedehydrogenase activity were noted, whereas the activity of glucoso-6-phosphatase was diminished in all tissues under examination. Changes of all indices were mostly pronounced in tumor tissue and least significant--in the renal cortical layer without any macroscopic tumor signs."}
{"id": "PMID:186959", "title": "[Sudden deafness and virus infection (author's transl)].", "content": "A survey of the literature concerning sudden deafness caused by virus infection is followed by a discussion of 46 patients with the history of acute loss of hearing, who were subjected to virological-serological examination. In 9 patients the titre movement of the complement fixation reaction was regarded to imply a viral cause of the acute loss of hearing. This was corroborated in 5 cases by the history of recent viral infection. Pathogenetically, the significance of the viral endolymphatic labyrinthitis was underlined. The success of traditional therapy did not differ from the results in cases of sudden deafness due to factors other than viral disease. In the absence of specific therapy the importance of prophylactic measures is stressed.", "contents": "[Sudden deafness and virus infection (author's transl)]. A survey of the literature concerning sudden deafness caused by virus infection is followed by a discussion of 46 patients with the history of acute loss of hearing, who were subjected to virological-serological examination. In 9 patients the titre movement of the complement fixation reaction was regarded to imply a viral cause of the acute loss of hearing. This was corroborated in 5 cases by the history of recent viral infection. Pathogenetically, the significance of the viral endolymphatic labyrinthitis was underlined. The success of traditional therapy did not differ from the results in cases of sudden deafness due to factors other than viral disease. In the absence of specific therapy the importance of prophylactic measures is stressed."}
{"id": "PMID:186960", "title": "[Virological investigations in peripheral idiopathic facial pareses (author's transl)].", "content": "Virological investigations were carried out on the serum of 62 patients suffering from peripheral facial pareses. The aetiology was definitely attributable to a virus infection in 12 of these cases. Neuropathological changes induced by these neurotropic viruses, predisposing anatomical features and pathogenesis are discussed. Since only symptomatic treatment is possible, the importance of active immunization, where available, is stressed in the prevention of virus diseases; a decrease in morbidity could lead to a reduction in neurological complications.", "contents": "[Virological investigations in peripheral idiopathic facial pareses (author's transl)]. Virological investigations were carried out on the serum of 62 patients suffering from peripheral facial pareses. The aetiology was definitely attributable to a virus infection in 12 of these cases. Neuropathological changes induced by these neurotropic viruses, predisposing anatomical features and pathogenesis are discussed. Since only symptomatic treatment is possible, the importance of active immunization, where available, is stressed in the prevention of virus diseases; a decrease in morbidity could lead to a reduction in neurological complications."}
{"id": "PMID:186961", "title": "[Angiopasm and lesion of the ulnar nerve in Dupuytren's contracture (author's transl)].", "content": "30 patients with Dupuytren's contracture were investigated by venous occlusion plethysmography of the index and ring fingers of both hands. The results are evaluated in respect to the clinical and electroneurophysiological findings. Special attention was given to the blood flow disturbances which have plethysmographically appeared to be a significant feature of Dupuytren's contracture and also to ulnar nerve lesions in individual cases. The finger venous occlusion plethysmography technique of Goetz (1934) has been further developed and a suitable apparatus constructed for the purpose of these investigations. Temporary vasopasm occurs in 77% of the patients suffering from Dupuytren's contracture when the fingers are cooled to 15 degrees C and a significant diminution of blood flow, as in the Raynaud syndrome, is evident. These neurovascular changes always appeared on the fingers of both hands and were similarly found in the region of the median nerve and of the ulnar nerve. They did not depend on the localization or the stage of the disease. 68% of the patients had symptoms suggestive of an ulnar nerve lesion, which corresponds with the findings of Mumenthaler (1961). In a comparison of the patients with normal plethysmographical findings and the patients with vasospasm, there is no correlation with the accompanying ulnar lesion. It is, thus, suggested that temporary vasopasm is not a consequence of the ulnar nerve lesion, but is related to an independent constitutional factor. In view of the high incidence of the ulnar lesion in patients with Dupuytren's contracture, a special neurological investigation is recommended and appropriate therapy, in addition to the fasiectomy, must be undertaken.", "contents": "[Angiopasm and lesion of the ulnar nerve in Dupuytren's contracture (author's transl)]. 30 patients with Dupuytren's contracture were investigated by venous occlusion plethysmography of the index and ring fingers of both hands. The results are evaluated in respect to the clinical and electroneurophysiological findings. Special attention was given to the blood flow disturbances which have plethysmographically appeared to be a significant feature of Dupuytren's contracture and also to ulnar nerve lesions in individual cases. The finger venous occlusion plethysmography technique of Goetz (1934) has been further developed and a suitable apparatus constructed for the purpose of these investigations. Temporary vasopasm occurs in 77% of the patients suffering from Dupuytren's contracture when the fingers are cooled to 15 degrees C and a significant diminution of blood flow, as in the Raynaud syndrome, is evident. These neurovascular changes always appeared on the fingers of both hands and were similarly found in the region of the median nerve and of the ulnar nerve. They did not depend on the localization or the stage of the disease. 68% of the patients had symptoms suggestive of an ulnar nerve lesion, which corresponds with the findings of Mumenthaler (1961). In a comparison of the patients with normal plethysmographical findings and the patients with vasospasm, there is no correlation with the accompanying ulnar lesion. It is, thus, suggested that temporary vasopasm is not a consequence of the ulnar nerve lesion, but is related to an independent constitutional factor. In view of the high incidence of the ulnar lesion in patients with Dupuytren's contracture, a special neurological investigation is recommended and appropriate therapy, in addition to the fasiectomy, must be undertaken."}
{"id": "PMID:186964", "title": "[Activation of vitamin D 3 and the mode of action of 1,25-hydroxycholecalciferol and 24,25-hydroxycholecalciferol].", "content": "A survey is given on the present state of the animal-biochemical research concerning the effectivity of the D-vitamins. The vitamin D3 is transferred in 25-hydroxycholecalciferol in the microsome fraction of the liver. Then in the kidneys a transformation into the physiologically active forms - the 1,25- and the 24,25-hydroxycholecalciferol - takes place. The kind of transformation depends on the Ca- and P-supply as well as on the level of the parathormone secretion. In the mucous membrane of the small intestine the 1,25- and the 24,25-hydroxycholecalciferol stimulate the formation of the Ca-transport protein. The 1,25-hydroxycholecalciferol is above all formed in hypocalcaemia or hypophosphataemia and furthers the mobilisation of Ca- and phosphate-ions from the bones. In a liver damage disturbances of the formation of 25-hydroxycholecalciferol and in renal damage disturbances of the formation of 1,25- and 24,25-hydroxycholecalciferol may appear. A reduction of the formation of the active forms of the D-vitamins leads to a decrease of the Ca-utilisation as well as of the growth of bones.", "contents": "[Activation of vitamin D 3 and the mode of action of 1,25-hydroxycholecalciferol and 24,25-hydroxycholecalciferol]. A survey is given on the present state of the animal-biochemical research concerning the effectivity of the D-vitamins. The vitamin D3 is transferred in 25-hydroxycholecalciferol in the microsome fraction of the liver. Then in the kidneys a transformation into the physiologically active forms - the 1,25- and the 24,25-hydroxycholecalciferol - takes place. The kind of transformation depends on the Ca- and P-supply as well as on the level of the parathormone secretion. In the mucous membrane of the small intestine the 1,25- and the 24,25-hydroxycholecalciferol stimulate the formation of the Ca-transport protein. The 1,25-hydroxycholecalciferol is above all formed in hypocalcaemia or hypophosphataemia and furthers the mobilisation of Ca- and phosphate-ions from the bones. In a liver damage disturbances of the formation of 25-hydroxycholecalciferol and in renal damage disturbances of the formation of 1,25- and 24,25-hydroxycholecalciferol may appear. A reduction of the formation of the active forms of the D-vitamins leads to a decrease of the Ca-utilisation as well as of the growth of bones."}
{"id": "PMID:186965", "title": "[Age-dependence of catecholamine effect in man. III. Influence of alpha- and beta-adrenergic agents on the lipolysis in the adipose tissue in vitro].", "content": "With the help of subcutaneous adipose tissue performed on 0,1- to 10-, 20- to 40- and 60- to 75-year-old test persons the effect of isoprenalin, adrenalin and noradrenalin on the release of glycerol or the unesterified fatty acids was investigated. Independent on age the quantity of the isoprenalin-stimulated lipolysis increases with the size of the fatty acids of the incubated tissues. The specimens of adipose tissue used do not show any differences in the size of the adipocytes between the individual age groups. Amaximum release of glycerol is achieved in a concentration of the medium of 10(-5) mol/l (isopernalin) to 10(-4) mol/l (adrenalin). Isopernalin effects an altogether larger increase of lipolysis in the adipose tissue of the human being of old age in already smaller concentrations compared with other age groups. These findings refer to a higher affinity of adrenergic beta-receptors of the adipocytes in this age period, but also to possible age differences in the chain of lipolysis mediated by cAMP.", "contents": "[Age-dependence of catecholamine effect in man. III. Influence of alpha- and beta-adrenergic agents on the lipolysis in the adipose tissue in vitro]. With the help of subcutaneous adipose tissue performed on 0,1- to 10-, 20- to 40- and 60- to 75-year-old test persons the effect of isoprenalin, adrenalin and noradrenalin on the release of glycerol or the unesterified fatty acids was investigated. Independent on age the quantity of the isoprenalin-stimulated lipolysis increases with the size of the fatty acids of the incubated tissues. The specimens of adipose tissue used do not show any differences in the size of the adipocytes between the individual age groups. Amaximum release of glycerol is achieved in a concentration of the medium of 10(-5) mol/l (isopernalin) to 10(-4) mol/l (adrenalin). Isopernalin effects an altogether larger increase of lipolysis in the adipose tissue of the human being of old age in already smaller concentrations compared with other age groups. These findings refer to a higher affinity of adrenergic beta-receptors of the adipocytes in this age period, but also to possible age differences in the chain of lipolysis mediated by cAMP."}
{"id": "PMID:186966", "title": "[Serodiagnosis of rheumatic disorders].", "content": "For the serological diagnostics of the diseases caused by Streptococcus pyogenes (A-streptococci) and secondary diseases (rheumatic fever, acute glomerulonephritis) in the first place the anti-streptolysin reaction is at disposal. In the judgment age is to be taken into consideration and the proportion of the inhibitor in the serum is to be removed by absorption with dextran sulphate. Reliable evidence is to be expected only by the course of the titre. If possible, the antistreptolysin reaction should be supplemented by a second reaction, for which purpose the anti-desoxyribonuclease B-reaction is to be recommended. For supporting the diagnostics of the rheumatoid arthritis at least 2 reactions should be performed, i. e. a haemagglutination test (e. g. after Podliachouk-Harboe) and a particle agglutination test (latex fixation reaction). By means of them the rheumatoid factors (above all antibodies of the IgM-class against gamma-globulin) are proved. The haemagglutinations connect a high specifity with a more insignificant sensitivity, in the particle agglutinations the reverse is the case. Apart from the serological tests mentioned here other proved reactions are mentioned. Besides, data on the valuation of the results and their diagnostic importance are in this paper.", "contents": "[Serodiagnosis of rheumatic disorders]. For the serological diagnostics of the diseases caused by Streptococcus pyogenes (A-streptococci) and secondary diseases (rheumatic fever, acute glomerulonephritis) in the first place the anti-streptolysin reaction is at disposal. In the judgment age is to be taken into consideration and the proportion of the inhibitor in the serum is to be removed by absorption with dextran sulphate. Reliable evidence is to be expected only by the course of the titre. If possible, the antistreptolysin reaction should be supplemented by a second reaction, for which purpose the anti-desoxyribonuclease B-reaction is to be recommended. For supporting the diagnostics of the rheumatoid arthritis at least 2 reactions should be performed, i. e. a haemagglutination test (e. g. after Podliachouk-Harboe) and a particle agglutination test (latex fixation reaction). By means of them the rheumatoid factors (above all antibodies of the IgM-class against gamma-globulin) are proved. The haemagglutinations connect a high specifity with a more insignificant sensitivity, in the particle agglutinations the reverse is the case. Apart from the serological tests mentioned here other proved reactions are mentioned. Besides, data on the valuation of the results and their diagnostic importance are in this paper."}
{"id": "PMID:186967", "title": "[Peculiarities of the clinical picture, diagnosis and prognosis of insulinoma].", "content": "It is reported on a patient with insulinoma whose diagnosis was made 16 years ago. Operation report: Insulinoma with the histological picture of a little expressed malignant degeneration. After 6 years recidivation of the clinical picture of an insulinoma. Operation report: Metastasis of a malignant insulinoma of the size of a hazel nut. After operation the patient had no complaints and was able to work for 8 years. Repeated hypoglycaemic conditions caused a third operation: In the cauda metastasis of a malignant insulinoma. After operation 18 months symptom-free with good health. The prognosis is discussed, emphasizing the unusually long course in malignant degeneration in the case described, as it hitherto was observed for the first time. It is also referred to some peculiarities of the carbohydrate metabolism of this patient. At length the necessity of an early diagnosis and a timely surgical treatment of the insulinoma is emphasized.", "contents": "[Peculiarities of the clinical picture, diagnosis and prognosis of insulinoma]. It is reported on a patient with insulinoma whose diagnosis was made 16 years ago. Operation report: Insulinoma with the histological picture of a little expressed malignant degeneration. After 6 years recidivation of the clinical picture of an insulinoma. Operation report: Metastasis of a malignant insulinoma of the size of a hazel nut. After operation the patient had no complaints and was able to work for 8 years. Repeated hypoglycaemic conditions caused a third operation: In the cauda metastasis of a malignant insulinoma. After operation 18 months symptom-free with good health. The prognosis is discussed, emphasizing the unusually long course in malignant degeneration in the case described, as it hitherto was observed for the first time. It is also referred to some peculiarities of the carbohydrate metabolism of this patient. At length the necessity of an early diagnosis and a timely surgical treatment of the insulinoma is emphasized."}
{"id": "PMID:186968", "title": "[Serum protein changes in liver transplantation in the dog].", "content": "Hemorrhage and shock gave rise to quantitative determination of serum protein changes by means of the two-dimensional immunoelectrophoresis according to Laurell. 5 proteins showed significant changes. There were no new protein peaks or products of decomposition of other serum proteins. The liver injured by ischemia can not alone be responsible for the shift of serum proteins. Rather probably the majority of lost proteins remains in the splanchnic area.", "contents": "[Serum protein changes in liver transplantation in the dog]. Hemorrhage and shock gave rise to quantitative determination of serum protein changes by means of the two-dimensional immunoelectrophoresis according to Laurell. 5 proteins showed significant changes. There were no new protein peaks or products of decomposition of other serum proteins. The liver injured by ischemia can not alone be responsible for the shift of serum proteins. Rather probably the majority of lost proteins remains in the splanchnic area."}
{"id": "PMID:186969", "title": "Histochemical and ultrastructural alterations of the duodenum in acute hypoxia.", "content": "Laboratory animals were kept for 2, 8 and 16 hours in a pressure chamber, the air of which contained 8% O2 and 92% N2. Histochemical and ultrastructural examinations revealed the following duodenal alterations: 1. The alkaline phosphatase activity of the epithelium and glandular epithelium showed no alteration; the acid phosphatase activity was slightly increased in hypoxia. 2. The succinic dehydrogenase and cytochrome C oxidase activities of the glandular epithelium showed a marked decrease. 3. Two hours of hypoxia led to destruction of the microvillous epithelium. Prolonged hypoxia resulted in the destruction of the microvilli as well as of the cuticula. 4. Hypoxia of short duration had no damaging effect on glandular epithelial cells. After 8 to 16 hours of hypoxia, glandular secretion was reduced and the epithelial cells were evacuated. From the findings of the present investigation it is concluded that the decrease in the production of protective intestinal juice, due to the damaging effect of hypoxia on the epithelium and glandular epithelium as well as on the mitochondria, and the increase in the absorption of the intestinal content should be considered responsible of the additional damages to the intestinal epithelium.", "contents": "Histochemical and ultrastructural alterations of the duodenum in acute hypoxia. Laboratory animals were kept for 2, 8 and 16 hours in a pressure chamber, the air of which contained 8% O2 and 92% N2. Histochemical and ultrastructural examinations revealed the following duodenal alterations: 1. The alkaline phosphatase activity of the epithelium and glandular epithelium showed no alteration; the acid phosphatase activity was slightly increased in hypoxia. 2. The succinic dehydrogenase and cytochrome C oxidase activities of the glandular epithelium showed a marked decrease. 3. Two hours of hypoxia led to destruction of the microvillous epithelium. Prolonged hypoxia resulted in the destruction of the microvilli as well as of the cuticula. 4. Hypoxia of short duration had no damaging effect on glandular epithelial cells. After 8 to 16 hours of hypoxia, glandular secretion was reduced and the epithelial cells were evacuated. From the findings of the present investigation it is concluded that the decrease in the production of protective intestinal juice, due to the damaging effect of hypoxia on the epithelium and glandular epithelium as well as on the mitochondria, and the increase in the absorption of the intestinal content should be considered responsible of the additional damages to the intestinal epithelium."}
{"id": "PMID:186971", "title": "Angiographic differentiation of thoracic aneurysms and neoplasms.", "content": "The distinction between nondissecting aneuryms of the thoracic aorta and thoracic neoplasms may be difficult. The aortographic findings associated with aneurysms may be subtle. However, when the aortogram is properly performed and interpreted and the findings correlated with the plain chest roentgenograms the distinction between aneurysms and neoplasms may be made consistently. The thoracic aortogram should be filmed in at least 2 projections and abdominal aortography and ultrasonography should be performed. With aneurysms the aortographic signs include widening (often slight) of the aortic lumen, thickening of the aortic wall, small ulcer-like collections of contrast and non-filling of regional intercostal arteries. With neoplasms none of these radiological features is to be anticipated, while the aorta will be normal, displaced or narrowed.", "contents": "Angiographic differentiation of thoracic aneurysms and neoplasms. The distinction between nondissecting aneuryms of the thoracic aorta and thoracic neoplasms may be difficult. The aortographic findings associated with aneurysms may be subtle. However, when the aortogram is properly performed and interpreted and the findings correlated with the plain chest roentgenograms the distinction between aneurysms and neoplasms may be made consistently. The thoracic aortogram should be filmed in at least 2 projections and abdominal aortography and ultrasonography should be performed. With aneurysms the aortographic signs include widening (often slight) of the aortic lumen, thickening of the aortic wall, small ulcer-like collections of contrast and non-filling of regional intercostal arteries. With neoplasms none of these radiological features is to be anticipated, while the aorta will be normal, displaced or narrowed."}
{"id": "PMID:186981", "title": "[Long-term cultures of experimental CNS tumours as models in neurooncological research (author's transl)].", "content": "Experiences with the behaviour of long-term cultures of experimental CNS tumours of rats induced by methylnitosourea of ethylnitrosourea, resp., are reported. Differences in cell kinetic parameters result in a selection of the best adapted cell type among those ones existing in the primary tumour. In some long-term cultures of gliomas and neurinomas an increasing polymorphism is observed by which these lines gain the morphological appearance of a glioblastoma multiforme. The loss of cell-specific morphological differentiations is a further type of anaplastic changes. In neuroectodermal tumour strains these alterations are temporarily reversible by means of addition of dibutyryl cyclic AMP to the culture fluid. There is no relationship between the type of tumour and the degree of anaplastic changes in vitro. Some cell strains remain constant for years and retain their specific properties. Their application as tester strains in neurooncological studies is recommended.", "contents": "[Long-term cultures of experimental CNS tumours as models in neurooncological research (author's transl)]. Experiences with the behaviour of long-term cultures of experimental CNS tumours of rats induced by methylnitosourea of ethylnitrosourea, resp., are reported. Differences in cell kinetic parameters result in a selection of the best adapted cell type among those ones existing in the primary tumour. In some long-term cultures of gliomas and neurinomas an increasing polymorphism is observed by which these lines gain the morphological appearance of a glioblastoma multiforme. The loss of cell-specific morphological differentiations is a further type of anaplastic changes. In neuroectodermal tumour strains these alterations are temporarily reversible by means of addition of dibutyryl cyclic AMP to the culture fluid. There is no relationship between the type of tumour and the degree of anaplastic changes in vitro. Some cell strains remain constant for years and retain their specific properties. Their application as tester strains in neurooncological studies is recommended."}
{"id": "PMID:186977", "title": "[Mechanism of internal inhibition (role of the sympathetic nervous system in sleep phenomena)].", "content": "It has been shown on cats that the role of the sympathetic nervous system in sleep phenomena is of an adaptive nature and is effected through chain neurohormonal reactions in which adrenaline possessing a two-phase action plays a major part: it induces excitation followed by sleep. Sleep is regarded as a variety of internal inhibition, elaborated as an adaptive reaction to the changing conditions of environment, which later becomes a behavioral reaction.", "contents": "[Mechanism of internal inhibition (role of the sympathetic nervous system in sleep phenomena)]. It has been shown on cats that the role of the sympathetic nervous system in sleep phenomena is of an adaptive nature and is effected through chain neurohormonal reactions in which adrenaline possessing a two-phase action plays a major part: it induces excitation followed by sleep. Sleep is regarded as a variety of internal inhibition, elaborated as an adaptive reaction to the changing conditions of environment, which later becomes a behavioral reaction."}
{"id": "PMID:186982", "title": "[Amyotrophic lateral sclerosis with myoclonic bodies (Lafora bodies) (author's transl)].", "content": "In the present investigation 2 sporadic cases of amyotrophic lateral sclerosis with the occurrence of myoclonic bodies (Lafora bodies) in the CNS are reported. The patients died after about 14 respectively 8 months lasting disease at the age of 41 and 43, respectively under the clinical signs of an ALS. Morphology, staining qualities, and the distribution of the myoclonic bodies in our cases correspond to the adult form of the myoclonic body disease (type Lundborg). In the literature we found further 6 cases of neurogenic muscle atrophy with the occurrence of myoclonic bodies in the CNS so that one might suppose a syntropy of these two affections. The possible pathophysiological relations of neurogenic muscle atrophy to the occurrence of myoclonic body disease in adults are briefly discussed.", "contents": "[Amyotrophic lateral sclerosis with myoclonic bodies (Lafora bodies) (author's transl)]. In the present investigation 2 sporadic cases of amyotrophic lateral sclerosis with the occurrence of myoclonic bodies (Lafora bodies) in the CNS are reported. The patients died after about 14 respectively 8 months lasting disease at the age of 41 and 43, respectively under the clinical signs of an ALS. Morphology, staining qualities, and the distribution of the myoclonic bodies in our cases correspond to the adult form of the myoclonic body disease (type Lundborg). In the literature we found further 6 cases of neurogenic muscle atrophy with the occurrence of myoclonic bodies in the CNS so that one might suppose a syntropy of these two affections. The possible pathophysiological relations of neurogenic muscle atrophy to the occurrence of myoclonic body disease in adults are briefly discussed."}
{"id": "PMID:186979", "title": "[Experiments with simultaneous immunization against cytomegalovirus infection and rubella].", "content": "An immunisation trial with simultaneously applicated attenuated rubellavirus (Cendehill) and attenuated cytomegalovirus (TOWNE 125) was done in adults. There was no difference in antibody-titers against both viruses and in side-reactions (local ones only) between simultaneous or single application of the two viruses. Adults immunized against cytomegalovirus two years ago still had IF-IgG-antibodies; in only 1 of 8 volunteers there was a significant antibody-decline.", "contents": "[Experiments with simultaneous immunization against cytomegalovirus infection and rubella]. An immunisation trial with simultaneously applicated attenuated rubellavirus (Cendehill) and attenuated cytomegalovirus (TOWNE 125) was done in adults. There was no difference in antibody-titers against both viruses and in side-reactions (local ones only) between simultaneous or single application of the two viruses. Adults immunized against cytomegalovirus two years ago still had IF-IgG-antibodies; in only 1 of 8 volunteers there was a significant antibody-decline."}
{"id": "PMID:186983", "title": "[The effect produced by fine-dust extracts on cells in vitro, with particular regard to cancerogenic components (author's transl)].", "content": "Airborne dust is toxic for cells cultured in vitro and able to transform these cells to cancerous. The effect of extracts from atmospheric dust has been investigated. The dust samples were extracted by means of DMSO alone or in combination acetone-DMSO. Dosage of the extract was done according to its benzo(a)pyrene content (mug/ml medium). Dust extract with a concentration of 1 mug benzo(a)pyrene/ml exerted a toxic effect upon mouse macrophages (cell line IC-21) and human lymphocytes after stimulation. The degree of toxicity was estimated from the percentage of damaged cells seen in the dye exclusion test and from the amount of lactate dehydrogenase and lactate released into the medium in the case of macrophages. In the case of lymphocytes the degree of toxicity was estimated from the extent of inhibition of DNA synthesis. In the carcinogenicity test, hamster kidney cells were first treated with the extract and then incubated with Simian Virus (SV-)40. Treatment of the cell cultures with extract from airborne dust in a concentration of 0.01 and 0.1 mug benzo(a)pyrene/ml clearly enhances the rate of transformation caused by SV 40.", "contents": "[The effect produced by fine-dust extracts on cells in vitro, with particular regard to cancerogenic components (author's transl)]. Airborne dust is toxic for cells cultured in vitro and able to transform these cells to cancerous. The effect of extracts from atmospheric dust has been investigated. The dust samples were extracted by means of DMSO alone or in combination acetone-DMSO. Dosage of the extract was done according to its benzo(a)pyrene content (mug/ml medium). Dust extract with a concentration of 1 mug benzo(a)pyrene/ml exerted a toxic effect upon mouse macrophages (cell line IC-21) and human lymphocytes after stimulation. The degree of toxicity was estimated from the percentage of damaged cells seen in the dye exclusion test and from the amount of lactate dehydrogenase and lactate released into the medium in the case of macrophages. In the case of lymphocytes the degree of toxicity was estimated from the extent of inhibition of DNA synthesis. In the carcinogenicity test, hamster kidney cells were first treated with the extract and then incubated with Simian Virus (SV-)40. Treatment of the cell cultures with extract from airborne dust in a concentration of 0.01 and 0.1 mug benzo(a)pyrene/ml clearly enhances the rate of transformation caused by SV 40."}
{"id": "PMID:186978", "title": "[Infections transmitted in swimming pools].", "content": "Public swimmingpools can be the source of infections due to micro-organism such as mycobacterium balnei, adeno and enteroviruses, the virus of plantar warts and molluscum contagiosum, the TRIC-Agent of swimmingpool-conjonctivitis and pathogenic fungi. The transmission of trichomonas vaginalis is considered unlikely-Water of pools, supposed to present satisfactory qualities by standard controls, was found to contain pathogenic staphylococci and pseudomonas aeruginosa. Effective preventive measures include the continuous recording of the redox-potential of the water, limiting the number of visitors to pool design specifications, better desinfection of sanitary installations, regular maintenance of technical equipment including frequent backwashing of filters and exclusion of visitors with communicable disease.", "contents": "[Infections transmitted in swimming pools]. Public swimmingpools can be the source of infections due to micro-organism such as mycobacterium balnei, adeno and enteroviruses, the virus of plantar warts and molluscum contagiosum, the TRIC-Agent of swimmingpool-conjonctivitis and pathogenic fungi. The transmission of trichomonas vaginalis is considered unlikely-Water of pools, supposed to present satisfactory qualities by standard controls, was found to contain pathogenic staphylococci and pseudomonas aeruginosa. Effective preventive measures include the continuous recording of the redox-potential of the water, limiting the number of visitors to pool design specifications, better desinfection of sanitary installations, regular maintenance of technical equipment including frequent backwashing of filters and exclusion of visitors with communicable disease."}
{"id": "PMID:186984", "title": "[Increased blood-CO-content in humans and animals by incorporated halogenated hydrocarbons (author's transl)].", "content": "Contrarily to the general opinion about the harmlessness of dichloromethane, clear functional disturbances of the central nervous system could be recorded by means of effect investigations as well in humans as in animals. The depressive effect on the REM-sleep of albino rats was especially well recognisable, similarly as with carbon monoxide exposure. Surprisingly the analytical investigations of the blood of these animals showed a clearly elevated blood-CO-content after exposure to dichloromethane. Further experiments during which albino rats were exposed three hours along to a dichloromethane-concentration equal to the TLV (1750 mg/m3!!) resulted in a blood-COHb-level of about 13%, corresponding to over 30 mug CO/ml blood. So high blood-COHb-levels are obtained after a three-hour-exposure to 120 ppm CO. Following these findings, a number of halogenated and oxygenated hydrocarbon compounds of the methane and ethane series were investigated relatively to their CO-forming capacity. Only the di- and trihalogenated methane derivatives were found leading to an increased blood-COHb-level. After a three hours-exposure to 1000 ppm respectively the jodoalkanes yielding about 23% COHb were strongestly, the bromoalkanes with about 20% COHb more strongly and the chloroalkanes with about 12% COHb strongly implicated in the endogenous CO-formation. By means of detailed experiments with human volunteers (non-smokers) it resulted that after eight-hours-exposure to 500 ppm dichloromethane (TLV) a mean value for CO-content in blood of about 30 mug/ml corresponding to 12% COHb was obtained, in one case raising as high as 60 mug CO/1 ml blood or 24% COHb. After an eight-hours-exposure to 100 ppm of the halocarbon, the blood-COHb-level reached 5%. The elimination was very slow, so that 24 to 26 hours were necessary to reestablish the original blood-COHb-level. These results show that the actually TLV for dichloromethane e.g. 1750 mg/m3 has to be revised, because a fifth of this value already leads to a blood-COHb-content equal to that produced by the TLV for carbon monoxide and that also eventually arising problems due to gas mixtures have to be considered and thoroughly investigated.", "contents": "[Increased blood-CO-content in humans and animals by incorporated halogenated hydrocarbons (author's transl)]. Contrarily to the general opinion about the harmlessness of dichloromethane, clear functional disturbances of the central nervous system could be recorded by means of effect investigations as well in humans as in animals. The depressive effect on the REM-sleep of albino rats was especially well recognisable, similarly as with carbon monoxide exposure. Surprisingly the analytical investigations of the blood of these animals showed a clearly elevated blood-CO-content after exposure to dichloromethane. Further experiments during which albino rats were exposed three hours along to a dichloromethane-concentration equal to the TLV (1750 mg/m3!!) resulted in a blood-COHb-level of about 13%, corresponding to over 30 mug CO/ml blood. So high blood-COHb-levels are obtained after a three-hour-exposure to 120 ppm CO. Following these findings, a number of halogenated and oxygenated hydrocarbon compounds of the methane and ethane series were investigated relatively to their CO-forming capacity. Only the di- and trihalogenated methane derivatives were found leading to an increased blood-COHb-level. After a three hours-exposure to 1000 ppm respectively the jodoalkanes yielding about 23% COHb were strongestly, the bromoalkanes with about 20% COHb more strongly and the chloroalkanes with about 12% COHb strongly implicated in the endogenous CO-formation. By means of detailed experiments with human volunteers (non-smokers) it resulted that after eight-hours-exposure to 500 ppm dichloromethane (TLV) a mean value for CO-content in blood of about 30 mug/ml corresponding to 12% COHb was obtained, in one case raising as high as 60 mug CO/1 ml blood or 24% COHb. After an eight-hours-exposure to 100 ppm of the halocarbon, the blood-COHb-level reached 5%. The elimination was very slow, so that 24 to 26 hours were necessary to reestablish the original blood-COHb-level. These results show that the actually TLV for dichloromethane e.g. 1750 mg/m3 has to be revised, because a fifth of this value already leads to a blood-COHb-content equal to that produced by the TLV for carbon monoxide and that also eventually arising problems due to gas mixtures have to be considered and thoroughly investigated."}
{"id": "PMID:186989", "title": "[Encephalitis (predilectiveness and \"slow\" infections)].", "content": "Chronic progressive forms of encephalitis (epidemic Economo, tick-borne) are considered from the concept of \"slow infections\" where the virus following the acute phase of the disease, in the latent state during many years, is persistent in the human organism. The author attributes herpetic encephalitis to this group of disorders. Unlike the slow, gradually developing forms of encephalitis and diseases with a protracted incubational period, herpetical encephalitis develops acutely and may be allocated to \"slow infections\" in respect to a protracted infection with a long-term persistent virus in the latent condition.", "contents": "[Encephalitis (predilectiveness and \"slow\" infections)]. Chronic progressive forms of encephalitis (epidemic Economo, tick-borne) are considered from the concept of \"slow infections\" where the virus following the acute phase of the disease, in the latent state during many years, is persistent in the human organism. The author attributes herpetic encephalitis to this group of disorders. Unlike the slow, gradually developing forms of encephalitis and diseases with a protracted incubational period, herpetical encephalitis develops acutely and may be allocated to \"slow infections\" in respect to a protracted infection with a long-term persistent virus in the latent condition."}
{"id": "PMID:186990", "title": "Cross-resistance of transformed mouse cells to some drugs.", "content": "The Colcemid-resistant L--53 cell strain was examined for cross-resistance to metaphase inhibotors (Vincristine, Vinblastine, estradiol-17beta), an antitumor antibiotic (Rubomycin C) and an alkylating agent (Lycurim), compared with the Colcemid-sensitive L cells. The L-53 cells proved to be resistant besides colchicine to Vincristine, Vinblastine and estradiol-17beta concerning their antimitotic effect. The comparison of the viability of L and L-53 cells in the presence of Rubomycin C and Lycurim showed a resistance of the L-53 cells to Rubomycin C, while the effect of Lycurim was the same on both cell lines. The chromosome-mutagenic action of Lycurim was also equal on both cell lines.", "contents": "Cross-resistance of transformed mouse cells to some drugs. The Colcemid-resistant L--53 cell strain was examined for cross-resistance to metaphase inhibotors (Vincristine, Vinblastine, estradiol-17beta), an antitumor antibiotic (Rubomycin C) and an alkylating agent (Lycurim), compared with the Colcemid-sensitive L cells. The L-53 cells proved to be resistant besides colchicine to Vincristine, Vinblastine and estradiol-17beta concerning their antimitotic effect. The comparison of the viability of L and L-53 cells in the presence of Rubomycin C and Lycurim showed a resistance of the L-53 cells to Rubomycin C, while the effect of Lycurim was the same on both cell lines. The chromosome-mutagenic action of Lycurim was also equal on both cell lines."}
{"id": "PMID:186991", "title": "Glycerolkinase--a regulatory enzyme of gluconeogenesis?", "content": "1. The development of glycerolkinase before and after birth was investigated in liver and kidney of rat and hamster. In rat liver, enzyme activity increased very slowly before birth and rapidly thereafter, reaching adult values at the 6th day of postnatal life. In hamster liver, glycerolkinase was considerably elevated already in utero, increased dramatically within the 1st day of postnatal life and reached adult values at the end of the 1st week. The development of hepatic glycerolkinase was compared with that of hepatic phosphoenolpyruvate carboxykinase of rat and hamster up to the 20th day of postnatal life. The different time-courses of the levels of these two enzymes before and after birth as well as the known kinetics of serum insulin, glucagon and corticosterone during that time suggested that none of these hormones is involved in the perinatal development of hepatic glycerolkinase activity. In contrast to liver, kidney glycerolkinase activity in both, rat and hamster, showed a delayed increase during the first week of postnatal life followed by a more pronounced elevation to adult values within the following 2 weeks. 2. When liver and kidney glycerolkinase activity was investigated during starvation (+/- refeeding), in alloxan diabetes(+/- insulin) and after adrenalectomy (+/- cortisol) no significant change in enzyme activity per g tissue could be detected either in liver or in kidney. However, total hepatic glycerolkinase activity was diminished during starvation as a consequence of decreasing liver weight. 3. Incorporation of U-[14C]-glycerol into CO2, lipids and glucose + glycogen by rat liver and kidney cortex slices was studied under the above gluconeogenetic conditions. Despite unchanged glycerolkinase activity in both organs, gluconeogenesis from glycerol was enhanced during starvation and in chronic alloxan diabetes, and could be reversed by refeeding and insulin replacement, respectively. 4. Feeding 20% of linolic acid to normal, alloxan-diabetic or adrenalectomized rats resulted in a significant increase in glycerolkinase activity in liver but not in kidney. 5. From the present findings it is suggested that the first step of gluconeogenesis from glycerol in liver and kidney is not influenced by glucagon, insulin and glucocorticoids, which are generally believed to regulate the rate of gluconeogenesis from non-glycerol precursors, but probably by the change in blood glycerol concentration.", "contents": "Glycerolkinase--a regulatory enzyme of gluconeogenesis? 1. The development of glycerolkinase before and after birth was investigated in liver and kidney of rat and hamster. In rat liver, enzyme activity increased very slowly before birth and rapidly thereafter, reaching adult values at the 6th day of postnatal life. In hamster liver, glycerolkinase was considerably elevated already in utero, increased dramatically within the 1st day of postnatal life and reached adult values at the end of the 1st week. The development of hepatic glycerolkinase was compared with that of hepatic phosphoenolpyruvate carboxykinase of rat and hamster up to the 20th day of postnatal life. The different time-courses of the levels of these two enzymes before and after birth as well as the known kinetics of serum insulin, glucagon and corticosterone during that time suggested that none of these hormones is involved in the perinatal development of hepatic glycerolkinase activity. In contrast to liver, kidney glycerolkinase activity in both, rat and hamster, showed a delayed increase during the first week of postnatal life followed by a more pronounced elevation to adult values within the following 2 weeks. 2. When liver and kidney glycerolkinase activity was investigated during starvation (+/- refeeding), in alloxan diabetes(+/- insulin) and after adrenalectomy (+/- cortisol) no significant change in enzyme activity per g tissue could be detected either in liver or in kidney. However, total hepatic glycerolkinase activity was diminished during starvation as a consequence of decreasing liver weight. 3. Incorporation of U-[14C]-glycerol into CO2, lipids and glucose + glycogen by rat liver and kidney cortex slices was studied under the above gluconeogenetic conditions. Despite unchanged glycerolkinase activity in both organs, gluconeogenesis from glycerol was enhanced during starvation and in chronic alloxan diabetes, and could be reversed by refeeding and insulin replacement, respectively. 4. Feeding 20% of linolic acid to normal, alloxan-diabetic or adrenalectomized rats resulted in a significant increase in glycerolkinase activity in liver but not in kidney. 5. From the present findings it is suggested that the first step of gluconeogenesis from glycerol in liver and kidney is not influenced by glucagon, insulin and glucocorticoids, which are generally believed to regulate the rate of gluconeogenesis from non-glycerol precursors, but probably by the change in blood glycerol concentration."}
{"id": "PMID:186992", "title": "[Inhibition of the cyclic AMP splitting myocardial nucleotide gydrolase by 5-methyl-7-diethylamino-s-triazol-(1,5-alpha)pyrimidine (rocornal)].", "content": "5-Methyl-7-diethylamino-s-triazolo-(1,5-alpha)pyrimidine (Rocornal, trapidil), which has been introduced in clinical medicine as a coronary vasodilatator, competitively inhibits the cyclic AMP splitting nucleotidehydrolase (phosphodiesterase) from the heart muscle. The K1 value for Rocornal is 0.14 +/- 0.016 mM. The enzyme inhibition by this compound is abolished after an exchange of the diethylamino-group in C-7 position against dimethylamine and chloride. The proved triazolo-pyrimidines were without effect on myocardial adenylate cyclase activity. It is concluded that the vasodilatory effect of Rocornal may be realized in smooth muscle cells by an inhibition of cyclic AMP breakdown.", "contents": "[Inhibition of the cyclic AMP splitting myocardial nucleotide gydrolase by 5-methyl-7-diethylamino-s-triazol-(1,5-alpha)pyrimidine (rocornal)]. 5-Methyl-7-diethylamino-s-triazolo-(1,5-alpha)pyrimidine (Rocornal, trapidil), which has been introduced in clinical medicine as a coronary vasodilatator, competitively inhibits the cyclic AMP splitting nucleotidehydrolase (phosphodiesterase) from the heart muscle. The K1 value for Rocornal is 0.14 +/- 0.016 mM. The enzyme inhibition by this compound is abolished after an exchange of the diethylamino-group in C-7 position against dimethylamine and chloride. The proved triazolo-pyrimidines were without effect on myocardial adenylate cyclase activity. It is concluded that the vasodilatory effect of Rocornal may be realized in smooth muscle cells by an inhibition of cyclic AMP breakdown."}
{"id": "PMID:186993", "title": "Mammary tumour virus (MTV)-specific immune complex deposites in renal glomeruli of MTV-infected tumour-free mice.", "content": "Using direct and indirect immunofluorescence tests MTV-specific immune complex deposits were found in tumour-free female mice of the strains C3H/Bln, CBA/Bln, XVII/BlnfCBA/Bln, and CBA/BlnfXVII/Bln. These deposits consist of immunoglobulin, complement, and MTV antigen(s). The immune complex deposition increases with age. Antibodies eluted from renal tissue homogenate react with both MTV-A and -B particles in immunofluorescence tests performed on mouse mammary tumour slices. By these results the earlier finding of age-dependent spontaneously occurring anti MTV antibodies in naturally MTV-infected mice is confirmed and completed.", "contents": "Mammary tumour virus (MTV)-specific immune complex deposites in renal glomeruli of MTV-infected tumour-free mice. Using direct and indirect immunofluorescence tests MTV-specific immune complex deposits were found in tumour-free female mice of the strains C3H/Bln, CBA/Bln, XVII/BlnfCBA/Bln, and CBA/BlnfXVII/Bln. These deposits consist of immunoglobulin, complement, and MTV antigen(s). The immune complex deposition increases with age. Antibodies eluted from renal tissue homogenate react with both MTV-A and -B particles in immunofluorescence tests performed on mouse mammary tumour slices. By these results the earlier finding of age-dependent spontaneously occurring anti MTV antibodies in naturally MTV-infected mice is confirmed and completed."}
{"id": "PMID:186995", "title": "Pseudomonas cytochrome c peroxidase. XII. Product inhibition studies.", "content": "Kinetic studies of the reaction mechanism of Pseudomonas cytochrome c peroxidase (PaCCP) were made by the method of product inhibition using oxidized cytochrome C (551 P.aeruginosa) and oxidized Pseudomonas azurin as products. Inhibition by the two oxidized substrates was linearly non-competitive towards the respective reduced electron donor and towards hydrogen peroxide. Although a full kinetic analysis is experimentally impossible in a peroxidase-type reaction, the results do provide some evidence in favour of an ordered reaction mechanism in which hydrogen peroxide is the first to add to PaCCP and electron donor the second.", "contents": "Pseudomonas cytochrome c peroxidase. XII. Product inhibition studies. Kinetic studies of the reaction mechanism of Pseudomonas cytochrome c peroxidase (PaCCP) were made by the method of product inhibition using oxidized cytochrome C (551 P.aeruginosa) and oxidized Pseudomonas azurin as products. Inhibition by the two oxidized substrates was linearly non-competitive towards the respective reduced electron donor and towards hydrogen peroxide. Although a full kinetic analysis is experimentally impossible in a peroxidase-type reaction, the results do provide some evidence in favour of an ordered reaction mechanism in which hydrogen peroxide is the first to add to PaCCP and electron donor the second."}
{"id": "PMID:186998", "title": "Corticosterone, 18-OH-deoxycorticosterone, deoxycorticosterone and aldosterone secretion in tissue culture of foetal rat adrenals in the presence and the absence of ACTH.", "content": "A method for simultaneous analysis of the main corticosteroids secreted by the rat adrenal is described. Purification is performed using previously established steps involving dichloromethane extraction, ethanol-cyclo-hexane partition and Sephadex-LH-20 column chromatography. Deoxycorticosterone and aldosterone are then quantitated with radioimmunoassay and corticosterone and 18-hydroxy-deoxycorticosterone with gas liquid chromatography as their 0-methyloxime=trimethylsilyl ethers. The coefficient of variation of the method for these steroids in concentrations found in the tissue culture of feotal rat adrenals varies between 3.9-10.9 %. The secretion of these steroids in the tissue culture of foetal rat adrenals is studied. The steroid secretory pattern is correlated with a differentiation stage of the cultures as detected by electron microscopy. The initial secretory activity declines considerably after 15 days of cultivation to a low level. This is the case also with respect to aldosterone although the cortical cell population changed from the mixed population of the differentiated (zona fasciculata-like) and undifferentiated (zona glomerulosa-like) cells to homogenous undifferentiated growth. Addition of ACTH increased deoxycorticosterone secretion rapidly. Corticosterone, 18-hydroxy-deoxycorticosterone and aldosterone secretion was observed only after the differentiation of the cells (especially changes in their mitochondrial compartment) was evident morphologically.", "contents": "Corticosterone, 18-OH-deoxycorticosterone, deoxycorticosterone and aldosterone secretion in tissue culture of foetal rat adrenals in the presence and the absence of ACTH. A method for simultaneous analysis of the main corticosteroids secreted by the rat adrenal is described. Purification is performed using previously established steps involving dichloromethane extraction, ethanol-cyclo-hexane partition and Sephadex-LH-20 column chromatography. Deoxycorticosterone and aldosterone are then quantitated with radioimmunoassay and corticosterone and 18-hydroxy-deoxycorticosterone with gas liquid chromatography as their 0-methyloxime=trimethylsilyl ethers. The coefficient of variation of the method for these steroids in concentrations found in the tissue culture of feotal rat adrenals varies between 3.9-10.9 %. The secretion of these steroids in the tissue culture of foetal rat adrenals is studied. The steroid secretory pattern is correlated with a differentiation stage of the cultures as detected by electron microscopy. The initial secretory activity declines considerably after 15 days of cultivation to a low level. This is the case also with respect to aldosterone although the cortical cell population changed from the mixed population of the differentiated (zona fasciculata-like) and undifferentiated (zona glomerulosa-like) cells to homogenous undifferentiated growth. Addition of ACTH increased deoxycorticosterone secretion rapidly. Corticosterone, 18-hydroxy-deoxycorticosterone and aldosterone secretion was observed only after the differentiation of the cells (especially changes in their mitochondrial compartment) was evident morphologically."}
{"id": "PMID:186999", "title": "Immunoreactive ACTH, immunoreactive human chorionic somatomammotrophin (HCS) and 11-OH steroids plasma levels in normal and pathological pregnancies.", "content": "Plasma immunoreactive ACTH (I.R.ACTH), immunoreactive human chorionic somatomammotrophin (I.R.HCS) and 11-OH steroids levels were measured during normal and pathological pregnancies. Plasma I.R.ACTH levels were found to be above normal during pregnancy, with a slight decrease near term. This observation correlates well with the recent description of human chorionic corticotrophin (HCC), i.e. a factor of placental origin possessing a high biological adrenocorticotrophic activity and presenting partial immunological cross-reaction with human ACTH. The 11-OH steroids levels, as measured by a fluorimetric method, increased regularly during pregnancy but, unlike ACTH, reached their highest value near term, I.R.HCS increased progressively until term when a slight decrease was observed. In pathological pregnancies, I.R.ACTH levels behaved like other placental hormones. On the contrary, 11-OH steroids levels remained generally unmodified. Treatment with high doses of prednisolone caused no inhibition of the plasma I.R.ACTH and of plasma 11-OH steroids levels. These data suggest placental autonomy of the secretion of HCC and low adrenal responsiveness to endogenous ACTH variations throughout pregnancy.", "contents": "Immunoreactive ACTH, immunoreactive human chorionic somatomammotrophin (HCS) and 11-OH steroids plasma levels in normal and pathological pregnancies. Plasma immunoreactive ACTH (I.R.ACTH), immunoreactive human chorionic somatomammotrophin (I.R.HCS) and 11-OH steroids levels were measured during normal and pathological pregnancies. Plasma I.R.ACTH levels were found to be above normal during pregnancy, with a slight decrease near term. This observation correlates well with the recent description of human chorionic corticotrophin (HCC), i.e. a factor of placental origin possessing a high biological adrenocorticotrophic activity and presenting partial immunological cross-reaction with human ACTH. The 11-OH steroids levels, as measured by a fluorimetric method, increased regularly during pregnancy but, unlike ACTH, reached their highest value near term, I.R.HCS increased progressively until term when a slight decrease was observed. In pathological pregnancies, I.R.ACTH levels behaved like other placental hormones. On the contrary, 11-OH steroids levels remained generally unmodified. Treatment with high doses of prednisolone caused no inhibition of the plasma I.R.ACTH and of plasma 11-OH steroids levels. These data suggest placental autonomy of the secretion of HCC and low adrenal responsiveness to endogenous ACTH variations throughout pregnancy."}
{"id": "PMID:186996", "title": "Diagnosis of bronchogenic carcinoma through the cytologic examination of sputum, with special reference to tumor typing.", "content": "The results obtained in the cytologic study of sputa from 630 patients are presented. There were 251 cases of bronchogenic carcinoma; diagnosis through sputum examination was possible in 57.4 per cent of the patients. Abnormal cells were detected in an additional 24.3 per cent. Sputum examination has proven to be a valuable complement by establishing the correct diagnosis when other methods failed. Cancer cells were unequivocally identified in 45.8 per cent of the cases with normal bronchoscopic examination and in 52.4 per cent of the cases in which bronchial biopsy did not include malignant tissue. The same proportion of cases with the various tumor types was obtained by cytologic and by histologic study. However, one of the methods often showed a higher degree of cellular differentiation than the other. The number of cases with undifferentiated cancer or unclassified tumors was markedly reduced when the information concerning cell differentiation available through both methods was used. In this manner, excluding the oat cell carcinomas, only 7.6 per cent of the cases of bronchogenic carcinoma did not show any cellular differentiation. The authors recommend wider use of the information provided by simultaneous evaluation of both cytologic smears and tissue sections in order to achieve a more accurate appraisal of tumor type.", "contents": "Diagnosis of bronchogenic carcinoma through the cytologic examination of sputum, with special reference to tumor typing. The results obtained in the cytologic study of sputa from 630 patients are presented. There were 251 cases of bronchogenic carcinoma; diagnosis through sputum examination was possible in 57.4 per cent of the patients. Abnormal cells were detected in an additional 24.3 per cent. Sputum examination has proven to be a valuable complement by establishing the correct diagnosis when other methods failed. Cancer cells were unequivocally identified in 45.8 per cent of the cases with normal bronchoscopic examination and in 52.4 per cent of the cases in which bronchial biopsy did not include malignant tissue. The same proportion of cases with the various tumor types was obtained by cytologic and by histologic study. However, one of the methods often showed a higher degree of cellular differentiation than the other. The number of cases with undifferentiated cancer or unclassified tumors was markedly reduced when the information concerning cell differentiation available through both methods was used. In this manner, excluding the oat cell carcinomas, only 7.6 per cent of the cases of bronchogenic carcinoma did not show any cellular differentiation. The authors recommend wider use of the information provided by simultaneous evaluation of both cytologic smears and tissue sections in order to achieve a more accurate appraisal of tumor type."}
{"id": "PMID:187000", "title": "Localization of certain phosphatases in the male sex accessory glands of Suncus murinus sindensis, Anderson, the common shrew.", "content": "Histochemical localization of various phosphatases, alkaline phosphatase, acid phosphatase, adenosine-tri-phosphatase and glucose-6-phosphatase, have been carried out in the male sex accessory glands of Suncus murinus sindensis, ANDERSON. The seminal vesicle and the COWPER'S gland in Suncus display strong phosphatases activities in the epithelium, except the alkaline phosphatase in the in the COWPER'S gland which is more pronounced in the stroma. The possible role of these phosphatases in the secretory activities of the organ where they are localized have been discussed. In the prostate gland, no phosphatase activity could be revealed in the epithelium and the secretions.", "contents": "Localization of certain phosphatases in the male sex accessory glands of Suncus murinus sindensis, Anderson, the common shrew. Histochemical localization of various phosphatases, alkaline phosphatase, acid phosphatase, adenosine-tri-phosphatase and glucose-6-phosphatase, have been carried out in the male sex accessory glands of Suncus murinus sindensis, ANDERSON. The seminal vesicle and the COWPER'S gland in Suncus display strong phosphatases activities in the epithelium, except the alkaline phosphatase in the in the COWPER'S gland which is more pronounced in the stroma. The possible role of these phosphatases in the secretory activities of the organ where they are localized have been discussed. In the prostate gland, no phosphatase activity could be revealed in the epithelium and the secretions."}
{"id": "PMID:187001", "title": "Serum human placental lactogen (HPL) levels in patients with intact hydatidiform mole.", "content": "Serum human placental lactogen (HPL) levels in forty cases of intact hydatidiform mole were measured by radioimmunoassay. The HPL values were generally lower than normal pregnancies of the corresponding period of gestation. However, normal and occasionally higher than normal values were observed in a few cases. Serum HPL level alone is of some clinical use in the diagnosis of hydatidiform mole. When combined with human chorionic gonadotropin (HCG), a low HPL/HCG ratio for the corresponding period of amenorrhoea is a useful index in the diagnosis of hydatidiform mole.", "contents": "Serum human placental lactogen (HPL) levels in patients with intact hydatidiform mole. Serum human placental lactogen (HPL) levels in forty cases of intact hydatidiform mole were measured by radioimmunoassay. The HPL values were generally lower than normal pregnancies of the corresponding period of gestation. However, normal and occasionally higher than normal values were observed in a few cases. Serum HPL level alone is of some clinical use in the diagnosis of hydatidiform mole. When combined with human chorionic gonadotropin (HCG), a low HPL/HCG ratio for the corresponding period of amenorrhoea is a useful index in the diagnosis of hydatidiform mole."}
{"id": "PMID:186997", "title": "Cerebrospinal fluid cytology: diagnostic accuracy and comparison of different techniques.", "content": "Cytologic examination of cerebrospinal fluid was performed in 1,021 patients, using Nuclepore and Millipore filter techniques. Positive findings were obtained in 89 cases, including 40 with primary central nervous system tumors, 24 with metastatic tumors and 25 with leukemic or lymphomatous involvement. When correlated with histologic findings, the overall detection rate was 32.2 per cent for primary tumors, 53.3 per cent for metastatic tumors and 65.8 per cent for leukemia and lymphoma. Highest degree of accuracy in the primary tumor group was achieved with medulloblastoma (61.9 per cent). Among metastatic tumors, those originating in the lung (70 per cent) and breast (83 per cent) were the one most often detected. Comparison of the two filter techniques indicated a slightly higher detection rate when the Millipore filter was used. The reasons for this are not entirely clear, but increased cellular yield with the Millipore filter may be an important factor. The cytocentrifuge method was found to be generally inferior to either of the filter techniques in quality of cell preservation. Our findings indicate that diagnostic usefulness of cerebrospinal cytology depends on collection and preparation methods as well as the anatomic distribution and biologic behavior of the lesions.", "contents": "Cerebrospinal fluid cytology: diagnostic accuracy and comparison of different techniques. Cytologic examination of cerebrospinal fluid was performed in 1,021 patients, using Nuclepore and Millipore filter techniques. Positive findings were obtained in 89 cases, including 40 with primary central nervous system tumors, 24 with metastatic tumors and 25 with leukemic or lymphomatous involvement. When correlated with histologic findings, the overall detection rate was 32.2 per cent for primary tumors, 53.3 per cent for metastatic tumors and 65.8 per cent for leukemia and lymphoma. Highest degree of accuracy in the primary tumor group was achieved with medulloblastoma (61.9 per cent). Among metastatic tumors, those originating in the lung (70 per cent) and breast (83 per cent) were the one most often detected. Comparison of the two filter techniques indicated a slightly higher detection rate when the Millipore filter was used. The reasons for this are not entirely clear, but increased cellular yield with the Millipore filter may be an important factor. The cytocentrifuge method was found to be generally inferior to either of the filter techniques in quality of cell preservation. Our findings indicate that diagnostic usefulness of cerebrospinal cytology depends on collection and preparation methods as well as the anatomic distribution and biologic behavior of the lesions."}
{"id": "PMID:187003", "title": "Defective neutrophil motility in hypovitaminosis D rickets.", "content": "The chemotactic activity and random motility of neutrophils, was studied in 38 patients with hypovitaminosis D rickets, and compared with 29 healthy controls of matched age. The chemotactic activity derived from the activated rickets serum as well as the amounts of the complement components C4, C3 and C5 was normal, but the cell motility was clearly defective (p less than 0.001). A possible relationship between defective neutrophil movement and the recurrent infections seen in these patients is suggested. The possible mechanisms responsible for the defect could be the alteration in Ca/P metabolism or a defective action of the vitamin D on the neutrophils.", "contents": "Defective neutrophil motility in hypovitaminosis D rickets. The chemotactic activity and random motility of neutrophils, was studied in 38 patients with hypovitaminosis D rickets, and compared with 29 healthy controls of matched age. The chemotactic activity derived from the activated rickets serum as well as the amounts of the complement components C4, C3 and C5 was normal, but the cell motility was clearly defective (p less than 0.001). A possible relationship between defective neutrophil movement and the recurrent infections seen in these patients is suggested. The possible mechanisms responsible for the defect could be the alteration in Ca/P metabolism or a defective action of the vitamin D on the neutrophils."}
{"id": "PMID:187004", "title": "Basal and hormone-induced urinary cyclic AMP in children with renal disorders.", "content": "The excretion of cyclic AMP in urine has been examined in normal children and in children with nephrogenic diabetes insipidus or moderate renal failure (predominantly defective concentrating ability) under basal conditions and in response to antidiuretic hormone (ADH) and parathyroid hormone (PTH). In contrast to other reported data, we could not confirm an ADH- and (PTH-unresponsiveness in hereditary, congenital nephrogenic diabetes insipidus, but our patients with structural renal disorders characterized by a defective urine concentrating ability did have reduced hormonal responses. It seems necessary to define nephrogenic diabetes insipidus very carefully, and until more data are collected, there appears to be no value in the measurement of urinary cyclic AMP level in the individual patient in the differential diagnosis of disorders due to renal concentrating defects.", "contents": "Basal and hormone-induced urinary cyclic AMP in children with renal disorders. The excretion of cyclic AMP in urine has been examined in normal children and in children with nephrogenic diabetes insipidus or moderate renal failure (predominantly defective concentrating ability) under basal conditions and in response to antidiuretic hormone (ADH) and parathyroid hormone (PTH). In contrast to other reported data, we could not confirm an ADH- and (PTH-unresponsiveness in hereditary, congenital nephrogenic diabetes insipidus, but our patients with structural renal disorders characterized by a defective urine concentrating ability did have reduced hormonal responses. It seems necessary to define nephrogenic diabetes insipidus very carefully, and until more data are collected, there appears to be no value in the measurement of urinary cyclic AMP level in the individual patient in the differential diagnosis of disorders due to renal concentrating defects."}
{"id": "PMID:187005", "title": "Triglyceride storage disease. A report of two affected children associated with neurological abnormalities.", "content": "Two children are described with congenital abnormalities (microcephaly, nystagmus, deafness, hepatomegaly) and the anomalous feature of triglyceride deposits in peripheral adipose tissue associated with severe malnutrition. Peripheral adipose tissue of one of these children displayed: (a) reduced sensitivity of adenyl cyclase to stimulation by noradrenaline (b) no response in tissue levels of cyclic AMP when stimulated by isoprenaline and (c) impaired release of glycerol following stimulation with isoprenaline. The other child, with similar clinical features, showed abnormal deposits of glycogen in the liver. It is postulated that a primary metabolic defect occurs in peripheral adipose tissue (and possibly at other sites such as the liver) that interferes with triglyceride (and glycogen) mobilization during prolonged malnutrition.", "contents": "Triglyceride storage disease. A report of two affected children associated with neurological abnormalities. Two children are described with congenital abnormalities (microcephaly, nystagmus, deafness, hepatomegaly) and the anomalous feature of triglyceride deposits in peripheral adipose tissue associated with severe malnutrition. Peripheral adipose tissue of one of these children displayed: (a) reduced sensitivity of adenyl cyclase to stimulation by noradrenaline (b) no response in tissue levels of cyclic AMP when stimulated by isoprenaline and (c) impaired release of glycerol following stimulation with isoprenaline. The other child, with similar clinical features, showed abnormal deposits of glycogen in the liver. It is postulated that a primary metabolic defect occurs in peripheral adipose tissue (and possibly at other sites such as the liver) that interferes with triglyceride (and glycogen) mobilization during prolonged malnutrition."}
{"id": "PMID:187006", "title": "Histological typing of lung cancer. Application of the World Health Organization classification to 479 cases.", "content": "Four hundred and seventy nine primary lung cancers were typed according to the WHO histological classification. The character of the material and the methods of investigation are described. All patients had been subjected to mediastinoscopy and 313 patients had been operated upon. Nearly half of the tumours (48 per cent) was epidermoid carcinomas. Small cell anaplastic carcinoma occurred in 25 per cent and around two thirds of these were of oat cell type. Adenocarcinoma was found in 22 per cent and the acinar type predominated. Bronchiolo-alveolar carcinoma occurred in 1 per cent and large cell carcinoma in 3 per cent. Typing of biopsy specimens was made in 289 cases in which a positive biopsy had been obtained during the pretreatment period. The result of the biopsy typing was checked against that of the final one. In the total group the preoperative histological diagnosis tallied with the final one in 88 per cent. In patients who had been subjected to surgery the pretreatment diagnosis of the epidermoid carcinoma was correct in 86 per cent, that of small cell anaplastic carcinoma in 92 per cent and that of adenocarcinoma in 100 per cent. The consistency was also high in the category of patients not subjected to surgery. Despite their critical attitude towards the delimitation of epidermoid carcinoma in the WHO-classification the present authors find it to be a reliable guide to routine typing of lung cancer.", "contents": "Histological typing of lung cancer. Application of the World Health Organization classification to 479 cases. Four hundred and seventy nine primary lung cancers were typed according to the WHO histological classification. The character of the material and the methods of investigation are described. All patients had been subjected to mediastinoscopy and 313 patients had been operated upon. Nearly half of the tumours (48 per cent) was epidermoid carcinomas. Small cell anaplastic carcinoma occurred in 25 per cent and around two thirds of these were of oat cell type. Adenocarcinoma was found in 22 per cent and the acinar type predominated. Bronchiolo-alveolar carcinoma occurred in 1 per cent and large cell carcinoma in 3 per cent. Typing of biopsy specimens was made in 289 cases in which a positive biopsy had been obtained during the pretreatment period. The result of the biopsy typing was checked against that of the final one. In the total group the preoperative histological diagnosis tallied with the final one in 88 per cent. In patients who had been subjected to surgery the pretreatment diagnosis of the epidermoid carcinoma was correct in 86 per cent, that of small cell anaplastic carcinoma in 92 per cent and that of adenocarcinoma in 100 per cent. The consistency was also high in the category of patients not subjected to surgery. Despite their critical attitude towards the delimitation of epidermoid carcinoma in the WHO-classification the present authors find it to be a reliable guide to routine typing of lung cancer."}
{"id": "PMID:187007", "title": "Biological conditions influencing the focal necrotic hepatitis test for differentiation between herpes simplex virus types 1 and 2.", "content": "Some biological conditions of the focal necrotic hepatitis test for the differentiation between herpes simplex virus (HSV) types 1 and 2 were investigated. Most of 13 different strains of mice tested were found usable in the test. An upper age limit (4 weeks) for the appearance of focal necrotic liver lesions was found in one strain of mice, while this was not seen in another strain. The minimum dose in 3- to 4-week-old mice was found to be as small as 10(2) to 10(3) p.f.u. in 0.1 ml of diluent. Suckling rats and hamsters, aged up to 7 and 14 days, respectively, were found to be convenient as alternative test animals. Finally, it was observed that focal necrotic hepatitis did not develop in the nude mouse with thymic aplasia on intraperitoneal inoculation of HSV type 2. The possible involvement of the thymus in the pathogenesis of the focal necrotic lesions is briefly discussed.", "contents": "Biological conditions influencing the focal necrotic hepatitis test for differentiation between herpes simplex virus types 1 and 2. Some biological conditions of the focal necrotic hepatitis test for the differentiation between herpes simplex virus (HSV) types 1 and 2 were investigated. Most of 13 different strains of mice tested were found usable in the test. An upper age limit (4 weeks) for the appearance of focal necrotic liver lesions was found in one strain of mice, while this was not seen in another strain. The minimum dose in 3- to 4-week-old mice was found to be as small as 10(2) to 10(3) p.f.u. in 0.1 ml of diluent. Suckling rats and hamsters, aged up to 7 and 14 days, respectively, were found to be convenient as alternative test animals. Finally, it was observed that focal necrotic hepatitis did not develop in the nude mouse with thymic aplasia on intraperitoneal inoculation of HSV type 2. The possible involvement of the thymus in the pathogenesis of the focal necrotic lesions is briefly discussed."}
{"id": "PMID:187008", "title": "Functional and ultrastructural studies of the effects of human interferon on cell membranes of in vitro cultured cells.", "content": "The effect of human leukocyte interferon on cultured U-amnion cells was examined, and several biological parameters were registered. Multiplication of Vesicular stomatitis virus and the virus-produced cytopathogenic effect was prevented. The growth rate of uninfected cells was reduced, as well as the spontaneous release of 3H-uridine. These effects were observed following treatment with 10 units of interferon per ml. No morphological alterations could be detected by scanning electron microscopy after 24 or 72 hours treatment with up to 2000 units interferon per ml.", "contents": "Functional and ultrastructural studies of the effects of human interferon on cell membranes of in vitro cultured cells. The effect of human leukocyte interferon on cultured U-amnion cells was examined, and several biological parameters were registered. Multiplication of Vesicular stomatitis virus and the virus-produced cytopathogenic effect was prevented. The growth rate of uninfected cells was reduced, as well as the spontaneous release of 3H-uridine. These effects were observed following treatment with 10 units of interferon per ml. No morphological alterations could be detected by scanning electron microscopy after 24 or 72 hours treatment with up to 2000 units interferon per ml."}
{"id": "PMID:187009", "title": "Crossed immunoelectrophoretic analysis of Bordetella pertussis antigens and of corresponding antibodies in human sera.", "content": "Fourty-four antigens were demonstrated in sonicated preparations of Bordetella pertussis (B.p.), using crossed immunoelectrophoresis against antiserum obtained from rabbits. No qualititative differences between the four strains of the Danish pertussis vaccine were found. In preparations of B.p. culture medium, purified with respect to Lymphocytosis Promoting Factor (LPF) activity, one antigen was possibly related to LPF. In human sera, antibodies against five of the B.p. antigens were demonstrated by means of crossed immunoelectrophoresis with intermediate gel. Antibody production was demonstrable in children during the pertussis vaccination period and was most marked after the second vaccination.", "contents": "Crossed immunoelectrophoretic analysis of Bordetella pertussis antigens and of corresponding antibodies in human sera. Fourty-four antigens were demonstrated in sonicated preparations of Bordetella pertussis (B.p.), using crossed immunoelectrophoresis against antiserum obtained from rabbits. No qualititative differences between the four strains of the Danish pertussis vaccine were found. In preparations of B.p. culture medium, purified with respect to Lymphocytosis Promoting Factor (LPF) activity, one antigen was possibly related to LPF. In human sera, antibodies against five of the B.p. antigens were demonstrated by means of crossed immunoelectrophoresis with intermediate gel. Antibody production was demonstrable in children during the pertussis vaccination period and was most marked after the second vaccination."}
{"id": "PMID:187010", "title": "Cross-reactions between Bordetella pertussis and twenty-eight other bacterial species.", "content": "Cross-reactions between B. pertussis and 28 other bacterial species were studied by various quantitative immunoelectrophoretic methods. A sonicated B. pertussis antigen preparation and a corresponding pooled rabbit antiserum were used as reference system. Two of the B. pertussis antigens were cross-reactive with antigens from 17, respectively 19, other bacterial species mainly gram-negative species. As judged by absorption of antibodies, the degree of cross-reactivity of these B. pertussis antigens with antigens from other species was found to be in the range 25-30%. Antigens from B. parapertussis and B. bronchiseptica were found to cross-react very extensively with B. pertussis, and only 4, respectively 2, of the 44 antigens of the B. pertussis reference system could not be absorbed with antigens from these two Bordetella species.", "contents": "Cross-reactions between Bordetella pertussis and twenty-eight other bacterial species. Cross-reactions between B. pertussis and 28 other bacterial species were studied by various quantitative immunoelectrophoretic methods. A sonicated B. pertussis antigen preparation and a corresponding pooled rabbit antiserum were used as reference system. Two of the B. pertussis antigens were cross-reactive with antigens from 17, respectively 19, other bacterial species mainly gram-negative species. As judged by absorption of antibodies, the degree of cross-reactivity of these B. pertussis antigens with antigens from other species was found to be in the range 25-30%. Antigens from B. parapertussis and B. bronchiseptica were found to cross-react very extensively with B. pertussis, and only 4, respectively 2, of the 44 antigens of the B. pertussis reference system could not be absorbed with antigens from these two Bordetella species."}
{"id": "PMID:187011", "title": "An enterotoxin produced by Clostridium perfringens type D. Purification by affinity chromatography.", "content": "Clostridium perfringens type D 9867 produced enterotoxin immunologically identical to that produced by types A and C which are responsible for C. perfringens food poisoning. Enterotoxin from type C 5386 and type D 9867 was produced in Duncan og Strong sporulation medium (DS medium). The supernatant fluid from DS-cultures was used for purification of the enterotoxin by affinity chromatography on a monospecific anti-enterotoxin-coupled CNBr activated-Sepharose 4B and activated CH-Sepharose 4B column. The enterotoxin purified by this one-step procedure proved to be of a purity comparable to that obtained by conventional methods, and possessed lethal activity in mice.", "contents": "An enterotoxin produced by Clostridium perfringens type D. Purification by affinity chromatography. Clostridium perfringens type D 9867 produced enterotoxin immunologically identical to that produced by types A and C which are responsible for C. perfringens food poisoning. Enterotoxin from type C 5386 and type D 9867 was produced in Duncan og Strong sporulation medium (DS medium). The supernatant fluid from DS-cultures was used for purification of the enterotoxin by affinity chromatography on a monospecific anti-enterotoxin-coupled CNBr activated-Sepharose 4B and activated CH-Sepharose 4B column. The enterotoxin purified by this one-step procedure proved to be of a purity comparable to that obtained by conventional methods, and possessed lethal activity in mice."}
{"id": "PMID:187012", "title": "Identification of paramyxovirus-specific haemolysis-inhibiting antibodies separate from haemagglutinating-inhibiting and neuraminidase-inhibiting antibodies. 1. Sendai virus haemolysis-inhibiting antibodies.", "content": "Egg-grown Sendai virus was used for preparation of rabbit hyperimmune sera directed against purified whole virus and pronasetreated projectionless virus particles. These sera and convalescent sera after natural Sendai infection in guinea pigs were studied in haemolysis-inhibition (HLI), haemagglutination-inhibition (HI) and neuraminidase-inhibition (NI) tests both before and after absorption with Tween 80-ether (TE) treated virus preparations. In addition, neutralization tests using the different sera were carried out. HI and NI antibodies and the major population of neutralizing antibodies in convalescent sera were removed by absorption with TE treated virus material without changing the titre of non-HI HLI antibodies. Rabbit hyperimmune sera directed against projectionless virus particles exhibited HLI antibody titres in marked excess of HI and NI antibody titres, whereas this was not found in sera against purified whole virus. In contrast, absorption of sera against projectionless particles eliminated HI antibodies without changing the titre of non-HI HLI antibodies. The protein composition of antigenic preparations used in absorption experiments and for preparation of sera was investigated by SDS-polyacryladmie-gel electrophoresis. TH treatment had no significant effect on the polypeptide pattern of Sendai virus. Pronase-treatment predominantly affected the two glycosylated proteins of Sendai virus. The larger glycoprotein was not detectable in pronasetreated projectionless virus particles, whereas the smaller glycoprotein was present in reduced quantities.", "contents": "Identification of paramyxovirus-specific haemolysis-inhibiting antibodies separate from haemagglutinating-inhibiting and neuraminidase-inhibiting antibodies. 1. Sendai virus haemolysis-inhibiting antibodies. Egg-grown Sendai virus was used for preparation of rabbit hyperimmune sera directed against purified whole virus and pronasetreated projectionless virus particles. These sera and convalescent sera after natural Sendai infection in guinea pigs were studied in haemolysis-inhibition (HLI), haemagglutination-inhibition (HI) and neuraminidase-inhibition (NI) tests both before and after absorption with Tween 80-ether (TE) treated virus preparations. In addition, neutralization tests using the different sera were carried out. HI and NI antibodies and the major population of neutralizing antibodies in convalescent sera were removed by absorption with TE treated virus material without changing the titre of non-HI HLI antibodies. Rabbit hyperimmune sera directed against projectionless virus particles exhibited HLI antibody titres in marked excess of HI and NI antibody titres, whereas this was not found in sera against purified whole virus. In contrast, absorption of sera against projectionless particles eliminated HI antibodies without changing the titre of non-HI HLI antibodies. The protein composition of antigenic preparations used in absorption experiments and for preparation of sera was investigated by SDS-polyacryladmie-gel electrophoresis. TH treatment had no significant effect on the polypeptide pattern of Sendai virus. Pronase-treatment predominantly affected the two glycosylated proteins of Sendai virus. The larger glycoprotein was not detectable in pronasetreated projectionless virus particles, whereas the smaller glycoprotein was present in reduced quantities."}
{"id": "PMID:187013", "title": "Antibodies to synthetic ACTH in asthmatic and rheumatic patients.", "content": "The prevalence of antibodies against synthetic ACTH preparations and porcine gamma globulin was investigated in 29 asthmatic patients, in 28 rheumatic patients, and in 63 normal subjects of both sexes. Agglutinating antibodies were examined by a passive haemagglutination test and IgE antibodies by a radio-immuno assay. The incidence of agglutinating reactions against Synacth\u00e9n and porcine gamma globulin was significantly higher in the asthmatic and rheumatic groups than in the group of normal subjects. Titres were generally low, attaining supposedly pathological levels (larger than or equal to 1/200) in about 10 per cent of the asthmatic patients and in 20-40 per cent of the rheumatic patients. In asthmatic patients, the incidence of ACTH specific IgE was higher than that in the normal group. This difference was not statistically significant in patients on routine treatment but it became satistically significant after ACTH booster treatment. In rheumatic patients the incidence of IgE antibodies against ACTH was insignificantly lower than that in the normal group. The incidence of agglutinating antibodies against vasopressin in asthmatic and rheumatic patients was also increased as compared with that in normal subjects and the titres were positively correlated to those against ACTH.", "contents": "Antibodies to synthetic ACTH in asthmatic and rheumatic patients. The prevalence of antibodies against synthetic ACTH preparations and porcine gamma globulin was investigated in 29 asthmatic patients, in 28 rheumatic patients, and in 63 normal subjects of both sexes. Agglutinating antibodies were examined by a passive haemagglutination test and IgE antibodies by a radio-immuno assay. The incidence of agglutinating reactions against Synacth\u00e9n and porcine gamma globulin was significantly higher in the asthmatic and rheumatic groups than in the group of normal subjects. Titres were generally low, attaining supposedly pathological levels (larger than or equal to 1/200) in about 10 per cent of the asthmatic patients and in 20-40 per cent of the rheumatic patients. In asthmatic patients, the incidence of ACTH specific IgE was higher than that in the normal group. This difference was not statistically significant in patients on routine treatment but it became satistically significant after ACTH booster treatment. In rheumatic patients the incidence of IgE antibodies against ACTH was insignificantly lower than that in the normal group. The incidence of agglutinating antibodies against vasopressin in asthmatic and rheumatic patients was also increased as compared with that in normal subjects and the titres were positively correlated to those against ACTH."}
{"id": "PMID:187014", "title": "Responses of the denervated rat urinary bladder to alfa adrenoceptor stimulation.", "content": "The contractile responses of the rat detrusor muscle to noradrenaline were increased 2-3 weeks after partial denervation but had returned to control values 6-9 weeks after the denervation, probably because of reinnervation of denervated muscle cells. 6-9 weeks after partial denervation the excitatory alpha-adrenoceptor mediated response to stimulation of the remaining intact nerves was predominant, masking the subsequent inhibitory beta-receptor response, which at this time was seen only after alpha-receptor blockade. The possibility of an outgrowth of adrenergic fibres activating alpha-receptors in muscle cells normally not innervated by adrenergic nerves is discussed.", "contents": "Responses of the denervated rat urinary bladder to alfa adrenoceptor stimulation. The contractile responses of the rat detrusor muscle to noradrenaline were increased 2-3 weeks after partial denervation but had returned to control values 6-9 weeks after the denervation, probably because of reinnervation of denervated muscle cells. 6-9 weeks after partial denervation the excitatory alpha-adrenoceptor mediated response to stimulation of the remaining intact nerves was predominant, masking the subsequent inhibitory beta-receptor response, which at this time was seen only after alpha-receptor blockade. The possibility of an outgrowth of adrenergic fibres activating alpha-receptors in muscle cells normally not innervated by adrenergic nerves is discussed."}
{"id": "PMID:187016", "title": "Rescue of Rous sarcoma virus (RSV) from RSV-transformed human embryonic cells by cell fusion with chick embryo fibroblasts using lysolecithin.", "content": "Heterokaryon formation and Rous sarcoma virus (RSV)-induction were studied by fusion of RSV-transformed human embryonic cells with chick embryo fibroblasts in the presence of lysolecithin. Heterokaryon formation was observed by autoradiography. RSV-induction was identified by focus formation, electron microscopy and density gradient centrifugation of 3H-uridine-labeled particles. The most effective concentration of lysolecithin for virus induction was 10 mug/10(6) cells/0.1 ml. Efficiency of lysolecithin in virus induction was not less than that of ultraviolet-inactivated Sendai virus (UV-HVJ).", "contents": "Rescue of Rous sarcoma virus (RSV) from RSV-transformed human embryonic cells by cell fusion with chick embryo fibroblasts using lysolecithin. Heterokaryon formation and Rous sarcoma virus (RSV)-induction were studied by fusion of RSV-transformed human embryonic cells with chick embryo fibroblasts in the presence of lysolecithin. Heterokaryon formation was observed by autoradiography. RSV-induction was identified by focus formation, electron microscopy and density gradient centrifugation of 3H-uridine-labeled particles. The most effective concentration of lysolecithin for virus induction was 10 mug/10(6) cells/0.1 ml. Efficiency of lysolecithin in virus induction was not less than that of ultraviolet-inactivated Sendai virus (UV-HVJ)."}
{"id": "PMID:187018", "title": "Stereoelectrosubcorticography in epilepsy, the focus and epileptogenic system.", "content": "According to the conceptual electrophysiological model for epilepsy worked out by the authors earlier (1968-1971) the development of the disease has the following stages: \"epileptic\" neurone epileptogenic focus epileptogenic system epileptic brain. The mechanisms of the II and III stages are analysed in the given paper. The critical volume of the neuronal population capable of functioning as a triggering focus is shown to be 10(3)-10(5) cells (Microsystem). On the II stage the control is achieved by the lateral inhibition. Further on epileptogenic macrosystems and subsystems of discharge reverberation (vertical and horizontal) are formed with complex hierarchy on a reciprocal principle. A morpho-functional organization of pathological systems in petit mal, grand mal, uni- and bitemporal epilepsy was found during ictal and interictal periods. Inhibitory systems (low pontine and caudate) and reciprocal inhibition during the III stage were found to act as controls.", "contents": "Stereoelectrosubcorticography in epilepsy, the focus and epileptogenic system. According to the conceptual electrophysiological model for epilepsy worked out by the authors earlier (1968-1971) the development of the disease has the following stages: \"epileptic\" neurone epileptogenic focus epileptogenic system epileptic brain. The mechanisms of the II and III stages are analysed in the given paper. The critical volume of the neuronal population capable of functioning as a triggering focus is shown to be 10(3)-10(5) cells (Microsystem). On the II stage the control is achieved by the lateral inhibition. Further on epileptogenic macrosystems and subsystems of discharge reverberation (vertical and horizontal) are formed with complex hierarchy on a reciprocal principle. A morpho-functional organization of pathological systems in petit mal, grand mal, uni- and bitemporal epilepsy was found during ictal and interictal periods. Inhibitory systems (low pontine and caudate) and reciprocal inhibition during the III stage were found to act as controls."}
{"id": "PMID:187022", "title": "Lymphocyte subpopulations: analysis of T-cell rosette characters.", "content": "The data indicated that 2 populations of thymocytes existed: immature and mature types, identifiable by their rosette characters. The immature type was capable of changing spontaneously to the mature type, but was partially suppressed in vivo by the high concentration of thymic hormone present in the intrathymic environment. The mature types of thymocytes emigrated to the peripheral organ, accounting for their high percentage of small rosettes. Alternately, cells of peripheral organs might have originated from the immature type in the thymus. Once emigrated and exposed to a lower concentration of thymic hormone, they changed into the mature pattern. The fact that lymph node rosettes were less affected by culture in vitro indicated that once cells have changed to the mature pattern they have less ground for further differentiation.", "contents": "Lymphocyte subpopulations: analysis of T-cell rosette characters. The data indicated that 2 populations of thymocytes existed: immature and mature types, identifiable by their rosette characters. The immature type was capable of changing spontaneously to the mature type, but was partially suppressed in vivo by the high concentration of thymic hormone present in the intrathymic environment. The mature types of thymocytes emigrated to the peripheral organ, accounting for their high percentage of small rosettes. Alternately, cells of peripheral organs might have originated from the immature type in the thymus. Once emigrated and exposed to a lower concentration of thymic hormone, they changed into the mature pattern. The fact that lymph node rosettes were less affected by culture in vitro indicated that once cells have changed to the mature pattern they have less ground for further differentiation."}
{"id": "PMID:187033", "title": "Molecular and kinetic properties of 15-hydroxyprostaglandin dehydrogenase (PG-15-HDH) from human placenta.", "content": "Some molecular properties of PG-15-HDH from human term placenta were investigated. Using a computer-based weighted linear regression analysis, intersecting initial rate patterns were received for the forward reaction with the prostaglandins (PG) E1, E2, and F2alpha, respectively, and NAD as substrates. NADH exerted a linear competitive inhibition with respect to NAD. The 15-ketoprostaglandins (15-keto-PG) E1 and F2alpha showed a linear noncompetitive inhibition with respect to their corresponding PG. The kinetic patterns suggest an ordered Bi Bi mechanism of PG-15-HDH reaction. The results are discussed with respect to their possible biological significance.", "contents": "Molecular and kinetic properties of 15-hydroxyprostaglandin dehydrogenase (PG-15-HDH) from human placenta. Some molecular properties of PG-15-HDH from human term placenta were investigated. Using a computer-based weighted linear regression analysis, intersecting initial rate patterns were received for the forward reaction with the prostaglandins (PG) E1, E2, and F2alpha, respectively, and NAD as substrates. NADH exerted a linear competitive inhibition with respect to NAD. The 15-ketoprostaglandins (15-keto-PG) E1 and F2alpha showed a linear noncompetitive inhibition with respect to their corresponding PG. The kinetic patterns suggest an ordered Bi Bi mechanism of PG-15-HDH reaction. The results are discussed with respect to their possible biological significance."}
{"id": "PMID:187034", "title": "Kinetic studies on 15-hydroxyprostaglandin dehydrogenase from human placenta.", "content": "The enzyme system 15-hydroxyprostaglandin dehydrogenase, which catalyzes the oxidation of the 15-hydroxy group of all naturally occurring prostaglandins, has been purified 1,270-fold by isoelectric focusing. Km values have been determined for prostaglandin E2 and NAD+ and were found to be 1 and 44 muM. The overall forward reaction was V1 = 450 nmol/min. Both the product 15-ketoprostaglandin E2 and the metabolite 13,14-dihydro-15-ketoprostaglandin E2 were noncompetitive inhibitors for the enzyme.", "contents": "Kinetic studies on 15-hydroxyprostaglandin dehydrogenase from human placenta. The enzyme system 15-hydroxyprostaglandin dehydrogenase, which catalyzes the oxidation of the 15-hydroxy group of all naturally occurring prostaglandins, has been purified 1,270-fold by isoelectric focusing. Km values have been determined for prostaglandin E2 and NAD+ and were found to be 1 and 44 muM. The overall forward reaction was V1 = 450 nmol/min. Both the product 15-ketoprostaglandin E2 and the metabolite 13,14-dihydro-15-ketoprostaglandin E2 were noncompetitive inhibitors for the enzyme."}
{"id": "PMID:187035", "title": "Kinetic evidence of a distinct regulatory site on 15-hydroxyprostaglandin dehydrogenase.", "content": "15-Hydroxyprostaglandin dehydrogenase was inhibited by xylocaine, furosemide, and ethacrynic acid, but was activated by imipramine and other related drugs. Inhibition by xylocaine was uncompetitive with respect to both NAD+ and PGE1. Activation by imipramine was also uncompetitive with respect to both substrates. Kinetic studies on mixed inhibitor and activator showed a competitive pattern of inhibition of xylocaine vs imipramine activation. These studies suggest that either inhibitors or activators interact with the enzyme at a site distinct from substrate and coenzyme binding sites, and that inhibitors and activators probably interact with the enzyme at the same regulatory site.", "contents": "Kinetic evidence of a distinct regulatory site on 15-hydroxyprostaglandin dehydrogenase. 15-Hydroxyprostaglandin dehydrogenase was inhibited by xylocaine, furosemide, and ethacrynic acid, but was activated by imipramine and other related drugs. Inhibition by xylocaine was uncompetitive with respect to both NAD+ and PGE1. Activation by imipramine was also uncompetitive with respect to both substrates. Kinetic studies on mixed inhibitor and activator showed a competitive pattern of inhibition of xylocaine vs imipramine activation. These studies suggest that either inhibitors or activators interact with the enzyme at a site distinct from substrate and coenzyme binding sites, and that inhibitors and activators probably interact with the enzyme at the same regulatory site."}
{"id": "PMID:187042", "title": "Stimulation by TSH of prostaglandin synthesis in pig thyroid.", "content": "The liberation of arachindonate in the thyroid occurs at the expense of two distinct pools of precursors. (1) the phosphatidylinositol through a process Ca2+-dependent and cyclic AMP-independent; and (2) the triglycerides by a cyclic AMP-dependent lipase, in which the involvement of cyclic AMP-dependent protein kinase has not yet been determined. The \"PI pool\" or \"paracyclic AMP pool\" is mobilized very rapidly by large doses of TSH but its physiological significance can be discussed. The \"triglyceride pool\" or \"post-cyclic AMP pool\" is mobilized more slowly by small doses of TSH and seems not to be implicated in the acute TSH stimulation of adenylate cyclase. The \"post-cyclic AMP pool\" of prostaglandins would be very important as third messenger or as \"long-acting TSH hormone\". Some recent works of Boeynaems and Van Sande (16) and Madaoui et al. (17) on the thyroid support this hypothesis, as aspirin or indomethacin inhibits DBc-AMP stimulation of glucose oxydation, iodine organification, or thyroid hormone secretion. On the other hand, in the absence of prostaglandin synthesis, TSH still stimulates the adenylate cyclase, which means that prostaglandins are not obligatory intermediates of hormonal action on cyclic AMP production. In conclusion, these results show a TSH action in the thyroid on the release of fatty acids, precursors of PG's, from their lipidic stores. Nevertheless, a second control step is not excluded in conversion of cyclic endoperoxide to PGE or PGFalpha.", "contents": "Stimulation by TSH of prostaglandin synthesis in pig thyroid. The liberation of arachindonate in the thyroid occurs at the expense of two distinct pools of precursors. (1) the phosphatidylinositol through a process Ca2+-dependent and cyclic AMP-independent; and (2) the triglycerides by a cyclic AMP-dependent lipase, in which the involvement of cyclic AMP-dependent protein kinase has not yet been determined. The \"PI pool\" or \"paracyclic AMP pool\" is mobilized very rapidly by large doses of TSH but its physiological significance can be discussed. The \"triglyceride pool\" or \"post-cyclic AMP pool\" is mobilized more slowly by small doses of TSH and seems not to be implicated in the acute TSH stimulation of adenylate cyclase. The \"post-cyclic AMP pool\" of prostaglandins would be very important as third messenger or as \"long-acting TSH hormone\". Some recent works of Boeynaems and Van Sande (16) and Madaoui et al. (17) on the thyroid support this hypothesis, as aspirin or indomethacin inhibits DBc-AMP stimulation of glucose oxydation, iodine organification, or thyroid hormone secretion. On the other hand, in the absence of prostaglandin synthesis, TSH still stimulates the adenylate cyclase, which means that prostaglandins are not obligatory intermediates of hormonal action on cyclic AMP production. In conclusion, these results show a TSH action in the thyroid on the release of fatty acids, precursors of PG's, from their lipidic stores. Nevertheless, a second control step is not excluded in conversion of cyclic endoperoxide to PGE or PGFalpha."}
{"id": "PMID:187043", "title": "Prostaglandin binding to membrane fractions from rat skin.", "content": "[3H]PGE2 and [3H]PGF2alpha bound to PM and ER prepared from rat skin with high affinity and specificity. Maximum binding was achieved in the presence of Ca2+ (5.0 x 10(-4) M). Unlabeled PGE2 and PGF2alpha inhibited [3H] PGE2alpha binding to ER in a dose-dependent manner with approximately 90% inhibition at a concentration of 1.5 x 10(-10) M. PGF2alpha inhibited approximately 40% of the same concentration. A variety of fatty acids inhibited binding less than 30% at 3.0 x 10(-10) M. The [3H]PGE2 binding was inactivated by pronase, trypsin, and heat treatment. Decreased specific binding of [3H]PGE2 to membrane fractions of EFA-deficient rats was demonstrated in our experiments, whereas binding of [3H]PGF2alpha was elevated. These results indicate that the abnormality of skin under EFA deficiency alters the ability of the membrane preparations to bind prostaglandins.", "contents": "Prostaglandin binding to membrane fractions from rat skin. [3H]PGE2 and [3H]PGF2alpha bound to PM and ER prepared from rat skin with high affinity and specificity. Maximum binding was achieved in the presence of Ca2+ (5.0 x 10(-4) M). Unlabeled PGE2 and PGF2alpha inhibited [3H] PGE2alpha binding to ER in a dose-dependent manner with approximately 90% inhibition at a concentration of 1.5 x 10(-10) M. PGF2alpha inhibited approximately 40% of the same concentration. A variety of fatty acids inhibited binding less than 30% at 3.0 x 10(-10) M. The [3H]PGE2 binding was inactivated by pronase, trypsin, and heat treatment. Decreased specific binding of [3H]PGE2 to membrane fractions of EFA-deficient rats was demonstrated in our experiments, whereas binding of [3H]PGF2alpha was elevated. These results indicate that the abnormality of skin under EFA deficiency alters the ability of the membrane preparations to bind prostaglandins."}
{"id": "PMID:187045", "title": "Inhibition of adenylate cyclase in adipocyte ghosts by the prostaglandin endoperoxide PGH2.", "content": "The prostaglandin endoperoxide PGH2 antagonized basal and hormone-stimulated adenylate cyclase activity in an adipocyte ghost preparation. The inhibition was readily reversible, and demonstrable on initial rates of cAMP synthesis. It is suggested that PGH2 may be an endogenous feedback regulator of lipolysis in adipose tissue.", "contents": "Inhibition of adenylate cyclase in adipocyte ghosts by the prostaglandin endoperoxide PGH2. The prostaglandin endoperoxide PGH2 antagonized basal and hormone-stimulated adenylate cyclase activity in an adipocyte ghost preparation. The inhibition was readily reversible, and demonstrable on initial rates of cAMP synthesis. It is suggested that PGH2 may be an endogenous feedback regulator of lipolysis in adipose tissue."}
{"id": "PMID:187046", "title": "Differential effects of prostaglandin synthetase inhibitors on prostaglandin E2 binding and on prostaglandin- or cholera toxin-induced cyclic AMP accumulation in the rabbit uterus.", "content": "Cyclic 3',5'-nucleotide phosphodiesterase (PDE) activity in rabbit uterine homogenate was inhibited by indomethacin (10 mug/ml; 66% inhibition) or flufenamic and (10 mug/ml; 60%). Indomethacin (100 mug/ml) reduced uterine prostaglandin E2 (PGE2) content by 80%, but potentiated the stimulatory action of purified cholera toxin (choleragen; 800%) and of exogenous PGE2 (140%) on cyclic AMP accumulation, probably through its inhibitory effect on cyclic AMP destruction. These findings suggest that endogenous PGE2 is not an essential mediator of choleragen action. By contrast, flufenamic acid abolished choleragen and PGE2 action on cyclic AMP production. Unlabeled PGE2 (10 mug/ml), flufenamic acid, indomethacin, and aspirin (100 mug/ml each) inhibited [3H]PGE2 binding to uterine slices by 78, 73, 62, and 20% respectively. It is concluded that while indomethacin and flufenamic acid have similar effects on prostaglandin biosynthesis and PDE activity, only fenamates have an inhibitory effect on the biological action of exogenous PGE2 and choleragen on the stimulation of cyclic AMP production, probably through the inhibition of the binding of PGE2 and choleragen to its specific receptor sites. The diverse biochemical actions of the above drugs indicate that care has to be taken when using these drugs in analyzing the physiopathological roles of prostaglandins.", "contents": "Differential effects of prostaglandin synthetase inhibitors on prostaglandin E2 binding and on prostaglandin- or cholera toxin-induced cyclic AMP accumulation in the rabbit uterus. Cyclic 3',5'-nucleotide phosphodiesterase (PDE) activity in rabbit uterine homogenate was inhibited by indomethacin (10 mug/ml; 66% inhibition) or flufenamic and (10 mug/ml; 60%). Indomethacin (100 mug/ml) reduced uterine prostaglandin E2 (PGE2) content by 80%, but potentiated the stimulatory action of purified cholera toxin (choleragen; 800%) and of exogenous PGE2 (140%) on cyclic AMP accumulation, probably through its inhibitory effect on cyclic AMP destruction. These findings suggest that endogenous PGE2 is not an essential mediator of choleragen action. By contrast, flufenamic acid abolished choleragen and PGE2 action on cyclic AMP production. Unlabeled PGE2 (10 mug/ml), flufenamic acid, indomethacin, and aspirin (100 mug/ml each) inhibited [3H]PGE2 binding to uterine slices by 78, 73, 62, and 20% respectively. It is concluded that while indomethacin and flufenamic acid have similar effects on prostaglandin biosynthesis and PDE activity, only fenamates have an inhibitory effect on the biological action of exogenous PGE2 and choleragen on the stimulation of cyclic AMP production, probably through the inhibition of the binding of PGE2 and choleragen to its specific receptor sites. The diverse biochemical actions of the above drugs indicate that care has to be taken when using these drugs in analyzing the physiopathological roles of prostaglandins."}
{"id": "PMID:187049", "title": "Inhibitory effects of prostaglandin E1 on responses of rabbit ear artery to nerve stimulation and on release of norepinephrine.", "content": "PGE1 in concentrations of 7 x 10(-9) to 4.5 x 10(-7) M inhibited the vasoconstrictor responses of the perfused rabbit ear artery to nerve stimulation. The degree of inhibition was dependent on the concentration of PGE1, as well as on the train length and frequency of stimulation. The vasoconstriction produced by norepinephrine was not altered by 1.1 x 10(-7) M PGE1. This substance markedly reduced the stimulation-evoked outflow of 3H-norepinephrine from the artery. The findings indicate that PGE1 inhibits the vasoconstrictor responses of rabbit ear artery to sympathetic nerve stimulation by reducing the release of the sympathetic transmitter for adrenergic nerve endings.", "contents": "Inhibitory effects of prostaglandin E1 on responses of rabbit ear artery to nerve stimulation and on release of norepinephrine. PGE1 in concentrations of 7 x 10(-9) to 4.5 x 10(-7) M inhibited the vasoconstrictor responses of the perfused rabbit ear artery to nerve stimulation. The degree of inhibition was dependent on the concentration of PGE1, as well as on the train length and frequency of stimulation. The vasoconstriction produced by norepinephrine was not altered by 1.1 x 10(-7) M PGE1. This substance markedly reduced the stimulation-evoked outflow of 3H-norepinephrine from the artery. The findings indicate that PGE1 inhibits the vasoconstrictor responses of rabbit ear artery to sympathetic nerve stimulation by reducing the release of the sympathetic transmitter for adrenergic nerve endings."}
{"id": "PMID:187051", "title": "Adrenocortical factors in hypertension. I. Significance of 18-hydroxy-11-deoxycorticosterone.", "content": "Low renin essential hypertension and the syndrome of mineralocorticoid excess have two features in common, low plasma renin activity and volume-sensitive hypertension. The proposal that both disorders share a common mechanism--because of the ability of agents that inhibit or antagonize the adrenocortical secretion to lower blood pressure in the low renin hypertensive group--appears to be based on a circular argument. The beneficial effect of removal or neutralization of the adrenocortical contribution only constitutes evidence for volume-dependency or sensitivity, which is how the low renin group is defined. Any measure that blocks a component of the normal homeostatic chain for the maintenance of extracellular and intravascular volume including the adrenal cortex would be expected to have a beneficial effect in volume-sensitive hypertension. Evidence for an adrenal factor in low renin hypertension must rest on the isolation of an active substance that reproduces the effect when readministered. 18-Hydroxy-11-deoxycorticosterone (18-OH-DOC) does not meet these criteria. It is not significantly increased in experimental hypertension and, although its overproduction in unselected low renin essential hypertensive patients remains controversial, the magnitude of the reported elevations is insufficient in relation to the low biologic activity of the steroid to account for a significant effect. Apart from its increase in the 17alpha-hydroxylase defect, 18-OH-DOC is increased in primary aldosteronism and may also be an indicator of a histologic variant of the aldosteronoma. On the basis of a large body of evidence showing parallelism between the 11beta- and 18-hydroxylase functions of the fasciculata zone, we have proposed that both enzymic functions are functionally related and may involve the same enzyme protein and catalytic site. According to this view, the secretion of 18-OH-DOC would have no special significance of its own but would be an obligatory consequence of the secretion of fasciculata zone corticosterone.", "contents": "Adrenocortical factors in hypertension. I. Significance of 18-hydroxy-11-deoxycorticosterone. Low renin essential hypertension and the syndrome of mineralocorticoid excess have two features in common, low plasma renin activity and volume-sensitive hypertension. The proposal that both disorders share a common mechanism--because of the ability of agents that inhibit or antagonize the adrenocortical secretion to lower blood pressure in the low renin hypertensive group--appears to be based on a circular argument. The beneficial effect of removal or neutralization of the adrenocortical contribution only constitutes evidence for volume-dependency or sensitivity, which is how the low renin group is defined. Any measure that blocks a component of the normal homeostatic chain for the maintenance of extracellular and intravascular volume including the adrenal cortex would be expected to have a beneficial effect in volume-sensitive hypertension. Evidence for an adrenal factor in low renin hypertension must rest on the isolation of an active substance that reproduces the effect when readministered. 18-Hydroxy-11-deoxycorticosterone (18-OH-DOC) does not meet these criteria. It is not significantly increased in experimental hypertension and, although its overproduction in unselected low renin essential hypertensive patients remains controversial, the magnitude of the reported elevations is insufficient in relation to the low biologic activity of the steroid to account for a significant effect. Apart from its increase in the 17alpha-hydroxylase defect, 18-OH-DOC is increased in primary aldosteronism and may also be an indicator of a histologic variant of the aldosteronoma. On the basis of a large body of evidence showing parallelism between the 11beta- and 18-hydroxylase functions of the fasciculata zone, we have proposed that both enzymic functions are functionally related and may involve the same enzyme protein and catalytic site. According to this view, the secretion of 18-OH-DOC would have no special significance of its own but would be an obligatory consequence of the secretion of fasciculata zone corticosterone."}
{"id": "PMID:187052", "title": "Short term study of sucrose polyester a nonabsorbable fat-like material as a dietary agent for lowering plasma cholesterol.", "content": "The efficacy, safety, and acceptability of sucrose polyester (SPE), a fat-like material that is neither digested nor absorbed, were assessed in 13 normal and seven hypercholesterolemic subjects for its potential as a cholesterol-lowering agent. Addition or substitution of SPE for culinary fats in the diets of the normocholesterolemic individuals produced a mean reduction of total and low-density lipoprotein cholesterol of 14 and 17%, respectively (P less than 0.001), despite the daily ingestion of a diet containing 800 mg of cholesterol and of dietary fat with a P/S ratio of 0.4. Total and low-density lipoprotein cholesterol were not significantly reduced by similar 10-day feeding periods of SPE in seven subjects with familial hypercholesterolemia. High-density lipoprotein cholesterol and triglycerides were not changed in normal or hypercholesterolemic subject receiving SPE. Plasma vitamin A and E levels were reduced by 10 and 21% (p less than 0.02 and less than 0.001) in both normal and hypercholesterolemic subjects on SPE. These returned to the basal levels when SPE consumption was discontinued. SPE was recovered quantitatively (greater than 97%) in the stools, with the last measurable SPE being found day 3 to 5 after cessation of SPE intake. Despite recovery of 50 g or more of unhydrolyzed SPE in stools during SPE feeding, there was no clinical or chemical steatorrhea. On subtracting SPE's input to total stool fatty acids, it was found that \"non-SPE\" fatty acids in the stool had not increased during SPE feeding, SPE was easily incorporated into routine foodstuffs in addition to, or in substitution for, conventional dietary fats. On the basis of this short term evaluation in humans and other investigations with the rat and dog. SPE appears to have potential as a cholesterol-lowering agent.", "contents": "Short term study of sucrose polyester a nonabsorbable fat-like material as a dietary agent for lowering plasma cholesterol. The efficacy, safety, and acceptability of sucrose polyester (SPE), a fat-like material that is neither digested nor absorbed, were assessed in 13 normal and seven hypercholesterolemic subjects for its potential as a cholesterol-lowering agent. Addition or substitution of SPE for culinary fats in the diets of the normocholesterolemic individuals produced a mean reduction of total and low-density lipoprotein cholesterol of 14 and 17%, respectively (P less than 0.001), despite the daily ingestion of a diet containing 800 mg of cholesterol and of dietary fat with a P/S ratio of 0.4. Total and low-density lipoprotein cholesterol were not significantly reduced by similar 10-day feeding periods of SPE in seven subjects with familial hypercholesterolemia. High-density lipoprotein cholesterol and triglycerides were not changed in normal or hypercholesterolemic subject receiving SPE. Plasma vitamin A and E levels were reduced by 10 and 21% (p less than 0.02 and less than 0.001) in both normal and hypercholesterolemic subjects on SPE. These returned to the basal levels when SPE consumption was discontinued. SPE was recovered quantitatively (greater than 97%) in the stools, with the last measurable SPE being found day 3 to 5 after cessation of SPE intake. Despite recovery of 50 g or more of unhydrolyzed SPE in stools during SPE feeding, there was no clinical or chemical steatorrhea. On subtracting SPE's input to total stool fatty acids, it was found that \"non-SPE\" fatty acids in the stool had not increased during SPE feeding, SPE was easily incorporated into routine foodstuffs in addition to, or in substitution for, conventional dietary fats. On the basis of this short term evaluation in humans and other investigations with the rat and dog. SPE appears to have potential as a cholesterol-lowering agent."}
{"id": "PMID:187053", "title": "Metabolism of vitamin D: current status.", "content": "There has been much progress in our understanding of the metabolism of vitamin D. It is now clear that vitamin D3 can be produced in the skin or ingested in the diet. It accumulates very rapidly in the liver where it undergoes 25-hydroxylation, yielding 25-OH-D3, the major circulating metabolite of the vitamin. 25-OH-D3 proceeds to the kidney where it undergoes one of two hydroxylations. If there is a biological need for calcium or for phosphate the kidney is stimulated to convert 25-OH-D3 to the 1,25-(OH)2-D3, a calcium and phosphate mobilizing hormone. If, however, the animal has sufficient supplies of calcium and phosphate, the l-hydroxylase is shut down and instead the 25-OH-D3 is converted to a 24,25-(OH)2D3. The role of the 24,25-(OH)2D3 remains unknown; it may be an intermediate in the inactivation-excretion mechanism. 1,25-(OH)2D3 proceeds to the intestine where it stimulates intestinal calcium transport and intestinal phosphate transport. It also stimulates bone calcium mobilization and probably has other effects yet to be discovered in such tissues as muscle. The 25-OH-D3-l-hydroxylase, which is located exclusively in renal mitochondria, has been shown to be a three component system involving a flavoprotein, an iron-sulfur protein (renal ferredoxin), and a cytochrome P-450. This system has been successfully solubilized, the components isolated, and reconstituted. The 24-hydroxylase, however, has not yet been thoroughly studied. 1,25-(OH)2D3 is necessary for the appearance of the 24-hydroxylase; parathyroid hormone represses 24-hydroxylation. It is possible that the 24-hydroxylase represents the major regulated enzyme, so that its presence or absence may determine whether 1,25-(OH)2D3 is produced. Two metabolic pathways for 1,25-(OH)2D3 are known, conversion by the 24-hydroxylase to 1,24,25-(OH)3D3, and conversion of 1,25-(OH)2D3 to an unknown substance. In the latter instance, there occurs loss of a side chain piece, including at least one of the 26 and 27 carbons. Whether 1,25-(OH)2D3 must be metabolized further before it carries out all of its functions has yet to be established. The primary excretion route of vitamin D3 is via the bile into the feces. Urinary excretion appears small in magnitude and no excretion products have yet been identified positively. Much remains to be learned concerning the metabolism and function of vitamin D and its metabolites. This should therefore, prove to be a fruitful area of investigation for many years to come, especially since 1,25-(OH)2D3, 25-OH-D3, and lalpha-OH-D3 have been shown to be effective in a number of metabolic bone disease states.", "contents": "Metabolism of vitamin D: current status. There has been much progress in our understanding of the metabolism of vitamin D. It is now clear that vitamin D3 can be produced in the skin or ingested in the diet. It accumulates very rapidly in the liver where it undergoes 25-hydroxylation, yielding 25-OH-D3, the major circulating metabolite of the vitamin. 25-OH-D3 proceeds to the kidney where it undergoes one of two hydroxylations. If there is a biological need for calcium or for phosphate the kidney is stimulated to convert 25-OH-D3 to the 1,25-(OH)2-D3, a calcium and phosphate mobilizing hormone. If, however, the animal has sufficient supplies of calcium and phosphate, the l-hydroxylase is shut down and instead the 25-OH-D3 is converted to a 24,25-(OH)2D3. The role of the 24,25-(OH)2D3 remains unknown; it may be an intermediate in the inactivation-excretion mechanism. 1,25-(OH)2D3 proceeds to the intestine where it stimulates intestinal calcium transport and intestinal phosphate transport. It also stimulates bone calcium mobilization and probably has other effects yet to be discovered in such tissues as muscle. The 25-OH-D3-l-hydroxylase, which is located exclusively in renal mitochondria, has been shown to be a three component system involving a flavoprotein, an iron-sulfur protein (renal ferredoxin), and a cytochrome P-450. This system has been successfully solubilized, the components isolated, and reconstituted. The 24-hydroxylase, however, has not yet been thoroughly studied. 1,25-(OH)2D3 is necessary for the appearance of the 24-hydroxylase; parathyroid hormone represses 24-hydroxylation. It is possible that the 24-hydroxylase represents the major regulated enzyme, so that its presence or absence may determine whether 1,25-(OH)2D3 is produced. Two metabolic pathways for 1,25-(OH)2D3 are known, conversion by the 24-hydroxylase to 1,24,25-(OH)3D3, and conversion of 1,25-(OH)2D3 to an unknown substance. In the latter instance, there occurs loss of a side chain piece, including at least one of the 26 and 27 carbons. Whether 1,25-(OH)2D3 must be metabolized further before it carries out all of its functions has yet to be established. The primary excretion route of vitamin D3 is via the bile into the feces. Urinary excretion appears small in magnitude and no excretion products have yet been identified positively. Much remains to be learned concerning the metabolism and function of vitamin D and its metabolites. This should therefore, prove to be a fruitful area of investigation for many years to come, especially since 1,25-(OH)2D3, 25-OH-D3, and lalpha-OH-D3 have been shown to be effective in a number of metabolic bone disease states."}
{"id": "PMID:187055", "title": "Advances in vitamin D metabolism as they pertain to chronic renal disease.", "content": "Many clinical similarities between renal osteodystrophy and nutritional rickets have suggested that a defect in either the metabolism or action of vitamin D exists in chronic renal failure. The discovery of the kidney as the organ that manufactures the active metabolite of vitamin D has provided direct evidence for a relationship between renal failure and altered vitamin D metabolism. Other observations suggest that an abnormality of vitamin D action could underlie both osteomalacia and osteitis fibrosa (secondary hyperparathyroidism) observed in patients with chronic renal failure. The administration of the active vitamin D analogs, 25(OH)D3, 1,25(OH)2D3, and lalpha(OH)D3, to uremic patients with symptomatic bone disease is capable of reversing many of the abnormalities of divalent ion metabolism. The widespread availability of these agents in the future may provide the clinician the means to correct or even prevent the serious bone disease that frequently complicates the course of chronic renal failure.", "contents": "Advances in vitamin D metabolism as they pertain to chronic renal disease. Many clinical similarities between renal osteodystrophy and nutritional rickets have suggested that a defect in either the metabolism or action of vitamin D exists in chronic renal failure. The discovery of the kidney as the organ that manufactures the active metabolite of vitamin D has provided direct evidence for a relationship between renal failure and altered vitamin D metabolism. Other observations suggest that an abnormality of vitamin D action could underlie both osteomalacia and osteitis fibrosa (secondary hyperparathyroidism) observed in patients with chronic renal failure. The administration of the active vitamin D analogs, 25(OH)D3, 1,25(OH)2D3, and lalpha(OH)D3, to uremic patients with symptomatic bone disease is capable of reversing many of the abnormalities of divalent ion metabolism. The widespread availability of these agents in the future may provide the clinician the means to correct or even prevent the serious bone disease that frequently complicates the course of chronic renal failure."}
{"id": "PMID:187057", "title": "Adrenocortical-related maturational events in the fetus.", "content": "In various organs in fetal animals, maturation is inducible by corticosteroids and delayed by hypophysectomy. A surge of corticosteroid in the fetal circulation preceding parturition may cause rapid organ maturation and enhanced viability. Since this phase of accelerated maturation is linked to the parturitional mechanisms, the changes can be termed collectively \"preparation for birth.\" Support for similar adrenocortical-related maturation of organs in the human fetus is less clear-cut. Nevertheless, evidence is accumulating to suggest that a similar concept can be usefully applied in man.", "contents": "Adrenocortical-related maturational events in the fetus. In various organs in fetal animals, maturation is inducible by corticosteroids and delayed by hypophysectomy. A surge of corticosteroid in the fetal circulation preceding parturition may cause rapid organ maturation and enhanced viability. Since this phase of accelerated maturation is linked to the parturitional mechanisms, the changes can be termed collectively \"preparation for birth.\" Support for similar adrenocortical-related maturation of organs in the human fetus is less clear-cut. Nevertheless, evidence is accumulating to suggest that a similar concept can be usefully applied in man."}
{"id": "PMID:187058", "title": "Dynamics of adenosine-3', 5'- monophosphate transfer among mother, fetus, and amniotic fluid in the rhesus monkey.", "content": "Cyclic AMP exchange among the mother, amniotic fluid, and fetus was studied in normal rhesus monkeys at term pregnancy. Following a pulse intravenous administration of 3H-cyclic AMP into the mother, a small fraction of the dose appeared in less than 1 minute in fetal blood. It appeared in the amniotic fluid after 5 minutes and reached maximum level in 20 minutes. The accumulation of 3H-cyclic AMP in the amniotic fluid in 1 hour was 0.03 per cent of the injected dose. The amount and time course of 3H-cyclic AMP accumulation in the fluid were not altered by tying the umbilical vessels. The transfer of 3H-cyclic AMP injected in utero into the fetal femoral artery resembled that in the mother; in 1 hour the amniotic fluid contained 0.22 per cent of the injected dose. When injected directly into the amniotic sac, more than 65 per cent of the injected dose remained unchanged after 1 hour, with minimal transfer into the maternal and fetal compartments. This study showed rapid bidirectional exchange of cyclic AMP between the mother and the fetus. Both of these compartments can contribute cyclic AMP to the amniotic fluid, independently or in concert. It remained fairly stable in the fluid and was not readily metabolized or transported out.", "contents": "Dynamics of adenosine-3', 5'- monophosphate transfer among mother, fetus, and amniotic fluid in the rhesus monkey. Cyclic AMP exchange among the mother, amniotic fluid, and fetus was studied in normal rhesus monkeys at term pregnancy. Following a pulse intravenous administration of 3H-cyclic AMP into the mother, a small fraction of the dose appeared in less than 1 minute in fetal blood. It appeared in the amniotic fluid after 5 minutes and reached maximum level in 20 minutes. The accumulation of 3H-cyclic AMP in the amniotic fluid in 1 hour was 0.03 per cent of the injected dose. The amount and time course of 3H-cyclic AMP accumulation in the fluid were not altered by tying the umbilical vessels. The transfer of 3H-cyclic AMP injected in utero into the fetal femoral artery resembled that in the mother; in 1 hour the amniotic fluid contained 0.22 per cent of the injected dose. When injected directly into the amniotic sac, more than 65 per cent of the injected dose remained unchanged after 1 hour, with minimal transfer into the maternal and fetal compartments. This study showed rapid bidirectional exchange of cyclic AMP between the mother and the fetus. Both of these compartments can contribute cyclic AMP to the amniotic fluid, independently or in concert. It remained fairly stable in the fluid and was not readily metabolized or transported out."}
{"id": "PMID:187059", "title": "Use of vidarabine in epidemic keratoconjunctivitis due to adenovirus types 3, 7, 8, and 19.", "content": "Adenovirus types 3,7,8, and 19 were isolated during an outbreak of epidemic keratoconjunctivitis. There was no clinically recognizable difference in the severity of the disease produced by each adenovirus type. Twenty-nine patients with positive viral cultures were given either 3.3% vidarabine ointment or polyvinyl alcohol eyedrops within five days of the onset od disease, and were observed for at least 14 days. An observer unaware of which medication was prescribed found subepithelial corneal infiltrates in 81% of vidarabine-treated patients and in 63% of control subjects. Vidarabine was ineffective in preventing subepithelial corneal infiltrates in keratoconjunctivitis caused by adenovirus.", "contents": "Use of vidarabine in epidemic keratoconjunctivitis due to adenovirus types 3, 7, 8, and 19. Adenovirus types 3,7,8, and 19 were isolated during an outbreak of epidemic keratoconjunctivitis. There was no clinically recognizable difference in the severity of the disease produced by each adenovirus type. Twenty-nine patients with positive viral cultures were given either 3.3% vidarabine ointment or polyvinyl alcohol eyedrops within five days of the onset od disease, and were observed for at least 14 days. An observer unaware of which medication was prescribed found subepithelial corneal infiltrates in 81% of vidarabine-treated patients and in 63% of control subjects. Vidarabine was ineffective in preventing subepithelial corneal infiltrates in keratoconjunctivitis caused by adenovirus."}
{"id": "PMID:187060", "title": "Herpetic stromal keratitis-evidence for cell-mediated immunopathogenesis.", "content": "Immunofluorescence, histological, and electron microscopic observations were made on rabbit corneas from animals with experimentally induced stromal keratitis following intracorneal injection with the RE strain of herpes simplex virus. Electron microscopic observations were also made on human corneas obtained from patients with a history of herpetic stromal disease. Viral antigens were demonstrated by immunofluorescence in keratocytes of rabbit corneas with herpetic stromal keratitis. Electron microscopic observations and viral culture failed to reveal the presence of viral particles in these tissues. Lymphocytes, a major infiltrating cell type found in both the rabbit and human corneas, were often found in intimate contact with degenerating keratocytes.", "contents": "Herpetic stromal keratitis-evidence for cell-mediated immunopathogenesis. Immunofluorescence, histological, and electron microscopic observations were made on rabbit corneas from animals with experimentally induced stromal keratitis following intracorneal injection with the RE strain of herpes simplex virus. Electron microscopic observations were also made on human corneas obtained from patients with a history of herpetic stromal disease. Viral antigens were demonstrated by immunofluorescence in keratocytes of rabbit corneas with herpetic stromal keratitis. Electron microscopic observations and viral culture failed to reveal the presence of viral particles in these tissues. Lymphocytes, a major infiltrating cell type found in both the rabbit and human corneas, were often found in intimate contact with degenerating keratocytes."}
{"id": "PMID:187061", "title": "En bloc removal of intrinsic neoplasms of the lacrimal gland.", "content": "The management of intrinsic neoplasms primary in the lacrimal gland is of serious concern because some of the most malignant primary tumors of the orbit occur in this glandular structure and present surgical techniques may easily disseminate the neoplasm and contribute to death or recurrences. We propose a surgical approach in which the tumor and adjacent adnexa are removed in a one-stage procedure, that is, an en bloc resection of the neoplasm, its periorbital base, and surrounding bone. This technique will minimize seeding of the tumor, provide a more complete eradication of the neoplasm without loss of the eye, and assure either a cure or a longer interval free of local recurrences or metastasis than is presently attainable.", "contents": "En bloc removal of intrinsic neoplasms of the lacrimal gland. The management of intrinsic neoplasms primary in the lacrimal gland is of serious concern because some of the most malignant primary tumors of the orbit occur in this glandular structure and present surgical techniques may easily disseminate the neoplasm and contribute to death or recurrences. We propose a surgical approach in which the tumor and adjacent adnexa are removed in a one-stage procedure, that is, an en bloc resection of the neoplasm, its periorbital base, and surrounding bone. This technique will minimize seeding of the tumor, provide a more complete eradication of the neoplasm without loss of the eye, and assure either a cure or a longer interval free of local recurrences or metastasis than is presently attainable."}
{"id": "PMID:187062", "title": "Impaired microtubule function correctable by cyclic GMP and cholinergic agonists in the Chediak-Higashi syndrome.", "content": "The Chediak-Higashi (CH) syndrome of man and several animal species is characterized by the presence of abnormal giant granules in all granule-containing cells and by defects in chemotaxis and lysosomal degranulation during phagocytosis in polymorphonuclear leukocytes (PMNs). Since similar functional abnormalities have been reported in normal PMNs following exposure to colchicine and other agents that disrupt microtubles it was proposed that microtubule function may be impaired in the CH syndrome. The mobility of concanavalin A (con A)-receptor complexes on PMN membranes was used to test microtubule integrity. Normal PMNs showed a uniform distribution of membrane-bound con A. By contrast, con A was aggregated into surface caps on both colchicine-treated normal PMNs and untreated PMNs from mice and a patient with CH syndrome. This result is consistent with impaired microtubule function in the CH cells. The spontaneous capping response of CH PMNs was inhibited by cyclic GMP and by cholinergic agonists that can elevate cyclic GMP levels in neutrophils. This raised the possibility that the microtubule defect in CH cells may be correctable by treatments that increase cyclic GMP generation. Direct evidence for both the absence of microtubule assembly in con A-treated PMNs from the CH patient and for normal microtubule assembly in CH PMNs incubated with cyclic GMP and cholinergic agonists prior to con A treatment was obtained by electron microscopy. In addition, evidence for a direct relationship between the microtubule defect and the development of giant lysosomes in CH cells was obtained. Thus, CH fibroblasts grown in vitro developed abnormal lysosomes in the majority of cells. However, the same cells cultured in the presence of cholinergic agonists developed a majority of lysosomes that were morphologically normal at the level of the light microscope. Similarly, granule morphology appeared normal in peripheral blood leukocytes from mice treated chronically in vivo with cholinergic agonists.", "contents": "Impaired microtubule function correctable by cyclic GMP and cholinergic agonists in the Chediak-Higashi syndrome. The Chediak-Higashi (CH) syndrome of man and several animal species is characterized by the presence of abnormal giant granules in all granule-containing cells and by defects in chemotaxis and lysosomal degranulation during phagocytosis in polymorphonuclear leukocytes (PMNs). Since similar functional abnormalities have been reported in normal PMNs following exposure to colchicine and other agents that disrupt microtubles it was proposed that microtubule function may be impaired in the CH syndrome. The mobility of concanavalin A (con A)-receptor complexes on PMN membranes was used to test microtubule integrity. Normal PMNs showed a uniform distribution of membrane-bound con A. By contrast, con A was aggregated into surface caps on both colchicine-treated normal PMNs and untreated PMNs from mice and a patient with CH syndrome. This result is consistent with impaired microtubule function in the CH cells. The spontaneous capping response of CH PMNs was inhibited by cyclic GMP and by cholinergic agonists that can elevate cyclic GMP levels in neutrophils. This raised the possibility that the microtubule defect in CH cells may be correctable by treatments that increase cyclic GMP generation. Direct evidence for both the absence of microtubule assembly in con A-treated PMNs from the CH patient and for normal microtubule assembly in CH PMNs incubated with cyclic GMP and cholinergic agonists prior to con A treatment was obtained by electron microscopy. In addition, evidence for a direct relationship between the microtubule defect and the development of giant lysosomes in CH cells was obtained. Thus, CH fibroblasts grown in vitro developed abnormal lysosomes in the majority of cells. However, the same cells cultured in the presence of cholinergic agonists developed a majority of lysosomes that were morphologically normal at the level of the light microscope. Similarly, granule morphology appeared normal in peripheral blood leukocytes from mice treated chronically in vivo with cholinergic agonists."}
{"id": "PMID:187064", "title": "Effectiveness of community services for discharged mental hospital patients.", "content": "This study of 579 state hospital patients charts the pattern of their care in the community in the two or three years following hospital discharge, and examines the relationship of aftercare services to readmission rates. Findings suggest that, among the most chronic patients, a substantial number of aftercare visits may be related to lower hospital readmission rates.", "contents": "Effectiveness of community services for discharged mental hospital patients. This study of 579 state hospital patients charts the pattern of their care in the community in the two or three years following hospital discharge, and examines the relationship of aftercare services to readmission rates. Findings suggest that, among the most chronic patients, a substantial number of aftercare visits may be related to lower hospital readmission rates."}
{"id": "PMID:187065", "title": "Some secular changes in the growth of American-born and native Japanese children.", "content": "Three hundred and sixteen (35%) of the American-born Japanese children whose height, weight, and skeletal age were recorded in 1956-57 were reexamined as young adults between 1968 and 1974, when they were found to be taller, heavier and shorter legged than men and women in Japan who were born in the same years as they. These differences between the American-born and the native Japanese adults were relatively smaller than they had been during childhood, due to both an acceleration in the growth rate of the native Japanese and a concomitant decline in that of the American-born Japanese during the intervening years. A comparison of our 1956-57 data with Kondo and Eto's findings in Los Angeles in 1971 shows that there has been very little increase in the size of California-Japanese children since 1956. The curves of average heights of native Japanese children 6 to 20 years of age, at 10-year intervals from 1900 to 1970, disclosed the changing rate at which they grew during different decates of that period. Those curves and other data discussed in this paper provide additional evidence of the biological superiority of the human female as compared with the male.", "contents": "Some secular changes in the growth of American-born and native Japanese children. Three hundred and sixteen (35%) of the American-born Japanese children whose height, weight, and skeletal age were recorded in 1956-57 were reexamined as young adults between 1968 and 1974, when they were found to be taller, heavier and shorter legged than men and women in Japan who were born in the same years as they. These differences between the American-born and the native Japanese adults were relatively smaller than they had been during childhood, due to both an acceleration in the growth rate of the native Japanese and a concomitant decline in that of the American-born Japanese during the intervening years. A comparison of our 1956-57 data with Kondo and Eto's findings in Los Angeles in 1971 shows that there has been very little increase in the size of California-Japanese children since 1956. The curves of average heights of native Japanese children 6 to 20 years of age, at 10-year intervals from 1900 to 1970, disclosed the changing rate at which they grew during different decates of that period. Those curves and other data discussed in this paper provide additional evidence of the biological superiority of the human female as compared with the male."}
{"id": "PMID:187066", "title": "Phosphorylation of cardiac regulatory proteins by cyclic AMP-dependent protein kinase.", "content": "Cardiac myofibrils were purified from canine myocardium, and the regulatory proteins (troponin + tropomyosin) were extracted and shown to contain endogenous cyclic AMP-dependent protein kinase activity. Other cyclic nucleotide stimulated the protein kinase activity but only at higher concentrations. The enzyme was able to catalyze phosphorylation of conventional substrates such as histones and casein as well as a component of the regulatory protein fraction with a molecular weight of 28,000 daltons. Endogenous phosphorylation required the presence of Mg2+ and was inhibited by Ca2+. A protein kinase inhibitor obtained from skeletal muscle inhibited the cyclicAMP-dependent phosphorylation. Escherichia coli alkaline phosphatase dephosphorylated the endogenous substrates. The level of phosphorylation found is severalfold higher than we have previously reported. A protein kinase, with its close association with the regulatory proteins, seems to be well suited to transmitting the message from the cyclic AMP to the regulatory proteins, a phenomenon that may influence the cardiac contractility via the troponin phosphorylation. The inhibitory effect of troponin on actomyosin might be changed by its state of phosphorylation.", "contents": "Phosphorylation of cardiac regulatory proteins by cyclic AMP-dependent protein kinase. Cardiac myofibrils were purified from canine myocardium, and the regulatory proteins (troponin + tropomyosin) were extracted and shown to contain endogenous cyclic AMP-dependent protein kinase activity. Other cyclic nucleotide stimulated the protein kinase activity but only at higher concentrations. The enzyme was able to catalyze phosphorylation of conventional substrates such as histones and casein as well as a component of the regulatory protein fraction with a molecular weight of 28,000 daltons. Endogenous phosphorylation required the presence of Mg2+ and was inhibited by Ca2+. A protein kinase inhibitor obtained from skeletal muscle inhibited the cyclicAMP-dependent phosphorylation. Escherichia coli alkaline phosphatase dephosphorylated the endogenous substrates. The level of phosphorylation found is severalfold higher than we have previously reported. A protein kinase, with its close association with the regulatory proteins, seems to be well suited to transmitting the message from the cyclic AMP to the regulatory proteins, a phenomenon that may influence the cardiac contractility via the troponin phosphorylation. The inhibitory effect of troponin on actomyosin might be changed by its state of phosphorylation."}
{"id": "PMID:187067", "title": "Effect of parathyroid hormone on renal tubular permeability.", "content": "The effect of parathyroid hormone (PTH) on renal tubular permeability has been studied utilizing micropuncture techniques in the rat kidney. After microinjection into superificial nephrons during control conditions, inulin (98.8 +/- 2.7%) and mannitol (97.2 +/- 2.4%) recovery from the experimental kidney was essentially complete. During intravenous infusion of PTH, inulin (99.3 +/- 2.9%) recovery was again complete. Mannitol recovery decreased signficantly after both early-proximal (84.7 +/- 5.8%, P less than 0.001) and late-proximal (89.7 +/- 2.8%, P less than 0.001) injections. There was no loss of either mannitol or inulin following distal tubular injection. Late-proximal TF/P inulin ratios during control conditions were 2.10 +/- 0.20 and decreased insignificantly to 1.99 +/- 0.21 during PTH infusion. Late-proximal TF/P mannitol rations were 2.09 +/- 0.21 during control periods and during PTH infusion decreased significantly to 1.78 +/- 0.19 (P less than 0.001). These results indicate that PTH induces a change in proximal tubular permeability to a usually impermeable nonelectrolyte, mannitol. The effects of PTH on proximal tubular transport could be partially explained by this alteration in permeability, which would increase passive backflux of actively transported species and decrease net transport while having no effect on active transport.", "contents": "Effect of parathyroid hormone on renal tubular permeability. The effect of parathyroid hormone (PTH) on renal tubular permeability has been studied utilizing micropuncture techniques in the rat kidney. After microinjection into superificial nephrons during control conditions, inulin (98.8 +/- 2.7%) and mannitol (97.2 +/- 2.4%) recovery from the experimental kidney was essentially complete. During intravenous infusion of PTH, inulin (99.3 +/- 2.9%) recovery was again complete. Mannitol recovery decreased signficantly after both early-proximal (84.7 +/- 5.8%, P less than 0.001) and late-proximal (89.7 +/- 2.8%, P less than 0.001) injections. There was no loss of either mannitol or inulin following distal tubular injection. Late-proximal TF/P inulin ratios during control conditions were 2.10 +/- 0.20 and decreased insignificantly to 1.99 +/- 0.21 during PTH infusion. Late-proximal TF/P mannitol rations were 2.09 +/- 0.21 during control periods and during PTH infusion decreased significantly to 1.78 +/- 0.19 (P less than 0.001). These results indicate that PTH induces a change in proximal tubular permeability to a usually impermeable nonelectrolyte, mannitol. The effects of PTH on proximal tubular transport could be partially explained by this alteration in permeability, which would increase passive backflux of actively transported species and decrease net transport while having no effect on active transport."}
{"id": "PMID:187068", "title": "Midbrain neuronal responses to local and spinal cord temperatures.", "content": "Water-perfused thermodes were implanted over the lumbothoracic spinal cord and unilaterally in the midbrain of urethan-anesthetized rabbits. Single-unit activities were recorded with steel microelectrodes from the thermosensitive neurons in the midbrain reticular formation (MRF), and the effects of heating and cooling of the spinal cord were studied. Of 38 cold-sensitive MRF neurons studied, 7 units decreased their firing rate upon elevation of spinal cord temperature (Tsc) and 3 units showed the opposite type of response to Tsc. The remaining 28 cold units were not affected by the changes in Tsc between 30 and 43 degrees C. Of 17 warm units, 3 units increased and one unit decreased the firing rate during spinal cord heating. These results suggest that the temperature signal arising from thermosensitive structures in the spinal cord may be transmitted to some of the locally thermosensitive neurons in the MRF.", "contents": "Midbrain neuronal responses to local and spinal cord temperatures. Water-perfused thermodes were implanted over the lumbothoracic spinal cord and unilaterally in the midbrain of urethan-anesthetized rabbits. Single-unit activities were recorded with steel microelectrodes from the thermosensitive neurons in the midbrain reticular formation (MRF), and the effects of heating and cooling of the spinal cord were studied. Of 38 cold-sensitive MRF neurons studied, 7 units decreased their firing rate upon elevation of spinal cord temperature (Tsc) and 3 units showed the opposite type of response to Tsc. The remaining 28 cold units were not affected by the changes in Tsc between 30 and 43 degrees C. Of 17 warm units, 3 units increased and one unit decreased the firing rate during spinal cord heating. These results suggest that the temperature signal arising from thermosensitive structures in the spinal cord may be transmitted to some of the locally thermosensitive neurons in the MRF."}
{"id": "PMID:187069", "title": "Simulation study of control of hepatic glycogen synthesis by glucose and insulin.", "content": "The plausibility of various hypotheses concerning the effects of glucow dynamic model of glucose metabolism in the liver. The model consisted of six compartments representing extracellular glucose, and intracellular glucose, glucose 6-phosphate, glucose 1-phosphate, uridine diphosphate glucose, obtained from literature reports, the model predicted values of intermediates which were close to those reported for the liver, sampled from fasting animals. The model predicts that glucose can generate significant glycogen deposition by engendering the inhibition of glucose-6-phosphatase, but not by mass action, glycogen synthase activation, or phosphorylase deactivation. The model predicts that, although insulin can inhibit glucose production by lowering phosphorylase and gluconeogenesis, only an insulin-mediated induction of glucokinase can account for insulin's action to potentiate the effect of glucose alone on glycogen synthesis.", "contents": "Simulation study of control of hepatic glycogen synthesis by glucose and insulin. The plausibility of various hypotheses concerning the effects of glucow dynamic model of glucose metabolism in the liver. The model consisted of six compartments representing extracellular glucose, and intracellular glucose, glucose 6-phosphate, glucose 1-phosphate, uridine diphosphate glucose, obtained from literature reports, the model predicted values of intermediates which were close to those reported for the liver, sampled from fasting animals. The model predicts that glucose can generate significant glycogen deposition by engendering the inhibition of glucose-6-phosphatase, but not by mass action, glycogen synthase activation, or phosphorylase deactivation. The model predicts that, although insulin can inhibit glucose production by lowering phosphorylase and gluconeogenesis, only an insulin-mediated induction of glucokinase can account for insulin's action to potentiate the effect of glucose alone on glycogen synthesis."}
{"id": "PMID:187071", "title": "Janeway Lecture: Pediatric cancer treatment: a model for oncology.", "content": "Advances in pediatric oncology are reviewed using Wilms's tumor as a model. From the period when Wilms's tumor was treated by surgery alone to the time when adjuvant radiation and chemotherapy enabled attainment of an 80% survival rate, true collaboration among surgeons, radiation therapists, and pediatricians has been the key to success. The National Wilms's Tumor Study seeks to further refine treatment so that survival rates are maximized with minimum morbidity. The lessons applicable to all in cancer management are that a team approach is essential, all forms of treatment should be weighed early, treatment should be skilled and vigorous from the beginning the biology and natural history of the tumor should be considered in treatment planning, and toxicities of all forms of treatment should be respected and ways designed for their reduction.", "contents": "Janeway Lecture: Pediatric cancer treatment: a model for oncology. Advances in pediatric oncology are reviewed using Wilms's tumor as a model. From the period when Wilms's tumor was treated by surgery alone to the time when adjuvant radiation and chemotherapy enabled attainment of an 80% survival rate, true collaboration among surgeons, radiation therapists, and pediatricians has been the key to success. The National Wilms's Tumor Study seeks to further refine treatment so that survival rates are maximized with minimum morbidity. The lessons applicable to all in cancer management are that a team approach is essential, all forms of treatment should be weighed early, treatment should be skilled and vigorous from the beginning the biology and natural history of the tumor should be considered in treatment planning, and toxicities of all forms of treatment should be respected and ways designed for their reduction."}
{"id": "PMID:187072", "title": "Cryoultramicroscopy of lower vertebrate retina.", "content": "Cryoultramicroscopy was carried out in the retina of lower vertebrates. Myeloid bodies of the pigment epithelium of turtles and synaptic vesicles and ribbons of frogs were stained negatively. Numerous altered, shaped, dense bodies, containing granular and myelinlike matrices, were found in the retinal pigment epithelium of turtle, and were thought to be lysosome. The advantages and disadvantages of this method are discussed.", "contents": "Cryoultramicroscopy of lower vertebrate retina. Cryoultramicroscopy was carried out in the retina of lower vertebrates. Myeloid bodies of the pigment epithelium of turtles and synaptic vesicles and ribbons of frogs were stained negatively. Numerous altered, shaped, dense bodies, containing granular and myelinlike matrices, were found in the retinal pigment epithelium of turtle, and were thought to be lysosome. The advantages and disadvantages of this method are discussed."}
{"id": "PMID:187073", "title": "[Ultrastructural aspects of chloroquin-keratopathy (author's transl)].", "content": "This reports deals with ultrastructural findings in chloroquin-keratopathy on the basis of three cases. Cytoplasmic inclusions are found in the corneal epithelium, alternately in the form of lamellar bodies, dense bodies, or as vacuoles with a variable content. Similar results are reported in the literature with other drugs and permit the conclusion that a pathologic mechanism depending on the amphiphilic character of these substances is involved. Thus they are able to undergo reactions with phosphilipids, disturbing the normal phosphilipid catabolism and leading to a drug-induced phospholipidosis.", "contents": "[Ultrastructural aspects of chloroquin-keratopathy (author's transl)]. This reports deals with ultrastructural findings in chloroquin-keratopathy on the basis of three cases. Cytoplasmic inclusions are found in the corneal epithelium, alternately in the form of lamellar bodies, dense bodies, or as vacuoles with a variable content. Similar results are reported in the literature with other drugs and permit the conclusion that a pathologic mechanism depending on the amphiphilic character of these substances is involved. Thus they are able to undergo reactions with phosphilipids, disturbing the normal phosphilipid catabolism and leading to a drug-induced phospholipidosis."}
{"id": "PMID:187086", "title": "Hormones and hormonal target cells in the testis.", "content": "Studies over the last few years have greatly increased our knowledge about target cells for sex hormones and gonadotropins in the testis. A diagram illustrating our present state of knowledge is given in Fig. 1. LH is the principle stimulus of testosterone secretion by the Leydig cells. Direct effects of estrogens and androgens on these cells might modulate the response to LH. Androgens are apparently influencing the differentiation and the contractility of peritubular cells. FSH is the principle stimulus for Sertoli cell secretory function before puberty, although androgens are acting synergistically with FSH. After puberty, androgens alone are capable of maintaining on optimal secretory function of the Sertoli cells. In addition to normal secretory activity of the Sertoli cells, direct stimulation of the germ cells by androgens is needed in order maintain spermatogenesis.", "contents": "Hormones and hormonal target cells in the testis. Studies over the last few years have greatly increased our knowledge about target cells for sex hormones and gonadotropins in the testis. A diagram illustrating our present state of knowledge is given in Fig. 1. LH is the principle stimulus of testosterone secretion by the Leydig cells. Direct effects of estrogens and androgens on these cells might modulate the response to LH. Androgens are apparently influencing the differentiation and the contractility of peritubular cells. FSH is the principle stimulus for Sertoli cell secretory function before puberty, although androgens are acting synergistically with FSH. After puberty, androgens alone are capable of maintaining on optimal secretory function of the Sertoli cells. In addition to normal secretory activity of the Sertoli cells, direct stimulation of the germ cells by androgens is needed in order maintain spermatogenesis."}
{"id": "PMID:187087", "title": "Isolation and characterization of a virus associated with progressive pneumonia (maedi) of sheep.", "content": "A virus with growth and morphologic characteristics of progressive pneumonia (maedi-visna) virus was isolated from the lungs of sheep with typical clinical and postmortem changes of chronic progressive pneumonia. The virus grew slowly in cultures of embryonic ovine lung cells, causing syncytial formation and degeneration. Syncytia developed much slower and involved fewer cells than reported for other similar viruses isolated from sheep. As seen with the electron microscope, the virus reproduced by budding from cell surfaces. Two types of virions were seen-a large particle (120 to 140 nm) with an electron-lucent center and dense laminated outer rim, and a small particle (80 to 110 nm) with an electron-dense core surrounded by a single membrane. Viral structures and fragments similar to the large extracellular particles were seen in the cytoplasm of a few cells. These characteristics are reported for other viruses isolated from sheep with progressive pneumonia.", "contents": "Isolation and characterization of a virus associated with progressive pneumonia (maedi) of sheep. A virus with growth and morphologic characteristics of progressive pneumonia (maedi-visna) virus was isolated from the lungs of sheep with typical clinical and postmortem changes of chronic progressive pneumonia. The virus grew slowly in cultures of embryonic ovine lung cells, causing syncytial formation and degeneration. Syncytia developed much slower and involved fewer cells than reported for other similar viruses isolated from sheep. As seen with the electron microscope, the virus reproduced by budding from cell surfaces. Two types of virions were seen-a large particle (120 to 140 nm) with an electron-lucent center and dense laminated outer rim, and a small particle (80 to 110 nm) with an electron-dense core surrounded by a single membrane. Viral structures and fragments similar to the large extracellular particles were seen in the cytoplasm of a few cells. These characteristics are reported for other viruses isolated from sheep with progressive pneumonia."}
{"id": "PMID:187088", "title": "Vaccination of newborn pigs with an attenuated strain of transmissible gastroenteritis virus.", "content": "Clinical signs of transmissible gastroenteritis were not observed in newborn pigs orally inoculated with the high-passaged vaccinal transmissible gastroenteritis virus (TO-163 strain). Vaccinal viral multiplication in digestive tract of newborn pigs fed colostrum before inoculation and kept at 21 to 22 C was diminished, but was not diminished in those fed colostrum and kept at 10 to 11 C. Other groups of newborn pigs inoculated with the attenuated vaccinal virus and kept at 18 to 22 C or at 31 to 34 C were challenge exposed with virulent intestinal virus on the 1st, 2nd, . . ., or 6th postinoculation (PI) days. In the groups kept at 18 to 22 C, 2 of 7 inoculated pigs challenge exposed with virulent virus on the 3rd PI day, 4 of 7 pigs exposed on the 4th PI day, and all of the pigs exposed on and after the 5th PI day survived the exposure. In the groups kept at 18 to 22 C, the attenuated vaccinal virus was distributed mainly in the respiratory organs and lymphatic tissues. On the contrary, in the groups kept at 31 to 34 C, all of the pigs died in 2 to 5 days after challenge exposure, and the attenuated vaccinal virus was scarcely detected in any of the pigs.", "contents": "Vaccination of newborn pigs with an attenuated strain of transmissible gastroenteritis virus. Clinical signs of transmissible gastroenteritis were not observed in newborn pigs orally inoculated with the high-passaged vaccinal transmissible gastroenteritis virus (TO-163 strain). Vaccinal viral multiplication in digestive tract of newborn pigs fed colostrum before inoculation and kept at 21 to 22 C was diminished, but was not diminished in those fed colostrum and kept at 10 to 11 C. Other groups of newborn pigs inoculated with the attenuated vaccinal virus and kept at 18 to 22 C or at 31 to 34 C were challenge exposed with virulent intestinal virus on the 1st, 2nd, . . ., or 6th postinoculation (PI) days. In the groups kept at 18 to 22 C, 2 of 7 inoculated pigs challenge exposed with virulent virus on the 3rd PI day, 4 of 7 pigs exposed on the 4th PI day, and all of the pigs exposed on and after the 5th PI day survived the exposure. In the groups kept at 18 to 22 C, the attenuated vaccinal virus was distributed mainly in the respiratory organs and lymphatic tissues. On the contrary, in the groups kept at 31 to 34 C, all of the pigs died in 2 to 5 days after challenge exposure, and the attenuated vaccinal virus was scarcely detected in any of the pigs."}
{"id": "PMID:187089", "title": "Leukocyte-aggregation assay for transmissible gastroenteritis of swine.", "content": "An in vitro leukocyte-aggregation assay was developed to detect the exposure of swine to transmissible gastroenteritis virus. Leukocytes in heparinized blood samples aggregated when mixed with test antigen prepared from transmissible gastroenteritis-infected swine testicle cell cultures. Twenty-two of 23 swine exposed 3 days or more were positive or suspects in the assay; 6 nonexposed swine were negative. Aggregation was shown as early as 3 days postexposure in 1 sow and persisted for as long as 14 months in another. Persistence of the assay was proved by repeated evaluations on 2 experimentally exposed swine.", "contents": "Leukocyte-aggregation assay for transmissible gastroenteritis of swine. An in vitro leukocyte-aggregation assay was developed to detect the exposure of swine to transmissible gastroenteritis virus. Leukocytes in heparinized blood samples aggregated when mixed with test antigen prepared from transmissible gastroenteritis-infected swine testicle cell cultures. Twenty-two of 23 swine exposed 3 days or more were positive or suspects in the assay; 6 nonexposed swine were negative. Aggregation was shown as early as 3 days postexposure in 1 sow and persisted for as long as 14 months in another. Persistence of the assay was proved by repeated evaluations on 2 experimentally exposed swine."}
{"id": "PMID:187090", "title": "Effects of metyrapone and ACTH on intestinal absorption of immunoreactive bovine IgG in cesarean-derived pigs.", "content": "Newborn cesarean-derived pigs were injected with 5.0 mg of metyrapone/kg, or 1 USP U of ACTH/kg, or the vehicle 1.0 ml of 44 mM sodium tartrate and 88 mM NaCl soon after delivery (0 hour) and again 4, 8, and 12 hours later. Beginning at 2 hours, each pig in the 3 groups was given 40 ml of pooled bovine colostrum/kg by stomach tube every 8 hours for the duration of the experiment. Four hours after each feeding, pigs were killed; plasma and serum were collected and assayed for cortisol and bovine immunoglobulin (IgG), respectively. Some nonfed, nontreated pigs were killed at 0 hour also. Metyrapone significantly decreased plasma cortisol (hydrocortisone) concentrations at all times tested, whereas ACTH-treated pigs demonstrated a biphasic increase of plasma cortisol. Immunoreactive serum bovine IgG was not detected in nonfed, nontreated pigs. In vehicle-injected control pigs, bovine IgG was present in the serum at 6 hours; the concentration increases consistently to 22 hours, but not significantly thereafter. The concentration of bovine IgG in the serum of metyrapone-treated pigs also increased steadily before plateauing at 22 hours, but the values were significantly less than those of the controls at 14, 22, 30, and 38 hours. The concentration of bovine IgG in the serum of ACTH-treated pigs did not differ significantly from the control values at any of the times tested.", "contents": "Effects of metyrapone and ACTH on intestinal absorption of immunoreactive bovine IgG in cesarean-derived pigs. Newborn cesarean-derived pigs were injected with 5.0 mg of metyrapone/kg, or 1 USP U of ACTH/kg, or the vehicle 1.0 ml of 44 mM sodium tartrate and 88 mM NaCl soon after delivery (0 hour) and again 4, 8, and 12 hours later. Beginning at 2 hours, each pig in the 3 groups was given 40 ml of pooled bovine colostrum/kg by stomach tube every 8 hours for the duration of the experiment. Four hours after each feeding, pigs were killed; plasma and serum were collected and assayed for cortisol and bovine immunoglobulin (IgG), respectively. Some nonfed, nontreated pigs were killed at 0 hour also. Metyrapone significantly decreased plasma cortisol (hydrocortisone) concentrations at all times tested, whereas ACTH-treated pigs demonstrated a biphasic increase of plasma cortisol. Immunoreactive serum bovine IgG was not detected in nonfed, nontreated pigs. In vehicle-injected control pigs, bovine IgG was present in the serum at 6 hours; the concentration increases consistently to 22 hours, but not significantly thereafter. The concentration of bovine IgG in the serum of metyrapone-treated pigs also increased steadily before plateauing at 22 hours, but the values were significantly less than those of the controls at 14, 22, 30, and 38 hours. The concentration of bovine IgG in the serum of ACTH-treated pigs did not differ significantly from the control values at any of the times tested."}
{"id": "PMID:187091", "title": "Scanning electron, light, and immunofluorescent microscopy of coronaviral enteritis of turkeys (Bluecomb).", "content": "Intestinal sections from both experimental and field cases of turkey coronaviral enteritis (TCE) were examined by scanning electron microscopy and light microscopy through 10 days after inoculation and by a direct fluorescent antibody test for TCE through 12 days. Serums were collected for an indirect fluorescent antibody test for TCE through 160 days after inoculation. Lesions observed with the scanning electron microscopy were catarrhal enteritis with hemorrhage per diapedesis, epithelial desquamation, and villous atrophy which developed and regressed within 6 days after inoculation. Light microscopy demonstrated similar lesions, except that villus-to-crypt ratios remained depressed 10 days. The direct fluorescent antibody test demonstrated the presence of coronaviral antigen throughout the sampling period, and serum antibodies to TCE were present until at least 160 days, when the experiment was terminated.", "contents": "Scanning electron, light, and immunofluorescent microscopy of coronaviral enteritis of turkeys (Bluecomb). Intestinal sections from both experimental and field cases of turkey coronaviral enteritis (TCE) were examined by scanning electron microscopy and light microscopy through 10 days after inoculation and by a direct fluorescent antibody test for TCE through 12 days. Serums were collected for an indirect fluorescent antibody test for TCE through 160 days after inoculation. Lesions observed with the scanning electron microscopy were catarrhal enteritis with hemorrhage per diapedesis, epithelial desquamation, and villous atrophy which developed and regressed within 6 days after inoculation. Light microscopy demonstrated similar lesions, except that villus-to-crypt ratios remained depressed 10 days. The direct fluorescent antibody test demonstrated the presence of coronaviral antigen throughout the sampling period, and serum antibodies to TCE were present until at least 160 days, when the experiment was terminated."}
{"id": "PMID:187092", "title": "In vitro interferon production by bovine tissues: effects of hydrocortisone.", "content": "The effect of hydrocortisone on bovine interferon production in vitro was studied. Infectious bovine rhinotracheitis virus was used as an inducer. Interferon was assayed by the plaque-reduction method in bovine fetal kidney cultures, using vesicular stomatitis virus as challenge virus. Hydrocortisone decreased interferon production in bovine fetal spleen and peripheral blood leukocyte cultures. Hydrocortisone did not decrease interferon production by bovine alveolar macrophages, in 1 experiment. Properties of viral inhibitors were those of interferon.", "contents": "In vitro interferon production by bovine tissues: effects of hydrocortisone. The effect of hydrocortisone on bovine interferon production in vitro was studied. Infectious bovine rhinotracheitis virus was used as an inducer. Interferon was assayed by the plaque-reduction method in bovine fetal kidney cultures, using vesicular stomatitis virus as challenge virus. Hydrocortisone decreased interferon production in bovine fetal spleen and peripheral blood leukocyte cultures. Hydrocortisone did not decrease interferon production by bovine alveolar macrophages, in 1 experiment. Properties of viral inhibitors were those of interferon."}
{"id": "PMID:187093", "title": "In vitro interferon production by bovine tissues: induction with infectious bovine rhinotracheitis virus.", "content": "The interferon-inducing ability of infectious bovine rhinotracheitis (IBR) virus was determined in tissue cultures of bovine origin inoculated with untreated and ultraviolet (UV) irradiated IBR viruses. Interferon was assayed by the plaque-reduction method in bovine fetal kidney (BFK) cell cultures, using vesicular stomatitis virus as challenge virus. Highest interferon concentrations were produced by cultures of bovine fetal (BF) spleen cells and aveolar macrophage cultures derived from adult cattle. Moderate interferon concentrations were produced by peripheral blood leukocyte (PBL) suspension cultures from adult cattle with serum-neutralizing antibodies against IBR virus. Cultures of PBL from 1 cow without detectable serum-neutralizing antibodies against IBR virus did not produce detectable interferon in response to IBR virus. Cultures of PBL from cattle with or without detectable serum-neutralizing antibodies against IBR virus produced interferon when stimulated with phytohemagglutinin (PHA). Low levles of viral inhibitors were detected infrequently in monolayer cultures of BFK and BF nasal mucosa inoculated with UV-irradiated IBR virus and in BF tracheal organ cultures inoculated with untreated IBR virus. Interferon was not detected in fluids collected from IBR virus-exposed monolayer cultures of primary and secondary BF lung, secondary BF tracheal mucosa, secondary BF liver, secondary BF adrenal, and PBL in the 4th and 7th passages. The antiviral inhibitors from BF spleen, bovine alveolar macrophage, and PBL cultures induced with IBR virus, as well as inhibitors from PBL cultures induced with PHA, had the usual properties of interferon.", "contents": "In vitro interferon production by bovine tissues: induction with infectious bovine rhinotracheitis virus. The interferon-inducing ability of infectious bovine rhinotracheitis (IBR) virus was determined in tissue cultures of bovine origin inoculated with untreated and ultraviolet (UV) irradiated IBR viruses. Interferon was assayed by the plaque-reduction method in bovine fetal kidney (BFK) cell cultures, using vesicular stomatitis virus as challenge virus. Highest interferon concentrations were produced by cultures of bovine fetal (BF) spleen cells and aveolar macrophage cultures derived from adult cattle. Moderate interferon concentrations were produced by peripheral blood leukocyte (PBL) suspension cultures from adult cattle with serum-neutralizing antibodies against IBR virus. Cultures of PBL from 1 cow without detectable serum-neutralizing antibodies against IBR virus did not produce detectable interferon in response to IBR virus. Cultures of PBL from cattle with or without detectable serum-neutralizing antibodies against IBR virus produced interferon when stimulated with phytohemagglutinin (PHA). Low levles of viral inhibitors were detected infrequently in monolayer cultures of BFK and BF nasal mucosa inoculated with UV-irradiated IBR virus and in BF tracheal organ cultures inoculated with untreated IBR virus. Interferon was not detected in fluids collected from IBR virus-exposed monolayer cultures of primary and secondary BF lung, secondary BF tracheal mucosa, secondary BF liver, secondary BF adrenal, and PBL in the 4th and 7th passages. The antiviral inhibitors from BF spleen, bovine alveolar macrophage, and PBL cultures induced with IBR virus, as well as inhibitors from PBL cultures induced with PHA, had the usual properties of interferon."}
{"id": "PMID:187094", "title": "Hydrogen sulfide intoxication. A case report and discussion of treatment.", "content": "The toxicity of hydrogen sulfide is thought to be due primarily to reversible inactivation of the respiratory enzyme, cytochrome oxidase, with resultant inhibition of aerobic metabolism. A patient with severe hydrogen sulfide poisoning and consequent profound metabolic acidosis was treated successfully with nitrites and oxygen. The nitrite-induced methemoglobin, by competitively binding the toxic hydrosulfide anion until detoxified, presumably reactivated and protected cytochrome oxidase and therby aided the patient's recovery by enhancing aerobic metabolism. His rapid recovery adds clinical support to the efficacy of nitrite therapy in sulfide poisoning. Therefore, we recommend that severe cases of sulfide poisoning be treated with nitrite-induced methemoglobinemia in addition to vigorous supportive care.", "contents": "Hydrogen sulfide intoxication. A case report and discussion of treatment. The toxicity of hydrogen sulfide is thought to be due primarily to reversible inactivation of the respiratory enzyme, cytochrome oxidase, with resultant inhibition of aerobic metabolism. A patient with severe hydrogen sulfide poisoning and consequent profound metabolic acidosis was treated successfully with nitrites and oxygen. The nitrite-induced methemoglobin, by competitively binding the toxic hydrosulfide anion until detoxified, presumably reactivated and protected cytochrome oxidase and therby aided the patient's recovery by enhancing aerobic metabolism. His rapid recovery adds clinical support to the efficacy of nitrite therapy in sulfide poisoning. Therefore, we recommend that severe cases of sulfide poisoning be treated with nitrite-induced methemoglobinemia in addition to vigorous supportive care."}
{"id": "PMID:187095", "title": "Naloxone.", "content": "Narcotic analgesics and related drugs act as agonists on several receptors that are responsible for their effects on pain perception, mood and feeling state, and respiration, as well as other pharmacologic actions. Naloxone is the first discovered antagonist that is devoid of agonistic activity and appears to be a competitive antagonist at several receptors. The ability of naloxone to displace or prevent the binding of agonistic narcotics is partly responsible for its antagonistic effects. The ability of naloxone to rectify narcotic-depressed homeostats and precipitate abstinence is also related to its antagonistic activity. Certain cautions and principles apply in the use of naloxone in treating narcotic overdose, reversing surgical analgesia, and the treatment of neonates and children. Unapproved uses of naloxine include reversing the psychotomimetic effects of certain agonists-antagonists, terminating narcotic-induced convulsions and coma, reversing non-narcotic depression, diagnosing physical dependence, and treating narcotic addicts.", "contents": "Naloxone. Narcotic analgesics and related drugs act as agonists on several receptors that are responsible for their effects on pain perception, mood and feeling state, and respiration, as well as other pharmacologic actions. Naloxone is the first discovered antagonist that is devoid of agonistic activity and appears to be a competitive antagonist at several receptors. The ability of naloxone to displace or prevent the binding of agonistic narcotics is partly responsible for its antagonistic effects. The ability of naloxone to rectify narcotic-depressed homeostats and precipitate abstinence is also related to its antagonistic activity. Certain cautions and principles apply in the use of naloxone in treating narcotic overdose, reversing surgical analgesia, and the treatment of neonates and children. Unapproved uses of naloxine include reversing the psychotomimetic effects of certain agonists-antagonists, terminating narcotic-induced convulsions and coma, reversing non-narcotic depression, diagnosing physical dependence, and treating narcotic addicts."}
{"id": "PMID:187099", "title": "Immunotherapy with nonviable microbial components.", "content": "Structural components of microorganisms have been studied for immunopotentiating effect with the aid of transplantable (line 10) tumors in syngeneic guinea pigs. Microbial components were associated with oil droplets, suspended in Tween-saline, and injected intralesionally. BCG cell walls, given in this way, produced regression and cure of 50-60% of established tumors, as did viable BCG. Lipid extraction markedly reduced the tumor-regressing potency of cell walls, but P3, a trehalose mycolate present in the extract, restored full activity to the cell wall residue. P3 alone was nonsensitizing and had no antitumor activity, but it enhanced the latter property of various other microbial products. For example, the cure rates produced by cell walls of M. tuberculosis, M. bovis, M. phlei, or M. smegmatis were enhanced from 20-60% to as much as 90% by addition of P3. P3 also conferred antitumor activity on products from unrelated microbes, such as cell walls of E. coli, and in combination with endotoxins from rough Re mutant salmonellae, it produced cure rates of up to 93%. These results suggest that P3 is essential to the immunopotentiating activity of mycobacteria and that it may be broadly applicable in immunotherapy of cancer with microbial agents.", "contents": "Immunotherapy with nonviable microbial components. Structural components of microorganisms have been studied for immunopotentiating effect with the aid of transplantable (line 10) tumors in syngeneic guinea pigs. Microbial components were associated with oil droplets, suspended in Tween-saline, and injected intralesionally. BCG cell walls, given in this way, produced regression and cure of 50-60% of established tumors, as did viable BCG. Lipid extraction markedly reduced the tumor-regressing potency of cell walls, but P3, a trehalose mycolate present in the extract, restored full activity to the cell wall residue. P3 alone was nonsensitizing and had no antitumor activity, but it enhanced the latter property of various other microbial products. For example, the cure rates produced by cell walls of M. tuberculosis, M. bovis, M. phlei, or M. smegmatis were enhanced from 20-60% to as much as 90% by addition of P3. P3 also conferred antitumor activity on products from unrelated microbes, such as cell walls of E. coli, and in combination with endotoxins from rough Re mutant salmonellae, it produced cure rates of up to 93%. These results suggest that P3 is essential to the immunopotentiating activity of mycobacteria and that it may be broadly applicable in immunotherapy of cancer with microbial agents."}
{"id": "PMID:187096", "title": "[Carboyydrates localization on ultrathin sections of \"Brucella\" and \"Escherichia\" cells in smooth (S) and rough (R) phase (author's transl)].", "content": "Carbohydrates localization on ultrathin sections of Brucella abortus, melitensis and Excherichia coli cells has been studied by the periodic acid thiocarbohydrazide-silver proteinate (PATAg) and phosphotungstic acid (PTA) methods. Carbohydrates are mainly localized on the cell envelope of Brucella and Escherichia but there are several differences between these two bacteria. The differences are discussed and a Brucella polysaccharide envelope model is proposed. The PATAg method gives the same silver grain deposits on Brucella S and R and Escherichia S and R. The phosphotungstic acid method differenciates Brucella S and R cells by lack of contrast on the outer leaflet of the outer membrane of the latter, but does not differenciate E. coli S or R cells. The Brucella outer membrane contains less polysaccharides than that of E. coli. There is a seemingly symetric distribution of polysaccharide in the Brucella outer membrane as compared to an asymetric distribution in E. coli. The peptidoglycan of Brucella reacts strongly as compared with that of E. coli. The polysaccharides present a dispersed pattern in Brucella cytoplasm, whereas in E. coli they appear as dense, strongly reactive clusters very close to the cytoplasmic membrane.", "contents": "[Carboyydrates localization on ultrathin sections of \"Brucella\" and \"Escherichia\" cells in smooth (S) and rough (R) phase (author's transl)]. Carbohydrates localization on ultrathin sections of Brucella abortus, melitensis and Excherichia coli cells has been studied by the periodic acid thiocarbohydrazide-silver proteinate (PATAg) and phosphotungstic acid (PTA) methods. Carbohydrates are mainly localized on the cell envelope of Brucella and Escherichia but there are several differences between these two bacteria. The differences are discussed and a Brucella polysaccharide envelope model is proposed. The PATAg method gives the same silver grain deposits on Brucella S and R and Escherichia S and R. The phosphotungstic acid method differenciates Brucella S and R cells by lack of contrast on the outer leaflet of the outer membrane of the latter, but does not differenciate E. coli S or R cells. The Brucella outer membrane contains less polysaccharides than that of E. coli. There is a seemingly symetric distribution of polysaccharide in the Brucella outer membrane as compared to an asymetric distribution in E. coli. The peptidoglycan of Brucella reacts strongly as compared with that of E. coli. The polysaccharides present a dispersed pattern in Brucella cytoplasm, whereas in E. coli they appear as dense, strongly reactive clusters very close to the cytoplasmic membrane."}
{"id": "PMID:187097", "title": "[Interactions of Shope papilloma virus with SV40 in adult domestic rabbit cell lines derived from normal skin or from Shope papilloma virus infected skin (author's transl)].", "content": "Three cell lines from adult domestic rabbit are infected with SV40: LP 17 and LP 45 derived from normal skin and LP 42 PS derived from skin infected for 24 h with Shope papilloma virus. The fibroblastic morphology of the cultures is not changed. SV40 is not recovered and T antigen is only detected in LP 42 PS cell line after 29 passages. To know if Shope papilloma virus facilitates penetration of SV40, cultures of LP 45 are first infected with Shope papilloma virus for 2 h and for 24 h, then superinfected with SV40. There is no cellular alteration, and T antigen induced by SV40 is only detected in cells pretreated for 24 h with Shope papilloma virus, after 20 passages. When cultures LP 45 are  infected with Shope papilloma virus neutralized with a high titer antiserum and superinfected with SV40, T antigen is not detected. Superinfected cells containing specific SV40 T antigen do not induce tumors either in new born hamsters or in rabbits but they are able to grow in colonies in soft agar. LP 42 PS cell line and LP 45 cells infected with Shope papilloma virus for 24 h containe Shope papilloma virus genome which is able to modify the permissivity of rabbit cells to SV40.", "contents": "[Interactions of Shope papilloma virus with SV40 in adult domestic rabbit cell lines derived from normal skin or from Shope papilloma virus infected skin (author's transl)]. Three cell lines from adult domestic rabbit are infected with SV40: LP 17 and LP 45 derived from normal skin and LP 42 PS derived from skin infected for 24 h with Shope papilloma virus. The fibroblastic morphology of the cultures is not changed. SV40 is not recovered and T antigen is only detected in LP 42 PS cell line after 29 passages. To know if Shope papilloma virus facilitates penetration of SV40, cultures of LP 45 are first infected with Shope papilloma virus for 2 h and for 24 h, then superinfected with SV40. There is no cellular alteration, and T antigen induced by SV40 is only detected in cells pretreated for 24 h with Shope papilloma virus, after 20 passages. When cultures LP 45 are  infected with Shope papilloma virus neutralized with a high titer antiserum and superinfected with SV40, T antigen is not detected. Superinfected cells containing specific SV40 T antigen do not induce tumors either in new born hamsters or in rabbits but they are able to grow in colonies in soft agar. LP 42 PS cell line and LP 45 cells infected with Shope papilloma virus for 24 h containe Shope papilloma virus genome which is able to modify the permissivity of rabbit cells to SV40."}
{"id": "PMID:187110", "title": "[Alkyl sulfates and alkyl aryl sulfonates as inhibitors of penicillinase].", "content": "The kinetics of inhibition of penicillinase of Bac. licheniformis 749/c by various alkyl-sulphates (with a long hydrocarbon chain from C8 to C16), n-toluolsulphoacid and alkylbenzol-sulphonate (R-C12--C16) was studied. The inhibition rate increased with elongation of the alkyl radical and rising of the inhibitor concentraiton. This means that the determining factor in inhibition process was hydrophobic interaction of the alkyl chains and not the electrostatic interaction with the enzyme. In-vitro experiments with penicillinase-producing strains of staphylococcus showed that non-bactericidal concentrations of the alkylsulphates and alkylben zolsulphonates increased the effect of benzylpenicillin, ampicillin and methicillin. The highest increase in the antibiotic activity, as well as in the enzyme inhibition was observed with respect to the compound with the hydrocarbon chain fron C12 to C16. The increase in the activity of methicillin against the staphylococcal strains resistant simultaneously to benzylpenicillin, ampicillin and methicillin was indicative of possible using of the above surface active substances as inhibitors of the realization process of various mechanisms of penicillin resistance.", "contents": "[Alkyl sulfates and alkyl aryl sulfonates as inhibitors of penicillinase]. The kinetics of inhibition of penicillinase of Bac. licheniformis 749/c by various alkyl-sulphates (with a long hydrocarbon chain from C8 to C16), n-toluolsulphoacid and alkylbenzol-sulphonate (R-C12--C16) was studied. The inhibition rate increased with elongation of the alkyl radical and rising of the inhibitor concentraiton. This means that the determining factor in inhibition process was hydrophobic interaction of the alkyl chains and not the electrostatic interaction with the enzyme. In-vitro experiments with penicillinase-producing strains of staphylococcus showed that non-bactericidal concentrations of the alkylsulphates and alkylben zolsulphonates increased the effect of benzylpenicillin, ampicillin and methicillin. The highest increase in the antibiotic activity, as well as in the enzyme inhibition was observed with respect to the compound with the hydrocarbon chain fron C12 to C16. The increase in the activity of methicillin against the staphylococcal strains resistant simultaneously to benzylpenicillin, ampicillin and methicillin was indicative of possible using of the above surface active substances as inhibitors of the realization process of various mechanisms of penicillin resistance."}
{"id": "PMID:187111", "title": "[Effect of antibiotic action on the submicroscopic structure of Salmonella. The action of monomycin on S. typhi].", "content": "The effect of subinhibitory concentrations of monomycin on the submicroscopic structures of 2 strains of S. typhi, 5 and 799 was studied. It was shown that formation of filamentoue forms, separation of the cell wall, thinning out of the cytoplasm granular component, increasing of the size of the matter with low electron optic density of fine granular structure were common in the cell response of both strains. Formation of vacuoli containing the thinned out granular component, filterable elements and complex membrane structures followed by their liberation into the medium and formation of the forms devoid of the cell walls was a characteristic peculiar property of the cell response in strain 799. The cells of strain 5 were characterized by formation of large granular osmiefilic matters and their excretion from the cells.", "contents": "[Effect of antibiotic action on the submicroscopic structure of Salmonella. The action of monomycin on S. typhi]. The effect of subinhibitory concentrations of monomycin on the submicroscopic structures of 2 strains of S. typhi, 5 and 799 was studied. It was shown that formation of filamentoue forms, separation of the cell wall, thinning out of the cytoplasm granular component, increasing of the size of the matter with low electron optic density of fine granular structure were common in the cell response of both strains. Formation of vacuoli containing the thinned out granular component, filterable elements and complex membrane structures followed by their liberation into the medium and formation of the forms devoid of the cell walls was a characteristic peculiar property of the cell response in strain 799. The cells of strain 5 were characterized by formation of large granular osmiefilic matters and their excretion from the cells."}
{"id": "PMID:187113", "title": "[Experimental study of the organotropic side-effect properties of polymyxin B].", "content": "Toxicity of Soviet polymyxin B and its effect on the central peripheral nervous system, blood circulation, respiration, smooth muscles, functional liver and kidney state, growth and development of young animals, the picture of the peripheral blood were studied in acute and chronic experiments on various species of animals. It was found that polymyxin B had a suppressing effect on the peripheral n-cholinoreactive systems of the neuromuscle synapses of the skeletal muscles and ganglia of the sympathic and parasympathic innervation and deprimizing effect on the central nervous system. Caffeine, adrenaline and calcium chloride proved to be the antagonists of the neurotoxic effects of polymyxin B. The chronic experiments revealed that polymyxin B induced disorders in the kidney function and morphological changes in the glomeruli after its repeated administration. No significant effect of polymyxin B on the growth and development of the young animals, the functional state of the liver and the picture of the peripheral blood was observed when the drug was used in doses corresponding to the therapeutic ones in clinics.", "contents": "[Experimental study of the organotropic side-effect properties of polymyxin B]. Toxicity of Soviet polymyxin B and its effect on the central peripheral nervous system, blood circulation, respiration, smooth muscles, functional liver and kidney state, growth and development of young animals, the picture of the peripheral blood were studied in acute and chronic experiments on various species of animals. It was found that polymyxin B had a suppressing effect on the peripheral n-cholinoreactive systems of the neuromuscle synapses of the skeletal muscles and ganglia of the sympathic and parasympathic innervation and deprimizing effect on the central nervous system. Caffeine, adrenaline and calcium chloride proved to be the antagonists of the neurotoxic effects of polymyxin B. The chronic experiments revealed that polymyxin B induced disorders in the kidney function and morphological changes in the glomeruli after its repeated administration. No significant effect of polymyxin B on the growth and development of the young animals, the functional state of the liver and the picture of the peripheral blood was observed when the drug was used in doses corresponding to the therapeutic ones in clinics."}
{"id": "PMID:187114", "title": "Effect of sodium nitrite inhibition on intracellular thiol groups and on the activity of certain glycolytic enzymes in Clostridium perfringens.", "content": "Activities of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) (GAP-DH) and aldolase (EC 4.1.2.13) in cells of Clostridium perfringens that had been inhibited with sodium nitrite were investigated. A complete loss in GAP-DH activity and a 67% decrease in aldolase activity were observed when growth of C. perfringens was inhibited. There was also a 91% decrease in the concentration of free sulfhydryl groups of soluble cellular components. Dithiothreitol restored some activity to inactive GAP-DH from sodium nitrite-inhibited cells, indicating that a loss of reduced sulfhydryl groups was involved in the inactivation of the enzyme. The evidence presented suggests that sodium nitrite inhibition of C. perfringens may involve an interaction of sodium nitrite as nitrous acid with sulfhydryl-containing constituents of the bacterial cell.", "contents": "Effect of sodium nitrite inhibition on intracellular thiol groups and on the activity of certain glycolytic enzymes in Clostridium perfringens. Activities of glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) (GAP-DH) and aldolase (EC 4.1.2.13) in cells of Clostridium perfringens that had been inhibited with sodium nitrite were investigated. A complete loss in GAP-DH activity and a 67% decrease in aldolase activity were observed when growth of C. perfringens was inhibited. There was also a 91% decrease in the concentration of free sulfhydryl groups of soluble cellular components. Dithiothreitol restored some activity to inactive GAP-DH from sodium nitrite-inhibited cells, indicating that a loss of reduced sulfhydryl groups was involved in the inactivation of the enzyme. The evidence presented suggests that sodium nitrite inhibition of C. perfringens may involve an interaction of sodium nitrite as nitrous acid with sulfhydryl-containing constituents of the bacterial cell."}
{"id": "PMID:187115", "title": "Concentration of viruses from large volumes of tap water using pleated membrane filters.", "content": "A method is described for the efficient concentration of viruses from large volumes of tap water in relatively short time periods. Virus in acidified tap water in the presence of aluminum chloride is adsorbed to a 10-inch (ca. 25.4 cm) fiberglass depth cartridge and a 10-inch pleated epoxy-fiberglass filter in series at flow rates of up to 37.8 liters/min (10 gallons/min). This filter series is capable of efficiently adsorbing virus from greater than 19,000 liters (5,000 gallons) of treated tap water. Adsorbed viruses are eluted from the filters with glycine buffer (pH 10.5) and the eluate is reconcentrated using an aluminum flocculation process. Viruses are eluted from the aluminum floc with glycine buffer (pH 11.5). Using this procedure, viruses in 1,900 liters (500 gallons) of tap water can be concentrated 100,000-fold in 3 h with an average recovery of 40 to 50%.", "contents": "Concentration of viruses from large volumes of tap water using pleated membrane filters. A method is described for the efficient concentration of viruses from large volumes of tap water in relatively short time periods. Virus in acidified tap water in the presence of aluminum chloride is adsorbed to a 10-inch (ca. 25.4 cm) fiberglass depth cartridge and a 10-inch pleated epoxy-fiberglass filter in series at flow rates of up to 37.8 liters/min (10 gallons/min). This filter series is capable of efficiently adsorbing virus from greater than 19,000 liters (5,000 gallons) of treated tap water. Adsorbed viruses are eluted from the filters with glycine buffer (pH 10.5) and the eluate is reconcentrated using an aluminum flocculation process. Viruses are eluted from the aluminum floc with glycine buffer (pH 11.5). Using this procedure, viruses in 1,900 liters (500 gallons) of tap water can be concentrated 100,000-fold in 3 h with an average recovery of 40 to 50%."}
{"id": "PMID:187116", "title": "Detection of virus in water: sensitivity of the tentative standard method for drinking water.", "content": "The sensitivity of several microporous virus-adsorbent media for reliably detecting low levels of poliovirus from 380 and 1,900 liters of drinking water by use of the tentative standard method was investigated. The virus-adsorbent media tested were (i) nitrocellulose membrane filters, (ii) epoxy-fiber glass-asbestos filters, (iii) yarn-wound fiber glass depth filters, and (iv) epoxy-fiber glass filter tubes. Virus was adsorbed to the filter media at pH 3.5 and eluted with glycine buffer, pH 11.5. The results from 44 samples demonstrated that poliovirus was detected with a 95% reliability at mean virus input levels of 3 to 7 plaque-forming units/380 liters when 1,900 liters of water was sampled. At mean virus input levels of less than 1 to 2 plaque-forming units/380 liters, the detection reliability was 66% in 76 samples when 1,900 liters of water was sampled. No significant difference in virus detection sensitivity was observed among the various virus adsorbent media tested. Overall virus recovery efficiency ranged from 28 to 42%, with a grand average of 35%. Members of the coxsackievirus groups A and B, echovirus, and adenovirus were also detected when 380 and 1,900 liters of water were sampled. These experimental observations attest to the sensitivity of the tentative standard method for detecting low levels of virus in large volumes of drinking water.", "contents": "Detection of virus in water: sensitivity of the tentative standard method for drinking water. The sensitivity of several microporous virus-adsorbent media for reliably detecting low levels of poliovirus from 380 and 1,900 liters of drinking water by use of the tentative standard method was investigated. The virus-adsorbent media tested were (i) nitrocellulose membrane filters, (ii) epoxy-fiber glass-asbestos filters, (iii) yarn-wound fiber glass depth filters, and (iv) epoxy-fiber glass filter tubes. Virus was adsorbed to the filter media at pH 3.5 and eluted with glycine buffer, pH 11.5. The results from 44 samples demonstrated that poliovirus was detected with a 95% reliability at mean virus input levels of 3 to 7 plaque-forming units/380 liters when 1,900 liters of water was sampled. At mean virus input levels of less than 1 to 2 plaque-forming units/380 liters, the detection reliability was 66% in 76 samples when 1,900 liters of water was sampled. No significant difference in virus detection sensitivity was observed among the various virus adsorbent media tested. Overall virus recovery efficiency ranged from 28 to 42%, with a grand average of 35%. Members of the coxsackievirus groups A and B, echovirus, and adenovirus were also detected when 380 and 1,900 liters of water were sampled. These experimental observations attest to the sensitivity of the tentative standard method for detecting low levels of virus in large volumes of drinking water."}
{"id": "PMID:187117", "title": "Fermentation of glucose-1-phosphate: a screening test for fermentative Bacteroides species.", "content": "Of 1,504 strains of anaerobic bacteria tested, 544 produced acid from glucose-1-phosphate. Of these, 535 were fermentative strains of Bacteroides; only three fermentative Bacteroides strains were negative. The reaction may be useful for determination of the number of Bacteroides species present in colon content and feces.", "contents": "Fermentation of glucose-1-phosphate: a screening test for fermentative Bacteroides species. Of 1,504 strains of anaerobic bacteria tested, 544 produced acid from glucose-1-phosphate. Of these, 535 were fermentative strains of Bacteroides; only three fermentative Bacteroides strains were negative. The reaction may be useful for determination of the number of Bacteroides species present in colon content and feces."}
{"id": "PMID:187127", "title": "Viral infection in wheezy bronchitis and asthma in children.", "content": "Virus isolation was attempted on 267 out of 360 patients with wheezy bronchitis or asthma admitted to hospital during a 3-year period. Viruses were isolated on 39 occasions, the most common being respiratory syncytial virus and rhinovirus. The peak months for virus isolation were February and August. Virus isolation was significantly more common in readmissions than in first admissions (P less than 0-01). Viruses were isolated in both sexes throughout childhood and though the admission rate fell with increasing age, the isolation rate was unaffected. The possible significance of viral infection as a cause of acute attacks of wheezing in children is discussed.", "contents": "Viral infection in wheezy bronchitis and asthma in children. Virus isolation was attempted on 267 out of 360 patients with wheezy bronchitis or asthma admitted to hospital during a 3-year period. Viruses were isolated on 39 occasions, the most common being respiratory syncytial virus and rhinovirus. The peak months for virus isolation were February and August. Virus isolation was significantly more common in readmissions than in first admissions (P less than 0-01). Viruses were isolated in both sexes throughout childhood and though the admission rate fell with increasing age, the isolation rate was unaffected. The possible significance of viral infection as a cause of acute attacks of wheezing in children is discussed."}
{"id": "PMID:187128", "title": "Restoration of virulence to rat of axenically grown Entamoeba histolytica by cholesterol and hamster liver passage.", "content": "A virulent strain of Entamoeba histolytica (NIH-200) from a symptomatic human case, cultured in vitro for more than three years, was unable to infect rat caecum or hamster liver. When grown with a mixed bacterial flora, it infected rat caecum but did not produce ulceration. After passaging amoebae growing with bacteria in hamster liver, amoebic hepatic lesions were regularly produced. The amoebae from liver lesions produced ulceration in the caeca of rats. Expoxure to cholesterol of amoebae growing with bacteria or feeding rats orally with cholesterol and injecting these amoebae along with bacteria also led to the production of ulcers in rats. Thus virulent amoebae which have been cultured in vitro for a long time become attenuated but their virulence can be revived.", "contents": "Restoration of virulence to rat of axenically grown Entamoeba histolytica by cholesterol and hamster liver passage. A virulent strain of Entamoeba histolytica (NIH-200) from a symptomatic human case, cultured in vitro for more than three years, was unable to infect rat caecum or hamster liver. When grown with a mixed bacterial flora, it infected rat caecum but did not produce ulceration. After passaging amoebae growing with bacteria in hamster liver, amoebic hepatic lesions were regularly produced. The amoebae from liver lesions produced ulceration in the caeca of rats. Expoxure to cholesterol of amoebae growing with bacteria or feeding rats orally with cholesterol and injecting these amoebae along with bacteria also led to the production of ulcers in rats. Thus virulent amoebae which have been cultured in vitro for a long time become attenuated but their virulence can be revived."}
{"id": "PMID:187130", "title": "Interactions of chlorphenesin and divalent metal ions with phosphodiesterase.", "content": "Chlorphenesin inhibition of the hydrolysis of cyclic AMP by guinea-pig lung phosphodiesterase was reversed by the addition of exogenous magnesium ions. Chlorphenesin and theophylline inhibition of this enzyme was shown to be noncompetitive when the substrate concentration was low. Kinetic studies of the inhibition of beef heart phosphodiesterase by chlorphenesin and theophylline indicated that the substrate concentration was a factor in determining whether inhibition was competitive or noncompetitive. Calcium, cobalt and copper ions were inhibitory to guinea-pig lung phosphodiesterase. The inhibition due to chlorphenesin was partially reversed by low (40 mM or less) concentrations of barium ions; high concentrations of barium ions, or manganese ions, were inhibitory. The concentration of the divalent cation did not affect the type of inhibition that was observed.", "contents": "Interactions of chlorphenesin and divalent metal ions with phosphodiesterase. Chlorphenesin inhibition of the hydrolysis of cyclic AMP by guinea-pig lung phosphodiesterase was reversed by the addition of exogenous magnesium ions. Chlorphenesin and theophylline inhibition of this enzyme was shown to be noncompetitive when the substrate concentration was low. Kinetic studies of the inhibition of beef heart phosphodiesterase by chlorphenesin and theophylline indicated that the substrate concentration was a factor in determining whether inhibition was competitive or noncompetitive. Calcium, cobalt and copper ions were inhibitory to guinea-pig lung phosphodiesterase. The inhibition due to chlorphenesin was partially reversed by low (40 mM or less) concentrations of barium ions; high concentrations of barium ions, or manganese ions, were inhibitory. The concentration of the divalent cation did not affect the type of inhibition that was observed."}
{"id": "PMID:187131", "title": "Effect of propranolol on the relationship between atrial systolic pressure and type A atrial receptor discharge in cats.", "content": "The responses of type A atrial receptors to graded infusions of saline and large doses of propranolol were examined in anesthetized cats. Infusion of saline raised the mean atrial pressure, but usually the amplitude of the atrial a wave was reduced. In general the receptor discharge was unaffected. Propranolol reduced the discharge from the control level when it was injected in doses no less than 4 mg/kg. Infusions of saline after propranolol resulted in an increase in the discharge and the increase was related to the amplitude and/or initial pressure of the a wave. In one case the discharge after propranolol was less than that when the atrium was widely slit open. It is concluded that at least part of the effect of the drug is due to a direct depression of the receptor rendering it less sensitive to the stretch provided by atrial contraction. The demonstration of a stimulus-response relationship between the a wave and the receptor discharge at low levels of activity suggests that under normal conditiions the receptor operates on a plateau of maximum activity, thus making a response to small changes in stimulus strength obscure.", "contents": "Effect of propranolol on the relationship between atrial systolic pressure and type A atrial receptor discharge in cats. The responses of type A atrial receptors to graded infusions of saline and large doses of propranolol were examined in anesthetized cats. Infusion of saline raised the mean atrial pressure, but usually the amplitude of the atrial a wave was reduced. In general the receptor discharge was unaffected. Propranolol reduced the discharge from the control level when it was injected in doses no less than 4 mg/kg. Infusions of saline after propranolol resulted in an increase in the discharge and the increase was related to the amplitude and/or initial pressure of the a wave. In one case the discharge after propranolol was less than that when the atrium was widely slit open. It is concluded that at least part of the effect of the drug is due to a direct depression of the receptor rendering it less sensitive to the stretch provided by atrial contraction. The demonstration of a stimulus-response relationship between the a wave and the receptor discharge at low levels of activity suggests that under normal conditiions the receptor operates on a plateau of maximum activity, thus making a response to small changes in stimulus strength obscure."}
{"id": "PMID:187132", "title": "Influence of adenosine, cAMP and db-cAMP on responses of the isolated terminal guinea-pig ileum to electrical stimulation.", "content": "Adenosine, cAMP and db-cAMP were found to inhibit nerve-mediated contractions of the terminal ileum elicited by electrical stimulation (ES). Responses to ES at 30 Hz, which are believed to be of adrenergic origin, were considerably more affected than the responses to ES at 3 Hz, which may be of purinergic orign. The following order of relative inhibitory potencies was established: adenosine greater than cAMP greater than db-cAMP. Adenosine, cAMP and db-cAMP did not affect the contractile responses of the preparation to histamine, potassium and noradrenaline. Therefore, the observed inhibition of nerve-mediated contractions was thought to be due to an action on presynaptic sites, i.e. on the neural network within the intestine. This action was antagonized by an increase in external calcium and by aminophylline, which is known to increase intracellular calcium. The present experiments suggests that the inhibitory action of adenosine, cAMP and db-cAMP results from a reduction of calcium fluxes across the neural membrane and to a subsequent reduction in the release of neurotransmitter(s). The inhibitory effect of cAMP appeared to be nonspecific and was presumably related to adenosine in its molecule.", "contents": "Influence of adenosine, cAMP and db-cAMP on responses of the isolated terminal guinea-pig ileum to electrical stimulation. Adenosine, cAMP and db-cAMP were found to inhibit nerve-mediated contractions of the terminal ileum elicited by electrical stimulation (ES). Responses to ES at 30 Hz, which are believed to be of adrenergic origin, were considerably more affected than the responses to ES at 3 Hz, which may be of purinergic orign. The following order of relative inhibitory potencies was established: adenosine greater than cAMP greater than db-cAMP. Adenosine, cAMP and db-cAMP did not affect the contractile responses of the preparation to histamine, potassium and noradrenaline. Therefore, the observed inhibition of nerve-mediated contractions was thought to be due to an action on presynaptic sites, i.e. on the neural network within the intestine. This action was antagonized by an increase in external calcium and by aminophylline, which is known to increase intracellular calcium. The present experiments suggests that the inhibitory action of adenosine, cAMP and db-cAMP results from a reduction of calcium fluxes across the neural membrane and to a subsequent reduction in the release of neurotransmitter(s). The inhibitory effect of cAMP appeared to be nonspecific and was presumably related to adenosine in its molecule."}
{"id": "PMID:187133", "title": "An alpha-adrenotypic study of the isolated rabbit kidney at normo- and hypothermia.", "content": "Rabbit kidneys were isolated and perfused at 37degrees and 25degrees C with a balanced salt solution and the effects of an alpha agonist and antagonist were tested in several parameters. Perfusion pressure, resistance, perfusate and urine flow, creatinine and PAH clearance, and Na+ and K+ transport were among the parameters studied. At 25degrees C the vascular responses to norepinephrine (NOR) were potentiated in relation to 37 degrees C. Blockade of the reuptake by cocaine and depletion of catecholamines by reserpine was observed to promote a small potentiation of NOR effects on renal vessels as measured by perfusion pressure. This pharmacological treatment compromised kidney function especially after the first 40 min of perfusion, that is to say that after NOR infusion functional parameters were extremely low. During the infusion of NOR there was a decrease in GFR, urinary flow and CPAH, which was even more intense at 25 degrees C. It was concluded that alpha adrenergic receptors are more responsive at 25 degrees C than at 37 degrees C in kidney vascular receptors. There was no difference in regard to alpha blockade at either temperature tested.", "contents": "An alpha-adrenotypic study of the isolated rabbit kidney at normo- and hypothermia. Rabbit kidneys were isolated and perfused at 37degrees and 25degrees C with a balanced salt solution and the effects of an alpha agonist and antagonist were tested in several parameters. Perfusion pressure, resistance, perfusate and urine flow, creatinine and PAH clearance, and Na+ and K+ transport were among the parameters studied. At 25degrees C the vascular responses to norepinephrine (NOR) were potentiated in relation to 37 degrees C. Blockade of the reuptake by cocaine and depletion of catecholamines by reserpine was observed to promote a small potentiation of NOR effects on renal vessels as measured by perfusion pressure. This pharmacological treatment compromised kidney function especially after the first 40 min of perfusion, that is to say that after NOR infusion functional parameters were extremely low. During the infusion of NOR there was a decrease in GFR, urinary flow and CPAH, which was even more intense at 25 degrees C. It was concluded that alpha adrenergic receptors are more responsive at 25 degrees C than at 37 degrees C in kidney vascular receptors. There was no difference in regard to alpha blockade at either temperature tested."}
{"id": "PMID:187134", "title": "Different membrane mechanisms of action for tiemonium; a comparison with atropine and papaverine.", "content": "The effects of tiemonium on various membrane events preceding smooth muscle fibre contraction, have been studied in vitro. Classical molecular pharmacological models and methods were used: stimulation of muscarinic, histamine H1 and alpha-adrenergic receptors; induction of contraction by release of membrane phospholipid bound Ca2+ ions, or by intracytoplasmic influx of this cation in depolarized preparations. At each level of investigation, tiemonium was studied comparatively with two reference antispasmodics, atropine and papaverine. Like atropine, tiemonium competitively antagonizes cholinergic stimulation. It also interferes with the contracting effects of BaCl2, as does papaverine. In contrast to papverine, however, tiemonium shows an affinity for histamine H1-receptors, and does not affect alpha-adrenergic receptor stimulation. Tiemonium is therefore a novel antispasmodic which blocks the cholinergic receptor, but being less specific than atropine. This non-specific facet makes it almost as polyvalent as papaverine, in its general inhibition of spasmogenic substances, but its mechanism of action is very different. Whereas papaverine slows intracytoplasmic Ca2+ influx, tiemonium inhibits release, and thus availability, of the same ion. Tiemonium has a totally different mechanism of antispasmodic action from that other substances in the same pharmacological class. The marked competitive interference with acetylcholine and the very weak competitive antagonism of histamine are completed by a membrane stabilizing action. In particular, the latter reinforces the binding of calcium to membrane phospholipids. The absence of any interaction of tiemonium with noradrenaline is compatible with recent theories for noradrenaline's action, which evoke calcium exchanges in an intracytoplasmic compartment. Finally, the results raise the question of the pharmacological suitability of the term \"papaverine-like\" for describing non-specific antispasmodics.", "contents": "Different membrane mechanisms of action for tiemonium; a comparison with atropine and papaverine. The effects of tiemonium on various membrane events preceding smooth muscle fibre contraction, have been studied in vitro. Classical molecular pharmacological models and methods were used: stimulation of muscarinic, histamine H1 and alpha-adrenergic receptors; induction of contraction by release of membrane phospholipid bound Ca2+ ions, or by intracytoplasmic influx of this cation in depolarized preparations. At each level of investigation, tiemonium was studied comparatively with two reference antispasmodics, atropine and papaverine. Like atropine, tiemonium competitively antagonizes cholinergic stimulation. It also interferes with the contracting effects of BaCl2, as does papaverine. In contrast to papverine, however, tiemonium shows an affinity for histamine H1-receptors, and does not affect alpha-adrenergic receptor stimulation. Tiemonium is therefore a novel antispasmodic which blocks the cholinergic receptor, but being less specific than atropine. This non-specific facet makes it almost as polyvalent as papaverine, in its general inhibition of spasmogenic substances, but its mechanism of action is very different. Whereas papaverine slows intracytoplasmic Ca2+ influx, tiemonium inhibits release, and thus availability, of the same ion. Tiemonium has a totally different mechanism of antispasmodic action from that other substances in the same pharmacological class. The marked competitive interference with acetylcholine and the very weak competitive antagonism of histamine are completed by a membrane stabilizing action. In particular, the latter reinforces the binding of calcium to membrane phospholipids. The absence of any interaction of tiemonium with noradrenaline is compatible with recent theories for noradrenaline's action, which evoke calcium exchanges in an intracytoplasmic compartment. Finally, the results raise the question of the pharmacological suitability of the term \"papaverine-like\" for describing non-specific antispasmodics."}
{"id": "PMID:187135", "title": "[Digestive absorption, fixation and excretion of oral disulfiram in the rat].", "content": "Absorption, distribution and excretion of disulfiram and of one of its metabolites, diethyldithiocarbamate, were studied in rats orally treated with disulfiram (25 or 250 mg/kg). It was noted that this compound is absorbed in a proportion of 70-90 per cent of the administered dose but that diethyldithiocarbamate can appear already in the gut. After absorption, disulfiram and diethyldithiocarbamate impregnate specifically some tissues such as liver, kidney and muscle; blood and brain contain little or no disulfiram. The largest dose of disulfiram decreases fecal bolus and increases urinary volume favouring perhaps excretion of diethyldithiocarbamate.", "contents": "[Digestive absorption, fixation and excretion of oral disulfiram in the rat]. Absorption, distribution and excretion of disulfiram and of one of its metabolites, diethyldithiocarbamate, were studied in rats orally treated with disulfiram (25 or 250 mg/kg). It was noted that this compound is absorbed in a proportion of 70-90 per cent of the administered dose but that diethyldithiocarbamate can appear already in the gut. After absorption, disulfiram and diethyldithiocarbamate impregnate specifically some tissues such as liver, kidney and muscle; blood and brain contain little or no disulfiram. The largest dose of disulfiram decreases fecal bolus and increases urinary volume favouring perhaps excretion of diethyldithiocarbamate."}
{"id": "PMID:187136", "title": "Streptozocin-treated Verner-Morrison Syndrome: plasma vasoactive intestinal peptide and tumor responses.", "content": "A patient with watery diarrhea, hypokalemia, hypochlorhydria, and a non-beta islet cell carcinoma of the pancreas (Verner-Morrison syndrome) was found to have an elevated vasoactive intestinal peptide (VIP) concentration in the plasma as well as in the tumor. Treatment with streptozocin resulted in a dramatic subjective and objective tumor response in this patient. Plasma VIP concentration fell into the normal range after four courses of treatment, diarrhea ceased after the third course of therapy, and measurable tumor mass markedly decreased during that same period of time. The patient remains in clinical remission with no evidence of tumor regrowth 18 months after the beginning of treatment. In this patient, plasma VIP measurements were an excellent marker of tumor activity and correlated well with objective disease measurements and clinical response.", "contents": "Streptozocin-treated Verner-Morrison Syndrome: plasma vasoactive intestinal peptide and tumor responses. A patient with watery diarrhea, hypokalemia, hypochlorhydria, and a non-beta islet cell carcinoma of the pancreas (Verner-Morrison syndrome) was found to have an elevated vasoactive intestinal peptide (VIP) concentration in the plasma as well as in the tumor. Treatment with streptozocin resulted in a dramatic subjective and objective tumor response in this patient. Plasma VIP concentration fell into the normal range after four courses of treatment, diarrhea ceased after the third course of therapy, and measurable tumor mass markedly decreased during that same period of time. The patient remains in clinical remission with no evidence of tumor regrowth 18 months after the beginning of treatment. In this patient, plasma VIP measurements were an excellent marker of tumor activity and correlated well with objective disease measurements and clinical response."}
{"id": "PMID:187137", "title": "[Gluconeogenetic capacity of suckling piglets and young pigs].", "content": "No marked gluconeogenetic performance was recordable from nursed piglets aged, between one and five days, in response to ACTH nor glucocorticosteroid application. Store pigs, aged twelve weeks, however, exhibited glucose rises of 34 per cent one hour after injection or 55 per cent three hours from ACTH application. The point was made, in an attempt to elucidate the above findings, that in newborn piglets, few days after birth, the gluconeogenetic capacity is insufficient because of functional immaturity of the liver. The behaviours of several metabolites in the liver and muscles of store pigs were examined under differentiated model conditions to check up and verify that view.", "contents": "[Gluconeogenetic capacity of suckling piglets and young pigs]. No marked gluconeogenetic performance was recordable from nursed piglets aged, between one and five days, in response to ACTH nor glucocorticosteroid application. Store pigs, aged twelve weeks, however, exhibited glucose rises of 34 per cent one hour after injection or 55 per cent three hours from ACTH application. The point was made, in an attempt to elucidate the above findings, that in newborn piglets, few days after birth, the gluconeogenetic capacity is insufficient because of functional immaturity of the liver. The behaviours of several metabolites in the liver and muscles of store pigs were examined under differentiated model conditions to check up and verify that view."}
{"id": "PMID:187139", "title": "The influence of central chemical sympathectomy and reserpine on peripheral effects of noradrenaline and cyclic AMP dibutyrate injected into the cerebral ventricles.", "content": "Chemical sympathectomy of the central nervous system by injection of 6-hydroxy-dopamine (2 X 250 mug) or 6-hydroxydopa (90 mug) intensified some of the peripheral effects of noradrenaline and cyclic AMP dibutyrate injected into the cerebral ventricles. Reserpine (5 mg/kg) injected intraperitoneally weakened the peripheral reactions to noradrenaline injected intraventricularly. The results of the experiments indicate that peripheral reactions to intraventricularly injected noradrenaline depend on changes in the content of endogenous narodrenaline in the brain and on the mechanisms leading to these changes.", "contents": "The influence of central chemical sympathectomy and reserpine on peripheral effects of noradrenaline and cyclic AMP dibutyrate injected into the cerebral ventricles. Chemical sympathectomy of the central nervous system by injection of 6-hydroxy-dopamine (2 X 250 mug) or 6-hydroxydopa (90 mug) intensified some of the peripheral effects of noradrenaline and cyclic AMP dibutyrate injected into the cerebral ventricles. Reserpine (5 mg/kg) injected intraperitoneally weakened the peripheral reactions to noradrenaline injected intraventricularly. The results of the experiments indicate that peripheral reactions to intraventricularly injected noradrenaline depend on changes in the content of endogenous narodrenaline in the brain and on the mechanisms leading to these changes."}
{"id": "PMID:187140", "title": "AKR mouse leukemia cells in tissue culture. I. Establishment of leukemic cell line AKR 87 and its morphologic and biologic characteristics.", "content": "A line of AKR leukemic mouse cells cultured in vitro, designated AKR 87, was established and characterized. Two types of cells were distinguished in this line fibroblasts and lymphoblasts. The lymphoblast-like cells resembled the original tumor cells spontaneous leukemia of AKR mice. In the XC test, cells of this line reacted specifically with XC cells, forming syncytia characteristic of cells infected with mouse leukemia viruses. Ultrathin sections of cells of this line examined on the electron microscope showed presence of type C viral particles.", "contents": "AKR mouse leukemia cells in tissue culture. I. Establishment of leukemic cell line AKR 87 and its morphologic and biologic characteristics. A line of AKR leukemic mouse cells cultured in vitro, designated AKR 87, was established and characterized. Two types of cells were distinguished in this line fibroblasts and lymphoblasts. The lymphoblast-like cells resembled the original tumor cells spontaneous leukemia of AKR mice. In the XC test, cells of this line reacted specifically with XC cells, forming syncytia characteristic of cells infected with mouse leukemia viruses. Ultrathin sections of cells of this line examined on the electron microscope showed presence of type C viral particles."}
{"id": "PMID:187141", "title": "AKR mouse leukemic cells in tissue culture. II. Immunologic studies on the AKR 87 cell line.", "content": "The continuous AKR 87 cell line was derived from the thymus and spleen of AKR mice with spontaneous leukemia. Previous studies showed that the line has retained the original morphologic features of leukemic cells, reacts positively in the XC test, and produces virus particles of type C morphology. The present paper presents an immunologic characterization of cells of the AKR 87 line and of the virus produced by them, in comparison with the cells of spontaneous leukemia of AKR mice, TGV line productively infected with Gross virus, and normal mouse tissues. Results of the hemagglutination test, immunoprecipitation in agar gel, cytotoxic test and immunofluorescence indicate that the AKR 87 line produces virus antigen of the Gross type.", "contents": "AKR mouse leukemic cells in tissue culture. II. Immunologic studies on the AKR 87 cell line. The continuous AKR 87 cell line was derived from the thymus and spleen of AKR mice with spontaneous leukemia. Previous studies showed that the line has retained the original morphologic features of leukemic cells, reacts positively in the XC test, and produces virus particles of type C morphology. The present paper presents an immunologic characterization of cells of the AKR 87 line and of the virus produced by them, in comparison with the cells of spontaneous leukemia of AKR mice, TGV line productively infected with Gross virus, and normal mouse tissues. Results of the hemagglutination test, immunoprecipitation in agar gel, cytotoxic test and immunofluorescence indicate that the AKR 87 line produces virus antigen of the Gross type."}
{"id": "PMID:187142", "title": "Production of interferon in human diploid cell cultures.", "content": "Eleven human diploid cell lines were compared for their ability to produce interferon in response to Newcastle Disease Virus. Sensitivity of the cultures of MM, Sindbis VSV and VR viruses was also studied. Human cells derived from various tissue of a single embryo responded variably to interferon inducer. Using selected viruses interferon production was studied in two systems, in cultures of leukocytes and in human embryonic cells.", "contents": "Production of interferon in human diploid cell cultures. Eleven human diploid cell lines were compared for their ability to produce interferon in response to Newcastle Disease Virus. Sensitivity of the cultures of MM, Sindbis VSV and VR viruses was also studied. Human cells derived from various tissue of a single embryo responded variably to interferon inducer. Using selected viruses interferon production was studied in two systems, in cultures of leukocytes and in human embryonic cells."}
{"id": "PMID:187138", "title": "[Association of a bifocal nephroblastoma with Beckwith's syndrome].", "content": "A nephroblastoma occurred in the evolution of a case of Beckwith's syndrome. This rare association is not fortuitous. The bifocal character of the tumor is noted for the first time in the Beckwith's syndrome; however, it has already been observed in other conditions, which are known to promote the development of nephroblastomas. Wilm's tumor is only one of the tumors which may be associated with Beckwith's syndrome. These morbid associations and certain histological features bring together some material for the understanding of the nature of the histo-genetic relationship between different aspects of constitutional pathology and tumors.", "contents": "[Association of a bifocal nephroblastoma with Beckwith's syndrome]. A nephroblastoma occurred in the evolution of a case of Beckwith's syndrome. This rare association is not fortuitous. The bifocal character of the tumor is noted for the first time in the Beckwith's syndrome; however, it has already been observed in other conditions, which are known to promote the development of nephroblastomas. Wilm's tumor is only one of the tumors which may be associated with Beckwith's syndrome. These morbid associations and certain histological features bring together some material for the understanding of the nature of the histo-genetic relationship between different aspects of constitutional pathology and tumors."}
{"id": "PMID:187143", "title": "Chronic hypoxia and chemodectomas in bovines at high altitudes.", "content": "A severe degree of hyperplasia of the chief cells occurs in bovine carotid bodies at high altitudes, compared to sea level. As a result, the carotid body from an animal at high altitudes is significantly heavier and larger than the carotid body from an animal at sea level (P less than .001). In eight of 20 (40%) animals at high altitudes, the hyperplastic reaction had progressed to form chemodectomas. The findings suggest that neoplasia can result from chronic stimulation by a biologically essential environmental factor (atmospheric PO2) that acts pharmacologically on the target tissues (chief cells of the carotid body).", "contents": "Chronic hypoxia and chemodectomas in bovines at high altitudes. A severe degree of hyperplasia of the chief cells occurs in bovine carotid bodies at high altitudes, compared to sea level. As a result, the carotid body from an animal at high altitudes is significantly heavier and larger than the carotid body from an animal at sea level (P less than .001). In eight of 20 (40%) animals at high altitudes, the hyperplastic reaction had progressed to form chemodectomas. The findings suggest that neoplasia can result from chronic stimulation by a biologically essential environmental factor (atmospheric PO2) that acts pharmacologically on the target tissues (chief cells of the carotid body)."}
{"id": "PMID:187144", "title": "Morphogenesis of avian infectious bronchitis virus in primary chick kidney cells.", "content": "Primary chick kidney cells were infected with avian infectious bronchitis virus (IBV) and examined by electron microscopy. Virus particles entered the cells by viropexis and distinction could be made between engulfment by cell processes (phagocytosis) and entry by micropinocytosis in coated transport vesicles. Virus maturation occurred by budding into either the cisternae of the endoplasmic reticulum or cytoplasmic vacuoles, and evidence was obtained to suggest that the viral surface projections could be attached during the budding process. Late in infection large numbers of virus particles were present, mainly in cytoplasmic vacuoles, and the majority were released by cell lysis. Release by fusion of vacuoles with the plasma membrane was also observed, and individual virions could be transported from the endoplasmic reticulum to the surface within coated vesicles.", "contents": "Morphogenesis of avian infectious bronchitis virus in primary chick kidney cells. Primary chick kidney cells were infected with avian infectious bronchitis virus (IBV) and examined by electron microscopy. Virus particles entered the cells by viropexis and distinction could be made between engulfment by cell processes (phagocytosis) and entry by micropinocytosis in coated transport vesicles. Virus maturation occurred by budding into either the cisternae of the endoplasmic reticulum or cytoplasmic vacuoles, and evidence was obtained to suggest that the viral surface projections could be attached during the budding process. Late in infection large numbers of virus particles were present, mainly in cytoplasmic vacuoles, and the majority were released by cell lysis. Release by fusion of vacuoles with the plasma membrane was also observed, and individual virions could be transported from the endoplasmic reticulum to the surface within coated vesicles."}
{"id": "PMID:187145", "title": "Individual translational efficiencies of SV40 and cellular mRNAs.", "content": "The technique of selective inhibition of peptide chain initiation by growth medium hypertonicity was adapted for cell monolayer cultures and applied to a study of protein synthesis in SV40 infected BSC-1 cells. The translational efficiences for individual peptide chain initiation sites on SV40 mRNAs were determined and compared to those for cellular mRNA species under conditions of a reduced rate of peptide chain initiation. The SV40 mRNAs show different translational efficiences. The results indicate that the synthesis of the SV40 proteins VP1, 2 and 3 are initiated independently and with different rates on viral mRNA(s). It is proposed, therefore, that VP2 is not a precursor for VP3.", "contents": "Individual translational efficiencies of SV40 and cellular mRNAs. The technique of selective inhibition of peptide chain initiation by growth medium hypertonicity was adapted for cell monolayer cultures and applied to a study of protein synthesis in SV40 infected BSC-1 cells. The translational efficiences for individual peptide chain initiation sites on SV40 mRNAs were determined and compared to those for cellular mRNA species under conditions of a reduced rate of peptide chain initiation. The SV40 mRNAs show different translational efficiences. The results indicate that the synthesis of the SV40 proteins VP1, 2 and 3 are initiated independently and with different rates on viral mRNA(s). It is proposed, therefore, that VP2 is not a precursor for VP3."}
{"id": "PMID:187146", "title": "Antiviral activity of carbopol, a cross-linked polycarboxylate.", "content": "Carbopol, a polymer of acrylic acid cross-linked with allylsucrose, was found to impart resistance to virus infection in mice which received an intraperitoneal injection of the polycarboxylate 1 or 4 days before either intravenous vaccinia virus challenge or intranasal herpes simplex virus challenge. An interferon-like substance was detected in the blood stream 20-40 hours after the intraperitoneal injection of carbopol. The antiviral activity of this cross-linked polycarboxylate could be due to activation of peritoneal macrophages and/or interferon production.", "contents": "Antiviral activity of carbopol, a cross-linked polycarboxylate. Carbopol, a polymer of acrylic acid cross-linked with allylsucrose, was found to impart resistance to virus infection in mice which received an intraperitoneal injection of the polycarboxylate 1 or 4 days before either intravenous vaccinia virus challenge or intranasal herpes simplex virus challenge. An interferon-like substance was detected in the blood stream 20-40 hours after the intraperitoneal injection of carbopol. The antiviral activity of this cross-linked polycarboxylate could be due to activation of peritoneal macrophages and/or interferon production."}
{"id": "PMID:187148", "title": "In vivo antiviral activity of D-glucosamine.", "content": "Intraperitoneal treatments with D-glucosamine, an inhibitor of the glycosylation of the viral envelope, decreased the growth rate of tumors induced in quails or in chicks by Rous sarcoma virus and increased the survival of mice inoculated with human influenza virus.", "contents": "In vivo antiviral activity of D-glucosamine. Intraperitoneal treatments with D-glucosamine, an inhibitor of the glycosylation of the viral envelope, decreased the growth rate of tumors induced in quails or in chicks by Rous sarcoma virus and increased the survival of mice inoculated with human influenza virus."}
{"id": "PMID:187150", "title": "Comparison of the humoral and cellular immune response after immunization with live, UV inactivated herpes simplex virus and a subunit vaccine and efficacy of these immunizations.", "content": "Antibody and cell-mediated immune responses were measured in rabbits immunized with live, UV inactivated herpes simplex virus or with a subunit vaccine containing envelope proteins. All the types of immunization procedures induced the production of antibody as well as a specific cellular immunity. Furthermore, the subunit vaccine was as effective as the immunization with live or UV inactivated virus to prevent death upon challenge with live HSV. Live HSV induced a transient unresponsiveness of both B and T cells to in vitro stimulation with various mitogens.", "contents": "Comparison of the humoral and cellular immune response after immunization with live, UV inactivated herpes simplex virus and a subunit vaccine and efficacy of these immunizations. Antibody and cell-mediated immune responses were measured in rabbits immunized with live, UV inactivated herpes simplex virus or with a subunit vaccine containing envelope proteins. All the types of immunization procedures induced the production of antibody as well as a specific cellular immunity. Furthermore, the subunit vaccine was as effective as the immunization with live or UV inactivated virus to prevent death upon challenge with live HSV. Live HSV induced a transient unresponsiveness of both B and T cells to in vitro stimulation with various mitogens."}
{"id": "PMID:187151", "title": "Inhibitors of foot-and-mouth disease virus. Temperature-dependence of the effect of guanidine on virus growth.", "content": "In suspended secondary calf kidney cells infected with foot-and-mouth disease virus (FMDV) the temperature range for optimal virus growth is shifted down by 3 to 5 degrees C in the presence of 1--2 mM guanidine. For some virus strains this shift is so effective that at infraoptimal temperatures virus yield in guanidine-treated cells exceeds that of the corresponding control by more than one log10. On the contrary, at supraoptimal temperatures inhibition of virus growth by the drug is strongly enhanced. At a concentration of 1 to 2 mM guanidine virus yield reduction or enhancement is based on a decrease in increase, respectively, of the number of virus producing cells (infective centers; I.C.), while virus yield per I.C. is less affected. Besides this \"thermomimetic\" effect virus production is inhibited by guanidine depending on the concentration of this substance. A mutant of FMDV strain O1L, resistant to 4.2 guanidine, did not differ from the original virus in its antigenic behaviour in the passive immunohemolysis test.", "contents": "Inhibitors of foot-and-mouth disease virus. Temperature-dependence of the effect of guanidine on virus growth. In suspended secondary calf kidney cells infected with foot-and-mouth disease virus (FMDV) the temperature range for optimal virus growth is shifted down by 3 to 5 degrees C in the presence of 1--2 mM guanidine. For some virus strains this shift is so effective that at infraoptimal temperatures virus yield in guanidine-treated cells exceeds that of the corresponding control by more than one log10. On the contrary, at supraoptimal temperatures inhibition of virus growth by the drug is strongly enhanced. At a concentration of 1 to 2 mM guanidine virus yield reduction or enhancement is based on a decrease in increase, respectively, of the number of virus producing cells (infective centers; I.C.), while virus yield per I.C. is less affected. Besides this \"thermomimetic\" effect virus production is inhibited by guanidine depending on the concentration of this substance. A mutant of FMDV strain O1L, resistant to 4.2 guanidine, did not differ from the original virus in its antigenic behaviour in the passive immunohemolysis test."}
{"id": "PMID:187152", "title": "Electron microscope observations on the entry of avian infectious bronchitis virus into susceptible cells.", "content": "Infectious bronchitis virus was observed to enter cells of chicken chorioallantoic membrane by viropexis. There was no support for the suggestion that entry took place by fusion of viral and plasma membranes. The results of electron microscopy showed that virus attachment occurred both at 4 degrees and at 37 degrees C. Viropexis was not observed until the preparations were warmed. Similar results were obtained using chicken kidney cells. Quantitative data obtained from a plaque counting system employing chicken kidney cells indicated that attachment was the same at both temperatures and that some virus particles were taken up at 4 degrees C. Virus uptake was triggered by attachment of the virus to the cell membrane and the subsequent process of virus entry visualised by E. M. appeared to proceed without the involvement of lysosomal enzymes. No intracellular virus was located by electron microscopy in warmed preparations when virus was treated with specific antiserum, either before or after adsorption to the cells.", "contents": "Electron microscope observations on the entry of avian infectious bronchitis virus into susceptible cells. Infectious bronchitis virus was observed to enter cells of chicken chorioallantoic membrane by viropexis. There was no support for the suggestion that entry took place by fusion of viral and plasma membranes. The results of electron microscopy showed that virus attachment occurred both at 4 degrees and at 37 degrees C. Viropexis was not observed until the preparations were warmed. Similar results were obtained using chicken kidney cells. Quantitative data obtained from a plaque counting system employing chicken kidney cells indicated that attachment was the same at both temperatures and that some virus particles were taken up at 4 degrees C. Virus uptake was triggered by attachment of the virus to the cell membrane and the subsequent process of virus entry visualised by E. M. appeared to proceed without the involvement of lysosomal enzymes. No intracellular virus was located by electron microscopy in warmed preparations when virus was treated with specific antiserum, either before or after adsorption to the cells."}
{"id": "PMID:187153", "title": "Comparative studies on the structural proteins of T3 and T7 phages.", "content": "A comparison of the coat protein patterns of the wild types of the related phages T3 and T7 on SDS polyacrylamide gel electrophoresis was carried out. After infection of the nonpermissive host with T7 amber mutants in genes 7, 11, 12, 13 or 17 and T3 amber mutants in genes 11, 12, 13 and 17 respectively, noninfectious, DNA containing particles were produced. The protein pattern, as well as electron microscopy of defective particles of T3 and T7 led to the conclusion that the proteins specified by genes 11, 12, 13 and 17 are tail proteins whereas the proteins coded by genes 7, 8, 10, 14, 15 and 16 enter the head structure. The \"serum blocking protein\" (gene 17 product) seems to play a different role in the assembly of T3 and T7 tails, since T3 particles defective in gene 17 did not show any tail structure connected with the head whereas T7 particles defective in gene 17 had a tail which looked different from that of the wildtype. Treatment of wildtype particles with ammonium nitrate or sodium pyrophosphate led to morphologically abberrant forms which had partially or completely lost the hexagonal head structure. After treatment with ammonium nitrate ball-like structures were obtained, both for T3 and T7. However, in the case of T3 these abberrant forms contained the proteins specified by genes 7, 8 and 10 whereas those derived from T7 contained only the proteins specified by genes 8 and 10. Sodium pyrophosphate treatment of T3 and T7 wildtype particles led to a release of the phage tails. The isolated tails were examined by electron microscopy thus revealing for the first time a detailed substructure of the T3 and T7 phage tails. In order to find out more about the tail proteins, absorption experiments with isolated bacterial cell walls were carried out.", "contents": "Comparative studies on the structural proteins of T3 and T7 phages. A comparison of the coat protein patterns of the wild types of the related phages T3 and T7 on SDS polyacrylamide gel electrophoresis was carried out. After infection of the nonpermissive host with T7 amber mutants in genes 7, 11, 12, 13 or 17 and T3 amber mutants in genes 11, 12, 13 and 17 respectively, noninfectious, DNA containing particles were produced. The protein pattern, as well as electron microscopy of defective particles of T3 and T7 led to the conclusion that the proteins specified by genes 11, 12, 13 and 17 are tail proteins whereas the proteins coded by genes 7, 8, 10, 14, 15 and 16 enter the head structure. The \"serum blocking protein\" (gene 17 product) seems to play a different role in the assembly of T3 and T7 tails, since T3 particles defective in gene 17 did not show any tail structure connected with the head whereas T7 particles defective in gene 17 had a tail which looked different from that of the wildtype. Treatment of wildtype particles with ammonium nitrate or sodium pyrophosphate led to morphologically abberrant forms which had partially or completely lost the hexagonal head structure. After treatment with ammonium nitrate ball-like structures were obtained, both for T3 and T7. However, in the case of T3 these abberrant forms contained the proteins specified by genes 7, 8 and 10 whereas those derived from T7 contained only the proteins specified by genes 8 and 10. Sodium pyrophosphate treatment of T3 and T7 wildtype particles led to a release of the phage tails. The isolated tails were examined by electron microscopy thus revealing for the first time a detailed substructure of the T3 and T7 phage tails. In order to find out more about the tail proteins, absorption experiments with isolated bacterial cell walls were carried out."}
{"id": "PMID:187154", "title": "Biological and electron microscopic studies on the phenotypic mixing of the thermolabile mutant of vesicular stomatitis virus, tl-17, with avian RNA tumor viruses.", "content": "A thermolabile as well as thermosensitive mutant of vesicular stomatitis virus, VSV-tl-17, could be thermostabilized by phenotypic mixing with avian RNA tumor viruses (ATV). Biological, immunological and morphological studies revealed that this effect is due to a replacement of the thermolabile projections of the VSV by the avian tumor viral projections. The arrangement of projections of VSV and ATV on phenotypically mixed viria was studied by electron microscopy. A-type particles were detected in chick embryo cells which were doubly infected by ATV and VSV. Their intracytoplasmic appearance seemed to be the result of a disturbed maturation of ATV due to the relative deficiency of envelope proteins which were depleted by VSV maturation in the course of phenotypic mixing.", "contents": "Biological and electron microscopic studies on the phenotypic mixing of the thermolabile mutant of vesicular stomatitis virus, tl-17, with avian RNA tumor viruses. A thermolabile as well as thermosensitive mutant of vesicular stomatitis virus, VSV-tl-17, could be thermostabilized by phenotypic mixing with avian RNA tumor viruses (ATV). Biological, immunological and morphological studies revealed that this effect is due to a replacement of the thermolabile projections of the VSV by the avian tumor viral projections. The arrangement of projections of VSV and ATV on phenotypically mixed viria was studied by electron microscopy. A-type particles were detected in chick embryo cells which were doubly infected by ATV and VSV. Their intracytoplasmic appearance seemed to be the result of a disturbed maturation of ATV due to the relative deficiency of envelope proteins which were depleted by VSV maturation in the course of phenotypic mixing."}
{"id": "PMID:187155", "title": "The pathogenesis of vesicular stomatitis virus, serotype Indiana, in Aedes aegypti mosquitoes, after imbibition of a viremic blood meal.", "content": "This study showed that Vesicular Stomatitis Virus (Indiana) in most instances was not capable of replicating in Aedes aegypti when imbibed by the mosquitoes on a viremic host. Rapid inactivation of the virus was observed in some cases within 24 hours after imbibition. Attempts to demonstrate virus inactivation by midgut contents in vitro were not successful.", "contents": "The pathogenesis of vesicular stomatitis virus, serotype Indiana, in Aedes aegypti mosquitoes, after imbibition of a viremic blood meal. This study showed that Vesicular Stomatitis Virus (Indiana) in most instances was not capable of replicating in Aedes aegypti when imbibed by the mosquitoes on a viremic host. Rapid inactivation of the virus was observed in some cases within 24 hours after imbibition. Attempts to demonstrate virus inactivation by midgut contents in vitro were not successful."}
{"id": "PMID:187156", "title": "Mucolipidosis IV. Clinical, ultrastructural, histochemical, and chemical studies of a case, including a brain biopsy.", "content": "A 7-year-old Ashkenazi Jewish boy with normal early development started to regress at 8 months of age and made no further developmental progress. Corneal clouding was noted at age 10 months. Corneal and conjunctival biopsy at 14 months, cerebral biopsy at 24 months, and fibroblast cultures at 32 months showed lysosomal inclusions, suggesting the storage of lipid-like and mucopolysaccharide-like material. In the brain, dense fluorescent inclusions resembled those in ceroid-lipofuscinosis. Total ganglioside content of white matter was raised, but the pattern was normal. The level of nonlipid hexosamine in the brain was normal. The cornea and conjunctiva contained electronlucent vacuoles resembling those in the mucopolysaccharidoses. Cornea, brain, and lymphocytes contained concentric membranous lamellar structures reminiscent of those in the gangliosidoses. The clinical picture and ultrastructural findings support the impression that this case belongs to a new variant of the mucolipidoses, mucolipidosis IV.", "contents": "Mucolipidosis IV. Clinical, ultrastructural, histochemical, and chemical studies of a case, including a brain biopsy. A 7-year-old Ashkenazi Jewish boy with normal early development started to regress at 8 months of age and made no further developmental progress. Corneal clouding was noted at age 10 months. Corneal and conjunctival biopsy at 14 months, cerebral biopsy at 24 months, and fibroblast cultures at 32 months showed lysosomal inclusions, suggesting the storage of lipid-like and mucopolysaccharide-like material. In the brain, dense fluorescent inclusions resembled those in ceroid-lipofuscinosis. Total ganglioside content of white matter was raised, but the pattern was normal. The level of nonlipid hexosamine in the brain was normal. The cornea and conjunctiva contained electronlucent vacuoles resembling those in the mucopolysaccharidoses. Cornea, brain, and lymphocytes contained concentric membranous lamellar structures reminiscent of those in the gangliosidoses. The clinical picture and ultrastructural findings support the impression that this case belongs to a new variant of the mucolipidoses, mucolipidosis IV."}
{"id": "PMID:187157", "title": "Axonal degeneration in beriberi neuropathy.", "content": "Ultrastructural and teased-fiber studies were carried out on the sural nerves of nine patients with beriberi neuropathy Axonal degeneration was the most prominent feature, and large myelinated fibers were more affected than unmyelinated ones. An unusual change with accumulation of flattened sacs or tubuli was recognized in the axoplasm of myelinated fibers of untreated patients. Active regeneration was extensive in patients receiving vitamin B. Segmental demyelination, remyelination, and early onion bulbs were scarece in patients with a long and relapsing course before treatment.", "contents": "Axonal degeneration in beriberi neuropathy. Ultrastructural and teased-fiber studies were carried out on the sural nerves of nine patients with beriberi neuropathy Axonal degeneration was the most prominent feature, and large myelinated fibers were more affected than unmyelinated ones. An unusual change with accumulation of flattened sacs or tubuli was recognized in the axoplasm of myelinated fibers of untreated patients. Active regeneration was extensive in patients receiving vitamin B. Segmental demyelination, remyelination, and early onion bulbs were scarece in patients with a long and relapsing course before treatment."}
{"id": "PMID:187158", "title": "Peripheral nerve involvement in Hunter syndrome (mucopolysaccharidosis II).", "content": "A 20-year-old man with confirmed Hunter syndrome had entrapments of median and ulnar nerves. Sural nerve biopsy specimen revealed clear, lamellated, and granular inclusions in Schwann cells, fibroblasts, and perineurial cells. The clear inclusions are believed to represent storage of mucopolysaccharide, and the zebra bodies, ganglioside. Focal alterations in myelin were found, associated with moderately dense granular inclusions. Following carpal tunnel release operations, the patient experienced dramatic releif of symptoms.", "contents": "Peripheral nerve involvement in Hunter syndrome (mucopolysaccharidosis II). A 20-year-old man with confirmed Hunter syndrome had entrapments of median and ulnar nerves. Sural nerve biopsy specimen revealed clear, lamellated, and granular inclusions in Schwann cells, fibroblasts, and perineurial cells. The clear inclusions are believed to represent storage of mucopolysaccharide, and the zebra bodies, ganglioside. Focal alterations in myelin were found, associated with moderately dense granular inclusions. Following carpal tunnel release operations, the patient experienced dramatic releif of symptoms."}
{"id": "PMID:187159", "title": "Granular cell myoblastoma of the orbit. Report of a case.", "content": "A light and electron microscopical study of a case of granular cell myoblastoma of the orbit is described. Its possible histogenesis is discussed and, from the study of this case and of the literature, it is believed that the most likely histogenesis is from a primitive mesenchymal cell resembling a fibroblast.", "contents": "Granular cell myoblastoma of the orbit. Report of a case. A light and electron microscopical study of a case of granular cell myoblastoma of the orbit is described. Its possible histogenesis is discussed and, from the study of this case and of the literature, it is believed that the most likely histogenesis is from a primitive mesenchymal cell resembling a fibroblast."}
{"id": "PMID:187160", "title": "The placement of viruses in the aetiology of cancer.", "content": "The role of viruses as causative agents of cancer in man has been examined for more than 50 years. These studies have recently been intensified by employing newly developed, more sensitive techniques in virology and immunology. In spite of proof that viruses cause cancer in animals and that about one-quarter of the known 600 viruses possess oncogenic potential, definite proof of their aetiology in human cancer remains elusive even though cancer research is a highly respectable and costly pursuit. Nevertheless, the probabilities are high that human cancer viruses have been and will be identified and that their induced diseases can be prevented or controlled. It is accepted that some benign tumours of man (such as warts) are induced by a virus infection. This article examines the current situation and highlights the difficulties, hopes and usefulness of research in this field.", "contents": "The placement of viruses in the aetiology of cancer. The role of viruses as causative agents of cancer in man has been examined for more than 50 years. These studies have recently been intensified by employing newly developed, more sensitive techniques in virology and immunology. In spite of proof that viruses cause cancer in animals and that about one-quarter of the known 600 viruses possess oncogenic potential, definite proof of their aetiology in human cancer remains elusive even though cancer research is a highly respectable and costly pursuit. Nevertheless, the probabilities are high that human cancer viruses have been and will be identified and that their induced diseases can be prevented or controlled. It is accepted that some benign tumours of man (such as warts) are induced by a virus infection. This article examines the current situation and highlights the difficulties, hopes and usefulness of research in this field."}
{"id": "PMID:187161", "title": "Why sleep?", "content": "Alert clinicians realize that much more data are fragmentedly available than has coherently been assimilated for practical application to the understanding of sleep--its vital function, its vicissitudes and its values. Now may be the time to add to sleep research, a dimension of field trips away from the labs. Cross cultural data might also be correlated, bringing social anthropologists and sleep physiologists together for didactic exchange.", "contents": "Why sleep? Alert clinicians realize that much more data are fragmentedly available than has coherently been assimilated for practical application to the understanding of sleep--its vital function, its vicissitudes and its values. Now may be the time to add to sleep research, a dimension of field trips away from the labs. Cross cultural data might also be correlated, bringing social anthropologists and sleep physiologists together for didactic exchange."}
{"id": "PMID:187163", "title": "[The quantitative cytoarchitecture of Morris hepatoma 66 (author's transl)].", "content": "To obtain a statistic comparable picturg oncogenesis, tissue of a middle-fast growing Morris-hepatoma 66 was transplanted into the femoral musculature. 35 days later the animals were killed by decapitation and hepatoma tissue was taken. The morphometric analysis based on the technique described by Weibel (1969). In the Morris-hepatoma 66 hepatocyte and nucleus show a much smaller single volume in comparison to normal liver cell. Smaller is also the number of nucleoli per nucleus. The decreased numerical density of mitochondria in liver tissue and their smaller content of mitochondrial grana suggest a reduction of the oxidative metabolism. The enlargement of membrane surface of the rough endoplasmatic reticulum in liver tissue is accompanied by a cisternal collapse. The smooth endoplastmatic reticulum is rudimentary in the hepatoma cells. The number of peroxisomes is equal in hepatoma and normal liver. Only half as large is, however, their volume density in liver tissue and so also their single volume.", "contents": "[The quantitative cytoarchitecture of Morris hepatoma 66 (author's transl)]. To obtain a statistic comparable picturg oncogenesis, tissue of a middle-fast growing Morris-hepatoma 66 was transplanted into the femoral musculature. 35 days later the animals were killed by decapitation and hepatoma tissue was taken. The morphometric analysis based on the technique described by Weibel (1969). In the Morris-hepatoma 66 hepatocyte and nucleus show a much smaller single volume in comparison to normal liver cell. Smaller is also the number of nucleoli per nucleus. The decreased numerical density of mitochondria in liver tissue and their smaller content of mitochondrial grana suggest a reduction of the oxidative metabolism. The enlargement of membrane surface of the rough endoplasmatic reticulum in liver tissue is accompanied by a cisternal collapse. The smooth endoplastmatic reticulum is rudimentary in the hepatoma cells. The number of peroxisomes is equal in hepatoma and normal liver. Only half as large is, however, their volume density in liver tissue and so also their single volume."}
{"id": "PMID:187164", "title": "[Congenital mesoblastic nephroma - a semimalignant fibroleiomyomatous kidney tumor of the newborn (author's transl)].", "content": "The congenital mesoblastic nephroma is a distinct tumor entity, which should be clearly distinguished from Wilmus-tumor. The pure mesenchymal tumor is usually present at birth and palpated as a mass in the kidney. Macroscopically the tumor reveals a striking resemblance with an uterine fibroid. Histologically the tumor tissue ist characterized by 1. interlacing bundels of spindle cells with uniform cell nuclei and regular mitotic figures, 2. collagen fibres between the tumor cells, 3. an angiomatous marginal zone, no tumor capsule, 4. hematopoetic foci and dysplastic glomeruli and tubuli in areas where normal kidney parenchyma mixes with tumor tissue, 5. small myxomatous areas within in the tumor, 6. no invasion of blood vessels or pelvis. Prognosis of the congenital mesoblastic nephroma is much better than in Wilms-tumor. Metastases have not been described so far. If, however, the tumor tissue is incompletly removed during operation, the neoplasm may recur and prove fatal. Ultrastructural and DNA cytophotometric studies suggests a low grade malignancy rather than a truely benign behaviour of this tumor.", "contents": "[Congenital mesoblastic nephroma - a semimalignant fibroleiomyomatous kidney tumor of the newborn (author's transl)]. The congenital mesoblastic nephroma is a distinct tumor entity, which should be clearly distinguished from Wilmus-tumor. The pure mesenchymal tumor is usually present at birth and palpated as a mass in the kidney. Macroscopically the tumor reveals a striking resemblance with an uterine fibroid. Histologically the tumor tissue ist characterized by 1. interlacing bundels of spindle cells with uniform cell nuclei and regular mitotic figures, 2. collagen fibres between the tumor cells, 3. an angiomatous marginal zone, no tumor capsule, 4. hematopoetic foci and dysplastic glomeruli and tubuli in areas where normal kidney parenchyma mixes with tumor tissue, 5. small myxomatous areas within in the tumor, 6. no invasion of blood vessels or pelvis. Prognosis of the congenital mesoblastic nephroma is much better than in Wilms-tumor. Metastases have not been described so far. If, however, the tumor tissue is incompletly removed during operation, the neoplasm may recur and prove fatal. Ultrastructural and DNA cytophotometric studies suggests a low grade malignancy rather than a truely benign behaviour of this tumor."}
{"id": "PMID:187165", "title": "[Diagnosis and differential diagnosis of rinderpest].", "content": "Starting from the clinical symptoms and the pathological-anatomical changes hints are given on the diagnosis of the rinderpest and how to distinguish it from other diseases. The paper discusses the differential diagnosis of the rinderpest with respect to mucosal disease, malignent catarrhal fever, Nairobi sheep disease, salmonellosis, pasteurellosis, and coccidiosis.", "contents": "[Diagnosis and differential diagnosis of rinderpest]. Starting from the clinical symptoms and the pathological-anatomical changes hints are given on the diagnosis of the rinderpest and how to distinguish it from other diseases. The paper discusses the differential diagnosis of the rinderpest with respect to mucosal disease, malignent catarrhal fever, Nairobi sheep disease, salmonellosis, pasteurellosis, and coccidiosis."}
{"id": "PMID:187168", "title": "Particulate' hexokinase activity in rat intestine. The comparative contributions of mitochondria and brush-border membranes.", "content": "The activity of hexokinase was examined in brush-border membranes purified from rat intestine. Compared with homogenates, purified membranes exhibited a 20-fold increase in sucrase specific activity and a 15-fold decrease in hexokinase specific activity, which argues against the structural localization of hexokinase within the brush-border membrane.", "contents": "Particulate' hexokinase activity in rat intestine. The comparative contributions of mitochondria and brush-border membranes. The activity of hexokinase was examined in brush-border membranes purified from rat intestine. Compared with homogenates, purified membranes exhibited a 20-fold increase in sucrase specific activity and a 15-fold decrease in hexokinase specific activity, which argues against the structural localization of hexokinase within the brush-border membrane."}
{"id": "PMID:187169", "title": "Carboxymethylation of methionine residues in bovine pituitary luteinizing hormone and its subunits. Effects on the binding activity with receptor sites and interactions between subunits.", "content": "The reaction of iodoacetic acid with bovine lutropin (luteinizing hormone) at pH 3.0 was specific for methionine residues; it was slow and reached its equilibrium after 12 h at 37 degrees C. The number of modified methionine residues increased proportionately with the amount of the alkylating reagent in the reaction mixture. In the presence of a 20-fold molar excess of iodoacetic acid with respect to methionine, essentially all methionine residues in both subunits of bovine lutropin were carboxymethylated. Studies of various recombinations of modified and native alpha and beta subunits showed that methionine residues in bovine lutropin were not essential for interactions between subunits. Various recombinants were characterized by polyacrylamide-gel electrophoresis and gel filtration of Sephadex G-100. Immunological cross-reactivity by radioimmunoassay of the recombinants of modified alpha and beta subunits was relatively similar to that of the native subunits. However, the biological activity measured by receptor-site binding of the recombinants of alpha and beta chains with a total of three alkylated methionine residues was less than 5% of the activity of native lutropin. It is noteworthy that recombinants of a modified subunit and a native counterpart subunit regenerated 20-30 % of biological activity. These findings suggested that at least 1-2 methionine residues in each subunit are involved in the hormone-receptor interaction for bovine lutropin.", "contents": "Carboxymethylation of methionine residues in bovine pituitary luteinizing hormone and its subunits. Effects on the binding activity with receptor sites and interactions between subunits. The reaction of iodoacetic acid with bovine lutropin (luteinizing hormone) at pH 3.0 was specific for methionine residues; it was slow and reached its equilibrium after 12 h at 37 degrees C. The number of modified methionine residues increased proportionately with the amount of the alkylating reagent in the reaction mixture. In the presence of a 20-fold molar excess of iodoacetic acid with respect to methionine, essentially all methionine residues in both subunits of bovine lutropin were carboxymethylated. Studies of various recombinations of modified and native alpha and beta subunits showed that methionine residues in bovine lutropin were not essential for interactions between subunits. Various recombinants were characterized by polyacrylamide-gel electrophoresis and gel filtration of Sephadex G-100. Immunological cross-reactivity by radioimmunoassay of the recombinants of modified alpha and beta subunits was relatively similar to that of the native subunits. However, the biological activity measured by receptor-site binding of the recombinants of alpha and beta chains with a total of three alkylated methionine residues was less than 5% of the activity of native lutropin. It is noteworthy that recombinants of a modified subunit and a native counterpart subunit regenerated 20-30 % of biological activity. These findings suggested that at least 1-2 methionine residues in each subunit are involved in the hormone-receptor interaction for bovine lutropin."}
{"id": "PMID:187170", "title": "Amino acid sequence of cytochrome c from Tetrahymena pyriformis Phenoset A.", "content": "The cytochrome c of Tetrahymena pyriformis GL (Phenoset A) had an isoelectric point of 6.5 and by sequence the following composition: Asp(7) Asn(2) Thr(4) Ser(8) Glu(6) Gln(2) Pro(7) Gly(13) Ala(13) Val(7) Met(2) Ile(5) Leu(6) Tyr(2) Phe(5) Lys(11) His(3) Trp(1) Arg(3) Cys(2) (total 109 residues). The peptides derived from the protein afforded complete overlap, so a complete sequence could be determined without reference of homologous proteins. Alignment with other mitochondrial cytochromes c required two internal deletions totalling three residues and an N-terminal region two residues longer than, and a C-terminal region one residue shorter than, the previously known limits. The sequence was the most divergent of the known mitochondrial cytochromes c, suggesting a distant relationship of ciliates to other eukaryotes. Details of the sequence data have been deposited as Supplementary Publication no. SUP 50068 (37 pages) at The British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7 BQ, U.K., from whom copies can be obtained on the terms given in Biochem. J. (1976) 153,5.", "contents": "Amino acid sequence of cytochrome c from Tetrahymena pyriformis Phenoset A. The cytochrome c of Tetrahymena pyriformis GL (Phenoset A) had an isoelectric point of 6.5 and by sequence the following composition: Asp(7) Asn(2) Thr(4) Ser(8) Glu(6) Gln(2) Pro(7) Gly(13) Ala(13) Val(7) Met(2) Ile(5) Leu(6) Tyr(2) Phe(5) Lys(11) His(3) Trp(1) Arg(3) Cys(2) (total 109 residues). The peptides derived from the protein afforded complete overlap, so a complete sequence could be determined without reference of homologous proteins. Alignment with other mitochondrial cytochromes c required two internal deletions totalling three residues and an N-terminal region two residues longer than, and a C-terminal region one residue shorter than, the previously known limits. The sequence was the most divergent of the known mitochondrial cytochromes c, suggesting a distant relationship of ciliates to other eukaryotes. Details of the sequence data have been deposited as Supplementary Publication no. SUP 50068 (37 pages) at The British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7 BQ, U.K., from whom copies can be obtained on the terms given in Biochem. J. (1976) 153,5."}
{"id": "PMID:187171", "title": "Identification of cysteine as the reactive group in pyruvate kinase alkylated by 5-chloro-4-oxopentanoic acid.", "content": "4-Hydroxypentanoic acid alanine thioether was synthesized and characterized by n.m.r. spectroscopy. This derivative corresponded to the modified amino acid obtained by allowing 5-chloro-4-oxo[3,5-3H]pentanoic acid to react with rabbit muscle pyruvate kinase. Performic acid oxidation of 4-oxo[3,5-3H]pentanoic acid alanine thioether in pyruvate kinase gave [3H]succinate (67%) and [3H]carboxymethylcysteine (33%) as expected. Evidence is presented to show that NaBH4 reduction followed by periodate oxidation and analysis of radioactive formaldehyde production may provide a convenient method for distinguishing between thiol and amino alkylation by halogenomethyl ketone compounds. Peptide 'mapping' confirms that the modification by 5-chloro-4-oxopentanoic acid occurs primarily at one region of pyruvate kinase.", "contents": "Identification of cysteine as the reactive group in pyruvate kinase alkylated by 5-chloro-4-oxopentanoic acid. 4-Hydroxypentanoic acid alanine thioether was synthesized and characterized by n.m.r. spectroscopy. This derivative corresponded to the modified amino acid obtained by allowing 5-chloro-4-oxo[3,5-3H]pentanoic acid to react with rabbit muscle pyruvate kinase. Performic acid oxidation of 4-oxo[3,5-3H]pentanoic acid alanine thioether in pyruvate kinase gave [3H]succinate (67%) and [3H]carboxymethylcysteine (33%) as expected. Evidence is presented to show that NaBH4 reduction followed by periodate oxidation and analysis of radioactive formaldehyde production may provide a convenient method for distinguishing between thiol and amino alkylation by halogenomethyl ketone compounds. Peptide 'mapping' confirms that the modification by 5-chloro-4-oxopentanoic acid occurs primarily at one region of pyruvate kinase."}
{"id": "PMID:187172", "title": "The action of snake venom, phospholipase A and trypsin on purified myelin in vitro.", "content": "1. Purified myelin was incubated with snake venom or phospholipase A in the presence of or absence of trypsin at 37 degrees C, pH7.4, for different times. 2. Analysis of the myelin pellet obtained after centrifugation of the myelin sample incubated with snake venom or phospholipase A alone showed conversion of phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine into their corresponding lyso compounds. No significant loss of myelin protein was observed in these samples. 3. A marked digestion of basic proteins and proteolipid protein was observed from the myelin pellet when trypsin was present in the incubation mixture. 4. The digestion of basic protein and particularly of proteolipid from myelin suggest that phospholipases may make protein more exposed to proteolytic enzyme for its digestion. 5. The relevance of the co-operative effect of phospholipases and proteinases as a model system of the mechanism of myelin breakdown in degenerative brain diseases is discussed.", "contents": "The action of snake venom, phospholipase A and trypsin on purified myelin in vitro. 1. Purified myelin was incubated with snake venom or phospholipase A in the presence of or absence of trypsin at 37 degrees C, pH7.4, for different times. 2. Analysis of the myelin pellet obtained after centrifugation of the myelin sample incubated with snake venom or phospholipase A alone showed conversion of phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine into their corresponding lyso compounds. No significant loss of myelin protein was observed in these samples. 3. A marked digestion of basic proteins and proteolipid protein was observed from the myelin pellet when trypsin was present in the incubation mixture. 4. The digestion of basic protein and particularly of proteolipid from myelin suggest that phospholipases may make protein more exposed to proteolytic enzyme for its digestion. 5. The relevance of the co-operative effect of phospholipases and proteinases as a model system of the mechanism of myelin breakdown in degenerative brain diseases is discussed."}
{"id": "PMID:187173", "title": "Circular-dichroism and electron-microscopy studies of human subcomponent C1q before and after limited proteolysis by pepsin.", "content": "1. A fragment of human subcomponent C1q was prepared by limited proteolysis with pepsin at 37 degrees C for 20 h, and at pH4.4, followed by gel filtration on Sephadex G-200. This fragment was shown to contain all the collagen-like features known to be present in the intact molecule [Reid (1976) Biochem. J. 155, 5-17]. 2. Circular-dichroism studies showed the presence of positive bands at 230 and 223 nm in the intact subcomponent C1q and pepsin fragment respectively, compared with a positive band at 220 nm obtained for lathyritic rat skin collagen. These bands were abolished by collagenase treatment, which suggested that there may some collagen-like triple-helical structure in subcomponent C1q and that this structure resides in the pepsin-resistant portion of the molecule. However, the 230 and 223 nm bands had a substantially lower magnitude than that obtained for the unaggregated single fibres of totally triple-helical collagen. 3. Thermal-transition temperatures obtained for subcomponent C1q, the pepsin fragment and the reduced and alkylated pepsin fragment were 48 degrees, 48 degrees and 39 degrees C respectively, compared with a value of 38 degrees C obtained for lathyritic rat skin collagen. 4. Only the unreduced pepsin fragment regained significant amounts (up to 60%) of collagen-like structure, after heat denaturation and cooling, as estimated by circular-dichroism measurements. 5. Electron-microscopy studies of subcomponent C1q and the collagen-like pepsin-resistant fragment of subcomponent C1q showed that the six peripheral globular regions of the molecule were fragmented by pepsin leaving the six collagen-like connecting strands and fibril-like central portion intact.", "contents": "Circular-dichroism and electron-microscopy studies of human subcomponent C1q before and after limited proteolysis by pepsin. 1. A fragment of human subcomponent C1q was prepared by limited proteolysis with pepsin at 37 degrees C for 20 h, and at pH4.4, followed by gel filtration on Sephadex G-200. This fragment was shown to contain all the collagen-like features known to be present in the intact molecule [Reid (1976) Biochem. J. 155, 5-17]. 2. Circular-dichroism studies showed the presence of positive bands at 230 and 223 nm in the intact subcomponent C1q and pepsin fragment respectively, compared with a positive band at 220 nm obtained for lathyritic rat skin collagen. These bands were abolished by collagenase treatment, which suggested that there may some collagen-like triple-helical structure in subcomponent C1q and that this structure resides in the pepsin-resistant portion of the molecule. However, the 230 and 223 nm bands had a substantially lower magnitude than that obtained for the unaggregated single fibres of totally triple-helical collagen. 3. Thermal-transition temperatures obtained for subcomponent C1q, the pepsin fragment and the reduced and alkylated pepsin fragment were 48 degrees, 48 degrees and 39 degrees C respectively, compared with a value of 38 degrees C obtained for lathyritic rat skin collagen. 4. Only the unreduced pepsin fragment regained significant amounts (up to 60%) of collagen-like structure, after heat denaturation and cooling, as estimated by circular-dichroism measurements. 5. Electron-microscopy studies of subcomponent C1q and the collagen-like pepsin-resistant fragment of subcomponent C1q showed that the six peripheral globular regions of the molecule were fragmented by pepsin leaving the six collagen-like connecting strands and fibril-like central portion intact."}
{"id": "PMID:187174", "title": "Location of nucleotide pyrophosphatase and alkaline phosphodiesterase activities on the lymphocyte surface membrane.", "content": "1. Isolated mouse spleen lymphocytes hydrolysed UDP-galactose added to the medium. Nucleotide pyrophosphatase activity that accounted for this hydrolysis was enriched to a similar extent as alkaline phosphodiesterase and 5'-nucleotidase in a lymphocyte plasma-membrane fraction. 2. The cell surfaces of mouse spleen and thymus lymphocytes were iodinated with 125I by using the lactoperoxidase-catalysis method. Detergent extracts of the cells were mixed with a purified anti-(mouse liver plasma-membrane nucleotide pyrophosphatase) antiserum and the immunoprecipitates analysed by polyacrylamide-gel electrophoresis. Only one major radioactive component, similar in size (apparent mol.wt 110000-130000) to the liver enzyme, was observed. 3. Electrophoresis of an iodinated spleen plasma-membrane fraction indicated peaks of radioactivity, including one of apparent mol.wt 110000-130000. 4. When detergent extracts of spleen lymphocytes were passed through a Sepharose-bead column containing covalently attached anti-(nucleotide pyrophosphatase) antiserum, the nucleotide pyrophosphatase activity was retained by the beads, whereas protein and leucine naphthylamidase activity were eluted. 5. The results indicate that nucleotide pyrophosphatase and alkaline phosphodiesterase activities are due to the location of the same or similar enzymes at the outer aspect of the lymphocyte plasma membrane. Some possible functions of enzymes at this location are discussed.", "contents": "Location of nucleotide pyrophosphatase and alkaline phosphodiesterase activities on the lymphocyte surface membrane. 1. Isolated mouse spleen lymphocytes hydrolysed UDP-galactose added to the medium. Nucleotide pyrophosphatase activity that accounted for this hydrolysis was enriched to a similar extent as alkaline phosphodiesterase and 5'-nucleotidase in a lymphocyte plasma-membrane fraction. 2. The cell surfaces of mouse spleen and thymus lymphocytes were iodinated with 125I by using the lactoperoxidase-catalysis method. Detergent extracts of the cells were mixed with a purified anti-(mouse liver plasma-membrane nucleotide pyrophosphatase) antiserum and the immunoprecipitates analysed by polyacrylamide-gel electrophoresis. Only one major radioactive component, similar in size (apparent mol.wt 110000-130000) to the liver enzyme, was observed. 3. Electrophoresis of an iodinated spleen plasma-membrane fraction indicated peaks of radioactivity, including one of apparent mol.wt 110000-130000. 4. When detergent extracts of spleen lymphocytes were passed through a Sepharose-bead column containing covalently attached anti-(nucleotide pyrophosphatase) antiserum, the nucleotide pyrophosphatase activity was retained by the beads, whereas protein and leucine naphthylamidase activity were eluted. 5. The results indicate that nucleotide pyrophosphatase and alkaline phosphodiesterase activities are due to the location of the same or similar enzymes at the outer aspect of the lymphocyte plasma membrane. Some possible functions of enzymes at this location are discussed."}
{"id": "PMID:187175", "title": "Purification and characterization of the catalytic subunit of adenosine 3':5'-cyclic monophosphate-dependent protein kinase from bovine liver.", "content": "1. The catalytic subunit of bovine liver cyclic AMP-dependent protein kinase (EC2.7.1.37) was purified essentially by the method of Reimann & Corbin [(1976) Fed. Proc. Fed. Am. Soc. Exp. Biol. 35, 1384]. 2. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, sedimentation-velocity centrifugation and sedimentation-equilibrium centrifugation showed that the catalytic subunit was monodisperse. Polyacrylamide-gel isoelectric-focusing electrophoresis revealed the presence of at least three isoenzyme forms of catalytic subunit activity with slightly different pI values (6.72, 7.04 and 7.35). 3. Physical properties of the catalytic subunit were determined by several different methods. It had mol.wt. 39000-42000, Stokes radium 2.73-3.08 nm, so20.w 3.14S, f/fo 1.19-1.23 and, assuming a prolate ellipsoid, axial ration 4-5. 4. Amino acid analysis was performed on the catalytic subunit. It had one cysteine residue/molecule which was essential for activity. Inhibition by thiol-specific reagents was partially prevented by the presence of ATP-Mg2+. 5. The circular-dichroic spectrum showed the catalytic subunit contained 29% alpha-helical form, 18% beta-form and 53% aperiodic form. Near-u.v. circular dichroism showed the presence of aromatic residues whose equivalent molar ellipticity was greatly altered by the addition of ATP-Mg2+. 6. Kinetic experiments showed that the catalytic subunit had an apparent Km for ATP of 7 muM. 5'-Adenylyl imidodiphosphate inhibitied competitively with ATP with a Ki of 60 muM. The kinetic plot for histone (Sigma, type II-A) was biphasic showing 'high'-and 'low'-Km segments. Under assay conditions the specific activity of the catalytic subunit was 3 X 10(6) units/mg of protein. Of various metal ions tested, the catalytic subunit was most active with Mg2+.7. When assayed with histone (Sigma, type II-A) as substrate, the activity of the catalytic subunit was increased by non-ionic detergents or urea. No such activation was observed with casein as substrate.", "contents": "Purification and characterization of the catalytic subunit of adenosine 3':5'-cyclic monophosphate-dependent protein kinase from bovine liver. 1. The catalytic subunit of bovine liver cyclic AMP-dependent protein kinase (EC2.7.1.37) was purified essentially by the method of Reimann & Corbin [(1976) Fed. Proc. Fed. Am. Soc. Exp. Biol. 35, 1384]. 2. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, sedimentation-velocity centrifugation and sedimentation-equilibrium centrifugation showed that the catalytic subunit was monodisperse. Polyacrylamide-gel isoelectric-focusing electrophoresis revealed the presence of at least three isoenzyme forms of catalytic subunit activity with slightly different pI values (6.72, 7.04 and 7.35). 3. Physical properties of the catalytic subunit were determined by several different methods. It had mol.wt. 39000-42000, Stokes radium 2.73-3.08 nm, so20.w 3.14S, f/fo 1.19-1.23 and, assuming a prolate ellipsoid, axial ration 4-5. 4. Amino acid analysis was performed on the catalytic subunit. It had one cysteine residue/molecule which was essential for activity. Inhibition by thiol-specific reagents was partially prevented by the presence of ATP-Mg2+. 5. The circular-dichroic spectrum showed the catalytic subunit contained 29% alpha-helical form, 18% beta-form and 53% aperiodic form. Near-u.v. circular dichroism showed the presence of aromatic residues whose equivalent molar ellipticity was greatly altered by the addition of ATP-Mg2+. 6. Kinetic experiments showed that the catalytic subunit had an apparent Km for ATP of 7 muM. 5'-Adenylyl imidodiphosphate inhibitied competitively with ATP with a Ki of 60 muM. The kinetic plot for histone (Sigma, type II-A) was biphasic showing 'high'-and 'low'-Km segments. Under assay conditions the specific activity of the catalytic subunit was 3 X 10(6) units/mg of protein. Of various metal ions tested, the catalytic subunit was most active with Mg2+.7. When assayed with histone (Sigma, type II-A) as substrate, the activity of the catalytic subunit was increased by non-ionic detergents or urea. No such activation was observed with casein as substrate."}
{"id": "PMID:187176", "title": "Interaction of pigeon-liver nicotinamide-adenine dinucleotide kinase with cibacron blue F3GA.", "content": "The interaction of pigeon liver NAD kinase with Cibacron Blue F3GA was investigated. By using steady-state rate measurements, spectrophotometric titration and chromatography of the enzyme on immobilized dye, it was shown that binding occurs at two nucleotide sites with different affinities, and also at a site distinct from the substrate-binding region.", "contents": "Interaction of pigeon-liver nicotinamide-adenine dinucleotide kinase with cibacron blue F3GA. The interaction of pigeon liver NAD kinase with Cibacron Blue F3GA was investigated. By using steady-state rate measurements, spectrophotometric titration and chromatography of the enzyme on immobilized dye, it was shown that binding occurs at two nucleotide sites with different affinities, and also at a site distinct from the substrate-binding region."}
{"id": "PMID:187205", "title": "The influence of theophylline on the motility and the cyclic 3',5'-AMP content in the pregnant and non-pregnant rat uterus in vitro.", "content": "The tension developed by muscle strips obtained from pregnant and non-pregnant rat uteri and uterine cyclic 3',5'-AMP was measured in the presence of increasing amounts of theophylline. In the pregnant uterus the initial tension was elevated by 112% and the tissue level of cAMP by 59% as compared to the normal organ. 1 mM theophylline relaxed the normal uterus by 81% and the pregnant uterus by 36% without any change in the cAMP concentrations. Higher amounts of theophylline (3-10 mM) able to relax the pregnant uterus completely also increased uterine cAMP in a dose dependent manner. It seems likely that the effect of high amounts of theophylline is mediated by cAMP, which, however, is not involved in the action of low (therapeutic) doses of the drug.", "contents": "The influence of theophylline on the motility and the cyclic 3',5'-AMP content in the pregnant and non-pregnant rat uterus in vitro. The tension developed by muscle strips obtained from pregnant and non-pregnant rat uteri and uterine cyclic 3',5'-AMP was measured in the presence of increasing amounts of theophylline. In the pregnant uterus the initial tension was elevated by 112% and the tissue level of cAMP by 59% as compared to the normal organ. 1 mM theophylline relaxed the normal uterus by 81% and the pregnant uterus by 36% without any change in the cAMP concentrations. Higher amounts of theophylline (3-10 mM) able to relax the pregnant uterus completely also increased uterine cAMP in a dose dependent manner. It seems likely that the effect of high amounts of theophylline is mediated by cAMP, which, however, is not involved in the action of low (therapeutic) doses of the drug."}
{"id": "PMID:187203", "title": "Lymphocyte response to virus antigens in systemic lupus erythematosus.", "content": "The cell-mediated immune response of lymphocytes to rubella, measles, parainfluenza types 1, 2, and 3, varicella-zoster and herpes virus type 1 virus antigens was evaluated in 15 SLE patients and 15 matched controls by incorporating 3H-thymidine in whole blood cultures as a measure of blastic transformation. SLE patients were less responsive than normal individuals to six of eight virus antigens tested. Culture of washed SLE cells in AB plasma did not reverse the hyporesponsiveness. The results indicated that a functional impairment of the circulating lymphocytes appeared to be responsible for the in vitro hyporesponsiveness of SLE patients to virus antigens.", "contents": "Lymphocyte response to virus antigens in systemic lupus erythematosus. The cell-mediated immune response of lymphocytes to rubella, measles, parainfluenza types 1, 2, and 3, varicella-zoster and herpes virus type 1 virus antigens was evaluated in 15 SLE patients and 15 matched controls by incorporating 3H-thymidine in whole blood cultures as a measure of blastic transformation. SLE patients were less responsive than normal individuals to six of eight virus antigens tested. Culture of washed SLE cells in AB plasma did not reverse the hyporesponsiveness. The results indicated that a functional impairment of the circulating lymphocytes appeared to be responsible for the in vitro hyporesponsiveness of SLE patients to virus antigens."}
{"id": "PMID:187207", "title": "Stimulation of anti-tumour immunity in guinea-pigs by methanol extraction residue of BCG.", "content": "The immunoprophylactic effects of the methanol extraction residue (MER) of BCG were investigated in Strain 2 guinea-pigs injected with cells of the transplantable, diethylnitrosamine-induced, Line 10 hepatocarcinoma. Pretreatment with MER at times ranging from 18 to 182 days prior to tumour implantation protected approximately 40% of guinea-pigs from progressive neoplastic disease. In addition, MER-treated animals developed specific cell-mediated anti-tumour immunity both more rapidly and at higher levels than did non-MER-treated tumour-bearing controls. It was not possible, however, to prognosticate from the results of such laboratory studies to the outcome of immunoprophylaxis.", "contents": "Stimulation of anti-tumour immunity in guinea-pigs by methanol extraction residue of BCG. The immunoprophylactic effects of the methanol extraction residue (MER) of BCG were investigated in Strain 2 guinea-pigs injected with cells of the transplantable, diethylnitrosamine-induced, Line 10 hepatocarcinoma. Pretreatment with MER at times ranging from 18 to 182 days prior to tumour implantation protected approximately 40% of guinea-pigs from progressive neoplastic disease. In addition, MER-treated animals developed specific cell-mediated anti-tumour immunity both more rapidly and at higher levels than did non-MER-treated tumour-bearing controls. It was not possible, however, to prognosticate from the results of such laboratory studies to the outcome of immunoprophylaxis."}
{"id": "PMID:187208", "title": "Hepatitis B surface antigen produced by a human hepatoma cell line.", "content": "The human hepatoma cell line, PLC/PRF/5, was shown to produce hepatitis B surface antigen (HBsAg). Immunologically reactive material was present in the supernatant tissue culture medium in significant amounts, and was associated with spherical particles approximately 20 nm in diameter. The rate of antigen production by the cells was estimated at 500 ng/day/10(6) cells by reference to a purified HBsAg standard. All immunological activity was neutralized by specific antibody and the subtype was ad. The studies reported here broaden the scope of investigations on both the in vitro production of HBsAg and the association between this antigen and primary liver cancer.", "contents": "Hepatitis B surface antigen produced by a human hepatoma cell line. The human hepatoma cell line, PLC/PRF/5, was shown to produce hepatitis B surface antigen (HBsAg). Immunologically reactive material was present in the supernatant tissue culture medium in significant amounts, and was associated with spherical particles approximately 20 nm in diameter. The rate of antigen production by the cells was estimated at 500 ng/day/10(6) cells by reference to a purified HBsAg standard. All immunological activity was neutralized by specific antibody and the subtype was ad. The studies reported here broaden the scope of investigations on both the in vitro production of HBsAg and the association between this antigen and primary liver cancer."}
{"id": "PMID:187209", "title": "Electron spin resonance study of changes during development of solid Yoshida tumour. I: Ascorbyl radical.", "content": "The ascorbyl radical concentration has been observed, by means of electron spin resonance spectroscopy, in the blood and spleen of female Wistar rats carrying a Yoshida tumour. The ascorbyl radical concentration of the tumour tissue itself was studied as the tumour was developing, and as it was regressing after treatment with methylene dimethane sulphonate. Changes in the concentration of this radical may be related to host tumour reactions.", "contents": "Electron spin resonance study of changes during development of solid Yoshida tumour. I: Ascorbyl radical. The ascorbyl radical concentration has been observed, by means of electron spin resonance spectroscopy, in the blood and spleen of female Wistar rats carrying a Yoshida tumour. The ascorbyl radical concentration of the tumour tissue itself was studied as the tumour was developing, and as it was regressing after treatment with methylene dimethane sulphonate. Changes in the concentration of this radical may be related to host tumour reactions."}
{"id": "PMID:187210", "title": "Electron spin resonance study of changes during development of solid yoshida tumour. II. Paramagnetic metal ions.", "content": "Electron spin resonance (ESR) spectroscopy was used to examine changes in the concentration of paramagnetic metal ions in Yoshida tumours carried by female Wistar rats. Blood, spleen and lymph nodes from these animals were also examined by ESR. A decrease in the concentration of a paramagnetic species associated with mitochondrial activity, and marked increases in those thought to be associated with inflammatory or immune reactions and cell lysis, were observed in the tumours within one day of implantation. During development of the tumour, and during its regression after treatment with methylene dimethane sulphonate (MDMS), further changes were observed in the concentration of the species. These were dependent on the region of the tumour examined. In blood, development of the tumour produced an increase in ceruloplasmin and a decrease in iron-transferrin. An increase in spleen weight, as the tumour developed, was accompanied by a small decrease in the concentration of species with g-values of 6-0 and 4-3, which was reversed on regression of the treated tumour. The presence of metastases in the regional lymph nodes produced distinguishable changes in the ESR spectra.", "contents": "Electron spin resonance study of changes during development of solid yoshida tumour. II. Paramagnetic metal ions. Electron spin resonance (ESR) spectroscopy was used to examine changes in the concentration of paramagnetic metal ions in Yoshida tumours carried by female Wistar rats. Blood, spleen and lymph nodes from these animals were also examined by ESR. A decrease in the concentration of a paramagnetic species associated with mitochondrial activity, and marked increases in those thought to be associated with inflammatory or immune reactions and cell lysis, were observed in the tumours within one day of implantation. During development of the tumour, and during its regression after treatment with methylene dimethane sulphonate (MDMS), further changes were observed in the concentration of the species. These were dependent on the region of the tumour examined. In blood, development of the tumour produced an increase in ceruloplasmin and a decrease in iron-transferrin. An increase in spleen weight, as the tumour developed, was accompanied by a small decrease in the concentration of species with g-values of 6-0 and 4-3, which was reversed on regression of the treated tumour. The presence of metastases in the regional lymph nodes produced distinguishable changes in the ESR spectra."}
{"id": "PMID:187212", "title": "Ribosomal-associated phosphatidylserine synthetase from Escherichia coli: purification by substrate-specific elution from phosphocellulose using cytidine 5'-diphospho-1,2-diacyl-sn-glycerol.", "content": "Cytidine 5'-diphospho-1,2-diacyl-sn-glycerol (CDPdiglyceride):L-serine O-phosphatidyltransferase (EC 2.7.8.8, phosphatidylserine synthetase) is bound tightly to the ribosomes in crude extracts of Escherichia coli. After separation of the enzyme from the ribosomes by the method of Raetz and Kennedy (Raetz, C.R.H., and Kennedy, E.P. (1974), J. Biol. Chem. 249, 5038), we have purified the enzyme to 97% of homogenekty. The major portion of the overall 5500-fold purification was attained by substrate-specific elution from phosphocellulose using CDP-diglyceride in the presence of detergent. The purified enzyme migrated as a single band with an apparent minimum molecular weight of 54 000 when subjected to electrophoresis on polyacrylamide disc gels containing sodium dodecyl sulfate. The purified enzyme catalyzed exchange reactions between cytidine 5'- monophosphate (CMP) and CDP-diglyceride and between serine and phosphatidylserine. The enzyme also catalyzed the hydrolysis of CDP-diglyceride to form CMP and phosphatidic acid. dCDP-diglyceride was equivalent to CDP-diglyceride in all reactions catalyzed by the enzyme. In addition, the purified enzyme catalyzed the formation of phosphatidylglycerol or phosphatidylglycerophosphate at a very slow rate when serine was replaced as substrate by glycerol or sn-glycero-3-phosphate, respectively. These results suggest catalysis occurs via a ping-pong mechanism through the formation of a phosphatidyl-enzyme intermediate.", "contents": "Ribosomal-associated phosphatidylserine synthetase from Escherichia coli: purification by substrate-specific elution from phosphocellulose using cytidine 5'-diphospho-1,2-diacyl-sn-glycerol. Cytidine 5'-diphospho-1,2-diacyl-sn-glycerol (CDPdiglyceride):L-serine O-phosphatidyltransferase (EC 2.7.8.8, phosphatidylserine synthetase) is bound tightly to the ribosomes in crude extracts of Escherichia coli. After separation of the enzyme from the ribosomes by the method of Raetz and Kennedy (Raetz, C.R.H., and Kennedy, E.P. (1974), J. Biol. Chem. 249, 5038), we have purified the enzyme to 97% of homogenekty. The major portion of the overall 5500-fold purification was attained by substrate-specific elution from phosphocellulose using CDP-diglyceride in the presence of detergent. The purified enzyme migrated as a single band with an apparent minimum molecular weight of 54 000 when subjected to electrophoresis on polyacrylamide disc gels containing sodium dodecyl sulfate. The purified enzyme catalyzed exchange reactions between cytidine 5'- monophosphate (CMP) and CDP-diglyceride and between serine and phosphatidylserine. The enzyme also catalyzed the hydrolysis of CDP-diglyceride to form CMP and phosphatidic acid. dCDP-diglyceride was equivalent to CDP-diglyceride in all reactions catalyzed by the enzyme. In addition, the purified enzyme catalyzed the formation of phosphatidylglycerol or phosphatidylglycerophosphate at a very slow rate when serine was replaced as substrate by glycerol or sn-glycero-3-phosphate, respectively. These results suggest catalysis occurs via a ping-pong mechanism through the formation of a phosphatidyl-enzyme intermediate."}
{"id": "PMID:187213", "title": "Kinetics of Novikoff cytoplasmic messenger RNA methylation.", "content": "Methylation patterns of Novikoff cytoplasmic mRNA were determined as a function of labeling time with L-[methyl-3H]methionine. The 5'-terminal m7G could be released from whole mRNA by treatment with nucleotide pyrophosphatase. Subsequent alkaline phosphatase treatment of this mRNA, followed by KOH digestion, yielded N'mpNp and N'mpNp from cap 1 (m7GpppN'mpN) and cap 2 (m7GpppN'mpN''mpN), respectively. Our results indicate that the relative amounts of labeled cap structures do change with time and that the amount of internal N6-methyladenosine decreases, relative to 5'-cap structures, as the cytoplasmic mRNAs age and the average size decreases. The formation of cap-2 structures by the addition of second 2'-O-methyl group at position N''m appears to be cytoplasmic event. Thus, after very short labeling times, greater than 80% of the labeled methyl groups in cap 2 are found in this position. These results, along with earlier data obtained on L-cell heterogeneous nuclear RNA methylation, are consistent with a model in which the nucleus is the cellular site of three mRNA methylation events producing 5'-terminal m7G, the first 2'-O-methylnucleoside (N'm) found in cap-1 structures and internal N6-methyladenosine. Subsequently, these nuclear methylations are followed by the cytoplasmic methylation at N''m. Analysis of the methynucleoside composition of cap-1 structures, along with comparable \"core\" structures (m7GpppN'm) generated from cap-2 by removal of N''m, indicates that at any single labeling time the methylnucleoside composition of a given cap-1 and the cap-2 \"core\" structure is remarkably similar. On the other hand, comparisons of the methylnucleoside composition of the cap structures at different labeling times indicate an increase in Cm in the first 2'-O-methylnucleoside (N'm) with time.", "contents": "Kinetics of Novikoff cytoplasmic messenger RNA methylation. Methylation patterns of Novikoff cytoplasmic mRNA were determined as a function of labeling time with L-[methyl-3H]methionine. The 5'-terminal m7G could be released from whole mRNA by treatment with nucleotide pyrophosphatase. Subsequent alkaline phosphatase treatment of this mRNA, followed by KOH digestion, yielded N'mpNp and N'mpNp from cap 1 (m7GpppN'mpN) and cap 2 (m7GpppN'mpN''mpN), respectively. Our results indicate that the relative amounts of labeled cap structures do change with time and that the amount of internal N6-methyladenosine decreases, relative to 5'-cap structures, as the cytoplasmic mRNAs age and the average size decreases. The formation of cap-2 structures by the addition of second 2'-O-methyl group at position N''m appears to be cytoplasmic event. Thus, after very short labeling times, greater than 80% of the labeled methyl groups in cap 2 are found in this position. These results, along with earlier data obtained on L-cell heterogeneous nuclear RNA methylation, are consistent with a model in which the nucleus is the cellular site of three mRNA methylation events producing 5'-terminal m7G, the first 2'-O-methylnucleoside (N'm) found in cap-1 structures and internal N6-methyladenosine. Subsequently, these nuclear methylations are followed by the cytoplasmic methylation at N''m. Analysis of the methynucleoside composition of cap-1 structures, along with comparable \"core\" structures (m7GpppN'm) generated from cap-2 by removal of N''m, indicates that at any single labeling time the methylnucleoside composition of a given cap-1 and the cap-2 \"core\" structure is remarkably similar. On the other hand, comparisons of the methylnucleoside composition of the cap structures at different labeling times indicate an increase in Cm in the first 2'-O-methylnucleoside (N'm) with time."}
{"id": "PMID:187214", "title": "Copper and the oxidation of hemoglobin: a comparison of horse and human hemoglobins.", "content": "Oxidation studies of hemoglobin by Cu(II) indicate that for horse hemoglobin, up to a Cu(II)/heme molar ratio of 0.5, all of the Cu(II) added is used to rapidly oxidize the heme. On the other hand, most of the Cu(II) added to human hemoglobin at low Cu(II)/heme molar ratios is unable to oxidize the heme. Only at Cu(II)/heme molar ratios greater than 0.5 does the amount of oxidation per added Cu(II) approach that of horse hemoglobin. At the same time, binding studies indicate that human hemoglobin has an additional binding site involving one copper for every two hemes, which has a higher copper affinity than the single horse hemoglobin binding site. The Cu(II) oxidation of human hemoglobin is explained utilizing this additional binding site by a mechanism where a transfer of electrons cannot occur between the heme and the Cu(II) bound to the high affinity human binding site. The electron transfer must involve the Cu(II) bound to the lower affinity human hemoglobin binding site, which is similar to the only horse hemoglobin site. The involvement of beta-2 histidine in the binding of this additional copper is indicated by a comparison of the amino acid sequences of various hemoglobins which possess the additional site, with the amino acid sequences of hemoglobins which do not possess the additional site. Zn(II), Hg(II), and N-ethylmaleimide (NEM) are found to decrease the Cu(II) oxidation of hemoglobin. The sulfhydryl reagents, Hg(II) and NEM, produce a very dramatic decrease in the rate of oxidation, which can only be explained by an effect on the rate for the actual transfer of electrons between the Cu(II) and the Fe(II). The effect of Zn(II) is much smaller and can, for the most part, be explained by the increased oxygen affinity, which affects the ligand dissociation process that must precede the electron transfer process.", "contents": "Copper and the oxidation of hemoglobin: a comparison of horse and human hemoglobins. Oxidation studies of hemoglobin by Cu(II) indicate that for horse hemoglobin, up to a Cu(II)/heme molar ratio of 0.5, all of the Cu(II) added is used to rapidly oxidize the heme. On the other hand, most of the Cu(II) added to human hemoglobin at low Cu(II)/heme molar ratios is unable to oxidize the heme. Only at Cu(II)/heme molar ratios greater than 0.5 does the amount of oxidation per added Cu(II) approach that of horse hemoglobin. At the same time, binding studies indicate that human hemoglobin has an additional binding site involving one copper for every two hemes, which has a higher copper affinity than the single horse hemoglobin binding site. The Cu(II) oxidation of human hemoglobin is explained utilizing this additional binding site by a mechanism where a transfer of electrons cannot occur between the heme and the Cu(II) bound to the high affinity human binding site. The electron transfer must involve the Cu(II) bound to the lower affinity human hemoglobin binding site, which is similar to the only horse hemoglobin site. The involvement of beta-2 histidine in the binding of this additional copper is indicated by a comparison of the amino acid sequences of various hemoglobins which possess the additional site, with the amino acid sequences of hemoglobins which do not possess the additional site. Zn(II), Hg(II), and N-ethylmaleimide (NEM) are found to decrease the Cu(II) oxidation of hemoglobin. The sulfhydryl reagents, Hg(II) and NEM, produce a very dramatic decrease in the rate of oxidation, which can only be explained by an effect on the rate for the actual transfer of electrons between the Cu(II) and the Fe(II). The effect of Zn(II) is much smaller and can, for the most part, be explained by the increased oxygen affinity, which affects the ligand dissociation process that must precede the electron transfer process."}
{"id": "PMID:187217", "title": "On the inhibitory activity of 4-vinyl analogues of pyridoxal: enzyme and cell culture studies.", "content": "Analogues of pyridoxal and of pyridoxal phosphate in which the 4-CHO group is replaced with CH = CH2 were synthesized and were found to be potent inhibitors of pyridoxal kinase and pyridoxine phosphate oxidase of rat liver. They also inhibited the growth of mouse Sarcoma 180 and mammary adenocarcinoma TA3 in cell culture. Saturation of the vinyl double bond, replacement of the 5-CH2OH with methyl, methylation of the phenolic hydroxyl, or conversion to the N-oxide resulted in diminution or loss of all these activities. Similarly, the introduction of a beta-methyl group into the vinyl analogues of pyridoxal reduced all these inhibitory activities. The 4-vinyl anatogue of pyridoxal was shown to be a substrate of pyridoxal kinase and the product a potent inhibitor of pyridoxine oxidase, competing with pyridoxal phosphate. The affinity of this phosphorylated pyridoxal analogue to some apoenzymes varied greatly, indicating striking differences among the cofactor binding sites of these enzymes. The growth inhibitory effects of these analogues on cells in culture correlated well with their effects on pyridoxal kinase and pyridoxine phosphate oxidase in cell-free systems.", "contents": "On the inhibitory activity of 4-vinyl analogues of pyridoxal: enzyme and cell culture studies. Analogues of pyridoxal and of pyridoxal phosphate in which the 4-CHO group is replaced with CH = CH2 were synthesized and were found to be potent inhibitors of pyridoxal kinase and pyridoxine phosphate oxidase of rat liver. They also inhibited the growth of mouse Sarcoma 180 and mammary adenocarcinoma TA3 in cell culture. Saturation of the vinyl double bond, replacement of the 5-CH2OH with methyl, methylation of the phenolic hydroxyl, or conversion to the N-oxide resulted in diminution or loss of all these activities. Similarly, the introduction of a beta-methyl group into the vinyl analogues of pyridoxal reduced all these inhibitory activities. The 4-vinyl anatogue of pyridoxal was shown to be a substrate of pyridoxal kinase and the product a potent inhibitor of pyridoxine oxidase, competing with pyridoxal phosphate. The affinity of this phosphorylated pyridoxal analogue to some apoenzymes varied greatly, indicating striking differences among the cofactor binding sites of these enzymes. The growth inhibitory effects of these analogues on cells in culture correlated well with their effects on pyridoxal kinase and pyridoxine phosphate oxidase in cell-free systems."}
{"id": "PMID:187218", "title": "Inhibition of estrogen-induced increases in uterine guanosine 3',5'-cyclic monophosphate levels by inhibitors of protein and RNA synthesis.", "content": "Uterine guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels are elevated significantly from 2 to 12 h after a single injection of estradiol-17 beta or diethylstilbestrol to mature, ovariectomized, or immature rats. The accumulation of cyclic GMP is greater in endometrial- than myometrial-enriched uterine tissue. The estrogen-induced increase in cyclic GMP can be prevented by administration of the protein synthesis inhibitors, cycloheximide and puromycin, or by relatively large doses of the RNA synthesis inhibitor, actinomycin D, but not by the muscarinic antagonist, atropine. The requirement for a protein with a relatively rapid rate of turnover is suggested by the demonstration that cycloheximide, when administered after estrogen, can within a 3-h period restore the estrogen-elevated levels of cyclic GMP to those of the non-estrogen-treated tissue.", "contents": "Inhibition of estrogen-induced increases in uterine guanosine 3',5'-cyclic monophosphate levels by inhibitors of protein and RNA synthesis. Uterine guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels are elevated significantly from 2 to 12 h after a single injection of estradiol-17 beta or diethylstilbestrol to mature, ovariectomized, or immature rats. The accumulation of cyclic GMP is greater in endometrial- than myometrial-enriched uterine tissue. The estrogen-induced increase in cyclic GMP can be prevented by administration of the protein synthesis inhibitors, cycloheximide and puromycin, or by relatively large doses of the RNA synthesis inhibitor, actinomycin D, but not by the muscarinic antagonist, atropine. The requirement for a protein with a relatively rapid rate of turnover is suggested by the demonstration that cycloheximide, when administered after estrogen, can within a 3-h period restore the estrogen-elevated levels of cyclic GMP to those of the non-estrogen-treated tissue."}
{"id": "PMID:187221", "title": "EPR and optical spectroscopic properties of the electron carrier intermediate between the reaction center bacteriochlorophylls and the primary acceptor in Chromatium vinosum.", "content": "1. A reaction center-cytochrome c complex has been isolated from Chromatium vinosum which is capable of normal photochemistry and light-activated rapid cytochrome c553 and c555 oxidation, but which has no antenna bacteriochlorophyll. As is found in whole cells, ferrocytochrome c553 is oxidized irreversibly in milliseconds by light at 7 K. 2. Room temperature redox potentiometry in combination with EPR analysis at 7 K, of cytochrome c553 and the reaction center bacteriochlorophyll dimer (BChl)2 absorbing at 883 nm yields identical results to those previously reported using optical analytical techniques at 77 K. It shows directly that two cytochrome c553 hemes are equivalent with respect to the light induced (BChl)2+. At 7 K, only one heme can be rapidly oxidized in the light, commensurate with the electron capacity of the primary acceptor (quinone-iron) being unity. 3. Prior chemical reduction of the quinone-iron followed by illumination at 200K, however, leads to the slow (t1/2 approximately equal to 30 s) oxidation of one cytochrome c553 heme, with what appears to be concommitant reduction of one of the two bacteriophytins (BPh) of the reaction center as shown by bleaching of the 760 nm band, a broad absorbance increase at approx. 650 nm and a bleaching at 543 nm. The 800 nm absorbing bacteriochlorophyll is also involved since there is also bleaching at 595 and 800 nm; at the latter wave-length the remaining unbleached band appears to shift significantly to the blue. No redox changes in the 883 absorbing bacteriochlorophyll dimer are seen during or after illumination under these conditions. The reduced part of the state represents what is considered to be the reduced form of the electron carrier (I) which acts as an intermediate between the bacteriochlorophyll dimer and quinone-iron. The state (oxidized c553/reduced I) relaxes in the dark at 200K in t1/2 approx. 20 min but below 77 K it is trapped on a days time scale. 4. EPR analysis of the state trapped as described above reveals that one heme equivalent of cytochrome becomes oxidized for the generation of the state, a result in agreement with the optical data. Two prominent signals are associated with the trapped state in the g = 2 region, which can be easily resolved with temperature and microwave power saturation: one has a line width of 15 g and is centered at g = 2.003; the other, which is the major signal, is also a radical centered at g = 2.003 but is split by 60 G and behaves as though it were an organic free-radical spin-coupled with another paramagnetic center absorbing at higher magnetic field values; this high field partner could be the iron-quinone of the primary acceptor. The identity of two signals associated with I-. is consistent with the idea that the reduced intermediary carrier is not simply BPh-. but also involves a second radical, perhaps the 800 nm bacteriochlorophylls in the reduced state...", "contents": "EPR and optical spectroscopic properties of the electron carrier intermediate between the reaction center bacteriochlorophylls and the primary acceptor in Chromatium vinosum. 1. A reaction center-cytochrome c complex has been isolated from Chromatium vinosum which is capable of normal photochemistry and light-activated rapid cytochrome c553 and c555 oxidation, but which has no antenna bacteriochlorophyll. As is found in whole cells, ferrocytochrome c553 is oxidized irreversibly in milliseconds by light at 7 K. 2. Room temperature redox potentiometry in combination with EPR analysis at 7 K, of cytochrome c553 and the reaction center bacteriochlorophyll dimer (BChl)2 absorbing at 883 nm yields identical results to those previously reported using optical analytical techniques at 77 K. It shows directly that two cytochrome c553 hemes are equivalent with respect to the light induced (BChl)2+. At 7 K, only one heme can be rapidly oxidized in the light, commensurate with the electron capacity of the primary acceptor (quinone-iron) being unity. 3. Prior chemical reduction of the quinone-iron followed by illumination at 200K, however, leads to the slow (t1/2 approximately equal to 30 s) oxidation of one cytochrome c553 heme, with what appears to be concommitant reduction of one of the two bacteriophytins (BPh) of the reaction center as shown by bleaching of the 760 nm band, a broad absorbance increase at approx. 650 nm and a bleaching at 543 nm. The 800 nm absorbing bacteriochlorophyll is also involved since there is also bleaching at 595 and 800 nm; at the latter wave-length the remaining unbleached band appears to shift significantly to the blue. No redox changes in the 883 absorbing bacteriochlorophyll dimer are seen during or after illumination under these conditions. The reduced part of the state represents what is considered to be the reduced form of the electron carrier (I) which acts as an intermediate between the bacteriochlorophyll dimer and quinone-iron. The state (oxidized c553/reduced I) relaxes in the dark at 200K in t1/2 approx. 20 min but below 77 K it is trapped on a days time scale. 4. EPR analysis of the state trapped as described above reveals that one heme equivalent of cytochrome becomes oxidized for the generation of the state, a result in agreement with the optical data. Two prominent signals are associated with the trapped state in the g = 2 region, which can be easily resolved with temperature and microwave power saturation: one has a line width of 15 g and is centered at g = 2.003; the other, which is the major signal, is also a radical centered at g = 2.003 but is split by 60 G and behaves as though it were an organic free-radical spin-coupled with another paramagnetic center absorbing at higher magnetic field values; this high field partner could be the iron-quinone of the primary acceptor. The identity of two signals associated with I-. is consistent with the idea that the reduced intermediary carrier is not simply BPh-. but also involves a second radical, perhaps the 800 nm bacteriochlorophylls in the reduced state..."}
{"id": "PMID:187222", "title": "Metabolism of pyridoxine in the liver of vitamin B-6-deficient rats.", "content": "The metabolism of [6-3H]pyridoxine - HCl was investigated in the liver of vitamin B-6-deficient rats. Rats were made vitamin B-6 deficient by feeding ad libitum for 42 days a diet lacking pyridoxine but otherwise optimal. Animals were each injected intraperitoneally with 33 muCi of [6-3H] pyridoxine - HCl and killed at different time intervals afterwards up to 7 days. Radioactively labeled hepatic B-6 compounds were extracted with acid and chromatographically separated on Dowex-X8 (H+) columns and the percent radioactivity for each vitamin compound was then calculated. Maximal uptake in control and deficient animals was observed 30 and 60 min, respectively, after administration of label. Radioactivity was not retained by the control animals but decreased steadily in a linear fashion after 30 min, reaching a low level after 3 h. On the other hand, vitamin deficient animals accumulated almost twice as much radioactivity in their liver as the controls and retained it through 7 days. In vitamin B-6 deficient animals 93% of the injected radioactivity was metabolized within 2 min at which time pyridoxine 5'-P and pyridoxal 5'-P reached 36 and 44% levels, respectively. Pyridoxine 5'-P dropped to minimal values (3%) within 15 min and remained unchanged for 7 days while pyridoxal 5'-P reached a peak (79%) level at 15 min and then began to drop linearly reaching a plateau (29%) at 5 days. Further, as the level of pyridoxal 5-P was falling, pyridoxamine 5'-P was linearly synthesized reaching a platuau low level (3%). The specific activity level of pyridoxal kinase decreased 3.2 times and that of pyridoxine 5'-phosphate oxidase increased 1.5 times in the state of deficiency. The results presented show that metabolism of [3H]pyridoxine in deficiency is characterized by (a) a delayed, two-fold increase in label uptake as well as an extended label retention period, (b) a rapid pyridoxal 5'-P synthesis, and (c) a continuous synthesis (and accumulation) of pyridoxamine 5'-P which is not utilized or further metabolized.", "contents": "Metabolism of pyridoxine in the liver of vitamin B-6-deficient rats. The metabolism of [6-3H]pyridoxine - HCl was investigated in the liver of vitamin B-6-deficient rats. Rats were made vitamin B-6 deficient by feeding ad libitum for 42 days a diet lacking pyridoxine but otherwise optimal. Animals were each injected intraperitoneally with 33 muCi of [6-3H] pyridoxine - HCl and killed at different time intervals afterwards up to 7 days. Radioactively labeled hepatic B-6 compounds were extracted with acid and chromatographically separated on Dowex-X8 (H+) columns and the percent radioactivity for each vitamin compound was then calculated. Maximal uptake in control and deficient animals was observed 30 and 60 min, respectively, after administration of label. Radioactivity was not retained by the control animals but decreased steadily in a linear fashion after 30 min, reaching a low level after 3 h. On the other hand, vitamin deficient animals accumulated almost twice as much radioactivity in their liver as the controls and retained it through 7 days. In vitamin B-6 deficient animals 93% of the injected radioactivity was metabolized within 2 min at which time pyridoxine 5'-P and pyridoxal 5'-P reached 36 and 44% levels, respectively. Pyridoxine 5'-P dropped to minimal values (3%) within 15 min and remained unchanged for 7 days while pyridoxal 5'-P reached a peak (79%) level at 15 min and then began to drop linearly reaching a plateau (29%) at 5 days. Further, as the level of pyridoxal 5-P was falling, pyridoxamine 5'-P was linearly synthesized reaching a platuau low level (3%). The specific activity level of pyridoxal kinase decreased 3.2 times and that of pyridoxine 5'-phosphate oxidase increased 1.5 times in the state of deficiency. The results presented show that metabolism of [3H]pyridoxine in deficiency is characterized by (a) a delayed, two-fold increase in label uptake as well as an extended label retention period, (b) a rapid pyridoxal 5'-P synthesis, and (c) a continuous synthesis (and accumulation) of pyridoxamine 5'-P which is not utilized or further metabolized."}
{"id": "PMID:187223", "title": "Phospholipid metabolism and lysosomal enzyme secretion by leukocytes. Effects of dibutyryl cyclic adenosine 3':5'-monophosphate and ATP.", "content": "The effects of dibutyryl cyclic adenosine 3':5'-monophosphate and ATP on isotope incorporation into phospholipids and the release of beta-glucuronidase into the extracellular medium were studied in polymorphonuclear leukocytes from guinea pig peritoneal exudates. Exogenous dibutyryl cyclic adenosine 3':5'-monophosphate (0.1--1.0 mM) reduced beta-glucoronidase release induced by cytochalasin B in the absence of inert particles. It selectively inhibited 32Pi incorporation into phosphatidic acid and the phosphoinositides and the incorporation of myo-[2-3H]inositol into the phosphoinositides. Added ATP (0.1--1.0 MM), but not other nucleotides, was found to potentiate beta-glucuronidase release provoked by cytochasin B, but it impaired the labeling of the phosphoinositides by myo-[2-3H]inositol. The mechanism of the inhibition the isotope incarparation into these acidic phospholipids by the two mucleotides has not been defined. Dibutyryl cyclic adenosine 3':5'-monophosphate at 2--4 mM concentration was not found to appreciably alter the incorporation of [gamma-32P]ATP into phosphatidic acid, phosphatidylinositol, diphosphoinositide, and triphosphoinositide.", "contents": "Phospholipid metabolism and lysosomal enzyme secretion by leukocytes. Effects of dibutyryl cyclic adenosine 3':5'-monophosphate and ATP. The effects of dibutyryl cyclic adenosine 3':5'-monophosphate and ATP on isotope incorporation into phospholipids and the release of beta-glucuronidase into the extracellular medium were studied in polymorphonuclear leukocytes from guinea pig peritoneal exudates. Exogenous dibutyryl cyclic adenosine 3':5'-monophosphate (0.1--1.0 mM) reduced beta-glucoronidase release induced by cytochalasin B in the absence of inert particles. It selectively inhibited 32Pi incorporation into phosphatidic acid and the phosphoinositides and the incorporation of myo-[2-3H]inositol into the phosphoinositides. Added ATP (0.1--1.0 MM), but not other nucleotides, was found to potentiate beta-glucuronidase release provoked by cytochasin B, but it impaired the labeling of the phosphoinositides by myo-[2-3H]inositol. The mechanism of the inhibition the isotope incarparation into these acidic phospholipids by the two mucleotides has not been defined. Dibutyryl cyclic adenosine 3':5'-monophosphate at 2--4 mM concentration was not found to appreciably alter the incorporation of [gamma-32P]ATP into phosphatidic acid, phosphatidylinositol, diphosphoinositide, and triphosphoinositide."}
{"id": "PMID:187224", "title": "Adenosine 3',5'cyclic monophosphate in adipose tissue of diabetic rats.", "content": "Normal male rats were made chronically diabetic by injection of alloxan or acutely diabetic by injection of anti-insulin serum. The concentration of cyclic AMP in epididymal adipose tissue was increased approximately 2 1/2-fold 24 h after alloxan administration and up to 7-fold 72 h post-alloxan. Treatment of alloxan-diabetic rats with insulin for 4 h completely suppressed lipolysis but only partially suppressed cyclic AMP levels; 6 h following insulin treatment cyclic AMP levels were normal. When segments of the epididymal fat bodies were incubated in vitro the high cyclic AMP levels were not maintained but instead decreased spontaneously. Addition of insulin to the incubation media decreased lipolysis in tissues of diabetic rats to levels measured in tissues of normal rats and accelerated the decline in cyclic AMP levels but did not return cyclic AMP levels to normal. Rats rendered acutely insulin deficient by injection of anti-insulin serum showed increased plasma glucose and free fatty acid levels and increased adipose tissue free fatty acid, and cyclic AMP levels 30 min following injection of the antiserum. Plasma glucagon levels increased but not until 2 h following anti-insulin serum, thereby excluding the possibility that an increment in plasma glucagon is the primary stimulus for the acceleration of lipolysis in diabetes. These data are consistent with the view that control of adipose tissue cyclic AMP levels in situ is an important physiologic action of insulin.", "contents": "Adenosine 3',5'cyclic monophosphate in adipose tissue of diabetic rats. Normal male rats were made chronically diabetic by injection of alloxan or acutely diabetic by injection of anti-insulin serum. The concentration of cyclic AMP in epididymal adipose tissue was increased approximately 2 1/2-fold 24 h after alloxan administration and up to 7-fold 72 h post-alloxan. Treatment of alloxan-diabetic rats with insulin for 4 h completely suppressed lipolysis but only partially suppressed cyclic AMP levels; 6 h following insulin treatment cyclic AMP levels were normal. When segments of the epididymal fat bodies were incubated in vitro the high cyclic AMP levels were not maintained but instead decreased spontaneously. Addition of insulin to the incubation media decreased lipolysis in tissues of diabetic rats to levels measured in tissues of normal rats and accelerated the decline in cyclic AMP levels but did not return cyclic AMP levels to normal. Rats rendered acutely insulin deficient by injection of anti-insulin serum showed increased plasma glucose and free fatty acid levels and increased adipose tissue free fatty acid, and cyclic AMP levels 30 min following injection of the antiserum. Plasma glucagon levels increased but not until 2 h following anti-insulin serum, thereby excluding the possibility that an increment in plasma glucagon is the primary stimulus for the acceleration of lipolysis in diabetes. These data are consistent with the view that control of adipose tissue cyclic AMP levels in situ is an important physiologic action of insulin."}
{"id": "PMID:187225", "title": "Effect of parathyroid hormone and cyclic AMP on protein phosphorylation in rabbit kidney cortex.", "content": "Suspensions of renal cortical tubules were incubated with 33Pi and exposed to parathyroid hormone (40 mlg/ml) or 1 mM dibutyryl cyclic AMP. In other experiments homogenates of renal cortex were assayed for protein kinase and phosphoprotein phosphatase activity using [gamma-32P]ATP with or without 5 mM cyclic AMP. Proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and phosphorylation of proteins measured by liquid scintillation counting of gel slices. The pattern of protein phosphorylation was similar in control tissue from both tubule suspensions and homogenates. In intact tubules, parathyroid hormone stimulated the phosphorylation of four proteins with molecular weights of approx. 150 000, 125 000, 100 000 and 50 000 by 28%, 24%, 13%, and 20%, respectively. Results with dibutyryl cyclic AMP were comparable but more variable. Stimulation of phosphorylation by cyclic AMP in homogenates was more generalized with the major effect on a 50 000 dalton protein (50% stimulation). No effect of cyclic AMP on dephosphorylation of proteins was observed. The results are interpreted as indicating that increased phosphorylation of cell proteins is part of the cyclic AMP-mediated response of the renal cortex to parathyroid hormone.", "contents": "Effect of parathyroid hormone and cyclic AMP on protein phosphorylation in rabbit kidney cortex. Suspensions of renal cortical tubules were incubated with 33Pi and exposed to parathyroid hormone (40 mlg/ml) or 1 mM dibutyryl cyclic AMP. In other experiments homogenates of renal cortex were assayed for protein kinase and phosphoprotein phosphatase activity using [gamma-32P]ATP with or without 5 mM cyclic AMP. Proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and phosphorylation of proteins measured by liquid scintillation counting of gel slices. The pattern of protein phosphorylation was similar in control tissue from both tubule suspensions and homogenates. In intact tubules, parathyroid hormone stimulated the phosphorylation of four proteins with molecular weights of approx. 150 000, 125 000, 100 000 and 50 000 by 28%, 24%, 13%, and 20%, respectively. Results with dibutyryl cyclic AMP were comparable but more variable. Stimulation of phosphorylation by cyclic AMP in homogenates was more generalized with the major effect on a 50 000 dalton protein (50% stimulation). No effect of cyclic AMP on dephosphorylation of proteins was observed. The results are interpreted as indicating that increased phosphorylation of cell proteins is part of the cyclic AMP-mediated response of the renal cortex to parathyroid hormone."}
{"id": "PMID:187226", "title": "Insulin degradation. XVIII. On the regulation of glutathione-insulin transhydrogenase in the hyperglycemic obese (ob/ob) mouse.", "content": "The occurrence of insulin-degrading activity in the liver of the obese hyperglycemic mouse (ob/ob) and its litter mate has been studied. The trichloroacetic acid-soluble product formed from insulin upon incubation with liver homogenate was identified as the A chain of insulin. In Ouchterlony double-diffusion experiments with antibody to purified rat liver glutathione-insulin transhydrogenase, mouse liver homogenate and the microsomal fraction each gave a single precipitation band of identity with the purified rat liver enzyme. These results indicate that the insulin-degrading activity present in the mouse liver is, in fact, glutathione-insulin transhydrogenase. Subcellular distribution studies of glutathione-insulin transhydrogenase and marker enzymes indicate that the transhydrogenase is located primarily in the microsomal fraction of mouse liver homogenate. The ob/ob mouse, which is a genetic mutant characterized by obesity, hyperinsulinism and resistance to the hypoglycemic action of insulin, contains hepatic glutathione-insulin transhydrogenase activity (per mg microsomal protein) markedly higher (40--60%) than its lean litter mates. However, a major portion of the increased hepatic enzyme in the ob/ob mouse occurs in a latent state; the increased amount of enzyme either is unavailable or is nonfunctional, although the ob/ob mouse still contains more of the functional form than the lean mouse. Thus, the results are consistent with the suggestion that the hepatic glutathione-insulin transhydrogenase is probably under a feedback control by circulating insulin.", "contents": "Insulin degradation. XVIII. On the regulation of glutathione-insulin transhydrogenase in the hyperglycemic obese (ob/ob) mouse. The occurrence of insulin-degrading activity in the liver of the obese hyperglycemic mouse (ob/ob) and its litter mate has been studied. The trichloroacetic acid-soluble product formed from insulin upon incubation with liver homogenate was identified as the A chain of insulin. In Ouchterlony double-diffusion experiments with antibody to purified rat liver glutathione-insulin transhydrogenase, mouse liver homogenate and the microsomal fraction each gave a single precipitation band of identity with the purified rat liver enzyme. These results indicate that the insulin-degrading activity present in the mouse liver is, in fact, glutathione-insulin transhydrogenase. Subcellular distribution studies of glutathione-insulin transhydrogenase and marker enzymes indicate that the transhydrogenase is located primarily in the microsomal fraction of mouse liver homogenate. The ob/ob mouse, which is a genetic mutant characterized by obesity, hyperinsulinism and resistance to the hypoglycemic action of insulin, contains hepatic glutathione-insulin transhydrogenase activity (per mg microsomal protein) markedly higher (40--60%) than its lean litter mates. However, a major portion of the increased hepatic enzyme in the ob/ob mouse occurs in a latent state; the increased amount of enzyme either is unavailable or is nonfunctional, although the ob/ob mouse still contains more of the functional form than the lean mouse. Thus, the results are consistent with the suggestion that the hepatic glutathione-insulin transhydrogenase is probably under a feedback control by circulating insulin."}
{"id": "PMID:187227", "title": "Independent modulation of hepatic protein kinase activities.", "content": "The effects of hormonal status on protein kinase activity was examined in homogenates of rat liver. Protein kinase activity was evaluated from incorporation of 32P from [gamma-32P]ATP into protamine or histone as receptor substrates. Protamine phosphorylation in the presence or absence of cyclic AMP exceeded histone phosphorylation by at least a factor or two. Hypophysectomy markedly increased protamine phosphorylation in the presence or absence of saturating amounts of cyclic AMP. In contrast, hypophysectomy only slightly increased cyclic AMP independent phosphorylation of histone. These results could not be amounted for by differences in ATPase or protein phosphase activities. Cortisone (2 mg/day x 3) decreased total protein kinase activity in livers of hypophysectomized rats when protamine was substrate, but had no effect on the total activity toward histone. Growth hormone (100 mug/day x 3) significantly increased histone, but not protamine phosphorylation in livers of hypophysectomized rats. Administration of 5 mug of triiodothyonine/day to hypophysectomized rats also markedly increased the phosphorylation of histone, but not protamine when saturating amounts of cyclic AMP were present. These results support the hypothesis that liver may contain more than one type of protein kinase activity and that the different protein kinase activities can be separately affected by hormones. Such control distal to cyclic AMP might allow selective modulation of cyclic AMP-dependent processes in cells which carry out more than one such process.", "contents": "Independent modulation of hepatic protein kinase activities. The effects of hormonal status on protein kinase activity was examined in homogenates of rat liver. Protein kinase activity was evaluated from incorporation of 32P from [gamma-32P]ATP into protamine or histone as receptor substrates. Protamine phosphorylation in the presence or absence of cyclic AMP exceeded histone phosphorylation by at least a factor or two. Hypophysectomy markedly increased protamine phosphorylation in the presence or absence of saturating amounts of cyclic AMP. In contrast, hypophysectomy only slightly increased cyclic AMP independent phosphorylation of histone. These results could not be amounted for by differences in ATPase or protein phosphase activities. Cortisone (2 mg/day x 3) decreased total protein kinase activity in livers of hypophysectomized rats when protamine was substrate, but had no effect on the total activity toward histone. Growth hormone (100 mug/day x 3) significantly increased histone, but not protamine phosphorylation in livers of hypophysectomized rats. Administration of 5 mug of triiodothyonine/day to hypophysectomized rats also markedly increased the phosphorylation of histone, but not protamine when saturating amounts of cyclic AMP were present. These results support the hypothesis that liver may contain more than one type of protein kinase activity and that the different protein kinase activities can be separately affected by hormones. Such control distal to cyclic AMP might allow selective modulation of cyclic AMP-dependent processes in cells which carry out more than one such process."}
{"id": "PMID:187228", "title": "The development of phosphomonesterases in the testes of prepuberal chicks.", "content": "1. The biochemical development and histochemical localisation of phosphomonoesterases in the testes of prepuberal chicks have been studied. 2. Maximum acid phosphatase activity was observed at 12 weeks with a decrease in enzyme activity after this age, whereas alkaline phosphatase activity fluctuated with age. 3. Acid phosphatase activity in chicks was similar to that of the cockerel in being tartarate-insensitive. 4. There was a low level of significant correlation between acid phosphatase activity and testes weight. 5. Both alkaline and acid phosphatase activities were observed in the basement membrane of the seminiferous tubules, and acid phosphatase activity also in the various spermatogenic elements. 6. The results suggest that acid phosphatase is more involved in spermatogenesis, and more widely distributed than alkaline phosphatase in testicular tissue during testicular development.", "contents": "The development of phosphomonesterases in the testes of prepuberal chicks. 1. The biochemical development and histochemical localisation of phosphomonoesterases in the testes of prepuberal chicks have been studied. 2. Maximum acid phosphatase activity was observed at 12 weeks with a decrease in enzyme activity after this age, whereas alkaline phosphatase activity fluctuated with age. 3. Acid phosphatase activity in chicks was similar to that of the cockerel in being tartarate-insensitive. 4. There was a low level of significant correlation between acid phosphatase activity and testes weight. 5. Both alkaline and acid phosphatase activities were observed in the basement membrane of the seminiferous tubules, and acid phosphatase activity also in the various spermatogenic elements. 6. The results suggest that acid phosphatase is more involved in spermatogenesis, and more widely distributed than alkaline phosphatase in testicular tissue during testicular development."}
{"id": "PMID:187229", "title": "Disaggregation of hydroxyapatite crystals.", "content": "A system has been developed to measure quantitatively the disaggregation of hydroxyapatite crystals. Disaggregation was induced by pyrophosphate, ethane-1-hydroxy-1,1-diphosphonate, dichloromethylene diphosphonate, haparin and citrate. Hyaluronic acid stimulated aggregation at low concentrations and disaggregation at high concentrations. Lactate had no effect. The possible role disaggregation might play in the resorption of calcified tissues in vivo id discussed.", "contents": "Disaggregation of hydroxyapatite crystals. A system has been developed to measure quantitatively the disaggregation of hydroxyapatite crystals. Disaggregation was induced by pyrophosphate, ethane-1-hydroxy-1,1-diphosphonate, dichloromethylene diphosphonate, haparin and citrate. Hyaluronic acid stimulated aggregation at low concentrations and disaggregation at high concentrations. Lactate had no effect. The possible role disaggregation might play in the resorption of calcified tissues in vivo id discussed."}
{"id": "PMID:187230", "title": "Absorption and circular dichroism spectra of different forms of mushroom tyrosinase.", "content": "The circular dichroism spectrum of resting mushroom tyrosinase between 800 and 400 nm showed two bands at 755, and 653 nm. The CD spectrum of resting tyrosinase between 400 and 250 nm showed oxygen-sensitive changes at 350 nm upon treatment of tyrosinase with hydroxylamine or hydrogen peroxide. These were similar to changes observed on regeneration of aged hemocyanin by similar procedures. A structural relationship between the active sites of hydroxylamine- or hydrogen peroxide-treated tyrosinase and hemocyanin is suggested by these observations, confirming inferences based upon other studies (Jolly, Jr., R.L., Evans, L.H., Makino, N. and Mason, H.S. (1974) J. Biol. Chem. 249, 335-345 and Schoot Uiterkamp, A.J.M. and Mason, H.S. (1973) Proc. Natl. Acad, Sci. U.S. 70, 993-996).", "contents": "Absorption and circular dichroism spectra of different forms of mushroom tyrosinase. The circular dichroism spectrum of resting mushroom tyrosinase between 800 and 400 nm showed two bands at 755, and 653 nm. The CD spectrum of resting tyrosinase between 400 and 250 nm showed oxygen-sensitive changes at 350 nm upon treatment of tyrosinase with hydroxylamine or hydrogen peroxide. These were similar to changes observed on regeneration of aged hemocyanin by similar procedures. A structural relationship between the active sites of hydroxylamine- or hydrogen peroxide-treated tyrosinase and hemocyanin is suggested by these observations, confirming inferences based upon other studies (Jolly, Jr., R.L., Evans, L.H., Makino, N. and Mason, H.S. (1974) J. Biol. Chem. 249, 335-345 and Schoot Uiterkamp, A.J.M. and Mason, H.S. (1973) Proc. Natl. Acad, Sci. U.S. 70, 993-996)."}
{"id": "PMID:187231", "title": "Low temperature magnetic susceptibility of a human Co(II) carbonic anhydrase B sulphonamide complex.", "content": "The magnetic susceptibility of the acetazolamide complex of human Co(II) carbonic anhydrase B was measured between 1.4 and 160 K. From the temperature dependence of the paramagnetic contribution of Co(II) a g-value of 2.23 +/- 0.02 and a zero-field splitting of (33 +/- 1) cm-1 were estimated. The effective number of Bohr magnetons as T leads to 0 is 3.35 in excellent agreement with the number (3.38) calculated from the apparent g'-values of the EPR spectrum at 16 K. Extrapolation to high temperatures gave an effective number of Bohr magnetons of 4.32.", "contents": "Low temperature magnetic susceptibility of a human Co(II) carbonic anhydrase B sulphonamide complex. The magnetic susceptibility of the acetazolamide complex of human Co(II) carbonic anhydrase B was measured between 1.4 and 160 K. From the temperature dependence of the paramagnetic contribution of Co(II) a g-value of 2.23 +/- 0.02 and a zero-field splitting of (33 +/- 1) cm-1 were estimated. The effective number of Bohr magnetons as T leads to 0 is 3.35 in excellent agreement with the number (3.38) calculated from the apparent g'-values of the EPR spectrum at 16 K. Extrapolation to high temperatures gave an effective number of Bohr magnetons of 4.32."}
{"id": "PMID:187232", "title": "A study of the enzymic dephosphorylation of beta-casein and a derived phosphopeptide.", "content": "beta-Casein, and the phosphate containing peptide derived from it by tryptic digestion, have been dephosphorylated by the action of two phosphatases. Escherichia coli alkaline phosphatase (EC 3.1.3.1) has been shown to remove the phosphates from these substrates in two distinct stages. Substrate molecules retaining three of the original phosphoseryl residues accumulate during the reaction and are resistant to further dephosphorylation at low enzyme concentrations. In contrast bovine spleen phosphoprotein phosphatase (EC 3.1.3.16) achieves complete dephosphorylation of these substrates sequentially without any of the intervening species showing resistance to the action of the enzyme. The phosphopeptide has been partially dephosphorylated by the action of the two phosphatases and the resultant peptides containing three phosphoseryl residues compared in their reactivity toward the E. coli alkaline phosphatase. The results obtained are discussed in relation to the mode of action of the two enzymes.", "contents": "A study of the enzymic dephosphorylation of beta-casein and a derived phosphopeptide. beta-Casein, and the phosphate containing peptide derived from it by tryptic digestion, have been dephosphorylated by the action of two phosphatases. Escherichia coli alkaline phosphatase (EC 3.1.3.1) has been shown to remove the phosphates from these substrates in two distinct stages. Substrate molecules retaining three of the original phosphoseryl residues accumulate during the reaction and are resistant to further dephosphorylation at low enzyme concentrations. In contrast bovine spleen phosphoprotein phosphatase (EC 3.1.3.16) achieves complete dephosphorylation of these substrates sequentially without any of the intervening species showing resistance to the action of the enzyme. The phosphopeptide has been partially dephosphorylated by the action of the two phosphatases and the resultant peptides containing three phosphoseryl residues compared in their reactivity toward the E. coli alkaline phosphatase. The results obtained are discussed in relation to the mode of action of the two enzymes."}
{"id": "PMID:187233", "title": "The effect of phospholipase C on DNA synthesis, morphology and phospholipid content of isolated HeLa cell nuclei.", "content": "Isolated HeLa cell nuclei have been treated with purified phospholipase C (Bacillus cereus) and sphingomyelinase (Staphylococcus aureus). The phospholipids of untreated nuclei consisted of about 67% phosphatidylcholine, 23% phosphatidylethanolamine, 7% sphingomyelin, 2% phosphatidylserine and 1% phosphatidylinositol. Phospholipase C degraded 80-90% of the total phospholipids of the nuclei. Such nuclei seemed ultrastructurally intact, and had an average diameter and a protein loss during incubation which were not significantly different from those of controls. Their rate of DNA synthesis was only slightly reduced after treatment with phospholipase C alone and slightly more reduced when phospholipase C was used in combination with sphingomyelinase. This suggests that the polar head-groups of the nuclear phospholipids are of very limited importance in DNA synthesis. Since it has been reported that phospholipase C treatment releases nascent DNA from a membrane complex, the absence of a concommitant reduction in DNA synthesis may suggest that this complex is not necessary for the replication of DNA. Phospholipase C did not significantly influence the stability of the DNA product and gave only a slight inhibition of cytosol and nuclear DNA polymerases when tested with exogenous template.", "contents": "The effect of phospholipase C on DNA synthesis, morphology and phospholipid content of isolated HeLa cell nuclei. Isolated HeLa cell nuclei have been treated with purified phospholipase C (Bacillus cereus) and sphingomyelinase (Staphylococcus aureus). The phospholipids of untreated nuclei consisted of about 67% phosphatidylcholine, 23% phosphatidylethanolamine, 7% sphingomyelin, 2% phosphatidylserine and 1% phosphatidylinositol. Phospholipase C degraded 80-90% of the total phospholipids of the nuclei. Such nuclei seemed ultrastructurally intact, and had an average diameter and a protein loss during incubation which were not significantly different from those of controls. Their rate of DNA synthesis was only slightly reduced after treatment with phospholipase C alone and slightly more reduced when phospholipase C was used in combination with sphingomyelinase. This suggests that the polar head-groups of the nuclear phospholipids are of very limited importance in DNA synthesis. Since it has been reported that phospholipase C treatment releases nascent DNA from a membrane complex, the absence of a concommitant reduction in DNA synthesis may suggest that this complex is not necessary for the replication of DNA. Phospholipase C did not significantly influence the stability of the DNA product and gave only a slight inhibition of cytosol and nuclear DNA polymerases when tested with exogenous template."}
{"id": "PMID:187234", "title": "Selenalysine and protein synthesis.", "content": "Selenalysine is a lysine analog having the gamma-methylene group substituted by a selenium atom. It has been demonstrated that selenalysine is activated and transferred to tRNAlys by either Escherichia coli or rat liver aminoacyl-tRNA synthetases, and inhibits lysine incorporation into polypeptides in protein-synthesizing systems from E. coli, rat liver or rabbit reticulocytes. All tests were performed in comparison with thialysine, a lysine analog having the gamma-methylene group substituted by a sulfur atom. In all the reactions studied, both thialysine and selenalysine act as competitive inhibitors of lysine. With respect to thialysine, selenalysine act as competitive inhibitors of lysine. With respect to thialysine, selenalysine shows a slightly lower activity as lysine inhibitor.", "contents": "Selenalysine and protein synthesis. Selenalysine is a lysine analog having the gamma-methylene group substituted by a selenium atom. It has been demonstrated that selenalysine is activated and transferred to tRNAlys by either Escherichia coli or rat liver aminoacyl-tRNA synthetases, and inhibits lysine incorporation into polypeptides in protein-synthesizing systems from E. coli, rat liver or rabbit reticulocytes. All tests were performed in comparison with thialysine, a lysine analog having the gamma-methylene group substituted by a sulfur atom. In all the reactions studied, both thialysine and selenalysine act as competitive inhibitors of lysine. With respect to thialysine, selenalysine act as competitive inhibitors of lysine. With respect to thialysine, selenalysine shows a slightly lower activity as lysine inhibitor."}
{"id": "PMID:187235", "title": "Characterization of the 3'-terminal region of the large molecular weight RNA subunits from normal and transformation-defective Rous sarcoma virus.", "content": "In avian sarcoma viruses a function required to transform cells is frequently lost giving rise to non-transforming virus. The genetic information for this function is localized near the 3' end of the genome. Short 3'-terminal poly(A)-linked RNA fragments from the genomes of a transforming Rous sarcoma virus and its non-transforming derivative were isolated and gave rise to identical fingerprint patterns, suggesting that internal deletion rather than terminal elimination leads to non-transforming virus.", "contents": "Characterization of the 3'-terminal region of the large molecular weight RNA subunits from normal and transformation-defective Rous sarcoma virus. In avian sarcoma viruses a function required to transform cells is frequently lost giving rise to non-transforming virus. The genetic information for this function is localized near the 3' end of the genome. Short 3'-terminal poly(A)-linked RNA fragments from the genomes of a transforming Rous sarcoma virus and its non-transforming derivative were isolated and gave rise to identical fingerprint patterns, suggesting that internal deletion rather than terminal elimination leads to non-transforming virus."}
{"id": "PMID:187236", "title": "Comparison of DNA facilitators in the uptake and intracellular fate of infectious herpes simplex virus type 2 DNA.", "content": "The comparative efficiencies of polyornithine, CaCl2 and DEAE-dextran in enhancing the infectivity of exogenous herpes simplex virus (HSV) type 2 DNA were examined. CaCl2 was 12-times more effective in promoting genetic expression of viral DNA than DEAE-dextran, while polyornithine did not mediate any HSV DNA infectivity. A comparison of sedimentation profiles of DNA extracted from cells inoculated with viral DNA in the presence of each facilitator revealed that input 56 S HSV DNA underwent marked alteration with time. There was also extensive processing of a 20 S DNA species. The data indicated that the biological efficiency of each facilitator was related to the amount of 20 S DNA remaining at the final time periods. One possible explanation for the efficiency of CaCl2 as a facilitator was that it allowed for the reutilization of the 20 S DNA species during HSV replication. The persistence of the 20 S peak in cells treated with DEAE-dextran was a measure of the decreased efficacy of this facilitator. Finally, the absence of a 56 S peak and the greatly elevated levels of 20 S DNA at final time points in polyornithine-treated cells accounted for the failure of this compound to promote HSV DNA infectivity.", "contents": "Comparison of DNA facilitators in the uptake and intracellular fate of infectious herpes simplex virus type 2 DNA. The comparative efficiencies of polyornithine, CaCl2 and DEAE-dextran in enhancing the infectivity of exogenous herpes simplex virus (HSV) type 2 DNA were examined. CaCl2 was 12-times more effective in promoting genetic expression of viral DNA than DEAE-dextran, while polyornithine did not mediate any HSV DNA infectivity. A comparison of sedimentation profiles of DNA extracted from cells inoculated with viral DNA in the presence of each facilitator revealed that input 56 S HSV DNA underwent marked alteration with time. There was also extensive processing of a 20 S DNA species. The data indicated that the biological efficiency of each facilitator was related to the amount of 20 S DNA remaining at the final time periods. One possible explanation for the efficiency of CaCl2 as a facilitator was that it allowed for the reutilization of the 20 S DNA species during HSV replication. The persistence of the 20 S peak in cells treated with DEAE-dextran was a measure of the decreased efficacy of this facilitator. Finally, the absence of a 56 S peak and the greatly elevated levels of 20 S DNA at final time points in polyornithine-treated cells accounted for the failure of this compound to promote HSV DNA infectivity."}
{"id": "PMID:187237", "title": "The effects of glucose and cyclic GMP on RNA synthesis and nuclear morphology in starved rats.", "content": "Feeding rats in diet high in glucose has been demonstrated to inhibit the induction of many enzymes, block the action of glucocorticoids, and, in general, appears to result in decreased cyclic AMP activity. We found that glucose feeding depresses both messenger RNA (mRNA) and non-mRNA synthesis. Electron microscopic examination of the nucleus revealed that glucose feeding decreases the granular component of liver cell nucleoli. It only slightly decreases liver cyclic AMP levels, but produces a sixfold elevation in levels of the cyclic AMP antagonist, cyclic GMP. Administration of bromocyclic GMP, like glucose feeding, depresses mRNA synthesis, but does not simulate the effect of the carbohydrate on nuclear morphology. In addition, glucose feeding halves liver inorganic phosphate and triples ATP levels. Phosphorylation of nuclear proteins, however, remains unaltered. Despite the antagonism between glucose feeding and glucocorticoid activity, the former compound did not change the binding of dexamethasone to liver nuclei.", "contents": "The effects of glucose and cyclic GMP on RNA synthesis and nuclear morphology in starved rats. Feeding rats in diet high in glucose has been demonstrated to inhibit the induction of many enzymes, block the action of glucocorticoids, and, in general, appears to result in decreased cyclic AMP activity. We found that glucose feeding depresses both messenger RNA (mRNA) and non-mRNA synthesis. Electron microscopic examination of the nucleus revealed that glucose feeding decreases the granular component of liver cell nucleoli. It only slightly decreases liver cyclic AMP levels, but produces a sixfold elevation in levels of the cyclic AMP antagonist, cyclic GMP. Administration of bromocyclic GMP, like glucose feeding, depresses mRNA synthesis, but does not simulate the effect of the carbohydrate on nuclear morphology. In addition, glucose feeding halves liver inorganic phosphate and triples ATP levels. Phosphorylation of nuclear proteins, however, remains unaltered. Despite the antagonism between glucose feeding and glucocorticoid activity, the former compound did not change the binding of dexamethasone to liver nuclei."}
{"id": "PMID:187238", "title": "Characterization of a protein kinase-phosphoprotein system in free cytoplasmic ribonucleoprotein particles of plasma cell tumours.", "content": "A protein kinase, associated with free cytoplasmic ribonucleoprotein particles (free dRNP) has been purified from mouse plasma cell tumours. This protein kinase is able to phosphorylate in vitro endogenous protein from free dRNP. Some characteristics of this protein kinase have been studied. This protein kinase behaves as being cyclic AMP independent. The properties of this protein kinase were compared with other protein kinases: soluble, ribosome-bound, and nuclear protein kinases. Although there are minor differences it is very similar to a ribosome-associated protein kinase from the plasma cell tumours.", "contents": "Characterization of a protein kinase-phosphoprotein system in free cytoplasmic ribonucleoprotein particles of plasma cell tumours. A protein kinase, associated with free cytoplasmic ribonucleoprotein particles (free dRNP) has been purified from mouse plasma cell tumours. This protein kinase is able to phosphorylate in vitro endogenous protein from free dRNP. Some characteristics of this protein kinase have been studied. This protein kinase behaves as being cyclic AMP independent. The properties of this protein kinase were compared with other protein kinases: soluble, ribosome-bound, and nuclear protein kinases. Although there are minor differences it is very similar to a ribosome-associated protein kinase from the plasma cell tumours."}
{"id": "PMID:187239", "title": "Plasma membrane studies on drug-sensitive and -resistant cell lines. II. Ouabain sensitivity of (Na+ +K+)-stimulated Mg2+-ATPase.", "content": "Mutant cell lines have been selected from the murine plasmocytoma MOPC 173 for their resistance to ouabain, dibutyryl cyclic AMP, theophyllin and concanavalin A. We have compared three wild-type cell lines with their seven resistant counterparts. All resistant mutants exhibited a (Na+ + K+)-stimulated Mg2+-ATPase resistance to ouabain inhibition when measured in microsomes. The homogeneity of ouabain binding sites has been found in most of the cell lines; however, two different populations of sites have been detected in one wild-type and in one resistant cell lines. These results led us to hypothetise the (Na+ + K+)-ATPase-ouabain interaction being modulated by a non-specific membrane structure.", "contents": "Plasma membrane studies on drug-sensitive and -resistant cell lines. II. Ouabain sensitivity of (Na+ +K+)-stimulated Mg2+-ATPase. Mutant cell lines have been selected from the murine plasmocytoma MOPC 173 for their resistance to ouabain, dibutyryl cyclic AMP, theophyllin and concanavalin A. We have compared three wild-type cell lines with their seven resistant counterparts. All resistant mutants exhibited a (Na+ + K+)-stimulated Mg2+-ATPase resistance to ouabain inhibition when measured in microsomes. The homogeneity of ouabain binding sites has been found in most of the cell lines; however, two different populations of sites have been detected in one wild-type and in one resistant cell lines. These results led us to hypothetise the (Na+ + K+)-ATPase-ouabain interaction being modulated by a non-specific membrane structure."}
{"id": "PMID:187240", "title": "Comparison of the epinephrine-mediated activation of adenylate cyclase in plasma membranes from liver and ascites hepatomas of rats.", "content": "(1) The apparent [3H]epinephrine binding parameters of plasma membranes from rat liver and ascites hepatomas such as AH-7974, AH-371A and AH-130, as measured by equilibrium dialysis and/or Millipore filtration, were almost similar to each other. The epinephrine binding sites in the plasma membranes were heterogenous (alpha, beta-receptors and non specific sites), but the pattern of these binding sites in the liver membranes appeared almost similar to that in the hepatoma membranes. 2. The beta-receptor seemed to be specifically involved in the epinephrine-mediated activation of adenylate cyclase of the liver membranes. In spite of the presence of almost similar beta-receptors and adenylate cyclase, the adenylate cyclase of hepatoma membranes was found to be less sensitive to the epinephrine-mediated activation. 3. GTP alone was found to activate adenylate cyclase of liver and hepatoma membranes to some extents when the concentration of ATP was lower (0.3 mM). When GTP was added with epinephrine, a marked, synergistic activation of adenylate cyclase was observed in liver plasma membranes, but not in hepatoma ones. 4. The synergistic activation of adenylate cyclase by epinephrine plus GTP showed a characteristic kinetic feature, reaching a maximal peak within 1 min or so after mixing. 5. Binding of [3H]epinephrine to liver membranes proceeded monophasically in the absence of GTP, while it proceeded biphasically in the presence of GTP, showing the retardation of binding at some earlier stages. GTP added at the time of binding equilibrium induced the temporary release of bound epinephrine from the beta-receptors. The GTP-induced temporary release of bound epinephrine, occurring within 4-5 min after the addition of GTP, was less marked in the hepatoma membranes as compared with the liver membranes. 6. Possible impairment of the GTP-dependent coupling mechanism in the receptor-adenylate cyclase system of hepatoma plasma membranes was suggested.", "contents": "Comparison of the epinephrine-mediated activation of adenylate cyclase in plasma membranes from liver and ascites hepatomas of rats. (1) The apparent [3H]epinephrine binding parameters of plasma membranes from rat liver and ascites hepatomas such as AH-7974, AH-371A and AH-130, as measured by equilibrium dialysis and/or Millipore filtration, were almost similar to each other. The epinephrine binding sites in the plasma membranes were heterogenous (alpha, beta-receptors and non specific sites), but the pattern of these binding sites in the liver membranes appeared almost similar to that in the hepatoma membranes. 2. The beta-receptor seemed to be specifically involved in the epinephrine-mediated activation of adenylate cyclase of the liver membranes. In spite of the presence of almost similar beta-receptors and adenylate cyclase, the adenylate cyclase of hepatoma membranes was found to be less sensitive to the epinephrine-mediated activation. 3. GTP alone was found to activate adenylate cyclase of liver and hepatoma membranes to some extents when the concentration of ATP was lower (0.3 mM). When GTP was added with epinephrine, a marked, synergistic activation of adenylate cyclase was observed in liver plasma membranes, but not in hepatoma ones. 4. The synergistic activation of adenylate cyclase by epinephrine plus GTP showed a characteristic kinetic feature, reaching a maximal peak within 1 min or so after mixing. 5. Binding of [3H]epinephrine to liver membranes proceeded monophasically in the absence of GTP, while it proceeded biphasically in the presence of GTP, showing the retardation of binding at some earlier stages. GTP added at the time of binding equilibrium induced the temporary release of bound epinephrine from the beta-receptors. The GTP-induced temporary release of bound epinephrine, occurring within 4-5 min after the addition of GTP, was less marked in the hepatoma membranes as compared with the liver membranes. 6. Possible impairment of the GTP-dependent coupling mechanism in the receptor-adenylate cyclase system of hepatoma plasma membranes was suggested."}
{"id": "PMID:187241", "title": "Correlated x-ray diffraction and freeze-fracture studies on membrane model systems. Perturbations induced by freeze-fracture preparative procedures.", "content": "Lipid-water and protein-lipid-water phases have been examined by X-ray methods before and after freezing. Frozen samples have been subsequently fractured and replicated, thus permitting an evaluation of the nature of structural perturbations in samples examined by freeze-fracture electron microscopy. Important results are summarized: (1) Freezing low water content (approx. less than 25%) phases causes perturbations in the packing of hydrocarbon chains. The results suggest that freezing liquied paraffin chains produces a condensed \"glass-like\" packing. (2) Additional perturbations occur in high water content samples. After freezing, much smaller lamellar repeat distances, intense ice reflections, and extensive perturbation of fracture faces are consistant with the expulsion of water from between lamellae. Presence of glycerol generally relieves these perturbations but in some cases introduces additional lattice disorder. (3) Surprisingly, cooling by a stream of cold N2 gas (-140 degrees C) produces qualitatively the same results as rapid cooling in liquid Freon-22 (-160 degrees C). (4) Complex perturbations occur in phases containing integral membrane proteins. Interesting results have been obtained with cytochrome b5-lecithin lamellar associations which display both smooth and rough fracture faces without clearly defined particles.", "contents": "Correlated x-ray diffraction and freeze-fracture studies on membrane model systems. Perturbations induced by freeze-fracture preparative procedures. Lipid-water and protein-lipid-water phases have been examined by X-ray methods before and after freezing. Frozen samples have been subsequently fractured and replicated, thus permitting an evaluation of the nature of structural perturbations in samples examined by freeze-fracture electron microscopy. Important results are summarized: (1) Freezing low water content (approx. less than 25%) phases causes perturbations in the packing of hydrocarbon chains. The results suggest that freezing liquied paraffin chains produces a condensed \"glass-like\" packing. (2) Additional perturbations occur in high water content samples. After freezing, much smaller lamellar repeat distances, intense ice reflections, and extensive perturbation of fracture faces are consistant with the expulsion of water from between lamellae. Presence of glycerol generally relieves these perturbations but in some cases introduces additional lattice disorder. (3) Surprisingly, cooling by a stream of cold N2 gas (-140 degrees C) produces qualitatively the same results as rapid cooling in liquid Freon-22 (-160 degrees C). (4) Complex perturbations occur in phases containing integral membrane proteins. Interesting results have been obtained with cytochrome b5-lecithin lamellar associations which display both smooth and rough fracture faces without clearly defined particles."}
{"id": "PMID:187242", "title": "Glycolipids in model membranes. Spin label and freeze-etch studies.", "content": "1. Several types of glycolipid are examined in lipid bilayer model membranes as part of a program to clarify their fuction in living cells. 2. Data obtained with three spin labelled derivatives of galactosyl ceramide is reported showing a fatty acid fluidity gradient similar to that obtained with phospholipid spin labels. Some possible structural implications of the observed differences are considered. 3. Results obtained using Freeze-Etch electron microscopy and hemagglutination inhibition are given showing beef brain gangliosides in lipid vesicles to be effective receptors for influenza virus.", "contents": "Glycolipids in model membranes. Spin label and freeze-etch studies. 1. Several types of glycolipid are examined in lipid bilayer model membranes as part of a program to clarify their fuction in living cells. 2. Data obtained with three spin labelled derivatives of galactosyl ceramide is reported showing a fatty acid fluidity gradient similar to that obtained with phospholipid spin labels. Some possible structural implications of the observed differences are considered. 3. Results obtained using Freeze-Etch electron microscopy and hemagglutination inhibition are given showing beef brain gangliosides in lipid vesicles to be effective receptors for influenza virus."}
{"id": "PMID:187243", "title": "Use of phospholipid-clay complexes for determining vibrational spectra of membrane related systems.", "content": "For determining the infrared and Raman spectra of membrane related systems, a method is developed to incorporate phospholipid bilayer assemblies in a clay matrix to form ultra-thin, self-supporting films. These films, containing stabilized bilayers arranged between the silicate layers of hectorite, are in the shape of discs which measure about 2 cm in diameter and 25 microns thick and require approximately 2 mg of phospholipid for preparation. Although several spectral regions below 1100 cm-1 are masked by the host clay, both head group and acyl chain vibrations may be conveniently observed and monitored for phospholipid conformational changes.", "contents": "Use of phospholipid-clay complexes for determining vibrational spectra of membrane related systems. For determining the infrared and Raman spectra of membrane related systems, a method is developed to incorporate phospholipid bilayer assemblies in a clay matrix to form ultra-thin, self-supporting films. These films, containing stabilized bilayers arranged between the silicate layers of hectorite, are in the shape of discs which measure about 2 cm in diameter and 25 microns thick and require approximately 2 mg of phospholipid for preparation. Although several spectral regions below 1100 cm-1 are masked by the host clay, both head group and acyl chain vibrations may be conveniently observed and monitored for phospholipid conformational changes."}
{"id": "PMID:187245", "title": "Effect of the hydrophile-lipophile balance of non-ionic detergents (Triton X-series) on the solubilization of biological membranes and their integral b-type cytochromes.", "content": "The solubilization of four integral membrane proteins (i.e. cytochrome b-561 of the chromaffin granule membrane, cytochrome b5 of the endoplasmic reticulum and the mitochondrial b-type cytochrome(s) as well as cytochrome c oxidase) has been studied at 0 degrees C using the non-ionic detergents of the Triton X-series having the common hydrophobic 4(1,1,3,3-tetramethylbutyl)phenoxy (t-octyl-phenoxy) group and a variable average number (n) of polar ethylene oxide units added. Following a pre-extraction of peripheral membrane and matrix proteins with low and high salt concentration and a weak non-ionic detergent (Tween 20, average hydrophile-lipophile balance (HLB) = 16.7), the amount of heme proteins solubilized by subsequent Triton X-solutions was measured. With the detergents tested the degree of solubilization decreased in the sequence cytochrome b-561 greater than cytochrome b5 greater than mitochondrial cytochrome(s) b and parallelled the effect of the detergents on light scattering and the phospholipid to protein ratio of the three membranes. For all the b-cytochromes, the solubilizing power of the detergent increased with decreasing average length of the polar ethylene oxide chain and the hydrophile-lipophile balance as long as clouding did not occur (e.g. Triton X-114,n = 7.5 and HLB = 12.4). Thus, the greatest difference in the degree os solubilization of the three cytochromes was observed with Triton X-405 (n = 40 and HLB = 17.9). All the cytochromes were most efficiently solubilized (i.e. approx. 90%) by Triton X-100 (n = 9.5 and HLB = 13.5).", "contents": "Effect of the hydrophile-lipophile balance of non-ionic detergents (Triton X-series) on the solubilization of biological membranes and their integral b-type cytochromes. The solubilization of four integral membrane proteins (i.e. cytochrome b-561 of the chromaffin granule membrane, cytochrome b5 of the endoplasmic reticulum and the mitochondrial b-type cytochrome(s) as well as cytochrome c oxidase) has been studied at 0 degrees C using the non-ionic detergents of the Triton X-series having the common hydrophobic 4(1,1,3,3-tetramethylbutyl)phenoxy (t-octyl-phenoxy) group and a variable average number (n) of polar ethylene oxide units added. Following a pre-extraction of peripheral membrane and matrix proteins with low and high salt concentration and a weak non-ionic detergent (Tween 20, average hydrophile-lipophile balance (HLB) = 16.7), the amount of heme proteins solubilized by subsequent Triton X-solutions was measured. With the detergents tested the degree of solubilization decreased in the sequence cytochrome b-561 greater than cytochrome b5 greater than mitochondrial cytochrome(s) b and parallelled the effect of the detergents on light scattering and the phospholipid to protein ratio of the three membranes. For all the b-cytochromes, the solubilizing power of the detergent increased with decreasing average length of the polar ethylene oxide chain and the hydrophile-lipophile balance as long as clouding did not occur (e.g. Triton X-114,n = 7.5 and HLB = 12.4). Thus, the greatest difference in the degree os solubilization of the three cytochromes was observed with Triton X-405 (n = 40 and HLB = 17.9). All the cytochromes were most efficiently solubilized (i.e. approx. 90%) by Triton X-100 (n = 9.5 and HLB = 13.5)."}
{"id": "PMID:187246", "title": "Interactions of concanavalin A with chick embryo fibroblasts transformed by Rous sarcoma virus. Study with an RSV mutant thermosensitive for transformation.", "content": "The interactions between concanavalin A and chick embryo fibroblasts, normal and infected with Rous sarcoma virus (RSV-BH) or its thermosensitive mutant RSV-BH-Ta, have been studied. Normal chick embryo cells and RSV-BH transformed cells showed at 4 and 25 degrees C a similar number of concanavalin A receptors per cell. Analysis of the binding data by the Scatchard relation showed that apparent changes in binding as a function of temperature are due to the thermodynamic properties of the process and not to endocytosis. The lectin receptors on the cell surface of normal and RSV-BH infected cells showed homogeneity in their binding properties. Chick cells infected with RSV-BH-Ta showed a lectin binding behavior that was dependent on the temperature at which the cells were grown. At the permissive temperature for transformation (37 degrees C), the binding process was similar to that observed for normal and RSV-BH infected cells. At the nonpermissive temperature (41 degrees C), the cells showed at least two sets of concanavalin A receptors. The new set of receptors on the cell surface had a lower lectin affinity than those observed in the same cells at 37 degrees C. Chick cells infected with RSV-BH showed an enhanced agglutinability by concanavalin A, as compared with normal cells. Cells infected with RSV-BH-Ta showed a reversal of the correlation between increased concanavalin A agglutinability and the transformed state. At the permissive temperature for transformation, the cells were not agglutinable, whereas at the nonpermissive temperature they presented agglutinability indexes as high as those observed with RSV-BH infected cells. This enhanced agglutinability observed with cells maintained at the nonpermissive temperature for transformation may be related to the new set of low affinity receptors present at 41 degrees C.", "contents": "Interactions of concanavalin A with chick embryo fibroblasts transformed by Rous sarcoma virus. Study with an RSV mutant thermosensitive for transformation. The interactions between concanavalin A and chick embryo fibroblasts, normal and infected with Rous sarcoma virus (RSV-BH) or its thermosensitive mutant RSV-BH-Ta, have been studied. Normal chick embryo cells and RSV-BH transformed cells showed at 4 and 25 degrees C a similar number of concanavalin A receptors per cell. Analysis of the binding data by the Scatchard relation showed that apparent changes in binding as a function of temperature are due to the thermodynamic properties of the process and not to endocytosis. The lectin receptors on the cell surface of normal and RSV-BH infected cells showed homogeneity in their binding properties. Chick cells infected with RSV-BH-Ta showed a lectin binding behavior that was dependent on the temperature at which the cells were grown. At the permissive temperature for transformation (37 degrees C), the binding process was similar to that observed for normal and RSV-BH infected cells. At the nonpermissive temperature (41 degrees C), the cells showed at least two sets of concanavalin A receptors. The new set of receptors on the cell surface had a lower lectin affinity than those observed in the same cells at 37 degrees C. Chick cells infected with RSV-BH showed an enhanced agglutinability by concanavalin A, as compared with normal cells. Cells infected with RSV-BH-Ta showed a reversal of the correlation between increased concanavalin A agglutinability and the transformed state. At the permissive temperature for transformation, the cells were not agglutinable, whereas at the nonpermissive temperature they presented agglutinability indexes as high as those observed with RSV-BH infected cells. This enhanced agglutinability observed with cells maintained at the nonpermissive temperature for transformation may be related to the new set of low affinity receptors present at 41 degrees C."}
{"id": "PMID:187247", "title": "Cell growth and quabain-sensitive 86Rg+ uptake and (Na++K+)-ATPase activity in 3T3 and SV40 transformed 3T3 fibroblasts.", "content": "The uptake of ouabain-sensitive 86Rb+ uptake measured at 5 min and the uptake measured at 60 min was 4.5- and 2.7-fold greater respectively for SV40 transformed 3T3 cells compared to 3T3 cells during the late log phase of growth. This uptake, however, varied markedly with cell growth. Ouabain-sensitive 86Rb+ uptake was found to be a sensitive indicator of protein synthesis as measured by total protein content. Cessation of cell growth as measured by total protein content was associated with a decline in ouabain-sensitive 86Rb+ uptake in both cell types. This increase ouabain-sensitive cation transport was reflected in increased levels of (Na++K)-ATPase activity for SV40 3T3 cells, which showed a 2.5-fold increase V but the same Km as 3T3 cells. These results are compared with the results of related work. Possible mechanisms for these effects are discussed and how changes in cation transport might be related to alterations in cell growth.", "contents": "Cell growth and quabain-sensitive 86Rg+ uptake and (Na++K+)-ATPase activity in 3T3 and SV40 transformed 3T3 fibroblasts. The uptake of ouabain-sensitive 86Rb+ uptake measured at 5 min and the uptake measured at 60 min was 4.5- and 2.7-fold greater respectively for SV40 transformed 3T3 cells compared to 3T3 cells during the late log phase of growth. This uptake, however, varied markedly with cell growth. Ouabain-sensitive 86Rb+ uptake was found to be a sensitive indicator of protein synthesis as measured by total protein content. Cessation of cell growth as measured by total protein content was associated with a decline in ouabain-sensitive 86Rb+ uptake in both cell types. This increase ouabain-sensitive cation transport was reflected in increased levels of (Na++K)-ATPase activity for SV40 3T3 cells, which showed a 2.5-fold increase V but the same Km as 3T3 cells. These results are compared with the results of related work. Possible mechanisms for these effects are discussed and how changes in cation transport might be related to alterations in cell growth."}
{"id": "PMID:187250", "title": "In vitro synthesis of simian virus 40 DNA. I. Synthesis by a soluble extract from infected CV1 cells.", "content": "Simian Virus 40 (SV40) DNA replication was studied in vitro using cell free extracts prepared from SV40 infected CV1 cells. The cells were fractionated into a soluble cytoplasmic fraction and nuclei. The nuclei were lysed with high salt and used to prepare a soluble nuclear fraction. Both fractions displayed DNA polymerase activity as measured with activated calf thymus DNA. However, only the cytoplasmic fraction was active when SV40 DNA comonent I molecules were used as template. Under these conditions, the cytoplasmic extract was shown to catalyse the SV40 DNA dependent, in vitro incorporation of the four deoxyribonucleotides into DNA molecules which had, at both neutral and alkaline pH, the same sedimentation behavior as authentic SV40 DNA component I and component II molecules. Optimal Mg++ concentration was 5-8 mM. Incorporation of label into DNA component I molecules showed an initial lag of about 15 min., after which it was linear with time for up to 5 hrs at 32 degrees. Incorporation into DNA component II molecules proceeded without obvious lag and reached a plateau after approximately 2 hrs of incubation. It is concluded that the cytoplasmic extract supports the in vitro synthesis of SV40 DNA and that DNA component II molecules appear to be a precursor to DNA component I molecules in the reaction. Labeling of viral DNA molecules was highly dependent on ATP and on an ATP generating system. In the absence of ATP and of the energy generating system, incorporation occurred but both template and newly synthesized DNA molecules were extensively degraded.", "contents": "In vitro synthesis of simian virus 40 DNA. I. Synthesis by a soluble extract from infected CV1 cells. Simian Virus 40 (SV40) DNA replication was studied in vitro using cell free extracts prepared from SV40 infected CV1 cells. The cells were fractionated into a soluble cytoplasmic fraction and nuclei. The nuclei were lysed with high salt and used to prepare a soluble nuclear fraction. Both fractions displayed DNA polymerase activity as measured with activated calf thymus DNA. However, only the cytoplasmic fraction was active when SV40 DNA comonent I molecules were used as template. Under these conditions, the cytoplasmic extract was shown to catalyse the SV40 DNA dependent, in vitro incorporation of the four deoxyribonucleotides into DNA molecules which had, at both neutral and alkaline pH, the same sedimentation behavior as authentic SV40 DNA component I and component II molecules. Optimal Mg++ concentration was 5-8 mM. Incorporation of label into DNA component I molecules showed an initial lag of about 15 min., after which it was linear with time for up to 5 hrs at 32 degrees. Incorporation into DNA component II molecules proceeded without obvious lag and reached a plateau after approximately 2 hrs of incubation. It is concluded that the cytoplasmic extract supports the in vitro synthesis of SV40 DNA and that DNA component II molecules appear to be a precursor to DNA component I molecules in the reaction. Labeling of viral DNA molecules was highly dependent on ATP and on an ATP generating system. In the absence of ATP and of the energy generating system, incorporation occurred but both template and newly synthesized DNA molecules were extensively degraded."}
{"id": "PMID:187251", "title": "In vitro synthesis of simian virus 40 DNA. II. Evidence for a repair mechanism.", "content": "The technique of density labeling of DNA by BrdU was used to characterize the material synthesized in vitro by cytoplasmic extracts of SV40 infected cells incubated in the presence of simian virus 40 (SV40) DNA component I molecules (Girard et al, Biochimie, this volume). In a first experiment, the template was labeled beforehand in vivo using [14C]-BrdU, and the in vitro incubation was carried out in the presence of [3H]-dGTP and [3H]-dTTP. In a second experiment, the template was labeled in vivo with 32P, and the in vitro incubation was in the presence of [3H]-dGTP and BrdUTP. After digestion with the restriction endonuclease Hind II + III, the fragments from the end products of the reaction were analyzed by density gradient centrifugation, at pH 7 and pH 13. In both experiments the DNA product molecules had the same density as the resepctive DNA templates. Cellular enzymes seem to be responsible for this in vitro synthesis of DNA, since cytoplasmic extracts from uninfected cells were almost as active as those from SV40 infected cells. The system was proved efficient in the conversion of \"open circular\" molecules (component II DNA molecules) to covalently closed circular DNA molecules (relaxed component I molecules). The use of DNA complexed with histones did not impart viral specificity to the system. It is concluded that the cytoplasmic extract is only capable of supporting the repair synthesis of added viral DNA.", "contents": "In vitro synthesis of simian virus 40 DNA. II. Evidence for a repair mechanism. The technique of density labeling of DNA by BrdU was used to characterize the material synthesized in vitro by cytoplasmic extracts of SV40 infected cells incubated in the presence of simian virus 40 (SV40) DNA component I molecules (Girard et al, Biochimie, this volume). In a first experiment, the template was labeled beforehand in vivo using [14C]-BrdU, and the in vitro incubation was carried out in the presence of [3H]-dGTP and [3H]-dTTP. In a second experiment, the template was labeled in vivo with 32P, and the in vitro incubation was in the presence of [3H]-dGTP and BrdUTP. After digestion with the restriction endonuclease Hind II + III, the fragments from the end products of the reaction were analyzed by density gradient centrifugation, at pH 7 and pH 13. In both experiments the DNA product molecules had the same density as the resepctive DNA templates. Cellular enzymes seem to be responsible for this in vitro synthesis of DNA, since cytoplasmic extracts from uninfected cells were almost as active as those from SV40 infected cells. The system was proved efficient in the conversion of \"open circular\" molecules (component II DNA molecules) to covalently closed circular DNA molecules (relaxed component I molecules). The use of DNA complexed with histones did not impart viral specificity to the system. It is concluded that the cytoplasmic extract is only capable of supporting the repair synthesis of added viral DNA."}
{"id": "PMID:187253", "title": "[Phospholipid exchange between mitochondria and microsomes of rat hepatoma 27].", "content": "The phospholipid exchange in vitro between mitochondria and microsomes from rat liver and rat hepatoma 27 was investigated. On incubation with a postmicrosomal protein fraction the phospholipid exchange between subcellular fractions of the tumor was found to proceed much faster and less specific than between mitochondria and microsomes from normal liver. These results indicate that the earlier demonstrated lipid dedifferentiation of tumor cell membranes may be connected with an altered transmembrane phospholipid exchange in vivo.", "contents": "[Phospholipid exchange between mitochondria and microsomes of rat hepatoma 27]. The phospholipid exchange in vitro between mitochondria and microsomes from rat liver and rat hepatoma 27 was investigated. On incubation with a postmicrosomal protein fraction the phospholipid exchange between subcellular fractions of the tumor was found to proceed much faster and less specific than between mitochondria and microsomes from normal liver. These results indicate that the earlier demonstrated lipid dedifferentiation of tumor cell membranes may be connected with an altered transmembrane phospholipid exchange in vivo."}
{"id": "PMID:187254", "title": "[Structure of the active center of the catalytic subunit of histone kinase].", "content": "A number of unknown ATP analogues is isolated when studying the structure of the active site of catalytic histonekinase subunit. Adenosine-5'-chloromethanepyrophosphonate adenosine-5'-(beta-bromoethanepyrophosphonate) and adenosine-5'-(p-fluorosulphonylphenylphosphate) were isolated under the reaction of chloromethanephosphonic acid, beta-bromoethanephosphonic acid and n-phenolsulphofluoride respectively with AMP imidazolide. Adenosine-5'-(beta-chloroethylphosphate) was obtained from AMP morpholide and ethylenechorohydrine. Adenosine-5'-chloracetylaminomethanephosphonate and adenosine-5'-(p-fluorosulphonylbenzoylaminomethanephosphonate) were obtained in the reaction of chloroacetyc anhydride and n-fluorosulphonylbenzoylchloride. Adenosine-5'-(p-aminophenylphosphate) is synthesized under the reduction of AMP mononitrophenyl ester. The treatment of the former with chloroacetyc anhydride produced adenosine-5'-(p-chloroacetylaminophenylphosphate. Interaction of ATP analogues obtained and also of early synthesized adenosine-5'-chloromethanephosphonate and adenosine-5'-(beta-bromoethanephosphonate) with homogenous catalytic histonekinase subunit is studied. The decrease in the reaction rate of Hi histone phosphorylation is found to take place. pH optimum of the enzyme inactivation with adenosine-5'-chloromethanepyrophosphonate and adenosine-5'-(beta-chloroethylphosphate) and the protective effect of the substrate (ATP) indicate covalent blocking imidazole ring in the active site. The date obtained suggest that the functional group of the active site of catalytic histonekinase subunit is histidine imidazole ring located close to terminal ATP phosphate.", "contents": "[Structure of the active center of the catalytic subunit of histone kinase]. A number of unknown ATP analogues is isolated when studying the structure of the active site of catalytic histonekinase subunit. Adenosine-5'-chloromethanepyrophosphonate adenosine-5'-(beta-bromoethanepyrophosphonate) and adenosine-5'-(p-fluorosulphonylphenylphosphate) were isolated under the reaction of chloromethanephosphonic acid, beta-bromoethanephosphonic acid and n-phenolsulphofluoride respectively with AMP imidazolide. Adenosine-5'-(beta-chloroethylphosphate) was obtained from AMP morpholide and ethylenechorohydrine. Adenosine-5'-chloracetylaminomethanephosphonate and adenosine-5'-(p-fluorosulphonylbenzoylaminomethanephosphonate) were obtained in the reaction of chloroacetyc anhydride and n-fluorosulphonylbenzoylchloride. Adenosine-5'-(p-aminophenylphosphate) is synthesized under the reduction of AMP mononitrophenyl ester. The treatment of the former with chloroacetyc anhydride produced adenosine-5'-(p-chloroacetylaminophenylphosphate. Interaction of ATP analogues obtained and also of early synthesized adenosine-5'-chloromethanephosphonate and adenosine-5'-(beta-bromoethanephosphonate) with homogenous catalytic histonekinase subunit is studied. The decrease in the reaction rate of Hi histone phosphorylation is found to take place. pH optimum of the enzyme inactivation with adenosine-5'-chloromethanepyrophosphonate and adenosine-5'-(beta-chloroethylphosphate) and the protective effect of the substrate (ATP) indicate covalent blocking imidazole ring in the active site. The date obtained suggest that the functional group of the active site of catalytic histonekinase subunit is histidine imidazole ring located close to terminal ATP phosphate."}
{"id": "PMID:187255", "title": "[Effect of detergents and proteolytic enzymes on membrane-bound phosphohydrolases in Escherichia coli cells with repressed and depressed biosynthesis of these enzymes].", "content": "Solubilization of protein membranes by detergents and protein liberation from the membranes induced by proteolytic enzymes results in a change of activity of membrane-bound phosphohydrolases--alkaline phosphatase and polyphosphatase. The activity of enzymes under conditions of repressed and derepressed biosynthesis of phosphohydrolases changes differently, thus indicating their different membrane environment in the two types of membranes. Some data were obtained on the localization of alkaline phosphatase in a hydrophobic region, possibly in lipid bilayer and polyphosphatase in the surface layers of the membrane.", "contents": "[Effect of detergents and proteolytic enzymes on membrane-bound phosphohydrolases in Escherichia coli cells with repressed and depressed biosynthesis of these enzymes]. Solubilization of protein membranes by detergents and protein liberation from the membranes induced by proteolytic enzymes results in a change of activity of membrane-bound phosphohydrolases--alkaline phosphatase and polyphosphatase. The activity of enzymes under conditions of repressed and derepressed biosynthesis of phosphohydrolases changes differently, thus indicating their different membrane environment in the two types of membranes. Some data were obtained on the localization of alkaline phosphatase in a hydrophobic region, possibly in lipid bilayer and polyphosphatase in the surface layers of the membrane."}
{"id": "PMID:187257", "title": "Sleep analysis during drug-free weekends in chronic schizophrenic patients.", "content": "The authors made a polygraphic registration of the night sleep in a sample of 14 chronic schizophrenic patients who for several months (mean 8 months) have been on a stable, relatively low maintenance dosage of neuroleptics administered according to the drug-free weekend schedule (two consecutive drug-free days at the weekend). During this treatment none of them showed a relapse or deterioration (BPRS, CGI, and NOSIE rating scales were applied periodically). Their only complaint was of sleep deterioration during the drugfree weekend nights, especially during the second night. The polygraphic night-sleep pattern of each patient was studied during two consecutive weeks. No difference was found between the adaptation night on medication and the consecutive night on medication during the first week, and between the adaptation and readaptation nights on medication during two consecutive weeks. There was no difference in any sleep parameters between the nights on medication and the first drug-free nights. There was a signifcant difference in the total sleep time between the nights on medications and the second drug-free nights. No difference was found in any other sleep parameters in nights analysed as a blocks and in the distribution of NREM and REM stages in the first vs. the second half of the night when B3 was compared with A2. The practical implication is, that to avoid any change in nocturnal behavior it is preferable to withdraw the medication on two nonconsecutive days in the week. The evaluation of both daily and nocturnal behavior seems to be a useful tool in evaluating the first sign of the drug-withdrawal syndrome.", "contents": "Sleep analysis during drug-free weekends in chronic schizophrenic patients. The authors made a polygraphic registration of the night sleep in a sample of 14 chronic schizophrenic patients who for several months (mean 8 months) have been on a stable, relatively low maintenance dosage of neuroleptics administered according to the drug-free weekend schedule (two consecutive drug-free days at the weekend). During this treatment none of them showed a relapse or deterioration (BPRS, CGI, and NOSIE rating scales were applied periodically). Their only complaint was of sleep deterioration during the drugfree weekend nights, especially during the second night. The polygraphic night-sleep pattern of each patient was studied during two consecutive weeks. No difference was found between the adaptation night on medication and the consecutive night on medication during the first week, and between the adaptation and readaptation nights on medication during two consecutive weeks. There was no difference in any sleep parameters between the nights on medication and the first drug-free nights. There was a signifcant difference in the total sleep time between the nights on medications and the second drug-free nights. No difference was found in any other sleep parameters in nights analysed as a blocks and in the distribution of NREM and REM stages in the first vs. the second half of the night when B3 was compared with A2. The practical implication is, that to avoid any change in nocturnal behavior it is preferable to withdraw the medication on two nonconsecutive days in the week. The evaluation of both daily and nocturnal behavior seems to be a useful tool in evaluating the first sign of the drug-withdrawal syndrome."}
{"id": "PMID:187258", "title": "Probenecid-induced accumulation of cyclic nucleotides, 5-hydroxyindoleacetic acid, and homovanillic acid in cisternal spinal fluid of genetically nervous dogs.", "content": "These studies have been conducted on 40 dogs, twenty each of a genetically nervous strain and of a normal strain of short-haired pointers. The nervous strain after about age 3 months displays extreme hypervigilance, timidity, human avoidance, and often shows catatonic-like muscle rigidity when in the presence of humans or novel stimuli. Measurements of probenecid-induced accumulation of acid metabolites in cisternal cerebrospinal fluid (CSF) have been carried out. Among the compounds measured at from 1.5 hr to 6.0 hr after probenecid treatment, homovanillic acid (HVA) was similar for the two strains, 5-hydroxy-indoleacetic acid (5-HIAA) was lower, but cyclic adenosine-3',5'-monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) were higher for the nervous strain when compared with age- and sex-matched behaviorally normal dogs. Probenecid levels in CSF were similar at all points in time from 1.5 to 6.0 hr after its intravenous administration in a dose of 50 mg/kg body weight. These findings coupled with previously observed differences in the two strains suggest that hyperresponsiveness of the central nervous system (CNS) noradrenergic and cholinergic systems and a hyporesponsiveness of the serotoninergic system are related to the genetically expressed aberrant behavior.", "contents": "Probenecid-induced accumulation of cyclic nucleotides, 5-hydroxyindoleacetic acid, and homovanillic acid in cisternal spinal fluid of genetically nervous dogs. These studies have been conducted on 40 dogs, twenty each of a genetically nervous strain and of a normal strain of short-haired pointers. The nervous strain after about age 3 months displays extreme hypervigilance, timidity, human avoidance, and often shows catatonic-like muscle rigidity when in the presence of humans or novel stimuli. Measurements of probenecid-induced accumulation of acid metabolites in cisternal cerebrospinal fluid (CSF) have been carried out. Among the compounds measured at from 1.5 hr to 6.0 hr after probenecid treatment, homovanillic acid (HVA) was similar for the two strains, 5-hydroxy-indoleacetic acid (5-HIAA) was lower, but cyclic adenosine-3',5'-monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) were higher for the nervous strain when compared with age- and sex-matched behaviorally normal dogs. Probenecid levels in CSF were similar at all points in time from 1.5 to 6.0 hr after its intravenous administration in a dose of 50 mg/kg body weight. These findings coupled with previously observed differences in the two strains suggest that hyperresponsiveness of the central nervous system (CNS) noradrenergic and cholinergic systems and a hyporesponsiveness of the serotoninergic system are related to the genetically expressed aberrant behavior."}
{"id": "PMID:187259", "title": "Herpesviruses and cancer in man and subhuman primates.", "content": "Because there is strong evidence for the involvement of Epstein-Barr virus in the etiology of Burkitt's lymphoma and nasopharyngeal carcinoma, we have discussed the relationship of Epstein-Barr virus to these two diseases in the context of geographic distribution, pathology, epidemiology, genetics, immunovirology, and biochemistry. We have also discussed the relationship of Epstein-Barr virus to other diseases, both malignant and non-malignant. Although the etiologic relationship of herpes simplex virus type 2 to squamous carcinoma of the uterine cervix is not on as firm ground, we feel that some good evidence does exist. We have also discussed two oncogenic simian viruses, Herpesvirus saimiri and Herpesvirus ateles. These have a great number of similarities to EBV, and thus may provide models for the study of viral-induced oncogenesis in man. Agents similar to Epstein-Barr virus have been isolated from old world monkeys. These may possibly be of greater importance than either Herpesvirus saimiri or Herpesvirus ateles in the investigation of human virally-induced cancers.", "contents": "Herpesviruses and cancer in man and subhuman primates. Because there is strong evidence for the involvement of Epstein-Barr virus in the etiology of Burkitt's lymphoma and nasopharyngeal carcinoma, we have discussed the relationship of Epstein-Barr virus to these two diseases in the context of geographic distribution, pathology, epidemiology, genetics, immunovirology, and biochemistry. We have also discussed the relationship of Epstein-Barr virus to other diseases, both malignant and non-malignant. Although the etiologic relationship of herpes simplex virus type 2 to squamous carcinoma of the uterine cervix is not on as firm ground, we feel that some good evidence does exist. We have also discussed two oncogenic simian viruses, Herpesvirus saimiri and Herpesvirus ateles. These have a great number of similarities to EBV, and thus may provide models for the study of viral-induced oncogenesis in man. Agents similar to Epstein-Barr virus have been isolated from old world monkeys. These may possibly be of greater importance than either Herpesvirus saimiri or Herpesvirus ateles in the investigation of human virally-induced cancers."}
{"id": "PMID:187260", "title": "Mechanisms and selectivity of anthracycline aminoglycosides and other intercalating agents.", "content": "Many of the antiproliferative actions of daunorubicin and adriamycin are attributable to the results of their interaction with DNA: single and double strand breaks and inhibition of repair and of nucleic acid synthesis. Like other DNA-reactive agents, high cumulative doses produce pharmacological actions and species-specific cytotoxicities in non-proliferating myocardium and nerve cells. Evidence is reviewed suggesting that many, if not all, intercalating agents are membrane-reactive. Thus it seems likely that the selective nature of the responses by various cells and the discrete expressions of cytotoxicity may be determined by binding to specific receptors in membranes of target cells in susceptible organs and species.", "contents": "Mechanisms and selectivity of anthracycline aminoglycosides and other intercalating agents. Many of the antiproliferative actions of daunorubicin and adriamycin are attributable to the results of their interaction with DNA: single and double strand breaks and inhibition of repair and of nucleic acid synthesis. Like other DNA-reactive agents, high cumulative doses produce pharmacological actions and species-specific cytotoxicities in non-proliferating myocardium and nerve cells. Evidence is reviewed suggesting that many, if not all, intercalating agents are membrane-reactive. Thus it seems likely that the selective nature of the responses by various cells and the discrete expressions of cytotoxicity may be determined by binding to specific receptors in membranes of target cells in susceptible organs and species."}
{"id": "PMID:187261", "title": "Viral antibodies and chronic liver disease.", "content": "Serum rubella, measles and cytomegalovirus antibodies were measured in patients with various forms of chronic liver disease and compared with those in age-matched controls. In CAH all three antibodies were found in significantly greater titre than in controls,and in cryptogenic cirrhosis titres to rubella were significantly increased. In alcoholic cirrhosis none was increased. There was no correlation between antibody titres and either the presence of portal-systemic shunts or the use of steroids. In patients with CAH measles titres were significantly related to the presence of ANF and SMA.", "contents": "Viral antibodies and chronic liver disease. Serum rubella, measles and cytomegalovirus antibodies were measured in patients with various forms of chronic liver disease and compared with those in age-matched controls. In CAH all three antibodies were found in significantly greater titre than in controls,and in cryptogenic cirrhosis titres to rubella were significantly increased. In alcoholic cirrhosis none was increased. There was no correlation between antibody titres and either the presence of portal-systemic shunts or the use of steroids. In patients with CAH measles titres were significantly related to the presence of ANF and SMA."}
{"id": "PMID:187262", "title": "Anti-beta adrenoreceptor blockade activity of plasma ultrafiltrate in two uraemic patients: effect of parathyroidectomy.", "content": "A possible interaction between d-1 propranolol and hyperparathyroid plasma ultrafiltrate on guinea pig auricles has been studied in \"in vitro\" experiments. Plasma ultrafiltrates have been samples in two patients on chronci haemodialysis before (pre-PTx) and after (post-PTx) parathyroidectomy. A significant inhibition of propranolol depressant activity on cardiac contractile strength has been observed in the presence of pre-PTx plasma ultrafiltrates. On the contrary, no such inhibition was noted in the presence of post-PTx plasma ultrafiltrates.", "contents": "Anti-beta adrenoreceptor blockade activity of plasma ultrafiltrate in two uraemic patients: effect of parathyroidectomy. A possible interaction between d-1 propranolol and hyperparathyroid plasma ultrafiltrate on guinea pig auricles has been studied in \"in vitro\" experiments. Plasma ultrafiltrates have been samples in two patients on chronci haemodialysis before (pre-PTx) and after (post-PTx) parathyroidectomy. A significant inhibition of propranolol depressant activity on cardiac contractile strength has been observed in the presence of pre-PTx plasma ultrafiltrates. On the contrary, no such inhibition was noted in the presence of post-PTx plasma ultrafiltrates."}
{"id": "PMID:187263", "title": "In vitro transforming activity of EBV. I-Establishment and properties of two EBV strains (M81 and M72) produced by immortalized Callithrix jacchus lymphocytes.", "content": "In vitro transformation of Callithrix jacchus marmoset lymphocytes was achieved with a nasopharyngeal carcinoma (NPC) derived Epstein-Barr virus (EBV) strain, HKLY-28. Two permanent and virus producing lymphoblastoid cell lines, M81 and M72, were obtained. Comparison between the original HKLY-28 line and both M81 and M72 lines showed that passage in the marmosets lymphocytes greatly enhanced viral production and transforming activity of the virus as observed in cottontop derived B95.8 lymphoblastoid line.", "contents": "In vitro transforming activity of EBV. I-Establishment and properties of two EBV strains (M81 and M72) produced by immortalized Callithrix jacchus lymphocytes. In vitro transformation of Callithrix jacchus marmoset lymphocytes was achieved with a nasopharyngeal carcinoma (NPC) derived Epstein-Barr virus (EBV) strain, HKLY-28. Two permanent and virus producing lymphoblastoid cell lines, M81 and M72, were obtained. Comparison between the original HKLY-28 line and both M81 and M72 lines showed that passage in the marmosets lymphocytes greatly enhanced viral production and transforming activity of the virus as observed in cottontop derived B95.8 lymphoblastoid line."}
{"id": "PMID:187264", "title": "Phosphorylation in erythrocyte membranes from abnormally shaped cells.", "content": "Erythrocyte protein phosphorylation was examined in membrane preparations of 25 patients with hereditary spherocytosis (HS). Reduced phosphorylation in substrate polypeptides was observed in 22 HS erythrocyte membranes for both splenectomized and nonsplenectomized patients. A reduction in labeling was also observed in a polypeptide which was labeled only in the presence of cAMP. No reduction was observed in membranes from immunologically acquired spherocytosis cells or from cells from patients with hereditary elliptocytosis. Heating membranes to 45 degrees C caused negligible inhibition of membrane protein phosphorylation, while heating to 50 degrees C extensively inhibited phosphorylation. Dephosphorylation of membrane protein that occurred in isolated membranes was not dependent upon cAMP.", "contents": "Phosphorylation in erythrocyte membranes from abnormally shaped cells. Erythrocyte protein phosphorylation was examined in membrane preparations of 25 patients with hereditary spherocytosis (HS). Reduced phosphorylation in substrate polypeptides was observed in 22 HS erythrocyte membranes for both splenectomized and nonsplenectomized patients. A reduction in labeling was also observed in a polypeptide which was labeled only in the presence of cAMP. No reduction was observed in membranes from immunologically acquired spherocytosis cells or from cells from patients with hereditary elliptocytosis. Heating membranes to 45 degrees C caused negligible inhibition of membrane protein phosphorylation, while heating to 50 degrees C extensively inhibited phosphorylation. Dephosphorylation of membrane protein that occurred in isolated membranes was not dependent upon cAMP."}
{"id": "PMID:187265", "title": "Human red cells protein kinase in normal subjects and patients with hereditary spherocytosis, sickle cell disease, and autoimmune hemolytic anemia.", "content": "A somewhat simplified modification of a previously described method for the measurement of red cell membrane phosphorylation by ATP has been devised. Phosphorylation of membranes was linear with time for only 5-10 min, and linearity with membrane concentration was observed only when assays were limited to short incubation times. Protein kinase activity of hereditary spherocytosis (HS) membranes was found to be normal. However, the average phosphorylation after 60 min incubation was less in HS membranes than in normal membranes. Findings similar to those in HS membranes were observed in sickle cell disease. The Km of red cell protein kinase for ATP is approximately 10(-5) M. Membrane phosphate binding sites are not saturated in either HS or normal membranes after 1 hr incubation with ATP. Approximately 27% of phosphorylating activity is lost after 1 hr incubation at 37 degrees C. GTP is a very inefficient phosphate donor. Under the conditions of measurement employed, the enzyme is slightly stimulated by 1 muM cAMP, but is not stimulated by 1 muM cGMP. Dephosphorylation of red cell membranes after labeling occurs at a similar rate in HS as in normal membranes. Although a mild abnormally in membrane phosphorylation is observed in HS, this could not be demonstrated to be due to a decrease in protein kinase activity or in alterations of its kinetic properties. The abnormally seen is not specific for HS.", "contents": "Human red cells protein kinase in normal subjects and patients with hereditary spherocytosis, sickle cell disease, and autoimmune hemolytic anemia. A somewhat simplified modification of a previously described method for the measurement of red cell membrane phosphorylation by ATP has been devised. Phosphorylation of membranes was linear with time for only 5-10 min, and linearity with membrane concentration was observed only when assays were limited to short incubation times. Protein kinase activity of hereditary spherocytosis (HS) membranes was found to be normal. However, the average phosphorylation after 60 min incubation was less in HS membranes than in normal membranes. Findings similar to those in HS membranes were observed in sickle cell disease. The Km of red cell protein kinase for ATP is approximately 10(-5) M. Membrane phosphate binding sites are not saturated in either HS or normal membranes after 1 hr incubation with ATP. Approximately 27% of phosphorylating activity is lost after 1 hr incubation at 37 degrees C. GTP is a very inefficient phosphate donor. Under the conditions of measurement employed, the enzyme is slightly stimulated by 1 muM cAMP, but is not stimulated by 1 muM cGMP. Dephosphorylation of red cell membranes after labeling occurs at a similar rate in HS as in normal membranes. Although a mild abnormally in membrane phosphorylation is observed in HS, this could not be demonstrated to be due to a decrease in protein kinase activity or in alterations of its kinetic properties. The abnormally seen is not specific for HS."}
{"id": "PMID:187266", "title": "Improvement of Chediak-Higashi leukocyte function by cyclic guanosine monophosphate.", "content": "The addition of cholinergic agents and cyclic 3'5'-guanosine monophosphate (cGMP) to polymorphonuclear leukocytes in vitro from a patient with Chediak-Higashi syndrome corrected the impaired release of the lysosomal enzyme, beta-glucuronidase, to normal. Coinciding with the improvement in degranulation, the bactericidal capacity was enhanced to normal. Similar concentrations of cholinergic agents potentiated chemotaxis to control values. On the other hand, the phagocytic rate of lipopolysaccharide-coated paraffin-oil droplets was not altered by the cholinergic agents. The improvement in Chediak-Higashi syndrome polymorphonuclear leukocyte function by the addition of cholinergic agents and dibutyryl cGMP suggested disturbed intracellular cyclic nucleotide levels.", "contents": "Improvement of Chediak-Higashi leukocyte function by cyclic guanosine monophosphate. The addition of cholinergic agents and cyclic 3'5'-guanosine monophosphate (cGMP) to polymorphonuclear leukocytes in vitro from a patient with Chediak-Higashi syndrome corrected the impaired release of the lysosomal enzyme, beta-glucuronidase, to normal. Coinciding with the improvement in degranulation, the bactericidal capacity was enhanced to normal. Similar concentrations of cholinergic agents potentiated chemotaxis to control values. On the other hand, the phagocytic rate of lipopolysaccharide-coated paraffin-oil droplets was not altered by the cholinergic agents. The improvement in Chediak-Higashi syndrome polymorphonuclear leukocyte function by the addition of cholinergic agents and dibutyryl cGMP suggested disturbed intracellular cyclic nucleotide levels."}
{"id": "PMID:187267", "title": "[Extra-articular cervical synovial sarcomas. Review of the literature apropos of 2 cases].", "content": "Two cases of extra-articular synovial sarcoma are reported together with a review of the literature. The analysis of 44 cases shows that this tumor appears among young people particularly between 10 and 30 years of age and is twice more frequent among males. There can be metastasis mostly in lungs (11 times), which can sometimes appear much later (more than 10 years after the first diagnosis). The 5-year survival rate is here, 13/18; this is higher than for similar tumors located in the juxta-articular area. The great size of the tumoral nodule (more than 5 centimeters) is of a bad omen for the prognosis. As regards therapy, isolated surgical exeresis seems to have given results at least as good as these of surgery associated to radiotherapy. In all cases, the diagnosis is based on a light microscopic study which shows two tightly linked histological patterns: a proliferation of fusiform cells and glandular like formations. This feature is not definitely pathognostic and is very similar to tumors of glandular origin, with myoepithelial proliferation. Some examples could indeed be classified as extra-articular cervical synovialo-sarcoma. They could originate in pharyngeal and laryngeal mucous glands. This histogenetic hypothesis could account for the highly favorable evolution of some cases which were reported as synovialo-sarcoma.", "contents": "[Extra-articular cervical synovial sarcomas. Review of the literature apropos of 2 cases]. Two cases of extra-articular synovial sarcoma are reported together with a review of the literature. The analysis of 44 cases shows that this tumor appears among young people particularly between 10 and 30 years of age and is twice more frequent among males. There can be metastasis mostly in lungs (11 times), which can sometimes appear much later (more than 10 years after the first diagnosis). The 5-year survival rate is here, 13/18; this is higher than for similar tumors located in the juxta-articular area. The great size of the tumoral nodule (more than 5 centimeters) is of a bad omen for the prognosis. As regards therapy, isolated surgical exeresis seems to have given results at least as good as these of surgery associated to radiotherapy. In all cases, the diagnosis is based on a light microscopic study which shows two tightly linked histological patterns: a proliferation of fusiform cells and glandular like formations. This feature is not definitely pathognostic and is very similar to tumors of glandular origin, with myoepithelial proliferation. Some examples could indeed be classified as extra-articular cervical synovialo-sarcoma. They could originate in pharyngeal and laryngeal mucous glands. This histogenetic hypothesis could account for the highly favorable evolution of some cases which were reported as synovialo-sarcoma."}
{"id": "PMID:187268", "title": "Thymidine kinase gene transfer by herpes simplex virus.", "content": "The current state of knowledge concerning the biochemical transformation by Herpes Simplex virus (HSV) of mammalian cells lacking the enzyme thymidine kinase (TK) is reviewed. Transformation of thymidine kinase negative mouse cells (LTK-) to the TK+ phenotype by ultraviolet light-inactivated HSV preparations depends both on the irradiation dose and on the multiplicity of infection. Once stably associated with the transformed cell, the HSV thymidine kinase appears to be regulated differently than the cellular enzyme: HSV TK activity is maximal in stationary cells, whereas cellular TK activity is maximal during the S-pphase of growing cells. Furthermore, infection with an HSV TK- mutant virus leads to the induction of TK activity in HSV TK+ cells, but not in normal TK+ cells. Recent studies indicate that in addition to the TK gene, at least one other HSV gene, perhaps a structural antigen of the virion, is also transferred to TK- cells. This is consistent with the finding that a clone of HSV TK+ cells harbors approximately five copies per cell of 23 per cent of the HSV genome.", "contents": "Thymidine kinase gene transfer by herpes simplex virus. The current state of knowledge concerning the biochemical transformation by Herpes Simplex virus (HSV) of mammalian cells lacking the enzyme thymidine kinase (TK) is reviewed. Transformation of thymidine kinase negative mouse cells (LTK-) to the TK+ phenotype by ultraviolet light-inactivated HSV preparations depends both on the irradiation dose and on the multiplicity of infection. Once stably associated with the transformed cell, the HSV thymidine kinase appears to be regulated differently than the cellular enzyme: HSV TK activity is maximal in stationary cells, whereas cellular TK activity is maximal during the S-pphase of growing cells. Furthermore, infection with an HSV TK- mutant virus leads to the induction of TK activity in HSV TK+ cells, but not in normal TK+ cells. Recent studies indicate that in addition to the TK gene, at least one other HSV gene, perhaps a structural antigen of the virion, is also transferred to TK- cells. This is consistent with the finding that a clone of HSV TK+ cells harbors approximately five copies per cell of 23 per cent of the HSV genome."}
{"id": "PMID:187269", "title": "The biology and serology of Epstein-Barr virus (EBV) infections.", "content": "The Epstein-Barr virus (EBV), carried by the majority of the world's adult human population, is closely associated with three known human diseases; infectious mononucleosis IM), Burkitts lymphoma (BL) and nasopharyngeal carcinoma (NPC). It is now generally accepted that EBV plays an active role in the etiology of BL and NPC rather than simply being a \"passenger\". Considerable evidence also argues for the participation of \"co-factors\" in these two diseases. Environmental co-factors appear needed to explain the peculiar geographical distribution of BL. Among various possibilities that must be considered are insect-transmitted agents that could lead to eventual immunosuppression and/or stimulate further proliferation of EBV-transformed cells, thereby permitting an additional cytogenetic evolution towards malignancy. Recent studies have uncovered a possible cytogenetic co-factor in the ethiology of BL; the 8-14 chromosomal translocation. Genetic co-factors, on the other hand, are likely to be involved in the etiology of NCP. EBV is a B-cell associated virus. Carrier lymphoid cell lines obtained either by in vitro \"immortalization\" of human cord-blood lymphocytes or by explants from IM and African BL donors harbor multiple copies of the EBV genome, and viral genetic sequences have also been directly detected in biopsies of African BL. The state of the viral genomes in the carrier cell appears to be such that some are integrated into the cellular DNA while others exist as free, covalently closed circular molecules.", "contents": "The biology and serology of Epstein-Barr virus (EBV) infections. The Epstein-Barr virus (EBV), carried by the majority of the world's adult human population, is closely associated with three known human diseases; infectious mononucleosis IM), Burkitts lymphoma (BL) and nasopharyngeal carcinoma (NPC). It is now generally accepted that EBV plays an active role in the etiology of BL and NPC rather than simply being a \"passenger\". Considerable evidence also argues for the participation of \"co-factors\" in these two diseases. Environmental co-factors appear needed to explain the peculiar geographical distribution of BL. Among various possibilities that must be considered are insect-transmitted agents that could lead to eventual immunosuppression and/or stimulate further proliferation of EBV-transformed cells, thereby permitting an additional cytogenetic evolution towards malignancy. Recent studies have uncovered a possible cytogenetic co-factor in the ethiology of BL; the 8-14 chromosomal translocation. Genetic co-factors, on the other hand, are likely to be involved in the etiology of NCP. EBV is a B-cell associated virus. Carrier lymphoid cell lines obtained either by in vitro \"immortalization\" of human cord-blood lymphocytes or by explants from IM and African BL donors harbor multiple copies of the EBV genome, and viral genetic sequences have also been directly detected in biopsies of African BL. The state of the viral genomes in the carrier cell appears to be such that some are integrated into the cellular DNA while others exist as free, covalently closed circular molecules."}
{"id": "PMID:187273", "title": "Influenza: its antigenic variation and ecology.", "content": "Influenza viruses have two surface antigens, the glycoprotein structures hemagglutinin (HA) and neuraminidase (NA). Antibodies to each of these are associated with immunity, but the structures themselves are antigenically variable. When an antigenic change is gradual over time it is referred to as a drift, while a sudden complete or major change in either or both antigens is termed a shift. The mechanism of antigenic drift is usually attributed to selection of preexisting mutants by pressure from increasing immunity in the human population. The mechanism of antigenic shift is less clear, but one tentative hypothesis is that shifts arise from mammalian or avian reservoirs, or through genetic recombination of human and animal influenza strains.", "contents": "Influenza: its antigenic variation and ecology. Influenza viruses have two surface antigens, the glycoprotein structures hemagglutinin (HA) and neuraminidase (NA). Antibodies to each of these are associated with immunity, but the structures themselves are antigenically variable. When an antigenic change is gradual over time it is referred to as a drift, while a sudden complete or major change in either or both antigens is termed a shift. The mechanism of antigenic drift is usually attributed to selection of preexisting mutants by pressure from increasing immunity in the human population. The mechanism of antigenic shift is less clear, but one tentative hypothesis is that shifts arise from mammalian or avian reservoirs, or through genetic recombination of human and animal influenza strains."}
{"id": "PMID:187274", "title": "A perfusion culture system for virus vaccine manufacture in diploid cell cultures.", "content": "Development of a new perfusion culture system for the production of attenuated poliomyelitis virus in cultures of diploid cells is described. The growth characteristics of the diploid cells (MRC-5) were found to be normal in the perfused system. Procedures for the routine production of cell cultures at twice the cell density of stationary bottle cultures were established. The yield of virus (Lsc 2ab) per cell and per unit of surface growth area were observed to be significantly higher in the perfused system than in parallel stationary bottle culture controls--by factors of three- and five-fold, respectively. The field was confirmed to be within the experimental range when small production-scale vessels were used. Subject to satisfactory results in the testing of the virus product, this system could be highly economic in large-scale vaccine manufacture.", "contents": "A perfusion culture system for virus vaccine manufacture in diploid cell cultures. Development of a new perfusion culture system for the production of attenuated poliomyelitis virus in cultures of diploid cells is described. The growth characteristics of the diploid cells (MRC-5) were found to be normal in the perfused system. Procedures for the routine production of cell cultures at twice the cell density of stationary bottle cultures were established. The yield of virus (Lsc 2ab) per cell and per unit of surface growth area were observed to be significantly higher in the perfused system than in parallel stationary bottle culture controls--by factors of three- and five-fold, respectively. The field was confirmed to be within the experimental range when small production-scale vessels were used. Subject to satisfactory results in the testing of the virus product, this system could be highly economic in large-scale vaccine manufacture."}
{"id": "PMID:187272", "title": "[Cutaneous herpesvirus infections and malignant blood disorders. Epidemiology].", "content": "One hundred and ten skin infections with herpes virus were seen in a uniform group of 1,002 lymphoma-leukaemias dominated by non-Hodgkin's lymphoma (385) and Hodgkin's Disease (327). They appeared with a significantly increased frequency in the course of Hodgkin's Disease, and between the ages of 60 and 69 for the other groups. In the Hodgkin's cases they appeared characteristically during complete remission and in the others during the active phase of their disease. Only exceptionally was there evidence of contact infection. Also these infections seemed mainly due to the re-awakening of a latent virus infection as against a failure of natural defense mechanisms of the organism, which the disease itself and the therapeutic regime might alter in a variable fashion.", "contents": "[Cutaneous herpesvirus infections and malignant blood disorders. Epidemiology]. One hundred and ten skin infections with herpes virus were seen in a uniform group of 1,002 lymphoma-leukaemias dominated by non-Hodgkin's lymphoma (385) and Hodgkin's Disease (327). They appeared with a significantly increased frequency in the course of Hodgkin's Disease, and between the ages of 60 and 69 for the other groups. In the Hodgkin's cases they appeared characteristically during complete remission and in the others during the active phase of their disease. Only exceptionally was there evidence of contact infection. Also these infections seemed mainly due to the re-awakening of a latent virus infection as against a failure of natural defense mechanisms of the organism, which the disease itself and the therapeutic regime might alter in a variable fashion."}
{"id": "PMID:187276", "title": "The effect of dibutyryl cyclic adenosine-3'-5'-monophosphate on protein secretion from the rat exocrine pancreas in vitro.", "content": "1 The mechanism by which dibutyryl cyclic adenosine-3'-5'-monophosphate (dibutyryl cyclic AMP) potentiates the secretory effect of carbachol in rat exocrine pancreas was investigated. 2 Dibutyryl cyclic AMP potentiated the secretory effect of carbachol only at carbachol concentrations greater than or equal to 10(-7) mol/l; was independent of carbachol at concentrations greater than 10(-7) mol/l and was inversely proportional to extracellular [Ca2+]. 3 Carbachol increased and dibutyryl cyclic AMP reduced the rate of 45Ca efflux from the tissue. 4 A-23187 stimulated 3H-protein release in the presence of Ca2+ and this effect was potentiated by dibutyryl cyclic AMP; the degree of potentiation was inversely proportional to extracellular [Ca2+]. At 10(-3) mol/l [Ca2+] the potentiation occurred only at ionophore concentrations less than or equal to 10(-6) mol/litre. 5 These results support the hypothesis that dibutyryl cyclic AMP potentiates the effect of secretagogues in rat exocrine pancreas by maintaining an elevated intracellular calcium concentration. It does so by inhibiting Ca2+ efflux. The results also suggest that the limiting factor in carbachol-stimulated secretion, at all concentrations of carbachol, is intracellular [Ca2+].", "contents": "The effect of dibutyryl cyclic adenosine-3'-5'-monophosphate on protein secretion from the rat exocrine pancreas in vitro. 1 The mechanism by which dibutyryl cyclic adenosine-3'-5'-monophosphate (dibutyryl cyclic AMP) potentiates the secretory effect of carbachol in rat exocrine pancreas was investigated. 2 Dibutyryl cyclic AMP potentiated the secretory effect of carbachol only at carbachol concentrations greater than or equal to 10(-7) mol/l; was independent of carbachol at concentrations greater than 10(-7) mol/l and was inversely proportional to extracellular [Ca2+]. 3 Carbachol increased and dibutyryl cyclic AMP reduced the rate of 45Ca efflux from the tissue. 4 A-23187 stimulated 3H-protein release in the presence of Ca2+ and this effect was potentiated by dibutyryl cyclic AMP; the degree of potentiation was inversely proportional to extracellular [Ca2+]. At 10(-3) mol/l [Ca2+] the potentiation occurred only at ionophore concentrations less than or equal to 10(-6) mol/litre. 5 These results support the hypothesis that dibutyryl cyclic AMP potentiates the effect of secretagogues in rat exocrine pancreas by maintaining an elevated intracellular calcium concentration. It does so by inhibiting Ca2+ efflux. The results also suggest that the limiting factor in carbachol-stimulated secretion, at all concentrations of carbachol, is intracellular [Ca2+]."}
{"id": "PMID:187270", "title": "Latent infection of mouse cells with human cytomegalovirus.", "content": "Infection of secondary mouse fibroblast cultures with human cytomegalovirus (HCMV) led to the production of viral antigens in the absence of detectable virus replication. Antigen production was not dependent on viral DNA synthesis since it was not inhibited by cytosine arabinoside. Beginning at 15 days post-infection, viral-specific antigens were no longer observable in infected cultures, but could be induced by iododeoxyuridine (IUDR) treatment. Such cultures carry HCMV genetic information in a latent, unexpressed, state. Fusion of latently-infected mouse cells with human fibroblasts also induced viral-specific antigens, but no detectable virus replication, in the resulting heterokaryons. However, upon IUDR treatment of heterokaryons, or of the mouse cells prior to fusion, antigens characteristic of the late stages of virus replication appeared, and infectious CMV could be detected. Thus, it appears that the non-permissive (mouse) cell genome is dominant, and continues to regulate viral gene expression in heterokaryons formed with permissive (human) cells.", "contents": "Latent infection of mouse cells with human cytomegalovirus. Infection of secondary mouse fibroblast cultures with human cytomegalovirus (HCMV) led to the production of viral antigens in the absence of detectable virus replication. Antigen production was not dependent on viral DNA synthesis since it was not inhibited by cytosine arabinoside. Beginning at 15 days post-infection, viral-specific antigens were no longer observable in infected cultures, but could be induced by iododeoxyuridine (IUDR) treatment. Such cultures carry HCMV genetic information in a latent, unexpressed, state. Fusion of latently-infected mouse cells with human fibroblasts also induced viral-specific antigens, but no detectable virus replication, in the resulting heterokaryons. However, upon IUDR treatment of heterokaryons, or of the mouse cells prior to fusion, antigens characteristic of the late stages of virus replication appeared, and infectious CMV could be detected. Thus, it appears that the non-permissive (mouse) cell genome is dominant, and continues to regulate viral gene expression in heterokaryons formed with permissive (human) cells."}
{"id": "PMID:187271", "title": "[Epidemiology and nature of the association between herpesviruses (EBV and herpes simplex) and several human tumors. Recent results].", "content": "The association between EBV and two human tumours (BL and NPC) is presented. The BL prospective study conducted by the International Agency for Research on Cancer is progressing well, and up to date 10 pre-BL sera have been available and tested. The results show that not only every serum has VCA antibodies 7 to 31 months prior to tumour development, but that the VCA titres of such pre-BL sera appear higher than that of various age-sex matched controls. These preliminary results would favour a chronic and heavy EBV infection as a risk factor for BL. The role of co-factors, such as malaria, is discussed together with proposals of anti-malaria partial suppression scheme. The association between HSV-2 and cervical carcinoma is weaker, and HSV-2 infection could become an epidemiological marker, rather than an etiological agent for the tumour.", "contents": "[Epidemiology and nature of the association between herpesviruses (EBV and herpes simplex) and several human tumors. Recent results]. The association between EBV and two human tumours (BL and NPC) is presented. The BL prospective study conducted by the International Agency for Research on Cancer is progressing well, and up to date 10 pre-BL sera have been available and tested. The results show that not only every serum has VCA antibodies 7 to 31 months prior to tumour development, but that the VCA titres of such pre-BL sera appear higher than that of various age-sex matched controls. These preliminary results would favour a chronic and heavy EBV infection as a risk factor for BL. The role of co-factors, such as malaria, is discussed together with proposals of anti-malaria partial suppression scheme. The association between HSV-2 and cervical carcinoma is weaker, and HSV-2 infection could become an epidemiological marker, rather than an etiological agent for the tumour."}
{"id": "PMID:187281", "title": "Two-dimensional analysis of the redox state of the rat cerebral cortex in vivo by NADH fluorescence photography.", "content": "A photographic method for measuring two-dimensional changes in NADH fluorescence and hemoglobin distributions in the rat cerebral cortex in vivo has been developed. Intracellular NADH was excited by UV light peaking at 360 nm and the emission was observed through a window with the maximum transmission at 450 nm. The fluorescence photographs (360 leads to 450 nm) required 20-25 sec exposures at the aperture opening of f/5.6 and the reflectance photographs (360 leads to 360 nm) 10 sec exposures at f/32. The digitization of photographic images was achieved either by a PDP-8-controlled microdensitometer coupled to an A/D converter or by a combination of a manually operated microdensitometer and a computer-controlled digitizer. In the latter case, a photographic negative was scanned with a Joyce-Loebl microdensitometer in parallel lines 170 mum apart, and the densitometric tracings were digitized with a PDP-8-controlled TV digitizer. The digital data were processed by DEC PDP-10 computer and the results were displayed in 3-dimensional surfaces. Nitrogen anoxia caused increases in fluorescence at 450 nm ranging from 10 to 75% fo the normoxic fluorescence intensities (after correcting for the logarithmic characteristics of the photographic films) and decreases in reflectance intensities in the range of 10-30%. The spatial resolution of the present technique is limited to approximately 30 mum X 30 mum on the cortical surface and the time resolution to 10-25 sec. The optical properties of the cerebral cortex in vivo appear to be controlled primarily by blood vessel patterns and hemodynamic factors and secondarily by the redox state of the tissue. Evidence for a heterogeneous redox response of the cerebral cortex toward N2 anoxia was obtained.", "contents": "Two-dimensional analysis of the redox state of the rat cerebral cortex in vivo by NADH fluorescence photography. A photographic method for measuring two-dimensional changes in NADH fluorescence and hemoglobin distributions in the rat cerebral cortex in vivo has been developed. Intracellular NADH was excited by UV light peaking at 360 nm and the emission was observed through a window with the maximum transmission at 450 nm. The fluorescence photographs (360 leads to 450 nm) required 20-25 sec exposures at the aperture opening of f/5.6 and the reflectance photographs (360 leads to 360 nm) 10 sec exposures at f/32. The digitization of photographic images was achieved either by a PDP-8-controlled microdensitometer coupled to an A/D converter or by a combination of a manually operated microdensitometer and a computer-controlled digitizer. In the latter case, a photographic negative was scanned with a Joyce-Loebl microdensitometer in parallel lines 170 mum apart, and the densitometric tracings were digitized with a PDP-8-controlled TV digitizer. The digital data were processed by DEC PDP-10 computer and the results were displayed in 3-dimensional surfaces. Nitrogen anoxia caused increases in fluorescence at 450 nm ranging from 10 to 75% fo the normoxic fluorescence intensities (after correcting for the logarithmic characteristics of the photographic films) and decreases in reflectance intensities in the range of 10-30%. The spatial resolution of the present technique is limited to approximately 30 mum X 30 mum on the cortical surface and the time resolution to 10-25 sec. The optical properties of the cerebral cortex in vivo appear to be controlled primarily by blood vessel patterns and hemodynamic factors and secondarily by the redox state of the tissue. Evidence for a heterogeneous redox response of the cerebral cortex toward N2 anoxia was obtained."}
{"id": "PMID:187284", "title": "[Ultramicroscopic observations on glomic tumors].", "content": "Ultra microscopic study of three glomic tumours established the presence in these of myoepithelial cells with a cytoplasma rich in fibrils and deprived of secretory granules. These typical cells are very different of these of chimioreceptors of chromophile system.", "contents": "[Ultramicroscopic observations on glomic tumors]. Ultra microscopic study of three glomic tumours established the presence in these of myoepithelial cells with a cytoplasma rich in fibrils and deprived of secretory granules. These typical cells are very different of these of chimioreceptors of chromophile system."}
{"id": "PMID:187285", "title": "[Effect on paradoxal sleep of experimental limbic epilepsy induced by intraseptal injection of ouabain].", "content": "Limbic epilepsy secondary to intraseptal injection of ouabain induces a suppresion of paradoxical sleep, for a duration of 10 to 30 hours, followed by progressive recuperation of paradoxical sleep without any rebound phenomenon. A reappearance of a normal electrical activity is necessary for a rapid restoration of paradoxical sleep. When septal or hippocamp-geniculate spikes persist the recovery is slower and smaller.", "contents": "[Effect on paradoxal sleep of experimental limbic epilepsy induced by intraseptal injection of ouabain]. Limbic epilepsy secondary to intraseptal injection of ouabain induces a suppresion of paradoxical sleep, for a duration of 10 to 30 hours, followed by progressive recuperation of paradoxical sleep without any rebound phenomenon. A reappearance of a normal electrical activity is necessary for a rapid restoration of paradoxical sleep. When septal or hippocamp-geniculate spikes persist the recovery is slower and smaller."}
{"id": "PMID:187286", "title": "Histomorphometric determination of formation rates of archaeological bone.", "content": "Archaeological rib samples were subjected to quantitative histologic analysis to determine rates of cortical bone formation. Histologic features are usually well enough preserved to permit the determination of mean annual Haversian bone formation rate averaged over the life span of the individual. Moreover, gross estimates of aging archaeological bone correlate well with histologic parameters expected for particular ages. Age-associated changes in bone histomorphology in extinct populations have remained essentially unchanged for at least 1,600 years. Bone formation rates determined for these populations agree with age-matched values determined for extant Homo sapiens. A relatively high frequency of pathologic conditions reported by others for the Ledders population may be reflected by the wide range of histomorphometric parameters present in the ribs of these individuals. On the basis of morphophysiologic relationships in extant populations, it can be assumed that mean annual osteonal creation frequency, and mean annual Haversian bone formation rate can be reliably determined in extinct populations. To our knowledge, this is the first time a dynamic physiologic parameter has been measured in an extinct population of H. sapiens.", "contents": "Histomorphometric determination of formation rates of archaeological bone. Archaeological rib samples were subjected to quantitative histologic analysis to determine rates of cortical bone formation. Histologic features are usually well enough preserved to permit the determination of mean annual Haversian bone formation rate averaged over the life span of the individual. Moreover, gross estimates of aging archaeological bone correlate well with histologic parameters expected for particular ages. Age-associated changes in bone histomorphology in extinct populations have remained essentially unchanged for at least 1,600 years. Bone formation rates determined for these populations agree with age-matched values determined for extant Homo sapiens. A relatively high frequency of pathologic conditions reported by others for the Ledders population may be reflected by the wide range of histomorphometric parameters present in the ribs of these individuals. On the basis of morphophysiologic relationships in extant populations, it can be assumed that mean annual osteonal creation frequency, and mean annual Haversian bone formation rate can be reliably determined in extinct populations. To our knowledge, this is the first time a dynamic physiologic parameter has been measured in an extinct population of H. sapiens."}
{"id": "PMID:187287", "title": "Responses of fetal rat bone cells and bone organ cultures to the ionophore, A23187.", "content": "The ionophore A23187 produced a rapid transient increase in the rate of calcium uptake by isolated fetal rat bone cells. There was no effect on calcium efflux or total cellular calcium. The magnitude of the effect on influx was amplified when the cell were incubated at 4 degrees C. Cellular metabolic functions and resorption of cultured fetal rat bones (release of 45Ca from pre-labeled long bone) were affected by A23187 in a biphasic manner: cell cyclic AMP (cAMP) was increased by 0.1 and 0.3 mug/ml of the ionophore, whereas 10 mug/ml was either ineffective or lowered the cAMP levels. The high A23187 concentration abolished the stimulatory effects of parathyroid hormone and methylisobutylxanthine. Concentrations of 0.1 and 0.3 mug/ml A23187 stimulated bone resorption. The effect was abolished by calcitonin. Ionophore concentrations above 1 mug/ml produced less bone resorption. These higher concentrations antagonized the bone-resorbing effect of parathyroid hormone and 1,25-dihydroxyvitamin D3. A23187 at 5 and 10 mug/ml decreased bone cell lactate and ATP. Thus at low concentrations, A23187 produced effects on bone similar to those of parathyroid hormone, suggesting that calcium is the primary initiator of PTH-induced bone resorption. At the higher concentrations A23187 may have a general inhibitory effect on cell metabolism.", "contents": "Responses of fetal rat bone cells and bone organ cultures to the ionophore, A23187. The ionophore A23187 produced a rapid transient increase in the rate of calcium uptake by isolated fetal rat bone cells. There was no effect on calcium efflux or total cellular calcium. The magnitude of the effect on influx was amplified when the cell were incubated at 4 degrees C. Cellular metabolic functions and resorption of cultured fetal rat bones (release of 45Ca from pre-labeled long bone) were affected by A23187 in a biphasic manner: cell cyclic AMP (cAMP) was increased by 0.1 and 0.3 mug/ml of the ionophore, whereas 10 mug/ml was either ineffective or lowered the cAMP levels. The high A23187 concentration abolished the stimulatory effects of parathyroid hormone and methylisobutylxanthine. Concentrations of 0.1 and 0.3 mug/ml A23187 stimulated bone resorption. The effect was abolished by calcitonin. Ionophore concentrations above 1 mug/ml produced less bone resorption. These higher concentrations antagonized the bone-resorbing effect of parathyroid hormone and 1,25-dihydroxyvitamin D3. A23187 at 5 and 10 mug/ml decreased bone cell lactate and ATP. Thus at low concentrations, A23187 produced effects on bone similar to those of parathyroid hormone, suggesting that calcium is the primary initiator of PTH-induced bone resorption. At the higher concentrations A23187 may have a general inhibitory effect on cell metabolism."}
{"id": "PMID:187288", "title": "Inhibition of apatite formation by phosphorylated metabolites and macromolecules.", "content": "Apatite formation from synthetic extracellular fluids is rate-limited both at the initial amorphous precursor deposition step and at the amorphous-crystalline transformation reaction. Nucleotide diphosphates and triphosphates and low molecular weight metabolites containing two attached ester phosphate groups all inhibited amorphous-crystalline conversion at concentrations of 10(-5) to 10(-6)M. Both native and synthetic polynucleotides as well as the phosphoproteins from rat dentin or egg yolk also inhibited crystal formation from amorphous calcium phosphate. In all cases, substantial amounts of inhibitor molecules were incorporated into the stabilized amorphous precipitates. Treatment of isolated, inhibitor-stabilized amorphous precipitates with hydrolytic enzymes such as alkaline phosphatase or papain reversed the inhibitory effect and permitted crystallization to proceed normally.", "contents": "Inhibition of apatite formation by phosphorylated metabolites and macromolecules. Apatite formation from synthetic extracellular fluids is rate-limited both at the initial amorphous precursor deposition step and at the amorphous-crystalline transformation reaction. Nucleotide diphosphates and triphosphates and low molecular weight metabolites containing two attached ester phosphate groups all inhibited amorphous-crystalline conversion at concentrations of 10(-5) to 10(-6)M. Both native and synthetic polynucleotides as well as the phosphoproteins from rat dentin or egg yolk also inhibited crystal formation from amorphous calcium phosphate. In all cases, substantial amounts of inhibitor molecules were incorporated into the stabilized amorphous precipitates. Treatment of isolated, inhibitor-stabilized amorphous precipitates with hydrolytic enzymes such as alkaline phosphatase or papain reversed the inhibitory effect and permitted crystallization to proceed normally."}
{"id": "PMID:187289", "title": "The effect of p,p'-dichlorodiphenyltrichloroethane on levels of guanosine 3',5'-cyclic monophosphate and adenosine 3',5'-cyclic monophosphate in two species of insects.", "content": "Within 1 h after topical application of a convulsive dose (4 mug per fly, 47 mg/kg) of p,p'-dichlorodiphenyltrichloroethane (DDT) to the adult male of Sarcophaga bullata Parker, guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels rose by 71.5% (P less than 0.05) in the head, 159.5% (P less than 0.01) in the thorax, and 23.4% (P greater than 0.05) in the abdomen compared to controls. Adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels were not significantly affected by the DDT treatment. A convulsive dose (100 mug per larva, 250 mg/kg) of DDT applied to larvae of Mamestra configurata Wlk. caused the whole body level of cyclic GMP to rise by 81.6% (P less than 0.01) after 1 h, and by 95.9% (P less than 0.01) after 3 h. Levels of cyclic AMP were not affected. A hypothesis is advanced suggesting that an abnormally high rate of discharge of acetylcholine (and in the later stages of poisoning, its actual accumulation) at central cholinergic synapses causes cyclic GMP levels to rise, perhaps in post-synaptic cells. The elevated cyclic GMP-cyclic AMP ratio found in DDT-poisoned insects may be of fundamental importance in the complex sequence of events leading to tremor, hyperexcitability, paralysis, and death.", "contents": "The effect of p,p'-dichlorodiphenyltrichloroethane on levels of guanosine 3',5'-cyclic monophosphate and adenosine 3',5'-cyclic monophosphate in two species of insects. Within 1 h after topical application of a convulsive dose (4 mug per fly, 47 mg/kg) of p,p'-dichlorodiphenyltrichloroethane (DDT) to the adult male of Sarcophaga bullata Parker, guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels rose by 71.5% (P less than 0.05) in the head, 159.5% (P less than 0.01) in the thorax, and 23.4% (P greater than 0.05) in the abdomen compared to controls. Adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels were not significantly affected by the DDT treatment. A convulsive dose (100 mug per larva, 250 mg/kg) of DDT applied to larvae of Mamestra configurata Wlk. caused the whole body level of cyclic GMP to rise by 81.6% (P less than 0.01) after 1 h, and by 95.9% (P less than 0.01) after 3 h. Levels of cyclic AMP were not affected. A hypothesis is advanced suggesting that an abnormally high rate of discharge of acetylcholine (and in the later stages of poisoning, its actual accumulation) at central cholinergic synapses causes cyclic GMP levels to rise, perhaps in post-synaptic cells. The elevated cyclic GMP-cyclic AMP ratio found in DDT-poisoned insects may be of fundamental importance in the complex sequence of events leading to tremor, hyperexcitability, paralysis, and death."}
{"id": "PMID:187290", "title": "The function of mitochondrial genes in Neurospora crassa.", "content": "The 18 extranuclear mutants of Neurospora crassa, without exception, have abnormal mitochondrial respiratory systems. On the basis of genetic, phenotypic and physiological criteria, these mutants are divided into four groups: 1) the cytochrome aa3 and b deficient \"poky\" variants that are defective in mitochondrial ribosomes assembly, 2) the cytochrome aa3 deficient mutants, [mi-3] and [exn-5], that appear to have genetic lesions affecting a component of a regulatory system controlling cytochrome aa3 synthesis, 3) the cytochrome aa3 and b deficient \"stopper\" mutants with physiological lesions that probably affect mitochondrial protein synthesis, and 4) cni-3, a mutant that is constitutive for an inducible mitochondrial cyanide-insensitive oxidase in spite of having a normal cytochrome mediated electron-transport system. It is proposed that the mitochondrial genophore not only codes for cellular components that are essential for the formation of the mitochondrial protein synthesizing apparatus, but also for components of a regulatory system that coordinates the expression of nuclear and mitochondrial genes during the biogenesis of the mitochondrial electorn-transport system.", "contents": "The function of mitochondrial genes in Neurospora crassa. The 18 extranuclear mutants of Neurospora crassa, without exception, have abnormal mitochondrial respiratory systems. On the basis of genetic, phenotypic and physiological criteria, these mutants are divided into four groups: 1) the cytochrome aa3 and b deficient \"poky\" variants that are defective in mitochondrial ribosomes assembly, 2) the cytochrome aa3 deficient mutants, [mi-3] and [exn-5], that appear to have genetic lesions affecting a component of a regulatory system controlling cytochrome aa3 synthesis, 3) the cytochrome aa3 and b deficient \"stopper\" mutants with physiological lesions that probably affect mitochondrial protein synthesis, and 4) cni-3, a mutant that is constitutive for an inducible mitochondrial cyanide-insensitive oxidase in spite of having a normal cytochrome mediated electron-transport system. It is proposed that the mitochondrial genophore not only codes for cellular components that are essential for the formation of the mitochondrial protein synthesizing apparatus, but also for components of a regulatory system that coordinates the expression of nuclear and mitochondrial genes during the biogenesis of the mitochondrial electorn-transport system."}
{"id": "PMID:187291", "title": "Necrotic enteritis in broiler chickens. III. Reproduction of the disease.", "content": "Lesions typical of necrotic enteritis could be produced experimentally in from 11-26% of broiler chickens consuming feed containing approximately 10(7) Clostridium perfringens per gram. Highest mortality was produced using isolates from field cases of necrotic enteritis which were reisolated from experimental cases in the laboratory. Penicillin in the drinking water at 100,000 I.U./litre completely prevented mortality whereas chloramphenicol at 110 mg/litre delayed the onset and reduced the number of deaths compared to controls.", "contents": "Necrotic enteritis in broiler chickens. III. Reproduction of the disease. Lesions typical of necrotic enteritis could be produced experimentally in from 11-26% of broiler chickens consuming feed containing approximately 10(7) Clostridium perfringens per gram. Highest mortality was produced using isolates from field cases of necrotic enteritis which were reisolated from experimental cases in the laboratory. Penicillin in the drinking water at 100,000 I.U./litre completely prevented mortality whereas chloramphenicol at 110 mg/litre delayed the onset and reduced the number of deaths compared to controls."}
{"id": "PMID:187292", "title": "A foot-and-mouth disease vaccine for swine.", "content": "An inactivated vaccine containing purified foot-and-mouth disease virus type O1, strain Brugge, emulsified with incomplete Freund's adjuvant was studied in swine. The antigen mass ranged from 0.02 to 416 mug in 0.25 ml of vaccine. At 90 days postinoculation (DPI) 33 to 100% of the swine which had been inoculated with 0.72% mug or larger amounts of antigen were protected against challenge. There was little protection at 182 DPI although the neutralizing titers obtained with 2.9, 34.6 and 416 mug doses of antigen were similar to those observed at 90 DPI. The 50% protective dose for swine was approximately 2.3 mug of antigen whether used in a freshly prepared state or after storage at 4 degrees C for 105 or 259 days. Significant protection was afforded when small volumes (0.1 and 0.5 ml) of vaccine were applied with a jet injector gun to the ear or neck of swine. Initial tissue reactions at the site of inoculation were minimal with these small doses of vaccine and generally disappeared ny 90 DPI.", "contents": "A foot-and-mouth disease vaccine for swine. An inactivated vaccine containing purified foot-and-mouth disease virus type O1, strain Brugge, emulsified with incomplete Freund's adjuvant was studied in swine. The antigen mass ranged from 0.02 to 416 mug in 0.25 ml of vaccine. At 90 days postinoculation (DPI) 33 to 100% of the swine which had been inoculated with 0.72% mug or larger amounts of antigen were protected against challenge. There was little protection at 182 DPI although the neutralizing titers obtained with 2.9, 34.6 and 416 mug doses of antigen were similar to those observed at 90 DPI. The 50% protective dose for swine was approximately 2.3 mug of antigen whether used in a freshly prepared state or after storage at 4 degrees C for 105 or 259 days. Significant protection was afforded when small volumes (0.1 and 0.5 ml) of vaccine were applied with a jet injector gun to the ear or neck of swine. Initial tissue reactions at the site of inoculation were minimal with these small doses of vaccine and generally disappeared ny 90 DPI."}
{"id": "PMID:187293", "title": "Isolation of a subgroup two adenovirus from calf with weak calf syndrome.", "content": "A viral agent, designated Id-1, was isolated from the buffy coat of a calf suffering from weak calf syndrome. The virus replicated on bovine salivary gland cells and caused cytopathic effect within four days after infection-Cytopathic effect was characterized by rounding and clumping of cells. Stained preparations of infected monolayers revealed multiple intranuclear inclusions. The agent was found to be resistant to chloroform, ether, trypsin, sodium desoxycholate, oxytetracycline and a pH range of three to nine. The virus was sensitive to 5-iodo-2'-deoxyuridine and to a temperature of 70 degrees C. Cross neutralization tests with Id-1 antiserum and bovine adenovirus type 7 (strain Fujuroi) antiserum resulted in complete neutralilation of both viruses with four or less antibody units of homologous or heterologous antiserum.", "contents": "Isolation of a subgroup two adenovirus from calf with weak calf syndrome. A viral agent, designated Id-1, was isolated from the buffy coat of a calf suffering from weak calf syndrome. The virus replicated on bovine salivary gland cells and caused cytopathic effect within four days after infection-Cytopathic effect was characterized by rounding and clumping of cells. Stained preparations of infected monolayers revealed multiple intranuclear inclusions. The agent was found to be resistant to chloroform, ether, trypsin, sodium desoxycholate, oxytetracycline and a pH range of three to nine. The virus was sensitive to 5-iodo-2'-deoxyuridine and to a temperature of 70 degrees C. Cross neutralization tests with Id-1 antiserum and bovine adenovirus type 7 (strain Fujuroi) antiserum resulted in complete neutralilation of both viruses with four or less antibody units of homologous or heterologous antiserum."}
{"id": "PMID:187294", "title": "Immunization of broiler chickens with a commercial infectious laryngotracheitis vaccine in the drinking water.", "content": "Seventy-five thousand broiler chickens in four flocks were immunized at four weeks of age with a commercial infectious laryngotracheitis vaccine administered in the drinking water. Three of the flocks exhibited a vaccine reaction represented by mild respiratory illness between seven and 14 days after vaccination. Immunity challenge experiments demonstrated 97% protection in one trial and 67% in another trial in which the dose of challenge virus was increased fourfold. In the latter trial a parallel comparative vaccination by eye administration was 87% protective. None of the vaccinated birds died of the challenge exposure whereas all the unvaccinated control chickens became ill, several showed the acute severe form of the disease and 36% died. Similar favourable results were obtained in large-scale water immunization programs involving more than 200,000 birds. Serum antibody levels determined before immunity challenge were, within wide limits, inversely related to the severity of clinical disease which developed from the challenge inoculation.", "contents": "Immunization of broiler chickens with a commercial infectious laryngotracheitis vaccine in the drinking water. Seventy-five thousand broiler chickens in four flocks were immunized at four weeks of age with a commercial infectious laryngotracheitis vaccine administered in the drinking water. Three of the flocks exhibited a vaccine reaction represented by mild respiratory illness between seven and 14 days after vaccination. Immunity challenge experiments demonstrated 97% protection in one trial and 67% in another trial in which the dose of challenge virus was increased fourfold. In the latter trial a parallel comparative vaccination by eye administration was 87% protective. None of the vaccinated birds died of the challenge exposure whereas all the unvaccinated control chickens became ill, several showed the acute severe form of the disease and 36% died. Similar favourable results were obtained in large-scale water immunization programs involving more than 200,000 birds. Serum antibody levels determined before immunity challenge were, within wide limits, inversely related to the severity of clinical disease which developed from the challenge inoculation."}
{"id": "PMID:187295", "title": "The detection of transmissible gastroenteritis viral antibodies by immunodiffusion.", "content": "Precipitating antibodies against transmissible gastroenteritis viral antigens were detected by the immunodiffusion test in two transmissible gastroenteritis viral hyperimmune antisera and in antiserum prepared against haemagglutinating encephalomyelitis virus but not in sera from several species of normal animals, in antisera prepared against a variety of othet viruses and bacteria or sera from swine with bacterial enteritis. When the immunodiffusion test was compared with the virus neutralization test for the detection of transmissible gastroeneritis viral antibodies in 20 swine sera certain samples which contained high titres of virus neutralizing antibodies failed to produce precipitation while other sera were positive in the immunodiffusion test although their virus neutralizing antibody titres were relatively low. Precipitating antibodies were also detected by immunodiffusion in several samples of milk whey from a sow which had been vaccinated with inactivated transmissible gastroenteritis virus.", "contents": "The detection of transmissible gastroenteritis viral antibodies by immunodiffusion. Precipitating antibodies against transmissible gastroenteritis viral antigens were detected by the immunodiffusion test in two transmissible gastroenteritis viral hyperimmune antisera and in antiserum prepared against haemagglutinating encephalomyelitis virus but not in sera from several species of normal animals, in antisera prepared against a variety of othet viruses and bacteria or sera from swine with bacterial enteritis. When the immunodiffusion test was compared with the virus neutralization test for the detection of transmissible gastroeneritis viral antibodies in 20 swine sera certain samples which contained high titres of virus neutralizing antibodies failed to produce precipitation while other sera were positive in the immunodiffusion test although their virus neutralizing antibody titres were relatively low. Precipitating antibodies were also detected by immunodiffusion in several samples of milk whey from a sow which had been vaccinated with inactivated transmissible gastroenteritis virus."}
{"id": "PMID:187296", "title": "Transmissible gastroenteritis virus: plaques and a plaque neutralization test.", "content": "A plaquing system and plaque neutralization test in porcine thyroid cells were used to study different transmissible gastroenteritis isolates and hemagglutinating encephalomyelitis virus. Among transmissible gastroenteritis virus isolates, plaque size varied considerably and mixed size ranges sometimes occurred. The most recently isolated viruses produced smaller plaques than the laboratory viruses or hemagglutinating encephalomyelitis virus. All transmissible gastroenteritis virus isolates reacted in the plaque neutralization test with a transmissible gastroenteritis virus antiserum which showed no activity against hemagglutinating encephalomyelitis virus. Plaque neutralization results both from experimentally infected pigs and following a field outbreak demonstrated the reliability of this test and its greater sensitivity than the conventional tube test.", "contents": "Transmissible gastroenteritis virus: plaques and a plaque neutralization test. A plaquing system and plaque neutralization test in porcine thyroid cells were used to study different transmissible gastroenteritis isolates and hemagglutinating encephalomyelitis virus. Among transmissible gastroenteritis virus isolates, plaque size varied considerably and mixed size ranges sometimes occurred. The most recently isolated viruses produced smaller plaques than the laboratory viruses or hemagglutinating encephalomyelitis virus. All transmissible gastroenteritis virus isolates reacted in the plaque neutralization test with a transmissible gastroenteritis virus antiserum which showed no activity against hemagglutinating encephalomyelitis virus. Plaque neutralization results both from experimentally infected pigs and following a field outbreak demonstrated the reliability of this test and its greater sensitivity than the conventional tube test."}
{"id": "PMID:187297", "title": "Antibody response in pigs inoculated with transmissible gastroenteritis virus and cross reactions among ten isolates.", "content": "Groups of two or three day old pigs were inoculated intravenously with cell culture grown transmissible gastroenteritis virus. A single or a multiple dosage schedule was used. The magnitude of immune response was measured in terms of serum neutralization indices. A single dose of relatively attenuated virus caused mild clinical signs of transmissible gastroenteritis infection in the pigs and induced a low level of antibody in the serum by the seventh day after inoculation. Repeated injections of virus at seven day intervals stimulated little increase in antibody titers. However, high serum antibody titers were obtained for all pigs if the time interval between injections was extended to 15 days. Sera obtained early after exposure to live transmissible gastroenteritis virus contained mainly IgM antibody whereas sera obtained later after exposure contained mainly IgG antibody. Ten plaque purified isolates of transmissible gastroenteritis virus, comprising eight American isolates, one Japanese isolate and one British isolate were indistinguishable by means of reciprocal plaque reduction neutralization tests.", "contents": "Antibody response in pigs inoculated with transmissible gastroenteritis virus and cross reactions among ten isolates. Groups of two or three day old pigs were inoculated intravenously with cell culture grown transmissible gastroenteritis virus. A single or a multiple dosage schedule was used. The magnitude of immune response was measured in terms of serum neutralization indices. A single dose of relatively attenuated virus caused mild clinical signs of transmissible gastroenteritis infection in the pigs and induced a low level of antibody in the serum by the seventh day after inoculation. Repeated injections of virus at seven day intervals stimulated little increase in antibody titers. However, high serum antibody titers were obtained for all pigs if the time interval between injections was extended to 15 days. Sera obtained early after exposure to live transmissible gastroenteritis virus contained mainly IgM antibody whereas sera obtained later after exposure contained mainly IgG antibody. Ten plaque purified isolates of transmissible gastroenteritis virus, comprising eight American isolates, one Japanese isolate and one British isolate were indistinguishable by means of reciprocal plaque reduction neutralization tests."}
{"id": "PMID:187298", "title": "Transfer of parental immunity to infectious laryngotracheitis in chicks.", "content": "The transfer of parental immunity to infectious laryngotracheitis was appraised by measuring serum antibody levels in 150 chicks from the day of hatch up to five weeks. The breeder flock which had received primary vaccination at eight weeks and a booster at 20 weeks transferred high antibody levels which fell markedly within two weeks and remained constant thereafter. Chicks whose parents were vaccinated at 20 weeks only, had low antibody levels throughout. These low levels, in either group of chicks, appeared to offer marginal protection only and were unlikely to inhibit the response to primary vaccination.", "contents": "Transfer of parental immunity to infectious laryngotracheitis in chicks. The transfer of parental immunity to infectious laryngotracheitis was appraised by measuring serum antibody levels in 150 chicks from the day of hatch up to five weeks. The breeder flock which had received primary vaccination at eight weeks and a booster at 20 weeks transferred high antibody levels which fell markedly within two weeks and remained constant thereafter. Chicks whose parents were vaccinated at 20 weeks only, had low antibody levels throughout. These low levels, in either group of chicks, appeared to offer marginal protection only and were unlikely to inhibit the response to primary vaccination."}
{"id": "PMID:187299", "title": "The isolation and characterization of a strain of infectious bovine rhinotracheitis virus from stillbirth in swine.", "content": "A virus, designated 5089, which was isolated from tissue samples from two stillborn pig fetuses was identified on the basis of its morphology, cytopathology, physiocochemical and serological characteristics as a strain of infectious bovine rhinotracheitis (IBR) virus. Three piglets inoculated intranasally with 5089 virus did not respond serologically and no virus was isolated from their tissues at intervals after inoculation. They showed neither clinical signs nor significant lesions. A colostrum deprived calf which was inoculated intranasally with the same virus developed clinical signs typical of the respiratory form of IBR and the virus was reisolated on several occasions from nasal swabs.", "contents": "The isolation and characterization of a strain of infectious bovine rhinotracheitis virus from stillbirth in swine. A virus, designated 5089, which was isolated from tissue samples from two stillborn pig fetuses was identified on the basis of its morphology, cytopathology, physiocochemical and serological characteristics as a strain of infectious bovine rhinotracheitis (IBR) virus. Three piglets inoculated intranasally with 5089 virus did not respond serologically and no virus was isolated from their tissues at intervals after inoculation. They showed neither clinical signs nor significant lesions. A colostrum deprived calf which was inoculated intranasally with the same virus developed clinical signs typical of the respiratory form of IBR and the virus was reisolated on several occasions from nasal swabs."}
{"id": "PMID:187300", "title": "Observations on recovery mechanisms from feline viral rhinotracheitis.", "content": "Experiments were designed to determine immunological mechanisms responsible for controlling dissemination of feline rhinotracheitis virus in feline cell cultures. Virus infected cells could be destroyed by three mechanisms--antibody and complement mediated lysis, direct lymphocyte cytotoxicity and antibody dependent cell-mediated cytotoxicity. This latter immune parameter was mediated by both lymphocytes and macrophages and varied in extent in different cats. To ascertain the potential importance of the immunological parameters in curtailing viral spread, the time when virus infected cells could be destroyed by each component was related to the chronological events of viral replication and dissemination. Intracellular infectious virus and intracellular spread occurred at six to seven hours postinfection and extracellular spread at nine to ten hours postinfection. Antibody complement lysis and antibody dependent cell-mediated cytotoxicity occurred at six hours postinfection and direct cytotoxicity at eight hours postinfection. The relevance that these findings might have in relation to the occurrence and frequency of recrudescent disease is discussed.", "contents": "Observations on recovery mechanisms from feline viral rhinotracheitis. Experiments were designed to determine immunological mechanisms responsible for controlling dissemination of feline rhinotracheitis virus in feline cell cultures. Virus infected cells could be destroyed by three mechanisms--antibody and complement mediated lysis, direct lymphocyte cytotoxicity and antibody dependent cell-mediated cytotoxicity. This latter immune parameter was mediated by both lymphocytes and macrophages and varied in extent in different cats. To ascertain the potential importance of the immunological parameters in curtailing viral spread, the time when virus infected cells could be destroyed by each component was related to the chronological events of viral replication and dissemination. Intracellular infectious virus and intracellular spread occurred at six to seven hours postinfection and extracellular spread at nine to ten hours postinfection. Antibody complement lysis and antibody dependent cell-mediated cytotoxicity occurred at six hours postinfection and direct cytotoxicity at eight hours postinfection. The relevance that these findings might have in relation to the occurrence and frequency of recrudescent disease is discussed."}
{"id": "PMID:187301", "title": "A comparison of some serological tests for bluetongue virus infection.", "content": "The plaque neutralization, complement fixation, and agar gel precipitin tests were compared by measuring bluetongue virus antibody in 137 serums from experimental animals (cattle and sheep) and suspected field reactors (cattle and deer). In general, the tests agreed well with each other. Plaque neutralization titers began earlier than the other two and went much higher than the complement fixation titers. Plaque neutralization titers usually peaked between two and three weeks after exposure and complement fixation titers from four to six weeks. The greater sensitivity of the plaque neutralization test allowed the detection of all complement fixation and agar gel precipitin reactors whereas occasionally the latter two tests failed to detect plaque neutralization reactors.", "contents": "A comparison of some serological tests for bluetongue virus infection. The plaque neutralization, complement fixation, and agar gel precipitin tests were compared by measuring bluetongue virus antibody in 137 serums from experimental animals (cattle and sheep) and suspected field reactors (cattle and deer). In general, the tests agreed well with each other. Plaque neutralization titers began earlier than the other two and went much higher than the complement fixation titers. Plaque neutralization titers usually peaked between two and three weeks after exposure and complement fixation titers from four to six weeks. The greater sensitivity of the plaque neutralization test allowed the detection of all complement fixation and agar gel precipitin reactors whereas occasionally the latter two tests failed to detect plaque neutralization reactors."}
{"id": "PMID:187302", "title": "Bovine leukosis. V. Epidemiological study of bovine C-type virus by the use of the complement fixation test.", "content": "Persistent levels of serum antibodies to bovine C-type virus were demonstrated by the complement fixation test in cattle of a leukosis herd during an observation period of one and one half years. Using the same method, no antibodies were detected in a control herd.", "contents": "Bovine leukosis. V. Epidemiological study of bovine C-type virus by the use of the complement fixation test. Persistent levels of serum antibodies to bovine C-type virus were demonstrated by the complement fixation test in cattle of a leukosis herd during an observation period of one and one half years. Using the same method, no antibodies were detected in a control herd."}
{"id": "PMID:187303", "title": "Mechanism of protection from primary bovine viral diarrhea virus infection. I. The effects of dexamethasone.", "content": "A series of investigations was designed to study the role of cellular immunity and passive antibody in protecting neonatal calves from primary bovine viral diarrhea virus infection. Administration of corticosteroids (dexamethasone) in doses capable of suppressing cellular immunity markedly potentiated systemic bovine viral diarrhea virus infection in calves which lacked bovine viral diarrhea passive neutralizing antibody. Immunosuppressed calves did not form neutralizing antibody to bovine viral diarrhea virus and developed a fatal viremia. Calves with high levels of passive bovine viral diarrhea neutralizing antibodies were protected from the effect of corticosteroids. The results suggest an essential role for humoral passive antibody, but not for cellular immunity, in protection from primary systemic bovine viral diarrhea virus infection in calves.", "contents": "Mechanism of protection from primary bovine viral diarrhea virus infection. I. The effects of dexamethasone. A series of investigations was designed to study the role of cellular immunity and passive antibody in protecting neonatal calves from primary bovine viral diarrhea virus infection. Administration of corticosteroids (dexamethasone) in doses capable of suppressing cellular immunity markedly potentiated systemic bovine viral diarrhea virus infection in calves which lacked bovine viral diarrhea passive neutralizing antibody. Immunosuppressed calves did not form neutralizing antibody to bovine viral diarrhea virus and developed a fatal viremia. Calves with high levels of passive bovine viral diarrhea neutralizing antibodies were protected from the effect of corticosteroids. The results suggest an essential role for humoral passive antibody, but not for cellular immunity, in protection from primary systemic bovine viral diarrhea virus infection in calves."}
{"id": "PMID:187304", "title": "Neutralizing activity in the gastrointestinal contents of piglets vaccinated with a live or formaldehyde-inactivated porcine enterovirus.", "content": "Neutralizing activity against porcine enterovirus strain T80 was demonstrated in the gastrointestinal contents of piglets given live T80 virus orally or parenterally, but little or no neutralizing activity was detected in the gastrointestinal contents of piglets given formaldehyde-inactivated virus by either route. The gastrointestinal neutralizing response was first detected 14 days after oral dosing, coincidentally with a fall in the titre and distribution of virus. The neutralizing response was highest at 23 days, and dropped markedly by 36 days, whereas no response was detected until 36 days in piglets which received live virus by the intramuscular route. Virus generally appeared earlier, was more widely distributed, and reached higher titres in the gastrointestinal tract of piglets which received live virus orally than in those which received the same preparation by the intramuscular route. The highest serum neutralizing response occurred in the piglets given live virus orally. The serum response in the piglets which received live virus intramuscularly appeared earlier and was biphasic. The serum response in the piglets receiving formaldehyde-inactivated virus appeared as early as the response to live virus given by the same route, but remained relatively low throughout the period of observation.", "contents": "Neutralizing activity in the gastrointestinal contents of piglets vaccinated with a live or formaldehyde-inactivated porcine enterovirus. Neutralizing activity against porcine enterovirus strain T80 was demonstrated in the gastrointestinal contents of piglets given live T80 virus orally or parenterally, but little or no neutralizing activity was detected in the gastrointestinal contents of piglets given formaldehyde-inactivated virus by either route. The gastrointestinal neutralizing response was first detected 14 days after oral dosing, coincidentally with a fall in the titre and distribution of virus. The neutralizing response was highest at 23 days, and dropped markedly by 36 days, whereas no response was detected until 36 days in piglets which received live virus by the intramuscular route. Virus generally appeared earlier, was more widely distributed, and reached higher titres in the gastrointestinal tract of piglets which received live virus orally than in those which received the same preparation by the intramuscular route. The highest serum neutralizing response occurred in the piglets given live virus orally. The serum response in the piglets which received live virus intramuscularly appeared earlier and was biphasic. The serum response in the piglets receiving formaldehyde-inactivated virus appeared as early as the response to live virus given by the same route, but remained relatively low throughout the period of observation."}
{"id": "PMID:187305", "title": "The pulmonary clearance of Pasteurella hemolytica in calves infected with bovine parainfluenza-3 virus.", "content": "The purpose of this study was to determine if parainfluenza-3 virus in calves interfered with normal pulmonary bacterial clearance. Three groups (A, B and C) of four calves each were exposed to an aerosol of parainfluenza-3 virus. Three days later the four hour pulmonary clearance of Pasteurella hemolytica was determined on the first group (A), seven days later on the second (B) and 11 days later on the third (C). Group A had a mean pulmonary bacterial retention of 3.6 +/- 3.5%. Group B was 83.1 +/- 35.9% and Group C was 41.2 +/- 30.9%. The results demonstrate that parainfluenza-3 virus interfered with the pulmonary bacterial clearance of Pasteurella hemolytica particularly on day 7 and also on day 11 but not on day 3. This inhibition of pulmonary clearance caused by the virus may be a key factor in the pathogenesis of pneumonic pasteurellosis. Histological examination of the lungs did not demonstrate a correlation between pulmonary retention of bacteria and the development of pathological changes.", "contents": "The pulmonary clearance of Pasteurella hemolytica in calves infected with bovine parainfluenza-3 virus. The purpose of this study was to determine if parainfluenza-3 virus in calves interfered with normal pulmonary bacterial clearance. Three groups (A, B and C) of four calves each were exposed to an aerosol of parainfluenza-3 virus. Three days later the four hour pulmonary clearance of Pasteurella hemolytica was determined on the first group (A), seven days later on the second (B) and 11 days later on the third (C). Group A had a mean pulmonary bacterial retention of 3.6 +/- 3.5%. Group B was 83.1 +/- 35.9% and Group C was 41.2 +/- 30.9%. The results demonstrate that parainfluenza-3 virus interfered with the pulmonary bacterial clearance of Pasteurella hemolytica particularly on day 7 and also on day 11 but not on day 3. This inhibition of pulmonary clearance caused by the virus may be a key factor in the pathogenesis of pneumonic pasteurellosis. Histological examination of the lungs did not demonstrate a correlation between pulmonary retention of bacteria and the development of pathological changes."}
{"id": "PMID:187306", "title": "Effects of endotoxin on carbohydrate metabolism in inbred mice.", "content": "Effects of endotoxin on carbohydrate metabolism were studied in A/HeJ (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) inbred mice. A/HeJ mice developed hypoglycemia within two hours after endotoxin injection, yet liver glycogen content did not differ from controls. Similarly treated C3H/HeJ mice did not develop significant hypoglycemia. Administration of glucagon to endotoxin-treated A/HeJ mice failed to elevate their blood glucose concentrations, while endotoxin-treated mice of the same strain did respond to dibutyryl cyclic AMP with a significant elevation of blood glucose. C3H/HeJ mice on the other hand responded to glucagon and dibutyryl cyclic AMP with elevated blood glucose. Endotoxin-treated C3H/HeJ but not A/HeJ mice were able to carry out gluconeogenesis induced by prednisolone, while both inbred strains showed active glycogenesis after administration of an exogenous glucose load. Administration of glucagon resulted in diminished liver glycogen concentrations in A/HeJ endotoxin-treated mice suggesting no impairment of glycogenolysis. The inability of endotoxin-treated A/HeJ mice to respond to glucagon could be due to impairment of gluconeogenesis. Although endotoxin interfered with the capacity of both inbred strains to respond to glucagon administration with elevation of liver cyclic AMP, the effect was significantly more severe in A/HeJ mice. The susceptibility of A/HeJ mice to the lethal effect of endotoxin may be related to the apparent sensitivity of carbohydrate metabolic pathways to disturbance by endotoxin.", "contents": "Effects of endotoxin on carbohydrate metabolism in inbred mice. Effects of endotoxin on carbohydrate metabolism were studied in A/HeJ (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) inbred mice. A/HeJ mice developed hypoglycemia within two hours after endotoxin injection, yet liver glycogen content did not differ from controls. Similarly treated C3H/HeJ mice did not develop significant hypoglycemia. Administration of glucagon to endotoxin-treated A/HeJ mice failed to elevate their blood glucose concentrations, while endotoxin-treated mice of the same strain did respond to dibutyryl cyclic AMP with a significant elevation of blood glucose. C3H/HeJ mice on the other hand responded to glucagon and dibutyryl cyclic AMP with elevated blood glucose. Endotoxin-treated C3H/HeJ but not A/HeJ mice were able to carry out gluconeogenesis induced by prednisolone, while both inbred strains showed active glycogenesis after administration of an exogenous glucose load. Administration of glucagon resulted in diminished liver glycogen concentrations in A/HeJ endotoxin-treated mice suggesting no impairment of glycogenolysis. The inability of endotoxin-treated A/HeJ mice to respond to glucagon could be due to impairment of gluconeogenesis. Although endotoxin interfered with the capacity of both inbred strains to respond to glucagon administration with elevation of liver cyclic AMP, the effect was significantly more severe in A/HeJ mice. The susceptibility of A/HeJ mice to the lethal effect of endotoxin may be related to the apparent sensitivity of carbohydrate metabolic pathways to disturbance by endotoxin."}
{"id": "PMID:187307", "title": "The possible local synthesis of antibodies to herpes simplex virus in normal cerebrospinal fluid.", "content": "We have used the technique of antibody mediated cell dependent immune lysis to examine paired samples of serum and CSF for antibody to herpes simplex virus. The 40 patients studied had no inflammatory disease of the nervous system, yet 20 of the CSF specimens did have antiviral antibody. This is an extremely sensitive technique for the detection of at least one type of antiviral antibody and \"in vitro\" is a very effective way of killing virus infected cells. There is no correlation between the level of antiviral antibody in the CSF with the total protein content, but the high CSF: serum antibody ratio in some subjects who are particularly susceptible to recurrent herpes infection raises the possibility that local stimulation and production of this antibody may occur.", "contents": "The possible local synthesis of antibodies to herpes simplex virus in normal cerebrospinal fluid. We have used the technique of antibody mediated cell dependent immune lysis to examine paired samples of serum and CSF for antibody to herpes simplex virus. The 40 patients studied had no inflammatory disease of the nervous system, yet 20 of the CSF specimens did have antiviral antibody. This is an extremely sensitive technique for the detection of at least one type of antiviral antibody and \"in vitro\" is a very effective way of killing virus infected cells. There is no correlation between the level of antiviral antibody in the CSF with the total protein content, but the high CSF: serum antibody ratio in some subjects who are particularly susceptible to recurrent herpes infection raises the possibility that local stimulation and production of this antibody may occur."}
{"id": "PMID:187308", "title": "A theory of the mechanism of cerebral vasospasm and its reversal, the role of calcium and cyclic AMP.", "content": "It is proposed that the basic mechanism of vasospasm which sometimes follows subarachnoid hemorrhage is dependent on increased free intracellular calcium ion produced by spasmogens from closely applied extravasated blood. Relaxation of this spasm occurs when the intracellular cyclic AMP levels are raised, resulting in sequestration of calcium ion by the vascular smooth muscle cell sarcoplasmic reticulum.", "contents": "A theory of the mechanism of cerebral vasospasm and its reversal, the role of calcium and cyclic AMP. It is proposed that the basic mechanism of vasospasm which sometimes follows subarachnoid hemorrhage is dependent on increased free intracellular calcium ion produced by spasmogens from closely applied extravasated blood. Relaxation of this spasm occurs when the intracellular cyclic AMP levels are raised, resulting in sequestration of calcium ion by the vascular smooth muscle cell sarcoplasmic reticulum."}
{"id": "PMID:187309", "title": "Pathology of the heart in Friedreich's ataxia: review of the literature and report of one case.", "content": "A single case of typical Friedreich's ataxia was analyzed for cardiac changes and compared to the findings from the literature. Macroscopically, there was a cardiomegaly with some degree of ventricular hypertrophy and probable mild dilatation of the auricles. The more important and constant histologic changes were myocardial fibrosis and degeneration of the cardiac muscle cells. Granular deposits of calcium salts and iron were found in the muscle cells. A cardiomyopathy hypertrophic in type and occasionally obstructive appears to be an integral part of Friedreich's ataxia.", "contents": "Pathology of the heart in Friedreich's ataxia: review of the literature and report of one case. A single case of typical Friedreich's ataxia was analyzed for cardiac changes and compared to the findings from the literature. Macroscopically, there was a cardiomegaly with some degree of ventricular hypertrophy and probable mild dilatation of the auricles. The more important and constant histologic changes were myocardial fibrosis and degeneration of the cardiac muscle cells. Granular deposits of calcium salts and iron were found in the muscle cells. A cardiomyopathy hypertrophic in type and occasionally obstructive appears to be an integral part of Friedreich's ataxia."}
{"id": "PMID:187310", "title": "Cytotoxic lymphocytes in infectious mononucleosis.", "content": "Seven patients with a clinical diagnosis of infectious mononucleosis (IM) and detectable heterophil antibodies were found to have peripheral blood lymphocytes that were cytotoxic for lymphoid cells containing Epstein-Barr virus from a patient with Burkitt's lymphoma. The cytotoxic lymphocytes persisted in the peripheral circulation for up to 45 days. Patients who had had IM 1 to 5 years previously lacked such cytotoxic lymphocytes. Patients who had signs and symptoms of IM but no detectable heterophil antibodies lacked cytotoxic lymphocytes. The lymphocytes of one patient with IM showed progressive diminution of cytotoxic ability after prednisone treatment.", "contents": "Cytotoxic lymphocytes in infectious mononucleosis. Seven patients with a clinical diagnosis of infectious mononucleosis (IM) and detectable heterophil antibodies were found to have peripheral blood lymphocytes that were cytotoxic for lymphoid cells containing Epstein-Barr virus from a patient with Burkitt's lymphoma. The cytotoxic lymphocytes persisted in the peripheral circulation for up to 45 days. Patients who had had IM 1 to 5 years previously lacked such cytotoxic lymphocytes. Patients who had signs and symptoms of IM but no detectable heterophil antibodies lacked cytotoxic lymphocytes. The lymphocytes of one patient with IM showed progressive diminution of cytotoxic ability after prednisone treatment."}
{"id": "PMID:187312", "title": "Combination chemotherapy of advanced lung cancer: a randomized trial.", "content": "A controlled clinical trial comparing two-drug and three-drug combination chemotherapy was performed in 206 patients with advanced bronchogenic carcinoma, comprised of 26.2% with epidermoid carcinoma, 30.1% with small cell anaplastic carcinoma, 27.2% with adenocarcinoma, and 15.6% with large cell carcinoma. Each drug combination consisted of agents with different modes of action and included a cell-cycle-stage nonsensitive and a cell-cycle-state-sensitive agent. The overall response rate was highest for small cell carcinoma (48.2%) and adenocarcinoma (23.6%); it was less than 10% in epidermoid and large cell carcinoma. Similarly, the overall median survival was twice as long for the first two cell types (7 months) as compared with that recorded for the other two cell types (3 1/2 months). The combination of 1 (2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cyclophosphamide, and methotrexate was shown to be statistically superior to cyclophosphamide and methotrexate with regard to objective respones rate, duration of response, and median survival for adenocarcinoma. Responders lived significantly longer than nonresponders (254 versus 90 days for small cell anaplastic carcinoma patients and 244 versus 184 days for adenocarcinoma patients). No difference in survival or objective response rate was observed between the different treatments for the other two cell types of lung cancer.", "contents": "Combination chemotherapy of advanced lung cancer: a randomized trial. A controlled clinical trial comparing two-drug and three-drug combination chemotherapy was performed in 206 patients with advanced bronchogenic carcinoma, comprised of 26.2% with epidermoid carcinoma, 30.1% with small cell anaplastic carcinoma, 27.2% with adenocarcinoma, and 15.6% with large cell carcinoma. Each drug combination consisted of agents with different modes of action and included a cell-cycle-stage nonsensitive and a cell-cycle-state-sensitive agent. The overall response rate was highest for small cell carcinoma (48.2%) and adenocarcinoma (23.6%); it was less than 10% in epidermoid and large cell carcinoma. Similarly, the overall median survival was twice as long for the first two cell types (7 months) as compared with that recorded for the other two cell types (3 1/2 months). The combination of 1 (2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cyclophosphamide, and methotrexate was shown to be statistically superior to cyclophosphamide and methotrexate with regard to objective respones rate, duration of response, and median survival for adenocarcinoma. Responders lived significantly longer than nonresponders (254 versus 90 days for small cell anaplastic carcinoma patients and 244 versus 184 days for adenocarcinoma patients). No difference in survival or objective response rate was observed between the different treatments for the other two cell types of lung cancer."}
{"id": "PMID:187313", "title": "Treatment of bronchogenic carcinoma with simultaneous or sequential combination chemotherapy, including methotrexate, cyclophosphamide, procarbazine and vincristine.", "content": "One hundred and eighteen patients with inoperable carcinoma of the lung were randomly selected for treatment with methotrexate, cyclophosphamide, procarbazine, and vincristine. These drugs were adminsitered simultaneously to one group of patients and sequentially to the second group. As the statistically sicame evident (51% vs. 21%), an additional 85 cases were treated in this manner without randomization. The objective clinical responses were associated with prolonged survival. A higher response rate with the simultaneous treatment was also evident in patients with anaplastic small cell carcinoma (65% vs. 36%) as well as those with epidermoid carcinoma (33% vs. 13%). These differences were not statistically significant. Toxicity remained within acceptable limits, with a 2% drug related mortality, and was similar in both treatment regimens. Initial performance status was definitely related to survival, but not to tumor response. Patients with epidermoid carcinomas showing stabilization of tumor growth under treatment had the longest survival. Maintenance therapy with continued four-drug polychemotherapy was not superior to single agent maintenance with cyclophosphamide.", "contents": "Treatment of bronchogenic carcinoma with simultaneous or sequential combination chemotherapy, including methotrexate, cyclophosphamide, procarbazine and vincristine. One hundred and eighteen patients with inoperable carcinoma of the lung were randomly selected for treatment with methotrexate, cyclophosphamide, procarbazine, and vincristine. These drugs were adminsitered simultaneously to one group of patients and sequentially to the second group. As the statistically sicame evident (51% vs. 21%), an additional 85 cases were treated in this manner without randomization. The objective clinical responses were associated with prolonged survival. A higher response rate with the simultaneous treatment was also evident in patients with anaplastic small cell carcinoma (65% vs. 36%) as well as those with epidermoid carcinoma (33% vs. 13%). These differences were not statistically significant. Toxicity remained within acceptable limits, with a 2% drug related mortality, and was similar in both treatment regimens. Initial performance status was definitely related to survival, but not to tumor response. Patients with epidermoid carcinomas showing stabilization of tumor growth under treatment had the longest survival. Maintenance therapy with continued four-drug polychemotherapy was not superior to single agent maintenance with cyclophosphamide."}
{"id": "PMID:187314", "title": "Combination chemotherapy in advanced lung cancer with increased survival.", "content": "Twenty-eight patients with lung cancer, 26 with extensive disease, were treated with the drugs Cytoxan (Cyt) and methotrexate (MTX). The schedule was based on cellular kinetics concepts. Initial therapy was with Cyt 1.1 g/m2 (intravenously) followed by MTX 20 mg/m2 orally, twice weekly, started 9 days later, when the tumor was considered to be most susceptible to an S-phase-specific drug. The course was repeated at three-week intervals. Based on dose response curves, Cyt and MTX dose modifications were individually adjusted to the whit blood cell counts and platelet counts over a 3-week period. Twenty of 28 patients (five of seven large cell, five of eight adenocarcinoma, 10 or 11 small cell, none of two epidermoid) responded with greater than or equal 50% tumor reduction. Ten patients had complete responses, seven of whom had small cell carcinoma. Two of the nonresponders were nonevaluable. Five patients were alive and the extimated median survival time of the patients is almost 1 year, which compares quite favorably to previous reports. On this schedule of therapy, very high doses of Cyt and MTX were maintained with less than 3% incidence per course of a WBC less than 1,500/mm3 or a platelet count less than 50,000/mm3.", "contents": "Combination chemotherapy in advanced lung cancer with increased survival. Twenty-eight patients with lung cancer, 26 with extensive disease, were treated with the drugs Cytoxan (Cyt) and methotrexate (MTX). The schedule was based on cellular kinetics concepts. Initial therapy was with Cyt 1.1 g/m2 (intravenously) followed by MTX 20 mg/m2 orally, twice weekly, started 9 days later, when the tumor was considered to be most susceptible to an S-phase-specific drug. The course was repeated at three-week intervals. Based on dose response curves, Cyt and MTX dose modifications were individually adjusted to the whit blood cell counts and platelet counts over a 3-week period. Twenty of 28 patients (five of seven large cell, five of eight adenocarcinoma, 10 or 11 small cell, none of two epidermoid) responded with greater than or equal 50% tumor reduction. Ten patients had complete responses, seven of whom had small cell carcinoma. Two of the nonresponders were nonevaluable. Five patients were alive and the extimated median survival time of the patients is almost 1 year, which compares quite favorably to previous reports. On this schedule of therapy, very high doses of Cyt and MTX were maintained with less than 3% incidence per course of a WBC less than 1,500/mm3 or a platelet count less than 50,000/mm3."}
{"id": "PMID:187315", "title": "Unusual postirradiation sarcoma of chest wall.", "content": "This paper reports a sarcoma of the chest wall following postoperative radiation therapy for breast carcinoma. A total of 9346 rads was delivered at a 2-cm tissue depth from two treatment courses separated by a five-year interval. The sarcoma appeared 16 years following the initial radiation course. The existence of two mesenchymal elements in the lesion led to the final diagnosis of malignant mesenchymoma. Criteria for evaluating a possible radiation-induced malignancy are discussed.", "contents": "Unusual postirradiation sarcoma of chest wall. This paper reports a sarcoma of the chest wall following postoperative radiation therapy for breast carcinoma. A total of 9346 rads was delivered at a 2-cm tissue depth from two treatment courses separated by a five-year interval. The sarcoma appeared 16 years following the initial radiation course. The existence of two mesenchymal elements in the lesion led to the final diagnosis of malignant mesenchymoma. Criteria for evaluating a possible radiation-induced malignancy are discussed."}
{"id": "PMID:187316", "title": "The immune response at the tumor site in lung carcinoma.", "content": "The local immune response to lung cancer was investigated by histologic and immunologic means. Distinctive patterns of stromal cellular reaction, characteristic for different histologic types of lung carcinoma, were recognized. The amount of cellular infiltration was highest in squamous cell carcinomas and lowest or nonexistent in oat cell carcinomas. Within the various histologic categories the well-differentiated tumors appeared to be accompanied by more reactive cells than the poorly differentiated ones; there was no relation between tumor necrosis and cellular infiltration. The plasma cells were distinctly associated with squamous cell carcinomas; their number in the stroma was proportionate to the degree of differentiation and the presence of keratin produced by the tumors. Eluates with a high content of immunoglobulins were recovered from pleural effusions and from solid lung carcinomas by dissociation of antigen-antibody complexes. These preparations reacted positively in indirect immunofluorescence tests with tissue cultures and with fresh suspensions of lung carcinoma cells, but not with tissue culture cells of most nonpulmonary tumors or with cell suspensions of normal adult and fetal lung. Similarly prepared fractions of noncarcinomatous pleural effusions did not react with lung cancer cells.", "contents": "The immune response at the tumor site in lung carcinoma. The local immune response to lung cancer was investigated by histologic and immunologic means. Distinctive patterns of stromal cellular reaction, characteristic for different histologic types of lung carcinoma, were recognized. The amount of cellular infiltration was highest in squamous cell carcinomas and lowest or nonexistent in oat cell carcinomas. Within the various histologic categories the well-differentiated tumors appeared to be accompanied by more reactive cells than the poorly differentiated ones; there was no relation between tumor necrosis and cellular infiltration. The plasma cells were distinctly associated with squamous cell carcinomas; their number in the stroma was proportionate to the degree of differentiation and the presence of keratin produced by the tumors. Eluates with a high content of immunoglobulins were recovered from pleural effusions and from solid lung carcinomas by dissociation of antigen-antibody complexes. These preparations reacted positively in indirect immunofluorescence tests with tissue cultures and with fresh suspensions of lung carcinoma cells, but not with tissue culture cells of most nonpulmonary tumors or with cell suspensions of normal adult and fetal lung. Similarly prepared fractions of noncarcinomatous pleural effusions did not react with lung cancer cells."}
{"id": "PMID:187317", "title": "Vagal body tumor (nonchromaffin paraganglioma, chemodectoma, and carotid body-like tumor) with cervical node metastasis and familial association: ultrastructural study and review.", "content": "A case of a vagal body tumor with a solitary cervical node metastasis is described. There was a remarkable familial association: a biopsy-proven paraganglioma occurred in two members of the patient's family and there was a strong clinical suspicion of a paraganglioma in two others. In a review of the literature, eight patients with metastasizing vagal body tumors and eight patients in whom the vagal body tumor was a component of multicentric presentation of paragangliomas were found. Only one other patient in whom there was a familial occurrence involving a vagal body tumor has been reported. Ultrastructural study of the cervical node metastasis revealed the presence of light and dark chief cells containing scanty, membrane-bound, densecore, neurosecretory-type granules. Atypical granules were noted in a few of the dark cells. Nerve fibers, synaptic vesicles, and sustentacular cells, such as occur in normal paraganglionic tissue, were not observed in this tumor.", "contents": "Vagal body tumor (nonchromaffin paraganglioma, chemodectoma, and carotid body-like tumor) with cervical node metastasis and familial association: ultrastructural study and review. A case of a vagal body tumor with a solitary cervical node metastasis is described. There was a remarkable familial association: a biopsy-proven paraganglioma occurred in two members of the patient's family and there was a strong clinical suspicion of a paraganglioma in two others. In a review of the literature, eight patients with metastasizing vagal body tumors and eight patients in whom the vagal body tumor was a component of multicentric presentation of paragangliomas were found. Only one other patient in whom there was a familial occurrence involving a vagal body tumor has been reported. Ultrastructural study of the cervical node metastasis revealed the presence of light and dark chief cells containing scanty, membrane-bound, densecore, neurosecretory-type granules. Atypical granules were noted in a few of the dark cells. Nerve fibers, synaptic vesicles, and sustentacular cells, such as occur in normal paraganglionic tissue, were not observed in this tumor."}
{"id": "PMID:187318", "title": "Carcinoma of supernumerary breast of vulva with bilateral mammary cancer.", "content": "Primary mammary cancer often develops at multiple sites in either one or both breasts, evidently the result of a common carcinogen acting in multicentric loci. The occurrence of carcinoma in accessory breast tissue has been recorded, including carcinoma in supernumerary breast tissue within the labium, although the latter is rare. A 62-year-old woman developed carcinoma of the right breast which was followed nearly five and one half years later by the occurrence of adenocarcinoma in supernumerary breast tissue within the left labium majus. Concomitantly, carcinoma was detected in the left breast. The three cancers exhibited histologic features compatible with primary rather than metastatic lesions. The development of primary carcinoma in both breasts as well as within ectopic mammary tissue in the labium appears to be the first recorded instance of such an event.", "contents": "Carcinoma of supernumerary breast of vulva with bilateral mammary cancer. Primary mammary cancer often develops at multiple sites in either one or both breasts, evidently the result of a common carcinogen acting in multicentric loci. The occurrence of carcinoma in accessory breast tissue has been recorded, including carcinoma in supernumerary breast tissue within the labium, although the latter is rare. A 62-year-old woman developed carcinoma of the right breast which was followed nearly five and one half years later by the occurrence of adenocarcinoma in supernumerary breast tissue within the left labium majus. Concomitantly, carcinoma was detected in the left breast. The three cancers exhibited histologic features compatible with primary rather than metastatic lesions. The development of primary carcinoma in both breasts as well as within ectopic mammary tissue in the labium appears to be the first recorded instance of such an event."}
{"id": "PMID:187319", "title": "Two cases of multiple hormone-producing small cell carcinoma of the lung: coexistence of tumor ADH, ACTH, and beta-MSH.", "content": "Two cases of small cell carcinoma of the lung associated with the ectopic production of multiple hormones are reported. Both tumors were shown to contain significant amounts of ADH, ACTH, and beta-MSH. Biologic, immunologic, and gel chromatographic properties of these ectopic hormones were found to be very similar to those of pituitary origin. The effect of excessive secretion of antidiuretic hormone (ADH) dominated the clinical manifestations in both cases, i.e., syndrome of inappropriate secretion of ADH (SIADH). The clinical manifestations of the ectopic ACTH-MSH syndrome were minimal. These data suggest that multiple hormone production without clinically overt sequelae of excess hormone is not uncommon in small cell (oat cell) carcinoma of the lung.", "contents": "Two cases of multiple hormone-producing small cell carcinoma of the lung: coexistence of tumor ADH, ACTH, and beta-MSH. Two cases of small cell carcinoma of the lung associated with the ectopic production of multiple hormones are reported. Both tumors were shown to contain significant amounts of ADH, ACTH, and beta-MSH. Biologic, immunologic, and gel chromatographic properties of these ectopic hormones were found to be very similar to those of pituitary origin. The effect of excessive secretion of antidiuretic hormone (ADH) dominated the clinical manifestations in both cases, i.e., syndrome of inappropriate secretion of ADH (SIADH). The clinical manifestations of the ectopic ACTH-MSH syndrome were minimal. These data suggest that multiple hormone production without clinically overt sequelae of excess hormone is not uncommon in small cell (oat cell) carcinoma of the lung."}
{"id": "PMID:187320", "title": "Reaction of antigens isolated from herpes simplex virus-transformed cells with sera of squamous cell carcinoma patients.", "content": "Antigens isolated from herpes simplex virus type 1, herpes simplex virus type 2, or cytomegalovirus-transformed hamster cells were tested against 66 sera from non-cancer individuals or patients with different types of cancer. By use of the microcomplement fixation procedure to quantify all antigen-antibody interactions, it was observed that 94% (p less than 0.001) of all sera from patients with squamous cell carcinoma reacted with antigens from herpes simplex virus type 1-transformed cells, while 84% (p less than 0.001) of the same sera reacted with antigen preparations from herpes simplex virus type 2-transformed cells. When sera from patients with adenocarcinoma, sarcoma, liposarcoma, and melanoma were tested against these antigens, there was no significant difference in their reactivity from sera of noncancer patients. When sera from all individuals (normal and cancer) were tested against antigens from cytomegalovirus-transformed cells, no significant reaction pattern developed. These studies are the first to describe the isolation of a reactive tumor-associated protein from herpes simplex virus-transformed cells.", "contents": "Reaction of antigens isolated from herpes simplex virus-transformed cells with sera of squamous cell carcinoma patients. Antigens isolated from herpes simplex virus type 1, herpes simplex virus type 2, or cytomegalovirus-transformed hamster cells were tested against 66 sera from non-cancer individuals or patients with different types of cancer. By use of the microcomplement fixation procedure to quantify all antigen-antibody interactions, it was observed that 94% (p less than 0.001) of all sera from patients with squamous cell carcinoma reacted with antigens from herpes simplex virus type 1-transformed cells, while 84% (p less than 0.001) of the same sera reacted with antigen preparations from herpes simplex virus type 2-transformed cells. When sera from patients with adenocarcinoma, sarcoma, liposarcoma, and melanoma were tested against these antigens, there was no significant difference in their reactivity from sera of noncancer patients. When sera from all individuals (normal and cancer) were tested against antigens from cytomegalovirus-transformed cells, no significant reaction pattern developed. These studies are the first to describe the isolation of a reactive tumor-associated protein from herpes simplex virus-transformed cells."}
{"id": "PMID:187321", "title": "Inhibition of tumor cell growth in vitro and in vivo by 1-beta-D-arabinofuranosylcytosine entrapped within phospholipid vesicles.", "content": "Phospholipid vesicles have been used as a carrier vehicle to enhance the cytotoxic activity of 1-beta-D-arabinofuranosyl-cytosine (ara-C) and 1-beta-D-arabinofuranosylcytosine 5'-triphosphate against several tumor cell lines. The activity of both compounds in free solution or entrapped within phospholipid vesicles was compared against L1210 cells, Ehrlich ascites cells, and SV40-transformed 3T3 cells in vitro. In addition, the activity of vesicle-entrapped ara-C against L1210 cells was also studied in vivo. The results obtained in vitro with ara-C indicated no difference in the concentration needed to inhibit growth of cells by 50% between free ara-C and vesicle-entrapped ara-C. In contrast, 1-beta-D-arabinofuranosylcytosine 5'-triphosphate entrapped in phospholipid vesicles was a more potent inhibitor of L1210 in culture (ID50, 2 X 10(-8) M) compared to the relatively inactive free 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (id50 greater than 10(-7) M). Experiments carried out with L1210 cells in mice showed that, after a single i.p. dose (10 mg/kg) of vesicle-entrapped ara-C, the average survival times of mice inoculated with 10(5) L1210 cells were increased by over 90%. In control experiments, free ara-C or vesicles plus free ara-C (10 mg/kg) did not prolong survival of mice.", "contents": "Inhibition of tumor cell growth in vitro and in vivo by 1-beta-D-arabinofuranosylcytosine entrapped within phospholipid vesicles. Phospholipid vesicles have been used as a carrier vehicle to enhance the cytotoxic activity of 1-beta-D-arabinofuranosyl-cytosine (ara-C) and 1-beta-D-arabinofuranosylcytosine 5'-triphosphate against several tumor cell lines. The activity of both compounds in free solution or entrapped within phospholipid vesicles was compared against L1210 cells, Ehrlich ascites cells, and SV40-transformed 3T3 cells in vitro. In addition, the activity of vesicle-entrapped ara-C against L1210 cells was also studied in vivo. The results obtained in vitro with ara-C indicated no difference in the concentration needed to inhibit growth of cells by 50% between free ara-C and vesicle-entrapped ara-C. In contrast, 1-beta-D-arabinofuranosylcytosine 5'-triphosphate entrapped in phospholipid vesicles was a more potent inhibitor of L1210 in culture (ID50, 2 X 10(-8) M) compared to the relatively inactive free 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (id50 greater than 10(-7) M). Experiments carried out with L1210 cells in mice showed that, after a single i.p. dose (10 mg/kg) of vesicle-entrapped ara-C, the average survival times of mice inoculated with 10(5) L1210 cells were increased by over 90%. In control experiments, free ara-C or vesicles plus free ara-C (10 mg/kg) did not prolong survival of mice."}
{"id": "PMID:187322", "title": "Subcellular localization of acetoacetate coenzyme A transferase in rat hepatomas.", "content": "Succinyl coenzyme A:acetoacetate coenzyme transferase (EC 2.8.3.5), an initiator of ketone body usage and absent in normal liver, has been shown to be located in mitochondria from Morris hepatoma 7288ctc using differential and density gradient centrifugation. Furthermore, tumor mitochondrial subfractionation revealed that this transferase is associated with the matrix-soluble proteins. Comparison of the amounts of total transferase activity in several other hepatomas with the amounts found in the corresponding isolated mitochondria suggests that the results with the 7288ctc tumor pertain generally. The mitochondrial localization of coenzyme A transferase indicates the probable use of ketone bodies as energy sources for the hepatomas.", "contents": "Subcellular localization of acetoacetate coenzyme A transferase in rat hepatomas. Succinyl coenzyme A:acetoacetate coenzyme transferase (EC 2.8.3.5), an initiator of ketone body usage and absent in normal liver, has been shown to be located in mitochondria from Morris hepatoma 7288ctc using differential and density gradient centrifugation. Furthermore, tumor mitochondrial subfractionation revealed that this transferase is associated with the matrix-soluble proteins. Comparison of the amounts of total transferase activity in several other hepatomas with the amounts found in the corresponding isolated mitochondria suggests that the results with the 7288ctc tumor pertain generally. The mitochondrial localization of coenzyme A transferase indicates the probable use of ketone bodies as energy sources for the hepatomas."}
{"id": "PMID:187323", "title": "Morphological evidence for the translocation of lysosomal organelles from cytotoxic macrophages into the cytoplasm of tumor target cells.", "content": "In this study we have recorded in detail the morphological sequence of interactions between activated macrophages and tumor target cells in vitro. The study is unique because it involves the combination of several microscopic techniques that are used sequentially to study a single cell-to-cell interaction. Many such cellular interactions were examined first by time lapse cinematography; then the effector cell was identified by specific immunofluorescence, and the areas of interaction were processed for scanning and then transmission electron microscopy. The tumor target cells were guinea pig line 10 hepatocarcinoma cells. The effectors were peritoneal exudate cells (PEC) harvested from syngeneic strain 2 guinea pigs that had been cured of a line 10 tumor by intratumoral injection of Bacillus Calmette-Gu\u00e9rin. Host-target cell interactions between (a) line 10 cells and PEC from Bacillus Calmette Gu\u00e9rin-tumor-cured animals, (b) line 10 cells and PEC from normal animals and (c) syngeneic guinea pig embryo cells and PEC from Bacillus Calmette-Gu\u00e9rin-tumor-cured animals were studied. These comparisons demonstrate that the mechanism of tumor cell killing by activated macrophages is a nonphagocytic process. Our results suggested that the macrophage-tumor cell interaction is initiated by a recognition phase that results in extracellular release of lysosomes through macrophage exocytosis and clasmatosis. Neoplastic target cell susceptibility may be the result of an active or passive uptake of lysosomes and consequently cytolysis.", "contents": "Morphological evidence for the translocation of lysosomal organelles from cytotoxic macrophages into the cytoplasm of tumor target cells. In this study we have recorded in detail the morphological sequence of interactions between activated macrophages and tumor target cells in vitro. The study is unique because it involves the combination of several microscopic techniques that are used sequentially to study a single cell-to-cell interaction. Many such cellular interactions were examined first by time lapse cinematography; then the effector cell was identified by specific immunofluorescence, and the areas of interaction were processed for scanning and then transmission electron microscopy. The tumor target cells were guinea pig line 10 hepatocarcinoma cells. The effectors were peritoneal exudate cells (PEC) harvested from syngeneic strain 2 guinea pigs that had been cured of a line 10 tumor by intratumoral injection of Bacillus Calmette-Gu\u00e9rin. Host-target cell interactions between (a) line 10 cells and PEC from Bacillus Calmette Gu\u00e9rin-tumor-cured animals, (b) line 10 cells and PEC from normal animals and (c) syngeneic guinea pig embryo cells and PEC from Bacillus Calmette-Gu\u00e9rin-tumor-cured animals were studied. These comparisons demonstrate that the mechanism of tumor cell killing by activated macrophages is a nonphagocytic process. Our results suggested that the macrophage-tumor cell interaction is initiated by a recognition phase that results in extracellular release of lysosomes through macrophage exocytosis and clasmatosis. Neoplastic target cell susceptibility may be the result of an active or passive uptake of lysosomes and consequently cytolysis."}
{"id": "PMID:187324", "title": "A comparison of in vitro cell-mediated reactivity against syngeneic tumor cells by various lymphoid cell populations from Bacillus Calmette-Gu\u00e9rin-tumor-cured, tumor-sensitized, tumor-bearing, and normal inbred guinea pigs.", "content": "The cell-mediated reactivity (CMR) in vitro of normal, line 10 hepatocardinoma tumor-bearing, Bacillus Calmette Gu\u00e9rin (BCG)-line 10 tumor-cured, and line 1 sensitized guinea pigs against synegeneic line 10 hepatocarcinma was measured. This study was designed to determine whether the in vitro CMR correlates with the clinical stage of disease in a guinea pig immunotherapy model. A comparison was also made between the CMR of effector cells from active regional lymph nodes, pooled distant lymph nodes and spleen non-glass-adherent mononuclear cells (lymphocytes), peritoneal exudate macrophages (PEM), and peripheral blood leukocytes. In addition, the immunological specificity of the in vitro cytotoxicity was investigated by comparing the reactivities against line 10 and the highly antigenic syngeneic line 1 hepatocarcinoma as well as normal syngeneic guinea pig embryo cells. Pooled lymphocytes and PEM from normal guinea pigs were cytotoxic to line 1 hepatocarcinoma cells but not to line 10 hepatocarcinoma cells. Pooled lymphocytes and PEM obtained from animals sensitized in vivo to line 1 tumor exhibited in vitro cytotoxicity against line 1 cells, which was comparable to that cytotoxicity obtained from normal, naive donors. Various effector cells from BCG-tumor-cured guinea pigs destroyed line 10 cells but to different degrees. In the order of their decreasing cytotoxic effect against line 10 cells, the effector cells from BCG-tumor-cured guinea pigs were: glass-adherent regional lymph node cells and PEM, followed by non-glass-adherent regional lymph node cells, peripheral blood leukocytes, and pooled spleen and lymph node lymphocytes. Effector cells obtained from animals bearing line 10 tumors were all cytotoxic in vitro against line 10 cells. There were no qualitative differences in CMR between effector cells of tumor-bearing and BCG-tumor-cured guinea pigs. Although some quantitative differences between tumor-bearing and tumor-cured guinea pigs were observed, these differences were not large enough to reliably predict the clinical status of the donor in a blind test.", "contents": "A comparison of in vitro cell-mediated reactivity against syngeneic tumor cells by various lymphoid cell populations from Bacillus Calmette-Gu\u00e9rin-tumor-cured, tumor-sensitized, tumor-bearing, and normal inbred guinea pigs. The cell-mediated reactivity (CMR) in vitro of normal, line 10 hepatocardinoma tumor-bearing, Bacillus Calmette Gu\u00e9rin (BCG)-line 10 tumor-cured, and line 1 sensitized guinea pigs against synegeneic line 10 hepatocarcinma was measured. This study was designed to determine whether the in vitro CMR correlates with the clinical stage of disease in a guinea pig immunotherapy model. A comparison was also made between the CMR of effector cells from active regional lymph nodes, pooled distant lymph nodes and spleen non-glass-adherent mononuclear cells (lymphocytes), peritoneal exudate macrophages (PEM), and peripheral blood leukocytes. In addition, the immunological specificity of the in vitro cytotoxicity was investigated by comparing the reactivities against line 10 and the highly antigenic syngeneic line 1 hepatocarcinoma as well as normal syngeneic guinea pig embryo cells. Pooled lymphocytes and PEM from normal guinea pigs were cytotoxic to line 1 hepatocarcinoma cells but not to line 10 hepatocarcinoma cells. Pooled lymphocytes and PEM obtained from animals sensitized in vivo to line 1 tumor exhibited in vitro cytotoxicity against line 1 cells, which was comparable to that cytotoxicity obtained from normal, naive donors. Various effector cells from BCG-tumor-cured guinea pigs destroyed line 10 cells but to different degrees. In the order of their decreasing cytotoxic effect against line 10 cells, the effector cells from BCG-tumor-cured guinea pigs were: glass-adherent regional lymph node cells and PEM, followed by non-glass-adherent regional lymph node cells, peripheral blood leukocytes, and pooled spleen and lymph node lymphocytes. Effector cells obtained from animals bearing line 10 tumors were all cytotoxic in vitro against line 10 cells. There were no qualitative differences in CMR between effector cells of tumor-bearing and BCG-tumor-cured guinea pigs. Although some quantitative differences between tumor-bearing and tumor-cured guinea pigs were observed, these differences were not large enough to reliably predict the clinical status of the donor in a blind test."}
{"id": "PMID:187325", "title": "Thymidylate synthetase activity in the Novikoff hepatoma.", "content": "The mechanism by which injected methotrexate increases thymidylate synthetase activity in the Novikoff hepatoma has been studied. Folic acid injection causes a similar increase in enzyme activity in hepatoma after 16 hr but the action of folic acid and methotrexate is not additive. The increase in activity of thymidine 5'-phosphate synthetase in the hepatoma caused by methotrexate is not affected by actinomycin D, but is inhibited 50% by puromycin and 100% by cycloheximide. High-speed supernatent fraction prepared from hepatoma of animals treated with methotrexate has, initially, one-half the specific thymidine 5'-phosphate synthetase activity of untreated controls. Upon addition of increasing amounts of tetrahydrofolate, the specific enzyme activity in the supernatant fraction from the methotrexate-treated animals rises to double that of the controls. Puromycin added to homogenates of Novikoff hepatoma consistently increases enzyme activity by approximately 20%. One hypothesis consistent with these results and results reported by others is presented.", "contents": "Thymidylate synthetase activity in the Novikoff hepatoma. The mechanism by which injected methotrexate increases thymidylate synthetase activity in the Novikoff hepatoma has been studied. Folic acid injection causes a similar increase in enzyme activity in hepatoma after 16 hr but the action of folic acid and methotrexate is not additive. The increase in activity of thymidine 5'-phosphate synthetase in the hepatoma caused by methotrexate is not affected by actinomycin D, but is inhibited 50% by puromycin and 100% by cycloheximide. High-speed supernatent fraction prepared from hepatoma of animals treated with methotrexate has, initially, one-half the specific thymidine 5'-phosphate synthetase activity of untreated controls. Upon addition of increasing amounts of tetrahydrofolate, the specific enzyme activity in the supernatant fraction from the methotrexate-treated animals rises to double that of the controls. Puromycin added to homogenates of Novikoff hepatoma consistently increases enzyme activity by approximately 20%. One hypothesis consistent with these results and results reported by others is presented."}
{"id": "PMID:187326", "title": "Abnormal ultrastructural changes in sodium periodate-stimulated lymphocytes from patients with chronic lymphocytic leukemia.", "content": "Lymphocytoid and plasmacytoid blasts have been identified in both normal and chronic lymphocytic leukemia lymphocyte cultures exposed to NaIO4. However, the appearance of ultrastructurally abnormal blasts in chronic lymphocytic leukemia cultures suggests that NaIO4 also stimulates the transformation of an abnormal subpopulation of lymphocytes. Development of invaginated nuclei produced morphological features similar to nuclear blebs, a cellular abnormally described in blood cells from other cancers. Furthermore, the consistent localization of nuclear invagination only to portions of nuclei adjacent to developing cytoplasmic microtublar complexes suggests a role for microtubules in the transformation process. The absence of these unusual blasts in cultures stimulated with other mitogens may indicate that these NaIO4-sensitive cells are not responsive to the more commonly used plant lectins.", "contents": "Abnormal ultrastructural changes in sodium periodate-stimulated lymphocytes from patients with chronic lymphocytic leukemia. Lymphocytoid and plasmacytoid blasts have been identified in both normal and chronic lymphocytic leukemia lymphocyte cultures exposed to NaIO4. However, the appearance of ultrastructurally abnormal blasts in chronic lymphocytic leukemia cultures suggests that NaIO4 also stimulates the transformation of an abnormal subpopulation of lymphocytes. Development of invaginated nuclei produced morphological features similar to nuclear blebs, a cellular abnormally described in blood cells from other cancers. Furthermore, the consistent localization of nuclear invagination only to portions of nuclei adjacent to developing cytoplasmic microtublar complexes suggests a role for microtubules in the transformation process. The absence of these unusual blasts in cultures stimulated with other mitogens may indicate that these NaIO4-sensitive cells are not responsive to the more commonly used plant lectins."}
{"id": "PMID:187327", "title": "Isolation and localization of RNA fractions able to transfer tumor-specific delayed hypersensitivity in vitro.", "content": "RNA fractions were prepared by sucrose density gradient centrifugation from hot-cold phenol, RNA-rich extracts of lymphoid tissues from strain 2 guinea pigs hyperimmunized to line 1 or line 10 tumors. Each RNA fraction was assessed for its ability to convert nonsensitized strain 2 peritoneal exudate cells to a state of specific sensitivity for line 1- or line 10-solubilized tumor antigens. An RNA fraction residing between the 4 S and 18 S peaks, designated as Fraction \"B\", transferred line 10 or line 1 sensitivity in 12 experiments. Twelve additional RNA extracts containing 2 subfractions prepared from RNA fraction B, designated as B1 and B2, also transferred line 1 or line 10 sensitivity in 14 experiments. Except for 3 experiments where the 4 S or 18 S material transferred tumor-specific sensitivity, RNA fractions corresponding to approximately 4 S, 18 S, 22 S, and 28 S were unable to transfer tumor-specific sensitivity to nonsensitized peritoneal exudate cells. Treatment of fraction B with RNase results in complete loss of ability to transfer immunobiological activity.", "contents": "Isolation and localization of RNA fractions able to transfer tumor-specific delayed hypersensitivity in vitro. RNA fractions were prepared by sucrose density gradient centrifugation from hot-cold phenol, RNA-rich extracts of lymphoid tissues from strain 2 guinea pigs hyperimmunized to line 1 or line 10 tumors. Each RNA fraction was assessed for its ability to convert nonsensitized strain 2 peritoneal exudate cells to a state of specific sensitivity for line 1- or line 10-solubilized tumor antigens. An RNA fraction residing between the 4 S and 18 S peaks, designated as Fraction \"B\", transferred line 10 or line 1 sensitivity in 12 experiments. Twelve additional RNA extracts containing 2 subfractions prepared from RNA fraction B, designated as B1 and B2, also transferred line 1 or line 10 sensitivity in 14 experiments. Except for 3 experiments where the 4 S or 18 S material transferred tumor-specific sensitivity, RNA fractions corresponding to approximately 4 S, 18 S, 22 S, and 28 S were unable to transfer tumor-specific sensitivity to nonsensitized peritoneal exudate cells. Treatment of fraction B with RNase results in complete loss of ability to transfer immunobiological activity."}
{"id": "PMID:187328", "title": "Independent alterations in cell shape and intramembranous particle topography induced by cytochalasin B and colchicine in normal and transformed cells.", "content": "Native differences in cell shape and plasma membrane organization in contact-inhibited and transformed cells and the effects of cytochalasin B and colchicine on these cells have been examined by scanning electron microscopy and freeze fracture-electron microscopy. Confluent BALB/c 3T3 cells show a flat, polygonal shape with limited cell overlapping, some microvilli, and plasma membranes with an aggregated distribution of intramembranous particles. Simian virus 40-transformed BALB/c 3T3 cells, by contrast, have a pleomorphic, bipolar spindle shape, extensive cell overlapping, more numerous surface projections, and a random distribution of intramembranous particles. Treatment of 3T3 and SV3T3 cells with 10(-6) M colchicine produced changes in cell shape and induced intramembranous particle aggregation in SV3T3 cells but did not significantly affect the freeze fracture morphology of 3T3 plasma membranes. Treatment of 3T3 and SV3T3 cells with cytochalasin B (1 mug/ml) also produced marked changes in cell shape and induced intramembranous particle disaggregation in 3T3 cells, but it did not affect intramembranous particle distribution in SV3T3 cells. Lower doses of colchicine (10(-9) M) or cytochalasin B (1 to 50 ng) modulated intramembranous particle distribution in transformed and normal 3T3 cells, respectively, without seriously affecting cell shape. These results are interpreted to suggest that modulation of cell shape or cell surface topography and intramembranous particle distribution are separable phenomena.", "contents": "Independent alterations in cell shape and intramembranous particle topography induced by cytochalasin B and colchicine in normal and transformed cells. Native differences in cell shape and plasma membrane organization in contact-inhibited and transformed cells and the effects of cytochalasin B and colchicine on these cells have been examined by scanning electron microscopy and freeze fracture-electron microscopy. Confluent BALB/c 3T3 cells show a flat, polygonal shape with limited cell overlapping, some microvilli, and plasma membranes with an aggregated distribution of intramembranous particles. Simian virus 40-transformed BALB/c 3T3 cells, by contrast, have a pleomorphic, bipolar spindle shape, extensive cell overlapping, more numerous surface projections, and a random distribution of intramembranous particles. Treatment of 3T3 and SV3T3 cells with 10(-6) M colchicine produced changes in cell shape and induced intramembranous particle aggregation in SV3T3 cells but did not significantly affect the freeze fracture morphology of 3T3 plasma membranes. Treatment of 3T3 and SV3T3 cells with cytochalasin B (1 mug/ml) also produced marked changes in cell shape and induced intramembranous particle disaggregation in 3T3 cells, but it did not affect intramembranous particle distribution in SV3T3 cells. Lower doses of colchicine (10(-9) M) or cytochalasin B (1 to 50 ng) modulated intramembranous particle distribution in transformed and normal 3T3 cells, respectively, without seriously affecting cell shape. These results are interpreted to suggest that modulation of cell shape or cell surface topography and intramembranous particle distribution are separable phenomena."}
{"id": "PMID:187329", "title": "Imbalance of purine metabolism in hepatomas of different growth rates as expressed in behavior of xanthine oxidase (EC 1.2.3.2).", "content": "The behavior of the rate-limiting enzyme of purine catabolism, xanthine oxidase (EC 1.2.3.2); was examined in normal liver, in 17 hepatomas of different growth rates, and in rapidly growing differentiating and regenerating liver. Xanthine oxidase activity was measured in the supernatant fluid prepared by centrifugation of 5% homogenates at 100,000  X g for 30 min. There was no uricase activity in the supernatant fluid. The affinity of xanthine oxidase to xanthine was similar in normal liver and in slow- and rapidly growing hepatomas (Km=6 to 8 muM), and theoptimum pH was 8.0; at pH 7.4, the activity was 80% of that at the pH optimum. A standard assay was worked out for the liver and hepatoma systems; the enzyme activity was linear during 60-min incubation and proportionate with amounts of protein added over a range of 0.5 to 3.0 mg. Xanthine oxidase specific activity was 9 times higher in small intestine than in liver. Activities in lung, spleen, kidney, heart, testes, and thymus were 67, 59, 21, 19, 8, and 8%, and in skeletal muscle, brain, and bone marrow activities were 5% of that of the liver. In regenerating liver, xanthine oxidase activity was not changed from that of the liver of sham-operated controls up to 96 hr after operation. The activity of the average differentiating liver cell was less than 5% of that of adult liver during the first week after birth. At postnatal ages of 18, 25, 30 and 40 days, the activity rose to 18, 46, 76, and 94%, respectively, of that of the adult liver. In starvation, hepatic xanthine oxidase activity per cell was preferentially depleted as compared to the decline in protein concentration. Upon refeeding, the enzymatic activity was restored more slowly than the protein content. Since xanthine oxidase activity was decreased in all examined hepatomas, including the slowest-growing, well-differentiated neoplasms, the altered activity of this enzyme appears to be.linked with neoplastic transformatiobosyl 1-pyrophosphate amidotransferase (EC 2.4.2.14), was increassed in the hepatomas, the reprogramming of gene expression results in an imbalance that favors the synthetic over the catabolic potential. This enzymatic imbalance should confer selective advantages to the cancer cells.", "contents": "Imbalance of purine metabolism in hepatomas of different growth rates as expressed in behavior of xanthine oxidase (EC 1.2.3.2). The behavior of the rate-limiting enzyme of purine catabolism, xanthine oxidase (EC 1.2.3.2); was examined in normal liver, in 17 hepatomas of different growth rates, and in rapidly growing differentiating and regenerating liver. Xanthine oxidase activity was measured in the supernatant fluid prepared by centrifugation of 5% homogenates at 100,000  X g for 30 min. There was no uricase activity in the supernatant fluid. The affinity of xanthine oxidase to xanthine was similar in normal liver and in slow- and rapidly growing hepatomas (Km=6 to 8 muM), and theoptimum pH was 8.0; at pH 7.4, the activity was 80% of that at the pH optimum. A standard assay was worked out for the liver and hepatoma systems; the enzyme activity was linear during 60-min incubation and proportionate with amounts of protein added over a range of 0.5 to 3.0 mg. Xanthine oxidase specific activity was 9 times higher in small intestine than in liver. Activities in lung, spleen, kidney, heart, testes, and thymus were 67, 59, 21, 19, 8, and 8%, and in skeletal muscle, brain, and bone marrow activities were 5% of that of the liver. In regenerating liver, xanthine oxidase activity was not changed from that of the liver of sham-operated controls up to 96 hr after operation. The activity of the average differentiating liver cell was less than 5% of that of adult liver during the first week after birth. At postnatal ages of 18, 25, 30 and 40 days, the activity rose to 18, 46, 76, and 94%, respectively, of that of the adult liver. In starvation, hepatic xanthine oxidase activity per cell was preferentially depleted as compared to the decline in protein concentration. Upon refeeding, the enzymatic activity was restored more slowly than the protein content. Since xanthine oxidase activity was decreased in all examined hepatomas, including the slowest-growing, well-differentiated neoplasms, the altered activity of this enzyme appears to be.linked with neoplastic transformatiobosyl 1-pyrophosphate amidotransferase (EC 2.4.2.14), was increassed in the hepatomas, the reprogramming of gene expression results in an imbalance that favors the synthetic over the catabolic potential. This enzymatic imbalance should confer selective advantages to the cancer cells."}
{"id": "PMID:187330", "title": "DNA synthesis inpermeable mouse ascites sarcoma cells.", "content": "DNA synthesis was studied in mouse ascites sarcoma cells using a permeable cell system. The sarcoma was induced by the Schmidt-Ruppin strain of Rous sarcoma virus. The cells were made permeable to nucleoside triphosphates by treatment with a hypotonic buffer containing 10 mM Tris Cl, 4 mM MgCl2, 1 mM EDTA, and 6 mM 2-mercaptoethanol (pH 8.0). DNA-synthetic activity in the permeable cells was highly dependent on four deoxyribonucleoside triphosphates, adenosine triphosphates, Mg2+, and a proper ionic environment. The activity was stimulated about 50% by the addition of an appropriate concentration of cytidine triphosphate, guanosine triphosphate, and uridine triphosphate in an assay mixture containing adenosine triphosphate and four deoxyribonucleoside triphosphates. DNA synthesis was confined to the nucleus and was sensitive to N-ethylmaleimide and DNase. The activity assayed by the permeable cell system correlated closely with the DNA-replicating activity assayed by [3H]deoxythymidine incorporation in intact cells. The close correlation between DNA synthesis in vitro and in vivo was further confirmed in cultured sarcoma cells synchronized with DNA synthesis. Analysis of the DNA synthesized in vitro by alkaline cesium sulfate density gradient centrifugation showed that over half the DNA synthesized in permeable cells was due to elongation of strands initiated in vivo. The permeable cell system appears to be a useful method for examining DNA replication of cells in suspensions.", "contents": "DNA synthesis inpermeable mouse ascites sarcoma cells. DNA synthesis was studied in mouse ascites sarcoma cells using a permeable cell system. The sarcoma was induced by the Schmidt-Ruppin strain of Rous sarcoma virus. The cells were made permeable to nucleoside triphosphates by treatment with a hypotonic buffer containing 10 mM Tris Cl, 4 mM MgCl2, 1 mM EDTA, and 6 mM 2-mercaptoethanol (pH 8.0). DNA-synthetic activity in the permeable cells was highly dependent on four deoxyribonucleoside triphosphates, adenosine triphosphates, Mg2+, and a proper ionic environment. The activity was stimulated about 50% by the addition of an appropriate concentration of cytidine triphosphate, guanosine triphosphate, and uridine triphosphate in an assay mixture containing adenosine triphosphate and four deoxyribonucleoside triphosphates. DNA synthesis was confined to the nucleus and was sensitive to N-ethylmaleimide and DNase. The activity assayed by the permeable cell system correlated closely with the DNA-replicating activity assayed by [3H]deoxythymidine incorporation in intact cells. The close correlation between DNA synthesis in vitro and in vivo was further confirmed in cultured sarcoma cells synchronized with DNA synthesis. Analysis of the DNA synthesized in vitro by alkaline cesium sulfate density gradient centrifugation showed that over half the DNA synthesized in permeable cells was due to elongation of strands initiated in vivo. The permeable cell system appears to be a useful method for examining DNA replication of cells in suspensions."}
{"id": "PMID:187331", "title": "Aflatoxin B1-2,3-oxide as a probable intermediate in the covalent binding of aflatoxins B1 and B2 to rat liver DNA and ribosomal RNA in vivo.", "content": "Administration of[3H]aflatoxin B2 (2,3-dihydroaflatoxin B1)(AFB2) to male rats resulted in levels of hepatic DNA- and ribosomal(r)RNA-aflatoxin adducts that were about 1% of those for rats given [3H]aflatoxin B1(AFB1). The levels of hepatic protein-aflatoxin adducts were 35 to 70% as great for AFB2-treated as compared to AFB1-treated rats...", "contents": "Aflatoxin B1-2,3-oxide as a probable intermediate in the covalent binding of aflatoxins B1 and B2 to rat liver DNA and ribosomal RNA in vivo. Administration of[3H]aflatoxin B2 (2,3-dihydroaflatoxin B1)(AFB2) to male rats resulted in levels of hepatic DNA- and ribosomal(r)RNA-aflatoxin adducts that were about 1% of those for rats given [3H]aflatoxin B1(AFB1). The levels of hepatic protein-aflatoxin adducts were 35 to 70% as great for AFB2-treated as compared to AFB1-treated rats..."}
{"id": "PMID:187332", "title": "Mechanism of action of 2-amino-1,3,4-thiadiazole (NSC 4728).", "content": "The synthesis and isolation of two derivatives of 2-amino-1,3,4-thialdiazole(aminothiadiazole) are described. The derivatives are a nicotinamide adenine dinucleotide (NAD) analog prepared by an exchange reaction with NAD in the presence of nicotineamide adenine dinucleotide glycohydrolase and a presumed aminothiadiazole mononucleotide prepared by treatment of the NAD analog with nucleotide pyrophosphatase. Both derivatives are potent inhibitors of inosine 5'-phosphate (IMP) dehydrogenase obtained from leukemia L1210 cells. The NAD analog is a pseudoir-reversible inhibitor of the enzyme, noncompetitive with either IMP or NAD. The aminothiadiazole mononucleotide has a K1 of about 0.1 muM, is competitive with IMP, and is uncompetitive with NAD: the inhibition appears to be reversible by Ackermann-Potter analysis. A metabolite of [5-14C]aminothiadiazole is formed in L1210 cells in vivo to a level of 0.3 nmole/10(9) cells. Retention volume of the metabolite on a high-pressure liquid chromatography system is the same as that of the aminothiadiazole mononucleotide prepared as described above. These results suggest that IMP dehydrogenase is the site of action for aminothiadiazole metabolites as was indicated by earlier observations. There is no evidence that the NAD analog is formed in vivo. Nicotinamide prevented formation of the mononucleotide in vivo. Therefore, since formation and cleavage of the NAD analog apparently are not the route to the thiadiazole nucleotide, some other pathway for the metabolism of nicotinamide may be involved such as the action of a phosphoribosyltransferase or the sequential action of a nucleoside phosphorylase and a nucleoside kinase.", "contents": "Mechanism of action of 2-amino-1,3,4-thiadiazole (NSC 4728). The synthesis and isolation of two derivatives of 2-amino-1,3,4-thialdiazole(aminothiadiazole) are described. The derivatives are a nicotinamide adenine dinucleotide (NAD) analog prepared by an exchange reaction with NAD in the presence of nicotineamide adenine dinucleotide glycohydrolase and a presumed aminothiadiazole mononucleotide prepared by treatment of the NAD analog with nucleotide pyrophosphatase. Both derivatives are potent inhibitors of inosine 5'-phosphate (IMP) dehydrogenase obtained from leukemia L1210 cells. The NAD analog is a pseudoir-reversible inhibitor of the enzyme, noncompetitive with either IMP or NAD. The aminothiadiazole mononucleotide has a K1 of about 0.1 muM, is competitive with IMP, and is uncompetitive with NAD: the inhibition appears to be reversible by Ackermann-Potter analysis. A metabolite of [5-14C]aminothiadiazole is formed in L1210 cells in vivo to a level of 0.3 nmole/10(9) cells. Retention volume of the metabolite on a high-pressure liquid chromatography system is the same as that of the aminothiadiazole mononucleotide prepared as described above. These results suggest that IMP dehydrogenase is the site of action for aminothiadiazole metabolites as was indicated by earlier observations. There is no evidence that the NAD analog is formed in vivo. Nicotinamide prevented formation of the mononucleotide in vivo. Therefore, since formation and cleavage of the NAD analog apparently are not the route to the thiadiazole nucleotide, some other pathway for the metabolism of nicotinamide may be involved such as the action of a phosphoribosyltransferase or the sequential action of a nucleoside phosphorylase and a nucleoside kinase."}
{"id": "PMID:187333", "title": "Deficiency of S-adenosylmethionine-homocysteine methyltransferase activity in hepatoma cells.", "content": "S-Adenosylmethionine-homocysteine methyltransferase, which catalyzes synthesis of methionine from homocysteine, with the use of S-adenosylmethionine as the methyl donor, is absent in tumor tissue such as rat ascites hepatoma and Morris hepatoma but is present in rat liver homogenate. Absence of the enzymatic activity in tumor cells is not due to the action of an inhibitor. S-Adenosylhomocysteine hydrolase, however, is present in both rat liver and hepatoma tissue.", "contents": "Deficiency of S-adenosylmethionine-homocysteine methyltransferase activity in hepatoma cells. S-Adenosylmethionine-homocysteine methyltransferase, which catalyzes synthesis of methionine from homocysteine, with the use of S-adenosylmethionine as the methyl donor, is absent in tumor tissue such as rat ascites hepatoma and Morris hepatoma but is present in rat liver homogenate. Absence of the enzymatic activity in tumor cells is not due to the action of an inhibitor. S-Adenosylhomocysteine hydrolase, however, is present in both rat liver and hepatoma tissue."}
{"id": "PMID:187334", "title": "The effect of lymphoma and other neoplasms on hepatic and plasma enzymes of the host rat.", "content": "Considerable thymidine kinase and pyrroline-5-carboxylate reductase activities were found in the plasma of rats bearing a transplanted lymphoma; neither activity was detected in plasma of hosts carrying hepatic, renal, mammary, or submaxillary gland tumors. All host livers exhibited signs of biochemical immaturity as indicated by the appropriate increases or decreases in the concentrations of the nine enzymes measured. The extent and time schedule of the changes in host liver varied with the enzyme and with the tumor that caused them. The hepatic concentrations of ornithine aminotransferase, arginase, pyrroline-5-carboxylate reductase, and glucokinase (all diminished), and of peptidyl proline hydroxylase and hexokinase (increased) were sensitive indicators of tumor growth in general. The concentration of ornithine aminotransferase decreased before the tumors became palpable. At more advanced stages, the high hepatic thymidine kinase activity distinguished the presence of hepatoma and lymphoma from those of all other equally fast-growing tumors. However, only in lymphoma-bearing rats did a fivefold elevation of hepatic thymidine kinase occur as early as 4 days after implantation. Additional observations on the lymphoma itself, on blood cells, and on the involuting thymus of normal rats indicate that the striking systemic effects of this tumor cannot be explained by a release of enzymes from the thymus or by the increased number of lymphoma cells present in blood or liver.", "contents": "The effect of lymphoma and other neoplasms on hepatic and plasma enzymes of the host rat. Considerable thymidine kinase and pyrroline-5-carboxylate reductase activities were found in the plasma of rats bearing a transplanted lymphoma; neither activity was detected in plasma of hosts carrying hepatic, renal, mammary, or submaxillary gland tumors. All host livers exhibited signs of biochemical immaturity as indicated by the appropriate increases or decreases in the concentrations of the nine enzymes measured. The extent and time schedule of the changes in host liver varied with the enzyme and with the tumor that caused them. The hepatic concentrations of ornithine aminotransferase, arginase, pyrroline-5-carboxylate reductase, and glucokinase (all diminished), and of peptidyl proline hydroxylase and hexokinase (increased) were sensitive indicators of tumor growth in general. The concentration of ornithine aminotransferase decreased before the tumors became palpable. At more advanced stages, the high hepatic thymidine kinase activity distinguished the presence of hepatoma and lymphoma from those of all other equally fast-growing tumors. However, only in lymphoma-bearing rats did a fivefold elevation of hepatic thymidine kinase occur as early as 4 days after implantation. Additional observations on the lymphoma itself, on blood cells, and on the involuting thymus of normal rats indicate that the striking systemic effects of this tumor cannot be explained by a release of enzymes from the thymus or by the increased number of lymphoma cells present in blood or liver."}
{"id": "PMID:187335", "title": "Composition, associated tissue methyltransferase activity, and catabolic end products of transfer RNA from carcinogen-induced hepatoma and normal monkey livers.", "content": "This investigation was designed to explore transfer RNA (TRNA) methyltransferase activity, urinary excretion levels of tRNA degradation products, and tRNA base composition in normal monkeys and in those with hepatocellular carcinomas induced by N-nitrosodiethylamine. After the development of the tumor, 24-hr urine specimens were collected, the monkeys were sacrificed, and the livers were removed for tRNA isolation and methyltransferase activity studies. The tRNA methyltransferase activity and capacity and the urinary excretion levels for selected tRNA degradation products (pseudouridine, N2,N2-dimethylguanosine, 1-methylinosine, 7-methylguanine, and beta-aminoisobutyric acid) were elevated for the hepatoma-bearing monkeys when compared to those with normal liver. The isolated tRNA pools were analyzed by high-resolution liquid chromatography, and similar base compositions were found for the hepatoma-bearing and normal monkeys. With the use of methyl-deficient Escherichia coli tRNA as the methyl receptor and the analytical procedure for tRNA anlysis, the methylating ability of the tRNA methyltransferases in hepatoma and normal liver extracts was determined. The hepatoma methyltransferase homogenates were found to produce increased levels of 7-methylguanine, N2,N2-dimethylguanine, and thymine, while the normal liver extracts gave higher levels of N2-methylguanine. These differences were not apparent in the base composition of the tRNA pools. The increased urinary excretion and higher methyltransferase activity of the hepatoma-bearing monkeys without an apparent increase in the methylated base content of their tRNA suggest increased tRNA tf individual isoaccepting tRNA's would be missed by analyzing the tRNA pools. The variations in the individual tRNA methyltransferase activities of the hepatoma and normal liver homogenates indicate a difference in the methlation of their tRNA's.", "contents": "Composition, associated tissue methyltransferase activity, and catabolic end products of transfer RNA from carcinogen-induced hepatoma and normal monkey livers. This investigation was designed to explore transfer RNA (TRNA) methyltransferase activity, urinary excretion levels of tRNA degradation products, and tRNA base composition in normal monkeys and in those with hepatocellular carcinomas induced by N-nitrosodiethylamine. After the development of the tumor, 24-hr urine specimens were collected, the monkeys were sacrificed, and the livers were removed for tRNA isolation and methyltransferase activity studies. The tRNA methyltransferase activity and capacity and the urinary excretion levels for selected tRNA degradation products (pseudouridine, N2,N2-dimethylguanosine, 1-methylinosine, 7-methylguanine, and beta-aminoisobutyric acid) were elevated for the hepatoma-bearing monkeys when compared to those with normal liver. The isolated tRNA pools were analyzed by high-resolution liquid chromatography, and similar base compositions were found for the hepatoma-bearing and normal monkeys. With the use of methyl-deficient Escherichia coli tRNA as the methyl receptor and the analytical procedure for tRNA anlysis, the methylating ability of the tRNA methyltransferases in hepatoma and normal liver extracts was determined. The hepatoma methyltransferase homogenates were found to produce increased levels of 7-methylguanine, N2,N2-dimethylguanine, and thymine, while the normal liver extracts gave higher levels of N2-methylguanine. These differences were not apparent in the base composition of the tRNA pools. The increased urinary excretion and higher methyltransferase activity of the hepatoma-bearing monkeys without an apparent increase in the methylated base content of their tRNA suggest increased tRNA tf individual isoaccepting tRNA's would be missed by analyzing the tRNA pools. The variations in the individual tRNA methyltransferase activities of the hepatoma and normal liver homogenates indicate a difference in the methlation of their tRNA's."}
{"id": "PMID:187336", "title": "Inhibition of Herpesvirus saimiri replication by phosphonoacetic acid, benzo(a)pyrene, and methylcholanthrene.", "content": "The present investigations were undertaken to determine the possible effects of two carcinogenic polycyclic aromatic hydrocarbons, benzo(a)pyrene and 3-methylcholanthrene on Herpesvirus saimiri replication. The results from these experiments were compared with the effects of phosphonoacetic acid on the virus replication cycle. Phosphonoacetic acid inhibited the synthesis of virus-induced intracellular late antigens, membrane antigens and infectious virus but not the synthesis of the early antigens induced by H. saimiri. In contrast, benzo(a)pyrene and 3-methylcholanthrene inhibited primarily membrane antigen expression and infectious virus production. Benzo(a)pyrene was the most effective of the two compounds, with significant inhibition occurring with 2 mug/ml, whereas a minimum concentration of 10 mug/ml was required with 3-methylcholanthrene. Both compounds were most effective when present continuously during the 4-day infection process. However, exposure of infected cultures to a 3-hr pulse with each chemical also inhibited membrane antigen expression. Furthermore, pretreatment of cells for 48 hr before virus infection resulted in the inhibition of membrane antigen expression but not that of early or late antigens. These result demonstrate that some carcinogenic chemicals are capable of altering the H. saimiri replication cycle, primarily by inhibiting some but not all late events.", "contents": "Inhibition of Herpesvirus saimiri replication by phosphonoacetic acid, benzo(a)pyrene, and methylcholanthrene. The present investigations were undertaken to determine the possible effects of two carcinogenic polycyclic aromatic hydrocarbons, benzo(a)pyrene and 3-methylcholanthrene on Herpesvirus saimiri replication. The results from these experiments were compared with the effects of phosphonoacetic acid on the virus replication cycle. Phosphonoacetic acid inhibited the synthesis of virus-induced intracellular late antigens, membrane antigens and infectious virus but not the synthesis of the early antigens induced by H. saimiri. In contrast, benzo(a)pyrene and 3-methylcholanthrene inhibited primarily membrane antigen expression and infectious virus production. Benzo(a)pyrene was the most effective of the two compounds, with significant inhibition occurring with 2 mug/ml, whereas a minimum concentration of 10 mug/ml was required with 3-methylcholanthrene. Both compounds were most effective when present continuously during the 4-day infection process. However, exposure of infected cultures to a 3-hr pulse with each chemical also inhibited membrane antigen expression. Furthermore, pretreatment of cells for 48 hr before virus infection resulted in the inhibition of membrane antigen expression but not that of early or late antigens. These result demonstrate that some carcinogenic chemicals are capable of altering the H. saimiri replication cycle, primarily by inhibiting some but not all late events."}
{"id": "PMID:187337", "title": "Oncornavirus-induced sarcoma formation obscured by rapid development of lethal leukemia.", "content": "Injection i.v. of avian erythroblastosis virus (AEV) strain ES4 causes a high incidence of leukemia and the death of most of the inoculated chicks within 2 weeks. As found earlier, the virus is defective for replication and transforms bone marrow cultures in vitro, and surprisingly, also chick embryo fibroblasts. Inoculation of transformed AEV cells negative for virus production into newborn chicks induced the formation of sarcomas only, whereas cells superinfected with helper virus induced the formation of erythroblastosis in addition to sarcomas. The helper virus alone caused neither sarcomas nor erythroblastosis during the experimental period. These findings were explained by the hypothesis that AEV-induced erythroblastosis develops more rapidly than do AEV-induced sarcomas and that animals receiving i.v. injections die of the leukemia before sarcomas become detectable. The observation that animals receiving i.m. injections of AEV developed sarcomas at the site of injection strongly supports this concept. Most of the animals that received i.m. injections also developed an erythroblastosis that was delayed, however, in comparison to the animals receiving i.v. injections. Our data also suggest that the erythroblastosis induced by AEV does not suppress the formation of sarcomas in the same animal.", "contents": "Oncornavirus-induced sarcoma formation obscured by rapid development of lethal leukemia. Injection i.v. of avian erythroblastosis virus (AEV) strain ES4 causes a high incidence of leukemia and the death of most of the inoculated chicks within 2 weeks. As found earlier, the virus is defective for replication and transforms bone marrow cultures in vitro, and surprisingly, also chick embryo fibroblasts. Inoculation of transformed AEV cells negative for virus production into newborn chicks induced the formation of sarcomas only, whereas cells superinfected with helper virus induced the formation of erythroblastosis in addition to sarcomas. The helper virus alone caused neither sarcomas nor erythroblastosis during the experimental period. These findings were explained by the hypothesis that AEV-induced erythroblastosis develops more rapidly than do AEV-induced sarcomas and that animals receiving i.v. injections die of the leukemia before sarcomas become detectable. The observation that animals receiving i.m. injections of AEV developed sarcomas at the site of injection strongly supports this concept. Most of the animals that received i.m. injections also developed an erythroblastosis that was delayed, however, in comparison to the animals receiving i.v. injections. Our data also suggest that the erythroblastosis induced by AEV does not suppress the formation of sarcomas in the same animal."}
{"id": "PMID:187338", "title": "High inhibitory activity of a new antiestrogen, RU 16117 (11alpha-methoxy ethinyl estradiol), on the development of dimethylbenz(a)anthracene-induced mammary tumors.", "content": "From the first day of dimethylbenzanthracene administration, daily treatment with 8 or 24 mug of the new antiestrogen 11alpha-methoxy ethinyl estradiol (RU 16117) completely prevented the appearance of mammary tumors in all animals up to the last time interval studied (130 days after dimethyl benzanthracene administration). At daily doses of 0.5 and 2.0 mug RU 16117, the tumor incidence was reduced to 78.6 and 40%, respectively. Not only was the number of animals developing tumors reduced after injection of low doses of RU 16117, but the number of tumors per rat and the size of tumors were also markedly reduced. The levels of receptors for estradiol, progesterone, and prolactin in tumor tissue were reduced after treatment with 2.0 mug RU 16117, while the binding of growth hormone and insulin was not affected. Whereas plasma luteinizing hormone levels decreased after treatment with 8 or 24 mug RU 16117, plasma prolactin levels slightly increased in animals receiving the highest dose of the antiestrogen. It is thus likely that the potent inhibitory effect of RU 16117 on the development of dimethylbenzanthracene-induced mammary tumors results from actions at both the hypothalamic-pituitary and the tumor (mammary gland) levels, the action at the peripheral level possibly being secondary to a reduced sensitivity of the tissue to circulating hormones through lowering of hormone receptor concentrations.", "contents": "High inhibitory activity of a new antiestrogen, RU 16117 (11alpha-methoxy ethinyl estradiol), on the development of dimethylbenz(a)anthracene-induced mammary tumors. From the first day of dimethylbenzanthracene administration, daily treatment with 8 or 24 mug of the new antiestrogen 11alpha-methoxy ethinyl estradiol (RU 16117) completely prevented the appearance of mammary tumors in all animals up to the last time interval studied (130 days after dimethyl benzanthracene administration). At daily doses of 0.5 and 2.0 mug RU 16117, the tumor incidence was reduced to 78.6 and 40%, respectively. Not only was the number of animals developing tumors reduced after injection of low doses of RU 16117, but the number of tumors per rat and the size of tumors were also markedly reduced. The levels of receptors for estradiol, progesterone, and prolactin in tumor tissue were reduced after treatment with 2.0 mug RU 16117, while the binding of growth hormone and insulin was not affected. Whereas plasma luteinizing hormone levels decreased after treatment with 8 or 24 mug RU 16117, plasma prolactin levels slightly increased in animals receiving the highest dose of the antiestrogen. It is thus likely that the potent inhibitory effect of RU 16117 on the development of dimethylbenzanthracene-induced mammary tumors results from actions at both the hypothalamic-pituitary and the tumor (mammary gland) levels, the action at the peripheral level possibly being secondary to a reduced sensitivity of the tissue to circulating hormones through lowering of hormone receptor concentrations."}
{"id": "PMID:187341", "title": "Cell-cycle analysis of perturbed cell populations: computer simulation of sequential DNA distributions.", "content": "A mathematical model is presented that permits simulation of a time sequence of DNA distributions with a single set of cell-cycle parameters. The method is particularly suited to the quantitative analysis of sets of sequential DNA distributions from perturbed cell populations. The model permits determination of the durations and associated dispersions of the phases of the cell cycle as well as the point in the cell cycle at which the perturbing agent exerts its effect. The mathematical details of the simulation technique are presented, and the technique is applied to the analysis of DNA distributions from perturbed cell populations. Three cell populations are modeled: CHO-line cells released from a block at the interface of the G1-and S-phases, 3T3 cells released from a G1-phase block produced by serum starvation, and S49 mouse lymphoma cells responding to a block in the G1-phage produced by N6,02'-dibutyryl adenosine 3':5'-cyclic monophosphate (Bt2cAMP).", "contents": "Cell-cycle analysis of perturbed cell populations: computer simulation of sequential DNA distributions. A mathematical model is presented that permits simulation of a time sequence of DNA distributions with a single set of cell-cycle parameters. The method is particularly suited to the quantitative analysis of sets of sequential DNA distributions from perturbed cell populations. The model permits determination of the durations and associated dispersions of the phases of the cell cycle as well as the point in the cell cycle at which the perturbing agent exerts its effect. The mathematical details of the simulation technique are presented, and the technique is applied to the analysis of DNA distributions from perturbed cell populations. Three cell populations are modeled: CHO-line cells released from a block at the interface of the G1-and S-phases, 3T3 cells released from a G1-phase block produced by serum starvation, and S49 mouse lymphoma cells responding to a block in the G1-phage produced by N6,02'-dibutyryl adenosine 3':5'-cyclic monophosphate (Bt2cAMP)."}
{"id": "PMID:187342", "title": "The caudal neurosecretory system. A critical evaluation of the two-hormone hypothesis.", "content": "Recent information on the caudal neurosecretory system (urophysis) is collated, with special reference to cellular biology including neural relations, activity and chemistry 8 the biological principles associated with the urophysis, pharmacological analysis of the receptors for these principles, and their possible functions in a physiological sense. The existence of at least two principles, urotensins I and II, is well established. They differ pharmacologically and chemically and may arise from different cell types. At present, osmoregulation, cardiovascular regulation and reproduction are the most likely aspects of organismal physiology wherein these principles may be involved.", "contents": "The caudal neurosecretory system. A critical evaluation of the two-hormone hypothesis. Recent information on the caudal neurosecretory system (urophysis) is collated, with special reference to cellular biology including neural relations, activity and chemistry 8 the biological principles associated with the urophysis, pharmacological analysis of the receptors for these principles, and their possible functions in a physiological sense. The existence of at least two principles, urotensins I and II, is well established. They differ pharmacologically and chemically and may arise from different cell types. At present, osmoregulation, cardiovascular regulation and reproduction are the most likely aspects of organismal physiology wherein these principles may be involved."}
{"id": "PMID:187343", "title": "Localization of K+-stimulated p-NPPase in the lachrymal 'salt' gland of Malaclemys, using cytochemical and autoradiographical techniques.", "content": "Using two independent techniques, histochemistry and autoradiography, an enzyme (E.C. 3.6.1.3.) has been localized on basolateral cell membranes of salt secreting cells in the lachrymal gland of Malaclemys. This enzyme is ouabain sensitive. In addition an L-tetramisole sensitive alkaline phosphatase is found in the same sites, and an ethacrynic acid sensitive K+-stimulated p-NPPase is found on the apical membrane. The significance of these results with regard to the location of the pump responsible for net transepithelial sodium transport is discussed.", "contents": "Localization of K+-stimulated p-NPPase in the lachrymal 'salt' gland of Malaclemys, using cytochemical and autoradiographical techniques. Using two independent techniques, histochemistry and autoradiography, an enzyme (E.C. 3.6.1.3.) has been localized on basolateral cell membranes of salt secreting cells in the lachrymal gland of Malaclemys. This enzyme is ouabain sensitive. In addition an L-tetramisole sensitive alkaline phosphatase is found in the same sites, and an ethacrynic acid sensitive K+-stimulated p-NPPase is found on the apical membrane. The significance of these results with regard to the location of the pump responsible for net transepithelial sodium transport is discussed."}
{"id": "PMID:187344", "title": "Localization of ouabain-sensitive, potassium-dependent nitrophenyl phosphatase in the rectal gland of the spiny dogfish, Squalus acanthias.", "content": "Tissue from the digitiform rectal gland of the spiny dogfish, Squalus acanthias, was fixed briefly by formaldehyde perfusion and studied for the specificity and localization of p-nitrophenyl phosphatase (NPP'ase) activity. The enzymatic activity was K+-dependent (56%) and ouabain-sensitive (67%-inhibition). The electron-dense reaction product (SrPO4) of the cytochemical reaction (Ernst, 1972b) was localized along the inner surfaces of the basolateral membranes of the secretory cells. It was absent from mitochondria nuclei, vesicles, and other organelles. The luminal surface of the secretory cells was slightly reactive. On the basis of (1) this pattern of localization for the sodium transport system, (2) the presence of extensive intercellular labyrinthine channels (Bulger, 1963) that would facilitate \"standing gradients\" (Diamond and Bossert, 1968), and (3) the specific distribution of the energy-providing mitochondria, we conclude that the concentration and electrochemical gradients recorded from the secreting gland (Hayslett et al., 1974) are maintained across the domains of the basolateral surfaces of the secretory cells.", "contents": "Localization of ouabain-sensitive, potassium-dependent nitrophenyl phosphatase in the rectal gland of the spiny dogfish, Squalus acanthias. Tissue from the digitiform rectal gland of the spiny dogfish, Squalus acanthias, was fixed briefly by formaldehyde perfusion and studied for the specificity and localization of p-nitrophenyl phosphatase (NPP'ase) activity. The enzymatic activity was K+-dependent (56%) and ouabain-sensitive (67%-inhibition). The electron-dense reaction product (SrPO4) of the cytochemical reaction (Ernst, 1972b) was localized along the inner surfaces of the basolateral membranes of the secretory cells. It was absent from mitochondria nuclei, vesicles, and other organelles. The luminal surface of the secretory cells was slightly reactive. On the basis of (1) this pattern of localization for the sodium transport system, (2) the presence of extensive intercellular labyrinthine channels (Bulger, 1963) that would facilitate \"standing gradients\" (Diamond and Bossert, 1968), and (3) the specific distribution of the energy-providing mitochondria, we conclude that the concentration and electrochemical gradients recorded from the secreting gland (Hayslett et al., 1974) are maintained across the domains of the basolateral surfaces of the secretory cells."}
{"id": "PMID:187345", "title": "Estradiol-17 beta and cAMP: in vitro studies on the cervicovaginal epithelium of neonatal mice.", "content": "In organ culture of the cervicovaginal epithelium from neonatal mice, the epithelium synthesizes a material with specific antigenic properties (CVA). CVA was studied with immunofluorescence and the amount estimated semiquantitatively. In line with earlier studies, adenosine 3',5'-cyclic monophosphate (dibutyryl derivative (dcAMP), increased the amount of CVA, but adenosine 2',3'-cyclic monophosphate did not. Addition of histamine to the culture medium moderately increased the amount of CVA, whereas the anti-histamine diphenhydramine (H1-antagonist) slightly reduced the strong increase induced by dcAMP and estradiol in combination. No effect was seen under similar conditions using the H2-antagonist metiamide. Taken together with earlier results it is considered possible that the action of histamine and diphenhydramine is related to effects on the cell membranes. Phentolamine had no effect. The dcAMP effect was inhibited by actinomycin D and cycloheximide.", "contents": "Estradiol-17 beta and cAMP: in vitro studies on the cervicovaginal epithelium of neonatal mice. In organ culture of the cervicovaginal epithelium from neonatal mice, the epithelium synthesizes a material with specific antigenic properties (CVA). CVA was studied with immunofluorescence and the amount estimated semiquantitatively. In line with earlier studies, adenosine 3',5'-cyclic monophosphate (dibutyryl derivative (dcAMP), increased the amount of CVA, but adenosine 2',3'-cyclic monophosphate did not. Addition of histamine to the culture medium moderately increased the amount of CVA, whereas the anti-histamine diphenhydramine (H1-antagonist) slightly reduced the strong increase induced by dcAMP and estradiol in combination. No effect was seen under similar conditions using the H2-antagonist metiamide. Taken together with earlier results it is considered possible that the action of histamine and diphenhydramine is related to effects on the cell membranes. Phentolamine had no effect. The dcAMP effect was inhibited by actinomycin D and cycloheximide."}
{"id": "PMID:187346", "title": "Morphology and location of dense-core vesicles in the stomatogastric ganglion of the lobster, Panulirus interruptus.", "content": "The appearance and distribution of dense-core vesicles in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus, were examined using transmission electron microscopy. Following five fixation techniques, three types of dense-core vesicles were identified on the basis of size and morphology. Type-I vesicles are found in a distinct neuronal fiber system that appears to be involved in chemical transmission within the ganglion. Type-II vesicles occur in nerve processes in the ganglion, in major nerve trunks and in the perineural sheath of the nerves and ganglion. Type-III vesicles are present in all neuronal somata of the ganglion. The distinct morphology and location of the three types of vesicles suggest that their functional roles differ. Furthermore, the histochemical, biochemical and physiological data available for the stomatogastric ganglion indicate that Type-I vesicles may store dopamine.", "contents": "Morphology and location of dense-core vesicles in the stomatogastric ganglion of the lobster, Panulirus interruptus. The appearance and distribution of dense-core vesicles in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus, were examined using transmission electron microscopy. Following five fixation techniques, three types of dense-core vesicles were identified on the basis of size and morphology. Type-I vesicles are found in a distinct neuronal fiber system that appears to be involved in chemical transmission within the ganglion. Type-II vesicles occur in nerve processes in the ganglion, in major nerve trunks and in the perineural sheath of the nerves and ganglion. Type-III vesicles are present in all neuronal somata of the ganglion. The distinct morphology and location of the three types of vesicles suggest that their functional roles differ. Furthermore, the histochemical, biochemical and physiological data available for the stomatogastric ganglion indicate that Type-I vesicles may store dopamine."}
{"id": "PMID:187347", "title": "A cell type in sponges involved in the metabolism of glycogen. The gray cells.", "content": "The gray cells of four orders of demosponges contain basophilic inclusions and glycogen. They are capable of synthesis and accumulation of glycogen and responsible for its transfer to sites of more intense metabolism (growth, bud, blastema). They do not occur in larvae; but all the phases of their differentiation from the flagellar cells of the larva have been demonstrated.", "contents": "A cell type in sponges involved in the metabolism of glycogen. The gray cells. The gray cells of four orders of demosponges contain basophilic inclusions and glycogen. They are capable of synthesis and accumulation of glycogen and responsible for its transfer to sites of more intense metabolism (growth, bud, blastema). They do not occur in larvae; but all the phases of their differentiation from the flagellar cells of the larva have been demonstrated."}
{"id": "PMID:187350", "title": "Fluorescence studies on the interaction of the tumor promoter phorbol myristate acetate and related compounds with rat liver plasma membranes.", "content": "The interaction of the potent tumor-promoting agent phorbol myristate acetate (PMA) with purified rat liver plasma membranes suspended in phosphate-buffered saline (PBS), pH 7.4, was studied by fluorescence spectrophotometry. Exposure of membranes to PMA caused up to 21% decrease of the native membrane emission, i.e. the fluorescence of both tryptophan and tyrosine, compared to non-treated membranes. The decrease in the membrane emission varied with both the PMA and the membrane concentration. Treatment of rat liver plasma membranes with biologically less active analogs of PMA, phorbolol myristate acetate (PHMA) and 4a alpha-phorbol didecanoate (4a alpha-PDD), resulted in a 5-10% decrease of the native membrane emission. These studies suggest that PMA causes alterations in membrane structure which are due, at least in part, to conformational changes in the membrane proteins.", "contents": "Fluorescence studies on the interaction of the tumor promoter phorbol myristate acetate and related compounds with rat liver plasma membranes. The interaction of the potent tumor-promoting agent phorbol myristate acetate (PMA) with purified rat liver plasma membranes suspended in phosphate-buffered saline (PBS), pH 7.4, was studied by fluorescence spectrophotometry. Exposure of membranes to PMA caused up to 21% decrease of the native membrane emission, i.e. the fluorescence of both tryptophan and tyrosine, compared to non-treated membranes. The decrease in the membrane emission varied with both the PMA and the membrane concentration. Treatment of rat liver plasma membranes with biologically less active analogs of PMA, phorbolol myristate acetate (PHMA) and 4a alpha-phorbol didecanoate (4a alpha-PDD), resulted in a 5-10% decrease of the native membrane emission. These studies suggest that PMA causes alterations in membrane structure which are due, at least in part, to conformational changes in the membrane proteins."}
{"id": "PMID:187351", "title": "Effect of a single treatment with the alkylating carcinogens dimethylnitrosamine and methyl methanesulphonate on liver regenerating after partial hepatectomy. III. Effect on DNA synthesis in vivo and on DNA polymerase activity assayed in vitro.", "content": "A single treatment with dimethylnitrosamine (DMN) but not with methyl methanesulphonate (MMS) induces liver cell carcinoma if given during the period of restorative hyperplasia following partial hepatectomy, a higher incidence of tumours being induced if the carcinogen is given during the period of DNA synthesis (24 h after the operation) than if given early in the prereplicative stage (at 6 h). To study the effect of treatment with DMN and with MMS on the regenerating liver, DNA replication was measured in vivo in partially hepatectomised animals treated with the methylating agents, and DNA polymerase activity was assayed in vitro.", "contents": "Effect of a single treatment with the alkylating carcinogens dimethylnitrosamine and methyl methanesulphonate on liver regenerating after partial hepatectomy. III. Effect on DNA synthesis in vivo and on DNA polymerase activity assayed in vitro. A single treatment with dimethylnitrosamine (DMN) but not with methyl methanesulphonate (MMS) induces liver cell carcinoma if given during the period of restorative hyperplasia following partial hepatectomy, a higher incidence of tumours being induced if the carcinogen is given during the period of DNA synthesis (24 h after the operation) than if given early in the prereplicative stage (at 6 h). To study the effect of treatment with DMN and with MMS on the regenerating liver, DNA replication was measured in vivo in partially hepatectomised animals treated with the methylating agents, and DNA polymerase activity was assayed in vitro."}
{"id": "PMID:187352", "title": "Modifications of drug metabolism by disulfiram and diethyldithiocarbamate. I. Mixed-function oxygenase.", "content": "Disulfiram and diethyldithiocarbamate were administered to rats for 4 days alone (300 mg/kg, daily, per os) or in combination with phenobarbital (80 mg/kg, daily, i.p.), in order to observe the effects of these compounds on the microsomal membrane components and on the mixed-function oxygenase system. Both disulfiram and diethyldithiocarbamate increased the liver to body weight ratio, and the total hepatic protein content. Disulfiram significantly increased also the microsomal protein and phospholipid contents. Diethyldithiocarbamate and disulfiram partially prevented the increase of microsomal protein and phospholipid contents caused by phenobarbital. Disulfiram and diethyldithiocarbamate decreased the amount of cytochrome P-450 and P-420, and the activity of p-nitroanisole O-demethylase. These changes were more pronounced after diethyldithiocarbamate than after disulfiram treatment. On the contrary, the activity of NADPH-cytochrome c reductase was enhanced only by disulfiram. The induction by phenobarbital of cytochrome P-450 and p-nitrosanisole O-demethylase was partially prevented on concomitant treatment with disulfiram and diethyldithiocarbamate. These compounds. however, had an additive effect with phenobarbital in enhancing the microsomal NADPH-cytochrome c reductase activity.", "contents": "Modifications of drug metabolism by disulfiram and diethyldithiocarbamate. I. Mixed-function oxygenase. Disulfiram and diethyldithiocarbamate were administered to rats for 4 days alone (300 mg/kg, daily, per os) or in combination with phenobarbital (80 mg/kg, daily, i.p.), in order to observe the effects of these compounds on the microsomal membrane components and on the mixed-function oxygenase system. Both disulfiram and diethyldithiocarbamate increased the liver to body weight ratio, and the total hepatic protein content. Disulfiram significantly increased also the microsomal protein and phospholipid contents. Diethyldithiocarbamate and disulfiram partially prevented the increase of microsomal protein and phospholipid contents caused by phenobarbital. Disulfiram and diethyldithiocarbamate decreased the amount of cytochrome P-450 and P-420, and the activity of p-nitroanisole O-demethylase. These changes were more pronounced after diethyldithiocarbamate than after disulfiram treatment. On the contrary, the activity of NADPH-cytochrome c reductase was enhanced only by disulfiram. The induction by phenobarbital of cytochrome P-450 and p-nitrosanisole O-demethylase was partially prevented on concomitant treatment with disulfiram and diethyldithiocarbamate. These compounds. however, had an additive effect with phenobarbital in enhancing the microsomal NADPH-cytochrome c reductase activity."}
{"id": "PMID:187353", "title": "Modifications of drug metabolism by disulfiram and diethyldithiocarbamate. II. D-Glucuronic acid pathway.", "content": "Hepatic enzymes connected with the formation and metabolism of free D-glucuronic acid were affected in rats after treatment with disulfiram or diethyldithiocarbamate (300 mg/kg, intragastrically, per day, 4 X). The activities of UDPglucose dehydrogenase, UDPglucuronic acid pyrophosphatase, UDPglucuronosyltransferase and L-gulonate dehydrogenase were enhanced, while those of glucose-6-phosphate dehydrogenase, beta-glucuronidase and D-glucuronolactone dehydrogenase were inhibited. These changes were more pronounced with disulfiram than diethyldithiocarbamate. Treatment with phenobarbital (80 mg/kg, i.p., per day, 4 X) enhanced UDP glucuronosyl-transferase, but brought about different effects on the other enzymes. Concurrent administration of phenobarbital with disulfiram or diethyldithiocarbamate led to potentiation or antagonism of the primary effects of each compound when given alone. The results suggest that activation of the D-glucuronic acid pathway may proceed in various ways, and that it is not necessarily followed by a simultaneous induction of the microsomal mixed-function oxygenase activity.", "contents": "Modifications of drug metabolism by disulfiram and diethyldithiocarbamate. II. D-Glucuronic acid pathway. Hepatic enzymes connected with the formation and metabolism of free D-glucuronic acid were affected in rats after treatment with disulfiram or diethyldithiocarbamate (300 mg/kg, intragastrically, per day, 4 X). The activities of UDPglucose dehydrogenase, UDPglucuronic acid pyrophosphatase, UDPglucuronosyltransferase and L-gulonate dehydrogenase were enhanced, while those of glucose-6-phosphate dehydrogenase, beta-glucuronidase and D-glucuronolactone dehydrogenase were inhibited. These changes were more pronounced with disulfiram than diethyldithiocarbamate. Treatment with phenobarbital (80 mg/kg, i.p., per day, 4 X) enhanced UDP glucuronosyl-transferase, but brought about different effects on the other enzymes. Concurrent administration of phenobarbital with disulfiram or diethyldithiocarbamate led to potentiation or antagonism of the primary effects of each compound when given alone. The results suggest that activation of the D-glucuronic acid pathway may proceed in various ways, and that it is not necessarily followed by a simultaneous induction of the microsomal mixed-function oxygenase activity."}
{"id": "PMID:187354", "title": "[Evidence for existence of pores in intramembranous particles revealed by freeze fracturing].", "content": "In freeze-fracture replicas of membranes (plasma and intracellular) in a variety of animal cells, it is possible to detect the presence of intramembrane particles containing an electron-dense spot. The spot is interpreted as an accumulation of platinum into a cavity; the cavity could in turn correspond to a hydrophilic pore in the particle.", "contents": "[Evidence for existence of pores in intramembranous particles revealed by freeze fracturing]. In freeze-fracture replicas of membranes (plasma and intracellular) in a variety of animal cells, it is possible to detect the presence of intramembrane particles containing an electron-dense spot. The spot is interpreted as an accumulation of platinum into a cavity; the cavity could in turn correspond to a hydrophilic pore in the particle."}
{"id": "PMID:187355", "title": "[Glycogen phosphorylase activity of full term immature human placentas].", "content": "Human placenta contains glycogen phosphorylase activity (E.C. 2.4.1.1) in two interconvertible forms, one is already active and the other is actibatable by 5' AMP. The human placenta contains also a sufficient amount of endogenous phosphorylase b kinase and phosphorylase a phosphatase, to allow this interconversion. The phosphorylase activity is higher in immature placentas than in full-term organs, as in the latter the inactive phosphorylase is only partially revealed by 5' AMP as in other steroidogenic organs. By contrast, in immature placentas the inactive glycogen phosphorylase is completely revealed by this nucleotide.", "contents": "[Glycogen phosphorylase activity of full term immature human placentas]. Human placenta contains glycogen phosphorylase activity (E.C. 2.4.1.1) in two interconvertible forms, one is already active and the other is actibatable by 5' AMP. The human placenta contains also a sufficient amount of endogenous phosphorylase b kinase and phosphorylase a phosphatase, to allow this interconversion. The phosphorylase activity is higher in immature placentas than in full-term organs, as in the latter the inactive phosphorylase is only partially revealed by 5' AMP as in other steroidogenic organs. By contrast, in immature placentas the inactive glycogen phosphorylase is completely revealed by this nucleotide."}
{"id": "PMID:187356", "title": "[Suppression of paradoxal sleep by clonidine in man].", "content": "The administration of clonidine (300 mug) suppresses REM sleep or strikingly diminishes its duration in Man. The statistical difference with placebo given in a double blind trial is highly significant. This suppression of REM sleep may depend on the stimulation of alpha-adrenergic receptors.", "contents": "[Suppression of paradoxal sleep by clonidine in man]. The administration of clonidine (300 mug) suppresses REM sleep or strikingly diminishes its duration in Man. The statistical difference with placebo given in a double blind trial is highly significant. This suppression of REM sleep may depend on the stimulation of alpha-adrenergic receptors."}
{"id": "PMID:187357", "title": "[Effect of N-6 2'-O-dibutyryl adenosine 3'-5'monophosphate (dibutyryl cyclic AMP) on the condenstion of the X chromosome into the form of a Barr body].", "content": "Addition of exogen DB-c AMP in medium of human fibroblasts culture, with 46 XX karyotypes, enables us to observe a high frequency of Barr bodies, about 80 or 85%. This observation suggests that the condensation of the X chromosome in the form of Barr bodies depends on the level of endogen cyclic AMP.", "contents": "[Effect of N-6 2'-O-dibutyryl adenosine 3'-5'monophosphate (dibutyryl cyclic AMP) on the condenstion of the X chromosome into the form of a Barr body]. Addition of exogen DB-c AMP in medium of human fibroblasts culture, with 46 XX karyotypes, enables us to observe a high frequency of Barr bodies, about 80 or 85%. This observation suggests that the condensation of the X chromosome in the form of Barr bodies depends on the level of endogen cyclic AMP."}
{"id": "PMID:187358", "title": "Quantification of apolipoprotein B in grossly normal human aorta.", "content": "A quantitiative electroimmunodiffusion (EID) assay was developed for apolipoprotein B (apoB), the major apoprotein of human plasma low density lipoproteins (LDL) and very low density lipoproteins (VLDL). Specificity, sensitivity (30-200 ng) and reproducibility (11%) were established. We used this system to determine the amount of buffer-soluble apoB in supernatant fractions from homogenates of the intima from grossly normal human aortas. Assays of whole tissue minces yielded only one-third of the apoB in supernatant fractions. Intimal homogenates contained 0.34-18.45 mug of apoB/mg of tissue, dry weight (mean 5.42 +/- 3.95 SD). We also found that no apoB was detected in the homogenates of adjacent tunica media. Furthermore, most of the intimal apoB was found in the LDL density (d) fraction (d 1.006-1.063) after differential ultracentrifugation, while the VLDL (d less than 1.006) fraction contained only negligible amounts of apoB. By electron microscopy, it was determined that the LDL density fraction contained particles 200-250 A in diameter which were similar in size to plasma LDL. These results suggest that grossly normal aortas contain significant quantities of intact LDL.", "contents": "Quantification of apolipoprotein B in grossly normal human aorta. A quantitiative electroimmunodiffusion (EID) assay was developed for apolipoprotein B (apoB), the major apoprotein of human plasma low density lipoproteins (LDL) and very low density lipoproteins (VLDL). Specificity, sensitivity (30-200 ng) and reproducibility (11%) were established. We used this system to determine the amount of buffer-soluble apoB in supernatant fractions from homogenates of the intima from grossly normal human aortas. Assays of whole tissue minces yielded only one-third of the apoB in supernatant fractions. Intimal homogenates contained 0.34-18.45 mug of apoB/mg of tissue, dry weight (mean 5.42 +/- 3.95 SD). We also found that no apoB was detected in the homogenates of adjacent tunica media. Furthermore, most of the intimal apoB was found in the LDL density (d) fraction (d 1.006-1.063) after differential ultracentrifugation, while the VLDL (d less than 1.006) fraction contained only negligible amounts of apoB. By electron microscopy, it was determined that the LDL density fraction contained particles 200-250 A in diameter which were similar in size to plasma LDL. These results suggest that grossly normal aortas contain significant quantities of intact LDL."}
{"id": "PMID:187359", "title": "Chronic labile hypertension produced by lesions of the nucleus tractus solitarii in the cat.", "content": "Bilateral electrolytic lesions of the nucleus tractus solitarii (NTS) were made at the level of the obex in seven cats. Within 1 hour the mean arterial pressure (MAP) rose to a maximum of 144 mm Hg (141% of control), and by 7 hours heart rate reached a peak of 236 beats/min (148% of control). The baroreceptor reflexes were abolished. After 24 hours the arterial pressure became extremely labile, with variations of 80-100 mm Hg observed. The lability occurred spontaneously and during behaviors that were self-initiated or elicited by environmental stimuli. The MAP in the lesion group was 144 mm Hg (180% of control) during the day, and 96 mm Hg (120% of control) at night. The lability, measured by the standard deviation, during the day in the lesion group was 4 times greater than in the control group and at night there were no differences. The heart rate of the lesion group was always higher than that of the control group but the lability of both groups was the same. We conclude that lesions of the NTS produced labile hypertension, probably by disinhibition of sympathetic activity through central interruption of the baroreceptor reflexes. The higher, more labile arterial pressures during the day may be caused by uninhibited increases in sympathetic activity elicited by environmental stimuli that are present during the day and absent at night. The daily variation of pressure may also be caused by somatomotor activity or by a daily rhythm of sympathetic activity which is unmasked by the lesions.", "contents": "Chronic labile hypertension produced by lesions of the nucleus tractus solitarii in the cat. Bilateral electrolytic lesions of the nucleus tractus solitarii (NTS) were made at the level of the obex in seven cats. Within 1 hour the mean arterial pressure (MAP) rose to a maximum of 144 mm Hg (141% of control), and by 7 hours heart rate reached a peak of 236 beats/min (148% of control). The baroreceptor reflexes were abolished. After 24 hours the arterial pressure became extremely labile, with variations of 80-100 mm Hg observed. The lability occurred spontaneously and during behaviors that were self-initiated or elicited by environmental stimuli. The MAP in the lesion group was 144 mm Hg (180% of control) during the day, and 96 mm Hg (120% of control) at night. The lability, measured by the standard deviation, during the day in the lesion group was 4 times greater than in the control group and at night there were no differences. The heart rate of the lesion group was always higher than that of the control group but the lability of both groups was the same. We conclude that lesions of the NTS produced labile hypertension, probably by disinhibition of sympathetic activity through central interruption of the baroreceptor reflexes. The higher, more labile arterial pressures during the day may be caused by uninhibited increases in sympathetic activity elicited by environmental stimuli that are present during the day and absent at night. The daily variation of pressure may also be caused by somatomotor activity or by a daily rhythm of sympathetic activity which is unmasked by the lesions."}
{"id": "PMID:187360", "title": "Simplified method for determination of protocollagen proline hydroxylase.", "content": "Preparation of (14C) Pro labeled protocollagen and requirements for its hydroxylation by PPH was investigated. Protocollagen can be prepared by centrifugation of the biological material at 15.000 X g. Substances in current use, viz catalase, bovine serum albumin and dithiothreitol were found unnecessary under the hydroxylation conditions used. A decrease in PPH in the testis and skin of rats with increasing age was demonstrated.", "contents": "Simplified method for determination of protocollagen proline hydroxylase. Preparation of (14C) Pro labeled protocollagen and requirements for its hydroxylation by PPH was investigated. Protocollagen can be prepared by centrifugation of the biological material at 15.000 X g. Substances in current use, viz catalase, bovine serum albumin and dithiothreitol were found unnecessary under the hydroxylation conditions used. A decrease in PPH in the testis and skin of rats with increasing age was demonstrated."}
{"id": "PMID:187361", "title": "Evaluation of a simple cortisol assay by competitive protein binding technique.", "content": "The evaluation of a recently introduced kit (Cortipac (R)) for measuring plasma cortisol by competitive protein binding technique without prior extraction of steroids from plasma, is presented. The blank value was less than 2.5 mug/100 ml, and the lowest measurable value was 2.5 mug/100 ml. The coefficients of variation within- and between-batch determinations were 8.64% and 9.21% respectively. By adding known amounts of cortisol to pre-extracted plasma a linear correlation between calculated and measured cortisol was obtained. In comparison with the double isotope derivate technique, a linear correlation was found. A high degree of cross-reaction was found with nearly all of 11 tested steroids. Due to the considerably higher plasma cortisol concentration in most clinical cond-tions, the lack of specificity may be of minor importance, but must be considered in evaluating increased plasma cortisol values. The mean plasma cortisol concentration in normal subjects (20.3 mug/100 ml) was equal to or slightly higher than found by other methods. The kit was found appropriate for routine clinical application, due to the easy, rapid and inespensive performance with an acceptable recovery and reliability, but it cannot entirely replace more specific methods.", "contents": "Evaluation of a simple cortisol assay by competitive protein binding technique. The evaluation of a recently introduced kit (Cortipac (R)) for measuring plasma cortisol by competitive protein binding technique without prior extraction of steroids from plasma, is presented. The blank value was less than 2.5 mug/100 ml, and the lowest measurable value was 2.5 mug/100 ml. The coefficients of variation within- and between-batch determinations were 8.64% and 9.21% respectively. By adding known amounts of cortisol to pre-extracted plasma a linear correlation between calculated and measured cortisol was obtained. In comparison with the double isotope derivate technique, a linear correlation was found. A high degree of cross-reaction was found with nearly all of 11 tested steroids. Due to the considerably higher plasma cortisol concentration in most clinical cond-tions, the lack of specificity may be of minor importance, but must be considered in evaluating increased plasma cortisol values. The mean plasma cortisol concentration in normal subjects (20.3 mug/100 ml) was equal to or slightly higher than found by other methods. The kit was found appropriate for routine clinical application, due to the easy, rapid and inespensive performance with an acceptable recovery and reliability, but it cannot entirely replace more specific methods."}
{"id": "PMID:187362", "title": "The use of NADH as a standard in a modified PMS-INT colorimetric assay of lactate dehydrogenase.", "content": "A new and more reliable way of quantitating lactate dehydrogenase activity, using NADH as a standard in a colorimetric assay, is proposed. Adopting the scheme, we obtained a CV of 2.6% and precision (95% limits) of +/-5.4% for enzyme activities ranging from 110 to 600 U/l. Comparative study against the modified kinetic method of Amador et al. showed excellent correlation, r = 0.99, p  less than 0.001. A normal range of 75 to 203 U/l was determined for the proposed scheme.", "contents": "The use of NADH as a standard in a modified PMS-INT colorimetric assay of lactate dehydrogenase. A new and more reliable way of quantitating lactate dehydrogenase activity, using NADH as a standard in a colorimetric assay, is proposed. Adopting the scheme, we obtained a CV of 2.6% and precision (95% limits) of +/-5.4% for enzyme activities ranging from 110 to 600 U/l. Comparative study against the modified kinetic method of Amador et al. showed excellent correlation, r = 0.99, p  less than 0.001. A normal range of 75 to 203 U/l was determined for the proposed scheme."}
{"id": "PMID:187366", "title": "Sclerosteosis - an autosomal recessive disorder.", "content": "Sclerosteosis is a rare, potentially lethal skeletal disorder in which massive bony over-growth leads to facial distortion, cranial nerve compression and progressive rise in intracranial pressure. Gigantism and syndactyly of the 2nd and 3rd fingers are associated features. In a nationwide investigation in South Africa, 25 affected individuals in 15 Afrikaner kindreds have been studied. The minimum prevalence of the contition in this community is 1 in 75,000. Analysis of pedigree data confirms that sclerosteosis is an autosomal recessive condition. The gene frequency in the Afrikaner people is estimated at 0.0035, with 10,000 clinically normal heterozygotes in this population. Heterozygote detection may be possible on a basis of recognition of minor changes which are apparent on skull radiographs.", "contents": "Sclerosteosis - an autosomal recessive disorder. Sclerosteosis is a rare, potentially lethal skeletal disorder in which massive bony over-growth leads to facial distortion, cranial nerve compression and progressive rise in intracranial pressure. Gigantism and syndactyly of the 2nd and 3rd fingers are associated features. In a nationwide investigation in South Africa, 25 affected individuals in 15 Afrikaner kindreds have been studied. The minimum prevalence of the contition in this community is 1 in 75,000. Analysis of pedigree data confirms that sclerosteosis is an autosomal recessive condition. The gene frequency in the Afrikaner people is estimated at 0.0035, with 10,000 clinically normal heterozygotes in this population. Heterozygote detection may be possible on a basis of recognition of minor changes which are apparent on skull radiographs."}
{"id": "PMID:187367", "title": "Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in F1 (BALB/c X NZB) hybrid mice derived by ovum transplantation.", "content": "F1(BALB/c X NZB)hybrid progeny derived by ovum transplantation were used to study the transmission of auto-immune haemolytic anaemia and murine leukaemia virus (MuLV) by male New Zealand black (NZB) mice. Fertilized ova, collected from the normal BALB/c partners 3 1/2 days after mating, were transferred to other, surrogate, BALB/c mothers, which then carried, delivered, and reared the hybrid young. This technical manoeuvre effectively closed the congenital transplacental route theoretically available to any infectious MuLV originating from the NZB father. Nevertheless, such progeny developed exactly the same profile of auto-immune haemolytic disease and the same range of diverse malignancies as their normally-derived F1(BALB/c X NZB) counterparts, and they carried type C MuLV particles readily detectable by electronmicroscopy. We concluded, therefore, that both the auto-immunity and virus were transmitted before placentation, presumably by the NZB male at fertilization, and probably as genetic information.", "contents": "Transmission of auto-immune haemolytic anaemia and murine leukaemia virus in F1 (BALB/c X NZB) hybrid mice derived by ovum transplantation. F1(BALB/c X NZB)hybrid progeny derived by ovum transplantation were used to study the transmission of auto-immune haemolytic anaemia and murine leukaemia virus (MuLV) by male New Zealand black (NZB) mice. Fertilized ova, collected from the normal BALB/c partners 3 1/2 days after mating, were transferred to other, surrogate, BALB/c mothers, which then carried, delivered, and reared the hybrid young. This technical manoeuvre effectively closed the congenital transplacental route theoretically available to any infectious MuLV originating from the NZB father. Nevertheless, such progeny developed exactly the same profile of auto-immune haemolytic disease and the same range of diverse malignancies as their normally-derived F1(BALB/c X NZB) counterparts, and they carried type C MuLV particles readily detectable by electronmicroscopy. We concluded, therefore, that both the auto-immunity and virus were transmitted before placentation, presumably by the NZB male at fertilization, and probably as genetic information."}
{"id": "PMID:187368", "title": "The xeroradiographic appearances of some uncommon malignant mammary neoplasms.", "content": "The clinical and xeroradiographic appearances are described of four patients with malignant lymphomatous involvement of the breast, two with breast involvement by acute leukaemia, and four with primary fibrosarcoma of the breast. In one patient with malignant lymhoma and multiple palpable masses, the radiological appearance resembled benign mammary dysplasia, but in the three other patients, one with a discrete clinical mass, and two with diffuse clinical involvement, radiological examination of the breast showed skin thickening with diffuse abnormalities of the trabecular pattern, most marked in the subdermal area. One of the patients with leukaemia had a discrete palpable mass and the other had diffuse clinical involvement, but the radiological appearances in both patients were similar and resembled those of a carcinoma. The clinical and radiological appearance of the patients with fibrosarcoma were those of a benign cyst or a fibroadenoma.", "contents": "The xeroradiographic appearances of some uncommon malignant mammary neoplasms. The clinical and xeroradiographic appearances are described of four patients with malignant lymphomatous involvement of the breast, two with breast involvement by acute leukaemia, and four with primary fibrosarcoma of the breast. In one patient with malignant lymhoma and multiple palpable masses, the radiological appearance resembled benign mammary dysplasia, but in the three other patients, one with a discrete clinical mass, and two with diffuse clinical involvement, radiological examination of the breast showed skin thickening with diffuse abnormalities of the trabecular pattern, most marked in the subdermal area. One of the patients with leukaemia had a discrete palpable mass and the other had diffuse clinical involvement, but the radiological appearances in both patients were similar and resembled those of a carcinoma. The clinical and radiological appearance of the patients with fibrosarcoma were those of a benign cyst or a fibroadenoma."}
{"id": "PMID:187370", "title": "The scintigraphic demonstration of acute myocardial infarcts.", "content": "The feasibility of acute infarct scintigraphy for the clinical evaluation of patients with known or suspected acute myocardial infarction is established. Further development of this methodologic approach may result in even better agents for the visualization of infarcts. Radiotracers with high affinity for the infarct, rapid blood clearance, and low concentrations in surrounding organs, such as liver and bone, would be more suitable than available radiopharmaceuticals for acute myocardial infarct scintigraphy. Ultimately, labeling these tracers and ultra-short-lived radionuclides will enable rapid sequential imaging to assess changes in the extent of infarction and to determine the efficacy of therapies aimed at limiting infarct size.", "contents": "The scintigraphic demonstration of acute myocardial infarcts. The feasibility of acute infarct scintigraphy for the clinical evaluation of patients with known or suspected acute myocardial infarction is established. Further development of this methodologic approach may result in even better agents for the visualization of infarcts. Radiotracers with high affinity for the infarct, rapid blood clearance, and low concentrations in surrounding organs, such as liver and bone, would be more suitable than available radiopharmaceuticals for acute myocardial infarct scintigraphy. Ultimately, labeling these tracers and ultra-short-lived radionuclides will enable rapid sequential imaging to assess changes in the extent of infarction and to determine the efficacy of therapies aimed at limiting infarct size."}
{"id": "PMID:187371", "title": "On a shoestring: a consumer-based source of personpower for mental health education.", "content": "This paper outlines a program for promoting mental health in the population by \"giving away our skills\" as mental health professionals. This kind of program can be started on a shoestring by a community mental health center, family service agency, or adult education program. It consists of teaching parent-child communication courses, with selected parents then becoming instructors to build a network of nonprofessional personpower. The paper explores strategies of setting up programs. It explores the shifting role of the professional toward a colleague relationship with nonprofessionals. Finally, it presents research on the program's effectiveness with parents and the impact on the lives and self-images of the nonprofessional instructors themselves.", "contents": "On a shoestring: a consumer-based source of personpower for mental health education. This paper outlines a program for promoting mental health in the population by \"giving away our skills\" as mental health professionals. This kind of program can be started on a shoestring by a community mental health center, family service agency, or adult education program. It consists of teaching parent-child communication courses, with selected parents then becoming instructors to build a network of nonprofessional personpower. The paper explores strategies of setting up programs. It explores the shifting role of the professional toward a colleague relationship with nonprofessionals. Finally, it presents research on the program's effectiveness with parents and the impact on the lives and self-images of the nonprofessional instructors themselves."}
{"id": "PMID:187372", "title": "Is NIMH's dream coming true? Wyoming centers reduce state hospital admissions.", "content": "Do comprehensive community mental health services reduce admissions to state hospital? A recent Nader report says no. Surprisingly few studies have documented the success of comprehensive community mental health programs. Wyoming had four unique characteristics that aided in evaluating the impact of centers on hospital admissions. The results of this study indicated that community-based comprehensive mental health  services do, in fact, reduce psychiatric hospitalization.", "contents": "Is NIMH's dream coming true? Wyoming centers reduce state hospital admissions. Do comprehensive community mental health services reduce admissions to state hospital? A recent Nader report says no. Surprisingly few studies have documented the success of comprehensive community mental health programs. Wyoming had four unique characteristics that aided in evaluating the impact of centers on hospital admissions. The results of this study indicated that community-based comprehensive mental health  services do, in fact, reduce psychiatric hospitalization."}
{"id": "PMID:187375", "title": "The action of arterial hypertension on lipid and lipoprotein metabolism. II. Qualitative and quantitative alterations of blood serum, liver and aortic lipids and lipoproteins in Okamoto-Aoki rats with spontaneous hypertension.", "content": "The purpose of the study was to investigate alterations in the content of the basic lipid fractions, and of the low density lipoproteins (LDL) in the liver, the blood serum and aorta, as well as to determine by acrylamide disc electrophoresis the hyperlipoproteinaemic type of spontaneously hypertensive rats (SHR) which are considered as the most suitable model of essential hypertension. The experiments were carried out on 25 normotensive control Wistar rats and 30 SHR (Okamoto-Aoki strain). An augmentation of lipid metabolism in the liver and a moderate hyperlipidaemia mainly due to an increase in triglycerides was found. The quantitative alterations of the lipid fractions corresponded with the qualitative alterations of the lipoproteins, an intensive and permanent pre-beta-LP fraction being established. In all the SHR a peculiar pattern of hyperlipoproteinaemia differing from the basic Fredickson-Lees patterns by a LP-fraction located between tha alpha- and beta-LP fractions was also established. The alterations in the lipid and lipoprotein metabolism in SHR are considered as connected with the hypertensive state itself since no accompanying atherosclerosis was observed.", "contents": "The action of arterial hypertension on lipid and lipoprotein metabolism. II. Qualitative and quantitative alterations of blood serum, liver and aortic lipids and lipoproteins in Okamoto-Aoki rats with spontaneous hypertension. The purpose of the study was to investigate alterations in the content of the basic lipid fractions, and of the low density lipoproteins (LDL) in the liver, the blood serum and aorta, as well as to determine by acrylamide disc electrophoresis the hyperlipoproteinaemic type of spontaneously hypertensive rats (SHR) which are considered as the most suitable model of essential hypertension. The experiments were carried out on 25 normotensive control Wistar rats and 30 SHR (Okamoto-Aoki strain). An augmentation of lipid metabolism in the liver and a moderate hyperlipidaemia mainly due to an increase in triglycerides was found. The quantitative alterations of the lipid fractions corresponded with the qualitative alterations of the lipoproteins, an intensive and permanent pre-beta-LP fraction being established. In all the SHR a peculiar pattern of hyperlipoproteinaemia differing from the basic Fredickson-Lees patterns by a LP-fraction located between tha alpha- and beta-LP fractions was also established. The alterations in the lipid and lipoprotein metabolism in SHR are considered as connected with the hypertensive state itself since no accompanying atherosclerosis was observed."}
{"id": "PMID:187376", "title": "Some aspects of rat kidney plasma membrane cAMP-receptor and its connection with protein kinase activity.", "content": "Rat kidney plasma membranes prepared by the method of FITZPATRICK et al. (J Biol. Chem. 244, 3561, 1969) show protein kinase activity as well as specific cAMP binding activity (diss. const. 1.3 x 10-9 M). However, no stimulation of kinase activity by cAMP is observed in presence of exogenous substrates (e.g. histone) and only poor stimulation with endogenous substrates in the membrane could be shown. At high ionic strength (1 M NaCl) cAMP independent protein kinase activity can be solubilized. Low ionic strength buffer (1 mM Tris-HCl pH 7.4 1 mM EDTA) and non-ionic detergents (Lubrol PX, Lubrol WX and Triton X 100) are able to solubilize both protein kinase activity and cAMP binding activity. Protein kinase activity seemed to be only loosely associated with the membrane, whereas cAMP binding protein appears to be more firmly fixed into the membrane structure. In addition we have found that membranes serve as a good substrate for cytosol protein kinase (s) and Ca-ion concentration influences the effect of cAMP on protein kinase activity. Dependent on the increase of Ca-ion concentration the effect of cAMP on protein kinase changes from activation to inhibition.", "contents": "Some aspects of rat kidney plasma membrane cAMP-receptor and its connection with protein kinase activity. Rat kidney plasma membranes prepared by the method of FITZPATRICK et al. (J Biol. Chem. 244, 3561, 1969) show protein kinase activity as well as specific cAMP binding activity (diss. const. 1.3 x 10-9 M). However, no stimulation of kinase activity by cAMP is observed in presence of exogenous substrates (e.g. histone) and only poor stimulation with endogenous substrates in the membrane could be shown. At high ionic strength (1 M NaCl) cAMP independent protein kinase activity can be solubilized. Low ionic strength buffer (1 mM Tris-HCl pH 7.4 1 mM EDTA) and non-ionic detergents (Lubrol PX, Lubrol WX and Triton X 100) are able to solubilize both protein kinase activity and cAMP binding activity. Protein kinase activity seemed to be only loosely associated with the membrane, whereas cAMP binding protein appears to be more firmly fixed into the membrane structure. In addition we have found that membranes serve as a good substrate for cytosol protein kinase (s) and Ca-ion concentration influences the effect of cAMP on protein kinase activity. Dependent on the increase of Ca-ion concentration the effect of cAMP on protein kinase changes from activation to inhibition."}
{"id": "PMID:187377", "title": "Effect of cyclic nucleotides on the isotonic fluid reabsorption in the proximal convoluted tubule of rat kidney.", "content": "In order to reveal the sidedness of the cyclic AMP action on renal tubules the effect of cyclic nucleotides on isotonic fluid reabsorption was examined in proximal convoluted rat kidney tubules by using advanced micropuncture techniques. Cyclic AMP inhibited isotonic fluid reabsorption preferentially when applied on the luminal cell side. This finding coincides with a predominant distribution of a membrane bound cyclic AMP dependent protein kinase in a luminal cell membrane fraction. On the luminal cell side cyclic AMP and dibutyryl cyclic AMP inhibited isotonic fluid reabsorption in a similar dose dependent behaviour. Concentrations of both nucleotides as low as 10-10M had a definite inhibitory effect. Tested at a high concentration N6-butyryl cyclic AMP was almost as effective as cyclic AMP. Deoxy cyclic AMP, 5' AMP, cyclic GMP and dibutyryl cyclic GMP had no effect. ATP inhibited isotonic fluid reabsorption to a very small extent. The data indicate that the observed inhibition of isotonic fluid reabsorption is specific for cyclic AMP and that the interaction of cyclic AMP and the luminal cell membrane is initiated at the luminal cell surface.", "contents": "Effect of cyclic nucleotides on the isotonic fluid reabsorption in the proximal convoluted tubule of rat kidney. In order to reveal the sidedness of the cyclic AMP action on renal tubules the effect of cyclic nucleotides on isotonic fluid reabsorption was examined in proximal convoluted rat kidney tubules by using advanced micropuncture techniques. Cyclic AMP inhibited isotonic fluid reabsorption preferentially when applied on the luminal cell side. This finding coincides with a predominant distribution of a membrane bound cyclic AMP dependent protein kinase in a luminal cell membrane fraction. On the luminal cell side cyclic AMP and dibutyryl cyclic AMP inhibited isotonic fluid reabsorption in a similar dose dependent behaviour. Concentrations of both nucleotides as low as 10-10M had a definite inhibitory effect. Tested at a high concentration N6-butyryl cyclic AMP was almost as effective as cyclic AMP. Deoxy cyclic AMP, 5' AMP, cyclic GMP and dibutyryl cyclic GMP had no effect. ATP inhibited isotonic fluid reabsorption to a very small extent. The data indicate that the observed inhibition of isotonic fluid reabsorption is specific for cyclic AMP and that the interaction of cyclic AMP and the luminal cell membrane is initiated at the luminal cell surface."}
{"id": "PMID:187379", "title": "Role of mitochondrial Ca2+ in antidiuretic hormone action.", "content": "The calcium ion concentration measured in rat kidney mitochondria, isolated from vasopressin treated tissue, has a dose response characteristic in which the calcium concentration reached a minimum at low doses of vasopressin (2 mU/ml), at higher doses of hormone the mitochondrial calcium ion concentration increases reaching a value close to that of the controls with vasopressin (100 mU/ml). This efflux and subsequent uptake of mitochondrial calcium has been shown to be a direct effect of the varying cyclic AMP concentrations. Sodium and water permeability effects of vasopressin have been shown in toad bladder to have different dose response characteristics. Maximum sodium transport occurs at a lower dose of vasopressin (2 mU/ml) and is believed to be associated with direct permeability effects of the hormone. Maximum water transport occurs at a higher dose of vasopressin (100 mU/ml) over a concentration range associated with hormone-stimulated adenylate cyclase activity. The water transport response to low doses of vasopressin may be potentiated by aldosterone treatment, an effect that can be related to the inhibition of tissue phosphodiesterase activity and subsequent increased cyclic AMP concentrations. In steroid depleted conditions the cyclic AMP medicate efflux of mitochondrial calcium ions, that occurs at low doses of vasopressin, may prevent the release of membrane bound calcium ions and thus inhibit the water permeability effect of the hormone. Higher levels of cyclic AMP reverse this inhibitory effect and give rise to an increased water flow. It is concluded that cyclic AMP and intracellular concentrations of calcium ion act as inter-related mediators of antidiuretic hormone action.", "contents": "Role of mitochondrial Ca2+ in antidiuretic hormone action. The calcium ion concentration measured in rat kidney mitochondria, isolated from vasopressin treated tissue, has a dose response characteristic in which the calcium concentration reached a minimum at low doses of vasopressin (2 mU/ml), at higher doses of hormone the mitochondrial calcium ion concentration increases reaching a value close to that of the controls with vasopressin (100 mU/ml). This efflux and subsequent uptake of mitochondrial calcium has been shown to be a direct effect of the varying cyclic AMP concentrations. Sodium and water permeability effects of vasopressin have been shown in toad bladder to have different dose response characteristics. Maximum sodium transport occurs at a lower dose of vasopressin (2 mU/ml) and is believed to be associated with direct permeability effects of the hormone. Maximum water transport occurs at a higher dose of vasopressin (100 mU/ml) over a concentration range associated with hormone-stimulated adenylate cyclase activity. The water transport response to low doses of vasopressin may be potentiated by aldosterone treatment, an effect that can be related to the inhibition of tissue phosphodiesterase activity and subsequent increased cyclic AMP concentrations. In steroid depleted conditions the cyclic AMP medicate efflux of mitochondrial calcium ions, that occurs at low doses of vasopressin, may prevent the release of membrane bound calcium ions and thus inhibit the water permeability effect of the hormone. Higher levels of cyclic AMP reverse this inhibitory effect and give rise to an increased water flow. It is concluded that cyclic AMP and intracellular concentrations of calcium ion act as inter-related mediators of antidiuretic hormone action."}
{"id": "PMID:187380", "title": "Effect of an ammonia load on the kidney near-equilibrium systems in the rat in vivo.", "content": "1)The time course of changes in concentration of renal metabolites in response to a non-toxic load of NH4 as NH4 Cl or NH4HCO3 were measured in fasted rats. 2) Following a NH4Cl load, decrease of renal concentration of 2-oxoglutarate occurs but this change is delayed in relation to the peak of the blood ammonia concentration and persists after disappearance of the hyperammoniemia. 3) Following a NH4HCO3 load, the oxoglutarate concentration changes are less marked and more transient. 4) No close relationship between the mitochondrial free NAD/NADH ratio calculated from the glutamate dehydrogenase and the 3-hydroxybutyrate dehydrogenase systems were seen during alteration of the ammonia concentration. 5) Contrary to the observations in the liver under similar circumstances (BROSNAN, J.T. et al.: Biochem.J. 138, 453, 1974), no increase in kidney tissue or renal venous blood alanine or aspartate concentration are seen. 6) A constant infusion of NH4HCO3 resulted only in an increase in tissue and renal venous blood glutamine concentration. 7) The infusion of NH4 together with a carbon source (malate) resulted in a similar increase in tissue glutamine concentration and more striking increase in renal venous glutamine concentration. No accumulation of aspartate nor alanine were seen. 8) In vitro studies indicate that the net flux through both the aspartate aminotransferase and the glutamate dehydrogenase reactions is dependent on the concentration of the reactants as expected for a near-equilibrium system. 9) It is concluded that the kidney response to an ammonia load differs from that of the liver despite the existence of a similar network of near-equilibrium reactions of (1) a lack of local availability of oxaloacetate, (2) a lower activity of alanine aminotransferase, (3) a greater in vivo activity of glutamine synthetase.", "contents": "Effect of an ammonia load on the kidney near-equilibrium systems in the rat in vivo. 1)The time course of changes in concentration of renal metabolites in response to a non-toxic load of NH4 as NH4 Cl or NH4HCO3 were measured in fasted rats. 2) Following a NH4Cl load, decrease of renal concentration of 2-oxoglutarate occurs but this change is delayed in relation to the peak of the blood ammonia concentration and persists after disappearance of the hyperammoniemia. 3) Following a NH4HCO3 load, the oxoglutarate concentration changes are less marked and more transient. 4) No close relationship between the mitochondrial free NAD/NADH ratio calculated from the glutamate dehydrogenase and the 3-hydroxybutyrate dehydrogenase systems were seen during alteration of the ammonia concentration. 5) Contrary to the observations in the liver under similar circumstances (BROSNAN, J.T. et al.: Biochem.J. 138, 453, 1974), no increase in kidney tissue or renal venous blood alanine or aspartate concentration are seen. 6) A constant infusion of NH4HCO3 resulted only in an increase in tissue and renal venous blood glutamine concentration. 7) The infusion of NH4 together with a carbon source (malate) resulted in a similar increase in tissue glutamine concentration and more striking increase in renal venous glutamine concentration. No accumulation of aspartate nor alanine were seen. 8) In vitro studies indicate that the net flux through both the aspartate aminotransferase and the glutamate dehydrogenase reactions is dependent on the concentration of the reactants as expected for a near-equilibrium system. 9) It is concluded that the kidney response to an ammonia load differs from that of the liver despite the existence of a similar network of near-equilibrium reactions of (1) a lack of local availability of oxaloacetate, (2) a lower activity of alanine aminotransferase, (3) a greater in vivo activity of glutamine synthetase."}
{"id": "PMID:187382", "title": "Regulation of phosphoenolpyruvate carboxykinase by glutamine and ATP as possible control mechanisms of renal gluconeogenesis.", "content": "In different metabolic states renal phosphoenolpyruvate carboxykinase (PEP-CK) activities are closely correlated with in vitro glucogenic rates, suggesting a limitation of the glucogenic capacity of kidney by this enzyme. Stimulation of renal gluconeogenesis from pyruvate, lactate, and succinate by lysine and glutamine was therefore associated with a regulatory attack of these amino acids at the level of PEP-carboxykinase. This postulate was confirmed by the failure of lysine to stimulate glucose synthesis from fructose. Experimental support for an interference of glutamine and PEP-carboxykinase was obtained by a study on the inactivation of this enzyme in kidney cortex homogenates: A rapid inactivation of enzyme activity within 40-50 min could be slowed down by glutamine. In addition the inactivation was counteracted by ATP. At suboptimal concentrations of the trinucleotide its effect was potentiated by c-AMP and c-GMP. Studies on the effect of ATP on PEP-carboxykinase in kidney cortex homogenates from rats in different metabolic states revealed: In homogenates from carbohydrate fed animals extreme low activities of PEP-CK were not altered by ATP, whereas elevated enzyme activities after a protein rich diet could be further raised by a factor of 2 or 3 by ATP. GTP and ITP could substitute for ATP. An extension of these studies on hepatic enzymes showed a similar inactivation of tyrosine aminotransferase (TAT) and a protective effect of ATP. The data obtained from these experiments favour an interconversion of PEP-carboxykinase and tyrosine aminotransferase into different forms as possible mechanism for their regulation.", "contents": "Regulation of phosphoenolpyruvate carboxykinase by glutamine and ATP as possible control mechanisms of renal gluconeogenesis. In different metabolic states renal phosphoenolpyruvate carboxykinase (PEP-CK) activities are closely correlated with in vitro glucogenic rates, suggesting a limitation of the glucogenic capacity of kidney by this enzyme. Stimulation of renal gluconeogenesis from pyruvate, lactate, and succinate by lysine and glutamine was therefore associated with a regulatory attack of these amino acids at the level of PEP-carboxykinase. This postulate was confirmed by the failure of lysine to stimulate glucose synthesis from fructose. Experimental support for an interference of glutamine and PEP-carboxykinase was obtained by a study on the inactivation of this enzyme in kidney cortex homogenates: A rapid inactivation of enzyme activity within 40-50 min could be slowed down by glutamine. In addition the inactivation was counteracted by ATP. At suboptimal concentrations of the trinucleotide its effect was potentiated by c-AMP and c-GMP. Studies on the effect of ATP on PEP-carboxykinase in kidney cortex homogenates from rats in different metabolic states revealed: In homogenates from carbohydrate fed animals extreme low activities of PEP-CK were not altered by ATP, whereas elevated enzyme activities after a protein rich diet could be further raised by a factor of 2 or 3 by ATP. GTP and ITP could substitute for ATP. An extension of these studies on hepatic enzymes showed a similar inactivation of tyrosine aminotransferase (TAT) and a protective effect of ATP. The data obtained from these experiments favour an interconversion of PEP-carboxykinase and tyrosine aminotransferase into different forms as possible mechanism for their regulation."}
{"id": "PMID:187383", "title": "The mode of activation and regulation of glutaminase in intact kidney mitochondria.", "content": "Experiments were carried out with isolated pig renal-cortex and rat kidney mitochondria. Respiration, glutaminase activity and swelling of the mitochondria were followed by an oxygen electrode, an NH+4-sensitive electrode and spectrophotometrically. The inhibitors of the transport of glutamate (avenaciolide) and phosphate (mersalyl) across the inner mitochondrial membrane were employed. On the basis of the experimental findings we made the following conclusions: 1. There are two mechanisms by which glutamate can leave the inner space of kidney mitochondria: (a) an electrogenic efflus coupled to the respiration driven proton translocation and the presence of a membrane potential (positive outside), and (b) an electroneutral glutamate-hydroxyl exchange which is inhibited by avenaciolide and which operates in both directions. 2. The activation of glutaminase in intact mitochondria by phosphate occurs only if the activator moves across the inner mitochondrial membrane. The enzyme can be activated even when the movement of phosphate is inhibited provided that the mitochondria are energized. 3. Glutaminase is intimely associated with the inner mitochondrial membrane so that the part of the enzyme with the binding site for phosphate is embedded in the membrane, whereas the part with the binding sites for the substrate and glutamate is exposed toward the matrix space. The mechanism of allosteric activation of glutaminase and of the efflux of glutamate from mitochondria are probably the crucial factors which regulate the enzyme activity, and, consequently, renal ammoniagenesis in vivo.", "contents": "The mode of activation and regulation of glutaminase in intact kidney mitochondria. Experiments were carried out with isolated pig renal-cortex and rat kidney mitochondria. Respiration, glutaminase activity and swelling of the mitochondria were followed by an oxygen electrode, an NH+4-sensitive electrode and spectrophotometrically. The inhibitors of the transport of glutamate (avenaciolide) and phosphate (mersalyl) across the inner mitochondrial membrane were employed. On the basis of the experimental findings we made the following conclusions: 1. There are two mechanisms by which glutamate can leave the inner space of kidney mitochondria: (a) an electrogenic efflus coupled to the respiration driven proton translocation and the presence of a membrane potential (positive outside), and (b) an electroneutral glutamate-hydroxyl exchange which is inhibited by avenaciolide and which operates in both directions. 2. The activation of glutaminase in intact mitochondria by phosphate occurs only if the activator moves across the inner mitochondrial membrane. The enzyme can be activated even when the movement of phosphate is inhibited provided that the mitochondria are energized. 3. Glutaminase is intimely associated with the inner mitochondrial membrane so that the part of the enzyme with the binding site for phosphate is embedded in the membrane, whereas the part with the binding sites for the substrate and glutamate is exposed toward the matrix space. The mechanism of allosteric activation of glutaminase and of the efflux of glutamate from mitochondria are probably the crucial factors which regulate the enzyme activity, and, consequently, renal ammoniagenesis in vivo."}
{"id": "PMID:187388", "title": "Mitochondrial abnormalities in progressive ophthalmoplegia.", "content": "A clinically diagnosed case of progressive external ophthalmoplegia was biopsied and ultrastructurally evaluated. The disease was found to be characterized by numerous giant mitochondria. The intramitochondrial changes consisted of either swirls of cristae or of paracrystalline structures which were in apposition with the membranes of the cristae. The internal structure of the paracrystalline units consisted of parallel bands of material which were aligned in the same plane as the membranes of the related cristae.", "contents": "Mitochondrial abnormalities in progressive ophthalmoplegia. A clinically diagnosed case of progressive external ophthalmoplegia was biopsied and ultrastructurally evaluated. The disease was found to be characterized by numerous giant mitochondria. The intramitochondrial changes consisted of either swirls of cristae or of paracrystalline structures which were in apposition with the membranes of the cristae. The internal structure of the paracrystalline units consisted of parallel bands of material which were aligned in the same plane as the membranes of the related cristae."}
{"id": "PMID:187389", "title": "Electron microscopy of the cotton fibre: new observations on cell wall formation.", "content": "The ultrastructure of the cotton fibres was examined after developing successful fixation methods. Fibre cells were fixed at different stages of development. In cells which were elongating and producing primary cell walls, the Golgi apparatus appeared to be directly involved in secretion and synthesis of primary wall components. In cells which were synthesizing thick secondary cell walls, evidence suggested a major role for the endoplasmic reticulum and plasma memebrane in the synthesis and secretion of secondary wall materials. The possibility of a shift from a Golgi apparatus pathway for primary wall synthesis to an endoplasmic reticulum pathway for secondary wall synthesis is discussed. Plasma membrane micro-invaginations are present only during secondary wall synthesis and may represent sites of cellulose assembly. A model for primary wall biogenesis via the Golgi apparatus is presented, and the potential of the cotton fibre as a model system for studying cellulose biogenesis in higher plants is discussed.", "contents": "Electron microscopy of the cotton fibre: new observations on cell wall formation. The ultrastructure of the cotton fibres was examined after developing successful fixation methods. Fibre cells were fixed at different stages of development. In cells which were elongating and producing primary cell walls, the Golgi apparatus appeared to be directly involved in secretion and synthesis of primary wall components. In cells which were synthesizing thick secondary cell walls, evidence suggested a major role for the endoplasmic reticulum and plasma memebrane in the synthesis and secretion of secondary wall materials. The possibility of a shift from a Golgi apparatus pathway for primary wall synthesis to an endoplasmic reticulum pathway for secondary wall synthesis is discussed. Plasma membrane micro-invaginations are present only during secondary wall synthesis and may represent sites of cellulose assembly. A model for primary wall biogenesis via the Golgi apparatus is presented, and the potential of the cotton fibre as a model system for studying cellulose biogenesis in higher plants is discussed."}
{"id": "PMID:187390", "title": "Plastoglobules of leaf chloroplasts of two cultivars of Capsicum annuum.", "content": "The chloroplasts of the leaves of Capsicum annuum cv. Purple Leaf Cherry are characterized by the presence of large electron translucent plastoglobules which comprise a considerable proportion of the plastid volume. The leaf chloroplasts of Purple Leaf Yellow cultivar contain, in addition, large starch granules which are frequently in intimate association with these plastoglobules. There appears to be a controlled expulsion of plastoglobules into the vacuole by the non-degenerating chloroplasts of both cultivars, although the function of this secretion is not known. The chloroplasts of older leaves of Purple Leaf Yellow also contain plastoglobules with a nonhomogenous fine structure. Some have granular segments, membrane-like bands, or myelin-like bands, the latter suggesting the presence of glyco- and/or phospholipids in such plastoglobules.", "contents": "Plastoglobules of leaf chloroplasts of two cultivars of Capsicum annuum. The chloroplasts of the leaves of Capsicum annuum cv. Purple Leaf Cherry are characterized by the presence of large electron translucent plastoglobules which comprise a considerable proportion of the plastid volume. The leaf chloroplasts of Purple Leaf Yellow cultivar contain, in addition, large starch granules which are frequently in intimate association with these plastoglobules. There appears to be a controlled expulsion of plastoglobules into the vacuole by the non-degenerating chloroplasts of both cultivars, although the function of this secretion is not known. The chloroplasts of older leaves of Purple Leaf Yellow also contain plastoglobules with a nonhomogenous fine structure. Some have granular segments, membrane-like bands, or myelin-like bands, the latter suggesting the presence of glyco- and/or phospholipids in such plastoglobules."}
{"id": "PMID:187393", "title": "Bronchilar carcinoma in a 20-year-old man.", "content": "A 20-year-old man with a nine-month history of pulmonary abscess and hemoptysis was discovered to have a small nidus of bronchiolar carcinoma in the fibrotic reaction surrounding the pulmonary abscess. The cell type, origin, and occurrence of this tumor in fibrotic pulmonary disease are discussed. We believe that this case represents an unusual presentation of bronchiolar carcinoma with respect to clinical manifestation, tumor size, and patient's age.", "contents": "Bronchilar carcinoma in a 20-year-old man. A 20-year-old man with a nine-month history of pulmonary abscess and hemoptysis was discovered to have a small nidus of bronchiolar carcinoma in the fibrotic reaction surrounding the pulmonary abscess. The cell type, origin, and occurrence of this tumor in fibrotic pulmonary disease are discussed. We believe that this case represents an unusual presentation of bronchiolar carcinoma with respect to clinical manifestation, tumor size, and patient's age."}
{"id": "PMID:187394", "title": "Chronic eosinophilic pneumonia. Ultrastructural evidence of marked immunoglobulin production plus macrophagic ingestion of eosinophils and eosinophilic lysosomes leading to intracytoplasmic Charcot-Leyden crystals.", "content": "A 60-year-old man was diagnosed as having chronic eosinophilic pneumonia by clinical presentation and open lung biopsy. Electron microscopic study of the tissue from biopsy revealed evidence of marked production of immunoglobulin, which may be part of the chemotactic process which attracted large numbers of eosinophils into the area. Also, there were macrophages which were phagocytosing degenerating eosinophils and eosinophilic lysosomes. Charcot-Leyden crystals were noted in the cytoplasm of many macrophages. The relationship of the production of immunoglobulin to the eosinophilia and the mechanism of intramacrophagic formation of Charcot-Leyden crystals is discussed.", "contents": "Chronic eosinophilic pneumonia. Ultrastructural evidence of marked immunoglobulin production plus macrophagic ingestion of eosinophils and eosinophilic lysosomes leading to intracytoplasmic Charcot-Leyden crystals. A 60-year-old man was diagnosed as having chronic eosinophilic pneumonia by clinical presentation and open lung biopsy. Electron microscopic study of the tissue from biopsy revealed evidence of marked production of immunoglobulin, which may be part of the chemotactic process which attracted large numbers of eosinophils into the area. Also, there were macrophages which were phagocytosing degenerating eosinophils and eosinophilic lysosomes. Charcot-Leyden crystals were noted in the cytoplasm of many macrophages. The relationship of the production of immunoglobulin to the eosinophilia and the mechanism of intramacrophagic formation of Charcot-Leyden crystals is discussed."}
{"id": "PMID:187395", "title": "Discharge planning in foster care cases where the father is the significant parent.", "content": "In planning for the discharge from foster care of children in one-parent families, the potential of fathers is often neglected. An agency study indicates that intensive casework and adequate services can make the return to fathers appropriate.", "contents": "Discharge planning in foster care cases where the father is the significant parent. In planning for the discharge from foster care of children in one-parent families, the potential of fathers is often neglected. An agency study indicates that intensive casework and adequate services can make the return to fathers appropriate."}
{"id": "PMID:187398", "title": "[Nasal application of a synthetic alpha1-18 corticotropin: an effective form of ACTH treatment (author's transl)].", "content": "The absorption of a synthetic ACTH-peptide (alpha1-18 corticotropin, Ba 41.795) via the nasal mucosa was investigated in twelve probands. After application of 1 mg into each nostril a rapid increase of the plasma cortisol was observed which returned to the initial value only after 7 hours. In two patients with rheumatoid arthritis and two patients with bronchial asthma who had been treated with regular steroid injections an attempt was made to replace the injections by nasal application. The same therapeutic effects could be obtained, but larger doses were required than when using injection therapy.", "contents": "[Nasal application of a synthetic alpha1-18 corticotropin: an effective form of ACTH treatment (author's transl)]. The absorption of a synthetic ACTH-peptide (alpha1-18 corticotropin, Ba 41.795) via the nasal mucosa was investigated in twelve probands. After application of 1 mg into each nostril a rapid increase of the plasma cortisol was observed which returned to the initial value only after 7 hours. In two patients with rheumatoid arthritis and two patients with bronchial asthma who had been treated with regular steroid injections an attempt was made to replace the injections by nasal application. The same therapeutic effects could be obtained, but larger doses were required than when using injection therapy."}
{"id": "PMID:187403", "title": "Regulation of lactogenic hormone binding in rat liver by steroid hormones.", "content": "We have measured the effects of testosterone propionate, medroxy-progesterone acetate and cortisol on the binding of ovine [125I]iodoprolactin to 100,000 X g particulate fractions from liver of normal and estrogen-treated female rats. In untreated animals 6.7 +/- 1.1% (SD) of the radioactivity added to 0.5 mg of membrane protein was specifically bound to the hormone receptor. Specific binding was significantly (P less than .05) decreased after 7 daily doses of testosterone (1.0 mg) to 2.8 +/- 1.4%, medroxyprogesterone (0.25 mg) to 2.7 +/- 0.2% and cortisol (5.0 mg) to 3.1 +/- 1.3%. The serum prolactin concentration, 4.2 +/- 3.4 ng/ml in normal animals, was not affected by the hormone treatment. Ethinyl estradiol, 10 mug/day for 7 days, increasing the binding of [125I]iodo-prolactin to 16.6 +/- 6.0% and increased serum prolactin to 50.6 +/- 11.5 ng/ml. Simultaneous administration of testosterone, medroxyprogesterone or cortisol with estradiol did not diminish the estradiol-induced increase in serum prolactin, but completely prevented the increase in prolactin binding. Testosterone or cortisol given to animals pretreated with estradiol suppressed prolactin binding from 16.4 +/- 4.2% to less than 2.5% after 48-72 h. Parellel results were obtained with 125I labeled human growth hormone whereas 125I labeled-insulin binding was not affected by these treatments. Scatchard analysis showed that the decrease in lactogenic hormone binding was due to a reduced concentration of receptors with no significant change in affinity. Since serum levels of prolactin were not changed, we conclude that treatment with testosterone, medroxyprogesterone, and cortisol decreased lactogenic hormone binding by a direct action on the liver.", "contents": "Regulation of lactogenic hormone binding in rat liver by steroid hormones. We have measured the effects of testosterone propionate, medroxy-progesterone acetate and cortisol on the binding of ovine [125I]iodoprolactin to 100,000 X g particulate fractions from liver of normal and estrogen-treated female rats. In untreated animals 6.7 +/- 1.1% (SD) of the radioactivity added to 0.5 mg of membrane protein was specifically bound to the hormone receptor. Specific binding was significantly (P less than .05) decreased after 7 daily doses of testosterone (1.0 mg) to 2.8 +/- 1.4%, medroxyprogesterone (0.25 mg) to 2.7 +/- 0.2% and cortisol (5.0 mg) to 3.1 +/- 1.3%. The serum prolactin concentration, 4.2 +/- 3.4 ng/ml in normal animals, was not affected by the hormone treatment. Ethinyl estradiol, 10 mug/day for 7 days, increasing the binding of [125I]iodo-prolactin to 16.6 +/- 6.0% and increased serum prolactin to 50.6 +/- 11.5 ng/ml. Simultaneous administration of testosterone, medroxyprogesterone or cortisol with estradiol did not diminish the estradiol-induced increase in serum prolactin, but completely prevented the increase in prolactin binding. Testosterone or cortisol given to animals pretreated with estradiol suppressed prolactin binding from 16.4 +/- 4.2% to less than 2.5% after 48-72 h. Parellel results were obtained with 125I labeled human growth hormone whereas 125I labeled-insulin binding was not affected by these treatments. Scatchard analysis showed that the decrease in lactogenic hormone binding was due to a reduced concentration of receptors with no significant change in affinity. Since serum levels of prolactin were not changed, we conclude that treatment with testosterone, medroxyprogesterone, and cortisol decreased lactogenic hormone binding by a direct action on the liver."}
{"id": "PMID:187404", "title": "Circadian patterns of stress-induced ACTH secretion are modified by corticosterone responses.", "content": "To test whether there is a circadian rhythm in the ACTH response to stress, young female rats were exposed to a variety of ACTH-releasing stimuli at 0600 and 1800 h and changes in circulating ACTH and corticosterone were measured. The results of these experiments suggested that after the high intensity stimuli of laparotomy with intestinal traction or 250 mug histamine ip/100 g BW, the morning ACTH response was greater than the evening response. However, the ACTH response to ip saline was greater in the evening in one experiment and greater in the morning in a second experiment. Plasma corticosterone responses were faster and greater in the morning in the first experiment and in the evening in the second experiment. The ACTH response to 125 mug histamine ip/100 g BW was greater in the evening and the change in corticosterone was greater in the morning. Thus, after low intensity stimuli, the ACTH responses appeared to depend on both the lag time prior to the corticosterone response, and its magnitude. To test this possibility, rats were adrenalectomized and the ACTH response was measured 7.5 and 15 min after the start of surgery and after injection with either 2% EtOH-saline, or 50 mug corticosterone at operation, or with 30 mug corticosterone at 5 min. Compared with ACTH levels in rats treated with vehicle, ACTH levels were decreased 7.5 min after 50 mug corticosterone at operation (P less than 0.01), but not after 30 mug corticosterone at 5 min. ACTH levels were slightly reduced 10 min after 30 mug corticosterone at 5 min compared with those of rats injected with vehicle at operation (P less than 0.05). These results are consistent with the interpretation that corticosterone secretion modifies stress-induced ACTH secretion via the fast-feedback effect. Comparison of the ACTH responses to acute adrenalectomy plus injection with EtOH-saline at 0600 and 1800 h demonstrated that, in the absence of a corticosterone response to the stress, the ACTH response is greater in the morning that in the evening (P less than 0.01). Finally, this group of experiments suggests strongly that the responsivenss of rat adrenal glands to ACTH increases markedly between 0600 and 1800 h.", "contents": "Circadian patterns of stress-induced ACTH secretion are modified by corticosterone responses. To test whether there is a circadian rhythm in the ACTH response to stress, young female rats were exposed to a variety of ACTH-releasing stimuli at 0600 and 1800 h and changes in circulating ACTH and corticosterone were measured. The results of these experiments suggested that after the high intensity stimuli of laparotomy with intestinal traction or 250 mug histamine ip/100 g BW, the morning ACTH response was greater than the evening response. However, the ACTH response to ip saline was greater in the evening in one experiment and greater in the morning in a second experiment. Plasma corticosterone responses were faster and greater in the morning in the first experiment and in the evening in the second experiment. The ACTH response to 125 mug histamine ip/100 g BW was greater in the evening and the change in corticosterone was greater in the morning. Thus, after low intensity stimuli, the ACTH responses appeared to depend on both the lag time prior to the corticosterone response, and its magnitude. To test this possibility, rats were adrenalectomized and the ACTH response was measured 7.5 and 15 min after the start of surgery and after injection with either 2% EtOH-saline, or 50 mug corticosterone at operation, or with 30 mug corticosterone at 5 min. Compared with ACTH levels in rats treated with vehicle, ACTH levels were decreased 7.5 min after 50 mug corticosterone at operation (P less than 0.01), but not after 30 mug corticosterone at 5 min. ACTH levels were slightly reduced 10 min after 30 mug corticosterone at 5 min compared with those of rats injected with vehicle at operation (P less than 0.05). These results are consistent with the interpretation that corticosterone secretion modifies stress-induced ACTH secretion via the fast-feedback effect. Comparison of the ACTH responses to acute adrenalectomy plus injection with EtOH-saline at 0600 and 1800 h demonstrated that, in the absence of a corticosterone response to the stress, the ACTH response is greater in the morning that in the evening (P less than 0.01). Finally, this group of experiments suggests strongly that the responsivenss of rat adrenal glands to ACTH increases markedly between 0600 and 1800 h."}
{"id": "PMID:187405", "title": "Interaction of human growth hormone with isolated rat liver cells.", "content": "The interaction of 125I-labeled human growth hormone (hGH) with isolated rat liver cells is a specific, time dependent and saturable process. In male rats, one cell binds a maximum of 2000 hormone molecules; the dissociation constant of the cell-hGH interaction is about 3 X 10(-10)M. Liver cells of female rats bind 5 to 10 times more hGH than do those of male rats at equivalent hormone concentrations. Binding of 125I-labeled hGH to liver cells is readily inhibited by native hGH; 50% inhibition occurs at about 2 X 10(-9)M hGH irrespective of sex. In male rats, bovine growth hormone (bGH) is almost as potent as hGH in inhibiting 125I-labeled hGH binding; no displacement occurs with ovine prolactin (oPRL) except at very high (greater than 10(-6)M) concentrations. In female rats, bGH competes less effectively, and oPRL, more effectively, than they do in males; in addition, oPRL demonstrates a higher apparent affinity for the hGH binding sites (4 X 10(-9)M) than does bGH (1 X 10(-8M). These findings suggest that in female rats hGH, unlike bGH, interacts with additional, \"lactogenic\" binding sites that are distinct from the \"growth hormone\" binding sites. The 125I-labeled hGH eluted from liver cells as well as that which remains in the incubation medium retains full biological activity, as judged on its ability to bind specifically to liver membranes. Treatment of liver cells by phospholipase A causes a 5-fold increase in cell binding capacity. Liver cells bind about the same amount of hGH as do crude particulate fractions from these cells; this suggests that in the intact cell, binding occurs at relatively accessible sites, presumably localized in the plasma membrane.", "contents": "Interaction of human growth hormone with isolated rat liver cells. The interaction of 125I-labeled human growth hormone (hGH) with isolated rat liver cells is a specific, time dependent and saturable process. In male rats, one cell binds a maximum of 2000 hormone molecules; the dissociation constant of the cell-hGH interaction is about 3 X 10(-10)M. Liver cells of female rats bind 5 to 10 times more hGH than do those of male rats at equivalent hormone concentrations. Binding of 125I-labeled hGH to liver cells is readily inhibited by native hGH; 50% inhibition occurs at about 2 X 10(-9)M hGH irrespective of sex. In male rats, bovine growth hormone (bGH) is almost as potent as hGH in inhibiting 125I-labeled hGH binding; no displacement occurs with ovine prolactin (oPRL) except at very high (greater than 10(-6)M) concentrations. In female rats, bGH competes less effectively, and oPRL, more effectively, than they do in males; in addition, oPRL demonstrates a higher apparent affinity for the hGH binding sites (4 X 10(-9)M) than does bGH (1 X 10(-8M). These findings suggest that in female rats hGH, unlike bGH, interacts with additional, \"lactogenic\" binding sites that are distinct from the \"growth hormone\" binding sites. The 125I-labeled hGH eluted from liver cells as well as that which remains in the incubation medium retains full biological activity, as judged on its ability to bind specifically to liver membranes. Treatment of liver cells by phospholipase A causes a 5-fold increase in cell binding capacity. Liver cells bind about the same amount of hGH as do crude particulate fractions from these cells; this suggests that in the intact cell, binding occurs at relatively accessible sites, presumably localized in the plasma membrane."}
{"id": "PMID:187406", "title": "Stimulation in vivo of the secretion of prolactin and growth hormone by beta-endorphin.", "content": "Morphine sulfate (MS) and the opioid peptide beta-endorphin beta-LPH-(61-91) stimulate prolactin and growth hormone release in steroid-primed and non-treated male rats when injected intravenously or intracisternally. On a molar basis beta-endorphin is at least 20 times more potent than MS, whereas Met5-enkephalin (beta-LPH-(61-65)) and alpha-endorphin (beta-LPH-(61-76)) are devoid of activity at the dose injected (300 mug). The in vivo stimulatory effects of beta-endorphin on prolactin secretion are reversed by the opiate antagonist naloxone. The absence of in vitro effect of MS and beta-endorphin on prolactin and growth hormone secretion by cultured rat pituitary cells suggest that they have a central nervous system site of action.", "contents": "Stimulation in vivo of the secretion of prolactin and growth hormone by beta-endorphin. Morphine sulfate (MS) and the opioid peptide beta-endorphin beta-LPH-(61-91) stimulate prolactin and growth hormone release in steroid-primed and non-treated male rats when injected intravenously or intracisternally. On a molar basis beta-endorphin is at least 20 times more potent than MS, whereas Met5-enkephalin (beta-LPH-(61-65)) and alpha-endorphin (beta-LPH-(61-76)) are devoid of activity at the dose injected (300 mug). The in vivo stimulatory effects of beta-endorphin on prolactin secretion are reversed by the opiate antagonist naloxone. The absence of in vitro effect of MS and beta-endorphin on prolactin and growth hormone secretion by cultured rat pituitary cells suggest that they have a central nervous system site of action."}
{"id": "PMID:187407", "title": "(Des-Asp1) angiotensin I: a study of its pressor and steroidogenic activities in conscious rats.", "content": "The steroidogenic and pressor activities of the nonapeptide (des-Asp1) angiotensin I [(des-Asp)-AI] were tested in conscious rats. (des-Asp)-AI caused dose related increases in mean arterial pressure (MAP), serum aldosterone, and serum corticosterone in doses between 3 and 3,000 ng/kg/min. (des-Asp)-AI was 14% as potent as angiotensin I and angiotensin II and 60% as potent as (des-Asp1) angiotensin II [des-Asp)-AII] in raising MAP. (des-Asp)-AI was less active than AI, AII, or (des-Asp)-AII in causing increased release of aldosterone, possessing only 8%, 11%, and 17% of the potency of AII, (des-Asp)-AII, and AI, respectively. Each of these angiotensin peptides was equally potent in elevating serum corticosterone levels. Infusions of a nonapeptide inhibitor of converting enzyme (CEI, 0.5 mg/kg/min iv) did not alter control MAP or blood pressure responses to AII or (des-Asp-)-AII but inhibited equally the blood pressure effects of AI and (des-Asp)-AI. CEI also inhibited the ability of (des-Asp)-AI (67% inhibition) and AI (34% inhibition) to increase the serum aldosterone concentration, but had no effect on basal aldosterone levels. These data indicate that (des-Asp)-AI has pressor and steroidogenic effects, but requires conversion to (des-Asp)-AII for a major portion of its activity. These results further substantiate the hypothesis that (des-Asp)-AII, recently recognized as a hormone of the renin-angiotensin system, may be produced without the formation of AII as an intermediate and provide in vivo evidence for the conversion of (des-Asp)-AI to (des-Asp)-AII.", "contents": "(Des-Asp1) angiotensin I: a study of its pressor and steroidogenic activities in conscious rats. The steroidogenic and pressor activities of the nonapeptide (des-Asp1) angiotensin I [(des-Asp)-AI] were tested in conscious rats. (des-Asp)-AI caused dose related increases in mean arterial pressure (MAP), serum aldosterone, and serum corticosterone in doses between 3 and 3,000 ng/kg/min. (des-Asp)-AI was 14% as potent as angiotensin I and angiotensin II and 60% as potent as (des-Asp1) angiotensin II [des-Asp)-AII] in raising MAP. (des-Asp)-AI was less active than AI, AII, or (des-Asp)-AII in causing increased release of aldosterone, possessing only 8%, 11%, and 17% of the potency of AII, (des-Asp)-AII, and AI, respectively. Each of these angiotensin peptides was equally potent in elevating serum corticosterone levels. Infusions of a nonapeptide inhibitor of converting enzyme (CEI, 0.5 mg/kg/min iv) did not alter control MAP or blood pressure responses to AII or (des-Asp-)-AII but inhibited equally the blood pressure effects of AI and (des-Asp)-AI. CEI also inhibited the ability of (des-Asp)-AI (67% inhibition) and AI (34% inhibition) to increase the serum aldosterone concentration, but had no effect on basal aldosterone levels. These data indicate that (des-Asp)-AI has pressor and steroidogenic effects, but requires conversion to (des-Asp)-AII for a major portion of its activity. These results further substantiate the hypothesis that (des-Asp)-AII, recently recognized as a hormone of the renin-angiotensin system, may be produced without the formation of AII as an intermediate and provide in vivo evidence for the conversion of (des-Asp)-AI to (des-Asp)-AII."}
{"id": "PMID:187408", "title": "Evidence for the existence of a histamine H2-receptor in the mouse thyroid.", "content": "The existence of a histamine H2-receptor in the thyroid was investigated. Histamine in vitro stimulated the formation of cyclic AMP and colloid droplet formation in mouse thyroid lobes. Stimulation by histamine of cyclic AMP formation in mouse thyroid lobes was significantly inhibited by metiamide, a histamine H2-receptor antagonist. 4-Methylhistamine, a histamine H2-receptor agonist, markedly stimulated cyclic AMP formation, whereas 2-methylhistamine, a histamine H1-receptor agonist, was ineffective. The stimulation by 4-methylhistamine of cyclic AMP formation was markedly inhibited by metiamide, but not by chlorpheniramine, a histamine H1-receptor antagonist. In contrast, metiamide did not affect cyclic AMP formation induced either by TSH or by the long-acting thyroid stimulator. Therefore, it is suggested that there exists a histamine H2-receptor in the membranes of the thyroid follicular cells which facilitate thyroid hormone secretion via the adenylate cyclase-cyclic AMP system.", "contents": "Evidence for the existence of a histamine H2-receptor in the mouse thyroid. The existence of a histamine H2-receptor in the thyroid was investigated. Histamine in vitro stimulated the formation of cyclic AMP and colloid droplet formation in mouse thyroid lobes. Stimulation by histamine of cyclic AMP formation in mouse thyroid lobes was significantly inhibited by metiamide, a histamine H2-receptor antagonist. 4-Methylhistamine, a histamine H2-receptor agonist, markedly stimulated cyclic AMP formation, whereas 2-methylhistamine, a histamine H1-receptor agonist, was ineffective. The stimulation by 4-methylhistamine of cyclic AMP formation was markedly inhibited by metiamide, but not by chlorpheniramine, a histamine H1-receptor antagonist. In contrast, metiamide did not affect cyclic AMP formation induced either by TSH or by the long-acting thyroid stimulator. Therefore, it is suggested that there exists a histamine H2-receptor in the membranes of the thyroid follicular cells which facilitate thyroid hormone secretion via the adenylate cyclase-cyclic AMP system."}
{"id": "PMID:187409", "title": "Further studies on the mechanisms controlling prostaglandin biosynthesis in the cat adrenal cortex: the role of calcium and cyclic AMP.", "content": "In light of previous studies which have implicated prostaglandin (PG) formation as a link in ACTH-induced steroid production by isolated cat adrenocortical cells, experiments were carried out to provide additional information regarding the role of PGs in adrenal steroidogenesis and their interactions with calcium and cyclic AMP. Perfusion of cat adrenal glands with Locke's solution plus beta(1-24)-ACTH resulted in an immediate increase in PGF2alpha release, which rapidly declined to basal levels after the stimulus was withdrawn. In contrast, maximal rates of steroid release were manifest some 30 min after removal of ACTH. ACTH and its onitrophenyl sulfenyl derivative (NPS-ACTH) increased PG (PGF2alpha and PGE2) and steroid release by trypsin-dispersed cat cortical cells, but NPS-ACTH, unlike ACTH, did not augment cortical cyclic AMP levels. In this same preparation, indomethacin completely blocked ACTH and NPS-ACTH facilitated PGF2alpha and PGE2 release but failed to suppress steroid release markedly. Calcium-deprivation blocked PG and steroid release evoked by these two polypeptides, and depressed PG release elicited by monobutyryl cyclic AMP (bcAMP) without affecting steroid release. These experiments offer additional evidence to support the concept that PGs play a role in the mode of action of ACTH; however, they do not appear to be obligatory intermediates in the steroidogenic process. The importance of calcium in regulating PG formation is discussed with special regard for the idea that this cation has a direct action on the enzyme systems which control PG synthesis.", "contents": "Further studies on the mechanisms controlling prostaglandin biosynthesis in the cat adrenal cortex: the role of calcium and cyclic AMP. In light of previous studies which have implicated prostaglandin (PG) formation as a link in ACTH-induced steroid production by isolated cat adrenocortical cells, experiments were carried out to provide additional information regarding the role of PGs in adrenal steroidogenesis and their interactions with calcium and cyclic AMP. Perfusion of cat adrenal glands with Locke's solution plus beta(1-24)-ACTH resulted in an immediate increase in PGF2alpha release, which rapidly declined to basal levels after the stimulus was withdrawn. In contrast, maximal rates of steroid release were manifest some 30 min after removal of ACTH. ACTH and its onitrophenyl sulfenyl derivative (NPS-ACTH) increased PG (PGF2alpha and PGE2) and steroid release by trypsin-dispersed cat cortical cells, but NPS-ACTH, unlike ACTH, did not augment cortical cyclic AMP levels. In this same preparation, indomethacin completely blocked ACTH and NPS-ACTH facilitated PGF2alpha and PGE2 release but failed to suppress steroid release markedly. Calcium-deprivation blocked PG and steroid release evoked by these two polypeptides, and depressed PG release elicited by monobutyryl cyclic AMP (bcAMP) without affecting steroid release. These experiments offer additional evidence to support the concept that PGs play a role in the mode of action of ACTH; however, they do not appear to be obligatory intermediates in the steroidogenic process. The importance of calcium in regulating PG formation is discussed with special regard for the idea that this cation has a direct action on the enzyme systems which control PG synthesis."}
{"id": "PMID:187410", "title": "The inhibitory effect of acute administration of excess iodide on the formation of adenosine 3', 5'-monophosphate induced by thyrotropin in mouse thyroid lobes.", "content": "In a previous paper, we demonstrated that an inhibitory action of excess iodide on thyrotropin-induced thyroid hormone secretion occurs at a site subsequent to the generation of cyclic AMP. In the present study, however, we have found that thyroidal cyclic AMP formation induced by thyrotropin in vitro was markedly inhibited by the acute administration of excess iodide to mice fed a low iodine diet. In contrast, excess iodide failed to produce inhibition in animals fed a regular diet. In vitro stimulation by long-acting thyroid stimulator (LATS), prostaglandin E2, and 4-methylhistamine of cyclic AMP formation in mouse thyroid lobes was also significantly inhibited by the acute in vivo administration of excess iodide. The inhibition was completely relieved by the administration of methimazole prior to excess iodide. Furthermore, it has been shown that thyroid adenylate cyclase activity induced by thyrotropin was markedly depressed by excess iodide under similar experimental conditions. Therefore, it is suggested that one of the inhibitory actions of excess iodide is on the adenylate cyclase-cyclic AMP system and further, that iodide can elicit its inhibitory action after its conversion to some form of organic iodine.", "contents": "The inhibitory effect of acute administration of excess iodide on the formation of adenosine 3', 5'-monophosphate induced by thyrotropin in mouse thyroid lobes. In a previous paper, we demonstrated that an inhibitory action of excess iodide on thyrotropin-induced thyroid hormone secretion occurs at a site subsequent to the generation of cyclic AMP. In the present study, however, we have found that thyroidal cyclic AMP formation induced by thyrotropin in vitro was markedly inhibited by the acute administration of excess iodide to mice fed a low iodine diet. In contrast, excess iodide failed to produce inhibition in animals fed a regular diet. In vitro stimulation by long-acting thyroid stimulator (LATS), prostaglandin E2, and 4-methylhistamine of cyclic AMP formation in mouse thyroid lobes was also significantly inhibited by the acute in vivo administration of excess iodide. The inhibition was completely relieved by the administration of methimazole prior to excess iodide. Furthermore, it has been shown that thyroid adenylate cyclase activity induced by thyrotropin was markedly depressed by excess iodide under similar experimental conditions. Therefore, it is suggested that one of the inhibitory actions of excess iodide is on the adenylate cyclase-cyclic AMP system and further, that iodide can elicit its inhibitory action after its conversion to some form of organic iodine."}
{"id": "PMID:187411", "title": "Effects of follicle stimulating hormone and luteinizing hormone upon cyclic AMP and cyclic GMP levels in rat ovaries in vitro.", "content": "In vitro effects of FSH and LH on adenosine 3',5'-cyclic monophosphate (cyclic AMP) and guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels in rat ovarian tissue were studied. Ovaries from immature rats treated with either pregnant mare's serum (PMS) or PMS and human chorionic gonadotropin (hCG) were incubated at 37 C for 30 min in defined medium 199 containing aminophylline (0.1 mg/ml). Increasing concentrations of LH (0.4-10.0 mug) when added to the medium containing ovaries with predominantly follicular tissue (PMS-treated) produced progressive increases in cyclic AMP (29-300%) and concomitant decreases in cyclic GMP (41-70%). FSH (4-100 mug) added to the medium produced comparable changes in nucleotide levels: cyclic AMP increased 52-390% and cyclic GMP decreased 45-80%. Ovaries with predominantly luteal tissue (PMS- and hCG-treated) responded differently to the same experimental conditions. LH produced a much greater increase in tissue cyclic AMP levels (209-1280%), whereas FSH produced comparable increases in cyclic AMP as seen with follicular tissue (103-570%). Neither gonadotropin caused any changes in cyclic GMP levels in luteinized ovaries. These results indicate that rat ovarian cyclic GMP is regulated by gonadotropins and the differences in the direction of nucleotide response to gonadotropins suggest divergent roles for cyclic AMP and cyclic GMP in ovarian function.", "contents": "Effects of follicle stimulating hormone and luteinizing hormone upon cyclic AMP and cyclic GMP levels in rat ovaries in vitro. In vitro effects of FSH and LH on adenosine 3',5'-cyclic monophosphate (cyclic AMP) and guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels in rat ovarian tissue were studied. Ovaries from immature rats treated with either pregnant mare's serum (PMS) or PMS and human chorionic gonadotropin (hCG) were incubated at 37 C for 30 min in defined medium 199 containing aminophylline (0.1 mg/ml). Increasing concentrations of LH (0.4-10.0 mug) when added to the medium containing ovaries with predominantly follicular tissue (PMS-treated) produced progressive increases in cyclic AMP (29-300%) and concomitant decreases in cyclic GMP (41-70%). FSH (4-100 mug) added to the medium produced comparable changes in nucleotide levels: cyclic AMP increased 52-390% and cyclic GMP decreased 45-80%. Ovaries with predominantly luteal tissue (PMS- and hCG-treated) responded differently to the same experimental conditions. LH produced a much greater increase in tissue cyclic AMP levels (209-1280%), whereas FSH produced comparable increases in cyclic AMP as seen with follicular tissue (103-570%). Neither gonadotropin caused any changes in cyclic GMP levels in luteinized ovaries. These results indicate that rat ovarian cyclic GMP is regulated by gonadotropins and the differences in the direction of nucleotide response to gonadotropins suggest divergent roles for cyclic AMP and cyclic GMP in ovarian function."}
{"id": "PMID:187412", "title": "Ovarian follicular development in the rat: hormone receptor regulation by estradiol, follicle stimulating hormone and luteinizing hormone.", "content": "The effects of estradiol, FSH and LH on ovarian follicular development and granulosa cell differentiation were examined in the immature rat hypophysectomized on day 24 of age. Administration of estradiol to hypophysectomized rats for 4 days stimulated the growth of large preantral follicles with a concomitant 1.5-fold increase in FSH receptor content and a 4-fold decrease in LH receptor content in the granulosa cells. When highly purified hFSH was administered alone, receptor content for FSH increased progressively for 4 days while receptor for LH remained essentially unchanged. However, when rats were pretreated with estradiol, the response of follicles to FSH was markedly enhanced as indicated by the appearance of large, antral follicles and elevated receptor content for both FSH and LH. Receptor content for FSH increased markedly in response to hFSH following only one day of estradiol pretreatment, while receptor content for LH increased most rapidly in response to hFSH after 3 days of estradiol pretreatment. LH administered to rats possessing large preovulatory follicles caused luteinization of granulosa cells and a marked decline in receptor content for both gonadotropins within 24 h. Receptor content remained low even 48 h after LH administration when granulosa cells were fully luteinized. These results indicated that follicular development and granulosa cell differentiation are dependent on steroid-protein hormone regulation of hormone specific receptors.", "contents": "Ovarian follicular development in the rat: hormone receptor regulation by estradiol, follicle stimulating hormone and luteinizing hormone. The effects of estradiol, FSH and LH on ovarian follicular development and granulosa cell differentiation were examined in the immature rat hypophysectomized on day 24 of age. Administration of estradiol to hypophysectomized rats for 4 days stimulated the growth of large preantral follicles with a concomitant 1.5-fold increase in FSH receptor content and a 4-fold decrease in LH receptor content in the granulosa cells. When highly purified hFSH was administered alone, receptor content for FSH increased progressively for 4 days while receptor for LH remained essentially unchanged. However, when rats were pretreated with estradiol, the response of follicles to FSH was markedly enhanced as indicated by the appearance of large, antral follicles and elevated receptor content for both FSH and LH. Receptor content for FSH increased markedly in response to hFSH following only one day of estradiol pretreatment, while receptor content for LH increased most rapidly in response to hFSH after 3 days of estradiol pretreatment. LH administered to rats possessing large preovulatory follicles caused luteinization of granulosa cells and a marked decline in receptor content for both gonadotropins within 24 h. Receptor content remained low even 48 h after LH administration when granulosa cells were fully luteinized. These results indicated that follicular development and granulosa cell differentiation are dependent on steroid-protein hormone regulation of hormone specific receptors."}
{"id": "PMID:187413", "title": "Luteal cell receptor content for prolactin (PRL) and luteinizing hormone (LH): regulation by LH and PRL.", "content": "The effect of LH and PRL during the differentiation of granulosa cells to luteal cells was examined by determining the ability of LH and PRL to regulate luteal cell receptor content for these hormones and to increase production of progesterone. Preovulatory follicles and corpora lutea were hormonally induced in immature hypophysectomized female rats by sequential treatment with estradiol, hFSH and oLH. The content of receptor for LH was high in granulosa cells of large antral follicles. Administration of LH caused receptor for LH to decrease markedly within 24 h and to remain low for 96 h. In contrast, granulosa cell content of receptor for PRL increased progressively for 48 h following LH stimulation and remained elevated in fully luteinized cells at 96 h. This increase in PRL receptor appears to be functionally related to the ability of luteal cells to respond to PRL. When PRL was given for 4 days after LH, both luteal cell progesterone production and LH receptor content increased progressively after, but not before, 48 h. Since these changes occurred in the absence of LH, the increase in LH receptor appears to be a consequence of, but not a requirement for, the PRL-induced increase in progesterone production. If daily injections of PRL were delayed for 72 or 96 h following LH induction of lutenization, luteolytic rather than luteotropic effects of PRL were observed. Since receptor for PRL remained elevated at 72 and 96 h, intracellular mechanisms and not receptor content, appear to be effecting the response of luteal cell to PRL.", "contents": "Luteal cell receptor content for prolactin (PRL) and luteinizing hormone (LH): regulation by LH and PRL. The effect of LH and PRL during the differentiation of granulosa cells to luteal cells was examined by determining the ability of LH and PRL to regulate luteal cell receptor content for these hormones and to increase production of progesterone. Preovulatory follicles and corpora lutea were hormonally induced in immature hypophysectomized female rats by sequential treatment with estradiol, hFSH and oLH. The content of receptor for LH was high in granulosa cells of large antral follicles. Administration of LH caused receptor for LH to decrease markedly within 24 h and to remain low for 96 h. In contrast, granulosa cell content of receptor for PRL increased progressively for 48 h following LH stimulation and remained elevated in fully luteinized cells at 96 h. This increase in PRL receptor appears to be functionally related to the ability of luteal cells to respond to PRL. When PRL was given for 4 days after LH, both luteal cell progesterone production and LH receptor content increased progressively after, but not before, 48 h. Since these changes occurred in the absence of LH, the increase in LH receptor appears to be a consequence of, but not a requirement for, the PRL-induced increase in progesterone production. If daily injections of PRL were delayed for 72 or 96 h following LH induction of lutenization, luteolytic rather than luteotropic effects of PRL were observed. Since receptor for PRL remained elevated at 72 and 96 h, intracellular mechanisms and not receptor content, appear to be effecting the response of luteal cell to PRL."}
{"id": "PMID:187414", "title": "Amino acid transport in follicles isolated from the rabbit ovary.", "content": "The model amino acid alpha-aminoisobutyric acid (AIB) has been used to investigate amino acid transport in follicles isolated from rabbit ovaries. LH markedly increased AIB transport, while incubation with FSH, cAMP or dbcAMP failed to increase the process. Several kinds of inhibitors have been utilized to characterize follicular AIB transport as an energy dependent process and apparently independent of follicular steroidogenesis. The rates of AIB efflux from preloaded follicles were measured in the presence and absence of LH; the rate measurements suggest that only the rate of entry of AIB into follicular cells is stimulated by the gonadotropin. Further experiments used inhibitors of RNA and protein synthesis to examine the relationship between AIB transport and the synthesis of macromolecules. Whereas blocking RNA synthesis suppressed the LH effect on AIB transport, inhibitors of protein synthesis increased the rate of AIB movement into follicles. The in vitro transport of AIB was also studied in follicles isolated 2 hr after mating and in ovulated follicles which were obtained 12 h after coitus. AIB transport rate showed a rise following mating but fell to less than precoital rates in ovulated (12 h) follicles. Transport in both 2 and 12 h follicles proved unresponsive to LH stimulation. Taken together, these studies suggest that AIB transport in isolated ovarian follicles is a LH-sensitive, energy-dependent process. Although AIB transport changes in a pattern qualitatively similar to that previously reported for postcoital protein synthesis, LH stimulation of the two processes may be via different mechanisms.", "contents": "Amino acid transport in follicles isolated from the rabbit ovary. The model amino acid alpha-aminoisobutyric acid (AIB) has been used to investigate amino acid transport in follicles isolated from rabbit ovaries. LH markedly increased AIB transport, while incubation with FSH, cAMP or dbcAMP failed to increase the process. Several kinds of inhibitors have been utilized to characterize follicular AIB transport as an energy dependent process and apparently independent of follicular steroidogenesis. The rates of AIB efflux from preloaded follicles were measured in the presence and absence of LH; the rate measurements suggest that only the rate of entry of AIB into follicular cells is stimulated by the gonadotropin. Further experiments used inhibitors of RNA and protein synthesis to examine the relationship between AIB transport and the synthesis of macromolecules. Whereas blocking RNA synthesis suppressed the LH effect on AIB transport, inhibitors of protein synthesis increased the rate of AIB movement into follicles. The in vitro transport of AIB was also studied in follicles isolated 2 hr after mating and in ovulated follicles which were obtained 12 h after coitus. AIB transport rate showed a rise following mating but fell to less than precoital rates in ovulated (12 h) follicles. Transport in both 2 and 12 h follicles proved unresponsive to LH stimulation. Taken together, these studies suggest that AIB transport in isolated ovarian follicles is a LH-sensitive, energy-dependent process. Although AIB transport changes in a pattern qualitatively similar to that previously reported for postcoital protein synthesis, LH stimulation of the two processes may be via different mechanisms."}
{"id": "PMID:187415", "title": "Dibutyryl cyclic AMP, adenosine and guanosine blockade of the dopamine, ergocryptine and apomorphine inhibition of prolactin release in vitro.", "content": "Rat anterior hemipituitaries were incubated in Krebs-Ringer bicarbonate containing [3H]leucine. Newly synthesized [3H]prolactin and [3H]GH in the pituitary and incubation medium were assayed, as was the radioimmunoassayable prolactin released into the medium during a 5-h incubation. Dopamine (7.5 X 10(-8)M), ergocryptine (4 X 10(-10) M) and apomorphine (6 X 10(-8)M) all significantly inhibited both radioimmunoassayable prolactin release and newly-labeled [3H]prolactin release without affecting [3H]GH release. Conversely, dibutyryl cyclic AMP (2.5 mM) stimulated radioimmunoassayable prolactin release as well as [3H]prolactin and [3H]GH release. The addition of 2.5 mM dibutyryl cyclic AMP to media containing dopamine, ergocryptine or apomorphine completely restored both radioimmunoassayable prolactin release and [3H]prolactin release to at least control levels. Dopamine, ergocryptine and apomorphine all inhibited incorporation of [3H]leucine into prolactin but not into GH, whereas 2.5 mM dibltyryl cyclic AMP with any one of the inhibitors restored total incorporation into [3H]prolactin to levels insignificantly lower than the nucleotide-stimulated incorporation. Adenosine and guanosine at 2.5 mM also stimulated incorporation into [3H]prolactin and blocked the inhibitory effects of apomorphine upon [3H]prolactin synthesis and release. These nucleosides also stimulated [3H]GH release; and guanosine, but not adenosine, stimulated incorporation into [3H]GH. The ability of dibutryl  cyclic AMP to block the effects of dopamine, ergocryptine and apomorphine upon prolactin release is consistent with these three inhibitors acting by a common mechanism. Cyclic AMP could be hypothesized as a second messenger for prolactin release, but the ability of adenosine and guanosine to mimic almost perfectly the effects of this cyclic nucleotide does not allow any conclusive interpretation.", "contents": "Dibutyryl cyclic AMP, adenosine and guanosine blockade of the dopamine, ergocryptine and apomorphine inhibition of prolactin release in vitro. Rat anterior hemipituitaries were incubated in Krebs-Ringer bicarbonate containing [3H]leucine. Newly synthesized [3H]prolactin and [3H]GH in the pituitary and incubation medium were assayed, as was the radioimmunoassayable prolactin released into the medium during a 5-h incubation. Dopamine (7.5 X 10(-8)M), ergocryptine (4 X 10(-10) M) and apomorphine (6 X 10(-8)M) all significantly inhibited both radioimmunoassayable prolactin release and newly-labeled [3H]prolactin release without affecting [3H]GH release. Conversely, dibutyryl cyclic AMP (2.5 mM) stimulated radioimmunoassayable prolactin release as well as [3H]prolactin and [3H]GH release. The addition of 2.5 mM dibutyryl cyclic AMP to media containing dopamine, ergocryptine or apomorphine completely restored both radioimmunoassayable prolactin release and [3H]prolactin release to at least control levels. Dopamine, ergocryptine and apomorphine all inhibited incorporation of [3H]leucine into prolactin but not into GH, whereas 2.5 mM dibltyryl cyclic AMP with any one of the inhibitors restored total incorporation into [3H]prolactin to levels insignificantly lower than the nucleotide-stimulated incorporation. Adenosine and guanosine at 2.5 mM also stimulated incorporation into [3H]prolactin and blocked the inhibitory effects of apomorphine upon [3H]prolactin synthesis and release. These nucleosides also stimulated [3H]GH release; and guanosine, but not adenosine, stimulated incorporation into [3H]GH. The ability of dibutryl  cyclic AMP to block the effects of dopamine, ergocryptine and apomorphine upon prolactin release is consistent with these three inhibitors acting by a common mechanism. Cyclic AMP could be hypothesized as a second messenger for prolactin release, but the ability of adenosine and guanosine to mimic almost perfectly the effects of this cyclic nucleotide does not allow any conclusive interpretation."}
{"id": "PMID:187416", "title": "Strain-dependent gonadal effects upon the response of adrenal cholesterol esters to ACTH in C57BL/10J and DBA/2J mice.", "content": "The response of adrenal cholesterol esters to ACTH administered in vivo was studied in males, females and male castrates of the C57BL)10J and DBA/21 strains of mice. The cholesterol ester fatty acids were transmethylated and analyzed by gas-liquid chromatography. There are sex and strain differences in the response of the adrenal cholesterol esters to ACTH. Neither the male nor the female C57 mouse shows a significant depletion of total cholesterol esters upon ACTH treatment. This result argues against the utilization of adrenal cholesterol esters for corticosteroid synthesis in this strain. In the female DBA mouse cholesterol ester depletion in response to ACTH is maximal. Neither the total cholesterol ester concentration nor the concentration of any individual ester is correlated with the pattern of response of the cholesterol esters to ACTH. Among the individual cholesterol esters, cholesteryl arachidonate (C20:4) is preferentially utilized after ACTH treatment in all groups except the C57 males. In contrast, cholesteryl adrenate (C22:4), which is generally the most abundant cholesterol ester, is conserved during ACTH stimulation in all groups except the DBA females. A cyclic interconversion between adrenate and arachidonate may be physiologically important in the control of adrenal function.", "contents": "Strain-dependent gonadal effects upon the response of adrenal cholesterol esters to ACTH in C57BL/10J and DBA/2J mice. The response of adrenal cholesterol esters to ACTH administered in vivo was studied in males, females and male castrates of the C57BL)10J and DBA/21 strains of mice. The cholesterol ester fatty acids were transmethylated and analyzed by gas-liquid chromatography. There are sex and strain differences in the response of the adrenal cholesterol esters to ACTH. Neither the male nor the female C57 mouse shows a significant depletion of total cholesterol esters upon ACTH treatment. This result argues against the utilization of adrenal cholesterol esters for corticosteroid synthesis in this strain. In the female DBA mouse cholesterol ester depletion in response to ACTH is maximal. Neither the total cholesterol ester concentration nor the concentration of any individual ester is correlated with the pattern of response of the cholesterol esters to ACTH. Among the individual cholesterol esters, cholesteryl arachidonate (C20:4) is preferentially utilized after ACTH treatment in all groups except the C57 males. In contrast, cholesteryl adrenate (C22:4), which is generally the most abundant cholesterol ester, is conserved during ACTH stimulation in all groups except the DBA females. A cyclic interconversion between adrenate and arachidonate may be physiologically important in the control of adrenal function."}
{"id": "PMID:187417", "title": "Somatostatin inhibits the release of acetylcholine induced electrically in the myenteric plexus.", "content": "Somatostatin inhibits the release of acetylcholine electrically induced in the myenteric plexus-longitudinal muscle of the guinea pig ileum. This effect is not mediated by opiate receptors. Tachyphylaxis to this effect of somatostatin has been observed.", "contents": "Somatostatin inhibits the release of acetylcholine induced electrically in the myenteric plexus. Somatostatin inhibits the release of acetylcholine electrically induced in the myenteric plexus-longitudinal muscle of the guinea pig ileum. This effect is not mediated by opiate receptors. Tachyphylaxis to this effect of somatostatin has been observed."}
{"id": "PMID:187418", "title": "Effect of heparin and adrenocorticotropin on the hepatic and serum cholesterol in catfish, Heteropneustes fossils.", "content": "The administration of heparin with or without ACTH significantly decreased hepatic cholesterol content in catfish. In serum, heparin alone produced first hypercholesterolemia which was followed by hypocholesterolemia whereas it potentiated hypercholesterolemic action of ACTH three hours after administration. It is concluded that heparin normally caused hypercholesterolemia by releasing cholesterol from liver as lipoprotein complex. The hypocholesterolemic action of heparin might be an indirect one.", "contents": "Effect of heparin and adrenocorticotropin on the hepatic and serum cholesterol in catfish, Heteropneustes fossils. The administration of heparin with or without ACTH significantly decreased hepatic cholesterol content in catfish. In serum, heparin alone produced first hypercholesterolemia which was followed by hypocholesterolemia whereas it potentiated hypercholesterolemic action of ACTH three hours after administration. It is concluded that heparin normally caused hypercholesterolemia by releasing cholesterol from liver as lipoprotein complex. The hypocholesterolemic action of heparin might be an indirect one."}
{"id": "PMID:187419", "title": "Effect of ACTH and its fragment on brain catecholamines in intact and adrenalectomized rats.", "content": "Brain catecholamine metabolism was monitored by distribution of labelled noradrenaline (3H-NA) after intraventricular injection to intact and adrenalectomized rats. The adrenalectomy produced an increased disappearance rate of the labelled pool in the hypothalamus, hippocampus and neocortex. These changes could be prevented by hydrocortisone pretreatment. Painful stimuli resulted in an increased disappearance of the labelled pool in both intact and adrenalectomized rats. The implantation of hydrocortisone into the tuberoinfundibular region prevented the stress-induced changes of the catecholamine metabolism. Intraventricular administration of ACTH1-24 and ACTH4-10 produced a significant increase of the disappearance rate in different brain regions of adrenalectomized rats. The blocking of catecholamine synthesis by intraventricular injection of alpha-methyl-m-tyrosine resulted in a marked decrease of the labelled pool but did not prevent the ACTH-induced decrease of the tracer pool. On the other hand, the blocking of monoamine-oxydase activity by Pargyline led to a marked increase of the labelled pool but intraventricular administration of ACTH led to an increase of the disappearance rate. The mechanism of ACTH action on brain catecholamine metabolism is still obscure, however, an increased release of the NA to ACTH peptides is very likely in the light of the present observations.", "contents": "Effect of ACTH and its fragment on brain catecholamines in intact and adrenalectomized rats. Brain catecholamine metabolism was monitored by distribution of labelled noradrenaline (3H-NA) after intraventricular injection to intact and adrenalectomized rats. The adrenalectomy produced an increased disappearance rate of the labelled pool in the hypothalamus, hippocampus and neocortex. These changes could be prevented by hydrocortisone pretreatment. Painful stimuli resulted in an increased disappearance of the labelled pool in both intact and adrenalectomized rats. The implantation of hydrocortisone into the tuberoinfundibular region prevented the stress-induced changes of the catecholamine metabolism. Intraventricular administration of ACTH1-24 and ACTH4-10 produced a significant increase of the disappearance rate in different brain regions of adrenalectomized rats. The blocking of catecholamine synthesis by intraventricular injection of alpha-methyl-m-tyrosine resulted in a marked decrease of the labelled pool but did not prevent the ACTH-induced decrease of the tracer pool. On the other hand, the blocking of monoamine-oxydase activity by Pargyline led to a marked increase of the labelled pool but intraventricular administration of ACTH led to an increase of the disappearance rate. The mechanism of ACTH action on brain catecholamine metabolism is still obscure, however, an increased release of the NA to ACTH peptides is very likely in the light of the present observations."}
{"id": "PMID:187420", "title": "The effect of maternal and fetal corticosteroids on the development of function of the pituitary-adrenocortical system.", "content": "The pituitary-adrenocortical system of rat fetuses was stimulated (larger adrenals at birth) by maternal adrenalectomy, or suppressed (smaller adrenals at birth) by implantation of an ACTH secreting pituitary tumor (MtTF4). Offspring were delivered by caesarean section and fostered to untreated females. Offspring of intact females delivered by caesarean section and normally delivered offspring of intact mothers both fostered to untreated lactating females served as controls. Body growth in the first three weeks of life was delayed in offspring of tumor bearing mothers in Control-fostered subjects as compared to the 2 other groups. At 70 days of age female offspring of the tumor implanted and adrenalectomized mothers, as well as the Control-caesarean females, had smaller adrenals than Control-fostered animals of the same sex. The adrenal size of males was not significantly affected. No significant differences were found in resting concentrations of corticosterone in plasma, although offspring of adrenalectomized mothers had high values. Suppressed adrenal response to ether stress was found in offspring of tumor bearing mothers. The supposition is that interference with maternal pituitary-adrenocortical activity during pregnancy has a long lasting effect on fetal hypothalamo-pituitary-adrenocortical system.", "contents": "The effect of maternal and fetal corticosteroids on the development of function of the pituitary-adrenocortical system. The pituitary-adrenocortical system of rat fetuses was stimulated (larger adrenals at birth) by maternal adrenalectomy, or suppressed (smaller adrenals at birth) by implantation of an ACTH secreting pituitary tumor (MtTF4). Offspring were delivered by caesarean section and fostered to untreated females. Offspring of intact females delivered by caesarean section and normally delivered offspring of intact mothers both fostered to untreated lactating females served as controls. Body growth in the first three weeks of life was delayed in offspring of tumor bearing mothers in Control-fostered subjects as compared to the 2 other groups. At 70 days of age female offspring of the tumor implanted and adrenalectomized mothers, as well as the Control-caesarean females, had smaller adrenals than Control-fostered animals of the same sex. The adrenal size of males was not significantly affected. No significant differences were found in resting concentrations of corticosterone in plasma, although offspring of adrenalectomized mothers had high values. Suppressed adrenal response to ether stress was found in offspring of tumor bearing mothers. The supposition is that interference with maternal pituitary-adrenocortical activity during pregnancy has a long lasting effect on fetal hypothalamo-pituitary-adrenocortical system."}
{"id": "PMID:187421", "title": "4-14C-progesterone conversion by the fetal rat adrenal gland in vitro.", "content": "The adrenal glands of rat fetuses with activated or inhibited pituitary adrenocorticotropic activity between the 15th and 22nd day of intrauterine development were incubated with 4-14C-progesterone for 3hr. Fetuses of intact mothers were used as controls. Conversion of progesterone into adrenal steroids was found increased on the 18th day of intrauterine development, i.e., at the time when fetal adrenocorticotropic activity begins. In comparison to controls, conversion of progesterone into fetal adrenal corticosteroids was the smallest in the fetuses of mothers with inhibited pituitary ACTH and the greatest in the adrenals of fetuses of mothers with activated pituitary adrenocorticotropic activity.", "contents": "4-14C-progesterone conversion by the fetal rat adrenal gland in vitro. The adrenal glands of rat fetuses with activated or inhibited pituitary adrenocorticotropic activity between the 15th and 22nd day of intrauterine development were incubated with 4-14C-progesterone for 3hr. Fetuses of intact mothers were used as controls. Conversion of progesterone into adrenal steroids was found increased on the 18th day of intrauterine development, i.e., at the time when fetal adrenocorticotropic activity begins. In comparison to controls, conversion of progesterone into fetal adrenal corticosteroids was the smallest in the fetuses of mothers with inhibited pituitary ACTH and the greatest in the adrenals of fetuses of mothers with activated pituitary adrenocorticotropic activity."}
{"id": "PMID:187424", "title": "Specific and nonspecific multiple unit activities during the onset of pentylenetetrazol seizures. II. Acute lesions interrupting nonspecific system connections.", "content": "Nonspecific cortical, thalamic, mesencephalic, and pontine multiple unit activities (MUA) and changes in EEG and MUS of the sciatic nerve after threshold pentylenetetrazol activation were studied in three groups of animals in which neuronal connections were interrupted at three different levels of the central nervous system: spinal, mesencephalic, and prethalamic. Maximal increments of nonspecific MUA and maximal increments and maximal decrements of sciatic MUA after pentylenetetrazol from each group of lesioned animals were statistically compared with tose observed in intact animals. 1. Pentylenetetrazol threshold for producing cortical tonic-clonic EEG discharges was increased in animals with nesencephaic and prethalamic lesions but was not modified in animals with spinal transection. 2. Cortical MUA maximal increment was significantly decreased in mesencephalic and prethalamic lesioned animals, whereas thalamic MUA maximal increment was significantly decreased in mesencephalic and significantly increased in prethalamic lesioned animals. Pontine MUA maximal increment was significantly increased in spinal, mesencephalic, and prethalamic lesioned animals, and mesencephalic M-A maximal increment was not significantly modified in either prethalamic lesioned or in spinal transected animals. 3. Sciatic MUA maximal increment and maximal decrement were significatly decreased in spinal transected animals, whereas only maximal increment was significantly decreased in mesencephalic and only maximal decrement was significantly decreased in prethalamic lesioned animals. These results based on lesion experiments permit us to infer than under normal cinditions the development of generalized seizures induced by threshold pentylenetetrazol injection is highly dependent upon the neuronal interactions between nonspecific structures at different levels of the central nervous system. The possible nature of these neuronal interactions in the intact animals is discussed.", "contents": "Specific and nonspecific multiple unit activities during the onset of pentylenetetrazol seizures. II. Acute lesions interrupting nonspecific system connections. Nonspecific cortical, thalamic, mesencephalic, and pontine multiple unit activities (MUA) and changes in EEG and MUS of the sciatic nerve after threshold pentylenetetrazol activation were studied in three groups of animals in which neuronal connections were interrupted at three different levels of the central nervous system: spinal, mesencephalic, and prethalamic. Maximal increments of nonspecific MUA and maximal increments and maximal decrements of sciatic MUA after pentylenetetrazol from each group of lesioned animals were statistically compared with tose observed in intact animals. 1. Pentylenetetrazol threshold for producing cortical tonic-clonic EEG discharges was increased in animals with nesencephaic and prethalamic lesions but was not modified in animals with spinal transection. 2. Cortical MUA maximal increment was significantly decreased in mesencephalic and prethalamic lesioned animals, whereas thalamic MUA maximal increment was significantly decreased in mesencephalic and significantly increased in prethalamic lesioned animals. Pontine MUA maximal increment was significantly increased in spinal, mesencephalic, and prethalamic lesioned animals, and mesencephalic M-A maximal increment was not significantly modified in either prethalamic lesioned or in spinal transected animals. 3. Sciatic MUA maximal increment and maximal decrement were significatly decreased in spinal transected animals, whereas only maximal increment was significantly decreased in mesencephalic and only maximal decrement was significantly decreased in prethalamic lesioned animals. These results based on lesion experiments permit us to infer than under normal cinditions the development of generalized seizures induced by threshold pentylenetetrazol injection is highly dependent upon the neuronal interactions between nonspecific structures at different levels of the central nervous system. The possible nature of these neuronal interactions in the intact animals is discussed."}
{"id": "PMID:187426", "title": "Alpha and beta adrenergic sensitivity in trained and untrained albino rats.", "content": "The effects on the blood pressure and heart rate responses of different adrenergic stimulants (norepinephrine, sympathomim, epinephrine and isoproterenol) and blocking agents (phenoxybenzamine and propranolol) were studied in control (N=55) and exercising (N=52) albino rats under anaesthesia. The test rats exercised by regular swimming for 10-14 weeks. Alpha stimulation and beta blocking produced smaller responses while alpha blocking and beta stimulation were followed by greater changes after training as compared with the control animals. The assumption of a modified adrenergic receptor sensitivity could not be substantiated by the results; the observations indicate rather a complex change in the autonomous regulation following regular physical exercise.", "contents": "Alpha and beta adrenergic sensitivity in trained and untrained albino rats. The effects on the blood pressure and heart rate responses of different adrenergic stimulants (norepinephrine, sympathomim, epinephrine and isoproterenol) and blocking agents (phenoxybenzamine and propranolol) were studied in control (N=55) and exercising (N=52) albino rats under anaesthesia. The test rats exercised by regular swimming for 10-14 weeks. Alpha stimulation and beta blocking produced smaller responses while alpha blocking and beta stimulation were followed by greater changes after training as compared with the control animals. The assumption of a modified adrenergic receptor sensitivity could not be substantiated by the results; the observations indicate rather a complex change in the autonomous regulation following regular physical exercise."}
{"id": "PMID:187427", "title": "Myocardial scintigraphy with 99mTc-pyrophosphate in 150 coronary care unit patients.", "content": "150 patients, admitted to the coronary care unit with suspicion of acute myocardial infarction, received pyrophosphate labelled with 99mTc, 6-120 h after onset of symptoms, mean 24 h, and were examined in the anterior posterior position and in the left anterior oblique position with a mobile gamma camera. Scintigrams were obtained initially at the injection, and then every 15th min during 1h. The scintigrams were evaluated with regard to presence and localization of radionuclide uptake in myocardial area. In 98 patients with a clinical diagnosis of acute myocardial infarction, uptake was found in 95, with good correlation between ECG and scintigraphic localization. 2. patients with myocardial infarction, verified at autopsy, did not show any uptake and 1 patient, surviving the myocardial infarction, also showed negative result. 19 of 26 patients with unstable angina pectoris also exhibited an uptake in the myocardium. 25 of 26 patients with other diagnoses showed no uptake, while in 1 patient an uptake was recorded. It is concluded that with 99mTc-pyrophosphate scintigraphy it is possible to separate ischemic heart disease from other diseases in patients with chest pain.", "contents": "Myocardial scintigraphy with 99mTc-pyrophosphate in 150 coronary care unit patients. 150 patients, admitted to the coronary care unit with suspicion of acute myocardial infarction, received pyrophosphate labelled with 99mTc, 6-120 h after onset of symptoms, mean 24 h, and were examined in the anterior posterior position and in the left anterior oblique position with a mobile gamma camera. Scintigrams were obtained initially at the injection, and then every 15th min during 1h. The scintigrams were evaluated with regard to presence and localization of radionuclide uptake in myocardial area. In 98 patients with a clinical diagnosis of acute myocardial infarction, uptake was found in 95, with good correlation between ECG and scintigraphic localization. 2. patients with myocardial infarction, verified at autopsy, did not show any uptake and 1 patient, surviving the myocardial infarction, also showed negative result. 19 of 26 patients with unstable angina pectoris also exhibited an uptake in the myocardium. 25 of 26 patients with other diagnoses showed no uptake, while in 1 patient an uptake was recorded. It is concluded that with 99mTc-pyrophosphate scintigraphy it is possible to separate ischemic heart disease from other diseases in patients with chest pain."}
{"id": "PMID:187428", "title": "Hyperlipoproteinemia in angiographically documented coronary artery disease.", "content": "Plasma lipids and lipoprotein levels were measured in 100 patients who underwent coronary angiography for chest pains. The coronary arteries were normal in 33 patients (22 males and 11 females), moderately pathological (30--60% narrowing) in 4, and markedly pathological (greater than 60% narrowing) in 63 (53 males and 10 females). Plasma cholesterol and triglyceride levels and very low and low density lipoprotein cholesterol levels were higher by 20--40% in both males and females with pathological coronary arteries as compared to normals. The high density plasma lipoprotein cholesterol level was lower in females with pathological arteries than in normals, but did not differ between the male groups. 67% of the males with pathological arteries had hyperlipoproteinemia as compared to 26% of the normals, and hyperlipoproteinemia was as frequent among males emigrating to Isreal from Europe or America as among those born in Asia or Africa. Hyperlipoproteinemia types IIA, IIB and IV were encountered among the patients at similar rates.", "contents": "Hyperlipoproteinemia in angiographically documented coronary artery disease. Plasma lipids and lipoprotein levels were measured in 100 patients who underwent coronary angiography for chest pains. The coronary arteries were normal in 33 patients (22 males and 11 females), moderately pathological (30--60% narrowing) in 4, and markedly pathological (greater than 60% narrowing) in 63 (53 males and 10 females). Plasma cholesterol and triglyceride levels and very low and low density lipoprotein cholesterol levels were higher by 20--40% in both males and females with pathological coronary arteries as compared to normals. The high density plasma lipoprotein cholesterol level was lower in females with pathological arteries than in normals, but did not differ between the male groups. 67% of the males with pathological arteries had hyperlipoproteinemia as compared to 26% of the normals, and hyperlipoproteinemia was as frequent among males emigrating to Isreal from Europe or America as among those born in Asia or Africa. Hyperlipoproteinemia types IIA, IIB and IV were encountered among the patients at similar rates."}
{"id": "PMID:187429", "title": "Antigenic specificity of the cytolytic T lymphocyte (CTL) response to murine sarcoma virus-induced tumors. I. Preferential reactivity of in vitro generated secondary CTL with syngeneic tumor cells.", "content": "Incubation of spleen cells from mice having rejected a Moloney sarcoma virus (MSV)-induced tumor with syngeneic irradiated lymphoma or sarcoma cells bearing MSV-associated antigens in secondary mixed leukocyte-tumor cell cultures (MLTC) resulted in the generation of highly active cytolytic T lymphocytes (CTL) specifically directed against syngeneic target cells bearing MSV-associated antigens. When MSV-immune spleen cells from C57BL/6 (H-2b) and BALB/c(H-2d) mice were compared with respect to their ability to generate CTL in syngeneic secondary MLTC, it was found that both lymphoid cell populations were equally able to mount an anamnestic CTL response to MSV-associated antigens as assessed by a short-term 21Cr release assay. However, quantitative analysis of the activity of both CTL populations on either H-2b or H-2d tumor cells indicated that target cells sharing the same major histocompatibility complex (MHC) as the effector cells were lysed 10- to 100-fold more efficiently than allogeneic target cells. As suggested by the results of inhibition experiments using mixtures of 51Cr-labeled and unlabeled target cells, preferential lysis of syngeneic versus allogeneic tumor cells might be related to the establishment of effective adhesions between the former and CTL. Direct evidence for the role of MHC in determining the antigenic specificity of CTL directed against MSV-associated antigens was provided by results obtained using MSV-immune spleen cells from congenic resistant mice. Furthermore, studies of the response of F1 (H-2b/d) hybrid mice showed that stimulation of immune spleen cells with tumor cells from one parental strain or the other in secondary MLTC resulted in the generation of CTL capable of lysing tumor target cells of the same perental strain as the stimulating cells, but not of the other. The results thus suggested the presence of two sets of CTL precursor cells in F1 MSV-immune spleens, each set responding exclusively to tumor antigens associated with only one of the two parental phenotypes.", "contents": "Antigenic specificity of the cytolytic T lymphocyte (CTL) response to murine sarcoma virus-induced tumors. I. Preferential reactivity of in vitro generated secondary CTL with syngeneic tumor cells. Incubation of spleen cells from mice having rejected a Moloney sarcoma virus (MSV)-induced tumor with syngeneic irradiated lymphoma or sarcoma cells bearing MSV-associated antigens in secondary mixed leukocyte-tumor cell cultures (MLTC) resulted in the generation of highly active cytolytic T lymphocytes (CTL) specifically directed against syngeneic target cells bearing MSV-associated antigens. When MSV-immune spleen cells from C57BL/6 (H-2b) and BALB/c(H-2d) mice were compared with respect to their ability to generate CTL in syngeneic secondary MLTC, it was found that both lymphoid cell populations were equally able to mount an anamnestic CTL response to MSV-associated antigens as assessed by a short-term 21Cr release assay. However, quantitative analysis of the activity of both CTL populations on either H-2b or H-2d tumor cells indicated that target cells sharing the same major histocompatibility complex (MHC) as the effector cells were lysed 10- to 100-fold more efficiently than allogeneic target cells. As suggested by the results of inhibition experiments using mixtures of 51Cr-labeled and unlabeled target cells, preferential lysis of syngeneic versus allogeneic tumor cells might be related to the establishment of effective adhesions between the former and CTL. Direct evidence for the role of MHC in determining the antigenic specificity of CTL directed against MSV-associated antigens was provided by results obtained using MSV-immune spleen cells from congenic resistant mice. Furthermore, studies of the response of F1 (H-2b/d) hybrid mice showed that stimulation of immune spleen cells with tumor cells from one parental strain or the other in secondary MLTC resulted in the generation of CTL capable of lysing tumor target cells of the same perental strain as the stimulating cells, but not of the other. The results thus suggested the presence of two sets of CTL precursor cells in F1 MSV-immune spleens, each set responding exclusively to tumor antigens associated with only one of the two parental phenotypes."}
{"id": "PMID:187430", "title": "Differences in effect of isoproterenol stimulation on levels of cyclic AMP in human B and T lymphocytes.", "content": "The level of cyclic AMP (cAMP) in human lymphocytes in the presence or absence of isoproterenol stimulation was studied in various lymphocyte subpopulations containing different proportions of B and T lymphocytes. Lymphocytes from thymus and peripheral blood (which contain a majority of T cells) were more sensitive to isoproterenol action than lymphocytes from tonsils or adenoids (where B cells are predominant). Using purified B or T lymphocytes from peripheral blood, tonsils or adenoids, we observed an absence of B lymphocyte response to isoproterenol, whereas T lymphocytes, which had a lower basal c-AMP level than B cells, exhibited in all experiments a significant increase in cAMP content after isoproterenol stimulation. The intensity of the response varied in the different T lymphocyte subpopulations.", "contents": "Differences in effect of isoproterenol stimulation on levels of cyclic AMP in human B and T lymphocytes. The level of cyclic AMP (cAMP) in human lymphocytes in the presence or absence of isoproterenol stimulation was studied in various lymphocyte subpopulations containing different proportions of B and T lymphocytes. Lymphocytes from thymus and peripheral blood (which contain a majority of T cells) were more sensitive to isoproterenol action than lymphocytes from tonsils or adenoids (where B cells are predominant). Using purified B or T lymphocytes from peripheral blood, tonsils or adenoids, we observed an absence of B lymphocyte response to isoproterenol, whereas T lymphocytes, which had a lower basal c-AMP level than B cells, exhibited in all experiments a significant increase in cAMP content after isoproterenol stimulation. The intensity of the response varied in the different T lymphocyte subpopulations."}
{"id": "PMID:187431", "title": "Identification of murine leukemia viral antigens detected on mouse cells by H-2 alloantisera.", "content": "H-2 alloantisera have been previously reported to contain antibodies against murine leukemia viral antigens, but the nature of the viral antigens on mouse cells which interact with these antibodies has not been established. We have found that H-2 alloantisera recognize components of molecular weight 70 000-80 000 mouse lymphocytes and leukemia cells. These components were also detected by a goat antiserum against the murine leukemia virus (MuLV) glycoprotein (gp 70) and are therefore closely related to or identical with that viral protein. Although most H-2 alloantisera detected gp 70-like molecules  on lymphocytes and leukemia cells from a great variety of mouse strains, only one H-2 alloantiserum was found to interact with a gp 70 component on cells from C57BL/10 and C57BL/6 mice. Animals such as C57BL/10 mice that lacked the component reacting with most H-2 alloantisera showed increased serum levels of anti-MuLV antibodies after injection of B10.A spleen cells having a gp 70 component detectable by other H-2 alloantisera. In contrast, strains with cells reactive to antiviral antibodies in the H-2 alloantisera had low responses to MuLV antigens after a similar immunization procedure. Serum levels of anti-MuLV antibodies in both groups of mice, however, were increased after injection of Freund's adjuvant. These observations suggest that anti-MuLV antibodies in mouse alloantisera may arise from a response to viral antigens on the immunizing cells and general stimulation of the immune system.", "contents": "Identification of murine leukemia viral antigens detected on mouse cells by H-2 alloantisera. H-2 alloantisera have been previously reported to contain antibodies against murine leukemia viral antigens, but the nature of the viral antigens on mouse cells which interact with these antibodies has not been established. We have found that H-2 alloantisera recognize components of molecular weight 70 000-80 000 mouse lymphocytes and leukemia cells. These components were also detected by a goat antiserum against the murine leukemia virus (MuLV) glycoprotein (gp 70) and are therefore closely related to or identical with that viral protein. Although most H-2 alloantisera detected gp 70-like molecules  on lymphocytes and leukemia cells from a great variety of mouse strains, only one H-2 alloantiserum was found to interact with a gp 70 component on cells from C57BL/10 and C57BL/6 mice. Animals such as C57BL/10 mice that lacked the component reacting with most H-2 alloantisera showed increased serum levels of anti-MuLV antibodies after injection of B10.A spleen cells having a gp 70 component detectable by other H-2 alloantisera. In contrast, strains with cells reactive to antiviral antibodies in the H-2 alloantisera had low responses to MuLV antigens after a similar immunization procedure. Serum levels of anti-MuLV antibodies in both groups of mice, however, were increased after injection of Freund's adjuvant. These observations suggest that anti-MuLV antibodies in mouse alloantisera may arise from a response to viral antigens on the immunizing cells and general stimulation of the immune system."}
{"id": "PMID:187432", "title": "Interference of inhibitors of dopamine-beta-hydroxylase with uptake of monoamines by chromaffin granular membranes.", "content": "Disulfiram and bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulphide (FLA 63) markedly inhibited the Mg2+/ATP-dependent uptake of various monoamines, e.g. dopamine (DA), by isolated membranes of bovine adrenal chromaffin granules. Both compounds affected DA-beta-hydroxylase (DBH) activity more markedly than the uptake of DA. Other inhibitors of DBH, e.g. fusaric acid and diethyldithiocarbaminate (DDC), did not interfere with DA uptake. Disulfiram and FLA 63, in contrast to fusaric acid and DDC, also caused a partial inhibition of Mg2+-dependent ATPase. It is concluded that the inhibition of monoamine uptake by disulfiram and FLA 63 is not related to their effect on DBH.", "contents": "Interference of inhibitors of dopamine-beta-hydroxylase with uptake of monoamines by chromaffin granular membranes. Disulfiram and bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulphide (FLA 63) markedly inhibited the Mg2+/ATP-dependent uptake of various monoamines, e.g. dopamine (DA), by isolated membranes of bovine adrenal chromaffin granules. Both compounds affected DA-beta-hydroxylase (DBH) activity more markedly than the uptake of DA. Other inhibitors of DBH, e.g. fusaric acid and diethyldithiocarbaminate (DDC), did not interfere with DA uptake. Disulfiram and FLA 63, in contrast to fusaric acid and DDC, also caused a partial inhibition of Mg2+-dependent ATPase. It is concluded that the inhibition of monoamine uptake by disulfiram and FLA 63 is not related to their effect on DBH."}
{"id": "PMID:187433", "title": "The effect of adrenergic agonists and cyclic AMP on the Na+/K+ ATPase activity of brown adipose tissue.", "content": "The Na+/K+ ATPase activity of membrane fractions prepared from brown adipose tissue of cold-acclimated rats could be stimulated by addition of any one of the following: norepinephrine, isoproterenol, cyclic AMP or phenylephrine. These results are consistent with the proposal that in the intact brown adipocyte, the norepinephrine-induced stimulation of the Na+/K+ membrane pump is associated with alpha- as well as beta-adrenergic pathways and is, in part, mediated via cyclic AMP.", "contents": "The effect of adrenergic agonists and cyclic AMP on the Na+/K+ ATPase activity of brown adipose tissue. The Na+/K+ ATPase activity of membrane fractions prepared from brown adipose tissue of cold-acclimated rats could be stimulated by addition of any one of the following: norepinephrine, isoproterenol, cyclic AMP or phenylephrine. These results are consistent with the proposal that in the intact brown adipocyte, the norepinephrine-induced stimulation of the Na+/K+ membrane pump is associated with alpha- as well as beta-adrenergic pathways and is, in part, mediated via cyclic AMP."}
{"id": "PMID:187434", "title": "The role of prostaglandins in cholinergic neurotransmission in the guinea pig.", "content": "Prostaglandins have contrasting effects on neurotransmission at different cholinergic nerve endings. This is a report on the role of prostaglandins in a number of cholinergic preparations from the guinea pig. In the isolated ileum PGE1 (2 X 10(-10) to 5 X 10(-8) M) potentiated the response to electrical stimulation of the cholinergic nerves. PGE1 (10(-7 M) caused an increase in tone followed by a period of transient inhibition of twitch height. Responses to simulation of the ileum with drugs were not potentiated by PGE1. Responses of atropinized or plexus-free muscle to electrical stimulation were also not potentiated by PGE1. Acetylsalicylic acid (2.5 X 10(-4) M) diminished the twitch response and the output of acetylcholine from the ileum. Both effects were reversed by PGE1. Qualitatively similar observations were made on the trachea. It is concluded that prostaglandins facilitate acetylcholine release in the ileum and trachea. PGE1 diminished the effect of vagal stimulation on the heart rate. The response to stimulation of the phrenic nerve was not affected.", "contents": "The role of prostaglandins in cholinergic neurotransmission in the guinea pig. Prostaglandins have contrasting effects on neurotransmission at different cholinergic nerve endings. This is a report on the role of prostaglandins in a number of cholinergic preparations from the guinea pig. In the isolated ileum PGE1 (2 X 10(-10) to 5 X 10(-8) M) potentiated the response to electrical stimulation of the cholinergic nerves. PGE1 (10(-7 M) caused an increase in tone followed by a period of transient inhibition of twitch height. Responses to simulation of the ileum with drugs were not potentiated by PGE1. Responses of atropinized or plexus-free muscle to electrical stimulation were also not potentiated by PGE1. Acetylsalicylic acid (2.5 X 10(-4) M) diminished the twitch response and the output of acetylcholine from the ileum. Both effects were reversed by PGE1. Qualitatively similar observations were made on the trachea. It is concluded that prostaglandins facilitate acetylcholine release in the ileum and trachea. PGE1 diminished the effect of vagal stimulation on the heart rate. The response to stimulation of the phrenic nerve was not affected."}
{"id": "PMID:187435", "title": "Differences between the effects of dopamine and apomorphine on rat aortic strips.", "content": "Dopamine and apomorphine have been compared with regard to contraction and relaxation of aortic strips prepared from rats of different ages. Both dopamine and apomorphine contracted aortic strips from older (9-12 weeks) rats to greater maximal tension than preparations from younger (3--5 weeks) animals. Contraction in response to both agonists could be blocked by the alpha-blocker, Dibenamine. In contrast to dopamine contraction by apomorphine was associated with the development of tachyphylaxis. Both apomorphine and dopamine relaxed the aorta after alpha blockade, however, the relaxation produced by these drugs differed in two major aspects. First, dopamine-induced relaxation was greatest in aortic strips from young rats compared to older rats whereas relaxation with apomorphine was not age dependent. Second, dopamine-induced relaxation was abolished by propranolol but not haloperidol whereas apomorphine relaxation was only blocked by haloperidol. These data establish that the aortic relaxation caused by dopamine is most likely a beta-adrenergically mediated response whereas that produced by apomorphine is not. Moreover, only dopamine was able to increase the concentration of rat aortic cyclic AMP. Should these data be applicable to other vascular beds or species, it is possible that the vascular effects of dopamine will be influenced by age and drugs which impinge on cyclic nucleotide disposition.", "contents": "Differences between the effects of dopamine and apomorphine on rat aortic strips. Dopamine and apomorphine have been compared with regard to contraction and relaxation of aortic strips prepared from rats of different ages. Both dopamine and apomorphine contracted aortic strips from older (9-12 weeks) rats to greater maximal tension than preparations from younger (3--5 weeks) animals. Contraction in response to both agonists could be blocked by the alpha-blocker, Dibenamine. In contrast to dopamine contraction by apomorphine was associated with the development of tachyphylaxis. Both apomorphine and dopamine relaxed the aorta after alpha blockade, however, the relaxation produced by these drugs differed in two major aspects. First, dopamine-induced relaxation was greatest in aortic strips from young rats compared to older rats whereas relaxation with apomorphine was not age dependent. Second, dopamine-induced relaxation was abolished by propranolol but not haloperidol whereas apomorphine relaxation was only blocked by haloperidol. These data establish that the aortic relaxation caused by dopamine is most likely a beta-adrenergically mediated response whereas that produced by apomorphine is not. Moreover, only dopamine was able to increase the concentration of rat aortic cyclic AMP. Should these data be applicable to other vascular beds or species, it is possible that the vascular effects of dopamine will be influenced by age and drugs which impinge on cyclic nucleotide disposition."}
{"id": "PMID:187436", "title": "Further study of the adrenoceptors of the saphenous vein of the dog: influence of factors which interfere with the concentrations of agonists at the receptor level.", "content": "In the present study the affinities of some sympathomimetic amines for alpha- and beta-adrenoceptors of the dog saphenous vein tissue were determined after all known factors interfering with the concentration of these agonists at the receptor level had been assessed and excluded. It was observed that in control experiments the relative potencies of sympathomimetic agonists for inducing contractions were: adrenaline (1.6) greater than noradrenaline (1.0) greater than phenylephrine (0.38) greater than isoprenaline (0.009). The elimination of neuronal uptake by cocaine, 4 X 10(-6) M, enhanced predominantly the effects of noradrenaline (by a factor of 7.5), whereas block of catechol-O-methyl transferase (COMT) by U-0521, 10(-4) M, only enhanced those of adrenaline (by a factor of 2.6) and block of beta-adrenoceptors by propranolol, 5 X 10(-7) M, enhanced those of isoprenaline (by a factor of 3) and adrenaline (by a factor of 1.8). Block of COMT enhanced the effects of adrenaline approximately as much as did the blockade of neuronal uptake; this seems to indicate that the affinity of adrenaline for extraneuronal and neuronal uptake processes is approximately the same. Regarding the relaxation-inducing capacity of sympathomimetic agents it was observed that isoprenaline, adrenaline and noradrenaline are full agonists, whereas phenylephrine was not able to produce relaxation amounting to more than 5% of the maximum. Denervation did not modify the relaxant effects of isoprenaline. After elimination of all known factors interfering with the concentration of the sympathomimetic agonists in the biophase, the ratios between the ED50's of each amine for alpha- and beta-adrenoceptors were: adrenaline = 34, noradrenaline = 109 and isoprenaline = 0.0041.", "contents": "Further study of the adrenoceptors of the saphenous vein of the dog: influence of factors which interfere with the concentrations of agonists at the receptor level. In the present study the affinities of some sympathomimetic amines for alpha- and beta-adrenoceptors of the dog saphenous vein tissue were determined after all known factors interfering with the concentration of these agonists at the receptor level had been assessed and excluded. It was observed that in control experiments the relative potencies of sympathomimetic agonists for inducing contractions were: adrenaline (1.6) greater than noradrenaline (1.0) greater than phenylephrine (0.38) greater than isoprenaline (0.009). The elimination of neuronal uptake by cocaine, 4 X 10(-6) M, enhanced predominantly the effects of noradrenaline (by a factor of 7.5), whereas block of catechol-O-methyl transferase (COMT) by U-0521, 10(-4) M, only enhanced those of adrenaline (by a factor of 2.6) and block of beta-adrenoceptors by propranolol, 5 X 10(-7) M, enhanced those of isoprenaline (by a factor of 3) and adrenaline (by a factor of 1.8). Block of COMT enhanced the effects of adrenaline approximately as much as did the blockade of neuronal uptake; this seems to indicate that the affinity of adrenaline for extraneuronal and neuronal uptake processes is approximately the same. Regarding the relaxation-inducing capacity of sympathomimetic agents it was observed that isoprenaline, adrenaline and noradrenaline are full agonists, whereas phenylephrine was not able to produce relaxation amounting to more than 5% of the maximum. Denervation did not modify the relaxant effects of isoprenaline. After elimination of all known factors interfering with the concentration of the sympathomimetic agonists in the biophase, the ratios between the ED50's of each amine for alpha- and beta-adrenoceptors were: adrenaline = 34, noradrenaline = 109 and isoprenaline = 0.0041."}
{"id": "PMID:187442", "title": "Potentiation of excitatory synaptic transmission in the normal and in the reinnervated dentate gyrus of the rat.", "content": "Following destruction of the ipsilateral temporo-ammonic tract, which originates in the entorhinal cortex, and terminates on the granule cells of the dentate gyrus, fibers from the surviving contralateral entorhinal area proliferate forming extensive new connections with the denervated dentate granule cells. Utlizing extracellular recording techniques, we have compared the characteristics of synaptic transmission in the lesion induced afferents with the characteristics of the normal ipsilateral afferents by analyzing the responses of dentate granule cells to paired pulse activation of temporo-dentate circuitry. In the dentate gyrus of the normal rat, and extracellularly recorded EPSP evoked by stimulation of the ipsilateral entorhinal cortex is enhanced by as much as 100% by a \"conditioning\" pulse to the same afferent system. This is called paired pulse potentiation. In the reinnervated dentate gyrus, the extracellular EPSP evoked by a test stimulus delivered to the contralateral entorhinal cortex is also potentiated by a conditioning pulse. Thepaired pulse potentiation in the reinnervated dentate gyrus has a time course which is comparable to that of the normal ipsilateral afferent system, but the magnitude of the potentiation is somewhat less, averaging approximately 140% of control...", "contents": "Potentiation of excitatory synaptic transmission in the normal and in the reinnervated dentate gyrus of the rat. Following destruction of the ipsilateral temporo-ammonic tract, which originates in the entorhinal cortex, and terminates on the granule cells of the dentate gyrus, fibers from the surviving contralateral entorhinal area proliferate forming extensive new connections with the denervated dentate granule cells. Utlizing extracellular recording techniques, we have compared the characteristics of synaptic transmission in the lesion induced afferents with the characteristics of the normal ipsilateral afferents by analyzing the responses of dentate granule cells to paired pulse activation of temporo-dentate circuitry. In the dentate gyrus of the normal rat, and extracellularly recorded EPSP evoked by stimulation of the ipsilateral entorhinal cortex is enhanced by as much as 100% by a \"conditioning\" pulse to the same afferent system. This is called paired pulse potentiation. In the reinnervated dentate gyrus, the extracellular EPSP evoked by a test stimulus delivered to the contralateral entorhinal cortex is also potentiated by a conditioning pulse. Thepaired pulse potentiation in the reinnervated dentate gyrus has a time course which is comparable to that of the normal ipsilateral afferent system, but the magnitude of the potentiation is somewhat less, averaging approximately 140% of control..."}
{"id": "PMID:187459", "title": "Ultrastructure of cultured fibroblasts in mucolipidosis type IV.", "content": "Five patients have been classified as suffering from mucolipidosis type IV on the basis of the findings in various tissues and in cultured fibroblasts. The light and electron microscopic features of cultured fibroblasts in this disease are described in detail. The differentiation of this condition from other lysosomal storage diseases and other types of mucolipidoses is discussed. The importance of identifying this disease for purposes of intrauterine diagnosis and eventual understanding of the underlying enzyme defect is stressed.", "contents": "Ultrastructure of cultured fibroblasts in mucolipidosis type IV. Five patients have been classified as suffering from mucolipidosis type IV on the basis of the findings in various tissues and in cultured fibroblasts. The light and electron microscopic features of cultured fibroblasts in this disease are described in detail. The differentiation of this condition from other lysosomal storage diseases and other types of mucolipidoses is discussed. The importance of identifying this disease for purposes of intrauterine diagnosis and eventual understanding of the underlying enzyme defect is stressed."}
{"id": "PMID:187504", "title": "Cyclic AMP binding to intracellular receptor proteins in rat myometrium. Effect of epinephrine and prostaglandin E1.", "content": "In estrogen-pretreated rat myometrium, the relaxing effect exerted by theophylline or epinephrine has been correlated with their ability to raise cyclic AMP levels (Vesin and Harbon, 1974). The present study demonstrates that such a correlation can be quantitatively extended to the degree of saturation of intracellular cyclic AMP receptors. The rise in cyclic AMP induced by theophylline and/or epinephrine in intact myometrial strips was accompanied by a decrease in the ability of the corresponding extracts to bind exogenous 3H-labeled cyclic AMP. Total intracellular cyclic AMP binding sites were not modified and averaged a value of 0.22 muM. Accurate estimation of intracellular receptor-cyclic AMP complex has been correlated with the corresponding level of cyclic AMP in the tissue, the apparent intracellular Kd for cyclic AMP has been evaluated at 450 nm. Stimulation of myometrial strips with prostaglandin E1 (PGE1) which has been shown previously to induce contractions, although elevating cyclic AMP levels, was accompanied by a parallel increase in the saturation of the endogenous receptor, in an identical manner to that found with epinephrine or theophylline. The postulated hypothesis for a compartmentalization of cyclic AMP, or an interference of PGE1 with the intracellular cyclic AMP binding equilibrium has not been verified. The cyclic AMP system cannot be considered as the exclusive mechanism regulating uterine relaxation.", "contents": "Cyclic AMP binding to intracellular receptor proteins in rat myometrium. Effect of epinephrine and prostaglandin E1. In estrogen-pretreated rat myometrium, the relaxing effect exerted by theophylline or epinephrine has been correlated with their ability to raise cyclic AMP levels (Vesin and Harbon, 1974). The present study demonstrates that such a correlation can be quantitatively extended to the degree of saturation of intracellular cyclic AMP receptors. The rise in cyclic AMP induced by theophylline and/or epinephrine in intact myometrial strips was accompanied by a decrease in the ability of the corresponding extracts to bind exogenous 3H-labeled cyclic AMP. Total intracellular cyclic AMP binding sites were not modified and averaged a value of 0.22 muM. Accurate estimation of intracellular receptor-cyclic AMP complex has been correlated with the corresponding level of cyclic AMP in the tissue, the apparent intracellular Kd for cyclic AMP has been evaluated at 450 nm. Stimulation of myometrial strips with prostaglandin E1 (PGE1) which has been shown previously to induce contractions, although elevating cyclic AMP levels, was accompanied by a parallel increase in the saturation of the endogenous receptor, in an identical manner to that found with epinephrine or theophylline. The postulated hypothesis for a compartmentalization of cyclic AMP, or an interference of PGE1 with the intracellular cyclic AMP binding equilibrium has not been verified. The cyclic AMP system cannot be considered as the exclusive mechanism regulating uterine relaxation."}
{"id": "PMID:187505", "title": "Ontogenesis, distribution and relative sensitivity of hCG receptors to hCG and LH in goat ovaries.", "content": "The binding of [125I]hCG to immature and mature follicles and corpora lutea of goat ovaries has been studied. The hormone is bound maximally by corpora lutea although mature follicles also exhibit some binding. Immature follicles are practically devoid of receptors for this hormone. In the corpus luteum, the receptors for the hormone are present in thecal and luteal cells. Autoradiographic studies show the location of the bound radioactivity grains primarily along the plasma membranes of these cells, although some radioactivity grains were also seen in the cytoplasm of luteal but not thecal cells. On a mole to mole basis, hCG was found to displace [125I]hCG from binding to receptors on corpus luteum better than hLH and oLH.", "contents": "Ontogenesis, distribution and relative sensitivity of hCG receptors to hCG and LH in goat ovaries. The binding of [125I]hCG to immature and mature follicles and corpora lutea of goat ovaries has been studied. The hormone is bound maximally by corpora lutea although mature follicles also exhibit some binding. Immature follicles are practically devoid of receptors for this hormone. In the corpus luteum, the receptors for the hormone are present in thecal and luteal cells. Autoradiographic studies show the location of the bound radioactivity grains primarily along the plasma membranes of these cells, although some radioactivity grains were also seen in the cytoplasm of luteal but not thecal cells. On a mole to mole basis, hCG was found to displace [125I]hCG from binding to receptors on corpus luteum better than hLH and oLH."}
{"id": "PMID:187507", "title": "The use of a multicomponent standard for clostridial vaccines.", "content": "A multicomponent clostridial vaccine in being developed with the objective of acting as a standard preparation for the control of vaccines containing one to eight components. It is intended initially for use in monitoring those components which can be assessed by antitoxin response assays in rabbits. The components involved, therefore, are the principle toxoids of Clostridium (perfringens) welchii types B, C and D, Cl. oedematiens type B, Cl. septicum and Cl. tetani. The proposed standard also contains the toxoid of Cl. oedematiens type D and an anaculture of Cl. chauvoei. It is hoped later to develop the use of the two latter components as standards in other test systems. The aim of establishing the standard was to provide a means of controlling inter-laboratory variation, especially that due to animals.", "contents": "The use of a multicomponent standard for clostridial vaccines. A multicomponent clostridial vaccine in being developed with the objective of acting as a standard preparation for the control of vaccines containing one to eight components. It is intended initially for use in monitoring those components which can be assessed by antitoxin response assays in rabbits. The components involved, therefore, are the principle toxoids of Clostridium (perfringens) welchii types B, C and D, Cl. oedematiens type B, Cl. septicum and Cl. tetani. The proposed standard also contains the toxoid of Cl. oedematiens type D and an anaculture of Cl. chauvoei. It is hoped later to develop the use of the two latter components as standards in other test systems. The aim of establishing the standard was to provide a means of controlling inter-laboratory variation, especially that due to animals."}
{"id": "PMID:187506", "title": "Effects of trypsin and phospholipases A2 and C on enzyme organization in testis microsomes.", "content": "Pregnenolone and progesterone concentrated in the microsomal fraction of cryptorchid mouse testis compared with mitochondria and cytosol. While the concentrating mechanisms had high capacity and low association constants the effect did not seem to be due to nonspecific solubility in the lipid components since 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione and testosterone did not show differential concentration. Also digestion with phospholipases A2 and C to the point where most of the phospholipids were specifically split, only lowered the differential binding of pregnenolone and progesterone by less than half. Trypsin had a greater effect, short digestion at 0 degrees C lowering the specific binding to 35-40% and decreasing the steroid dehydrogenases to a similar extent. The members of the mixed function oxidase system in the testis microsomes were particularly sensitive to trypsin, cytochrome P-450 and, as a consequence, 17alpha-hydroxylase and 17, 20-lyase activity being eliminated under tha same conditions while liver microsomal cytochrome P-450 was hardly affected. Bonds split by trypsin seem to play a more important role in the hydroxylase activity of testis microsomes than in the hepatic system.", "contents": "Effects of trypsin and phospholipases A2 and C on enzyme organization in testis microsomes. Pregnenolone and progesterone concentrated in the microsomal fraction of cryptorchid mouse testis compared with mitochondria and cytosol. While the concentrating mechanisms had high capacity and low association constants the effect did not seem to be due to nonspecific solubility in the lipid components since 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione and testosterone did not show differential concentration. Also digestion with phospholipases A2 and C to the point where most of the phospholipids were specifically split, only lowered the differential binding of pregnenolone and progesterone by less than half. Trypsin had a greater effect, short digestion at 0 degrees C lowering the specific binding to 35-40% and decreasing the steroid dehydrogenases to a similar extent. The members of the mixed function oxidase system in the testis microsomes were particularly sensitive to trypsin, cytochrome P-450 and, as a consequence, 17alpha-hydroxylase and 17, 20-lyase activity being eliminated under tha same conditions while liver microsomal cytochrome P-450 was hardly affected. Bonds split by trypsin seem to play a more important role in the hydroxylase activity of testis microsomes than in the hepatic system."}
{"id": "PMID:187508", "title": "An international survey of clostridial sera and vaccines.", "content": "The papers present the results of a survey of the usage, assay and specification of veterinary clostridial sera and vaccines in 23 countries. Thirteen of the countries use up to 8 different antisera. All the countries use vaccines, which are prepared from 13 species and types of clostridia. Vaccines containing up to 8 such components are commonly employed. Criteria for the design and interpretation of assays are discussed and evidence for efficacy summarized.", "contents": "An international survey of clostridial sera and vaccines. The papers present the results of a survey of the usage, assay and specification of veterinary clostridial sera and vaccines in 23 countries. Thirteen of the countries use up to 8 different antisera. All the countries use vaccines, which are prepared from 13 species and types of clostridia. Vaccines containing up to 8 such components are commonly employed. Criteria for the design and interpretation of assays are discussed and evidence for efficacy summarized."}
{"id": "PMID:187509", "title": "Production and standardization of polyvalent Clostridium perfringens vaccine in Iran.", "content": "In this presentation an account of the large-scale production and the standardization of polyvalent Clostridium perfringens vaccine in Iran is described. Over 20 million doses of this vaccine are produced and utilized in Iran every year. Certain modifications have been made to the culture media used in our laboratory for the production of this vaccine in order to bring down its cost. The prepared vaccine is highly immunogenic as determined by the laboratory examination on the quality of the vaccine according to British Veterinary Codex and the field reports.", "contents": "Production and standardization of polyvalent Clostridium perfringens vaccine in Iran. In this presentation an account of the large-scale production and the standardization of polyvalent Clostridium perfringens vaccine in Iran is described. Over 20 million doses of this vaccine are produced and utilized in Iran every year. Certain modifications have been made to the culture media used in our laboratory for the production of this vaccine in order to bring down its cost. The prepared vaccine is highly immunogenic as determined by the laboratory examination on the quality of the vaccine according to British Veterinary Codex and the field reports."}
{"id": "PMID:187510", "title": "The standardization of Cl. perfringens antigens and antisera.", "content": "The preparation of laboratory standard antitoxins against Cl. perfringens beta and epsilon toxins is described. These antitoxins are suitable for the quantitative determination of the corresponding antigens by means of the flocculation test. The flocculation test was, however, shown to be more suitable for determining the antigenic value of fresh toxoid rather than toxoid stored without neutralization of excess formalin. A maximal immunity response to alum-precipitated epsilon toxoid was obtained in sheep with two injections containing 90 Lf per dose. The interval between these injections may vary from 2 to 6 weeks. The serum-antibody titres after the primary and secondary injections or after a booster dose given before 12 months after the primary injection did not remain above the protective level in most of the sheep injected for longer than about 5 months. When a sound basic immunity is established the degree of protection following on a booster dose given 12 months later is complete for at least 12 months. An alum-precipitated vaccine containing 25 Lf epsilon toxoid per dose is adequate. The decline in the serum-antibody titre during the first year of vaccination could be eliminated by the use of the antigen in water-in-oil emulsion. Lambs from immune dams were protected for at least up to 13 weeks of age. A satisfactory level of circulating antitoxin against Cl. perfringens beta toxin could be produced in ewes by vaccinating them with APT containing 6.25 Lf beta toxoid per dose. The primary and secondary injections could be separated by 2, 3, 4 or 5 weeks without changing the end result. A booster dose given 2 months before parturition was satisfactory.", "contents": "The standardization of Cl. perfringens antigens and antisera. The preparation of laboratory standard antitoxins against Cl. perfringens beta and epsilon toxins is described. These antitoxins are suitable for the quantitative determination of the corresponding antigens by means of the flocculation test. The flocculation test was, however, shown to be more suitable for determining the antigenic value of fresh toxoid rather than toxoid stored without neutralization of excess formalin. A maximal immunity response to alum-precipitated epsilon toxoid was obtained in sheep with two injections containing 90 Lf per dose. The interval between these injections may vary from 2 to 6 weeks. The serum-antibody titres after the primary and secondary injections or after a booster dose given before 12 months after the primary injection did not remain above the protective level in most of the sheep injected for longer than about 5 months. When a sound basic immunity is established the degree of protection following on a booster dose given 12 months later is complete for at least 12 months. An alum-precipitated vaccine containing 25 Lf epsilon toxoid per dose is adequate. The decline in the serum-antibody titre during the first year of vaccination could be eliminated by the use of the antigen in water-in-oil emulsion. Lambs from immune dams were protected for at least up to 13 weeks of age. A satisfactory level of circulating antitoxin against Cl. perfringens beta toxin could be produced in ewes by vaccinating them with APT containing 6.25 Lf beta toxoid per dose. The primary and secondary injections could be separated by 2, 3, 4 or 5 weeks without changing the end result. A booster dose given 2 months before parturition was satisfactory."}
{"id": "PMID:187511", "title": "[Standardization of the control technics of Clostridium perfringens vaccine. Use of a reference vaccine].", "content": "Control of Cl perfringens toxins. It is possible to employ a standardized technique for the control of the toxins of Cl. perfringens. Titres of LD50 per ml for the mouse and L+/50 per ml may be expressed with a confidence limit of 1.5. The assay of toxins by L+/50 (relating to their antigenic value) permits the establishment of standards by which it is possible to obtain a satisfactory vaccine with a high degree of certainty. 10 L+/50 per dose for Cl. perfringens A 20 L+/50 per dose for Cl. perfringens B 180 L+/50 per dose for Cl. perfringens C 50 L+/50 per dose for Cl. perfringens D Control of vaccine values. Technique adopted : Determination of antibodies in the rabbit following vaccination. The confidence limit of the antitoxin titre is similarly equal to 1.5 when P = 0.05. It would not appear to be necessary to establish minimum levels of antibodies to confer protection; it seems nevertheless that the results are influenced by considerable variations attributable to the animals used for the most part and that a reference vaccine is required. Freeze-dried vaccine. There is a natural antigenic activity in the rabbit which retains a considerable part of its antigenic properties after maintenance for one week at +37 degrees C. In our view this would be suitable for a reference vaccine.", "contents": "[Standardization of the control technics of Clostridium perfringens vaccine. Use of a reference vaccine]. Control of Cl perfringens toxins. It is possible to employ a standardized technique for the control of the toxins of Cl. perfringens. Titres of LD50 per ml for the mouse and L+/50 per ml may be expressed with a confidence limit of 1.5. The assay of toxins by L+/50 (relating to their antigenic value) permits the establishment of standards by which it is possible to obtain a satisfactory vaccine with a high degree of certainty. 10 L+/50 per dose for Cl. perfringens A 20 L+/50 per dose for Cl. perfringens B 180 L+/50 per dose for Cl. perfringens C 50 L+/50 per dose for Cl. perfringens D Control of vaccine values. Technique adopted : Determination of antibodies in the rabbit following vaccination. The confidence limit of the antitoxin titre is similarly equal to 1.5 when P = 0.05. It would not appear to be necessary to establish minimum levels of antibodies to confer protection; it seems nevertheless that the results are influenced by considerable variations attributable to the animals used for the most part and that a reference vaccine is required. Freeze-dried vaccine. There is a natural antigenic activity in the rabbit which retains a considerable part of its antigenic properties after maintenance for one week at +37 degrees C. In our view this would be suitable for a reference vaccine."}
{"id": "PMID:187512", "title": "[Comparison between the official indirect method and the direct method of control of vaccines against sheep enterotoxemia].", "content": "The official methods of control of vaccines against sheep enterotoxemia are indirect in two ways : on the one hand they are carried out on animals for which the vaccine is not intended, and on the other hand they test only an immunological serum reaction. Another method consisting of direct testing by intravenous injection of toxin has been carried out on mice previously vaccinated with different doses. It has been shown that it is possible to obtain a certain level of protection giving a good dose-effect relation. However, immunity provided by this direct method is weak although the vaccine utilized is considered very efficacious with regard to the official norms of the direct test. These results, which are both encouraging and disappointing, will be the subject of a more intensive study of the different parameters in question.", "contents": "[Comparison between the official indirect method and the direct method of control of vaccines against sheep enterotoxemia]. The official methods of control of vaccines against sheep enterotoxemia are indirect in two ways : on the one hand they are carried out on animals for which the vaccine is not intended, and on the other hand they test only an immunological serum reaction. Another method consisting of direct testing by intravenous injection of toxin has been carried out on mice previously vaccinated with different doses. It has been shown that it is possible to obtain a certain level of protection giving a good dose-effect relation. However, immunity provided by this direct method is weak although the vaccine utilized is considered very efficacious with regard to the official norms of the direct test. These results, which are both encouraging and disappointing, will be the subject of a more intensive study of the different parameters in question."}
{"id": "PMID:187513", "title": "Experimental studies on serum treatment and vaccination against Cl. perfringens type C infection in piglets.", "content": "Subcutaneous administration of serum to piglets just after birth resulted in serum titres of 9-18 I.U. beta-antitoxin per ml in the first three days of life. At the ages of 7, 14, and 28 days the titres had dropped to about 5-9, 2 and 1 I.U. per ml, respectively. Oral administration of the same dose of serum resulted in serum titres of about half of those found after s.c. administration. In infected herds a significant protective effect after both s.c. and oral administration of serum was found to be dependent on the time of treatment but independent of the route of administration. After vaccination a correlation was noted between the levels of beta-antitoxin in colostral whey and specific mortality in the litters. An initial beta-antitoxin concentration of about 10 I.U. per ml whey seems to be sufficient to secure effective prevention. By vaccination once during gestation the beta-antitoxin levels in colostral whey were all less than 10 I.U. per ml. Two vaccinations during gestation resulted in whey titres greater than 10 I.U. per ml in 12 of 20 dams. By revaccinating once only during the following gestation effective beta-antitoxin levels in colostral whey were secured regardless of whether the vaccination had been performed once or twice during the previous gestation : the mean was 87.4 I.U. beta-antitoxin per ml; three of 20 dams had titres less than 10 I.U. per ml whey. From mortality studies including 63 liters in three infected herds specific mortalities of 17.3% and 4.6% were found after one and two vaccinations respectively, as compared with 36.6% in the control group. After revaccination during the ensuing gestation the figures were 1.4%, 0.0% and 32.2% named in the same order. 2 ml serum given as soon as possible after birth or 5 ml vaccine injected twice during gestation followed by one revaccination during subsequent gestations effectively protect piglets against infection with Cl. perfringens type C.", "contents": "Experimental studies on serum treatment and vaccination against Cl. perfringens type C infection in piglets. Subcutaneous administration of serum to piglets just after birth resulted in serum titres of 9-18 I.U. beta-antitoxin per ml in the first three days of life. At the ages of 7, 14, and 28 days the titres had dropped to about 5-9, 2 and 1 I.U. per ml, respectively. Oral administration of the same dose of serum resulted in serum titres of about half of those found after s.c. administration. In infected herds a significant protective effect after both s.c. and oral administration of serum was found to be dependent on the time of treatment but independent of the route of administration. After vaccination a correlation was noted between the levels of beta-antitoxin in colostral whey and specific mortality in the litters. An initial beta-antitoxin concentration of about 10 I.U. per ml whey seems to be sufficient to secure effective prevention. By vaccination once during gestation the beta-antitoxin levels in colostral whey were all less than 10 I.U. per ml. Two vaccinations during gestation resulted in whey titres greater than 10 I.U. per ml in 12 of 20 dams. By revaccinating once only during the following gestation effective beta-antitoxin levels in colostral whey were secured regardless of whether the vaccination had been performed once or twice during the previous gestation : the mean was 87.4 I.U. beta-antitoxin per ml; three of 20 dams had titres less than 10 I.U. per ml whey. From mortality studies including 63 liters in three infected herds specific mortalities of 17.3% and 4.6% were found after one and two vaccinations respectively, as compared with 36.6% in the control group. After revaccination during the ensuing gestation the figures were 1.4%, 0.0% and 32.2% named in the same order. 2 ml serum given as soon as possible after birth or 5 ml vaccine injected twice during gestation followed by one revaccination during subsequent gestations effectively protect piglets against infection with Cl. perfringens type C."}
{"id": "PMID:187514", "title": "Solid-phase radioimmunoassays for quantitative antibody determination of bacterial exotoxins. Measurement of Clostridium perfringens type D epsilon antitoxin.", "content": "Two reversed solid-phase radioimmunoassays have been developed for quantitative determination of antibodies against Clostridium perfringens type D epsilon toxin. 125I labelled prototoxin was used in the bromoacetyl cellulose-bound antibody method and in the antibody coated tube method. The procedures are based on the competition for 125I labelled prototoxin between the insoluble antibodies and the antibodies present in the unknown sample. The radioactivity bound to solid-phase is in inverse ratio to quantity of measured antibodies. The antibody values which can be detected are in the range of 0.004 IU/ml of investigated serum. The methods allow the rapid and inexpensive screening of large groups of vaccinated sheep, and are very suitable for measuring small amounts of Cl. perfringens D epsilon antibodies with a small experimental error.", "contents": "Solid-phase radioimmunoassays for quantitative antibody determination of bacterial exotoxins. Measurement of Clostridium perfringens type D epsilon antitoxin. Two reversed solid-phase radioimmunoassays have been developed for quantitative determination of antibodies against Clostridium perfringens type D epsilon toxin. 125I labelled prototoxin was used in the bromoacetyl cellulose-bound antibody method and in the antibody coated tube method. The procedures are based on the competition for 125I labelled prototoxin between the insoluble antibodies and the antibodies present in the unknown sample. The radioactivity bound to solid-phase is in inverse ratio to quantity of measured antibodies. The antibody values which can be detected are in the range of 0.004 IU/ml of investigated serum. The methods allow the rapid and inexpensive screening of large groups of vaccinated sheep, and are very suitable for measuring small amounts of Cl. perfringens D epsilon antibodies with a small experimental error."}
{"id": "PMID:187515", "title": "An international serotyping system for Clostridium perfringens (welchii) type A in the near future.", "content": "The importance of Clostridium perfringens (welchii) type A as an agent of clinical infection in man is well known and, more recently, its role as a cause of human food poisoning has become well recognized. There has been a growing awareness of the need for a system of finer subdivision within the type A group for better understanding of the epidemiology of Cl. perfringens in infections and food poisoning. A set of antisera used for typing and developed in the Food Hygiene Laboratory over a period of some years has proved to be of considerable value in this respect; it is now being integrated with similar sets of antisera prepared independently in the USA and Japan to form a comprehensive and internationally workable serotyping scheme. Negotiations regarding commercial production of the main type antisera are now in progress. It is hoped that serotyping facilities will be available in the near future to workers and institutions concerned with Cl. perfringens type A.", "contents": "An international serotyping system for Clostridium perfringens (welchii) type A in the near future. The importance of Clostridium perfringens (welchii) type A as an agent of clinical infection in man is well known and, more recently, its role as a cause of human food poisoning has become well recognized. There has been a growing awareness of the need for a system of finer subdivision within the type A group for better understanding of the epidemiology of Cl. perfringens in infections and food poisoning. A set of antisera used for typing and developed in the Food Hygiene Laboratory over a period of some years has proved to be of considerable value in this respect; it is now being integrated with similar sets of antisera prepared independently in the USA and Japan to form a comprehensive and internationally workable serotyping scheme. Negotiations regarding commercial production of the main type antisera are now in progress. It is hoped that serotyping facilities will be available in the near future to workers and institutions concerned with Cl. perfringens type A."}
{"id": "PMID:187516", "title": "Postheparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus. Relationship to plasma triglyceride metabolism.", "content": "The activity of two triglyceride lipases was determined by an immunochemical method in the postheparin plasma of 60 diabetic patients and of 47 age- and sex-matched nondiabetic control subjects. The results were related to the type of diabetes, to plasma triglyceride and insulin concentrations, to removal of exogenous fat from the blood, and to turnover of VLDL-triglycerides . The mean postheparin plasma lipoprotein lipase (LPL) activity was decreased by 44 per cent (p less than 0.001) in patients with untreated ketotic diabetes and by 20 per cent (p less than 0.01) in patients with untreated mild to moderate nonketotic early-onset diabetes. Insulin treatment of ketotic diabetes resulted in a rapid increase in the activity of LPL and decrease in serum triglycerdie level, whereas sulfonylurea treatment of non-insulin-requiring diabetics did not significantly influence the enzyme activity. In insulin-treated chronic diabetics the average postheparin plasma LPL activity was not different from that of nondiabetic controls, but some of these patients had high LPL values. In normolipidemic maturity-onset-type diabetics the LPL activity was within normal range, but in those having hypertriglyceridemia the average LPL value was decreased by an average of 26 per cent (p less than 0.01). The LPL activity showed a significant negative correlation with the logarithm of serum triglyceride concentration (r = -0.62) and a positive correlation with fractional removal of Intralipid (r = +0.64) and fractional turnover of V triglyceride (r = +0.40). The activity of LPL was correlated to basal plasma insulin concen tration in the insulin-deficient diabetes r = +0.34) but not in patients with maturity-onset-type diabetes. The hepatic lipase (HL) activity of postheparin plasma was similar in diabetes and controls, with the exception of hypertriglyceridemic maturity-onset diabetics, who had higher mean HL activity than the corresponding control group (p greater than 0.01). The activity of HL was not related to triglyceride removal but showed a significant correlation to VLDL-triglyceride production rate. On the basis of these results it seems that a deficiency of LPL accounts for a great deal of the elevation of serum triglyceride in insulin-deficient human diabetes but has a smaller role in the pathogenesis of the hypertriglyceridemia that is associated with maturity-onset diabetes. The latter abnormality is caused mainly by an increased secretion of triglycerides into the blood even though a decreased LPL may contribute to development of hyperlipemia in cases with gross elevation of serum triglycerides.", "contents": "Postheparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus. Relationship to plasma triglyceride metabolism. The activity of two triglyceride lipases was determined by an immunochemical method in the postheparin plasma of 60 diabetic patients and of 47 age- and sex-matched nondiabetic control subjects. The results were related to the type of diabetes, to plasma triglyceride and insulin concentrations, to removal of exogenous fat from the blood, and to turnover of VLDL-triglycerides . The mean postheparin plasma lipoprotein lipase (LPL) activity was decreased by 44 per cent (p less than 0.001) in patients with untreated ketotic diabetes and by 20 per cent (p less than 0.01) in patients with untreated mild to moderate nonketotic early-onset diabetes. Insulin treatment of ketotic diabetes resulted in a rapid increase in the activity of LPL and decrease in serum triglycerdie level, whereas sulfonylurea treatment of non-insulin-requiring diabetics did not significantly influence the enzyme activity. In insulin-treated chronic diabetics the average postheparin plasma LPL activity was not different from that of nondiabetic controls, but some of these patients had high LPL values. In normolipidemic maturity-onset-type diabetics the LPL activity was within normal range, but in those having hypertriglyceridemia the average LPL value was decreased by an average of 26 per cent (p less than 0.01). The LPL activity showed a significant negative correlation with the logarithm of serum triglyceride concentration (r = -0.62) and a positive correlation with fractional removal of Intralipid (r = +0.64) and fractional turnover of V triglyceride (r = +0.40). The activity of LPL was correlated to basal plasma insulin concen tration in the insulin-deficient diabetes r = +0.34) but not in patients with maturity-onset-type diabetes. The hepatic lipase (HL) activity of postheparin plasma was similar in diabetes and controls, with the exception of hypertriglyceridemic maturity-onset diabetics, who had higher mean HL activity than the corresponding control group (p greater than 0.01). The activity of HL was not related to triglyceride removal but showed a significant correlation to VLDL-triglyceride production rate. On the basis of these results it seems that a deficiency of LPL accounts for a great deal of the elevation of serum triglyceride in insulin-deficient human diabetes but has a smaller role in the pathogenesis of the hypertriglyceridemia that is associated with maturity-onset diabetes. The latter abnormality is caused mainly by an increased secretion of triglycerides into the blood even though a decreased LPL may contribute to development of hyperlipemia in cases with gross elevation of serum triglycerides."}
{"id": "PMID:187517", "title": "Role of insulin resistance in adipose tissue and liver in the pathogenesis of endogenous hypertriglyceridaemia in man.", "content": "Studies were performed to evaluate the relative importance of enhanced adipose tissue lipolysis and increased insulin levels in modulating hepatic VLDL production in patients with endogenous hypertriglyceridaemia. Eight control subjects and nine patients with hypertriglyceridaemia were investigated. The latter group comprised four patients with idiopathic hypertriglyceridaemia, three maturity onset diabetics, and two siblings with diabetic lipodystrophy. Each individual's plasma VLDL was selectively labelled with I131 in the apoprotein moiety and then reinjected to assess the turnover of these molecules. This was correlated with the insulin response to an oral glucose load and with the plasma FFA flux measured by a continuous infusion of 14C palmitate. In the patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics, plasma VLDL-appoprotein turnover was increased suggesting enhanced hepatic production of these molecules. Although the insulin levels in these patients were higher than normal, no significant correlation was demonstrable between the plasma insulin and the turnover of VLDL-B-apoprotein. Furthermore, in the two patients with lipo-dystrophy the turnover of plasma VLDL was within the normal range, whereas the plasma insulin responses were the highest among all the patients. These results suggest that hyperinsulinaemia alone is not sufficient to account for the increased VLDL production seen in some of our patients. The plasma FFA flux was raised in the patients with idiopathic hypertriglyceridaemia and in the maturity onset diabetics, and was within the normal range in the two patients with lipodystrophy. Indded, in all the subjects studied a significant correlation was observed between the turnover of plasma VLDL-B-apoprotein and the plasma FFA flux. The results thus indicate that the rate of FFA release to plasma constitutes the predominant factor in determining hepatic output of VLDL and that in the majority of patients with endogenous hypertriglyceridaemia the increased FFA flux resulting from insulin resistance in adipose tissue could effectively increase VLDL production. This process appears to be independent of the prevailing insulin levels, and could occur in the presence of insulin resistance in the liver. The latter, however, could be responsible for the impaired glucose tolerance observed in some patients.", "contents": "Role of insulin resistance in adipose tissue and liver in the pathogenesis of endogenous hypertriglyceridaemia in man. Studies were performed to evaluate the relative importance of enhanced adipose tissue lipolysis and increased insulin levels in modulating hepatic VLDL production in patients with endogenous hypertriglyceridaemia. Eight control subjects and nine patients with hypertriglyceridaemia were investigated. The latter group comprised four patients with idiopathic hypertriglyceridaemia, three maturity onset diabetics, and two siblings with diabetic lipodystrophy. Each individual's plasma VLDL was selectively labelled with I131 in the apoprotein moiety and then reinjected to assess the turnover of these molecules. This was correlated with the insulin response to an oral glucose load and with the plasma FFA flux measured by a continuous infusion of 14C palmitate. In the patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics, plasma VLDL-appoprotein turnover was increased suggesting enhanced hepatic production of these molecules. Although the insulin levels in these patients were higher than normal, no significant correlation was demonstrable between the plasma insulin and the turnover of VLDL-B-apoprotein. Furthermore, in the two patients with lipo-dystrophy the turnover of plasma VLDL was within the normal range, whereas the plasma insulin responses were the highest among all the patients. These results suggest that hyperinsulinaemia alone is not sufficient to account for the increased VLDL production seen in some of our patients. The plasma FFA flux was raised in the patients with idiopathic hypertriglyceridaemia and in the maturity onset diabetics, and was within the normal range in the two patients with lipodystrophy. Indded, in all the subjects studied a significant correlation was observed between the turnover of plasma VLDL-B-apoprotein and the plasma FFA flux. The results thus indicate that the rate of FFA release to plasma constitutes the predominant factor in determining hepatic output of VLDL and that in the majority of patients with endogenous hypertriglyceridaemia the increased FFA flux resulting from insulin resistance in adipose tissue could effectively increase VLDL production. This process appears to be independent of the prevailing insulin levels, and could occur in the presence of insulin resistance in the liver. The latter, however, could be responsible for the impaired glucose tolerance observed in some patients."}
{"id": "PMID:187518", "title": "Decreased cyclic AMP and insulin responses to glucose in pancreatic islets of diabetic Chinese hamsters.", "content": "The dose as well as the time kinetics of insulin and adenosine-3',5'-monophosphate (cyclic AMP) responses to glucose were compared in pancreatic islets isolated from normal and diabetic Chinese hamsters. The insulin content in diabetic islets was about one-half that in normal islets. Insulin release in diabetic islets incubated for 10 min with glucose 60-1000 mg/100 ml was from one-third to one-half that in normal islets. Glucose 1000 mg/100 ml stimulated three-fold increases in insulin release without increasing the accumulation of [3H] cyclic AMP in either normal or diabetic islets prelabelled with [3H] adenine. However, in the presence of 1.0 mM of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), glucose 150 mg/100 ml elicited significant increases of insulin release (+ 134%) and [3H] cyclic AMP accumulation in islets (+ 44%) and incubation medium (+ 48%) of islets of normal but not diabetic hamsters. Also, in perifusion experiments with 0.1 mM IBMX, glucose 500 mg/100 ml produced threefold greater increases in insulin release and two-fold greater increases in efflux of cyclic AMP in normal than diabetic islets. By contrast with the lesser effects of glucose in diabetic islets, 1.0 mM IBMX increased islet and medium cyclic AMP, as well as insulin release, similarly in normal and diabetic islets. It is suggested that the impairment of glucose-induced insulin release in islets of the diabetic Chinese hamster may be due to a defective interaction of glucose with the adenylate cyclase-cyclic AMP system in the pancreatic B cell.", "contents": "Decreased cyclic AMP and insulin responses to glucose in pancreatic islets of diabetic Chinese hamsters. The dose as well as the time kinetics of insulin and adenosine-3',5'-monophosphate (cyclic AMP) responses to glucose were compared in pancreatic islets isolated from normal and diabetic Chinese hamsters. The insulin content in diabetic islets was about one-half that in normal islets. Insulin release in diabetic islets incubated for 10 min with glucose 60-1000 mg/100 ml was from one-third to one-half that in normal islets. Glucose 1000 mg/100 ml stimulated three-fold increases in insulin release without increasing the accumulation of [3H] cyclic AMP in either normal or diabetic islets prelabelled with [3H] adenine. However, in the presence of 1.0 mM of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), glucose 150 mg/100 ml elicited significant increases of insulin release (+ 134%) and [3H] cyclic AMP accumulation in islets (+ 44%) and incubation medium (+ 48%) of islets of normal but not diabetic hamsters. Also, in perifusion experiments with 0.1 mM IBMX, glucose 500 mg/100 ml produced threefold greater increases in insulin release and two-fold greater increases in efflux of cyclic AMP in normal than diabetic islets. By contrast with the lesser effects of glucose in diabetic islets, 1.0 mM IBMX increased islet and medium cyclic AMP, as well as insulin release, similarly in normal and diabetic islets. It is suggested that the impairment of glucose-induced insulin release in islets of the diabetic Chinese hamster may be due to a defective interaction of glucose with the adenylate cyclase-cyclic AMP system in the pancreatic B cell."}
{"id": "PMID:187519", "title": "Abnormalities in the adrenergic control and the rate of lipolysis in isolated human subcutaneous adipose tissue in diabetes mellitus.", "content": "Subcutaneous adipose tissue was obtained from 9 patients with untreated diabetes mellitus and from 13 obese nondiabetics. After incubation with isoprenaline or noradrenaline, glycerol release and tissue cyclic AMP (cAMP) were determined. Basal glycerol release was twice as rapid from the diabetic adipose tissue. With isoprenaline, the cAMP concentration and the glycerol production was significantly higher in the diabetic adipose tissue. Noradrenaline did not increase glycerol production or cAMP concentration in the diabetic adipose tissue. Subcutaneous adipose tissue was also removed from the diabetics after antidiabetic treatment. Basal lipolysis was significantly reduced and noradrenaline significantly increased both glycerol release and cAMP production. With isoprenaline, cAMP production and glycerol release were significantly less after antidiabetic treatment than in the untreated state. The data provide evidence for increased alpha- as well as beta-adrenergic receptor sensitivity in human subcutaneous adipose tissue of untreated diabetic patients.", "contents": "Abnormalities in the adrenergic control and the rate of lipolysis in isolated human subcutaneous adipose tissue in diabetes mellitus. Subcutaneous adipose tissue was obtained from 9 patients with untreated diabetes mellitus and from 13 obese nondiabetics. After incubation with isoprenaline or noradrenaline, glycerol release and tissue cyclic AMP (cAMP) were determined. Basal glycerol release was twice as rapid from the diabetic adipose tissue. With isoprenaline, the cAMP concentration and the glycerol production was significantly higher in the diabetic adipose tissue. Noradrenaline did not increase glycerol production or cAMP concentration in the diabetic adipose tissue. Subcutaneous adipose tissue was also removed from the diabetics after antidiabetic treatment. Basal lipolysis was significantly reduced and noradrenaline significantly increased both glycerol release and cAMP production. With isoprenaline, cAMP production and glycerol release were significantly less after antidiabetic treatment than in the untreated state. The data provide evidence for increased alpha- as well as beta-adrenergic receptor sensitivity in human subcutaneous adipose tissue of untreated diabetic patients."}
{"id": "PMID:187520", "title": "Some properties and electrophoretic patterns of rat liver esterases in relation to hepatocarcinogenesis by 3'-methyl-4-(dimethylamino) azobenzene.", "content": "Five distinctly different types of naphthyl acetate esterase in rat liver were examined for study of liver enzymes during hepatocarcinogenesis. Three types of esterase in normal adult liver were separated by column chromatography. Main esterase in adult hepatocytes, which was demonstrated near the origin in cellulose acetate electrophoresis, was very sensitive to diisopropyl phosphorofluoridate (DFP). The other two esterases showed different electrophoretic mobility, while their Km values did not differ and both were considerably resistant to DFP. An anodic minor component in normal adult liver, which had a characteristic esterase pattern of infant liver, increased in the liver of rats fed 3'-methyl-4-(dimethylamino) azobenzene. This esterase was obtained by electrophoresis on Cellogel block. It was partially inhibited by DFP and p-chloromercuribenzoate, activated by cysteine, and showed a different Km value from the above esterases. Another minor component situated at the most cathodic side, which had characteristic esterase patterns of fetal liver and hepatoma, was very sensitive to DFP and eserine, and showed a characteristic of nonspecific cholinesterase as proved by staining.", "contents": "Some properties and electrophoretic patterns of rat liver esterases in relation to hepatocarcinogenesis by 3'-methyl-4-(dimethylamino) azobenzene. Five distinctly different types of naphthyl acetate esterase in rat liver were examined for study of liver enzymes during hepatocarcinogenesis. Three types of esterase in normal adult liver were separated by column chromatography. Main esterase in adult hepatocytes, which was demonstrated near the origin in cellulose acetate electrophoresis, was very sensitive to diisopropyl phosphorofluoridate (DFP). The other two esterases showed different electrophoretic mobility, while their Km values did not differ and both were considerably resistant to DFP. An anodic minor component in normal adult liver, which had a characteristic esterase pattern of infant liver, increased in the liver of rats fed 3'-methyl-4-(dimethylamino) azobenzene. This esterase was obtained by electrophoresis on Cellogel block. It was partially inhibited by DFP and p-chloromercuribenzoate, activated by cysteine, and showed a different Km value from the above esterases. Another minor component situated at the most cathodic side, which had characteristic esterase patterns of fetal liver and hepatoma, was very sensitive to DFP and eserine, and showed a characteristic of nonspecific cholinesterase as proved by staining."}
{"id": "PMID:187521", "title": "Type-C RNA viruses and leukemogenesis: relation of type-C virus infectivity and leukemogenesis induced by nitrosourea compounds in mice.", "content": "Correlation between infectivity of type-C RNA virus) murine leukemia virus, MLV) and development of leukemia was tested  in female ICR/JCL mice treated with either 1-ethyl-1-nitrosourea (ENU) or 1-butyl-1-nitrosourea (BNU). Continuous administration of either chemicals resulted in the occurrence of thymic lymphoma in every mouse with a short latent period. The time of appearance and distribution pattern of MLV infectivity in various tissues were examined by the XC plaque assay technique at fixed intervals during the leukemogenic treatment. In ENU- or BNU-treated mice, only a few samples of the thymus showed MLV infectivity with rather low titers during incubation period and the presence of MLV was not consistent even in leukemic cases though the thymus was almost invariably the target of leukemogenesis. On the other hand, many samples of the uterus, spleen, and mesenteric node from non-leukemic and leukemic mice harbored a good quantity of MLV. In tissues such as the liver, kidney, bone marrow, and muscle, positive cases occurred only sporadically. Observations on the MLV infectivity in untreated controls were almost comparable with those in leukemogen-treated mice. These results indicate that the infectivity of MLV, detected by the XC plaque assay technique, is not necessarily related to the induction of leukemia in mice by exogenous agents.", "contents": "Type-C RNA viruses and leukemogenesis: relation of type-C virus infectivity and leukemogenesis induced by nitrosourea compounds in mice. Correlation between infectivity of type-C RNA virus) murine leukemia virus, MLV) and development of leukemia was tested  in female ICR/JCL mice treated with either 1-ethyl-1-nitrosourea (ENU) or 1-butyl-1-nitrosourea (BNU). Continuous administration of either chemicals resulted in the occurrence of thymic lymphoma in every mouse with a short latent period. The time of appearance and distribution pattern of MLV infectivity in various tissues were examined by the XC plaque assay technique at fixed intervals during the leukemogenic treatment. In ENU- or BNU-treated mice, only a few samples of the thymus showed MLV infectivity with rather low titers during incubation period and the presence of MLV was not consistent even in leukemic cases though the thymus was almost invariably the target of leukemogenesis. On the other hand, many samples of the uterus, spleen, and mesenteric node from non-leukemic and leukemic mice harbored a good quantity of MLV. In tissues such as the liver, kidney, bone marrow, and muscle, positive cases occurred only sporadically. Observations on the MLV infectivity in untreated controls were almost comparable with those in leukemogen-treated mice. These results indicate that the infectivity of MLV, detected by the XC plaque assay technique, is not necessarily related to the induction of leukemia in mice by exogenous agents."}
{"id": "PMID:187522", "title": "An experimental model for lymphatic metastasis in rats.", "content": "An experimental model was described for inducing spontaneous lymph node metastasis, in which tumor cells of the rat ascites hepatoma AH-109A were transplanted into the subcutaneous tissue of the penis, which is rich of lymph plexus. Growth of tumor at the site of transplantation was measured serially and metastasis was recognized by palpation in the inguinal lymph nodes initially, and then in the axillary and lumbar nodes. When animals were sacrificed 12 days after transplantation, these lymph nodes were weighed and high percentage of metastasis was confirmed by histological examination. As an experimental model of lymph node metastasis, the usefulness of this method was discussed.", "contents": "An experimental model for lymphatic metastasis in rats. An experimental model was described for inducing spontaneous lymph node metastasis, in which tumor cells of the rat ascites hepatoma AH-109A were transplanted into the subcutaneous tissue of the penis, which is rich of lymph plexus. Growth of tumor at the site of transplantation was measured serially and metastasis was recognized by palpation in the inguinal lymph nodes initially, and then in the axillary and lumbar nodes. When animals were sacrificed 12 days after transplantation, these lymph nodes were weighed and high percentage of metastasis was confirmed by histological examination. As an experimental model of lymph node metastasis, the usefulness of this method was discussed."}
{"id": "PMID:187523", "title": "Viral DNA in inflammatory bowel disease. CMV-bearing cells as a target for immune-mediated enterocytolysis.", "content": "Althouth serological studies have revealed a high incidence and mean titer of antibody to cytomegalovirus (CMV) in some patients with inflammatory bowel disease, electron microscopy has not confirmed the presence of mature virus in diseased tissue. Sensitive biochemical techniques for detection of viral nucleic acid were applied therefore to test the proposed disease-virus association. Membrane cRNA-DNA hybridization showed that CMV DNA was not detectable in 3 cases of Crohn's disease, nor was it present in 3 or 4 cases of ulcerative colitis examined. Five tissue specimens taken 5 cm away from a colonic tumor were also negative. An in situ hybridization study of diseased tissue, including specimens from 6 inflammatory bowel disease patients in addition to those above, showed a few grains distributed over cells superficial to the muscularis mucosa, but was not regarded as significantly different from controls. The association of CMV with Crohn's disease (0 positives in 4 patients by either test) is not supported by this study; the association with ulcerative colitis (1 positive in 9 patients by either test) requires further study before a definitive conclusion can be made.", "contents": "Viral DNA in inflammatory bowel disease. CMV-bearing cells as a target for immune-mediated enterocytolysis. Althouth serological studies have revealed a high incidence and mean titer of antibody to cytomegalovirus (CMV) in some patients with inflammatory bowel disease, electron microscopy has not confirmed the presence of mature virus in diseased tissue. Sensitive biochemical techniques for detection of viral nucleic acid were applied therefore to test the proposed disease-virus association. Membrane cRNA-DNA hybridization showed that CMV DNA was not detectable in 3 cases of Crohn's disease, nor was it present in 3 or 4 cases of ulcerative colitis examined. Five tissue specimens taken 5 cm away from a colonic tumor were also negative. An in situ hybridization study of diseased tissue, including specimens from 6 inflammatory bowel disease patients in addition to those above, showed a few grains distributed over cells superficial to the muscularis mucosa, but was not regarded as significantly different from controls. The association of CMV with Crohn's disease (0 positives in 4 patients by either test) is not supported by this study; the association with ulcerative colitis (1 positive in 9 patients by either test) requires further study before a definitive conclusion can be made."}
{"id": "PMID:187524", "title": "Rat gastric mucosal adenylyl cyclase.", "content": "Prostaglandin E1, epinephrine, secretin, and glucagon are known inhibitors of gastric acid secretion, and each agent stimulated mucosal membrane (600 X g pellet) adenylyl cyclase activity from the corpus of the rat stomach. This adenylyl cyclase activity was also stimulated by 5'-guanylyl-imidodiphosphate and sodium fluoride but not by guanosine-5'-triphosphate. By contrast, the gastric acid secretagogues, pentagastrin, histamine, and carbachol, had no effect on basal or prostaglandin E1-stimulated mucosal adenylyl cyclase activity. Most of the sodium fluoride- and hormone-stimulated adenylyl cyclase of the corpus mucosa was contained in the 600 X g membrane fraction. The enzyme exhibited Michaelis-Menten kinetics with respect to the concentration of ATP, with an apparent Km of 0.25 mM. Histamine did not stimulate rat mucosal adenylyl cyclase activity under a variety of conditions, but did stimulate the same enzyme in guinea pig gastric fundic mucosa, an enzyme also activated by prostaglandin E1. These studies do not support the hypothesis that cyclic AMP mediates the actions of gastric acid secretagogues on the parietal cell in the rat.", "contents": "Rat gastric mucosal adenylyl cyclase. Prostaglandin E1, epinephrine, secretin, and glucagon are known inhibitors of gastric acid secretion, and each agent stimulated mucosal membrane (600 X g pellet) adenylyl cyclase activity from the corpus of the rat stomach. This adenylyl cyclase activity was also stimulated by 5'-guanylyl-imidodiphosphate and sodium fluoride but not by guanosine-5'-triphosphate. By contrast, the gastric acid secretagogues, pentagastrin, histamine, and carbachol, had no effect on basal or prostaglandin E1-stimulated mucosal adenylyl cyclase activity. Most of the sodium fluoride- and hormone-stimulated adenylyl cyclase of the corpus mucosa was contained in the 600 X g membrane fraction. The enzyme exhibited Michaelis-Menten kinetics with respect to the concentration of ATP, with an apparent Km of 0.25 mM. Histamine did not stimulate rat mucosal adenylyl cyclase activity under a variety of conditions, but did stimulate the same enzyme in guinea pig gastric fundic mucosa, an enzyme also activated by prostaglandin E1. These studies do not support the hypothesis that cyclic AMP mediates the actions of gastric acid secretagogues on the parietal cell in the rat."}
{"id": "PMID:187525", "title": "Activation of rat gastric mucosal adenylyl cyclase by secretory inhibitors.", "content": "Prostaglandin (PG) E1, E2, A1, and A2 stimulated rat gastric corpus mucosal membrane adenylyl cyclase activity. PGE1 (Kalpha congruent to 8 muM) affected the maximum velocity but not the affinity of the enzyme for ATP and maximum PGE1 activation was not affected by histamine H1 or H2 receptor antagonists. 5'-Guanylyl-diphosphoimide (Gpp(NH)p), but not GTP, stimulated both the basal and PGE1-stimulated adenylyl cyclase activities, although the percentage stimulation by maximal PGE was the same with or without Gpp(NH)p. NaF stimulation was also additive to that of PGE1. Secretin also stimulated gastric mucosal adenylyl cyclase activity (Kalpha congruent to 30 nM). Maximal secretin activation was not additive to that of PGE1, suggesting a coupling to the same adenylyl cyclase catalytic site. These studies suggest that mucosal membranes may contain beta-adrenergic receptors. The adenylyl cyclase activating agents used in this study, PGE1, secretin, and the catecholamines, are all known inhibitors of gastric acid secretion, suggesting a possible involvement of cyclic AMP in the inhibition of acid secretion in the rat stomach.", "contents": "Activation of rat gastric mucosal adenylyl cyclase by secretory inhibitors. Prostaglandin (PG) E1, E2, A1, and A2 stimulated rat gastric corpus mucosal membrane adenylyl cyclase activity. PGE1 (Kalpha congruent to 8 muM) affected the maximum velocity but not the affinity of the enzyme for ATP and maximum PGE1 activation was not affected by histamine H1 or H2 receptor antagonists. 5'-Guanylyl-diphosphoimide (Gpp(NH)p), but not GTP, stimulated both the basal and PGE1-stimulated adenylyl cyclase activities, although the percentage stimulation by maximal PGE was the same with or without Gpp(NH)p. NaF stimulation was also additive to that of PGE1. Secretin also stimulated gastric mucosal adenylyl cyclase activity (Kalpha congruent to 30 nM). Maximal secretin activation was not additive to that of PGE1, suggesting a coupling to the same adenylyl cyclase catalytic site. These studies suggest that mucosal membranes may contain beta-adrenergic receptors. The adenylyl cyclase activating agents used in this study, PGE1, secretin, and the catecholamines, are all known inhibitors of gastric acid secretion, suggesting a possible involvement of cyclic AMP in the inhibition of acid secretion in the rat stomach."}
{"id": "PMID:187526", "title": "Canine Zollinger-Ellison syndrome.", "content": "The unusual finding of peptic esophagitis and duodenal ulceration in a dog was associated with a malignant pancreatic islet cell tumor producing gastrin and ACTH. The finding of a gastrinoma in a non-human species introduces the potential for developing an animal model for the study of the protean genetic biochemical, physiologic and metabolic aspects of the Zollinger-Ellison syndrome.", "contents": "Canine Zollinger-Ellison syndrome. The unusual finding of peptic esophagitis and duodenal ulceration in a dog was associated with a malignant pancreatic islet cell tumor producing gastrin and ACTH. The finding of a gastrinoma in a non-human species introduces the potential for developing an animal model for the study of the protean genetic biochemical, physiologic and metabolic aspects of the Zollinger-Ellison syndrome."}
{"id": "PMID:187527", "title": "Isolation and characterization of X-linked mutants of Drosophila melanogaster which are sensitive to mutagens.", "content": "Thirteen X-linked mutants have been isolated in Drosophila melanogaster which render male and homozygous female larvae sensitive to the mutagen methyl methanesulfonate. Their characterization and preliminary assignment to functional groups is described. Four of these mutants are alleles of mei-41 (Baker and Carpenter 1972). Like previously isolated alleles of this locus, these mutants reduce fertility and increase loss and nondisjunction of the X-chromosome in homozygous females. The remaining mutants have been tentatively assigned to six functional groups (two mutants to the mus(1)101 locus, two to mus(1)102 , two to mus(1)103, and one each to mus(1)104, mus(1)105 , and mus(1)106). Several of the complementation groups can be distinguished on the basis of nondisjunction and cross sensitivity to mutagens. Females homozygous for the mei-41, mus(1)101 and mus(1)102 mutants exhibit elevated levels of nondisjunction. Mutants belonging to complementation groups mei-41, mus(1)101, and mus(1)104 are sensitive to nitrogen mustard (HN2) in addition to their MMS sensitivity. Among these mutants there is currently a direct correlation between sensitivity to HN2, sensitivity to 2-acetylaminofluorene and a deficiency in post-replication repair ( Boyd and Setlow 1976). Only the mei-41 mutants are hypersensitive to UV radiation, although several of the mutants exhibit sensitivity to gamma-rays. Semidominance is observed in female larvae of the mei-41, mus(1)104, and mus(1)103 mutants after exposure to high concentrations of MMS. The properties of the mutants generally conform to a pattern which has been established for related mutants in yeast. Additional properties of these mutants are summarized in Table 9.", "contents": "Isolation and characterization of X-linked mutants of Drosophila melanogaster which are sensitive to mutagens. Thirteen X-linked mutants have been isolated in Drosophila melanogaster which render male and homozygous female larvae sensitive to the mutagen methyl methanesulfonate. Their characterization and preliminary assignment to functional groups is described. Four of these mutants are alleles of mei-41 (Baker and Carpenter 1972). Like previously isolated alleles of this locus, these mutants reduce fertility and increase loss and nondisjunction of the X-chromosome in homozygous females. The remaining mutants have been tentatively assigned to six functional groups (two mutants to the mus(1)101 locus, two to mus(1)102 , two to mus(1)103, and one each to mus(1)104, mus(1)105 , and mus(1)106). Several of the complementation groups can be distinguished on the basis of nondisjunction and cross sensitivity to mutagens. Females homozygous for the mei-41, mus(1)101 and mus(1)102 mutants exhibit elevated levels of nondisjunction. Mutants belonging to complementation groups mei-41, mus(1)101, and mus(1)104 are sensitive to nitrogen mustard (HN2) in addition to their MMS sensitivity. Among these mutants there is currently a direct correlation between sensitivity to HN2, sensitivity to 2-acetylaminofluorene and a deficiency in post-replication repair ( Boyd and Setlow 1976). Only the mei-41 mutants are hypersensitive to UV radiation, although several of the mutants exhibit sensitivity to gamma-rays. Semidominance is observed in female larvae of the mei-41, mus(1)104, and mus(1)103 mutants after exposure to high concentrations of MMS. The properties of the mutants generally conform to a pattern which has been established for related mutants in yeast. Additional properties of these mutants are summarized in Table 9."}
{"id": "PMID:187528", "title": "[Effect of 2,6-diaminopurine resistance mutations on adenine and adenosine assimilation by cells of an adenine-dependent strain of Escherichia coli K-12].", "content": "In purine-requiring strain of Escherichia coli K-12 defective in purine nucleoside phosphorylase (pur, pup) mutants (designated apt) have been obtained that are resistant to 2,6-diaminopurine on guanine-containing medium and incapable to utilize adenine for their growth at 42degreesC, but they are still sensitive to the analogue and can utilize adenine at 28degreesC. It has been shown that the introduction of the corresponding apt mutations in the genome of adenine-requiring strains impaired the ability of these strains to grow on both adenine and adenosine at 42degreesC.", "contents": "[Effect of 2,6-diaminopurine resistance mutations on adenine and adenosine assimilation by cells of an adenine-dependent strain of Escherichia coli K-12]. In purine-requiring strain of Escherichia coli K-12 defective in purine nucleoside phosphorylase (pur, pup) mutants (designated apt) have been obtained that are resistant to 2,6-diaminopurine on guanine-containing medium and incapable to utilize adenine for their growth at 42degreesC, but they are still sensitive to the analogue and can utilize adenine at 28degreesC. It has been shown that the introduction of the corresponding apt mutations in the genome of adenine-requiring strains impaired the ability of these strains to grow on both adenine and adenosine at 42degreesC."}
{"id": "PMID:187532", "title": "[The radiology of Egyptian mummies (author's transl)].", "content": "The technique used for the radiological examination of a well preserved mummy is described. Problems of identification and determination of age, size and sex are discussed. Post mortem changes consist of subluxation of the cervical spine and fractures of the ribs and fibulae. Of medical interest, it was possible to diagnose definitely Scheuermann's disease with a scoliosis and marked reactive spondylotic and spondylo-arthritic changes. The radiological findings provided further information regarding the technique of mummification and the method of burial. Some findings of mythological significance could be demonstrated radiologically, such as the fact that the heart and kidneys had been left in the body, the presence of a scarab, various gold plates and amulets and a fayence-decorated shroud.", "contents": "[The radiology of Egyptian mummies (author's transl)]. The technique used for the radiological examination of a well preserved mummy is described. Problems of identification and determination of age, size and sex are discussed. Post mortem changes consist of subluxation of the cervical spine and fractures of the ribs and fibulae. Of medical interest, it was possible to diagnose definitely Scheuermann's disease with a scoliosis and marked reactive spondylotic and spondylo-arthritic changes. The radiological findings provided further information regarding the technique of mummification and the method of burial. Some findings of mythological significance could be demonstrated radiologically, such as the fact that the heart and kidneys had been left in the body, the presence of a scarab, various gold plates and amulets and a fayence-decorated shroud."}
{"id": "PMID:187533", "title": "[Studies on the regulatory factors of 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) activity].", "content": "HMG CoA reductase, which catalyzes the reaction, HMG CoA + 2 NADAPH2 leads to mevalonate + CoA-SH + 2 NADP, is considered to be the rate-limiting enzyme on cholesterol biosynthetic pathway. Since a degree in activity of this enzyme is almost proportional to the rate of cholesterol synthesis from acetate, elucidation of factors that regulate reductase activity would provide insight into the control mechanisms on the cholesterol biosynthesis. In the present study, attempts were made to establish standard assay conditions of HMG CoA reductase activiy, and to qualify the factors affecting the activity of the enzyme. The results obtained were as follows: (1) As standard assay conditions of HMG CoA reductase activity, 85, muM were chosen for substrate concentration, 25-80 mug for microsomal enzyme protein, and 20 min for incubation time in a final volume of 0.1 ml. (2) HMG CoA reductase activity of rat liver microsomes was exhibited diurnal variation. The level of reductase activity at night was 4 fold higher than that of at daytime. (3) Either ATP or insulin administration stimulated hepatic HMG CoA reductase activity. But, cyclic AMP had no effect on reductase activity. The stimulatory effect of ATP or insulin on reductase activity was inhibited by a preadministration of glucagon. These results suggested that an interplay of hormone might regulate reductase activity and consequently cholesterol biosynthesis. (4) HMG CoA reductase activity was increased by preincubation of microsomes with cytosol. Presence of ATP or Mg++ intensified this effect. When digested by trypsin or degenerated by heat treatment, cytosol lost the stimulating activity. These results suggested as existence of protein factors in cytosol, which might modulate the enzyme interconversion from inactive to active forms.", "contents": "[Studies on the regulatory factors of 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) activity]. HMG CoA reductase, which catalyzes the reaction, HMG CoA + 2 NADAPH2 leads to mevalonate + CoA-SH + 2 NADP, is considered to be the rate-limiting enzyme on cholesterol biosynthetic pathway. Since a degree in activity of this enzyme is almost proportional to the rate of cholesterol synthesis from acetate, elucidation of factors that regulate reductase activity would provide insight into the control mechanisms on the cholesterol biosynthesis. In the present study, attempts were made to establish standard assay conditions of HMG CoA reductase activiy, and to qualify the factors affecting the activity of the enzyme. The results obtained were as follows: (1) As standard assay conditions of HMG CoA reductase activity, 85, muM were chosen for substrate concentration, 25-80 mug for microsomal enzyme protein, and 20 min for incubation time in a final volume of 0.1 ml. (2) HMG CoA reductase activity of rat liver microsomes was exhibited diurnal variation. The level of reductase activity at night was 4 fold higher than that of at daytime. (3) Either ATP or insulin administration stimulated hepatic HMG CoA reductase activity. But, cyclic AMP had no effect on reductase activity. The stimulatory effect of ATP or insulin on reductase activity was inhibited by a preadministration of glucagon. These results suggested that an interplay of hormone might regulate reductase activity and consequently cholesterol biosynthesis. (4) HMG CoA reductase activity was increased by preincubation of microsomes with cytosol. Presence of ATP or Mg++ intensified this effect. When digested by trypsin or degenerated by heat treatment, cytosol lost the stimulating activity. These results suggested as existence of protein factors in cytosol, which might modulate the enzyme interconversion from inactive to active forms."}
{"id": "PMID:187534", "title": "Glucose metabolism in isolated fat cells: enhanced response of larger adipocytes from older rats to epinephrine and adrenocorticotropin.", "content": "The effects of insulin and of two lipolytic hormones (epinephrine and ACTH1) on the rate and pattern of glucose metabolism were compared during incubation of isolated fat cells, obtained from epididymal fat pads of rats of varying age and degrees of adiposity. Glucose metabolism and the intracellular free fatty acid levels were expressed on a per cell basis and in relation to adipocyte size. The data for total glucose metabolism show that, in contrast to the declining insulin effect observed with adipocyte enlargement, the stimulation of glucose uptake and metabolism by these lipolytic hormones was significantly greater in the larger fat cells from the older fatter rats than in the smaller ones from the younger leaner rats. Lipolytic hormones suppressed, whereas insulin enhanced, fatty acid synthesis; moreover the lipolytic hormones stiumlated glucose ce effect of epinephrine on the intracellular free fatty acid levels was greater in the small fat cells than in the large ones; this effect of epinephrine was markedly curtained by the presence of glucose in the incubation medium, making it unlikely that acceleration of glucose metabolism by the lipolytic stimulus was mediated by an elevation of the intracellular free fatty acid level. The present results show a markedly enhanced capacity of the large adipocytes to accelerate glucose metabolism in response to these liplytic hormones. Thus, in contrast to prevailing notions of declining hormonal responsiveness with expanding fat cell size in older and more obese animals, this study documents an instance of increased hormonal response in enlarged adipocytes and points to the need for a more comprehensive reevaluation of the various hormonal effects in adipocytes of different size.", "contents": "Glucose metabolism in isolated fat cells: enhanced response of larger adipocytes from older rats to epinephrine and adrenocorticotropin. The effects of insulin and of two lipolytic hormones (epinephrine and ACTH1) on the rate and pattern of glucose metabolism were compared during incubation of isolated fat cells, obtained from epididymal fat pads of rats of varying age and degrees of adiposity. Glucose metabolism and the intracellular free fatty acid levels were expressed on a per cell basis and in relation to adipocyte size. The data for total glucose metabolism show that, in contrast to the declining insulin effect observed with adipocyte enlargement, the stimulation of glucose uptake and metabolism by these lipolytic hormones was significantly greater in the larger fat cells from the older fatter rats than in the smaller ones from the younger leaner rats. Lipolytic hormones suppressed, whereas insulin enhanced, fatty acid synthesis; moreover the lipolytic hormones stiumlated glucose ce effect of epinephrine on the intracellular free fatty acid levels was greater in the small fat cells than in the large ones; this effect of epinephrine was markedly curtained by the presence of glucose in the incubation medium, making it unlikely that acceleration of glucose metabolism by the lipolytic stimulus was mediated by an elevation of the intracellular free fatty acid level. The present results show a markedly enhanced capacity of the large adipocytes to accelerate glucose metabolism in response to these liplytic hormones. Thus, in contrast to prevailing notions of declining hormonal responsiveness with expanding fat cell size in older and more obese animals, this study documents an instance of increased hormonal response in enlarged adipocytes and points to the need for a more comprehensive reevaluation of the various hormonal effects in adipocytes of different size."}
{"id": "PMID:187535", "title": "Adrenal insufficiency secondary to hypothalamic corticotropin releasing factor (CRF) insufficiency with hyperpigmentation: a case report.", "content": "Partial adrenocortical insufficiency as a result of an insufficiency of the hypothalamic corticotropin releasing factor (CRF) was demonstrated in a 53-year-old female patient. Somatotropic, gonadotropic and thyreotropic functions of the pituitary gland were shown to be normal by a simultaneous pituitary stimulation test. This held true especially for the adrenocorticotrophic function: administration of lysine-vasopressin induced a normal rise in immunoreactive plasma-ACTH. Thus, a pituitary defect as a primary cause of the disease could be excluded and evidence was provided that there was a lack in hypothalamic stimulae absence of elevated ACTH levels hyperpigmentation of the skin existed. Possible explanations are discussed.", "contents": "Adrenal insufficiency secondary to hypothalamic corticotropin releasing factor (CRF) insufficiency with hyperpigmentation: a case report. Partial adrenocortical insufficiency as a result of an insufficiency of the hypothalamic corticotropin releasing factor (CRF) was demonstrated in a 53-year-old female patient. Somatotropic, gonadotropic and thyreotropic functions of the pituitary gland were shown to be normal by a simultaneous pituitary stimulation test. This held true especially for the adrenocorticotrophic function: administration of lysine-vasopressin induced a normal rise in immunoreactive plasma-ACTH. Thus, a pituitary defect as a primary cause of the disease could be excluded and evidence was provided that there was a lack in hypothalamic stimulae absence of elevated ACTH levels hyperpigmentation of the skin existed. Possible explanations are discussed."}
{"id": "PMID:187536", "title": "Cyclic AMP, glucose and cortisol in plasma during surgery.", "content": "Cyclic AMP, glucose and cortisol in plasma were measured before, during and after major surgery (hysterectomy, six patients) and minor surgery (tympanoplasty, 10 patients). During major surgery cyclic AMP as well as glucose and cortisol showed a pronounced increase. During minor surgery cyclic AMP, glucose and cortisol levels were significantly lower than in the group undergoing major surgery. It is concluded that the increase of plasma cyclic AMP during operative procedures is related to the severity of the trauma.", "contents": "Cyclic AMP, glucose and cortisol in plasma during surgery. Cyclic AMP, glucose and cortisol in plasma were measured before, during and after major surgery (hysterectomy, six patients) and minor surgery (tympanoplasty, 10 patients). During major surgery cyclic AMP as well as glucose and cortisol showed a pronounced increase. During minor surgery cyclic AMP, glucose and cortisol levels were significantly lower than in the group undergoing major surgery. It is concluded that the increase of plasma cyclic AMP during operative procedures is related to the severity of the trauma."}
{"id": "PMID:187537", "title": "Parathyroid hormone and calcitonin: no direct effect on vitamin D3-mediated, intestinal calcium absorptive mechanism.", "content": "Embryonic chick duodenum maintained in organ culture responds to vitamin D3 in the culture medium by increased cyclic AMP concentration, de novo synthesis of a specific calcium-binding protein and by increased uptake and transmucosal transport of radiocalcium. The presence of bovine PTH, porcine or salmon calcitonin had no effect on these intestinal responses suggesting that these hormones may have no direct effect on the vitamin D3-mediated, intestinal calcium absorptive mechanism.", "contents": "Parathyroid hormone and calcitonin: no direct effect on vitamin D3-mediated, intestinal calcium absorptive mechanism. Embryonic chick duodenum maintained in organ culture responds to vitamin D3 in the culture medium by increased cyclic AMP concentration, de novo synthesis of a specific calcium-binding protein and by increased uptake and transmucosal transport of radiocalcium. The presence of bovine PTH, porcine or salmon calcitonin had no effect on these intestinal responses suggesting that these hormones may have no direct effect on the vitamin D3-mediated, intestinal calcium absorptive mechanism."}
{"id": "PMID:187540", "title": "Reversal of the unresponsiveness of neonatal rat ovary to LH in cAMP synthesis by estrogen.", "content": "The rat ovary during the 1st postnatal week is unresponsive to luteinizing hormone (LH), but responds to prostaglandin E1 with increase of cyclic adenosine 3',5'-monophosphate synthesis. In the present experiments unresponsiveness of ovaries of 6-day-old rats to LH in synthesis of cAMP was effectively reversed by injection of depot estradiol and diethylstilbestrol on the 2nd and 4th postnatal day. Administration of testosterone, progesterone, deoxycorticosterone, pregnant mare's serum gonadotropin and human chronic gonadotropin had no stimulatory effect. The lack of response to LH also failed to be reversed when estradiol was injected 21 h before killing of the animals or the ovaries were preincubated with estradiol. These results suggest that the development of an ovarian cell system responsive to LH in newborn rat may be accelerated by long-term action of estradiol.", "contents": "Reversal of the unresponsiveness of neonatal rat ovary to LH in cAMP synthesis by estrogen. The rat ovary during the 1st postnatal week is unresponsive to luteinizing hormone (LH), but responds to prostaglandin E1 with increase of cyclic adenosine 3',5'-monophosphate synthesis. In the present experiments unresponsiveness of ovaries of 6-day-old rats to LH in synthesis of cAMP was effectively reversed by injection of depot estradiol and diethylstilbestrol on the 2nd and 4th postnatal day. Administration of testosterone, progesterone, deoxycorticosterone, pregnant mare's serum gonadotropin and human chronic gonadotropin had no stimulatory effect. The lack of response to LH also failed to be reversed when estradiol was injected 21 h before killing of the animals or the ovaries were preincubated with estradiol. These results suggest that the development of an ovarian cell system responsive to LH in newborn rat may be accelerated by long-term action of estradiol."}
{"id": "PMID:187542", "title": "Hereditary hemolytic anemia with erythrocyte pyrimidine 5'-nucleotidase deficiency in Spain. Clinical, biological and familial studies.", "content": "We report a hereditary hemolytic anemia associated with a severe erythrocyte pyrimidine 5'-nucleotidase deficiency in a Spanish family of five members in which the parents are first cousins. Both parents exhibited decreased nucleotidase activity without clinical or hematologic abnormalities. Two children (a male and a female) showed severe pyrimidine 5'-nucleotidase deficiency with hemolytic anemia. The remaining child (a male) showed no signs of the disease. The findings strongly suggest an autosomal recessive mode of inheritance in this enzymopathy. This seems to be the first report of pyrimidine 5'-nucleotidase deficiency in Spain.", "contents": "Hereditary hemolytic anemia with erythrocyte pyrimidine 5'-nucleotidase deficiency in Spain. Clinical, biological and familial studies. We report a hereditary hemolytic anemia associated with a severe erythrocyte pyrimidine 5'-nucleotidase deficiency in a Spanish family of five members in which the parents are first cousins. Both parents exhibited decreased nucleotidase activity without clinical or hematologic abnormalities. Two children (a male and a female) showed severe pyrimidine 5'-nucleotidase deficiency with hemolytic anemia. The remaining child (a male) showed no signs of the disease. The findings strongly suggest an autosomal recessive mode of inheritance in this enzymopathy. This seems to be the first report of pyrimidine 5'-nucleotidase deficiency in Spain."}
{"id": "PMID:187545", "title": "Experimental herpes simplex virus carditis in mice.", "content": "Herpes simplex virus types 1 and 2 induced acute and chronic cardiac damage in suckling and weaning mice after intranasal inoculation. Signs of virus replication were detected by light, immunofluorescent, and electron microscopy techniques. Virtually all of the cardiac tissues appeared to be susceptible to herpes simplex virus. The myocardium, however, was most regularly affected. The viral lesions were discrete during the acute phase of infection. The cardiac damage, however, was more extensive in some of the chronically infected mice. Morphologically, these lesions either resembled the acute ones or were associated with inflammatory granulomatous and sclerotic changes.", "contents": "Experimental herpes simplex virus carditis in mice. Herpes simplex virus types 1 and 2 induced acute and chronic cardiac damage in suckling and weaning mice after intranasal inoculation. Signs of virus replication were detected by light, immunofluorescent, and electron microscopy techniques. Virtually all of the cardiac tissues appeared to be susceptible to herpes simplex virus. The myocardium, however, was most regularly affected. The viral lesions were discrete during the acute phase of infection. The cardiac damage, however, was more extensive in some of the chronically infected mice. Morphologically, these lesions either resembled the acute ones or were associated with inflammatory granulomatous and sclerotic changes."}
{"id": "PMID:187546", "title": "Effects of beta-adrenergic blockade on plasma cyclic AMP and blood sugar responses to glucagon and isoproterenol in man.", "content": "In healthy humans glucagon infusion resulted in a significant increase in blood sugar and in plasma cyclic AMP. No discernible hemodynamic effects were found. Isoproterenol infusion on a mole per mole basis in the same subjects induced a significant, although less pronounced rise in plasma cyclic AMP, heart rate, and a fall in diastolic blood pressure but had no effect on blood sugar. Propranolol administration abolished the hemodynamic effects of isoproterenol and significantly decreased the response of plasma cyclic AMP; the same blocking dosage had little effect on plasma cyclic AMP changes induced  by glucagon wheras the response in blood sugar was significantly reduced. These data in vivo are compatible with the in vitro demonstration of separate receptors for glucagon and isoproterenol.", "contents": "Effects of beta-adrenergic blockade on plasma cyclic AMP and blood sugar responses to glucagon and isoproterenol in man. In healthy humans glucagon infusion resulted in a significant increase in blood sugar and in plasma cyclic AMP. No discernible hemodynamic effects were found. Isoproterenol infusion on a mole per mole basis in the same subjects induced a significant, although less pronounced rise in plasma cyclic AMP, heart rate, and a fall in diastolic blood pressure but had no effect on blood sugar. Propranolol administration abolished the hemodynamic effects of isoproterenol and significantly decreased the response of plasma cyclic AMP; the same blocking dosage had little effect on plasma cyclic AMP changes induced  by glucagon wheras the response in blood sugar was significantly reduced. These data in vivo are compatible with the in vitro demonstration of separate receptors for glucagon and isoproterenol."}
{"id": "PMID:187547", "title": "In vitro evaluation of some latent radioprotective compounds.", "content": "In tissue culture, protection against X-irradiation by a number of cysteamine derivatives was studied and the results were compared with data obtained in mice. Compounds with a covered SH group, like WR 638, cysteamine phosphate, WR 2721, and AE 48527, showed practically no protection when dissolved in tissue-culture medium, but developed a protective activity when dissolved in rat blood. Thiol measurements demonstrated that in rat blood the compounds were partly hydrolysed to thiols. C511 was also hydrolysed in culture medium and was slightly less effective than cysteamine in culture medium. Cysteamine phosphate was hydrolsed more easily than cysteamine sulphate and the protective activity in rat blood was better. WR 2721 was also partly hydrolysed in rat blood. The in vitro protection of this compound was disappointing when compared with results in vivo. Its SH form (WR 1065) also showed less protection than expected from in vivo experiments. Thus, the little protection by WR 2721 in vitro in rat blood is not only due to its incomplete conversion into its thiol. Longer incubation times and the use of rat blood as a solvent brought the protective activity of WR 1065 almost up to the level of cysteamine. This may indicate that WR 1065 penetrates the cells poorly. WR 1065 was the only compound we studied whose protective activity in vitro was improved appreciably by dissolving it in rat plasma.", "contents": "In vitro evaluation of some latent radioprotective compounds. In tissue culture, protection against X-irradiation by a number of cysteamine derivatives was studied and the results were compared with data obtained in mice. Compounds with a covered SH group, like WR 638, cysteamine phosphate, WR 2721, and AE 48527, showed practically no protection when dissolved in tissue-culture medium, but developed a protective activity when dissolved in rat blood. Thiol measurements demonstrated that in rat blood the compounds were partly hydrolysed to thiols. C511 was also hydrolysed in culture medium and was slightly less effective than cysteamine in culture medium. Cysteamine phosphate was hydrolsed more easily than cysteamine sulphate and the protective activity in rat blood was better. WR 2721 was also partly hydrolysed in rat blood. The in vitro protection of this compound was disappointing when compared with results in vivo. Its SH form (WR 1065) also showed less protection than expected from in vivo experiments. Thus, the little protection by WR 2721 in vitro in rat blood is not only due to its incomplete conversion into its thiol. Longer incubation times and the use of rat blood as a solvent brought the protective activity of WR 1065 almost up to the level of cysteamine. This may indicate that WR 1065 penetrates the cells poorly. WR 1065 was the only compound we studied whose protective activity in vitro was improved appreciably by dissolving it in rat plasma."}
{"id": "PMID:187548", "title": "Studies of short-lived radicals in the gamma-irradiated aqueous solution of uridine-5'-monophosphate by the spin-trapping method and the liquid chromatography.", "content": "An aerated aqueous solution of uridine-5'-monophosphate was gamma-irradiated with 2-methyl-2-nitrosopropane as a spin-trapping reagent. Liquid chromatography was applied to separate the stable nitroxide radicals in the irradiated solution. The radicals were detected by U.V. and e.s.r. spectrometry. The e.s.r. detection showed four peaks in the chromatogram. The orcinol method for detection of the residual sugar moieties was applied before and after reduction of the base to determine the existence of the 5,6-double bond for the molecules in each fraction. From the combined results of the e.s.r. and orcinol methods, the short-lived radicals which were trapped by 2-methyl-2-nitrosopropane were identified as radicals of N-1 and C-6 positions of the base moiety and t-butyl radical which was the radiolytic product of the trapping reagent.", "contents": "Studies of short-lived radicals in the gamma-irradiated aqueous solution of uridine-5'-monophosphate by the spin-trapping method and the liquid chromatography. An aerated aqueous solution of uridine-5'-monophosphate was gamma-irradiated with 2-methyl-2-nitrosopropane as a spin-trapping reagent. Liquid chromatography was applied to separate the stable nitroxide radicals in the irradiated solution. The radicals were detected by U.V. and e.s.r. spectrometry. The e.s.r. detection showed four peaks in the chromatogram. The orcinol method for detection of the residual sugar moieties was applied before and after reduction of the base to determine the existence of the 5,6-double bond for the molecules in each fraction. From the combined results of the e.s.r. and orcinol methods, the short-lived radicals which were trapped by 2-methyl-2-nitrosopropane were identified as radicals of N-1 and C-6 positions of the base moiety and t-butyl radical which was the radiolytic product of the trapping reagent."}
{"id": "PMID:187554", "title": "Polyadenylation of ribonucleic acids in mouse L cells infected by encephalomyocarditis virus.", "content": "Polyadenylation of cytoplasmic RNAs was investigated in L cells infected with encephalomyocarditis virus. During the early stage of infection, the mean size of newly made poly(A) chains attached to cell mRNAs decreased gradually, in parallel with the shut-off of RNA synthesis. Later on, poly(A) segments, an average of 50 nucleotides long, were associated with viral RNA isolated either from polysomes or whole cytoplasm. These segments seemed to be processed differently in the course of time, and RNA molecules containing short poly(A) tracts (less than 20 bases) were incorporated into the virions.", "contents": "Polyadenylation of ribonucleic acids in mouse L cells infected by encephalomyocarditis virus. Polyadenylation of cytoplasmic RNAs was investigated in L cells infected with encephalomyocarditis virus. During the early stage of infection, the mean size of newly made poly(A) chains attached to cell mRNAs decreased gradually, in parallel with the shut-off of RNA synthesis. Later on, poly(A) segments, an average of 50 nucleotides long, were associated with viral RNA isolated either from polysomes or whole cytoplasm. These segments seemed to be processed differently in the course of time, and RNA molecules containing short poly(A) tracts (less than 20 bases) were incorporated into the virions."}
{"id": "PMID:187555", "title": "Uncontrolled nuclear division in murine cells abortively transformed by simian virus 40.", "content": "Cytochalasin B (CB) prevents cytoplasmic cleavage without directly affecting nuclear division. Secondary cultures of mouse embryo fibroblasts or 3T3 cells show controlled nuclear division when treated with CB: only binucleated cells are formed. Many CB-treated transformed cells show uncontrolled nuclear division and become highly multinucleated. When CB-treated normal cells are concurrently infected with high inputs of SV40, many of these cells become highly multinucleated. It is suggested that these highly multinucleated cells represent abortively transformed cells since the actual number of transforming units (focus-forming units) of simian virus 40 (SV40) is too low to account for the appearance of these cells. Also, if the CB treatment is begun 6 days after SV40 inoculation, the large increase in highly multinucleated cells is not observed. Most cells stably transformed by SV40 or adenovirus show uncontrolled nuclear division when treated with CB. However, 3T3 cells transformed by SV40 or adenovirus and analyzed shortly after transformation are an exception and show controlled nuclear division. This property of 3T3 cells is apparently overcome by high inputs of SV40 since abortively transformed cells become highly multinucleated.", "contents": "Uncontrolled nuclear division in murine cells abortively transformed by simian virus 40. Cytochalasin B (CB) prevents cytoplasmic cleavage without directly affecting nuclear division. Secondary cultures of mouse embryo fibroblasts or 3T3 cells show controlled nuclear division when treated with CB: only binucleated cells are formed. Many CB-treated transformed cells show uncontrolled nuclear division and become highly multinucleated. When CB-treated normal cells are concurrently infected with high inputs of SV40, many of these cells become highly multinucleated. It is suggested that these highly multinucleated cells represent abortively transformed cells since the actual number of transforming units (focus-forming units) of simian virus 40 (SV40) is too low to account for the appearance of these cells. Also, if the CB treatment is begun 6 days after SV40 inoculation, the large increase in highly multinucleated cells is not observed. Most cells stably transformed by SV40 or adenovirus show uncontrolled nuclear division when treated with CB. However, 3T3 cells transformed by SV40 or adenovirus and analyzed shortly after transformation are an exception and show controlled nuclear division. This property of 3T3 cells is apparently overcome by high inputs of SV40 since abortively transformed cells become highly multinucleated."}
{"id": "PMID:187551", "title": "Lacalization of the SV40 T antigen in hamster cells transformed by PARA(3ct)-adenovirus 7.", "content": "The localization of the SV40 T antigen in hamster cells transformed by the PARA(3ct)-adenovirus 7 variant and, for comparison, by SV40 was examined. The H50 cell strain (transformed by SV40) and the P7-/BL/SV/OD strain (transformed by PARA(3ct)-adenovirus 7) showed a preferential localization of the SV40 T antigen in the nucleus both by immunofluorescence and by complement fixation. On the other hand, two different PARA(3ct)-adenovirus 7-transformed cell lines (P7-/Ar/d/15A and P7/Ar/m/14A) showed an almost equivalent concentration of the SV40 T antigen in the nucleus and in the cytoplasm both by immunofluorescence and complement fixation. The H50, P7-/BL/SV/3D, P7/Ar/m/14A cells were oncogenic for hamsters; the P7/Ar/d/15A line was not.", "contents": "Lacalization of the SV40 T antigen in hamster cells transformed by PARA(3ct)-adenovirus 7. The localization of the SV40 T antigen in hamster cells transformed by the PARA(3ct)-adenovirus 7 variant and, for comparison, by SV40 was examined. The H50 cell strain (transformed by SV40) and the P7-/BL/SV/OD strain (transformed by PARA(3ct)-adenovirus 7) showed a preferential localization of the SV40 T antigen in the nucleus both by immunofluorescence and by complement fixation. On the other hand, two different PARA(3ct)-adenovirus 7-transformed cell lines (P7-/Ar/d/15A and P7/Ar/m/14A) showed an almost equivalent concentration of the SV40 T antigen in the nucleus and in the cytoplasm both by immunofluorescence and complement fixation. The H50, P7-/BL/SV/3D, P7/Ar/m/14A cells were oncogenic for hamsters; the P7/Ar/d/15A line was not."}
{"id": "PMID:187556", "title": "Replicating DNA of herpes simplex virus type 1.", "content": "Newly synthesized herpes simplex virus type 1 DNA yielded a heterogeneous sedimentation profile in neutral sucrose gradients, with the main peak occurring at approximately 40S. Components sedimenting slower than virion DNA and a rapidly sedimenting intracellular HSV DNA were also observed. Both the low-molecular weight and the rapidly sedimenting components seemed to be precursors of virion DNA: they almost completely disappeared after a 60-min chase of a 3-min pulse of 3H-thymidine, and were converted into DNA which cosedimented with virion 32P-labeled DNA. However, sedimentation analysis in alkaline sucrose gradients showed that a 60-min period was insufficient for completing the maturation of HSV DNA. Cleavage of parental DNA molecules was observed in neutral sucrose gradients after infection with 3H-thymidine-labeled virions. No evidence for the formation of covalently closed circles during the replication process was obtained. The presence of single-stranded regions in the replicative form of HSV DNA was revealed. Some of the short-pulse (30 sec) labeled HSV DNA (26.1%) was eluted from hydroxylapatite columns with the properties of single-stranded DNA, and 22% of its trichloroacetic acid precipitability was susceptible to single-strand specific S1 nuclease treatment. Pulse-chase experiments indicated that the life-time of this single-stranded component in nascent DNA was probably not longer than 3 min. A small proportion of single-stranded regions, however, survived for longer periods. Almost all of the newly synthesized short-pulse-labeled HSV DNA exhibited an affinity for nitrocellulose filters. This affinity, which was S1 nuclease-sensitive, gradually decreased with prolongation of the time of the chase. After chasing the pulse for 1 h, the attachment of newly synthesized DNA was comparable with virion DNA.", "contents": "Replicating DNA of herpes simplex virus type 1. Newly synthesized herpes simplex virus type 1 DNA yielded a heterogeneous sedimentation profile in neutral sucrose gradients, with the main peak occurring at approximately 40S. Components sedimenting slower than virion DNA and a rapidly sedimenting intracellular HSV DNA were also observed. Both the low-molecular weight and the rapidly sedimenting components seemed to be precursors of virion DNA: they almost completely disappeared after a 60-min chase of a 3-min pulse of 3H-thymidine, and were converted into DNA which cosedimented with virion 32P-labeled DNA. However, sedimentation analysis in alkaline sucrose gradients showed that a 60-min period was insufficient for completing the maturation of HSV DNA. Cleavage of parental DNA molecules was observed in neutral sucrose gradients after infection with 3H-thymidine-labeled virions. No evidence for the formation of covalently closed circles during the replication process was obtained. The presence of single-stranded regions in the replicative form of HSV DNA was revealed. Some of the short-pulse (30 sec) labeled HSV DNA (26.1%) was eluted from hydroxylapatite columns with the properties of single-stranded DNA, and 22% of its trichloroacetic acid precipitability was susceptible to single-strand specific S1 nuclease treatment. Pulse-chase experiments indicated that the life-time of this single-stranded component in nascent DNA was probably not longer than 3 min. A small proportion of single-stranded regions, however, survived for longer periods. Almost all of the newly synthesized short-pulse-labeled HSV DNA exhibited an affinity for nitrocellulose filters. This affinity, which was S1 nuclease-sensitive, gradually decreased with prolongation of the time of the chase. After chasing the pulse for 1 h, the attachment of newly synthesized DNA was comparable with virion DNA."}
{"id": "PMID:187552", "title": "Comparison of DNA polymerase activities induced by herpes simplex virus types 1 and 2.", "content": "HSV-2-induced a salt-stimulated DNA polymerase activity in HEp-2 cells at similar levels to that induced by HSV-1 virus at multiplicites of infection from 2 to 20 PFU/cell. De novo synthesis of protein and mRNA was required for DNA polymerase induction by both types. DNA polymerase activity of three strains of each type was compared by response to various salt concentrations and by heat inactivation. Strain-dependent, but not type-dependent differences were found by both tests. Considerable cross-neutralization of polymerase activity was obtained with specific antisera. The DNA polymerase activity induced by HSV-1 and HSV-2 cannot be readily differentiated by these criteria.", "contents": "Comparison of DNA polymerase activities induced by herpes simplex virus types 1 and 2. HSV-2-induced a salt-stimulated DNA polymerase activity in HEp-2 cells at similar levels to that induced by HSV-1 virus at multiplicites of infection from 2 to 20 PFU/cell. De novo synthesis of protein and mRNA was required for DNA polymerase induction by both types. DNA polymerase activity of three strains of each type was compared by response to various salt concentrations and by heat inactivation. Strain-dependent, but not type-dependent differences were found by both tests. Considerable cross-neutralization of polymerase activity was obtained with specific antisera. The DNA polymerase activity induced by HSV-1 and HSV-2 cannot be readily differentiated by these criteria."}
{"id": "PMID:187553", "title": "Size of the poly(A) sequences in encephalomyocarditis virus RNA.", "content": "Poly(A) sequences were demonstrated in the RNA of encephalomyocarditis (EMC) virus by affinity chromatography on poly(U)-Sepharose, treatment with RNases, and determination of the ability of the RNA to prime for reverse transcription. The size of the poly(A) sequences was estimated as 10-20 nucleotides in length by determination of the fraction resistant to pancreatic RNases plus T1 RNases, followed by analysis of electrophoretic mobility on polyacrylamide gels and of the AMP-to-adenosine ratio after alkaline hydrolysis. The poly(A) sequences are located at the 3' end of the RNA as shown by mild digestion by snake venom phosphodiesterase.", "contents": "Size of the poly(A) sequences in encephalomyocarditis virus RNA. Poly(A) sequences were demonstrated in the RNA of encephalomyocarditis (EMC) virus by affinity chromatography on poly(U)-Sepharose, treatment with RNases, and determination of the ability of the RNA to prime for reverse transcription. The size of the poly(A) sequences was estimated as 10-20 nucleotides in length by determination of the fraction resistant to pancreatic RNases plus T1 RNases, followed by analysis of electrophoretic mobility on polyacrylamide gels and of the AMP-to-adenosine ratio after alkaline hydrolysis. The poly(A) sequences are located at the 3' end of the RNA as shown by mild digestion by snake venom phosphodiesterase."}
{"id": "PMID:187564", "title": "Effect of pasteurization and heat treatment on bovine leukemia virus.", "content": "Four sheep inoculated with mixtures of bovine leukemia virus (BLV) and milk that was treated by a simulated high-temperature short-time pasteurization procedure did not become infected with BLV or develop tumor. Four sheep inoculated with unpasteurized BLV-mil mixtures became infected with BLV and 3 died with tumor at 15, 21, and 27 months, respectively, after inoculation. Fluid from a BLV-infected cell culture was heated to 56, 60, 65, and 73 C for 1/2 minute and 1 minute (in separate trials) and transferred to noninfected cells. Culture fluid heated to 60 C and higher did not infect the cells.", "contents": "Effect of pasteurization and heat treatment on bovine leukemia virus. Four sheep inoculated with mixtures of bovine leukemia virus (BLV) and milk that was treated by a simulated high-temperature short-time pasteurization procedure did not become infected with BLV or develop tumor. Four sheep inoculated with unpasteurized BLV-mil mixtures became infected with BLV and 3 died with tumor at 15, 21, and 27 months, respectively, after inoculation. Fluid from a BLV-infected cell culture was heated to 56, 60, 65, and 73 C for 1/2 minute and 1 minute (in separate trials) and transferred to noninfected cells. Culture fluid heated to 60 C and higher did not infect the cells."}
{"id": "PMID:187565", "title": "Natural infection of pigs with bovine viral diarrhea virus and its differential diagnosis from hog cholera.", "content": "Natural infection of pigs with bovine viral diarrhea virus (BVDV) through contact with infected cattle has caused problems in diagnosing hog cholera (HC). Low cross-reacting serum antibody titers against HC caused by BVDV infection were found in clinically normal pigs as well as those suspected of having HC. Bovine viral diarrhea virus was isolated from specimen tissues and initially identified as HC virus (HCV), using the fluorescent antibody cell culture technique. Additional cell cultures, as well as pig and calf trials, were necessary to identify it as BVDV. The isolate caused clinical signs of illness in the calves, whereas the pigs remained healthy. Bovine viral diarrhea virus may be detected in tissue sections or isolated in cell cultures and confirmed as HCV, using the HC fluorescent antibody conjugate. Laboratories performing the neutralization test for HC should use discretion when interpreting HC titers unless BVD titers are determined on the same serums.", "contents": "Natural infection of pigs with bovine viral diarrhea virus and its differential diagnosis from hog cholera. Natural infection of pigs with bovine viral diarrhea virus (BVDV) through contact with infected cattle has caused problems in diagnosing hog cholera (HC). Low cross-reacting serum antibody titers against HC caused by BVDV infection were found in clinically normal pigs as well as those suspected of having HC. Bovine viral diarrhea virus was isolated from specimen tissues and initially identified as HC virus (HCV), using the fluorescent antibody cell culture technique. Additional cell cultures, as well as pig and calf trials, were necessary to identify it as BVDV. The isolate caused clinical signs of illness in the calves, whereas the pigs remained healthy. Bovine viral diarrhea virus may be detected in tissue sections or isolated in cell cultures and confirmed as HCV, using the HC fluorescent antibody conjugate. Laboratories performing the neutralization test for HC should use discretion when interpreting HC titers unless BVD titers are determined on the same serums."}
{"id": "PMID:187567", "title": "Pathologic features of polybrominated biphenyl toxicosis in the rat and guinea pig.", "content": "Young male rats were fed a diet containing 0, 1, 10, 100, or 500 ppm of a commercial mixture of polybrominated biphenyls (PBB) that had been accidentally incorporated into a mineral mixture and fed to Michigan livestock and poultry. After 30 days, 9 of the 12 rats in each group were killed and tissues were examined. Liver weight to body weight ratios were significantly increased at all feeding levels; at 500 ppm, liver weight had more than doubled. Kidney weight was not affected. Microscopic lesions were mostly confined to the liver and consisted of extensive swelling and vacuolation of hepatocytes in rats fed diets containing 100 and 500 ppm of PBB. Slight swelling and vacuolation were seen in rats fed the diet containing 10 ppm, and lesions were not found at 0 or 1 ppm. There was a significant increase in hepatic mitochondrial size at 1 ppm, and smooth endoplasmic reticulum was markedly increased at 100 and 500 ppm. Myelin bodies were present at 100 and 500 ppm, and vacuoles were numerous. Rats killed at 60 days had similar lesions. The activity of hepatic microsomal enzymes increased at all levels of feeding of PBB. Rat pups nursing dams fed a diet containing 10 ppm of PBB had microscopic and ultrastructural hepatic lesions. When guinea pigs were fed PBB at the same amounts as were rats, the results were strikingly different. Guinea pigs fed a diet containing 500 ppm of PBB died within 15 days; at 100 ppm, only 2 of 6 survived for 30 days. Effects on liver weight were inconsistent, but 2 of 6 fed a diet containing 10 ppm had enlarged livers.", "contents": "Pathologic features of polybrominated biphenyl toxicosis in the rat and guinea pig. Young male rats were fed a diet containing 0, 1, 10, 100, or 500 ppm of a commercial mixture of polybrominated biphenyls (PBB) that had been accidentally incorporated into a mineral mixture and fed to Michigan livestock and poultry. After 30 days, 9 of the 12 rats in each group were killed and tissues were examined. Liver weight to body weight ratios were significantly increased at all feeding levels; at 500 ppm, liver weight had more than doubled. Kidney weight was not affected. Microscopic lesions were mostly confined to the liver and consisted of extensive swelling and vacuolation of hepatocytes in rats fed diets containing 100 and 500 ppm of PBB. Slight swelling and vacuolation were seen in rats fed the diet containing 10 ppm, and lesions were not found at 0 or 1 ppm. There was a significant increase in hepatic mitochondrial size at 1 ppm, and smooth endoplasmic reticulum was markedly increased at 100 and 500 ppm. Myelin bodies were present at 100 and 500 ppm, and vacuoles were numerous. Rats killed at 60 days had similar lesions. The activity of hepatic microsomal enzymes increased at all levels of feeding of PBB. Rat pups nursing dams fed a diet containing 10 ppm of PBB had microscopic and ultrastructural hepatic lesions. When guinea pigs were fed PBB at the same amounts as were rats, the results were strikingly different. Guinea pigs fed a diet containing 500 ppm of PBB died within 15 days; at 100 ppm, only 2 of 6 survived for 30 days. Effects on liver weight were inconsistent, but 2 of 6 fed a diet containing 10 ppm had enlarged livers."}
{"id": "PMID:187568", "title": "Carbohydrate metabolism of heat-acclimated hamsters. V. Control of gluconeogenesis.", "content": "The rate of gluconeogenesis was similar in liver of both fed heat-acclimated and control hamsters. Twenty-four hours of fasting calsed 6 times elevation in hepatic gluconeogenesis of the control animals whereas only 4 times enhancement of this pathway was found in heat-acclimated animals. Thus, significant difference existed between the two experimental groups in fasting. Triiodothyronine stimulated the rate of gluconeogenesis only in fed heat-acclimated hamsters whereas dibutyryl cyclic AMP caused elevation of this pathway in liver slices of fed control hamsters only. The results suggest that a decrease in hepatic gluconeogenesis in heat acclimation occurs only in fasted animals and it is controlled by thyroid hormones.", "contents": "Carbohydrate metabolism of heat-acclimated hamsters. V. Control of gluconeogenesis. The rate of gluconeogenesis was similar in liver of both fed heat-acclimated and control hamsters. Twenty-four hours of fasting calsed 6 times elevation in hepatic gluconeogenesis of the control animals whereas only 4 times enhancement of this pathway was found in heat-acclimated animals. Thus, significant difference existed between the two experimental groups in fasting. Triiodothyronine stimulated the rate of gluconeogenesis only in fed heat-acclimated hamsters whereas dibutyryl cyclic AMP caused elevation of this pathway in liver slices of fed control hamsters only. The results suggest that a decrease in hepatic gluconeogenesis in heat acclimation occurs only in fasted animals and it is controlled by thyroid hormones."}
{"id": "PMID:187569", "title": "Mitochondrial biogenesis during fungal spore germination: respiratory cytochromes of dormant and germinating spores of Botryodiplodia.", "content": "The mitochondrial respiratory cytochrome contents of dormant and germinating conidia of Botryodiplodia theobromae were examined. Oxidized versus reduced difference spectra at 77 degrees K of whole mitochondria from physiologically mature germinated spores showed a typical a-band pattern for cytochromes c, b, and a, with absorption maxima at 549, 554 + 559, and 604 nm, respectively, whereas the difference spectrum of the counterpart mitochondrial fraction from dormant spores showed no cytochrome a bands. However, a fraction prepared from dormant spore mitochondria by detergent extraction and (NH4)2SO4 fractionation contained readily detectable quantities of cytochromes c and b (as shown by the a and Soret absorption bands), but it did not contain the a or Soret bands of cytochrome a observed in a counterpart preparation from germinated spores. The pyridine hemochromogen preparation from the dormant spore mitochondria contained no material that is spectroscopically characteristic of a-type heme and protoheme. These results suggest that cytochrome a is not present as a functional molecule in dormant spores. The first spectroscopically detectable cytochromes were observed in whole mitochondria at 210 min of spore germination, and the amount of each of the cytochromes increased with cell growth. A precursor of the heme porphyrin, delta-[4-14C]aminolevulinic acid, was first incorporated (at accelerating rates) into acid-insoluble spore material at 180 min of germination, which appears to be the approximate time of organization of new mitochondria in these spores.", "contents": "Mitochondrial biogenesis during fungal spore germination: respiratory cytochromes of dormant and germinating spores of Botryodiplodia. The mitochondrial respiratory cytochrome contents of dormant and germinating conidia of Botryodiplodia theobromae were examined. Oxidized versus reduced difference spectra at 77 degrees K of whole mitochondria from physiologically mature germinated spores showed a typical a-band pattern for cytochromes c, b, and a, with absorption maxima at 549, 554 + 559, and 604 nm, respectively, whereas the difference spectrum of the counterpart mitochondrial fraction from dormant spores showed no cytochrome a bands. However, a fraction prepared from dormant spore mitochondria by detergent extraction and (NH4)2SO4 fractionation contained readily detectable quantities of cytochromes c and b (as shown by the a and Soret absorption bands), but it did not contain the a or Soret bands of cytochrome a observed in a counterpart preparation from germinated spores. The pyridine hemochromogen preparation from the dormant spore mitochondria contained no material that is spectroscopically characteristic of a-type heme and protoheme. These results suggest that cytochrome a is not present as a functional molecule in dormant spores. The first spectroscopically detectable cytochromes were observed in whole mitochondria at 210 min of spore germination, and the amount of each of the cytochromes increased with cell growth. A precursor of the heme porphyrin, delta-[4-14C]aminolevulinic acid, was first incorporated (at accelerating rates) into acid-insoluble spore material at 180 min of germination, which appears to be the approximate time of organization of new mitochondria in these spores."}
{"id": "PMID:187570", "title": "Purification and characterization of cytochrome c3, ferredoxin, and rubredoxin isolated from Desulfovibrio desulfuricans Norway.", "content": "Different electron carriers of the non-desulfoviridin-containing, sulfate-reducing bacterium Desulfovibrio desulfuricans (Norway strain) have been studied. Two nonheme iron proteins, ferredoxin and rubredoxin, have been purified. This ferredoxin contains four atoms of non-heme iron and acid-labile sulfur and six residues of cysteine per molecule. Its amino acid composition suggests that it is homologous with the other Desulfovibrio ferredoxins. The rubredoxin is also an acidic protein of 6,000 molecular weight and contains one atom of iron and four cysteine residues per molecule. The amino acid composition and molecular weight of the cytochrome c3 from D. desulfuricans (strain Norway 4) are reported. Its spectral properties are very similar to those of the other cytochromes c3 (molecular weight, 13,000) of Desulfovibrio and show that it contains four hemes per molecule. This cytochrome has a very low redox potential and acts as a carrier in the coupling of hydrogenase and thiosulfate reductase in extracts of Desulfovibrio gigas and Desulfovibrio desulfuricans (Norway strain) in contrast to D. gigas cytochrome c3 (molecular weight, 13,000). A comparison of the activities of the cytochrome c3 (molecular weight, 13,000) of D. gigas and that of D. desulfuricans in this reaction suggests that these homologous proteins can have different specificity in the electron transfer chain of these bacteria.", "contents": "Purification and characterization of cytochrome c3, ferredoxin, and rubredoxin isolated from Desulfovibrio desulfuricans Norway. Different electron carriers of the non-desulfoviridin-containing, sulfate-reducing bacterium Desulfovibrio desulfuricans (Norway strain) have been studied. Two nonheme iron proteins, ferredoxin and rubredoxin, have been purified. This ferredoxin contains four atoms of non-heme iron and acid-labile sulfur and six residues of cysteine per molecule. Its amino acid composition suggests that it is homologous with the other Desulfovibrio ferredoxins. The rubredoxin is also an acidic protein of 6,000 molecular weight and contains one atom of iron and four cysteine residues per molecule. The amino acid composition and molecular weight of the cytochrome c3 from D. desulfuricans (strain Norway 4) are reported. Its spectral properties are very similar to those of the other cytochromes c3 (molecular weight, 13,000) of Desulfovibrio and show that it contains four hemes per molecule. This cytochrome has a very low redox potential and acts as a carrier in the coupling of hydrogenase and thiosulfate reductase in extracts of Desulfovibrio gigas and Desulfovibrio desulfuricans (Norway strain) in contrast to D. gigas cytochrome c3 (molecular weight, 13,000). A comparison of the activities of the cytochrome c3 (molecular weight, 13,000) of D. gigas and that of D. desulfuricans in this reaction suggests that these homologous proteins can have different specificity in the electron transfer chain of these bacteria."}
{"id": "PMID:187571", "title": "Specific deficit in the synthesis of 6-sulfoquinovsyl diglyceride in Chlorella pyrenoidosa.", "content": "It was found that when Chlorella pyrenoidosa was grown on cysteine as the sole sulfur source, it lost the ability to grow photoautotrophically. When grown in the presence of glucose, cysteine-grown cells displayed a doubling time in the light or dark of 45 h, which is identical to that of cells grown on glucose and SO4 in the dark. This suggests that cells grown on cysteine as sole sulfur source can only grow heterotrophically. In support of this hypothesis, it was found that cysteine-grown cells were defective both in vivo and in vitro in CO2 fixation, although O2 evolution in such cells was normal. Assays of the enzymes of the Calvin cycle indicated that the deficit in CO2 fixation could be ascribed to a lowered phosphoribulokinase activity. A total lipid analysis of Chlorella grown on cysteine revealed that such cells showed a 100-fold deficiency in the purportedly chloroplast-associated 6-sulfoquinovsyl diglyceride. This agrees with earlier reports that cysteine could not serve as a precursor of sulfolipid in Chlorella. No other polar lipid was affected. Large amounts of triglyceride, however, were found in cysteine-grown cells. The biosynthesis of triglyceride provides a means of utilizing reduced nicotinamide adenine dinucleotide reducing equivalents not being used for CO2 fixation.", "contents": "Specific deficit in the synthesis of 6-sulfoquinovsyl diglyceride in Chlorella pyrenoidosa. It was found that when Chlorella pyrenoidosa was grown on cysteine as the sole sulfur source, it lost the ability to grow photoautotrophically. When grown in the presence of glucose, cysteine-grown cells displayed a doubling time in the light or dark of 45 h, which is identical to that of cells grown on glucose and SO4 in the dark. This suggests that cells grown on cysteine as sole sulfur source can only grow heterotrophically. In support of this hypothesis, it was found that cysteine-grown cells were defective both in vivo and in vitro in CO2 fixation, although O2 evolution in such cells was normal. Assays of the enzymes of the Calvin cycle indicated that the deficit in CO2 fixation could be ascribed to a lowered phosphoribulokinase activity. A total lipid analysis of Chlorella grown on cysteine revealed that such cells showed a 100-fold deficiency in the purportedly chloroplast-associated 6-sulfoquinovsyl diglyceride. This agrees with earlier reports that cysteine could not serve as a precursor of sulfolipid in Chlorella. No other polar lipid was affected. Large amounts of triglyceride, however, were found in cysteine-grown cells. The biosynthesis of triglyceride provides a means of utilizing reduced nicotinamide adenine dinucleotide reducing equivalents not being used for CO2 fixation."}
{"id": "PMID:187572", "title": "Presence of cytochrome c in Desulfomonas pigra.", "content": "Desulfomonas pigra, a gram-negative, nonmotile anaerobic, sulfate-reducing bacillus isolated from human feces, was found to have cytochrome c and a desulfoviridin-like pigment.", "contents": "Presence of cytochrome c in Desulfomonas pigra. Desulfomonas pigra, a gram-negative, nonmotile anaerobic, sulfate-reducing bacillus isolated from human feces, was found to have cytochrome c and a desulfoviridin-like pigment."}
{"id": "PMID:187573", "title": "Internally generated reduced nicotinamide adenine dinucleotide as a substrate for glycine transport by membrane vesicles of Paracoccus denitrificans.", "content": "Internally generated reduced nicotinamide adenine dinucleotide was the most efficient substrate for glycine transport by membrane vesicles of Paracoccus denitrificans.", "contents": "Internally generated reduced nicotinamide adenine dinucleotide as a substrate for glycine transport by membrane vesicles of Paracoccus denitrificans. Internally generated reduced nicotinamide adenine dinucleotide was the most efficient substrate for glycine transport by membrane vesicles of Paracoccus denitrificans."}
{"id": "PMID:187574", "title": "Role of the rel gene product in the control of cyclic adenosine 3',5'-monophosphate accumulation.", "content": "The presence of a relA mutant allele affects the kinetics of cyclic adenosine 3',5'-monophosphate accumulation during downshift from glucose to succinate. The nucleotide accumulates at the normal rate early in the downshift transition but continues to accumulate for a longer time in the relA mutant, leading to a two- to threefold excess by the end of the diauxic lag. Evidence is presented that this effect occurs independently of the accumulation of ppGpp.", "contents": "Role of the rel gene product in the control of cyclic adenosine 3',5'-monophosphate accumulation. The presence of a relA mutant allele affects the kinetics of cyclic adenosine 3',5'-monophosphate accumulation during downshift from glucose to succinate. The nucleotide accumulates at the normal rate early in the downshift transition but continues to accumulate for a longer time in the relA mutant, leading to a two- to threefold excess by the end of the diauxic lag. Evidence is presented that this effect occurs independently of the accumulation of ppGpp."}
{"id": "PMID:187575", "title": "Cyclic adenosine 3',5'-monophosphate levels and activities of adenylate cyclase and cyclic adenosine 3',5'-monophosphate phosphodiesterase in Pseudomonas and Bacteroides.", "content": "A modified Gilman assay was used to determine the concentrations of cyclic adenosine 3',5'-monophosphate (cAMP) in rapidly filtered cells and in the culture filtrates of Pseudomonas aeruginosa, Escherichia coli K-12, and Bacteroides fragilis. In P. aeruginosa cultures, levels of cAMP in the filtrate increased with the culture absorbance (3.5 to 19.8 X 10(-9) M) but did not vary significantly with the carbon source used to support growth. Intracellular concentrations (0.8 to 3.2 X 10(-5) M) were substantially higher and did not vary appreciably during growth or with carbon source. Sodium cAMP (5 mM) failed to reverse the catabolite repression of inducible glucose-6-phosphate dehydrogenase (EC 1.1.1.49) synthesis caused by the addition of 10 mM succinate. Exogenous cAMP also had no discernible effect on the catabolite repression control of inducible mannitol dehydrogenase (EC 1.1.1.67). P. aeruginosa was found to contain both soluble cAMP phosphodiesterase (EC 3.1.4.17) and membrane-associated adenylate cyclase (EC 4.6.1.1) activity, and these were compared to the activities detected in crude extracts of E. coli. B. fragilis crude cell extracts contain neither of these enzyme activities, and little or no cAMP was detected in cells or culture filtrates of this anaerobic bacterium.", "contents": "Cyclic adenosine 3',5'-monophosphate levels and activities of adenylate cyclase and cyclic adenosine 3',5'-monophosphate phosphodiesterase in Pseudomonas and Bacteroides. A modified Gilman assay was used to determine the concentrations of cyclic adenosine 3',5'-monophosphate (cAMP) in rapidly filtered cells and in the culture filtrates of Pseudomonas aeruginosa, Escherichia coli K-12, and Bacteroides fragilis. In P. aeruginosa cultures, levels of cAMP in the filtrate increased with the culture absorbance (3.5 to 19.8 X 10(-9) M) but did not vary significantly with the carbon source used to support growth. Intracellular concentrations (0.8 to 3.2 X 10(-5) M) were substantially higher and did not vary appreciably during growth or with carbon source. Sodium cAMP (5 mM) failed to reverse the catabolite repression of inducible glucose-6-phosphate dehydrogenase (EC 1.1.1.49) synthesis caused by the addition of 10 mM succinate. Exogenous cAMP also had no discernible effect on the catabolite repression control of inducible mannitol dehydrogenase (EC 1.1.1.67). P. aeruginosa was found to contain both soluble cAMP phosphodiesterase (EC 3.1.4.17) and membrane-associated adenylate cyclase (EC 4.6.1.1) activity, and these were compared to the activities detected in crude extracts of E. coli. B. fragilis crude cell extracts contain neither of these enzyme activities, and little or no cAMP was detected in cells or culture filtrates of this anaerobic bacterium."}
{"id": "PMID:187576", "title": "Characterization of one neutral and two acidic glycoasparagines isolated from the urine of patients with aspartylglycosylaminuria (AGU).", "content": "One neutral and two acidic glycoasparagines were isolated from the urine of patients with aspartylglycosylaminuria (AGU). The neutral one was identified as beta-Gal-(1 leads to 4)-beta-GlcNAc-Asn. The acidic ones were composed of 1 mole of sialic acid and 2 moles each of galactose and N-acetylglucosamine, attached to asparagine, and were isomeric with respect to the position of sialic acid attachment since they produced the same glycoasparagine on incubation with the neuraminidase [EC 3.2.1.18] from Clostridium perfringens. The structure of the resulting sialic acid-free glycoasparagine was determined to be beta-Gal-beta-GlcNAc-beta-Gal-(1 leads to 4)-beta-GlcNAc-Asn based mainly on the results of sequential enzymatic degradations.", "contents": "Characterization of one neutral and two acidic glycoasparagines isolated from the urine of patients with aspartylglycosylaminuria (AGU). One neutral and two acidic glycoasparagines were isolated from the urine of patients with aspartylglycosylaminuria (AGU). The neutral one was identified as beta-Gal-(1 leads to 4)-beta-GlcNAc-Asn. The acidic ones were composed of 1 mole of sialic acid and 2 moles each of galactose and N-acetylglucosamine, attached to asparagine, and were isomeric with respect to the position of sialic acid attachment since they produced the same glycoasparagine on incubation with the neuraminidase [EC 3.2.1.18] from Clostridium perfringens. The structure of the resulting sialic acid-free glycoasparagine was determined to be beta-Gal-beta-GlcNAc-beta-Gal-(1 leads to 4)-beta-GlcNAc-Asn based mainly on the results of sequential enzymatic degradations."}
{"id": "PMID:187577", "title": "Generation of the superoxide radical during autoxidation of oxymyoglobin.", "content": "Autoxidation of bovine oxymyoglobin to metmyoglobin induces co-oxidation of epinephrine to adrenochrome. This co-oxidation is markedly inhibited by superoxide dismutase [EC 1.15.1.1]. Electron transfer from oxymyoglobin to ferricytochrome c is partially inhibited by superoxide dismutase. These results indicate that autoxidation of oxymyoglobin results in generation of superoxide radicals. Autoxidation of oxymyoglobin is accelerated by superoxide dismutase and partially inhibited by catalase [EC 1.11.1.6].", "contents": "Generation of the superoxide radical during autoxidation of oxymyoglobin. Autoxidation of bovine oxymyoglobin to metmyoglobin induces co-oxidation of epinephrine to adrenochrome. This co-oxidation is markedly inhibited by superoxide dismutase [EC 1.15.1.1]. Electron transfer from oxymyoglobin to ferricytochrome c is partially inhibited by superoxide dismutase. These results indicate that autoxidation of oxymyoglobin results in generation of superoxide radicals. Autoxidation of oxymyoglobin is accelerated by superoxide dismutase and partially inhibited by catalase [EC 1.11.1.6]."}
{"id": "PMID:187578", "title": "Conformational transitioons of polypeptide chain elongation factor Tu. II. Further studies by electron spin resonance.", "content": "The conformational transitions of polypeptide chain elongation factor Tu (EF-Tu) associated with the ligand change from GDP to GTP and also with the displacement of GDP by elongation factor Ts (EF-Ts) have been investigated using the spin-labeling technique. Of the two reactive sulfhydryl groups in EF-Tu, the one essential for interaction with aminoacyl-tRNA was selectively labeled with various kinds of iodoacetamide or maleimide spin-labeling reagents. The electron spin resonance (ESR) spectra of EF-Tu-GDP labeled with these reagents generally consisted of two components, one narrow and one broad, corresponding to labels relatively weakly and strongly immobilized, respectively. The degree of immobilization and the ratio of the narrow to the broad components were different for each kind of label used. The spectra of spin-labeled EF-Tu-GDP changed markedly when its GDP moiety was replaced by GTP through incubation with phosphoenolpyruvate and pyruvate kinase [EC 2.7.1.40], the broad component increasing at the expense of the narrow component. The reversible nature of the conformational change was confirmed with EF-Tu labeled with a maleimide reagent. The GTP-induced spectral change was reversed upon conversion of labeled EF-Tu-GTP to EF-Tu-GDP by addition of excess GDP. A similar type of spectral change was also observed when spin-labeled EF-Tu-GDP was incubated with EF-Ts to form labeled EF-Tu-EF-Ts complex. The extent of the spectral change induced by EF-Ts was even greater than that induced by GTP. These results, together with those obtained by studies with hydrophobic and fluorescent probes (Arai, Arai, Kawakita, & Kaziro (1975) J. Biochem. 77, 1095-1106) indicate that a reversible conformational change is induced in EF-Tu near the sulfhydryl group that is essential for interaction with aminoacyl-tRNA.", "contents": "Conformational transitioons of polypeptide chain elongation factor Tu. II. Further studies by electron spin resonance. The conformational transitions of polypeptide chain elongation factor Tu (EF-Tu) associated with the ligand change from GDP to GTP and also with the displacement of GDP by elongation factor Ts (EF-Ts) have been investigated using the spin-labeling technique. Of the two reactive sulfhydryl groups in EF-Tu, the one essential for interaction with aminoacyl-tRNA was selectively labeled with various kinds of iodoacetamide or maleimide spin-labeling reagents. The electron spin resonance (ESR) spectra of EF-Tu-GDP labeled with these reagents generally consisted of two components, one narrow and one broad, corresponding to labels relatively weakly and strongly immobilized, respectively. The degree of immobilization and the ratio of the narrow to the broad components were different for each kind of label used. The spectra of spin-labeled EF-Tu-GDP changed markedly when its GDP moiety was replaced by GTP through incubation with phosphoenolpyruvate and pyruvate kinase [EC 2.7.1.40], the broad component increasing at the expense of the narrow component. The reversible nature of the conformational change was confirmed with EF-Tu labeled with a maleimide reagent. The GTP-induced spectral change was reversed upon conversion of labeled EF-Tu-GTP to EF-Tu-GDP by addition of excess GDP. A similar type of spectral change was also observed when spin-labeled EF-Tu-GDP was incubated with EF-Ts to form labeled EF-Tu-EF-Ts complex. The extent of the spectral change induced by EF-Ts was even greater than that induced by GTP. These results, together with those obtained by studies with hydrophobic and fluorescent probes (Arai, Arai, Kawakita, & Kaziro (1975) J. Biochem. 77, 1095-1106) indicate that a reversible conformational change is induced in EF-Tu near the sulfhydryl group that is essential for interaction with aminoacyl-tRNA."}
{"id": "PMID:187579", "title": "Conformational transition of polypeptide chain elongation factor G as determined by electron spin resonance.", "content": "The conformational transition of the polypeptide chain elongation factor G (EF-G) induced by interaction with guanine nucleotide has been investigated by means of the spin-labeling technique. Various spin-label probes were attached specifically to the sulfhydryl group of the protein that is essential for binding to ribosomes, and the effects of these ligands on the electron spin resonance (ESR) spectra were examined. It was found that the ESR spectra of EF-G labeled with nitroxide maleimide reagents were modified by the addition of various guanine nucleotides such as GDP, GTP and, to a lesser extent, by Gpp(NH)p and Gpp(CH2)p, indicating that conformational changes accompany the binding of nucleotide ligand. However, the ESR spectra of labeled EF-G-GDP and EF-G-GTP were almost identical. On the other hand, when EF-G was labeled with nitroxide iodoacetamide reagents, a clear difference in the ESR spectra of EF-G-GDP and EF-G-GTP derivatives was observed. In this case, the spectral shape of the spin-labeled EF-G in the presence of GTP or its analogs, Gpp(NH)p or Gpp(CH2)p, was quite similar to that of free, unliganded EF-G derivative. These results, together with those previously obtained using hydrophobic probes (Arai, Arai, & Kaziro (1975) J. Biochem. 78, 243-246) demonstrate the existence of an EF-G-guanine nucleotide binary complex. They also indicate that there is a substantial difference in conformation between free EF-G, EF-G-GDP, and EF-G-GTP near the active site essential for interaction with ribosomes.", "contents": "Conformational transition of polypeptide chain elongation factor G as determined by electron spin resonance. The conformational transition of the polypeptide chain elongation factor G (EF-G) induced by interaction with guanine nucleotide has been investigated by means of the spin-labeling technique. Various spin-label probes were attached specifically to the sulfhydryl group of the protein that is essential for binding to ribosomes, and the effects of these ligands on the electron spin resonance (ESR) spectra were examined. It was found that the ESR spectra of EF-G labeled with nitroxide maleimide reagents were modified by the addition of various guanine nucleotides such as GDP, GTP and, to a lesser extent, by Gpp(NH)p and Gpp(CH2)p, indicating that conformational changes accompany the binding of nucleotide ligand. However, the ESR spectra of labeled EF-G-GDP and EF-G-GTP were almost identical. On the other hand, when EF-G was labeled with nitroxide iodoacetamide reagents, a clear difference in the ESR spectra of EF-G-GDP and EF-G-GTP derivatives was observed. In this case, the spectral shape of the spin-labeled EF-G in the presence of GTP or its analogs, Gpp(NH)p or Gpp(CH2)p, was quite similar to that of free, unliganded EF-G derivative. These results, together with those previously obtained using hydrophobic probes (Arai, Arai, & Kaziro (1975) J. Biochem. 78, 243-246) demonstrate the existence of an EF-G-guanine nucleotide binary complex. They also indicate that there is a substantial difference in conformation between free EF-G, EF-G-GDP, and EF-G-GTP near the active site essential for interaction with ribosomes."}
{"id": "PMID:187580", "title": "Studies on the turnover rates of ornithine aminotransferase in Morris hepatoma 44 and host liver.", "content": "The ornithine aminotransferase [EC 2.6.1.13] content of Morris hepatoma 44 is about 15 times higher than that in normal liver. The turnover rates of ornithine amino-transferase in hepatoma 44 and host liver were determined using L-[14C]leucine. Studies on the incorporation of radioactive leucine into ornithine aminotransferase in rats bearing hepatoma 44 showed that the rate of synthesis of this enzyme in the hepatoma was about 5-fold higher than that in host liver. The half-life of ornithine aminotransferase in host liver was 0.98 day, which was the same as that in normal liver, whereas that in hepatoma 44 was 3.5 days. The rate constant of degradation of ornithine aminotransferase in hepatoma 44 was significantly less than that in host liver. These results show that the high ornithine aminotransferase content of hepatoma 44 is due to both increase in its rate of synthesis and decrease in its rate of degradation.", "contents": "Studies on the turnover rates of ornithine aminotransferase in Morris hepatoma 44 and host liver. The ornithine aminotransferase [EC 2.6.1.13] content of Morris hepatoma 44 is about 15 times higher than that in normal liver. The turnover rates of ornithine amino-transferase in hepatoma 44 and host liver were determined using L-[14C]leucine. Studies on the incorporation of radioactive leucine into ornithine aminotransferase in rats bearing hepatoma 44 showed that the rate of synthesis of this enzyme in the hepatoma was about 5-fold higher than that in host liver. The half-life of ornithine aminotransferase in host liver was 0.98 day, which was the same as that in normal liver, whereas that in hepatoma 44 was 3.5 days. The rate constant of degradation of ornithine aminotransferase in hepatoma 44 was significantly less than that in host liver. These results show that the high ornithine aminotransferase content of hepatoma 44 is due to both increase in its rate of synthesis and decrease in its rate of degradation."}
{"id": "PMID:187581", "title": "The role of tryptophanyl residues in heavy meromyosin as studied by chemical modification with 2-hydroxy-5-nitrobenzyl bromide.", "content": "1. Two moles of 2-hydroxy-5-nitrobenzyl group bound selectively to one mole of heavy meromyosin when it was treated with 2-hydroxy-5-nitrobenzyl bromide, a specific reagent for tryptophanyl residues. The binding with ADP, the size of the initial burst of Pi liberation and the difference absorption spectrum with and without ADP of the bound 2-hydroxy-5-nitrobenzyl groups were measured with heavy meromyosin modified with various amounts of reagent. The properties of the modified heavy meromyosin did not change until the molar binding ratio of the reagent, rH, was about 1, but the properties changed remarkably when rH increased from 1 to 2. 2. Subfragment-1 was prepared from the modified heavy meromyosin by trypsin [EC 3.4.21.4] digestion. The molar binding ratio of the reagent in subfragment-1, rS, was found to be less than 0.1 when rH of the starting heavy meromyosin was less than 0.8. However, rS was about 0.5 in subfragment-1 prepared from heavy meromyosin of rH about 2. The results indicate that only one mole of 2-hydroxy-5-nitrobenzyl group, which was bound with lower reactivity than the other, was bound to a head part of heavy meromyosin. 3. Subfragment-1 fraction prepared from the modified heavy meromyosin could be separated into two fractions by DE-32 cellulose column chromatography; the subfragment-1 portion which eluted later showed a higher rS than that eluted in front. The binding with ADP, the size of the initial burst of Pi liberation and the difference absorption spectrum induced by ATP were measured with the modified subfragment-1 separated by DE-32 cellulose column chromatography. The ADP-binding ability and the size of the initial burst were not dependent on rS, and coincided with those of subfragment-1 prepared from unmodified heavy meromyosin. 4. The results of ADP binding studies suggest that heavy meromyosin is constituted from nonidentical subunits, and that there is an interaction between them which controls the ADP binding. Two tryptophanyl residues having specific reactivity toward 2-hydroxy-5-nitrobenzyl bromide are assumed to be involved in the interaction.", "contents": "The role of tryptophanyl residues in heavy meromyosin as studied by chemical modification with 2-hydroxy-5-nitrobenzyl bromide. 1. Two moles of 2-hydroxy-5-nitrobenzyl group bound selectively to one mole of heavy meromyosin when it was treated with 2-hydroxy-5-nitrobenzyl bromide, a specific reagent for tryptophanyl residues. The binding with ADP, the size of the initial burst of Pi liberation and the difference absorption spectrum with and without ADP of the bound 2-hydroxy-5-nitrobenzyl groups were measured with heavy meromyosin modified with various amounts of reagent. The properties of the modified heavy meromyosin did not change until the molar binding ratio of the reagent, rH, was about 1, but the properties changed remarkably when rH increased from 1 to 2. 2. Subfragment-1 was prepared from the modified heavy meromyosin by trypsin [EC 3.4.21.4] digestion. The molar binding ratio of the reagent in subfragment-1, rS, was found to be less than 0.1 when rH of the starting heavy meromyosin was less than 0.8. However, rS was about 0.5 in subfragment-1 prepared from heavy meromyosin of rH about 2. The results indicate that only one mole of 2-hydroxy-5-nitrobenzyl group, which was bound with lower reactivity than the other, was bound to a head part of heavy meromyosin. 3. Subfragment-1 fraction prepared from the modified heavy meromyosin could be separated into two fractions by DE-32 cellulose column chromatography; the subfragment-1 portion which eluted later showed a higher rS than that eluted in front. The binding with ADP, the size of the initial burst of Pi liberation and the difference absorption spectrum induced by ATP were measured with the modified subfragment-1 separated by DE-32 cellulose column chromatography. The ADP-binding ability and the size of the initial burst were not dependent on rS, and coincided with those of subfragment-1 prepared from unmodified heavy meromyosin. 4. The results of ADP binding studies suggest that heavy meromyosin is constituted from nonidentical subunits, and that there is an interaction between them which controls the ADP binding. Two tryptophanyl residues having specific reactivity toward 2-hydroxy-5-nitrobenzyl bromide are assumed to be involved in the interaction."}
{"id": "PMID:187582", "title": "The isolation and characterization of glycopeptides and mucopolysaccharides from plasma membranes of an ascites hepatoma, AH 130 FN.", "content": "Plasma membranes were isolated from an ascites hepatoma, AH 130 FN, a free-cell type subline of AH 130, by the fluorescein mercuric acetate (FMA) method. Glycopeptides and mucopolysaccharides were prepared from the membranes by pronase digestion then fractionated chromatographically and electrophoretically. Isolated fractions were analyzed for amino acid and carbohydrate compositions. The results were compared with those for corresponding fractions from AH 66 and AH 130 ((1974) J. Biochem. 76, 319-333; (1975) ibid., 78, 863-872). The fraction excluded from Sephadex G-50 contained mucopolysaccharides and a series of glycopeptides. The mucopolysaccharides were identified as chondroitin sulfate A on the basis of their chemical composition, electrophoretic behavior on cellulose acetate and digestibility with chondroitinase AC [EC 4.2.2.5]. This contrasts with previous findings that mucopolysaccharides from the corresponding fractions from AH 130 and AH 66 were heparan sulfate. The chemical composition of the glycopeptides, which showed high contents of threonine, serine, galactose, galactosamine, glucosamine, and sialic acid, indicated the presence of glycopeptides with O-glycosidic linkages. The glycopeptides also contained a small but significant amount of aspartic acid, suggesting that N-glycosidic glycopeptides were also contained in this fraction. The fraction included in Sepnadex G-50 contaoned N-glycosidic glycopeptides as major components, since the carbohydrate moieties were composed of fucose, galactose, mannose, glucosamine, sialic acid, and a smaller amount of galactosamine. The presence of galactosamine suggested that O-glycosidic glycopeptides were present as minor components. Glycopeptides with both O- and N-glycosidic linkages were isolated from AH 130, but not from AH 66.", "contents": "The isolation and characterization of glycopeptides and mucopolysaccharides from plasma membranes of an ascites hepatoma, AH 130 FN. Plasma membranes were isolated from an ascites hepatoma, AH 130 FN, a free-cell type subline of AH 130, by the fluorescein mercuric acetate (FMA) method. Glycopeptides and mucopolysaccharides were prepared from the membranes by pronase digestion then fractionated chromatographically and electrophoretically. Isolated fractions were analyzed for amino acid and carbohydrate compositions. The results were compared with those for corresponding fractions from AH 66 and AH 130 ((1974) J. Biochem. 76, 319-333; (1975) ibid., 78, 863-872). The fraction excluded from Sephadex G-50 contained mucopolysaccharides and a series of glycopeptides. The mucopolysaccharides were identified as chondroitin sulfate A on the basis of their chemical composition, electrophoretic behavior on cellulose acetate and digestibility with chondroitinase AC [EC 4.2.2.5]. This contrasts with previous findings that mucopolysaccharides from the corresponding fractions from AH 130 and AH 66 were heparan sulfate. The chemical composition of the glycopeptides, which showed high contents of threonine, serine, galactose, galactosamine, glucosamine, and sialic acid, indicated the presence of glycopeptides with O-glycosidic linkages. The glycopeptides also contained a small but significant amount of aspartic acid, suggesting that N-glycosidic glycopeptides were also contained in this fraction. The fraction included in Sepnadex G-50 contaoned N-glycosidic glycopeptides as major components, since the carbohydrate moieties were composed of fucose, galactose, mannose, glucosamine, sialic acid, and a smaller amount of galactosamine. The presence of galactosamine suggested that O-glycosidic glycopeptides were present as minor components. Glycopeptides with both O- and N-glycosidic linkages were isolated from AH 130, but not from AH 66."}
{"id": "PMID:187583", "title": "Evidence for the presence of di- and triphospho pyridine nucleotide dehydrogenase derivatives as consistent contaminants of purified beef heart cytochrome-c oxidase.", "content": "Purified beef heart cytochrome-c oxidase preparations derived by three different laboratories contain NADH-K3 Fe (CN)6, NADH-nitrobluetetrazolium, and NADPH-nitrobluetetrazolium reductases. This is true of preparations exhibiting heme aa3 to protein ratios considered indicative of an excellent purity. An apparent association of cytochrome-c oxidase and one or more of the contaminants persists through immunodiffusion and nondenaturing electrophoresis and, in addition, in one instance copurification of NADH-K3Fe(CN)6 reductase and cytochrome-c oxidase to a constant ratio of specific activities was demonstrated. Cytochrome-c oxidase can be freed of the contaminants by equilibration with an NAD+-affinity matrix. As aconcomitant of equilibration with the matrix, the KM of cytochrome-c oxidase for ferrocytochrome-c is invariably decreased. Rat constants at low ferrocytochrome-c concentrations are consistently enhanced in all oxidase preparations upon equilibration with the NAD+ matrix. However, the effects of such equilibrations on the extrapolated Vmax varies from one preparation to another. Polyacrylamide gel electrophoresis in SDS-urea systems establishes that each of the preparations contains a minimum of three contaminants, each of an apparent formula weight of greater than 40,000 Daltons. NADH-NBT reductase was found to have a formula weight of approximately 46,000 Daltons. Their properties establish that NADH-K3Fe(CN)6 and NADH-NBT reductases are separate proteins; the separate identity of NADPH-NBT reductase has not yet been determined.", "contents": "Evidence for the presence of di- and triphospho pyridine nucleotide dehydrogenase derivatives as consistent contaminants of purified beef heart cytochrome-c oxidase. Purified beef heart cytochrome-c oxidase preparations derived by three different laboratories contain NADH-K3 Fe (CN)6, NADH-nitrobluetetrazolium, and NADPH-nitrobluetetrazolium reductases. This is true of preparations exhibiting heme aa3 to protein ratios considered indicative of an excellent purity. An apparent association of cytochrome-c oxidase and one or more of the contaminants persists through immunodiffusion and nondenaturing electrophoresis and, in addition, in one instance copurification of NADH-K3Fe(CN)6 reductase and cytochrome-c oxidase to a constant ratio of specific activities was demonstrated. Cytochrome-c oxidase can be freed of the contaminants by equilibration with an NAD+-affinity matrix. As aconcomitant of equilibration with the matrix, the KM of cytochrome-c oxidase for ferrocytochrome-c is invariably decreased. Rat constants at low ferrocytochrome-c concentrations are consistently enhanced in all oxidase preparations upon equilibration with the NAD+ matrix. However, the effects of such equilibrations on the extrapolated Vmax varies from one preparation to another. Polyacrylamide gel electrophoresis in SDS-urea systems establishes that each of the preparations contains a minimum of three contaminants, each of an apparent formula weight of greater than 40,000 Daltons. NADH-NBT reductase was found to have a formula weight of approximately 46,000 Daltons. Their properties establish that NADH-K3Fe(CN)6 and NADH-NBT reductases are separate proteins; the separate identity of NADPH-NBT reductase has not yet been determined."}
{"id": "PMID:187584", "title": "Chromatin receptors for thyroid hormones. Interactions of the solubilized proteins with DNA.", "content": "Thyroid hormone-responsive tissues contain chromatin \"receptor\" proteins that are concentrated in chromatin subfractions enriched in DNA. These receptors appear to be DNA-binding proteins. In the present study, we utilized a DNA-cellulose binding assay to further examine the interactions of solubilized receptors with DNA. [125I]Triiodothyronine associates with receptors bound to DNA-cellulose, whereas free [I]triiodothyronine and [125I]triiodothyronine associated with other proteins does not. The DNA-receptor interactions appear to be strong enough to exist at physiological ionic strength since binding is 50% maximal ag 0.175 M NaCl and is only partly inhibited by Ca2+ and Mg2+ in the 1 to 5 mM range. Most, if not all, of the receptors are capable of DNA binding, and there are at least 80,000 receptor binding sites/diploid DNA (assuming one triiodothyronine binding site/receptor). Binding of the receptor-[125I]triiodothyronine complexes to other DNAs and analogs was examined using a competition assay. There is similar binding by native and denatured DNA, gy eukaryotic DNA from different species and by prokaryotic DNA (Bacillus subtilis). Binding by natural DNAs is more avid than by cytoplasmic RNA, nuclear RNA, poly(dA-dT)-poly(dA-dT), or poly(dG-dC)-poly(dG-dC). Under these conditions, binding by tRNA and poly(dA) is insignificant, and the nucleotide monomers ATP and GTP have no detectable binding. These studies support the idea that the thyroid hormone receptor is a DNA-binding protein and that the interaction is a major determinant for receptor localization in chromatin. The competition studies suggest that the polynucleotide composition and/or conformation can have marked influences on the binding, and that multiple orders of binding affinity can exist. The presence of specific sequences cannot be excluded. However, the finding that receptors bind extensively and tightly to DNA suggests that receptors in chromatin may randomly bind to any available DNA, resulting in some of the receptors being at physiologically unimportant sites. If so, the several thousand hormone receptors present in each target cell may be required to enhance the possibility that some of the receptors are present at the actual sites of action.", "contents": "Chromatin receptors for thyroid hormones. Interactions of the solubilized proteins with DNA. Thyroid hormone-responsive tissues contain chromatin \"receptor\" proteins that are concentrated in chromatin subfractions enriched in DNA. These receptors appear to be DNA-binding proteins. In the present study, we utilized a DNA-cellulose binding assay to further examine the interactions of solubilized receptors with DNA. [125I]Triiodothyronine associates with receptors bound to DNA-cellulose, whereas free [I]triiodothyronine and [125I]triiodothyronine associated with other proteins does not. The DNA-receptor interactions appear to be strong enough to exist at physiological ionic strength since binding is 50% maximal ag 0.175 M NaCl and is only partly inhibited by Ca2+ and Mg2+ in the 1 to 5 mM range. Most, if not all, of the receptors are capable of DNA binding, and there are at least 80,000 receptor binding sites/diploid DNA (assuming one triiodothyronine binding site/receptor). Binding of the receptor-[125I]triiodothyronine complexes to other DNAs and analogs was examined using a competition assay. There is similar binding by native and denatured DNA, gy eukaryotic DNA from different species and by prokaryotic DNA (Bacillus subtilis). Binding by natural DNAs is more avid than by cytoplasmic RNA, nuclear RNA, poly(dA-dT)-poly(dA-dT), or poly(dG-dC)-poly(dG-dC). Under these conditions, binding by tRNA and poly(dA) is insignificant, and the nucleotide monomers ATP and GTP have no detectable binding. These studies support the idea that the thyroid hormone receptor is a DNA-binding protein and that the interaction is a major determinant for receptor localization in chromatin. The competition studies suggest that the polynucleotide composition and/or conformation can have marked influences on the binding, and that multiple orders of binding affinity can exist. The presence of specific sequences cannot be excluded. However, the finding that receptors bind extensively and tightly to DNA suggests that receptors in chromatin may randomly bind to any available DNA, resulting in some of the receptors being at physiologically unimportant sites. If so, the several thousand hormone receptors present in each target cell may be required to enhance the possibility that some of the receptors are present at the actual sites of action."}
{"id": "PMID:187585", "title": "Gonadotropin receptors in plasma membranes of bovine corpus luteum. I. Effect of phospholipases on the binding of 125I-choriogonadotropin by membrane-associated and solubilized receptors.", "content": "The ability of bovine corpus luteum plasma membranes to bind 125I-choriogonadotropin has been examined after prior treatment of the membranes with phospholipases A, C, and D. Treatment of the purified membranes with low concentrations of phospholipases A and C resulted in the inhibition of the binding of 125I-choriogonadotropin to its receptors, whereas phospholipase D had no effect. Receptor activity was decreased by low concentrations of phospholipase A from either bee venom, Vipera russelli or Crotalus terrificus terrificus. Similarly, low concentrations of phospholipase C from Clostridium perfringens and Clostridium welchii also inhibited the binding activity while comparatively higher concentrations of phospholipase C from Bacillus cereus were required to achieve comparable inhibition. The time required to produce 50% inhibition of in vitro binding by phospholipases A and C was found to be 6 and 23 min, respectively. Upon either removal or chelation of calcium ions by ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) both enzymes were completely inhibited as evidenced by the complete retention of the membrane binding activity. The decrease in the specific binding of choriogonadotropin to membranes after phospholipase digestion resulted in a decrease in the number of binding sites and was not accompanied by a change in the affinity of the hormone-receptor complex. The rates of association and dissociation of the 125I-choriogonadotropin-receptor complex and the equilibrium dissociation constant (Kd) were nearly identical in untreated and phospholipase-treated membranes. Phospholipases did not have any effect on the preformed hormone-receptor complex or on solubilized receptor. Filtration through Sepharose 6B of solubilized 125I-choriogonadotropin-receptor complex from untreated membranes or membranes which had been pretreated with phospholipase C prior to carrying out hormone binding did not alter the profile (Kav 0.38). Gel filtration of membranes treated with phospholipase A showed two peaks of bound radioactivity with distribution coefficients (Kav) of 0.08 and 0.35, respectively.", "contents": "Gonadotropin receptors in plasma membranes of bovine corpus luteum. I. Effect of phospholipases on the binding of 125I-choriogonadotropin by membrane-associated and solubilized receptors. The ability of bovine corpus luteum plasma membranes to bind 125I-choriogonadotropin has been examined after prior treatment of the membranes with phospholipases A, C, and D. Treatment of the purified membranes with low concentrations of phospholipases A and C resulted in the inhibition of the binding of 125I-choriogonadotropin to its receptors, whereas phospholipase D had no effect. Receptor activity was decreased by low concentrations of phospholipase A from either bee venom, Vipera russelli or Crotalus terrificus terrificus. Similarly, low concentrations of phospholipase C from Clostridium perfringens and Clostridium welchii also inhibited the binding activity while comparatively higher concentrations of phospholipase C from Bacillus cereus were required to achieve comparable inhibition. The time required to produce 50% inhibition of in vitro binding by phospholipases A and C was found to be 6 and 23 min, respectively. Upon either removal or chelation of calcium ions by ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) both enzymes were completely inhibited as evidenced by the complete retention of the membrane binding activity. The decrease in the specific binding of choriogonadotropin to membranes after phospholipase digestion resulted in a decrease in the number of binding sites and was not accompanied by a change in the affinity of the hormone-receptor complex. The rates of association and dissociation of the 125I-choriogonadotropin-receptor complex and the equilibrium dissociation constant (Kd) were nearly identical in untreated and phospholipase-treated membranes. Phospholipases did not have any effect on the preformed hormone-receptor complex or on solubilized receptor. Filtration through Sepharose 6B of solubilized 125I-choriogonadotropin-receptor complex from untreated membranes or membranes which had been pretreated with phospholipase C prior to carrying out hormone binding did not alter the profile (Kav 0.38). Gel filtration of membranes treated with phospholipase A showed two peaks of bound radioactivity with distribution coefficients (Kav) of 0.08 and 0.35, respectively."}
{"id": "PMID:187586", "title": "Gonadotropin receptors in plasma membranes of bovine corpus luteum. II. Role of membrane phospholipids.", "content": "The role of phospholipids in the binding of 125I-choriogonadotropin to bovine corpus luteum plasma membranes has been investigated with the use of purified phospholipase A and phospholipase C to alter membrane phospholipids. The phospholipase C-digested plasma membrane preparation showed 85 to 90% inhibition of 125I-choriogonadotropin binding activity when 70% of the membrane phospholipid was hydrolyzed. Similarly treatment of plasma membranes with phospholipase A resulted in 45 to 55% hydrolysis of membrane phospholipid and almost 75% inhibition of receptor activity. Both these enzymes hydrolyzed membrane-associated phosphatidylcholine to a greater extent than phosphatidylethanolamine and phosphatidylserine. Phosphorylaminoalcohols of phospholiphase C end products were completely released into the medium, while phospholipase A by-products remained associated with plasma membranes. Addition of a phospholipids suspension or liposomes to plasma membranes pretreated with phospholipase A and C did not restore gonadotropin binding activity. Soluble phosphorylcholine, phosphorylethanolamine, and phosphorylserine and insoluble diglyceride products of phospholipase C action had no effect on receptor activity. In contrast, end products of the phospholipase A action, such as lysophosphatides and fatty acids, inhibited both on the membrane-associated and solubilized receptor activity. Lysophosphatidylcholine was the most effective end product inhibiting the binding of gonadotropin to the receptor, followed by lysophosphatidylethanolamine and lysophosphatidylserine. The inhibitory effects of phospholipase A or lysophosphatides were completely reversed upon removal of membrane-bound phospholipid end products by washing the membranes with defatted bovine serum albumin. However, phospholipase C inhibition could not be overcome by defatted albumin washings. Solubilization of plasma membranes with detergents which had been pretreated with phospholipase C partially restored the inhibited activity. It is concluded that the phospholipase-mediated inhibition of gonadotropin binding activity was due to hydrolysis and alterations of the phospholipid environment in the case of phospholipase C and by direct inhibition by end products in the case of phospholipase A.", "contents": "Gonadotropin receptors in plasma membranes of bovine corpus luteum. II. Role of membrane phospholipids. The role of phospholipids in the binding of 125I-choriogonadotropin to bovine corpus luteum plasma membranes has been investigated with the use of purified phospholipase A and phospholipase C to alter membrane phospholipids. The phospholipase C-digested plasma membrane preparation showed 85 to 90% inhibition of 125I-choriogonadotropin binding activity when 70% of the membrane phospholipid was hydrolyzed. Similarly treatment of plasma membranes with phospholipase A resulted in 45 to 55% hydrolysis of membrane phospholipid and almost 75% inhibition of receptor activity. Both these enzymes hydrolyzed membrane-associated phosphatidylcholine to a greater extent than phosphatidylethanolamine and phosphatidylserine. Phosphorylaminoalcohols of phospholiphase C end products were completely released into the medium, while phospholipase A by-products remained associated with plasma membranes. Addition of a phospholipids suspension or liposomes to plasma membranes pretreated with phospholipase A and C did not restore gonadotropin binding activity. Soluble phosphorylcholine, phosphorylethanolamine, and phosphorylserine and insoluble diglyceride products of phospholipase C action had no effect on receptor activity. In contrast, end products of the phospholipase A action, such as lysophosphatides and fatty acids, inhibited both on the membrane-associated and solubilized receptor activity. Lysophosphatidylcholine was the most effective end product inhibiting the binding of gonadotropin to the receptor, followed by lysophosphatidylethanolamine and lysophosphatidylserine. The inhibitory effects of phospholipase A or lysophosphatides were completely reversed upon removal of membrane-bound phospholipid end products by washing the membranes with defatted bovine serum albumin. However, phospholipase C inhibition could not be overcome by defatted albumin washings. Solubilization of plasma membranes with detergents which had been pretreated with phospholipase C partially restored the inhibited activity. It is concluded that the phospholipase-mediated inhibition of gonadotropin binding activity was due to hydrolysis and alterations of the phospholipid environment in the case of phospholipase C and by direct inhibition by end products in the case of phospholipase A."}
{"id": "PMID:187587", "title": "Angiotensin II binding to mammalian brain membranes.", "content": "High affinity binding sites for angiotensin II in bovine and rat brain membranes have been identified and characterized using monoiodinated Ile5-angiotensin II of high specific radioactivity. Degradation of labeled and unlabeled peptide by washed brain particulate fractions was prevented by adding glucagon to the final incubation medium and including a proteolytic enzyme inhibitor (phenylmethylsulfonyl fluoride) in preincubation and incubation procedures. 125I-Angiotensin II binding can be studied using either centrifugation or filtration techniques to separate tissue-bound radioactivity. 125I-Angiotensin II binding to calf brain membranes is saturable and reversible, with a dissociation binding constant of 0.2 nM at 37 degrees. A similar binding constant is found in rat brain membranes. Analogues and fragments of angiotensin II compete for these brain binding sites with potencies which correlate with both their in vivo potencies and their binding inhibition protencies at adrenal cortex angiotensin II receptors. Angiotensin I is 1 to 2 orders of magnitude weaker than angiotensin II; the 3-8 hexapeptide and 4-8 pentapeptide are much weaker still. (desAsp1) angiotensin II (angiotensin III) is slightly more potent than angiotensin II, as are several antagonists of angiotensin II with aliphatic amino acids substituted at position 8. In calf brain 125I-angiotensin II binding is restricted almost exclusively to the cerebellum (cortex and deep nuclei). In rat brain, angiotensin II binding is highest in the thalamus-hypothalamus, midbrain, and brainstem, areas which are believed to be involved in mediating angiotensin II-induced central effects. These findings illustrate the presence of high affinity specific binding sites for angiotensin II in rat and bovine brain and suggest a physiological role for angiotensin peptides in the central nervous system.", "contents": "Angiotensin II binding to mammalian brain membranes. High affinity binding sites for angiotensin II in bovine and rat brain membranes have been identified and characterized using monoiodinated Ile5-angiotensin II of high specific radioactivity. Degradation of labeled and unlabeled peptide by washed brain particulate fractions was prevented by adding glucagon to the final incubation medium and including a proteolytic enzyme inhibitor (phenylmethylsulfonyl fluoride) in preincubation and incubation procedures. 125I-Angiotensin II binding can be studied using either centrifugation or filtration techniques to separate tissue-bound radioactivity. 125I-Angiotensin II binding to calf brain membranes is saturable and reversible, with a dissociation binding constant of 0.2 nM at 37 degrees. A similar binding constant is found in rat brain membranes. Analogues and fragments of angiotensin II compete for these brain binding sites with potencies which correlate with both their in vivo potencies and their binding inhibition protencies at adrenal cortex angiotensin II receptors. Angiotensin I is 1 to 2 orders of magnitude weaker than angiotensin II; the 3-8 hexapeptide and 4-8 pentapeptide are much weaker still. (desAsp1) angiotensin II (angiotensin III) is slightly more potent than angiotensin II, as are several antagonists of angiotensin II with aliphatic amino acids substituted at position 8. In calf brain 125I-angiotensin II binding is restricted almost exclusively to the cerebellum (cortex and deep nuclei). In rat brain, angiotensin II binding is highest in the thalamus-hypothalamus, midbrain, and brainstem, areas which are believed to be involved in mediating angiotensin II-induced central effects. These findings illustrate the presence of high affinity specific binding sites for angiotensin II in rat and bovine brain and suggest a physiological role for angiotensin peptides in the central nervous system."}
{"id": "PMID:187588", "title": "Spin-labeled stearates as probes for microenvironment of murine thymocyte adenylate cyclase-cyclic adenosine 3':5'-monophosphate system.", "content": "The interaction of various spin-labeled compounds with the murine thymocyte adenylate cyclase-cyclic AMP system was investigated. Electron paramagnetic resonance spectra from spin-labeled compounds were used to calculate the order parameter, S, and indicated that the thymocyte plasma membrane is a relatively rigid structure. Increasing concentrations of spin-labeled stearates, but not their corresponding methyl esters, resulted in increased membrane fluidity, partial lysis, and concomitant complete inhibition of cholera toxin-mediated increases in cyclic AMP content. Upon subsequent isolation of plasma membranes from these cells, cholera toxin-stimulated adenylate cyclase activity was also completely inhibited. Direct addition of spin-labeled stearates, but not spin-labeled methyl stearates, to thymocyte homogenates caused a dramatic reduction of basal, cholera toxin-, isoproterenol-, NaF-, and prostaglandin E1-stimulated adenylate cyclase activity. Inhibition was complete within the first minute of addition to homogenates and required approximately 0.2 mM spin-labeled stearate I(12,3) for half-maximal inhibition. This inhibition occurred in the presence or absence of an ATP-regenerating system and was not readily reversible. Furthermore, since the membrane cyclic phosphodiesterase activity was not altered by spin-labeled stearates, their inhibition was attributed to a direct action of stearate spin labels on adenylate cyclase. Neither stearate, methyl stearate, spin-labeled methyl stearates nor 2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempo) altered cell viability or enzyme activities at the concentrations studied. Spin-labeled stearates seemed to intercalate into different areas of the plasma membrane than their corresponding methyl esters. Furthermore, the action of spin-labeled stearates appeared to be on the exterior of the plasma membrane rather than the interior. These results illustrate the presence of multilipid domains and the importance of selected lipids and lipid-protein interactions in the adenylate cyclase-cyclic AMP system. Thymocyte adenylate cyclase is described in terms of a current model for membrane proteins.", "contents": "Spin-labeled stearates as probes for microenvironment of murine thymocyte adenylate cyclase-cyclic adenosine 3':5'-monophosphate system. The interaction of various spin-labeled compounds with the murine thymocyte adenylate cyclase-cyclic AMP system was investigated. Electron paramagnetic resonance spectra from spin-labeled compounds were used to calculate the order parameter, S, and indicated that the thymocyte plasma membrane is a relatively rigid structure. Increasing concentrations of spin-labeled stearates, but not their corresponding methyl esters, resulted in increased membrane fluidity, partial lysis, and concomitant complete inhibition of cholera toxin-mediated increases in cyclic AMP content. Upon subsequent isolation of plasma membranes from these cells, cholera toxin-stimulated adenylate cyclase activity was also completely inhibited. Direct addition of spin-labeled stearates, but not spin-labeled methyl stearates, to thymocyte homogenates caused a dramatic reduction of basal, cholera toxin-, isoproterenol-, NaF-, and prostaglandin E1-stimulated adenylate cyclase activity. Inhibition was complete within the first minute of addition to homogenates and required approximately 0.2 mM spin-labeled stearate I(12,3) for half-maximal inhibition. This inhibition occurred in the presence or absence of an ATP-regenerating system and was not readily reversible. Furthermore, since the membrane cyclic phosphodiesterase activity was not altered by spin-labeled stearates, their inhibition was attributed to a direct action of stearate spin labels on adenylate cyclase. Neither stearate, methyl stearate, spin-labeled methyl stearates nor 2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempo) altered cell viability or enzyme activities at the concentrations studied. Spin-labeled stearates seemed to intercalate into different areas of the plasma membrane than their corresponding methyl esters. Furthermore, the action of spin-labeled stearates appeared to be on the exterior of the plasma membrane rather than the interior. These results illustrate the presence of multilipid domains and the importance of selected lipids and lipid-protein interactions in the adenylate cyclase-cyclic AMP system. Thymocyte adenylate cyclase is described in terms of a current model for membrane proteins."}
{"id": "PMID:187589", "title": "On the nature of the three intermediate species formed after reaction of reduced cytochrome oxidase with oxygen.", "content": "Spectral examinations of the reaction of reduced cytochrome oxidase with molecular oxygen has revealed the formation of at least three intermediates, which are designated as Compounds I, II, and III according to the order of their appearance. From the difference spectrum against the oxidized oxidase, Compound I is characterized by a maximum at 605 nm, Compound II at 578 nm, and Compound III by double peaks at around 600 and 580 nm. In the Soret region, Compound I shows a peak at 435 nm and a trough at 412 nm, Compound III exhibits a peak at 442 to 443 nm and a trough at 418 nm. In the absence of cytochrome c, the spontaneous decay of Compound I precedes that of Compound II; the first order rate constants have been found to be 4 X 10(-3) s(-1) and 8 X 10(-4) s(-1) for Compounds I and II, respectively. Compound III, however, does not revert back to the oxidized form even after several hours. The decay of Compound I is accelerated in the presence of ferrocytochrome c by a factor of 10(3) to 10(4) depending on the concentration of the latter. The time for sequential differentiation between Compound I and Compound II becomes less clear in the presence than in the absence of ferrocytochrome c. On the contrary ferricytochrome c does not show such an accelerating effect. These and other observations lead us to postulate Compound I as an active intermediate, the true oxygenated compound in the cytocchrome oxidase reaction.", "contents": "On the nature of the three intermediate species formed after reaction of reduced cytochrome oxidase with oxygen. Spectral examinations of the reaction of reduced cytochrome oxidase with molecular oxygen has revealed the formation of at least three intermediates, which are designated as Compounds I, II, and III according to the order of their appearance. From the difference spectrum against the oxidized oxidase, Compound I is characterized by a maximum at 605 nm, Compound II at 578 nm, and Compound III by double peaks at around 600 and 580 nm. In the Soret region, Compound I shows a peak at 435 nm and a trough at 412 nm, Compound III exhibits a peak at 442 to 443 nm and a trough at 418 nm. In the absence of cytochrome c, the spontaneous decay of Compound I precedes that of Compound II; the first order rate constants have been found to be 4 X 10(-3) s(-1) and 8 X 10(-4) s(-1) for Compounds I and II, respectively. Compound III, however, does not revert back to the oxidized form even after several hours. The decay of Compound I is accelerated in the presence of ferrocytochrome c by a factor of 10(3) to 10(4) depending on the concentration of the latter. The time for sequential differentiation between Compound I and Compound II becomes less clear in the presence than in the absence of ferrocytochrome c. On the contrary ferricytochrome c does not show such an accelerating effect. These and other observations lead us to postulate Compound I as an active intermediate, the true oxygenated compound in the cytocchrome oxidase reaction."}
{"id": "PMID:187590", "title": "Platelet cyclic 3':5'-nucleotide phosphodiesterase released by thrombin and calcium ionophore.", "content": "Contact of rat platelets with thrombin or the divalent cation ionophore A-23187, in the presence of extracellular calcium, resulted in the secretion of adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP) phosphodiesterases. Significant association of calcium with platelets occurred during platelet surface contact with thrombin. Thrombin concentration to induce association of calcium virtually agreed with that to release the enzyme. The finding that A-23187 (5 to 20 muM) also provoked a rapid and marked association of extracellular calcium with platelets suggests that calcium mobilization into the intracellular environment may account, at least in part, for this association between platelet and calcium. Two different phosphodiesterases, a relatively specific cyclic AMP and a relatively specific cyclic GMP phosphodiesterase were secreted from platelets into the plasma in soluble form. The amounts of the phosphodiesterases secreted were dose- or time-dependent on thrombin (0.1 to 2 units) or A-23187 (5 to 20 muM) within 30 min. The enzyme release by thrombin was completely inhibited by heparin but the release by A-23187 was not. The two phosphodiesterases secreted seemed to correspond to the two enzymes isolated from platelet homogenates in many respects. Rat platelets contained, at least, three cyclic 3':5'-nucleotide phosphodiesterases, namely, two relatively specific cyclic AMP phoshodiesterases and a relatively specific cyclic GMP phosphodiesterase which were clearly separated from each other by Sepharose 6B or DEAE-cellulose column chromatography or sucrose gradient centrifugation. The two platelet cyclic AMP phosphodiesterase (Mr = 180,000 and 280,000) had similar apparent Km values of 0.69 and 0.75 muM with different sedimentation coefficient values of 4.9 S and 7.1 S, respectively. They did not hydrolyze cyclic GMP significantly. A cyclic GMP phosphodiesterase (Mr - 260,000) exhibited abnormal kinetics for cyclic GMP with an apparent Km value of 1.5 muM and normal kinetics for cyclic AMP with a Km of 300 muM. The properties of a platelet cyclic AMP phosphodiesterase (Mr = 180,000) and a platelet cyclic GMP phosphodiesterase were found to agree with those of the two phosphodiesterases released from platelets by thrombin or A-23187. Depletion of extracellular calcium by an addition of citrate, EDTA, or ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) to the blood or platelet suspension resulted in a loss of the activity of the smaller form of platelet cyclic AMP phosphodiesterase (Mr = 180,000) and addition of calcium restored the activity of this cyclic AMP phosphodiesterase. Thus, calcium seemed to be involved in the mechanism of an occurrence of this smaller form of cyclic AMP phosphodiesterase as well as the secretion of this enzyme. Contact of human platelets with thrombin also resulted in the secretion of cyclic nucleotide phosphodiesterase which was dependent on the concentration of calcium. No species difference was observed in this respect.", "contents": "Platelet cyclic 3':5'-nucleotide phosphodiesterase released by thrombin and calcium ionophore. Contact of rat platelets with thrombin or the divalent cation ionophore A-23187, in the presence of extracellular calcium, resulted in the secretion of adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP) phosphodiesterases. Significant association of calcium with platelets occurred during platelet surface contact with thrombin. Thrombin concentration to induce association of calcium virtually agreed with that to release the enzyme. The finding that A-23187 (5 to 20 muM) also provoked a rapid and marked association of extracellular calcium with platelets suggests that calcium mobilization into the intracellular environment may account, at least in part, for this association between platelet and calcium. Two different phosphodiesterases, a relatively specific cyclic AMP and a relatively specific cyclic GMP phosphodiesterase were secreted from platelets into the plasma in soluble form. The amounts of the phosphodiesterases secreted were dose- or time-dependent on thrombin (0.1 to 2 units) or A-23187 (5 to 20 muM) within 30 min. The enzyme release by thrombin was completely inhibited by heparin but the release by A-23187 was not. The two phosphodiesterases secreted seemed to correspond to the two enzymes isolated from platelet homogenates in many respects. Rat platelets contained, at least, three cyclic 3':5'-nucleotide phosphodiesterases, namely, two relatively specific cyclic AMP phoshodiesterases and a relatively specific cyclic GMP phosphodiesterase which were clearly separated from each other by Sepharose 6B or DEAE-cellulose column chromatography or sucrose gradient centrifugation. The two platelet cyclic AMP phosphodiesterase (Mr = 180,000 and 280,000) had similar apparent Km values of 0.69 and 0.75 muM with different sedimentation coefficient values of 4.9 S and 7.1 S, respectively. They did not hydrolyze cyclic GMP significantly. A cyclic GMP phosphodiesterase (Mr - 260,000) exhibited abnormal kinetics for cyclic GMP with an apparent Km value of 1.5 muM and normal kinetics for cyclic AMP with a Km of 300 muM. The properties of a platelet cyclic AMP phosphodiesterase (Mr = 180,000) and a platelet cyclic GMP phosphodiesterase were found to agree with those of the two phosphodiesterases released from platelets by thrombin or A-23187. Depletion of extracellular calcium by an addition of citrate, EDTA, or ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) to the blood or platelet suspension resulted in a loss of the activity of the smaller form of platelet cyclic AMP phosphodiesterase (Mr = 180,000) and addition of calcium restored the activity of this cyclic AMP phosphodiesterase. Thus, calcium seemed to be involved in the mechanism of an occurrence of this smaller form of cyclic AMP phosphodiesterase as well as the secretion of this enzyme. Contact of human platelets with thrombin also resulted in the secretion of cyclic nucleotide phosphodiesterase which was dependent on the concentration of calcium. No species difference was observed in this respect."}
{"id": "PMID:187591", "title": "Mechanism of self-phosphorylation of adenosine 3':5'-monophosphate-dependent protein kinase from bovine cardiac muscle.", "content": "The adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase purified from bovine cardiac muscle catalyzes the transfer of up to 2 mol of 32P from [lambda-32P]ATP to seryl residues in its cyclic nucleotide-binding protein component (Erlichman, J., Rosenfeld, R., and Rosen, O. M. (1974) J. Biol. Chem. 249, 5000-5003). We now present three lines of evidence to support our conclusions that the undissociated holoenzyme does not catalyze the phosphorylation of exogenous substrates but can undergo self-phosphorylation by an intramolecular reaction: (a) addition of either cAMP-binding protein or the protein kinase inhibitor (Walsh, D. A., Ashby C. D., Gonzales, C., Calkins, D., Fischer, E. H., and Krebs, D. G. (1971) J. Biol. Chem. 241, 1977-1985) does not inhibit self-phosphorylation as it does phosphorylation of exogenous substrates in the presence or absence of cAMP; (b) addition of catalytic subunit to an excess of cyclic nucleotide-binding protein results in phosphorylation equivalent to the amount of holoenzyme so generated; (c) the rate of self-phosphorylation is not affected by dilution of the holoenzyme.", "contents": "Mechanism of self-phosphorylation of adenosine 3':5'-monophosphate-dependent protein kinase from bovine cardiac muscle. The adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase purified from bovine cardiac muscle catalyzes the transfer of up to 2 mol of 32P from [lambda-32P]ATP to seryl residues in its cyclic nucleotide-binding protein component (Erlichman, J., Rosenfeld, R., and Rosen, O. M. (1974) J. Biol. Chem. 249, 5000-5003). We now present three lines of evidence to support our conclusions that the undissociated holoenzyme does not catalyze the phosphorylation of exogenous substrates but can undergo self-phosphorylation by an intramolecular reaction: (a) addition of either cAMP-binding protein or the protein kinase inhibitor (Walsh, D. A., Ashby C. D., Gonzales, C., Calkins, D., Fischer, E. H., and Krebs, D. G. (1971) J. Biol. Chem. 241, 1977-1985) does not inhibit self-phosphorylation as it does phosphorylation of exogenous substrates in the presence or absence of cAMP; (b) addition of catalytic subunit to an excess of cyclic nucleotide-binding protein results in phosphorylation equivalent to the amount of holoenzyme so generated; (c) the rate of self-phosphorylation is not affected by dilution of the holoenzyme."}
{"id": "PMID:187592", "title": "Effect of Ca2+ binding on troponin C. Changes in spin label mobility, extrinsic fluorescence, and sulfhydryl reactivity.", "content": "The Ca2+ binding component (TnC) of troponin has been selectively labeled with either a spin label, N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl) iodoacetamide, or with a fluorescent probe, S-mercuric-N-dansyl cysteine, presumably at its single cysteine residue (Cys-98) in order to probe the interactions of TnC with divalent metals and with other subunits of troponin. The modified protein has the same Ca2+ binding properties as native TnC (Potter, J. D., and Gergely, J. (1975) J. Biol. Chem. 250, 4628), viz. two Ca2+ binding sites at which Mg2+ appears to compete (Ca2+-Mg2+ sites, KCa = 2 X 10(7) M-1) and two sites at which Mg2+ does not compete (Ca2+-specific sites, KCa = 2 X 10(5) M-1). Either Ca2+ or Mg2+ alters the ESR spectrum of spin-labeled TnC in a manner that indicates a decrease in the mobility of the label, Ca2+ having a slightly greater effect. In systems containing both Ca2+ and Mg2+ the mobility of the spin label is identical with that in systems containing Ca2+ alone. The binding constants for Ca2+ and Mg2+ deduced from ESR spectral changes are 10(7) and 10(3) M-1, respectively, and the apparent affinity for Ca2+ decreases by about an order of magnitude on adding 2 mM Mg2+. Thus, the ESR spectral change is associated with binding of Ca2+ to one or both of the Ca2+-Mg2+ sites. Addition of Ca2+ to the binary complexes of spin-labeled TnC with either troponin T (TnT) or troponin I (TnI) produces greater reduction in the mobility of the spin label than in the case of spin-labeled TnC alone, and in the case of the complex with TnI the affinity for Ca2+ is increased by an order of magnitude. The fluorescence of dansyl (5-dimethylaminonaphthalene-1-sulfonyl)-labeled TnC is enhanced by Ca2+ binding to both high and low affinity sites with apparent binding constants of 2.6 X 10(7) M-1 and 2.9 X 10(5) M-1, respectively, calculated from the transition midpoints. The presence of 2 mM Mg2+, which produces no effect on dansyl fluorescence itself, in contrast to its effect on the spin label, shifts the high affinity constant to 2 X 10(6) M-1. Spectral changes produced by Ca2+ binding to the TnC-TnI complex furnish evidence that the affinity of TnC for Ca2+ is increased in the complex. The reactivity of Cys-98 to the labels and to 5,5'-dithiobis(2-nitrobenzoic acid) (Nbs2) is decreased by Ca2+ or Mg2+ both with native TnC and in 6 M urea. The reaction rate between Cys-98 and Nbs2 decreases to one-half the maximal value at a Ca2+ concentration that suggests binding to the Ca2+-Mg2+ sites. Formation of a binary complex between TnI and TnC reduces the rate of reaction, and there is a further reduction by Ca2+. The effect of Ca2+ takes place at concentrations that are 1 order of magnitude lower than in the case of TnC alone. These results suggest that the Ca2+ binding site adjacent to Cys-98 is one of the Ca2+-Mg2+ binding sites.", "contents": "Effect of Ca2+ binding on troponin C. Changes in spin label mobility, extrinsic fluorescence, and sulfhydryl reactivity. The Ca2+ binding component (TnC) of troponin has been selectively labeled with either a spin label, N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl) iodoacetamide, or with a fluorescent probe, S-mercuric-N-dansyl cysteine, presumably at its single cysteine residue (Cys-98) in order to probe the interactions of TnC with divalent metals and with other subunits of troponin. The modified protein has the same Ca2+ binding properties as native TnC (Potter, J. D., and Gergely, J. (1975) J. Biol. Chem. 250, 4628), viz. two Ca2+ binding sites at which Mg2+ appears to compete (Ca2+-Mg2+ sites, KCa = 2 X 10(7) M-1) and two sites at which Mg2+ does not compete (Ca2+-specific sites, KCa = 2 X 10(5) M-1). Either Ca2+ or Mg2+ alters the ESR spectrum of spin-labeled TnC in a manner that indicates a decrease in the mobility of the label, Ca2+ having a slightly greater effect. In systems containing both Ca2+ and Mg2+ the mobility of the spin label is identical with that in systems containing Ca2+ alone. The binding constants for Ca2+ and Mg2+ deduced from ESR spectral changes are 10(7) and 10(3) M-1, respectively, and the apparent affinity for Ca2+ decreases by about an order of magnitude on adding 2 mM Mg2+. Thus, the ESR spectral change is associated with binding of Ca2+ to one or both of the Ca2+-Mg2+ sites. Addition of Ca2+ to the binary complexes of spin-labeled TnC with either troponin T (TnT) or troponin I (TnI) produces greater reduction in the mobility of the spin label than in the case of spin-labeled TnC alone, and in the case of the complex with TnI the affinity for Ca2+ is increased by an order of magnitude. The fluorescence of dansyl (5-dimethylaminonaphthalene-1-sulfonyl)-labeled TnC is enhanced by Ca2+ binding to both high and low affinity sites with apparent binding constants of 2.6 X 10(7) M-1 and 2.9 X 10(5) M-1, respectively, calculated from the transition midpoints. The presence of 2 mM Mg2+, which produces no effect on dansyl fluorescence itself, in contrast to its effect on the spin label, shifts the high affinity constant to 2 X 10(6) M-1. Spectral changes produced by Ca2+ binding to the TnC-TnI complex furnish evidence that the affinity of TnC for Ca2+ is increased in the complex. The reactivity of Cys-98 to the labels and to 5,5'-dithiobis(2-nitrobenzoic acid) (Nbs2) is decreased by Ca2+ or Mg2+ both with native TnC and in 6 M urea. The reaction rate between Cys-98 and Nbs2 decreases to one-half the maximal value at a Ca2+ concentration that suggests binding to the Ca2+-Mg2+ sites. Formation of a binary complex between TnI and TnC reduces the rate of reaction, and there is a further reduction by Ca2+. The effect of Ca2+ takes place at concentrations that are 1 order of magnitude lower than in the case of TnC alone. These results suggest that the Ca2+ binding site adjacent to Cys-98 is one of the Ca2+-Mg2+ binding sites."}
{"id": "PMID:187593", "title": "Agonist-specific refractoriness induced by isoproterenol. Studies with mutant cells.", "content": "The beta-adrenergic catecholamine isoproterenol produces a large, rapid, but often a transient, elevation in cellular content of cyclic AMP. We have used the S49 mouse lymphoma cell line, in which genetic variants with specific defects in the pathway of cyclic AMP generation and function have been isolated, to study the increase and subsequent decrease in cyclic AMP levels (termed refractoriness) following incubation of cells with isoproterenol. In wild type S49 cells, isoproterenol produces a peak response in the cellular content of cyclic AMP within 30 min, but the cyclic AMP level falls rapidly thereafter, approaching basal levels by 6 h. Neither inactivation of the drug nor secretion of a nonspecific inhibitor of adenylate cyclase appears to account for the refractoriness. Because isoproterenol refractory cells can still be stimulated by cholera toxin, refractoriness to isoproterenol does not represent a generalized decrease in cellular cyclic AMP response. Particulate preparations from refractory cells have a selective loss of isoproterenol-responsive adenylate cyclase activity, but their activation constants and stereoselectivity for (-)- and (+)-isoproterenol are unaltered. In addition, refractory cells have decreased specific binding of the beta-adrenergic antagonist [125I]iodohydroxybenzylpindolol. This decrease appears to represent a reduction in the number, but not the affinity, of beta-adrenergic receptor sites. Similar studies in an S49 clone that lacks the enzyme cyclic AMP-dependent protein kinase yield essentially identical findings. Because kinase-deficient cells do not induce the cyclic AMP-degrading enzyme phosphodiesterase after the cellular content of cyclic AMP is increased, induced of phosphodiesterase cannot account for refractoriness to isoproterenol. Cyclic AMP-dependent protein kinase does not appear to be required for either the decrease in beta-adrenergic receptors and isoproterenol-responsive adenylate cyclase, nor does it appear to be required for the development of refractoriness to isoproterenol. In contrast, an S49 clone lacking hormone-responsive adenylate cyclase activity but retaining beta-adrenergic receptors does not appear to lose receptors after being incubated with isoproterenol, either alone or together with dibutyryl cyclic AMP. Therefore, in this clone, receptor occupancy alone or in combination with elevated cyclic AMP levels is insufficient to cause refractoriness. Refractoriness thus appears to require intact adenylate cyclase. This suggests that adenylate cyclase may exert regulatory controls on beta-adrenergic receptors in addition to generation of cyclic AMP.", "contents": "Agonist-specific refractoriness induced by isoproterenol. Studies with mutant cells. The beta-adrenergic catecholamine isoproterenol produces a large, rapid, but often a transient, elevation in cellular content of cyclic AMP. We have used the S49 mouse lymphoma cell line, in which genetic variants with specific defects in the pathway of cyclic AMP generation and function have been isolated, to study the increase and subsequent decrease in cyclic AMP levels (termed refractoriness) following incubation of cells with isoproterenol. In wild type S49 cells, isoproterenol produces a peak response in the cellular content of cyclic AMP within 30 min, but the cyclic AMP level falls rapidly thereafter, approaching basal levels by 6 h. Neither inactivation of the drug nor secretion of a nonspecific inhibitor of adenylate cyclase appears to account for the refractoriness. Because isoproterenol refractory cells can still be stimulated by cholera toxin, refractoriness to isoproterenol does not represent a generalized decrease in cellular cyclic AMP response. Particulate preparations from refractory cells have a selective loss of isoproterenol-responsive adenylate cyclase activity, but their activation constants and stereoselectivity for (-)- and (+)-isoproterenol are unaltered. In addition, refractory cells have decreased specific binding of the beta-adrenergic antagonist [125I]iodohydroxybenzylpindolol. This decrease appears to represent a reduction in the number, but not the affinity, of beta-adrenergic receptor sites. Similar studies in an S49 clone that lacks the enzyme cyclic AMP-dependent protein kinase yield essentially identical findings. Because kinase-deficient cells do not induce the cyclic AMP-degrading enzyme phosphodiesterase after the cellular content of cyclic AMP is increased, induced of phosphodiesterase cannot account for refractoriness to isoproterenol. Cyclic AMP-dependent protein kinase does not appear to be required for either the decrease in beta-adrenergic receptors and isoproterenol-responsive adenylate cyclase, nor does it appear to be required for the development of refractoriness to isoproterenol. In contrast, an S49 clone lacking hormone-responsive adenylate cyclase activity but retaining beta-adrenergic receptors does not appear to lose receptors after being incubated with isoproterenol, either alone or together with dibutyryl cyclic AMP. Therefore, in this clone, receptor occupancy alone or in combination with elevated cyclic AMP levels is insufficient to cause refractoriness. Refractoriness thus appears to require intact adenylate cyclase. This suggests that adenylate cyclase may exert regulatory controls on beta-adrenergic receptors in addition to generation of cyclic AMP."}
{"id": "PMID:187594", "title": "Spectral evidence for a flavin adduct in a monoalkylated derivative of pig heart lipoamide dehydrogenase.", "content": "A derivative of the flavoprotein pig heart lipoamide dehydrogenase has been described recently (Thorpe, C., and Williams, C.H. (1976) J. Biol. Chem. 251, 3553-3557), in which 1 of the 2 cysteine residues generated on reduction of the intrachain active center disulfide bridge is selectively alkylated with iodoacetamide. This monolabeled enzyme exhibits a spectrum of oxidized bound flavin. The addition of 1 mM NAD+ to this derivative at pH 8.3 causes a decrease in absorbance of approximately 50% at 448 nm, with a concomitant increase at 380 nm. These spectral changes are complete within 3 ms and are reversible. NAD+ titrations generate isosbestic points at 408, 374, and 327 nm; allowing values for the apparent dissociation constant for NAD+ and the extent of bleaching at infinite ligand to be obtained from double reciprocal plots. Between pH 6.1 and 8.8, the apparent KD decreases from 320 to 35 muM, whereas the extrapolated delta epsilon 448 values remain approximately constant at 1/2 epsilon 448. Direct measurement of NAD+ binding by gel filtration at pH 8.8 indicates that the spectral changes are associated with a stoichiometry of 1.2 mol of NAD+ bound/2 mol of FAD. The modified protein is a dimer containing 1 FAD and 1 alkylated cysteine residue/subunit; the native enzyme is also dimeric. The visible spectrum of the species absorbing at 380 nm, approximated by correction for the residual oxidized FAD, shows a single maximum at 384 nm, epsilon 384 = 8.7 mM-1cm-1. Comparison of this spectrum with that of model compounds of known structure suggests that it may represent a reversible covalent flavin adduct induced on binding NAD+.", "contents": "Spectral evidence for a flavin adduct in a monoalkylated derivative of pig heart lipoamide dehydrogenase. A derivative of the flavoprotein pig heart lipoamide dehydrogenase has been described recently (Thorpe, C., and Williams, C.H. (1976) J. Biol. Chem. 251, 3553-3557), in which 1 of the 2 cysteine residues generated on reduction of the intrachain active center disulfide bridge is selectively alkylated with iodoacetamide. This monolabeled enzyme exhibits a spectrum of oxidized bound flavin. The addition of 1 mM NAD+ to this derivative at pH 8.3 causes a decrease in absorbance of approximately 50% at 448 nm, with a concomitant increase at 380 nm. These spectral changes are complete within 3 ms and are reversible. NAD+ titrations generate isosbestic points at 408, 374, and 327 nm; allowing values for the apparent dissociation constant for NAD+ and the extent of bleaching at infinite ligand to be obtained from double reciprocal plots. Between pH 6.1 and 8.8, the apparent KD decreases from 320 to 35 muM, whereas the extrapolated delta epsilon 448 values remain approximately constant at 1/2 epsilon 448. Direct measurement of NAD+ binding by gel filtration at pH 8.8 indicates that the spectral changes are associated with a stoichiometry of 1.2 mol of NAD+ bound/2 mol of FAD. The modified protein is a dimer containing 1 FAD and 1 alkylated cysteine residue/subunit; the native enzyme is also dimeric. The visible spectrum of the species absorbing at 380 nm, approximated by correction for the residual oxidized FAD, shows a single maximum at 384 nm, epsilon 384 = 8.7 mM-1cm-1. Comparison of this spectrum with that of model compounds of known structure suggests that it may represent a reversible covalent flavin adduct induced on binding NAD+."}
{"id": "PMID:187595", "title": "Gonadotropin-induced loss of hormone receptors and desensitization of adenylate cyclase in the ovary.", "content": "Gonadotropin receptor sites and adenylate cyclase activity were analyzed in luteinized rat ovaries following injection of human chorionic gonadotropin (hCG). Gonadotropin binding capacity and hormonal stimulation of adenylate cyclase declined rapidly to a minimum at 6 to 12 h, remained depressed for 4 days, and returned to the control level between 5 and 7 days. Total adenylate cyclase activity measured in the presence of fluoride fell by 50% within a few hours but returned to normal by 24 h. A close correlation was observed between the number of gonadotropin receptors and the ability of adenylate cyclase to be stimulated by hormone. Assay of tissue-bound hormone showed that the initial loss of hormone sensitivity and binding capacity was associated with occupancy of luteinizing hormone receptor sites, but that the prolonged changes in these activities were not attributable to receptor occupancy. These studies have demonstrated that induction of a refractory or desensitized state in ovarian adenylate cyclase by gonadotropin results from the loss of specific hormone receptor sites.", "contents": "Gonadotropin-induced loss of hormone receptors and desensitization of adenylate cyclase in the ovary. Gonadotropin receptor sites and adenylate cyclase activity were analyzed in luteinized rat ovaries following injection of human chorionic gonadotropin (hCG). Gonadotropin binding capacity and hormonal stimulation of adenylate cyclase declined rapidly to a minimum at 6 to 12 h, remained depressed for 4 days, and returned to the control level between 5 and 7 days. Total adenylate cyclase activity measured in the presence of fluoride fell by 50% within a few hours but returned to normal by 24 h. A close correlation was observed between the number of gonadotropin receptors and the ability of adenylate cyclase to be stimulated by hormone. Assay of tissue-bound hormone showed that the initial loss of hormone sensitivity and binding capacity was associated with occupancy of luteinizing hormone receptor sites, but that the prolonged changes in these activities were not attributable to receptor occupancy. These studies have demonstrated that induction of a refractory or desensitized state in ovarian adenylate cyclase by gonadotropin results from the loss of specific hormone receptor sites."}
{"id": "PMID:187596", "title": "Purification and properties of an endonuclease from nuclei of uninfected and polyoma-infected 3T3 cells.", "content": "An endonuclease activity has been purified approximately 800-fold from nuclei of 3T3 cells infected with polyoma virus. The purfied enzyme catalyzes an endonucleoytic cleavage of single- and double-stranded DNA and single-stranded RNA. Evidence that the activity towards these substrates resides in the same protein molecule is provided by the finding that they co-sediment in sucrose gradients and have identical rates of heat inactivation. Studies on the DNase activity shows that the rate of hydrolysis of single-stranded T7 DNA is 100-fold greater than that for double-stranded T7 DNA. Single-stranded DNA is extensively hydrolyzed to low molecular weight acid-insoluble products. With duplex DNA as substrate, only a limited number of single strand breaks are introduced. A limit digest with polyoma DNA (component I) as substrate results in the introduction of four breaks per strand. The phosphdiester bond interruptions can be repaired by polynucleotide ligase. Approximately 80% of the 5' termini present at the point of phosphodiester bond cleavage are purine nucleotides. Additional studies have demonstrated that a similar endonuclease is present in nuclei of uninfected cells and that this enzyme purified 400-fold has catalytic properties identical with those of the endonuclease from infected cells.", "contents": "Purification and properties of an endonuclease from nuclei of uninfected and polyoma-infected 3T3 cells. An endonuclease activity has been purified approximately 800-fold from nuclei of 3T3 cells infected with polyoma virus. The purfied enzyme catalyzes an endonucleoytic cleavage of single- and double-stranded DNA and single-stranded RNA. Evidence that the activity towards these substrates resides in the same protein molecule is provided by the finding that they co-sediment in sucrose gradients and have identical rates of heat inactivation. Studies on the DNase activity shows that the rate of hydrolysis of single-stranded T7 DNA is 100-fold greater than that for double-stranded T7 DNA. Single-stranded DNA is extensively hydrolyzed to low molecular weight acid-insoluble products. With duplex DNA as substrate, only a limited number of single strand breaks are introduced. A limit digest with polyoma DNA (component I) as substrate results in the introduction of four breaks per strand. The phosphdiester bond interruptions can be repaired by polynucleotide ligase. Approximately 80% of the 5' termini present at the point of phosphodiester bond cleavage are purine nucleotides. Additional studies have demonstrated that a similar endonuclease is present in nuclei of uninfected cells and that this enzyme purified 400-fold has catalytic properties identical with those of the endonuclease from infected cells."}
{"id": "PMID:187597", "title": "Hormonal control of [14C]glucose synthesis from [U-14C]dihydroxyacetone and glycerol in isolated rat hepatocytes.", "content": "The hormonal control of [14C]glucose synthesis from [U-14C-A1dihydroxyacetone was studied in hepatocytes from fed and starved rats. In cells from fed rats, glucagon lowered the concentration of substrate giving half-half-maximal rates of incorporation while it had little or no effect on the maximal rate. Inhibitors of gluconeogenesis from pyruvate had no effect on the ability of the hormone to stimulate the synthesis of [14C]glucose from dihydroxyacetone. The concentrations of glucagon and epinephrine giving half-maximal stimulation from dihydroxacetone were 0.3 to 0.4 mM and 0.3 to 0.5 muM, respectively. The meaximal catecholamine stimulation was much less than the maximal stimulation by glucagon and was mediated largely by the alpha receptor. Insulin had no effect on the basal rate of [14C]clucose synthesis but inhibited the effect of submaximal concentration of glucagon or of any concentration of catecholamine. Glucagon had no effect on the uptake of dihydroxyacetone but suppressed its conversion to lactate and pyruvate. This suppression accounted for most of the increase in glucose synthesis. In cells from gasted rats, where lactate production is greatly reduced and the rate of glucose synthesis is elevated, glucagon did not stimulate gluconeogenesis from dihydroxyacetone. Findings with glycerol as substrate were similar to those with dihyroxyacetone. Ethanol also stimulated glucose production from dihydroxyacetone while reducing proportionately the production of lactate. Ethanol  is known to generate reducing equivalents fro clyceraldehyde-3-phosphate dehydrogenase and presumably thereby inhibits carbon flux to lactate at this site. Its effect was additive with that of glucagon. Estimates of the steady state levels of intermediary metabolites and flux rates suggested that glucagon activated conversion of fructose diphosphate to fructose 6-phosphate and suppressed conversion of phosphoenolpyruvate to pyruvate. More direct evidence for an inhibition of pyruvate kinase was the observation that brief exposure of cells to glucagon caused up to 70% inhibition of the enzyme activity in homogenates of these cells. The inhibition was not seen when the enzyme was assayed with 20 muM fructose diphosphate. The effect of glucagon to lower fructose diphosphate levels in intact cells may promote the inhibition of pyruvate kinase. The inhibition of pyruvate kinase may reduce recycling in the pathway of gluconeogenesis from major physiological substrates and probably accounts fromsome but not all the stimulatory effect of glucagon.", "contents": "Hormonal control of [14C]glucose synthesis from [U-14C]dihydroxyacetone and glycerol in isolated rat hepatocytes. The hormonal control of [14C]glucose synthesis from [U-14C-A1dihydroxyacetone was studied in hepatocytes from fed and starved rats. In cells from fed rats, glucagon lowered the concentration of substrate giving half-half-maximal rates of incorporation while it had little or no effect on the maximal rate. Inhibitors of gluconeogenesis from pyruvate had no effect on the ability of the hormone to stimulate the synthesis of [14C]glucose from dihydroxyacetone. The concentrations of glucagon and epinephrine giving half-maximal stimulation from dihydroxacetone were 0.3 to 0.4 mM and 0.3 to 0.5 muM, respectively. The meaximal catecholamine stimulation was much less than the maximal stimulation by glucagon and was mediated largely by the alpha receptor. Insulin had no effect on the basal rate of [14C]clucose synthesis but inhibited the effect of submaximal concentration of glucagon or of any concentration of catecholamine. Glucagon had no effect on the uptake of dihydroxyacetone but suppressed its conversion to lactate and pyruvate. This suppression accounted for most of the increase in glucose synthesis. In cells from gasted rats, where lactate production is greatly reduced and the rate of glucose synthesis is elevated, glucagon did not stimulate gluconeogenesis from dihydroxyacetone. Findings with glycerol as substrate were similar to those with dihyroxyacetone. Ethanol also stimulated glucose production from dihydroxyacetone while reducing proportionately the production of lactate. Ethanol  is known to generate reducing equivalents fro clyceraldehyde-3-phosphate dehydrogenase and presumably thereby inhibits carbon flux to lactate at this site. Its effect was additive with that of glucagon. Estimates of the steady state levels of intermediary metabolites and flux rates suggested that glucagon activated conversion of fructose diphosphate to fructose 6-phosphate and suppressed conversion of phosphoenolpyruvate to pyruvate. More direct evidence for an inhibition of pyruvate kinase was the observation that brief exposure of cells to glucagon caused up to 70% inhibition of the enzyme activity in homogenates of these cells. The inhibition was not seen when the enzyme was assayed with 20 muM fructose diphosphate. The effect of glucagon to lower fructose diphosphate levels in intact cells may promote the inhibition of pyruvate kinase. The inhibition of pyruvate kinase may reduce recycling in the pathway of gluconeogenesis from major physiological substrates and probably accounts fromsome but not all the stimulatory effect of glucagon."}
{"id": "PMID:187598", "title": "Endgoenous protein kinase in outer plasma membrane of cultured 3T3 cells. Nature of the membrane-bound substrate and effect of cell density, serum addition, and oncogenic transformation.", "content": "Endogenous protein kinase activity was detected in the outer plasma membrane of 373 and SV40 transformed 3T3 cells. When intact cells were incubated with [gamma-32P]ATP, there was a transfer of [32P]phosphate into an acid-insoluble product. The reaction was: (a) linear as a function of time (up to 30 min), (b) proportional to the number of cells present and (c) dependent on temperature and Mg2+ concentration. The acid-insoluble product was susceptible to pronase but not RNase or DNase. More specifically, phosphomonoester bonds to serine and threonine were identified. There was less than 3% hydrolysis of the [gamma-32P]ATP during the reaction; moreover, free [32P]phosphate failed to substitute for the ATP. The reaction product was located on the cell surface, as evidenced by the fact that it could be removed by mild trypsin treatment of intact 3T3 cells. Further evidence for the surface location of the kinase was shown by its activity in phosphorlating exogenous substrate, histone, and phosvitin. The level of phosphorylation increased by 2- to 4-fold prior to the start of S phase when quiescent 3T3 cells were stimulated to reinitiate growth by the addition of serum. The SV40 3T3 cells had from 5- to 10-fold more activity per cell than the quiescent 3T3 cells. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and radioautography show at least 25 phosphorylated proteins; the surface label pattern of 3T3 cells differs from that of SV40-transformed 3T3 cells.", "contents": "Endgoenous protein kinase in outer plasma membrane of cultured 3T3 cells. Nature of the membrane-bound substrate and effect of cell density, serum addition, and oncogenic transformation. Endogenous protein kinase activity was detected in the outer plasma membrane of 373 and SV40 transformed 3T3 cells. When intact cells were incubated with [gamma-32P]ATP, there was a transfer of [32P]phosphate into an acid-insoluble product. The reaction was: (a) linear as a function of time (up to 30 min), (b) proportional to the number of cells present and (c) dependent on temperature and Mg2+ concentration. The acid-insoluble product was susceptible to pronase but not RNase or DNase. More specifically, phosphomonoester bonds to serine and threonine were identified. There was less than 3% hydrolysis of the [gamma-32P]ATP during the reaction; moreover, free [32P]phosphate failed to substitute for the ATP. The reaction product was located on the cell surface, as evidenced by the fact that it could be removed by mild trypsin treatment of intact 3T3 cells. Further evidence for the surface location of the kinase was shown by its activity in phosphorlating exogenous substrate, histone, and phosvitin. The level of phosphorylation increased by 2- to 4-fold prior to the start of S phase when quiescent 3T3 cells were stimulated to reinitiate growth by the addition of serum. The SV40 3T3 cells had from 5- to 10-fold more activity per cell than the quiescent 3T3 cells. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and radioautography show at least 25 phosphorylated proteins; the surface label pattern of 3T3 cells differs from that of SV40-transformed 3T3 cells."}
{"id": "PMID:187599", "title": "Electronic state of heme in cytochrome oxidase. I. Magnetic circular dichroism of the isolated enzyme and its derivatives.", "content": "Magnetic circular dichroism (MCD) spectra have been recorded for beef heart cytochrome oxidase and a number of its inhibitor complexes. The resting enzyme exhibits a derivate shape Faraday C term in the Soret region, characteristic of low spin ferric heme, which accounts for 50% of the total oxidase heme a. The remaining heme a (50%) is assigned to the high spin state. MCD temperature studies, comparison with the MCD spectra of heme a-imidazole model compounds, and ligand binding (cyanide, formate) studies are consistent with these spin state assignments in the oxidized enzyme. Furthermore, the ligand binding properties and correlations between optical and MCD parameters indicate that in the resting enzyme the low spin heme a is due solely to cytochrome a3+ and the high spin heme a to cytochrome a33+. The Soret MCD of the reduced protein is interpreted as th sum of two MCD curves: an intense, asymmetric MCD band very similar to that exhibited by deoxymyoglobin which we assign to paramagnetic high spin cytochrome a3(2+) and a weaker, more symmetric MCD contribution, which is attributed to diamagnetic low spin cytochrome a2+. Temperature studies of the Soret MCD intensity support this proposed spin state heterogeneity. Ligand binding (CO, CN-) to the reduced protein eliminates the intense MCD associated with high spin cytochrome a3(2+); however, the band associated with cytochrome a2+ is observed under these conditions as well as in a number of inhibitor complexes (cyanide, formate, sulfide, azide) of the partially reduced protein. The MCD spectra of oxidized, reduced, and inhibitor-complexed cytochrome oxidase show no evidence for heme-heme interaction via spectral parameters. This conclusion is used in conjunction with the fact that ferric, high spin heme exhibits weak MCD intensity to calculate the MCD spectra for the individual cytochromes of the oxidase as well as the spectra for some inhibitor complexes of cytochrome a3. The results are most simply interpreted using the model we have recently proposed to account for the electronic and magnetic properties of cytochrome (Palmer, G., Babcock, F.T., and Vcikery, L.E. (1976) Proc. Natl. Acad. Sci. U. S. A. 73, 2206-2210).", "contents": "Electronic state of heme in cytochrome oxidase. I. Magnetic circular dichroism of the isolated enzyme and its derivatives. Magnetic circular dichroism (MCD) spectra have been recorded for beef heart cytochrome oxidase and a number of its inhibitor complexes. The resting enzyme exhibits a derivate shape Faraday C term in the Soret region, characteristic of low spin ferric heme, which accounts for 50% of the total oxidase heme a. The remaining heme a (50%) is assigned to the high spin state. MCD temperature studies, comparison with the MCD spectra of heme a-imidazole model compounds, and ligand binding (cyanide, formate) studies are consistent with these spin state assignments in the oxidized enzyme. Furthermore, the ligand binding properties and correlations between optical and MCD parameters indicate that in the resting enzyme the low spin heme a is due solely to cytochrome a3+ and the high spin heme a to cytochrome a33+. The Soret MCD of the reduced protein is interpreted as th sum of two MCD curves: an intense, asymmetric MCD band very similar to that exhibited by deoxymyoglobin which we assign to paramagnetic high spin cytochrome a3(2+) and a weaker, more symmetric MCD contribution, which is attributed to diamagnetic low spin cytochrome a2+. Temperature studies of the Soret MCD intensity support this proposed spin state heterogeneity. Ligand binding (CO, CN-) to the reduced protein eliminates the intense MCD associated with high spin cytochrome a3(2+); however, the band associated with cytochrome a2+ is observed under these conditions as well as in a number of inhibitor complexes (cyanide, formate, sulfide, azide) of the partially reduced protein. The MCD spectra of oxidized, reduced, and inhibitor-complexed cytochrome oxidase show no evidence for heme-heme interaction via spectral parameters. This conclusion is used in conjunction with the fact that ferric, high spin heme exhibits weak MCD intensity to calculate the MCD spectra for the individual cytochromes of the oxidase as well as the spectra for some inhibitor complexes of cytochrome a3. The results are most simply interpreted using the model we have recently proposed to account for the electronic and magnetic properties of cytochrome (Palmer, G., Babcock, F.T., and Vcikery, L.E. (1976) Proc. Natl. Acad. Sci. U. S. A. 73, 2206-2210)."}
{"id": "PMID:187600", "title": "Steady state and exchange kinetics of pyruvate, phosphate dikinase from Propionibacterium shermanii.", "content": "Evidence is presented based on requirements for exchange in the partial reactions, initial velocity and exchange kinetics and product inhibition, that the pyruvate, phosphate dikinase reaction of propionibacteria occurs by a nonclassical Tri Uni Uni Ping Pong mechanism. The mechanism involves a pyrophosphoryl enzyme, a phosphoryl enzyme, and the free enzyme, and three functionally distinct and independent substrate sites. On the first site, there is pyrophosphorylation of the enzyme by ATP with subsequent release of AMP. The pyrophosphoryl moiety then reacts at the second site with Pi yielding the product PPi and the phosphoryl from of the enzyme. At the third site pyruvate is phosphorylated yielding P-enolpyruvate and the free enzyme. The three catalytic sites are proposed to be linked by a histidyl residue which functions as a pyrophosphoyrl- and phosphoryl-carrier between the three sites. This proposal is based on the following observations. (A) The patterns of the double reciprocal plots of the initial velocities were all parallel; (b) product inhibition between each pair of substrates and products of the three partial reactions were competitive, i.e. ATP against AMP, Pi against PPi, and pyruvate against P-enolpyruvate; (c) the other product inhibitions, with one exception, were noncompetitive as required by the nonclassical ping-pong mechanism; (d) ATP or P-enolpyruvate was required for the Pi in equilibrium PPi exchange reaction which is in accord with the participation of a pyrosphosphoryl or phosphoryl form of the enzyme in this exchange; (e) the ATP in equilibrium AMP exchange and pyruvate in equilibrium P-enolpyruvate exchange did not require additional substrates. In addition, the inhibition and participation in the exchange reactions of the alpha,beta and beta,gamma-methylene analogues of ATP and of the methylene analogue of inorganic pyrophosphate were investigated and the results were in accord with the proposed mechanism. The combined evidence provides a well documented example of a three site nonclassical Tri Uni Uni Ping Pong mechanism.", "contents": "Steady state and exchange kinetics of pyruvate, phosphate dikinase from Propionibacterium shermanii. Evidence is presented based on requirements for exchange in the partial reactions, initial velocity and exchange kinetics and product inhibition, that the pyruvate, phosphate dikinase reaction of propionibacteria occurs by a nonclassical Tri Uni Uni Ping Pong mechanism. The mechanism involves a pyrophosphoryl enzyme, a phosphoryl enzyme, and the free enzyme, and three functionally distinct and independent substrate sites. On the first site, there is pyrophosphorylation of the enzyme by ATP with subsequent release of AMP. The pyrophosphoryl moiety then reacts at the second site with Pi yielding the product PPi and the phosphoryl from of the enzyme. At the third site pyruvate is phosphorylated yielding P-enolpyruvate and the free enzyme. The three catalytic sites are proposed to be linked by a histidyl residue which functions as a pyrophosphoyrl- and phosphoryl-carrier between the three sites. This proposal is based on the following observations. (A) The patterns of the double reciprocal plots of the initial velocities were all parallel; (b) product inhibition between each pair of substrates and products of the three partial reactions were competitive, i.e. ATP against AMP, Pi against PPi, and pyruvate against P-enolpyruvate; (c) the other product inhibitions, with one exception, were noncompetitive as required by the nonclassical ping-pong mechanism; (d) ATP or P-enolpyruvate was required for the Pi in equilibrium PPi exchange reaction which is in accord with the participation of a pyrosphosphoryl or phosphoryl form of the enzyme in this exchange; (e) the ATP in equilibrium AMP exchange and pyruvate in equilibrium P-enolpyruvate exchange did not require additional substrates. In addition, the inhibition and participation in the exchange reactions of the alpha,beta and beta,gamma-methylene analogues of ATP and of the methylene analogue of inorganic pyrophosphate were investigated and the results were in accord with the proposed mechanism. The combined evidence provides a well documented example of a three site nonclassical Tri Uni Uni Ping Pong mechanism."}
{"id": "PMID:187601", "title": "Properties of electrophoretically homogeneous phenobarbital-inducible and beta-naphthoflavone-inducible forms of liver microsomal cytochrome P-450.", "content": "Procedures are described for the isolation of two forms of rabbit liver microsomal liver microsomal cytochrome P-450 (P-450LM) in homogeneous state. They are designated by their relative electrophoretic mobilities on polyacrylamide gel in the presence of sodium dodecyl sulfate as P-450LM2 and P-450LM4. P-450LM2, which was isolated from phenobarbital-induced animals, has a subunit molecular weight of 48,700. The best preparations contain 20 nmol of the cytochrome per mg of protein and 1 molecule of heme per polypeptide chain. P-450LM4, which is induced by beta-naphthoflavone but is also present in phenobarbital-induced and untreated animals, was isolated from all three sources and found to have a subunit molecular weight of 55,300. The best preparations contain 17nmol of the cytochrome per mg of protein and 1 molecule of heme per polypeptide chain. Some of the purified preparations of the cytochromes, although electrophoretically homogeneous, contain apoenzyme due to heme loss during purification. The purified proteins contain no detectable NADPH-cytochrome P-450 reductase, cytochrome b5, or NADH-cytochrome b5 reductase, and only low levels of phospholipid (about 1 molecule per subunit). Amino acid analysis indicated that P-450LM2 and P-450LM4 are similar in composition, but the latter protein has about 60 additional residues. The COOH-terminal amino acid of P-450LM2 is arginine, as shown by carboxypeptidase treatment, whereas that of P-450LM4 is lysine. NH2-terminal amino acid residues could not be detected. Carbohydrate analysis indicated that both cytochromes contain 1 residue of glucosamine and 2 of mannose per polypeptide subunit. The optical spectra of the oxidized and reduced cytochromes and carbon monoxide complexes were determined. Oxidized P-450LM2 has maxima at 568, 535, and 418 nm characteristic of a low spin hemeprotein, and P450LM4 from beta-naphthoflavone-induced, phenobarbital-induced, or control microsomes has maxima at 645 and 394 nm, characteristic of the high spin state. The spectrum of -450lm4 becomes similar to that of P-450LM2 at high protein concentrations or upon the addition of detergent (Renex), whereas the spectrum of P-450LM2 is unaffected by the protein concentration or the presence of detergent. Electron paramagnetic resonance spectrometry of the purified cytochromes indicated that oxidized -450lm2 is in the low spin state, whereas P-450LM4 is largely, but not entirely, in the high spin state.", "contents": "Properties of electrophoretically homogeneous phenobarbital-inducible and beta-naphthoflavone-inducible forms of liver microsomal cytochrome P-450. Procedures are described for the isolation of two forms of rabbit liver microsomal liver microsomal cytochrome P-450 (P-450LM) in homogeneous state. They are designated by their relative electrophoretic mobilities on polyacrylamide gel in the presence of sodium dodecyl sulfate as P-450LM2 and P-450LM4. P-450LM2, which was isolated from phenobarbital-induced animals, has a subunit molecular weight of 48,700. The best preparations contain 20 nmol of the cytochrome per mg of protein and 1 molecule of heme per polypeptide chain. P-450LM4, which is induced by beta-naphthoflavone but is also present in phenobarbital-induced and untreated animals, was isolated from all three sources and found to have a subunit molecular weight of 55,300. The best preparations contain 17nmol of the cytochrome per mg of protein and 1 molecule of heme per polypeptide chain. Some of the purified preparations of the cytochromes, although electrophoretically homogeneous, contain apoenzyme due to heme loss during purification. The purified proteins contain no detectable NADPH-cytochrome P-450 reductase, cytochrome b5, or NADH-cytochrome b5 reductase, and only low levels of phospholipid (about 1 molecule per subunit). Amino acid analysis indicated that P-450LM2 and P-450LM4 are similar in composition, but the latter protein has about 60 additional residues. The COOH-terminal amino acid of P-450LM2 is arginine, as shown by carboxypeptidase treatment, whereas that of P-450LM4 is lysine. NH2-terminal amino acid residues could not be detected. Carbohydrate analysis indicated that both cytochromes contain 1 residue of glucosamine and 2 of mannose per polypeptide subunit. The optical spectra of the oxidized and reduced cytochromes and carbon monoxide complexes were determined. Oxidized P-450LM2 has maxima at 568, 535, and 418 nm characteristic of a low spin hemeprotein, and P450LM4 from beta-naphthoflavone-induced, phenobarbital-induced, or control microsomes has maxima at 645 and 394 nm, characteristic of the high spin state. The spectrum of -450lm4 becomes similar to that of P-450LM2 at high protein concentrations or upon the addition of detergent (Renex), whereas the spectrum of P-450LM2 is unaffected by the protein concentration or the presence of detergent. Electron paramagnetic resonance spectrometry of the purified cytochromes indicated that oxidized -450lm2 is in the low spin state, whereas P-450LM4 is largely, but not entirely, in the high spin state."}
{"id": "PMID:187602", "title": "Solubilization of adenylate cyclase from normal and Rous sarcoma-transformed chicken embryo fibroblasts.", "content": "Adenylate cyclase activities in membranes prepared from Rous sarcoma-transformed chicken embryo fibroblasts are 2 to 4 times lower than in membranes prepared from normal chicken embryo fibroblasts. Adenylate cyclase activities were solubilized from normal and transformed membranes with five different nonionic detergents. In all cases, the specific activities of the enzyme solubilized from normal and transformed preparations were essentially identical. These data suggest that the microenvironment of adenylate cyclase in transformed membranes may be wholly or partially responsible for the decreased activities of this enzyme.", "contents": "Solubilization of adenylate cyclase from normal and Rous sarcoma-transformed chicken embryo fibroblasts. Adenylate cyclase activities in membranes prepared from Rous sarcoma-transformed chicken embryo fibroblasts are 2 to 4 times lower than in membranes prepared from normal chicken embryo fibroblasts. Adenylate cyclase activities were solubilized from normal and transformed membranes with five different nonionic detergents. In all cases, the specific activities of the enzyme solubilized from normal and transformed preparations were essentially identical. These data suggest that the microenvironment of adenylate cyclase in transformed membranes may be wholly or partially responsible for the decreased activities of this enzyme."}
{"id": "PMID:187603", "title": "Stopped flow kinetics of pyrene transfer between human high density lipoproteins.", "content": "The transfer of pyrene between high density lipoproteins was studied as a model of lipid exchange. When high density lipoprotein containing pyrene was mixed with unlabeled lipoprotein, pyrene excimer fluorescence decreased with a half-time of approximately 3 ms. The rate of pyrene transfer was invariant over a 100-fold range of unlabeled lipoprotein concentrations. Since a decrease in excimer fluorescence indicates a decrease in the microscopic concentrations of pyrene, the observed fluorescence change relfects pyrene transfer to unlabeled lipoproteins, and, therefore, dilution of the pyrene molecules. When high density lipoprotein labeled with pyrene was rapidly diluted 1:14 into buffer, a small decrease in excimer fluorescence was observed.  The half-time of this fluorescence change was also about 3 ms and represents the half-time for the dissociation of pyrene from high density lipoprotein into water. The latter observation, coupled with the invariant exchange rate with lipoprotein concentration suggests strongly that the limiting step in the transfer of pyrene between high density lipoproteins is the dissociation of pyrene into solvent. Finally, regardless of mechanism, the exchange of pyrene, and presumably other hydrophobic aromatic compounds, among serum high density lipoproteins is extremely fast. This result indicates that these types of compounds can be rapidly assimilated and transported through the body by plasma lipoproteins.", "contents": "Stopped flow kinetics of pyrene transfer between human high density lipoproteins. The transfer of pyrene between high density lipoproteins was studied as a model of lipid exchange. When high density lipoprotein containing pyrene was mixed with unlabeled lipoprotein, pyrene excimer fluorescence decreased with a half-time of approximately 3 ms. The rate of pyrene transfer was invariant over a 100-fold range of unlabeled lipoprotein concentrations. Since a decrease in excimer fluorescence indicates a decrease in the microscopic concentrations of pyrene, the observed fluorescence change relfects pyrene transfer to unlabeled lipoproteins, and, therefore, dilution of the pyrene molecules. When high density lipoprotein labeled with pyrene was rapidly diluted 1:14 into buffer, a small decrease in excimer fluorescence was observed.  The half-time of this fluorescence change was also about 3 ms and represents the half-time for the dissociation of pyrene from high density lipoprotein into water. The latter observation, coupled with the invariant exchange rate with lipoprotein concentration suggests strongly that the limiting step in the transfer of pyrene between high density lipoproteins is the dissociation of pyrene into solvent. Finally, regardless of mechanism, the exchange of pyrene, and presumably other hydrophobic aromatic compounds, among serum high density lipoproteins is extremely fast. This result indicates that these types of compounds can be rapidly assimilated and transported through the body by plasma lipoproteins."}
{"id": "PMID:187604", "title": "Ultrastructural and biochemical evidence for a steroid-containing secretory organelle in the perfused cat adrenal gland.", "content": "A correlative study of the ultrastructural and biochemical effects of ACTH on fasciculata cells was carried out on the isolated cat adrenal gland perfused in situ with Locke's solution. The outstanding morphologic feature of cortical cells exposed to microunit ACTH concentrations for 40 min was the abundance of electron-dense granules (0.2-0.4 mum). These organelles were observed in small groups in close proximity to the Golgi region and to the cell membrane. Morphometric and biochemical analysis of control and ACTH-treated glands demonstrated that ACTH stimulation was associated with a fourfold increase in the number of these granules and a comparable increase in the corticosteroid content of the gland. By contrast, ACTH failed to augment cortical lysosomal enzyme activity. These findings, which link steroid release to the appearance of intracellular granules, extend further the parallels between the mechanism of release of newly synthesized steroid and the release of preformed hormones stored in secretory organelles. These results also lend support to the concept that a process related to exocytosis may be the underlying mechanism for extruding steroid from the cortical cell.", "contents": "Ultrastructural and biochemical evidence for a steroid-containing secretory organelle in the perfused cat adrenal gland. A correlative study of the ultrastructural and biochemical effects of ACTH on fasciculata cells was carried out on the isolated cat adrenal gland perfused in situ with Locke's solution. The outstanding morphologic feature of cortical cells exposed to microunit ACTH concentrations for 40 min was the abundance of electron-dense granules (0.2-0.4 mum). These organelles were observed in small groups in close proximity to the Golgi region and to the cell membrane. Morphometric and biochemical analysis of control and ACTH-treated glands demonstrated that ACTH stimulation was associated with a fourfold increase in the number of these granules and a comparable increase in the corticosteroid content of the gland. By contrast, ACTH failed to augment cortical lysosomal enzyme activity. These findings, which link steroid release to the appearance of intracellular granules, extend further the parallels between the mechanism of release of newly synthesized steroid and the release of preformed hormones stored in secretory organelles. These results also lend support to the concept that a process related to exocytosis may be the underlying mechanism for extruding steroid from the cortical cell."}
{"id": "PMID:187605", "title": "Intranuclear membranous inclusions in oocytes of a viviparous teleost (Xiphophorus helleri).", "content": "Intranuclear inclusions were observed in oocytes of Xiphophorus helleri during prophase I. In osmium-fixed leptotene nuclei, the inclusions were made up of groups of membrane-limited vesicles or tubules with pale contents, situated near the inner nuclear membrane with which some of them exhibited apparent continuities. In zygotene nuclei, larger vesicles also appeared bounded by two or three membranes and containing tubules apparently invaginated from their walls. In pachytene-dictyate nuclei most vesicular bodies had a wall formed by stratified membranes, or were entirely made up of membranous whorls. In glutaraldehyde-osmium fixed material some of these myeline-like bodies showed a peculiar arrangement, consisting of concentric bands each containing thick inner dense lamellae 2-0-3-0 nm thick and a 5-0 nm outer lamella. It is suggested that these inclusion bodies arise from the inner nuclear membrane of oocytes when cells start to grow intensely during prophase I. The bodies seem to become more complex at late prophase, probably by association of individual vesicles and the occurrence of multiple membrane invaginations, which may be related to active metabolic phenomena taking place at this stage in oocytes.", "contents": "Intranuclear membranous inclusions in oocytes of a viviparous teleost (Xiphophorus helleri). Intranuclear inclusions were observed in oocytes of Xiphophorus helleri during prophase I. In osmium-fixed leptotene nuclei, the inclusions were made up of groups of membrane-limited vesicles or tubules with pale contents, situated near the inner nuclear membrane with which some of them exhibited apparent continuities. In zygotene nuclei, larger vesicles also appeared bounded by two or three membranes and containing tubules apparently invaginated from their walls. In pachytene-dictyate nuclei most vesicular bodies had a wall formed by stratified membranes, or were entirely made up of membranous whorls. In glutaraldehyde-osmium fixed material some of these myeline-like bodies showed a peculiar arrangement, consisting of concentric bands each containing thick inner dense lamellae 2-0-3-0 nm thick and a 5-0 nm outer lamella. It is suggested that these inclusion bodies arise from the inner nuclear membrane of oocytes when cells start to grow intensely during prophase I. The bodies seem to become more complex at late prophase, probably by association of individual vesicles and the occurrence of multiple membrane invaginations, which may be related to active metabolic phenomena taking place at this stage in oocytes."}
{"id": "PMID:187607", "title": "Comparison of batch and chromatographic assays of cyclic nucleiotide phosphodiesterases.", "content": "An improved method for the assay of cyclic nucleotide phosphodiesterases (CNPases) is described in which residual 3H-cAMP or 3H-cGMP is separated from products by chromatography on thin layers of PEI-cellulose. Comparison of CNPase activity in crude or purified kidney enzyme assayed by the PEI-cellulose method with a batch anion-exchange resin method showed serious underestimation of activity by the latter method. The batch method underestimated CNPase activity by 34-82%. The error was due to substantial binding of nucleosides (adenosine and guanosine) to the resin, which is assumed not to occur by those using this method.", "contents": "Comparison of batch and chromatographic assays of cyclic nucleiotide phosphodiesterases. An improved method for the assay of cyclic nucleotide phosphodiesterases (CNPases) is described in which residual 3H-cAMP or 3H-cGMP is separated from products by chromatography on thin layers of PEI-cellulose. Comparison of CNPase activity in crude or purified kidney enzyme assayed by the PEI-cellulose method with a batch anion-exchange resin method showed serious underestimation of activity by the latter method. The batch method underestimated CNPase activity by 34-82%. The error was due to substantial binding of nucleosides (adenosine and guanosine) to the resin, which is assumed not to occur by those using this method."}
{"id": "PMID:187608", "title": "Preparative high-performance liquid chromatography applied to peptide synthesis.", "content": "A variety of protected synthetic peptides were purified by high-performance liquid chromatography on pre-packed silica gel columns. The compounds varied in protecting groups, amino acid composition and molecular weight. Flow-rates of two to four column volumes per hour were employed, with resultant back pressure of less than 150 p.s.i. A typical column load of 0.2-5 g was purified in 2-5 h.", "contents": "Preparative high-performance liquid chromatography applied to peptide synthesis. A variety of protected synthetic peptides were purified by high-performance liquid chromatography on pre-packed silica gel columns. The compounds varied in protecting groups, amino acid composition and molecular weight. Flow-rates of two to four column volumes per hour were employed, with resultant back pressure of less than 150 p.s.i. A typical column load of 0.2-5 g was purified in 2-5 h."}
{"id": "PMID:187609", "title": "Liquid chromatography of neohesperidin dihydrochalcone.", "content": "The determination of a number of impurities in neohesperidin dihydrochalcone is described, as well as the determination of neohesperidin dihydrochalcone in food products. A reversed-phase chromatographic system is used, with octadecyltrichloro-silane-treated silica gel as chemically bonded stationary phase and methanol-water as mobile phase; a detailed procedure for preparing the packing material is given, and the dependence of the amount of bonded stationary phase on the humidity of the silica gel before the bonding reaction is shown. The glass column was packed at 350 atm in a steel pressure vessel, with use of a slurry-packing technique; details are given of the pressure vessel and of the packing method. Chromatograms are reproduced to show the performance of such columns in this type of analysis.", "contents": "Liquid chromatography of neohesperidin dihydrochalcone. The determination of a number of impurities in neohesperidin dihydrochalcone is described, as well as the determination of neohesperidin dihydrochalcone in food products. A reversed-phase chromatographic system is used, with octadecyltrichloro-silane-treated silica gel as chemically bonded stationary phase and methanol-water as mobile phase; a detailed procedure for preparing the packing material is given, and the dependence of the amount of bonded stationary phase on the humidity of the silica gel before the bonding reaction is shown. The glass column was packed at 350 atm in a steel pressure vessel, with use of a slurry-packing technique; details are given of the pressure vessel and of the packing method. Chromatograms are reproduced to show the performance of such columns in this type of analysis."}
{"id": "PMID:187611", "title": "Presence of H-Y antigen and testis in 46, XX true hermaphroditism, evidence for Y-chromosomal function.", "content": "Endocrinologic and serologic studies of a 2-year-old child with the chromosomal complement 46,XX and ambiguous genitalia suggested the preoperative diagnosis of true hermaphroditism. Urinary and serum androgen production in response to human chorionic gonadotrophin was in the range expected for normal males, implying presence of cryptic testicular tissue. Moreover, detection of H-Y antigen, a cell surface component associated with testicular differentiation and coded or regulated by a Y-chromosomal gene, indicated presence of Y-chromosomal material. The diagnosis of true hermaphroditism was confirmed at surgery. Assuming a constant association of H-Y antigen and testicular differentiation is established, human H-Y serology may be an important adjunct to the endocrinologic evaluation of intersex patients. Our studies support the interpretation that a Y-chromosomal translocation too small for cytologic detection accounts for testicular differentiation in 46,XX true hermaphroditism. Expression of H-Y antigen remained positive after castration.", "contents": "Presence of H-Y antigen and testis in 46, XX true hermaphroditism, evidence for Y-chromosomal function. Endocrinologic and serologic studies of a 2-year-old child with the chromosomal complement 46,XX and ambiguous genitalia suggested the preoperative diagnosis of true hermaphroditism. Urinary and serum androgen production in response to human chorionic gonadotrophin was in the range expected for normal males, implying presence of cryptic testicular tissue. Moreover, detection of H-Y antigen, a cell surface component associated with testicular differentiation and coded or regulated by a Y-chromosomal gene, indicated presence of Y-chromosomal material. The diagnosis of true hermaphroditism was confirmed at surgery. Assuming a constant association of H-Y antigen and testicular differentiation is established, human H-Y serology may be an important adjunct to the endocrinologic evaluation of intersex patients. Our studies support the interpretation that a Y-chromosomal translocation too small for cytologic detection accounts for testicular differentiation in 46,XX true hermaphroditism. Expression of H-Y antigen remained positive after castration."}
{"id": "PMID:187612", "title": "Evidence for an unidentified ACTH-induced steroid hormone causing hypertension.", "content": "The hypothesis that hyperaldosteronism is not the sole cause of hypertension in dexamethasone-suppressible hyperaldosteronsim was tested in an 18-year-old male. After six years of little or no treatment, the hypertension and mild hyperaldosteronism were promptly decreased by a small dose of dexamethasone. During dexamethasone treatment, when aldosterone secretion was suppressed to less than normal and he was normotensive, steroids were given by constant infusion in an attempt to reproduce the hypertension of the dexamethasone-free state. Neither five days of aldosterone or 18-hydroxydesoxycorticosterone (18-OH-DOC) at 1 mg/day, nor desoxycorticosterone (DOC) at 30 mg/day caused hypertension. However, sodium retention and potassium loss was observed during aldosterone and DOC infusion. Hypertension was produced within five days during infusion with ACTH or oral metyrapone. The hypertensive effect of the latter was abolished by addition of aminoglutethimide treatment. These studies suggest that a steroid other than aldosterone, 18-OH-DOC, or DOC may be the cause of the ACTH-induced hypertension in this patient. The aminoglutethimide data suggest that the ACTH effect on blood pressure is due to a steroid, and the metyrapone studies suggest that the steroid may be an 11-desoxysteroid. Urine and blood collected under ACTH stimulation and metyrapone treatment may be a rich source from which we may characterize this hormone.", "contents": "Evidence for an unidentified ACTH-induced steroid hormone causing hypertension. The hypothesis that hyperaldosteronism is not the sole cause of hypertension in dexamethasone-suppressible hyperaldosteronsim was tested in an 18-year-old male. After six years of little or no treatment, the hypertension and mild hyperaldosteronism were promptly decreased by a small dose of dexamethasone. During dexamethasone treatment, when aldosterone secretion was suppressed to less than normal and he was normotensive, steroids were given by constant infusion in an attempt to reproduce the hypertension of the dexamethasone-free state. Neither five days of aldosterone or 18-hydroxydesoxycorticosterone (18-OH-DOC) at 1 mg/day, nor desoxycorticosterone (DOC) at 30 mg/day caused hypertension. However, sodium retention and potassium loss was observed during aldosterone and DOC infusion. Hypertension was produced within five days during infusion with ACTH or oral metyrapone. The hypertensive effect of the latter was abolished by addition of aminoglutethimide treatment. These studies suggest that a steroid other than aldosterone, 18-OH-DOC, or DOC may be the cause of the ACTH-induced hypertension in this patient. The aminoglutethimide data suggest that the ACTH effect on blood pressure is due to a steroid, and the metyrapone studies suggest that the steroid may be an 11-desoxysteroid. Urine and blood collected under ACTH stimulation and metyrapone treatment may be a rich source from which we may characterize this hormone."}
{"id": "PMID:187613", "title": "Nonautonomous function of a pancreatic insulinoma.", "content": "A 56-year-old woman with symptoms of weakness, visual blurring, and sweating underwent diagnostic studies to evaluate the etiology of her hypoglycemia. Fasting hypoglycemia was never documented; in diagnostic studies performed during her two hospitalizations and several outpatient glucose tolerance tests, the lowest fasting plasma glucose recorded was 56 mg/dl. The patient displayed exaggerated plasma insulin responses following oral glucose (peak response: 447 muU/ml at 30 min) and following 1 gm of iv tolbutamide (peak response: 719 muU/ml at 5 min) with symptomatic profound hypoglyceria during both tests. Basal per cent proinsulin was elevated at 49% (normal range 5-22%). Throughout a 72 h fast, values for plasma glucose, insulin, and glucose/insulin ratios were all within the normal range. During the infusion of exogenous insulin (0.1 U/kg for 60 min) serum C-peptide reactivity suppressed to less than 1.3 ng/ml when the plasma glucose fell below 40 mg/dl representing normal suppression. At surgery, a pancreatic beta cell adenoma was found and removed. This patient represents the uncommon circumstances in which stimulation tests with tolbutamide and glucose were more helpful in establishing a preoperative diagnosis than were the suppression tests.", "contents": "Nonautonomous function of a pancreatic insulinoma. A 56-year-old woman with symptoms of weakness, visual blurring, and sweating underwent diagnostic studies to evaluate the etiology of her hypoglycemia. Fasting hypoglycemia was never documented; in diagnostic studies performed during her two hospitalizations and several outpatient glucose tolerance tests, the lowest fasting plasma glucose recorded was 56 mg/dl. The patient displayed exaggerated plasma insulin responses following oral glucose (peak response: 447 muU/ml at 30 min) and following 1 gm of iv tolbutamide (peak response: 719 muU/ml at 5 min) with symptomatic profound hypoglyceria during both tests. Basal per cent proinsulin was elevated at 49% (normal range 5-22%). Throughout a 72 h fast, values for plasma glucose, insulin, and glucose/insulin ratios were all within the normal range. During the infusion of exogenous insulin (0.1 U/kg for 60 min) serum C-peptide reactivity suppressed to less than 1.3 ng/ml when the plasma glucose fell below 40 mg/dl representing normal suppression. At surgery, a pancreatic beta cell adenoma was found and removed. This patient represents the uncommon circumstances in which stimulation tests with tolbutamide and glucose were more helpful in establishing a preoperative diagnosis than were the suppression tests."}
{"id": "PMID:187614", "title": "Urinary cyclic nucleotide levels in patients with hyper- and hypothyroidism.", "content": "Urinary cyclic AMP, cyclic GMP and creatinine excretion were measured in 38 patients with hyperthyroidism, 32 patients with hypothyroidism and in 57 normal subjects. The excretion of both cyclic nucleotides was significantly increased in hyperthyroid females, but not in hyperthyroid males. The cyclic nucleotides/creatinine ratios, however, were uniformly elevated in both male and female hyperthyroid subjects and this was due, in part, to decreased creatinine excretion. Cyclic AMP excretion was significantly decreased in the hypothyroid subjects, but the cyclic AMP/creatinine ratios were not significantly different from normal. There were no significant alterations in cyclic GMP and cyclic GMP/creatinine ratios in the male hypothyroid patients, but ratios in the female patients were slightly greater than in the normals. These results demonstrate that hyper- and hypothyroidism may be associated with appreciable alterations in urinary cyclic nucleotide levels and that there may be sex-related differences in the patterns of urinary excretion of these nucleotides. The cyclic nucleotide levels herein described in patients with hyper- and hypothyroidism are qualitatively and, in some instances, quantitatively similar to those found in patients with hyper- and hypoparathyroidism, respectively.", "contents": "Urinary cyclic nucleotide levels in patients with hyper- and hypothyroidism. Urinary cyclic AMP, cyclic GMP and creatinine excretion were measured in 38 patients with hyperthyroidism, 32 patients with hypothyroidism and in 57 normal subjects. The excretion of both cyclic nucleotides was significantly increased in hyperthyroid females, but not in hyperthyroid males. The cyclic nucleotides/creatinine ratios, however, were uniformly elevated in both male and female hyperthyroid subjects and this was due, in part, to decreased creatinine excretion. Cyclic AMP excretion was significantly decreased in the hypothyroid subjects, but the cyclic AMP/creatinine ratios were not significantly different from normal. There were no significant alterations in cyclic GMP and cyclic GMP/creatinine ratios in the male hypothyroid patients, but ratios in the female patients were slightly greater than in the normals. These results demonstrate that hyper- and hypothyroidism may be associated with appreciable alterations in urinary cyclic nucleotide levels and that there may be sex-related differences in the patterns of urinary excretion of these nucleotides. The cyclic nucleotide levels herein described in patients with hyper- and hypothyroidism are qualitatively and, in some instances, quantitatively similar to those found in patients with hyper- and hypoparathyroidism, respectively."}
{"id": "PMID:187615", "title": "Lithium does not inhibit the parathyroid hormone-mediated rise in urinary cyclic AMP and phosphate in humans.", "content": "To test the hypothesis that lithium is a general inhibitor of hormone-activated adenylate cyclase, we infuse parathyroid hormone (PTH) into human subjects prior to and during lithium carbonate administration. PTH infusion caused a significant increase in urinary cyclic AMP and urinary phosphate excretion. There was no significant difference in these responses in the lithium compared to the control period. In four patients with primary hyperparathyroidism, lithium had no significant effect on serum calcium or phosphate or on tubular reabsorption of phosphate. The data do not substantiate the hypothesis that lithium (at therapeutic concentrations) is a general inhibitor of hormonally-activated adenylate cyclase, nor do they support its potential clinical utility in primary hyperparthyroidism.", "contents": "Lithium does not inhibit the parathyroid hormone-mediated rise in urinary cyclic AMP and phosphate in humans. To test the hypothesis that lithium is a general inhibitor of hormone-activated adenylate cyclase, we infuse parathyroid hormone (PTH) into human subjects prior to and during lithium carbonate administration. PTH infusion caused a significant increase in urinary cyclic AMP and urinary phosphate excretion. There was no significant difference in these responses in the lithium compared to the control period. In four patients with primary hyperparathyroidism, lithium had no significant effect on serum calcium or phosphate or on tubular reabsorption of phosphate. The data do not substantiate the hypothesis that lithium (at therapeutic concentrations) is a general inhibitor of hormonally-activated adenylate cyclase, nor do they support its potential clinical utility in primary hyperparthyroidism."}
{"id": "PMID:187616", "title": "A low molecular weight substance obtained from serum which has luteinizing hormone like activity (\"mini LH\").", "content": "A low molecular weight substance of 1000-2000 daltons has been isolated in dialysates of normal human serum which, on testing in a radio-immunoassay, a radioligand receptorassay and an in-vitro bioassay exhibited LH activity comparable to the range of LH activity found in normal serum. The substance was heat labile. Its reactivity in a RIA suggests peptide nature. No \"mini LH\" activity could be derived from LH-free serum samples of hypophysectomized patients.", "contents": "A low molecular weight substance obtained from serum which has luteinizing hormone like activity (\"mini LH\"). A low molecular weight substance of 1000-2000 daltons has been isolated in dialysates of normal human serum which, on testing in a radio-immunoassay, a radioligand receptorassay and an in-vitro bioassay exhibited LH activity comparable to the range of LH activity found in normal serum. The substance was heat labile. Its reactivity in a RIA suggests peptide nature. No \"mini LH\" activity could be derived from LH-free serum samples of hypophysectomized patients."}
{"id": "PMID:187617", "title": "Improved rubella hemagglutination inhibtion test: inactivation of non-immunoglobulin hemagglutination inhibitors by phospholipase C.", "content": "A method using phospholipase C (PL-C) for removing nonspecific inhibitors (NSI) of rubella virus hemagglutinin is described. PL-C was found to hydrolyze NSI without altering the hemagglutination inhibition (HI) activity of the specific antibody and could be used to remove NSI in the rubella HI test by using formalinized erythrocytes, which resisted the enzymatic action; fresh erythrocytes were lysed by PL-C. The HI test using PL-C treated sera gave true measurements of actual rubella antibody content, and HI titers of PL-C treated sera were identical or equivalent (+/-1 dilution) to those of sera treated with dextran sulfate and CaCl2 (DS-C). Thus, the PL-C method gave results as reproducible and reliable as the DS-C method and was more convenient.", "contents": "Improved rubella hemagglutination inhibtion test: inactivation of non-immunoglobulin hemagglutination inhibitors by phospholipase C. A method using phospholipase C (PL-C) for removing nonspecific inhibitors (NSI) of rubella virus hemagglutinin is described. PL-C was found to hydrolyze NSI without altering the hemagglutination inhibition (HI) activity of the specific antibody and could be used to remove NSI in the rubella HI test by using formalinized erythrocytes, which resisted the enzymatic action; fresh erythrocytes were lysed by PL-C. The HI test using PL-C treated sera gave true measurements of actual rubella antibody content, and HI titers of PL-C treated sera were identical or equivalent (+/-1 dilution) to those of sera treated with dextran sulfate and CaCl2 (DS-C). Thus, the PL-C method gave results as reproducible and reliable as the DS-C method and was more convenient."}
{"id": "PMID:187618", "title": "Sensitivity of a radioimmunoassay method for detection of certain viral antibodies in sera and cerebrospinal fluids.", "content": "An indirect solid-phase radioimmunoassay (RIA) was applied to titration of serum and cerebrospinal fluid (CSF) antibodies against a variety of viruses including rubella, mumps, measles, herpes simplex, varicella-zoster, and vaccinia. The test used fixed, virus-infected cells as a source of antigen, and conditions for optimal production of viral antigen were determined for each virus-host cell system. In acute, uncomplicated viral infections, sera taken 2 to 5 days after onset generally had low homotypic RIA titers ranging from less than 1:100 to 1:500, whereas convalescent-phase titers ranged from 1:128,000 to 1:512,000. Rubella and measles antibody titers as high as 1:256,000 were demonstrated by RIA in CSF from patients with chronic panencephalitis, whereas homologous antibody titers of 1:4,000 were detected in CSF from acute mumps, herpes simplex, and varicella-zoster virus infections with central nervous system involvement. Some heterotypic antibody was demonstrable by RIA in CSF, but, with the exception of herpes simplex antibody in a mumps virus infection, titers were markedly lower than those to the infecting virus type. RIA generally demonstrated titers at least 1,000 times higher than those obtained by conventional assays such as complement fixation, hemagglutination inhibition, neutralization, and immunofluorescent staining.", "contents": "Sensitivity of a radioimmunoassay method for detection of certain viral antibodies in sera and cerebrospinal fluids. An indirect solid-phase radioimmunoassay (RIA) was applied to titration of serum and cerebrospinal fluid (CSF) antibodies against a variety of viruses including rubella, mumps, measles, herpes simplex, varicella-zoster, and vaccinia. The test used fixed, virus-infected cells as a source of antigen, and conditions for optimal production of viral antigen were determined for each virus-host cell system. In acute, uncomplicated viral infections, sera taken 2 to 5 days after onset generally had low homotypic RIA titers ranging from less than 1:100 to 1:500, whereas convalescent-phase titers ranged from 1:128,000 to 1:512,000. Rubella and measles antibody titers as high as 1:256,000 were demonstrated by RIA in CSF from patients with chronic panencephalitis, whereas homologous antibody titers of 1:4,000 were detected in CSF from acute mumps, herpes simplex, and varicella-zoster virus infections with central nervous system involvement. Some heterotypic antibody was demonstrable by RIA in CSF, but, with the exception of herpes simplex antibody in a mumps virus infection, titers were markedly lower than those to the infecting virus type. RIA generally demonstrated titers at least 1,000 times higher than those obtained by conventional assays such as complement fixation, hemagglutination inhibition, neutralization, and immunofluorescent staining."}
{"id": "PMID:187619", "title": "Vesicular stomatitis virus plaque production in monolayer cultures with liquid overlay medium: description and adaptation to a one-day, human interferon-plaque.", "content": "Vesicular stomatitis virus forms discrete, microscopic plaques in stationary cultures of the WISH amnion cell line. Microplaque formation is rapid, reproducible, and easily quantitated, occurs at temperatures ranging from 33 to 40 degrees C, and does not require a semisolid overlay. WISH cells, however, are less sensitive to vesicular stomatitis virus than are chicken embryo, 3T6, or Vero cells. WISH amnion cells also are highly sensitive to the antiviral effects of human interferon, and a quantitative human interferon assay, based on vesicular stomatitis virus plaque reduction in WISH cells, is described. This interferon assay can be performed within 1 day, uses a liquid overlay medium, does not require a vital stain, is as sensitive as other methods that use diploid cell strains, and is performed in a microtiter system.", "contents": "Vesicular stomatitis virus plaque production in monolayer cultures with liquid overlay medium: description and adaptation to a one-day, human interferon-plaque. Vesicular stomatitis virus forms discrete, microscopic plaques in stationary cultures of the WISH amnion cell line. Microplaque formation is rapid, reproducible, and easily quantitated, occurs at temperatures ranging from 33 to 40 degrees C, and does not require a semisolid overlay. WISH cells, however, are less sensitive to vesicular stomatitis virus than are chicken embryo, 3T6, or Vero cells. WISH amnion cells also are highly sensitive to the antiviral effects of human interferon, and a quantitative human interferon assay, based on vesicular stomatitis virus plaque reduction in WISH cells, is described. This interferon assay can be performed within 1 day, uses a liquid overlay medium, does not require a vital stain, is as sensitive as other methods that use diploid cell strains, and is performed in a microtiter system."}
{"id": "PMID:187620", "title": "Extrinsic modulation of human T-lymphocyte E rosette function associated with prolonged hepatocellular injury after viral hepatitis.", "content": "Defective T-lymphocyte E rosette (ER) function associated with viral hepatitis A and B may be due to mechanisms extrinsic or intrinsic to the target lymphocyte. The extrinsic defect is induced by an immunoregulatory plasma lipoprotein (RIF) and has the capacity to regenerate ER function in vitro. The intrinsic defect is refractory to regeneration and is not associated with RIF. Although both mechanisms occur with high frequency during the acute phase of viral hepatitis they tend to segregate in accordance with progression of hepatocellular injury at later stages of the disease. The extrinsic defect was observed in 7 out of 8 patients with longstanding chronic active hepatitis and in 10 out of 10 patients with unresolved hepatitis 12 wk after the onset of jaundice. In contrast, none of nine patients with resolved hepatitis had extrinsically defective ER function 12 wk after the onset of jaundice whereas eight of them displayed an intrinsic defect of ER function at that time. Among the various viral and liver diseases studied RIF appeared to be specific for hepatitis A and B viral infections. None of 64 sera from a variety of viral infections including Epstein-Barr virus cytomegalovirus mononucleosis with associated hepatitis nor 15 sera from patients with several chronic nonviral liver diseases were positive for RIF. RIF and its associated extrinsic defect in ER function therefore appear to correlate with a particular type of hepatocellular injury initiated by the hepatitis A and B viruses that may have a propensity for persistence and(or) progression to an aggressive form of chronic hepatitis.", "contents": "Extrinsic modulation of human T-lymphocyte E rosette function associated with prolonged hepatocellular injury after viral hepatitis. Defective T-lymphocyte E rosette (ER) function associated with viral hepatitis A and B may be due to mechanisms extrinsic or intrinsic to the target lymphocyte. The extrinsic defect is induced by an immunoregulatory plasma lipoprotein (RIF) and has the capacity to regenerate ER function in vitro. The intrinsic defect is refractory to regeneration and is not associated with RIF. Although both mechanisms occur with high frequency during the acute phase of viral hepatitis they tend to segregate in accordance with progression of hepatocellular injury at later stages of the disease. The extrinsic defect was observed in 7 out of 8 patients with longstanding chronic active hepatitis and in 10 out of 10 patients with unresolved hepatitis 12 wk after the onset of jaundice. In contrast, none of nine patients with resolved hepatitis had extrinsically defective ER function 12 wk after the onset of jaundice whereas eight of them displayed an intrinsic defect of ER function at that time. Among the various viral and liver diseases studied RIF appeared to be specific for hepatitis A and B viral infections. None of 64 sera from a variety of viral infections including Epstein-Barr virus cytomegalovirus mononucleosis with associated hepatitis nor 15 sera from patients with several chronic nonviral liver diseases were positive for RIF. RIF and its associated extrinsic defect in ER function therefore appear to correlate with a particular type of hepatocellular injury initiated by the hepatitis A and B viruses that may have a propensity for persistence and(or) progression to an aggressive form of chronic hepatitis."}
{"id": "PMID:187621", "title": "Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the idfferential diagnosis of hypercalcemia.", "content": "Urinary cyclic AMP (UcAMP) appropriate for the serum calcium concentration was determined in normal subjects during the base-line state and during alteration in their serum calcium concentrations by saline and calcium infusions. This was compared to the UcAMP in 76 patients with hypercalcemia and 5 patients with hypocalcemia. In 54 of 56 patients with primary hyperparathyroidism, the UcAMP was inappropriately high for their serum calcium concentration, the 2 exceptions having renal failure. In four patients with vitamin D intoxication, sarcoidosis, milkalkali syndrome, and thiazide-induced hypercalcemia and in five patients with hypocalcemia due to hypoparathyroidism, the UcAMP was appropriately low for their serum calcium concentration. In 16 patients with nonparathyroid neoplasms, 10 had UcAMP levels that were inappropriately high suggesting ectopic parathyroid hormone (PTH)-mediated hypercalcemia and 6 had UcAMP levels that were appropriately low suggesting that their hypercalcemia was due to osteolytic factors other than PTH. Correlations between UcAMP, serum calcium concentration, and carboxyl-terminal immunoreactive PTH suggest that random UcAMP is a sensitive accurate reflection of circulating biologically active PTH. If there is adequate renal function (serum creatinine concentration less than 2.0 mg/dl), a random UcAMP expressed as mumol/g creatinine and analyzed as a function of the serum calcium concentration completely separates patients with PTH and non-PTH-mediated hypercalcemia.", "contents": "Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the idfferential diagnosis of hypercalcemia. Urinary cyclic AMP (UcAMP) appropriate for the serum calcium concentration was determined in normal subjects during the base-line state and during alteration in their serum calcium concentrations by saline and calcium infusions. This was compared to the UcAMP in 76 patients with hypercalcemia and 5 patients with hypocalcemia. In 54 of 56 patients with primary hyperparathyroidism, the UcAMP was inappropriately high for their serum calcium concentration, the 2 exceptions having renal failure. In four patients with vitamin D intoxication, sarcoidosis, milkalkali syndrome, and thiazide-induced hypercalcemia and in five patients with hypocalcemia due to hypoparathyroidism, the UcAMP was appropriately low for their serum calcium concentration. In 16 patients with nonparathyroid neoplasms, 10 had UcAMP levels that were inappropriately high suggesting ectopic parathyroid hormone (PTH)-mediated hypercalcemia and 6 had UcAMP levels that were appropriately low suggesting that their hypercalcemia was due to osteolytic factors other than PTH. Correlations between UcAMP, serum calcium concentration, and carboxyl-terminal immunoreactive PTH suggest that random UcAMP is a sensitive accurate reflection of circulating biologically active PTH. If there is adequate renal function (serum creatinine concentration less than 2.0 mg/dl), a random UcAMP expressed as mumol/g creatinine and analyzed as a function of the serum calcium concentration completely separates patients with PTH and non-PTH-mediated hypercalcemia."}
{"id": "PMID:187622", "title": "Superoxide production and reducing activity in human platelets.", "content": "Human platelets contain the cuprozinc (cytoplasmic) and manganese (mitochondrial) forms of superoxide dismutase. Nevertheless, superoxide radicals were detectable in the surrounding medium of metabolically viable platelet suspensions by using two assay systems: cytochrome c and nitroblue tetrazolium. The quantity of superoxide generated by platelets (5 X 10(5) superoxide radicals/platelet per 10 min) was constant and did not increase after aggregation by agents such as collagen and thrombin. The superoxide-generating system was present in the supernate of both aggregated and resting platelets and therefore was not platelet-bound. Platelet superoxide production was unaffected by prior ingestion of aspirin, indicating that the prostaglandin and thromboxane pathways were not involved. Both resting and aggregated platelets exhibited a reductive capacity toward cytochrome c and nitroblue tetrazolium which was unrelated to superoxide production. Furthermore, the aggregation process always resulted in a marked increase in this reduction. The nonsuperoxide reduction associated with aggregation was found to be membrane bound and to decrease with an apparent first order reaction rate (k1 = 0.067 min-1). In addition, accumulative, time-dependent nonsuperoxide-related cytochrome c reduction was also detected. Since there is no superoxide dismutase in plasma, the presence of superoxide radicals in the surrounding medium of platelets may have in vitro significance for platelet and leukocyte concentration and storage and in vivo significance for hemostasis, coagulation, and thrombosis. The nonsuperoxide-related reducing activities may represent a biochemical basis for platelet-blood vessel interactions, with particular reference to blood vessel integrity.", "contents": "Superoxide production and reducing activity in human platelets. Human platelets contain the cuprozinc (cytoplasmic) and manganese (mitochondrial) forms of superoxide dismutase. Nevertheless, superoxide radicals were detectable in the surrounding medium of metabolically viable platelet suspensions by using two assay systems: cytochrome c and nitroblue tetrazolium. The quantity of superoxide generated by platelets (5 X 10(5) superoxide radicals/platelet per 10 min) was constant and did not increase after aggregation by agents such as collagen and thrombin. The superoxide-generating system was present in the supernate of both aggregated and resting platelets and therefore was not platelet-bound. Platelet superoxide production was unaffected by prior ingestion of aspirin, indicating that the prostaglandin and thromboxane pathways were not involved. Both resting and aggregated platelets exhibited a reductive capacity toward cytochrome c and nitroblue tetrazolium which was unrelated to superoxide production. Furthermore, the aggregation process always resulted in a marked increase in this reduction. The nonsuperoxide reduction associated with aggregation was found to be membrane bound and to decrease with an apparent first order reaction rate (k1 = 0.067 min-1). In addition, accumulative, time-dependent nonsuperoxide-related cytochrome c reduction was also detected. Since there is no superoxide dismutase in plasma, the presence of superoxide radicals in the surrounding medium of platelets may have in vitro significance for platelet and leukocyte concentration and storage and in vivo significance for hemostasis, coagulation, and thrombosis. The nonsuperoxide-related reducing activities may represent a biochemical basis for platelet-blood vessel interactions, with particular reference to blood vessel integrity."}
{"id": "PMID:187623", "title": "High affinity binding of 125I-angiotensin II to rat glomerular basement membranes.", "content": "125I-angiotensin II (AII) specifically bound to rat glomerular basement membrane (GBM). The kinetics of binding were similar to those obtained with the total glomeruli. The apparent dissociation constant was close to 50 pM with both preparations. The number of sites related to the amount of protein was two times greater with GBM than with total glomeruli. Since the amount of GBM protein extracted from a given amount of glomerular protein was about 10%, it was possible to estimate the share of the GBM binding sites for AII as representing 20% of the total number present in the entire glomerulus. Binding studies at equilibrium as a function of 125I-AII concentration and competitive binding experiments suggested either multiplicity of the binding sites or cooperativity in the binding reaction. Degradation of 125I-AII in the presence of GBM was slight and did not increase with time. The difference in the degrees of degradation of 125I-AII was too small to account for the observed difference in binding when the results obtained with GBM and isolated glomeruli preparations were compared. 125I-AII binding to GBM was increased after treatment of these membranes with collagenase, slightly diminished with neuraminidase, and almost completely abolished with trypsin suggesting the proteic nature of the receptor. 125I-AII binding to GBM was diminished after incubation of GBM with anti-GBM antibodies as a result of a decrease in the number of binding sites. 125I-AII binding was even more diminished in preparations of glomeruli isolated from rats passively immunized with anti-GBM antibodies when compared with glomeruli from control animals. This resulted from both smaller affinity for AII and decrease in the number of the binding sites. The present data provides evidence for specific binding sites for AII localized on GBM. This is noteworthy since receptors for polypeptide hormones are currently observed on the surface of cell membranes. These findings also suggest a new physiological role for AII which might involve modification of GBM permeability.", "contents": "High affinity binding of 125I-angiotensin II to rat glomerular basement membranes. 125I-angiotensin II (AII) specifically bound to rat glomerular basement membrane (GBM). The kinetics of binding were similar to those obtained with the total glomeruli. The apparent dissociation constant was close to 50 pM with both preparations. The number of sites related to the amount of protein was two times greater with GBM than with total glomeruli. Since the amount of GBM protein extracted from a given amount of glomerular protein was about 10%, it was possible to estimate the share of the GBM binding sites for AII as representing 20% of the total number present in the entire glomerulus. Binding studies at equilibrium as a function of 125I-AII concentration and competitive binding experiments suggested either multiplicity of the binding sites or cooperativity in the binding reaction. Degradation of 125I-AII in the presence of GBM was slight and did not increase with time. The difference in the degrees of degradation of 125I-AII was too small to account for the observed difference in binding when the results obtained with GBM and isolated glomeruli preparations were compared. 125I-AII binding to GBM was increased after treatment of these membranes with collagenase, slightly diminished with neuraminidase, and almost completely abolished with trypsin suggesting the proteic nature of the receptor. 125I-AII binding to GBM was diminished after incubation of GBM with anti-GBM antibodies as a result of a decrease in the number of binding sites. 125I-AII binding was even more diminished in preparations of glomeruli isolated from rats passively immunized with anti-GBM antibodies when compared with glomeruli from control animals. This resulted from both smaller affinity for AII and decrease in the number of the binding sites. The present data provides evidence for specific binding sites for AII localized on GBM. This is noteworthy since receptors for polypeptide hormones are currently observed on the surface of cell membranes. These findings also suggest a new physiological role for AII which might involve modification of GBM permeability."}
{"id": "PMID:187624", "title": "In vivo effect of indomethacin to potentiate the renal medullary cyclic AMP response to vasopressin.", "content": "In a previous study we demonstrated that indomethacin potentiated the hydro-osmotic action of vasopressin in vivo. It was hypothesized that this action of indomethacin was due to its ability to suppress renal medullary prostaglandin synthesis, since in vitro studies have suggested that prostaglandins interfere with the ability of vasopressin to stimulate production of its intracellular mediator, cyclic AMP. In the present study this hypothesis was tested in vivo. Anesthetized rats undergoing a water diuresis were studied. In a control group, bolus injections of 200 muU of vasopressin caused a rise in urinary osmolality (Uosm) from 124 +/- 6 to 253 +/- 20 mosmol/kg H2O (P less than 0.005). In a group treated with 2 mg/kg of indomethacin the same dose of vasopressin caused a significantly greater (P less than 0.001) rise in Uosm from 124 +/- 7 to 428 +/- 19 mosmol/kg H2O. Medullary tissue cyclic AMP rose from 9.4 +/- 0.9 to 13.4 +/- 1.7 (P less than 0.05) pmol/mg tissue protein after vasopressin administration in animals receiving no indomethacin, while in indomethacin-treated animals there was a significantly greater rise (P less than 0.001) in medullary cyclic AMP from 10.4 +/- 0.9 to 21.6 +/- 2.1 pmol/mg tissue protein in response to the vasopressin injections. In neither control animals nor indomethacin-treated animals were there significant changes in renal hemodynamics, as measured by clearance techniques. Indomethacin, when given alone, had no effect on Uosm or medullary tissue cyclic AMP. Indomethacin did, however, reduce medullary prostaglandin E content from 84.7 +/- 15.0 to 15.6 +/- 4.3 pg/mg tissue. This study has shown that indomethacin, in a dose which suppresses medullary prostaglandin content, potentiates the ability of vasopressin to increase the tissue content of its intracellular mediator, cyclic AMP. Indomethacin caused no demonstrable inhibition of cyclic AMP phosphodiesterase. Therefore, it seems likely that indomethacin enhanced the ability of vasopressin to increase medullary cyclic AMP levels by causing an increased production rather than decreased destruction of the nucleotide. We conclude that this action of indomethacin contributes to its ability to potentiate the hydro-osmotic action of vasopressin in vivo. A corollary to this conclusion is that endogenous medullary prostaglandin E's may be significant physiological modulators of the renal response to vasopressin.", "contents": "In vivo effect of indomethacin to potentiate the renal medullary cyclic AMP response to vasopressin. In a previous study we demonstrated that indomethacin potentiated the hydro-osmotic action of vasopressin in vivo. It was hypothesized that this action of indomethacin was due to its ability to suppress renal medullary prostaglandin synthesis, since in vitro studies have suggested that prostaglandins interfere with the ability of vasopressin to stimulate production of its intracellular mediator, cyclic AMP. In the present study this hypothesis was tested in vivo. Anesthetized rats undergoing a water diuresis were studied. In a control group, bolus injections of 200 muU of vasopressin caused a rise in urinary osmolality (Uosm) from 124 +/- 6 to 253 +/- 20 mosmol/kg H2O (P less than 0.005). In a group treated with 2 mg/kg of indomethacin the same dose of vasopressin caused a significantly greater (P less than 0.001) rise in Uosm from 124 +/- 7 to 428 +/- 19 mosmol/kg H2O. Medullary tissue cyclic AMP rose from 9.4 +/- 0.9 to 13.4 +/- 1.7 (P less than 0.05) pmol/mg tissue protein after vasopressin administration in animals receiving no indomethacin, while in indomethacin-treated animals there was a significantly greater rise (P less than 0.001) in medullary cyclic AMP from 10.4 +/- 0.9 to 21.6 +/- 2.1 pmol/mg tissue protein in response to the vasopressin injections. In neither control animals nor indomethacin-treated animals were there significant changes in renal hemodynamics, as measured by clearance techniques. Indomethacin, when given alone, had no effect on Uosm or medullary tissue cyclic AMP. Indomethacin did, however, reduce medullary prostaglandin E content from 84.7 +/- 15.0 to 15.6 +/- 4.3 pg/mg tissue. This study has shown that indomethacin, in a dose which suppresses medullary prostaglandin content, potentiates the ability of vasopressin to increase the tissue content of its intracellular mediator, cyclic AMP. Indomethacin caused no demonstrable inhibition of cyclic AMP phosphodiesterase. Therefore, it seems likely that indomethacin enhanced the ability of vasopressin to increase medullary cyclic AMP levels by causing an increased production rather than decreased destruction of the nucleotide. We conclude that this action of indomethacin contributes to its ability to potentiate the hydro-osmotic action of vasopressin in vivo. A corollary to this conclusion is that endogenous medullary prostaglandin E's may be significant physiological modulators of the renal response to vasopressin."}
{"id": "PMID:187626", "title": "Blocking of catecholamine activation of adenylate cyclase by N, N'dicyclohexyl carbodiimide in turkey erythrocytes.", "content": "Incubation of erythrocytes or their isolated membranes with N, N'dicyclohexyl carbodiimide (DCC) blocked isoproterenol activation of the adenylate cyclase. Fluoride activation remained unaffected. L-epinephrine and DL-propranolol partially and transiently protected the system against DCC. D-Epinephrine and dopamine did not protect. The enzyme system preactivated by isoproterenol plus Gpp(NH)p was no longer sensitive to DCC. In contrast to the water insoluble DCC, a water soluble carbodiimide acted only at high concentration and blocked fluoride as well as catecholamine activation of the adenylate cyclase. The findings indicate that DCC attacks a group on, or near, the beta-adrenergic receptor and that this group is located in a hydrophobic region of the cell membrane. It is argued that a low nominal concentration of DCC in the aqueous suspension of erythrocytes actually represents a very high concentration of DCC in the hydrophobic region of the cell membranes, near the beta-adrenergic receptor. The reaction with DCC may prove to be a useful tool in future analyses of beta-adrenergic receptor function.", "contents": "Blocking of catecholamine activation of adenylate cyclase by N, N'dicyclohexyl carbodiimide in turkey erythrocytes. Incubation of erythrocytes or their isolated membranes with N, N'dicyclohexyl carbodiimide (DCC) blocked isoproterenol activation of the adenylate cyclase. Fluoride activation remained unaffected. L-epinephrine and DL-propranolol partially and transiently protected the system against DCC. D-Epinephrine and dopamine did not protect. The enzyme system preactivated by isoproterenol plus Gpp(NH)p was no longer sensitive to DCC. In contrast to the water insoluble DCC, a water soluble carbodiimide acted only at high concentration and blocked fluoride as well as catecholamine activation of the adenylate cyclase. The findings indicate that DCC attacks a group on, or near, the beta-adrenergic receptor and that this group is located in a hydrophobic region of the cell membrane. It is argued that a low nominal concentration of DCC in the aqueous suspension of erythrocytes actually represents a very high concentration of DCC in the hydrophobic region of the cell membranes, near the beta-adrenergic receptor. The reaction with DCC may prove to be a useful tool in future analyses of beta-adrenergic receptor function."}
{"id": "PMID:187627", "title": "Changes in trout testis cyclic GMP concentration during hormonally induced spermatogenesis.", "content": "The concentration of cyclic GMP was determined in trout testes (Salmo gairdnerii) during hormonally-induced sermatogenesis. Early in spermatogenesis, a relatively high concentration (1 mumole/kg wet weight testis) of cyclic GMP was present. A sharp, ten-fold, decrease in testis cyclic GMP concentration occurred during the early stages of rapid mitotic activity and testis growth. A further gradual five-fold decrease in cyclic GMP concentration occurred during meiosis and the following transformation of spermatocytes into spermatids and then to mature spermatozoa.", "contents": "Changes in trout testis cyclic GMP concentration during hormonally induced spermatogenesis. The concentration of cyclic GMP was determined in trout testes (Salmo gairdnerii) during hormonally-induced sermatogenesis. Early in spermatogenesis, a relatively high concentration (1 mumole/kg wet weight testis) of cyclic GMP was present. A sharp, ten-fold, decrease in testis cyclic GMP concentration occurred during the early stages of rapid mitotic activity and testis growth. A further gradual five-fold decrease in cyclic GMP concentration occurred during meiosis and the following transformation of spermatocytes into spermatids and then to mature spermatozoa."}
{"id": "PMID:187628", "title": "The molecular structure of the free acid of guanosine 3',5'-cyclic monophosphate (cyclic GMP).", "content": "The structure of the free acid of guanosine 3',5'-cyclic monophosphate has been determined from three dimensional x-ray diffraction data collected with a GE XRD-490 automated diffractiometer. The molecule crystallizes in the orthorhobic space group P212121 with a = 17.953(17), b = 7.530(7), and c = 12.755(12) and Z = 4. The structure was solved by direct methods. The 969 independent data were defined by full matrix least-squares to a final agreement factor, RF, of .050 for FO greater than sigma (FO). The compound exists as a switterion in the solid state. N(7) of the base is protonated. The structure of the free acid is similar to that of the sodium salt. Both have the syn conformation. The puckering of the sugar rings is also similar. Small differences exist in the bond angles of the cyclic phosphate and furanose rings.", "contents": "The molecular structure of the free acid of guanosine 3',5'-cyclic monophosphate (cyclic GMP). The structure of the free acid of guanosine 3',5'-cyclic monophosphate has been determined from three dimensional x-ray diffraction data collected with a GE XRD-490 automated diffractiometer. The molecule crystallizes in the orthorhobic space group P212121 with a = 17.953(17), b = 7.530(7), and c = 12.755(12) and Z = 4. The structure was solved by direct methods. The 969 independent data were defined by full matrix least-squares to a final agreement factor, RF, of .050 for FO greater than sigma (FO). The compound exists as a switterion in the solid state. N(7) of the base is protonated. The structure of the free acid is similar to that of the sodium salt. Both have the syn conformation. The puckering of the sugar rings is also similar. Small differences exist in the bond angles of the cyclic phosphate and furanose rings."}
{"id": "PMID:187629", "title": "Reactions in glass ionomer cements: V. Effect of incorporating tartaric acid in the cement liquid.", "content": "A description is give of the effect on the ASPA cement reaction of tartaric acid incorporated in the cement liquid. Tartaric acid acts as an accelerator that aids in the extraction of ions from the aluminosilicate glass and facilitates their binding to the polyanion chains. Postgelation hardening is significantly increased. Working time is unaffected possibly because cations are initially present as complexes.", "contents": "Reactions in glass ionomer cements: V. Effect of incorporating tartaric acid in the cement liquid. A description is give of the effect on the ASPA cement reaction of tartaric acid incorporated in the cement liquid. Tartaric acid acts as an accelerator that aids in the extraction of ions from the aluminosilicate glass and facilitates their binding to the polyanion chains. Postgelation hardening is significantly increased. Working time is unaffected possibly because cations are initially present as complexes."}
{"id": "PMID:187630", "title": "Glass ionomer cements: chemistry of erosion.", "content": "A three-month study of the chemistry of the water erosion of two forms of ASPA cement has been made. The effect of varying cement consistency and cure time was investigated. The results are discussed in terms of the known chemistry and structure of the cement. The erosion behavior is compared to that of silicate, silicophosphate, and zinc polycarboxylate dental cements. The state of absorbed water and the mechanism of erosion is discussed.", "contents": "Glass ionomer cements: chemistry of erosion. A three-month study of the chemistry of the water erosion of two forms of ASPA cement has been made. The effect of varying cement consistency and cure time was investigated. The results are discussed in terms of the known chemistry and structure of the cement. The erosion behavior is compared to that of silicate, silicophosphate, and zinc polycarboxylate dental cements. The state of absorbed water and the mechanism of erosion is discussed."}
{"id": "PMID:187631", "title": "Some characteristics of collagenase activity in gingival crevicular fluid and its relationship to gingival diseases in humans.", "content": "Collagenase activity in human gingival fluid was measured using a radioactive collagen fibril assay. The activity was positively correlated with the severity of gingival disease. The fluid collagenase seemed to be controlled by alpha 2-macroglobulin, based on its activation by NaSCN, and to be present solely in the extracellular fraction. Examination of the collagen breakdown products by acrylamide gel electrophoresis indicated that the fluid collagenase was of tissue rather than bacterial origin.", "contents": "Some characteristics of collagenase activity in gingival crevicular fluid and its relationship to gingival diseases in humans. Collagenase activity in human gingival fluid was measured using a radioactive collagen fibril assay. The activity was positively correlated with the severity of gingival disease. The fluid collagenase seemed to be controlled by alpha 2-macroglobulin, based on its activation by NaSCN, and to be present solely in the extracellular fraction. Examination of the collagen breakdown products by acrylamide gel electrophoresis indicated that the fluid collagenase was of tissue rather than bacterial origin."}
{"id": "PMID:187637", "title": "Physiological learning theory.", "content": "Attention or \"concentration\" requires control of activity in those excess neurons that are not necessary for the present task. The control is probably not a massive inhibitory suppression but may be a recruiting process, a function of complex perceptual and associative learning that begins with early experience. Inhibition, however, may still be of crucial importance as a sharpener of associative mechanisms, and the child with minimal brain damage may have suffered a selective loss of inhibitory neurons.", "contents": "Physiological learning theory. Attention or \"concentration\" requires control of activity in those excess neurons that are not necessary for the present task. The control is probably not a massive inhibitory suppression but may be a recruiting process, a function of complex perceptual and associative learning that begins with early experience. Inhibition, however, may still be of crucial importance as a sharpener of associative mechanisms, and the child with minimal brain damage may have suffered a selective loss of inhibitory neurons."}
{"id": "PMID:187638", "title": "Melanotic neuroectodermal tumor of infancy: review of the literature and report of case.", "content": "A characteristic case of melanotic neuroectodermal tumor of infancy is reported and the literature regarding this lesion is reviewed. The case reported shows the salient features of previously described melanotic neuroectodermal tumors of infancy; it occurs in infants of less than 1 year of age; it most commonly arises from bone (jaws and skull), has distinctive gross and histologic features, is benign, and is cured by total local excision. Since the teeth in the mandible and maxilla are undergoing development about the time that this tumor occurs, it is not surprising to find tooth buds in close proximity to the expanding neoplastic mass. When odontogenic rests are found in association with the lesion, it must be assumed that it is a collision of the two structures and not that the odontogenic epithelium is the origin for the lesion as previously thought. This is especially true since odontogenic epithelium is not found in the tumor when it occurs outside the jaws. This is the type of lesion that will most probably first be noticed by a dentist and should be managed by the oral surgeon. It is important to note that proper advice regarding future dental problems should be given to the parents of the infant. Such possibilities as crowding or absence of the deciduous or permanent teeth, malocclusion, and possible malformation of the remaining maxillary ridge should be explained. Close dental follow-up is mandatory since recurrence is possible.", "contents": "Melanotic neuroectodermal tumor of infancy: review of the literature and report of case. A characteristic case of melanotic neuroectodermal tumor of infancy is reported and the literature regarding this lesion is reviewed. The case reported shows the salient features of previously described melanotic neuroectodermal tumors of infancy; it occurs in infants of less than 1 year of age; it most commonly arises from bone (jaws and skull), has distinctive gross and histologic features, is benign, and is cured by total local excision. Since the teeth in the mandible and maxilla are undergoing development about the time that this tumor occurs, it is not surprising to find tooth buds in close proximity to the expanding neoplastic mass. When odontogenic rests are found in association with the lesion, it must be assumed that it is a collision of the two structures and not that the odontogenic epithelium is the origin for the lesion as previously thought. This is especially true since odontogenic epithelium is not found in the tumor when it occurs outside the jaws. This is the type of lesion that will most probably first be noticed by a dentist and should be managed by the oral surgeon. It is important to note that proper advice regarding future dental problems should be given to the parents of the infant. Such possibilities as crowding or absence of the deciduous or permanent teeth, malocclusion, and possible malformation of the remaining maxillary ridge should be explained. Close dental follow-up is mandatory since recurrence is possible."}
{"id": "PMID:187688", "title": "An immunocytochemical study of TSH beta storage in rat thyroidectomy cells with and without D or L thyroxine treatment.", "content": "Binding sites to the beta chain of thyroid stimulating hormone (TSH) were localized in pituitaries of thyroidectomized rats. Immunocytochemical staining was observed in hypertrophied TSH cells (\"thyroidectomy cells\") and primarily located in dilated rough endoplasmic reticulum. Staining was also found on the few secretory granules and on some of the intracisternal granules. Some of the thyroidectomy cells stained intensely, while others exhibited very little staining. When thyroidectomized rats were treated with thyroxine 4 days before death, the TSH cells contained more secretory granules, and the intracisternal granules were larger and more numerous. L-thyroxine was 10 times as potent as D-thyroxine in promoting the build-up of granules. Both types of granules stained intensely.", "contents": "An immunocytochemical study of TSH beta storage in rat thyroidectomy cells with and without D or L thyroxine treatment. Binding sites to the beta chain of thyroid stimulating hormone (TSH) were localized in pituitaries of thyroidectomized rats. Immunocytochemical staining was observed in hypertrophied TSH cells (\"thyroidectomy cells\") and primarily located in dilated rough endoplasmic reticulum. Staining was also found on the few secretory granules and on some of the intracisternal granules. Some of the thyroidectomy cells stained intensely, while others exhibited very little staining. When thyroidectomized rats were treated with thyroxine 4 days before death, the TSH cells contained more secretory granules, and the intracisternal granules were larger and more numerous. L-thyroxine was 10 times as potent as D-thyroxine in promoting the build-up of granules. Both types of granules stained intensely."}
{"id": "PMID:187689", "title": "A new histochemical method for the identification and visualization of both side chain acylated and nonacylated sialic acids.", "content": "A new histochemical method is described for the differentiation of mucins that utilizes two different Schiff reagents and allows single section identification of side chain O-acylated, and nonacylated, sialic acids in contrasting colors. In the event of mucins containing only one type of sialic acid, it may allow their specific identification (e.g., C7 or C8 side chain O-acylated). It has been shown to be useful in the identification of some metastases from adenocarcinomas of colon (where the primary is potassium hydroxide/periodic acid-Schiff positive) and should prove of great value in the investigation of diseases of the gastrointestinal tract and particularly those of the colon. It should also be valuable in the general field of epithelial mucin histochemistry, particularly for those mucins of the salivary and parotid glands, etc.", "contents": "A new histochemical method for the identification and visualization of both side chain acylated and nonacylated sialic acids. A new histochemical method is described for the differentiation of mucins that utilizes two different Schiff reagents and allows single section identification of side chain O-acylated, and nonacylated, sialic acids in contrasting colors. In the event of mucins containing only one type of sialic acid, it may allow their specific identification (e.g., C7 or C8 side chain O-acylated). It has been shown to be useful in the identification of some metastases from adenocarcinomas of colon (where the primary is potassium hydroxide/periodic acid-Schiff positive) and should prove of great value in the investigation of diseases of the gastrointestinal tract and particularly those of the colon. It should also be valuable in the general field of epithelial mucin histochemistry, particularly for those mucins of the salivary and parotid glands, etc."}
{"id": "PMID:187690", "title": "Lasar flow cytophotometric immunoperoxidase detection of herpes simplex virus type 2 antigens in infected cultured human cells.", "content": "Human cells in culture (HEp-2) were infected with herpes simplex virus type 2 (HSV-2) at multiplicities of infection varying from 0.2 to 10, and fixed 6, 12, 18 and 24 hr after infection. Infection-related antigens were detected by an indirect double antibody (peroxidase conjugated goat anti-rabbit to rabbit anti-herpes simplex virus type 2) immunoenzymatic staining reaction that rendered infection-related antigens visible by light microscopy. A corresponding series of laser flow cytophotometric experiments yielded reproducible large-angle (1-19 degrees) laser-light scattering distributions that depended upon multiplicities of infection and the location of the infection-related antigens in the infected cells.", "contents": "Lasar flow cytophotometric immunoperoxidase detection of herpes simplex virus type 2 antigens in infected cultured human cells. Human cells in culture (HEp-2) were infected with herpes simplex virus type 2 (HSV-2) at multiplicities of infection varying from 0.2 to 10, and fixed 6, 12, 18 and 24 hr after infection. Infection-related antigens were detected by an indirect double antibody (peroxidase conjugated goat anti-rabbit to rabbit anti-herpes simplex virus type 2) immunoenzymatic staining reaction that rendered infection-related antigens visible by light microscopy. A corresponding series of laser flow cytophotometric experiments yielded reproducible large-angle (1-19 degrees) laser-light scattering distributions that depended upon multiplicities of infection and the location of the infection-related antigens in the infected cells."}
{"id": "PMID:187691", "title": "Acrolein as a fixative for enzyme cytochemistry.", "content": "Since acrolein can penetrate more quickly and deeply into tissue blocks than glutaraldehyde, the possibility of the use of this aldehyde as a prefixative in enzyme cytochemistry was reinvestigated. At low concentrations, acrolein preserves the activities of the enzymes investigated, including those of glucose-6-phosphatase, which is known as one of the most vulnerable to aldehyde fixation; thus, acrolein is usable in enzyme ultracytochemistry. Enzyme activities are also preserved in tissues fixed with acrolein and glutaraldehyde combined. The rapid penetration of acrolein enables fixation in larger tissue blocks and provides greater freedom in specimen selection, especially important advantages when encountering heterogeneous materials as in pathology.", "contents": "Acrolein as a fixative for enzyme cytochemistry. Since acrolein can penetrate more quickly and deeply into tissue blocks than glutaraldehyde, the possibility of the use of this aldehyde as a prefixative in enzyme cytochemistry was reinvestigated. At low concentrations, acrolein preserves the activities of the enzymes investigated, including those of glucose-6-phosphatase, which is known as one of the most vulnerable to aldehyde fixation; thus, acrolein is usable in enzyme ultracytochemistry. Enzyme activities are also preserved in tissues fixed with acrolein and glutaraldehyde combined. The rapid penetration of acrolein enables fixation in larger tissue blocks and provides greater freedom in specimen selection, especially important advantages when encountering heterogeneous materials as in pathology."}
{"id": "PMID:187692", "title": "The effect of colostrum-derived antibody on louping-ill virus infection in lambs.", "content": "The influence of colostrum-derived antibody to louping-ill virus on the course of experimental infection was investigated in lambs. Lambs that had high titres of antibody were refractory to infection. Lambs that had low titres of antibody did not develop a viraemia but either showed an antibody reaction or were sensitized as judged by the immune response, which was typical of an anamnestic response, after rechallenge. Animals that had no antibody 34-20 days before challenge had either no or very slight viraemia, but did develop an antibody response with titres as high as those of control lambs by day 21. Lambs that had been negative for longer periods responded in a similar fashion to controls. These findings are discussed in relation to the occurrence of disease in lambs kept in louping-ill endemic areas. It is concluded that in such areas infections of lambs are likely to be of minor importance as a cause of mortality and of little epidemiological significance.", "contents": "The effect of colostrum-derived antibody on louping-ill virus infection in lambs. The influence of colostrum-derived antibody to louping-ill virus on the course of experimental infection was investigated in lambs. Lambs that had high titres of antibody were refractory to infection. Lambs that had low titres of antibody did not develop a viraemia but either showed an antibody reaction or were sensitized as judged by the immune response, which was typical of an anamnestic response, after rechallenge. Animals that had no antibody 34-20 days before challenge had either no or very slight viraemia, but did develop an antibody response with titres as high as those of control lambs by day 21. Lambs that had been negative for longer periods responded in a similar fashion to controls. These findings are discussed in relation to the occurrence of disease in lambs kept in louping-ill endemic areas. It is concluded that in such areas infections of lambs are likely to be of minor importance as a cause of mortality and of little epidemiological significance."}
{"id": "PMID:187693", "title": "Cell membrane antigen isolation with the staphylococcal protein A-antibody adsorbent.", "content": "Procedures are detailed for the rapid isolation of representative cell membrane antigens with protein A-bearing staphylococci as an adsorbent for IgG antibodies complexed with the antigens. Cell surface membrane proteins were radioiodinated and solubilized in nonionic detergent. Specific antisera were subsequently added and the immune complexes precipitated by addition of the staphylococcal adsorbent and low speed centrifugation. The antigens isolated included surface immunoglobulins from mouse and human lymphocytes, human beta-microglobulin and HL-A alloantigens, mouse H-2 alloantigens, and the murine leukemia virus glycoprotein gp 70. Rabbit, sheep, goat, and mouse antisera were all effective for the specific phase of the precipitation reaction. The surface membrane immunoglobulins of mouse splenic lymphocytes and human peripheral blood lymphocytes differed with respect to class composition and protein A reactivity. Mouse lymphocyte surface immunoglobulins were nonreactive with protein A, whereas a high proportion of human lymphocyte surface immunoglobulins of different classes bound directly to the staphylococci. In sequential immunoprecipitation studies the prior isolation of one antigen had no appreciable effect on the subsequent recovery of another antigen. Adsorption of antigen-antibody complexes is quantitative when protein A sites are provided in excess over antiserum IgG sites, and this obviates the need for equivalence point titrations for optimal precipitation necessary with alternative double antibody techniques.", "contents": "Cell membrane antigen isolation with the staphylococcal protein A-antibody adsorbent. Procedures are detailed for the rapid isolation of representative cell membrane antigens with protein A-bearing staphylococci as an adsorbent for IgG antibodies complexed with the antigens. Cell surface membrane proteins were radioiodinated and solubilized in nonionic detergent. Specific antisera were subsequently added and the immune complexes precipitated by addition of the staphylococcal adsorbent and low speed centrifugation. The antigens isolated included surface immunoglobulins from mouse and human lymphocytes, human beta-microglobulin and HL-A alloantigens, mouse H-2 alloantigens, and the murine leukemia virus glycoprotein gp 70. Rabbit, sheep, goat, and mouse antisera were all effective for the specific phase of the precipitation reaction. The surface membrane immunoglobulins of mouse splenic lymphocytes and human peripheral blood lymphocytes differed with respect to class composition and protein A reactivity. Mouse lymphocyte surface immunoglobulins were nonreactive with protein A, whereas a high proportion of human lymphocyte surface immunoglobulins of different classes bound directly to the staphylococci. In sequential immunoprecipitation studies the prior isolation of one antigen had no appreciable effect on the subsequent recovery of another antigen. Adsorption of antigen-antibody complexes is quantitative when protein A sites are provided in excess over antiserum IgG sites, and this obviates the need for equivalence point titrations for optimal precipitation necessary with alternative double antibody techniques."}
{"id": "PMID:187694", "title": "The involvement of cyclic nucleotide metabolism in the initiation of lymphocyte proliferation induced by mitogens.", "content": "Murine lymphocytes incubated with specific mitogens were examined for alterations in levels of intracellular cyclic AMP and cyclic GMP. Mitogenic concentrations of LPS elevate cyclic GMP levels; however, DxSO4, Poly I:C, PPD, Con A, and PHA show little immediate effect on cyclic GMP levels. Higher concentrations of all of these mitogens consistently elevate cyclic AMP levels. Exogenous cyclic GMP stimulates DNA synthesis in homozygous nude (nu/nu) spleen cultures but not in murine thymocyte cultures. Both LPS and cyclic GMP enhance the mitogenic response of thymocytes in the presence of suboptimal concentrations of Con A. Exogenous cyclic AMP inhibits mitogenic responses to both LPS and Con A; however, these inhibitory effects are partially reversed when cyclic GMP is also added to cultures. The mitogenic response of nu/nu spleen cells to LPS can be inhibited by high concentrations of Con A. This inhibition by Con A is also partially reversed by cyclic GMP, indicating that Con A may exert its effect by elevating intracellular levels of cyclic AMP. Thus, while lymphocytee mitogens may affect intracellular levels of both cyclic AMP and cyclic GMP, three effects show a consistent pattern. 1) Exogenous cyclic GMP is either mitogenic for B cells or agents that elevate cyclic GMP levels enhance the mitogenic response of T cells to Con A. 2) Increasing cyclic AMP levels inhibit cell proliferation induced by both B and T cell mitogens. 3) The inhibitory effects of cyclic AMP or cyclic AMP-elevating agents on mitogen-induced proliferation can be partially reversed by the presence of cyclic GMP. The opposing effects of these two cyclic nucleotides may reflect either their involvement in the initiation of cell proliferation or thei modulating effects on cell cycle events after the initiation process has been completed.", "contents": "The involvement of cyclic nucleotide metabolism in the initiation of lymphocyte proliferation induced by mitogens. Murine lymphocytes incubated with specific mitogens were examined for alterations in levels of intracellular cyclic AMP and cyclic GMP. Mitogenic concentrations of LPS elevate cyclic GMP levels; however, DxSO4, Poly I:C, PPD, Con A, and PHA show little immediate effect on cyclic GMP levels. Higher concentrations of all of these mitogens consistently elevate cyclic AMP levels. Exogenous cyclic GMP stimulates DNA synthesis in homozygous nude (nu/nu) spleen cultures but not in murine thymocyte cultures. Both LPS and cyclic GMP enhance the mitogenic response of thymocytes in the presence of suboptimal concentrations of Con A. Exogenous cyclic AMP inhibits mitogenic responses to both LPS and Con A; however, these inhibitory effects are partially reversed when cyclic GMP is also added to cultures. The mitogenic response of nu/nu spleen cells to LPS can be inhibited by high concentrations of Con A. This inhibition by Con A is also partially reversed by cyclic GMP, indicating that Con A may exert its effect by elevating intracellular levels of cyclic AMP. Thus, while lymphocytee mitogens may affect intracellular levels of both cyclic AMP and cyclic GMP, three effects show a consistent pattern. 1) Exogenous cyclic GMP is either mitogenic for B cells or agents that elevate cyclic GMP levels enhance the mitogenic response of T cells to Con A. 2) Increasing cyclic AMP levels inhibit cell proliferation induced by both B and T cell mitogens. 3) The inhibitory effects of cyclic AMP or cyclic AMP-elevating agents on mitogen-induced proliferation can be partially reversed by the presence of cyclic GMP. The opposing effects of these two cyclic nucleotides may reflect either their involvement in the initiation of cell proliferation or thei modulating effects on cell cycle events after the initiation process has been completed."}
{"id": "PMID:187695", "title": "Chemical treatment of macrophages increases their responsiveness to migration inhibitory factor (MIF).", "content": "The response of guinea pig macrophages to migration inhibitory factor (MIF) is altered by several chemical treatments. Treatment of macrophages with the diazonium salt of sulfanilic acid (5 x 10(-6) to 4 x 10(-4) M) significantly increases the response of these cells to MIF. Treatment with acetic anhydride also augments the response of these cells to MIF. The latter finding suggests that alteration of amino, hydroxyl, or sulfhydryl groups is involved in this phenomenon. Treatment of macrophages with sodium periodate (2 x 10(-5) to 10(-3) M) which is known to oxidize cis-glycols and with hydroxylamine (2 x 10(-5) to 2 x 10(-3) M), which reacts with carbonyl groups also increases response to MIF. The following experiments suggest that the significant alteration occurs at the level of the cell surface. Incubation of macrophages with the diazonium salt of sulfanilic acid at 4 degrees C, at which temperature pinocytosis is largely inhibited, is sufficient to increase the MIF response. The activity of the cytoplasmic enzyme aspartate aminotransferase, which in homogenates is susceptible to inactivation by low concentrations of the diazonium salt of sulfanilic acid, is not decreased when intact macrophages are incubated with high concentrations of the diazonium salt of sulfanilic acid. Cumulatively, these findings suggest that modification of different functional groups on the macrophage surface causes the same physiologic effect.", "contents": "Chemical treatment of macrophages increases their responsiveness to migration inhibitory factor (MIF). The response of guinea pig macrophages to migration inhibitory factor (MIF) is altered by several chemical treatments. Treatment of macrophages with the diazonium salt of sulfanilic acid (5 x 10(-6) to 4 x 10(-4) M) significantly increases the response of these cells to MIF. Treatment with acetic anhydride also augments the response of these cells to MIF. The latter finding suggests that alteration of amino, hydroxyl, or sulfhydryl groups is involved in this phenomenon. Treatment of macrophages with sodium periodate (2 x 10(-5) to 10(-3) M) which is known to oxidize cis-glycols and with hydroxylamine (2 x 10(-5) to 2 x 10(-3) M), which reacts with carbonyl groups also increases response to MIF. The following experiments suggest that the significant alteration occurs at the level of the cell surface. Incubation of macrophages with the diazonium salt of sulfanilic acid at 4 degrees C, at which temperature pinocytosis is largely inhibited, is sufficient to increase the MIF response. The activity of the cytoplasmic enzyme aspartate aminotransferase, which in homogenates is susceptible to inactivation by low concentrations of the diazonium salt of sulfanilic acid, is not decreased when intact macrophages are incubated with high concentrations of the diazonium salt of sulfanilic acid. Cumulatively, these findings suggest that modification of different functional groups on the macrophage surface causes the same physiologic effect."}
{"id": "PMID:187696", "title": "Immune interactions with cells infected with herpes simplex virus: antibodies to radioiodinated surface antigens.", "content": "Lactoperoxidase-catalyzed radioiodination was used to study reactions between surface antigens and antibodies on BHK-21 cells infected with HSV-1 and HSV-2. Isolation of iodinated surface antigens was achieved by indirect immune precipitation of Triton X-100 disrupted cells with antisera to HSV and IgG. Analysis of immune precipitates by polyacrylamide gel electrophoresis (PAGE) revealed at least 10 antigens, ranging in m.w. from 35 x 103 to 160 x 103 daltons. Antigens were detectable on cell surfaces as early as 2 hr post-infection. Electrophoretic patterns of surface antigens induced by HSV-1 were similar to those induced by HSV-2. In both cases the major portion of activity was associated with glycoprotein(s) in the range of 115 x 103 to 130 x 103 daltons. A reduced amount of radioactivity was obtained if cells were reacted with anti-HSV sera before disruption with Triton X-100, suggesting that less surface antigen was accessible to HSV antibody applied directly to intact cells.", "contents": "Immune interactions with cells infected with herpes simplex virus: antibodies to radioiodinated surface antigens. Lactoperoxidase-catalyzed radioiodination was used to study reactions between surface antigens and antibodies on BHK-21 cells infected with HSV-1 and HSV-2. Isolation of iodinated surface antigens was achieved by indirect immune precipitation of Triton X-100 disrupted cells with antisera to HSV and IgG. Analysis of immune precipitates by polyacrylamide gel electrophoresis (PAGE) revealed at least 10 antigens, ranging in m.w. from 35 x 103 to 160 x 103 daltons. Antigens were detectable on cell surfaces as early as 2 hr post-infection. Electrophoretic patterns of surface antigens induced by HSV-1 were similar to those induced by HSV-2. In both cases the major portion of activity was associated with glycoprotein(s) in the range of 115 x 103 to 130 x 103 daltons. A reduced amount of radioactivity was obtained if cells were reacted with anti-HSV sera before disruption with Triton X-100, suggesting that less surface antigen was accessible to HSV antibody applied directly to intact cells."}
{"id": "PMID:187697", "title": "Histamine modulation of eosinophil migration.", "content": "Preincubation of eosinophils with 10(-5) M or higher concentrations of histamine inhibited the eosinophil chemotactic response to endotoxin-activated serum whether by using the nucleopore filter assay and counting the cells migrating through the filter, or by using the Zigmond-Hirsch assay and counting the cells at each 10-mum interval. When the H2-receptor sites on the eosinophils were blocked by metiamide, the inhibitory capacity of histamine was prevented. Preincubation of eosinophils with 10(-6) M histamine increased the number of responding eosinophils to endotoxin-activated serum and this enhancement was blocked by an H1-receptor antagonist. Isoproteronol and aminophylline inhibited eosinophil movement and increasing concentrations of dibutryl cyclic AMP inhibited eosinophil migration. Concentrations of histamine that consistently resulted in inhibition of eosinophil movement stimulated an increase in cyclic AMP that was prevented by blocking the H2-receptor but not the H1-receptor. Thus, histamine-dependent inhibition of the eosinophil chemotactic response to other agents is mediated through the H2-receptor and is associated with an increase in the intracellular level of cyclic AMP whereas histamine dependent enhancement of eosinophil migration to other agents appears to be mediated through the H1-receptor. Eosinophils behave as a heterogeneous population as assessed by the ability of histamine to augment or inhibit cell migration. This may reflect differences in H1 to H2 receptor density or cell responsiveness to receptor stimulation. The chemoattractant activity of histamine itself is not influenced by H1 or H2 receptor antagonists, thus it is possible that an eosinophil has a third type of histamine receptor.", "contents": "Histamine modulation of eosinophil migration. Preincubation of eosinophils with 10(-5) M or higher concentrations of histamine inhibited the eosinophil chemotactic response to endotoxin-activated serum whether by using the nucleopore filter assay and counting the cells migrating through the filter, or by using the Zigmond-Hirsch assay and counting the cells at each 10-mum interval. When the H2-receptor sites on the eosinophils were blocked by metiamide, the inhibitory capacity of histamine was prevented. Preincubation of eosinophils with 10(-6) M histamine increased the number of responding eosinophils to endotoxin-activated serum and this enhancement was blocked by an H1-receptor antagonist. Isoproteronol and aminophylline inhibited eosinophil movement and increasing concentrations of dibutryl cyclic AMP inhibited eosinophil migration. Concentrations of histamine that consistently resulted in inhibition of eosinophil movement stimulated an increase in cyclic AMP that was prevented by blocking the H2-receptor but not the H1-receptor. Thus, histamine-dependent inhibition of the eosinophil chemotactic response to other agents is mediated through the H2-receptor and is associated with an increase in the intracellular level of cyclic AMP whereas histamine dependent enhancement of eosinophil migration to other agents appears to be mediated through the H1-receptor. Eosinophils behave as a heterogeneous population as assessed by the ability of histamine to augment or inhibit cell migration. This may reflect differences in H1 to H2 receptor density or cell responsiveness to receptor stimulation. The chemoattractant activity of histamine itself is not influenced by H1 or H2 receptor antagonists, thus it is possible that an eosinophil has a third type of histamine receptor."}
{"id": "PMID:187698", "title": "Reversal of SV40 tumor-mediated suppression of spleen cell cytotoxicity by antibody.", "content": "Spleen cells obtained from hamsters bearing PARA-7 tumors greater than 1.0 cm were not reactive in microcytotoxicity assays unless preincubated overnight. The events occurring during in vitro incubation which lead to reversal of tumor-mediated suppression of cellular immunity were investigated. After 24 hr of incubation, supernatants overlying spleen cells from tumor-bearing hosts contained a factor which blocked cytotoxicity of simian virus 40 (SV40)3-sensitized spleen cells at the PARA-7 target cell level but not at the effector cell level. The preparations did not mediate antibody-dependent cellular cytotoxicity (ADCC). Opposite results were obtained in assays of culture medium overlying spleen cells from hosts with a tumor burden less than 0.1 cm. Although ADCC activity was present, no significant blocking was detectable. Treatment of inactive spleen cells with anti-hamster gamma-globlin in the presence of complement (anti-HGG + C) prevented activation and formation of blocking factor but did not impair the cytotoxic activity of already activated cells. Addition of SV40 antiserum to anti-HGG + C-treated cells led to effector cell activation, whereas heterologous virus-immune sera did not. Control studies established that the antibody-mediated recovery of cytotoxicity was not due to arming. Further studies showed that PARA-7 tumor antigen extract blocked at the effector cell level, not at the target cell level. Addition of PARA-7 extract to spleen cell supernatants mediating ADCC resulted in formation of a factor which blocked at the target cell level but not at the effector cell level. These data are compatible with the following interpretation. Spleen cell unresponsiveness is due to antigen blockade. Recovery of cytotoxicity occurs because antibody synthesized during the incubation period promotes elution of antigen from the effector cell surface. Thus, activation is accompanied by the generation of tumor antigen-antibody complexes.", "contents": "Reversal of SV40 tumor-mediated suppression of spleen cell cytotoxicity by antibody. Spleen cells obtained from hamsters bearing PARA-7 tumors greater than 1.0 cm were not reactive in microcytotoxicity assays unless preincubated overnight. The events occurring during in vitro incubation which lead to reversal of tumor-mediated suppression of cellular immunity were investigated. After 24 hr of incubation, supernatants overlying spleen cells from tumor-bearing hosts contained a factor which blocked cytotoxicity of simian virus 40 (SV40)3-sensitized spleen cells at the PARA-7 target cell level but not at the effector cell level. The preparations did not mediate antibody-dependent cellular cytotoxicity (ADCC). Opposite results were obtained in assays of culture medium overlying spleen cells from hosts with a tumor burden less than 0.1 cm. Although ADCC activity was present, no significant blocking was detectable. Treatment of inactive spleen cells with anti-hamster gamma-globlin in the presence of complement (anti-HGG + C) prevented activation and formation of blocking factor but did not impair the cytotoxic activity of already activated cells. Addition of SV40 antiserum to anti-HGG + C-treated cells led to effector cell activation, whereas heterologous virus-immune sera did not. Control studies established that the antibody-mediated recovery of cytotoxicity was not due to arming. Further studies showed that PARA-7 tumor antigen extract blocked at the effector cell level, not at the target cell level. Addition of PARA-7 extract to spleen cell supernatants mediating ADCC resulted in formation of a factor which blocked at the target cell level but not at the effector cell level. These data are compatible with the following interpretation. Spleen cell unresponsiveness is due to antigen blockade. Recovery of cytotoxicity occurs because antibody synthesized during the incubation period promotes elution of antigen from the effector cell surface. Thus, activation is accompanied by the generation of tumor antigen-antibody complexes."}
{"id": "PMID:187699", "title": "Inhibition of the mitogenic response to lipopolysaccharide (LPS) in mouse spleen cells by polymyxin B.", "content": "The addition of low doses of the cationic polypeptide antibiotic, polymyxin B (PB), to cultures of mouse spleen cells inhibits lipopolysaccharide-(LPS) induced DNA synthesis but not that stimulated by PPD, PHA, or Con A. Inhibition is stoichiometric; the mitogenic response is suppressed by 50% at a weight ratio of PB:LPS of 0.055 to 1. Furthermore, PB-LPS complexes have a much reduced mitogenic capacity. These complexes inhibit the mitogenic response of spleen cells to unmodified LPS but not to PPD, Con A, or PHA. The inhibitory activity of PB is less effective when added after LPS is mixed with responding cells, achieving 50% inhibition when addition is made at 4 to 6 hr. Time course experiments indicate that partial inhibition is a reflection of a lower rate of DNA synthesis. Thus, PB inhibition of LPS mitogenesis apparently occurs as a result of formation of PB-LPS complexes with reduced mitogenic capacity. Specific inhibition by the complexes of mitogenesis induced by native LPS suggests that the inactive complex may bind to B cells but is unable to trigger them.", "contents": "Inhibition of the mitogenic response to lipopolysaccharide (LPS) in mouse spleen cells by polymyxin B. The addition of low doses of the cationic polypeptide antibiotic, polymyxin B (PB), to cultures of mouse spleen cells inhibits lipopolysaccharide-(LPS) induced DNA synthesis but not that stimulated by PPD, PHA, or Con A. Inhibition is stoichiometric; the mitogenic response is suppressed by 50% at a weight ratio of PB:LPS of 0.055 to 1. Furthermore, PB-LPS complexes have a much reduced mitogenic capacity. These complexes inhibit the mitogenic response of spleen cells to unmodified LPS but not to PPD, Con A, or PHA. The inhibitory activity of PB is less effective when added after LPS is mixed with responding cells, achieving 50% inhibition when addition is made at 4 to 6 hr. Time course experiments indicate that partial inhibition is a reflection of a lower rate of DNA synthesis. Thus, PB inhibition of LPS mitogenesis apparently occurs as a result of formation of PB-LPS complexes with reduced mitogenic capacity. Specific inhibition by the complexes of mitogenesis induced by native LPS suggests that the inactive complex may bind to B cells but is unable to trigger them."}
{"id": "PMID:187700", "title": "Immune response to acute otitis media in children III. Implications of viral antibody in middle ear fluid.", "content": "With the technique of radioimmunodiffusion and indirect FA staining, IgA antibody to measles, mumps, rubella, and polio-1 were determined in serum and middle ear fluid (MEF) of 103 patients with otitis media. The occurrence of IgA viral antibody in MEF and its absence in simultaneously drawn serum was used as an indicator of local antibody production. Of the 401 assays performed, 41 instances of IgA antibody exclusively in MEF were found. Only four of these occurred in specimens from unimmunized patients and were directed against rubella virus. Of the 37 remaining cases, 16 each were directed against measles and polio-1 and four and one, respectively, for mumps and rubella viruses. The mean specific IgA titers were from 8- to 17-fold higher in MEF from immunized individuals than in the unimmunized and persisted for at least 9 to 19 months after immunization. The data thus indicate 1) specific immunologic sensitization of the middle ear mucosa can be achieved by parenteral as well as oral routes of immunization, and 2) specific immunologic memory exists in the middle ear mucosa. These two factors are crucial to feasibility of immunization against acute otitis media.", "contents": "Immune response to acute otitis media in children III. Implications of viral antibody in middle ear fluid. With the technique of radioimmunodiffusion and indirect FA staining, IgA antibody to measles, mumps, rubella, and polio-1 were determined in serum and middle ear fluid (MEF) of 103 patients with otitis media. The occurrence of IgA viral antibody in MEF and its absence in simultaneously drawn serum was used as an indicator of local antibody production. Of the 401 assays performed, 41 instances of IgA antibody exclusively in MEF were found. Only four of these occurred in specimens from unimmunized patients and were directed against rubella virus. Of the 37 remaining cases, 16 each were directed against measles and polio-1 and four and one, respectively, for mumps and rubella viruses. The mean specific IgA titers were from 8- to 17-fold higher in MEF from immunized individuals than in the unimmunized and persisted for at least 9 to 19 months after immunization. The data thus indicate 1) specific immunologic sensitization of the middle ear mucosa can be achieved by parenteral as well as oral routes of immunization, and 2) specific immunologic memory exists in the middle ear mucosa. These two factors are crucial to feasibility of immunization against acute otitis media."}
{"id": "PMID:187701", "title": "Effect of selective complement deficiency on the rate of neutralization of enveloped viruses by human sera.", "content": "The capacity of human sera genetically deficient in selective complement (C) components to enhance neutralization of enveloped viruses was examined by kinetic plaque reduction assays. Vaccinia virus, a DNA virus, and vesicular stomatitis virus (VSV), an RNA virus, were studied. Exogenous rabbit: or human antibody to vaccinia virus, and guinea pig or human antibody to VSV were provided in limiting, C-dependent concentrations. IgG antibodies predominated in most of the antisera employed. C5-deficient and C6-deficient human sera consistently supported normal rates of neutralization of either virus; this effect was heat-labile. C4-deficient human serum did hot exceed heat-inactivated serum in any neutralization assay. C1r-deficient serum displayed slight heat-labile neutralizing capacity against vaccinia but none against VSV. C2- and C3-deficient sera consistently exhibited measurable but clearly subnormal rates of neutralization. Two fresh agammaglobulinemic sera failed to inactivate either virus in the absence of added antibody. These results confirm and extend earlier evidence, based on neutralization of herpes simplex and Newcastle disease viruses in the presence of early (IgM) antibody and functionally pure guinea pig C components or C-deficient animal sera, that the late-acting components C5-C9 are not required for C-dependent neutralization. Data on four enveloped viruses now agree that this function is mediated by C1-C3, although C1 plus C4 appear to have some neutralizing capacity. This requirement for C1-C3 is overcome, however, in the presence of higher antibody cohcentrations, suggesting that the contribution of the C system to viral neutralization in vivo may be chiefly in the early phase of infection when antibody is limited.", "contents": "Effect of selective complement deficiency on the rate of neutralization of enveloped viruses by human sera. The capacity of human sera genetically deficient in selective complement (C) components to enhance neutralization of enveloped viruses was examined by kinetic plaque reduction assays. Vaccinia virus, a DNA virus, and vesicular stomatitis virus (VSV), an RNA virus, were studied. Exogenous rabbit: or human antibody to vaccinia virus, and guinea pig or human antibody to VSV were provided in limiting, C-dependent concentrations. IgG antibodies predominated in most of the antisera employed. C5-deficient and C6-deficient human sera consistently supported normal rates of neutralization of either virus; this effect was heat-labile. C4-deficient human serum did hot exceed heat-inactivated serum in any neutralization assay. C1r-deficient serum displayed slight heat-labile neutralizing capacity against vaccinia but none against VSV. C2- and C3-deficient sera consistently exhibited measurable but clearly subnormal rates of neutralization. Two fresh agammaglobulinemic sera failed to inactivate either virus in the absence of added antibody. These results confirm and extend earlier evidence, based on neutralization of herpes simplex and Newcastle disease viruses in the presence of early (IgM) antibody and functionally pure guinea pig C components or C-deficient animal sera, that the late-acting components C5-C9 are not required for C-dependent neutralization. Data on four enveloped viruses now agree that this function is mediated by C1-C3, although C1 plus C4 appear to have some neutralizing capacity. This requirement for C1-C3 is overcome, however, in the presence of higher antibody cohcentrations, suggesting that the contribution of the C system to viral neutralization in vivo may be chiefly in the early phase of infection when antibody is limited."}
{"id": "PMID:187702", "title": "In vitro induction of cell-mediated immunity to murine leukemia cells. I. Optimization of tissue culture conditions for the generation of cytotoxic lymphocytes.", "content": "Cytotoxic lymphocytes (CTL) to allogeneic and syngeneic murine leukemia cells were generated in vitro in \"one way\" mixed lymphocyte-tumor cell cultures carried out under a variety of conditions. In an attempt to define the optimal culture conditions for sensitization, the following parameters were analyzed: culture vessel, culture volume, responder: stimulator (R:S) cell ratio, lymphoid cell density, source of lymphoid cells, duration of culture, fetal calf serum (FCS) concentration, 2-mercaptoethanol (2-ME) concentration, concentration of amino acids, and buffering system. Of the many variables examined, of particular importance were the R:S cell ratio, the cell density, the FCS concentration, the presence of 2-ME, and the time of harvesting. These factors exerted various effects, both quantitatively and qualitatively, on the magnitude and kinetics of the responses induced in microcultures (5 X 10(6) lymphocytes) and macrocultures (25 X 10(6) lymphocytes). Moreover, optimal sensitization in syngeneic cultures required different conditions than those for allogeneic cultures. Cytotoxic activity was assessed in vitro by a quantitative 51Cr-release assay. The sensitized lymphocytes demonstrated the characteristics ofT lymphocytes and reacted specifically with the sensitizing leukemia cells.", "contents": "In vitro induction of cell-mediated immunity to murine leukemia cells. I. Optimization of tissue culture conditions for the generation of cytotoxic lymphocytes. Cytotoxic lymphocytes (CTL) to allogeneic and syngeneic murine leukemia cells were generated in vitro in \"one way\" mixed lymphocyte-tumor cell cultures carried out under a variety of conditions. In an attempt to define the optimal culture conditions for sensitization, the following parameters were analyzed: culture vessel, culture volume, responder: stimulator (R:S) cell ratio, lymphoid cell density, source of lymphoid cells, duration of culture, fetal calf serum (FCS) concentration, 2-mercaptoethanol (2-ME) concentration, concentration of amino acids, and buffering system. Of the many variables examined, of particular importance were the R:S cell ratio, the cell density, the FCS concentration, the presence of 2-ME, and the time of harvesting. These factors exerted various effects, both quantitatively and qualitatively, on the magnitude and kinetics of the responses induced in microcultures (5 X 10(6) lymphocytes) and macrocultures (25 X 10(6) lymphocytes). Moreover, optimal sensitization in syngeneic cultures required different conditions than those for allogeneic cultures. Cytotoxic activity was assessed in vitro by a quantitative 51Cr-release assay. The sensitized lymphocytes demonstrated the characteristics ofT lymphocytes and reacted specifically with the sensitizing leukemia cells."}
{"id": "PMID:187706", "title": "The development of adrenocorticotrophin-sensitive adenylate cyclase activity in the foetal rabbit adrenal: a correlated biochemical and morphological study.", "content": "Proliferation of the smooth endoplasmic reticulum, the site of some hydroxylating steroidogenic enzymes in foetal adrenocortical cells, is the first major change in the process of their differentiation into steroidogenic tissue. This was observed in our ultrastructural studies on foetal rabbit adrenals to begin at about day 19 of development. Morphological changes in the mitochondria, the site of production of other steroidogenic enzymes, occurred at about day 24. The elongated or rod-shaped forms of the earlier stages became flattened and rounded by this time, while the cristae were transformed from a flattened lamellar type of the earlier stages to the tubulo-vesicular form of the adult. Other changes observed included an increase  in microvilli and in cell size, with a concomitant increase in thickness of the gland. Adenylate cyclase activity in foetal adrenal homogenates was assessed in response to sodium fluoride (NaF) and ACTH. All preparations responded to NaF. While good responses to ACTH were observed at days 24, 27, 28 and in the neonate, there was a lack of any significant response in the day 19 gland. Foetal ACTH was depressed by administration of cortisol, and the effects of this treatment on both the morphological changes and adenylate cyclase activity was reassessed. The response of foetal adrenals to ACTH was depressed by this treatment and differentiation of the mitochondria was arrested. These results suggest a circumscribed period for the development of ACTH-sensitive adenylate cyclase coinciding with the time at which final differentiation of the mitochondria is completed. Furthermore, both the differentiation of the mitochondria and the development of ACTH-sensitive adenylate cyclase in the foetal adrenal may be dependent on foetal ACTH secretion.", "contents": "The development of adrenocorticotrophin-sensitive adenylate cyclase activity in the foetal rabbit adrenal: a correlated biochemical and morphological study. Proliferation of the smooth endoplasmic reticulum, the site of some hydroxylating steroidogenic enzymes in foetal adrenocortical cells, is the first major change in the process of their differentiation into steroidogenic tissue. This was observed in our ultrastructural studies on foetal rabbit adrenals to begin at about day 19 of development. Morphological changes in the mitochondria, the site of production of other steroidogenic enzymes, occurred at about day 24. The elongated or rod-shaped forms of the earlier stages became flattened and rounded by this time, while the cristae were transformed from a flattened lamellar type of the earlier stages to the tubulo-vesicular form of the adult. Other changes observed included an increase  in microvilli and in cell size, with a concomitant increase in thickness of the gland. Adenylate cyclase activity in foetal adrenal homogenates was assessed in response to sodium fluoride (NaF) and ACTH. All preparations responded to NaF. While good responses to ACTH were observed at days 24, 27, 28 and in the neonate, there was a lack of any significant response in the day 19 gland. Foetal ACTH was depressed by administration of cortisol, and the effects of this treatment on both the morphological changes and adenylate cyclase activity was reassessed. The response of foetal adrenals to ACTH was depressed by this treatment and differentiation of the mitochondria was arrested. These results suggest a circumscribed period for the development of ACTH-sensitive adenylate cyclase coinciding with the time at which final differentiation of the mitochondria is completed. Furthermore, both the differentiation of the mitochondria and the development of ACTH-sensitive adenylate cyclase in the foetal adrenal may be dependent on foetal ACTH secretion."}
{"id": "PMID:187707", "title": "Effect of adrenergic blockade and dexamethasone on the aldosterone response to brain stimulation in the rhesus monkey.", "content": "The increase in aldosterone and plasma renin activity (PRA) observed after stimulation of extrahypothalamic sites within the brain of the rhesus monkey was prevented by the prior administration of the beta-adrenergic blocking agent propranolol. alpha-Adrenergic blockade by phentolamine had no inhibiting effect. Propranolol only partially reduced the response of aldosterone to lateral hypothalamic stimulation in spite of inhibition of PRA; a partial reduction in aldosterone was also obtained from this site after dexamethasone treatment without any effect on PRA. It was concluded that the increase in aldosterone observed after extra-hypothalamic stimulation was mediated mainly through the renin-angiotensin mechanism whereas in the case of the hypothalamus, release of ACTH was also a contributory factor.", "contents": "Effect of adrenergic blockade and dexamethasone on the aldosterone response to brain stimulation in the rhesus monkey. The increase in aldosterone and plasma renin activity (PRA) observed after stimulation of extrahypothalamic sites within the brain of the rhesus monkey was prevented by the prior administration of the beta-adrenergic blocking agent propranolol. alpha-Adrenergic blockade by phentolamine had no inhibiting effect. Propranolol only partially reduced the response of aldosterone to lateral hypothalamic stimulation in spite of inhibition of PRA; a partial reduction in aldosterone was also obtained from this site after dexamethasone treatment without any effect on PRA. It was concluded that the increase in aldosterone observed after extra-hypothalamic stimulation was mediated mainly through the renin-angiotensin mechanism whereas in the case of the hypothalamus, release of ACTH was also a contributory factor."}
{"id": "PMID:187709", "title": "Pregnant mare serum gonadotrophin: ratio of follicle-stimulating hormone and luteinizing hormone activities measured by radioreceptor assay.", "content": "Specific radioreceptor assays for FSH and LH, which employ tissue receptors from rat testis and highly purified human FSH (LER 1575-C) and LH (Hartree IRC-2, 24/6/69) as standards, have been developed to determine the FSH-like and LH-like activities in pregnant mare serum gonadotropin (PMSG). Measurements of FSH and LH concentrations in the serum of six pregnant Pony mares showed that the ratio of these two activities did not vary significantly between mares and remained constant between days 40 and 80 of gestation with a value of 1-45 +/- 0-04 (S.E.M.). The FSH:LH ratio of PMSG produced by cultured equine trophoblast cells was found to be 0-72 +/- 0-03 (S.E.M.) and that of partially purified serum extracts of PMSG 1-08 (range 0-87-1-30).", "contents": "Pregnant mare serum gonadotrophin: ratio of follicle-stimulating hormone and luteinizing hormone activities measured by radioreceptor assay. Specific radioreceptor assays for FSH and LH, which employ tissue receptors from rat testis and highly purified human FSH (LER 1575-C) and LH (Hartree IRC-2, 24/6/69) as standards, have been developed to determine the FSH-like and LH-like activities in pregnant mare serum gonadotropin (PMSG). Measurements of FSH and LH concentrations in the serum of six pregnant Pony mares showed that the ratio of these two activities did not vary significantly between mares and remained constant between days 40 and 80 of gestation with a value of 1-45 +/- 0-04 (S.E.M.). The FSH:LH ratio of PMSG produced by cultured equine trophoblast cells was found to be 0-72 +/- 0-03 (S.E.M.) and that of partially purified serum extracts of PMSG 1-08 (range 0-87-1-30)."}
{"id": "PMID:187710", "title": "The signal from fruiting body and conus tips of Dictyostelium discoideum.", "content": "Tips from fruiting bodies and conuses were transplanted into interphase fields of Dictyostelium discoideum amoebae. Progressively increasing concentrations of beef-heart phosphodiesterase added to the fields significantly decreased the chemotactic range of the responding amoebae. The findings suggest that the tip secretes c-AMP. We also find that the chemotactic range is independent of the size of the tip implying that the tip may produce a regulating gradient.", "contents": "The signal from fruiting body and conus tips of Dictyostelium discoideum. Tips from fruiting bodies and conuses were transplanted into interphase fields of Dictyostelium discoideum amoebae. Progressively increasing concentrations of beef-heart phosphodiesterase added to the fields significantly decreased the chemotactic range of the responding amoebae. The findings suggest that the tip secretes c-AMP. We also find that the chemotactic range is independent of the size of the tip implying that the tip may produce a regulating gradient."}
{"id": "PMID:187711", "title": "Cell aggregation and sexual differentiation in pairs of aggregation-deficient mutants of Dictyostelium discoideum.", "content": "A diffusible aggregation-stimulating factor (ASF) is released from a series of aggregation-deficient mutants. Biochemical markers indicate that these ASF-donor mutants are blocked at a later step of cell differentiation than an ASF-requiring mutant. ASF is able to bridge the initial block of differentiation in the latter mutant, such that development proceeds up to aggregation and even further. ASF is most probably neither identical with cyclic-AMP phosphodiesterase nor with an inhibitor of this enzyme which both are released from donor strains. In certain combinations of aggregation-deficient mutants, macrocysts, the sexual stages of Dictyostelium, are formed. Also, motile giant cells believed to be zygotes are observed in these mutant combinations. The gamone known to be released from one mating type and to induce macrocysts in the other, is probably not identical with ASF since this factor is produced by mutants derived from either one of both mating types.", "contents": "Cell aggregation and sexual differentiation in pairs of aggregation-deficient mutants of Dictyostelium discoideum. A diffusible aggregation-stimulating factor (ASF) is released from a series of aggregation-deficient mutants. Biochemical markers indicate that these ASF-donor mutants are blocked at a later step of cell differentiation than an ASF-requiring mutant. ASF is able to bridge the initial block of differentiation in the latter mutant, such that development proceeds up to aggregation and even further. ASF is most probably neither identical with cyclic-AMP phosphodiesterase nor with an inhibitor of this enzyme which both are released from donor strains. In certain combinations of aggregation-deficient mutants, macrocysts, the sexual stages of Dictyostelium, are formed. Also, motile giant cells believed to be zygotes are observed in these mutant combinations. The gamone known to be released from one mating type and to induce macrocysts in the other, is probably not identical with ASF since this factor is produced by mutants derived from either one of both mating types."}
{"id": "PMID:187712", "title": "The neuronal basis of a sensory analyser, the acridid movement detector system. II. response decrement, convergence, and the nature of the excitatory afferents to the fan-like dendrites of the LGMD.", "content": "No dendritic spikes occur in the input fan of the lobular giant movement detector (LGMD) neurone. The action potentials are initiated at the point of thickening of the axon, which therefore represents the site of convergence of the retinotopic projection in the MD system. Previous work has shown that the site of decrement in response to repetitive visual stimulation is distal to this point. No change in spiking threshold in the LGMD could be demonstrated, and decrement in the number of LGMD action potentials is completely explained by the observed decrement of EPSPs recorded in the LGMD input dendritic fan. Possible postsynaptic mechanisms which might affect EPSP amplitude are excluded experimentally or shown to be improbable. Latency measurements during electrical stimulation in the second chiasma (which produces a decrementing EPSP in the fan) indicate that the pathway from the chiasma afferents to the LGMD fan is probably monosynaptic. By exclusion, the site of decrement appears to be located at the presynaptic terminal of that synapse. Generalization of habituation of the response to ON and OFF stimuli is demonstrated, showing that the presynaptic neurone at the labile synapse is an ON/OFF unit. The greater part of the previously described sensitivity gradient on the retina, relative to the MD response, appears to be explicable by the geometry of the LGMD fan and of the retinotopic projection. We conclude that the LGMD is fed by a homogeneous population of ON/OFF units running in the second optic chiasma, which form labile synapses on the input fan.", "contents": "The neuronal basis of a sensory analyser, the acridid movement detector system. II. response decrement, convergence, and the nature of the excitatory afferents to the fan-like dendrites of the LGMD. No dendritic spikes occur in the input fan of the lobular giant movement detector (LGMD) neurone. The action potentials are initiated at the point of thickening of the axon, which therefore represents the site of convergence of the retinotopic projection in the MD system. Previous work has shown that the site of decrement in response to repetitive visual stimulation is distal to this point. No change in spiking threshold in the LGMD could be demonstrated, and decrement in the number of LGMD action potentials is completely explained by the observed decrement of EPSPs recorded in the LGMD input dendritic fan. Possible postsynaptic mechanisms which might affect EPSP amplitude are excluded experimentally or shown to be improbable. Latency measurements during electrical stimulation in the second chiasma (which produces a decrementing EPSP in the fan) indicate that the pathway from the chiasma afferents to the LGMD fan is probably monosynaptic. By exclusion, the site of decrement appears to be located at the presynaptic terminal of that synapse. Generalization of habituation of the response to ON and OFF stimuli is demonstrated, showing that the presynaptic neurone at the labile synapse is an ON/OFF unit. The greater part of the previously described sensitivity gradient on the retina, relative to the MD response, appears to be explicable by the geometry of the LGMD fan and of the retinotopic projection. We conclude that the LGMD is fed by a homogeneous population of ON/OFF units running in the second optic chiasma, which form labile synapses on the input fan."}
{"id": "PMID:187713", "title": "Properties of a symmetric pair of serotonin-containing neurones in the cerebral ganglia of Planorbis.", "content": "1. There is a bilaterally symmetric pair of large serotonin-containing neurones in the cerebral ganglia of Planorbis corneus. 2. In some animals these neurones are connected by a non-rectifying electrotonic synapse, and fire in synchrony even at prolonged high frequency. In other animals the neurones are not coupled, and fire independently except when driven by common input. Occasionally the coupling is weak. 3. Both coupled and non-coupled serotonin neurones have processes in the major nerve trunks of both buccal ganglia. 4. Synapses are made with many neurones in the buccal ganglia. The serotonin neurones can initiate firing in several motoneurones and thus produce movements of the buccal mass. 5. During spontaneous feeding cycles the input and firing pattern of the serotonin neurones do not bear any obvious relation to the movements of the buccal mass. 6. The data suggest that the serotonin neurones are modulatory cells, altering the level of excitability of buccal ganglion neurones.", "contents": "Properties of a symmetric pair of serotonin-containing neurones in the cerebral ganglia of Planorbis. 1. There is a bilaterally symmetric pair of large serotonin-containing neurones in the cerebral ganglia of Planorbis corneus. 2. In some animals these neurones are connected by a non-rectifying electrotonic synapse, and fire in synchrony even at prolonged high frequency. In other animals the neurones are not coupled, and fire independently except when driven by common input. Occasionally the coupling is weak. 3. Both coupled and non-coupled serotonin neurones have processes in the major nerve trunks of both buccal ganglia. 4. Synapses are made with many neurones in the buccal ganglia. The serotonin neurones can initiate firing in several motoneurones and thus produce movements of the buccal mass. 5. During spontaneous feeding cycles the input and firing pattern of the serotonin neurones do not bear any obvious relation to the movements of the buccal mass. 6. The data suggest that the serotonin neurones are modulatory cells, altering the level of excitability of buccal ganglion neurones."}
{"id": "PMID:187714", "title": "Identification of a cell-surface antigen selectively expressed on the natural killer cell.", "content": "We have studied the cell-surface phenotype of natural killer (NK) cells of NZB and B6 mice which react to an MuLV+ lymphoid tumor. (a) NK cells do not express Thy1, Ly2, or Ig surface markers. (b) NK cells express an antigen recognized by C3H anti-CE antiserum ('anti-Ly1.2 antiserum'). Inasmuch as NK activity of spleen cells from B6 and B6/Ly1.1 congenic strains were both equally sensitive to C3H anti-CE antiserum, the NK antigen is distinct from Ly1.2. This point was confirmed by the observation that alphaNK activity was removed by absorption of C3H anti-CE antiserum with spleen cells from either B6 or B6/Ly1.1 congenic strains. Absorption of C3H alphaCE serum with BALB/c thymocytes and spleen cells (which are Ly1.2+NK-) removed anti-Ly1.2 activity and left anti-NK activity intact. This absorption step could be circumvented by inserting the BALB/c genotype into the recipient immunized to CE cells (i.e., (C3H X BALB/c)F1 alphaCE spleen cells). This antiserum, provisionally termed 'anti-NK', defines a new subclass of lymphocytes which may play a central role in the immunosurveillance against tumors.", "contents": "Identification of a cell-surface antigen selectively expressed on the natural killer cell. We have studied the cell-surface phenotype of natural killer (NK) cells of NZB and B6 mice which react to an MuLV+ lymphoid tumor. (a) NK cells do not express Thy1, Ly2, or Ig surface markers. (b) NK cells express an antigen recognized by C3H anti-CE antiserum ('anti-Ly1.2 antiserum'). Inasmuch as NK activity of spleen cells from B6 and B6/Ly1.1 congenic strains were both equally sensitive to C3H anti-CE antiserum, the NK antigen is distinct from Ly1.2. This point was confirmed by the observation that alphaNK activity was removed by absorption of C3H anti-CE antiserum with spleen cells from either B6 or B6/Ly1.1 congenic strains. Absorption of C3H alphaCE serum with BALB/c thymocytes and spleen cells (which are Ly1.2+NK-) removed anti-Ly1.2 activity and left anti-NK activity intact. This absorption step could be circumvented by inserting the BALB/c genotype into the recipient immunized to CE cells (i.e., (C3H X BALB/c)F1 alphaCE spleen cells). This antiserum, provisionally termed 'anti-NK', defines a new subclass of lymphocytes which may play a central role in the immunosurveillance against tumors."}
{"id": "PMID:187715", "title": "The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. I. Proliferative response.", "content": "The lymphocytosis-promoting factor of Bordetella pertussis is a potent mitogen for murine lymphocytes in vitro. The stimulatory response was not the result of specific antigen stimulation. Spleen and lymph node cells were responsive, whereas normal thymocytes were unresponsive. However, DNA replication was induced in cortisone-resistant thymocytes by lymphocytosis-promoting factor (LPF). Bone marrow cells were not stimulated by LPF.", "contents": "The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. I. Proliferative response. The lymphocytosis-promoting factor of Bordetella pertussis is a potent mitogen for murine lymphocytes in vitro. The stimulatory response was not the result of specific antigen stimulation. Spleen and lymph node cells were responsive, whereas normal thymocytes were unresponsive. However, DNA replication was induced in cortisone-resistant thymocytes by lymphocytosis-promoting factor (LPF). Bone marrow cells were not stimulated by LPF."}
{"id": "PMID:187716", "title": "The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes: II. Nature of the responding cells.", "content": "The mitogenic response of murine lymphocytes to the lymphocytosis-promoting factor of Bordetella pertussis has been shown to be due to activation of T cells. The selectivity of responsiveness to LPF with respect to the population of T cells which is stimllated, differs from that of PHA as well as Con A, and the surface receptors are different. A population of adherent cells, which does not appear to consist of macrophages or other phagocytic cells, is required for the T-cell response.", "contents": "The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes: II. Nature of the responding cells. The mitogenic response of murine lymphocytes to the lymphocytosis-promoting factor of Bordetella pertussis has been shown to be due to activation of T cells. The selectivity of responsiveness to LPF with respect to the population of T cells which is stimllated, differs from that of PHA as well as Con A, and the surface receptors are different. A population of adherent cells, which does not appear to consist of macrophages or other phagocytic cells, is required for the T-cell response."}
{"id": "PMID:187717", "title": "Isolation of variants in phagocytosis of a macrophage-like continuous cell line.", "content": "We have isolated cloned variants in phagocytosis from a cloned continuous murine macrophage-like cell line, J 774.2. A selection procedure against Fc receptor-mediated phagocytosis was devised using IgG-coated SRBC containing a toxic drug, tubercidin, as the lethal agent. A series of variant clones deficient in Fc receptor-mediated phagocytosis were isolated. Such variants occurred at low frequency (approximately 6 X 10(-5)), were stable, and appeared to possess Fc receptors. The degree to which they were defective in phagocytosis of IgG-coated SRBC varied from clone to clone, yet all clones, were able to phagocytize latex particles. The phagocytic defect in some variants could be corrected by the addition of 8 Br-cAMP, in others, the drug was without effect. It is likely, therefore, that different variants are defective in several distinct steps critical to Fc receptor-mediated phagocytosis.", "contents": "Isolation of variants in phagocytosis of a macrophage-like continuous cell line. We have isolated cloned variants in phagocytosis from a cloned continuous murine macrophage-like cell line, J 774.2. A selection procedure against Fc receptor-mediated phagocytosis was devised using IgG-coated SRBC containing a toxic drug, tubercidin, as the lethal agent. A series of variant clones deficient in Fc receptor-mediated phagocytosis were isolated. Such variants occurred at low frequency (approximately 6 X 10(-5)), were stable, and appeared to possess Fc receptors. The degree to which they were defective in phagocytosis of IgG-coated SRBC varied from clone to clone, yet all clones, were able to phagocytize latex particles. The phagocytic defect in some variants could be corrected by the addition of 8 Br-cAMP, in others, the drug was without effect. It is likely, therefore, that different variants are defective in several distinct steps critical to Fc receptor-mediated phagocytosis."}
{"id": "PMID:187718", "title": "Hypercalcemia.", "content": "Hypercalcemia is a potentially life-threatening metabolic disorder which may be effectively treated once its presence is recognized and its probable cause determined. The family physician should be aware of the various clinical circumstances in which hypercalcemia occurs and the appropriate initial therapy for patients who are symptomatic at the time of diagnosis. This paper provides a clear approach to the pathogenesis, diagnosis, and management of this problem.", "contents": "Hypercalcemia. Hypercalcemia is a potentially life-threatening metabolic disorder which may be effectively treated once its presence is recognized and its probable cause determined. The family physician should be aware of the various clinical circumstances in which hypercalcemia occurs and the appropriate initial therapy for patients who are symptomatic at the time of diagnosis. This paper provides a clear approach to the pathogenesis, diagnosis, and management of this problem."}
{"id": "PMID:187719", "title": "Enhanced resistance of mice to infection with Langat (TP21) virus following pre-treatment with Sindbis or Semliki forest virus.", "content": "Significant protection to heterologous i.c. challenge with the flavovirus Langat occurred after a single i.c. injection of avirulent strains of the alpha viruses Semliki Forest or Sindbis given 1 day to 5 weeks before challenge. Some protection also occurred after an i.p. infection with these viruses. We consider that the protection afforded by the alpha viruses is due to interference with the multiplication of Langat virus and is related to the maximum level of brain infectivity reached in the alpha virus infection.", "contents": "Enhanced resistance of mice to infection with Langat (TP21) virus following pre-treatment with Sindbis or Semliki forest virus. Significant protection to heterologous i.c. challenge with the flavovirus Langat occurred after a single i.c. injection of avirulent strains of the alpha viruses Semliki Forest or Sindbis given 1 day to 5 weeks before challenge. Some protection also occurred after an i.p. infection with these viruses. We consider that the protection afforded by the alpha viruses is due to interference with the multiplication of Langat virus and is related to the maximum level of brain infectivity reached in the alpha virus infection."}
{"id": "PMID:187720", "title": "Changes in transcription of endogenous type-C virus genome during mouse liver regeneration.", "content": "In the present study the extent of endogenous, type-C virus genome transcription in normal and regenerating mouse liver was analysed by using the technique of nucleic acid hybridization. The RNA preparations from regenerating liver tissues collected at various intervals following partial hepatectomy, and from normal liver samples of BALB/c mice, were hybridized to 3H-DNA complementary to 60 to 70S RNA of an endogenous, N-tropic virus, released spontaneously from BALB/c mouse cells in culture. Although partial transcription of the endogenous virus genome can be clearly detected in normal liver, a significant increase in the level of virus-specific RNA synthesis in the regenerating liver, in comparison to normal liver, is apparent, following partial hepatectomy. This increase in virus-specific RNA synthesis attains its highest level just before the level of DNA synthesis in the regenerating liver reaches its maximum. These observations may indicate a qualitative or quantitative change in the endogenous type-C virus genome transcription pattern in hepatocytes, in response to partial hepatectomy and suggest that this change in the transcription pattern and the initiation of cell proliferation, in regenerating livers, are probably sequential and related events.", "contents": "Changes in transcription of endogenous type-C virus genome during mouse liver regeneration. In the present study the extent of endogenous, type-C virus genome transcription in normal and regenerating mouse liver was analysed by using the technique of nucleic acid hybridization. The RNA preparations from regenerating liver tissues collected at various intervals following partial hepatectomy, and from normal liver samples of BALB/c mice, were hybridized to 3H-DNA complementary to 60 to 70S RNA of an endogenous, N-tropic virus, released spontaneously from BALB/c mouse cells in culture. Although partial transcription of the endogenous virus genome can be clearly detected in normal liver, a significant increase in the level of virus-specific RNA synthesis in the regenerating liver, in comparison to normal liver, is apparent, following partial hepatectomy. This increase in virus-specific RNA synthesis attains its highest level just before the level of DNA synthesis in the regenerating liver reaches its maximum. These observations may indicate a qualitative or quantitative change in the endogenous type-C virus genome transcription pattern in hepatocytes, in response to partial hepatectomy and suggest that this change in the transcription pattern and the initiation of cell proliferation, in regenerating livers, are probably sequential and related events."}
{"id": "PMID:187721", "title": "An improved technique for obtaining enhanced infectivity with herpes simplex virus type 1 DNA.", "content": "Cells infected with herpes simplex virus type 1 (HSV-1) DNA by the calcium phosphate precipitation technique produce virus which leads to the formation of plaques (Graham, Veldhuisen & Wilkie, 1973). In the study reported here we show that treatment of cell monolayers with dimethyl sulphoxide (DMSO) solutions after infection with DNA-calcium phosphate complexes leads to a considerable increase in the number of plaques obtained. The conditions for this enhancement of infectivity have been optimized for baby hamster kidney (BHK) cells, and increases in plaque numbers of over 100-fold have been obtained. The treatment appears to increase the proportion of cells which respond to DNA infection by initiating plaque formation, and results in a large increase in the measured specific infectivity of HSV-1 DNA. DMSO causes similar (but quantitatively different) responses in various other cell lines infected with HSV-1 DNA. BHK cells infected with either virus particles, or virus DNA by the DEAE-dextran technique (Laithier & Sheldrick, 1975), do not exhibit this massive enhancement following exposure to DMSO.", "contents": "An improved technique for obtaining enhanced infectivity with herpes simplex virus type 1 DNA. Cells infected with herpes simplex virus type 1 (HSV-1) DNA by the calcium phosphate precipitation technique produce virus which leads to the formation of plaques (Graham, Veldhuisen & Wilkie, 1973). In the study reported here we show that treatment of cell monolayers with dimethyl sulphoxide (DMSO) solutions after infection with DNA-calcium phosphate complexes leads to a considerable increase in the number of plaques obtained. The conditions for this enhancement of infectivity have been optimized for baby hamster kidney (BHK) cells, and increases in plaque numbers of over 100-fold have been obtained. The treatment appears to increase the proportion of cells which respond to DNA infection by initiating plaque formation, and results in a large increase in the measured specific infectivity of HSV-1 DNA. DMSO causes similar (but quantitatively different) responses in various other cell lines infected with HSV-1 DNA. BHK cells infected with either virus particles, or virus DNA by the DEAE-dextran technique (Laithier & Sheldrick, 1975), do not exhibit this massive enhancement following exposure to DMSO."}
{"id": "PMID:187722", "title": "The effects of herpes simplex virus type 1 on cellular DNA-dependent RNA polymerase activities.", "content": "An investigation of the activity of nuclear RNA polymerase following infection of LS cells with HSV-1 shows a decline in both major activities. This effect is not entirely due to inhibition of cellular protein synthesis, and the effect of alpha-amanitin-sensitive RNA polymerase is mediated by a protein(s) synthesized in the infected cell. Changes in the properties of this RNA polymerase activity include a reduction in the relative UTP/GTP incorporation ratio and an increased sensitivity to inhibition by actinomycin D, indicating that RNA polymerase II is involved in virus transcription.", "contents": "The effects of herpes simplex virus type 1 on cellular DNA-dependent RNA polymerase activities. An investigation of the activity of nuclear RNA polymerase following infection of LS cells with HSV-1 shows a decline in both major activities. This effect is not entirely due to inhibition of cellular protein synthesis, and the effect of alpha-amanitin-sensitive RNA polymerase is mediated by a protein(s) synthesized in the infected cell. Changes in the properties of this RNA polymerase activity include a reduction in the relative UTP/GTP incorporation ratio and an increased sensitivity to inhibition by actinomycin D, indicating that RNA polymerase II is involved in virus transcription."}
{"id": "PMID:187723", "title": "Polyadenylated virus-specific RNA in baby hamster kidney cells, transformed by polyoma virus.", "content": "RNA from a clone of polyoma virus-transformed hamster cells was fractionated by chromatography on oligo(dT)-cellulose. The proportion of virus-specific RNA in the polyadenylated and non-polyadenylated fractions was determined by hybridization of the labelled RNA with excess purified polyoma DNA, immobilized on filters. Seventy to 80% of the virus-specific RNA in both polysomal and total cell RNA was found in the polyadenylated fraction. Since it has been shown previously that more than 65% of the total virus-specific RNA is restricted to the nucleus in this cell line, these results indicate that a high proportion (at least 53%) of the nuclear virus-specific RNA is polyadenylated. The sedimentation profile of total polyadenylated virus-specific RNA in dimethyl sulphoxide was comprised mainly of a broad band with a median sedimentation coefficient about 26S (relative to 28S rRNA). This profile was similar to that of total nuclear, and not cytoplasmic, virus-specific RNA. To estimate the intramolecular proximity of virus-specific sequences to poly(A), total RNA was subjected to limited thermal scission to an average mol. wt. similar to that of mRNA. The RNA remaining attached to poly(A) was then isolated, using oligo(dT)-cellulose. It was found that 65% of the virus-specific RNA that was originally attached to poly(A) was released by the thermal scission. Most of the virus-specific sequence within polyadenylated RNA molecules therefore must have been located at some distance from the polyadenylated 3'-terminus. This observation, together with the results of sedimentation analysis, can most simply be explained by postulating the existence of 'hybrid' RNA molecules containing a host-specified sequence located between a virus-specific sequence and the 3'-terminal poly(A).", "contents": "Polyadenylated virus-specific RNA in baby hamster kidney cells, transformed by polyoma virus. RNA from a clone of polyoma virus-transformed hamster cells was fractionated by chromatography on oligo(dT)-cellulose. The proportion of virus-specific RNA in the polyadenylated and non-polyadenylated fractions was determined by hybridization of the labelled RNA with excess purified polyoma DNA, immobilized on filters. Seventy to 80% of the virus-specific RNA in both polysomal and total cell RNA was found in the polyadenylated fraction. Since it has been shown previously that more than 65% of the total virus-specific RNA is restricted to the nucleus in this cell line, these results indicate that a high proportion (at least 53%) of the nuclear virus-specific RNA is polyadenylated. The sedimentation profile of total polyadenylated virus-specific RNA in dimethyl sulphoxide was comprised mainly of a broad band with a median sedimentation coefficient about 26S (relative to 28S rRNA). This profile was similar to that of total nuclear, and not cytoplasmic, virus-specific RNA. To estimate the intramolecular proximity of virus-specific sequences to poly(A), total RNA was subjected to limited thermal scission to an average mol. wt. similar to that of mRNA. The RNA remaining attached to poly(A) was then isolated, using oligo(dT)-cellulose. It was found that 65% of the virus-specific RNA that was originally attached to poly(A) was released by the thermal scission. Most of the virus-specific sequence within polyadenylated RNA molecules therefore must have been located at some distance from the polyadenylated 3'-terminus. This observation, together with the results of sedimentation analysis, can most simply be explained by postulating the existence of 'hybrid' RNA molecules containing a host-specified sequence located between a virus-specific sequence and the 3'-terminal poly(A)."}
{"id": "PMID:187724", "title": "The location of the ploy(C) tract in the RNA of foot-and-mouth disease virus.", "content": "Fragments of foot-and-mouth disease virus RNA of decreasing size, containing the 3' poly(A) sequence have been prepared by alkali treatment and sucrose gradient centrifugation followed by oligo(dT)-cellulose affinity chromatography. Polyacrylamide gel electrophoresis of the ribonuclease T1 resistant oligonucleotides from these polyadenylated fragments has enabled us to locate the position of some of the longer oligonucleotides on the RNA. In particular the poly C tract has been shown to be near the 5' end of the RNA; The possible function of the poly(C) tract is discussed in the light of these findings.", "contents": "The location of the ploy(C) tract in the RNA of foot-and-mouth disease virus. Fragments of foot-and-mouth disease virus RNA of decreasing size, containing the 3' poly(A) sequence have been prepared by alkali treatment and sucrose gradient centrifugation followed by oligo(dT)-cellulose affinity chromatography. Polyacrylamide gel electrophoresis of the ribonuclease T1 resistant oligonucleotides from these polyadenylated fragments has enabled us to locate the position of some of the longer oligonucleotides on the RNA. In particular the poly C tract has been shown to be near the 5' end of the RNA; The possible function of the poly(C) tract is discussed in the light of these findings."}
{"id": "PMID:187725", "title": "An antigenically atypical strain of variola virus.", "content": "The Kuwait-5-67 strain of variola virus, although indistinguishable from variola virus in its other properties, behaved atypically in immuno-diffusion tests with antivaccinia serum. The precipitation line pattern produced was similar to that of cowpox virus but lacked one of the main precipitation bands given by all other strains of variola, alastrim and vaccinia viruses tested. Trypsin treatment of cowpox virus preparations revealed the missing precipitation line but did not do so with the Kuwait-5-67 strain. The antivaccinia serum absorbed by Kuwait-5-67 strain lost its ability to interact with this strain, but still gave precipitation lines with variola, vaccinia and cowpox viruses.", "contents": "An antigenically atypical strain of variola virus. The Kuwait-5-67 strain of variola virus, although indistinguishable from variola virus in its other properties, behaved atypically in immuno-diffusion tests with antivaccinia serum. The precipitation line pattern produced was similar to that of cowpox virus but lacked one of the main precipitation bands given by all other strains of variola, alastrim and vaccinia viruses tested. Trypsin treatment of cowpox virus preparations revealed the missing precipitation line but did not do so with the Kuwait-5-67 strain. The antivaccinia serum absorbed by Kuwait-5-67 strain lost its ability to interact with this strain, but still gave precipitation lines with variola, vaccinia and cowpox viruses."}
{"id": "PMID:187726", "title": "Comparison of the activities in inhibition of haemagglutination by different togaviruses for human serum lipoproteins and their constituents.", "content": "The 3 major lipoprotein fractions of human serum were investigated for their ability to inhibit the haemagglutination of 24 different togaviruses including rubella virus and arboviruses from 5 antigenic groups. All viruses were inhibited by the 3 fractions and this was most evident with low and very low density lipoproteins; inhibitory activity appeared to be associated with the lipid part of the lipoproteins. When artificial dispersions of the lipids cholesterol, cholesteryl ester and triglyceride were emulsified with egg lecithin three categories of inhibitory activity were observed which were independent of virus antigenic grouping -- category 1, no activity; category 2, activity confined to cholesterol and category 3, activity for cholesterol and to a lesser extent the other lipids.", "contents": "Comparison of the activities in inhibition of haemagglutination by different togaviruses for human serum lipoproteins and their constituents. The 3 major lipoprotein fractions of human serum were investigated for their ability to inhibit the haemagglutination of 24 different togaviruses including rubella virus and arboviruses from 5 antigenic groups. All viruses were inhibited by the 3 fractions and this was most evident with low and very low density lipoproteins; inhibitory activity appeared to be associated with the lipid part of the lipoproteins. When artificial dispersions of the lipids cholesterol, cholesteryl ester and triglyceride were emulsified with egg lecithin three categories of inhibitory activity were observed which were independent of virus antigenic grouping -- category 1, no activity; category 2, activity confined to cholesterol and category 3, activity for cholesterol and to a lesser extent the other lipids."}
{"id": "PMID:187727", "title": "Amino acid composition of the poliovirus capsid polypeptides isolated as fluorescamine conjugates.", "content": "Poliovirus was treated with fluorescamine and disrupted with sodium dodecyl sulphate (SDS). The polypeptides were isolated by electrophoresis in a polyacrylamide gel (SDS-PAGE) and their amino acid compositions determined. The compositions of VP1, 2 and 3 were very similar but different from that of VP4.", "contents": "Amino acid composition of the poliovirus capsid polypeptides isolated as fluorescamine conjugates. Poliovirus was treated with fluorescamine and disrupted with sodium dodecyl sulphate (SDS). The polypeptides were isolated by electrophoresis in a polyacrylamide gel (SDS-PAGE) and their amino acid compositions determined. The compositions of VP1, 2 and 3 were very similar but different from that of VP4."}
{"id": "PMID:187728", "title": "Isolation of the matrix (membrane) protein of vesicular stomatitis virus by gel filtration in guanidine hydrochloride.", "content": "The L, N and M proteins of vesicular stomatitis virus (VSV) were resolved from each other by gel filtration in the presence of 6 m-guanidine hydrochloride. Amino acid analysis for purified M protein of VSV showed that its chemical composition differed from those of influenza and SV5 M proteins.", "contents": "Isolation of the matrix (membrane) protein of vesicular stomatitis virus by gel filtration in guanidine hydrochloride. The L, N and M proteins of vesicular stomatitis virus (VSV) were resolved from each other by gel filtration in the presence of 6 m-guanidine hydrochloride. Amino acid analysis for purified M protein of VSV showed that its chemical composition differed from those of influenza and SV5 M proteins."}
{"id": "PMID:187729", "title": "Reactivation of herpes simplex virus infection by ultraviolet light and possible involvement of prostaglandins.", "content": "Herpes simplex infection in the mouse ear was used to investigate whether various treatments would reactivate the disease. Immunosuppressive drugs failed to induce clinical signs of reactivation but irradiation of the skin of the originally infected ear with ultraviolet light or injection of prostaglandin E2 or PBSA into this site, caused reactivation of infection. This was detected by the appearance of infectious virus in the skin 2 to 3 days after these treatments. The results are discussed in relation to the mechanism of herpes reactivation in man.", "contents": "Reactivation of herpes simplex virus infection by ultraviolet light and possible involvement of prostaglandins. Herpes simplex infection in the mouse ear was used to investigate whether various treatments would reactivate the disease. Immunosuppressive drugs failed to induce clinical signs of reactivation but irradiation of the skin of the originally infected ear with ultraviolet light or injection of prostaglandin E2 or PBSA into this site, caused reactivation of infection. This was detected by the appearance of infectious virus in the skin 2 to 3 days after these treatments. The results are discussed in relation to the mechanism of herpes reactivation in man."}
{"id": "PMID:187730", "title": "[Quantitative study of alpha-1-antitrypsin in an ethnic group of Ivory Coast: the Abrons].", "content": "A logarithmic-normal distribution of the concentrations of alpha1AT in 578 Abrons in Ivory Coast was found. A significant, negative logarithmic regression of alpha1AT rates according to age is demonstrated. alpha1AT rate = 0,376 (log age) + 3,003 The quantitative analysis by immunoprecipitation of Technicon only does not permit a definitive conclusion as to the presence of allele Z.", "contents": "[Quantitative study of alpha-1-antitrypsin in an ethnic group of Ivory Coast: the Abrons]. A logarithmic-normal distribution of the concentrations of alpha1AT in 578 Abrons in Ivory Coast was found. A significant, negative logarithmic regression of alpha1AT rates according to age is demonstrated. alpha1AT rate = 0,376 (log age) + 3,003 The quantitative analysis by immunoprecipitation of Technicon only does not permit a definitive conclusion as to the presence of allele Z."}
{"id": "PMID:187731", "title": "Visual pathways, acuity dominance, and visual half-field asymmetry.", "content": "The effects of the visual pathways and acuity dominance on visual half-field (VHF) recall of verbal stimuli were investigated with 36 right-handed male undergraduates, with the use of the Hines-Satz short-term memory paradigm under monocular conditions. Scores for stimuli transmitted via the left temporal and right nasal pathways were significantly greater than those for stimuli transmitted via the left nasal and right temporal pathways. No other significant differences were found for either the pathways or acuity dominance variables. The results were hypothesized to reflect the primary influence of hemispheric asymmetry of function on the VHF recall task.", "contents": "Visual pathways, acuity dominance, and visual half-field asymmetry. The effects of the visual pathways and acuity dominance on visual half-field (VHF) recall of verbal stimuli were investigated with 36 right-handed male undergraduates, with the use of the Hines-Satz short-term memory paradigm under monocular conditions. Scores for stimuli transmitted via the left temporal and right nasal pathways were significantly greater than those for stimuli transmitted via the left nasal and right temporal pathways. No other significant differences were found for either the pathways or acuity dominance variables. The results were hypothesized to reflect the primary influence of hemispheric asymmetry of function on the VHF recall task."}
{"id": "PMID:187735", "title": "Spinal evoked responses recorded from the epidural space in normal and diseased humans.", "content": "In 22 subjects, including normal subjects and patients with radicular or spinal cord lesions, the authors studied the spinal evoked responses recorded extradurally after stimulating mixed limb nerves. The responses obtained are discussed with particular reference to the clinical value of the changes in amplitude and latency of the spinal evoked potential with particular lesions.", "contents": "Spinal evoked responses recorded from the epidural space in normal and diseased humans. In 22 subjects, including normal subjects and patients with radicular or spinal cord lesions, the authors studied the spinal evoked responses recorded extradurally after stimulating mixed limb nerves. The responses obtained are discussed with particular reference to the clinical value of the changes in amplitude and latency of the spinal evoked potential with particular lesions."}
{"id": "PMID:187736", "title": "Carnitine-palmityl-transferase deficiency.", "content": "An increasing number of cases of myopathy due to disordered lipid metabolism have recently been recognised and these appear to fall into two contrasting clinical and biochemical categories. Some patients present with steadily prograssive proximal weakness which sometimes responds to steroid therapy and which is due to carnitine deficiency in skeletal muscle. In the second category, patients usually present with muscle cramps on exertion then followed by myoglobinuria without established proximal myopathy and their symptoms are associated with deficiency of carnitine palmityl transferase in skeletal muscle. In this paper we report a patient who has well-documented carnitine palmityl transferase deficiency, whose symptoms were triggered by violent exercise after fasting and in whom there was variable histochemical and ultrastructural evidence of lipid accumulation in muscle biopsy samples. Development of the patient's symptoms was suppressed by a high carbohydrate diet.", "contents": "Carnitine-palmityl-transferase deficiency. An increasing number of cases of myopathy due to disordered lipid metabolism have recently been recognised and these appear to fall into two contrasting clinical and biochemical categories. Some patients present with steadily prograssive proximal weakness which sometimes responds to steroid therapy and which is due to carnitine deficiency in skeletal muscle. In the second category, patients usually present with muscle cramps on exertion then followed by myoglobinuria without established proximal myopathy and their symptoms are associated with deficiency of carnitine palmityl transferase in skeletal muscle. In this paper we report a patient who has well-documented carnitine palmityl transferase deficiency, whose symptoms were triggered by violent exercise after fasting and in whom there was variable histochemical and ultrastructural evidence of lipid accumulation in muscle biopsy samples. Development of the patient's symptoms was suppressed by a high carbohydrate diet."}
{"id": "PMID:187737", "title": "[Multiple systemic atrophies, mental retardation, neurogenic amyotrophy and congenital bone fragility. A new neuro-generative disorder].", "content": "Five cases of a congenital neurological disorder are reported. Four patients, born after a breech delivery, belong to one sibship while the fifth patient is the only child in another family. The clinical features include quadriplegia, amyotrophy, a peripheral neuropathy, severe mental retardation and a subluxation of the hips. X-rays reveal diffuse osteoporosis and multiple spontaneous fractures. Autopsies in 3 patients showed multiple system atrophies involving the spinal cord and the cerebellum, coarse cerebral gyri and a marked reduction in volume of the white matter. These various pathological features are compared with the lesions found in a few other cases reported in the literature, none of which can be considered to be identical to the ones described. It is therefore felt that the condition under discussion represents a new syndrome to be classified, at least temporarily, within the group of multiple system atrophies.", "contents": "[Multiple systemic atrophies, mental retardation, neurogenic amyotrophy and congenital bone fragility. A new neuro-generative disorder]. Five cases of a congenital neurological disorder are reported. Four patients, born after a breech delivery, belong to one sibship while the fifth patient is the only child in another family. The clinical features include quadriplegia, amyotrophy, a peripheral neuropathy, severe mental retardation and a subluxation of the hips. X-rays reveal diffuse osteoporosis and multiple spontaneous fractures. Autopsies in 3 patients showed multiple system atrophies involving the spinal cord and the cerebellum, coarse cerebral gyri and a marked reduction in volume of the white matter. These various pathological features are compared with the lesions found in a few other cases reported in the literature, none of which can be considered to be identical to the ones described. It is therefore felt that the condition under discussion represents a new syndrome to be classified, at least temporarily, within the group of multiple system atrophies."}
{"id": "PMID:187738", "title": "Fatal systemic carnitine deficiency with lipid storage in skeletal muscle, heart, liver and kidney.", "content": "A fatal case of systemic carnitine deficiency is reported. The patient suffered from slowly progressive muscle weakness since early childhood. After the age of 17 years her weakness progressed more rapidly until her death at the age of 20. A pregnancy during the last year of the patient's life was followed by rapid deterioration in her condition. An episode of renal insufficiency occurred at the age of 17 years and hepatomegaly, increased BSP dye retention and intermittent ketoacidosis were present during the last month of her life. Biopsy and autopsy specimens of muscle showed a lipid storage myopathy. Type 1 fibers were selectively severely affected, and many Type 1 fibers were atrophic. Abundant large mitochondria, some also containing abnormal inclusions, were also present in the muscle fibers. At autopsy there was marked accumulation of sudanophilic lipid deposits in all hepatocytes, in the renal tubular epithelial cells, and a patchy increase of lipid material was found in the myocardial fibers. There was marked carnitine deficiency in the patient's liver as well as muscel, while the carnitine palmityltransferase activities in these tissues were abnormally high. The basic metabolic abnormality is assumed to be a defect in carnitine biosynthesis.", "contents": "Fatal systemic carnitine deficiency with lipid storage in skeletal muscle, heart, liver and kidney. A fatal case of systemic carnitine deficiency is reported. The patient suffered from slowly progressive muscle weakness since early childhood. After the age of 17 years her weakness progressed more rapidly until her death at the age of 20. A pregnancy during the last year of the patient's life was followed by rapid deterioration in her condition. An episode of renal insufficiency occurred at the age of 17 years and hepatomegaly, increased BSP dye retention and intermittent ketoacidosis were present during the last month of her life. Biopsy and autopsy specimens of muscle showed a lipid storage myopathy. Type 1 fibers were selectively severely affected, and many Type 1 fibers were atrophic. Abundant large mitochondria, some also containing abnormal inclusions, were also present in the muscle fibers. At autopsy there was marked accumulation of sudanophilic lipid deposits in all hepatocytes, in the renal tubular epithelial cells, and a patchy increase of lipid material was found in the myocardial fibers. There was marked carnitine deficiency in the patient's liver as well as muscel, while the carnitine palmityltransferase activities in these tissues were abnormally high. The basic metabolic abnormality is assumed to be a defect in carnitine biosynthesis."}
{"id": "PMID:187739", "title": "Hereditary hypertrophic neuropathy in the trembler mouse. Part 1. Histopathological studies: light microscopy.", "content": "The Trembler mouse suffers from a dominantly inherited chronic hypertrophic neuropathy. Quantitative light-microscopic studies have been performed on Trembler peripheral nerves from birth to adulthood, and compared with the findings in age-matched control mice. Teased fibres of Trembler nerves contained virtually no myelin, nodes of Ranvier were difficult to identify, and supernumerary Schwann cells were prominent. Results of quantitative studies performed on the dorsal root ganglia and spinal cord of Trembler mice did not differ from those in controls. The density of myelinated fibres in the case of Tremblers was reduced at all ages when compared with controls, and there was a predominant loss of large diameter fibres.", "contents": "Hereditary hypertrophic neuropathy in the trembler mouse. Part 1. Histopathological studies: light microscopy. The Trembler mouse suffers from a dominantly inherited chronic hypertrophic neuropathy. Quantitative light-microscopic studies have been performed on Trembler peripheral nerves from birth to adulthood, and compared with the findings in age-matched control mice. Teased fibres of Trembler nerves contained virtually no myelin, nodes of Ranvier were difficult to identify, and supernumerary Schwann cells were prominent. Results of quantitative studies performed on the dorsal root ganglia and spinal cord of Trembler mice did not differ from those in controls. The density of myelinated fibres in the case of Tremblers was reduced at all ages when compared with controls, and there was a predominant loss of large diameter fibres."}
{"id": "PMID:187740", "title": "Hereditary hypertrophic neuropathy in the trembler mouse. Part 2. Histopathological studies: electron microscopy.", "content": "The Trembler mouse suffers from a dominantly inherited hypertrophic neuropathy. Electron microscopy, including a quantitative analysis of myelination was performed on the nerves of Trembler mice from birth to senility and compared with the findings in control mice. Axons in adult Trembler nerves were thinly myelinated and were surrounded by very few myelin lamellae which in turn were often uncompact circumferentially and longitudinally. Schwann cell cytoplasm was copious and had a normal content of organelles. Well-developed \"onion-bulb\" formations which consisted of thinly myelinated axons surrounded by empty membrane configurations were frequently seen. The initiation of myelination was studied. The diameter distribution of promyelin fibres of control and Trembler sciatic nerve at ages day 2, j, and 7 was calculated Myelination in Trembler nerves commenced on axons of larger diameters than controls. The effectiveness of myelination was studied by relating the number of turns of myelin to the axon area of control and Trembler sciatic nerves from age 2 days to adult mice. At all ages Trembler axons were less well myelinated than controls and the difference was more pronounced with age. Schwann cell activity was examined by relating the area of the Schwann cell cytoplasm to the area of the axon it invests. The relative amount of Schwann cell cytoplasm decreased progressively in control axons with age and as the axon became better myelinated. By contrast, that of Tremblers did not undergo a similar reduction as the animal matured and the relative amount of Schwann cell cytoplasm was markedly increased in adult Tremblers when compared with controls. The periodicity of control and Trembler compact myelin was compared. The myelin period of Trembler mouse was significantly greater than that of controls. The defect in Trembler peripheral nerves was considered to be that of dysmyelinogenesis. The Schwann cell was active but ineffective in the synthesis, compaction and maintenance of myelin.", "contents": "Hereditary hypertrophic neuropathy in the trembler mouse. Part 2. Histopathological studies: electron microscopy. The Trembler mouse suffers from a dominantly inherited hypertrophic neuropathy. Electron microscopy, including a quantitative analysis of myelination was performed on the nerves of Trembler mice from birth to senility and compared with the findings in control mice. Axons in adult Trembler nerves were thinly myelinated and were surrounded by very few myelin lamellae which in turn were often uncompact circumferentially and longitudinally. Schwann cell cytoplasm was copious and had a normal content of organelles. Well-developed \"onion-bulb\" formations which consisted of thinly myelinated axons surrounded by empty membrane configurations were frequently seen. The initiation of myelination was studied. The diameter distribution of promyelin fibres of control and Trembler sciatic nerve at ages day 2, j, and 7 was calculated Myelination in Trembler nerves commenced on axons of larger diameters than controls. The effectiveness of myelination was studied by relating the number of turns of myelin to the axon area of control and Trembler sciatic nerves from age 2 days to adult mice. At all ages Trembler axons were less well myelinated than controls and the difference was more pronounced with age. Schwann cell activity was examined by relating the area of the Schwann cell cytoplasm to the area of the axon it invests. The relative amount of Schwann cell cytoplasm decreased progressively in control axons with age and as the axon became better myelinated. By contrast, that of Tremblers did not undergo a similar reduction as the animal matured and the relative amount of Schwann cell cytoplasm was markedly increased in adult Tremblers when compared with controls. The periodicity of control and Trembler compact myelin was compared. The myelin period of Trembler mouse was significantly greater than that of controls. The defect in Trembler peripheral nerves was considered to be that of dysmyelinogenesis. The Schwann cell was active but ineffective in the synthesis, compaction and maintenance of myelin."}
{"id": "PMID:187741", "title": "Abducens nerve paralysis due to giant aneurysm in the medial carotid canal. Case report.", "content": "A case of a giant aneurysm located in the medial part of the carotid canal is reported. The patient had isolated abducens nerve paralysis that completely resolved after common carotid ligation in the neck.", "contents": "Abducens nerve paralysis due to giant aneurysm in the medial carotid canal. Case report. A case of a giant aneurysm located in the medial part of the carotid canal is reported. The patient had isolated abducens nerve paralysis that completely resolved after common carotid ligation in the neck."}
{"id": "PMID:187742", "title": "Myocardial uptake (rabbit) of six 99mTc-tagged pharmaceuticals and 85Sr after vasopressin-induced necrosis.", "content": "A new rapid method for producing myocardial necrosis in rabbits was developed, using percutaneous intramyocardial injection of vasopressin in peanut oil. The 15-min procedure resulted in a mortality rate of 15% and a success rate among surviving animals of 50%. When the lesions were 24 hr old, strontium-85 and a technetium-99m-tagged agent were injected intravenously simultaneously, and the animals were killed 1,6, and 24 hr later for tissue radioassay. Strontium-85 failed to accumulate appreciably in the lesions. Three bone-seeking technetium complexes (pyrophosphate, methylene diphosphonate, and imidodiphosphonate) produced lesion-to-normal myocardial ratios of 6,5, and 14, respectively, at 1 hr, and 20,30, and 33 at 6 hr. The ratios for 99mTc-glucoheptonate were only 2 at 1 hr and 4 at 6 hr, while the ratios of 99mTc-acetylcysteine and 99mTc-citrate were even lower.", "contents": "Myocardial uptake (rabbit) of six 99mTc-tagged pharmaceuticals and 85Sr after vasopressin-induced necrosis. A new rapid method for producing myocardial necrosis in rabbits was developed, using percutaneous intramyocardial injection of vasopressin in peanut oil. The 15-min procedure resulted in a mortality rate of 15% and a success rate among surviving animals of 50%. When the lesions were 24 hr old, strontium-85 and a technetium-99m-tagged agent were injected intravenously simultaneously, and the animals were killed 1,6, and 24 hr later for tissue radioassay. Strontium-85 failed to accumulate appreciably in the lesions. Three bone-seeking technetium complexes (pyrophosphate, methylene diphosphonate, and imidodiphosphonate) produced lesion-to-normal myocardial ratios of 6,5, and 14, respectively, at 1 hr, and 20,30, and 33 at 6 hr. The ratios for 99mTc-glucoheptonate were only 2 at 1 hr and 4 at 6 hr, while the ratios of 99mTc-acetylcysteine and 99mTc-citrate were even lower."}
{"id": "PMID:187744", "title": "Electron microscopic observations of \"keratin pools\" in chronic hyperplastic oral mucosa.", "content": "\"Keratin pools,\" previously characterized clinically and histochemically in the superficial epithelium of chronic hyperplastic oral mucosa, were studied by light and electron microscopy. These occured as small beaded and larger coalescent masses which varied in metachromasia. Ultrastructurally, the \"keratin pools\" consisted of electron-dense, amorphous or finely-granular material developing and coalescing, chiefly as extracellular deposits. The \"pools\" frequently possessed a layered arrangement alternating with cells having distinct tonofilaments, desmosomes, and definite cell membranes. Occasional bands of filamentous-like material, possibly representing tonofilament bundles, were observed in some \"pools.\"", "contents": "Electron microscopic observations of \"keratin pools\" in chronic hyperplastic oral mucosa. \"Keratin pools,\" previously characterized clinically and histochemically in the superficial epithelium of chronic hyperplastic oral mucosa, were studied by light and electron microscopy. These occured as small beaded and larger coalescent masses which varied in metachromasia. Ultrastructurally, the \"keratin pools\" consisted of electron-dense, amorphous or finely-granular material developing and coalescing, chiefly as extracellular deposits. The \"pools\" frequently possessed a layered arrangement alternating with cells having distinct tonofilaments, desmosomes, and definite cell membranes. Occasional bands of filamentous-like material, possibly representing tonofilament bundles, were observed in some \"pools.\""}
{"id": "PMID:187745", "title": "A postaxial polydactyly-dental-vertebral syndrome.", "content": "Three patients with postaxial polydactyly and other abnormalities of the hands and feet, hypoplasia and fusion of the vertebral bodies, and dental abnormalities are reported. Two were sisters born to normal unrelated parents; the other patient was the male offspring of a consanguineous marriage. We suggest that this constellation of abnormalities represents a recessively inherited syndrome.", "contents": "A postaxial polydactyly-dental-vertebral syndrome. Three patients with postaxial polydactyly and other abnormalities of the hands and feet, hypoplasia and fusion of the vertebral bodies, and dental abnormalities are reported. Two were sisters born to normal unrelated parents; the other patient was the male offspring of a consanguineous marriage. We suggest that this constellation of abnormalities represents a recessively inherited syndrome."}
{"id": "PMID:187746", "title": "Acid hydrolase activity during growth and encystment in Acanthamoeba castellanii.", "content": "The activity and sedimentation of acid phosphatase (APase), acid deoxyribonuclease (DNase), and acid ribonuclease (RNase) were investigated throughout growth and encystment in Acanthamoeba castellanii. The activities/mg protein of all 3 hydrolases are high in young cultures and decrease to constant levels in postlog cells. The RNase activity/ameba decreases 50% during growth, whereas the activity/cell of both APase and DNase remains constant. The percent sedimentation at 20,000 g of all 3 enzymes gradually increases from about 40% in midlog to a plateau of 80% in postlog cells. During encystment, the sedimentation behavior of RNase differs from that of APase and DNase. Encystment is characterized by a differential decrease in the activity/cell of the 3 hydrolases, with RNase decreasing most rapidly and APase least rapidly. APase is unique in that a transient increase of its specific activity is noted during encystment, even though its activity/cell is decreasing.", "contents": "Acid hydrolase activity during growth and encystment in Acanthamoeba castellanii. The activity and sedimentation of acid phosphatase (APase), acid deoxyribonuclease (DNase), and acid ribonuclease (RNase) were investigated throughout growth and encystment in Acanthamoeba castellanii. The activities/mg protein of all 3 hydrolases are high in young cultures and decrease to constant levels in postlog cells. The RNase activity/ameba decreases 50% during growth, whereas the activity/cell of both APase and DNase remains constant. The percent sedimentation at 20,000 g of all 3 enzymes gradually increases from about 40% in midlog to a plateau of 80% in postlog cells. During encystment, the sedimentation behavior of RNase differs from that of APase and DNase. Encystment is characterized by a differential decrease in the activity/cell of the 3 hydrolases, with RNase decreasing most rapidly and APase least rapidly. APase is unique in that a transient increase of its specific activity is noted during encystment, even though its activity/cell is decreasing."}
{"id": "PMID:187748", "title": "Evidence for species-specific substrate-site-directed inactivation of rabbit adenylate kinase by N6-(6-iodoacetamido-n-hexyl)adenosine 5'-triphosphate.", "content": "Adenosine 5'-triphosphate (ATP) derivatives bearing iodoacetylamino-n-alkyl substituents [(CH2)nNHCOCH2I] on N6 were synthesized as potential ATP-site-directed irreversible inhibitors of adenylate kinases from rabbit, pig, and carp muscle. When n was 5 no enzyme was progressively inhibited (inactivated) by 1 mM inhibitor under the test conditions (6 h at 0 degrees); when n was 6 the rabbit enzyme was 76% inactivated by 0.79 mM inhibitor whereas the pig and carp enzymes were unaffected by 2.76 mM inhibitor; when n was 7, 1 mM inhibitor inactivated 14% of the rabbit enzyme and did not inactivate the pig and carp enzymes; when n was 8, all enzymes were inactivated 11-15% by 1 mM inhibitor. No inactivation occurred when the iodine of the hexamethylene analogue was replaced by hydrogen. The selective effect occured also in mixtures of the rabbit and pig enzymes and evidence could not be found that the hexamethylene analogue was activated by the rabbit enzyme or deactivated by the pig and carp preparations. The species-specific inactivation in concluded from various lines of evidence to be ATP-site-directed and is attributed to alkylation of an amino acid residue of the rabbit enzyme which in the pig and carp enzymes is absent, inaccessible, or less reactive. These and previous studies with several other enzymes provide evidence that substrate-site-directed agents capable of bonding covalently to an amino acid residue outside the substrate site can be designed to exert species-specific or tissue-specific irreversible inhibition of target enzymes.", "contents": "Evidence for species-specific substrate-site-directed inactivation of rabbit adenylate kinase by N6-(6-iodoacetamido-n-hexyl)adenosine 5'-triphosphate. Adenosine 5'-triphosphate (ATP) derivatives bearing iodoacetylamino-n-alkyl substituents [(CH2)nNHCOCH2I] on N6 were synthesized as potential ATP-site-directed irreversible inhibitors of adenylate kinases from rabbit, pig, and carp muscle. When n was 5 no enzyme was progressively inhibited (inactivated) by 1 mM inhibitor under the test conditions (6 h at 0 degrees); when n was 6 the rabbit enzyme was 76% inactivated by 0.79 mM inhibitor whereas the pig and carp enzymes were unaffected by 2.76 mM inhibitor; when n was 7, 1 mM inhibitor inactivated 14% of the rabbit enzyme and did not inactivate the pig and carp enzymes; when n was 8, all enzymes were inactivated 11-15% by 1 mM inhibitor. No inactivation occurred when the iodine of the hexamethylene analogue was replaced by hydrogen. The selective effect occured also in mixtures of the rabbit and pig enzymes and evidence could not be found that the hexamethylene analogue was activated by the rabbit enzyme or deactivated by the pig and carp preparations. The species-specific inactivation in concluded from various lines of evidence to be ATP-site-directed and is attributed to alkylation of an amino acid residue of the rabbit enzyme which in the pig and carp enzymes is absent, inaccessible, or less reactive. These and previous studies with several other enzymes provide evidence that substrate-site-directed agents capable of bonding covalently to an amino acid residue outside the substrate site can be designed to exert species-specific or tissue-specific irreversible inhibition of target enzymes."}
{"id": "PMID:187749", "title": "Iodo-bis(quaternary ammonium) salts. Potential cartilage-selective x-ray contrast agents.", "content": "Bis(quaternary ammonium) compounds in which one or both quaternary nitrogens bear iodinated benzyl moieties and the charged centers are separated by 2, 4, 6, or 10 methylene units have been synthesized and evaluted for (a) binding to cartilaginous material, (b) radiocontrast characteristics, and (c) in vitro pharmacological effects. Also prepared was 1,5-diiodo-2,4-bis(beta-trimethylammonioethyl)benzene diiodide, an analogue in which the iodinated aryl group lies between the charged nitrogen centers. Biological studies show that these compounds bind to cartilage but at relatively slow rates and with low persistence, resulting in low and transient levels of radiopacity. In common with simpler bisquaternary compounds, these compounds block synaptic transmission.", "contents": "Iodo-bis(quaternary ammonium) salts. Potential cartilage-selective x-ray contrast agents. Bis(quaternary ammonium) compounds in which one or both quaternary nitrogens bear iodinated benzyl moieties and the charged centers are separated by 2, 4, 6, or 10 methylene units have been synthesized and evaluted for (a) binding to cartilaginous material, (b) radiocontrast characteristics, and (c) in vitro pharmacological effects. Also prepared was 1,5-diiodo-2,4-bis(beta-trimethylammonioethyl)benzene diiodide, an analogue in which the iodinated aryl group lies between the charged nitrogen centers. Biological studies show that these compounds bind to cartilage but at relatively slow rates and with low persistence, resulting in low and transient levels of radiopacity. In common with simpler bisquaternary compounds, these compounds block synaptic transmission."}
{"id": "PMID:187750", "title": "Design of substrate-site-directed inhibitors of adenylate kinase and hexokinase. Effect of substrate substituents on affinity on affinity for the adenine nucleotide sites.", "content": "Nineteen derivatives of adenosine 5'-phosphate (AMP) bearing acylaminomethyl, acetoxy, or alkylaminomethyl substituents on the phosphate-ribose bridge (5' and O-5' positions) of AMP together with 2',3'-O-ethylidene, 2',3',-O-isopropylidene, and 2',3'-di-O-acetyl derivatives of AMP have been synthesized. Their substrate and/or competitive inhibitor properties with pig rabbit muscle AMP kinases indicate that all the substituents except 2',3'-O-ethlidene with the pig enzyme permitted binding of AMP at its enzymic site. Determination of enzyme-inhibitor dissociation constants showed that several compounds with substituents on the ribose-phosphate bridge bind as well or better than AMP. The affinity is ascribed in part to interaction between substituents and a lipophilic region of the enzymes adjacent to the ribose-phosphate bridge in the enzyme-AMP complexes. The enzyme-inhibitor dissociation constants reveal a structural dissimilarity between the pig and rabbit enzymes in the vicinity of the lipophilic region. The substrate and inhibitor properties of eight ATP derivatives gave evidence that affinity of ATP for its substrate site on the AMP kinases is compatible with acetyl- or chloroacetylaminomethyl groups at the phosphate-ribose bridge or with 2',3'-O-ethylidene or isopropylidene residues. The yeast hexokinase-ATP complex tolerated an acetylaminomethyl group at C-5' or a benzoylaminomethyl group adjacent to O-5'. The present findings regarding substituent tolerance could be used in the design of adenine nucleotide site-directed irreversible inhibitors.", "contents": "Design of substrate-site-directed inhibitors of adenylate kinase and hexokinase. Effect of substrate substituents on affinity on affinity for the adenine nucleotide sites. Nineteen derivatives of adenosine 5'-phosphate (AMP) bearing acylaminomethyl, acetoxy, or alkylaminomethyl substituents on the phosphate-ribose bridge (5' and O-5' positions) of AMP together with 2',3'-O-ethylidene, 2',3',-O-isopropylidene, and 2',3'-di-O-acetyl derivatives of AMP have been synthesized. Their substrate and/or competitive inhibitor properties with pig rabbit muscle AMP kinases indicate that all the substituents except 2',3'-O-ethlidene with the pig enzyme permitted binding of AMP at its enzymic site. Determination of enzyme-inhibitor dissociation constants showed that several compounds with substituents on the ribose-phosphate bridge bind as well or better than AMP. The affinity is ascribed in part to interaction between substituents and a lipophilic region of the enzymes adjacent to the ribose-phosphate bridge in the enzyme-AMP complexes. The enzyme-inhibitor dissociation constants reveal a structural dissimilarity between the pig and rabbit enzymes in the vicinity of the lipophilic region. The substrate and inhibitor properties of eight ATP derivatives gave evidence that affinity of ATP for its substrate site on the AMP kinases is compatible with acetyl- or chloroacetylaminomethyl groups at the phosphate-ribose bridge or with 2',3'-O-ethylidene or isopropylidene residues. The yeast hexokinase-ATP complex tolerated an acetylaminomethyl group at C-5' or a benzoylaminomethyl group adjacent to O-5'. The present findings regarding substituent tolerance could be used in the design of adenine nucleotide site-directed irreversible inhibitors."}
{"id": "PMID:187751", "title": "Purity of staphylococcal delta-haemolysin obtained by three different procedures.", "content": "Three methods at present available for the purification of staphylococcal delta-haemolysin were compared as to the purity and identify of the product obtained. None yielded a pure preparation of delta-haemolysin; one of the three preparations did not contain demonstrable delta-haemolysin when tested electrophoretically, but it contained deoxyribonuclease, penicillinase, phosphatase and alpha-haemolysin. The second preparation had delta-haemolysin activity and was free of alpha-haemolysin, but it contained lipase, egg-yolk factor, esterase, deoxyribonuclease, penicillinase, phosphatase and hyaluronidase. The third preparation contained all of the products mentioned above, except phosphatase, and it also contained alpha-haemolysin, staphylokinase, lysozyme and caseinase. These findings are discussed with special reference to the requirement for criteria of purity in work with staphylococcal products.", "contents": "Purity of staphylococcal delta-haemolysin obtained by three different procedures. Three methods at present available for the purification of staphylococcal delta-haemolysin were compared as to the purity and identify of the product obtained. None yielded a pure preparation of delta-haemolysin; one of the three preparations did not contain demonstrable delta-haemolysin when tested electrophoretically, but it contained deoxyribonuclease, penicillinase, phosphatase and alpha-haemolysin. The second preparation had delta-haemolysin activity and was free of alpha-haemolysin, but it contained lipase, egg-yolk factor, esterase, deoxyribonuclease, penicillinase, phosphatase and hyaluronidase. The third preparation contained all of the products mentioned above, except phosphatase, and it also contained alpha-haemolysin, staphylokinase, lysozyme and caseinase. These findings are discussed with special reference to the requirement for criteria of purity in work with staphylococcal products."}
{"id": "PMID:187758", "title": "Various degrees of susceptibility of different stocks of rats to N-2-fluorenyldiacetamide hepatic carcinogenesis.", "content": "Outbred Osborne Mendel, Japanese, Wistar, NIH Black, and Sorague-Dawley male rats 12 weeks of age ingested 0.025% N-2-fluorenyldiacetamide in a semisynthetic diet Sprague-Daeley and NIH Black male rats were most susceptible to the development of carcinomas and cirrhosis of the liver and also had the highest incidence of metastases. More and larger carcinomas per liver and more poorly differentiated and undifferentiated carcinomas were found, as well as more advanced cirrhosis, Japanese and Wistar male rats were susceptible, but less so, to hepatic carcinogenesis and cirrhosis. These rats had fewer and smaller hepatic carcinomas per liver, and the neoplasms were well differentiated. By contrast, Osborne Mendel male rats were least susceptible to hepatic carcinogenesis and cirrhosis.", "contents": "Various degrees of susceptibility of different stocks of rats to N-2-fluorenyldiacetamide hepatic carcinogenesis. Outbred Osborne Mendel, Japanese, Wistar, NIH Black, and Sorague-Dawley male rats 12 weeks of age ingested 0.025% N-2-fluorenyldiacetamide in a semisynthetic diet Sprague-Daeley and NIH Black male rats were most susceptible to the development of carcinomas and cirrhosis of the liver and also had the highest incidence of metastases. More and larger carcinomas per liver and more poorly differentiated and undifferentiated carcinomas were found, as well as more advanced cirrhosis, Japanese and Wistar male rats were susceptible, but less so, to hepatic carcinogenesis and cirrhosis. These rats had fewer and smaller hepatic carcinomas per liver, and the neoplasms were well differentiated. By contrast, Osborne Mendel male rats were least susceptible to hepatic carcinogenesis and cirrhosis."}
{"id": "PMID:187759", "title": "Persistence of immunoglobulin and complement components C4 and C3 bound to guinea pig tumor cells.", "content": "Guinea pig hepatoma cells (line-10) growing as ascites were studied for the presence of immunoglobulin, C4, and C3 (components of complement) on their surfaces. Immunoglobulin, C4, and C3 content increased with length of time spent in the peritoneal cavity. The persistence of these factors bound in vivo or in vitro was also determined. Complement-fixing (CF) activity of cellbound antibody disappeared from the surface more rapidly at 37 degrees C than at 4 degrees C; the continued presence of cellbound immunoglobulin in non-complement-fixing form could be demonostrated at either temperature. No CF activity was released into the medium. C4 and C3 were released into the medium and could be demonstrated in the medium by immunochemical methods.", "contents": "Persistence of immunoglobulin and complement components C4 and C3 bound to guinea pig tumor cells. Guinea pig hepatoma cells (line-10) growing as ascites were studied for the presence of immunoglobulin, C4, and C3 (components of complement) on their surfaces. Immunoglobulin, C4, and C3 content increased with length of time spent in the peritoneal cavity. The persistence of these factors bound in vivo or in vitro was also determined. Complement-fixing (CF) activity of cellbound antibody disappeared from the surface more rapidly at 37 degrees C than at 4 degrees C; the continued presence of cellbound immunoglobulin in non-complement-fixing form could be demonostrated at either temperature. No CF activity was released into the medium. C4 and C3 were released into the medium and could be demonstrated in the medium by immunochemical methods."}
{"id": "PMID:187760", "title": "Herpesvirus saimiri-induced malignant lymphoma in rabbits.", "content": "Of 9 New Zealand White rabbits inoculated at multiple sc and im sites with a single dose of Herpesvirus saimiri (HVS), 2 developed malignant lymphomas 40-50 days post inoculation. At least 1 animal developed a terminal leukemic phase of the disease. HVS was isolated from the oral and conjunctival swabs and blood and tissue lymphocytes, but not from monolayer cell cultures derived from kidney or lung tissues of the diseased animals. The inoculated rabbits developed low titers of neutralizing antibodies against the virus. Antibodies against HVS specific early and late antigens were not detected in the sera of 7 animals that failed to develop clinical disease, but were detected in the serum of the 1 rabbit with lymphoma. The immunologic response of rabbits to HVS infection was compared to similar responses in infected nonhuman primates.", "contents": "Herpesvirus saimiri-induced malignant lymphoma in rabbits. Of 9 New Zealand White rabbits inoculated at multiple sc and im sites with a single dose of Herpesvirus saimiri (HVS), 2 developed malignant lymphomas 40-50 days post inoculation. At least 1 animal developed a terminal leukemic phase of the disease. HVS was isolated from the oral and conjunctival swabs and blood and tissue lymphocytes, but not from monolayer cell cultures derived from kidney or lung tissues of the diseased animals. The inoculated rabbits developed low titers of neutralizing antibodies against the virus. Antibodies against HVS specific early and late antigens were not detected in the sera of 7 animals that failed to develop clinical disease, but were detected in the serum of the 1 rabbit with lymphoma. The immunologic response of rabbits to HVS infection was compared to similar responses in infected nonhuman primates."}
{"id": "PMID:187761", "title": "Carcinogenicity of Camellia sinensis (tea) and some tannin-containing folk medicinal herbs administered subcutaneously in rats.", "content": "In an attempt to correlate the high incidence of esophageal carcinoma in natives of certain places with their habit of using herbaceous folk medicines, we performed bioassays of several plant extracts and the fractions prepared from them. Fourteen extracts and fractions from 6 plants were injected sc into NIH Black rats. The tannin fractions from Quercus falcata pagodaefolia, Diospyros virginiana, and Camellia sinensis were very active and produced tumors at the injection site in 66% or more of the treated animals. Tannin fractions from 3 other plants and total aqueous extracts from 5 to 6 tested plants were also tumorigenic rats. The induced tumors were malignant fibrous histiocytomas similar, if not identical, to those encountered in humans. The experiment indicated a possibility of induction of tumor in man by the tested plant materials.", "contents": "Carcinogenicity of Camellia sinensis (tea) and some tannin-containing folk medicinal herbs administered subcutaneously in rats. In an attempt to correlate the high incidence of esophageal carcinoma in natives of certain places with their habit of using herbaceous folk medicines, we performed bioassays of several plant extracts and the fractions prepared from them. Fourteen extracts and fractions from 6 plants were injected sc into NIH Black rats. The tannin fractions from Quercus falcata pagodaefolia, Diospyros virginiana, and Camellia sinensis were very active and produced tumors at the injection site in 66% or more of the treated animals. Tannin fractions from 3 other plants and total aqueous extracts from 5 to 6 tested plants were also tumorigenic rats. The induced tumors were malignant fibrous histiocytomas similar, if not identical, to those encountered in humans. The experiment indicated a possibility of induction of tumor in man by the tested plant materials."}
{"id": "PMID:187762", "title": "Nucleic acids from subcellular fractions of N-nitrosodiethylamine-induced hepatoma in mice.", "content": "During eight successive isologous passages of hepatoma induced in male C3HA mice by N-nitrosodiethylamine, no common features of tumor progression were observed, although both the mitotic pattern and ploidy differed from generation to generation. These additional cytologic criteria allowed the biochemical examination of material least changed due to tumor progression. Tumor nDNA's were characterized by greater actinomycin D (AD)- and acridine orange (AO)-binding abilities than were normal nDNA's; this could have resulted from a higher proportion of double-stranded regions in tumor DNA. Isolated tumor deoxyribonucleoprotein had both lower template activity in an RNA polymerase system and fewer AD- and AO-binding sites, when compared with the activity and sites from normal mouse liver. RNA-DNA hybridization data with the above-mentioned findings showed that in hepatoma, part of the nuclear genome was repressed. Also, RNA \"new classes\" appeared and a certain proportion of nuclear genes controlling mitochondrial protein biosynthesis were derepressed in tumor mitochondria. The hybridization of mitochondrial RNA (mtRNA) and DNA revealed new classes of pulse-labeled RNA's in in vitro-incubated liver mitochondria that were absent from intact cell organelles; the hybridization properties of in vivo- and in vitro-formed hepatoma mtRNA's were similar. Competition and hybridization experiments demonstrated that in tumor mitochondria in vivo, some new classes of RNA existed. Hepatoma mitochondrial mRNA had a higher metabolic stability than did normal mRNA.", "contents": "Nucleic acids from subcellular fractions of N-nitrosodiethylamine-induced hepatoma in mice. During eight successive isologous passages of hepatoma induced in male C3HA mice by N-nitrosodiethylamine, no common features of tumor progression were observed, although both the mitotic pattern and ploidy differed from generation to generation. These additional cytologic criteria allowed the biochemical examination of material least changed due to tumor progression. Tumor nDNA's were characterized by greater actinomycin D (AD)- and acridine orange (AO)-binding abilities than were normal nDNA's; this could have resulted from a higher proportion of double-stranded regions in tumor DNA. Isolated tumor deoxyribonucleoprotein had both lower template activity in an RNA polymerase system and fewer AD- and AO-binding sites, when compared with the activity and sites from normal mouse liver. RNA-DNA hybridization data with the above-mentioned findings showed that in hepatoma, part of the nuclear genome was repressed. Also, RNA \"new classes\" appeared and a certain proportion of nuclear genes controlling mitochondrial protein biosynthesis were derepressed in tumor mitochondria. The hybridization of mitochondrial RNA (mtRNA) and DNA revealed new classes of pulse-labeled RNA's in in vitro-incubated liver mitochondria that were absent from intact cell organelles; the hybridization properties of in vivo- and in vitro-formed hepatoma mtRNA's were similar. Competition and hybridization experiments demonstrated that in tumor mitochondria in vivo, some new classes of RNA existed. Hepatoma mitochondrial mRNA had a higher metabolic stability than did normal mRNA."}
{"id": "PMID:187763", "title": "Elevated adenosine 3',5'-cyclic monophosphate levels in human and animal tumors in vivo.", "content": "Cyclic AMP (cAMP) levels were measured in several animal and human tumors and in normal human tissues. Malignant tissues did not appear to be deficient in cAMP.", "contents": "Elevated adenosine 3',5'-cyclic monophosphate levels in human and animal tumors in vivo. Cyclic AMP (cAMP) levels were measured in several animal and human tumors and in normal human tissues. Malignant tissues did not appear to be deficient in cAMP."}
{"id": "PMID:187764", "title": "Adenosine 3',5'-cyclic monophosphate levels in x-ray-induced small-bowel adenocarcinoma in the rat.", "content": "X-ray-induced adenocarcinomas in the small bowels of outbred Lewis Brown Norway and Holtzman rats contained significantly lower concentrations of adenosine 3',5'-cyclic monophosphate than did normal rat intestinal tissue. No significant differences were observed between the intracellular concentrations of the nucleotide in the normal rat small bowel and those occurring in normal-appearing intestinal tissue exposed to tumor induction conditions.", "contents": "Adenosine 3',5'-cyclic monophosphate levels in x-ray-induced small-bowel adenocarcinoma in the rat. X-ray-induced adenocarcinomas in the small bowels of outbred Lewis Brown Norway and Holtzman rats contained significantly lower concentrations of adenosine 3',5'-cyclic monophosphate than did normal rat intestinal tissue. No significant differences were observed between the intracellular concentrations of the nucleotide in the normal rat small bowel and those occurring in normal-appearing intestinal tissue exposed to tumor induction conditions."}
{"id": "PMID:187765", "title": "Nonimmune and immune surveillance. I. Growth of tumors and normal fetal tissues grafted into newborn mice.", "content": "Growth of various fetal tissues and transplantable tumors in syngeneic newborn and adult mice [BALB/c, DBA/2, and (CBA X C57BL/6J)F1] was compared. Fetal skin, a mixture of all fetal tissues, and tumors were transplanted. The tumors arose spontaneously [hepatomas, mammary gland adenocarcinoma (MGAC)] or resulted from malignant conversion of ectopic transplants either of fetal tissues (urinary bladder carcinoma, adenocarcinoma of small intestine, stomach sarcoma) or of adult animal tissues (ovarian carcinoma) in the syngeneic system. The growth of fetal skin transplants and teratomas, which developed after transplantation of minced tissue from 18- to 20-day and 12- to 14-day fetuses, was considerably inferior in newborn syngeneic recipients, as compared with similar transplants in adults. Inhibition of tumor growth observed in newborn animals was manifested in prolongation of latent period before tumor node appearance and in slowing of growth rate of developed tumors. One of six tumors studied (MGAC) grew at the same rate in newborn and adult recipients. It was suggested that a special type of cellular and/or humoral mechanisms controlling tumor growth exists in newborns. The activity of such factors was conceivably based on fetal tumor antigens as targets. We assumed that weakly antigenic and strongly antigenic tumors behaved differently in respect to nonimmune and immune surveillance mechanisms.", "contents": "Nonimmune and immune surveillance. I. Growth of tumors and normal fetal tissues grafted into newborn mice. Growth of various fetal tissues and transplantable tumors in syngeneic newborn and adult mice [BALB/c, DBA/2, and (CBA X C57BL/6J)F1] was compared. Fetal skin, a mixture of all fetal tissues, and tumors were transplanted. The tumors arose spontaneously [hepatomas, mammary gland adenocarcinoma (MGAC)] or resulted from malignant conversion of ectopic transplants either of fetal tissues (urinary bladder carcinoma, adenocarcinoma of small intestine, stomach sarcoma) or of adult animal tissues (ovarian carcinoma) in the syngeneic system. The growth of fetal skin transplants and teratomas, which developed after transplantation of minced tissue from 18- to 20-day and 12- to 14-day fetuses, was considerably inferior in newborn syngeneic recipients, as compared with similar transplants in adults. Inhibition of tumor growth observed in newborn animals was manifested in prolongation of latent period before tumor node appearance and in slowing of growth rate of developed tumors. One of six tumors studied (MGAC) grew at the same rate in newborn and adult recipients. It was suggested that a special type of cellular and/or humoral mechanisms controlling tumor growth exists in newborns. The activity of such factors was conceivably based on fetal tumor antigens as targets. We assumed that weakly antigenic and strongly antigenic tumors behaved differently in respect to nonimmune and immune surveillance mechanisms."}
{"id": "PMID:187766", "title": "Natural occurrence of tumors in mouse strains with different xenotropic and ecotropic endogenous viruses.", "content": "Natural tumor incidence and type C virus expression in HIH Swiss and BALB/c mice were investigated. The BALB/c mice showed a moderate incidence of lymphoreticular tumors containing infectious ecotropic virus. A second class of lymphoreticular tumors occurred with approximately the same incidence in both strains; though infectious virus could not be isolated from it, it contained the antigens of a common xenotropic virus. These xenotropic viral antigens were found in all NIH Swiss and BALB/c tumors examined and in normal hematopoietic tissues as well. The relationship between different classes of endogenous viruses and tumor development was discussed.", "contents": "Natural occurrence of tumors in mouse strains with different xenotropic and ecotropic endogenous viruses. Natural tumor incidence and type C virus expression in HIH Swiss and BALB/c mice were investigated. The BALB/c mice showed a moderate incidence of lymphoreticular tumors containing infectious ecotropic virus. A second class of lymphoreticular tumors occurred with approximately the same incidence in both strains; though infectious virus could not be isolated from it, it contained the antigens of a common xenotropic virus. These xenotropic viral antigens were found in all NIH Swiss and BALB/c tumors examined and in normal hematopoietic tissues as well. The relationship between different classes of endogenous viruses and tumor development was discussed."}
{"id": "PMID:187767", "title": "Immunologic identification of Epstein-Barr virus early antigen in a P3HR-1 cell extract.", "content": "We extracted the Epstein-Barr soluble antigen (EBSA) from the P3HR-1 human lymphoid cell line, which carries the Epstein-Barr virus (EBV), after P3HR-1 cells were activated with 5-iodo-2'-deoxyuridine. EBSA was identified as the early antigen (EA) complex by immunodiffusion and blocking immunofluorescence tests with high-titered human antiserum to EA. The identity of the EA complex was confirmed with antiserum to EA prepared in rabbits and adsorbed to assure its immunologic specificity. The EA was partially purified on Sephadex G-200. Further characterization by immunoelectrophoresis showed that the EBSA moved rapidly toward the anode. This indicated a highly negative charge. EBSA appeared to be distinct from the previously described complement-fixing S-antigen. It was demonstrable only in EA-producer lymphoid cell lines and reacted specifically with human antiserum to EA, whereas the S-antigen was found in all EBV-carrying lymphoid cell lines and reacted with all EBV antibody-positive human antisera.", "contents": "Immunologic identification of Epstein-Barr virus early antigen in a P3HR-1 cell extract. We extracted the Epstein-Barr soluble antigen (EBSA) from the P3HR-1 human lymphoid cell line, which carries the Epstein-Barr virus (EBV), after P3HR-1 cells were activated with 5-iodo-2'-deoxyuridine. EBSA was identified as the early antigen (EA) complex by immunodiffusion and blocking immunofluorescence tests with high-titered human antiserum to EA. The identity of the EA complex was confirmed with antiserum to EA prepared in rabbits and adsorbed to assure its immunologic specificity. The EA was partially purified on Sephadex G-200. Further characterization by immunoelectrophoresis showed that the EBSA moved rapidly toward the anode. This indicated a highly negative charge. EBSA appeared to be distinct from the previously described complement-fixing S-antigen. It was demonstrable only in EA-producer lymphoid cell lines and reacted specifically with human antiserum to EA, whereas the S-antigen was found in all EBV-carrying lymphoid cell lines and reacted with all EBV antibody-positive human antisera."}
{"id": "PMID:187768", "title": "Suppression of the avian sarcoma virus genome in 8-azaquanine-resistant, transformed, hamster cells.", "content": "The avian sarcoma virus genome (Schmidt-Ruppin strain) in transformed hamster cells resistant to 8-azaquanine [Ha(SR)AG-50] was strongly suppressed. The suppression was genetically stable and could not be overcome by attempts at induction with 5-iodo-2'-deoxyuridine. Fusion of hamster cells, which had suppressed virus genome, with chicken Rous-associated virus (RAV-1)-preinfected cells easily rescued the sarcoma virus. The rescued virus had envelope properties of RAV-1, as determined by viral interference, virus neutralization, and plating on genetically resistant chicken cells. By repeatedly cloning the rescued virus, we determined that virus recombined in the rescue experiment and that the recombinant virus had the envelope properties of helper virus used for its rescue. Cells with suppressed avian sarcoma virus genome were suitable for preparation of different recombinant viruses.", "contents": "Suppression of the avian sarcoma virus genome in 8-azaquanine-resistant, transformed, hamster cells. The avian sarcoma virus genome (Schmidt-Ruppin strain) in transformed hamster cells resistant to 8-azaquanine [Ha(SR)AG-50] was strongly suppressed. The suppression was genetically stable and could not be overcome by attempts at induction with 5-iodo-2'-deoxyuridine. Fusion of hamster cells, which had suppressed virus genome, with chicken Rous-associated virus (RAV-1)-preinfected cells easily rescued the sarcoma virus. The rescued virus had envelope properties of RAV-1, as determined by viral interference, virus neutralization, and plating on genetically resistant chicken cells. By repeatedly cloning the rescued virus, we determined that virus recombined in the rescue experiment and that the recombinant virus had the envelope properties of helper virus used for its rescue. Cells with suppressed avian sarcoma virus genome were suitable for preparation of different recombinant viruses."}
{"id": "PMID:187769", "title": "Nephroblastoma in the rat: histology of a spontaneous tumor, identity with respect to renal mesenchymal neoplasms, and a review of previously recorded cases.", "content": "The histology of a spontaneously occurring neoplasm of the rat kidney conforming to a classification of nephroblastoma is described and compared with that of N-nitrosodimethylamine-induced renal mesenchymal tumors. This rat nephroblastoma was an encapsulated epitheloid neoplasm with a uniform histologic pattern. Clumps of densely crowded, hyperchromatic cells frequently associated with central, well-differentiated ducts were supported by a less cellular, interconnecting stroma of loose areolar or mature fibrous connective tissue. Neoplastic cells were organized into primitive, ill-defined tubular formations. The neoplastic cell component strongly resembled metanephrogenic blastema. In contrast, the renal mesenchymal tumor was nonencapsulated and consisted of a heterogeneous mixture of connective tissue elements including fibroblast-like spindle cells, smooth muscle, and embryonic mesenchyme that engulfed and sequestered preexisting renal tubules and glomeruli. The separate morphologic identities and apparently unrelated existence of rat nephroblastoma and renal mesenchymal tumor were stressed. The rat nephroblastoma morphologically resembled the malignant epithelial component of human Wilms' tumor, whereas rat renal mesenchymal tumor appeared to have counter-parts in the mesenchymal component of Wilms' tumor and in congenital mesoblastic nephroma (leiomyomatous hamartoma) of infancy. The histologic descriptions of previously recorded occurrences of spontaneous and experimentally induced rat neoplasma classified as nephroblastoma or its synonyms were reevaluated in comparison to the present case. In all but four instances, in which sufficient histologic detail was provided in previous reports, a consistent histologic pattern emerged for this neoplasm in the rat.", "contents": "Nephroblastoma in the rat: histology of a spontaneous tumor, identity with respect to renal mesenchymal neoplasms, and a review of previously recorded cases. The histology of a spontaneously occurring neoplasm of the rat kidney conforming to a classification of nephroblastoma is described and compared with that of N-nitrosodimethylamine-induced renal mesenchymal tumors. This rat nephroblastoma was an encapsulated epitheloid neoplasm with a uniform histologic pattern. Clumps of densely crowded, hyperchromatic cells frequently associated with central, well-differentiated ducts were supported by a less cellular, interconnecting stroma of loose areolar or mature fibrous connective tissue. Neoplastic cells were organized into primitive, ill-defined tubular formations. The neoplastic cell component strongly resembled metanephrogenic blastema. In contrast, the renal mesenchymal tumor was nonencapsulated and consisted of a heterogeneous mixture of connective tissue elements including fibroblast-like spindle cells, smooth muscle, and embryonic mesenchyme that engulfed and sequestered preexisting renal tubules and glomeruli. The separate morphologic identities and apparently unrelated existence of rat nephroblastoma and renal mesenchymal tumor were stressed. The rat nephroblastoma morphologically resembled the malignant epithelial component of human Wilms' tumor, whereas rat renal mesenchymal tumor appeared to have counter-parts in the mesenchymal component of Wilms' tumor and in congenital mesoblastic nephroma (leiomyomatous hamartoma) of infancy. The histologic descriptions of previously recorded occurrences of spontaneous and experimentally induced rat neoplasma classified as nephroblastoma or its synonyms were reevaluated in comparison to the present case. In all but four instances, in which sufficient histologic detail was provided in previous reports, a consistent histologic pattern emerged for this neoplasm in the rat."}
{"id": "PMID:187770", "title": "Antipyretic and antiviral action of vitamin A in Moloney sarcoma virus- and poxvirus-inoculated mice.", "content": "Six week-old male CBA/J mice fed a commercial powdered laboratory chow or the same chow supplemented with vitamin A palmitate (150,000 U/kg) were inoculated with either the Moloney strain of murine sarcoma virus (M-MuSV) or poxvirus. Central body temperature was measured daily. Both viruses elicited fevers, but the fevers were less pronounced and of shorter duration in the mice ingesting the vitamin A-supplemented diet. Palpable M-MuSV-induced tumors appeared later, were less frequent, grew more slowly, and were resorbed sooner in the mice fed the vitamin A supplement. Similarly, in these mice the appearance of pox lesions was delayed, their numbers reduced, and their disappearance hastened.", "contents": "Antipyretic and antiviral action of vitamin A in Moloney sarcoma virus- and poxvirus-inoculated mice. Six week-old male CBA/J mice fed a commercial powdered laboratory chow or the same chow supplemented with vitamin A palmitate (150,000 U/kg) were inoculated with either the Moloney strain of murine sarcoma virus (M-MuSV) or poxvirus. Central body temperature was measured daily. Both viruses elicited fevers, but the fevers were less pronounced and of shorter duration in the mice ingesting the vitamin A-supplemented diet. Palpable M-MuSV-induced tumors appeared later, were less frequent, grew more slowly, and were resorbed sooner in the mice fed the vitamin A supplement. Similarly, in these mice the appearance of pox lesions was delayed, their numbers reduced, and their disappearance hastened."}
{"id": "PMID:187771", "title": "Feline leukemia virus infection: age-related variation in response of cats to experimental infection.", "content": "Sixty-seven specific-pathogen-free cats of various ages (newborn, 2 wk, 1 mo, 2 mo, 4 mo, and 1 yr) were inoculated ip with either the Rickard (R) or the Kawakami-Theilen (KT) strain of feline leukemia virus (FeLV). Susceptibility to FeLV was judged by induction of a) FeLV group-specific antigens (gsa) in leukocytes, b) FeLV-related disease, c) antibody to feline oncornavirus-associated cell membrane antigen (FOCMA), and d) virus-neutralizing (VN) antibody. Susceptibility to FeLV-decreased with age. Persistent viremia and FeLV-related disease developed in 100% of cats inoculated as newborns, in 85% of cats inoculated at 2 weeks to 2 months of age, and in 15% of cats inoculated at 4 months or 1 year of age. Cats susceptible to FeLV leukemogenesis became persistently FeLV gsa-positive (viremic) at 4 weeks post inoculation and thereafter and produced little or no FOCMA or VN antibody. Cats that resisted leukemogenesis by FeLV all developed persistent FOCMA and VN titers and never became FeLV gsa-positive. The disease in inoculated cats was influenced by virus strain; FeLV-R induced predominantly thymic lymphosarcoma, whereas FeLV-KT caused fatal nonregenerative anemia without concurrent neoplasia.", "contents": "Feline leukemia virus infection: age-related variation in response of cats to experimental infection. Sixty-seven specific-pathogen-free cats of various ages (newborn, 2 wk, 1 mo, 2 mo, 4 mo, and 1 yr) were inoculated ip with either the Rickard (R) or the Kawakami-Theilen (KT) strain of feline leukemia virus (FeLV). Susceptibility to FeLV was judged by induction of a) FeLV group-specific antigens (gsa) in leukocytes, b) FeLV-related disease, c) antibody to feline oncornavirus-associated cell membrane antigen (FOCMA), and d) virus-neutralizing (VN) antibody. Susceptibility to FeLV-decreased with age. Persistent viremia and FeLV-related disease developed in 100% of cats inoculated as newborns, in 85% of cats inoculated at 2 weeks to 2 months of age, and in 15% of cats inoculated at 4 months or 1 year of age. Cats susceptible to FeLV leukemogenesis became persistently FeLV gsa-positive (viremic) at 4 weeks post inoculation and thereafter and produced little or no FOCMA or VN antibody. Cats that resisted leukemogenesis by FeLV all developed persistent FOCMA and VN titers and never became FeLV gsa-positive. The disease in inoculated cats was influenced by virus strain; FeLV-R induced predominantly thymic lymphosarcoma, whereas FeLV-KT caused fatal nonregenerative anemia without concurrent neoplasia."}
{"id": "PMID:187772", "title": "Cylindroid lamella-particle complexes in lymphoma cells by northern pike (Esox lucius).", "content": "Cells of the malignant lymphoma of northern pike of Canada contained cylindrical structures with central cores of cytoplasmic elements and walls composed of lamellae in a spiral arrangement, separated by ribosome-like particles or by membranes. These cylindroids were similar, if not identical, to structures in the cells of certain human lymphomas and leukemias. In cross and longitudinal sections, the lamellae showed a pattern of light and dark bands resulting in an approximately 95 A-period that has not been described in the human cylindroids.", "contents": "Cylindroid lamella-particle complexes in lymphoma cells by northern pike (Esox lucius). Cells of the malignant lymphoma of northern pike of Canada contained cylindrical structures with central cores of cytoplasmic elements and walls composed of lamellae in a spiral arrangement, separated by ribosome-like particles or by membranes. These cylindroids were similar, if not identical, to structures in the cells of certain human lymphomas and leukemias. In cross and longitudinal sections, the lamellae showed a pattern of light and dark bands resulting in an approximately 95 A-period that has not been described in the human cylindroids."}
{"id": "PMID:187773", "title": "Transmission of murine leukemia virus (Scripps) from parent to progeny mice: a comparison of assay systems.", "content": "Transmission of murine leukemia virus (MuLV) from parent to progeny C3H/St and C57BL/St mice was examined by four assay systems: 1) recovery of infectious NB-tropic MuLV from spleen cultures, 2) the radioimmunoassay for p30 antigenemia, 3) morphologic examination for lymphoma development, and 4) the indirect fluorescent antibody technique for antinuclear antibodies (ANA). Transmission of MuLV (Scripps) occurred in 90-100% of C3H/St and C57BL/St progeny nursed by mothers with p30 antigenemia. All assays except ANA were equally sensitive for the determination of MuLV transmission in C3H/St mice, but the incidence of transmission in C57BL/St mice was determined only by assays of their cultured spleens for MuLV. Incidences of ANA were increased in all generations of C57BL/St mice compared with controls; the route of transmission of MuLV (Scripps) was not a factor. Only C3H/St mice infected by virus transmitted from parent to progeny developed ANA. Infectious MuLV was invariably recovered from spleens cultured from mice with p30 antigenemia, which was present in all mice that developed lymphoma. NB-tropic MuLV was also recovered after prolonged cultivation from spleens of 75% of C57BL/St progeny mice that did not develop p30 antigenemia. These suggested that MuLV (Scripps) could exist either as a productive persistent or nonproductive latent infection in C57BL/St mice.", "contents": "Transmission of murine leukemia virus (Scripps) from parent to progeny mice: a comparison of assay systems. Transmission of murine leukemia virus (MuLV) from parent to progeny C3H/St and C57BL/St mice was examined by four assay systems: 1) recovery of infectious NB-tropic MuLV from spleen cultures, 2) the radioimmunoassay for p30 antigenemia, 3) morphologic examination for lymphoma development, and 4) the indirect fluorescent antibody technique for antinuclear antibodies (ANA). Transmission of MuLV (Scripps) occurred in 90-100% of C3H/St and C57BL/St progeny nursed by mothers with p30 antigenemia. All assays except ANA were equally sensitive for the determination of MuLV transmission in C3H/St mice, but the incidence of transmission in C57BL/St mice was determined only by assays of their cultured spleens for MuLV. Incidences of ANA were increased in all generations of C57BL/St mice compared with controls; the route of transmission of MuLV (Scripps) was not a factor. Only C3H/St mice infected by virus transmitted from parent to progeny developed ANA. Infectious MuLV was invariably recovered from spleens cultured from mice with p30 antigenemia, which was present in all mice that developed lymphoma. NB-tropic MuLV was also recovered after prolonged cultivation from spleens of 75% of C57BL/St progeny mice that did not develop p30 antigenemia. These suggested that MuLV (Scripps) could exist either as a productive persistent or nonproductive latent infection in C57BL/St mice."}
{"id": "PMID:187774", "title": "Two-way selection of a stock of Swiss albino mice for mammary tumorigenesis: establishment of two new strains (SHN and SLN).", "content": "Two mouse strains (SHN and SLN) with high and low incidences, respectively, of mammary tumors were established from the same basal stock of Swiss albino mice that were unrelated in origin to other mouse  strains with mammary tumors.  In the breeders, mammary tumor incidence and average age of the mice when they developed mammary tumors were 97.2 % and 6.6 months for SHN, and 5.57% and 10.1 months for SLN, respectively...", "contents": "Two-way selection of a stock of Swiss albino mice for mammary tumorigenesis: establishment of two new strains (SHN and SLN). Two mouse strains (SHN and SLN) with high and low incidences, respectively, of mammary tumors were established from the same basal stock of Swiss albino mice that were unrelated in origin to other mouse  strains with mammary tumors.  In the breeders, mammary tumor incidence and average age of the mice when they developed mammary tumors were 97.2 % and 6.6 months for SHN, and 5.57% and 10.1 months for SLN, respectively..."}
{"id": "PMID:187775", "title": "In vitro susceptibility of mink lung cells to the mouse mammary tumor virus.", "content": "Lung cells from mink embryos were infected in vitro with a purified mammary tumor virus isolated from RIII mouse milk. Specific virus antigen at the cell surface was detected by membrane immunofluorescence; B-type virions budding from the cell membrane were seen by electron microscopy. Nucleic acid hybridization confirmed replication and specificity of the virus produced.", "contents": "In vitro susceptibility of mink lung cells to the mouse mammary tumor virus. Lung cells from mink embryos were infected in vitro with a purified mammary tumor virus isolated from RIII mouse milk. Specific virus antigen at the cell surface was detected by membrane immunofluorescence; B-type virions budding from the cell membrane were seen by electron microscopy. Nucleic acid hybridization confirmed replication and specificity of the virus produced."}
{"id": "PMID:187776", "title": "Evaluation of Moloney murine sarcoma and leukemia virus complex as a model for airborne oncogenic virus biohazards: survival of airborne virus and exposure of mice.", "content": "Aerosols of the Moloney murine sarcoma virus (MuSV-M) and leukemia virus (MuLV-M) complex (MuSV-M/MuLV-M) were generated from refluxing atomizers and then aged in rotating drums at 21 degrees C holding temperature with relative humidities ranging from 25 to 76%. The MuSV-M and MuLV-M aerosolized from the same tumor extract preparation survived almost equally at the four humidity levels. Both viruses remained viable in the airborne state for at least 2 hours after aerosolization. When mice were exposed to airborne MuSV-M/MuLV-M, no macroscopic lesions were observed in lungs or other tissues examined during the 2-month postexposure period. On the basis of this study, MuSV-M was determined unsuitable as a \"model system\" in which a simple aerosol dose response could be used for biohazard evaluation of oncogenic virus aerosols.", "contents": "Evaluation of Moloney murine sarcoma and leukemia virus complex as a model for airborne oncogenic virus biohazards: survival of airborne virus and exposure of mice. Aerosols of the Moloney murine sarcoma virus (MuSV-M) and leukemia virus (MuLV-M) complex (MuSV-M/MuLV-M) were generated from refluxing atomizers and then aged in rotating drums at 21 degrees C holding temperature with relative humidities ranging from 25 to 76%. The MuSV-M and MuLV-M aerosolized from the same tumor extract preparation survived almost equally at the four humidity levels. Both viruses remained viable in the airborne state for at least 2 hours after aerosolization. When mice were exposed to airborne MuSV-M/MuLV-M, no macroscopic lesions were observed in lungs or other tissues examined during the 2-month postexposure period. On the basis of this study, MuSV-M was determined unsuitable as a \"model system\" in which a simple aerosol dose response could be used for biohazard evaluation of oncogenic virus aerosols."}
{"id": "PMID:187777", "title": "Adenocarcinoma of the kidney. II. Enzyme histochemistry of renal adenocarcinomas induced in rats by N-(4'-fluoro-4-biphenylyl)acetamide.", "content": "Activities of a broad spectrum of enzymes were studied histochemically in renal adenocarcinomas induced in young male F344 rats by chronic dietary administration of the carcinogen N(4'-fluoro-4-biphenylyl)acetamide. Enzymes included were: dehydrogenases of glucose-6-phosphate, lactate, succinate, malate, and alpha-glycerophosphate; peroxidase (catalase); glucose-6-phosphatase; alkaline and acid phosphatase; Mg2+ ATPase; 5'-nucleotidase; and aminopeptidase. Levels of enzyme activity were estimated visually and scored from 0 (not detectable) to a maximum of 5 (intense). Comparison of estimated activity for each enzyme was made between small neoplastic nodules (stage III tumors) and large adenocarcinomas (stage IV tumors) and between tumors and portions of normal proximal tubules in parenchyma of kidneys from untreated control rats. The results, which revealed nearly identical levels of activity for most enzymes in both stages III and IV tumors, suggested similar metabolic and biologic behavior of these lesions. However, when data for tumors were compared with data for normal proximal tubules, striking differences were observed consistent with: 1) a marked shift of energy metabolism from oxidative to glycolytic production of ATP, with a corresponding reduction in mitochondrial respiration; and 2) simplification of plasma membrane specializations that were possibly associated with a reduction or loss of transport function. These findings were compared with other histochemical, biochemical, and ultrastructural studies of renal adenocarcinomas in rats and man.", "contents": "Adenocarcinoma of the kidney. II. Enzyme histochemistry of renal adenocarcinomas induced in rats by N-(4'-fluoro-4-biphenylyl)acetamide. Activities of a broad spectrum of enzymes were studied histochemically in renal adenocarcinomas induced in young male F344 rats by chronic dietary administration of the carcinogen N(4'-fluoro-4-biphenylyl)acetamide. Enzymes included were: dehydrogenases of glucose-6-phosphate, lactate, succinate, malate, and alpha-glycerophosphate; peroxidase (catalase); glucose-6-phosphatase; alkaline and acid phosphatase; Mg2+ ATPase; 5'-nucleotidase; and aminopeptidase. Levels of enzyme activity were estimated visually and scored from 0 (not detectable) to a maximum of 5 (intense). Comparison of estimated activity for each enzyme was made between small neoplastic nodules (stage III tumors) and large adenocarcinomas (stage IV tumors) and between tumors and portions of normal proximal tubules in parenchyma of kidneys from untreated control rats. The results, which revealed nearly identical levels of activity for most enzymes in both stages III and IV tumors, suggested similar metabolic and biologic behavior of these lesions. However, when data for tumors were compared with data for normal proximal tubules, striking differences were observed consistent with: 1) a marked shift of energy metabolism from oxidative to glycolytic production of ATP, with a corresponding reduction in mitochondrial respiration; and 2) simplification of plasma membrane specializations that were possibly associated with a reduction or loss of transport function. These findings were compared with other histochemical, biochemical, and ultrastructural studies of renal adenocarcinomas in rats and man."}
{"id": "PMID:187778", "title": "Suppression of tumor growth in strain 2 guinea pigs by xenogeneic antitumor antibody.", "content": "Line 10 hepatoma cells were incubated with antiserum specific against line 10 cells (RaL10) and then tested for growth in syngeneic Wright strain 2 guinea pigs. Palpable tumors appeared in only 11 of 23 animals inoculated id with 10(5) RaL10-treated tumor cells, compared with an incidence of 21 of 23 for nonimmune rabbit serum (NRS)-treated cells and 23 of 23 for cells treated with syngeneic guinea pig serum. Animals inoculated with RaL10-treated tumor cells did not develop systemic tumor immunity. The long-term survival of guinea pigs receiving RaL10-treated tumor cells iv was 6 of 12 with a dose of 10(5) cells and 8 of 11 with 10(4) cells. None of the animals receiving 10(4) or 10(5) control tumor cells treated with NRS survived. RaL10 antiserum was not toxic to line 10 tumor cells in vitro, but mediated tumor-specific cytolytic reactions in the presence of fresh guinea pig serum or on the addition of peritoneal exudate cells from nonimmunized syngeneic guinea pigs.", "contents": "Suppression of tumor growth in strain 2 guinea pigs by xenogeneic antitumor antibody. Line 10 hepatoma cells were incubated with antiserum specific against line 10 cells (RaL10) and then tested for growth in syngeneic Wright strain 2 guinea pigs. Palpable tumors appeared in only 11 of 23 animals inoculated id with 10(5) RaL10-treated tumor cells, compared with an incidence of 21 of 23 for nonimmune rabbit serum (NRS)-treated cells and 23 of 23 for cells treated with syngeneic guinea pig serum. Animals inoculated with RaL10-treated tumor cells did not develop systemic tumor immunity. The long-term survival of guinea pigs receiving RaL10-treated tumor cells iv was 6 of 12 with a dose of 10(5) cells and 8 of 11 with 10(4) cells. None of the animals receiving 10(4) or 10(5) control tumor cells treated with NRS survived. RaL10 antiserum was not toxic to line 10 tumor cells in vitro, but mediated tumor-specific cytolytic reactions in the presence of fresh guinea pig serum or on the addition of peritoneal exudate cells from nonimmunized syngeneic guinea pigs."}
{"id": "PMID:187779", "title": "Characteristics of JMV Marek's disease tumor: a nonproductively infected transplantable cell lacking in rescuable Virus.", "content": "Cells of the JMV Marek's disease (MD) tumor, originally produced by rapid serial passage of MD lymphoma cells in chickens, were characterized to determine whether they were of host or donor origin and to ascertain certain virus-host cell interrelationships. Differences noted in blood group B surface alloantigens between tumor cells and host lymphocytes indicated a probable nonhost origin (i.e., transplantability) of the tumor. JMV spleen tumors contained predominantly large lymphoblasts bearing MD tumor-associated surface antigen. DNA from JMV tumor cell suspensions hybridized significantly with MD virus cRNA, which indicated that JMV cells contained at least a portion of the MD virus genome. No MD virus was rescued from JMV tumors by techniques suitable for rescue of virus from MD lymphomas. The JMV tumor cells were also devoid of MD virus-specific antigens. These properties differed markedly from those of MD lymphoma cells and make the JMV tumor cell a unique, potentially valuable, tool for further study of oncogenic herpesvirus infection and tumor immunity in the chicken.", "contents": "Characteristics of JMV Marek's disease tumor: a nonproductively infected transplantable cell lacking in rescuable Virus. Cells of the JMV Marek's disease (MD) tumor, originally produced by rapid serial passage of MD lymphoma cells in chickens, were characterized to determine whether they were of host or donor origin and to ascertain certain virus-host cell interrelationships. Differences noted in blood group B surface alloantigens between tumor cells and host lymphocytes indicated a probable nonhost origin (i.e., transplantability) of the tumor. JMV spleen tumors contained predominantly large lymphoblasts bearing MD tumor-associated surface antigen. DNA from JMV tumor cell suspensions hybridized significantly with MD virus cRNA, which indicated that JMV cells contained at least a portion of the MD virus genome. No MD virus was rescued from JMV tumors by techniques suitable for rescue of virus from MD lymphomas. The JMV tumor cells were also devoid of MD virus-specific antigens. These properties differed markedly from those of MD lymphoma cells and make the JMV tumor cell a unique, potentially valuable, tool for further study of oncogenic herpesvirus infection and tumor immunity in the chicken."}
{"id": "PMID:187780", "title": "Biologic characteristics of some mouse mammary tumor viruses.", "content": "The mammary tumor virus (MuMTV) in the milks of 7 mouse strains and substrains was titrated for infectivity in 4 strains. The data indicated that: 1) Each strain shed a different MuMTV and some genetic strains carried two MuMTV's, each discernible by its mouse strain preference in infectivity tests. 2) Less than 5% of RIIIf and about 10% of Af mice shed detectable MuMTV antigen in their milks after the third parturition. After the sixth parturition, 33% of RIIIf and 50% of Af, and after the ninth parturition, 60% of RIIIf and 90% of Af mice shed viral antigen in their milks. The MuMTV's in milks of high-parity mothers were most infectious in mouse strains different from those most susceptible to MuMTV in RIII and A milks of low-parity mothers. Therefore, RIII and A mice each harbored two viruses, one that was removed by foster-nursing and the other that was not. 3) The susceptibility incidence of RIIIfC57BL mice to RIII virus changed gradually from about 10% in 1970 to about 70% in 1975. Susceptibility of C57BL mice to RIII virus did not change appreciably over this period, and the natural tumor incidence in RIIIfC57BL remained unchanged (about 10%). In addition to their susceptibility to RIII virus, C57BL mice were also susceptible to GR virus; they were relatively resistant to other strains tested. They were especially resistant to RIIIf virus, to which Af and BALB/c mice were very susceptible. 4) Approximately 90% of C3HfC57BL and C3HfBALB/c mice shed antigen in their milks after the third parturition, although the tumor incidence was less and occurred later than in C3H mice. No clear-cut differences could be detected in infectivities between low-parity C3H milk and high-parity C3Hf milks tested in several assay strains.", "contents": "Biologic characteristics of some mouse mammary tumor viruses. The mammary tumor virus (MuMTV) in the milks of 7 mouse strains and substrains was titrated for infectivity in 4 strains. The data indicated that: 1) Each strain shed a different MuMTV and some genetic strains carried two MuMTV's, each discernible by its mouse strain preference in infectivity tests. 2) Less than 5% of RIIIf and about 10% of Af mice shed detectable MuMTV antigen in their milks after the third parturition. After the sixth parturition, 33% of RIIIf and 50% of Af, and after the ninth parturition, 60% of RIIIf and 90% of Af mice shed viral antigen in their milks. The MuMTV's in milks of high-parity mothers were most infectious in mouse strains different from those most susceptible to MuMTV in RIII and A milks of low-parity mothers. Therefore, RIII and A mice each harbored two viruses, one that was removed by foster-nursing and the other that was not. 3) The susceptibility incidence of RIIIfC57BL mice to RIII virus changed gradually from about 10% in 1970 to about 70% in 1975. Susceptibility of C57BL mice to RIII virus did not change appreciably over this period, and the natural tumor incidence in RIIIfC57BL remained unchanged (about 10%). In addition to their susceptibility to RIII virus, C57BL mice were also susceptible to GR virus; they were relatively resistant to other strains tested. They were especially resistant to RIIIf virus, to which Af and BALB/c mice were very susceptible. 4) Approximately 90% of C3HfC57BL and C3HfBALB/c mice shed antigen in their milks after the third parturition, although the tumor incidence was less and occurred later than in C3H mice. No clear-cut differences could be detected in infectivities between low-parity C3H milk and high-parity C3Hf milks tested in several assay strains."}
{"id": "PMID:187781", "title": "Characterization of feline T-and B-lymphocytes and identification of an experimentally induced T-cell neoplasm in the cat.", "content": "Membrane markers of feline T- and B-lymphocytes were identified for further investigation of leukemogenesis in the cat. Feline T-cells formed spontaneous erythrocyte rosettes with guinea pig (GPE) and rat erythrocytes (RE). The receptors for GPE and RE were separate entities and expressed independently on lymphoid cell membranes. The RE receptor appeared to be present only on more mature or differentiated T-cells, whereas the GPE receptor reacted with a broader population that included less differentiated T-cells. Feline B-cells bore a complement receptor that was detected by adherence of SE coated with antibody and complement. Malignant lymphoblasts obtained from thoracic fluid of cats with feline leukemia virus (FeLV)-induced thymic lymphosarcomas, as well as FL-74 cells (a FeLV-transformed feline lymphoblastoid cell line) expressed T-cell markers. These results provided definitive evidence for markers of feline T- and B-cells and identified an experimentally induced T-cell lymphosarcoma.", "contents": "Characterization of feline T-and B-lymphocytes and identification of an experimentally induced T-cell neoplasm in the cat. Membrane markers of feline T- and B-lymphocytes were identified for further investigation of leukemogenesis in the cat. Feline T-cells formed spontaneous erythrocyte rosettes with guinea pig (GPE) and rat erythrocytes (RE). The receptors for GPE and RE were separate entities and expressed independently on lymphoid cell membranes. The RE receptor appeared to be present only on more mature or differentiated T-cells, whereas the GPE receptor reacted with a broader population that included less differentiated T-cells. Feline B-cells bore a complement receptor that was detected by adherence of SE coated with antibody and complement. Malignant lymphoblasts obtained from thoracic fluid of cats with feline leukemia virus (FeLV)-induced thymic lymphosarcomas, as well as FL-74 cells (a FeLV-transformed feline lymphoblastoid cell line) expressed T-cell markers. These results provided definitive evidence for markers of feline T- and B-cells and identified an experimentally induced T-cell lymphosarcoma."}
{"id": "PMID:187782", "title": "Fine structure of pancreatic adenocarcinoma induced in rats by 7,12-dimethylbenz(a)anthracene.", "content": "We induced pancreatic adenocarcinomas in Long-Evans rats by placing crystals, 2-3 mg, of 7,12-dimethylbenz[a]anthracene (DMBA) in a 2- to 3-mm incision in the \"head\" of the pancreas approximately 1 cm from the duodenum. The incisions were closed with one or two silk sutures. The animals were killed 4-10 months after DMBA implantation, and nodules were removed and routinely prepared for light and/or electron microscopic study. Histologic organization varied from normal, through areas of tubule-like structures, to sheets of pleomorphic tumor cells. Electron microscopic study of tumor cells revealed large electron-lucent nuclei that frequently had irregular outlines and prominent nucleoli. The predominant feature of the cytoplasm was abundant rough endoplasmic reticulum. Zymogen granules were rare. Adjacent cells sometimes were jointed by an apical junctional complex to form a lumen into which projected irregular microvilli. A basal lamina sometimes occurred at the bases of the tumor cells. The fine structural similarity of these tumor cells to acinar cells was noted.", "contents": "Fine structure of pancreatic adenocarcinoma induced in rats by 7,12-dimethylbenz(a)anthracene. We induced pancreatic adenocarcinomas in Long-Evans rats by placing crystals, 2-3 mg, of 7,12-dimethylbenz[a]anthracene (DMBA) in a 2- to 3-mm incision in the \"head\" of the pancreas approximately 1 cm from the duodenum. The incisions were closed with one or two silk sutures. The animals were killed 4-10 months after DMBA implantation, and nodules were removed and routinely prepared for light and/or electron microscopic study. Histologic organization varied from normal, through areas of tubule-like structures, to sheets of pleomorphic tumor cells. Electron microscopic study of tumor cells revealed large electron-lucent nuclei that frequently had irregular outlines and prominent nucleoli. The predominant feature of the cytoplasm was abundant rough endoplasmic reticulum. Zymogen granules were rare. Adjacent cells sometimes were jointed by an apical junctional complex to form a lumen into which projected irregular microvilli. A basal lamina sometimes occurred at the bases of the tumor cells. The fine structural similarity of these tumor cells to acinar cells was noted."}
{"id": "PMID:187783", "title": "Oncornavirus particles in lymphoid cultures from a howler monkey with Herpesvirus saimiri-induced disease.", "content": "Budding and extracellular oncornavirus particles were observed in cells of lymphoid cultures derived from the spleen, lymph node, and blood of a howler monkey (Alouatta caraya) that developed a malignant lymphoproliferative disease after infection with Herpesvirus saimiri. The various possible sources of origin of these particles are discussed.", "contents": "Oncornavirus particles in lymphoid cultures from a howler monkey with Herpesvirus saimiri-induced disease. Budding and extracellular oncornavirus particles were observed in cells of lymphoid cultures derived from the spleen, lymph node, and blood of a howler monkey (Alouatta caraya) that developed a malignant lymphoproliferative disease after infection with Herpesvirus saimiri. The various possible sources of origin of these particles are discussed."}
{"id": "PMID:187784", "title": "Mononuclear cell fraction carrying Herpesvirus saimiri in persistently infected squirrel monkeys.", "content": "Circulating lymphocytes from squirrel monkeys persistently infected with Herpesvirus saimiri (HVS) were separated into B- and T-lymphocyte fractions by a rosette-enrichment technique. HVS was isolated only from lymphocyte fractions forming rosettes or from unseparated lymphocytes; this indicated that T-lymphocytes were the target cells for HVS in the natural host, squirrel monkeys.", "contents": "Mononuclear cell fraction carrying Herpesvirus saimiri in persistently infected squirrel monkeys. Circulating lymphocytes from squirrel monkeys persistently infected with Herpesvirus saimiri (HVS) were separated into B- and T-lymphocyte fractions by a rosette-enrichment technique. HVS was isolated only from lymphocyte fractions forming rosettes or from unseparated lymphocytes; this indicated that T-lymphocytes were the target cells for HVS in the natural host, squirrel monkeys."}
{"id": "PMID:187785", "title": "Immunotherapy of cancer with nonliving mycobacteria and cord factor (trehalose-6,6'-dimycolate) in aqueous medium.", "content": "Heat-killed BCG, cord factor (trehalose-6,6'-dimycolate), or killed BCG plus cord factor in aqueous medium, admixed with tumor cells and injected into the skin of guinea pigs, inhibited the growth of a hepatocellular carcinoma. Intralesional administration of killed BCG or Mycobacterium kansasii coated with cord factor, in the same medium, caused regression of established tumors in 48 and 45% of the treated animals, respectively.", "contents": "Immunotherapy of cancer with nonliving mycobacteria and cord factor (trehalose-6,6'-dimycolate) in aqueous medium. Heat-killed BCG, cord factor (trehalose-6,6'-dimycolate), or killed BCG plus cord factor in aqueous medium, admixed with tumor cells and injected into the skin of guinea pigs, inhibited the growth of a hepatocellular carcinoma. Intralesional administration of killed BCG or Mycobacterium kansasii coated with cord factor, in the same medium, caused regression of established tumors in 48 and 45% of the treated animals, respectively."}
{"id": "PMID:187786", "title": "Ascites form of a human cancer serially transplantable in nude mice.", "content": "Human adenocarcinoma cells injected into the peritoneal cavities of BALB/c nude mice (nu/nu) induced ascites carcinoma. The inoculant was obtained from subcutaneous tumors produced in nude mice by an injection of ascites cells from a patient with carcinomatous peritonitis caused by mucinous adenocarcinoma of the stomach. An ascitic fluid began to accumulate 45 days after inoculation and reached the maximum volume within 120 days. Dispersed stomach cancer cells in the ascites could be serially transplanted in nude mice in an ascites form. The morphology of these cells was similar to that of the original cells in the ascitic fluid of a patient with carcinomatous peritonitis.", "contents": "Ascites form of a human cancer serially transplantable in nude mice. Human adenocarcinoma cells injected into the peritoneal cavities of BALB/c nude mice (nu/nu) induced ascites carcinoma. The inoculant was obtained from subcutaneous tumors produced in nude mice by an injection of ascites cells from a patient with carcinomatous peritonitis caused by mucinous adenocarcinoma of the stomach. An ascitic fluid began to accumulate 45 days after inoculation and reached the maximum volume within 120 days. Dispersed stomach cancer cells in the ascites could be serially transplanted in nude mice in an ascites form. The morphology of these cells was similar to that of the original cells in the ascitic fluid of a patient with carcinomatous peritonitis."}
{"id": "PMID:187787", "title": "Burkitt's lymphoma: its clinical course in relation to immunologic reactivities to Epstein-Barr virus and tumor-related antigens.", "content": "In 141 patients with African Burkitt's lymphoma, the relationship between Epstein-Barr virus (EBV)-related antibody titers and the clinical course of this disease was presented. Antiviral capsid antigen tests gave positive results in all patients, siblings, and control neighbors; but the geometric mean antibody titers to viral capsid antigen were significantly higher in patients than in siblings or neighbors (P less than 0.001). No control neighbors or siblings had antibodies to restricted (EA-R) or diffuse (EA-D) early antigen. Mean geometric anti-EA-R titers at admssion and at last visit were significantly lower in patients with stage (I and II) than in those with stage (III and IV) disease; this most likely reflected the degree of tumor burden. Patients who relapsed after 1 year of sustained remission had significantly higher anti-EA-R titers than did those who did not. The increase in the probability of relapse was sixfold for those patients with an anti-EA-R titer of greater than 160 after 1 year of sustained remission. Survivors and nonsurvivors differed significantly in the final EA-R and Epstein-Barr virus nuclear antigen (EBNA) titers (P less than 0.05 and P less than 0.001, respectively). Anti-EA-D titers were particularly likely to be positive in patients with multiple relapses. When skin reactivity to an antigen from RAJI cells was compared to EBV-related serologic reactions in the same patient, a significant inverse correlation (P less than 0.001) between skin reactivity and EBNA titers appeared. Pretreatment sera from patients with high EBNA titers did not block skin reactivity to the RAJI antigen.", "contents": "Burkitt's lymphoma: its clinical course in relation to immunologic reactivities to Epstein-Barr virus and tumor-related antigens. In 141 patients with African Burkitt's lymphoma, the relationship between Epstein-Barr virus (EBV)-related antibody titers and the clinical course of this disease was presented. Antiviral capsid antigen tests gave positive results in all patients, siblings, and control neighbors; but the geometric mean antibody titers to viral capsid antigen were significantly higher in patients than in siblings or neighbors (P less than 0.001). No control neighbors or siblings had antibodies to restricted (EA-R) or diffuse (EA-D) early antigen. Mean geometric anti-EA-R titers at admssion and at last visit were significantly lower in patients with stage (I and II) than in those with stage (III and IV) disease; this most likely reflected the degree of tumor burden. Patients who relapsed after 1 year of sustained remission had significantly higher anti-EA-R titers than did those who did not. The increase in the probability of relapse was sixfold for those patients with an anti-EA-R titer of greater than 160 after 1 year of sustained remission. Survivors and nonsurvivors differed significantly in the final EA-R and Epstein-Barr virus nuclear antigen (EBNA) titers (P less than 0.05 and P less than 0.001, respectively). Anti-EA-D titers were particularly likely to be positive in patients with multiple relapses. When skin reactivity to an antigen from RAJI cells was compared to EBV-related serologic reactions in the same patient, a significant inverse correlation (P less than 0.001) between skin reactivity and EBNA titers appeared. Pretreatment sera from patients with high EBNA titers did not block skin reactivity to the RAJI antigen."}
{"id": "PMID:187788", "title": "Long-term effects of neonatal steroid exposure on mammary gland development and tumorigenesis in mice.", "content": "Newborn female mice of three strains--BALB/cfC3H [mammary tumor virus (MuMTV)-infected], BALB/c, and C57BL (both virus-free)--were given injections of 17beta-estradiol or testosterone, alone or in combination with ovine prolactin, for the first 5 days of life. Half of each group of mice were ovariectomized at 40 days of age, and all mice were killed between 6 and 16 months of age. Mammary glands of BALB/cfC3H mice receiving steroid hormones were better developed than those of mice not receiving steroids. Androgen induced a higher incidence of grossly dilated ducts and secretion-filled alveoli. Mammary nodule and tumor incidences were higher in steroid-treated mice than in controls; androgen resulted in higher incidences than did estrogen. The age of onset of mammary tumors was also earlier after neonatal steroid treatment. In BALB/c mice, neonatal injections of estrogen induced some alveolar development of the mammary gland; neonatal injections of ovine prolactin had a greater effect. The mammary glands of C57BL mice did not show any evidence of stimulation by neonatal hormone treatment, which indicated the probability of strain differences. However, no nodules or tumors occurred in these MuMTV-free strains. Therefore, MuMTV was essential for neoplastic mammary responses to neonatal hormone treatment. Ovariectomy prevented alveolar development and abnormal changes in the mammary glands of all groups, thus indicating that ovary-independent alterations in the mammary gland were not induced by neonatal steroid treatment. We concluded that neonatal steroid exposure resulted in increased mammary tumor risk in mice, but only in the presence of both MuMTV and ovaries.", "contents": "Long-term effects of neonatal steroid exposure on mammary gland development and tumorigenesis in mice. Newborn female mice of three strains--BALB/cfC3H [mammary tumor virus (MuMTV)-infected], BALB/c, and C57BL (both virus-free)--were given injections of 17beta-estradiol or testosterone, alone or in combination with ovine prolactin, for the first 5 days of life. Half of each group of mice were ovariectomized at 40 days of age, and all mice were killed between 6 and 16 months of age. Mammary glands of BALB/cfC3H mice receiving steroid hormones were better developed than those of mice not receiving steroids. Androgen induced a higher incidence of grossly dilated ducts and secretion-filled alveoli. Mammary nodule and tumor incidences were higher in steroid-treated mice than in controls; androgen resulted in higher incidences than did estrogen. The age of onset of mammary tumors was also earlier after neonatal steroid treatment. In BALB/c mice, neonatal injections of estrogen induced some alveolar development of the mammary gland; neonatal injections of ovine prolactin had a greater effect. The mammary glands of C57BL mice did not show any evidence of stimulation by neonatal hormone treatment, which indicated the probability of strain differences. However, no nodules or tumors occurred in these MuMTV-free strains. Therefore, MuMTV was essential for neoplastic mammary responses to neonatal hormone treatment. Ovariectomy prevented alveolar development and abnormal changes in the mammary glands of all groups, thus indicating that ovary-independent alterations in the mammary gland were not induced by neonatal steroid treatment. We concluded that neonatal steroid exposure resulted in increased mammary tumor risk in mice, but only in the presence of both MuMTV and ovaries."}
{"id": "PMID:187789", "title": "Induction of lymphoma and associated xenotropic type C virus in C57L mice by whole-body irradiation.", "content": "Adult C57L mice received sublethal whole-body X-irradiation. Between 3 and 11 months later, 5 of the 7 exposed mice developed histopathologically confirmed malignant lymphomas (lymphocytic type) that primarily involved the thymus. The lymphomas were readily transplantable to other C57L mice of any age, which developed fetal lymphomatous involvement; the tumor cells could also be propagated in tissue culture. A xenotropic murine type C virus (MuX) was isolated from the cultured lymphoma cells after cocultivation with a permissive dog line. MuX activity was demonstrated by electron microscopy, complement fixation, indirect fluorescent antibody, infectivity, and genome rescue.", "contents": "Induction of lymphoma and associated xenotropic type C virus in C57L mice by whole-body irradiation. Adult C57L mice received sublethal whole-body X-irradiation. Between 3 and 11 months later, 5 of the 7 exposed mice developed histopathologically confirmed malignant lymphomas (lymphocytic type) that primarily involved the thymus. The lymphomas were readily transplantable to other C57L mice of any age, which developed fetal lymphomatous involvement; the tumor cells could also be propagated in tissue culture. A xenotropic murine type C virus (MuX) was isolated from the cultured lymphoma cells after cocultivation with a permissive dog line. MuX activity was demonstrated by electron microscopy, complement fixation, indirect fluorescent antibody, infectivity, and genome rescue."}
{"id": "PMID:187790", "title": "Lymphocyte mitogen reactivity and enumeration of circulating B- and T-cells during feline leukemia virus infection in the cat.", "content": "Mitogen-induced blast transformation of peripheral blood lymphocytes and quantitative changes in circulating T- and B-cells were studied serially in cats inoculated with feline leukemia virus (FeLV). Concanavalin A-induced blast transformation sharply declined beginning at 5 weeks post inoculation (Pl) in FeLV-infected cats when compared to age-matched uninfected control cats. Similar but less consistent changes were seen in responses to pokeweed mitogen-induced stimulation. In most infected kittens this defect persisted until they died from thymic lymphosarcoma, 15-24 weeks Pl. An early lymphopenia, due primarily to a decrease in circulating B-cells, occurred in infected cats 5-8 weeks Pl. Following a return of total and B-lymphocytes to control values, infected cats developed increased numbers of T-cells at 16 or more weeks Pl, which correlated with circulating lymphoblastic lymphocytes bearing T-cell markers. These results correlated neoplasia arising in a thymus-derived lymphocyte population with mitogenic hyporeactivity in the preneoplastic period and suggested that FeLV-induced immune alterations may be a necessary antecedent of leukemogenesis in the cat.", "contents": "Lymphocyte mitogen reactivity and enumeration of circulating B- and T-cells during feline leukemia virus infection in the cat. Mitogen-induced blast transformation of peripheral blood lymphocytes and quantitative changes in circulating T- and B-cells were studied serially in cats inoculated with feline leukemia virus (FeLV). Concanavalin A-induced blast transformation sharply declined beginning at 5 weeks post inoculation (Pl) in FeLV-infected cats when compared to age-matched uninfected control cats. Similar but less consistent changes were seen in responses to pokeweed mitogen-induced stimulation. In most infected kittens this defect persisted until they died from thymic lymphosarcoma, 15-24 weeks Pl. An early lymphopenia, due primarily to a decrease in circulating B-cells, occurred in infected cats 5-8 weeks Pl. Following a return of total and B-lymphocytes to control values, infected cats developed increased numbers of T-cells at 16 or more weeks Pl, which correlated with circulating lymphoblastic lymphocytes bearing T-cell markers. These results correlated neoplasia arising in a thymus-derived lymphocyte population with mitogenic hyporeactivity in the preneoplastic period and suggested that FeLV-induced immune alterations may be a necessary antecedent of leukemogenesis in the cat."}
{"id": "PMID:187791", "title": "Epithelial characteristics of tumor cells in nasophasyngeal carcinoma.", "content": "Electron microscopy examination of nasopharyngeal carcinoma grafts in nude mice showed that the tumor cells retained their epithelial characteristics, as betrayed by the presence of keratin fibrils and of functional complexes at the cell membrane. Thus the cells positive for Epstein-Barr virus-specific nuclear antigen present in such grafts do represent the progeny of human epithelial tumor cells. C-type virus particles were observed in one tumor graft, indicating that epithelial human cells could pick up a mouse virus.", "contents": "Epithelial characteristics of tumor cells in nasophasyngeal carcinoma. Electron microscopy examination of nasopharyngeal carcinoma grafts in nude mice showed that the tumor cells retained their epithelial characteristics, as betrayed by the presence of keratin fibrils and of functional complexes at the cell membrane. Thus the cells positive for Epstein-Barr virus-specific nuclear antigen present in such grafts do represent the progeny of human epithelial tumor cells. C-type virus particles were observed in one tumor graft, indicating that epithelial human cells could pick up a mouse virus."}
{"id": "PMID:187792", "title": "Membranes of normal hamster lymphocytes and lymphoid cells neoplastically transformed by simian virus 40. I. High-yield purification of plasma membrane fragments.", "content": "In this first paper of a series comparing the membranes of normal lymphocyte populations from male outbred Syrian hamsters with those of neoplastic transformants (GD 248) induced by simian virus 40, a method is described for the isolation of representative plasma membrane (PM) fragments from both cell types. Multiple criteria were used to monitor the purity and yield of PM material after cell disruption by nitrogen cavitation and after membrane fractionation by a combination of differential centrifugation and isopyknic ultracentrifugation in dextran density gradients. Lactoperoxidase-catalyzed radioiodination before cell disruption was used as an extrinsic surface marker; Na+,K+-activated ATPase, as well as alkaline phosphatase, was used as intrinsic functional PM markers. The distribution of nuclei, mitochondria, lysosomes, and endoplasmic reticulum (ER) during fractionation was monitored by the measurement of DNA, succinate dehydrogenase and monoamine oxidase, beta-glucuronidase and glucose-6-phosphatase, and NADH:lipoamide oxidoreductase, respectively. According to the three PM markers employed, a 15- to 20-fold purification (over homogenate) and a PM yield of about 65% were obtained for both cell categories, with negligible contamination by DNA, mitochondria, lysosomes, and er. The procedure also allowed recovery of 60% of the mitochondria free of other cell elements.", "contents": "Membranes of normal hamster lymphocytes and lymphoid cells neoplastically transformed by simian virus 40. I. High-yield purification of plasma membrane fragments. In this first paper of a series comparing the membranes of normal lymphocyte populations from male outbred Syrian hamsters with those of neoplastic transformants (GD 248) induced by simian virus 40, a method is described for the isolation of representative plasma membrane (PM) fragments from both cell types. Multiple criteria were used to monitor the purity and yield of PM material after cell disruption by nitrogen cavitation and after membrane fractionation by a combination of differential centrifugation and isopyknic ultracentrifugation in dextran density gradients. Lactoperoxidase-catalyzed radioiodination before cell disruption was used as an extrinsic surface marker; Na+,K+-activated ATPase, as well as alkaline phosphatase, was used as intrinsic functional PM markers. The distribution of nuclei, mitochondria, lysosomes, and endoplasmic reticulum (ER) during fractionation was monitored by the measurement of DNA, succinate dehydrogenase and monoamine oxidase, beta-glucuronidase and glucose-6-phosphatase, and NADH:lipoamide oxidoreductase, respectively. According to the three PM markers employed, a 15- to 20-fold purification (over homogenate) and a PM yield of about 65% were obtained for both cell categories, with negligible contamination by DNA, mitochondria, lysosomes, and er. The procedure also allowed recovery of 60% of the mitochondria free of other cell elements."}
{"id": "PMID:187793", "title": "Membranes of normal hamster lymphocytes and lymphoid cells neoplastically transformed by simian virus 40. II. Plasma membrane proteins analyzed by dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional immune electrophoresis.", "content": "The plasma membrane proteins of lymphocyte populations from normal outbred Syrian hamsters were compared with those of a neoplastic transformant line (GD 248) induced by simian virus 40. Both quantitative and qualitative differences were observed. Gradient dodecyl sulfate-polyacrylamide gel electrophoresis revealed 12 major protein components in the membranes of both cell populations. Both membrane categories also contained small amounts of immunoglobulin. Compared with the membranes of the reference cell population, GD 248 membranes showed a 60% decrease of approximately 210,000 daltons of glycoprotein; a 10% reduction of about a 48,000-dalton band and virtually complete loss of a 15,000-dalton component concomitant with a 57% increase in a 52,000-dalton band; fusion to two subcomponents (mol wt approximately 250,000 daltons); and emergence of approximately 120,000 and 30,000 daltons glycoproteins. In addition, the relative mobility of an approximately 95,000-dalton component increased by roughly 0.02 U. Crossed immune electrophoresis in Trition X-100 with heterologous antiserum against GD 248 microsomal membranes revealed both a new component with a high level of electrophoretic mobility and intensification and additional heterogeneity in a strongly antigenic component with a low level of electrophoretic mobility. Crossed-line immune electrophoresis indicated that at least two antigens in the membranes of GD 248 cells lacked the membranes of the reference cell population.", "contents": "Membranes of normal hamster lymphocytes and lymphoid cells neoplastically transformed by simian virus 40. II. Plasma membrane proteins analyzed by dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional immune electrophoresis. The plasma membrane proteins of lymphocyte populations from normal outbred Syrian hamsters were compared with those of a neoplastic transformant line (GD 248) induced by simian virus 40. Both quantitative and qualitative differences were observed. Gradient dodecyl sulfate-polyacrylamide gel electrophoresis revealed 12 major protein components in the membranes of both cell populations. Both membrane categories also contained small amounts of immunoglobulin. Compared with the membranes of the reference cell population, GD 248 membranes showed a 60% decrease of approximately 210,000 daltons of glycoprotein; a 10% reduction of about a 48,000-dalton band and virtually complete loss of a 15,000-dalton component concomitant with a 57% increase in a 52,000-dalton band; fusion to two subcomponents (mol wt approximately 250,000 daltons); and emergence of approximately 120,000 and 30,000 daltons glycoproteins. In addition, the relative mobility of an approximately 95,000-dalton component increased by roughly 0.02 U. Crossed immune electrophoresis in Trition X-100 with heterologous antiserum against GD 248 microsomal membranes revealed both a new component with a high level of electrophoretic mobility and intensification and additional heterogeneity in a strongly antigenic component with a low level of electrophoretic mobility. Crossed-line immune electrophoresis indicated that at least two antigens in the membranes of GD 248 cells lacked the membranes of the reference cell population."}
{"id": "PMID:187794", "title": "A method for the control of lymphoid leukosis in chickens.", "content": "Lymphoid leukosis (LL) was eliminated from 3 inbred lines of White Leghorn chickens that were temporarily kept in isolation. The method of control was based on three elements: 1) From an infected flock we selected hens that produced LL virus-free eggs. Pooled extracts from groups of embryos were tested for vertical virus transmission by the nonproducer cell activation test. 2) Only eggs from dams that did not congenitally shed virus to their embryos were used to produce progeny. The offspring were reared in isolation for 2 months (at which time the age-related resistance against tumor formation had developed sufficiently). 3) The birds were subsequently inoculated im with 10(5) mean tissue culture infective doses of LL viruses of subgroups A and B and transferred to a conventional chicken house. The controlled exposure provided immunity against LL virus infection in a highly infect environment. This procedure resulted in birds a) with no boservable LL, and b) producing LL virus-free eggs. To obtain flocks that had no LL and produced virus-free progeny, the procedure had to be repeated for at least two generations due to the intermittent virus excretion that often occurred.", "contents": "A method for the control of lymphoid leukosis in chickens. Lymphoid leukosis (LL) was eliminated from 3 inbred lines of White Leghorn chickens that were temporarily kept in isolation. The method of control was based on three elements: 1) From an infected flock we selected hens that produced LL virus-free eggs. Pooled extracts from groups of embryos were tested for vertical virus transmission by the nonproducer cell activation test. 2) Only eggs from dams that did not congenitally shed virus to their embryos were used to produce progeny. The offspring were reared in isolation for 2 months (at which time the age-related resistance against tumor formation had developed sufficiently). 3) The birds were subsequently inoculated im with 10(5) mean tissue culture infective doses of LL viruses of subgroups A and B and transferred to a conventional chicken house. The controlled exposure provided immunity against LL virus infection in a highly infect environment. This procedure resulted in birds a) with no boservable LL, and b) producing LL virus-free eggs. To obtain flocks that had no LL and produced virus-free progeny, the procedure had to be repeated for at least two generations due to the intermittent virus excretion that often occurred."}
{"id": "PMID:187795", "title": "Inefficient humoral immune response of lymphoma-prone wild mice to persistent leukemia virus infection.", "content": "Adult wild mice (LC) from a natural colony with a high incidence of spontaneous lymphomas had free infectious virus in their seara (average 10(3.5) infectious units/ml) and parenchymal organs (average 10(5.2) infectious units/g tissue). They did not have detectable levels of free virus-specific antibodies that could be demonstrated by virus neutralization or immunofluorescence at higher than a 1:10 dilution. Only 5 of 28 animals had free antibodies detectable by radioimmunoprecipitation assay, and tissues of 4 mice also had nondetectable levels of virus determined by infectivity assay. Formalized vaccine from the indigenous virus did not induce production of virus-neutralizing antibodies or protect against naturally occurring disease. The animals with persistent leukemia virus infection, however, elicited good humoral immune responses to virus-unrelated antigen.", "contents": "Inefficient humoral immune response of lymphoma-prone wild mice to persistent leukemia virus infection. Adult wild mice (LC) from a natural colony with a high incidence of spontaneous lymphomas had free infectious virus in their seara (average 10(3.5) infectious units/ml) and parenchymal organs (average 10(5.2) infectious units/g tissue). They did not have detectable levels of free virus-specific antibodies that could be demonstrated by virus neutralization or immunofluorescence at higher than a 1:10 dilution. Only 5 of 28 animals had free antibodies detectable by radioimmunoprecipitation assay, and tissues of 4 mice also had nondetectable levels of virus determined by infectivity assay. Formalized vaccine from the indigenous virus did not induce production of virus-neutralizing antibodies or protect against naturally occurring disease. The animals with persistent leukemia virus infection, however, elicited good humoral immune responses to virus-unrelated antigen."}
{"id": "PMID:187796", "title": "Mammary tumorigenesis in chemical carcinogen-treated mice. VI. Tumor-producing capabilities of mammary dysplasias in BALB/cCrgl mice.", "content": "Two types of mammary dysplasias occurring in 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/cCrgl mice were transplanted into the cleared mammary fat pads of syngeneic mice for an assessment of their growth behavior and tumor potentials. Keratinized nodules, numerous in DMBA-treated, pituitary isograft-bearing BALB/cCrgl mice, produced primarily ductal outgrowth in control mice and very few tumors (7%) 56 weeks after transplantation. Such dysplasias transplanted into mice bearing pituitary isografts exhibited lobuloalveolar development and produced a higher incidence of tumors (32%). Hyperplastic alveolar nodules (HAN), though relatively rare in DMBA-treated BALB/cCrgl mice, produced lobuloalveolar outgrowth in control mice and had a 100% tumor incidence. Four HAN outgrowth lines were developed by serial transplantation of samples of the nodule outgrowths. The tumor potentials of these nodule lines in intact controls and ovariectomized mice was determined over several transplant generations. The tumor potentials of two of the three nodule lines were decreased in the absence of ovarian hormones. However, the growth of 23 mammary tumors derived from these nodule lines and of nine derived from in situ primary tumors was unaffected by the absence of the ovary. These results, along with those published previously, suggest that mammary tumors in chemical carcinogen-treated mice arise from several precursor populations. These preneoplastic populations comprise both alveolar and ductal hyperplasias.", "contents": "Mammary tumorigenesis in chemical carcinogen-treated mice. VI. Tumor-producing capabilities of mammary dysplasias in BALB/cCrgl mice. Two types of mammary dysplasias occurring in 7,12-dimethylbenz[a]anthracene (DMBA)-treated BALB/cCrgl mice were transplanted into the cleared mammary fat pads of syngeneic mice for an assessment of their growth behavior and tumor potentials. Keratinized nodules, numerous in DMBA-treated, pituitary isograft-bearing BALB/cCrgl mice, produced primarily ductal outgrowth in control mice and very few tumors (7%) 56 weeks after transplantation. Such dysplasias transplanted into mice bearing pituitary isografts exhibited lobuloalveolar development and produced a higher incidence of tumors (32%). Hyperplastic alveolar nodules (HAN), though relatively rare in DMBA-treated BALB/cCrgl mice, produced lobuloalveolar outgrowth in control mice and had a 100% tumor incidence. Four HAN outgrowth lines were developed by serial transplantation of samples of the nodule outgrowths. The tumor potentials of these nodule lines in intact controls and ovariectomized mice was determined over several transplant generations. The tumor potentials of two of the three nodule lines were decreased in the absence of ovarian hormones. However, the growth of 23 mammary tumors derived from these nodule lines and of nine derived from in situ primary tumors was unaffected by the absence of the ovary. These results, along with those published previously, suggest that mammary tumors in chemical carcinogen-treated mice arise from several precursor populations. These preneoplastic populations comprise both alveolar and ductal hyperplasias."}
{"id": "PMID:187797", "title": "An experimental animal model for the study of human scirrhous carcinoma.", "content": "Scirrhous-like carcinomas were induced by the inoculation of cloned mouse mammary carcinoma cells into the cleared fat pads of BALB/c mice. The inoculated cells induced palpable tumors in 100% of the animals within 60 days. The epithelial cells in vivo grew in rows and clusters and were attached by short developing desmosomes. Microvilli and organelles were scarce; intracisternal type A particles were observed in all the epithelial cells. Carcinoma cells invaded the dermis and muscle. The stroma was formed by morphologically normal fibroblasts and large masses of collagen. No virus particles were observed budding from the epithelial cell surface or in the stromal fibroblasts. The similarities between the scirrhous-like carcinoma in BLAB/c mice and the juman scirrhous carcinoma suggest this animal system as a model for the study of the human disease.", "contents": "An experimental animal model for the study of human scirrhous carcinoma. Scirrhous-like carcinomas were induced by the inoculation of cloned mouse mammary carcinoma cells into the cleared fat pads of BALB/c mice. The inoculated cells induced palpable tumors in 100% of the animals within 60 days. The epithelial cells in vivo grew in rows and clusters and were attached by short developing desmosomes. Microvilli and organelles were scarce; intracisternal type A particles were observed in all the epithelial cells. Carcinoma cells invaded the dermis and muscle. The stroma was formed by morphologically normal fibroblasts and large masses of collagen. No virus particles were observed budding from the epithelial cell surface or in the stromal fibroblasts. The similarities between the scirrhous-like carcinoma in BLAB/c mice and the juman scirrhous carcinoma suggest this animal system as a model for the study of the human disease."}
{"id": "PMID:187798", "title": "Sequential hepatic histologic and histochemical changes produced by diethylnitrosamine in the rhesus monkey.", "content": "Six young adult male rhesus monkeys were given diethylnitrosamine ip for 3-5 years. Liver biospies were done monthly. After 6 months, biopsy specimens showed individual hepatocytes and small foci of hepatocytes that were intensely positive for glycogen. During the second and later years, larger foci of such cells developed. In sections stained with hematoxylin and eosin, the glycogen-containing hepatocytes generally appeared unusually clear. Some hepatocytes, however, had eosinophilic or basophilic cytoplasm. Nuclear enlargement and atypic developed, particularly outside the foci. The hepatocytes within most foci were uniform in their histochemical features: glycogen was elevated, glucose-6-phosphatase was decreased, and ATPase activity was present not only along the bile canalicular surface but also along the enire cell membrane. After 3-5 years, neoplastic nodules and hepatocarcinomas developed in 5 of 6 animals. Two nodules and particularly the heptocarcinomas differed from the foci in one of more histochemical parameters. The findings suggested that the glycogen-containing, histochemically altered cells of the foci in one or more histochemical parameters. The findings suggested that the glycogen-containing, histochemically altered cells of the foci may be the first step in the development of neoplasia; further steps toward malignancy appeared to be frequently associated with additional alterations, such as loss of sinusoidal ATPase and re-formation of glucose-6-phosphatase.", "contents": "Sequential hepatic histologic and histochemical changes produced by diethylnitrosamine in the rhesus monkey. Six young adult male rhesus monkeys were given diethylnitrosamine ip for 3-5 years. Liver biospies were done monthly. After 6 months, biopsy specimens showed individual hepatocytes and small foci of hepatocytes that were intensely positive for glycogen. During the second and later years, larger foci of such cells developed. In sections stained with hematoxylin and eosin, the glycogen-containing hepatocytes generally appeared unusually clear. Some hepatocytes, however, had eosinophilic or basophilic cytoplasm. Nuclear enlargement and atypic developed, particularly outside the foci. The hepatocytes within most foci were uniform in their histochemical features: glycogen was elevated, glucose-6-phosphatase was decreased, and ATPase activity was present not only along the bile canalicular surface but also along the enire cell membrane. After 3-5 years, neoplastic nodules and hepatocarcinomas developed in 5 of 6 animals. Two nodules and particularly the heptocarcinomas differed from the foci in one of more histochemical parameters. The findings suggested that the glycogen-containing, histochemically altered cells of the foci in one or more histochemical parameters. The findings suggested that the glycogen-containing, histochemically altered cells of the foci may be the first step in the development of neoplasia; further steps toward malignancy appeared to be frequently associated with additional alterations, such as loss of sinusoidal ATPase and re-formation of glucose-6-phosphatase."}
{"id": "PMID:187799", "title": "Transport, phosphorylation, and toxicity of a tricyclic nucleoside in cultured Novikoff rat hepatoma cells and other cell lines and relase of its monophosphate by the cells.", "content": "1,4,5,6,8-Pentaazaacenaphthylene-3-amino-1,5-dihydro-5-methyl-(5-14C)-1-beta-D-ribofuranysly (NSC-154020), a tricyclic 7-deazapurine nucleoside (TCN), was rapidly incorporated into the acid-soluble pool by cultured Novikoff rat hepatoma cells, mouse L-cells, HeLa cells, and HEp-2 cells, but little incorporation into nucleic acids occurred. More than 90% of the intracellular radioactivity was associated with the monophosphate (MP) of the substrate concentration followed normal Michaelis-Menten kinetics. Comparison of the kinetic constants for the uptake of adenosine and the TCN and of the inhibition of their uptake by each other suggests that both were transported by the same system (Michaelis constant approximately 6-10 muM) and with about the same efficiency. The TCN was also phosphorylated in a cellfree extract containing adenosine kinase activity at about the same rate as was adenosine, but not further phosphorylation of the analogue MP occurred. No significant deamination or degradation of the adenosine analogue to its base and ribose-1-phosphate was observed. TCN inhibited the replication of all four types of cells propagated in suspension culture; however, Novikoff cells were several times more sensitive than were the other three cell types, despite the finding that the TCN-MP, probably the main toxic principle, accumulated to about the same concentration in cells of all four lines. Complete inhibition of replication of Novikoff cells were several times more sensitive than were the other three cell types, despite the finding that the TCN-MP, probably the main toxic principle, accumulated to about the same concentration in cells of all four lines. Complete inhibition of replication of Novikoff cells and cell death occurred at concentration as low as 15 muM TCN. At these concentrations, TCN, within 2 hours of its addition, completely inhibited the incorporation of [14C]formate int0 nucleotides and nucleic acids of Novikoff cells. An inhibition of the denovo synthesis of purine and pyrimidines, however, was not the only toxic effect of the TCN since high concentrations of uridine, adenine, guanine, and hypoxanthine, either alone or combined, failed to prevent the inhibition of cell replication by TCN. Also, between 1 and 3 hours of treatment, 70-80% of the Novikoff cells fragmented into four to eight vesicles per cell. These fragments were impermeable to trypan blue, still exhibited some metabolic activity such as the phosphorylation of AMP and TCN, but failed to replicate when the drug was removed. No similar fragmentation was observed with the other cell lines. Novikoff and L-cells rapidly released TCN-MP into the culture fluid. After 4 hours of incubation, 70-100% of the total radioactivity in the medium was associated with the MP. Only a little TCN-MP was released from HeLa and HEp-2 cells. A TCN-resistant mutant of Novikoff cells failed to phosphorylate the analogue and was deficient in adenosine kinase.", "contents": "Transport, phosphorylation, and toxicity of a tricyclic nucleoside in cultured Novikoff rat hepatoma cells and other cell lines and relase of its monophosphate by the cells. 1,4,5,6,8-Pentaazaacenaphthylene-3-amino-1,5-dihydro-5-methyl-(5-14C)-1-beta-D-ribofuranysly (NSC-154020), a tricyclic 7-deazapurine nucleoside (TCN), was rapidly incorporated into the acid-soluble pool by cultured Novikoff rat hepatoma cells, mouse L-cells, HeLa cells, and HEp-2 cells, but little incorporation into nucleic acids occurred. More than 90% of the intracellular radioactivity was associated with the monophosphate (MP) of the substrate concentration followed normal Michaelis-Menten kinetics. Comparison of the kinetic constants for the uptake of adenosine and the TCN and of the inhibition of their uptake by each other suggests that both were transported by the same system (Michaelis constant approximately 6-10 muM) and with about the same efficiency. The TCN was also phosphorylated in a cellfree extract containing adenosine kinase activity at about the same rate as was adenosine, but not further phosphorylation of the analogue MP occurred. No significant deamination or degradation of the adenosine analogue to its base and ribose-1-phosphate was observed. TCN inhibited the replication of all four types of cells propagated in suspension culture; however, Novikoff cells were several times more sensitive than were the other three cell types, despite the finding that the TCN-MP, probably the main toxic principle, accumulated to about the same concentration in cells of all four lines. Complete inhibition of replication of Novikoff cells were several times more sensitive than were the other three cell types, despite the finding that the TCN-MP, probably the main toxic principle, accumulated to about the same concentration in cells of all four lines. Complete inhibition of replication of Novikoff cells and cell death occurred at concentration as low as 15 muM TCN. At these concentrations, TCN, within 2 hours of its addition, completely inhibited the incorporation of [14C]formate int0 nucleotides and nucleic acids of Novikoff cells. An inhibition of the denovo synthesis of purine and pyrimidines, however, was not the only toxic effect of the TCN since high concentrations of uridine, adenine, guanine, and hypoxanthine, either alone or combined, failed to prevent the inhibition of cell replication by TCN. Also, between 1 and 3 hours of treatment, 70-80% of the Novikoff cells fragmented into four to eight vesicles per cell. These fragments were impermeable to trypan blue, still exhibited some metabolic activity such as the phosphorylation of AMP and TCN, but failed to replicate when the drug was removed. No similar fragmentation was observed with the other cell lines. Novikoff and L-cells rapidly released TCN-MP into the culture fluid. After 4 hours of incubation, 70-100% of the total radioactivity in the medium was associated with the MP. Only a little TCN-MP was released from HeLa and HEp-2 cells. A TCN-resistant mutant of Novikoff cells failed to phosphorylate the analogue and was deficient in adenosine kinase."}
{"id": "PMID:187800", "title": "Reduction of rat liver carcinogenicity of 4-nitrosomorpholine by alpha-deuterium substitution.", "content": "Groups of 30 males Sprague-Dawley rats were given 4-nitrosomorpholine-3,3,5,5-d in their drinking water at concentrations of 0.35 and 0.07 X 10(-3) M for 30 weeks. Two similar groups of rats were simultaneously given unlabeled 4-nitrosomorpholine (NM) at the same malar concentrations; all animals were observed throughout their lives. Those receiving the alpha-deuterium-labeled compound had significantly fewer liver tumors than did the corresponding animals receiving the unlabeled compound. The difference in potency appeared to be at least fivefold, a magnitude consistent with a primary kinetic isotope effect on the carcinogenic action of NM. Thus breakage of a bond linking a hydrogen (deuterium) atom with carbon adjacent to the nitrosamino function may be involved in a rate-limiting step of carcinogenesis by NM.", "contents": "Reduction of rat liver carcinogenicity of 4-nitrosomorpholine by alpha-deuterium substitution. Groups of 30 males Sprague-Dawley rats were given 4-nitrosomorpholine-3,3,5,5-d in their drinking water at concentrations of 0.35 and 0.07 X 10(-3) M for 30 weeks. Two similar groups of rats were simultaneously given unlabeled 4-nitrosomorpholine (NM) at the same malar concentrations; all animals were observed throughout their lives. Those receiving the alpha-deuterium-labeled compound had significantly fewer liver tumors than did the corresponding animals receiving the unlabeled compound. The difference in potency appeared to be at least fivefold, a magnitude consistent with a primary kinetic isotope effect on the carcinogenic action of NM. Thus breakage of a bond linking a hydrogen (deuterium) atom with carbon adjacent to the nitrosamino function may be involved in a rate-limiting step of carcinogenesis by NM."}
{"id": "PMID:187801", "title": "Carcinogenicity test of two unstaurated derivatives of N-nitrosopiperdine in Sprague-Dawley rats.", "content": "Two unsaturated derivatives of N-nitrosopiperidine (NP), N-nitroso-1,2,3,6-tetrahydropyridine (NTP) and N-nitrosoguvacoline (NGC), were administered to Sprague-Dawley rats as solutions in drinking water at concentrations equimolar (0.88X10(-3) M) with those used to test NP. NTP gave rise to hepatocellular tumors in contrast to the esophageal or olfactory tumors that were induced by NP. NGS did not induce tumors under these test conditions.", "contents": "Carcinogenicity test of two unstaurated derivatives of N-nitrosopiperdine in Sprague-Dawley rats. Two unsaturated derivatives of N-nitrosopiperidine (NP), N-nitroso-1,2,3,6-tetrahydropyridine (NTP) and N-nitrosoguvacoline (NGC), were administered to Sprague-Dawley rats as solutions in drinking water at concentrations equimolar (0.88X10(-3) M) with those used to test NP. NTP gave rise to hepatocellular tumors in contrast to the esophageal or olfactory tumors that were induced by NP. NGS did not induce tumors under these test conditions."}
{"id": "PMID:187802", "title": "Hepatocarcinogenicity of estragole (1-allyl-4-methoxybenzene) and 1'-hydroxyestragole in the mouse and mutagenicity of 1'-acetoxyestragole in bacteria.", "content": "Approximately 20% of a dose of estragole, a naturally occurring flavoring agent, was excreted in the urine of outbred male CD -1 mice as a conjuage (presumably the glucuronide) of 1'-hydroxyestragole, Estragole and its 1'-hydroxy metabolite caused significant increases in the incidences of hepatocellular carcinomas in male CD-1 mice that received the compounds by sc injection at 1-22 days of age. Estragole induced hepatocellular carcinomas by 15 months in 23 and 39% of the mice that received total doses of 4.4 and 5.2 mumoles, respectively, and lived to an age of 12 months or more. Of the 12-month survivors given a total dose of 4.4 mumoles of 1'-hydroxyestragole, 70% developed hepatocellular carcinomas; the incidence in mice that received only the vehicle (trioctanoin) was 12%. Multiple tumors ocurred in 5, 28, 64, and 0%, respectively, of the mice in each of these 4 groups. Of the mice given a total dose of 4.4 mumoles of 1'-hydroxysafrole, 59developed hepatocellular carcinomas; 39% of the mice bore multiple liver tumors. As previsously demonstrated for 1'-acetoxysafrole, 1'-acetoxyestragole and 1'-acetoxy-1-allyl-4-methoxynaphthalene reacted nonenzymatically with guanosine and inosine to form adducts. These electrophilic esters were strongly mutagenic for the Salmonella typhimurium missense mutant TA100. 1'-Acetoxyallybenzene had little or no activity in either of these tests. Attempts to demonstrate liver-mediated mutagenicty for 1'-hydroxysafrole and 1'-hydroxyestragole in the bacterial test system were unsuccessful.", "contents": "Hepatocarcinogenicity of estragole (1-allyl-4-methoxybenzene) and 1'-hydroxyestragole in the mouse and mutagenicity of 1'-acetoxyestragole in bacteria. Approximately 20% of a dose of estragole, a naturally occurring flavoring agent, was excreted in the urine of outbred male CD -1 mice as a conjuage (presumably the glucuronide) of 1'-hydroxyestragole, Estragole and its 1'-hydroxy metabolite caused significant increases in the incidences of hepatocellular carcinomas in male CD-1 mice that received the compounds by sc injection at 1-22 days of age. Estragole induced hepatocellular carcinomas by 15 months in 23 and 39% of the mice that received total doses of 4.4 and 5.2 mumoles, respectively, and lived to an age of 12 months or more. Of the 12-month survivors given a total dose of 4.4 mumoles of 1'-hydroxyestragole, 70% developed hepatocellular carcinomas; the incidence in mice that received only the vehicle (trioctanoin) was 12%. Multiple tumors ocurred in 5, 28, 64, and 0%, respectively, of the mice in each of these 4 groups. Of the mice given a total dose of 4.4 mumoles of 1'-hydroxysafrole, 59developed hepatocellular carcinomas; 39% of the mice bore multiple liver tumors. As previsously demonstrated for 1'-acetoxysafrole, 1'-acetoxyestragole and 1'-acetoxy-1-allyl-4-methoxynaphthalene reacted nonenzymatically with guanosine and inosine to form adducts. These electrophilic esters were strongly mutagenic for the Salmonella typhimurium missense mutant TA100. 1'-Acetoxyallybenzene had little or no activity in either of these tests. Attempts to demonstrate liver-mediated mutagenicty for 1'-hydroxysafrole and 1'-hydroxyestragole in the bacterial test system were unsuccessful."}
{"id": "PMID:187803", "title": "Endogenous oncornaviruses in chemically induced transformation. II. Effect of virus production in vivo.", "content": "C3H/HeJ and AKR/J mice differed in their susceptibility to 3-methylcholantrhene (MCA)-induced sarcomagenesis (86% incidence of sarcomas in C3H by 18 wk; 5% incidence in AKR by 18 wk) and in the production of endogenous murine leukemia virus (MuLV) (AKR produced greater than 10(5) plaque-forming units/ml tail extract in XC test; C3H did not produce detectable virus.) A genetic corss between C3H and AKR mice was examined to determine the relationship of virus production to oncogenesis by MCA. Mice of the (C3H X AKR)F X C3H backcross were typed for the production of infectious MuLV by tail biospy and then inoculated with MCA. Of the backcross mice, 81% produced high titers of ecotropic MuLV; the remaining 19% did not contain detectable infectious MuLV. The virus-producing and non-virus-producing backcross mice were equally sensitive and highly susceptible to MCA-induced sarcomagenesis. Tumors of all virus-positive mice contained infectious MuLV. Some tumors (54%) of virus-negative mice also contained infectious MuLV; this indicated the induction of endogenous MuLV in the tumors of these mice. We concluded that the overt production of MuLV in mice of this backcross did not function in the sensitivity of the mice to sarcoma induction by MCA. Furthermore, the presence of virus in some chemically induced tumors was due to an induction pehnomenon independent of the primary oncogenic event.", "contents": "Endogenous oncornaviruses in chemically induced transformation. II. Effect of virus production in vivo. C3H/HeJ and AKR/J mice differed in their susceptibility to 3-methylcholantrhene (MCA)-induced sarcomagenesis (86% incidence of sarcomas in C3H by 18 wk; 5% incidence in AKR by 18 wk) and in the production of endogenous murine leukemia virus (MuLV) (AKR produced greater than 10(5) plaque-forming units/ml tail extract in XC test; C3H did not produce detectable virus.) A genetic corss between C3H and AKR mice was examined to determine the relationship of virus production to oncogenesis by MCA. Mice of the (C3H X AKR)F X C3H backcross were typed for the production of infectious MuLV by tail biospy and then inoculated with MCA. Of the backcross mice, 81% produced high titers of ecotropic MuLV; the remaining 19% did not contain detectable infectious MuLV. The virus-producing and non-virus-producing backcross mice were equally sensitive and highly susceptible to MCA-induced sarcomagenesis. Tumors of all virus-positive mice contained infectious MuLV. Some tumors (54%) of virus-negative mice also contained infectious MuLV; this indicated the induction of endogenous MuLV in the tumors of these mice. We concluded that the overt production of MuLV in mice of this backcross did not function in the sensitivity of the mice to sarcoma induction by MCA. Furthermore, the presence of virus in some chemically induced tumors was due to an induction pehnomenon independent of the primary oncogenic event."}
{"id": "PMID:187804", "title": "Promotion of tumor growth in vivo by antimacrophage agents.", "content": "Various attempts were made to assess the role of the mononuclear phagocyte system in tumor resistance of rats in vivo. The growth of sc inoculated, weakly immunogenic, carcinogen-induced, syngeneic tumor cells was modestly reduced by ip injection and, more impressively, by local injection of peptone-induced, activated, nonimmune macrophages. A single iv injection of silica particles or carrageenan on the day of sc tumor cell inoculation greatly enhanced tumor growth. When these agents had been given a few days before or after tumor cell inoculation, the tumor-promoting efficiency was distintly diminished or even cancelled. The enhancing effects of silica and carrageenan on tumor growth were nulified by the macrophage-stabilizing agent, poly-2-vinylpyridine N-oxide, To assess the in vivo consequences of silica administration, various cellular, biochemical, and functional macrophage parameters were determined at different intervals. Results indicated the complexity of events elicited after the mononuclear phagoycte system was damaged, which made the interpretation of such results difficult.", "contents": "Promotion of tumor growth in vivo by antimacrophage agents. Various attempts were made to assess the role of the mononuclear phagocyte system in tumor resistance of rats in vivo. The growth of sc inoculated, weakly immunogenic, carcinogen-induced, syngeneic tumor cells was modestly reduced by ip injection and, more impressively, by local injection of peptone-induced, activated, nonimmune macrophages. A single iv injection of silica particles or carrageenan on the day of sc tumor cell inoculation greatly enhanced tumor growth. When these agents had been given a few days before or after tumor cell inoculation, the tumor-promoting efficiency was distintly diminished or even cancelled. The enhancing effects of silica and carrageenan on tumor growth were nulified by the macrophage-stabilizing agent, poly-2-vinylpyridine N-oxide, To assess the in vivo consequences of silica administration, various cellular, biochemical, and functional macrophage parameters were determined at different intervals. Results indicated the complexity of events elicited after the mononuclear phagoycte system was damaged, which made the interpretation of such results difficult."}
{"id": "PMID:187805", "title": "Combination chemotherapy of L1210 leukemia with platinum compounds and cyclophosphamide plus other selected antineoplastic agents.", "content": "Six antitumor platinum compounds were used in combination with cyclophosphamide plut 1 of 7 other antitumor drugs for treatment of L1210 leukemia in B6D2F [C57BL/6 X DMA/2) F] mice. Data obtained from each three-agent regimen were compared with those obtained after administration of each compound alone and each appropriate two-agent combination. No cure (greater than 60-day survival) was obtained with any compound used alone. Combination of cyclophosphamide with a platinum compound (Pt+CY) yielded a collective cure rate of 193/420, and the addition of a third cure rate to 290/420 (P less than 0.001). Certain regimens produced 100% cure rates. The most effective drugs when used in combination with PT+CY were cytosine arabinoside, 5-fluorouracil, hydroxyurea, and Yoshi-864. Adriamycin, methotrexate, and vincristine were less effective at the doses used. Toxicity, as evidenced by maximum weight loss, was slightly greater with the three-agent combinations than with the Pt+CY regimens.", "contents": "Combination chemotherapy of L1210 leukemia with platinum compounds and cyclophosphamide plus other selected antineoplastic agents. Six antitumor platinum compounds were used in combination with cyclophosphamide plut 1 of 7 other antitumor drugs for treatment of L1210 leukemia in B6D2F [C57BL/6 X DMA/2) F] mice. Data obtained from each three-agent regimen were compared with those obtained after administration of each compound alone and each appropriate two-agent combination. No cure (greater than 60-day survival) was obtained with any compound used alone. Combination of cyclophosphamide with a platinum compound (Pt+CY) yielded a collective cure rate of 193/420, and the addition of a third cure rate to 290/420 (P less than 0.001). Certain regimens produced 100% cure rates. The most effective drugs when used in combination with PT+CY were cytosine arabinoside, 5-fluorouracil, hydroxyurea, and Yoshi-864. Adriamycin, methotrexate, and vincristine were less effective at the doses used. Toxicity, as evidenced by maximum weight loss, was slightly greater with the three-agent combinations than with the Pt+CY regimens."}
{"id": "PMID:187822", "title": "Effect of adrenergic agonists on the cyclic AMP level in the liver and heart from normal and hypothyroid rats.", "content": "In order to clarify the mechanism of the different sensitivity of the adrenoceptors between normal and hypothyroid rats, cyclic AMP levels in the liver and heart were measured after the administration of phenylephrine, isoproterenol, epinephrine and methoxamine. Cyclic AMP increased in all cases, but the extent of its increment in the heart was much less than that in the liver. Phentolamine and propranolol showed only a partial inhibition of cyclic AMP elevation by the agonists in the liver from normal and hypothyroid rat. On the other hand, propranolol blocked completely the effect of the agonists on the heart from both groups. It was also observed that cyclic AMP increased in adrenalectomized rats after the injection of the adrenergic agonists. The basal activity of protein kinase in hypothyroid status was slightly lower than that in the normal, but this enzyme was stimulated in the presence of cyclic AMP in vitro. These results suggest that the function of beta-adrenoceptor remained normal even in hypothyroidism and responded well to isoproterenol and epinephrine. It is also indicated that the increased sensitivity of alpha-adrenoceptor to phenylephrine in the hy pothyroid atria previously observed is probably in part independent of the mechanism mediated by cyclic AMP.", "contents": "Effect of adrenergic agonists on the cyclic AMP level in the liver and heart from normal and hypothyroid rats. In order to clarify the mechanism of the different sensitivity of the adrenoceptors between normal and hypothyroid rats, cyclic AMP levels in the liver and heart were measured after the administration of phenylephrine, isoproterenol, epinephrine and methoxamine. Cyclic AMP increased in all cases, but the extent of its increment in the heart was much less than that in the liver. Phentolamine and propranolol showed only a partial inhibition of cyclic AMP elevation by the agonists in the liver from normal and hypothyroid rat. On the other hand, propranolol blocked completely the effect of the agonists on the heart from both groups. It was also observed that cyclic AMP increased in adrenalectomized rats after the injection of the adrenergic agonists. The basal activity of protein kinase in hypothyroid status was slightly lower than that in the normal, but this enzyme was stimulated in the presence of cyclic AMP in vitro. These results suggest that the function of beta-adrenoceptor remained normal even in hypothyroidism and responded well to isoproterenol and epinephrine. It is also indicated that the increased sensitivity of alpha-adrenoceptor to phenylephrine in the hy pothyroid atria previously observed is probably in part independent of the mechanism mediated by cyclic AMP."}
{"id": "PMID:187829", "title": "[Differential diagnostic problems resulting from massive doses of vitamin D and suspected pituitary dwarfism in the father of a child with vitamin-D-resistant rachitis (author's transl)].", "content": "A 1.8-year-old female child with retarded statomotor development and growth was reported. Radiologically and chemically, a rachitis was found which clearly improved following administration of 600,000 U. vitamin D3. Examination of the father who was thought to be suffering from pituitary dwarfism revealed hypophosphatemia and radiologic signs of osteomalacia. The diagnosis of a hypophosphatemic vitamin-D-resistant rachitis in this child could only be established with certainty during the course of the following months.", "contents": "[Differential diagnostic problems resulting from massive doses of vitamin D and suspected pituitary dwarfism in the father of a child with vitamin-D-resistant rachitis (author's transl)]. A 1.8-year-old female child with retarded statomotor development and growth was reported. Radiologically and chemically, a rachitis was found which clearly improved following administration of 600,000 U. vitamin D3. Examination of the father who was thought to be suffering from pituitary dwarfism revealed hypophosphatemia and radiologic signs of osteomalacia. The diagnosis of a hypophosphatemic vitamin-D-resistant rachitis in this child could only be established with certainty during the course of the following months."}
{"id": "PMID:187830", "title": "[Clinical and diagnostical aspects of acute cytomegalovirus infections in previously healthy adults (author's transl)].", "content": "The clinical symptoms of floride Cytomegalovirus infections of 18 previously healthy adults are reported. Fever was generally observed. In most cases myocarditis or hepatitis could be identified. Two of our patients died of on severe myocarditis. In 3 patients Guillain-Barr\u00e9-syndrome was observed. Only in few of our cases the clinical picture was characterized by mononucleosis with systemic swelling of lymphonodes and thrombocytopenia or by pneumonia. Other symptoms were found quite seldom. The diagnosis of cytomegalovirus infection could be ascertained by: 1. detection of cytomegalovirus IgM antibody titers of greater 1:64, 2. a four fold increase in the titer of complement fixing antibodies, 3. Virus isolation from urine.", "contents": "[Clinical and diagnostical aspects of acute cytomegalovirus infections in previously healthy adults (author's transl)]. The clinical symptoms of floride Cytomegalovirus infections of 18 previously healthy adults are reported. Fever was generally observed. In most cases myocarditis or hepatitis could be identified. Two of our patients died of on severe myocarditis. In 3 patients Guillain-Barr\u00e9-syndrome was observed. Only in few of our cases the clinical picture was characterized by mononucleosis with systemic swelling of lymphonodes and thrombocytopenia or by pneumonia. Other symptoms were found quite seldom. The diagnosis of cytomegalovirus infection could be ascertained by: 1. detection of cytomegalovirus IgM antibody titers of greater 1:64, 2. a four fold increase in the titer of complement fixing antibodies, 3. Virus isolation from urine."}
{"id": "PMID:187876", "title": "Properties of calf endothelial cells in culture.", "content": "Calf aorta endothelial cells, obtained by collagenase treatment of vessels from freshly killed animals, were cultured in medium 199 supplemented with fetal bovine serum, amino acids, and vitamins. The material released from the vessel wall after collagenase treatment consists of clumps of cells which quickly attach to the dish and spread to form confluent islands of cells. These islands of cells coalesce to form a confluent monolayer in 6 to 8 days. Cultures labeled with [3H]thymidine show an increase in labeling commencing 3 days after initial culture. Cells within monolayers do not overgrow one another and retain their epithelioid appearance after subculture. Identification of endothelial cells was based on culture morphology and by the presence of factor VIII antigen as localized by indirect immunofluorescence microscopy. These data indicate that large numbers of endothelial cells (5 to 7 x 10(6) cells per aorta) can be obtained and maintained in culture.", "contents": "Properties of calf endothelial cells in culture. Calf aorta endothelial cells, obtained by collagenase treatment of vessels from freshly killed animals, were cultured in medium 199 supplemented with fetal bovine serum, amino acids, and vitamins. The material released from the vessel wall after collagenase treatment consists of clumps of cells which quickly attach to the dish and spread to form confluent islands of cells. These islands of cells coalesce to form a confluent monolayer in 6 to 8 days. Cultures labeled with [3H]thymidine show an increase in labeling commencing 3 days after initial culture. Cells within monolayers do not overgrow one another and retain their epithelioid appearance after subculture. Identification of endothelial cells was based on culture morphology and by the presence of factor VIII antigen as localized by indirect immunofluorescence microscopy. These data indicate that large numbers of endothelial cells (5 to 7 x 10(6) cells per aorta) can be obtained and maintained in culture."}
{"id": "PMID:187878", "title": "Cyclic nucleotides, thioldisulfide status of proteins, and cellular control processes.", "content": "It is shown that cyclic nucleotides can have a variety of effects on cell division, cell shape, cell adhesion, and cell movement, depending on the cells selected and the conditions under which they are used. For example, while CHO cells elongate under the influence of exogenous dibutyryl CAMP, Y-1 adrenal tumor cells round up and polyoma-transformed 3T3 cells show no change in shape. The totality of experience with cyclic nucleotides suggests that where they have been used by cells as control elements involving the four processes listed above, they are superimposed on basic cellular processes that progress in their absence--that is, they must be acting indirectly. In attempting to understand the inhibitory action of methyl xanthines on egg development, we were forced to abandon the idea that they acted through cyclic nucleotides. We found that methyl xanthines inhibited the activation of glutathione reductase and that glutathione oxidizing agents act as mitotic inhibitors. Further, we found that tubulin polymerizability, NAD-kinase activity, and a mitotic apparatus associated Ca+2-ATP-ase were all inhibited by oxidation of some of their sulfhydryls and were activated by reduction of the resulting disulfides. These results are discussed in terms of reported cycles and activations of glutathione reductase (GR) in cells and reports that mixed disulfides of glutathione and proteins can act as substrates for GR. Using the fact that a CAMP-dependent protein kinase has been reported to be activated by glutathione, we have suggested potential sites where sulfhydryl control processes and cyclic nucleotide control processes and cyclic nucleotide control processes may interact in certain restricted cases.", "contents": "Cyclic nucleotides, thioldisulfide status of proteins, and cellular control processes. It is shown that cyclic nucleotides can have a variety of effects on cell division, cell shape, cell adhesion, and cell movement, depending on the cells selected and the conditions under which they are used. For example, while CHO cells elongate under the influence of exogenous dibutyryl CAMP, Y-1 adrenal tumor cells round up and polyoma-transformed 3T3 cells show no change in shape. The totality of experience with cyclic nucleotides suggests that where they have been used by cells as control elements involving the four processes listed above, they are superimposed on basic cellular processes that progress in their absence--that is, they must be acting indirectly. In attempting to understand the inhibitory action of methyl xanthines on egg development, we were forced to abandon the idea that they acted through cyclic nucleotides. We found that methyl xanthines inhibited the activation of glutathione reductase and that glutathione oxidizing agents act as mitotic inhibitors. Further, we found that tubulin polymerizability, NAD-kinase activity, and a mitotic apparatus associated Ca+2-ATP-ase were all inhibited by oxidation of some of their sulfhydryls and were activated by reduction of the resulting disulfides. These results are discussed in terms of reported cycles and activations of glutathione reductase (GR) in cells and reports that mixed disulfides of glutathione and proteins can act as substrates for GR. Using the fact that a CAMP-dependent protein kinase has been reported to be activated by glutathione, we have suggested potential sites where sulfhydryl control processes and cyclic nucleotide control processes and cyclic nucleotide control processes may interact in certain restricted cases."}
{"id": "PMID:187879", "title": "Distribution pattern of radioactive labelled lipiodol-UF following intralymphatic application for therapy.", "content": "Endolymphatic radiotherapy with 4 mCi32P tri-n-octylphosphate and 1 mCi 131 I triolein LIPIODOL UF has been performed in 75 patients suffering from malignant melanoma of the lower extremity. On the average, 13.3% of the radioactive substance remains in the syringes and connecting tubes. In most patients the radioactive material available for therapeutic irradiation is further reduced due to contamination of operation sheets and swabs (mean: 15.3%). There is, however, still sufficient radioactivity remaining for effective internal irradiation of the lymph nodes. The average radiation dose absorbed by the lymphatic tissue is 90.998 rad. The method is limited by the hazard of radiation damage to the lungs. Almost 80% of these patients had detectable concentrations of radioactivity in the lung fields. The average radiation dose was found to be 299 rad. So far radiation induced fibrosis has bot been observed in this series.", "contents": "Distribution pattern of radioactive labelled lipiodol-UF following intralymphatic application for therapy. Endolymphatic radiotherapy with 4 mCi32P tri-n-octylphosphate and 1 mCi 131 I triolein LIPIODOL UF has been performed in 75 patients suffering from malignant melanoma of the lower extremity. On the average, 13.3% of the radioactive substance remains in the syringes and connecting tubes. In most patients the radioactive material available for therapeutic irradiation is further reduced due to contamination of operation sheets and swabs (mean: 15.3%). There is, however, still sufficient radioactivity remaining for effective internal irradiation of the lymph nodes. The average radiation dose absorbed by the lymphatic tissue is 90.998 rad. The method is limited by the hazard of radiation damage to the lungs. Almost 80% of these patients had detectable concentrations of radioactivity in the lung fields. The average radiation dose was found to be 299 rad. So far radiation induced fibrosis has bot been observed in this series."}
{"id": "PMID:187881", "title": "Inhibition of neuromuscular transmission by prostaglandin E1 in the circular muscle of the guinea-pig vas deferens.", "content": "Pressure increases elicited by contractions of the circular muscle of the isolated guinea-pig vas deferens in response to nerve stimulation were recorded. In contrast to longitudinal muscle which contracted in response to 1--50 pulses, circular muscle responded only to longer trains of pulses (10--500) at a frequency of 10 Hz. Atropine (1.4 muM) caused a slight depression of responses to 100 shocks. Phentolamine at a concentration of 2.6 muM failed to inhibit the response to stimulation, but a higher concentration (53 muM) caused a definite blockade. Guanethidine (25 muM) strongly reduced the responses. With a stimulus train of 100 pulses no inhibition by prostaglandin E1 (PGE1) (0.028 muM) could be demonstrated; however, at a lower number of shocks (20--50) a clearcut depression was observed. The lower the number of pulses the more marked was the depression. The observation that PGE1 failed to block the contractions evoked by noradrenaline (59 muM) suggests a presynaptic inhibitory action of the prostaglandin. It is suggested that noradrenaline is the transmitter in both muscle coats of the guinea-pig vas deferens and that the neuroeffector junctions are sensitive to the effect of PGE1.", "contents": "Inhibition of neuromuscular transmission by prostaglandin E1 in the circular muscle of the guinea-pig vas deferens. Pressure increases elicited by contractions of the circular muscle of the isolated guinea-pig vas deferens in response to nerve stimulation were recorded. In contrast to longitudinal muscle which contracted in response to 1--50 pulses, circular muscle responded only to longer trains of pulses (10--500) at a frequency of 10 Hz. Atropine (1.4 muM) caused a slight depression of responses to 100 shocks. Phentolamine at a concentration of 2.6 muM failed to inhibit the response to stimulation, but a higher concentration (53 muM) caused a definite blockade. Guanethidine (25 muM) strongly reduced the responses. With a stimulus train of 100 pulses no inhibition by prostaglandin E1 (PGE1) (0.028 muM) could be demonstrated; however, at a lower number of shocks (20--50) a clearcut depression was observed. The lower the number of pulses the more marked was the depression. The observation that PGE1 failed to block the contractions evoked by noradrenaline (59 muM) suggests a presynaptic inhibitory action of the prostaglandin. It is suggested that noradrenaline is the transmitter in both muscle coats of the guinea-pig vas deferens and that the neuroeffector junctions are sensitive to the effect of PGE1."}
{"id": "PMID:187882", "title": "The jugular bulb: its anatomic and clinical considerations in contemporary otology.", "content": "Advances in neurotologic diagnosis and surgery has pointed to the need for a complete reassessment of the relationship and significance of the jugular bulb and sigmoid sinus is discussed and selected temporal bone sections presented to illustrate the varying locations of the jugualr bulb. Considerations in differential diagnosis are presented and examples of surgical procedures are discussed wherein the jugular bulb was encountered and the methods of management are detailed in these instances.", "contents": "The jugular bulb: its anatomic and clinical considerations in contemporary otology. Advances in neurotologic diagnosis and surgery has pointed to the need for a complete reassessment of the relationship and significance of the jugular bulb and sigmoid sinus is discussed and selected temporal bone sections presented to illustrate the varying locations of the jugualr bulb. Considerations in differential diagnosis are presented and examples of surgical procedures are discussed wherein the jugular bulb was encountered and the methods of management are detailed in these instances."}
{"id": "PMID:187883", "title": "Lesions of the vagus nerve: diagnosis, treatment and rehabilitation.", "content": "Lesions of the vagus nervous system have devastating effects on the vital functions of coughing, swallowing and phonation. A clear understanding of the vagal correlative anatomy and physiology leads to a practical organization of upper respiratory and digestive tract lesions. A reasoned and thoughtful treatment plan evolves that leads the patient to comprehensive treatment and rehabilitation.", "contents": "Lesions of the vagus nerve: diagnosis, treatment and rehabilitation. Lesions of the vagus nervous system have devastating effects on the vital functions of coughing, swallowing and phonation. A clear understanding of the vagal correlative anatomy and physiology leads to a practical organization of upper respiratory and digestive tract lesions. A reasoned and thoughtful treatment plan evolves that leads the patient to comprehensive treatment and rehabilitation."}
{"id": "PMID:187902", "title": "[Electron transport chain of the Candida mycoderma mutant lacking cytochromes b and a+a3].", "content": "Two electrontransport chains--\"oxygen\" and \"peroxidase\"--were found to operate in the mutant of Candida mycoderma lacking cytochromes b and a+a3; the terminal acceptors of electrons are oxygen and hydrogen peroxide, respectively. The \"oxygen\" chain lacks cytochromes but contains pyridine nucleotides and flavoproteins; it is inhibited by rotenone and benzhydroxamic acid. The \"peroxidase\" chain consists of pyridine nucleotides, cytochrome c, and cytochrome c peroxidase; it is inhibited by cyanide.", "contents": "[Electron transport chain of the Candida mycoderma mutant lacking cytochromes b and a+a3]. Two electrontransport chains--\"oxygen\" and \"peroxidase\"--were found to operate in the mutant of Candida mycoderma lacking cytochromes b and a+a3; the terminal acceptors of electrons are oxygen and hydrogen peroxide, respectively. The \"oxygen\" chain lacks cytochromes but contains pyridine nucleotides and flavoproteins; it is inhibited by rotenone and benzhydroxamic acid. The \"peroxidase\" chain consists of pyridine nucleotides, cytochrome c, and cytochrome c peroxidase; it is inhibited by cyanide."}
{"id": "PMID:187903", "title": "[Characteristics of the respiratory chain and the oxidative phosphorylation system of mitochondria in the flavinogenic Eremothecium ashbyii strain].", "content": "Tightly coupled mitochondria were isolated from cells of the flavinogenic strain of Eremothecium ashbyii collected during the logarithmic and stationary growth phases. The composition of the respiratory chain and characteristics of the energy coupling system are described. The mitochondria show a wide spectrum of metabolic activity and oxidize Krebs cycle compenents and exogenous NADH. The terminal segment of the respiratory chain is represented by a typical cytochrome system. The mitochondria of the ascomycete collected during the logarithmic growth phase are characterized by a relatively high content of cytochromes b and c, a high rate of oxidation of NAD-dependent substrates, the presence of lower homologues of ubiquinone, UQ6 and UQ7, and extremely high sensitivity of respiration to the action of antimycin A, low content of a component sensitive to rotenone, contrasting with the operation of all three sites of phosphorylation. Transition to the stationary growth phase is accompanied with a decrease in the rate of oxidation of all substrates studied and a declined effectiveness of oxidative phosphorylation. The data obtained are discussed in relation to the ability of the cells for \"overproduction\" of flavins.", "contents": "[Characteristics of the respiratory chain and the oxidative phosphorylation system of mitochondria in the flavinogenic Eremothecium ashbyii strain]. Tightly coupled mitochondria were isolated from cells of the flavinogenic strain of Eremothecium ashbyii collected during the logarithmic and stationary growth phases. The composition of the respiratory chain and characteristics of the energy coupling system are described. The mitochondria show a wide spectrum of metabolic activity and oxidize Krebs cycle compenents and exogenous NADH. The terminal segment of the respiratory chain is represented by a typical cytochrome system. The mitochondria of the ascomycete collected during the logarithmic growth phase are characterized by a relatively high content of cytochromes b and c, a high rate of oxidation of NAD-dependent substrates, the presence of lower homologues of ubiquinone, UQ6 and UQ7, and extremely high sensitivity of respiration to the action of antimycin A, low content of a component sensitive to rotenone, contrasting with the operation of all three sites of phosphorylation. Transition to the stationary growth phase is accompanied with a decrease in the rate of oxidation of all substrates studied and a declined effectiveness of oxidative phosphorylation. The data obtained are discussed in relation to the ability of the cells for \"overproduction\" of flavins."}
{"id": "PMID:187904", "title": "[Phospholipase C of fungi and staphylococci].", "content": "The activity of phospholipase was studied in the cultural broth and cell extract of 112 strains of fungi and yeasts. The endoenzyme was detected in 19 strains of mycelial fungi, the exoenzyme was found in Mucor hiemalis 50 and Aspergillus niger 117. Phospholipase C of M. hiemalis was purified and compared to phospholipase of staphylococci. The values of Km are 8.9 and 1.07 mM, respectively, for the fungal and staphylococcal enzymes.", "contents": "[Phospholipase C of fungi and staphylococci]. The activity of phospholipase was studied in the cultural broth and cell extract of 112 strains of fungi and yeasts. The endoenzyme was detected in 19 strains of mycelial fungi, the exoenzyme was found in Mucor hiemalis 50 and Aspergillus niger 117. Phospholipase C of M. hiemalis was purified and compared to phospholipase of staphylococci. The values of Km are 8.9 and 1.07 mM, respectively, for the fungal and staphylococcal enzymes."}
{"id": "PMID:187905", "title": "[Effect of calcium hypochlorite on Bacillus anthracoides spores].", "content": "The sublethal dose of calcium hypochlorite (CH) of 0.2--0.3 mg/ml active chlorine did not cause, after 5 min, morphological changes in the spores of Bacillus anthracoides which could be detected by phase contrast microscopy, or a decrease in the content of dipicolinic acid (DPA) in the spores. Further cultivation of the spores treated with the sublethal dose of CH om MPA resulted in a delay of changes which were typical of normal germination process (swelling, loss of light refraction, decrease in DPA content). The action of the lethal dose of CH (0.2--0.3 mg/ml active chlorine during 1.5 hr or 5.6 mg/ml active chlorine during 1 hr) causes a decrease in light refraction, changes in the dimensions of spores, and a decrease in the content of DPA in the spores by a factor of 4--5. A sharp decrease in the content of DPA in the spores may characterize not only their germination but also their death caused by lethal doses of the chlorine containing disinfectant.", "contents": "[Effect of calcium hypochlorite on Bacillus anthracoides spores]. The sublethal dose of calcium hypochlorite (CH) of 0.2--0.3 mg/ml active chlorine did not cause, after 5 min, morphological changes in the spores of Bacillus anthracoides which could be detected by phase contrast microscopy, or a decrease in the content of dipicolinic acid (DPA) in the spores. Further cultivation of the spores treated with the sublethal dose of CH om MPA resulted in a delay of changes which were typical of normal germination process (swelling, loss of light refraction, decrease in DPA content). The action of the lethal dose of CH (0.2--0.3 mg/ml active chlorine during 1.5 hr or 5.6 mg/ml active chlorine during 1 hr) causes a decrease in light refraction, changes in the dimensions of spores, and a decrease in the content of DPA in the spores by a factor of 4--5. A sharp decrease in the content of DPA in the spores may characterize not only their germination but also their death caused by lethal doses of the chlorine containing disinfectant."}
{"id": "PMID:187912", "title": "[Paul-Bunnell negative glandular fever (author's transl)].", "content": "Cytomegalovirus infections may occur either as congenital and neonatal diseases respectively or postnatally in adults in connection with conditions of antibody or immunologic deficiencies. Reports of postnatally acquired cytomegalovirus infections in apparently healthy adults are scarce. A case of an acquired cytomegalo-virus infection in a 23-year old male patient who never was ill before is reported. Clinical and laboratory features showed a typical course of a Paul-Bunnell negative glandular fever. Diagnosis could be established by detection of cytomegalovirus IgM serum levels by means of immunofluorescence technique.", "contents": "[Paul-Bunnell negative glandular fever (author's transl)]. Cytomegalovirus infections may occur either as congenital and neonatal diseases respectively or postnatally in adults in connection with conditions of antibody or immunologic deficiencies. Reports of postnatally acquired cytomegalovirus infections in apparently healthy adults are scarce. A case of an acquired cytomegalo-virus infection in a 23-year old male patient who never was ill before is reported. Clinical and laboratory features showed a typical course of a Paul-Bunnell negative glandular fever. Diagnosis could be established by detection of cytomegalovirus IgM serum levels by means of immunofluorescence technique."}
{"id": "PMID:187910", "title": "Genetic, endocrine, and viral aspects of AKR leukemogenesis.", "content": "In the AKR strain of mice a high incidence of spontaneous lymphoid leukemia develops before 12 months of age. Genetic, viral, and endocrine factors interact during development to produce the syndrome. Many of the deficiencies of AKR mice are associated with gene action in chromosome 17, at or near the major histocompatibility locus. It is suggested that low steroid levels and high thyroxin levels during an early period of development are an essential part of the syndrome. Specifically, induction of a polymerase enzyme and regulation of the extent of its action by hormones are postulated to favor appearance of C-type particles and accumulation of a population of undifferentiated lymphoid stem cells. Immunodeficiency and leukemic transformation result.", "contents": "Genetic, endocrine, and viral aspects of AKR leukemogenesis. In the AKR strain of mice a high incidence of spontaneous lymphoid leukemia develops before 12 months of age. Genetic, viral, and endocrine factors interact during development to produce the syndrome. Many of the deficiencies of AKR mice are associated with gene action in chromosome 17, at or near the major histocompatibility locus. It is suggested that low steroid levels and high thyroxin levels during an early period of development are an essential part of the syndrome. Specifically, induction of a polymerase enzyme and regulation of the extent of its action by hormones are postulated to favor appearance of C-type particles and accumulation of a population of undifferentiated lymphoid stem cells. Immunodeficiency and leukemic transformation result."}
{"id": "PMID:187911", "title": "Provocation poliomyelitis and entry of poliovirus to the CNS.", "content": "It is proposed that entry to the CNS by poliovirus occurs from multiple sites which are seeded during viremia. At each site, an inflammatory reaction allows entry to peripheral nerves. Differences in incubation times are related to the length of nerve to be followed. Virus reaches the CNS sequentially but does not in natural poliomyelitis spread within the CNS. Provoking agents are identified as immunogenic and their action explained. Details of paralysis among Cutter vaccinees are explained by this model, as well as the effects of multiple inoculation in monkeys. Clinical symptoms in the preparalytic stage of poliomyelitis are consistent with this model.", "contents": "Provocation poliomyelitis and entry of poliovirus to the CNS. It is proposed that entry to the CNS by poliovirus occurs from multiple sites which are seeded during viremia. At each site, an inflammatory reaction allows entry to peripheral nerves. Differences in incubation times are related to the length of nerve to be followed. Virus reaches the CNS sequentially but does not in natural poliomyelitis spread within the CNS. Provoking agents are identified as immunogenic and their action explained. Details of paralysis among Cutter vaccinees are explained by this model, as well as the effects of multiple inoculation in monkeys. Clinical symptoms in the preparalytic stage of poliomyelitis are consistent with this model."}
{"id": "PMID:187915", "title": "Inhibition of EB virus transformation of non-adherent human lymphocytes by co-cultivation with adult fibroblasts.", "content": "Transformation of a special population of non-adherent human lymphocytes by EB virus (EBV) is reversibly inhibited by co-cultivation on adult human fibroblasts. Neither fluid from adult fibroblast cultures nor extracts of fibroblasts inhibited such transformation, and the growth of already transformed lymphocytes was not inhibited on adult fibroblasts. The EBV-associated nuclear antigen (EBNA) was detectable in inhibited cultures, with a maximum level of about 15% at 14 days after which it decreased gradually. Reversal of inhibition at 28 days, by either addition of phytohaemagglutinin or by removal of the lymphocytes from the adult fibroblasts, resulted in a prompt increase in the percentage of EBNA-positive cells and typical lymphoblastoid outgrowth. Transformation of EBV-infected non-adherent lymphocytes could be inhibited by the addition of adult fibroblasts up to 2-4 days after infection. The results indicate that, in the EBV-infection of non-adherent lymphocytes on adult fibroblasts, a block resulting in inhibition of transformation occurs between the production of EBNA and the onset of autonomous proliferation of the infected lymphocytes.", "contents": "Inhibition of EB virus transformation of non-adherent human lymphocytes by co-cultivation with adult fibroblasts. Transformation of a special population of non-adherent human lymphocytes by EB virus (EBV) is reversibly inhibited by co-cultivation on adult human fibroblasts. Neither fluid from adult fibroblast cultures nor extracts of fibroblasts inhibited such transformation, and the growth of already transformed lymphocytes was not inhibited on adult fibroblasts. The EBV-associated nuclear antigen (EBNA) was detectable in inhibited cultures, with a maximum level of about 15% at 14 days after which it decreased gradually. Reversal of inhibition at 28 days, by either addition of phytohaemagglutinin or by removal of the lymphocytes from the adult fibroblasts, resulted in a prompt increase in the percentage of EBNA-positive cells and typical lymphoblastoid outgrowth. Transformation of EBV-infected non-adherent lymphocytes could be inhibited by the addition of adult fibroblasts up to 2-4 days after infection. The results indicate that, in the EBV-infection of non-adherent lymphocytes on adult fibroblasts, a block resulting in inhibition of transformation occurs between the production of EBNA and the onset of autonomous proliferation of the infected lymphocytes."}
{"id": "PMID:187916", "title": "XC cell fusion by murine leukemia viruses: fusion from without.", "content": "Concentrated murine leukemia virus (MuLV) or MuLV producing cells induce XC cell fusion within an hour leading to syncytia formation. While MuLV inactivated by UV irradiation, beta-propiolactone or hydroxylamine treatment still caused cell fusion, Bromelin- or trypsin treated MuLV was no longer able to fuse XC cells. Though sonicated MuLV induced no XC cell fusion, it interfered with cell fusion as caused by untreated MuLV. XC cells infected by diluted MuLV of a titer lower than 1 X 10(5) PFU/ml formed no syncytia although they produced MuLV. The cell fusion mechanism is discussed.", "contents": "XC cell fusion by murine leukemia viruses: fusion from without. Concentrated murine leukemia virus (MuLV) or MuLV producing cells induce XC cell fusion within an hour leading to syncytia formation. While MuLV inactivated by UV irradiation, beta-propiolactone or hydroxylamine treatment still caused cell fusion, Bromelin- or trypsin treated MuLV was no longer able to fuse XC cells. Though sonicated MuLV induced no XC cell fusion, it interfered with cell fusion as caused by untreated MuLV. XC cells infected by diluted MuLV of a titer lower than 1 X 10(5) PFU/ml formed no syncytia although they produced MuLV. The cell fusion mechanism is discussed."}
{"id": "PMID:187917", "title": "Neutralizing serum IgM antibodies in infections with Herpes simplex virus hominis.", "content": "Forty-two patients with herpes simplex virus infections were tested for neutralizing serum IgM antibodies. A technique in which serum antibody fluorescein staining was combined with sucrose gradient centrifugation facilitated the isolation of the serum IgM fraction for the use in neutralization tests. In nearly all cases with primary infection, especially those presenting heavy clinical signs (encephalitis/meningitis) the IgM tests were positive. In one case we could detect the IgM antibodies for 11 weeks after the onset of the illness, in another case in cerebrospinal fluid samples for 6 weeks. In localized herpes infections, which were mostly due to reactivations, serum IgM antibodies could only rarely be demonstrated. Among the serologic tests used in this study (NT, CFT, IFT, ACIFT), only the CFT beside the NT (with certain reservations) can be applied for subtyping HSV serum antibodies.", "contents": "Neutralizing serum IgM antibodies in infections with Herpes simplex virus hominis. Forty-two patients with herpes simplex virus infections were tested for neutralizing serum IgM antibodies. A technique in which serum antibody fluorescein staining was combined with sucrose gradient centrifugation facilitated the isolation of the serum IgM fraction for the use in neutralization tests. In nearly all cases with primary infection, especially those presenting heavy clinical signs (encephalitis/meningitis) the IgM tests were positive. In one case we could detect the IgM antibodies for 11 weeks after the onset of the illness, in another case in cerebrospinal fluid samples for 6 weeks. In localized herpes infections, which were mostly due to reactivations, serum IgM antibodies could only rarely be demonstrated. Among the serologic tests used in this study (NT, CFT, IFT, ACIFT), only the CFT beside the NT (with certain reservations) can be applied for subtyping HSV serum antibodies."}
{"id": "PMID:187918", "title": "Recurrent genital Herpes simplex virus (HSV) infection of guinea pigs.", "content": "Intravaginal infection of guinea pigs with HSV type 2 induced lesions resembling genital herpes in humans. Chronic latent infection with spontaneously recurring genital lesions developed in animals surviving the primary disease. Clinical observations and virological studies during the acute and chronic infection are reported.", "contents": "Recurrent genital Herpes simplex virus (HSV) infection of guinea pigs. Intravaginal infection of guinea pigs with HSV type 2 induced lesions resembling genital herpes in humans. Chronic latent infection with spontaneously recurring genital lesions developed in animals surviving the primary disease. Clinical observations and virological studies during the acute and chronic infection are reported."}
{"id": "PMID:187919", "title": "Serum modulation of in vitro cellular immune reactivity to Epstein-Barr virus-associated antigen.", "content": "The reactivity of peripheral blood leukocytes to Epstein-Barr virus-associated antigen was assessed employing two in vitro tests, leukocyte adherence inhibition (LAI) and leukocyte migration inhibition (LMI). In both tests, autologous serum from some normal subjects was shown to confer strong reactivity on weak or non-responder cells. Reactivity to purified protein derivative of tuberculin (PPD) assessed in parallel was shown to be unaffected by autologous serum. Employing the LAI system, variations in the effects of autologous serum samples collected on consecutive days was shown to be dependent on the reactivity of the leukocytes themselves, rather than changes in the activity or concentration of factors present in the serum.", "contents": "Serum modulation of in vitro cellular immune reactivity to Epstein-Barr virus-associated antigen. The reactivity of peripheral blood leukocytes to Epstein-Barr virus-associated antigen was assessed employing two in vitro tests, leukocyte adherence inhibition (LAI) and leukocyte migration inhibition (LMI). In both tests, autologous serum from some normal subjects was shown to confer strong reactivity on weak or non-responder cells. Reactivity to purified protein derivative of tuberculin (PPD) assessed in parallel was shown to be unaffected by autologous serum. Employing the LAI system, variations in the effects of autologous serum samples collected on consecutive days was shown to be dependent on the reactivity of the leukocytes themselves, rather than changes in the activity or concentration of factors present in the serum."}
{"id": "PMID:187923", "title": "The location of the feedback-specific region with the pyrimidine-3 locus of Neurospora crassa.", "content": "The purimidine-3 locus of Neurospora crassa specifies two enzyme activities, pyrimidine-specific carbamyl phosphate synthetase (CPSpyr) and aspartate transcarbamylase (ATC). ATC is translationally distal. CPSpyr, but not ATC, is subject to feedback inhibition by uridine triphosphate (UTP). To investigate the location of the feedback-specific region within the locus, inhibition of a number of pyr-3 alleles by UTP was investigated. All CPS+ ATC- polar alleles, revertants of CPS- ATC- polar alleles, and 5-fluorouracil-resistant mutants had normal UTP response. The location of the feedback-specific region is in or close to the CPS-specific region.", "contents": "The location of the feedback-specific region with the pyrimidine-3 locus of Neurospora crassa. The purimidine-3 locus of Neurospora crassa specifies two enzyme activities, pyrimidine-specific carbamyl phosphate synthetase (CPSpyr) and aspartate transcarbamylase (ATC). ATC is translationally distal. CPSpyr, but not ATC, is subject to feedback inhibition by uridine triphosphate (UTP). To investigate the location of the feedback-specific region within the locus, inhibition of a number of pyr-3 alleles by UTP was investigated. All CPS+ ATC- polar alleles, revertants of CPS- ATC- polar alleles, and 5-fluorouracil-resistant mutants had normal UTP response. The location of the feedback-specific region is in or close to the CPS-specific region."}
{"id": "PMID:187929", "title": "An ESR study of the postsynatpic membrane acetylcholinesterase of Torpedo marmorata electric organ.", "content": "The effect of the cholinergic activator, phenyltrimethylammonium, on the ESR spectra of spin-labeled membrane bound acetylcholinesterase was studied; a reduction of maximal hyperfine splitting of the anisotropic ESR spectrum by 2 G was observed. The influence of phenyltrimethylammonium was prevented by the two cholinergic blocking agents d-tubocurarine and alpha-cobratoxine. The present results indicate that the conformation change of the esteratic site of membrane acetylcholinesterase is triggered by the binding of phenyltrimethylammonium to the cholinoreceptor site.", "contents": "An ESR study of the postsynatpic membrane acetylcholinesterase of Torpedo marmorata electric organ. The effect of the cholinergic activator, phenyltrimethylammonium, on the ESR spectra of spin-labeled membrane bound acetylcholinesterase was studied; a reduction of maximal hyperfine splitting of the anisotropic ESR spectrum by 2 G was observed. The influence of phenyltrimethylammonium was prevented by the two cholinergic blocking agents d-tubocurarine and alpha-cobratoxine. The present results indicate that the conformation change of the esteratic site of membrane acetylcholinesterase is triggered by the binding of phenyltrimethylammonium to the cholinoreceptor site."}
{"id": "PMID:187930", "title": "Hormonal control of fat cells adenylate cyclase.", "content": "Fat cells were preincubated for 2 h in the presence and absence of growth hormone (GH) and Dexamethasone (Dex) before the addition of increasing concentrations of either epinephrine, theophylline or glucagon and final incubation of the cells for an additional 5 minutes. GH and Dex increased by 85%, 28% and 72%, respectively, the cAMP levels reached in the sole presence of 10(-5)M epinephrine, 10(-2)M theophylline or 5 X 10(-5)M glucagon. An adenylate cyclase particulate preparation shows that epinephrine decreases Km from 2mM to 0.6 MM and increases Vmax and the strength of interaction value (n) from 0.91 to 1.75.", "contents": "Hormonal control of fat cells adenylate cyclase. Fat cells were preincubated for 2 h in the presence and absence of growth hormone (GH) and Dexamethasone (Dex) before the addition of increasing concentrations of either epinephrine, theophylline or glucagon and final incubation of the cells for an additional 5 minutes. GH and Dex increased by 85%, 28% and 72%, respectively, the cAMP levels reached in the sole presence of 10(-5)M epinephrine, 10(-2)M theophylline or 5 X 10(-5)M glucagon. An adenylate cyclase particulate preparation shows that epinephrine decreases Km from 2mM to 0.6 MM and increases Vmax and the strength of interaction value (n) from 0.91 to 1.75."}
{"id": "PMID:187931", "title": "[Therapy of myasthenia (author's transl)].", "content": "The types of symptoms of myasthenia (Ossermann), specific problems of myasthenia therapy and the fundamental principles of treatment with cholinesterase inhibitors are discussed. In addition to the improved techniques in the observation room, the consistent performance of an immunosuppressive therapy usually leads to improvement of the prognosis of severe myasthenia. The principles of cortisone and Imurek therapy are commented on and the indication for thymectomy are discussed.", "contents": "[Therapy of myasthenia (author's transl)]. The types of symptoms of myasthenia (Ossermann), specific problems of myasthenia therapy and the fundamental principles of treatment with cholinesterase inhibitors are discussed. In addition to the improved techniques in the observation room, the consistent performance of an immunosuppressive therapy usually leads to improvement of the prognosis of severe myasthenia. The principles of cortisone and Imurek therapy are commented on and the indication for thymectomy are discussed."}
{"id": "PMID:187932", "title": "Methyl methanesulfonate mutagenesis of synchronized Chlamydomonas.", "content": "Methyl methanesulfonate (MMS) mutagenesis of Chlamydomonas reinhardtii at different stages of the synchronous cell-cycle revealed the following results. (1) Induction of phenotypically distinct Mendelian (nuclear), str-50 and non-Mendelian (chloroplast) str-500P, streptomycin resistant mutants was relatively high during the first portion of the cell-cycle when chloroplast DNA replication is known to occur. (2) A second and more pronounced interval of enhanced Mendelian, str-50 mutant induction was observed near the middle of the cell-cycle when the initial stages of nuclear DNA replication occur. Induction of non-Mendelian, str-500P mutants was inconsistent during this period. (3) The incidence of mutants from a second phenotypically distinct class of non-Mendelian streptomycin-resistant mutants (str-500D) was not increased over control levels at any stage of the cell-cycle examined. It is concluded that MMS, like N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), may not be the most suitable general mutagen for this alga because its enhanced mutagenesis of cells in the nuclear S phase could result in multiple closely linked mutations.", "contents": "Methyl methanesulfonate mutagenesis of synchronized Chlamydomonas. Methyl methanesulfonate (MMS) mutagenesis of Chlamydomonas reinhardtii at different stages of the synchronous cell-cycle revealed the following results. (1) Induction of phenotypically distinct Mendelian (nuclear), str-50 and non-Mendelian (chloroplast) str-500P, streptomycin resistant mutants was relatively high during the first portion of the cell-cycle when chloroplast DNA replication is known to occur. (2) A second and more pronounced interval of enhanced Mendelian, str-50 mutant induction was observed near the middle of the cell-cycle when the initial stages of nuclear DNA replication occur. Induction of non-Mendelian, str-500P mutants was inconsistent during this period. (3) The incidence of mutants from a second phenotypically distinct class of non-Mendelian streptomycin-resistant mutants (str-500D) was not increased over control levels at any stage of the cell-cycle examined. It is concluded that MMS, like N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), may not be the most suitable general mutagen for this alga because its enhanced mutagenesis of cells in the nuclear S phase could result in multiple closely linked mutations."}
{"id": "PMID:187933", "title": "Studies of factors influencing the mutagenicity of EMS in mice.", "content": "Three different routes of administration of ethyl methanesulphonate (EMS) (i.p., oral, i.t.) were compared for their relative efficiencies in the induction of dominant lethal effects. Included in the comparisons between oral and i.p. injections, was a preliminary study into the existence of strain differences in sensitivity to EMS between C3D2 F1 hybrid mice and strain DBA/2J mice. No route of administration dependent  effects were found between oral and i.p. injections regardless of the test animal used. I.t. injections of EMS did not induce dominant lethal effects. One treatment related strain difference was observed.", "contents": "Studies of factors influencing the mutagenicity of EMS in mice. Three different routes of administration of ethyl methanesulphonate (EMS) (i.p., oral, i.t.) were compared for their relative efficiencies in the induction of dominant lethal effects. Included in the comparisons between oral and i.p. injections, was a preliminary study into the existence of strain differences in sensitivity to EMS between C3D2 F1 hybrid mice and strain DBA/2J mice. No route of administration dependent  effects were found between oral and i.p. injections regardless of the test animal used. I.t. injections of EMS did not induce dominant lethal effects. One treatment related strain difference was observed."}
{"id": "PMID:187934", "title": "Quantitative evaluation of Epstein-Barr-virus-infected mononuclear peripheral blood leukocytes in infectious mononucleosis.", "content": "We devised a quantitative assay for Epstein-Barr-virus-infected mononuclear leukocytes (virocytes) to determine their prevalence in the blood of patients with acute-phase and convalescent-phase infectious mononucleosis and in healthy Epstein-Barr-virus-seropositive controls. Mononuclear peripheral blood leukocyte suspensions were tested for virus-determined cytoproliferative activity by cocultivation with human cord-cell indicator cultures. The highest levels of virocytes among circulating mononuclear leukocytes were found in the early acute phase of infectious mononucleosis (up to 0.05 per cent). Virocytemia decreased to levels comparable with those of healthy controls (less than 0.00001 per cent) by the third month after onset of infectious mononucleosis. These findings provide a quantitative profile of the course of the infection at cellular level and support existing evidence of the efficiency of immune control mechanisms in limiting Epstein-Barr-virus infection during the course of infectious mononucleosis.", "contents": "Quantitative evaluation of Epstein-Barr-virus-infected mononuclear peripheral blood leukocytes in infectious mononucleosis. We devised a quantitative assay for Epstein-Barr-virus-infected mononuclear leukocytes (virocytes) to determine their prevalence in the blood of patients with acute-phase and convalescent-phase infectious mononucleosis and in healthy Epstein-Barr-virus-seropositive controls. Mononuclear peripheral blood leukocyte suspensions were tested for virus-determined cytoproliferative activity by cocultivation with human cord-cell indicator cultures. The highest levels of virocytes among circulating mononuclear leukocytes were found in the early acute phase of infectious mononucleosis (up to 0.05 per cent). Virocytemia decreased to levels comparable with those of healthy controls (less than 0.00001 per cent) by the third month after onset of infectious mononucleosis. These findings provide a quantitative profile of the course of the infection at cellular level and support existing evidence of the efficiency of immune control mechanisms in limiting Epstein-Barr-virus infection during the course of infectious mononucleosis."}
{"id": "PMID:187944", "title": "Transformation by murine and feline sarcoma viruses specifically blocks binding of epidermal growth factor to cells.", "content": "Normal cells in culture have membrane receptors for epidermal growth factor (EGF); EGF stimulates cells to divide by binding to these receptors. Cells transformed by murine and feline sarcoma viruses rapidly lose the ability to bind EGF, whereas cells transformed by the DNA tumour viruses, polyoma and SV40, or infected with non-transforming RNA tumour viruses have normal levels of functional EGF receptors. The results suggest that a product of the sarcoma virus genome specifically changes cell EGF receptors; the sarcoma gene product may, then, be functionally related to EGF.", "contents": "Transformation by murine and feline sarcoma viruses specifically blocks binding of epidermal growth factor to cells. Normal cells in culture have membrane receptors for epidermal growth factor (EGF); EGF stimulates cells to divide by binding to these receptors. Cells transformed by murine and feline sarcoma viruses rapidly lose the ability to bind EGF, whereas cells transformed by the DNA tumour viruses, polyoma and SV40, or infected with non-transforming RNA tumour viruses have normal levels of functional EGF receptors. The results suggest that a product of the sarcoma virus genome specifically changes cell EGF receptors; the sarcoma gene product may, then, be functionally related to EGF."}
{"id": "PMID:187960", "title": "Alterations of dopaminergic neurotransmission after chronic morphine treatment: pre- and postjunctional studies in striatal tissue.", "content": "Repeated morphine administration reversed the acute effects of morphine in rats, e.g. catalepsy and akinesia, and induced symptoms suggesting an activation of dopaminergic mechanisms. In morphine-withdrawn rats, the potency or intrinsic activity of dopamine in stimulating the synthesis of cyclic AMP in striatal homogenates was not significantly altered. However, the K+-induced release of 14C-dopamine from striatal slices of morphine-withdrawn rats was significantly increased, compared with that from striatal slices of saline-treated controls. The results suggest that chronic morphine administration to rats increases the dopaminergic neurotransmission in brain by a pre-synaptic (prejunctional) mechanism, probably reflecting some kind of adaptation to the acute morphine action, which decreases the dopaminergic neurotransmission. The nigro-straital dopaminergic system, therefore, seems to be a good model to study acute morphine actions and mechanisms of morphine dependence at the cellular level.", "contents": "Alterations of dopaminergic neurotransmission after chronic morphine treatment: pre- and postjunctional studies in striatal tissue. Repeated morphine administration reversed the acute effects of morphine in rats, e.g. catalepsy and akinesia, and induced symptoms suggesting an activation of dopaminergic mechanisms. In morphine-withdrawn rats, the potency or intrinsic activity of dopamine in stimulating the synthesis of cyclic AMP in striatal homogenates was not significantly altered. However, the K+-induced release of 14C-dopamine from striatal slices of morphine-withdrawn rats was significantly increased, compared with that from striatal slices of saline-treated controls. The results suggest that chronic morphine administration to rats increases the dopaminergic neurotransmission in brain by a pre-synaptic (prejunctional) mechanism, probably reflecting some kind of adaptation to the acute morphine action, which decreases the dopaminergic neurotransmission. The nigro-straital dopaminergic system, therefore, seems to be a good model to study acute morphine actions and mechanisms of morphine dependence at the cellular level."}
{"id": "PMID:187961", "title": "Influence of papaverine derivatives on phosphodiesterase activity, cyclic 3',5'-AMP levels and relaxing effect on rabbit ileum.", "content": "The correlations between the relaxing effect of papaverine derivatives, inhibition of low Km-phosphodiesterase (cAMP-PDE = EC 3.1.4.17) activity and cyclic 3',5'-AMP (cAMP) levels in isolated rabbit ileum were investigated. There was a strong correlation between the relaxing effect, inhibition of PDE activity and cAMP content for eupaverine, ethylpapaverine and papaverine. Eupaverine was the most effective relaxing agent (I50 = 7.5 muM) and the most potent inhibitor of PDE activity (Ki = 0.6 muM), followed by ethylpapaverine (I50 = 10 muM;Ki 0.8 muM) and papaverine (I50 = 20 muM;Ki = 2 muM). In contrast, there was a strong relaxing effect (I50 = 6 muM) but only slight inhibition of PDE activity (Ki = 350 muM) by tetrahydropapaveroline (THP). The adenylate cyclase stimulating effect of THP which was shown by others is most likely the reason for comparatively higher cAMP levels, which were found to be elevated about seven times over basal levels of 0.35 nmoles/g wet weight, and effective relaxation. Relaxation could be induced by exogenously added cAMP (I50 = 45 muM) and dibutyryl-cAMP (I50 = 450 muM). Our results support the assumption that smooth muscle relaxation in rabbit ileum is mediated by cAMP. Some of these observations have been published in abstract form (Schulz and Berndt, 1972).", "contents": "Influence of papaverine derivatives on phosphodiesterase activity, cyclic 3',5'-AMP levels and relaxing effect on rabbit ileum. The correlations between the relaxing effect of papaverine derivatives, inhibition of low Km-phosphodiesterase (cAMP-PDE = EC 3.1.4.17) activity and cyclic 3',5'-AMP (cAMP) levels in isolated rabbit ileum were investigated. There was a strong correlation between the relaxing effect, inhibition of PDE activity and cAMP content for eupaverine, ethylpapaverine and papaverine. Eupaverine was the most effective relaxing agent (I50 = 7.5 muM) and the most potent inhibitor of PDE activity (Ki = 0.6 muM), followed by ethylpapaverine (I50 = 10 muM;Ki 0.8 muM) and papaverine (I50 = 20 muM;Ki = 2 muM). In contrast, there was a strong relaxing effect (I50 = 6 muM) but only slight inhibition of PDE activity (Ki = 350 muM) by tetrahydropapaveroline (THP). The adenylate cyclase stimulating effect of THP which was shown by others is most likely the reason for comparatively higher cAMP levels, which were found to be elevated about seven times over basal levels of 0.35 nmoles/g wet weight, and effective relaxation. Relaxation could be induced by exogenously added cAMP (I50 = 45 muM) and dibutyryl-cAMP (I50 = 450 muM). Our results support the assumption that smooth muscle relaxation in rabbit ileum is mediated by cAMP. Some of these observations have been published in abstract form (Schulz and Berndt, 1972)."}
{"id": "PMID:187962", "title": "Dopaminergic stimulants and cyclic nucleotides in mouse brain. Effects of dopaminergic antagonists, cholinolytics, and GABA agonists.", "content": "The effects of dopaminergic stimulants on the cyclic GMP content in the medial forebrain and the cerebellum were studied in mice pretreated with dopaminergic antagonists, cholinolytics and agents enhancing GABAergic transmission. Low doses of butyrophenones (haloperidol and spiroperidol) inhibited the rise in cyclic GMP levels and the stereotyped behaviour induced by amphetamine, but were without effect on the same biochemical and behavioural changes elicited by apomorphine. Higher doses effectively blocked the rise in cyclic GMP levels and the stereotyped behaviour elicited by both drugs. These findings suggest that low doses of the dopaminergic antagonists may predominantly act by interfering with the release of dopamine from presynaptic stores, while high doses may act by blockade of the postsynaptic dopaminergic receptor. The rise in cerebellar cyclic GMP levels elicited by dopaminergic stimulants appears not to involve cholinergic transmission, since atropine did not block the effects of the dopaminergic stimulants. Enhancement of GABAergic transmission by diazepam or aminooxyacetic acid antagonized the rise in cerebellar cyclic GMP content induced by the dopaminergic stimulants, but was without effect on the cyclic GMP content in the medial forebrain. Cyclic AMP levels were not affected by any of the drugs in both parts of the brain.", "contents": "Dopaminergic stimulants and cyclic nucleotides in mouse brain. Effects of dopaminergic antagonists, cholinolytics, and GABA agonists. The effects of dopaminergic stimulants on the cyclic GMP content in the medial forebrain and the cerebellum were studied in mice pretreated with dopaminergic antagonists, cholinolytics and agents enhancing GABAergic transmission. Low doses of butyrophenones (haloperidol and spiroperidol) inhibited the rise in cyclic GMP levels and the stereotyped behaviour induced by amphetamine, but were without effect on the same biochemical and behavioural changes elicited by apomorphine. Higher doses effectively blocked the rise in cyclic GMP levels and the stereotyped behaviour elicited by both drugs. These findings suggest that low doses of the dopaminergic antagonists may predominantly act by interfering with the release of dopamine from presynaptic stores, while high doses may act by blockade of the postsynaptic dopaminergic receptor. The rise in cerebellar cyclic GMP levels elicited by dopaminergic stimulants appears not to involve cholinergic transmission, since atropine did not block the effects of the dopaminergic stimulants. Enhancement of GABAergic transmission by diazepam or aminooxyacetic acid antagonized the rise in cerebellar cyclic GMP content induced by the dopaminergic stimulants, but was without effect on the cyclic GMP content in the medial forebrain. Cyclic AMP levels were not affected by any of the drugs in both parts of the brain."}
{"id": "PMID:187963", "title": "Effects of methacholine, histamine and atropine on pulmonary guanosine-3', 5'-monophosphate levels in hypersensitive mice.", "content": "Pulmonary levels of cGMP and cAMP in mice sensitized to methacholine and histamine with B. pertussis were examined to determine whether sensitization could be the result of an alteration in the metabolism of these cyclic nucleotides. The results presented show that in sensitized mice, methacholine raised cGMP to levels that were about double those produced without sensitization. In analogous experiments, histamine raised cGMP by approximately 100% in sensitized mice without producing significant increases in nonsensitized groups. Atropine completely blocked the cGMP rises produced by methacholine but did not eliminate those produced by histamine, thus indicating that cholinergic, but not the histaminergic elevation of cGMP involves activation of muscarinic receptors. The influence of pertussis on cAMP appeared to be opposite in direction from cGMP, i.e., a small but significant drop in cAMP levels was found following methacholine administration to sensitized, but not to nonsensitized mice. It was concluded that pertussis sensitization increases the responsiveness of the pulmonary guanylate cyclase-cGMP system to methacholine and histamine, and that the altered patterns of cGMP accumulation may contribute to the biochemical mechanism of sensitization.", "contents": "Effects of methacholine, histamine and atropine on pulmonary guanosine-3', 5'-monophosphate levels in hypersensitive mice. Pulmonary levels of cGMP and cAMP in mice sensitized to methacholine and histamine with B. pertussis were examined to determine whether sensitization could be the result of an alteration in the metabolism of these cyclic nucleotides. The results presented show that in sensitized mice, methacholine raised cGMP to levels that were about double those produced without sensitization. In analogous experiments, histamine raised cGMP by approximately 100% in sensitized mice without producing significant increases in nonsensitized groups. Atropine completely blocked the cGMP rises produced by methacholine but did not eliminate those produced by histamine, thus indicating that cholinergic, but not the histaminergic elevation of cGMP involves activation of muscarinic receptors. The influence of pertussis on cAMP appeared to be opposite in direction from cGMP, i.e., a small but significant drop in cAMP levels was found following methacholine administration to sensitized, but not to nonsensitized mice. It was concluded that pertussis sensitization increases the responsiveness of the pulmonary guanylate cyclase-cGMP system to methacholine and histamine, and that the altered patterns of cGMP accumulation may contribute to the biochemical mechanism of sensitization."}
{"id": "PMID:187964", "title": "Comparative studies on isolated rat hepatocytes and AS-30D hepatoma cells with leucocidin from Pseudomonas aeruginosa.", "content": "Leucocidin, one of the cytotoxic principles of Pseudomonas aeruginosa induces potassium loss and swelling in isolated hepatocytes and in AS-30D ascites hepatoma cells in a dose and time dependent manner. Hepatoma cells are more sensitive than normal hepatocytes. As shown by scanning electron microscopy the volume increase of both types of cells is accompanied by disappearance of microvilli. In contrast to phalloidin poisoning no protrusions were formed when the cells were exposed to leucocidin under isotonic conditions.", "contents": "Comparative studies on isolated rat hepatocytes and AS-30D hepatoma cells with leucocidin from Pseudomonas aeruginosa. Leucocidin, one of the cytotoxic principles of Pseudomonas aeruginosa induces potassium loss and swelling in isolated hepatocytes and in AS-30D ascites hepatoma cells in a dose and time dependent manner. Hepatoma cells are more sensitive than normal hepatocytes. As shown by scanning electron microscopy the volume increase of both types of cells is accompanied by disappearance of microvilli. In contrast to phalloidin poisoning no protrusions were formed when the cells were exposed to leucocidin under isotonic conditions."}
{"id": "PMID:187965", "title": "Some pharmacological properties of the false cholinergic transmitter acetylpyrrolidinecholine and its precursor pyrrolidinecholine.", "content": "The acetylchline analogue acetylpyrrolidinecholine as well as the choline analogue pyrrolidinecholine were synthesized and the cholinergic properties of both substances were investigated on the guinea-pig ileum, rat blood pressure and frog rectus abdominis muscle. Acetylpyrrolidinecholine was 3-5 times less potent than acetylcholine on the three preparations tested. The dose-response curves to acetylpyrrolidinecholine were shifted to the right in a parallel manner by atropine and (+)-tubocurarine. The dissociation constants for atropine and (+)-tubocurarine obtained with acetylpyrrolidinecholine as agonist were not different from those obtained with acetylcholine. This indicates that acetylpyrrolidinecholine specifically stimulates muscarine and nicotine receptors. Eserine potentiated the effects of acetylcholine more than those of acetylpyrrolidinecholine. Pyrrolidinecholine was only a weak agonist on the guinea-pig ileum. It caused a rise of rat blood pressure in doses higher than 10 mumol per rat. Neuromuscular transmission of the phrenic nerve-diaphragm preparation of the rat was not impaired during a 150 min incubation period with 1 mM pyrrolidinecholine. It is suggested that the possible formation and release of acetylpyrrolidinecholine as a false cholinergic transmitter does not modify neuromuscular transmission in skeletal muscle.", "contents": "Some pharmacological properties of the false cholinergic transmitter acetylpyrrolidinecholine and its precursor pyrrolidinecholine. The acetylchline analogue acetylpyrrolidinecholine as well as the choline analogue pyrrolidinecholine were synthesized and the cholinergic properties of both substances were investigated on the guinea-pig ileum, rat blood pressure and frog rectus abdominis muscle. Acetylpyrrolidinecholine was 3-5 times less potent than acetylcholine on the three preparations tested. The dose-response curves to acetylpyrrolidinecholine were shifted to the right in a parallel manner by atropine and (+)-tubocurarine. The dissociation constants for atropine and (+)-tubocurarine obtained with acetylpyrrolidinecholine as agonist were not different from those obtained with acetylcholine. This indicates that acetylpyrrolidinecholine specifically stimulates muscarine and nicotine receptors. Eserine potentiated the effects of acetylcholine more than those of acetylpyrrolidinecholine. Pyrrolidinecholine was only a weak agonist on the guinea-pig ileum. It caused a rise of rat blood pressure in doses higher than 10 mumol per rat. Neuromuscular transmission of the phrenic nerve-diaphragm preparation of the rat was not impaired during a 150 min incubation period with 1 mM pyrrolidinecholine. It is suggested that the possible formation and release of acetylpyrrolidinecholine as a false cholinergic transmitter does not modify neuromuscular transmission in skeletal muscle."}
{"id": "PMID:187966", "title": "In vivo blocking of SV40 virus-induced antitumor resistance by Syrian hamster sera from early stages of primary SV40 carcinogenesis.", "content": "The blocking of specific SV40-induced resistance of hamsters by the sera collected from 12 individual hamsters infected with SV40 when newborn was studied at different periods of primary virus-induced carcinogenesis. The serum samples were collected at the following periods of primary carcinogenesis: during the latent period (60 days after virus inoculation), at the day of primary tumor appearance, and 19-36 and 45-57 days after primary tumor appearance. For detection of the blocking activity of the collected sera the cells of transplantable SV40 test-tumor were pretreated in vitro with these sera and with control normal hamster sera, and then used for challenge in vivo in SV40-immunized and normal hamsters. With the use of such method, as a rule, no blocking activity of the serum samples collected at any time after the tumor appearance was observed. However, the sera obtained from 7 out of 12 of these hamsters during the latent period significantly decreased the resistance index of animals challenged in transplantation test with the serum pretreated tumor cells. Possible explanations of these findings are discussed.", "contents": "In vivo blocking of SV40 virus-induced antitumor resistance by Syrian hamster sera from early stages of primary SV40 carcinogenesis. The blocking of specific SV40-induced resistance of hamsters by the sera collected from 12 individual hamsters infected with SV40 when newborn was studied at different periods of primary virus-induced carcinogenesis. The serum samples were collected at the following periods of primary carcinogenesis: during the latent period (60 days after virus inoculation), at the day of primary tumor appearance, and 19-36 and 45-57 days after primary tumor appearance. For detection of the blocking activity of the collected sera the cells of transplantable SV40 test-tumor were pretreated in vitro with these sera and with control normal hamster sera, and then used for challenge in vivo in SV40-immunized and normal hamsters. With the use of such method, as a rule, no blocking activity of the serum samples collected at any time after the tumor appearance was observed. However, the sera obtained from 7 out of 12 of these hamsters during the latent period significantly decreased the resistance index of animals challenged in transplantation test with the serum pretreated tumor cells. Possible explanations of these findings are discussed."}
{"id": "PMID:187967", "title": "Varicella-zoster antibodies in patients with Hodgkin's disease.", "content": "In an endeavour to find an explanation for th raised incidence of herpes zoster in hemoblastoses, serum samples of 50 patients with histologically confirmed Hodgkin's disease and 80 control sera of normal persons of similar age groups were tested for the presenchods of indirect hemagglutination (IH), complement fixation (CF), and immunodiffusion (ID). The geometric mean titer of IH antibodies and the rate of positive ID results were significantly higher in the patients' group. The geometric mean titers of CF antibodies did not differ significantly in the two groups. A certain correlation between serological results and the histological type of Hodgkin's disease was found, but it was not statistically significant. No other correlation of serological results with clinical data was ascertained.", "contents": "Varicella-zoster antibodies in patients with Hodgkin's disease. In an endeavour to find an explanation for th raised incidence of herpes zoster in hemoblastoses, serum samples of 50 patients with histologically confirmed Hodgkin's disease and 80 control sera of normal persons of similar age groups were tested for the presenchods of indirect hemagglutination (IH), complement fixation (CF), and immunodiffusion (ID). The geometric mean titer of IH antibodies and the rate of positive ID results were significantly higher in the patients' group. The geometric mean titers of CF antibodies did not differ significantly in the two groups. A certain correlation between serological results and the histological type of Hodgkin's disease was found, but it was not statistically significant. No other correlation of serological results with clinical data was ascertained."}
{"id": "PMID:187968", "title": "Histochemistry of oxidoreductases, enzymatic polymorphism and anaplasia of neuroectodermal tumors.", "content": "Oxidoreductases were studied histochemically in 162 cases of neuroectodermal tumors. In order of decreasing activity in the cytoplasma these enzymes could be arranged as follows: NADH diaphorase, lactate dehydrogenase, NADPH diaphorase, glutamate dehydrogenase, glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase. The weak activity of Krebs cycle enzymes and the relatively strong activity of other oxidoreductases, particularly of lactate dehydrogenase, permits to conclude that glycolysis prevails over oxidative processes in neuroectodermal tumor cells. But this should not be interpreted as a decrease of the Krebs cycle enzymes in astrocytoma and oligodendroglioma cells as compared with their parent cells because the latter themselves display a weak activity of these enzymes. A real decrease of Krebs cycle enzyme activity was established only for tumors, the parent cells of which are characterized by a strong (in choroid-papillomas) or moderate (in ependymomas) activity of these enzymes. Many neuroectodermal tumors, in particular those of astrocytic origin, demonstrate a certain correlation between the amount of cytoplasm and oxidoreductase activity. This results in enzymatic polymorphism of the tumor tissue. A certain similarity was established of the oxidoreductase activity in tumor cells and in reactive hypertophic astrocytes. This indicates that both tumor cells and reactive astrocytes may in certain conditions utilize similar mechanisms of increased metabolism. The oxidoreductase activity correlates not with the grade of anaplasia but with different directions of anaplasia reflected in different variants of neuroectodermal tumors. The concept \"anaplasia\" includes not only certain degrees of dedifferentiation of tumor cells but, as it has been shown histochemically, also an increase of metabolic processes in the tumor cell cytoplasma.", "contents": "Histochemistry of oxidoreductases, enzymatic polymorphism and anaplasia of neuroectodermal tumors. Oxidoreductases were studied histochemically in 162 cases of neuroectodermal tumors. In order of decreasing activity in the cytoplasma these enzymes could be arranged as follows: NADH diaphorase, lactate dehydrogenase, NADPH diaphorase, glutamate dehydrogenase, glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase. The weak activity of Krebs cycle enzymes and the relatively strong activity of other oxidoreductases, particularly of lactate dehydrogenase, permits to conclude that glycolysis prevails over oxidative processes in neuroectodermal tumor cells. But this should not be interpreted as a decrease of the Krebs cycle enzymes in astrocytoma and oligodendroglioma cells as compared with their parent cells because the latter themselves display a weak activity of these enzymes. A real decrease of Krebs cycle enzyme activity was established only for tumors, the parent cells of which are characterized by a strong (in choroid-papillomas) or moderate (in ependymomas) activity of these enzymes. Many neuroectodermal tumors, in particular those of astrocytic origin, demonstrate a certain correlation between the amount of cytoplasm and oxidoreductase activity. This results in enzymatic polymorphism of the tumor tissue. A certain similarity was established of the oxidoreductase activity in tumor cells and in reactive hypertophic astrocytes. This indicates that both tumor cells and reactive astrocytes may in certain conditions utilize similar mechanisms of increased metabolism. The oxidoreductase activity correlates not with the grade of anaplasia but with different directions of anaplasia reflected in different variants of neuroectodermal tumors. The concept \"anaplasia\" includes not only certain degrees of dedifferentiation of tumor cells but, as it has been shown histochemically, also an increase of metabolic processes in the tumor cell cytoplasma."}
{"id": "PMID:187969", "title": "A clinico-pathological study on the correlation of immunosuppression and multiple primary malignant neoplasmas.", "content": "At present it is obvious that the incidence of second malignancies in patients with malignant diseases increases after prolonged treatment with immunosuppressive, or antineoplastic agents. The occurrence of such additional malignant diseases was analysed in our five-years autopsy material. During this period 7670 autopsies were performed. Malignant diseases were observed in 1707 cases (22.1%) and among them in 58 cases were proved multiple primary malignant neoplasms (3.3%). The average time between the occurrence of initial and second tumors was 29 months. The frequency of second tumors in patients with leukemias (mainly chronic lymphocytic leukemia) were four times higher than in patients with tumors of epithelial origin. Hepatocarcinomas arose in cirrhotic livers and astrocytomas were often followed by new malignancies. In consequence of successfully applied surgical, radiological and combined immunosuppressive, antineoplastic therapy the survival of cancer patients lengthened, so among different side-effects of the used therapy the oncogenesis cannot be left out of account. The danger of subsequent malignant tumors makes it imperative that immunosuppression should only be applied when strictly indicated.", "contents": "A clinico-pathological study on the correlation of immunosuppression and multiple primary malignant neoplasmas. At present it is obvious that the incidence of second malignancies in patients with malignant diseases increases after prolonged treatment with immunosuppressive, or antineoplastic agents. The occurrence of such additional malignant diseases was analysed in our five-years autopsy material. During this period 7670 autopsies were performed. Malignant diseases were observed in 1707 cases (22.1%) and among them in 58 cases were proved multiple primary malignant neoplasms (3.3%). The average time between the occurrence of initial and second tumors was 29 months. The frequency of second tumors in patients with leukemias (mainly chronic lymphocytic leukemia) were four times higher than in patients with tumors of epithelial origin. Hepatocarcinomas arose in cirrhotic livers and astrocytomas were often followed by new malignancies. In consequence of successfully applied surgical, radiological and combined immunosuppressive, antineoplastic therapy the survival of cancer patients lengthened, so among different side-effects of the used therapy the oncogenesis cannot be left out of account. The danger of subsequent malignant tumors makes it imperative that immunosuppression should only be applied when strictly indicated."}
{"id": "PMID:187970", "title": "The levels of NAD and NADH in blood of patients with cancer.", "content": "The levels of nicotinamide adenine dinucleotide (NAD) and NADH in blood of patients with cancer in various stages of development as well as their modification after glucose administration were determined in 188 respectively 77 cases. NAD was significantly decreased in patients with cervix and breast carcinoma but unaltered in patients with metastatic cancers (and lung carcinoma) comparatively with healthy subjects. At 48 hours after i.v. administration of glucose, NAD increased significantly in patients with cervix carcinoma but was unaltered in patients with metastatic cancers (an lung carcinoma). NADH in both cases has given little conclusive results.", "contents": "The levels of NAD and NADH in blood of patients with cancer. The levels of nicotinamide adenine dinucleotide (NAD) and NADH in blood of patients with cancer in various stages of development as well as their modification after glucose administration were determined in 188 respectively 77 cases. NAD was significantly decreased in patients with cervix and breast carcinoma but unaltered in patients with metastatic cancers (and lung carcinoma) comparatively with healthy subjects. At 48 hours after i.v. administration of glucose, NAD increased significantly in patients with cervix carcinoma but was unaltered in patients with metastatic cancers (an lung carcinoma). NADH in both cases has given little conclusive results."}
{"id": "PMID:187971", "title": "Nonspecific immunosuppression and expression of avian myeloblastosis virus (BAI strain A).", "content": "Chickens were treated with cyclophosphamide in order to induce nonspecific immunosuppression. Treated and untreated animals were injected with avian myeloblastosis virus (AMV) or myeloblasts at the age when a pronounced resistance to the disease is observed. Chickens treated with cyclophosphamide and then challenged with AMV developed acute myeloblastic leukemia in 70 percent. Similarly treated chickens transplanted with fresh AMV producing myeloblasts exhibited 30 percent incidence of myeloblastosis. In contrast, the control animals without treatment showed no myeloblastosis either after myeloblasts application or AMV injection. These results have shown that nonspecific immunosuppression by cyclophosphamide treatment strongly affects the expression of AMV in age-resistant chickens.", "contents": "Nonspecific immunosuppression and expression of avian myeloblastosis virus (BAI strain A). Chickens were treated with cyclophosphamide in order to induce nonspecific immunosuppression. Treated and untreated animals were injected with avian myeloblastosis virus (AMV) or myeloblasts at the age when a pronounced resistance to the disease is observed. Chickens treated with cyclophosphamide and then challenged with AMV developed acute myeloblastic leukemia in 70 percent. Similarly treated chickens transplanted with fresh AMV producing myeloblasts exhibited 30 percent incidence of myeloblastosis. In contrast, the control animals without treatment showed no myeloblastosis either after myeloblasts application or AMV injection. These results have shown that nonspecific immunosuppression by cyclophosphamide treatment strongly affects the expression of AMV in age-resistant chickens."}
{"id": "PMID:187972", "title": "Infection of human embryo cells with avian sarcoma virus B77 in vitro.", "content": "Human embryo cells were infected with avian sarcoma virus B77--Hu(B77). The virus genome was detected in the Hu(B77) cells during subsequent cell passages in the uncloned cells as well as in single-cell clones. Despite the presence of the virus genome in cells, the growth properties did not differ from uninfected cells. The Hu(B77) cells did not reveal the transformed phenotype in vitro.", "contents": "Infection of human embryo cells with avian sarcoma virus B77 in vitro. Human embryo cells were infected with avian sarcoma virus B77--Hu(B77). The virus genome was detected in the Hu(B77) cells during subsequent cell passages in the uncloned cells as well as in single-cell clones. Despite the presence of the virus genome in cells, the growth properties did not differ from uninfected cells. The Hu(B77) cells did not reveal the transformed phenotype in vitro."}
{"id": "PMID:187973", "title": "An in vitro study of the oncogenic effects of two variants of avian sarcoma virus B77 on rat embryonal fibroblasts.", "content": "Two variants of avian sarcoma virus B77 have been tested for their heteroinductive oncogenic in vitro effects on rat embryonal cells. Variant 22-B77V belonging to subgroup B, had been cultured for a long time exclusively on its original host, i.e. on chicks, before being used in the study. This variant of B77V yielded negative results in repeated experiments on rat cells. Variant 55-B77V belonging to subgroup C and which had been made to pass through rat cells, caused a malignant transformation in the latter. The resultant type of this interaction were virus-producing tumorous cells (designated LWF B55). This study present some of the basic characteristics of these cells.", "contents": "An in vitro study of the oncogenic effects of two variants of avian sarcoma virus B77 on rat embryonal fibroblasts. Two variants of avian sarcoma virus B77 have been tested for their heteroinductive oncogenic in vitro effects on rat embryonal cells. Variant 22-B77V belonging to subgroup B, had been cultured for a long time exclusively on its original host, i.e. on chicks, before being used in the study. This variant of B77V yielded negative results in repeated experiments on rat cells. Variant 55-B77V belonging to subgroup C and which had been made to pass through rat cells, caused a malignant transformation in the latter. The resultant type of this interaction were virus-producing tumorous cells (designated LWF B55). This study present some of the basic characteristics of these cells."}
{"id": "PMID:187974", "title": "Growth characteristics and tumorigenicity of long-term cultures of the rat RBA myelogenous leukemia.", "content": "A continuous cell line, RBA-BC, has been derived from the buffy coat of heparinized blood of a Sprague--Dawley rat with developed RBA myeloblastosis. Separations of myeloblasts from the RBA-BC cell line was accomplished by velocity sedimentation in Verografin density gradients. The cells were monitored during long-term culture by generation time analysis. Cytochemical studies revealed the myelogenous type of RBA leukemia.", "contents": "Growth characteristics and tumorigenicity of long-term cultures of the rat RBA myelogenous leukemia. A continuous cell line, RBA-BC, has been derived from the buffy coat of heparinized blood of a Sprague--Dawley rat with developed RBA myeloblastosis. Separations of myeloblasts from the RBA-BC cell line was accomplished by velocity sedimentation in Verografin density gradients. The cells were monitored during long-term culture by generation time analysis. Cytochemical studies revealed the myelogenous type of RBA leukemia."}
{"id": "PMID:187977", "title": "Possible role of dopamine in diethylstilbestrol-elicited accumulation of cyclic AMP in incubated male rat hypothalamus.", "content": "Pimozide and haloperidol, the dopaminergic antagonists, have been shown to effectively block diethylstilbestrol (DES)-elicited [3H] adenosine 3', 5'-monophosphate (cAMP) accumulation in incubated hypothalami from immature male rats. Several noradrenergic antagonists (i.e. propranolol, MJ-1999 and phenoxybenzamine) failed to reduce [3H]cAMP levels significantly. Pimozide was found to be more specific than haloperidol as it did not effect norepinephrine (NE)-elicited formation of [3H]cAMP, while the latter blocker caused a 48% reduction of the stimulation by NE. Pimozide was also more potent than haloperidol in inhibiting DES-stimulated [3H]cAMP formation. It can be inferred from these data that as a result of DES-receptor interaction dopamine (DA) is released and in turn activates DA-sensitive adenylate cyclase in the hypothalamus.", "contents": "Possible role of dopamine in diethylstilbestrol-elicited accumulation of cyclic AMP in incubated male rat hypothalamus. Pimozide and haloperidol, the dopaminergic antagonists, have been shown to effectively block diethylstilbestrol (DES)-elicited [3H] adenosine 3', 5'-monophosphate (cAMP) accumulation in incubated hypothalami from immature male rats. Several noradrenergic antagonists (i.e. propranolol, MJ-1999 and phenoxybenzamine) failed to reduce [3H]cAMP levels significantly. Pimozide was found to be more specific than haloperidol as it did not effect norepinephrine (NE)-elicited formation of [3H]cAMP, while the latter blocker caused a 48% reduction of the stimulation by NE. Pimozide was also more potent than haloperidol in inhibiting DES-stimulated [3H]cAMP formation. It can be inferred from these data that as a result of DES-receptor interaction dopamine (DA) is released and in turn activates DA-sensitive adenylate cyclase in the hypothalamus."}
{"id": "PMID:187978", "title": "The effects of cholinomimetic drugs and atropine on ACTH release.", "content": "Acetylcholine (1 and 50 mug), carbamylcholine (1 and 10 mug), and oxotremorine (10 mug) were infused into the 3rd ventricle of rats with deafferented medial basal hypothalamus (MBH); infusions failed to stimulate ACTH release as shown by the plasma corticosterone level. Implants of an atropine-fluorescein mixture (200-250 mug) inhibited the stress-induced rise of plasma corticosterone only when dye from the implant stained large portions of the median eminence and the basal hypothalamus. Atropine implants near the electrodes inhibited the rise in plasma corticosterone usually produced by electrical stimulation in the anterior hypothalamus. Atropine crystals or a 2% atropine sulphate solution placed on the median eminence blocked conduction of action potential in the hypothalamo neurohypophyseal and tubero-infundibular pathways. The evidence will be discussed for and against the participation of a cholinergic synapse (in the MBH) that activates ACTH release after stressful neural stimuli.", "contents": "The effects of cholinomimetic drugs and atropine on ACTH release. Acetylcholine (1 and 50 mug), carbamylcholine (1 and 10 mug), and oxotremorine (10 mug) were infused into the 3rd ventricle of rats with deafferented medial basal hypothalamus (MBH); infusions failed to stimulate ACTH release as shown by the plasma corticosterone level. Implants of an atropine-fluorescein mixture (200-250 mug) inhibited the stress-induced rise of plasma corticosterone only when dye from the implant stained large portions of the median eminence and the basal hypothalamus. Atropine implants near the electrodes inhibited the rise in plasma corticosterone usually produced by electrical stimulation in the anterior hypothalamus. Atropine crystals or a 2% atropine sulphate solution placed on the median eminence blocked conduction of action potential in the hypothalamo neurohypophyseal and tubero-infundibular pathways. The evidence will be discussed for and against the participation of a cholinergic synapse (in the MBH) that activates ACTH release after stressful neural stimuli."}
{"id": "PMID:187980", "title": "The temporal and periodic organization of REM eye movements in mental retardation.", "content": "Time trends and periodic cycles in REM sleep eye movements were examined in 6 functional and 6 mongoloid adolescent retardates. Both groups of subjects showed approximately equal percentages of linear trends, quadratic trends, linear and quadratic trends, and absence of trend. The eye movement time-series were subject to an orthogonal spectral analysis. In both groups of subjects, peak spectral estimates generally occurred at 10.6- or 21.3-min periods. Following this, the eye movements of the longest REM periods (and one long period of pre-sleep wakefulness) were subject to a least-squares spectral analysis. This analysis yielded estimates ranging from 22 to 44 min. Eye movements lacked the ultradian organization previously reported for eye movements of normal subjects. These results imply that the ultradian organization of REM sleep and the ultradian organization of eye movements may be independent.", "contents": "The temporal and periodic organization of REM eye movements in mental retardation. Time trends and periodic cycles in REM sleep eye movements were examined in 6 functional and 6 mongoloid adolescent retardates. Both groups of subjects showed approximately equal percentages of linear trends, quadratic trends, linear and quadratic trends, and absence of trend. The eye movement time-series were subject to an orthogonal spectral analysis. In both groups of subjects, peak spectral estimates generally occurred at 10.6- or 21.3-min periods. Following this, the eye movements of the longest REM periods (and one long period of pre-sleep wakefulness) were subject to a least-squares spectral analysis. This analysis yielded estimates ranging from 22 to 44 min. Eye movements lacked the ultradian organization previously reported for eye movements of normal subjects. These results imply that the ultradian organization of REM sleep and the ultradian organization of eye movements may be independent."}
{"id": "PMID:187982", "title": "Extensive calcification in a tumor of the glomus jugulare.", "content": "Extensive calcification in the intracranial portion of a glomus jugulare tumor is reported. This finding has not been reported previously in the literature. The patient probably was afflicted with this process for many years and presented with a subarachnoid hemorrhage. The combination of this tumor with subarachnoid hemorrhage is rare.", "contents": "Extensive calcification in a tumor of the glomus jugulare. Extensive calcification in the intracranial portion of a glomus jugulare tumor is reported. This finding has not been reported previously in the literature. The patient probably was afflicted with this process for many years and presented with a subarachnoid hemorrhage. The combination of this tumor with subarachnoid hemorrhage is rare."}
{"id": "PMID:187987", "title": "[Controlled trial with ACTH and corticosteroids in patients with cholestatic viral hepatitis].", "content": "Comparison was made between synthetic ACTH (tetracosactide), betamethasone and a normal paradigm (dietary management with glucose solutions, detoxicants and vitamins) over a period at least of 21 days in 27 patients with cholostatic viral hepatitis. Assessment of the clinical and laboratory parameters by means of both covariance and multivariance analysis showed that hormonal therapy offered no significant advantages with respect to the basic treatment protocol.", "contents": "[Controlled trial with ACTH and corticosteroids in patients with cholestatic viral hepatitis]. Comparison was made between synthetic ACTH (tetracosactide), betamethasone and a normal paradigm (dietary management with glucose solutions, detoxicants and vitamins) over a period at least of 21 days in 27 patients with cholostatic viral hepatitis. Assessment of the clinical and laboratory parameters by means of both covariance and multivariance analysis showed that hormonal therapy offered no significant advantages with respect to the basic treatment protocol."}
{"id": "PMID:187990", "title": "Serum 17 alpha-hydroxyprogesterone in patients with gestational trophoblastic neoplasms.", "content": "Serum 17alpha-hydroxprogesterone (17-OHP), progesterone (P), and human chorionic gonadotropin (hCG) levels were measured by specific radioimmunoassay in 19 patients undergoing laparoscopy or laparotomy with either unevacuated molar pregnancy or nonmetastatic gestational trophoblastic neoplasms (GTN), in 10 normal pregnant patients at equivalent gestational age (7-21 weeks), and in 4 patients with metastaic GTN following hysterectomy and bilateral salpingo-oophorectomy. All patients with theca lutein cysts had significantly elevated serum 17-OHP levels compared to those in 1) normal pregnancy, 2) patients with GTN and normal-size ovaries, 3) patients with metastatic GTN in the absence of ovaries (P less than 0.02). Levels of serum 17-OHP but not P correlated with the degree of ovarian enlargement (r = 0.87, P less than 0.05). Serum P concentrations in patients with theca lutein cysts, although higher than the levels in cases of GTN with normal-size ovaries, were not significantly different from the levels in normal pregnancy (P greater than 0.05). Serum hCG levels in patients with theca lutein cysts, though higher than the normal pregnancy levels (P less than 0.05), were not significantly different from those in cases of GTN with normal-size ovaries and GTN without ovaries (P greater than 0.05). Under the conditions studied, no correlation was observed between serum hCG and P levels in our cases of GTN. Increased serum 17-OHP level in a patient with GTN suggests the presence of theca lutein cysts.", "contents": "Serum 17 alpha-hydroxyprogesterone in patients with gestational trophoblastic neoplasms. Serum 17alpha-hydroxprogesterone (17-OHP), progesterone (P), and human chorionic gonadotropin (hCG) levels were measured by specific radioimmunoassay in 19 patients undergoing laparoscopy or laparotomy with either unevacuated molar pregnancy or nonmetastatic gestational trophoblastic neoplasms (GTN), in 10 normal pregnant patients at equivalent gestational age (7-21 weeks), and in 4 patients with metastaic GTN following hysterectomy and bilateral salpingo-oophorectomy. All patients with theca lutein cysts had significantly elevated serum 17-OHP levels compared to those in 1) normal pregnancy, 2) patients with GTN and normal-size ovaries, 3) patients with metastatic GTN in the absence of ovaries (P less than 0.02). Levels of serum 17-OHP but not P correlated with the degree of ovarian enlargement (r = 0.87, P less than 0.05). Serum P concentrations in patients with theca lutein cysts, although higher than the levels in cases of GTN with normal-size ovaries, were not significantly different from the levels in normal pregnancy (P greater than 0.05). Serum hCG levels in patients with theca lutein cysts, though higher than the normal pregnancy levels (P less than 0.05), were not significantly different from those in cases of GTN with normal-size ovaries and GTN without ovaries (P greater than 0.05). Under the conditions studied, no correlation was observed between serum hCG and P levels in our cases of GTN. Increased serum 17-OHP level in a patient with GTN suggests the presence of theca lutein cysts."}
{"id": "PMID:187991", "title": "Effect of treatment with estrogen conjugates on endogenous plasma steroids.", "content": "Plasma dehydroenpiandrosterone sulfate (DS), androstenedione (A2), estrone plus estradiol (E1+2) and estriol (E3) were measured in women treated with conjugated estrogens and controls. Plasma DS, A2, and E1+2 levels were higher in the premenopausal controls than in the untreated postmenopausal women; E3 levels were below the sensitivity of the assay. Estrogen conjugates, 1.25 mg or 2.5 mg daily, increased plasma E1+2 to levels similar to those in premenopausal untreated women, and E3 became readily assayable. A 0.625-mg dose increased the level of E3 without affecting E1+2; consequently, the plasma E3/E1+2 ratio was elevated. It is concluded that at the lowest dose 16 alpha-hydroxylase activity, perhaps by substrate induction, is sufficient for the exogenous esogenous estrogens to be largely metabolized to E3. Estrogen conjugates had no detectable effect on plasma DS or A2.", "contents": "Effect of treatment with estrogen conjugates on endogenous plasma steroids. Plasma dehydroenpiandrosterone sulfate (DS), androstenedione (A2), estrone plus estradiol (E1+2) and estriol (E3) were measured in women treated with conjugated estrogens and controls. Plasma DS, A2, and E1+2 levels were higher in the premenopausal controls than in the untreated postmenopausal women; E3 levels were below the sensitivity of the assay. Estrogen conjugates, 1.25 mg or 2.5 mg daily, increased plasma E1+2 to levels similar to those in premenopausal untreated women, and E3 became readily assayable. A 0.625-mg dose increased the level of E3 without affecting E1+2; consequently, the plasma E3/E1+2 ratio was elevated. It is concluded that at the lowest dose 16 alpha-hydroxylase activity, perhaps by substrate induction, is sufficient for the exogenous esogenous estrogens to be largely metabolized to E3. Estrogen conjugates had no detectable effect on plasma DS or A2."}
{"id": "PMID:187992", "title": "Synergistic bacterial gangrene following abdominal hysterectomy.", "content": "A case of synergistic bacterial gangrene occurring after abdominal hysterectomy in a 43-year-old patient is presented. After multiple debridement procedures and porcine grafts, the patient responded satisfactorily and eventually recovered.", "contents": "Synergistic bacterial gangrene following abdominal hysterectomy. A case of synergistic bacterial gangrene occurring after abdominal hysterectomy in a 43-year-old patient is presented. After multiple debridement procedures and porcine grafts, the patient responded satisfactorily and eventually recovered."}
{"id": "PMID:187993", "title": "Rare tumors of the orbit during childhood. Multiform glioblastoma, melanoma, cystic lymphangioma, hemangioendothelioma: 67ga scanning and anatomico-pathological aspects.", "content": "Four cases of orbital tumours observed in pediatric subjects aged 16 months, 2 1/2, 51/2, and 8 years are presented. Stress is laid on the rarity of these tumors: multiform glioblastoma, melanoma, cystic lymphangioma and hemangioendothelioma. The 67Ga citrate-scanning investigations and the anatomopathological findings are described in detail.", "contents": "Rare tumors of the orbit during childhood. Multiform glioblastoma, melanoma, cystic lymphangioma, hemangioendothelioma: 67ga scanning and anatomico-pathological aspects. Four cases of orbital tumours observed in pediatric subjects aged 16 months, 2 1/2, 51/2, and 8 years are presented. Stress is laid on the rarity of these tumors: multiform glioblastoma, melanoma, cystic lymphangioma and hemangioendothelioma. The 67Ga citrate-scanning investigations and the anatomopathological findings are described in detail."}
{"id": "PMID:187994", "title": "Objective signs of inferior alveolar nerve anesthesia in exodontia.", "content": "Objective determination of the adequacy of inferior alveolar nerve anesthesia is difficult. A dependable objective test based upon clinical observation of hundreds of patients during extraction of mandibular teeth, is presented. Following routine inferior alveolar nerve block anesthesia, time is allowed for subjective signs of \"tingling\" of the lower lip. Fully aware that the patient may respond to pressure in the absence of pain, the tooth to be extracted is tested. Gradual pressure of increasing intensity is applied with extracting forceps for 3 seconds, then suddenly released, providing a sudden stimulus. If the patient immediately moves or \"jumps,\" this response indicates inadequate anesthesia. If the patient does not respond to the sudden release of pressure, that tooth can be removed painlessly even though the patient may still respond to pressure.", "contents": "Objective signs of inferior alveolar nerve anesthesia in exodontia. Objective determination of the adequacy of inferior alveolar nerve anesthesia is difficult. A dependable objective test based upon clinical observation of hundreds of patients during extraction of mandibular teeth, is presented. Following routine inferior alveolar nerve block anesthesia, time is allowed for subjective signs of \"tingling\" of the lower lip. Fully aware that the patient may respond to pressure in the absence of pain, the tooth to be extracted is tested. Gradual pressure of increasing intensity is applied with extracting forceps for 3 seconds, then suddenly released, providing a sudden stimulus. If the patient immediately moves or \"jumps,\" this response indicates inadequate anesthesia. If the patient does not respond to the sudden release of pressure, that tooth can be removed painlessly even though the patient may still respond to pressure."}
{"id": "PMID:187995", "title": "[Guidelines for the treatment of facial-nerve injuries].", "content": "The electroneuronographic registration of the summating potentials of the face muscles has been used to assess the prognosis in 72 traumatic facial nerve lesions. The following guide-lines have evolved from the experience gained: (1) a conservative attitude is indicated if the degeneration of the motor fibus is less than 90% 6 days following onset of the palsy and (2) a surgical revision of the facial nerve is indicated if the degeneration of the motor fibres reaches more than 90% during the first 6 days following onset of the palsy. The clinical differentiation in early and delayed traumatic facial palsy cannot be used as a prognostic sign. The amount and rapidity of degeneration of the motor fibres has more prognostic value than the latency between trauma and onset of the palsy. The importance of electroneuronography for the prognosis of iatrogenic facial nerve lesions as well as the value of a careful follow-up of regeneration in facial nerve lesions with preserved continuity of the nerve are discussed.", "contents": "[Guidelines for the treatment of facial-nerve injuries]. The electroneuronographic registration of the summating potentials of the face muscles has been used to assess the prognosis in 72 traumatic facial nerve lesions. The following guide-lines have evolved from the experience gained: (1) a conservative attitude is indicated if the degeneration of the motor fibus is less than 90% 6 days following onset of the palsy and (2) a surgical revision of the facial nerve is indicated if the degeneration of the motor fibres reaches more than 90% during the first 6 days following onset of the palsy. The clinical differentiation in early and delayed traumatic facial palsy cannot be used as a prognostic sign. The amount and rapidity of degeneration of the motor fibres has more prognostic value than the latency between trauma and onset of the palsy. The importance of electroneuronography for the prognosis of iatrogenic facial nerve lesions as well as the value of a careful follow-up of regeneration in facial nerve lesions with preserved continuity of the nerve are discussed."}
{"id": "PMID:187997", "title": "Corticosterone in serum of adrenalectomized male rats.", "content": "Following total adrenalectomy of adult male rats, the corticosterone level in the sera declines in the first and second postoperative day from 4.79+/-1.66 mug to 0.56+/-0.24 per 100 ml. On the third postoperative day the value increases to 1.7+/-0.67 mug/100 ml and attains again control level on the 14th p.o. day (5.4+/-3.3 mug/100 ml). Stress, but not 10 i.u. of ACTH causes a further increase of the corticosterone content in the serum reaching 14.3+/-3.5 mug/100 ml, this value representing a much lower amount of hormone in comparison to stressed control animals (36.35+/-2.4 mug/ml). In adrenalectomized and castrated animals no corticosterone could be detected 14 days p.o.; nor do stress or ACTH cause any change.", "contents": "Corticosterone in serum of adrenalectomized male rats. Following total adrenalectomy of adult male rats, the corticosterone level in the sera declines in the first and second postoperative day from 4.79+/-1.66 mug to 0.56+/-0.24 per 100 ml. On the third postoperative day the value increases to 1.7+/-0.67 mug/100 ml and attains again control level on the 14th p.o. day (5.4+/-3.3 mug/100 ml). Stress, but not 10 i.u. of ACTH causes a further increase of the corticosterone content in the serum reaching 14.3+/-3.5 mug/100 ml, this value representing a much lower amount of hormone in comparison to stressed control animals (36.35+/-2.4 mug/ml). In adrenalectomized and castrated animals no corticosterone could be detected 14 days p.o.; nor do stress or ACTH cause any change."}
{"id": "PMID:188001", "title": "Lobular carcinoma of the breast in situ and infiltrating.", "content": "Lobular carcinoma in situ, while histologically delineated almost 35 years ago, is still being diagnosed and reported with differing qualitative and quantitative criteria. It is important to recognize this lesion because of its frequent bilaterality and risk of developing infiltrating carcinoma in the affected breast. Because of the apparent morphologic identity of the cell of ALH and the cell of LCIS, because both are associated with some increased risk of developing carcinoma, and because both have an increased propensity to be found simultaneously with carcinoma--especially lobular carcinoma--we believe these lesions should be looked upon as basically identical. Beginning with Ewing's astute intuition nearly 60 years ago18 and culminating with the 1967 report of McDivitt and others,50 pathologists and surgeons have gradually become aware of the long-term risk associated with this nonobligatorily, premalignant lesion (LCIS). As further studies have become available, it is clear that a large majority of women with lobular carcinoma in situ or atypical lobular hyperplasia retaining the involved breast will not develop infiltrating carcinoma. However, there is an increased risk of roughly 1 percent per year. Because of the increased risk, we believe that a meticulous long-term followup is mandatory, and suggest a physical examination every two to three months for the first few years supplemented with yearly mammography (as is now being done at Memorial Hospital for patients with atypical breast lesions6). With such a followup, we believe the mortality should fall well below 5 percent in a 20-year followup, and believe this is a risk that may be acceptable to the patient and her surgeon. The boundaries of the morphologic changes acceptable as ILC have been difficult for many pathologists (including ourselves) to delineate. This is borne out by widely varying incidence figures and is due, at least in part, to the frequent admixture of ILC with poorly differentiated duct carcinoma as well as problems in deciding how large and pleomorphic the cell nuclei may be, and still be designated as lobular in origin. We believe that about 4 to 6 percent of all breast carcinomas are infiltrating lobular, and incidence rates widely divergent from this should be scrutinized carefully. Prognostically, ILC behaves similarly to poorly differentiated duct carcinomas except for some increased risk of subsequent contralateral carcinoma. Future study of lobular disease should be directed toward its histogenesis, long-term risk, and the relative success of different treatment modalities. Hormonal studies and cell culture with chromosomal analysis might shed some light on the mechanism of what may be postmenopausal regression of LCIS.", "contents": "Lobular carcinoma of the breast in situ and infiltrating. Lobular carcinoma in situ, while histologically delineated almost 35 years ago, is still being diagnosed and reported with differing qualitative and quantitative criteria. It is important to recognize this lesion because of its frequent bilaterality and risk of developing infiltrating carcinoma in the affected breast. Because of the apparent morphologic identity of the cell of ALH and the cell of LCIS, because both are associated with some increased risk of developing carcinoma, and because both have an increased propensity to be found simultaneously with carcinoma--especially lobular carcinoma--we believe these lesions should be looked upon as basically identical. Beginning with Ewing's astute intuition nearly 60 years ago18 and culminating with the 1967 report of McDivitt and others,50 pathologists and surgeons have gradually become aware of the long-term risk associated with this nonobligatorily, premalignant lesion (LCIS). As further studies have become available, it is clear that a large majority of women with lobular carcinoma in situ or atypical lobular hyperplasia retaining the involved breast will not develop infiltrating carcinoma. However, there is an increased risk of roughly 1 percent per year. Because of the increased risk, we believe that a meticulous long-term followup is mandatory, and suggest a physical examination every two to three months for the first few years supplemented with yearly mammography (as is now being done at Memorial Hospital for patients with atypical breast lesions6). With such a followup, we believe the mortality should fall well below 5 percent in a 20-year followup, and believe this is a risk that may be acceptable to the patient and her surgeon. The boundaries of the morphologic changes acceptable as ILC have been difficult for many pathologists (including ourselves) to delineate. This is borne out by widely varying incidence figures and is due, at least in part, to the frequent admixture of ILC with poorly differentiated duct carcinoma as well as problems in deciding how large and pleomorphic the cell nuclei may be, and still be designated as lobular in origin. We believe that about 4 to 6 percent of all breast carcinomas are infiltrating lobular, and incidence rates widely divergent from this should be scrutinized carefully. Prognostically, ILC behaves similarly to poorly differentiated duct carcinomas except for some increased risk of subsequent contralateral carcinoma. Future study of lobular disease should be directed toward its histogenesis, long-term risk, and the relative success of different treatment modalities. Hormonal studies and cell culture with chromosomal analysis might shed some light on the mechanism of what may be postmenopausal regression of LCIS."}
{"id": "PMID:188006", "title": "Light microscopy of selected viral diseases (morphology of viral inclusion bodies).", "content": "A significant number of viruses produce intracellular changes, inclusion bodies, which do have specific and consistent features important to their identification. The inclusions must fulfill the designated criteria for the specific virus or a member of that group. The specific features of viral inclusions are consistent fixative-dependent artifacts: uniformity and familiarity of staining quality are important to the consistency of recognition and identification. Bouin's or Zenker's-acetic acid are the fixatives of choice, and a well-done hematoxylin and eosin stain offers the greatest uniformity of quality. Viral inclusions are not static objects in a cell and recognition of the range of development is often more important than the appearance of a single inclusion. Generally, most viruses within a group cause identical intracellular reactions and produce similar inclusion bodies, thus permitting the pathologist an accurate prediction of the etiologic agent in clinically undiagnosed or unsuspected viral disease. By correlating viral inclusion identification, clinical history, and physical findings the anatomic pathologist can make the diagnosis of many viral diseases rapidly, inexpensively, and with a high degree of accuracy when compared to the complex, expensive, and time consuming procedures of animal inoculation, tissue culture, or serology.", "contents": "Light microscopy of selected viral diseases (morphology of viral inclusion bodies). A significant number of viruses produce intracellular changes, inclusion bodies, which do have specific and consistent features important to their identification. The inclusions must fulfill the designated criteria for the specific virus or a member of that group. The specific features of viral inclusions are consistent fixative-dependent artifacts: uniformity and familiarity of staining quality are important to the consistency of recognition and identification. Bouin's or Zenker's-acetic acid are the fixatives of choice, and a well-done hematoxylin and eosin stain offers the greatest uniformity of quality. Viral inclusions are not static objects in a cell and recognition of the range of development is often more important than the appearance of a single inclusion. Generally, most viruses within a group cause identical intracellular reactions and produce similar inclusion bodies, thus permitting the pathologist an accurate prediction of the etiologic agent in clinically undiagnosed or unsuspected viral disease. By correlating viral inclusion identification, clinical history, and physical findings the anatomic pathologist can make the diagnosis of many viral diseases rapidly, inexpensively, and with a high degree of accuracy when compared to the complex, expensive, and time consuming procedures of animal inoculation, tissue culture, or serology."}
{"id": "PMID:188007", "title": "The mechanism of urinary concentration in nephrogenic diabetes insipidus.", "content": "The authors have evaluated urinary adenosine 3',5'-monophosphate (cyclic AMP) excretion and renal function during Pitressin administration, hypertonic saline administration, and water deprivation in two siblings with vasopressin-resistant diabetes insipidus and in normal control subjects. After vasopressin administration normal subjects experienced a 2-fold rise in urinary cyclic AMP excretion from 3.2 +/- 0.7 to 5.6 +/- 1.3 nmol/min (P less than 0.001) whereas cyclic AMP excretion was unchanged in both patients (patient AC 4.4 +/- 0.9 to 4.3 +/- 2.1; patient TC 2.2 +/- 0.9 to 2.6 +/- 0.9 nmol/min) with nephrogenic diabetes insipidus (NDI). Urinary cyclic AMP excretion was measured during infusion of 2.5% saline, after vasopressim administration, and after water deprivation. Cyclic AMP excretion was not different from control values in the NDI patients during any of the experimental conditions. Furthermore, there was no difference in cyclic AMP excretion when periods of dilute urine excretion (patient AC 4.5 +/- 1.1; patient TC 2.1 +/- 0.8 nmol/min) were compared with periods when urine concentration was greater than that of plasma (AC 3.5 +/- 1.3; TC 1.8 +/- 0.9 nmol/min). Both subjects responded to parathyroid hormone infusion with a 2-fold increase in urinary cyclic AMP excretion. Excretion of concentrated urine was paralleled by a marked decrease in urine flow to less than 1 ml/min/m2. During periods of hypotonic urine excretion (Uosm/Posm less than 1.0) average glomerular filtration rate (GFR) in patient AC was 67.0 +/- 3.0 ml/minm2 whereas in patient TC it was 70.1 +/- 8.1 ml/min/m2. When each patient was excreting a hypertonic urine (Uosm/Posm greater than 1.0) after fluid deprivation their GFR had decreased significantly (P = 0.001) to 31.6 +/- 8.9 and 33.3 +/- 10.3 ml/min/m2, respectively. Ability of these two subjects with NDI to concentrate their urine to Uosm/Posm greater than 1.0 in the absence of an increase in urinary cyclic AMP but associated with a decrease in GFR to 50% normal indicates that urinary concentration was effected by a reduction in GFR rather than a partial response to antidiuretic hormone (ADH). Their ability to concentrate their urine during periods of modest volume depletion would protect them from progressing to more severe stages of dehydration and result in the relatively benign course of their disease. It is feasible that in patients previously reported to have had clinically \"partial\" NDI this mechanism may have been operative.", "contents": "The mechanism of urinary concentration in nephrogenic diabetes insipidus. The authors have evaluated urinary adenosine 3',5'-monophosphate (cyclic AMP) excretion and renal function during Pitressin administration, hypertonic saline administration, and water deprivation in two siblings with vasopressin-resistant diabetes insipidus and in normal control subjects. After vasopressin administration normal subjects experienced a 2-fold rise in urinary cyclic AMP excretion from 3.2 +/- 0.7 to 5.6 +/- 1.3 nmol/min (P less than 0.001) whereas cyclic AMP excretion was unchanged in both patients (patient AC 4.4 +/- 0.9 to 4.3 +/- 2.1; patient TC 2.2 +/- 0.9 to 2.6 +/- 0.9 nmol/min) with nephrogenic diabetes insipidus (NDI). Urinary cyclic AMP excretion was measured during infusion of 2.5% saline, after vasopressim administration, and after water deprivation. Cyclic AMP excretion was not different from control values in the NDI patients during any of the experimental conditions. Furthermore, there was no difference in cyclic AMP excretion when periods of dilute urine excretion (patient AC 4.5 +/- 1.1; patient TC 2.1 +/- 0.8 nmol/min) were compared with periods when urine concentration was greater than that of plasma (AC 3.5 +/- 1.3; TC 1.8 +/- 0.9 nmol/min). Both subjects responded to parathyroid hormone infusion with a 2-fold increase in urinary cyclic AMP excretion. Excretion of concentrated urine was paralleled by a marked decrease in urine flow to less than 1 ml/min/m2. During periods of hypotonic urine excretion (Uosm/Posm less than 1.0) average glomerular filtration rate (GFR) in patient AC was 67.0 +/- 3.0 ml/minm2 whereas in patient TC it was 70.1 +/- 8.1 ml/min/m2. When each patient was excreting a hypertonic urine (Uosm/Posm greater than 1.0) after fluid deprivation their GFR had decreased significantly (P = 0.001) to 31.6 +/- 8.9 and 33.3 +/- 10.3 ml/min/m2, respectively. Ability of these two subjects with NDI to concentrate their urine to Uosm/Posm greater than 1.0 in the absence of an increase in urinary cyclic AMP but associated with a decrease in GFR to 50% normal indicates that urinary concentration was effected by a reduction in GFR rather than a partial response to antidiuretic hormone (ADH). Their ability to concentrate their urine during periods of modest volume depletion would protect them from progressing to more severe stages of dehydration and result in the relatively benign course of their disease. It is feasible that in patients previously reported to have had clinically \"partial\" NDI this mechanism may have been operative."}
{"id": "PMID:188010", "title": "The renin-angiotensin system and sodium excretion during gestation.", "content": "The renin-angiotensin system shows a marked increase in activity in normal pregnancy, with the major changes occurring in the first trimester. Evidence is presented to show that there is a physiologically inactive prorenin present in the plasma during pregnancy that achieves highest levels in the first half  of pregnancy. The significance of this \"acid-activated\" renin has yet to be determined. Plasma angiotensin II levels are elevated throughout normal pregnancy, and a significant positive relationship has been established between maternal venous and cord venous levels at delivery. Recent studies on plasma AII levels in pregnancy hypertension have shown a positive correlation between diastolic blood pressure and plasma AII, and there is evidence that the high circulating levels of angiotensin may result in a feed-back suppression of renal renin release. Studies on the fetal circulation at delivery have also shown high levels of AII in the cord venous blood of infants born to mothers with pregnancy hypertension. Despite the increased level of activity of the renin-angiotensin system in normal pregnancy, sodium homeostasis is maintained. The possible reasons for the increased activity are discussed briefly.", "contents": "The renin-angiotensin system and sodium excretion during gestation. The renin-angiotensin system shows a marked increase in activity in normal pregnancy, with the major changes occurring in the first trimester. Evidence is presented to show that there is a physiologically inactive prorenin present in the plasma during pregnancy that achieves highest levels in the first half  of pregnancy. The significance of this \"acid-activated\" renin has yet to be determined. Plasma angiotensin II levels are elevated throughout normal pregnancy, and a significant positive relationship has been established between maternal venous and cord venous levels at delivery. Recent studies on plasma AII levels in pregnancy hypertension have shown a positive correlation between diastolic blood pressure and plasma AII, and there is evidence that the high circulating levels of angiotensin may result in a feed-back suppression of renal renin release. Studies on the fetal circulation at delivery have also shown high levels of AII in the cord venous blood of infants born to mothers with pregnancy hypertension. Despite the increased level of activity of the renin-angiotensin system in normal pregnancy, sodium homeostasis is maintained. The possible reasons for the increased activity are discussed briefly."}
{"id": "PMID:188011", "title": "Control of ACh sensitivity in temporarily unconnected (\"decentralized\") segments of diaphragm-muscle fibres of the rat.", "content": "1. After a local lesion of the diaphragm muscle, which produced a segment of innervated muscle fibres connected with an intact nerve-free segment by a region of crushed muscle fibres, the sensitivity to ACh, the presence of tetrodotoxin resistant action potentials (AP) and the transmission of AP along the muscle fibres were studied. 2. Three days after local injury of the diaphragm muscle ACh sensitivity and TTX resistance appeared in the crushed and nerve-free segments between the place of injury and the tendineous attachment. 5-7 days after injury transmission of action potentials through the damaged to the undamaged (\"decentralized\"), nerve-free part of the fibres is restored. High ACh sensitivity and TTX resistance of the latter segment, however, are completely lost only 20 days after the local injury. During this period contractility of the muscle remains practically unchanged. Enzymatic activities (SDH, ATPase and phosphorylase) of the damaged part were lost 3 days after crushing and recovered slowly between 7-10 days of regeneration of the diaphragm muscle fibres. 3. The experiments suggest that during regeneration of damaged muscle fibres supersensitivity to ACh remains high inspite of normal AP activity and that intracellular mechanisms may be involved in the induction and disappearance of ACh hypersensitivity.", "contents": "Control of ACh sensitivity in temporarily unconnected (\"decentralized\") segments of diaphragm-muscle fibres of the rat. 1. After a local lesion of the diaphragm muscle, which produced a segment of innervated muscle fibres connected with an intact nerve-free segment by a region of crushed muscle fibres, the sensitivity to ACh, the presence of tetrodotoxin resistant action potentials (AP) and the transmission of AP along the muscle fibres were studied. 2. Three days after local injury of the diaphragm muscle ACh sensitivity and TTX resistance appeared in the crushed and nerve-free segments between the place of injury and the tendineous attachment. 5-7 days after injury transmission of action potentials through the damaged to the undamaged (\"decentralized\"), nerve-free part of the fibres is restored. High ACh sensitivity and TTX resistance of the latter segment, however, are completely lost only 20 days after the local injury. During this period contractility of the muscle remains practically unchanged. Enzymatic activities (SDH, ATPase and phosphorylase) of the damaged part were lost 3 days after crushing and recovered slowly between 7-10 days of regeneration of the diaphragm muscle fibres. 3. The experiments suggest that during regeneration of damaged muscle fibres supersensitivity to ACh remains high inspite of normal AP activity and that intracellular mechanisms may be involved in the induction and disappearance of ACh hypersensitivity."}
{"id": "PMID:188014", "title": "A deoxyadenylate kinase activity associated with polynucleotide phosphorylase from Micrococcus luteus.", "content": "We report here the presence of two enzymatic activities associated with highly purified preparations of polynucleotide phosphorylase from Micrococcus luteus. The first, a nuclease activity, which is not separated from the phosphorylase on hydroxylapatite, may be due to substitution of H2O for phosphate in the phosphorolysis reaction. The second activity, a deoxyadenylate kinase, the bulk of which is not resolved from the phosphorylase using gel filtration, sucrose density gradient centrifugation, DEAE-Sephadex, or hydroxylapatite chromatography, may represent a new activity of polynucleotide phosphorylase or be due to an enzyme which is tightly bound to the phosphorylase. Several properties of the kinase are described and its possible significance with respect to the overall enzyme mechanism is discussed.", "contents": "A deoxyadenylate kinase activity associated with polynucleotide phosphorylase from Micrococcus luteus. We report here the presence of two enzymatic activities associated with highly purified preparations of polynucleotide phosphorylase from Micrococcus luteus. The first, a nuclease activity, which is not separated from the phosphorylase on hydroxylapatite, may be due to substitution of H2O for phosphate in the phosphorolysis reaction. The second activity, a deoxyadenylate kinase, the bulk of which is not resolved from the phosphorylase using gel filtration, sucrose density gradient centrifugation, DEAE-Sephadex, or hydroxylapatite chromatography, may represent a new activity of polynucleotide phosphorylase or be due to an enzyme which is tightly bound to the phosphorylase. Several properties of the kinase are described and its possible significance with respect to the overall enzyme mechanism is discussed."}
{"id": "PMID:188015", "title": "Evolutionary trends in 18S ribosomal RNA nucleotide sequences of rat, mouse, hamster and man.", "content": "The large T1 ribonuclease fragments of 18S ribosomal RNA from four mammalian species, rat, mouse, hamster and man, were compared by two-dimensional homochromatography fingerprinting. The nucleotide sequences of the large T1 ribonuclease fragments, polypyrimidines and polypurines which were different among the four mammalian species were determined and compared. The method used for determining nucleotide sequences utilizes 32p-labeling of oligonucleotides at their 5'-termini by polynucleotide kinase, partial digestion by ribonucleases and analysis of labeled spots by homochromatography-fingerprinting. Several examples of point mutations were detected. It was of interest that the 18S rRNA of Chinese hamster has more oligonucleotide sequences in common with those of man that rat or mouse.", "contents": "Evolutionary trends in 18S ribosomal RNA nucleotide sequences of rat, mouse, hamster and man. The large T1 ribonuclease fragments of 18S ribosomal RNA from four mammalian species, rat, mouse, hamster and man, were compared by two-dimensional homochromatography fingerprinting. The nucleotide sequences of the large T1 ribonuclease fragments, polypyrimidines and polypurines which were different among the four mammalian species were determined and compared. The method used for determining nucleotide sequences utilizes 32p-labeling of oligonucleotides at their 5'-termini by polynucleotide kinase, partial digestion by ribonucleases and analysis of labeled spots by homochromatography-fingerprinting. Several examples of point mutations were detected. It was of interest that the 18S rRNA of Chinese hamster has more oligonucleotide sequences in common with those of man that rat or mouse."}
{"id": "PMID:188016", "title": "Partial characterization of an endonuclease activity which appears in nuclease free T4 polynucleotide kinase.", "content": "A nuclease activity has been found to appear in preparations of T4 induced polynucleotide kinase which had originally been nuclease free. The nuclease introduced random nicks into T7 DNA suggesting that it was an endonuclease. Destabilization of the kinase molecule by osmotic shock or by the removal of reducing agents, ATP or salts was shown to stimulate the endonuclease appearance. The molecular weight was found to be 32,000 +/- 10% by gel filtration on G100 Sephadex. The nuclease was active over a wide pH range from pH 5.0 to pH 9.2 in a number of buffer systems and required MgCl2 and reducing agent for maximum activity. Sodium azide did not affect the nuclease appearance.", "contents": "Partial characterization of an endonuclease activity which appears in nuclease free T4 polynucleotide kinase. A nuclease activity has been found to appear in preparations of T4 induced polynucleotide kinase which had originally been nuclease free. The nuclease introduced random nicks into T7 DNA suggesting that it was an endonuclease. Destabilization of the kinase molecule by osmotic shock or by the removal of reducing agents, ATP or salts was shown to stimulate the endonuclease appearance. The molecular weight was found to be 32,000 +/- 10% by gel filtration on G100 Sephadex. The nuclease was active over a wide pH range from pH 5.0 to pH 9.2 in a number of buffer systems and required MgCl2 and reducing agent for maximum activity. Sodium azide did not affect the nuclease appearance."}
{"id": "PMID:188017", "title": "A model for replication of the ends of linear chromosomes.", "content": "Linear chromosomes possessing internal repeats of their terminal sequences can form intramolecular crossed-strand exchanges that allow replication of the chromosome ends. Evidence is discussed that such a mechanism may be utilized during replication of herpes simplex virus DNA and during replication of macronuclear DNA from the hypotrichous ciliate Oxytricha.", "contents": "A model for replication of the ends of linear chromosomes. Linear chromosomes possessing internal repeats of their terminal sequences can form intramolecular crossed-strand exchanges that allow replication of the chromosome ends. Evidence is discussed that such a mechanism may be utilized during replication of herpes simplex virus DNA and during replication of macronuclear DNA from the hypotrichous ciliate Oxytricha."}
{"id": "PMID:188018", "title": "Stability of nucleosomes in native and reconstituted chromatins.", "content": "The stability of nucleosomes of SV40 minichromosomes extracted from infected cells or reconstituted by association of SV40 DNA and the four histones H2A, H2B, H3 and H4 was studied as a function of the ionic strength. As a measure of the stability of the nucleosome, we followed the disappearance of the nucleosomes from the original chromatin and their appearance on a \"competing\" DNA. We show here that the DNA and the histone components of the nucleosomes do not apprecially dissociate below 800 mM NaCl. At 800 mM and above, the histone moiety of the nucleosomes can dissociate from the DNA and efficiently participate to the formation of nucleosomes on a \"competing\" DNA.", "contents": "Stability of nucleosomes in native and reconstituted chromatins. The stability of nucleosomes of SV40 minichromosomes extracted from infected cells or reconstituted by association of SV40 DNA and the four histones H2A, H2B, H3 and H4 was studied as a function of the ionic strength. As a measure of the stability of the nucleosome, we followed the disappearance of the nucleosomes from the original chromatin and their appearance on a \"competing\" DNA. We show here that the DNA and the histone components of the nucleosomes do not apprecially dissociate below 800 mM NaCl. At 800 mM and above, the histone moiety of the nucleosomes can dissociate from the DNA and efficiently participate to the formation of nucleosomes on a \"competing\" DNA."}
{"id": "PMID:188019", "title": "Excision in vitro of the DNA bound carcinogen, 4-nitroquinoline 1-oxide.", "content": "It has been shown that 4-hydroxyaminoquinoline 1-oxide, the proximate form of the carcinogen 4-nitroquinoline 1-oxide, binds covalently to the purine bases of DNA. Here we report that carcinogen-bound nucleotides can be excised from DNA by a 5' leads to 3' exonuclease associated with DNA polymerase I of E. coli in the forms of either mononucleotides or oligonucleotides. Beef spleen phosphodiesterase II (5' leads to 3') also split carcinogen-bound nucleotides, while a 3' leads to 5' exonuclease of DNA polymerase I and E. coli exonuclease III (3' leads to 5') could not excise the modified nucleotide.", "contents": "Excision in vitro of the DNA bound carcinogen, 4-nitroquinoline 1-oxide. It has been shown that 4-hydroxyaminoquinoline 1-oxide, the proximate form of the carcinogen 4-nitroquinoline 1-oxide, binds covalently to the purine bases of DNA. Here we report that carcinogen-bound nucleotides can be excised from DNA by a 5' leads to 3' exonuclease associated with DNA polymerase I of E. coli in the forms of either mononucleotides or oligonucleotides. Beef spleen phosphodiesterase II (5' leads to 3') also split carcinogen-bound nucleotides, while a 3' leads to 5' exonuclease of DNA polymerase I and E. coli exonuclease III (3' leads to 5') could not excise the modified nucleotide."}
{"id": "PMID:188020", "title": "Variation in DNA swivel enzyme activity during the mammalian cell cycle.", "content": "Synchronized cells of a normal human lymphocytic cell line contain little swiven enzyme activity in G0 and G1 and high activity in Sphase. The level of activity in different growth phase appears to be related to the fraction of the population engaged in DNA replication. No endogenous inhibitor or activator of swiven activity could be demonstrated. The evidence implies that the enzyme may be present only during S phase; it is therefore a possible control factor for replication.", "contents": "Variation in DNA swivel enzyme activity during the mammalian cell cycle. Synchronized cells of a normal human lymphocytic cell line contain little swiven enzyme activity in G0 and G1 and high activity in Sphase. The level of activity in different growth phase appears to be related to the fraction of the population engaged in DNA replication. No endogenous inhibitor or activator of swiven activity could be demonstrated. The evidence implies that the enzyme may be present only during S phase; it is therefore a possible control factor for replication."}
{"id": "PMID:188021", "title": "Nucleotide sequence of the restriction fragments hind L and hind M of SV40 DNA.", "content": "The nucleotide sequence of the two minor SV40 DNA restriction fragments Hind L and Hind M is here reported. For this purpose we used 5'-32p-labeled DNA fragments either partially digested with snake venom diesterase for analysis by the wandering spot method or partially degraded with the base specific reagents dimethylsulphate or hydrazine for direct sequence analysis on gel. In the former procedure the strands were separated before degradation, while in the latter the strands were separated after modification but before the degradation. Due to the presence of several termination codons, the region Hind L - Hind M cannot be translated in a polypeptide. Also, no initiation codons for protein synthesis are present in this region.", "contents": "Nucleotide sequence of the restriction fragments hind L and hind M of SV40 DNA. The nucleotide sequence of the two minor SV40 DNA restriction fragments Hind L and Hind M is here reported. For this purpose we used 5'-32p-labeled DNA fragments either partially digested with snake venom diesterase for analysis by the wandering spot method or partially degraded with the base specific reagents dimethylsulphate or hydrazine for direct sequence analysis on gel. In the former procedure the strands were separated before degradation, while in the latter the strands were separated after modification but before the degradation. Due to the presence of several termination codons, the region Hind L - Hind M cannot be translated in a polypeptide. Also, no initiation codons for protein synthesis are present in this region."}
{"id": "PMID:188022", "title": "[Bone scintigraphy in renal osteopathy].", "content": "25 Patients with chronic renal disease are investigated. In 16 cases with conservative treatment the bone scintigram showed pathological uptake according to the creatinine level, mainly in the joints of iliosacrum, hip, knee and ankles. In three patients increased uptake in the skull was found. The bone uptake found by scintigraphy was highly pronounced in the patients treated by dialysis. The most frequently involved regions were the joints of iliosacrum and hip, facial cranium, skull, pelvis and metatarsus. The count-rate ratio of cranium to chest was significantly increased in 6 patients. The investigations 6 months later showed in 4 cases a further increase compared with the first values. Count-rates of the skull were found to be comparable to the highly increased uptake in Paget's disease. Bone scintigraphy is a suitable method to estimate semiquantitatively the bone turnover in renal disease.", "contents": "[Bone scintigraphy in renal osteopathy]. 25 Patients with chronic renal disease are investigated. In 16 cases with conservative treatment the bone scintigram showed pathological uptake according to the creatinine level, mainly in the joints of iliosacrum, hip, knee and ankles. In three patients increased uptake in the skull was found. The bone uptake found by scintigraphy was highly pronounced in the patients treated by dialysis. The most frequently involved regions were the joints of iliosacrum and hip, facial cranium, skull, pelvis and metatarsus. The count-rate ratio of cranium to chest was significantly increased in 6 patients. The investigations 6 months later showed in 4 cases a further increase compared with the first values. Count-rates of the skull were found to be comparable to the highly increased uptake in Paget's disease. Bone scintigraphy is a suitable method to estimate semiquantitatively the bone turnover in renal disease."}
{"id": "PMID:188023", "title": "Bone scintigraphy in children.", "content": "Bone scintigraphy with 99mTc-polyphosphate or 99mTc-pyrophosphate was carried out in 54 children suspected of bone disease. Signs of skeletal metastases were recognized in 13 children by scintigraphy whereas X-ray examination showed lesions in only 10 of these. In 5 children with primary osteosarcoma, three cases of fibrous dysplasia, and 4 cases of osteomyelitis, the lesions were clearly demonstrated by scintigraphy. Abnormal accumulation of radioactivity in soft tissue lesions was observed in primary adrenal neuroblastoma, Hodgkin's granuloma, and metastatic Burkitt's lymphoma. Several cases are reported, and the value of bone scintigraphy in children is discussed.", "contents": "Bone scintigraphy in children. Bone scintigraphy with 99mTc-polyphosphate or 99mTc-pyrophosphate was carried out in 54 children suspected of bone disease. Signs of skeletal metastases were recognized in 13 children by scintigraphy whereas X-ray examination showed lesions in only 10 of these. In 5 children with primary osteosarcoma, three cases of fibrous dysplasia, and 4 cases of osteomyelitis, the lesions were clearly demonstrated by scintigraphy. Abnormal accumulation of radioactivity in soft tissue lesions was observed in primary adrenal neuroblastoma, Hodgkin's granuloma, and metastatic Burkitt's lymphoma. Several cases are reported, and the value of bone scintigraphy in children is discussed."}
{"id": "PMID:188025", "title": "[Pleuresies in chronic pancreatitis and in pancreatic pseudocysts. A study apropos of 20 cases].", "content": "The pleurisies rich in amylase of the chronic pancreatitis and of pancreatic pseudo-cysts, studied in 20 cases, are quite unfrequent (0.5% of pleurisies of all kinds in the medical milieu). A pseudo-cyst was found 12 times out of 20 and a chronic pancreatitis without pseudocyst was found 8 times out of 20. Pleural effusion has a definite diagnostic valve, because in 70% of cases pancreatopathy cannot be recognized before it happens. The pleural liquid is rich in proteins and haemorrhagic in 2/3 of cases and its amylasic activity is either high or very high. Amylase level in pleural liquid is usually superior to amylasemia. The injection of lipiodol in the pleural cavity enables the visualization of a transdiaphragmatic fistula but this examination is not always well tolerated. The preoperatory cystography can opacify the pleura. In the absence of pseudo-cyst, medical treatment can dry the pleurisy in 70% of cases but does not modify the evolution of the pancreatic affection which will require surgery. Where a pseudo-cyst is concerned, surgery will often and quickly be the remedy.", "contents": "[Pleuresies in chronic pancreatitis and in pancreatic pseudocysts. A study apropos of 20 cases]. The pleurisies rich in amylase of the chronic pancreatitis and of pancreatic pseudo-cysts, studied in 20 cases, are quite unfrequent (0.5% of pleurisies of all kinds in the medical milieu). A pseudo-cyst was found 12 times out of 20 and a chronic pancreatitis without pseudocyst was found 8 times out of 20. Pleural effusion has a definite diagnostic valve, because in 70% of cases pancreatopathy cannot be recognized before it happens. The pleural liquid is rich in proteins and haemorrhagic in 2/3 of cases and its amylasic activity is either high or very high. Amylase level in pleural liquid is usually superior to amylasemia. The injection of lipiodol in the pleural cavity enables the visualization of a transdiaphragmatic fistula but this examination is not always well tolerated. The preoperatory cystography can opacify the pleura. In the absence of pseudo-cyst, medical treatment can dry the pleurisy in 70% of cases but does not modify the evolution of the pancreatic affection which will require surgery. Where a pseudo-cyst is concerned, surgery will often and quickly be the remedy."}
{"id": "PMID:188030", "title": "Formaldehyde treated gelatin as a gel exclusion agent.", "content": "A high molecular weight fraction of gelatin precipitated from a solution of Difco gelatin with polyethylene glycol has several favourable properties in gel exclusion chromatography. To manufacture the gel exclusion agent, the gelatin was dissolved in hot water, allowed to set in the cold and rendered insoluble by reaction with formaldehyde. When finely disrupted and used as bed material in columns this gel is capable of separating protein components from mixtures of proteins of widely different molecular weights. Favourable properties include elasticity at relatively low concentration, its availability and its inexpensive nature.", "contents": "Formaldehyde treated gelatin as a gel exclusion agent. A high molecular weight fraction of gelatin precipitated from a solution of Difco gelatin with polyethylene glycol has several favourable properties in gel exclusion chromatography. To manufacture the gel exclusion agent, the gelatin was dissolved in hot water, allowed to set in the cold and rendered insoluble by reaction with formaldehyde. When finely disrupted and used as bed material in columns this gel is capable of separating protein components from mixtures of proteins of widely different molecular weights. Favourable properties include elasticity at relatively low concentration, its availability and its inexpensive nature."}
{"id": "PMID:188032", "title": "A large product of cell-free translation of messenger RNA coding for corticotropin.", "content": "Polyadenylate-containing RNA prepared from the membrane fraction of bovine anterior pituitary gland was shown to direct the synthesis of a large translation product related to corticotropin (adrenocorticotropic hormone) in a cell-free system derived from wheat germ. This product was identified by immunoprecipitation with specific antibody against corticotropin, followed by electrophoretic analysis of the dissociated immunoprecipitate on sodium dodecyl sulfate-polyacrylamide gel. Further evidence for the identity of the translation product was provided by the presence of a common peptide in the chymotryptic digest of [35S]methionine-labeled cell-free product and in that of authentic corticotropin. The molecular weight of the translation product was estimated to be approximately 35,000, based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results indicate that corticotropin messenger RNA directs the cell-free synthesis of a product that contains the amino acid sequence of corticotropin but is much larger than this hormone.", "contents": "A large product of cell-free translation of messenger RNA coding for corticotropin. Polyadenylate-containing RNA prepared from the membrane fraction of bovine anterior pituitary gland was shown to direct the synthesis of a large translation product related to corticotropin (adrenocorticotropic hormone) in a cell-free system derived from wheat germ. This product was identified by immunoprecipitation with specific antibody against corticotropin, followed by electrophoretic analysis of the dissociated immunoprecipitate on sodium dodecyl sulfate-polyacrylamide gel. Further evidence for the identity of the translation product was provided by the presence of a common peptide in the chymotryptic digest of [35S]methionine-labeled cell-free product and in that of authentic corticotropin. The molecular weight of the translation product was estimated to be approximately 35,000, based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results indicate that corticotropin messenger RNA directs the cell-free synthesis of a product that contains the amino acid sequence of corticotropin but is much larger than this hormone."}
{"id": "PMID:188033", "title": "Adrenal cholesterol uptake from plasma lipoproteins: regulation by corticotropin.", "content": "The transfer of lipoprotein-bound cholesterol into adrenal cells was examined. Adrenal glands from unstimulated or corticotropin stimulated hypophysectomized rats were incubated with high density lipoprotein (HDL) or low density lipoprotein LDL containing radiolabeled cholesterol. The rate of transfer of labeled cholesterol from HDL into the glands was two to three times greater than from LDL. Corticotropin stimulation increased the transfer of cholesterol from HDL but not LDL. The effects of corticotropin were not dependent on subsequent cholesterol utilization for steroidogenesis. The process of cholesterol transfer from HDL was linear with time over 2 hr at 37 degrees and greatly reduced at 4 degrees. In addition, the transfer process became saturated above an HDL cholesterol concentration of 900 mug/ml. About 25% of the labeled adrenal cholesterol arising from HDL was recovered within the mitochondria. The labeled cholesterol within isolated mitochondria could undergo mitochondrial conversion to pregnenolone. Finally, the delipidated HDL apolipoproteins, apoA-I and apoA-II, when added to incubations containing less than saturating concentrations of HDL, stimulated transfer of labeled cholesterol from HDL to adrenal cells. These studies suggest that rat adrenal tissue possesses an HDL specific hormonally-responsive mechanism for accumulating extracellular cholesterol and that apoA-I and apoA-II have a significant function in the uptake process.", "contents": "Adrenal cholesterol uptake from plasma lipoproteins: regulation by corticotropin. The transfer of lipoprotein-bound cholesterol into adrenal cells was examined. Adrenal glands from unstimulated or corticotropin stimulated hypophysectomized rats were incubated with high density lipoprotein (HDL) or low density lipoprotein LDL containing radiolabeled cholesterol. The rate of transfer of labeled cholesterol from HDL into the glands was two to three times greater than from LDL. Corticotropin stimulation increased the transfer of cholesterol from HDL but not LDL. The effects of corticotropin were not dependent on subsequent cholesterol utilization for steroidogenesis. The process of cholesterol transfer from HDL was linear with time over 2 hr at 37 degrees and greatly reduced at 4 degrees. In addition, the transfer process became saturated above an HDL cholesterol concentration of 900 mug/ml. About 25% of the labeled adrenal cholesterol arising from HDL was recovered within the mitochondria. The labeled cholesterol within isolated mitochondria could undergo mitochondrial conversion to pregnenolone. Finally, the delipidated HDL apolipoproteins, apoA-I and apoA-II, when added to incubations containing less than saturating concentrations of HDL, stimulated transfer of labeled cholesterol from HDL to adrenal cells. These studies suggest that rat adrenal tissue possesses an HDL specific hormonally-responsive mechanism for accumulating extracellular cholesterol and that apoA-I and apoA-II have a significant function in the uptake process."}
{"id": "PMID:188034", "title": "Interaction of integral and peripheral membrane proteins: affinity labeling of yeast cytochrome oxidase by modified yeast cytochrome c.", "content": "To identify possible substrate-binding subunit(s) of yeast cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1-9-3-1), the purified enzyme was reacted with yeast iso-1-cytochrome c whose single free sulfhydryl group at position 107 had been activated with 5,5'-dithiobis(2-nitrobenzoate). The resulting cytochrome c derivative appeared to function as an \"affinity-label\" of cytochrome oxidase, since it rapidly inactivated the enzyme. Inactivation was competitively prevented by underivatized cytochrome c. When the \"affinity-labeled\" oxidase was analyzed by two-dimensional polyacrylamide electrophoresis in dodecyl sulfate (separation in the second dimension being carried out in the presence of excess sulfhydryl compound), it was found that the derivatized cytochrome c had specifically formed a mixed disulfide with the mitochondrially made subunit III (apparent molecular weight 24,000) of the oxidase. Similar results were obtained when underivatized iso-I-cytochrome c was crosslinked to the oxidase by oxidative disulfide bridge formation in the presence of ortho-phenanthroline and Cu++. These data indicate that the hydrophobic mitochondrially made subunit III of yeast cytochrome c oxidase is in close proximity to the cytochrome c binding site on the enzyme. Since cytochrome c and the mitochondrially made cytochrome oxidase subunit III are typical peripheral and integral membrane proteins, respectively, the present study suggests a useful approach for analyzing specific interactions between these different classes of membrane proteins.", "contents": "Interaction of integral and peripheral membrane proteins: affinity labeling of yeast cytochrome oxidase by modified yeast cytochrome c. To identify possible substrate-binding subunit(s) of yeast cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1-9-3-1), the purified enzyme was reacted with yeast iso-1-cytochrome c whose single free sulfhydryl group at position 107 had been activated with 5,5'-dithiobis(2-nitrobenzoate). The resulting cytochrome c derivative appeared to function as an \"affinity-label\" of cytochrome oxidase, since it rapidly inactivated the enzyme. Inactivation was competitively prevented by underivatized cytochrome c. When the \"affinity-labeled\" oxidase was analyzed by two-dimensional polyacrylamide electrophoresis in dodecyl sulfate (separation in the second dimension being carried out in the presence of excess sulfhydryl compound), it was found that the derivatized cytochrome c had specifically formed a mixed disulfide with the mitochondrially made subunit III (apparent molecular weight 24,000) of the oxidase. Similar results were obtained when underivatized iso-I-cytochrome c was crosslinked to the oxidase by oxidative disulfide bridge formation in the presence of ortho-phenanthroline and Cu++. These data indicate that the hydrophobic mitochondrially made subunit III of yeast cytochrome c oxidase is in close proximity to the cytochrome c binding site on the enzyme. Since cytochrome c and the mitochondrially made cytochrome oxidase subunit III are typical peripheral and integral membrane proteins, respectively, the present study suggests a useful approach for analyzing specific interactions between these different classes of membrane proteins."}
{"id": "PMID:188035", "title": "Alterations in cell surface glycosphingolipids and other lipid classes of fibroblasts in familial hypercholesterolemia.", "content": "The glycosphingolipids (GSL) and other major lipid classes were studied in cultured fibroblasts from a family with familial hypercholesterolemia. The GSL content in cells grown in medium containing fetal calf serum was increased 5-fold in the homozygote and 2- to 3-fold in both heterozygous parents. Cell surface labeling experiments, using the membrane probe galactose oxidase followed by reduction with KB3H4, showed an increased incorporation of 3H by the homozygous cells into GL4 (4-fold), GM3 (2- to 3-fold), and GL3a and GD3 (1- to 2-fold); the amount of 3H incorporated by the heterozygous cells was in between that of the homozygous and normal fibroblasts. The specific radioactivity of each of the GSL, except GL2a, was lower in the mutant cells. This unlabeled pool of GSL may be buried in the membrane matrix (less exposure), or located intracellularly, or both. The phospholipids were most markedly elevated (3-fold) in homozygous cells, with a disproportionate increase in phosphatidic acid and sphingomyelin (5- to 6-fold). The content of the GSL, except GL2a, and of the phospholipids was reduced about one-half in the homozygous fibroblasts grown in lipoprotein-deficient medium for 24 hr; by 5 days the GSL content was reduced to only 1.3 times normal and phospholipids to below normal. Incubation of normal fibroblasts in lipoprotein-dificient medium 24 hr had no effect on the GSL or phospholipid content; at 5 days, there was a 50% increase in both GL3a and GL4 with a 25% increase in GM3; there was no change in the phospholipid content. These data suggest that the defective regulation of lipid metabolism in this syndrome may be more extensive than previously realized.", "contents": "Alterations in cell surface glycosphingolipids and other lipid classes of fibroblasts in familial hypercholesterolemia. The glycosphingolipids (GSL) and other major lipid classes were studied in cultured fibroblasts from a family with familial hypercholesterolemia. The GSL content in cells grown in medium containing fetal calf serum was increased 5-fold in the homozygote and 2- to 3-fold in both heterozygous parents. Cell surface labeling experiments, using the membrane probe galactose oxidase followed by reduction with KB3H4, showed an increased incorporation of 3H by the homozygous cells into GL4 (4-fold), GM3 (2- to 3-fold), and GL3a and GD3 (1- to 2-fold); the amount of 3H incorporated by the heterozygous cells was in between that of the homozygous and normal fibroblasts. The specific radioactivity of each of the GSL, except GL2a, was lower in the mutant cells. This unlabeled pool of GSL may be buried in the membrane matrix (less exposure), or located intracellularly, or both. The phospholipids were most markedly elevated (3-fold) in homozygous cells, with a disproportionate increase in phosphatidic acid and sphingomyelin (5- to 6-fold). The content of the GSL, except GL2a, and of the phospholipids was reduced about one-half in the homozygous fibroblasts grown in lipoprotein-deficient medium for 24 hr; by 5 days the GSL content was reduced to only 1.3 times normal and phospholipids to below normal. Incubation of normal fibroblasts in lipoprotein-dificient medium 24 hr had no effect on the GSL or phospholipid content; at 5 days, there was a 50% increase in both GL3a and GL4 with a 25% increase in GM3; there was no change in the phospholipid content. These data suggest that the defective regulation of lipid metabolism in this syndrome may be more extensive than previously realized."}
{"id": "PMID:188036", "title": "Effect of 3':5'-cyclic AMP on glucose transport in rat adipocytes.", "content": "An indirect method for obtaining a reliable measure of the rate of glucose transport into adipocytes is described. Evidence is presented that altered levels of 3':5'-cyclic AMP can influence the transport of glucose into adipocytes. When cyclic AMP levels were lowered with antilipolytic agents (insulin, nicotinic acid, or clofibrate), rates of glucose transport were increased. In contrast, when adipose tissue levels of cyclic AMP were elevated by lipolytic hormones or theophylline, glucose transport when cyclic AMP levels were elevated by lipolytic agents. Agents that can raise cyclic AMP but inhibit lipolytic (procaine, amitryptyline, and phenylethylbiguanide) reduced the rate of glucose transport. Other data are presented that are consistent with the conclusion that cyclic AMP inhibits glucose transport into adipocytes.", "contents": "Effect of 3':5'-cyclic AMP on glucose transport in rat adipocytes. An indirect method for obtaining a reliable measure of the rate of glucose transport into adipocytes is described. Evidence is presented that altered levels of 3':5'-cyclic AMP can influence the transport of glucose into adipocytes. When cyclic AMP levels were lowered with antilipolytic agents (insulin, nicotinic acid, or clofibrate), rates of glucose transport were increased. In contrast, when adipose tissue levels of cyclic AMP were elevated by lipolytic hormones or theophylline, glucose transport when cyclic AMP levels were elevated by lipolytic agents. Agents that can raise cyclic AMP but inhibit lipolytic (procaine, amitryptyline, and phenylethylbiguanide) reduced the rate of glucose transport. Other data are presented that are consistent with the conclusion that cyclic AMP inhibits glucose transport into adipocytes."}
{"id": "PMID:188037", "title": "Subnuclear systems for synthesis of simian virus 40 DNA in vitro.", "content": "We have developed two subnuclear systems for synthesis of DNA of simian virus 40 in vitro. We prepare chromatin from infected cells by the method of Hancock [(1974) J. Mol. Biol. 86, 649-663]; these \"chromatin bodies\" can be disrupted and large debris can be pelleted, leaving a supernatant (\"soluble system\"). Both chromatin bodies and the soluble system incorporate deoxyribonucleoside triphosphates into nucleoprotein complexes that contain simian virus 40 DNA. The DNA labeled in short pulses sediments in neutral sucrose gradients slightly faster than mature simian virus 40 DNA, as expected for replicating intermediate. When rebanded in alkaline sucrose gradients, about half of the radioactivity is found in short strands (200-300 nucleotides) and half in longer strands (up to full viral size). When these systems are supplemented with a cytoplasmic preparation from HeLa cells, synthesis is stimulated about 5-fold, and the short strands are converted into strands of up to full viral length as well as into covalently closed circles. These subnuclear DNA-replicating systems should be useful for biochemical fractionation and characterization of some of the proteins required for DNA replication.", "contents": "Subnuclear systems for synthesis of simian virus 40 DNA in vitro. We have developed two subnuclear systems for synthesis of DNA of simian virus 40 in vitro. We prepare chromatin from infected cells by the method of Hancock [(1974) J. Mol. Biol. 86, 649-663]; these \"chromatin bodies\" can be disrupted and large debris can be pelleted, leaving a supernatant (\"soluble system\"). Both chromatin bodies and the soluble system incorporate deoxyribonucleoside triphosphates into nucleoprotein complexes that contain simian virus 40 DNA. The DNA labeled in short pulses sediments in neutral sucrose gradients slightly faster than mature simian virus 40 DNA, as expected for replicating intermediate. When rebanded in alkaline sucrose gradients, about half of the radioactivity is found in short strands (200-300 nucleotides) and half in longer strands (up to full viral size). When these systems are supplemented with a cytoplasmic preparation from HeLa cells, synthesis is stimulated about 5-fold, and the short strands are converted into strands of up to full viral length as well as into covalently closed circles. These subnuclear DNA-replicating systems should be useful for biochemical fractionation and characterization of some of the proteins required for DNA replication."}
{"id": "PMID:188038", "title": "Hydrolysis of nicotinamide adenine dinucleotide by choleragen and its A protomer: possible role in the activation of adenylate cyclase.", "content": "Choleragen and the isolated A protomer catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide. The protein with NADase activity (NAD nucleosidase; NAD glycohydrolase, EC 3-2-2-5) migrated on polyacrylamide gels with choleragen, and chromatographed on Bio-Gel P-60 columns with the A protomer. The NADase activity of choleragen and of the A protomer was increased markedly in acetate and phosphate buffers, and enhanced over 10-fold by dithiothreitol in high concentration. NAD hydrolysis was proportional to choleragen concentration; the Michaelis constant for NAD was about 4 mM with both choleragen and the A protomer. The demonstration that the A protomer of choleragen catalyzes an enzymatic reaction involving activation of the ribosyl-nicotinamide bond of NAD, a reaction analogols to those catalyzed by diphtheria toxin, supports the hypothesis that activation of adenylate cyclase by choleragen involves the ADP-ribosylation of an appropriate acceptor protein.", "contents": "Hydrolysis of nicotinamide adenine dinucleotide by choleragen and its A protomer: possible role in the activation of adenylate cyclase. Choleragen and the isolated A protomer catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide. The protein with NADase activity (NAD nucleosidase; NAD glycohydrolase, EC 3-2-2-5) migrated on polyacrylamide gels with choleragen, and chromatographed on Bio-Gel P-60 columns with the A protomer. The NADase activity of choleragen and of the A protomer was increased markedly in acetate and phosphate buffers, and enhanced over 10-fold by dithiothreitol in high concentration. NAD hydrolysis was proportional to choleragen concentration; the Michaelis constant for NAD was about 4 mM with both choleragen and the A protomer. The demonstration that the A protomer of choleragen catalyzes an enzymatic reaction involving activation of the ribosyl-nicotinamide bond of NAD, a reaction analogols to those catalyzed by diphtheria toxin, supports the hypothesis that activation of adenylate cyclase by choleragen involves the ADP-ribosylation of an appropriate acceptor protein."}
{"id": "PMID:188039", "title": "Distribution of 3':5'-cyclic AMP and 3':5'-cyclic GMP in rabbit retina in vivo: selective effects of dark and light adaptation and ischemia.", "content": "By use of highly sensitive radioimmunoassays, 3':5'-cyclic AMP (cAMP) and 3':5'-cyclic GMP (cGMP) were measured in individual layers of light- and dark-adapted rabbit retinas, and the effects of ischemia were determined. In light-adapted retinas, cGMP levels ranged 50-fold, with over 90% of the total concentrated in the photoreceptor cells. The layer of outer segments contained 95 mumol/kg of dry weight, or three times the concentration present in the remainder of the photoreceptor cell layers. By contrast, levels of cAMP varied only 4-fold; the lowest level (6 mumol/kg of dry weight) was found in the outer segment layer and the highest level (22 mumol/kg of dry weight) in the inner segment layer of the photoreceptor cells. Dark adaptation elevated cGMP levels only in retinal layers containing photoreceptor cells, and the greatest proportional increase was observed in the synaptic layer of photoreceptor cells. Dark adaptation also caused increases of cAMP that were restricted to the outer plexiform and outer nuclear layers. Ischemia lowered cGMP levels, but only in retinal layers containing photoreceptor cells, and elevated cAMP levels, primarily in the inner layers of the retina. The effects of ischemia were greater in the dark-adapted than in light-adapted retinas. These results indicate that cGMP and cAMP levels in retina are influenced by the light adaptational state, that ischemia markedly modifies these processes, and that the effects of both light exposure and ischemia are regionally selective.", "contents": "Distribution of 3':5'-cyclic AMP and 3':5'-cyclic GMP in rabbit retina in vivo: selective effects of dark and light adaptation and ischemia. By use of highly sensitive radioimmunoassays, 3':5'-cyclic AMP (cAMP) and 3':5'-cyclic GMP (cGMP) were measured in individual layers of light- and dark-adapted rabbit retinas, and the effects of ischemia were determined. In light-adapted retinas, cGMP levels ranged 50-fold, with over 90% of the total concentrated in the photoreceptor cells. The layer of outer segments contained 95 mumol/kg of dry weight, or three times the concentration present in the remainder of the photoreceptor cell layers. By contrast, levels of cAMP varied only 4-fold; the lowest level (6 mumol/kg of dry weight) was found in the outer segment layer and the highest level (22 mumol/kg of dry weight) in the inner segment layer of the photoreceptor cells. Dark adaptation elevated cGMP levels only in retinal layers containing photoreceptor cells, and the greatest proportional increase was observed in the synaptic layer of photoreceptor cells. Dark adaptation also caused increases of cAMP that were restricted to the outer plexiform and outer nuclear layers. Ischemia lowered cGMP levels, but only in retinal layers containing photoreceptor cells, and elevated cAMP levels, primarily in the inner layers of the retina. The effects of ischemia were greater in the dark-adapted than in light-adapted retinas. These results indicate that cGMP and cAMP levels in retina are influenced by the light adaptational state, that ischemia markedly modifies these processes, and that the effects of both light exposure and ischemia are regionally selective."}
{"id": "PMID:188040", "title": "Inhibition and stimulation of the development of the bioluminescent system in Beneckea harveyi by cyclic GMP.", "content": "The development of the luminescence system in Beneckea harveyi is controlled by cyclic nucleotides at the level of transcription. In the wild type, it is repressed by exogenously added guanosine 3':5'-cyclic monophosphate and this repression is overcome by the addition of adenosine 3':5'-cyclic monophosphate. These observations alone support a model in which these nucleotides act antagonistically. On the other hand, in a mutant requiring adenosine 3':5'-cyclic monophosphate for maximum luminescence, guanosine 3':5'-cyclic monophosphate stimulates the synthesis of the luminescence system at low concentrations and inhibits it at higher concentrations. These results are apparently not consistent with a model involving a simple antagonistic effect of guanosine 3':5'-cyclic monophosphate on the action of adenosine 3':5'-cyclic monophosphate.", "contents": "Inhibition and stimulation of the development of the bioluminescent system in Beneckea harveyi by cyclic GMP. The development of the luminescence system in Beneckea harveyi is controlled by cyclic nucleotides at the level of transcription. In the wild type, it is repressed by exogenously added guanosine 3':5'-cyclic monophosphate and this repression is overcome by the addition of adenosine 3':5'-cyclic monophosphate. These observations alone support a model in which these nucleotides act antagonistically. On the other hand, in a mutant requiring adenosine 3':5'-cyclic monophosphate for maximum luminescence, guanosine 3':5'-cyclic monophosphate stimulates the synthesis of the luminescence system at low concentrations and inhibits it at higher concentrations. These results are apparently not consistent with a model involving a simple antagonistic effect of guanosine 3':5'-cyclic monophosphate on the action of adenosine 3':5'-cyclic monophosphate."}
{"id": "PMID:188041", "title": "Determination of molecular weight of the protein moiety in protein-detergent complexes without direct knowledge of detergent binding.", "content": "Sedimentation equilibrium measurements can be used to determine the molecular weight of the protein moiety of a protein-detergent complex without prior knowledge of detergent binding. The procedure is to adjust the solvent density by addition of D2O so as to blank out the contribution of bound detergent to the sedimentation potential. An approximate measure of detergent binding can be obtained from the effect of solvent density on the sedimentation result. The procedure is also applicable to protein-lipid complexes. It can be used for complexes containing both lipid and detergent if the lipid content is known. The use of the method is demonstrated by experimental data for the AI polypeptide of serum high density lipoprotein, in separate complexes with nonionic detergents and with a phospholipid.", "contents": "Determination of molecular weight of the protein moiety in protein-detergent complexes without direct knowledge of detergent binding. Sedimentation equilibrium measurements can be used to determine the molecular weight of the protein moiety of a protein-detergent complex without prior knowledge of detergent binding. The procedure is to adjust the solvent density by addition of D2O so as to blank out the contribution of bound detergent to the sedimentation potential. An approximate measure of detergent binding can be obtained from the effect of solvent density on the sedimentation result. The procedure is also applicable to protein-lipid complexes. It can be used for complexes containing both lipid and detergent if the lipid content is known. The use of the method is demonstrated by experimental data for the AI polypeptide of serum high density lipoprotein, in separate complexes with nonionic detergents and with a phospholipid."}
{"id": "PMID:188042", "title": "Induction and decay of glucagon-induced amino acid transport in primary cultures of adult rat liver cells: paradoxical effects of cycloheximide and puromycin.", "content": "Liver parenchymal cells were isolated from adult rats and cultured in collagen-coated plastic petri dishes in serum-free medium. Glucagon induced 4- to 5-fold increases in alpha-aminoisobutyric acid (AIB) transport within 6 hr. Dexaemthasone had no direct effect on AIB transport but greatly potentiated the induction by glucagon (\"permissive effect\"). Levels of 3':5'-cyclic AMP increased 30- to 100-fold within 30 min after glucagon addition to cultures that had been treated with dexamethasone, and dibutyryl cyclic AMP mimicked the glucagon induction of AIB transport. Additionally, dexamethasone exerted a \"permissive\" effect on induction of AIB transport by dibutyryl cyclic AMP, whereas the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine induced AIB transport only in cultures that had been treated with dexamethasone. Induction of AIB transport was not dependent upon the continued presence of glucagon, but induced AIB transport activity decayed to uninduced levels within 3-4 hr after glucagon removal. The protein syntesis inhibitors puromycin and cycloheximide inhibited both induction and decay of glucagon induced AIB transport, but had a stabilizing effect if added once induction or decay had commenced. Unlike cycloheximide, the inhibitory effect of puromycin on the glucagon induction of AIB transport was reversible.", "contents": "Induction and decay of glucagon-induced amino acid transport in primary cultures of adult rat liver cells: paradoxical effects of cycloheximide and puromycin. Liver parenchymal cells were isolated from adult rats and cultured in collagen-coated plastic petri dishes in serum-free medium. Glucagon induced 4- to 5-fold increases in alpha-aminoisobutyric acid (AIB) transport within 6 hr. Dexaemthasone had no direct effect on AIB transport but greatly potentiated the induction by glucagon (\"permissive effect\"). Levels of 3':5'-cyclic AMP increased 30- to 100-fold within 30 min after glucagon addition to cultures that had been treated with dexamethasone, and dibutyryl cyclic AMP mimicked the glucagon induction of AIB transport. Additionally, dexamethasone exerted a \"permissive\" effect on induction of AIB transport by dibutyryl cyclic AMP, whereas the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine induced AIB transport only in cultures that had been treated with dexamethasone. Induction of AIB transport was not dependent upon the continued presence of glucagon, but induced AIB transport activity decayed to uninduced levels within 3-4 hr after glucagon removal. The protein syntesis inhibitors puromycin and cycloheximide inhibited both induction and decay of glucagon induced AIB transport, but had a stabilizing effect if added once induction or decay had commenced. Unlike cycloheximide, the inhibitory effect of puromycin on the glucagon induction of AIB transport was reversible."}
{"id": "PMID:188043", "title": "Conversion of 3T3 fibroblasts into adipose cells: triggering of differentiation by prostaglandin F2alpha and 1-methyl-3-isobutyl xanthine.", "content": "Green and Kehinde [(1974) cell 1, 113-116] have isolated clones of Swiss 3T3 fibriblasts that are able to convert to adipose cells. In this paper we report on two chemicals (prostaglandin F2alpha, 0.1 mug ml, and 1-methyl-3-isobutyl xanthine, 0.5 mM) that are able to rapidly and irreversibly program the fibroblasts to differentiate into adipose cells. Confluent cultures treated with prostaglandin F2alpha and insulin for 3-5 days, followed by insulin alone for 7-48 hr, yield numerous adipocyte colonies compared to control dishes and dishes treated with insulin alone. Cells treated with prostaglandin F2alpha or 1-methyl-3-isobutyl xanthine alone, rinsed, and then exposed to insulin gave similar results, indicating that the continuous presence of the triggering agent is not required to elicit the conversion of the fibroblasts to adipocytes. Agents that raise intracellular levels of 3':5'-cyclic AMP. 1.0 mM; 8-bromo-cyclic AMP,0.5 mM; and prostaglandin E1, 0.1 mug/ml) do not trigger the conversion process, suggesting that cyclic AMP may not be the mediator of differentiation in these cells. 8-Bromo-cyclic AMP, however, does induce thase; 3':5'-nucleotidohydrolase; EC 3.1.4.17) in these cells; the induction appears to be mediated by increases in intracellular cyclic AMP levels. These results indicate that this cell line might offer a system for studying the regulation of a type of cellular differentiation.", "contents": "Conversion of 3T3 fibroblasts into adipose cells: triggering of differentiation by prostaglandin F2alpha and 1-methyl-3-isobutyl xanthine. Green and Kehinde [(1974) cell 1, 113-116] have isolated clones of Swiss 3T3 fibriblasts that are able to convert to adipose cells. In this paper we report on two chemicals (prostaglandin F2alpha, 0.1 mug ml, and 1-methyl-3-isobutyl xanthine, 0.5 mM) that are able to rapidly and irreversibly program the fibroblasts to differentiate into adipose cells. Confluent cultures treated with prostaglandin F2alpha and insulin for 3-5 days, followed by insulin alone for 7-48 hr, yield numerous adipocyte colonies compared to control dishes and dishes treated with insulin alone. Cells treated with prostaglandin F2alpha or 1-methyl-3-isobutyl xanthine alone, rinsed, and then exposed to insulin gave similar results, indicating that the continuous presence of the triggering agent is not required to elicit the conversion of the fibroblasts to adipocytes. Agents that raise intracellular levels of 3':5'-cyclic AMP. 1.0 mM; 8-bromo-cyclic AMP,0.5 mM; and prostaglandin E1, 0.1 mug/ml) do not trigger the conversion process, suggesting that cyclic AMP may not be the mediator of differentiation in these cells. 8-Bromo-cyclic AMP, however, does induce thase; 3':5'-nucleotidohydrolase; EC 3.1.4.17) in these cells; the induction appears to be mediated by increases in intracellular cyclic AMP levels. These results indicate that this cell line might offer a system for studying the regulation of a type of cellular differentiation."}
{"id": "PMID:188044", "title": "Induction of mouse type-C virus by translational inhibitors: evidence for transcriptional derepression of a specific class of endogenous virus.", "content": "Several biologically distinguishable type-C RNA viruses are genetically transmitted in mouse cells. In the present report, chemicals that inhibit several different steps in protein synthesis are shown to cause marked increases in the cellular concentration of virus-specific RNA and the subsequent induction of virus. Analysis of the effect of translational inhibitors on mouse embryo cells of different genotypes indicates that activation of viral RNA is specific for one endogenous virus class and is a dominant genetic characteristic. Two lines of evidence favor the hypothesis that the induction of viral RNA involves transcriptional derepression rather than an alteration in its post-transcriptional processing. First, nuclear and cytoplasmic fractions of induced cells are shown to demonstrate similar increases in their concentrations of virus-specific RNA. Second, the decay of induced viral RNA following inhibition of further RNA synthesis by actinomycin D is not prevented by continued exposure to the inducer. These findings weigh heavily against the possibility that translational inhibitors act to stabilize viral RNA post-transcriptionally. The results are consistent with a model in which the expression of one class of endogenous virus is regulated by a labile repressor protein acting at a transcriptional level.", "contents": "Induction of mouse type-C virus by translational inhibitors: evidence for transcriptional derepression of a specific class of endogenous virus. Several biologically distinguishable type-C RNA viruses are genetically transmitted in mouse cells. In the present report, chemicals that inhibit several different steps in protein synthesis are shown to cause marked increases in the cellular concentration of virus-specific RNA and the subsequent induction of virus. Analysis of the effect of translational inhibitors on mouse embryo cells of different genotypes indicates that activation of viral RNA is specific for one endogenous virus class and is a dominant genetic characteristic. Two lines of evidence favor the hypothesis that the induction of viral RNA involves transcriptional derepression rather than an alteration in its post-transcriptional processing. First, nuclear and cytoplasmic fractions of induced cells are shown to demonstrate similar increases in their concentrations of virus-specific RNA. Second, the decay of induced viral RNA following inhibition of further RNA synthesis by actinomycin D is not prevented by continued exposure to the inducer. These findings weigh heavily against the possibility that translational inhibitors act to stabilize viral RNA post-transcriptionally. The results are consistent with a model in which the expression of one class of endogenous virus is regulated by a labile repressor protein acting at a transcriptional level."}
{"id": "PMID:188045", "title": "DNA-relaxing activity and endonuclease activity in Xenopus laevis oocytes.", "content": "Complex simian virus 40 DNA produced by a soluble cell-free extract derived from stage 6 oocytes of Xenopus laevis consists of fully relaxed circles (i.e., with no superhelical turns). An endonuclease and a DNA-relaxing protein, either or both of which could be responsible for the relaxation of the complex DNA, have been purified from the extract. The endonuclease(s) produces nicked circles (having a single-strand scission) and linear full-size molecules. The DNA-relaxing protein is in the nucleus, has a molecular weight of apporximately 70,000, and is able to remove both negative and positive superhelical turns.", "contents": "DNA-relaxing activity and endonuclease activity in Xenopus laevis oocytes. Complex simian virus 40 DNA produced by a soluble cell-free extract derived from stage 6 oocytes of Xenopus laevis consists of fully relaxed circles (i.e., with no superhelical turns). An endonuclease and a DNA-relaxing protein, either or both of which could be responsible for the relaxation of the complex DNA, have been purified from the extract. The endonuclease(s) produces nicked circles (having a single-strand scission) and linear full-size molecules. The DNA-relaxing protein is in the nucleus, has a molecular weight of apporximately 70,000, and is able to remove both negative and positive superhelical turns."}
{"id": "PMID:188046", "title": "An 18,000 molecular weight polypeptide induces early events and stimulates DNA synthesis in cultured cells.", "content": "Extracts of serum-free medium, conditioned by contact with SV40-transformed BHK cells, stimulate DNA synthesis in cultured fibroblasts. From this source, we have purified a homogenous basic protein of 18,000 molecular weight, termed fibroblast derived growth factor. In submicrogram quantities, fibroblast derived growth factor stimulates DNA synthesis in mouse 3T3 cells, in the absence of added serum. Prior to the onset of DNA synthesis, both serum and fibroblast derived growth factor induce an array of nearly simultaneous biochemical changes in the membrane to 3T3 cells that include stimulation of the uptake of nucleosides, 2-deoxyglucose, and 86Rb+. These results strongly suggest that the early events are integral components of the proliferative response, rather than coincidental effects of nonmitogenic molecules present in serum.", "contents": "An 18,000 molecular weight polypeptide induces early events and stimulates DNA synthesis in cultured cells. Extracts of serum-free medium, conditioned by contact with SV40-transformed BHK cells, stimulate DNA synthesis in cultured fibroblasts. From this source, we have purified a homogenous basic protein of 18,000 molecular weight, termed fibroblast derived growth factor. In submicrogram quantities, fibroblast derived growth factor stimulates DNA synthesis in mouse 3T3 cells, in the absence of added serum. Prior to the onset of DNA synthesis, both serum and fibroblast derived growth factor induce an array of nearly simultaneous biochemical changes in the membrane to 3T3 cells that include stimulation of the uptake of nucleosides, 2-deoxyglucose, and 86Rb+. These results strongly suggest that the early events are integral components of the proliferative response, rather than coincidental effects of nonmitogenic molecules present in serum."}
{"id": "PMID:188047", "title": "Prevention of spontaneous leukemia in AKR mice by type-specific immunosuppression of endogenous ecotropic virogenes.", "content": "AKR/J mice, 80-90% of which ordinarily die of spontaneous lymphocytic leukemias by 12 months of age, were significantly protected from developing leukemia in the initial experiment by a single course of treatment with AKR serotype-specific antibodies mad in goats and processed as immune gamma globulin (IgG). In experiment 1, IgG was given on the day of birth and on four additional days, and finished on day 14. This schedule resulted in suppression of over 4 logarithms of normal virogene expressions up to 25 days of age and led to partial viral suppression for over 200 days of age. At 365 days of age, 20 of 24 (83.3%) control animals were dead of leukemia whereas six of 30 (20%) treated animals had died of leukemia. In a second experiment, only four inoculations of IgG were given from birth to 20 days, after which they were given three inoculations of radiation-killed vaccine specific for AKR-Gross leukemia virus and one injection of murine sarcoma virus-Gross leukemia virus 10 days later. This combined immunization procedure provided significant virus suppression up to 288 days of age. At 300 days of age, 30 of the 50 (60%) controls had died of leukemia while only 1 of 24 (4.2%) of the immunized mice developed fatal leukemia; the significance of protection for each of the experiments was P LESS THAN 0.001. We conclude that these data establish in classical fashion with type-specific immunosuppression the determining role of type-C endogenous virogenes in leukemogenesis and, at the same time, also established the feasibility of nearly total prevention of leukemia in AKR mice.", "contents": "Prevention of spontaneous leukemia in AKR mice by type-specific immunosuppression of endogenous ecotropic virogenes. AKR/J mice, 80-90% of which ordinarily die of spontaneous lymphocytic leukemias by 12 months of age, were significantly protected from developing leukemia in the initial experiment by a single course of treatment with AKR serotype-specific antibodies mad in goats and processed as immune gamma globulin (IgG). In experiment 1, IgG was given on the day of birth and on four additional days, and finished on day 14. This schedule resulted in suppression of over 4 logarithms of normal virogene expressions up to 25 days of age and led to partial viral suppression for over 200 days of age. At 365 days of age, 20 of 24 (83.3%) control animals were dead of leukemia whereas six of 30 (20%) treated animals had died of leukemia. In a second experiment, only four inoculations of IgG were given from birth to 20 days, after which they were given three inoculations of radiation-killed vaccine specific for AKR-Gross leukemia virus and one injection of murine sarcoma virus-Gross leukemia virus 10 days later. This combined immunization procedure provided significant virus suppression up to 288 days of age. At 300 days of age, 30 of the 50 (60%) controls had died of leukemia while only 1 of 24 (4.2%) of the immunized mice developed fatal leukemia; the significance of protection for each of the experiments was P LESS THAN 0.001. We conclude that these data establish in classical fashion with type-specific immunosuppression the determining role of type-C endogenous virogenes in leukemogenesis and, at the same time, also established the feasibility of nearly total prevention of leukemia in AKR mice."}
{"id": "PMID:188048", "title": "Occurrence of BK virus DNA in DNA obtained from certain human tumors.", "content": "DNA sequences from BK virus have been detected by measurements of reassociation kinetics in DNA preparations isolated from five of 12 human tumor tissues and three of four human tumor cell lines; no DNA sequences from BK virus could be found using the same assay in DNA samples obtained from nontumor tissues removed from various patients. Whether or not this association is trivial, indicative of infection by BK virus, or correlative with the tumor state must await the testing of additional samples of normal and tumor tissues as well as a definition of the physical state of the genome of BK virus.", "contents": "Occurrence of BK virus DNA in DNA obtained from certain human tumors. DNA sequences from BK virus have been detected by measurements of reassociation kinetics in DNA preparations isolated from five of 12 human tumor tissues and three of four human tumor cell lines; no DNA sequences from BK virus could be found using the same assay in DNA samples obtained from nontumor tissues removed from various patients. Whether or not this association is trivial, indicative of infection by BK virus, or correlative with the tumor state must await the testing of additional samples of normal and tumor tissues as well as a definition of the physical state of the genome of BK virus."}
{"id": "PMID:188049", "title": "Hypophosphatemia: mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets.", "content": "A new dominant mutation in the laboratory mouse, hypophosphatemia (gene symbol Hyp), has been identified. The Hyp gene is located on the X-chromosome and maps at the distal end. Mutant mice are characterized by hypophosphatemia, bone changes resembling rickets, diminished bone ash, dwarfism, and high fractional excretion of phosphate anion (low net tubular reabsorption). Phosphate supplementation of the diet from wearning prevents the appearance of severe skeletal abnormalities. The hypophosphatemic male mouse resembles human males with X-linked hypophosphatemia and the Hyp gene is presemably homologous with the X-linked human gene. The mouse model should facilitate study of the defect in transport of plasma inorganic phosphate anion.", "contents": "Hypophosphatemia: mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets. A new dominant mutation in the laboratory mouse, hypophosphatemia (gene symbol Hyp), has been identified. The Hyp gene is located on the X-chromosome and maps at the distal end. Mutant mice are characterized by hypophosphatemia, bone changes resembling rickets, diminished bone ash, dwarfism, and high fractional excretion of phosphate anion (low net tubular reabsorption). Phosphate supplementation of the diet from wearning prevents the appearance of severe skeletal abnormalities. The hypophosphatemic male mouse resembles human males with X-linked hypophosphatemia and the Hyp gene is presemably homologous with the X-linked human gene. The mouse model should facilitate study of the defect in transport of plasma inorganic phosphate anion."}
{"id": "PMID:188050", "title": "Biological and serological characterization of radiation leukemia virus.", "content": "Radiation leukemia virus, isolated from radiation-induced lymphomas in C57BL/Ka mice and propagated in that strain, is thymotropic and leukemogenic in vivo but replicates poorly, if at all, in mouse and mink fibroblast cultures in vitro. Comparative studies indicate that this naturally occurring virus is distinct from the previously recognized classes of endogenous murine ecotropic and xenotropic C-type viruses which are capable of replication on fibroblasts (fibrotropic) but are neither thymotropic nor leukemogenic. These studies also demonstrate that a differentiation-specific restriction system governing the replication of the murine ecotropic C-type viruses operates in addition to the previously defined Fv-1 and SRV gene restriction systems.", "contents": "Biological and serological characterization of radiation leukemia virus. Radiation leukemia virus, isolated from radiation-induced lymphomas in C57BL/Ka mice and propagated in that strain, is thymotropic and leukemogenic in vivo but replicates poorly, if at all, in mouse and mink fibroblast cultures in vitro. Comparative studies indicate that this naturally occurring virus is distinct from the previously recognized classes of endogenous murine ecotropic and xenotropic C-type viruses which are capable of replication on fibroblasts (fibrotropic) but are neither thymotropic nor leukemogenic. These studies also demonstrate that a differentiation-specific restriction system governing the replication of the murine ecotropic C-type viruses operates in addition to the previously defined Fv-1 and SRV gene restriction systems."}
{"id": "PMID:188051", "title": "Changes in expression of murine leukemia virus antigens and production of xenotropic virus in the late preleukemic period in AKR mice.", "content": "We recently reported that thymocytes from 6-month-old preleukemic AKR mice express higher levels of murine leukemia virus (MuLV)-related antigens that thymocytes from 2-month-old mice. We have now found that the level of xenotropic MuLV (defined operationally as MuLV able to infect mink cell cultures) is also markedly increased in thymus of 6-month-old AKR mice and that this increase in virus correlates closely with increased MuLV-antigen expression. There is no increase of MuLV antigen or xenotropic virus in spleen or lymph nodes. Production of ecotropic MuLV remains unchanged with age in thymus, lymph nodes, and spleen. Thymic grafts from 6-month-old AKR mice, but not from 2-month-old mice, induce both amplified MuLV-antigen expression and xenotropic virus production in the thymus of young AKR recipients. Experiments with lethally irradiated AKR mice reconstituted with syngeneic bone marrow cells indicate that age-related changes in the thymus rather than in bone marrow precursor cells are responsible for MuLV-antigen amplification.", "contents": "Changes in expression of murine leukemia virus antigens and production of xenotropic virus in the late preleukemic period in AKR mice. We recently reported that thymocytes from 6-month-old preleukemic AKR mice express higher levels of murine leukemia virus (MuLV)-related antigens that thymocytes from 2-month-old mice. We have now found that the level of xenotropic MuLV (defined operationally as MuLV able to infect mink cell cultures) is also markedly increased in thymus of 6-month-old AKR mice and that this increase in virus correlates closely with increased MuLV-antigen expression. There is no increase of MuLV antigen or xenotropic virus in spleen or lymph nodes. Production of ecotropic MuLV remains unchanged with age in thymus, lymph nodes, and spleen. Thymic grafts from 6-month-old AKR mice, but not from 2-month-old mice, induce both amplified MuLV-antigen expression and xenotropic virus production in the thymus of young AKR recipients. Experiments with lethally irradiated AKR mice reconstituted with syngeneic bone marrow cells indicate that age-related changes in the thymus rather than in bone marrow precursor cells are responsible for MuLV-antigen amplification."}
{"id": "PMID:188052", "title": "Intraneuronal guanylyl-imidodiphosphate injection mimics long-term synaptic hyperpolarization in Aplysia.", "content": "The phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) inhibitor thepohylline enhances both the amplitude and duration of a long-lasting synaptic hyperpolarization in identified neuron R15 in Aplysia californica. Intraneuronal injection into R15 of glanylyl-imidodiphosphate, an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activator, results in a deep and long-lasting hyperpolarization of the cell, similar to that produced by synaptic stimulation. Biochemical analysis confirms that guanylyl-imidodiphosphate activates adenylate cyclase in Aplysia californica nervous tissue, without affecting phosphodiesterase activity. These observations suggest that adenosine 3':5'-cyclic monophosphate plays a role in long-lasting synaptic inhibition and are consistent with a post-synaptic site of action for adenosine 3':5'-cyclic monophosphate.", "contents": "Intraneuronal guanylyl-imidodiphosphate injection mimics long-term synaptic hyperpolarization in Aplysia. The phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17) inhibitor thepohylline enhances both the amplitude and duration of a long-lasting synaptic hyperpolarization in identified neuron R15 in Aplysia californica. Intraneuronal injection into R15 of glanylyl-imidodiphosphate, an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activator, results in a deep and long-lasting hyperpolarization of the cell, similar to that produced by synaptic stimulation. Biochemical analysis confirms that guanylyl-imidodiphosphate activates adenylate cyclase in Aplysia californica nervous tissue, without affecting phosphodiesterase activity. These observations suggest that adenosine 3':5'-cyclic monophosphate plays a role in long-lasting synaptic inhibition and are consistent with a post-synaptic site of action for adenosine 3':5'-cyclic monophosphate."}
{"id": "PMID:188053", "title": "Physical-chemical approach to the transient change in Na ion conductivity of excitable membranes.", "content": "A new method is proposed for analyzing the rapid transient current component (Na ions) in voltage clamp experiments on excitable membranes. The method is based on only two very general assumptions: the Na ion conductivity of an excitable membrane is determined by some general membrane parameter, the kinetic behavior of which is consistently described by the sum of only two simple exponential terms. A least square computer analysis for the data by L. Goldman and C.L. Schauf on Myxicola axons is described [(1973) J. Gen. Physiol. 61, 361-384]. The method gives (as a result) the relationship between conductivity and membrane parameter. A physically plausible, chemical model (cycle of three states) is proposed for a dissipative control of the Na ion conductivity. The rate constants for the specific model are calculated from kinetic parameters derived only from the general analysis. These rate constants reproduce the original voltage clamp data in every feature which includes peak current ratios (h infinity)-shift with test potential. By allowing for differences in the experimental conditions, we derive essentially the same rate constants for the voltage clamp data of A.L. Hodgkin and A.F. Huxley on squid giant axons.", "contents": "Physical-chemical approach to the transient change in Na ion conductivity of excitable membranes. A new method is proposed for analyzing the rapid transient current component (Na ions) in voltage clamp experiments on excitable membranes. The method is based on only two very general assumptions: the Na ion conductivity of an excitable membrane is determined by some general membrane parameter, the kinetic behavior of which is consistently described by the sum of only two simple exponential terms. A least square computer analysis for the data by L. Goldman and C.L. Schauf on Myxicola axons is described [(1973) J. Gen. Physiol. 61, 361-384]. The method gives (as a result) the relationship between conductivity and membrane parameter. A physically plausible, chemical model (cycle of three states) is proposed for a dissipative control of the Na ion conductivity. The rate constants for the specific model are calculated from kinetic parameters derived only from the general analysis. These rate constants reproduce the original voltage clamp data in every feature which includes peak current ratios (h infinity)-shift with test potential. By allowing for differences in the experimental conditions, we derive essentially the same rate constants for the voltage clamp data of A.L. Hodgkin and A.F. Huxley on squid giant axons."}
{"id": "PMID:188054", "title": "DDC-induced retrograde amnesias prevented by injections of dl-DOPS.", "content": "Injection of a dopamine beta-hydroxylate inhibitor, diethyldithiocarbamate (DDC) in rats 30 min prior to training of a step-down passive avoidance task impaired performance of the task 24 hr later. Similarly, injection of DDC 30 min prior to testing blocked retrieval of a passive avoidance habit trained in normal rats the previous day. Injection of a direct norepinephrine (NE) precursor, dl-thero 3,4-dihydroxyphenylserine (DOPS) 60 min before DDC prevented both amnesias. These data support the hypothesis that reduced levels of NE are responsible for DDC-induced amnesias.", "contents": "DDC-induced retrograde amnesias prevented by injections of dl-DOPS. Injection of a dopamine beta-hydroxylate inhibitor, diethyldithiocarbamate (DDC) in rats 30 min prior to training of a step-down passive avoidance task impaired performance of the task 24 hr later. Similarly, injection of DDC 30 min prior to testing blocked retrieval of a passive avoidance habit trained in normal rats the previous day. Injection of a direct norepinephrine (NE) precursor, dl-thero 3,4-dihydroxyphenylserine (DOPS) 60 min before DDC prevented both amnesias. These data support the hypothesis that reduced levels of NE are responsible for DDC-induced amnesias."}
{"id": "PMID:188056", "title": "Subcutaneous mastectomy data: a preliminary report.", "content": "This is a preliminary report on data accumulated in the first 12 months by the Subcutaneous Mastectomy Data Evaluation Center at Saint Francis Memorial Hospital in San Francisco, California. We present some statistics on 419 subcutaneous mastectomies performed by 105 plastic surgeons.", "contents": "Subcutaneous mastectomy data: a preliminary report. This is a preliminary report on data accumulated in the first 12 months by the Subcutaneous Mastectomy Data Evaluation Center at Saint Francis Memorial Hospital in San Francisco, California. We present some statistics on 419 subcutaneous mastectomies performed by 105 plastic surgeons."}
{"id": "PMID:188060", "title": "6-Hydroxydopamine and the aggressive behavior induced by marihuana in REM sleep-deprived rats.", "content": "6-Hydroxydopamine (6OH-DA) pretreatment increased the aggressive behavior induced by marihuana in REM sleep-deprived rats. Brain catecholamine assays revealed that 6OH-DA depleted popamine (DA) and norepinephrine (NE) to a different extent, increasing the DA/NE ratio. Intraventricular injection of NE significantly decreased the aggressive behavior of these animals, whereas control solution or DA injections had no effect. The possible role played by DA and NE in the aggressive behavior induced by marihuana in REM sleep-deprived rats is discussed.", "contents": "6-Hydroxydopamine and the aggressive behavior induced by marihuana in REM sleep-deprived rats. 6-Hydroxydopamine (6OH-DA) pretreatment increased the aggressive behavior induced by marihuana in REM sleep-deprived rats. Brain catecholamine assays revealed that 6OH-DA depleted popamine (DA) and norepinephrine (NE) to a different extent, increasing the DA/NE ratio. Intraventricular injection of NE significantly decreased the aggressive behavior of these animals, whereas control solution or DA injections had no effect. The possible role played by DA and NE in the aggressive behavior induced by marihuana in REM sleep-deprived rats is discussed."}
{"id": "PMID:188061", "title": "Pre- and post-junctional supersensitivity: differentiation by intraventricular infusions of norepinephrine and methoxamine.", "content": "Intraventricular infusions of methoxamine, an adrenergic agonist that has a relatively low affinity for the presynaptic uptake mechanism, produces a significant dose-dependent increase in locomotor activity comparable to the increase elicited by infusion of equimolar doses of norepinephrine (NE). The behavioral responsiveness to infusion of both NE and methoxamine was more than doubled 3 weeks after pretreatment with 6-hydroxydopamine (6-OHDA). These results indicate that the increased responsiveness to NE induced by 6-OHDA is due to enhanced postsynaptic receptor sensitivity rather than to a loss of presynaptic uptake inactivation.", "contents": "Pre- and post-junctional supersensitivity: differentiation by intraventricular infusions of norepinephrine and methoxamine. Intraventricular infusions of methoxamine, an adrenergic agonist that has a relatively low affinity for the presynaptic uptake mechanism, produces a significant dose-dependent increase in locomotor activity comparable to the increase elicited by infusion of equimolar doses of norepinephrine (NE). The behavioral responsiveness to infusion of both NE and methoxamine was more than doubled 3 weeks after pretreatment with 6-hydroxydopamine (6-OHDA). These results indicate that the increased responsiveness to NE induced by 6-OHDA is due to enhanced postsynaptic receptor sensitivity rather than to a loss of presynaptic uptake inactivation."}
{"id": "PMID:188062", "title": "Effect of desmethyldiazepam and chlordesmethyldiazepam on 3',5'-cyclic guanosine monophosphate levels in rat cerebellum.", "content": "Three different ben,odia,epines (diazepam, its pharmacologically active metabolite desmethyldiazepam, and the derivative chlordesmethyldiazepam) have been compared in our study for their effects on 3',5'-guanosine monophosphate (cGMP) cerebellar levels. Desmethyldiazepam and chlordesmethyldiazepam are several-fold more potent than diazepam in decreasing rat cyclic cGMP cerebellar concentrations. None of the three drugs induces detectable changes of cerebellar cyclic 3',5'-adenosine monophosphate (cAMP). On the other hand, the three compounds did not modify the levels of cGMP in cerebellum of newborn rats, where Purkinje cell and dendrites lack synaptic contacts. However, injection of gamma aminobutyric acid (GABA) in the newborn is still able, as in the adult, to decrease cGMP concentration in cerebellum. Our data support the hypothesis that cGMP cerebellar concentrations may be reliable biochemical marker of the clinical activity of benzodiazepines.", "contents": "Effect of desmethyldiazepam and chlordesmethyldiazepam on 3',5'-cyclic guanosine monophosphate levels in rat cerebellum. Three different ben,odia,epines (diazepam, its pharmacologically active metabolite desmethyldiazepam, and the derivative chlordesmethyldiazepam) have been compared in our study for their effects on 3',5'-guanosine monophosphate (cGMP) cerebellar levels. Desmethyldiazepam and chlordesmethyldiazepam are several-fold more potent than diazepam in decreasing rat cyclic cGMP cerebellar concentrations. None of the three drugs induces detectable changes of cerebellar cyclic 3',5'-adenosine monophosphate (cAMP). On the other hand, the three compounds did not modify the levels of cGMP in cerebellum of newborn rats, where Purkinje cell and dendrites lack synaptic contacts. However, injection of gamma aminobutyric acid (GABA) in the newborn is still able, as in the adult, to decrease cGMP concentration in cerebellum. Our data support the hypothesis that cGMP cerebellar concentrations may be reliable biochemical marker of the clinical activity of benzodiazepines."}
{"id": "PMID:188063", "title": "Long term results of venesection therapy in idiopathic haemochromatosis.", "content": "Observations on the clinical effects of venesection therapy in 85 treated, as compared with 26 untreated, patients with idiopathic haemochromatosis showed decreased pigmentation and hepatomegaly together with a return to normal tests of liver function in half the patients who had abnormal tests at presentation. Control improved in 28 per cent of those patients with diabetes mellitus, although some patients developed it during the period of observation, despite venesection. Portal hypertension, testicular atrophy and arthropathy were not improved. In only 12 patients was there sufficient reaccumulation of iron after the initial course of venesection to merit further treatment. Rates of iron accumulation in these patients varied between 1-4 mg and 4-8 mg per day and chelatable iron levels were noted to be inappropriately high in relation to body iron stores during the early stages of the reaccumulation period. Life table data shows that the percentage survival five and ten years after diagnosis was 66 and 32 per cent respectively for the treated patients, and 18 and 6 per cent respectively for the untreated patients, both statistically highly significant differences (p less than 0-01). Possible clinical differences such as age of presentation, the presence of diabetes mellitus, cirrhosis, clinical hepatic failure and hepatoma between the treated and untreated groups that might otherwise have weighted survival in favour of the treated group were corrected by the use of covariant analysis. This gave mean log survival values of 4-15 and 2-88 for the treated and untreated patients respectively, equivalent to 63-4 months and 17-8 months, a highly significant difference (p less than 0-01). Ten patients, all of whom had cirrhosis at the time of diagnosis, died of malignant hepatoma between three and 15 years after completing venesection therapy. There was also a high rate of death from neoplasms in a variety of other sites--22 per cent in the venesected group, strikingly higher than that rate predicted for a similarly aged population using national cancer mortality rates.", "contents": "Long term results of venesection therapy in idiopathic haemochromatosis. Observations on the clinical effects of venesection therapy in 85 treated, as compared with 26 untreated, patients with idiopathic haemochromatosis showed decreased pigmentation and hepatomegaly together with a return to normal tests of liver function in half the patients who had abnormal tests at presentation. Control improved in 28 per cent of those patients with diabetes mellitus, although some patients developed it during the period of observation, despite venesection. Portal hypertension, testicular atrophy and arthropathy were not improved. In only 12 patients was there sufficient reaccumulation of iron after the initial course of venesection to merit further treatment. Rates of iron accumulation in these patients varied between 1-4 mg and 4-8 mg per day and chelatable iron levels were noted to be inappropriately high in relation to body iron stores during the early stages of the reaccumulation period. Life table data shows that the percentage survival five and ten years after diagnosis was 66 and 32 per cent respectively for the treated patients, and 18 and 6 per cent respectively for the untreated patients, both statistically highly significant differences (p less than 0-01). Possible clinical differences such as age of presentation, the presence of diabetes mellitus, cirrhosis, clinical hepatic failure and hepatoma between the treated and untreated groups that might otherwise have weighted survival in favour of the treated group were corrected by the use of covariant analysis. This gave mean log survival values of 4-15 and 2-88 for the treated and untreated patients respectively, equivalent to 63-4 months and 17-8 months, a highly significant difference (p less than 0-01). Ten patients, all of whom had cirrhosis at the time of diagnosis, died of malignant hepatoma between three and 15 years after completing venesection therapy. There was also a high rate of death from neoplasms in a variety of other sites--22 per cent in the venesected group, strikingly higher than that rate predicted for a similarly aged population using national cancer mortality rates."}
{"id": "PMID:188064", "title": "Dysfibrinogenaemia and primary hepato-cellular carcinoma.", "content": "The mechanisms of blood coagulation and fibrinolysis have been evaluated in 28 black adult Africans with primary hepato-cellular carcinoma (HCC). A characteristic pattern of abnormalities has been defined. Dysfibrinogenaemia appears to be a useful biological marker for the disease. The reptilase test (RT) is a simple, reliable and sensitive means of detection of this metabolic abnormality. It is suggested that the RT should be used to screen populations at high risk of developing HCC, such as cirrhotics, in conjunction with alpha fetoprotein determinations, which, alone, are inadequate for the purpose. The haemostatic defect may have relevance to the pathogenesis of HCC, and further suggests a potentially useful, additional, therapeutic modality.", "contents": "Dysfibrinogenaemia and primary hepato-cellular carcinoma. The mechanisms of blood coagulation and fibrinolysis have been evaluated in 28 black adult Africans with primary hepato-cellular carcinoma (HCC). A characteristic pattern of abnormalities has been defined. Dysfibrinogenaemia appears to be a useful biological marker for the disease. The reptilase test (RT) is a simple, reliable and sensitive means of detection of this metabolic abnormality. It is suggested that the RT should be used to screen populations at high risk of developing HCC, such as cirrhotics, in conjunction with alpha fetoprotein determinations, which, alone, are inadequate for the purpose. The haemostatic defect may have relevance to the pathogenesis of HCC, and further suggests a potentially useful, additional, therapeutic modality."}
{"id": "PMID:188068", "title": "The bile ducts.", "content": "The common duct is a critical conduit. Hippocrates observed that to maintain health it is important to keep the yellow bile from the liver in balance. The present authors provide extensive descriptions of the structure, function, anomalies and disorders of the bile ducts, and make special note of the radiographic techniques available for use in diagnosis.", "contents": "The bile ducts. The common duct is a critical conduit. Hippocrates observed that to maintain health it is important to keep the yellow bile from the liver in balance. The present authors provide extensive descriptions of the structure, function, anomalies and disorders of the bile ducts, and make special note of the radiographic techniques available for use in diagnosis."}
{"id": "PMID:188069", "title": "Computed body tomography.", "content": "Only the surface of the diagnostic possibilities inherent in CT imaging has been scratched. Solic organ pathology is readily visible in most instances by computed tomography. With further extension of present knowledge and development of newer contrast agents, the ability of computed body tomography to image a wide range of diseases appears almost limitless.", "contents": "Computed body tomography. Only the surface of the diagnostic possibilities inherent in CT imaging has been scratched. Solic organ pathology is readily visible in most instances by computed tomography. With further extension of present knowledge and development of newer contrast agents, the ability of computed body tomography to image a wide range of diseases appears almost limitless."}
{"id": "PMID:188074", "title": "Phosphatidylethanolamide derivatives of prostaglandins E1 and E2.", "content": "Prostaglandins E1 (PGE1) and E2 (PGE2) have been coupled with the amine group of phosphatidylethanolamine (PE) by means of dicyclohexylcarbodiimide. These complexes basically mimic the relaxant and contractile effects of the corresponding free prostaglandins (PGs) on various smooth muscle preparations, but exhibit a delayed onset of action and a lower affinity for the PG receptors. The complexes are comparable with the free, parent PGs, in their intrinsic activities. The same holds true for the effects on blood pressure and on the motility of the uterus in situ. The PGE2-PE complex is hydrolysed to release obviously free PGE2 by cell-free homogenates prepared from various tissues, but not by blood plasma. The PGE2-PE complex is immunologically indistinguishable from the free PGE2.", "contents": "Phosphatidylethanolamide derivatives of prostaglandins E1 and E2. Prostaglandins E1 (PGE1) and E2 (PGE2) have been coupled with the amine group of phosphatidylethanolamine (PE) by means of dicyclohexylcarbodiimide. These complexes basically mimic the relaxant and contractile effects of the corresponding free prostaglandins (PGs) on various smooth muscle preparations, but exhibit a delayed onset of action and a lower affinity for the PG receptors. The complexes are comparable with the free, parent PGs, in their intrinsic activities. The same holds true for the effects on blood pressure and on the motility of the uterus in situ. The PGE2-PE complex is hydrolysed to release obviously free PGE2 by cell-free homogenates prepared from various tissues, but not by blood plasma. The PGE2-PE complex is immunologically indistinguishable from the free PGE2."}
{"id": "PMID:188075", "title": "Correlation between cyclic AMP and LH release following prostaglandin E2 administration.", "content": "Five min following a single iv injection of PGE2 into ovariectomized mature rats pretreated with estrogen and progesterone, plasma LH and plasma and pituitary cyclic AMP levels were raised significantly. A close correlation was observed between increased pituitary cyclic AMP contents and release of plasma LH. The average level of cyclic AMP in the anterior pituitary and plasma cyclic AMP increased significantly, while the circulating plasma LH level was not changed at 1 min after PGE2 injection. Plasma LH le-el increased at 2 min after PGE2 and reached a maximum level at the above-mentioned time. This is consistent with hypothesis that increased release of hormone is a consequence of increased pituitary cyclic AMP content.", "contents": "Correlation between cyclic AMP and LH release following prostaglandin E2 administration. Five min following a single iv injection of PGE2 into ovariectomized mature rats pretreated with estrogen and progesterone, plasma LH and plasma and pituitary cyclic AMP levels were raised significantly. A close correlation was observed between increased pituitary cyclic AMP contents and release of plasma LH. The average level of cyclic AMP in the anterior pituitary and plasma cyclic AMP increased significantly, while the circulating plasma LH level was not changed at 1 min after PGE2 injection. Plasma LH le-el increased at 2 min after PGE2 and reached a maximum level at the above-mentioned time. This is consistent with hypothesis that increased release of hormone is a consequence of increased pituitary cyclic AMP content."}
{"id": "PMID:188076", "title": "Comparison of luteolytic effectiveness of several prostaglandin analogs in heifers and relative binding affinity for bovine luteal prostaglandin binding sites.", "content": "The relative binding affinities for both the prostaglandin (PG)E1 and PGF2alpha specific bovine luteal binding sites were determined for five PGE and fourteen PGF derivatives and analogs. Relative binding affinity was determined in vitro using membranes prepared from bovine corpora luteal (CL) obtained from the slaughterhouse. The parent structure of the analog was a dominant feature in determining the affinity for the respective PG binding site. Luteolysis was determined in cattle following intramuscular injection of various doses of prostaglandin once between days 6 and 14 after estrus and measuring CL regression by ovarian palpation per rectum, interval between injection and return to estrus and duration of the subsequent estrous cycle. A dose which was luteolytic was established for each of eight PGF-type compounds, and a dose which was not luteolytic was also established. There appeared to be limited association between the relative affinity for the PGF2alpha specific site in vitro and the estimated luteolytic dose range of these PGF analogs when tested in cattle. Differences in in vivo luteolytic potency for the compounds tested could not be explained by differences in binding affinity. Differences in metabolism and absorption may also be important in the determination of in vivo potency.", "contents": "Comparison of luteolytic effectiveness of several prostaglandin analogs in heifers and relative binding affinity for bovine luteal prostaglandin binding sites. The relative binding affinities for both the prostaglandin (PG)E1 and PGF2alpha specific bovine luteal binding sites were determined for five PGE and fourteen PGF derivatives and analogs. Relative binding affinity was determined in vitro using membranes prepared from bovine corpora luteal (CL) obtained from the slaughterhouse. The parent structure of the analog was a dominant feature in determining the affinity for the respective PG binding site. Luteolysis was determined in cattle following intramuscular injection of various doses of prostaglandin once between days 6 and 14 after estrus and measuring CL regression by ovarian palpation per rectum, interval between injection and return to estrus and duration of the subsequent estrous cycle. A dose which was luteolytic was established for each of eight PGF-type compounds, and a dose which was not luteolytic was also established. There appeared to be limited association between the relative affinity for the PGF2alpha specific site in vitro and the estimated luteolytic dose range of these PGF analogs when tested in cattle. Differences in in vivo luteolytic potency for the compounds tested could not be explained by differences in binding affinity. Differences in metabolism and absorption may also be important in the determination of in vivo potency."}
{"id": "PMID:188079", "title": "[Interference associated with cell cultures chronical by infected with the Junin virus].", "content": "Supernatants from Vero cells persistently infected with Junin virus interfered with cytolitic and lethal activities of standard virus. Two Vero cell sublines, chronically infected with Junin virus named VRJ1 and VRJ3, were obtained after prolonged cultivation of cells which survived primary infection. VFJ1 was maintained over a period of 48 days, by biweekly serial transfers while VRJ3, similarly treated, was cultivated for 385 days. One of the characteristics of these cell lines was resistance against superinfection with homologous virus that ordinaily produced CPE and plaques in normal Vero cells; the cells were then considered chronically infected. Supernatants taken at different cell passage level were tested for its interference activity after centrifugation to eliminate floating cells and debris. The degree of CPE intensity caused by inoculation of Vero cells with 10(4), 10(5) or 10(6) TCID 50 of standard virus was markdely deppressed (Figure 1) by coinfection with supernatant from passage 3 of VRJ3 (VRJ1p1), VRJ1p1 supernatant also had interference activity as shown by coinfection with standard virus and expressed by plaque forming inhibition(Table 1). The plaque production of standard virus was inhibited by coinfection with VRJ1p1 supernatant which did not originate plaques when inoculated alone. The interference capacity of VRJ1p6 supernatant was reduced (Table 1) coincidentally with the formation of 55 PFU/ml. Interference activity was neutralized by Junin specific antiserum and inhibited by chloroform treatment. When Vero cells infected with VRJ1p6 supernatant were challenged with standard virus 72 hs later, an inhibition of 98% was achieved (Table 2) in contrast with value of 35% showed in Table 1.", "contents": "[Interference associated with cell cultures chronical by infected with the Junin virus]. Supernatants from Vero cells persistently infected with Junin virus interfered with cytolitic and lethal activities of standard virus. Two Vero cell sublines, chronically infected with Junin virus named VRJ1 and VRJ3, were obtained after prolonged cultivation of cells which survived primary infection. VFJ1 was maintained over a period of 48 days, by biweekly serial transfers while VRJ3, similarly treated, was cultivated for 385 days. One of the characteristics of these cell lines was resistance against superinfection with homologous virus that ordinaily produced CPE and plaques in normal Vero cells; the cells were then considered chronically infected. Supernatants taken at different cell passage level were tested for its interference activity after centrifugation to eliminate floating cells and debris. The degree of CPE intensity caused by inoculation of Vero cells with 10(4), 10(5) or 10(6) TCID 50 of standard virus was markdely deppressed (Figure 1) by coinfection with supernatant from passage 3 of VRJ3 (VRJ1p1), VRJ1p1 supernatant also had interference activity as shown by coinfection with standard virus and expressed by plaque forming inhibition(Table 1). The plaque production of standard virus was inhibited by coinfection with VRJ1p1 supernatant which did not originate plaques when inoculated alone. The interference capacity of VRJ1p6 supernatant was reduced (Table 1) coincidentally with the formation of 55 PFU/ml. Interference activity was neutralized by Junin specific antiserum and inhibited by chloroform treatment. When Vero cells infected with VRJ1p6 supernatant were challenged with standard virus 72 hs later, an inhibition of 98% was achieved (Table 2) in contrast with value of 35% showed in Table 1."}
{"id": "PMID:188087", "title": "Experimental challenge of pregnant gilts with swine influenza virus after vaccination.", "content": "Inactivated swine influenza virus was concentrated by filtration. Two 5 ml doses given subcutaneously two to three weeks apart to SPF gilts of breeding age of bred gilts was antigenic as measured by the hemagglutination-inhibition (HI) test. Higher HI titers of longer duration were produced in unvaccinated gilts after experimental challenge. Vaccinated gilts reverted to negative (less than 1:20) HI tests after challenge. Pigs from vaccinated gilts were heavier when weaned at five weeks of age than pigs from unvaccinated gilts. No swine influenza virus was isolated after challenge from placentas or pigs born dead or that died after farrowing.", "contents": "Experimental challenge of pregnant gilts with swine influenza virus after vaccination. Inactivated swine influenza virus was concentrated by filtration. Two 5 ml doses given subcutaneously two to three weeks apart to SPF gilts of breeding age of bred gilts was antigenic as measured by the hemagglutination-inhibition (HI) test. Higher HI titers of longer duration were produced in unvaccinated gilts after experimental challenge. Vaccinated gilts reverted to negative (less than 1:20) HI tests after challenge. Pigs from vaccinated gilts were heavier when weaned at five weeks of age than pigs from unvaccinated gilts. No swine influenza virus was isolated after challenge from placentas or pigs born dead or that died after farrowing."}
{"id": "PMID:188083", "title": "[The concept of risk in poliomyelitis (author's transl)].", "content": "In poliomyelitis the risk is of neurological accidents resulting either from the circulation of wild viruses (spontaneous risk) or from the introduction of virus-vaccine (vaccine risk). The spontaneous risk varies both according to the virus type and according to various factors which determine host resistance. Well known among these are: the intrinsic characteristics of the population at a given period (genetic factors and previous experiences of this population with poliomyelitis viruses); environmental factors (water supply, living conditions, rapid urbanization...) which are extremely variable among geographic zones, and cultural factors just as variable among populations. The vaccine risk involves two aspects: the risk of neurological accidents due to use of live vaccine, which has changed from the beginning of vaccination and risk of inefficacy due either to the vaccine itself, whether live or inactived or to temporary ill-understood unfitness of a vaccine to provoke an immunitary response. At the present time, spontaneous and vaccine risks are balanced only in the so called developed countries in which the vaccine risk is accepted as necessary to maintain the spontaneous risk at the lowest level.", "contents": "[The concept of risk in poliomyelitis (author's transl)]. In poliomyelitis the risk is of neurological accidents resulting either from the circulation of wild viruses (spontaneous risk) or from the introduction of virus-vaccine (vaccine risk). The spontaneous risk varies both according to the virus type and according to various factors which determine host resistance. Well known among these are: the intrinsic characteristics of the population at a given period (genetic factors and previous experiences of this population with poliomyelitis viruses); environmental factors (water supply, living conditions, rapid urbanization...) which are extremely variable among geographic zones, and cultural factors just as variable among populations. The vaccine risk involves two aspects: the risk of neurological accidents due to use of live vaccine, which has changed from the beginning of vaccination and risk of inefficacy due either to the vaccine itself, whether live or inactived or to temporary ill-understood unfitness of a vaccine to provoke an immunitary response. At the present time, spontaneous and vaccine risks are balanced only in the so called developed countries in which the vaccine risk is accepted as necessary to maintain the spontaneous risk at the lowest level."}
{"id": "PMID:188090", "title": "[Facial paralysis with inverse autonomic-voluntary dissociation from a frontal lesion. Cortical origin. Relation to supplementary motor area].", "content": "As a result of 6 cases of frontal tumour presenting central facial paralysis with inverse dissociation this symptom was investigated in patients subjected to cortical excisions for intractable epielpsy. A study of 8 cases of frontal cortical excision, 6 of them affecting the internal and posterior portion, and two the prefrontal region, has provided evidence of a link between inverse automatic-voluntary dissociation facial paralysis and lesions affecting the Penfield supplementary motor area. In such cases, facial palsy is usually associated with motor disorders in the limbs, the most characteristic of which is unilateral motor under-utilisation. The possibility of inverse dissociated facial paralysis occurring as a result of a rostral premotor lesion cannot be ruled out in our present state of knowledge.", "contents": "[Facial paralysis with inverse autonomic-voluntary dissociation from a frontal lesion. Cortical origin. Relation to supplementary motor area]. As a result of 6 cases of frontal tumour presenting central facial paralysis with inverse dissociation this symptom was investigated in patients subjected to cortical excisions for intractable epielpsy. A study of 8 cases of frontal cortical excision, 6 of them affecting the internal and posterior portion, and two the prefrontal region, has provided evidence of a link between inverse automatic-voluntary dissociation facial paralysis and lesions affecting the Penfield supplementary motor area. In such cases, facial palsy is usually associated with motor disorders in the limbs, the most characteristic of which is unilateral motor under-utilisation. The possibility of inverse dissociated facial paralysis occurring as a result of a rostral premotor lesion cannot be ruled out in our present state of knowledge."}
{"id": "PMID:188091", "title": "[Neurologic manifestations in Mycoplasma pneumoniae. Apropos of 12 cases].", "content": "Specific serological methods now enable us to demonstrate that Mycoplasma Pneumoniae is responsible for a variety of neurological symptoms. We describe 12 new cases: 2 encephalites, 8 diffuse polyradiculoneurites and 2 isolated lesions of the cranial nerves. These 12 cases, together with the 42 recorded in the literature, bring total number of published cases to 54. Analysis emphasizes the extreme polymorphism of the neurological manifestations and their favourable prognosis in most cases, however serious the initial symptoms. Although the pathogenesis of neurological symptoms produced by Mycoplasma Pneumoniae is still debatable, evidence supports an immunoallergic reaction.", "contents": "[Neurologic manifestations in Mycoplasma pneumoniae. Apropos of 12 cases]. Specific serological methods now enable us to demonstrate that Mycoplasma Pneumoniae is responsible for a variety of neurological symptoms. We describe 12 new cases: 2 encephalites, 8 diffuse polyradiculoneurites and 2 isolated lesions of the cranial nerves. These 12 cases, together with the 42 recorded in the literature, bring total number of published cases to 54. Analysis emphasizes the extreme polymorphism of the neurological manifestations and their favourable prognosis in most cases, however serious the initial symptoms. Although the pathogenesis of neurological symptoms produced by Mycoplasma Pneumoniae is still debatable, evidence supports an immunoallergic reaction."}
{"id": "PMID:188095", "title": "[Can radiophotographic detection be discontinued in rural areas at the current stage in Rumania?].", "content": "Considering the fact that in the rural environment the population groups at great risk are not sufficiently well known, in the case of tuberculosis, it is recommended that 1 or 2 more integral detection operations be carried out in this environment and to carry out a detailed investigation of the differentiated risk of various population groups.", "contents": "[Can radiophotographic detection be discontinued in rural areas at the current stage in Rumania?]. Considering the fact that in the rural environment the population groups at great risk are not sufficiently well known, in the case of tuberculosis, it is recommended that 1 or 2 more integral detection operations be carried out in this environment and to carry out a detailed investigation of the differentiated risk of various population groups."}
{"id": "PMID:188096", "title": "[Epidemiological and statistical problems in tubercular meningitis in children. (Observations during 1955-1974 period in the Satu-Mare district)].", "content": "The progressive decrease of the frequency of tuberculous meningitis in children will lead in the near future to the elimination of this type of localization, as a result of elimination of chronic focuses, achieved by strictly supervised treatment. The rare cases observed in the last years are due either to well-established contacts (parents, grandparents, neighbours), or to sporadic or even unique contacts with chronic cases.", "contents": "[Epidemiological and statistical problems in tubercular meningitis in children. (Observations during 1955-1974 period in the Satu-Mare district)]. The progressive decrease of the frequency of tuberculous meningitis in children will lead in the near future to the elimination of this type of localization, as a result of elimination of chronic focuses, achieved by strictly supervised treatment. The rare cases observed in the last years are due either to well-established contacts (parents, grandparents, neighbours), or to sporadic or even unique contacts with chronic cases."}
{"id": "PMID:188097", "title": "[Aspects of integral anti-tuberculosis chemotherapy in 15 rural medical stations of the Constan\u0163a district].", "content": "The study of aspects of integration of chemotherapy during the initial stages of the anti-tuberculous treatment, carried out in 15 rural medical circumscriptions in the Constantza and mpedgidia anti-tuberculous dispensaries, has demonstrated the applicability of standardized chemotherapy schemes at the level of general practice network. The personnel working in the frame of this network showed considerable interest and preoccupation with the optimal achievement of the strictly supervised treatment. The results of bacteriological controls (direct BK examination and cultures), indicated that in 97,4% of the cases these results are maintained negative in patients that could be evaluated. An assessment of this action revealed that the indices showing the incorporation of patients in the strictly supervised treatment as well as the regularity of the administration have been very good.", "contents": "[Aspects of integral anti-tuberculosis chemotherapy in 15 rural medical stations of the Constan\u0163a district]. The study of aspects of integration of chemotherapy during the initial stages of the anti-tuberculous treatment, carried out in 15 rural medical circumscriptions in the Constantza and mpedgidia anti-tuberculous dispensaries, has demonstrated the applicability of standardized chemotherapy schemes at the level of general practice network. The personnel working in the frame of this network showed considerable interest and preoccupation with the optimal achievement of the strictly supervised treatment. The results of bacteriological controls (direct BK examination and cultures), indicated that in 97,4% of the cases these results are maintained negative in patients that could be evaluated. An assessment of this action revealed that the indices showing the incorporation of patients in the strictly supervised treatment as well as the regularity of the administration have been very good."}
{"id": "PMID:188098", "title": "[Investigation of some risk factors in tubercular infection in children].", "content": "A total of 2057 children, from a village with an isolated farm of tuberculous cattle have been classified in the following groups: A--1843 children from healthy families; B--140 children whose parents were working at the bovine farm; C--70 tb contacts, and D--4 children with parents working at the farm and relatives suffering with tuberculosis. All were skin tested simultaneously with 1 and 10 PPD units. Milk was brought home from the farm by those who worked there, that was used without boiling. A total of 14,5% of all the children had a reaction of more than 5 mm to one PPD unit. The percentages were of 8,4 in group A 52,1 in group B and 94,3 in group C (P less than 0,001). Incidence of more than 9 mm reactions was of 5% in group A, 45% in group B and 91,4% in group C (P less than 0,001). The mean diameter for one PPD unit was of 1,1 mm in group A, 7,58 mm in group B and 15,88 mm in group C (P less than 0,001). The major risk factor is represented by the tuberculous patients, but use of milk, or of milk derivatives from diseased cattle could also be incriminated. Synchronous neutralization of these two sources of contamination remains the primary action to be carried out for the prevention of the tuberculous infection dissemination.", "contents": "[Investigation of some risk factors in tubercular infection in children]. A total of 2057 children, from a village with an isolated farm of tuberculous cattle have been classified in the following groups: A--1843 children from healthy families; B--140 children whose parents were working at the bovine farm; C--70 tb contacts, and D--4 children with parents working at the farm and relatives suffering with tuberculosis. All were skin tested simultaneously with 1 and 10 PPD units. Milk was brought home from the farm by those who worked there, that was used without boiling. A total of 14,5% of all the children had a reaction of more than 5 mm to one PPD unit. The percentages were of 8,4 in group A 52,1 in group B and 94,3 in group C (P less than 0,001). Incidence of more than 9 mm reactions was of 5% in group A, 45% in group B and 91,4% in group C (P less than 0,001). The mean diameter for one PPD unit was of 1,1 mm in group A, 7,58 mm in group B and 15,88 mm in group C (P less than 0,001). The major risk factor is represented by the tuberculous patients, but use of milk, or of milk derivatives from diseased cattle could also be incriminated. Synchronous neutralization of these two sources of contamination remains the primary action to be carried out for the prevention of the tuberculous infection dissemination."}
{"id": "PMID:188099", "title": "[Obstructive syndrome in laryngotracheal stenosis].", "content": "Pulmonary function studies were carried out in 13 patients in whom the diagnosis of a central (laryngeal or tracheal) stenosis was confirmed by endoscopy. Following lung function tests were performed: static lung volumes (VC, RV, TLC), FEV1.0 and FIV1.0, flow-volume loops of forced expiratory and forced inspiratory vital capacity efforts from which PEFR and PIFR, maximal expiratory (VEmx50) and maximal inspiratory flow at 50 per cent of vital capacity (VLmx50) were measured, Raw, helium mixing time and pharmacological test with acethylcholine. FIV1.0 values and flow-volume loops permitted the classification of the patients into 3 groups: 1. fixed obstruction (6 cases): decrease in about equal proportions of maximal expiratory and inspiratory flows (FEV1.0 and FIV1.0); normal FEV1.0/FIV1.0 ratio; 2. extrathoracic variable obstruction (1 case): predominant decrease in maximal inspiratory flows (FIV1.0). FEV1.0/FIV1.0 ratio is twice as normal; 3. intrathoracic variable obstruction (5 cases): exclusive or predominant reduction in maximal expiratory flows, as in COPD but with the difference that the expiratory limb of the V:V loop showed an excessive reduction in PEFR, a plateau in the midzone of the VC and a terminal portion with normal configuration. Raw was almost always increased, RV sometimes, helium mixing time was prolonged only in presence of COPD or lobar stenosis; pharmacological tests were negative in 3 out of 4 cases. Pulmonary function abnormalities did not allow a prognosis of the nature of the underlying lesion. The severity of the obstruction as evaluated by endoscopic examination was not related to the functional disturbances. In one case no functional alterations were found despite a severe tracheal stenosis.", "contents": "[Obstructive syndrome in laryngotracheal stenosis]. Pulmonary function studies were carried out in 13 patients in whom the diagnosis of a central (laryngeal or tracheal) stenosis was confirmed by endoscopy. Following lung function tests were performed: static lung volumes (VC, RV, TLC), FEV1.0 and FIV1.0, flow-volume loops of forced expiratory and forced inspiratory vital capacity efforts from which PEFR and PIFR, maximal expiratory (VEmx50) and maximal inspiratory flow at 50 per cent of vital capacity (VLmx50) were measured, Raw, helium mixing time and pharmacological test with acethylcholine. FIV1.0 values and flow-volume loops permitted the classification of the patients into 3 groups: 1. fixed obstruction (6 cases): decrease in about equal proportions of maximal expiratory and inspiratory flows (FEV1.0 and FIV1.0); normal FEV1.0/FIV1.0 ratio; 2. extrathoracic variable obstruction (1 case): predominant decrease in maximal inspiratory flows (FIV1.0). FEV1.0/FIV1.0 ratio is twice as normal; 3. intrathoracic variable obstruction (5 cases): exclusive or predominant reduction in maximal expiratory flows, as in COPD but with the difference that the expiratory limb of the V:V loop showed an excessive reduction in PEFR, a plateau in the midzone of the VC and a terminal portion with normal configuration. Raw was almost always increased, RV sometimes, helium mixing time was prolonged only in presence of COPD or lobar stenosis; pharmacological tests were negative in 3 out of 4 cases. Pulmonary function abnormalities did not allow a prognosis of the nature of the underlying lesion. The severity of the obstruction as evaluated by endoscopic examination was not related to the functional disturbances. In one case no functional alterations were found despite a severe tracheal stenosis."}
{"id": "PMID:188100", "title": "[Clinico-functional correlations in chronic obstructive bronchopneumopathy: dyspnea and arterial oxygenation].", "content": "The severity of dyspnoea was confronted to the value of the partial pressure of arterial oxygen at rest in a group of 51 patients with chronic non-specific pneumopathy associated to medium or severe ventilatory obstruction (VEMS under 1,5 I). The patients have been classified as \"predominantly bronchitic\" or \"predominantly emphysematous\" on the basis of clinical, radiological and biological criteria. In the group as a whole there was no relation between the partial pressure of arterial oxygen and the severity of the dyspnoea. The analysis of sub-groups evidenced a tendency to decrease of the oxygen pressure with accentuation of dyspnoea in the \"bronchitis\" group, although the coefficient value of this inverse correlation did not reach the treshold of statistical significance (r = -0,46; p greater than 0,05).", "contents": "[Clinico-functional correlations in chronic obstructive bronchopneumopathy: dyspnea and arterial oxygenation]. The severity of dyspnoea was confronted to the value of the partial pressure of arterial oxygen at rest in a group of 51 patients with chronic non-specific pneumopathy associated to medium or severe ventilatory obstruction (VEMS under 1,5 I). The patients have been classified as \"predominantly bronchitic\" or \"predominantly emphysematous\" on the basis of clinical, radiological and biological criteria. In the group as a whole there was no relation between the partial pressure of arterial oxygen and the severity of the dyspnoea. The analysis of sub-groups evidenced a tendency to decrease of the oxygen pressure with accentuation of dyspnoea in the \"bronchitis\" group, although the coefficient value of this inverse correlation did not reach the treshold of statistical significance (r = -0,46; p greater than 0,05)."}
{"id": "PMID:188102", "title": "[Cured chronic pulmonary tuberculosis].", "content": "The application of RMP and EMB in the treatment of chronic tuberculosis results in massive and durable sputum conversion, objectivated by the decreased prevalence of chronic cases and increase in the number of cured chronic patients, which impose a differentiated type of dispensarization. The presence of the post-tuberculous syndrome requires qualified pneumological assistance; the authors suggest that cured chronic patients be maintained in a supervised group for the rest of their lives. The cured chronic patient with tuberculosis should remain the major preoccupation of the anti-tuberculous dispensary, in the frame of the ambulatory pneumological assistance.", "contents": "[Cured chronic pulmonary tuberculosis]. The application of RMP and EMB in the treatment of chronic tuberculosis results in massive and durable sputum conversion, objectivated by the decreased prevalence of chronic cases and increase in the number of cured chronic patients, which impose a differentiated type of dispensarization. The presence of the post-tuberculous syndrome requires qualified pneumological assistance; the authors suggest that cured chronic patients be maintained in a supervised group for the rest of their lives. The cured chronic patient with tuberculosis should remain the major preoccupation of the anti-tuberculous dispensary, in the frame of the ambulatory pneumological assistance."}
{"id": "PMID:188101", "title": "[Comparative serum and secretory IgA studies in recurrent bronchial infections (preliminary note)].", "content": "In a group of 84 patients with recidivating bronchial infections IgA were evaluated with the aid of radial immunodiffusion according to Mancini. In all the patients IgA were determined from expectoration extractions and in 50 of them serum IgA were also determined. In 38 cases the determinations were simultaneous. Concentration of S IgA was low in most of the cases (65%). These results are probably influenced by the technical difficulties raised by detaching the connections existing between S IgA and mucus fibrils from the bronchial secretion. The results obtained in the dosage of serum IgA are comparable with those mentioned in the current literature. No correlations were possible between S IgA and serum IgA and there proteins can be considered as independent.", "contents": "[Comparative serum and secretory IgA studies in recurrent bronchial infections (preliminary note)]. In a group of 84 patients with recidivating bronchial infections IgA were evaluated with the aid of radial immunodiffusion according to Mancini. In all the patients IgA were determined from expectoration extractions and in 50 of them serum IgA were also determined. In 38 cases the determinations were simultaneous. Concentration of S IgA was low in most of the cases (65%). These results are probably influenced by the technical difficulties raised by detaching the connections existing between S IgA and mucus fibrils from the bronchial secretion. The results obtained in the dosage of serum IgA are comparable with those mentioned in the current literature. No correlations were possible between S IgA and serum IgA and there proteins can be considered as independent."}
{"id": "PMID:188103", "title": "[Severe complications following intermittent administration of rifampicin].", "content": "In the last two years the authors have noted the cases of five patients with pulmonary tuberculosis to which intermittent treatment with Rifampicin was administered (twice weekly, 600-900 mg/day), in association with Ethambutol. Between 2 and 6 months after the treatment was started, 24-72 hours after the last administration of Rifampicin acute renal failure developed in all five cases. Two of the patients also had signs of liver failure (increased serum transaminase, lowered pseudo-cholinesterase, increased BSP retention), and in one of them there was also a hematological syndrome consisting in hemolytic anemia and thrombocytopenia. Four of the patients benefited from application of diuretics, hydroelectrolytic re-equilibration and/or hemodialysis. One of the subjects died 12 hours after being hospitalized, with acute pulmonary oedema, refractory to treatment. From the histopathological viewpoint glomerular lesions were found in the kidney (non-uniform thickening of the basal membranes by PAS-positive deposits). In two of the patients various immunological tests have been carried out (Coombs test, lymphocyte-migration inhibition, serum and urine immunelectrophoresis) that, by their alterations, provide some elements indicating the immunological origin of the phenomena.", "contents": "[Severe complications following intermittent administration of rifampicin]. In the last two years the authors have noted the cases of five patients with pulmonary tuberculosis to which intermittent treatment with Rifampicin was administered (twice weekly, 600-900 mg/day), in association with Ethambutol. Between 2 and 6 months after the treatment was started, 24-72 hours after the last administration of Rifampicin acute renal failure developed in all five cases. Two of the patients also had signs of liver failure (increased serum transaminase, lowered pseudo-cholinesterase, increased BSP retention), and in one of them there was also a hematological syndrome consisting in hemolytic anemia and thrombocytopenia. Four of the patients benefited from application of diuretics, hydroelectrolytic re-equilibration and/or hemodialysis. One of the subjects died 12 hours after being hospitalized, with acute pulmonary oedema, refractory to treatment. From the histopathological viewpoint glomerular lesions were found in the kidney (non-uniform thickening of the basal membranes by PAS-positive deposits). In two of the patients various immunological tests have been carried out (Coombs test, lymphocyte-migration inhibition, serum and urine immunelectrophoresis) that, by their alterations, provide some elements indicating the immunological origin of the phenomena."}
{"id": "PMID:188108", "title": "[Current incidence of tubercular infection in children in the Dolj district].", "content": "A lot of 122459 children under the age of 14 were tested intradermally with 2 U PPD. Most of them had been vaccinated at birth and some revaccinated later during the 1966-1967 period, which does not represent interpretation of the prevalance of tuberculosis today, bearing in mind the low postvaccinal allergy of young children and the interval after the last vaccination, only the children with a reaction of more than 10 mm in diameter were taken into consideration as they represented the highest probability of the actual spread of the infection. In the age group up to 6 years 6.82% of the children were infected and 17.12% of the school children of grades II to VIII, i.e. less than the mean values recorded in the whole country. This was attributed to the intensive specific chemotherapy applied within the area. The prevalence gradually increased from 3.93% at the age of l year to 4.90% at 3 years, then sharply to 6.93% at 4 years (when the child's relations are extended) and 10.46% at 5 years. The proportion of infections was of 12--13% in grades II--IV (7-9 years), 16.63% in grade V, 20% in grade VI and 23.21% in grade VIII (13-14 years). The present values are much lower than those recorded in 1966. The present risk of infection is of 1%, with an annual decrease rate of 7%, starting in 1956. By comparison with the published data it is considered that neutralization by chemotherapy of all bacilli carriers will accelerate the rate of decrease of infection.", "contents": "[Current incidence of tubercular infection in children in the Dolj district]. A lot of 122459 children under the age of 14 were tested intradermally with 2 U PPD. Most of them had been vaccinated at birth and some revaccinated later during the 1966-1967 period, which does not represent interpretation of the prevalance of tuberculosis today, bearing in mind the low postvaccinal allergy of young children and the interval after the last vaccination, only the children with a reaction of more than 10 mm in diameter were taken into consideration as they represented the highest probability of the actual spread of the infection. In the age group up to 6 years 6.82% of the children were infected and 17.12% of the school children of grades II to VIII, i.e. less than the mean values recorded in the whole country. This was attributed to the intensive specific chemotherapy applied within the area. The prevalence gradually increased from 3.93% at the age of l year to 4.90% at 3 years, then sharply to 6.93% at 4 years (when the child's relations are extended) and 10.46% at 5 years. The proportion of infections was of 12--13% in grades II--IV (7-9 years), 16.63% in grade V, 20% in grade VI and 23.21% in grade VIII (13-14 years). The present values are much lower than those recorded in 1966. The present risk of infection is of 1%, with an annual decrease rate of 7%, starting in 1956. By comparison with the published data it is considered that neutralization by chemotherapy of all bacilli carriers will accelerate the rate of decrease of infection."}
{"id": "PMID:188107", "title": "[Chemotherapy of the source and the risk of infection in home contacts].", "content": "An attack treatment with 3 drugs during 4-6 months and a consolidation treatment with 2 drugs then INH was applied in 595 cases detected between July 1, 1968 and June 30, 1972, i.e. 264 group A (positive), 200 group B (negative cultures) and 131 group C (pleuretics). The contacts had been in close contact with the source for at least three months before establishing the diagnosis; 549 had been vaccinated at birth with BCG and 209 revaccinated; 413 had undergone chemoprophylaxis with INH.  The control group comprised 1008 subjects, the mean age of the groups being very close; they were followed up for 2 years and 1 month and 2 years and 7 months.  Testing was done every year with 1 u PPD IC 65. The contacts were controlled annually by radiophotography and X-ray and the controls only in case of shifting of the test. Among the contacts there were 44 conversions in the subjects with an initial tuberculin reaction of 0-5 mm and 4 in those with an initial tuberculin reaction of 6-9 mm, representing 15.1% (group A 27.7%, group B 9,8%, group C 10.5%). Three months after the initiation of chemotherapy the proportion of conversions in the three groups (group A 12.3%, group B 5.9%, group C 10.5%) was equal to that of the controls (8.8%). The next year there were 11.2% conversions among the contracts (group A 11.4%, group B 9.6% and C 17.7%) as against 11.9% among the controls. In the first year 8.3% of the contacts contracted tuberculosis (A 15.6%, B 2.4%, C 4.0%) and 0.32% of the controls. The next year 2.8% of the  contacts fell ill (A 4.3%, B 2%, C 0%) and 0.5% of the controls. Among group A contacts aged 0 to 6 years there were 31.7% conversions and 30.7% cases of tuberculosis in the first year, and 7.1% and 1.8% respectively in the following year. Group B and C presented 10.9% conversions and 6% cases of disease in the first year, and no case of tuberculosis in the second year. Chemotherapy reduced conversions and sickness in this group three months after the diagnosis was established.", "contents": "[Chemotherapy of the source and the risk of infection in home contacts]. An attack treatment with 3 drugs during 4-6 months and a consolidation treatment with 2 drugs then INH was applied in 595 cases detected between July 1, 1968 and June 30, 1972, i.e. 264 group A (positive), 200 group B (negative cultures) and 131 group C (pleuretics). The contacts had been in close contact with the source for at least three months before establishing the diagnosis; 549 had been vaccinated at birth with BCG and 209 revaccinated; 413 had undergone chemoprophylaxis with INH.  The control group comprised 1008 subjects, the mean age of the groups being very close; they were followed up for 2 years and 1 month and 2 years and 7 months.  Testing was done every year with 1 u PPD IC 65. The contacts were controlled annually by radiophotography and X-ray and the controls only in case of shifting of the test. Among the contacts there were 44 conversions in the subjects with an initial tuberculin reaction of 0-5 mm and 4 in those with an initial tuberculin reaction of 6-9 mm, representing 15.1% (group A 27.7%, group B 9,8%, group C 10.5%). Three months after the initiation of chemotherapy the proportion of conversions in the three groups (group A 12.3%, group B 5.9%, group C 10.5%) was equal to that of the controls (8.8%). The next year there were 11.2% conversions among the contracts (group A 11.4%, group B 9.6% and C 17.7%) as against 11.9% among the controls. In the first year 8.3% of the contacts contracted tuberculosis (A 15.6%, B 2.4%, C 4.0%) and 0.32% of the controls. The next year 2.8% of the  contacts fell ill (A 4.3%, B 2%, C 0%) and 0.5% of the controls. Among group A contacts aged 0 to 6 years there were 31.7% conversions and 30.7% cases of tuberculosis in the first year, and 7.1% and 1.8% respectively in the following year. Group B and C presented 10.9% conversions and 6% cases of disease in the first year, and no case of tuberculosis in the second year. Chemotherapy reduced conversions and sickness in this group three months after the diagnosis was established."}
{"id": "PMID:188106", "title": "[Reducing the risk of tuberculosis in children vaccinated with BCG].", "content": "In 1973, of 1774192 children aged 18 months to 6 years, 82,2% had to be revaccinated with BCG, 10.7% presented tuberculin reactions larger than 10 mm and 7.1% were absentees. In 1974 a number of 485 children belonging to the respective age group contracted tuberculosis. Analysis of these cases showed that the risk of tuberculosis was of 10.9 per 100,000 revaccinated subjects and of 74.6 per 10,000 absentees.  BCG vaccination not only lowered the risk of the disease but also reduced the risk of a severe evolution and death.", "contents": "[Reducing the risk of tuberculosis in children vaccinated with BCG]. In 1973, of 1774192 children aged 18 months to 6 years, 82,2% had to be revaccinated with BCG, 10.7% presented tuberculin reactions larger than 10 mm and 7.1% were absentees. In 1974 a number of 485 children belonging to the respective age group contracted tuberculosis. Analysis of these cases showed that the risk of tuberculosis was of 10.9 per 100,000 revaccinated subjects and of 74.6 per 10,000 absentees.  BCG vaccination not only lowered the risk of the disease but also reduced the risk of a severe evolution and death."}
{"id": "PMID:188109", "title": "[Intradermal BCG vaccination of the ,ewborn in the 1972-1975 period].", "content": "The study included 1015 children vaccinated BCG at birth in the \"Gh. Marinescu\" Maternity Hospital of Bucharest during the 1972-1975 period. The Romanian lyophilized BCG vaccine prepared in sodium glutamate in doses of 0.10 mg/0.1 ml was used. Of these children 543 were vaccinated in the Maternity Hospital and 472 by the vaccination teams of the Institute of Phthisiology, Bucharest. During the first two years 660 of these children were controlled at various intervals. Sensitivity to 2 U PPD was moderate during the first year, the mean diameter being of 4-5.3 mm in the children vaccinated before discharged from hospital and of 3.5-6.7 mm in diameter in the children vaccinated after discharge. At the age of 1 and 2 years the mean diameter did not exceed 3 mm. The vaccinal scar was present in more than 95% of the children in the first year, the mean diameter ranging between 3.6 and 4.8 mm. No postvaccinal complications were recorded. The authors consider that the results obtained can be taken as criteria for assessing the operational and technical effectiveness of BCG in neonates.", "contents": "[Intradermal BCG vaccination of the ,ewborn in the 1972-1975 period]. The study included 1015 children vaccinated BCG at birth in the \"Gh. Marinescu\" Maternity Hospital of Bucharest during the 1972-1975 period. The Romanian lyophilized BCG vaccine prepared in sodium glutamate in doses of 0.10 mg/0.1 ml was used. Of these children 543 were vaccinated in the Maternity Hospital and 472 by the vaccination teams of the Institute of Phthisiology, Bucharest. During the first two years 660 of these children were controlled at various intervals. Sensitivity to 2 U PPD was moderate during the first year, the mean diameter being of 4-5.3 mm in the children vaccinated before discharged from hospital and of 3.5-6.7 mm in diameter in the children vaccinated after discharge. At the age of 1 and 2 years the mean diameter did not exceed 3 mm. The vaccinal scar was present in more than 95% of the children in the first year, the mean diameter ranging between 3.6 and 4.8 mm. No postvaccinal complications were recorded. The authors consider that the results obtained can be taken as criteria for assessing the operational and technical effectiveness of BCG in neonates."}
{"id": "PMID:188110", "title": "[Contribution of pulmonary scintiscanning to the diagnosis of chronic obstructive bronchopneumopathy].", "content": "In a lot of 32 cases of chronic obstructive bronchopneumopathy, a correlation was established between the extent and location of the regional perfusion deficiencies (studied by scintigraphy) and overall functional disturbances Vmax MEVS X 100VC, residual volume, R, PaO2, PaCO2). In 85% of the cases regional perfusion disturbances were detected and grouped into six scintigraphic types. A good correlation was found between these disturbances and the MEVS X 100/VC index and modified partial pressure of the gases (O2, CO2) in the arterial blood. Unexpected was the absence of a mathematical correlation between perfusion disturbances and the residual volume and R, suggesting the great variety of the disturbances grouped under the general denomination of chronic obstructive bronchopneumopathy.", "contents": "[Contribution of pulmonary scintiscanning to the diagnosis of chronic obstructive bronchopneumopathy]. In a lot of 32 cases of chronic obstructive bronchopneumopathy, a correlation was established between the extent and location of the regional perfusion deficiencies (studied by scintigraphy) and overall functional disturbances Vmax MEVS X 100VC, residual volume, R, PaO2, PaCO2). In 85% of the cases regional perfusion disturbances were detected and grouped into six scintigraphic types. A good correlation was found between these disturbances and the MEVS X 100/VC index and modified partial pressure of the gases (O2, CO2) in the arterial blood. Unexpected was the absence of a mathematical correlation between perfusion disturbances and the residual volume and R, suggesting the great variety of the disturbances grouped under the general denomination of chronic obstructive bronchopneumopathy."}
{"id": "PMID:188116", "title": "Exclusion of pre-beta lipoproteins from agarose gel electrophoresis in the presence of chylomicrons.", "content": "Chylomicrons present in the fasting serum of patients with type V hyperlipoproteinaemia have been found to exclude pre-beta lipoproteins from entering into agarose gel during lipoprotein electrophoresis. It is recommended that when chylomicrons are present they be removed prior to diagnostic and quantitative lipoprotein electrophoresis in agarose gel.", "contents": "Exclusion of pre-beta lipoproteins from agarose gel electrophoresis in the presence of chylomicrons. Chylomicrons present in the fasting serum of patients with type V hyperlipoproteinaemia have been found to exclude pre-beta lipoproteins from entering into agarose gel during lipoprotein electrophoresis. It is recommended that when chylomicrons are present they be removed prior to diagnostic and quantitative lipoprotein electrophoresis in agarose gel."}
{"id": "PMID:188111", "title": "[Results of intermittent treatment with antitubercular agents in cavernous pulmonary tuberculosis in adults].", "content": "The effectiveness of the intermittent treatment (2/7) with Rifampicin + Etambutol, administered over periods of 3 to 24 months, was tested in a log of 229 out-patients suffering from tuberculosis (bacilli carriers). Negativation of the cultures was obtained in 88.4% of the cases, most of the failures being recorded in the aged patients from rural areas, suffering from various other associated diseases and in those who did not cooperate. As these patients raise particular problems concerning the therapeutical attitude, the authors consider they should be admitted to hospital, at least during the critical periods of the disease.", "contents": "[Results of intermittent treatment with antitubercular agents in cavernous pulmonary tuberculosis in adults]. The effectiveness of the intermittent treatment (2/7) with Rifampicin + Etambutol, administered over periods of 3 to 24 months, was tested in a log of 229 out-patients suffering from tuberculosis (bacilli carriers). Negativation of the cultures was obtained in 88.4% of the cases, most of the failures being recorded in the aged patients from rural areas, suffering from various other associated diseases and in those who did not cooperate. As these patients raise particular problems concerning the therapeutical attitude, the authors consider they should be admitted to hospital, at least during the critical periods of the disease."}
{"id": "PMID:188112", "title": "[Influence of tobacco smoking on the development of experimental pulmonary tuberculosis].", "content": "The present investigation was designed to the study, in rabbits, of morphologic and enzymatic pulmonary alterations produced by tobacco smoke and the course of tuberculosis under these conditions. The histologic examination revealed muciparous hyperplasia and pavementing metaplasia of the bronchic epithelium, accompanied by interstitial cellular reactions, reticulin, fibrilogenesis, atelectasis, emphysema and marked debility of the animals. In the animals treated with tobacco smoke the tuberculous lesions were very extensive and had an exudative-necrotic character. Under the influence of chemotherapy, applied during three months, reorganization of the lesions was reduced in comparison to the controls and an intense bacteriological activity persisted.", "contents": "[Influence of tobacco smoking on the development of experimental pulmonary tuberculosis]. The present investigation was designed to the study, in rabbits, of morphologic and enzymatic pulmonary alterations produced by tobacco smoke and the course of tuberculosis under these conditions. The histologic examination revealed muciparous hyperplasia and pavementing metaplasia of the bronchic epithelium, accompanied by interstitial cellular reactions, reticulin, fibrilogenesis, atelectasis, emphysema and marked debility of the animals. In the animals treated with tobacco smoke the tuberculous lesions were very extensive and had an exudative-necrotic character. Under the influence of chemotherapy, applied during three months, reorganization of the lesions was reduced in comparison to the controls and an intense bacteriological activity persisted."}
{"id": "PMID:188117", "title": "Virus-specific IgM antibodies in acute gastroenteritis due to a reovirus-like agent (rotavirus).", "content": "62 serum samples from 24 patients with rotavirus gastroenteritis were tested for IgM antibodies against a bovine rotavirus by an indirect fluorescent antibody technique. IgM antibodies were detected in one or more of the serum samples from all but one of the patients. IgM antibodies were not detected in samples obtained from 11 of the patients after the 5th week of illness. Absorption of sera for IgG with Staphylococcus aureus increased the sensitivity of the IgM antibody test. It is concluded that the presence of IgM antibodies against bovine rotavirus in a patient's serum, as measured by the present technique, does suggest a recent rotavirus infection. On the other hand, the lack of IgM antibodies in the serum of a child with acute gastroenteritis between the second and the 5th week of illness tends to exclude rotavirus as a cause of the disease.", "contents": "Virus-specific IgM antibodies in acute gastroenteritis due to a reovirus-like agent (rotavirus). 62 serum samples from 24 patients with rotavirus gastroenteritis were tested for IgM antibodies against a bovine rotavirus by an indirect fluorescent antibody technique. IgM antibodies were detected in one or more of the serum samples from all but one of the patients. IgM antibodies were not detected in samples obtained from 11 of the patients after the 5th week of illness. Absorption of sera for IgG with Staphylococcus aureus increased the sensitivity of the IgM antibody test. It is concluded that the presence of IgM antibodies against bovine rotavirus in a patient's serum, as measured by the present technique, does suggest a recent rotavirus infection. On the other hand, the lack of IgM antibodies in the serum of a child with acute gastroenteritis between the second and the 5th week of illness tends to exclude rotavirus as a cause of the disease."}
{"id": "PMID:188113", "title": "[Clinical observations on 2 cases of congenital pulmonary malformation].", "content": "The present paper reports on two cases of congenital malformation of the lungs, in young adults, treated surgically. Each case had particular clinical features: left pulmonary aplasia with residual thymus and herniation of the right lung in the left pleural cavity in one case, and left pulmonary hypoplasia with aberrant pulmonary circulation, secondary cystic bronchiectasia, serofibrinous pleurisy. The necessity of an early diagnosis and surgical treatment is emphasized.", "contents": "[Clinical observations on 2 cases of congenital pulmonary malformation]. The present paper reports on two cases of congenital malformation of the lungs, in young adults, treated surgically. Each case had particular clinical features: left pulmonary aplasia with residual thymus and herniation of the right lung in the left pleural cavity in one case, and left pulmonary hypoplasia with aberrant pulmonary circulation, secondary cystic bronchiectasia, serofibrinous pleurisy. The necessity of an early diagnosis and surgical treatment is emphasized."}
{"id": "PMID:188118", "title": "The clinical features of infantile gastroenteritis due to rotavirus.", "content": "The symptoms of 100 hospitalised cases of rotavirus infantile gastroenteritis are described. Most patients presented with high fever between the 2nd and 5th day, having started with diarrhoea or vomiting or both. 42% of the infants had upper respiratory tract symptoms. Severe electrolyte disturbance did not occur, although there was a suggestion of a correlation between the higher blood ureas and the number of rotavirus particles in the stools. The mean duration of illness of uncomplicated cases was 13.4 days. Infants were more severely affected when enteropathic coliforms were also present, the total duration of illness being extended to 23 days. It is suggested that rotavirus or similar virus infection may be an essential precursor in the majority of coliform gastroenteritis.", "contents": "The clinical features of infantile gastroenteritis due to rotavirus. The symptoms of 100 hospitalised cases of rotavirus infantile gastroenteritis are described. Most patients presented with high fever between the 2nd and 5th day, having started with diarrhoea or vomiting or both. 42% of the infants had upper respiratory tract symptoms. Severe electrolyte disturbance did not occur, although there was a suggestion of a correlation between the higher blood ureas and the number of rotavirus particles in the stools. The mean duration of illness of uncomplicated cases was 13.4 days. Infants were more severely affected when enteropathic coliforms were also present, the total duration of illness being extended to 23 days. It is suggested that rotavirus or similar virus infection may be an essential precursor in the majority of coliform gastroenteritis."}
{"id": "PMID:188119", "title": "Rotavirus-associated gastroenteritis in two adults probably caused by virus reinfection.", "content": "Rotavirus infection was diagnosed by virus detection and by serological methods in 2 women with acute gastroenteritis, aged 22 and 29 years, respectively. Both patients had been in close contact with children with rotavirus gastroenteritis. Rotavirus-specific antibodies were detected in serum specimens obtained prior to the illness in one of the patients, and the serological response in both patients suggested a reinfection with rotavirus as cause of the disease.", "contents": "Rotavirus-associated gastroenteritis in two adults probably caused by virus reinfection. Rotavirus infection was diagnosed by virus detection and by serological methods in 2 women with acute gastroenteritis, aged 22 and 29 years, respectively. Both patients had been in close contact with children with rotavirus gastroenteritis. Rotavirus-specific antibodies were detected in serum specimens obtained prior to the illness in one of the patients, and the serological response in both patients suggested a reinfection with rotavirus as cause of the disease."}
{"id": "PMID:188120", "title": "[Ganglions a rare cause of isolated peripheral nerve lesions].", "content": "Extra- and intraneural ganglionic cysts rarely involved peripheral nerves. They are found in the neighbourhood of large joints. The ulnar nerve is affected most often by extraneural cysts at the wrist. Intraneural cysts prefer the peroneal nerve at the tibiofibular joint. Ganglionic cysts as a cause of peripheral nerve damage are often overlooked, mainly because they are not considered as a cause of pain, paresis or sensory changes. Surgical treatment is recommended.", "contents": "[Ganglions a rare cause of isolated peripheral nerve lesions]. Extra- and intraneural ganglionic cysts rarely involved peripheral nerves. They are found in the neighbourhood of large joints. The ulnar nerve is affected most often by extraneural cysts at the wrist. Intraneural cysts prefer the peroneal nerve at the tibiofibular joint. Ganglionic cysts as a cause of peripheral nerve damage are often overlooked, mainly because they are not considered as a cause of pain, paresis or sensory changes. Surgical treatment is recommended."}
{"id": "PMID:188121", "title": "[How do hormones act?].", "content": "Hormones act via receptors, i.e. structures which contain specific binding sites for any given hormone. The transmission of information is accomplished by reversible binding of the hormone to the receptor. Steroid hormones and triiodothyronine act via receptors which are located in the nucleus and regulate the biosynthesis of specific proteins. Peptide hormones and catecholamines combine with receptors within the cell membrane, thereby regulating the membrane-bound enzyme adenyle cyclase. The product of this enzyme, cyclic AMP, acts as a transmitter of the action of these hormones in the interior of the cell.", "contents": "[How do hormones act?]. Hormones act via receptors, i.e. structures which contain specific binding sites for any given hormone. The transmission of information is accomplished by reversible binding of the hormone to the receptor. Steroid hormones and triiodothyronine act via receptors which are located in the nucleus and regulate the biosynthesis of specific proteins. Peptide hormones and catecholamines combine with receptors within the cell membrane, thereby regulating the membrane-bound enzyme adenyle cyclase. The product of this enzyme, cyclic AMP, acts as a transmitter of the action of these hormones in the interior of the cell."}
{"id": "PMID:188122", "title": "[Radioimmunological measurement methods in ambulatory endocrinology].", "content": "Measurements of plasma-hormone concentrations can be helpful for differential diagnosis in clinically suspect endocrine disorders. By means of radioimmunological methods a series of hormones can be estimated in small plasma volumes. The assay technique differs from chemical methods routinely used in a clinical laboratory. Reagents and details of immunoassay procedures vary between laboratories, and hence hormone estimations from different institutes cannot be directly compared. The plasma half-life of many hormones is 10-30 minutes. The regulation of hormone secretion is complex. Dynamic tests using a known stimulation or suppression provide a better estimate of the function of an endocrine axis than a single random measurement. Hormone assays should be required and interpreted in close collaboration with the endocrine laboratory, which should provide competent counseling with respect to methodologic and endocrinologic aspects.", "contents": "[Radioimmunological measurement methods in ambulatory endocrinology]. Measurements of plasma-hormone concentrations can be helpful for differential diagnosis in clinically suspect endocrine disorders. By means of radioimmunological methods a series of hormones can be estimated in small plasma volumes. The assay technique differs from chemical methods routinely used in a clinical laboratory. Reagents and details of immunoassay procedures vary between laboratories, and hence hormone estimations from different institutes cannot be directly compared. The plasma half-life of many hormones is 10-30 minutes. The regulation of hormone secretion is complex. Dynamic tests using a known stimulation or suppression provide a better estimate of the function of an endocrine axis than a single random measurement. Hormone assays should be required and interpreted in close collaboration with the endocrine laboratory, which should provide competent counseling with respect to methodologic and endocrinologic aspects."}
{"id": "PMID:188123", "title": "[Adrenocortical diagnosis in ambulatory practice].", "content": "The determination of plasma cortisol concentrations is a valuable aid in the diagnosis of some important adrenocortical diseases. Since cortisol is secreted episodically, the diagnostic value of diurnal profiles of plasma cortisol is often limited. On the other hand, a simple ACTH test or an overnight dexamethasone suppression test permit, in most instances, definite diagnosis or exclusion of adrenocortical insufficiency and Cushing's syndrome respectively.", "contents": "[Adrenocortical diagnosis in ambulatory practice]. The determination of plasma cortisol concentrations is a valuable aid in the diagnosis of some important adrenocortical diseases. Since cortisol is secreted episodically, the diagnostic value of diurnal profiles of plasma cortisol is often limited. On the other hand, a simple ACTH test or an overnight dexamethasone suppression test permit, in most instances, definite diagnosis or exclusion of adrenocortical insufficiency and Cushing's syndrome respectively."}
{"id": "PMID:188124", "title": "[Changes in serum lipids and lipoproteins in acute hepatitis].", "content": "In 50 patients with acute hepatitis serum lipide and lipoproteins were determined at regular intervals and the results were compared with the usual liver function tests. Australia-antigen was established in 26 patients. During the first three weeks of the disease the most striking finding was a significant increase in the triglycerides, which was most pronounced at the end of the second week. Triglyceride levels usually returned to normal during the fourth week. In the course of the disease, lipoprotein electrophoresis showed marked decrease or absence of alpha- and pre-beta-lipoproteins during the first two weeks. During the third week faint alpha and pre-beta bands recurred in most patients. By the end of the fourth week lipoprotein electrophoretic findings were back to normal. There was general correlation between routine tests of liver function and results of lipid analyses throughout the course of the disease. This typical pattern of serum lipid and lipoprotein changes was found with near-consistency in patients with HAA-positive hepatitis. It was also present in the majority of HAA-negative patients, though in these the characteristic discrepancy between hypertriglyceridemia and simultaneous decrease of the pre-beta-lipoprotein band in eletrophoresis was, on the average, absent.", "contents": "[Changes in serum lipids and lipoproteins in acute hepatitis]. In 50 patients with acute hepatitis serum lipide and lipoproteins were determined at regular intervals and the results were compared with the usual liver function tests. Australia-antigen was established in 26 patients. During the first three weeks of the disease the most striking finding was a significant increase in the triglycerides, which was most pronounced at the end of the second week. Triglyceride levels usually returned to normal during the fourth week. In the course of the disease, lipoprotein electrophoresis showed marked decrease or absence of alpha- and pre-beta-lipoproteins during the first two weeks. During the third week faint alpha and pre-beta bands recurred in most patients. By the end of the fourth week lipoprotein electrophoretic findings were back to normal. There was general correlation between routine tests of liver function and results of lipid analyses throughout the course of the disease. This typical pattern of serum lipid and lipoprotein changes was found with near-consistency in patients with HAA-positive hepatitis. It was also present in the majority of HAA-negative patients, though in these the characteristic discrepancy between hypertriglyceridemia and simultaneous decrease of the pre-beta-lipoprotein band in eletrophoresis was, on the average, absent."}
{"id": "PMID:188128", "title": "High-field 13C NMR Studies of certain normal and abnormal human plasma lipoproteins.", "content": "High-field (63.4 kilogauss) Fourier transform nuclear magnetic resonance spectroscopy 13C in natural abundance has been used to study the structural organization and molecular dynamics of constituent lipids of normal human very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The same method was used to study the abnormal beta-VLDL of two type III hyperlipoproteinemia patients having markedly differing ratios of VLDL cholesterol to triglyceride (0.3 and 0.6, respectively). Resolution obtained at 63.4 kilogauss has made possible the assignment of several additional resonances of cholesterol ring carbon atoms, not resolved in earlier studies at lower fields, in the VLDL spectra. The rotational reorientation of the ring portion of cholesteryl esters in VLDL (normal) and beta-VLDL (abnormal) is not highly anisotropic and is similar to that for cholesteryl esters disolved in excess triolein. The rotations of cholesteryl esters in LDL are more highly anisotropic and significantly more restricted. The results suggest that the structural organization of the lipid components in beta-VLDL resembles that found in normal VLDL but differs significantly from that for normal LDL.", "contents": "High-field 13C NMR Studies of certain normal and abnormal human plasma lipoproteins. High-field (63.4 kilogauss) Fourier transform nuclear magnetic resonance spectroscopy 13C in natural abundance has been used to study the structural organization and molecular dynamics of constituent lipids of normal human very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The same method was used to study the abnormal beta-VLDL of two type III hyperlipoproteinemia patients having markedly differing ratios of VLDL cholesterol to triglyceride (0.3 and 0.6, respectively). Resolution obtained at 63.4 kilogauss has made possible the assignment of several additional resonances of cholesterol ring carbon atoms, not resolved in earlier studies at lower fields, in the VLDL spectra. The rotational reorientation of the ring portion of cholesteryl esters in VLDL (normal) and beta-VLDL (abnormal) is not highly anisotropic and is similar to that for cholesteryl esters disolved in excess triolein. The rotations of cholesteryl esters in LDL are more highly anisotropic and significantly more restricted. The results suggest that the structural organization of the lipid components in beta-VLDL resembles that found in normal VLDL but differs significantly from that for normal LDL."}
{"id": "PMID:188129", "title": "Bovine lymphosarcoma: development of a radioimmunologic technique for detection of the etiologic agent.", "content": "A highly sensitive and specific radioimmunoassay has been developed for the major structural protein of an oncornavirus etiologically associated with bovine lymphosarcoma. This test can be used to identify cattle which have been exposed to the bovine leukemia virus and may thus develop or transmit the disease. Analysis of randomly obtained serums indicates that infection that infection with this virus is widespread among cattle.", "contents": "Bovine lymphosarcoma: development of a radioimmunologic technique for detection of the etiologic agent. A highly sensitive and specific radioimmunoassay has been developed for the major structural protein of an oncornavirus etiologically associated with bovine lymphosarcoma. This test can be used to identify cattle which have been exposed to the bovine leukemia virus and may thus develop or transmit the disease. Analysis of randomly obtained serums indicates that infection that infection with this virus is widespread among cattle."}
{"id": "PMID:188130", "title": "Hormonal release of programmed behavior in silk moths: probable mediation by cyclic AMP.", "content": "The eclosion hormone triggers a stereotyped preprogrammed pattern of behavior in silk moths. The effects of the hormone were duplicated by the injection of dibutyryl adenosine 3', 5'-monophosphate, adenosine 3', 5'-monophosphate (cyclic AMP), or guanosine 3', 5'-monophosphate (cyclic GMP) into theophylline-treated pharate moths. Treatment with theophylline reduced the latency of the response to a low dose of hormone, presumably by blocking phosphodiesterase. Endogenous levels of cyclic AMP, but not cyclic GMP, increased significantly in the central nervous system within 10 minutes after hormone injection. We conclude that an early step leading to the release of the eclosion motor program is an increase in cyclic AMP in target neurons of the central nervous system.", "contents": "Hormonal release of programmed behavior in silk moths: probable mediation by cyclic AMP. The eclosion hormone triggers a stereotyped preprogrammed pattern of behavior in silk moths. The effects of the hormone were duplicated by the injection of dibutyryl adenosine 3', 5'-monophosphate, adenosine 3', 5'-monophosphate (cyclic AMP), or guanosine 3', 5'-monophosphate (cyclic GMP) into theophylline-treated pharate moths. Treatment with theophylline reduced the latency of the response to a low dose of hormone, presumably by blocking phosphodiesterase. Endogenous levels of cyclic AMP, but not cyclic GMP, increased significantly in the central nervous system within 10 minutes after hormone injection. We conclude that an early step leading to the release of the eclosion motor program is an increase in cyclic AMP in target neurons of the central nervous system."}
{"id": "PMID:188131", "title": "Synaptic transmission: long-lasting potentiation by a postsynaptic mechanism.", "content": "Slow decreases of ionic conductance across neuronal cell membranes, which generate slow synaptic potentials, can increase the effectiveness of synaptic transmission. Slow conductance decreases sufficient magnitude increase the amplitude of monosynaptic fast excitatory postsynaptic potentials in B cells of the bullfrog sympathetic ganglion. By this postsynaptic mechanism, activation of one synaptic pathway can cause an increase in transmission, lasting several minutes, across another synapse. This may provide an important mechanism for synaptic integration and control of neuronal interaction.", "contents": "Synaptic transmission: long-lasting potentiation by a postsynaptic mechanism. Slow decreases of ionic conductance across neuronal cell membranes, which generate slow synaptic potentials, can increase the effectiveness of synaptic transmission. Slow conductance decreases sufficient magnitude increase the amplitude of monosynaptic fast excitatory postsynaptic potentials in B cells of the bullfrog sympathetic ganglion. By this postsynaptic mechanism, activation of one synaptic pathway can cause an increase in transmission, lasting several minutes, across another synapse. This may provide an important mechanism for synaptic integration and control of neuronal interaction."}
{"id": "PMID:188132", "title": "Analysis of living tissue by phosphorus-31 magnetic resonance.", "content": "Nuclear magnetic resonance is a new method for assaying the content of phosphate metabolites in intact tissues. Its nondestructive nature allows simultaneous and repeated determinations of these compounds with a minimum perturbation of tissue. Changes in the concentrations of the phosphates as a function of time characterize the metabolic machinery of the tissue and reveal alterations in enzymic activity that result from drug treatment or disease. The entire phosphate profile shows differences between normal and diseased muscle which should be of diagnostic value. Further, by examining phosphate profiles we detected a family of chemical compounds that were not previously known to exist as major constituents in muscle. Of these, two have been isolated and one has been identified as glycerol 3-phosphorylcholine. Finally, shifts in the positions of resonances monitor the internal environment of the living system, its hydrogen ion concentration, the complexing of alkaline earth metals with ATP, and compartmentalization within the cell.", "contents": "Analysis of living tissue by phosphorus-31 magnetic resonance. Nuclear magnetic resonance is a new method for assaying the content of phosphate metabolites in intact tissues. Its nondestructive nature allows simultaneous and repeated determinations of these compounds with a minimum perturbation of tissue. Changes in the concentrations of the phosphates as a function of time characterize the metabolic machinery of the tissue and reveal alterations in enzymic activity that result from drug treatment or disease. The entire phosphate profile shows differences between normal and diseased muscle which should be of diagnostic value. Further, by examining phosphate profiles we detected a family of chemical compounds that were not previously known to exist as major constituents in muscle. Of these, two have been isolated and one has been identified as glycerol 3-phosphorylcholine. Finally, shifts in the positions of resonances monitor the internal environment of the living system, its hydrogen ion concentration, the complexing of alkaline earth metals with ATP, and compartmentalization within the cell."}
{"id": "PMID:188133", "title": "Slow persistent infection caused by visna virus: role of host restriction.", "content": "Proviral DNA has been demonstrated by in situ hybridization in foci of cells of a lamb infected with the RNA slow virus visna. A few of these cells also contain the major virion structural antigen p30. This restriction in virus gene expression in the infected animal provides a mechanism for persistence of virus in this chronic infection.", "contents": "Slow persistent infection caused by visna virus: role of host restriction. Proviral DNA has been demonstrated by in situ hybridization in foci of cells of a lamb infected with the RNA slow virus visna. A few of these cells also contain the major virion structural antigen p30. This restriction in virus gene expression in the infected animal provides a mechanism for persistence of virus in this chronic infection."}
{"id": "PMID:188134", "title": "Collagenase production by rheumatoid synovial cells: stimulation by a human lymphocyte factor.", "content": "Human peripheral blood lymphocytes incubated in culture for 1 to 3 days at 37 degree C, but not at 4 degree C, release a soluble factor which can stimulate, up to 400-fold, collagenase production by isolated, adherent, rheumatoid synovial cells. Production of lymphocyte factor is enhanced by phytohemagglutinin or concanavalin A. By gel filtration the factor has an apparent molecular weight of about 12,000.", "contents": "Collagenase production by rheumatoid synovial cells: stimulation by a human lymphocyte factor. Human peripheral blood lymphocytes incubated in culture for 1 to 3 days at 37 degree C, but not at 4 degree C, release a soluble factor which can stimulate, up to 400-fold, collagenase production by isolated, adherent, rheumatoid synovial cells. Production of lymphocyte factor is enhanced by phytohemagglutinin or concanavalin A. By gel filtration the factor has an apparent molecular weight of about 12,000."}
{"id": "PMID:188135", "title": "Localization of cyclic GMP and cyclic AMP in cardiac and skeletal muscle: immunocytochemical demonstration.", "content": "When rat cardiac and skeletal muscle are explored by immunocytochemical procedures designed to show sites of localization of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP), distinct staining patterns for the two nucleotides are seen. Antibody to cyclic AMP is found in the area of the sarcoplasmic reticulum, while antibody to cyclic GMP is found with a periodic distribution corresponding to that of the A band. This suggests a role for cyclic GMP in the regulation of myosin.", "contents": "Localization of cyclic GMP and cyclic AMP in cardiac and skeletal muscle: immunocytochemical demonstration. When rat cardiac and skeletal muscle are explored by immunocytochemical procedures designed to show sites of localization of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP), distinct staining patterns for the two nucleotides are seen. Antibody to cyclic AMP is found in the area of the sarcoplasmic reticulum, while antibody to cyclic GMP is found with a periodic distribution corresponding to that of the A band. This suggests a role for cyclic GMP in the regulation of myosin."}
{"id": "PMID:188136", "title": "Glia maturation factor: effect on chemical differentiation of glioblasts in culture.", "content": "A protein factor from the adult brain increases the concentrations of adenosine 3',5'-monophosphate and S-100 protein in glioblasts in culture. Such changes are correlated with the outgrowth of cell processes.", "contents": "Glia maturation factor: effect on chemical differentiation of glioblasts in culture. A protein factor from the adult brain increases the concentrations of adenosine 3',5'-monophosphate and S-100 protein in glioblasts in culture. Such changes are correlated with the outgrowth of cell processes."}
{"id": "PMID:188137", "title": "Defined dimensional changes in enzyme cofactors: fluorescent \"stretched-out\" analogs of adenine nucleotides.", "content": "A concept is presented for testing the dimensional restrictions of enzyme-active sites by stretching the substrate or cofactor by known magnitude. These restrictions of enzyme-active sites specific for purine cofactors were tested by the synthesis and evaluation of lin-benzoadenosine 5'-triphosphate, 5'-diphosphate, and 3',5'-monophosphate with respect to enzyme binding and activity. These \"stretchedout\" (by 2.4 angstroms) versions of the adenine ribonucleotides bind strongly, slow the enzymatic rates, and have useful fluorescence properties.", "contents": "Defined dimensional changes in enzyme cofactors: fluorescent \"stretched-out\" analogs of adenine nucleotides. A concept is presented for testing the dimensional restrictions of enzyme-active sites by stretching the substrate or cofactor by known magnitude. These restrictions of enzyme-active sites specific for purine cofactors were tested by the synthesis and evaluation of lin-benzoadenosine 5'-triphosphate, 5'-diphosphate, and 3',5'-monophosphate with respect to enzyme binding and activity. These \"stretchedout\" (by 2.4 angstroms) versions of the adenine ribonucleotides bind strongly, slow the enzymatic rates, and have useful fluorescence properties."}
{"id": "PMID:188138", "title": "Endogenous opiate receptor ligand: electrically induced release in the guinea pig ileum.", "content": "Opiate receptors mediate the electrically evoked inhibition of the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum. The electrically induced activation of the opiate receptor was produced by a prolonged simulation at 10 hertz and provides the first evidence that an endogenous opiate receptor ligand is released by nerve stimulation. The specificity of the phenomenon was demonstrated by the reversal obtained with the narcotic antagonists naloxone, naltrexone, and GPA 1843; GPA 1847, the (+)-isomer of 1843, did not cause reversal. The model system described should be useful for the study of the storage, synthesis, and release of endorphins.", "contents": "Endogenous opiate receptor ligand: electrically induced release in the guinea pig ileum. Opiate receptors mediate the electrically evoked inhibition of the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum. The electrically induced activation of the opiate receptor was produced by a prolonged simulation at 10 hertz and provides the first evidence that an endogenous opiate receptor ligand is released by nerve stimulation. The specificity of the phenomenon was demonstrated by the reversal obtained with the narcotic antagonists naloxone, naltrexone, and GPA 1843; GPA 1847, the (+)-isomer of 1843, did not cause reversal. The model system described should be useful for the study of the storage, synthesis, and release of endorphins."}
{"id": "PMID:188139", "title": "[Bronchial biopsy and fiberscopy].", "content": "The authors report the results of bronchial biopsies carried out during fiber endoscopy in 165 patients, including 100 bronchial carcinomas, 17 cases of tuberculosis, 7 cases of sarcoidosis, and 41 patients with various forms of respiratory disease, out of a total of nearly 900 fiber endoscopies carried out directly under local anesthesia.  It appears that the tissue samples obtained by biopsy with forceps are interpretable in almost all cases, that the result of biopsy is nil in sarcoidosis, low or limited, in cases of granuloma budding into the bronchial lumen as in tuberculosis.  In bronchial carcinoma, the proof of malignancy was made in 65% of cases and the histological type determined in 52% of cases. These levels rose respectively to 75.7 and 62.2% in cases where the endoscopic appearance was that of a bud of vegetation.  These results make this method competitive in bronchial carcinoma, compared with other methods of sampling, biopsy carried out under bronchoscopy and bronchial brushing under fiber endoscopy in particular.", "contents": "[Bronchial biopsy and fiberscopy]. The authors report the results of bronchial biopsies carried out during fiber endoscopy in 165 patients, including 100 bronchial carcinomas, 17 cases of tuberculosis, 7 cases of sarcoidosis, and 41 patients with various forms of respiratory disease, out of a total of nearly 900 fiber endoscopies carried out directly under local anesthesia.  It appears that the tissue samples obtained by biopsy with forceps are interpretable in almost all cases, that the result of biopsy is nil in sarcoidosis, low or limited, in cases of granuloma budding into the bronchial lumen as in tuberculosis.  In bronchial carcinoma, the proof of malignancy was made in 65% of cases and the histological type determined in 52% of cases. These levels rose respectively to 75.7 and 62.2% in cases where the endoscopic appearance was that of a bud of vegetation.  These results make this method competitive in bronchial carcinoma, compared with other methods of sampling, biopsy carried out under bronchoscopy and bronchial brushing under fiber endoscopy in particular."}
{"id": "PMID:188140", "title": "[Richettsial pericarditis and pleurisy].", "content": "The authors report two cases of rickettsial disease due to R. Conori with mainly pericarditis in one case, sero-fibrinous pleurisy in the other.  They then recall a few general data concerning this rickettsial disease and the very restricted place that it occupies in the etiology of pericarditis and, even more so, in the case of pleurisy.  The conditons of diagnosis, which are mainly serological, are discussed, in particular with regard to pericarditis and tuberculous pleurisy.", "contents": "[Richettsial pericarditis and pleurisy]. The authors report two cases of rickettsial disease due to R. Conori with mainly pericarditis in one case, sero-fibrinous pleurisy in the other.  They then recall a few general data concerning this rickettsial disease and the very restricted place that it occupies in the etiology of pericarditis and, even more so, in the case of pleurisy.  The conditons of diagnosis, which are mainly serological, are discussed, in particular with regard to pericarditis and tuberculous pleurisy."}
{"id": "PMID:188141", "title": "[Hepatic schistosomiasis and sarcoidosis with voluminous subdiaphragmatic adenopathies].", "content": "The authors report a case of a West-Indian with sarcoidosis and peripheral, mediastinal and, above all, sub-diaphragmatic lymph nodes. The latter were very large and palpable through the abdomen, confirmed by lymphography and found to be due to S. Mansomi schistosomiasis. Liver biopsy carried out under peritoneoscopy, showed schistosomal granulomatosis with sarcoidosic granulomatosis. The authors consider that the rareness of this association is only apparent and does not correspond to the frequency of bilharziasis nor that of sarcoidosis in these subjects. They emphasize the mistakes which may result in interpretation of liver biopsy. They recall a few special characteristics of sarcoidosis in West-Indians, in particular, the possibility of failure of corticosteroid therapy as in their case, due to the onset of miliary lung disease under treatment, and show the lymphographic appearances of sarcoidosis.", "contents": "[Hepatic schistosomiasis and sarcoidosis with voluminous subdiaphragmatic adenopathies]. The authors report a case of a West-Indian with sarcoidosis and peripheral, mediastinal and, above all, sub-diaphragmatic lymph nodes. The latter were very large and palpable through the abdomen, confirmed by lymphography and found to be due to S. Mansomi schistosomiasis. Liver biopsy carried out under peritoneoscopy, showed schistosomal granulomatosis with sarcoidosic granulomatosis. The authors consider that the rareness of this association is only apparent and does not correspond to the frequency of bilharziasis nor that of sarcoidosis in these subjects. They emphasize the mistakes which may result in interpretation of liver biopsy. They recall a few special characteristics of sarcoidosis in West-Indians, in particular, the possibility of failure of corticosteroid therapy as in their case, due to the onset of miliary lung disease under treatment, and show the lymphographic appearances of sarcoidosis."}
{"id": "PMID:188146", "title": "[Australia antigen and chronic hepatitis in blood donors].", "content": "A routine search for Australia antigen in 29,936 blood donors at the Orleans Hospital Blood Transfusion centre led to the discovery of 105 apparently healthy carriers. Liver function tests were carried out in 80 of the latter and revealed abnormalities in 34 of them. Out of 18 patients who had no other explanation such as alcohol or drugs and who had abnormal tests six months later, 11 accepted liver biopsy. Histology revealed 4 cases of post-hepatic cirrhosis, 2 cases of chronic aggressive hepatitis, 2 cases of chronic persistent hepatitis and 3 livers with non-specific changes.", "contents": "[Australia antigen and chronic hepatitis in blood donors]. A routine search for Australia antigen in 29,936 blood donors at the Orleans Hospital Blood Transfusion centre led to the discovery of 105 apparently healthy carriers. Liver function tests were carried out in 80 of the latter and revealed abnormalities in 34 of them. Out of 18 patients who had no other explanation such as alcohol or drugs and who had abnormal tests six months later, 11 accepted liver biopsy. Histology revealed 4 cases of post-hepatic cirrhosis, 2 cases of chronic aggressive hepatitis, 2 cases of chronic persistent hepatitis and 3 livers with non-specific changes."}
{"id": "PMID:188147", "title": "[Clinical and statistical study of 100 patients with vitiligo. II. Associated lesions].", "content": "A study of 100 cases of vitiligo showed the frequency of associated skin and visceral lesions. A skin disease was associated in 24 cases: psoriasis 4 cases, alopecia 4 cases, eczema 3 cases, malignant melanoma 2 cases, dermatitis herpetiformis 1 case, lichen planus 9 cases. However, only one case of Sutton's naevus was noted. Among other associations noted in 28 cases, there were 7 cases of thyroid disease, 5 cases of diabetes, 1 case of chronic rheumatoid arthritis and 3 gastric disorders. The frequency of these various associations was discussed in the light of other authors' reports. If one compares the 21 cases associated with auto-immune disease and the other cases of vitiligo, there was no significant difference for the various parameters studied. Thus the significance of the various biological signs of autoimmunisation remains doubtful and even the precise definition of vitiligo remains uncertain.", "contents": "[Clinical and statistical study of 100 patients with vitiligo. II. Associated lesions]. A study of 100 cases of vitiligo showed the frequency of associated skin and visceral lesions. A skin disease was associated in 24 cases: psoriasis 4 cases, alopecia 4 cases, eczema 3 cases, malignant melanoma 2 cases, dermatitis herpetiformis 1 case, lichen planus 9 cases. However, only one case of Sutton's naevus was noted. Among other associations noted in 28 cases, there were 7 cases of thyroid disease, 5 cases of diabetes, 1 case of chronic rheumatoid arthritis and 3 gastric disorders. The frequency of these various associations was discussed in the light of other authors' reports. If one compares the 21 cases associated with auto-immune disease and the other cases of vitiligo, there was no significant difference for the various parameters studied. Thus the significance of the various biological signs of autoimmunisation remains doubtful and even the precise definition of vitiligo remains uncertain."}
{"id": "PMID:188148", "title": "[Meningoradiculitis after tick bites. Apropos of 9 cases].", "content": "The authors report a series of 9 cases of meningoradiculitis after tick bites and compare them with 56 other cases in the literature. Clinically, the bite is followed by a free interval, then more or less extensive local erythema, pain then paralysis is undoubtedly the most typical presentation. Uni- or bilateral paralysis of the 7th cranial nerve was found in more than 50% of cases. Erythema may exceptionally be absent. There may be forms with pain alone. Finally, there may sometimes be pyramidal signs or signs of brain irritation. As concerns the course, one should note the absence of respiratory complications, and although there are usually no or minimal sequelae, one should note the slowness of the recovery in certain paralytic cases. In the laboratory, pleocytosis is constantly found in the C.S.F. As concerns physiopathology, there are 3 theories, virus, allergic and toxic.", "contents": "[Meningoradiculitis after tick bites. Apropos of 9 cases]. The authors report a series of 9 cases of meningoradiculitis after tick bites and compare them with 56 other cases in the literature. Clinically, the bite is followed by a free interval, then more or less extensive local erythema, pain then paralysis is undoubtedly the most typical presentation. Uni- or bilateral paralysis of the 7th cranial nerve was found in more than 50% of cases. Erythema may exceptionally be absent. There may be forms with pain alone. Finally, there may sometimes be pyramidal signs or signs of brain irritation. As concerns the course, one should note the absence of respiratory complications, and although there are usually no or minimal sequelae, one should note the slowness of the recovery in certain paralytic cases. In the laboratory, pleocytosis is constantly found in the C.S.F. As concerns physiopathology, there are 3 theories, virus, allergic and toxic."}
{"id": "PMID:188149", "title": "[Changes in bone marrow cellularity close to cancer metastases. Cyto-histologic study].", "content": "Before starting any therapy, we systematically studied by biopsy the bone marrow of 66 patients suffering from various cancers and suspect of marrow metastasis. Metastatic cells were thus found in 45 patients. Bone marrow composition was examined on histologic sections by granulometric method, while relative proportions and morphology of the various hematopoietic series were examined on cytologic prints. It then appeared that any important metastatic invasion goes together with deep alterations of the surrounding hematopoietic tissue, with frequent peri-metastatic collagenic fibrosis and hypoplasia of the various cell-lines; when metastatic growth is still moderate, hematopoietic tissue is, on the contrary, often hyperplastic, \"irritative\". These marrow alterations are not to be found far from the metastasis, and thus seem to be directly linked to the actual presence of cancerous cells.", "contents": "[Changes in bone marrow cellularity close to cancer metastases. Cyto-histologic study]. Before starting any therapy, we systematically studied by biopsy the bone marrow of 66 patients suffering from various cancers and suspect of marrow metastasis. Metastatic cells were thus found in 45 patients. Bone marrow composition was examined on histologic sections by granulometric method, while relative proportions and morphology of the various hematopoietic series were examined on cytologic prints. It then appeared that any important metastatic invasion goes together with deep alterations of the surrounding hematopoietic tissue, with frequent peri-metastatic collagenic fibrosis and hypoplasia of the various cell-lines; when metastatic growth is still moderate, hematopoietic tissue is, on the contrary, often hyperplastic, \"irritative\". These marrow alterations are not to be found far from the metastasis, and thus seem to be directly linked to the actual presence of cancerous cells."}
{"id": "PMID:188152", "title": "[Severe forms of so-called functional epigastric pain].", "content": "The authors report 17 severe cases of functional epigastric pain. There was a long history of severe pain with an effect on general health. It was resistant to usual symptomatic treatment. There were two special characteristics: fixity in time, and the ability to produce the pain on palpation of the region around the aorta. A psychological study showed an unusual form of neurotic decompensation occurring under special circumstances. Drug treatment in hospital gave favourable results which were maintained 2 to 5 years later on follow up.", "contents": "[Severe forms of so-called functional epigastric pain]. The authors report 17 severe cases of functional epigastric pain. There was a long history of severe pain with an effect on general health. It was resistant to usual symptomatic treatment. There were two special characteristics: fixity in time, and the ability to produce the pain on palpation of the region around the aorta. A psychological study showed an unusual form of neurotic decompensation occurring under special circumstances. Drug treatment in hospital gave favourable results which were maintained 2 to 5 years later on follow up."}
{"id": "PMID:188156", "title": "[Epileptic seizure revealing a cerebral arterial accident during administration of oral contraceptives with platelet function disorders].", "content": "The authors observed the onset of an epileptic fit in a 27 year-old woman, ten months after starting treatment with the contraceptive pill. Carotid arteriography revealed the existence of non-obstructive lesions in the area supplied by the left anterior cerebral artery. Disorders of platelet aggregation and disaggregation were demonstrated 15 days after stopping the contraceptive treatment. The significance of these abnormalities is discussed in the light of data in the literature.", "contents": "[Epileptic seizure revealing a cerebral arterial accident during administration of oral contraceptives with platelet function disorders]. The authors observed the onset of an epileptic fit in a 27 year-old woman, ten months after starting treatment with the contraceptive pill. Carotid arteriography revealed the existence of non-obstructive lesions in the area supplied by the left anterior cerebral artery. Disorders of platelet aggregation and disaggregation were demonstrated 15 days after stopping the contraceptive treatment. The significance of these abnormalities is discussed in the light of data in the literature."}
{"id": "PMID:188157", "title": "[Spontaneous septic arthritis in disseminated lupus erythematosus].", "content": "The authors report the case of a young 17 year-old girl with acute systemic lupus erythematosus who presented with purulent arthritis due to Group A hemolytic streptococcus in the knee, and perhaps other joints. She had not yet received any treatment. The purulent arthritis was cured by antibiotics. In spite of corticosteroids and immuno-suppressive agents (Chlorambucil), the patient died one year later. Spontaneous purulent arthritis is rare during systemic lupus erythematosus. We found only 8 other cases in the world literature. Contrary to our case, these were patients already treated with corticosteroid or immuno-suppressive agents. In our patient, the absence of previous treatment permitted us to incriminate the lupus itself in the onset of this infection. The conditions of onset of infection during lupus erythematosus are discussed.", "contents": "[Spontaneous septic arthritis in disseminated lupus erythematosus]. The authors report the case of a young 17 year-old girl with acute systemic lupus erythematosus who presented with purulent arthritis due to Group A hemolytic streptococcus in the knee, and perhaps other joints. She had not yet received any treatment. The purulent arthritis was cured by antibiotics. In spite of corticosteroids and immuno-suppressive agents (Chlorambucil), the patient died one year later. Spontaneous purulent arthritis is rare during systemic lupus erythematosus. We found only 8 other cases in the world literature. Contrary to our case, these were patients already treated with corticosteroid or immuno-suppressive agents. In our patient, the absence of previous treatment permitted us to incriminate the lupus itself in the onset of this infection. The conditions of onset of infection during lupus erythematosus are discussed."}
{"id": "PMID:188158", "title": "[Circulatory disorders induced by amantidine].", "content": "Amantadine has been used since 1969 in the treatment of Parkinson's disease. In 1970, were described the special symptoms noted in the lower limbs due to this drug. The authors, after a review of the various disturbances, have studied 10 cases by Capillaroscopy. They emphasize the interest of the study of this abnormality of the micro-circulation, producing vaso-constriction of the arterioles and venules.", "contents": "[Circulatory disorders induced by amantidine]. Amantadine has been used since 1969 in the treatment of Parkinson's disease. In 1970, were described the special symptoms noted in the lower limbs due to this drug. The authors, after a review of the various disturbances, have studied 10 cases by Capillaroscopy. They emphasize the interest of the study of this abnormality of the micro-circulation, producing vaso-constriction of the arterioles and venules."}
{"id": "PMID:188159", "title": "[Mixed hyperlipoproteinemias. Importance of diet].", "content": "The interest of diet is particularly clear in mixed hyperlipemia. In fact, the authors were only able to define the type of lipid abnormality after a test diet and prolonged supervision. One should never treat mixed hyperlipemia straightaway with hypocholesterolemic agents. The authors studied 22 patients with a form only demonstrable in the laboratory. There were no clinical signs of arteriosclerosis. In the group of dyslipemic subjects with minor hyperlipemia, they obtained normal figures for serum cholesterol and triglyceride. The results remained stable after 4 months supervision.", "contents": "[Mixed hyperlipoproteinemias. Importance of diet]. The interest of diet is particularly clear in mixed hyperlipemia. In fact, the authors were only able to define the type of lipid abnormality after a test diet and prolonged supervision. One should never treat mixed hyperlipemia straightaway with hypocholesterolemic agents. The authors studied 22 patients with a form only demonstrable in the laboratory. There were no clinical signs of arteriosclerosis. In the group of dyslipemic subjects with minor hyperlipemia, they obtained normal figures for serum cholesterol and triglyceride. The results remained stable after 4 months supervision."}
{"id": "PMID:188164", "title": "[Emergency surgical treatment of septal perforations in the acute phase of myocardial infarct. Apropos of 2 cases operated on successfully in the 48th hour and 5th day after development after the necrosis].", "content": "The authors report two personal cases of septal perforation during the acute phase of myocardial infarction which under medical treatment would have been rapidly fatal, and which were treated successfully by surgery on the second and fifth days respectively after the infarction, i.e. very early. After briefly recalling the main diagnostic and etiological factors of this serious complication, and the spontaneous prognosis which is usually catastrophic, they emphasise that in presence of poorly controlled heart failure and cardiogenic shock, uncontrollable by intensive medical treatment, only early surgical repair during the first few hours or days of the course of the coronary accident will permit one in certain cases to avoid a fatal issue as proved by their two cases and a review of recent publications. They emphasis the place of circulatory assistance by intraaortic balloon in the preparation of patients for operation and the methods of mycardial revascularisatin during the operation.", "contents": "[Emergency surgical treatment of septal perforations in the acute phase of myocardial infarct. Apropos of 2 cases operated on successfully in the 48th hour and 5th day after development after the necrosis]. The authors report two personal cases of septal perforation during the acute phase of myocardial infarction which under medical treatment would have been rapidly fatal, and which were treated successfully by surgery on the second and fifth days respectively after the infarction, i.e. very early. After briefly recalling the main diagnostic and etiological factors of this serious complication, and the spontaneous prognosis which is usually catastrophic, they emphasise that in presence of poorly controlled heart failure and cardiogenic shock, uncontrollable by intensive medical treatment, only early surgical repair during the first few hours or days of the course of the coronary accident will permit one in certain cases to avoid a fatal issue as proved by their two cases and a review of recent publications. They emphasis the place of circulatory assistance by intraaortic balloon in the preparation of patients for operation and the methods of mycardial revascularisatin during the operation."}
{"id": "PMID:188165", "title": "[Cerebromeningeal hemorrhages and their sequelae in congenital deficiencies of plasma hemostasis factors. Apropos of a case of Stuart factor deficiency with early cerebromengeal hemorrhage leading to hydrocephalus with considerable psychomotor retardation].", "content": "We have taken an interest in cerebro meningeal haemorrhages in congenital plasmatic coagulation Factor deficiency with out obvious traumatic origin. We have observed such accidents in a new born child with congenital Stuart factor deficiency and in four cases of haemophilia A. It seems from our experience and from the literature that such haemorragic accidents are not particularly frequent in congenital coagulation deficiency and contribute only for a few to creation of a psychomotor inadapted population.", "contents": "[Cerebromeningeal hemorrhages and their sequelae in congenital deficiencies of plasma hemostasis factors. Apropos of a case of Stuart factor deficiency with early cerebromengeal hemorrhage leading to hydrocephalus with considerable psychomotor retardation]. We have taken an interest in cerebro meningeal haemorrhages in congenital plasmatic coagulation Factor deficiency with out obvious traumatic origin. We have observed such accidents in a new born child with congenital Stuart factor deficiency and in four cases of haemophilia A. It seems from our experience and from the literature that such haemorragic accidents are not particularly frequent in congenital coagulation deficiency and contribute only for a few to creation of a psychomotor inadapted population."}
{"id": "PMID:188168", "title": "[Effects of the nervous system on the kidney. Part I. Review of the literature].", "content": "The authors review the literature on the effects of the nervous system on the kidney in 3 stages: 1) Historical stage when the role of the renal nerve supply was overetimated by Claude Bernard. 2) Intermediate stage between the two wars with a clinical description of uremic encephalits or acute delirium. From the experimental point of view was demonstrated the inessential character of the nerve supply for the survival of the kidney. 3) Modern stage: from the clinical point of view one may distinguish functional nephropathies including those of nervous origin. The latter are due to metabolic or vascular mechanisms which are intricated to various degrees. Problems of regulation are raised in man by certain findings.", "contents": "[Effects of the nervous system on the kidney. Part I. Review of the literature]. The authors review the literature on the effects of the nervous system on the kidney in 3 stages: 1) Historical stage when the role of the renal nerve supply was overetimated by Claude Bernard. 2) Intermediate stage between the two wars with a clinical description of uremic encephalits or acute delirium. From the experimental point of view was demonstrated the inessential character of the nerve supply for the survival of the kidney. 3) Modern stage: from the clinical point of view one may distinguish functional nephropathies including those of nervous origin. The latter are due to metabolic or vascular mechanisms which are intricated to various degrees. Problems of regulation are raised in man by certain findings."}
{"id": "PMID:188169", "title": "[Study of factors favoring infection in total hip prosthesis. Twenty-five observations].", "content": "The authors report 25 cases of infection following total hip replacement and individual factors are analysed. The role of immunological abnormalities is discussed. They distinguish early infection due to the operative conditions from late infection where individual factors are the most important. A few preventive measures are proposed, they emphasise the necessity of a large scale study of factors favouring late infection.", "contents": "[Study of factors favoring infection in total hip prosthesis. Twenty-five observations]. The authors report 25 cases of infection following total hip replacement and individual factors are analysed. The role of immunological abnormalities is discussed. They distinguish early infection due to the operative conditions from late infection where individual factors are the most important. A few preventive measures are proposed, they emphasise the necessity of a large scale study of factors favouring late infection."}
{"id": "PMID:188173", "title": "[Eosinophilic leukemia and disseminated intravascular coagulation].", "content": "Eosinophil leukemia is still an uncertain entity owing to the lack of specific markers for malignancy. The authors report a case with increased serum vitamin B12 and intravascular coagulation, and discuss the value of these two abnormalities as functional markers.", "contents": "[Eosinophilic leukemia and disseminated intravascular coagulation]. Eosinophil leukemia is still an uncertain entity owing to the lack of specific markers for malignancy. The authors report a case with increased serum vitamin B12 and intravascular coagulation, and discuss the value of these two abnormalities as functional markers."}
{"id": "PMID:188174", "title": "[Clostridium perfringens infection. Problems posed excluding resuscitation].", "content": "The authors report 18 cases of Clostridium perfringens infection and discuss the main clinical and etiological aspects apart from gynecological forms and those usually requiring intensive care. Pathological foci, digestive infection and the problem of bacteremia are discussed together with appropriate treatment.", "contents": "[Clostridium perfringens infection. Problems posed excluding resuscitation]. The authors report 18 cases of Clostridium perfringens infection and discuss the main clinical and etiological aspects apart from gynecological forms and those usually requiring intensive care. Pathological foci, digestive infection and the problem of bacteremia are discussed together with appropriate treatment."}
{"id": "PMID:188176", "title": "[Alternating low calory diets (200 to 1000 calories), their value in the treatment of resistant obesity].", "content": "In obesity resistant to traditional low calory diets, the authors alternated short periods of moderate low calory intake (600 to 1,000 calories) with periods of very restrictive low calory intake (230 to 300 calories). The results of this method are analysed in 105 patients. This method permits loss of weight in difficult cases of obesity, both during intensely low calory diets and during less severe low calory diets. This technique is well accepted by the patients and is less monotonous than very unbalanced multi-fractionated diets or with prolonged courses of fasting. The results are all the more satisfactory when the patient is young, when the obesity is recent and marked, which does not, however, exclude its efficacy in long-standing cases of obesity.", "contents": "[Alternating low calory diets (200 to 1000 calories), their value in the treatment of resistant obesity]. In obesity resistant to traditional low calory diets, the authors alternated short periods of moderate low calory intake (600 to 1,000 calories) with periods of very restrictive low calory intake (230 to 300 calories). The results of this method are analysed in 105 patients. This method permits loss of weight in difficult cases of obesity, both during intensely low calory diets and during less severe low calory diets. This technique is well accepted by the patients and is less monotonous than very unbalanced multi-fractionated diets or with prolonged courses of fasting. The results are all the more satisfactory when the patient is young, when the obesity is recent and marked, which does not, however, exclude its efficacy in long-standing cases of obesity."}
{"id": "PMID:188177", "title": "[Mediastinopulmonary sarcoidosis; the indications for corticosteroid therapy].", "content": "The authors, following prolonged observation for from one to ten years, on average 5 years, of 60 cases of thoracic sarcoidosis, of lymph node or miliary type, propose a therapeutic attitude which, although not new, is frankly oriented towards therapeutic abstinence in the lymph node forms, and very restricted indications for hormone therapy in the miliary forms. In this respect, they agree with many authors, in particular English language authors, who consider that corticosteroid therapy is only justified in the acute forms, with a disturbance of general health and characteristic functional involvement. Such an attitude may appear shocking to those who tend to prescribe corticosteroids for their immediate efficacy, but in the long-term, it appears justified.", "contents": "[Mediastinopulmonary sarcoidosis; the indications for corticosteroid therapy]. The authors, following prolonged observation for from one to ten years, on average 5 years, of 60 cases of thoracic sarcoidosis, of lymph node or miliary type, propose a therapeutic attitude which, although not new, is frankly oriented towards therapeutic abstinence in the lymph node forms, and very restricted indications for hormone therapy in the miliary forms. In this respect, they agree with many authors, in particular English language authors, who consider that corticosteroid therapy is only justified in the acute forms, with a disturbance of general health and characteristic functional involvement. Such an attitude may appear shocking to those who tend to prescribe corticosteroids for their immediate efficacy, but in the long-term, it appears justified."}
{"id": "PMID:188178", "title": "[Toxic thyroid adenoma and malignant hypercalcemia of parathyroid origin].", "content": "Malignant hypercalcemia due to the association of hyperthyroidism and hyperparathyroidism is rare. We report a case with a fatal course in spite of surgical treatment of both lesions. Death occurred seven days after the operation due to ventricular tachycardia, in spite of return to normal of the calcemia, the serum phosphorus, the serum electrolytes and relief of the thyro-toxicosis. There is a great deal of histopathological evidence for the association of a toxic parathyroid carcinoma and a thyroid adenoma.", "contents": "[Toxic thyroid adenoma and malignant hypercalcemia of parathyroid origin]. Malignant hypercalcemia due to the association of hyperthyroidism and hyperparathyroidism is rare. We report a case with a fatal course in spite of surgical treatment of both lesions. Death occurred seven days after the operation due to ventricular tachycardia, in spite of return to normal of the calcemia, the serum phosphorus, the serum electrolytes and relief of the thyro-toxicosis. There is a great deal of histopathological evidence for the association of a toxic parathyroid carcinoma and a thyroid adenoma."}
{"id": "PMID:188179", "title": "[IgM myeloma].", "content": "The authors report the case of a 62 year old woman in whom bony pain led to the discovery of lacunar osteolytic appearances, in particular in the skull, abnormal medullary plasmacytosis and serum monoclonal immunoglobulin with Bence-Jones proteinuria. The case was unusual as the immunoglobulin observed was an IgM. This finding led the authors to a critical revision of the distinctive characteristics of multiple myeloma and Waldenstr\u00f6m's macro-globulinemia, emphasizing the distinguishing value of the cytological criterion. The authors recall the various neoplastic proliferations of the B lymphocytes at the various stages of their maturation and emphasize the predominance of monoclonal IgM during proliferations affecting the early stages of maturation of the B lymphocytes and the rareness of these IgM during plasma cell neoplasms.", "contents": "[IgM myeloma]. The authors report the case of a 62 year old woman in whom bony pain led to the discovery of lacunar osteolytic appearances, in particular in the skull, abnormal medullary plasmacytosis and serum monoclonal immunoglobulin with Bence-Jones proteinuria. The case was unusual as the immunoglobulin observed was an IgM. This finding led the authors to a critical revision of the distinctive characteristics of multiple myeloma and Waldenstr\u00f6m's macro-globulinemia, emphasizing the distinguishing value of the cytological criterion. The authors recall the various neoplastic proliferations of the B lymphocytes at the various stages of their maturation and emphasize the predominance of monoclonal IgM during proliferations affecting the early stages of maturation of the B lymphocytes and the rareness of these IgM during plasma cell neoplasms."}
{"id": "PMID:188180", "title": "[Clinical aspects and course of drug-induced upper digestive hemorrhage].", "content": "In a series of 500 patients admitted to hospital for upper digestive hemorrhage, the authors studied the influence of taking drugs on the clinical characteristics and course of the original disease. Taking aspirin is exceptional before rupture of esophageal varices. One may isolate a homogenous group of elderly women consuming aspirin and another anti-inflammatory drug, and bleeding from a gastric ulcer. One may also isolate another group of men, bleeding from acute gastro-duodenal lesions after taking aspirin alone. If one considers apart portal hypertension, owing to its extreme gravity, one may note that the prognosis depends on the age. One patient out of five, dies of hemorrhage after the age of 60 years. Taking an anti-inflammatory drug at this age is thus not harmless.", "contents": "[Clinical aspects and course of drug-induced upper digestive hemorrhage]. In a series of 500 patients admitted to hospital for upper digestive hemorrhage, the authors studied the influence of taking drugs on the clinical characteristics and course of the original disease. Taking aspirin is exceptional before rupture of esophageal varices. One may isolate a homogenous group of elderly women consuming aspirin and another anti-inflammatory drug, and bleeding from a gastric ulcer. One may also isolate another group of men, bleeding from acute gastro-duodenal lesions after taking aspirin alone. If one considers apart portal hypertension, owing to its extreme gravity, one may note that the prognosis depends on the age. One patient out of five, dies of hemorrhage after the age of 60 years. Taking an anti-inflammatory drug at this age is thus not harmless."}
{"id": "PMID:188181", "title": "[Preliminary psychological survey in the study of cardiac rehabilitation through controlled physical activity].", "content": "The authors carried out an enquiry in 32 patients as part of a more extensive study which permitted them to show the necessity of early physical rehabilitation after myocardial infarction which should be gradual and as prolonged as possible under permanent medical control. Subjects under training usually adhere enthusiastically to this program of progressively complete and rapid social reinsertion, by the development of new relationships, whether personal, familial or professional.", "contents": "[Preliminary psychological survey in the study of cardiac rehabilitation through controlled physical activity]. The authors carried out an enquiry in 32 patients as part of a more extensive study which permitted them to show the necessity of early physical rehabilitation after myocardial infarction which should be gradual and as prolonged as possible under permanent medical control. Subjects under training usually adhere enthusiastically to this program of progressively complete and rapid social reinsertion, by the development of new relationships, whether personal, familial or professional."}
{"id": "PMID:188184", "title": "[Colonic cancer and diverticulitis of the large intestine].", "content": "The authors report 17 cases of colonic carcinoma associated with diverticulitis. They differentiate between carcinomas arising above and below the diverticular area and emphasise the coexistence of both diseases on the same segment of colon. The diagnosis may be made in two different circumstances depending on whether the association presents as diverticulosis or as diverticulitis with  complications. Careful examination of the barium enema whenever possible is the basic factor in diagnosis. The operation is rendered more difficult by inflammatory phenomena or suppuration of the sigmoiditis and the prognosis is aggravated by cancer.", "contents": "[Colonic cancer and diverticulitis of the large intestine]. The authors report 17 cases of colonic carcinoma associated with diverticulitis. They differentiate between carcinomas arising above and below the diverticular area and emphasise the coexistence of both diseases on the same segment of colon. The diagnosis may be made in two different circumstances depending on whether the association presents as diverticulosis or as diverticulitis with  complications. Careful examination of the barium enema whenever possible is the basic factor in diagnosis. The operation is rendered more difficult by inflammatory phenomena or suppuration of the sigmoiditis and the prognosis is aggravated by cancer."}
{"id": "PMID:188185", "title": "[Reflexions on the surgical treatment of diverticular sigmoiditis. Apropos of 62 cases].", "content": "The authors report 62 cases of operated diverticular sigmoiditis, note the indications for surgery and the method adopted. Apart from acute complications comparison of the clinical, laboratory and radiological data permit one to decide on a cold operation for prophylactic purposes. For acute generalised or localised peritonitis, the authors remove the lesions straight away when local and general conditions permit it. They emphasis the severity of the complications and the dealy with which these patients are still too often admitted on a surgical unit, which explins the persistently poor prognosis in spite of present conditions of resuscitation.", "contents": "[Reflexions on the surgical treatment of diverticular sigmoiditis. Apropos of 62 cases]. The authors report 62 cases of operated diverticular sigmoiditis, note the indications for surgery and the method adopted. Apart from acute complications comparison of the clinical, laboratory and radiological data permit one to decide on a cold operation for prophylactic purposes. For acute generalised or localised peritonitis, the authors remove the lesions straight away when local and general conditions permit it. They emphasis the severity of the complications and the dealy with which these patients are still too often admitted on a surgical unit, which explins the persistently poor prognosis in spite of present conditions of resuscitation."}
{"id": "PMID:188186", "title": "[Chyloperitoneum causing intestinal obstruction].", "content": "The two cases reported here show intestinal obstruction may occur by coagulation of lymph around the loops. They permit us to better understand the physiopathology of blockage of the lymph vessels whether congenital as in the first case or traumatic as in the second case. Traumatic rupture of the cisterns chyli is exceptional. The histological lesions observed on clamped biopsies show clearly the pathology of protein-losing enteropathy.", "contents": "[Chyloperitoneum causing intestinal obstruction]. The two cases reported here show intestinal obstruction may occur by coagulation of lymph around the loops. They permit us to better understand the physiopathology of blockage of the lymph vessels whether congenital as in the first case or traumatic as in the second case. Traumatic rupture of the cisterns chyli is exceptional. The histological lesions observed on clamped biopsies show clearly the pathology of protein-losing enteropathy."}
{"id": "PMID:188187", "title": "[Spontaneous pneumothorax in women].", "content": "Among cases of spontaneous pneumothorax, female cases are extremely rare. They represent only about 10% of observed cases and form a special clinical type. The authors discuss 20 cases out of a total of 261 cases of pneumothorax observed over a period of 7 years. A certain number of facts were noted which distinguished the female forms from the male forms of this disease. Although there is no difference in the symptoms, the disease tends to occur later in women, in the fourth decade of life, and only three of the 20 cases in this series were idiopathic. On the other hand, among the secondary cases, the frequency of E.N.T. or respiratory disease is remarkable for it concerned 75% of cases. None of the cases observed responded to the usual criteria of menstrual pneumothorax although seven occurred during the menstrual period. However the forms which relapse during the periods should lead to a search for pelvic endometriosis. Finally the proportion of rib malformations is not negligible. These facts emphasise that pneumothorax in women, contrary to men, appears much more as a complication of another disease than as an autonomous pleural disease.", "contents": "[Spontaneous pneumothorax in women]. Among cases of spontaneous pneumothorax, female cases are extremely rare. They represent only about 10% of observed cases and form a special clinical type. The authors discuss 20 cases out of a total of 261 cases of pneumothorax observed over a period of 7 years. A certain number of facts were noted which distinguished the female forms from the male forms of this disease. Although there is no difference in the symptoms, the disease tends to occur later in women, in the fourth decade of life, and only three of the 20 cases in this series were idiopathic. On the other hand, among the secondary cases, the frequency of E.N.T. or respiratory disease is remarkable for it concerned 75% of cases. None of the cases observed responded to the usual criteria of menstrual pneumothorax although seven occurred during the menstrual period. However the forms which relapse during the periods should lead to a search for pelvic endometriosis. Finally the proportion of rib malformations is not negligible. These facts emphasise that pneumothorax in women, contrary to men, appears much more as a complication of another disease than as an autonomous pleural disease."}
{"id": "PMID:188191", "title": "Fanconi's anemia: chromosome anormalies.", "content": "Two types of chromosome abnormalitie are observed in the bone marrow and the blood of a patient with Fanconi's anemia. There abnormalities involved in two stages: firstly the presence of a clone with 47 chromosomes + 21, which was not found during later examinations. One and a half years later, following a decline in the hematological condition, there appeared duplication of certain chromosome segments of the long arm of the 3 chromosome and of the intermediate segment of the long arm of the 12 chromosome. This latter type of abnormality affected differently the bone marrow and the blood in the bone marrow, we found 2 clones, one bore 2 markers obtained from 3 and 12, the other and marker obtained from the 12 chromosome. In the blood, there was simply a minority clone with only the marker originating in the 3 chromosome. This observation should be compared with the descriptions made by other authors. In all cases abnormal clones present an apparently unbalanced karyotype, characterised by excess material.", "contents": "Fanconi's anemia: chromosome anormalies. Two types of chromosome abnormalitie are observed in the bone marrow and the blood of a patient with Fanconi's anemia. There abnormalities involved in two stages: firstly the presence of a clone with 47 chromosomes + 21, which was not found during later examinations. One and a half years later, following a decline in the hematological condition, there appeared duplication of certain chromosome segments of the long arm of the 3 chromosome and of the intermediate segment of the long arm of the 12 chromosome. This latter type of abnormality affected differently the bone marrow and the blood in the bone marrow, we found 2 clones, one bore 2 markers obtained from 3 and 12, the other and marker obtained from the 12 chromosome. In the blood, there was simply a minority clone with only the marker originating in the 3 chromosome. This observation should be compared with the descriptions made by other authors. In all cases abnormal clones present an apparently unbalanced karyotype, characterised by excess material."}
{"id": "PMID:188192", "title": "[Pitfalls of the normal electrocardiogram].", "content": "The authors report the cases of 7 patients with a normal basal electrocardiogram, whereas they were all affected with a high risk cardiovascular condition: coronary insufficiency in 3 cases, paroxysmal arrhythmia in 4 cases. They recall the limits of the conventional ECG and emphasise interest of dynamic recordings, with effort tests, and/on continuous ECG recording in the identification of certain transient heart manifestations.", "contents": "[Pitfalls of the normal electrocardiogram]. The authors report the cases of 7 patients with a normal basal electrocardiogram, whereas they were all affected with a high risk cardiovascular condition: coronary insufficiency in 3 cases, paroxysmal arrhythmia in 4 cases. They recall the limits of the conventional ECG and emphasise interest of dynamic recordings, with effort tests, and/on continuous ECG recording in the identification of certain transient heart manifestations."}
{"id": "PMID:188193", "title": "[Obliterating parietal hemodissection or vertebro-basilar dissecting aneurysm].", "content": "The authors report the pathological and clinical findings of a dissecting aneursym of the basilar artery in a 32 year old man up till then in good health, who died two months later. The pathological study showed bilateral lesions of osteo-malacia in the neighborhood of the pons due to hemo-dissection affecting the right vertebral artery just before it enters the dura-mater, then its intra-cranial portion, the basilar trunk and the first part of the right posterior cerebral artery. The originality of this case resides in the finding of segmental stenosing panarteritis of the same right vertebral artery in the segment which precedes dissection. On this occasion, the authors carried out a review of the literature and considered a few comments on the etiology, the pathology, clinical findings and classification of this unusual disease.", "contents": "[Obliterating parietal hemodissection or vertebro-basilar dissecting aneurysm]. The authors report the pathological and clinical findings of a dissecting aneursym of the basilar artery in a 32 year old man up till then in good health, who died two months later. The pathological study showed bilateral lesions of osteo-malacia in the neighborhood of the pons due to hemo-dissection affecting the right vertebral artery just before it enters the dura-mater, then its intra-cranial portion, the basilar trunk and the first part of the right posterior cerebral artery. The originality of this case resides in the finding of segmental stenosing panarteritis of the same right vertebral artery in the segment which precedes dissection. On this occasion, the authors carried out a review of the literature and considered a few comments on the etiology, the pathology, clinical findings and classification of this unusual disease."}
{"id": "PMID:188194", "title": "[L\u00f6fgren's syndrome, sarcoidosis and Bouillaud's disease].", "content": "The authors report two cases of L\u00f6fgren's syndrome, preceded by febrile polyarthritis with rise in antistreptolysin titer. The relationship between sarcoidosis and rheumatic fever is discussed. A review of the literature concerning L\u00f6fgren's syndrome with joint pain, permitted the authors to follow the course of present pathogenic concepts which haveled to the present opinion of the sarcoidosis nature of L\u00f6fgren's syndrome, when the latter is accompanied by erythema nodosum. The prolonged rise in antistreptolysin 0 titer which might suggest rheumatic fever, was not explained, but as the streptococcus was never found in throat swabs, it is probable that this was a non-specific phenomenon. However, certain authors believe that streptococcal infection, where it exists, may play a role, if not in the etiology of the sarcoidosis, at least in the L\u00f6fgren's syndrome which may lead to its discovery.", "contents": "[L\u00f6fgren's syndrome, sarcoidosis and Bouillaud's disease]. The authors report two cases of L\u00f6fgren's syndrome, preceded by febrile polyarthritis with rise in antistreptolysin titer. The relationship between sarcoidosis and rheumatic fever is discussed. A review of the literature concerning L\u00f6fgren's syndrome with joint pain, permitted the authors to follow the course of present pathogenic concepts which haveled to the present opinion of the sarcoidosis nature of L\u00f6fgren's syndrome, when the latter is accompanied by erythema nodosum. The prolonged rise in antistreptolysin 0 titer which might suggest rheumatic fever, was not explained, but as the streptococcus was never found in throat swabs, it is probable that this was a non-specific phenomenon. However, certain authors believe that streptococcal infection, where it exists, may play a role, if not in the etiology of the sarcoidosis, at least in the L\u00f6fgren's syndrome which may lead to its discovery."}
{"id": "PMID:188195", "title": "[Study of insulin secretion in chronic pancreatitis].", "content": "17 oral glucose tolerance tests with simultaneous estimation of plasma insulin, were carried out in 15 patients with chronic pancreatitis of which 7 were of calcific type. Among these patients, 10 had obvious diabetes and 3 chemical diabetes. The disorders of glucose regulation were more common in the calcific form of the disease. Serum insulin was then lower and not stimulant. The curves of plasma insulin obtained in non-calcific pancreatitis were variable. In hyperinsulinism, the oral glucose tolerance test showed flat or normal curves. In hypoinsulinism, the glucose tolerance tests were either normal or strongly pathological. This insulinism, as shown by this study of chronic pancreatitis, seems to be linked to an imbalance in the cell distribution of the islets of Langerhans. The role of glucagon appears preponderant.", "contents": "[Study of insulin secretion in chronic pancreatitis]. 17 oral glucose tolerance tests with simultaneous estimation of plasma insulin, were carried out in 15 patients with chronic pancreatitis of which 7 were of calcific type. Among these patients, 10 had obvious diabetes and 3 chemical diabetes. The disorders of glucose regulation were more common in the calcific form of the disease. Serum insulin was then lower and not stimulant. The curves of plasma insulin obtained in non-calcific pancreatitis were variable. In hyperinsulinism, the oral glucose tolerance test showed flat or normal curves. In hypoinsulinism, the glucose tolerance tests were either normal or strongly pathological. This insulinism, as shown by this study of chronic pancreatitis, seems to be linked to an imbalance in the cell distribution of the islets of Langerhans. The role of glucagon appears preponderant."}
{"id": "PMID:188205", "title": "The effect of long-term oestrogen replacement therapy on glucose and lipid metabolism in postmenopausal women.", "content": "A prospective study was undertaken to determine the effect on carbohydrate and lipid metabolism of long-term oestrogen replacement therapy in an unselected group of 34 postmenopausal women. Treatment was with cyclically-administered conjugated oestrogen (1,25 mg daily) for 24-43 months. Each patient served as her own control. The mean 2-hour postglucose level for the group at the end of the study was greater than the original baseline values, but the difference was not statistically significant. The mean serum cholesterol pre-beta-lipoprotein and beta-lipoprotein levels for the group were significantly reduced. Triglycerides were unaffected. It is suggested that treatment with conjugated oestrogens can maintain a normal lipid profile, provided that the original levels are within normal limits and that therapy is instituted early and is maintained. Carbohydrate and lipid metabolism in the majority of postmenopausal women on long-term conjugated oestrogen therapy will not be adversely affected.", "contents": "The effect of long-term oestrogen replacement therapy on glucose and lipid metabolism in postmenopausal women. A prospective study was undertaken to determine the effect on carbohydrate and lipid metabolism of long-term oestrogen replacement therapy in an unselected group of 34 postmenopausal women. Treatment was with cyclically-administered conjugated oestrogen (1,25 mg daily) for 24-43 months. Each patient served as her own control. The mean 2-hour postglucose level for the group at the end of the study was greater than the original baseline values, but the difference was not statistically significant. The mean serum cholesterol pre-beta-lipoprotein and beta-lipoprotein levels for the group were significantly reduced. Triglycerides were unaffected. It is suggested that treatment with conjugated oestrogens can maintain a normal lipid profile, provided that the original levels are within normal limits and that therapy is instituted early and is maintained. Carbohydrate and lipid metabolism in the majority of postmenopausal women on long-term conjugated oestrogen therapy will not be adversely affected."}
{"id": "PMID:188206", "title": "Topographical anatomy of human cerebral and cerebellar astrocytomas in vitro.", "content": "This study further characterizes the morphological and in vitro properties of human neoplastic cells derived from one Grade IV cerebral astrocytoma and one Grade III cerebellar astrocytoma. Light microscopic observations performed weekly over a four month period revealed two morphologically indistinguishable cell populations in each of the tumor cultures. Scanning electron microscopy demonstrated the presence of microvilli, blegs, and ruffles on the cell surfaces of both tumors; however, these topographical features were more prominent in the cultures derived from the Grade III cerebellar astrocytoma. Scanning electron microscopy may provide a useful tool for the further morphologic classification of human astrocytomas.", "contents": "Topographical anatomy of human cerebral and cerebellar astrocytomas in vitro. This study further characterizes the morphological and in vitro properties of human neoplastic cells derived from one Grade IV cerebral astrocytoma and one Grade III cerebellar astrocytoma. Light microscopic observations performed weekly over a four month period revealed two morphologically indistinguishable cell populations in each of the tumor cultures. Scanning electron microscopy demonstrated the presence of microvilli, blegs, and ruffles on the cell surfaces of both tumors; however, these topographical features were more prominent in the cultures derived from the Grade III cerebellar astrocytoma. Scanning electron microscopy may provide a useful tool for the further morphologic classification of human astrocytomas."}
{"id": "PMID:188207", "title": "Fibrous dysplasia of the skull with progressive cranial nerve involvement.", "content": "The purpose of this report is twofold. First, to discuss fibrous dysplasia of bone as it relates to the neurosurgeon, and second to present a case of fibrous dysplasia of the skull with progressive involvement of the optic and trigeminal nerves. Of special interest in this case is the progression of the disease after puberty and the technical problems of decompression of the involved nerves. A combined approach to the lesion with otolaryngological assistance was undertaken.", "contents": "Fibrous dysplasia of the skull with progressive cranial nerve involvement. The purpose of this report is twofold. First, to discuss fibrous dysplasia of bone as it relates to the neurosurgeon, and second to present a case of fibrous dysplasia of the skull with progressive involvement of the optic and trigeminal nerves. Of special interest in this case is the progression of the disease after puberty and the technical problems of decompression of the involved nerves. A combined approach to the lesion with otolaryngological assistance was undertaken."}
{"id": "PMID:188222", "title": "Pulmonary blastoma.", "content": "A primary pulmonary tumour in a four year old boy arising from the subpleural zone of the lung is described. It contains both stromal and epithelial elements at the primary site and in the bony metastases. The combination of the age of the patient, the site of the tumour, the stromal and epithelial elements present in the tumour suggest that this is a true pulmonary blastoma. Electronmicroscopy showed the presence of intranuclear viral particles.", "contents": "Pulmonary blastoma. A primary pulmonary tumour in a four year old boy arising from the subpleural zone of the lung is described. It contains both stromal and epithelial elements at the primary site and in the bony metastases. The combination of the age of the patient, the site of the tumour, the stromal and epithelial elements present in the tumour suggest that this is a true pulmonary blastoma. Electronmicroscopy showed the presence of intranuclear viral particles."}
{"id": "PMID:188223", "title": "Myocardial degeneration in mice treated with dibutyryl cyclic AMP and/or theophylline.", "content": "Fibrinoid degeneration of myocardial fibrils was induced in BALB/c mice treated from 2 months of age with weekly injection of dibutyryl cyclic DAMP and/or theophylline. No evidence of cellular reaction or vascular occlusion was found.", "contents": "Myocardial degeneration in mice treated with dibutyryl cyclic AMP and/or theophylline. Fibrinoid degeneration of myocardial fibrils was induced in BALB/c mice treated from 2 months of age with weekly injection of dibutyryl cyclic DAMP and/or theophylline. No evidence of cellular reaction or vascular occlusion was found."}
{"id": "PMID:188224", "title": "Effect of storage and in vitro ischemia on the ultrasture of microsomal membranes and on microsomal enzymes.", "content": "Pieces of liver (in vitro ischemia) and isolated microsomes were subjected to incubation at 4 degrees C and 37 degrees C for various time intervals. The effects on microsomal protein, phospholipids, and cholesterol and on microsomal phosphatases and electron transport enzymes were followed as a functional of time and temperature. NADH-cytochrome c reductase was very labile and was completely inactivated by 1 h, whereas G6Pase lost 50% of its activity after 2 h at 37 degrees C. IDPase and NADPH-cyt. c red. were of intermediate susceptibility whereas cytochromes b5 and P-450 were the most stable enzymes assayed. After 24 h of incubation of isolated microsomes at 37 degrees C there was no significant detachment of membrane components (protein, PLP or cholesterol), indicating that the inactivation of the enzymes was not primarily attributable to their solubilization. Instead, experiments with 14C-leucine and 14C-glycerol prelabeled microsomes demonstrated that the proteins detached from microsomes during incubation originated mainly from the intravesicular space due to repture of the microsomal membranes. The addition of a lysosomal extract during incubation did not alter either the rate of inactivation of the enzymes or the proportion of solubilized membrane components indicating that attack from the outside by proteolytic enzymes is not the mechanism for enzyme inactivation. There was no apparent correlation between the rates of inactivation of enzymes in vitro and their calculated half-lives in vivo or their postulated intramembranous localization. Ultrastructurally, enzyme inactivation was initially associated with alterations of the microsomal membranes, such as vesicle aggregation, membrane rupture, loss of unit membrane structure, and subsequently, thickening of membranes and transformation of the microsomes into nonrecognizable amorphous material.", "contents": "Effect of storage and in vitro ischemia on the ultrasture of microsomal membranes and on microsomal enzymes. Pieces of liver (in vitro ischemia) and isolated microsomes were subjected to incubation at 4 degrees C and 37 degrees C for various time intervals. The effects on microsomal protein, phospholipids, and cholesterol and on microsomal phosphatases and electron transport enzymes were followed as a functional of time and temperature. NADH-cytochrome c reductase was very labile and was completely inactivated by 1 h, whereas G6Pase lost 50% of its activity after 2 h at 37 degrees C. IDPase and NADPH-cyt. c red. were of intermediate susceptibility whereas cytochromes b5 and P-450 were the most stable enzymes assayed. After 24 h of incubation of isolated microsomes at 37 degrees C there was no significant detachment of membrane components (protein, PLP or cholesterol), indicating that the inactivation of the enzymes was not primarily attributable to their solubilization. Instead, experiments with 14C-leucine and 14C-glycerol prelabeled microsomes demonstrated that the proteins detached from microsomes during incubation originated mainly from the intravesicular space due to repture of the microsomal membranes. The addition of a lysosomal extract during incubation did not alter either the rate of inactivation of the enzymes or the proportion of solubilized membrane components indicating that attack from the outside by proteolytic enzymes is not the mechanism for enzyme inactivation. There was no apparent correlation between the rates of inactivation of enzymes in vitro and their calculated half-lives in vivo or their postulated intramembranous localization. Ultrastructurally, enzyme inactivation was initially associated with alterations of the microsomal membranes, such as vesicle aggregation, membrane rupture, loss of unit membrane structure, and subsequently, thickening of membranes and transformation of the microsomes into nonrecognizable amorphous material."}
{"id": "PMID:188225", "title": "Electron probe x-ray analysis of siderosomes in the rabbit haemarthrotic synovial membrane.", "content": "Electron probe x-ray analysis of siderosomes produced in the rabbit synovial membrane by repeated injections of autologous blood revealed two kinds of siderosomes; (1) those containing a small amount of phosphorus and, (2) those in which no phosphorus was detectable. On the basis of these findings and past studies it is concluded that haemosiderin is an inorganic compound of iron, probably a hydrated ferric oxide and that a variable amount of organic material (proteins, lipids, phospholipids, etc.,) probably occurs in company with the haemosiderin in the siderosome, but these variable components which decrease in amount with the passage of time cannot be considered as an integral part of haemosiderin.", "contents": "Electron probe x-ray analysis of siderosomes in the rabbit haemarthrotic synovial membrane. Electron probe x-ray analysis of siderosomes produced in the rabbit synovial membrane by repeated injections of autologous blood revealed two kinds of siderosomes; (1) those containing a small amount of phosphorus and, (2) those in which no phosphorus was detectable. On the basis of these findings and past studies it is concluded that haemosiderin is an inorganic compound of iron, probably a hydrated ferric oxide and that a variable amount of organic material (proteins, lipids, phospholipids, etc.,) probably occurs in company with the haemosiderin in the siderosome, but these variable components which decrease in amount with the passage of time cannot be considered as an integral part of haemosiderin."}
{"id": "PMID:188226", "title": "Lipid droplets of interstitial medullary cells of intact rat kidney with two-kidney Goldblatt hypertension.", "content": "Electron microscopic studies have been carried out of the interstitial cells (IC) of the renal medulla in rats with Goldblatt hypertension. Analysis of variance has not revealed any differences in the number of droplets of \"unclamped\" kidney in the hypertensive rats as compared to the normotensive rats (\"resistant\" rats, rats with unilateral nephrectomy, and intact rats) at periods from 3 weeks to 1 year. The total volume of the droplets in the IC cytoplasm in hypertensive and intact animals also revealed no difference 3 weeks after the beginning of the experiment. A positive correlation has been found between the number of the droplets and their volume but the low value of the correlation coefficient (r = +0.28) suggests that the number of the droplets cannot be a reliable indicator of the variation of the amount (volume) of thelipid material contained in them. Since it is just the latter parameter that carries the most information for evaluating the content of the droplet material in the IC, preference should be given to calculating the droplet volume rather than counting the number of droplets. The IC in the animals of the experimental groups revealed hypertrophy and hyperlasia of the endoplasmic reticulum and the Golgi complex, which were especially marked at the earlier stages of the experiments.", "contents": "Lipid droplets of interstitial medullary cells of intact rat kidney with two-kidney Goldblatt hypertension. Electron microscopic studies have been carried out of the interstitial cells (IC) of the renal medulla in rats with Goldblatt hypertension. Analysis of variance has not revealed any differences in the number of droplets of \"unclamped\" kidney in the hypertensive rats as compared to the normotensive rats (\"resistant\" rats, rats with unilateral nephrectomy, and intact rats) at periods from 3 weeks to 1 year. The total volume of the droplets in the IC cytoplasm in hypertensive and intact animals also revealed no difference 3 weeks after the beginning of the experiment. A positive correlation has been found between the number of the droplets and their volume but the low value of the correlation coefficient (r = +0.28) suggests that the number of the droplets cannot be a reliable indicator of the variation of the amount (volume) of thelipid material contained in them. Since it is just the latter parameter that carries the most information for evaluating the content of the droplet material in the IC, preference should be given to calculating the droplet volume rather than counting the number of droplets. The IC in the animals of the experimental groups revealed hypertrophy and hyperlasia of the endoplasmic reticulum and the Golgi complex, which were especially marked at the earlier stages of the experiments."}
{"id": "PMID:188227", "title": "Studies on the pathophysiology of acute renal failure. II. A histochemical study of the proximal tubule of the rat following administration of mercuric chloride.", "content": "Acute renal failure was induced in male rats by the subcutaneous injectioon of 4 mg HgC12 per kg body weight. Enzyme activities of the proximal tubule were studied histochemically at six time intervals from 15 min to 24 h. The enzyme studied were alkaline phosphatase, 5'-nucleotidase, acid phosphatase, alpha-glycerophosphate dehydrogenase (NAD-independent), malic dehydrogenase, succinic dehydrogenase, latic dehydrogenase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase. Decreases in activity were observed for alkaline phosphatase and 5'-nucleotidase after 15 min. Acid phosphatase was decreased after 30 min. These three enzymes returned to control levels after 3 h, but malic dehydrogenase and alpha-glycerophosphate dehydrogenase were decreased at this time interval. Succinic dehydrogenase was first decreased after 6 h. The earliest morphological changes detectable by light microscopy were observed in pars recta tubules in the medullary rays after 6 h, a time when all enzymes studied showed widespread decreased activity throughout the proximal tubule. After 24 h, the pars convoluta appeared morphologically normal but the pars recta was necrotic and exhibited calcification, whereas enzyme activity was decreased (absent in some cases) in both pars convoluta and pars recta. These results support the hypothesis that Hg++, when given in a sublethal dose, is associated with early histochemical changes in the brush border of the proximal tubule, which may be related to early changes in sodium reabsorption and to the subsequent development of acute renal failure. The observation that changes in plasma membrane-associated enzymes occur early and prior to alterations in enzymes of mitochondria and the endoplasmic reticulum suggests that Hg++ interacts initially with the plasma membrane.", "contents": "Studies on the pathophysiology of acute renal failure. II. A histochemical study of the proximal tubule of the rat following administration of mercuric chloride. Acute renal failure was induced in male rats by the subcutaneous injectioon of 4 mg HgC12 per kg body weight. Enzyme activities of the proximal tubule were studied histochemically at six time intervals from 15 min to 24 h. The enzyme studied were alkaline phosphatase, 5'-nucleotidase, acid phosphatase, alpha-glycerophosphate dehydrogenase (NAD-independent), malic dehydrogenase, succinic dehydrogenase, latic dehydrogenase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase. Decreases in activity were observed for alkaline phosphatase and 5'-nucleotidase after 15 min. Acid phosphatase was decreased after 30 min. These three enzymes returned to control levels after 3 h, but malic dehydrogenase and alpha-glycerophosphate dehydrogenase were decreased at this time interval. Succinic dehydrogenase was first decreased after 6 h. The earliest morphological changes detectable by light microscopy were observed in pars recta tubules in the medullary rays after 6 h, a time when all enzymes studied showed widespread decreased activity throughout the proximal tubule. After 24 h, the pars convoluta appeared morphologically normal but the pars recta was necrotic and exhibited calcification, whereas enzyme activity was decreased (absent in some cases) in both pars convoluta and pars recta. These results support the hypothesis that Hg++, when given in a sublethal dose, is associated with early histochemical changes in the brush border of the proximal tubule, which may be related to early changes in sodium reabsorption and to the subsequent development of acute renal failure. The observation that changes in plasma membrane-associated enzymes occur early and prior to alterations in enzymes of mitochondria and the endoplasmic reticulum suggests that Hg++ interacts initially with the plasma membrane."}
{"id": "PMID:188228", "title": "The immunolocalization of ACTH and alpha MSH in human and rat pituitaries.", "content": "Human and rat pituitaries were investigated immunohistochemically for ACTH and alpha MSH activity by means of the enzyme-labeling technique. In rat pituitaries cells present in both the anterior and intermediate lobes were reactive with the anti-ACTH antibodies, the cells from the intermediate lobe were also reactive with anti-alpha MSH antibodies. In human pituitaries, ACTH-immunoreactivity was found in cells from the anterior lobe and cells invading the posterior lobe. In 5 out of 15 pituitaries ACTH-immunoreactive cells located at or invading the posterior lobe were also reactive with the anti-alpha MSH antibodies. It is concluded that the human pituitary cells that invade the posterior lobe represent a population which is at least immunohistochemically identical with the intermediate lobe cells of the rat. The ACTH-immunoreactivity of intermediate lobe cells may be explained by the presence of a corticotropin-like intermediate lobe peptide (CLIP) which has been suggested to be a prohormonal fragment of alpha MSH.", "contents": "The immunolocalization of ACTH and alpha MSH in human and rat pituitaries. Human and rat pituitaries were investigated immunohistochemically for ACTH and alpha MSH activity by means of the enzyme-labeling technique. In rat pituitaries cells present in both the anterior and intermediate lobes were reactive with the anti-ACTH antibodies, the cells from the intermediate lobe were also reactive with anti-alpha MSH antibodies. In human pituitaries, ACTH-immunoreactivity was found in cells from the anterior lobe and cells invading the posterior lobe. In 5 out of 15 pituitaries ACTH-immunoreactive cells located at or invading the posterior lobe were also reactive with the anti-alpha MSH antibodies. It is concluded that the human pituitary cells that invade the posterior lobe represent a population which is at least immunohistochemically identical with the intermediate lobe cells of the rat. The ACTH-immunoreactivity of intermediate lobe cells may be explained by the presence of a corticotropin-like intermediate lobe peptide (CLIP) which has been suggested to be a prohormonal fragment of alpha MSH."}
{"id": "PMID:188229", "title": "Ionophore A23187 and dibutyryl cyclic AMP effects on cell shape and morphology of B-16 melanoma.", "content": "Melanoma cells treated with dibutyryl cyclic AMP (db cAMP) for 24 h resulted in dendritic cells possessing parallel assembled microtubules. A23187 treatments resulted in a biphasic response: Long term effects of the ionophore were characterized by small epitheloid cells while the immediate response produced elongated cells with parallel arranged 10 nm microgilaments, characteristic of dispersive melanocytes.", "contents": "Ionophore A23187 and dibutyryl cyclic AMP effects on cell shape and morphology of B-16 melanoma. Melanoma cells treated with dibutyryl cyclic AMP (db cAMP) for 24 h resulted in dendritic cells possessing parallel assembled microtubules. A23187 treatments resulted in a biphasic response: Long term effects of the ionophore were characterized by small epitheloid cells while the immediate response produced elongated cells with parallel arranged 10 nm microgilaments, characteristic of dispersive melanocytes."}
{"id": "PMID:188230", "title": "Cell surface antigens induced by herpes simplex virus (HSV).", "content": "Among the antigens induced by HSV on the surface of infected cells there are antigens binding anti-HSV antibodies by their combining (Fab) site (HSV-Ag), and others binding antibodies of various specificities, probably through their Fc fragment (IgR). HSV-Ag were demonstrated by cytotoxicity and mixed agglutination tests; IgR were made evident by passive hemadsorption. The ability to induce IgR is especially characteristic of HSV-1 strains, being absent or limited with HSV-2 strains. IgR were not detected on the surface of cells infected by other viruses, such as poliovirus 1, adenovirus 3, measles or vaccinia virus or by viruses belonging to the herpes group (e.g. cytomegalovirus and pseudorabies virus). The ability of bovine infectious rhinotracheitis virus to induce IgR was only slightly expressed. The practical implications of both HSV-Ag and IgR for the techniques aimed at detecting antigens induced by HSV on the surface of infected cells are further discussed.", "contents": "Cell surface antigens induced by herpes simplex virus (HSV). Among the antigens induced by HSV on the surface of infected cells there are antigens binding anti-HSV antibodies by their combining (Fab) site (HSV-Ag), and others binding antibodies of various specificities, probably through their Fc fragment (IgR). HSV-Ag were demonstrated by cytotoxicity and mixed agglutination tests; IgR were made evident by passive hemadsorption. The ability to induce IgR is especially characteristic of HSV-1 strains, being absent or limited with HSV-2 strains. IgR were not detected on the surface of cells infected by other viruses, such as poliovirus 1, adenovirus 3, measles or vaccinia virus or by viruses belonging to the herpes group (e.g. cytomegalovirus and pseudorabies virus). The ability of bovine infectious rhinotracheitis virus to induce IgR was only slightly expressed. The practical implications of both HSV-Ag and IgR for the techniques aimed at detecting antigens induced by HSV on the surface of infected cells are further discussed."}
{"id": "PMID:188231", "title": "Interaction between ceruloplasmin and Sendai virus envelope components. Note III. Separation of Sendai virus envelope components by affinity chromatography.", "content": "Sendai virus envelopes solubilized by Triton X-100 at an alkaline pH were submitted to affinity chromatography on fetuin-Sepharose 4B. In the absence of Triton three groups of envelope fragments were eluted, while in the presence of detergent only two groups were separated. In both cases, envelope fragment populations eluted at low temperature contained hemagglutinin (HA), neuraminidase (N-ase) and HI-antibody blocking (HIb) activity. The populations eluted at 37 degrees C contained N-ase and HIb activity, but no HA. The populations isolated show various ratios of HA, N-ase and HIb, and have different affinities for the coupled fetuin and formolated RBC. Our data strongly suggest that binding to coupled fetuin takes place via enzymatic centres, while binding to RBC occurs via hemagglutinating centres.", "contents": "Interaction between ceruloplasmin and Sendai virus envelope components. Note III. Separation of Sendai virus envelope components by affinity chromatography. Sendai virus envelopes solubilized by Triton X-100 at an alkaline pH were submitted to affinity chromatography on fetuin-Sepharose 4B. In the absence of Triton three groups of envelope fragments were eluted, while in the presence of detergent only two groups were separated. In both cases, envelope fragment populations eluted at low temperature contained hemagglutinin (HA), neuraminidase (N-ase) and HI-antibody blocking (HIb) activity. The populations eluted at 37 degrees C contained N-ase and HIb activity, but no HA. The populations isolated show various ratios of HA, N-ase and HIb, and have different affinities for the coupled fetuin and formolated RBC. Our data strongly suggest that binding to coupled fetuin takes place via enzymatic centres, while binding to RBC occurs via hemagglutinating centres."}
{"id": "PMID:188232", "title": "Photodynamic effect of toluidine blue on MM virus.", "content": "The photodynamic effect of toluidine blue (TB) was studied on MM virus cultivated in L cells and on the RNA extracted form MM virus inoculated to mice by intracerebral route. MM virus infectivity is completely inhibited by the photodynamic action of TB, due to lesions at the molecular level of the viral RNA.", "contents": "Photodynamic effect of toluidine blue on MM virus. The photodynamic effect of toluidine blue (TB) was studied on MM virus cultivated in L cells and on the RNA extracted form MM virus inoculated to mice by intracerebral route. MM virus infectivity is completely inhibited by the photodynamic action of TB, due to lesions at the molecular level of the viral RNA."}
{"id": "PMID:188233", "title": "Further immunological evidence for the presence of Fc receptors on the surface of HSV-infected cells.", "content": "By coupling passive hemadsorption (PHads) reaction with a complement-mediated cytotoxicity test (CT) it is possible to detect the presence on the surface of hamster embryo fibroblasts of Forssman antigens, hindering the demonstration by PHads of the receptors for the Fc-fragment of immunoglobulins (FcR), possibly induced by herpes simplex virus (HSV). These antigens are acetone- and formol-resistant, but they are destroyed by treatment with methanol or ethanol. However, CT with anti-sheep RBC serum performed in HSV-infected monkey kidney cells is always negative, which proves that the attachment of immunoglobulins to these cells occurs exclusively through their Fc-fragments.", "contents": "Further immunological evidence for the presence of Fc receptors on the surface of HSV-infected cells. By coupling passive hemadsorption (PHads) reaction with a complement-mediated cytotoxicity test (CT) it is possible to detect the presence on the surface of hamster embryo fibroblasts of Forssman antigens, hindering the demonstration by PHads of the receptors for the Fc-fragment of immunoglobulins (FcR), possibly induced by herpes simplex virus (HSV). These antigens are acetone- and formol-resistant, but they are destroyed by treatment with methanol or ethanol. However, CT with anti-sheep RBC serum performed in HSV-infected monkey kidney cells is always negative, which proves that the attachment of immunoglobulins to these cells occurs exclusively through their Fc-fragments."}
{"id": "PMID:188234", "title": "Immunoelectrophoretic characterization of Sendai virus antigens.", "content": "Antigens extracted from Sendai virus by solubilization with Triton X-100 (Tx). Tween-20 (Tw) or Triton X-100 and SDS (Tx-SDS) were analysed by rocket, crossed and tandem immunoelectrophoresis. The migration of these antigens through 1% agarose supplemented with guinea pig anti-viral envelope protein anti-serum shows that Tx and Tw antigens consist of three fractions differing in their quantitative ratios, while Tx-SDS exhibits five different fractions. The method proved to be useful for the identification of anti-host antibodies in immune antisera by means of an antigen extracted from the chorio-allantoic membrane of embryonated hen eggs.", "contents": "Immunoelectrophoretic characterization of Sendai virus antigens. Antigens extracted from Sendai virus by solubilization with Triton X-100 (Tx). Tween-20 (Tw) or Triton X-100 and SDS (Tx-SDS) were analysed by rocket, crossed and tandem immunoelectrophoresis. The migration of these antigens through 1% agarose supplemented with guinea pig anti-viral envelope protein anti-serum shows that Tx and Tw antigens consist of three fractions differing in their quantitative ratios, while Tx-SDS exhibits five different fractions. The method proved to be useful for the identification of anti-host antibodies in immune antisera by means of an antigen extracted from the chorio-allantoic membrane of embryonated hen eggs."}
{"id": "PMID:188248", "title": "[Epithelial tumors of the liver (histology, histogenesis, classification)].", "content": "Under study were 120 epithelial hepatic tumors. The problems of histology, histogenesis, classification, morphogenesis of hepatic tumors are being under consideration from the point of view of modern oncology with due account of tumor progression and its development in tumor field. Various trends of differentiation with isolation of histologic variants of epithelial tumors of the liver have been shown. The histological classification is suggested.", "contents": "[Epithelial tumors of the liver (histology, histogenesis, classification)]. Under study were 120 epithelial hepatic tumors. The problems of histology, histogenesis, classification, morphogenesis of hepatic tumors are being under consideration from the point of view of modern oncology with due account of tumor progression and its development in tumor field. Various trends of differentiation with isolation of histologic variants of epithelial tumors of the liver have been shown. The histological classification is suggested."}
{"id": "PMID:188249", "title": "[Polyadenylic acid rich RNA fractions in primary hepatomas induced with diethylnitrosamine].", "content": "The column chromatography with unmodified cellulose revealed a polyadenilic acid rich fraction of total RNA from diethylnitrosamine induced primary hepatomas and normal rat liver. It was shown that the quantity of this fraction was increased to 3.15 per cent. The 2.5% polyacrylamide gel electrophoresis of the polyadenylic acid rich fraction indicated its different spectra in tumors and normal rat liver, the main change being in bipolymer fractions with sedimentation coefficient 28 S and higher.", "contents": "[Polyadenylic acid rich RNA fractions in primary hepatomas induced with diethylnitrosamine]. The column chromatography with unmodified cellulose revealed a polyadenilic acid rich fraction of total RNA from diethylnitrosamine induced primary hepatomas and normal rat liver. It was shown that the quantity of this fraction was increased to 3.15 per cent. The 2.5% polyacrylamide gel electrophoresis of the polyadenylic acid rich fraction indicated its different spectra in tumors and normal rat liver, the main change being in bipolymer fractions with sedimentation coefficient 28 S and higher."}
{"id": "PMID:188251", "title": "[Synthesis of virus-specific RNA under conditions of homologous and heterologous interference by Newcastle disease virus].", "content": "Homologous and heterologous interference by Newcastle disease virus (NDV) was manifested in a marked inhibition of virus-specific RNA synthesis of both the interacting viruses. Inactivation of the interfering NDV by irradiation reduced its capacity to inhibit the synthesis of virus-specific RNA of the homologous virus, leaving its effect on the synthesis of RNA of the heterologous virus unchanged. In contrast, treatment of cell cultures with heparin leading to reduced interferon production eliminated the heterologous interference but did not affect the homologous interference.", "contents": "[Synthesis of virus-specific RNA under conditions of homologous and heterologous interference by Newcastle disease virus]. Homologous and heterologous interference by Newcastle disease virus (NDV) was manifested in a marked inhibition of virus-specific RNA synthesis of both the interacting viruses. Inactivation of the interfering NDV by irradiation reduced its capacity to inhibit the synthesis of virus-specific RNA of the homologous virus, leaving its effect on the synthesis of RNA of the heterologous virus unchanged. In contrast, treatment of cell cultures with heparin leading to reduced interferon production eliminated the heterologous interference but did not affect the homologous interference."}
{"id": "PMID:188250", "title": "[Abortive myxovirus infection in Ehrlich ascites carcinoma cells. Production of heterokaryons in permissive cells and analysis of virus-specific structures].", "content": "Hybridization of Ehrlich ascitic carcinoma cells and chicken fibroblasts using UV-inactivated Sendai virus produced the following variants of homo- and heterokaryons: (a) uninfected Ehrlich cells, (b) fowl plague virus-infected chicken fibroblasts, (c) uninfected Ehrlich cells and uninfected chicken fibroblasts; (d) infected Ehrlich cells and infected chicken fibroblasts, (e) infected Ehrlich cells and uninfected chicken fibroblasts. The analysis of the material produced by heterokaryons gave the following results: when Ehrlich ascitic carcinoma cells infected with classical fowl plaque virus and labeled with 3H-uridine fused with uninfected unlabeled chicken fibroblasts, the heterokaryons, in addition to structures with the buoyant density of 1.29 g/ml typical for infected cells, also produced virus structures with a density of 1.25 g/ml and had a higher infectious activity (5.2 X 10(7) PFU/ml) than the structures produced by infected Ehrlich cells (5.8 X 10(6) PFU/ml); after fusion of Ehrlich ascitic carcinoma cells infected with fowl plague virus and labelled with 3H-uridine with unlabelled chicken fibroblasts infected with fowl plague virus heterokaryons produced virus structures with densities of 1.29 g/ml and 1.22 g/ml which had even higher infectious activity (8.6 X 10(8) PFU/ml) than the structures produced by infected Ehlrich ascitic cells.", "contents": "[Abortive myxovirus infection in Ehrlich ascites carcinoma cells. Production of heterokaryons in permissive cells and analysis of virus-specific structures]. Hybridization of Ehrlich ascitic carcinoma cells and chicken fibroblasts using UV-inactivated Sendai virus produced the following variants of homo- and heterokaryons: (a) uninfected Ehrlich cells, (b) fowl plague virus-infected chicken fibroblasts, (c) uninfected Ehrlich cells and uninfected chicken fibroblasts; (d) infected Ehrlich cells and infected chicken fibroblasts, (e) infected Ehrlich cells and uninfected chicken fibroblasts. The analysis of the material produced by heterokaryons gave the following results: when Ehrlich ascitic carcinoma cells infected with classical fowl plaque virus and labeled with 3H-uridine fused with uninfected unlabeled chicken fibroblasts, the heterokaryons, in addition to structures with the buoyant density of 1.29 g/ml typical for infected cells, also produced virus structures with a density of 1.25 g/ml and had a higher infectious activity (5.2 X 10(7) PFU/ml) than the structures produced by infected Ehrlich cells (5.8 X 10(6) PFU/ml); after fusion of Ehrlich ascitic carcinoma cells infected with fowl plague virus and labelled with 3H-uridine with unlabelled chicken fibroblasts infected with fowl plague virus heterokaryons produced virus structures with densities of 1.29 g/ml and 1.22 g/ml which had even higher infectious activity (8.6 X 10(8) PFU/ml) than the structures produced by infected Ehlrich ascitic cells."}
{"id": "PMID:188252", "title": "[Study of LPV oncornavirus reproduction in mixed cell culture].", "content": "Electron microscopy and mathematical analysis were used to determine the intensity of LPV oncornavirus production by a single cell in co-cultivated human diploid cells and cells of the continuous T-9 line. Maximum production of intracytoplasmic particles of A type was observed at 48 hours of cultivation, and extracellular virions at 96 hours. Mature virions of B type were more numerous than mature virions of C type in the mixed culture. On the whole the amolnt of mature virions was greater than that of immature ones, and the amount of intracytoplasmic A type particles was considerably greater than that of extracellular particles. By the total amount of production of all virus-specific structures and the two-wave pattern of virus production this mixed culture passaged at a ratio of HDC to T-9 cells 2000 : 1 resembled a culture of T-9 line. Thus, this study indicates that the infected HDC culture at later intervals of cultivation (96 hours) is a more active \"producer\" of LPV oncornavirus than the main line of T-9 cells or mixed HDC--T-9 culture.", "contents": "[Study of LPV oncornavirus reproduction in mixed cell culture]. Electron microscopy and mathematical analysis were used to determine the intensity of LPV oncornavirus production by a single cell in co-cultivated human diploid cells and cells of the continuous T-9 line. Maximum production of intracytoplasmic particles of A type was observed at 48 hours of cultivation, and extracellular virions at 96 hours. Mature virions of B type were more numerous than mature virions of C type in the mixed culture. On the whole the amolnt of mature virions was greater than that of immature ones, and the amount of intracytoplasmic A type particles was considerably greater than that of extracellular particles. By the total amount of production of all virus-specific structures and the two-wave pattern of virus production this mixed culture passaged at a ratio of HDC to T-9 cells 2000 : 1 resembled a culture of T-9 line. Thus, this study indicates that the infected HDC culture at later intervals of cultivation (96 hours) is a more active \"producer\" of LPV oncornavirus than the main line of T-9 cells or mixed HDC--T-9 culture."}
{"id": "PMID:188253", "title": "[Production of J-96 cell culture chronically infected with herpes simplex virus and study of some of its properties].", "content": "Comparative effectiveness of various methods for production of chronic infection with herpes simplex virus (HSV) in J-96 cell culture: inclusion into the culture fluid of the infected cultures of immune serum to herpes virus, immune serum to HSV-infected J-96 cells and frequent changes of the medium, is described. The advantage of the second method has been found. The chronically infected culture was resistant to superinfection with the homologous virus. In passages, when the chronically infected culture produced no active infectious virus, the portion of cells containing the virus antigen was 0.8%. In this culture interferon was found in a low titer. Morphological and histochemical studies also indicated some changes in chronically infected cultures as compared with the controls, namely, an increase in the number of spindle-shaped elements, thickening of the nuclear membrane, an increase in the DNA concentration. The culture has been designated JH and is in the 220th passage now.", "contents": "[Production of J-96 cell culture chronically infected with herpes simplex virus and study of some of its properties]. Comparative effectiveness of various methods for production of chronic infection with herpes simplex virus (HSV) in J-96 cell culture: inclusion into the culture fluid of the infected cultures of immune serum to herpes virus, immune serum to HSV-infected J-96 cells and frequent changes of the medium, is described. The advantage of the second method has been found. The chronically infected culture was resistant to superinfection with the homologous virus. In passages, when the chronically infected culture produced no active infectious virus, the portion of cells containing the virus antigen was 0.8%. In this culture interferon was found in a low titer. Morphological and histochemical studies also indicated some changes in chronically infected cultures as compared with the controls, namely, an increase in the number of spindle-shaped elements, thickening of the nuclear membrane, an increase in the DNA concentration. The culture has been designated JH and is in the 220th passage now."}
{"id": "PMID:188254", "title": "[Study of experimental chronic infection in mice caused by herpes simplex virus].", "content": "A chronic herpetic infection was produced in white random-bred mice by intradermal inoculation with the L2, 333 and K strains. The virus was regularly detected in the blood of the animals by the method of co-cultivation of leukocytes and human embryo fibroblasts for 70 days (the observation period). The virus was isolated from the brain, the spinal cord and viscera from the 3rd till the 30th postinoculation day. The virus antigen was found in leukocytes, and erythrocytes of the blood, the spinal cord and the brain from the 7th till the 70th day, and in the liver and spleen from the 7th to the 30th day. The titer of interferon in the viscera and serum of mice in the first 2-3 days after inoculation was 8 units, and subsequently 2 units. The interferon-producing activity of the blood leukocytes in mice was reduced (16-32 units) as compared to that in uninfected animals (64-128 units). The antibody titer at 7 days after incoulation was 1 : 32 in the blood serum of mice, at later intervals no antibody was found. Inflammatory and dengerative changes in the central nervous system and viscera of mice were detected throughout the observation period starting from the 7th day postinoculation.", "contents": "[Study of experimental chronic infection in mice caused by herpes simplex virus]. A chronic herpetic infection was produced in white random-bred mice by intradermal inoculation with the L2, 333 and K strains. The virus was regularly detected in the blood of the animals by the method of co-cultivation of leukocytes and human embryo fibroblasts for 70 days (the observation period). The virus was isolated from the brain, the spinal cord and viscera from the 3rd till the 30th postinoculation day. The virus antigen was found in leukocytes, and erythrocytes of the blood, the spinal cord and the brain from the 7th till the 70th day, and in the liver and spleen from the 7th to the 30th day. The titer of interferon in the viscera and serum of mice in the first 2-3 days after inoculation was 8 units, and subsequently 2 units. The interferon-producing activity of the blood leukocytes in mice was reduced (16-32 units) as compared to that in uninfected animals (64-128 units). The antibody titer at 7 days after incoulation was 1 : 32 in the blood serum of mice, at later intervals no antibody was found. Inflammatory and dengerative changes in the central nervous system and viscera of mice were detected throughout the observation period starting from the 7th day postinoculation."}
{"id": "PMID:188260", "title": "[Clinical picture and prognosis of insulinoma].", "content": "A case of insulinoma is reported, with initial malignant degeneration, diagnosed and operated 16 years ago. Six years later hypoglycemic attacks appeared again and lymph metastasis from malignant degenerated insulinoma were found near to the pancreas. After a period of eight years, in good health state, a third surgical operation was performed because of repeated hypoglycemic attacks and a new metastasis from the insulinoma was found in the pancreas tail. The patient has no hypoglycemic phenomena 18 months after the last operation. Besides that long-period of progress of the malignant degenerated insulinoma, not observed so far, certain peculiarities of the carbohydrate metabolism of the patient are stressed upon, as well as the necessity of early diagnosis and timely surgical treatment of insulinoma.", "contents": "[Clinical picture and prognosis of insulinoma]. A case of insulinoma is reported, with initial malignant degeneration, diagnosed and operated 16 years ago. Six years later hypoglycemic attacks appeared again and lymph metastasis from malignant degenerated insulinoma were found near to the pancreas. After a period of eight years, in good health state, a third surgical operation was performed because of repeated hypoglycemic attacks and a new metastasis from the insulinoma was found in the pancreas tail. The patient has no hypoglycemic phenomena 18 months after the last operation. Besides that long-period of progress of the malignant degenerated insulinoma, not observed so far, certain peculiarities of the carbohydrate metabolism of the patient are stressed upon, as well as the necessity of early diagnosis and timely surgical treatment of insulinoma."}
{"id": "PMID:188255", "title": "[Expression of individual proteins of mouse mammary gland cancer virus in tumors in mice of various strains].", "content": "Expression of the main structural proteins of mammary gland cancer virus, gp52 and p27, was studied with the immune sera to these proteins in homogenates of tumors from mice of low and high cancer lines. Protein gp52 was found only in tumors of mice-carriers of MTV-S. In a fraction of purified type A particles from the cytoplasm of mammary gland cancer no gp52 was found, but with the antiserum to p27 this fraction reacted by a line identical to that with the antigen from C2HF mouse tumor.", "contents": "[Expression of individual proteins of mouse mammary gland cancer virus in tumors in mice of various strains]. Expression of the main structural proteins of mammary gland cancer virus, gp52 and p27, was studied with the immune sera to these proteins in homogenates of tumors from mice of low and high cancer lines. Protein gp52 was found only in tumors of mice-carriers of MTV-S. In a fraction of purified type A particles from the cytoplasm of mammary gland cancer no gp52 was found, but with the antiserum to p27 this fraction reacted by a line identical to that with the antigen from C2HF mouse tumor."}
{"id": "PMID:188261", "title": "[Several functional changes in the  livers of patients with diabetes mellitus].", "content": "The authors have studied the functional liver state in 107 patients with diabetes mellitus. Various stages of functional liver disturbances were found in a considerable part of them. With a few exceptions, the latter have the highest incidence and severity among the patients with decompensated, with mixed type diabetes and with remote vascular degenerative manifestations. Radioisotope investigations with 131J-Bengal pink, reveals the earliest developed changes in some of the liver functions, as compared with rest of the tests. The functional liver state is recommended to be determined in all diabetics with a view to an early detection of the developed functional disturbances and their timely treatment.", "contents": "[Several functional changes in the  livers of patients with diabetes mellitus]. The authors have studied the functional liver state in 107 patients with diabetes mellitus. Various stages of functional liver disturbances were found in a considerable part of them. With a few exceptions, the latter have the highest incidence and severity among the patients with decompensated, with mixed type diabetes and with remote vascular degenerative manifestations. Radioisotope investigations with 131J-Bengal pink, reveals the earliest developed changes in some of the liver functions, as compared with rest of the tests. The functional liver state is recommended to be determined in all diabetics with a view to an early detection of the developed functional disturbances and their timely treatment."}
{"id": "PMID:188256", "title": "[Development and study of an experimental herpesvirus vaccine].", "content": "The strains suitable for the development of herpesvirus vaccine were selected as a result of studies on numerous herpes virus strains isolated from patients with relapsing herpes infection of various localizations. Infectious tissue culture antigens were obtained by roller cultivation of chick embryo fibroblast cultures infected with herpesvirus in the presence of 0.2% human serum albumin. A high immunogenic and antigenic activity of the experimental vaccines prepared from these antigens was established. Animal experiments demonstrated the possibility of control of the specific activity of herpesvirus vaccines.", "contents": "[Development and study of an experimental herpesvirus vaccine]. The strains suitable for the development of herpesvirus vaccine were selected as a result of studies on numerous herpes virus strains isolated from patients with relapsing herpes infection of various localizations. Infectious tissue culture antigens were obtained by roller cultivation of chick embryo fibroblast cultures infected with herpesvirus in the presence of 0.2% human serum albumin. A high immunogenic and antigenic activity of the experimental vaccines prepared from these antigens was established. Animal experiments demonstrated the possibility of control of the specific activity of herpesvirus vaccines."}
{"id": "PMID:188257", "title": "[Isolation and study of biophysical properties of oncornaviruses type A and C minimal forms].", "content": "The method of differential centrifugation was used for concentration and purification of the minimal form of oncornaviruses type A and C. The structures showed heterogeneous distribution in sucrose density gradient and formed a peak in the zone of 1.135 g/ml. Electron microscope examinations of negatively stained preparations showed that the size of the minimal forms of oncornaviruses type A and C was 25-60 nm, the diameter of nucleoids 10-30 nm.", "contents": "[Isolation and study of biophysical properties of oncornaviruses type A and C minimal forms]. The method of differential centrifugation was used for concentration and purification of the minimal form of oncornaviruses type A and C. The structures showed heterogeneous distribution in sucrose density gradient and formed a peak in the zone of 1.135 g/ml. Electron microscope examinations of negatively stained preparations showed that the size of the minimal forms of oncornaviruses type A and C was 25-60 nm, the diameter of nucleoids 10-30 nm."}
{"id": "PMID:188262", "title": "[Determination of free and protein bound cortisol, transcortin binding capacity and adrenocorticotropic hormone in the plasma of patients with hypertension].", "content": "The total non-conjugated plasma cortisol in 60 patients with hypertension disease (HD)is 17.5 mkg/ml. The free non-conjugated cortisol represents 8.45 per cent of the total - 1,5 mkg%, considerably (p less than 0.0001) higher than that in healthy subjects. Protein conjugated cortisol is 16.0 mkg%. The bounding capacity of transcortin the plasma of hypertonics is considerably decreased (p less than 0.0001) - 15.8 mkg (in healthy - 18.5 mkg) per 100 ml. ACTH level in the plasma of patients with HD is 32.0 pg/ml, considerably higher than that in healthy (25.8 pg/ml, p less than 0.0001). The elevation of the biologically active cortisol fraction in plasma of hypertonics is a function both of hypothalamo-hypopheseal stimulation and of transcortin level. That latent hypercortisolism is admitted to be manifestation of hypothalamo - hypopheseal superstimulation by increased ACTH secretion, in case of confirmed cerebro-hypothalamic disturbances in patients with hypertension disease.", "contents": "[Determination of free and protein bound cortisol, transcortin binding capacity and adrenocorticotropic hormone in the plasma of patients with hypertension]. The total non-conjugated plasma cortisol in 60 patients with hypertension disease (HD)is 17.5 mkg/ml. The free non-conjugated cortisol represents 8.45 per cent of the total - 1,5 mkg%, considerably (p less than 0.0001) higher than that in healthy subjects. Protein conjugated cortisol is 16.0 mkg%. The bounding capacity of transcortin the plasma of hypertonics is considerably decreased (p less than 0.0001) - 15.8 mkg (in healthy - 18.5 mkg) per 100 ml. ACTH level in the plasma of patients with HD is 32.0 pg/ml, considerably higher than that in healthy (25.8 pg/ml, p less than 0.0001). The elevation of the biologically active cortisol fraction in plasma of hypertonics is a function both of hypothalamo-hypopheseal stimulation and of transcortin level. That latent hypercortisolism is admitted to be manifestation of hypothalamo - hypopheseal superstimulation by increased ACTH secretion, in case of confirmed cerebro-hypothalamic disturbances in patients with hypertension disease."}
{"id": "PMID:188259", "title": "[Determination of viremia in patients with para-influenza by immunofluorescence technic].", "content": "Viremia in parainfluenza was studied in 80 patients (35 children and 45 adults) in the time course of the disease during the springautumn period of 1969-1974. For the detection of viremia, the immunofluorescence procedure, namely, the detection of early stages of virus replication in the tissue culture cells infected with the blood from the patients, was used. The tests were performed with 204 blood specimens. The blood clot was diluted 1 : 1 with distilled water and followed the conventional method. Commercial FITZ-globulins with high antibody titres to parainfluenza virus type 1, 2, and 3, influenza A2 and B and adenovirus types 3 and 7, were used. The clinical manifestations of parainfluenza in the observed patients were typical of the disease. Complications developed in 60% of the cases. As a result of clinical and laboratory examinations, viremed early and late (up to 22 days) in the disease in patients of different age groups both at high and low fever; for longer periods and later in the disease it was observed in patients with complications (pneumonia, maxillary simusitis), but always in the presence of clinical manifestations of parainfluenza.", "contents": "[Determination of viremia in patients with para-influenza by immunofluorescence technic]. Viremia in parainfluenza was studied in 80 patients (35 children and 45 adults) in the time course of the disease during the springautumn period of 1969-1974. For the detection of viremia, the immunofluorescence procedure, namely, the detection of early stages of virus replication in the tissue culture cells infected with the blood from the patients, was used. The tests were performed with 204 blood specimens. The blood clot was diluted 1 : 1 with distilled water and followed the conventional method. Commercial FITZ-globulins with high antibody titres to parainfluenza virus type 1, 2, and 3, influenza A2 and B and adenovirus types 3 and 7, were used. The clinical manifestations of parainfluenza in the observed patients were typical of the disease. Complications developed in 60% of the cases. As a result of clinical and laboratory examinations, viremed early and late (up to 22 days) in the disease in patients of different age groups both at high and low fever; for longer periods and later in the disease it was observed in patients with complications (pneumonia, maxillary simusitis), but always in the presence of clinical manifestations of parainfluenza."}
{"id": "PMID:188258", "title": "[Results of serologic surveys of children with acute stenosing laryngotracheobronchitis].", "content": "The materials of serologic surveys of 269 children with acute stenosing laryngotracheobronchitis hospitalized in Children's Infectious Hospital No. 3, Leningrad, are presented. Acute stenosing laryngotracheobronchitis developed most frequently against the background of low titres of antibody to viruses of the respiratory group. Severe cases of the disease were caused by influenza A2 virus, milder cases by influenza B, parainfluenza, respiratory syncytial and adenoviruses.", "contents": "[Results of serologic surveys of children with acute stenosing laryngotracheobronchitis]. The materials of serologic surveys of 269 children with acute stenosing laryngotracheobronchitis hospitalized in Children's Infectious Hospital No. 3, Leningrad, are presented. Acute stenosing laryngotracheobronchitis developed most frequently against the background of low titres of antibody to viruses of the respiratory group. Severe cases of the disease were caused by influenza A2 virus, milder cases by influenza B, parainfluenza, respiratory syncytial and adenoviruses."}
{"id": "PMID:188265", "title": "[Bacteriological, virological, and mycological check-up in patients on regular dialysis treatment and after renal transplantation (author's transl)].", "content": "Regular bacteriological control examinations of the dialysate may contribue to the elimination of pyrogenic and even septic reactions. Regular checks of HBS-Ag and HBS-Ab are an effective measure in the early diagnosis of hepatitis B, which is characteristically anicteric and follows a prolonged course in patients on regular dialysis treatment (RDT). Virological examinations can be helpful in the diagnosis of cytomegalovirus (CMV) disease in certain cases of unexplained fever. Regular bacteriological examination of the urine is important in the detection of a urinary tract infection possibly necessitating binephrectomy prior to transplantation. After renal transplantation bacteriological control examinations of the urine, determinations of HBS-Ag and HBS-Ab, complement-binding reactions to CMV and mycotic cultures from the throat, sputum and urine should be regularly performed. Urinary tract infections may be found in up to 88% of the transplanted patients. Hepatits-B infection was noted in 62.8% of this case material. Positive Candida albicans cultures from samples of the uurine usually indicate systemic Candida albicans infection. The described diagnostic measures contribute to an effective prophylaxis and therapy of infective complications in patients on RDT and after renal transplantation.", "contents": "[Bacteriological, virological, and mycological check-up in patients on regular dialysis treatment and after renal transplantation (author's transl)]. Regular bacteriological control examinations of the dialysate may contribue to the elimination of pyrogenic and even septic reactions. Regular checks of HBS-Ag and HBS-Ab are an effective measure in the early diagnosis of hepatitis B, which is characteristically anicteric and follows a prolonged course in patients on regular dialysis treatment (RDT). Virological examinations can be helpful in the diagnosis of cytomegalovirus (CMV) disease in certain cases of unexplained fever. Regular bacteriological examination of the urine is important in the detection of a urinary tract infection possibly necessitating binephrectomy prior to transplantation. After renal transplantation bacteriological control examinations of the urine, determinations of HBS-Ag and HBS-Ab, complement-binding reactions to CMV and mycotic cultures from the throat, sputum and urine should be regularly performed. Urinary tract infections may be found in up to 88% of the transplanted patients. Hepatits-B infection was noted in 62.8% of this case material. Positive Candida albicans cultures from samples of the uurine usually indicate systemic Candida albicans infection. The described diagnostic measures contribute to an effective prophylaxis and therapy of infective complications in patients on RDT and after renal transplantation."}
{"id": "PMID:188266", "title": "[Thymic carcinoid. Case report and review of the literature (author's transl)].", "content": "A case of a primary thymic carcinoid tumour of a 32 year old male is reported, and the previously published 25 cases are reviewed. The neoplasms occur in adults, predominantly in males: they are located in the anterior or antero-superior mediastinum. The only sufficient treatment is the surgical excision; through radiotherapy may be indicated in some cases, too. The tumour is characterized by the formation of rosettes, ribbons and garlands; sheet-like or medullary areas, and large clusters with central necrosis. The tumour is positive for the Grimelius argyrophil silver stain. Ultrastructurally numerous dense-core \"neurosecretory\" granules are observed. The formal pathogenesis is similar to that of carcinoid tumours of other locations; particularly of those arriving from derivates of the foregut, respectively from the APUD cell system. At present it cannot be decided whether this particular tumour of the thymus represents an autochthonic thymic carcinoid or simply a teratoma with a differentiation in one direction in the sence of a simplified teratoma.", "contents": "[Thymic carcinoid. Case report and review of the literature (author's transl)]. A case of a primary thymic carcinoid tumour of a 32 year old male is reported, and the previously published 25 cases are reviewed. The neoplasms occur in adults, predominantly in males: they are located in the anterior or antero-superior mediastinum. The only sufficient treatment is the surgical excision; through radiotherapy may be indicated in some cases, too. The tumour is characterized by the formation of rosettes, ribbons and garlands; sheet-like or medullary areas, and large clusters with central necrosis. The tumour is positive for the Grimelius argyrophil silver stain. Ultrastructurally numerous dense-core \"neurosecretory\" granules are observed. The formal pathogenesis is similar to that of carcinoid tumours of other locations; particularly of those arriving from derivates of the foregut, respectively from the APUD cell system. At present it cannot be decided whether this particular tumour of the thymus represents an autochthonic thymic carcinoid or simply a teratoma with a differentiation in one direction in the sence of a simplified teratoma."}
{"id": "PMID:188267", "title": "Hepatitis B virus, cirrhosis and primary carcinoma of the liver. An electron microscopic study.", "content": "The core and coat of hepatitis B virus were found by electron microscopy in parenchymal cells of a liver biopsy from a 61 year old man with chronic active hepatitis and cirrhosis of the liver. Laparoscopy, 35 days after liver biopsy, and autopsy 42 days later confirmed the cirrhosis and showed in addition a well differentiated hepatoma. The possibility of a viral aetiology for the cirrhosis and primary carcinoma of the liver is considered.", "contents": "Hepatitis B virus, cirrhosis and primary carcinoma of the liver. An electron microscopic study. The core and coat of hepatitis B virus were found by electron microscopy in parenchymal cells of a liver biopsy from a 61 year old man with chronic active hepatitis and cirrhosis of the liver. Laparoscopy, 35 days after liver biopsy, and autopsy 42 days later confirmed the cirrhosis and showed in addition a well differentiated hepatoma. The possibility of a viral aetiology for the cirrhosis and primary carcinoma of the liver is considered."}
{"id": "PMID:188270", "title": "[Radiochemical investigations on the decomposition of (mono) methyl-mercury by means of acid with regard to the determination of total mercury in fish (author's transl)].", "content": "Considerable amonts of mercury in fish muscle tissue are organically bound i.e. appear as (mono)methylmercury-compounds. In order to make mercury of organic origin available for the determination of total mercury by the \"cold vapour atomic absorption method\", a splitting of the carbon-mercury bond by means of suitable chemical treatment must be maintained beforehand. The main subject of this article are investigations with special regard to the behaviour of (mono)methylmercurychloride during different wet digestion methods. The procedures under study involve wet digestion under reflux with HNO3, with mixtures of HNO3 and HC10(4) and HNO3 and  H2SO4, as well as wet digestion with HNO3 in a closed system (pressure decomposition). The course of the decomposition of (mono)methylmercury dependent on time, temperature and concentration of reagents are discussed in detail. All experiments were controlled by measurement of the radioactivity of Hg-203 which had been added in the chemical form of CH3-Hg-Cl. From the analytical results obtained two methods of sample preparation have been derived that permit a reliable determination of total mercury in fish.", "contents": "[Radiochemical investigations on the decomposition of (mono) methyl-mercury by means of acid with regard to the determination of total mercury in fish (author's transl)]. Considerable amonts of mercury in fish muscle tissue are organically bound i.e. appear as (mono)methylmercury-compounds. In order to make mercury of organic origin available for the determination of total mercury by the \"cold vapour atomic absorption method\", a splitting of the carbon-mercury bond by means of suitable chemical treatment must be maintained beforehand. The main subject of this article are investigations with special regard to the behaviour of (mono)methylmercurychloride during different wet digestion methods. The procedures under study involve wet digestion under reflux with HNO3, with mixtures of HNO3 and HC10(4) and HNO3 and  H2SO4, as well as wet digestion with HNO3 in a closed system (pressure decomposition). The course of the decomposition of (mono)methylmercury dependent on time, temperature and concentration of reagents are discussed in detail. All experiments were controlled by measurement of the radioactivity of Hg-203 which had been added in the chemical form of CH3-Hg-Cl. From the analytical results obtained two methods of sample preparation have been derived that permit a reliable determination of total mercury in fish."}
{"id": "PMID:188271", "title": "[Resistance to chemotherapy of aerobic bacteria from nonspecific odontogenic infections].", "content": "Germs in patients suffering from nonspecific odontogenous infections described in a previous paper were analysed with regard to their resistance to chemotherapy (1964 to 1971). At the same time it was discovered that in the bacteria groups: staphyloccocus aureus, streptococci and pneumococci and enterobacteriaceae plus pseudomonas (344 strains) their sensitivity to penicillin, streptomycin, chloramphenicol, oxytetracyclin, erythromycin, polymyxin B and nifurantin varied in several and significant ways. Significant changes were established in the resistance of staphylococcus aureus to all the potentially effective antibiotics, while from 1969 to 1971 the strains with the least resistance appeared. In the 1970 to 1971 period strepto- and pneumococci showed insensitivity to penicillin and streptomycin more frequently than before. From 1969 to 1971 entero-bacteriaceae and pseudomonas also showed evidence of increasing loss of sensitivity to chloramphenicol and oxytetracyclin, whereas the frequency of strains resistant to polymyxin B and nifurantine diminished. The findings are being discussed.", "contents": "[Resistance to chemotherapy of aerobic bacteria from nonspecific odontogenic infections]. Germs in patients suffering from nonspecific odontogenous infections described in a previous paper were analysed with regard to their resistance to chemotherapy (1964 to 1971). At the same time it was discovered that in the bacteria groups: staphyloccocus aureus, streptococci and pneumococci and enterobacteriaceae plus pseudomonas (344 strains) their sensitivity to penicillin, streptomycin, chloramphenicol, oxytetracyclin, erythromycin, polymyxin B and nifurantin varied in several and significant ways. Significant changes were established in the resistance of staphylococcus aureus to all the potentially effective antibiotics, while from 1969 to 1971 the strains with the least resistance appeared. In the 1970 to 1971 period strepto- and pneumococci showed insensitivity to penicillin and streptomycin more frequently than before. From 1969 to 1971 entero-bacteriaceae and pseudomonas also showed evidence of increasing loss of sensitivity to chloramphenicol and oxytetracyclin, whereas the frequency of strains resistant to polymyxin B and nifurantine diminished. The findings are being discussed."}
{"id": "PMID:188275", "title": "[Isolation of various structural elements of gram-negative bacteria of the Bordetella genus and a study of their properties. II. Isolation of the cytoplasmic membrane fraction from the protoplasts of B. pertussis and a study of their chemical and enzymatic properties].", "content": "A possibility of obtaining a fraction of cytoplasmic membranes maximally purified of the cell wall material was for the first time shown on a model of Gram negative bacteria (B. pertussis). The results of electron microscopy, chemical analysis for the presence of the cell wall material--hexosamines, and of the activity of the respiratory chain enzymes served as control.", "contents": "[Isolation of various structural elements of gram-negative bacteria of the Bordetella genus and a study of their properties. II. Isolation of the cytoplasmic membrane fraction from the protoplasts of B. pertussis and a study of their chemical and enzymatic properties]. A possibility of obtaining a fraction of cytoplasmic membranes maximally purified of the cell wall material was for the first time shown on a model of Gram negative bacteria (B. pertussis). The results of electron microscopy, chemical analysis for the presence of the cell wall material--hexosamines, and of the activity of the respiratory chain enzymes served as control."}
{"id": "PMID:188276", "title": "[A study of toxic substances in pertussis cultures].", "content": "For the purpose of studying the toxic properties of pertussis strains with different agglutination composition and to ascertain the interrelationship between the action of the toxic substances and the serological type of the strains the author used a test of the weight change in albino mice to which crude and heated (at 56 degrees C for 10 minutes) suspensions of the strains of various serological types were injected intraperitoneally. The toxic properties were checked in 17 strains. The test of the change of the animal body weight with the determination of the regression coefficient permitted to determine roughly the presence of the toxic substances in the strains; the action of the thermostable dermonecrotic toxin and thermostable endotoxin was expressed with greater constancy than that of the lymphocytosis stimulating factor. There was no interrelationship between the manifestation of the action of toxic substances in the pertussis strains and their serological type. The toxic activity peristed in the strains stored in dried condition.", "contents": "[A study of toxic substances in pertussis cultures]. For the purpose of studying the toxic properties of pertussis strains with different agglutination composition and to ascertain the interrelationship between the action of the toxic substances and the serological type of the strains the author used a test of the weight change in albino mice to which crude and heated (at 56 degrees C for 10 minutes) suspensions of the strains of various serological types were injected intraperitoneally. The toxic properties were checked in 17 strains. The test of the change of the animal body weight with the determination of the regression coefficient permitted to determine roughly the presence of the toxic substances in the strains; the action of the thermostable dermonecrotic toxin and thermostable endotoxin was expressed with greater constancy than that of the lymphocytosis stimulating factor. There was no interrelationship between the manifestation of the action of toxic substances in the pertussis strains and their serological type. The toxic activity peristed in the strains stored in dried condition."}
{"id": "PMID:188277", "title": "[Study of leukotoxic activity of Cl. perfringens type A toxin and its fractions obtained by gel filtration and ion exchange chromatography].", "content": "In gel-filtration of Cl. perfringens type A toxin on Sephadex F-100 and F-50 there was revealed relationship between the leukotoxic activity and a high-molecular component. A method of ion-exchange chromatography on a column with DEAE-Sephadex A-25 from the Cl. perfringens toxin there were obtained 8 fractions 3 of which possessed a marked leukotoxic activity: the capacity to destroy neutrophils in the Svejcar and Vancurik test and to-depress the phagocytic activity of leukocytes. Lecithinase and lethal activity was revealed in one of these fractions only. Leukotoxic fractions differed by the capacity to destroy neutrophils and to decrease their phagocytic activity.", "contents": "[Study of leukotoxic activity of Cl. perfringens type A toxin and its fractions obtained by gel filtration and ion exchange chromatography]. In gel-filtration of Cl. perfringens type A toxin on Sephadex F-100 and F-50 there was revealed relationship between the leukotoxic activity and a high-molecular component. A method of ion-exchange chromatography on a column with DEAE-Sephadex A-25 from the Cl. perfringens toxin there were obtained 8 fractions 3 of which possessed a marked leukotoxic activity: the capacity to destroy neutrophils in the Svejcar and Vancurik test and to-depress the phagocytic activity of leukocytes. Lecithinase and lethal activity was revealed in one of these fractions only. Leukotoxic fractions differed by the capacity to destroy neutrophils and to decrease their phagocytic activity."}
{"id": "PMID:188278", "title": "[Study of smallpox vaccine virus distribution in the body of rabbits following oral immunization].", "content": "Virological and immunofluorescent methods were applied to the study of the distribution of the smallpox vaccine virus in the organs and tissues of rabbits immunized orally. It appeared that the vaccinal process developed with a predominant localization of the antigen in the regional (in respect to the site of administration) lymph nodes; the virus was revealed in the cell cytoplasm.", "contents": "[Study of smallpox vaccine virus distribution in the body of rabbits following oral immunization]. Virological and immunofluorescent methods were applied to the study of the distribution of the smallpox vaccine virus in the organs and tissues of rabbits immunized orally. It appeared that the vaccinal process developed with a predominant localization of the antigen in the regional (in respect to the site of administration) lymph nodes; the virus was revealed in the cell cytoplasm."}
{"id": "PMID:188280", "title": "Activities of prostaglandins and prostaglandin endoperoxides at adrenergic neuroeffector junctions.", "content": "The results presented in this paper indicate that: 1. The prostaglandin synthesis inhibitor, indomethacin, increases noradrenaline turnover in a variety of rat organs. This observation increases the probability that prostaglandins are involved in the control of adrenergic neurotransmission in vivo. 2. Administration of endoperoxides inhibits the release of noradrenaline from adrenergic nerve terminals. The effect can be explained, however, at least in part, by formation of degradation products, presumably mainly prostaglandin E2. 3. Prostaglandin F2 alpha enhances smooth muscle responses to adrenergic nerve stimulation in rabbit heart and guinea pig vas deferens. These actions must be considered prostjunctional, since the release of noradrenaline is unchanged or depressed.", "contents": "Activities of prostaglandins and prostaglandin endoperoxides at adrenergic neuroeffector junctions. The results presented in this paper indicate that: 1. The prostaglandin synthesis inhibitor, indomethacin, increases noradrenaline turnover in a variety of rat organs. This observation increases the probability that prostaglandins are involved in the control of adrenergic neurotransmission in vivo. 2. Administration of endoperoxides inhibits the release of noradrenaline from adrenergic nerve terminals. The effect can be explained, however, at least in part, by formation of degradation products, presumably mainly prostaglandin E2. 3. Prostaglandin F2 alpha enhances smooth muscle responses to adrenergic nerve stimulation in rabbit heart and guinea pig vas deferens. These actions must be considered prostjunctional, since the release of noradrenaline is unchanged or depressed."}
{"id": "PMID:188281", "title": "Influence of ethanol oxidation rate on the lactate/pyruvate ratio and phosphorylation state of the liver in fed rats.", "content": "The effect of the ethanol oxidation rate on the interaction between the phosphorylation state (the [ATP]/[ADP] X [HPO4]2- ratio) and the redox state (the free [NAD+]/[NADH] ratio) of the liver cytosol was studied in intact fed rats. The rate of ethanol oxidation was inhibited to different degrees with pyrazole. The ethanol oxidation rate had no influence on the liver lactate level but correlated significantly with the pyruvate level. Accordingly, a significant correlation was also found between the ethanol oxidation rate and the lactate/pyruvate ratio. The rate of ethanol oxidation correlated significantly with the liver 3-phosphoglycerate level. No change in the glyceraldehyde-3-phosphate level was found. No correlation was found between the ethanol oxidation rate and the glyceraldehyde-3-phosphate/3-phosphoglycerate redox couple. Ethanol administration slightly increased the liver ATP level, but the simultaneous administration of pyrazole eliminated this effect. Other adenine nucleotides and HPO4 2- were not changed. The changes in the rate of ethanol oxidation had no effect on the phosphorylation state in the fed liver. It is assumed that in the fed liver the phosphorylation state is so well stabilized that the redox level has no influence.", "contents": "Influence of ethanol oxidation rate on the lactate/pyruvate ratio and phosphorylation state of the liver in fed rats. The effect of the ethanol oxidation rate on the interaction between the phosphorylation state (the [ATP]/[ADP] X [HPO4]2- ratio) and the redox state (the free [NAD+]/[NADH] ratio) of the liver cytosol was studied in intact fed rats. The rate of ethanol oxidation was inhibited to different degrees with pyrazole. The ethanol oxidation rate had no influence on the liver lactate level but correlated significantly with the pyruvate level. Accordingly, a significant correlation was also found between the ethanol oxidation rate and the lactate/pyruvate ratio. The rate of ethanol oxidation correlated significantly with the liver 3-phosphoglycerate level. No change in the glyceraldehyde-3-phosphate level was found. No correlation was found between the ethanol oxidation rate and the glyceraldehyde-3-phosphate/3-phosphoglycerate redox couple. Ethanol administration slightly increased the liver ATP level, but the simultaneous administration of pyrazole eliminated this effect. Other adenine nucleotides and HPO4 2- were not changed. The changes in the rate of ethanol oxidation had no effect on the phosphorylation state in the fed liver. It is assumed that in the fed liver the phosphorylation state is so well stabilized that the redox level has no influence."}
{"id": "PMID:188282", "title": "Demonstration of corticotrophin-releasing activity in rat and human peripheral blood.", "content": "Corticotrophin-releasing activity of rat or human peripheral blood was examined with a sensitive in vitro CRF bioassay, using cultured rat adenohypophyseal cells and ACTH measurement by radioimmunoassay. A dose-related ACTH secretion into the medium occurred in response to plasma or serum obtained from unstressed rats or humans. The minimum effective dose was 2.5 mul (0.1% of the medium concentration). No concomitant release of TSH occurred, indicating that cellular destruction was not the source of ACTH in the medium. As previously found with hypothalamic extract, 50% of the maximum ACTH secretion produced by a given quantity of plasma occurred within 1-5 min. Fifty per cent of CRF activity was retained after plasma was boiled for 5 min. CRF activity of serum was not different in intact, 1-10 min ether-stressed, adrenalectomized, hypophysectomized or dexamethasone-treated rats. There was no significant difference in CRF activity between serum from intact rats and those with complete forebrain removal and hypophysectomy, indicating that serum CRF originates from a source outside the forebrain or pituitary. Because of the lack of correlation of blood CRF activity with conditions in which there are marked differences in in vivo ACTH concentration, it is possible that the blood CRF activity we measure is non-specific.", "contents": "Demonstration of corticotrophin-releasing activity in rat and human peripheral blood. Corticotrophin-releasing activity of rat or human peripheral blood was examined with a sensitive in vitro CRF bioassay, using cultured rat adenohypophyseal cells and ACTH measurement by radioimmunoassay. A dose-related ACTH secretion into the medium occurred in response to plasma or serum obtained from unstressed rats or humans. The minimum effective dose was 2.5 mul (0.1% of the medium concentration). No concomitant release of TSH occurred, indicating that cellular destruction was not the source of ACTH in the medium. As previously found with hypothalamic extract, 50% of the maximum ACTH secretion produced by a given quantity of plasma occurred within 1-5 min. Fifty per cent of CRF activity was retained after plasma was boiled for 5 min. CRF activity of serum was not different in intact, 1-10 min ether-stressed, adrenalectomized, hypophysectomized or dexamethasone-treated rats. There was no significant difference in CRF activity between serum from intact rats and those with complete forebrain removal and hypophysectomy, indicating that serum CRF originates from a source outside the forebrain or pituitary. Because of the lack of correlation of blood CRF activity with conditions in which there are marked differences in in vivo ACTH concentration, it is possible that the blood CRF activity we measure is non-specific."}
{"id": "PMID:188288", "title": "Histochemical manifestations of early and late changes induced by Aflatoxin in rats.", "content": "Wistar rats were intraperitoneally treated with different doses of Aflatoxin B1 (5 and 7 mg/kg body weight) and sacrificed after various periods (6, 24, 48, 72 h, 5, 6, 7, 8, 9, 10 days and 86, 96, 97 weeks) in an attempt to detect liver, lung, intestine, spleen, mesenteric lymph nodes alterations. There are histochemical indications to suggest early liver changes for both doses in carbohydrates metabolism (decreasing of: polysaccharides, acid and neutral mucopolysaccharides, LD activity diffusely distributed through the all lobule). After 86, 96, 97 weeks from Aflatoxin administration, hepatocytes alterations rendered evident by fat accumulations, depletion or loss of polysaccharides, acid and neutral mucopolysaccharides, loss of cytoplasmic enzymes activities, altered pattern of surface ATP-ase are associated with diffuse fibrosis. The findings are suggestive that liver alterations are depending on dose and duration of exposure and could be detected by histochemical methods before significant morphological changes appear.", "contents": "Histochemical manifestations of early and late changes induced by Aflatoxin in rats. Wistar rats were intraperitoneally treated with different doses of Aflatoxin B1 (5 and 7 mg/kg body weight) and sacrificed after various periods (6, 24, 48, 72 h, 5, 6, 7, 8, 9, 10 days and 86, 96, 97 weeks) in an attempt to detect liver, lung, intestine, spleen, mesenteric lymph nodes alterations. There are histochemical indications to suggest early liver changes for both doses in carbohydrates metabolism (decreasing of: polysaccharides, acid and neutral mucopolysaccharides, LD activity diffusely distributed through the all lobule). After 86, 96, 97 weeks from Aflatoxin administration, hepatocytes alterations rendered evident by fat accumulations, depletion or loss of polysaccharides, acid and neutral mucopolysaccharides, loss of cytoplasmic enzymes activities, altered pattern of surface ATP-ase are associated with diffuse fibrosis. The findings are suggestive that liver alterations are depending on dose and duration of exposure and could be detected by histochemical methods before significant morphological changes appear."}
{"id": "PMID:188289", "title": "Time course of proteolytic enzyme alterations in the motor end-plates after stimulation.", "content": "Authors studied the proteolytic enzyme activity of motor end plates in the diaphragms and M. flexor digitorum brevis of rats after administration of cholinesterase inhibitors and after supramaximal electric stimulation, using the colour film digestion technique. Enhanced enzyme activity characterizing stimulated motor end plates persisted up to 12 h after stimulation. No proteolytic activity could be shown any more 24 h after stimulation, indicating restoration of the resting state. The role of metabolites (oligopeptides and amino-acids) released by the function-dependent axoterminal proteolysis is discussed in relation to neurochemical transmission processes.", "contents": "Time course of proteolytic enzyme alterations in the motor end-plates after stimulation. Authors studied the proteolytic enzyme activity of motor end plates in the diaphragms and M. flexor digitorum brevis of rats after administration of cholinesterase inhibitors and after supramaximal electric stimulation, using the colour film digestion technique. Enhanced enzyme activity characterizing stimulated motor end plates persisted up to 12 h after stimulation. No proteolytic activity could be shown any more 24 h after stimulation, indicating restoration of the resting state. The role of metabolites (oligopeptides and amino-acids) released by the function-dependent axoterminal proteolysis is discussed in relation to neurochemical transmission processes."}
{"id": "PMID:188286", "title": "Diagnostic significance of fasting serum bile acid in liver disease.", "content": "Serum bile acid was extracted with Amberlite XAD-2 followed by determination with an enzymatic and fluorimetric technique. Normal value for fasting serum bile acid was found to be 3 +/- 2 muM. Serum bile acid level was raised markedly early in the course of acute viral hepatitis, subsequently fell rapidly before resolution of biochemical tests, and was elevated again in relapse. In chronic liver disease serum bile acid was elevated moderately and correlated roughly with disease severity. In comparison with routine biochemical tests, serum bile acid correlated significantly with serum bilirubin, BSP retention and other hepatic tests, except serum cholesterol. Thus fasting serum bile acid level is a reliable screening test for a variety of liver disease to assess functional and morphological impairment of the liver.", "contents": "Diagnostic significance of fasting serum bile acid in liver disease. Serum bile acid was extracted with Amberlite XAD-2 followed by determination with an enzymatic and fluorimetric technique. Normal value for fasting serum bile acid was found to be 3 +/- 2 muM. Serum bile acid level was raised markedly early in the course of acute viral hepatitis, subsequently fell rapidly before resolution of biochemical tests, and was elevated again in relapse. In chronic liver disease serum bile acid was elevated moderately and correlated roughly with disease severity. In comparison with routine biochemical tests, serum bile acid correlated significantly with serum bilirubin, BSP retention and other hepatic tests, except serum cholesterol. Thus fasting serum bile acid level is a reliable screening test for a variety of liver disease to assess functional and morphological impairment of the liver."}
{"id": "PMID:188292", "title": "Conformational motility in D-glyceraldehyde-3-phosphate dehydrogenase influenced by subunit interactions.", "content": "Binding of four molecules of NAD to pig muscle glyceraldehyde-3-phosphate dehydrogenase decreases the apparent reactivity of Cys-153 -- a residue exposed only temporarily -- towards PMB in all four subunits of the enzyme. However, the change of reactivity is not a linear function of the degree of saturation with coenzyme, inasmuch as the first two, tightly bound NAD's exert a much larger effect than do the other two. The apparent reactivity of Cys-153 was investigated in GAPD's produced by hybridization of enzymes modified on residue Cys-149 with different reagents. The homotetramer-NAD complexes of these modified species were shown to exhibit different dissociation constants: native GAPD less than (alkylated--Cys-149)-GAPD less than (mercaptidated--Cys-149)-GAPD. The tight binding of 2 NAD's on the hybrid tetramers decreases the reactivity to the same extent in liganded and non-liganded subunits. The decrease in the apparent reactivity of Cys-153 is due to the restriction of local conformational motility around thes residue. Binding of NAD shifts the equilibrium towards a more closed form of the protein, whereas the rate constant of mercaptide formation itself remains unaltered. These findings suggest that the NAD-induced conformational changes are also reflected in the local fluctuation of the protein around Cys-153. The subunit interactions still operate in the hybrids and mediate the NAD-induced conformational changes.", "contents": "Conformational motility in D-glyceraldehyde-3-phosphate dehydrogenase influenced by subunit interactions. Binding of four molecules of NAD to pig muscle glyceraldehyde-3-phosphate dehydrogenase decreases the apparent reactivity of Cys-153 -- a residue exposed only temporarily -- towards PMB in all four subunits of the enzyme. However, the change of reactivity is not a linear function of the degree of saturation with coenzyme, inasmuch as the first two, tightly bound NAD's exert a much larger effect than do the other two. The apparent reactivity of Cys-153 was investigated in GAPD's produced by hybridization of enzymes modified on residue Cys-149 with different reagents. The homotetramer-NAD complexes of these modified species were shown to exhibit different dissociation constants: native GAPD less than (alkylated--Cys-149)-GAPD less than (mercaptidated--Cys-149)-GAPD. The tight binding of 2 NAD's on the hybrid tetramers decreases the reactivity to the same extent in liganded and non-liganded subunits. The decrease in the apparent reactivity of Cys-153 is due to the restriction of local conformational motility around thes residue. Binding of NAD shifts the equilibrium towards a more closed form of the protein, whereas the rate constant of mercaptide formation itself remains unaltered. These findings suggest that the NAD-induced conformational changes are also reflected in the local fluctuation of the protein around Cys-153. The subunit interactions still operate in the hybrids and mediate the NAD-induced conformational changes."}
{"id": "PMID:188287", "title": "The modulation of the prostaglandin-induced (E1, E2, F2alpha) motility of the large intestine by the adrenergic system.", "content": "The effect of adrenergic stimulating and inhibiting drugson the prostaglandin-dependent colonmotility in man was examined. By stimulating the adrenergic beta-receptors the prostaglandin-induced contractions were reduced and finally eliminated...", "contents": "The modulation of the prostaglandin-induced (E1, E2, F2alpha) motility of the large intestine by the adrenergic system. The effect of adrenergic stimulating and inhibiting drugson the prostaglandin-dependent colonmotility in man was examined. By stimulating the adrenergic beta-receptors the prostaglandin-induced contractions were reduced and finally eliminated..."}
{"id": "PMID:188293", "title": "Some characteristics of phosphorylation and dephosphorylation of proteins of isolated rat liver nuclei.", "content": "The phosphorylation and dephosphorylation reactions of the proteins of isolated rat liver nuclei were examined in the presence of ATP. It was shown that the plateau value of the phosphorus incorporation at high concentrations of ATP is the result of an equilibrium of phosphorylation and dephosphorylation. The data of 32P-labelling experiments and those of chemical determination of net change of phosphorus content were compared. The activity of an efficient protein phosphatase in rat liver nuclei is demonstrated. It was shown that the pool of protein-phosphorus in the nuclei is heterogeneous as regards its turnover rate. A protein-phosphorus fraction of high turnover dominates the picture of phosphorylation and dephosphorylation reactions when studied with [gamma-32P] ATP in vitro.", "contents": "Some characteristics of phosphorylation and dephosphorylation of proteins of isolated rat liver nuclei. The phosphorylation and dephosphorylation reactions of the proteins of isolated rat liver nuclei were examined in the presence of ATP. It was shown that the plateau value of the phosphorus incorporation at high concentrations of ATP is the result of an equilibrium of phosphorylation and dephosphorylation. The data of 32P-labelling experiments and those of chemical determination of net change of phosphorus content were compared. The activity of an efficient protein phosphatase in rat liver nuclei is demonstrated. It was shown that the pool of protein-phosphorus in the nuclei is heterogeneous as regards its turnover rate. A protein-phosphorus fraction of high turnover dominates the picture of phosphorylation and dephosphorylation reactions when studied with [gamma-32P] ATP in vitro."}
{"id": "PMID:188295", "title": "Effect of modification of SH-groups in D-glyceraldehyde-3-phosphate dehydrogenase on the properties of enzyme--coenzyme complex.", "content": "The NAD-binding of pig muscle glyceraldehyde-3-phosphate dehydrogenase after modifying certain SH-groups of the enzyme was studied by spectrophotometric titration and gel-chromatography. The enzyme modified on residue Cys-149 with N-ethylmaleimide, iodoacetate or p-mercuribenzoate binds NAD less tightly than does the unmodified enzyme. However, the differences between the NAD-binding sites characteristic of the native tetrameric enzyme are largely retained in the modified enzyme. Residue Cys-153 is near to the surface of the enzyme and is temporarily exposed due to the fluctuation of the protein. It can be modified only after blocking Cys-149. Modification of residue Cys-153 with N-ethylmaleimide does not further influence NAD-binding. Reaction of Cys-153 with p-mercuribenzoate does not directly cause the release of NAD. In this case the enzyme-coenzyme complex decomposes due to secondary conformational changes. This followed from the finding that the disappearance of the absorption band characteristic of the enzyme-coenzyme charge transfer complex is a first order process is equal to that of the structural changes following mercaptide formation of Cys-153.", "contents": "Effect of modification of SH-groups in D-glyceraldehyde-3-phosphate dehydrogenase on the properties of enzyme--coenzyme complex. The NAD-binding of pig muscle glyceraldehyde-3-phosphate dehydrogenase after modifying certain SH-groups of the enzyme was studied by spectrophotometric titration and gel-chromatography. The enzyme modified on residue Cys-149 with N-ethylmaleimide, iodoacetate or p-mercuribenzoate binds NAD less tightly than does the unmodified enzyme. However, the differences between the NAD-binding sites characteristic of the native tetrameric enzyme are largely retained in the modified enzyme. Residue Cys-153 is near to the surface of the enzyme and is temporarily exposed due to the fluctuation of the protein. It can be modified only after blocking Cys-149. Modification of residue Cys-153 with N-ethylmaleimide does not further influence NAD-binding. Reaction of Cys-153 with p-mercuribenzoate does not directly cause the release of NAD. In this case the enzyme-coenzyme complex decomposes due to secondary conformational changes. This followed from the finding that the disappearance of the absorption band characteristic of the enzyme-coenzyme charge transfer complex is a first order process is equal to that of the structural changes following mercaptide formation of Cys-153."}
{"id": "PMID:188296", "title": "Improvement in peripheral nerve function immediately after haemodialysis.", "content": "During haemodialysis there is a growth in the amplitude of muscle and nerve action potentials evoked by median nerve stimulation. It is therefore suggested that even a single period of haemodialysis causes some temporary improvement in the defective peripheral nerve function that accompanies uraemia.", "contents": "Improvement in peripheral nerve function immediately after haemodialysis. During haemodialysis there is a growth in the amplitude of muscle and nerve action potentials evoked by median nerve stimulation. It is therefore suggested that even a single period of haemodialysis causes some temporary improvement in the defective peripheral nerve function that accompanies uraemia."}
{"id": "PMID:188297", "title": "Krabbe's disease. A light and electron microscopic study.", "content": "Ultrastructural studies of brain and sural nerve biopsy specimens from a patient with Krabbe's disease disclosed periodically constricted or twisted tubules in addition to the more abundant and characteristic crystalloid and prismatic structures within macrophages. It is suggested that the twisted tubules may result from the intracellular accumulation of lactosyl ceramide. Familiarity with these unusual tubular structures is of practical as well as theoretical importance since they may be encountered in brain and peripheral nerve biopsy specimens obtained for the morphological diagnosis of Krabbe's disease.", "contents": "Krabbe's disease. A light and electron microscopic study. Ultrastructural studies of brain and sural nerve biopsy specimens from a patient with Krabbe's disease disclosed periodically constricted or twisted tubules in addition to the more abundant and characteristic crystalloid and prismatic structures within macrophages. It is suggested that the twisted tubules may result from the intracellular accumulation of lactosyl ceramide. Familiarity with these unusual tubular structures is of practical as well as theoretical importance since they may be encountered in brain and peripheral nerve biopsy specimens obtained for the morphological diagnosis of Krabbe's disease."}
{"id": "PMID:188298", "title": "Calcification of the perineurium. A case report.", "content": "Necropsy of a patient who died of uremia complicating juvenile diabetes revealed selective calcification of the perineurial sheaths in the sciatic nerves. The calcium phosphate deposits were limited to the outer layers of the perineurium while the innermost lamellae were free. Structural analysis, including electron diffraction and X-ray microanalysis, showed electron-dense, spicular deposits, which were composed mainly of finely crystallized hydroxyapatite. The end-stage diabetic nephropathy of the patient was associated with an extremely high calcium phosphorus ion product known to favour metastatic calcification. The mechanism of the selective localization of the calcium phosphate deposits to the outer layers of the perineurial sheaths is discussed with reference to the structure and suggested barrier function of the perineurium in regard to phosphate ions.", "contents": "Calcification of the perineurium. A case report. Necropsy of a patient who died of uremia complicating juvenile diabetes revealed selective calcification of the perineurial sheaths in the sciatic nerves. The calcium phosphate deposits were limited to the outer layers of the perineurium while the innermost lamellae were free. Structural analysis, including electron diffraction and X-ray microanalysis, showed electron-dense, spicular deposits, which were composed mainly of finely crystallized hydroxyapatite. The end-stage diabetic nephropathy of the patient was associated with an extremely high calcium phosphorus ion product known to favour metastatic calcification. The mechanism of the selective localization of the calcium phosphate deposits to the outer layers of the perineurial sheaths is discussed with reference to the structure and suggested barrier function of the perineurium in regard to phosphate ions."}
{"id": "PMID:188299", "title": "Intramembrane particle distribution and lectin binding of glioblastoma cells after long term subculture.", "content": "Human glioblastoma cells in long-term monolayer culture showed an even distribution of intramembrane particles (IMP) on all surfaces of the plasma membrane; junctional complexes were rarely observed and rectilinear arrays were not seen. Cells treated with Con A-ferritin and Ricin II-ferritin showed an even distribution of lectin receptors and under conditions used no capping occurred. Lectin-ferritin complexes were taken up into pinocytotic vesicles. Cleaved preparations of Ricin II-ferritin treated cells showed no change in the distribution of IMP.", "contents": "Intramembrane particle distribution and lectin binding of glioblastoma cells after long term subculture. Human glioblastoma cells in long-term monolayer culture showed an even distribution of intramembrane particles (IMP) on all surfaces of the plasma membrane; junctional complexes were rarely observed and rectilinear arrays were not seen. Cells treated with Con A-ferritin and Ricin II-ferritin showed an even distribution of lectin receptors and under conditions used no capping occurred. Lectin-ferritin complexes were taken up into pinocytotic vesicles. Cleaved preparations of Ricin II-ferritin treated cells showed no change in the distribution of IMP."}
{"id": "PMID:188300", "title": "Presenile dementia with Alzheimer-, Pick- and Lewy-body changes.", "content": "An autopsy case of unclassifiable presenil dementia is reported. The outstanding pathological findings were as follows; 1. presence of senile plaques, neurofibrillary changes, Pick bodies, Hirano bodies, granulovacuolar degeneration of neurons, etc. 2. numerous Lewy bodies in the brain stem and diencephalon, 3. peculiar swollen neurons with intracytoplasmic, eosinophilic and argentophilic inclusions (\"Lewy-like-bodies\") in the cerebral cortices. Detailed study of the last mentioned inclusions indicates that they are almost identical to Lewy bodies, though there are some minor differences, in histochemical and electronmicroscopic findings. Nosologically, this case may represent either a combination of Alzheimer's disease, Pick's disease and idiopathic Parkinsonism with \"Lewy-like-bodies\" in the cerebral cortices, or a single disease. As far as we know, no similar case been reported.", "contents": "Presenile dementia with Alzheimer-, Pick- and Lewy-body changes. An autopsy case of unclassifiable presenil dementia is reported. The outstanding pathological findings were as follows; 1. presence of senile plaques, neurofibrillary changes, Pick bodies, Hirano bodies, granulovacuolar degeneration of neurons, etc. 2. numerous Lewy bodies in the brain stem and diencephalon, 3. peculiar swollen neurons with intracytoplasmic, eosinophilic and argentophilic inclusions (\"Lewy-like-bodies\") in the cerebral cortices. Detailed study of the last mentioned inclusions indicates that they are almost identical to Lewy bodies, though there are some minor differences, in histochemical and electronmicroscopic findings. Nosologically, this case may represent either a combination of Alzheimer's disease, Pick's disease and idiopathic Parkinsonism with \"Lewy-like-bodies\" in the cerebral cortices, or a single disease. As far as we know, no similar case been reported."}
{"id": "PMID:188304", "title": "High density lipoprotein concentrations in newborn infants.", "content": "The lipoprotein pattern was analyzed by agarose gel electrophoresis in 19 new born infants of varying gestational age. The HDL concentration was determined by rocket immunoelectrophoresis in another 41 newborn infants. Infants with a gestational age of less than 33 weeks had very low HDL concentrations compared to preterm infants with a gestational age of less than or equal to 33 weeks and term ihfants. In the first 5-10 days after birth the HDL concentration increased markedly in preterm infants (gestational age less than 37 weeks) whereas it remained unchanged in term infants.", "contents": "High density lipoprotein concentrations in newborn infants. The lipoprotein pattern was analyzed by agarose gel electrophoresis in 19 new born infants of varying gestational age. The HDL concentration was determined by rocket immunoelectrophoresis in another 41 newborn infants. Infants with a gestational age of less than 33 weeks had very low HDL concentrations compared to preterm infants with a gestational age of less than or equal to 33 weeks and term ihfants. In the first 5-10 days after birth the HDL concentration increased markedly in preterm infants (gestational age less than 37 weeks) whereas it remained unchanged in term infants."}
{"id": "PMID:188306", "title": "Telecobalt therapy for malignant lung tumours.", "content": "The authors present the results of telecobalt therapy in 194 patients with malignant lung tumours treated between 1967 and 1971. The 3- and 5-year survivals were 9.7 and 5.4% respectively, with an average survival of 15 months. The results obtained depend on the microscopy, the clinical staging and on the irradiation techniques possible; several prognostic groups may be distinguished.", "contents": "Telecobalt therapy for malignant lung tumours. The authors present the results of telecobalt therapy in 194 patients with malignant lung tumours treated between 1967 and 1971. The 3- and 5-year survivals were 9.7 and 5.4% respectively, with an average survival of 15 months. The results obtained depend on the microscopy, the clinical staging and on the irradiation techniques possible; several prognostic groups may be distinguished."}
{"id": "PMID:188307", "title": "Changes in the activities of nucleoside triphosphatases and nucleoside kinases in Vero cells infected with Simian virus 40.", "content": "Changes in the activities of three enzymes involved in nucleotide metabolism were studied following infection of Vero cells with SV40. The results showed that SV40 infection enhanced the activities of uridine phosphokinase and UMP phosphokinase involved in nucleotide synthesis and suppressed the activity of nucleoside triphosphatases involved in nulceotide degradation. These SV40-induced enzyme activity changes probably served to somehow increase the quantity of nucleotides for virus proliferation.", "contents": "Changes in the activities of nucleoside triphosphatases and nucleoside kinases in Vero cells infected with Simian virus 40. Changes in the activities of three enzymes involved in nucleotide metabolism were studied following infection of Vero cells with SV40. The results showed that SV40 infection enhanced the activities of uridine phosphokinase and UMP phosphokinase involved in nucleotide synthesis and suppressed the activity of nucleoside triphosphatases involved in nulceotide degradation. These SV40-induced enzyme activity changes probably served to somehow increase the quantity of nucleotides for virus proliferation."}
{"id": "PMID:188308", "title": "Spontaneous malignant transformation in two epithelial cell lines of rat liver cells.", "content": "The cellular morphology, chromosomal structure, and tumorigenicity of two lines (B and J-13) of rat epithelial cells were examined serially during in vitro cultivation. The cells for such cultures were derived from the hepatic tissues of two 7-day-old male rats of the Donryu strain. The cultured cells were first inoculated into newborn syngenetic rats on the 641st day in vitro (80th subcultures) for line B, and on the 446th day (58 subcultures) for line J-13. The inoculated cells produced tumors with hemorrhagic ascites in rats after long latent periods, viz, 215-599 days in line B and 170-369 days in line J-13. All the tumors were undifferentiated hepatocarcinomas. The pleomorphism in shape and size of the cultured cells gradually became obvious with time of cultivation and was more pronounced in recultured tumor cells. Chromosomes of the culured cells were a normal diploid pattern until about the 200th day in vitro, but thereafter the modal chromsome number shifted to hypodiploid or hypotriploid via hypodiploid stages. The chromosome constitution of recultured tumor cells resembled that of inoculated cells in number distribution, but had changed to a more complicated karyotype. In experiments with line B, the same marker chromosome was detected in all tumor cells analyzed as had been present in inoculated cells.", "contents": "Spontaneous malignant transformation in two epithelial cell lines of rat liver cells. The cellular morphology, chromosomal structure, and tumorigenicity of two lines (B and J-13) of rat epithelial cells were examined serially during in vitro cultivation. The cells for such cultures were derived from the hepatic tissues of two 7-day-old male rats of the Donryu strain. The cultured cells were first inoculated into newborn syngenetic rats on the 641st day in vitro (80th subcultures) for line B, and on the 446th day (58 subcultures) for line J-13. The inoculated cells produced tumors with hemorrhagic ascites in rats after long latent periods, viz, 215-599 days in line B and 170-369 days in line J-13. All the tumors were undifferentiated hepatocarcinomas. The pleomorphism in shape and size of the cultured cells gradually became obvious with time of cultivation and was more pronounced in recultured tumor cells. Chromosomes of the culured cells were a normal diploid pattern until about the 200th day in vitro, but thereafter the modal chromsome number shifted to hypodiploid or hypotriploid via hypodiploid stages. The chromosome constitution of recultured tumor cells resembled that of inoculated cells in number distribution, but had changed to a more complicated karyotype. In experiments with line B, the same marker chromosome was detected in all tumor cells analyzed as had been present in inoculated cells."}
{"id": "PMID:188305", "title": "The effect of ACTH on oxygen uptake by skeletal muscle, brain, liver, kidney and myocardium slices of the rat.", "content": "Using Wartburg's method the effect of ACTH on oxygen uptake by slices of various tissues of the rat was investigated in relation to the duration of ACTH action in the organism. A reduction in oxygen uptake by tissue slices was found 1 hour after ACTH injection with a rise after 16 hours. It seems that in the first phase ACTH exerts an inhibitory effect on tissue respiration indirectly through the adrenal cortex, while in the second phase it may exert a stimulatory influence either directly or by some other mechanisms.", "contents": "The effect of ACTH on oxygen uptake by skeletal muscle, brain, liver, kidney and myocardium slices of the rat. Using Wartburg's method the effect of ACTH on oxygen uptake by slices of various tissues of the rat was investigated in relation to the duration of ACTH action in the organism. A reduction in oxygen uptake by tissue slices was found 1 hour after ACTH injection with a rise after 16 hours. It seems that in the first phase ACTH exerts an inhibitory effect on tissue respiration indirectly through the adrenal cortex, while in the second phase it may exert a stimulatory influence either directly or by some other mechanisms."}
{"id": "PMID:188310", "title": "Studies on cartilage formation. XX. Histochemical investigation of some enzymes of glycogen metabolsim in regenerative articular surfaces.", "content": "In 28 dogs the distal articular cartilage of the femur was removed and the regenerating articular surface on the 70th postoperative day was studied histochemically for hexokinase, glucose-6-phosphatase, phosphohexose-isomerase, fructose-1, 6-diphosphatase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, lactate dehydrogenase isoenzymes, phosphoglucomutase, phosphorylase, glycogen synthetase, UDP--glucose dehydrogenase, and UDP-glucuronic acid-4-epimerase. The articular surface consisted of fibrous tissue and of cartilage islets. The latter contained cells differentiating into cartilage and young chondrocytes. The glycolytic enzymes reacted positively in the regenerative articular surface. Enzyme activities were higher in the cells (particularly the chondroblasts and young chondrocytes) of the cartilage islets than in the connective tissue. In the cells differentiations into cartilage, beside the LDH isoenzymes characteristic of glycolysis, a significant LDH1 and LDH2 activity was observed. At the same site the presence of fructose-1, 6-diphosphatase-activity could be assumed, but there was no glucose-6-phosphatase activity. Glycogen synthesis proceeded in the cells of the cartilage islets and UDP-glucuronic acid-4-epimerase activity was observed in the differentiated cells. UDP-glucose dehydrogenase activity was positive in every section of the articular surface.", "contents": "Studies on cartilage formation. XX. Histochemical investigation of some enzymes of glycogen metabolsim in regenerative articular surfaces. In 28 dogs the distal articular cartilage of the femur was removed and the regenerating articular surface on the 70th postoperative day was studied histochemically for hexokinase, glucose-6-phosphatase, phosphohexose-isomerase, fructose-1, 6-diphosphatase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, lactate dehydrogenase isoenzymes, phosphoglucomutase, phosphorylase, glycogen synthetase, UDP--glucose dehydrogenase, and UDP-glucuronic acid-4-epimerase. The articular surface consisted of fibrous tissue and of cartilage islets. The latter contained cells differentiating into cartilage and young chondrocytes. The glycolytic enzymes reacted positively in the regenerative articular surface. Enzyme activities were higher in the cells (particularly the chondroblasts and young chondrocytes) of the cartilage islets than in the connective tissue. In the cells differentiations into cartilage, beside the LDH isoenzymes characteristic of glycolysis, a significant LDH1 and LDH2 activity was observed. At the same site the presence of fructose-1, 6-diphosphatase-activity could be assumed, but there was no glucose-6-phosphatase activity. Glycogen synthesis proceeded in the cells of the cartilage islets and UDP-glucuronic acid-4-epimerase activity was observed in the differentiated cells. UDP-glucose dehydrogenase activity was positive in every section of the articular surface."}
{"id": "PMID:188312", "title": "Cyclic nucleotides in bacteria.", "content": "The question of the ubiquity of cyclic AMP in bacteria is not yet closed. The recent introduction of more sensitive and reliable assays for cyclic AMP should settle the problem. My prediction is that although there may be some organisms that do not contain cyclic AMP, they probably have some yet undiscovered regulatory nucleotides that play similar roles. Although cyclic AMP has been shown to be unessential for growth of E. coli under optimal laboratory conditions in glucose-containing medium, it undoubtedly can play a role in survival. Cyclic AMP allows bacteria to adapt to a variety of new nutritional conditions. The significance of the observations that cyclic AMP shows a concentration-dependent stimulation or inhibition of growth rate in E. coli is not yet clear. The pathways regulated by cyclic AMP are, for the most part, those which involve carbon metabolism. On the other hand, pathways of nitrogen metabolism are not uniformly regulated by cyclic AMP. In several organisms, some nitrogen pathways are regulated by glutamine synthetase. Specialized processes such as the formation of flagella, fruiting bodies, and buds often appear to be controlled by cyclic AMP. This is similar to the situation in mammalian cells wherein many differentiated functions are regulated by cyclic AMP. Catabolite repression can be explained by an inhibition of the synthesis of cyclic AMP, which does not require an invocation of a primary effect of catabolite action on cyclic AMP phosphodiesterase or on a secretory process, although these two processes are probably of secondary importance. There are some fundamental similarities between the effects of catabolites in inhibiting E. coli adenylyl cyclase and the effects of hormones on mammalian adenylyl cyclase. Both processes require the interaction of the effector with a membrane-bound receptor and may transmit the inhibitory or stimulatory signal to adenylyl cyclase via some coupling factor. Cyclic GMP is clearly present in bacteria, although the features of its molecular biology are just beginning to be laid out. How many other regulatory nucleotides, whether cyclic or linear, remain to be found in bacteria is a problem for the future.", "contents": "Cyclic nucleotides in bacteria. The question of the ubiquity of cyclic AMP in bacteria is not yet closed. The recent introduction of more sensitive and reliable assays for cyclic AMP should settle the problem. My prediction is that although there may be some organisms that do not contain cyclic AMP, they probably have some yet undiscovered regulatory nucleotides that play similar roles. Although cyclic AMP has been shown to be unessential for growth of E. coli under optimal laboratory conditions in glucose-containing medium, it undoubtedly can play a role in survival. Cyclic AMP allows bacteria to adapt to a variety of new nutritional conditions. The significance of the observations that cyclic AMP shows a concentration-dependent stimulation or inhibition of growth rate in E. coli is not yet clear. The pathways regulated by cyclic AMP are, for the most part, those which involve carbon metabolism. On the other hand, pathways of nitrogen metabolism are not uniformly regulated by cyclic AMP. In several organisms, some nitrogen pathways are regulated by glutamine synthetase. Specialized processes such as the formation of flagella, fruiting bodies, and buds often appear to be controlled by cyclic AMP. This is similar to the situation in mammalian cells wherein many differentiated functions are regulated by cyclic AMP. Catabolite repression can be explained by an inhibition of the synthesis of cyclic AMP, which does not require an invocation of a primary effect of catabolite action on cyclic AMP phosphodiesterase or on a secretory process, although these two processes are probably of secondary importance. There are some fundamental similarities between the effects of catabolites in inhibiting E. coli adenylyl cyclase and the effects of hormones on mammalian adenylyl cyclase. Both processes require the interaction of the effector with a membrane-bound receptor and may transmit the inhibitory or stimulatory signal to adenylyl cyclase via some coupling factor. Cyclic GMP is clearly present in bacteria, although the features of its molecular biology are just beginning to be laid out. How many other regulatory nucleotides, whether cyclic or linear, remain to be found in bacteria is a problem for the future."}
{"id": "PMID:188315", "title": "Cyclic AMP and gastric secretion: the illusive second messenger.", "content": "We have surveyed the literature which bears upon the contention that accumulation of intracellular cyclic AMP is a necessary intermediate event between secretagogue and secretion of acid by the stomach. In our view, the evidence in favor of this hypothesis is wanting for these three reasons: (i) the evidence does not fit with better established information about regulation of gastric secretion and about hormonal actions on the cyclic AMP system; (ii) technological problems involved in the biological preparations employed and in the assay procedures used make the evidence nearly uninterpretable; and (iii) there exists a body of contradictory evidence at least as convincing as that which favors the thesis. These three arguments against acceptance of the theory are not definitive and are not intended to dissuade investigators interested in gastric mucosal metabolism from their quest. And, although we are not at this time adherents of the preceding hypothesis, we are also not unmindful of its basic appeal, which has attracted numerous scientists into a study of the metabolic correlates of gastric acid secretion. Unfortunately the general appeal of the second messenger hypothesis is such as to make it almost a paradigm of gastric secretory physiology in the seventies, in Kuhn's sense of that word (118). The disadvantages of paradigms are that they tend to obscure negative evidence among their adherents, and they arouse controversies more marked by heat than by light.", "contents": "Cyclic AMP and gastric secretion: the illusive second messenger. We have surveyed the literature which bears upon the contention that accumulation of intracellular cyclic AMP is a necessary intermediate event between secretagogue and secretion of acid by the stomach. In our view, the evidence in favor of this hypothesis is wanting for these three reasons: (i) the evidence does not fit with better established information about regulation of gastric secretion and about hormonal actions on the cyclic AMP system; (ii) technological problems involved in the biological preparations employed and in the assay procedures used make the evidence nearly uninterpretable; and (iii) there exists a body of contradictory evidence at least as convincing as that which favors the thesis. These three arguments against acceptance of the theory are not definitive and are not intended to dissuade investigators interested in gastric mucosal metabolism from their quest. And, although we are not at this time adherents of the preceding hypothesis, we are also not unmindful of its basic appeal, which has attracted numerous scientists into a study of the metabolic correlates of gastric acid secretion. Unfortunately the general appeal of the second messenger hypothesis is such as to make it almost a paradigm of gastric secretory physiology in the seventies, in Kuhn's sense of that word (118). The disadvantages of paradigms are that they tend to obscure negative evidence among their adherents, and they arouse controversies more marked by heat than by light."}
{"id": "PMID:188323", "title": "Estrogen biosynthesis in the ovaries and testes.", "content": "This review has presented some of our recent data on estrogen biosynthesis and has drawn upon these, as well as numerous observations, to design the two-cell type, two-gonadotropin model, applicable to both sexes, for the biosynthesis of gonadal estrogens and its regulation. Some of the data upon which this model, depicted in Figure 15, are based are quite preliminary and in many cases have been derived from experiments with tissues from animals over a rather narrow age span. Consequently, in future years this model may appear too simplistic to explain gonadal estrogen synthesis at all stages of development. However, whatever the fate of the model, whether it be broken and rebuilt on firmer foundations or furnished more lavishly, it is hoped that it will result in some of the corners being \"rounded.\" There has been an emphasis on some of the similarities between the two sexes with respect to enzyme capacities, hormone receptors, and control mechanisms for the various cell types in the ovaries as compared to the testes. In particular, the striking similarities both structurally and functionally between Sertoli cells and granulosa cells are now recognized. Vive la difference.", "contents": "Estrogen biosynthesis in the ovaries and testes. This review has presented some of our recent data on estrogen biosynthesis and has drawn upon these, as well as numerous observations, to design the two-cell type, two-gonadotropin model, applicable to both sexes, for the biosynthesis of gonadal estrogens and its regulation. Some of the data upon which this model, depicted in Figure 15, are based are quite preliminary and in many cases have been derived from experiments with tissues from animals over a rather narrow age span. Consequently, in future years this model may appear too simplistic to explain gonadal estrogen synthesis at all stages of development. However, whatever the fate of the model, whether it be broken and rebuilt on firmer foundations or furnished more lavishly, it is hoped that it will result in some of the corners being \"rounded.\" There has been an emphasis on some of the similarities between the two sexes with respect to enzyme capacities, hormone receptors, and control mechanisms for the various cell types in the ovaries as compared to the testes. In particular, the striking similarities both structurally and functionally between Sertoli cells and granulosa cells are now recognized. Vive la difference."}
{"id": "PMID:188329", "title": "Characterization of an adenylate cyclase system sensitive to histamine H2-receptor excitation in cells from dog gastric mucosa.", "content": "A method of preparing viable cells from dog gastric mucosa is described. Cyclic AMP in these cells is elevated by histamine and 4-methyl histamine but 2-methyl histamine is only a weak agonist. The effects on cyclic AMP levels are inhibited competitively by metiamide and burimamide which give apparent KBvalues of 3.5x10-7 M and 2.3x10-6 M, respectively. These values are similar to those reported for other histamine H2-receptor systems. The H1-receptor antagonists, mepyramine and chlorpheniramine, have no inhibitory effect on the histamine induced elevation of cyclic AMP: promethazine inhibits the system but not by a competitive mechanism. It is concluded that the histamine stimulated adenylate cyclase system is probably located in the parietal cell component.", "contents": "Characterization of an adenylate cyclase system sensitive to histamine H2-receptor excitation in cells from dog gastric mucosa. A method of preparing viable cells from dog gastric mucosa is described. Cyclic AMP in these cells is elevated by histamine and 4-methyl histamine but 2-methyl histamine is only a weak agonist. The effects on cyclic AMP levels are inhibited competitively by metiamide and burimamide which give apparent KBvalues of 3.5x10-7 M and 2.3x10-6 M, respectively. These values are similar to those reported for other histamine H2-receptor systems. The H1-receptor antagonists, mepyramine and chlorpheniramine, have no inhibitory effect on the histamine induced elevation of cyclic AMP: promethazine inhibits the system but not by a competitive mechanism. It is concluded that the histamine stimulated adenylate cyclase system is probably located in the parietal cell component."}
{"id": "PMID:188330", "title": "The swollen leg.", "content": "Systemic causes of leg edema include idiopathic cyclic edema, heart failure, cirrhosis, nephrosis and other hypoproteinemic states. Lymphedema may be primary, or secondary to neoplasm, lymphangitis, retroperitoneal fibrosis and, rarely (in the U.S.), filariasis. Thrombophlebitis and chronic venous insufficiency are not uncommon causes. Finally, infection, ischemia, lipedema, vascular anomalies, tumors and trauma can be responsible for the swollen leg.", "contents": "The swollen leg. Systemic causes of leg edema include idiopathic cyclic edema, heart failure, cirrhosis, nephrosis and other hypoproteinemic states. Lymphedema may be primary, or secondary to neoplasm, lymphangitis, retroperitoneal fibrosis and, rarely (in the U.S.), filariasis. Thrombophlebitis and chronic venous insufficiency are not uncommon causes. Finally, infection, ischemia, lipedema, vascular anomalies, tumors and trauma can be responsible for the swollen leg."}
{"id": "PMID:188331", "title": "Comparison of foundry dust evaluation by various methods.", "content": "Matched sets of dust samples were collected in gray iron foundries for the purpose of comparing results obtained by four sampling techniques. Both respirable and total dust samples were collected. The results are compared on the basis of total concentration and on the basis of silica content. The problems in obtaining an adequate sample for silica analysis are considered. A proposal is made for using total respirable dust as an index of permissible dustiness in foundries.", "contents": "Comparison of foundry dust evaluation by various methods. Matched sets of dust samples were collected in gray iron foundries for the purpose of comparing results obtained by four sampling techniques. Both respirable and total dust samples were collected. The results are compared on the basis of total concentration and on the basis of silica content. The problems in obtaining an adequate sample for silica analysis are considered. A proposal is made for using total respirable dust as an index of permissible dustiness in foundries."}
{"id": "PMID:188332", "title": "Mechanisms contributing to myocardial accumulation of technetium-99m stannous pyrophosphate after coronary arterial occlusion.", "content": "The relation between the accumulation of pyrophosphate and technetium-99m in myocardium with reversible and irreversible ischmic injury was studied in dogs subjected to transitory or persistent coronary arterial occlusion. Among four dogs with coronary occlusion maintained for less than 20 minutes, none had either increased MB creatine kinase (CK) (the \"myocardial\" CK isoenzyme) activity serum or a positive 99mTc stannous pyrophosphate image. Seven dogs with coronary occlusion maintained for 30 or more minutes had elevated serum MB CK activity, and five of the seven had positive (abnormal) images. Thus, although false negative images may occur occasionally despite myocardial damage, both increased serum MB CK and abnormal images generally accompanied prolonged coronary occlusion. In contrast, ischemia without infarction was not associated with abnormal images. Both 99mTc and 32P labeled pyrophosphate were accumulated extensively and proportionally in myocardium from zones of infarction, and uptake of both tracers was comparable although modest in isolated mitochondria. Similar results were obtained after myocardial infarction in animals with induced profound leukopenia. Thus, phagocytosis of the radiopharmaceutical agent by leukocytes migrating into the infarct is not an essential mechanism accounting for uptake. These results indicate that abnormal images reflect uptake of pyrophosphate, associated with 99mTc, by irreversibly injured myocardium rather than leukocytic infiltration involved in the inflammatory response in the heart.", "contents": "Mechanisms contributing to myocardial accumulation of technetium-99m stannous pyrophosphate after coronary arterial occlusion. The relation between the accumulation of pyrophosphate and technetium-99m in myocardium with reversible and irreversible ischmic injury was studied in dogs subjected to transitory or persistent coronary arterial occlusion. Among four dogs with coronary occlusion maintained for less than 20 minutes, none had either increased MB creatine kinase (CK) (the \"myocardial\" CK isoenzyme) activity serum or a positive 99mTc stannous pyrophosphate image. Seven dogs with coronary occlusion maintained for 30 or more minutes had elevated serum MB CK activity, and five of the seven had positive (abnormal) images. Thus, although false negative images may occur occasionally despite myocardial damage, both increased serum MB CK and abnormal images generally accompanied prolonged coronary occlusion. In contrast, ischemia without infarction was not associated with abnormal images. Both 99mTc and 32P labeled pyrophosphate were accumulated extensively and proportionally in myocardium from zones of infarction, and uptake of both tracers was comparable although modest in isolated mitochondria. Similar results were obtained after myocardial infarction in animals with induced profound leukopenia. Thus, phagocytosis of the radiopharmaceutical agent by leukocytes migrating into the infarct is not an essential mechanism accounting for uptake. These results indicate that abnormal images reflect uptake of pyrophosphate, associated with 99mTc, by irreversibly injured myocardium rather than leukocytic infiltration involved in the inflammatory response in the heart."}
{"id": "PMID:188333", "title": "Estrogen use in postmenopausal women.", "content": "Fifteen per cent of postmenopausal women living in a retirement community used oral estrogens. Both use and new-use continued in the seventh, eighth and ninth decades of life, although use and age-specific use-prevalence declined after age 70. Mean duration of most recent continuous use was 105 months. Vaginal estrogenic preparations were used infrequently, briefly, and usually by women who also used oral estrogens in the same year. The most commonly used oral estrogenic preparation was conjugated equine estrogens (Premarin).", "contents": "Estrogen use in postmenopausal women. Fifteen per cent of postmenopausal women living in a retirement community used oral estrogens. Both use and new-use continued in the seventh, eighth and ninth decades of life, although use and age-specific use-prevalence declined after age 70. Mean duration of most recent continuous use was 105 months. Vaginal estrogenic preparations were used infrequently, briefly, and usually by women who also used oral estrogens in the same year. The most commonly used oral estrogenic preparation was conjugated equine estrogens (Premarin)."}
{"id": "PMID:188334", "title": "Acute hemorrhagic conjunctivitis: a mixed virus outbreak among Vietnamese refugees on Guam.", "content": "In May 1975 the authors investigated an outbreak of acute hemorrhagic conjunctivitis that affected an estimated 29,000 refugees from South Vietnam who stayed on Guam while en route to the United States. Illness usually lasted6-10 days and was characterized by conjunctival injection (100%), lid edema (84%), eye irritation (81%) and subconjunctival  hemorrhages (45%). Conjunctival swabs and paired serum specimens on a limited number of patients implicated enterovirus 70 as a major etiologic agent and adenovirus 11 as a less frequent agent. Adenovirus 8 and herpes simplex virus caused concurrent, sporadic cases of keratoconjunctivitis. Forty-three per cent of the refugees in a sample of 604 refugees were affected, and the attack rate was highest on evacuation vessels where crowding and poor sanitation facilitated person-to-person spread of infection. Because the outbreak subsided on Guam, and because infection was transmitted there to only 13 of about 1300 Americans in frequent contact with affected refugees, the risk of secondary outbreaks inthe United States appeared small.", "contents": "Acute hemorrhagic conjunctivitis: a mixed virus outbreak among Vietnamese refugees on Guam. In May 1975 the authors investigated an outbreak of acute hemorrhagic conjunctivitis that affected an estimated 29,000 refugees from South Vietnam who stayed on Guam while en route to the United States. Illness usually lasted6-10 days and was characterized by conjunctival injection (100%), lid edema (84%), eye irritation (81%) and subconjunctival  hemorrhages (45%). Conjunctival swabs and paired serum specimens on a limited number of patients implicated enterovirus 70 as a major etiologic agent and adenovirus 11 as a less frequent agent. Adenovirus 8 and herpes simplex virus caused concurrent, sporadic cases of keratoconjunctivitis. Forty-three per cent of the refugees in a sample of 604 refugees were affected, and the attack rate was highest on evacuation vessels where crowding and poor sanitation facilitated person-to-person spread of infection. Because the outbreak subsided on Guam, and because infection was transmitted there to only 13 of about 1300 Americans in frequent contact with affected refugees, the risk of secondary outbreaks inthe United States appeared small."}
{"id": "PMID:188335", "title": "Stability of aqueous perchlorate formulations.", "content": "The stability of three aqueous perchlorate formulations used in nuclear medicine was studied as a function of the formulation and storage temperature. The formulations were intravenous potassium perchlorate solution, oral sodium perchlorate-sorbitol solution and oral potassium perchlorate in cherry syrup solution. The assays were conducted gravimetrically by precipitation with tetra-n-pentylammonium bromide. All formulations were found to be stable at least nine months. It is recommended that any formulation containing potassium perchlorate be kept at room temperature since precipitation of the active ingredient may occur if refrigerated. Sodium perchlorate formulations, however, may be refrigerated if desired because of their greater solubility.", "contents": "Stability of aqueous perchlorate formulations. The stability of three aqueous perchlorate formulations used in nuclear medicine was studied as a function of the formulation and storage temperature. The formulations were intravenous potassium perchlorate solution, oral sodium perchlorate-sorbitol solution and oral potassium perchlorate in cherry syrup solution. The assays were conducted gravimetrically by precipitation with tetra-n-pentylammonium bromide. All formulations were found to be stable at least nine months. It is recommended that any formulation containing potassium perchlorate be kept at room temperature since precipitation of the active ingredient may occur if refrigerated. Sodium perchlorate formulations, however, may be refrigerated if desired because of their greater solubility."}
{"id": "PMID:188336", "title": "Benign hepatic tumors and oral contraceptive pills.", "content": "In order to consider possible environmental factors related to the development of benign hepatic tumors, all reports of this disorder in the case records of five different hospitals in Rochester, New York, during the past 10 years were reviewed. Seven patients with benign hepatic tumors of the liver and two with peliosis hepatis were identified. Among the seven with a benign hepatic tumor, four were women currently receiving oral contraceptives; one had been receiving this medication in the past, and two had no history of exposure to any steroid whatsoever. The two patients with peliosis hepatis were receiving long-term androgenic anabolic steroids. Dilated, thin-walled vessels and vascular spaces were a more prominent feature of the tumor seen in four patients receiving oral contraceptive pills. It is emphasized in this report that benign hepatic tumors do occur in men and in patients with cirrhotic liver without the use of any kind of steroids.", "contents": "Benign hepatic tumors and oral contraceptive pills. In order to consider possible environmental factors related to the development of benign hepatic tumors, all reports of this disorder in the case records of five different hospitals in Rochester, New York, during the past 10 years were reviewed. Seven patients with benign hepatic tumors of the liver and two with peliosis hepatis were identified. Among the seven with a benign hepatic tumor, four were women currently receiving oral contraceptives; one had been receiving this medication in the past, and two had no history of exposure to any steroid whatsoever. The two patients with peliosis hepatis were receiving long-term androgenic anabolic steroids. Dilated, thin-walled vessels and vascular spaces were a more prominent feature of the tumor seen in four patients receiving oral contraceptive pills. It is emphasized in this report that benign hepatic tumors do occur in men and in patients with cirrhotic liver without the use of any kind of steroids."}
{"id": "PMID:188338", "title": "Plasma human placental lactogen, oxytocinase, and placental phosphatase in normal and toxemic pregnancies.", "content": "A total of 625 serum samples were drawn from 400 normal and 225 hypertensive toxemic pregnant women. Each sample was simultaneously assayed for its human placental lactogen (HPL), oxytocinase (O), and placental phosphatase (PP) concentration. In addition, accurate placental and infant birth weights were determined in those cases where the serum sample was obtained within 14 days of delivery. The results showed a significant rise and correlation of each of the three proteins with increasing weeks of gestation. Although the infant birth weight was unrelated to the serum level of the three proteins, both the HPL and O concentrations were significantly correlated with the placental weight in the normal pregnancies. In both types of pregnancies, the concentration of O was significantly related to that of PP and this was also true for HPL and O and HPL and PP. In all instances O was more strongly related than PP. In the toxemic pregnancies there was a higher O and lower PP level than in normal gestations. These data suggest that placental enzyme measurements, especially O, could be clinically helpful in monitoring high-risk pregnancies.", "contents": "Plasma human placental lactogen, oxytocinase, and placental phosphatase in normal and toxemic pregnancies. A total of 625 serum samples were drawn from 400 normal and 225 hypertensive toxemic pregnant women. Each sample was simultaneously assayed for its human placental lactogen (HPL), oxytocinase (O), and placental phosphatase (PP) concentration. In addition, accurate placental and infant birth weights were determined in those cases where the serum sample was obtained within 14 days of delivery. The results showed a significant rise and correlation of each of the three proteins with increasing weeks of gestation. Although the infant birth weight was unrelated to the serum level of the three proteins, both the HPL and O concentrations were significantly correlated with the placental weight in the normal pregnancies. In both types of pregnancies, the concentration of O was significantly related to that of PP and this was also true for HPL and O and HPL and PP. In all instances O was more strongly related than PP. In the toxemic pregnancies there was a higher O and lower PP level than in normal gestations. These data suggest that placental enzyme measurements, especially O, could be clinically helpful in monitoring high-risk pregnancies."}
{"id": "PMID:188339", "title": "Etiologic factors in the pathogenesis of liver tumors associated with oral contraceptives.", "content": "Within the last several years, previously rare liver tumors have been seen in young women using oral contraceptive steroids. The Registry for Liver Tumors Associated with Oral Contraceptives at the University of California, Irvine, has clearly identified 27 cases. The recent literature contains 44 case reports. Common to these 71 cases has been a histopathologic diagnosis of focal nodular hyperplasia, adenoma, hamartoma, and hepatoma. Significant statistical etiologic factors include prolonged uninterrupted usage of oral contraceptive steroids. Eight deaths and liver rupture in 18 patients attest to the seriousness of this new potentially lethal adverse phenomenon.", "contents": "Etiologic factors in the pathogenesis of liver tumors associated with oral contraceptives. Within the last several years, previously rare liver tumors have been seen in young women using oral contraceptive steroids. The Registry for Liver Tumors Associated with Oral Contraceptives at the University of California, Irvine, has clearly identified 27 cases. The recent literature contains 44 case reports. Common to these 71 cases has been a histopathologic diagnosis of focal nodular hyperplasia, adenoma, hamartoma, and hepatoma. Significant statistical etiologic factors include prolonged uninterrupted usage of oral contraceptive steroids. Eight deaths and liver rupture in 18 patients attest to the seriousness of this new potentially lethal adverse phenomenon."}
{"id": "PMID:188337", "title": "An insulinoma without fasting hypoglycemia.", "content": "A patient with a 25-year history of episodic irritability, confusion, and unconsciousness was suspected of having organic hypoglycemia. He was fasted for a 72-hour period without developing symptoms. At the end of the fast his blood sugar was 85 mg/100 ml and the immunoreactive insulin (IRI) concentraion was elevated to 350 microunits/ml. Surgical exploration demonstrated a 4 x 3 centimeter insulinoma in the tail of the pancreas. Since proinsulin-like components (PLC) are known to be elevated in patients with islet cell tumors and have only 5 to 10 per cent of the biologic activity of insulin, it is suggested that a major portion of the IRI was PLC. This case demonstrates that the inability to withstand prolonged fasting does not exclude the diagnosis of an insulinoma and suggests a mechanism whereby such patients can tolerate fasting.", "contents": "An insulinoma without fasting hypoglycemia. A patient with a 25-year history of episodic irritability, confusion, and unconsciousness was suspected of having organic hypoglycemia. He was fasted for a 72-hour period without developing symptoms. At the end of the fast his blood sugar was 85 mg/100 ml and the immunoreactive insulin (IRI) concentraion was elevated to 350 microunits/ml. Surgical exploration demonstrated a 4 x 3 centimeter insulinoma in the tail of the pancreas. Since proinsulin-like components (PLC) are known to be elevated in patients with islet cell tumors and have only 5 to 10 per cent of the biologic activity of insulin, it is suggested that a major portion of the IRI was PLC. This case demonstrates that the inability to withstand prolonged fasting does not exclude the diagnosis of an insulinoma and suggests a mechanism whereby such patients can tolerate fasting."}
{"id": "PMID:188341", "title": "The influence of prostaglandin G2 on platelet ultrastructure and platelet secretion.", "content": "Prostaglandin G2 (PGG2) is a labile endoperoxide produced physiologically following exposure of platelets to aggregating agents. We report here studies using isolated PGG2. This agent stimulates a concentration-dependent internal platelet contraction very similar to that produced by the calcium ionophore A23187. EDTA prevented platelet aggregation but did not prevent PGG2-stimulated internal contraction or secretion. In contrast, prostaglandin E1 and dibutyryl cyclic AMP inhich selectively labilizes platelet granules, was added to platelets together with PGG2 there was a superadditive effect on platelet secretion. Thus, granule labilization induced by PMA is a separable phenomenon and complementary to the effect of PGG2 on contraction. The ultimate degree of secretion is dependent on both processes. Studies using additional inhibitors supported the hypothesis that PGG2 activates platelets (either directly or following conversion to thromboxane A2) by transporting calcium from an intracellular store to the cytoplasmic site of the platelet contractile proteins.", "contents": "The influence of prostaglandin G2 on platelet ultrastructure and platelet secretion. Prostaglandin G2 (PGG2) is a labile endoperoxide produced physiologically following exposure of platelets to aggregating agents. We report here studies using isolated PGG2. This agent stimulates a concentration-dependent internal platelet contraction very similar to that produced by the calcium ionophore A23187. EDTA prevented platelet aggregation but did not prevent PGG2-stimulated internal contraction or secretion. In contrast, prostaglandin E1 and dibutyryl cyclic AMP inhich selectively labilizes platelet granules, was added to platelets together with PGG2 there was a superadditive effect on platelet secretion. Thus, granule labilization induced by PMA is a separable phenomenon and complementary to the effect of PGG2 on contraction. The ultimate degree of secretion is dependent on both processes. Studies using additional inhibitors supported the hypothesis that PGG2 activates platelets (either directly or following conversion to thromboxane A2) by transporting calcium from an intracellular store to the cytoplasmic site of the platelet contractile proteins."}
{"id": "PMID:188342", "title": "Lithium-induced diuretic effect of antidiuretic hormone in rats.", "content": "The effect of a low dose of lithium (1 meq/kg per day) on renal function and its response to antidiuretic hormone (ADH) was studied in unanesthetized rats. This dose of lithium itself had no influence on renal water and electrolyte excretion, but lithium-treated rats responded paradoxically to exogenous ADH by increases in urinary volume, excretion of total solutes, sodium, potassium, and phosphate. Administration of ADH in the presence of lithium led to a lowering of urine osmolality, but free water clearance was not significantly reduced. Adenylate cyclase from the renal medulla of animals treated with ADH and lithium had a lower response to synthetic vasopressin in vitro than in animals treated with lithium alone. The results suggest that exogenous ADHis diuretic in the presence of a low concentration of lithilm. The predominant mechanism for this diuresis is probably inhibition of electrolyte and isomotic water reabbsorption in various nephron segments, including those proximal to the collecting ducts. ADH also markedly increased urinary excretion of lithium and appears to promote accumulation of lithium in the renal medulla.", "contents": "Lithium-induced diuretic effect of antidiuretic hormone in rats. The effect of a low dose of lithium (1 meq/kg per day) on renal function and its response to antidiuretic hormone (ADH) was studied in unanesthetized rats. This dose of lithium itself had no influence on renal water and electrolyte excretion, but lithium-treated rats responded paradoxically to exogenous ADH by increases in urinary volume, excretion of total solutes, sodium, potassium, and phosphate. Administration of ADH in the presence of lithium led to a lowering of urine osmolality, but free water clearance was not significantly reduced. Adenylate cyclase from the renal medulla of animals treated with ADH and lithium had a lower response to synthetic vasopressin in vitro than in animals treated with lithium alone. The results suggest that exogenous ADHis diuretic in the presence of a low concentration of lithilm. The predominant mechanism for this diuresis is probably inhibition of electrolyte and isomotic water reabbsorption in various nephron segments, including those proximal to the collecting ducts. ADH also markedly increased urinary excretion of lithium and appears to promote accumulation of lithium in the renal medulla."}
{"id": "PMID:188343", "title": "Central antihypertensive effects of inhibitors of the renin-angiotensin system in rats.", "content": "The possibility that mean arterial pressure (MA) might be maintained by an effect of angiotensin II or its precursors on the central nervous system in rats made hypertensive by occluding the aorta between the renal arteries was investigated. Aortic coarctation produced severe hypertension (MAP greater than 150 mmHg) and plasma renin activity values (radioimmunoassay) at least 10 times normal within 2-6 days after surgery. [Sar1, IIe8]angiotensin II, an angiotensin II antagonist administered centrally via an intracerebroventricular (icv) injection (10-100 mug), lowered the MAP in a dose-dependent manner. Peripheral administration of [Sar1, IIe8]angiotensin II (bolus injection) at 100 mug intra-arterially was ineffective, but the antagonist did lower arterial pressure when infused intravenously for 1 h at 4 times this dose. Less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, a converting enzyme inhibitor, and pepstatin, a renin inhibitor, were ineffective via an icv injection. These results suggest that angiotensin II is in part responsible for the elevation in blood pressure following aortic coarctation in rats. Both central and peripheral administration of [Sar1, Ile8]-angiotensin II lowered mean arterial pressure but the antagonist lowered arterial pressure at lower doses and produced a more rapid decline in arterial pressure when administered into the central nervous system then when administered intra-arterially or intravenously.", "contents": "Central antihypertensive effects of inhibitors of the renin-angiotensin system in rats. The possibility that mean arterial pressure (MA) might be maintained by an effect of angiotensin II or its precursors on the central nervous system in rats made hypertensive by occluding the aorta between the renal arteries was investigated. Aortic coarctation produced severe hypertension (MAP greater than 150 mmHg) and plasma renin activity values (radioimmunoassay) at least 10 times normal within 2-6 days after surgery. [Sar1, IIe8]angiotensin II, an angiotensin II antagonist administered centrally via an intracerebroventricular (icv) injection (10-100 mug), lowered the MAP in a dose-dependent manner. Peripheral administration of [Sar1, IIe8]angiotensin II (bolus injection) at 100 mug intra-arterially was ineffective, but the antagonist did lower arterial pressure when infused intravenously for 1 h at 4 times this dose. Less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, a converting enzyme inhibitor, and pepstatin, a renin inhibitor, were ineffective via an icv injection. These results suggest that angiotensin II is in part responsible for the elevation in blood pressure following aortic coarctation in rats. Both central and peripheral administration of [Sar1, Ile8]-angiotensin II lowered mean arterial pressure but the antagonist lowered arterial pressure at lower doses and produced a more rapid decline in arterial pressure when administered into the central nervous system then when administered intra-arterially or intravenously."}
{"id": "PMID:188344", "title": "In vivo control of mitochondrial enzyme concentrations and activity by oxygen.", "content": "Newborn and adult dog heart mitochondria were prepared from animals chronically adjusted to varying arterial oxygen tensions. Similarly, rat liver and heart mitochondria were isolated from animals acutely exposed to lowered inspired oxygen. After isolation, all mitochondrial samples were assayed under normoxic conditions. These experiments illustrated the following effects of oxygen on mitochondrial function: 1) respiratory activity in State 3 or in the uncoupled state increased after hypoxia and decreased after increased in vivo oxygenation; 2) similarly, the turnover of cytochrome oxidase increased in hypoxia and decreased after increased oxygenation; 3) after chronic hypoxia cytochrome oxidase, cytochrome c and b concentrations decreased per miligram of mitochondrial protein; 4) all mitochondrial preparations were well coupled and exhibited normal capabilities to perform oxidative phosphorylation. The data are interpreted to indicate sensitive control of mitochondrial respiratory capacities by oxygen in vivo.", "contents": "In vivo control of mitochondrial enzyme concentrations and activity by oxygen. Newborn and adult dog heart mitochondria were prepared from animals chronically adjusted to varying arterial oxygen tensions. Similarly, rat liver and heart mitochondria were isolated from animals acutely exposed to lowered inspired oxygen. After isolation, all mitochondrial samples were assayed under normoxic conditions. These experiments illustrated the following effects of oxygen on mitochondrial function: 1) respiratory activity in State 3 or in the uncoupled state increased after hypoxia and decreased after increased in vivo oxygenation; 2) similarly, the turnover of cytochrome oxidase increased in hypoxia and decreased after increased oxygenation; 3) after chronic hypoxia cytochrome oxidase, cytochrome c and b concentrations decreased per miligram of mitochondrial protein; 4) all mitochondrial preparations were well coupled and exhibited normal capabilities to perform oxidative phosphorylation. The data are interpreted to indicate sensitive control of mitochondrial respiratory capacities by oxygen in vivo."}
{"id": "PMID:188345", "title": "A halfway house for mentally ill offenders.", "content": "The authors describe the resocialization of recovering mentally ill male offenders through the halfway house program to which they were released. A number of guiding principles are discussed in connection with the care of this high-risk population. Partial residence for those about tp be discharged from the hospital was one feature of the program. Evaluation of the program after three years showed a lower than average rate of recidivism and relatively low operating costs; in addition, it appeared that predictions regarding possible dangerousness can be made with greater confidence when halfway house residence is part of the treatment plan for this type of population.", "contents": "A halfway house for mentally ill offenders. The authors describe the resocialization of recovering mentally ill male offenders through the halfway house program to which they were released. A number of guiding principles are discussed in connection with the care of this high-risk population. Partial residence for those about tp be discharged from the hospital was one feature of the program. Evaluation of the program after three years showed a lower than average rate of recidivism and relatively low operating costs; in addition, it appeared that predictions regarding possible dangerousness can be made with greater confidence when halfway house residence is part of the treatment plan for this type of population."}
{"id": "PMID:188346", "title": "A progressive approach to the problem of foodborne infections.", "content": "Qualitative and quantitative bacteriological examinations of 100 samples of perishable foods from 39 retail stores were performed to determine the presence of bacterial contaminants and to explore the feasibility of establishing and utilizing microbiological standards in enforcement. Forty-six per cent of the samples had standard plate counts in excess of 100,000 per gram, 17 per cent showed coliform organisms in excess of 100 per gram, 20 per cent revealed the presence of Staphylococcus aureus and 2 per cent Clostridium perfringens. None of the shell fish samples grew Vibrio parahaemolyticus. The bacteriological findings are discussed in relation to pertinent variables and the use of microbiological standards for potentially hazardous foods is explored. All 450 retail food establishments in a selected area of Western Suffolk County (New York) were subjected to comprehensive study, using a scoring system developed by the Food and Drug Administration. Initial inspections revealed 32 per cent as having one or more major violations. Follow-up inspections were performed to insure compliance and most violations were corrected within four weeks. Six months later all establishments were reinspected. The scoring system was found to have limited value. Half the establishments with major violations on initial inspection had major violations six months later as compared to less than a quarter of those with no initial major violation.", "contents": "A progressive approach to the problem of foodborne infections. Qualitative and quantitative bacteriological examinations of 100 samples of perishable foods from 39 retail stores were performed to determine the presence of bacterial contaminants and to explore the feasibility of establishing and utilizing microbiological standards in enforcement. Forty-six per cent of the samples had standard plate counts in excess of 100,000 per gram, 17 per cent showed coliform organisms in excess of 100 per gram, 20 per cent revealed the presence of Staphylococcus aureus and 2 per cent Clostridium perfringens. None of the shell fish samples grew Vibrio parahaemolyticus. The bacteriological findings are discussed in relation to pertinent variables and the use of microbiological standards for potentially hazardous foods is explored. All 450 retail food establishments in a selected area of Western Suffolk County (New York) were subjected to comprehensive study, using a scoring system developed by the Food and Drug Administration. Initial inspections revealed 32 per cent as having one or more major violations. Follow-up inspections were performed to insure compliance and most violations were corrected within four weeks. Six months later all establishments were reinspected. The scoring system was found to have limited value. Half the establishments with major violations on initial inspection had major violations six months later as compared to less than a quarter of those with no initial major violation."}
{"id": "PMID:188347", "title": "Renal cell carcinoma in a patient successfully treated for Wilms's tumor.", "content": "A woman who had received successful therapy for Wilm's tumor of one kidney in childhood developed renal cell carcinoma in the opposite kidney 21 years later. Such an occurrence has not been reported previously. A discussion of the differential diagnosis of calcified renal mass lesions and the angiographic differentiation between Wilms's tumor and renal cell carcinoma is presented. The possible relationship between these two primary renal tumors is considered.", "contents": "Renal cell carcinoma in a patient successfully treated for Wilms's tumor. A woman who had received successful therapy for Wilm's tumor of one kidney in childhood developed renal cell carcinoma in the opposite kidney 21 years later. Such an occurrence has not been reported previously. A discussion of the differential diagnosis of calcified renal mass lesions and the angiographic differentiation between Wilms's tumor and renal cell carcinoma is presented. The possible relationship between these two primary renal tumors is considered."}
{"id": "PMID:188348", "title": "Acrodysostosis coinciding with pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism.", "content": "The diagnosis of acrodysostosis has been differentiated from that of pseudohypoparathyroidism or pseudo-pseudohypoparathyroidism by the absence of endocrine abnormalities, more generalized osseous abnormalities, and a characteristic facial appearance. Two cases are presented which fulfill all of the major features of acrodysostosis: peripheral dysostosis, nasal hypoplasia (pug nose), and mental retardation. The first case had all the metabolic abnormalities of pseudohypoparathyroidism; the second case had urinary cyclic adenosine-3',5'-monophosphate findings suggestive of pseudo-pseudohypoparathyroidism. Therefore acrodysostosis cannot be differentiated from pseudohypoparathyroidism or pseudopseudohypoparathyroidism on clinical and radiologic features only.", "contents": "Acrodysostosis coinciding with pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism. The diagnosis of acrodysostosis has been differentiated from that of pseudohypoparathyroidism or pseudo-pseudohypoparathyroidism by the absence of endocrine abnormalities, more generalized osseous abnormalities, and a characteristic facial appearance. Two cases are presented which fulfill all of the major features of acrodysostosis: peripheral dysostosis, nasal hypoplasia (pug nose), and mental retardation. The first case had all the metabolic abnormalities of pseudohypoparathyroidism; the second case had urinary cyclic adenosine-3',5'-monophosphate findings suggestive of pseudo-pseudohypoparathyroidism. Therefore acrodysostosis cannot be differentiated from pseudohypoparathyroidism or pseudopseudohypoparathyroidism on clinical and radiologic features only."}
{"id": "PMID:188349", "title": "Detection of pulmonary nodules by computed tomography.", "content": "In 11 of 23 patients, computed tomography of the chest detected pulmonary nodules that were not detected by conventional chest radiography or whole lung tomography. CT is recommended for patients suspected of having pulmonary metastasis and those with a solitary pulmonary nodule.", "contents": "Detection of pulmonary nodules by computed tomography. In 11 of 23 patients, computed tomography of the chest detected pulmonary nodules that were not detected by conventional chest radiography or whole lung tomography. CT is recommended for patients suspected of having pulmonary metastasis and those with a solitary pulmonary nodule."}
{"id": "PMID:188350", "title": "Ecological associations of vesicular stomatitis virus in rural Central America and Panama.", "content": "The principal objective of this study was to determine ecological associations of vesicular stomatitis virus (VSV)- New Jersey and VSV-Indiana in rural Central America and Panama. Two types of information were linked: the results of neutralizing antibody tests performed on sera from 3,232 lifetime residents of 189 rural study communitities of Central America and Panama, and ecological characteristics of the study communities as determined from natural resource atlases. The major finding was that neutralizing antibody acquistion to VSV-New Jersey was greatest for persons living at elevations between 350 and 649 meters, with relatively open, dry vegetation and distinct seasonal alternation of dry and moist (not wet) ground conditions. Similar ecological associations were found for VSV-Indiana, except that the risk of infection was also high in moist environments with dense tree cover. The results suggest that VSV-New Jersey and VSV-Indiana have similar but not identical maintenance and transmission cycles and that basic maintenance cycles for both viruses may exist in dry, open habitats rather than in tropicla rain forest habitats as was previously assumed for VSV-Indiana.", "contents": "Ecological associations of vesicular stomatitis virus in rural Central America and Panama. The principal objective of this study was to determine ecological associations of vesicular stomatitis virus (VSV)- New Jersey and VSV-Indiana in rural Central America and Panama. Two types of information were linked: the results of neutralizing antibody tests performed on sera from 3,232 lifetime residents of 189 rural study communitities of Central America and Panama, and ecological characteristics of the study communities as determined from natural resource atlases. The major finding was that neutralizing antibody acquistion to VSV-New Jersey was greatest for persons living at elevations between 350 and 649 meters, with relatively open, dry vegetation and distinct seasonal alternation of dry and moist (not wet) ground conditions. Similar ecological associations were found for VSV-Indiana, except that the risk of infection was also high in moist environments with dense tree cover. The results suggest that VSV-New Jersey and VSV-Indiana have similar but not identical maintenance and transmission cycles and that basic maintenance cycles for both viruses may exist in dry, open habitats rather than in tropicla rain forest habitats as was previously assumed for VSV-Indiana."}
{"id": "PMID:188356", "title": "Biophysical mechanisms of anesthetic action: historical perspective and review of current concepts.", "content": "The large number and diversity of anesthetic agents were evident to investigators 80 years ago, and suggested a physicochemical theory of anesthesia. Meyer and Overton were the first to offer a quantitative relationship between a physicochemical property and potency of anesthetic agents. They also focused attention on the lipid phase as the site of anesthetic action. Ferguson realized that the concentration of an agent at its site of action bears a generally unknown relation to the concentration in the external phase. However, at equilibrium the activity of an agent is the same in every phase, motivating Ferguson to suggest that activities rather than concentrations be used as indices of dosage. The critical-volume theory resulted from modification of the Meyer-Overton theory to include the molal volume of the anesthetic. The allowance for molal volume resulted initially from an attempt further to regularize the experimental data. The concept of a critical-volume fraction of anesthetic being necessary for narcosis was discussed in most detail by Mullins. Subsequently, the concept of the effect of the anesthetic has changed from filling of free space to expansion and fluidization of the membrane. The ability of pressure to cause excitant phenomena and antagonize anesthetics is predictable from the critical-volume theory and is therefore highly significant evidence. K. W. Miller and associates are perhaps most prominent in the recent quantification and formalization of the critical-volume theory and HPNS. The existence of a separate convulsant site(s) is suggested by the demonstration of significantly different compressibilities associated with anesthesia and convulsions. Work corroborating a separate convulsant site involved measurement of the partial molal volumes of a series of related convulsant and anesthetic ethers and calculation of each compound's solubility parameter. Multiple convulsant sites may exist, and these two methods may not have accessed the same site. Understanding the anesthetic-convulsant duality will have important practical application to deepwater diving, and may well offer important insight into the neurophysiologic and electrophysiologic effects of anesthetics. The application of ESR and NMR allows investigation at the molecular level of effects of anesthetics on biological and model membranes. Magnetic resonance techniques have generally supported the concept of membrane fluidization by anesthetics. Some investigators have recently attempted to displace the focus of attention from the lipid phase. However, the evidence is clearly against the aqueous-phase theory of Pauling and S.L. Miller. The microtubule theory of Allison and Nunn has not accumulated supporting evidence comparable to the lipid theories. Contradictory evidence makes any evaluation of this theory speculative. Additionally, the interspecies and intracellular variability of microtubules raises questions of the relevance of many studies...", "contents": "Biophysical mechanisms of anesthetic action: historical perspective and review of current concepts. The large number and diversity of anesthetic agents were evident to investigators 80 years ago, and suggested a physicochemical theory of anesthesia. Meyer and Overton were the first to offer a quantitative relationship between a physicochemical property and potency of anesthetic agents. They also focused attention on the lipid phase as the site of anesthetic action. Ferguson realized that the concentration of an agent at its site of action bears a generally unknown relation to the concentration in the external phase. However, at equilibrium the activity of an agent is the same in every phase, motivating Ferguson to suggest that activities rather than concentrations be used as indices of dosage. The critical-volume theory resulted from modification of the Meyer-Overton theory to include the molal volume of the anesthetic. The allowance for molal volume resulted initially from an attempt further to regularize the experimental data. The concept of a critical-volume fraction of anesthetic being necessary for narcosis was discussed in most detail by Mullins. Subsequently, the concept of the effect of the anesthetic has changed from filling of free space to expansion and fluidization of the membrane. The ability of pressure to cause excitant phenomena and antagonize anesthetics is predictable from the critical-volume theory and is therefore highly significant evidence. K. W. Miller and associates are perhaps most prominent in the recent quantification and formalization of the critical-volume theory and HPNS. The existence of a separate convulsant site(s) is suggested by the demonstration of significantly different compressibilities associated with anesthesia and convulsions. Work corroborating a separate convulsant site involved measurement of the partial molal volumes of a series of related convulsant and anesthetic ethers and calculation of each compound's solubility parameter. Multiple convulsant sites may exist, and these two methods may not have accessed the same site. Understanding the anesthetic-convulsant duality will have important practical application to deepwater diving, and may well offer important insight into the neurophysiologic and electrophysiologic effects of anesthetics. The application of ESR and NMR allows investigation at the molecular level of effects of anesthetics on biological and model membranes. Magnetic resonance techniques have generally supported the concept of membrane fluidization by anesthetics. Some investigators have recently attempted to displace the focus of attention from the lipid phase. However, the evidence is clearly against the aqueous-phase theory of Pauling and S.L. Miller. The microtubule theory of Allison and Nunn has not accumulated supporting evidence comparable to the lipid theories. Contradictory evidence makes any evaluation of this theory speculative. Additionally, the interspecies and intracellular variability of microtubules raises questions of the relevance of many studies..."}
{"id": "PMID:188357", "title": "Immunogenetic polymorphism of lipoproteins in swine. 1. Four additional serum beta-lipoprotein allotypes (Lpp2, Lpp4, Lpp5 and Lpp15) in the Lpp system.", "content": "Four additional swine serum lipoprotein allotypes are described. Specific anti-allotype reagents were obtained from alloimmune precipitating sera produced in lipoprotein-defined-type recipients immunized with normal sera and subsequently with lipoprotein fractions. Identification studies indicate that the four serologically defined low-density lipoprotein (LDL) variants, designated Lpp2, Lpp4, Lpp5 and Lpp15, are members of a previously described Lpp system. The individual specificities, Lpp2, Lpp4 and Lpp5, are determined by three co-dominant autosomal genes, Lpp2, Lpp4 and Lpp5, respectively, whereas the common specificity, Lpp15, is controlled by a complex of genetic information of the Lpp2 and Lpp4 genes, and by the two previously described alleles, Lpp1 and Lpp3; Lpp15 occurs on the same molecule with respective individual specificity. The Lpp5 and Lpp15 antigens behave as a pair of alternative allotypic specificities. The double immunodiffusion test in agar was employed to demonstrate independent phenotypic expression of each allelic gene in the Lpp heterozygous animals, for the analysis of the immune sera, and for lipoprotein testing of 3305 sera. Marked differences in gene frequencies were found between the swine breeds tested. As a result of characteristic frequencies, only nine of 15 possible Lpp genotypes were found in the breeding herds tested; the remaining six genotypes were obtained from testcross matings.", "contents": "Immunogenetic polymorphism of lipoproteins in swine. 1. Four additional serum beta-lipoprotein allotypes (Lpp2, Lpp4, Lpp5 and Lpp15) in the Lpp system. Four additional swine serum lipoprotein allotypes are described. Specific anti-allotype reagents were obtained from alloimmune precipitating sera produced in lipoprotein-defined-type recipients immunized with normal sera and subsequently with lipoprotein fractions. Identification studies indicate that the four serologically defined low-density lipoprotein (LDL) variants, designated Lpp2, Lpp4, Lpp5 and Lpp15, are members of a previously described Lpp system. The individual specificities, Lpp2, Lpp4 and Lpp5, are determined by three co-dominant autosomal genes, Lpp2, Lpp4 and Lpp5, respectively, whereas the common specificity, Lpp15, is controlled by a complex of genetic information of the Lpp2 and Lpp4 genes, and by the two previously described alleles, Lpp1 and Lpp3; Lpp15 occurs on the same molecule with respective individual specificity. The Lpp5 and Lpp15 antigens behave as a pair of alternative allotypic specificities. The double immunodiffusion test in agar was employed to demonstrate independent phenotypic expression of each allelic gene in the Lpp heterozygous animals, for the analysis of the immune sera, and for lipoprotein testing of 3305 sera. Marked differences in gene frequencies were found between the swine breeds tested. As a result of characteristic frequencies, only nine of 15 possible Lpp genotypes were found in the breeding herds tested; the remaining six genotypes were obtained from testcross matings."}
{"id": "PMID:188359", "title": "[Lymphadenopathy caused by hemophagocytic sinus histiocytosis (Destombes-Rosai-Dorfman syndrome). Immunologic and histopathologic study of a new case].", "content": "The case reported is one of lymphadenopathy due to haemophagocytic sinusal histiocytosis which had progressed for more than 10 years before resulting in death at the age of 58 years. In this advanced form, all superficial and deep nodes were involved. In addition to histiocytic hyperplasia, with haemophagocytosis and lipid overload, there was plasmocytic hyperplasia, i.e. B-lymphocytes, with polyclonal hypergamma-globulinaemia and an increase in the levels of many antibodies, in particular against rubella and the Epstein-Barr virus. The aetiopathological significance is discussed, in particular the role of an infection due to the EB virus.", "contents": "[Lymphadenopathy caused by hemophagocytic sinus histiocytosis (Destombes-Rosai-Dorfman syndrome). Immunologic and histopathologic study of a new case]. The case reported is one of lymphadenopathy due to haemophagocytic sinusal histiocytosis which had progressed for more than 10 years before resulting in death at the age of 58 years. In this advanced form, all superficial and deep nodes were involved. In addition to histiocytic hyperplasia, with haemophagocytosis and lipid overload, there was plasmocytic hyperplasia, i.e. B-lymphocytes, with polyclonal hypergamma-globulinaemia and an increase in the levels of many antibodies, in particular against rubella and the Epstein-Barr virus. The aetiopathological significance is discussed, in particular the role of an infection due to the EB virus."}
{"id": "PMID:188364", "title": "Role of triglyceride-rich lipoproteins in atherogenesis.", "content": "The hypothesis that chylomicron cholesterol is a causal factor in the accumulation of cholesterol in atheromatous lesions is compatible with the finding reported here that hypercholesterokmia in the cholesterol-fed rabbit is due, at least, in part, to the accumulation of chylomicron remnants. The presence of lipoprotein lipase in aorta suggests the possibility that chylomicron remnants are formed on the arterial surface and that they may be deposited in the deeper layers of the arterial wall without prior release into the bloodstream. Consequently, the cholesterol-rich lipo-proteins in the plasma may be the product rather than the precursor of the atherogenic process.", "contents": "Role of triglyceride-rich lipoproteins in atherogenesis. The hypothesis that chylomicron cholesterol is a causal factor in the accumulation of cholesterol in atheromatous lesions is compatible with the finding reported here that hypercholesterokmia in the cholesterol-fed rabbit is due, at least, in part, to the accumulation of chylomicron remnants. The presence of lipoprotein lipase in aorta suggests the possibility that chylomicron remnants are formed on the arterial surface and that they may be deposited in the deeper layers of the arterial wall without prior release into the bloodstream. Consequently, the cholesterol-rich lipo-proteins in the plasma may be the product rather than the precursor of the atherogenic process."}
{"id": "PMID:188367", "title": "The low-density lipoprotein pathway in human fibroblasts: relation between cell surface receptor binding and endocytosis of low-density lipoprotein.", "content": "The studies reported here, coupled with our previous studies, indicate that LDL is ingested by cultured human fibroblasts in a process that resembles adsorptive endocytosis. The critical step is the binding of the lipoprotein to a high-affinity cell surface receptor. Uptake of LDL by this receptor-mediated process permits the cell to aquire cholesterol from the lipoprotein, and this acquisition, in turn, suppresses the cell's own cholesterol synthesis and activates the cell's system for reesterification and storage of the incoming cholesterol. In cells from patients with the receptor-negative form of homozygous FH, the cell surface receptor is functionally absent. The absence of high-affinity binding to this receptor produces a defective uptake of LDL and prevents the normal process of feedback regulation of cholesterol synthesis by the lipoprotein. The physiologic importance of the LDL pathway is indicated by the fact that patients who lack the LDL receptor (FH homozygotes) develop both profound hyper-cholesterolemia and fulminant atherosclerosis. It is likely that other defects in the LDL pathway account for other forms of hypercholesterolemia and atherosclerosis in man.", "contents": "The low-density lipoprotein pathway in human fibroblasts: relation between cell surface receptor binding and endocytosis of low-density lipoprotein. The studies reported here, coupled with our previous studies, indicate that LDL is ingested by cultured human fibroblasts in a process that resembles adsorptive endocytosis. The critical step is the binding of the lipoprotein to a high-affinity cell surface receptor. Uptake of LDL by this receptor-mediated process permits the cell to aquire cholesterol from the lipoprotein, and this acquisition, in turn, suppresses the cell's own cholesterol synthesis and activates the cell's system for reesterification and storage of the incoming cholesterol. In cells from patients with the receptor-negative form of homozygous FH, the cell surface receptor is functionally absent. The absence of high-affinity binding to this receptor produces a defective uptake of LDL and prevents the normal process of feedback regulation of cholesterol synthesis by the lipoprotein. The physiologic importance of the LDL pathway is indicated by the fact that patients who lack the LDL receptor (FH homozygotes) develop both profound hyper-cholesterolemia and fulminant atherosclerosis. It is likely that other defects in the LDL pathway account for other forms of hypercholesterolemia and atherosclerosis in man."}
{"id": "PMID:188368", "title": "Hyperreactive arterial endothelial cells: a clue for the treatment of atherosclerosis.", "content": "Arterial endothelial cells, which are capable of phagocytizing carbon particles of the same size as beta- and pre-beta-lipoprotein, were found only in endothelial cells of arterial segments susceptible to atheromatous changes in susceptible animal species, and the distribution closely corresponded to the susceptibility. The distribution of such endothelial cells is dense in large arteries, in the openings to their branches, especially in downstream portions, of rabbits, hens, and cocks; however, the distribution is relatively scanty in arteries of rhesus monkeys and is very scanty in dogs. Carbon particles were also rare in the suckling rabbit and tended to increase with age. They were not found in Wistar rats but were found in spontaneously hypertensive rats, which showed a characteristically diffuse distribution, even in relatively small arteries. The carbon particles, phagocytized, were released to the subendothelial space but were difficult to pass through the internal elastic lamina and tended to stagnate there for more than one month. The authors therefore call these cells hyperreactive endothelial cells. Various vasoactive substances, such as angiotensin II, histamine, and serotonin, significantly enhanced the phagocytic activities of arotic endothelial cells in rabbits; epinephrine and norepinephrine also slightly enhanced these activities. Various smooth muscle relaxants, such as ATP, pyridinol carbamate (ATP synthesis-enhancing substance), cycli-AMP, dibutyryl cycli-AMP, phthalazinol (cyclic-AMP phosphodiesterase inhibitor), iproveratril (calcium entry-inhibiting substance), colchicine, and vinblastine, with their different modes of action, commonly inhibited phagocytic activities, a finding that suggests a significant role for contractile protein in the permeability problem of atherogenesis. The atheromatous lesions of cholesterol-fed rabbits exhibited a striking increase in hyperreactive endothelial cells, accompanied by a marked rise in the activity of low-Km cyclic-AMP phosphodiesterase activity in atheromatous lesions and adjacent muscular layers, especially in rabbits with rapidly progressing atheroma.", "contents": "Hyperreactive arterial endothelial cells: a clue for the treatment of atherosclerosis. Arterial endothelial cells, which are capable of phagocytizing carbon particles of the same size as beta- and pre-beta-lipoprotein, were found only in endothelial cells of arterial segments susceptible to atheromatous changes in susceptible animal species, and the distribution closely corresponded to the susceptibility. The distribution of such endothelial cells is dense in large arteries, in the openings to their branches, especially in downstream portions, of rabbits, hens, and cocks; however, the distribution is relatively scanty in arteries of rhesus monkeys and is very scanty in dogs. Carbon particles were also rare in the suckling rabbit and tended to increase with age. They were not found in Wistar rats but were found in spontaneously hypertensive rats, which showed a characteristically diffuse distribution, even in relatively small arteries. The carbon particles, phagocytized, were released to the subendothelial space but were difficult to pass through the internal elastic lamina and tended to stagnate there for more than one month. The authors therefore call these cells hyperreactive endothelial cells. Various vasoactive substances, such as angiotensin II, histamine, and serotonin, significantly enhanced the phagocytic activities of arotic endothelial cells in rabbits; epinephrine and norepinephrine also slightly enhanced these activities. Various smooth muscle relaxants, such as ATP, pyridinol carbamate (ATP synthesis-enhancing substance), cycli-AMP, dibutyryl cycli-AMP, phthalazinol (cyclic-AMP phosphodiesterase inhibitor), iproveratril (calcium entry-inhibiting substance), colchicine, and vinblastine, with their different modes of action, commonly inhibited phagocytic activities, a finding that suggests a significant role for contractile protein in the permeability problem of atherogenesis. The atheromatous lesions of cholesterol-fed rabbits exhibited a striking increase in hyperreactive endothelial cells, accompanied by a marked rise in the activity of low-Km cyclic-AMP phosphodiesterase activity in atheromatous lesions and adjacent muscular layers, especially in rabbits with rapidly progressing atheroma."}
{"id": "PMID:188373", "title": "Plasma, red cell and cerebrospinal fluid concentrations of mannitol and sorbital in patients with severe chronic renal failure.", "content": "The concentrations of mannitol and sorbitol in plasma, red cells, cerebrospinal fluid and urine were determined in 24 patients with chronic renal failure; 10 of them were on conservative treatment and 14 were haemodialysed three times weekly. The mannitol concentration was significantly increased in the plasma and the cerebrospinal fluid of the uraemic patients compared with the controls. In six out of ten uraemic patients mannitol clearance values exceeded creatinine clearance values. The plasma concentration of sorbitol was undetectable or very low in all patients and control subjects. Red-cell and cerebrospinal fluid concentrations of sorbitol showed a large individual variation in the uraemic patients on conservative treatment and did not correlate with kidney function. During dialysis the mannitol concentration decreased, leading to a small osmotic gradient between the plasma and the red cells. The changes in the concentration of mannitol during dialysis showed no connection with the symptoms of central nervous disturbance which appeared during dialysis treatment. The red cell sorbitol concentration during dialysis increased by about 20%. There was a correlation (p less than 0.05) between t,e increase in sorbital in cereemic patients.", "contents": "Plasma, red cell and cerebrospinal fluid concentrations of mannitol and sorbital in patients with severe chronic renal failure. The concentrations of mannitol and sorbitol in plasma, red cells, cerebrospinal fluid and urine were determined in 24 patients with chronic renal failure; 10 of them were on conservative treatment and 14 were haemodialysed three times weekly. The mannitol concentration was significantly increased in the plasma and the cerebrospinal fluid of the uraemic patients compared with the controls. In six out of ten uraemic patients mannitol clearance values exceeded creatinine clearance values. The plasma concentration of sorbitol was undetectable or very low in all patients and control subjects. Red-cell and cerebrospinal fluid concentrations of sorbitol showed a large individual variation in the uraemic patients on conservative treatment and did not correlate with kidney function. During dialysis the mannitol concentration decreased, leading to a small osmotic gradient between the plasma and the red cells. The changes in the concentration of mannitol during dialysis showed no connection with the symptoms of central nervous disturbance which appeared during dialysis treatment. The red cell sorbitol concentration during dialysis increased by about 20%. There was a correlation (p less than 0.05) between t,e increase in sorbital in cereemic patients."}
{"id": "PMID:188374", "title": "The effect of segmental epidural analgesia on maternal ACTH, cortisol and TSH during labour.", "content": "Maternal plasma ACTH, cortisol and TSH concentrations were determined during the course of the induced labours of 20 normal parturients. Alternate mothers were given segmental epidural analgesia for pain relief during the first stage of labour. The remaining parturients served as controls. The ACTH level rose in same way in both groups, reaching its peak at the moment of delivery and decreasing rapidly thereafter. Cortisol secretion reached its maximum during the first stage of labour in the moment of delivery. After delivery the cortisol level decreased more rapidly in the epidural group tha. in the control gro,p. Umbilical venous cortisol concentration was the same in both groups. The maternal TSH level did not change significantly during labour in either group.", "contents": "The effect of segmental epidural analgesia on maternal ACTH, cortisol and TSH during labour. Maternal plasma ACTH, cortisol and TSH concentrations were determined during the course of the induced labours of 20 normal parturients. Alternate mothers were given segmental epidural analgesia for pain relief during the first stage of labour. The remaining parturients served as controls. The ACTH level rose in same way in both groups, reaching its peak at the moment of delivery and decreasing rapidly thereafter. Cortisol secretion reached its maximum during the first stage of labour in the moment of delivery. After delivery the cortisol level decreased more rapidly in the epidural group tha. in the control gro,p. Umbilical venous cortisol concentration was the same in both groups. The maternal TSH level did not change significantly during labour in either group."}
{"id": "PMID:188375", "title": "The regulation of heme biosynthesis.", "content": "Changes in the levels of the heme biosynthetic enzymes were studied in cells and protoplasts of Saccharomyces cerevisiae during glucose derepression and respiratory adaptation. On aerobic or anaerobic glucose derepression or in the presence of 3', 5' cyclic AMP the levels of beta-aminolevulinic acid dehydratase, protoporphyrinogen oxidase and ferrochelatase increased whereas the levels of the enzymes catalysing the reactions from porphobilinogen to protoporphyrinogen IX remained constant. In contrast, the level of beta-aminolevulinic acid synthetase decreased during aerobic glucose derepression and in the presence of 3', 5' cyclic AMP, but it remained unchanged during anaerobic derepression. The heme content of the cells increased during aerobic glucose derepression but no increase was observed during anaerobic derepression of the cells. It is concluded that, in yeast, the inhibitory effect of anaerobiosis on heme synthesis is due, at least in part, to the requirement for oxygen in the oxidation of protoporphyrinogen IX, and that the effect of glucose on heme biosynthesis is mediated via glucose repression of protoporphyrinogen oxidase and possibly ferrochelatase.", "contents": "The regulation of heme biosynthesis. Changes in the levels of the heme biosynthetic enzymes were studied in cells and protoplasts of Saccharomyces cerevisiae during glucose derepression and respiratory adaptation. On aerobic or anaerobic glucose derepression or in the presence of 3', 5' cyclic AMP the levels of beta-aminolevulinic acid dehydratase, protoporphyrinogen oxidase and ferrochelatase increased whereas the levels of the enzymes catalysing the reactions from porphobilinogen to protoporphyrinogen IX remained constant. In contrast, the level of beta-aminolevulinic acid synthetase decreased during aerobic glucose derepression and in the presence of 3', 5' cyclic AMP, but it remained unchanged during anaerobic derepression. The heme content of the cells increased during aerobic glucose derepression but no increase was observed during anaerobic derepression of the cells. It is concluded that, in yeast, the inhibitory effect of anaerobiosis on heme synthesis is due, at least in part, to the requirement for oxygen in the oxidation of protoporphyrinogen IX, and that the effect of glucose on heme biosynthesis is mediated via glucose repression of protoporphyrinogen oxidase and possibly ferrochelatase."}
{"id": "PMID:188376", "title": "Studies on heme synthesis in the rat adrenal.", "content": "The activity and regulation of rat adrenal delta-aminolevulinic acid synthetase (EC 2.3.1.37) has been studied. The activity of delta-aminolevulinic acid synthetase in  rat adrenal homogenates is comparable to the activity found in rat hepatic homogenates when untreated animals are employed. Starvation of rats for 24 and 48 hours increased adrenal delta-aminolevulinic acid synthetase activity without altering the hepatic enzyme. The treatment of rats with ACTH gel also increased adrenal delta-aminolevulinic acid synthetase activity. The effect of starvation on rat adrenal delta-aminolevulinic acid synthetase activity appears to be mediated by ACTH and can be prevented by the administration of dexamethasone. Adrenal delta-aminolevulinic acid synthetase appears to be refractory to induction by agents which induce the hepatic enzyme. These results suggest that the adrenal enzyme may be uniquely controlled by neural and endocrine influences which differ from the factors which regulate the activity of the hepatic enzyme.", "contents": "Studies on heme synthesis in the rat adrenal. The activity and regulation of rat adrenal delta-aminolevulinic acid synthetase (EC 2.3.1.37) has been studied. The activity of delta-aminolevulinic acid synthetase in  rat adrenal homogenates is comparable to the activity found in rat hepatic homogenates when untreated animals are employed. Starvation of rats for 24 and 48 hours increased adrenal delta-aminolevulinic acid synthetase activity without altering the hepatic enzyme. The treatment of rats with ACTH gel also increased adrenal delta-aminolevulinic acid synthetase activity. The effect of starvation on rat adrenal delta-aminolevulinic acid synthetase activity appears to be mediated by ACTH and can be prevented by the administration of dexamethasone. Adrenal delta-aminolevulinic acid synthetase appears to be refractory to induction by agents which induce the hepatic enzyme. These results suggest that the adrenal enzyme may be uniquely controlled by neural and endocrine influences which differ from the factors which regulate the activity of the hepatic enzyme."}
{"id": "PMID:188377", "title": "[Dissociation between the effects of TSH and dibutyryl cAMP on thyroxine secretion by isolated thyroid cells. Similarity of actions on iodide uptake and thyroxine synthesis (author's transl)].", "content": "We have compared the effects of TSH and dibutyryl-cAMP (DBC) on three parameters of iodine metabolism in isolated hog thyroid cells: iodide uptake, thyroxine (T4) synthesis and T4 secretion. As WILSON, we observed a similarity between TSH (60 mU/ml) and DBC (3 mM) actions on iodide uptake and T4 synthesis. But DBC did not reproduce the TSH stimulation of T4 secretion. Since TSH increased T4 secretion in the presence of DBC, the lack of effect of DBC was not due to an alteration of the secretory process by DBC. The present observation might suggest that the stimulatory effect of TSH on T4 secretion by isolated thyroid cells is not mediated by the adenyl cyclase-cAMP system, or could indicate that DBC may not act like cAMP on some target enzyme systems.", "contents": "[Dissociation between the effects of TSH and dibutyryl cAMP on thyroxine secretion by isolated thyroid cells. Similarity of actions on iodide uptake and thyroxine synthesis (author's transl)]. We have compared the effects of TSH and dibutyryl-cAMP (DBC) on three parameters of iodine metabolism in isolated hog thyroid cells: iodide uptake, thyroxine (T4) synthesis and T4 secretion. As WILSON, we observed a similarity between TSH (60 mU/ml) and DBC (3 mM) actions on iodide uptake and T4 synthesis. But DBC did not reproduce the TSH stimulation of T4 secretion. Since TSH increased T4 secretion in the presence of DBC, the lack of effect of DBC was not due to an alteration of the secretory process by DBC. The present observation might suggest that the stimulatory effect of TSH on T4 secretion by isolated thyroid cells is not mediated by the adenyl cyclase-cAMP system, or could indicate that DBC may not act like cAMP on some target enzyme systems."}
{"id": "PMID:188378", "title": "[Variation of plasmatic adenosine 3'', 5-cyclic monophosphate in irradiated-enterectomised dogs (author's transl)].", "content": "In the irradiated dog at different doses 250-400 R., a level plasma AMPc rise has been shown since the fourth hour with a maximum at 24 hours, returning to normal values about the thirtieth day. In irradiated at 250-300 R and secondarily enterectomised animals, nucleotide level rises 24 hours later, however this phenomenon is less intensive and later irradiated at 350 and 400 R.", "contents": "[Variation of plasmatic adenosine 3'', 5-cyclic monophosphate in irradiated-enterectomised dogs (author's transl)]. In the irradiated dog at different doses 250-400 R., a level plasma AMPc rise has been shown since the fourth hour with a maximum at 24 hours, returning to normal values about the thirtieth day. In irradiated at 250-300 R and secondarily enterectomised animals, nucleotide level rises 24 hours later, however this phenomenon is less intensive and later irradiated at 350 and 400 R."}
{"id": "PMID:188379", "title": "[Defect of growth hormone receptors in hereditary hypopituitary dwarf mice (author's transl)].", "content": "The binding of 125I-growth hormone to its specific receptors was comparatively studied in liver cells isolated from dwarf mice and littermates. The specific binding of growth hormone was about eight-fold lower in cells from dwarf mice than in those from littermates. However, the specific binding of insulin, although lower, was not significantly modified in dwarf as compared to littermates. The defect of growth hormone receptors in hypopituitary dwarf mice is likely to be related to the lack of hormonal effect in this animal when the growth hormone was administered alone.", "contents": "[Defect of growth hormone receptors in hereditary hypopituitary dwarf mice (author's transl)]. The binding of 125I-growth hormone to its specific receptors was comparatively studied in liver cells isolated from dwarf mice and littermates. The specific binding of growth hormone was about eight-fold lower in cells from dwarf mice than in those from littermates. However, the specific binding of insulin, although lower, was not significantly modified in dwarf as compared to littermates. The defect of growth hormone receptors in hypopituitary dwarf mice is likely to be related to the lack of hormonal effect in this animal when the growth hormone was administered alone."}
{"id": "PMID:188384", "title": "\"Phoenix phenomenon\" in the growth of Clostridium perfringens.", "content": "The \"Phoenix phenomenon\" was observed with Clostridium perfringens Hobbs' serological type 9 (HT9) in a cooked-meat medium at 81.7 degrees C by a decrease in plate count (phase I), followed by an increase in count to the intiial level (phase II) and a continued increase above the initial count (phase III). The effects of sporulation, age of inoculum, assay medium, anaerobiosis, diluent, and growth inhibitor were studied. This phenomenon was reproduced in experiments with sporulation-negative mutants derived from HT9 inocula of various cell ages, and different assay media (sulfite-iron agar, tryptose-soytone-yeast extract agar, prereduced peptone-yeast extract agar, prereduced veal agar, and veal agar). When strict anaerobic conditions were employed, it was necessary to increase the heating temperature to 52.3 degrees C to observe the phenomenon. The phenomenon was eliminated at 52.3 degrees C when a combination of strict anaerobic conditions, prereduced media, and prereduced veal diluent was employed. The addition of nalidixic acid at the minimum point of the growth curve (end of phase I) had no effect on the appearance of phase II; however, phase III was completely inhibited. This indicated that phases I and II were an injury-recovery process.", "contents": "\"Phoenix phenomenon\" in the growth of Clostridium perfringens. The \"Phoenix phenomenon\" was observed with Clostridium perfringens Hobbs' serological type 9 (HT9) in a cooked-meat medium at 81.7 degrees C by a decrease in plate count (phase I), followed by an increase in count to the intiial level (phase II) and a continued increase above the initial count (phase III). The effects of sporulation, age of inoculum, assay medium, anaerobiosis, diluent, and growth inhibitor were studied. This phenomenon was reproduced in experiments with sporulation-negative mutants derived from HT9 inocula of various cell ages, and different assay media (sulfite-iron agar, tryptose-soytone-yeast extract agar, prereduced peptone-yeast extract agar, prereduced veal agar, and veal agar). When strict anaerobic conditions were employed, it was necessary to increase the heating temperature to 52.3 degrees C to observe the phenomenon. The phenomenon was eliminated at 52.3 degrees C when a combination of strict anaerobic conditions, prereduced media, and prereduced veal diluent was employed. The addition of nalidixic acid at the minimum point of the growth curve (end of phase I) had no effect on the appearance of phase II; however, phase III was completely inhibited. This indicated that phases I and II were an injury-recovery process."}
{"id": "PMID:188383", "title": "Effect of ribavirin on murine cytomegalovirus infection.", "content": "Ribavirin (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide), a new synthetic nucleoside, inhibited murine cytomegalovirus in cell culture. This was shown by the inhibition of viral cytopathic effect and plaque formation, as well as reduction in the yield of virus. Despite this in vitro antiviral effect, ribavirin did not protect mice from mortality produced by a high inoculum of cytomegalovirus. When a lower inoculum was used to initiate a chronic infection, the administration of ribavirin for 9 days had no effect on the titer of cytomegalovirus in the salivary gland, kidney, liver, and spleen. Thus, ribavirin was ineffective in the treatment of both acute and chronic murine cytomegalovirus infections.", "contents": "Effect of ribavirin on murine cytomegalovirus infection. Ribavirin (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide), a new synthetic nucleoside, inhibited murine cytomegalovirus in cell culture. This was shown by the inhibition of viral cytopathic effect and plaque formation, as well as reduction in the yield of virus. Despite this in vitro antiviral effect, ribavirin did not protect mice from mortality produced by a high inoculum of cytomegalovirus. When a lower inoculum was used to initiate a chronic infection, the administration of ribavirin for 9 days had no effect on the titer of cytomegalovirus in the salivary gland, kidney, liver, and spleen. Thus, ribavirin was ineffective in the treatment of both acute and chronic murine cytomegalovirus infections."}
{"id": "PMID:188380", "title": "[Alteration of the catecholamine receptor during hepatic malignancy (author's transl)].", "content": "The adenylate cyclase system of a plasma membrane preparation from normal rat liver responds to various catecholamines in the following order: protokylol greater than isoproterenol greater than epinephrine greater than norepinephrine. In the Zadejela ascites hepatoma, the order of sensitivity is modified, indicating a transformation of the receptor from the beta2 to the beta1 type. These observations suggest that the catecholamine receptor might be a single entity, susceptible to secondary, and reversible, modification towards either a beta 1 or a beta 2 type.", "contents": "[Alteration of the catecholamine receptor during hepatic malignancy (author's transl)]. The adenylate cyclase system of a plasma membrane preparation from normal rat liver responds to various catecholamines in the following order: protokylol greater than isoproterenol greater than epinephrine greater than norepinephrine. In the Zadejela ascites hepatoma, the order of sensitivity is modified, indicating a transformation of the receptor from the beta2 to the beta1 type. These observations suggest that the catecholamine receptor might be a single entity, susceptible to secondary, and reversible, modification towards either a beta 1 or a beta 2 type."}
{"id": "PMID:188381", "title": "[Variations in the estradiol and progesterone receptors in human endometrium during the menstrual cycle].", "content": "The concentration of estradiol and progesterone \"receptors\", both cytoplasmic and nuclear, has been measured in human endometrium during the menstrual cycle using an exchange assay method. A rapid increase of the concentration of the two \"receptors\" has been observed during the proliferative phase followed by a striking decrease during the secretory phase. New physiological and pharmacological aspects may be derived from these results.", "contents": "[Variations in the estradiol and progesterone receptors in human endometrium during the menstrual cycle]. The concentration of estradiol and progesterone \"receptors\", both cytoplasmic and nuclear, has been measured in human endometrium during the menstrual cycle using an exchange assay method. A rapid increase of the concentration of the two \"receptors\" has been observed during the proliferative phase followed by a striking decrease during the secretory phase. New physiological and pharmacological aspects may be derived from these results."}
{"id": "PMID:188385", "title": "Dapsone-induced peripheral neuropathy.", "content": "Peripheral neuropathy occurred in a 32-year-old man who was receiving dapsone (Aviosulfon) for dermatitis herpetiformis. Neurological examination showed polyneuropathy that involved the median and ulnar nerves, with a lesser involvement of other peripheral nerves. After treatment with dapsone was discontinued, the neuropathy reversed itself, with practically complete return of function of all nerves involved.", "contents": "Dapsone-induced peripheral neuropathy. Peripheral neuropathy occurred in a 32-year-old man who was receiving dapsone (Aviosulfon) for dermatitis herpetiformis. Neurological examination showed polyneuropathy that involved the median and ulnar nerves, with a lesser involvement of other peripheral nerves. After treatment with dapsone was discontinued, the neuropathy reversed itself, with practically complete return of function of all nerves involved."}
{"id": "PMID:188382", "title": "Cyclic AMP and T-cell differentiation.", "content": "We have studied the effects of a circulating thymic factor (TF), cyclic AMP (cAMP) and prostaglandins on T-lymphocyte differentiation in the mouse using three parameters: 1) 0-bearing cell percentage evaluated by a cytotoxicity test with anti-0 serum (A0S) plus complement; 2) 0-antigen presence on rosette forming cells (RFC) assessed by the inhibition of rosette formation with A0S; 3) lymphocyte mediated cytotoxicity (LMC) against allogeneic target cells after in vivo sensitization, using a chromium release assay.", "contents": "Cyclic AMP and T-cell differentiation. We have studied the effects of a circulating thymic factor (TF), cyclic AMP (cAMP) and prostaglandins on T-lymphocyte differentiation in the mouse using three parameters: 1) 0-bearing cell percentage evaluated by a cytotoxicity test with anti-0 serum (A0S) plus complement; 2) 0-antigen presence on rosette forming cells (RFC) assessed by the inhibition of rosette formation with A0S; 3) lymphocyte mediated cytotoxicity (LMC) against allogeneic target cells after in vivo sensitization, using a chromium release assay."}
{"id": "PMID:188386", "title": "Psychoendocrinological studies in dwarfed children and adolescents.", "content": "Thirty-two dwarfed children and adolescents were studied clinically, by laboratory assessment, by a battery of psychological tests and a structured interview. Growth hormone deficiency was present in 16 cases, but in the remaining 16 cases there was no endocrine disease. Dwarfed children differed from nornal controls in perception, and a specific personality pattern emerged in the dwarfed children. The effects of age, sex, and socioeconomic status on personality traits were similar for dwarfs as for controls. Intelligence and personality variable were similar in dwarfs with and without endocrine disease. However, symptoms of the psychoendocrine syndrome, namely appetite and thirst disturbances, hypersensitivities, and impulse reduction, were more frequently seen among hypopituitary dwarfs. Social and coping behaviour was impaired in the majority of dwarfs. It is concluded that psychological disturbance occuring inchildren of small stature is a response to being small and is not attributable to any endocrine effect.", "contents": "Psychoendocrinological studies in dwarfed children and adolescents. Thirty-two dwarfed children and adolescents were studied clinically, by laboratory assessment, by a battery of psychological tests and a structured interview. Growth hormone deficiency was present in 16 cases, but in the remaining 16 cases there was no endocrine disease. Dwarfed children differed from nornal controls in perception, and a specific personality pattern emerged in the dwarfed children. The effects of age, sex, and socioeconomic status on personality traits were similar for dwarfs as for controls. Intelligence and personality variable were similar in dwarfs with and without endocrine disease. However, symptoms of the psychoendocrine syndrome, namely appetite and thirst disturbances, hypersensitivities, and impulse reduction, were more frequently seen among hypopituitary dwarfs. Social and coping behaviour was impaired in the majority of dwarfs. It is concluded that psychological disturbance occuring inchildren of small stature is a response to being small and is not attributable to any endocrine effect."}
{"id": "PMID:188387", "title": "Screening for familial hyper-beta-lipoproteinaemia in children in hospital.", "content": "1510 plasma cholesterol estimations were made in 1391 children admitted to hospital as part of a biochemical profile. Babies under 1 year and children known to have familial hyperlipoproteinaemia were excluded. The mean concentration was 4-28 mmol/l +/- 1-04 (1 SD) (165-3 mg/100 ml +/- 38-6), and levels exceeded 5-93 mmol/l (229 mg/100 ml) in 68 children. Repeat estimations on 55 of these children showed 34 still to have values greater than 5-93 mmol/l and family studies were performed in 19 of these. In 8 children hypercholesterolaemia was secondary and no familial lipoprotein disorder was present. Familial hyper-beta-lipoproteinaemia (FH) was diagnosed in 3 children and in 2 of the families there was a history of early ischaemic heart disease. In 2 children the diagnosis was in doubt. In the remaining 6 children FH and secondary hyperlipoproteinaemia were excluded so the hypercholesterolaemia was presumably environmentally induced, possibly in association with polygenic inheritance. In the present state of knowledge screening of the childhood population for FH by means of plasma cholesterol determinations cannot be recommended. Studies of lipoproteins should, however, be made in children from families known to have FH or early coronary heart disease.", "contents": "Screening for familial hyper-beta-lipoproteinaemia in children in hospital. 1510 plasma cholesterol estimations were made in 1391 children admitted to hospital as part of a biochemical profile. Babies under 1 year and children known to have familial hyperlipoproteinaemia were excluded. The mean concentration was 4-28 mmol/l +/- 1-04 (1 SD) (165-3 mg/100 ml +/- 38-6), and levels exceeded 5-93 mmol/l (229 mg/100 ml) in 68 children. Repeat estimations on 55 of these children showed 34 still to have values greater than 5-93 mmol/l and family studies were performed in 19 of these. In 8 children hypercholesterolaemia was secondary and no familial lipoprotein disorder was present. Familial hyper-beta-lipoproteinaemia (FH) was diagnosed in 3 children and in 2 of the families there was a history of early ischaemic heart disease. In 2 children the diagnosis was in doubt. In the remaining 6 children FH and secondary hyperlipoproteinaemia were excluded so the hypercholesterolaemia was presumably environmentally induced, possibly in association with polygenic inheritance. In the present state of knowledge screening of the childhood population for FH by means of plasma cholesterol determinations cannot be recommended. Studies of lipoproteins should, however, be made in children from families known to have FH or early coronary heart disease."}
{"id": "PMID:188388", "title": "Stimulation by melanocyte stimulating hormone and dibutyryl adenosine 3'5'-cyclic monophosphate of DNA synthesis in human melanocytes in vitro.", "content": "The proliferation of human melanocytes in vitro was stimulated by MSH. This stimulation was further intensified by the simultaneous addition of theophylline with MSH. Theophylline alone stimulated proliferation moderately. Dibutyryl cyclic AMP strongly stimulated the proliferation, but sodium butyrate, 5'-AMP and cGMP did not. The stimulation by dibutyryl cyclic AMP was continued up to 4 days so far tested. These findings are directly opposed to those on mouse melanoma cells in culture which responded with retarded growth to MSH and cyclic AMP. It is suggested that the difference of proliferation control may explain the different reaction of the melanocyte and the melanoma cells. The epidermal melanocytes seem to belong to the exceptional group of the cells which responded to cyclic AMP with accelerated proliferation.", "contents": "Stimulation by melanocyte stimulating hormone and dibutyryl adenosine 3'5'-cyclic monophosphate of DNA synthesis in human melanocytes in vitro. The proliferation of human melanocytes in vitro was stimulated by MSH. This stimulation was further intensified by the simultaneous addition of theophylline with MSH. Theophylline alone stimulated proliferation moderately. Dibutyryl cyclic AMP strongly stimulated the proliferation, but sodium butyrate, 5'-AMP and cGMP did not. The stimulation by dibutyryl cyclic AMP was continued up to 4 days so far tested. These findings are directly opposed to those on mouse melanoma cells in culture which responded with retarded growth to MSH and cyclic AMP. It is suggested that the difference of proliferation control may explain the different reaction of the melanocyte and the melanoma cells. The epidermal melanocytes seem to belong to the exceptional group of the cells which responded to cyclic AMP with accelerated proliferation."}
{"id": "PMID:188389", "title": "Xanthoma secondary to reticulo-histiocyte infiltration.", "content": "Three cases of xanthomas occurring secondarily are reported: The primary dermatoses were erythroderma, actinic reticuloid and histiocytosis X. Although a slight elevation of pre-beta-lipoprotein was recognized, xanthomas occurring in these particular 3 cases were assumed to be due to the proliferation or hyperplasia of reticulohistiocytes in the skin. The foam cells found in the xanthoma case with erythroderma and actinic reticuloid appeared different from those with histiocytosis X in their fine structures. The lipid constituents of the xanthoma lesion were found to be quite dissimilar from those of serum lipids.", "contents": "Xanthoma secondary to reticulo-histiocyte infiltration. Three cases of xanthomas occurring secondarily are reported: The primary dermatoses were erythroderma, actinic reticuloid and histiocytosis X. Although a slight elevation of pre-beta-lipoprotein was recognized, xanthomas occurring in these particular 3 cases were assumed to be due to the proliferation or hyperplasia of reticulohistiocytes in the skin. The foam cells found in the xanthoma case with erythroderma and actinic reticuloid appeared different from those with histiocytosis X in their fine structures. The lipid constituents of the xanthoma lesion were found to be quite dissimilar from those of serum lipids."}
{"id": "PMID:188390", "title": "[Behaviour of collagen peptidase in the serum of patients with progressive systemic sclerosis during gestagen therapy (author's transl)].", "content": "In 20 patients with progressive systemic sclerosis the activity of collagen peptidase in serum before and after gestagen therapy of 10 resp. 20 days was determined. After 20 days the enzyme activity was significantly decreased. These findings show no correlation to the known gestagen induced alterations of the collagen metabolism.", "contents": "[Behaviour of collagen peptidase in the serum of patients with progressive systemic sclerosis during gestagen therapy (author's transl)]. In 20 patients with progressive systemic sclerosis the activity of collagen peptidase in serum before and after gestagen therapy of 10 resp. 20 days was determined. After 20 days the enzyme activity was significantly decreased. These findings show no correlation to the known gestagen induced alterations of the collagen metabolism."}
{"id": "PMID:188391", "title": "Tumor vascularity as a prognostic factor for hepatic tumors.", "content": "The prognostic and therapeutic significance of tumor vascularity was studied in 36 patients with hepatoma or metastatic colon cancer in the liver. All patients had nonresectable tumor and were treated by hepatic artery ligation and hepatic arterial infusion chemotherapy. Chemotherapy consisted of methotrexate, actinomycin-D, 5-fluorouracil and cyclophosphamide. Hepatic tumors were categorized into Grades I to III in the order of increasing vascularity as determined by preoperative hepatic angiography. Tumor vascularity of 15 patients with hepatoma was Grade III in 11 (73%) and Grade II in 4 (27%). No patient with hepatoma had a Grade I tumor. The median survival of patients was 10 and 6 months for Grade III and II hepatomas, respectively, after hepatic artery ligation, and 18 and 8.5 months for Grade III and II, respectively, from the time of diagnosis of hepatoma. Tumor vascularity of 21 patients with metastatic colon cancer was as follows: Grade III in 3 (14%); Grade II in 10 (48%); and Grade I in 8 (38%). The median survival was 11, 10.5 and 4 months for Grades III, II and I, respectively, after hepatic artery ligation, and 17, 14.5 and 7.2 months for Grades III, II and I, respectively, from the time of diagnosis of hepatic metastases of colon cancer. The results indicate that the more vascular the hepatic tumor on angiogram, the better the prognosis following hepatic artery ligation and infusional chemotherapy.", "contents": "Tumor vascularity as a prognostic factor for hepatic tumors. The prognostic and therapeutic significance of tumor vascularity was studied in 36 patients with hepatoma or metastatic colon cancer in the liver. All patients had nonresectable tumor and were treated by hepatic artery ligation and hepatic arterial infusion chemotherapy. Chemotherapy consisted of methotrexate, actinomycin-D, 5-fluorouracil and cyclophosphamide. Hepatic tumors were categorized into Grades I to III in the order of increasing vascularity as determined by preoperative hepatic angiography. Tumor vascularity of 15 patients with hepatoma was Grade III in 11 (73%) and Grade II in 4 (27%). No patient with hepatoma had a Grade I tumor. The median survival of patients was 10 and 6 months for Grade III and II hepatomas, respectively, after hepatic artery ligation, and 18 and 8.5 months for Grade III and II, respectively, from the time of diagnosis of hepatoma. Tumor vascularity of 21 patients with metastatic colon cancer was as follows: Grade III in 3 (14%); Grade II in 10 (48%); and Grade I in 8 (38%). The median survival was 11, 10.5 and 4 months for Grades III, II and I, respectively, after hepatic artery ligation, and 17, 14.5 and 7.2 months for Grades III, II and I, respectively, from the time of diagnosis of hepatic metastases of colon cancer. The results indicate that the more vascular the hepatic tumor on angiogram, the better the prognosis following hepatic artery ligation and infusional chemotherapy."}
{"id": "PMID:188392", "title": "Ectopic ACTH syndrome due to salivary gland adenoid cystic carcinoma.", "content": "A 68-year-old woman developed Cushing syndrome associated with a submaxillary salivary gland adenoid cystic carcinoma. High levels of immunoreactive adrenocorticotrophic hormone (ACTH) were found in the tumor and peripheral blood. Urinary 17-hydroxycorticosteroid levels decreased following administration of dexamethasone, suggesting possible suppression of ectopic ACTH production. however, there was no specific in vitro binding of dexamethasone by tumor cytosol. A trial of metyrapone therapy resulted in control of hypokalemia and hyperglycemia. Both plasma cortisol and 11-deoxycortisol levels decreased with metyrapone administration, suggesting that this agent may inhibit not only 11-beta-hydroxylation, but also possibly earlier steps in glucocorticoid synthesis.", "contents": "Ectopic ACTH syndrome due to salivary gland adenoid cystic carcinoma. A 68-year-old woman developed Cushing syndrome associated with a submaxillary salivary gland adenoid cystic carcinoma. High levels of immunoreactive adrenocorticotrophic hormone (ACTH) were found in the tumor and peripheral blood. Urinary 17-hydroxycorticosteroid levels decreased following administration of dexamethasone, suggesting possible suppression of ectopic ACTH production. however, there was no specific in vitro binding of dexamethasone by tumor cytosol. A trial of metyrapone therapy resulted in control of hypokalemia and hyperglycemia. Both plasma cortisol and 11-deoxycortisol levels decreased with metyrapone administration, suggesting that this agent may inhibit not only 11-beta-hydroxylation, but also possibly earlier steps in glucocorticoid synthesis."}
{"id": "PMID:188393", "title": "Liver disease in renal transplant recipients.", "content": "Significant liver disease developed in 14 patients after renal transplantation. Nine patients had morphologic and functional evidence of chronic active hepatitis. In general, these patients had few symptoms of liver disease, even though the course of chronic active hepatitis was progressive. Despite large doses of prednisone, cirrhosis ultimately developed in five patients. The cause of chronic active hepatitis could not be related to azathioprine or methyldopa therapy because there was no perceptible change in the course of liver disease after treatment with these drugs was stopped. Three patients were persistently positive for hepatitis B surface antigen. Isolated instances of granulomatous hepatitis (Mycobacterium kansasii) and of prolonged intrahepatic cholestasis were encountered in patients with chronic active hepatitis. Two patients had acute cytomegalovirus hepatitis. There was one episode each of fulminant herpes simplex hepatitis and severe fatty metamorphosis.", "contents": "Liver disease in renal transplant recipients. Significant liver disease developed in 14 patients after renal transplantation. Nine patients had morphologic and functional evidence of chronic active hepatitis. In general, these patients had few symptoms of liver disease, even though the course of chronic active hepatitis was progressive. Despite large doses of prednisone, cirrhosis ultimately developed in five patients. The cause of chronic active hepatitis could not be related to azathioprine or methyldopa therapy because there was no perceptible change in the course of liver disease after treatment with these drugs was stopped. Three patients were persistently positive for hepatitis B surface antigen. Isolated instances of granulomatous hepatitis (Mycobacterium kansasii) and of prolonged intrahepatic cholestasis were encountered in patients with chronic active hepatitis. Two patients had acute cytomegalovirus hepatitis. There was one episode each of fulminant herpes simplex hepatitis and severe fatty metamorphosis."}
{"id": "PMID:188395", "title": "[Long-term follow-up of 128 children 13-14 years old, with birth weights of less than 2500 grams].", "content": "The records of 128 children, whose birth weight was below 2500 g and who were seen again at the ages of 13-14 years, were analyzed. Owing to the knowledge of the data of the last maternal menses in 115 cases, they could be separated in at-term dysmature, premature dysmature and true premature infants. The comparison between the 3 groups led to the following differences: On average, there is little difference between true premature infants and normal neonatal population, on both somatic and psychological points of view. Physical development is less satisfactory in at-term dysmature infants. If their median of I.Q. is close to normal, high intellectual abilities are rare and mental deficiency more frequent. In the physical, auditory, visual and psycho-motor fields, premature dysmature infants are the most underpriviliged.", "contents": "[Long-term follow-up of 128 children 13-14 years old, with birth weights of less than 2500 grams]. The records of 128 children, whose birth weight was below 2500 g and who were seen again at the ages of 13-14 years, were analyzed. Owing to the knowledge of the data of the last maternal menses in 115 cases, they could be separated in at-term dysmature, premature dysmature and true premature infants. The comparison between the 3 groups led to the following differences: On average, there is little difference between true premature infants and normal neonatal population, on both somatic and psychological points of view. Physical development is less satisfactory in at-term dysmature infants. If their median of I.Q. is close to normal, high intellectual abilities are rare and mental deficiency more frequent. In the physical, auditory, visual and psycho-motor fields, premature dysmature infants are the most underpriviliged."}
{"id": "PMID:188396", "title": "Murine leukemia induced by viral ultrafiltrates negative for XC plaque activity.", "content": "Leukemogenic activity has been encountered in 100 nm filtrates of a murine leukemia virus, PLLV-T2, associated with smaller than conventional C type particles. XC plaque assay of these filtrates gave negative results, revealing a lack of correlation between in vivo and in vitro activity. It is postulated that these filtrates contain viral subunits deficient for replication in BALB fibroblasts in vitro but able to transform lymphoid cells in vivo.", "contents": "Murine leukemia induced by viral ultrafiltrates negative for XC plaque activity. Leukemogenic activity has been encountered in 100 nm filtrates of a murine leukemia virus, PLLV-T2, associated with smaller than conventional C type particles. XC plaque assay of these filtrates gave negative results, revealing a lack of correlation between in vivo and in vitro activity. It is postulated that these filtrates contain viral subunits deficient for replication in BALB fibroblasts in vitro but able to transform lymphoid cells in vivo."}
{"id": "PMID:188397", "title": "ACTH-producing pheochromocytoma.", "content": "A benign adrenal medullary tumor that secreted adrenocorticotropic hormone (ACTH) was associated with bilateral adrenocortical hyperplasia and clinically evident Cushing syndrome. The clinical and chemical features were those usually associated with pituitary Cushing disease, including partial suppression of urinary OH steroids after administration of 8 mg of dexamethasone. The fractionization of the tumor's ACTH revealed 70% little \"biologically active\" ACTH, which is usually found in this concentration only in pituitary tissue.", "contents": "ACTH-producing pheochromocytoma. A benign adrenal medullary tumor that secreted adrenocorticotropic hormone (ACTH) was associated with bilateral adrenocortical hyperplasia and clinically evident Cushing syndrome. The clinical and chemical features were those usually associated with pituitary Cushing disease, including partial suppression of urinary OH steroids after administration of 8 mg of dexamethasone. The fractionization of the tumor's ACTH revealed 70% little \"biologically active\" ACTH, which is usually found in this concentration only in pituitary tissue."}
{"id": "PMID:188399", "title": "[The role of cysteine in cadmium- induced experimental testicular damage (author's transl)].", "content": "Simultaneous administration of cysteine and DL-ethionine in food protects, and enhances, respectively, the tissue damage produced by parenteral administration of cadmium (CdCl2) in testicles of rats. The effects are explained as an inactivation of SH-groups by cadmium, and in interference in cysteine metabolism by ethionine, respectively.", "contents": "[The role of cysteine in cadmium- induced experimental testicular damage (author's transl)]. Simultaneous administration of cysteine and DL-ethionine in food protects, and enhances, respectively, the tissue damage produced by parenteral administration of cadmium (CdCl2) in testicles of rats. The effects are explained as an inactivation of SH-groups by cadmium, and in interference in cysteine metabolism by ethionine, respectively."}
{"id": "PMID:188400", "title": "Effects of cadmium on carbonic anhydrase activity and hemoglobin content of rat testes.", "content": "The cadmilm-induced (Cd) damage of mammalian testes is thought to be correlated with an inhibition of carbonic anhydrase (CAH) by Cd. Since Cd causes dose-dependent changes in blood flow of the testes, an inhibition of CAH in the testes could be simulated by a decrease of CAH-rich erythrocytes. Therefore, CAH activities and hemoglobin (Hb) content were determined in blood and testes of untreated and Cd-treated Sprague-Dawley rats as well as in testes perfused via the testicular artery. Cd was intraperitoneally applied as CdCl2 in single doses of 1.5, 3.0, and 5.0 mg Cd2+/kg b.w., respectively. 1. The experiments on perfused testes clearly demonstrated that the CAH activities originate from erythrocytes rather than from a tissue located enzyme. 2. The alterations in blood circulation occurring shortly (0.25-1.0 h) after the Cd administration were characterized by a dose-dependent, transient decrease (1.5 mg Cd2+/kg) as well as an increase (3.0 and 5.0 mg Ck2+, respectively) of the Hb content in the testes. 3. Independent of these minor alterations in a later state (14-24 h after 1.5 mg Ck2+/kg, 7-14 h after 3.0 mg Cd2+/kg, and 1-3 after 5.0 mg Cd2+/kg), Cd induced the well known hemorrhagic alterations of the testes with a high increase of Hb content and CAH activity. 4. By means of the correlations between CAH activities and Hb content in blood and testes an inhibition of the CAH by Cd as the primary cause for the tissue damage of the testes could largely be excluded.", "contents": "Effects of cadmium on carbonic anhydrase activity and hemoglobin content of rat testes. The cadmilm-induced (Cd) damage of mammalian testes is thought to be correlated with an inhibition of carbonic anhydrase (CAH) by Cd. Since Cd causes dose-dependent changes in blood flow of the testes, an inhibition of CAH in the testes could be simulated by a decrease of CAH-rich erythrocytes. Therefore, CAH activities and hemoglobin (Hb) content were determined in blood and testes of untreated and Cd-treated Sprague-Dawley rats as well as in testes perfused via the testicular artery. Cd was intraperitoneally applied as CdCl2 in single doses of 1.5, 3.0, and 5.0 mg Cd2+/kg b.w., respectively. 1. The experiments on perfused testes clearly demonstrated that the CAH activities originate from erythrocytes rather than from a tissue located enzyme. 2. The alterations in blood circulation occurring shortly (0.25-1.0 h) after the Cd administration were characterized by a dose-dependent, transient decrease (1.5 mg Cd2+/kg) as well as an increase (3.0 and 5.0 mg Ck2+, respectively) of the Hb content in the testes. 3. Independent of these minor alterations in a later state (14-24 h after 1.5 mg Ck2+/kg, 7-14 h after 3.0 mg Cd2+/kg, and 1-3 after 5.0 mg Cd2+/kg), Cd induced the well known hemorrhagic alterations of the testes with a high increase of Hb content and CAH activity. 4. By means of the correlations between CAH activities and Hb content in blood and testes an inhibition of the CAH by Cd as the primary cause for the tissue damage of the testes could largely be excluded."}
{"id": "PMID:188401", "title": "Guanosine 3'-5'-monophosphate in the CSF of neurological patients.", "content": "Cyclic guanosine monophosphate (cGMP) levels have been measured in the cerebrospinal fluid of patients with various neurological diseases. The subjects with epilepsy or cerebrovascular diseases do not show any difference from the controls. Moreover, in the CSF of patients having cerebral tumors the levels of cGMP are markedly increased. This change is in line with previous in vitro studies on the increase of cGMP during cell growth and cell proliferation showing that the role of the nucleotide is important for the control of the life cycle of the cell.", "contents": "Guanosine 3'-5'-monophosphate in the CSF of neurological patients. Cyclic guanosine monophosphate (cGMP) levels have been measured in the cerebrospinal fluid of patients with various neurological diseases. The subjects with epilepsy or cerebrovascular diseases do not show any difference from the controls. Moreover, in the CSF of patients having cerebral tumors the levels of cGMP are markedly increased. This change is in line with previous in vitro studies on the increase of cGMP during cell growth and cell proliferation showing that the role of the nucleotide is important for the control of the life cycle of the cell."}
{"id": "PMID:188402", "title": "Pathogenesis of reovirus type 1 hydrocephalus in mice. Significance of aqueductal changes.", "content": "The pathogenesis of hydrocephalus following reovirus type 1 inoculation of neonatal mice has been examined by light microscopy, radiology, immunofluorescence, and electron microscopy. The reovirus infection causes an acute ependymitis and leptomeningitis, followed by a fibrous arachnoiditis and arachnoid villitis. Hydrocephalus develops in proportion to the degree of inflammatory/fibrotic changes within the cerebrospinal fluid pathways. With the beginning of hydrocephalus there is radiographic evidence of basal cistern blockage. As the hydrocephalic state progresses, axial herniation and compression of the midbrain result in the appearance of aqueduct stenosis. We demonstrate that the stenosis of the aqueduct is a secondary phenomenon, not causally related to the pathogenesis of hydrocephalus, and discuss the significance of this finding to human aqueduct stenosis.", "contents": "Pathogenesis of reovirus type 1 hydrocephalus in mice. Significance of aqueductal changes. The pathogenesis of hydrocephalus following reovirus type 1 inoculation of neonatal mice has been examined by light microscopy, radiology, immunofluorescence, and electron microscopy. The reovirus infection causes an acute ependymitis and leptomeningitis, followed by a fibrous arachnoiditis and arachnoid villitis. Hydrocephalus develops in proportion to the degree of inflammatory/fibrotic changes within the cerebrospinal fluid pathways. With the beginning of hydrocephalus there is radiographic evidence of basal cistern blockage. As the hydrocephalic state progresses, axial herniation and compression of the midbrain result in the appearance of aqueduct stenosis. We demonstrate that the stenosis of the aqueduct is a secondary phenomenon, not causally related to the pathogenesis of hydrocephalus, and discuss the significance of this finding to human aqueduct stenosis."}
{"id": "PMID:188398", "title": "[Hyperlipemias and obliterating peripheral arteriopathies].", "content": "160 patients suffering from radiologically confirmed peripheral obliterating arteriopathy have been studied with respect to frequency of lipid alterations. The resulting data were compared with those observed in a group of clinically healthy subjects. In the arteriopathic series, lipid alterations were encountered in 44% of patients, with a percentage of 12.5% for Fredrikson type II, 7.4% for III and 24% for IV. In women, incidence attained 50% and type classification was 25% for the 2nd, 12.5% for the 3rd and 14.5% for the 4th. An alteration of 18.7% was encountered in the control group. The high frequency of hyperlipidaemia in peripheral vascular diseases reported in the literature and confirmed by the above data, justifies the employement of appropriate dietetic and pharmacological measures for the prevention and treatment of this arteriosclerotic disease risk factor.", "contents": "[Hyperlipemias and obliterating peripheral arteriopathies]. 160 patients suffering from radiologically confirmed peripheral obliterating arteriopathy have been studied with respect to frequency of lipid alterations. The resulting data were compared with those observed in a group of clinically healthy subjects. In the arteriopathic series, lipid alterations were encountered in 44% of patients, with a percentage of 12.5% for Fredrikson type II, 7.4% for III and 24% for IV. In women, incidence attained 50% and type classification was 25% for the 2nd, 12.5% for the 3rd and 14.5% for the 4th. An alteration of 18.7% was encountered in the control group. The high frequency of hyperlipidaemia in peripheral vascular diseases reported in the literature and confirmed by the above data, justifies the employement of appropriate dietetic and pharmacological measures for the prevention and treatment of this arteriosclerotic disease risk factor."}
{"id": "PMID:188403", "title": "Skin punch biopsy in the diagnosis of juvenile neuronal ceroid-lipofuscinosis. A comparison with leukocyte peroxidase assay.", "content": "Electron microscopical examination of skin punch biopsy specimens was compared with the leukocyte peroxidase assay in establishing the diagnosis of juvenile neuronal ceroid-lipofuscinosis in three families with at least one affected child. Although the leukocyte peroxidase assay failed to distinguish between the patients, heterozygotes, and normal subjects, skin biopsy specimens containing characteristic cytosomes were found only in the children with this disease. In fact, in two families, the three affected members were identified by this method after the biopsy specimens had been randomized. Although only one to four cells containing such cytosomes were identified in each patient, not only cytosomes with curvilinear bodies but also those with rectilinear as well as \"fingerprint\" profiles were found. Thus, the skin punch biopsy appears to be a useful diagnostic aid the juvenile as well as the late infantile forms of neuronal ceroid-lipofuscinosis.", "contents": "Skin punch biopsy in the diagnosis of juvenile neuronal ceroid-lipofuscinosis. A comparison with leukocyte peroxidase assay. Electron microscopical examination of skin punch biopsy specimens was compared with the leukocyte peroxidase assay in establishing the diagnosis of juvenile neuronal ceroid-lipofuscinosis in three families with at least one affected child. Although the leukocyte peroxidase assay failed to distinguish between the patients, heterozygotes, and normal subjects, skin biopsy specimens containing characteristic cytosomes were found only in the children with this disease. In fact, in two families, the three affected members were identified by this method after the biopsy specimens had been randomized. Although only one to four cells containing such cytosomes were identified in each patient, not only cytosomes with curvilinear bodies but also those with rectilinear as well as \"fingerprint\" profiles were found. Thus, the skin punch biopsy appears to be a useful diagnostic aid the juvenile as well as the late infantile forms of neuronal ceroid-lipofuscinosis."}
{"id": "PMID:188405", "title": "Acetylcholine receptor protein. Neuromuscular transmission in immunized rabbits.", "content": "Rabbits injected with purified acetylcholine (ACh) receptor protein produce antibodies against the receptor and develop generalized muscle weakness. The compound muscle action potentials show a decremental fall in amplitude with repetitive nerve stimulation. Both the weakness and the decrement is counteracted by reversible cholinesterase inhibitors. Intracellular recordings from muscle endplates show that the amplitude of the miniature end-plate potentials is considerably reduced. A reduced binding of neurotoxin to muscles from immunized rabbits was observed. Nerve impulses release a normal number of ACh packages (quanta) from the motor nerve terminals. The muscle weakness in immunized rabbits thus has the same features as the muscle weakness in myasthenia gravis and may be a good animal model of myasthenia gravis.", "contents": "Acetylcholine receptor protein. Neuromuscular transmission in immunized rabbits. Rabbits injected with purified acetylcholine (ACh) receptor protein produce antibodies against the receptor and develop generalized muscle weakness. The compound muscle action potentials show a decremental fall in amplitude with repetitive nerve stimulation. Both the weakness and the decrement is counteracted by reversible cholinesterase inhibitors. Intracellular recordings from muscle endplates show that the amplitude of the miniature end-plate potentials is considerably reduced. A reduced binding of neurotoxin to muscles from immunized rabbits was observed. Nerve impulses release a normal number of ACh packages (quanta) from the motor nerve terminals. The muscle weakness in immunized rabbits thus has the same features as the muscle weakness in myasthenia gravis and may be a good animal model of myasthenia gravis."}
{"id": "PMID:188409", "title": "Erythrocyte enzyme activities in diploid and triploid salamanders (Pleurodeles waltlii) of both sexes.", "content": "Studies of several enzyme activities and of some metabolites in erythrocytes of the newt Pleurodels waltilii are described. The results indicate that differences exist between enzyme activities in males and females and in diploid and triploid animals. Females have higher erythrocyte enzyme activities than males. However, triploid animals have lower enzyme activites in their erythrocytes than diploid animals; this observation is more striking in females than in males.", "contents": "Erythrocyte enzyme activities in diploid and triploid salamanders (Pleurodeles waltlii) of both sexes. Studies of several enzyme activities and of some metabolites in erythrocytes of the newt Pleurodels waltilii are described. The results indicate that differences exist between enzyme activities in males and females and in diploid and triploid animals. Females have higher erythrocyte enzyme activities than males. However, triploid animals have lower enzyme activites in their erythrocytes than diploid animals; this observation is more striking in females than in males."}
{"id": "PMID:188410", "title": "Kinetic studies on [methionine sulphoxide] cytochrome c.", "content": "A cytochrome c haem ligand, methionine-80, was photo-oxidized to methionine sulphoxide and the subsequent changes in redox properties and ligand binding were monitored kinetically. Isoelectric focusing of the product showed the presence of a single oxidized species, capable of binding CO when reduced. The binding of CO to the reduced protein was followed in stopped-flow experiments, which revealed the presence of two binding processes, at neutral pH, with rate constants of K+1 = 3.4 X 10(3)M-1-S-1 and k+2 = 5.80 X 10(2)M-1-S-1. When CO was photolytically dissociated from the reduced protein two recombination processes were observed with rates almost identical with those observed in the stopped-flow experiments (k+1 = 3.3 X 10(3)M-1-S-1 and k+2 = 6.0 X 10(2)M-1-S-1). These findings provide evidence of two reduced forms of the protein. The reduction of [methionine sulphoxide]cytochrome c by Cr2+ at neutral pH in stopped-flow experiments showed the presence of a single second-order reduction process (k = 7.2 X 10(3)M-1-S-1, activation energy = 44kJ/mol) and one first-order process. This protein was compared with some other chemically modified cytochromes.", "contents": "Kinetic studies on [methionine sulphoxide] cytochrome c. A cytochrome c haem ligand, methionine-80, was photo-oxidized to methionine sulphoxide and the subsequent changes in redox properties and ligand binding were monitored kinetically. Isoelectric focusing of the product showed the presence of a single oxidized species, capable of binding CO when reduced. The binding of CO to the reduced protein was followed in stopped-flow experiments, which revealed the presence of two binding processes, at neutral pH, with rate constants of K+1 = 3.4 X 10(3)M-1-S-1 and k+2 = 5.80 X 10(2)M-1-S-1. When CO was photolytically dissociated from the reduced protein two recombination processes were observed with rates almost identical with those observed in the stopped-flow experiments (k+1 = 3.3 X 10(3)M-1-S-1 and k+2 = 6.0 X 10(2)M-1-S-1). These findings provide evidence of two reduced forms of the protein. The reduction of [methionine sulphoxide]cytochrome c by Cr2+ at neutral pH in stopped-flow experiments showed the presence of a single second-order reduction process (k = 7.2 X 10(3)M-1-S-1, activation energy = 44kJ/mol) and one first-order process. This protein was compared with some other chemically modified cytochromes."}
{"id": "PMID:188411", "title": "A comparison of bone matrix and tendon with particular reference to glycoprotein content.", "content": "Bone matrix and tendon are compared in terms of their carbohydrate and non-collagenous protein composition. The collagen content of both tissues was similar (90-91%), but bone matrix had at least three times as much sialic acid (0.28%) as tendon (0.08%). Smaller differences were found in the analysis of hexoses and hexosamines. After digestion with bacterial collagenase, about 9% of the total protein from both tissues was non-diffusible on dialysis, and this contained only 0.15% (bone) and 0.7% (tendon) of the original hydroxyproline; recovery of sialic acid was 86-87%. The collagenase-resistant soluble material amounted to about 9% (bone matrix) and 5% (tendon); the insoluble residues were 1 and 4% respectively. There were clear differences in the carbohydrate contents of the digests, but the amino acid compositions were similar. When the soluble digests were chromatographed on DEAE-cellulose, the elution profiles indicated the presence in each tissue of a variety of glycoproteins and a proteoglycan fraction, and showed clearly that an acidic glycoprotein corresponding to bone sialoprotein was not present in tendon.", "contents": "A comparison of bone matrix and tendon with particular reference to glycoprotein content. Bone matrix and tendon are compared in terms of their carbohydrate and non-collagenous protein composition. The collagen content of both tissues was similar (90-91%), but bone matrix had at least three times as much sialic acid (0.28%) as tendon (0.08%). Smaller differences were found in the analysis of hexoses and hexosamines. After digestion with bacterial collagenase, about 9% of the total protein from both tissues was non-diffusible on dialysis, and this contained only 0.15% (bone) and 0.7% (tendon) of the original hydroxyproline; recovery of sialic acid was 86-87%. The collagenase-resistant soluble material amounted to about 9% (bone matrix) and 5% (tendon); the insoluble residues were 1 and 4% respectively. There were clear differences in the carbohydrate contents of the digests, but the amino acid compositions were similar. When the soluble digests were chromatographed on DEAE-cellulose, the elution profiles indicated the presence in each tissue of a variety of glycoproteins and a proteoglycan fraction, and showed clearly that an acidic glycoprotein corresponding to bone sialoprotein was not present in tendon."}
{"id": "PMID:188412", "title": "The amino acid sequences of the cytochromes c-555 from two green sulphur bacteria of the genus Chlorobium.", "content": "Amino acid seauences are proposed for the cytochromes c-555 from Chlorobium thiosulphatophilum and from the Chlorobium limicola component of \"Chloropseudomonas ethylica 2K\". Each is a sincle polypeptide chain, the former of 86, the latter of 99 residues, and, when aligned so as to give the best match, 47 residues are common to the two sequences. The sequences show some resemblance to those of cytochromes c5 and f. The bacteriochlorophyll a-proteins were also isolated and purified, and their amino acid compositions compared (see the Appendix). There are significant differences in the compositions, but not as great as those found for the cytochromes c-555. The significance of these observations for the taxonomy of the Chlorobiaceae and for the further development of the comparative biochemistry of cytochrome c is discussed. Detailed evidence for the sequences of the cytochromes c-555 has been deposited as Supplementary Publication SUP 50073 (36 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1976) 153, 5.", "contents": "The amino acid sequences of the cytochromes c-555 from two green sulphur bacteria of the genus Chlorobium. Amino acid seauences are proposed for the cytochromes c-555 from Chlorobium thiosulphatophilum and from the Chlorobium limicola component of \"Chloropseudomonas ethylica 2K\". Each is a sincle polypeptide chain, the former of 86, the latter of 99 residues, and, when aligned so as to give the best match, 47 residues are common to the two sequences. The sequences show some resemblance to those of cytochromes c5 and f. The bacteriochlorophyll a-proteins were also isolated and purified, and their amino acid compositions compared (see the Appendix). There are significant differences in the compositions, but not as great as those found for the cytochromes c-555. The significance of these observations for the taxonomy of the Chlorobiaceae and for the further development of the comparative biochemistry of cytochrome c is discussed. Detailed evidence for the sequences of the cytochromes c-555 has been deposited as Supplementary Publication SUP 50073 (36 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1976) 153, 5."}
{"id": "PMID:188413", "title": "Low-temperature studies on mixed-valence cytochrome oxidase by using magnetic circular dichroism.", "content": "The spin states of the haem components of mixed-valence cytochrome oxidase were studied at room temperature and at temperature down to 20K by using magnetic circular dichroism. The room-temperature studies show the presence of a low-spin ferrous haem together with a low-spin ferric haem, which we attribute to heams a3 and a respectively. At temperatures below 100K it appears that the CO of the mixed-valence CO complex may be irreversibly photolysed, and that in this case haems a and a3 assume their high-spin states. Thus in this enzyme haem-haem interactions appear possible at temperatures below 100K.", "contents": "Low-temperature studies on mixed-valence cytochrome oxidase by using magnetic circular dichroism. The spin states of the haem components of mixed-valence cytochrome oxidase were studied at room temperature and at temperature down to 20K by using magnetic circular dichroism. The room-temperature studies show the presence of a low-spin ferrous haem together with a low-spin ferric haem, which we attribute to heams a3 and a respectively. At temperatures below 100K it appears that the CO of the mixed-valence CO complex may be irreversibly photolysed, and that in this case haems a and a3 assume their high-spin states. Thus in this enzyme haem-haem interactions appear possible at temperatures below 100K."}
{"id": "PMID:188414", "title": "Role of histone kinases as mediators of corticotropin-induced steroidogenesis.", "content": "In an attempt to determine the role of protein (histone) kinases as mediators of corticotropin-induced corticosterone formation, the ability of homogenates, prepared from adrenals treated with various doses of corticotropin to catalyse the phosphorylation of calf thymus histones was measured. Although corticotropin promoted an increase in histone kinase activity, much more of the hormone was required to induce this response than to stimulate steroidogenesis maximally. In addition, a derivative, nitrophenylsulphenyl-corticotropin, which inhibits the stimulatory effect of corticotropin on cyclic AMP accumulation, stimulated corticosterone synthesis without altering histone kinase activity. Very high doses of nitrophenylsulphenyl-corticotropin were capable of stimulating histone kinase activity. In contrast, when dibutyryl cyclic AMP was used to stimulate steroidogenesis under the same conditions, any dose of the nucleotide which increased adrenal corticosteroid content also increased histone kinase activity. Assuming that histones serve as useful substrates for measurement of total adrenal protein kinase activity, the role of protein kinases as mediators of steroidogenesis is not supported by these studies.", "contents": "Role of histone kinases as mediators of corticotropin-induced steroidogenesis. In an attempt to determine the role of protein (histone) kinases as mediators of corticotropin-induced corticosterone formation, the ability of homogenates, prepared from adrenals treated with various doses of corticotropin to catalyse the phosphorylation of calf thymus histones was measured. Although corticotropin promoted an increase in histone kinase activity, much more of the hormone was required to induce this response than to stimulate steroidogenesis maximally. In addition, a derivative, nitrophenylsulphenyl-corticotropin, which inhibits the stimulatory effect of corticotropin on cyclic AMP accumulation, stimulated corticosterone synthesis without altering histone kinase activity. Very high doses of nitrophenylsulphenyl-corticotropin were capable of stimulating histone kinase activity. In contrast, when dibutyryl cyclic AMP was used to stimulate steroidogenesis under the same conditions, any dose of the nucleotide which increased adrenal corticosteroid content also increased histone kinase activity. Assuming that histones serve as useful substrates for measurement of total adrenal protein kinase activity, the role of protein kinases as mediators of steroidogenesis is not supported by these studies."}
{"id": "PMID:188415", "title": "Studies on the control of 4-aminobutyrate metabolism in 'synaptosomal' and free rat brain mitochondria.", "content": "1. The specific activities of 4-aminobutyrate aminotransferase (EC 2.6.1.19) and succinate semialdehyde dehydrogenase (EC 1.2.1.16) were significantly higher in brain mitochondria of non-synaptic origin (fraction M) than those derived from the lysis of synaptosomes (fraction SM2). 2. The metabolisms of 4-aminobutyrate in both 'free' (non-synaptic, fraction M) and 'synaptic' (fraction SM2) rat brain mitochondria was studied under various conditions. 3. It is proposed that 4-aminobutyrate enters both types of brain mitochondria by a non-carrier-mediated process. 4. The rate of 4-aminobutyrate metabolism was in all cases higher in the 'free' (fraction M) brain mitochondria than in the synaptic (fraction SM2) mitochondria, paralleling the differences in the specific activities of the 4-aminobutyrate-shunt enzymes. 5. The intramitochondrial concentration of 2-oxoglutarate appears to be an important controlling parameter in the rate of 4-aminobutyrate metabolism, since, although 2-oxoglutarate is required, high concentrations (2.5 mM) of extramitochondrial 2-oxoglutarate inhibit the formation of aspartate via the glutamate-oxaloacetate transaminase. 6. The redox state of the intramitochondrial NAD pool is also important in the control of 4-aminobutyrate metabolism; NADH exhibits competitive inhibition of 4-aminobutyrate metabolism by both mitochondrial populations with an apparent Ki of 102 muM. 7. Increased potassium concentrations stimulate 4-aminobutyrate metabolsim in the synaptic mitochondria but not in 'free' brain mitochondria. This is discussed with respect to the putative transmitter role of 4-aminobutyrate.", "contents": "Studies on the control of 4-aminobutyrate metabolism in 'synaptosomal' and free rat brain mitochondria. 1. The specific activities of 4-aminobutyrate aminotransferase (EC 2.6.1.19) and succinate semialdehyde dehydrogenase (EC 1.2.1.16) were significantly higher in brain mitochondria of non-synaptic origin (fraction M) than those derived from the lysis of synaptosomes (fraction SM2). 2. The metabolisms of 4-aminobutyrate in both 'free' (non-synaptic, fraction M) and 'synaptic' (fraction SM2) rat brain mitochondria was studied under various conditions. 3. It is proposed that 4-aminobutyrate enters both types of brain mitochondria by a non-carrier-mediated process. 4. The rate of 4-aminobutyrate metabolism was in all cases higher in the 'free' (fraction M) brain mitochondria than in the synaptic (fraction SM2) mitochondria, paralleling the differences in the specific activities of the 4-aminobutyrate-shunt enzymes. 5. The intramitochondrial concentration of 2-oxoglutarate appears to be an important controlling parameter in the rate of 4-aminobutyrate metabolism, since, although 2-oxoglutarate is required, high concentrations (2.5 mM) of extramitochondrial 2-oxoglutarate inhibit the formation of aspartate via the glutamate-oxaloacetate transaminase. 6. The redox state of the intramitochondrial NAD pool is also important in the control of 4-aminobutyrate metabolism; NADH exhibits competitive inhibition of 4-aminobutyrate metabolism by both mitochondrial populations with an apparent Ki of 102 muM. 7. Increased potassium concentrations stimulate 4-aminobutyrate metabolsim in the synaptic mitochondria but not in 'free' brain mitochondria. This is discussed with respect to the putative transmitter role of 4-aminobutyrate."}
{"id": "PMID:188416", "title": "Changes in the activities of the enzymes of urea synthesis caused by dexamethasone and dibutyryladenosine 3':5'-cyclic monophosphate in foetal rat liver maintained in organ culture.", "content": "Liver explants from 19-day foetal rats were maintained in organ culture, in a defined medium, for up to 48h. Both 6-N,2'-O-dibutyryl cyclic AMP, in the presence of theophylline, and dexamethasone caused an increase in the activities of carbamoyl phosphate synthase, argininosuccinate synthetase, argininosuccinate lyase and arginase. These increases could be abolished by simultaneously incubating the explants with cycloheximide. No change in the activity of ornithine transcarbamoylase was found with either hormone. Previous work has shown that injection of corticosteroids into 19.5-day foetal rats in utero did not cause an increase in the arginine synthetase system. Present results suggest that this lack of effect is not due to any incompetence of the foetal rat liver at this stage to respond to this agent. The observations on ornithine transcarbamoylase activity suggest that this enzyme is induced in the liver of the perinatal rat by neither corticosteroids nor hormones acting via cyclic AMP, and it may be that all the enzymes of the urea cycle are induced physiologically by an agent or agents as yet unidentified.", "contents": "Changes in the activities of the enzymes of urea synthesis caused by dexamethasone and dibutyryladenosine 3':5'-cyclic monophosphate in foetal rat liver maintained in organ culture. Liver explants from 19-day foetal rats were maintained in organ culture, in a defined medium, for up to 48h. Both 6-N,2'-O-dibutyryl cyclic AMP, in the presence of theophylline, and dexamethasone caused an increase in the activities of carbamoyl phosphate synthase, argininosuccinate synthetase, argininosuccinate lyase and arginase. These increases could be abolished by simultaneously incubating the explants with cycloheximide. No change in the activity of ornithine transcarbamoylase was found with either hormone. Previous work has shown that injection of corticosteroids into 19.5-day foetal rats in utero did not cause an increase in the arginine synthetase system. Present results suggest that this lack of effect is not due to any incompetence of the foetal rat liver at this stage to respond to this agent. The observations on ornithine transcarbamoylase activity suggest that this enzyme is induced in the liver of the perinatal rat by neither corticosteroids nor hormones acting via cyclic AMP, and it may be that all the enzymes of the urea cycle are induced physiologically by an agent or agents as yet unidentified."}
{"id": "PMID:188417", "title": "Studies on the phosphorylation of the inhibitory subunit of troponin during modification of contraction in perfused rat heart.", "content": "1. Rat hearts were perfused with 32Pi, and contractile force was increased by positive inotropic agents (agents that increase contractility). The inhibitory subunit of troponin (troponin I) was then isolated by affinity chromatography in 8M-urea, and its 32P content measured. Incorporation of phosphate into the subunit was calculated on the basis of the [gamma-32P]ATP specific radioactivity in the hearts. 2. When hearts were perfused with 30 nM-DL-isoprenaline (N-isopropylnoradrenaline), there was an increase in contractile force over 30s which was paralleled by an increase in troponin I phosphorylation. When hearts were perfused for 25s with increasing concentrations of isoprenaline from 1 NM to 0.6 muM, there was again a parallel increase in contractile force and troponin I phosphorylation. The maximum phosphorylation observed was 1.5 mol of phosphate/mol of troponin I, which was reached after 25s with 0.1 muM-isoprenaline. 3. Hearts were stimulated with a 15s pulse perfusion of 30nM-DL-isoprenaline. There was an increase in contractile force which was followed by a return to the control value within 50s. Troponin I phosphorylation increased to a plateau value which was reached within 30s, and remained constant for 60s after the isoprenaline pulse. Phosphorylase a and 3':5'-cyclic AMP concentration showed changes similar to that of the contractile force. There was no change in 3':5'-cyclic GMP concentration. 4. When hearts stimulated with a 15S pulse of isoprenaline were subsequently perfused with 0.6 muM-acetylcholine, the changes in contractile force, phosphorylase a and 3':5'-cyclic AMP were very similar to those seen with the 15s pulse of isoprenaline alone. Troponin I phosphorylation increased to a maximum 30s after the end of the isoprenaline pulse, but then rapidly decreased during the subsequent 30s. This decrease was preceded by a 60% increase in the concentration of 3':5'-cyclic GMP. 5. Hearts were perfused with 0.2 muM-glucagon for periods up to 60s. Contractile force showed little change for the first 30s, but then increased rapidly. This was paralleled by changes in 3':5'-cyclic AMP concentration. Troponin I phosphorylation increased slowly, but the increase in contractile force had reached a maximum before significant phosphorylation had occurred. 6. It is concluded that under certain conditions, e.g. immediately after beta-adrenergic stimulation, there is a good correlation between contractile force and troponin I phosphorylation. However, under other conditions, e.g. when contractile force is decreasing after removal of beta-adrenergic stimulation or in the presence of glucagon, contractile force and troponin I phosphorylation are not well correlated. These results suggest that mechanisms for modifying cardiac contractility, other than troponin I phosphorylation, must be present in rat heart.", "contents": "Studies on the phosphorylation of the inhibitory subunit of troponin during modification of contraction in perfused rat heart. 1. Rat hearts were perfused with 32Pi, and contractile force was increased by positive inotropic agents (agents that increase contractility). The inhibitory subunit of troponin (troponin I) was then isolated by affinity chromatography in 8M-urea, and its 32P content measured. Incorporation of phosphate into the subunit was calculated on the basis of the [gamma-32P]ATP specific radioactivity in the hearts. 2. When hearts were perfused with 30 nM-DL-isoprenaline (N-isopropylnoradrenaline), there was an increase in contractile force over 30s which was paralleled by an increase in troponin I phosphorylation. When hearts were perfused for 25s with increasing concentrations of isoprenaline from 1 NM to 0.6 muM, there was again a parallel increase in contractile force and troponin I phosphorylation. The maximum phosphorylation observed was 1.5 mol of phosphate/mol of troponin I, which was reached after 25s with 0.1 muM-isoprenaline. 3. Hearts were stimulated with a 15s pulse perfusion of 30nM-DL-isoprenaline. There was an increase in contractile force which was followed by a return to the control value within 50s. Troponin I phosphorylation increased to a plateau value which was reached within 30s, and remained constant for 60s after the isoprenaline pulse. Phosphorylase a and 3':5'-cyclic AMP concentration showed changes similar to that of the contractile force. There was no change in 3':5'-cyclic GMP concentration. 4. When hearts stimulated with a 15S pulse of isoprenaline were subsequently perfused with 0.6 muM-acetylcholine, the changes in contractile force, phosphorylase a and 3':5'-cyclic AMP were very similar to those seen with the 15s pulse of isoprenaline alone. Troponin I phosphorylation increased to a maximum 30s after the end of the isoprenaline pulse, but then rapidly decreased during the subsequent 30s. This decrease was preceded by a 60% increase in the concentration of 3':5'-cyclic GMP. 5. Hearts were perfused with 0.2 muM-glucagon for periods up to 60s. Contractile force showed little change for the first 30s, but then increased rapidly. This was paralleled by changes in 3':5'-cyclic AMP concentration. Troponin I phosphorylation increased slowly, but the increase in contractile force had reached a maximum before significant phosphorylation had occurred. 6. It is concluded that under certain conditions, e.g. immediately after beta-adrenergic stimulation, there is a good correlation between contractile force and troponin I phosphorylation. However, under other conditions, e.g. when contractile force is decreasing after removal of beta-adrenergic stimulation or in the presence of glucagon, contractile force and troponin I phosphorylation are not well correlated. These results suggest that mechanisms for modifying cardiac contractility, other than troponin I phosphorylation, must be present in rat heart."}
{"id": "PMID:188428", "title": "[Studies on the Pharmacology of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolon valerate) (author's transl)].", "content": "The topical and systemic anti-inflammatory action of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolone valerate, Nerisona) was studied in the rat in comparison with fluocortolone, diflucortolone and some other corticoids. In addition the effect of the compounds studied on the following parameters of corticoid activity was examined in the rat: body weight and weights of thymus, spleen and adrenals; blood sugar concentration and liver glycogen content; diuresis and Na+ and K+ elimination with the urine; the binding of diflucortolone and some diflucortolone-21-esters to the cytoplasmic corticoid receptor of the rat's thymus was also determined. In all tests diflucortolone was shown to be a corticoid with very potent topical and systemic action. Diflucortolone valerate showed the same potent anti-inflammatory action on topical application as the unesterified compound. After subcutaneous administration, however, the systemic corticoid action of the valerate was considerably inferior to that of diflucortolone on account of the kinetics of the more lipid soluble ester.", "contents": "[Studies on the Pharmacology of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolon valerate) (author's transl)]. The topical and systemic anti-inflammatory action of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolone valerate, Nerisona) was studied in the rat in comparison with fluocortolone, diflucortolone and some other corticoids. In addition the effect of the compounds studied on the following parameters of corticoid activity was examined in the rat: body weight and weights of thymus, spleen and adrenals; blood sugar concentration and liver glycogen content; diuresis and Na+ and K+ elimination with the urine; the binding of diflucortolone and some diflucortolone-21-esters to the cytoplasmic corticoid receptor of the rat's thymus was also determined. In all tests diflucortolone was shown to be a corticoid with very potent topical and systemic action. Diflucortolone valerate showed the same potent anti-inflammatory action on topical application as the unesterified compound. After subcutaneous administration, however, the systemic corticoid action of the valerate was considerably inferior to that of diflucortolone on account of the kinetics of the more lipid soluble ester."}
{"id": "PMID:188429", "title": "[Systemic effect of diflucortolone valerate after dermal application (author's transl)].", "content": "The systemic effect of 6alpha,9-difluor-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolone valerate, Nerisona) 0.1% as an ointment and fatty ointment was investigated in two studies. The parameters used were the plasma 11-OHCS values and the urinary 17-OHCS and 17-KS values, respectively. Suppression of the plasma cortisol values was observed after topical application of both diflucortolone valerate and betamethasone-17-valerate to healthy subjects under extreme conditions of whole-body occlusion. However, it was still possible to stimulate the adrenal cortex with ACTH. No reduction of the 17-OHCS of 17-KS values in the 24-h urine was observed during open, large-surface treatment of patients with skin diseases.", "contents": "[Systemic effect of diflucortolone valerate after dermal application (author's transl)]. The systemic effect of 6alpha,9-difluor-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolone valerate, Nerisona) 0.1% as an ointment and fatty ointment was investigated in two studies. The parameters used were the plasma 11-OHCS values and the urinary 17-OHCS and 17-KS values, respectively. Suppression of the plasma cortisol values was observed after topical application of both diflucortolone valerate and betamethasone-17-valerate to healthy subjects under extreme conditions of whole-body occlusion. However, it was still possible to stimulate the adrenal cortex with ACTH. No reduction of the 17-OHCS of 17-KS values in the 24-h urine was observed during open, large-surface treatment of patients with skin diseases."}
{"id": "PMID:188430", "title": "Control of the interaction of cholesterol ester-rich lipoproteins with arterial receptors.", "content": "Incorporation of 125I-labeled cholesterol ester rich lipoproteins from cholesterol fed rabbits into normal rabbit aorta in vitro was inhibited by heparin, lecithin, and collagenase and by succinylation of the lipoprotein. Aortic uptake of lipoprotein was increased by neuraminidase, proteases, lipase, and beta-glucuronidase. These results suggest that it may be possible to control atherogenesis by controlling the interaction of atherogenic lipoproteins with their arterial receptor.", "contents": "Control of the interaction of cholesterol ester-rich lipoproteins with arterial receptors. Incorporation of 125I-labeled cholesterol ester rich lipoproteins from cholesterol fed rabbits into normal rabbit aorta in vitro was inhibited by heparin, lecithin, and collagenase and by succinylation of the lipoprotein. Aortic uptake of lipoprotein was increased by neuraminidase, proteases, lipase, and beta-glucuronidase. These results suggest that it may be possible to control atherogenesis by controlling the interaction of atherogenic lipoproteins with their arterial receptor."}
{"id": "PMID:188431", "title": "Binding to plasma lipoproteins of chlorophenoxyisobutyric, tibric and nicotinic acids and their esters: its significance for the mechanism of lipid lowering by clofibrate and related drugs.", "content": "The binding of chlorophenoxyisobutyric (CPIB), tibric (TA) and nicotinic (NA) acids and CPIB ethyl ester (Clofibrate), TA and NA isopropyl esters (TAPE and NAPE) to human lipoproteins of low density of different classes (LDL2, LDL1 and VLDL) and high density (HDL) were studied by equilibrium dialysis and Sephadex gel filtration. Clofibrate and TAPE bound strongly to lipoproteins, but their acids, CPIB and TA and also NA and NAPE, did not bind. In the same experimental conditions, Clofibrate and TAPE bound only weakly to human serum albumin (HSA) and CPIB bound to HSA with a Ka of 3.3 X 10(5) M(-1) for 1 site of high affinity. The Clofibrate and TAPE bound to lipoproteins did not dissociate either during dialysis or during filtration on Sephadex G 25. The binding percentage remained constant for all drug concentrations studied, and the molar ratio of bound drug rose linearly with increasing concentrations. This suggests that the interaction may be irreversible, and there is some evidence that binding may induce irreversible changes in the lipoprotein molecules. These results, and those already found in experiments made with three other drugs related to Clofibrate, lead to the proposal that in their interaction with lipoproteins, the phenyl groups are necessary and the esterification is contributory. The possible role of this interaction in the lipid-lowering effect of the drugs is discussed with special reference to their possible implication in lipoprotein synthesis within the intestinal and hepatic cells.", "contents": "Binding to plasma lipoproteins of chlorophenoxyisobutyric, tibric and nicotinic acids and their esters: its significance for the mechanism of lipid lowering by clofibrate and related drugs. The binding of chlorophenoxyisobutyric (CPIB), tibric (TA) and nicotinic (NA) acids and CPIB ethyl ester (Clofibrate), TA and NA isopropyl esters (TAPE and NAPE) to human lipoproteins of low density of different classes (LDL2, LDL1 and VLDL) and high density (HDL) were studied by equilibrium dialysis and Sephadex gel filtration. Clofibrate and TAPE bound strongly to lipoproteins, but their acids, CPIB and TA and also NA and NAPE, did not bind. In the same experimental conditions, Clofibrate and TAPE bound only weakly to human serum albumin (HSA) and CPIB bound to HSA with a Ka of 3.3 X 10(5) M(-1) for 1 site of high affinity. The Clofibrate and TAPE bound to lipoproteins did not dissociate either during dialysis or during filtration on Sephadex G 25. The binding percentage remained constant for all drug concentrations studied, and the molar ratio of bound drug rose linearly with increasing concentrations. This suggests that the interaction may be irreversible, and there is some evidence that binding may induce irreversible changes in the lipoprotein molecules. These results, and those already found in experiments made with three other drugs related to Clofibrate, lead to the proposal that in their interaction with lipoproteins, the phenyl groups are necessary and the esterification is contributory. The possible role of this interaction in the lipid-lowering effect of the drugs is discussed with special reference to their possible implication in lipoprotein synthesis within the intestinal and hepatic cells."}
{"id": "PMID:188434", "title": "Lipoprotein levels in apparently healthy men and women in the west of Scotland.", "content": "Lipoprotein typing was undertaken in apparently healthy women (419) and men (103) in whom measurements of fasting total cholesterol, triglycerides, and cholesterol content of the major lipoprotein fractions were made. In the female group (30 to 59 years) there was a significant rise in total cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides with age. Using total cholesterol and triglyceride levels for classification, type II hyperlipoproteinaemia was present in 1 per cent and type IV in 6-7 per cent. When LDL cholesterol levels were also considered, type II occurred in 9-8 per cent ( 8-4% type IIA and 1-4% type IIB). In the male group ( 40 to 59 years) there was no increase in cholesterol or triglyceride levels with age: II per cent had type IV hyperlipoproteinaemia and none had a type II abnormality. When LDL cholesterol levels were also considered, type II occurred in 3 per cent ( 2% type IIA and 1% IIB). The apparent increase in LDL cholesterol frequency of type IIA abnormality in women could be merely the consequence of arbitrary selection of upper limits of normality for LDL cholesterol, but may signify improved detection of a high risk group.", "contents": "Lipoprotein levels in apparently healthy men and women in the west of Scotland. Lipoprotein typing was undertaken in apparently healthy women (419) and men (103) in whom measurements of fasting total cholesterol, triglycerides, and cholesterol content of the major lipoprotein fractions were made. In the female group (30 to 59 years) there was a significant rise in total cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides with age. Using total cholesterol and triglyceride levels for classification, type II hyperlipoproteinaemia was present in 1 per cent and type IV in 6-7 per cent. When LDL cholesterol levels were also considered, type II occurred in 9-8 per cent ( 8-4% type IIA and 1-4% type IIB). In the male group ( 40 to 59 years) there was no increase in cholesterol or triglyceride levels with age: II per cent had type IV hyperlipoproteinaemia and none had a type II abnormality. When LDL cholesterol levels were also considered, type II occurred in 3 per cent ( 2% type IIA and 1% IIB). The apparent increase in LDL cholesterol frequency of type IIA abnormality in women could be merely the consequence of arbitrary selection of upper limits of normality for LDL cholesterol, but may signify improved detection of a high risk group."}
{"id": "PMID:188435", "title": "Effect of oestrogens on postexercise electrocardiogram.", "content": "The effect of three oestrogens (including an oestrogen-progestogen combination) on the postexercise electrocardiogram was studied in 33 men and 18 women who earlier had shown ST segment abnormalities after exercise. When pretreatment exercise tests were compared with tests after two weeks of treatment, the postexercise ST segments which were abnormal before treatment became even more abnormal in 18 (90%) of 20 subjects treated with conjugated oestrogens 10 mg daily, in 16 (89%) of 18 subjects treated with stilboestrol 5 mg daily, and in 12 (92%) of 13 subjects treated with norethynodrel (9-85 mg) and mestranol (0-15 mg)1 daily. The ST segment abnormalities reverted to pretreatment appearance within 6 weeks of stopping oestrogens. When 10 subjects with normal near-maximal exercise tests were treated for 2 weeks with conjugated oestrogens 10 mg daily, the tests remained unchanged in 9. The hypothesis favoured to explain these findings is that of an oestrogen-induced increase in coronary artery smooth muscle tone. An increase in arterial tone would also account for the increased incidence of myocardial (and cerebral) infarction that has been reported among individuals treated with oestrogen, either alone or in combination with progestogen.", "contents": "Effect of oestrogens on postexercise electrocardiogram. The effect of three oestrogens (including an oestrogen-progestogen combination) on the postexercise electrocardiogram was studied in 33 men and 18 women who earlier had shown ST segment abnormalities after exercise. When pretreatment exercise tests were compared with tests after two weeks of treatment, the postexercise ST segments which were abnormal before treatment became even more abnormal in 18 (90%) of 20 subjects treated with conjugated oestrogens 10 mg daily, in 16 (89%) of 18 subjects treated with stilboestrol 5 mg daily, and in 12 (92%) of 13 subjects treated with norethynodrel (9-85 mg) and mestranol (0-15 mg)1 daily. The ST segment abnormalities reverted to pretreatment appearance within 6 weeks of stopping oestrogens. When 10 subjects with normal near-maximal exercise tests were treated for 2 weeks with conjugated oestrogens 10 mg daily, the tests remained unchanged in 9. The hypothesis favoured to explain these findings is that of an oestrogen-induced increase in coronary artery smooth muscle tone. An increase in arterial tone would also account for the increased incidence of myocardial (and cerebral) infarction that has been reported among individuals treated with oestrogen, either alone or in combination with progestogen."}
{"id": "PMID:188432", "title": "Comparison of the serum low density lipoprotein and of its apoprotein in the pig, rhesus monkey and baboon with that in man.", "content": "The principal form of the serum low density lipoprotein (LDL) in man, baboon, rhesus monkey and pig was isolated by preparative ultracentrifugation in the density interval 1.024-1.045 g/ml. The physicochemical characteristics of pig LDL most closely resembled those of man; thus, electrophoretic studies suggested that both baboon and rhesus LDL have a greater surface charge than that of their human counterpart, and electron-microscopic investigations showed baboon LDL (245 A) to be larger and rhesus LDL (205 A) smaller than those of man (217 A) and pig (228 A). In contrast, the immunological relationship between LDL from the two Old World monkeys and that of man was much closer (80-85% cross-reactivity by micro-immunoprecipitation) than that between pig and man (35% cross-reactivity). The principal difference between pig and human LDL appeared to reside in their protein and carbohydrate moieties. There was a marked resemblance between the protein moieties (apo-LDL) of LDL from the four species. The principal component of each animal apo-LDL was separated by gel-filtration chromatography and amounted to greater than 95% of the total protein; it exhibited a high molecular weight (greater than 250,000) upon SDS-polyacrylamide-gel electrophoresis and was indistinguishable from human apolipoprotein B in amino acid composition. Differences both between the apo-LDL and between the apo-B preparations from the four species, however, were detectable by immunological procedures. Such studies revealed inter-species relationships which were essentially the same as those observed between the respective native LDL preparations. The soluble apolipoproteins, present as minor components (less than 5%) of each apo-LDL, were compared by their electrophoretic mobility in polyacrylamide gel; the pattern seen in baboon and rhesus apo-LDL appeared to be most closely akin to that typical of their human counterpart. It is apparent that many characteristics typical of human serum LDL are found in those of the pig, rhesus monkey and baboon. Moreover, in view of the striking relationship existing between the immunological properties and apo-protein components of the LDL of the two Old World monkeys and that of man, these subhuman primates appear to be highly suitable as animal models for experimental atherosclerosis.", "contents": "Comparison of the serum low density lipoprotein and of its apoprotein in the pig, rhesus monkey and baboon with that in man. The principal form of the serum low density lipoprotein (LDL) in man, baboon, rhesus monkey and pig was isolated by preparative ultracentrifugation in the density interval 1.024-1.045 g/ml. The physicochemical characteristics of pig LDL most closely resembled those of man; thus, electrophoretic studies suggested that both baboon and rhesus LDL have a greater surface charge than that of their human counterpart, and electron-microscopic investigations showed baboon LDL (245 A) to be larger and rhesus LDL (205 A) smaller than those of man (217 A) and pig (228 A). In contrast, the immunological relationship between LDL from the two Old World monkeys and that of man was much closer (80-85% cross-reactivity by micro-immunoprecipitation) than that between pig and man (35% cross-reactivity). The principal difference between pig and human LDL appeared to reside in their protein and carbohydrate moieties. There was a marked resemblance between the protein moieties (apo-LDL) of LDL from the four species. The principal component of each animal apo-LDL was separated by gel-filtration chromatography and amounted to greater than 95% of the total protein; it exhibited a high molecular weight (greater than 250,000) upon SDS-polyacrylamide-gel electrophoresis and was indistinguishable from human apolipoprotein B in amino acid composition. Differences both between the apo-LDL and between the apo-B preparations from the four species, however, were detectable by immunological procedures. Such studies revealed inter-species relationships which were essentially the same as those observed between the respective native LDL preparations. The soluble apolipoproteins, present as minor components (less than 5%) of each apo-LDL, were compared by their electrophoretic mobility in polyacrylamide gel; the pattern seen in baboon and rhesus apo-LDL appeared to be most closely akin to that typical of their human counterpart. It is apparent that many characteristics typical of human serum LDL are found in those of the pig, rhesus monkey and baboon. Moreover, in view of the striking relationship existing between the immunological properties and apo-protein components of the LDL of the two Old World monkeys and that of man, these subhuman primates appear to be highly suitable as animal models for experimental atherosclerosis."}
{"id": "PMID:188433", "title": "[Hypocalcemic vitamin D-dependent renal rickets].", "content": "Two siblings, female 10 years old, and male 15 years old, with the diagnosis of vitamin D-dependent rickets were studied. Another sibling, also with the same diagnosis, died of bronchopnemonia at about 7 months of age. Both patients developed rachitic manifestations since the first year of life, which persisted despite the administration of massive doses of vitamin D intermitently. Severe hypocalcemia, moderate hypophosphatemia and elevated serum alkaline phosphatase were the most characteristic biochemical findings. Both patients showed diminished renal tubular reabsorption of amino acids and phosphates. These alterations were reversible during I.V. calcium gluconate administration. The clinical biochemical and X-ray manifestations disappeared completely after one year of treatment with dihydrotaquisterol. Vitamin D-dependent rickets is an autosomal recessive disease, characterized by a hydroxylation defect of 25 hydroxycholecalciferol at the carbon 1 level, due to abscence of 25 hydroxy-D1-hydroxylase. Thus 1-25 Dihydroxycholecalciferol, the active form of vitamin D3 is not formed, resulting in depression of intestinal calcium absorption and reabsorption from the bones.", "contents": "[Hypocalcemic vitamin D-dependent renal rickets]. Two siblings, female 10 years old, and male 15 years old, with the diagnosis of vitamin D-dependent rickets were studied. Another sibling, also with the same diagnosis, died of bronchopnemonia at about 7 months of age. Both patients developed rachitic manifestations since the first year of life, which persisted despite the administration of massive doses of vitamin D intermitently. Severe hypocalcemia, moderate hypophosphatemia and elevated serum alkaline phosphatase were the most characteristic biochemical findings. Both patients showed diminished renal tubular reabsorption of amino acids and phosphates. These alterations were reversible during I.V. calcium gluconate administration. The clinical biochemical and X-ray manifestations disappeared completely after one year of treatment with dihydrotaquisterol. Vitamin D-dependent rickets is an autosomal recessive disease, characterized by a hydroxylation defect of 25 hydroxycholecalciferol at the carbon 1 level, due to abscence of 25 hydroxy-D1-hydroxylase. Thus 1-25 Dihydroxycholecalciferol, the active form of vitamin D3 is not formed, resulting in depression of intestinal calcium absorption and reabsorption from the bones."}
{"id": "PMID:188437", "title": "Epstein-Barr-virus-specific IgA and IgG serum antibodies in nasopharyngeal carcinoma.", "content": "The sera of 73 patients with nasopharyngeal carcinoma (NPC), 28 patients with other carcinomas (OC) and 89 healthy subjects (HS) were tested for IgG and IgA antibodies to Epstein-Barr virus (EBV) viral capsid antigen (VCA). The majority of the NPC sera had IgG titres of 160 or above, whereas the majority of the other sera had titres below 160. For IgA reactivity to EBV-VCA, 68 of 73 (93-2%) NPC sera had titres of greater than or equal to 10. In contrast, only 6 of 28 (21-4%) OC sera and none of the HS sera had such titres. The mean serum concentrations of IgG, IgA, IgM and C3' were also determined in 55 NPC and 20 OC patients and 18 HS. They were all significantly higher in the NPC sera than in the HS. Although the concentrations of IgG and C3' were not significantly different in the two carcinoma groups, the concentrations of IgA and IgM were significantly higher in the NPC group than in OC. These findings appear to reflect the intensity of EBV-specific antigenic stimulation in NPC, and the EBV-specific serum IgA reactivity may be a sueful aid to the diagnosis of NPC, especially in cases with an occult primary tumour. It may be also of value as a screening test in people at high risk.", "contents": "Epstein-Barr-virus-specific IgA and IgG serum antibodies in nasopharyngeal carcinoma. The sera of 73 patients with nasopharyngeal carcinoma (NPC), 28 patients with other carcinomas (OC) and 89 healthy subjects (HS) were tested for IgG and IgA antibodies to Epstein-Barr virus (EBV) viral capsid antigen (VCA). The majority of the NPC sera had IgG titres of 160 or above, whereas the majority of the other sera had titres below 160. For IgA reactivity to EBV-VCA, 68 of 73 (93-2%) NPC sera had titres of greater than or equal to 10. In contrast, only 6 of 28 (21-4%) OC sera and none of the HS sera had such titres. The mean serum concentrations of IgG, IgA, IgM and C3' were also determined in 55 NPC and 20 OC patients and 18 HS. They were all significantly higher in the NPC sera than in the HS. Although the concentrations of IgG and C3' were not significantly different in the two carcinoma groups, the concentrations of IgA and IgM were significantly higher in the NPC group than in OC. These findings appear to reflect the intensity of EBV-specific antigenic stimulation in NPC, and the EBV-specific serum IgA reactivity may be a sueful aid to the diagnosis of NPC, especially in cases with an occult primary tumour. It may be also of value as a screening test in people at high risk."}
{"id": "PMID:188438", "title": "Cytotoxicity of guinea-pig lymphoid cells against guinea-pig hepatoma cells in tissue culture.", "content": "The cytotoxic effect of guinea-pig lymphoid cells on guinea-pig hepatoma cell lines in tissue culture was investigated, using the microplate technique of Takasugi and Klein (1970). The effect of lymphoid cells from guinea-pigs immunized against tumor cells was compared to that of cells from normal controls. Several ratios of effector to target cells (10 : 1, 50 : 1, 150: 1, 250 : 1) were used. In Hartley guinea-pigs immunized with allogeneic tumour cells, peripheral blood lymphoid cells from 14/16 animals showed significant cytotoxicity against that tumour in culture. In a syngeneic tumour/host system, 7/13 animals showed cytotoxicity. Spleen cells gave less consistent results in both systems. The cytotoxic activity of subpopulations of immune lymphocytes against tumour cells in vitro was investigated. It was found that although both T-cell-enriched and T-cell-depleted cell populations exhibited cytotoxicity against tumour cells, the unfractionated cell population was the most effective. This suggests that some degree of cell cooperation may be involved in the cytotoxicity. Antibody-dependent cellular cytotoxicity was also obtained. A T-cell-depleted population of normal cells was shown to be cytotoxic to tumour cells in the presence of serum from immune animals. This type of cytotoxicity could be obtained concomitantly with cell-mediated cytotoxicity in the same animals.", "contents": "Cytotoxicity of guinea-pig lymphoid cells against guinea-pig hepatoma cells in tissue culture. The cytotoxic effect of guinea-pig lymphoid cells on guinea-pig hepatoma cell lines in tissue culture was investigated, using the microplate technique of Takasugi and Klein (1970). The effect of lymphoid cells from guinea-pigs immunized against tumor cells was compared to that of cells from normal controls. Several ratios of effector to target cells (10 : 1, 50 : 1, 150: 1, 250 : 1) were used. In Hartley guinea-pigs immunized with allogeneic tumour cells, peripheral blood lymphoid cells from 14/16 animals showed significant cytotoxicity against that tumour in culture. In a syngeneic tumour/host system, 7/13 animals showed cytotoxicity. Spleen cells gave less consistent results in both systems. The cytotoxic activity of subpopulations of immune lymphocytes against tumour cells in vitro was investigated. It was found that although both T-cell-enriched and T-cell-depleted cell populations exhibited cytotoxicity against tumour cells, the unfractionated cell population was the most effective. This suggests that some degree of cell cooperation may be involved in the cytotoxicity. Antibody-dependent cellular cytotoxicity was also obtained. A T-cell-depleted population of normal cells was shown to be cytotoxic to tumour cells in the presence of serum from immune animals. This type of cytotoxicity could be obtained concomitantly with cell-mediated cytotoxicity in the same animals."}
{"id": "PMID:188439", "title": "Localization and activity of tissue bound cyclic nucleotide phosphodiesterase in normal and lack of changes in psoriatic human skin.", "content": "This study has been undertaken to elucidate the localization and the activity of cyclic nucleotide phosphodiesterase (PDE) in psoriatic epidermis compared to normal. The results showed that the evaluation of cytochemical methods may be difficult because of the various factors which interfere with the reaction and the considerable amount of background staining. Additionally, only the tissue bound particulate enzyme fraction may be demonstrated by cytochemical means. Nevertheless, the method did reveal that the activity of PDE, if any, is localized on the cytoplasmic membranes of the cells, independent of their origin, and not on the cell surface. Moreover, no differences were found between normal and psoriatic skin. It seems, therefore, that the intracellular degradation of cAMP remains unaltered in psoriasis.", "contents": "Localization and activity of tissue bound cyclic nucleotide phosphodiesterase in normal and lack of changes in psoriatic human skin. This study has been undertaken to elucidate the localization and the activity of cyclic nucleotide phosphodiesterase (PDE) in psoriatic epidermis compared to normal. The results showed that the evaluation of cytochemical methods may be difficult because of the various factors which interfere with the reaction and the considerable amount of background staining. Additionally, only the tissue bound particulate enzyme fraction may be demonstrated by cytochemical means. Nevertheless, the method did reveal that the activity of PDE, if any, is localized on the cytoplasmic membranes of the cells, independent of their origin, and not on the cell surface. Moreover, no differences were found between normal and psoriatic skin. It seems, therefore, that the intracellular degradation of cAMP remains unaltered in psoriasis."}
{"id": "PMID:188440", "title": "Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group.", "content": "A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell-surface markers believed to characterize specific cell types are applied to cases of acute leukaemia. Proposals based on conventional morphological and cytochemical methods are offered following the study of peripheral blood and bone-marrow films from some 200 cases of acute leukaemia by a group of seven French, American and British haematologists. The slides were examined first independently, and then by the group working together. Two groups of acute leukaemia, 'lymphoblastic' and myeloid are further subdivided into three and six groups. Dysmyelopoietic syndromes that may be confused with acute myeloid leukaemia are also considered. Photomicrographs of each of the named conditions are presented.", "contents": "Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell-surface markers believed to characterize specific cell types are applied to cases of acute leukaemia. Proposals based on conventional morphological and cytochemical methods are offered following the study of peripheral blood and bone-marrow films from some 200 cases of acute leukaemia by a group of seven French, American and British haematologists. The slides were examined first independently, and then by the group working together. Two groups of acute leukaemia, 'lymphoblastic' and myeloid are further subdivided into three and six groups. Dysmyelopoietic syndromes that may be confused with acute myeloid leukaemia are also considered. Photomicrographs of each of the named conditions are presented."}
{"id": "PMID:188441", "title": "Relationship of oral contraception to development of trophoblastic tumour after evacuation of a hydatidiform mole.", "content": "The need for chemotherapy for trophoblastic tumour after evacuation of a hydatidiform mole was found to be significantly increased in patients taking oral contraceptives before normal human chorionic gonadotrophin (HCG) values were obtained. Oral contraception was also found to delay the fall in HDG excretion in patients not requiring treatment with cytotoxic drugs.", "contents": "Relationship of oral contraception to development of trophoblastic tumour after evacuation of a hydatidiform mole. The need for chemotherapy for trophoblastic tumour after evacuation of a hydatidiform mole was found to be significantly increased in patients taking oral contraceptives before normal human chorionic gonadotrophin (HCG) values were obtained. Oral contraception was also found to delay the fall in HDG excretion in patients not requiring treatment with cytotoxic drugs."}
{"id": "PMID:188442", "title": "Disruption of Escherichia coli outer membranes by EM 49. A new membrane active peptide.", "content": "A new peptide antibiotic, EM 49, is shown to disrupt the structure of Escherichia coli outer membranes and release outer membrane fragments into the surrounding media. Evidence supporting this conclusion indludes EM 49 stimulated release of outer membrane phospholipids, lipopolysaccharide, and membrane fragments having a phospholipid and polypeptide composition similar to outer membranes. The density of the membrane fragments released by EM 49 was 1.22 g/cm3, which was identical to isolated outer membranes. Approximately 10 to 15% of the E. coli lipopolysaccharide was released upon treatment with EM 49. Both scanning and transmission electron microscopy revealed that the antibiotic caused the formation of numerous protrusions or blebs on the surface of E. coli with apparent release of membrane vesicles from the cells. Direct interaction between EM 49 and outer membranes was demonstrated using outer membranes labeled with the fluorescent dye diphenylhexatriene. Treatment of the fluorescent-labeled outer membranes with EM 49 increased fluorescence intensity and decreased polarization, indicating that the peptide perturbed outer-membrane structure. In addition, strong interactions between EM 49 and purified E. coli phospholipids were detected using the Hummel and Dreyer technique. Association constants between the peptide and phospholipids were approximately 10(5) M-1. A model for the disruptive effect of EM 49 on outer-membrane structure is proposed in which the fatty acid chain of the antibiotic is inserted into the hydrophobic core of the membrane. This orientation would allow the polycationic, peptide portion of the antibiotic to disrupt the antibiotic to disrupt the normal electrostatic interactions between divalent cations and components of the outer membrane. Evidence supporting this conclusion includes specific protection of E. coli from EM 49 by Mg2+ and Ca2+ and inhibition of EM 49 stimulated phospholipid release by these cations. Disruption of the antibiotic to penetrate to the inner membrane, which is probably the primary killing site of EM 49.", "contents": "Disruption of Escherichia coli outer membranes by EM 49. A new membrane active peptide. A new peptide antibiotic, EM 49, is shown to disrupt the structure of Escherichia coli outer membranes and release outer membrane fragments into the surrounding media. Evidence supporting this conclusion indludes EM 49 stimulated release of outer membrane phospholipids, lipopolysaccharide, and membrane fragments having a phospholipid and polypeptide composition similar to outer membranes. The density of the membrane fragments released by EM 49 was 1.22 g/cm3, which was identical to isolated outer membranes. Approximately 10 to 15% of the E. coli lipopolysaccharide was released upon treatment with EM 49. Both scanning and transmission electron microscopy revealed that the antibiotic caused the formation of numerous protrusions or blebs on the surface of E. coli with apparent release of membrane vesicles from the cells. Direct interaction between EM 49 and outer membranes was demonstrated using outer membranes labeled with the fluorescent dye diphenylhexatriene. Treatment of the fluorescent-labeled outer membranes with EM 49 increased fluorescence intensity and decreased polarization, indicating that the peptide perturbed outer-membrane structure. In addition, strong interactions between EM 49 and purified E. coli phospholipids were detected using the Hummel and Dreyer technique. Association constants between the peptide and phospholipids were approximately 10(5) M-1. A model for the disruptive effect of EM 49 on outer-membrane structure is proposed in which the fatty acid chain of the antibiotic is inserted into the hydrophobic core of the membrane. This orientation would allow the polycationic, peptide portion of the antibiotic to disrupt the antibiotic to disrupt the normal electrostatic interactions between divalent cations and components of the outer membrane. Evidence supporting this conclusion includes specific protection of E. coli from EM 49 by Mg2+ and Ca2+ and inhibition of EM 49 stimulated phospholipid release by these cations. Disruption of the antibiotic to penetrate to the inner membrane, which is probably the primary killing site of EM 49."}
{"id": "PMID:188443", "title": "Study of abnormal plasma low-density lipoprotein in rhesus monkeys with diet-induced hyperlipidemia.", "content": "Male rhesus monkeys were divided into three groups: five were fed a regular primate chow diet and were used as controls; four received an \"average\" American diet; and five a special low-fat primate chow diet supplemented with 25% coconut oil and 2% cholesterol. In all of these animals, the plasma low-density lipoproteins (LDL) were isolated by ultracentrifugal flotation between densities of 1.019 and 1.050 g/ml. The LDL of the five control monkeys had variable molecular weights, with a mean value of 3.12 +/- 0.21 X 10(6) (range: 2.92 X 10(6) to 3.45 X 10(6)), and an average partial specific volume of 0.969 +/- 0.003 ml/g; both were assessed by flotation equilibrium analysis in the analytical ultracentrifuge. In the individual animals, however, the physical properties of LDL were invariant with time. The administration of either an \"average\" American diet or a coconut oil-cholesterol diet was accompanied by hypercholesterolemia associated with changes in LDL which were characterized by increases in molecular weight to 3.52 +/- 0.21 X 10(6) (average of nine monkeys) and in partial specific volume to 0.973 +/- 0.002 ml/g. These changes were particularly evident when the molecular weight of LDL from monkeys in the normolipidemic state was compared with that obtained from the same monkeys during the hyperlipidemic state. Chemical analyses revealed that the particles from the hyperlipidemic animals had a relatively higher cholesteryl ester content, a slight increase in phospholipids, and a marked decrease to nearly complete absence of triglycerides. The other lipoprotein components, protein, carbohydrate, free cholesterol, and fatty acids, did not vary significantly from those of control LDL. It is concluded that the administration of atherogenic diets causes structural changes in LDL which appear to be accounted for, at least in part, by changes in the composition of the lipid moiety. The changes in physical and chemical properties noted in the LDL of rhesus monkeys with experimentally induced hypercholesterolemia contrast with the apparent structurally normal LDL from rhesus monkeys with spontaneous hypercholesterolemia reported previously.", "contents": "Study of abnormal plasma low-density lipoprotein in rhesus monkeys with diet-induced hyperlipidemia. Male rhesus monkeys were divided into three groups: five were fed a regular primate chow diet and were used as controls; four received an \"average\" American diet; and five a special low-fat primate chow diet supplemented with 25% coconut oil and 2% cholesterol. In all of these animals, the plasma low-density lipoproteins (LDL) were isolated by ultracentrifugal flotation between densities of 1.019 and 1.050 g/ml. The LDL of the five control monkeys had variable molecular weights, with a mean value of 3.12 +/- 0.21 X 10(6) (range: 2.92 X 10(6) to 3.45 X 10(6)), and an average partial specific volume of 0.969 +/- 0.003 ml/g; both were assessed by flotation equilibrium analysis in the analytical ultracentrifuge. In the individual animals, however, the physical properties of LDL were invariant with time. The administration of either an \"average\" American diet or a coconut oil-cholesterol diet was accompanied by hypercholesterolemia associated with changes in LDL which were characterized by increases in molecular weight to 3.52 +/- 0.21 X 10(6) (average of nine monkeys) and in partial specific volume to 0.973 +/- 0.002 ml/g. These changes were particularly evident when the molecular weight of LDL from monkeys in the normolipidemic state was compared with that obtained from the same monkeys during the hyperlipidemic state. Chemical analyses revealed that the particles from the hyperlipidemic animals had a relatively higher cholesteryl ester content, a slight increase in phospholipids, and a marked decrease to nearly complete absence of triglycerides. The other lipoprotein components, protein, carbohydrate, free cholesterol, and fatty acids, did not vary significantly from those of control LDL. It is concluded that the administration of atherogenic diets causes structural changes in LDL which appear to be accounted for, at least in part, by changes in the composition of the lipid moiety. The changes in physical and chemical properties noted in the LDL of rhesus monkeys with experimentally induced hypercholesterolemia contrast with the apparent structurally normal LDL from rhesus monkeys with spontaneous hypercholesterolemia reported previously."}
{"id": "PMID:188444", "title": "D-Mannitol dehydrogenase from Absidia glauca. Steady-state kinetic properties and the inhibitory role of mannitol 1-phosphate.", "content": "Steady-state kinetic studies including initial velocity for mannitol oxidation and fructose reduction and product inhibition for mannitol oxidation using fructose and reduced nicotinamide adenine dinucleotide (NADH) are in accord with a reaction mechanism best described as ordered Bi-Bi with NAD+ and NADH designated as the first substrate, last product, respectively at pH 8.8. All replots of slopes and intercepts from product inhibition studies were linear. Dead-end inhibition studies using mannitol 1-phosphate gave slope-parabolic, intercept-linear noncompetitive inhibition for both NAD+ and mannitol as substrates. The dead-end inhibitor is capable of binding multiply to the E, EA, and EQ forms of the enzyme to an extent that is controlled by the concentration of substrates. The EQ complex is inferred to undergo a conformational change, E'Q equilibrium EQ, since (V1/E1) greater than (KiqV2)/(KqE1), and no evidence for dead-end complex formation with NADH can be adduced. This is interpreted to mean that the release of fructose from the central complex is faster than the isomerization of the E-NADH complex. When mannitol is saturating, the noncompetitive inhibition against NAD+, as the variable substrate, becomes parabolic uncompetitive. A replot of the slopes of the parabola against mannitol 1-phosphate remains concave upward. This situation could arise if the conformational change we infer in the EQ complex opens up additional sites on the protein which can interact with the dead-end inhibitor.", "contents": "D-Mannitol dehydrogenase from Absidia glauca. Steady-state kinetic properties and the inhibitory role of mannitol 1-phosphate. Steady-state kinetic studies including initial velocity for mannitol oxidation and fructose reduction and product inhibition for mannitol oxidation using fructose and reduced nicotinamide adenine dinucleotide (NADH) are in accord with a reaction mechanism best described as ordered Bi-Bi with NAD+ and NADH designated as the first substrate, last product, respectively at pH 8.8. All replots of slopes and intercepts from product inhibition studies were linear. Dead-end inhibition studies using mannitol 1-phosphate gave slope-parabolic, intercept-linear noncompetitive inhibition for both NAD+ and mannitol as substrates. The dead-end inhibitor is capable of binding multiply to the E, EA, and EQ forms of the enzyme to an extent that is controlled by the concentration of substrates. The EQ complex is inferred to undergo a conformational change, E'Q equilibrium EQ, since (V1/E1) greater than (KiqV2)/(KqE1), and no evidence for dead-end complex formation with NADH can be adduced. This is interpreted to mean that the release of fructose from the central complex is faster than the isomerization of the E-NADH complex. When mannitol is saturating, the noncompetitive inhibition against NAD+, as the variable substrate, becomes parabolic uncompetitive. A replot of the slopes of the parabola against mannitol 1-phosphate remains concave upward. This situation could arise if the conformational change we infer in the EQ complex opens up additional sites on the protein which can interact with the dead-end inhibitor."}
{"id": "PMID:188445", "title": "Isolation and characterization of DNA-DNA and DNA-RNA.", "content": "A simple method for the isolation and characterization of DNA-DNA and DNA-RNA hybrid molecules formed in solution was developed. It was based on the fact that, in appropriate salt concentration, such as 5% Na2HPO4, DNA in either double-stranded (DNA-DNA or DNA-RNA) or single-stranded forms, but not free nucleotides, can bind to diethylaminoethylcellulose disc filters (DE81). Thus tested samples were treated with the single-strand-specific nuclease S1 and then applied to DE81 filters. The free nucleotides, resulting from degrading the single-stranded molecules, were removed by intensive washing with 5% Na2HPO4, leaving only the hybrid molecules on the filters. The usefulness of this method was illustrated in dissociation and reassociation studies of viral (SV40) or cellular (NIH/3T3) DNAs and DNA-RNA hybrid molecules. Using this technique the reassociation of denatured SV40 DNA was found to be a very rapid process. Dissociation studies revealed that the melting curves of tested DNAs were dependent on salt concentration. Thus the melting temperatures (tm) obtained for SV40 DNA were 76 degrees C at 1 X SSC (0.15 M NaCl-0.015 M sodium citrate) and 65 degrees C at 0.1 X SSC, and for NIH/3T3 DNA 82 degrees C at 1 X SSC and 68 degrees C at 0.1 X SSC. MuLV DNA-RNA hybrid molecules were formed by annealing in vitro synthesized MuLV DNA with 70S MuLV RNA at 68 degrees C. The melting temperature of this hybrid in the annealing solution was 87 degrees C. Another important feature of this procedure was that, after being selectively bound to the filters, the hybrid molecules could efficiently be recovered by heating the filters for 5 min at 60 degrees C in 1.5-1.7 M KCl. The recovered molecules were intact hybrids as they were found to be completely resistant to S1 nuclease.", "contents": "Isolation and characterization of DNA-DNA and DNA-RNA. A simple method for the isolation and characterization of DNA-DNA and DNA-RNA hybrid molecules formed in solution was developed. It was based on the fact that, in appropriate salt concentration, such as 5% Na2HPO4, DNA in either double-stranded (DNA-DNA or DNA-RNA) or single-stranded forms, but not free nucleotides, can bind to diethylaminoethylcellulose disc filters (DE81). Thus tested samples were treated with the single-strand-specific nuclease S1 and then applied to DE81 filters. The free nucleotides, resulting from degrading the single-stranded molecules, were removed by intensive washing with 5% Na2HPO4, leaving only the hybrid molecules on the filters. The usefulness of this method was illustrated in dissociation and reassociation studies of viral (SV40) or cellular (NIH/3T3) DNAs and DNA-RNA hybrid molecules. Using this technique the reassociation of denatured SV40 DNA was found to be a very rapid process. Dissociation studies revealed that the melting curves of tested DNAs were dependent on salt concentration. Thus the melting temperatures (tm) obtained for SV40 DNA were 76 degrees C at 1 X SSC (0.15 M NaCl-0.015 M sodium citrate) and 65 degrees C at 0.1 X SSC, and for NIH/3T3 DNA 82 degrees C at 1 X SSC and 68 degrees C at 0.1 X SSC. MuLV DNA-RNA hybrid molecules were formed by annealing in vitro synthesized MuLV DNA with 70S MuLV RNA at 68 degrees C. The melting temperature of this hybrid in the annealing solution was 87 degrees C. Another important feature of this procedure was that, after being selectively bound to the filters, the hybrid molecules could efficiently be recovered by heating the filters for 5 min at 60 degrees C in 1.5-1.7 M KCl. The recovered molecules were intact hybrids as they were found to be completely resistant to S1 nuclease."}
{"id": "PMID:188446", "title": "Fidelity of ribosomal ribonucleic acid synthesis by nucleoli and nucleolar chromatin.", "content": "Isolated nucleoli, nucleolar chromatin, and nucleolar DNA were used as templates for DNA synthesis in appropriately supplemented systems in which RNA polymerases other than RNA polymerase I were blocked by alpha-amanitin. With the aid of nucleotide analysis, DNA-RNA hybridization, and homochromatography fingerprinting, it was found that isolated nucleoli and nucleolar chromatin serve primarily as templates for synthesis of rRNA. However, the products formed with purified nucleolar DNA as a template do not contain the specific rRNA oligonucleotides nor are they appreciably hybridized to the rDNA region on cesium chloride gradients. These results indicate that whole nucleoli and nucleolar chromatin contain control mechanisms that restrict readouts by RNA polymerase I of nucleolar DNA to rDNA.", "contents": "Fidelity of ribosomal ribonucleic acid synthesis by nucleoli and nucleolar chromatin. Isolated nucleoli, nucleolar chromatin, and nucleolar DNA were used as templates for DNA synthesis in appropriately supplemented systems in which RNA polymerases other than RNA polymerase I were blocked by alpha-amanitin. With the aid of nucleotide analysis, DNA-RNA hybridization, and homochromatography fingerprinting, it was found that isolated nucleoli and nucleolar chromatin serve primarily as templates for synthesis of rRNA. However, the products formed with purified nucleolar DNA as a template do not contain the specific rRNA oligonucleotides nor are they appreciably hybridized to the rDNA region on cesium chloride gradients. These results indicate that whole nucleoli and nucleolar chromatin contain control mechanisms that restrict readouts by RNA polymerase I of nucleolar DNA to rDNA."}
{"id": "PMID:188447", "title": "On the location of the divalent metal binding sites and the light chain subunits of vertebrate myosin.", "content": "The divalent metal ion binding sites of skeletal myosin were investigated by electron paramagnetic resonance (EPR) spectroscopy using the paramagnetic (Mn(II) ion as a probe. Myosin possesses two high affinity sites (K less than 1 muM) for Mn(II), which are located on the 5,5'-dithiobis(2-nitrobenzoate) (DTNB) light chains. Mn(II) bound to the isolated DTNB light chain gives rise to an EPR spectrum similar to that of Mn(II) bound to myosin and this indicates that the metal binding site comprises ligands from the DTNB light chain alone. Myosin preparations in which the DTNB light chain content is reduced by treatment with 5,5'-dithiobis(2-nitrobenzoate) show a corresponding reduction in the stoichiometry of Mn(II) binding, but the stoichiometry is recovered on reassociation of the DTNB light chain. Chymotryptic digestion of myosin filaments in the presence of ethylenediaminetetraacetic acid yields subfragment 1, but digestion in the presence of divalent metal ions produces heavy meromyosin. Myosin with a depleted DTNB light chain content gives rise to subfragment 1 on proteolysis, even in the presence of divalent metal ions. It is proposed that saturation of the DTNB light chain site with divalent ions protects this subunit against proteolysis, which, in turn, inhibits the cleavage of the subfragment 1-subfragment 2 link. Either the DTNB light chain is located near the region of the link and sterically blocks chymotryptic attack, or it is bound to the subfragment 1 moiety and affects the conformation of the link region. When the product heavy meromyosin was examined by sodium dodecyl sulfate gel electrophoresis, an apparent anomaly arose in that there was no trace of the 19 000-dalton band corresponding to the DTNB light chain. This was resolved by following the time course of chymotryptic digestion of the myosin heavy chain, the DTNB light chain, and the divalent metal binding site. The 19 000-dalton DTNB light chain is rapidly degraded to a 17 000-dalton fragment which comigrates with the alkali 2 light chain. The divalent metal site remains intact, despite this degradation, and the 17 000 fragment continues to protect the subfragment 1-subfragment 2 link. In the absence of divalent metal ions, the 17 000-dalton fragment is further degraded and attack of the subfragment 1 link ensues. Mn(II) bound to cardiac myosin gives an EPR spectrum basically similar to that of skeletal myosin, suggesting that their 19 000-dalton light chains are analogous with respect to their divalent metal binding sites, despite their chemical differences. The potential of EPR spectroscopy for characterizing the metal binding sites of myosin from different sources and of intact muscle fibers is discussed.", "contents": "On the location of the divalent metal binding sites and the light chain subunits of vertebrate myosin. The divalent metal ion binding sites of skeletal myosin were investigated by electron paramagnetic resonance (EPR) spectroscopy using the paramagnetic (Mn(II) ion as a probe. Myosin possesses two high affinity sites (K less than 1 muM) for Mn(II), which are located on the 5,5'-dithiobis(2-nitrobenzoate) (DTNB) light chains. Mn(II) bound to the isolated DTNB light chain gives rise to an EPR spectrum similar to that of Mn(II) bound to myosin and this indicates that the metal binding site comprises ligands from the DTNB light chain alone. Myosin preparations in which the DTNB light chain content is reduced by treatment with 5,5'-dithiobis(2-nitrobenzoate) show a corresponding reduction in the stoichiometry of Mn(II) binding, but the stoichiometry is recovered on reassociation of the DTNB light chain. Chymotryptic digestion of myosin filaments in the presence of ethylenediaminetetraacetic acid yields subfragment 1, but digestion in the presence of divalent metal ions produces heavy meromyosin. Myosin with a depleted DTNB light chain content gives rise to subfragment 1 on proteolysis, even in the presence of divalent metal ions. It is proposed that saturation of the DTNB light chain site with divalent ions protects this subunit against proteolysis, which, in turn, inhibits the cleavage of the subfragment 1-subfragment 2 link. Either the DTNB light chain is located near the region of the link and sterically blocks chymotryptic attack, or it is bound to the subfragment 1 moiety and affects the conformation of the link region. When the product heavy meromyosin was examined by sodium dodecyl sulfate gel electrophoresis, an apparent anomaly arose in that there was no trace of the 19 000-dalton band corresponding to the DTNB light chain. This was resolved by following the time course of chymotryptic digestion of the myosin heavy chain, the DTNB light chain, and the divalent metal binding site. The 19 000-dalton DTNB light chain is rapidly degraded to a 17 000-dalton fragment which comigrates with the alkali 2 light chain. The divalent metal site remains intact, despite this degradation, and the 17 000 fragment continues to protect the subfragment 1-subfragment 2 link. In the absence of divalent metal ions, the 17 000-dalton fragment is further degraded and attack of the subfragment 1 link ensues. Mn(II) bound to cardiac myosin gives an EPR spectrum basically similar to that of skeletal myosin, suggesting that their 19 000-dalton light chains are analogous with respect to their divalent metal binding sites, despite their chemical differences. The potential of EPR spectroscopy for characterizing the metal binding sites of myosin from different sources and of intact muscle fibers is discussed."}
{"id": "PMID:188449", "title": "Near-neighbor relationships of the subunits of cytochrome c oxidase.", "content": "Cytochrome c oxidase in detergent dispersion has been cross-linked with two reversible cross-linking agents, dithiobissuccinimidylpropionate (DSP) and dimethyl-3,3'-dithiobispropionimidate (DTBP), and the cross-linked products formed have been analyzed by two-dimensional gel electrophoresis. Under mild reaction conditions, several subunit pairs were seen including II and V, V and VII, IV and VI. With higher levels of DSP, larger aggregates were seen until a cross-linked product with an apparent molecular weight of 140 000 was the predominant band on gels. This is the smallest molecular weight aggregate to contain all seven subunits of the enzyme and most likely represents the \"unit\" or two heme and two copper containing complex of cytochrome c oxidase.", "contents": "Near-neighbor relationships of the subunits of cytochrome c oxidase. Cytochrome c oxidase in detergent dispersion has been cross-linked with two reversible cross-linking agents, dithiobissuccinimidylpropionate (DSP) and dimethyl-3,3'-dithiobispropionimidate (DTBP), and the cross-linked products formed have been analyzed by two-dimensional gel electrophoresis. Under mild reaction conditions, several subunit pairs were seen including II and V, V and VII, IV and VI. With higher levels of DSP, larger aggregates were seen until a cross-linked product with an apparent molecular weight of 140 000 was the predominant band on gels. This is the smallest molecular weight aggregate to contain all seven subunits of the enzyme and most likely represents the \"unit\" or two heme and two copper containing complex of cytochrome c oxidase."}
{"id": "PMID:188450", "title": "Topographic distribution of enzymes involved in glycerolipid synthesis in rat small, intestinal epithelium.", "content": "1. The enzymes involved in glycerolphosphate and monoacylglycerol acylation of rat small intestine were more active in villi than in crypts. Monoglyceride acyltransferase (EC 2.3.1.22) was found to be absent from crypts. 2. In the villi, the enzymes are mainly localized in microsomes, although low activities of palmitoyl-CoA synthetase (EC 6.2.1.3), glycerolphosphate acyltransferase (EC 2.3.1.15) and cholinephosphotransferase (EC 2.7.8.2) are found in mitochondria. Mitochondria lack monoglyceride acyltransferase and lysolecithin acyltransferase (EC 2.3.1.23), both of which are involved in the reacylation of alimentary partial glycerides. Therefore, this process is confined to microsomes. 3. The monoacylglycerol and lysolecithin acyltransferases, as well as choline-phosphotransferase, are probably localized within the endoplasmic reticulum, since these enzymes are relatively Nagerse resistant (subtilisin; EC 3.4.2.1, compared with palmitoyl-CoA synthetase and glycerolphosphate acyltransferase, which are highly Nagarse-sensitive and therefore probably localized on the outside of the microsomes (and mitochondria). 4. The physical separation of alimentary product reacylation from de novo synthetic processes provides the basis of metabolic compartmentation observed by other workers. 5. The use of sucrose instead of a salt medium for the isolation and homogenization of small intestinal epithelial cells allowed the separation of mitochondria and microsomes by differential centrifugation without mutual contamination. 6. Phospholipids were found to stimulate glycerolphosphate acylation in vitro. 7. The glycerolphosphate and monoacylglycerol acylation pathways are not competitive.", "contents": "Topographic distribution of enzymes involved in glycerolipid synthesis in rat small, intestinal epithelium. 1. The enzymes involved in glycerolphosphate and monoacylglycerol acylation of rat small intestine were more active in villi than in crypts. Monoglyceride acyltransferase (EC 2.3.1.22) was found to be absent from crypts. 2. In the villi, the enzymes are mainly localized in microsomes, although low activities of palmitoyl-CoA synthetase (EC 6.2.1.3), glycerolphosphate acyltransferase (EC 2.3.1.15) and cholinephosphotransferase (EC 2.7.8.2) are found in mitochondria. Mitochondria lack monoglyceride acyltransferase and lysolecithin acyltransferase (EC 2.3.1.23), both of which are involved in the reacylation of alimentary partial glycerides. Therefore, this process is confined to microsomes. 3. The monoacylglycerol and lysolecithin acyltransferases, as well as choline-phosphotransferase, are probably localized within the endoplasmic reticulum, since these enzymes are relatively Nagerse resistant (subtilisin; EC 3.4.2.1, compared with palmitoyl-CoA synthetase and glycerolphosphate acyltransferase, which are highly Nagarse-sensitive and therefore probably localized on the outside of the microsomes (and mitochondria). 4. The physical separation of alimentary product reacylation from de novo synthetic processes provides the basis of metabolic compartmentation observed by other workers. 5. The use of sucrose instead of a salt medium for the isolation and homogenization of small intestinal epithelial cells allowed the separation of mitochondria and microsomes by differential centrifugation without mutual contamination. 6. Phospholipids were found to stimulate glycerolphosphate acylation in vitro. 7. The glycerolphosphate and monoacylglycerol acylation pathways are not competitive."}
{"id": "PMID:188451", "title": "Influence of lysophosphatidylcholine on the metabolism of plasma lipoproteins.", "content": "Both low density lipoproteins and cellular membranes are known to have a high affinity for lysophosphatidylcholine. In this study lysophosphatidylcholine influenced the retention of lipoproteins by arterial tissue in vitro and the rate of disappearance of low density lipoproteins from the blood in vivo. Pieces of aorta from rabbits or rhesus monkeys were successively incubated for 90 min each in 2 or 3 solutions. After the last incubation the intima plus inner media was dissected from the remainder of the aorta for analysis. The second incubation always contained lipoproteins labeled with [3H]leucine. When lysophosphaticylcholine was included in the first but not in the second incubation fluid, the retention of low, or high density lipoproteins by the intima plus inner media increased. A subsequent incubation of the piece of artery in a fluid with trypsin or lysophosphatidylcholine caused a release of some of the lipoproteins. Lysophosphatidylcholine was bound simultaneously by plasma low density lipoproteins and vascular tissue in vitro and appeared to promote the association of the latter two components. When lysophosphatidylcholine equal to 2--10 times the usual total intravascular content was injected intravenously into control squirrel monkeys or rabbits, it was rapidly cleared from the blood. On the other hand, injected lysophosphatidylcholine persisted in the blood of hyperlipoproteinemic rabbits and was associated with the low density lipoproteins. In control animals, the injection of lysophosphatidylcholine was associated with an increase in the rate of removal of 125I-labelled low density lipoprotein from plasma and of its appearance in liver.", "contents": "Influence of lysophosphatidylcholine on the metabolism of plasma lipoproteins. Both low density lipoproteins and cellular membranes are known to have a high affinity for lysophosphatidylcholine. In this study lysophosphatidylcholine influenced the retention of lipoproteins by arterial tissue in vitro and the rate of disappearance of low density lipoproteins from the blood in vivo. Pieces of aorta from rabbits or rhesus monkeys were successively incubated for 90 min each in 2 or 3 solutions. After the last incubation the intima plus inner media was dissected from the remainder of the aorta for analysis. The second incubation always contained lipoproteins labeled with [3H]leucine. When lysophosphaticylcholine was included in the first but not in the second incubation fluid, the retention of low, or high density lipoproteins by the intima plus inner media increased. A subsequent incubation of the piece of artery in a fluid with trypsin or lysophosphatidylcholine caused a release of some of the lipoproteins. Lysophosphatidylcholine was bound simultaneously by plasma low density lipoproteins and vascular tissue in vitro and appeared to promote the association of the latter two components. When lysophosphatidylcholine equal to 2--10 times the usual total intravascular content was injected intravenously into control squirrel monkeys or rabbits, it was rapidly cleared from the blood. On the other hand, injected lysophosphatidylcholine persisted in the blood of hyperlipoproteinemic rabbits and was associated with the low density lipoproteins. In control animals, the injection of lysophosphatidylcholine was associated with an increase in the rate of removal of 125I-labelled low density lipoprotein from plasma and of its appearance in liver."}
{"id": "PMID:188452", "title": "The influence of LP-X and other lipoproteins associated with hepatic dysfunction on the activity of lecithin:cholesterol acyltransferase.", "content": "A study was made of the in vitro effects of the abnormal serum lipoproteins associated with liver disease on the activity of the enzyme lecithin:cholesterol acyltransferase. At lipoprotein concentrations equivalent to those found in hepatic disease sera, the results indicate that: (1) LP-X levels greater than 2.5 mg/ml produced total inhibition of enzyme activity. (2) LP-X levels remained constant even up to 36 h incubation, despite active cholesterol esterification in the presence of LP-X concentrations less than 2.5 mg/ml. In addition, the specific activity of radiolabelled LP-X, and its electrophoretic properties remained unchanged after incubation showing that the molecule remained intact. (3) Low density lipoproteins other than LP-X stimulated the enzymes activity, but this effect was overcome by LP-X. (4) Additional concentrations of high density lipoproteins also produced enhancement of enzyme activity, but at higher levels inhibition was seen. LP-X prevented the enhancement of lecithin:cholesterol acyltransferase activity. (5) Small samples of pure LP-X, obtained with the minimum of physical manipulation, showed a complete absence of cholesterol ester and triacylglycerol from the molecule. The implications of these results are discussed, particularly in relation to other reports which have presented evidence that LP-X is a substrate for lecithin:cholesterol acyltransferase.", "contents": "The influence of LP-X and other lipoproteins associated with hepatic dysfunction on the activity of lecithin:cholesterol acyltransferase. A study was made of the in vitro effects of the abnormal serum lipoproteins associated with liver disease on the activity of the enzyme lecithin:cholesterol acyltransferase. At lipoprotein concentrations equivalent to those found in hepatic disease sera, the results indicate that: (1) LP-X levels greater than 2.5 mg/ml produced total inhibition of enzyme activity. (2) LP-X levels remained constant even up to 36 h incubation, despite active cholesterol esterification in the presence of LP-X concentrations less than 2.5 mg/ml. In addition, the specific activity of radiolabelled LP-X, and its electrophoretic properties remained unchanged after incubation showing that the molecule remained intact. (3) Low density lipoproteins other than LP-X stimulated the enzymes activity, but this effect was overcome by LP-X. (4) Additional concentrations of high density lipoproteins also produced enhancement of enzyme activity, but at higher levels inhibition was seen. LP-X prevented the enhancement of lecithin:cholesterol acyltransferase activity. (5) Small samples of pure LP-X, obtained with the minimum of physical manipulation, showed a complete absence of cholesterol ester and triacylglycerol from the molecule. The implications of these results are discussed, particularly in relation to other reports which have presented evidence that LP-X is a substrate for lecithin:cholesterol acyltransferase."}
{"id": "PMID:188453", "title": "M\u00f6ssbauer spectroscopic study of compound ES of cytochrome c peroxidase.", "content": "M\u00f6ssbauer spectra of Compound ES of cytochrome c peroxidase have been observed over a range of temperature and applied magnetic field. These have been interpreted in terms of a crystal field model of the iron site in which the iron is assumed to be in the Fe(IV) state with unpaired spin S = 1. Detailed least-squares fitting of the spectra fitting of the spectra indicates that both the electric field gradient choice of a single parameter, the axial crystal field, the magnetic properties are well reproduced. The model also provides the observed positive sign for the electric field gradient interaction, but overestimates its magnitude. This apparent discrepnancy may be caused by the presence of significant electronic charge in filled bonding orbitals, a feature which is in keeping with expected covalent charge compensation of the extreme oxidation state. There is no evidence in the M\u00f6ssbauer spectra of interaction between the iron and the ESR-visible free radical. This suggests they are well separated.", "contents": "M\u00f6ssbauer spectroscopic study of compound ES of cytochrome c peroxidase. M\u00f6ssbauer spectra of Compound ES of cytochrome c peroxidase have been observed over a range of temperature and applied magnetic field. These have been interpreted in terms of a crystal field model of the iron site in which the iron is assumed to be in the Fe(IV) state with unpaired spin S = 1. Detailed least-squares fitting of the spectra fitting of the spectra indicates that both the electric field gradient choice of a single parameter, the axial crystal field, the magnetic properties are well reproduced. The model also provides the observed positive sign for the electric field gradient interaction, but overestimates its magnitude. This apparent discrepnancy may be caused by the presence of significant electronic charge in filled bonding orbitals, a feature which is in keeping with expected covalent charge compensation of the extreme oxidation state. There is no evidence in the M\u00f6ssbauer spectra of interaction between the iron and the ESR-visible free radical. This suggests they are well separated."}
{"id": "PMID:188454", "title": "The decreased synthesis of chondroitin sulfate-containing extracellular proteoglycans by SV40 transformed Balb/c 3T3 cells.", "content": "Balb/c 3T3 cells synthesize 5--10 times more 35SO2/4- -labeled extracellular proteoglycan per cell than do Balb/c 3T3 cells transformed by SV40 (SV3T3). The extracellular 35SO2/4- -labeled proteoglycans of the Balb/c 3T3 and SV3T3 cells differ markedly in their acid mucopolysaccharide composition. Extracellular Balb/c 3T3 proteoglycans contain about 70--80% chondroitin sulfate, most of which is chondroitin 4-sulfate, and small amounts of heparan sulfate and/or heparin. On the other hand, extracellular SV3T3 proteoglycans contain 65-75% heparan sulfate and/or heparin and less than 15% chondroitin sulfate. Analysis of extracellular 35SO2/4- -labeled proteoglycan by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals that Balb/c 3T3 alone synthesizes a class of proteoglycans capable of migrating in a 10% separating gel. This class of proteoglycans, designated as fraction C, accounts for up to 45% of the total extracellular Balb/c 3T3 35 SO2/4- -labeled proteoglycans and contains chondroitin sulfate extracellular SV3T3 proteoglycans. The absence of this and other classes of chondroitin sulfate-containing proteoglycans can account for the 5-10-fold decreased synthesis of 35SO2/4- -labeled proteoglycans by SV3T3 cells when compared to Balb/c 3T3 cells.", "contents": "The decreased synthesis of chondroitin sulfate-containing extracellular proteoglycans by SV40 transformed Balb/c 3T3 cells. Balb/c 3T3 cells synthesize 5--10 times more 35SO2/4- -labeled extracellular proteoglycan per cell than do Balb/c 3T3 cells transformed by SV40 (SV3T3). The extracellular 35SO2/4- -labeled proteoglycans of the Balb/c 3T3 and SV3T3 cells differ markedly in their acid mucopolysaccharide composition. Extracellular Balb/c 3T3 proteoglycans contain about 70--80% chondroitin sulfate, most of which is chondroitin 4-sulfate, and small amounts of heparan sulfate and/or heparin. On the other hand, extracellular SV3T3 proteoglycans contain 65-75% heparan sulfate and/or heparin and less than 15% chondroitin sulfate. Analysis of extracellular 35SO2/4- -labeled proteoglycan by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals that Balb/c 3T3 alone synthesizes a class of proteoglycans capable of migrating in a 10% separating gel. This class of proteoglycans, designated as fraction C, accounts for up to 45% of the total extracellular Balb/c 3T3 35 SO2/4- -labeled proteoglycans and contains chondroitin sulfate extracellular SV3T3 proteoglycans. The absence of this and other classes of chondroitin sulfate-containing proteoglycans can account for the 5-10-fold decreased synthesis of 35SO2/4- -labeled proteoglycans by SV3T3 cells when compared to Balb/c 3T3 cells."}
{"id": "PMID:188455", "title": "Extracellular metabolism of cyclic AMP.", "content": "Intravenously administered cyclic [8-3H]AMP to rats was quickly eliminated from the circulation. After 2 min 93% of the administered radioactivity disappeared from the plasues was recovered mainly in the form of nucleotides, ATP, ADP, AMP and IMP. In vitro contact of cyclic AMP with perfused liver, isolated liver cells and adipose tissue resulted in a rapid breakdown of the nucleotide, presumably on the outer surface of the cells. The degradation products have been identified mainly as adenosine and inosine. Incubation of adipose tissue and isolated liver cells with [3H] AMP also resulted in the breakdown of the nucleotide in themedium. The rate of AMP degradation by these tissues was faster than that for cyclic AMP degradation. The data suggest that cyclic AMP is readily metabolized on the outer surface of cells to products which may be converted within the cells to nucleotides. These findings seem of importance for the quantitative assessments of cellular cyclic AMP outflow during hormonal stimulation.", "contents": "Extracellular metabolism of cyclic AMP. Intravenously administered cyclic [8-3H]AMP to rats was quickly eliminated from the circulation. After 2 min 93% of the administered radioactivity disappeared from the plasues was recovered mainly in the form of nucleotides, ATP, ADP, AMP and IMP. In vitro contact of cyclic AMP with perfused liver, isolated liver cells and adipose tissue resulted in a rapid breakdown of the nucleotide, presumably on the outer surface of the cells. The degradation products have been identified mainly as adenosine and inosine. Incubation of adipose tissue and isolated liver cells with [3H] AMP also resulted in the breakdown of the nucleotide in themedium. The rate of AMP degradation by these tissues was faster than that for cyclic AMP degradation. The data suggest that cyclic AMP is readily metabolized on the outer surface of cells to products which may be converted within the cells to nucleotides. These findings seem of importance for the quantitative assessments of cellular cyclic AMP outflow during hormonal stimulation."}
{"id": "PMID:188456", "title": "Cyclic AMP metabolism in mouse parotid glands. Properties of adenylate cyclase, protein kinase and phosphodiesterase.", "content": "Catecholamines induce unique growth and secretory responses in salivary glands. An analysis of three enzyme activities involved in cyclic AMP metabolism was carried out to identify the specificity of these responses for salivary glands. Although parotid adenylate cyclase has an unusually high specific activity, its kinetic properties and responses to NaF, guanine nucleotides, and isoproterenol are similar to other tissues not stimulated to grow after isoproterenol stimulation. Solubilized adenylate cyclase was separated from other membrane proteins by isoelectric focusing on polyacrylamide gels. There was a single broad peak of activity witha pI of 5.9. Parotid protein kinase has a subcellular distribution and substrate preference similar to hepatic protein kinase. Activation by cyclic AMP is also similar to that reported for other tissues, with a Ka of 1.2 - 10(-7) M. Parotid cyclic AMP and cyclic GMP phosphodiesterases are a heterogeneous group of enzymes with relatively low specific activity as compared with mouse pancreas, liver and brain. Isoelectric focusing of supernatant phosphodiesterases revealed at least sixpeaks of enzyme activity in the pI range of 4-6. Previous reports of a large increase in parotid cyclic  AMP levels after in vivo administration of catecholamines and specific growth and secretion could be the result of a relatively high specific activity adenylate cyclase associated with low specific activity cyclic AMP phosphodiesterases.", "contents": "Cyclic AMP metabolism in mouse parotid glands. Properties of adenylate cyclase, protein kinase and phosphodiesterase. Catecholamines induce unique growth and secretory responses in salivary glands. An analysis of three enzyme activities involved in cyclic AMP metabolism was carried out to identify the specificity of these responses for salivary glands. Although parotid adenylate cyclase has an unusually high specific activity, its kinetic properties and responses to NaF, guanine nucleotides, and isoproterenol are similar to other tissues not stimulated to grow after isoproterenol stimulation. Solubilized adenylate cyclase was separated from other membrane proteins by isoelectric focusing on polyacrylamide gels. There was a single broad peak of activity witha pI of 5.9. Parotid protein kinase has a subcellular distribution and substrate preference similar to hepatic protein kinase. Activation by cyclic AMP is also similar to that reported for other tissues, with a Ka of 1.2 - 10(-7) M. Parotid cyclic AMP and cyclic GMP phosphodiesterases are a heterogeneous group of enzymes with relatively low specific activity as compared with mouse pancreas, liver and brain. Isoelectric focusing of supernatant phosphodiesterases revealed at least sixpeaks of enzyme activity in the pI range of 4-6. Previous reports of a large increase in parotid cyclic  AMP levels after in vivo administration of catecholamines and specific growth and secretion could be the result of a relatively high specific activity adenylate cyclase associated with low specific activity cyclic AMP phosphodiesterases."}
{"id": "PMID:188457", "title": "The interaction between water and the polar head in inverted phosphatidylcholine micelles. A 2H and 31P relaxation study.", "content": "2H and 31P spin-lattice relaxation times (T1) were studied for inverted egg phosphatidylcholine micelles in CCl4 as functions of 2H2O concentration. When the 2h2O/phosphatidylcholine mole ratio changed from 1.0 to 18.0, T1 of 31P increased by about 2.6 fold, whereas T1 of 2H increased by about 50 fold. A quantitative analysis of the deuterium T1 data showed that there is only one water molecule tightly bound to the polar head, and it is in rapid exchange with the rest of the water molecules. The activation  energy for the deuterium T1 was 7.1 +/- 0.8 kcal/mol(30 +/- 3 kJ/mol), and was independent of the 2H2O concentration.", "contents": "The interaction between water and the polar head in inverted phosphatidylcholine micelles. A 2H and 31P relaxation study. 2H and 31P spin-lattice relaxation times (T1) were studied for inverted egg phosphatidylcholine micelles in CCl4 as functions of 2H2O concentration. When the 2h2O/phosphatidylcholine mole ratio changed from 1.0 to 18.0, T1 of 31P increased by about 2.6 fold, whereas T1 of 2H increased by about 50 fold. A quantitative analysis of the deuterium T1 data showed that there is only one water molecule tightly bound to the polar head, and it is in rapid exchange with the rest of the water molecules. The activation  energy for the deuterium T1 was 7.1 +/- 0.8 kcal/mol(30 +/- 3 kJ/mol), and was independent of the 2H2O concentration."}
{"id": "PMID:188458", "title": "Effects of adenosine and its derivatives on protein kinase activity of beef thyroid.", "content": "Effects of adenosine and some of its derivatives on beef protein kinase activity were investigated in vitro. Adenosine rapidly inhibited protein kinase activity in a dose-dependent manner. Significant inhibition occurred with 10 muM and half-maximal inhibition at 100 muM adenosine. Inhibition was almost complete with 5 mM adenosine. Inhibition was similar whether protein kinase activity was assayed with or without cyclic AMP. The inhibition  by adenosine was reversed by increasing the concentration of ATP and Lineweaver-Burk analysis indicated that adenosine inhibition was competitive with ATP. Addition of adenosine deaminase to the incubation medium prevented the inhibition induced by adenosine. Intact 1 and N6 positions of adenosine were important for the inhibition since their modification was associated with loss of inhibition. Modification of the 8 position of adenosine decreased, but did not abolish, the inhibition. The 2 and 3 position of ribose did not seem to be critical since 2- and 3-deoxyadenosine produced inhibition similar to that of adenosine.", "contents": "Effects of adenosine and its derivatives on protein kinase activity of beef thyroid. Effects of adenosine and some of its derivatives on beef protein kinase activity were investigated in vitro. Adenosine rapidly inhibited protein kinase activity in a dose-dependent manner. Significant inhibition occurred with 10 muM and half-maximal inhibition at 100 muM adenosine. Inhibition was almost complete with 5 mM adenosine. Inhibition was similar whether protein kinase activity was assayed with or without cyclic AMP. The inhibition  by adenosine was reversed by increasing the concentration of ATP and Lineweaver-Burk analysis indicated that adenosine inhibition was competitive with ATP. Addition of adenosine deaminase to the incubation medium prevented the inhibition induced by adenosine. Intact 1 and N6 positions of adenosine were important for the inhibition since their modification was associated with loss of inhibition. Modification of the 8 position of adenosine decreased, but did not abolish, the inhibition. The 2 and 3 position of ribose did not seem to be critical since 2- and 3-deoxyadenosine produced inhibition similar to that of adenosine."}
{"id": "PMID:188459", "title": "Subcellular location of adenylate cyclase in rat cardiac muscle.", "content": "Crude homogenates of rat cardiac muscle were fractionated in order to examine the subcellular location of adenylate cyclase in this tissue. The fractionation procedure employed differential centrifugation of homogenized material followed by collagenase treatment, centrifugation on a discontinuous sucrose density gradient and extraction with 1 M KCl. The particulate fraction obtained by this procedure contained a high specific activity and yield of adenylate cyclase, moderate levels of mitochondria and low levels of sarcoplasmic reticulum and contractile protein as judged by marker enzyme activities. Adenylate cyclase was purified 20-fold with a 33% yield from the crude homogenate, while mitochondrial, sarcoplasmic reticulum and contractile protein yields were 5, 0.4 and 0.7% respectively. The membrane fractions prepared in this manner were examined by sodium dodecyl sulfate - gel electro phoresis. Adenylate cyclase copurfied with ouabain-sensitive (Na+ + K+)-ATPase, a plasma membrane marker enzyme, and not with Ca2+ -accumulating activity, which is associated with the sarcoplasmic reticulum. The distribution of marker enzyme activities indicates that heart adenylate cyclase is not located in the sarcoplasmic reticulum but is localized predominantly, if not exclusively, in the plasma membrane.", "contents": "Subcellular location of adenylate cyclase in rat cardiac muscle. Crude homogenates of rat cardiac muscle were fractionated in order to examine the subcellular location of adenylate cyclase in this tissue. The fractionation procedure employed differential centrifugation of homogenized material followed by collagenase treatment, centrifugation on a discontinuous sucrose density gradient and extraction with 1 M KCl. The particulate fraction obtained by this procedure contained a high specific activity and yield of adenylate cyclase, moderate levels of mitochondria and low levels of sarcoplasmic reticulum and contractile protein as judged by marker enzyme activities. Adenylate cyclase was purified 20-fold with a 33% yield from the crude homogenate, while mitochondrial, sarcoplasmic reticulum and contractile protein yields were 5, 0.4 and 0.7% respectively. The membrane fractions prepared in this manner were examined by sodium dodecyl sulfate - gel electro phoresis. Adenylate cyclase copurfied with ouabain-sensitive (Na+ + K+)-ATPase, a plasma membrane marker enzyme, and not with Ca2+ -accumulating activity, which is associated with the sarcoplasmic reticulum. The distribution of marker enzyme activities indicates that heart adenylate cyclase is not located in the sarcoplasmic reticulum but is localized predominantly, if not exclusively, in the plasma membrane."}
{"id": "PMID:188460", "title": "Effects of choleragen on hormonal responsiveness of adenylate cyclase in human fibroblasts and rat fat cells.", "content": "Choleragen increases cyclic AMP content of confluent human fibroblasts. Maximally effective concentrations of isoproterenol and prostaglandin E1 also induce large increases in cyclic AMP content of human fibroblasts and in confluent cultures the effect of prostaglandin E1 is much greater than that of isoproterenol. After incubation with choleragen, the increment in cyclic AMP produced by 2 muM isoproterenol is increased and approaches that produced by5.6 muM prostaglandin E1. Although the concentration of isoproterenol which produces a maximal increase in cyclic AMP is similar in both control and choleragen-treated cells. In choleragen-treated cells, although the response to 5.6 muM prostaglandin E1 is reduced by as much as 50%, the concentration of prostaglandin E1 required to induce a maximal increase in cyclic AMP is 1/10 that required in control cells. Thus the capacities of intact human fibroblasts to respond to isoproterenol and prostaglandin E1 can be altered independently during incubation of intact cells with choleragen. Differences in responsiveness to the two agonists were not demonstrable in adenylate cyclase preparation from control or choleragen-treated cells. In rat fat cells, the effects of choleragen on cyclic AMP content were much smaller than those in fibroblasts. In contrast to its effect on intact fibroblast choleragen treatment of rat fat cells did not alter the accumulation of cyclic AMP in response to a maximally effective concentration of isoproterenol. The responsiveness of adenylate cyclase preparations to isoproterenol was also not altered by exposure of fat cells to choleragen.", "contents": "Effects of choleragen on hormonal responsiveness of adenylate cyclase in human fibroblasts and rat fat cells. Choleragen increases cyclic AMP content of confluent human fibroblasts. Maximally effective concentrations of isoproterenol and prostaglandin E1 also induce large increases in cyclic AMP content of human fibroblasts and in confluent cultures the effect of prostaglandin E1 is much greater than that of isoproterenol. After incubation with choleragen, the increment in cyclic AMP produced by 2 muM isoproterenol is increased and approaches that produced by5.6 muM prostaglandin E1. Although the concentration of isoproterenol which produces a maximal increase in cyclic AMP is similar in both control and choleragen-treated cells. In choleragen-treated cells, although the response to 5.6 muM prostaglandin E1 is reduced by as much as 50%, the concentration of prostaglandin E1 required to induce a maximal increase in cyclic AMP is 1/10 that required in control cells. Thus the capacities of intact human fibroblasts to respond to isoproterenol and prostaglandin E1 can be altered independently during incubation of intact cells with choleragen. Differences in responsiveness to the two agonists were not demonstrable in adenylate cyclase preparation from control or choleragen-treated cells. In rat fat cells, the effects of choleragen on cyclic AMP content were much smaller than those in fibroblasts. In contrast to its effect on intact fibroblast choleragen treatment of rat fat cells did not alter the accumulation of cyclic AMP in response to a maximally effective concentration of isoproterenol. The responsiveness of adenylate cyclase preparations to isoproterenol was also not altered by exposure of fat cells to choleragen."}
{"id": "PMID:188461", "title": "Interaction between glucocorticoids and cyclic AMP in the regulation of phosphoenolpyruvate carboxykinase (GTP) in the isolated perfused rat liver. Effects of cordycepin and cycloheximide.", "content": "The mechanism of the interaction between glucocorticoids and cyclic AMP in the regulation of phosphoenolpyruvate carboxykinase (GTP: oxalocetate carboxylase, transphosphorylating, EC 4.1.1.32) was investigated in the isolated perfused rat liver using inhibitors of transcription or translation. Dibutyryl cyclic AMP produced a rapid increase in P-enolpyruvate carboxykinase activity. The response of the enzyme to the cyclic nucleotide ceased however, at 4 h, but was restored by dexamethasone. The dibutyryl cyclic AMP-induced increase in P-enolpyruvate carboxykinase activity was completely blocked by cycloheximide, but not not by cordycepin. However, cordycepin totalaly suppressed the \"permissive\" effect of dexamethasone on the response of the enzyme to dibutyryl cyclic AMP. Preperfusion of the livers with dexamethasone and cycloheximide, following by perfusion without the steroid hormone and the inhibitor, resulted in a rapid rise in P-enolpyruvate carbosykinase activity, which was not affect by cordycepin. If livers were preperfused with cordycepin for different time-periods, followed by dibutyryl cyclic AMP stimulation of P-enolpyruvate carboxykinase synthesis, the response of the enzyme to the cyclic nucleotide was progressively reduced, achieving 50% inhibition after 1.5 h of preperfusion. These results suggest that the induction of hepatic P-enolpyruvate carboxykinase to maximum values, brought about by cyclic AMP at the level of translation, depends on the supply of newly synthetized mRNA provided by the transcriptional action of glucocorticoids.", "contents": "Interaction between glucocorticoids and cyclic AMP in the regulation of phosphoenolpyruvate carboxykinase (GTP) in the isolated perfused rat liver. Effects of cordycepin and cycloheximide. The mechanism of the interaction between glucocorticoids and cyclic AMP in the regulation of phosphoenolpyruvate carboxykinase (GTP: oxalocetate carboxylase, transphosphorylating, EC 4.1.1.32) was investigated in the isolated perfused rat liver using inhibitors of transcription or translation. Dibutyryl cyclic AMP produced a rapid increase in P-enolpyruvate carboxykinase activity. The response of the enzyme to the cyclic nucleotide ceased however, at 4 h, but was restored by dexamethasone. The dibutyryl cyclic AMP-induced increase in P-enolpyruvate carboxykinase activity was completely blocked by cycloheximide, but not not by cordycepin. However, cordycepin totalaly suppressed the \"permissive\" effect of dexamethasone on the response of the enzyme to dibutyryl cyclic AMP. Preperfusion of the livers with dexamethasone and cycloheximide, following by perfusion without the steroid hormone and the inhibitor, resulted in a rapid rise in P-enolpyruvate carbosykinase activity, which was not affect by cordycepin. If livers were preperfused with cordycepin for different time-periods, followed by dibutyryl cyclic AMP stimulation of P-enolpyruvate carboxykinase synthesis, the response of the enzyme to the cyclic nucleotide was progressively reduced, achieving 50% inhibition after 1.5 h of preperfusion. These results suggest that the induction of hepatic P-enolpyruvate carboxykinase to maximum values, brought about by cyclic AMP at the level of translation, depends on the supply of newly synthetized mRNA provided by the transcriptional action of glucocorticoids."}
{"id": "PMID:188462", "title": "The synthesis of spin-label derivatives of NAD+ and its structural components and their binding to lactate dehydrogenase.", "content": "Spin-labelled derivatives of NAD+ and its structural components (i.e. adenosine, adenine, AMP, ADP and ADPR) have been synthesized. Their binding to pig heart lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) has been studied and dissociation constants have been determined. The spin-labelled derivatives of ADP and ADPR exhibit a tighter binding than the corresponding NAD+ derivative. This may be attributed to the repulsion of the positively charged nicotinamide ring by an histidine side chain in the active center of the enzyme.", "contents": "The synthesis of spin-label derivatives of NAD+ and its structural components and their binding to lactate dehydrogenase. Spin-labelled derivatives of NAD+ and its structural components (i.e. adenosine, adenine, AMP, ADP and ADPR) have been synthesized. Their binding to pig heart lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) has been studied and dissociation constants have been determined. The spin-labelled derivatives of ADP and ADPR exhibit a tighter binding than the corresponding NAD+ derivative. This may be attributed to the repulsion of the positively charged nicotinamide ring by an histidine side chain in the active center of the enzyme."}
{"id": "PMID:188463", "title": "M\u00f6ssbauer and EPR spectroscopy of protocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa.", "content": "Protocatechuate 3,4-dioxygenase (EC 1.13.11.3) from Pseudomonas aeruginosa has been investigated by EPR and M\u00f6ssbauer spectroscopy. Low temperature M\u00f6ssbauer data on the native enzyme (Fe3+, S = 5/2) yields a hyperfine field Hsat=-525 kG at the nucleus. This observation is inconsistent with earlier suggestions, based on EPR data of a rubredoxin-like ligand environment around the iron, i.e. a tetrahedral sulfur coordination. Likewise, the dithionite-reduced enzyme has M\u00f6ssbauer parameters unlike those of reduced rubredoxin. We conclude that the iron atoms are in a previously unrecognized environment. The ternary complex of the enzyme with 3,4-dihydroxyphenylpropionate and O2 yields EPR signals at g = 6.7 and g = 5.3; these signals result from an excited state Kramers doublet. The kinetics of the disappearance of these signals parallels product formation and the decay of the ternary complex as observed in the optical spectrum. The M\u00f6ssbauer and EPR data on the ternary complex establish the iron atoms to be a high-spin ferric state characterized by a large and negative zero-field splitting, D = approximately -2 cm-1.", "contents": "M\u00f6ssbauer and EPR spectroscopy of protocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa. Protocatechuate 3,4-dioxygenase (EC 1.13.11.3) from Pseudomonas aeruginosa has been investigated by EPR and M\u00f6ssbauer spectroscopy. Low temperature M\u00f6ssbauer data on the native enzyme (Fe3+, S = 5/2) yields a hyperfine field Hsat=-525 kG at the nucleus. This observation is inconsistent with earlier suggestions, based on EPR data of a rubredoxin-like ligand environment around the iron, i.e. a tetrahedral sulfur coordination. Likewise, the dithionite-reduced enzyme has M\u00f6ssbauer parameters unlike those of reduced rubredoxin. We conclude that the iron atoms are in a previously unrecognized environment. The ternary complex of the enzyme with 3,4-dihydroxyphenylpropionate and O2 yields EPR signals at g = 6.7 and g = 5.3; these signals result from an excited state Kramers doublet. The kinetics of the disappearance of these signals parallels product formation and the decay of the ternary complex as observed in the optical spectrum. The M\u00f6ssbauer and EPR data on the ternary complex establish the iron atoms to be a high-spin ferric state characterized by a large and negative zero-field splitting, D = approximately -2 cm-1."}
{"id": "PMID:188464", "title": "Purification and immunochemical characterization of aldehyde dehydrogenase from 2-acetylaminofluorene-induced rat hepatomas.", "content": "1. A series of aldehyde dehydrogenase isozymes (aldehyde:NAD (P)+ oxidoreductase, EC 1.2.1.5), has been purified from hepatomas induced in Sprague-Dawley rats by 2-acetylaminofluorene. 2. The functional hepatoma-specific aldehyde dehydrogenase isozymes exist as 105 000-dalton dimers composed to two subunits of 53 000 daltons. Isoelectric points of the purified isozymes are 6.9-7.2. 3. Antiserum to these purified hepatoma-specific aldehyde dehydrogenases has been produced and the immunological relationships of these isozymes to their normal liver counterpart have been studied. Results of Ouchterlony double diffusions, agar-gel immunoelectrophoresis and polyacrylamide gel and agar immunoelectrophoresis indicate that anti-hepatoma aldehyde dehydrogenase antiserum cross-reacts with normal liver aldehyde dehydrogenase.", "contents": "Purification and immunochemical characterization of aldehyde dehydrogenase from 2-acetylaminofluorene-induced rat hepatomas. 1. A series of aldehyde dehydrogenase isozymes (aldehyde:NAD (P)+ oxidoreductase, EC 1.2.1.5), has been purified from hepatomas induced in Sprague-Dawley rats by 2-acetylaminofluorene. 2. The functional hepatoma-specific aldehyde dehydrogenase isozymes exist as 105 000-dalton dimers composed to two subunits of 53 000 daltons. Isoelectric points of the purified isozymes are 6.9-7.2. 3. Antiserum to these purified hepatoma-specific aldehyde dehydrogenases has been produced and the immunological relationships of these isozymes to their normal liver counterpart have been studied. Results of Ouchterlony double diffusions, agar-gel immunoelectrophoresis and polyacrylamide gel and agar immunoelectrophoresis indicate that anti-hepatoma aldehyde dehydrogenase antiserum cross-reacts with normal liver aldehyde dehydrogenase."}
{"id": "PMID:188465", "title": "Deoxythymidine kinase induced in the HELA TK- cells by herpes simplex virus type I and type II. Substrate specificity and kinetic behavior.", "content": "Deoxythymidine kinases (EC 2.7.1.--) induced in HeLa TK- cells by Herpes simplex Type I and Type II viruses both had a requirement for divalent cations. The enzymes had the highest activities in the presence of Mg2+, followed by Mn2+, Ca2+, Fe2+, and in that order, whereas they were inactive in the presence of Zn2+ and Cu2+. The amount of Mg2+ required for optimal activity was dependent on the amount of ATP present, so that optimal activities were found when the concentration of Mg2+ was equal to that of ATP; an excess of Mg2+ inhibited the reaction. The activities of various nucleoside triphosphates as phosphate donors for Herpes simplex virus Type I deoxythymidine kinase were in the order: ATP = dATP = ara ATP greater than CTP greater than dCTP greater than UTP greater than dUTP greater than GTP greater than dGTP. Those for Herpes simplex virus Type II deoxythymidine kinase were in the order: CTP greater than dCTP = ara CTP greater than dATP greater than ATP greater than UTP greater than GTP greater than dUTP = dGTP. For both deoxythymidine kinases induced by Herpes simplex virus, the nucleoside triphosphates tested exerted cooperative effects. The Km values of ATP and CTP for the Herpes simplex virus Type I enzyme were 30 and 70 muM respectively; whereas those for the Herpes simplex virus Typr II enzyme were 140 and 450 muM. Studies on binding of various thymidine analogs with free 5'-OH to these deoxythymidine kinases indicated that 5-substituted ethyl-, vinyl-, allyl-, propyl-, iodo- and bromo-dUrd as well as iodo5 dCyd and bromo5 dCyd had good affinity to both enzymes. In contrast, vinyl5 Urd, iodo5 Urd and arabinosylthymidine had good affinity only to the Herpes simplex virus Type I enzyme but not to the Herpes simplex virus Type II deoxythymidine kinase. All of these thymidine analogs were competitive inhibitors, with KI values in the range of 0.25 to 1.5 muM. Herpes simplex virus Type I deoxythymidine kinase was less sensitive to either dTTP or iodo dUTP inhibition than Herpes simplex virus Type II. Both dThd and dCyd could serve as substrates and competed with each other for Herpes simplex viruses Type I and Type II induced kinases, but they differed in their Km values for these enzymes. The Km values of dThd and dCyd were 0.59 muM and 25 muM for Herpes simplex virus Type I deoxythymidine kinase; while they were 0.36 muM and 88 muM respectively for the Herpes simplex virus Type II enzyme.", "contents": "Deoxythymidine kinase induced in the HELA TK- cells by herpes simplex virus type I and type II. Substrate specificity and kinetic behavior. Deoxythymidine kinases (EC 2.7.1.--) induced in HeLa TK- cells by Herpes simplex Type I and Type II viruses both had a requirement for divalent cations. The enzymes had the highest activities in the presence of Mg2+, followed by Mn2+, Ca2+, Fe2+, and in that order, whereas they were inactive in the presence of Zn2+ and Cu2+. The amount of Mg2+ required for optimal activity was dependent on the amount of ATP present, so that optimal activities were found when the concentration of Mg2+ was equal to that of ATP; an excess of Mg2+ inhibited the reaction. The activities of various nucleoside triphosphates as phosphate donors for Herpes simplex virus Type I deoxythymidine kinase were in the order: ATP = dATP = ara ATP greater than CTP greater than dCTP greater than UTP greater than dUTP greater than GTP greater than dGTP. Those for Herpes simplex virus Type II deoxythymidine kinase were in the order: CTP greater than dCTP = ara CTP greater than dATP greater than ATP greater than UTP greater than GTP greater than dUTP = dGTP. For both deoxythymidine kinases induced by Herpes simplex virus, the nucleoside triphosphates tested exerted cooperative effects. The Km values of ATP and CTP for the Herpes simplex virus Type I enzyme were 30 and 70 muM respectively; whereas those for the Herpes simplex virus Typr II enzyme were 140 and 450 muM. Studies on binding of various thymidine analogs with free 5'-OH to these deoxythymidine kinases indicated that 5-substituted ethyl-, vinyl-, allyl-, propyl-, iodo- and bromo-dUrd as well as iodo5 dCyd and bromo5 dCyd had good affinity to both enzymes. In contrast, vinyl5 Urd, iodo5 Urd and arabinosylthymidine had good affinity only to the Herpes simplex virus Type I enzyme but not to the Herpes simplex virus Type II deoxythymidine kinase. All of these thymidine analogs were competitive inhibitors, with KI values in the range of 0.25 to 1.5 muM. Herpes simplex virus Type I deoxythymidine kinase was less sensitive to either dTTP or iodo dUTP inhibition than Herpes simplex virus Type II. Both dThd and dCyd could serve as substrates and competed with each other for Herpes simplex viruses Type I and Type II induced kinases, but they differed in their Km values for these enzymes. The Km values of dThd and dCyd were 0.59 muM and 25 muM for Herpes simplex virus Type I deoxythymidine kinase; while they were 0.36 muM and 88 muM respectively for the Herpes simplex virus Type II enzyme."}
{"id": "PMID:188466", "title": "Catecholamine-stimulated GTPase activity in turkey erythrocyte membranes.", "content": "Determination of specific GTPase (EC 3.6.1.--) activity in turkey erythrocyte membranes was achieved using low concentration of GTP (0.25 muM), inhibition of nonspecific nucleoside triphosphatases by adenosine 5'(beta,gamma-imino-triphosphate (App(NH)p) and suppression of the transfer of gamma-32P from GTP to ADP with an ATP regeneration system. Under these conditions catacholamines caused a 30--70% increase in GTP hydrolysis. The stimulation of GTPase activity by catecholamines required the presence of Mg2+ or Mn2+. DIfferent batches of membranes revealed the following specific activities (pmol 32Pi/mg protein min): basal GTPase (determined in the absence of catecholamine), 6-- 11; catecholamine-stimulated TTPase, 3--7; and residual non-specific NTPase 3--5. The stimulation of GTPase activity by catecholamines fulfilled the stereospecific requirements of the beta-adrenergic receptor, and was inhibited by propranolol. The concentrations of DL-isoproterenol which half-maximally activated the GTPase and adenylate cyclase were 1 and 1.2 muM, respectively. The following findings indicate that the catecholamine-stimulated GTPase is independent of the catalytic production of cyclic AMP by the adenylate cyclase. Addition of cyclic AMP to the GTPase assay did not change the rate of GTP hydrolysis. Furthermore, treatment of the membrane with N-ethylmaleimide (MalNEt) at 0 degrees C which caused 98% inhibition of the adenylate cyclase, had no effect on the catecholamine-stimulated GTPase. The affinity and specificity for GTP in the GTPase reactions are similar to those previously reported for the stimulation of the adenylate cyclase. The apparent Km for GTP in the basal and the catecholamine-stimulated GTPase reaction was 0.1 muM. These GTPase activities were inhibited by ITP but not by CTP and UTP. It is proposed that a catecholamine-stimulated GTPase is a component of the turkey erythrocyte adenylate cyclase system.", "contents": "Catecholamine-stimulated GTPase activity in turkey erythrocyte membranes. Determination of specific GTPase (EC 3.6.1.--) activity in turkey erythrocyte membranes was achieved using low concentration of GTP (0.25 muM), inhibition of nonspecific nucleoside triphosphatases by adenosine 5'(beta,gamma-imino-triphosphate (App(NH)p) and suppression of the transfer of gamma-32P from GTP to ADP with an ATP regeneration system. Under these conditions catacholamines caused a 30--70% increase in GTP hydrolysis. The stimulation of GTPase activity by catecholamines required the presence of Mg2+ or Mn2+. DIfferent batches of membranes revealed the following specific activities (pmol 32Pi/mg protein min): basal GTPase (determined in the absence of catecholamine), 6-- 11; catecholamine-stimulated TTPase, 3--7; and residual non-specific NTPase 3--5. The stimulation of GTPase activity by catecholamines fulfilled the stereospecific requirements of the beta-adrenergic receptor, and was inhibited by propranolol. The concentrations of DL-isoproterenol which half-maximally activated the GTPase and adenylate cyclase were 1 and 1.2 muM, respectively. The following findings indicate that the catecholamine-stimulated GTPase is independent of the catalytic production of cyclic AMP by the adenylate cyclase. Addition of cyclic AMP to the GTPase assay did not change the rate of GTP hydrolysis. Furthermore, treatment of the membrane with N-ethylmaleimide (MalNEt) at 0 degrees C which caused 98% inhibition of the adenylate cyclase, had no effect on the catecholamine-stimulated GTPase. The affinity and specificity for GTP in the GTPase reactions are similar to those previously reported for the stimulation of the adenylate cyclase. The apparent Km for GTP in the basal and the catecholamine-stimulated GTPase reaction was 0.1 muM. These GTPase activities were inhibited by ITP but not by CTP and UTP. It is proposed that a catecholamine-stimulated GTPase is a component of the turkey erythrocyte adenylate cyclase system."}
{"id": "PMID:188467", "title": "Guanosine monophosphate synthetase from Ehrlich ascites cells. Multiple inhibition by pyrophosphate and nucleosides.", "content": "GMP synthetase (xanthosine-5'-phosphate: ammonia ligase (AMP-forming), EC 6.3.4.1) from Ehrlich ascites cells was found to be subject to multiple inhibition by its reaction product, PPi, and some analogs of adenosine. PPi and the nucleoside (N) inhibitors were also capable of individually inhibiting this enzyme. Under no conditions did the inhibition appear to be irreversible or \"pseudoinactivating\" in nature. The individual inhibition by PPi was competitive with respect to ATP (KI = 0.42 mM). Conversely, in the absence of PPi, the binding of N was noncompetitive with ATP, but shifted to a competitive pattern when PPi was present. Furthermore, with the inhibitors in concert, there was an apparent lowering of the KI values for both inhibitors. This data was consistent with either PPi functioning to tighten the binding of N at a noncatalytic site (positive cooperativity) or with PPi actually opening a second binding site for N in addition to the non-catalytic site. Although this study did not distinguish which of these events was occurring, it did reveal that the intensity of the effect of PPi appeared to be constant. That is, for various N inhibitors with a range of independently determined KI values from 26 to 1650 muM, the ratio of their KI values determined in the absence of PPi to the values determined in the presence of PPi was always 38 +/- 1.", "contents": "Guanosine monophosphate synthetase from Ehrlich ascites cells. Multiple inhibition by pyrophosphate and nucleosides. GMP synthetase (xanthosine-5'-phosphate: ammonia ligase (AMP-forming), EC 6.3.4.1) from Ehrlich ascites cells was found to be subject to multiple inhibition by its reaction product, PPi, and some analogs of adenosine. PPi and the nucleoside (N) inhibitors were also capable of individually inhibiting this enzyme. Under no conditions did the inhibition appear to be irreversible or \"pseudoinactivating\" in nature. The individual inhibition by PPi was competitive with respect to ATP (KI = 0.42 mM). Conversely, in the absence of PPi, the binding of N was noncompetitive with ATP, but shifted to a competitive pattern when PPi was present. Furthermore, with the inhibitors in concert, there was an apparent lowering of the KI values for both inhibitors. This data was consistent with either PPi functioning to tighten the binding of N at a noncatalytic site (positive cooperativity) or with PPi actually opening a second binding site for N in addition to the non-catalytic site. Although this study did not distinguish which of these events was occurring, it did reveal that the intensity of the effect of PPi appeared to be constant. That is, for various N inhibitors with a range of independently determined KI values from 26 to 1650 muM, the ratio of their KI values determined in the absence of PPi to the values determined in the presence of PPi was always 38 +/- 1."}
{"id": "PMID:188468", "title": "Solubilization and photoaffinity labeling of renal membrane cyclic AMP receptors.", "content": "Renal cortical plasma membranes were solubilized with sodium deoxycholate. The membrane-bound cyclic AMP  receptors retained biologic activity in the detergent-dispersed state exhibiting the properties of high affinity for cyclic AMP, saturability and specificity. Half-maximal binding of cycle [3H]-AMP to these receptors was found to occur at 0.06 muM and 1.5 pmol of cyclic [3H]AMP was bound per mg membrane protein at saturation (0.5 muM cyclic [3H]AMP). Sodium deoxycholate-solubilized membrane proteins were chromatographed on Biogel A-5m. Cyclic [3H]AMP receptors  eluted in the internal volume at positions equivalent to molecular sizes of 50 000 and 20 000 daltons and in the void volume at molecular size greater than 450 000. After photoaffinity labeling the renal membrane receptors with cyclic [3H]AMP, we found peaks of tritium radioactivity which eluted at similar molecular size positions on this Bogel A-5m column. Further treatment of photoaffinity labeled membranes with sodium dodecyl sulfate, mercaptoethanol and urea, followed by polyacrylamide gel electrophoresis, showed bands of tritium-labeled receptor protein with relative mobilities corresponding to molecular sizes of 26 000 and 21 000 daltons. This study shows that porcine renal cortical membranes contain at least two molecular species of cyclic AMP receptors which may be associated with regulation of the membrane-bound cyclic AMP-dependent protein kinase.", "contents": "Solubilization and photoaffinity labeling of renal membrane cyclic AMP receptors. Renal cortical plasma membranes were solubilized with sodium deoxycholate. The membrane-bound cyclic AMP  receptors retained biologic activity in the detergent-dispersed state exhibiting the properties of high affinity for cyclic AMP, saturability and specificity. Half-maximal binding of cycle [3H]-AMP to these receptors was found to occur at 0.06 muM and 1.5 pmol of cyclic [3H]AMP was bound per mg membrane protein at saturation (0.5 muM cyclic [3H]AMP). Sodium deoxycholate-solubilized membrane proteins were chromatographed on Biogel A-5m. Cyclic [3H]AMP receptors  eluted in the internal volume at positions equivalent to molecular sizes of 50 000 and 20 000 daltons and in the void volume at molecular size greater than 450 000. After photoaffinity labeling the renal membrane receptors with cyclic [3H]AMP, we found peaks of tritium radioactivity which eluted at similar molecular size positions on this Bogel A-5m column. Further treatment of photoaffinity labeled membranes with sodium dodecyl sulfate, mercaptoethanol and urea, followed by polyacrylamide gel electrophoresis, showed bands of tritium-labeled receptor protein with relative mobilities corresponding to molecular sizes of 26 000 and 21 000 daltons. This study shows that porcine renal cortical membranes contain at least two molecular species of cyclic AMP receptors which may be associated with regulation of the membrane-bound cyclic AMP-dependent protein kinase."}
{"id": "PMID:188469", "title": "Effects of common inhibitors of gastric acid secretion on secretagogue-induced respiration and aminopyrine accumulation in isolated gastric glands.", "content": "1. The effects of three inhibitors of gastric acid secretion, atropine, burimamide and thiocyanate, have been studied in isolated glands from the rabbit gastric mucosa. The glands were either resting or stimulated by carbachol, histamine or dibutyryl cyclic AMP. The effects were determined from changes in oxygen consumption and accumulation of the weak base aminopyrine. The latter gives an indirect measurement of the acid production in the glands. 2. Atropine (10 (-6) M) almost totally inhibited the transient response induced by carbachol (10 (-4) M) in both measured parameters. The histamine-induced increase in respiration was inhibited when the atropine concentration was raised to 10 (-4) M. To a lesser extent also, histamine-induced aminopyrine accumulation was reduced. The dibutyryl cyclic AMP stimulated oxygen consumption was not affected by atropine. 3. Burimamide competitively inhibited the histamine responses but was without effect on those of carbachol and dibutyryl cyclic AMP. 4. Thiocyanate (10 (-2) M) inhibited the increase in oxygen consumption induced by all three secretagogues but not down the prestimulatory level, in spite of total abolishment of the aminopyrine accumulation. 5. In unstimulated glands, burimamide (10 (-3) M) or atropine (10 (-4) M) did not alter the normal aminopyrine ratio (aminopyrine in intraglandular water/ aminopyrine in extraglandular water) of approximately 50. This may indicate the existence of preformed acid in resting parietal cells. Thiocyanate, on the other hand, lowered the aminopyrine ratio in unstimulated glands from 46 to 2. Possible mechanisms for the thiocyanate effect are discussed in terms of an inability to separate acid and base in the secreting membrane.", "contents": "Effects of common inhibitors of gastric acid secretion on secretagogue-induced respiration and aminopyrine accumulation in isolated gastric glands. 1. The effects of three inhibitors of gastric acid secretion, atropine, burimamide and thiocyanate, have been studied in isolated glands from the rabbit gastric mucosa. The glands were either resting or stimulated by carbachol, histamine or dibutyryl cyclic AMP. The effects were determined from changes in oxygen consumption and accumulation of the weak base aminopyrine. The latter gives an indirect measurement of the acid production in the glands. 2. Atropine (10 (-6) M) almost totally inhibited the transient response induced by carbachol (10 (-4) M) in both measured parameters. The histamine-induced increase in respiration was inhibited when the atropine concentration was raised to 10 (-4) M. To a lesser extent also, histamine-induced aminopyrine accumulation was reduced. The dibutyryl cyclic AMP stimulated oxygen consumption was not affected by atropine. 3. Burimamide competitively inhibited the histamine responses but was without effect on those of carbachol and dibutyryl cyclic AMP. 4. Thiocyanate (10 (-2) M) inhibited the increase in oxygen consumption induced by all three secretagogues but not down the prestimulatory level, in spite of total abolishment of the aminopyrine accumulation. 5. In unstimulated glands, burimamide (10 (-3) M) or atropine (10 (-4) M) did not alter the normal aminopyrine ratio (aminopyrine in intraglandular water/ aminopyrine in extraglandular water) of approximately 50. This may indicate the existence of preformed acid in resting parietal cells. Thiocyanate, on the other hand, lowered the aminopyrine ratio in unstimulated glands from 46 to 2. Possible mechanisms for the thiocyanate effect are discussed in terms of an inability to separate acid and base in the secreting membrane."}
{"id": "PMID:188470", "title": "The structure of vesicular stomatitis virus membrane. A phosphorus nuclear magnetic resonance approach.", "content": "The proton decoupled 40.48 M Hz 31P NMR spectrum of intact and unperturbed membrane-enclosed vesicular stomatitis virus (sterotype Indiana) exhibited two distinct maxima. These can be resolved into a narrow, symmetric line and a broad asymmetric line. The 31P NMR spectrum of a multilamellar (unsonicated) preparation of the extracted viral lipids exhibited a line shape similar to that of the intact virus. A sonicated vesicle preparation of the extracted viral lipids exhibited a narrow symmetric line. The narrow component in the intact virus spectrum may be attributed to small membrane fragments. Phospholipase C digestion of the intact virus resulted in substantial reduction in intensity of both components which suggests that much of the contribution to both peaks is due to phosphate in the phospholipid polar head groups. The phospholipid phosphates in both sonicated and unsonicated preparations of the extracted viral lipids exhibited substantially longer relaxation times than did those in the intact virus. The short relaxation time emanating from the intact virus preparation is caused by immobilization of the phospholipid head groups which could be due to lipid-protein interactions. Trypsin treatment of vesicular stomatitis virions, which results in complete removal of the exterior hydrophilic segment of the membrane glycoprotein, increased the 31P relaxation time to a value similar to that observed in the protein-free total lipid extracts; this finding provides supporting evidence for the role of virus glycoprotein in shortened relaxation times. A reversible temperature-dependent change in apparent line width and absence of an effect of cholesterol on the 31P phospholipid spectrum were also demonstrated.", "contents": "The structure of vesicular stomatitis virus membrane. A phosphorus nuclear magnetic resonance approach. The proton decoupled 40.48 M Hz 31P NMR spectrum of intact and unperturbed membrane-enclosed vesicular stomatitis virus (sterotype Indiana) exhibited two distinct maxima. These can be resolved into a narrow, symmetric line and a broad asymmetric line. The 31P NMR spectrum of a multilamellar (unsonicated) preparation of the extracted viral lipids exhibited a line shape similar to that of the intact virus. A sonicated vesicle preparation of the extracted viral lipids exhibited a narrow symmetric line. The narrow component in the intact virus spectrum may be attributed to small membrane fragments. Phospholipase C digestion of the intact virus resulted in substantial reduction in intensity of both components which suggests that much of the contribution to both peaks is due to phosphate in the phospholipid polar head groups. The phospholipid phosphates in both sonicated and unsonicated preparations of the extracted viral lipids exhibited substantially longer relaxation times than did those in the intact virus. The short relaxation time emanating from the intact virus preparation is caused by immobilization of the phospholipid head groups which could be due to lipid-protein interactions. Trypsin treatment of vesicular stomatitis virions, which results in complete removal of the exterior hydrophilic segment of the membrane glycoprotein, increased the 31P relaxation time to a value similar to that observed in the protein-free total lipid extracts; this finding provides supporting evidence for the role of virus glycoprotein in shortened relaxation times. A reversible temperature-dependent change in apparent line width and absence of an effect of cholesterol on the 31P phospholipid spectrum were also demonstrated."}
{"id": "PMID:188471", "title": "Catechol, a structural requirement for (Na+ + K+)-ATPase stimulation in rat skeletal muscle membrane.", "content": "1. Catecholamines can nearly double (Na+ + K+)-ATPase acts effect is not mediated by cyclic AMP and is not beta-adrenergic. 3. Orthodihydroxybenzene compounds and their orthoquinone derivatives enhance (Na+ + K+)-ATPase activity. 4. Enhancement of (Na+ + K+)-ATPase activity by catechols is not due to increased availability of ATP. 5. It is suggested that catechols and their orthoquinones somehow alter or protect the configuration of the enzyme so that it becomes more active or so protect the configuration of the enzyme so that it becomes more active or so that its activity is maintained under conditions in which its activity is otherwise diminished.", "contents": "Catechol, a structural requirement for (Na+ + K+)-ATPase stimulation in rat skeletal muscle membrane. 1. Catecholamines can nearly double (Na+ + K+)-ATPase acts effect is not mediated by cyclic AMP and is not beta-adrenergic. 3. Orthodihydroxybenzene compounds and their orthoquinone derivatives enhance (Na+ + K+)-ATPase activity. 4. Enhancement of (Na+ + K+)-ATPase activity by catechols is not due to increased availability of ATP. 5. It is suggested that catechols and their orthoquinones somehow alter or protect the configuration of the enzyme so that it becomes more active or so protect the configuration of the enzyme so that it becomes more active or so that its activity is maintained under conditions in which its activity is otherwise diminished."}
{"id": "PMID:188472", "title": "beta-Adrenergic effect on Na+-K+ transport in rat skeletal muscle.", "content": "1. Intact rat extensor digitorum longus muscles soaked in L-isoproterenol plus 10(-5) M ouabain gained less sarcoplasmic Na+ than did muscles soaked in ouabain alone. Half maximal effect was produced by 10(-8) M L-isoproterenol. 2. D-Isoproterenol and oxidized L-isoproterenol were only 3 and 1%, respectively, as potent as L-isoproterenol. Other catechols tested had no effect. 3. The effect of L-isoproterenol on sarcoplasmic Na+ content appears to be a beta-adrenergic function in that it was blocked by propranolol, but not by phentolamine, and could be mimicked by dibutyryl cyclic AMP or by caffeine. 4. Reduced gain in sarcoplasmic Na+ was accompanied by reduced loss of sarcoplasmic K+. 5. L-Isoproterenol increased loss of sarcoplasmic Na+ in the absence of ouabain, in muscles recovering from cold treatment. 6. Results suggest that the beta-adrenergic system stimulates a coupled Na-K+ pump. 7. A model is proposed in which stimulation of the Na+-K+ pump in response to beta-adrenergic agents involves a number of intermediate steps, identified tentatively.", "contents": "beta-Adrenergic effect on Na+-K+ transport in rat skeletal muscle. 1. Intact rat extensor digitorum longus muscles soaked in L-isoproterenol plus 10(-5) M ouabain gained less sarcoplasmic Na+ than did muscles soaked in ouabain alone. Half maximal effect was produced by 10(-8) M L-isoproterenol. 2. D-Isoproterenol and oxidized L-isoproterenol were only 3 and 1%, respectively, as potent as L-isoproterenol. Other catechols tested had no effect. 3. The effect of L-isoproterenol on sarcoplasmic Na+ content appears to be a beta-adrenergic function in that it was blocked by propranolol, but not by phentolamine, and could be mimicked by dibutyryl cyclic AMP or by caffeine. 4. Reduced gain in sarcoplasmic Na+ was accompanied by reduced loss of sarcoplasmic K+. 5. L-Isoproterenol increased loss of sarcoplasmic Na+ in the absence of ouabain, in muscles recovering from cold treatment. 6. Results suggest that the beta-adrenergic system stimulates a coupled Na-K+ pump. 7. A model is proposed in which stimulation of the Na+-K+ pump in response to beta-adrenergic agents involves a number of intermediate steps, identified tentatively."}
{"id": "PMID:188473", "title": "A spin label study of lipid oxidation catalyzed by heme proteins.", "content": "Rapid loss of the electron spin resonance signal from a variety of spin labels is observed when ferricytochrome c or metmyoglobin are combined with lipids. Evidence is presented that this loss of signal can be used as a sensitive method to study lipid oxidation catalyzed by heme proteins. Under aerobic conditions and with lipids which bind the heme protein, the kinetics of the oxidation process as observed by the spin label method are identical to the kinetics previously observed by measurements of oxygen uptake. Use of pre-oxidized lipids under anaerobic conditions indicates that cytochrome c reacts with a product of lipid oxidation. Kinetic studies of the anaerobic reaction indicate that cytochrome c reacts rapidly with lipid oxidation products in membrane areas far larger than the area occupied by cytochrome c, implying rapid transport of reactive species within the membrane interior in directions parallel to the membrane surface. Under anaerobic conditions, reaction of cytochrome c with lipid oxidation products appears to produce a relatively long lived (hours) species located in the hydrophobic portion of the membrane, which is capable of subsequent reaction with lipid-soluble spin labels.", "contents": "A spin label study of lipid oxidation catalyzed by heme proteins. Rapid loss of the electron spin resonance signal from a variety of spin labels is observed when ferricytochrome c or metmyoglobin are combined with lipids. Evidence is presented that this loss of signal can be used as a sensitive method to study lipid oxidation catalyzed by heme proteins. Under aerobic conditions and with lipids which bind the heme protein, the kinetics of the oxidation process as observed by the spin label method are identical to the kinetics previously observed by measurements of oxygen uptake. Use of pre-oxidized lipids under anaerobic conditions indicates that cytochrome c reacts with a product of lipid oxidation. Kinetic studies of the anaerobic reaction indicate that cytochrome c reacts rapidly with lipid oxidation products in membrane areas far larger than the area occupied by cytochrome c, implying rapid transport of reactive species within the membrane interior in directions parallel to the membrane surface. Under anaerobic conditions, reaction of cytochrome c with lipid oxidation products appears to produce a relatively long lived (hours) species located in the hydrophobic portion of the membrane, which is capable of subsequent reaction with lipid-soluble spin labels."}
{"id": "PMID:188474", "title": "Location of two sulfhydryl groups in the rhodopsin molecule by use of the spin label technique.", "content": "Sulfhydryl groups of membrane-bound rhodopsin are studied with the spin label technique by using five maleimide derivative probes of different lengths. Two sulfhydryl groups are titrated per molecule of rhodopsin, These groups are located in protected but probably different environments, less than 12 A away from the aqueous phase. A distance of about 37 A is measured between the two groups. These results are consistent with a model in which the two groups would be located close by the external surface of the protein but embedded within the membrane layer, the strong immobilization of the label molecules resulting from phosphlipid-protein interactions.", "contents": "Location of two sulfhydryl groups in the rhodopsin molecule by use of the spin label technique. Sulfhydryl groups of membrane-bound rhodopsin are studied with the spin label technique by using five maleimide derivative probes of different lengths. Two sulfhydryl groups are titrated per molecule of rhodopsin, These groups are located in protected but probably different environments, less than 12 A away from the aqueous phase. A distance of about 37 A is measured between the two groups. These results are consistent with a model in which the two groups would be located close by the external surface of the protein but embedded within the membrane layer, the strong immobilization of the label molecules resulting from phosphlipid-protein interactions."}
{"id": "PMID:188475", "title": "Electron spin resonance studies of the membranes of the cellular slime mold Dictyostelium discoideum.", "content": "Doxylstearic acid spin labels are used to study the fluidity of the membranes of the cellular slime mold, Dictyostelium discoideum. The tau omicron value of the wild-type cell membrane is close to that of egg lecithin indicating a rather fluid membrane. No detectable change in the fluidity of the bulk lipids at the 16-carbon depth occurs during differentiation of the myxamoebae into stalk and spore cells despite reported changes in the individual lipid components. The results of studies on temperature-sensitive and aggregationless mutants are also presented.", "contents": "Electron spin resonance studies of the membranes of the cellular slime mold Dictyostelium discoideum. Doxylstearic acid spin labels are used to study the fluidity of the membranes of the cellular slime mold, Dictyostelium discoideum. The tau omicron value of the wild-type cell membrane is close to that of egg lecithin indicating a rather fluid membrane. No detectable change in the fluidity of the bulk lipids at the 16-carbon depth occurs during differentiation of the myxamoebae into stalk and spore cells despite reported changes in the individual lipid components. The results of studies on temperature-sensitive and aggregationless mutants are also presented."}
{"id": "PMID:188476", "title": "Studies on the iodinated surface membrane proteins and concanavalin A agglutination of transformed Syrian hamster cells.", "content": "Chemically transformed Syrian hamster cells exhibit marked agglutination in the presence of the plant lectin, concanavalin A. In this report, we describe conditions which can alter this concanavalin A agglutinability, and compare the surface proteins from transformed cells which express different degrees of agglutinability. Lactoperoxidase-catalyzed iodination of tertiary Syrian hamster cells reveals the major iodinatable protein to be approximately 220 000 daltons. The transformed Syrian hamster cells do not contain this protein in an iodinatable form. Analyses of the transformed cells grown under conditions which decrease the concanavalin A agglutinability do not demonstrate any iodination of the 220 000 mol. wt. protein. These results depict the effects of growth and dibutyryl cyclic AMP on the iodinatable cell surface proteins of transformed cells and indicate that the absence of the I-220 000 mol. wt. protein is probably not a major determinant of concanavalin A agglutination.", "contents": "Studies on the iodinated surface membrane proteins and concanavalin A agglutination of transformed Syrian hamster cells. Chemically transformed Syrian hamster cells exhibit marked agglutination in the presence of the plant lectin, concanavalin A. In this report, we describe conditions which can alter this concanavalin A agglutinability, and compare the surface proteins from transformed cells which express different degrees of agglutinability. Lactoperoxidase-catalyzed iodination of tertiary Syrian hamster cells reveals the major iodinatable protein to be approximately 220 000 daltons. The transformed Syrian hamster cells do not contain this protein in an iodinatable form. Analyses of the transformed cells grown under conditions which decrease the concanavalin A agglutinability do not demonstrate any iodination of the 220 000 mol. wt. protein. These results depict the effects of growth and dibutyryl cyclic AMP on the iodinatable cell surface proteins of transformed cells and indicate that the absence of the I-220 000 mol. wt. protein is probably not a major determinant of concanavalin A agglutination."}
{"id": "PMID:188477", "title": "Divergent effects of cyanate on amino acid and phosphate uptake by liver and hepatoma.", "content": "The uptake of alpha-aminoiso[3H]butyric acid and 32Pi was observed to be inhibited by sodium cyanate in transplanted hepatomas but was increased in the livers of the tumor bearing rats. Incorporation of 32Pi into macromolecules in hepatomas was also inhibited by cyanate. Treatment with this drug did not influence circulating concentrations of isotope-labeled materials. There were relatively small effects on uptake of 36Cl- in cyanate-treated rats and the action was not tissue specific. The data were compatible with an inhibitory effect of cyanate on active transport in hepatomas which was not seen under the same conditions in host liver.", "contents": "Divergent effects of cyanate on amino acid and phosphate uptake by liver and hepatoma. The uptake of alpha-aminoiso[3H]butyric acid and 32Pi was observed to be inhibited by sodium cyanate in transplanted hepatomas but was increased in the livers of the tumor bearing rats. Incorporation of 32Pi into macromolecules in hepatomas was also inhibited by cyanate. Treatment with this drug did not influence circulating concentrations of isotope-labeled materials. There were relatively small effects on uptake of 36Cl- in cyanate-treated rats and the action was not tissue specific. The data were compatible with an inhibitory effect of cyanate on active transport in hepatomas which was not seen under the same conditions in host liver."}
{"id": "PMID:188478", "title": "Thermal elution chromatography of nucleic acids on hydroxyapatite.", "content": "Hydroxyapatite thermal elution chromatography was studied from an empirical standpoint. The dependence of elution temperature on elution buffer concentration was determined for various types of buffer, hydroxyapatite and nucleic acid. The results are analyzed in terms of the proper design and interpretation of thermal elution experiments. The potential for serious artifacts is demonstrated and the means by which they may be avoided is described. Various commercially available hydroxyapatites were tested in conjunction with various aqueous and partially non-aqueous buffer systems. Among the materials tested, potassium phosphate and Bio-Rad HTP were found to constitute the best buffer-hydroxyapatite system for most types of thermal elution study.", "contents": "Thermal elution chromatography of nucleic acids on hydroxyapatite. Hydroxyapatite thermal elution chromatography was studied from an empirical standpoint. The dependence of elution temperature on elution buffer concentration was determined for various types of buffer, hydroxyapatite and nucleic acid. The results are analyzed in terms of the proper design and interpretation of thermal elution experiments. The potential for serious artifacts is demonstrated and the means by which they may be avoided is described. Various commercially available hydroxyapatites were tested in conjunction with various aqueous and partially non-aqueous buffer systems. Among the materials tested, potassium phosphate and Bio-Rad HTP were found to constitute the best buffer-hydroxyapatite system for most types of thermal elution study."}
{"id": "PMID:188479", "title": "Properties of the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart.", "content": "In the absence of activator, the activator-dependent cyclic nucleotide phosphodiesterase (EC 3.1.4.-) from bovine heart hydrolyzed 3.2-fold more cyclic GMP than cyclic AMP when assayed with 10(-6) M substrate in the presence of 5 mM Mg2+ and 10 muM Ca2+. The addition of saturating amounts of phosphodiesterase activator increased the hydrolysis of cyclic GMP 8-fold and cyclic AMP 6-fold. The pH maxima of the enzyme was rather broad from 6.0 to 7.0 for the hydrolysis of both cyclic GMP and cyclic AMP in the absnece or presence of phosphodiesterase activator. Substrate specificity of the enzyme in the absence or presence of phosphodiesterase activator varied depending on the divalent metal used to support activity in the absence of activator. The enzyme preferentially hydrolyzed cyclic GMP in the presence of Mg2+ while little substrate specificity was observed in the presence of Mn2+, Zn2+, Co2+ or Ni2+. The magnitude of the increase in enzyme activity due to activator and Ca2+ varied depending on the divalent metal used to support enzyme activity without activator. The addition of activator increased the V of cyclic AMP hydrolysis 1.7-fold while causing no significant change in the Km for cyclic AMP. Two apparent Km values for cyclic GMP (1 and 15 muM) were noted in the absence of activator and upon the addition of activator a single apparent Km (3 muM) was observed with a V approx. 2-fold above that in the absence of activator. Cyclic AMP competitively inhibitied the hydrolysis of cyclic GMP with a ki of 50 muM while cyclic GMP non-competitively inhibited the hydrolysis of cyclic AMP with a Ki of 1.8 muM. The results suggest there may be two or more binding sites for cyclic GMP on the enzyme and possibly only one binding site for cyclic AMP.", "contents": "Properties of the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart. In the absence of activator, the activator-dependent cyclic nucleotide phosphodiesterase (EC 3.1.4.-) from bovine heart hydrolyzed 3.2-fold more cyclic GMP than cyclic AMP when assayed with 10(-6) M substrate in the presence of 5 mM Mg2+ and 10 muM Ca2+. The addition of saturating amounts of phosphodiesterase activator increased the hydrolysis of cyclic GMP 8-fold and cyclic AMP 6-fold. The pH maxima of the enzyme was rather broad from 6.0 to 7.0 for the hydrolysis of both cyclic GMP and cyclic AMP in the absnece or presence of phosphodiesterase activator. Substrate specificity of the enzyme in the absence or presence of phosphodiesterase activator varied depending on the divalent metal used to support activity in the absence of activator. The enzyme preferentially hydrolyzed cyclic GMP in the presence of Mg2+ while little substrate specificity was observed in the presence of Mn2+, Zn2+, Co2+ or Ni2+. The magnitude of the increase in enzyme activity due to activator and Ca2+ varied depending on the divalent metal used to support enzyme activity without activator. The addition of activator increased the V of cyclic AMP hydrolysis 1.7-fold while causing no significant change in the Km for cyclic AMP. Two apparent Km values for cyclic GMP (1 and 15 muM) were noted in the absence of activator and upon the addition of activator a single apparent Km (3 muM) was observed with a V approx. 2-fold above that in the absence of activator. Cyclic AMP competitively inhibitied the hydrolysis of cyclic GMP with a ki of 50 muM while cyclic GMP non-competitively inhibited the hydrolysis of cyclic AMP with a Ki of 1.8 muM. The results suggest there may be two or more binding sites for cyclic GMP on the enzyme and possibly only one binding site for cyclic AMP."}
{"id": "PMID:188480", "title": "Structural and kinetic studies on the activators of succinate dehydrogenase.", "content": "1. Diverse classes of compounds such as dicarboxylates, pyrophosphates, quinols and nitrophenols are known to activate mitochondrial succinate dehydrogenase (EC 1.3.99.1). Examples in each class -- malonate, pyrophosphate, ubiquinol and 2,4-dinitrophenol -- are selected for comparative studies on the kinetic constants and structural relationship. 2. The activated forms of the enzyme obtained on preincubating mitochondria with the effectors exhibited Michaelian kinetics and gave double-reciprocal plots which are nearly parallel to that of the basal form. On activation, Km for the substrate also increased along with V. The effectors activated the enzyme at low concentrations and inhibited, in a competitive fashion, at high concentrations. The binding constant for activation was lower than that for inhibition for each effector. 3. These compounds possess ionizable twin oxygens separated by a distance of 5.5 +/- 0.8 A and having fractional charges in the range of -0.26 to -0.74 e. The common twin-oxygen feature of the substrate and the effectors suggested the presence of corresponding counter charges in the binding domain. The competitive nature of effectors with the substrate for inhibition further indicated the close structural resemblance of the activation and catalytic sites.", "contents": "Structural and kinetic studies on the activators of succinate dehydrogenase. 1. Diverse classes of compounds such as dicarboxylates, pyrophosphates, quinols and nitrophenols are known to activate mitochondrial succinate dehydrogenase (EC 1.3.99.1). Examples in each class -- malonate, pyrophosphate, ubiquinol and 2,4-dinitrophenol -- are selected for comparative studies on the kinetic constants and structural relationship. 2. The activated forms of the enzyme obtained on preincubating mitochondria with the effectors exhibited Michaelian kinetics and gave double-reciprocal plots which are nearly parallel to that of the basal form. On activation, Km for the substrate also increased along with V. The effectors activated the enzyme at low concentrations and inhibited, in a competitive fashion, at high concentrations. The binding constant for activation was lower than that for inhibition for each effector. 3. These compounds possess ionizable twin oxygens separated by a distance of 5.5 +/- 0.8 A and having fractional charges in the range of -0.26 to -0.74 e. The common twin-oxygen feature of the substrate and the effectors suggested the presence of corresponding counter charges in the binding domain. The competitive nature of effectors with the substrate for inhibition further indicated the close structural resemblance of the activation and catalytic sites."}
{"id": "PMID:188481", "title": "Spectrophotometric studies on NAD(P)H oxidase of leukocytes. 1. The relationship between granule-NAD(P)H oxidase and myeloperoxidase.", "content": "The NAD(P)H oxidase located in granules from resting leukocytes seems to be identical with myeloperoxidase on the basis of the following results. Spectral changes representing the difference between granules with and without NAD(P)H under various conditions represented the formation of compound III of myeloperoxidase, corresponding to the oxidation of NAD(P)H. The KCN difference spectrum of granules from both resting and phagocytizing leukocytes was in agreement with the KCN difference spectrum of myeloperoxidase. The affinity of KCN for myeloperoxidase was the same in both resting and phagocytizing leukocytes. The KCN-sensitive portion of NAD(P)H oxidase of granules from phagocytizing leukocytes seems to be identical with isolated myeloperoxidase and the myeloperoxidase of resting leukocytes. The KCN-insensitive oxidation of NAD(P)H by granules from phagocytizing leukocytes has not been found to be identical with myeloperoxidase.", "contents": "Spectrophotometric studies on NAD(P)H oxidase of leukocytes. 1. The relationship between granule-NAD(P)H oxidase and myeloperoxidase. The NAD(P)H oxidase located in granules from resting leukocytes seems to be identical with myeloperoxidase on the basis of the following results. Spectral changes representing the difference between granules with and without NAD(P)H under various conditions represented the formation of compound III of myeloperoxidase, corresponding to the oxidation of NAD(P)H. The KCN difference spectrum of granules from both resting and phagocytizing leukocytes was in agreement with the KCN difference spectrum of myeloperoxidase. The affinity of KCN for myeloperoxidase was the same in both resting and phagocytizing leukocytes. The KCN-sensitive portion of NAD(P)H oxidase of granules from phagocytizing leukocytes seems to be identical with isolated myeloperoxidase and the myeloperoxidase of resting leukocytes. The KCN-insensitive oxidation of NAD(P)H by granules from phagocytizing leukocytes has not been found to be identical with myeloperoxidase."}
{"id": "PMID:188482", "title": "The binding of [3H]dolichol by plasma high density lipoproteins.", "content": "Radioactive dolichol was rapidly taken up by a plasma protein fraction following the intravenous injection of detergent suspended [3H]dolichol into rats. The half-life of labeled dolichol in the plasma was found to be approx. 13 h. Density gradient centrifugation or gel filtration of samples of human or rat plasma incubated with [3H]dolichol suspensions also showed that the labeled material became associated with the same plasma protein fractions as in the in vivo studies. Evidence was obtained to indicate that dolichol is specifically associated with the high density lipoprotein fraction of plasma. The possible role of high density lipoproteins as a vehicle for dolichol transport and the problems involved in the binding of this long moleculare are discussed.", "contents": "The binding of [3H]dolichol by plasma high density lipoproteins. Radioactive dolichol was rapidly taken up by a plasma protein fraction following the intravenous injection of detergent suspended [3H]dolichol into rats. The half-life of labeled dolichol in the plasma was found to be approx. 13 h. Density gradient centrifugation or gel filtration of samples of human or rat plasma incubated with [3H]dolichol suspensions also showed that the labeled material became associated with the same plasma protein fractions as in the in vivo studies. Evidence was obtained to indicate that dolichol is specifically associated with the high density lipoprotein fraction of plasma. The possible role of high density lipoproteins as a vehicle for dolichol transport and the problems involved in the binding of this long moleculare are discussed."}
{"id": "PMID:188483", "title": "Neuraminic acid-specific modification and tritium labelling of gangliosides.", "content": "1. A crude ganglioside mixture and pure GM1 and GD1a from bovine brain grey matter were prepared on a large scale. 2. The C7- and G8-analogues of NeuNAc were prepared from Collocalia mucoid and their structures established by gas-liquid chromatography and mass spectrometry. 3. Using model compounds in addition to various gangliosides, the conditions for the periodate oxidation and subsequent borohydride reduction of gangliosides were investigated with regard to the yield of C7- and C8-analogues of NeuNAc and the integrity of other monosaccharides in the oligosaccharide chain. These conditions were optimised to yield maximum C8-NeuNAc production and low C7-NeuNAc formation. Thus products were obtained which closely resemble the native gangliosides. 4. Using boro [3H] hydride, ganglioside derivatives with high specific radioactivity were prepared for the first time, containing either NeuNAc and labelled C8-NeuNAc or mainly labelled C7-NeuNAc depending on the prevailing conditions.", "contents": "Neuraminic acid-specific modification and tritium labelling of gangliosides. 1. A crude ganglioside mixture and pure GM1 and GD1a from bovine brain grey matter were prepared on a large scale. 2. The C7- and G8-analogues of NeuNAc were prepared from Collocalia mucoid and their structures established by gas-liquid chromatography and mass spectrometry. 3. Using model compounds in addition to various gangliosides, the conditions for the periodate oxidation and subsequent borohydride reduction of gangliosides were investigated with regard to the yield of C7- and C8-analogues of NeuNAc and the integrity of other monosaccharides in the oligosaccharide chain. These conditions were optimised to yield maximum C8-NeuNAc production and low C7-NeuNAc formation. Thus products were obtained which closely resemble the native gangliosides. 4. Using boro [3H] hydride, ganglioside derivatives with high specific radioactivity were prepared for the first time, containing either NeuNAc and labelled C8-NeuNAc or mainly labelled C7-NeuNAc depending on the prevailing conditions."}
{"id": "PMID:188484", "title": "Study of the long chain bases of sphingomyelin of Entomophthora coronata.", "content": "Sphingomyelin was isolated from a strain of Entomophthora coronata, a fungus pathogenic for humans. After hydrolysis, the long chain bases were converted to their dinitrophenyl (N2pH) derivatives and the aldehydes prepared by oxidizing these compounds with periodic acid. The aldehydes were studied by gas chromatography. Twelve different aldehydes were identified, the chain distributiion ranging from C14 to C17. The prominent chains were unsaturated. Straight and branched chains were found. The most abundant parent base which formed 52% of the total aldehyde was a 1,3-dihydroxy-2-aminohexadecene.", "contents": "Study of the long chain bases of sphingomyelin of Entomophthora coronata. Sphingomyelin was isolated from a strain of Entomophthora coronata, a fungus pathogenic for humans. After hydrolysis, the long chain bases were converted to their dinitrophenyl (N2pH) derivatives and the aldehydes prepared by oxidizing these compounds with periodic acid. The aldehydes were studied by gas chromatography. Twelve different aldehydes were identified, the chain distributiion ranging from C14 to C17. The prominent chains were unsaturated. Straight and branched chains were found. The most abundant parent base which formed 52% of the total aldehyde was a 1,3-dihydroxy-2-aminohexadecene."}
{"id": "PMID:188485", "title": "Interaction of apoliprotein C-III with phosphatidylcholine vesicles. Dependence of aproprotein-phospholipid complex formation on vesicle structure.", "content": "We have studied the interaction of an apolipoprotein from human very low density lipoproteins (apoC-III) with egg yolk phosphatidylcholine in the form of single- and multi-bilayer vesicles. The reactivity of single-bilayer vesicles with apoC-III appears to be greater than that of the multi-bilayer vesicles according to several thermodynamic and spectrosconic criteria. In the complexes formed by the association of apoC-III with single-bilayer vesicles, the alpha-helical content of the peptide backbone and the apolarity of the environment around the tryptophan residues are greater than that observed in the complexes formed with the multibilayer vesicles. A higher yield and more homogeneous density distribution of lipid-apoprotein complexes results from the interaction of apoC-III with the single-bilayer vesicles relative to those obtained with the multi-bilayer vesicles. The enthalpy of association of apoC-III with phospholipid was greater for the single-shelled vesicles (25 kcal/mol apoC-III) than for the multi-shelled ones (18 kcal/mol apoC-III). The difference in reactivity of these two types of liposomes is not due to a difference in their fluidities since their fatty acid compositions are identical, but may be due to a difference in their areas of sterically accessible phospholipid, their permeabilities to the apoprotein, their radii of curvation, or a combination of these factors.", "contents": "Interaction of apoliprotein C-III with phosphatidylcholine vesicles. Dependence of aproprotein-phospholipid complex formation on vesicle structure. We have studied the interaction of an apolipoprotein from human very low density lipoproteins (apoC-III) with egg yolk phosphatidylcholine in the form of single- and multi-bilayer vesicles. The reactivity of single-bilayer vesicles with apoC-III appears to be greater than that of the multi-bilayer vesicles according to several thermodynamic and spectrosconic criteria. In the complexes formed by the association of apoC-III with single-bilayer vesicles, the alpha-helical content of the peptide backbone and the apolarity of the environment around the tryptophan residues are greater than that observed in the complexes formed with the multibilayer vesicles. A higher yield and more homogeneous density distribution of lipid-apoprotein complexes results from the interaction of apoC-III with the single-bilayer vesicles relative to those obtained with the multi-bilayer vesicles. The enthalpy of association of apoC-III with phospholipid was greater for the single-shelled vesicles (25 kcal/mol apoC-III) than for the multi-shelled ones (18 kcal/mol apoC-III). The difference in reactivity of these two types of liposomes is not due to a difference in their fluidities since their fatty acid compositions are identical, but may be due to a difference in their areas of sterically accessible phospholipid, their permeabilities to the apoprotein, their radii of curvation, or a combination of these factors."}
{"id": "PMID:188486", "title": "Control of long chain fatty acid oxidation in heart mitochondria as studied by spin labeling.", "content": "Spin-labeled stearic acid is shown to exhibit the same beta-oxidation kinetics as normal stearic acid. ESR spectra recorded in conditions allowing beta-oxidation indicate that membrane-bound fatty acids can be directly beta-oxidized and that the rate of this reaction depends on the concentration of albumin in the medium. The regulating function of albumin and pool role of the lipidic phase of the mitochondrial membranes are discussed.", "contents": "Control of long chain fatty acid oxidation in heart mitochondria as studied by spin labeling. Spin-labeled stearic acid is shown to exhibit the same beta-oxidation kinetics as normal stearic acid. ESR spectra recorded in conditions allowing beta-oxidation indicate that membrane-bound fatty acids can be directly beta-oxidized and that the rate of this reaction depends on the concentration of albumin in the medium. The regulating function of albumin and pool role of the lipidic phase of the mitochondrial membranes are discussed."}
{"id": "PMID:188487", "title": "[Possible role of free radicals in the transformations and mechanism of physiological action of vitamin D].", "content": "Deficiency of vitamine D is accompanied with a decrease of ESR signal intensity from g = 2.003, as well as of the signals with g = 1.94 and gav. = 2.25 in the liver and kidneys of young rats. Injection of 2.5 g ergocalciferole (vitamine D2) to these animals results in a complete or partial normalization of the intensity of these signals during 6--16 hrs and an increase of the ESR signal intensity from g = 2.003 in small intestine mucosa.", "contents": "[Possible role of free radicals in the transformations and mechanism of physiological action of vitamin D]. Deficiency of vitamine D is accompanied with a decrease of ESR signal intensity from g = 2.003, as well as of the signals with g = 1.94 and gav. = 2.25 in the liver and kidneys of young rats. Injection of 2.5 g ergocalciferole (vitamine D2) to these animals results in a complete or partial normalization of the intensity of these signals during 6--16 hrs and an increase of the ESR signal intensity from g = 2.003 in small intestine mucosa."}
{"id": "PMID:188491", "title": "[EPR and low temperature spectrophotometric study of the phototransformation products of bacteriorhodopsin].", "content": "It is shown that BR and intermediate products of its phototransformation P600, P550 and P415 (the maximum at -196 degrees C at 419 nm) are not paramagnetic. Illumination of samples containing P415 (P419) at -- 196 degrees C with light in the region of 360-480 nm results in the formation of paramagnetic centres with a sunglet spectrum deltaH=18 Oe and g=2.002 (R1). In parallel formation of a new photoproduct P421 in the absorption spectrum is observed. During subsequent heating at -140 degrees C formation of an asymmetric signal with deltaH=45 Oe and g=2.006 and g=2.03 was observed. In the absorption spectra a dark transition. P421-P565 was observed under the same conditions. P565 differs from initial BR P570 as to its photochemical properties. R1 is identified as retinal radical, R2 as a peroxide radical of the BR-complex lipids. Paramagnetic, spectral, and photochemical properties of some products of BR transformation are compared. A scheme of oxidative-phosphorylation processes with participation of Mn ions in BR phototransformation.", "contents": "[EPR and low temperature spectrophotometric study of the phototransformation products of bacteriorhodopsin]. It is shown that BR and intermediate products of its phototransformation P600, P550 and P415 (the maximum at -196 degrees C at 419 nm) are not paramagnetic. Illumination of samples containing P415 (P419) at -- 196 degrees C with light in the region of 360-480 nm results in the formation of paramagnetic centres with a sunglet spectrum deltaH=18 Oe and g=2.002 (R1). In parallel formation of a new photoproduct P421 in the absorption spectrum is observed. During subsequent heating at -140 degrees C formation of an asymmetric signal with deltaH=45 Oe and g=2.006 and g=2.03 was observed. In the absorption spectra a dark transition. P421-P565 was observed under the same conditions. P565 differs from initial BR P570 as to its photochemical properties. R1 is identified as retinal radical, R2 as a peroxide radical of the BR-complex lipids. Paramagnetic, spectral, and photochemical properties of some products of BR transformation are compared. A scheme of oxidative-phosphorylation processes with participation of Mn ions in BR phototransformation."}
{"id": "PMID:188488", "title": "[Complex formation of spin-labeled trideoxyadenylate with polyribouridylic acid].", "content": "It is shown that the ESR spectra of triple-stranded complex formed by the polyribouridylic acid with the trideoxyadenylate spin-labelled on terminal phosphate is a superposition of the signals with strongly different width of HFS-components. This result is a structural support of the early proposed supposition about the irregular relative orientations of the oligomers in the triple-stranded complexes of oligoadenylates with poly-U.", "contents": "[Complex formation of spin-labeled trideoxyadenylate with polyribouridylic acid]. It is shown that the ESR spectra of triple-stranded complex formed by the polyribouridylic acid with the trideoxyadenylate spin-labelled on terminal phosphate is a superposition of the signals with strongly different width of HFS-components. This result is a structural support of the early proposed supposition about the irregular relative orientations of the oligomers in the triple-stranded complexes of oligoadenylates with poly-U."}
{"id": "PMID:188492", "title": "[Mechanism of oxidative phosphorylation. I. Role of the respiratory chain].", "content": "Mitochondria of white rat brain increased the respiration on succinate in response to ADP addition; in the presence of after NADH the respiration remained unchanged or decreased ofter addition ADP. When organelles were suspended in water distilled in the concentration of 3 mg of protein/ml and kept at melting ice temperature for 24 hours the response of mitochondria to ADP was not changed. Stechiometric relation between the number of electron of the oxidized substrate and absorbed by oxygen depended on ADP during succinate oxidation and did not change on NADH. ADP phosphorylation is suggested to proceed on the stage of the substrate dehydrogenation, rather than on the cytochrome part of the respiratory chain.", "contents": "[Mechanism of oxidative phosphorylation. I. Role of the respiratory chain]. Mitochondria of white rat brain increased the respiration on succinate in response to ADP addition; in the presence of after NADH the respiration remained unchanged or decreased ofter addition ADP. When organelles were suspended in water distilled in the concentration of 3 mg of protein/ml and kept at melting ice temperature for 24 hours the response of mitochondria to ADP was not changed. Stechiometric relation between the number of electron of the oxidized substrate and absorbed by oxygen depended on ADP during succinate oxidation and did not change on NADH. ADP phosphorylation is suggested to proceed on the stage of the substrate dehydrogenation, rather than on the cytochrome part of the respiratory chain."}
{"id": "PMID:188493", "title": "[Spike tranfer in statistical neuron assemblies. II. Neuron--nonlinear spike source].", "content": "The mathematical model of the neuron function is known to rely on space summing of excitement. The spikes contribute to the inner state of the neuron the farther from cell soma the synapses are located. The difference between excitatory and inhibitory effect results in spike firing if only neural firing threshold is achieved. The values of spike flux have been estimated on the basis of the model of CA3 sector of the Hippocampus and were found to be 15 divided by 35 imp/s.", "contents": "[Spike tranfer in statistical neuron assemblies. II. Neuron--nonlinear spike source]. The mathematical model of the neuron function is known to rely on space summing of excitement. The spikes contribute to the inner state of the neuron the farther from cell soma the synapses are located. The difference between excitatory and inhibitory effect results in spike firing if only neural firing threshold is achieved. The values of spike flux have been estimated on the basis of the model of CA3 sector of the Hippocampus and were found to be 15 divided by 35 imp/s."}
{"id": "PMID:188489", "title": "[Left-helical conformation (type poly-L-proline II) of the polypeptide chain of adrenocorticotropic hormone in water].", "content": "By circular dichroism method the nature of the secondary structure of owine and bovine adrenocroticotropic hormone in water has been studied. An analysis of circular dichrosim spectra and their dependence on temperature point to a left-helical conformation (of the poly-L-proline II type) of the polypeptide chain of adrenocorticopic hormone in water.", "contents": "[Left-helical conformation (type poly-L-proline II) of the polypeptide chain of adrenocorticotropic hormone in water]. By circular dichroism method the nature of the secondary structure of owine and bovine adrenocroticotropic hormone in water has been studied. An analysis of circular dichrosim spectra and their dependence on temperature point to a left-helical conformation (of the poly-L-proline II type) of the polypeptide chain of adrenocorticopic hormone in water."}
{"id": "PMID:188490", "title": "[Interaction of spin-labeled saturated and unsaturated fatty acid derivatives with biological membrane lipid and protein components].", "content": "Interaction of saturated and unsaturated derivatives of spin-labelled fatty acids (2,2,6,6-tetramethyl-4-palmitoylpiperidil-l-oxyl (I) and synthetized by us 2,2,6,6-tetramethyl-4-oleoylpiperidil-1-oxyl (II) with sarcoplasmic reticulum membranes, retina rod outer segments and erythorocyte ghosts was studied. ESR spectra of the probe I are practically unresolved singlets, whereas ESR spectra of the probe II appear as more of less resolved triplet signals. The difference in ESR spectra of the probes I and II is the result of distribution of the probe I in pure lipid regions of membranes, the probe II being located both in lipid bilayer and hydrophobic areas of proteins.", "contents": "[Interaction of spin-labeled saturated and unsaturated fatty acid derivatives with biological membrane lipid and protein components]. Interaction of saturated and unsaturated derivatives of spin-labelled fatty acids (2,2,6,6-tetramethyl-4-palmitoylpiperidil-l-oxyl (I) and synthetized by us 2,2,6,6-tetramethyl-4-oleoylpiperidil-1-oxyl (II) with sarcoplasmic reticulum membranes, retina rod outer segments and erythorocyte ghosts was studied. ESR spectra of the probe I are practically unresolved singlets, whereas ESR spectra of the probe II appear as more of less resolved triplet signals. The difference in ESR spectra of the probes I and II is the result of distribution of the probe I in pure lipid regions of membranes, the probe II being located both in lipid bilayer and hydrophobic areas of proteins."}
{"id": "PMID:188494", "title": "[Localization of unpaired electrons in molecules of lysozyme substrate-inhibitors. I. N-acetylglucosamine].", "content": "Electron structure of N-acetylglucoseamine molecule and its ion-radicals has been studied by quantum-chemical methods CNDO2 and JNDO, and by ESR as well. N-acetyl group is shown to be the only electron acceptor group of AGA molecule. Phototransformations of paramagnetic centres are studied at different pH values.", "contents": "[Localization of unpaired electrons in molecules of lysozyme substrate-inhibitors. I. N-acetylglucosamine]. Electron structure of N-acetylglucoseamine molecule and its ion-radicals has been studied by quantum-chemical methods CNDO2 and JNDO, and by ESR as well. N-acetyl group is shown to be the only electron acceptor group of AGA molecule. Phototransformations of paramagnetic centres are studied at different pH values."}
{"id": "PMID:188495", "title": "[IR-spectroscopic study of lecithin and cholesterol layers adsorbed on Aerosil].", "content": "The IR-study of adsorbed layers of lecithin and cholesterol on aerosil was carried out. It was found that lipid molecules interact with adsorbent by means of hydrogen bonds with free surface hydroxyls. The structure of lipid layers on the surface of aerosil is discussed.", "contents": "[IR-spectroscopic study of lecithin and cholesterol layers adsorbed on Aerosil]. The IR-study of adsorbed layers of lecithin and cholesterol on aerosil was carried out. It was found that lipid molecules interact with adsorbent by means of hydrogen bonds with free surface hydroxyls. The structure of lipid layers on the surface of aerosil is discussed."}
{"id": "PMID:188502", "title": "Formation of lipid inclusions in normal human leukocytes.", "content": "Normal peripheral blood leukocytes left standing at room temperature develop large inclusions which increase in number and size with time of incubation. The formation and nature of these inclusions were investigated. At 0 hour the structures were present in only 1% of the cells, whereas at 48 hr, they were in virtually all neutrophils and monocytes. Ultrastructurally, the globules measured 0.5-1.5 mu in diameter and they were usually not membrane bound. Histochemical analysis indicated that they were lipid in nature. The inclusions were separated on a sucrose density gradient and their isolation was confirmed by electron microscopy. Thin-layer chromatography of the isolated globules suggested that they consisted predominantly of triglycerides. Since it is known that the cells synthesize triglycerides at rest, it was postulated that the structures may represent the storage form for free fatty acids which may be utilized for membrane synthesis during phagocytosis.", "contents": "Formation of lipid inclusions in normal human leukocytes. Normal peripheral blood leukocytes left standing at room temperature develop large inclusions which increase in number and size with time of incubation. The formation and nature of these inclusions were investigated. At 0 hour the structures were present in only 1% of the cells, whereas at 48 hr, they were in virtually all neutrophils and monocytes. Ultrastructurally, the globules measured 0.5-1.5 mu in diameter and they were usually not membrane bound. Histochemical analysis indicated that they were lipid in nature. The inclusions were separated on a sucrose density gradient and their isolation was confirmed by electron microscopy. Thin-layer chromatography of the isolated globules suggested that they consisted predominantly of triglycerides. Since it is known that the cells synthesize triglycerides at rest, it was postulated that the structures may represent the storage form for free fatty acids which may be utilized for membrane synthesis during phagocytosis."}
{"id": "PMID:188504", "title": "Transport of monoamines in membranes of adrenal chromaffin granules: physiological and pharmacological aspects.", "content": "The membranes of isolated bovine adrenal chromaffin granules take up catecholamines by an ATP-dependent process which fulfills many criteria of a carriermediated energy-requiring transport. This transport together with an intragranular mechanism probably explains the high storage capacity of the chromaffin granules for catecholamines. 5.2 Other amines (e.g. 5-hydroxytryptamine (5HT), octopamine) are also taken up by the membranes, but to a different degree. This probably explains why amines normally not present in storage organelles, if available in increased amounts, may accumulate within these organelles and function as false neurohumoral transmitters. 5.3. Two mechanisms of amine uptake seem to exist at the level of the granule membranes, one reserpine-sensitive (transporting, for instance, catecholamines and 5HT), and one reserpine-resistant (transporting tryptamine and partly metaraminol). Both mechanisms depend on ATP. 5.4. Chlorpromazine interferes with the reserpine-sensitive as well as the reserpine-resistant uptake of noradrenaline (NA) by granule membranes to a similar degree. Consequently the mechanism of action of neuroleptics and reserpine at the granule membrane level are probably different. 5.5. There is only an incomplete parallelism between the inhibition of NA-uptake by granule membranes in vitro and the degree of enhancement of neuronal DA turnover in vivo caused by various neuroleptics. Therefore, factors other than interference with the amine transport through the granule membranes must be co-determinant in the neuroleptic induced enhancement of DA turnover in vivo.", "contents": "Transport of monoamines in membranes of adrenal chromaffin granules: physiological and pharmacological aspects. The membranes of isolated bovine adrenal chromaffin granules take up catecholamines by an ATP-dependent process which fulfills many criteria of a carriermediated energy-requiring transport. This transport together with an intragranular mechanism probably explains the high storage capacity of the chromaffin granules for catecholamines. 5.2 Other amines (e.g. 5-hydroxytryptamine (5HT), octopamine) are also taken up by the membranes, but to a different degree. This probably explains why amines normally not present in storage organelles, if available in increased amounts, may accumulate within these organelles and function as false neurohumoral transmitters. 5.3. Two mechanisms of amine uptake seem to exist at the level of the granule membranes, one reserpine-sensitive (transporting, for instance, catecholamines and 5HT), and one reserpine-resistant (transporting tryptamine and partly metaraminol). Both mechanisms depend on ATP. 5.4. Chlorpromazine interferes with the reserpine-sensitive as well as the reserpine-resistant uptake of noradrenaline (NA) by granule membranes to a similar degree. Consequently the mechanism of action of neuroleptics and reserpine at the granule membrane level are probably different. 5.5. There is only an incomplete parallelism between the inhibition of NA-uptake by granule membranes in vitro and the degree of enhancement of neuronal DA turnover in vivo caused by various neuroleptics. Therefore, factors other than interference with the amine transport through the granule membranes must be co-determinant in the neuroleptic induced enhancement of DA turnover in vivo."}
{"id": "PMID:188505", "title": "[Pathophysiology of the membrane function in the kidney].", "content": "The examples of tubular proteinuria, postobstructive diuresis, tubular function in terminal renal failure and the hereditary defects of tubular transport mechanisms are used to demonstrate the difficulty in elucidating defects of renal membrane transports in man. She is caused by the impossibility of applying the appropriate techniques to evaluate membrane functions in man and by the complexity of human disease. The rapidly growing knowledge of physiologic membrane functions in the kidney should however enable some progress in the field of human pathophysiology in a not too remote future.", "contents": "[Pathophysiology of the membrane function in the kidney]. The examples of tubular proteinuria, postobstructive diuresis, tubular function in terminal renal failure and the hereditary defects of tubular transport mechanisms are used to demonstrate the difficulty in elucidating defects of renal membrane transports in man. She is caused by the impossibility of applying the appropriate techniques to evaluate membrane functions in man and by the complexity of human disease. The rapidly growing knowledge of physiologic membrane functions in the kidney should however enable some progress in the field of human pathophysiology in a not too remote future."}
{"id": "PMID:188506", "title": "Cyclic AMP in the CSF of patients with schizophrenia.", "content": "The dopamine hypothesis of schizophrenia proposes that schizophrenia is associated with increased brain dopaminergic function. Because dopamine is thought to stimulate the production of cyclic AMP in the brain, we hypothesized that CSF cyclic AMP would be increased in schizophrenia. Cyclic AMP in the CSF was determined in 19 schizophrenic patients who had not received neuroleptic treatment in the preceding two weeks. No significant difference could be shown between CSF cyclic AMP in these patients and CSF cyclic AMP in 10 psychiatrically normal controls.", "contents": "Cyclic AMP in the CSF of patients with schizophrenia. The dopamine hypothesis of schizophrenia proposes that schizophrenia is associated with increased brain dopaminergic function. Because dopamine is thought to stimulate the production of cyclic AMP in the brain, we hypothesized that CSF cyclic AMP would be increased in schizophrenia. Cyclic AMP in the CSF was determined in 19 schizophrenic patients who had not received neuroleptic treatment in the preceding two weeks. No significant difference could be shown between CSF cyclic AMP in these patients and CSF cyclic AMP in 10 psychiatrically normal controls."}
{"id": "PMID:188507", "title": "The radiology of sclerosteosis.", "content": "Sclerosteosis is an unusual disorder in which increased skeletal density is associated with abnormalities of bony modelling. The condition is progressive and complications arise due to cranial nerve involvement. Death from raised intracranial pressure occurs in early adulthood. In order to define the range and extent of the bony abnormalities, the radiographic features of 18 affected individuals have been analysed. The recognition of characteristic changes permits diagnostic precision.", "contents": "The radiology of sclerosteosis. Sclerosteosis is an unusual disorder in which increased skeletal density is associated with abnormalities of bony modelling. The condition is progressive and complications arise due to cranial nerve involvement. Death from raised intracranial pressure occurs in early adulthood. In order to define the range and extent of the bony abnormalities, the radiographic features of 18 affected individuals have been analysed. The recognition of characteristic changes permits diagnostic precision."}
{"id": "PMID:188509", "title": "Mixed vascular deformities of the lower limbs, with particular reference to lymphography and surgical treatment.", "content": "A series of patients with congenital blood and lymph anomalies of the lower limb investigated and treated at St Thomas's Hospital, London, are reviewed. They fell into three classes: (1) those in which the venous element predominated (Klippel and other syndromes), (2) those with arteriovenous shunts and (3) those with angiomas of blood or lymph vessels scattered through the limb (diffuse mixed angiomas). Most of the patients were investigated by angiography (of blood or lymph systems) as well as by plethysmography, dermal temperature measurements and other techniques in the thermal laboratory. Phlebography showed most abnormalities in the Klippel group and was useful in delineating them before operation. The importance of confirming the existence of an adequate deep venous circulation prior to ablation of abnormal superficial vessels is emphasized. Arteriography showed most abnormalities in the group with suspected arteriovenous shunts. The most commonly performed operations in this group were for control of overgrowth of the limb or for ulceration. Lymphography showed many of the Klippel group to suffer from insufficiency of the main pathways, either aplasia or hypoplasia. In addition many had vesicles, fistulas and lymph cysts. Patients in the arteriovenous shunt group had large hyperplastic lymph pathways, which were possibly either congenital or a hypertrophic response. One hundred and thirty-eight operations were performed in 46 patients for a variety of lesions and disabilities. These are reviewed. The scope and benefit of surgery in these children are greater than has been accepted in the past. Three patients required amputation of a limb. There were 5 deaths in the series, 4 of these being in the scattered angioma group and in patients in whom the deformities extended beyond the limb into the trunk.", "contents": "Mixed vascular deformities of the lower limbs, with particular reference to lymphography and surgical treatment. A series of patients with congenital blood and lymph anomalies of the lower limb investigated and treated at St Thomas's Hospital, London, are reviewed. They fell into three classes: (1) those in which the venous element predominated (Klippel and other syndromes), (2) those with arteriovenous shunts and (3) those with angiomas of blood or lymph vessels scattered through the limb (diffuse mixed angiomas). Most of the patients were investigated by angiography (of blood or lymph systems) as well as by plethysmography, dermal temperature measurements and other techniques in the thermal laboratory. Phlebography showed most abnormalities in the Klippel group and was useful in delineating them before operation. The importance of confirming the existence of an adequate deep venous circulation prior to ablation of abnormal superficial vessels is emphasized. Arteriography showed most abnormalities in the group with suspected arteriovenous shunts. The most commonly performed operations in this group were for control of overgrowth of the limb or for ulceration. Lymphography showed many of the Klippel group to suffer from insufficiency of the main pathways, either aplasia or hypoplasia. In addition many had vesicles, fistulas and lymph cysts. Patients in the arteriovenous shunt group had large hyperplastic lymph pathways, which were possibly either congenital or a hypertrophic response. One hundred and thirty-eight operations were performed in 46 patients for a variety of lesions and disabilities. These are reviewed. The scope and benefit of surgery in these children are greater than has been accepted in the past. Three patients required amputation of a limb. There were 5 deaths in the series, 4 of these being in the scattered angioma group and in patients in whom the deformities extended beyond the limb into the trunk."}
{"id": "PMID:188510", "title": "Cancer of the large bowel in the African: a 15-year survey at Kinshasa University Hospital, Za\u00efre.", "content": "In a 15-year survey at Kinshasa University Hospital, 954 solid cancers were recorded. Among these, 46 malignant tumours arose in the colon, rectum and anal canal, a proportion of 4-8 per cent. A review of the patients' age and clinical presentation, and pathology and aetiology of the tumours revealed that: 1. The incidence of this cancer in young Africans is higher than in Western countries. 2. The clinical presentation of this illness in young people is frequently unusual, but older African patients commonly present with classic symptoms. 3. The incidence of mucous carcinoma tends to be higher, but could be explained by the larger number of young people suffering from the condition. 4. Intestinal amoebiasis was associated with cancer in 3 cases. Its significance remains uncertain.", "contents": "Cancer of the large bowel in the African: a 15-year survey at Kinshasa University Hospital, Za\u00efre. In a 15-year survey at Kinshasa University Hospital, 954 solid cancers were recorded. Among these, 46 malignant tumours arose in the colon, rectum and anal canal, a proportion of 4-8 per cent. A review of the patients' age and clinical presentation, and pathology and aetiology of the tumours revealed that: 1. The incidence of this cancer in young Africans is higher than in Western countries. 2. The clinical presentation of this illness in young people is frequently unusual, but older African patients commonly present with classic symptoms. 3. The incidence of mucous carcinoma tends to be higher, but could be explained by the larger number of young people suffering from the condition. 4. Intestinal amoebiasis was associated with cancer in 3 cases. Its significance remains uncertain."}
{"id": "PMID:188513", "title": "Warts and wart virus antibodies in patients with systemic lupus erythematosus.", "content": "Warts were found in 25 out of 56 patients with definite or probable systemic lupus erythematosus (SLE) but in only 19 out of 160 control patients. Warts were particularly prevalent in elderly patients with SLE. The corticosteroid and antimalarial drugs used to treat SLE did not influence the frequency of warts. Wart-virus antibodies were found significantly less often in patients with SLE than in controls: antibodies were detected in 23 out of 51 patients and in 40 out of 54 controls. Ihe findings suggest that some deficiency in the immune mechanisms of patients with SLE predisposes them to develop warts. There was an inverse correlation among the patients with SLE between the occurrence of warts and rheumatoid factor activity. This suggests that rheumatoid factor may interfere with resistance to warts.", "contents": "Warts and wart virus antibodies in patients with systemic lupus erythematosus. Warts were found in 25 out of 56 patients with definite or probable systemic lupus erythematosus (SLE) but in only 19 out of 160 control patients. Warts were particularly prevalent in elderly patients with SLE. The corticosteroid and antimalarial drugs used to treat SLE did not influence the frequency of warts. Wart-virus antibodies were found significantly less often in patients with SLE than in controls: antibodies were detected in 23 out of 51 patients and in 40 out of 54 controls. Ihe findings suggest that some deficiency in the immune mechanisms of patients with SLE predisposes them to develop warts. There was an inverse correlation among the patients with SLE between the occurrence of warts and rheumatoid factor activity. This suggests that rheumatoid factor may interfere with resistance to warts."}
{"id": "PMID:188515", "title": "Non-B hepatitis in Melbourne: a serological study of hepatitis A virus infection.", "content": "A study was performed to establish the value of immune adherence haemagglutination tests for antibody to hepatitis A virus in the diagnosis of non-B hepatitis. Infection with hepatitis A virus was confirmed in 14 out of 16 patients from six families and seven out of nine patients in whom the source of infection was unknown. One additional patient, who had had two episodes of jaundice, was shown to have had an attack of hepatitis A followed by an attack of hepatitis B. In patients with acute hepatitis A antibody detectable by immune adherence haemagglutination becomes detectable three or four weeks after the onset of symptoms and reaches peak levels about five weeks later.", "contents": "Non-B hepatitis in Melbourne: a serological study of hepatitis A virus infection. A study was performed to establish the value of immune adherence haemagglutination tests for antibody to hepatitis A virus in the diagnosis of non-B hepatitis. Infection with hepatitis A virus was confirmed in 14 out of 16 patients from six families and seven out of nine patients in whom the source of infection was unknown. One additional patient, who had had two episodes of jaundice, was shown to have had an attack of hepatitis A followed by an attack of hepatitis B. In patients with acute hepatitis A antibody detectable by immune adherence haemagglutination becomes detectable three or four weeks after the onset of symptoms and reaches peak levels about five weeks later."}
{"id": "PMID:188519", "title": "Differences between murine C1300 neuroblastoma clones detected by rosette formation with nerve growth factor-coated sheep red blood cells.", "content": "The expression of receptors for nerve growth factor (NGF) on the cell surface was assayed by rosette formation with ligand-coated sheep red blood cells (SRBC). Cell clones derived from the murine C1300 neuroblastoma and from hybrids between a neuroblastoma clone and L cell clones showed a wide variation in the capacity to form rosettes with NGF-coated SRBC. All the neuroblastoma, L cell and hybrid clones formed rosettes with phytohemagglutinin-coated SRBC and none formed rosettes with cytochrome c- or ferritin-coated SRBC or with SRBC not coated with ligand.", "contents": "Differences between murine C1300 neuroblastoma clones detected by rosette formation with nerve growth factor-coated sheep red blood cells. The expression of receptors for nerve growth factor (NGF) on the cell surface was assayed by rosette formation with ligand-coated sheep red blood cells (SRBC). Cell clones derived from the murine C1300 neuroblastoma and from hybrids between a neuroblastoma clone and L cell clones showed a wide variation in the capacity to form rosettes with NGF-coated SRBC. All the neuroblastoma, L cell and hybrid clones formed rosettes with phytohemagglutinin-coated SRBC and none formed rosettes with cytochrome c- or ferritin-coated SRBC or with SRBC not coated with ligand."}
{"id": "PMID:188520", "title": "Neuronal activity specific to REM sleep and its relationship to breathing.", "content": "The search for the neural substrate of a state of consciousness has led to the expectation that there may be neurons which discharge tonically and rhythmically during that state alone. We have now recorded in the cat the first evidence of neurons whose rhythmic discharge is consistent with the hypothesis of a tonically active neural substrate for rapid eye movement (REM) sleep. These neurons, located in the area of gigantocellular and lateral medullary tegmental fields, begin rhythmically discharging simultaneously with the cortical desynchronization at REM sleep onset and cease firing at arousal from REM; they are essentially silent at all other times. Modulations of the discharge rate correlate with the phasic events of REM sleep, such as ataxic breathing and eye movement bursts. In addition, there is a high correlation between their discharge rate and respiratory frequency analyzed on a breath-by-breath basis. The significant rhythmicity of their discharge coupled with high REM selectivity contrasts them with putative REM generators reported by others in the pons and suggests their crucial role in REM generation.", "contents": "Neuronal activity specific to REM sleep and its relationship to breathing. The search for the neural substrate of a state of consciousness has led to the expectation that there may be neurons which discharge tonically and rhythmically during that state alone. We have now recorded in the cat the first evidence of neurons whose rhythmic discharge is consistent with the hypothesis of a tonically active neural substrate for rapid eye movement (REM) sleep. These neurons, located in the area of gigantocellular and lateral medullary tegmental fields, begin rhythmically discharging simultaneously with the cortical desynchronization at REM sleep onset and cease firing at arousal from REM; they are essentially silent at all other times. Modulations of the discharge rate correlate with the phasic events of REM sleep, such as ataxic breathing and eye movement bursts. In addition, there is a high correlation between their discharge rate and respiratory frequency analyzed on a breath-by-breath basis. The significant rhythmicity of their discharge coupled with high REM selectivity contrasts them with putative REM generators reported by others in the pons and suggests their crucial role in REM generation."}
{"id": "PMID:188521", "title": "Absence of morphine antagonism of prostaglandin E1-stimulated [3H]3',5'-cyclic adenosine monophosphate accumulation in a rat brain mince system.", "content": "Prostaglandin E1 (PGE1)-stimulated [3H]3',5'-cyclic adenosine monophosphate ([3H]cAMP) accumulation was studied in a rat brain mince system to determine if stimulation of net [3H]cAMP accumulation could be prevented or reversed by morphine. Incubated minces of whole brain minus cerebellum were prepared from naive, acutely morphine-treated, and morphine-tolerant and withdrawing rats. Basal levels of [3H]cAMP accumulation in the three groups were equal within experimental limits. Morphine addition to the PGE1-stimulated minces did not prevent or reverse stimulation of [3H]cAMP accumulation in any of the three experimental groups. The data do not support the thesis that PGE1-stimulated cAMP accumulation in brain is a locus of opiate action in the phenomena of opiate analgesia, tolerance, and dependence.", "contents": "Absence of morphine antagonism of prostaglandin E1-stimulated [3H]3',5'-cyclic adenosine monophosphate accumulation in a rat brain mince system. Prostaglandin E1 (PGE1)-stimulated [3H]3',5'-cyclic adenosine monophosphate ([3H]cAMP) accumulation was studied in a rat brain mince system to determine if stimulation of net [3H]cAMP accumulation could be prevented or reversed by morphine. Incubated minces of whole brain minus cerebellum were prepared from naive, acutely morphine-treated, and morphine-tolerant and withdrawing rats. Basal levels of [3H]cAMP accumulation in the three groups were equal within experimental limits. Morphine addition to the PGE1-stimulated minces did not prevent or reverse stimulation of [3H]cAMP accumulation in any of the three experimental groups. The data do not support the thesis that PGE1-stimulated cAMP accumulation in brain is a locus of opiate action in the phenomena of opiate analgesia, tolerance, and dependence."}
{"id": "PMID:188523", "title": "Brain cyclic adenosine 3',5'-monophosphate during depolarization of the cerebral cortical cells in vivo.", "content": "Cyclic AMP (cAMP) was determined in that part of the rat cerebral cortex which was invaded by slow potential change (SPC) accompanying cortical spreading depression (CSD). cAMP was determined at various phases of SPC development and at several time intervals after SPC recovery. At maximum SPC, cAMP was increased by 100% above control and by 116% at the time of SPC recovery. Five, 10 and 15 min after SPC recovery, +54%, +34% and 0% increase in cAMP was found, respectively. The activity of phosphorylase a increased by 112% at SPC recovery (maximal cAMP increase), and by 13% 15 min later (complete cAMP recovery). Some depolarizing agents which differ in their ability to stimulate cAMP formation in vitro (veratridine, cyanide and glutamate) when applied topically onto the cerebral cortex in concentrations evoking CSD (2 mM veratridine, 10 mM cyanide and 100 mM glutamate), induced uniform increase of cAMP by about 100%. The same cAMP augmentation was found in the cortical region under maximum SPC induced by these agents.", "contents": "Brain cyclic adenosine 3',5'-monophosphate during depolarization of the cerebral cortical cells in vivo. Cyclic AMP (cAMP) was determined in that part of the rat cerebral cortex which was invaded by slow potential change (SPC) accompanying cortical spreading depression (CSD). cAMP was determined at various phases of SPC development and at several time intervals after SPC recovery. At maximum SPC, cAMP was increased by 100% above control and by 116% at the time of SPC recovery. Five, 10 and 15 min after SPC recovery, +54%, +34% and 0% increase in cAMP was found, respectively. The activity of phosphorylase a increased by 112% at SPC recovery (maximal cAMP increase), and by 13% 15 min later (complete cAMP recovery). Some depolarizing agents which differ in their ability to stimulate cAMP formation in vitro (veratridine, cyanide and glutamate) when applied topically onto the cerebral cortex in concentrations evoking CSD (2 mM veratridine, 10 mM cyanide and 100 mM glutamate), induced uniform increase of cAMP by about 100%. The same cAMP augmentation was found in the cortical region under maximum SPC induced by these agents."}
{"id": "PMID:188525", "title": "Eye movement-associated discharge in brain stem neurons during desynchronized sleep.", "content": "The relationship between isolated eye movement during desynchronized sleep and unit discharge in the pontine brain stem was investigated during spontaneously occurring desynchronized sleep episodes in cats. Units histologically localized to the gigantocellular tegmental field (FTG) showed the earliest and most prominent discharge rate increases relative to eye movement onset. Inflection points for discharge rate increases of these reticular elements peaked 150-100 msec before eye movement onset and discharge maxima occurred in the time period 50 msec before and 50 msec after eye movement onset. Within the FTG there was a correlation between giant cell density and intensity of discharge rate increases relative to eye movement onset, indicating that the giant cells are the neurons that show this pattern most strongly. The exponential form of the curves of FTG inflection points and discharge maxima is compatible with self-excitation as a mechanism for recruitment in the FTG pool. Units in the central, lateral, and paralemniscal tegmental reticular fields had activity curves qualitatively similar to those of the FTG, but with less intensity of discharge rate change and shorter lead-times. The discharge pattern was quite different in the two other cell groups studied. Many units in the tegmental reticular nucleus had bursts of discharges tightly locked to eye movement onset, while pontine grey units had an irregular pattern and a low degree of phase-locking to eye movement onset. Of the neurons studied, the giant cells of the FTG best satisfy correlational criteria for eye movement generation during desynchronized sleep. These findings support the hypothesis that the FTG is part of a generator system for desynchronized sleep and may contribute directly to the elaboration of the phasic events characterizing that state.", "contents": "Eye movement-associated discharge in brain stem neurons during desynchronized sleep. The relationship between isolated eye movement during desynchronized sleep and unit discharge in the pontine brain stem was investigated during spontaneously occurring desynchronized sleep episodes in cats. Units histologically localized to the gigantocellular tegmental field (FTG) showed the earliest and most prominent discharge rate increases relative to eye movement onset. Inflection points for discharge rate increases of these reticular elements peaked 150-100 msec before eye movement onset and discharge maxima occurred in the time period 50 msec before and 50 msec after eye movement onset. Within the FTG there was a correlation between giant cell density and intensity of discharge rate increases relative to eye movement onset, indicating that the giant cells are the neurons that show this pattern most strongly. The exponential form of the curves of FTG inflection points and discharge maxima is compatible with self-excitation as a mechanism for recruitment in the FTG pool. Units in the central, lateral, and paralemniscal tegmental reticular fields had activity curves qualitatively similar to those of the FTG, but with less intensity of discharge rate change and shorter lead-times. The discharge pattern was quite different in the two other cell groups studied. Many units in the tegmental reticular nucleus had bursts of discharges tightly locked to eye movement onset, while pontine grey units had an irregular pattern and a low degree of phase-locking to eye movement onset. Of the neurons studied, the giant cells of the FTG best satisfy correlational criteria for eye movement generation during desynchronized sleep. These findings support the hypothesis that the FTG is part of a generator system for desynchronized sleep and may contribute directly to the elaboration of the phasic events characterizing that state."}
{"id": "PMID:188529", "title": "[Necrotic enteritis in broiler chickens. III. Study of the factors favoring the multiplication of Clostridium perfringens and the experimental transmission of the disease].", "content": "Necrotic enteritis was reproduced experimentally in two week old broiler chickens by intravenous injection and also by oral administration of a pure culture of Clostridium perfringens. In the first experiment, gross and microscopic intestinal lesions, typical of necrotic enteritis, were observed in all diseased birds and mortality was obtained only in the group of birds that were injected with 0.4 ml or more of the pure culture of the microorganism. In the second experiment, the highest mortality was noted in the group of birds that received orally, in addition to the Clostridium culture, a solution of sodium bicarbonate, to obtain an alkaline intestinal content and opium to decrease the intestinal peristaltism. The gross and microscopie intestinal lesions of the diseased and killed birds were more severe than those observed in the other groups and were similar to those encountered in field outbreaks of necrotic enteritis.", "contents": "[Necrotic enteritis in broiler chickens. III. Study of the factors favoring the multiplication of Clostridium perfringens and the experimental transmission of the disease]. Necrotic enteritis was reproduced experimentally in two week old broiler chickens by intravenous injection and also by oral administration of a pure culture of Clostridium perfringens. In the first experiment, gross and microscopic intestinal lesions, typical of necrotic enteritis, were observed in all diseased birds and mortality was obtained only in the group of birds that were injected with 0.4 ml or more of the pure culture of the microorganism. In the second experiment, the highest mortality was noted in the group of birds that received orally, in addition to the Clostridium culture, a solution of sodium bicarbonate, to obtain an alkaline intestinal content and opium to decrease the intestinal peristaltism. The gross and microscopie intestinal lesions of the diseased and killed birds were more severe than those observed in the other groups and were similar to those encountered in field outbreaks of necrotic enteritis."}
{"id": "PMID:188526", "title": "Cat sleep: a unique first night effect.", "content": "Longitudinal sleep studies in chronically implanted cats revealed a unique first night effect. Unlike other species, during the first 24 hr of sleep recording, the electroencephalogram and reticular formation multiple unit activity revealed more rapid eye movement sleep occurred than during subsequent 24 hr recording sessions. In addition, higher rapid eye movement to slow wave sleep ratios were observed for the first 24 hr as compared to the following days. An increase in wakefulness and decrease in slow wave sleep occurred on the third recording day as compared to the initial 24 hr period. These data have important implications for studies of variables on the sleep pattern of animals.", "contents": "Cat sleep: a unique first night effect. Longitudinal sleep studies in chronically implanted cats revealed a unique first night effect. Unlike other species, during the first 24 hr of sleep recording, the electroencephalogram and reticular formation multiple unit activity revealed more rapid eye movement sleep occurred than during subsequent 24 hr recording sessions. In addition, higher rapid eye movement to slow wave sleep ratios were observed for the first 24 hr as compared to the following days. An increase in wakefulness and decrease in slow wave sleep occurred on the third recording day as compared to the initial 24 hr period. These data have important implications for studies of variables on the sleep pattern of animals."}
{"id": "PMID:188530", "title": "Interferon inducers and foot-and-mouth disease vaccines: influence of two synthetic polynucleotides on antibody response and immunity in guinea pigs and swine.", "content": "Polyriboadenylic-polybouridylic acid enhanced the immunological response of guinea pigs to aqueous foot-and-mouth disease virus vaccine. Polyriboninosinic-polyribocytidylic acid enhanced the early antibody production of swine to oil emulsified foot-and-mouth disease virus vaccine. Polyriboninosinic-polyribocytidylic acid alone did not stimulate resistance to foot-and-mouth disease in swine.", "contents": "Interferon inducers and foot-and-mouth disease vaccines: influence of two synthetic polynucleotides on antibody response and immunity in guinea pigs and swine. Polyriboadenylic-polybouridylic acid enhanced the immunological response of guinea pigs to aqueous foot-and-mouth disease virus vaccine. Polyriboninosinic-polyribocytidylic acid enhanced the early antibody production of swine to oil emulsified foot-and-mouth disease virus vaccine. Polyriboninosinic-polyribocytidylic acid alone did not stimulate resistance to foot-and-mouth disease in swine."}
{"id": "PMID:188527", "title": "Analysis of circulation of neuronal activity in the waking cortex.", "content": "It is well known that the rhythmic activity of the cerebral cortex is closely associated with a highly organized circulation of neuronal impulses through the networks in which the activity develops. The present study has attempted to determine by quantitative methods, the consistency of this circulation and of its association with the cortical waves, over relatively long periods. Cortical gross waves and neuronal activity have been recorded by means of arrays of extracellular microelectrodes, in freely moving cats as well as in cats immobilized with flaxedil. Autocorrelations have been performed on trains of rhythmic waves and on associated clusters of action potentials; cross-correlations and multiple correlations have been performed between waves and action potentials and between action potentials generated by different groups of neurons. It has been found that the rhythmicity of the waves, the rhythmicity of the associated clusters of action potentials,  the time and phase relations between them, and the circulation of neuronal activity through the networks, remain highly consistent over periods as long as two hours.", "contents": "Analysis of circulation of neuronal activity in the waking cortex. It is well known that the rhythmic activity of the cerebral cortex is closely associated with a highly organized circulation of neuronal impulses through the networks in which the activity develops. The present study has attempted to determine by quantitative methods, the consistency of this circulation and of its association with the cortical waves, over relatively long periods. Cortical gross waves and neuronal activity have been recorded by means of arrays of extracellular microelectrodes, in freely moving cats as well as in cats immobilized with flaxedil. Autocorrelations have been performed on trains of rhythmic waves and on associated clusters of action potentials; cross-correlations and multiple correlations have been performed between waves and action potentials and between action potentials generated by different groups of neurons. It has been found that the rhythmicity of the waves, the rhythmicity of the associated clusters of action potentials,  the time and phase relations between them, and the circulation of neuronal activity through the networks, remain highly consistent over periods as long as two hours."}
{"id": "PMID:188531", "title": "Tween 80: a marker for differentiation of hog cholera and bovine viral diarrhea viruses.", "content": "Markers for differentiating hog cholera and bovine viral diarrhea viruses were studied using Tween 80, chloroform, trichlorotrifluoroethane and tri (n-butyl) phosphate. Attenuated A and virulent Ames strains of hog cholera virus were employed. Moreover, the NADL PK-15 cell culture adopted strain and low cell culture passaged Purdue strain of bovine viral diarrhea virus were used. These viruses were reacted with 2,500 micrograms/ml of Tween 80 for one hour at 37 degrees C. When attenuated A and virulent Ames strains of hog cholera virus with titers greater than 10(6) and 10(5) plaque forming units respectively, were reacted with Tween 80 the titer of each strains was reduced by approximately 10(4) plaque forming units of virus. When either strain of bovine viral diarrhea virus was reacted with Tween 80, virus was not detected.", "contents": "Tween 80: a marker for differentiation of hog cholera and bovine viral diarrhea viruses. Markers for differentiating hog cholera and bovine viral diarrhea viruses were studied using Tween 80, chloroform, trichlorotrifluoroethane and tri (n-butyl) phosphate. Attenuated A and virulent Ames strains of hog cholera virus were employed. Moreover, the NADL PK-15 cell culture adopted strain and low cell culture passaged Purdue strain of bovine viral diarrhea virus were used. These viruses were reacted with 2,500 micrograms/ml of Tween 80 for one hour at 37 degrees C. When attenuated A and virulent Ames strains of hog cholera virus with titers greater than 10(6) and 10(5) plaque forming units respectively, were reacted with Tween 80 the titer of each strains was reduced by approximately 10(4) plaque forming units of virus. When either strain of bovine viral diarrhea virus was reacted with Tween 80, virus was not detected."}
{"id": "PMID:188532", "title": "Sulfur amino acid auxotrophy in Micrococcus species isolated from human skin.", "content": "Since methionine and (or) cysteine are required by a large percentage of natural auxotrophic Micrococcus strains isolated from human skin, investigations were directed to determine the specific enzymes affected in sulfur amino acid biosynthesis. Known intermediates in the interrelated cysteine and methionine biosynthetic pathways were tested as growth stimulants. Based on these growth studies, sulfur amino acid auxotrophs were grouped into three cysteine classes and five methionine classes. Selected auxotrophs of M. luteus had deficiencies in ATP sulfurylase (EC 2.7.7.4) and adenosine-5-sulfatophosphate (APS) kinase (EC 2.7.1.25), sulfite reductase (EC 1.8.1.2), serine transacetylase (EC 2.3.1.30), or beta-cystathionase (EC 4.4.1.8) activity; auxotrophs of M. lylae had deficiencies in sulfite reductase and serine transacetylase, beta-cystathionase, or N5, N10-methyltetrahydrofolate reductase (EC 1.1.1.68) activity; all auxotrophs of M. sedentarius tested had deficiencies in N5,N10-methyltetrahydrofolate reductase activity; auxotrophs of M. nishinomiyaensis had deficiencies in adenosine-3-phosphate-5-sulfatophosphate (PAPS) reductase, sulfite reductase, serine transacetylase, or N5,N10-methyltetrahydrofolate reductase activity; auxotrophs of M. varians had deficiencies in APS kinase, PAPS reductase, sulfite reductase, homoserine omicron-transsuccinylase, beta-cystathionase, or N5,N10-methyltetrahydrofolate reductase activity; auxotrophs of M. kristinae had deficiencies in serine transacetylase or cystathionine-gamma-synthase (EC 4.2.99.9) activity; auxotrophs of M. roseus had deficiencies in PAPS reductase, sulfite reductase, or serine transacetylase activity. Results of studies with various mutagens suggested that sulfur amino acid auxotrophy was primarily the result of a single base substitution in usually one or two of the genes controlling biosynthesis. A preliminary study of the amino acid composition of sweat suggested that this important source of nutrients does not contain adequate amounts of cysteine for the growth of cysteine auxotrophs but contains methionine that may be utilized in place of cysteine.", "contents": "Sulfur amino acid auxotrophy in Micrococcus species isolated from human skin. Since methionine and (or) cysteine are required by a large percentage of natural auxotrophic Micrococcus strains isolated from human skin, investigations were directed to determine the specific enzymes affected in sulfur amino acid biosynthesis. Known intermediates in the interrelated cysteine and methionine biosynthetic pathways were tested as growth stimulants. Based on these growth studies, sulfur amino acid auxotrophs were grouped into three cysteine classes and five methionine classes. Selected auxotrophs of M. luteus had deficiencies in ATP sulfurylase (EC 2.7.7.4) and adenosine-5-sulfatophosphate (APS) kinase (EC 2.7.1.25), sulfite reductase (EC 1.8.1.2), serine transacetylase (EC 2.3.1.30), or beta-cystathionase (EC 4.4.1.8) activity; auxotrophs of M. lylae had deficiencies in sulfite reductase and serine transacetylase, beta-cystathionase, or N5, N10-methyltetrahydrofolate reductase (EC 1.1.1.68) activity; all auxotrophs of M. sedentarius tested had deficiencies in N5,N10-methyltetrahydrofolate reductase activity; auxotrophs of M. nishinomiyaensis had deficiencies in adenosine-3-phosphate-5-sulfatophosphate (PAPS) reductase, sulfite reductase, serine transacetylase, or N5,N10-methyltetrahydrofolate reductase activity; auxotrophs of M. varians had deficiencies in APS kinase, PAPS reductase, sulfite reductase, homoserine omicron-transsuccinylase, beta-cystathionase, or N5,N10-methyltetrahydrofolate reductase activity; auxotrophs of M. kristinae had deficiencies in serine transacetylase or cystathionine-gamma-synthase (EC 4.2.99.9) activity; auxotrophs of M. roseus had deficiencies in PAPS reductase, sulfite reductase, or serine transacetylase activity. Results of studies with various mutagens suggested that sulfur amino acid auxotrophy was primarily the result of a single base substitution in usually one or two of the genes controlling biosynthesis. A preliminary study of the amino acid composition of sweat suggested that this important source of nutrients does not contain adequate amounts of cysteine for the growth of cysteine auxotrophs but contains methionine that may be utilized in place of cysteine."}
{"id": "PMID:188533", "title": "Isolation of apparently wild strains of poliovirus type 1 from sewage in the Ottawa area.", "content": "In the first 4 months of 1974, 140 gauze pad samples of sewage collected in the Ottawa area were analysed by the BS-C-1 cell system for the presence of viruses pathogenic for humans. Viruses were isolated from 111 (79%) of the samples. Of the 72 (65%) isolates identified by serology and electron microscopic examination, 56 (78%) were reoviruses and 16 (22%), enteroviruses. The enterovirus isolates included one coxsackievirus B4, one vaccine strain of poliovirus type 3, nine vaccine strains of poliovirus type 1 and five strains of poliovirus type 1 that proved by serodifferentiation and temperature marker tests to be different from vaccine strains. The fact that these strains were present in the community sewage in readily detectable concentrations at a time when immunity against polioviruses is declining in such communities is a cause for concern.", "contents": "Isolation of apparently wild strains of poliovirus type 1 from sewage in the Ottawa area. In the first 4 months of 1974, 140 gauze pad samples of sewage collected in the Ottawa area were analysed by the BS-C-1 cell system for the presence of viruses pathogenic for humans. Viruses were isolated from 111 (79%) of the samples. Of the 72 (65%) isolates identified by serology and electron microscopic examination, 56 (78%) were reoviruses and 16 (22%), enteroviruses. The enterovirus isolates included one coxsackievirus B4, one vaccine strain of poliovirus type 3, nine vaccine strains of poliovirus type 1 and five strains of poliovirus type 1 that proved by serodifferentiation and temperature marker tests to be different from vaccine strains. The fact that these strains were present in the community sewage in readily detectable concentrations at a time when immunity against polioviruses is declining in such communities is a cause for concern."}
{"id": "PMID:188535", "title": "Epithelioid sarcoma: ultrastructural similarity to nodular synovitis.", "content": "The ultrastructure of nodular synovitis of the knee and epithelioid sarcoma of the hand are compared. Both lesions show a similar pattern of light and dark cells having filopodia and microvilli, an outer coat of finely granular matrix without well defined basal laminae, maculae adherentes and attachment sites, pinocytotic vesicles, cytoplasmic filaments and complex nuclear invaginations. These similarities suggest a common histogenesis and support the concept that the epithelioid sarcoma is derived from synovioblastic mesenchyme.", "contents": "Epithelioid sarcoma: ultrastructural similarity to nodular synovitis. The ultrastructure of nodular synovitis of the knee and epithelioid sarcoma of the hand are compared. Both lesions show a similar pattern of light and dark cells having filopodia and microvilli, an outer coat of finely granular matrix without well defined basal laminae, maculae adherentes and attachment sites, pinocytotic vesicles, cytoplasmic filaments and complex nuclear invaginations. These similarities suggest a common histogenesis and support the concept that the epithelioid sarcoma is derived from synovioblastic mesenchyme."}
{"id": "PMID:188536", "title": "Pulmonary blastoma: an ultrastructural study with a brief review of literature and a discussion of pathogenesis.", "content": "A pulmonary blastoma is reported in a 19-year-old black female. The light and electron microscopic characterics are described; they are found to be similar to those of the fetal lung prior to the fourth gestational month. Although the ultrastructural features do not favor any particular theory of histogenesis of this unique tumor, evidence for the commonly held theory that the tumor arises from pluipotential pulmonary blastema seems tenuous. A brief review of the literature disclosed 38 other similar cases. There was a male predominance with an average age of detection at 39 years. Sputum cytology was rarely positive. Among tumors larger than 5 cm in diameter, survival was usually less than 2 years. Metastases were present in approximately half of the cases.", "contents": "Pulmonary blastoma: an ultrastructural study with a brief review of literature and a discussion of pathogenesis. A pulmonary blastoma is reported in a 19-year-old black female. The light and electron microscopic characterics are described; they are found to be similar to those of the fetal lung prior to the fourth gestational month. Although the ultrastructural features do not favor any particular theory of histogenesis of this unique tumor, evidence for the commonly held theory that the tumor arises from pluipotential pulmonary blastema seems tenuous. A brief review of the literature disclosed 38 other similar cases. There was a male predominance with an average age of detection at 39 years. Sputum cytology was rarely positive. Among tumors larger than 5 cm in diameter, survival was usually less than 2 years. Metastases were present in approximately half of the cases."}
{"id": "PMID:188537", "title": "Malignant (fibrous) histiocytoma arising in association with a bone infarct in sicle-cell disease: coincidence or cause-and-effect?", "content": "A patient with homozygous-S sickle-cell disease complicated by malignant (fibrous) histiocytoma arising within a tibial medullary infarct is reported. This is the ninth reported case of human sarcoma associated with bone infarct and the first associated with sickle-cell disease. Evidence for a causal relationship is presented.", "contents": "Malignant (fibrous) histiocytoma arising in association with a bone infarct in sicle-cell disease: coincidence or cause-and-effect? A patient with homozygous-S sickle-cell disease complicated by malignant (fibrous) histiocytoma arising within a tibial medullary infarct is reported. This is the ninth reported case of human sarcoma associated with bone infarct and the first associated with sickle-cell disease. Evidence for a causal relationship is presented."}
{"id": "PMID:188538", "title": "Herpetic esophagitis in patients with cancer: ante mortem diagnosis by brush cytology.", "content": "Ante mortem diagnosis of herpetic esophagitis has been made in four immunosuppressed patients with cancer. The diagnosis was made by brush cytology at the time of esophagoscopy. All four patients had severe dysphagia unresponsive to nystatin therapy and the diagnosis of herpes infection excluded the use of Amphotericin B for resistant moniliasis. The diagnosis of herpes virus infection of the esophagus has been previously made almost exclusively at post mortem examination. Herpetic esophagitis is shown to be not necessarily a preterminal complication in cancer patients. In three of the four patients the esophagitis resolved as the patients responded to anti-tumor therapy.", "contents": "Herpetic esophagitis in patients with cancer: ante mortem diagnosis by brush cytology. Ante mortem diagnosis of herpetic esophagitis has been made in four immunosuppressed patients with cancer. The diagnosis was made by brush cytology at the time of esophagoscopy. All four patients had severe dysphagia unresponsive to nystatin therapy and the diagnosis of herpes infection excluded the use of Amphotericin B for resistant moniliasis. The diagnosis of herpes virus infection of the esophagus has been previously made almost exclusively at post mortem examination. Herpetic esophagitis is shown to be not necessarily a preterminal complication in cancer patients. In three of the four patients the esophagitis resolved as the patients responded to anti-tumor therapy."}
{"id": "PMID:188539", "title": "Morphogenesis of pancreatoblastoma, infantile carcinoma of the pancreas: report of two cases.", "content": "Two cases of infantile carcinoma of the pancreas were diagnosed as pancreatoblastoma based on the morphogenesis of the tumors. These encapsulated tumors adhered to the head of the pancreas and to the descending portion of the duodenum. Histologic examination revealed an organoid structure made up of cords or nodules of squamoid cells with elongated nuclei arranged in a parallel fasciculating pattern (squamoid corpuscles), surrounding tubular structures of columnar epithelial cells and intermediate light cell masses with little differentiation. Electron microscopy revealed zymogen-like granules and well developed granular endoplasmic reticulum in the cytoplasm. There were no detectable islet cells in tumor tissue. Both of these tumors could be derived from the ventral pancreas and be isolated by the lack of communication with the duct of Wirsung. As the duct of Santorini was patent, extirpation of these organoid tumors would not influence secretion of pancreatic juice. Considering the favorable prognosis after extirpation of these tumors, they should be differentiated from the usual adenocarcinoma of the pancreas occurring in adults.", "contents": "Morphogenesis of pancreatoblastoma, infantile carcinoma of the pancreas: report of two cases. Two cases of infantile carcinoma of the pancreas were diagnosed as pancreatoblastoma based on the morphogenesis of the tumors. These encapsulated tumors adhered to the head of the pancreas and to the descending portion of the duodenum. Histologic examination revealed an organoid structure made up of cords or nodules of squamoid cells with elongated nuclei arranged in a parallel fasciculating pattern (squamoid corpuscles), surrounding tubular structures of columnar epithelial cells and intermediate light cell masses with little differentiation. Electron microscopy revealed zymogen-like granules and well developed granular endoplasmic reticulum in the cytoplasm. There were no detectable islet cells in tumor tissue. Both of these tumors could be derived from the ventral pancreas and be isolated by the lack of communication with the duct of Wirsung. As the duct of Santorini was patent, extirpation of these organoid tumors would not influence secretion of pancreatic juice. Considering the favorable prognosis after extirpation of these tumors, they should be differentiated from the usual adenocarcinoma of the pancreas occurring in adults."}
{"id": "PMID:188540", "title": "Adriamycin cardiotoxicity in children: case reports, literature review, and risk factors.", "content": "Two children with Wilms' tumor and prior thoracic radiation developed congestive heart failure at cumulative adriamycin doses of 350 mg/m2 and 400 mg/m2. Details of these two cases and a summary of previously reported adriamycin cardiotoxicity in children are presented. Dose recommendations and predictive tests are discussed.", "contents": "Adriamycin cardiotoxicity in children: case reports, literature review, and risk factors. Two children with Wilms' tumor and prior thoracic radiation developed congestive heart failure at cumulative adriamycin doses of 350 mg/m2 and 400 mg/m2. Details of these two cases and a summary of previously reported adriamycin cardiotoxicity in children are presented. Dose recommendations and predictive tests are discussed."}
{"id": "PMID:188541", "title": "Postlymphographic cerebral lipid embolization in the vena cava superior syndrome.", "content": "A recent case of Lipiodol Ultrafluid embolism to the brain is reported. Pathogenetic concepts involving right-to-left shunts, and lympho-venous shunts with pulmonary capillary overloading are reviewed. In addition, it is suggested that a local disturbance in cerebral circulation due to a cava superior syndrome may contribute to the severe cerebral symptoms.", "contents": "Postlymphographic cerebral lipid embolization in the vena cava superior syndrome. A recent case of Lipiodol Ultrafluid embolism to the brain is reported. Pathogenetic concepts involving right-to-left shunts, and lympho-venous shunts with pulmonary capillary overloading are reviewed. In addition, it is suggested that a local disturbance in cerebral circulation due to a cava superior syndrome may contribute to the severe cerebral symptoms."}
{"id": "PMID:188543", "title": "Interrelationships and functions of the pyruvate kinase isozymes and their variant forms: a review.", "content": "The relationships among and the properties of the pyruvate kinase isozymes are reviewed, emphasizing their potential role in carcinogenesis. Particular consideration is given to evaluation of the concept that the three major nonreadily interconvertible forms are the products of distinct genes, the relationship of these forms to additional separable forms of pyruvate kinase, the types and possible functions of interconvertible forms of the major isozymes, and mechanisms affecting the genetic expression of the isozymes. Emphasis is placed upon the apparent derepression of the fetal isozyme in hepatomas and the influence of neoplasms and their extracts on the expression of pyruvate kinase in the liver of host animals.", "contents": "Interrelationships and functions of the pyruvate kinase isozymes and their variant forms: a review. The relationships among and the properties of the pyruvate kinase isozymes are reviewed, emphasizing their potential role in carcinogenesis. Particular consideration is given to evaluation of the concept that the three major nonreadily interconvertible forms are the products of distinct genes, the relationship of these forms to additional separable forms of pyruvate kinase, the types and possible functions of interconvertible forms of the major isozymes, and mechanisms affecting the genetic expression of the isozymes. Emphasis is placed upon the apparent derepression of the fetal isozyme in hepatomas and the influence of neoplasms and their extracts on the expression of pyruvate kinase in the liver of host animals."}
{"id": "PMID:188544", "title": "Metabolism of [3H]-methylcholanthrene in the perfused rat liver.", "content": "The metabolism of [3H]-3-methylcholanthrene (3-MC) was studied in the isolated, perfused rat liver. Following addition of 250 mug to the perfusion fluid, 3-MC disappeared rapidly. After 2 hr, approximately 34% of the radioactivity was excreted in the bile, 6% remained in the perfusate, and 60% was found in the liver. Of the liver radioactivity, 80% was unchanged 3-MC, 11% was conjugated metabolites, 4% was free hydroxymetabolites, and 4% was nonextractable, presumably bound to macromolecules. Of the perfusate radioactivity, 82% was conjugated metabolites, 3% was free hydroxymetabolites, and 15% was unchanged 3-MG. A similar distribution was observed in intact, bile-cannulated rats, but biliary excretion was about one-fourth as high with double the i.v.-injected dose. Biliary excretion in perfused livers rose rapidly during the first 30 to 40 min, then decreased steadily. It was nearly twice as high in male as in female rat livers. Pretreatment of rats with 3-MC more than doubled the biliary excretion rate over the first 20 to 30 min in livers of both sexes and raised that of the female to that of the male rat liver. Neither retinol acetate nor 7,8-benzoflavone had any appreciable effect on biliary excretion of 3-MC metabolites. 2-Diethylaminoethyl-2,2-diphenylvalerate, a well-known microsomal oxygenase inhibitor, lowered excretion by 80 to 90% and lengthened the lag period, and dibutyryl-3',5'-cyclic adenosine monophosphate markedly increased the rate of excretion of 3-MC metabolites. Fractionation of bile by chromatography on Sephadex LH-20 revealed six well-defined peaks of radioactivity. In contrast, bile of intact rats given 3-MC gave a pattern on Sephadex chromatography consisting of only three peaks. Preliminary data suggest that these consist of conjugates of dihydroxymetabolites as well as more highly hydroxylate derivatives. The data obtained indicate that the perfused liver is an appropriate experimental model for studies on the hepatobiliary metabolism of carcinogens.", "contents": "Metabolism of [3H]-methylcholanthrene in the perfused rat liver. The metabolism of [3H]-3-methylcholanthrene (3-MC) was studied in the isolated, perfused rat liver. Following addition of 250 mug to the perfusion fluid, 3-MC disappeared rapidly. After 2 hr, approximately 34% of the radioactivity was excreted in the bile, 6% remained in the perfusate, and 60% was found in the liver. Of the liver radioactivity, 80% was unchanged 3-MC, 11% was conjugated metabolites, 4% was free hydroxymetabolites, and 4% was nonextractable, presumably bound to macromolecules. Of the perfusate radioactivity, 82% was conjugated metabolites, 3% was free hydroxymetabolites, and 15% was unchanged 3-MG. A similar distribution was observed in intact, bile-cannulated rats, but biliary excretion was about one-fourth as high with double the i.v.-injected dose. Biliary excretion in perfused livers rose rapidly during the first 30 to 40 min, then decreased steadily. It was nearly twice as high in male as in female rat livers. Pretreatment of rats with 3-MC more than doubled the biliary excretion rate over the first 20 to 30 min in livers of both sexes and raised that of the female to that of the male rat liver. Neither retinol acetate nor 7,8-benzoflavone had any appreciable effect on biliary excretion of 3-MC metabolites. 2-Diethylaminoethyl-2,2-diphenylvalerate, a well-known microsomal oxygenase inhibitor, lowered excretion by 80 to 90% and lengthened the lag period, and dibutyryl-3',5'-cyclic adenosine monophosphate markedly increased the rate of excretion of 3-MC metabolites. Fractionation of bile by chromatography on Sephadex LH-20 revealed six well-defined peaks of radioactivity. In contrast, bile of intact rats given 3-MC gave a pattern on Sephadex chromatography consisting of only three peaks. Preliminary data suggest that these consist of conjugates of dihydroxymetabolites as well as more highly hydroxylate derivatives. The data obtained indicate that the perfused liver is an appropriate experimental model for studies on the hepatobiliary metabolism of carcinogens."}
{"id": "PMID:188545", "title": "Purine metabolic cycle in normal and leukemic leukocytes.", "content": "Purine metabolism and reutilization pathways were studied as they applied to normal and leukemic leukocytes. The enzyme activities were expressed in terms of the quantity of protein extracted and per 10(10) cells. Whereas the protein extracted and the enzyme activities from normal lymphocytes were relatively constant, considerable variation was noted in cases of chronic lymphocytic leukemia (CLL). This variability in the properties of the leukemic cells suggests that the difference may be useful in the subclassification of the leukemias. The studies of the complete enzyme system were done with 300 million cells. The extraction of 350,000 normal lymphocytes/mul gave a soluble protein concentration of 1.46+/-0.16 mg protein per ml, and the yield from the same number of CLL lymphocytes varied between 0.72 and 8.32 mg protein per ml. The 5'-nucleotidase activity gave an inverse correlation with the amount of extractable protein. In individual cases of CLL, the protein concentrations and the 5'-nucleotidase activities were found on either side of the normal values. In most cases, the adenosine deaminase of CLL lymphocytic cell extracts was lower than normal, and the adenosine kinase was higher; in the CLL cells, these two enzymes gave a positive correlation with one another. Little or no difference was observed in the activities of the purine nucleoside phosphorylases in extracts of normal or leukemic lymphocytes and granulocytes. The hypoxanthine-guanine and adenine phosphoribosyltransferase activities increased in the leukemic granulocytes but almost always showed a decrease in the CLL lymphocytes when compared with the normal cells. Most of the leukemic cells had greater than normal activities of the enzymes synthesizing phosphoribosyl pyrophosphate when tested with the purines. The total nucleotide produced from adenine and guanine with adenine- and hypoxanthine-guanine phosphoribosyltransferase was about equal in normal and leukemic lymphocytes, but the proportion of the adenosine 5'-triphosphate in the product was much greater with the leukemic cells. This suggested that the ribosyltransferase activities were the same in both types of cells, but the nucleoside kinases and the nucleoside diphosphate kinases were more active in the leukemic cells. Inosine monophosphate dehydrogenase was less active than normal in the CLL cell extracts and was not directly related to the amount of inosine monophosphate generated from hypoxanthine.", "contents": "Purine metabolic cycle in normal and leukemic leukocytes. Purine metabolism and reutilization pathways were studied as they applied to normal and leukemic leukocytes. The enzyme activities were expressed in terms of the quantity of protein extracted and per 10(10) cells. Whereas the protein extracted and the enzyme activities from normal lymphocytes were relatively constant, considerable variation was noted in cases of chronic lymphocytic leukemia (CLL). This variability in the properties of the leukemic cells suggests that the difference may be useful in the subclassification of the leukemias. The studies of the complete enzyme system were done with 300 million cells. The extraction of 350,000 normal lymphocytes/mul gave a soluble protein concentration of 1.46+/-0.16 mg protein per ml, and the yield from the same number of CLL lymphocytes varied between 0.72 and 8.32 mg protein per ml. The 5'-nucleotidase activity gave an inverse correlation with the amount of extractable protein. In individual cases of CLL, the protein concentrations and the 5'-nucleotidase activities were found on either side of the normal values. In most cases, the adenosine deaminase of CLL lymphocytic cell extracts was lower than normal, and the adenosine kinase was higher; in the CLL cells, these two enzymes gave a positive correlation with one another. Little or no difference was observed in the activities of the purine nucleoside phosphorylases in extracts of normal or leukemic lymphocytes and granulocytes. The hypoxanthine-guanine and adenine phosphoribosyltransferase activities increased in the leukemic granulocytes but almost always showed a decrease in the CLL lymphocytes when compared with the normal cells. Most of the leukemic cells had greater than normal activities of the enzymes synthesizing phosphoribosyl pyrophosphate when tested with the purines. The total nucleotide produced from adenine and guanine with adenine- and hypoxanthine-guanine phosphoribosyltransferase was about equal in normal and leukemic lymphocytes, but the proportion of the adenosine 5'-triphosphate in the product was much greater with the leukemic cells. This suggested that the ribosyltransferase activities were the same in both types of cells, but the nucleoside kinases and the nucleoside diphosphate kinases were more active in the leukemic cells. Inosine monophosphate dehydrogenase was less active than normal in the CLL cell extracts and was not directly related to the amount of inosine monophosphate generated from hypoxanthine."}
{"id": "PMID:188546", "title": "Partial purification and characterization of tumor and liver S-adenosylmethionine synthetases.", "content": "The S-adenosylmethionine synthetase activities of rat liver and Novikoff ascites tumor have been partially purified and characterized by chromatographic behavior, kinetic analysis, sulfhydryl dependency, and response to inhibitors. We have shown that the tumor contains a single form of the enzyme, with a Km (methionine) of 21 muM, and that the liver contains two isofunctional forms, a minor form with a Km (methionine) of 21 muM, as well as a major form with a Km of 1 mM. The tumor contained more of the low Km form of the enzyme than the liver, although the total enzyme activity of liver (measured at high substrate concentrations) exceeded that of the tumor severalfold. The tumor enzyme also corresponded to the minor form of liver enzyme in elution position from Sephadex G-150 and diethylamino-ethyl cellulose, and both had a Km (adenosine 5'-triphosphate) of 0.14 mM. The tumor enzyme differed from the major form of the liver enzymes in elution position, and the Km (adenosine 5'-triphosphate) for the latter was 1.5 mM. In contrast to the major liver enzyme, the tumor enzyme did not appear to require sulfhydryl agents for the activity to be detected, was inhibited by S-adenosylmethionine, and was inhibited to a greater degree by tripolyphosphate. It is suggested that the two forms of the enzyme are involved in the production of S-adenosylmethionine for different biological functions, and their different properties may allow selective inhibition of tumor growth by chemotherapeutic agents.", "contents": "Partial purification and characterization of tumor and liver S-adenosylmethionine synthetases. The S-adenosylmethionine synthetase activities of rat liver and Novikoff ascites tumor have been partially purified and characterized by chromatographic behavior, kinetic analysis, sulfhydryl dependency, and response to inhibitors. We have shown that the tumor contains a single form of the enzyme, with a Km (methionine) of 21 muM, and that the liver contains two isofunctional forms, a minor form with a Km (methionine) of 21 muM, as well as a major form with a Km of 1 mM. The tumor contained more of the low Km form of the enzyme than the liver, although the total enzyme activity of liver (measured at high substrate concentrations) exceeded that of the tumor severalfold. The tumor enzyme also corresponded to the minor form of liver enzyme in elution position from Sephadex G-150 and diethylamino-ethyl cellulose, and both had a Km (adenosine 5'-triphosphate) of 0.14 mM. The tumor enzyme differed from the major form of the liver enzymes in elution position, and the Km (adenosine 5'-triphosphate) for the latter was 1.5 mM. In contrast to the major liver enzyme, the tumor enzyme did not appear to require sulfhydryl agents for the activity to be detected, was inhibited by S-adenosylmethionine, and was inhibited to a greater degree by tripolyphosphate. It is suggested that the two forms of the enzyme are involved in the production of S-adenosylmethionine for different biological functions, and their different properties may allow selective inhibition of tumor growth by chemotherapeutic agents."}
{"id": "PMID:188547", "title": "3-methylcholanthrene-induced monooxygenase (O-deethylation) activity of human lymphocytes.", "content": "With a direct fluorescence assay, the levels of mixed-function oxidase activity were determined in mitogen-activated human lymphocytes. The O-deethylation of ethoxyresorufin to resorufin was used to quantitate mixed-function oxidase activity. Ethoxyresorufin O-deethylase activity was low to nondetectable in noninduced, mitogen-activated cells, but it was readily detected in 3-methylcholanthrene, mitogen-activated lymphocytes. The activity was: (a) dependent on assay time and number of lymphocytes; (b) dependent on the presence of reduced nicotinamide adenine dinucleotide phosphate; (c) stable to freezing at -80 degrees for at least 2 weeks; (d) reproducibly detected in duplicate samples of blood from one individual when cultured and assayed at the same time; but (e) quite variable in samples of blood from one individual at different times. Since in hepatic and pulmonary tissue of model animal systems ethoxyresorufin is a specific substrate for cytochrome P-448-associated monooxygenases, the use of this chemical could proffer an assay that specifically measures human cytochrome P-448-associated activity.", "contents": "3-methylcholanthrene-induced monooxygenase (O-deethylation) activity of human lymphocytes. With a direct fluorescence assay, the levels of mixed-function oxidase activity were determined in mitogen-activated human lymphocytes. The O-deethylation of ethoxyresorufin to resorufin was used to quantitate mixed-function oxidase activity. Ethoxyresorufin O-deethylase activity was low to nondetectable in noninduced, mitogen-activated cells, but it was readily detected in 3-methylcholanthrene, mitogen-activated lymphocytes. The activity was: (a) dependent on assay time and number of lymphocytes; (b) dependent on the presence of reduced nicotinamide adenine dinucleotide phosphate; (c) stable to freezing at -80 degrees for at least 2 weeks; (d) reproducibly detected in duplicate samples of blood from one individual when cultured and assayed at the same time; but (e) quite variable in samples of blood from one individual at different times. Since in hepatic and pulmonary tissue of model animal systems ethoxyresorufin is a specific substrate for cytochrome P-448-associated monooxygenases, the use of this chemical could proffer an assay that specifically measures human cytochrome P-448-associated activity."}
{"id": "PMID:188548", "title": "Metabolic regulation and relationship of endogenous protein kinase activity and steroidogenesis in isolated adrenocortical carcinoma cells of the rat.", "content": "In the adrenocortical carcinoma cell, in contrast to normal isolated adrenal cells, 10 to 50 muunits of ACTH do not raise the level of adenosine cyclic 3':5'-monophosphate (cyclic AMP), protein kinase activity, and steroidogenesis. This indicates a lesion in the tumor adenylate cyclase system. Two-tenths to 10 mM cyclic AMP and guanosine cyclic 3':5'-monophosphate (cyclic GMP) which stimulate steroidogenesis in a normal cell, activate protein kinase activity in a concentration-response manner without any detectable rise in steroidogenesis in the adrenocortical carcinoma cell. Cycloheximide and actinomycin D do not inhibit the stimulation of the phosphorylation. These results suggest that the tumor cyclic nucleotide-dependent protein kinase activity is unrelated to steroidogenesis and is also not under the transcriptional or translational control steps. Curiously, muM concentrations of cyclic AMP, in contrast to cyclic GMP, stimulate protein kinase activity. In a normal cell, both cyclic AMP and cyclic GMP, in this concentration range, stimulate protein kinase without an increase in steroidogenesis. It is therefore proposed that, in contrast to the normal cell, there is an additional defect in cyclic GMP-dependent protein kinase.", "contents": "Metabolic regulation and relationship of endogenous protein kinase activity and steroidogenesis in isolated adrenocortical carcinoma cells of the rat. In the adrenocortical carcinoma cell, in contrast to normal isolated adrenal cells, 10 to 50 muunits of ACTH do not raise the level of adenosine cyclic 3':5'-monophosphate (cyclic AMP), protein kinase activity, and steroidogenesis. This indicates a lesion in the tumor adenylate cyclase system. Two-tenths to 10 mM cyclic AMP and guanosine cyclic 3':5'-monophosphate (cyclic GMP) which stimulate steroidogenesis in a normal cell, activate protein kinase activity in a concentration-response manner without any detectable rise in steroidogenesis in the adrenocortical carcinoma cell. Cycloheximide and actinomycin D do not inhibit the stimulation of the phosphorylation. These results suggest that the tumor cyclic nucleotide-dependent protein kinase activity is unrelated to steroidogenesis and is also not under the transcriptional or translational control steps. Curiously, muM concentrations of cyclic AMP, in contrast to cyclic GMP, stimulate protein kinase activity. In a normal cell, both cyclic AMP and cyclic GMP, in this concentration range, stimulate protein kinase without an increase in steroidogenesis. It is therefore proposed that, in contrast to the normal cell, there is an additional defect in cyclic GMP-dependent protein kinase."}
{"id": "PMID:188549", "title": "Different survival of normal and transformed cells exposed to nutritional conditions nonpermissive for growth.", "content": "When human diploid fibroblasts (WI-38 cells) in culture are maintained under conditions nonpermissive for growth (serum restriction), cell proliferation ceases but the cells remain viable for extended periods of time. Under similar restrictive conditions nonpermissive for growth. SV-40-transformed WI-38 fibroblasts (2RA cells) die off at a rate of 10% per day. In resting WI-38 cells, the template activity of isolated nuclei is related to both cell density and the length of time the cells have been quiescent. In 2RA cells, nuclear template activity is related to time after plating, regardless of cell density. The results are compatible with the hypothesis that normal cells can enter a G0 state more easily than transformed cells. This, in turn, would allow normal cells to survive under conditions nonpermissive for growth, whereas transformed cells gradually die off.", "contents": "Different survival of normal and transformed cells exposed to nutritional conditions nonpermissive for growth. When human diploid fibroblasts (WI-38 cells) in culture are maintained under conditions nonpermissive for growth (serum restriction), cell proliferation ceases but the cells remain viable for extended periods of time. Under similar restrictive conditions nonpermissive for growth. SV-40-transformed WI-38 fibroblasts (2RA cells) die off at a rate of 10% per day. In resting WI-38 cells, the template activity of isolated nuclei is related to both cell density and the length of time the cells have been quiescent. In 2RA cells, nuclear template activity is related to time after plating, regardless of cell density. The results are compatible with the hypothesis that normal cells can enter a G0 state more easily than transformed cells. This, in turn, would allow normal cells to survive under conditions nonpermissive for growth, whereas transformed cells gradually die off."}
{"id": "PMID:188550", "title": "Mitochondrial and microsomal phospholipids of Morris hepatoma 7777.", "content": "The phospholipids of both mitochondrial and microsomal membranes from normal liver, host liver, and Morris hepatoma 7777 were isolated, separated, and quantitated. The total as well as the individual fatty acid concentrations and compositions were determined. The total phosphlipids isolated from tumor mitochondria were idly altered, compared with mitochondria from other normal or host liver. The polyenoic acids were decreased, and there was a concomitant increase in the monoenes. When the respiratory control was determined, the tumor mitochondria exhibited a significant decrease in this parameter. The tumor microsomal membrane fraction, on the other hand, contained about 50% less phospholipid than the controls. The fatty acid patterns of the total as well as the individual phospholipids were quite similar to those observed in the mitochondria. The species of phosphatidylcholine from both membrane fractions were separated by argentation chromatography of the intact molecules, and, as predicted by the fatty acid compositions, the major species of the tumor was the monoenoic/dienoic fraction. The acyl coenzyme A:1-acyl glycerophosphorylcholine acyltransferases, which aid in controlling the fatty acid composition of phospholipids, were measured. The very marked increase in activity of these enzymes toward polyenoic as well as monoenic fatty acids suggested that the polyenoic acids were not available for use in the resynthesis of the phosphatidylcholines in the tumor.", "contents": "Mitochondrial and microsomal phospholipids of Morris hepatoma 7777. The phospholipids of both mitochondrial and microsomal membranes from normal liver, host liver, and Morris hepatoma 7777 were isolated, separated, and quantitated. The total as well as the individual fatty acid concentrations and compositions were determined. The total phosphlipids isolated from tumor mitochondria were idly altered, compared with mitochondria from other normal or host liver. The polyenoic acids were decreased, and there was a concomitant increase in the monoenes. When the respiratory control was determined, the tumor mitochondria exhibited a significant decrease in this parameter. The tumor microsomal membrane fraction, on the other hand, contained about 50% less phospholipid than the controls. The fatty acid patterns of the total as well as the individual phospholipids were quite similar to those observed in the mitochondria. The species of phosphatidylcholine from both membrane fractions were separated by argentation chromatography of the intact molecules, and, as predicted by the fatty acid compositions, the major species of the tumor was the monoenoic/dienoic fraction. The acyl coenzyme A:1-acyl glycerophosphorylcholine acyltransferases, which aid in controlling the fatty acid composition of phospholipids, were measured. The very marked increase in activity of these enzymes toward polyenoic as well as monoenic fatty acids suggested that the polyenoic acids were not available for use in the resynthesis of the phosphatidylcholines in the tumor."}
{"id": "PMID:188551", "title": "Prolactin binding to R3230AC mammary carcinoma and liver in hormone-treated and diabetic rats.", "content": "Specific 125I-labeled prolactin binding was measured in membrane particles prepared from R3230AC mammary carcinoma and liver of tumor-bearing Fischer rats after either prolactin, estrogen, or lergotrile mesylate treatment, or after the induction of diabetes by streptozotocin. Hormone binding to tumors was decreased by treatment with prolactin (0.5 or 1 mg/day) or estradiol valerate (7.5 mg/kg/week). In contrast, prolactin treatment did not affect prolactin binding to liver membrane particles, but estradiol valerate treatment resulted in a four-fold increase in prolactin binding to this tissue. Lergotrile mesylate, which lowers plasma prolactin levels, did not affect tumor growth or prolactin binding to either tumor or liver. Prolactin binding to both tumor and liver was significantly reduced in diabetic rats, suggesting that insulin may play an important role in controlling tissue sensitivity to prolactin. Specific binding of 125I-labeled prolactin to enzymatically dissociated cells from R3230AC tumors was demonstrated in vitro. The binding capacity of the cells was found to be of the same order of magnitude as the binding capacity in membrane preparations when appropriate corrections were applied for yields of cells and membranes. R3230AC tumor, which is responsive to prolactin appears therefore to be a useful model system for further study aimed at elucidation of growth and metabolic response to the hormone prolactin in breast cancer.", "contents": "Prolactin binding to R3230AC mammary carcinoma and liver in hormone-treated and diabetic rats. Specific 125I-labeled prolactin binding was measured in membrane particles prepared from R3230AC mammary carcinoma and liver of tumor-bearing Fischer rats after either prolactin, estrogen, or lergotrile mesylate treatment, or after the induction of diabetes by streptozotocin. Hormone binding to tumors was decreased by treatment with prolactin (0.5 or 1 mg/day) or estradiol valerate (7.5 mg/kg/week). In contrast, prolactin treatment did not affect prolactin binding to liver membrane particles, but estradiol valerate treatment resulted in a four-fold increase in prolactin binding to this tissue. Lergotrile mesylate, which lowers plasma prolactin levels, did not affect tumor growth or prolactin binding to either tumor or liver. Prolactin binding to both tumor and liver was significantly reduced in diabetic rats, suggesting that insulin may play an important role in controlling tissue sensitivity to prolactin. Specific binding of 125I-labeled prolactin to enzymatically dissociated cells from R3230AC tumors was demonstrated in vitro. The binding capacity of the cells was found to be of the same order of magnitude as the binding capacity in membrane preparations when appropriate corrections were applied for yields of cells and membranes. R3230AC tumor, which is responsive to prolactin appears therefore to be a useful model system for further study aimed at elucidation of growth and metabolic response to the hormone prolactin in breast cancer."}
{"id": "PMID:188552", "title": "Enzyme pattern-directed chemotherapy: synergistic interaction of 3-deazauridine with D-galactosamine.", "content": "We tested an experimental approach in which the specialized enzymatic pattern characteristic of the tissue of origin of a tumor might be exploited to target and enhance drug selectivity. In the present work, the D-galactosamine-induced depletion of uridine 5'-triphosphate (primarily a hepatic event) was employed to enhance the growth inhibition caused by 3-deazauridine. As predicted, the drug effect was most pronounced in the slower growing, well differentiated hepatoma lines where the activities of certain hepatic metabolic pathways and enzymes, though decreased, were still operative. The interactions of D-galactosamine and cytosine arabinoside with 3-deazauridine were examined in vitro in four liver tumor cell lines and two nonhepatic lines. The effects of D-galactosamine and 3-deazauridine on the growth of the Morris hepatoma cell lines 3924A, 8999S,AND 8999R were strongly synergistic; on the Novikoff hepatoma and the nonhepatic cell lines they were only additive. The combination of 3-deazauridine with cytosine arabinoside gave approximately additive growth inhibition with all cell types, without selective toxicity towards the hepatocellular lines. Results of growth-inhibition studies with the combination of D-galactosamine and cytosine arabinoside and with combinations of all three agents are also presented. These results are analyzed in the context of the regulation of hepatic pyrimidine nucleotide metabolism and our design of enzyme pattern directed drug selectivity.", "contents": "Enzyme pattern-directed chemotherapy: synergistic interaction of 3-deazauridine with D-galactosamine. We tested an experimental approach in which the specialized enzymatic pattern characteristic of the tissue of origin of a tumor might be exploited to target and enhance drug selectivity. In the present work, the D-galactosamine-induced depletion of uridine 5'-triphosphate (primarily a hepatic event) was employed to enhance the growth inhibition caused by 3-deazauridine. As predicted, the drug effect was most pronounced in the slower growing, well differentiated hepatoma lines where the activities of certain hepatic metabolic pathways and enzymes, though decreased, were still operative. The interactions of D-galactosamine and cytosine arabinoside with 3-deazauridine were examined in vitro in four liver tumor cell lines and two nonhepatic lines. The effects of D-galactosamine and 3-deazauridine on the growth of the Morris hepatoma cell lines 3924A, 8999S,AND 8999R were strongly synergistic; on the Novikoff hepatoma and the nonhepatic cell lines they were only additive. The combination of 3-deazauridine with cytosine arabinoside gave approximately additive growth inhibition with all cell types, without selective toxicity towards the hepatocellular lines. Results of growth-inhibition studies with the combination of D-galactosamine and cytosine arabinoside and with combinations of all three agents are also presented. These results are analyzed in the context of the regulation of hepatic pyrimidine nucleotide metabolism and our design of enzyme pattern directed drug selectivity."}
{"id": "PMID:188553", "title": "Ca++-induced fusion of proteoliposomes: dependence on transmembrane osmotic gradient.", "content": "The fusion of cytochrome oxidase liposomes with liposomes reconstituted with mitochondrial hydrophobic protein is dependent on the presence of an acidic phospholipid in the liposomes and on the addition of Ca++ions. Liposomes which have grown, by fusion, to diameters in excess of 1000 A lose the ability to fuse further, unless an osmotic gradient across the liposome membrane is established, with the internal osmotic pressure higher than the external. At a given Ca++ concentration, the extent to which this second fusion step takes place is determined by the ratio of internal to external osmolarity. Single-walled liposomes with diameters exceeding 1 mumM have been produced by this technique. The data suggest that the thermodynamic driving force for the Ca++-induced fusion is an excess surface free energy which can be supplied by membrane curvature or transmembrane osmotic gradients.", "contents": "Ca++-induced fusion of proteoliposomes: dependence on transmembrane osmotic gradient. The fusion of cytochrome oxidase liposomes with liposomes reconstituted with mitochondrial hydrophobic protein is dependent on the presence of an acidic phospholipid in the liposomes and on the addition of Ca++ions. Liposomes which have grown, by fusion, to diameters in excess of 1000 A lose the ability to fuse further, unless an osmotic gradient across the liposome membrane is established, with the internal osmotic pressure higher than the external. At a given Ca++ concentration, the extent to which this second fusion step takes place is determined by the ratio of internal to external osmolarity. Single-walled liposomes with diameters exceeding 1 mumM have been produced by this technique. The data suggest that the thermodynamic driving force for the Ca++-induced fusion is an excess surface free energy which can be supplied by membrane curvature or transmembrane osmotic gradients."}
{"id": "PMID:188558", "title": "Cholestane spin label study of filipin action on lipid planar multibilayers.", "content": "EPR spectra of a cholestane probe dissolved in egg yolk lecithin and lecithin-cholesterol planar multibilayers were observed as a function of the filipin dose. The probe is structurally similar to cholesterol; its normal position when dissolved is with the long axis approximately along the bilayer normal. Both cholesterol-containing and cholesterol-free samples showed spectral components characteristic of bilayer fragmentation (tilted domains) which increased with dose. Furthermore, the cholesterol-free spectra indicated that some of the probe was frozen with the long molecular axis perpendicular to the slide normal. The frozen spectral component increased with dose. Spectra from a fatty acid probe did not have this feature. We interpret this as due to probe complexed with filipin (in place of cholesterol) in accordance with the filipin-cholesterol aggregate model of deKruijff and Demel. An ultraviolet study of filipin-probe interaction indicates that the probe is capable of complexing in just such a manner but has less affinity for the drug than cholesterol. Spectra from the cholesttane probe in liposomes were also observed.", "contents": "Cholestane spin label study of filipin action on lipid planar multibilayers. EPR spectra of a cholestane probe dissolved in egg yolk lecithin and lecithin-cholesterol planar multibilayers were observed as a function of the filipin dose. The probe is structurally similar to cholesterol; its normal position when dissolved is with the long axis approximately along the bilayer normal. Both cholesterol-containing and cholesterol-free samples showed spectral components characteristic of bilayer fragmentation (tilted domains) which increased with dose. Furthermore, the cholesterol-free spectra indicated that some of the probe was frozen with the long molecular axis perpendicular to the slide normal. The frozen spectral component increased with dose. Spectra from a fatty acid probe did not have this feature. We interpret this as due to probe complexed with filipin (in place of cholesterol) in accordance with the filipin-cholesterol aggregate model of deKruijff and Demel. An ultraviolet study of filipin-probe interaction indicates that the probe is capable of complexing in just such a manner but has less affinity for the drug than cholesterol. Spectra from the cholesttane probe in liposomes were also observed."}
{"id": "PMID:188559", "title": "Concurrent smallpox and chickenpox.", "content": "Three patients showing smallpox- and chickenpox-like lesions simultaneously were investigated virologically. Both infections were confirmed in the laboratory and, in one case, by electron microscopy.", "contents": "Concurrent smallpox and chickenpox. Three patients showing smallpox- and chickenpox-like lesions simultaneously were investigated virologically. Both infections were confirmed in the laboratory and, in one case, by electron microscopy."}
{"id": "PMID:188563", "title": "[High poly A content of the native genome of murine oncornaviruses : presence of 65-70 S RNA lacking polyadenylic sequences].", "content": "High molecular weight Poly (A) minus RNA was isolated from native genome of murine oncornaviruses. The Poly (A) content of viral genomes seems to depend more on cellular multiplication than viral maturation.", "contents": "[High poly A content of the native genome of murine oncornaviruses : presence of 65-70 S RNA lacking polyadenylic sequences]. High molecular weight Poly (A) minus RNA was isolated from native genome of murine oncornaviruses. The Poly (A) content of viral genomes seems to depend more on cellular multiplication than viral maturation."}
{"id": "PMID:188564", "title": "Two-dimensional immunoelectrophrophoretic pattern of low- and very-low-density lipoproteins, with particular reference to Fredrickson's type III.", "content": "I report the pattern of low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) as revealed by two-dimensional (crossed) immunoelectrophoresis in hyperlipoproteinemia types, II, III, and IV, preliminarily diagnosed by means of a complex lipoprotein profile examination. The higher affinity of Oil Red stain for VLDL- than for LDL-immunoprecipitation zones is peculiar to this lipoprotein class, and crossed immunoelectrophoretograms may thus be helpful for laboratory diagnosis of types IIb and IV in problematic cases. The position and the medium affinity for Oil Red of \"broad beta\" zones appearing in immunoelectrophoretograms of type III hyperlipoproteinemia are suggested as useful criteria for the diagnosis of this condition. From the structural and staining characteristics of VLDL-immunoprecipitation zones, alteration of both composition and antigenic properties of VLDL in hyperlipoproteinemias IIb-IV is deduced. I present in detail the procedure for crossed immunoelectrophoresis as well as that for the lipoprotein profile examination used in this study.", "contents": "Two-dimensional immunoelectrophrophoretic pattern of low- and very-low-density lipoproteins, with particular reference to Fredrickson's type III. I report the pattern of low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) as revealed by two-dimensional (crossed) immunoelectrophoresis in hyperlipoproteinemia types, II, III, and IV, preliminarily diagnosed by means of a complex lipoprotein profile examination. The higher affinity of Oil Red stain for VLDL- than for LDL-immunoprecipitation zones is peculiar to this lipoprotein class, and crossed immunoelectrophoretograms may thus be helpful for laboratory diagnosis of types IIb and IV in problematic cases. The position and the medium affinity for Oil Red of \"broad beta\" zones appearing in immunoelectrophoretograms of type III hyperlipoproteinemia are suggested as useful criteria for the diagnosis of this condition. From the structural and staining characteristics of VLDL-immunoprecipitation zones, alteration of both composition and antigenic properties of VLDL in hyperlipoproteinemias IIb-IV is deduced. I present in detail the procedure for crossed immunoelectrophoresis as well as that for the lipoprotein profile examination used in this study."}
{"id": "PMID:188565", "title": "Interconverting measurements of human lactate dehydrogenase activities in three buffers.", "content": "The lactate-to-pyruvate reaction for serum lactate dehydrogenase (LD) is most frequently assayed in one of three buffers, pyrophosphate (PPi), tris(hydroxymethyl)amino-methane (Tris), or 2-amino-2-methyl-1-propanol (AMP). We described interconverting results for serum samples and for highly purified LD isoenzymes I (dissolved in one of these matrixes) assayed in these buffers under optimized reaction conditions. The equation for converting results obtained for sera in Tris (x) to those in PPi(y) (both at 30 degrees C) is y = 0.74x+10 (n = 98). Since AMP is used extensively in Technicon procedures, we determined the LD activity of sera with an SMA 12/60, at 37 degrees C. The equation for convering these AMP results to results obtained in PPi at 30 degrees C is y = 0.45x-16 (n = 90). Very different equations were obtained with highly purified LD isoenzyme I maintained in two different matrixes and with both isoenzymes assayed in the same matrix. The matrix in which LD is dissolved and the proportion of various LD isoenzymes affect the magnitude of difference in observed LD activity under various conditions. Therefore, in clinical laboratories that use more than one analytical method or when conversion equations are used in the comparison of interlaboratory results, it is important to define the LD source, isoenzyme content, and the matrix, as well as the reaction conditions, and to use many samples with a wide range of activities when determining the conversion equations. For any changes in reagent source, substrate concentration, or alteration in procedure, a new normal range and new conversion equations should be determined.", "contents": "Interconverting measurements of human lactate dehydrogenase activities in three buffers. The lactate-to-pyruvate reaction for serum lactate dehydrogenase (LD) is most frequently assayed in one of three buffers, pyrophosphate (PPi), tris(hydroxymethyl)amino-methane (Tris), or 2-amino-2-methyl-1-propanol (AMP). We described interconverting results for serum samples and for highly purified LD isoenzymes I (dissolved in one of these matrixes) assayed in these buffers under optimized reaction conditions. The equation for converting results obtained for sera in Tris (x) to those in PPi(y) (both at 30 degrees C) is y = 0.74x+10 (n = 98). Since AMP is used extensively in Technicon procedures, we determined the LD activity of sera with an SMA 12/60, at 37 degrees C. The equation for convering these AMP results to results obtained in PPi at 30 degrees C is y = 0.45x-16 (n = 90). Very different equations were obtained with highly purified LD isoenzyme I maintained in two different matrixes and with both isoenzymes assayed in the same matrix. The matrix in which LD is dissolved and the proportion of various LD isoenzymes affect the magnitude of difference in observed LD activity under various conditions. Therefore, in clinical laboratories that use more than one analytical method or when conversion equations are used in the comparison of interlaboratory results, it is important to define the LD source, isoenzyme content, and the matrix, as well as the reaction conditions, and to use many samples with a wide range of activities when determining the conversion equations. For any changes in reagent source, substrate concentration, or alteration in procedure, a new normal range and new conversion equations should be determined."}
{"id": "PMID:188566", "title": "Elevated serum and spleen angiotensin converting enzyme and serum lysozyme in Gaucher's disease.", "content": "In adult chronic non-neuronopathic (Type 1) Gaucher's disease significant (p less than 0.001) elevations of angiotensin converting enzyme in serum (93.3 +/- 14.8 nmol/min/ml; number elevated, 8/11; normal control 32.2 +/- 1.30, n = 58) and spleen (5.62 +/- 0.35 nmol/min/mg protein, n = 2; control, 0.431 +/- 0.101, n = 4) and serum lysozyme (15.6 +/- 3.37 mug/ml; number elevated, 4/5) were observed. The KM for hippuryl-L-histidyl-L-leucine of Gaucher (1.31 mM) and normal (1.23 mM) serum angiotensin converting enzyme were similar. The increased angiotensin converting enzyme (ACE) in Gaucher's disease may be related to the genetic defect resulting in increased ACE synthesis in Gaucher cells, or perhaps generally, while high lysozyme may reflect an increased body mass of reticuloendothelial cells. These enzyme elevations may be of use in suggesting the possible presence of Gaucher's disease and perhaps in assessing the magnitude of pathologic involvement.", "contents": "Elevated serum and spleen angiotensin converting enzyme and serum lysozyme in Gaucher's disease. In adult chronic non-neuronopathic (Type 1) Gaucher's disease significant (p less than 0.001) elevations of angiotensin converting enzyme in serum (93.3 +/- 14.8 nmol/min/ml; number elevated, 8/11; normal control 32.2 +/- 1.30, n = 58) and spleen (5.62 +/- 0.35 nmol/min/mg protein, n = 2; control, 0.431 +/- 0.101, n = 4) and serum lysozyme (15.6 +/- 3.37 mug/ml; number elevated, 4/5) were observed. The KM for hippuryl-L-histidyl-L-leucine of Gaucher (1.31 mM) and normal (1.23 mM) serum angiotensin converting enzyme were similar. The increased angiotensin converting enzyme (ACE) in Gaucher's disease may be related to the genetic defect resulting in increased ACE synthesis in Gaucher cells, or perhaps generally, while high lysozyme may reflect an increased body mass of reticuloendothelial cells. These enzyme elevations may be of use in suggesting the possible presence of Gaucher's disease and perhaps in assessing the magnitude of pathologic involvement."}
{"id": "PMID:188567", "title": "[A simple method for the separation and purification of the surface antigen of hepatitis B from serum (author's transl)].", "content": "The present report describes a simple, rapid and reproducible procedure for preparation of hepatitis B surface antigen from human positive sera, with a satisfactory yield. After removal of beta- and alpha-lipoproteins by dextran sulphate precipitation and subsequent removal of IgM and a part of the other serum proteins by dialysis against distilled water, the supernatant obtained presents almost no change in its surface antigen content. After passing this solution through a molecular sieve of Biogel A-5 m, the surface antigen is detected in a well-defined peak. The fraction correspinding to this peak is collected in its totality. After lyophilization, it is passed through a molecular sieve of CPG 10, in phosphate buffer; this allows recovery of a substance which has retained its structural as well as its antigenic properties, and which is intact and practically free of any serum contamination.", "contents": "[A simple method for the separation and purification of the surface antigen of hepatitis B from serum (author's transl)]. The present report describes a simple, rapid and reproducible procedure for preparation of hepatitis B surface antigen from human positive sera, with a satisfactory yield. After removal of beta- and alpha-lipoproteins by dextran sulphate precipitation and subsequent removal of IgM and a part of the other serum proteins by dialysis against distilled water, the supernatant obtained presents almost no change in its surface antigen content. After passing this solution through a molecular sieve of Biogel A-5 m, the surface antigen is detected in a well-defined peak. The fraction correspinding to this peak is collected in its totality. After lyophilization, it is passed through a molecular sieve of CPG 10, in phosphate buffer; this allows recovery of a substance which has retained its structural as well as its antigenic properties, and which is intact and practically free of any serum contamination."}
{"id": "PMID:188568", "title": "Comparison of whole plasma and perchloric acid-extracted plasma assays for carcinoembryonic antigen.", "content": "A direct, paired, comparison was made of two plasma radioimmunoassays for carcinoembryonic antigen (CEA), between a perchloric acid-extracted, ammonium sulphate precipitation method; and a whole-plasma, double-antibody method. For both assays the same preparations of standard CEA, 125I-labelled CEA, and anti-CEA serum were used. Plasma samples were taken from young healthy subjects (24), cancer-free hospital inpatients (44) and cancer-proven untreated patients (94). Within-batch and between-batch variation were both greater for the extracted-plasma method. Cancer discriminatory ability was assessed by probabilistic means. With cancer-free inpatients as the reference group, no difference between the assay methods was revealed. With young healthy subjects as the reference group the whole-plasma assay was superior.", "contents": "Comparison of whole plasma and perchloric acid-extracted plasma assays for carcinoembryonic antigen. A direct, paired, comparison was made of two plasma radioimmunoassays for carcinoembryonic antigen (CEA), between a perchloric acid-extracted, ammonium sulphate precipitation method; and a whole-plasma, double-antibody method. For both assays the same preparations of standard CEA, 125I-labelled CEA, and anti-CEA serum were used. Plasma samples were taken from young healthy subjects (24), cancer-free hospital inpatients (44) and cancer-proven untreated patients (94). Within-batch and between-batch variation were both greater for the extracted-plasma method. Cancer discriminatory ability was assessed by probabilistic means. With cancer-free inpatients as the reference group, no difference between the assay methods was revealed. With young healthy subjects as the reference group the whole-plasma assay was superior."}
{"id": "PMID:188570", "title": "Prenatal diagnosis of galactosemia.", "content": "Prenatal diagnosis of disorders of galactose metabolism was done in one instance in a family with a known galactokinase deficiency and in six cases in five families at risk for galactosemia. The galactokinase activity in cultured amniotic cells was found to be normal, and the diagnosis was confirmed postnatally. In the six pregnancies at risk for galactosemia, four were considered to be unaffected and two to be affected. Of the latter, one was carried to term, and the erythrocyte transferase activity of the baby was shown to be absent. The other pregnancy was terminated, and examination of fetal tissues by biochemical studies confirmed the diagnosis. This experience substantiates the concept that prenatal diagnosis of disorders of galactose metabolism is feasible.", "contents": "Prenatal diagnosis of galactosemia. Prenatal diagnosis of disorders of galactose metabolism was done in one instance in a family with a known galactokinase deficiency and in six cases in five families at risk for galactosemia. The galactokinase activity in cultured amniotic cells was found to be normal, and the diagnosis was confirmed postnatally. In the six pregnancies at risk for galactosemia, four were considered to be unaffected and two to be affected. Of the latter, one was carried to term, and the erythrocyte transferase activity of the baby was shown to be absent. The other pregnancy was terminated, and examination of fetal tissues by biochemical studies confirmed the diagnosis. This experience substantiates the concept that prenatal diagnosis of disorders of galactose metabolism is feasible."}
{"id": "PMID:188571", "title": "LHRH-pituitary plasma membrane binding: the presence of specific binding sites in other tissues.", "content": "Two specific binding sites for LHRH are present on plasma membranes prepared from rat and bovine anterior pituitary glands. One site is of high affinity (K = 2X108 1/MOL) and the second is of lower affinity (8-5X105 1/mol) and much greater capacity. Studies on membrane fractions prepared from other tissues showed the presence of a single specific site for LHRH. The kinetics and specificity of this site were similar to those of the lower affinity pituitary receptor. These results indicate that only pituitary membranes possess the higher affinity binding site and suggest that the low affinity site is not of physiological importance in the regulation of gonadotrophin secretion. After dissociation from membranes of non-pituitary tissues 125I-LHRH rebound to pituitary membrane preparations. Thus receptor binding per se does not result in degradation of LHRH and the function of these peripheral receptors remains obscure.", "contents": "LHRH-pituitary plasma membrane binding: the presence of specific binding sites in other tissues. Two specific binding sites for LHRH are present on plasma membranes prepared from rat and bovine anterior pituitary glands. One site is of high affinity (K = 2X108 1/MOL) and the second is of lower affinity (8-5X105 1/mol) and much greater capacity. Studies on membrane fractions prepared from other tissues showed the presence of a single specific site for LHRH. The kinetics and specificity of this site were similar to those of the lower affinity pituitary receptor. These results indicate that only pituitary membranes possess the higher affinity binding site and suggest that the low affinity site is not of physiological importance in the regulation of gonadotrophin secretion. After dissociation from membranes of non-pituitary tissues 125I-LHRH rebound to pituitary membrane preparations. Thus receptor binding per se does not result in degradation of LHRH and the function of these peripheral receptors remains obscure."}
{"id": "PMID:188577", "title": "Cell-mediated immunity (CMI) to human wart virus and wart-associated tissue antigens.", "content": "Lymphocyte transformation (LT) and leucocyte migration inhibition in agarose were used to demonstrate cell-mediated immune response to purified human wart virus and wart tissue extract in various subjects with warts and those without past history of warts. Most individuals bearing warts for less than 1 year duration showed positive cell-mediated responses to both the virus and tissue extract whereas very few of those who had warts for longer duration responded to either antigenic preparation. The difference was statistically significant. Subjects who had warts in the past also showed positive responses but these tended to decrease in degree with time. Surprisingly a group of subjects who never had warts before also responded to stimulation with the virus, but not to the extract. The positive response to stimulation with wart tissue extract reflects the presence of wart associated antigens other than the virus. Cell-mediated immunity against the wart virus and wart-associated antigens is probably important in preventing the persistence or even establishment of disease but this protective immunity is short-lived. The lack of quantitative correlation between LT and leucocyte migration inhibition demonstrable in this study suggests that these two are separate events in in vitro lymphocyte stimulation with antigens.", "contents": "Cell-mediated immunity (CMI) to human wart virus and wart-associated tissue antigens. Lymphocyte transformation (LT) and leucocyte migration inhibition in agarose were used to demonstrate cell-mediated immune response to purified human wart virus and wart tissue extract in various subjects with warts and those without past history of warts. Most individuals bearing warts for less than 1 year duration showed positive cell-mediated responses to both the virus and tissue extract whereas very few of those who had warts for longer duration responded to either antigenic preparation. The difference was statistically significant. Subjects who had warts in the past also showed positive responses but these tended to decrease in degree with time. Surprisingly a group of subjects who never had warts before also responded to stimulation with the virus, but not to the extract. The positive response to stimulation with wart tissue extract reflects the presence of wart associated antigens other than the virus. Cell-mediated immunity against the wart virus and wart-associated antigens is probably important in preventing the persistence or even establishment of disease but this protective immunity is short-lived. The lack of quantitative correlation between LT and leucocyte migration inhibition demonstrable in this study suggests that these two are separate events in in vitro lymphocyte stimulation with antigens."}
{"id": "PMID:188578", "title": "Neutrophilic granulocytes in acute bacterial infection. Sequential studies on lysozyme, myeloperoxidase and lactoferrin.", "content": "The changes in intraneutrophilic and plasma concentrations of the three antibacterial proteins lysozyme, lactoferrin, and myeloperoxidase were studied sequentially during acute bacterial infection in nine patients. Intraneutrophilic concentrations of the three proteins were decreased by more than 50% during the 1st week of infection, followed by a slow increase over the following 2 weeks. Nadir values coincided with maximal toxic granulation of the neutrophils. The data suggest that neutrophilic granulocytes are deficient during early bacterial infection, possibly because of deficient synthesis of antibacterial proteins in the bone marrow, and that neutrophil toxic granulation is the visual counterpart of this defect. The plasma concentrations of the three proteins showed considerable differences: whereas plasma lysozyme did not show any sequential changes, plasma myeloperoxidase was high at the start of infection and quickly decreased towards normal values, and plasma lactoferrin, high in the first samples, showed a secondary peak 1 week after onset of disease, before normalization was seen. These differences may result from differences in the signals are specific for the individual antibacterial protein and not for the different types of neutrophil granules.", "contents": "Neutrophilic granulocytes in acute bacterial infection. Sequential studies on lysozyme, myeloperoxidase and lactoferrin. The changes in intraneutrophilic and plasma concentrations of the three antibacterial proteins lysozyme, lactoferrin, and myeloperoxidase were studied sequentially during acute bacterial infection in nine patients. Intraneutrophilic concentrations of the three proteins were decreased by more than 50% during the 1st week of infection, followed by a slow increase over the following 2 weeks. Nadir values coincided with maximal toxic granulation of the neutrophils. The data suggest that neutrophilic granulocytes are deficient during early bacterial infection, possibly because of deficient synthesis of antibacterial proteins in the bone marrow, and that neutrophil toxic granulation is the visual counterpart of this defect. The plasma concentrations of the three proteins showed considerable differences: whereas plasma lysozyme did not show any sequential changes, plasma myeloperoxidase was high at the start of infection and quickly decreased towards normal values, and plasma lactoferrin, high in the first samples, showed a secondary peak 1 week after onset of disease, before normalization was seen. These differences may result from differences in the signals are specific for the individual antibacterial protein and not for the different types of neutrophil granules."}
{"id": "PMID:188579", "title": "Alteration of lymphocyte subpopulations with cytomegalovirus infection in infancy.", "content": "The distribution of immunoglobulin bearing (Ig+), T, and null lymphocyte subpopulations and the lymphocyte response to phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) were determined in three infants with cytomegalovirus (CMV) infection. These infants had significantly decreased percentages of T cells (13%, 29% and 40%) compared to age-matched controls (61 +/- 2%). Compensatory increases in the percentages of Ig+ and null cells occurred. Decreased lymphocyte reactivity to PHA and PWM occurred in two patients. Purified T cells from these patients had normal reactivity indicating a disproportion of T cells in the peripheral blood. These abnormalities may result from CMV infection of lymphocytes and could be responsible for prolonged CMV viruria.", "contents": "Alteration of lymphocyte subpopulations with cytomegalovirus infection in infancy. The distribution of immunoglobulin bearing (Ig+), T, and null lymphocyte subpopulations and the lymphocyte response to phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) were determined in three infants with cytomegalovirus (CMV) infection. These infants had significantly decreased percentages of T cells (13%, 29% and 40%) compared to age-matched controls (61 +/- 2%). Compensatory increases in the percentages of Ig+ and null cells occurred. Decreased lymphocyte reactivity to PHA and PWM occurred in two patients. Purified T cells from these patients had normal reactivity indicating a disproportion of T cells in the peripheral blood. These abnormalities may result from CMV infection of lymphocytes and could be responsible for prolonged CMV viruria."}
{"id": "PMID:188582", "title": "Abnormal 99mTechnetium-tin-pyrophosphate bone scans in chronic renal failure.", "content": "A high incidence of abnormal 99mTechnetium-tin-pyrophosphate (99mTcPPi) is reported in a population of chronic renal failure patients. Using the 5 hour bone to soft tissue ratio as a quantitative index of increased uptake, 78% of 45 long-term dialysis patients and a similar proportion of non-dialyzed chronic renal failure patients were found to have increased uptakes. In animal studies using a uremic model, similar increased uptakes of 99mTcPPi was found with evidence of increased vascularity as reflected by red cell or plasma volumes in the bone or by the uptake of concomitantly administered 45Ca. The evidence suggests that the abnormal bone scans reflect abnormalities in collagen metabolism that occurs in the uremic state and that 99mTcPPi scans are useful in the diagnosis and management of renal osteodystrophy.", "contents": "Abnormal 99mTechnetium-tin-pyrophosphate bone scans in chronic renal failure. A high incidence of abnormal 99mTechnetium-tin-pyrophosphate (99mTcPPi) is reported in a population of chronic renal failure patients. Using the 5 hour bone to soft tissue ratio as a quantitative index of increased uptake, 78% of 45 long-term dialysis patients and a similar proportion of non-dialyzed chronic renal failure patients were found to have increased uptakes. In animal studies using a uremic model, similar increased uptakes of 99mTcPPi was found with evidence of increased vascularity as reflected by red cell or plasma volumes in the bone or by the uptake of concomitantly administered 45Ca. The evidence suggests that the abnormal bone scans reflect abnormalities in collagen metabolism that occurs in the uremic state and that 99mTcPPi scans are useful in the diagnosis and management of renal osteodystrophy."}
{"id": "PMID:188580", "title": "Tetanic fade during partial transmission failure produced by non-depolarizing neuromuscular blocking drugs in the cat.", "content": "1. A comparison has been made of the effects of three acetylcholine antagonists--hexamethonium, tubocurarine and pancuronium--on maximal tetani of limb muscles of cats under chloralose anaesthesia. In most experiments, the indirectly stimulated soleus muscle was studied, but observations were also made on the tibialis anterior and flexor digitorum longus muscles. 2. When neuromuscular block was produced by intra-arterial injections of the acetylcholine antagonists, tetanic tension, though depressed in amplitude did not wane and there was little or no post-tetanic relief of the block as judged by the amplitude of subsequent twitches. On the other hand, during similar degrees of block produced by intravenous injections, tetanic tension rapidly waned, and, after the tetanus, transmission was temporarily facilitated, as evidenced by an increase in the amplitude of post-tetanic twitches. 3. Intravenously injected hexamethonium caused complete waning of tetanic tension in doses too small to depress twitch amplitude and which caused only a small depression of peak tetanic tension. In contrast, pancuronium caused only partial tetanic fade even in doses that produced pronounced depressions of twitch and tetanic tensions. The effects of tubocurarine fell between these extremes. 4. The results suggest that depression of peak tension and tetanic fade are independent effects of acetylcholine antagonists. It is postulated that the former is a consequence of block of post-junctional cholinoceptors, whereas the latter arises from an action of pre-junctional cholinoceptors. 5. The results obtained, together with those of other workers, led to the suggestion that transmitter acetylcholine, in addition to evoking the endplate potential, acts on the nonmyelinated nerve terminals in a positive feed-back mechanism that mobilizes transmitter to keep pace with release during high frequencies of stimulation.", "contents": "Tetanic fade during partial transmission failure produced by non-depolarizing neuromuscular blocking drugs in the cat. 1. A comparison has been made of the effects of three acetylcholine antagonists--hexamethonium, tubocurarine and pancuronium--on maximal tetani of limb muscles of cats under chloralose anaesthesia. In most experiments, the indirectly stimulated soleus muscle was studied, but observations were also made on the tibialis anterior and flexor digitorum longus muscles. 2. When neuromuscular block was produced by intra-arterial injections of the acetylcholine antagonists, tetanic tension, though depressed in amplitude did not wane and there was little or no post-tetanic relief of the block as judged by the amplitude of subsequent twitches. On the other hand, during similar degrees of block produced by intravenous injections, tetanic tension rapidly waned, and, after the tetanus, transmission was temporarily facilitated, as evidenced by an increase in the amplitude of post-tetanic twitches. 3. Intravenously injected hexamethonium caused complete waning of tetanic tension in doses too small to depress twitch amplitude and which caused only a small depression of peak tetanic tension. In contrast, pancuronium caused only partial tetanic fade even in doses that produced pronounced depressions of twitch and tetanic tensions. The effects of tubocurarine fell between these extremes. 4. The results suggest that depression of peak tension and tetanic fade are independent effects of acetylcholine antagonists. It is postulated that the former is a consequence of block of post-junctional cholinoceptors, whereas the latter arises from an action of pre-junctional cholinoceptors. 5. The results obtained, together with those of other workers, led to the suggestion that transmitter acetylcholine, in addition to evoking the endplate potential, acts on the nonmyelinated nerve terminals in a positive feed-back mechanism that mobilizes transmitter to keep pace with release during high frequencies of stimulation."}
{"id": "PMID:188581", "title": "Effects of clonidine on vascular responses in kidney and hindlimbs of cats.", "content": "1. Cardiovascular reflexes to intravenous adrenaline and histamine and to carotid occlusion were studied in the renal vasculature, and direct effects of noradrenaline and clinidoine were compared in renal and hindlimb vascular beds in anaesthetized cats. 2. Unlike its reported effects on cardiovascular reflexes in the hindlimbs, clonidine depressed all three reflexes in the kidneys. 3. Noradrenaline caused vasoconstriction when given directly into both renal and hindlimb circulartions, but clonidine produced vasoconstriction only in the hindlimb vascular bed. 4. These results suggest that alpha-adrenoceptors in the reanl vasculature may be different from those in the hindlimbs, and that the cardiovascular reflexes in these two areas are under different control.", "contents": "Effects of clonidine on vascular responses in kidney and hindlimbs of cats. 1. Cardiovascular reflexes to intravenous adrenaline and histamine and to carotid occlusion were studied in the renal vasculature, and direct effects of noradrenaline and clinidoine were compared in renal and hindlimb vascular beds in anaesthetized cats. 2. Unlike its reported effects on cardiovascular reflexes in the hindlimbs, clonidine depressed all three reflexes in the kidneys. 3. Noradrenaline caused vasoconstriction when given directly into both renal and hindlimb circulartions, but clonidine produced vasoconstriction only in the hindlimb vascular bed. 4. These results suggest that alpha-adrenoceptors in the reanl vasculature may be different from those in the hindlimbs, and that the cardiovascular reflexes in these two areas are under different control."}
{"id": "PMID:188591", "title": "Altered angiotensin I conversion in pulmonary disease.", "content": "1. A specific method is described for the measurement of angiotensin I converting enzyme activity in plasma with 125 I-labelled angiotensin I used as substrate. 2. Converting enzyme activity in plasma from fifteen normal subjects, eleven patients with sarcoidosis, twelve patients with chronic obstructive pulmonary disease and three patients with shock lung was assayed by this technique. 3. Patients with sarcoidosis had increased plasma converting enzyme activity whether or not they were receiving steroid therapy. 4. Patients with chronic obstructive pulmonary disease and shock lung had decreased plasma converting enzyme activity, but extent of conversion did not correlate with the severity of the lung disease. 5. Converting enzyme activity in normal plasma could be completely inhibited by addition of exogenous angiotensin I in 0.5-2.5x107 times physiological concentration. Twice as much exogenous angiotensin I was needed to inhibit conversion completely in plasma from patients with sarcoidosis; one tenth as much in chronic obstructive pulmonary disease. These results indicate that plasma has a high capacity for angiotensin I conversion even in patients with pulmonary parenchymal disease. 6. Results suggest that plasma converting enzyme activity may be a reflection of pulmonary conversion and can be altered by pulmonary disease. 7. Measurement of plasma converting enzyme activity may be useful in studies designed to characterize the regulatory role of converting enzyme in the renin-angiotensin system and in cardiovascular homeostasis.", "contents": "Altered angiotensin I conversion in pulmonary disease. 1. A specific method is described for the measurement of angiotensin I converting enzyme activity in plasma with 125 I-labelled angiotensin I used as substrate. 2. Converting enzyme activity in plasma from fifteen normal subjects, eleven patients with sarcoidosis, twelve patients with chronic obstructive pulmonary disease and three patients with shock lung was assayed by this technique. 3. Patients with sarcoidosis had increased plasma converting enzyme activity whether or not they were receiving steroid therapy. 4. Patients with chronic obstructive pulmonary disease and shock lung had decreased plasma converting enzyme activity, but extent of conversion did not correlate with the severity of the lung disease. 5. Converting enzyme activity in normal plasma could be completely inhibited by addition of exogenous angiotensin I in 0.5-2.5x107 times physiological concentration. Twice as much exogenous angiotensin I was needed to inhibit conversion completely in plasma from patients with sarcoidosis; one tenth as much in chronic obstructive pulmonary disease. These results indicate that plasma has a high capacity for angiotensin I conversion even in patients with pulmonary parenchymal disease. 6. Results suggest that plasma converting enzyme activity may be a reflection of pulmonary conversion and can be altered by pulmonary disease. 7. Measurement of plasma converting enzyme activity may be useful in studies designed to characterize the regulatory role of converting enzyme in the renin-angiotensin system and in cardiovascular homeostasis."}
{"id": "PMID:188594", "title": "Isolation of bluetongue vaccine virus from infected sheep by direct inoculation onto tissue culture.", "content": "A technique is described by which the vaccine strain of bluetongue virus (BTVV) may be isolated from infected fetal, neonatal, and adult sheep tissues utilizing tissue culture. The data from these studies provides evidence that 1) BTVV can be readily isolated from infected fetal and newborn tissues by tissue culture, 2) mild treatment of tissues and utilization of lysed cells as inoculum an effective means of recovering vaccine virus, 3) BTVV can be isolated with equal efficacy from mononuclear fractions and from erythrocyte granulocyte fractions of viremic blood, and 5) the brain of fetal lambs and the spleen and liver of neonatal lambs appear to be the tissues from which vaccine can be consistently isolated.", "contents": "Isolation of bluetongue vaccine virus from infected sheep by direct inoculation onto tissue culture. A technique is described by which the vaccine strain of bluetongue virus (BTVV) may be isolated from infected fetal, neonatal, and adult sheep tissues utilizing tissue culture. The data from these studies provides evidence that 1) BTVV can be readily isolated from infected fetal and newborn tissues by tissue culture, 2) mild treatment of tissues and utilization of lysed cells as inoculum an effective means of recovering vaccine virus, 3) BTVV can be isolated with equal efficacy from mononuclear fractions and from erythrocyte granulocyte fractions of viremic blood, and 5) the brain of fetal lambs and the spleen and liver of neonatal lambs appear to be the tissues from which vaccine can be consistently isolated."}
{"id": "PMID:188595", "title": "A paravaccinia virus isolated from cattle.", "content": "Isolation of viruses from calves with acute respiratory tract disease were attempted on bovine embryonic lung cell cultures. An isolate obtained from one calf with oral lesions and respiratory disease, designated 44-M-E482, was characterized as a paravaccinia virus on the basis of biological and physical properties. The calf from which the paravaccinia virus 44-M-E482 was isolated did not possess serum neutralizing antibody in its convalescent sera; neither did experimentally inoculated calves possess serum neutralizing antibody to the isolate. However, a low titer of serum neutralizing antibody was produced in one calf after several intravenous injections of the virus. Inoculation of calves with 44-M-E482 into the oral mucosa, skin, nasal cavity and pharynx did not cause any noticeable illness or lesions. The relation of 44-M-E482 to the viruses which cause bovine papular stomatitis and pseudocowpox is discussed.", "contents": "A paravaccinia virus isolated from cattle. Isolation of viruses from calves with acute respiratory tract disease were attempted on bovine embryonic lung cell cultures. An isolate obtained from one calf with oral lesions and respiratory disease, designated 44-M-E482, was characterized as a paravaccinia virus on the basis of biological and physical properties. The calf from which the paravaccinia virus 44-M-E482 was isolated did not possess serum neutralizing antibody in its convalescent sera; neither did experimentally inoculated calves possess serum neutralizing antibody to the isolate. However, a low titer of serum neutralizing antibody was produced in one calf after several intravenous injections of the virus. Inoculation of calves with 44-M-E482 into the oral mucosa, skin, nasal cavity and pharynx did not cause any noticeable illness or lesions. The relation of 44-M-E482 to the viruses which cause bovine papular stomatitis and pseudocowpox is discussed."}
{"id": "PMID:188600", "title": "Cytomegaloviral infection presenting as a solitary pulmonary nodule.", "content": "Cytomegaloviral infection presenting in an immunologically compromised host as a solitary pulmonary nodule has not previously been reported. A patient with a renal transplant and with no pulmonary symptoms was noted to have a single nodule on a chest roentgenogram. At autopsy, this proved to be secondary to cytomegaloviral infection. Differential diagnostic considerations in the immunosuppressed patient are discussed.", "contents": "Cytomegaloviral infection presenting as a solitary pulmonary nodule. Cytomegaloviral infection presenting in an immunologically compromised host as a solitary pulmonary nodule has not previously been reported. A patient with a renal transplant and with no pulmonary symptoms was noted to have a single nodule on a chest roentgenogram. At autopsy, this proved to be secondary to cytomegaloviral infection. Differential diagnostic considerations in the immunosuppressed patient are discussed."}
{"id": "PMID:188604", "title": "Antirival activity of N-phenyl-N'-arylthiourea derivatives against some Rhinoviruses.", "content": "The effect of 12 derivatives of N-phenyl-N'-aryl- or alkylthiourea, inhibitors of human enteroviruses and foot-and-mouth disease virus, on reproduction of some rhinoviruses (H-17, B-632) in HeLa Bristol cells was studied. As screening methods both the multicylce growth test in roller tube cultures and two variants of plaque inhibition tests were employed. The compounds selected were tested in one-step growth cycle set-up. We established that N-phenyl-N'-4-hydroxyphenylthiourea (V-24) and N-phenyl-N'-2-carboxyphenylthiourea (V-17) have a distinct inhibitory effect on the growth of rhinovirus H-17, and N-phenyl-N'-2-hydroxy-5-nitrophenylthiourea (V-25) inhibited strongly the multiplication of rhinovirus B-632.", "contents": "Antirival activity of N-phenyl-N'-arylthiourea derivatives against some Rhinoviruses. The effect of 12 derivatives of N-phenyl-N'-aryl- or alkylthiourea, inhibitors of human enteroviruses and foot-and-mouth disease virus, on reproduction of some rhinoviruses (H-17, B-632) in HeLa Bristol cells was studied. As screening methods both the multicylce growth test in roller tube cultures and two variants of plaque inhibition tests were employed. The compounds selected were tested in one-step growth cycle set-up. We established that N-phenyl-N'-4-hydroxyphenylthiourea (V-24) and N-phenyl-N'-2-carboxyphenylthiourea (V-17) have a distinct inhibitory effect on the growth of rhinovirus H-17, and N-phenyl-N'-2-hydroxy-5-nitrophenylthiourea (V-25) inhibited strongly the multiplication of rhinovirus B-632."}
{"id": "PMID:188606", "title": "Focal dermal hypoplasia (Goltz's syndrome) manifesting as condyloma acuminatum: report of a case and review of the literature.", "content": "A new case of Goltz's syndrome, focal dermal hypoplasia, is documented. The literature is reviewed. The composite individuality warrants considering Golt'z syndrome a separate syndrome in the ectodermal dysplasias. Caution against diagnosing \"condyloma-like\" lesions occurring in ectodermally dysplastic patients as condyloma acuminatum is urged. Neoplastic transformation and the tendency to recurrence after surgical exicision of the cutaneous angiofibromas pose a difficult problem in surgical management.", "contents": "Focal dermal hypoplasia (Goltz's syndrome) manifesting as condyloma acuminatum: report of a case and review of the literature. A new case of Goltz's syndrome, focal dermal hypoplasia, is documented. The literature is reviewed. The composite individuality warrants considering Golt'z syndrome a separate syndrome in the ectodermal dysplasias. Caution against diagnosing \"condyloma-like\" lesions occurring in ectodermally dysplastic patients as condyloma acuminatum is urged. Neoplastic transformation and the tendency to recurrence after surgical exicision of the cutaneous angiofibromas pose a difficult problem in surgical management."}
{"id": "PMID:188621", "title": "[Post-perfusion syndrome in childhood (author's transl)].", "content": "Following cardiac surgery with extracorporeal circulation three children became ill with a postperfusion syndrome. Besides typical clinical and haematological findings (fever, hepatosplenomegaly, lymphomonocytosis with \"atypical\" lymphocytes) demonstration of characteristic antibody sequential titres (IgG and IgM antibodies against cytomegalovirus) was possible. The importance of this syndrome rests in the problems of differential diagnosis which occur at the beginning of clinical symptoms (differentiation from endocarditis, septicaemia, hepatitis).", "contents": "[Post-perfusion syndrome in childhood (author's transl)]. Following cardiac surgery with extracorporeal circulation three children became ill with a postperfusion syndrome. Besides typical clinical and haematological findings (fever, hepatosplenomegaly, lymphomonocytosis with \"atypical\" lymphocytes) demonstration of characteristic antibody sequential titres (IgG and IgM antibodies against cytomegalovirus) was possible. The importance of this syndrome rests in the problems of differential diagnosis which occur at the beginning of clinical symptoms (differentiation from endocarditis, septicaemia, hepatitis)."}
{"id": "PMID:188622", "title": "[Comparative studies on the removal of dental plaque by means of various dentifrices].", "content": "In order to demonstrate the cleaning effect of toothpastes which differed with regard to their percentage of polishing and wetting agents, we tested and compared different pastes (\"W,X,Y,Z\") to each other and with a placebo paste (\"V\") in 53 subjects. In a double blind trial, the Silness and L\u00f6e, Quigley and Hein plaque indices were determined, after establishing the initial values, and after two (interim measurement) and four weeks (final measurement) of application. Statistical evaluation showed that the toothpaste \"w\" with the components calcium phosphate, sodium laurylsulfate and sodium sulforicinoleate (in the given concentrations) cleans accessible dental surfaces from plaque and discolorations most intensively. All pastes were statistically significantly different from the control paste.", "contents": "[Comparative studies on the removal of dental plaque by means of various dentifrices]. In order to demonstrate the cleaning effect of toothpastes which differed with regard to their percentage of polishing and wetting agents, we tested and compared different pastes (\"W,X,Y,Z\") to each other and with a placebo paste (\"V\") in 53 subjects. In a double blind trial, the Silness and L\u00f6e, Quigley and Hein plaque indices were determined, after establishing the initial values, and after two (interim measurement) and four weeks (final measurement) of application. Statistical evaluation showed that the toothpaste \"w\" with the components calcium phosphate, sodium laurylsulfate and sodium sulforicinoleate (in the given concentrations) cleans accessible dental surfaces from plaque and discolorations most intensively. All pastes were statistically significantly different from the control paste."}
{"id": "PMID:188623", "title": "[After care of periodontally treated patients].", "content": "Follow-up examinations is mandatory with periodontal therapy in order to check the risk of recurrence. It comprises periodic check-ups, in which, at first, gingival inflammations and plaque causing such inflammation are evaluated together with the patient. Still in the same session, this is followed by conservative therapy. Apart from exact supra- and subgingival scaling, it is important to control and reinstruct the patient in personal oral hygiene. Interdental hygiene and the adjuncts selected according to the width of the inter-dental space play an important role in preventing inflammation. The time required for follow-up examinations in patients with periodontal disease calls for auxiliary personnel, especially the fully qualified dental hygienist.", "contents": "[After care of periodontally treated patients]. Follow-up examinations is mandatory with periodontal therapy in order to check the risk of recurrence. It comprises periodic check-ups, in which, at first, gingival inflammations and plaque causing such inflammation are evaluated together with the patient. Still in the same session, this is followed by conservative therapy. Apart from exact supra- and subgingival scaling, it is important to control and reinstruct the patient in personal oral hygiene. Interdental hygiene and the adjuncts selected according to the width of the inter-dental space play an important role in preventing inflammation. The time required for follow-up examinations in patients with periodontal disease calls for auxiliary personnel, especially the fully qualified dental hygienist."}
{"id": "PMID:188625", "title": "Effects of methylxanthines on gonadotropin-induced steroidogenesis and protein synthesis in isolated testis interstitial cells.", "content": "The effects of 1-methyl 3-isobutyl xanthine (MIX) and theophylline on basal and gonadotropin-stimulated production of cyclic AMP and testosterone were evaluated in enzyme-dispersed testicular interstitial cells. The actions of these compounds upon precursor incorporation into RNA and protein were also examined in the same cell preparation. The considerable higher potency of MIX as a phosphodiesterase inhibitor was accompanied by a steeper dose-response curve for cyclic AMP recovery in incubation media of hormone-treated cells. Both inhibitors caused increases in basal and hormone-stimulated cyclic AMP levels. Although low concentrations of theophylline and MIX had no effect on the maximum levels of hCG-stimulated testosterone production, 10 mM theophylline and 1 mM MIX significantly inhibited steroidogenesis. Conversely, basal testosterone levels were increased by MIX and theophylline. The higher concentrations of MIX and theophylline also significantly inhibited precursor incorporation into RNA and protein. These actions of phosphodiesterase inhibitors upon RNA and protein synthesis could contribute to their inhibitory effects at high concentrations upon gonadotropin-induced steroidogenesis.", "contents": "Effects of methylxanthines on gonadotropin-induced steroidogenesis and protein synthesis in isolated testis interstitial cells. The effects of 1-methyl 3-isobutyl xanthine (MIX) and theophylline on basal and gonadotropin-stimulated production of cyclic AMP and testosterone were evaluated in enzyme-dispersed testicular interstitial cells. The actions of these compounds upon precursor incorporation into RNA and protein were also examined in the same cell preparation. The considerable higher potency of MIX as a phosphodiesterase inhibitor was accompanied by a steeper dose-response curve for cyclic AMP recovery in incubation media of hormone-treated cells. Both inhibitors caused increases in basal and hormone-stimulated cyclic AMP levels. Although low concentrations of theophylline and MIX had no effect on the maximum levels of hCG-stimulated testosterone production, 10 mM theophylline and 1 mM MIX significantly inhibited steroidogenesis. Conversely, basal testosterone levels were increased by MIX and theophylline. The higher concentrations of MIX and theophylline also significantly inhibited precursor incorporation into RNA and protein. These actions of phosphodiesterase inhibitors upon RNA and protein synthesis could contribute to their inhibitory effects at high concentrations upon gonadotropin-induced steroidogenesis."}
{"id": "PMID:188626", "title": "Parathyroid hormone-mediated incorporation of 32P-orthophosphate into phosphatidic acid and phosphatidylinositol in renal cortical slices.", "content": "Parathyroid hormone increased the incorporation of Na2H32PO4 into phosphatidic acid and phosphatidylinositol in cat renal cortical slices. Incorporation was not observed into any other phospholipid. The effects were seen as early as one minute for phosphatidic acid and ten minutes for phosphatidylinositol. 8-Bromoadnosine 3',5'-monophosphate did not mimic the effects of parathyroid hormone. Concentrations of parathyroid hormone, 1 x 10(-8)M to 1 x 10(-7)M, which increased the incorporation of 32p into phosphatidic acid and phosphatidylinositol maximally, did not alter tissue cyclic AMP levels suggesting that the incorporation of 32p was independent of cyclic AMP.", "contents": "Parathyroid hormone-mediated incorporation of 32P-orthophosphate into phosphatidic acid and phosphatidylinositol in renal cortical slices. Parathyroid hormone increased the incorporation of Na2H32PO4 into phosphatidic acid and phosphatidylinositol in cat renal cortical slices. Incorporation was not observed into any other phospholipid. The effects were seen as early as one minute for phosphatidic acid and ten minutes for phosphatidylinositol. 8-Bromoadnosine 3',5'-monophosphate did not mimic the effects of parathyroid hormone. Concentrations of parathyroid hormone, 1 x 10(-8)M to 1 x 10(-7)M, which increased the incorporation of 32p into phosphatidic acid and phosphatidylinositol maximally, did not alter tissue cyclic AMP levels suggesting that the incorporation of 32p was independent of cyclic AMP."}
{"id": "PMID:188627", "title": "Role of 5'-guanylylimidodiphosphate in the activation of adenylyl cyclase by parathyroid hormone.", "content": "We have studied the effects of guanylylimidodiphosphate (Gpp(NH)p), an analogue of GTP, on the stimulation of renal cortical adenylyl cyclase by bovine parathyroid hormone (bPTH, or bPTH-(1-84)). Incubation of canine renal membranes with bPTH-(3-34), a specific antagonist of parathyroid hormone, in either the presence or absence of Gpp(NH)p, prevented subsequently added bPTH-(1-84) from stimulating adenylyl cyclase. The addition of the antagonist to a cyclase system previously activated by both bPTH-(1-84) and Gpp(NH)p, however, produced no inhibition of enzyme activity. Removal of bPTH by washing the membranes virtually abolished activity, but washing after addition of bPTH plus Gpp(NH)p did not prevent continued accumulation of cAMP. The persistence of the activity of the enzyme brought about by the addition of Gpp(NH)p plus bPTH, despite washing or addition of specific inhibitor of bPTH action, indicates that the activity of the hormone-specific adenylyl cyclase in membrane suspensions is independent of cintinuous occupancy of the peptide-hormone receptor by bPTH in the presence of the guanyl-nucleotide analogue.", "contents": "Role of 5'-guanylylimidodiphosphate in the activation of adenylyl cyclase by parathyroid hormone. We have studied the effects of guanylylimidodiphosphate (Gpp(NH)p), an analogue of GTP, on the stimulation of renal cortical adenylyl cyclase by bovine parathyroid hormone (bPTH, or bPTH-(1-84)). Incubation of canine renal membranes with bPTH-(3-34), a specific antagonist of parathyroid hormone, in either the presence or absence of Gpp(NH)p, prevented subsequently added bPTH-(1-84) from stimulating adenylyl cyclase. The addition of the antagonist to a cyclase system previously activated by both bPTH-(1-84) and Gpp(NH)p, however, produced no inhibition of enzyme activity. Removal of bPTH by washing the membranes virtually abolished activity, but washing after addition of bPTH plus Gpp(NH)p did not prevent continued accumulation of cAMP. The persistence of the activity of the enzyme brought about by the addition of Gpp(NH)p plus bPTH, despite washing or addition of specific inhibitor of bPTH action, indicates that the activity of the hormone-specific adenylyl cyclase in membrane suspensions is independent of cintinuous occupancy of the peptide-hormone receptor by bPTH in the presence of the guanyl-nucleotide analogue."}
{"id": "PMID:188628", "title": "Aldosterone production by isolated glomerulosa cells: modulation of sensitivity to angiotensin II and ACTH by extracellular potassium concentration.", "content": "The influence of extracellular potassium concentration on adrenal sensitivity to angiotensin II and ACTH was studied in isolated canine adrenal glomerulosa cells. When potassium was absent from the incubation medium, the aldosterone response to angiotensin II or ACTH was completely abolished. At physiologic angiotensin II concentrations (2.5 x 10(-11) M), aldosterone formation increased 4-fold when potassium concentration was increased from 2.5 to 5.0 mM, and rose 6-fold as potassium was increased from 2.5 to 7.5 mM. In the absence of angiotensin II, the same changes in potassium concentration increased aldosterone production only to 2-fold and 3.5-fold, respectively. The effect of potassium concentration upon the aldosterone response to ACTH was similar but less marked. The concentration and binding affinity of angiotensin II receptor sites in glomerulosa cells were not changed by increasing potassium concentrations from 0 to 7.5 mM. These observations demonstrate that the aldosterone response to the glomerulosa cell to angiotensin II is potassium-dependent within the physiological range for each of these stimuli. Such an interaction suggests that the in vivo effect of potassium upon aldosterone secretion includes a significant modulating action upon adrenal sensitivity to angiotensin II, as well as a direct action of potassium upon the adrenal glomerulosa cell.", "contents": "Aldosterone production by isolated glomerulosa cells: modulation of sensitivity to angiotensin II and ACTH by extracellular potassium concentration. The influence of extracellular potassium concentration on adrenal sensitivity to angiotensin II and ACTH was studied in isolated canine adrenal glomerulosa cells. When potassium was absent from the incubation medium, the aldosterone response to angiotensin II or ACTH was completely abolished. At physiologic angiotensin II concentrations (2.5 x 10(-11) M), aldosterone formation increased 4-fold when potassium concentration was increased from 2.5 to 5.0 mM, and rose 6-fold as potassium was increased from 2.5 to 7.5 mM. In the absence of angiotensin II, the same changes in potassium concentration increased aldosterone production only to 2-fold and 3.5-fold, respectively. The effect of potassium concentration upon the aldosterone response to ACTH was similar but less marked. The concentration and binding affinity of angiotensin II receptor sites in glomerulosa cells were not changed by increasing potassium concentrations from 0 to 7.5 mM. These observations demonstrate that the aldosterone response to the glomerulosa cell to angiotensin II is potassium-dependent within the physiological range for each of these stimuli. Such an interaction suggests that the in vivo effect of potassium upon aldosterone secretion includes a significant modulating action upon adrenal sensitivity to angiotensin II, as well as a direct action of potassium upon the adrenal glomerulosa cell."}
{"id": "PMID:188629", "title": "On the role of the central noradrenergic and dopaminergic systems in the regulation of TSH secretion in the rat.", "content": "Systemic administration of drugs affecting central noradrenergic and dopaminergic systems was used to evaluate their role in the regulation of TSH secretion in the rat. Alpha-methyl-p-tyrosine (alpha-MT) caused a depletion of brain norepinephrine and dopamine and a gradual decrease of serum TSH levels. Specific inhibitors of dopamine-beta-hydroxylase, diethyldithiocarbamate (DDC) and FLA 63, depleted central norepinephrine only and led to a simultaneous striking decrease of serum TSH. Blockade of alpha adrenergic receptors with phenoxybenzamine, but not with phentolamine, also depressed serum TSH. Blockade of beta receptors with propranolol had no effect. In contrast, the centrally and peripherally acting alpha receptor agonist, clonidine, increased serum TSH, whereas the peripherally acting methoxamine caused a decrease, probably due to non specific stress effect. A dose-related rapid inhibition of TSH secretion was observed following stimulation of dopamine receptors with apomorphine. Injection of L-Dopa had a similar effect. Blockade of the dopamine receptors with pimozide did not alter serum TSH, while blockade with spiroperidol led to a slight increase. The cold-induced surgeof TSH was abolished by pretreatment with DDC or phenoxybenzamine, reduced by apomorphine, but unaffected by pimozide or propranolol. The pituitary responsiveness to exogenous TRH was unaffected by administration of DDC or apomorphine. On the basis of these results, it is assumed that the central noradrenergic system has a stimulatory effect on the release of TRH from the hypothalamus, reflected in our experiments by the changes of serum TSH levels. It probably provides the drive for the tonic release of TRH in resting conditions and stimuli for the enhanced secretion during cold exposure. The effect is probably mediated by a central alpha-adrenergic mechanism. Activation of the dopaminergic system is inhibitory, but the physiological role of this effect remains to be established.", "contents": "On the role of the central noradrenergic and dopaminergic systems in the regulation of TSH secretion in the rat. Systemic administration of drugs affecting central noradrenergic and dopaminergic systems was used to evaluate their role in the regulation of TSH secretion in the rat. Alpha-methyl-p-tyrosine (alpha-MT) caused a depletion of brain norepinephrine and dopamine and a gradual decrease of serum TSH levels. Specific inhibitors of dopamine-beta-hydroxylase, diethyldithiocarbamate (DDC) and FLA 63, depleted central norepinephrine only and led to a simultaneous striking decrease of serum TSH. Blockade of alpha adrenergic receptors with phenoxybenzamine, but not with phentolamine, also depressed serum TSH. Blockade of beta receptors with propranolol had no effect. In contrast, the centrally and peripherally acting alpha receptor agonist, clonidine, increased serum TSH, whereas the peripherally acting methoxamine caused a decrease, probably due to non specific stress effect. A dose-related rapid inhibition of TSH secretion was observed following stimulation of dopamine receptors with apomorphine. Injection of L-Dopa had a similar effect. Blockade of the dopamine receptors with pimozide did not alter serum TSH, while blockade with spiroperidol led to a slight increase. The cold-induced surgeof TSH was abolished by pretreatment with DDC or phenoxybenzamine, reduced by apomorphine, but unaffected by pimozide or propranolol. The pituitary responsiveness to exogenous TRH was unaffected by administration of DDC or apomorphine. On the basis of these results, it is assumed that the central noradrenergic system has a stimulatory effect on the release of TRH from the hypothalamus, reflected in our experiments by the changes of serum TSH levels. It probably provides the drive for the tonic release of TRH in resting conditions and stimuli for the enhanced secretion during cold exposure. The effect is probably mediated by a central alpha-adrenergic mechanism. Activation of the dopaminergic system is inhibitory, but the physiological role of this effect remains to be established."}
{"id": "PMID:188630", "title": "Regulation of casein synthesis by polyamines in mammary gland explants of mice.", "content": "Studies were carried out to determine whether the actions of prolactin on the metabolism of the mammary gland may involve polyamines. In mouse mammary gland explants that were preincubated for 2 days with insulin plus hydrocortisone, the rate of [3H]leucine incorporation into casein was enhanced in a prolactin-like manner during a further incubation with spermidine plus cyclic GMP or phospholipase A. Putrescine (0.5 mM) plus PGF2alpha, cyclic GMP or arachidonic acid also enhanced the rate of casein synthesis: but PGF2alpha plus 0.5 mM arginine, ornithine or spermine had no effect. Methyl GAG, an inhibitor of the enzyme S-adenosyl-L-methionine decarboxylase (which is required for the conversion of putrescine to spermidine), abolished the putrescine plus PGF2alpha stimulation of casein synthesis. Since this drug did not affect the action of spermidine plus PGF2alpha on casein synthesis, the specific action of spermidine on casein synthesis is suggested. Neither arginine, ornithine nor the polyamines, by themselves, affected the rate of [3H]uridine incorporation into RNA or the rate of [3H]leucine incorporation into casein. Spermidine levels were elevated within 4 h after adding prolactin to explants which were preincubated for 2 days with insulin plus hydrocortisone; this effect was apparent during incubation periods of up to 48 h with prolactin. Arginase and ornithine decarboxylase activities were also elevated in response to prolactin. Arginase activity was only elevated, however, during long incubation periods with prolactin, i.e., during incubation periods of longer than 2 days. In contrast, ornithine decarboxylase activity was elevated by prolactin within a 30 min incubation period; this effect was maximal after 2 h and persisted during exposure periods of up to 24 h.", "contents": "Regulation of casein synthesis by polyamines in mammary gland explants of mice. Studies were carried out to determine whether the actions of prolactin on the metabolism of the mammary gland may involve polyamines. In mouse mammary gland explants that were preincubated for 2 days with insulin plus hydrocortisone, the rate of [3H]leucine incorporation into casein was enhanced in a prolactin-like manner during a further incubation with spermidine plus cyclic GMP or phospholipase A. Putrescine (0.5 mM) plus PGF2alpha, cyclic GMP or arachidonic acid also enhanced the rate of casein synthesis: but PGF2alpha plus 0.5 mM arginine, ornithine or spermine had no effect. Methyl GAG, an inhibitor of the enzyme S-adenosyl-L-methionine decarboxylase (which is required for the conversion of putrescine to spermidine), abolished the putrescine plus PGF2alpha stimulation of casein synthesis. Since this drug did not affect the action of spermidine plus PGF2alpha on casein synthesis, the specific action of spermidine on casein synthesis is suggested. Neither arginine, ornithine nor the polyamines, by themselves, affected the rate of [3H]uridine incorporation into RNA or the rate of [3H]leucine incorporation into casein. Spermidine levels were elevated within 4 h after adding prolactin to explants which were preincubated for 2 days with insulin plus hydrocortisone; this effect was apparent during incubation periods of up to 48 h with prolactin. Arginase and ornithine decarboxylase activities were also elevated in response to prolactin. Arginase activity was only elevated, however, during long incubation periods with prolactin, i.e., during incubation periods of longer than 2 days. In contrast, ornithine decarboxylase activity was elevated by prolactin within a 30 min incubation period; this effect was maximal after 2 h and persisted during exposure periods of up to 24 h."}
{"id": "PMID:188631", "title": "Isolation of a somatomedin from plasma of rats bearing growth hormone secreting tumors.", "content": "We have purified a protein which has somatomedin-like properties from the serum of Wistar-Furth rats bearing a growth hormone producing pituitary tumor (MStT/W15). Activity was measured by a placental insulin and/or somatomedin C radioreceptor assay (SmC-RRA). The serum was initially filtered through Sephadex G-150 equilibrated with 0.1 M NH4HCO3 and 0.02% NaN3. On the G-150 column, radioreceptor insulin (RRI) and radioreceptor somatomedin C (RRSm-C) activities coincided and appeared predominantly in the 160,000 mol wt range with a minor proportion in the 50,000 mol wt range. The pooled active fractions were boiled for 30 min at pH 5.5. After removing denatured protein by centrifugation, the extract was passed through G-50 Sephadex equilibrated with 1% formic acid and 0.15 M NaCl. Sixty to 90% of the SmC-RRA activity in the effluent appeared in the 9000 mol wt range. This material has an isoelectric focusing range of 8.4--9.6, similar to that described for human somatomedin C. On SDS-urea polyacrylamide gel electrophoresis only one protein band was seen. The isolated peptide (rSm) stimulated sulfate uptake in hypophysectomized rat cartilage. The potency of two preparations was variously assayed from 14.0 to 54.7 units/mg. Rat somatomedin was iodinated and purified by absorption on and elution from placental membranes. Eight to 12% of rat [125I]Sm was specifically bound by human placental membranes. Rat [125I]Sm was displaced by hSmC and rSm and human NSILA-S, partially displaced by procine proinsulin and poorly displaced by rat insulin. In preliminary studies, rat [125I]Sm was displaced from receptors on human placental membranes by sera from pituitary tumor bearing rats greater than normal rat sera greater than hypophysectomized rat sera.", "contents": "Isolation of a somatomedin from plasma of rats bearing growth hormone secreting tumors. We have purified a protein which has somatomedin-like properties from the serum of Wistar-Furth rats bearing a growth hormone producing pituitary tumor (MStT/W15). Activity was measured by a placental insulin and/or somatomedin C radioreceptor assay (SmC-RRA). The serum was initially filtered through Sephadex G-150 equilibrated with 0.1 M NH4HCO3 and 0.02% NaN3. On the G-150 column, radioreceptor insulin (RRI) and radioreceptor somatomedin C (RRSm-C) activities coincided and appeared predominantly in the 160,000 mol wt range with a minor proportion in the 50,000 mol wt range. The pooled active fractions were boiled for 30 min at pH 5.5. After removing denatured protein by centrifugation, the extract was passed through G-50 Sephadex equilibrated with 1% formic acid and 0.15 M NaCl. Sixty to 90% of the SmC-RRA activity in the effluent appeared in the 9000 mol wt range. This material has an isoelectric focusing range of 8.4--9.6, similar to that described for human somatomedin C. On SDS-urea polyacrylamide gel electrophoresis only one protein band was seen. The isolated peptide (rSm) stimulated sulfate uptake in hypophysectomized rat cartilage. The potency of two preparations was variously assayed from 14.0 to 54.7 units/mg. Rat somatomedin was iodinated and purified by absorption on and elution from placental membranes. Eight to 12% of rat [125I]Sm was specifically bound by human placental membranes. Rat [125I]Sm was displaced by hSmC and rSm and human NSILA-S, partially displaced by procine proinsulin and poorly displaced by rat insulin. In preliminary studies, rat [125I]Sm was displaced from receptors on human placental membranes by sera from pituitary tumor bearing rats greater than normal rat sera greater than hypophysectomized rat sera."}
{"id": "PMID:188632", "title": "Effect of hormones on collagen metabolism and collagenase activity in the pubic symphysis ligament of the guinea pig.", "content": "The ligament which forms between the pubic bones of the pregnant guinea pig offers a unique system for the study of hormonal regulation of connective tissue metabolism. During the 5 days prior to parturition the length and hydroxyproline content of the pubic symphysis increase threefold. In nonpregnant animals, ligament growth can be induced in an estrogen-primed animal only following the administration of the hormone relaxin. A further increase in length can be achieved when progesterone is also injected. Removal and culture of post-partum ligaments, which undergo a 75% reduction in length and hydroxyproline content by the fifth post-partum day, allowed the demonstration of high collagenase levels released into the media. In contrast, when ligaments from pre-partum period were cultured, low levels of collagenase were detected in the media. The rapid post-partum ligament resorption could be partially inhibited if estrogen was injected immediately following parturition, whereas progesterone or relaxin significantly impaired ligament resorption. In a corresponding fashion, when the collagenase levels of these ligaments were measured progesterone treatment was shown to inhibit collagenase activity markedly while estrogen was less effective. Relaxin however, appeared to have no direct inhibitory effect.", "contents": "Effect of hormones on collagen metabolism and collagenase activity in the pubic symphysis ligament of the guinea pig. The ligament which forms between the pubic bones of the pregnant guinea pig offers a unique system for the study of hormonal regulation of connective tissue metabolism. During the 5 days prior to parturition the length and hydroxyproline content of the pubic symphysis increase threefold. In nonpregnant animals, ligament growth can be induced in an estrogen-primed animal only following the administration of the hormone relaxin. A further increase in length can be achieved when progesterone is also injected. Removal and culture of post-partum ligaments, which undergo a 75% reduction in length and hydroxyproline content by the fifth post-partum day, allowed the demonstration of high collagenase levels released into the media. In contrast, when ligaments from pre-partum period were cultured, low levels of collagenase were detected in the media. The rapid post-partum ligament resorption could be partially inhibited if estrogen was injected immediately following parturition, whereas progesterone or relaxin significantly impaired ligament resorption. In a corresponding fashion, when the collagenase levels of these ligaments were measured progesterone treatment was shown to inhibit collagenase activity markedly while estrogen was less effective. Relaxin however, appeared to have no direct inhibitory effect."}
{"id": "PMID:188633", "title": "Development of 1,25-dihydroxycholecalciferol receptor in the duodenal cytosol of chick embryo.", "content": "The development of 1,25-(OH)2D3 receptor in the duodenal cytosol of chick embryo was studied by the sucrose density gradient analysis. The binding profile for 1,25-(OH)2D3 in the cytosol of vitamin D-deficient chick duodenum on the sucrose density gradient revealed 3 binding components, and the sedimentation constant was estimated as 2.5, 3.5 and 5.5S respectively. The 3.5S binding component has high affinity and low capacity for 1,25-(OH)2D3 and is thought to be 1,25-(OH)2D3 receptor. During the development of chick embryo, the 3.5S binding component was not detected in 13-day embryonic duodenum, it appeared on 15th day of incubation and then gradually increased to the level of vitamin D-deficient chick on 19th day of incubation. The 5.5S binding component was specific for 25-OH-D3 and it was found even in 13-day embryo, but it did not show any significant change during development. On the other hand, the 2.5S component was not specific for either 1,25-(OH)2D3 or 25-OH-D3. However, it was main binding component in early stages of development and decreased during development. From these results, it is suggested that the receptor for 1,25-(OH)2D3 is available a few days before hatching and the inability to produce CaBP in the duodenum of chick embryo could not be ascribed to the absence of the receptor.", "contents": "Development of 1,25-dihydroxycholecalciferol receptor in the duodenal cytosol of chick embryo. The development of 1,25-(OH)2D3 receptor in the duodenal cytosol of chick embryo was studied by the sucrose density gradient analysis. The binding profile for 1,25-(OH)2D3 in the cytosol of vitamin D-deficient chick duodenum on the sucrose density gradient revealed 3 binding components, and the sedimentation constant was estimated as 2.5, 3.5 and 5.5S respectively. The 3.5S binding component has high affinity and low capacity for 1,25-(OH)2D3 and is thought to be 1,25-(OH)2D3 receptor. During the development of chick embryo, the 3.5S binding component was not detected in 13-day embryonic duodenum, it appeared on 15th day of incubation and then gradually increased to the level of vitamin D-deficient chick on 19th day of incubation. The 5.5S binding component was specific for 25-OH-D3 and it was found even in 13-day embryo, but it did not show any significant change during development. On the other hand, the 2.5S component was not specific for either 1,25-(OH)2D3 or 25-OH-D3. However, it was main binding component in early stages of development and decreased during development. From these results, it is suggested that the receptor for 1,25-(OH)2D3 is available a few days before hatching and the inability to produce CaBP in the duodenum of chick embryo could not be ascribed to the absence of the receptor."}
{"id": "PMID:188634", "title": "Effects of mannoheptulose and DL-glyceraldehyde on glucose induced insulin release and adenosine 3',5'-monophosphate levels in isoalted islets of rat pancreas.", "content": "The effects of mannoheptulose and DL-glyceraldehyde on glucose-induced insulin release and cycli AMP levels in islets isolated from rat pancreas were investigated. Mannoheptulose inhibition on glucose-induced insulin release was observed after only 5-min incubation period, indicating an inhibitory effect on the early phase of insulin release. This inhibition on insulin release was accompanied with the simultaneous depression of cyclic AMP levels in islets. By the addition of DL-glyceraldehyde to the medium in which glucose and mannoheptulose were present, the depressed cyclic AMP levels in islets were recovered to the control level completely but the restoration of insulin release in the early phase was not complete. In the absence of glucose, DL-glyceraldehyde did not demonstrate a significant increase of insulin release during 5 min incubation, though a marked stimulation was observed after 30-min incubation. Cyclic AMP levels in islets were not affected by DL-glyceraldehyde. When DL-glyceraldehyde was added to the medium with glucose, significant inhibition of glucos-induced insulin release in its early phase was observed without the reduction of cyclic AMP levels in islets. From these findings, the following possibilities are suggested and discussed. 1. Maintenance of the cyclic AMP levels in islets is a necessary but insufficient condition for glucose-induced insulin release particularly for its early phase. 2. Glucose-induced insulin release seems to depend on both the binding of glucose with glucoreceptor and the supply of some metabolites. Mannoheptulose inhibits both mechanisms. DL-glyceraldehyde may supply metabolites but competitively inhibit the binding of glucose to the glucoreceptor.", "contents": "Effects of mannoheptulose and DL-glyceraldehyde on glucose induced insulin release and adenosine 3',5'-monophosphate levels in isoalted islets of rat pancreas. The effects of mannoheptulose and DL-glyceraldehyde on glucose-induced insulin release and cycli AMP levels in islets isolated from rat pancreas were investigated. Mannoheptulose inhibition on glucose-induced insulin release was observed after only 5-min incubation period, indicating an inhibitory effect on the early phase of insulin release. This inhibition on insulin release was accompanied with the simultaneous depression of cyclic AMP levels in islets. By the addition of DL-glyceraldehyde to the medium in which glucose and mannoheptulose were present, the depressed cyclic AMP levels in islets were recovered to the control level completely but the restoration of insulin release in the early phase was not complete. In the absence of glucose, DL-glyceraldehyde did not demonstrate a significant increase of insulin release during 5 min incubation, though a marked stimulation was observed after 30-min incubation. Cyclic AMP levels in islets were not affected by DL-glyceraldehyde. When DL-glyceraldehyde was added to the medium with glucose, significant inhibition of glucos-induced insulin release in its early phase was observed without the reduction of cyclic AMP levels in islets. From these findings, the following possibilities are suggested and discussed. 1. Maintenance of the cyclic AMP levels in islets is a necessary but insufficient condition for glucose-induced insulin release particularly for its early phase. 2. Glucose-induced insulin release seems to depend on both the binding of glucose with glucoreceptor and the supply of some metabolites. Mannoheptulose inhibits both mechanisms. DL-glyceraldehyde may supply metabolites but competitively inhibit the binding of glucose to the glucoreceptor."}
{"id": "PMID:188635", "title": "Endocrine function in a case of beta-adrenergic hyperdynamic circulatory state.", "content": "Endocrine functions were investigated in a case of \"beta-adrenergic hyperdynamic circulatory state\". This state was diagnosed by (1) typical symptoms of cardiac awareness, (2) physical findings (increments of pulse rate and blood pressure by changing positions or walking), (3) increase in cardiac output (5.25 l/min leads to 14.03 l/min) and decrease in circulatory time (10.8 sec leads to 5.5 sec) by isoproterenol infusion (0.02 mug/min/kg body weight), (4) rapid loss of symptoms and above findings by propranolol treatment (30 mg per os daily) and reappearance by discontinuing medication. The mechanism of insulin response to glucose has been a controversy as to whether the secretion is transmitted by beta-receptor or independent glucose receptor. And in this physiologic beta-adrenergic state, it was found that insulin responses in IVGTT and OGTT were within normal limit. When beta-adrenergic condition was corrected by propranolol treatment, insulin responses were shown lowered, though in the normal range. This could be reproduced by discontinuing medication. Insulin, glucagon and growth hormone secretions caused by arginine were also found normal, but during the period the patient was on propranolol therapy, all responses were decreased, within the normal range. These results do not positively support the idea that glucose receptor is linked to beta-receptor. They do not either agree with the contention that secretions of insulin, glucagon and growth hormone induced by arginine are mediated through beta-receptors.", "contents": "Endocrine function in a case of beta-adrenergic hyperdynamic circulatory state. Endocrine functions were investigated in a case of \"beta-adrenergic hyperdynamic circulatory state\". This state was diagnosed by (1) typical symptoms of cardiac awareness, (2) physical findings (increments of pulse rate and blood pressure by changing positions or walking), (3) increase in cardiac output (5.25 l/min leads to 14.03 l/min) and decrease in circulatory time (10.8 sec leads to 5.5 sec) by isoproterenol infusion (0.02 mug/min/kg body weight), (4) rapid loss of symptoms and above findings by propranolol treatment (30 mg per os daily) and reappearance by discontinuing medication. The mechanism of insulin response to glucose has been a controversy as to whether the secretion is transmitted by beta-receptor or independent glucose receptor. And in this physiologic beta-adrenergic state, it was found that insulin responses in IVGTT and OGTT were within normal limit. When beta-adrenergic condition was corrected by propranolol treatment, insulin responses were shown lowered, though in the normal range. This could be reproduced by discontinuing medication. Insulin, glucagon and growth hormone secretions caused by arginine were also found normal, but during the period the patient was on propranolol therapy, all responses were decreased, within the normal range. These results do not positively support the idea that glucose receptor is linked to beta-receptor. They do not either agree with the contention that secretions of insulin, glucagon and growth hormone induced by arginine are mediated through beta-receptors."}
{"id": "PMID:188636", "title": "Lack of a direct effect of homocysteic acid on growth hormone and prolactin receptors.", "content": "The effects of homoystine derivatives upon GH and prolactin receptors which are reported to stimulate growth in the rat were investigated. Several concentrations of homocysteic acid, homocysteine, homocysteinethiolactone, homoystine as well as other amino-acids were used in GH and prolactin receptor assay systems to determine their growth promoting or the lactogenic activities. None of the aminoacids used displaced labelled hGH or ovine PRL. It os concluded that derivatives of homoystine stimulate growth by an indirect mechanism and exhibit a lack of a direct stimulation of GH and prolactin receptors.", "contents": "Lack of a direct effect of homocysteic acid on growth hormone and prolactin receptors. The effects of homoystine derivatives upon GH and prolactin receptors which are reported to stimulate growth in the rat were investigated. Several concentrations of homocysteic acid, homocysteine, homocysteinethiolactone, homoystine as well as other amino-acids were used in GH and prolactin receptor assay systems to determine their growth promoting or the lactogenic activities. None of the aminoacids used displaced labelled hGH or ovine PRL. It os concluded that derivatives of homoystine stimulate growth by an indirect mechanism and exhibit a lack of a direct stimulation of GH and prolactin receptors."}
{"id": "PMID:188637", "title": "Effect of hypophysectomy on responsiveness of rat adrenal slices to ACTH--pregnenolone formation from endogenous cholesterol.", "content": "Responsiveness of rat adrenal slices to ACTH was studied by measuring pregnenolone formation from endogenous cholesterol. The yield of pregnenolone by adrenal slices of hypophysectomized for 48 hrs rats was markedly higher as compared to intact animals.", "contents": "Effect of hypophysectomy on responsiveness of rat adrenal slices to ACTH--pregnenolone formation from endogenous cholesterol. Responsiveness of rat adrenal slices to ACTH was studied by measuring pregnenolone formation from endogenous cholesterol. The yield of pregnenolone by adrenal slices of hypophysectomized for 48 hrs rats was markedly higher as compared to intact animals."}
{"id": "PMID:188640", "title": "7-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-L-glycero-D-manno-heptose. A constituent of the endotoxin of Bordetella pertussis.", "content": "Hydrolysis of the Bordetella pertussis endotoxin, extracted from both \"phase I\" and \"phase IV\" bacteria, with 4 M HCl for 1 h at 100 degrees C, released the disaccharide named in the title; it was isolated by paper electrophoresis or by ion-exchange chromatography in about 1% yield (w/w). The structure of the heptose could be rigorously established by chemical degradation; the facts that the glucosaminidic linkage was hydrolysed by an enzyme preparation containing both, alpha and beta-N-acetylglucosaminidase activities, whereas it was resistant to cleavage by pure beta-N-acetylglucosaminidase strongly support the assumption that the disaccharide contains an alpha-D-glucosaminide linkage.", "contents": "7-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-L-glycero-D-manno-heptose. A constituent of the endotoxin of Bordetella pertussis. Hydrolysis of the Bordetella pertussis endotoxin, extracted from both \"phase I\" and \"phase IV\" bacteria, with 4 M HCl for 1 h at 100 degrees C, released the disaccharide named in the title; it was isolated by paper electrophoresis or by ion-exchange chromatography in about 1% yield (w/w). The structure of the heptose could be rigorously established by chemical degradation; the facts that the glucosaminidic linkage was hydrolysed by an enzyme preparation containing both, alpha and beta-N-acetylglucosaminidase activities, whereas it was resistant to cleavage by pure beta-N-acetylglucosaminidase strongly support the assumption that the disaccharide contains an alpha-D-glucosaminide linkage."}
{"id": "PMID:188641", "title": "Characterization of the amino-terminal segment in type III procollagen.", "content": "Native type III collagen and procollagen were prepared from fetal bovine skin. Examination of the cleavage products produced by digestion with tadpole collagenase demonstrated that the three palpha1(III) chains of type III procollagen were linked together by disulfide bonds occurring at both the amino-terminal and carboxy-terminal portions of the molecule. Type III collagen contained interchain disulfide bonds only in the carboxy-terminal region of the molecule. After digestion of procollagen with bacterial collagenase an amino-terminal, triple-stranded peptide fragment was isolated. The reduced and alkylated chain constituents of this fragment had molecular weights of about 21 000. After digestion of procollagen with cyanogen bromide a related triple-stranded fragment was isolated. The chains of the cyanogen bromide fragment had a molecular weight of about 27 000. When the collagenase-derived peptide was fully reduced and alkylated, it became susceptible to further digestion with bacterial collagenase. This treatment released a fragment of about 97 amino acid residues which contained 12 cystein residues and had an amino acid composition typical for globular proteins. A second, non-helical fragment of about 48 amino acid residues contained three cysteines. This latter fragment is formed from sequences that overlap the amino-terminal region in the collagen alpha1(III) chain by 20 amino acids and possesses an antigenic determinant specific for the alpha1(III) chain. The collagenase-sensitive region exposed by reduction comprised about 33 amino acid residues. It was recovered as a mixture of small peptides. These results indicate that the amino-terminal region of type III procollagen has the same type of structure as the homologous region of type I procollagen. It consists of a globular, a collagen-like and a non-helical domain. Interchain disulfide bonding and the occurrence of cysteines in the non-helical domain are, however, unique for type III procollagen.", "contents": "Characterization of the amino-terminal segment in type III procollagen. Native type III collagen and procollagen were prepared from fetal bovine skin. Examination of the cleavage products produced by digestion with tadpole collagenase demonstrated that the three palpha1(III) chains of type III procollagen were linked together by disulfide bonds occurring at both the amino-terminal and carboxy-terminal portions of the molecule. Type III collagen contained interchain disulfide bonds only in the carboxy-terminal region of the molecule. After digestion of procollagen with bacterial collagenase an amino-terminal, triple-stranded peptide fragment was isolated. The reduced and alkylated chain constituents of this fragment had molecular weights of about 21 000. After digestion of procollagen with cyanogen bromide a related triple-stranded fragment was isolated. The chains of the cyanogen bromide fragment had a molecular weight of about 27 000. When the collagenase-derived peptide was fully reduced and alkylated, it became susceptible to further digestion with bacterial collagenase. This treatment released a fragment of about 97 amino acid residues which contained 12 cystein residues and had an amino acid composition typical for globular proteins. A second, non-helical fragment of about 48 amino acid residues contained three cysteines. This latter fragment is formed from sequences that overlap the amino-terminal region in the collagen alpha1(III) chain by 20 amino acids and possesses an antigenic determinant specific for the alpha1(III) chain. The collagenase-sensitive region exposed by reduction comprised about 33 amino acid residues. It was recovered as a mixture of small peptides. These results indicate that the amino-terminal region of type III procollagen has the same type of structure as the homologous region of type I procollagen. It consists of a globular, a collagen-like and a non-helical domain. Interchain disulfide bonding and the occurrence of cysteines in the non-helical domain are, however, unique for type III procollagen."}
{"id": "PMID:188642", "title": "Interaction of the apoproteins of very low density and high density lipoproteins with synthetic phospholipids.", "content": "The interaction of synthetic dimyristoyl phosphatidylcholine (lecithin) liposomes with isolated apoC-I and apoC-III proteins from very low density lipoproteins has been studied by microcalorimetry. Complex formation is a highly exothermal process characterized by a maximal enthalpy of -130 kcal/mol (-544 kJ) apoC-III-1 and -65 kcal/mol apoC-I proteins (-272 kJ). The complex composition determined after its isolation by ultracentrifugal flotation agrees with the value derived from the enthalpy binding curves. The binding of a constant amount of dimyristoyl lecithin to apoprotein mixtures containing various proportions of apoA-I and apoC-III failed to demonstrate the existence of any preferential association between the two apoproteins, in contrast with results obtained previously with apoA-I/apoA-II protein mixtures. Finally the various contributions to the enthalpy of binding such as that arising from an increase in apoprotein helicity have been evaluated. A classification of the apolipoproteins according to their lipid-binding affinity is proposed as: apoA-II congruent to apoC-III greater than apoC-I greater than apoA-I proteins.", "contents": "Interaction of the apoproteins of very low density and high density lipoproteins with synthetic phospholipids. The interaction of synthetic dimyristoyl phosphatidylcholine (lecithin) liposomes with isolated apoC-I and apoC-III proteins from very low density lipoproteins has been studied by microcalorimetry. Complex formation is a highly exothermal process characterized by a maximal enthalpy of -130 kcal/mol (-544 kJ) apoC-III-1 and -65 kcal/mol apoC-I proteins (-272 kJ). The complex composition determined after its isolation by ultracentrifugal flotation agrees with the value derived from the enthalpy binding curves. The binding of a constant amount of dimyristoyl lecithin to apoprotein mixtures containing various proportions of apoA-I and apoC-III failed to demonstrate the existence of any preferential association between the two apoproteins, in contrast with results obtained previously with apoA-I/apoA-II protein mixtures. Finally the various contributions to the enthalpy of binding such as that arising from an increase in apoprotein helicity have been evaluated. A classification of the apolipoproteins according to their lipid-binding affinity is proposed as: apoA-II congruent to apoC-III greater than apoC-I greater than apoA-I proteins."}
{"id": "PMID:188643", "title": "Uridine-diphosphate-glucose 4-epimerase from Saccharomyces fragilis. Inactivation by heat and reconstitution of the inactive enzyme.", "content": "UDP-glucose 4-epimerase from Saccharomyces fragilis is rapidly inactivated by heating at 42 degrees C for 7 min and at 45 degrees C for 4 min. The effector site, specific for sugar phosphates, is destroyed still earlier. The enzyme is inactivated by the dissocation of NAD from it leaving the dimeric structure unaffected. It can be reactivated by mercaptoethanol and NAD, both of which are essential for reactivation, and NAD becomes associated with the dimeric protein moiety.", "contents": "Uridine-diphosphate-glucose 4-epimerase from Saccharomyces fragilis. Inactivation by heat and reconstitution of the inactive enzyme. UDP-glucose 4-epimerase from Saccharomyces fragilis is rapidly inactivated by heating at 42 degrees C for 7 min and at 45 degrees C for 4 min. The effector site, specific for sugar phosphates, is destroyed still earlier. The enzyme is inactivated by the dissocation of NAD from it leaving the dimeric structure unaffected. It can be reactivated by mercaptoethanol and NAD, both of which are essential for reactivation, and NAD becomes associated with the dimeric protein moiety."}
{"id": "PMID:188644", "title": "Protein degradation during yeast sporulation. Enzyme and cytochrome patterns.", "content": "The levels of several enzymes have been studied during sporulation of Saccharomyces cerevisia. The specific activities of ribonuclease and aminopeptidase I raised several-fold after transfer of the cells to sporulation medium, whereas the specific activities of phosphofructokinase, glucose-6-phosphate dehydrogenase, tryptophan synthase and pyruvate decarboxylase were not significantly altered. The specific activities of NAD-dependent glutamate dehydrogenase, isocitrate lyase, malate dehydrogenase and fructose bisphosphatase all decreased from the onset of sporulation. The inactivation of these latter enzymes was inhibited by cycloheximide and by inhibitors of energy metabolism. Hexokinase, alcohol dehydrogenase and glutamate oxaloacetate transaminase were partially lost from the cells during the period of ascus maturation. None of the enzyme changes observed proved to be 'sporulation-specific' in that it occurred exclusively in sporulating diploid yeast cells. Therefore it is postulated that the meiotic events and the metabolic changes required for ascospore formation are under separate genetic control in this organism. During sporulation, the cellular content of cytochromes b, c, and aa3 was reduced to 20% or less of that present in vegetative derepressed cells. Since the relative percentage of total to cycloheximide-insensitive mitochondrial protein synthesis was not significantly altered throughout sporulation, and the pattern of mitochondrially synthesized polypeptides was rather similar both in vegetative and in sporulating cells, it appeared that not only degradation but also synthesis and therefore turnover of the mitochondrially coded polypeptides of cytochromes b and aa3 took place during sporulation. The activity ratio of cytochrome c oxidase to F1-ATPase in submitochondrial particles isolated from vegetative cells and from purified asci was almost identical. This indicates that the loss of membrane-bound mitochondrial cytochromes during sporulation is probably due to a nonselective degradation of inner mitochondrial membrane proteins.", "contents": "Protein degradation during yeast sporulation. Enzyme and cytochrome patterns. The levels of several enzymes have been studied during sporulation of Saccharomyces cerevisia. The specific activities of ribonuclease and aminopeptidase I raised several-fold after transfer of the cells to sporulation medium, whereas the specific activities of phosphofructokinase, glucose-6-phosphate dehydrogenase, tryptophan synthase and pyruvate decarboxylase were not significantly altered. The specific activities of NAD-dependent glutamate dehydrogenase, isocitrate lyase, malate dehydrogenase and fructose bisphosphatase all decreased from the onset of sporulation. The inactivation of these latter enzymes was inhibited by cycloheximide and by inhibitors of energy metabolism. Hexokinase, alcohol dehydrogenase and glutamate oxaloacetate transaminase were partially lost from the cells during the period of ascus maturation. None of the enzyme changes observed proved to be 'sporulation-specific' in that it occurred exclusively in sporulating diploid yeast cells. Therefore it is postulated that the meiotic events and the metabolic changes required for ascospore formation are under separate genetic control in this organism. During sporulation, the cellular content of cytochromes b, c, and aa3 was reduced to 20% or less of that present in vegetative derepressed cells. Since the relative percentage of total to cycloheximide-insensitive mitochondrial protein synthesis was not significantly altered throughout sporulation, and the pattern of mitochondrially synthesized polypeptides was rather similar both in vegetative and in sporulating cells, it appeared that not only degradation but also synthesis and therefore turnover of the mitochondrially coded polypeptides of cytochromes b and aa3 took place during sporulation. The activity ratio of cytochrome c oxidase to F1-ATPase in submitochondrial particles isolated from vegetative cells and from purified asci was almost identical. This indicates that the loss of membrane-bound mitochondrial cytochromes during sporulation is probably due to a nonselective degradation of inner mitochondrial membrane proteins."}
{"id": "PMID:188645", "title": "The cytochrome bc) complex of yeast mitochondria. Site of translation of the polypeptides in vivo.", "content": "1. Yeast cells were labelled with radioactive amino acids in the presence of cycloheximide and the cytochrome bc1 complex was isolated from them as described in the preceding paper (Katan, M.B.., Pool, L. & Groot, G.S.P. (1976)Eur. J. Biochem, 65, 95-105). After analysis of this preparation by sodium dodecylsulphate polyacrylamide gel electrophoresis only one band, with an apparent Mr of 32000, was found to have incorporated radioactivity. The amount of label in the band was low, but could be increased approximately 5-fold by preincubating the cells in erythromycin before the labelling period. 2. Cells were labelled in the presence of chloramphenicol and the cytochrome bc1 complex was isolated by (NH4)2SO4 fractionation. Upon electrophoresis in the presence of sodium dodecylsulphate only four of the six bands that belong to the complex were found to have incorporated radioactivity; no radioactivity was found in the bands with an Mr of 40000 and 17000. The same result was obtained after labelling in the presence of acriflavin. If, however, the cytochrome bc1 complex was isolated by immunoprecipitation, all bands were found to have incorporated radioactivity in the presence of chloramphenicol. The amount of radioactivity in the Mr 32000 band was now clearly depressed. 3. It is concluded that of the seven polypeptides of the cytochrome bc1 complex of yeast only one is made on mitochondrial ribosomes. This polypeptide has an Mr of 32000 and is probably associated with cytochrome b.", "contents": "The cytochrome bc) complex of yeast mitochondria. Site of translation of the polypeptides in vivo. 1. Yeast cells were labelled with radioactive amino acids in the presence of cycloheximide and the cytochrome bc1 complex was isolated from them as described in the preceding paper (Katan, M.B.., Pool, L. & Groot, G.S.P. (1976)Eur. J. Biochem, 65, 95-105). After analysis of this preparation by sodium dodecylsulphate polyacrylamide gel electrophoresis only one band, with an apparent Mr of 32000, was found to have incorporated radioactivity. The amount of label in the band was low, but could be increased approximately 5-fold by preincubating the cells in erythromycin before the labelling period. 2. Cells were labelled in the presence of chloramphenicol and the cytochrome bc1 complex was isolated by (NH4)2SO4 fractionation. Upon electrophoresis in the presence of sodium dodecylsulphate only four of the six bands that belong to the complex were found to have incorporated radioactivity; no radioactivity was found in the bands with an Mr of 40000 and 17000. The same result was obtained after labelling in the presence of acriflavin. If, however, the cytochrome bc1 complex was isolated by immunoprecipitation, all bands were found to have incorporated radioactivity in the presence of chloramphenicol. The amount of radioactivity in the Mr 32000 band was now clearly depressed. 3. It is concluded that of the seven polypeptides of the cytochrome bc1 complex of yeast only one is made on mitochondrial ribosomes. This polypeptide has an Mr of 32000 and is probably associated with cytochrome b."}
{"id": "PMID:188646", "title": "Separation and characterization of two phosphorylase phosphatase inhibitors from rabbit skeletal muscle.", "content": "Two heat-stable and trypsin-labile inhibitors of phosphorylase phosphatase, designated inhibitor-1 and inhibitor-2, were partially purified from extracts of rabbit skeletal muscle by heating and coloumn chromatography using DEAE-dellulose and Bio-gel P-60. Inhibitor-1 exists in an active phosphorylated form and an inactive dephosphorylated form. The interconversion of phosphorylated inhibitor-1 and dephosphorylated inhibitor-1 is mediated by protein kinase dependent on adenosine 3':5'-monophosphate (cyclic AMP) and a Mn2+-stimulated phosphoprotein phosphatase. Inhibitory activity of inhibitor-2 is not influenced by treatment with either the kinase or the Mn2+-stimulated phosphatase. The molecular weights of inhibitor-1 and inhibitor-2 estimated by sodium dodecylsulfate-polyacrylamide gel electrophoresis are 26000 and 33000 respectively. Both inhibitor-1 and inhibitor-2 inhibit phosphorylase phosphatase by a mechanism which appears to be non-competitive with respect to the substrate phosphorylase a. Inhibitor fractions at early stages of purification also inhibit cyclic-AMP-dependent histone phosphorylation, but this kinase inhibitory activity resides with a protein moiety which is separable from inhibitor-1 and inhibitor-2.", "contents": "Separation and characterization of two phosphorylase phosphatase inhibitors from rabbit skeletal muscle. Two heat-stable and trypsin-labile inhibitors of phosphorylase phosphatase, designated inhibitor-1 and inhibitor-2, were partially purified from extracts of rabbit skeletal muscle by heating and coloumn chromatography using DEAE-dellulose and Bio-gel P-60. Inhibitor-1 exists in an active phosphorylated form and an inactive dephosphorylated form. The interconversion of phosphorylated inhibitor-1 and dephosphorylated inhibitor-1 is mediated by protein kinase dependent on adenosine 3':5'-monophosphate (cyclic AMP) and a Mn2+-stimulated phosphoprotein phosphatase. Inhibitory activity of inhibitor-2 is not influenced by treatment with either the kinase or the Mn2+-stimulated phosphatase. The molecular weights of inhibitor-1 and inhibitor-2 estimated by sodium dodecylsulfate-polyacrylamide gel electrophoresis are 26000 and 33000 respectively. Both inhibitor-1 and inhibitor-2 inhibit phosphorylase phosphatase by a mechanism which appears to be non-competitive with respect to the substrate phosphorylase a. Inhibitor fractions at early stages of purification also inhibit cyclic-AMP-dependent histone phosphorylation, but this kinase inhibitory activity resides with a protein moiety which is separable from inhibitor-1 and inhibitor-2."}
{"id": "PMID:188647", "title": "Metabolic regulation of steroidogenesis in isolated adrenal cells of rat. Relationship of adrenocorticotropin-, adenosine 3':5'-monophosphate-and guanosine 3':5'-monophosphate-stimulated steroidogenesis with the activation of protein kinase.", "content": "The data presented with the isolated adrenal cells, in the present study, show that adrenocorticotropin in the physiological concentration range stimulates the synthesis of guanosine 3':5'-monophosphate(cyclic GMP), protein kinase activity, and steroidogenesis in a concentration-dependent manner without detectable rise in the levels of adenosine 3':5'-monophosphate (cyclic AMP). Millimolar concentrations of cyclic AMP and cyclic GMP, which stimulate corticosterone synthesis, also activate kinase activity and steroidogenesis in a sigmoid concentration-response manner. The process of phosphorylation activated by corticotropin, cyclic AMP and cyclic GMP is not inhibited by cycloheximide or actinomyin D. It is therefore proposed that the hormonal responses mediated by cyclic GMP and cyclic AMP are via the protein kinase enzymatic steps, and the inhibitory effect of cycloheximide and actinomycin D in corticotropin-stimulated steroidogenesis follows this step. In conjuction with our previous observations that the biosynthetic steps from (20S)-20-hydroxycholesterol to corticosterone are neither inhibited by cycloheximide nor affected by cyclic GMP, it is inferred that the rate-limiting step of adrenal steroidogenesis is the transformation of cholesterol to (20S)-20hydroxycholesterol and this very step is regulated by cyclic GMP and cyclic AMP. Of further significance are the findings that micromolar cincentrations of cyclic AMP and cyclic GMP, which do not stimulate steroidogenesis, effectively stimulate protein kinase activity in a concentration-dependent manner. It is therefore concluded that all cyclic-nucleotide-dependent protein kinase activities of the cell are not necessarily related to steroidogenesis.", "contents": "Metabolic regulation of steroidogenesis in isolated adrenal cells of rat. Relationship of adrenocorticotropin-, adenosine 3':5'-monophosphate-and guanosine 3':5'-monophosphate-stimulated steroidogenesis with the activation of protein kinase. The data presented with the isolated adrenal cells, in the present study, show that adrenocorticotropin in the physiological concentration range stimulates the synthesis of guanosine 3':5'-monophosphate(cyclic GMP), protein kinase activity, and steroidogenesis in a concentration-dependent manner without detectable rise in the levels of adenosine 3':5'-monophosphate (cyclic AMP). Millimolar concentrations of cyclic AMP and cyclic GMP, which stimulate corticosterone synthesis, also activate kinase activity and steroidogenesis in a sigmoid concentration-response manner. The process of phosphorylation activated by corticotropin, cyclic AMP and cyclic GMP is not inhibited by cycloheximide or actinomyin D. It is therefore proposed that the hormonal responses mediated by cyclic GMP and cyclic AMP are via the protein kinase enzymatic steps, and the inhibitory effect of cycloheximide and actinomycin D in corticotropin-stimulated steroidogenesis follows this step. In conjuction with our previous observations that the biosynthetic steps from (20S)-20-hydroxycholesterol to corticosterone are neither inhibited by cycloheximide nor affected by cyclic GMP, it is inferred that the rate-limiting step of adrenal steroidogenesis is the transformation of cholesterol to (20S)-20hydroxycholesterol and this very step is regulated by cyclic GMP and cyclic AMP. Of further significance are the findings that micromolar cincentrations of cyclic AMP and cyclic GMP, which do not stimulate steroidogenesis, effectively stimulate protein kinase activity in a concentration-dependent manner. It is therefore concluded that all cyclic-nucleotide-dependent protein kinase activities of the cell are not necessarily related to steroidogenesis."}
{"id": "PMID:188648", "title": "Purification of poly(ADP-ribose) polymerase from Ehrlich ascites tumor cells by chromatography on DNA-agarose.", "content": "Poly(ADP-ribose) polymerase with a high specific activity was obtained from Ehrlich ascites tumor cells by extraction of nuclei with 175 mM potassium phosphate, followed by chromatography on DNA-agarose. Electrophoretic analysis indicated that the preparation contained two proteins, one of which was shown to catalyze the synthesis of poly(ADP-ribose). As expected from results obtained by other workers, the synthesis was inhibited by nicotinamide and thymidine, and stimulated by DNA. Addition of histones gave inhibition of the synthesis, unless DNA was present in the reaction mixture.", "contents": "Purification of poly(ADP-ribose) polymerase from Ehrlich ascites tumor cells by chromatography on DNA-agarose. Poly(ADP-ribose) polymerase with a high specific activity was obtained from Ehrlich ascites tumor cells by extraction of nuclei with 175 mM potassium phosphate, followed by chromatography on DNA-agarose. Electrophoretic analysis indicated that the preparation contained two proteins, one of which was shown to catalyze the synthesis of poly(ADP-ribose). As expected from results obtained by other workers, the synthesis was inhibited by nicotinamide and thymidine, and stimulated by DNA. Addition of histones gave inhibition of the synthesis, unless DNA was present in the reaction mixture."}
{"id": "PMID:188649", "title": "Subunit structure of simian-virus-40 minichromosome.", "content": "Electron microscopic evidence indicates that Simian virus 40 (SV40) minichromosomes extracted from infected cells consist of 20 +/- 2 nucleosomes, each containing 190 -- 200 base pairs of DNA. About 50% of the nucleosomes are not close together, but connected by segments of DNA of irregular lengths which correspond to about 15% of the viral genome, irrespective of the ionic strength. Micrococcal nuclease digestion studies show that there is about 200 base pairs of DNA in the biochemical unit of SV40 chromatin. Therefore, the visible internucleosomal DNA of the SV40 minichromosome does not arise from an unfolding of a fraction of the 190 - 200 base pairs of DNA initially wound in the nucleosome. These results support the chromatin model which proposes that the same DNA length is contained in the nucleosome and the biochemical unit. Results from extensive micrococcal nuclease digestion suggest that an SV40 nucleosome consists of a 'core' containing a DNA segment of about 135 base pairs associated to a DNA fragment more susceptible to nuclease attack. The addition of histone H1 results in a striking condensation of the SV40 minichromosome, which supports the assumption that histone H1 is involved in the folding of chromatin fibers.", "contents": "Subunit structure of simian-virus-40 minichromosome. Electron microscopic evidence indicates that Simian virus 40 (SV40) minichromosomes extracted from infected cells consist of 20 +/- 2 nucleosomes, each containing 190 -- 200 base pairs of DNA. About 50% of the nucleosomes are not close together, but connected by segments of DNA of irregular lengths which correspond to about 15% of the viral genome, irrespective of the ionic strength. Micrococcal nuclease digestion studies show that there is about 200 base pairs of DNA in the biochemical unit of SV40 chromatin. Therefore, the visible internucleosomal DNA of the SV40 minichromosome does not arise from an unfolding of a fraction of the 190 - 200 base pairs of DNA initially wound in the nucleosome. These results support the chromatin model which proposes that the same DNA length is contained in the nucleosome and the biochemical unit. Results from extensive micrococcal nuclease digestion suggest that an SV40 nucleosome consists of a 'core' containing a DNA segment of about 135 base pairs associated to a DNA fragment more susceptible to nuclease attack. The addition of histone H1 results in a striking condensation of the SV40 minichromosome, which supports the assumption that histone H1 is involved in the folding of chromatin fibers."}
{"id": "PMID:188650", "title": "A new plant-type ferredoxin from halobacteria.", "content": "A stable, 2Fe-type ferredoxin has been prepared from Halobacterium halobium and purified by chromatography. A similar ferredoxin was also found in three other Halobacteria. The ferredoxin is present in large amounts-about 1 percent of the total soluble protein. From amino acid composition a molecular weight of 14800 +/- 200 was calculated. The ferredoxin was found to contain two atoms each of iron and sulphide. The midpoint redox potential of the protein is about -345 mV. The electron paramagnetic resonance spectrum of the reduced form shows much similarity to plant and algal ferredoxins with gx = 1.90, gy = 1.97 and gz = 2.07. The same similarity is observed in the optical absorption, optical rotatory dispersion and circular dichroism spectra. However it does not seem to mediate electron transport in the NADP-photoreduction system of chloroplasts. Extracts of the bacterial cells catalyze the reduction of the ferredoxin by NADH.", "contents": "A new plant-type ferredoxin from halobacteria. A stable, 2Fe-type ferredoxin has been prepared from Halobacterium halobium and purified by chromatography. A similar ferredoxin was also found in three other Halobacteria. The ferredoxin is present in large amounts-about 1 percent of the total soluble protein. From amino acid composition a molecular weight of 14800 +/- 200 was calculated. The ferredoxin was found to contain two atoms each of iron and sulphide. The midpoint redox potential of the protein is about -345 mV. The electron paramagnetic resonance spectrum of the reduced form shows much similarity to plant and algal ferredoxins with gx = 1.90, gy = 1.97 and gz = 2.07. The same similarity is observed in the optical absorption, optical rotatory dispersion and circular dichroism spectra. However it does not seem to mediate electron transport in the NADP-photoreduction system of chloroplasts. Extracts of the bacterial cells catalyze the reduction of the ferredoxin by NADH."}
{"id": "PMID:188651", "title": "A spin-label study of the chromaffin granule membrane.", "content": "The structure of the chromaffin granule membrane has been probed using a number of different spin labels. Both the effect of temperature and high levels of calcium have been studied. 1. The results from three positional isomers of the stearic acid spin label demonstrate that a substantial part of the membrane lipid (that is sensed by the probe) is in a bilayer structure which undergoes a structural transition at 32-36 degrees C, characterized by an increase in the population of gauche isomers in the lipid chains. A possible mechanism for this transition would be the preferential segregation of cholesterol. 2. The covalently bound iodoacetamide spin label reveals a transition within the protein component of the membrane or its immediate lipid environment at 32 degrees C. This transition corresponds to an increased degree of motional freedom of the spin label above the transition temperature. 3. The lipid-soluble spin label 2,2,6,6-tetramethyl-piperidine-1-oxyl exhibits a break at 34 degrees C in the temperature-dependence of its partitioning into the membrane. This could correspond to the onset of a lateral separation in the membrane lipid, again possible involving a re-distribution of cholesterol. 4. Calcium abolishes, diminishes or shifts the transition observed by the spin label and decreases the amplitude of motion of the stearic acid spin labels, again possibly involving a redistribution of cholesterol and also lysolecithin. The temperatures of the structural transition agree well with the changes in the enzymic activity of the membrane ATPase and NADH oxidase functions and also with the results from fluorescent probes [Bashford et al., Eur. J. Biochem. 67, 105-114(1976)]. It is possible that triggering of the transition either by calcium or some other stimulus may play a role in catecholamine release and membrane fusion.", "contents": "A spin-label study of the chromaffin granule membrane. The structure of the chromaffin granule membrane has been probed using a number of different spin labels. Both the effect of temperature and high levels of calcium have been studied. 1. The results from three positional isomers of the stearic acid spin label demonstrate that a substantial part of the membrane lipid (that is sensed by the probe) is in a bilayer structure which undergoes a structural transition at 32-36 degrees C, characterized by an increase in the population of gauche isomers in the lipid chains. A possible mechanism for this transition would be the preferential segregation of cholesterol. 2. The covalently bound iodoacetamide spin label reveals a transition within the protein component of the membrane or its immediate lipid environment at 32 degrees C. This transition corresponds to an increased degree of motional freedom of the spin label above the transition temperature. 3. The lipid-soluble spin label 2,2,6,6-tetramethyl-piperidine-1-oxyl exhibits a break at 34 degrees C in the temperature-dependence of its partitioning into the membrane. This could correspond to the onset of a lateral separation in the membrane lipid, again possible involving a re-distribution of cholesterol. 4. Calcium abolishes, diminishes or shifts the transition observed by the spin label and decreases the amplitude of motion of the stearic acid spin labels, again possibly involving a redistribution of cholesterol and also lysolecithin. The temperatures of the structural transition agree well with the changes in the enzymic activity of the membrane ATPase and NADH oxidase functions and also with the results from fluorescent probes [Bashford et al., Eur. J. Biochem. 67, 105-114(1976)]. It is possible that triggering of the transition either by calcium or some other stimulus may play a role in catecholamine release and membrane fusion."}
{"id": "PMID:188652", "title": "Isolation and characterization of hydrophobic proteins (H proteins) in the membrane fraction of Bacillus subtilis. Involvement in membrane biosynthesis and the formation of biochemically active membrane vesicles by combining H proteins with lipid.", "content": "Cytoplasmic membranes of Bacillus subtilis, grown in complex medium containing glucose, were fractionated into three membrane subfractions [light band (1.155 - 1.158 g/cm3); medium band (1.181 - 1.183 g/cm3); heavy band (1.21 - 1.25 g/cm3)] by sucrose density gradient centrifugation. Among these subfractions, the light and medium bands consisted mainly of membranes but the heavy band consisted of an irregular arrangement or aggregate of small globular protein components of 5 - 8 nm in diameter. We named this H-protein. H-protein formed trilamellar unit membrane structure when combined with lipid. In pulse-labeling and pulse-chase experiments with radioactive leucine, it was found that H-protein consisted of the newest membrane protein synthesized in the cells and the label incorporated into H-protein was shifted into light and medium band of the membranes during the chase. Cytochromes were not found in H-protein. However, when H-protein was incubated with haem alpha and protohaem, these compounds were incorporated into the apoproteins of the cytochromes present in H-protein and form cytochromes a and b. Cytochromes were also formed in H-protein which were isolated from the cells grown in the presence of haemin (haemin-grown H protein). Succinate dehydrogenase activity was increased about 4-fold by combining H-protein or haemin-grown H protein with lipid. H-protein had no cytochrome oxidase activity; however, haemin-grown H protein was found to have some of the activity and this was increased about 4-fold by combining the protein with lipid. Haemin-grown H protein was also found to form succinate: cytochrome c oxidoreductase when combined with lipid and vitamin K2. On the other hand, succinate oxidase was required for the addition of lipid, vitamin K2 and cytochrome c. NADH oxidase was also found in haemin-grown H protein and was activated about 9-fold in constituted reaction systems. Vesicles formed by haemin-grown H protein and lipid, could accumulate alanine and proline by addition of NADH or reduced phenazine methosulfate. Alanine and proline was also accumulated into the vesicles when transport energy was supplied as a membrane potential introduced by K+-diffusion via valinomycin. These results would indicate that H-protein contains the apoprotein of cytochromes, and a carrier involved in the active transport of alanine and proline.", "contents": "Isolation and characterization of hydrophobic proteins (H proteins) in the membrane fraction of Bacillus subtilis. Involvement in membrane biosynthesis and the formation of biochemically active membrane vesicles by combining H proteins with lipid. Cytoplasmic membranes of Bacillus subtilis, grown in complex medium containing glucose, were fractionated into three membrane subfractions [light band (1.155 - 1.158 g/cm3); medium band (1.181 - 1.183 g/cm3); heavy band (1.21 - 1.25 g/cm3)] by sucrose density gradient centrifugation. Among these subfractions, the light and medium bands consisted mainly of membranes but the heavy band consisted of an irregular arrangement or aggregate of small globular protein components of 5 - 8 nm in diameter. We named this H-protein. H-protein formed trilamellar unit membrane structure when combined with lipid. In pulse-labeling and pulse-chase experiments with radioactive leucine, it was found that H-protein consisted of the newest membrane protein synthesized in the cells and the label incorporated into H-protein was shifted into light and medium band of the membranes during the chase. Cytochromes were not found in H-protein. However, when H-protein was incubated with haem alpha and protohaem, these compounds were incorporated into the apoproteins of the cytochromes present in H-protein and form cytochromes a and b. Cytochromes were also formed in H-protein which were isolated from the cells grown in the presence of haemin (haemin-grown H protein). Succinate dehydrogenase activity was increased about 4-fold by combining H-protein or haemin-grown H protein with lipid. H-protein had no cytochrome oxidase activity; however, haemin-grown H protein was found to have some of the activity and this was increased about 4-fold by combining the protein with lipid. Haemin-grown H protein was also found to form succinate: cytochrome c oxidoreductase when combined with lipid and vitamin K2. On the other hand, succinate oxidase was required for the addition of lipid, vitamin K2 and cytochrome c. NADH oxidase was also found in haemin-grown H protein and was activated about 9-fold in constituted reaction systems. Vesicles formed by haemin-grown H protein and lipid, could accumulate alanine and proline by addition of NADH or reduced phenazine methosulfate. Alanine and proline was also accumulated into the vesicles when transport energy was supplied as a membrane potential introduced by K+-diffusion via valinomycin. These results would indicate that H-protein contains the apoprotein of cytochromes, and a carrier involved in the active transport of alanine and proline."}
{"id": "PMID:188653", "title": "Difficulties in determining accurate molecular motion parameters from proton relaxation enhancement measurements as illustrated by the immunoglobulin G-Gd(III) system.", "content": "Longitudinal and traverse proton magnetic relaxation rates for water in the hydration sphere of Gd(III) bound to non-immune rabbit IgG (immunoglobulin G) have been determined over a wide range of frequencies (4-84 MHz) at constant temperature (19 degrees C) using pulsed nuclear magnetic resonance spectrometry. The rates have also been determined at temperatures between 0 and 40 degrees C for two frequencies (61 and 84 MHz). The rates were fitted to existing theory using a computer least-squares procedure. Further computer analysis was then carried out to determine the sensitivity of the best-fit error to variation in the variable parameters in the theoretical expressions used. These include the water co-ordination number (q) for which it was found large variations could occur (between approximately 2 and 8) for only small changes in the error of best-fit. It was concluded that a slow exchange contribution to the relaxation rates was important in deciding which parameters are poorly determined. A rotational correlation time (tau r) was obtained which suggested there might be considerable internal motion of the Fc region (C-terminal half of heavy-chain dimer) of the IgG molecule. However the possibility of large errors in this value prevented unequivocal conclusions being drawn.", "contents": "Difficulties in determining accurate molecular motion parameters from proton relaxation enhancement measurements as illustrated by the immunoglobulin G-Gd(III) system. Longitudinal and traverse proton magnetic relaxation rates for water in the hydration sphere of Gd(III) bound to non-immune rabbit IgG (immunoglobulin G) have been determined over a wide range of frequencies (4-84 MHz) at constant temperature (19 degrees C) using pulsed nuclear magnetic resonance spectrometry. The rates have also been determined at temperatures between 0 and 40 degrees C for two frequencies (61 and 84 MHz). The rates were fitted to existing theory using a computer least-squares procedure. Further computer analysis was then carried out to determine the sensitivity of the best-fit error to variation in the variable parameters in the theoretical expressions used. These include the water co-ordination number (q) for which it was found large variations could occur (between approximately 2 and 8) for only small changes in the error of best-fit. It was concluded that a slow exchange contribution to the relaxation rates was important in deciding which parameters are poorly determined. A rotational correlation time (tau r) was obtained which suggested there might be considerable internal motion of the Fc region (C-terminal half of heavy-chain dimer) of the IgG molecule. However the possibility of large errors in this value prevented unequivocal conclusions being drawn."}
{"id": "PMID:188654", "title": "Kinetic studies on a 4-methoxybenzoate O-demethylase from Pseudomonas putida.", "content": "A direct, sensitive and reliable photometric assay procedure for monitoring the activity of non-specific 4-methoxybenzoate O-demethylases of microorganisms is described. The assay is based on the O-demethylation of 3-nitro-4-methoxybenzoate to the yellow-coloured product 3-nitro-4-hydroxybenzoate. Using this assay and by monitoring the oxidation rate of reduced pyridine nucleotides, the kinetic properties of a purified, reconstituted enzyme system composed of 4-methoxybenzoate monooxygenase (O-demethylating) and a reductase from Pseudomonas putida have been investigated. It has been found that the KM value of the monoxygenase of this enzyme system towards different substrates (i.e. tight couplers, uncouplers and partial uncouplers) rises from the extremely low value of 0.07 muM for the tight couplers to about 55 muM for the uncouplers. The effect of possible inhibitors and metal ions on the reconstituted enzyme system was investigated. The inhibition pattern was almost identical to that found for the purified reductase, only batho-phenanthrolinedisulfonate showing a greater inhibition of the reconstituted enzyme system. The affinity of the reductase towards NADH was found to be approximately 200-fold greater than that towards NADPH. Futhermore, the affinity of this reductase to NADH depended on the nature of the electron acceptor. The affinity to NADH was more than 10 times higher when the monooxygenase-substrate complex was used as the electron acceptor, than when cytochrome c or 2,6-dichloroindophenol was used. These differences are discussed on the basis of enzyme-enzyme interactions between the reductase and the monooxygenase.", "contents": "Kinetic studies on a 4-methoxybenzoate O-demethylase from Pseudomonas putida. A direct, sensitive and reliable photometric assay procedure for monitoring the activity of non-specific 4-methoxybenzoate O-demethylases of microorganisms is described. The assay is based on the O-demethylation of 3-nitro-4-methoxybenzoate to the yellow-coloured product 3-nitro-4-hydroxybenzoate. Using this assay and by monitoring the oxidation rate of reduced pyridine nucleotides, the kinetic properties of a purified, reconstituted enzyme system composed of 4-methoxybenzoate monooxygenase (O-demethylating) and a reductase from Pseudomonas putida have been investigated. It has been found that the KM value of the monoxygenase of this enzyme system towards different substrates (i.e. tight couplers, uncouplers and partial uncouplers) rises from the extremely low value of 0.07 muM for the tight couplers to about 55 muM for the uncouplers. The effect of possible inhibitors and metal ions on the reconstituted enzyme system was investigated. The inhibition pattern was almost identical to that found for the purified reductase, only batho-phenanthrolinedisulfonate showing a greater inhibition of the reconstituted enzyme system. The affinity of the reductase towards NADH was found to be approximately 200-fold greater than that towards NADPH. Futhermore, the affinity of this reductase to NADH depended on the nature of the electron acceptor. The affinity to NADH was more than 10 times higher when the monooxygenase-substrate complex was used as the electron acceptor, than when cytochrome c or 2,6-dichloroindophenol was used. These differences are discussed on the basis of enzyme-enzyme interactions between the reductase and the monooxygenase."}
{"id": "PMID:188655", "title": "Glucose effect in tgl mutant of Escherichia col K12 defective in methyl-alpha-D-glucoside transport.", "content": "1. The dependence of the rate of accumulation of methyl-alpha-D-glucoside on its extracellular concentration was studied in the tgl mutant of Escherichia coli K12, isolated earlier. It has been shown that the kinetics of methyl-alpha-D-glucoside transport differ sharply from those in wild-type bacteria. 2. The beta-galactosidase synthesis in tgl strain is much less sensitive both to permanent and transient glucose catabolite repression. The level of cyclic AMP in mutant cells under the conditions of glucose catabolite repression is several times higher than in the parent strain. 3. The tgl mutation does not affect the manifestation of catabolite inhibition and inducer exclusion with glucose. 4. The data obtained are discussed in the light of a hypothesis concerning the existence of two sites, binding and pecific enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system. The tgl mutation alters the first site, and the second one is damaged by the pgt mutation. 5. It is suggested that the products of the tgl and gpt genes are necessary for the manifestation of the phenomena of glucose permanent and transient repression. The effects of catabolite inhibition and inducer exclusion are realized irrespective of the existence or absence of the tgl product.", "contents": "Glucose effect in tgl mutant of Escherichia col K12 defective in methyl-alpha-D-glucoside transport. 1. The dependence of the rate of accumulation of methyl-alpha-D-glucoside on its extracellular concentration was studied in the tgl mutant of Escherichia coli K12, isolated earlier. It has been shown that the kinetics of methyl-alpha-D-glucoside transport differ sharply from those in wild-type bacteria. 2. The beta-galactosidase synthesis in tgl strain is much less sensitive both to permanent and transient glucose catabolite repression. The level of cyclic AMP in mutant cells under the conditions of glucose catabolite repression is several times higher than in the parent strain. 3. The tgl mutation does not affect the manifestation of catabolite inhibition and inducer exclusion with glucose. 4. The data obtained are discussed in the light of a hypothesis concerning the existence of two sites, binding and pecific enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system. The tgl mutation alters the first site, and the second one is damaged by the pgt mutation. 5. It is suggested that the products of the tgl and gpt genes are necessary for the manifestation of the phenomena of glucose permanent and transient repression. The effects of catabolite inhibition and inducer exclusion are realized irrespective of the existence or absence of the tgl product."}
{"id": "PMID:188656", "title": "Binding studies of a spin-labelled oxidized coenzyme to bovine-liver glutamate dehydrogenase.", "content": "NAD+ with a nitroxide piperidine ring linked to the NH2 group of the adenine possesses full coenzymatic activity with glutamate dehydrogenase. Electron spin resonance spectra in the presence of glutamate dehydrogenase show mixtures of free and strongly immobilized spin-label. Binding studies in phosphate buffer demonstrate: (a) weak binary binding to the enzyme with a dissociation constant in the order of 2mM;(b) an indication for negative cooperativity or different sites for binding to enzyme-2-oxoglutarate, with dissociation constants in the order of 20--250muM; (c) similar but much weaker binding to enzyme-2-oxoglutarate-ADP; (d) a strong positive cooperative binding to enzyme-2-oxoglutarate-GTP, dependent on the enzyme concentration. Binding of phosphate to the enzyme with a Kd of about 20 mM or binding of pyrophosphate or tripolyphosphate with a Dd of about 2.5 mM enhances the binding of spin-labelled NAD+ in the presence of 2-oxoglutarate. There is evidence that the binding sites for these phosphates coincide with phosphate binding subsites of GTP.", "contents": "Binding studies of a spin-labelled oxidized coenzyme to bovine-liver glutamate dehydrogenase. NAD+ with a nitroxide piperidine ring linked to the NH2 group of the adenine possesses full coenzymatic activity with glutamate dehydrogenase. Electron spin resonance spectra in the presence of glutamate dehydrogenase show mixtures of free and strongly immobilized spin-label. Binding studies in phosphate buffer demonstrate: (a) weak binary binding to the enzyme with a dissociation constant in the order of 2mM;(b) an indication for negative cooperativity or different sites for binding to enzyme-2-oxoglutarate, with dissociation constants in the order of 20--250muM; (c) similar but much weaker binding to enzyme-2-oxoglutarate-ADP; (d) a strong positive cooperative binding to enzyme-2-oxoglutarate-GTP, dependent on the enzyme concentration. Binding of phosphate to the enzyme with a Kd of about 20 mM or binding of pyrophosphate or tripolyphosphate with a Dd of about 2.5 mM enhances the binding of spin-labelled NAD+ in the presence of 2-oxoglutarate. There is evidence that the binding sites for these phosphates coincide with phosphate binding subsites of GTP."}
{"id": "PMID:188657", "title": "Urinary cyclic AMP and renal concentrating capacity in infants.", "content": "In 15 infants between 1 and 31 weeks the effect of antidiuretic hormone (ADH) on the renal concentrating capacity and urinary cyclic AMP (cAMP) was tested. A significant decrease of urine flow and a significant increase of osmolality, urea and cAMP was observed indicating that the distal nephron of the infant kidney is responsive to exogenous ADH and that its effect is mediated by cAMP. The results of a second series with 52 normally hydrated infants demonstrate that the nonlinear age-related increase of osmolality and urea in urine is accompanied by a similar pattern of cAMP excretion, pointing out that the maturation of the concentrating capacity seems to be related to an increasing responsiveness of the cAMP system to ADH. Furthermore the results raise the possibility that increasing concentrations of urea and solutes in the medulla and papilla of the infant kidney may have--in the presence of very low ADH secretion--an additional stimulating effect on cAMP formation.", "contents": "Urinary cyclic AMP and renal concentrating capacity in infants. In 15 infants between 1 and 31 weeks the effect of antidiuretic hormone (ADH) on the renal concentrating capacity and urinary cyclic AMP (cAMP) was tested. A significant decrease of urine flow and a significant increase of osmolality, urea and cAMP was observed indicating that the distal nephron of the infant kidney is responsive to exogenous ADH and that its effect is mediated by cAMP. The results of a second series with 52 normally hydrated infants demonstrate that the nonlinear age-related increase of osmolality and urea in urine is accompanied by a similar pattern of cAMP excretion, pointing out that the maturation of the concentrating capacity seems to be related to an increasing responsiveness of the cAMP system to ADH. Furthermore the results raise the possibility that increasing concentrations of urea and solutes in the medulla and papilla of the infant kidney may have--in the presence of very low ADH secretion--an additional stimulating effect on cAMP formation."}
{"id": "PMID:188658", "title": "Extracerebrospinal metastases in glioblastoma. Case report and review of the literature.", "content": "A malignant glioblastoma adherent to the dura mater was removed from the parieto-occipital lobe in a 12-year-old boy. The site of the tumor was subsequently irridiated by 4000 rads of Cobalt-60. Five months later the boy was readmitted complaining  of pains in the pelvis an in both thighs. X-ray examination of the pelvis demonstrated multiple metastases. Investigation of bone marrow revealed replacement of normal haematopoiesis by a tumor cell population histologically identical to that of the brain tumor. Reviewing the literature 58 reports on glioblastomas with extracerebrospinal metastases could be found. Metastases were preferably localized in cervical or mediastinal lymph nodes, lungs, bones, liver, dura mater, and operative flap. It is suggested that extracerebrospinal metastases occur most frequently after the tumor has infiltrated the cranium and extracranial soft tissues. In the case reported here it is speculated that the tumor spread to extraneural tissues after invading the dural veins. The possible occurrence of extracerebrospinal metastases in glioblastoma emphasizes the necessity of additional chemotherapy.", "contents": "Extracerebrospinal metastases in glioblastoma. Case report and review of the literature. A malignant glioblastoma adherent to the dura mater was removed from the parieto-occipital lobe in a 12-year-old boy. The site of the tumor was subsequently irridiated by 4000 rads of Cobalt-60. Five months later the boy was readmitted complaining  of pains in the pelvis an in both thighs. X-ray examination of the pelvis demonstrated multiple metastases. Investigation of bone marrow revealed replacement of normal haematopoiesis by a tumor cell population histologically identical to that of the brain tumor. Reviewing the literature 58 reports on glioblastomas with extracerebrospinal metastases could be found. Metastases were preferably localized in cervical or mediastinal lymph nodes, lungs, bones, liver, dura mater, and operative flap. It is suggested that extracerebrospinal metastases occur most frequently after the tumor has infiltrated the cranium and extracranial soft tissues. In the case reported here it is speculated that the tumor spread to extraneural tissues after invading the dural veins. The possible occurrence of extracerebrospinal metastases in glioblastoma emphasizes the necessity of additional chemotherapy."}
{"id": "PMID:188660", "title": "Cyclic 3',5'-adenosine monophosphate and bronchial tone.", "content": "The present studies demonstrate that adenylate cyclase and cyclic 3',5'-adenosine monophosphate (cAMP)-phosphodiesterase activities in dog bronchus are comparable to those found in other smooth muscle preparations. Catecholamines, in the order isoproterenol greater than epinephrine greater than norepinephrine, increase the rate of cAMP formation. This effect can be competitively inhibited by propranolol and potentiated by a cAMP-phosphodiesterase inhibitor. The kinetic study of bronchial cAMP-phosphodiesterase showed two different rates of cAMP hydrolysis, with apparent Km values of 1.4 and 48.0 muM. The high affinity cAMP-phosphodiesterase was inhibited competitively by theophylline and papaverine, the latter being about 20 times more potent than the former. The potency of each compound to inhibit the enzyme and to relax the bronchial strip was comparable. These results, the similar order of potency of the catecholamines to relax the bronchus and to increase the rate of cAMP formation, the competitive inhibition of both effects by propranolol, and the relaxing effect of dibutyryl cAMP on bronchial strip, are compatible with the assumption that the cAMP system is one of the biochemical mechanisms mediating bronchial smooth muscle relaxation.", "contents": "Cyclic 3',5'-adenosine monophosphate and bronchial tone. The present studies demonstrate that adenylate cyclase and cyclic 3',5'-adenosine monophosphate (cAMP)-phosphodiesterase activities in dog bronchus are comparable to those found in other smooth muscle preparations. Catecholamines, in the order isoproterenol greater than epinephrine greater than norepinephrine, increase the rate of cAMP formation. This effect can be competitively inhibited by propranolol and potentiated by a cAMP-phosphodiesterase inhibitor. The kinetic study of bronchial cAMP-phosphodiesterase showed two different rates of cAMP hydrolysis, with apparent Km values of 1.4 and 48.0 muM. The high affinity cAMP-phosphodiesterase was inhibited competitively by theophylline and papaverine, the latter being about 20 times more potent than the former. The potency of each compound to inhibit the enzyme and to relax the bronchial strip was comparable. These results, the similar order of potency of the catecholamines to relax the bronchus and to increase the rate of cAMP formation, the competitive inhibition of both effects by propranolol, and the relaxing effect of dibutyryl cAMP on bronchial strip, are compatible with the assumption that the cAMP system is one of the biochemical mechanisms mediating bronchial smooth muscle relaxation."}
{"id": "PMID:188662", "title": "Strain differences in responsiveness of norepinephrine-sensitive adenosine 3',5'-monophosphate-generating systems in rat brain slices after intraventricular administration of 6-hydroxydopamine.", "content": "The development of hyperresponsiveness in cyclic AMP-generating systems has been investigated in brain slices of Sprague-Dawley and F-344 rats following intraventricular administration of 6-hydroxydopamine. Hyperresponsiveness to adrenergic agonists in cerebral cortical slices of Sprague-Dawley rats pertained during the period 5-25 days after treatment with 6-hydroxydopamine. In contrast, hyperresponsiveness did not develop in cerebral cortical slices of F-344 rats. Reductions in norepinephrine levels of the cerebral cortex and hypothalamus following 6-hydroxydopamine treatment were comparable in the two rat strains. A hyperresponsiveness to norepinephrine and isoproterenol failed to develop in mesencephalic slices of either strain 12-14 days after treatment with 6-hydroxydopamine. The accumulation of cyclic AMP elicited by norepinephrine in cortical slices of F-344 rat is normally about 50% greater than the accumulation elicited in slices from Sprague-Dawley rats. However, after 6-hydroxydopamine treatment, there was no significant difference in the accumulations of cyclic AMP elicited in cortical slices from the two rat strains. These data indicate there may be a limit to the responsiveness of catecholamine-sensitive cyclic AMP generating systems which can develop following alterations in synaptic input.", "contents": "Strain differences in responsiveness of norepinephrine-sensitive adenosine 3',5'-monophosphate-generating systems in rat brain slices after intraventricular administration of 6-hydroxydopamine. The development of hyperresponsiveness in cyclic AMP-generating systems has been investigated in brain slices of Sprague-Dawley and F-344 rats following intraventricular administration of 6-hydroxydopamine. Hyperresponsiveness to adrenergic agonists in cerebral cortical slices of Sprague-Dawley rats pertained during the period 5-25 days after treatment with 6-hydroxydopamine. In contrast, hyperresponsiveness did not develop in cerebral cortical slices of F-344 rats. Reductions in norepinephrine levels of the cerebral cortex and hypothalamus following 6-hydroxydopamine treatment were comparable in the two rat strains. A hyperresponsiveness to norepinephrine and isoproterenol failed to develop in mesencephalic slices of either strain 12-14 days after treatment with 6-hydroxydopamine. The accumulation of cyclic AMP elicited by norepinephrine in cortical slices of F-344 rat is normally about 50% greater than the accumulation elicited in slices from Sprague-Dawley rats. However, after 6-hydroxydopamine treatment, there was no significant difference in the accumulations of cyclic AMP elicited in cortical slices from the two rat strains. These data indicate there may be a limit to the responsiveness of catecholamine-sensitive cyclic AMP generating systems which can develop following alterations in synaptic input."}
{"id": "PMID:188663", "title": "Dopamine-sensitive adenylate cyclase in the rat kidney particulate preparation.", "content": "Dopamine, apomorphine, isoproterenol and norepinephrine all increased the concentration of adenosine 3',5'-monophosphate in the rat kidney particulate preparation, which was composed of tubules, glomeruli and blood vessels. The concentrations of dopamine, apomorphine, isoproterenol and norepinephrine causing a half-maximal increase were 50, 83, 0.1 and 10 muM, respectively. The alpha-blocker, phentolamine, at a concentration as high as 1 mM, did not significantly reduce the effect of these drugs on the adenosine 3',5'-monophosphate concentration. The beta-blocker, propranolol (50 muM), blocked the effect of isoproterenol and norepinephrine, but not that of dopamine. The effect of dopamine was selectively blocked by spiroperidol (50 muM), a dopamine receptor antagonist, whereas the effects of isoproterenol and norepinephrine was not blocked by spiroperidol. These results suggest that in the rat kidney particulate preparation there is a specific dopamine receptor which can lead to the increase in the concentration of adenosine 3',5'-monophosphate.", "contents": "Dopamine-sensitive adenylate cyclase in the rat kidney particulate preparation. Dopamine, apomorphine, isoproterenol and norepinephrine all increased the concentration of adenosine 3',5'-monophosphate in the rat kidney particulate preparation, which was composed of tubules, glomeruli and blood vessels. The concentrations of dopamine, apomorphine, isoproterenol and norepinephrine causing a half-maximal increase were 50, 83, 0.1 and 10 muM, respectively. The alpha-blocker, phentolamine, at a concentration as high as 1 mM, did not significantly reduce the effect of these drugs on the adenosine 3',5'-monophosphate concentration. The beta-blocker, propranolol (50 muM), blocked the effect of isoproterenol and norepinephrine, but not that of dopamine. The effect of dopamine was selectively blocked by spiroperidol (50 muM), a dopamine receptor antagonist, whereas the effects of isoproterenol and norepinephrine was not blocked by spiroperidol. These results suggest that in the rat kidney particulate preparation there is a specific dopamine receptor which can lead to the increase in the concentration of adenosine 3',5'-monophosphate."}
{"id": "PMID:188664", "title": "Effects of adenosine and related compounds on adenylate cyclase and cyclic AMP levels in smooth muscle.", "content": "The hypotheses were tested that the relaxant effect of adenosine and related compounds in the longitudinal muscle of the rabbit small intestine involves interaction with adenylate cyclase and/or the elevation of tissue cAMP levels. Adenylate cyclase was prepared by gentle homogenization of an isolated smooth muscle cell fraction obtained after collagenase digestion of longitudinal muscle strips. A number of analogs and derivatives of adenosine possessing a primary or secondary 6-amino group were found to inhibit the enzyme similarly to adenosine; however, there was no correlation between compounds known to relax the intact tissue and the existence, or the degree of, cyclase inhibition. Isolated muscle strips were exposed to adrenaline, isoprenaline, adenosine or ATP, at doses causing 30-60% relaxation, for 60 sec prior to sampling and analysis of cAMP content. While small increments in cAMP levels were found after administering adrenaline or isoprenaline, no change was found with adenosine in the absence or presence of theophylline of 1-methyl-3-isobutylxanthine. Neither adenylate cyclase inhibition nor changes in cAMP levels appear to be part of the mechanism of the smooth muscle relaxant action of adenosine or ATP.", "contents": "Effects of adenosine and related compounds on adenylate cyclase and cyclic AMP levels in smooth muscle. The hypotheses were tested that the relaxant effect of adenosine and related compounds in the longitudinal muscle of the rabbit small intestine involves interaction with adenylate cyclase and/or the elevation of tissue cAMP levels. Adenylate cyclase was prepared by gentle homogenization of an isolated smooth muscle cell fraction obtained after collagenase digestion of longitudinal muscle strips. A number of analogs and derivatives of adenosine possessing a primary or secondary 6-amino group were found to inhibit the enzyme similarly to adenosine; however, there was no correlation between compounds known to relax the intact tissue and the existence, or the degree of, cyclase inhibition. Isolated muscle strips were exposed to adrenaline, isoprenaline, adenosine or ATP, at doses causing 30-60% relaxation, for 60 sec prior to sampling and analysis of cAMP content. While small increments in cAMP levels were found after administering adrenaline or isoprenaline, no change was found with adenosine in the absence or presence of theophylline of 1-methyl-3-isobutylxanthine. Neither adenylate cyclase inhibition nor changes in cAMP levels appear to be part of the mechanism of the smooth muscle relaxant action of adenosine or ATP."}
{"id": "PMID:188665", "title": "Hypoglycemia induced by alpha-adrenergic stimulation during alkalosis.", "content": "Hypoglycemia developed during respiratory alkalosis in fasted rats. This hypoglycemia was markedly potentiated by the simultaneous injection of inhibitors of hepatic gluconeogenesis or a beta-adrenergic blocking agent; was not influenced by anti-insulin serum; was attenuated by hexamethonium; and was abolished by an alpha-adrenergic blocking agent. The rate of removal of injected glucose by peripheral tissues increased during alkalosis in insulin-deficient rats. The uptake of [14C]-glucose by the adipose tissue in vivo, which is stimulated by a very minute amount of insulin, was also stimulated during alkalosis whether or not the circulating insulin was neutralized with anti-insulin serum. It was concluded that, in alkalotic rats, blood glucose is rapidly utilized by peripheral tissues dependent on alpha-adrenergic stimulation, but without mediation of insulin and that this leads to development of hypoglycemia.", "contents": "Hypoglycemia induced by alpha-adrenergic stimulation during alkalosis. Hypoglycemia developed during respiratory alkalosis in fasted rats. This hypoglycemia was markedly potentiated by the simultaneous injection of inhibitors of hepatic gluconeogenesis or a beta-adrenergic blocking agent; was not influenced by anti-insulin serum; was attenuated by hexamethonium; and was abolished by an alpha-adrenergic blocking agent. The rate of removal of injected glucose by peripheral tissues increased during alkalosis in insulin-deficient rats. The uptake of [14C]-glucose by the adipose tissue in vivo, which is stimulated by a very minute amount of insulin, was also stimulated during alkalosis whether or not the circulating insulin was neutralized with anti-insulin serum. It was concluded that, in alkalotic rats, blood glucose is rapidly utilized by peripheral tissues dependent on alpha-adrenergic stimulation, but without mediation of insulin and that this leads to development of hypoglycemia."}
{"id": "PMID:188673", "title": "Erythroid precursor fusion induced by Sendai virus.", "content": "The ultrastructural events of the interaction of Sendai virus (SV) with fetal mouse erythroid precursors, and SV-induced fusion of erythroid precursors at different maturation stages are described. SV was shown to affect the erythroid nuclei causing interruption of the nuclear membrane, enlargement of the nucleolus and nuclear fusion. SV induced fusion also between dividing and non-dividing cells.", "contents": "Erythroid precursor fusion induced by Sendai virus. The ultrastructural events of the interaction of Sendai virus (SV) with fetal mouse erythroid precursors, and SV-induced fusion of erythroid precursors at different maturation stages are described. SV was shown to affect the erythroid nuclei causing interruption of the nuclear membrane, enlargement of the nucleolus and nuclear fusion. SV induced fusion also between dividing and non-dividing cells."}
{"id": "PMID:188674", "title": "Integration in descending motor pathways controlling the forelimb in the cat. 2. Convergence on neurones mediating disynaptic cortico-motoneuronal excitation.", "content": "With intracellular recording from forelimb motoneurones the spatial facilitation technique has been used to investigate interaction between descending pathways and forelimb afferents. As previously shown for the hindlimb, pyramidal volleys effectively facilitate interneuronal transmission in reflex pathways from different primary afferents. Evidence is presented suggesting disynaptic excitation from corticospinal fibres of interneurones in the reciprocal Ia inhibitory pathway. Interneurones of other reflex pathways from group I muscle afferents recieve monosynaptic pyramidal excitation. During pyramidal facilitation volleys in cutaneous afferents may evoke PSPs in motoneurones after a central delay of 1.3 ms suggesting that the minimal linkage is disynaptic. Information regarding convergence on the neurones intercalated in the disynaptic cortico-motoneuronal pathway was obtained by investigating the effect from primary afferents and from other descending pathways on the disynaptic pyramidal EPSPs. Volleys in cutaneous and group I muscle affferents facilitate transmission in the disynaptic cortico-motoneuronal transmission with a time course showing oligosynaptic (probably monosynaptic) action the intercalated neurone. Rubrospinal volleys likewise effectively facilitate disynaptic cortico-motoneuronal pathway with a time course showing oligosynaptic (probably monosynaptic) action on the intercalated neurone. Rubrospinal volleys likewise effectively facilitate disynaptic cortico-motoneuronal transmission with a time course showing monosynaptic action on the intercalated neurone. Spatial facilitation experiments involving three tests revealed that those intercalated neurones which receive convergent monosynaptic excitation from corticospinal and rubrospinal fibres are excited also from cutaneous forelimb afferents. Disynaptic cortico-motoneuronal transmission was also monosynaptically facilitated by stimuli in the dorsal mesencephalic tegmentum probably activating tectospinal fibres. Disynaptic, presumed tectospinal EPSPs were facilitated from cutaneous forelimb afferents. The convergence onto the neurones intercalated in the disynaptic excitatory cortico-motoneuronal pathway suggests that these neurones integrate the activity in different descending pathways and primary forelimb afferents.", "contents": "Integration in descending motor pathways controlling the forelimb in the cat. 2. Convergence on neurones mediating disynaptic cortico-motoneuronal excitation. With intracellular recording from forelimb motoneurones the spatial facilitation technique has been used to investigate interaction between descending pathways and forelimb afferents. As previously shown for the hindlimb, pyramidal volleys effectively facilitate interneuronal transmission in reflex pathways from different primary afferents. Evidence is presented suggesting disynaptic excitation from corticospinal fibres of interneurones in the reciprocal Ia inhibitory pathway. Interneurones of other reflex pathways from group I muscle afferents recieve monosynaptic pyramidal excitation. During pyramidal facilitation volleys in cutaneous afferents may evoke PSPs in motoneurones after a central delay of 1.3 ms suggesting that the minimal linkage is disynaptic. Information regarding convergence on the neurones intercalated in the disynaptic cortico-motoneuronal pathway was obtained by investigating the effect from primary afferents and from other descending pathways on the disynaptic pyramidal EPSPs. Volleys in cutaneous and group I muscle affferents facilitate transmission in the disynaptic cortico-motoneuronal transmission with a time course showing oligosynaptic (probably monosynaptic) action the intercalated neurone. Rubrospinal volleys likewise effectively facilitate disynaptic cortico-motoneuronal pathway with a time course showing oligosynaptic (probably monosynaptic) action on the intercalated neurone. Rubrospinal volleys likewise effectively facilitate disynaptic cortico-motoneuronal transmission with a time course showing monosynaptic action on the intercalated neurone. Spatial facilitation experiments involving three tests revealed that those intercalated neurones which receive convergent monosynaptic excitation from corticospinal and rubrospinal fibres are excited also from cutaneous forelimb afferents. Disynaptic cortico-motoneuronal transmission was also monosynaptically facilitated by stimuli in the dorsal mesencephalic tegmentum probably activating tectospinal fibres. Disynaptic, presumed tectospinal EPSPs were facilitated from cutaneous forelimb afferents. The convergence onto the neurones intercalated in the disynaptic excitatory cortico-motoneuronal pathway suggests that these neurones integrate the activity in different descending pathways and primary forelimb afferents."}
{"id": "PMID:188679", "title": "Timing of mitosis in Physarum polycephalum: effects of agents affecting cyclic AMP concentrations.", "content": "Cultures of Physarum polycephalum incubated with caffeine or theophylline for over 100 min prior to mitosis exhibited mitotic delay proportional to the time of treatment before 100 min. Starved cultures exhibited mitotic delay at times of starvation longer than 180 min and slight stimulation from 100-180 min. Dibutyryl cAMP appeared to accelerate reconstruction of the nucleus following mitosis.", "contents": "Timing of mitosis in Physarum polycephalum: effects of agents affecting cyclic AMP concentrations. Cultures of Physarum polycephalum incubated with caffeine or theophylline for over 100 min prior to mitosis exhibited mitotic delay proportional to the time of treatment before 100 min. Starved cultures exhibited mitotic delay at times of starvation longer than 180 min and slight stimulation from 100-180 min. Dibutyryl cAMP appeared to accelerate reconstruction of the nucleus following mitosis."}
{"id": "PMID:188680", "title": "Inhibition in the rat of gastric acid secretion and cyclic AMP analogs accumulation in vitro by somatostatin.", "content": "Various somatostatin (S) analogs exhibited similar degree and similar, or shorter, duration of inhibition of basal gastric acid secretion as S in the unanesthetized rat and similar, or less, inhibition of the cyclic AMP accumulation induced by prostaglandin E2 in the rat anterior pituitary in vitro. With the analogs examined, the gastrointestinal and pituitary receptors appear to exhibit generally similar recognition specificity with the differences within the gastro-intestinal activities reflecting duration of availability rather than receptor affinity.", "contents": "Inhibition in the rat of gastric acid secretion and cyclic AMP analogs accumulation in vitro by somatostatin. Various somatostatin (S) analogs exhibited similar degree and similar, or shorter, duration of inhibition of basal gastric acid secretion as S in the unanesthetized rat and similar, or less, inhibition of the cyclic AMP accumulation induced by prostaglandin E2 in the rat anterior pituitary in vitro. With the analogs examined, the gastrointestinal and pituitary receptors appear to exhibit generally similar recognition specificity with the differences within the gastro-intestinal activities reflecting duration of availability rather than receptor affinity."}
{"id": "PMID:188681", "title": "Morphometric study of the aortic body type I cell.", "content": "The subclavian glomus (aortic body) of New Zealand white rabbits was examined ultrastructurally using stereological morphometric analysis. The Type I cells of the glomus possess numerous electron-opaque vesicles which occupy approximately 12% of the cytoplasmic volume of the cells. The amine-containing vesicles comprise a heterogeneous population of vesicles with a mean caliper diameter of 113.5 nm. Differences in vesicle diameters may indicate the storage of different biogenic amines, different secretion or maturation states between glomera and/or additional physiological functions for the glomera.", "contents": "Morphometric study of the aortic body type I cell. The subclavian glomus (aortic body) of New Zealand white rabbits was examined ultrastructurally using stereological morphometric analysis. The Type I cells of the glomus possess numerous electron-opaque vesicles which occupy approximately 12% of the cytoplasmic volume of the cells. The amine-containing vesicles comprise a heterogeneous population of vesicles with a mean caliper diameter of 113.5 nm. Differences in vesicle diameters may indicate the storage of different biogenic amines, different secretion or maturation states between glomera and/or additional physiological functions for the glomera."}
{"id": "PMID:188685", "title": "The effect of distamycin A on some biochemical functions of tissue cultures infected with Herpes simplex virus.", "content": "The antibiotic distamycin A displays no inhibition of protein synthesis in HeLa cell cultures. In HSV infected HeLa cell monolayers the drug exerts a partial inhibition of virus induced thymidine kinase synthesis but is devoid of inhibitory effect on the increase of activity of DNA polymerase and on total DNA synthesis. The antiviral activity of distamycin A is based on a mechanism which appears to be different from that displayed by other drugs such as actinomycin and IUD.", "contents": "The effect of distamycin A on some biochemical functions of tissue cultures infected with Herpes simplex virus. The antibiotic distamycin A displays no inhibition of protein synthesis in HeLa cell cultures. In HSV infected HeLa cell monolayers the drug exerts a partial inhibition of virus induced thymidine kinase synthesis but is devoid of inhibitory effect on the increase of activity of DNA polymerase and on total DNA synthesis. The antiviral activity of distamycin A is based on a mechanism which appears to be different from that displayed by other drugs such as actinomycin and IUD."}
{"id": "PMID:188686", "title": "Micropuncture studies of the motility of rete testis and epididymal spermatozoa.", "content": "The effect of cyclic adenosine 3':5'-monophosphate (cAMP) and caffeine on the motility of spermatozoa obtained in vivo by micropuncture from the rat rete testis, caput epidiymidis, and cauda epididymidis was studied. Spermatozoa from all sites were immobile in their native fluid. Rete testis spermatozoa were not motile under any experimental conditions. After dilution in salt solution, some caput sperm exhibited circular motion, whereas most cauda sperm swam progressively. Dextrose enhanced the motility of sperm from both epidiymal sites. Caffeine further increased the motility of epididymal sperm. Dibutyryl cAMP and cAMP stimulated caput spermatozoa but had no effect on cauda spermatozoa.", "contents": "Micropuncture studies of the motility of rete testis and epididymal spermatozoa. The effect of cyclic adenosine 3':5'-monophosphate (cAMP) and caffeine on the motility of spermatozoa obtained in vivo by micropuncture from the rat rete testis, caput epidiymidis, and cauda epididymidis was studied. Spermatozoa from all sites were immobile in their native fluid. Rete testis spermatozoa were not motile under any experimental conditions. After dilution in salt solution, some caput sperm exhibited circular motion, whereas most cauda sperm swam progressively. Dextrose enhanced the motility of sperm from both epidiymal sites. Caffeine further increased the motility of epididymal sperm. Dibutyryl cAMP and cAMP stimulated caput spermatozoa but had no effect on cauda spermatozoa."}
{"id": "PMID:188689", "title": "[Electrical activity of layers of isolated cortex during drowsiness and different sleep stages].", "content": "In cats with isolated cerebral cortex, with the aid of electordes indwelled into different cortical layers, first electrographic changes during onset of sleep were shown to occur, as with intact cortex, in the lower layers of the isolated cortex. 3-4 months after the cortex isolation, changes of electrical activity during sleep occured simultaneously in the cortex of both hemispheres. Awakening produced desynchronization of electrical activity in all cortical layers of both hemispheres. Origin of primary electrical activity changes in the lower cortical layers, is discussed.", "contents": "[Electrical activity of layers of isolated cortex during drowsiness and different sleep stages]. In cats with isolated cerebral cortex, with the aid of electordes indwelled into different cortical layers, first electrographic changes during onset of sleep were shown to occur, as with intact cortex, in the lower layers of the isolated cortex. 3-4 months after the cortex isolation, changes of electrical activity during sleep occured simultaneously in the cortex of both hemispheres. Awakening produced desynchronization of electrical activity in all cortical layers of both hemispheres. Origin of primary electrical activity changes in the lower cortical layers, is discussed."}
{"id": "PMID:188692", "title": "[Myocardial cell adenyl cyclase activity and the effect of thyrocalcitonin].", "content": "The thyrocalcitonin (TCT) effect under influence of some factors affecting the activity of membrane adenylcyclase (AC) of the ventricle myocardial cells in cold-blooded animals, was studied. The TCT positive inotropic effect is intensified by decrease in the potassium concentration in the medium, by blockade of alpha-adrenoreceptors with phentolamine, and inhibited by increase in the potassium concentration and blockade of beta-adrenoreceptors. The TCT action is preserved in presence of adrenaline.", "contents": "[Myocardial cell adenyl cyclase activity and the effect of thyrocalcitonin]. The thyrocalcitonin (TCT) effect under influence of some factors affecting the activity of membrane adenylcyclase (AC) of the ventricle myocardial cells in cold-blooded animals, was studied. The TCT positive inotropic effect is intensified by decrease in the potassium concentration in the medium, by blockade of alpha-adrenoreceptors with phentolamine, and inhibited by increase in the potassium concentration and blockade of beta-adrenoreceptors. The TCT action is preserved in presence of adrenaline."}
{"id": "PMID:188693", "title": "[Participation of histamine in activating the hypothalamo-hypophyseo-adrenal system during stress].", "content": "In 289 male rats, accumulation of histamine in diencephalon, augmentation of activity in the hypothalamus, and increase of the ACTH content in the hypophysis and 11-OCS in adrenal and plasma were revealed under a functional stress for the hypothalamo-hypophyseal-adrenal system (HHAS). Further accumulation of histamine was associated with increased secretion of CRF, ACTH, and 11-OCS. Blocking of histamine by diphenylhydramine hydrochloride (10.0 mg/kg i. p. -- 30 min before the experiment) depressed the rate and intensity of the initial reaction of HHAS activation.", "contents": "[Participation of histamine in activating the hypothalamo-hypophyseo-adrenal system during stress]. In 289 male rats, accumulation of histamine in diencephalon, augmentation of activity in the hypothalamus, and increase of the ACTH content in the hypophysis and 11-OCS in adrenal and plasma were revealed under a functional stress for the hypothalamo-hypophyseal-adrenal system (HHAS). Further accumulation of histamine was associated with increased secretion of CRF, ACTH, and 11-OCS. Blocking of histamine by diphenylhydramine hydrochloride (10.0 mg/kg i. p. -- 30 min before the experiment) depressed the rate and intensity of the initial reaction of HHAS activation."}
{"id": "PMID:188694", "title": "[Effect of a periodic growth-retarding diet on changes with age in the hypothalamo-hypophyseo-adrenal system].", "content": "Two pacemakers localized in sinoatrial and atrioventricular valves were revealed in the tench heart. In their absence, the ventricular and sometimes the atrial myocardium are capable of initialting the automaticity. Pacemaker's cells of the sinoatrial valve are surrounded by specific area similar to sinoauricular ring in amphibia or sino-caval region in mammals. Characteristics of the action potential in different parts of the tench heart are presented.", "contents": "[Effect of a periodic growth-retarding diet on changes with age in the hypothalamo-hypophyseo-adrenal system]. Two pacemakers localized in sinoatrial and atrioventricular valves were revealed in the tench heart. In their absence, the ventricular and sometimes the atrial myocardium are capable of initialting the automaticity. Pacemaker's cells of the sinoatrial valve are surrounded by specific area similar to sinoauricular ring in amphibia or sino-caval region in mammals. Characteristics of the action potential in different parts of the tench heart are presented."}
{"id": "PMID:188697", "title": "Somatostatin-induced inhibition of insulin secretion by isolated pancreatic rat islets prepared by micro-dissection or collagenase digestion.", "content": "The effect of somatostatin on insulin secretion in response to a variety of stimuli was investigated in micro-dissected as well as collagenase isolated pancreatic rat islets. Somatostatin inhibited insulin secretion in both islet preparations in the presence of different initiators, but failed to affect the hormone output induced by theophylline, 1-methyl-3-isobutylxanthin (IBMX) or p-chloromercuriphenylsulfonic acid (CMBS). The inhibitory action was associated with decreased glucose metabolism by islets (measured as conversion of U-14C-glucose to 14CO2).", "contents": "Somatostatin-induced inhibition of insulin secretion by isolated pancreatic rat islets prepared by micro-dissection or collagenase digestion. The effect of somatostatin on insulin secretion in response to a variety of stimuli was investigated in micro-dissected as well as collagenase isolated pancreatic rat islets. Somatostatin inhibited insulin secretion in both islet preparations in the presence of different initiators, but failed to affect the hormone output induced by theophylline, 1-methyl-3-isobutylxanthin (IBMX) or p-chloromercuriphenylsulfonic acid (CMBS). The inhibitory action was associated with decreased glucose metabolism by islets (measured as conversion of U-14C-glucose to 14CO2)."}
{"id": "PMID:188698", "title": "Hypolipidemic effects of metformin in hyperprebetalipoproteinemia.", "content": "Metformin's hypolipidemic effects (2.55 g/day for 3 months) have been studied in 19 subjects with Fredrickson's Type IV hyperprebetalipoproteinemia. The majority of patients were above ideal body weight (relative body weight = 118 +/- 2.7 %). Eleven of the subjects presented chemical diabetes, 5 fasting hyperglycemia, and 3 normal glucose tolerance. After treatment with metformin, body weight showed a slight, but significant reduction (--2.4 +/- 0.3 kg). Glucose tolerence was not substantially altered while basal glucose was significantly reduced in the 5 subjects with fasting hyperglycemia. Basal plasma insulin was significantly reduced in all the patients following metformin treatment. Insulin response to OGTT was slightly reduced in the subjects with fasting hyperglycemia. Independent of the patients' glucose tolerance, metformin treatment induced a marked decrease in plasma triglycerides (-- 40 %) and a reduction in plasma cholesterol (-- 12 %). No correlation was found between triglyceride and cholesterol reduction and body weight, glucose, and plasma insulin variations. Like phenformin, metformin acts not only on glucose metabolism and insulin secretion but on lipid metabolism as well.", "contents": "Hypolipidemic effects of metformin in hyperprebetalipoproteinemia. Metformin's hypolipidemic effects (2.55 g/day for 3 months) have been studied in 19 subjects with Fredrickson's Type IV hyperprebetalipoproteinemia. The majority of patients were above ideal body weight (relative body weight = 118 +/- 2.7 %). Eleven of the subjects presented chemical diabetes, 5 fasting hyperglycemia, and 3 normal glucose tolerance. After treatment with metformin, body weight showed a slight, but significant reduction (--2.4 +/- 0.3 kg). Glucose tolerence was not substantially altered while basal glucose was significantly reduced in the 5 subjects with fasting hyperglycemia. Basal plasma insulin was significantly reduced in all the patients following metformin treatment. Insulin response to OGTT was slightly reduced in the subjects with fasting hyperglycemia. Independent of the patients' glucose tolerance, metformin treatment induced a marked decrease in plasma triglycerides (-- 40 %) and a reduction in plasma cholesterol (-- 12 %). No correlation was found between triglyceride and cholesterol reduction and body weight, glucose, and plasma insulin variations. Like phenformin, metformin acts not only on glucose metabolism and insulin secretion but on lipid metabolism as well."}
{"id": "PMID:188702", "title": "The interaction of hCG with rat adipose tissue: apparent lack of hCG--LH receptors.", "content": "The interaction of human chorionic gonadotropin (hCG) with rat adipose tissue was investigated by both metabolic and binding studies. Highly purified preparations of hCG did not affect the adenylate cyclase activity nor the lipolysis of rat adipocytes in the presence or in the absence of GTP. However, it was demonstrated that (a) the hCGs used were biologically active since they stimulated cAMP and testosterone production by rat Leydig cells, and (b) there are receptor sites on the rat ovary that bind [125I]hCG and recognize rat luteinizing hormone (LH). The lack of response cannot then be attributed to a loss of activity of the hormone preparation tested nor to a failure of the rat tissues to recognize an hormone of human origin, but rather to an absence of hCG--LH receptors on the fat cell membrane surface. It is suggested that results previously reported in other laboratories could be explained by the presence of contaminating amounts of lipolytic hormones in their preparations.", "contents": "The interaction of hCG with rat adipose tissue: apparent lack of hCG--LH receptors. The interaction of human chorionic gonadotropin (hCG) with rat adipose tissue was investigated by both metabolic and binding studies. Highly purified preparations of hCG did not affect the adenylate cyclase activity nor the lipolysis of rat adipocytes in the presence or in the absence of GTP. However, it was demonstrated that (a) the hCGs used were biologically active since they stimulated cAMP and testosterone production by rat Leydig cells, and (b) there are receptor sites on the rat ovary that bind [125I]hCG and recognize rat luteinizing hormone (LH). The lack of response cannot then be attributed to a loss of activity of the hormone preparation tested nor to a failure of the rat tissues to recognize an hormone of human origin, but rather to an absence of hCG--LH receptors on the fat cell membrane surface. It is suggested that results previously reported in other laboratories could be explained by the presence of contaminating amounts of lipolytic hormones in their preparations."}
{"id": "PMID:188703", "title": "Adenosine 3',5'-monophosphate-dependent protein kinase from normal human adrenal.", "content": "The protein kinase of normal human adrenal cytosol has been resolved by DEAE-cellulose chromatography into two major components, the protein kinases I and II, which are both adenosine 3',5'-monophosphate (cAMP) dependent. Both enzymes have similar substrate specificities, cAMP-dependency, and sensitivity to the stimulation by this nucleotide, but differ in their states of activation after preincubation with histone. The DEAE--cellulose charomatography of dissociated cytosol protein kinase reveals only one peak of kinase activity and two peaks of cAMP binding activity (A and B). Both binding proteins are able to inhibit the kinase activity of the catalytic subunit. Recombination experiments suggest that the regulatory subunit A originated from protein kinase I and subunit B from protein kinase II. The phosphorylation of histone by adrenal protein kinases is inhibited by a heat-stable protein inhibitor isolated from human fetal brain and human adult adrenal.", "contents": "Adenosine 3',5'-monophosphate-dependent protein kinase from normal human adrenal. The protein kinase of normal human adrenal cytosol has been resolved by DEAE-cellulose chromatography into two major components, the protein kinases I and II, which are both adenosine 3',5'-monophosphate (cAMP) dependent. Both enzymes have similar substrate specificities, cAMP-dependency, and sensitivity to the stimulation by this nucleotide, but differ in their states of activation after preincubation with histone. The DEAE--cellulose charomatography of dissociated cytosol protein kinase reveals only one peak of kinase activity and two peaks of cAMP binding activity (A and B). Both binding proteins are able to inhibit the kinase activity of the catalytic subunit. Recombination experiments suggest that the regulatory subunit A originated from protein kinase I and subunit B from protein kinase II. The phosphorylation of histone by adrenal protein kinases is inhibited by a heat-stable protein inhibitor isolated from human fetal brain and human adult adrenal."}
{"id": "PMID:188704", "title": "Apparent positive cooperativity of ACTH action on adrenocortical cells: the effect of hormone degradation.", "content": "The ability of adrenocortical cells to degrade ACTH1--39 and [125I]ACTH has been assessed under various conditions. Under conditions leading to increased hormone degradation there was an elevation of both the ED50 and the value of the Hill coefficient derived from concentration-effect curves for ACTH-stimulated steroidogenesis. Such degradative mechanisms offer a simple explanation for tha apparent positive cooperativity proposed by others for ACTH-receptor-adenylate cyclase interactions.", "contents": "Apparent positive cooperativity of ACTH action on adrenocortical cells: the effect of hormone degradation. The ability of adrenocortical cells to degrade ACTH1--39 and [125I]ACTH has been assessed under various conditions. Under conditions leading to increased hormone degradation there was an elevation of both the ED50 and the value of the Hill coefficient derived from concentration-effect curves for ACTH-stimulated steroidogenesis. Such degradative mechanisms offer a simple explanation for tha apparent positive cooperativity proposed by others for ACTH-receptor-adenylate cyclase interactions."}
{"id": "PMID:188707", "title": "Insulin receptor sites as membrane markers during embryonic development. I. Data obtained with unfertilized and fertilized sea urchin eggs.", "content": "Binding of insulin to sea urchin egg plasma membrane has been studied by biochemical and immunocytochemical methods. Unfertilized and fertilized eggs as well as embryos during the first cell division have been used. 1. Competition experiments between 125I-insulin (1 nM) and an excess of native insulin (30 muM) indicate a specific hormone fixation to membrane crude extracts from unfertilized and fertilized eggs. The magnitude of \"specific binding\" is comparable to values recorded for mammalian cells. 2. Inhibition of insulin fixation by concanavalin A (100 mug/ml) suggests the glycoprotein composition of plasma membrane receptors. 3. An 30-min incubation of unfertilized and fertilized eggs in the presence of insulin leads to a significant increase in cyclic AMP content. 4. An immunocytochemical method demonstrates that insulin is selectively and specifically bound to the plasma membrane of eggs incubated in the presence of insulin before fixation. It can be concluded that insulin receptor sites are components of sea urchin eggs plasma membrane. Insulin binding which leads to cyclic AMP accumulation is not deeply modified by fertilization and does not include visible morphological changes in the eggs.", "contents": "Insulin receptor sites as membrane markers during embryonic development. I. Data obtained with unfertilized and fertilized sea urchin eggs. Binding of insulin to sea urchin egg plasma membrane has been studied by biochemical and immunocytochemical methods. Unfertilized and fertilized eggs as well as embryos during the first cell division have been used. 1. Competition experiments between 125I-insulin (1 nM) and an excess of native insulin (30 muM) indicate a specific hormone fixation to membrane crude extracts from unfertilized and fertilized eggs. The magnitude of \"specific binding\" is comparable to values recorded for mammalian cells. 2. Inhibition of insulin fixation by concanavalin A (100 mug/ml) suggests the glycoprotein composition of plasma membrane receptors. 3. An 30-min incubation of unfertilized and fertilized eggs in the presence of insulin leads to a significant increase in cyclic AMP content. 4. An immunocytochemical method demonstrates that insulin is selectively and specifically bound to the plasma membrane of eggs incubated in the presence of insulin before fixation. It can be concluded that insulin receptor sites are components of sea urchin eggs plasma membrane. Insulin binding which leads to cyclic AMP accumulation is not deeply modified by fertilization and does not include visible morphological changes in the eggs."}
{"id": "PMID:188708", "title": "Squamous cell differentiation in a clonal teratocarcinoma cell line.", "content": "Several clonal teratocarcinoma cell lines restricted to squamous cell differentiation have been established from a subculture of totipotential murine teratocarcinoma stem cells. These lines contain a continuum of cell types from less differentiated precursor cells to differentiated squamous cells. In contrast to their highly malignant progenitors, these cells are nontumorigenic. Chromosomally, the cells are near-tetraploid, and their DNA distributions are tetraploid. These cells lines may prove useful in the study of normal squamous cell differentiation and also will be important in studies concerning the conversion of malignant cells to non-malignant progeny.", "contents": "Squamous cell differentiation in a clonal teratocarcinoma cell line. Several clonal teratocarcinoma cell lines restricted to squamous cell differentiation have been established from a subculture of totipotential murine teratocarcinoma stem cells. These lines contain a continuum of cell types from less differentiated precursor cells to differentiated squamous cells. In contrast to their highly malignant progenitors, these cells are nontumorigenic. Chromosomally, the cells are near-tetraploid, and their DNA distributions are tetraploid. These cells lines may prove useful in the study of normal squamous cell differentiation and also will be important in studies concerning the conversion of malignant cells to non-malignant progeny."}
{"id": "PMID:188710", "title": "Abnormal plasma lipoproteins and lecithin-cholesterol acyltransferase deficiency in alcoholic liver disease.", "content": "Serial studies of plasma lipids and lipoproteins were performed in 4 patients with acute alcoholic liver disease characterized by a massive fatty liver and laboratory evidence of intrahepatic cholestasis. There were striking alterations in the plasma lipoprotein electrophoretic patterns characterized by the absence of alpha- and pre-beta-lipoprotein bands and the presence of a single band of abnormal mobility. These changes were associated with an extreme decrease in plasma lecithin-cholesterol acyltransferase activity, resulting in greatly reduced levels of plasma cholesteryl esters and increased levels of unesterified cholesterol. In 2 patients hypertriglyceridemia and hypercholesterolemia were present, the latter because of an increase in unesterified cholesterol. Lipoproteins were isolated from the plasma by sequential ultracentrifugation at the densities used for separation of normal very low density, low density, and high density lipoproteins; however, the patients' lipoproteins were different from normal in lipid composition and ultrastructure. All of the lipoprotein fractions were decreased in cholesteryl esters and the major lipoprotein was a triglyceride-rich low density lipoprotein. Electron microscopic studies of the low and high density lipoprotein fractions revealed the presence of bilamellar vesicles and stacked discs. All of the changes in lipoprotein composition and ultrastructure gradually returned to normal with clinical improvement. These observations indicate that alcoholic liver injury is associated with profound alterations in lipoprotein composition and metabolism which may be related in part to lecithin-cholesterol acyltransferase deficiency.", "contents": "Abnormal plasma lipoproteins and lecithin-cholesterol acyltransferase deficiency in alcoholic liver disease. Serial studies of plasma lipids and lipoproteins were performed in 4 patients with acute alcoholic liver disease characterized by a massive fatty liver and laboratory evidence of intrahepatic cholestasis. There were striking alterations in the plasma lipoprotein electrophoretic patterns characterized by the absence of alpha- and pre-beta-lipoprotein bands and the presence of a single band of abnormal mobility. These changes were associated with an extreme decrease in plasma lecithin-cholesterol acyltransferase activity, resulting in greatly reduced levels of plasma cholesteryl esters and increased levels of unesterified cholesterol. In 2 patients hypertriglyceridemia and hypercholesterolemia were present, the latter because of an increase in unesterified cholesterol. Lipoproteins were isolated from the plasma by sequential ultracentrifugation at the densities used for separation of normal very low density, low density, and high density lipoproteins; however, the patients' lipoproteins were different from normal in lipid composition and ultrastructure. All of the lipoprotein fractions were decreased in cholesteryl esters and the major lipoprotein was a triglyceride-rich low density lipoprotein. Electron microscopic studies of the low and high density lipoprotein fractions revealed the presence of bilamellar vesicles and stacked discs. All of the changes in lipoprotein composition and ultrastructure gradually returned to normal with clinical improvement. These observations indicate that alcoholic liver injury is associated with profound alterations in lipoprotein composition and metabolism which may be related in part to lecithin-cholesterol acyltransferase deficiency."}
{"id": "PMID:188711", "title": "Cytomegalovirus-associated gastric ulcer.", "content": "A patients with a cytomegalovirus (CMV) post-transfusion syndrome developed upper gastrointestinal tract bleeding; subsequently, a gastric ulcer was found. CMV was searched for in the gastroscopic biopsy material because the gastric ulcer had occurred in a setting of CMV mononucleosis. CMV cells were found in gastroscopic biopsy sections and CMV was also cultured from biopsy material. This study illustrates the feasibility of antemortem diagnosis of CMV-associated disease of the upper gastrointestinal tract.", "contents": "Cytomegalovirus-associated gastric ulcer. A patients with a cytomegalovirus (CMV) post-transfusion syndrome developed upper gastrointestinal tract bleeding; subsequently, a gastric ulcer was found. CMV was searched for in the gastroscopic biopsy material because the gastric ulcer had occurred in a setting of CMV mononucleosis. CMV cells were found in gastroscopic biopsy sections and CMV was also cultured from biopsy material. This study illustrates the feasibility of antemortem diagnosis of CMV-associated disease of the upper gastrointestinal tract."}
{"id": "PMID:188713", "title": "Cytological studies of the effect of hepatocarcinogens on liver cells of rats.", "content": "Morphological and cytological changes of liver cells were studied under sequential feeding of p-dimethylaminoazobenzend (DAB) and CCl4 injection. It was found that in hepatic cells of experimental animals definite macroscopical alterations occurred manifested in a change in the colour and the external texture of the liver, the appearance of nodules of different sizes, segmentation, and the abdominal cavity became filled with ascitic fluid, associated with spleenomegaly. The histopathological changes include a disturbance of the normal regularity of hepatic cells, nuclear atypia, hyperchromatism, vaculation of the cytoplasm and decreased mitochondrial and Golgi elements.", "contents": "Cytological studies of the effect of hepatocarcinogens on liver cells of rats. Morphological and cytological changes of liver cells were studied under sequential feeding of p-dimethylaminoazobenzend (DAB) and CCl4 injection. It was found that in hepatic cells of experimental animals definite macroscopical alterations occurred manifested in a change in the colour and the external texture of the liver, the appearance of nodules of different sizes, segmentation, and the abdominal cavity became filled with ascitic fluid, associated with spleenomegaly. The histopathological changes include a disturbance of the normal regularity of hepatic cells, nuclear atypia, hyperchromatism, vaculation of the cytoplasm and decreased mitochondrial and Golgi elements."}
{"id": "PMID:188714", "title": "[The subcapsular blastema of the adrenal cortex of the swine after continuous long-term infusion of exogenous ACTH].", "content": "After long time application of homologous ACTH the morphokinesis of the adrenal cortex of the pig was investigated experimentally. Following results were obtained: 1. In view of the controls the absolute and relative weight of the adrenals is raised considerably. 2. The progressive transformation is followed by the disappearance of the zonal structure of the adrenal cortex, and the parenchyma get the picture of fasciculata cells generally. 3. Nearly exclusive the zona fasciculata consists of great, pale activated spongiocytes with 2 nucleoli frequently. Topochemically glycogen and the lipids are inconstant, however the histochemical activity of succinodehydrogenase, lactate dehydrogenase, acid and alkaline phosphatase are considerable raised in regard of the controls. 4. The zona fasciculata contains degenerated cells isolated only. Signs of extensive regressive changes are not present. 5. The zona glomerulosa is dissolving or eliminating respectively. The consequences for the synthesis of the adrenal steroid hormones are discussed. 6. A large, spongy subcapsular blastema with several cell layers and a rich capillary network develop between the fibrous capsula of the adrenal and the zona fasiculata. The fasciculata cells are the direct continuation of the subcapsular blastema. The blastema contains neither glycogen nor lipids and histochemical activities of the enzymes are absent, too. The significance of the subcapsular blastema for the morphological and functional adaptation of the adrenal cortex in stress are discussed. Under the conditions of the closed hypothalamo-hypophyseal-adrenal control system the new origin of cells (hyperplasia) is not significant for the morphokinetic adaptive reactions of the adrenal cortex. Rather the subcapsular blastema represents a reserve area which after the destruction of the endocrine parenchyma through specific pathogens the organism enabled to the regeneration of the adrenal cortex.", "contents": "[The subcapsular blastema of the adrenal cortex of the swine after continuous long-term infusion of exogenous ACTH]. After long time application of homologous ACTH the morphokinesis of the adrenal cortex of the pig was investigated experimentally. Following results were obtained: 1. In view of the controls the absolute and relative weight of the adrenals is raised considerably. 2. The progressive transformation is followed by the disappearance of the zonal structure of the adrenal cortex, and the parenchyma get the picture of fasciculata cells generally. 3. Nearly exclusive the zona fasciculata consists of great, pale activated spongiocytes with 2 nucleoli frequently. Topochemically glycogen and the lipids are inconstant, however the histochemical activity of succinodehydrogenase, lactate dehydrogenase, acid and alkaline phosphatase are considerable raised in regard of the controls. 4. The zona fasciculata contains degenerated cells isolated only. Signs of extensive regressive changes are not present. 5. The zona glomerulosa is dissolving or eliminating respectively. The consequences for the synthesis of the adrenal steroid hormones are discussed. 6. A large, spongy subcapsular blastema with several cell layers and a rich capillary network develop between the fibrous capsula of the adrenal and the zona fasiculata. The fasciculata cells are the direct continuation of the subcapsular blastema. The blastema contains neither glycogen nor lipids and histochemical activities of the enzymes are absent, too. The significance of the subcapsular blastema for the morphological and functional adaptation of the adrenal cortex in stress are discussed. Under the conditions of the closed hypothalamo-hypophyseal-adrenal control system the new origin of cells (hyperplasia) is not significant for the morphokinetic adaptive reactions of the adrenal cortex. Rather the subcapsular blastema represents a reserve area which after the destruction of the endocrine parenchyma through specific pathogens the organism enabled to the regeneration of the adrenal cortex."}
{"id": "PMID:188716", "title": "[Efficacy of angiography for the diagnosis of trophoblastic tumors (author's transl)].", "content": "Angiography has proved valuable as a method for visualizing the position and extent of trophoblastic tumors. Angiography together with the determination of gonadotropin makes a more exact diagnosis possible and, therefore, an individual therapy. The treatment must be intentionally carried out's the age of the patient plays an important role here. For many cases today, purely conservative therapy with cytostatic drugs is possible. This method was used in 11 female patients with suspected or histologically established trophoblastic tumors. In 4 women, the tumor was suspected a because of the reincrease in HCG excretion following a hydatidiform mole. A metastasizing mole was established histologically in 3 patients and a choriocarcinoma, in 4 patients. A good correspondence was found between angiographic and macroscopic findings in 6 women who underwent surgery. In evaluating control angiograms following chemotherapy, it should be noted that tumors do not recede completely in every case.", "contents": "[Efficacy of angiography for the diagnosis of trophoblastic tumors (author's transl)]. Angiography has proved valuable as a method for visualizing the position and extent of trophoblastic tumors. Angiography together with the determination of gonadotropin makes a more exact diagnosis possible and, therefore, an individual therapy. The treatment must be intentionally carried out's the age of the patient plays an important role here. For many cases today, purely conservative therapy with cytostatic drugs is possible. This method was used in 11 female patients with suspected or histologically established trophoblastic tumors. In 4 women, the tumor was suspected a because of the reincrease in HCG excretion following a hydatidiform mole. A metastasizing mole was established histologically in 3 patients and a choriocarcinoma, in 4 patients. A good correspondence was found between angiographic and macroscopic findings in 6 women who underwent surgery. In evaluating control angiograms following chemotherapy, it should be noted that tumors do not recede completely in every case."}
{"id": "PMID:188723", "title": "Hormone independent in vitro erythroid colony formation by mouse bone marrow cells.", "content": "B.M. cells of RLV-infected BALB/c mice can proliferate in methylcellulose in the absence of E.P., while normal B.M. cells cannot (12). Not only the more primitive BFU-E shows hormone-independency (18). This phenomenon is in favour of the view that the Rauscher virus induced erythroblastosis is a true neoplasia although transplantation experiments failed so far. The experiments in which transformation in vitro of B.M. cells by RLV is established (19) show that the CFU-E can serve as a target for the virus. Treatment of normal mice with CFA leads to a rapid increase in CFU-E in the bone marrow (18). Splenomegaly of RLV-infected mice is enhanced by CFA-treatment probably due to an increase in targets. Transfection with proviral DNA also can transform the CFU-E of BALB-c mice. This approach allows in vitro studies on the resistence of mouse strains to RLV in vitro. The studies are of interest for the human disease in two aspects. In vitro transformation assays are needed to study the oncogenic potential of putative human leukemia viruses. Furthermore the studies have yielded some new insight in the pathogenesis of virally induced erythroblastosis. This might serve as a model for e.g. acute myeloid leukemia in man.", "contents": "Hormone independent in vitro erythroid colony formation by mouse bone marrow cells. B.M. cells of RLV-infected BALB/c mice can proliferate in methylcellulose in the absence of E.P., while normal B.M. cells cannot (12). Not only the more primitive BFU-E shows hormone-independency (18). This phenomenon is in favour of the view that the Rauscher virus induced erythroblastosis is a true neoplasia although transplantation experiments failed so far. The experiments in which transformation in vitro of B.M. cells by RLV is established (19) show that the CFU-E can serve as a target for the virus. Treatment of normal mice with CFA leads to a rapid increase in CFU-E in the bone marrow (18). Splenomegaly of RLV-infected mice is enhanced by CFA-treatment probably due to an increase in targets. Transfection with proviral DNA also can transform the CFU-E of BALB-c mice. This approach allows in vitro studies on the resistence of mouse strains to RLV in vitro. The studies are of interest for the human disease in two aspects. In vitro transformation assays are needed to study the oncogenic potential of putative human leukemia viruses. Furthermore the studies have yielded some new insight in the pathogenesis of virally induced erythroblastosis. This might serve as a model for e.g. acute myeloid leukemia in man."}
{"id": "PMID:188728", "title": "Restricted addition of proviral DNA in target tissues of chickens infected with avian myeloblastosis virus.", "content": "Proviral DNA is synthesized within an hour after infection of chicken cells with an avian oncornavirus and is integrated into nuclear cellular DNA within a short time. The viral DNA appears to be synthesized as double-stranded molecules of approximately 6 X 10(6) daltons some of which are converted into supercoiled cricles perhaps as a requisite for integration. The endogenous v-DNA in normal chicken cells and both the endogenous and amv v-DNA in leukemic chicken myeloblasts are covalently linked with chromosomal DNA. There is no detectable free DNA either circular or linear present in leukemic cells several weeks after infection. The endogenous v-DNA which is transmitted vertically from parents to offspring is uniformly and stably distributed in all chicken organs. There are about 1-2 copies of endogenous provirus per haploid genome of all normal cells. This DNA is very closely related to RAV-O RNA. After infection with AMV it seems that target cells such as leukemic myeloblasts, RBC and nephroblasts acquire complete copies of AMV DNA. Interestingly, only these target cells can be converted to neoplastic cells in the chicken as well as in vitro. The target cells acquire 1-2 copies of AMV specific DNA per haploid genome in addition to the endogenous v-DNA. All the available evidence shows that leukemic and kidney tumor cells have acquired AMV v-DNA. It remains to be elucidated whether the newly added viral DNA is alone responsible for neoplastic changes or does so in conjunction with endogenous viral information.", "contents": "Restricted addition of proviral DNA in target tissues of chickens infected with avian myeloblastosis virus. Proviral DNA is synthesized within an hour after infection of chicken cells with an avian oncornavirus and is integrated into nuclear cellular DNA within a short time. The viral DNA appears to be synthesized as double-stranded molecules of approximately 6 X 10(6) daltons some of which are converted into supercoiled cricles perhaps as a requisite for integration. The endogenous v-DNA in normal chicken cells and both the endogenous and amv v-DNA in leukemic chicken myeloblasts are covalently linked with chromosomal DNA. There is no detectable free DNA either circular or linear present in leukemic cells several weeks after infection. The endogenous v-DNA which is transmitted vertically from parents to offspring is uniformly and stably distributed in all chicken organs. There are about 1-2 copies of endogenous provirus per haploid genome of all normal cells. This DNA is very closely related to RAV-O RNA. After infection with AMV it seems that target cells such as leukemic myeloblasts, RBC and nephroblasts acquire complete copies of AMV DNA. Interestingly, only these target cells can be converted to neoplastic cells in the chicken as well as in vitro. The target cells acquire 1-2 copies of AMV specific DNA per haploid genome in addition to the endogenous v-DNA. All the available evidence shows that leukemic and kidney tumor cells have acquired AMV v-DNA. It remains to be elucidated whether the newly added viral DNA is alone responsible for neoplastic changes or does so in conjunction with endogenous viral information."}
{"id": "PMID:188729", "title": "Sequences and functions of Rous sarcoma virus RNA.", "content": "A procedure has been developed to map the genetic elements of avian tumor virus RNA, which has a molecular weight of about 3 X 10(6) daltons and a poly(A) sequence at the 3' end. For this purpose, about 30 RNase T1-resistant oligonucleotides were ordered relative to the 3'-poly(A) terminus of the RNA, to construct an oligonucleotide map of viral RNAs. A cluster of seven envelope gene (env)-specific oligonucleotides, identified by their absence from the otherwise very similar oligonucleotide map of an envelope-defective deletion mutant (which lacks the major viral glycoprotein), mapped at a distance of 0.9 to 1.6 X 10(6) daltons from the poly(A) end of sarcoma virus RNA. A cluster of three sarcoma gene (src)-specific oligonucleotides, identified by their absence from the otherwise nearly identical oligonucleotide map of a transformation-defective deletion mutant mapped at a distance of 0.2 to 0.6 X 10(6) daltons from the poly(A) end of sarcoma virus RNA. The oligonucleotide maps of sarcoma viruses and of related deletion mutants were the same from the poly(A) end up to 0.2 X 10(6) daltons and included one terminal oligonucleotide, termed C, which is found in all avian tumor viruses tested so far. Preliminary mapping experiments ordering the src-specific and env-specific oligonucleotides of recombinants, selected for sarcoma and envelope genes of different parents, agree with those obtained by comparing maps of wild type viruses and deletion mutants. A partial genetic map consistent with these results suggests that the src gene maps between the env gene and the 3'-poly(A) end of viral RNA. This map reads: poly(A)-src-env-(pol, gag).", "contents": "Sequences and functions of Rous sarcoma virus RNA. A procedure has been developed to map the genetic elements of avian tumor virus RNA, which has a molecular weight of about 3 X 10(6) daltons and a poly(A) sequence at the 3' end. For this purpose, about 30 RNase T1-resistant oligonucleotides were ordered relative to the 3'-poly(A) terminus of the RNA, to construct an oligonucleotide map of viral RNAs. A cluster of seven envelope gene (env)-specific oligonucleotides, identified by their absence from the otherwise very similar oligonucleotide map of an envelope-defective deletion mutant (which lacks the major viral glycoprotein), mapped at a distance of 0.9 to 1.6 X 10(6) daltons from the poly(A) end of sarcoma virus RNA. A cluster of three sarcoma gene (src)-specific oligonucleotides, identified by their absence from the otherwise nearly identical oligonucleotide map of a transformation-defective deletion mutant mapped at a distance of 0.2 to 0.6 X 10(6) daltons from the poly(A) end of sarcoma virus RNA. The oligonucleotide maps of sarcoma viruses and of related deletion mutants were the same from the poly(A) end up to 0.2 X 10(6) daltons and included one terminal oligonucleotide, termed C, which is found in all avian tumor viruses tested so far. Preliminary mapping experiments ordering the src-specific and env-specific oligonucleotides of recombinants, selected for sarcoma and envelope genes of different parents, agree with those obtained by comparing maps of wild type viruses and deletion mutants. A partial genetic map consistent with these results suggests that the src gene maps between the env gene and the 3'-poly(A) end of viral RNA. This map reads: poly(A)-src-env-(pol, gag)."}
{"id": "PMID:188735", "title": "Control of peptide chain initiation in uninfected and virus infected cells by membrane mediated events.", "content": "Initiation of protein synthesis in tissue culture cells is rapidly inhibited or blocked by addition of either DMSO, ethanol, TPCK, cytochalasin B, or sucrose to the growth medium. In contrast, these agents do not interfere with the initiation of protein synthesis in cell-free extracts to a comparable extent. These results support the hypothesis that protein synthesis in tissue culture cells can be influenced by membrane mediated events. Translation of viral mRNA in RNA virus infected cells is resistant to a number of these inhibitors of peptide chain initiation and proceeds under conditions where translation of host mRNA is almost completely suppressed. It appears that viral mRNA possesses a greater ability than host mRNA to form mRNA-ribosome initiation complexes when the overall rate of peptide chain initiation is reduced. This observation has led to a number of predictions concerning the strategy of virus directed suppression of host mRNA translation. Under optimal growth conditions protein synthesis appears to be regulated mainly, but not exclusively, by the amount of the mRNA available for translation. However, when cellular growth and/or the overall rate of peptide chain initiation is restricted, control of protein synthesis at the translational level becomes decisive with the translation of each mRNA species proceeding with its own characteristic efficiency most probably as a result of inherent differential affinities of individual mRNA species for ribosomes.", "contents": "Control of peptide chain initiation in uninfected and virus infected cells by membrane mediated events. Initiation of protein synthesis in tissue culture cells is rapidly inhibited or blocked by addition of either DMSO, ethanol, TPCK, cytochalasin B, or sucrose to the growth medium. In contrast, these agents do not interfere with the initiation of protein synthesis in cell-free extracts to a comparable extent. These results support the hypothesis that protein synthesis in tissue culture cells can be influenced by membrane mediated events. Translation of viral mRNA in RNA virus infected cells is resistant to a number of these inhibitors of peptide chain initiation and proceeds under conditions where translation of host mRNA is almost completely suppressed. It appears that viral mRNA possesses a greater ability than host mRNA to form mRNA-ribosome initiation complexes when the overall rate of peptide chain initiation is reduced. This observation has led to a number of predictions concerning the strategy of virus directed suppression of host mRNA translation. Under optimal growth conditions protein synthesis appears to be regulated mainly, but not exclusively, by the amount of the mRNA available for translation. However, when cellular growth and/or the overall rate of peptide chain initiation is restricted, control of protein synthesis at the translational level becomes decisive with the translation of each mRNA species proceeding with its own characteristic efficiency most probably as a result of inherent differential affinities of individual mRNA species for ribosomes."}
{"id": "PMID:188736", "title": "Proliferation kinetics and cyclic AMP in human leukaemic cells: their relevance to therapy.", "content": "In the cells of acute leukemia the duration of the cell cycle and its phases was determined in vitro by autoradiographic techniques. Tests were run simultaneously for bone marrow and peripheral leukaemic cells and the intracellular levels of cAMP were measured. The results suggest a correlation to exist between cAMP concentration in leukaemic cells and the growth rate of the cell population. Hence, cAMP assays appear to be suited for monitoring cellular proliferation kinetics and could provide a useful parameter for planning cell-phase-specific therapy.", "contents": "Proliferation kinetics and cyclic AMP in human leukaemic cells: their relevance to therapy. In the cells of acute leukemia the duration of the cell cycle and its phases was determined in vitro by autoradiographic techniques. Tests were run simultaneously for bone marrow and peripheral leukaemic cells and the intracellular levels of cAMP were measured. The results suggest a correlation to exist between cAMP concentration in leukaemic cells and the growth rate of the cell population. Hence, cAMP assays appear to be suited for monitoring cellular proliferation kinetics and could provide a useful parameter for planning cell-phase-specific therapy."}
{"id": "PMID:188738", "title": "[Mechanism of anti-inflammatory action of 2-(2-fluoro-4-biphenylyl) propionic acid (flurbiprofen)].", "content": "Anti-inflammatory mechanism of 2-(2-fluoro-4-biphenylyl) propionic acid (Flurbiprofen, FP-70) was studied by various analysis in comparison with other drugs. It was found in the test of rat edema induced by various phlogists that carrageenin and yeast-induced edemas were markedly inhibited by FP-70, whereas dextran, formalin, serotonin and bradykinin-induced edemas were scarcely inhibited by FP-70. The action of FP-70 was similar to that of soy bean trypsin inhibitor. However, FP-70 showed no effects on kinin synthetase and kininase. FP-70 showed a marked inhibition on prostaglandin synthesis. The inhibitory effect of FP-70 was 10.1, 96.5 and 2280.6 times as large as indomethacin, ibuprofen and acetylsalicylic acid, respectively. FP-70 did not inhibit the permeability of dye induced by prostaglandin E2 in the rat skin. FP-70 inhibited the acid phosphatase and beta-glucuronidase activities of isolated lysosome of rat liver and also suppressed the release of acid phosphatase from the lysosome. These effects were similar to those of indomethacin. On the other hand, FP-70 suppressed markedly the heat-induced hemolysis of dog erythrocytes. The effect was similar to that of indomethacin and was 10 times stronger than those of ibuprofen, ibufenac and phenylbutazone. Activation of rat liver mitochondrial ATPase by FP-70 at a concentration of 10 muM was 74.7%, while indomethacin showed 37.8% activation at the same concentration. FP-70 as well as ibuprofen and phenylbutazone uncoupled the oxidative phosphorylation in rat liver mitochondria. From the above and previously reported results, it is suggested that the potent anti-inflammatory action of FP-70 is the result of the following effects; inhibition on the protein and leucocyte migration, inhibition on the prostaglandin synthesis, stabilization of the cell membrane and activation of ATPase.", "contents": "[Mechanism of anti-inflammatory action of 2-(2-fluoro-4-biphenylyl) propionic acid (flurbiprofen)]. Anti-inflammatory mechanism of 2-(2-fluoro-4-biphenylyl) propionic acid (Flurbiprofen, FP-70) was studied by various analysis in comparison with other drugs. It was found in the test of rat edema induced by various phlogists that carrageenin and yeast-induced edemas were markedly inhibited by FP-70, whereas dextran, formalin, serotonin and bradykinin-induced edemas were scarcely inhibited by FP-70. The action of FP-70 was similar to that of soy bean trypsin inhibitor. However, FP-70 showed no effects on kinin synthetase and kininase. FP-70 showed a marked inhibition on prostaglandin synthesis. The inhibitory effect of FP-70 was 10.1, 96.5 and 2280.6 times as large as indomethacin, ibuprofen and acetylsalicylic acid, respectively. FP-70 did not inhibit the permeability of dye induced by prostaglandin E2 in the rat skin. FP-70 inhibited the acid phosphatase and beta-glucuronidase activities of isolated lysosome of rat liver and also suppressed the release of acid phosphatase from the lysosome. These effects were similar to those of indomethacin. On the other hand, FP-70 suppressed markedly the heat-induced hemolysis of dog erythrocytes. The effect was similar to that of indomethacin and was 10 times stronger than those of ibuprofen, ibufenac and phenylbutazone. Activation of rat liver mitochondrial ATPase by FP-70 at a concentration of 10 muM was 74.7%, while indomethacin showed 37.8% activation at the same concentration. FP-70 as well as ibuprofen and phenylbutazone uncoupled the oxidative phosphorylation in rat liver mitochondria. From the above and previously reported results, it is suggested that the potent anti-inflammatory action of FP-70 is the result of the following effects; inhibition on the protein and leucocyte migration, inhibition on the prostaglandin synthesis, stabilization of the cell membrane and activation of ATPase."}
{"id": "PMID:188740", "title": "Angiographic findings in some rare pancreatic tumors.", "content": "Angiographic findings in one giant cell carcinoma, one cystadenocarcinoma, one poorly vascularized mucinous cystadenocarcinoma, as well as in two avascular (gastrin- and glucagon-producing) islet-cell tumors of the pancreas are described. Two hypervascularized islet-cell tumors are presented for comparison and a case of tumorous chronic pancreatitis in a child is reported because ot its rarity. The aggressiveness of the giant cell carcinoma of the pancreas was demonstrated by its expansive growth. In the case of cystadenocarcinoma angiography revealed the tumor with hepatic metastases not diagnosed at explorative laparotomy. The relative hypovascularity in the case of mucinous cystadenocarcinoma was unusual. Both avascular islet-cell tumors simulated a pancreatic pseudocyst and the final diagnosis was made only by immunoassay. Chronic pancreatitis in a child presented with marked hypervascularization.", "contents": "Angiographic findings in some rare pancreatic tumors. Angiographic findings in one giant cell carcinoma, one cystadenocarcinoma, one poorly vascularized mucinous cystadenocarcinoma, as well as in two avascular (gastrin- and glucagon-producing) islet-cell tumors of the pancreas are described. Two hypervascularized islet-cell tumors are presented for comparison and a case of tumorous chronic pancreatitis in a child is reported because ot its rarity. The aggressiveness of the giant cell carcinoma of the pancreas was demonstrated by its expansive growth. In the case of cystadenocarcinoma angiography revealed the tumor with hepatic metastases not diagnosed at explorative laparotomy. The relative hypovascularity in the case of mucinous cystadenocarcinoma was unusual. Both avascular islet-cell tumors simulated a pancreatic pseudocyst and the final diagnosis was made only by immunoassay. Chronic pancreatitis in a child presented with marked hypervascularization."}
{"id": "PMID:188742", "title": "Who gets aftercare? A study of patients discharged from state hospitals in Kentucky.", "content": "A cohort of 579 patients discharged from state mental hospitals in Kentucky during a one-year period was studied to determine the amount and nature of after-care services provided to them. A total of 319 received some form of attercare from community mental health centers during the two to three years after discharge. The majority received at least one service that could be classified as individual therapy or chemotherapy, about one-third received evaluation or rehabilitation services, and only a few had family interviews or group therapy. The majority of those receiving services had contact with psychiatrists, nurses, or other mental health professionals; less than half had contact with social workers or psychologists. In general the aftercare services tended to be medically oriented, brief, and limited in number. They were provided to a majority of the patients within their first month in the community.", "contents": "Who gets aftercare? A study of patients discharged from state hospitals in Kentucky. A cohort of 579 patients discharged from state mental hospitals in Kentucky during a one-year period was studied to determine the amount and nature of after-care services provided to them. A total of 319 received some form of attercare from community mental health centers during the two to three years after discharge. The majority received at least one service that could be classified as individual therapy or chemotherapy, about one-third received evaluation or rehabilitation services, and only a few had family interviews or group therapy. The majority of those receiving services had contact with psychiatrists, nurses, or other mental health professionals; less than half had contact with social workers or psychologists. In general the aftercare services tended to be medically oriented, brief, and limited in number. They were provided to a majority of the patients within their first month in the community."}
{"id": "PMID:188743", "title": "Community aftercare of patients discharged from Utah state hospital: a follow-up study.", "content": "To find out whether patients discharged from mental hospitals to the community are following recommended courses of aftercare treatment, the authors, with the assistance of five medical students, studied a sample of patients discharged from Utah State Hospital during 1973 and 1974. The discharge plans of 143 patients admitted from Salt Lake County indicated that 125 of them should have received aftercare services from a community mental health center. A review of CMHC records and interviews with the patients indicated that only 100 actually had contact with a center. Only 43 of the patients were still receiving aftercare services in the summer of 1975.", "contents": "Community aftercare of patients discharged from Utah state hospital: a follow-up study. To find out whether patients discharged from mental hospitals to the community are following recommended courses of aftercare treatment, the authors, with the assistance of five medical students, studied a sample of patients discharged from Utah State Hospital during 1973 and 1974. The discharge plans of 143 patients admitted from Salt Lake County indicated that 125 of them should have received aftercare services from a community mental health center. A review of CMHC records and interviews with the patients indicated that only 100 actually had contact with a center. Only 43 of the patients were still receiving aftercare services in the summer of 1975."}
{"id": "PMID:188744", "title": "Aftercare of psychiatric patients and its relation to rehospitalization.", "content": "In their study of the effects of posthospital treatment on psychiatric patients the authors found that those who entered aftercare were rehospitalized less often than those who did not. They found the rehospitalization rate was higher for schizophrenic patients than for patients in other diagnostic groups, and that schizophrenic patients who did not enter aftercare were rehospitalized at a higher rate than those who did. They found no difference between rehospitalization rates of patients who continued with their hospital therapist after discharge and those patients who worked with a new therapist.", "contents": "Aftercare of psychiatric patients and its relation to rehospitalization. In their study of the effects of posthospital treatment on psychiatric patients the authors found that those who entered aftercare were rehospitalized less often than those who did not. They found the rehospitalization rate was higher for schizophrenic patients than for patients in other diagnostic groups, and that schizophrenic patients who did not enter aftercare were rehospitalized at a higher rate than those who did. They found no difference between rehospitalization rates of patients who continued with their hospital therapist after discharge and those patients who worked with a new therapist."}
{"id": "PMID:188745", "title": "Transitional care: a new approach to aftercare.", "content": "The transitional-care program incorporates the principles of behavior modification and group and family therapy in order to help recently discharged psychiatric patients maintain the positive changes that occurred in the hospital. Patients meet for approximately three hours a week, for up to 12 weeks, with nursing staff who worked with them while they were hospitalized. Each patient has an individual treatment program and goals, and during meetings with his team he discusses his progress and problems in meeting those goals. Staff members encourage patients to accept responsibility for each other and not to become too dependent on them. The program has been successful in preventing rehospitalization.", "contents": "Transitional care: a new approach to aftercare. The transitional-care program incorporates the principles of behavior modification and group and family therapy in order to help recently discharged psychiatric patients maintain the positive changes that occurred in the hospital. Patients meet for approximately three hours a week, for up to 12 weeks, with nursing staff who worked with them while they were hospitalized. Each patient has an individual treatment program and goals, and during meetings with his team he discusses his progress and problems in meeting those goals. Staff members encourage patients to accept responsibility for each other and not to become too dependent on them. The program has been successful in preventing rehospitalization."}
{"id": "PMID:188746", "title": "Pharmacological aftercare for homogeneous groups of patients.", "content": "In a study to evaluate the effectiveness of specific pharmacological treatment groups, former VA inpatients who have similar diagnoses and respond satisfatorily to drug treatment join a Prolixin group, a lithium group, or an affective disorder group. In monthly meetings patients learn about their illness, the importance of the taking medication as prescribed, and possible side-effects; they also receive psychological support. The 85 patients who joined the groups during the first 12 months attended 87.3 per cent of the sessions. Twenty per cent of them were rehospitalized, about half of them because they did not take medication as prescribed. The authors believe the groups are an economical and effective way to provide aftercare.", "contents": "Pharmacological aftercare for homogeneous groups of patients. In a study to evaluate the effectiveness of specific pharmacological treatment groups, former VA inpatients who have similar diagnoses and respond satisfatorily to drug treatment join a Prolixin group, a lithium group, or an affective disorder group. In monthly meetings patients learn about their illness, the importance of the taking medication as prescribed, and possible side-effects; they also receive psychological support. The 85 patients who joined the groups during the first 12 months attended 87.3 per cent of the sessions. Twenty per cent of them were rehospitalized, about half of them because they did not take medication as prescribed. The authors believe the groups are an economical and effective way to provide aftercare."}
{"id": "PMID:188752", "title": "Spontaneous contractions of dispersed vascular muscle in cell culture.", "content": "Dispersed vascular muscle cells from chick omphalomesenteric vessels maintained in primary cell culture contracted spontaneously. Six methods which produced contracting isolated muscle cells are described and compared. The combination of dispersion method and culture conditions to produce contracting muscle cells was more critical for vascular than for heart muscle. These findings of continuing pacemaker function demonstrate that functional integrity of isolated vascular muscle cells is possible to maintain. Further indication of the full functional state of the isolated vascular muscle cells was demonstrated by the sensitivity to norepinephrine at a physiological concentration (0.1 muM). Spontaneous contraction frequencies were similar to the range found in situ, and spontanious or norepinephrine-induced contractions had time courses corresponding to intact vessel contractions. This is the first report that isolated vascular muscle cells in primary cell culture retain functional characteristics found in situ and are suitable for pharmacological characterization of individual muscle cells.", "contents": "Spontaneous contractions of dispersed vascular muscle in cell culture. Dispersed vascular muscle cells from chick omphalomesenteric vessels maintained in primary cell culture contracted spontaneously. Six methods which produced contracting isolated muscle cells are described and compared. The combination of dispersion method and culture conditions to produce contracting muscle cells was more critical for vascular than for heart muscle. These findings of continuing pacemaker function demonstrate that functional integrity of isolated vascular muscle cells is possible to maintain. Further indication of the full functional state of the isolated vascular muscle cells was demonstrated by the sensitivity to norepinephrine at a physiological concentration (0.1 muM). Spontaneous contraction frequencies were similar to the range found in situ, and spontanious or norepinephrine-induced contractions had time courses corresponding to intact vessel contractions. This is the first report that isolated vascular muscle cells in primary cell culture retain functional characteristics found in situ and are suitable for pharmacological characterization of individual muscle cells."}
{"id": "PMID:188753", "title": "Banded karyotypes of H-4-IIE-C3 rat hepatoma cells grown in vitro.", "content": "Mitotic cells from the H-4-IIE-C3 rat hepatoma tissue culture line showed a range of 45 to 53 chromosomes per cell with 75% of the cells displaying a chromosome mumber between 49 and 52. Analysis of Wright's-Giemsa banded karyotypes of 22 cells revealed considerable cell to cell variation. Twenty-one structurally abnormal chromosomes were identified in these cells; the origin of nine of the 21 chromosomes were identified in these cells; the origin of nine of the 21 chromosomes could be determined. Of the structurally abnormal chromosomes detected, only one (M-1) occurred with a sufficiently high frequency to be of general use as a marker for these cells. This marker appears to be a Robertsonian translocation involving chromosome number 2 and chromosome number 10.", "contents": "Banded karyotypes of H-4-IIE-C3 rat hepatoma cells grown in vitro. Mitotic cells from the H-4-IIE-C3 rat hepatoma tissue culture line showed a range of 45 to 53 chromosomes per cell with 75% of the cells displaying a chromosome mumber between 49 and 52. Analysis of Wright's-Giemsa banded karyotypes of 22 cells revealed considerable cell to cell variation. Twenty-one structurally abnormal chromosomes were identified in these cells; the origin of nine of the 21 chromosomes were identified in these cells; the origin of nine of the 21 chromosomes could be determined. Of the structurally abnormal chromosomes detected, only one (M-1) occurred with a sufficiently high frequency to be of general use as a marker for these cells. This marker appears to be a Robertsonian translocation involving chromosome number 2 and chromosome number 10."}
{"id": "PMID:188760", "title": "Mechanism of action of Pseudomonas aeruginosa exotoxin Aiadenosine diphosphate-ribosylation of mammalian elongation factor 2 in vitro and in vivo.", "content": "Previous studies showed that Pseudomonas aeruginosa exotoxin A (PA toxin) catalyzes nicotinamide adenine dinucleotide (NAD)-dependent inhibition of protein synthesis in a rabbit reticulocyte lysate and transfer of radioactivity from [14C]adenine-labeled NAD to a protein having the same molecular weight as elongation factor 2 (EF-2) (B.H. Iglewski and D. Kabat, 1975). Such an inhibited protein-synthesizing lysate was restored to activity by addition of a protein from normal mouse liver which co-purifies with EF-2. In addition, EF-2 activity was almost totally absent in livers of mice which had been injected 24 h earlier with PA toxin. On the contrary, EF-2 concentrations were only partially reduced in other organs and were normal in brains of intoxicated mice. Studies using NAD labeled in various positions show that PA toxin, like fragment A of diphtheria toxin, catalyzes transfer of the adenosine 5'-diphosphate-ribosyl moiety of NAD. Furthermore, reversal occurred when the modified protein was incubated with excess concentrations of PA toxin and nicotinamide, and NAD was identified as a product of the reverse reaction. The protein modification catalyzed either by PA toxin or by fragment A of diphtheria toxin could be reversed by incubation with other toxin. These results support the proposal that these two toxins adenosine 5'-diphosphate-ribosylate and same amino acid of EF-2 in a stereochemically identical fashion. Furthermore, PA toxin inactivates EF-2 in intoxicated mice to an extent which would ultimately result in death.", "contents": "Mechanism of action of Pseudomonas aeruginosa exotoxin Aiadenosine diphosphate-ribosylation of mammalian elongation factor 2 in vitro and in vivo. Previous studies showed that Pseudomonas aeruginosa exotoxin A (PA toxin) catalyzes nicotinamide adenine dinucleotide (NAD)-dependent inhibition of protein synthesis in a rabbit reticulocyte lysate and transfer of radioactivity from [14C]adenine-labeled NAD to a protein having the same molecular weight as elongation factor 2 (EF-2) (B.H. Iglewski and D. Kabat, 1975). Such an inhibited protein-synthesizing lysate was restored to activity by addition of a protein from normal mouse liver which co-purifies with EF-2. In addition, EF-2 activity was almost totally absent in livers of mice which had been injected 24 h earlier with PA toxin. On the contrary, EF-2 concentrations were only partially reduced in other organs and were normal in brains of intoxicated mice. Studies using NAD labeled in various positions show that PA toxin, like fragment A of diphtheria toxin, catalyzes transfer of the adenosine 5'-diphosphate-ribosyl moiety of NAD. Furthermore, reversal occurred when the modified protein was incubated with excess concentrations of PA toxin and nicotinamide, and NAD was identified as a product of the reverse reaction. The protein modification catalyzed either by PA toxin or by fragment A of diphtheria toxin could be reversed by incubation with other toxin. These results support the proposal that these two toxins adenosine 5'-diphosphate-ribosylate and same amino acid of EF-2 in a stereochemically identical fashion. Furthermore, PA toxin inactivates EF-2 in intoxicated mice to an extent which would ultimately result in death."}
{"id": "PMID:188761", "title": "Frentizole, a novel immunosuppressive, and azathioprine: their comparative effects on host resistance to Pseudomonas aeruginosa, Candida albicans, herpes simplex virus, and influenza (Ann Arbor) virus.", "content": "Frentizole, 1-(6-methoxy-2-benzothiazolyl)-3-phenyl urea, a new immunosuppressive agent, and azathioprine were administered subcutaneously at predetermined immunosuppressive dose levels of azathioprine and up to 50 times an immunosuppressive dose level of Frentizole. After 10 days of treatment at these dose levels, the experimental groups were inoculated intraperitoneally with Pseudomonas aeruginosa or herpes simplex virus, inoculated intraveneously with Candida albicans, or infected by aerosol with Ann Arbor influenza virus. The results of these series of experiments indicate that Frentizole, even at super immunosuppressive doses, does not predispose the hose (mice) to Pseudomonas aeruginosa, Candida albicans, herpes simplex virus, or Ann Arbor influenza virus.", "contents": "Frentizole, a novel immunosuppressive, and azathioprine: their comparative effects on host resistance to Pseudomonas aeruginosa, Candida albicans, herpes simplex virus, and influenza (Ann Arbor) virus. Frentizole, 1-(6-methoxy-2-benzothiazolyl)-3-phenyl urea, a new immunosuppressive agent, and azathioprine were administered subcutaneously at predetermined immunosuppressive dose levels of azathioprine and up to 50 times an immunosuppressive dose level of Frentizole. After 10 days of treatment at these dose levels, the experimental groups were inoculated intraperitoneally with Pseudomonas aeruginosa or herpes simplex virus, inoculated intraveneously with Candida albicans, or infected by aerosol with Ann Arbor influenza virus. The results of these series of experiments indicate that Frentizole, even at super immunosuppressive doses, does not predispose the hose (mice) to Pseudomonas aeruginosa, Candida albicans, herpes simplex virus, or Ann Arbor influenza virus."}
{"id": "PMID:188762", "title": "Herpes simplex virus infections in guinea pigs deficient in the fourth component of complement.", "content": "Separate groups of normal and C4-deficient guinea pigs were inoculated with herpes simplex virus by intradermal (i.d.) and intraperitoneal (i.p.) routes. Virus infection, confirmed by clinical, virological, and serological criteria, did not last longer and was not more severe in C4-deficient guinea pigs than in normal guinea pigs. Serum C component levels were measured before, during, and after herpes simplex virus infection. In normal gruinea pigs there was no evidence for C4 utilization after either i.d. or i.p. inoculation. In both normal and C4-deficient guinea pigs, C1 and C3-9 levels remained unchanged in spite of i.d. or i.p. infection. These data suggested that C4 and the classical C pathway were not important for virus clearance.", "contents": "Herpes simplex virus infections in guinea pigs deficient in the fourth component of complement. Separate groups of normal and C4-deficient guinea pigs were inoculated with herpes simplex virus by intradermal (i.d.) and intraperitoneal (i.p.) routes. Virus infection, confirmed by clinical, virological, and serological criteria, did not last longer and was not more severe in C4-deficient guinea pigs than in normal guinea pigs. Serum C component levels were measured before, during, and after herpes simplex virus infection. In normal gruinea pigs there was no evidence for C4 utilization after either i.d. or i.p. inoculation. In both normal and C4-deficient guinea pigs, C1 and C3-9 levels remained unchanged in spite of i.d. or i.p. infection. These data suggested that C4 and the classical C pathway were not important for virus clearance."}
{"id": "PMID:188763", "title": "Stable L-forms of Clostridium perfringens: growth, toxin production, and pathogenicity.", "content": "Growth and toxin production of stable L-forms of Clostridium perfringens grown in a mini-fermentor were monitored. A gradual but steady increment in viable count occurred over a 7-h period, followed by death. The peak of viability preceded the optical density peak by 3 h. Theta, alpha, kappa, and lambda toxins were measured, with theta toxin appearing first in the culture supernate. Growth of the parent bacillus form of C. perfringens was compared under similar conditions. Toxin levels achieved by the bacillus culture exceeded those of the L-form culture four- to eightfold; however, based upon viable count, the L-form organism produced 8 to 16 times as much toxin as did the bacillus. The amounts of extracellular toxin produced by both forms were similar when related to cell protein rather than cell number. Guinea pig inoculation showed that the L-form of C. perfringens did not produce gas gangrene, although it was not entirely without effect. Both guinea pig and human sera were inhibitory to these L-forms, a fact attributable to a heat-liable component in the sera, most likely complement.", "contents": "Stable L-forms of Clostridium perfringens: growth, toxin production, and pathogenicity. Growth and toxin production of stable L-forms of Clostridium perfringens grown in a mini-fermentor were monitored. A gradual but steady increment in viable count occurred over a 7-h period, followed by death. The peak of viability preceded the optical density peak by 3 h. Theta, alpha, kappa, and lambda toxins were measured, with theta toxin appearing first in the culture supernate. Growth of the parent bacillus form of C. perfringens was compared under similar conditions. Toxin levels achieved by the bacillus culture exceeded those of the L-form culture four- to eightfold; however, based upon viable count, the L-form organism produced 8 to 16 times as much toxin as did the bacillus. The amounts of extracellular toxin produced by both forms were similar when related to cell protein rather than cell number. Guinea pig inoculation showed that the L-form of C. perfringens did not produce gas gangrene, although it was not entirely without effect. Both guinea pig and human sera were inhibitory to these L-forms, a fact attributable to a heat-liable component in the sera, most likely complement."}
{"id": "PMID:188764", "title": "Interferon induction by radioprotective mercaptoalkylamines and derived thiophosphates.", "content": "Radioprotective thiols (five mercaptoalkylamines and four derived thiophosphates) induced interferon and resistance to virus infection. Interferon production occurred in human and mouse nonlymphoid cell cultures. One of the thiols, S,2-aminoethylisothiourea, given intraperitoneally, protected mice against two unrelated viruses--Semliki forest virus and Herpesvirus hominis type 1. Two structurally different radioprotective thiols--the disulfide cystamine and L-cysteine--were unable to induce the firus resistance state or interferon.", "contents": "Interferon induction by radioprotective mercaptoalkylamines and derived thiophosphates. Radioprotective thiols (five mercaptoalkylamines and four derived thiophosphates) induced interferon and resistance to virus infection. Interferon production occurred in human and mouse nonlymphoid cell cultures. One of the thiols, S,2-aminoethylisothiourea, given intraperitoneally, protected mice against two unrelated viruses--Semliki forest virus and Herpesvirus hominis type 1. Two structurally different radioprotective thiols--the disulfide cystamine and L-cysteine--were unable to induce the firus resistance state or interferon."}
{"id": "PMID:188765", "title": "Expression of Aleutian mink disease antigen in cell culture.", "content": "Infection of CRFK feline kidney cells with Aleutian disease vurus leads to production of virus-induced antigen(s) in the nucleus which could be demonstrated by the fluorescent-antibody technique. The number of fluorescent nuclei was lineraly dependent on the dilution of the inoculum, but rarely exceeded 20% of the cells. Aleutian disease nuclear antigen was only transiently detectable. The virus-induced antigen was detected after infection of cells of several divergent species; however, the CRFK line of feline kidney cells was the most susceptible. Inhibitor studies indicated that deoxyribonucleic acid synthesis, ribonucleic acid synthesis, and protein synthesis were required for viral antigen production. Cell growth was also a requirement for synthesis of viral antigen, An in situ radioimmune assay was used to measure binding of 125I-labeled mink anti-Aleutian disease virus to infected cells and competition with unlabeled sera. The system is suitable for quantitation of infectivity.", "contents": "Expression of Aleutian mink disease antigen in cell culture. Infection of CRFK feline kidney cells with Aleutian disease vurus leads to production of virus-induced antigen(s) in the nucleus which could be demonstrated by the fluorescent-antibody technique. The number of fluorescent nuclei was lineraly dependent on the dilution of the inoculum, but rarely exceeded 20% of the cells. Aleutian disease nuclear antigen was only transiently detectable. The virus-induced antigen was detected after infection of cells of several divergent species; however, the CRFK line of feline kidney cells was the most susceptible. Inhibitor studies indicated that deoxyribonucleic acid synthesis, ribonucleic acid synthesis, and protein synthesis were required for viral antigen production. Cell growth was also a requirement for synthesis of viral antigen, An in situ radioimmune assay was used to measure binding of 125I-labeled mink anti-Aleutian disease virus to infected cells and competition with unlabeled sera. The system is suitable for quantitation of infectivity."}
{"id": "PMID:188766", "title": "Cell-mediated immunity to Sendai virus infection in mice.", "content": "The development of a cell-mediated immune response to Sendai virus infection in mice was examined by the use of a 51Cr release assay of cytotoxicity. A low level of \"background cytotoxicity\" to Sendai virus-infected L cells was found in the spleens of uninfected CBA mice. Spleen cells from Sendai-infected mice showed an elevated level of cytotoxicity against these target cells for a period of 5 weeks, commencing 4 days after infection of the mice. A more transient response was observed in the spleens of mice infected with a serologically distinct virus, the Kunz strain of influenza. This cross-reacting, cell-mediated immune response was intermediate between that observed in unsensitized and Sendai-sensitized spleen cells. The relevance of these cell-mediated immune responses to respiratory tract virus infections is discussed.", "contents": "Cell-mediated immunity to Sendai virus infection in mice. The development of a cell-mediated immune response to Sendai virus infection in mice was examined by the use of a 51Cr release assay of cytotoxicity. A low level of \"background cytotoxicity\" to Sendai virus-infected L cells was found in the spleens of uninfected CBA mice. Spleen cells from Sendai-infected mice showed an elevated level of cytotoxicity against these target cells for a period of 5 weeks, commencing 4 days after infection of the mice. A more transient response was observed in the spleens of mice infected with a serologically distinct virus, the Kunz strain of influenza. This cross-reacting, cell-mediated immune response was intermediate between that observed in unsensitized and Sendai-sensitized spleen cells. The relevance of these cell-mediated immune responses to respiratory tract virus infections is discussed."}
{"id": "PMID:188767", "title": "Increased histamine sensitivity in mice after administration of endotoxins.", "content": "CFW mice given submicrogram doses of endotoxins intravenously became highly susceptible to the lethal effects of 0.5 mg of histamine given intraperitoneally 1 to 2 h later. The histamine-sensitizing effects of the endotoxins were transitory and disappeared within 6 to 8 h. L-Epinephrine administered intravenously immediately after histamine challenge protected mice from death, but aterenol and isoproterenol were ineffective. The histamine-sensitizing effect in endotoxins was precipitated by anti-endotoxin sera with a concomitant eightfold loss in activity. However, dissociation of the immune complex in 0.25 M acetic acid fully restored histamine-sensitizing activity. The transitory nature of the hypersensitivity produced by endotoxin and the high heat resistance of the active material prove that it is different from the histamine-sensitizing effects of pertussigen.", "contents": "Increased histamine sensitivity in mice after administration of endotoxins. CFW mice given submicrogram doses of endotoxins intravenously became highly susceptible to the lethal effects of 0.5 mg of histamine given intraperitoneally 1 to 2 h later. The histamine-sensitizing effects of the endotoxins were transitory and disappeared within 6 to 8 h. L-Epinephrine administered intravenously immediately after histamine challenge protected mice from death, but aterenol and isoproterenol were ineffective. The histamine-sensitizing effect in endotoxins was precipitated by anti-endotoxin sera with a concomitant eightfold loss in activity. However, dissociation of the immune complex in 0.25 M acetic acid fully restored histamine-sensitizing activity. The transitory nature of the hypersensitivity produced by endotoxin and the high heat resistance of the active material prove that it is different from the histamine-sensitizing effects of pertussigen."}
{"id": "PMID:188768", "title": "DNA binding and its relationship to carcinogenesis by different polycyclic hydrocarbons.", "content": "Five different polycyclic hydrocarbons with different degrees of carcinogenicity in vivo were tested for their metabolism to water-soluble products and their binding to DNA, RNA, and protein in normal embryonic hamster and BHK cells. The compounds studied were 7, 12-dimethylbenz(a)anthracene, benzo(a)pyrene, 20-methyl-cholanthrene, dibenz(a,h)anthracene and dibenz(a,c)anthracene. All five compounds were metabolized to water-soluble produces in both types of cells and treatment of cells with aminophylline enhanced this metabolism. After and not before this enhancement of metabolism by aminophylline, there was a relationship between the degree of carcinogenicity and binding to DNA. There was no such relationship with binding to RNA or protein. The results, indicating a relationship between the degree of carcinogenicity and binding to DNA under appropriate conditions of metabolism, support the suggestion that DNA is the target for carcinogenesis by such carcinogens.", "contents": "DNA binding and its relationship to carcinogenesis by different polycyclic hydrocarbons. Five different polycyclic hydrocarbons with different degrees of carcinogenicity in vivo were tested for their metabolism to water-soluble products and their binding to DNA, RNA, and protein in normal embryonic hamster and BHK cells. The compounds studied were 7, 12-dimethylbenz(a)anthracene, benzo(a)pyrene, 20-methyl-cholanthrene, dibenz(a,h)anthracene and dibenz(a,c)anthracene. All five compounds were metabolized to water-soluble produces in both types of cells and treatment of cells with aminophylline enhanced this metabolism. After and not before this enhancement of metabolism by aminophylline, there was a relationship between the degree of carcinogenicity and binding to DNA. There was no such relationship with binding to RNA or protein. The results, indicating a relationship between the degree of carcinogenicity and binding to DNA under appropriate conditions of metabolism, support the suggestion that DNA is the target for carcinogenesis by such carcinogens."}
{"id": "PMID:188769", "title": "Establishment in continuous culture of a new type of lymphocyte from a \"Burkitt like\" malignant lymphoma (line D.G.-75).", "content": "The isolation and establishment in vitro of a hitherto undescribed type of lymphocyte designated D.G.-75 is reported. The original inoculum was derived from the pleural effusion of a child with a primary abdominal lymphoma, which clinically and histologically resembled Burkitt's lymphoma. In addition to the absence of the EBV genome and EBV receptors, this line possesses a number of other properties which distinguish it from previously described lymphoblastoid cell lines. It has different growth characteristics and morphology; does not form EAC or E rosettes (representative of B and T) cell surface markers, respectively); possesses IgM-kappa immunoglobulins on the cell surface (B lymphocyte), has an unusually high cap-forming ability and low agglutinability with fluorescent concanavalin A. One homologue of the No.14 chromosome pair possesses extra chromatin material as revealed on chromosome banding. This abnormal chromosome marker is similar to that described in biopsies and cultured tumor cells from patients with African Burkitt's lymphoma.", "contents": "Establishment in continuous culture of a new type of lymphocyte from a \"Burkitt like\" malignant lymphoma (line D.G.-75). The isolation and establishment in vitro of a hitherto undescribed type of lymphocyte designated D.G.-75 is reported. The original inoculum was derived from the pleural effusion of a child with a primary abdominal lymphoma, which clinically and histologically resembled Burkitt's lymphoma. In addition to the absence of the EBV genome and EBV receptors, this line possesses a number of other properties which distinguish it from previously described lymphoblastoid cell lines. It has different growth characteristics and morphology; does not form EAC or E rosettes (representative of B and T) cell surface markers, respectively); possesses IgM-kappa immunoglobulins on the cell surface (B lymphocyte), has an unusually high cap-forming ability and low agglutinability with fluorescent concanavalin A. One homologue of the No.14 chromosome pair possesses extra chromatin material as revealed on chromosome banding. This abnormal chromosome marker is similar to that described in biopsies and cultured tumor cells from patients with African Burkitt's lymphoma."}
{"id": "PMID:188770", "title": "A case control study on immunity to two Epstein-Barr virus-associated antigens, and to herpes simplex virus and adenovirus in a population-based group of patients with Hodgkin's disease in Denmark, 1971-73.", "content": "One hundred and eighty-five patients with untreated Hodgkin's disease (HD) comprising 86% of all new cases diagnosed in Denmark over a 2-year period, were individually matched with healthy controls of the same age, sex, and social class. In comparison to controls, HD patients showed significantly elevated mean antibody titres to Epstein-Barr viral capsid antierences in mean titres were found for adenovirus common antigen. Subdivision of the patients by age, sex, social class, HL-A antigens, stage of disease and histology did not alter this pattern, except that significant case-control differences in EB-VCA titres could be demonstrated only for the nodular sclerosis and lymphocyte predominance subgroups. After 1 year of treatment, a significant rise in EB-VCA mean titre had taken place. Splenectomy seemed to promote this titre elevation. Neither the initial titres to EB-VCA and EBV-EA nor changes in titres over time were related to prognosis. The results of our study, which are more representative of a population of HD patients and controls than previously reported studies, confirm that the reported relationship between EBV and HD exists, but that the elevated EBV titres are probably not of etiologic significance in most HD patients.", "contents": "A case control study on immunity to two Epstein-Barr virus-associated antigens, and to herpes simplex virus and adenovirus in a population-based group of patients with Hodgkin's disease in Denmark, 1971-73. One hundred and eighty-five patients with untreated Hodgkin's disease (HD) comprising 86% of all new cases diagnosed in Denmark over a 2-year period, were individually matched with healthy controls of the same age, sex, and social class. In comparison to controls, HD patients showed significantly elevated mean antibody titres to Epstein-Barr viral capsid antierences in mean titres were found for adenovirus common antigen. Subdivision of the patients by age, sex, social class, HL-A antigens, stage of disease and histology did not alter this pattern, except that significant case-control differences in EB-VCA titres could be demonstrated only for the nodular sclerosis and lymphocyte predominance subgroups. After 1 year of treatment, a significant rise in EB-VCA mean titre had taken place. Splenectomy seemed to promote this titre elevation. Neither the initial titres to EB-VCA and EBV-EA nor changes in titres over time were related to prognosis. The results of our study, which are more representative of a population of HD patients and controls than previously reported studies, confirm that the reported relationship between EBV and HD exists, but that the elevated EBV titres are probably not of etiologic significance in most HD patients."}
{"id": "PMID:188771", "title": "Detection of human C-type \"helper\" viruses in human leukemic bone marrow with murine sarcoma virus-transformed human and rat non-producer cells.", "content": "Bone-marrow cells from two leukemic children were co-cultivated with the leukemic children A 7573. In early passages, C-type oncornaviruses were released as detected by extracellular reverse transcriptase assay. Co-cultivation of the infected canine cells with the non-producing cell lines R-970-5 (human) or K-NRK (rat) both transformed by Kirsten mouse sarcoma virus (MSV) yielded a new pseudotype of MSV that could transform rat embryo, rabbit SIRC and human kidney cells but not mouse embryo cells. The focur formation could be inhibited by an antiserum to the simian sarcoma virus but not by a serum directed against murine leukemia virus. A cell line derived from a focus of transformed cells became a highe virus is related to the simian sarcoma virus. It is concluded that the leukemic bone-marrow cells produce a C-type oncornavirus that can serve as a helper virus to the defective MSV.", "contents": "Detection of human C-type \"helper\" viruses in human leukemic bone marrow with murine sarcoma virus-transformed human and rat non-producer cells. Bone-marrow cells from two leukemic children were co-cultivated with the leukemic children A 7573. In early passages, C-type oncornaviruses were released as detected by extracellular reverse transcriptase assay. Co-cultivation of the infected canine cells with the non-producing cell lines R-970-5 (human) or K-NRK (rat) both transformed by Kirsten mouse sarcoma virus (MSV) yielded a new pseudotype of MSV that could transform rat embryo, rabbit SIRC and human kidney cells but not mouse embryo cells. The focur formation could be inhibited by an antiserum to the simian sarcoma virus but not by a serum directed against murine leukemia virus. A cell line derived from a focus of transformed cells became a highe virus is related to the simian sarcoma virus. It is concluded that the leukemic bone-marrow cells produce a C-type oncornavirus that can serve as a helper virus to the defective MSV."}
{"id": "PMID:188772", "title": "Transformation of cultured rat adrenocortical cells by Kirsten murine sarcoma virus (Ki-MSV).", "content": "Two-week-old primary cultures of normal adult rat adrenal cortex were exposed to Kirsten murine sarcoma virus (KiMSV). Within a week, the adrenal cells, which are normally fusiform and aligned in parallel, became pleomorphic and piled up extensively. Saturation density increased from 5-10 x 10(4) to 5-10 x 10(5) cells/cm2, population doubling time during exponential growth decreased from 36-40 to 16h, acid production increased and the growth rate became independent of a reduction in serum concentration from 10% to 1%. Inoculation of 2 x 10(6) of these transformed cells into immuno-depressed rats produced rapidly growing tumors within 1 week. Histologically, the tumors were pleomorphic carcinomas with areas ranging from anaplasia to near-normal, highly differentiated adrenocortical tissue. In addition to histologic evidence of differentiation, metabolic studies using 14C-prognenolone showed that the transformed cells were capable of 20alpha reduction and delta5,3beta dehydrogenation, both characteristic of normal steroid-secreting tissues. The transformed adrenocortical cells produced infectious C-type virus as indicated by electron microscopy, 3H-uridine incorporation, and focus formation in NRK (normal rat kidney) cultures. The neutralization pattern of this virus resembled that of authentic Ki-MSV. The transformation of adrenocortical cells by K-MSV demonstrates the capacity of this agent to induce carcinomas in differentiated cells after short-term culture, and widens the range of tissues known to be susceptible to K-MSV to include a secretory epithelium of mesodermal origin.", "contents": "Transformation of cultured rat adrenocortical cells by Kirsten murine sarcoma virus (Ki-MSV). Two-week-old primary cultures of normal adult rat adrenal cortex were exposed to Kirsten murine sarcoma virus (KiMSV). Within a week, the adrenal cells, which are normally fusiform and aligned in parallel, became pleomorphic and piled up extensively. Saturation density increased from 5-10 x 10(4) to 5-10 x 10(5) cells/cm2, population doubling time during exponential growth decreased from 36-40 to 16h, acid production increased and the growth rate became independent of a reduction in serum concentration from 10% to 1%. Inoculation of 2 x 10(6) of these transformed cells into immuno-depressed rats produced rapidly growing tumors within 1 week. Histologically, the tumors were pleomorphic carcinomas with areas ranging from anaplasia to near-normal, highly differentiated adrenocortical tissue. In addition to histologic evidence of differentiation, metabolic studies using 14C-prognenolone showed that the transformed cells were capable of 20alpha reduction and delta5,3beta dehydrogenation, both characteristic of normal steroid-secreting tissues. The transformed adrenocortical cells produced infectious C-type virus as indicated by electron microscopy, 3H-uridine incorporation, and focus formation in NRK (normal rat kidney) cultures. The neutralization pattern of this virus resembled that of authentic Ki-MSV. The transformation of adrenocortical cells by K-MSV demonstrates the capacity of this agent to induce carcinomas in differentiated cells after short-term culture, and widens the range of tissues known to be susceptible to K-MSV to include a secretory epithelium of mesodermal origin."}
{"id": "PMID:188773", "title": "Horizontal transmission of feline leukemia virus under natural conditions in a feline leukemia cluster household.", "content": "Ten post-weanling 4-month-old cats, designated \"tracers\", were placed in a feline leukemia cluster household to determine the efficiency of horizontal transmission of feline leukemia virus (FeLV). The tracer cats were confirmed as negative for prior exposure to FeLV. Following the placement in the leukemia cluster environment, the tracer cats were serologically monitored at intervals of 3-6 weeks for a total period of 1 year. The tests employed included the detection of FeLV using fixed-cell immunofluorescence and the detection and titration of antibody to : (1) the feline oncornavirus-associated cell membrane antigen (FOCMA), as detected by membrane immunofluorescence; (2) viable FeLV, using serum neutralization; (3) virion core protein p30, using radioimmunoprecipitation; and (4) virion glycoprotein gp70, using radioimmunoprecipitation. All of the tracers had evidence of horizontal infection by FeLV, by several criteria. Seven of the 10 had virus that could be isolated from plasma. All of these 7 developed a terminal illness within 18 months; 3 developed aplastic anemia, 3 infectious peritonitis, and 1 lymphoma. The remaining 3 were negative for FeLV by both virus isolation and fixed-cell immunofluorescence. These 3 did, however, develop high antibody titers by all four criteria and they remained healthy throughout the examination period. These results clearly indicate that unprotected pros-weanling cats brought into a leukemia exposure household environment have a high risk of becoming infected with FeLV. Furthermore, a large proportion of the cats are at risk for development of persistent viremia and FeLV-related diseases.", "contents": "Horizontal transmission of feline leukemia virus under natural conditions in a feline leukemia cluster household. Ten post-weanling 4-month-old cats, designated \"tracers\", were placed in a feline leukemia cluster household to determine the efficiency of horizontal transmission of feline leukemia virus (FeLV). The tracer cats were confirmed as negative for prior exposure to FeLV. Following the placement in the leukemia cluster environment, the tracer cats were serologically monitored at intervals of 3-6 weeks for a total period of 1 year. The tests employed included the detection of FeLV using fixed-cell immunofluorescence and the detection and titration of antibody to : (1) the feline oncornavirus-associated cell membrane antigen (FOCMA), as detected by membrane immunofluorescence; (2) viable FeLV, using serum neutralization; (3) virion core protein p30, using radioimmunoprecipitation; and (4) virion glycoprotein gp70, using radioimmunoprecipitation. All of the tracers had evidence of horizontal infection by FeLV, by several criteria. Seven of the 10 had virus that could be isolated from plasma. All of these 7 developed a terminal illness within 18 months; 3 developed aplastic anemia, 3 infectious peritonitis, and 1 lymphoma. The remaining 3 were negative for FeLV by both virus isolation and fixed-cell immunofluorescence. These 3 did, however, develop high antibody titers by all four criteria and they remained healthy throughout the examination period. These results clearly indicate that unprotected pros-weanling cats brought into a leukemia exposure household environment have a high risk of becoming infected with FeLV. Furthermore, a large proportion of the cats are at risk for development of persistent viremia and FeLV-related diseases."}
{"id": "PMID:188775", "title": "Treatment approaches to mania.", "content": "Treatment of manic episodes is an urgency because of the lack of insight and excessive psychomotor activity. Over the past two decades various new modes of pharmacological treatment of this condition has been reported. Along with them, biochemical findings in manic patients have been exhaustively investigated. Etiologically based pharmacological treatment of manic episodes will help us therapeutically in improving the condition of the patient and scientifically, to confirm or explore biochemical basis of manic episodes. The new innovative approaches for the treatment of manic episodes need to be applied in treating therapy-resistant patients. Included in this paper are treatment approaches based on norepinephrine, dopamine, acetylcholine, serotonin, gamma-aminobutyric acid and permissive hypothesis, peripheral autonomic imbalance, endocrine abnormalities, electrolyte disturbances, paradoxical response, and cyclic AMP. In addition, use of antidepressants and pyrotherapy is described.", "contents": "Treatment approaches to mania. Treatment of manic episodes is an urgency because of the lack of insight and excessive psychomotor activity. Over the past two decades various new modes of pharmacological treatment of this condition has been reported. Along with them, biochemical findings in manic patients have been exhaustively investigated. Etiologically based pharmacological treatment of manic episodes will help us therapeutically in improving the condition of the patient and scientifically, to confirm or explore biochemical basis of manic episodes. The new innovative approaches for the treatment of manic episodes need to be applied in treating therapy-resistant patients. Included in this paper are treatment approaches based on norepinephrine, dopamine, acetylcholine, serotonin, gamma-aminobutyric acid and permissive hypothesis, peripheral autonomic imbalance, endocrine abnormalities, electrolyte disturbances, paradoxical response, and cyclic AMP. In addition, use of antidepressants and pyrotherapy is described."}
{"id": "PMID:188776", "title": "Prevention by medroxyprogesterone of perforation in the alkali-burned rabbit cornea: inhibition of collagenolytic activity.", "content": "The incidence of perforation and deep ulceration of the alkali-burned rabbit cornea was substantially reduced by topical or parenteral administration of medroxyprogesterone. The mode of action of the hormone is probably at least in part related to its suppressive effects on production of tissue collagenase, as indicated by the considerable reduction in collagenolytic activity by living explants of the treated corneas.", "contents": "Prevention by medroxyprogesterone of perforation in the alkali-burned rabbit cornea: inhibition of collagenolytic activity. The incidence of perforation and deep ulceration of the alkali-burned rabbit cornea was substantially reduced by topical or parenteral administration of medroxyprogesterone. The mode of action of the hormone is probably at least in part related to its suppressive effects on production of tissue collagenase, as indicated by the considerable reduction in collagenolytic activity by living explants of the treated corneas."}
{"id": "PMID:188777", "title": "The ocular anti-inflammatory action of imidazole.", "content": "Imidazole administered intraperitoneally to albino rabbits at a dose of 250 mg. per kilogram inhibited the rise of aqueous humor protein concentration by approximately 50 per cent 30 minutes after paracentesis. Systemic imidazole administered daily to albino rabbits injected with intravitreal Shigella endotoxin decreased the conjunctival and iris hyperemia and reduced the anterior chamber cell and flare and the haziness of the optical media. Systemically administered imidazole had no effect on the aqueous humor concentrations of c-AMP or c-GMP in the rabbit. In vitro studies of rabbit ciliary body-iris phosphodiesterase activity indicated no effect of imidazole at a  concentration of 10(-3) molar.", "contents": "The ocular anti-inflammatory action of imidazole. Imidazole administered intraperitoneally to albino rabbits at a dose of 250 mg. per kilogram inhibited the rise of aqueous humor protein concentration by approximately 50 per cent 30 minutes after paracentesis. Systemic imidazole administered daily to albino rabbits injected with intravitreal Shigella endotoxin decreased the conjunctival and iris hyperemia and reduced the anterior chamber cell and flare and the haziness of the optical media. Systemically administered imidazole had no effect on the aqueous humor concentrations of c-AMP or c-GMP in the rabbit. In vitro studies of rabbit ciliary body-iris phosphodiesterase activity indicated no effect of imidazole at a  concentration of 10(-3) molar."}
{"id": "PMID:188778", "title": "The corneal response to Pseudomonas aeruginosa: histopathological and enzymatic characterization.", "content": "The host response to the intrastromal injection of heat-inactivated Pseudomonas aeruginosa cells was studied. An extensive polymorphonuclear leukocyte (PMN) infiltration, which progressed to ulceration within 1 week, was observed. In some cases descemetoceles also developed. Only a limited degree of PMN infiltration and no ulcerations were observed at 1 week in eyes treated with corticosteroids. Collagenase and proteolytic enzymes capable of degrading proteoglycans were found in the ulcerated corneas. A correlation was made between the level of these host-derived enzymes and the extent of corneal destruction. It was concluded that corneal destruction by P. aeruginosa depends not only on the Pseudomonas protease, which rapidly destroys the cornea, but also on host-derived enzymes which are capable of degrading both collagen and proteoglycans.", "contents": "The corneal response to Pseudomonas aeruginosa: histopathological and enzymatic characterization. The host response to the intrastromal injection of heat-inactivated Pseudomonas aeruginosa cells was studied. An extensive polymorphonuclear leukocyte (PMN) infiltration, which progressed to ulceration within 1 week, was observed. In some cases descemetoceles also developed. Only a limited degree of PMN infiltration and no ulcerations were observed at 1 week in eyes treated with corticosteroids. Collagenase and proteolytic enzymes capable of degrading proteoglycans were found in the ulcerated corneas. A correlation was made between the level of these host-derived enzymes and the extent of corneal destruction. It was concluded that corneal destruction by P. aeruginosa depends not only on the Pseudomonas protease, which rapidly destroys the cornea, but also on host-derived enzymes which are capable of degrading both collagen and proteoglycans."}
{"id": "PMID:188779", "title": "Localization of cyclic nucleotide phosphodiesterase activity within the bovine photoreceptor cell.", "content": "Cyclic nucleotide phosphodiesterase was measured in the outer layers of the bovine retina by quantitative histochemical methods. The outer segment region contained the highest specific enzyme activity. Phosphodiesterase activity with different kinetic properties was also observed in the outer plexiform layer.", "contents": "Localization of cyclic nucleotide phosphodiesterase activity within the bovine photoreceptor cell. Cyclic nucleotide phosphodiesterase was measured in the outer layers of the bovine retina by quantitative histochemical methods. The outer segment region contained the highest specific enzyme activity. Phosphodiesterase activity with different kinetic properties was also observed in the outer plexiform layer."}
{"id": "PMID:188774", "title": "\"Planned\" management of squamous cell carcinoma of the mandibular oropharynx.", "content": "The term \"planned,\" where management of squamous cell carcinoma of the mandibular oropharynx is concerned, has been put into proper perspective with several case examples in order to clarify its relationship to the pathophysiology of the disease and the anticipated morbidity involved in its cure.", "contents": "\"Planned\" management of squamous cell carcinoma of the mandibular oropharynx. The term \"planned,\" where management of squamous cell carcinoma of the mandibular oropharynx is concerned, has been put into proper perspective with several case examples in order to clarify its relationship to the pathophysiology of the disease and the anticipated morbidity involved in its cure."}
{"id": "PMID:188780", "title": "Growth characteristics of acute hemorrhagic conjunctivitis (AHC) virus in monkey kidney cells. II. Temperature sensitivity of the isolates obtained at various epidemic areas.", "content": "Acute hemorrhagic conjunctivitis (AHC) virus strains isolated in eight different areas during epidemics of AHC were tested for the reproductive capacity at 33, 37 and 39 degrees. All of the 25 strains tested grew better at 33 degrees but restrictively at 39 degrees. The degree of temperature sensitivity varied slightly from one strain to the other, but generally exceeded that of attenuated poliovirus type 1, strain LSc2ab. Temperature-resistant clones were selected by repeated passages of originally temperature-sensitive prototype strains at supraoptimal temperature. The importance of using a low temperature (32-34 degrees) for isolation of virus from external tissues of the body and for subsequent passages has been emphasized. It was suggested that the relatively low temperature of the conjunctiva has played a role in perpetuating temperature sensitivity of this virus.", "contents": "Growth characteristics of acute hemorrhagic conjunctivitis (AHC) virus in monkey kidney cells. II. Temperature sensitivity of the isolates obtained at various epidemic areas. Acute hemorrhagic conjunctivitis (AHC) virus strains isolated in eight different areas during epidemics of AHC were tested for the reproductive capacity at 33, 37 and 39 degrees. All of the 25 strains tested grew better at 33 degrees but restrictively at 39 degrees. The degree of temperature sensitivity varied slightly from one strain to the other, but generally exceeded that of attenuated poliovirus type 1, strain LSc2ab. Temperature-resistant clones were selected by repeated passages of originally temperature-sensitive prototype strains at supraoptimal temperature. The importance of using a low temperature (32-34 degrees) for isolation of virus from external tissues of the body and for subsequent passages has been emphasized. It was suggested that the relatively low temperature of the conjunctiva has played a role in perpetuating temperature sensitivity of this virus."}
{"id": "PMID:188781", "title": "The oncornavirus maturation process: quantitative correlation between morphological changes and conversion of genomic virion RNA.", "content": "Avian myeloblastosis virus (AMV) was harvested at different time intervals from chick leukemic myeloblasts, and the rate of the maturation process of AMV was estimated on the basis of morphological changes in the virions and conversion of genomic viral RNA. The change from immature virions characterized by the presence of an electronlucent center to the condensed mature form (with dense nucleoid) was accompanied by the conversion of 30-40S RNA to 60S RNA. Both processes were quantitatively defined, correlated, and found to proceed in parallel at the same speed. Early stages of maturation were characterized by a high turnover of immature to mature virions; 31-40% of the mature forms were found in 3.5-min virus harvests. The rate of this process decreased with time. The 17-hour harvests still revealed the presence of 10-15% of immature virions. The course of the maturation process is discussed.", "contents": "The oncornavirus maturation process: quantitative correlation between morphological changes and conversion of genomic virion RNA. Avian myeloblastosis virus (AMV) was harvested at different time intervals from chick leukemic myeloblasts, and the rate of the maturation process of AMV was estimated on the basis of morphological changes in the virions and conversion of genomic viral RNA. The change from immature virions characterized by the presence of an electronlucent center to the condensed mature form (with dense nucleoid) was accompanied by the conversion of 30-40S RNA to 60S RNA. Both processes were quantitatively defined, correlated, and found to proceed in parallel at the same speed. Early stages of maturation were characterized by a high turnover of immature to mature virions; 31-40% of the mature forms were found in 3.5-min virus harvests. The rate of this process decreased with time. The 17-hour harvests still revealed the presence of 10-15% of immature virions. The course of the maturation process is discussed."}
{"id": "PMID:188782", "title": "DNA-binding proteins of cells infected by herpes simplex virus type 1 and type 2.", "content": "Proteins showing affinity for DNA in HSV-1-and HSV-2-infected cells were compared by DNA-cellulose chromatography and PAGE. The proteins observed depended on the type of virus used to infect the cell; however, several examples of analogous polypeptides were present in cells infected by both virus types. Proteins showing highest affinity for DNA-cellulose were similar in molecular size in cells infected by both virus types.", "contents": "DNA-binding proteins of cells infected by herpes simplex virus type 1 and type 2. Proteins showing affinity for DNA in HSV-1-and HSV-2-infected cells were compared by DNA-cellulose chromatography and PAGE. The proteins observed depended on the type of virus used to infect the cell; however, several examples of analogous polypeptides were present in cells infected by both virus types. Proteins showing highest affinity for DNA-cellulose were similar in molecular size in cells infected by both virus types."}
{"id": "PMID:188783", "title": "An ultrastructural study and model of membrane-intramitochondrial virus relationships.", "content": "Intramitochondrial virions (IMV), in many respects structurally similar to 'C-type' viruses of higher organisms, are synthesized in close topographical association with inner mitochondrial membranes of the viper spleen cell line, VSW. Cristal membranes contribute to the formation of a trilaminar viral envelope, whereas the outer mitochondrial membrane does not appear to play any structural role in virion maturation. Two schematic models, correlated with electron microscopic images, are presented to depict: (a) the relative location of the particles within a three-dimensional view of the mitochondrion, and (b) the sequence of virion-mitochondrial membrane relationships during morphogenesis.", "contents": "An ultrastructural study and model of membrane-intramitochondrial virus relationships. Intramitochondrial virions (IMV), in many respects structurally similar to 'C-type' viruses of higher organisms, are synthesized in close topographical association with inner mitochondrial membranes of the viper spleen cell line, VSW. Cristal membranes contribute to the formation of a trilaminar viral envelope, whereas the outer mitochondrial membrane does not appear to play any structural role in virion maturation. Two schematic models, correlated with electron microscopic images, are presented to depict: (a) the relative location of the particles within a three-dimensional view of the mitochondrion, and (b) the sequence of virion-mitochondrial membrane relationships during morphogenesis."}
{"id": "PMID:188788", "title": "[Clinical diagnosis of frequent skin tumors].", "content": "Some clinical differential diagnostic aspects of frequent or otherwise important skin tumors and precancerous lesions, grouped after their gross nodular or ulcerated, papillomatous or flat appearances, are compiled.", "contents": "[Clinical diagnosis of frequent skin tumors]. Some clinical differential diagnostic aspects of frequent or otherwise important skin tumors and precancerous lesions, grouped after their gross nodular or ulcerated, papillomatous or flat appearances, are compiled."}
{"id": "PMID:188789", "title": "Laboratory confirmation of an outbreak of Clostridium perfringens food poisoning.", "content": "A foodborne outbreak in a group of eleven individuals sharing a common meal, eight of whom reported symptoms and an incubation period compatible with Clostridium perfringens food poisoning, was confirmed by the following laboratory criteria: (a) the C. perfringens count in the suspect food, chicken pie, was at least 10(5) per gram; (b) the median fecal C. perfringens spore count in convalescing patients was greater than 10(6) per gram: (c) an indentical serotype (PS63) was isolated from both the food and fecal specimens; and (d) the C. perfringens isolates from most of the patients (8 out of 10) were of the same serotype. The results confirm the usefulness of fecal spore counts and serotyping in implicating C perfringens in food poisoning outbreaks.", "contents": "Laboratory confirmation of an outbreak of Clostridium perfringens food poisoning. A foodborne outbreak in a group of eleven individuals sharing a common meal, eight of whom reported symptoms and an incubation period compatible with Clostridium perfringens food poisoning, was confirmed by the following laboratory criteria: (a) the C. perfringens count in the suspect food, chicken pie, was at least 10(5) per gram; (b) the median fecal C. perfringens spore count in convalescing patients was greater than 10(6) per gram: (c) an indentical serotype (PS63) was isolated from both the food and fecal specimens; and (d) the C. perfringens isolates from most of the patients (8 out of 10) were of the same serotype. The results confirm the usefulness of fecal spore counts and serotyping in implicating C perfringens in food poisoning outbreaks."}
{"id": "PMID:188792", "title": "Pathology of experimentally induced polybrominated biphenyl toxicosis in pregnant heifers.", "content": "Toxicosis was induced in pregnant Holstein-Friesian heifers by giving polybrominated biphenyls a in gelatin capsules at the rate of 25 g/day. Initially, this dosage was approximately 67 mg/kg of body weight. Clinical signs were anorexia, excessive lacrimation and salivation, diarrhea, emaciation, dehydration, depression, and abortion. Fever was not evident during the experiment. Values for serum glutamic-oxalacetic transaminase, lactic dehydrogenase, blood urea nitrogen, and bilirubin were increased. Changes in packed cell volume, hemoglobin content, total erythrocyte and leukocyte counts, and differential leukocyte counts were minimal and reflected dehydration and secondary infection. The principal urine changes were decreased specific gravity and moderate proteinuria. Gross necropsy findings included dehydration; subcutaneous emphysema and hemorrhage; atrophy of the thymus; fetal death with concomitant necrosis of cotyledons; kidneys that were enlarged, pale tan to gray; thickened wall of the gallbladder; inspissated bile; edema of abomasal folds; mucoid enteritis; linear hemorrhage and edema of the rectal mucosa; and secondary pneumonia. Microscopic changes were most marked in the kidneys, gallbladder, and eyelid. In the kidney, the principal changes were extreme dilatation of collecting ducts and convoluted tubules, with epithelial degenerative changes of cloudy swelling, hydropic degeneration, and separation from the basement membrane. Common changes in the gallbladder were moderate to marked hyperplasia and cystic dilatation of the mucous glands in the lamina propria. The changes in the eyelids were characterized by hyperkeratosis, with accumulations of keratin in hair follicles of the epidermis and squamous metaplasia with keratin cysts in the tarsal glands. Clinical signs and lesions of toxicosis did not develop in heifers given the polybrominated biphenyls at the rate of 0.25 mg and 250 mg/day for 60 days. Initially these rates were approximately 0.00065 mg/kg and 0.65 mg/kg of body weight, respectively.", "contents": "Pathology of experimentally induced polybrominated biphenyl toxicosis in pregnant heifers. Toxicosis was induced in pregnant Holstein-Friesian heifers by giving polybrominated biphenyls a in gelatin capsules at the rate of 25 g/day. Initially, this dosage was approximately 67 mg/kg of body weight. Clinical signs were anorexia, excessive lacrimation and salivation, diarrhea, emaciation, dehydration, depression, and abortion. Fever was not evident during the experiment. Values for serum glutamic-oxalacetic transaminase, lactic dehydrogenase, blood urea nitrogen, and bilirubin were increased. Changes in packed cell volume, hemoglobin content, total erythrocyte and leukocyte counts, and differential leukocyte counts were minimal and reflected dehydration and secondary infection. The principal urine changes were decreased specific gravity and moderate proteinuria. Gross necropsy findings included dehydration; subcutaneous emphysema and hemorrhage; atrophy of the thymus; fetal death with concomitant necrosis of cotyledons; kidneys that were enlarged, pale tan to gray; thickened wall of the gallbladder; inspissated bile; edema of abomasal folds; mucoid enteritis; linear hemorrhage and edema of the rectal mucosa; and secondary pneumonia. Microscopic changes were most marked in the kidneys, gallbladder, and eyelid. In the kidney, the principal changes were extreme dilatation of collecting ducts and convoluted tubules, with epithelial degenerative changes of cloudy swelling, hydropic degeneration, and separation from the basement membrane. Common changes in the gallbladder were moderate to marked hyperplasia and cystic dilatation of the mucous glands in the lamina propria. The changes in the eyelids were characterized by hyperkeratosis, with accumulations of keratin in hair follicles of the epidermis and squamous metaplasia with keratin cysts in the tarsal glands. Clinical signs and lesions of toxicosis did not develop in heifers given the polybrominated biphenyls at the rate of 0.25 mg and 250 mg/day for 60 days. Initially these rates were approximately 0.00065 mg/kg and 0.65 mg/kg of body weight, respectively."}
{"id": "PMID:188794", "title": "Histochemical observations on chicken blood and bone marrow cells.", "content": "The distribution of lipid, glycogen, peroxidase, alkaline phosphatase and acid phosphatase has been studied in the cells of blood and bone marrow smears from young chickens. Chicken heterophil granules react differently from those of mammalian neutrophils. A strongly positive peroxidase reaction was given by developing erythrocytes in chickens, unlike mammals. The significance of these species differences is not yet clear.", "contents": "Histochemical observations on chicken blood and bone marrow cells. The distribution of lipid, glycogen, peroxidase, alkaline phosphatase and acid phosphatase has been studied in the cells of blood and bone marrow smears from young chickens. Chicken heterophil granules react differently from those of mammalian neutrophils. A strongly positive peroxidase reaction was given by developing erythrocytes in chickens, unlike mammals. The significance of these species differences is not yet clear."}
{"id": "PMID:188795", "title": "Mode of action of bredinin with guanylic acid on L5178Y mouse leukemia cells.", "content": "Moderate concentrations of bredinin (1.2 X 10(-5) M) strongly inhibited growth of L5178Y cells, with the effect being reversed by guanylic acid (GMP). However, at higher concentrations of breeding the inhibition was not reversed completely by GMP added in excess. Bredinin was cytocidal at concentrations above 2 X 10(-5) M, but 5 X 10(-5) M bredinin in the presence of excess GMP, bredinin was cytostatic. Bredinin inhibited nucleic acid synthesis of L5178Y cells, but bredinin itself was not incorporated into the nucleic acid. Inhibition of nucleic acid synthesis was clearly reversed by GMP. Similarly chromosomal aberrations in L5178Y cells caused by bredinin were reversed by GMP. In contrast, the effect of ahigh concentration of bredinin on cell multiplication was not reversed by GMP. The modal volume of L5178Y cells increased during incubation in the presence of bredinin and GMP for 24 hours, 5 X 10(-5) M bredinin with GMP causing a 70% increase in cell volume. This increase in cell volume was mainly due to an increase in the protein content of the cells. The cytostatic effect of bredinin with GMP was reversed completely by adenosine-3',5'-cyclic monophosphate (cyclic AMP). Other cyclic nucleotides and nucleotides were ineffective. The reversing effect of cyclic AMP on cell survival depended upon the concentration of GMP, and was not seen in the absence of GMP. It was concluded that cyclic AMP influences the secondary cytostatic effect of bredinin, and not the primary cytotoxic effect reversed by GMP.", "contents": "Mode of action of bredinin with guanylic acid on L5178Y mouse leukemia cells. Moderate concentrations of bredinin (1.2 X 10(-5) M) strongly inhibited growth of L5178Y cells, with the effect being reversed by guanylic acid (GMP). However, at higher concentrations of breeding the inhibition was not reversed completely by GMP added in excess. Bredinin was cytocidal at concentrations above 2 X 10(-5) M, but 5 X 10(-5) M bredinin in the presence of excess GMP, bredinin was cytostatic. Bredinin inhibited nucleic acid synthesis of L5178Y cells, but bredinin itself was not incorporated into the nucleic acid. Inhibition of nucleic acid synthesis was clearly reversed by GMP. Similarly chromosomal aberrations in L5178Y cells caused by bredinin were reversed by GMP. In contrast, the effect of ahigh concentration of bredinin on cell multiplication was not reversed by GMP. The modal volume of L5178Y cells increased during incubation in the presence of bredinin and GMP for 24 hours, 5 X 10(-5) M bredinin with GMP causing a 70% increase in cell volume. This increase in cell volume was mainly due to an increase in the protein content of the cells. The cytostatic effect of bredinin with GMP was reversed completely by adenosine-3',5'-cyclic monophosphate (cyclic AMP). Other cyclic nucleotides and nucleotides were ineffective. The reversing effect of cyclic AMP on cell survival depended upon the concentration of GMP, and was not seen in the absence of GMP. It was concluded that cyclic AMP influences the secondary cytostatic effect of bredinin, and not the primary cytotoxic effect reversed by GMP."}
{"id": "PMID:188791", "title": "Corticotroph cells in primary cultures of rat adenohypophysis: a light and electron microscopic immunocytochemical study.", "content": "Monolayer cultures of trypsin-dispersed cells of the rat adenohypophysis were grown for 5 to 54 days. ACTH was localized by immunocytochemistry using an antiserum to synthetic ACTH1-28 prepared in rabbit and sheep anti-goat immunoglobulin coupled with peroxidase. ACTH content of the culture medium was measured by radioimmunoassay. Corttion time. The corticotrophs retained their essential morphological characteristics. Immunological staining was found in the secretory granules, some tubular or saccular structures, parts of the rough endoplasmic reticulum, and the cytoplasmic matrix. Immature secretory granules in the Golgi apparatus as well as some Golgi elements showed different degrees of immunoreactivity. In agreement with the high ACTH content of the culture medium the number, size and shape of the secretory granules, the active Golgi apparatus, the high amount of extragranular ACTH as well as pictures suggesting granule extrusion claim for a high ACTH synthesis and transport (and low ACTH storage) in the cultured corticotrophs.", "contents": "Corticotroph cells in primary cultures of rat adenohypophysis: a light and electron microscopic immunocytochemical study. Monolayer cultures of trypsin-dispersed cells of the rat adenohypophysis were grown for 5 to 54 days. ACTH was localized by immunocytochemistry using an antiserum to synthetic ACTH1-28 prepared in rabbit and sheep anti-goat immunoglobulin coupled with peroxidase. ACTH content of the culture medium was measured by radioimmunoassay. Corttion time. The corticotrophs retained their essential morphological characteristics. Immunological staining was found in the secretory granules, some tubular or saccular structures, parts of the rough endoplasmic reticulum, and the cytoplasmic matrix. Immature secretory granules in the Golgi apparatus as well as some Golgi elements showed different degrees of immunoreactivity. In agreement with the high ACTH content of the culture medium the number, size and shape of the secretory granules, the active Golgi apparatus, the high amount of extragranular ACTH as well as pictures suggesting granule extrusion claim for a high ACTH synthesis and transport (and low ACTH storage) in the cultured corticotrophs."}
{"id": "PMID:188799", "title": "Variations in evaporation and body temperatures during sleep in man.", "content": "The thermal balance in man was investigated during nocturnal sleep in neutral and warm environments (from 32 to 39.5 degrees C, 45%rh). Changes of body temperatures and skin evaporation were continuously monitored throughout the whole night. In neutral conditions (32 and 34 degrees C) body temperature and skin evaporation decreased during the night, following the circadian rhythm deltaT sk = -0.34 degrees C; deltaT re = -0.52 degrees C;deltaE = -12 W-m-2. In warm conditions, body temperatures and evaporation remained steady. Marked fluctuations of body temperatures and evaporation occurred synchronously with the rapid eye movement (REM) periods. Each REM period induced phasic increase of Tsk reaching +2 degrees C in some cases, with a cessation of evaporation. Tre showed upward and downward rhythmical waves synchronously with REM sleep occurrence. The nocturnal variations of thermal balance were characterized by two rhythms: a basal circadian rhythm and superimposed on it a rhythm conditioned by occurrence of REM sleep every 80-90 min. The phasic changes of body temperatures and evaporation only appeared with REM's. The results suggest that the nervous integrative function conditioning the patterns of sleep, conditions also the phasic cyclic changes of thermoregulatory function.", "contents": "Variations in evaporation and body temperatures during sleep in man. The thermal balance in man was investigated during nocturnal sleep in neutral and warm environments (from 32 to 39.5 degrees C, 45%rh). Changes of body temperatures and skin evaporation were continuously monitored throughout the whole night. In neutral conditions (32 and 34 degrees C) body temperature and skin evaporation decreased during the night, following the circadian rhythm deltaT sk = -0.34 degrees C; deltaT re = -0.52 degrees C;deltaE = -12 W-m-2. In warm conditions, body temperatures and evaporation remained steady. Marked fluctuations of body temperatures and evaporation occurred synchronously with the rapid eye movement (REM) periods. Each REM period induced phasic increase of Tsk reaching +2 degrees C in some cases, with a cessation of evaporation. Tre showed upward and downward rhythmical waves synchronously with REM sleep occurrence. The nocturnal variations of thermal balance were characterized by two rhythms: a basal circadian rhythm and superimposed on it a rhythm conditioned by occurrence of REM sleep every 80-90 min. The phasic changes of body temperatures and evaporation only appeared with REM's. The results suggest that the nervous integrative function conditioning the patterns of sleep, conditions also the phasic cyclic changes of thermoregulatory function."}
{"id": "PMID:188800", "title": "Influence of fasting on the lung.", "content": "We examined the following in fed rats and in rats fasted for 72 h: 1) the dipalmitoyl lecithin (DPL) content of lung lavage fluid and of the remaining lung tissue, 2) descending air and saline pressure-volume curves of excised lungs, and 3) the volume density of granular pneumocyte lamellar bodies. Lung tissue DPL was decreased by 27% and lavage DPL was decreased by 40% in lungs of fasted rats. The decreased lung DPL content was associated with a 20% decrease in the volume density of lamellar bodies of granular pneumocytes. In spite of the decrease in lavage DPL content, air pressure-volume curves of excised lungs were the same as curves of lungs of fed rats. Saline pressure-volume curves of excised lungs were also the same in fed and fasted rats. The amount of lavage DPL obtained from both fed (1.1 +/- 0.1 mg, n=6) and fasted (0.7 +/- 0.1 mg, n=7) rats exceeded the theoretical minimum amount of DPL (0.5 mg) required for a monomolecular film to cover the alveolar surface of the rat at functional residual capacity. If we assume that lavage DPL represents mainly DPL lining the alveolus (surface film and hypophase) the data suggest that there is an alveolar reserve of DPL above that amount needed to maintain normal alveolar stability.", "contents": "Influence of fasting on the lung. We examined the following in fed rats and in rats fasted for 72 h: 1) the dipalmitoyl lecithin (DPL) content of lung lavage fluid and of the remaining lung tissue, 2) descending air and saline pressure-volume curves of excised lungs, and 3) the volume density of granular pneumocyte lamellar bodies. Lung tissue DPL was decreased by 27% and lavage DPL was decreased by 40% in lungs of fasted rats. The decreased lung DPL content was associated with a 20% decrease in the volume density of lamellar bodies of granular pneumocytes. In spite of the decrease in lavage DPL content, air pressure-volume curves of excised lungs were the same as curves of lungs of fed rats. Saline pressure-volume curves of excised lungs were also the same in fed and fasted rats. The amount of lavage DPL obtained from both fed (1.1 +/- 0.1 mg, n=6) and fasted (0.7 +/- 0.1 mg, n=7) rats exceeded the theoretical minimum amount of DPL (0.5 mg) required for a monomolecular film to cover the alveolar surface of the rat at functional residual capacity. If we assume that lavage DPL represents mainly DPL lining the alveolus (surface film and hypophase) the data suggest that there is an alveolar reserve of DPL above that amount needed to maintain normal alveolar stability."}
{"id": "PMID:188801", "title": "Chelate extraction and flame atomic absorption spectrometric determination of nanogram amounts of manganese in blood and animal tissue.", "content": "A method for the determination of manganese in blood and animal tissue has been developed involving wet digestion of the sample by perchloric and nitric acids, complexing with sodium diethyldithiocarbamate, and extracting with methyl isobutyl ketone at pH 6.7. The methyl isobutyl ketone is removed, and the residue is dissolved in 0.05N HCl in acetone-water (9 + 1) and is aspirated into an air-acetylene flame of an atomic absorption spectrometer. The limit of detectability is about 10 ng Mn/ml in the solution aspirated or 2 ng Mn/ml in bovine blood for a 20 ml sample.", "contents": "Chelate extraction and flame atomic absorption spectrometric determination of nanogram amounts of manganese in blood and animal tissue. A method for the determination of manganese in blood and animal tissue has been developed involving wet digestion of the sample by perchloric and nitric acids, complexing with sodium diethyldithiocarbamate, and extracting with methyl isobutyl ketone at pH 6.7. The methyl isobutyl ketone is removed, and the residue is dissolved in 0.05N HCl in acetone-water (9 + 1) and is aspirated into an air-acetylene flame of an atomic absorption spectrometer. The limit of detectability is about 10 ng Mn/ml in the solution aspirated or 2 ng Mn/ml in bovine blood for a 20 ml sample."}
{"id": "PMID:188802", "title": "Effect of guanosine 3' : 5'-monophosphate on glucose oxidation and epinephrine-stimulated lipolysis in isolated rat epididymal fat cells.", "content": "The guanosine 3': 5'-monophosphate (cyclic GMP) level in isolated rat epididymal fat cells increased more than doubled 10 min after addition to the cells of carbamylcholine (10(-6) M) in the presence or absence of epinephrine (5 X 10(-7) M). Addition of carbamylcholine, cyclic GMP or dibutyryl cyclic GMP (10(-9) to 10(-5) M) did not affect glucose oxidation or epinephrine-stimulated lipolysis of the cells. No significant change in the cyclic GMP level was detected 2 min or 10 min after addition of insulin (1 mU/ml) to the cells, when glucose oxidation was stimulated and lipolysis induced by epinephrine was inhibited. These results indicate that the transient increase in the cyclic GMP level in the cells on treatment with carbamylcholine is not sufficient for expression of the effects of insulin.", "contents": "Effect of guanosine 3' : 5'-monophosphate on glucose oxidation and epinephrine-stimulated lipolysis in isolated rat epididymal fat cells. The guanosine 3': 5'-monophosphate (cyclic GMP) level in isolated rat epididymal fat cells increased more than doubled 10 min after addition to the cells of carbamylcholine (10(-6) M) in the presence or absence of epinephrine (5 X 10(-7) M). Addition of carbamylcholine, cyclic GMP or dibutyryl cyclic GMP (10(-9) to 10(-5) M) did not affect glucose oxidation or epinephrine-stimulated lipolysis of the cells. No significant change in the cyclic GMP level was detected 2 min or 10 min after addition of insulin (1 mU/ml) to the cells, when glucose oxidation was stimulated and lipolysis induced by epinephrine was inhibited. These results indicate that the transient increase in the cyclic GMP level in the cells on treatment with carbamylcholine is not sufficient for expression of the effects of insulin."}
{"id": "PMID:188803", "title": "High affinity binders for cyclic adenosine 3', 5'-monophosphate on plasma membranes isolated from rat liver and ascites hepatomas.", "content": "Plasma membranes from rat liver were found to contain at least two types of specific binding sites for cyclic [3H] adenosine 3', 5'-monophosphate (c[3H]AMP) with apparent dissociation constants of 0.51 +/- 0.14 and 2.9 +/- 0.6 nM (O degrees), respectively. The levels of these binding sites in liver plasma membranes were about 0.60 +/- 0.20 and 1.3 +/- 0.5 pmole/mg protein. The highest affinity binders for c[3H]AMP were found to be reduced in amount in plasma membranes of ascites hepatomas to 1/3 to 1/4 as compared with liver membranes in the cases of AH-130 and AH-7974 and to an almost undetectable level in the case of AH-130F(N). No difference in the endogenous phosphorylation of plasma membranes by (gamma-32P])ATP was, however, detected among liver and hepatoma plasma membranes. Addition of cAMP or cGMP at various concentrations did not affect the endogenous phosphorylation of plasma membranes of these cells.", "contents": "High affinity binders for cyclic adenosine 3', 5'-monophosphate on plasma membranes isolated from rat liver and ascites hepatomas. Plasma membranes from rat liver were found to contain at least two types of specific binding sites for cyclic [3H] adenosine 3', 5'-monophosphate (c[3H]AMP) with apparent dissociation constants of 0.51 +/- 0.14 and 2.9 +/- 0.6 nM (O degrees), respectively. The levels of these binding sites in liver plasma membranes were about 0.60 +/- 0.20 and 1.3 +/- 0.5 pmole/mg protein. The highest affinity binders for c[3H]AMP were found to be reduced in amount in plasma membranes of ascites hepatomas to 1/3 to 1/4 as compared with liver membranes in the cases of AH-130 and AH-7974 and to an almost undetectable level in the case of AH-130F(N). No difference in the endogenous phosphorylation of plasma membranes by (gamma-32P])ATP was, however, detected among liver and hepatoma plasma membranes. Addition of cAMP or cGMP at various concentrations did not affect the endogenous phosphorylation of plasma membranes of these cells."}
{"id": "PMID:188804", "title": "Phosphorylation of rabbit and human erythrocyte membranes by soluble adenosine 3':5'-monophosphate-dependent and -independent protein kinases.", "content": "Previous reports from this laboratory and others have established that both the rabbit and human erythrocyte membranes contain multiple protein kinase and phosphate acceptor activities. We now report that these membranes also contain phosphoryl acceptor sites for the soluble cyclic AMP-dependent and -independent protein kinases from rabbit erythrocytes. The rabbit erythrocyte membrane, which does not contain a cyclic AMP-dependent protein kinase, has at least four polypeptides (Bands 2.1, 2.3, 4.5, and 4.8) which are phosphorylated in the presence of the soluble cyclic AMP-dependent protein kinases I, IIa, and IIb isolated from rabbit erythrocyte lysates. The resulting phosphoprotein profile is very similar to that obtained for the cyclic AMP-mediated autophosphorylation of human erythrocyte membranes. The activities of the soluble cyclic AMP-dependent protein kinases toward the membranes have been studied at several pH values. Although the substrate specificity of the three kinases is similar, polypeptide 2.3 appears to be phosphorylated to a greater extent by kinase IIa than by I or IIb. This occurs at all pH values  studied. Also apparent is that the pH profile for membrane phosphorylation is different from that of histone phosphorylation. The phosphorylation of membrane proteins can also be catalyzed by the soluble erythrocyte casein kinases. These enzymes are not regulated by cyclic nucleotides and can use either ATP or GTP as their phosphoryl donor. Polypeptides 2.1, 2.9, 4.1, 4.5, 4.8, and 5 of both human and rabbit erythrocyte membranes are phosphorylated in the presence of GTP and the casein kinases. This reaction is optimal at pH 7.5. Experiments were performed to determine whether the phosphorylation of the membranes by the soluble and membrane-bound kinases is additive or exclusive. Our results indicate that after maximal autophosphorylation of the erythrocyte membranes, phosphoryl acceptor sites are available to the soluble cyclic AMP-dependent and -independent protein kinases. Furthermore, after maximal phosphorylation of the membranes with one type of soluble kinase, further 32P incorporation can occur as a result of exposure to the other type of soluble kinase.", "contents": "Phosphorylation of rabbit and human erythrocyte membranes by soluble adenosine 3':5'-monophosphate-dependent and -independent protein kinases. Previous reports from this laboratory and others have established that both the rabbit and human erythrocyte membranes contain multiple protein kinase and phosphate acceptor activities. We now report that these membranes also contain phosphoryl acceptor sites for the soluble cyclic AMP-dependent and -independent protein kinases from rabbit erythrocytes. The rabbit erythrocyte membrane, which does not contain a cyclic AMP-dependent protein kinase, has at least four polypeptides (Bands 2.1, 2.3, 4.5, and 4.8) which are phosphorylated in the presence of the soluble cyclic AMP-dependent protein kinases I, IIa, and IIb isolated from rabbit erythrocyte lysates. The resulting phosphoprotein profile is very similar to that obtained for the cyclic AMP-mediated autophosphorylation of human erythrocyte membranes. The activities of the soluble cyclic AMP-dependent protein kinases toward the membranes have been studied at several pH values. Although the substrate specificity of the three kinases is similar, polypeptide 2.3 appears to be phosphorylated to a greater extent by kinase IIa than by I or IIb. This occurs at all pH values  studied. Also apparent is that the pH profile for membrane phosphorylation is different from that of histone phosphorylation. The phosphorylation of membrane proteins can also be catalyzed by the soluble erythrocyte casein kinases. These enzymes are not regulated by cyclic nucleotides and can use either ATP or GTP as their phosphoryl donor. Polypeptides 2.1, 2.9, 4.1, 4.5, 4.8, and 5 of both human and rabbit erythrocyte membranes are phosphorylated in the presence of GTP and the casein kinases. This reaction is optimal at pH 7.5. Experiments were performed to determine whether the phosphorylation of the membranes by the soluble and membrane-bound kinases is additive or exclusive. Our results indicate that after maximal autophosphorylation of the erythrocyte membranes, phosphoryl acceptor sites are available to the soluble cyclic AMP-dependent and -independent protein kinases. Furthermore, after maximal phosphorylation of the membranes with one type of soluble kinase, further 32P incorporation can occur as a result of exposure to the other type of soluble kinase."}
{"id": "PMID:188806", "title": "Significance of multiple forms of brain monoamine oxidase in situ as probed by electron spin resonance.", "content": "Spin-labeled hydroxyamphetamine, a competitive reversible inhibitor of brain monoamine oxidase, has been shown to be useful as an electron spin resonance (ESR) probe of the microenvironment of the active sites of the possible monoamine oxidase multiple forms. The ESR spectrum of spin-labeled hydroxyamphetamine was strongly quenched upon binding to the enzyme. The conformation of the active site of rat brain monoamine oxidase existing in various physical states, i.e. monoamine oxidase in situ (intact brain mitochondria), crude solubilized monoamine oxidase (MAOS) and isolated monoamine oxidase fractions (MAOa and MAOb) were critically and systematically examined. Nonlinear least squares regression analyses have been used to fit the binding data (obtained at room temperature with varying spin-labeled hydroxyamphetamine concentrations) to three groups of independent noninteracting ligand-binding models. A Gibbs-Helmholtz relationship was applied to the interpretation of the measured apparent association constant K as a function of temperature ranging from 4-50 degrees with increments of 2 degreesmfrom the extracted intensive parameters, k (intrinsic association constant) and deltaF (intrinsic free energy), as well as the apparent heat, deltaH, it was clear that the microenvironment of the binding sites existing in the more purified enzyme fractions MAOa and MAOb were similar to those found in the crude solubilized enzyme. More importantly, they correlated well with the conformation of the sites characterized in situ. The data suggested that the microenvironment of this multienzyme system was unperturbed in spite of the treatment due to the isolation process. In terms of the composition of binding sites, MAOa appeared to be heterogeneous while MAOb appeared to be more homogeneous. Since the isolated fractions MAOa and MAOb possessed marked different substrate specificities, these observations directly implied that monoamine oxidase multiple forms do exist in situ. The extracted extensive parameters, n (specific binding activity, nanomoles/mg of protein), as well as the measured characteristic transition temperatures, indicated that the relative abundance of the sites which directly affected substrate specificities was indeed altered. The consistency of the characteristic transition temperatures of 21 degrees and 38 degrees for the case of intact membrane preparations was particularly significant. A tenable hypothesis is that the manipulation in the composition of the monoamine oxidase binding forms through intimate lipid-protein interactions, which has been amply demonstrated in many biomembrane systems to be functionally important might be the underlying regulatory mechanism in vivo.", "contents": "Significance of multiple forms of brain monoamine oxidase in situ as probed by electron spin resonance. Spin-labeled hydroxyamphetamine, a competitive reversible inhibitor of brain monoamine oxidase, has been shown to be useful as an electron spin resonance (ESR) probe of the microenvironment of the active sites of the possible monoamine oxidase multiple forms. The ESR spectrum of spin-labeled hydroxyamphetamine was strongly quenched upon binding to the enzyme. The conformation of the active site of rat brain monoamine oxidase existing in various physical states, i.e. monoamine oxidase in situ (intact brain mitochondria), crude solubilized monoamine oxidase (MAOS) and isolated monoamine oxidase fractions (MAOa and MAOb) were critically and systematically examined. Nonlinear least squares regression analyses have been used to fit the binding data (obtained at room temperature with varying spin-labeled hydroxyamphetamine concentrations) to three groups of independent noninteracting ligand-binding models. A Gibbs-Helmholtz relationship was applied to the interpretation of the measured apparent association constant K as a function of temperature ranging from 4-50 degrees with increments of 2 degreesmfrom the extracted intensive parameters, k (intrinsic association constant) and deltaF (intrinsic free energy), as well as the apparent heat, deltaH, it was clear that the microenvironment of the binding sites existing in the more purified enzyme fractions MAOa and MAOb were similar to those found in the crude solubilized enzyme. More importantly, they correlated well with the conformation of the sites characterized in situ. The data suggested that the microenvironment of this multienzyme system was unperturbed in spite of the treatment due to the isolation process. In terms of the composition of binding sites, MAOa appeared to be heterogeneous while MAOb appeared to be more homogeneous. Since the isolated fractions MAOa and MAOb possessed marked different substrate specificities, these observations directly implied that monoamine oxidase multiple forms do exist in situ. The extracted extensive parameters, n (specific binding activity, nanomoles/mg of protein), as well as the measured characteristic transition temperatures, indicated that the relative abundance of the sites which directly affected substrate specificities was indeed altered. The consistency of the characteristic transition temperatures of 21 degrees and 38 degrees for the case of intact membrane preparations was particularly significant. A tenable hypothesis is that the manipulation in the composition of the monoamine oxidase binding forms through intimate lipid-protein interactions, which has been amply demonstrated in many biomembrane systems to be functionally important might be the underlying regulatory mechanism in vivo."}
{"id": "PMID:188807", "title": "Measurement of superhelix densities in buoyant dye/CsCl. The use of a standard other than native SV40 DNA.", "content": "The dye-induced separation between closed and open duplex DNAs in buoyant CsCl is determined primarily by the superhelix density of the closed DNA, provided that all other experimental variables (such as the solution density and dye concentration) are held constant. The extent of the buoyant separation may be used to estimate the superhelix density of an uncharacterized closed DNA, by comparison with the corresponding separation with native SV40 DNAs under identical conditions. We present here an extension of these quantitative relationships to permit the use of an arbitrarily selected closed duplex DNA of known superhelix density, with the accompanying open form, as a reference. The general result is that the ratio of buoyant separations for any two closed/open DNA pairs remains a linear function of the difference in superhelix densities between the closed DNAs. The value of the proportionality constant depends, however, upon the magnitude of the superhelix density of the closed DNA selected as reference.", "contents": "Measurement of superhelix densities in buoyant dye/CsCl. The use of a standard other than native SV40 DNA. The dye-induced separation between closed and open duplex DNAs in buoyant CsCl is determined primarily by the superhelix density of the closed DNA, provided that all other experimental variables (such as the solution density and dye concentration) are held constant. The extent of the buoyant separation may be used to estimate the superhelix density of an uncharacterized closed DNA, by comparison with the corresponding separation with native SV40 DNAs under identical conditions. We present here an extension of these quantitative relationships to permit the use of an arbitrarily selected closed duplex DNA of known superhelix density, with the accompanying open form, as a reference. The general result is that the ratio of buoyant separations for any two closed/open DNA pairs remains a linear function of the difference in superhelix densities between the closed DNAs. The value of the proportionality constant depends, however, upon the magnitude of the superhelix density of the closed DNA selected as reference."}
{"id": "PMID:188810", "title": "Nucleotide sequence of a fragment of SV40 DNA that contains the origin of DNA replication and specifies the 5' ends of \"early\" and \"late\" viral RNA. III. Construction of the total sequence of EcoRII-G fragment of SV40 DNA.", "content": "Limited T1 RNase digestion of subfragments of the SV40 DNA restriction endonuclease fragment EcoRII-G were prepared and analyzed. The fragments were separately labeled with 32P at their 5' terminus and the terminal sequences analyzed with limited snake venom diesterase digestion. The data permitted us to deduce the nucleotide sequence for EcoRII-G. The sequence contains a stretch of 17 A-T base pairs preceding the DNA complementary to the 5' end of \"early\" message RNA, a stretch of 27 bases with a perfect 2-fold rotational symmetry near the origin of DNA replication and a perfect tandem repeat of 21 nucleotides.", "contents": "Nucleotide sequence of a fragment of SV40 DNA that contains the origin of DNA replication and specifies the 5' ends of \"early\" and \"late\" viral RNA. III. Construction of the total sequence of EcoRII-G fragment of SV40 DNA. Limited T1 RNase digestion of subfragments of the SV40 DNA restriction endonuclease fragment EcoRII-G were prepared and analyzed. The fragments were separately labeled with 32P at their 5' terminus and the terminal sequences analyzed with limited snake venom diesterase digestion. The data permitted us to deduce the nucleotide sequence for EcoRII-G. The sequence contains a stretch of 17 A-T base pairs preceding the DNA complementary to the 5' end of \"early\" message RNA, a stretch of 27 bases with a perfect 2-fold rotational symmetry near the origin of DNA replication and a perfect tandem repeat of 21 nucleotides."}
{"id": "PMID:188811", "title": "Nucleotide sequence of a fragment of SV40 DNA that contains the origin of DNA replication and specifies the 5' ends of \"early\" and \"late\" viral RNA. IV. Localization of the SV40 DNA complementary to the 5' ends of viral mRNA.", "content": "Cytoplasmic mRNA isolated from cells infected with SV40 was isolated by passage over oligo(dT)-cellulose columns. This RNA was annealed to SV40 DNA fragments produced by cleavage with EcoRII endonuclease. The RNA resistant to RNase digestion was analyzed by digestion with ribonucleases and oligonucleotide mapping. The results were compared with oligonucleotides from in vitro transcripts of the fragments and with whole genome SV40 cRNA which had been fractionated by hybridization to the fragments. The 5' ends of \"early\" and the large \"late\" SV40 mRNA, transcribed from opposite DNA strands, overlap for a region of 60 to 100 nucleotides. The region of overlap includes a portion of the segment of DNA containing the origin of DNA replication.", "contents": "Nucleotide sequence of a fragment of SV40 DNA that contains the origin of DNA replication and specifies the 5' ends of \"early\" and \"late\" viral RNA. IV. Localization of the SV40 DNA complementary to the 5' ends of viral mRNA. Cytoplasmic mRNA isolated from cells infected with SV40 was isolated by passage over oligo(dT)-cellulose columns. This RNA was annealed to SV40 DNA fragments produced by cleavage with EcoRII endonuclease. The RNA resistant to RNase digestion was analyzed by digestion with ribonucleases and oligonucleotide mapping. The results were compared with oligonucleotides from in vitro transcripts of the fragments and with whole genome SV40 cRNA which had been fractionated by hybridization to the fragments. The 5' ends of \"early\" and the large \"late\" SV40 mRNA, transcribed from opposite DNA strands, overlap for a region of 60 to 100 nucleotides. The region of overlap includes a portion of the segment of DNA containing the origin of DNA replication."}
{"id": "PMID:188812", "title": "Chain equivalence in reaction of nitric oxide with hemoglobin.", "content": "Mixtures of nitric oxide and hemoglobin were prepared in a rapid freeze apparatus and analyzed by EPR spectroscopy. Spectra from samples at various degrees of saturation showed that the two subunits bound NO at equal rates. Identical results were observed in 0.1 M phosphate at pH 6.5 and 0.1 M 2,2'-bis(hydroxymethyl)-2,2',2''-nitrilotriethanol, 0.1 M NaCl at pH 7.0, both in the presence and absence of inositol hexaphosphate at either buffer condition. At subsaturating levels of NO (less than 60%), or at all levels of saturation in the presence of inositol hexaphosphate, it was found that the EPR spectrum of nitrosylhemoglobin varied with the length of time before freezing. This change was characterized by the development of a hyperfine structure at g = 2.01 which appeared with a half-time of approximately 0.4 s. Maxwell and Caughey (Maxwell, J. C., and Caughey, W. S. (1976) Biochemistry 15, 388-395) have attributed this three-line EPR hyperfine structure to the formation of a pentacoordinate ferroheme-NO complex. Corresponding slow changes were observed in the visible absorption spectrum following the binding of low levels of NO to deoxyhemoglobin or inositol hexaphosphate to fully saturated nitrosylhemoglobin. Thus it appears that NO binding to the alpha and beta subunits of deoxyhemoglobin takes place at equal rates and, under conditions favoring the T quaternary state (low saturation, presence of inositol hexaphosphate), a further slow structural change takes place, resulting in the cleavage of the iron--proximal histidine bond.", "contents": "Chain equivalence in reaction of nitric oxide with hemoglobin. Mixtures of nitric oxide and hemoglobin were prepared in a rapid freeze apparatus and analyzed by EPR spectroscopy. Spectra from samples at various degrees of saturation showed that the two subunits bound NO at equal rates. Identical results were observed in 0.1 M phosphate at pH 6.5 and 0.1 M 2,2'-bis(hydroxymethyl)-2,2',2''-nitrilotriethanol, 0.1 M NaCl at pH 7.0, both in the presence and absence of inositol hexaphosphate at either buffer condition. At subsaturating levels of NO (less than 60%), or at all levels of saturation in the presence of inositol hexaphosphate, it was found that the EPR spectrum of nitrosylhemoglobin varied with the length of time before freezing. This change was characterized by the development of a hyperfine structure at g = 2.01 which appeared with a half-time of approximately 0.4 s. Maxwell and Caughey (Maxwell, J. C., and Caughey, W. S. (1976) Biochemistry 15, 388-395) have attributed this three-line EPR hyperfine structure to the formation of a pentacoordinate ferroheme-NO complex. Corresponding slow changes were observed in the visible absorption spectrum following the binding of low levels of NO to deoxyhemoglobin or inositol hexaphosphate to fully saturated nitrosylhemoglobin. Thus it appears that NO binding to the alpha and beta subunits of deoxyhemoglobin takes place at equal rates and, under conditions favoring the T quaternary state (low saturation, presence of inositol hexaphosphate), a further slow structural change takes place, resulting in the cleavage of the iron--proximal histidine bond."}
{"id": "PMID:188813", "title": "Purification of a Ca2+-activatable cyclic nucleotide phosphodiesterase from bovine heart by specific interaction with its Ca2+-dependent modulator protein.", "content": "A Ca2+-activatable cyclic nucleotide phosphodiesterase from bovine heart can be eluted from a DEAE-cellulose column either in the free form by buffers containing 0.1 mM ethylene glycol bis(beta-aminoethyl ether)N-N,N'N'-tetraacetic acid (EGTA) or as a complex of the enzyme with its protein modulator by buffers containing 0.01 mM CaCl2. A purification procedure based primarily on the significantly different affinity of the two forms of the enzyme for DEAE-cellulose was developed for the purification of the enzyme from bovine heart. The procedure involves ammonium sulfate fractionation, three chromatographic steps on DEAE-cellulose, and gel filtration on Sephadex G-200 with a 5000-fold purification over the crude extract. The purified enzyme has a specific activity of 120 mumol of cAMP/mg/min, can be activated 5-fold by Ca2+, but is only 80% pure as judged by analytical disc gel electrophoresis. The purified enzyme is unstable but can be stabilized by addition of Ca2+ and the protein modulator; this is in contrast to the less pure preparations of Ca2+-activatable phosphodiesterase which are destabilized by the protein modulator in the presence of Ca2+.", "contents": "Purification of a Ca2+-activatable cyclic nucleotide phosphodiesterase from bovine heart by specific interaction with its Ca2+-dependent modulator protein. A Ca2+-activatable cyclic nucleotide phosphodiesterase from bovine heart can be eluted from a DEAE-cellulose column either in the free form by buffers containing 0.1 mM ethylene glycol bis(beta-aminoethyl ether)N-N,N'N'-tetraacetic acid (EGTA) or as a complex of the enzyme with its protein modulator by buffers containing 0.01 mM CaCl2. A purification procedure based primarily on the significantly different affinity of the two forms of the enzyme for DEAE-cellulose was developed for the purification of the enzyme from bovine heart. The procedure involves ammonium sulfate fractionation, three chromatographic steps on DEAE-cellulose, and gel filtration on Sephadex G-200 with a 5000-fold purification over the crude extract. The purified enzyme has a specific activity of 120 mumol of cAMP/mg/min, can be activated 5-fold by Ca2+, but is only 80% pure as judged by analytical disc gel electrophoresis. The purified enzyme is unstable but can be stabilized by addition of Ca2+ and the protein modulator; this is in contrast to the less pure preparations of Ca2+-activatable phosphodiesterase which are destabilized by the protein modulator in the presence of Ca2+."}
{"id": "PMID:188814", "title": "Cyclic adenosine 3':5'-monophosphate-mediated insulin secretion and ribosomal protein phosphorylation in a hamster islet cell tumor.", "content": "In order to understand the mechanism by which cyclic 3':5'-adenosine monophosphate (cAMP) regulates insulin secretion, cAMP-dependent protein phosphorylation was studied in a transplantable hamster islet cell tumor. Single cell suspensions prepared by enzymatic digestion of the tumors released insulin into the incubation media. Glucagon (3 nM to 3 muM) stimulated cellular cAMP accumulation and insulin release in a dose-dependent manner and these effects were enhanced by 1 mM theophylline. 8-Bromoadenosine 3':5'-monophosphate (8Br-cAMP) (1 mM) increased insulin  release. Somatostatin (10 mug/ml) inhibited basal and glucagon or 8Br-cAMP-stimulated insulin release without significantly lowering cellular cAMP in glucagon-stimulated cells. For analysis of phosphoproteins, cells were incubated with carrier-free 32Pi following which lysates were prepared and analyzed by sodium dodecyl sulfate slab gel electrophoresis and autoradiography. Of the numerous 32P-labeled protein bands found, only one (P1, Mr = 28,000) displayed a significant increase in 32P incorporation when cells were incubated under conditions that raise the concentration of cellular cAMP. Somatostatin did not affect 32P incorporation into P1 or any other protein band. When cells were incubated with glucagon, an increase in cellular cAMP was evident after 1 min, enhanced 32P incorporation into P1 after 1 to 5 min, and stimulation of insulin release after 5 to 10 min. Analysis of subcellular fractions led to the designation of P1 as a 40 S ribosomal protein. Two-dimensional electrophoresis of 32P-labeled basic ribosomal proteins showed two labeled proteins, P1 and P2, both of which were localized to the 40 S ribosomal subunit. Only phosphorylation of P1 was stimulated by cAMP. The cAMP-dependent ribosomal phosphoprotein, P1, may be identical with a ribosomal phosphoprotein demonstrated in a variety of tissues and species. Its physiological role remains to be established.", "contents": "Cyclic adenosine 3':5'-monophosphate-mediated insulin secretion and ribosomal protein phosphorylation in a hamster islet cell tumor. In order to understand the mechanism by which cyclic 3':5'-adenosine monophosphate (cAMP) regulates insulin secretion, cAMP-dependent protein phosphorylation was studied in a transplantable hamster islet cell tumor. Single cell suspensions prepared by enzymatic digestion of the tumors released insulin into the incubation media. Glucagon (3 nM to 3 muM) stimulated cellular cAMP accumulation and insulin release in a dose-dependent manner and these effects were enhanced by 1 mM theophylline. 8-Bromoadenosine 3':5'-monophosphate (8Br-cAMP) (1 mM) increased insulin  release. Somatostatin (10 mug/ml) inhibited basal and glucagon or 8Br-cAMP-stimulated insulin release without significantly lowering cellular cAMP in glucagon-stimulated cells. For analysis of phosphoproteins, cells were incubated with carrier-free 32Pi following which lysates were prepared and analyzed by sodium dodecyl sulfate slab gel electrophoresis and autoradiography. Of the numerous 32P-labeled protein bands found, only one (P1, Mr = 28,000) displayed a significant increase in 32P incorporation when cells were incubated under conditions that raise the concentration of cellular cAMP. Somatostatin did not affect 32P incorporation into P1 or any other protein band. When cells were incubated with glucagon, an increase in cellular cAMP was evident after 1 min, enhanced 32P incorporation into P1 after 1 to 5 min, and stimulation of insulin release after 5 to 10 min. Analysis of subcellular fractions led to the designation of P1 as a 40 S ribosomal protein. Two-dimensional electrophoresis of 32P-labeled basic ribosomal proteins showed two labeled proteins, P1 and P2, both of which were localized to the 40 S ribosomal subunit. Only phosphorylation of P1 was stimulated by cAMP. The cAMP-dependent ribosomal phosphoprotein, P1, may be identical with a ribosomal phosphoprotein demonstrated in a variety of tissues and species. Its physiological role remains to be established."}
{"id": "PMID:188815", "title": "Cytochrome c turnover in rat skeletal muscles.", "content": "Exercise induces an increase in cytochrome c concentration in skeletal muscle. This adaptation provides an approach to studying the turnover of cytochrome c that avoids the problem of reutilization encountered with isotopic tracers. The half-life of cytochrome c was estimated from the time course of the increase in its concentration to a new, higher, steady state level in response to exercise training, and from the decrease in cytochrome c after cessation of exercise. The half-time of the increase in cytochrome c concentration was approximately 6 days, while the half-time of the decrease was 7 to 8 days in the fast red and slow red types of muscle. The finding that the half-times of the increase and of the decrease in cytochrome c concentration are similar provides evidence that the exercise-induced increase in cytochrome c is due to an increase in its rate of synthesis. These half-times are much shorter than those obtained with isotopic tracers. It had been thought that the heme precursor delta-aminolevulinate is not reutilized. However, the half-time of the decrease in radioactivity of cytochrome c labeled with delta-aminol[14C]levulinate was 45 days, and increased to 60 days in response to exercise, in fast red muscle. The half-time of the decrease in radioactivity of cytochrome c labeled with [(3H)]leucine in gastrocnemius muscle was shorter than with delta-amino[14C]levulinate (18 days compared to 38 days). These results indicate that when delta-amino(14C)levulinate is used to label heme, reutilization is a serious problem in skeletal muscle.", "contents": "Cytochrome c turnover in rat skeletal muscles. Exercise induces an increase in cytochrome c concentration in skeletal muscle. This adaptation provides an approach to studying the turnover of cytochrome c that avoids the problem of reutilization encountered with isotopic tracers. The half-life of cytochrome c was estimated from the time course of the increase in its concentration to a new, higher, steady state level in response to exercise training, and from the decrease in cytochrome c after cessation of exercise. The half-time of the increase in cytochrome c concentration was approximately 6 days, while the half-time of the decrease was 7 to 8 days in the fast red and slow red types of muscle. The finding that the half-times of the increase and of the decrease in cytochrome c concentration are similar provides evidence that the exercise-induced increase in cytochrome c is due to an increase in its rate of synthesis. These half-times are much shorter than those obtained with isotopic tracers. It had been thought that the heme precursor delta-aminolevulinate is not reutilized. However, the half-time of the decrease in radioactivity of cytochrome c labeled with delta-aminol[14C]levulinate was 45 days, and increased to 60 days in response to exercise, in fast red muscle. The half-time of the decrease in radioactivity of cytochrome c labeled with [(3H)]leucine in gastrocnemius muscle was shorter than with delta-amino[14C]levulinate (18 days compared to 38 days). These results indicate that when delta-amino(14C)levulinate is used to label heme, reutilization is a serious problem in skeletal muscle."}
{"id": "PMID:188816", "title": "Phosphorylation in membranes of intact human erythrocytes.", "content": "Studies of phosphorylation in membranes of intact human erythrocytes were performed by incubating erythrocytes in inorganic [32P]phosphate. Analysis of membrane proteins by polyacrylamide gel electrophoresis showed a pattern of phosphorylation similar to that observed when ghost membranes were incubated with [gamma-32P]ATP. Membrane lipid phosphorylation was also similar in intact cells and ghosts. The most heavily phosphorylated lipid, polyphosphoinositide, was closely associated with glycophorin A, the major erythrocyte membrane sialoglycoprotein obtained when the sialoglycoprotein fraction was isolated by the lithium diiodosalicylate-phenol partition procedure. Only 1 molecule of glycophorin A out of every 100 was found to be phosphorylated, and the phosphate exchange occurred specifically in the COOH-terminal intracellular portion of glycophorin A. These studies show that the human erythrocyte can be used as a model for membrane phosphorylation in an intact cell system.", "contents": "Phosphorylation in membranes of intact human erythrocytes. Studies of phosphorylation in membranes of intact human erythrocytes were performed by incubating erythrocytes in inorganic [32P]phosphate. Analysis of membrane proteins by polyacrylamide gel electrophoresis showed a pattern of phosphorylation similar to that observed when ghost membranes were incubated with [gamma-32P]ATP. Membrane lipid phosphorylation was also similar in intact cells and ghosts. The most heavily phosphorylated lipid, polyphosphoinositide, was closely associated with glycophorin A, the major erythrocyte membrane sialoglycoprotein obtained when the sialoglycoprotein fraction was isolated by the lithium diiodosalicylate-phenol partition procedure. Only 1 molecule of glycophorin A out of every 100 was found to be phosphorylated, and the phosphate exchange occurred specifically in the COOH-terminal intracellular portion of glycophorin A. These studies show that the human erythrocyte can be used as a model for membrane phosphorylation in an intact cell system."}
{"id": "PMID:188817", "title": "Effects of beta subunit acylation on lutropin receptor site binding.", "content": "The effects of various modifications on the beta subunit of lutropin have been studied using the binding characteristics of the reconstituted hormone in the rat testicular radioligand assay. Conditions for iodinating lutropin and lutropin derivatives were determined which resulted in 15 per cent specific binding when tested immediately and retention of 6 to 7 per cent specific binding even after storage for 6 months. Acetimidinyl, acetyl, and carbamyl derivatives of the beta subunit were prepared and combined with unmodified alpha subunit to form reconstituted lutropin. Modification of the beta subunit was shown to have no effect on the time course of binding to testicular receptors or, with one exception, on the extent of receptor saturation. Very high concentrations of lutropin reconstituted with acetylated beta subunit showed an anomalous binding behavior. Scatchard plots of the binding data support the view that the native hormone has a unique receptor affinity which is irreversibly disrupted by separation of subunits and that derivatization of the beta subunit does not alter this parameter further. These data also suggest that there are no significant differences in the amino groups modified on the beta subunit. Competition and preincubation tests for receptor sites that reacted only with modified lutropin and not with the native hormone were negative.", "contents": "Effects of beta subunit acylation on lutropin receptor site binding. The effects of various modifications on the beta subunit of lutropin have been studied using the binding characteristics of the reconstituted hormone in the rat testicular radioligand assay. Conditions for iodinating lutropin and lutropin derivatives were determined which resulted in 15 per cent specific binding when tested immediately and retention of 6 to 7 per cent specific binding even after storage for 6 months. Acetimidinyl, acetyl, and carbamyl derivatives of the beta subunit were prepared and combined with unmodified alpha subunit to form reconstituted lutropin. Modification of the beta subunit was shown to have no effect on the time course of binding to testicular receptors or, with one exception, on the extent of receptor saturation. Very high concentrations of lutropin reconstituted with acetylated beta subunit showed an anomalous binding behavior. Scatchard plots of the binding data support the view that the native hormone has a unique receptor affinity which is irreversibly disrupted by separation of subunits and that derivatization of the beta subunit does not alter this parameter further. These data also suggest that there are no significant differences in the amino groups modified on the beta subunit. Competition and preincubation tests for receptor sites that reacted only with modified lutropin and not with the native hormone were negative."}
{"id": "PMID:188818", "title": "Activation of protein kinase and glycogen phosphorylase in isolated rat liver cells by glucagon and catecholamines.", "content": "In liver cells isolated from fed female rats, glucagon (290nM) increased adenosine 3':5'-monophosphate (cyclic AMP) content and decreased cyclic AMP binding 30 s after addition of hormones. Both returned to control values after 10 min. Glucagon also stimulated cyclic AMP-independent protein kinase activity at 30 s and decreased protein kinase activity assayed in the presence of 2 muM cyclic AMP at 1 min. Glucagon increased the levels of glycogen phosphorylase a, but there was no change in total glycogen phosphorylase activity. Glucagon increased glycogen phosphorylase a at concentrations considerably less than those required to affect cyclic AMP and protein kinase. The phosphodiesterase inhibitor, 1-methyl-3-isobutyl xanthine, potentiated the action of glucagon on all variables, but did not increase the maximuM activation of glycogen phosphorylase. Epinephrine (1muM) decreased cyclic AMP binding and increased glycogen phosphorylase a after a 1-min incubation with cells. Although 0.1 muM epinephrine stimulated phosphorylase a, a concentration of 10 muM was required to increase protein kinase activity. 1-Methyl-3-isobutyl xanthine (0.1 mM) potentiated the action of epinephrine on cyclic AMP and protein kinase. (-)-Propranolol (10muM) completely abolished the changes in cyclic AMP binding and protein kinase due to epinephrine (1muM) in the presence of 0.1mM 1-methyl-3-isobutyl xanthine, yet inhibited the increase in phosphorylase a by only 14 per cent. Phenylephrine (0.1muM) increased glycogen phosphorylase a, although concentrations as great as 10 muM failed to affect cyclic AMP binding or protein kinase in the absence of phosphodiesterase inhibitor. Isoproterenol (0.1muM) stimulated phosphorylase and decreased cyclic AMP binding, but only a concentration of 10muM increased protein kinase. 1-Methyl-3-isobutyl xanthine potentiated the action of isoproterenol on cyclic AMP binding and protein kinase, and propranolol reduced the augmentation of glucose release and glycogen phosphorylase activity due to isoproterenol. These data indicate that both alpha- and beta-adrenergic agents are capable of stimulating glycogenolysis and glycogen phosphorylase a in isolated rat liver cells. Low concentrations of glucagon and beta-adrenergic agonists stimulate glycogen phosphorylase without any detectable increase in cyclic AMP or protein kinase activity. The effects of alpha-adrenergic agents appear to be completely independent of changes in cyclic AMP protein kinase activity.", "contents": "Activation of protein kinase and glycogen phosphorylase in isolated rat liver cells by glucagon and catecholamines. In liver cells isolated from fed female rats, glucagon (290nM) increased adenosine 3':5'-monophosphate (cyclic AMP) content and decreased cyclic AMP binding 30 s after addition of hormones. Both returned to control values after 10 min. Glucagon also stimulated cyclic AMP-independent protein kinase activity at 30 s and decreased protein kinase activity assayed in the presence of 2 muM cyclic AMP at 1 min. Glucagon increased the levels of glycogen phosphorylase a, but there was no change in total glycogen phosphorylase activity. Glucagon increased glycogen phosphorylase a at concentrations considerably less than those required to affect cyclic AMP and protein kinase. The phosphodiesterase inhibitor, 1-methyl-3-isobutyl xanthine, potentiated the action of glucagon on all variables, but did not increase the maximuM activation of glycogen phosphorylase. Epinephrine (1muM) decreased cyclic AMP binding and increased glycogen phosphorylase a after a 1-min incubation with cells. Although 0.1 muM epinephrine stimulated phosphorylase a, a concentration of 10 muM was required to increase protein kinase activity. 1-Methyl-3-isobutyl xanthine (0.1 mM) potentiated the action of epinephrine on cyclic AMP and protein kinase. (-)-Propranolol (10muM) completely abolished the changes in cyclic AMP binding and protein kinase due to epinephrine (1muM) in the presence of 0.1mM 1-methyl-3-isobutyl xanthine, yet inhibited the increase in phosphorylase a by only 14 per cent. Phenylephrine (0.1muM) increased glycogen phosphorylase a, although concentrations as great as 10 muM failed to affect cyclic AMP binding or protein kinase in the absence of phosphodiesterase inhibitor. Isoproterenol (0.1muM) stimulated phosphorylase and decreased cyclic AMP binding, but only a concentration of 10muM increased protein kinase. 1-Methyl-3-isobutyl xanthine potentiated the action of isoproterenol on cyclic AMP binding and protein kinase, and propranolol reduced the augmentation of glucose release and glycogen phosphorylase activity due to isoproterenol. These data indicate that both alpha- and beta-adrenergic agents are capable of stimulating glycogenolysis and glycogen phosphorylase a in isolated rat liver cells. Low concentrations of glucagon and beta-adrenergic agonists stimulate glycogen phosphorylase without any detectable increase in cyclic AMP or protein kinase activity. The effects of alpha-adrenergic agents appear to be completely independent of changes in cyclic AMP protein kinase activity."}
{"id": "PMID:188819", "title": "Nature of the free radical in ribonucleotide reductase from Escherichia coli.", "content": "Ribonucleotide reductase from Escherichia coli consists of two nonidentical subunits, proteins B1 and B2. The active site of the enzyme is made up from both subunits. Protein B2 contributes inter alia an organic free radical which gives a characteristic EPR signal. This radical was now located by isotope substitution experiments to the beta position of a tyrosine residue. The EPR spectrum of protein B2 from bacteria grown in a completely deuterated medium was drastically changed. The change was reversed by the addition of other protonated amino acids. The involvement in radical formation of the beta position of tyrosine was demonstrated from EPR spectra of protein B2 from bacteria grown in the presence of specifically deuterated tyrosine.", "contents": "Nature of the free radical in ribonucleotide reductase from Escherichia coli. Ribonucleotide reductase from Escherichia coli consists of two nonidentical subunits, proteins B1 and B2. The active site of the enzyme is made up from both subunits. Protein B2 contributes inter alia an organic free radical which gives a characteristic EPR signal. This radical was now located by isotope substitution experiments to the beta position of a tyrosine residue. The EPR spectrum of protein B2 from bacteria grown in a completely deuterated medium was drastically changed. The change was reversed by the addition of other protonated amino acids. The involvement in radical formation of the beta position of tyrosine was demonstrated from EPR spectra of protein B2 from bacteria grown in the presence of specifically deuterated tyrosine."}
{"id": "PMID:188820", "title": "Studies on cobalt myoglobins and hemoglobins. Preparation of isolated chains containing cobaltous protoporphyrin IX and characterization of their equilibrium and kinetic properties of oxygenation and EPR spectra.", "content": "Human hemoglobin containing cobalt protoporphyrin IX or cobalt hemoglobin has been separated into two functionally active alpha and beta subunits using a new method of subunit separation, in which the -SH groups of the isolated subunits were successfully regenerated by treatment with dithiothreitol in the presence of catalase. Oxygen equilibria of the isolated subunit chains were examined over a wide range of temperature using Imai's polarographic method (Imai, K., Morimoto, H., Kotani, M., Watari, H., and Kuroda, M. (1970) Biochim. Biophys. Acta 200, 189-196). Kinetic properties of their reversible oxygenation were investigated by the temperature jump relaxation method at 16 degrees. Electron paramagnetic resonance characteristics of the molecules in both deoxy and oxy states were studies at 77K. The oxygen affinity of the individual regenerated chains was higher than that of the tetrameric cobalt hemoglobin and was independent of pH. The enthalpy changes of the oxygenation have been determined as -13.8 kcal/mol and -16.8 kcal/mol for the alpha and beta chains, respectively. The rates of oxygenation were similar to those reported for iron hemoglobin chains, whereas those of deoxygenation were about 10(2) times larger. The effects of metal substitution on oxygenation properties of the isolated chains were correlated with the results obtained previously on cobalt hemoglobin and cobalt myoglobin. The EPR spectrum of the oxy alpha chain showed a distinctly narrowed hyperfine structure in comparison with that of the oxy beta chain, indicating that the environment around the paramagnetic center (the bound oxygen) is different between these chains. In the deoxy form, EPR spectra of alpha and beta chains were indistinguishable. These observations suggest that one of the inequivalences between alpha and beta chains might exist near the distal histidine group.", "contents": "Studies on cobalt myoglobins and hemoglobins. Preparation of isolated chains containing cobaltous protoporphyrin IX and characterization of their equilibrium and kinetic properties of oxygenation and EPR spectra. Human hemoglobin containing cobalt protoporphyrin IX or cobalt hemoglobin has been separated into two functionally active alpha and beta subunits using a new method of subunit separation, in which the -SH groups of the isolated subunits were successfully regenerated by treatment with dithiothreitol in the presence of catalase. Oxygen equilibria of the isolated subunit chains were examined over a wide range of temperature using Imai's polarographic method (Imai, K., Morimoto, H., Kotani, M., Watari, H., and Kuroda, M. (1970) Biochim. Biophys. Acta 200, 189-196). Kinetic properties of their reversible oxygenation were investigated by the temperature jump relaxation method at 16 degrees. Electron paramagnetic resonance characteristics of the molecules in both deoxy and oxy states were studies at 77K. The oxygen affinity of the individual regenerated chains was higher than that of the tetrameric cobalt hemoglobin and was independent of pH. The enthalpy changes of the oxygenation have been determined as -13.8 kcal/mol and -16.8 kcal/mol for the alpha and beta chains, respectively. The rates of oxygenation were similar to those reported for iron hemoglobin chains, whereas those of deoxygenation were about 10(2) times larger. The effects of metal substitution on oxygenation properties of the isolated chains were correlated with the results obtained previously on cobalt hemoglobin and cobalt myoglobin. The EPR spectrum of the oxy alpha chain showed a distinctly narrowed hyperfine structure in comparison with that of the oxy beta chain, indicating that the environment around the paramagnetic center (the bound oxygen) is different between these chains. In the deoxy form, EPR spectra of alpha and beta chains were indistinguishable. These observations suggest that one of the inequivalences between alpha and beta chains might exist near the distal histidine group."}
{"id": "PMID:188821", "title": "Effect of Mg2+ concentration on the cAMP-dependent protein kinase-catalyzed activation of rabbit skeletal muscle phosphorylase kinase.", "content": "Phosphorylase kinase was found to be activated and phosphorylated at 10mM Mg2+ by the cAMP-dependent protein kinase-catalyzed reaction ot much higher levels than observed previously when reactions were carried out in 1 to 2 mM Mg2+ (Cohen, P. (1973) Eur. J. Biochem. 34, 1; Hayakawa, T., Perkin, J.P., and Krebs, E.G. (1973) Biochemistry 12, 574). That the reaction at 10 mM Mg2+ is protein kinase-catalyzed is supported by several observations: (a) the reaction is facilitated by the addition of protein kinase; (b) the reaction depends on cAMP when protein kinase holoenzyme is uded; (c) the reaction is not inhibited by 1 mM ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetate which is known to inhibit autoactivation and autophosphorylation of phosphorylase kinase; and (d) the protein inhibitor of protein kinase inhibits this reaction. The phosphorylation and activation of phosphorylase kinase seem to occur in two phases. At low Mg2+ only the first phase is manifested and involves the incorporation of 2 mol of phosphate, 1 mol into each of Subunits A and B. At high Mg2+ additional sites are phosphorylated almost exclusively on Subunit A, with phosphate incorporation approaching the final level of 7 to 9 mol. Enzyme activity at high Mg2+ is 2 to 3 times higher than that observed when activation is studied at low Mg2+. The observation that both casein and type II histone are phosphorylated to the same extent at 1 mM and 10 mM Mg2+ suggested that high Mg2+ may be altering the conformation of phosphorylase kinase thus rendering more phosphorylation sites accessible to protein kinase. Since the phosphorylation of phosphorylase kinase by either the protein kinase-catalyzed or autocatalytic reaction can result in the incorporation of 7 to 9 mol of phosphate, the finding that only about seven sites become phosphorylated by both mechanisms acting together suggest that activation by these two mechanisms may involve common phosphorylation sites.", "contents": "Effect of Mg2+ concentration on the cAMP-dependent protein kinase-catalyzed activation of rabbit skeletal muscle phosphorylase kinase. Phosphorylase kinase was found to be activated and phosphorylated at 10mM Mg2+ by the cAMP-dependent protein kinase-catalyzed reaction ot much higher levels than observed previously when reactions were carried out in 1 to 2 mM Mg2+ (Cohen, P. (1973) Eur. J. Biochem. 34, 1; Hayakawa, T., Perkin, J.P., and Krebs, E.G. (1973) Biochemistry 12, 574). That the reaction at 10 mM Mg2+ is protein kinase-catalyzed is supported by several observations: (a) the reaction is facilitated by the addition of protein kinase; (b) the reaction depends on cAMP when protein kinase holoenzyme is uded; (c) the reaction is not inhibited by 1 mM ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetate which is known to inhibit autoactivation and autophosphorylation of phosphorylase kinase; and (d) the protein inhibitor of protein kinase inhibits this reaction. The phosphorylation and activation of phosphorylase kinase seem to occur in two phases. At low Mg2+ only the first phase is manifested and involves the incorporation of 2 mol of phosphate, 1 mol into each of Subunits A and B. At high Mg2+ additional sites are phosphorylated almost exclusively on Subunit A, with phosphate incorporation approaching the final level of 7 to 9 mol. Enzyme activity at high Mg2+ is 2 to 3 times higher than that observed when activation is studied at low Mg2+. The observation that both casein and type II histone are phosphorylated to the same extent at 1 mM and 10 mM Mg2+ suggested that high Mg2+ may be altering the conformation of phosphorylase kinase thus rendering more phosphorylation sites accessible to protein kinase. Since the phosphorylation of phosphorylase kinase by either the protein kinase-catalyzed or autocatalytic reaction can result in the incorporation of 7 to 9 mol of phosphate, the finding that only about seven sites become phosphorylated by both mechanisms acting together suggest that activation by these two mechanisms may involve common phosphorylation sites."}
{"id": "PMID:188822", "title": "Increase in level of functional messenger RNA coding for phosphoenolpyruvate carboxykinase (GTP) during induction by cyclic adenosine 3':5'-monophosphate.", "content": "The administration of N6, O2'-dibutyryl cyclic AMP and theophylline to fasted-refed rats produces an 8-fold stimulation of the relative rate of hepatic phosphoenolpyruvate carboxykinase synthesis in 90 min, as measured by isotopic immunochemical techniques in vivo. The mechanism of this induction was studied first by using a homologous, noninitiating cell-free protein-synthesizing system derived from the liver of fasted-refed, cyclic AMP-treated rats. In such a system, a 5-fold increase in phosphoenolpyruvate carboxykinase synthseis is observed at 20 min post-treatment and a 9-fold stimulation at 75 min, indicating a rapid increase in the number of ribosomes engaged in the translation of the enzyme mRNA after exposure to cyclic AMP. The level of functional mRNA coding for phosphoenolpyruvate carboxykinase was then assayed in a wheat germ protein-synthesizing system capable of using rat liver mRNA as template. The template activity for phosphoenolpyruvate carboxykinase synthesis is greatly increased in the poly(A)-containing RNA isolated from cyclic AMP-induced animals. Both the increase in the capacity of the liver extract for in vitro phosphoenolpyruvate carboxykinase synthesis and the emergence of enzyme mRNA detected in the wheat germ assay are completely prevented by a pretreatment with cordycepin at doses which inhibit the appearance in the cytoplasm of newly synthesized poly(A)-containing RNA. These data demonstrate that the induction of hepatic phosphoenolpyruvate carboxykinase by cyclic AMP is characterized by the rapid build-up of newly synthesized, actively translated mRNA coding for the enzyme. The messenger accumulation could be due to an increase in the rate of its production or a decrease in the rate of its degradation.", "contents": "Increase in level of functional messenger RNA coding for phosphoenolpyruvate carboxykinase (GTP) during induction by cyclic adenosine 3':5'-monophosphate. The administration of N6, O2'-dibutyryl cyclic AMP and theophylline to fasted-refed rats produces an 8-fold stimulation of the relative rate of hepatic phosphoenolpyruvate carboxykinase synthesis in 90 min, as measured by isotopic immunochemical techniques in vivo. The mechanism of this induction was studied first by using a homologous, noninitiating cell-free protein-synthesizing system derived from the liver of fasted-refed, cyclic AMP-treated rats. In such a system, a 5-fold increase in phosphoenolpyruvate carboxykinase synthseis is observed at 20 min post-treatment and a 9-fold stimulation at 75 min, indicating a rapid increase in the number of ribosomes engaged in the translation of the enzyme mRNA after exposure to cyclic AMP. The level of functional mRNA coding for phosphoenolpyruvate carboxykinase was then assayed in a wheat germ protein-synthesizing system capable of using rat liver mRNA as template. The template activity for phosphoenolpyruvate carboxykinase synthesis is greatly increased in the poly(A)-containing RNA isolated from cyclic AMP-induced animals. Both the increase in the capacity of the liver extract for in vitro phosphoenolpyruvate carboxykinase synthesis and the emergence of enzyme mRNA detected in the wheat germ assay are completely prevented by a pretreatment with cordycepin at doses which inhibit the appearance in the cytoplasm of newly synthesized poly(A)-containing RNA. These data demonstrate that the induction of hepatic phosphoenolpyruvate carboxykinase by cyclic AMP is characterized by the rapid build-up of newly synthesized, actively translated mRNA coding for the enzyme. The messenger accumulation could be due to an increase in the rate of its production or a decrease in the rate of its degradation."}
{"id": "PMID:188823", "title": "An adenosine 3':5'-monophosphate-adenosine binding protein from mouse liver.", "content": "A cyclic AMP-adenosine binding protein from mouse liver has been purified to apparent homogeneity as judged by polyacrylamide gel electrophoresis in the absence and presence of sodium dodecyl sulfate and by analytical ultracentrifugation. The binding protein had a Stokes radium of 48 A based on gel chromatography. Both the purified binding protein and the binding activity in fresh cytosol sedimented as 9 S on sucrose gradient centrifugation. The homogeneous protein had a sedimentation coefficient (S20, w) of 8.8 x 10-13 s, as calculated from sedimentation velocity experiments. By use of the Stokes radius and S20, w', the molecular weight was calculated to be 180,000. The protein was composed of polypeptides having the same molecular weight of 45,000 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and thus appeared to consist of four subunits of equal size. The isoelectric point, pI = 5.7. The binding capacity for cyclic AMP increased by preincubating the receptor protein in the presence of Mg2+ ATP. This process, tentatively termed activation, was studied in some detail and was shown not be be be accompanied by dissociation, aggregation, or phosphorylation of the binding protein. Cyclic AMP was bound to the protein with an apparent dissociation constant (Kd) of 1.5 x 10-7 M. The binding of cyclic AMP was competitively inhibited by adenosine, AMP, ADP, and ATP whose inhibition constants were 8 x 10-7 M, 1.2X 10-6 M, 1.5 X 10-6 M, and higher than 5 x 10-6 M respectively. A hyperbolic Scatchard plot was obtained for the binding of adenosine to the activated binding protein, indicating more than one site for adenosine. The binding of adenosine to the site with the highest affinity (Kd=2 x 10-7 M) for this nucleoside was not suppressed by excess cyclic AMP and was thus different from the aforementioned cyclic AMP binding site. Cyclic GMP, GMP, guanosine, cyclic IMP, IMP, and inosine did not inhibit the binding of either cyclic AMP or adenosine. The binding protein had no cyclic AMP phosphodiesterase, adenosine deaminase, phosphofructokinase, or protein kinase activities, nor does it inhibit the catalytic subunit of the cyclic AMP-dependent protein kinase.", "contents": "An adenosine 3':5'-monophosphate-adenosine binding protein from mouse liver. A cyclic AMP-adenosine binding protein from mouse liver has been purified to apparent homogeneity as judged by polyacrylamide gel electrophoresis in the absence and presence of sodium dodecyl sulfate and by analytical ultracentrifugation. The binding protein had a Stokes radium of 48 A based on gel chromatography. Both the purified binding protein and the binding activity in fresh cytosol sedimented as 9 S on sucrose gradient centrifugation. The homogeneous protein had a sedimentation coefficient (S20, w) of 8.8 x 10-13 s, as calculated from sedimentation velocity experiments. By use of the Stokes radius and S20, w', the molecular weight was calculated to be 180,000. The protein was composed of polypeptides having the same molecular weight of 45,000 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and thus appeared to consist of four subunits of equal size. The isoelectric point, pI = 5.7. The binding capacity for cyclic AMP increased by preincubating the receptor protein in the presence of Mg2+ ATP. This process, tentatively termed activation, was studied in some detail and was shown not be be be accompanied by dissociation, aggregation, or phosphorylation of the binding protein. Cyclic AMP was bound to the protein with an apparent dissociation constant (Kd) of 1.5 x 10-7 M. The binding of cyclic AMP was competitively inhibited by adenosine, AMP, ADP, and ATP whose inhibition constants were 8 x 10-7 M, 1.2X 10-6 M, 1.5 X 10-6 M, and higher than 5 x 10-6 M respectively. A hyperbolic Scatchard plot was obtained for the binding of adenosine to the activated binding protein, indicating more than one site for adenosine. The binding of adenosine to the site with the highest affinity (Kd=2 x 10-7 M) for this nucleoside was not suppressed by excess cyclic AMP and was thus different from the aforementioned cyclic AMP binding site. Cyclic GMP, GMP, guanosine, cyclic IMP, IMP, and inosine did not inhibit the binding of either cyclic AMP or adenosine. The binding protein had no cyclic AMP phosphodiesterase, adenosine deaminase, phosphofructokinase, or protein kinase activities, nor does it inhibit the catalytic subunit of the cyclic AMP-dependent protein kinase."}
{"id": "PMID:188824", "title": "Activation of steroidogenesis and adenylate cyclase by adenosine in adrenal and Leydig tumor cells.", "content": "Steroidogenesis by Y-1 adrenal tumor cells in culture is stimulated by ATP, adenyl-5'-yl imidodiphosphate (App(NH)), adenosine 5'(beta, alpha-methylene)triphosphate (App(CH2)p), ADP, AMP, NAD, FAD, and adenosine but not by adenine or other nucleoside triphosphates. ATP, App(NH)p, App(CH2)p, and adenosine are active in the micromolar range. Like adrenocorticotropic hormone (ACTH), the onset of stimulation is immediate and occurs to the same extent. Also active are 2'- and 5'-deoxyadenosine and 2-chloroadenosine whereas adenine xyloside, L-riboside, or arabinoside have very low activity. Stimulation is accompanied by rounding of the cells. Dipyridamole, an inhibitor of adenosine transport, increased the response to low concentrations of adenosine, suggesting that adenosine acts externally. Stimulation of steroidogenesis by adenosine or phosphorylated adenosine compounds fails to occur in the presence of crystalline adenosine deaminase, and the effect of the enzyme on adenosine, ATP, or NAD stimulation is reversed by the competitive inhibitor erythro-9-[3-(nonane-2-ol)]adenine. This suggests that the enzyme acts specifically on adenosine and a requirement for the conversion of the above compounds to adenosine seems probable. The inhibition of cAMP effects by adenosine deaminase suggests that some of its effects are also mediated by conversion to adenosine. Similar stimulation is seen in I-10 Leydig tumor cells, but an ACTH-resistant mutant of Y-1 cells, called OS-3, is relatively resistant to adenosine. Adenosine and 2-chloroadenosine stimulate adenylate cyclase in membranes from Y-1 and I-10 cells at concentrations slightly greater than are effective for steroidogenesis. Other nucleosides are ineffective. Like the NH2-terminal 24 residues of adrenocorticotropic hormone (1-24 ACTH), the adenosine effect in Y-1 membranes is rapid and is on the Vmax intercept (versus ATP) and not on the Km. In contrast to steroidogenesis, adenosine is only a partial agonist for adenylate cyclase. It effect occurs in the presence of ITP, GTP, or guanyl-5'-yl imidodiphosphate (Gpp(NH)p). Theophylline inhibits adenosine-stimulated steroidogenesis. Inhibition of adenylate cyclase occurs in the same concentration range but is of the mixed type.", "contents": "Activation of steroidogenesis and adenylate cyclase by adenosine in adrenal and Leydig tumor cells. Steroidogenesis by Y-1 adrenal tumor cells in culture is stimulated by ATP, adenyl-5'-yl imidodiphosphate (App(NH)), adenosine 5'(beta, alpha-methylene)triphosphate (App(CH2)p), ADP, AMP, NAD, FAD, and adenosine but not by adenine or other nucleoside triphosphates. ATP, App(NH)p, App(CH2)p, and adenosine are active in the micromolar range. Like adrenocorticotropic hormone (ACTH), the onset of stimulation is immediate and occurs to the same extent. Also active are 2'- and 5'-deoxyadenosine and 2-chloroadenosine whereas adenine xyloside, L-riboside, or arabinoside have very low activity. Stimulation is accompanied by rounding of the cells. Dipyridamole, an inhibitor of adenosine transport, increased the response to low concentrations of adenosine, suggesting that adenosine acts externally. Stimulation of steroidogenesis by adenosine or phosphorylated adenosine compounds fails to occur in the presence of crystalline adenosine deaminase, and the effect of the enzyme on adenosine, ATP, or NAD stimulation is reversed by the competitive inhibitor erythro-9-[3-(nonane-2-ol)]adenine. This suggests that the enzyme acts specifically on adenosine and a requirement for the conversion of the above compounds to adenosine seems probable. The inhibition of cAMP effects by adenosine deaminase suggests that some of its effects are also mediated by conversion to adenosine. Similar stimulation is seen in I-10 Leydig tumor cells, but an ACTH-resistant mutant of Y-1 cells, called OS-3, is relatively resistant to adenosine. Adenosine and 2-chloroadenosine stimulate adenylate cyclase in membranes from Y-1 and I-10 cells at concentrations slightly greater than are effective for steroidogenesis. Other nucleosides are ineffective. Like the NH2-terminal 24 residues of adrenocorticotropic hormone (1-24 ACTH), the adenosine effect in Y-1 membranes is rapid and is on the Vmax intercept (versus ATP) and not on the Km. In contrast to steroidogenesis, adenosine is only a partial agonist for adenylate cyclase. It effect occurs in the presence of ITP, GTP, or guanyl-5'-yl imidodiphosphate (Gpp(NH)p). Theophylline inhibits adenosine-stimulated steroidogenesis. Inhibition of adenylate cyclase occurs in the same concentration range but is of the mixed type."}
{"id": "PMID:188825", "title": "Structure and interactions of lipids in human plasma low density lipoproteins.", "content": "Temperature-dependent techniques (differential scanning calorimetry, polarizing microscopy, and x-ray scattering and diffraction techniques) were used to compare the properties of human plasma low density lipoproteins (LDL) with its extracted lipid classes. Three types of thermal transitions were characterized: (a) a reversible transition in intact LDL near body temperature associated with a liquid crystalline order-disorder phase change of cholesterol esters within the particles; (b) an irreversible high temperature transition (approximately 70-90 degrees) associated with LDL denaturation and release of cholesterol esters from the disrupted particles; and (c) low temperature transitions related to liquid crystalline and crystalline phase changes in these released esters. The temperature of the reversible transition in intact LDL varies among individual donors. Correlation analysis shows that the temperature of this transition negatively correlates with the amount of triglyceride relative to cholesterol ester in LDL. Studies on mixtures of cholesterol esters and triglycerides isolated from LDL show a similar effect, increasing amounts of triglycerides decreasing the temperature of the liquid leads to smectic liquid crystalline transition of the isolated esters. Thus, the amount of triglyceride in LDL influences the fluidity of the cholesterol esters in LDL. The enthalpy of the reversible transition in intact LDL is 0.69 cal/g of LDL cholesterol ester. This compares with 0.89 cal/g for the liquid leads to liquid crystalline transition of the cholesterol esters released from denatured LDL and 1.01 cal/g for the same transition in the extracted esters. Unlike the cholesterol esters released from denatured LDL, or isolated LDL esters, cholesterol ester in the intact LDL particle does not crystallize. These findings suggest that the behavior of cholesterol esters in intact LDL is constrained relative to their behavior when freed from the restrictions of the particle. These results together with experiments on partitioning of the individual lipid classes of LDL allow us to define the distribution and interaction of lipids in the intact LDL particle.", "contents": "Structure and interactions of lipids in human plasma low density lipoproteins. Temperature-dependent techniques (differential scanning calorimetry, polarizing microscopy, and x-ray scattering and diffraction techniques) were used to compare the properties of human plasma low density lipoproteins (LDL) with its extracted lipid classes. Three types of thermal transitions were characterized: (a) a reversible transition in intact LDL near body temperature associated with a liquid crystalline order-disorder phase change of cholesterol esters within the particles; (b) an irreversible high temperature transition (approximately 70-90 degrees) associated with LDL denaturation and release of cholesterol esters from the disrupted particles; and (c) low temperature transitions related to liquid crystalline and crystalline phase changes in these released esters. The temperature of the reversible transition in intact LDL varies among individual donors. Correlation analysis shows that the temperature of this transition negatively correlates with the amount of triglyceride relative to cholesterol ester in LDL. Studies on mixtures of cholesterol esters and triglycerides isolated from LDL show a similar effect, increasing amounts of triglycerides decreasing the temperature of the liquid leads to smectic liquid crystalline transition of the isolated esters. Thus, the amount of triglyceride in LDL influences the fluidity of the cholesterol esters in LDL. The enthalpy of the reversible transition in intact LDL is 0.69 cal/g of LDL cholesterol ester. This compares with 0.89 cal/g for the liquid leads to liquid crystalline transition of the cholesterol esters released from denatured LDL and 1.01 cal/g for the same transition in the extracted esters. Unlike the cholesterol esters released from denatured LDL, or isolated LDL esters, cholesterol ester in the intact LDL particle does not crystallize. These findings suggest that the behavior of cholesterol esters in intact LDL is constrained relative to their behavior when freed from the restrictions of the particle. These results together with experiments on partitioning of the individual lipid classes of LDL allow us to define the distribution and interaction of lipids in the intact LDL particle."}
{"id": "PMID:188826", "title": "Tuna cytochrome c at 2.0 A resolution. II. Ferrocytochrome structure analysis.", "content": "The x-ray crystal structure analysis of tuna ferrocytochrome c has been extended from 2.45 to 2.0 A resolution. The overall folding is unchanged and is the same as has been reported for tuna ferricytochrome c (Swanson R., Trus, B.L., Mandel, N., Mandel, G., Kallai, O.B., and Dickerson, R.E. (1977) J. Biol. Chem. 252, 759-755). No significant structural differences are observed between oxidation states. Difference map studies using reoxidized crystals of ferrocytochrome c confirm the absence of a conformation change. A detailed analysis of hydrogen bonding shows the presence of six beta or 310 bends of type II with obligatory glycines in the 3rd residue position. This explains 6 of the 10 nearly invariant glycines in the molecule. Close packing contacts account for three more, and only the invariant glycine 1 remains a mystery.", "contents": "Tuna cytochrome c at 2.0 A resolution. II. Ferrocytochrome structure analysis. The x-ray crystal structure analysis of tuna ferrocytochrome c has been extended from 2.45 to 2.0 A resolution. The overall folding is unchanged and is the same as has been reported for tuna ferricytochrome c (Swanson R., Trus, B.L., Mandel, N., Mandel, G., Kallai, O.B., and Dickerson, R.E. (1977) J. Biol. Chem. 252, 759-755). No significant structural differences are observed between oxidation states. Difference map studies using reoxidized crystals of ferrocytochrome c confirm the absence of a conformation change. A detailed analysis of hydrogen bonding shows the presence of six beta or 310 bends of type II with obligatory glycines in the 3rd residue position. This explains 6 of the 10 nearly invariant glycines in the molecule. Close packing contacts account for three more, and only the invariant glycine 1 remains a mystery."}
{"id": "PMID:188827", "title": "Competence of soluble cell extracts as microtubule assembly systems. Comparison of simian virus 40 transformed and nontransformed mouse 3T3 fibroblasts.", "content": "Soluble cell extracts from simian virus 40 transformed mouse 3T3 fibroblast cells (SV101) and nontransformed mouse BALB/c-3T3 cells were compared as microtubule assembly systems. Extracts from the transformant were found to be at least as competent for microtubule assembly under standard conditions as those from normal cells. This observation proves that the defects in cytoplasmic microtubule skeletons reported in the literature for various transformed cell lines are not due to the loss of integrity of the tubulin molecule itself, but rather to transformation-dependent changes in the regulatory mechanisms controlling in vivo microtubule assembly.", "contents": "Competence of soluble cell extracts as microtubule assembly systems. Comparison of simian virus 40 transformed and nontransformed mouse 3T3 fibroblasts. Soluble cell extracts from simian virus 40 transformed mouse 3T3 fibroblast cells (SV101) and nontransformed mouse BALB/c-3T3 cells were compared as microtubule assembly systems. Extracts from the transformant were found to be at least as competent for microtubule assembly under standard conditions as those from normal cells. This observation proves that the defects in cytoplasmic microtubule skeletons reported in the literature for various transformed cell lines are not due to the loss of integrity of the tubulin molecule itself, but rather to transformation-dependent changes in the regulatory mechanisms controlling in vivo microtubule assembly."}
{"id": "PMID:188828", "title": "Adult-onset vitamin D-resistant hypophosphatemic osteomalacia. A possible variant of vitamin D-resistant rickets.", "content": "A family of 133 members showing unusual manifestations of vitamin D-resistant hypophosphatemic osteomalacia was studied. The hypophosphatemic children did not have rickets or clinical femoral bowing: the hypophosphatemic young adults had minimum clinically evident femoral bowing; and the older adults (age forty and older) were progressively disabled by severe bowing. The disorder appears to be an X-linked dominant, with almost complete penetrance of the hypophosphatemic trait. The etiology of this disorder could not be determined.", "contents": "Adult-onset vitamin D-resistant hypophosphatemic osteomalacia. A possible variant of vitamin D-resistant rickets. A family of 133 members showing unusual manifestations of vitamin D-resistant hypophosphatemic osteomalacia was studied. The hypophosphatemic children did not have rickets or clinical femoral bowing: the hypophosphatemic young adults had minimum clinically evident femoral bowing; and the older adults (age forty and older) were progressively disabled by severe bowing. The disorder appears to be an X-linked dominant, with almost complete penetrance of the hypophosphatemic trait. The etiology of this disorder could not be determined."}
{"id": "PMID:188829", "title": "Structural and biochemical aspects of cell motility in amebas of Dictyostelium discoideum.", "content": "Amebas of Dictyostelium discoideum contain both microfilaments and microtubules. Microfilaments, found primarily in a cortical filament network, aggregate into bundles when glycerinated cells contract in response to Mg-ATP. These cortical filaments bind heavy meromyosin. Microtubules are sparse in amebas before aggregation. Colchicine, griseofulvin, or cold treatments do not affect cell motility or cell shape. Saltatory movement of cytoplasmic particles is inhibited by these treatments and the particles subsequently accumulate in the posterior of the cell. Cell motility rate changes as Dicytostelium amebas go through different stages of the life cycle. Quantitation of cellular actin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that the quantity of cellular actin changes during the life cycle. These changes in actin are directly correlated with changes in motility rate. Addition of cyclic AMP to Dictyostelium cultures at the end of the feeding stage prevents a decline in motility rate during the preaggregation stage. Cyclic AMP also modifies the change in actin content of the cells during preaggregation.", "contents": "Structural and biochemical aspects of cell motility in amebas of Dictyostelium discoideum. Amebas of Dictyostelium discoideum contain both microfilaments and microtubules. Microfilaments, found primarily in a cortical filament network, aggregate into bundles when glycerinated cells contract in response to Mg-ATP. These cortical filaments bind heavy meromyosin. Microtubules are sparse in amebas before aggregation. Colchicine, griseofulvin, or cold treatments do not affect cell motility or cell shape. Saltatory movement of cytoplasmic particles is inhibited by these treatments and the particles subsequently accumulate in the posterior of the cell. Cell motility rate changes as Dicytostelium amebas go through different stages of the life cycle. Quantitation of cellular actin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that the quantity of cellular actin changes during the life cycle. These changes in actin are directly correlated with changes in motility rate. Addition of cyclic AMP to Dictyostelium cultures at the end of the feeding stage prevents a decline in motility rate during the preaggregation stage. Cyclic AMP also modifies the change in actin content of the cells during preaggregation."}
{"id": "PMID:188830", "title": "Dibutyryl cyclic AMP treatment of 3T3 and SV40 virus-transformed 3T3 cells in aggregates. Effects on mobility and cell contact ultrastructure.", "content": "The random cell movement of BALB/c 3T3 and SV40 virus-transformed BALB/c 3T3 cells within homogeneous aggregates was studied by observing the degree of penetration of newly attached [3H]thymidine-labeled cells into the interior of the aggregates. The 3T3 cells penetrated into 3T3 aggregates an average of 0.89 cell diameter in 1.5 days, whereas the SV40-3T3 cells penetrated into SV40-3T3 aggregates an average of 3.20 cell diameters in the same time. Treatment of the aggregates with theophylline, theophylline plus prostaglandin E1, or theophylline plus dibutyryl cyclic AMP all decreased the penetration of the SV40-3T3 cells into SV40-3T3 aggregates (2.36, 1.22, and 0.79 cell diameters, respectively). The same treatments had little effect on 3T3 aggregates. The ultrastructure of 3T3 and SV40-3T3 cells in aggregates was examined by transmission electron microscopy. The 3T3 cells in aggregates were surrounded by microvilli and lamellipodia which were in contact with neighboring cells, whereas SV40-3T3 cells were nearly devoid of microvilli and lamellipodia and made contact at broader, less regular surface undulations. Treatment with theophylline plus dibutyryl cyclic AMP resulted in the appearance of microvilli on SV40-3T3 cells and also appeared to increase the area of intercellular contacts in both 3T3 and SV40-3T3 cells. These observations were supported for the surface cells of the aggregates by scanning electron microscopy.", "contents": "Dibutyryl cyclic AMP treatment of 3T3 and SV40 virus-transformed 3T3 cells in aggregates. Effects on mobility and cell contact ultrastructure. The random cell movement of BALB/c 3T3 and SV40 virus-transformed BALB/c 3T3 cells within homogeneous aggregates was studied by observing the degree of penetration of newly attached [3H]thymidine-labeled cells into the interior of the aggregates. The 3T3 cells penetrated into 3T3 aggregates an average of 0.89 cell diameter in 1.5 days, whereas the SV40-3T3 cells penetrated into SV40-3T3 aggregates an average of 3.20 cell diameters in the same time. Treatment of the aggregates with theophylline, theophylline plus prostaglandin E1, or theophylline plus dibutyryl cyclic AMP all decreased the penetration of the SV40-3T3 cells into SV40-3T3 aggregates (2.36, 1.22, and 0.79 cell diameters, respectively). The same treatments had little effect on 3T3 aggregates. The ultrastructure of 3T3 and SV40-3T3 cells in aggregates was examined by transmission electron microscopy. The 3T3 cells in aggregates were surrounded by microvilli and lamellipodia which were in contact with neighboring cells, whereas SV40-3T3 cells were nearly devoid of microvilli and lamellipodia and made contact at broader, less regular surface undulations. Treatment with theophylline plus dibutyryl cyclic AMP resulted in the appearance of microvilli on SV40-3T3 cells and also appeared to increase the area of intercellular contacts in both 3T3 and SV40-3T3 cells. These observations were supported for the surface cells of the aggregates by scanning electron microscopy."}
{"id": "PMID:188831", "title": "Mitogen-stimulated glucose transport in thymocytes. Possible role of Ca++ and antagonism by adenosine 3':5'-monophosphate.", "content": "The plant lectin, concanavalin A (Con-A), and the ionophore, A-23187 (specific for divalent cations), stimulated glucose transport in rat thymocytes. Con-A stimulation developed more slowly and was somewhat less extensive than that of stimulation developed more slowly and was somewhat less extensive than that of A-23187. Both responses showed saturation dose dependencies. The two responses were poorly additive, suggesting that A-23187 may saturate regulatory processes shared by the two stimulatory mechanisms. Doses of methylisobutylxanthine (MIX) and prostaglandin E2 which raised adenosine 3':5'-monophosphate (cAMP) levels in these cells also antagonized the Con-A stimulation of glucose transport but did not inhibit basal glucose transport or the A-23187 stimulation. Dibutyryl-cAMP and 8-bromo-cAMP also natagonized Con-A stimulation without inhibiting basal glucose transport. MIX antagonized high Con-A doses about as strongly as it did low Con-A doses, suggesting that MIX did not compete in the Con-A binding step or other process saturable by Con-A. [3H-A1Con-A binding was not affected by MIX. The stimulatory effects of Con-A and A-23187 were reduced by reduction of Ca++ in the medium. Both Con-A and A-23187 enhanced 45Ca++ influx and cellular Ca++ content. The A-23187 dose, which was saturating for glucose transport stimulation, enhanced Ca++ influx and cellular Ca++ content more than did the Con-A dose which was saturating for glucose transport stimulation. The dose fo MIX which specifically antagonized Con-A stimulation of glucose transport proved also to reduce Ca++ influx and cellular Ca++ in the presence of Con-A but not in the presence of A-23187. Thus, glucose transport correlates rather well with cellular Ca++. These results are compatible with the view that Ca++ in a cellular compartment can promote glucose transport, the Con-A's enhancement of Ca++ entry contributes to its stimulation of glucose transport, and the MIX antagonized Con-A action at least partly by reducing Ca++ entry. The action of MIX is apparently mediated by cAMP.", "contents": "Mitogen-stimulated glucose transport in thymocytes. Possible role of Ca++ and antagonism by adenosine 3':5'-monophosphate. The plant lectin, concanavalin A (Con-A), and the ionophore, A-23187 (specific for divalent cations), stimulated glucose transport in rat thymocytes. Con-A stimulation developed more slowly and was somewhat less extensive than that of stimulation developed more slowly and was somewhat less extensive than that of A-23187. Both responses showed saturation dose dependencies. The two responses were poorly additive, suggesting that A-23187 may saturate regulatory processes shared by the two stimulatory mechanisms. Doses of methylisobutylxanthine (MIX) and prostaglandin E2 which raised adenosine 3':5'-monophosphate (cAMP) levels in these cells also antagonized the Con-A stimulation of glucose transport but did not inhibit basal glucose transport or the A-23187 stimulation. Dibutyryl-cAMP and 8-bromo-cAMP also natagonized Con-A stimulation without inhibiting basal glucose transport. MIX antagonized high Con-A doses about as strongly as it did low Con-A doses, suggesting that MIX did not compete in the Con-A binding step or other process saturable by Con-A. [3H-A1Con-A binding was not affected by MIX. The stimulatory effects of Con-A and A-23187 were reduced by reduction of Ca++ in the medium. Both Con-A and A-23187 enhanced 45Ca++ influx and cellular Ca++ content. The A-23187 dose, which was saturating for glucose transport stimulation, enhanced Ca++ influx and cellular Ca++ content more than did the Con-A dose which was saturating for glucose transport stimulation. The dose fo MIX which specifically antagonized Con-A stimulation of glucose transport proved also to reduce Ca++ influx and cellular Ca++ in the presence of Con-A but not in the presence of A-23187. Thus, glucose transport correlates rather well with cellular Ca++. These results are compatible with the view that Ca++ in a cellular compartment can promote glucose transport, the Con-A's enhancement of Ca++ entry contributes to its stimulation of glucose transport, and the MIX antagonized Con-A action at least partly by reducing Ca++ entry. The action of MIX is apparently mediated by cAMP."}
{"id": "PMID:188833", "title": "The application of rapid kinetic techniques to the transport of thymidine and 3-O-Methylglucose into Mammalian cells in suspension culture.", "content": "Techniques are described by which the transport of nutrients into mammalian cells in suspension can be measured at intervals of 1.5 seconds. By application of these techniques, the existence of a saturable (Km = 85 muM), non-concentrative, transport system for thymidine was demonstrated in Novikoff rat hepatoma cells depleted of ATP. At concentrations of thymidine less than the Km, this system operated at velocities sufficient to nearly completely equilibrate intra- and extra-cellular thymidine pools within 8 seconds. In phosphorylating cells, the transport system operated with similar rapidity, so that intracellular phosphorylation was rate-limiting for the incorporation of thymidine into nucleotides. Uptake of 3-O-methylglucose occurred at comparable velocities, attaining 90% of equilibrium between internal and external pools within 25 seconds. Uptake of cytosine by simple diffusion was 100 times slower.", "contents": "The application of rapid kinetic techniques to the transport of thymidine and 3-O-Methylglucose into Mammalian cells in suspension culture. Techniques are described by which the transport of nutrients into mammalian cells in suspension can be measured at intervals of 1.5 seconds. By application of these techniques, the existence of a saturable (Km = 85 muM), non-concentrative, transport system for thymidine was demonstrated in Novikoff rat hepatoma cells depleted of ATP. At concentrations of thymidine less than the Km, this system operated at velocities sufficient to nearly completely equilibrate intra- and extra-cellular thymidine pools within 8 seconds. In phosphorylating cells, the transport system operated with similar rapidity, so that intracellular phosphorylation was rate-limiting for the incorporation of thymidine into nucleotides. Uptake of 3-O-methylglucose occurred at comparable velocities, attaining 90% of equilibrium between internal and external pools within 25 seconds. Uptake of cytosine by simple diffusion was 100 times slower."}
{"id": "PMID:188835", "title": "Hormonal regulation of amino acid transport and gluconeogenesis in primary cultures of adult rat liver parenchymal cells.", "content": "Amino acid transport was studied in primary cultures of parenchymal cells isolated from adult rat liver by a collagenase perfusion technique and maintained as a monolayer in a serum-free culture medium. These cells carried out gluconeogenesis from three carbon precursors (alanine, pyruvate, and lactate) in response to glucagon addition. Amino acid transport was assayed by measuring the uptake of the nonmetabolizable amino acid, alpha-aminoisobutyric acid (AIB). Addition of insulin or glucagon to culture rat liver parenchymal cells resulted in an increased influx of AIB transport. The glucocorticoid, dexamethasone, when added alone to cultures did not affect AIB transport. However, prior or simultaneous addition of dexamethasone to glucagon-treated cells caused a strong potentiation of the glucagon induction of AIB transport. Kinetic analysis of the effects of insulin and glucagon demonstrated that insulin increased the Vmax for transport without changing the Km while glucagon primarily decreased the Km for AIB transport. The effect of dexamethasone was to increase the Vmax of the low Km system.", "contents": "Hormonal regulation of amino acid transport and gluconeogenesis in primary cultures of adult rat liver parenchymal cells. Amino acid transport was studied in primary cultures of parenchymal cells isolated from adult rat liver by a collagenase perfusion technique and maintained as a monolayer in a serum-free culture medium. These cells carried out gluconeogenesis from three carbon precursors (alanine, pyruvate, and lactate) in response to glucagon addition. Amino acid transport was assayed by measuring the uptake of the nonmetabolizable amino acid, alpha-aminoisobutyric acid (AIB). Addition of insulin or glucagon to culture rat liver parenchymal cells resulted in an increased influx of AIB transport. The glucocorticoid, dexamethasone, when added alone to cultures did not affect AIB transport. However, prior or simultaneous addition of dexamethasone to glucagon-treated cells caused a strong potentiation of the glucagon induction of AIB transport. Kinetic analysis of the effects of insulin and glucagon demonstrated that insulin increased the Vmax for transport without changing the Km while glucagon primarily decreased the Km for AIB transport. The effect of dexamethasone was to increase the Vmax of the low Km system."}
{"id": "PMID:188836", "title": "Sodium: a regulator of glucose uptake in virus-transformed and nontransformed cells.", "content": "Observations of cells transformed by the Bryan strain of Rous sarcoma virus (RSV-BH) suggested that the intracellular concentrations of sodium ion (Na+) may play a critical role in cellular metabolism. In an attempt to manipulate intracellular Na+, chick embryo cells were exposed to graded concentrations of Na+ in the cellular growth medium, and the effects on capacity for glucose uptake was examined. After incubation for six hours, the incorporation rate of 2-deoxyglucose (used as a substitute for glucose) was proportional to the external Na+ concentration over the range, 100 mM to 200 mM. Cells transformed by RSV-BH were less responsive than nontransformed cells to differences in Na+ at low concentrations. The changes were specifically dependent upon Na+, since K+, Li+, or choline + were ineffective as substitutes, and increasing the ionic strength above that of 120 mM Na+ was effective only when Na+ was the added cation.", "contents": "Sodium: a regulator of glucose uptake in virus-transformed and nontransformed cells. Observations of cells transformed by the Bryan strain of Rous sarcoma virus (RSV-BH) suggested that the intracellular concentrations of sodium ion (Na+) may play a critical role in cellular metabolism. In an attempt to manipulate intracellular Na+, chick embryo cells were exposed to graded concentrations of Na+ in the cellular growth medium, and the effects on capacity for glucose uptake was examined. After incubation for six hours, the incorporation rate of 2-deoxyglucose (used as a substitute for glucose) was proportional to the external Na+ concentration over the range, 100 mM to 200 mM. Cells transformed by RSV-BH were less responsive than nontransformed cells to differences in Na+ at low concentrations. The changes were specifically dependent upon Na+, since K+, Li+, or choline + were ineffective as substitutes, and increasing the ionic strength above that of 120 mM Na+ was effective only when Na+ was the added cation."}
{"id": "PMID:188837", "title": "Derepression and carrier turnover: evidence for two distinct mechanisms of hexose transport regulation in animal cells.", "content": "Hexose uptake by hamster cells was increased five to ten fold by either substituting D-fructose for glucose or by completely omitting D-glucose from the culture medium for 24 to 48 hours. Conversely, when cycloheximide was present for 24 hours in media containing glucose, up to 20-fold decreases in hexose uptake were observed. However, these decreases in uptake activity were only observed over a narrow range of cycloheximide concentrations. After extended exposure to low concentrations of cycloheximide (0.05 to 10 mug/ml), the uptake by the fed cells decreased parallel with inhibition of protein synthesis whereas at high concentrations (greater than 50 mug/ml) uptake was increased. Cells deprived of glucose and maintained in the presence of cycloheximide did not show decreases in uptake activity. In separate experiments the high uptake rates of glucose-starved cells could be decreased by addition of glucose-free medium. The reversal was complete in 6 to 8 hours. The analog of glucose, 2-deoxy-D-glucose, did not promote the time-dependent decrease suggesting that the 6-phosphoester of glucose is not an inhibitor of transport. In addition, when cycloheximide is added at the same time as glucose, there is no decrease in uptake for at least 12 hours. We propose that turnover of components of hexose uptake systems could account for part of the control of hexose transport. Moreover, the results indicate that the turnover mechanism becomes inactive during glucose starvation and must be resynthetized following refeeding of the starved cells with glucose.", "contents": "Derepression and carrier turnover: evidence for two distinct mechanisms of hexose transport regulation in animal cells. Hexose uptake by hamster cells was increased five to ten fold by either substituting D-fructose for glucose or by completely omitting D-glucose from the culture medium for 24 to 48 hours. Conversely, when cycloheximide was present for 24 hours in media containing glucose, up to 20-fold decreases in hexose uptake were observed. However, these decreases in uptake activity were only observed over a narrow range of cycloheximide concentrations. After extended exposure to low concentrations of cycloheximide (0.05 to 10 mug/ml), the uptake by the fed cells decreased parallel with inhibition of protein synthesis whereas at high concentrations (greater than 50 mug/ml) uptake was increased. Cells deprived of glucose and maintained in the presence of cycloheximide did not show decreases in uptake activity. In separate experiments the high uptake rates of glucose-starved cells could be decreased by addition of glucose-free medium. The reversal was complete in 6 to 8 hours. The analog of glucose, 2-deoxy-D-glucose, did not promote the time-dependent decrease suggesting that the 6-phosphoester of glucose is not an inhibitor of transport. In addition, when cycloheximide is added at the same time as glucose, there is no decrease in uptake for at least 12 hours. We propose that turnover of components of hexose uptake systems could account for part of the control of hexose transport. Moreover, the results indicate that the turnover mechanism becomes inactive during glucose starvation and must be resynthetized following refeeding of the starved cells with glucose."}
{"id": "PMID:188838", "title": "Glucose transport and metabolism in cultured cells of nervous tissue.", "content": "The effect of the concentration of glucose in the medium on the intracellular concentrations of metabolites of C-6 astrocytoma cells and C-1300 neuroblastoma cells in culture has been investigated. The intracellular concentrations of glucose, glycogen, glucose 6-P and UDP-glucose were measured at intervals after feeding the cells. A rapid increase in glucose and glucose 6-P levels occurred when fresh medium containing 5.5 mM glucose was applied to the cells, followed by slower increases in UDP-glucose andglycogen. When the medium glucose was increased ten-fold, the intracellular concentration of glucose was increased, but the level of glucose 6-P, UDP=-glucose and glycogen were not altered, nor were the rates of accumulation. The addition of insulin to the medium resulted in an increase of intracellular glucose, glucose 6-P and glycogen. The transport of glucose into the cells is not the rate-limiting step of the regulation of metabolite levels in the cells.", "contents": "Glucose transport and metabolism in cultured cells of nervous tissue. The effect of the concentration of glucose in the medium on the intracellular concentrations of metabolites of C-6 astrocytoma cells and C-1300 neuroblastoma cells in culture has been investigated. The intracellular concentrations of glucose, glycogen, glucose 6-P and UDP-glucose were measured at intervals after feeding the cells. A rapid increase in glucose and glucose 6-P levels occurred when fresh medium containing 5.5 mM glucose was applied to the cells, followed by slower increases in UDP-glucose andglycogen. When the medium glucose was increased ten-fold, the intracellular concentration of glucose was increased, but the level of glucose 6-P, UDP=-glucose and glycogen were not altered, nor were the rates of accumulation. The addition of insulin to the medium resulted in an increase of intracellular glucose, glucose 6-P and glycogen. The transport of glucose into the cells is not the rate-limiting step of the regulation of metabolite levels in the cells."}
{"id": "PMID:188839", "title": "Transport as a rate limiting step in glucose metabolism in virus-transformed cells: studies with cytochalasin B.", "content": "Steady-state kinetic tracer analysis and two-dimensional chromatography and autoradiography were used to examine the relation of glucose transport to its metabolism in cultured chick embryo fibroblasts. Cytochalasin B was added to Rous sarcoma virus-infected cells to bring the rate of glucose uptake to the level of uninfected cells. It is concluded for chick cells in culture that: (1) the transport of glucose, rather than its phosphorylation, is the rate limiting step and (2) the difference in aerobic glycolysis between normal and virus-transformed cells at physiological glucose concentration may be a consequence  of the difference in the rates of glucose uptake.", "contents": "Transport as a rate limiting step in glucose metabolism in virus-transformed cells: studies with cytochalasin B. Steady-state kinetic tracer analysis and two-dimensional chromatography and autoradiography were used to examine the relation of glucose transport to its metabolism in cultured chick embryo fibroblasts. Cytochalasin B was added to Rous sarcoma virus-infected cells to bring the rate of glucose uptake to the level of uninfected cells. It is concluded for chick cells in culture that: (1) the transport of glucose, rather than its phosphorylation, is the rate limiting step and (2) the difference in aerobic glycolysis between normal and virus-transformed cells at physiological glucose concentration may be a consequence  of the difference in the rates of glucose uptake."}
{"id": "PMID:188840", "title": "Transport changes associated with growth control and malignant transformation.", "content": "We can distinguish two classes of membrane transport changes in cultured cells: (a) growth-rate contingent changes are those which occur in coordination with the onset of density-dependent inhibition of growth; (b) transformation-specific changes are those which occur when cells become transformed, and which can be detected even when normal and transformed cells are growing at the same rate. Growth-rate contingent changes include the density-dependent changes in phosphate, nucleoside, glucose, amino acid, and potassium transport. Only one transformation-specific transport change has been found in Rous-transformed chicken embryo fibroblasts: an increased rate of hexose transport. The variation in potassium transport are associated with variations in the number of ouabain binding sites in the membrane. The molecular basis for changes in the rate of hexose transport is unknown, although gross changes in membrane bilayer composition and \"fluidity\" seem not to be involved. In analyzing the regulation of hexose transport activity, we find that decreased cAMP may play a role in the transformation-specific increase in hexose transport, but that fibrinolytic activity is not necessary.", "contents": "Transport changes associated with growth control and malignant transformation. We can distinguish two classes of membrane transport changes in cultured cells: (a) growth-rate contingent changes are those which occur in coordination with the onset of density-dependent inhibition of growth; (b) transformation-specific changes are those which occur when cells become transformed, and which can be detected even when normal and transformed cells are growing at the same rate. Growth-rate contingent changes include the density-dependent changes in phosphate, nucleoside, glucose, amino acid, and potassium transport. Only one transformation-specific transport change has been found in Rous-transformed chicken embryo fibroblasts: an increased rate of hexose transport. The variation in potassium transport are associated with variations in the number of ouabain binding sites in the membrane. The molecular basis for changes in the rate of hexose transport is unknown, although gross changes in membrane bilayer composition and \"fluidity\" seem not to be involved. In analyzing the regulation of hexose transport activity, we find that decreased cAMP may play a role in the transformation-specific increase in hexose transport, but that fibrinolytic activity is not necessary."}
{"id": "PMID:188841", "title": "Regulation of sugar transport in chick embryo fibroblasts and in fibroblasts transformed by a temperature-sensitive mutant of the Rous sarcoma virus.", "content": "The mode of induction of sugar transport by serum-stimulation of growth and hexose-starvation in chick embryo fibroblasts (CEF) has been studied using metabolic inhibitors. We have concluded from these studies that the sugar transport increases induced by serum-stimulation are regulated by post-transcriptional mechanisms while sugar transport increases induced by hexose-starvation are regulated by a transcriptional mechanism. CEF infected with a temperature-sensitive mutant of the Rous sarcoma virus. Ts68 and incubated at the nonpermissive temperature for transformation, 41 degrees, retain the capacity to regulate sugar transport in a manner similar to uninfected CEF. However, Ts68-infected CEF maintained at the permissive temperature for transformation, 37 degrees, have lost the ability to regulate sugar transport at the post-transcriptional and post-translational levels.", "contents": "Regulation of sugar transport in chick embryo fibroblasts and in fibroblasts transformed by a temperature-sensitive mutant of the Rous sarcoma virus. The mode of induction of sugar transport by serum-stimulation of growth and hexose-starvation in chick embryo fibroblasts (CEF) has been studied using metabolic inhibitors. We have concluded from these studies that the sugar transport increases induced by serum-stimulation are regulated by post-transcriptional mechanisms while sugar transport increases induced by hexose-starvation are regulated by a transcriptional mechanism. CEF infected with a temperature-sensitive mutant of the Rous sarcoma virus. Ts68 and incubated at the nonpermissive temperature for transformation, 41 degrees, retain the capacity to regulate sugar transport in a manner similar to uninfected CEF. However, Ts68-infected CEF maintained at the permissive temperature for transformation, 37 degrees, have lost the ability to regulate sugar transport at the post-transcriptional and post-translational levels."}
{"id": "PMID:188842", "title": "Loss of the post-translational control of nutrient transport in vitro and in vivo virus-transformed chicken cells.", "content": "The removal of serum from the medium of uninfected fibroblasts decreased the rate of uptake of uridine, 2-deoxyglucose, alpha-aminoisobutyrate and thymidine. Its subsequent addition rapidly and reversibly stimulated the uptake of all the nutrients but thymidine and this response was not inhibited by treatment of the cells with cycloheximide. The cycloheximide insensitive, rapid increase in the rate of transport has been designated post-translational control. The nutrient transport systems in chick embryo fibroblasts transformed in vitro with avian sarcoma viruses and virus-induced cultured chicken tumor cells do not respond to serum removal or addition. Two possible levels for the control of nutrient transport, i.e., mitogen receptor occupancy and mitrogen-induced activation of the transport system, are presented to explain these observations.", "contents": "Loss of the post-translational control of nutrient transport in vitro and in vivo virus-transformed chicken cells. The removal of serum from the medium of uninfected fibroblasts decreased the rate of uptake of uridine, 2-deoxyglucose, alpha-aminoisobutyrate and thymidine. Its subsequent addition rapidly and reversibly stimulated the uptake of all the nutrients but thymidine and this response was not inhibited by treatment of the cells with cycloheximide. The cycloheximide insensitive, rapid increase in the rate of transport has been designated post-translational control. The nutrient transport systems in chick embryo fibroblasts transformed in vitro with avian sarcoma viruses and virus-induced cultured chicken tumor cells do not respond to serum removal or addition. Two possible levels for the control of nutrient transport, i.e., mitogen receptor occupancy and mitrogen-induced activation of the transport system, are presented to explain these observations."}
{"id": "PMID:188843", "title": "Is glucose transport enhanced in virus-transformed mammalian cells? A dissenting view.", "content": "Much of the literature on the uptake of glucose by untransformed and transformed animal cells is based on experiments carried out with 2-deoxy-D-glucose (2-DOG). Results obtained with this analog can be ambiguous, since 2-DOG can be phosphorylated by hexokinases of animal cells. An intracellular trapping mechanism is thus provided. Therefore, the total flux of 2-DOG into the cell is a resultant of both transport and hexokinase action, and the measurement of total 2-DOG incorporation is a valid measurement of transport only if 2-DOG is phosphorylated as rapidly as it enters the cell. Evidence is presented here that this is not necessarily the case, significant levels of free intracellular 2-DOG approaching external concentrations were found in untransformed and transformed mouse 3T3 cells even at early times during uptake. Differences in total intracellular 2-DOG between untransformed and transformed cells were accounted for entirely by 2-deoxyglucose phosphate. Thus, it appears the apparent increase of 2-DOG uptake accompanying transformation in these cell lines is not due to an effect on the transport process, but on enhanced phosphorylation, which is a reflection of an alteration in the regulation of glycolysis. The ambiguity introduced by phosphorylation can be oviated by the use of an analog that cannot be phosphorylated, such as 3-O-methyl-D-glucose. The rate of transport and efflux of this sugar was not found to be different in untransformed versus transformed 3T3 cells. Moreover, deficiencies of this analog as a substrate for the glucose transport system are pointed out.", "contents": "Is glucose transport enhanced in virus-transformed mammalian cells? A dissenting view. Much of the literature on the uptake of glucose by untransformed and transformed animal cells is based on experiments carried out with 2-deoxy-D-glucose (2-DOG). Results obtained with this analog can be ambiguous, since 2-DOG can be phosphorylated by hexokinases of animal cells. An intracellular trapping mechanism is thus provided. Therefore, the total flux of 2-DOG into the cell is a resultant of both transport and hexokinase action, and the measurement of total 2-DOG incorporation is a valid measurement of transport only if 2-DOG is phosphorylated as rapidly as it enters the cell. Evidence is presented here that this is not necessarily the case, significant levels of free intracellular 2-DOG approaching external concentrations were found in untransformed and transformed mouse 3T3 cells even at early times during uptake. Differences in total intracellular 2-DOG between untransformed and transformed cells were accounted for entirely by 2-deoxyglucose phosphate. Thus, it appears the apparent increase of 2-DOG uptake accompanying transformation in these cell lines is not due to an effect on the transport process, but on enhanced phosphorylation, which is a reflection of an alteration in the regulation of glycolysis. The ambiguity introduced by phosphorylation can be oviated by the use of an analog that cannot be phosphorylated, such as 3-O-methyl-D-glucose. The rate of transport and efflux of this sugar was not found to be different in untransformed versus transformed 3T3 cells. Moreover, deficiencies of this analog as a substrate for the glucose transport system are pointed out."}
{"id": "PMID:188844", "title": "Saturable and nonsaturable process of sugar uptake: effect of oncogenic transformation in transport and uptake of nutrients.", "content": "Uptake of sugars into cells by a saturable process increased enormously during and after transformation, and uptake by a nonsaturable process increased significantly but less remarkably compared to controls. The drastic change of uptake rates, observed at around 5 x 10(-3) M sugar during and after transformation, emphasizes the significant observation that transition of the sugar uptake system from a saturable to a nonsaturable process occurs near the physiological concentration of D-glucose normally seen in animal blood. At concentrations below higher than 5 x 10(-3) M, where a saturable process is barely involved, nonsaturable uptakes of D-glucose, D-mannose, D-galactose, 2-deoxy-D-glucose and 3-O-methyl-D-glucose proceed tens to hundreds fold faster than the rate of simple diffusion of L-glucose. These findings suggest that nonsaturable uptake of the sugars known to be substrates for the saturable transport carrier system may not be a physical process or simple diffusion, as observed for L-glucose uptake. Rather, the nonsaturable uptake might be part of the total physiological process which, along with the saturable process, is controlled by a membrane-coordination mechanism. A plausible mechanism is discussed in which negative cooperativity of nutrient uptake, such as that found in bacteria, is involved.", "contents": "Saturable and nonsaturable process of sugar uptake: effect of oncogenic transformation in transport and uptake of nutrients. Uptake of sugars into cells by a saturable process increased enormously during and after transformation, and uptake by a nonsaturable process increased significantly but less remarkably compared to controls. The drastic change of uptake rates, observed at around 5 x 10(-3) M sugar during and after transformation, emphasizes the significant observation that transition of the sugar uptake system from a saturable to a nonsaturable process occurs near the physiological concentration of D-glucose normally seen in animal blood. At concentrations below higher than 5 x 10(-3) M, where a saturable process is barely involved, nonsaturable uptakes of D-glucose, D-mannose, D-galactose, 2-deoxy-D-glucose and 3-O-methyl-D-glucose proceed tens to hundreds fold faster than the rate of simple diffusion of L-glucose. These findings suggest that nonsaturable uptake of the sugars known to be substrates for the saturable transport carrier system may not be a physical process or simple diffusion, as observed for L-glucose uptake. Rather, the nonsaturable uptake might be part of the total physiological process which, along with the saturable process, is controlled by a membrane-coordination mechanism. A plausible mechanism is discussed in which negative cooperativity of nutrient uptake, such as that found in bacteria, is involved."}
{"id": "PMID:188845", "title": "High-affinity cytochalasin B binding to normal and transformed BALB/3T3 cells.", "content": "To study the molecular basis of changes in sugar uptake rate in cultured mouse fibroblasts with different physiological states, we have measured the high affinity binding of [3H] cytochalsin B, a potent sugar transport inhibitor, to actively growing and contact inhibited Balb/3T3 cells as well as to 3T12 and SV3T3 cells. Binding was the same whether the cells were detached from dishes with EDTA or trypsin. The amount of drug bound to intact cells measured with a centrifugation assay was essentially the same as that bound to cell sonicates measured with equilibrium dialysis. Cytochalasin B binding to intact cells was extremely rapid and reversible over a wide range of drug concentrations, and was not affected by 0.1 M D--glucose in the assay medium. Actively growing and contact inhibited 3T3 cells had a similar number of high affinity cytochalasin B binding sites per cell, while 3T12 and SV3T3 cells had one third to one fourth the number of sites per cell. However, the number of sites per mug cellular protein appeared to be similar for cells in all of the physiological states examined.", "contents": "High-affinity cytochalasin B binding to normal and transformed BALB/3T3 cells. To study the molecular basis of changes in sugar uptake rate in cultured mouse fibroblasts with different physiological states, we have measured the high affinity binding of [3H] cytochalsin B, a potent sugar transport inhibitor, to actively growing and contact inhibited Balb/3T3 cells as well as to 3T12 and SV3T3 cells. Binding was the same whether the cells were detached from dishes with EDTA or trypsin. The amount of drug bound to intact cells measured with a centrifugation assay was essentially the same as that bound to cell sonicates measured with equilibrium dialysis. Cytochalasin B binding to intact cells was extremely rapid and reversible over a wide range of drug concentrations, and was not affected by 0.1 M D--glucose in the assay medium. Actively growing and contact inhibited 3T3 cells had a similar number of high affinity cytochalasin B binding sites per cell, while 3T12 and SV3T3 cells had one third to one fourth the number of sites per cell. However, the number of sites per mug cellular protein appeared to be similar for cells in all of the physiological states examined."}
{"id": "PMID:188846", "title": "Neoplastic potentials and regulation of uptake of nutrients. I. A glutamine independent variant of polyoma BHK with A very high neoplastic potential.", "content": "A variant of polyoma BHK cells is described which is capable of growing in a glutamine-free medium. These glutamine-independent variant cells (GIV) have a size and morphologic appearance intermediate between the nontransformed (BHK) and polyoma transformed (Py6) cell line. In contrast to Py6, the GIV cells grow more slowly, produce less lactic acid and do not grow in suspension. However, their adherence to substrate and release of galactosyltransferase into the medium is comparable to that seen with the parent PyBHK. Most striking is the finding that GIV cells are more readily agglutinated by Concanavalin A and when inoculated into hamsters are much more tumorigenic than the parent Py6 cells.", "contents": "Neoplastic potentials and regulation of uptake of nutrients. I. A glutamine independent variant of polyoma BHK with A very high neoplastic potential. A variant of polyoma BHK cells is described which is capable of growing in a glutamine-free medium. These glutamine-independent variant cells (GIV) have a size and morphologic appearance intermediate between the nontransformed (BHK) and polyoma transformed (Py6) cell line. In contrast to Py6, the GIV cells grow more slowly, produce less lactic acid and do not grow in suspension. However, their adherence to substrate and release of galactosyltransferase into the medium is comparable to that seen with the parent PyBHK. Most striking is the finding that GIV cells are more readily agglutinated by Concanavalin A and when inoculated into hamsters are much more tumorigenic than the parent Py6 cells."}
{"id": "PMID:188848", "title": "Regulation of amino acid and glucose transport activity expressed in isolated membranes from untransformed and SV 40-transformed mouse fibroblasts.", "content": "Membrane vesicles isolated from untransformed Balb/c and Swiss mouse fibroblasts and their SV 40-transformed derivatives were shown to catalyze carrier-mediated, intravesicular uptake of alpha-aminoisobutyric acid and D-glucose. Concentrative uptake of alpha-aminoisobutyric acid required the presence of a Na+-gradient (external greater than internal) and could occur independently of endogenous (Na+ + K+)ATPase activity. A K+ diffusion gradient (internal greater than external) in the presence of valinomycin, or the addition of the Na+ salt of a highly permeant anion, conditions expected to create an interior-negative membrane potential stimulated Na+-gradient-dependent uptake, suggesting this process is electrogenic. D-Glucose uptake was nonconcentrative and did not require ion gradients or metabolic conversion. Na+ gradient-dependent transport of alpha-aminoisobutyric acid was reduced both in initial rate and extent of uptake in vesicles from confluent untransformed cells and increased in those from SV 40-transformed cells, compared with activities observed in vesicles from proliferating untransformed cells. No changes in D-glucose carrier activity were observed when assayed at low glucose concentrations.", "contents": "Regulation of amino acid and glucose transport activity expressed in isolated membranes from untransformed and SV 40-transformed mouse fibroblasts. Membrane vesicles isolated from untransformed Balb/c and Swiss mouse fibroblasts and their SV 40-transformed derivatives were shown to catalyze carrier-mediated, intravesicular uptake of alpha-aminoisobutyric acid and D-glucose. Concentrative uptake of alpha-aminoisobutyric acid required the presence of a Na+-gradient (external greater than internal) and could occur independently of endogenous (Na+ + K+)ATPase activity. A K+ diffusion gradient (internal greater than external) in the presence of valinomycin, or the addition of the Na+ salt of a highly permeant anion, conditions expected to create an interior-negative membrane potential stimulated Na+-gradient-dependent uptake, suggesting this process is electrogenic. D-Glucose uptake was nonconcentrative and did not require ion gradients or metabolic conversion. Na+ gradient-dependent transport of alpha-aminoisobutyric acid was reduced both in initial rate and extent of uptake in vesicles from confluent untransformed cells and increased in those from SV 40-transformed cells, compared with activities observed in vesicles from proliferating untransformed cells. No changes in D-glucose carrier activity were observed when assayed at low glucose concentrations."}
{"id": "PMID:188849", "title": "[Amino acid transport by membrane vesicles of virally transformed and nontransformed cells: effects of sodium gradient and cell density].", "content": "Mixed membrane vesicle populations composed of plasma membrane and endoplasmic reticulum were prepared from Balb/c 3T3 and simian virus 40-transformed Balb/c 3T3 mouse fibroblasts. The initial rates of uptake of L-leucine and alpha-aminoisobutyric acid by these vesicles were stimulated by a NaCl gradient (external greater than internal). Cation specificity for stimulation of L-leucine uptake was Na+ greater than Li+ greater than K+. NaSCN was as effective as NaCl. Stimulation of uptake of both amino acids by a NaCl gradient was twice as great in vesicles from transformed as compared to non-transformed cells. The NaCl gradient produced transient accumulation of both L-leucine and alpha-aminoisobutyric acid to twice the equilibrium level in vesicles from transformed cells. No such \"overshoot\" was observed in vesicles from nontransformed cells. In vesicles from the contact-inhibitable Balb/c 3T3 cells, transport of alpha-aminoisobutyric acid, but non L-leucine, exhibited a density-dependent decrease in Na+ gradient induced stimulation, from 248% for sub-confluent to 109% with confluent cells. No density-related changes in uptake were noted with vesicles from the transformed cells. These studies suggest that variation in amino acid uptake associated with viral transformation may be related, at least in part, to alterations in Na+ permeability of the surface membrane.", "contents": "[Amino acid transport by membrane vesicles of virally transformed and nontransformed cells: effects of sodium gradient and cell density]. Mixed membrane vesicle populations composed of plasma membrane and endoplasmic reticulum were prepared from Balb/c 3T3 and simian virus 40-transformed Balb/c 3T3 mouse fibroblasts. The initial rates of uptake of L-leucine and alpha-aminoisobutyric acid by these vesicles were stimulated by a NaCl gradient (external greater than internal). Cation specificity for stimulation of L-leucine uptake was Na+ greater than Li+ greater than K+. NaSCN was as effective as NaCl. Stimulation of uptake of both amino acids by a NaCl gradient was twice as great in vesicles from transformed as compared to non-transformed cells. The NaCl gradient produced transient accumulation of both L-leucine and alpha-aminoisobutyric acid to twice the equilibrium level in vesicles from transformed cells. No such \"overshoot\" was observed in vesicles from nontransformed cells. In vesicles from the contact-inhibitable Balb/c 3T3 cells, transport of alpha-aminoisobutyric acid, but non L-leucine, exhibited a density-dependent decrease in Na+ gradient induced stimulation, from 248% for sub-confluent to 109% with confluent cells. No density-related changes in uptake were noted with vesicles from the transformed cells. These studies suggest that variation in amino acid uptake associated with viral transformation may be related, at least in part, to alterations in Na+ permeability of the surface membrane."}
{"id": "PMID:188850", "title": "Uptake of alpha-aminoisobutyric acid and phosphate by membrane vesicles derived from growing and quiescent fibroblasts.", "content": "Membrane vesicles derived principally from the plasma membrane and endoplasmic reticulum of mouse 3T3 cells transformed by Simian virus 40 take up alpha-aminoisobutyric acid (AIB) and phosphate (Pi). When NaCl is added simultaneously with AIB or Pi, uptake rises two- to three-times above the equilibrium to accumulate AIB or Pi over the control value, in the presence of a Na+ gradient, is almost lost in membrane vesicles derived from benzpyrene-transformed 3T3 cells (BP3T3) arrested in the G1 phase of the cell cycle by serum starvation. When added to the membranes with NaCl and the uptake substrate, a combination of fibroblast growth factor (FGF) and epidermal growth factor EGF restores the ability of the membranes to accumulate AIB and Pi over the control value.", "contents": "Uptake of alpha-aminoisobutyric acid and phosphate by membrane vesicles derived from growing and quiescent fibroblasts. Membrane vesicles derived principally from the plasma membrane and endoplasmic reticulum of mouse 3T3 cells transformed by Simian virus 40 take up alpha-aminoisobutyric acid (AIB) and phosphate (Pi). When NaCl is added simultaneously with AIB or Pi, uptake rises two- to three-times above the equilibrium to accumulate AIB or Pi over the control value, in the presence of a Na+ gradient, is almost lost in membrane vesicles derived from benzpyrene-transformed 3T3 cells (BP3T3) arrested in the G1 phase of the cell cycle by serum starvation. When added to the membranes with NaCl and the uptake substrate, a combination of fibroblast growth factor (FGF) and epidermal growth factor EGF restores the ability of the membranes to accumulate AIB and Pi over the control value."}
{"id": "PMID:188851", "title": "Regulation of plasma membrane protein phosphorylation in two mammalian cell types.", "content": "The appreciation of protein phosphorylation as a ubiquitous mechanism for the post-translational control of protein function has drawn our attention to the phosphorylation of plasma membrane proteins. We have studied this phenomenon in the human erythrocyte and rat adipocyte, and have observed several features, common to the two systems, which may be of general significance. In examining protein phosphorylation in intact cells incubated with 32Pi, it is evident that the 32P-polypeptides of the plasma membrane are among the most highly labelled species in the cell, despite their minor contribution to overall protein content. The addition of epinephrine (to adipocytes) or cAMP (to erythrocytes) increases the phosphorylation of certain peptides, whereas others are unaffected. The protein kinases mediating these phosphorylations are present in the plasma membrane as isolated, and can be divided into two groups--cAMP dependent and cAMP independent. These two classes of kinase differ markedly in their substrate specificity toward endogenous and exogenous polypeptide substrates. Two classes of protein kinases with similar properties can be detected in the cytoplasm. The relationship between the membrane-bound and cytoplasmic enzymes is uncertain. The potential roles of the plasma membrane cAMP dependent protein kinases are evident from the diverse effects of cAMP on surface properties; however, the prevalence of plasma membrane proteins phosphorylated via cAMP independent pathways is striking. Thus, elucidation of the regulatory properties of the plasma membrane cAMP independent protein kinases may give new insight into the control of a variety of surface phenomena not mediated by cAMP.", "contents": "Regulation of plasma membrane protein phosphorylation in two mammalian cell types. The appreciation of protein phosphorylation as a ubiquitous mechanism for the post-translational control of protein function has drawn our attention to the phosphorylation of plasma membrane proteins. We have studied this phenomenon in the human erythrocyte and rat adipocyte, and have observed several features, common to the two systems, which may be of general significance. In examining protein phosphorylation in intact cells incubated with 32Pi, it is evident that the 32P-polypeptides of the plasma membrane are among the most highly labelled species in the cell, despite their minor contribution to overall protein content. The addition of epinephrine (to adipocytes) or cAMP (to erythrocytes) increases the phosphorylation of certain peptides, whereas others are unaffected. The protein kinases mediating these phosphorylations are present in the plasma membrane as isolated, and can be divided into two groups--cAMP dependent and cAMP independent. These two classes of kinase differ markedly in their substrate specificity toward endogenous and exogenous polypeptide substrates. Two classes of protein kinases with similar properties can be detected in the cytoplasm. The relationship between the membrane-bound and cytoplasmic enzymes is uncertain. The potential roles of the plasma membrane cAMP dependent protein kinases are evident from the diverse effects of cAMP on surface properties; however, the prevalence of plasma membrane proteins phosphorylated via cAMP independent pathways is striking. Thus, elucidation of the regulatory properties of the plasma membrane cAMP independent protein kinases may give new insight into the control of a variety of surface phenomena not mediated by cAMP."}
{"id": "PMID:188853", "title": "Phosphohydrolases on the cell surface of BHK cells: loss during long term culture.", "content": "Low passage BHK 21/13 cells contain two cell surface enzymes, a nucleotide pyrophosphatase and a monophosphoester hydrolase, which together hydrolyze exogenous UDP-galactose to free galactose. During serial passage, BHK cells successively lose both enzymes. Concomitant with the loss of these enzymatic activities, changes in cell morphology, as well as in the serum requirement for the initiation of DNA synthesis, were observed. Clonal sublines of BHK cells were isolated, which differed qualitatively in their ability to hydrolyze UDP-galactose. Clonal BHK sublines, which exhibited both enzymatic activities on their cell surface, resembled low passage BHK cells in morphology and serum requirement for the initiation of DNA synthesis. Sublines not containing these enzymes resembled BHK cells of high passage cultures. The ability of intact BHK cells to hydrolyze exogenous nucleotide sugars may serve as an indicator for the progression of BHK cells from a normal to a more transformed state.", "contents": "Phosphohydrolases on the cell surface of BHK cells: loss during long term culture. Low passage BHK 21/13 cells contain two cell surface enzymes, a nucleotide pyrophosphatase and a monophosphoester hydrolase, which together hydrolyze exogenous UDP-galactose to free galactose. During serial passage, BHK cells successively lose both enzymes. Concomitant with the loss of these enzymatic activities, changes in cell morphology, as well as in the serum requirement for the initiation of DNA synthesis, were observed. Clonal sublines of BHK cells were isolated, which differed qualitatively in their ability to hydrolyze UDP-galactose. Clonal BHK sublines, which exhibited both enzymatic activities on their cell surface, resembled low passage BHK cells in morphology and serum requirement for the initiation of DNA synthesis. Sublines not containing these enzymes resembled BHK cells of high passage cultures. The ability of intact BHK cells to hydrolyze exogenous nucleotide sugars may serve as an indicator for the progression of BHK cells from a normal to a more transformed state."}
{"id": "PMID:188856", "title": "[Large non-secreting islet cell adenomas. Review of the literature].", "content": "The authors report a case of benign non secretory islet cell tumour. Ten other cases of this type were found in the literature. These non-functional tumours \u00e9volve without symptoms and are rarely diagnosed in the presence of an abdominal mass. They are usually discovered at autopsy. Clinical examination and further investigation do not always demonstrate the pancreatic origin of the tumour observed. Treatment is surgical consisting of removal of the tumour. Pathological examination leads to the diagnosis of non-secretory islet cell tumour which is usually benign; only the course can confirm this.", "contents": "[Large non-secreting islet cell adenomas. Review of the literature]. The authors report a case of benign non secretory islet cell tumour. Ten other cases of this type were found in the literature. These non-functional tumours \u00e9volve without symptoms and are rarely diagnosed in the presence of an abdominal mass. They are usually discovered at autopsy. Clinical examination and further investigation do not always demonstrate the pancreatic origin of the tumour observed. Treatment is surgical consisting of removal of the tumour. Pathological examination leads to the diagnosis of non-secretory islet cell tumour which is usually benign; only the course can confirm this."}
{"id": "PMID:188857", "title": "Preparation of plates with a permanent adsorbent layer and their application in the analytical thin-layer chromatography of lipids.", "content": "Experimental conditions for preparing the thin-layer chromatographic plates with a permanent adsorbent layer (PAL) have been established; the particles of this layer are firmly bound to each other and to the glass support by means of fused glass powder. To prepare the PAL plates, a mixture of Woelm silica gel and glass powder (1:3, w/w) of particle size 7+/-1 mum was suspended in toluene and spread on the plates, yielding PALs of thickens 150-250 mum. The plates were heated in an electric furnace at 675 degrees for 20 min. In the separation of neutral lipids, a PAL thus prepared is equal in efficiency and selectivity to silica gel layers prepared in the usual manner.", "contents": "Preparation of plates with a permanent adsorbent layer and their application in the analytical thin-layer chromatography of lipids. Experimental conditions for preparing the thin-layer chromatographic plates with a permanent adsorbent layer (PAL) have been established; the particles of this layer are firmly bound to each other and to the glass support by means of fused glass powder. To prepare the PAL plates, a mixture of Woelm silica gel and glass powder (1:3, w/w) of particle size 7+/-1 mum was suspended in toluene and spread on the plates, yielding PALs of thickens 150-250 mum. The plates were heated in an electric furnace at 675 degrees for 20 min. In the separation of neutral lipids, a PAL thus prepared is equal in efficiency and selectivity to silica gel layers prepared in the usual manner."}
{"id": "PMID:188858", "title": "The van urk-Salkowski reagent--a sensitive and specific chromogenic reagent for silica gel thin-layer chromatographic detection and identification of indole derivatives.", "content": "The chromogenic reagent described has been tested with seventy-nine indole derivatives and found to be very sensitive and indole-specific. The lower limit of detection on silica gel thin-layer plates was between 25 and 50 ng for most indoles. Phenols and hydroxy-, and amino-benzoic acids, hydroxy-, and methoxy-cinnamic acids did not yield chromophores with the exception of p-amino-benzoic acid and p-hydroxy-cinnamic acid which gave yellow and pink chromophores at concentrations greater than 1 and 2 mug. Although many of the C-3 substituted indoles such as indole-3-acetic acid and tryptamine had colors in the reddish-violet-blue color region, most exhibited sufficient color differentiation to allow their identification by thin-layer chromatography. The procedure was simple and required only 10 min from the time of spraying the thin-layer plate until full color development was reached. The colors had a wide spectral range from yellow of the indole-3-glyoxylamide chromophore to blue of the melatonin chromophore, and were extremely stable.", "contents": "The van urk-Salkowski reagent--a sensitive and specific chromogenic reagent for silica gel thin-layer chromatographic detection and identification of indole derivatives. The chromogenic reagent described has been tested with seventy-nine indole derivatives and found to be very sensitive and indole-specific. The lower limit of detection on silica gel thin-layer plates was between 25 and 50 ng for most indoles. Phenols and hydroxy-, and amino-benzoic acids, hydroxy-, and methoxy-cinnamic acids did not yield chromophores with the exception of p-amino-benzoic acid and p-hydroxy-cinnamic acid which gave yellow and pink chromophores at concentrations greater than 1 and 2 mug. Although many of the C-3 substituted indoles such as indole-3-acetic acid and tryptamine had colors in the reddish-violet-blue color region, most exhibited sufficient color differentiation to allow their identification by thin-layer chromatography. The procedure was simple and required only 10 min from the time of spraying the thin-layer plate until full color development was reached. The colors had a wide spectral range from yellow of the indole-3-glyoxylamide chromophore to blue of the melatonin chromophore, and were extremely stable."}
{"id": "PMID:188859", "title": "Adriamycin therapy for advanced insulinoma.", "content": "Two patients with advanced metastatic insulinoma are presented. Both failed to respond to streptozotocin and were refractory to other forms of chemotherapy. Therapy with adriamycin (Patient No. 1) and adriamycin plus 5-fluorouracil (Patient No. 2) led to significant decreases in insulin levels or measurable disease and both patients had clinical remissions lasting 5 to 7 months. Adriamycin may be effective in patients with advanced insulinoma unresponsive to conventional chemotherapy.", "contents": "Adriamycin therapy for advanced insulinoma. Two patients with advanced metastatic insulinoma are presented. Both failed to respond to streptozotocin and were refractory to other forms of chemotherapy. Therapy with adriamycin (Patient No. 1) and adriamycin plus 5-fluorouracil (Patient No. 2) led to significant decreases in insulin levels or measurable disease and both patients had clinical remissions lasting 5 to 7 months. Adriamycin may be effective in patients with advanced insulinoma unresponsive to conventional chemotherapy."}
{"id": "PMID:188860", "title": "High molecular weight forms of human ACTH are glycoproteins.", "content": "The RIA-ACTH in a normal human pituitary, 2 ectopic ACTH-secreting tumors and plasma from a patient with Nelson's syndrome and one with ectopic ACTH syndrome was divided into 3 molecular weight classes after gel exclusion chromatography. The largest component appeared in or near the void volume and was designated \"big\" RIA-ACTH. The second, designated \"intermediate\" RIA-ACTH, eluted between the void volume and standard human 1-39 ACTH (mol. wt. 4,541). An immunoreactive material designated \"little\" ACTH-coeluted with standard human ACTH. A significant fraction (29-61%) of \"big\" RIA-ACTH from the tumors bound to concanavalin A-agarose and was eluted with 0.2 M alpha-methyl-D-mannopyranoside. An additional 16-22% of \"big\" RIA-ACTH was more tightly bound to the concanavalin A, but could be purged from the column with 0.1 M acetic acid. A smaller total percent of \"big\" RIA-ACTH from the pituitary (20%) and plasmas (5-10%) bound to the lectin and was similarly eluted and purged. Relatively little (less than 8%) of \"intermediate\" RIA-ACTH from all sources bound to concanavalin A, with the exception of that in the pitull sources was essentially excluded (greater than 93%) from the column. These data indicate that a significant fraction of human \"big\" RIA-ACTH is a glycoprotein and that human \"intermediate\" RIA-ACTH may be also.", "contents": "High molecular weight forms of human ACTH are glycoproteins. The RIA-ACTH in a normal human pituitary, 2 ectopic ACTH-secreting tumors and plasma from a patient with Nelson's syndrome and one with ectopic ACTH syndrome was divided into 3 molecular weight classes after gel exclusion chromatography. The largest component appeared in or near the void volume and was designated \"big\" RIA-ACTH. The second, designated \"intermediate\" RIA-ACTH, eluted between the void volume and standard human 1-39 ACTH (mol. wt. 4,541). An immunoreactive material designated \"little\" ACTH-coeluted with standard human ACTH. A significant fraction (29-61%) of \"big\" RIA-ACTH from the tumors bound to concanavalin A-agarose and was eluted with 0.2 M alpha-methyl-D-mannopyranoside. An additional 16-22% of \"big\" RIA-ACTH was more tightly bound to the concanavalin A, but could be purged from the column with 0.1 M acetic acid. A smaller total percent of \"big\" RIA-ACTH from the pituitary (20%) and plasmas (5-10%) bound to the lectin and was similarly eluted and purged. Relatively little (less than 8%) of \"intermediate\" RIA-ACTH from all sources bound to concanavalin A, with the exception of that in the pitull sources was essentially excluded (greater than 93%) from the column. These data indicate that a significant fraction of human \"big\" RIA-ACTH is a glycoprotein and that human \"intermediate\" RIA-ACTH may be also."}
{"id": "PMID:188861", "title": "Collaborative study of the effects of human growth hormone in growth hormone deficiency: IV. Treatment with low doses of human growth hormone based on body weight.", "content": "In order to define the minimum effective dose of human growth hormone (GH) in growth hormone deficient children, GH was administered to three groups of patients based on their body weight. Five children who received 0.01 International Unit (IU) GH/kg three times a week (tiw) failed to respond with a significant increase in their rate of growth. A dose of 0.03 IU GH/kg tiw increased the growth rate of 12 patients from 3.5 +/- 0.4 (SE) cm/year to 6.4 +/- 0.4 (SE) cm/year (P less than 0.001) during the first 12 months of therapy. Eight children (67%) larger than or equal to 6.0 cm/year. A similar increase growth rate from 3.6 +/- 0.4 (SE) cm/year to 7.3 +/- 0.4 (SE) cm/year (P less than 0.001) was observed over the first 12 months of therapy in 16 growth hormone deficient children who were given 0.06 IU GH/kg tiw. Thirteen children (81%) grew larger than or equal to 6.0 cm/year. During a second year of treatment, children receiving either 0.03 or 0.06 UI GH/kg tiw again showed a significant increase in their rate of growth. However, the response was significantly less than that observed during the first year of treatment. Comparison of these results with those available in the literature suggests that the most efficient, although not necessarily the optimal, initial dose of GH in children with growth hormone deficiency is 0.06 IU GH/kg administered three times a week.", "contents": "Collaborative study of the effects of human growth hormone in growth hormone deficiency: IV. Treatment with low doses of human growth hormone based on body weight. In order to define the minimum effective dose of human growth hormone (GH) in growth hormone deficient children, GH was administered to three groups of patients based on their body weight. Five children who received 0.01 International Unit (IU) GH/kg three times a week (tiw) failed to respond with a significant increase in their rate of growth. A dose of 0.03 IU GH/kg tiw increased the growth rate of 12 patients from 3.5 +/- 0.4 (SE) cm/year to 6.4 +/- 0.4 (SE) cm/year (P less than 0.001) during the first 12 months of therapy. Eight children (67%) larger than or equal to 6.0 cm/year. A similar increase growth rate from 3.6 +/- 0.4 (SE) cm/year to 7.3 +/- 0.4 (SE) cm/year (P less than 0.001) was observed over the first 12 months of therapy in 16 growth hormone deficient children who were given 0.06 IU GH/kg tiw. Thirteen children (81%) grew larger than or equal to 6.0 cm/year. During a second year of treatment, children receiving either 0.03 or 0.06 UI GH/kg tiw again showed a significant increase in their rate of growth. However, the response was significantly less than that observed during the first year of treatment. Comparison of these results with those available in the literature suggests that the most efficient, although not necessarily the optimal, initial dose of GH in children with growth hormone deficiency is 0.06 IU GH/kg administered three times a week."}
{"id": "PMID:188862", "title": "Observations concerning the binding of L-triiodothyronine in the human polymorphonuclear leukocyte.", "content": "To examine the subcellular locus of L-triiodothyronine (T3) binding in the human polymorphonuclear leukocyte, intact leukocytes (greater than 90% polymorphonuclear) were incubated with small tracer concentrations of [125I]T3 with or without an excess of non-radioactive T3. Measurement of the [125I]T3 content of several subcellular fractions revealed that the non-radioactive T3 had led to significant displacement of [125I]T3 from the nuclear fraction alone. After correction for degradation and non-specific binding of the added T3 in intact leukocytes from hypothyroid patients in which the endogenous T3 concentration would be minimal, the T3-nuclear binding interaction was found to have an equilibrium dissociation constant of 1.1 X 10(-10)M and a binding capacity of 4.3 fmol/1 X 10(7) cells. Pre-incubation of intact cells with non-radioactive T3 did not increase the subsequent specific binding of [125I]T3 by the nuclei isolated therefrom. The data indicate that: 1) the human polymorphonuclear leukocyte possesses saturable nuclear binding sites for T3, and 2) the sites appear to bind T3 without the intermediation of a cytosol receptor.", "contents": "Observations concerning the binding of L-triiodothyronine in the human polymorphonuclear leukocyte. To examine the subcellular locus of L-triiodothyronine (T3) binding in the human polymorphonuclear leukocyte, intact leukocytes (greater than 90% polymorphonuclear) were incubated with small tracer concentrations of [125I]T3 with or without an excess of non-radioactive T3. Measurement of the [125I]T3 content of several subcellular fractions revealed that the non-radioactive T3 had led to significant displacement of [125I]T3 from the nuclear fraction alone. After correction for degradation and non-specific binding of the added T3 in intact leukocytes from hypothyroid patients in which the endogenous T3 concentration would be minimal, the T3-nuclear binding interaction was found to have an equilibrium dissociation constant of 1.1 X 10(-10)M and a binding capacity of 4.3 fmol/1 X 10(7) cells. Pre-incubation of intact cells with non-radioactive T3 did not increase the subsequent specific binding of [125I]T3 by the nuclei isolated therefrom. The data indicate that: 1) the human polymorphonuclear leukocyte possesses saturable nuclear binding sites for T3, and 2) the sites appear to bind T3 without the intermediation of a cytosol receptor."}
{"id": "PMID:188863", "title": "Plaque assay of neonatal calf diarrhea virus and the neutralizing antibody in human sera.", "content": "Neonatal calf diarrhea virus (a bovine rotavirus) formed distinct plaques in monolayers of MA-104 cells, an established macacus rhesus monkey kidney cell line, when diethylaminoethyl dextran and trypsin were included in the overlay medium. By using this plaque assay method, titration of neutralizing antibody to neonatal calf diarrhea virus was made feasible. It was demonstrated that some human sera contained neutralizing antibody to this agent.", "contents": "Plaque assay of neonatal calf diarrhea virus and the neutralizing antibody in human sera. Neonatal calf diarrhea virus (a bovine rotavirus) formed distinct plaques in monolayers of MA-104 cells, an established macacus rhesus monkey kidney cell line, when diethylaminoethyl dextran and trypsin were included in the overlay medium. By using this plaque assay method, titration of neutralizing antibody to neonatal calf diarrhea virus was made feasible. It was demonstrated that some human sera contained neutralizing antibody to this agent."}
{"id": "PMID:188864", "title": "Antibodies to hepatitis A virus: patterns by two procedures.", "content": "Antibody to hepatitis A virus demonstrable by immune electron microscopy appeared early but remained at low levels for several weeks. Antibody detectable by immune adherence hemagglutination was delayed.", "contents": "Antibodies to hepatitis A virus: patterns by two procedures. Antibody to hepatitis A virus demonstrable by immune electron microscopy appeared early but remained at low levels for several weeks. Antibody detectable by immune adherence hemagglutination was delayed."}
{"id": "PMID:188865", "title": "Contained indirect viable-cell membrane immunofluorescence microassay for surface antigen analysis of cells infected with hazardous viruses.", "content": "A microtechnique for an indirect viable-cell membrane immunofluorescence titration assay was developed using Friend murine leukemia virus (F-MuLV)-producing cells and monospecific rabbit antisera to F-MuLV structural antigens. The assay was sensitive and displayed little variation within or between assays. Since moderate-risk tumor viruses, such as recently discovered primate oncornaviruses or feline leukemia virus (FeLV), may be hazardous to laboratory personnel, the assay was adapted for containment of cells infected with such viruses. Cells producing gibbon ape lymphoma virus or FeLV were grown in class III containment cabinets and transferred in sealed flasks to a class II laminar-flow cabinet, where the assay was performed. This micromethod not only conserved reagents but also minimized the numbers of moderate-risk tumor virus-infected cells handled at one time. Centrifugation was contained using custom-made devices shown to form a gas-tight seal over microtiter plates. Interspecies reactivity of monospecific rabbit antisera against F-MuLV structural antigen gp71, but not against p12, was demonstrated for surface antigens on FeLV-producing cells.", "contents": "Contained indirect viable-cell membrane immunofluorescence microassay for surface antigen analysis of cells infected with hazardous viruses. A microtechnique for an indirect viable-cell membrane immunofluorescence titration assay was developed using Friend murine leukemia virus (F-MuLV)-producing cells and monospecific rabbit antisera to F-MuLV structural antigens. The assay was sensitive and displayed little variation within or between assays. Since moderate-risk tumor viruses, such as recently discovered primate oncornaviruses or feline leukemia virus (FeLV), may be hazardous to laboratory personnel, the assay was adapted for containment of cells infected with such viruses. Cells producing gibbon ape lymphoma virus or FeLV were grown in class III containment cabinets and transferred in sealed flasks to a class II laminar-flow cabinet, where the assay was performed. This micromethod not only conserved reagents but also minimized the numbers of moderate-risk tumor virus-infected cells handled at one time. Centrifugation was contained using custom-made devices shown to form a gas-tight seal over microtiter plates. Interspecies reactivity of monospecific rabbit antisera against F-MuLV structural antigen gp71, but not against p12, was demonstrated for surface antigens on FeLV-producing cells."}
{"id": "PMID:188866", "title": "Collagenase and collagenase inhibitors in osteoarthritic and normal cartilage.", "content": "In advanced osteoarthritis, all of the cartilaginous components are lost from the joint surface. Although mechanisms exist for proteoglycan degradation, there is not known to be any system for removal of the collagen. This study suggests that the loss of the collagen components may be a function of articular cartilage collagenase. The enzyme in normal human cartilage is bound to an inhibitor and appears to be present in very small amounts. Attempts to demonstrate collagenase activity in ground human articular cartilage or in its lysosomal fraction were unsuccessful. 7-Day cartilage tissue cultures also failed to demonstrate the presence of the enzyme; but the same culture fluid, incubated with trypsin, showed significant degradation of collagen, suggesting that trypsin destroyed the inhibitor. 7-Day culture fluids were then chromatographed on a heparin-charged Sepharose 4B affinity column that had been activated with cyanogen bromide. This removed the inhibitor, and the chromatographed fluid from osteoarthritic cartilage released 42% of the incorporated counts of the collagen substrate, whereas normal cartilage released 10.1% and a trypsin control, 6.4%. Electrophoresis of the degradation products of the enzyme-collagen complex incubated at 37 degrees C revealed breakdown was complete to small dialyzable fragments, while at 25 degrees C larger fragments were split off.", "contents": "Collagenase and collagenase inhibitors in osteoarthritic and normal cartilage. In advanced osteoarthritis, all of the cartilaginous components are lost from the joint surface. Although mechanisms exist for proteoglycan degradation, there is not known to be any system for removal of the collagen. This study suggests that the loss of the collagen components may be a function of articular cartilage collagenase. The enzyme in normal human cartilage is bound to an inhibitor and appears to be present in very small amounts. Attempts to demonstrate collagenase activity in ground human articular cartilage or in its lysosomal fraction were unsuccessful. 7-Day cartilage tissue cultures also failed to demonstrate the presence of the enzyme; but the same culture fluid, incubated with trypsin, showed significant degradation of collagen, suggesting that trypsin destroyed the inhibitor. 7-Day culture fluids were then chromatographed on a heparin-charged Sepharose 4B affinity column that had been activated with cyanogen bromide. This removed the inhibitor, and the chromatographed fluid from osteoarthritic cartilage released 42% of the incorporated counts of the collagen substrate, whereas normal cartilage released 10.1% and a trypsin control, 6.4%. Electrophoresis of the degradation products of the enzyme-collagen complex incubated at 37 degrees C revealed breakdown was complete to small dialyzable fragments, while at 25 degrees C larger fragments were split off."}
{"id": "PMID:188867", "title": "Evidence that the superoxide-generating system of human leukocytes is associated with the cell surface.", "content": "Superoxide anion (O-2-) generation by human peripheral blood polymorphonuclear leukocytes is enhanced when these cells encounter appropriate soluble or particulate stimuli. O-2- generation requires intact, viable cells and proceeds independently of phagocytosis. To investigate the possibility that the O-2--generating system is associated with the outer surface of the polymorphonuclear leukocyte plasma membrane, we have examined the effects upon O-2- production of p-diazobenzenesulfonic acid, a reagent which can react predominantly with proteins of the external cell membrane. When normal human polymorphonuclear leukocytes were preincubated with cytochalasin B (to minimize endocytosis) and then exposed to the surface-active lectin, concanavalin A, the cells were stimulated to generate O-2- in a concentration- and time-dependent fashion and selectively to discharge the granule-associated enzyme, lysozyme, into the surrounding medium. These responses, as well as cellular binding of [H] concanavalin A, could be blocked by alpha-methyl-D-mannoside. Brief treatment (less than 5 min at 4 degrees C) of the cells with p-diazobenzenesulfonic acid (1.0-5.0 mM) significantly interfered with concanavalin A-mediated O-2- generation but had no influence upon lysozyme release or upon binding of [3H] concanavalin A. The diazonium salt did not alter cell viability or the specific activity of the cytoplasmic enzyme, lactate dehydrogenase (inhibitable under conditions which allowed entry of this reagent into the cytosol). p-Diazobenzenesulfonic acid, therefore, very likely exerted its effects at the cell surface of the intact polymorphonuclear leukocyte, selectively inhibiting O-2- production (either directly or indirectly) without influencing another response to lectin-cell contact: release of lysozyme. These results support the possibility that a polymorphonuclear leukocyte ectoenzyme is responsible for O-2- production.", "contents": "Evidence that the superoxide-generating system of human leukocytes is associated with the cell surface. Superoxide anion (O-2-) generation by human peripheral blood polymorphonuclear leukocytes is enhanced when these cells encounter appropriate soluble or particulate stimuli. O-2- generation requires intact, viable cells and proceeds independently of phagocytosis. To investigate the possibility that the O-2--generating system is associated with the outer surface of the polymorphonuclear leukocyte plasma membrane, we have examined the effects upon O-2- production of p-diazobenzenesulfonic acid, a reagent which can react predominantly with proteins of the external cell membrane. When normal human polymorphonuclear leukocytes were preincubated with cytochalasin B (to minimize endocytosis) and then exposed to the surface-active lectin, concanavalin A, the cells were stimulated to generate O-2- in a concentration- and time-dependent fashion and selectively to discharge the granule-associated enzyme, lysozyme, into the surrounding medium. These responses, as well as cellular binding of [H] concanavalin A, could be blocked by alpha-methyl-D-mannoside. Brief treatment (less than 5 min at 4 degrees C) of the cells with p-diazobenzenesulfonic acid (1.0-5.0 mM) significantly interfered with concanavalin A-mediated O-2- generation but had no influence upon lysozyme release or upon binding of [3H] concanavalin A. The diazonium salt did not alter cell viability or the specific activity of the cytoplasmic enzyme, lactate dehydrogenase (inhibitable under conditions which allowed entry of this reagent into the cytosol). p-Diazobenzenesulfonic acid, therefore, very likely exerted its effects at the cell surface of the intact polymorphonuclear leukocyte, selectively inhibiting O-2- production (either directly or indirectly) without influencing another response to lectin-cell contact: release of lysozyme. These results support the possibility that a polymorphonuclear leukocyte ectoenzyme is responsible for O-2- production."}
{"id": "PMID:188868", "title": "Oat-cell carcinoma of the oesophagus: a recently recognized entity.", "content": "A primary oat-cell carcinoma of the oesophagus is described with an adjacent squamous carcinoma, both parts having characteristic ultrastructure. The origin of this mixed tumour is discussed together with the literature on oesophageal carcinomas having an oat-cell pattern.", "contents": "Oat-cell carcinoma of the oesophagus: a recently recognized entity. A primary oat-cell carcinoma of the oesophagus is described with an adjacent squamous carcinoma, both parts having characteristic ultrastructure. The origin of this mixed tumour is discussed together with the literature on oesophageal carcinomas having an oat-cell pattern."}
{"id": "PMID:188869", "title": "Effect of storage on recovery of cytomegalovirus from necropsy tissue.", "content": "Cytomegalovirus (CMV) was isolated from lung tissue in 8 of 55 (14-6%) necropsies on patients who had received immunosuppressive therapy. Recovery of CMV was best (14 of 16 specimens, 87%) from fresh tissue that had been processed immediately. Storage of specimens at 4 degrees C before inoculation into cell cultures slightly reduced, to 58%, the recovery of CMV. However, conventional freezing of tissue to -- 20 degrees C for four to seven days significantly reduced the recovery of CMV, to 25% (p less than 0-001). In three of eight specimens from which virus was recovered, CMV inclusion bodies were found on tracheal smears. Sixty-five percent of the virus-negative group had measurable complement-fixing antibody in blood taken at necropsy, compared with 86% in the virus-positive group. However, there was no significant differences in antibody levels in the two groups. Our study indicates that specimens submitted for CMV isolation should be sent for virus isolation as rapidly as possible and should not be frozen. The level of antibody in a single serum taken in necropsy does not correlate well with morphological or cultural evidence of active infection.", "contents": "Effect of storage on recovery of cytomegalovirus from necropsy tissue. Cytomegalovirus (CMV) was isolated from lung tissue in 8 of 55 (14-6%) necropsies on patients who had received immunosuppressive therapy. Recovery of CMV was best (14 of 16 specimens, 87%) from fresh tissue that had been processed immediately. Storage of specimens at 4 degrees C before inoculation into cell cultures slightly reduced, to 58%, the recovery of CMV. However, conventional freezing of tissue to -- 20 degrees C for four to seven days significantly reduced the recovery of CMV, to 25% (p less than 0-001). In three of eight specimens from which virus was recovered, CMV inclusion bodies were found on tracheal smears. Sixty-five percent of the virus-negative group had measurable complement-fixing antibody in blood taken at necropsy, compared with 86% in the virus-positive group. However, there was no significant differences in antibody levels in the two groups. Our study indicates that specimens submitted for CMV isolation should be sent for virus isolation as rapidly as possible and should not be frozen. The level of antibody in a single serum taken in necropsy does not correlate well with morphological or cultural evidence of active infection."}
{"id": "PMID:188870", "title": "Tropical myositis: ultrastructural studies.", "content": "Specimens of muscle were obtained from non-suppurating lesions of nine patients with tropical myositis. When examined in an electron microscope, these revealed patchy myocytolysis with loss of band structure. Perimysial cells were also degenerate. Sections from two out of nine patients revealed intracellular vesicles, about 80 nm in diameter, some of which contained 10 nm granules. These vesicles were seen budding from cell membranes and resembled virus particles. The focal necrosis with which they are associated and their absence from control sections support the concept that they are related to the disease process.", "contents": "Tropical myositis: ultrastructural studies. Specimens of muscle were obtained from non-suppurating lesions of nine patients with tropical myositis. When examined in an electron microscope, these revealed patchy myocytolysis with loss of band structure. Perimysial cells were also degenerate. Sections from two out of nine patients revealed intracellular vesicles, about 80 nm in diameter, some of which contained 10 nm granules. These vesicles were seen budding from cell membranes and resembled virus particles. The focal necrosis with which they are associated and their absence from control sections support the concept that they are related to the disease process."}
{"id": "PMID:188871", "title": "Cerebrospinal fluid immunoglobulin quotients, kappa/lambda ratios, and viral antibody titres in neurological disease.", "content": "A description has been given of cerebrospinal fluid (CSF) immunoglobulins in 355 patients with demyelinating, infectious, neuropathic, and other neurological disorders. An increase in the CSF IgG/albumin quotient was observed in 19/36 (53%) cases of definite multiple sclerosis (MS), in 13/47 (28%) cases of probable or possible MS, in 6/9 (67%) cases of proven herpes simplex viral encephalitis (HSVE), in 3/4 (75%) cases of neurosyphilis, in 1/1 case of subacute sclerosing panencephalitis (SSPE), in 2/9 )22%) cases of other central nervous system infections, and in 2/12 (17%) cases of polyneuritis when compared with a group of 236 patients having other neurological disorders. In constrast, a relative increase in the CSF IgA of IgM was seen only in some of the patients with central nervous system infections. It was also found that the quotient CSF/serum IgG, expressed as a percentage of the CSF/serum albumin, was better in distinguishing patients with definite or suspected MS from those with other neurological disorders than the quotients IgG/albumin or IgG/total protein. The CSF K/lambda ratio and the CSF and serum complement-fixing antibody titre to measles and herpes simplex virus were measured in many of the patients. In general, abnormalities of these measurements were associated with raised IgG/albumin quotients. However, in eight patients with definite or suspected MS, a normal IgG/albumin quotient was found with abnormal CSF K/lambda ratios (6 cases) or abnormal CSF titres of measles antibody (7 cases). In addition, two patients, with HSVE had normal IgG/albumin ratios but detectable herpes antibody in the CSF. These findings suggest that the measurement of the relative concentration of CSF immunoglobulin in combination with the K/lambda ratio and antibody titre to various viruses may supplement each other in the endeavour to detect central nervous system immunglobulin sysnthesis in neurological diseases.", "contents": "Cerebrospinal fluid immunoglobulin quotients, kappa/lambda ratios, and viral antibody titres in neurological disease. A description has been given of cerebrospinal fluid (CSF) immunoglobulins in 355 patients with demyelinating, infectious, neuropathic, and other neurological disorders. An increase in the CSF IgG/albumin quotient was observed in 19/36 (53%) cases of definite multiple sclerosis (MS), in 13/47 (28%) cases of probable or possible MS, in 6/9 (67%) cases of proven herpes simplex viral encephalitis (HSVE), in 3/4 (75%) cases of neurosyphilis, in 1/1 case of subacute sclerosing panencephalitis (SSPE), in 2/9 )22%) cases of other central nervous system infections, and in 2/12 (17%) cases of polyneuritis when compared with a group of 236 patients having other neurological disorders. In constrast, a relative increase in the CSF IgA of IgM was seen only in some of the patients with central nervous system infections. It was also found that the quotient CSF/serum IgG, expressed as a percentage of the CSF/serum albumin, was better in distinguishing patients with definite or suspected MS from those with other neurological disorders than the quotients IgG/albumin or IgG/total protein. The CSF K/lambda ratio and the CSF and serum complement-fixing antibody titre to measles and herpes simplex virus were measured in many of the patients. In general, abnormalities of these measurements were associated with raised IgG/albumin quotients. However, in eight patients with definite or suspected MS, a normal IgG/albumin quotient was found with abnormal CSF K/lambda ratios (6 cases) or abnormal CSF titres of measles antibody (7 cases). In addition, two patients, with HSVE had normal IgG/albumin ratios but detectable herpes antibody in the CSF. These findings suggest that the measurement of the relative concentration of CSF immunoglobulin in combination with the K/lambda ratio and antibody titre to various viruses may supplement each other in the endeavour to detect central nervous system immunglobulin sysnthesis in neurological diseases."}
{"id": "PMID:188873", "title": "Lack of bronchial beta adrenoceptor resistance in asthmatics during long-term treatment with terbutaline.", "content": "The increasing mortality in acute asthma noted during the sixties has been ascribed to resistance of the beta 2 receptors of the bronchi due to treatment with beta-stimulating drugs. This study questions that theory. Eight patients with reversible airways obstruction were studied. Treatment with oral terbutaline 5 mg 3 times a day was given for 1 yr. Thereafter, terbutaline as metered aerosol was added in the dose of 2 puffs (0.5 mg) 4 times a day for 4 days and 6 puffs (1.5 mg) 4 times a day for further 4 days. The responsiveness of the receptors of bronchi, heart, skeletal muscles, and peripheral vessels was tested before and after 1, 2, 3, 6, 9, and 12 mo of treatment with oral terbutaline and after the two 4-day periods with inhaled terbutaline. The receptors were tested by infusion of increasing doses of isoprenaline, so that dose-response curves for isoprenaline were recorded. No signs of resistance of the beta 2 receptors of the bronchi developed during the terbutaline treatment period. Thus no even spray in moderate overdose caused resistance. Within 1 mo of treatment with oral terbutaline, resistance developed to the tremorogenic effect of terbutaline. Six of the 8 patients showed no signs of development of resistance to the chronotropic effect of isoprenaline. No signs were found of resistance of the beta 2 receptors of peripheral blood vessels.", "contents": "Lack of bronchial beta adrenoceptor resistance in asthmatics during long-term treatment with terbutaline. The increasing mortality in acute asthma noted during the sixties has been ascribed to resistance of the beta 2 receptors of the bronchi due to treatment with beta-stimulating drugs. This study questions that theory. Eight patients with reversible airways obstruction were studied. Treatment with oral terbutaline 5 mg 3 times a day was given for 1 yr. Thereafter, terbutaline as metered aerosol was added in the dose of 2 puffs (0.5 mg) 4 times a day for 4 days and 6 puffs (1.5 mg) 4 times a day for further 4 days. The responsiveness of the receptors of bronchi, heart, skeletal muscles, and peripheral vessels was tested before and after 1, 2, 3, 6, 9, and 12 mo of treatment with oral terbutaline and after the two 4-day periods with inhaled terbutaline. The receptors were tested by infusion of increasing doses of isoprenaline, so that dose-response curves for isoprenaline were recorded. No signs of resistance of the beta 2 receptors of the bronchi developed during the terbutaline treatment period. Thus no even spray in moderate overdose caused resistance. Within 1 mo of treatment with oral terbutaline, resistance developed to the tremorogenic effect of terbutaline. Six of the 8 patients showed no signs of development of resistance to the chronotropic effect of isoprenaline. No signs were found of resistance of the beta 2 receptors of peripheral blood vessels."}
{"id": "PMID:188945", "title": "Reliability of the serological method of examination as a basis for diagnosis of associated respiratory virus infections.", "content": "The reliability of the results of serological examination in diagnostics of associated infections was studied on a model of artificially provoked vaccinal infections in humans and in laboratory animals. The effect of administered monopreparations on changes in the level of both homologous and heterologous antibodies was tested. The character of immunological changes following simultaneous administration of two or more respiratory viruses was analysed and the effect of these viruses in diseases of divers etiology was studied. According to the results of experiments on laboratory animals, repeated administration of any of the earlier used respiratory viruses stimulated the accumulation of only homologous antibodies while heterologous antibodies did not increase at all.", "contents": "Reliability of the serological method of examination as a basis for diagnosis of associated respiratory virus infections. The reliability of the results of serological examination in diagnostics of associated infections was studied on a model of artificially provoked vaccinal infections in humans and in laboratory animals. The effect of administered monopreparations on changes in the level of both homologous and heterologous antibodies was tested. The character of immunological changes following simultaneous administration of two or more respiratory viruses was analysed and the effect of these viruses in diseases of divers etiology was studied. According to the results of experiments on laboratory animals, repeated administration of any of the earlier used respiratory viruses stimulated the accumulation of only homologous antibodies while heterologous antibodies did not increase at all."}
{"id": "PMID:188946", "title": "[Stich-plaque test--an economic method for quantitative determination of viruses].", "content": "An economic method for quantitative assay of viruses is presented. In this \"canule stick-plaque test\" (German abbreviation SPT) samples of viruses, geometrically diluted and taken up by a canule, are inoculated by sticking into monolayer cell cultures overlayed with agar medium. A plaquelike CPE detectable by neutral red staining develops in the area of the inoculation. The frequency of this CPE formation depends on the concentration of viruses in the inoculated dilution. This dose-response allows calculation of the ID 50. In this way it is possible to carry out titration involving 6 dilutions and 10 inoculations per dilution using 3 common Petri dishes (6 cm in diameter), only. The sensitivity , accuracy, and reproductibility of this method are described and discussed.", "contents": "[Stich-plaque test--an economic method for quantitative determination of viruses]. An economic method for quantitative assay of viruses is presented. In this \"canule stick-plaque test\" (German abbreviation SPT) samples of viruses, geometrically diluted and taken up by a canule, are inoculated by sticking into monolayer cell cultures overlayed with agar medium. A plaquelike CPE detectable by neutral red staining develops in the area of the inoculation. The frequency of this CPE formation depends on the concentration of viruses in the inoculated dilution. This dose-response allows calculation of the ID 50. In this way it is possible to carry out titration involving 6 dilutions and 10 inoculations per dilution using 3 common Petri dishes (6 cm in diameter), only. The sensitivity , accuracy, and reproductibility of this method are described and discussed."}
{"id": "PMID:188948", "title": "The use of early embryo aggregation derived mouse chimaeras. II. The study of disease processes.", "content": "Early embryo aggregation derived mouse chimeras have proven an extremely valuable tool to study development of disease processes. In this respect chimaeras prove a unique opportunity to study the interaction between cells genetically pre-destined to become diseased and a normal cell population within the same animal. In this situation chimaeras can be studied in view of possible 'correction' of the disease by the provision of a population of normal host cells and/or their products. Various host deficiency states including classic immune deficiency, potentially 'deficient' anemias and tumours have been studied--the subject of the review here.", "contents": "The use of early embryo aggregation derived mouse chimaeras. II. The study of disease processes. Early embryo aggregation derived mouse chimeras have proven an extremely valuable tool to study development of disease processes. In this respect chimaeras prove a unique opportunity to study the interaction between cells genetically pre-destined to become diseased and a normal cell population within the same animal. In this situation chimaeras can be studied in view of possible 'correction' of the disease by the provision of a population of normal host cells and/or their products. Various host deficiency states including classic immune deficiency, potentially 'deficient' anemias and tumours have been studied--the subject of the review here."}
{"id": "PMID:188949", "title": "A unique cytoplasmic structure in papular histiocytoma.", "content": "Intracytoplasmic granules with a unique and highly complex ultrastructure, have been observed within the cellular infiltrate of the lesions of two patients with papular histiocytosis. Examination of serial sections has enabled construction of a three-dimensional model of these granules, which appear to be composed of an elaborate arrangement of membranes and vesicles. Two hypotheses (endocytosis and exocytosis) are proposed for the mode of formation of these unique cytoplasmic structures.", "contents": "A unique cytoplasmic structure in papular histiocytoma. Intracytoplasmic granules with a unique and highly complex ultrastructure, have been observed within the cellular infiltrate of the lesions of two patients with papular histiocytosis. Examination of serial sections has enabled construction of a three-dimensional model of these granules, which appear to be composed of an elaborate arrangement of membranes and vesicles. Two hypotheses (endocytosis and exocytosis) are proposed for the mode of formation of these unique cytoplasmic structures."}
{"id": "PMID:188950", "title": "Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Basic study and laboratory standardization.", "content": "The present four-center collaborative study was undertaken in an attempt to define the best vaccine and/or vaccination procedure for use in areas of the world that are free of smallpox. The study was designed to compare the effect of different vaccinial strains, viral concentrations, and routes of administration on the morbidity and antibody response associated with primary vaccination and standard challenge revaccination. Primary vaccinations were performed on 1,585 children; 49.6% of the children were vaccinated by the percutaneous route, and 50.4% received vaccine subcutaneously. The overall age and sex distributions of percutaneous and subcutaneous vaccinees were comparable, but there were marked differences in participants among the four study centers. Vaccines in Kentucky had a greater mean age; the greatest number of Negroid children were enrolled in St. Louis, and more of them were vaccinated by the subcutaneous route; and the dropout rate was much greater in San Diego and Colorado. An analysis of comparative interlaboratory serologic procedures with the use of 20 coded duplicate samples of serum revealed good agreement in the hemagglutination-inhibition test; results of neutralization tests had greater variability of mean titers. On duplicate samples of serum from study participants there was generally good correlation between each of the four study centers and the Center for Disease Control's reference laboratory in titers of hemagglutination-inhibiting antibody. In contrast, 38% of the neutralization titers determined at the four study centers were greater than or equal to 0.67 log10 higher than the respective titers noted at the Center for Disease Control.", "contents": "Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Basic study and laboratory standardization. The present four-center collaborative study was undertaken in an attempt to define the best vaccine and/or vaccination procedure for use in areas of the world that are free of smallpox. The study was designed to compare the effect of different vaccinial strains, viral concentrations, and routes of administration on the morbidity and antibody response associated with primary vaccination and standard challenge revaccination. Primary vaccinations were performed on 1,585 children; 49.6% of the children were vaccinated by the percutaneous route, and 50.4% received vaccine subcutaneously. The overall age and sex distributions of percutaneous and subcutaneous vaccinees were comparable, but there were marked differences in participants among the four study centers. Vaccines in Kentucky had a greater mean age; the greatest number of Negroid children were enrolled in St. Louis, and more of them were vaccinated by the subcutaneous route; and the dropout rate was much greater in San Diego and Colorado. An analysis of comparative interlaboratory serologic procedures with the use of 20 coded duplicate samples of serum revealed good agreement in the hemagglutination-inhibition test; results of neutralization tests had greater variability of mean titers. On duplicate samples of serum from study participants there was generally good correlation between each of the four study centers and the Center for Disease Control's reference laboratory in titers of hemagglutination-inhibiting antibody. In contrast, 38% of the neutralization titers determined at the four study centers were greater than or equal to 0.67 log10 higher than the respective titers noted at the Center for Disease Control."}
{"id": "PMID:188951", "title": "Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Primary percutaneous vaccination.", "content": "In an investigation of the antigenicity and reactogenicity of four smallpox vaccines, 786 children received primary percutaneous vaccination with vaccine in one of three concentrations, 10(6), 10(7), or10(8) pock-forming units/ml. Dose-response curves indicated that the three licensed vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membrane, and the Lister vaccine) had similar potencies, but the CV-1 strain was about 10-fold less infectious. CV-1 also produced smaller skin lesions than the other three vaccines, and the incidence of fever in CV-1 vaccines who developed either \"major reactions\" or serum antibody was not significantly different from that in children in all vaccine groups with no evidence of \"take.\" Hemmagglutination-inhibiting antibody was consistently seen in individuals who received potent New York City and Lister vaccines, and neutralizing antibody was induced in 82%-85% of children in this group who had some evidence of take (production of hemagglutination-inhibiting antibody or or major reaction). Only 30% of CV-1 vaccines with takes produced neutralizing antibody. Minor complications occurred in all groups, but most often in children who received the New York City strains.\"", "contents": "Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Primary percutaneous vaccination. In an investigation of the antigenicity and reactogenicity of four smallpox vaccines, 786 children received primary percutaneous vaccination with vaccine in one of three concentrations, 10(6), 10(7), or10(8) pock-forming units/ml. Dose-response curves indicated that the three licensed vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membrane, and the Lister vaccine) had similar potencies, but the CV-1 strain was about 10-fold less infectious. CV-1 also produced smaller skin lesions than the other three vaccines, and the incidence of fever in CV-1 vaccines who developed either \"major reactions\" or serum antibody was not significantly different from that in children in all vaccine groups with no evidence of \"take.\" Hemmagglutination-inhibiting antibody was consistently seen in individuals who received potent New York City and Lister vaccines, and neutralizing antibody was induced in 82%-85% of children in this group who had some evidence of take (production of hemagglutination-inhibiting antibody or or major reaction). Only 30% of CV-1 vaccines with takes produced neutralizing antibody. Minor complications occurred in all groups, but most often in children who received the New York City strains.\""}
{"id": "PMID:188952", "title": "Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary percutaneous vaccination.", "content": "A standard challenge with percutaneous smallpox vaccine was administered to 629 children six to 12 months after percutaneous primary inoculation with one of four vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membranes, the Lister vaccine, or the CV-1 strain). Of those who had had major reactions on primary vaccination, 8%-21% responded to revasccination with a typical primary-type skin response. In contrast, such a primary-type response occurred in 50% of those who on primary vaccination had developed serum antibody in the absence of major reactions and in 83% of those who had had no serologic or clinical evidence of primary \"take.\" Skin lesions on revaccination tended to be largest in thosewhose primary vaccination was with CV-1, although fever and minor complications were not more frequent. Moreover, even in children who had received CV-1 vaccine, skin responses to challenge vaccine were clearly attenuated when compared with responses of children who had not had takes on primary vaccination. Sizes of lesions and acceleration of skin erytherma after challenge were related in most children to titers of both hemagglutination-inhibiting and neutralizing antibody at the time of revaccination. One month after revaccination, neutralizing antibody was present in 93%-96% of those with takes onprimary vaccination with New York City or Lister vaccines, but only 75% of CV-1 vaccines.", "contents": "Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary percutaneous vaccination. A standard challenge with percutaneous smallpox vaccine was administered to 629 children six to 12 months after percutaneous primary inoculation with one of four vaccines (New York City Board of Health strains grown in calf lymph or chorioallantoic membranes, the Lister vaccine, or the CV-1 strain). Of those who had had major reactions on primary vaccination, 8%-21% responded to revasccination with a typical primary-type skin response. In contrast, such a primary-type response occurred in 50% of those who on primary vaccination had developed serum antibody in the absence of major reactions and in 83% of those who had had no serologic or clinical evidence of primary \"take.\" Skin lesions on revaccination tended to be largest in thosewhose primary vaccination was with CV-1, although fever and minor complications were not more frequent. Moreover, even in children who had received CV-1 vaccine, skin responses to challenge vaccine were clearly attenuated when compared with responses of children who had not had takes on primary vaccination. Sizes of lesions and acceleration of skin erytherma after challenge were related in most children to titers of both hemagglutination-inhibiting and neutralizing antibody at the time of revaccination. One month after revaccination, neutralizing antibody was present in 93%-96% of those with takes onprimary vaccination with New York City or Lister vaccines, but only 75% of CV-1 vaccines."}
{"id": "PMID:188953", "title": "Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary subcutaneous vaccination.", "content": "Six months after subcutaneous vaccination with one of four smallpox vaccines, 655 children were challenged with a standard percutaneous smallpox vaccine. Response to reimmunization was characterized by a significant acceleration and diminution of skin response, but not to the degree seen in an equivalent group who had received their primary immunization percutaneously. Fever after revaccination was absent if there had been a \"take\" with primary subcutaneous vaccination. The overall incidence of minor vaccine-related complications with revaccination was 2-1/2%. The neutralizing antibody response to revaccination was markedly reduced, as compared to that of children who received either one or two successful percutaneous vaccinations. Subcutaneous vaccination followed by percutaneous vaccination is not recommended as a schedule for smallpox immunization, because complications are not avoided, and the incidence and mean titer of resultant neutralizing antibody are low.", "contents": "Clinical and serologic study of four smallpox vaccines comparing variations of dose and route of administration. Standard percutaneous revaccination of children who receive primary subcutaneous vaccination. Six months after subcutaneous vaccination with one of four smallpox vaccines, 655 children were challenged with a standard percutaneous smallpox vaccine. Response to reimmunization was characterized by a significant acceleration and diminution of skin response, but not to the degree seen in an equivalent group who had received their primary immunization percutaneously. Fever after revaccination was absent if there had been a \"take\" with primary subcutaneous vaccination. The overall incidence of minor vaccine-related complications with revaccination was 2-1/2%. The neutralizing antibody response to revaccination was markedly reduced, as compared to that of children who received either one or two successful percutaneous vaccinations. Subcutaneous vaccination followed by percutaneous vaccination is not recommended as a schedule for smallpox immunization, because complications are not avoided, and the incidence and mean titer of resultant neutralizing antibody are low."}
{"id": "PMID:188954", "title": "Correlation of herpes simplex virus types 1 and 2 with clinical features of infection.", "content": "Strains (338) of herpes simplex virus (HSV) were isolated in Stockholm during 1965-1974. By immunoelectroosmophoresis it was possible to identify all strains as either HSV type 1 (HSV-1) or 2 (HSV-2). No strains of intermediate antigenic type or with untypable characteristics were found. The antigenic type of HSV was correlated with body site and clinical features of infection. A case of severe, recurrent, abdominal pain in association with HSV-2 infection is described. In one patient with acute aseptic meningitis, both coxsackievirus A9 and HSV-2 were isolated from the same specimen of cerebrospinal fluid. Serology suggested a primary infection with coxsackievirus A9 and a recurrent HSV-2 infection. HSV-1 was isolated from specimens of cerebrospinal fluid. Serology suggested a primary infection with coxsackievirus A9 and a recurrent HSV-2 infection. HSV-1 was isolated from specimens of cerebrospinal fluid from two of four adults with HSV encephalitis.", "contents": "Correlation of herpes simplex virus types 1 and 2 with clinical features of infection. Strains (338) of herpes simplex virus (HSV) were isolated in Stockholm during 1965-1974. By immunoelectroosmophoresis it was possible to identify all strains as either HSV type 1 (HSV-1) or 2 (HSV-2). No strains of intermediate antigenic type or with untypable characteristics were found. The antigenic type of HSV was correlated with body site and clinical features of infection. A case of severe, recurrent, abdominal pain in association with HSV-2 infection is described. In one patient with acute aseptic meningitis, both coxsackievirus A9 and HSV-2 were isolated from the same specimen of cerebrospinal fluid. Serology suggested a primary infection with coxsackievirus A9 and a recurrent HSV-2 infection. HSV-1 was isolated from specimens of cerebrospinal fluid. Serology suggested a primary infection with coxsackievirus A9 and a recurrent HSV-2 infection. HSV-1 was isolated from specimens of cerebrospinal fluid from two of four adults with HSV encephalitis."}
{"id": "PMID:188956", "title": "Abnormalities of cholesterol-phospholipid composition in platelets and low-density lipoproteins of human hyperbetalipoproteinemia.", "content": "Platelets from most patients with type IIa hyperlipoproteinemia (IIa) aggregate in the presence of lower concentrations of epinephrine and adenosine diphosphate (ADP) than are necessary to aggregate normal platelets. We have observed a comparable functional alteration in human platelets made cholesterol-rich in vitro by incubation in a milieu artificially rich in free cholesterol relative to phospholipid. We therefore examined platelet aggregation and lipid composition of platelets and of plasma low-density lipoprotein (LDL) in 19 individuals with IIa (including three homozygotes), seven normolipidemic individuals with symptomatic, angiographically-documented coronary atherosclerosis (atherosclerosis group), and 23 asymptomatic, normolipidemic subjects (control group). More than 99 percent of platelet cholesterol was unesterified. There was a 7 percent increase in the cholesterol content of whole platelets per mole of platelet phospholipid (C/PL) in IIa as compared to normal controls. This resulted from a 22 percent increase in the C/PL of IIa platelet membranes with no change in the C/PL of the soluble or granule fraction. The C/PL of IIa platelets was 6 percent greater than that of platelets from patients with atherosclerosis. As compared to those of normal controls, IIa platelets aggregated in response to a ninefold lower concentration of epinephrine (p less than 0.001) and a twofold lower concentration of ADP (p less than 0.02). The response of atherosclerosis platelets to these agents was comparable to that of controls. In all groups, there was a negative correlation between the log concentration of epinephrine required to produce complete platelet aggregation and the platelet C/PL (r = -0.06; p less than 0.002). The composition of LDL isolated from the plasma of patients with IIa was characterized by a 39 percent increase in the amount of free cholesterol relative to protein and a 35 percent increase in C/PL, as compared with control LDL. These values were increased 23 and 19 percent, respecitvely, when IIa was compared with the atherosclerosis group. In all groups the C/PL of LDL correlated well with the C/PL of platelets (r = =0.61; p less than 0.001). However, a simple cause-and-effect relationship did not appear to exist since (1) erythrocyte membrane C/PL was not affected and (2) normal platelets or erythrocytes underwent no change in C/PL during 18 hours' incubation in IIa plasma. These studies demonstrate that LDL and platelets in IIa contain an increased amount of free cholesterol relative to its principal solubilizer, phospholipid. In platelets this correlates with an increased sensitivity to aggregating agents. Moreover, the similarity between the functional abnormality in IIa platelets and that previously observed in normal platelets made cholesterol-rich in vitro suggests that the lipid composition of platelet membranes may have a direct effect on the function of platelets in man.", "contents": "Abnormalities of cholesterol-phospholipid composition in platelets and low-density lipoproteins of human hyperbetalipoproteinemia. Platelets from most patients with type IIa hyperlipoproteinemia (IIa) aggregate in the presence of lower concentrations of epinephrine and adenosine diphosphate (ADP) than are necessary to aggregate normal platelets. We have observed a comparable functional alteration in human platelets made cholesterol-rich in vitro by incubation in a milieu artificially rich in free cholesterol relative to phospholipid. We therefore examined platelet aggregation and lipid composition of platelets and of plasma low-density lipoprotein (LDL) in 19 individuals with IIa (including three homozygotes), seven normolipidemic individuals with symptomatic, angiographically-documented coronary atherosclerosis (atherosclerosis group), and 23 asymptomatic, normolipidemic subjects (control group). More than 99 percent of platelet cholesterol was unesterified. There was a 7 percent increase in the cholesterol content of whole platelets per mole of platelet phospholipid (C/PL) in IIa as compared to normal controls. This resulted from a 22 percent increase in the C/PL of IIa platelet membranes with no change in the C/PL of the soluble or granule fraction. The C/PL of IIa platelets was 6 percent greater than that of platelets from patients with atherosclerosis. As compared to those of normal controls, IIa platelets aggregated in response to a ninefold lower concentration of epinephrine (p less than 0.001) and a twofold lower concentration of ADP (p less than 0.02). The response of atherosclerosis platelets to these agents was comparable to that of controls. In all groups, there was a negative correlation between the log concentration of epinephrine required to produce complete platelet aggregation and the platelet C/PL (r = -0.06; p less than 0.002). The composition of LDL isolated from the plasma of patients with IIa was characterized by a 39 percent increase in the amount of free cholesterol relative to protein and a 35 percent increase in C/PL, as compared with control LDL. These values were increased 23 and 19 percent, respecitvely, when IIa was compared with the atherosclerosis group. In all groups the C/PL of LDL correlated well with the C/PL of platelets (r = =0.61; p less than 0.001). However, a simple cause-and-effect relationship did not appear to exist since (1) erythrocyte membrane C/PL was not affected and (2) normal platelets or erythrocytes underwent no change in C/PL during 18 hours' incubation in IIa plasma. These studies demonstrate that LDL and platelets in IIa contain an increased amount of free cholesterol relative to its principal solubilizer, phospholipid. In platelets this correlates with an increased sensitivity to aggregating agents. Moreover, the similarity between the functional abnormality in IIa platelets and that previously observed in normal platelets made cholesterol-rich in vitro suggests that the lipid composition of platelet membranes may have a direct effect on the function of platelets in man."}
{"id": "PMID:188957", "title": "Heterotopic cervical salivary glands.", "content": "A four-year-old girl presented with bilaterally symmetrical cutaneous orifices situated at the junction of the middle and lower thirds of the sterno-cleido-mastoid muscle. The preoperative diagnosis was lateral cervical, or branchial, sinuses. At operation the sinus tracts were found to extend only 2 cm. deep to the skin surface, and histological examination revealed mixed salivary glands. The literature is reviewed and the differential diagnosis of sinus orifices in the lower, anterior part of the neck is discussed.", "contents": "Heterotopic cervical salivary glands. A four-year-old girl presented with bilaterally symmetrical cutaneous orifices situated at the junction of the middle and lower thirds of the sterno-cleido-mastoid muscle. The preoperative diagnosis was lateral cervical, or branchial, sinuses. At operation the sinus tracts were found to extend only 2 cm. deep to the skin surface, and histological examination revealed mixed salivary glands. The literature is reviewed and the differential diagnosis of sinus orifices in the lower, anterior part of the neck is discussed."}
{"id": "PMID:188959", "title": "Enzymic synthesis of ether types of choline and ethanolamine phosphoglycerides by microsomal fractions from rat brain and liver.", "content": "The formation of product by ethanolamine phosphotransferases (EC 2.7.8.1) and cholinephosphotransferases (EC 2.7.8.2) in microsomal fractions from brains and livers of mature rats is increased several fold by 1,2-diacyl-sn-glycerols. With the addition of 1-alkyl-2-acyl-sn-glycerols, we have found an 11-fold increase with brain microsomes and a 20-fold increase with lvier microsomes in the synthesis of choline ether lipids (1-alkyl-2-acyl- and 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphorylcholines). For the synthesis of ethanolamine ether lipids (1-alkyl-2-acyl and 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphorylethanolamines), the stimulation of alkylacylglycerols was 7-fold for brain microsomes and 18-fold for liver microsomes. The alkylacyl glycerols (8 mM) also inhibited the synthesis of diacyl phosphoglycerides by 44 to 65%, indicating that the same ethanolaminephosphotransferases and cholinephosphotransferases are utilized for the synthesis of alkylacyl phosphoglycerides and diacyl phosphoglycerides. A desaturation of the alkyl groups may take place in the same reaction mixture. The rate of incorporation of phosphorylcholine into alkenylacyl glycerophosphorylcholines (choline plasmalogens) with alkylacylglycerols, cytidine diphosphate choline, and liver microsomes was 15 nmoles per mg protein per hour. The in vitro synthesis of choline plasmalogens with alkylacylglycerols had not been observed previously. The corresponding rate of incorporation of phosphorylethanolamine into ethanolamine plasmalogens was 10 nmoles per mg protein per hour, a value greater than any of the previously reported values for ethanolamine plasmalogen formation from alkylacyl glycerophosphorylethanolamines.", "contents": "Enzymic synthesis of ether types of choline and ethanolamine phosphoglycerides by microsomal fractions from rat brain and liver. The formation of product by ethanolamine phosphotransferases (EC 2.7.8.1) and cholinephosphotransferases (EC 2.7.8.2) in microsomal fractions from brains and livers of mature rats is increased several fold by 1,2-diacyl-sn-glycerols. With the addition of 1-alkyl-2-acyl-sn-glycerols, we have found an 11-fold increase with brain microsomes and a 20-fold increase with lvier microsomes in the synthesis of choline ether lipids (1-alkyl-2-acyl- and 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphorylcholines). For the synthesis of ethanolamine ether lipids (1-alkyl-2-acyl and 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphorylethanolamines), the stimulation of alkylacylglycerols was 7-fold for brain microsomes and 18-fold for liver microsomes. The alkylacyl glycerols (8 mM) also inhibited the synthesis of diacyl phosphoglycerides by 44 to 65%, indicating that the same ethanolaminephosphotransferases and cholinephosphotransferases are utilized for the synthesis of alkylacyl phosphoglycerides and diacyl phosphoglycerides. A desaturation of the alkyl groups may take place in the same reaction mixture. The rate of incorporation of phosphorylcholine into alkenylacyl glycerophosphorylcholines (choline plasmalogens) with alkylacylglycerols, cytidine diphosphate choline, and liver microsomes was 15 nmoles per mg protein per hour. The in vitro synthesis of choline plasmalogens with alkylacylglycerols had not been observed previously. The corresponding rate of incorporation of phosphorylethanolamine into ethanolamine plasmalogens was 10 nmoles per mg protein per hour, a value greater than any of the previously reported values for ethanolamine plasmalogen formation from alkylacyl glycerophosphorylethanolamines."}
{"id": "PMID:188960", "title": "Analysis of rat serum apolipoproteins by isoelectric focusing. I. Studies on the middle molecular weight subunits.", "content": "Analytical isoelectric focusing (IEF) has been applied to the study of the apolipoprotein components of rat serum high density and very low density lipoproteins. The apolipoproteins were separated on 7.5% polyacrylamide gels containing 6.8% urea, with a pH gradient of 4-6. The middle molecular weight range apolipoproteins were identified on IEF gels by the use of apolipoproteins purified by electrophoresis on gels containing sodium dodecyl sulfate (SDS). The A-1 protein focused as 4 to 5 bands from pH 5.46 to 5.82; the A-IV protein and the arginine-rich protein each focused as 4 to 6 bands from pH 5.31 to 5.46. The low molecular weight proteins focused from pH. 4.43 to 4.83 and are the subject of a separate communication. Comparisons of the IEF method with SDS gel electrophoresis, polyacrylamide gel electrophoresis in urea, and Sephadex chromatography are also reported. Additional studies were also carried out that tend to rule out carbamylation or incomplete unfolding of the proteins in the presence of urea as the causes of the observed heterogeneity.", "contents": "Analysis of rat serum apolipoproteins by isoelectric focusing. I. Studies on the middle molecular weight subunits. Analytical isoelectric focusing (IEF) has been applied to the study of the apolipoprotein components of rat serum high density and very low density lipoproteins. The apolipoproteins were separated on 7.5% polyacrylamide gels containing 6.8% urea, with a pH gradient of 4-6. The middle molecular weight range apolipoproteins were identified on IEF gels by the use of apolipoproteins purified by electrophoresis on gels containing sodium dodecyl sulfate (SDS). The A-1 protein focused as 4 to 5 bands from pH 5.46 to 5.82; the A-IV protein and the arginine-rich protein each focused as 4 to 6 bands from pH 5.31 to 5.46. The low molecular weight proteins focused from pH. 4.43 to 4.83 and are the subject of a separate communication. Comparisons of the IEF method with SDS gel electrophoresis, polyacrylamide gel electrophoresis in urea, and Sephadex chromatography are also reported. Additional studies were also carried out that tend to rule out carbamylation or incomplete unfolding of the proteins in the presence of urea as the causes of the observed heterogeneity."}
{"id": "PMID:188961", "title": "Hyperkalemia unresponsive to massive doses of aldosterone and renal tubular acidosis in a patient with chronic interstitial nephritis: clinical and experimental studies.", "content": "A unique 53-year-old male patient is described in whom aldosterone-refractory hyperkalemia and renal tubular acidosis/RTA/ was due to chronic interstitial nephritis associated with peritubular hyaline deposits in the distal nephron. Hyperkalemia was not caused by an adrenal disorder or acidosis and could not be abolished by interventions enhancing K clearance; saline infusions, high doses of furosemide, cortisone, cortisol, long-acting synthetic ACTH and excessive doses of aldosterone. Glucocorticoids induced a marked decrease in sodium excreting capacity probably by an action on the ascending limb of Henle's loop while aldosterone elicited a paradoxical natriuretic response by unknown mechanism. The results of our experimental studies carried out on the hyperkalemic RTA patient as well as on various control subjects and patients suggest 1. a specific defect in renal K excretion associated with decreased aldosterone responsiveness of the tubules presumably due to the peritubular pathology, and 2. a disturbance in the cellular regulation of K distribution between fluid compartments of unknown origin.", "contents": "Hyperkalemia unresponsive to massive doses of aldosterone and renal tubular acidosis in a patient with chronic interstitial nephritis: clinical and experimental studies. A unique 53-year-old male patient is described in whom aldosterone-refractory hyperkalemia and renal tubular acidosis/RTA/ was due to chronic interstitial nephritis associated with peritubular hyaline deposits in the distal nephron. Hyperkalemia was not caused by an adrenal disorder or acidosis and could not be abolished by interventions enhancing K clearance; saline infusions, high doses of furosemide, cortisone, cortisol, long-acting synthetic ACTH and excessive doses of aldosterone. Glucocorticoids induced a marked decrease in sodium excreting capacity probably by an action on the ascending limb of Henle's loop while aldosterone elicited a paradoxical natriuretic response by unknown mechanism. The results of our experimental studies carried out on the hyperkalemic RTA patient as well as on various control subjects and patients suggest 1. a specific defect in renal K excretion associated with decreased aldosterone responsiveness of the tubules presumably due to the peritubular pathology, and 2. a disturbance in the cellular regulation of K distribution between fluid compartments of unknown origin."}
{"id": "PMID:188963", "title": "Output of oestrogens, testosterone and their precursors by isolated human adrenal cells as compared with that of glucocorticosteroids.", "content": "The output of oestrogens, testosterone and their precursors was compared with that of glucocorticosteroids under standardized conditions, in a suspension of isolated human adrenal cells. Cortisol, corticosterone, androstenedione, dehydroepiandrosterone and its sulphate all increased in the same proportions after ACTH stimulation. The response to the logarithm of ACTH concentrations had a sigmoid shape but was fairly linear between 5 and 100 to 1000 muu./ml. The output of dehydroepiandrosterone plus that of its sulphate was of the same order of magnitude as the production of cortisol; the output of free dehydroepiandrosterone averaged half that of the sulphate indicating that the adrenal cortex is capable, under certain conditions, of producing large amounts of the free steroid. The output of androstenedione was very low, on average 35 times lower than that of cortisol, suggesting by extrapolation that the adrenal secretion may not be the main source of androstenedione in vivo or that ACTH is not the unique stimulus to adrenal androstenedione secretion. The output of testosterone was small to negligible and that of oestrogens was practically absent. In three additional experiments the influence of prolactin, prostaglandins, FSH and HCG was explored: no selective stimulation of androgen or oestrogen output was observed except in one experiment in which HCG stimulated adrenal testosterone production.", "contents": "Output of oestrogens, testosterone and their precursors by isolated human adrenal cells as compared with that of glucocorticosteroids. The output of oestrogens, testosterone and their precursors was compared with that of glucocorticosteroids under standardized conditions, in a suspension of isolated human adrenal cells. Cortisol, corticosterone, androstenedione, dehydroepiandrosterone and its sulphate all increased in the same proportions after ACTH stimulation. The response to the logarithm of ACTH concentrations had a sigmoid shape but was fairly linear between 5 and 100 to 1000 muu./ml. The output of dehydroepiandrosterone plus that of its sulphate was of the same order of magnitude as the production of cortisol; the output of free dehydroepiandrosterone averaged half that of the sulphate indicating that the adrenal cortex is capable, under certain conditions, of producing large amounts of the free steroid. The output of androstenedione was very low, on average 35 times lower than that of cortisol, suggesting by extrapolation that the adrenal secretion may not be the main source of androstenedione in vivo or that ACTH is not the unique stimulus to adrenal androstenedione secretion. The output of testosterone was small to negligible and that of oestrogens was practically absent. In three additional experiments the influence of prolactin, prostaglandins, FSH and HCG was explored: no selective stimulation of androgen or oestrogen output was observed except in one experiment in which HCG stimulated adrenal testosterone production."}
{"id": "PMID:188964", "title": "Testosterone secretion by foetal rat testes in vitro.", "content": "Testosterone secretion by foetal rat testes (13 1/2-21 1/2 days of gestation) explanted for 3 days in a synthetic medium was measured every 24 h by radioimmunoassay. During the first day of explantation, the foetal testis produced, respectively, 1013 +/- 132, 8734 +/- 1118, 9179 +/- 2185 and 3886 +/- 309 (S.E.M.) pg/testis when explanted at 14 1/2, 16 1/2, 18 1/2 and 21 1/2 days respectively. Testosterone production by 13 1/2-day-old testes was not detectable on the first day of culture, but appeared on subsequent days. Daily testosterone secretion increased on the 2nd and 3rd days of culture in 14 1/2-day-old testes and decreased in older stages. These results suggest that the functional differentiation of the testis is independent of stimulatory factors like gonadotrophins. Dibutyryl cyclic AMP was found to stimulate testosterone production significantly from 14 1/2 days of gestation onwards.", "contents": "Testosterone secretion by foetal rat testes in vitro. Testosterone secretion by foetal rat testes (13 1/2-21 1/2 days of gestation) explanted for 3 days in a synthetic medium was measured every 24 h by radioimmunoassay. During the first day of explantation, the foetal testis produced, respectively, 1013 +/- 132, 8734 +/- 1118, 9179 +/- 2185 and 3886 +/- 309 (S.E.M.) pg/testis when explanted at 14 1/2, 16 1/2, 18 1/2 and 21 1/2 days respectively. Testosterone production by 13 1/2-day-old testes was not detectable on the first day of culture, but appeared on subsequent days. Daily testosterone secretion increased on the 2nd and 3rd days of culture in 14 1/2-day-old testes and decreased in older stages. These results suggest that the functional differentiation of the testis is independent of stimulatory factors like gonadotrophins. Dibutyryl cyclic AMP was found to stimulate testosterone production significantly from 14 1/2 days of gestation onwards."}
{"id": "PMID:188965", "title": "Adrenocortical function in a prototherian mammal, Tachyglossus aculeatus (Shaw).", "content": "The peripheral plasma concentrations and production rates of corticosterone and cortisol were measured in the conscious, unrestrained echidna (Tachyglossus aculeatus) under basal conditions and during maximal ACTH stimulation. Using Sephadex LH-20 column chromatography and radioligand assay, only cortisol and corticosterone could be detected in the peripheral blood plasma at very low concentrations of 0-07 +/- 0-03 (S.E.M.) mug/100 ml and 0-14 +/- 0-07 mug/100 ml respectively. Two-hourly sampling over periods of 36-48 h disclosed a diurnal periodicity in the combined plasma concentration of these corticosteroids, the high concentrations corresponding to periods of behavioural activity. Marked, short-term fluctuations in plasma corticosteroid concentration were also observed during periods of more frequent (20 min) sampling. Constant rate i.v. infusion of synthetic ACTH increased the plasma concentrations of both steroids to maximal values of 0-42 +/- 0-23 mug cortisol/100 ml and 1-06 +/- 0-56 mug corticosterone/100 ml at infusion rates of 1 i.u. ACTH/kg/h. This is approximately 1/160 of the potency of this ACTH in man. The production rates of corticosterone and cortisol, measured by isotope dilution during constant rate i.v. infusion of 3H-labelled tracers, were only 0-35 +/- 0-21 and 0-56 +/- 0-26 mug/kg/h respectively during saline infusion, and increased to 2-86 +/- 3-47 and 2-74 +/- 2-07 mug/kg/h during the infusion of 1 i.u. ACTH/kg/h. The metabolic clearance rate of cortisol was greater than that of corticosterone and both were depressed by ACTH. Plasma corticosteroid concentrations were increased after surgery during ether anaesthesia and in sick animals with heavy worm infestation. It is concluded that the adrenal cortex of echidnas responds to ACTH stimulation and stress in a similar way to eutherians, but the level of activity is much lower.", "contents": "Adrenocortical function in a prototherian mammal, Tachyglossus aculeatus (Shaw). The peripheral plasma concentrations and production rates of corticosterone and cortisol were measured in the conscious, unrestrained echidna (Tachyglossus aculeatus) under basal conditions and during maximal ACTH stimulation. Using Sephadex LH-20 column chromatography and radioligand assay, only cortisol and corticosterone could be detected in the peripheral blood plasma at very low concentrations of 0-07 +/- 0-03 (S.E.M.) mug/100 ml and 0-14 +/- 0-07 mug/100 ml respectively. Two-hourly sampling over periods of 36-48 h disclosed a diurnal periodicity in the combined plasma concentration of these corticosteroids, the high concentrations corresponding to periods of behavioural activity. Marked, short-term fluctuations in plasma corticosteroid concentration were also observed during periods of more frequent (20 min) sampling. Constant rate i.v. infusion of synthetic ACTH increased the plasma concentrations of both steroids to maximal values of 0-42 +/- 0-23 mug cortisol/100 ml and 1-06 +/- 0-56 mug corticosterone/100 ml at infusion rates of 1 i.u. ACTH/kg/h. This is approximately 1/160 of the potency of this ACTH in man. The production rates of corticosterone and cortisol, measured by isotope dilution during constant rate i.v. infusion of 3H-labelled tracers, were only 0-35 +/- 0-21 and 0-56 +/- 0-26 mug/kg/h respectively during saline infusion, and increased to 2-86 +/- 3-47 and 2-74 +/- 2-07 mug/kg/h during the infusion of 1 i.u. ACTH/kg/h. The metabolic clearance rate of cortisol was greater than that of corticosterone and both were depressed by ACTH. Plasma corticosteroid concentrations were increased after surgery during ether anaesthesia and in sick animals with heavy worm infestation. It is concluded that the adrenal cortex of echidnas responds to ACTH stimulation and stress in a similar way to eutherians, but the level of activity is much lower."}
{"id": "PMID:188966", "title": "Oestrogen-induced uterine protein: presence of associated phosphoprotein phosphatase activity before oestrogen treatment.", "content": "The phosphoprotein phosphatase (PPPase) activity that is found associated with oestrogen-induced protein(s) is not itself induced by oestrogen. Indeed, this activity was found at the same electrophoretic position (i.e. the position of the oestrogen-induced protein) and in equal amounts relative to the total PPPase activity, whether the cytosol fraction from control or from stimulated uteri was tested.", "contents": "Oestrogen-induced uterine protein: presence of associated phosphoprotein phosphatase activity before oestrogen treatment. The phosphoprotein phosphatase (PPPase) activity that is found associated with oestrogen-induced protein(s) is not itself induced by oestrogen. Indeed, this activity was found at the same electrophoretic position (i.e. the position of the oestrogen-induced protein) and in equal amounts relative to the total PPPase activity, whether the cytosol fraction from control or from stimulated uteri was tested."}
{"id": "PMID:188967", "title": "In-vitro studies of normal human thyroid cells: responses to thyrotrophin and dibutyryl cyclic AMP.", "content": "Follicular cells isolated from normal human thyroid tissue have been cultured for up to 140 h with bovine thyrotrophin (TSH) or dibutyryl cyclic AMP (DBcAMP). Both compounds induced marked reorganization of the cells into three-dimensional follicular structures, whilst non-supplemented cells assumed a monolayer form. Cultures treated initially with TSH or DBcAMP showed a greater iodide uptake capacity, in comparison with unsupplemented cultures, in which iodide uptake was markedly diminished after 24 h. The release of tri-iodothyronine (T3) and thyroxine (T4) into the medium was determined by radioimmunoassay. Both TSH- and DBcAMP-treated cells showed a significant increase in iodothyronine output compared with unsupplemented control cells. In contrast to the \"classical\" TSH-induced depression of the T4:T3 ratio in vivo, an increase in the ratio was observed for both TSH- and DBcAMP-supplemented cells in vitro. The ratio was also significantly greater after TSH than after DBcAMP, and possible implications of this findings are discussed.", "contents": "In-vitro studies of normal human thyroid cells: responses to thyrotrophin and dibutyryl cyclic AMP. Follicular cells isolated from normal human thyroid tissue have been cultured for up to 140 h with bovine thyrotrophin (TSH) or dibutyryl cyclic AMP (DBcAMP). Both compounds induced marked reorganization of the cells into three-dimensional follicular structures, whilst non-supplemented cells assumed a monolayer form. Cultures treated initially with TSH or DBcAMP showed a greater iodide uptake capacity, in comparison with unsupplemented cultures, in which iodide uptake was markedly diminished after 24 h. The release of tri-iodothyronine (T3) and thyroxine (T4) into the medium was determined by radioimmunoassay. Both TSH- and DBcAMP-treated cells showed a significant increase in iodothyronine output compared with unsupplemented control cells. In contrast to the \"classical\" TSH-induced depression of the T4:T3 ratio in vivo, an increase in the ratio was observed for both TSH- and DBcAMP-supplemented cells in vitro. The ratio was also significantly greater after TSH than after DBcAMP, and possible implications of this findings are discussed."}
{"id": "PMID:188969", "title": "The structure of the mitochondrial cloud of Xenopus laevis oocytes.", "content": "The ultrastructure of the mitochondrial cloud (Balbiani body) of the pre-vitellogenic oocytes of Xenopus laevis has been examined using transmission and stereoscan electron microscopy. Examination of conventional thin sections confirm previous observations which suggest that the cloud consists essentially of many thousands mitochondria and numerous small vesicles; larger clouds, in oocytes greater than 200 mum in diameter, contain relatively more vesicles. Using a standard electron microscope at 100 kV very long and coursing arrays of mitochondrial profiles can be detected. The presence of very long mitochondrial elements has been confirmed using a high voltage microscope operating at 500-1000 kV. Stereoscan preparations, isolated from pre-vitellogenic oocytes, lend some support to the view that the mitochondrial cloud amy consist of a mass of long filamentous mitochondria and the possibility that there are large continuous regions of mitochondrial material cannot be ruled out.", "contents": "The structure of the mitochondrial cloud of Xenopus laevis oocytes. The ultrastructure of the mitochondrial cloud (Balbiani body) of the pre-vitellogenic oocytes of Xenopus laevis has been examined using transmission and stereoscan electron microscopy. Examination of conventional thin sections confirm previous observations which suggest that the cloud consists essentially of many thousands mitochondria and numerous small vesicles; larger clouds, in oocytes greater than 200 mum in diameter, contain relatively more vesicles. Using a standard electron microscope at 100 kV very long and coursing arrays of mitochondrial profiles can be detected. The presence of very long mitochondrial elements has been confirmed using a high voltage microscope operating at 500-1000 kV. Stereoscan preparations, isolated from pre-vitellogenic oocytes, lend some support to the view that the mitochondrial cloud amy consist of a mass of long filamentous mitochondria and the possibility that there are large continuous regions of mitochondrial material cannot be ruled out."}
{"id": "PMID:188970", "title": "Complement-mediated antiserum cytotoxic reactions to human chromosome 7 coded antigen(s): immunoselection of rearranged human chromosome 7 in human-mouse somatic cell hybrids.", "content": "Immunoselection via complement-dependent lysis of human-mouse somatic cell hybrids containing chromosome 7, with antisera reactive to cell surface antigen(s) coded for by chromosome 7, has resulted in growth of somatic cell hybrids containing rearranged human chromosome 7s. Investigation of these hybrids has localized the gene(s) coding for the relevant cell surface antigen(s) to the short arm of human chromosome 7. The simian virus 40 integration site and the gene coding for human beta-glucuronidase appear to be localized to the long arm of chromosome 7 in this hybrid clone.", "contents": "Complement-mediated antiserum cytotoxic reactions to human chromosome 7 coded antigen(s): immunoselection of rearranged human chromosome 7 in human-mouse somatic cell hybrids. Immunoselection via complement-dependent lysis of human-mouse somatic cell hybrids containing chromosome 7, with antisera reactive to cell surface antigen(s) coded for by chromosome 7, has resulted in growth of somatic cell hybrids containing rearranged human chromosome 7s. Investigation of these hybrids has localized the gene(s) coding for the relevant cell surface antigen(s) to the short arm of human chromosome 7. The simian virus 40 integration site and the gene coding for human beta-glucuronidase appear to be localized to the long arm of chromosome 7 in this hybrid clone."}
{"id": "PMID:188971", "title": "Thymus-like activities of sulphur derivatives on T-cell differentiation.", "content": "Levamisole and sodium diethyldithiocarbamate can induce in vivo thymocyte differentiation from precursor spleen cells of nu/nu mice and evoke indirect plaque-forming cells in nude mice immunized with sheep red cells. These sulphur drugs induce in thymusless mice the production of a serum factor which transfer in vivo immune enhancement and in vitro thymocyte differentiation. In vivo treatment with sulphur derivative can substitute for an alleged thymice hormone.", "contents": "Thymus-like activities of sulphur derivatives on T-cell differentiation. Levamisole and sodium diethyldithiocarbamate can induce in vivo thymocyte differentiation from precursor spleen cells of nu/nu mice and evoke indirect plaque-forming cells in nude mice immunized with sheep red cells. These sulphur drugs induce in thymusless mice the production of a serum factor which transfer in vivo immune enhancement and in vitro thymocyte differentiation. In vivo treatment with sulphur derivative can substitute for an alleged thymice hormone."}
{"id": "PMID:188973", "title": "Plasmid modification of radiation and chemical-mutagen sensitivity in Pseudomonas aeruginosa.", "content": "The R factor pMG2 protects Pseudomonas aeruginosa against the lethal effects of ultraviolet (u.v.) and gamma irradiation, and methyl methanesulphonate and N-methyl-N'-nitro-N-nitrosoguanidine treatment. Enhanced survival occurs in strains of uvr+ rec+ (wild-type) genotype and a variety of uvr rec+ type mutants. No protection occurs in a rec A-type mutant. The plasmid also enhances u.v.-induced mutagenesis. These effects appear to be due to host-cell controlled plasmid-determined DNA repair function(s). Studies on P. aeruginosa strains deficient in DNA polymerase I (polyA) suggest that a plasmid-determined repair resynthesis function may be responsible for increased u.v.-survival and enhanced u.v.-mutability in pMG2-containing bacteria.", "contents": "Plasmid modification of radiation and chemical-mutagen sensitivity in Pseudomonas aeruginosa. The R factor pMG2 protects Pseudomonas aeruginosa against the lethal effects of ultraviolet (u.v.) and gamma irradiation, and methyl methanesulphonate and N-methyl-N'-nitro-N-nitrosoguanidine treatment. Enhanced survival occurs in strains of uvr+ rec+ (wild-type) genotype and a variety of uvr rec+ type mutants. No protection occurs in a rec A-type mutant. The plasmid also enhances u.v.-induced mutagenesis. These effects appear to be due to host-cell controlled plasmid-determined DNA repair function(s). Studies on P. aeruginosa strains deficient in DNA polymerase I (polyA) suggest that a plasmid-determined repair resynthesis function may be responsible for increased u.v.-survival and enhanced u.v.-mutability in pMG2-containing bacteria."}
{"id": "PMID:188975", "title": "Vesicular stomatitis virus: mode of transcription.", "content": "Recent studies on the mechanism by which the virion-associated RNA polymerase of vesicular stomatitis virus transcribes RNA have revealed several new biological features of general interest. The mode of synthesis of the 5'-terminal cap structure of the mRNAs, the sequential transcription of the genes and the presence of a transcribed \"leader\" RNA segment are properties which are either not shown by other viruses, or have not yet been described. These features are probably inter-related with the primary transcription process, which itself may be a useful model for future studies on mRNA biosynthesis in eukaryotic systems.", "contents": "Vesicular stomatitis virus: mode of transcription. Recent studies on the mechanism by which the virion-associated RNA polymerase of vesicular stomatitis virus transcribes RNA have revealed several new biological features of general interest. The mode of synthesis of the 5'-terminal cap structure of the mRNAs, the sequential transcription of the genes and the presence of a transcribed \"leader\" RNA segment are properties which are either not shown by other viruses, or have not yet been described. These features are probably inter-related with the primary transcription process, which itself may be a useful model for future studies on mRNA biosynthesis in eukaryotic systems."}
{"id": "PMID:188976", "title": "A morphological study of the M-protein of Sendai virus.", "content": "A purification scheme is described for the M-protein of Sendai virus and an electron microscope study of the isolated protein is presented. The protein exists as subunits of 6 nm in diam., which possess a central hole; the subunits may be dimers of the polypeptide. They are able to form filamentous aggregates which wind around one another to form a helical structure. It is suggested that these filaments may be the form adopted by the protein in the virus, the filaments lying parallel to one another just beneath the virus membrane to form a shell, but that the helical form is likely to be a property only of the isolated protein.", "contents": "A morphological study of the M-protein of Sendai virus. A purification scheme is described for the M-protein of Sendai virus and an electron microscope study of the isolated protein is presented. The protein exists as subunits of 6 nm in diam., which possess a central hole; the subunits may be dimers of the polypeptide. They are able to form filamentous aggregates which wind around one another to form a helical structure. It is suggested that these filaments may be the form adopted by the protein in the virus, the filaments lying parallel to one another just beneath the virus membrane to form a shell, but that the helical form is likely to be a property only of the isolated protein."}
{"id": "PMID:188977", "title": "Processing of a pseudorabies virus-induced protein which is glycosylated, sulphated and excreted.", "content": "Cells infected with pseudorabies virus excrete large amounts of a glycosylated sulphated protein, mol. wt. 89000, into the extracellular fluid. This paper reports the results of studies on the processing of this protein. Glycosylation occurs during, or very soon after, synthesis of the polypeptide chain. After a delay of several minutes the glycoprotein is sulphated; inhibition of glycosylation by high concentrations of glucosamine does not interfere with this process. The glycosylated sulphated polypeptide is then reduced in size from mol. wt. 99000 to 89000, possibly by proteolytic cleavage, and is excreted. Inhibition of glycosylation does not interfere with the excretion of this polypeptide, which is an energy-requiring process.", "contents": "Processing of a pseudorabies virus-induced protein which is glycosylated, sulphated and excreted. Cells infected with pseudorabies virus excrete large amounts of a glycosylated sulphated protein, mol. wt. 89000, into the extracellular fluid. This paper reports the results of studies on the processing of this protein. Glycosylation occurs during, or very soon after, synthesis of the polypeptide chain. After a delay of several minutes the glycoprotein is sulphated; inhibition of glycosylation by high concentrations of glucosamine does not interfere with this process. The glycosylated sulphated polypeptide is then reduced in size from mol. wt. 99000 to 89000, possibly by proteolytic cleavage, and is excreted. Inhibition of glycosylation does not interfere with the excretion of this polypeptide, which is an energy-requiring process."}
{"id": "PMID:188978", "title": "Aminoacylation of encephalomyocarditis virus RNA.", "content": "RNA extracted from purified encephalomyocarditis (EMC) virus (EMC-RNA) can be aminoacylated with synthetase praparations from Escherichia coli, beef and rabbit liver. The extent of aminoacylation is between 0-024 and 0-080 moles per mole EMC-RNA and occurs only with serine. Either removal of possible low mol. wt. contaminants with 3 M-sodium acetate nor periodate oxidation of the virus RNA affects its aminoacylation capacity.", "contents": "Aminoacylation of encephalomyocarditis virus RNA. RNA extracted from purified encephalomyocarditis (EMC) virus (EMC-RNA) can be aminoacylated with synthetase praparations from Escherichia coli, beef and rabbit liver. The extent of aminoacylation is between 0-024 and 0-080 moles per mole EMC-RNA and occurs only with serine. Either removal of possible low mol. wt. contaminants with 3 M-sodium acetate nor periodate oxidation of the virus RNA affects its aminoacylation capacity."}
{"id": "PMID:188979", "title": "A haemagglutination assay for the primate syncytium-forming (foamy) viruses.", "content": "Preparations of highly concentrated simian foamy virus type 1 (SFV1)agglutinate guinea pig red blood cells. The agglutination occurs both at 22 degrees and 37 degrees C. It is inhibited by specific antisera against SFV1 but also by antisera prepared against several other types of simian foamy viruses.", "contents": "A haemagglutination assay for the primate syncytium-forming (foamy) viruses. Preparations of highly concentrated simian foamy virus type 1 (SFV1)agglutinate guinea pig red blood cells. The agglutination occurs both at 22 degrees and 37 degrees C. It is inhibited by specific antisera against SFV1 but also by antisera prepared against several other types of simian foamy viruses."}
{"id": "PMID:188980", "title": "Effects of pyrimidine derivatives on RNA-dependent RNA polymerase of mengovirus-infected Fogh and Lund (FL) cells.", "content": "Two newly synthesized pyrimidine derivatives were found to possess antiviral activity against Mengovirus in Fogh and Lund (FL) cells and in a cell-free system. The inhibitory effect on RNA-dependent RNA polymerase of Mengovirus-infected FL cells was assayed using 14C-UTP as precursor. Addition of 50 or 100 muM of the inhibitors in a cell-free system of crude enzyme and nucleoside triphosphate medium for 60 min incubation at 37 degrees C resulted in about 40 to 60% lower counting rates for drug-treated reaction mixtures. The analysis of the polymerase synthesis product (virus RNA extracted from the cell-free reaction mixture and deproteinized by the phenol-SDS method) was carried out by means of agarose-acrylamide gel electrophoresis. The main finding was a reduction of single-stranded Mengovirus RNA (RNase-sensitive and LiCl-precipitable). The rates of synthesis of the replicative intermediate (LiCl-precipitable) and the replicative form of RNA (LiCl-soluble) were not significantly influenced.", "contents": "Effects of pyrimidine derivatives on RNA-dependent RNA polymerase of mengovirus-infected Fogh and Lund (FL) cells. Two newly synthesized pyrimidine derivatives were found to possess antiviral activity against Mengovirus in Fogh and Lund (FL) cells and in a cell-free system. The inhibitory effect on RNA-dependent RNA polymerase of Mengovirus-infected FL cells was assayed using 14C-UTP as precursor. Addition of 50 or 100 muM of the inhibitors in a cell-free system of crude enzyme and nucleoside triphosphate medium for 60 min incubation at 37 degrees C resulted in about 40 to 60% lower counting rates for drug-treated reaction mixtures. The analysis of the polymerase synthesis product (virus RNA extracted from the cell-free reaction mixture and deproteinized by the phenol-SDS method) was carried out by means of agarose-acrylamide gel electrophoresis. The main finding was a reduction of single-stranded Mengovirus RNA (RNase-sensitive and LiCl-precipitable). The rates of synthesis of the replicative intermediate (LiCl-precipitable) and the replicative form of RNA (LiCl-soluble) were not significantly influenced."}
{"id": "PMID:188981", "title": "Sequential immunofluorescence and infectivity studies on the replication of Herpesvirus saimiri in owl monkey kidney cells.", "content": "Methods are described for the preparation and authentication of a highly specific antiserum against herpesvirus saimiri (HVS) capsid antigens. The antiserum was used in immunofluorescence tests to follow the development of capsid antigens in HVS-infected owl monkey kidney cells throughout the virus replication cycle in parallel with sequential titrations of virus infectivity in both cells and medium. Fluorescence was detected as a round or oval, bright green area of staining at the centre of the nucleus which was similar in outline to the Cowdry type A inclusion seen in HVS-infected cells stained by haematoxylin and eosin. The first detection of fluorescence towards the end of the eclipse phase of the virus growth cycle, and its abolition by the treatment of infected cultures with cytosine arabinoside confirmed the identity of HVS capsid antigens as late antigens. The failure to detect fluorescence in the cytoplasm of HVS-infected cells has brought to light a conflict between the site of accumulation of virus capsid antigens as determined by immunofluorescence and the finding, by electron microscopy, of cytoplasmic immature particles in intact cells during the early stages of the virus replication cycle. The significance of this discrepancy is discussed in relation to its possible existence for other members of the herpesvirus group.", "contents": "Sequential immunofluorescence and infectivity studies on the replication of Herpesvirus saimiri in owl monkey kidney cells. Methods are described for the preparation and authentication of a highly specific antiserum against herpesvirus saimiri (HVS) capsid antigens. The antiserum was used in immunofluorescence tests to follow the development of capsid antigens in HVS-infected owl monkey kidney cells throughout the virus replication cycle in parallel with sequential titrations of virus infectivity in both cells and medium. Fluorescence was detected as a round or oval, bright green area of staining at the centre of the nucleus which was similar in outline to the Cowdry type A inclusion seen in HVS-infected cells stained by haematoxylin and eosin. The first detection of fluorescence towards the end of the eclipse phase of the virus growth cycle, and its abolition by the treatment of infected cultures with cytosine arabinoside confirmed the identity of HVS capsid antigens as late antigens. The failure to detect fluorescence in the cytoplasm of HVS-infected cells has brought to light a conflict between the site of accumulation of virus capsid antigens as determined by immunofluorescence and the finding, by electron microscopy, of cytoplasmic immature particles in intact cells during the early stages of the virus replication cycle. The significance of this discrepancy is discussed in relation to its possible existence for other members of the herpesvirus group."}
{"id": "PMID:188982", "title": "Protection of mice against encephalomyocarditis virus infection by preparations of transfer RNA.", "content": "Preparations of bacterial transfer RNA (tRNA), give dose-dependent protection of mice against encephalomyocarditis (EMC) virus infection at up to I mg tRNA per mouse with maximum response when the tRNA is administered around 6 h before infection. Protection occurs with intraperitoneally and intravenously administered tRNA against infections by both these routes. In some experiments significant protection occurs by single treatments of tRNA up to 24 h after infection with virus doses of I X LD100. Some tRNA preparations of eukaryotic origin do not give significant protection. Protection is not a feature of all species of bacterial tRNA; partially purified valine, tyrosine and phenylalanine tRNAs from Escherichia coli are not protective. tRNA treatment does not induce circulating interferon nor does it 'hypo-reactivate' the protective effect of poly (I).poly (C) treatment of mice. Humoral and cell mediated immune responses do not seem to be involved in tRNA mediated protection since first, cytosine arabinoside treatment does not affect protection by tRNA; second, serum from mice treated with tRNA and an EMC vaccine does not protect other mice against infection, and third, mice that survive normally lethal infections as a result of tRNA treatment are generally just as susceptible to re-infection as previously untreated, uninfected mice. Silica treatment abolishes protection of mice by tRNA implying that macrophages are necessary. However, tRNA does not seem to act by clearance of virus particles since vaccination of mice by inactivated EMC virus is not affected by tRNA treatment. These results are considered in relation to the presence of a tRNA-like structure in EMC virus RNA and protection of mice by other single stranded polynucleotides.", "contents": "Protection of mice against encephalomyocarditis virus infection by preparations of transfer RNA. Preparations of bacterial transfer RNA (tRNA), give dose-dependent protection of mice against encephalomyocarditis (EMC) virus infection at up to I mg tRNA per mouse with maximum response when the tRNA is administered around 6 h before infection. Protection occurs with intraperitoneally and intravenously administered tRNA against infections by both these routes. In some experiments significant protection occurs by single treatments of tRNA up to 24 h after infection with virus doses of I X LD100. Some tRNA preparations of eukaryotic origin do not give significant protection. Protection is not a feature of all species of bacterial tRNA; partially purified valine, tyrosine and phenylalanine tRNAs from Escherichia coli are not protective. tRNA treatment does not induce circulating interferon nor does it 'hypo-reactivate' the protective effect of poly (I).poly (C) treatment of mice. Humoral and cell mediated immune responses do not seem to be involved in tRNA mediated protection since first, cytosine arabinoside treatment does not affect protection by tRNA; second, serum from mice treated with tRNA and an EMC vaccine does not protect other mice against infection, and third, mice that survive normally lethal infections as a result of tRNA treatment are generally just as susceptible to re-infection as previously untreated, uninfected mice. Silica treatment abolishes protection of mice by tRNA implying that macrophages are necessary. However, tRNA does not seem to act by clearance of virus particles since vaccination of mice by inactivated EMC virus is not affected by tRNA treatment. These results are considered in relation to the presence of a tRNA-like structure in EMC virus RNA and protection of mice by other single stranded polynucleotides."}
{"id": "PMID:188983", "title": "Biochemical analysis of a virulent and an avirulent strain of foot-and-mouth disease virus.", "content": "A comparison has been made of some of the serological and physicochemical properties of a virulent and an avirulent strain of foot-and-mouth disease virus, serotype SAT1. The avirulent strain (SAT1-82) was derived from the virulent strain (SAT1-7) by serial passage in BHK 21 cells. The viruses were indistinguishable in cross-neutralization tests. In immunodiffusion tests a clear spur line was obtained with the SAT1-82 antiserum but not with SAT1-7 antiserum. The major polypeptides of the two viruses were identical when examined by polyacrylamide gel electrophoresis. Hybridization and thermal denaturation experiments failed to distinguish between the RNAs but two-dimensional electrophoresis of the oligonucleotides produced by ribonuclease T1 digestion revealed several differences. Possibly the most significant of these differences was the size of the polycytidylic acid [poly (C)] tract. There were about 170 nucleotides in the poly (C) tract of the SAT1-7 RNA compared with around 100 in the SAT1-82 RNA. Further evidence for this deletion was provided by the slightly different behaviour of the two RNAs when compared by sucrose gradient centrifugation and polyacrylamide gel electrophoresis.", "contents": "Biochemical analysis of a virulent and an avirulent strain of foot-and-mouth disease virus. A comparison has been made of some of the serological and physicochemical properties of a virulent and an avirulent strain of foot-and-mouth disease virus, serotype SAT1. The avirulent strain (SAT1-82) was derived from the virulent strain (SAT1-7) by serial passage in BHK 21 cells. The viruses were indistinguishable in cross-neutralization tests. In immunodiffusion tests a clear spur line was obtained with the SAT1-82 antiserum but not with SAT1-7 antiserum. The major polypeptides of the two viruses were identical when examined by polyacrylamide gel electrophoresis. Hybridization and thermal denaturation experiments failed to distinguish between the RNAs but two-dimensional electrophoresis of the oligonucleotides produced by ribonuclease T1 digestion revealed several differences. Possibly the most significant of these differences was the size of the polycytidylic acid [poly (C)] tract. There were about 170 nucleotides in the poly (C) tract of the SAT1-7 RNA compared with around 100 in the SAT1-82 RNA. Further evidence for this deletion was provided by the slightly different behaviour of the two RNAs when compared by sucrose gradient centrifugation and polyacrylamide gel electrophoresis."}
{"id": "PMID:188989", "title": "Method for quantitative estimation of thermal thresholds in patients.", "content": "A quantitative method for the examination of thermal sensibility was applied in 26 normal subjects and in patients with various neurological disorders. The stimulation technique resembled B\u00e9k\u00e9sy audiometry: the patient reversed the direction of the temperature change of a thermode whenever warm, cold, or thermal pain thresholds were reached. The resulting temperature curve enables a quantitative description of the subject's thermal sensibility and of the degree of impairment displayed by neurological patients.", "contents": "Method for quantitative estimation of thermal thresholds in patients. A quantitative method for the examination of thermal sensibility was applied in 26 normal subjects and in patients with various neurological disorders. The stimulation technique resembled B\u00e9k\u00e9sy audiometry: the patient reversed the direction of the temperature change of a thermode whenever warm, cold, or thermal pain thresholds were reached. The resulting temperature curve enables a quantitative description of the subject's thermal sensibility and of the degree of impairment displayed by neurological patients."}
{"id": "PMID:188990", "title": "Dysautonomia in Parkinsonism: a clinicopathological study.", "content": "Necropsy studies were done on six patients with idiopathic paralysis agitans, one with multiple system atrophy including features of Parkinsonism, and one control. Autonomic functions had been evaluated during life to a varying degree. Intra-arterial blood pressure studies were carried out on two patients with paralysis agitans (cases 4 and 6) and the one with multiple system atrophy (case 7). Lewy bodies with or without cell loss were seen in the sympathetic ganglia of five cases of paralysis agitans. Three of these had orthostatic hypotension and the severity of the lesion approximately correlated with the degree of hypotension. It is concluded that the lesions of the sympathetic ganglia may play a major role in the production of orthostatic hypotension in idiopathic paralysis agitans.", "contents": "Dysautonomia in Parkinsonism: a clinicopathological study. Necropsy studies were done on six patients with idiopathic paralysis agitans, one with multiple system atrophy including features of Parkinsonism, and one control. Autonomic functions had been evaluated during life to a varying degree. Intra-arterial blood pressure studies were carried out on two patients with paralysis agitans (cases 4 and 6) and the one with multiple system atrophy (case 7). Lewy bodies with or without cell loss were seen in the sympathetic ganglia of five cases of paralysis agitans. Three of these had orthostatic hypotension and the severity of the lesion approximately correlated with the degree of hypotension. It is concluded that the lesions of the sympathetic ganglia may play a major role in the production of orthostatic hypotension in idiopathic paralysis agitans."}
{"id": "PMID:188991", "title": "Studies on cyclic AMP in different compartments of cerebrospinal fluid.", "content": "Adenosine 3', 5'-monophosphate (cAMP) was measured in the CSF of 42 patients undergoing radiological investigation, neurosurgical procedures, or investigation of hepatic coma. The concentration of cAMP was significantly higher in ventricular CSF than in lumbar CSF. Premedication with pentobarbitone plus promethazine increased cAMP in lumbar CSF. There was no difference in cAMP concentration in lumbar CSF obtained before or after injection of air or after the administration of diazepam during lumbar pneumoencephalography. Lumbar CSF cAMP concentration was significantly increased in patients in hepatic coma. The concentration of cAMP in the lateral ventricle was not affected by general anaesthesia or by the presence of a complete block of the aqueduct of Sylvius. There was no decrease in lumbar CSF cAMP in patients with a complete stenosis of the aqueduct of Sylvius, partial blocks of CSF flow at the cervical level, or a complete block at the lower thoracic level. The concentration of cisternal CSF cAMP was similar to that of lumbar CSF. These results suggest that (1) there is a ventriculolumbar gradient in the concentration of cAMP but of insufficient magnitude to be detected by mixing of lumbar and ventricular CSF during pneumoencephalography, (2) lumbar CSF cAMP concentration is not dependent on brain as a source of this nucleotide; the source of this nucleotide may be largely derived from the spinal cord, (3) premedication may affect the concentration of cAMP in lumbar CSF cAMP, (4) the formation of cAMP is unimpaired in hepatic coma.", "contents": "Studies on cyclic AMP in different compartments of cerebrospinal fluid. Adenosine 3', 5'-monophosphate (cAMP) was measured in the CSF of 42 patients undergoing radiological investigation, neurosurgical procedures, or investigation of hepatic coma. The concentration of cAMP was significantly higher in ventricular CSF than in lumbar CSF. Premedication with pentobarbitone plus promethazine increased cAMP in lumbar CSF. There was no difference in cAMP concentration in lumbar CSF obtained before or after injection of air or after the administration of diazepam during lumbar pneumoencephalography. Lumbar CSF cAMP concentration was significantly increased in patients in hepatic coma. The concentration of cAMP in the lateral ventricle was not affected by general anaesthesia or by the presence of a complete block of the aqueduct of Sylvius. There was no decrease in lumbar CSF cAMP in patients with a complete stenosis of the aqueduct of Sylvius, partial blocks of CSF flow at the cervical level, or a complete block at the lower thoracic level. The concentration of cisternal CSF cAMP was similar to that of lumbar CSF. These results suggest that (1) there is a ventriculolumbar gradient in the concentration of cAMP but of insufficient magnitude to be detected by mixing of lumbar and ventricular CSF during pneumoencephalography, (2) lumbar CSF cAMP concentration is not dependent on brain as a source of this nucleotide; the source of this nucleotide may be largely derived from the spinal cord, (3) premedication may affect the concentration of cAMP in lumbar CSF cAMP, (4) the formation of cAMP is unimpaired in hepatic coma."}
{"id": "PMID:188995", "title": "Anticonvulsant prolongation of survival in adult murine lymphocytic choriomeningitis. II. Ultrastructural observations of pathogenetic events.", "content": "Because previous ultrastructural studies of murine lymphocytic choriomeningitis (LCM) had revealed only mononuclear cell infiltration with no cytopathology of target cells in the choroid plexus, ependyma, and leptomeninges, diazepam treatment was used to prolong survival for characterization of late pathogenetic events. Mice which were treated with diazepam and sacrificed 8, 9, and 10 days after intracerebral inoculation with LCM virus showed an increasing amount of inflammatory infiltration into choroid plexuses, leptomeninges, Virchow-Robin spaces, and ependyma. Mononuclear cells, lymphocytes, and polymorphonuclear (PMN) leukocytes increased in number as compared with terminally infected mice sacrificed 7 days after inoculation. Ultrastructurally, choroidal epithelial cells showed cytopathological changes varying from dilated endoplasmic reticulum through necrosis. Greater numbers of PMN leukocytes, macrophages, and activated macrophages and fewer undifferentiated mononuclear cells were seen in choroid plexuses of the drug-treated survivors. Virions and larger, more numerous arenavirus inclusions were present in choroid plexus and ependyma. Ultrastructurally the leptomeningitis was characterized by large numbers of activated macrophages. Choroidal epithelial necrosis appears to be the in vivo correlate of T-cell-mediated cytotoxicity in vitro.", "contents": "Anticonvulsant prolongation of survival in adult murine lymphocytic choriomeningitis. II. Ultrastructural observations of pathogenetic events. Because previous ultrastructural studies of murine lymphocytic choriomeningitis (LCM) had revealed only mononuclear cell infiltration with no cytopathology of target cells in the choroid plexus, ependyma, and leptomeninges, diazepam treatment was used to prolong survival for characterization of late pathogenetic events. Mice which were treated with diazepam and sacrificed 8, 9, and 10 days after intracerebral inoculation with LCM virus showed an increasing amount of inflammatory infiltration into choroid plexuses, leptomeninges, Virchow-Robin spaces, and ependyma. Mononuclear cells, lymphocytes, and polymorphonuclear (PMN) leukocytes increased in number as compared with terminally infected mice sacrificed 7 days after inoculation. Ultrastructurally, choroidal epithelial cells showed cytopathological changes varying from dilated endoplasmic reticulum through necrosis. Greater numbers of PMN leukocytes, macrophages, and activated macrophages and fewer undifferentiated mononuclear cells were seen in choroid plexuses of the drug-treated survivors. Virions and larger, more numerous arenavirus inclusions were present in choroid plexus and ependyma. Ultrastructurally the leptomeningitis was characterized by large numbers of activated macrophages. Choroidal epithelial necrosis appears to be the in vivo correlate of T-cell-mediated cytotoxicity in vitro."}
{"id": "PMID:188996", "title": "The ethnic distribution of primary central nervous system tumors: AFIP, 1958 to 1970.", "content": "A retrospective ethnic study was made of 16,311 cases of primary central nervous system (CNS) tumors seen at the Armed Forces Institute of Pathology (AFIP), Washington, D.C., from 1958 to 1970. Results showed a considerably higher Caucasian:Negro (C:N) case ratio (13.7:1) than the C:N population ratio (8.4:1), indicating a higher relative frequency of primary CNS tumors in American Caucasians as compared to American Negroes. The glioma was significantly more frequent in Caucasians than in Negroes (p less than 0.005). In contrast, Negroes had an excess of the pituitary adenoma as compared to Caucasians (P less than 0.01). The proportional frequencies of the meningioma and the nerve sheath tumor were also higher in Negroes than in Caucasians. When this pattern of the tumor distribution of American Negroes was compared to that of African Negroes (a composite African series), the preponderance of the pituitary adenoma and the meningioma and the relative paucity of the glioma in the Negro race as compared to Caucasians were again confirmed. The differences in the relative frequency and the tumor distribution between American Negroes and Caucasians and the considerable similarity of the tumor distribution between American and African Negroes emphasize the importance of genetic factors in the development of at least some primary CNS tumors.", "contents": "The ethnic distribution of primary central nervous system tumors: AFIP, 1958 to 1970. A retrospective ethnic study was made of 16,311 cases of primary central nervous system (CNS) tumors seen at the Armed Forces Institute of Pathology (AFIP), Washington, D.C., from 1958 to 1970. Results showed a considerably higher Caucasian:Negro (C:N) case ratio (13.7:1) than the C:N population ratio (8.4:1), indicating a higher relative frequency of primary CNS tumors in American Caucasians as compared to American Negroes. The glioma was significantly more frequent in Caucasians than in Negroes (p less than 0.005). In contrast, Negroes had an excess of the pituitary adenoma as compared to Caucasians (P less than 0.01). The proportional frequencies of the meningioma and the nerve sheath tumor were also higher in Negroes than in Caucasians. When this pattern of the tumor distribution of American Negroes was compared to that of African Negroes (a composite African series), the preponderance of the pituitary adenoma and the meningioma and the relative paucity of the glioma in the Negro race as compared to Caucasians were again confirmed. The differences in the relative frequency and the tumor distribution between American Negroes and Caucasians and the considerable similarity of the tumor distribution between American and African Negroes emphasize the importance of genetic factors in the development of at least some primary CNS tumors."}
{"id": "PMID:188992", "title": "235 cases of excessive daytime sleepiness. Diagnosis and tentative classification.", "content": "A series of 235 consecutive patients refferred to the Stanford University Sleep Disorders Clinic with the complaint of excessive daytime sleepiness (EDS) were investigated extensively. A satisfactory final diagnosis involving a consistent syndrome or pathogenic process was made in all but 7 patients. In the course of this work a variety of tests, including prolonged polygraphic monitoring of multiple variables and CSF measurements before and after probenecid ingestion, were utilized. Different syndromes were confirmed (harmonious hypersomnia, subwakefulness syndrome); the definitions of others were clarified and extended (narcolepsy, drug dependency, periodic hypersomnia associated with menstruation, upper airway sleep apnea in children). Two new entities were tentatively identified (narcolepsy with sleep apnea, the neutral state syndrome). Narcolepsy and upper airway sleep apnea accounted for the majority of the cases (199). A strategic schema utilizing specific categories and frequency of occurrence in the case series is presented to improve the diagnosis of the complaint of excessive daytime sleepiness by the practicing physician. This case series was analysed in order to develop tentatively a meaningful nosology.", "contents": "235 cases of excessive daytime sleepiness. Diagnosis and tentative classification. A series of 235 consecutive patients refferred to the Stanford University Sleep Disorders Clinic with the complaint of excessive daytime sleepiness (EDS) were investigated extensively. A satisfactory final diagnosis involving a consistent syndrome or pathogenic process was made in all but 7 patients. In the course of this work a variety of tests, including prolonged polygraphic monitoring of multiple variables and CSF measurements before and after probenecid ingestion, were utilized. Different syndromes were confirmed (harmonious hypersomnia, subwakefulness syndrome); the definitions of others were clarified and extended (narcolepsy, drug dependency, periodic hypersomnia associated with menstruation, upper airway sleep apnea in children). Two new entities were tentatively identified (narcolepsy with sleep apnea, the neutral state syndrome). Narcolepsy and upper airway sleep apnea accounted for the majority of the cases (199). A strategic schema utilizing specific categories and frequency of occurrence in the case series is presented to improve the diagnosis of the complaint of excessive daytime sleepiness by the practicing physician. This case series was analysed in order to develop tentatively a meaningful nosology."}
{"id": "PMID:188997", "title": "Intracisternal A and bar-shaped particles in murine neuroblastoma C 1300.", "content": "Transplantable murine neuroblastoma C 1300 was studied ultrastructurally at varying time intervals ranging from 2 hours to 40 days before and after X-irradiation. Following X-irradiation, 2000 and 4000 rads in a single dose, the uniformly small tumor cells became progressively enlarged multinucleated and degenerated, starting at one to two days. At five to seven days, the uni- and multinucleated giant cells predominated over the small tumor cells, while the giant cells progressively disappeared therafter and the small tumor cells predominated over the giant cells at 10 to 14 days. The giant cells contained abundant subcellular organelles and the X-irradiated tumor cells apparently continued to produce the organelles until they degenerated. Two types of cytoplasmic particles, intracisternal A and bar-shaped, were observed in the tumor cells. The intracisternal A particles occurred in almost all non-irradiated tumor cells though their number varied considerably from cell to cell, while they were observed less frequently in the radiation-induced giant cells probably due to a dilution effect rather than an actual numerical decrease. The bar-shaped particles, hitherto undescribed in the neuroblastoma, were 23 nm in diameter, variable in length and occasionally tubular. They occurred only in degenerating cells regardless of X-irradiation but were encountered more frequently in irradiated tumors than in non-irradiated ones. It is suggested that they may represent an unknown degenerative product of cytoplasm and/or nucleus rather than virus particles, despite their morphological resemblance to certain virus particles.", "contents": "Intracisternal A and bar-shaped particles in murine neuroblastoma C 1300. Transplantable murine neuroblastoma C 1300 was studied ultrastructurally at varying time intervals ranging from 2 hours to 40 days before and after X-irradiation. Following X-irradiation, 2000 and 4000 rads in a single dose, the uniformly small tumor cells became progressively enlarged multinucleated and degenerated, starting at one to two days. At five to seven days, the uni- and multinucleated giant cells predominated over the small tumor cells, while the giant cells progressively disappeared therafter and the small tumor cells predominated over the giant cells at 10 to 14 days. The giant cells contained abundant subcellular organelles and the X-irradiated tumor cells apparently continued to produce the organelles until they degenerated. Two types of cytoplasmic particles, intracisternal A and bar-shaped, were observed in the tumor cells. The intracisternal A particles occurred in almost all non-irradiated tumor cells though their number varied considerably from cell to cell, while they were observed less frequently in the radiation-induced giant cells probably due to a dilution effect rather than an actual numerical decrease. The bar-shaped particles, hitherto undescribed in the neuroblastoma, were 23 nm in diameter, variable in length and occasionally tubular. They occurred only in degenerating cells regardless of X-irradiation but were encountered more frequently in irradiated tumors than in non-irradiated ones. It is suggested that they may represent an unknown degenerative product of cytoplasm and/or nucleus rather than virus particles, despite their morphological resemblance to certain virus particles."}
{"id": "PMID:188993", "title": "Elevated parainfluenza virus type 1 antibody in patients with subacute sclerosing panencephalitis.", "content": "Parainfluenza virus hemagglutination inhibition (HI) antibodies were determined 3 times in the sera of 9 patients with subacute sclerosiing panencephalitis (SSPE) and 20 healthy controls matched for age and place of residence. Serum antibody against parainfluenza virus type 1 was significantly elevated in SSPE patients as compared with controls, whereas antibodies against type 2 and 3 were found to be in normal ranges. Higher titres of parainfluenza virus type 1 antibody might depend on: (1) dual viral infection, (2) cross-reaction between antigens of SSPE virus and parainfluenza virus type 1, and (3) non-specific activation of latent virus type 1 genome. The latter explanation seems to be particularly interesting since the parainfluenza type 1 antibody titres remained constant despite the clinical progression. This finding is comparable to the elevated titres against Epstein-Barr virus of adenovirus which have been found occasionally in this disease.", "contents": "Elevated parainfluenza virus type 1 antibody in patients with subacute sclerosing panencephalitis. Parainfluenza virus hemagglutination inhibition (HI) antibodies were determined 3 times in the sera of 9 patients with subacute sclerosiing panencephalitis (SSPE) and 20 healthy controls matched for age and place of residence. Serum antibody against parainfluenza virus type 1 was significantly elevated in SSPE patients as compared with controls, whereas antibodies against type 2 and 3 were found to be in normal ranges. Higher titres of parainfluenza virus type 1 antibody might depend on: (1) dual viral infection, (2) cross-reaction between antigens of SSPE virus and parainfluenza virus type 1, and (3) non-specific activation of latent virus type 1 genome. The latter explanation seems to be particularly interesting since the parainfluenza type 1 antibody titres remained constant despite the clinical progression. This finding is comparable to the elevated titres against Epstein-Barr virus of adenovirus which have been found occasionally in this disease."}
{"id": "PMID:188998", "title": "Functional organization of catfish retina.", "content": "1. The basic organization of the biphasic (or concentric) receptive field is established in the bipolar cells as the result of an interaction between two signals, one local representing the activity of a small number of receptors, and the other integrating (19, 20) or global (28) coming from the S space or a lamina formed by the horizontal cells (8, 14, 22, 29). 2. Bipolar-ganglion cell pairs are segregated into two types; A (on center) and B (off center) pairs. A depolarization of a bipolar cell produces spike discharges from ganglion cells of the same type and a hyperpolarization depresses their discharges. I haven't detected any cross talk between the types A and B pairs. Bipolar and ganglion cells must be interfaced by the classical chemical synapses, the only such kind in the catfish retina. 3. Horizontal and type N neurons form two lateral transmission systems, one distal and the other proximal (19, 20). Signals in the lateral systems are shared by the two receptive-field types and are not excitatory or inhibitory in themselves; it is incumbent upon the postsynaptic neurons to decide the polarity of the synaptic transmission. The horizontal cell participates directly in the formation of biphasic receptive fields of bipolar cells by providing their surrounding, whereas type N neuron seems to modify the receptive-field organization established in the bipolar cells. 4. Type N neurons are amacrine cells because they do not produce spike discharges (2, 18, 21) and because they influence the activity of both A and B receptive fields. 5. The function of the type C neuron is as unique as its structure (21) and is not fully clear as yet. It is not a conventional amacrine cell as the type N appears to be, nor is it a classical ganglion cell which forms either a type A or B receptive field (2). 6. Type Y neurons are a class of ganglion cells which forms either a type A or B receptive field.", "contents": "Functional organization of catfish retina. 1. The basic organization of the biphasic (or concentric) receptive field is established in the bipolar cells as the result of an interaction between two signals, one local representing the activity of a small number of receptors, and the other integrating (19, 20) or global (28) coming from the S space or a lamina formed by the horizontal cells (8, 14, 22, 29). 2. Bipolar-ganglion cell pairs are segregated into two types; A (on center) and B (off center) pairs. A depolarization of a bipolar cell produces spike discharges from ganglion cells of the same type and a hyperpolarization depresses their discharges. I haven't detected any cross talk between the types A and B pairs. Bipolar and ganglion cells must be interfaced by the classical chemical synapses, the only such kind in the catfish retina. 3. Horizontal and type N neurons form two lateral transmission systems, one distal and the other proximal (19, 20). Signals in the lateral systems are shared by the two receptive-field types and are not excitatory or inhibitory in themselves; it is incumbent upon the postsynaptic neurons to decide the polarity of the synaptic transmission. The horizontal cell participates directly in the formation of biphasic receptive fields of bipolar cells by providing their surrounding, whereas type N neuron seems to modify the receptive-field organization established in the bipolar cells. 4. Type N neurons are amacrine cells because they do not produce spike discharges (2, 18, 21) and because they influence the activity of both A and B receptive fields. 5. The function of the type C neuron is as unique as its structure (21) and is not fully clear as yet. It is not a conventional amacrine cell as the type N appears to be, nor is it a classical ganglion cell which forms either a type A or B receptive field (2). 6. Type Y neurons are a class of ganglion cells which forms either a type A or B receptive field."}
{"id": "PMID:188994", "title": "Neuropathy in hepatic disorders. A clinical, electrophysiological and histopathological appraisal.", "content": "The present study deals with 30 patients with cirrhosis of the liver and 12 patients with infective hepatitis who were studied clinically, neurophysiologically and histopathologically for the presence of neuropathy. Simultaneously, 13 healthy individuals were evaluated as controls. Clinical evidence of neuropathy was found in 63.3% of the patients with hepatic cirrhosis and in 16.6% of the patients with infective hepatitis. In hepatic cirrhosis, the conduction velocities were abnormal in 33.3% and histopathological demyelination was found in 80% of the patients. In infective hepatitis, on the other hand, altered nerve conduction velocities were found in 41.6% and segmental demyelination in 75% of the patients. Our data reveal that peripheral nerve involvement is seen both in chronic and acute liver disorders. The neuropathy in hepatic cirrhosis is unrelated to diabetes, alchoholism or portacaval shunt and may be due to unknown metabolic abnormality or to toxins. In infective hepatitis, the neuropathy may either be due to some acute metabolic derangement or may be purely viral in origin.", "contents": "Neuropathy in hepatic disorders. A clinical, electrophysiological and histopathological appraisal. The present study deals with 30 patients with cirrhosis of the liver and 12 patients with infective hepatitis who were studied clinically, neurophysiologically and histopathologically for the presence of neuropathy. Simultaneously, 13 healthy individuals were evaluated as controls. Clinical evidence of neuropathy was found in 63.3% of the patients with hepatic cirrhosis and in 16.6% of the patients with infective hepatitis. In hepatic cirrhosis, the conduction velocities were abnormal in 33.3% and histopathological demyelination was found in 80% of the patients. In infective hepatitis, on the other hand, altered nerve conduction velocities were found in 41.6% and segmental demyelination in 75% of the patients. Our data reveal that peripheral nerve involvement is seen both in chronic and acute liver disorders. The neuropathy in hepatic cirrhosis is unrelated to diabetes, alchoholism or portacaval shunt and may be due to unknown metabolic abnormality or to toxins. In infective hepatitis, the neuropathy may either be due to some acute metabolic derangement or may be purely viral in origin."}
{"id": "PMID:189000", "title": "Physiological responses of human adults to foods containing phosphate additives.", "content": "An experiment was conducted to assess the physiological effects of a diet rich in foods cotaining phosphate additives. During a 4-week control period, eight adults were fed a balanced diet free of phosphate additives providing approximately 95 g protein 0.7 g Ca and 1.0 g P per day. During a subsequent 4-week period, food items containing phosphate additives were substituted for counterpart items devoid of added phosphates. This diet contained 0.7 g Ca and 2.1 g P per day. The introduction of foods containing phosphate additives was associated with intestinal distress, soft stools or mild diarrhea. These symptoms subsided in six subjects but occurred intermittently throughout the experimental period in the other two subjects. The high-phosphorus diet induced increases in serum phosphorus and urinary phosphorus and decreases in serum calcium and urinary calcium. Hydroxyproline excretion in the urine was increased and cyclic AMP excretion was elevated in six of the eight subjects. These changes are analogous to those seen in experimental animals fed high-phosphorus diets which were shown to be due to enhanced parathyroid activity (secondary hyperparathyroidism). The use of phosphate food additives is discussed with respect to their possible stimulating effect on adult bone resorption.", "contents": "Physiological responses of human adults to foods containing phosphate additives. An experiment was conducted to assess the physiological effects of a diet rich in foods cotaining phosphate additives. During a 4-week control period, eight adults were fed a balanced diet free of phosphate additives providing approximately 95 g protein 0.7 g Ca and 1.0 g P per day. During a subsequent 4-week period, food items containing phosphate additives were substituted for counterpart items devoid of added phosphates. This diet contained 0.7 g Ca and 2.1 g P per day. The introduction of foods containing phosphate additives was associated with intestinal distress, soft stools or mild diarrhea. These symptoms subsided in six subjects but occurred intermittently throughout the experimental period in the other two subjects. The high-phosphorus diet induced increases in serum phosphorus and urinary phosphorus and decreases in serum calcium and urinary calcium. Hydroxyproline excretion in the urine was increased and cyclic AMP excretion was elevated in six of the eight subjects. These changes are analogous to those seen in experimental animals fed high-phosphorus diets which were shown to be due to enhanced parathyroid activity (secondary hyperparathyroidism). The use of phosphate food additives is discussed with respect to their possible stimulating effect on adult bone resorption."}
{"id": "PMID:189001", "title": "Relative activities of some metabolites and analogs of cholecalciferol in stimulation of tibia ash weight in chicks otherwise deprived of vitamin D.", "content": "Nine metabolites and analogs of cholecalciferol (CC) were tested for ability to increase tibia ash weight in chicks otherwise deprived of vitamin D. All of the compounds promoted bone mineralization in a linear log dose-response relationship. The maximal response obtained for any compound was an approximate doubling in bone ash weight compared to vehicle-treated controls. Relative potencies, based upon the calculated ash weight doubling dose, were as follows: 1 alpha, 25-(OH)2-CC = 1 alpha-OH-CC greater than CC greater than 25-OH-CC greater than 24R, 25-(OH)2-CC = 1 alpha,24R, 25-(OH)3- CC greater than 5,6-trans-25-OH-CC greater than 1 alpha, 24S, 25- (OH)3-CC greater than 5,6-trans-CC greater than 24S, 25-(OH)2-CC.", "contents": "Relative activities of some metabolites and analogs of cholecalciferol in stimulation of tibia ash weight in chicks otherwise deprived of vitamin D. Nine metabolites and analogs of cholecalciferol (CC) were tested for ability to increase tibia ash weight in chicks otherwise deprived of vitamin D. All of the compounds promoted bone mineralization in a linear log dose-response relationship. The maximal response obtained for any compound was an approximate doubling in bone ash weight compared to vehicle-treated controls. Relative potencies, based upon the calculated ash weight doubling dose, were as follows: 1 alpha, 25-(OH)2-CC = 1 alpha-OH-CC greater than CC greater than 25-OH-CC greater than 24R, 25-(OH)2-CC = 1 alpha,24R, 25-(OH)3- CC greater than 5,6-trans-25-OH-CC greater than 1 alpha, 24S, 25- (OH)3-CC greater than 5,6-trans-CC greater than 24S, 25-(OH)2-CC."}
{"id": "PMID:189002", "title": "Partial characterization of molecular species of retinol-binding protein found in tubular proteinuria due to chronic cadmium poisoning in the rabbit.", "content": "A study was conducted to characterize the molecular species of retinol-binding protein (RBP) isolated from the urine of rabbits chronically poisoned with cadmium. The RBP species, identical with regard to both molecular size (approximately 20,000) and immunoreactivity, were separated into four fractions by means of polyacrylamide gel electrophoresis (PAGE), which yielded two holo-RBP (H2 and H1) and two apo-RBP (A2 and A1) species. The urinary excretion ratio of these fractions (H2 : H1 : A2 : A1) was found to be about 70 : 6 : 21 : 3. No distinct difference of amino acid composition between holo- and apo-RBP was observed. An additional species of apo-RBP (designated An) was also isolated from theaged holo-RBP (H2) by isoelectric focusing in gel. Using the separated molecular species of rabbit RBP as well as of human RBP, their interactions with human prealbumin (PA) were examined both by human PA-Sepharose affinity chromatography, and by gel filtration on Sephadex G-100 after in vitro incubation of the RBP with human PA. Purified rabbit holo-RBP exhibited almost the same binding ability to human PA as did human RBP. Retinol within RBP molecule enhanced the affinity to PA, resumably through the change of tertiary structure, although the presence of retinol was not essential for the protein-protein interaction.", "contents": "Partial characterization of molecular species of retinol-binding protein found in tubular proteinuria due to chronic cadmium poisoning in the rabbit. A study was conducted to characterize the molecular species of retinol-binding protein (RBP) isolated from the urine of rabbits chronically poisoned with cadmium. The RBP species, identical with regard to both molecular size (approximately 20,000) and immunoreactivity, were separated into four fractions by means of polyacrylamide gel electrophoresis (PAGE), which yielded two holo-RBP (H2 and H1) and two apo-RBP (A2 and A1) species. The urinary excretion ratio of these fractions (H2 : H1 : A2 : A1) was found to be about 70 : 6 : 21 : 3. No distinct difference of amino acid composition between holo- and apo-RBP was observed. An additional species of apo-RBP (designated An) was also isolated from theaged holo-RBP (H2) by isoelectric focusing in gel. Using the separated molecular species of rabbit RBP as well as of human RBP, their interactions with human prealbumin (PA) were examined both by human PA-Sepharose affinity chromatography, and by gel filtration on Sephadex G-100 after in vitro incubation of the RBP with human PA. Purified rabbit holo-RBP exhibited almost the same binding ability to human PA as did human RBP. Retinol within RBP molecule enhanced the affinity to PA, resumably through the change of tertiary structure, although the presence of retinol was not essential for the protein-protein interaction."}
{"id": "PMID:189003", "title": "Synthesis and biological activity of 5,6-trans-vitamin D3 in anephric rats.", "content": "A modified procedure for the purification of 5,6-trans-D3 from a reaction mixture of vitamin D3 with iodine and its biological activity in sham-operated and anephric rats are described. When a solution of vitamin D3 in n-hexane was reacted with small quantities of iodine under influence of visible light, the reaction mixture gave four or five spots, including vitamin D3 and 5,6-trans-D3, on a thin layer chromatogram. After purifying the mixture by alumina column chromatography, a colorless oil from the separated 5,6-trans-D3 fractions was crystallized from n-hexane and snow white crystalline 5,6-trans-D3 was obtained. The purification method was thought to be better than the previously reported methods (14-16) because it gave good yield without the procedure of esterification using expensive p-phenylazobenzoyl chloride. A dose of 25 mug of 5,6-trans-D3 obtained thus gave significant elevation on intestinal calcium transport in both sham-operated and anephric rats, whereas the dose did not give positive effects on serum calcium levels in anephric rats. Serum phosphorous levels were extremely elevated by nephrectomy, but in both sham-operated and anephric rats they were unaffected by the administration of 25 myg of 5,6-trans-D3.", "contents": "Synthesis and biological activity of 5,6-trans-vitamin D3 in anephric rats. A modified procedure for the purification of 5,6-trans-D3 from a reaction mixture of vitamin D3 with iodine and its biological activity in sham-operated and anephric rats are described. When a solution of vitamin D3 in n-hexane was reacted with small quantities of iodine under influence of visible light, the reaction mixture gave four or five spots, including vitamin D3 and 5,6-trans-D3, on a thin layer chromatogram. After purifying the mixture by alumina column chromatography, a colorless oil from the separated 5,6-trans-D3 fractions was crystallized from n-hexane and snow white crystalline 5,6-trans-D3 was obtained. The purification method was thought to be better than the previously reported methods (14-16) because it gave good yield without the procedure of esterification using expensive p-phenylazobenzoyl chloride. A dose of 25 mug of 5,6-trans-D3 obtained thus gave significant elevation on intestinal calcium transport in both sham-operated and anephric rats, whereas the dose did not give positive effects on serum calcium levels in anephric rats. Serum phosphorous levels were extremely elevated by nephrectomy, but in both sham-operated and anephric rats they were unaffected by the administration of 25 myg of 5,6-trans-D3."}
{"id": "PMID:189004", "title": "The effects of ascorbic acid on diphtheria toxin and intoxicated HeLa cells.", "content": "Ascorbic acid (vitamin C) prevented diphtheria toxin from inhibiting the incorporation of [U-14C]-alanine into trichloroacetic acid precipitable material in HeLa cells. Ascorbic acid did not exhibit an effect on the adenosine diphosphate-ribosylation of amino acyl transferase II nor did it separate fragment A from fragment B in \"nicked\" toxin. A non-specific reducing agent, para-methylaminophenol sulfate, exhibited an effect on HeLa cells very similar to the results of ascorbic acid. Citric acid, a tricarboxylic acid, had no effect on HeLa cells.", "contents": "The effects of ascorbic acid on diphtheria toxin and intoxicated HeLa cells. Ascorbic acid (vitamin C) prevented diphtheria toxin from inhibiting the incorporation of [U-14C]-alanine into trichloroacetic acid precipitable material in HeLa cells. Ascorbic acid did not exhibit an effect on the adenosine diphosphate-ribosylation of amino acyl transferase II nor did it separate fragment A from fragment B in \"nicked\" toxin. A non-specific reducing agent, para-methylaminophenol sulfate, exhibited an effect on HeLa cells very similar to the results of ascorbic acid. Citric acid, a tricarboxylic acid, had no effect on HeLa cells."}
{"id": "PMID:189005", "title": "An immunopathologic study of interstitial nephritis associated with experimental canine adenovirus infection.", "content": "The localisation of canine adenovirus in the renal tubules induces a marked cellular response in the interstitium. A number of mechanisms appear to be involved in the genesis of the lesions. Direct lytic damage to tubular epithelial cells by the virus is probably augmented by immunological factors. The production of local anti-viral antibody by plasma cells in the vicinity of virus-containing cells may result in the formation of toxic antigen-antibody complexes while the accumulation of large populations of macrophages suggests that cell-mediated hypersensitivity is also operative.", "contents": "An immunopathologic study of interstitial nephritis associated with experimental canine adenovirus infection. The localisation of canine adenovirus in the renal tubules induces a marked cellular response in the interstitium. A number of mechanisms appear to be involved in the genesis of the lesions. Direct lytic damage to tubular epithelial cells by the virus is probably augmented by immunological factors. The production of local anti-viral antibody by plasma cells in the vicinity of virus-containing cells may result in the formation of toxic antigen-antibody complexes while the accumulation of large populations of macrophages suggests that cell-mediated hypersensitivity is also operative."}
{"id": "PMID:189006", "title": "Differential effects of the isomers of tetramisole on adrenergic neurotransmission in cutaneous veins of dog.", "content": "Clinical observations indicate that dexamisole and levamisole, the isomers of tetramisole, cause mood elevation. Their effects on smooth muscle cells and adrenergic nerves were investigated in strips of dogs' saphenous veins. Dexamisole (2.5 X 10(-6) to 4 X 10(-5) M) augmented the contractile response to norepinephrine but depressed that to tyramine; cocaine inhibited the augmentation of the norepinephrine response. Levamisole (10(-5) M) did not alter the response to norepinephrine, but augmented that to tyramine. At 1.6 X 10(-4) M dexamisole, more than levamisole, depressed the responses to norepinephrine, tyramine and acetylcholine. Activation by K+ ions was not affected by the isomers. Preparations, incubated with 3H-norepinephrine, were mounted for superfusion, tension recording and determination of 3H-norepinephrine and metabolites in the superfusate. Dexamisole and levamisole augmented the 3H-norepinephrine overflow during nerve stimulation; levamisole decreased the efflux of deaminated metabolites. During tyramine-induced contractions, dexamisole depressed and levamisole augmented the efflux of 3H-norepinephrine; they reduced the appearance of metabolites. The increases in 3H-norepinephrine caused by the isomers during nerve stimulation were not seen after phenoxybenzamine. Dexamisole, more than levamisole, inhibited tissular uptake of 3H-norepinephrine. Levamisole, more than dexamisole, inhibited monoamine oxidase activity in vein homogenates. These interferences with release and disposition of norepinephrine may be related to the antidepressant properties of the tetramisole isomers.", "contents": "Differential effects of the isomers of tetramisole on adrenergic neurotransmission in cutaneous veins of dog. Clinical observations indicate that dexamisole and levamisole, the isomers of tetramisole, cause mood elevation. Their effects on smooth muscle cells and adrenergic nerves were investigated in strips of dogs' saphenous veins. Dexamisole (2.5 X 10(-6) to 4 X 10(-5) M) augmented the contractile response to norepinephrine but depressed that to tyramine; cocaine inhibited the augmentation of the norepinephrine response. Levamisole (10(-5) M) did not alter the response to norepinephrine, but augmented that to tyramine. At 1.6 X 10(-4) M dexamisole, more than levamisole, depressed the responses to norepinephrine, tyramine and acetylcholine. Activation by K+ ions was not affected by the isomers. Preparations, incubated with 3H-norepinephrine, were mounted for superfusion, tension recording and determination of 3H-norepinephrine and metabolites in the superfusate. Dexamisole and levamisole augmented the 3H-norepinephrine overflow during nerve stimulation; levamisole decreased the efflux of deaminated metabolites. During tyramine-induced contractions, dexamisole depressed and levamisole augmented the efflux of 3H-norepinephrine; they reduced the appearance of metabolites. The increases in 3H-norepinephrine caused by the isomers during nerve stimulation were not seen after phenoxybenzamine. Dexamisole, more than levamisole, inhibited tissular uptake of 3H-norepinephrine. Levamisole, more than dexamisole, inhibited monoamine oxidase activity in vein homogenates. These interferences with release and disposition of norepinephrine may be related to the antidepressant properties of the tetramisole isomers."}
{"id": "PMID:189007", "title": "The effect of tolbutamide on contractility and cyclic adenosine 3':5'-monophosphate concentration in the intact beating rat heart.", "content": "The effect of tolbutamide on contractility and the concentration of cyclic adenosine 3':5'-monophosphate (cyclic AMP) in ventricular muscle was examined in the intact beating rat heart. The hearts were perfused in a nonrecirculated (Langendorff) fashion. Bolus injections of tolbutamide caused an increase in cardiac contractility. This increase in contractility was markedly inhibited when bovine albumin (3 g/100 ml) was present in the perfusing fluid. The increase in contractility caused by tolbutamide was not preceded by or associated with any change in the concentration of cyclic AMP in the ventricular muscle. Further studies utilizing a simultaneous injection of norepinephrine and tolbutamide demonstrated no significant effect of this combination on the concentration of cardiac cylcic AMP produced by an injection of norepinephrine alone. Our findings suggest that in the intact beating rat heart the positive inotropic effect of tolbutamide is not mediated via an increase in the concentration of cardiac cyclic AMP and that tolbutamide does not significantly potentiate the effect of catecholamines on cardiac cyclic AMP concentration.", "contents": "The effect of tolbutamide on contractility and cyclic adenosine 3':5'-monophosphate concentration in the intact beating rat heart. The effect of tolbutamide on contractility and the concentration of cyclic adenosine 3':5'-monophosphate (cyclic AMP) in ventricular muscle was examined in the intact beating rat heart. The hearts were perfused in a nonrecirculated (Langendorff) fashion. Bolus injections of tolbutamide caused an increase in cardiac contractility. This increase in contractility was markedly inhibited when bovine albumin (3 g/100 ml) was present in the perfusing fluid. The increase in contractility caused by tolbutamide was not preceded by or associated with any change in the concentration of cyclic AMP in the ventricular muscle. Further studies utilizing a simultaneous injection of norepinephrine and tolbutamide demonstrated no significant effect of this combination on the concentration of cardiac cylcic AMP produced by an injection of norepinephrine alone. Our findings suggest that in the intact beating rat heart the positive inotropic effect of tolbutamide is not mediated via an increase in the concentration of cardiac cyclic AMP and that tolbutamide does not significantly potentiate the effect of catecholamines on cardiac cyclic AMP concentration."}
{"id": "PMID:189008", "title": "Effects of carbamazepine on the water permeability and short-circuit current of the urinary bladder of the toad and the response to vasopressin, adenosine 3',5'-cyclic phosphate and theophylline.", "content": "Carbamazepine has been reported to decrease urine output and increase urinary concentration in patients with diabetes insipidus. The effects of the drug on the osmotic water permeability of the bladder of the toad, Bufo marinus, were studied. Carbamazepine had no effect on osmotic water flow when present in the serosal or mucosal bathing media. The submaximal or maximal increase in osmotic water flow caused by vasopressin was inhibited by serosal carbamazepine concentrations as low as 0.01 mM. Higher concentrations of carbamazepine in the mucosal solution also inhibited the submaximal antidiuretic hormone (ADH) response. The response to 2 mM cyclic AMP was inhibited by 0.5 mM serosal carbamazepine. Carbamazepine did not affect the response to 20 mM theophylline. Significant inhibition of the ADH response occurred only after preincubation of the bladders with the drug for at least 1 hour. The inhibition was reversed by rinsing the drug from the bladders before ADH was added. The mechanism of action of carbamazepine in diabetes insipidus remains obscure. In the toad bladder, the drug neither directly increases osmotic water flow nor potentiates the response to vasopressin.", "contents": "Effects of carbamazepine on the water permeability and short-circuit current of the urinary bladder of the toad and the response to vasopressin, adenosine 3',5'-cyclic phosphate and theophylline. Carbamazepine has been reported to decrease urine output and increase urinary concentration in patients with diabetes insipidus. The effects of the drug on the osmotic water permeability of the bladder of the toad, Bufo marinus, were studied. Carbamazepine had no effect on osmotic water flow when present in the serosal or mucosal bathing media. The submaximal or maximal increase in osmotic water flow caused by vasopressin was inhibited by serosal carbamazepine concentrations as low as 0.01 mM. Higher concentrations of carbamazepine in the mucosal solution also inhibited the submaximal antidiuretic hormone (ADH) response. The response to 2 mM cyclic AMP was inhibited by 0.5 mM serosal carbamazepine. Carbamazepine did not affect the response to 20 mM theophylline. Significant inhibition of the ADH response occurred only after preincubation of the bladders with the drug for at least 1 hour. The inhibition was reversed by rinsing the drug from the bladders before ADH was added. The mechanism of action of carbamazepine in diabetes insipidus remains obscure. In the toad bladder, the drug neither directly increases osmotic water flow nor potentiates the response to vasopressin."}
{"id": "PMID:189009", "title": "Spontaneous subminature end-plate potentials in mouse diaphragm muscle: evidence for synchronous release.", "content": "1. Miniature end-plate potentials (min.e.p.p.s) were recorded from small muscle cells of mouse diaphragms. Min.e.p.p. amplitude histograms showed successive peaks which were integral multiples of the smallest peak. The smallest potentials (submin.e.p.p.s) averaged 0-3-0-6mV and the mean of the larger min.e.p.p.s averaged 3-7 mV, depending on the muscle cell diameter. There was a positive correlation between time-to-peak and min.e.p.p. amplitude. Time-to-peak of the submin.e.p.p.s fell slightly below the regression line through the larger min.e.p.p.s. 2. Sometimes min.e.p.p. amplitude distributions changed spontaneously such that the mean of the major mode min.e.p.p.s decreased twofold during which time the mean of the submin.e.p.p.s did not change. Spontaneous decreases were most pronounced during low frequencies of release (10/min) achieved at 32 degrees C. 3. Small changes in temperature (2 degrees C steps in the range 32-40 degrees C) greatly altered the number of peaks of min.e.p.p. amplitude histograms without noticeably changing the position of the submin.e.p.p. peak. At 32 degrees C submin.e.p.p.s composed 5-20% of the histograms and the amplitude of the major mode peak was twelve to fifteen-times that of the submin.e.p.p.s. Over-all bell-shaped distributions were obtained at 37 degrees C which showed up to eight peaks with the major peak at the fourth to sixth peak. Temperatures slightly above 37 degrees C gave a flat distribution with the mean amplitude at the third peak. Min.e.p.p. amplitude histograms were initially skewed (mostly small min.e.p.p.s) after a 40 degrees C heat challenge. 4. Two to eight-times the normal concentration of Ca2+ in the saline reversibly increased the min.e.p.p. frequency and also decreased the mean of the major mode min.e.p.p.s (two to nine-times) without noticeably changing the mean of the submin.e.p.p.s. 5. Botulinum toxin A, 10(5) X intraperitoneal median lethal dose (10(5)I.P.LD50)/ml., almost abolished min.e.p.p.s in 30-90 min. The relative proportion of submin.e.p.p.s increased and the mean of the major mode min.e.p.p.s usually did not change during the initial decrease in frequency. Major mode min.e.p.p.s essentially ceased after 200-1000 were generated and remaining min.e.p.p.s of some cells showed skewed distributions with three small peaks that were integral multiples of the submin.e.p.p. peak. Smaller min.e.p.p.s were more resistant to block than the larger min.e.p.p.s and, although frequencies were low, small min.e.p.p.s were recorded after 4 hr of botulinum toxin incubation. 6. Colchicine (5 X 10(-4)M) within minutes reduced the major mode min.e.p.p.s by half (mean of major peak reduced to sixth or seventh peak). Additional colchicine (10(-3)M reduced the major mode min.e.p.p. amplitude to a fifth of that of control (mean of major mode min.e.p.p.s at the third peak) with no change in position of the submin.e.p.p. peak. Min.e.p.p. amplitudes slowly recovered to half control values after washing. 7...", "contents": "Spontaneous subminature end-plate potentials in mouse diaphragm muscle: evidence for synchronous release. 1. Miniature end-plate potentials (min.e.p.p.s) were recorded from small muscle cells of mouse diaphragms. Min.e.p.p. amplitude histograms showed successive peaks which were integral multiples of the smallest peak. The smallest potentials (submin.e.p.p.s) averaged 0-3-0-6mV and the mean of the larger min.e.p.p.s averaged 3-7 mV, depending on the muscle cell diameter. There was a positive correlation between time-to-peak and min.e.p.p. amplitude. Time-to-peak of the submin.e.p.p.s fell slightly below the regression line through the larger min.e.p.p.s. 2. Sometimes min.e.p.p. amplitude distributions changed spontaneously such that the mean of the major mode min.e.p.p.s decreased twofold during which time the mean of the submin.e.p.p.s did not change. Spontaneous decreases were most pronounced during low frequencies of release (10/min) achieved at 32 degrees C. 3. Small changes in temperature (2 degrees C steps in the range 32-40 degrees C) greatly altered the number of peaks of min.e.p.p. amplitude histograms without noticeably changing the position of the submin.e.p.p. peak. At 32 degrees C submin.e.p.p.s composed 5-20% of the histograms and the amplitude of the major mode peak was twelve to fifteen-times that of the submin.e.p.p.s. Over-all bell-shaped distributions were obtained at 37 degrees C which showed up to eight peaks with the major peak at the fourth to sixth peak. Temperatures slightly above 37 degrees C gave a flat distribution with the mean amplitude at the third peak. Min.e.p.p. amplitude histograms were initially skewed (mostly small min.e.p.p.s) after a 40 degrees C heat challenge. 4. Two to eight-times the normal concentration of Ca2+ in the saline reversibly increased the min.e.p.p. frequency and also decreased the mean of the major mode min.e.p.p.s (two to nine-times) without noticeably changing the mean of the submin.e.p.p.s. 5. Botulinum toxin A, 10(5) X intraperitoneal median lethal dose (10(5)I.P.LD50)/ml., almost abolished min.e.p.p.s in 30-90 min. The relative proportion of submin.e.p.p.s increased and the mean of the major mode min.e.p.p.s usually did not change during the initial decrease in frequency. Major mode min.e.p.p.s essentially ceased after 200-1000 were generated and remaining min.e.p.p.s of some cells showed skewed distributions with three small peaks that were integral multiples of the submin.e.p.p. peak. Smaller min.e.p.p.s were more resistant to block than the larger min.e.p.p.s and, although frequencies were low, small min.e.p.p.s were recorded after 4 hr of botulinum toxin incubation. 6. Colchicine (5 X 10(-4)M) within minutes reduced the major mode min.e.p.p.s by half (mean of major peak reduced to sixth or seventh peak). Additional colchicine (10(-3)M reduced the major mode min.e.p.p. amplitude to a fifth of that of control (mean of major mode min.e.p.p.s at the third peak) with no change in position of the submin.e.p.p. peak. Min.e.p.p. amplitudes slowly recovered to half control values after washing. 7..."}
{"id": "PMID:189018", "title": "Community mental health nursing: a social network approach.", "content": "This paper describes an intervention technique that the psychiatric nurse may find useful in community mental health settings. This technique is called social network intervention. It attempts to combine the best of traditional clinical psychotherapeutic method with the advantages of a social systems approach for working with the patient in psychiatric distress. The technique is based on the assumption that the solution to a variety of human predicaments lies within the collective instrumental and affective resources of a patient's social network. The vehicle for accomplishing this is the \"Network Session\" during which a mental health clinician convenes the patient and his/her social network to help plan and resolve the difficulty. A Case Report demonstrating the use of the technique is included.", "contents": "Community mental health nursing: a social network approach. This paper describes an intervention technique that the psychiatric nurse may find useful in community mental health settings. This technique is called social network intervention. It attempts to combine the best of traditional clinical psychotherapeutic method with the advantages of a social systems approach for working with the patient in psychiatric distress. The technique is based on the assumption that the solution to a variety of human predicaments lies within the collective instrumental and affective resources of a patient's social network. The vehicle for accomplishing this is the \"Network Session\" during which a mental health clinician convenes the patient and his/her social network to help plan and resolve the difficulty. A Case Report demonstrating the use of the technique is included."}
{"id": "PMID:189021", "title": "[Results of concentrated irridiation in glioblastomas, astrocytomas and brain tumours of the adult (author's transl)].", "content": "Concentrated irradiation (two series of 1,800 rads in 2 sessions and 3 days) separated by a rest period of 3 to 4 weeks has been used to treat 214 adult patients with brain tumors between 1965 and 1972. These included 108 glioblastomas, 18 astrocytomas and 88 brain metastases from different origins. Early side effects are moderate or inexistent provided synthetic ACTH or corticoid steroids have been given several days before irradiation. Survival is related, at least, in the first 2 groups of primary tumor to local failure. For brain metastases, death could be related to others reasons. In spite of the fact that comparison is made with a previous series of 121 cases it seems that this type of irradiation gives the same survival rates. Moreover it has specific advantages as reducing duration of hospitalization and the number of treatment sessions.", "contents": "[Results of concentrated irridiation in glioblastomas, astrocytomas and brain tumours of the adult (author's transl)]. Concentrated irradiation (two series of 1,800 rads in 2 sessions and 3 days) separated by a rest period of 3 to 4 weeks has been used to treat 214 adult patients with brain tumors between 1965 and 1972. These included 108 glioblastomas, 18 astrocytomas and 88 brain metastases from different origins. Early side effects are moderate or inexistent provided synthetic ACTH or corticoid steroids have been given several days before irradiation. Survival is related, at least, in the first 2 groups of primary tumor to local failure. For brain metastases, death could be related to others reasons. In spite of the fact that comparison is made with a previous series of 121 cases it seems that this type of irradiation gives the same survival rates. Moreover it has specific advantages as reducing duration of hospitalization and the number of treatment sessions."}
{"id": "PMID:189023", "title": "[Interstitial pneumonia in the immunodepressed child (author's transl)].", "content": "The authors stress the value of radiological examinations in the diagnosis of interstitial pneumonia in children with immuno-depression secondary to chemotherapy and/or radiotherapy. X-rays play a capital role in the early diagnosis of these conditions and may be of vital interest in some cases, in particular pneumocystosis which is curable. The diagnosis is based upon the discovery of minor signs of radiological interstitial syndrome, which in one third of cases is limited to a decrease in lung volume. This syndrome will be associated sooner or later with signs of alveolar involvement. The authors subsequently describe the underlying background, frequency, immune state, the circumstances of diagnosis and features of the aetiological diagnosis.", "contents": "[Interstitial pneumonia in the immunodepressed child (author's transl)]. The authors stress the value of radiological examinations in the diagnosis of interstitial pneumonia in children with immuno-depression secondary to chemotherapy and/or radiotherapy. X-rays play a capital role in the early diagnosis of these conditions and may be of vital interest in some cases, in particular pneumocystosis which is curable. The diagnosis is based upon the discovery of minor signs of radiological interstitial syndrome, which in one third of cases is limited to a decrease in lung volume. This syndrome will be associated sooner or later with signs of alveolar involvement. The authors subsequently describe the underlying background, frequency, immune state, the circumstances of diagnosis and features of the aetiological diagnosis."}
{"id": "PMID:189024", "title": "The metalloenzymic nature of collagenase-like peptidase of the rat testis.", "content": "Collagenase-like peptidase, an enzyme degrading synthetic collagenase substrate (PZ-pentapeptide), was purified from rat testes and its properties were examined. Its activity was strongly inhibited by chelating agents, such as EDTA and 1,10-phenanthroline. By chelation and exhaustive dialysis it was possible to obtain this enzyme in its inactive, metal-free form. The activity of the metal-free enzyme was partly recovered by treatment with zinc or manganese ions, while a combined zinc and manganese treatment resulted in complete recovery of enzyme activity.", "contents": "The metalloenzymic nature of collagenase-like peptidase of the rat testis. Collagenase-like peptidase, an enzyme degrading synthetic collagenase substrate (PZ-pentapeptide), was purified from rat testes and its properties were examined. Its activity was strongly inhibited by chelating agents, such as EDTA and 1,10-phenanthroline. By chelation and exhaustive dialysis it was possible to obtain this enzyme in its inactive, metal-free form. The activity of the metal-free enzyme was partly recovered by treatment with zinc or manganese ions, while a combined zinc and manganese treatment resulted in complete recovery of enzyme activity."}
{"id": "PMID:189027", "title": "Amniogenic bands associated with facial dysplasia and paresis.", "content": "A case of the amniogenic band syndrome is described with typical digital constriction bands amputations and syndactyly. The amniotic bands were demonstrated macroscopically and histologically, thus establishing the diagnosis. Facial dysplasia and unilateral facial paresis were attributed to undefined mechanical effects following amniotic rupture. In addition, there was evidence of partial umbilical cord compression which did not appear to have affected fetal well-being.", "contents": "Amniogenic bands associated with facial dysplasia and paresis. A case of the amniogenic band syndrome is described with typical digital constriction bands amputations and syndactyly. The amniotic bands were demonstrated macroscopically and histologically, thus establishing the diagnosis. Facial dysplasia and unilateral facial paresis were attributed to undefined mechanical effects following amniotic rupture. In addition, there was evidence of partial umbilical cord compression which did not appear to have affected fetal well-being."}
{"id": "PMID:189028", "title": "11,12-Secoprostaglandins. 1. Acylhydroxyalkanoic acids and related compounds.", "content": "The synthesis is described of a series of acylhydroxyalkanoic acids which embody structural modifications of that class of secoprostaglandins which are formally derived from the natural substances by scission of the cyclopentane ring between carbon atoms 11 and 12. These analogues have been tested for their ability to stimulate cAMP formation in the mouse ovary, a characteristic action of the (E)-prostaglandins, and for their ability to bind to the rat lipocyte prostaglandin receptor. Certain members of the series that most closely resemble the prostaglandins in structure (e.g., 8-acetyl-12-hydroxyheptadecanoic acid) markedly stimulate cAMP formation at concentrations in the pharmacological range and show a significant affinity for the prostaglandin receptor. Conversely, these compounds are not substrates for prostaglandin 15-hydroxydehydrogenase which catalyzes a major reaction in the biological deactivation of the prostaglandins.", "contents": "11,12-Secoprostaglandins. 1. Acylhydroxyalkanoic acids and related compounds. The synthesis is described of a series of acylhydroxyalkanoic acids which embody structural modifications of that class of secoprostaglandins which are formally derived from the natural substances by scission of the cyclopentane ring between carbon atoms 11 and 12. These analogues have been tested for their ability to stimulate cAMP formation in the mouse ovary, a characteristic action of the (E)-prostaglandins, and for their ability to bind to the rat lipocyte prostaglandin receptor. Certain members of the series that most closely resemble the prostaglandins in structure (e.g., 8-acetyl-12-hydroxyheptadecanoic acid) markedly stimulate cAMP formation at concentrations in the pharmacological range and show a significant affinity for the prostaglandin receptor. Conversely, these compounds are not substrates for prostaglandin 15-hydroxydehydrogenase which catalyzes a major reaction in the biological deactivation of the prostaglandins."}
{"id": "PMID:189029", "title": "11,12-Secoprostaglandins. 2. N-acyl-N-alkyl-7-aminoheptanoic acids.", "content": "A series of N-acyl-N-alkyl-7-aminoheptanoic acids has been prepared and evaluated for their ability to mimic the natural prostaglandins in certain biological systems. These compounds can be regarded as 8-aza-11,12-secoprostaglandins and, indeed, most of them stimulate cAMP formation in the mouse ovary assay, just as is observed with the natural prostaglandins. Selected compounds from this series also have been studied and shown to have prostaglandin-like effects in vivo.", "contents": "11,12-Secoprostaglandins. 2. N-acyl-N-alkyl-7-aminoheptanoic acids. A series of N-acyl-N-alkyl-7-aminoheptanoic acids has been prepared and evaluated for their ability to mimic the natural prostaglandins in certain biological systems. These compounds can be regarded as 8-aza-11,12-secoprostaglandins and, indeed, most of them stimulate cAMP formation in the mouse ovary assay, just as is observed with the natural prostaglandins. Selected compounds from this series also have been studied and shown to have prostaglandin-like effects in vivo."}
{"id": "PMID:189030", "title": "Irreversible enzyme inhibitors. 200. Active-site-directed inhibitors of deoxycytidine kinase.", "content": "Forty-three pyrimidine derivatives, mainly containing the 4-aminopyrimidine system, have been prepared and evaluated as inhibitors of deoxycytidine kinase. The most effective inhibitors were 2-alkylthio-4-aminopyrimidines and 1-alky-1-cytosines. The best inhibitors in both groups were those with large alkyl substituents, which indicate that hydrophobic bonding is occurring, possibly in the same area adjacent to the active site.", "contents": "Irreversible enzyme inhibitors. 200. Active-site-directed inhibitors of deoxycytidine kinase. Forty-three pyrimidine derivatives, mainly containing the 4-aminopyrimidine system, have been prepared and evaluated as inhibitors of deoxycytidine kinase. The most effective inhibitors were 2-alkylthio-4-aminopyrimidines and 1-alky-1-cytosines. The best inhibitors in both groups were those with large alkyl substituents, which indicate that hydrophobic bonding is occurring, possibly in the same area adjacent to the active site."}
{"id": "PMID:189031", "title": "Inhibition of squalene synthetase by farnesyl pyrophosphate analogues.", "content": "The pyrophosphates of the following farnesol analogues have been synthesized: 2-methylfarnesol; 7,11-dimethyl-3-ethyl-2,6,10-dodecatrien-1-ol; 3-demethylfarnesol; 4-methylthiofarnesol; 7,11-dimethyl-3-iodo-2,6,10-dodecatrien-1-ol; 7,11-dimethyl02-iodo-2,6,10-dodecatrien-1-ol; 7,11-dimethyldodeca-6,10-dien-2-yn-1-ol; phytol; 3,7,11-trimethyl-2-dodecen-1-ol; 3,7,11-trimethyldodecan-1-ol; and geraniol. The double bonds in all the above compounds were in the E configuration, except phytol, which was a 7:3 mixture of 2E and 2Z isomers. Each of the pyrophosphates inhibits the incorporation of labeled farnesyl pyrophosphate into squalene by a yeast enzyme preparation. Free alcohols and monophosphates are inactive. The analogues, listed in order of decreasing inhibitory strength, are, by kinetic analysis, competitive or mixed inhibitors. Irreversible inhibition is not observed. The results suggest that binding to the enzyme is primarily mediated by the pyrophosphate moiety assisted by relatively nonspecific lipophilic interactions. Decreasing the chain length and saturating double bonds severely reduces binding, while substitution at the 2,3, and 4 positions, and lengthening of the chain, is well tolerated.", "contents": "Inhibition of squalene synthetase by farnesyl pyrophosphate analogues. The pyrophosphates of the following farnesol analogues have been synthesized: 2-methylfarnesol; 7,11-dimethyl-3-ethyl-2,6,10-dodecatrien-1-ol; 3-demethylfarnesol; 4-methylthiofarnesol; 7,11-dimethyl-3-iodo-2,6,10-dodecatrien-1-ol; 7,11-dimethyl02-iodo-2,6,10-dodecatrien-1-ol; 7,11-dimethyldodeca-6,10-dien-2-yn-1-ol; phytol; 3,7,11-trimethyl-2-dodecen-1-ol; 3,7,11-trimethyldodecan-1-ol; and geraniol. The double bonds in all the above compounds were in the E configuration, except phytol, which was a 7:3 mixture of 2E and 2Z isomers. Each of the pyrophosphates inhibits the incorporation of labeled farnesyl pyrophosphate into squalene by a yeast enzyme preparation. Free alcohols and monophosphates are inactive. The analogues, listed in order of decreasing inhibitory strength, are, by kinetic analysis, competitive or mixed inhibitors. Irreversible inhibition is not observed. The results suggest that binding to the enzyme is primarily mediated by the pyrophosphate moiety assisted by relatively nonspecific lipophilic interactions. Decreasing the chain length and saturating double bonds severely reduces binding, while substitution at the 2,3, and 4 positions, and lengthening of the chain, is well tolerated."}
{"id": "PMID:189032", "title": "Synthesis and antiviral activity of certain thiazole C-nucleosides.", "content": "A general reaction of glycosyl cyanides with liquid hydrogen sulfide in the presence of 4-dimethylaminopyridine to provide the corresponding glycosylthiocarboxamides is described. These glycosylthiocarboxamides were utilized as the precursors for the synthesis of 2-D-ribofuranosylthiazole-4-carboxamide and 2-beta-D-ribofuranosylthiazole-5-carboxamide (23). The structural modification of 2-beta-D-ribofuranosylthiazole-4-carboxamide (12) into 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)thiazole-4-carboxamide (15), 2-beta-D-ribofuranosylthiazole-4-thiocarboxamide (17), and 2-(5-deoxy-beta-D-ribofuranosyl)thiazole-4-carboxamide (19) is also described. These thiazole nucleosides were tested for in vitro activity against type 1 herpes virus, type 3 parainfluenza virus, and type 13 rhinovirus and an in vivo experiment was run against parainfluenza virus. They were also evaluated as potential inhibitors of purine nucleotide biosynthesis. It was shown that the compounds (12 and 15) which possessed the most significant antiviral activity were also active inhibitors (40-70%) of guanine nucleotide biosynthesis.", "contents": "Synthesis and antiviral activity of certain thiazole C-nucleosides. A general reaction of glycosyl cyanides with liquid hydrogen sulfide in the presence of 4-dimethylaminopyridine to provide the corresponding glycosylthiocarboxamides is described. These glycosylthiocarboxamides were utilized as the precursors for the synthesis of 2-D-ribofuranosylthiazole-4-carboxamide and 2-beta-D-ribofuranosylthiazole-5-carboxamide (23). The structural modification of 2-beta-D-ribofuranosylthiazole-4-carboxamide (12) into 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)thiazole-4-carboxamide (15), 2-beta-D-ribofuranosylthiazole-4-thiocarboxamide (17), and 2-(5-deoxy-beta-D-ribofuranosyl)thiazole-4-carboxamide (19) is also described. These thiazole nucleosides were tested for in vitro activity against type 1 herpes virus, type 3 parainfluenza virus, and type 13 rhinovirus and an in vivo experiment was run against parainfluenza virus. They were also evaluated as potential inhibitors of purine nucleotide biosynthesis. It was shown that the compounds (12 and 15) which possessed the most significant antiviral activity were also active inhibitors (40-70%) of guanine nucleotide biosynthesis."}
{"id": "PMID:189033", "title": "6-aminopyrazolo[4,3-c]pyridin-4(5H)-one, a novel analogue of guanine.", "content": "Treatment of dimethyl alpha-ethoxymethylidineacetonedicarboxylate with hydrazine gave methyl 3-(methoxy-carbonylmethyl)pyrazole-4-carboxylate which, upon ammonolysis and dehydration, afforded methyl 3-(cyanomethyl)pyrazole-4-carboxylate. This compound, when heated with liquid ammonia, gave 6-aminopyrazolo[4,3-c]pyridin-4(5H)-one, a new guanine analogue, which did not possess any of the potent antiviral activity shown by 6-aminoimidazo[4,5-c]pyridin-4(5H)-one (3-deazaguanine).", "contents": "6-aminopyrazolo[4,3-c]pyridin-4(5H)-one, a novel analogue of guanine. Treatment of dimethyl alpha-ethoxymethylidineacetonedicarboxylate with hydrazine gave methyl 3-(methoxy-carbonylmethyl)pyrazole-4-carboxylate which, upon ammonolysis and dehydration, afforded methyl 3-(cyanomethyl)pyrazole-4-carboxylate. This compound, when heated with liquid ammonia, gave 6-aminopyrazolo[4,3-c]pyridin-4(5H)-one, a new guanine analogue, which did not possess any of the potent antiviral activity shown by 6-aminoimidazo[4,5-c]pyridin-4(5H)-one (3-deazaguanine)."}
{"id": "PMID:189035", "title": "Intercellular communication and tissue growth: VII. A cancer cell strain with retarded formation of permeable membrane junction and reduced exchange of a 330-dalton molecule.", "content": "A cancer (hepatoma) cell strain is described in which the formation of junctional membrane channels is abnormally slow. The development of electrical junctional coupling following the establishment of contact between these (reaggregated) cells is at least 15 times slower than that between their normal counterparts; and junctional transfer of fluorescein eventually develops, but only in about 5 per cent of the contacts (as against 100 per cent normally). This deviant membrane behavior is interpreted as a retardation in the process of accretion of junctional membrane channels. Its possible etiological role in defective growth regulation is discussed.", "contents": "Intercellular communication and tissue growth: VII. A cancer cell strain with retarded formation of permeable membrane junction and reduced exchange of a 330-dalton molecule. A cancer (hepatoma) cell strain is described in which the formation of junctional membrane channels is abnormally slow. The development of electrical junctional coupling following the establishment of contact between these (reaggregated) cells is at least 15 times slower than that between their normal counterparts; and junctional transfer of fluorescein eventually develops, but only in about 5 per cent of the contacts (as against 100 per cent normally). This deviant membrane behavior is interpreted as a retardation in the process of accretion of junctional membrane channels. Its possible etiological role in defective growth regulation is discussed."}
{"id": "PMID:189037", "title": "Virus isolation test for feline leukemia virus.", "content": "A method was developed for detecting feline leukemia virus (FeLV) infection in cats by coculturing separated blood lymphocytes and platelets with clone 81 cells carrying a murine sarcoma genome but free of leukemia virus (S+L-). FeLV caused cell transformation that was easily visible 3-12 days after infection. This method is simple, sensitive, and easily read; it has the advantage of directly detecting infectious FeLV rather than viral antigens.", "contents": "Virus isolation test for feline leukemia virus. A method was developed for detecting feline leukemia virus (FeLV) infection in cats by coculturing separated blood lymphocytes and platelets with clone 81 cells carrying a murine sarcoma genome but free of leukemia virus (S+L-). FeLV caused cell transformation that was easily visible 3-12 days after infection. This method is simple, sensitive, and easily read; it has the advantage of directly detecting infectious FeLV rather than viral antigens."}
{"id": "PMID:189038", "title": "A carcinogenicity assay of Mirex in Charles River CD rats.", "content": "The long-term administration of 50 and 100 ppm of Mirex in the diets of male and female Charles River CD rats was associated with a spectrum of liver lesions, from foci or areas of cellular alteration and neoplastic nodules to hepatocellular carcinoma. Statistically significant numbers of neoplastic nodules were observed in the livers of male rats receiving the high dose. Neoplastic nodules and hepatocellular carcinomas were not observed in control rats.", "contents": "A carcinogenicity assay of Mirex in Charles River CD rats. The long-term administration of 50 and 100 ppm of Mirex in the diets of male and female Charles River CD rats was associated with a spectrum of liver lesions, from foci or areas of cellular alteration and neoplastic nodules to hepatocellular carcinoma. Statistically significant numbers of neoplastic nodules were observed in the livers of male rats receiving the high dose. Neoplastic nodules and hepatocellular carcinomas were not observed in control rats."}
{"id": "PMID:189039", "title": "Possible carcinogenic effects of cedar shavings in bedding of C3H-Avy fB mice.", "content": "C3H-AvyfB female mice were tested on bedding consisting only of low-resin pine and on bedding of pine plus cedar shavings. Tumor occurrences were similar in both groups of animals, with a slightly lower incidence and slightly higher average age for mammary gland tumors in the females on bedding of pine plus cedar. From these results, the high incidence of cancer in the C3H-AvyfB strain could not be attributed to the routine use of cedar shavings in the bedding material.", "contents": "Possible carcinogenic effects of cedar shavings in bedding of C3H-Avy fB mice. C3H-AvyfB female mice were tested on bedding consisting only of low-resin pine and on bedding of pine plus cedar shavings. Tumor occurrences were similar in both groups of animals, with a slightly lower incidence and slightly higher average age for mammary gland tumors in the females on bedding of pine plus cedar. From these results, the high incidence of cancer in the C3H-AvyfB strain could not be attributed to the routine use of cedar shavings in the bedding material."}
{"id": "PMID:189040", "title": "Detection of complement-dependent lytic antibodies in sera from feline leukemia virus-infected cats by the chromium-51 release assay.", "content": "Sera from feline leukemia virus-infected cats lysed FL74 cells in the presence of an appropriate complement source; lysis was detected with the use of the 51 Cr release method. Serum complement from both rabbits and guinea pigs mediated lysis. Partial correlation of results was obtained from preliminary comparisons of lysis and immunofluorescence tests with the use of FL74 cells as targets.", "contents": "Detection of complement-dependent lytic antibodies in sera from feline leukemia virus-infected cats by the chromium-51 release assay. Sera from feline leukemia virus-infected cats lysed FL74 cells in the presence of an appropriate complement source; lysis was detected with the use of the 51 Cr release method. Serum complement from both rabbits and guinea pigs mediated lysis. Partial correlation of results was obtained from preliminary comparisons of lysis and immunofluorescence tests with the use of FL74 cells as targets."}
{"id": "PMID:189041", "title": "Transplantable murine salivary gland carcinoma (myoepithelioma). I. Biologic behavior and ultrastructural features.", "content": "Three salivary gland adenocarcinomas that arose spontaneously in female BALB/c mice, originally being maintained for plasmacytoma (MOPC) investigations, were studied; only one of the original hosts was MOPC-bearing. The initial carcinomas clearly originated from the salivary gland, not the breast, and did not resemble plasma cell lesions. The submandibular gland was the site of origin in each instance. Lesions were identical to those described previously in strains A and C mice as myoepitheliomas, with intracellular fibrils positive by phosphotungstic acid-hematoxylin (PTAH) stain. Each cell line (A, B, and C) of the salivary gland carcinomas was serially transplanted for 28, 29 and 14 generations, respecitvely. The lesion was easily transplanted, achieved almost 100% takes, and uniformly killed the host in 6-12 weeks, with metastasis to the peritoneum and liver. A myeloproliferative reaction characterized by leukemoid changes regularly occurred during the growth of the tumors. Each transplant generation was identical to its original salivary gland precursor by light and electron microscopy. In their growth pattern, the tumors resembled sarcomas with large areas of spindle cells. Ultrastructurally, the neoplastic cells contained the organelles of acinar and possibly ductal cells and exhibited varying degrees of synthetic and secretory activity, characterized by abundant free ribosomes and granular ergastoplasm, with prominent canaliculi containing abundant secretory material. Numerous desmosomes were seen, as well as coarse filaments and fine fibrils in most tumors cells, particularly in cells exhibiting lesser degrees of secretion. The filaments most likely represented the PTAH-positive intracellular fibrils observed by light microscopy. All tumors had numerous cells with resting features.", "contents": "Transplantable murine salivary gland carcinoma (myoepithelioma). I. Biologic behavior and ultrastructural features. Three salivary gland adenocarcinomas that arose spontaneously in female BALB/c mice, originally being maintained for plasmacytoma (MOPC) investigations, were studied; only one of the original hosts was MOPC-bearing. The initial carcinomas clearly originated from the salivary gland, not the breast, and did not resemble plasma cell lesions. The submandibular gland was the site of origin in each instance. Lesions were identical to those described previously in strains A and C mice as myoepitheliomas, with intracellular fibrils positive by phosphotungstic acid-hematoxylin (PTAH) stain. Each cell line (A, B, and C) of the salivary gland carcinomas was serially transplanted for 28, 29 and 14 generations, respecitvely. The lesion was easily transplanted, achieved almost 100% takes, and uniformly killed the host in 6-12 weeks, with metastasis to the peritoneum and liver. A myeloproliferative reaction characterized by leukemoid changes regularly occurred during the growth of the tumors. Each transplant generation was identical to its original salivary gland precursor by light and electron microscopy. In their growth pattern, the tumors resembled sarcomas with large areas of spindle cells. Ultrastructurally, the neoplastic cells contained the organelles of acinar and possibly ductal cells and exhibited varying degrees of synthetic and secretory activity, characterized by abundant free ribosomes and granular ergastoplasm, with prominent canaliculi containing abundant secretory material. Numerous desmosomes were seen, as well as coarse filaments and fine fibrils in most tumors cells, particularly in cells exhibiting lesser degrees of secretion. The filaments most likely represented the PTAH-positive intracellular fibrils observed by light microscopy. All tumors had numerous cells with resting features."}
{"id": "PMID:189042", "title": "Vesicular stomatitis virus-infected L1210 murine leukemia cells: increased immunogenicity and altered surface antigens.", "content": "Homogenates of L1210 cells infected in vitro with vesicular stomatitis virus (VSV) were immunogenic agains a tumor graft of 100 times the LD50 dose of L1210 cells\" whereas those of uninfected cells were not. The immunogenicity of intact X-irradiated L1210 cells was distinguishable from that of VSV-infected cell homogenates on the basis of the susceptibility of immunogenicity to experimental procedures used in preparation of the immunogenic homogenates: Homogenization of intact X-irradiated cells or their infection with VSV prior to irradiation led to loss of immunogenicity. In addition, uninfected cell homogenates were not made immunogenic nor was the immunogenicity of VSV-infected cell homogenates eliminated by X-irradiation. At the time of tumor challenge, sera from mice that were effectively immunized with VSV-infected cell homogenate showed a high VSV-neutralizing titer but no complement-dependent cytotoxicity for L1210 cells. Quantitative absorption studies demonstrated that VSV infection led to a marked reduction in L1210 surface antigens recognized by cytotoxic alloantibody; spatial association between these antigens and VSV antigens was not demonstrable on VSV-infected cells. Antigens recognized by heterologous antiserum to L1210 cells were also reduced following VSV infection.", "contents": "Vesicular stomatitis virus-infected L1210 murine leukemia cells: increased immunogenicity and altered surface antigens. Homogenates of L1210 cells infected in vitro with vesicular stomatitis virus (VSV) were immunogenic agains a tumor graft of 100 times the LD50 dose of L1210 cells\" whereas those of uninfected cells were not. The immunogenicity of intact X-irradiated L1210 cells was distinguishable from that of VSV-infected cell homogenates on the basis of the susceptibility of immunogenicity to experimental procedures used in preparation of the immunogenic homogenates: Homogenization of intact X-irradiated cells or their infection with VSV prior to irradiation led to loss of immunogenicity. In addition, uninfected cell homogenates were not made immunogenic nor was the immunogenicity of VSV-infected cell homogenates eliminated by X-irradiation. At the time of tumor challenge, sera from mice that were effectively immunized with VSV-infected cell homogenate showed a high VSV-neutralizing titer but no complement-dependent cytotoxicity for L1210 cells. Quantitative absorption studies demonstrated that VSV infection led to a marked reduction in L1210 surface antigens recognized by cytotoxic alloantibody; spatial association between these antigens and VSV antigens was not demonstrable on VSV-infected cells. Antigens recognized by heterologous antiserum to L1210 cells were also reduced following VSV infection."}
{"id": "PMID:189043", "title": "Incidence patterns of spontaneous tumors in BN/Bi rats.", "content": "The occurrence of tumors in 236 female and 74 male BN/Bi rats that were allowed to live out their normal lifespans was described. For most neoplasms, the risk of a rat dying with a specific tumor increased with age. Some tumors, however, had a peak incidence; therefore, animals surviving these periods were at less risk than were their younger cohorts. The number dying with metastatic cancers was greatest in females over 30 months of age. Unexpectedly, males had a peak risk period at 25-30 months, so that males that died in older age groups had less risk of dying with a metastatic tumor. Lesions were often multiple, even in rats dying at a young age. Surprisingly, the percent dead with multiple tumors did not increase significantly with age. Some animals in every age group died without a tumor, and the percentage without neoplasms did not decrease, even in the older age groups.", "contents": "Incidence patterns of spontaneous tumors in BN/Bi rats. The occurrence of tumors in 236 female and 74 male BN/Bi rats that were allowed to live out their normal lifespans was described. For most neoplasms, the risk of a rat dying with a specific tumor increased with age. Some tumors, however, had a peak incidence; therefore, animals surviving these periods were at less risk than were their younger cohorts. The number dying with metastatic cancers was greatest in females over 30 months of age. Unexpectedly, males had a peak risk period at 25-30 months, so that males that died in older age groups had less risk of dying with a metastatic tumor. Lesions were often multiple, even in rats dying at a young age. Surprisingly, the percent dead with multiple tumors did not increase significantly with age. Some animals in every age group died without a tumor, and the percentage without neoplasms did not decrease, even in the older age groups."}
{"id": "PMID:189045", "title": "Transient virus expression during murine leukemia induction by X-irradiation.", "content": "Most X-irradiation-induced thymomas in C57BL/6 mice are virus-free when assayed by immunofluorescence for the gs antigen (gsa) of murine leukemia virus (MuLV). Virus was induced transiently in bone marrow cells and later appeared in thymus cells. Six to 7 weeks post irradiation, thymocytes and bone marrow cells were MuLV gsa-negative and remained negative for the lifetime of most animals, whether or not they contracted overt leukemia. During the period when MuLV gsa-positive bone marrow cells were found, XC-positive syncytia-producing bone marrow cells were also found. Virus information was expressed, therefore, for a limited duration, long before any signs of leukemia in the animals were evident. MuLV gsa-positive  thymocytes taken from mice 4 weeks after X-irradiation were cocultivated with a series of indicator cells. B-tropic virus, in addition to a xenotropic virus, was isolated from these cells. Ecotropic virus was not found in normal mouse thymocytes, in irradiated thymocytes a few days after termination of the X-irradiation sequence, or in most primary thymomas. All thymocytes produced only xenotropic virus in the cocultivation assays. Expression of the ecotropic virus was, therefore, transient, as assayed by immunofluorescence, XC syncytia formation, and virus isolation from MuLV gsa-positive thymus cells.", "contents": "Transient virus expression during murine leukemia induction by X-irradiation. Most X-irradiation-induced thymomas in C57BL/6 mice are virus-free when assayed by immunofluorescence for the gs antigen (gsa) of murine leukemia virus (MuLV). Virus was induced transiently in bone marrow cells and later appeared in thymus cells. Six to 7 weeks post irradiation, thymocytes and bone marrow cells were MuLV gsa-negative and remained negative for the lifetime of most animals, whether or not they contracted overt leukemia. During the period when MuLV gsa-positive bone marrow cells were found, XC-positive syncytia-producing bone marrow cells were also found. Virus information was expressed, therefore, for a limited duration, long before any signs of leukemia in the animals were evident. MuLV gsa-positive  thymocytes taken from mice 4 weeks after X-irradiation were cocultivated with a series of indicator cells. B-tropic virus, in addition to a xenotropic virus, was isolated from these cells. Ecotropic virus was not found in normal mouse thymocytes, in irradiated thymocytes a few days after termination of the X-irradiation sequence, or in most primary thymomas. All thymocytes produced only xenotropic virus in the cocultivation assays. Expression of the ecotropic virus was, therefore, transient, as assayed by immunofluorescence, XC syncytia formation, and virus isolation from MuLV gsa-positive thymus cells."}
{"id": "PMID:189046", "title": "Inhibition of dimethylnitrosamine-induced strand breaks in liver DNA and liver cell necrosis by diethyldithiocarbamate.", "content": "Diethyldithiocarbamate (DEDTC) prevented dimethylnitrosamine (DMN)-induced strand breaks in liver DNA and liver cell necrosis in male Wistar rats. In contrast, DEDTC did not inhibit the fragmentation of liver DNA caused by several other chemical carcinogens (N-hydroxy-2-acetylaminofluorene, 3-hydroxyxanthine, aflatoxin B1, N-acetoxy-2-acetylaminofluorene, methyl methanesulfonate, methylnitrosourea, and methylazoxy-methanol acetate), whether or not they required metabolic activation. Aminoacetonitrile exerted an action similar to that of DEDTC. The inhibitory effect was transitory, lasting at least for 4 hours, and protection for longer than 4 hours required multiple administrations of DEDTC. DEDTC also inhibited the serum clearance of DMN, methylation of liver DNA, and oxidative demethylation of DMN in the in vitro hepatic microsomal system prepared from either male Wistar rats or from hamsters. Interference of the metabolism of DMN appeared to be the mechanism by which DEDTC arrested DMN-induced biochemical and biologic effects.", "contents": "Inhibition of dimethylnitrosamine-induced strand breaks in liver DNA and liver cell necrosis by diethyldithiocarbamate. Diethyldithiocarbamate (DEDTC) prevented dimethylnitrosamine (DMN)-induced strand breaks in liver DNA and liver cell necrosis in male Wistar rats. In contrast, DEDTC did not inhibit the fragmentation of liver DNA caused by several other chemical carcinogens (N-hydroxy-2-acetylaminofluorene, 3-hydroxyxanthine, aflatoxin B1, N-acetoxy-2-acetylaminofluorene, methyl methanesulfonate, methylnitrosourea, and methylazoxy-methanol acetate), whether or not they required metabolic activation. Aminoacetonitrile exerted an action similar to that of DEDTC. The inhibitory effect was transitory, lasting at least for 4 hours, and protection for longer than 4 hours required multiple administrations of DEDTC. DEDTC also inhibited the serum clearance of DMN, methylation of liver DNA, and oxidative demethylation of DMN in the in vitro hepatic microsomal system prepared from either male Wistar rats or from hamsters. Interference of the metabolism of DMN appeared to be the mechanism by which DEDTC arrested DMN-induced biochemical and biologic effects."}
{"id": "PMID:189047", "title": "Separation of cells containing R-type virus-like particles from a simian virus 40-induced hamster tumor cell line.", "content": "Cells derived from a simian virus 40-induced hamster fibrosarcoma were separated into two distinct cell bands of differing buoyant densities. The lighter cell band or fraction (F1) had a buoyant density range of 1.025-1.032 g/ml and comprised 3.8% of the total cells applied to the gradient, whereas the heavier cell fraction (F2) had a buoyant density range of 1.054-1.074 g/ml and comprised 95.3% of the total cells applied. Both cell fractions were tumorigenic and did not differ greatly in cell type, viability, mitotic index, or their ability to incorporate [3H]thymidine. However, ultrastructurally, the F1 cells contained R-type virus-like particles within dilated intracisternal spaces and exhibited cytoplasmic vacuoles. In the F2 cells, few detectable R-type particles and cytoplasmic vacuoles were revealed by electron microscopy. The F2 cells demonstrated a twofold greater ability to incorporate [14C]protein hydrolysate into proteins than did the F1 cells.", "contents": "Separation of cells containing R-type virus-like particles from a simian virus 40-induced hamster tumor cell line. Cells derived from a simian virus 40-induced hamster fibrosarcoma were separated into two distinct cell bands of differing buoyant densities. The lighter cell band or fraction (F1) had a buoyant density range of 1.025-1.032 g/ml and comprised 3.8% of the total cells applied to the gradient, whereas the heavier cell fraction (F2) had a buoyant density range of 1.054-1.074 g/ml and comprised 95.3% of the total cells applied. Both cell fractions were tumorigenic and did not differ greatly in cell type, viability, mitotic index, or their ability to incorporate [3H]thymidine. However, ultrastructurally, the F1 cells contained R-type virus-like particles within dilated intracisternal spaces and exhibited cytoplasmic vacuoles. In the F2 cells, few detectable R-type particles and cytoplasmic vacuoles were revealed by electron microscopy. The F2 cells demonstrated a twofold greater ability to incorporate [14C]protein hydrolysate into proteins than did the F1 cells."}
{"id": "PMID:189048", "title": "A continuous line of Rous sarcoma virus-transformed chick embryo cells.", "content": "A continuous line of Rous sarcoma virus (RSV)-transformed chick embryo cells was established. The cells, designated RTAZ-1, which constitute the only known line of continuously growing RSV-transformed cells of chick embryo origin, grow rapidly, display uniform morphology, and perpetually release large amounts of RSV (Rous-associated virus, type 1). RTAZ-1 cells display a heteroploid chromosome complement with 92-94 chromosomes characteristic of chicken cells. Molecular hybridization studies demonstrated that DNA from these cells hybridized with normal chick DNA but not with human (KB) cell DNA, thus providing additional evidence of the chicken origin of RTAZ-1.", "contents": "A continuous line of Rous sarcoma virus-transformed chick embryo cells. A continuous line of Rous sarcoma virus (RSV)-transformed chick embryo cells was established. The cells, designated RTAZ-1, which constitute the only known line of continuously growing RSV-transformed cells of chick embryo origin, grow rapidly, display uniform morphology, and perpetually release large amounts of RSV (Rous-associated virus, type 1). RTAZ-1 cells display a heteroploid chromosome complement with 92-94 chromosomes characteristic of chicken cells. Molecular hybridization studies demonstrated that DNA from these cells hybridized with normal chick DNA but not with human (KB) cell DNA, thus providing additional evidence of the chicken origin of RTAZ-1."}
{"id": "PMID:189049", "title": "Inhibition of hepatocarcinogenesis by adrenocorticotropin in aflatoxin B1-treated rats.", "content": "We examined whether hormones would modify the carcinogenic action of aflatoxin B1 (AFB1). Four groups of inbred Fischer rats received AFB1, 125 mug per animal, weekly per os. In three of the groups, certain hormones were administered simultaneously: One group received 1 U growth hormone (GH) sc weekly, another was given 4 U adrenocorticotropin (ACTH) weekly, and a third received 0.5 U insulin weekly sc. AFB1, ACTH, and insulin were given for 20 weeks; GH was given for only 10 weeks. The control group did not receive hormone adjuvant. In each group, 4 animals were killed at 7, 14, 21, 28, and 35 weeks; the remaining rats were killed at 77 weeks. Their livers were carefully examined and samples prepared for light and electron microscopy. Animals receiving AFB1 and ACTH failed to exhibit hepatocellular carcinoma. On the other hand, malignant lymphoma appeared at 56 weeks in 3 of the 6 surviving males on this regime. AFB1, alone or when given with insulin or GH, caused hepatocellular carcinoma in all animals; in these, lymphoma was not observed. Lymphoma comprised two cell types, each with similar neclear characteristics but differing in their nucleocytoplasmic ratios and in the amount and distribution of cytoplasmic organelles. Alterations leading to hepatocellular carcinoma were examined at various stages of development. \"Basophilic hyperplasia\" reflected an increase in free ribosomes. \"Hyperplastic nodules\" were composed of hepatocyte aggregates with characteristics similar to those encountered in the earlier stage. Both the \"neoplastic nodules\" and hepatocellular carcinomas were formed by cells containing large, \"smooth fingerprints\" and free ribosomal aggregates. These features supported the concept that AFB1 impairs ribosomal binding to endoplasmic reticulum membranes. The failure of ACTH-treated animals to develop hepatocellular carcinoma was ascribed to the effect of adrenal cortical stimulation upon membrane-polysome binding.", "contents": "Inhibition of hepatocarcinogenesis by adrenocorticotropin in aflatoxin B1-treated rats. We examined whether hormones would modify the carcinogenic action of aflatoxin B1 (AFB1). Four groups of inbred Fischer rats received AFB1, 125 mug per animal, weekly per os. In three of the groups, certain hormones were administered simultaneously: One group received 1 U growth hormone (GH) sc weekly, another was given 4 U adrenocorticotropin (ACTH) weekly, and a third received 0.5 U insulin weekly sc. AFB1, ACTH, and insulin were given for 20 weeks; GH was given for only 10 weeks. The control group did not receive hormone adjuvant. In each group, 4 animals were killed at 7, 14, 21, 28, and 35 weeks; the remaining rats were killed at 77 weeks. Their livers were carefully examined and samples prepared for light and electron microscopy. Animals receiving AFB1 and ACTH failed to exhibit hepatocellular carcinoma. On the other hand, malignant lymphoma appeared at 56 weeks in 3 of the 6 surviving males on this regime. AFB1, alone or when given with insulin or GH, caused hepatocellular carcinoma in all animals; in these, lymphoma was not observed. Lymphoma comprised two cell types, each with similar neclear characteristics but differing in their nucleocytoplasmic ratios and in the amount and distribution of cytoplasmic organelles. Alterations leading to hepatocellular carcinoma were examined at various stages of development. \"Basophilic hyperplasia\" reflected an increase in free ribosomes. \"Hyperplastic nodules\" were composed of hepatocyte aggregates with characteristics similar to those encountered in the earlier stage. Both the \"neoplastic nodules\" and hepatocellular carcinomas were formed by cells containing large, \"smooth fingerprints\" and free ribosomal aggregates. These features supported the concept that AFB1 impairs ribosomal binding to endoplasmic reticulum membranes. The failure of ACTH-treated animals to develop hepatocellular carcinoma was ascribed to the effect of adrenal cortical stimulation upon membrane-polysome binding."}
{"id": "PMID:189050", "title": "Chromosome banding patterns of two transplantable pituitary tumors induced in rats by 2,4,6-trimethylaniline.", "content": "The chromosomal constitution of a mammosomatotrophic and an inactive transplantable pituitary tumor induced in rats by 2,4,6-trimethylaniline was studied by the Giemsa-banding techniques. The inactive tumor line 7315i evolved from the active tumor line 7315a in one of the early transfers. A comparison was also made with chromosomal patterns of a transplantable rat hepatoma (7316A) induced by the same chemical carcinogen. Pituitary tumor line 7315a had a pseudotriploid complement with 63 chromosomes, whereas the inactive line 7315i was hypodiploid, with a dominant stemline of 36 chromosomes. The stemline chromosome number of the hepatoma was in the hypotetraploid region. Giemsa banding revealed that all chromosomes of the normal rat complement were present in both pituitary tumors. Four abnormal chromosomes were detected in the active tumor line and three in the inactive line. Both tumor lines contained a single minute chromosome. One common marker, a deleted chromosome No.1, was found in both pituitary tumors. This common marker chromosome was, however, not present in the hepatoma. The stemline karyotype of the hepatoma contained seven different markers, but none of them was identical to the abnormal chromosomes of the pituitary neoplasms. The findings suggested that the abnormal karyotypes of lines 7315a and 7315i could reflect the multisecretory activities of these neoplastic pituitary cells but that chromosomal localization of the secretory defect awaits exact genetic mapping of the rat chromosomes.", "contents": "Chromosome banding patterns of two transplantable pituitary tumors induced in rats by 2,4,6-trimethylaniline. The chromosomal constitution of a mammosomatotrophic and an inactive transplantable pituitary tumor induced in rats by 2,4,6-trimethylaniline was studied by the Giemsa-banding techniques. The inactive tumor line 7315i evolved from the active tumor line 7315a in one of the early transfers. A comparison was also made with chromosomal patterns of a transplantable rat hepatoma (7316A) induced by the same chemical carcinogen. Pituitary tumor line 7315a had a pseudotriploid complement with 63 chromosomes, whereas the inactive line 7315i was hypodiploid, with a dominant stemline of 36 chromosomes. The stemline chromosome number of the hepatoma was in the hypotetraploid region. Giemsa banding revealed that all chromosomes of the normal rat complement were present in both pituitary tumors. Four abnormal chromosomes were detected in the active tumor line and three in the inactive line. Both tumor lines contained a single minute chromosome. One common marker, a deleted chromosome No.1, was found in both pituitary tumors. This common marker chromosome was, however, not present in the hepatoma. The stemline karyotype of the hepatoma contained seven different markers, but none of them was identical to the abnormal chromosomes of the pituitary neoplasms. The findings suggested that the abnormal karyotypes of lines 7315a and 7315i could reflect the multisecretory activities of these neoplastic pituitary cells but that chromosomal localization of the secretory defect awaits exact genetic mapping of the rat chromosomes."}
{"id": "PMID:189051", "title": "Induction of malignant vascular tumors of the liver in guinea pigs treated with 2,2'-dihydroxy-di-n-propylnitrosamine.", "content": "The effect of chronic administration of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) was studied in randombred guinea pigs. DHPN, dissolved in olive oil, was injected sc into 40 animals at a dose of 250 mg/kg body weight/week for 30 weeks, and the animals were observed until their death or termination of the experiment at the end of 40 weeks. Of the 32 guinea pigs that survived more than 20 weeks of DHPN treatment, 23 developed angiosarcoma of the liver between 22 and 40 weeks. Metastases to lungs, spleen, and peripancreatic lymph nodes were observed in 8 animals. Other tumors included hepatocellular carcinoma (1 animal), cholangiocarcinoma (1 animal), chronic myeloid leukemia (1 animal), acinar cell adenoma of pancreas (1 animal), and acinar cell carcinoma of pancreas (1 animal). In addition, megalocytic change of hepatic cells with intranuclear inclusions, pelliosis hepatis, and cholangiomatous lesions were also encountered frequently in the livers.", "contents": "Induction of malignant vascular tumors of the liver in guinea pigs treated with 2,2'-dihydroxy-di-n-propylnitrosamine. The effect of chronic administration of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) was studied in randombred guinea pigs. DHPN, dissolved in olive oil, was injected sc into 40 animals at a dose of 250 mg/kg body weight/week for 30 weeks, and the animals were observed until their death or termination of the experiment at the end of 40 weeks. Of the 32 guinea pigs that survived more than 20 weeks of DHPN treatment, 23 developed angiosarcoma of the liver between 22 and 40 weeks. Metastases to lungs, spleen, and peripancreatic lymph nodes were observed in 8 animals. Other tumors included hepatocellular carcinoma (1 animal), cholangiocarcinoma (1 animal), chronic myeloid leukemia (1 animal), acinar cell adenoma of pancreas (1 animal), and acinar cell carcinoma of pancreas (1 animal). In addition, megalocytic change of hepatic cells with intranuclear inclusions, pelliosis hepatis, and cholangiomatous lesions were also encountered frequently in the livers."}
{"id": "PMID:189052", "title": "Horizontal transmission of feline leukemia virus under experimental conditions.", "content": "Thirty-seven specific-pathogen-free (SPF) cats ranging from newborn to 1 year were inoculated with the Rickard strain of feline leukemia virus (FeLV). Each inoculated cat shared a cage with a control SPF cat for 40 weeks post inoculation. After 4-5 weeks, 20 of the inoculated cats became group-specific antigen (gsa)-positive; the other 17 remained gsa-negative but developed virus neutralizing and feline oncornavirus cell membrane-associated antigen antibody titers. Seventeen of the control cats in contact with the gsa-positive cats developed evidence of FeLV infection 4-18 weeks after virema was detected in their inoculated cage mates. Of the control cats in contact with inoculated cats that remained gsa-negative, none developed evidence of FeLV infection. Data indicated that the gsa-positive state in cats inoculated with FeLV correlated with the capacity for horizontal transmission of the virus.", "contents": "Horizontal transmission of feline leukemia virus under experimental conditions. Thirty-seven specific-pathogen-free (SPF) cats ranging from newborn to 1 year were inoculated with the Rickard strain of feline leukemia virus (FeLV). Each inoculated cat shared a cage with a control SPF cat for 40 weeks post inoculation. After 4-5 weeks, 20 of the inoculated cats became group-specific antigen (gsa)-positive; the other 17 remained gsa-negative but developed virus neutralizing and feline oncornavirus cell membrane-associated antigen antibody titers. Seventeen of the control cats in contact with the gsa-positive cats developed evidence of FeLV infection 4-18 weeks after virema was detected in their inoculated cage mates. Of the control cats in contact with inoculated cats that remained gsa-negative, none developed evidence of FeLV infection. Data indicated that the gsa-positive state in cats inoculated with FeLV correlated with the capacity for horizontal transmission of the virus."}
{"id": "PMID:189053", "title": "Frog lysozyme. IV. Isozyme of lysozyme and the Luck\u00e9 renal adenocarcinoma.", "content": "The normal kidney of the frog Rana pipiens contains eight isozymes of lysozyme. Three of these, however, were not present in five Lucke renal adenocarcinomas. No isozymes were found to be unique to the tumor kidneys. Of the five isozymes detected in tumor kidneys, only one was uniformly present, a second was present in four of five tumors, and the appearance of the other three was highly variable, although no tumor kidney contained all of them. The uniform absence of the three isozymes and the variable distribution of the other five among the tumors attested to the metabolic uniqueness of this tumor and was consistent with a prior hypothesis concerning the role of lysozyme in the etiology of this herpesvirus-induced tumor.", "contents": "Frog lysozyme. IV. Isozyme of lysozyme and the Luck\u00e9 renal adenocarcinoma. The normal kidney of the frog Rana pipiens contains eight isozymes of lysozyme. Three of these, however, were not present in five Lucke renal adenocarcinomas. No isozymes were found to be unique to the tumor kidneys. Of the five isozymes detected in tumor kidneys, only one was uniformly present, a second was present in four of five tumors, and the appearance of the other three was highly variable, although no tumor kidney contained all of them. The uniform absence of the three isozymes and the variable distribution of the other five among the tumors attested to the metabolic uniqueness of this tumor and was consistent with a prior hypothesis concerning the role of lysozyme in the etiology of this herpesvirus-induced tumor."}
{"id": "PMID:189054", "title": "Herd health status of animals exposed to polybrominated biphenyls (PBB).", "content": "The health status of 16 herds of dairly cattle exposed to low levels of polybrominated bipenyl (PBB) was compared with that of 15 control herds. Milk production of the contaminated herds was not significantly changed in 1972, 1973, and 1974 and was not significantly different from that of control herds in the same years. Mortality of adult cows and calves, the percentages of cows culled from the herds because of old age and low production, disease, or sterility, and the general health conditions were similar in the two groups. Serum concentrations of calcium, glucose, and cholesterol in contaminated herds were significantly different from those of the control herds, but the relationship to PBB exposure needs further investigation.", "contents": "Herd health status of animals exposed to polybrominated biphenyls (PBB). The health status of 16 herds of dairly cattle exposed to low levels of polybrominated bipenyl (PBB) was compared with that of 15 control herds. Milk production of the contaminated herds was not significantly changed in 1972, 1973, and 1974 and was not significantly different from that of control herds in the same years. Mortality of adult cows and calves, the percentages of cows culled from the herds because of old age and low production, disease, or sterility, and the general health conditions were similar in the two groups. Serum concentrations of calcium, glucose, and cholesterol in contaminated herds were significantly different from those of the control herds, but the relationship to PBB exposure needs further investigation."}
{"id": "PMID:189055", "title": "Biological responsiveness to cholinesterase inhibition: a test for exploring the developmental maturity of the cholinergic system.", "content": "The acute mortality caused by two irreversible inhibitors of cholinesterases [diisopropylfluorophosphate (DFP) and diethoxyphosphorylthiocholine, 217 MI-phospholine iodide] has been investigated on chick embryos at different stages of development. The results demonstrate that the above compounds do not show any acute lethal action when administered before the 9th day of incubation; on the other hand, the administration is regularly followed by death after the 9th day of incubation. The doses are comparable to those causing death in hatched chicks. It has also been observed that no appreciable difference exists in DFP uptake from the yolk before and after the 9th day of incubation and that drug-induced cholinesterase inhibition is of the same order of magnitude at any developmental stage; the compound pyridine-2-aldoxime methanesulfonate (2-PAM) was a good antidote against DFP acute lethality. It seems likely that between the 8th and the 9th day of incubation the target system of organophosphorus inhibitors, that is, the cholinesterase enzymatic system, reaches a new point of maturation.", "contents": "Biological responsiveness to cholinesterase inhibition: a test for exploring the developmental maturity of the cholinergic system. The acute mortality caused by two irreversible inhibitors of cholinesterases [diisopropylfluorophosphate (DFP) and diethoxyphosphorylthiocholine, 217 MI-phospholine iodide] has been investigated on chick embryos at different stages of development. The results demonstrate that the above compounds do not show any acute lethal action when administered before the 9th day of incubation; on the other hand, the administration is regularly followed by death after the 9th day of incubation. The doses are comparable to those causing death in hatched chicks. It has also been observed that no appreciable difference exists in DFP uptake from the yolk before and after the 9th day of incubation and that drug-induced cholinesterase inhibition is of the same order of magnitude at any developmental stage; the compound pyridine-2-aldoxime methanesulfonate (2-PAM) was a good antidote against DFP acute lethality. It seems likely that between the 8th and the 9th day of incubation the target system of organophosphorus inhibitors, that is, the cholinesterase enzymatic system, reaches a new point of maturation."}
{"id": "PMID:189056", "title": "Effects of neonatal hypothyroidism on cerebral and cerebellar synaptosome development.", "content": "The effect of hypothyroidism on cerebral and cerebellar synaptosome development has been studied. Neonatal hypothyroidism was induced following addition of 0.3% propylthiouracil to the diet of nursing mothers. Maturation profiles of total synaptosome fraction and specific activities of lactate dehydrogenase, Na+K ATPase, cytochrome c oxidase, and protein were obtained from days 6 to 32 on synaptosomes isolated from Ficoll-sucrose gradients. The greatest changes were found in the total activities of enzymes isolated from the cerebellum. Hypothyroidism induced a retardation of LDH and cytochrome c oxidase in cerebellar synaptosomes, but no change in corresponding specific activities. Maximum rates of 14C-leucine incorporation into cerebellar synaptosome protein was found at 16-20 days, after which a rapid decline occurred to adult levels at 32 days. In neonatal hypothyroidism, synthesis was significantly reduced at 8 and 14 days, but reached control levels or above at 21--32 days. In the cerebrum, maximum rates of 14C-leucine incorporation into synaptosome protein were identified at 8--12 days in normal with a rapid drop to adult levels at approximately 20 days. In neonatal hypothyroidism, peak activities were identified at 14 days and increased activities over control were noted at 14, 20 and 30 days. These observations demonstrate the sensitivity of the developing cerebellar synaptic apparatus to neonatal hypothyroidism, with a protraction in the peak levels of synaptosome protein synthesis in cerebrum and cerebellum.", "contents": "Effects of neonatal hypothyroidism on cerebral and cerebellar synaptosome development. The effect of hypothyroidism on cerebral and cerebellar synaptosome development has been studied. Neonatal hypothyroidism was induced following addition of 0.3% propylthiouracil to the diet of nursing mothers. Maturation profiles of total synaptosome fraction and specific activities of lactate dehydrogenase, Na+K ATPase, cytochrome c oxidase, and protein were obtained from days 6 to 32 on synaptosomes isolated from Ficoll-sucrose gradients. The greatest changes were found in the total activities of enzymes isolated from the cerebellum. Hypothyroidism induced a retardation of LDH and cytochrome c oxidase in cerebellar synaptosomes, but no change in corresponding specific activities. Maximum rates of 14C-leucine incorporation into cerebellar synaptosome protein was found at 16-20 days, after which a rapid decline occurred to adult levels at 32 days. In neonatal hypothyroidism, synthesis was significantly reduced at 8 and 14 days, but reached control levels or above at 21--32 days. In the cerebrum, maximum rates of 14C-leucine incorporation into synaptosome protein were identified at 8--12 days in normal with a rapid drop to adult levels at approximately 20 days. In neonatal hypothyroidism, peak activities were identified at 14 days and increased activities over control were noted at 14, 20 and 30 days. These observations demonstrate the sensitivity of the developing cerebellar synaptic apparatus to neonatal hypothyroidism, with a protraction in the peak levels of synaptosome protein synthesis in cerebrum and cerebellum."}
{"id": "PMID:189058", "title": "Drug and immuno-diagnostic resistant amoebic liver abscess in Ibadan: an elucidation of a possible mechanism.", "content": "A thick fibrous walling of amoebic abscess of the liver is very rare. Using as a basis the case of drug and immunodiagnostic resistant amoebic liver abscess in an adult Nigerian, an account is given of the possible mechanisms for such therapeutic and diagnostic failure. A theory of blood-abscess cavity barrier is postulated and suggested as a mechanism for the constant failure to detect antibodies to E. histolytica in the small percentage of cases of amoebic liver abscess (Morris, Powell and Elsdon-Dew, 1970). A study of the rate of diffusion of amoebic excretion/secretion through a thick fibrous tissue or artificial membrane of comparable properties is strongly advocated.", "contents": "Drug and immuno-diagnostic resistant amoebic liver abscess in Ibadan: an elucidation of a possible mechanism. A thick fibrous walling of amoebic abscess of the liver is very rare. Using as a basis the case of drug and immunodiagnostic resistant amoebic liver abscess in an adult Nigerian, an account is given of the possible mechanisms for such therapeutic and diagnostic failure. A theory of blood-abscess cavity barrier is postulated and suggested as a mechanism for the constant failure to detect antibodies to E. histolytica in the small percentage of cases of amoebic liver abscess (Morris, Powell and Elsdon-Dew, 1970). A study of the rate of diffusion of amoebic excretion/secretion through a thick fibrous tissue or artificial membrane of comparable properties is strongly advocated."}
{"id": "PMID:189059", "title": "Endobronchial adenomata in children.", "content": "Two cases of carcinoid adenomata of the bronchus in children are added to 25 previously reported cases of bronchial adenomata in children in the literature. Carcinoid tumors represent close to 50 per cent of bronchial adenomata in children, with cylindromas (adenoid cystic) forming 13 per cent and mucoepidermoids two per cent. Over 1/3 of bronchial adenomata have metastases at the time of diagnosis. No cases of carcinoid syndrome have been reported in children. The treatment of choice is lobectomy with sleeve resection or, failing that, pulmonary resection. The overall five-year survival time varies from 50 to 80 per cent and is enhanced by surgical resection.", "contents": "Endobronchial adenomata in children. Two cases of carcinoid adenomata of the bronchus in children are added to 25 previously reported cases of bronchial adenomata in children in the literature. Carcinoid tumors represent close to 50 per cent of bronchial adenomata in children, with cylindromas (adenoid cystic) forming 13 per cent and mucoepidermoids two per cent. Over 1/3 of bronchial adenomata have metastases at the time of diagnosis. No cases of carcinoid syndrome have been reported in children. The treatment of choice is lobectomy with sleeve resection or, failing that, pulmonary resection. The overall five-year survival time varies from 50 to 80 per cent and is enhanced by surgical resection."}
{"id": "PMID:189060", "title": "Spontaneous mutations affecting the host range of the B77 strain of avian sarcoma virus involve type-specific changes in the virion envelope antigen.", "content": "Previously it was shown that the host-range gene of the Bratislava strain of avain sarcoma virus (B77 virus) spontaneously mutates with a very high rate. The wild-type B77 virus called B77 virus-II, mutates either to virus that efficiently infects duck cells (B77 virus-III) or to virus that does not mutate to the ability to infect duck cells (B77 virus-I) (Zarling and Temin, 1976). No significant differences in either the virion envelope glycoproteins or other major virion proteins were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, pseudotypes of B77 virus-I with proteins of a transformation-defective mutant of B77 virus-III formed foci efficiently in duck cells. An alteration in the envelope protein of B77 virus-I was demonstrated by experiments in which B77 firus-I was fused into duck cells with UV-irradiated Sendai virus and formed foci. Neutralization experiments further demonstrated that B77 virus host-range mutants have altered type-specific envelope antigens. Thus, the spontaneous mutations in the host-range gene of B77 virus involve changes in the type-specific virion envelope antigen.", "contents": "Spontaneous mutations affecting the host range of the B77 strain of avian sarcoma virus involve type-specific changes in the virion envelope antigen. Previously it was shown that the host-range gene of the Bratislava strain of avain sarcoma virus (B77 virus) spontaneously mutates with a very high rate. The wild-type B77 virus called B77 virus-II, mutates either to virus that efficiently infects duck cells (B77 virus-III) or to virus that does not mutate to the ability to infect duck cells (B77 virus-I) (Zarling and Temin, 1976). No significant differences in either the virion envelope glycoproteins or other major virion proteins were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, pseudotypes of B77 virus-I with proteins of a transformation-defective mutant of B77 virus-III formed foci efficiently in duck cells. An alteration in the envelope protein of B77 virus-I was demonstrated by experiments in which B77 firus-I was fused into duck cells with UV-irradiated Sendai virus and formed foci. Neutralization experiments further demonstrated that B77 virus host-range mutants have altered type-specific envelope antigens. Thus, the spontaneous mutations in the host-range gene of B77 virus involve changes in the type-specific virion envelope antigen."}
{"id": "PMID:189061", "title": "Steroid induction of mouse mammary tumor virus: effect upon synthesis and degradation of viral RNA.", "content": "Steroid hormones have been demonstrated to induce in tissue culture the production of mouse mammary tumor viral (MMTV) RNA, proteins, and particles 10-fold compared with constitutive levels. However, previous data of increased viral RNA levels did not distinguish between an increased rate of viral-specific RNA synthesis and a slower rate of viral RNA degradation. According to the recently developed assay of Coffin et al. (1974) for measuring rates of viral RNA synthesis, short-term labeling experiments of a mouse mammary tumor cell line indicate that the glucocorticoid hormone dexamethasone stimulates a 3-fold increase in the synthesis of MMTV-specific RNA within 10 min after the addition of hormone and that stimulation of RNA synthesis reaches 5- to 10-fold within 30 to 60 min, while the synthesis of Moloney leukemia virus-specific RNA in the same cell is unaffected by steroids. The decay rates of pulse-labeled and accumulated MMTV RNA in the presence or absence of dexamethasone show this RNA to have a half-life of greater than 8 h. In addition, hormone-stimulated MMTV RNA appears to have an increased rate of decay compared to basal MMTV RNA, thus ruling out an increased stability of MMTV RNA in the presence of steroid hormones as the basis for increased RNA levels. Thus, the magnitude, rapidity, and specificity of hormone action on MMTV RNA synthesis indicate a primary effect upon transcription.", "contents": "Steroid induction of mouse mammary tumor virus: effect upon synthesis and degradation of viral RNA. Steroid hormones have been demonstrated to induce in tissue culture the production of mouse mammary tumor viral (MMTV) RNA, proteins, and particles 10-fold compared with constitutive levels. However, previous data of increased viral RNA levels did not distinguish between an increased rate of viral-specific RNA synthesis and a slower rate of viral RNA degradation. According to the recently developed assay of Coffin et al. (1974) for measuring rates of viral RNA synthesis, short-term labeling experiments of a mouse mammary tumor cell line indicate that the glucocorticoid hormone dexamethasone stimulates a 3-fold increase in the synthesis of MMTV-specific RNA within 10 min after the addition of hormone and that stimulation of RNA synthesis reaches 5- to 10-fold within 30 to 60 min, while the synthesis of Moloney leukemia virus-specific RNA in the same cell is unaffected by steroids. The decay rates of pulse-labeled and accumulated MMTV RNA in the presence or absence of dexamethasone show this RNA to have a half-life of greater than 8 h. In addition, hormone-stimulated MMTV RNA appears to have an increased rate of decay compared to basal MMTV RNA, thus ruling out an increased stability of MMTV RNA in the presence of steroid hormones as the basis for increased RNA levels. Thus, the magnitude, rapidity, and specificity of hormone action on MMTV RNA synthesis indicate a primary effect upon transcription."}
{"id": "PMID:189062", "title": "Rate of divergence of cellular sequences homologous to segments of Moloney sarcoma virus.", "content": "The RNA genome of the Moloney isolate of murine sarcoma virus (M-MSV) consists of two parts--a sarcoma-specific region with no homology to known leukemia viral RNAs, and a shared region present also in Moloney murine leukemia virus RNA. Complementary DNA was isolated which was specific for each part of the M-MSV genome. The DNA of a number of mammalian species was examined for the presence of nucleotide sequences homologous with the two M-MSV regions. Both sets of viral sequences had homologous nucleotide sequences present in normal mouse cellular DNA. MSV-specific sequences found in mouse cellular DNA closely matched those nucleotide sequences found in M-MSV as seen by comparisons of thermal denaturation profiles. In all normal mouse cells tested, the cellular set of M-MSV-specific nucleotide sequences was present in DNA as one to a few copies per cell. The rate of base substitution of M-MSV nucleotide sequences was compared with the rate of evolution of both unique sequences and the hemoglobin gene of various species. Conservation of MSV-specific nucleotide sequences among species was similar to that of mouse globin gene(s) and greater than that of average unique cellular sequences. In contrast, cellular nucleotide sequences that are homologous to the M-MSV-murine leukemia virus \"common\" nucleotide region were present in multiple copies in mouse cells and were less well matched, as seen by reduced melting profiles of the hybrids. The cellular common nucleotide sequences diverged very rapidly during evolution, with a base substitution rate similar to that reported for some primate and avian endogenous virogenes. The observation that two sets of covalently linked viral sequences evolved at very different rates suggests that the origin of M-MSV may be different from endogenous helper viruses and that cellular sequences homologous to MSV-specific nucleotide sequences may be important to survival.", "contents": "Rate of divergence of cellular sequences homologous to segments of Moloney sarcoma virus. The RNA genome of the Moloney isolate of murine sarcoma virus (M-MSV) consists of two parts--a sarcoma-specific region with no homology to known leukemia viral RNAs, and a shared region present also in Moloney murine leukemia virus RNA. Complementary DNA was isolated which was specific for each part of the M-MSV genome. The DNA of a number of mammalian species was examined for the presence of nucleotide sequences homologous with the two M-MSV regions. Both sets of viral sequences had homologous nucleotide sequences present in normal mouse cellular DNA. MSV-specific sequences found in mouse cellular DNA closely matched those nucleotide sequences found in M-MSV as seen by comparisons of thermal denaturation profiles. In all normal mouse cells tested, the cellular set of M-MSV-specific nucleotide sequences was present in DNA as one to a few copies per cell. The rate of base substitution of M-MSV nucleotide sequences was compared with the rate of evolution of both unique sequences and the hemoglobin gene of various species. Conservation of MSV-specific nucleotide sequences among species was similar to that of mouse globin gene(s) and greater than that of average unique cellular sequences. In contrast, cellular nucleotide sequences that are homologous to the M-MSV-murine leukemia virus \"common\" nucleotide region were present in multiple copies in mouse cells and were less well matched, as seen by reduced melting profiles of the hybrids. The cellular common nucleotide sequences diverged very rapidly during evolution, with a base substitution rate similar to that reported for some primate and avian endogenous virogenes. The observation that two sets of covalently linked viral sequences evolved at very different rates suggests that the origin of M-MSV may be different from endogenous helper viruses and that cellular sequences homologous to MSV-specific nucleotide sequences may be important to survival."}
{"id": "PMID:189063", "title": "Photodynamic treatment of herpes simplex virus during its replicative cycle.", "content": "Photodynamic treatment of herpes simplex virus type 1-infected hamster embryo fibroblasts (LSH strain) with a low concentration of proflavine (0.08 mug/10(5) cells per ml), a 3-9-diamine acridine dye, inhibited production not only of infectious progeny but also of virion particles. However, there was no appreciable inhibition of viral or cellular DNA synthesis, even when the infected cells were repeatedly exposed to this low concentration of dye and light during the replication cycle of the virus. It thus appears that photodynamic treatment of infected cells interferes with the processes involved in virus maturation.", "contents": "Photodynamic treatment of herpes simplex virus during its replicative cycle. Photodynamic treatment of herpes simplex virus type 1-infected hamster embryo fibroblasts (LSH strain) with a low concentration of proflavine (0.08 mug/10(5) cells per ml), a 3-9-diamine acridine dye, inhibited production not only of infectious progeny but also of virion particles. However, there was no appreciable inhibition of viral or cellular DNA synthesis, even when the infected cells were repeatedly exposed to this low concentration of dye and light during the replication cycle of the virus. It thus appears that photodynamic treatment of infected cells interferes with the processes involved in virus maturation."}
{"id": "PMID:189064", "title": "Effects of temperature and antibody on the cyclid growth of vesicular stomatitis virus.", "content": "To see the effects of temperature on the interrelated cyclic production of standard and defective interfering (DI) particles of vesicular stomatitis virus, a temperature-sensitive (ts) G114 mutant was passaged successively at different temperatures and the production of the two types of viral particles as well as the ability of Chinese hamster ovary cells to survive each passage was continuously monitored. When the temperature was nonpermissive for standard virus, the synthesis of both standard and defective interfering particles was inhibited. When revertants appeared in the population, their ability to take over the infection depended on the permissiveness of the temperature for the temperature-sensitive mutant. At permissive temperatures periodic inhibition of both types of standard viruses was maintained by the production of defective interfering particles. Reverents did not become a majority of the population due to this periodic inhibition. When the conditions were nonpermissive for the mutant, revertants became the major standard virus in the population within a few passages. These findings can be understood if conditions of high and low multiplicities are dissected out together with a thorough understanding of the individual properties of each of the viral particles and of the result of interactions between them. In the presence of antiserum which neutralized only 90% of the viral particles, cyclic production of standard virus occurred, with a decline in the total amount of virus produced after each cycle. Therefore, in the presence of limiting concentrations of antiserum, the virus appeared to be able to establish a persistent cyclic growth pattern.", "contents": "Effects of temperature and antibody on the cyclid growth of vesicular stomatitis virus. To see the effects of temperature on the interrelated cyclic production of standard and defective interfering (DI) particles of vesicular stomatitis virus, a temperature-sensitive (ts) G114 mutant was passaged successively at different temperatures and the production of the two types of viral particles as well as the ability of Chinese hamster ovary cells to survive each passage was continuously monitored. When the temperature was nonpermissive for standard virus, the synthesis of both standard and defective interfering particles was inhibited. When revertants appeared in the population, their ability to take over the infection depended on the permissiveness of the temperature for the temperature-sensitive mutant. At permissive temperatures periodic inhibition of both types of standard viruses was maintained by the production of defective interfering particles. Reverents did not become a majority of the population due to this periodic inhibition. When the conditions were nonpermissive for the mutant, revertants became the major standard virus in the population within a few passages. These findings can be understood if conditions of high and low multiplicities are dissected out together with a thorough understanding of the individual properties of each of the viral particles and of the result of interactions between them. In the presence of antiserum which neutralized only 90% of the viral particles, cyclic production of standard virus occurred, with a decline in the total amount of virus produced after each cycle. Therefore, in the presence of limiting concentrations of antiserum, the virus appeared to be able to establish a persistent cyclic growth pattern."}
{"id": "PMID:189065", "title": "Cell-free synthesis of polyoma virus capsid proteins VP1 and VP2.", "content": "Polyadenylated RNA isolated from the cytoplasm of mouse 3T6 cells 28 h after infection with polyoma virus has been isolated and translated in vitro. Polyoma capsid proteins VP1 and VP2 have been identified in the cell-free product by polyacrylamide gel electrophoresis, specific immunoprecipitation, and tryptic peptide fingerprinting. Polyoma mRNA species have been isolated by preparative hybridization to purified viral DNA immobilized on cellulose nitrate filters and shown to code for both VP1 and VP2. These experiments establish conditions for the isolation of late polyoma mRNA and the cell-free synthesis of polyoma capsid proteins and indicate that the active mRNA species are at least partially virus coded.", "contents": "Cell-free synthesis of polyoma virus capsid proteins VP1 and VP2. Polyadenylated RNA isolated from the cytoplasm of mouse 3T6 cells 28 h after infection with polyoma virus has been isolated and translated in vitro. Polyoma capsid proteins VP1 and VP2 have been identified in the cell-free product by polyacrylamide gel electrophoresis, specific immunoprecipitation, and tryptic peptide fingerprinting. Polyoma mRNA species have been isolated by preparative hybridization to purified viral DNA immobilized on cellulose nitrate filters and shown to code for both VP1 and VP2. These experiments establish conditions for the isolation of late polyoma mRNA and the cell-free synthesis of polyoma capsid proteins and indicate that the active mRNA species are at least partially virus coded."}
{"id": "PMID:189066", "title": "Transmembrane phospholipid motions induced by F glycoprotein in hemagglutinating virus of Japan.", "content": "Transfer of phospholipid from the envelope of hemagglutinating virus of Japan (HVJ) to erythrocyte (RBC) membrane and the virus-induced transfer of phospholipid between RBC membranes were studied using spin-labeled phosphatidylcholine (PC). The transfer of PC from membranes labeled densely with PC to unlabeled membranes was followed by the peak height increase in the electron spin resonance spectrum. The two kinds of transfer reactions took place very rapidly as reported previously. To obtain further details, the transfer reactions were studied with HVJ, HVJ inactivated by trypsin, HVJ harvested early, HVJ grown in fibroblast cells, the fibroblast HVJ activated by trypsin, influenza virus, and glutaraldehyde-treated RBCs. The results demonstrated that the viral F glycoprotein played a crucial role in the transmembrane phospholipid movements as well as in the fusion and hemolysis of RBCs. The transfer from HVJ to RBC's occurred partially through an exchange mechanism not accompanying the envelope fusion. This was shown by a decrease in the exchange broadening of the electron spin resonance spectrum of released spin-labeled HVJ (HVJ) and also by an increase in the ratio of PC to viral proteins incorporated into RBC membranes. HVJ modified RBC membrane so as to be able to exchange its phospholipids with those of inactive membranes such as fibroblast HVJ, influenza virus, glutaraldehyde-treated RBC'S, and phosphatidylcholine vesicles. HVJ affected the fluidity of RBC membranes markedly, the environments around PC being much fluidized. The virus-induced fusion was discussed based on close apposition of the membranes by HANA proteins and on the destabilization and fluidization of RBC membranes by F glycoproteins.", "contents": "Transmembrane phospholipid motions induced by F glycoprotein in hemagglutinating virus of Japan. Transfer of phospholipid from the envelope of hemagglutinating virus of Japan (HVJ) to erythrocyte (RBC) membrane and the virus-induced transfer of phospholipid between RBC membranes were studied using spin-labeled phosphatidylcholine (PC). The transfer of PC from membranes labeled densely with PC to unlabeled membranes was followed by the peak height increase in the electron spin resonance spectrum. The two kinds of transfer reactions took place very rapidly as reported previously. To obtain further details, the transfer reactions were studied with HVJ, HVJ inactivated by trypsin, HVJ harvested early, HVJ grown in fibroblast cells, the fibroblast HVJ activated by trypsin, influenza virus, and glutaraldehyde-treated RBCs. The results demonstrated that the viral F glycoprotein played a crucial role in the transmembrane phospholipid movements as well as in the fusion and hemolysis of RBCs. The transfer from HVJ to RBC's occurred partially through an exchange mechanism not accompanying the envelope fusion. This was shown by a decrease in the exchange broadening of the electron spin resonance spectrum of released spin-labeled HVJ (HVJ) and also by an increase in the ratio of PC to viral proteins incorporated into RBC membranes. HVJ modified RBC membrane so as to be able to exchange its phospholipids with those of inactive membranes such as fibroblast HVJ, influenza virus, glutaraldehyde-treated RBC'S, and phosphatidylcholine vesicles. HVJ affected the fluidity of RBC membranes markedly, the environments around PC being much fluidized. The virus-induced fusion was discussed based on close apposition of the membranes by HANA proteins and on the destabilization and fluidization of RBC membranes by F glycoproteins."}
{"id": "PMID:189067", "title": "Inhibition of host cell protein synthesis by UV-inactivated poliovirus.", "content": "The ability of poliovirus that was irradiated with UV light at energies up to 2,160 ergs/mm2 to subsequently inhibit host cell protein synthesis was measured. The inactivation of the host cell shutoff function followed one-hit kinetics. Increasing irradiation did not affect the rate of inhibition until the multiplicity of infection after irradiation was reduced to approximately 1 PFU/cell. At higher functional multiplicities, the rate was unchanged, but an increasing lag before the onset of inhibition was observed with increasing irradiation. The energy levels required to inactivate virus-induced inhibition of host cell protein synthesis suggest that damage to virus RNA rather than to virus capsid proteins is responsible for the loss of function. When the inactivation of host cell shutoff was compared with the inactivation of other viral functions by UV irradiation, it correlated exactly with the loss of infectivity but not with other viral functions measured. Guanidine treatment, which prevents detectable viral RNA and protein synthesis, completely inhibited host cell shutoff by low multiplicities of unirradiated virus infection but not higher multiplicities. When a high multiplicity of virus was first reduced to a low titer by irradiation, host cell shutoff was still evident in the presence of guanidine. The results demonstrate that the complete inhibition of host cell protein synthesis can be accomplished by one infectious viral genome per cell.", "contents": "Inhibition of host cell protein synthesis by UV-inactivated poliovirus. The ability of poliovirus that was irradiated with UV light at energies up to 2,160 ergs/mm2 to subsequently inhibit host cell protein synthesis was measured. The inactivation of the host cell shutoff function followed one-hit kinetics. Increasing irradiation did not affect the rate of inhibition until the multiplicity of infection after irradiation was reduced to approximately 1 PFU/cell. At higher functional multiplicities, the rate was unchanged, but an increasing lag before the onset of inhibition was observed with increasing irradiation. The energy levels required to inactivate virus-induced inhibition of host cell protein synthesis suggest that damage to virus RNA rather than to virus capsid proteins is responsible for the loss of function. When the inactivation of host cell shutoff was compared with the inactivation of other viral functions by UV irradiation, it correlated exactly with the loss of infectivity but not with other viral functions measured. Guanidine treatment, which prevents detectable viral RNA and protein synthesis, completely inhibited host cell shutoff by low multiplicities of unirradiated virus infection but not higher multiplicities. When a high multiplicity of virus was first reduced to a low titer by irradiation, host cell shutoff was still evident in the presence of guanidine. The results demonstrate that the complete inhibition of host cell protein synthesis can be accomplished by one infectious viral genome per cell."}
{"id": "PMID:189068", "title": "Anatomy of herpes simplex virus DNA VII. alpha-RNA is homologous to noncontiguous sites in both the L and S components of viral DNA.", "content": "Previous reports from this laboratory (Honess and Roizman, 1974) have operationally defined alpha polypeptides as the viral proteins that are synthesized first in HEp-2 cells treated with cycloheximide from the time of infection with herpes simplex virus type 1 until the withdrawal of the drug 12 to 15 h after infection. It has also been shown that the viral RNA (designated alpha RNA) that accumulates in the cytoplasm during cycloheximide treatment and on polyribosomes immediately upon withdrawal of the drug is homologous to 10 to 12% of viral DNA, whereas the viral RNA accumulating in the cytoplasm of untreated cells at 8 to 14 h after infection is homologous to 43% of viral DNA (Kozak and Roizman, 1974). In the present study, alpha RNA and cytoplasmic RNA extracted from untreated cells 8 h after infection were each hybridized in liquid to in vitro labeled restriction endonuclease fragments generated by cleavage of herpes simplex virus type 1 DNA with Hsu I, with Bgl II, and with both enzymes simultaneously. The data show that only a subset of the fragments hybridized to alpha RNA, and these are scattered within both the L and S components of the DNA. There are at least five noncontiguous regions in the DNA homologous to alpha RNA; two of these are located partially within the reiterated sequences in the S component. All fragments tested hybridized more extensively with 8-h cytoplasmic RNA than with alpha RNA. Four adjacent fragments, corresponding to 30% of the DNA and mapping within the L component, hybridized exclusively with the cytoplasmic RNA extracted from cells 8 h after infection.", "contents": "Anatomy of herpes simplex virus DNA VII. alpha-RNA is homologous to noncontiguous sites in both the L and S components of viral DNA. Previous reports from this laboratory (Honess and Roizman, 1974) have operationally defined alpha polypeptides as the viral proteins that are synthesized first in HEp-2 cells treated with cycloheximide from the time of infection with herpes simplex virus type 1 until the withdrawal of the drug 12 to 15 h after infection. It has also been shown that the viral RNA (designated alpha RNA) that accumulates in the cytoplasm during cycloheximide treatment and on polyribosomes immediately upon withdrawal of the drug is homologous to 10 to 12% of viral DNA, whereas the viral RNA accumulating in the cytoplasm of untreated cells at 8 to 14 h after infection is homologous to 43% of viral DNA (Kozak and Roizman, 1974). In the present study, alpha RNA and cytoplasmic RNA extracted from untreated cells 8 h after infection were each hybridized in liquid to in vitro labeled restriction endonuclease fragments generated by cleavage of herpes simplex virus type 1 DNA with Hsu I, with Bgl II, and with both enzymes simultaneously. The data show that only a subset of the fragments hybridized to alpha RNA, and these are scattered within both the L and S components of the DNA. There are at least five noncontiguous regions in the DNA homologous to alpha RNA; two of these are located partially within the reiterated sequences in the S component. All fragments tested hybridized more extensively with 8-h cytoplasmic RNA than with alpha RNA. Four adjacent fragments, corresponding to 30% of the DNA and mapping within the L component, hybridized exclusively with the cytoplasmic RNA extracted from cells 8 h after infection."}
{"id": "PMID:189069", "title": "Six-NB-tropic murine leukemia viruses derived from a B-tropic virus of BALB/c have altered p30.", "content": "We have examined the electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels of three virion proteins of B-tropic murine leukemia virus from BALB/c and six of its NB-tropic derivatives. The gp70 protein and a 13,000-molecular-weight virion protein tentatively identified as p15 of the NB-tropic viruses migrated with the corresponding B virus proteins. However, the major internal structural protein of type C virions, p30, of all the NB-tropic viruses migrated more rapidly than the p30 of their B virus progenitor. Although this change in p30 raises the possibility that p30 may be involved in determining the N-, B-, or NB-tropism of MuLV's, it is also possible that the change accompanies but does not directly determine the change in tropsim.", "contents": "Six-NB-tropic murine leukemia viruses derived from a B-tropic virus of BALB/c have altered p30. We have examined the electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels of three virion proteins of B-tropic murine leukemia virus from BALB/c and six of its NB-tropic derivatives. The gp70 protein and a 13,000-molecular-weight virion protein tentatively identified as p15 of the NB-tropic viruses migrated with the corresponding B virus proteins. However, the major internal structural protein of type C virions, p30, of all the NB-tropic viruses migrated more rapidly than the p30 of their B virus progenitor. Although this change in p30 raises the possibility that p30 may be involved in determining the N-, B-, or NB-tropism of MuLV's, it is also possible that the change accompanies but does not directly determine the change in tropsim."}
{"id": "PMID:189070", "title": "Application of freeze-drying intact cells to studies of murine oncornavirus morphogenesis.", "content": "Using a method for freeze-drying intact cells, uninfected and murine leukemia virus (MuLV)-infected JLSV9 cell surfaces, as well as murine mammary tumor virus (MuMTV)-infected cell surfaces, were examined by electron microscopy. The 10-nm knobs of MuLV and the 5-nm spikes of MuMTV were clearly revealed on the surfaces of budding viruses and were also found dispersed over the cell surface. The MuLV knobs are randomly arranged on the virus surface, whereas the MuMTV spikes are much more ordered. Because freeze-fractured budding viral envelopes are devoid of intramembranous particles, the observed surface particles do not appear to be merely accentuated intramembranous particles. This technique should permit further analysis of the morphogenesis of viral envelopes without the need for externally applied labels.", "contents": "Application of freeze-drying intact cells to studies of murine oncornavirus morphogenesis. Using a method for freeze-drying intact cells, uninfected and murine leukemia virus (MuLV)-infected JLSV9 cell surfaces, as well as murine mammary tumor virus (MuMTV)-infected cell surfaces, were examined by electron microscopy. The 10-nm knobs of MuLV and the 5-nm spikes of MuMTV were clearly revealed on the surfaces of budding viruses and were also found dispersed over the cell surface. The MuLV knobs are randomly arranged on the virus surface, whereas the MuMTV spikes are much more ordered. Because freeze-fractured budding viral envelopes are devoid of intramembranous particles, the observed surface particles do not appear to be merely accentuated intramembranous particles. This technique should permit further analysis of the morphogenesis of viral envelopes without the need for externally applied labels."}
{"id": "PMID:189071", "title": "Tunicamycin inhibits glycosylation and multiplication of Sindbis and vesicular stomatitis viruses.", "content": "Tunicamycin (TM), an antibiotic that inhibits the formation of N-acetylglucosamine-lipid intermediates, thereby preventing the glycosylation of newly synthesized glycoproteins, inhibits the growth of Sindbis virus and vesicular stomatitis virus in BHK cells. At 0.5 mug of TM per ml, the replication of both viruses is inhibited 99.9%. Noninfectious particles were not detected. All the viral proteins were synthesized in the presence of TM, but the glycoproteins were selectively altered in that they migrated faster than normal viral glycoproteins when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting defective glycosylation. Within 1 h after TM addition, [14C]glucosamine incorporation into glycoproteins was inhibited 20%, whereas [35S]methionine incorporation was unaffected. By 2 to 3 h after TM addition, glucosamine incorporation had fallen to 15% of control value, with methionine incorporation being 60% of normal. TM did not affect the growth of the nomenveloped encephalomyocarditis virus in BHK cells, demonstrating that TM is not a general inhibitor of protein synthesis. These data demonstrate that TM specifically inhibits the glycosylation of viral glycoproteins and that glycosylation may be essential for the normal assembly of enveloped viral particles.", "contents": "Tunicamycin inhibits glycosylation and multiplication of Sindbis and vesicular stomatitis viruses. Tunicamycin (TM), an antibiotic that inhibits the formation of N-acetylglucosamine-lipid intermediates, thereby preventing the glycosylation of newly synthesized glycoproteins, inhibits the growth of Sindbis virus and vesicular stomatitis virus in BHK cells. At 0.5 mug of TM per ml, the replication of both viruses is inhibited 99.9%. Noninfectious particles were not detected. All the viral proteins were synthesized in the presence of TM, but the glycoproteins were selectively altered in that they migrated faster than normal viral glycoproteins when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting defective glycosylation. Within 1 h after TM addition, [14C]glucosamine incorporation into glycoproteins was inhibited 20%, whereas [35S]methionine incorporation was unaffected. By 2 to 3 h after TM addition, glucosamine incorporation had fallen to 15% of control value, with methionine incorporation being 60% of normal. TM did not affect the growth of the nomenveloped encephalomyocarditis virus in BHK cells, demonstrating that TM is not a general inhibitor of protein synthesis. These data demonstrate that TM specifically inhibits the glycosylation of viral glycoproteins and that glycosylation may be essential for the normal assembly of enveloped viral particles."}
{"id": "PMID:189072", "title": "Complexity and polyadenylic acid content of visna virus 60-70S RNA.", "content": "The genomic complexity of visna virus was measured by quantitative analysis of 18 RNase T1-resistant oligonucleotides from 60-70S RNA. T1-resistant oligonucleotides were separated by two-dimensional polyacrylamide gel electrophoresis. Visna virus had a genomic complexity of 3.6 X 10(6) daltons, very close to the size of a single 30-40S RNA subunit. It was therefore concluded that the visna virus genome is largely polyploid. Visna virus 60-70S RNA polyadenylic acid segment was purified by T1 RNase digestion followed by oligodeoxythymidylic acid-cellulose column chromatography. It contained over 99% AMP and had a size of about 200 nucleotides. The binding capacities on oligodeoxythymidylic acid-cellulose of native 60-70S RNA and purified 30-40S RNA subunits were examined. It was concluded that two out of three intact subunits contain a polyadenylic acid segment.", "contents": "Complexity and polyadenylic acid content of visna virus 60-70S RNA. The genomic complexity of visna virus was measured by quantitative analysis of 18 RNase T1-resistant oligonucleotides from 60-70S RNA. T1-resistant oligonucleotides were separated by two-dimensional polyacrylamide gel electrophoresis. Visna virus had a genomic complexity of 3.6 X 10(6) daltons, very close to the size of a single 30-40S RNA subunit. It was therefore concluded that the visna virus genome is largely polyploid. Visna virus 60-70S RNA polyadenylic acid segment was purified by T1 RNase digestion followed by oligodeoxythymidylic acid-cellulose column chromatography. It contained over 99% AMP and had a size of about 200 nucleotides. The binding capacities on oligodeoxythymidylic acid-cellulose of native 60-70S RNA and purified 30-40S RNA subunits were examined. It was concluded that two out of three intact subunits contain a polyadenylic acid segment."}
{"id": "PMID:189073", "title": "Rifampin-susceptible mutant of vesicular stomatitis virus: protein and RNA synthesis.", "content": "A rifampin-susceptible strain (VSV Rif+) was selected from the wild vesicular stomatitis virus (VSV) population unsusceptible to rifampin. The VSV Rif+ was blocked in its intracellular replication in the presence of rifampin. In cells, rifampin affected primarily VSV Rif+ transcription, but to a different extent than in a cell-free system. In addition, a decrease in the amount of VSV Rif+ protein M was detected, linked to a stimulation of protein NS. In the absence of rifampin, protein M, although synthesized, was not immediately incorporated into the cell membrane. An interpretation of these observations is proposed.", "contents": "Rifampin-susceptible mutant of vesicular stomatitis virus: protein and RNA synthesis. A rifampin-susceptible strain (VSV Rif+) was selected from the wild vesicular stomatitis virus (VSV) population unsusceptible to rifampin. The VSV Rif+ was blocked in its intracellular replication in the presence of rifampin. In cells, rifampin affected primarily VSV Rif+ transcription, but to a different extent than in a cell-free system. In addition, a decrease in the amount of VSV Rif+ protein M was detected, linked to a stimulation of protein NS. In the absence of rifampin, protein M, although synthesized, was not immediately incorporated into the cell membrane. An interpretation of these observations is proposed."}
{"id": "PMID:189074", "title": "Transcriptional mapping of vesicular stomatitis virus in vivo.", "content": "Synthesis of the proteins of vesicular stomatitis virus (Indiana serotype) was studied in mouse L cells infected with virus that had been exposed to UV radiation. The UV target sizes measured during primary transcription indicated that the five genes occupy a single transcriptional unit. Thus, in infected cells, as a cell-free system, transcription of vesicular stomatitis virus RNA initiates at a single point and proceeds in the order N. NS, M, G, and L.", "contents": "Transcriptional mapping of vesicular stomatitis virus in vivo. Synthesis of the proteins of vesicular stomatitis virus (Indiana serotype) was studied in mouse L cells infected with virus that had been exposed to UV radiation. The UV target sizes measured during primary transcription indicated that the five genes occupy a single transcriptional unit. Thus, in infected cells, as a cell-free system, transcription of vesicular stomatitis virus RNA initiates at a single point and proceeds in the order N. NS, M, G, and L."}
{"id": "PMID:189075", "title": "Presence of deletion molecules in human wart virus DNA.", "content": "Deletion mutants of human wart virus were found to occur occasionally in the virus population transmitted in vivo, although the majority of virion DNA molecules were homogeneous in length and base sequence. Human wart virus DNA was 1.48 times as long as nondefective simian virus 40 DNA.", "contents": "Presence of deletion molecules in human wart virus DNA. Deletion mutants of human wart virus were found to occur occasionally in the virus population transmitted in vivo, although the majority of virion DNA molecules were homogeneous in length and base sequence. Human wart virus DNA was 1.48 times as long as nondefective simian virus 40 DNA."}
{"id": "PMID:189076", "title": "Influence of defective virion core proteins on RNA maturation with an avian sarcoma virus.", "content": "The RNA of the avian sarcoma virus B77 temperature-sensitive mutant LA334 was investigated using electrophoretic analysis. The RNA from mutant virus grown at the nonpermissive temperature (42degrees C) showed a heterogeneous peak between 80 and 125S, and another at about 35S. The RNA of the mutant virus grown at the permissive temperature (35 degrees C) behaved like wild-type B77 virus RNA, exhibiting a major peak at 70S. The homology between the various RNA fractions and virus-specific DNA probe was determined, indicating that mutant virus grown at the nonpermissive temperature contains relatively large amounts of nonviral-specific RNA.", "contents": "Influence of defective virion core proteins on RNA maturation with an avian sarcoma virus. The RNA of the avian sarcoma virus B77 temperature-sensitive mutant LA334 was investigated using electrophoretic analysis. The RNA from mutant virus grown at the nonpermissive temperature (42degrees C) showed a heterogeneous peak between 80 and 125S, and another at about 35S. The RNA of the mutant virus grown at the permissive temperature (35 degrees C) behaved like wild-type B77 virus RNA, exhibiting a major peak at 70S. The homology between the various RNA fractions and virus-specific DNA probe was determined, indicating that mutant virus grown at the nonpermissive temperature contains relatively large amounts of nonviral-specific RNA."}
{"id": "PMID:189077", "title": "Loss of supercoiled viral DNA after infection of permissive cells by simian virus 40.", "content": "During infection of BS-C-1 cells (a permissive line of monkey kidney cells) with simian virus 40, there was a loss of infecting viral supercoiled (component I) DNA molecules which was partially inhibited by cycloheximide. The kinetics of loss of component I in the presence of cycloheximide suggested that the loss was the result of at least two activities acting on the DNA, one cycloheximide sensitive and the second cycloheximide insensitive. Nucleotides from degraded infecting viral DNA were reincorporated into cell DNA that was synthesized during the infection.", "contents": "Loss of supercoiled viral DNA after infection of permissive cells by simian virus 40. During infection of BS-C-1 cells (a permissive line of monkey kidney cells) with simian virus 40, there was a loss of infecting viral supercoiled (component I) DNA molecules which was partially inhibited by cycloheximide. The kinetics of loss of component I in the presence of cycloheximide suggested that the loss was the result of at least two activities acting on the DNA, one cycloheximide sensitive and the second cycloheximide insensitive. Nucleotides from degraded infecting viral DNA were reincorporated into cell DNA that was synthesized during the infection."}
{"id": "PMID:189078", "title": "Use of defective interfering particle RNA probes in the determination of the order of in vitro transcription of vesicular stomatitis virus genes.", "content": "Annealing of various defective interfering particle RNAs of vesicular stomatitis virus to early in vitro viral transcription products has shown that transcription is sequential, with 13S to 18S mRNA's being produced first. Based on this finding, the 30S mRNA cistron is located at the 5' end of the viral genome.", "contents": "Use of defective interfering particle RNA probes in the determination of the order of in vitro transcription of vesicular stomatitis virus genes. Annealing of various defective interfering particle RNAs of vesicular stomatitis virus to early in vitro viral transcription products has shown that transcription is sequential, with 13S to 18S mRNA's being produced first. Based on this finding, the 30S mRNA cistron is located at the 5' end of the viral genome."}
{"id": "PMID:189079", "title": "Synthesis of Epstein-Barr virus DNA in vitro: effects of phosphonoacetic acid, N-ethylmaleimide, and ATP.", "content": "Nuclei from superinfected Raji cells synthesized Epstein-Barr Virus (EBV) DNA in vitro in the absence of cell DNA synthesis. The synthesis of EBV DNA in vitro was inhibited by phosphonoacetic acid and N-ethylmaleimide, and maximum synthesis was achieved in the absence of an ATP-regenerating system. Nuclei from mock-infected cells required an ATP-regenerating system for maximum DNA synthesis.", "contents": "Synthesis of Epstein-Barr virus DNA in vitro: effects of phosphonoacetic acid, N-ethylmaleimide, and ATP. Nuclei from superinfected Raji cells synthesized Epstein-Barr Virus (EBV) DNA in vitro in the absence of cell DNA synthesis. The synthesis of EBV DNA in vitro was inhibited by phosphonoacetic acid and N-ethylmaleimide, and maximum synthesis was achieved in the absence of an ATP-regenerating system. Nuclei from mock-infected cells required an ATP-regenerating system for maximum DNA synthesis."}
{"id": "PMID:189080", "title": "Possible in vitro repair of viral RNA by ligase-like enzyme(s) in poliovirus-infected cells.", "content": "A soluble polymerase-template complex prepared from poliovirus-infected cells was found to incorporate radioactive UTP into trichloroacetic acid-insoluble RNA linearly for 8 h in the presence of ATP and Mg2+. Radioactive CTP or GTP was not incorporated under identical conditions. Nearest-neighbor analysis of the in vitro product demonstrated that ATP was added to the viral RNA in the form of polyadenylic acid; UTP was added internally to the 3'-OH group of all four nucelotides. The data can best be explained by the addition of the UTP to the 3'-OH groups of single-stranded breaks in the double-stranded viral RNA and ligation to the adjacent 5'-phosphate groups. The enzymatic activity was also found in encephalomyocarditis virus- and rhinovirus type 1A-infected cells but not in uninfected cells.", "contents": "Possible in vitro repair of viral RNA by ligase-like enzyme(s) in poliovirus-infected cells. A soluble polymerase-template complex prepared from poliovirus-infected cells was found to incorporate radioactive UTP into trichloroacetic acid-insoluble RNA linearly for 8 h in the presence of ATP and Mg2+. Radioactive CTP or GTP was not incorporated under identical conditions. Nearest-neighbor analysis of the in vitro product demonstrated that ATP was added to the viral RNA in the form of polyadenylic acid; UTP was added internally to the 3'-OH group of all four nucelotides. The data can best be explained by the addition of the UTP to the 3'-OH groups of single-stranded breaks in the double-stranded viral RNA and ligation to the adjacent 5'-phosphate groups. The enzymatic activity was also found in encephalomyocarditis virus- and rhinovirus type 1A-infected cells but not in uninfected cells."}
{"id": "PMID:189081", "title": "Evidence for a diffusible T4 bacteriophage protein governing the initiation of delayed early RNA synthesis.", "content": "Two forms of prereplicative phage RNA can be discerned in Escherichia coli early after infection with bacteriophage T4, immediate early and delayed early RNA. The transition from immediate early to delayed early RNA synthesis is inhibited by chloramphenicol. The present work presents evidence for the existence of a phage-specific protein, which effects this transition. Delayed early RNA formation was measured by a cistron-specific enzyme-forming-capacity method, in which RNA synthesized in the presence of chloramphenicol was allowed to express itself into enzyme activity after (i) the addition of rifampin to inhibit further transcription and (ii) subsequent removal of chloramphenicol. As representatives of delayed early transcription, the two phage-specific enzymes dCTPase and deoxynucleotide kinase were chosen. Primary infection with a phage mutant defective in one of these two enzymes was found to induce a diffusible factor, which in the presence of chloramphenicol could effect the formation of delayed early RNA corresponding to the missing enzyme, upon superinfection with wild-type phage. The activity of this factor, acting in trans, was abolished by the amino acid analogue ethionine. Mutation in the suA gene of the host did not relieve phage of the apparent need for protein synthesis in the transition from immediate early to delayed early phage RNA synthesis.", "contents": "Evidence for a diffusible T4 bacteriophage protein governing the initiation of delayed early RNA synthesis. Two forms of prereplicative phage RNA can be discerned in Escherichia coli early after infection with bacteriophage T4, immediate early and delayed early RNA. The transition from immediate early to delayed early RNA synthesis is inhibited by chloramphenicol. The present work presents evidence for the existence of a phage-specific protein, which effects this transition. Delayed early RNA formation was measured by a cistron-specific enzyme-forming-capacity method, in which RNA synthesized in the presence of chloramphenicol was allowed to express itself into enzyme activity after (i) the addition of rifampin to inhibit further transcription and (ii) subsequent removal of chloramphenicol. As representatives of delayed early transcription, the two phage-specific enzymes dCTPase and deoxynucleotide kinase were chosen. Primary infection with a phage mutant defective in one of these two enzymes was found to induce a diffusible factor, which in the presence of chloramphenicol could effect the formation of delayed early RNA corresponding to the missing enzyme, upon superinfection with wild-type phage. The activity of this factor, acting in trans, was abolished by the amino acid analogue ethionine. Mutation in the suA gene of the host did not relieve phage of the apparent need for protein synthesis in the transition from immediate early to delayed early phage RNA synthesis."}
{"id": "PMID:189082", "title": "Assembly of viral membranes. I. Association of vesicular stomatitis virus membrane proteins and membranes in a cell-free system.", "content": "We report here an in vitro system designed to study the interactions of vesicular stomatitis virus (VSV) proteins with cellular membranes. We have synthesized the VSV nucleocapsid (N) protein, nonstructural (NS) protein, glycoprotein (G protein), and membrane (M) protein in a wheat germ, cell-free, protein-synthesizing system directed by VSV 12 to 18S RNA. When incubated at low salt concentrations with purified cytoplasmic membranes derived from Chinese hamster ovary cells, the VSV M andG proteins bind to membranes, whereas the VSV N and NS proteins do not. The VSV M protein binds to membranes in low or high divalent cation concentrations, whereas binding of significant amounts of G protein requires at least 5 mM magnesium acetate concentrations.", "contents": "Assembly of viral membranes. I. Association of vesicular stomatitis virus membrane proteins and membranes in a cell-free system. We report here an in vitro system designed to study the interactions of vesicular stomatitis virus (VSV) proteins with cellular membranes. We have synthesized the VSV nucleocapsid (N) protein, nonstructural (NS) protein, glycoprotein (G protein), and membrane (M) protein in a wheat germ, cell-free, protein-synthesizing system directed by VSV 12 to 18S RNA. When incubated at low salt concentrations with purified cytoplasmic membranes derived from Chinese hamster ovary cells, the VSV M andG proteins bind to membranes, whereas the VSV N and NS proteins do not. The VSV M protein binds to membranes in low or high divalent cation concentrations, whereas binding of significant amounts of G protein requires at least 5 mM magnesium acetate concentrations."}
{"id": "PMID:189083", "title": "Expression and thermal stability of simian virus 40 tumor-specific transplantation antigen and tumor antigen in wild type- and tsA mutant-transformed cells.", "content": "We have explored aspects of a suggested relationship between the expression of simian virus 40 tumor-specific transplantation antigen (TSTA) and tumor antigen (TA). A unique rat embryo cell line transformed by a temperature-sensitive A mutant that loses TA during exposure to the nonpermissive temperature (A28-RE) was found to lose TSTA. On the other hand, a typical control tsA-transformed cell line (A239-MB) expressed both TA and TSTA at the non-permissive temperature. TA in lysates obtained from A239-MB cells was found to be three to four times more thermolabile by covwt-mb) when incubated at either 33 or 40 degrees C. These data complement previous reports using TA from lytic infection and are consistent with the suggestion that TA is virus encoded. In contrast to TA, which even in wild-type-transformed cells was completely destroyed in less than 10 min at 50 degrees C, TSTA, assayed in vivo by tumor rejection, and tumor-specific surface antigen(s) TSSA) defined by an in vitro cytolytic assay, were thermostabile. Even after 24 h of incubation of extracts of 50 degrees C, high levels of TSTA and TSSA activity were present. Since these surface antigens when obtained from cells transformed by tsA mutants were also thermostabile, they could not be distinguished from the wild-type antigens. These results (i) indicate a coordinate expression of TA and TSTA in transformed cells; (ii) confirm that TA is virus encoded; and (iii) confirm that tha antigenic and immunogenic determinants that characterize TA and TSTA activities are distinct. However, the possibility that TSTA, like TA, is of viral rather than cellular origin is not excluded.", "contents": "Expression and thermal stability of simian virus 40 tumor-specific transplantation antigen and tumor antigen in wild type- and tsA mutant-transformed cells. We have explored aspects of a suggested relationship between the expression of simian virus 40 tumor-specific transplantation antigen (TSTA) and tumor antigen (TA). A unique rat embryo cell line transformed by a temperature-sensitive A mutant that loses TA during exposure to the nonpermissive temperature (A28-RE) was found to lose TSTA. On the other hand, a typical control tsA-transformed cell line (A239-MB) expressed both TA and TSTA at the non-permissive temperature. TA in lysates obtained from A239-MB cells was found to be three to four times more thermolabile by covwt-mb) when incubated at either 33 or 40 degrees C. These data complement previous reports using TA from lytic infection and are consistent with the suggestion that TA is virus encoded. In contrast to TA, which even in wild-type-transformed cells was completely destroyed in less than 10 min at 50 degrees C, TSTA, assayed in vivo by tumor rejection, and tumor-specific surface antigen(s) TSSA) defined by an in vitro cytolytic assay, were thermostabile. Even after 24 h of incubation of extracts of 50 degrees C, high levels of TSTA and TSSA activity were present. Since these surface antigens when obtained from cells transformed by tsA mutants were also thermostabile, they could not be distinguished from the wild-type antigens. These results (i) indicate a coordinate expression of TA and TSTA in transformed cells; (ii) confirm that TA is virus encoded; and (iii) confirm that tha antigenic and immunogenic determinants that characterize TA and TSTA activities are distinct. However, the possibility that TSTA, like TA, is of viral rather than cellular origin is not excluded."}
{"id": "PMID:189084", "title": "Purification of DNA complementary to the env gene of avian sarcoma virus and analysis of relationships among the env genes of avian leukosis-sarcoma viruses.", "content": "The env gene of avian leukosis-sarcoma viruses encodes a glycoprotein that determines the host range and surface antigenicitiy of virions. We have purified radioactive DNA (cDNAgp) complementary to at least a portion of the env gene for viral subgroups A and C; complementary DNA was synthesized with purified virions of wild-type avian sarcoma virus, and RNA from a mutant with a deletion in env was used to select DNA specific to env by molecular hybridization. The genetic complexity of cDNAgp for subgroup A (ca. 2,000 nucleotides) was sufficient to represent the entire deletion and most or all of the env cistron. The deletions in env in two independently isolated strains of virus (Bryan and rdNY8SR) overlap, and cDNAgp represents nucleotide sequences common to both deletions. By contrast, we could detect no overlap between deletions in env and deletions in the adjacent viral gene src. Laboratory stocks of viral subgroups A, B, C, D and E do not contain detectable amounts of env deletions when tested by molecular hybridization; hence, segregation of deletions in env is a less frequent event that the segregation of deletions in the viral transforming gene src (Vogt, 1971). We found extensive homology among the nucleotide sequences encoding the env genes of virus strains indigenous to chickens (subgroups A, B, C, D, and E) although subgorups B, D and E appear to differ slightly from subgroups A and C at the env locus. By contrast, viruses obtained from pheasant cells (subgroups F and G) have env genes with little or no relationship to env genes of chikcen viruses. According to available data, viruses of subgroup F arose by recombination between an avarian sarcoma virus and viral genes in the genome of ring-necked pheasants, whereas subgroup G viruses may be entirely endogenous to golden pheasants.", "contents": "Purification of DNA complementary to the env gene of avian sarcoma virus and analysis of relationships among the env genes of avian leukosis-sarcoma viruses. The env gene of avian leukosis-sarcoma viruses encodes a glycoprotein that determines the host range and surface antigenicitiy of virions. We have purified radioactive DNA (cDNAgp) complementary to at least a portion of the env gene for viral subgroups A and C; complementary DNA was synthesized with purified virions of wild-type avian sarcoma virus, and RNA from a mutant with a deletion in env was used to select DNA specific to env by molecular hybridization. The genetic complexity of cDNAgp for subgroup A (ca. 2,000 nucleotides) was sufficient to represent the entire deletion and most or all of the env cistron. The deletions in env in two independently isolated strains of virus (Bryan and rdNY8SR) overlap, and cDNAgp represents nucleotide sequences common to both deletions. By contrast, we could detect no overlap between deletions in env and deletions in the adjacent viral gene src. Laboratory stocks of viral subgroups A, B, C, D and E do not contain detectable amounts of env deletions when tested by molecular hybridization; hence, segregation of deletions in env is a less frequent event that the segregation of deletions in the viral transforming gene src (Vogt, 1971). We found extensive homology among the nucleotide sequences encoding the env genes of virus strains indigenous to chickens (subgroups A, B, C, D, and E) although subgorups B, D and E appear to differ slightly from subgroups A and C at the env locus. By contrast, viruses obtained from pheasant cells (subgroups F and G) have env genes with little or no relationship to env genes of chikcen viruses. According to available data, viruses of subgroup F arose by recombination between an avarian sarcoma virus and viral genes in the genome of ring-necked pheasants, whereas subgroup G viruses may be entirely endogenous to golden pheasants."}
{"id": "PMID:189085", "title": "Variations in integration site of avian oncornaviruses in different hosts.", "content": "We examined the integration site of avian oncornaviruses in the genome of different hosts with respect to the repetitive frequency of the cellular DNA sequences adjacent to the integrated proviral DNA. The following systems were studied: avian sarcoma virus (B-77) and avian leukosis virus (Rous-associated virus-61) in cultured duck embryonic cells and B-77 in cultured mouse 3T3 cells. These systems represent different host responses to viral infection, i.e., one in which both cellular transformation and viral replication occur (B-77-infected duck cells), one in which viral replication, but not transformation, occurs (Rous-associated virus-61-infected duck cells), and one in which transformation, but not viral replication, occurs (B-77-infected 3T3 cells). Two sequential hybridizations were used. First, large denatured DNA fragments (2.8 X 10(6) daltons) were reassociated to different C0t (mole-seconds per liter) values. Next, DNA remaining single stranded at different C0t values was isolated by hydroxylapatite column chromatography, immobilized on nitrocellulose filters, and hybridized with an excess of 3H-labeled 35S viral RNA to titrate the concentration of proviral DNA. Results show that B-77 sarcoma virus and Rous-associated virus-61 integrate in the unique region of duck DNA, whereas B-77 proviral DNA is associated with both repeated and unique host DNA sequences in transformed mouse 3T3 cells.", "contents": "Variations in integration site of avian oncornaviruses in different hosts. We examined the integration site of avian oncornaviruses in the genome of different hosts with respect to the repetitive frequency of the cellular DNA sequences adjacent to the integrated proviral DNA. The following systems were studied: avian sarcoma virus (B-77) and avian leukosis virus (Rous-associated virus-61) in cultured duck embryonic cells and B-77 in cultured mouse 3T3 cells. These systems represent different host responses to viral infection, i.e., one in which both cellular transformation and viral replication occur (B-77-infected duck cells), one in which viral replication, but not transformation, occurs (Rous-associated virus-61-infected duck cells), and one in which transformation, but not viral replication, occurs (B-77-infected 3T3 cells). Two sequential hybridizations were used. First, large denatured DNA fragments (2.8 X 10(6) daltons) were reassociated to different C0t (mole-seconds per liter) values. Next, DNA remaining single stranded at different C0t values was isolated by hydroxylapatite column chromatography, immobilized on nitrocellulose filters, and hybridized with an excess of 3H-labeled 35S viral RNA to titrate the concentration of proviral DNA. Results show that B-77 sarcoma virus and Rous-associated virus-61 integrate in the unique region of duck DNA, whereas B-77 proviral DNA is associated with both repeated and unique host DNA sequences in transformed mouse 3T3 cells."}
{"id": "PMID:189086", "title": "Picornaviral capsid assembly: similarity of rhinovirus and enterovirus precursor subunits.", "content": "Cytoplasmic extracts of rhinovirus 1A-infected HeLa cells, pulsed 15 min with [3H]leucine, contained a 13S subunit which was rich in the capsid precursor, peptide 92. After a 30-min chase, most of the capsid-related protein sedimented in a 14S peak that contained equimolar amounts of the capsid peptides epsilon, alpha, and gamma, and some residual chain 92. The 14S subunit could be dissociated at pH 4.8 into 6S subunits containing only epsilon, alpha, and gamma chains in equal proportions, indicating that the 14S subunit is an oligomer of (epsilon gamma alpha) protomers. These subunits resemble subunits previously identified in the assembly of enteroviruses. These observations support the idea that rhinovirus assembly is basically similar to that of enteroviruses. Comparative studies on the peptide stoichiometry of the virion and the capsid precursor subunits indicate that rhinovirus 1A can contain as many as 11 immature protomers per virion.", "contents": "Picornaviral capsid assembly: similarity of rhinovirus and enterovirus precursor subunits. Cytoplasmic extracts of rhinovirus 1A-infected HeLa cells, pulsed 15 min with [3H]leucine, contained a 13S subunit which was rich in the capsid precursor, peptide 92. After a 30-min chase, most of the capsid-related protein sedimented in a 14S peak that contained equimolar amounts of the capsid peptides epsilon, alpha, and gamma, and some residual chain 92. The 14S subunit could be dissociated at pH 4.8 into 6S subunits containing only epsilon, alpha, and gamma chains in equal proportions, indicating that the 14S subunit is an oligomer of (epsilon gamma alpha) protomers. These subunits resemble subunits previously identified in the assembly of enteroviruses. These observations support the idea that rhinovirus assembly is basically similar to that of enteroviruses. Comparative studies on the peptide stoichiometry of the virion and the capsid precursor subunits indicate that rhinovirus 1A can contain as many as 11 immature protomers per virion."}
{"id": "PMID:189087", "title": "Infectious linear DNA sequences replicating in simian virus 40-infected cells.", "content": "A new class of linear duplex DNA structures that contain simian virus 40 (SV40) DNA sequences and that are replicated during productive infection of cells with SV40 is described. These structures comprise up to 35% of the radioactively labeled DNA molecules that can be isolated by selective extraction. These molecules represent a unique size class corresponding to the length of an open SV40 DNA molecule (FO III), and they contain a heterogeneous population of DNA sequences either of host or of viral origin, as shown by restriction endonuclease analysis and nucleic acid hybridization. Part of the FO III DNA molecules contain viral-host DNA sequences covalently linked with each other. They start to replicate with the onset of SV40 superhelix replication 1 day after infection. Their rate of synthesis is most pronounced 3 days after infection when superhelix replication is already declining. Furthermore, they cannot be chased into other structures. At least a fraction of these molecules is infectious when administered together with DEAE-dextran to permissive cells. After intracellular circularization, superhelical DNA FO I with an aberrant cleavage pattern accumulates. In addition, tumor and viral capsid antigen are induced, and infectious viral progeny is obtained. Infection of cells with purified SV40 FO I DNA does not result in FO III DNA molecules in the infected cells or in the viral progeny. It is suggested, therefore, that these FO III DNA molecules are perpetuated within SV40 virus pools by encapsidation into pseudovirions.", "contents": "Infectious linear DNA sequences replicating in simian virus 40-infected cells. A new class of linear duplex DNA structures that contain simian virus 40 (SV40) DNA sequences and that are replicated during productive infection of cells with SV40 is described. These structures comprise up to 35% of the radioactively labeled DNA molecules that can be isolated by selective extraction. These molecules represent a unique size class corresponding to the length of an open SV40 DNA molecule (FO III), and they contain a heterogeneous population of DNA sequences either of host or of viral origin, as shown by restriction endonuclease analysis and nucleic acid hybridization. Part of the FO III DNA molecules contain viral-host DNA sequences covalently linked with each other. They start to replicate with the onset of SV40 superhelix replication 1 day after infection. Their rate of synthesis is most pronounced 3 days after infection when superhelix replication is already declining. Furthermore, they cannot be chased into other structures. At least a fraction of these molecules is infectious when administered together with DEAE-dextran to permissive cells. After intracellular circularization, superhelical DNA FO I with an aberrant cleavage pattern accumulates. In addition, tumor and viral capsid antigen are induced, and infectious viral progeny is obtained. Infection of cells with purified SV40 FO I DNA does not result in FO III DNA molecules in the infected cells or in the viral progeny. It is suggested, therefore, that these FO III DNA molecules are perpetuated within SV40 virus pools by encapsidation into pseudovirions."}
{"id": "PMID:189088", "title": "Junin virus structural proteins.", "content": "Polyacrylamide gel electrophoresis of purified Junin virus revealed six distinct structural polypeptides, two major and four minor ones. Four of these polypeptides appeared to be covalently linked with carbohydrate. The molecular weights of the six proteins, estimated by coelectrophoresis with marker proteins, ranged from 25,000 to 91,000. One of the two major components (number 3) was identified as a nucleoprotein and had a molecular weight of 64,000. It was the most prominent protein and was nonglycosylated. The other major protein (number 5), with a molecular weight of 38,000, was a glucoprotein and a component of the viral envelope. The location on the virion of three additional glycopeptides with molecular weights of 91,000, 72,000, and 52,000, together with a protein with a molecular weight of 25,000, was not well defined.", "contents": "Junin virus structural proteins. Polyacrylamide gel electrophoresis of purified Junin virus revealed six distinct structural polypeptides, two major and four minor ones. Four of these polypeptides appeared to be covalently linked with carbohydrate. The molecular weights of the six proteins, estimated by coelectrophoresis with marker proteins, ranged from 25,000 to 91,000. One of the two major components (number 3) was identified as a nucleoprotein and had a molecular weight of 64,000. It was the most prominent protein and was nonglycosylated. The other major protein (number 5), with a molecular weight of 38,000, was a glucoprotein and a component of the viral envelope. The location on the virion of three additional glycopeptides with molecular weights of 91,000, 72,000, and 52,000, together with a protein with a molecular weight of 25,000, was not well defined."}
{"id": "PMID:189089", "title": "Herpes simplex virus resistance and sensitivity to phosphonoacetic acid.", "content": "Phosphonoacetic acid (PAA) inhibited the synthesis of herpes simplex virus DNA in infected cells and the activity of the virus-specific DNA polymerase in vitro. In the presence of concentrations of PAA sufficient to prevent virus growth and virus DNA synthesis, normal amounts of early virus proteins (alpha- and beta-groups) were made, but late virus proteins (gamma-group) were reduced to less than 15% of amounts made in untreated infected cells. This residual PAA-insensitive synthesis of gamma-polypeptides occurred early in the virus growth cycle when rates were identical in PAA-treated and untreated infected cells. Passage of virus in the presence of PAA resulted in selection of mutants resistant to the drug. Stable clones of mutant viruses with a range of drug sensitivities were isolated and the emergence of variants resistant to high concentrations of PAA involved the sequential selection of mutants progressively better adapted to growth in the presence of the drug. Increased drug resistance of virus yield or plaque formation was correlated with increased resistance of virus DNA synthesis, gamma-protein synthesis, and resistance of the virus DNA polymerase reaction in vitro to the inhibitory effects of the drug. PAA-resistant strains of herpes simplex virus type 1 (HSV-1) complemented the growth of sensitive strains of homologous and heterologous types in mixed infections in the presence of the drug. Complementation was markedly dependent upon the proportions of the resistant and sensitive partners participating in the mixed infection. Intratypic (HSV-1A X HSV-1B) recombination of the PAA resistance marker(s), Pr, occurred at high frequency relative to plaque morphology (syn) and bromodeoxyuridine resistance (Br, thymidine kinase-negative phenotype) markers, with the most likely order being syn-Br-Pr. Recombinant viruses were as resistant or sensitive to PAA as the parental viruses, and viruses recombinant for their PAA resistance phenotype were also recombinant for the PAA resistance character of the virus DNA polymerase. The results provide additional evidence that the herpesvirus DNA polymerase is the site of action of PAA and illustrate the potential usefulness of PAA-resistant mutants in genetic studies of herpesviruses.", "contents": "Herpes simplex virus resistance and sensitivity to phosphonoacetic acid. Phosphonoacetic acid (PAA) inhibited the synthesis of herpes simplex virus DNA in infected cells and the activity of the virus-specific DNA polymerase in vitro. In the presence of concentrations of PAA sufficient to prevent virus growth and virus DNA synthesis, normal amounts of early virus proteins (alpha- and beta-groups) were made, but late virus proteins (gamma-group) were reduced to less than 15% of amounts made in untreated infected cells. This residual PAA-insensitive synthesis of gamma-polypeptides occurred early in the virus growth cycle when rates were identical in PAA-treated and untreated infected cells. Passage of virus in the presence of PAA resulted in selection of mutants resistant to the drug. Stable clones of mutant viruses with a range of drug sensitivities were isolated and the emergence of variants resistant to high concentrations of PAA involved the sequential selection of mutants progressively better adapted to growth in the presence of the drug. Increased drug resistance of virus yield or plaque formation was correlated with increased resistance of virus DNA synthesis, gamma-protein synthesis, and resistance of the virus DNA polymerase reaction in vitro to the inhibitory effects of the drug. PAA-resistant strains of herpes simplex virus type 1 (HSV-1) complemented the growth of sensitive strains of homologous and heterologous types in mixed infections in the presence of the drug. Complementation was markedly dependent upon the proportions of the resistant and sensitive partners participating in the mixed infection. Intratypic (HSV-1A X HSV-1B) recombination of the PAA resistance marker(s), Pr, occurred at high frequency relative to plaque morphology (syn) and bromodeoxyuridine resistance (Br, thymidine kinase-negative phenotype) markers, with the most likely order being syn-Br-Pr. Recombinant viruses were as resistant or sensitive to PAA as the parental viruses, and viruses recombinant for their PAA resistance phenotype were also recombinant for the PAA resistance character of the virus DNA polymerase. The results provide additional evidence that the herpesvirus DNA polymerase is the site of action of PAA and illustrate the potential usefulness of PAA-resistant mutants in genetic studies of herpesviruses."}
{"id": "PMID:189090", "title": "Morphogenesis of vesicular stomatitis virus: electron microscope observations with freeze-fracture techniques.", "content": "The morphogenesis of vesicular stomatitis virus was examined using freeze-fracture techniques, and the results obtained were compared with those from previously published experiments carried out with influenza viruses and togaviruses. The process of conversion of the host cell plasma membrane into the vesicular stomatitis virus envelope was accompanied by a loss of the intramembranal particles abundant in cell membranes. Frequently a dense accumulation of intramembranal particles could be seen at the base of the developing virion, suggesting that these structures might play some role in the generation of viral envelope. In addition to the viral structures that were seen to develop in the classical fashion, with their long axis perpendicular to the cell surface, structures were also found that suggested the initiation of a process similar to budding, with the long axis of the viral capsid parallel to the plasma membrane. In this situation, as in the \"perpendicular\" process, intramembranal particles were excluded from the viral structure, and an accumulation of these particles could be seen adjacent to the developing viral membrane.", "contents": "Morphogenesis of vesicular stomatitis virus: electron microscope observations with freeze-fracture techniques. The morphogenesis of vesicular stomatitis virus was examined using freeze-fracture techniques, and the results obtained were compared with those from previously published experiments carried out with influenza viruses and togaviruses. The process of conversion of the host cell plasma membrane into the vesicular stomatitis virus envelope was accompanied by a loss of the intramembranal particles abundant in cell membranes. Frequently a dense accumulation of intramembranal particles could be seen at the base of the developing virion, suggesting that these structures might play some role in the generation of viral envelope. In addition to the viral structures that were seen to develop in the classical fashion, with their long axis perpendicular to the cell surface, structures were also found that suggested the initiation of a process similar to budding, with the long axis of the viral capsid parallel to the plasma membrane. In this situation, as in the \"perpendicular\" process, intramembranal particles were excluded from the viral structure, and an accumulation of these particles could be seen adjacent to the developing viral membrane."}
{"id": "PMID:189091", "title": "Identification of simian virus 40 protein A.", "content": "A large simian virus 40 (SV40)-specific protein can be efficiently immunoprecipitated from infected cell extracts with antisera obtained from hamsters bearing SV40-induced tumors. The protein has an apparent molecular weight of 88,000 to 100,000 with respect to markers with known molecular weights, but behaves anomalously on sodium dodecyl sulfate (SDS)-polyacrylamide gels. Cell lines infected by two different strains of SV40 synthesize immunoreactive proteins that differ slightly in mobility during SDS-polyacrylamide gel electrophoresis, evidence that the protein is coded for by the virus. These differences in protein size correlate with differences in the electrophoretic mobility of viral DNA fragments obtained by digestion with HindII and III restriction enzymes. The size of the viral capsid proteins VP2 and VP3 also varies with the strain of virus. dl-1001, a constructed deletion mutant that lacks part of the SV40A gene, directs the synthesis of a 33,000-dalton polypeptide that is not detected in cells infected with wild-type virus. The deletion fragment, like the larger protein, is phosphorylated. Maps of tryptic peptides from the 88,000- to 100,000-dalton protein and the 33,000-dalton fragment show common peptides and provide strong direct evidence that the proteins are products of the SV40 A gene. The deletion fragment reacts with antitumor sera and binds to double-stranded DNA in the presence of the complete A protein.", "contents": "Identification of simian virus 40 protein A. A large simian virus 40 (SV40)-specific protein can be efficiently immunoprecipitated from infected cell extracts with antisera obtained from hamsters bearing SV40-induced tumors. The protein has an apparent molecular weight of 88,000 to 100,000 with respect to markers with known molecular weights, but behaves anomalously on sodium dodecyl sulfate (SDS)-polyacrylamide gels. Cell lines infected by two different strains of SV40 synthesize immunoreactive proteins that differ slightly in mobility during SDS-polyacrylamide gel electrophoresis, evidence that the protein is coded for by the virus. These differences in protein size correlate with differences in the electrophoretic mobility of viral DNA fragments obtained by digestion with HindII and III restriction enzymes. The size of the viral capsid proteins VP2 and VP3 also varies with the strain of virus. dl-1001, a constructed deletion mutant that lacks part of the SV40A gene, directs the synthesis of a 33,000-dalton polypeptide that is not detected in cells infected with wild-type virus. The deletion fragment, like the larger protein, is phosphorylated. Maps of tryptic peptides from the 88,000- to 100,000-dalton protein and the 33,000-dalton fragment show common peptides and provide strong direct evidence that the proteins are products of the SV40 A gene. The deletion fragment reacts with antitumor sera and binds to double-stranded DNA in the presence of the complete A protein."}
{"id": "PMID:189092", "title": "Modification of simian virus 40 protein A.", "content": "The A protein of simian virus 40 is phosphorylated in both productive and transforming infection. The phosphorylated amino acid has been identified as serine and has been localized in a single tryptic peptide of the protein. Because the A protein synthesized in infection by A mutants is phosphorylated to the same extent and in the same peptide as in infection by wild-type virus, the functional defect of the A mutants is apparently unrelated to phosphorylation. At least three distinct forms of the A protein with apparent molecular weights of 85,000, 88,000, and 100,000 can be identified in extracts of cells infected by wild-type virus. After exposure of cells to Nonidet P-40, the 85,000- and 88,000-dalton proteins were found in varying amounts in extracts of permissive cells but not in extracts of transformed cells. This finding raised the question of the possible functional importance of the smaller proteins in productive infection. However, the virtual absence of the 85,000- and 88,000-dalton proteins in some extracts of the fully permissive CV-1 cell line indicates that a conversion of the larger to the smaller forms of the A protein is not required in significant quantity for productive infection. Furthermore, a study of extraction conditions shows that the smaller proteins are easily generated during extraction and provides an explanation for the appearance of these proteins in some cells after extraction under unfavorable conditions.", "contents": "Modification of simian virus 40 protein A. The A protein of simian virus 40 is phosphorylated in both productive and transforming infection. The phosphorylated amino acid has been identified as serine and has been localized in a single tryptic peptide of the protein. Because the A protein synthesized in infection by A mutants is phosphorylated to the same extent and in the same peptide as in infection by wild-type virus, the functional defect of the A mutants is apparently unrelated to phosphorylation. At least three distinct forms of the A protein with apparent molecular weights of 85,000, 88,000, and 100,000 can be identified in extracts of cells infected by wild-type virus. After exposure of cells to Nonidet P-40, the 85,000- and 88,000-dalton proteins were found in varying amounts in extracts of permissive cells but not in extracts of transformed cells. This finding raised the question of the possible functional importance of the smaller proteins in productive infection. However, the virtual absence of the 85,000- and 88,000-dalton proteins in some extracts of the fully permissive CV-1 cell line indicates that a conversion of the larger to the smaller forms of the A protein is not required in significant quantity for productive infection. Furthermore, a study of extraction conditions shows that the smaller proteins are easily generated during extraction and provides an explanation for the appearance of these proteins in some cells after extraction under unfavorable conditions."}
{"id": "PMID:189093", "title": "Giant heterogeneous polyadenylic acid on vesicular stomatitis virus mRNA synthesized in vitro in the presence of S-adenosylhomocysteine.", "content": "An in vitro transcription system in which vesicular stomatitis virus (VSV) mRNA species have been synthesized is described. In addition to purified VSV virions, which contain an RNA-dependent RNA polymerase, this system contained a cytoplasmic cell extract that enhanced correct transcription. Gel electrophoretic analysis of the methylated polyadenylic acid [poly(A)]-containing VSV mRNA produced in this system in the presenct of S-adenosylmethionine showed the discrete VSV mRNA species. However, when unmethylated mRNA was synthesized in the presence of S-adenosylhomocysteine, the poly(A)-containing transcripts were large and heterogeneous in molecular weight and did not contain discrete VSV mRNA species. Two-dimensional fingerprint analysis of the methylated and unmethylated products suggested that identical nucleotide sequences were present in the RNAs. Further analysis showed the presence of very large heterogeneous poly(A), 200 to 2,000 nucleotides in lenght, in the unmethylated transcript. Proof that this large poly(A) was covalently linked to the correct VSV mRNA transcripts was obtained by removal of the poly(A) by hybirdization with oligodeoxythymidylic acid and digestion with RNase H. This digestion produced unmethylated VSV mRNA transcripts with the same discrete sizes as the deadenylated RNAs produced from VSV mRNA initially isolated from VSV-infected cells. The results suggest that there is a relationship between methylation at the 5'-end and polyadenylation at the 3'-end of VSV mRNA's. Furthermore, addition of the very large poly(A) does not affect the normal process of sequential transcription of the VSV genome, suggesting that this poly(A) addition is occurring independently of further transcription.", "contents": "Giant heterogeneous polyadenylic acid on vesicular stomatitis virus mRNA synthesized in vitro in the presence of S-adenosylhomocysteine. An in vitro transcription system in which vesicular stomatitis virus (VSV) mRNA species have been synthesized is described. In addition to purified VSV virions, which contain an RNA-dependent RNA polymerase, this system contained a cytoplasmic cell extract that enhanced correct transcription. Gel electrophoretic analysis of the methylated polyadenylic acid [poly(A)]-containing VSV mRNA produced in this system in the presenct of S-adenosylmethionine showed the discrete VSV mRNA species. However, when unmethylated mRNA was synthesized in the presence of S-adenosylhomocysteine, the poly(A)-containing transcripts were large and heterogeneous in molecular weight and did not contain discrete VSV mRNA species. Two-dimensional fingerprint analysis of the methylated and unmethylated products suggested that identical nucleotide sequences were present in the RNAs. Further analysis showed the presence of very large heterogeneous poly(A), 200 to 2,000 nucleotides in lenght, in the unmethylated transcript. Proof that this large poly(A) was covalently linked to the correct VSV mRNA transcripts was obtained by removal of the poly(A) by hybirdization with oligodeoxythymidylic acid and digestion with RNase H. This digestion produced unmethylated VSV mRNA transcripts with the same discrete sizes as the deadenylated RNAs produced from VSV mRNA initially isolated from VSV-infected cells. The results suggest that there is a relationship between methylation at the 5'-end and polyadenylation at the 3'-end of VSV mRNA's. Furthermore, addition of the very large poly(A) does not affect the normal process of sequential transcription of the VSV genome, suggesting that this poly(A) addition is occurring independently of further transcription."}
{"id": "PMID:189094", "title": "Evidence that a precursor glycoprotein is cleaved to yield the major glycoprotein of avian tumor virus.", "content": "A glycoprotein designated pr90, which is recognized by anti-gp85 serum, is present in lysates of pulse-labeled transformed cells. Under chase conditions, a reduction in the level of labeled pr90 is observed concomitant with the appearance of labeled, cell-associated viral glycoprotein.", "contents": "Evidence that a precursor glycoprotein is cleaved to yield the major glycoprotein of avian tumor virus. A glycoprotein designated pr90, which is recognized by anti-gp85 serum, is present in lysates of pulse-labeled transformed cells. Under chase conditions, a reduction in the level of labeled pr90 is observed concomitant with the appearance of labeled, cell-associated viral glycoprotein."}
{"id": "PMID:189095", "title": "Cyclic AMP regulation of mammary tumor virus production.", "content": "Addition of dibutyryl cyclic AMP (cAMP) and agents (isoproterenol and epinephrine) that stimulate the activities of adenylate cyclase enhance the stimulation  of mammary tumor virus (MTV) production two- to threefold by glucocorticoid in short-term primary cultures of mammary tumors. This cAMP potentiation seems to depend on the stimulated level of MTV production by glucocorticoid alone, which increases MTV production 5- to 10-fold over basal level but varies greatly in absolute terms. When the stimulated level by glucocorticoid alone is suboptimal, cAMP seems to restore the sensitivity of the cells to the stimulatory effect of glucocorticoid to its maximum.", "contents": "Cyclic AMP regulation of mammary tumor virus production. Addition of dibutyryl cyclic AMP (cAMP) and agents (isoproterenol and epinephrine) that stimulate the activities of adenylate cyclase enhance the stimulation  of mammary tumor virus (MTV) production two- to threefold by glucocorticoid in short-term primary cultures of mammary tumors. This cAMP potentiation seems to depend on the stimulated level of MTV production by glucocorticoid alone, which increases MTV production 5- to 10-fold over basal level but varies greatly in absolute terms. When the stimulated level by glucocorticoid alone is suboptimal, cAMP seems to restore the sensitivity of the cells to the stimulatory effect of glucocorticoid to its maximum."}
{"id": "PMID:189096", "title": "5' termini of poliovirus RNA: difference between virion and nonencapsidated 35S RNA.", "content": "Poliovirus cytoplasmic, nonencapsidated 35S RNA yields approximately one pUp per molecule upon T2 RNase digestion, indicating that this RNA has the same 5' end as the polyribosome-associated viral RNA fraction. Double-stranded, replicative form RNA after the same treatment yielded approximately four pNp structures per molecule, 65% of which was pUp. In contrast, the 35S RNA from mature virions contained no detectable pNp, indicating that the 5' end of the virion RNA is different from that of the nonencapsidated RNA. None of the above molecules contained pppNp, ppNp, or GpppNp structures present in host mRNA. The virion RNA molecules, as we have shown previously for thenonencapsidated 35S viral RNA (Fernandez-Mu\u00f1oz and Darnell, 1976), is not labeled with [methyl-3H]methionine.", "contents": "5' termini of poliovirus RNA: difference between virion and nonencapsidated 35S RNA. Poliovirus cytoplasmic, nonencapsidated 35S RNA yields approximately one pUp per molecule upon T2 RNase digestion, indicating that this RNA has the same 5' end as the polyribosome-associated viral RNA fraction. Double-stranded, replicative form RNA after the same treatment yielded approximately four pNp structures per molecule, 65% of which was pUp. In contrast, the 35S RNA from mature virions contained no detectable pNp, indicating that the 5' end of the virion RNA is different from that of the nonencapsidated RNA. None of the above molecules contained pppNp, ppNp, or GpppNp structures present in host mRNA. The virion RNA molecules, as we have shown previously for thenonencapsidated 35S viral RNA (Fernandez-Mu\u00f1oz and Darnell, 1976), is not labeled with [methyl-3H]methionine."}
{"id": "PMID:189097", "title": "Cyclic adenosine monophosphate: relationship to calcium metabolism and renal lithiasis.", "content": "Recent concepts in calcium metabolism are being applied to the renal stone-forming patient. As our understanding of physiological mechanisms improves urinary cyclic nucleotide determinations are becoming useful in applied patient care. The changes in urinary cyclic adenosine monophosphate excretion as related to the different forms of hypercalciuria are reviewed.", "contents": "Cyclic adenosine monophosphate: relationship to calcium metabolism and renal lithiasis. Recent concepts in calcium metabolism are being applied to the renal stone-forming patient. As our understanding of physiological mechanisms improves urinary cyclic nucleotide determinations are becoming useful in applied patient care. The changes in urinary cyclic adenosine monophosphate excretion as related to the different forms of hypercalciuria are reviewed."}
{"id": "PMID:189098", "title": "Testicular lymphography: clinical study.", "content": "Direct injection of lipiodol into the parenchyma of the human testis to study retroperitoneal lymphatics and lymph nodes is a potentially dangerous investigation. The information obtained with this study is incomplete and far inferior when compared to results obtained with standard procedures, such as pedal lymphography or cannulation of testicular lymphatics.", "contents": "Testicular lymphography: clinical study. Direct injection of lipiodol into the parenchyma of the human testis to study retroperitoneal lymphatics and lymph nodes is a potentially dangerous investigation. The information obtained with this study is incomplete and far inferior when compared to results obtained with standard procedures, such as pedal lymphography or cannulation of testicular lymphatics."}
{"id": "PMID:189099", "title": "Infectious mononucleosis in children. Evaluation of Epstein-Barr virus-specific serological data.", "content": "Epstein-Barr virus (EBV)-specific antibody responses were determined in 43 consecutive pediatric patients who had signs and symptoms of inectious mononucleosis (IM) and positive diagnostic tests for mononucleosis (Monspot). Thirty patients gave clear-cut serologic evidence of primary EBV infections; of the remaining 13 patients, seven had no antibodies to EBV in the acute- or convalescent-phase sera and six showed serologic patterns of past EBV infections. Further testing proved that the initial Monospot results were either false-positive or were incorrectly interpreted in all 13 patients with unidentifiable illnesses but in only two of the patients with current EBV infections. The data confirm the occurrence of classical IM in children and show that the disease and the EBV-specific antibody responses can be virtually indistinguishable from adult cases.", "contents": "Infectious mononucleosis in children. Evaluation of Epstein-Barr virus-specific serological data. Epstein-Barr virus (EBV)-specific antibody responses were determined in 43 consecutive pediatric patients who had signs and symptoms of inectious mononucleosis (IM) and positive diagnostic tests for mononucleosis (Monspot). Thirty patients gave clear-cut serologic evidence of primary EBV infections; of the remaining 13 patients, seven had no antibodies to EBV in the acute- or convalescent-phase sera and six showed serologic patterns of past EBV infections. Further testing proved that the initial Monospot results were either false-positive or were incorrectly interpreted in all 13 patients with unidentifiable illnesses but in only two of the patients with current EBV infections. The data confirm the occurrence of classical IM in children and show that the disease and the EBV-specific antibody responses can be virtually indistinguishable from adult cases."}
{"id": "PMID:189106", "title": "Nasopharyngeal carcinoma and Epstein-Barr virus. III. The detection of anti-nuclear antibodies.", "content": "The presence of anti-nuclear antibodies (ANA) has been studied in 433 sera from 305 patients with anaplastic nasopharyngeal carcinoma (NPC) in Taiwan, by means of indirect fluorescent antibody method. Another 134 sera from normal adults or from patients with other diseases served as controls. Patients with NPC showed positive rate of 23.1%. Forty-two patients with other malignant and 25 patients with benign tumors of the head and neck showed positive rates of 9.5% and 8.0%, respectively. Forty-eight patients with inflammatory diseases and 19 normal adults were negative. The presence of ANA in 103 NPC patients before treatment was analyzed in detail. The positive rate was not significantly influenced by the age and sex of the patients, by the duration of the disease, by the extent of primary tumor and the presence of neck metastasis. But the positive rate rose as the anti-EB-VCA titer increased. This positive correlation of ANA and anti-EB-VCA antibodies was also significant in all the NPC sera. During and at the end of irradiation therapy, the ANA positive rates showed no remarkable variation. After treatment of the disease, ANA positive rate decreased gradually and this reduction became apparent after three years of remission of the disease. But the presence of ANA in NPC patients was not related to the prognosis of the patients. The possible mechanism in production of ANA in NPC patients was discussed with special reference to EB virus.", "contents": "Nasopharyngeal carcinoma and Epstein-Barr virus. III. The detection of anti-nuclear antibodies. The presence of anti-nuclear antibodies (ANA) has been studied in 433 sera from 305 patients with anaplastic nasopharyngeal carcinoma (NPC) in Taiwan, by means of indirect fluorescent antibody method. Another 134 sera from normal adults or from patients with other diseases served as controls. Patients with NPC showed positive rate of 23.1%. Forty-two patients with other malignant and 25 patients with benign tumors of the head and neck showed positive rates of 9.5% and 8.0%, respectively. Forty-eight patients with inflammatory diseases and 19 normal adults were negative. The presence of ANA in 103 NPC patients before treatment was analyzed in detail. The positive rate was not significantly influenced by the age and sex of the patients, by the duration of the disease, by the extent of primary tumor and the presence of neck metastasis. But the positive rate rose as the anti-EB-VCA titer increased. This positive correlation of ANA and anti-EB-VCA antibodies was also significant in all the NPC sera. During and at the end of irradiation therapy, the ANA positive rates showed no remarkable variation. After treatment of the disease, ANA positive rate decreased gradually and this reduction became apparent after three years of remission of the disease. But the presence of ANA in NPC patients was not related to the prognosis of the patients. The possible mechanism in production of ANA in NPC patients was discussed with special reference to EB virus."}
{"id": "PMID:189107", "title": "In vitro aggregation of platelets induced by alpha-toxin (phospholipase C) of Clostridium perfringens.", "content": "Highly purified alpha-toxin (phospholipase C) of Clostridium perfringens prepared by affinity chromatography on agarose-linked egg-yolk lipoprotein induced the in vitro aggregation of platelets of an irreversible type. The aggregation started after a time lag, the length of which depended on the concentration of the toxin; the reciprocal of the time lag was found to be directly proportional to the toxin concentration. Using this assay method, we demonstrated that the platelet-aggregating activity of alpha-toxin reached minimum at around 70 C but heating at higher temperatures inactivated it to a lesser extent; the same anomaly in heat inactivation was observed with phospholipase C activity possessed by the toxin. By subjecting purified alpha-toxin to isoelectric focusing, four molecular forms were isolated, all of which were associated with both the platelet-aggregating and phospholipase C activities. From all these results we concluded that the entity responsible for the platelet-aggregating activity is identical with alpha-toxin (phospholipase C).", "contents": "In vitro aggregation of platelets induced by alpha-toxin (phospholipase C) of Clostridium perfringens. Highly purified alpha-toxin (phospholipase C) of Clostridium perfringens prepared by affinity chromatography on agarose-linked egg-yolk lipoprotein induced the in vitro aggregation of platelets of an irreversible type. The aggregation started after a time lag, the length of which depended on the concentration of the toxin; the reciprocal of the time lag was found to be directly proportional to the toxin concentration. Using this assay method, we demonstrated that the platelet-aggregating activity of alpha-toxin reached minimum at around 70 C but heating at higher temperatures inactivated it to a lesser extent; the same anomaly in heat inactivation was observed with phospholipase C activity possessed by the toxin. By subjecting purified alpha-toxin to isoelectric focusing, four molecular forms were isolated, all of which were associated with both the platelet-aggregating and phospholipase C activities. From all these results we concluded that the entity responsible for the platelet-aggregating activity is identical with alpha-toxin (phospholipase C)."}
{"id": "PMID:189108", "title": "Comparative investigations of alpha- and beta-effects on the longitudinal and circular muscles of the pregnant rat myometrium.", "content": "Comparative effects of noradrenaline (10(-8)-10(-6) g/ml) and isoprenaline (10(-10)-10(-6) g/ml) on electrical and contractile activity were investigated in longitudinal and circular muscle strips of rat myometrium (13-19 days pregnant). When recorded with an intracellular microelectrode, spike potentials of longitudinal muscle discharged spontaneously in bursts. Treatment with either noradrenaline or isoprenaline hyperpolarized the membrane and increased membrane conductance, causing the cessation of spontaneous activity. Slow potential was dominant in the circular muscle, and it became prolonged after treatment with noradrenaline, leading to an increase in tension. Isoprenaline reduced the duration of the slow potential and depressed the contraction. The minimal concentration of isoprenaline needed to suppress the spontaneous activity in circular muscle was much higher than in longitudinal muscle. The excitatory effect of noradrenaline on circular muscle was antagonized by treatment with phentolamine, and the inhibitory effect of catecholamines on both longitudinal and circular muscles by propranolol. alpha-Adrenoceptor appears predominant in circular muscle, while beta-adrenoceptor in longitudinal muscle in rat myometrium during late-pregnancy.", "contents": "Comparative investigations of alpha- and beta-effects on the longitudinal and circular muscles of the pregnant rat myometrium. Comparative effects of noradrenaline (10(-8)-10(-6) g/ml) and isoprenaline (10(-10)-10(-6) g/ml) on electrical and contractile activity were investigated in longitudinal and circular muscle strips of rat myometrium (13-19 days pregnant). When recorded with an intracellular microelectrode, spike potentials of longitudinal muscle discharged spontaneously in bursts. Treatment with either noradrenaline or isoprenaline hyperpolarized the membrane and increased membrane conductance, causing the cessation of spontaneous activity. Slow potential was dominant in the circular muscle, and it became prolonged after treatment with noradrenaline, leading to an increase in tension. Isoprenaline reduced the duration of the slow potential and depressed the contraction. The minimal concentration of isoprenaline needed to suppress the spontaneous activity in circular muscle was much higher than in longitudinal muscle. The excitatory effect of noradrenaline on circular muscle was antagonized by treatment with phentolamine, and the inhibitory effect of catecholamines on both longitudinal and circular muscles by propranolol. alpha-Adrenoceptor appears predominant in circular muscle, while beta-adrenoceptor in longitudinal muscle in rat myometrium during late-pregnancy."}
{"id": "PMID:189109", "title": "Effects of disulfide bond reduction on the excitatory and inhibitory postsynaptic responses of Aplysia ganglion cells.", "content": "Three kinds of the cholinoceptive neurons, nicotinic depolarizing (D)-, nicotinic hyperpolarizing (H)-, and muscarinic H-tyes, as well as two other kinds of neurons, GABA H- and dopamine H-types, were identified in Aplysia abdominal ganglion, and the effects of disulfide bond reduction and reoxidation on their postsynape acetylcholine-induced responses of both nicotinic types (D- and H-) were depressed by reducing the disulfide bonds with dithiothreitol (DTT) and restored by reoxidizing with 5, 5' -dithiobis-(2-nitrobenzoic acid): (DTNB), whereas the responses of the muscarinic H-, GABA H-, and dopamine H-cells were not affected at all by either DTT or DTNB. In contrast to the results obtained from the electroplax, the cholinergic receptors in our preparation showed neither the activation by hexamethonium nor the augmentation of decamethonium-induced responses after reduction of disulfide bonds. In addition, our preparation did not demonstrate the long-lasting responses to bromoaTT-induced depression of the nicotinic responses was studied on the dose-response curves; the mode of receptor inhibition was rather complexed, being neither type of competitive nor non-competitive. We concluded that the disulfide bond is a crucial element in both types of nicotinic receptors (D and H), and that this bond is related to the activation process of the receptors regardless of their ionic specificities.", "contents": "Effects of disulfide bond reduction on the excitatory and inhibitory postsynaptic responses of Aplysia ganglion cells. Three kinds of the cholinoceptive neurons, nicotinic depolarizing (D)-, nicotinic hyperpolarizing (H)-, and muscarinic H-tyes, as well as two other kinds of neurons, GABA H- and dopamine H-types, were identified in Aplysia abdominal ganglion, and the effects of disulfide bond reduction and reoxidation on their postsynape acetylcholine-induced responses of both nicotinic types (D- and H-) were depressed by reducing the disulfide bonds with dithiothreitol (DTT) and restored by reoxidizing with 5, 5' -dithiobis-(2-nitrobenzoic acid): (DTNB), whereas the responses of the muscarinic H-, GABA H-, and dopamine H-cells were not affected at all by either DTT or DTNB. In contrast to the results obtained from the electroplax, the cholinergic receptors in our preparation showed neither the activation by hexamethonium nor the augmentation of decamethonium-induced responses after reduction of disulfide bonds. In addition, our preparation did not demonstrate the long-lasting responses to bromoaTT-induced depression of the nicotinic responses was studied on the dose-response curves; the mode of receptor inhibition was rather complexed, being neither type of competitive nor non-competitive. We concluded that the disulfide bond is a crucial element in both types of nicotinic receptors (D and H), and that this bond is related to the activation process of the receptors regardless of their ionic specificities."}
{"id": "PMID:189110", "title": "Experimental study on renal and hepatic glucose metabolism in total gastrectomized dogs with special reference to glycolysis and glyconeogenesis.", "content": "In spite of the extensive studies on glucose metabolism in surgical field, the postoperative renal and hepatic glucose metabolism and their interrelation have not been reported. The present study was undertaken to interrelate the metabolic states in the kidney and the liver in total gastrectomized dogs. In the kidney, the glycolysis was inhibited in the early postoperative stage whereas the gluconeogenesis was activated. In the late postoperative stage the glycolysis remained slightly inhibited, while the gluconeogenesis remained activated. In the liver, in the early postoperative stage the glycolysis was inhibited, whereas the gluconeogenesis was activated. The glycolysis in the late postoperative stage returned to the preoperative stage, while the gluconeogenesis remained inhibited. The gluconeogenesis in both kidney and liver was disturbed in the early postoperative stage while they were restored, but were reversed, in the late postoperative stage.", "contents": "Experimental study on renal and hepatic glucose metabolism in total gastrectomized dogs with special reference to glycolysis and glyconeogenesis. In spite of the extensive studies on glucose metabolism in surgical field, the postoperative renal and hepatic glucose metabolism and their interrelation have not been reported. The present study was undertaken to interrelate the metabolic states in the kidney and the liver in total gastrectomized dogs. In the kidney, the glycolysis was inhibited in the early postoperative stage whereas the gluconeogenesis was activated. In the late postoperative stage the glycolysis remained slightly inhibited, while the gluconeogenesis remained activated. In the liver, in the early postoperative stage the glycolysis was inhibited, whereas the gluconeogenesis was activated. The glycolysis in the late postoperative stage returned to the preoperative stage, while the gluconeogenesis remained inhibited. The gluconeogenesis in both kidney and liver was disturbed in the early postoperative stage while they were restored, but were reversed, in the late postoperative stage."}
{"id": "PMID:189112", "title": "Autonomous peripheral nerve activity causing generalized muscle stiffness and fasciculations: report of a case with physiological, pharmacological, and morphological observations.", "content": "A 14-year-old boy with generalized muscle weakness, stiffness and fasciculations associated with profuse and continuous electromyographic (EMG) activity is described. The spontaneous mechanical and electrical muscle activity was unaffected by sleep, general anesthesia, or spinal anesthesia but was abolished by small doses of curare, succinyl-choline, and gallamine. Proximal and distal peripheral nerve block caused moderate and marked reduction of EMG activity, respectively, thus indicating that the disorder is due to autonomous peripheral nerve activity. The delayed motor nerve conduction velocities and the structural abnormalities seen in some of the myelin sheaths by light and electron microscopic studies on sural nerve biopsy preparations constitute further evidence that the peripheral nerve is the site of abnormality in this disorder. Diphenyl hydantoin and carbamazepine maintenance therapy produced adequate clinical relief.", "contents": "Autonomous peripheral nerve activity causing generalized muscle stiffness and fasciculations: report of a case with physiological, pharmacological, and morphological observations. A 14-year-old boy with generalized muscle weakness, stiffness and fasciculations associated with profuse and continuous electromyographic (EMG) activity is described. The spontaneous mechanical and electrical muscle activity was unaffected by sleep, general anesthesia, or spinal anesthesia but was abolished by small doses of curare, succinyl-choline, and gallamine. Proximal and distal peripheral nerve block caused moderate and marked reduction of EMG activity, respectively, thus indicating that the disorder is due to autonomous peripheral nerve activity. The delayed motor nerve conduction velocities and the structural abnormalities seen in some of the myelin sheaths by light and electron microscopic studies on sural nerve biopsy preparations constitute further evidence that the peripheral nerve is the site of abnormality in this disorder. Diphenyl hydantoin and carbamazepine maintenance therapy produced adequate clinical relief."}
{"id": "PMID:189113", "title": "Ambient temperature of hypoxia: a differential study of liver catalase and cytochrome oxidase in guinea pig.", "content": "The activities of liver catalase and cytochrome oxidase have been determined in sea-level and high-altitude native guinea pigs exposed to different ambient temperatures. The activities of both of these enzymatic systems have been found to increase as ambient temperature is reduced, and this occurs in the sea-level and the high-altitude animals. At equal temperatures, cytochrome oxidase activity is identical in the liver of guinea pigs from sea-level and high-altitude. Catalase activity is approximately 50% lower in the high-altitude animals than in the sea-level ones maintained at the same ambient temperature. It is necessary to reassess current data on hypoxia-induced enzymatic and hormonal changes measured under conditions where the ambient temperature was not controlled, especially in those cases involving volunteer human subjects.", "contents": "Ambient temperature of hypoxia: a differential study of liver catalase and cytochrome oxidase in guinea pig. The activities of liver catalase and cytochrome oxidase have been determined in sea-level and high-altitude native guinea pigs exposed to different ambient temperatures. The activities of both of these enzymatic systems have been found to increase as ambient temperature is reduced, and this occurs in the sea-level and the high-altitude animals. At equal temperatures, cytochrome oxidase activity is identical in the liver of guinea pigs from sea-level and high-altitude. Catalase activity is approximately 50% lower in the high-altitude animals than in the sea-level ones maintained at the same ambient temperature. It is necessary to reassess current data on hypoxia-induced enzymatic and hormonal changes measured under conditions where the ambient temperature was not controlled, especially in those cases involving volunteer human subjects."}
{"id": "PMID:189116", "title": "[Functional state of the cortical and medullary layers of the adrenals in primary arterial hypotension].", "content": "The functional state of the cortical and medullar layers of the adrenal glands was studied in 127 patients with primary arterial hypotension (109 females and 18 males, aged 17 to 48 years). As shown by daily urine excretion, hypotonic patients had a decreased basal activity of the glucocorticoid and androgenic function of the adrenal cortex in comparison with those in normal individuals. The potential of the adrenal cortex was preserved in these patients within sufficient limits. The adrenocorticotrophic function of the anterior lobe of the pituitary gland was found to decrease. Against the background of a reduction of the total excretion of all fractions a relative delay was noted in the process of glucocorticoids transformation into their precursors, as well as a relative predominance of glucocorticoids over mineralcorticoids, the content of desoxycorticosterone being reduced especially low. The content of adrenalin, noradrenaline and dophamine was below the normal level, the decrease being statistically significant. At the same time the excretion of DOPA was normal, on the average, the whole group of patients. The changes in the daily urine excretion of catecholamines and DOPA, as well as in their ratio indicate that the activity of both links of the sympathodrenal system is reduced in primary arterial hypotension.", "contents": "[Functional state of the cortical and medullary layers of the adrenals in primary arterial hypotension]. The functional state of the cortical and medullar layers of the adrenal glands was studied in 127 patients with primary arterial hypotension (109 females and 18 males, aged 17 to 48 years). As shown by daily urine excretion, hypotonic patients had a decreased basal activity of the glucocorticoid and androgenic function of the adrenal cortex in comparison with those in normal individuals. The potential of the adrenal cortex was preserved in these patients within sufficient limits. The adrenocorticotrophic function of the anterior lobe of the pituitary gland was found to decrease. Against the background of a reduction of the total excretion of all fractions a relative delay was noted in the process of glucocorticoids transformation into their precursors, as well as a relative predominance of glucocorticoids over mineralcorticoids, the content of desoxycorticosterone being reduced especially low. The content of adrenalin, noradrenaline and dophamine was below the normal level, the decrease being statistically significant. At the same time the excretion of DOPA was normal, on the average, the whole group of patients. The changes in the daily urine excretion of catecholamines and DOPA, as well as in their ratio indicate that the activity of both links of the sympathodrenal system is reduced in primary arterial hypotension."}
{"id": "PMID:189117", "title": "[State of the neurohumoral regulatory system in circulatory insufficiency].", "content": "A moderate elevation of the daily excretion of free noradrenaline and adrenalin is observed in chronic circulatory insufficiency, beginning with Stage IIA. The catecholamines metabolism is elevated, as shown by the daily excretion of normethanpherine and methanpherine and of vanillyl-mandelic acid. The activity of renin and angiotensinases was growing along with the progressing cardiac insufficiency. The blood level of angiotensinogen was decreasing, especially in patients with Stage IIB and III of decompensation. The daily excretion of aldosterone was growing along with the development of cardiac insufficiency. The functional state of the glucocorticoid function of the adrenal cortex was of a phased nature in cases of circulatory insufficiency. The study of the functional state of the epiphysis was conducted by way of determining the blood level of melatonine and of its daily excretion. In Stages I and IIA the level of this hormone was clearly elevated, in Stages IIB and III -- decreased as compared with the initial and normal levels. The plasma level of the antidiuretic hormone was distinctly growing, beginning with Stage IIB, reaching its maximal values in Stage III.", "contents": "[State of the neurohumoral regulatory system in circulatory insufficiency]. A moderate elevation of the daily excretion of free noradrenaline and adrenalin is observed in chronic circulatory insufficiency, beginning with Stage IIA. The catecholamines metabolism is elevated, as shown by the daily excretion of normethanpherine and methanpherine and of vanillyl-mandelic acid. The activity of renin and angiotensinases was growing along with the progressing cardiac insufficiency. The blood level of angiotensinogen was decreasing, especially in patients with Stage IIB and III of decompensation. The daily excretion of aldosterone was growing along with the development of cardiac insufficiency. The functional state of the glucocorticoid function of the adrenal cortex was of a phased nature in cases of circulatory insufficiency. The study of the functional state of the epiphysis was conducted by way of determining the blood level of melatonine and of its daily excretion. In Stages I and IIA the level of this hormone was clearly elevated, in Stages IIB and III -- decreased as compared with the initial and normal levels. The plasma level of the antidiuretic hormone was distinctly growing, beginning with Stage IIB, reaching its maximal values in Stage III."}
{"id": "PMID:189119", "title": "[Effect of antikinin agents on the course of experimental myocarditis].", "content": "The therapeutic action of 5 preparations: specific antikinin substances -- anginin and contrical, and nonspecific -- epsilon-aminocapronic acid, aspirin and indometacine, was tested in 71 rabbits with allergic myocarditis. It has been concluded that in the allergic distruction of the myocardium plasma kinins, which are formed and accumulated in large quantities, take part in the pathogenesis of the disease serving as mediators of the tissue distruction, therefore specific antagonists of kinins and inhibitors of the kinin system should be included as pathogenetic agents into the complex of allergic myocarditis treatment.", "contents": "[Effect of antikinin agents on the course of experimental myocarditis]. The therapeutic action of 5 preparations: specific antikinin substances -- anginin and contrical, and nonspecific -- epsilon-aminocapronic acid, aspirin and indometacine, was tested in 71 rabbits with allergic myocarditis. It has been concluded that in the allergic distruction of the myocardium plasma kinins, which are formed and accumulated in large quantities, take part in the pathogenesis of the disease serving as mediators of the tissue distruction, therefore specific antagonists of kinins and inhibitors of the kinin system should be included as pathogenetic agents into the complex of allergic myocarditis treatment."}
{"id": "PMID:189132", "title": "Acceleration and weakness in parkinsonian dysarthria.", "content": "This report presents some of the underlying neuromuscular mechanisms of dysarthric speech production as they are manifested in selected individuals with parkinsonism. Earlier explanations of parkinsonian dysarthria emphasized that the balanced hypertonus of rigidity formed the basis of reduced range of movements in speech. The present data reveal two problems in the neuromuscular control signals that can result in a reduced range of speech movements in the absence of rigidity. These neuromuscular problems are described as acceleration and weakness. The implication of these findings for the evaluation and treatment of parkinsonian dysarthria is discussed.", "contents": "Acceleration and weakness in parkinsonian dysarthria. This report presents some of the underlying neuromuscular mechanisms of dysarthric speech production as they are manifested in selected individuals with parkinsonism. Earlier explanations of parkinsonian dysarthria emphasized that the balanced hypertonus of rigidity formed the basis of reduced range of movements in speech. The present data reveal two problems in the neuromuscular control signals that can result in a reduced range of speech movements in the absence of rigidity. These neuromuscular problems are described as acceleration and weakness. The implication of these findings for the evaluation and treatment of parkinsonian dysarthria is discussed."}
{"id": "PMID:189135", "title": "Effect of ethanol on the cyclic AMP system in rat brain.", "content": "The effects of ethanol on adenylate cyclase and phosphodiesterase activity in vitro, and on cyclic AMP, ATP and adenosine levels in vivo were studied. Ethanol appeared to affect the cyclic AMP system indirectly, probably through its effect on neurotransmitter release or on adenosine formation.", "contents": "Effect of ethanol on the cyclic AMP system in rat brain. The effects of ethanol on adenylate cyclase and phosphodiesterase activity in vitro, and on cyclic AMP, ATP and adenosine levels in vivo were studied. Ethanol appeared to affect the cyclic AMP system indirectly, probably through its effect on neurotransmitter release or on adenosine formation."}
{"id": "PMID:189139", "title": "Differentiation and aging of the intestinal mucosa of the rat. I. Morphological, enzyme-histochemical and disc electrophoretic aspects of the prenatal and postnatal differentiation of the intestinal mucosa.", "content": "The large and small intestines of fetal, newborn, juvenile and adult rats were investigated at various points by means of enzyme histochemistry, disc electrophoretic separations of enzymes and electron microscopy. The results obtained permit division of the morphological and enzymatic differentiation of the rat intestinal epithelium into four periods of development. 1. The period of prenatal development from the 19th to the 21st fetal day with a continuous increase of the enzyme activities in the enterocytes of the entire intestinal mucosa. 2. The period of postnatal development from the first day of life until the end of the second week with enzyme activity remaining roughly the same compared with the 21st day of life. 3. The period of adaptation from the beginning of the third week of life up to the middle of the fourth week of life. During this phase the transition into the stage of adult maturity occurs both morphologically and enzymatically. 4. The stage of adult maturity, which is fully developed in the middle of the fourth week of life.", "contents": "Differentiation and aging of the intestinal mucosa of the rat. I. Morphological, enzyme-histochemical and disc electrophoretic aspects of the prenatal and postnatal differentiation of the intestinal mucosa. The large and small intestines of fetal, newborn, juvenile and adult rats were investigated at various points by means of enzyme histochemistry, disc electrophoretic separations of enzymes and electron microscopy. The results obtained permit division of the morphological and enzymatic differentiation of the rat intestinal epithelium into four periods of development. 1. The period of prenatal development from the 19th to the 21st fetal day with a continuous increase of the enzyme activities in the enterocytes of the entire intestinal mucosa. 2. The period of postnatal development from the first day of life until the end of the second week with enzyme activity remaining roughly the same compared with the 21st day of life. 3. The period of adaptation from the beginning of the third week of life up to the middle of the fourth week of life. During this phase the transition into the stage of adult maturity occurs both morphologically and enzymatically. 4. The stage of adult maturity, which is fully developed in the middle of the fourth week of life."}
{"id": "PMID:189140", "title": "Effect of aging on cyclic AMP levels and adenylate cyclase and phosphodiesterase activities in the rat corpus striatum.", "content": "Cyclic AMP levels and activities of adenylate cyclase and phosphodiesterase in the striatum were measured in 4, 12, 24 and 30 month-old rats. No age-related changes were observed either in cyclic AMP levels or basal adenylate cyclase activity. However, there was an age-related decline in dopamine sensitivity of adenylate cyclase without affecting NaF-induced stimulation. There was also an age-dependent decrease in phosphodiesterase activity at low substrate concentrations (3 X 10(-7) and 3 X 10(-6) M) but not at high substrate concentrations (3 X 10(-5) and 3 X 10(-4) M). These results suggest that the functions of dopaminergic neurons may have been altered by aging.", "contents": "Effect of aging on cyclic AMP levels and adenylate cyclase and phosphodiesterase activities in the rat corpus striatum. Cyclic AMP levels and activities of adenylate cyclase and phosphodiesterase in the striatum were measured in 4, 12, 24 and 30 month-old rats. No age-related changes were observed either in cyclic AMP levels or basal adenylate cyclase activity. However, there was an age-related decline in dopamine sensitivity of adenylate cyclase without affecting NaF-induced stimulation. There was also an age-dependent decrease in phosphodiesterase activity at low substrate concentrations (3 X 10(-7) and 3 X 10(-6) M) but not at high substrate concentrations (3 X 10(-5) and 3 X 10(-4) M). These results suggest that the functions of dopaminergic neurons may have been altered by aging."}
{"id": "PMID:189141", "title": "An effect of age on the phosphodiesterase activator protein of rat cerebral cortex. A brief note.", "content": "Measurements were made of the effectiveness of phosphodiesterase activator protein isolated from the cerebral cortex of rats of various ages in stimulating the phosphodiesterase-catalyzed conversion of cyclic-AMP into 5'-AMP. An age dependent increase in the potency of preparations of activator protein was observed, with the activator isolated from animals six months of age and older being generally more efficacious than that from younger animals.", "contents": "An effect of age on the phosphodiesterase activator protein of rat cerebral cortex. A brief note. Measurements were made of the effectiveness of phosphodiesterase activator protein isolated from the cerebral cortex of rats of various ages in stimulating the phosphodiesterase-catalyzed conversion of cyclic-AMP into 5'-AMP. An age dependent increase in the potency of preparations of activator protein was observed, with the activator isolated from animals six months of age and older being generally more efficacious than that from younger animals."}
{"id": "PMID:189152", "title": "Comparative effect of glucagon, dibutyryl cyclic AMP, and epinephrine on the desaturation and elongation of linoleic acid by rat liver microsomes.", "content": "The effect of glucagon, dibutyryl cyclic adenosine 3',5'-monophosphate, and epinephrine on the biosynthesis of polyunsaturated fatty acids of the linoleic acid family was studied. The incubations were performed with rat liver microsomes and labeled linoleic acid under desaturating and elongating conditions. Under desaturating conditions linoleic acid was converted to gamma-linolenic acid, whereas under elongating conditions it was converted to 20:2omega6. Glucagon, dibutyryl cyclic AMP, and epinephrine decreased the oxidative desaturation of linoleic acid to gamma-linolenic acid while the elongating reaction was not modified in the experimental conditions tested. Consequently, the results support the hypothesis that the oxidative desaturation of linoleic acid to gamma-linolenic acid is the main controllable step in the biosynthesis of polyunsaturated fatty acids of the linoleic acid family in the microsomes.", "contents": "Comparative effect of glucagon, dibutyryl cyclic AMP, and epinephrine on the desaturation and elongation of linoleic acid by rat liver microsomes. The effect of glucagon, dibutyryl cyclic adenosine 3',5'-monophosphate, and epinephrine on the biosynthesis of polyunsaturated fatty acids of the linoleic acid family was studied. The incubations were performed with rat liver microsomes and labeled linoleic acid under desaturating and elongating conditions. Under desaturating conditions linoleic acid was converted to gamma-linolenic acid, whereas under elongating conditions it was converted to 20:2omega6. Glucagon, dibutyryl cyclic AMP, and epinephrine decreased the oxidative desaturation of linoleic acid to gamma-linolenic acid while the elongating reaction was not modified in the experimental conditions tested. Consequently, the results support the hypothesis that the oxidative desaturation of linoleic acid to gamma-linolenic acid is the main controllable step in the biosynthesis of polyunsaturated fatty acids of the linoleic acid family in the microsomes."}
{"id": "PMID:189153", "title": "Response to the hypobetalipoproteinemic agent adamantyloxyphenyl piperidine in hyperlipemic rats.", "content": "The hypobetalipoproteinemic activity of U-41,792 (1-[p-(1-adamantyloxy)-phenyl]-piperidine) is a marked and selective reduction of heparin precipitating lipoproteins (low density plus very low density lipoproteins) in cholesterol-cholic acid induced hypercholesterolemic rats. This activity consists of both a reduction in heparin precipitating lipoproteins (HPL) and an increase in high density lipoproteins that are not precipitated by heparin. The increase in high density lipoproteins is routinely noted by decreases in HPL/cholesterol ratios. The pattern of response following single 100 mg/kg doses of U-418792 was determined. After an I.V. dose was administered in a cottonseed oil emulsion, serum cholesterol levels were reduced, beginning at 8 hr after administration and persisting for 96 hr. Similar results, though delayed somewhat, were obtained after a single oral dose. Activity was accompanied by increases in weight and cholesterol content of livers. After multiple, daily, oral doses, liver weights, total lipids, and cholesterol contents were reduced. Hypobetalipopreteinmeic activity was enhanced by prolonged treatments as demonstrated by analyses of serum obtained weekly throughout 7 wk.", "contents": "Response to the hypobetalipoproteinemic agent adamantyloxyphenyl piperidine in hyperlipemic rats. The hypobetalipoproteinemic activity of U-41,792 (1-[p-(1-adamantyloxy)-phenyl]-piperidine) is a marked and selective reduction of heparin precipitating lipoproteins (low density plus very low density lipoproteins) in cholesterol-cholic acid induced hypercholesterolemic rats. This activity consists of both a reduction in heparin precipitating lipoproteins (HPL) and an increase in high density lipoproteins that are not precipitated by heparin. The increase in high density lipoproteins is routinely noted by decreases in HPL/cholesterol ratios. The pattern of response following single 100 mg/kg doses of U-418792 was determined. After an I.V. dose was administered in a cottonseed oil emulsion, serum cholesterol levels were reduced, beginning at 8 hr after administration and persisting for 96 hr. Similar results, though delayed somewhat, were obtained after a single oral dose. Activity was accompanied by increases in weight and cholesterol content of livers. After multiple, daily, oral doses, liver weights, total lipids, and cholesterol contents were reduced. Hypobetalipopreteinmeic activity was enhanced by prolonged treatments as demonstrated by analyses of serum obtained weekly throughout 7 wk."}
{"id": "PMID:189154", "title": "An overview of the biochemical pharmacology of probucol.", "content": "Probucol was effective in lowering serum total cholesterol in mice at dietary livels as low as 0.0075%. It was also effective after a single 100 mg/kg I.V. dose in mice. The incorporation of acetate-(14)C into liver lipids of rats and mice was not significantly affected by probucol, although the results, especially in mice, make it impossible to rule out such an effect. Cholesterol absorption was estimated in rats using a dual isotope technique. The observed reductions were not statistically significant. Several liver enzyme activities were determined after probucol treatment in rats, and a significant elevation (32%) was observed in only one, glutamic dehydrogenase. Serum cholesterol was lowered markedly in cholesterol-fed cynomolgus monkeys by probucol. There was no effect on the excretion of neutral steroids and the observed increase in fecal bile acids after drug treatment could not be confirmed statistically.", "contents": "An overview of the biochemical pharmacology of probucol. Probucol was effective in lowering serum total cholesterol in mice at dietary livels as low as 0.0075%. It was also effective after a single 100 mg/kg I.V. dose in mice. The incorporation of acetate-(14)C into liver lipids of rats and mice was not significantly affected by probucol, although the results, especially in mice, make it impossible to rule out such an effect. Cholesterol absorption was estimated in rats using a dual isotope technique. The observed reductions were not statistically significant. Several liver enzyme activities were determined after probucol treatment in rats, and a significant elevation (32%) was observed in only one, glutamic dehydrogenase. Serum cholesterol was lowered markedly in cholesterol-fed cynomolgus monkeys by probucol. There was no effect on the excretion of neutral steroids and the observed increase in fecal bile acids after drug treatment could not be confirmed statistically."}
{"id": "PMID:189155", "title": "Regulation of fatty acid biosynthesis in Ehrlich cells by ascites tumor plasma lipoproteins.", "content": "Fatty acid biosynthesis in Ehrlich cells in vitro was reduced when very low density lipoproteins (VLDL) isolated from the ascites tumor plasma were added to the incubation medium. The degree of inhibition was dependent on the VLDL concentration. At the VLDL concentrations usually present in the ascites plasma, there was a 30% decrease in biosynthesis as measured by (3)H(2)O incorporation into fatty acids. Analysis of the labeled fatty acids by gas liquid chromatography indicated that this decrease was due to a reduction in fatty acid de novo biosynthesis and that chain elongation actually was increased when VLDL were present. Although ascites plasma low- and high density lipoproteins also produced a concentration-dependent inhibition of fatty acid biosynthesis, their effects were much smaller than those of the VLDL. Studies employing VLDL and radioactive free fatty acids indicated that the cells took up utlilzed fatty acids derived from these lipoproteins. When VLDL were present, labeled free fatty acid incorporation into cell phospholipids, cholesteryl esters, and CO(2) decreased, whereas its incorporation into the cell free fatty acid pool increased. By contrast, the cells incorporated only very small amounts of fatty acid from either low- or high density lipoproteins. This suggests that the VLDL exert their inhibitory effect on fatty acid synthesis by supplying exogenous fatty acids to the cells.", "contents": "Regulation of fatty acid biosynthesis in Ehrlich cells by ascites tumor plasma lipoproteins. Fatty acid biosynthesis in Ehrlich cells in vitro was reduced when very low density lipoproteins (VLDL) isolated from the ascites tumor plasma were added to the incubation medium. The degree of inhibition was dependent on the VLDL concentration. At the VLDL concentrations usually present in the ascites plasma, there was a 30% decrease in biosynthesis as measured by (3)H(2)O incorporation into fatty acids. Analysis of the labeled fatty acids by gas liquid chromatography indicated that this decrease was due to a reduction in fatty acid de novo biosynthesis and that chain elongation actually was increased when VLDL were present. Although ascites plasma low- and high density lipoproteins also produced a concentration-dependent inhibition of fatty acid biosynthesis, their effects were much smaller than those of the VLDL. Studies employing VLDL and radioactive free fatty acids indicated that the cells took up utlilzed fatty acids derived from these lipoproteins. When VLDL were present, labeled free fatty acid incorporation into cell phospholipids, cholesteryl esters, and CO(2) decreased, whereas its incorporation into the cell free fatty acid pool increased. By contrast, the cells incorporated only very small amounts of fatty acid from either low- or high density lipoproteins. This suggests that the VLDL exert their inhibitory effect on fatty acid synthesis by supplying exogenous fatty acids to the cells."}
{"id": "PMID:189156", "title": "Serum lipoproteins as inhibitors of haemafflutination by rubella virus.", "content": "The role of serum lipoproteins as non-antibody-like inhibitors of haemagglutination for rubella virus was investigated. Dissociation of lipoproteins into their respective lipid and protein components significantly reduced their inhibitory titre. This reduction was more prominent with the protein component. When mixtures of pure lipids were tested for their haemagglutination inhibitory activities, no inhibition was observed. Sonication of the three major lipoprotein fractions significantly increased the inhibitory activities of low density lipoproteins (LDL) and very low density lipoproteins (VLDL) but not high density lipoproteins (HDL). Succinylation, acetylation, and methylation of the lipoproteins did not appear to affect their inhibitory titre. On the other hand, phospholipase A treatment significantly increased the inhibitory properties of all lipoproteins fractions. These results are discussed in terms of the possible mechanisms by which the lipoproteins interact with the rubella haemagglutinins.", "contents": "Serum lipoproteins as inhibitors of haemafflutination by rubella virus. The role of serum lipoproteins as non-antibody-like inhibitors of haemagglutination for rubella virus was investigated. Dissociation of lipoproteins into their respective lipid and protein components significantly reduced their inhibitory titre. This reduction was more prominent with the protein component. When mixtures of pure lipids were tested for their haemagglutination inhibitory activities, no inhibition was observed. Sonication of the three major lipoprotein fractions significantly increased the inhibitory activities of low density lipoproteins (LDL) and very low density lipoproteins (VLDL) but not high density lipoproteins (HDL). Succinylation, acetylation, and methylation of the lipoproteins did not appear to affect their inhibitory titre. On the other hand, phospholipase A treatment significantly increased the inhibitory properties of all lipoproteins fractions. These results are discussed in terms of the possible mechanisms by which the lipoproteins interact with the rubella haemagglutinins."}
{"id": "PMID:189158", "title": "Turnover of apolipoprotein-B in two subjects with familial hypobetalipoproteinemia.", "content": "The metabolism of the apoprotein of low-density apoliporprotein-B was studied in a father and son with familial hypobetalipoproteinemia. The synthetic rate of apolipoprotein-B was below the normal range in both subjects, while the fractional removal rate was normal. It is concluded that the subnormal concentration of low-density lipoprotein (LDL) inthese two subjects is due to a low synthetic rate. The synthetic rate of apolipoprotein-B of very low-density lipoprotein (BLDL-apoB) measured in the father was subnormal. The fraction of the VLDL-apoB pool which was oncverted into LDL-apoB was within the normal range. It is suggested that a low synthetic rate of VLDL may underlie the disorder.", "contents": "Turnover of apolipoprotein-B in two subjects with familial hypobetalipoproteinemia. The metabolism of the apoprotein of low-density apoliporprotein-B was studied in a father and son with familial hypobetalipoproteinemia. The synthetic rate of apolipoprotein-B was below the normal range in both subjects, while the fractional removal rate was normal. It is concluded that the subnormal concentration of low-density lipoprotein (LDL) inthese two subjects is due to a low synthetic rate. The synthetic rate of apolipoprotein-B of very low-density lipoprotein (BLDL-apoB) measured in the father was subnormal. The fraction of the VLDL-apoB pool which was oncverted into LDL-apoB was within the normal range. It is suggested that a low synthetic rate of VLDL may underlie the disorder."}
{"id": "PMID:189159", "title": "Inheritance of type-III hyperlipoproteinemia. Lipoprotein patterns in first-degree relatives.", "content": "The lipoprotein (LP) patterns were studied in the families of 19 index cases with type-III hyperlipoproteinemia (HLP). Seventy adult first-degree relatives (93% ascertainment) to the 19 probands were analyzed. The diagnosis of HLP type III among the first-degree relatives was based on three criteria, all of which had to be fulfilled to make the diagnosis: (1) presence of a slow-moving band in very-low-density LP (VLDL) on agarose gel electrophoresis migrating in beta or close to beta position; (2) A cholesterol/triglyceride ratio (mg/100 ml: mmoles/liter) in VLDL greater than 29.0; and (3) A \"III-index\" [cholesterol/triglycerides in VLDL x 10 divided by cholesterol/triglycerides in low-density LP (LDL)] greater than 1.30. When defined according to these criteria there was a marked over-representation of HLP type III among the relatives (27%). There was also an increased frequency of hypertriglyceridemia (28% against expected 15%), mainly because of a high prevalence of HLP type IV (24%). On agarose gel electrophoresis a \"late pre-beta\" band, probably indicative of an increased amount of intermediary LP particles, was frequently present (47%) among relatives not classified as HLP type III. Type-III patients with hypertriglyceridemia were characterized by a significantly higher body weight than those with normotriglyceridemic type III. However, there was no qualitative difference in the composition of the lipoproteins in normotriglyceridemic and hypertriglyceridemic type-III patients. A genetic analysis of the LP patterns within the families showed several examples of vertical transmission of HLP type III. There was no sex linkage. Six of thirteen analyzed parents showed LP patterns classified as HLP type III. Another two parents were most probably carriers of the gene. Of the siblings to the probands, 23% showed a type-III pattern and another four (7%) showed LP patterns very similar to type III, fulfilling two of three criteria for HLP type III. The data support the concept that HLP type III is inherited as an autosomal dominant gene. It was indicated that HLP type IV with a late pre-beta band in VLDL may represent another expression of the gene for HLP type III. It is suggested that HLP type III may be a pathogenetically heterogenous group of lipid disorders. A separation of type III into two subgroups with low or normal and high LDL cholesterol concentration, respectively, may facilitate the understanding of the inheritance of type III as well as of the pathogenesis behind this LP abnormality.", "contents": "Inheritance of type-III hyperlipoproteinemia. Lipoprotein patterns in first-degree relatives. The lipoprotein (LP) patterns were studied in the families of 19 index cases with type-III hyperlipoproteinemia (HLP). Seventy adult first-degree relatives (93% ascertainment) to the 19 probands were analyzed. The diagnosis of HLP type III among the first-degree relatives was based on three criteria, all of which had to be fulfilled to make the diagnosis: (1) presence of a slow-moving band in very-low-density LP (VLDL) on agarose gel electrophoresis migrating in beta or close to beta position; (2) A cholesterol/triglyceride ratio (mg/100 ml: mmoles/liter) in VLDL greater than 29.0; and (3) A \"III-index\" [cholesterol/triglycerides in VLDL x 10 divided by cholesterol/triglycerides in low-density LP (LDL)] greater than 1.30. When defined according to these criteria there was a marked over-representation of HLP type III among the relatives (27%). There was also an increased frequency of hypertriglyceridemia (28% against expected 15%), mainly because of a high prevalence of HLP type IV (24%). On agarose gel electrophoresis a \"late pre-beta\" band, probably indicative of an increased amount of intermediary LP particles, was frequently present (47%) among relatives not classified as HLP type III. Type-III patients with hypertriglyceridemia were characterized by a significantly higher body weight than those with normotriglyceridemic type III. However, there was no qualitative difference in the composition of the lipoproteins in normotriglyceridemic and hypertriglyceridemic type-III patients. A genetic analysis of the LP patterns within the families showed several examples of vertical transmission of HLP type III. There was no sex linkage. Six of thirteen analyzed parents showed LP patterns classified as HLP type III. Another two parents were most probably carriers of the gene. Of the siblings to the probands, 23% showed a type-III pattern and another four (7%) showed LP patterns very similar to type III, fulfilling two of three criteria for HLP type III. The data support the concept that HLP type III is inherited as an autosomal dominant gene. It was indicated that HLP type IV with a late pre-beta band in VLDL may represent another expression of the gene for HLP type III. It is suggested that HLP type III may be a pathogenetically heterogenous group of lipid disorders. A separation of type III into two subgroups with low or normal and high LDL cholesterol concentration, respectively, may facilitate the understanding of the inheritance of type III as well as of the pathogenesis behind this LP abnormality."}
{"id": "PMID:189160", "title": "Effect of saline on the releasability of alkaline phosphatase from cells of Serratia marcescens.", "content": "The effect of 0.9% sodium chloride solution on the release of alkaline phosphatases from cells of four strains of Serratia marcescens was studied. Saline had a greater action in the releasability of the enzyme on cells of the polymyxin B sensitive strains than those of the polymyxin B resistant strains. SDS-polyacrylamide gel electrophoresis of the released materials showed the presence of proteins and lipopolysaccharide components of the outer membrane as well as enzyme activity in all four strains. Cells from strains harvested under higher temperatures contained more releasable activity in the salin wash fraction than those harvested under refrigerated condition. Active components with molecular weights of 190,000 and 110,000 daltons were either absent or present to a lesser degree in the extracts released by the polymyxin B treatment of the washed cells. However, active components not released by saline were found in the polymyxin B extracts. Contrary to other reports, results of this study clearly showed the ubiquitous nature of alkaline phosphatase in S. marcescens. It appears that their releasability is related to the polymyxin B susceptibility as well as the instability of the outer membrane of the cell envelope.", "contents": "Effect of saline on the releasability of alkaline phosphatase from cells of Serratia marcescens. The effect of 0.9% sodium chloride solution on the release of alkaline phosphatases from cells of four strains of Serratia marcescens was studied. Saline had a greater action in the releasability of the enzyme on cells of the polymyxin B sensitive strains than those of the polymyxin B resistant strains. SDS-polyacrylamide gel electrophoresis of the released materials showed the presence of proteins and lipopolysaccharide components of the outer membrane as well as enzyme activity in all four strains. Cells from strains harvested under higher temperatures contained more releasable activity in the salin wash fraction than those harvested under refrigerated condition. Active components with molecular weights of 190,000 and 110,000 daltons were either absent or present to a lesser degree in the extracts released by the polymyxin B treatment of the washed cells. However, active components not released by saline were found in the polymyxin B extracts. Contrary to other reports, results of this study clearly showed the ubiquitous nature of alkaline phosphatase in S. marcescens. It appears that their releasability is related to the polymyxin B susceptibility as well as the instability of the outer membrane of the cell envelope."}
{"id": "PMID:189161", "title": "Comparative release of alkaline phosphatases from Serratia marcescens by osmotic shock and polymyxin B treatment.", "content": "The comparative release of periplasmic enzymes and proteins from two strains of Serratia marcescens by osmotic shock and polymyxin B treatment was studied. There were significant qualitative and quantitative differences in the materials released by these two techniques. The osmotic shock procedure released a higher level of alkaline phosphatase activity and a greater number of protein components than the polymyxin B treatment. The molecular weights of the active components released by the two techniques were shown to be 190,000 +/- 10,000 (A'), 140,000 +/- 10,000 (A) and 110,000 +/- 10,000 (B) daltons. Components released by polymyxin B were also released by osmotic shock. However, the reverse was not true. Component B in the osmotic shock fluids was by far the most active. The differences in the release mechanisms of the two techniques were discussed. It is suggested that polymyxin B treatment is the method of choice because of its selectiveness and mildness, despite the rather low level of activity of alkaline phosphatase released.", "contents": "Comparative release of alkaline phosphatases from Serratia marcescens by osmotic shock and polymyxin B treatment. The comparative release of periplasmic enzymes and proteins from two strains of Serratia marcescens by osmotic shock and polymyxin B treatment was studied. There were significant qualitative and quantitative differences in the materials released by these two techniques. The osmotic shock procedure released a higher level of alkaline phosphatase activity and a greater number of protein components than the polymyxin B treatment. The molecular weights of the active components released by the two techniques were shown to be 190,000 +/- 10,000 (A'), 140,000 +/- 10,000 (A) and 110,000 +/- 10,000 (B) daltons. Components released by polymyxin B were also released by osmotic shock. However, the reverse was not true. Component B in the osmotic shock fluids was by far the most active. The differences in the release mechanisms of the two techniques were discussed. It is suggested that polymyxin B treatment is the method of choice because of its selectiveness and mildness, despite the rather low level of activity of alkaline phosphatase released."}
{"id": "PMID:189162", "title": "Radiolabelling of Bordetella pertussis envelope proteins by the 125 I-lactoperoxidase method.", "content": "Bordetella pertussis strain number 18334 was grown in media which yielded cells with either a normal complement of surface antigens (X-model), or cells which were phenotypically altered (C-model). Neither X- nor C-mode bacteria incorporated more than traces of radioactivity when exposed to Na 125 I, lactoperoxidase and a source of H2O2 under conditions which gave substantial labelling of BSA and other soluble proteins. In contrast, envelope preparations were readily labelled. Analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed that several polypeptides had incorporated 125 I but not in amounts proportional to their abundance in the envelopes. Envelopes from C-mode cells gave a labelling pattern similar to those of X-mode except in one region. Control experiments suggested that the failure of intact cells to become labelled may be due to bacterial inhibition of the reagents.", "contents": "Radiolabelling of Bordetella pertussis envelope proteins by the 125 I-lactoperoxidase method. Bordetella pertussis strain number 18334 was grown in media which yielded cells with either a normal complement of surface antigens (X-model), or cells which were phenotypically altered (C-model). Neither X- nor C-mode bacteria incorporated more than traces of radioactivity when exposed to Na 125 I, lactoperoxidase and a source of H2O2 under conditions which gave substantial labelling of BSA and other soluble proteins. In contrast, envelope preparations were readily labelled. Analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed that several polypeptides had incorporated 125 I but not in amounts proportional to their abundance in the envelopes. Envelopes from C-mode cells gave a labelling pattern similar to those of X-mode except in one region. Control experiments suggested that the failure of intact cells to become labelled may be due to bacterial inhibition of the reagents."}
{"id": "PMID:189163", "title": "[Comparative studies of mitochondria of Torulopsis candida growth on glucose and hexadecane].", "content": "The oxidative activity of mitochondria of Torulopsis candida was compared during its growth on glucose and hexadecane. No principal differences were found in the tricarboxylic acid cycle and the electron transport chain in the mitochondria of \"glucose\" and \"hexadecane\" cells (and in the rate of functioning too). The activity of enzyme systems involved in oxidation of higher alcohols, aldehydes and higher fatty acids was higher in the mitochondria of the \"hexadecane\" cells as compared to the \"glucose\" cells; oxidation of aldehydes, contrary to oxidation of aldehydes, contrary to oxidation of alcohols, was found to be susceptible to inhibitors of the respiration chain and phosphorylation. The rate of oxidation of exogenous NADH is much lower and the oxidative activity towards NADPH is practically absent in the mitochondria of the \"hexadecane\" cells as compared to the mitochondria of the \"glucose\" cells.", "contents": "[Comparative studies of mitochondria of Torulopsis candida growth on glucose and hexadecane]. The oxidative activity of mitochondria of Torulopsis candida was compared during its growth on glucose and hexadecane. No principal differences were found in the tricarboxylic acid cycle and the electron transport chain in the mitochondria of \"glucose\" and \"hexadecane\" cells (and in the rate of functioning too). The activity of enzyme systems involved in oxidation of higher alcohols, aldehydes and higher fatty acids was higher in the mitochondria of the \"hexadecane\" cells as compared to the \"glucose\" cells; oxidation of aldehydes, contrary to oxidation of aldehydes, contrary to oxidation of alcohols, was found to be susceptible to inhibitors of the respiration chain and phosphorylation. The rate of oxidation of exogenous NADH is much lower and the oxidative activity towards NADPH is practically absent in the mitochondria of the \"hexadecane\" cells as compared to the mitochondria of the \"glucose\" cells."}
{"id": "PMID:189169", "title": "[Chances in the serum lipid values after conversion to a \"reasonable\" diet (author's transl)].", "content": "Six to ten days after conversion from usual alimentary habits to a so-called \"reasonable\" regimen, the serum concentrations of different lipid fractions were examined under standardized conditions, in a total of 325 in-patients, who had not been pre-treated, and 268 of whom showed - after diverse examinations - a hyperlipoproteinaemia; the other 57 patients had normal lipid values. This diet food is vitamin-rich, poor in calories, protein-rich with a 20 per cent to 25 per cent part of calories, poor in carbohydrates (maximum 120 g/day), and extensively renouncing monomeric and dimeric carbohydrates; furthermore, it contains a percentage of 40 to 45 calories of lipids with a standardized part of multiple-unsaturated fatty acids. During the period of observation, there was in none of the patients an alteration of the body-weight exceeding 1 kg. During the period of the regimen, the following highly significant decreases - without any medicamentous measures - were stated with regard to the serum concentrations: Total cholesterol (average) 9.9 per cent, triglycerides (average) 23.1 per cent, beta-cholesterol (average) 17.6 per cent, and phosphatides (average) 14.2 per cent - all percentages being in relation to the reference values. A hyperproteinaemia (type IIa/Fredrickson) disappeared in 14 out of 18 cases, a hyperlipoproteinaemia (type IIb) in 14 out of 44 cases, and the same happened with this disease type IV in 114 out of 206 cases. A change of type was stated 16 times.", "contents": "[Chances in the serum lipid values after conversion to a \"reasonable\" diet (author's transl)]. Six to ten days after conversion from usual alimentary habits to a so-called \"reasonable\" regimen, the serum concentrations of different lipid fractions were examined under standardized conditions, in a total of 325 in-patients, who had not been pre-treated, and 268 of whom showed - after diverse examinations - a hyperlipoproteinaemia; the other 57 patients had normal lipid values. This diet food is vitamin-rich, poor in calories, protein-rich with a 20 per cent to 25 per cent part of calories, poor in carbohydrates (maximum 120 g/day), and extensively renouncing monomeric and dimeric carbohydrates; furthermore, it contains a percentage of 40 to 45 calories of lipids with a standardized part of multiple-unsaturated fatty acids. During the period of observation, there was in none of the patients an alteration of the body-weight exceeding 1 kg. During the period of the regimen, the following highly significant decreases - without any medicamentous measures - were stated with regard to the serum concentrations: Total cholesterol (average) 9.9 per cent, triglycerides (average) 23.1 per cent, beta-cholesterol (average) 17.6 per cent, and phosphatides (average) 14.2 per cent - all percentages being in relation to the reference values. A hyperproteinaemia (type IIa/Fredrickson) disappeared in 14 out of 18 cases, a hyperlipoproteinaemia (type IIb) in 14 out of 44 cases, and the same happened with this disease type IV in 114 out of 206 cases. A change of type was stated 16 times."}
{"id": "PMID:189164", "title": "[Various physiological aspects of Serratia marcescens pigmented strains and their pigmentless variants with an elevated nuclease activity].", "content": "Some aspects of physiology of Serratia marcescens pigmentless variants with elevated nuclease activity were studied. The variants are characterized by a higher respiration rate when glucose, glycerol, inositol or maltose are used as an energy substrate, a higher respiration quotient, a lower growth rate, a lower economic coefficient, and a lower thermogenesis. The growth of Serratia marcescens pigmentless strains is presumed to be unbalanced.", "contents": "[Various physiological aspects of Serratia marcescens pigmented strains and their pigmentless variants with an elevated nuclease activity]. Some aspects of physiology of Serratia marcescens pigmentless variants with elevated nuclease activity were studied. The variants are characterized by a higher respiration rate when glucose, glycerol, inositol or maltose are used as an energy substrate, a higher respiration quotient, a lower growth rate, a lower economic coefficient, and a lower thermogenesis. The growth of Serratia marcescens pigmentless strains is presumed to be unbalanced."}
{"id": "PMID:189170", "title": "[Errors in practising a so-called \"reasonable\" regimen (author's transl)].", "content": "The significant decrease of the serum concentrations of total cholesterol, triglycerides, phosphatides, beta-cholesterol, and beta-lipoproteins, which usually is observed after conversion from normal eating habits to a \"reasonable\" diet, is prevented by supplementary and unverifiable consumption of confectionery and/or by alcohol abuse in irregular intervals. The so-called \"reasonable\" regimen is a high-fat and protein-rich diet food containing more than 50 per cent of multiple-unsaturated fatty acid in the fat supply. The fact that the average serum concentrations of the divers lipid fractions within the entire group of the 30 patients examined (patients who - admittedly - were practising a luxury form of consumption) showed merely insignificant fluctuations, is in no way a justification for the conclusion that a \"reasonable\" diet will at any time ostensively represent a protection against the effect of luxury consumption on the serum lipids.", "contents": "[Errors in practising a so-called \"reasonable\" regimen (author's transl)]. The significant decrease of the serum concentrations of total cholesterol, triglycerides, phosphatides, beta-cholesterol, and beta-lipoproteins, which usually is observed after conversion from normal eating habits to a \"reasonable\" diet, is prevented by supplementary and unverifiable consumption of confectionery and/or by alcohol abuse in irregular intervals. The so-called \"reasonable\" regimen is a high-fat and protein-rich diet food containing more than 50 per cent of multiple-unsaturated fatty acid in the fat supply. The fact that the average serum concentrations of the divers lipid fractions within the entire group of the 30 patients examined (patients who - admittedly - were practising a luxury form of consumption) showed merely insignificant fluctuations, is in no way a justification for the conclusion that a \"reasonable\" diet will at any time ostensively represent a protection against the effect of luxury consumption on the serum lipids."}
{"id": "PMID:189165", "title": "[Effect of growth conditions on substrate phosphorylation during sulfite oxidation in Thiocapsa roseopersicina].", "content": "Cell extracts of Thiocapsa roseopersicina, strains BBS and SL, grown in the light under anaerobic conditions and in the dark under aerobic conditions on a medium containing thiosulphate produce ATP during oxidation of sulphite in the presence of AMP cytochrome c and inorganic phosphate. The uncoupling agent (m-chlorocarbonylcyanidephenylhydrazone) has no effect on the rate of ATP production, this being an evidence of substrate phosphorylation. The rate of ATP synthesis is higher in extracts of the cells grown in the dark under autotrophic conditions than in extracts of the cells cultivated in the light under anaerobic conditions or in the dark in the presence of thiosulphate and glucose.", "contents": "[Effect of growth conditions on substrate phosphorylation during sulfite oxidation in Thiocapsa roseopersicina]. Cell extracts of Thiocapsa roseopersicina, strains BBS and SL, grown in the light under anaerobic conditions and in the dark under aerobic conditions on a medium containing thiosulphate produce ATP during oxidation of sulphite in the presence of AMP cytochrome c and inorganic phosphate. The uncoupling agent (m-chlorocarbonylcyanidephenylhydrazone) has no effect on the rate of ATP production, this being an evidence of substrate phosphorylation. The rate of ATP synthesis is higher in extracts of the cells grown in the dark under autotrophic conditions than in extracts of the cells cultivated in the light under anaerobic conditions or in the dark in the presence of thiosulphate and glucose."}
{"id": "PMID:189166", "title": "[Flavinogenesis in methylotrophic yeasts].", "content": "Methylotrophic yeasts Candida boidinii and Hansenula polymorpha requiring thiamine and biotin accumulate more flavins in the cells during growth on media containing methanol than during oxidation of ethanol and glucose, at the account of increased production of FAD whose percentage in the total flavin content of the cell rises sharply. The level of flavin production depends on growth conditions: the intracellular content of flavins and FAD during utilization of methanol by the yeast cells is higher under conditions of continuous cultivation than in periodic cultures. The content of NAD, another coenzyme of the respiration chain, in the cells during their growth on media containing methanol almost does not differ from its concentration in the cells cultivated on media containing glucose and ethanol. Elevated production of flavins and FAD by the yeast cells on media containing methanol may be caused by an increased requirement in FAD and its specific participation in the first stage of methanol oxidation.", "contents": "[Flavinogenesis in methylotrophic yeasts]. Methylotrophic yeasts Candida boidinii and Hansenula polymorpha requiring thiamine and biotin accumulate more flavins in the cells during growth on media containing methanol than during oxidation of ethanol and glucose, at the account of increased production of FAD whose percentage in the total flavin content of the cell rises sharply. The level of flavin production depends on growth conditions: the intracellular content of flavins and FAD during utilization of methanol by the yeast cells is higher under conditions of continuous cultivation than in periodic cultures. The content of NAD, another coenzyme of the respiration chain, in the cells during their growth on media containing methanol almost does not differ from its concentration in the cells cultivated on media containing glucose and ethanol. Elevated production of flavins and FAD by the yeast cells on media containing methanol may be caused by an increased requirement in FAD and its specific participation in the first stage of methanol oxidation."}
{"id": "PMID:189167", "title": "[Differentiation of Blakeslea trispora mycelium in relation to carotene production].", "content": "Carotene synthesis by Blakeslea trispora is accompanied by a decrease in the rate of the main metabolic processes (protein synthesis, respiration) and changes in the bioenergetic pool of the mycelium. Considerable changes occur at the same time in the cytology of the microscopic fungus: the cell wall of the culture containing considerable amounts of carotene consists of many layers and peculiar thickened regions; partitions are formed; the nuclei are in the stage of interphase; lipid inclusions are larger and their number is higher.", "contents": "[Differentiation of Blakeslea trispora mycelium in relation to carotene production]. Carotene synthesis by Blakeslea trispora is accompanied by a decrease in the rate of the main metabolic processes (protein synthesis, respiration) and changes in the bioenergetic pool of the mycelium. Considerable changes occur at the same time in the cytology of the microscopic fungus: the cell wall of the culture containing considerable amounts of carotene consists of many layers and peculiar thickened regions; partitions are formed; the nuclei are in the stage of interphase; lipid inclusions are larger and their number is higher."}
{"id": "PMID:189176", "title": "Genes involved in the regulation of the neutral phosphatase in Chlamydomonas reinhardi.", "content": "In Chlamydomonas reinhardi, mutations in either of two unlinked genes (PD2 and PD3) abolish the activity of the derepressible neutral phosphatase. The question arose whether these genes (or one of them) specify the structure of the enzyme or whether they have a regulatory function. Three mutants producing an active phosphatase at 25 degrees C but not at 35 degrees C were isolated and investigated. One of these mutants (PDts11) was allelic with PD2, another one (PDts12) was linked to PD3 and the third one (PDts13) was linked to PD2. PDts11 and PDts13 affected the formation of the neutral phosphatase only whereas PDts12 interfered with the formation of both neutral and alkaline phosphatases at 35 degrees C. The neutral phosphatase produced by the three mutants at low temperature was not more thermosensitive in vitro than the wild enzyme. Moreover, quite similar Km values were found in WT, PDts11 and PDts12 using naphthyl phosphate as a substrate. On the other hand, revertants of PD-2 and PD-3 were isolated: their neutral phosphatases could not be distinguished from the wild enzyme on the basis of their thermosensitivities and Km values for naphthyl phosphate. These results are consistent with the idea that PD2 and PD3 are regulatory genes. Other possible regulatory genes were revealed through PDts12 and PDts13 mutations.", "contents": "Genes involved in the regulation of the neutral phosphatase in Chlamydomonas reinhardi. In Chlamydomonas reinhardi, mutations in either of two unlinked genes (PD2 and PD3) abolish the activity of the derepressible neutral phosphatase. The question arose whether these genes (or one of them) specify the structure of the enzyme or whether they have a regulatory function. Three mutants producing an active phosphatase at 25 degrees C but not at 35 degrees C were isolated and investigated. One of these mutants (PDts11) was allelic with PD2, another one (PDts12) was linked to PD3 and the third one (PDts13) was linked to PD2. PDts11 and PDts13 affected the formation of the neutral phosphatase only whereas PDts12 interfered with the formation of both neutral and alkaline phosphatases at 35 degrees C. The neutral phosphatase produced by the three mutants at low temperature was not more thermosensitive in vitro than the wild enzyme. Moreover, quite similar Km values were found in WT, PDts11 and PDts12 using naphthyl phosphate as a substrate. On the other hand, revertants of PD-2 and PD-3 were isolated: their neutral phosphatases could not be distinguished from the wild enzyme on the basis of their thermosensitivities and Km values for naphthyl phosphate. These results are consistent with the idea that PD2 and PD3 are regulatory genes. Other possible regulatory genes were revealed through PDts12 and PDts13 mutations."}
{"id": "PMID:189177", "title": "Assembly of the mitochondrial membrane system. XIX. Genetic characterization of mit- mutants with deficiencies in cytochrome oxidase and coenzyme qh2-cytochrome c reductase.", "content": "Nineteen mutants of S. cerevisiae exhibiting a double deficiency in cytochrome oxidase and coenzyme QH2-cytochrome c reductase (also cytochrome b deficient) have been studied. The mutants have been crossed to a set of rho- tester strains with different segments of mitochondrial DNA. The mutants have also been crossed to mit- testers with defined genetic lesions. In addition, crosses were performed with a respiratory competent strain to ascertain whether mitotic and meiotic segregants could be isolated with only one of the two enzymatic deficiencies. The rho- testers allowed the doubly deficient mutants to be separated into two classes. Mutants in class 1 were not restored by any of the rho- testers and appeared to have separate mutations, one in cytochrome oxidase and the other in cytochrome b. Mutants in class 2 were restored by a set of rho- clones whose retained segments of mitochondrial DNA contained the cytochrome b but not the cytochrome oxidase loci. These appeared to behave as single hit mutations. Further studies, however, indicated that both class 1 and class 2 mutants carried separate mutations in two different loci. Mitotic and meiotic segregants with a single enzymatic deficiency could be isolated. In a number of strains, the mutations were mapped in known cytochrome oxidase and cytochrome b loci. The apparent discrepancy of the rho- tests for the class 2 mutants was shown to be probably due to a high unstability in one of the mutations. It has been concluded that all the doubly deficient strains carry two mutations in previously described cytochrome oxidase and cytochrome b loci. This conclusion argues against the existence of a single gene on mitochondrial DNA that controls the biosynthesis of the two respiratory enzymes.", "contents": "Assembly of the mitochondrial membrane system. XIX. Genetic characterization of mit- mutants with deficiencies in cytochrome oxidase and coenzyme qh2-cytochrome c reductase. Nineteen mutants of S. cerevisiae exhibiting a double deficiency in cytochrome oxidase and coenzyme QH2-cytochrome c reductase (also cytochrome b deficient) have been studied. The mutants have been crossed to a set of rho- tester strains with different segments of mitochondrial DNA. The mutants have also been crossed to mit- testers with defined genetic lesions. In addition, crosses were performed with a respiratory competent strain to ascertain whether mitotic and meiotic segregants could be isolated with only one of the two enzymatic deficiencies. The rho- testers allowed the doubly deficient mutants to be separated into two classes. Mutants in class 1 were not restored by any of the rho- testers and appeared to have separate mutations, one in cytochrome oxidase and the other in cytochrome b. Mutants in class 2 were restored by a set of rho- clones whose retained segments of mitochondrial DNA contained the cytochrome b but not the cytochrome oxidase loci. These appeared to behave as single hit mutations. Further studies, however, indicated that both class 1 and class 2 mutants carried separate mutations in two different loci. Mitotic and meiotic segregants with a single enzymatic deficiency could be isolated. In a number of strains, the mutations were mapped in known cytochrome oxidase and cytochrome b loci. The apparent discrepancy of the rho- tests for the class 2 mutants was shown to be probably due to a high unstability in one of the mutations. It has been concluded that all the doubly deficient strains carry two mutations in previously described cytochrome oxidase and cytochrome b loci. This conclusion argues against the existence of a single gene on mitochondrial DNA that controls the biosynthesis of the two respiratory enzymes."}
{"id": "PMID:189178", "title": "Mutagen sensitivity of Drosophila melanogaster. III. X-linked loci governing sensitivity to methyl methanesulfonate.", "content": "Twenty-eight X-linked, recessive mutations of Drosophila melanogaster conferring enhanced sensitivity to the monofunctional alkylating agent, methyl methanesulfonate, have been recoered and assigned to five complementation groups. These groups can be distinguished on the basis of map location and variations in the pattern of mutagen sensitivity. Allelism of members of one complementation group with the previously described meiotic mutant, mei-41, (Baker and Carpenter, 1972) as well as the frequent appearance of female infertility with mutagen sensitivity suggests associated defects in meiotic chromosome behavior or early embryogenesis. Examination of the mutagen sensitivity of double mutants has led to the formulation of a working model of DNA repair for this organism. Studies  of a similar nature (Boyd et al., 1976) have identified five additional X chromosome complementation groups, suggesting that the genome of Drosophila melanogaster may contain many loci involved with mutagen sensitivity. The continued isolation and characterization of conditional mutants of this type promises future insights into the mechanisms of DNA replication, DNA repair and recombination in this complex higher eucaryote.", "contents": "Mutagen sensitivity of Drosophila melanogaster. III. X-linked loci governing sensitivity to methyl methanesulfonate. Twenty-eight X-linked, recessive mutations of Drosophila melanogaster conferring enhanced sensitivity to the monofunctional alkylating agent, methyl methanesulfonate, have been recoered and assigned to five complementation groups. These groups can be distinguished on the basis of map location and variations in the pattern of mutagen sensitivity. Allelism of members of one complementation group with the previously described meiotic mutant, mei-41, (Baker and Carpenter, 1972) as well as the frequent appearance of female infertility with mutagen sensitivity suggests associated defects in meiotic chromosome behavior or early embryogenesis. Examination of the mutagen sensitivity of double mutants has led to the formulation of a working model of DNA repair for this organism. Studies  of a similar nature (Boyd et al., 1976) have identified five additional X chromosome complementation groups, suggesting that the genome of Drosophila melanogaster may contain many loci involved with mutagen sensitivity. The continued isolation and characterization of conditional mutants of this type promises future insights into the mechanisms of DNA replication, DNA repair and recombination in this complex higher eucaryote."}
{"id": "PMID:189179", "title": "Glutamine utilization in both the arginine-specific and pyrimidine-specific carbamoyl phosphate synthase enzymes of eurospora crassa.", "content": "As glutamine-dependent carbamoyl phasphate synthetase (CPS) activity in some organisms is composed of a glutaminase and an ammonium-dependent CPS, CPS- mutants in Neurospora crassa were examined for glutamine- and ammonium-dependent CPS activities. No evidence was found that the genetic location of these two functions were separable. This is discussed with reference to the close genetic proximity of the CPSpyr and aspartate carbamoyltransferase (ACT) structural gene (pyr-3) and the arg-2 gene which appears to specify a subunit responsible for glutamine utilisation in CPSarg.", "contents": "Glutamine utilization in both the arginine-specific and pyrimidine-specific carbamoyl phosphate synthase enzymes of eurospora crassa. As glutamine-dependent carbamoyl phasphate synthetase (CPS) activity in some organisms is composed of a glutaminase and an ammonium-dependent CPS, CPS- mutants in Neurospora crassa were examined for glutamine- and ammonium-dependent CPS activities. No evidence was found that the genetic location of these two functions were separable. This is discussed with reference to the close genetic proximity of the CPSpyr and aspartate carbamoyltransferase (ACT) structural gene (pyr-3) and the arg-2 gene which appears to specify a subunit responsible for glutamine utilisation in CPSarg."}
{"id": "PMID:189180", "title": "Synthesis of cytochrome c oxidase polypeptides in an Escherichia coli cell-free system directed by Saccharomyces cerevisiae mitochondrial DNA.", "content": "Using purified yeast mitochondrial DNA as a template for E. coli RNA polymerase (holoenzyme) complementary mitochondrial RNA has been synthesized in vitro. This RNA has been used to direct a low background E. coli S-30 protein-synthesizing system. The synthesis of mitochondrial polypeptides has been detected by using antiserum raised against purified cytochrome c oxidase holoenzyme and shown to be specific for this antigen. The antiserum-antigen complex was dissociated and subject to SDS-polyacrylamide gel electrophoresis and the presence of 3 polypeptides of 39, 31, and 26 X 10(3) daltons molecular weight demonstrated, which correspond to the subunits synthesized by mitochondria in whole cells which are inhibited with cycloheximide.", "contents": "Synthesis of cytochrome c oxidase polypeptides in an Escherichia coli cell-free system directed by Saccharomyces cerevisiae mitochondrial DNA. Using purified yeast mitochondrial DNA as a template for E. coli RNA polymerase (holoenzyme) complementary mitochondrial RNA has been synthesized in vitro. This RNA has been used to direct a low background E. coli S-30 protein-synthesizing system. The synthesis of mitochondrial polypeptides has been detected by using antiserum raised against purified cytochrome c oxidase holoenzyme and shown to be specific for this antigen. The antiserum-antigen complex was dissociated and subject to SDS-polyacrylamide gel electrophoresis and the presence of 3 polypeptides of 39, 31, and 26 X 10(3) daltons molecular weight demonstrated, which correspond to the subunits synthesized by mitochondria in whole cells which are inhibited with cycloheximide."}
{"id": "PMID:189184", "title": "The existence of triphosphorylated 5'-ends in virus-specific RNA isolated from SV-40 transformed cells.", "content": "The question about the nature of promoters in the transcriptional units containing SV-40 sequences in transformed cells was analyzed. It was found that the pulse-labeled RNA hybridizing to SV-40 DNA contains small but significant amounts of triphosphorylated 5'-ends detected as pppGp in alkaline hydrolyzates of this RNA. In another series of experiments the fragments of RNA containing triphosphorylated 5'-ends about 100 nucleotides in length have been isolated by hydroxyapatite chromatography. Some of them form hybrids with SV-40 DNA. The conclusion is drawn that at least some of SV-40 promoters are used for transcription initiation in SV-40 transformed cells.", "contents": "The existence of triphosphorylated 5'-ends in virus-specific RNA isolated from SV-40 transformed cells. The question about the nature of promoters in the transcriptional units containing SV-40 sequences in transformed cells was analyzed. It was found that the pulse-labeled RNA hybridizing to SV-40 DNA contains small but significant amounts of triphosphorylated 5'-ends detected as pppGp in alkaline hydrolyzates of this RNA. In another series of experiments the fragments of RNA containing triphosphorylated 5'-ends about 100 nucleotides in length have been isolated by hydroxyapatite chromatography. Some of them form hybrids with SV-40 DNA. The conclusion is drawn that at least some of SV-40 promoters are used for transcription initiation in SV-40 transformed cells."}
{"id": "PMID:189185", "title": "[Anesthesia for short or outpatient operations (author's transl)].", "content": "It was intended to find out for which operations and operative investigations ambulant anesthesia offered advantages, what conditions must be fulfilled and which methods of anesthesia are suitable. The question arose not only because of increasing hospital costs, but also because of personal advantages of the out-patient operation for the patients and their families and for other reasons. The importance of consultation with the anesthetist in which the ambulant patient is prepared is emphasized and from there communications to the participants and questions of postoperative safety are examined.", "contents": "[Anesthesia for short or outpatient operations (author's transl)]. It was intended to find out for which operations and operative investigations ambulant anesthesia offered advantages, what conditions must be fulfilled and which methods of anesthesia are suitable. The question arose not only because of increasing hospital costs, but also because of personal advantages of the out-patient operation for the patients and their families and for other reasons. The importance of consultation with the anesthetist in which the ambulant patient is prepared is emphasized and from there communications to the participants and questions of postoperative safety are examined."}
{"id": "PMID:189186", "title": "Dose response at low doses of X-irradiation and MMS on the induction of micronuclei in mouse erythroblasts.", "content": "The test of induced micronuclei in erythrocytes of mammalian bone marrow constitutes, because of its high experimental resolution power, a suitable method for the screening of induced chromosomal lesions at very low dosages of chemicals or irradiations. This test was used for a comparative investigation of the effect of low dose levels of X-irradiation and of the alkylating agent methyl methanesulphonate (MMS). The dose-effect curve of X-irradiation indicated a deviation from linearity at 10 rad, showing a significantly stronger effect than expected on extrapolation from the control to 100 rad. This deviation from linarity, however, only appeared at a low dose rate (18 R/min), whereas a linear dose-effect relation was indicated with a high dose rate (95 R/min). Experiments at 10 rad with different dose rates at two different current potentials suggested that this effect of the dose rate is more pronounced with soft than with hard X-irradiation. The induction of micronuclei with MMS follows a drastically different dose-effect curve as compared with X-irradiation. The relative efficiency of the treatment is lowest at low concentrations, presumably as a result of the efficient repair process at such dose levels. Simultaneous treatment with X-rays and MMS at low dose levels only resulted in an additive effect. This suggests that X-irradiation does not interfere with the repair process operating with MMS. The difference in the dose-effect relations of X-irradiation as compared with MMS may be brought back to the fact that X-rays, in contrast with MMS, produce double-strand breaks.", "contents": "Dose response at low doses of X-irradiation and MMS on the induction of micronuclei in mouse erythroblasts. The test of induced micronuclei in erythrocytes of mammalian bone marrow constitutes, because of its high experimental resolution power, a suitable method for the screening of induced chromosomal lesions at very low dosages of chemicals or irradiations. This test was used for a comparative investigation of the effect of low dose levels of X-irradiation and of the alkylating agent methyl methanesulphonate (MMS). The dose-effect curve of X-irradiation indicated a deviation from linearity at 10 rad, showing a significantly stronger effect than expected on extrapolation from the control to 100 rad. This deviation from linarity, however, only appeared at a low dose rate (18 R/min), whereas a linear dose-effect relation was indicated with a high dose rate (95 R/min). Experiments at 10 rad with different dose rates at two different current potentials suggested that this effect of the dose rate is more pronounced with soft than with hard X-irradiation. The induction of micronuclei with MMS follows a drastically different dose-effect curve as compared with X-irradiation. The relative efficiency of the treatment is lowest at low concentrations, presumably as a result of the efficient repair process at such dose levels. Simultaneous treatment with X-rays and MMS at low dose levels only resulted in an additive effect. This suggests that X-irradiation does not interfere with the repair process operating with MMS. The difference in the dose-effect relations of X-irradiation as compared with MMS may be brought back to the fact that X-rays, in contrast with MMS, produce double-strand breaks."}
{"id": "PMID:189187", "title": "Heritable translocation test and dominant-lethal assay in mice with methyl methanesulfonate.", "content": "A dominant-lethal test and a heritable translocation test were performed with methyl methanesulphonate (MMS) at 40 mg/kg by treating the sensitive periods of post-meiotic spermatogenesis i.e. spermatozoa and spermatids. In the dominant-lethal test 25 to 60% dominant-lethal mutations were obtained depending on the mating intervals. In the heritable translocation test 11% sterile and partially sterile F1 males were observed in 250 offspring of the MMS group. All of the 14 partially sterile and 6 of the 14 sterile F1 males were demonstrated to be translocation carriers. Fertility of the partial steriles was about 40% of normal fertility. The translocation frequencies in the primary spermatocytes of the partially sterile F1 males varied between 2 and 99%. Transmission of partial sterility and translocations was confirmed in the F2 generation. There were no partially sterile or sterile males among the 245 controls.", "contents": "Heritable translocation test and dominant-lethal assay in mice with methyl methanesulfonate. A dominant-lethal test and a heritable translocation test were performed with methyl methanesulphonate (MMS) at 40 mg/kg by treating the sensitive periods of post-meiotic spermatogenesis i.e. spermatozoa and spermatids. In the dominant-lethal test 25 to 60% dominant-lethal mutations were obtained depending on the mating intervals. In the heritable translocation test 11% sterile and partially sterile F1 males were observed in 250 offspring of the MMS group. All of the 14 partially sterile and 6 of the 14 sterile F1 males were demonstrated to be translocation carriers. Fertility of the partial steriles was about 40% of normal fertility. The translocation frequencies in the primary spermatocytes of the partially sterile F1 males varied between 2 and 99%. Transmission of partial sterility and translocations was confirmed in the F2 generation. There were no partially sterile or sterile males among the 245 controls."}
{"id": "PMID:189188", "title": "Familial hyperglucagonemia--an autosomal dominant disorder.", "content": "Basal immunoreactive glucagon was elevated in four of nine asymptomatic relatives of a patient with glucagonoma. Immunoreactive glucagon remained elevated throughout 22 to 25 hours of continuous observation. Glucagon responses to intravenous glucose and arginine or mixed meals (or both) were abnormal, whereas glucose and insulin responses were normal. Gel filtration of plasma revealed that over 85 per cent of the four relatives' immunoreactive glucagon had a molecular weight of greater than 9000 daltons whereas that of 70 per cent of the patients with glucagonoma had a molecular weight of 3500 daltons, with the remainder eluting in the area of 9000 daltons. Pancreatic angiograms and hepatic scintiscans were normal in all four relatives. The data suggest an autosomal dominant transmission of hyperglucagonemia in this family. Immunoreactive glucagon with a molecular weight of 3500 or 9000 daltons appears to be required for the development of the clinical glucagonoma syndrome.", "contents": "Familial hyperglucagonemia--an autosomal dominant disorder. Basal immunoreactive glucagon was elevated in four of nine asymptomatic relatives of a patient with glucagonoma. Immunoreactive glucagon remained elevated throughout 22 to 25 hours of continuous observation. Glucagon responses to intravenous glucose and arginine or mixed meals (or both) were abnormal, whereas glucose and insulin responses were normal. Gel filtration of plasma revealed that over 85 per cent of the four relatives' immunoreactive glucagon had a molecular weight of greater than 9000 daltons whereas that of 70 per cent of the patients with glucagonoma had a molecular weight of 3500 daltons, with the remainder eluting in the area of 9000 daltons. Pancreatic angiograms and hepatic scintiscans were normal in all four relatives. The data suggest an autosomal dominant transmission of hyperglucagonemia in this family. Immunoreactive glucagon with a molecular weight of 3500 or 9000 daltons appears to be required for the development of the clinical glucagonoma syndrome."}
{"id": "PMID:189194", "title": "Effects of growth temperature and caffeine on genetic responses of Candida albicans to ethyl methanesulfonate, nitrous acid and ultraviolet radiation.", "content": "Ultraviolet radiation is more effective than either ethyl methanesulfonate or nitrous acid in inducing reverse mutation from auxotrophy to prototrophy in C. albicans. The killing effect of each of the mutagens is greater for cells grown at 37 C than at 25 C after treatment; mutation frequencies are unaffected by post-treatment growth temperatures. Though caffeine depresses survival of mutagen treated cells at both 25 C or 37 C, its effect is more pronounced at 37 C. Caffeine has no effect on mutagenesis by nitrous acid or ethyl methanesulfonate; it depresses UV mutagenesis, but only at 37 C and at high UV dosages. These findings indicate that UV mutagenesis in C. albicans is mediated by a caffeine-sensitive, recombinational system for DNA repair analogous to those known to occur in other species of yeasts. The repair system of C. albicans is unique in being susceptible to caffeine only at high temperature and when the number of DNA lesions to be repaired is large. The caffeine-sensitive steps in repair critical to UV mutagenesis are not involved in fixing mutations induced by the chemical mutagens tested.", "contents": "Effects of growth temperature and caffeine on genetic responses of Candida albicans to ethyl methanesulfonate, nitrous acid and ultraviolet radiation. Ultraviolet radiation is more effective than either ethyl methanesulfonate or nitrous acid in inducing reverse mutation from auxotrophy to prototrophy in C. albicans. The killing effect of each of the mutagens is greater for cells grown at 37 C than at 25 C after treatment; mutation frequencies are unaffected by post-treatment growth temperatures. Though caffeine depresses survival of mutagen treated cells at both 25 C or 37 C, its effect is more pronounced at 37 C. Caffeine has no effect on mutagenesis by nitrous acid or ethyl methanesulfonate; it depresses UV mutagenesis, but only at 37 C and at high UV dosages. These findings indicate that UV mutagenesis in C. albicans is mediated by a caffeine-sensitive, recombinational system for DNA repair analogous to those known to occur in other species of yeasts. The repair system of C. albicans is unique in being susceptible to caffeine only at high temperature and when the number of DNA lesions to be repaired is large. The caffeine-sensitive steps in repair critical to UV mutagenesis are not involved in fixing mutations induced by the chemical mutagens tested."}
{"id": "PMID:189219", "title": "Inoculation experiment of Marek's disease vaccine contaminated with a reticuloendotheliosis virus.", "content": "Two-day-old chicks were inoculated with one or ten doses of Marek's disease (MD) vaccine originated from the herpesvirus of turkeys (HVT) and contaminated with a reticuloendotheliosis virus (REV). As a result, they presented such symptoms as abnormality in the vane of remiges, undergrowth, anemia, and leg paralysis. These symptoms were the same as those induced by the same vaccine among chicks in the field. Control chicks which had been placed in the same house as those inoculated with the vaccine exhibited no abnormal signs. A persistent infection with REV was noticed in the vaccine-inoculated group. A horizontal infection with REV was the highest in the control group, which was followed by the group inoculated with one dose and that inoculated with ten doses in the order listed. The antibody response of chicks to HVT and MD virus was also inhibited by REV.", "contents": "Inoculation experiment of Marek's disease vaccine contaminated with a reticuloendotheliosis virus. Two-day-old chicks were inoculated with one or ten doses of Marek's disease (MD) vaccine originated from the herpesvirus of turkeys (HVT) and contaminated with a reticuloendotheliosis virus (REV). As a result, they presented such symptoms as abnormality in the vane of remiges, undergrowth, anemia, and leg paralysis. These symptoms were the same as those induced by the same vaccine among chicks in the field. Control chicks which had been placed in the same house as those inoculated with the vaccine exhibited no abnormal signs. A persistent infection with REV was noticed in the vaccine-inoculated group. A horizontal infection with REV was the highest in the control group, which was followed by the group inoculated with one dose and that inoculated with ten doses in the order listed. The antibody response of chicks to HVT and MD virus was also inhibited by REV."}
{"id": "PMID:189220", "title": "Isolation of a reticuloendotheliosis virus from chickens inoculated with Marek's disease vaccine.", "content": "Over a period from spring to fall in 1974, a disease with delayed growth, anemia, abnormal feathers, and leg paralysis as main symptoms broke out in flocks of chickens inoculated with Marek's disease vaccine. A virus was isolated from affected birds in the field and the same lot of Marek's disease vaccine as inoculated into these birds. It had a common antigenicity to the T strain of reticuloendotheliosis virus (REV) and could not be discriminated from this strain on the basis of morphology or property. When chicks were inoculated with it, they presented essentially the same symptoms as the birds affected in the field. Since the disease was reproduced in this manner, it was presumed to have been caused by REV contained in the vaccine as contaminant. The virus persisted in the body for long time and also induced horizontal infection.", "contents": "Isolation of a reticuloendotheliosis virus from chickens inoculated with Marek's disease vaccine. Over a period from spring to fall in 1974, a disease with delayed growth, anemia, abnormal feathers, and leg paralysis as main symptoms broke out in flocks of chickens inoculated with Marek's disease vaccine. A virus was isolated from affected birds in the field and the same lot of Marek's disease vaccine as inoculated into these birds. It had a common antigenicity to the T strain of reticuloendotheliosis virus (REV) and could not be discriminated from this strain on the basis of morphology or property. When chicks were inoculated with it, they presented essentially the same symptoms as the birds affected in the field. Since the disease was reproduced in this manner, it was presumed to have been caused by REV contained in the vaccine as contaminant. The virus persisted in the body for long time and also induced horizontal infection."}
{"id": "PMID:189221", "title": "Typing foot-and-mouth disease virus by fluorescent antibody technique.", "content": "Typing of foot-and-mouth disease (FMD) virus was performed by the direct fluorescent antibody (FA) technique. Type-specific FA was prepared from the following two sorts of procedures: (1) FA against live virus (FA-live) was prepared from hyperimmune serum taken from guinea pigs having received live FMD virus. Then it was adsorbed with concentrated heterotype antigen. (2) FA against inactivated virus (FA-Inact) was prepared from antiserum taken from guinea pigs immunized with purified FMD virus inactivated with acetylethyleneimine. Seventeen strains of FMD virus (seven strains of type A, seven strains of type O, and three strains of thpe C) were used. Type-specific FMD virus antigen was detected distinctly from the monolayer of BHK cells infected with each type of virus and fixed in acetone, in spite of negative results obtained from the cells fixed in methyl alcohol. All the 17 strains were typed successfully by the implementation of these two FA methods.", "contents": "Typing foot-and-mouth disease virus by fluorescent antibody technique. Typing of foot-and-mouth disease (FMD) virus was performed by the direct fluorescent antibody (FA) technique. Type-specific FA was prepared from the following two sorts of procedures: (1) FA against live virus (FA-live) was prepared from hyperimmune serum taken from guinea pigs having received live FMD virus. Then it was adsorbed with concentrated heterotype antigen. (2) FA against inactivated virus (FA-Inact) was prepared from antiserum taken from guinea pigs immunized with purified FMD virus inactivated with acetylethyleneimine. Seventeen strains of FMD virus (seven strains of type A, seven strains of type O, and three strains of thpe C) were used. Type-specific FMD virus antigen was detected distinctly from the monolayer of BHK cells infected with each type of virus and fixed in acetone, in spite of negative results obtained from the cells fixed in methyl alcohol. All the 17 strains were typed successfully by the implementation of these two FA methods."}
{"id": "PMID:189222", "title": "Fine structure of epithelial cells of Lieberk\u00fchn's crypts in feline panleukopenia.", "content": "Electron microscopic observation was carried out on epithelial cells of Lieberk\u00fchn's crypts of cats naturally affected with feline panleukopenia. The most important change was the replication of feline panleukopenia. The most important change was the replication of feline panleukopenia virus in the nucleus with associated alterations in the lining epithelial cells of the crypts. In these cells in the early stage of infection, virus particles 20 nm in average diameter were found either singly or in small regularly arrayed clusters everywhere in the markedly swollen nucleus. In the course of infection, the nucleus of infected cells became rather atrophic with a marked margination of chromatin granules. Its major portion was occupied with masses of fine fibrillar substance. It was a \"viral matrix area\" in which appeared a large compact aggregate of virus particles showing a crystalline array. At the same time, the outer membrane of the nuclear envelope partially extended and disrupted. Membranous elements related to it in the cytoplasm were regularly distributed almost always with particles indistinguishable from the virus particles in the nucleus. From these results it was suggested that the major portion of the infected nucleus, or the site of viral replication, might correspond to the amphophilic intranuclear inclusion body revealed by light microscopy.", "contents": "Fine structure of epithelial cells of Lieberk\u00fchn's crypts in feline panleukopenia. Electron microscopic observation was carried out on epithelial cells of Lieberk\u00fchn's crypts of cats naturally affected with feline panleukopenia. The most important change was the replication of feline panleukopenia. The most important change was the replication of feline panleukopenia virus in the nucleus with associated alterations in the lining epithelial cells of the crypts. In these cells in the early stage of infection, virus particles 20 nm in average diameter were found either singly or in small regularly arrayed clusters everywhere in the markedly swollen nucleus. In the course of infection, the nucleus of infected cells became rather atrophic with a marked margination of chromatin granules. Its major portion was occupied with masses of fine fibrillar substance. It was a \"viral matrix area\" in which appeared a large compact aggregate of virus particles showing a crystalline array. At the same time, the outer membrane of the nuclear envelope partially extended and disrupted. Membranous elements related to it in the cytoplasm were regularly distributed almost always with particles indistinguishable from the virus particles in the nucleus. From these results it was suggested that the major portion of the infected nucleus, or the site of viral replication, might correspond to the amphophilic intranuclear inclusion body revealed by light microscopy."}
{"id": "PMID:189224", "title": "Adrenal cortex adenylate cyclase. In vitro acitivity of ACTH fragments and analogues.", "content": "The ability of ACTH fragments and of an ACTH analogue [9-tryptophan(o-nitrophenylsulfenyl)] corticotropin-(1-24)-tetracosapeptide[Trp-(Nps)9 ACTH1-24] to stimulate adenylate cyclase in bovine adrenal cortex membranes and a crude membrane fraction from rat adrenals has been determined. Partial agonists like Trp (Nps)9 ACTH1-24 displayed intrinsic activity in the rat adrenal preparation only if tested in the presence of 5'-guanylylimidodiphosphate [Gpp(NH)p]. On the other hand, no addition of Gpp(NH)p was necessary to demonstrate intrinsic activity of Trp(Nps)9 ACTH1-24 for bovine adrenal cortex adenylate cyclase. A large decrease (15-fold) of the apparent Km values for ACTH1-24, ACTH1-23 and ACTH1-17 was observed with the rat adrenal preparation when Gpp(NH)p was added. The shift in apparent Km values for ACTH1-24 and ACTH1-23 for the bovine adrenal cortex adenylate cyclase system was small or insignificant when Gpp(NH)p was added. The observations suggest that the hormone receptor facilitates the action of guanylnucleotide sites in the membrane. When guanylnucleotide sites are occupied by Gpp(NH)p even weak interactions of the hormone receptor with e.g. partial agonists are propagated to the catalytic subunits of the adenylate cyclase complex resulting in enhanced activity. The differences in adenylate cyclase activation with hormone fragments or analogues and different target tissues may rather reflect the state of the coupling process involving guanylnucleotide binding sites of the isolated membrane fraction than differences in the receptor itself.", "contents": "Adrenal cortex adenylate cyclase. In vitro acitivity of ACTH fragments and analogues. The ability of ACTH fragments and of an ACTH analogue [9-tryptophan(o-nitrophenylsulfenyl)] corticotropin-(1-24)-tetracosapeptide[Trp-(Nps)9 ACTH1-24] to stimulate adenylate cyclase in bovine adrenal cortex membranes and a crude membrane fraction from rat adrenals has been determined. Partial agonists like Trp (Nps)9 ACTH1-24 displayed intrinsic activity in the rat adrenal preparation only if tested in the presence of 5'-guanylylimidodiphosphate [Gpp(NH)p]. On the other hand, no addition of Gpp(NH)p was necessary to demonstrate intrinsic activity of Trp(Nps)9 ACTH1-24 for bovine adrenal cortex adenylate cyclase. A large decrease (15-fold) of the apparent Km values for ACTH1-24, ACTH1-23 and ACTH1-17 was observed with the rat adrenal preparation when Gpp(NH)p was added. The shift in apparent Km values for ACTH1-24 and ACTH1-23 for the bovine adrenal cortex adenylate cyclase system was small or insignificant when Gpp(NH)p was added. The observations suggest that the hormone receptor facilitates the action of guanylnucleotide sites in the membrane. When guanylnucleotide sites are occupied by Gpp(NH)p even weak interactions of the hormone receptor with e.g. partial agonists are propagated to the catalytic subunits of the adenylate cyclase complex resulting in enhanced activity. The differences in adenylate cyclase activation with hormone fragments or analogues and different target tissues may rather reflect the state of the coupling process involving guanylnucleotide binding sites of the isolated membrane fraction than differences in the receptor itself."}
{"id": "PMID:189225", "title": "Studies on the possible contribution of a peripheral presynaptic action of clonidine and dopamine to their vascular effects under in vivo conditions.", "content": "The functional consequences of drug-induced stimulation under in vivo conditions of alpha-adrenoceptors and dopamine receptors at vascular adrenergic nerve endings (presynaptic receptors) was studied in the autoperfused hindquarters or hindlegs of cats anaesthetized with urethane. The changes in perfusion pressure in response to electrical stimulation of the lumbar sympathetic chain were taken as a measure of noradrenaline release from the vascular adrenergic nerves. Presynaptic inhibitory alpha-adrenoceptors and dopamine receptors were activated by clonidine and dopamine, respectively. According to in vitro experiments these two drugs are more potent stimulants of peripheral presynaptic than postsynaptic receptors. The lowest frequency of stimulation of the lumbar sympathetic chain which yielded a reproducible pressor response was 4 HZ for the autoperfused hindquarters and 1 HZ for the hindlegs; Clonidine was tested over a wide dose range (1-100 mug/kg i;v). A reduction of the stimulation-induced pressor response in the autoperfused hindquarters or hindlegs was observed only after the rather high dose of 100 mug/kg of clonidine. The inhibition was marked at low frequencies of stimulation (1-4 HZ) and weak or absent at high frequencies (16 and 32 HZ). The dose of clonidine (100 mug/kg) which proved to be effective at presynaptic receptors produced a transient increase in blood pressure and in perfusion pressure of the hindquarters and hindlegs and virtually abolished spontaneous sympathetic nervous activity. In spinal cats, the clonidine-induced increases in blood pressure and perfusion pressure were very pronounced and of rather long duration. Thus, under in vivo conditions clonidine showed no selectivity for presynaptic alpha-adrenoceptors in a blood-perfused vascular bed, and its presynaptic action was negligible as compared to its powerful central sympatho-inhibitory effect. Dopamine was constantly infused into the auto-perfused hindquarters or hindlegs at increasing rates until a vasoconstriction due to stimulation of vascular (postsynaptic) alpha-adrenoceptors occurred. The monoamine did not inhibit the stimulation-induced increases in perfusion pressure of the autoperfused hindquarters or hindlegs and, thus, an effect on presynaptic receptors was not found. The results underscore the importance of in vivo experiments for assessing the therapeutic significance of drug-induced stimulation of presynaptic receptors.", "contents": "Studies on the possible contribution of a peripheral presynaptic action of clonidine and dopamine to their vascular effects under in vivo conditions. The functional consequences of drug-induced stimulation under in vivo conditions of alpha-adrenoceptors and dopamine receptors at vascular adrenergic nerve endings (presynaptic receptors) was studied in the autoperfused hindquarters or hindlegs of cats anaesthetized with urethane. The changes in perfusion pressure in response to electrical stimulation of the lumbar sympathetic chain were taken as a measure of noradrenaline release from the vascular adrenergic nerves. Presynaptic inhibitory alpha-adrenoceptors and dopamine receptors were activated by clonidine and dopamine, respectively. According to in vitro experiments these two drugs are more potent stimulants of peripheral presynaptic than postsynaptic receptors. The lowest frequency of stimulation of the lumbar sympathetic chain which yielded a reproducible pressor response was 4 HZ for the autoperfused hindquarters and 1 HZ for the hindlegs; Clonidine was tested over a wide dose range (1-100 mug/kg i;v). A reduction of the stimulation-induced pressor response in the autoperfused hindquarters or hindlegs was observed only after the rather high dose of 100 mug/kg of clonidine. The inhibition was marked at low frequencies of stimulation (1-4 HZ) and weak or absent at high frequencies (16 and 32 HZ). The dose of clonidine (100 mug/kg) which proved to be effective at presynaptic receptors produced a transient increase in blood pressure and in perfusion pressure of the hindquarters and hindlegs and virtually abolished spontaneous sympathetic nervous activity. In spinal cats, the clonidine-induced increases in blood pressure and perfusion pressure were very pronounced and of rather long duration. Thus, under in vivo conditions clonidine showed no selectivity for presynaptic alpha-adrenoceptors in a blood-perfused vascular bed, and its presynaptic action was negligible as compared to its powerful central sympatho-inhibitory effect. Dopamine was constantly infused into the auto-perfused hindquarters or hindlegs at increasing rates until a vasoconstriction due to stimulation of vascular (postsynaptic) alpha-adrenoceptors occurred. The monoamine did not inhibit the stimulation-induced increases in perfusion pressure of the autoperfused hindquarters or hindlegs and, thus, an effect on presynaptic receptors was not found. The results underscore the importance of in vivo experiments for assessing the therapeutic significance of drug-induced stimulation of presynaptic receptors."}
{"id": "PMID:189226", "title": "Scanning electron microscopic studies on the cytolytic effect of phallolysin on isolated rat hepatocytes and AS-30 D hepatoma cells.", "content": "Rat hepatocytes and AS-30 D hepatoma cells were treated in vitro with phallolysin, the toxic haemolysin from the death cap fungus Amanita phalloides. Scanning electron microscopy revealed dose-dependent formation of bulky protrusions on the cell surface, which later on burst, expelling intracellular material into the surrounding medium, while the cells became stainable with trypan blue. After 1 haemolytic unit (HU)/ml the protrusions burst within 10 min; after 3 HU/ml all cells were destroyed within 3-5 min. Susceptibility of hepatoma cells did not differ from that of hepatocytes.", "contents": "Scanning electron microscopic studies on the cytolytic effect of phallolysin on isolated rat hepatocytes and AS-30 D hepatoma cells. Rat hepatocytes and AS-30 D hepatoma cells were treated in vitro with phallolysin, the toxic haemolysin from the death cap fungus Amanita phalloides. Scanning electron microscopy revealed dose-dependent formation of bulky protrusions on the cell surface, which later on burst, expelling intracellular material into the surrounding medium, while the cells became stainable with trypan blue. After 1 haemolytic unit (HU)/ml the protrusions burst within 10 min; after 3 HU/ml all cells were destroyed within 3-5 min. Susceptibility of hepatoma cells did not differ from that of hepatocytes."}
{"id": "PMID:189227", "title": "Ca2+ -uptake into noradrenaline-storing granules of bovine splenic nerves.", "content": "Noradrenaline-storing granules, a mitochondrial fraction and a microsomal fraction of bovine splenic nerve trunks were prepared by differential centrifugation. These particulate fractions were characterized by their noradrenaline content, succinate dehydrogenase and glucose-6-phosphatase activity. In the presence of ATP-Mg2+ all three fractions accumulated 45Ca2+ during incubation with 0.1 mM 45 CaCl2, buffered with potassium phosphate or glycylglycine (pH 7.5; 28 degrees C). The accumulated 45 Ca2+ was not removable by EGTA, and the uptake was absent at 0 degrees C or after destruction of the particles by sonication. The behaviour of the 45 Ca2+ -uptake into all three fractions against varying ATP-concentrations, metabolic inhibitors (pentachlorophenol, desaspidine, 2,4-dinitrophenol, N-ethylmaleimide, p-chloromercuribenzoate, sodium azide, amobarbital) and drugs (phenoxybenzamine, verapamil, prenylamine, reserpine, bretylium, phentolamine) was studied. Under nearly all conditions there were differences between the 45 Ca2+ -uptake into mitochondria and that into microsomes, which suggests two distinct uptake processes. The 45 Ca2+ -uptake into the granule fraction behaved intermediate between the two other fractions under many conditions, but not under all. Therefore, it is not possible to explain the 45 Ca2+ -uptake into the granule fraction as being due to contamination with mitochondria and microsomes; an inherent ATP-Mg2+ -dependent 45Ca2+ -uptake into the nerve granules must be postulated, which is not directly coupled with the noradrenaline transport into these particles. A particulate fraction (14000-100000 g), containing noradrenaline granules, was prepared from the vas deferens of the rat. Incubation with 5 X 10(-6) M (-)-noradrenaline and 0.1 mM 45Ca2+ showed that the particles of this fraction take up noradrenaline and 45Ca2+. The uptake of both was dependent on ATP-Mg2+. The ATP-Mg2+ -dependent uptake of both noradrenaline and 45Ca2+ was substantially reduced in the corresponding tissue fraction prepared from denervated vasa deferentia.", "contents": "Ca2+ -uptake into noradrenaline-storing granules of bovine splenic nerves. Noradrenaline-storing granules, a mitochondrial fraction and a microsomal fraction of bovine splenic nerve trunks were prepared by differential centrifugation. These particulate fractions were characterized by their noradrenaline content, succinate dehydrogenase and glucose-6-phosphatase activity. In the presence of ATP-Mg2+ all three fractions accumulated 45Ca2+ during incubation with 0.1 mM 45 CaCl2, buffered with potassium phosphate or glycylglycine (pH 7.5; 28 degrees C). The accumulated 45 Ca2+ was not removable by EGTA, and the uptake was absent at 0 degrees C or after destruction of the particles by sonication. The behaviour of the 45 Ca2+ -uptake into all three fractions against varying ATP-concentrations, metabolic inhibitors (pentachlorophenol, desaspidine, 2,4-dinitrophenol, N-ethylmaleimide, p-chloromercuribenzoate, sodium azide, amobarbital) and drugs (phenoxybenzamine, verapamil, prenylamine, reserpine, bretylium, phentolamine) was studied. Under nearly all conditions there were differences between the 45 Ca2+ -uptake into mitochondria and that into microsomes, which suggests two distinct uptake processes. The 45 Ca2+ -uptake into the granule fraction behaved intermediate between the two other fractions under many conditions, but not under all. Therefore, it is not possible to explain the 45 Ca2+ -uptake into the granule fraction as being due to contamination with mitochondria and microsomes; an inherent ATP-Mg2+ -dependent 45Ca2+ -uptake into the nerve granules must be postulated, which is not directly coupled with the noradrenaline transport into these particles. A particulate fraction (14000-100000 g), containing noradrenaline granules, was prepared from the vas deferens of the rat. Incubation with 5 X 10(-6) M (-)-noradrenaline and 0.1 mM 45Ca2+ showed that the particles of this fraction take up noradrenaline and 45Ca2+. The uptake of both was dependent on ATP-Mg2+. The ATP-Mg2+ -dependent uptake of both noradrenaline and 45Ca2+ was substantially reduced in the corresponding tissue fraction prepared from denervated vasa deferentia."}
{"id": "PMID:189228", "title": "On the mechanism of the decrease in cerebellar cyclic GMP content elicited by opiate receptor agonists.", "content": "Morphine, dextromoramide (4 mumol/kg i.p.) and vimonol R2 (17 mumol/kg i.p.) in analgesic doses (28 to 112 mumol/kg i.p.) decreased 3',5'-cyclic guanosine monophosphate (cGMP) in rat cerebellar cortex; morphine also decreased the cGMP content in deep cerebellar nuclei. Intrastriatal but not intracerebellar injections of morphine (20 mug) decreased cerebellar cGMP content. Naltrexone, an opiate receptor antagonist, but only apomorphine, a dopaminergic receptor agonist, blocked the effect of morphine on cerebellar cGMP. Pretreatment with 3-acetylpyridine (3-AP) which destroys the climbing fibers, failed to antagonize the effect of morphine on cerebellar cGMP. These results suggest that activation of opiate receptors in striatum decreases cerebellar cGMP content presumably by reducing activity in the mossy fiber excitatory input to cerebellum.", "contents": "On the mechanism of the decrease in cerebellar cyclic GMP content elicited by opiate receptor agonists. Morphine, dextromoramide (4 mumol/kg i.p.) and vimonol R2 (17 mumol/kg i.p.) in analgesic doses (28 to 112 mumol/kg i.p.) decreased 3',5'-cyclic guanosine monophosphate (cGMP) in rat cerebellar cortex; morphine also decreased the cGMP content in deep cerebellar nuclei. Intrastriatal but not intracerebellar injections of morphine (20 mug) decreased cerebellar cGMP content. Naltrexone, an opiate receptor antagonist, but only apomorphine, a dopaminergic receptor agonist, blocked the effect of morphine on cerebellar cGMP. Pretreatment with 3-acetylpyridine (3-AP) which destroys the climbing fibers, failed to antagonize the effect of morphine on cerebellar cGMP. These results suggest that activation of opiate receptors in striatum decreases cerebellar cGMP content presumably by reducing activity in the mossy fiber excitatory input to cerebellum."}
{"id": "PMID:189229", "title": "Glucocorticoids: effects on prostaglandin release, cyclic AMP levels and glycosaminoglycan synthesis in fibroblast tissue cultures.", "content": "Glucocorticoids (GCs) reduced cyclic AMP levels and inhibited glycosaminoglycan (GAG) synthesis in secondary embryonic mouse fibroblast cultures, when cells were incubated for short periods (30 min). The order of potency was dexamethasone greater than prednisolone greater than hydrocortisone. The effect was more marked, when cyclic AMP levels and GAG synthesis were increased by addition of PGE1. Glucocorticoids exerted no longer an inhibitory effect on cyclic AMP and GAG synthesis in cultures pretreated for 48 h with the steroids. Addition of PGE1 caused a stronger rise in cyclic AMP and GAG synthesis than in controls without GC-preincubation. This enhancement was even more pronounced, when PGE1 was added together with the GCs. The reversal of the inhibitory effect of the GCs into a potentiating effect following preincubation correlated to a reducation of endogenous PGE formation in the cultures. Short-term treatment with GCs did not reduce endogenous PGE levels, but prolonged incubation markedly decreased PGE levels. PGE formation recovered following addition of fresh medium after the 48 h incubation with the steroids, but the amount of PGE formed remained significantly lower than in untreated cultures. Non-glucocorticoid steroid hormones did not decrease PGE levels. The results indicate that the apparent loss of inhibitory activity of GCs on cyclic AMP and GAG synthesis observed after prolonged incubation may result from a reduction of endogenous PGE formation which renders the cells more sensitive to the stimulatory effect of exogenous PGE1.", "contents": "Glucocorticoids: effects on prostaglandin release, cyclic AMP levels and glycosaminoglycan synthesis in fibroblast tissue cultures. Glucocorticoids (GCs) reduced cyclic AMP levels and inhibited glycosaminoglycan (GAG) synthesis in secondary embryonic mouse fibroblast cultures, when cells were incubated for short periods (30 min). The order of potency was dexamethasone greater than prednisolone greater than hydrocortisone. The effect was more marked, when cyclic AMP levels and GAG synthesis were increased by addition of PGE1. Glucocorticoids exerted no longer an inhibitory effect on cyclic AMP and GAG synthesis in cultures pretreated for 48 h with the steroids. Addition of PGE1 caused a stronger rise in cyclic AMP and GAG synthesis than in controls without GC-preincubation. This enhancement was even more pronounced, when PGE1 was added together with the GCs. The reversal of the inhibitory effect of the GCs into a potentiating effect following preincubation correlated to a reducation of endogenous PGE formation in the cultures. Short-term treatment with GCs did not reduce endogenous PGE levels, but prolonged incubation markedly decreased PGE levels. PGE formation recovered following addition of fresh medium after the 48 h incubation with the steroids, but the amount of PGE formed remained significantly lower than in untreated cultures. Non-glucocorticoid steroid hormones did not decrease PGE levels. The results indicate that the apparent loss of inhibitory activity of GCs on cyclic AMP and GAG synthesis observed after prolonged incubation may result from a reduction of endogenous PGE formation which renders the cells more sensitive to the stimulatory effect of exogenous PGE1."}
{"id": "PMID:189230", "title": "Further evidence for the involvement of cAMP in central blood pressure regulation.", "content": "In order to test the hypothesis that the activity of cardiovascular centres is determined by their content of cAMP a number of drugs which influence the activity of either phosphodiestase or adenylcyclase were injected in doses of 100-1000 mug/kg into the lateral cerebral ventricle of cats. The effects on blood pressure and heart rate were studied. The phosphodiesterase inhibitors papaverine, carbocromene, theophylline and caffeine caused hypertension and tachycardia which increased with the dose while the phosphodiesterase activator imidazole exerted opposite effects. Sodium fluoride which activates adenylcyclase increased blood pressure and heart rate substantially. The results confirm the above-mentioned hypothesis.", "contents": "Further evidence for the involvement of cAMP in central blood pressure regulation. In order to test the hypothesis that the activity of cardiovascular centres is determined by their content of cAMP a number of drugs which influence the activity of either phosphodiestase or adenylcyclase were injected in doses of 100-1000 mug/kg into the lateral cerebral ventricle of cats. The effects on blood pressure and heart rate were studied. The phosphodiesterase inhibitors papaverine, carbocromene, theophylline and caffeine caused hypertension and tachycardia which increased with the dose while the phosphodiesterase activator imidazole exerted opposite effects. Sodium fluoride which activates adenylcyclase increased blood pressure and heart rate substantially. The results confirm the above-mentioned hypothesis."}
{"id": "PMID:189240", "title": "[Electrographic manifestations of sleep in the neuronally-isolated cat cortex].", "content": "Electrographic manifestations of sleep were studied in the neuronally isolated cortex prepared after Khananashvili (1961). Development of electrographic sleep-waking manifestations in the neuronally isolated cortex depended on the time passed after cortex isolation. During the first weeks they were not clear, but after 4-6 months it was possible to record all the sleep-waking stages characteristic of the normal animals. During different sleep-waking stages the electrical manifestations in the neuronally isolated cortex occured simultaneously with the signs of sleep in the other, control hemisphere. Most prominent changes during all sleep-waking stages in neuronally isolated cortex occurred in the theta and delta bands, and the less prominent, in the gamma band. The ways of sleep activity propagation in the neuronally isolated cortex are discussed.", "contents": "[Electrographic manifestations of sleep in the neuronally-isolated cat cortex]. Electrographic manifestations of sleep were studied in the neuronally isolated cortex prepared after Khananashvili (1961). Development of electrographic sleep-waking manifestations in the neuronally isolated cortex depended on the time passed after cortex isolation. During the first weeks they were not clear, but after 4-6 months it was possible to record all the sleep-waking stages characteristic of the normal animals. During different sleep-waking stages the electrical manifestations in the neuronally isolated cortex occured simultaneously with the signs of sleep in the other, control hemisphere. Most prominent changes during all sleep-waking stages in neuronally isolated cortex occurred in the theta and delta bands, and the less prominent, in the gamma band. The ways of sleep activity propagation in the neuronally isolated cortex are discussed."}
{"id": "PMID:189241", "title": "[Influence of sympathetic fiber stimulation on conduction of excitation in the cat pterygopalatine ganglion].", "content": "Interaction between excitation passing through parasympathetic and sympathetic pathways was studied by recording of action potentials evoked in postganglionic nerves of the cat pterygopalatine ganglion by both testing stimuli applied to the greater superficial  petrosal nerve and conditioning stimuli applied to cervical sympathetic nerve. Depression of synaptic transmission through the ganglion is shown to take place under stimulation of the cervical sympathetic nerve. The magnitude of such inhibition reached to 13 +/- 3%.", "contents": "[Influence of sympathetic fiber stimulation on conduction of excitation in the cat pterygopalatine ganglion]. Interaction between excitation passing through parasympathetic and sympathetic pathways was studied by recording of action potentials evoked in postganglionic nerves of the cat pterygopalatine ganglion by both testing stimuli applied to the greater superficial  petrosal nerve and conditioning stimuli applied to cervical sympathetic nerve. Depression of synaptic transmission through the ganglion is shown to take place under stimulation of the cervical sympathetic nerve. The magnitude of such inhibition reached to 13 +/- 3%."}
{"id": "PMID:189244", "title": "[Advances in gammaencephalography for the study of intercranial lesions].", "content": "Simultaneously to the development of new techniques such as the computerized axial tomography, the gamma-angioencephalography is progressing in the field of cerebral investigation in its original way, keeping on non invasing character. In view to analyze this evolution we shall examine first its technical possibilities, then the extractible data of the various techniques. Finally we will consider in which way we must bring most of our effort for the best utilization of the gamma-angioencephalography in the routine work, on one hand, and for progressing in the knowledge of the physiopathology of some lesions, specially vascular accidents, on the other hand. Technical modalities are multiple. Besides the standard technique (pertechnetate angiography with rapid sequential views, regional transit curves, early and late static views) it is possible to replace or to repete the injection: --changing the patient's position, --using another radiopharmaceutical labelled with technetium -or another isotope, or two tracers for two compartments; --carrying out a pharmacodynamic or CO2 test, --using radioxenon, and secondly a pure vascular tracer, to measure relative regional blood pool and relative regional blood flow. a) morphological ones (vascular tracks, regional blood pool, radioactive areas: number, form, homogeneity, outline), b) dynamic and quantitative ones (transit times, blood flow, extravascular diffusion, changes of these parameters when changing the radiopharmaceutic, or when using a test). Progresses can take place in three ways, very closely related to each other: a) In the methodology, to precise --relative merit of the different radiocompounds according to the various cerebral lesions, --methods for examination according to the clinical problems, --computing and date processing techniques. b) In the indications, to choose the best, the simplest, though the surest method for the daily clinical problems, and the best one to assemble special information escaping to the morphological radiological techniques. This choice needs frequent and close discussions between clinicians and nuclear specialists. c) In the signification of the data, to interprate correctly: --preferential uptakes in lesions or in compartments, --changes in the relative volumes of vascular bed and extravascular space in lesions, --vascular reactivity to an hemodynamic test, --accumulation or clearance of a diffusible tracer such as xenon. It is not always easy to reach a non equivocal interpretation of a whole group of data. It can be better to give a descriptive analysis which brings together elements for the diagnosis and physiopathological observations helpful for a therapeutic action and to follow up the disease at short and long term.", "contents": "[Advances in gammaencephalography for the study of intercranial lesions]. Simultaneously to the development of new techniques such as the computerized axial tomography, the gamma-angioencephalography is progressing in the field of cerebral investigation in its original way, keeping on non invasing character. In view to analyze this evolution we shall examine first its technical possibilities, then the extractible data of the various techniques. Finally we will consider in which way we must bring most of our effort for the best utilization of the gamma-angioencephalography in the routine work, on one hand, and for progressing in the knowledge of the physiopathology of some lesions, specially vascular accidents, on the other hand. Technical modalities are multiple. Besides the standard technique (pertechnetate angiography with rapid sequential views, regional transit curves, early and late static views) it is possible to replace or to repete the injection: --changing the patient's position, --using another radiopharmaceutical labelled with technetium -or another isotope, or two tracers for two compartments; --carrying out a pharmacodynamic or CO2 test, --using radioxenon, and secondly a pure vascular tracer, to measure relative regional blood pool and relative regional blood flow. a) morphological ones (vascular tracks, regional blood pool, radioactive areas: number, form, homogeneity, outline), b) dynamic and quantitative ones (transit times, blood flow, extravascular diffusion, changes of these parameters when changing the radiopharmaceutic, or when using a test). Progresses can take place in three ways, very closely related to each other: a) In the methodology, to precise --relative merit of the different radiocompounds according to the various cerebral lesions, --methods for examination according to the clinical problems, --computing and date processing techniques. b) In the indications, to choose the best, the simplest, though the surest method for the daily clinical problems, and the best one to assemble special information escaping to the morphological radiological techniques. This choice needs frequent and close discussions between clinicians and nuclear specialists. c) In the signification of the data, to interprate correctly: --preferential uptakes in lesions or in compartments, --changes in the relative volumes of vascular bed and extravascular space in lesions, --vascular reactivity to an hemodynamic test, --accumulation or clearance of a diffusible tracer such as xenon. It is not always easy to reach a non equivocal interpretation of a whole group of data. It can be better to give a descriptive analysis which brings together elements for the diagnosis and physiopathological observations helpful for a therapeutic action and to follow up the disease at short and long term."}
{"id": "PMID:189246", "title": "[Characteristics of brain scintigraphy in pediatric age group and its diagnostic value in brain tumors (author's transl)].", "content": "The diagnostic value of brain scintigraphy in intracranial diseases has been well recognized. Numerous reports have appeared in the literature concerning its use in adult cases. The reports dealing with pediatrics cases, however, are quite limited in number. The major factors limiting such studies in children may be considered as follows; (1) infratentorial tumors are common in this age group, in which its diagnostic accuracy has been believed to be quite low, (2) problems of exlosing children to radiation and (3) difficulty in keeping children in one position for a considerable length of time. These difficulties were almost overcome by the use of 99m Tc with a very short half life and a gamma camera, resulting in increased application of this procedure to children. The purpose of this report is to analyse and discuss the scintigraphical characteristics in children and evaluate the diagnostic value in brain tumors. The subjects consist of 199 non-tumoral cases and 53 cases of verified brain tumors. Following conclusions were obtained: (1) Aging changes are noted in normal brain scintigrams of children. One of them is related to the mode of visualization of the basal structures in lateral views. The cranial base appears to be flat before the age of 4 years. A triangular process then appears at the cranial base, approaching that of adult over the age of 10 years. Another change is related to appearance of the temporal and occipital muscles over the cranial vault and the posterior fossa. This becomes apparent about the age of 7 years and produces such masking effects as to interfere with diagnosis in this region over the age of 10 years. (2) The choroid plexus are visualized in about 10% of cases. (3) In brain tumor cases, the detecting rate is 93% in gliomas, and 73% in non-gliomatous tumors. It is particularly low in congenital tumors.", "contents": "[Characteristics of brain scintigraphy in pediatric age group and its diagnostic value in brain tumors (author's transl)]. The diagnostic value of brain scintigraphy in intracranial diseases has been well recognized. Numerous reports have appeared in the literature concerning its use in adult cases. The reports dealing with pediatrics cases, however, are quite limited in number. The major factors limiting such studies in children may be considered as follows; (1) infratentorial tumors are common in this age group, in which its diagnostic accuracy has been believed to be quite low, (2) problems of exlosing children to radiation and (3) difficulty in keeping children in one position for a considerable length of time. These difficulties were almost overcome by the use of 99m Tc with a very short half life and a gamma camera, resulting in increased application of this procedure to children. The purpose of this report is to analyse and discuss the scintigraphical characteristics in children and evaluate the diagnostic value in brain tumors. The subjects consist of 199 non-tumoral cases and 53 cases of verified brain tumors. Following conclusions were obtained: (1) Aging changes are noted in normal brain scintigrams of children. One of them is related to the mode of visualization of the basal structures in lateral views. The cranial base appears to be flat before the age of 4 years. A triangular process then appears at the cranial base, approaching that of adult over the age of 10 years. Another change is related to appearance of the temporal and occipital muscles over the cranial vault and the posterior fossa. This becomes apparent about the age of 7 years and produces such masking effects as to interfere with diagnosis in this region over the age of 10 years. (2) The choroid plexus are visualized in about 10% of cases. (3) In brain tumor cases, the detecting rate is 93% in gliomas, and 73% in non-gliomatous tumors. It is particularly low in congenital tumors."}
{"id": "PMID:189247", "title": "ACTH and brain RNA: changes in content and labelling of RNA in rat brain stem.", "content": "The influence of synthetic ACTH1-24 and ACTH1-10 on rat brain RNA was studied. ACTH1-24 (5 IU/100 g s.c.) treatment resulted in a small decrease in labelling of brain stem RNA (-12%), measured 30 min after the injection of [5-3H] uridine (100 muCi; s.c.), without affecting the distribution of radioactivity of the acid-soluble precursor pool. Furthermore, a small and transitional reduction of total brain stem RNA was found. Similar treatment of adrenalectomized rats (36 h after surgery) resulted in a marked increase (+ 40%) in labelling of brain stem RNA, without affecting the distribution of radioactivity in the acid-soluble pool. In both intact and adrenalectomized rats, treatment with ACTH1-24 did not affect RNA of cortex cerebrum and cerebellum. ACTH1-10, a fragment of ACTH without corticotropic activity in vivo, exhibited no effect on brain stem RNA in either intact or adrenalectomized rats, nor did corticosterone (1 mg/100 g) affect adrenalectomized rats.", "contents": "ACTH and brain RNA: changes in content and labelling of RNA in rat brain stem. The influence of synthetic ACTH1-24 and ACTH1-10 on rat brain RNA was studied. ACTH1-24 (5 IU/100 g s.c.) treatment resulted in a small decrease in labelling of brain stem RNA (-12%), measured 30 min after the injection of [5-3H] uridine (100 muCi; s.c.), without affecting the distribution of radioactivity of the acid-soluble precursor pool. Furthermore, a small and transitional reduction of total brain stem RNA was found. Similar treatment of adrenalectomized rats (36 h after surgery) resulted in a marked increase (+ 40%) in labelling of brain stem RNA, without affecting the distribution of radioactivity in the acid-soluble pool. In both intact and adrenalectomized rats, treatment with ACTH1-24 did not affect RNA of cortex cerebrum and cerebellum. ACTH1-10, a fragment of ACTH without corticotropic activity in vivo, exhibited no effect on brain stem RNA in either intact or adrenalectomized rats, nor did corticosterone (1 mg/100 g) affect adrenalectomized rats."}
{"id": "PMID:189242", "title": "[Value of angiography in the diagnosis of peripheral nerve tumors].", "content": "In current practice, arteriograpy is already acknowledged, at the present time, as a method of primary importance which cannot be dispensed withfor diagnosis, prognosis and treatment. By opposition, considering pathology of the peripheric nerves, arteriography is often overlooked before chirurgical exploration though it affords the same advantages as in the remaining fields of pathology. Technically our preference goes to selective angiography by direct puncture of humeral or femoral artery. Arteriography will permit:-Visualisation of the location of the tumor close to the major vessels;-Evidence of the exact site of the efferent and afferent pedicles;-Discovery of other localisation. Mostly arteriography helps preoperatively to histological diagnosis. It must be recalled that benign neurinomas often assume a misleading aspect on the tumorography with stagnation of the contrast medium which might suggest malignancy. These benign tumors have three peculiar features: 1. Arteries are observed to stretch out around the lesion but never to narrow. 2. There is no explosive vascularisation ; hypervascularisation appears progressively, is located on the periphery of the lesion, and occupies but a part of the whole area. 3. Veins are not invaded but pushed apart and duly appear in normal timing. This peculiar aspect is quite the opposite of what can be observed in malignant tumors, which are, by far, less frequent.", "contents": "[Value of angiography in the diagnosis of peripheral nerve tumors]. In current practice, arteriograpy is already acknowledged, at the present time, as a method of primary importance which cannot be dispensed withfor diagnosis, prognosis and treatment. By opposition, considering pathology of the peripheric nerves, arteriography is often overlooked before chirurgical exploration though it affords the same advantages as in the remaining fields of pathology. Technically our preference goes to selective angiography by direct puncture of humeral or femoral artery. Arteriography will permit:-Visualisation of the location of the tumor close to the major vessels;-Evidence of the exact site of the efferent and afferent pedicles;-Discovery of other localisation. Mostly arteriography helps preoperatively to histological diagnosis. It must be recalled that benign neurinomas often assume a misleading aspect on the tumorography with stagnation of the contrast medium which might suggest malignancy. These benign tumors have three peculiar features: 1. Arteries are observed to stretch out around the lesion but never to narrow. 2. There is no explosive vascularisation ; hypervascularisation appears progressively, is located on the periphery of the lesion, and occupies but a part of the whole area. 3. Veins are not invaded but pushed apart and duly appear in normal timing. This peculiar aspect is quite the opposite of what can be observed in malignant tumors, which are, by far, less frequent."}
{"id": "PMID:189250", "title": "Cyclic AMP levels in cerebrospinal fluid in manic-melancholic patients.", "content": "The concentrations of adenosine 3'5'-cyclic monophosphate (cyclic AMP) in cerebrospinal fluid (CSF) in manic-melancholic patients were studied. As control groups served patients suffering from other psychiatric disorders as well as neruological and orthopedic patients. The results showed no difference between the various diagnostic groups, including melancholic versus manic patients, unipolar versus bipolar types. The severity of the affective states measured by rating scales showed no correlation to cyclic AMP levels in CSF. The cyclic AMP levels were apparently not influenced by electroconvulsive therapy or treatment with lithium, neuroleptica, or tricyclic antidepressants.", "contents": "Cyclic AMP levels in cerebrospinal fluid in manic-melancholic patients. The concentrations of adenosine 3'5'-cyclic monophosphate (cyclic AMP) in cerebrospinal fluid (CSF) in manic-melancholic patients were studied. As control groups served patients suffering from other psychiatric disorders as well as neruological and orthopedic patients. The results showed no difference between the various diagnostic groups, including melancholic versus manic patients, unipolar versus bipolar types. The severity of the affective states measured by rating scales showed no correlation to cyclic AMP levels in CSF. The cyclic AMP levels were apparently not influenced by electroconvulsive therapy or treatment with lithium, neuroleptica, or tricyclic antidepressants."}
{"id": "PMID:189251", "title": "Juvenile dystonic lipidosis: an unusual form of neurovisceral storage disease.", "content": "An unusual neurovisceral lipid storage disorder in two unrelated juvenile patients manifested itself by dystonia and involuntary movements, with facial grimacing, dysarthria, gait difficulty, and impaired manual dexterity. Supranuclear paresis of vertical gaze and splenomegaly were present. Absent were seizures, major intellectual deterioration, spasticity, or blindness. Histiocytes showed lysosomal storage of various phospholipids, cholesterol, neutral lipids, and autofluorescent material. Appendiceal neurons showed only an increse of phospholipids by histochemistry. Neuronal deposits differed ultrastructurally from these in histiocytes. Leukocyte sphingomyelinase activity was normal. The nosology of this disease and its relationship to so-called juvenile types of Niemann-Pick disease is discussed. The primary metabolic defect in these patients remains unknown.", "contents": "Juvenile dystonic lipidosis: an unusual form of neurovisceral storage disease. An unusual neurovisceral lipid storage disorder in two unrelated juvenile patients manifested itself by dystonia and involuntary movements, with facial grimacing, dysarthria, gait difficulty, and impaired manual dexterity. Supranuclear paresis of vertical gaze and splenomegaly were present. Absent were seizures, major intellectual deterioration, spasticity, or blindness. Histiocytes showed lysosomal storage of various phospholipids, cholesterol, neutral lipids, and autofluorescent material. Appendiceal neurons showed only an increse of phospholipids by histochemistry. Neuronal deposits differed ultrastructurally from these in histiocytes. Leukocyte sphingomyelinase activity was normal. The nosology of this disease and its relationship to so-called juvenile types of Niemann-Pick disease is discussed. The primary metabolic defect in these patients remains unknown."}
{"id": "PMID:189252", "title": "Skeletal muscle pseudohypertrophy in primary amyloidosis.", "content": "Macroglossia and skeletal muscle enlargement with weakness appeared in a 38-year-old male who was shown to have amyloidosis and light chain multiple myeloma. Free lambda light chains were present in serum and urine. Skeletal muscle contained large amounts of amyloid and other amorphous material infiltrating blood vessel walls and connective tissue. Muscle fibers, particularly the type II variety, were diminished in size. Amyloid and similar amorphous material also were present in skin. This patient represents an unusual, but somewhat uniform, type of involvement of the neuromuscular apparatus in nonfamilial primary amyloidosis.", "contents": "Skeletal muscle pseudohypertrophy in primary amyloidosis. Macroglossia and skeletal muscle enlargement with weakness appeared in a 38-year-old male who was shown to have amyloidosis and light chain multiple myeloma. Free lambda light chains were present in serum and urine. Skeletal muscle contained large amounts of amyloid and other amorphous material infiltrating blood vessel walls and connective tissue. Muscle fibers, particularly the type II variety, were diminished in size. Amyloid and similar amorphous material also were present in skin. This patient represents an unusual, but somewhat uniform, type of involvement of the neuromuscular apparatus in nonfamilial primary amyloidosis."}
{"id": "PMID:189253", "title": "Schistosomiasis of the spinal cord.", "content": "Four cases of spinal cord schistosomiasis were characterized by paraparesis, sensory loss, and sphincter disturbances progressing over hours to days. One patient showed deterioration over months and remission after laminectomy, followed by the typical, rapidly progressive deficits. Biopsies on two patients showed granulomatous and necrotizing myelitis. Spontaneous improvement and unremitting deterioration, despite chemotherapy, make evaluation of treatment difficult. A survey of all previously reported cases provided no consistent pattern of response to any treatment modalities. Laminectomy for decompression and diagnosis, administration of antischistosomal medications, and high-dose oral prednisone early in the illness are recommended.", "contents": "Schistosomiasis of the spinal cord. Four cases of spinal cord schistosomiasis were characterized by paraparesis, sensory loss, and sphincter disturbances progressing over hours to days. One patient showed deterioration over months and remission after laminectomy, followed by the typical, rapidly progressive deficits. Biopsies on two patients showed granulomatous and necrotizing myelitis. Spontaneous improvement and unremitting deterioration, despite chemotherapy, make evaluation of treatment difficult. A survey of all previously reported cases provided no consistent pattern of response to any treatment modalities. Laminectomy for decompression and diagnosis, administration of antischistosomal medications, and high-dose oral prednisone early in the illness are recommended."}
{"id": "PMID:189254", "title": "Alloxan diabetic neuropathy: electron microscopic studies.", "content": "Peripheral nerves of diabetic rats were studied 2 years after alloxan injection. We observed demyelination and remyelination, axonal degeneration and regeneration, reduplication of basal laminae around vessels and Schwann's cells, as well as onion bulb formation by proliferated Schwann's cells. Crystalline deposits composed of aggregates of fibrillary electron dense material often occurred in vessel walls and endoneurium of diabetic animals but rarely were seen in nerves from age-matched control animals. Glycogen accumulated in myelinated and unmyelinated axons within mitochondria. Axoplasmic inclusions resembling Lafora's bodies and the inclusions of glycogenosis type IV were frequent and often were accompanied by deposits of particulate glycogen. The findings suggest that the neuropathy in alloxan diabetes is caused by metabolic impairment of anxons, Schwann's cells, and vessels, leading to segmental demyelination and axonal degeneration.", "contents": "Alloxan diabetic neuropathy: electron microscopic studies. Peripheral nerves of diabetic rats were studied 2 years after alloxan injection. We observed demyelination and remyelination, axonal degeneration and regeneration, reduplication of basal laminae around vessels and Schwann's cells, as well as onion bulb formation by proliferated Schwann's cells. Crystalline deposits composed of aggregates of fibrillary electron dense material often occurred in vessel walls and endoneurium of diabetic animals but rarely were seen in nerves from age-matched control animals. Glycogen accumulated in myelinated and unmyelinated axons within mitochondria. Axoplasmic inclusions resembling Lafora's bodies and the inclusions of glycogenosis type IV were frequent and often were accompanied by deposits of particulate glycogen. The findings suggest that the neuropathy in alloxan diabetes is caused by metabolic impairment of anxons, Schwann's cells, and vessels, leading to segmental demyelination and axonal degeneration."}
{"id": "PMID:189255", "title": "Effects of triiodothyronine on oxidative phosphorylation in immature rat brain mitochondria.", "content": "Oxidative phosphorylation was measured polarographically in brain mitochondria isolated from 1 to 3-week-old normal and triiodothyronine-treated rat pups. Adenosine diphosphate (ADP)/oxygen ratios with nicotinamide-adenine dinucleotide (NAD)-linked substrates, but not with succinate, were increased in brain mitochondria from experimental animals at each age. Control ratios and respiratory rates were not affected. Thus, the normal maturational increase in ADP/oxygen ratios with NAD-linked substrates is accelerated in brain mitochondria from rats treated with triiodothyronnie from birth. This effect on efficiency of oxidative phosphorylation is similar to that of throid hormones on other properties of the maturing brain.", "contents": "Effects of triiodothyronine on oxidative phosphorylation in immature rat brain mitochondria. Oxidative phosphorylation was measured polarographically in brain mitochondria isolated from 1 to 3-week-old normal and triiodothyronine-treated rat pups. Adenosine diphosphate (ADP)/oxygen ratios with nicotinamide-adenine dinucleotide (NAD)-linked substrates, but not with succinate, were increased in brain mitochondria from experimental animals at each age. Control ratios and respiratory rates were not affected. Thus, the normal maturational increase in ADP/oxygen ratios with NAD-linked substrates is accelerated in brain mitochondria from rats treated with triiodothyronnie from birth. This effect on efficiency of oxidative phosphorylation is similar to that of throid hormones on other properties of the maturing brain."}
{"id": "PMID:189256", "title": "A neuromuscular transmission block produced by a cancer tissue extract derived from a patient with the myasthenic syndrome.", "content": "The myasthenic syndrome occasionally is associated with bronchogenic carcinoma. The neuromuscular transmission defect in this syndrome is characterized by a reduction of acetylcholine release from motor nerve endings. This paper reports that an acetone extract of cancer tissue from a patient with the syndrome reduces the acetylcholine release from motor nerve endings and produces a neuromuscular transmission defect in the frog nerve-muscle preparation. This suggests that the pathogenic substance(s) contained in the extract may be produced by certain types of bronchogenic carcinoma and may cause the myasthenic syndrome.", "contents": "A neuromuscular transmission block produced by a cancer tissue extract derived from a patient with the myasthenic syndrome. The myasthenic syndrome occasionally is associated with bronchogenic carcinoma. The neuromuscular transmission defect in this syndrome is characterized by a reduction of acetylcholine release from motor nerve endings. This paper reports that an acetone extract of cancer tissue from a patient with the syndrome reduces the acetylcholine release from motor nerve endings and produces a neuromuscular transmission defect in the frog nerve-muscle preparation. This suggests that the pathogenic substance(s) contained in the extract may be produced by certain types of bronchogenic carcinoma and may cause the myasthenic syndrome."}
{"id": "PMID:189257", "title": "Effect of corticosteroids on sciatic nerve-tibialis anterior muscle of rats treated with hemicholinium-3. An experimental approach to a possible mechanism of action of corticosteroids in myasthenia gravis.", "content": "We studied the effect of intraperitoneally administered corticosteroids on the neuromuscular transmission in the sciatic nerve-tibialis anterior muscle preparation of the anesthetized rat stimulated at a rate of 10 Hz. Administered simultaneously with hemicholinium-3 (HC-3), 80 mug per kilogram (that is, half the lethal dose for 50 percent survival), prednisolone and dexamethasone cause a marked reversal of the block of the neuromuscular transmission caused by HC-3. The effect of aldosterone is very small. The blocking action of d-tubocurarine is not antagonized by either prednisolone or dexamethasone. Choline provides total protection against the HC-3 blockade, whereas physostigmine, in a just sublethal dose, is ineffective. We tentatively conclude that in myasthenia gravis the carrier-mediated transport of choline into the nerve endings may be deficient and that the beneficial effect of corticosteroids in this condition is based on their ability to ameliorate the deficient choline transport.", "contents": "Effect of corticosteroids on sciatic nerve-tibialis anterior muscle of rats treated with hemicholinium-3. An experimental approach to a possible mechanism of action of corticosteroids in myasthenia gravis. We studied the effect of intraperitoneally administered corticosteroids on the neuromuscular transmission in the sciatic nerve-tibialis anterior muscle preparation of the anesthetized rat stimulated at a rate of 10 Hz. Administered simultaneously with hemicholinium-3 (HC-3), 80 mug per kilogram (that is, half the lethal dose for 50 percent survival), prednisolone and dexamethasone cause a marked reversal of the block of the neuromuscular transmission caused by HC-3. The effect of aldosterone is very small. The blocking action of d-tubocurarine is not antagonized by either prednisolone or dexamethasone. Choline provides total protection against the HC-3 blockade, whereas physostigmine, in a just sublethal dose, is ineffective. We tentatively conclude that in myasthenia gravis the carrier-mediated transport of choline into the nerve endings may be deficient and that the beneficial effect of corticosteroids in this condition is based on their ability to ameliorate the deficient choline transport."}
{"id": "PMID:189258", "title": "[Cancer of the gastric stump after resection for ulcer].", "content": "Fourteen cases of primary cancer of the gastric stump as a long-term sequel to resection for ulcer are presented. Surgery was undertaken in all cases, though radical intervention was only possible in 6. Questions of diagnosis and surgical tactics associated with this type of neoplasia are discussed. It is felt that early ascertainment could be aided by fibrogastroscopic controls carried out on a large scale at the time of the symptomatological overture. The possibility of preventive examination is also mooted.", "contents": "[Cancer of the gastric stump after resection for ulcer]. Fourteen cases of primary cancer of the gastric stump as a long-term sequel to resection for ulcer are presented. Surgery was undertaken in all cases, though radical intervention was only possible in 6. Questions of diagnosis and surgical tactics associated with this type of neoplasia are discussed. It is felt that early ascertainment could be aided by fibrogastroscopic controls carried out on a large scale at the time of the symptomatological overture. The possibility of preventive examination is also mooted."}
{"id": "PMID:189259", "title": "[Wilms' tumor. Our clinical experience].", "content": "The survival of children with Wilms' tumour is evaluated in 11 males and 12 females treated between 1967 and 1975 in the light of the clinical stage, age at diagnosis, and sex. The subjects were aged from 4 months to 6 years. Six were in stage I, 4 in stage II, 4 in stage III, 7 in stage IV, and 2 in stage V. Survival in stage I was 100% at 36 months and gradually decreased with the stage. Patients aged less than 2 years presented a survival of 50% two years after diagnosis, compared to 24% in those over 2 years old. Sex appears to be irrelevant to prognosis.", "contents": "[Wilms' tumor. Our clinical experience]. The survival of children with Wilms' tumour is evaluated in 11 males and 12 females treated between 1967 and 1975 in the light of the clinical stage, age at diagnosis, and sex. The subjects were aged from 4 months to 6 years. Six were in stage I, 4 in stage II, 4 in stage III, 7 in stage IV, and 2 in stage V. Survival in stage I was 100% at 36 months and gradually decreased with the stage. Patients aged less than 2 years presented a survival of 50% two years after diagnosis, compared to 24% in those over 2 years old. Sex appears to be irrelevant to prognosis."}
{"id": "PMID:189262", "title": "Amniotic fluid adenosine 3',5' - monophosphate in prostaglandin-induced midtrimester abortions.", "content": "Cyclic adenosine 3'5-monophosphate (cAMP) was serially measured in the amniotic fluid (AF) of 9 patients undergoing midtrimester abortions induced by intraamniotic prostaglandins. The results demonstrate an increase in AF cAMP ranging from 2- to 7-fold within the 6 hours of observation. The fetal heart tones were closely monitored by a Doppler instrument and the time from injection of abortifacient to fetal demise (IDT) and to fetal expulsion (IAT) was accurately recorded. No correlation between the rate of AF cAMP increase and IDT or IAT could be demonstrated. The concentration of cAMP in amniotic fluid obtained from patients with fetal demise in utero was lower than that found in AF of fetuses of corresponding gestational age where the fetus was alive. The significance of AF cAMP as a potential indicator of fetal distress is discussed.", "contents": "Amniotic fluid adenosine 3',5' - monophosphate in prostaglandin-induced midtrimester abortions. Cyclic adenosine 3'5-monophosphate (cAMP) was serially measured in the amniotic fluid (AF) of 9 patients undergoing midtrimester abortions induced by intraamniotic prostaglandins. The results demonstrate an increase in AF cAMP ranging from 2- to 7-fold within the 6 hours of observation. The fetal heart tones were closely monitored by a Doppler instrument and the time from injection of abortifacient to fetal demise (IDT) and to fetal expulsion (IAT) was accurately recorded. No correlation between the rate of AF cAMP increase and IDT or IAT could be demonstrated. The concentration of cAMP in amniotic fluid obtained from patients with fetal demise in utero was lower than that found in AF of fetuses of corresponding gestational age where the fetus was alive. The significance of AF cAMP as a potential indicator of fetal distress is discussed."}
{"id": "PMID:189264", "title": "Hodgkin's disease in siblings: a family study.", "content": "Hodgkin's disease may sporadically occur in more than one member of a family. A family in which two siblings were documented to have the nodular sclerosing form of the disease was studied for immunological competency, distribution of HL-A antigens, and Epstein-Barr virus (EBV) antibody titers. All family members examined, except the living individual with HD, had no significant abnormality in humoral and cellular immunity. HL-A antigens previously reported to appear in Hodgkin's disease with increased frequency were not found. Antibody titers to the viral capsid antigen of EBV were normal. Therefore, none of the genetically associated laboratory tests related to cancer (particularly Hodgkin's disease) were found in this family. The evidence from this family thus supports the probable importance of environmental factors in the etiology of Hodgkin's disease, particularly in the nodular sclerosis group.", "contents": "Hodgkin's disease in siblings: a family study. Hodgkin's disease may sporadically occur in more than one member of a family. A family in which two siblings were documented to have the nodular sclerosing form of the disease was studied for immunological competency, distribution of HL-A antigens, and Epstein-Barr virus (EBV) antibody titers. All family members examined, except the living individual with HD, had no significant abnormality in humoral and cellular immunity. HL-A antigens previously reported to appear in Hodgkin's disease with increased frequency were not found. Antibody titers to the viral capsid antigen of EBV were normal. Therefore, none of the genetically associated laboratory tests related to cancer (particularly Hodgkin's disease) were found in this family. The evidence from this family thus supports the probable importance of environmental factors in the etiology of Hodgkin's disease, particularly in the nodular sclerosis group."}
{"id": "PMID:189265", "title": "Bluetongue virus as a cause of hydranencephaly in cattle.", "content": "Hydranencephaly was produced in a foetus and a calf by intra-uterine infection with an attenuated Type 10 bluetongue virus. Laparotomy was performed on the respective dams and the foetuses, respectively 126 days and 138 days old, were inoculated intramuscularly through the uterine wall with 1 ml of a virus suspension containing 5 x 103 tissue culture infective doese. The younger feotus was aborted on Day 262, while the other one was born alive on Day 273. Both foetuses showed marked hydranencephaly.", "contents": "Bluetongue virus as a cause of hydranencephaly in cattle. Hydranencephaly was produced in a foetus and a calf by intra-uterine infection with an attenuated Type 10 bluetongue virus. Laparotomy was performed on the respective dams and the foetuses, respectively 126 days and 138 days old, were inoculated intramuscularly through the uterine wall with 1 ml of a virus suspension containing 5 x 103 tissue culture infective doese. The younger feotus was aborted on Day 262, while the other one was born alive on Day 273. Both foetuses showed marked hydranencephaly."}
{"id": "PMID:189266", "title": "Oral-facial manifestations of Klippel-Trenaunay-Weber syndrome. Report of two cases.", "content": "Two cases of the Klippel-Trenaunay-Weber syndrome are presented. In one of the cases postsurgical complications arose in association with the vascular component of the syndrome complex. Oral surgeons and dentists must remain aware of the potentially serious complications of dental and/or surgical procedures in such cases. Other stigmata of the syndrome are discussed and related to similar conditions.", "contents": "Oral-facial manifestations of Klippel-Trenaunay-Weber syndrome. Report of two cases. Two cases of the Klippel-Trenaunay-Weber syndrome are presented. In one of the cases postsurgical complications arose in association with the vascular component of the syndrome complex. Oral surgeons and dentists must remain aware of the potentially serious complications of dental and/or surgical procedures in such cases. Other stigmata of the syndrome are discussed and related to similar conditions."}
{"id": "PMID:189267", "title": "Formation of amino acids by cobalt-60 irradiation of hydrogen cyanide solutions.", "content": "Aqueous solutions of hydrogen cyanide (0.004-0.1 M) were exposed to cobalt-60 gamma rays. Among the products formed on hydrolysis of the irradiated solution; glycine, alanine, valine, serine, threonine, aspartic acid, and glutamic acid have been identified.", "contents": "Formation of amino acids by cobalt-60 irradiation of hydrogen cyanide solutions. Aqueous solutions of hydrogen cyanide (0.004-0.1 M) were exposed to cobalt-60 gamma rays. Among the products formed on hydrolysis of the irradiated solution; glycine, alanine, valine, serine, threonine, aspartic acid, and glutamic acid have been identified."}
{"id": "PMID:189271", "title": "[Antibodies against the Epstein-Barr Virus nuclear-antigen in children with malignant disease (author's transl)].", "content": "Sera of 25 patients and 50 health children were tested for the presence of antibodies against the Epstein-Barr Virus Nuclear-Antigen (EBNA). We examined 15 children with acute lymphocytic leukemia, who showed a mean arithmatic titer of 1 : 5.33, 1 child with acute myeloblastic leukemia and 1 child with the chronic myeloblastic form showing no reactivity. Two children with lymphogranuloma had titers 1 : 16 and 1 : 32, respectively. 1 patient with lymphoepithelial carcinoma and 5 with lymphosarcoma showed a mean arithmetic titer of 1 : 170.66. Control persons had antibodies against EBNA in the amount of 1 : 2.56. We think that the humoral reactivity against this regularly viral-genome-associated antigen is an additional indicator for the causative role of the Epstein-Barr Virus.", "contents": "[Antibodies against the Epstein-Barr Virus nuclear-antigen in children with malignant disease (author's transl)]. Sera of 25 patients and 50 health children were tested for the presence of antibodies against the Epstein-Barr Virus Nuclear-Antigen (EBNA). We examined 15 children with acute lymphocytic leukemia, who showed a mean arithmatic titer of 1 : 5.33, 1 child with acute myeloblastic leukemia and 1 child with the chronic myeloblastic form showing no reactivity. Two children with lymphogranuloma had titers 1 : 16 and 1 : 32, respectively. 1 patient with lymphoepithelial carcinoma and 5 with lymphosarcoma showed a mean arithmetic titer of 1 : 170.66. Control persons had antibodies against EBNA in the amount of 1 : 2.56. We think that the humoral reactivity against this regularly viral-genome-associated antigen is an additional indicator for the causative role of the Epstein-Barr Virus."}
{"id": "PMID:189273", "title": "Action of human hyperlipemic sera on the biosynthesis of intercellular matrix macromolecules in aorta organ cultures.", "content": "Explants from rabbit aortic media were incubated in MEM medium supplemented with 14C-lysine and with 10 p. 100 hyperlipemic (type IV and V) or normal human serum respectively. The incubated fragments were extracted at increasing ionic strength. The insoluble collagen and elastin were hydrolysed with collagenase and alcoholic potassium hydroxyde respectively. The radioactivity was determined in the extracts and the radioactive labelling profile of proteins was investigated on polyacrylamide gel electrophoresis in SDS. With the exception of the collagenase extract (polymeric collagen) the incorporation of the radioactivity into insoluble collagen is not altered or increases. These the incubation was carried out in the presence of hyperlipemic serum. Incorporation of the radioactivity into insoluble collagen seems not to be altered. These results show a decreased protein synthesis with a relative increase in the biosynthesis of polymeric insoluble collagen in the aortic media incubated in the presence of hyperlipemic serum.", "contents": "Action of human hyperlipemic sera on the biosynthesis of intercellular matrix macromolecules in aorta organ cultures. Explants from rabbit aortic media were incubated in MEM medium supplemented with 14C-lysine and with 10 p. 100 hyperlipemic (type IV and V) or normal human serum respectively. The incubated fragments were extracted at increasing ionic strength. The insoluble collagen and elastin were hydrolysed with collagenase and alcoholic potassium hydroxyde respectively. The radioactivity was determined in the extracts and the radioactive labelling profile of proteins was investigated on polyacrylamide gel electrophoresis in SDS. With the exception of the collagenase extract (polymeric collagen) the incorporation of the radioactivity into insoluble collagen is not altered or increases. These the incubation was carried out in the presence of hyperlipemic serum. Incorporation of the radioactivity into insoluble collagen seems not to be altered. These results show a decreased protein synthesis with a relative increase in the biosynthesis of polymeric insoluble collagen in the aortic media incubated in the presence of hyperlipemic serum."}
{"id": "PMID:189274", "title": "[Immunologic study of human low density lipoproteins].", "content": "The human serum Low Density Lipoproteins (d : 1,020 - 1,055 g/ml) is composed of lipoproteins B and small amount components which can be precipited during an immunological reaction specifically with lipoproteins C antibodies. Moreover the ethyl-ether treatment induces a dissociation of the LDL into several subunits which have different immunological specificities.", "contents": "[Immunologic study of human low density lipoproteins]. The human serum Low Density Lipoproteins (d : 1,020 - 1,055 g/ml) is composed of lipoproteins B and small amount components which can be precipited during an immunological reaction specifically with lipoproteins C antibodies. Moreover the ethyl-ether treatment induces a dissociation of the LDL into several subunits which have different immunological specificities."}
{"id": "PMID:189279", "title": "Radiologic recognition of adriamycin cardiotoxicity.", "content": "A case of congestive heart failure in a child with Wilms' tumor treated Adriamycin is presented and discussed. The role of Adriamycin in the production of cardiotoxicity is reviewed.", "contents": "Radiologic recognition of adriamycin cardiotoxicity. A case of congestive heart failure in a child with Wilms' tumor treated Adriamycin is presented and discussed. The role of Adriamycin in the production of cardiotoxicity is reviewed."}
{"id": "PMID:189280", "title": "Feuerstein and Mims syndrome with resistant rickets.", "content": "A case of Feuerstein-Mims syndrome (naevus sebaceous, convulsions and mental retardation) is described in association with vitamin D resistant reckets.", "contents": "Feuerstein and Mims syndrome with resistant rickets. A case of Feuerstein-Mims syndrome (naevus sebaceous, convulsions and mental retardation) is described in association with vitamin D resistant reckets."}
{"id": "PMID:189281", "title": "The sleep state characteristics of apnea during infancy.", "content": "The sleep state characteristics of infant sleep apnea were studied in 36 twins examined by polygraphy at 40, 44, and 52 weeks after conception. The definition of sleep apnea is dependent upon the length of apnea, sleep state, and post-conceptional age. None of the infants had apnea longer than 20 seconds and apnea of 10 seconds or longer was uncommon. The attack rates for apneas 2 to 4.9 seconds long were highest in REM and lowest in qliet sleep. The attack rates for apneas 5 to 9.9 seconds long were equal in REM and indeterminate and lowest in quiet sleep. The percentage of infants with apnea of 10 seconds or longer at 40 weeks was highest in REM (27%) and indeterminate sleep (42%) and lowest in quiet sleep (12%). At 52 weeks, apnea 10 seconds or longer during REM decreased to 0%. The effect of maturation on apnea varies with sleep state. Over the period from 40 to 52 weeks, quiet sleep apnea was unchanged and indeterminate sleep apnea decreased only between 40 and 44 weeks. Although REM apnea 2 to 4.9 seconds long was unchanged, REM apnea 5 to 9.9 seconds long decreased between 40 and 44 weeks, and REM apnea of 10 seconds or longer decreased from 27% at 40 weeks to 0% at 52 weeks. This suggests that semi-independent apnea turn-on and turn-off mechanism operate during REM sleep. A correlation between brief apneas and the longer apneas was seen only during REM sleep. For all sleep states, there was no correlation between the levels of apnea of 5 seconds or longer at 40, 44, and 52 weeks.", "contents": "The sleep state characteristics of apnea during infancy. The sleep state characteristics of infant sleep apnea were studied in 36 twins examined by polygraphy at 40, 44, and 52 weeks after conception. The definition of sleep apnea is dependent upon the length of apnea, sleep state, and post-conceptional age. None of the infants had apnea longer than 20 seconds and apnea of 10 seconds or longer was uncommon. The attack rates for apneas 2 to 4.9 seconds long were highest in REM and lowest in qliet sleep. The attack rates for apneas 5 to 9.9 seconds long were equal in REM and indeterminate and lowest in quiet sleep. The percentage of infants with apnea of 10 seconds or longer at 40 weeks was highest in REM (27%) and indeterminate sleep (42%) and lowest in quiet sleep (12%). At 52 weeks, apnea 10 seconds or longer during REM decreased to 0%. The effect of maturation on apnea varies with sleep state. Over the period from 40 to 52 weeks, quiet sleep apnea was unchanged and indeterminate sleep apnea decreased only between 40 and 44 weeks. Although REM apnea 2 to 4.9 seconds long was unchanged, REM apnea 5 to 9.9 seconds long decreased between 40 and 44 weeks, and REM apnea of 10 seconds or longer decreased from 27% at 40 weeks to 0% at 52 weeks. This suggests that semi-independent apnea turn-on and turn-off mechanism operate during REM sleep. A correlation between brief apneas and the longer apneas was seen only during REM sleep. For all sleep states, there was no correlation between the levels of apnea of 5 seconds or longer at 40, 44, and 52 weeks."}
{"id": "PMID:189282", "title": "Herpes simplex: a possible cause of brain-stem encephalitis.", "content": "Herpes simplex virus was isolated from the tracheal aspirate of a 10-year-old boy presenting with acute onset of multiple cranial nerve palsies and a mild right hemiparesis. There was also an elevated herpes complement-fixation titer with decrease in the following weeks infection by herpes virus have been debated, we propose that this represents a case of brain-stem encephalitis due to herpes simplex infection. The importance of early diagnosis and evaluation of therapy are emphasized by this case in which the patient recovered completely.", "contents": "Herpes simplex: a possible cause of brain-stem encephalitis. Herpes simplex virus was isolated from the tracheal aspirate of a 10-year-old boy presenting with acute onset of multiple cranial nerve palsies and a mild right hemiparesis. There was also an elevated herpes complement-fixation titer with decrease in the following weeks infection by herpes virus have been debated, we propose that this represents a case of brain-stem encephalitis due to herpes simplex infection. The importance of early diagnosis and evaluation of therapy are emphasized by this case in which the patient recovered completely."}
{"id": "PMID:189285", "title": "Compartmentation of cardiac adenine nucleotides and formation of adenosine.", "content": "After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either 14C-adenine or 14C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 3'5'-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady state conditions the SA of adenosine and cAMP in the perfusate were of the same order of magnitude and proved to be many times higher than the SA of the respective precursor adenine nucleotides. This difference was observed regardless whether adenine or adenosine was used as prelabeling substances. The SA of inosine and hypoxanthine in the perfusate were constantly lower than the SA of adenosine. Cardiac ischemia of 6 min, which resulted in a markedly increased formation of adenosine, led to a pronounced decrease in the SA of adenosine released from the heart. Our findings provide evidence that at least two different adenine nucleotide compartments of the heart severe as precursors for the formation of adenosine and cAMP, one characterized by a high, the other by a lower SA. Under normoxic conditions adenosine and cAMP released into the cardiac perfusate are derived mainly from a nucleotide fraction of high SA, which appears to be rather small. During ischemia a second compartment of much lower SA in addition contributes to the formation of adenosine.", "contents": "Compartmentation of cardiac adenine nucleotides and formation of adenosine. After prelabeling the adenine nucleotides (ATP, ADP, AMP) of isolated perfused guinea pig hearts with either 14C-adenine or 14C-adenosine for 35 min, labeled adenosine, inosine, hypoxanthine and cyclic 3'5'-AMP (cAMP) were continuously released into the cardiac perfusate. Determination of the specific activities (SA) of the adenine nucleotides, cAMP, and their breakdown products (adenosine, inosine, hypoxanthine) in tissue and perfusate revealed: Under steady state conditions the SA of adenosine and cAMP in the perfusate were of the same order of magnitude and proved to be many times higher than the SA of the respective precursor adenine nucleotides. This difference was observed regardless whether adenine or adenosine was used as prelabeling substances. The SA of inosine and hypoxanthine in the perfusate were constantly lower than the SA of adenosine. Cardiac ischemia of 6 min, which resulted in a markedly increased formation of adenosine, led to a pronounced decrease in the SA of adenosine released from the heart. Our findings provide evidence that at least two different adenine nucleotide compartments of the heart severe as precursors for the formation of adenosine and cAMP, one characterized by a high, the other by a lower SA. Under normoxic conditions adenosine and cAMP released into the cardiac perfusate are derived mainly from a nucleotide fraction of high SA, which appears to be rather small. During ischemia a second compartment of much lower SA in addition contributes to the formation of adenosine."}
{"id": "PMID:189286", "title": "The effect of an inhibitor of adenylate cyclase on the development of pyrogen, prostaglandin and cyclic AMP fevers in the rabbit.", "content": "An exotoxin of Bacillus thuringiensis known to inhibit adenylate cyclase in vitro has been used to investigate the role of cyclic AMP in the pathogenesis of fever in the rabbit. Intra-hypothalamic microinjections of the exotoxin are non-pyrogenic and significantly attenuate the hyperthermia caused by intrahypothalamic microinjections of both bacterial pyrogen (endotoxin) and prostaglandin E1. The hyperthermia produced by dibutyrl cyclic AMP is not affected by the exotoxin. These results support the idea that adenylate cyclase is activated during the development of fever in the rabbit.", "contents": "The effect of an inhibitor of adenylate cyclase on the development of pyrogen, prostaglandin and cyclic AMP fevers in the rabbit. An exotoxin of Bacillus thuringiensis known to inhibit adenylate cyclase in vitro has been used to investigate the role of cyclic AMP in the pathogenesis of fever in the rabbit. Intra-hypothalamic microinjections of the exotoxin are non-pyrogenic and significantly attenuate the hyperthermia caused by intrahypothalamic microinjections of both bacterial pyrogen (endotoxin) and prostaglandin E1. The hyperthermia produced by dibutyrl cyclic AMP is not affected by the exotoxin. These results support the idea that adenylate cyclase is activated during the development of fever in the rabbit."}
{"id": "PMID:189287", "title": "[Intranuclear inclusions in giant cell bone tumor. Demonstration by electron microscopy].", "content": "In a case of giant cell tumour of bone, electron microscopy revealed filamentous inclusions within the nuclei of all the giant cells. Although not invariably present in such tumours, their similarity with the nucleocytoplasmic inclusions seen in osteoclasts in Paget's disease is underlined. This raises interesting questions as to their nature and the histogenesis of these disorders.", "contents": "[Intranuclear inclusions in giant cell bone tumor. Demonstration by electron microscopy]. In a case of giant cell tumour of bone, electron microscopy revealed filamentous inclusions within the nuclei of all the giant cells. Although not invariably present in such tumours, their similarity with the nucleocytoplasmic inclusions seen in osteoclasts in Paget's disease is underlined. This raises interesting questions as to their nature and the histogenesis of these disorders."}
{"id": "PMID:189296", "title": "The missed menstrual period.", "content": "The most likely cause of a missed menstrual period in a woman of childbearing age is pregnancy, stress, or the effects of the pill. If fear of pregnancy is the basis of the problem, simply reassuring the patient that menstrual extraction is available may bring spontaneous resolution.", "contents": "The missed menstrual period. The most likely cause of a missed menstrual period in a woman of childbearing age is pregnancy, stress, or the effects of the pill. If fear of pregnancy is the basis of the problem, simply reassuring the patient that menstrual extraction is available may bring spontaneous resolution."}
{"id": "PMID:189292", "title": "Effect of drugs stimulating dopaminergic system on phosphodiesterase activity in rat striatum.", "content": "Two forms of phosphodiesterase exist in the rat striatum, one with high (PDE -- I), and one with low (PDE -- II) affinity to substrate (cyclic 3',5'-AMP). The results obtained suggest that inhibition of PDE -- I activity by apomorphine or amantadine is partially related to their stimulating effect on dopaminergic system in the striatum.", "contents": "Effect of drugs stimulating dopaminergic system on phosphodiesterase activity in rat striatum. Two forms of phosphodiesterase exist in the rat striatum, one with high (PDE -- I), and one with low (PDE -- II) affinity to substrate (cyclic 3',5'-AMP). The results obtained suggest that inhibition of PDE -- I activity by apomorphine or amantadine is partially related to their stimulating effect on dopaminergic system in the striatum."}
{"id": "PMID:189291", "title": "Central action of nomifensine.", "content": "Nomifensine, a new antidepressant drug, affects the central noradrenergic neurons in the rat. Nomifensine does not affect the noradrenaline level in the brain, but retards the depletion of noradrenaline after inhibition of its synthesis. Apomorphine and dimethylaminoadamantane accelerate the depletion of noradrenaline and amphetamine does not affect it. Nomifensine potentiates the flexor reflex of the hind paw of a spinal rat and depresses the body temperature.", "contents": "Central action of nomifensine. Nomifensine, a new antidepressant drug, affects the central noradrenergic neurons in the rat. Nomifensine does not affect the noradrenaline level in the brain, but retards the depletion of noradrenaline after inhibition of its synthesis. Apomorphine and dimethylaminoadamantane accelerate the depletion of noradrenaline and amphetamine does not affect it. Nomifensine potentiates the flexor reflex of the hind paw of a spinal rat and depresses the body temperature."}
{"id": "PMID:189293", "title": "The role of peptides in the central nervous system function.", "content": "The role of peptides such as fibrinogen degradation products (FDP), albumin degradation products (ADP), globulin degradation products (GDP), Bradykinin (BRS) and Angiotensin II (A) in CNS function is presented. Peptides change the activity of the CNS, of the centrally acting drugs and of some neuromediators. The mechanism of the phenomena observed is discussed.", "contents": "The role of peptides in the central nervous system function. The role of peptides such as fibrinogen degradation products (FDP), albumin degradation products (ADP), globulin degradation products (GDP), Bradykinin (BRS) and Angiotensin II (A) in CNS function is presented. Peptides change the activity of the CNS, of the centrally acting drugs and of some neuromediators. The mechanism of the phenomena observed is discussed."}
{"id": "PMID:189299", "title": "[Hyperlipoproteinemia in children. Correlation between changes in the parents and newborn infant].", "content": "The families of 13 children who had presented hyperlipoproteinemia at birth were studied. Total cholesterol, LDL cholesterol, triglycerides and electrophoresis of LP were performed. The parameters studied were divided in three groups: a) Inespecific indicators (alpha-LP, betas/alphas relation). b) Indicators of the beta-LP group (total and LDL cholesterol and beta-LP). c) Indicators of the prebeta-LP group (TG, prebeta-LP and prebeta-1). In all cases at least one of the parents had hyperlipoproteinemia. All the parents, but one, showed alterations in the same group of indicators as their children. Obesity, diabetes mellitus, arterial hypertension, coronary insufficiency, myocardial infarction and cerebrovascular accident where observed in the families of the hiperlipidemic parents, but not on those of the normolipemic parents.", "contents": "[Hyperlipoproteinemia in children. Correlation between changes in the parents and newborn infant]. The families of 13 children who had presented hyperlipoproteinemia at birth were studied. Total cholesterol, LDL cholesterol, triglycerides and electrophoresis of LP were performed. The parameters studied were divided in three groups: a) Inespecific indicators (alpha-LP, betas/alphas relation). b) Indicators of the beta-LP group (total and LDL cholesterol and beta-LP). c) Indicators of the prebeta-LP group (TG, prebeta-LP and prebeta-1). In all cases at least one of the parents had hyperlipoproteinemia. All the parents, but one, showed alterations in the same group of indicators as their children. Obesity, diabetes mellitus, arterial hypertension, coronary insufficiency, myocardial infarction and cerebrovascular accident where observed in the families of the hiperlipidemic parents, but not on those of the normolipemic parents."}
{"id": "PMID:189301", "title": "Effects of pressure on visible spectra of complexes of myoglobin, hemoglobin, cytochrome c, and horse radish peroxidase.", "content": "The spectra of the ferric form of most heme proteins [metmyoglobin, methemoglobin, horse radish peroxidase (EC 1.11.1.7), and ferricytochrome c at pH 1.5] are converted from high-spin (open crevice) structure to low-spin (closed crevice) form under pressure. Pressures up to 8000 kg/cm2 (780 MPa) have no effect on the spectra of high-spin ferro- and ferricytochrome c, which have a closed crevice structure at pH 7.0. Spectra of deoxy-ferromyoglobin and deoxy-ferrohemoglobin are reduced in intensity, but pressure does not change the positions of the absorption maxima. Cyanide ion prevents pressure-induced spectral changes in metmyoglobin and methemoglobin up to 8000 kg/cm2. Carbon monoxide (with a high affinity for the ferro heme iron) has a similar effect on ferromyoglobin and ferrohemoglobin. The pressure required to cause spectral changes in the heme proteins falls in the order, cytochrome c (pH 7.0) greater than horse radish peroxidase greater than myoglobin greater than hemoglobin. We have calculated a volume change of --50 cm3/mol associated with the configurational change accompanying the reformation of the iron-methionine bond in cytochrome c at low pH.", "contents": "Effects of pressure on visible spectra of complexes of myoglobin, hemoglobin, cytochrome c, and horse radish peroxidase. The spectra of the ferric form of most heme proteins [metmyoglobin, methemoglobin, horse radish peroxidase (EC 1.11.1.7), and ferricytochrome c at pH 1.5] are converted from high-spin (open crevice) structure to low-spin (closed crevice) form under pressure. Pressures up to 8000 kg/cm2 (780 MPa) have no effect on the spectra of high-spin ferro- and ferricytochrome c, which have a closed crevice structure at pH 7.0. Spectra of deoxy-ferromyoglobin and deoxy-ferrohemoglobin are reduced in intensity, but pressure does not change the positions of the absorption maxima. Cyanide ion prevents pressure-induced spectral changes in metmyoglobin and methemoglobin up to 8000 kg/cm2. Carbon monoxide (with a high affinity for the ferro heme iron) has a similar effect on ferromyoglobin and ferrohemoglobin. The pressure required to cause spectral changes in the heme proteins falls in the order, cytochrome c (pH 7.0) greater than horse radish peroxidase greater than myoglobin greater than hemoglobin. We have calculated a volume change of --50 cm3/mol associated with the configurational change accompanying the reformation of the iron-methionine bond in cytochrome c at low pH."}
{"id": "PMID:189302", "title": "Effect of phosphorylation of smooth muscle myosin on actin activation and Ca2+ regulation.", "content": "A 35--70% ammonium sulfate fraction of smooth muscle actomyosin was prepared from guinea pig vas deferens. This fraction also contains a smooth muscle myosin kinase and a phosphatase that phosphorylates and dephosphorylates, respectively, the 20,000-dalton light chain of smooth muscle myosin. Phosphorylated and dephosphorylated smooth muscle myosin. Phosphorylated and dephosphorylated smooth muscle myosin were purified from this ammonium sulfate fraction by gel filtration, which also separated the kinase and the phosphatase from the myosin. Purified phosphorylated and dephosphorylated myosin have identical stained patterns after sodium dodecyl sulfate/polyacrylamide gel electrophoresis. They also have similar ATPase activities measured in 0.5 M KCl in the presence of K+-EDTA and Ca2+. However, the actin-activated myosin ATPase activity is markedly increased after phosphorylation. Moreover, the actin-activated ATPase activity of phosphorylated myosin is inhibited by the removal of Ca2+ in the absence of any added regulatory proteins. Dephosphorylation of myosin results in a decrease in the actin-activated ATPase activity. Skeletal muscle tropomyosin markedly increased the actin-activated ATPase activity of phosphorylated but not dephosphorylated myosin in the presence, but not in the absence, of Ca2+.", "contents": "Effect of phosphorylation of smooth muscle myosin on actin activation and Ca2+ regulation. A 35--70% ammonium sulfate fraction of smooth muscle actomyosin was prepared from guinea pig vas deferens. This fraction also contains a smooth muscle myosin kinase and a phosphatase that phosphorylates and dephosphorylates, respectively, the 20,000-dalton light chain of smooth muscle myosin. Phosphorylated and dephosphorylated smooth muscle myosin. Phosphorylated and dephosphorylated smooth muscle myosin were purified from this ammonium sulfate fraction by gel filtration, which also separated the kinase and the phosphatase from the myosin. Purified phosphorylated and dephosphorylated myosin have identical stained patterns after sodium dodecyl sulfate/polyacrylamide gel electrophoresis. They also have similar ATPase activities measured in 0.5 M KCl in the presence of K+-EDTA and Ca2+. However, the actin-activated myosin ATPase activity is markedly increased after phosphorylation. Moreover, the actin-activated ATPase activity of phosphorylated myosin is inhibited by the removal of Ca2+ in the absence of any added regulatory proteins. Dephosphorylation of myosin results in a decrease in the actin-activated ATPase activity. Skeletal muscle tropomyosin markedly increased the actin-activated ATPase activity of phosphorylated but not dephosphorylated myosin in the presence, but not in the absence, of Ca2+."}
{"id": "PMID:189303", "title": "Isolation from normal and Rous sarcoma virus-transformed chicken fibroblasts of a factor that binds glucose and stimulates its transport.", "content": "A glucose binding fraction was obtained by sucrose gradient centrifugation and Sephadex G-200 chromatopgraphy from confluent normal cells and Rous sarcoma virus-transformed fibroblasts. It was more or less loosely bound to the membrane fraction, most strongly in sarcoma cells, and most loosely in slowly growing confluent fibroblasts. In an average of three determinations, the content of binding factor was increased 2.5-fold in transformed cells, and compared reasonably well to a nearly 4-fold increase in glucose uptake. The addition of 5 mug/ml of purified glucose binding factor to the overlaying fluid in the 100-mm plates increased 7-flod the low glucose uptake of starved fibroblasts. The stimulation was an additive increment to the known stimulation by calf serum.", "contents": "Isolation from normal and Rous sarcoma virus-transformed chicken fibroblasts of a factor that binds glucose and stimulates its transport. A glucose binding fraction was obtained by sucrose gradient centrifugation and Sephadex G-200 chromatopgraphy from confluent normal cells and Rous sarcoma virus-transformed fibroblasts. It was more or less loosely bound to the membrane fraction, most strongly in sarcoma cells, and most loosely in slowly growing confluent fibroblasts. In an average of three determinations, the content of binding factor was increased 2.5-fold in transformed cells, and compared reasonably well to a nearly 4-fold increase in glucose uptake. The addition of 5 mug/ml of purified glucose binding factor to the overlaying fluid in the 100-mm plates increased 7-flod the low glucose uptake of starved fibroblasts. The stimulation was an additive increment to the known stimulation by calf serum."}
{"id": "PMID:189304", "title": "Synthesis and characterization of \"face-to-face\" porphyrins.", "content": "The syntheses of four binary porphyrins, two of which are constrained to a \"face-to-face\" conformation, and their Co2+ and Cu2+ derivatives are described. Electron spin resonance indicates that the intermetallic separation in the binuclear \"face-to-face\" porphyrins is about 6.5-6.8 A. Electronic spectra and proton magnetic resonance spectra support the postulated \"face-to-face\" conformations. A hypothesis that related compounds may serve as multielectron redox catalysts for O2 and N2 is presented.", "contents": "Synthesis and characterization of \"face-to-face\" porphyrins. The syntheses of four binary porphyrins, two of which are constrained to a \"face-to-face\" conformation, and their Co2+ and Cu2+ derivatives are described. Electron spin resonance indicates that the intermetallic separation in the binuclear \"face-to-face\" porphyrins is about 6.5-6.8 A. Electronic spectra and proton magnetic resonance spectra support the postulated \"face-to-face\" conformations. A hypothesis that related compounds may serve as multielectron redox catalysts for O2 and N2 is presented."}
{"id": "PMID:189305", "title": "Nuclear coupling of 33S and the nature of free radicals in irradiated crystals of N-acetyl-L-cysteine.", "content": "Hyperfine structure due to 33S in its natural abundance of 0.76% has been measured in the electron spin resonance of free radicals produced by x-irradiation of single crystals of N-acetyl-L-cysteine at 77 K. These measurements proved that the radicals produced at 77 K with principal g values of 1.990, 2.006, and 2.214 are monosulfide radicals with the 3p unpaired electron density of 0.70 on the S. They are believed to be negatively charged molecules RCH2S-H or neutral RCH2SH2 radicals in which 90% of the spin density of the captured electron is concentrated in a d-p hybrid orbital on the S. As the temperature is raised to 300 K, these, as well as the carbon-centered radicals produced at the lower temperature, are mostly converted to neutral disulfide radicals RCH2SS like those observed in irradiated cystine.", "contents": "Nuclear coupling of 33S and the nature of free radicals in irradiated crystals of N-acetyl-L-cysteine. Hyperfine structure due to 33S in its natural abundance of 0.76% has been measured in the electron spin resonance of free radicals produced by x-irradiation of single crystals of N-acetyl-L-cysteine at 77 K. These measurements proved that the radicals produced at 77 K with principal g values of 1.990, 2.006, and 2.214 are monosulfide radicals with the 3p unpaired electron density of 0.70 on the S. They are believed to be negatively charged molecules RCH2S-H or neutral RCH2SH2 radicals in which 90% of the spin density of the captured electron is concentrated in a d-p hybrid orbital on the S. As the temperature is raised to 300 K, these, as well as the carbon-centered radicals produced at the lower temperature, are mostly converted to neutral disulfide radicals RCH2SS like those observed in irradiated cystine."}
{"id": "PMID:189306", "title": "Electronic properties of the casein-methylglyoxal complex.", "content": "Measurements of the electron spin resonance, direct current conductivity, microwave permittivity, and electronic transference number are reported for the brown casein-methylglyoxal complex. Compared with normal white casein, the colored casein complex exhibits an increased electronic activity. This is considered to arise from the electron-accepting action of the methylglyoxal in separating electronic charge from an otherwise completely occupied electronic ground state of the casein macromolecule.", "contents": "Electronic properties of the casein-methylglyoxal complex. Measurements of the electron spin resonance, direct current conductivity, microwave permittivity, and electronic transference number are reported for the brown casein-methylglyoxal complex. Compared with normal white casein, the colored casein complex exhibits an increased electronic activity. This is considered to arise from the electron-accepting action of the methylglyoxal in separating electronic charge from an otherwise completely occupied electronic ground state of the casein macromolecule."}
{"id": "PMID:189307", "title": "Experimental test of the vibronically coupled tunneling description of biological electron transfer.", "content": "Evidence for the constructs central to vibronically coupled electron transfer has been obtained. Our experiments show the existence of a weak (f congruent to 10(-6)) charge-transfer absorption band in the near infrared for the bound donor-acceptor complex, cytochrome c-Fe(CN)6. Such a charge-transfer band had been predicted from the theory of such transfers. The experimental method, using a form of excitation modulation spectroscopy, measures only the optical absorption that induces charge transfer between the donor and the acceptor (and does not detect other absorptions) and allows the study of charge-transfer bands whose absorbances are small compared to the sample absorbance. The energy position and oscillator strength of the band agree with the general predictions of this vibronically coupled tunneling theory. We suggest that, in this system at room temperature, the electron transfer can be described by this tunneling theory. This model system result gives credence to the short electron transfer distances the theory has predicted for biological electron transfers.", "contents": "Experimental test of the vibronically coupled tunneling description of biological electron transfer. Evidence for the constructs central to vibronically coupled electron transfer has been obtained. Our experiments show the existence of a weak (f congruent to 10(-6)) charge-transfer absorption band in the near infrared for the bound donor-acceptor complex, cytochrome c-Fe(CN)6. Such a charge-transfer band had been predicted from the theory of such transfers. The experimental method, using a form of excitation modulation spectroscopy, measures only the optical absorption that induces charge transfer between the donor and the acceptor (and does not detect other absorptions) and allows the study of charge-transfer bands whose absorbances are small compared to the sample absorbance. The energy position and oscillator strength of the band agree with the general predictions of this vibronically coupled tunneling theory. We suggest that, in this system at room temperature, the electron transfer can be described by this tunneling theory. This model system result gives credence to the short electron transfer distances the theory has predicted for biological electron transfers."}
{"id": "PMID:189308", "title": "Rates of aggregation, loss of anchorage dependence, and tumorigenicity of cultured cells.", "content": "The net rate of spontaneous aggregation of cells suspended with EDTA was measured for various cell types including spontaneous transformants and cells transformed with DNA and RNA viruses. The anchorage dependence as determined by growth in methyl cellulose and the tumorigenicity in vivo were also determined. All cells that had lost their anchorage dependency and were tumorigenic showed a high net rate of spontaneous adhesion. A31 was the only nontransformed cell line to have a high net rate of adhesion. The net rate of spontaneous aggregation of cells is a quick and reliable index of tumorigenicity and offers a new approach to understanding the mechanisms of cell surface changes associated with transformation.", "contents": "Rates of aggregation, loss of anchorage dependence, and tumorigenicity of cultured cells. The net rate of spontaneous aggregation of cells suspended with EDTA was measured for various cell types including spontaneous transformants and cells transformed with DNA and RNA viruses. The anchorage dependence as determined by growth in methyl cellulose and the tumorigenicity in vivo were also determined. All cells that had lost their anchorage dependency and were tumorigenic showed a high net rate of spontaneous adhesion. A31 was the only nontransformed cell line to have a high net rate of adhesion. The net rate of spontaneous aggregation of cells is a quick and reliable index of tumorigenicity and offers a new approach to understanding the mechanisms of cell surface changes associated with transformation."}
{"id": "PMID:189309", "title": "Infectious DNA of spleen necrosis virus is integrated at a single site in the DNA of chronically infected chicken fibroblasts.", "content": "The infectious DNAs of a number of avian leukosis-sarcoma and reticuloendotheliosis viruses were digested with six nucleotide-specific restriction endonucleases, and the digests were tested for infectivity. All of the enzymes inactivated the viral infectivities except for EcoRI, which did not inactivate the infectivity of the DNA of two of the reticuloendotheliosis viruses, spleen necrosis and chick syncytial viruses. The infectious DNA of spleen necrosis virus after digestion with EcoRI had a buoyant density in CsCl solution greater than the density of the high-molecular-weight infectious viral DNA. The infectious EcoRI-digested spleen necrosis virus DNA from chronically infected chicken cells was uniform in size, 10 megadaltons, which indicated a single site of integration. The infectious EcoRI-digested spleen necrosis virus DNA from acutely infected cells was heterogeneous in size, ranging from 8-14 megadaltons, which indicated multiple sites of integration. These results are consistent with the hypothesis that cells that integrate infectious spleen necrosis virus DNA at a single site survive and multiply, whereas cells that integrate infectious viral DNA at additional sites either die or selectively lose or inactivate the DNA in the additional sites.", "contents": "Infectious DNA of spleen necrosis virus is integrated at a single site in the DNA of chronically infected chicken fibroblasts. The infectious DNAs of a number of avian leukosis-sarcoma and reticuloendotheliosis viruses were digested with six nucleotide-specific restriction endonucleases, and the digests were tested for infectivity. All of the enzymes inactivated the viral infectivities except for EcoRI, which did not inactivate the infectivity of the DNA of two of the reticuloendotheliosis viruses, spleen necrosis and chick syncytial viruses. The infectious DNA of spleen necrosis virus after digestion with EcoRI had a buoyant density in CsCl solution greater than the density of the high-molecular-weight infectious viral DNA. The infectious EcoRI-digested spleen necrosis virus DNA from chronically infected chicken cells was uniform in size, 10 megadaltons, which indicated a single site of integration. The infectious EcoRI-digested spleen necrosis virus DNA from acutely infected cells was heterogeneous in size, ranging from 8-14 megadaltons, which indicated multiple sites of integration. These results are consistent with the hypothesis that cells that integrate infectious spleen necrosis virus DNA at a single site survive and multiply, whereas cells that integrate infectious viral DNA at additional sites either die or selectively lose or inactivate the DNA in the additional sites."}
{"id": "PMID:189310", "title": "Assignment of the integration site for simian virus 40 to chromosome 17 in GM54VA, a human cell line transformed by simian virus 40.", "content": "GM54VA human cells transformed by simian virus 40 (SV40) were fused with peritoneal macrophages obtained from three different mouse strains. All 27 hybrid clones studied were positive for SV40 tumor antigen in 100% of their cells and contained human chromosome 17. Human chromosome 17 was the only human chromosome present in five of the hybrid clones. Fusion of GM54VA cells and either thymidine kinase (EC 2.7.1.75)-deficient mouse or Chinese hamster fibroblasts resulted in the growth in hypoxanthine-aminopterin-thymidine medium of hybrid clones positive and negative for SV40 tumor antigen. Counterselection of the hybrid clones positive for tumor antigen in medium containing 5-bromodeoxyuridine resulted in the growth of hybrid cells that were negative for tumor antigen. These experiments indicate that negative for tumor antigen. These experiments indicate that SV40 is integrated in only one of the two parental human chromosomes 17. Because the genome of SV40 has been assigned to human chromosome 7 in two other SV40-transformed human cell lines, at least two different integration sites for SV40 would seem to be present in human cells: one located in human chromosome 7 and the other located in human chromosome 17.", "contents": "Assignment of the integration site for simian virus 40 to chromosome 17 in GM54VA, a human cell line transformed by simian virus 40. GM54VA human cells transformed by simian virus 40 (SV40) were fused with peritoneal macrophages obtained from three different mouse strains. All 27 hybrid clones studied were positive for SV40 tumor antigen in 100% of their cells and contained human chromosome 17. Human chromosome 17 was the only human chromosome present in five of the hybrid clones. Fusion of GM54VA cells and either thymidine kinase (EC 2.7.1.75)-deficient mouse or Chinese hamster fibroblasts resulted in the growth in hypoxanthine-aminopterin-thymidine medium of hybrid clones positive and negative for SV40 tumor antigen. Counterselection of the hybrid clones positive for tumor antigen in medium containing 5-bromodeoxyuridine resulted in the growth of hybrid cells that were negative for tumor antigen. These experiments indicate that negative for tumor antigen. These experiments indicate that SV40 is integrated in only one of the two parental human chromosomes 17. Because the genome of SV40 has been assigned to human chromosome 7 in two other SV40-transformed human cell lines, at least two different integration sites for SV40 would seem to be present in human cells: one located in human chromosome 7 and the other located in human chromosome 17."}
{"id": "PMID:189311", "title": "The humoral immune response of NIH Swiss and SWR/J mice to vaccination with formalinized AKR or Gross murine leukemia virus.", "content": "The humoral immune responses of NIH Swiss and SWR/J mice immunized with formalin-inactivated AKR or Gross murine leukemia virus, respectively, were examined. Both immune sera had high titers of antibodies detectable in radioimmune precipitation assays using [3H]leucine-labeled AKR virus and in radioimmunoassays using purified virion components. The predominant antibody titers were directed against gp71 and pl15(E). The immune response against gp71 was predominantly type-specific, whereas the reactivity with pl15(E) was predominantly group-specific. A weak immune response against p15 was also detected. Both sera were cytotoxic against cells replicating the AKR-Gross virus type but not against cells replicating Friend murine leukemia virus. This cytotoxicity could be specifically blocked with purified gp71 of AKR murine leukemia virus. Sera from immune NIH Swiss mice neutralized AKR virus, but did not neutralize Rauscher, Scripps, or wild mouse leukemia virus.", "contents": "The humoral immune response of NIH Swiss and SWR/J mice to vaccination with formalinized AKR or Gross murine leukemia virus. The humoral immune responses of NIH Swiss and SWR/J mice immunized with formalin-inactivated AKR or Gross murine leukemia virus, respectively, were examined. Both immune sera had high titers of antibodies detectable in radioimmune precipitation assays using [3H]leucine-labeled AKR virus and in radioimmunoassays using purified virion components. The predominant antibody titers were directed against gp71 and pl15(E). The immune response against gp71 was predominantly type-specific, whereas the reactivity with pl15(E) was predominantly group-specific. A weak immune response against p15 was also detected. Both sera were cytotoxic against cells replicating the AKR-Gross virus type but not against cells replicating Friend murine leukemia virus. This cytotoxicity could be specifically blocked with purified gp71 of AKR murine leukemia virus. Sera from immune NIH Swiss mice neutralized AKR virus, but did not neutralize Rauscher, Scripps, or wild mouse leukemia virus."}
{"id": "PMID:189312", "title": "Rauscher-leukemia-virus-related sequences in human DNA: presence in some tissues of some patients with hemotopoietic neoplasias and absence in DNA from other tissues.", "content": "A [3H[cDNA probe synthesized from the RNA genome of Rauscher murine leukemia virus (MuLVR) and purified by hybridization to MuLVR70S RNA was hybridized to DNA from human normal and hemotopoietic neoplasia tissues. This cDNA hybridized completely to its homologous 70S RNA and was free of self-complementary sequences. Sequences complementary to MuLVR cDNA were found in DNA from tissues of some patients with leukemia (2 of 8), Hodgkin's disease (3 of 10), and one patient with multiple myeloma. DNA from spleen and kidney of a patient with nonneoplastic disease did not contain detectable MuLVR-related sequences. These virus-related sequences in the DNA from these neoplastic tissues were related but not identical to MuLVR sequences because differences of approximately 6 degrees in the midpoints of thermal elution profiles were found between the heterologous and homologous duplexes. These nucleotide sequences are not the same as the proviral sequences of baboon type-C virus previously found from some other patients with leukemia [Reitz et al. (1976) Proc. Natl. Acad. Sci. USA 73,2113-2117; Wong-Staal et al. (1976) Nature 262, 190-195], because there is no sequence homology between nucleic acids from MuLVR and baboon virus. The absence of these nucleic acid sequences in many tissues of patients with neoplasia and from the few tissues examined from people with nonneoplastic disease suggests that they are not endogenous elements but are acquired after fertilization. Taken together with the previous detection of baboon and woolly monkey type-C viral related components in some human tumors, the results suggest acquisition of at least three types of type-C viral sequences in the human population.", "contents": "Rauscher-leukemia-virus-related sequences in human DNA: presence in some tissues of some patients with hemotopoietic neoplasias and absence in DNA from other tissues. A [3H[cDNA probe synthesized from the RNA genome of Rauscher murine leukemia virus (MuLVR) and purified by hybridization to MuLVR70S RNA was hybridized to DNA from human normal and hemotopoietic neoplasia tissues. This cDNA hybridized completely to its homologous 70S RNA and was free of self-complementary sequences. Sequences complementary to MuLVR cDNA were found in DNA from tissues of some patients with leukemia (2 of 8), Hodgkin's disease (3 of 10), and one patient with multiple myeloma. DNA from spleen and kidney of a patient with nonneoplastic disease did not contain detectable MuLVR-related sequences. These virus-related sequences in the DNA from these neoplastic tissues were related but not identical to MuLVR sequences because differences of approximately 6 degrees in the midpoints of thermal elution profiles were found between the heterologous and homologous duplexes. These nucleotide sequences are not the same as the proviral sequences of baboon type-C virus previously found from some other patients with leukemia [Reitz et al. (1976) Proc. Natl. Acad. Sci. USA 73,2113-2117; Wong-Staal et al. (1976) Nature 262, 190-195], because there is no sequence homology between nucleic acids from MuLVR and baboon virus. The absence of these nucleic acid sequences in many tissues of patients with neoplasia and from the few tissues examined from people with nonneoplastic disease suggests that they are not endogenous elements but are acquired after fertilization. Taken together with the previous detection of baboon and woolly monkey type-C viral related components in some human tumors, the results suggest acquisition of at least three types of type-C viral sequences in the human population."}
{"id": "PMID:189313", "title": "Transient induction of a nuclear antigen unrelated to Epstein-Barr nuclear antigen in cells of two human B-lymphoma lines converted by Epstein-Barr virus.", "content": "Infection of cells of the Epstein-Barr virus (EBV)-negative human B-lymphoma lines BJAB and Ramos with EBV preparations from P3HR-1 or B 95-8 cells converted these cells to EBV genome carriers expressing Epstein-Barr nuclear antigen (EBNA) in almost 100% of these cells. Induction of these cells as well as of clones from P3HR-1 EBV-converted BJAB cells with iododeoxyuridine, aminopterin, and hypoxanthine resulted in the appearance of a nuclear antigen in about 1-6% of the cells 1-4 days after induction. The antigen is different from known EBV-induced antigens like EBNA, viral capsid antigen (VCA) or the D- and R-subspecificities of the early antigen (EA) complex. It is demonstrated by indirect immunofluorescence and inactivated after acetone fixation. The antigen was not detectable after induction of uninfected BJAB and Ramos cells nor has it been found in noninduced or induced P3HR-1 and Raji cells. Thus, it appears that EBV-infection mediates the expression of this antigen, for which the name TINA (transiently induced nuclear antigen) is suggested. Sera reacting against TINA generally contained high antibody titers against EBV-induced EA. Only a limited number of highly EA-reactive sera, however, were also positive for TINA. Among 200 sera tested thus far, TINA reactivity was most frequently observed in sera of patients with nasopharyngeal carcinoma (7 out of 28), in sera of the only two patients with immunoblastoma tested and occasionally in sera from patients with Hodgkin's disease and chronic lymphatic leukemia. Among 70 sera from nontumor patients, TINA reactivity was observed three times: two patients suffered from \"chronic\" infectious mononucleosis, the other revealed persistent splenomegaly.", "contents": "Transient induction of a nuclear antigen unrelated to Epstein-Barr nuclear antigen in cells of two human B-lymphoma lines converted by Epstein-Barr virus. Infection of cells of the Epstein-Barr virus (EBV)-negative human B-lymphoma lines BJAB and Ramos with EBV preparations from P3HR-1 or B 95-8 cells converted these cells to EBV genome carriers expressing Epstein-Barr nuclear antigen (EBNA) in almost 100% of these cells. Induction of these cells as well as of clones from P3HR-1 EBV-converted BJAB cells with iododeoxyuridine, aminopterin, and hypoxanthine resulted in the appearance of a nuclear antigen in about 1-6% of the cells 1-4 days after induction. The antigen is different from known EBV-induced antigens like EBNA, viral capsid antigen (VCA) or the D- and R-subspecificities of the early antigen (EA) complex. It is demonstrated by indirect immunofluorescence and inactivated after acetone fixation. The antigen was not detectable after induction of uninfected BJAB and Ramos cells nor has it been found in noninduced or induced P3HR-1 and Raji cells. Thus, it appears that EBV-infection mediates the expression of this antigen, for which the name TINA (transiently induced nuclear antigen) is suggested. Sera reacting against TINA generally contained high antibody titers against EBV-induced EA. Only a limited number of highly EA-reactive sera, however, were also positive for TINA. Among 200 sera tested thus far, TINA reactivity was most frequently observed in sera of patients with nasopharyngeal carcinoma (7 out of 28), in sera of the only two patients with immunoblastoma tested and occasionally in sera from patients with Hodgkin's disease and chronic lymphatic leukemia. Among 70 sera from nontumor patients, TINA reactivity was observed three times: two patients suffered from \"chronic\" infectious mononucleosis, the other revealed persistent splenomegaly."}
{"id": "PMID:189314", "title": "Identification of virion polypeptides in hamster cells transformed by herpes simplex virus type 1.", "content": "Ten polypeptides were detected on the surface of the virion of herpes simplex virus type 1. Of these ten polypeptides, three were detected in hamster cells transformed by herpes simplex type 1.", "contents": "Identification of virion polypeptides in hamster cells transformed by herpes simplex virus type 1. Ten polypeptides were detected on the surface of the virion of herpes simplex virus type 1. Of these ten polypeptides, three were detected in hamster cells transformed by herpes simplex type 1."}
{"id": "PMID:189315", "title": "Nucleotide sequence of the 5' end of araBAD operon messenger RNA in Escherichia coli B/r.", "content": "The transcription reaction in vitro provides a means of analyzing the nucleotide sequence of the mRNA of the araBAD operon. By controlling the time of synthesis, we obtained araBAD mRNA of varying lengths beginning from the 5' end. These 5' fragments were freed of lambda RNA transcripts by successive hybridizations to the sense strands of a pair of lambda ara transducing phages that carry ara genes in opposite orientations. The purified 5' fragments were ordered by their times of appearance during synchronized RNA elongation and by nearest neighbor analyses. The results, when combined with the knowledge of the NH2-terminal sequence of the product of the first cistron (L-ribulokinase gene araB), establish the nucleotide sequence of the first 69 bases at the 5' end of the araBAD operon mRNA. The AUG starter codon for L-ribulokinase is located at positions 29-31. The sequence is: 5' A-C-C-C-G-U-U-U-U-U-U-U-U-G-G-A-U-G-G-A-G-U-G-A-A-A-C-G-A-U-G-G-C-G-A-U-U-G-C-A-A-U-U-G-G-C-C-U-C-G-A-U-U-U-U-G-C-A-G-U-G-A-U-U-C-U-G-(U)-. . .3'.", "contents": "Nucleotide sequence of the 5' end of araBAD operon messenger RNA in Escherichia coli B/r. The transcription reaction in vitro provides a means of analyzing the nucleotide sequence of the mRNA of the araBAD operon. By controlling the time of synthesis, we obtained araBAD mRNA of varying lengths beginning from the 5' end. These 5' fragments were freed of lambda RNA transcripts by successive hybridizations to the sense strands of a pair of lambda ara transducing phages that carry ara genes in opposite orientations. The purified 5' fragments were ordered by their times of appearance during synchronized RNA elongation and by nearest neighbor analyses. The results, when combined with the knowledge of the NH2-terminal sequence of the product of the first cistron (L-ribulokinase gene araB), establish the nucleotide sequence of the first 69 bases at the 5' end of the araBAD operon mRNA. The AUG starter codon for L-ribulokinase is located at positions 29-31. The sequence is: 5' A-C-C-C-G-U-U-U-U-U-U-U-U-G-G-A-U-G-G-A-G-U-G-A-A-A-C-G-A-U-G-G-C-G-A-U-U-G-C-A-A-U-U-G-G-C-C-U-C-G-A-U-U-U-U-G-C-A-G-U-G-A-U-U-C-U-G-(U)-. . .3'."}
{"id": "PMID:189316", "title": "A protein covalently linked to poliovirus genome RNA.", "content": "Poliovirion [32P]RNA, after digestion with RNase T2, yields mononucleotides and a labeled compound \"X,\" which is not negatively charged at pH 5. X contains, relative to the label in virion RNA, one to two phosphates and is partially acid insoluble. It can be labeled with tritiated amino acids 3 hr after infection, is insoluble in chloroform/methanol, and can be digested with Pronase. These observations suggest that X is a protein. The protein cannot be removed from the polio genome when the RNA is (i) sedimented through a sucrose gradient in 0.5 M NaCl, (ii) heated to 100 degrees in the presence of sodium dodecyl sulfate followed by sedimentation through a sucrose gradient in 80% dimethylsulfoxide, or (iii) banded in 4 M cesium trichloroacetate. Digestion of the 32P-labeled protein with Pronase yields one major 32P-labeled product, which contains pUp. The protein migrates faster than capsid protein VP4 in a polyacrylamide gel. Our data show that the genome of poliovirus, but not poliovirus mRNA [A. Nomoto, Y. F. Lee, and E. Wimmer (1976) Proc. Natl. Acad. Sci. USA 73, 375-380], is covalently attached to a small virus-coded protein (molecular weight less than 7000), which we call VPg. VPg is probably linked to the 5' end of the polio genome. Possible functions of VPg in viral replication are discussed.", "contents": "A protein covalently linked to poliovirus genome RNA. Poliovirion [32P]RNA, after digestion with RNase T2, yields mononucleotides and a labeled compound \"X,\" which is not negatively charged at pH 5. X contains, relative to the label in virion RNA, one to two phosphates and is partially acid insoluble. It can be labeled with tritiated amino acids 3 hr after infection, is insoluble in chloroform/methanol, and can be digested with Pronase. These observations suggest that X is a protein. The protein cannot be removed from the polio genome when the RNA is (i) sedimented through a sucrose gradient in 0.5 M NaCl, (ii) heated to 100 degrees in the presence of sodium dodecyl sulfate followed by sedimentation through a sucrose gradient in 80% dimethylsulfoxide, or (iii) banded in 4 M cesium trichloroacetate. Digestion of the 32P-labeled protein with Pronase yields one major 32P-labeled product, which contains pUp. The protein migrates faster than capsid protein VP4 in a polyacrylamide gel. Our data show that the genome of poliovirus, but not poliovirus mRNA [A. Nomoto, Y. F. Lee, and E. Wimmer (1976) Proc. Natl. Acad. Sci. USA 73, 375-380], is covalently attached to a small virus-coded protein (molecular weight less than 7000), which we call VPg. VPg is probably linked to the 5' end of the polio genome. Possible functions of VPg in viral replication are discussed."}
{"id": "PMID:189317", "title": "Enzymatic synthesis of oligonucleotides of defined sequence: synthesis of a segment of yeast iso-1-cytochrome c gene.", "content": "The deoxyribooligonucleotide, d(pT-T-A-G-C-A-G-A-A-C-C-G-G), constituting a segment of yeast iso-1-cytochrome c gene, has been synthesized by a combination of chemical and primarily enzymatic methods. The starting primer, d(pT-T-A-G1, was chemically synthesized by the phosphodiester method and was extended stepwise, by reactions catalyzed by polynucleotide phosphorylase.", "contents": "Enzymatic synthesis of oligonucleotides of defined sequence: synthesis of a segment of yeast iso-1-cytochrome c gene. The deoxyribooligonucleotide, d(pT-T-A-G-C-A-G-A-A-C-C-G-G), constituting a segment of yeast iso-1-cytochrome c gene, has been synthesized by a combination of chemical and primarily enzymatic methods. The starting primer, d(pT-T-A-G1, was chemically synthesized by the phosphodiester method and was extended stepwise, by reactions catalyzed by polynucleotide phosphorylase."}
{"id": "PMID:189323", "title": "Regulation of behavioral events by thyrotropin releasing factor and cyclic AMP.", "content": "Like dibutyryl cyclic AMP, thyrotropin releasing factor (TRF) has potent antianesthetic properties, but only dibutyryl cyclic AMP shortens narcosis dose-relatedly. In contrast, only TRF reverses amobarbital-induced hypothermia (dose-relatedly). In naive rats, dibutyryl cyclic AMP (25-200 mug) induces convulsions while TRF (5-100 mug) produces intermittent hyperactivity and sedation but never convulsions. To determine whether behavioral events may be regulated in the central nervous system through an interaction of the two naturally occurring compounds, TRF (5-100 mug) and dibutyryl cyclic AMP (25-200 mug) were injected simultaneously into the lateral ventricle of the brain of naive rats or rats anesthetized with amobarbital (80 mg/kg). TRF (12.5-50 mug) and dibutyryl cyclic AMP (100-200 MUG) DID NOT SHORTEN NARCOSIS FURTHER THAN DIBUTYRYL CYCLIC AMP alone. Amobarbital protected against the lethal effects of the two compounds injected simultaneously. Long-lasting locomotor disorders and mortality rate increased with increasing doses of TRF (12.5-25 mug) and dibutyryl cyclic AMP (100-200 MUG) GIVEN TO NAIVE RATS. Results did not support the postulate that cyclic AMP is the second messenger of TRF.", "contents": "Regulation of behavioral events by thyrotropin releasing factor and cyclic AMP. Like dibutyryl cyclic AMP, thyrotropin releasing factor (TRF) has potent antianesthetic properties, but only dibutyryl cyclic AMP shortens narcosis dose-relatedly. In contrast, only TRF reverses amobarbital-induced hypothermia (dose-relatedly). In naive rats, dibutyryl cyclic AMP (25-200 mug) induces convulsions while TRF (5-100 mug) produces intermittent hyperactivity and sedation but never convulsions. To determine whether behavioral events may be regulated in the central nervous system through an interaction of the two naturally occurring compounds, TRF (5-100 mug) and dibutyryl cyclic AMP (25-200 mug) were injected simultaneously into the lateral ventricle of the brain of naive rats or rats anesthetized with amobarbital (80 mg/kg). TRF (12.5-50 mug) and dibutyryl cyclic AMP (100-200 MUG) DID NOT SHORTEN NARCOSIS FURTHER THAN DIBUTYRYL CYCLIC AMP alone. Amobarbital protected against the lethal effects of the two compounds injected simultaneously. Long-lasting locomotor disorders and mortality rate increased with increasing doses of TRF (12.5-25 mug) and dibutyryl cyclic AMP (100-200 MUG) GIVEN TO NAIVE RATS. Results did not support the postulate that cyclic AMP is the second messenger of TRF."}
{"id": "PMID:189324", "title": "Comparison of the analeptic potency of TRH, ACTH 4-10, LHRH, and related peptides.", "content": "Various peptide hormones appear to exert behavioral and pharmacologic effects apart from their classical endocrine actions. Thytrotopin-releasing hormone (TRH), for example, antagonizes the sedation and hypothermia produced by barbiturate and other depressant drugs and de Wied has shown that ACTH 4-10, TRH, LHRH and certain related substances show some activity in inhibition of extinction of a pole-jumping avoidance response in the rat. These data provided the impetus for screening ACTH 4-10, LHRH, and related peptides for analeptic activity. ACTH 4-10 and ACTH 4-7 were inactive in antagonizing pentobarbital whether administered peripherally or centrally. ACTH 4-7 amide and 4-Met(O2), 8-D-Lys,9-Phe-ACTH 4-9 were active regardless of route of administration LHRH and two tripeptide fragments (pGlu-His-Trp-NH, and pGlu-His-Phe-NH2) showed analeptic activity only after intracisternal administration. Thus, some peptide fragments related to ACTH 4-10 and LHRH were shown to share to some degree the analeptic properties previously demonstrated for TRH.", "contents": "Comparison of the analeptic potency of TRH, ACTH 4-10, LHRH, and related peptides. Various peptide hormones appear to exert behavioral and pharmacologic effects apart from their classical endocrine actions. Thytrotopin-releasing hormone (TRH), for example, antagonizes the sedation and hypothermia produced by barbiturate and other depressant drugs and de Wied has shown that ACTH 4-10, TRH, LHRH and certain related substances show some activity in inhibition of extinction of a pole-jumping avoidance response in the rat. These data provided the impetus for screening ACTH 4-10, LHRH, and related peptides for analeptic activity. ACTH 4-10 and ACTH 4-7 were inactive in antagonizing pentobarbital whether administered peripherally or centrally. ACTH 4-7 amide and 4-Met(O2), 8-D-Lys,9-Phe-ACTH 4-9 were active regardless of route of administration LHRH and two tripeptide fragments (pGlu-His-Trp-NH, and pGlu-His-Phe-NH2) showed analeptic activity only after intracisternal administration. Thus, some peptide fragments related to ACTH 4-10 and LHRH were shown to share to some degree the analeptic properties previously demonstrated for TRH."}
{"id": "PMID:189325", "title": "An endogenous inhibitor of N-methyltransferase activity and opiate receptor binding in rabbit tissue.", "content": "We have characterized and purified a peptide extracted from newborn rabbit brain, lung and liver. This peptide has a molecular weight of 1500 and has the ability to inhibit adult rabbit lung N-methyltransferase activity in vitro and can also bind to opiate receptor in rat brain homogenate.", "contents": "An endogenous inhibitor of N-methyltransferase activity and opiate receptor binding in rabbit tissue. We have characterized and purified a peptide extracted from newborn rabbit brain, lung and liver. This peptide has a molecular weight of 1500 and has the ability to inhibit adult rabbit lung N-methyltransferase activity in vitro and can also bind to opiate receptor in rat brain homogenate."}
{"id": "PMID:189326", "title": "Neuroheptapeptide influence on attention and memory in man.", "content": "Twenty normal, male volunteers were administered a subcutaneous injection of either ACTH/MSH 4-10 or diluent and two weeks later received the alternate injection in a complete crossover, double-blind design with order balanced. Subjects were given a battery of psychological tests, including a continuous performance task (CPT), following each injection. Visual evoked responses were recorded during the CPT. Resting, eyes-closed EEGs were also obtained. ACTH/MSH 4-10 improved attention and in so doing improved visual-motor learning and visual, but not verbal, memory, EEG data were consistant with activation of the diffuse thalamic projection system.", "contents": "Neuroheptapeptide influence on attention and memory in man. Twenty normal, male volunteers were administered a subcutaneous injection of either ACTH/MSH 4-10 or diluent and two weeks later received the alternate injection in a complete crossover, double-blind design with order balanced. Subjects were given a battery of psychological tests, including a continuous performance task (CPT), following each injection. Visual evoked responses were recorded during the CPT. Resting, eyes-closed EEGs were also obtained. ACTH/MSH 4-10 improved attention and in so doing improved visual-motor learning and visual, but not verbal, memory, EEG data were consistant with activation of the diffuse thalamic projection system."}
{"id": "PMID:189327", "title": "Peptide enhancement of neuromuscular function: animal and clinical studies.", "content": "Evidence is presented for an extra-adrenal effect of ACTH and ACTH analogs on muscle action potentials (APs), contractions and fatigue in in situ experiments. ACTH, alphaMSH, betaMSH and ACTH 4-10 increase the amplitude of APs and contractions and decrease fatigue in intact, hypophysectomized and in adrenalectomized rats, subjected to repetitive indirect stimulation (supermaximal strength, 5/sec or 10/sec for 30 min). Elevation of endogenous ACTH resulting from adrenalectomy or cold stress, or both, has the same effect as ACTH administration. ACTH peptides are most effective in depressed physiological conditions e.g. following hypophysectomy. As the effect of ACTH 4-10 is abolished after section of the motor nerve, it is inferred that this peptide may affect central motor neurons. Preliminary observations from clinical studies with ACTH 4-10 in patients with muscle disease, in whom a pathological decline in amplitude of a short series of evoked muscle APs was prevented by peptide administration, also indicate a possible action of this peptide on central nervous system neurons.", "contents": "Peptide enhancement of neuromuscular function: animal and clinical studies. Evidence is presented for an extra-adrenal effect of ACTH and ACTH analogs on muscle action potentials (APs), contractions and fatigue in in situ experiments. ACTH, alphaMSH, betaMSH and ACTH 4-10 increase the amplitude of APs and contractions and decrease fatigue in intact, hypophysectomized and in adrenalectomized rats, subjected to repetitive indirect stimulation (supermaximal strength, 5/sec or 10/sec for 30 min). Elevation of endogenous ACTH resulting from adrenalectomy or cold stress, or both, has the same effect as ACTH administration. ACTH peptides are most effective in depressed physiological conditions e.g. following hypophysectomy. As the effect of ACTH 4-10 is abolished after section of the motor nerve, it is inferred that this peptide may affect central motor neurons. Preliminary observations from clinical studies with ACTH 4-10 in patients with muscle disease, in whom a pathological decline in amplitude of a short series of evoked muscle APs was prevented by peptide administration, also indicate a possible action of this peptide on central nervous system neurons."}
{"id": "PMID:189328", "title": "Neuropeptide MSH/ACTH 4-10 enhances attention in the mentally retarded.", "content": "Twenty adult mentally retarded men were randomly assigned to receive MSH/ACTH 4-10 or a vehicle control solution in a double blind procedure. After an intravenous injection the subjects were presented with an orienting sequence and a series of behavioral tests. Treatment with the peptide resulted in a significant decelerative heart rate response during the test stimulus of the orienting sequence. Improved performance of the intradimensional and extradimensional shift of a visual discrimination procedure was significant for subjects receiving MSH/ACTH 4-10. The pattern of response on the subproblem analysis of the extradimensional shift reflected greater dimensional attention in the subjects treated with the peptide. Attentive subjects given MSH/ACTH 4-10 evidenced significant improvement on a rhythm matching test, a test of spatial localization and a visual retention test. The data were interpreted as indicating that the peptide resulted in improved attention of stimulus processing. It was speculated that MSH/ACTH 4-10 may be unquely coded for perceptor/attentional functioning and may be useful as a treatment for disorders of attention.", "contents": "Neuropeptide MSH/ACTH 4-10 enhances attention in the mentally retarded. Twenty adult mentally retarded men were randomly assigned to receive MSH/ACTH 4-10 or a vehicle control solution in a double blind procedure. After an intravenous injection the subjects were presented with an orienting sequence and a series of behavioral tests. Treatment with the peptide resulted in a significant decelerative heart rate response during the test stimulus of the orienting sequence. Improved performance of the intradimensional and extradimensional shift of a visual discrimination procedure was significant for subjects receiving MSH/ACTH 4-10. The pattern of response on the subproblem analysis of the extradimensional shift reflected greater dimensional attention in the subjects treated with the peptide. Attentive subjects given MSH/ACTH 4-10 evidenced significant improvement on a rhythm matching test, a test of spatial localization and a visual retention test. The data were interpreted as indicating that the peptide resulted in improved attention of stimulus processing. It was speculated that MSH/ACTH 4-10 may be unquely coded for perceptor/attentional functioning and may be useful as a treatment for disorders of attention."}
{"id": "PMID:189329", "title": "Dorsal hippocampus: a site of action of neuropeptides on avoidance behavior?", "content": "Vasopressin and ACTH 4-10 induce a dose dependent long-term, respectively short-term inhibition of extinction of a pole jumping avoidance response in animals with sham lesions in the antero-dorsal hippocampus. Small lesions, causing a restricted damage in this area of the brain, partly inhibit the behavioral effect of vasopressin. Extensive lesions in the antero-dorsal hippocampus completely prevent the inhibitory effects of vasopressin and of ACTH 4-10 on extinction of the avoidance response. The extensive lesions in the dorsal hippocampus complex do not interfere with the rate of extinction, but acquisition of the response is retarded. These observations do not allow the conclusion that the hippocampal complex is the locus of action of neuropeptides in relation to avoidance behavior; it is more likely that this brain region is but one site of behavioral action of these hormones, and that the limbic system needs to be intact to permit the neuropeptides to exert their behavioral effects.", "contents": "Dorsal hippocampus: a site of action of neuropeptides on avoidance behavior? Vasopressin and ACTH 4-10 induce a dose dependent long-term, respectively short-term inhibition of extinction of a pole jumping avoidance response in animals with sham lesions in the antero-dorsal hippocampus. Small lesions, causing a restricted damage in this area of the brain, partly inhibit the behavioral effect of vasopressin. Extensive lesions in the antero-dorsal hippocampus completely prevent the inhibitory effects of vasopressin and of ACTH 4-10 on extinction of the avoidance response. The extensive lesions in the dorsal hippocampus complex do not interfere with the rate of extinction, but acquisition of the response is retarded. These observations do not allow the conclusion that the hippocampal complex is the locus of action of neuropeptides in relation to avoidance behavior; it is more likely that this brain region is but one site of behavioral action of these hormones, and that the limbic system needs to be intact to permit the neuropeptides to exert their behavioral effects."}
{"id": "PMID:189330", "title": "Effects of neonatal cerebral ventricular injection of ACTH 4-9 and subsequent adult injections on learning in male and female albino rats.", "content": "An investigation of permanent developmental effects of a potent, long acting ACTH/MSH 4-10 analogue (Organon 2766) on adult passive avoidance performance and of subsequent peripheral adult injections of the same substance on visual (black and white) discrimination learning and reversal in a Thompson-Bryant box was conducted. A subproblem analysis of visual and position preferences during reversal was performed. No differences in passive avoidance performance or in original discrimination learning were obtained. Both infant and adult treatments enhanced reversal learning and visual orientation (proportion of responese to the previously positive stimulus). Infant treatment suppressed position orientation in males and enhanced position orientation in females. These effects were interpreted as indicating that ACTH-like peptides enhance attention to the relevant stimulus by a direct effect on the brain.", "contents": "Effects of neonatal cerebral ventricular injection of ACTH 4-9 and subsequent adult injections on learning in male and female albino rats. An investigation of permanent developmental effects of a potent, long acting ACTH/MSH 4-10 analogue (Organon 2766) on adult passive avoidance performance and of subsequent peripheral adult injections of the same substance on visual (black and white) discrimination learning and reversal in a Thompson-Bryant box was conducted. A subproblem analysis of visual and position preferences during reversal was performed. No differences in passive avoidance performance or in original discrimination learning were obtained. Both infant and adult treatments enhanced reversal learning and visual orientation (proportion of responese to the previously positive stimulus). Infant treatment suppressed position orientation in males and enhanced position orientation in females. These effects were interpreted as indicating that ACTH-like peptides enhance attention to the relevant stimulus by a direct effect on the brain."}
{"id": "PMID:189331", "title": "Effects of ACTH peptide fragments on memory formation.", "content": "The effects of peptides derived from ACTH on the formation of long-term memory have been investigated in male mice. Post-training administration of ACTH 4-10-L-Phe-7 (ACTH-L) improved retention for both passive and active avoidance tasks. Administration of ACTH 4-10-D-Phe-7 (ACTH-D) impaired retention for both tasks. The optimum dose for ACTH-L was about 0.3 mg/kg; the optimum dose for ACTH-D was in the range of 1.0-3.0 mg/kg. Using the passive avoidance task, it was shown that either drug had to be administered within 60 min of training to be highly effective. Amnesia produced by anisomycin (Ani), an inhibitor of protein synthesis, was lessened by ACTH-L and increased by ACTH-D, ACTH-D opposed the memory facilitating effects of ACTH-L. Using intact mice, ACTH-L or ACTH-D did not significantly change the incorporation of valine into protein, nor did these peptides influence the inhibition of protein synthesis caused by anisomycin. The results show that ACTH may play a major role in memory processing, perhaps by facilitating essential protein synthesis at sites specific for the memory being established.", "contents": "Effects of ACTH peptide fragments on memory formation. The effects of peptides derived from ACTH on the formation of long-term memory have been investigated in male mice. Post-training administration of ACTH 4-10-L-Phe-7 (ACTH-L) improved retention for both passive and active avoidance tasks. Administration of ACTH 4-10-D-Phe-7 (ACTH-D) impaired retention for both tasks. The optimum dose for ACTH-L was about 0.3 mg/kg; the optimum dose for ACTH-D was in the range of 1.0-3.0 mg/kg. Using the passive avoidance task, it was shown that either drug had to be administered within 60 min of training to be highly effective. Amnesia produced by anisomycin (Ani), an inhibitor of protein synthesis, was lessened by ACTH-L and increased by ACTH-D, ACTH-D opposed the memory facilitating effects of ACTH-L. Using intact mice, ACTH-L or ACTH-D did not significantly change the incorporation of valine into protein, nor did these peptides influence the inhibition of protein synthesis caused by anisomycin. The results show that ACTH may play a major role in memory processing, perhaps by facilitating essential protein synthesis at sites specific for the memory being established."}
{"id": "PMID:189332", "title": "Reversal of amnesia by an orally active ACTH 4-9 analog (Org 2766).", "content": "The ACTH 4-9 analog, H-Met((O2)-Glu-His-Ph-D-Lys-Phe-OH (Or 2766), attenuates in rats CO2-induced amnesia for a one-trial passive avoidance step-through response when administered prior to the retrieval test but not when given prior to acquisition. Even a dose of 0.001 mug/rat Org 2766 yields an anti-amnesic effect. In this respect Org 2766 is more active than the ACTH fragment ACTH 4-10. An anti-amnesic effect was also obtained when Org 2766 was administered orally. ACTH 4-10 (100 mug/rat) has to be given SC within 8 hr of the retrieval test in order to be effective. A similar time span of effectiveness was observed when Org 2766 was SC injected in a dose of 0.1 mug/rat. The anti-amnesic effect of ACTH 4-10 remains when the time interval between acquisition and retrieval is extended beyond the usual 24 hr. The same appeared to be true for SC ADMINISTERED Org 2766. It is suggested that ACTH-like peptides, and particularly the orally active Org 2766, may be helpful in the treatment of deficient mental performance.", "contents": "Reversal of amnesia by an orally active ACTH 4-9 analog (Org 2766). The ACTH 4-9 analog, H-Met((O2)-Glu-His-Ph-D-Lys-Phe-OH (Or 2766), attenuates in rats CO2-induced amnesia for a one-trial passive avoidance step-through response when administered prior to the retrieval test but not when given prior to acquisition. Even a dose of 0.001 mug/rat Org 2766 yields an anti-amnesic effect. In this respect Org 2766 is more active than the ACTH fragment ACTH 4-10. An anti-amnesic effect was also obtained when Org 2766 was administered orally. ACTH 4-10 (100 mug/rat) has to be given SC within 8 hr of the retrieval test in order to be effective. A similar time span of effectiveness was observed when Org 2766 was SC injected in a dose of 0.1 mug/rat. The anti-amnesic effect of ACTH 4-10 remains when the time interval between acquisition and retrieval is extended beyond the usual 24 hr. The same appeared to be true for SC ADMINISTERED Org 2766. It is suggested that ACTH-like peptides, and particularly the orally active Org 2766, may be helpful in the treatment of deficient mental performance."}
{"id": "PMID:189333", "title": "ACTH 4-10 and short-term memory.", "content": "ACTH 4-10 is a polypeptide which is a fragment of pituitary ACTH and was synthesized by Greven. Studies suggest that it does not have the endocrine or metabolic effects characteristic of ACTH but may have a specific enhancing effect on memory or possibly on attention. Several tasks which emphasized the storage phase of the memory process were presented to young adult (mean age: 23.6 yr) male volunteers. Subjects received 30 mg ACTH 4-10 subcutaneously and their performance on these tasks was compared against placebo. ACTH 4-10 had no effect on unisensory short-term memory. It did, however, impair performance of a bisensory short-term memory task. The bisensory task is complex and requires considerable focussing of attention. It is suggested that ACTH 4-10 may act on the arousal processes which energize behavior unselectively rather than result in focussing of attention.", "contents": "ACTH 4-10 and short-term memory. ACTH 4-10 is a polypeptide which is a fragment of pituitary ACTH and was synthesized by Greven. Studies suggest that it does not have the endocrine or metabolic effects characteristic of ACTH but may have a specific enhancing effect on memory or possibly on attention. Several tasks which emphasized the storage phase of the memory process were presented to young adult (mean age: 23.6 yr) male volunteers. Subjects received 30 mg ACTH 4-10 subcutaneously and their performance on these tasks was compared against placebo. ACTH 4-10 had no effect on unisensory short-term memory. It did, however, impair performance of a bisensory short-term memory task. The bisensory task is complex and requires considerable focussing of attention. It is suggested that ACTH 4-10 may act on the arousal processes which energize behavior unselectively rather than result in focussing of attention."}
{"id": "PMID:189334", "title": "Cognitive effects of ACTH 4-10 in the elderly.", "content": "The polypeptide ACTH 4-10 has been shown to facilitate learning in animals, and possibly to improve attention and memory in normal human subjects. The purpose of this study was to assess the effects of ACTH 4-10 in cognitively impaired elderly subjects. In a double blind, cross over design, 24 cognitively impaired geriatric outpatients (mean age=71.4, 12 with mild and 12 with severe impairment) received injections of 30 mg or 15 mg ACTH 4-10 or matched placebo on 3 successive days. A cognitive test battery of memory and nonmemory tests was administered each day both before and after treatment. The 30 mg dosage produced a slowing of simple visual RT, a nonsignificant improvement trend in verbal associative memory, and significant, severity dependent facilitation or impairment in day later visual memory. The results suggest that the ACTH 4-10 effects on cognitively impaired elderly are dependent on the dosage and on the baseline cognitive level of the subjects.", "contents": "Cognitive effects of ACTH 4-10 in the elderly. The polypeptide ACTH 4-10 has been shown to facilitate learning in animals, and possibly to improve attention and memory in normal human subjects. The purpose of this study was to assess the effects of ACTH 4-10 in cognitively impaired elderly subjects. In a double blind, cross over design, 24 cognitively impaired geriatric outpatients (mean age=71.4, 12 with mild and 12 with severe impairment) received injections of 30 mg or 15 mg ACTH 4-10 or matched placebo on 3 successive days. A cognitive test battery of memory and nonmemory tests was administered each day both before and after treatment. The 30 mg dosage produced a slowing of simple visual RT, a nonsignificant improvement trend in verbal associative memory, and significant, severity dependent facilitation or impairment in day later visual memory. The results suggest that the ACTH 4-10 effects on cognitively impaired elderly are dependent on the dosage and on the baseline cognitive level of the subjects."}
{"id": "PMID:189340", "title": "Pigmented villonodular synovitis of the temporomandibular joint. Case Report.", "content": "Pigmented villonodular synovitis is a lesion containing giant cells and, because of its tendency to recur, it is easily confused with a malignant process. However, careful review of the histological material will reveal that there is no nuclear atypism or mitotic figures. Also, there have been no reports attributing metastases or death to thid disease. The clinical course of our case was definitely benign.", "contents": "Pigmented villonodular synovitis of the temporomandibular joint. Case Report. Pigmented villonodular synovitis is a lesion containing giant cells and, because of its tendency to recur, it is easily confused with a malignant process. However, careful review of the histological material will reveal that there is no nuclear atypism or mitotic figures. Also, there have been no reports attributing metastases or death to thid disease. The clinical course of our case was definitely benign."}
{"id": "PMID:189341", "title": "Propranolol and morphine.", "content": "The morphine blocking and anticonvulsant effects of propranolol were investigated in mice. Three different convulsant procedures (electroshock, pentylenetetrazol and thebaine) were used. In addition, LD50's of morphine after different doses of propranolol were done. Sotalol was used as a control drug to check which of the effects of propranolol could be regarded as due to beta blockade. Morphine LD50 in mice is not altered by pre-treatment with propranolol. The anticonvulsant characteristics of propranolol are different from those of sotalol, the former acting mainly on the tonic phase of the seizures. This study does not support the hypothesis that propranolol is a morphine antagonist but reinforces the idea that propranolol has definite central nervous system effects.", "contents": "Propranolol and morphine. The morphine blocking and anticonvulsant effects of propranolol were investigated in mice. Three different convulsant procedures (electroshock, pentylenetetrazol and thebaine) were used. In addition, LD50's of morphine after different doses of propranolol were done. Sotalol was used as a control drug to check which of the effects of propranolol could be regarded as due to beta blockade. Morphine LD50 in mice is not altered by pre-treatment with propranolol. The anticonvulsant characteristics of propranolol are different from those of sotalol, the former acting mainly on the tonic phase of the seizures. This study does not support the hypothesis that propranolol is a morphine antagonist but reinforces the idea that propranolol has definite central nervous system effects."}
{"id": "PMID:189342", "title": "Inhibition of catecholamine biosynthesis and memory processes.", "content": "Rats injected with 60 mg/kg of alpha-methyl tyrosine (alpha-MT) immediately after a training in a shuttle box impaired retention of conditioned avoidance response (CAR). DL-Dopa (200 mg/kg) administered 5, 30, 60, and 120 min after alpha-MT treatment counteracted the depressive effect of this drug during the retention test; at longer times it was ineffective. Post-trial injections of 600 mg/kg of diethyldithiocarbamate (DDC) impaired retention of CAR; at a lower dose (300 mg/kg) it had no effect. Administration of alpha-MT (60 mg/kg) immediately after passive avoidance training lowered memory in females but not in males. These results suggest that noradrenaline (NA) is required for memory consolidation processes for about 2 h after training.", "contents": "Inhibition of catecholamine biosynthesis and memory processes. Rats injected with 60 mg/kg of alpha-methyl tyrosine (alpha-MT) immediately after a training in a shuttle box impaired retention of conditioned avoidance response (CAR). DL-Dopa (200 mg/kg) administered 5, 30, 60, and 120 min after alpha-MT treatment counteracted the depressive effect of this drug during the retention test; at longer times it was ineffective. Post-trial injections of 600 mg/kg of diethyldithiocarbamate (DDC) impaired retention of CAR; at a lower dose (300 mg/kg) it had no effect. Administration of alpha-MT (60 mg/kg) immediately after passive avoidance training lowered memory in females but not in males. These results suggest that noradrenaline (NA) is required for memory consolidation processes for about 2 h after training."}
{"id": "PMID:189345", "title": "Determination of the mass of viruses by quantitative electron microscopy.", "content": "The photometric method of quantitative determination of dry mass by electron microscopy has been applied to the study of various types of viruses: animal, plant, insect, and bacterial. The method is applicable to all viruses having a mass of 1 x 10-18g or greater. The molecular weight of viruses can be calculated from the mass value by multiplying it by Avogadro's number. In comparison to other methods of determining the molecular weight of viruses, sedimentation and diffusion, sedimentation equilibrium, light scattering, and electron microscopy counting, the method of quantitative electron microscopy is competitive. In some ways quantitative electron microscopy is superior to other methods for the determination of molecular weight: There is no limitation to the size of the virus, no experimental time involved and no concentration and purity of virus preparations required, and finally it is independent of the geometry of the virion. In one important aspect it is unique when compared to other methods; namely, it affords one the capacity to analyse individual virus particles.", "contents": "Determination of the mass of viruses by quantitative electron microscopy. The photometric method of quantitative determination of dry mass by electron microscopy has been applied to the study of various types of viruses: animal, plant, insect, and bacterial. The method is applicable to all viruses having a mass of 1 x 10-18g or greater. The molecular weight of viruses can be calculated from the mass value by multiplying it by Avogadro's number. In comparison to other methods of determining the molecular weight of viruses, sedimentation and diffusion, sedimentation equilibrium, light scattering, and electron microscopy counting, the method of quantitative electron microscopy is competitive. In some ways quantitative electron microscopy is superior to other methods for the determination of molecular weight: There is no limitation to the size of the virus, no experimental time involved and no concentration and purity of virus preparations required, and finally it is independent of the geometry of the virion. In one important aspect it is unique when compared to other methods; namely, it affords one the capacity to analyse individual virus particles."}
{"id": "PMID:189346", "title": "A possible mechanism for the action of some myxoviruses.", "content": "The redox properties of some myxoviruses [Fowl plaque virus strain Rostock (FPV), New Castle Disease virus strain Italy (NDV), B/Hong Kong, A/Port Chalmers, A/Victoria, A/Scotland, and A/Fort Dir) and electron microscopic studies as well as by the determination of the hemagglutination (HA) titer (antigen efficiency). The results have shown that viruses decrease the spin concentration of Cu2+ by acting as a reducing species (electron donor) which will result in the inactivation (oxidation) of the virus. Addition of an oxidizing substance, such as H2O2, to a virus suspension also leads to an oxidation of the viruses, and, thus, to their inability to reduce Cu2+. This result is confirmed by the decrease of the HA titer of viruses with increasing Cu2+ concentrations. H2O2 could not be applied for the HA titer test since it interacts with the erythrocytes of the chicken blood used for this determination. Therefore, another oxidizing substance (oxidized glutathione, GSS) was selected which exhibited a slightly less pronounced effect than Cu2+. Since reduced glutathione (GSH) exerts a similar but less pronounced effect than GSS, it might be concluded that viruses have a redox system of their own and act as reducing or oxidizing substance depending on the biological receptor system. Electron microscopic studies confirm this hypothesis. As can be seen by the electron micrographs, increasing concentrations of either Cu2+, GSS, H2O2, KMnO4, or GSH will, finally, result in a complete destruction of the virus. Because of structural similarities it might be assumed that other types of viruses behave very similarly.", "contents": "A possible mechanism for the action of some myxoviruses. The redox properties of some myxoviruses [Fowl plaque virus strain Rostock (FPV), New Castle Disease virus strain Italy (NDV), B/Hong Kong, A/Port Chalmers, A/Victoria, A/Scotland, and A/Fort Dir) and electron microscopic studies as well as by the determination of the hemagglutination (HA) titer (antigen efficiency). The results have shown that viruses decrease the spin concentration of Cu2+ by acting as a reducing species (electron donor) which will result in the inactivation (oxidation) of the virus. Addition of an oxidizing substance, such as H2O2, to a virus suspension also leads to an oxidation of the viruses, and, thus, to their inability to reduce Cu2+. This result is confirmed by the decrease of the HA titer of viruses with increasing Cu2+ concentrations. H2O2 could not be applied for the HA titer test since it interacts with the erythrocytes of the chicken blood used for this determination. Therefore, another oxidizing substance (oxidized glutathione, GSS) was selected which exhibited a slightly less pronounced effect than Cu2+. Since reduced glutathione (GSH) exerts a similar but less pronounced effect than GSS, it might be concluded that viruses have a redox system of their own and act as reducing or oxidizing substance depending on the biological receptor system. Electron microscopic studies confirm this hypothesis. As can be seen by the electron micrographs, increasing concentrations of either Cu2+, GSS, H2O2, KMnO4, or GSH will, finally, result in a complete destruction of the virus. Because of structural similarities it might be assumed that other types of viruses behave very similarly."}
{"id": "PMID:189347", "title": "ESR and optical absorption studies on the copper (II) interaction with aromatic amino acids.", "content": "Electron spin resonance and optical absorption studies have been done in order to investigate the interaction between Cu2+ and aromatic amino acids in aqueous solution at 77 K and at room temperature as well. Depending on the concentration each aromatic amino acid can form two different kinds of complexes with Cu2+ which can be characterized by its ESR pattern. Additional information was obtained from optical d-d and CT transitions.", "contents": "ESR and optical absorption studies on the copper (II) interaction with aromatic amino acids. Electron spin resonance and optical absorption studies have been done in order to investigate the interaction between Cu2+ and aromatic amino acids in aqueous solution at 77 K and at room temperature as well. Depending on the concentration each aromatic amino acid can form two different kinds of complexes with Cu2+ which can be characterized by its ESR pattern. Additional information was obtained from optical d-d and CT transitions."}
{"id": "PMID:189344", "title": "Effect of economic barriers to medical care on patients' noncompliance.", "content": "The post-hospital care of 290 patients with selected chronic conditions of a specific severity who were discharged over a 3-month period from a general hospital in Halifax, Canada, was studied. The majority of the patients were married. The average age of the men was 59.2 years and of the women 58.1. More than half of the patients belonged to the low socioeconomic group earning between $1,000 and $6,999 a year. Their average period of education was 8.4 years. Interviews with the patients about their compliance with physicians' orders revealed that 40.4 percent had not complied with one or more of their physician's recommendations. Lack of compliance was related to age, marital status, education, income, and severity of disease. It was also associated with high dosages of medicine and multiple prescriptions. Cost barriers constituted a significant factor in noncompliance.", "contents": "Effect of economic barriers to medical care on patients' noncompliance. The post-hospital care of 290 patients with selected chronic conditions of a specific severity who were discharged over a 3-month period from a general hospital in Halifax, Canada, was studied. The majority of the patients were married. The average age of the men was 59.2 years and of the women 58.1. More than half of the patients belonged to the low socioeconomic group earning between $1,000 and $6,999 a year. Their average period of education was 8.4 years. Interviews with the patients about their compliance with physicians' orders revealed that 40.4 percent had not complied with one or more of their physician's recommendations. Lack of compliance was related to age, marital status, education, income, and severity of disease. It was also associated with high dosages of medicine and multiple prescriptions. Cost barriers constituted a significant factor in noncompliance."}
{"id": "PMID:189351", "title": "Pancreatic calcifications in malignant islet cell tumors.", "content": "Of 623 cases of malignant pancreatic tumor seen at University of Chicago hospitals over the last 30 years, 23 cases of malignant islet cell tumor were found (8 additional cases were found in the literature). Calcification, found in 2 of these cases, was characteristically discrete and nodular (calcifications found in chronic pancreatitis are typically diffuse, multiple, and punctuate). At least 7 of the 10 cases of islet cell tumor with calcification were malignant. Slow growth of the tumor, with calcified metastases, strongly suggests the diagnosis of malignancy; this combination of findings has been established in 3 cases. In 73 cases of benign islet cell tumor, no calcifications were found.", "contents": "Pancreatic calcifications in malignant islet cell tumors. Of 623 cases of malignant pancreatic tumor seen at University of Chicago hospitals over the last 30 years, 23 cases of malignant islet cell tumor were found (8 additional cases were found in the literature). Calcification, found in 2 of these cases, was characteristically discrete and nodular (calcifications found in chronic pancreatitis are typically diffuse, multiple, and punctuate). At least 7 of the 10 cases of islet cell tumor with calcification were malignant. Slow growth of the tumor, with calcified metastases, strongly suggests the diagnosis of malignancy; this combination of findings has been established in 3 cases. In 73 cases of benign islet cell tumor, no calcifications were found."}
{"id": "PMID:189369", "title": "Cytologic and cytochemical behavior of primary malignant bone tumors.", "content": "Cytologic and cytochemical examination of eighteen cases of round-cell sarcoma of bone allowed classification of these tumors into four cytologic groups. Additional cytochemical examinations based on the PAS and D-PAS reactions, and the demonstration of the activity of peroxidase, naphtol-ASD-Chloracetate esterase, alpha-naphthylacetate esterase, naphthol-AS-acetate esterase with and without sodium fluoride inhibition, acid and alkaline phosphatases yielded no evidence of uniform behavior among the individual groups or within any single group. The studies showed that a positive glycogen reaction cannot be used as a basic criterion for the classification of such tumors as Ewing's sarcoma and for regarding them as a uniform tumor group. It is possible that a pool of tumors is involved, including tumors of monocytic and probably of lymphocytic origin, reticulum-cell sarcoma, tumors of myelocytic and erythroplastic origin, stem-cell tumors, and endothelial-cell tumors. Histologic examination alone is not sufficient for the classification of round-cell sarcomas of bone, and it should be supplemented by cytologic and cytochemical or histochemical methods. Osteosarcomas (23 cases) and chondrosarcomas (8 cases) display cells which are characteristic for these tumors and which could be correlated with their benign counterparts, osteoblasts and chondroid cells. The histologically recognizable degree of malignancy of chondrosarcoma can be evaluated better with the cytologic than with the histologic technic. Indications of the possibilities of differential diagnosis based on the cytologic pictures of benign and malignant osteoplastic and chondroplastic tumors, giant-cell tumors and chordoma are discussed.", "contents": "Cytologic and cytochemical behavior of primary malignant bone tumors. Cytologic and cytochemical examination of eighteen cases of round-cell sarcoma of bone allowed classification of these tumors into four cytologic groups. Additional cytochemical examinations based on the PAS and D-PAS reactions, and the demonstration of the activity of peroxidase, naphtol-ASD-Chloracetate esterase, alpha-naphthylacetate esterase, naphthol-AS-acetate esterase with and without sodium fluoride inhibition, acid and alkaline phosphatases yielded no evidence of uniform behavior among the individual groups or within any single group. The studies showed that a positive glycogen reaction cannot be used as a basic criterion for the classification of such tumors as Ewing's sarcoma and for regarding them as a uniform tumor group. It is possible that a pool of tumors is involved, including tumors of monocytic and probably of lymphocytic origin, reticulum-cell sarcoma, tumors of myelocytic and erythroplastic origin, stem-cell tumors, and endothelial-cell tumors. Histologic examination alone is not sufficient for the classification of round-cell sarcomas of bone, and it should be supplemented by cytologic and cytochemical or histochemical methods. Osteosarcomas (23 cases) and chondrosarcomas (8 cases) display cells which are characteristic for these tumors and which could be correlated with their benign counterparts, osteoblasts and chondroid cells. The histologically recognizable degree of malignancy of chondrosarcoma can be evaluated better with the cytologic than with the histologic technic. Indications of the possibilities of differential diagnosis based on the cytologic pictures of benign and malignant osteoplastic and chondroplastic tumors, giant-cell tumors and chordoma are discussed."}
{"id": "PMID:189370", "title": "Morphological, biological, immunological and biochemical studies on bone tumors of animals and man.", "content": "Biological studies on FBJ osteosarcoma virus in tissue cultures have led to the isolation of murine sarcoma virus. Characteristic type C-MuLV particles were observed in bone tumors induced by the SD-MSV-M-virus in vitro and in vivo. The SD-MSV-M virus also induced bone tumors in rats of all strains tested, and it has a similar tumor-inducing property in hamsters. Immunoelectronmicroscopic studies showed that envelope antigens of MSV-SD virus in rat bone tumors can be distinguished from those found in hamster bone tumor cells. In tissue cultures of MSV-SD rat bone tumors, two separate cell lines have been established: one of them releases both MSV and MuLV and the other produces MuL virus only. The MuLV in this cell line acts as helper. The different interactions appear to support the concept of control mechanisms for the partial expression of genes which are responsible for neoplastic properties, virus replication, and synthesis of gs-antigens. Biochemical studies on structural rearrangement and subunit composition of RNA released from MSV-SD virus, have shown that there are two forms of the native genome RNA differing in their sedimentation coeffiiecients and in subunit composition. In human osteosarcoma tissue culture, type-C viruslike particles are found. In cocultures derived from human osteosarcoma with cells taken from the bone marrow or peripheral blood of patients with different types of leukemia, certain morphological changes are observed which resemble those induced in  animal cells by RNA tumor viruses. In osteosarcomas where no cytoplasmic antigen could be proved by an immunofluorescence test, the antigen could be produced by cocultivation with antigen-positive leukemic bone marrow cells. Whole human embryo cells treated with fluid from leukemia bone marrow cultures showed the presence of the cytoplasmic antigen when tested with positive sera, but they showed no morphologic changes. In high molecular weight RNA species, sedimentation coefficients ranging from 62S to 68S are demonstrated by molecular hybridization techniques. In cross-hybridization experiments, annealing values were observed only with complementary DNA products synthesized from sarcoma viruses. Three particularly high molecular weight RNA species released from human sarcoma cell cultures showed no cross-hybridization with either the DNA product of Rauscher leukemia virus or that of Gross leukemia virus.", "contents": "Morphological, biological, immunological and biochemical studies on bone tumors of animals and man. Biological studies on FBJ osteosarcoma virus in tissue cultures have led to the isolation of murine sarcoma virus. Characteristic type C-MuLV particles were observed in bone tumors induced by the SD-MSV-M-virus in vitro and in vivo. The SD-MSV-M virus also induced bone tumors in rats of all strains tested, and it has a similar tumor-inducing property in hamsters. Immunoelectronmicroscopic studies showed that envelope antigens of MSV-SD virus in rat bone tumors can be distinguished from those found in hamster bone tumor cells. In tissue cultures of MSV-SD rat bone tumors, two separate cell lines have been established: one of them releases both MSV and MuLV and the other produces MuL virus only. The MuLV in this cell line acts as helper. The different interactions appear to support the concept of control mechanisms for the partial expression of genes which are responsible for neoplastic properties, virus replication, and synthesis of gs-antigens. Biochemical studies on structural rearrangement and subunit composition of RNA released from MSV-SD virus, have shown that there are two forms of the native genome RNA differing in their sedimentation coeffiiecients and in subunit composition. In human osteosarcoma tissue culture, type-C viruslike particles are found. In cocultures derived from human osteosarcoma with cells taken from the bone marrow or peripheral blood of patients with different types of leukemia, certain morphological changes are observed which resemble those induced in  animal cells by RNA tumor viruses. In osteosarcomas where no cytoplasmic antigen could be proved by an immunofluorescence test, the antigen could be produced by cocultivation with antigen-positive leukemic bone marrow cells. Whole human embryo cells treated with fluid from leukemia bone marrow cultures showed the presence of the cytoplasmic antigen when tested with positive sera, but they showed no morphologic changes. In high molecular weight RNA species, sedimentation coefficients ranging from 62S to 68S are demonstrated by molecular hybridization techniques. In cross-hybridization experiments, annealing values were observed only with complementary DNA products synthesized from sarcoma viruses. Three particularly high molecular weight RNA species released from human sarcoma cell cultures showed no cross-hybridization with either the DNA product of Rauscher leukemia virus or that of Gross leukemia virus."}
{"id": "PMID:189371", "title": "The endogenous origin and transmission of RNA viral genomes that code for cancer.", "content": "In certain experimental animals, type-C virus genomes are universally prevalent. They are mostly but not exclusively transmitted genetically and produce tumors naturally as well as when transmitted experimentally. The spontaneous virus and tumor expressions are regulated and modified by genetic factors; and virus-specific virogenes used as vaccines prior to high-level natural expressions can suppress natural expressions of the virogenes. Application of this significant information to the prevention of cancer in mice now seems quite feasible; however its application to the control of human cancer is still dependent on the isolation of specific human type-C virus(es).", "contents": "The endogenous origin and transmission of RNA viral genomes that code for cancer. In certain experimental animals, type-C virus genomes are universally prevalent. They are mostly but not exclusively transmitted genetically and produce tumors naturally as well as when transmitted experimentally. The spontaneous virus and tumor expressions are regulated and modified by genetic factors; and virus-specific virogenes used as vaccines prior to high-level natural expressions can suppress natural expressions of the virogenes. Application of this significant information to the prevention of cancer in mice now seems quite feasible; however its application to the control of human cancer is still dependent on the isolation of specific human type-C virus(es)."}
{"id": "PMID:189372", "title": "Pathogenesis of radiation and virus-induced bone tumors.", "content": "Bone cancer can be induced by radionuclides that localize in the skeleton. Histologically, these experimentally induced tumors resemble those found naturally in man; they range from densely ossified osteogenic sarcomas to osteolytic tumors with giant cells and only a small osteoid component. Fibrosarcomas and hemangiosarcomas also can occur in some species. It has not been possible to determine the dose in terms of absorbed energy necessary for bone-tumor induction because radionuclides are not deposited uniformly, and they diminish in amount with time. Also, the precise time when irreversible noeplastic change occurs is not known. With X-rays, however, 500 rads delivered to the endosteal surface of a mouse femur has been shown to cause osteogenic sarcoma. Bone tumors can be induced in mice by viruses. FBJ osteosarcoma virus and RFB osteoma virus were obtained from spontaneous tumors; FBR osteosarcoma virus came from a radiation-induced tumor. All three are RNA viruses with C-type particle morphology, and they are propagated by injecting cell-free extracts of virus-induced tumor. All three are RNA viruses with C-type particle morphology, and they are propagated by injecting cell-free extracts of virus-induced tumor into newborn mice. Interaction studies with bone-seeking radionuclides and these viruses have led to the hypothesis that radiation produces cancer by inactivating a viral inhibitor. There is also evidence of a bone tumor virus in the human disease. The injection of cell-free extracts of human bone cancer into newborn Syrian hamsters has induced a variety of mesenchymal tumors at a rate significantly higher than in the control hamsters. Sixty tumors of this type, including 20 osteosarcomas, 11 fibrosarcomas, and 9 osteomas, have been diagnosed so far in experimental animals; in control hamsters there has been only one, a fibrosarcoma. Immunofluorescence assays and cytotoxicity studies indicated that these hamster tumors carried a human antigen.", "contents": "Pathogenesis of radiation and virus-induced bone tumors. Bone cancer can be induced by radionuclides that localize in the skeleton. Histologically, these experimentally induced tumors resemble those found naturally in man; they range from densely ossified osteogenic sarcomas to osteolytic tumors with giant cells and only a small osteoid component. Fibrosarcomas and hemangiosarcomas also can occur in some species. It has not been possible to determine the dose in terms of absorbed energy necessary for bone-tumor induction because radionuclides are not deposited uniformly, and they diminish in amount with time. Also, the precise time when irreversible noeplastic change occurs is not known. With X-rays, however, 500 rads delivered to the endosteal surface of a mouse femur has been shown to cause osteogenic sarcoma. Bone tumors can be induced in mice by viruses. FBJ osteosarcoma virus and RFB osteoma virus were obtained from spontaneous tumors; FBR osteosarcoma virus came from a radiation-induced tumor. All three are RNA viruses with C-type particle morphology, and they are propagated by injecting cell-free extracts of virus-induced tumor. All three are RNA viruses with C-type particle morphology, and they are propagated by injecting cell-free extracts of virus-induced tumor into newborn mice. Interaction studies with bone-seeking radionuclides and these viruses have led to the hypothesis that radiation produces cancer by inactivating a viral inhibitor. There is also evidence of a bone tumor virus in the human disease. The injection of cell-free extracts of human bone cancer into newborn Syrian hamsters has induced a variety of mesenchymal tumors at a rate significantly higher than in the control hamsters. Sixty tumors of this type, including 20 osteosarcomas, 11 fibrosarcomas, and 9 osteomas, have been diagnosed so far in experimental animals; in control hamsters there has been only one, a fibrosarcoma. Immunofluorescence assays and cytotoxicity studies indicated that these hamster tumors carried a human antigen."}
{"id": "PMID:189382", "title": "Inhibition by somatostatin of secretin-stimulated pancreatic secretion in man: a study with pure pancreatic juice.", "content": "The action of somatostatin on compostition and flow rate of pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct was evaluated in 5 healthy volunteers. Synthetic secretin (0.06 CU/kg-h) was intravenously infused throughout the 80-min study. Bicarbonate concentrations in pancreatic juice achieved constant levels (117 +/- 3 muEq/ml) after 10 min, whereas a steady state of juice flow (7.3 +/- 1.4 ml/5 min) was attained after 15 min of secretin infusion. In the third 20-min period, cyclic somatostatic (5 mug/kg-h i.v.) was given, leading to a decrease in pancreatic flow rate by 47% after 10 min, and by 67% after 15 min of somatostatin administration. Alrady 5 min after the infusion of somatostatin had been discontinued, pancreatic flow rate gradually recovered; presomatostatin levels, however, were not reached within 20 min. Cyclic AMP varied roughly in accordance with bicarbonate concentrations, whereas the chloride concentrations were reciprocally related. Bicarbonate, sodium, potassium, protein, and cyclic GMP concentrations did not change substantially due to somatostatin.", "contents": "Inhibition by somatostatin of secretin-stimulated pancreatic secretion in man: a study with pure pancreatic juice. The action of somatostatin on compostition and flow rate of pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct was evaluated in 5 healthy volunteers. Synthetic secretin (0.06 CU/kg-h) was intravenously infused throughout the 80-min study. Bicarbonate concentrations in pancreatic juice achieved constant levels (117 +/- 3 muEq/ml) after 10 min, whereas a steady state of juice flow (7.3 +/- 1.4 ml/5 min) was attained after 15 min of secretin infusion. In the third 20-min period, cyclic somatostatic (5 mug/kg-h i.v.) was given, leading to a decrease in pancreatic flow rate by 47% after 10 min, and by 67% after 15 min of somatostatin administration. Alrady 5 min after the infusion of somatostatin had been discontinued, pancreatic flow rate gradually recovered; presomatostatin levels, however, were not reached within 20 min. Cyclic AMP varied roughly in accordance with bicarbonate concentrations, whereas the chloride concentrations were reciprocally related. Bicarbonate, sodium, potassium, protein, and cyclic GMP concentrations did not change substantially due to somatostatin."}
{"id": "PMID:189383", "title": "Virus antibody levels in IgA deficiency.", "content": "IgA-deficient blood donors and their age- and sex-matched controls were compared for the occurrence of complement-fixing antibodies in serum against several viruses. The level in the IgA-deficient persons was slightly higher against several respiratory pathogens (adenoviruses, type B influenza virus, parainfluenza virus, and respiratory syncytial virus) that give rise to localized infections, and against coxsackie B group of viruses. No corresponding difference was observed in mumps, varicella, and cytomegalovirus infections, where viraemia is a characteristic feature, or in Mycoplasma pneumoniae infection.", "contents": "Virus antibody levels in IgA deficiency. IgA-deficient blood donors and their age- and sex-matched controls were compared for the occurrence of complement-fixing antibodies in serum against several viruses. The level in the IgA-deficient persons was slightly higher against several respiratory pathogens (adenoviruses, type B influenza virus, parainfluenza virus, and respiratory syncytial virus) that give rise to localized infections, and against coxsackie B group of viruses. No corresponding difference was observed in mumps, varicella, and cytomegalovirus infections, where viraemia is a characteristic feature, or in Mycoplasma pneumoniae infection."}
{"id": "PMID:189384", "title": "A trial of an alpha-adrenoreceptor blocking drug (indoramin) in exercise-induced bronchoconstriction.", "content": "In 10 patients with exercise-induced asthma oral indoramin, an alpha adrenoreceptor blocking drug, was ineffective in preventing the post-exercise fall in peak expiratory flow rate (PEFR). The values of PEFR at rest increased after administration of indoramin, providing indirect evidence for the existence of alpha receptors in the bronchial smooth muscle of asthmatic subjects.", "contents": "A trial of an alpha-adrenoreceptor blocking drug (indoramin) in exercise-induced bronchoconstriction. In 10 patients with exercise-induced asthma oral indoramin, an alpha adrenoreceptor blocking drug, was ineffective in preventing the post-exercise fall in peak expiratory flow rate (PEFR). The values of PEFR at rest increased after administration of indoramin, providing indirect evidence for the existence of alpha receptors in the bronchial smooth muscle of asthmatic subjects."}
{"id": "PMID:189385", "title": "Tracheobronchial clearance and beta-adrenoceptor stimulation in patients with chronic bronchitis.", "content": "The effect of a beta-adrenoceptor stimulating agent, terbutaline, on mucociliary transport in the lungs was studied in 10 patients with chronic bronchitis. Mucociliary transport was studied by having the patients inhale 6mum teflon particles tagged with 99mTc and by external measurement of the radioactivity in the lungs in the supine position. Terbutaline 0.25 mg and vehicle respectively were given subcutaneously in a cross-over double-blind study. On the average, clearance was slow in the examinations where the patients were given vehicle. Terbutaline produced a marked increase in mucociliary transport in four patients, a smaller increase in one and no effect in the others. Three out of the four patients who showed a marked inrease in clearance had less ventilatory impairment than the other seven patients. This may indicate that the mucociliary transport mechanism is less severely damaged in relatively early stages of the disease than in later stages. On the average FEV1.0 deteriorated significantly during the clearance measurements when vehicle was given, but did not change significantly when terbutaline was given.", "contents": "Tracheobronchial clearance and beta-adrenoceptor stimulation in patients with chronic bronchitis. The effect of a beta-adrenoceptor stimulating agent, terbutaline, on mucociliary transport in the lungs was studied in 10 patients with chronic bronchitis. Mucociliary transport was studied by having the patients inhale 6mum teflon particles tagged with 99mTc and by external measurement of the radioactivity in the lungs in the supine position. Terbutaline 0.25 mg and vehicle respectively were given subcutaneously in a cross-over double-blind study. On the average, clearance was slow in the examinations where the patients were given vehicle. Terbutaline produced a marked increase in mucociliary transport in four patients, a smaller increase in one and no effect in the others. Three out of the four patients who showed a marked inrease in clearance had less ventilatory impairment than the other seven patients. This may indicate that the mucociliary transport mechanism is less severely damaged in relatively early stages of the disease than in later stages. On the average FEV1.0 deteriorated significantly during the clearance measurements when vehicle was given, but did not change significantly when terbutaline was given."}
{"id": "PMID:189386", "title": "Viral, mycoplasma and bacterial infections in nurses with symptoms of respiratory diseases.", "content": "A consecutive series of 282 nurses of the University Hospital, Groningen, with complaints of the nose and/or throat associated with coughing and/or hoarseness were examined between April 1965 and February 1968. The intent was to obtain information on the incidence of viral, mycoplasma and bacterial infections, and on the relationship of these infections in nurses with chronic nonspecific lung disease (CNSLD). The following results were obtained: 1. Virus infections caused by influenza virus (A, B, and C), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus and/or Mycoplasma pneumoniae were confirmed in 30% of the nurses examined; if influenza was excluded, this figure was 20%. 2. Rhinovirus infections were found more often than all the other virus infections together (if influenza was excluded). 3. Approximately 25% of the nurses had signs of CNSLD. 4. In the course of the virus infections, nine out of 14 nurses with a history of chronic obstructive lung disease showed symptoms of exacerbation or recurrence of a generalized bronchial obstruction. 5. There was no difference in the incidence of virus infections in the group of nurses with and without CNSLD. 6. There were more bacterial infections (without a confirmed virus infection) in the subjects with CNSLD than in those without CNSLD. 7. There were more combined viral/bacterial infections in the patients with CNSLD than in those without CNSLD. 8. Patients with influenza did not have more bacterial infections than patients with other virus infections. This is also true for patients with CNSLD and influenza when regarded separately. The patients without CNSLD tended to have more bacterial infections with influenza than with other viral infections, but the difference was not statistically significant.", "contents": "Viral, mycoplasma and bacterial infections in nurses with symptoms of respiratory diseases. A consecutive series of 282 nurses of the University Hospital, Groningen, with complaints of the nose and/or throat associated with coughing and/or hoarseness were examined between April 1965 and February 1968. The intent was to obtain information on the incidence of viral, mycoplasma and bacterial infections, and on the relationship of these infections in nurses with chronic nonspecific lung disease (CNSLD). The following results were obtained: 1. Virus infections caused by influenza virus (A, B, and C), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus and/or Mycoplasma pneumoniae were confirmed in 30% of the nurses examined; if influenza was excluded, this figure was 20%. 2. Rhinovirus infections were found more often than all the other virus infections together (if influenza was excluded). 3. Approximately 25% of the nurses had signs of CNSLD. 4. In the course of the virus infections, nine out of 14 nurses with a history of chronic obstructive lung disease showed symptoms of exacerbation or recurrence of a generalized bronchial obstruction. 5. There was no difference in the incidence of virus infections in the group of nurses with and without CNSLD. 6. There were more bacterial infections (without a confirmed virus infection) in the subjects with CNSLD than in those without CNSLD. 7. There were more combined viral/bacterial infections in the patients with CNSLD than in those without CNSLD. 8. Patients with influenza did not have more bacterial infections than patients with other virus infections. This is also true for patients with CNSLD and influenza when regarded separately. The patients without CNSLD tended to have more bacterial infections with influenza than with other viral infections, but the difference was not statistically significant."}
{"id": "PMID:189387", "title": "[Dynamics of plasma catecholamines and beta-adrenoreceptor functions. Use of a new radio-enzymatic micro-method].", "content": "The new method for simultaneous determination of noradrenaline (NA), adrenaline (A) and dopamine in 50 mul plasma has proved specific, sensitive and readily reproducible. In 6 healthy volunteers NA was 190 pg/ml and A 63 pg/ml in the supine position and rose during graded upright exercise to NA 819 pg/ml and A 161 pg/ml (150 watts; p less than 0.001 and less than 0.05 respectively). NA and A paralleled exercise tachycardia (r = 0.894; p less than 0.001) and renin stimulation (r = 0.620; p less than 0.001). 21 patients with essential hypertension exhibited relatively higher NA concentrations both at rest and during graded exercise (p less than 0.05 for both). Exercise-stimulated NA and A further rose following 0.15 mg/kg propranolol i.v. (p less than 0.01 and p less than 0.05 respectively). With increasing age and blood pressure, plasma catecholamine concentrations rise while the reactivity of heart rate and renin secretion decreases. Acute pharmacological blockade of beta-adrenoreceptors increases catecholamine overflow in similar fashion to the physiological dissociation of plasma catecholamines and adrenoceptor responsiveness.", "contents": "[Dynamics of plasma catecholamines and beta-adrenoreceptor functions. Use of a new radio-enzymatic micro-method]. The new method for simultaneous determination of noradrenaline (NA), adrenaline (A) and dopamine in 50 mul plasma has proved specific, sensitive and readily reproducible. In 6 healthy volunteers NA was 190 pg/ml and A 63 pg/ml in the supine position and rose during graded upright exercise to NA 819 pg/ml and A 161 pg/ml (150 watts; p less than 0.001 and less than 0.05 respectively). NA and A paralleled exercise tachycardia (r = 0.894; p less than 0.001) and renin stimulation (r = 0.620; p less than 0.001). 21 patients with essential hypertension exhibited relatively higher NA concentrations both at rest and during graded exercise (p less than 0.05 for both). Exercise-stimulated NA and A further rose following 0.15 mg/kg propranolol i.v. (p less than 0.01 and p less than 0.05 respectively). With increasing age and blood pressure, plasma catecholamine concentrations rise while the reactivity of heart rate and renin secretion decreases. Acute pharmacological blockade of beta-adrenoreceptors increases catecholamine overflow in similar fashion to the physiological dissociation of plasma catecholamines and adrenoceptor responsiveness."}
{"id": "PMID:189389", "title": "[Lung changes after organ transplantation].", "content": "The morphological pulmonary alterations in renal transplant recipients have been investigated in the light of 62 autopsies. Apart from the predominant pulmonary edema of septic, uremic or circulatory origin, pneumonic opportunistic infections were prominent. The most important agents proved to be bacteria, cytomegalovirus and fungi. In most cases, mixed infections were observed. At autopsy, pneumocystis carinii infections appeared to be of little importance. The pathology of the pulmonary changes reflects the reduced defense inevitably following on immunosuppressive medication, which in turn is indispensable for successful transplantation.", "contents": "[Lung changes after organ transplantation]. The morphological pulmonary alterations in renal transplant recipients have been investigated in the light of 62 autopsies. Apart from the predominant pulmonary edema of septic, uremic or circulatory origin, pneumonic opportunistic infections were prominent. The most important agents proved to be bacteria, cytomegalovirus and fungi. In most cases, mixed infections were observed. At autopsy, pneumocystis carinii infections appeared to be of little importance. The pathology of the pulmonary changes reflects the reduced defense inevitably following on immunosuppressive medication, which in turn is indispensable for successful transplantation."}
{"id": "PMID:189390", "title": "Presynaptic electrical coupling in Aplysia: effects on postsynaptic chemical transmission.", "content": "The large cholinergic interneuron L10 in the abdominal ganglion of Aplysia mediates both chemical and electrical synaptic transmission. The amplitudes of postsynaptic potentials produced by different branches of L10 are differentially affected when the electrically coupled neuron L20 is depolarized or hyperpolarized. Polarizations applied to L20 are transmitted to L10 branches by the \"presynaptic\"electrical synapse. Depolarization increases the amplitude of the postsynaptic potential, while hyperpolarization has the opposite effect. The differential effects occur because current supplied through the electrical synapse undergoes more electrotonic decrement for the distant branches than for branches closer to the electrical synapse. These findings indicate that the presynaptic electrically coupled neuron may have an integrative role in the modulation of chemical synaptic efficacy mediated by L10.", "contents": "Presynaptic electrical coupling in Aplysia: effects on postsynaptic chemical transmission. The large cholinergic interneuron L10 in the abdominal ganglion of Aplysia mediates both chemical and electrical synaptic transmission. The amplitudes of postsynaptic potentials produced by different branches of L10 are differentially affected when the electrically coupled neuron L20 is depolarized or hyperpolarized. Polarizations applied to L20 are transmitted to L10 branches by the \"presynaptic\"electrical synapse. Depolarization increases the amplitude of the postsynaptic potential, while hyperpolarization has the opposite effect. The differential effects occur because current supplied through the electrical synapse undergoes more electrotonic decrement for the distant branches than for branches closer to the electrical synapse. These findings indicate that the presynaptic electrically coupled neuron may have an integrative role in the modulation of chemical synaptic efficacy mediated by L10."}
{"id": "PMID:189397", "title": "[Colonic Crohn's disease: diagnostic and therapeutic problems. Apropos of 11 cases].", "content": "The authors report a few unusual cases of Crohn's disease of the colon and discuss the diagnostic problems which are raised in such cases. They then review the various colonic diseases liable to be considered in a differential diagnosis, and which may be linked to colonic Crohn's disease, e.g. ulcerative colitis, intestinal tuberculosis, carcinoma of the colon, colonic diverticulosis and sarcoidosis. In a chapter on treatment, they emphasize the favourable effect of acexamic acid and the necessity for very wide colonic resection, and they note a complication which they encountered during surgery for Crohn's disease: lymphatic peritonitis on the 8th day after right colectomy.", "contents": "[Colonic Crohn's disease: diagnostic and therapeutic problems. Apropos of 11 cases]. The authors report a few unusual cases of Crohn's disease of the colon and discuss the diagnostic problems which are raised in such cases. They then review the various colonic diseases liable to be considered in a differential diagnosis, and which may be linked to colonic Crohn's disease, e.g. ulcerative colitis, intestinal tuberculosis, carcinoma of the colon, colonic diverticulosis and sarcoidosis. In a chapter on treatment, they emphasize the favourable effect of acexamic acid and the necessity for very wide colonic resection, and they note a complication which they encountered during surgery for Crohn's disease: lymphatic peritonitis on the 8th day after right colectomy."}
{"id": "PMID:189398", "title": "[Lymphatic peritonitis occurring 8 days after right colectomy for Crohn's disease].", "content": "The authors have observed on two occasions, a diffuse peritoneal syndrome in the post-operative period after right hemi-colectomy for Crohn's disease, and interpret, in the absence of complications at the level of the anastomosis, as peritonitis due to septic lymphorrhea. According to them, it does not seem that this syndrome has the same significance as that described following appendicectomy in children.", "contents": "[Lymphatic peritonitis occurring 8 days after right colectomy for Crohn's disease]. The authors have observed on two occasions, a diffuse peritoneal syndrome in the post-operative period after right hemi-colectomy for Crohn's disease, and interpret, in the absence of complications at the level of the anastomosis, as peritonitis due to septic lymphorrhea. According to them, it does not seem that this syndrome has the same significance as that described following appendicectomy in children."}
{"id": "PMID:189422", "title": "[Bone-marrow biopsy in Hodgkin's disease].", "content": "In 349 subjects with Hodgkin's disease 520 bone marrow biopsies were carried out: 454 did not lead to the discovery of any tumour (87.5%), 66 permitted us to discover a tumour (12.5%). Among the bone marrows without Hodgkin tissue, the hematopoietic tissue was normal in 233 bone marrows (51.2%), hyperplastic in 157 bone marrows (34.7%), hypoplastic or aplastic in 64 bone marrows (14%). Eosinophilia was noted in 13% of cases, marked plasmacytosis was noted in 24%. Among the cases with a tumour, 89.2% showed a massive lesion; 10.7% showed partial lesions. The frequency of involvement was 5.4% for clinical stages I. 6.2% for stage II. 17.1% for stage III. 47.6% for stageIV. Bone marrow involvement at the start of the disease was found in 3% of cases, even in stages I and II. The involvements were especially frequent in the histological forms, stage III (19.4%) and IV (30.4%). In splenectomised patients, bone marrow involvement was 5 times more common when the spleen was also involved. 50 times more common when the liver was involved. The bone marrow which may be used to detect hematogenic spread of Hodgkin's disease is an investigation which should be carried out as a routine in the early stages of the disease and whenever a relapse is suspected.", "contents": "[Bone-marrow biopsy in Hodgkin's disease]. In 349 subjects with Hodgkin's disease 520 bone marrow biopsies were carried out: 454 did not lead to the discovery of any tumour (87.5%), 66 permitted us to discover a tumour (12.5%). Among the bone marrows without Hodgkin tissue, the hematopoietic tissue was normal in 233 bone marrows (51.2%), hyperplastic in 157 bone marrows (34.7%), hypoplastic or aplastic in 64 bone marrows (14%). Eosinophilia was noted in 13% of cases, marked plasmacytosis was noted in 24%. Among the cases with a tumour, 89.2% showed a massive lesion; 10.7% showed partial lesions. The frequency of involvement was 5.4% for clinical stages I. 6.2% for stage II. 17.1% for stage III. 47.6% for stageIV. Bone marrow involvement at the start of the disease was found in 3% of cases, even in stages I and II. The involvements were especially frequent in the histological forms, stage III (19.4%) and IV (30.4%). In splenectomised patients, bone marrow involvement was 5 times more common when the spleen was also involved. 50 times more common when the liver was involved. The bone marrow which may be used to detect hematogenic spread of Hodgkin's disease is an investigation which should be carried out as a routine in the early stages of the disease and whenever a relapse is suspected."}
{"id": "PMID:189423", "title": "[Morphological aspects of the bone marrow in hairy-cell leukemia].", "content": "Bone marrow plays a considerable role in the diagnosis of hairy cell leukemia. The morphological aspects should be well known. One should emphasize the existence of aplastic or hypoplastic forms requiring one to repeat biopsy on the slightest clinical suscpicon. Routine histological techniques are sufficient for the diagnosis. The ultrastructural study also provides valuable histological and cytological evidence.", "contents": "[Morphological aspects of the bone marrow in hairy-cell leukemia]. Bone marrow plays a considerable role in the diagnosis of hairy cell leukemia. The morphological aspects should be well known. One should emphasize the existence of aplastic or hypoplastic forms requiring one to repeat biopsy on the slightest clinical suscpicon. Routine histological techniques are sufficient for the diagnosis. The ultrastructural study also provides valuable histological and cytological evidence."}
{"id": "PMID:189424", "title": "[Bone-marrow biopsy in chronic myeloid leukemia. Value of the initial examination].", "content": "In 31 patients with chronic myeloid leukemia, the initial bone marrow biopsy constantly showed considerable cell richness. The maturation of the granulocytes was harmonious in 52% of cases, with a predominance of myelocytes in 32% of cases, and groups of myeloblasts in 13% of cases. Eosinophilia was frequent and fairly intense. Fairly numerous loaded cells and Charcot-Leyden crystals were signs of granulocyte failure in the bone marrow. The erythroblasts were reduced, the megakaryocytes increased. Myelofibrosis was present in 45% of cases. This gave a very characteristic histological appearance. It was not possible to draw up correlations between the type of granulocyte maturation and/or the presence of myelofibrosis and, on the other hand, the clinical course of the disease, but the small number of case studied both in our series and in the literature do not permit one to carry out a proper statistical study.", "contents": "[Bone-marrow biopsy in chronic myeloid leukemia. Value of the initial examination]. In 31 patients with chronic myeloid leukemia, the initial bone marrow biopsy constantly showed considerable cell richness. The maturation of the granulocytes was harmonious in 52% of cases, with a predominance of myelocytes in 32% of cases, and groups of myeloblasts in 13% of cases. Eosinophilia was frequent and fairly intense. Fairly numerous loaded cells and Charcot-Leyden crystals were signs of granulocyte failure in the bone marrow. The erythroblasts were reduced, the megakaryocytes increased. Myelofibrosis was present in 45% of cases. This gave a very characteristic histological appearance. It was not possible to draw up correlations between the type of granulocyte maturation and/or the presence of myelofibrosis and, on the other hand, the clinical course of the disease, but the small number of case studied both in our series and in the literature do not permit one to carry out a proper statistical study."}
{"id": "PMID:189425", "title": "[Bone-marrow biopsy in chronic myeloid leukemia. Significance during development].", "content": "In 29 patients bone marrow biopsy carried out during the course of chronic myeloid luekemia, permitted the authors to divide up the patients into 5 histologically different groups according to the association of 3 parameters: the richness in granulocytes, the state of the matrix, the degree of leukoblastosis. There was, in most cases, correspondence between the histological appearance and the clinical and laboratory symptoms. This was particularly clear when the patient entered the terminal phase of the disease. 4 of the 5 histological groups had an unfavourable short-term prognosis, i.e., granulocyte hyperplasia with myelofibrosis, aplasia with normal matrix or with myelofibrosis and massive leukoblast invasion.", "contents": "[Bone-marrow biopsy in chronic myeloid leukemia. Significance during development]. In 29 patients bone marrow biopsy carried out during the course of chronic myeloid luekemia, permitted the authors to divide up the patients into 5 histologically different groups according to the association of 3 parameters: the richness in granulocytes, the state of the matrix, the degree of leukoblastosis. There was, in most cases, correspondence between the histological appearance and the clinical and laboratory symptoms. This was particularly clear when the patient entered the terminal phase of the disease. 4 of the 5 histological groups had an unfavourable short-term prognosis, i.e., granulocyte hyperplasia with myelofibrosis, aplasia with normal matrix or with myelofibrosis and massive leukoblast invasion."}
{"id": "PMID:189428", "title": "[Extrinsic compression of the celiac trunk by the arcuate ligament of the diaphragm. Apropos of 5 cases].", "content": "The authors report 5 cases (3 women and 2 men) of extrinsic stenosis of the coeliac axis by the arcuate ligament of the diaphragm. In one of the latter, the stenosis of the coeliac axis was associated with chronic calcific pancreatitis. These 5 patients were operated on. Division of the arcuate ligament gave on the whole very favourable results. (3 excellent results, one good and one average result). The authors then recall the clinical, angiographic and pathogenic data in this disease which remains exceptional. The diagnosis should be made and operation decided only after a fairly long period of observation during which one has elimiatned the diagnoses of gastro-intestinal, gall bladder, pancreatic and above all psychiatric disease by endoscopy, radiography and symptomatic medical treatment.", "contents": "[Extrinsic compression of the celiac trunk by the arcuate ligament of the diaphragm. Apropos of 5 cases]. The authors report 5 cases (3 women and 2 men) of extrinsic stenosis of the coeliac axis by the arcuate ligament of the diaphragm. In one of the latter, the stenosis of the coeliac axis was associated with chronic calcific pancreatitis. These 5 patients were operated on. Division of the arcuate ligament gave on the whole very favourable results. (3 excellent results, one good and one average result). The authors then recall the clinical, angiographic and pathogenic data in this disease which remains exceptional. The diagnosis should be made and operation decided only after a fairly long period of observation during which one has elimiatned the diagnoses of gastro-intestinal, gall bladder, pancreatic and above all psychiatric disease by endoscopy, radiography and symptomatic medical treatment."}
{"id": "PMID:189429", "title": "[Encephalopathy due to organomercuric compounds].", "content": "A 27 year old agricultural worker presented about one month after treating cereal seeds with an alcoxyalkyl mercurial derivative, an encephalopathy with a confusional state, a cerebellar stato-kinetic syndrome, an intention tremor and grand mal epileptic fits. Treatment with dimercaprol produced a clinical improvement on the fourth day with a fall in blood mercury from 3.5 mug to 2.2 mug whilst urinary excretion of mercury remained low. A fortnight later the patient was completely cured. Although less common than collective poisoning by ingestion, organo-mercurial encephalopathies due to occupational exposure are a real danger although it is not known whether the relative rareness of published cases is due only to lack of observance of security rules or to individual sensitivity which might be due to increased absorption of mercury through the lungs or skin. This case shows that although alkyl mercurial derivatives are reputed to be the most dangerous, alcoxyalkyl derivatives may also cause encephalopathies. Also, as long as non-toxic substances remain unavailable for use in agriculture, one should emphasise the necessity of careful observance of the security rules during manipulation of these products.", "contents": "[Encephalopathy due to organomercuric compounds]. A 27 year old agricultural worker presented about one month after treating cereal seeds with an alcoxyalkyl mercurial derivative, an encephalopathy with a confusional state, a cerebellar stato-kinetic syndrome, an intention tremor and grand mal epileptic fits. Treatment with dimercaprol produced a clinical improvement on the fourth day with a fall in blood mercury from 3.5 mug to 2.2 mug whilst urinary excretion of mercury remained low. A fortnight later the patient was completely cured. Although less common than collective poisoning by ingestion, organo-mercurial encephalopathies due to occupational exposure are a real danger although it is not known whether the relative rareness of published cases is due only to lack of observance of security rules or to individual sensitivity which might be due to increased absorption of mercury through the lungs or skin. This case shows that although alkyl mercurial derivatives are reputed to be the most dangerous, alcoxyalkyl derivatives may also cause encephalopathies. Also, as long as non-toxic substances remain unavailable for use in agriculture, one should emphasise the necessity of careful observance of the security rules during manipulation of these products."}
{"id": "PMID:189430", "title": "[Intestinal lymphatic ligation and arteriosclerosis. M Servelle's operation].", "content": "The authors report good results obtained by ligature of the intestinal lymphatics (Servelle's operation) performed in 15 patients with arteriosclerosis and followed up 1,2 and 3 years after the operation. The indications for the operation in the surgical treatment of arteriosclerosis are discussed.", "contents": "[Intestinal lymphatic ligation and arteriosclerosis. M Servelle's operation]. The authors report good results obtained by ligature of the intestinal lymphatics (Servelle's operation) performed in 15 patients with arteriosclerosis and followed up 1,2 and 3 years after the operation. The indications for the operation in the surgical treatment of arteriosclerosis are discussed."}
{"id": "PMID:189431", "title": "[Pathogenic considerations in an association of systemic sclerodermia, Gougerot-Sj\u00f6gren syndrome and active chronic hepatitis].", "content": "The authors, report a case of scleroderma associated with Sjogren's syndrome and chronic active hepatitis, and propose a series of theories on the relationship between these 3 conditions. Each is successively considered as the cause of the two others through a cellular immune deficiency although the possibility of a chance association cannot be excluded.", "contents": "[Pathogenic considerations in an association of systemic sclerodermia, Gougerot-Sj\u00f6gren syndrome and active chronic hepatitis]. The authors, report a case of scleroderma associated with Sjogren's syndrome and chronic active hepatitis, and propose a series of theories on the relationship between these 3 conditions. Each is successively considered as the cause of the two others through a cellular immune deficiency although the possibility of a chance association cannot be excluded."}
{"id": "PMID:189434", "title": "[Current place of the Pneumococcus in infectious pathology].", "content": "This work regroups an important number of acute pneumococcal infections with septicemia, which recalls that these infections are of current importance, owing to their frequency and poor prognosis. Present diagnositc, clinical, radiological and bacteriological methods are discussed and criticised. An important, but not exclusive place, is reserved for routine blood culture. Finally, the authors discuss future prospects of acute pneumococcal infections, mainly diagnostic and prophylactic.", "contents": "[Current place of the Pneumococcus in infectious pathology]. This work regroups an important number of acute pneumococcal infections with septicemia, which recalls that these infections are of current importance, owing to their frequency and poor prognosis. Present diagnositc, clinical, radiological and bacteriological methods are discussed and criticised. An important, but not exclusive place, is reserved for routine blood culture. Finally, the authors discuss future prospects of acute pneumococcal infections, mainly diagnostic and prophylactic."}
{"id": "PMID:189435", "title": "[Hodgkin's disease: study of delayed hypersensitivity of 64 non treated patients. Value of epicutaneous test using croton oil].", "content": "Cellular immunity in 64 patients with Hodgkin's disease was studied during diagnosis before any treatment. The functional deficiency of the thymodependent lymphocyte was demonstrated in vivo by skin tests and, in vitro, by the test of inhibition of leucocyte migration to phytohemagglutininin and spontaneous rosette formation, to sheep red cells. This deficiency correlates with the clinical spread and the histological severity. The relationship between skin anergy and biological tests was found. The epicutaneous test using croton oil possesses non-specific inflammatory activity. It is negative this test is negative, skin reactivity to specific antigens is reduced. The croton tests help interpretation of skin responses to specific antigens and thus assessment of the immune state.", "contents": "[Hodgkin's disease: study of delayed hypersensitivity of 64 non treated patients. Value of epicutaneous test using croton oil]. Cellular immunity in 64 patients with Hodgkin's disease was studied during diagnosis before any treatment. The functional deficiency of the thymodependent lymphocyte was demonstrated in vivo by skin tests and, in vitro, by the test of inhibition of leucocyte migration to phytohemagglutininin and spontaneous rosette formation, to sheep red cells. This deficiency correlates with the clinical spread and the histological severity. The relationship between skin anergy and biological tests was found. The epicutaneous test using croton oil possesses non-specific inflammatory activity. It is negative this test is negative, skin reactivity to specific antigens is reduced. The croton tests help interpretation of skin responses to specific antigens and thus assessment of the immune state."}
{"id": "PMID:189436", "title": "[Endocrine aspects of Steinert's disease].", "content": "The authors report a case of Steinert's disease in a woman and discuss the endocrine profile of this disease after giving an account of the criteria of diagnosis. Disorders of gonad function are mild in women, primary testicular atrophy is very frequent in man with reduction in 17-ketosteroids and testosterone. Thyroid function was normal but, in a few cases, a low fixation curve was found (our case) corrected by TSH stimulation. The frequency of cataract emphasizes the interest of this sign for detection. Diabetes, associated with hyperinsulinism, seemed more frequent than in a population without Steinert's disease. The pathogenesis of these endocrine disorders appears secondary and is ill explained if one considers it as a single disease. Better knowledge, no doubt linked to progress in biochemistry of normal and myopathic muscle, will help to explain the pathogenesis.", "contents": "[Endocrine aspects of Steinert's disease]. The authors report a case of Steinert's disease in a woman and discuss the endocrine profile of this disease after giving an account of the criteria of diagnosis. Disorders of gonad function are mild in women, primary testicular atrophy is very frequent in man with reduction in 17-ketosteroids and testosterone. Thyroid function was normal but, in a few cases, a low fixation curve was found (our case) corrected by TSH stimulation. The frequency of cataract emphasizes the interest of this sign for detection. Diabetes, associated with hyperinsulinism, seemed more frequent than in a population without Steinert's disease. The pathogenesis of these endocrine disorders appears secondary and is ill explained if one considers it as a single disease. Better knowledge, no doubt linked to progress in biochemistry of normal and myopathic muscle, will help to explain the pathogenesis."}
{"id": "PMID:189439", "title": "Myocardial infarct imaging with technetium-99m phosphates.", "content": "Technetium-99m-phosphate imaging is particularly valuable in detecting (1) small transmural infarcts (3 g and larger in size); (2) new acute transmural infarcts in or near regions of old infarction; (3) acute subendocardial infarcts (larger than 3 g in size); (4) acute infarction in patients with left bundle branch block; and (5) perioperative myocardial infarction. Localization of inferior and posterior myocardial infarction is improved with imaging. Sizing of acute anterior and lateral infarcts has been accurately done in dogs and should prove helpful in patients. Extensive evaluation in both experimental animals and in patients has shown 99mTc-phosphate myocardial imaging to be a useful clinical tool, and it may be one of the most sensitive noninvasive ways presently available to identify acute myocardial necrosis. It is important to understand that 99mTc-phosphate imaging has a different pathophysiology basis from EKG's or serum enzymes. These tests do not compete but instead should complement one another.", "contents": "Myocardial infarct imaging with technetium-99m phosphates. Technetium-99m-phosphate imaging is particularly valuable in detecting (1) small transmural infarcts (3 g and larger in size); (2) new acute transmural infarcts in or near regions of old infarction; (3) acute subendocardial infarcts (larger than 3 g in size); (4) acute infarction in patients with left bundle branch block; and (5) perioperative myocardial infarction. Localization of inferior and posterior myocardial infarction is improved with imaging. Sizing of acute anterior and lateral infarcts has been accurately done in dogs and should prove helpful in patients. Extensive evaluation in both experimental animals and in patients has shown 99mTc-phosphate myocardial imaging to be a useful clinical tool, and it may be one of the most sensitive noninvasive ways presently available to identify acute myocardial necrosis. It is important to understand that 99mTc-phosphate imaging has a different pathophysiology basis from EKG's or serum enzymes. These tests do not compete but instead should complement one another."}
{"id": "PMID:189440", "title": "Myocardial infarct imaging with technetium-labeled complexes.", "content": "Detection of acute myocardial infarction as an area of increased activity has intrigued investigators for some time. Initial attempts with 203Hg-chlormerodrin and 203Hg-fluorescein analogues were successful in man. More recently, however, successful imaging of the acute myocardial infarct has been achieved with several 99mTc complexes. A large group of radiotracers localize in acutely damaged tissue in various models of experimental infarction. From these data, a number of specific structural properties associated with infarct avidity have been identified; these include the presence of mercury and the structural configuration of the organic carrier.", "contents": "Myocardial infarct imaging with technetium-labeled complexes. Detection of acute myocardial infarction as an area of increased activity has intrigued investigators for some time. Initial attempts with 203Hg-chlormerodrin and 203Hg-fluorescein analogues were successful in man. More recently, however, successful imaging of the acute myocardial infarct has been achieved with several 99mTc complexes. A large group of radiotracers localize in acutely damaged tissue in various models of experimental infarction. From these data, a number of specific structural properties associated with infarct avidity have been identified; these include the presence of mercury and the structural configuration of the organic carrier."}
{"id": "PMID:189441", "title": "Rationale and radiopharmaceuticals for myocardial imaging.", "content": "Static radionuclide imaging procedures are now available for evaluating regional myocardial perfusion and for detecting acute myocardial infarction. Thallium-201, a radiopharmaceutical that possesses many of the characteristics of potassium analogues, at present is receiving the greatest attention as a regional blood flow indicator. Ischemic lesions appear as areas of decreased tracer uptake. Unfortunately, this agent is expensive, is in limited supply, and has a photopeak that is low for optimum imaging. Positive infarct images can be obtained with various Technetium-99m chelates. Pyrophosphate appears to be the best of the technetium compounds studied to date, although the mechanism of uptake of the chelates has not yet been fully elucidated. Therefore, quantitative measurements of infract size are not justified. As perfusion imaging and infarct imaging provide useful, complementary data, a dual tracer approach to evaluating patients with suspected coronary artery disease and/or myocardial infarction, is probably justifiable.", "contents": "Rationale and radiopharmaceuticals for myocardial imaging. Static radionuclide imaging procedures are now available for evaluating regional myocardial perfusion and for detecting acute myocardial infarction. Thallium-201, a radiopharmaceutical that possesses many of the characteristics of potassium analogues, at present is receiving the greatest attention as a regional blood flow indicator. Ischemic lesions appear as areas of decreased tracer uptake. Unfortunately, this agent is expensive, is in limited supply, and has a photopeak that is low for optimum imaging. Positive infarct images can be obtained with various Technetium-99m chelates. Pyrophosphate appears to be the best of the technetium compounds studied to date, although the mechanism of uptake of the chelates has not yet been fully elucidated. Therefore, quantitative measurements of infract size are not justified. As perfusion imaging and infarct imaging provide useful, complementary data, a dual tracer approach to evaluating patients with suspected coronary artery disease and/or myocardial infarction, is probably justifiable."}
{"id": "PMID:189446", "title": "The effects of carbohydrate, fat and total energy adjustment of Fredrickson's type IIb hyperlipoproteinaemia.", "content": "Fifteen patients with Fredrickson's type IIb hyperlipoproteinaemia were subjected to a 10-week dietary study during which time qualitative and quantitative alterations were carried out on the fat, carbohydrate and energy content of the diet. Significant reduction was observed in fasting serum cholesterol and triglyceride levels on substitution of polyunsaturated for saturated fat, and on total fat restriction. No changes in cholesterol and triglyceride levels were observed when dietary sucrose was replaced with complex carbohydrate, or when there was total carbohydrate restriction. The possible practical applications of these observations are discussed.", "contents": "The effects of carbohydrate, fat and total energy adjustment of Fredrickson's type IIb hyperlipoproteinaemia. Fifteen patients with Fredrickson's type IIb hyperlipoproteinaemia were subjected to a 10-week dietary study during which time qualitative and quantitative alterations were carried out on the fat, carbohydrate and energy content of the diet. Significant reduction was observed in fasting serum cholesterol and triglyceride levels on substitution of polyunsaturated for saturated fat, and on total fat restriction. No changes in cholesterol and triglyceride levels were observed when dietary sucrose was replaced with complex carbohydrate, or when there was total carbohydrate restriction. The possible practical applications of these observations are discussed."}
{"id": "PMID:189447", "title": "Adenocarcinoma of the urinary bladder. Histochemical distinction between urachal and metastatic carcinomas.", "content": "The mucopolysaccharide production of urachal and metastatic adenocarcinomas in the urinary bladder has been investigated. It is shown that urachal carcinomas do not produce sulphated acid mucopolysaccharides, whereas the metastases from the large bowel do. Since colonic carcinomas constitute the metastatic adenocarcinomas most common to the bladder, this histochemical difference is regarded as a useful distinguishing feature.", "contents": "Adenocarcinoma of the urinary bladder. Histochemical distinction between urachal and metastatic carcinomas. The mucopolysaccharide production of urachal and metastatic adenocarcinomas in the urinary bladder has been investigated. It is shown that urachal carcinomas do not produce sulphated acid mucopolysaccharides, whereas the metastases from the large bowel do. Since colonic carcinomas constitute the metastatic adenocarcinomas most common to the bladder, this histochemical difference is regarded as a useful distinguishing feature."}
{"id": "PMID:189450", "title": "Cytomegalovirus-induced haemolytic anaemia after cardiac surgery.", "content": "A patient, who underwent aortic valve replacement, developed a transient, autoimmune haemolytic anaemia in association with a significant rise in titre of antibodies against cytomegalovirus. A serological survey of blood donors indicated that the source of infection was fresh blood transfused during and shortly after surgery. A number of cases of short-lived haemolytic anaemia after large volume blood transfusion with cardiac surgery may be explained by this mechanism. It may be preferable  to use only blood that has been screened for evidence of recent cytomegalovirus infection if post-perfusion complications of this disease are to be avoided.", "contents": "Cytomegalovirus-induced haemolytic anaemia after cardiac surgery. A patient, who underwent aortic valve replacement, developed a transient, autoimmune haemolytic anaemia in association with a significant rise in titre of antibodies against cytomegalovirus. A serological survey of blood donors indicated that the source of infection was fresh blood transfused during and shortly after surgery. A number of cases of short-lived haemolytic anaemia after large volume blood transfusion with cardiac surgery may be explained by this mechanism. It may be preferable  to use only blood that has been screened for evidence of recent cytomegalovirus infection if post-perfusion complications of this disease are to be avoided."}
{"id": "PMID:189453", "title": "A comparative study of the neutralisation test and the indirect fluorescent antibody technique for the detection of antibodies to the virus of Aujeszky in pig sera.", "content": "A microneutralisation test and an indirect fluorescent antibody technique for the detection of antibodies to Aujeszky-virus in pig sera are described. All the sera were tested with both techniques and the results were compared. Serum dilutions of less than 1:32 which produced a positive reaction in the indirect FAT were considered nonspecific. Bij contrast, all neutralising antibody titers of less than 1:8 gave nonspecific reactions in the indirect FAT.", "contents": "A comparative study of the neutralisation test and the indirect fluorescent antibody technique for the detection of antibodies to the virus of Aujeszky in pig sera. A microneutralisation test and an indirect fluorescent antibody technique for the detection of antibodies to Aujeszky-virus in pig sera are described. All the sera were tested with both techniques and the results were compared. Serum dilutions of less than 1:32 which produced a positive reaction in the indirect FAT were considered nonspecific. Bij contrast, all neutralising antibody titers of less than 1:8 gave nonspecific reactions in the indirect FAT."}
{"id": "PMID:189454", "title": "[The presence of antibodies to IBR/IPV virus in cattle in the environs of Leyden (author's transl)].", "content": "The appearance of IBR among cattle in the environs of Leyden is reported. Possible explanations of local differences in the incidence of IBR and possible effects on IBR immunisation of cattle in these areas are referred to in the discussion.", "contents": "[The presence of antibodies to IBR/IPV virus in cattle in the environs of Leyden (author's transl)]. The appearance of IBR among cattle in the environs of Leyden is reported. Possible explanations of local differences in the incidence of IBR and possible effects on IBR immunisation of cattle in these areas are referred to in the discussion."}
{"id": "PMID:189455", "title": "[Methods for the control of avian tumour virus diseases (author's transl)].", "content": "Methods developed in the Netherlands for the control of avian tumour virus diseases, Marek's disease and lymphoid leukosis, are discussed. Marek's disease is successfully kept under control by vaccination of all day-old chickens raised for egg production. Broilers are not vaccinated. During 1975 over 23 million chicks were vaccinated with cell-associated Marek's disease virus CVI 988 vaccines and about 3 million doses of HVT vaccine were administered, mostly in lyophilised form. The mechanism of the immunity conferred by the MD vaccines is discussed. Lymphoid leukosis was successfully controlled in three inbred lines of White Leghorn chickens and in a commercial grand parent flock of White Plymouth Rocks. The control method that can be applied to flocks in the field is based on three elements: From an infected flock hens are selected in whose eggs no lymphoid leukosis viruses can be detected in pooled extracts of groups of embryos. Only eggs from hens that demonstrably do not shed virus congenitally to their embryos are used for the production of progeny. The offspring are reared in isolation until two months of age at which time the age related resistance against tumour formation appears to be sufficiently developed. The chickens are subsequently inoculated intramuscularly with lymphoid leukosis viruses of subgroups A and B and transferred to a conventional chicken house. The inoculated birds become persistently viremic, resist intramuscular challenge infections or exposure by contact, but produce virus-negative eggs during the laying period. For lymphoid leukosis, congenital infection is considered the usual mode of virus transmission. Horizontal virus transmission becomes important when virus-free chickens, reared in isolation for two months, are exposed in field conditions without previous \"vaccination\". During the egg-laying period of these flocks, virus shedding was observed in a similar percentage as in flocks with congenitally infected birds.", "contents": "[Methods for the control of avian tumour virus diseases (author's transl)]. Methods developed in the Netherlands for the control of avian tumour virus diseases, Marek's disease and lymphoid leukosis, are discussed. Marek's disease is successfully kept under control by vaccination of all day-old chickens raised for egg production. Broilers are not vaccinated. During 1975 over 23 million chicks were vaccinated with cell-associated Marek's disease virus CVI 988 vaccines and about 3 million doses of HVT vaccine were administered, mostly in lyophilised form. The mechanism of the immunity conferred by the MD vaccines is discussed. Lymphoid leukosis was successfully controlled in three inbred lines of White Leghorn chickens and in a commercial grand parent flock of White Plymouth Rocks. The control method that can be applied to flocks in the field is based on three elements: From an infected flock hens are selected in whose eggs no lymphoid leukosis viruses can be detected in pooled extracts of groups of embryos. Only eggs from hens that demonstrably do not shed virus congenitally to their embryos are used for the production of progeny. The offspring are reared in isolation until two months of age at which time the age related resistance against tumour formation appears to be sufficiently developed. The chickens are subsequently inoculated intramuscularly with lymphoid leukosis viruses of subgroups A and B and transferred to a conventional chicken house. The inoculated birds become persistently viremic, resist intramuscular challenge infections or exposure by contact, but produce virus-negative eggs during the laying period. For lymphoid leukosis, congenital infection is considered the usual mode of virus transmission. Horizontal virus transmission becomes important when virus-free chickens, reared in isolation for two months, are exposed in field conditions without previous \"vaccination\". During the egg-laying period of these flocks, virus shedding was observed in a similar percentage as in flocks with congenitally infected birds."}
{"id": "PMID:189457", "title": "An epidemic of acute hemorrhagic conjunctivitis in Sendai area, 1973-1974.", "content": "In 1973 and 1974, an epidemic of acute hemorrhagic conjunctivitis (AHC) with a tendency of less frequent conjunctival hemorrhage occurred among the staff of the National Railways and their family in Sendai area. Four strains of AHC virus and 4 strains, 1 of type 7 and 3 of type 8, of adenoviruses were isolated from 22 conjunctival swabs of the patients. Thirty-six (66%) out of 55 cases examined were proved serologically to be of AHC virus infection, and 7 cases (13%) were of adenovirus infection. Clinically, infrequent association of hemorrhagic conjunctivitis was most remarkable. Only 10 cases (28%) had detectable signs of hemorrhagic conjunctivitis. There were no substantial changes in antigenicity and optimum temperature for virus multiplication between prototype and isolated strains. The isolated strains, however, seemed to be less neutralizable and less producible at 29 degrees C than prototype strain.", "contents": "An epidemic of acute hemorrhagic conjunctivitis in Sendai area, 1973-1974. In 1973 and 1974, an epidemic of acute hemorrhagic conjunctivitis (AHC) with a tendency of less frequent conjunctival hemorrhage occurred among the staff of the National Railways and their family in Sendai area. Four strains of AHC virus and 4 strains, 1 of type 7 and 3 of type 8, of adenoviruses were isolated from 22 conjunctival swabs of the patients. Thirty-six (66%) out of 55 cases examined were proved serologically to be of AHC virus infection, and 7 cases (13%) were of adenovirus infection. Clinically, infrequent association of hemorrhagic conjunctivitis was most remarkable. Only 10 cases (28%) had detectable signs of hemorrhagic conjunctivitis. There were no substantial changes in antigenicity and optimum temperature for virus multiplication between prototype and isolated strains. The isolated strains, however, seemed to be less neutralizable and less producible at 29 degrees C than prototype strain."}
{"id": "PMID:189462", "title": "Thyroid uptake or radiophosphorus as influenced by thiourea parathormone, and ACTH in Heteropneustes fossilis.", "content": "The Indian catfish, Heteropneusted fossilis, was chemically thyroidectomized with thiourea. The uptake of radioactive phosphorus by the thyroid of these thyroidectomized fished was then studied. The effect of mammalian ACTH and parathormone on the thyroid uptake of P-32 by the treated fish was also studied. It was found that thiourea reduces the P-32 uptake considerably, whereas both the hormones, separately, elevate the P-32 levels in the thyroid to near control values.", "contents": "Thyroid uptake or radiophosphorus as influenced by thiourea parathormone, and ACTH in Heteropneustes fossilis. The Indian catfish, Heteropneusted fossilis, was chemically thyroidectomized with thiourea. The uptake of radioactive phosphorus by the thyroid of these thyroidectomized fished was then studied. The effect of mammalian ACTH and parathormone on the thyroid uptake of P-32 by the treated fish was also studied. It was found that thiourea reduces the P-32 uptake considerably, whereas both the hormones, separately, elevate the P-32 levels in the thyroid to near control values."}
{"id": "PMID:189463", "title": "Splanchnic and intestinal uptake and formation of estriol and estriol conjugates in the dog in vivo.", "content": "A loading dose of 3H-estriol was given to male dogs followed by a constant infusion. The concentrations of total radioactivity, conjugated estriol metabolites, estriol, estriol-o-glucosiduronate, estriol-16alpha-glucosiduronate, estriol-3-sulfate and estriol-3-sulfate, 16alpha-glucosiduronate were determined in plasma from the femoral artery(A), hepatic vein(HV) and superior mesenteric vein (SMV). From these values the splanchnic (100[1-HV/A]) and intestinal (100[1-SMV/A]) extractions were calculated. The mean splanchnic extraction of total radioactivity was positive (23, SE 3, P less than .01), indicating net uptake by the splanchnic area, possibly due to biliary excretion. The mean splanchnic extraction of estriol was 77, SE 1, P less than .01, also indicating net uptake. The splachnic extractions of estriol-3-glucosiduronate, estriol-16alpha-glucosiduronate and estriol-3-sulfate were negative (-15, SE 3, P less than .01; -23, SE 6, P less than .01; -31, SE 8, P less than .01 respectively) indicating net formation of these conjugates for release into the systemic circulation. The mean intestinal extraction of estriol was 12, SE 4, P less than .01, indicating net uptake by the intestine. This net uptake was associated with mean negative intestinal extractions of estriol-3-glucosiduronate (-15, SE 7, P approximately .05), estriol-3-sulfate (-33, SE 10, P less than .01) and estriol-3-sulfate, 16alpha-glucosiduronate (-53, SE 13, P less than .01), indicating net formation of these conjugates by the intestine.", "contents": "Splanchnic and intestinal uptake and formation of estriol and estriol conjugates in the dog in vivo. A loading dose of 3H-estriol was given to male dogs followed by a constant infusion. The concentrations of total radioactivity, conjugated estriol metabolites, estriol, estriol-o-glucosiduronate, estriol-16alpha-glucosiduronate, estriol-3-sulfate and estriol-3-sulfate, 16alpha-glucosiduronate were determined in plasma from the femoral artery(A), hepatic vein(HV) and superior mesenteric vein (SMV). From these values the splanchnic (100[1-HV/A]) and intestinal (100[1-SMV/A]) extractions were calculated. The mean splanchnic extraction of total radioactivity was positive (23, SE 3, P less than .01), indicating net uptake by the splanchnic area, possibly due to biliary excretion. The mean splanchnic extraction of estriol was 77, SE 1, P less than .01, also indicating net uptake. The splachnic extractions of estriol-3-glucosiduronate, estriol-16alpha-glucosiduronate and estriol-3-sulfate were negative (-15, SE 3, P less than .01; -23, SE 6, P less than .01; -31, SE 8, P less than .01 respectively) indicating net formation of these conjugates for release into the systemic circulation. The mean intestinal extraction of estriol was 12, SE 4, P less than .01, indicating net uptake by the intestine. This net uptake was associated with mean negative intestinal extractions of estriol-3-glucosiduronate (-15, SE 7, P approximately .05), estriol-3-sulfate (-33, SE 10, P less than .01) and estriol-3-sulfate, 16alpha-glucosiduronate (-53, SE 13, P less than .01), indicating net formation of these conjugates by the intestine."}
{"id": "PMID:189464", "title": "Cholecalciferol metabolites binding in porcine parathyroid glands.", "content": "We studied the cytoplasmic and nuclear binding of 25-hydroxychole-calciferol and 1alpha,25-dihydroxycholecalciferol inside porcine parathyroid glands. Both sterols bind to cytoplasmic components, but a specific nuclear uptake was demonstrated only for 1alpha,25-dihydroxycholecalciferol. These findings support the hypothesis that mammalian parathyroid glands are a target organ for some cholecalciferol metabolites.", "contents": "Cholecalciferol metabolites binding in porcine parathyroid glands. We studied the cytoplasmic and nuclear binding of 25-hydroxychole-calciferol and 1alpha,25-dihydroxycholecalciferol inside porcine parathyroid glands. Both sterols bind to cytoplasmic components, but a specific nuclear uptake was demonstrated only for 1alpha,25-dihydroxycholecalciferol. These findings support the hypothesis that mammalian parathyroid glands are a target organ for some cholecalciferol metabolites."}
{"id": "PMID:189465", "title": "A radioimmunoassay for corticosterone and its application to the measurement of stress in poultry.", "content": "A radioimmunoassay for corticosterone was developed using an antibody to corticosterone-21-hemisuccinate:bovine serum albumin. The assay possessed good specificity, sensitivity and reproducibility and required minimal sample preparation. Tests of adrenal function showed that stimulation of the adrenal with exogenous ACTH and with dexamethasone caused an increase and decrease, respectively, in plasma concentrations of corticosterone. Exposure to cold environmental temperatures caused an increase in plasma corticosterone. Handling and the removal of blood samples by venepuncture had no effect upon the concentration of corticosterone. It was concluded that this assay would accurately measure the response to stresses which affect the pituitary-adrenal axis.", "contents": "A radioimmunoassay for corticosterone and its application to the measurement of stress in poultry. A radioimmunoassay for corticosterone was developed using an antibody to corticosterone-21-hemisuccinate:bovine serum albumin. The assay possessed good specificity, sensitivity and reproducibility and required minimal sample preparation. Tests of adrenal function showed that stimulation of the adrenal with exogenous ACTH and with dexamethasone caused an increase and decrease, respectively, in plasma concentrations of corticosterone. Exposure to cold environmental temperatures caused an increase in plasma corticosterone. Handling and the removal of blood samples by venepuncture had no effect upon the concentration of corticosterone. It was concluded that this assay would accurately measure the response to stresses which affect the pituitary-adrenal axis."}
{"id": "PMID:189466", "title": "Effect of hypophysectomy on estrogen conjugation and on plasma and tissue concentrations of tritium after administration of 3H-estradiol-17beta.", "content": "Estradiol-17beta-6,7-3H was injected into ovariectomized (control) and ovariectomized, hypophysectomized (hypox) rats in order to study the binding of estradiol in the brain. Hypophysectomy resulted in a significant increase in the concentration of tritium in the hypothalamus, and preoptic area, as well as cortex, muscle, plasma and liver. However, since the liver was lighter in hypox rats, the total tritium content in the liver was unchanged from controls. Part of the weight reduction in the liver was due to a loss of stainable glycogen, which took place within 24 hours of hypox. The increase in circulating tritiated estradiol after hypox led us to investigate hepatic metabolism of estradiol. In vitro studies on liver slices from control and hypox rats demonstrated a significant reduction in the formation of conjugates of estrogen. Specifically, estradiol glucuronide and estrone sulfate formation were reduced in hypox rats and conversely the unmetabolized estradiol concentration was higher. Hypophysectomy for 24 hours results in a significant decrease in hepatic metabolism of estradiol-17beta.", "contents": "Effect of hypophysectomy on estrogen conjugation and on plasma and tissue concentrations of tritium after administration of 3H-estradiol-17beta. Estradiol-17beta-6,7-3H was injected into ovariectomized (control) and ovariectomized, hypophysectomized (hypox) rats in order to study the binding of estradiol in the brain. Hypophysectomy resulted in a significant increase in the concentration of tritium in the hypothalamus, and preoptic area, as well as cortex, muscle, plasma and liver. However, since the liver was lighter in hypox rats, the total tritium content in the liver was unchanged from controls. Part of the weight reduction in the liver was due to a loss of stainable glycogen, which took place within 24 hours of hypox. The increase in circulating tritiated estradiol after hypox led us to investigate hepatic metabolism of estradiol. In vitro studies on liver slices from control and hypox rats demonstrated a significant reduction in the formation of conjugates of estrogen. Specifically, estradiol glucuronide and estrone sulfate formation were reduced in hypox rats and conversely the unmetabolized estradiol concentration was higher. Hypophysectomy for 24 hours results in a significant decrease in hepatic metabolism of estradiol-17beta."}
{"id": "PMID:189467", "title": "Excretion of non-conjugated androstenedione and testosterone in human urine.", "content": "A method for the measurement of unconjugated testosterone and androstenedione in human urine is described. The method uses chromatographic separation followed by radioimmunoassay and has been examined for reliability. The mean 24-hour excretion of androstenedione by adult male subjects was 2.5 mug and of testosterone was 0.8 mug. For women, the mean excretion was 2.9 mug of androstenedione and 0.25 mug of testosterone. In pregnancy, androstenedione excretion was occasionally elevated above the normal range, but testosterone excretion was quite commonly increased. Some hirsute subjects exhibited an increase in androstenedione excretion, which was decreased by administration of dexamethasone. The results suggest that the amount of unconjugated testosterone in urine is not a direct reflection of the plasma free testosterone, but urinary androstenedione may be a useful reflection of plasma androstenedione levels.", "contents": "Excretion of non-conjugated androstenedione and testosterone in human urine. A method for the measurement of unconjugated testosterone and androstenedione in human urine is described. The method uses chromatographic separation followed by radioimmunoassay and has been examined for reliability. The mean 24-hour excretion of androstenedione by adult male subjects was 2.5 mug and of testosterone was 0.8 mug. For women, the mean excretion was 2.9 mug of androstenedione and 0.25 mug of testosterone. In pregnancy, androstenedione excretion was occasionally elevated above the normal range, but testosterone excretion was quite commonly increased. Some hirsute subjects exhibited an increase in androstenedione excretion, which was decreased by administration of dexamethasone. The results suggest that the amount of unconjugated testosterone in urine is not a direct reflection of the plasma free testosterone, but urinary androstenedione may be a useful reflection of plasma androstenedione levels."}
{"id": "PMID:189470", "title": "[Hyperplastic foci in chemical carcinogenesis].", "content": "Morphological, histochemical and biochemical perculiarities of liver hyperplastic nodules induced by different chemical carcinogens are regarded. The presence of basophylic atypical cells in the hyperplastic nodules, the possibility of transplantation of some nodules, the irreversibility of some morphological and biochemical lesions in these allows to designate hyperplastic nodules as a neoplasm. Enzyme and isozyme patterns in hyperplastic vesicles, the appearance of alpha-fetoprotein in these, and some other metabolic findings suggest biochemical disdifferentiation occurring in the vesicles. These findings suggest that cells of hyperplastic nodules are intermediate between normal and malignant cells in the course of neoplastic transformation.", "contents": "[Hyperplastic foci in chemical carcinogenesis]. Morphological, histochemical and biochemical perculiarities of liver hyperplastic nodules induced by different chemical carcinogens are regarded. The presence of basophylic atypical cells in the hyperplastic nodules, the possibility of transplantation of some nodules, the irreversibility of some morphological and biochemical lesions in these allows to designate hyperplastic nodules as a neoplasm. Enzyme and isozyme patterns in hyperplastic vesicles, the appearance of alpha-fetoprotein in these, and some other metabolic findings suggest biochemical disdifferentiation occurring in the vesicles. These findings suggest that cells of hyperplastic nodules are intermediate between normal and malignant cells in the course of neoplastic transformation."}
{"id": "PMID:189471", "title": "[Mechanism of biogenic monoamine stimulation of the enzymatic reduction of disulfides].", "content": "A possibility is shown to study the catecholamine (CA) action mechanism on the simple and available object, the liver supernatant fraction. Under these conditions the physiological concentrations of CA increase the disulphide reductase (DSR) activity. The effect of adrenaline, noradrenaline and isadrine (isopropylnoradrenaline) is realized through beta-receptors, the mesaton (phenylephrine) effect is realized through receptors differing from the classic ones. Serotonin stimulates DSR too but in an order higher concentration; this effect is blocked by beta-adrenolytic. For CA action the membrane factor is necessary, as the effect takes place only at protracted homogenization or preliminary solubilization by detergents. The additional data are obtained in favour of the hypothesis on the DSR activation through the chain: adenylate cyclase-3',5'-AMP-protein kinase.", "contents": "[Mechanism of biogenic monoamine stimulation of the enzymatic reduction of disulfides]. A possibility is shown to study the catecholamine (CA) action mechanism on the simple and available object, the liver supernatant fraction. Under these conditions the physiological concentrations of CA increase the disulphide reductase (DSR) activity. The effect of adrenaline, noradrenaline and isadrine (isopropylnoradrenaline) is realized through beta-receptors, the mesaton (phenylephrine) effect is realized through receptors differing from the classic ones. Serotonin stimulates DSR too but in an order higher concentration; this effect is blocked by beta-adrenolytic. For CA action the membrane factor is necessary, as the effect takes place only at protracted homogenization or preliminary solubilization by detergents. The additional data are obtained in favour of the hypothesis on the DSR activation through the chain: adenylate cyclase-3',5'-AMP-protein kinase."}
{"id": "PMID:189472", "title": "[Activity of NAD metabolism enzymes and DNA concentration in the liver during chicken ontogenesis].", "content": "A reverse interrelation is established between the content of NAD and DNA in the chickens liver at different stages of ontogenetic development, especially pronounced at the stages of embryogenesis. The content of NAD which is the least in the liver of the 8-day embryos increases with development of chickens and reaches the maximum level by the 6-month age. The content of DNA is maximum in the embryonal period. The activity of NAD-pyrophosphorylase in the liver nuclei has the low value at early periods of the embryonal life and rises with development of organism, reaching the constant values in one-, two- and 6-month chickens. Judging by the curve of the NAD-glycohydrolase activity in the liver nuclei, the hydrolase breakdown of NAD occurs only after chickens hatching.", "contents": "[Activity of NAD metabolism enzymes and DNA concentration in the liver during chicken ontogenesis]. A reverse interrelation is established between the content of NAD and DNA in the chickens liver at different stages of ontogenetic development, especially pronounced at the stages of embryogenesis. The content of NAD which is the least in the liver of the 8-day embryos increases with development of chickens and reaches the maximum level by the 6-month age. The content of DNA is maximum in the embryonal period. The activity of NAD-pyrophosphorylase in the liver nuclei has the low value at early periods of the embryonal life and rises with development of organism, reaching the constant values in one-, two- and 6-month chickens. Judging by the curve of the NAD-glycohydrolase activity in the liver nuclei, the hydrolase breakdown of NAD occurs only after chickens hatching."}
{"id": "PMID:189473", "title": "[Iso-octane soluble complex of cytochrome c with bovine brain phospholipids].", "content": "The conditions are determined for formation of the isooctane-soluble complex of cytochrome c with bull brain phospholipids. Molecular ratio protein/lipid in lipocytochrome c is 1 : 20 divided by 30. Ferri- and ferroforms of protein have different affinity to phospholipids. The ferrocytochrome c in the complex is subjected to self-oxidation in the absence of redox agents. Interaction of protein with phospholipids in water phase is shown to be of electrostatic nature. The cytochrome c conformation in water solution and in the complex does not differ significantly. But the mode of packing of lipid and protein molecules in the isooctane-soluble complex depends upon the degree of oxidation as has been shown by sedimentation methods. Cytochrome c maintains his conformation in a complex with phospholipids and retains the ability to redox reactions.", "contents": "[Iso-octane soluble complex of cytochrome c with bovine brain phospholipids]. The conditions are determined for formation of the isooctane-soluble complex of cytochrome c with bull brain phospholipids. Molecular ratio protein/lipid in lipocytochrome c is 1 : 20 divided by 30. Ferri- and ferroforms of protein have different affinity to phospholipids. The ferrocytochrome c in the complex is subjected to self-oxidation in the absence of redox agents. Interaction of protein with phospholipids in water phase is shown to be of electrostatic nature. The cytochrome c conformation in water solution and in the complex does not differ significantly. But the mode of packing of lipid and protein molecules in the isooctane-soluble complex depends upon the degree of oxidation as has been shown by sedimentation methods. Cytochrome c maintains his conformation in a complex with phospholipids and retains the ability to redox reactions."}
{"id": "PMID:189475", "title": "Phosphorylation of endogenous membrane proteins by endogenous protein kinase at the outer surface of Ehrlich cells.", "content": "An endogenous protein kinase at the surface of Ehrlich cells has been studied. Using exogenous (gamma32P)ATP as a phosphoryl group donator, a transfer was demonstrated into endogenous acceptor protein(s) as well as to exogenous phosvitin. Seryl- and threonyl-residues isolated from the endogenous and exogenous acceptor protein were found to be labeled. The ratio between the labeled phosphorylserine and phosphorylthreonine was about 3.5:1 for both the endogenous acceptor of the intact cells and the exogenous acceptor. In similar experiments with a membrane preparation from Ehrlich cells, this ratio increased to about 7:1 provided the exogenous acceptor protein was absent. The results were independent of whether 1 X 10(-5) M dibutyryl cyclic AMP was used or not with intact cells and a membrane fraction mainly consisting of vesicles. Whether the regulatory subunit of the membrane-associated protein kinase was in cis- or trans-disposition to the catalytic subunit no binding and dependence of the cyclic nucleotide was observed. Since the purified membrane fraction was considered free from endogenous cyclic AMP, it was concluded that the membrane-associated protein kinase of Ehrlich cells is not dependent on cyclic AMP. The critical role of arginine for the cyclic AMP dependence of the serine-containing residue in the catalytic subunit is discussed.", "contents": "Phosphorylation of endogenous membrane proteins by endogenous protein kinase at the outer surface of Ehrlich cells. An endogenous protein kinase at the surface of Ehrlich cells has been studied. Using exogenous (gamma32P)ATP as a phosphoryl group donator, a transfer was demonstrated into endogenous acceptor protein(s) as well as to exogenous phosvitin. Seryl- and threonyl-residues isolated from the endogenous and exogenous acceptor protein were found to be labeled. The ratio between the labeled phosphorylserine and phosphorylthreonine was about 3.5:1 for both the endogenous acceptor of the intact cells and the exogenous acceptor. In similar experiments with a membrane preparation from Ehrlich cells, this ratio increased to about 7:1 provided the exogenous acceptor protein was absent. The results were independent of whether 1 X 10(-5) M dibutyryl cyclic AMP was used or not with intact cells and a membrane fraction mainly consisting of vesicles. Whether the regulatory subunit of the membrane-associated protein kinase was in cis- or trans-disposition to the catalytic subunit no binding and dependence of the cyclic nucleotide was observed. Since the purified membrane fraction was considered free from endogenous cyclic AMP, it was concluded that the membrane-associated protein kinase of Ehrlich cells is not dependent on cyclic AMP. The critical role of arginine for the cyclic AMP dependence of the serine-containing residue in the catalytic subunit is discussed."}
{"id": "PMID:189476", "title": "Serum adenylate kinase activity in the early phase of acute myocardial infarction.", "content": "Elevated adenylate kinase activities in serum and urine have been studied among patients suffering from myocardial infarction. 71% of the patients had clearly increased activities in serum already on admission to the hospital, i.e. about 12 hours after onset of symptoms and patients was 45%. A maximum peak value of the activity in serum was seen at 6 hours after admission to the hospital, i.e. about 12 hrs after onset of symptoms and the elevated enzyme activity value persisted for at least 12 hours after admission. The patients with the elevated adenylate kinase activity in serum were arbitrarily divided into three groups as regards activity. It was shown that the difference in activity of ASAT as well as LD of the high and low activity group was significant (p less than 0.01). No such difference was established between these groups for ALAT, usually not being considered as a reliable test enzyme for myocardial infarction.", "contents": "Serum adenylate kinase activity in the early phase of acute myocardial infarction. Elevated adenylate kinase activities in serum and urine have been studied among patients suffering from myocardial infarction. 71% of the patients had clearly increased activities in serum already on admission to the hospital, i.e. about 12 hours after onset of symptoms and patients was 45%. A maximum peak value of the activity in serum was seen at 6 hours after admission to the hospital, i.e. about 12 hrs after onset of symptoms and the elevated enzyme activity value persisted for at least 12 hours after admission. The patients with the elevated adenylate kinase activity in serum were arbitrarily divided into three groups as regards activity. It was shown that the difference in activity of ASAT as well as LD of the high and low activity group was significant (p less than 0.01). No such difference was established between these groups for ALAT, usually not being considered as a reliable test enzyme for myocardial infarction."}
{"id": "PMID:189479", "title": "Naturally-occurring neonatal canine herpesvirus infection.", "content": "The detailed clinical and epidemiological history and the pathology of neonatal canine herpesvirus (CHV) disease in a naturally infected litter of pups is reported. Herpesvirus was isolated from the brain, lung, liver, spleen, kidney and intestine of one of the affected litter which died on day 10 after whelping. The isolation of virus correlated with the distinctive gross and histological changes in these organs. Herpesvirus was isolated also from the anterior vagina of the bitch 18 days after whelping --a finding which may be of significance in the epidemiology of the natural disease.", "contents": "Naturally-occurring neonatal canine herpesvirus infection. The detailed clinical and epidemiological history and the pathology of neonatal canine herpesvirus (CHV) disease in a naturally infected litter of pups is reported. Herpesvirus was isolated from the brain, lung, liver, spleen, kidney and intestine of one of the affected litter which died on day 10 after whelping. The isolation of virus correlated with the distinctive gross and histological changes in these organs. Herpesvirus was isolated also from the anterior vagina of the bitch 18 days after whelping --a finding which may be of significance in the epidemiology of the natural disease."}
{"id": "PMID:189483", "title": "[Testing the preventive properties of polyvalent inactivated vaccine (IBR, PI-3, Adenovirus 1,3) at a cattle-breeding farm].", "content": "Tested was an inactivated polyvalent vaccine. It was shown to produce virus-neutralizing antibodies against the respiratory viruses in high titers. The vaccine proved highly immunogenic, reactogenic, and harmless in doses of 2,3,5,7, and 10 cm3 for 30-45-day-old calves and pregnant cows in their 7th or 8th month of pregnancy. The morbidity rate among the unvaccinated calves ranged from 51 to 66 per cent, and among the vaccinated ones it was from 0 to 5 per cent on the four farms studied. The abortions caused by the IBR vicontrol was cows about 17 per cent, and with the vaccinated ones it was 1.14 per cent. Calves born by untreated control cows contracted respiratory virus infections (76 per cent), while calves from vaccinated cows did not. When there was an acute virus respiratory disease on the farms all calves were treated with a hyper-immune serum against respiratory viruses, and after recovery of the herd vaccinations and revaccinations of all calves were carried out. Discussed is the problem of the protection  properties of the vaccine in the case of pregnant cows and its advantages as compared with the live vaccines in order to discontinue the transmission of live viruses onto the industrial cattle-breeding farms.", "contents": "[Testing the preventive properties of polyvalent inactivated vaccine (IBR, PI-3, Adenovirus 1,3) at a cattle-breeding farm]. Tested was an inactivated polyvalent vaccine. It was shown to produce virus-neutralizing antibodies against the respiratory viruses in high titers. The vaccine proved highly immunogenic, reactogenic, and harmless in doses of 2,3,5,7, and 10 cm3 for 30-45-day-old calves and pregnant cows in their 7th or 8th month of pregnancy. The morbidity rate among the unvaccinated calves ranged from 51 to 66 per cent, and among the vaccinated ones it was from 0 to 5 per cent on the four farms studied. The abortions caused by the IBR vicontrol was cows about 17 per cent, and with the vaccinated ones it was 1.14 per cent. Calves born by untreated control cows contracted respiratory virus infections (76 per cent), while calves from vaccinated cows did not. When there was an acute virus respiratory disease on the farms all calves were treated with a hyper-immune serum against respiratory viruses, and after recovery of the herd vaccinations and revaccinations of all calves were carried out. Discussed is the problem of the protection  properties of the vaccine in the case of pregnant cows and its advantages as compared with the live vaccines in order to discontinue the transmission of live viruses onto the industrial cattle-breeding farms."}
{"id": "PMID:189484", "title": "[Use of indirect complement fixation test for studying foot and mouth disease virus].", "content": "The indirect complement-fixation test was used in experiments for the subtype differentiation, and with the agar gel diffusion and the serum neutralization test was studied the immunity in cattle that had already recovered from foot-and-mouth disease or were immunized against the disease. It was found that the indirect complement-fixation test is instrumental in the demonstration of the antigenic differences between the foot-and-mouth viruses. Comparative experiments have shown that the indirect test in this case is more expedient and of higher economic value than the direct CF reactions after Traub and M\u00f6hlmann and after Marucci. The assessment of the results of comparative investigations of sera carried out by the indirect complement-fixation test, the agar gel diffusion test, and the serum neutralization reaction revealed that the indirect reaction is a convenient, quick, and prompt method of work. Discussed is the sensitivity of the reaction and its advantages and its advantages in studies on a large scale on the immune status of animals immunized against F.M.D. or animals that have recovered from the disease.", "contents": "[Use of indirect complement fixation test for studying foot and mouth disease virus]. The indirect complement-fixation test was used in experiments for the subtype differentiation, and with the agar gel diffusion and the serum neutralization test was studied the immunity in cattle that had already recovered from foot-and-mouth disease or were immunized against the disease. It was found that the indirect complement-fixation test is instrumental in the demonstration of the antigenic differences between the foot-and-mouth viruses. Comparative experiments have shown that the indirect test in this case is more expedient and of higher economic value than the direct CF reactions after Traub and M\u00f6hlmann and after Marucci. The assessment of the results of comparative investigations of sera carried out by the indirect complement-fixation test, the agar gel diffusion test, and the serum neutralization reaction revealed that the indirect reaction is a convenient, quick, and prompt method of work. Discussed is the sensitivity of the reaction and its advantages and its advantages in studies on a large scale on the immune status of animals immunized against F.M.D. or animals that have recovered from the disease."}
{"id": "PMID:189485", "title": "[Effect of iosan and bradofen on the viruses of Newcastle disease, laryngotracheitis and fowl pox].", "content": "Tested was the effect of the iodoform preparation iosan and the quaternary ammonium preparation bradofen against the viruses of the Newcastle disease (strain La Sota), laryngotracheitis (strain TsNIIP) and fowl pox (strain FK) in birds. The following results were obtained: 1. To a concentration of 3% (262 ppm of active iodine) and exposure of 45 min. to iosan the virus of laryngotracheitis was sensitive; that of Newcastle disease perished at a conc. of 5% (525 ppm of active iodine for 15 min); and that of fowl pox was not inactivated at a 30 min. exposure to a conc. of 7% (875 ppm of active iodine.) 2. Bradofen inactivated the Newcastle disease virus in a conc. of 0.5 per cent for 30 min., while the pox virus withstood a conc. of 1.5% up to the 30 th min. The virus of laryngotracheitis was inactivated by a conc. of 2 per cent for 45 min. The disinfection effect of the tested preparations was assessed as satisfactory.", "contents": "[Effect of iosan and bradofen on the viruses of Newcastle disease, laryngotracheitis and fowl pox]. Tested was the effect of the iodoform preparation iosan and the quaternary ammonium preparation bradofen against the viruses of the Newcastle disease (strain La Sota), laryngotracheitis (strain TsNIIP) and fowl pox (strain FK) in birds. The following results were obtained: 1. To a concentration of 3% (262 ppm of active iodine) and exposure of 45 min. to iosan the virus of laryngotracheitis was sensitive; that of Newcastle disease perished at a conc. of 5% (525 ppm of active iodine for 15 min); and that of fowl pox was not inactivated at a 30 min. exposure to a conc. of 7% (875 ppm of active iodine.) 2. Bradofen inactivated the Newcastle disease virus in a conc. of 0.5 per cent for 30 min., while the pox virus withstood a conc. of 1.5% up to the 30 th min. The virus of laryngotracheitis was inactivated by a conc. of 2 per cent for 45 min. The disinfection effect of the tested preparations was assessed as satisfactory."}
{"id": "PMID:189486", "title": "[Several features of Aujeszky disease virus].", "content": "Clinical, virological, and morphological investigations were carried out on a total of 36 rabbits experimentally infected with five strains of the Aujeszky's disease virus. Those of the test animals that were infected with strain K did not die or died showing no clinical manifestations; those infected with strains K1. B, and TB showed nervous disturbances and died strongly scratching the site of injection. The animals infected with strain KB exhibited respiratory disturbances showing no death cases. Histopathologically, nonpurulent meningoencephalitis of the central nervous system was established in all animals. The rabbits infected with strain K (resistant to trypsin and temperature changes) and those infected with strain KB these lesions were more slightly expressed. The lungs of the affected animals showed interstitial intralobular phenomonia of a lympho-histiocytic type as a reactive necroses in the liver and spleen. In the case of K1, B, and TB infections no changes in the lungs and spleen were noticed, however, the liver was analogously affected. Results showed that those of those of the strains that were with lower virulence did not cause the clinical picture of scratching; such strains proved neurotropic and even strongly pheumotropic. It is concluded that the clinical and morphologic aspects observed in experimentally infected rabbits can be referred to in diagnosing the causative agent, differentiating strains that are slightly pathogenic from strains that are pathogenic.", "contents": "[Several features of Aujeszky disease virus]. Clinical, virological, and morphological investigations were carried out on a total of 36 rabbits experimentally infected with five strains of the Aujeszky's disease virus. Those of the test animals that were infected with strain K did not die or died showing no clinical manifestations; those infected with strains K1. B, and TB showed nervous disturbances and died strongly scratching the site of injection. The animals infected with strain KB exhibited respiratory disturbances showing no death cases. Histopathologically, nonpurulent meningoencephalitis of the central nervous system was established in all animals. The rabbits infected with strain K (resistant to trypsin and temperature changes) and those infected with strain KB these lesions were more slightly expressed. The lungs of the affected animals showed interstitial intralobular phenomonia of a lympho-histiocytic type as a reactive necroses in the liver and spleen. In the case of K1, B, and TB infections no changes in the lungs and spleen were noticed, however, the liver was analogously affected. Results showed that those of those of the strains that were with lower virulence did not cause the clinical picture of scratching; such strains proved neurotropic and even strongly pheumotropic. It is concluded that the clinical and morphologic aspects observed in experimentally infected rabbits can be referred to in diagnosing the causative agent, differentiating strains that are slightly pathogenic from strains that are pathogenic."}
{"id": "PMID:189487", "title": "[Attempts to adapt BNK cells to cultivation in suspension and study of the antigenic properties of foot-and-mouth diseases viruses obtained from them].", "content": "Experiments were carried out to cultivate the foot-and-mouth disease virus under laboratory conditions in a suspension of the BHK-21 cell line. Results showed that the number of cells cultivated in a susfor 48 to 72 hours of incubation reaches up to 2.2 X 10(6). It was also found that certain conditions should be observed for the successful cultivation of the cells in suspension, such as aeration, pH, and respective temperature. It was demonstrated that foot-and-mouth diseases viruses obtained from BHK cells propagating in suspension possess good antigenic and immunogenic properties.", "contents": "[Attempts to adapt BNK cells to cultivation in suspension and study of the antigenic properties of foot-and-mouth diseases viruses obtained from them]. Experiments were carried out to cultivate the foot-and-mouth disease virus under laboratory conditions in a suspension of the BHK-21 cell line. Results showed that the number of cells cultivated in a susfor 48 to 72 hours of incubation reaches up to 2.2 X 10(6). It was also found that certain conditions should be observed for the successful cultivation of the cells in suspension, such as aeration, pH, and respective temperature. It was demonstrated that foot-and-mouth diseases viruses obtained from BHK cells propagating in suspension possess good antigenic and immunogenic properties."}
{"id": "PMID:189488", "title": "Ultrastructure of the neuroglial fatty metamorphosis (Virchow) in the perinatal period.", "content": "The ultrastructure of neuroglial fatty metamorphosis (GFM) has been investigated in the telencephalic white matter of 12 premature and mature infants (gestational age 22-40 weeks; survival 0-96 days). GFM was found in all cases apart from a 22-week-old fetus, and involves predominantly astrocytic cells (68.8%), then glioblasts (43.5%), but only 7.4% of oligodendrocytes. GFM, therefore, seems to be independent of the myelination process and indicates the vulnerability of the immature neuroglial population in the metabolic and circulatory disorders of the perinatal period. Since GFM is found in almost all children dying within the early postnatal period, this subtle alteration reflects a special form of minimal brain damage. The relationship between GFM, astrocytic hypertrophy and periventricular leucomalacia and their role in the telencephalic leucoencephalopathy are discussed.", "contents": "Ultrastructure of the neuroglial fatty metamorphosis (Virchow) in the perinatal period. The ultrastructure of neuroglial fatty metamorphosis (GFM) has been investigated in the telencephalic white matter of 12 premature and mature infants (gestational age 22-40 weeks; survival 0-96 days). GFM was found in all cases apart from a 22-week-old fetus, and involves predominantly astrocytic cells (68.8%), then glioblasts (43.5%), but only 7.4% of oligodendrocytes. GFM, therefore, seems to be independent of the myelination process and indicates the vulnerability of the immature neuroglial population in the metabolic and circulatory disorders of the perinatal period. Since GFM is found in almost all children dying within the early postnatal period, this subtle alteration reflects a special form of minimal brain damage. The relationship between GFM, astrocytic hypertrophy and periventricular leucomalacia and their role in the telencephalic leucoencephalopathy are discussed."}
{"id": "PMID:189489", "title": "Hemangiosarcoma and hepatocellular carcinoma of the liver following vinyl chloride exposure. A report of two cases.", "content": "A report is given of the clinical and autopsy findings of two men who died from malignant liver neoplasm following occupational exposure to vinyl chloride. The first patient was a 44-year-old man with an hemangiosarcoma of the liver, the second patient a 67-year-old man with an hepatocellular carcinoma. So far an hepatocellular carcinoma due to vinyl chloride has not yet been observed in man. Its occurrence, however, has been suggested from the results of animal experiments. The connection of hepatocellular carcinoma with exposure to vinyl chloride is discussed.", "contents": "Hemangiosarcoma and hepatocellular carcinoma of the liver following vinyl chloride exposure. A report of two cases. A report is given of the clinical and autopsy findings of two men who died from malignant liver neoplasm following occupational exposure to vinyl chloride. The first patient was a 44-year-old man with an hemangiosarcoma of the liver, the second patient a 67-year-old man with an hepatocellular carcinoma. So far an hepatocellular carcinoma due to vinyl chloride has not yet been observed in man. Its occurrence, however, has been suggested from the results of animal experiments. The connection of hepatocellular carcinoma with exposure to vinyl chloride is discussed."}
{"id": "PMID:189504", "title": "[Physico-chemical and immunological parameters of C-type oncornavirus produced by transplantable Syrian hamster cell line].", "content": "The results of investigations of oncornavirus produced by the continuous Syrian hamster cell line (cell culture 100) are presented. The virus isolated is a hamster C-type oncornavirus according to its physico-chemical and immunological properties.", "contents": "[Physico-chemical and immunological parameters of C-type oncornavirus produced by transplantable Syrian hamster cell line]. The results of investigations of oncornavirus produced by the continuous Syrian hamster cell line (cell culture 100) are presented. The virus isolated is a hamster C-type oncornavirus according to its physico-chemical and immunological properties."}
{"id": "PMID:189505", "title": "[Study of gallium-67 citrate distribution in rat tumors].", "content": "In rats with transplantable tumors of different histological structure the authors have studied the dynamics of gallium-67 citrate distribution in tumors, adjacent tissues and blood. It has been found that gallium-67 is able to be accumulated in increased amounts in all tumors irrespective of their histological type. Tumor image in scannograms was mostly distinct on the 2--3d day after injection of gallium-67 citrate, when there was the greatest difference in accumulation of the isotope in the tumor and surrounding \"intact\" tissues.", "contents": "[Study of gallium-67 citrate distribution in rat tumors]. In rats with transplantable tumors of different histological structure the authors have studied the dynamics of gallium-67 citrate distribution in tumors, adjacent tissues and blood. It has been found that gallium-67 is able to be accumulated in increased amounts in all tumors irrespective of their histological type. Tumor image in scannograms was mostly distinct on the 2--3d day after injection of gallium-67 citrate, when there was the greatest difference in accumulation of the isotope in the tumor and surrounding \"intact\" tissues."}
{"id": "PMID:189506", "title": "[Autoradiographic study of the gastric mucosa in cancer].", "content": "A summary of main successes in the field of diagnosis and therapy of lymphogranulomatosis is given. The most informative methods of diagnosis that need further development are estimated. Therapeutic schemes that are to be further pinpointed (radiation, pharmacological and combined) as well as possible prospective trends in studying the pathogenesis (the technic of cultivation, an estimate of the immunological status) are being formulated, due to that the therapeutic policy might be substantially modified.", "contents": "[Autoradiographic study of the gastric mucosa in cancer]. A summary of main successes in the field of diagnosis and therapy of lymphogranulomatosis is given. The most informative methods of diagnosis that need further development are estimated. Therapeutic schemes that are to be further pinpointed (radiation, pharmacological and combined) as well as possible prospective trends in studying the pathogenesis (the technic of cultivation, an estimate of the immunological status) are being formulated, due to that the therapeutic policy might be substantially modified."}
{"id": "PMID:189502", "title": "[Effect of cyclic-3',5'-AMP on rat liver polynucleotide phosphorylase activity].", "content": "Effect of cAMP on the activity of polynucleotide phosphorylase (PNPase) was studied in polyribosome fraction of rat liver tissue. Intraperitonel administration of cAMP or of theophilline into rats distinctly decreased the PNPase activity in the polyribosome fraction. The cAMP (1-10(-4) M) inhibited the enzymatic activity only by 8% in polyribosome fraction in vitro, as it was estimated by the reaction of phosphorolysis of endogenous RNA and polyA added. Any attempts were proved to be uncucessful to reveal cAMP, ATP-dependent proteinkinase in rat liver, responsible for the decrease in the PNPase activity in the polyribosome fraction. The cAMP inhibited the increase in the PNPase activity, coupled with protein biosynthesis in polyribosomes. Moreover, cAMP caused a decrease in the PNPase activity in reaction of polyA phosphorolysis and did not affect the rate of endogenous RNA phosphorolysis in polyribosome fraction, isolated from postmitochondrial fraction after incubation for 15 min at 30 degrees. The 3',5'-cyclo AMP (2-10(-6)-2-10(-4) M) stimulated incorporation of 14C-leucine into acid-insoluble material, when postmitochondrial fraction was incubated under the same conditions. The data obtained suggest that cAMP either inhibits specifically the PNPase synthesis or represses the coupled with protein biosynthesis formation of active \"heavy\" type of PNPase from less active \"light\" type.", "contents": "[Effect of cyclic-3',5'-AMP on rat liver polynucleotide phosphorylase activity]. Effect of cAMP on the activity of polynucleotide phosphorylase (PNPase) was studied in polyribosome fraction of rat liver tissue. Intraperitonel administration of cAMP or of theophilline into rats distinctly decreased the PNPase activity in the polyribosome fraction. The cAMP (1-10(-4) M) inhibited the enzymatic activity only by 8% in polyribosome fraction in vitro, as it was estimated by the reaction of phosphorolysis of endogenous RNA and polyA added. Any attempts were proved to be uncucessful to reveal cAMP, ATP-dependent proteinkinase in rat liver, responsible for the decrease in the PNPase activity in the polyribosome fraction. The cAMP inhibited the increase in the PNPase activity, coupled with protein biosynthesis in polyribosomes. Moreover, cAMP caused a decrease in the PNPase activity in reaction of polyA phosphorolysis and did not affect the rate of endogenous RNA phosphorolysis in polyribosome fraction, isolated from postmitochondrial fraction after incubation for 15 min at 30 degrees. The 3',5'-cyclo AMP (2-10(-6)-2-10(-4) M) stimulated incorporation of 14C-leucine into acid-insoluble material, when postmitochondrial fraction was incubated under the same conditions. The data obtained suggest that cAMP either inhibits specifically the PNPase synthesis or represses the coupled with protein biosynthesis formation of active \"heavy\" type of PNPase from less active \"light\" type."}
{"id": "PMID:189503", "title": "[Sequence of conversion of pregnenolone into androgens in virilizing adrenal glands in man].", "content": "Trace amounts of labelled pregnenolone were added to the slices of veriliscent tumor from human adrenal gland in order to study the stepwise conversion of the steroid into androstenedione, 11betaOH-androstenedione and their intermediats--17-alpha-OH pregnenolone, dehydroepiandrosterone, progesterone, and 17-alpha-OH-progesterone. The definite sequence was observed in the maximal incorporation of pregnenolone label into 17-alpha-OH-pregnenolone (2-5 min of incubation) leads to dehydroepiandrosterone (5-15 min) leads to androstenedione (10-20 min). Incorporation of the pregnenolone label into 17-alpha-OH-pregnenolone and dehydroepiandrosterone was distinctly higher than into progesterone and 17-alpha-OH-progesterone in all the experiments within all the studied periods of incubation. The data obtained suggest that in viriliscent tumors of adrenal gland conversion of pregnenolone into androgens proceeded as follows: pregnenolone leads to 17-alpha-OH-pregnenolone leads to dehydroepiandrosterone leads to androstenedione. When formation of androstenedione and 11beta-OH-androstenedione from pregnenolone and progesterone was analyzed during the experiment it was shown that 11-beta-OH-androstenedione was mainly formed via androstenedione and the hormone was the end product of the androgen synthesis.", "contents": "[Sequence of conversion of pregnenolone into androgens in virilizing adrenal glands in man]. Trace amounts of labelled pregnenolone were added to the slices of veriliscent tumor from human adrenal gland in order to study the stepwise conversion of the steroid into androstenedione, 11betaOH-androstenedione and their intermediats--17-alpha-OH pregnenolone, dehydroepiandrosterone, progesterone, and 17-alpha-OH-progesterone. The definite sequence was observed in the maximal incorporation of pregnenolone label into 17-alpha-OH-pregnenolone (2-5 min of incubation) leads to dehydroepiandrosterone (5-15 min) leads to androstenedione (10-20 min). Incorporation of the pregnenolone label into 17-alpha-OH-pregnenolone and dehydroepiandrosterone was distinctly higher than into progesterone and 17-alpha-OH-progesterone in all the experiments within all the studied periods of incubation. The data obtained suggest that in viriliscent tumors of adrenal gland conversion of pregnenolone into androgens proceeded as follows: pregnenolone leads to 17-alpha-OH-pregnenolone leads to dehydroepiandrosterone leads to androstenedione. When formation of androstenedione and 11beta-OH-androstenedione from pregnenolone and progesterone was analyzed during the experiment it was shown that 11-beta-OH-androstenedione was mainly formed via androstenedione and the hormone was the end product of the androgen synthesis."}
{"id": "PMID:189508", "title": "[Morphology and classification of secondary tumors of the ovaries].", "content": "Based on histomorphological study of over 200 observations, the author suggests the morphological characteristics of basic varieties of secondary ovarian tumors. Some aspects of the nomenclature are discussed, and the classification of neoplasms under consideration is presented. Among epithelial secondary tumors of the ovaries special attention is given to Krukenberg tumor and metastases of cancer with \"functioning stroma\". The classification also takes into account mesenchymal, neurogenic, hemopoietic and other tumors.", "contents": "[Morphology and classification of secondary tumors of the ovaries]. Based on histomorphological study of over 200 observations, the author suggests the morphological characteristics of basic varieties of secondary ovarian tumors. Some aspects of the nomenclature are discussed, and the classification of neoplasms under consideration is presented. Among epithelial secondary tumors of the ovaries special attention is given to Krukenberg tumor and metastases of cancer with \"functioning stroma\". The classification also takes into account mesenchymal, neurogenic, hemopoietic and other tumors."}
{"id": "PMID:189514", "title": "[IgM diagnosis of Epstein-Barr virus (EBV) infections by means of the immunofluorescent method].", "content": "Sera were investigated of patients possibly suffering from an EBV infection, without showing clinical features characteristic of infectious mononucleosis. The method of investigation was the detection of antibodies of the IgM-type by means of the immunofluorescent method using a three-layer technique. Diagnosis of EBV infection was established in 10 out of 90 patients with facial palsy, one with myelitis, one with sudden deafness and one with polyneuritis. In addition, 4 out of 19 cases of hepatitis (Hbs-negative) proved to be due to infection with EBV. The specific IgM test proved to be superior to the heterophil agglutination test.", "contents": "[IgM diagnosis of Epstein-Barr virus (EBV) infections by means of the immunofluorescent method]. Sera were investigated of patients possibly suffering from an EBV infection, without showing clinical features characteristic of infectious mononucleosis. The method of investigation was the detection of antibodies of the IgM-type by means of the immunofluorescent method using a three-layer technique. Diagnosis of EBV infection was established in 10 out of 90 patients with facial palsy, one with myelitis, one with sudden deafness and one with polyneuritis. In addition, 4 out of 19 cases of hepatitis (Hbs-negative) proved to be due to infection with EBV. The specific IgM test proved to be superior to the heterophil agglutination test."}
{"id": "PMID:189515", "title": "[The action of silymarin on Galactosamine-induced hepatitis in the rat (author's transl)].", "content": "The hepatoprotective action of Silymarin was studied in 65 male Wistar rats, prior to and following D-galactosamine intoxication. There was a marked reduction in the histological and ultrastructural changes in the nucleolus, nuclear membrane, mitochondria, granular and agranular endoplasmic reticulum and lysosomes of the liver cell and also in the Kupffer stellate cells. The reduction in glycogen and RNA loss was determined biochemically. The activities of many enzymes were kept constant (oxidoreductases, NADH2 diaphorase, G-6-phosphatase, Mg++ and K+/Na+-dependent ATPases, acid phosphatases).", "contents": "[The action of silymarin on Galactosamine-induced hepatitis in the rat (author's transl)]. The hepatoprotective action of Silymarin was studied in 65 male Wistar rats, prior to and following D-galactosamine intoxication. There was a marked reduction in the histological and ultrastructural changes in the nucleolus, nuclear membrane, mitochondria, granular and agranular endoplasmic reticulum and lysosomes of the liver cell and also in the Kupffer stellate cells. The reduction in glycogen and RNA loss was determined biochemically. The activities of many enzymes were kept constant (oxidoreductases, NADH2 diaphorase, G-6-phosphatase, Mg++ and K+/Na+-dependent ATPases, acid phosphatases)."}
{"id": "PMID:189517", "title": "[Age dependence of adenylate cyclase activity and cAMP generation in aortas and femoral arteries of rats (author's transl)].", "content": "It is well-known that the cAMP-adenylate cyclase system is important in mediating the effects of numerous hormones. We investigated the age-dependent behaviour of this system in aortas and femoral arteries of male Wistar rats (at the age of 10 days, 1, 4, 8, 12, and 22 months). 1. The basic adenylate cyclase activity had considerably been decreased beyond the first month of life, thereafter it was almost constant. 2. The response of adenylate cyclase to guanylyl-imidodiphosphate and NaF had essentially been elevated since the 4th month of age. 3. The possibility of stimulating the cAMP generation due to epinephrine and histamine had substantially been increased since the 12th month of age.", "contents": "[Age dependence of adenylate cyclase activity and cAMP generation in aortas and femoral arteries of rats (author's transl)]. It is well-known that the cAMP-adenylate cyclase system is important in mediating the effects of numerous hormones. We investigated the age-dependent behaviour of this system in aortas and femoral arteries of male Wistar rats (at the age of 10 days, 1, 4, 8, 12, and 22 months). 1. The basic adenylate cyclase activity had considerably been decreased beyond the first month of life, thereafter it was almost constant. 2. The response of adenylate cyclase to guanylyl-imidodiphosphate and NaF had essentially been elevated since the 4th month of age. 3. The possibility of stimulating the cAMP generation due to epinephrine and histamine had substantially been increased since the 12th month of age."}
{"id": "PMID:189520", "title": "Polychlorinated biphenyl(s) as a promotor in experimental hepatocarcinogenesis in rats.", "content": "The effects of dietary polychlorinated biphenyls (PCBs) on hepatocarcinogenesis in female rats of Donryu strain receiving 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) were investigated. Oral administration of PCBs after administration of 3'-Me-DAB resulted in a high incidence (64%) of hepatocarcinoma. In contrast, administration of a similar amount of PCBs before, or together with 3'-Me-DAB did not induce hepatic tumors. Administration of a slightly larger amount of PCBs alone did not induce liver tumors, while administration of a slightly larger amount of 3'-Me-DAB alone caused only a low incidence (13%) of hepatocarcinoma. These results strongly suggest that PCBs exert a potent promoting action in experimental azo dye hepatocarcinogenesis.", "contents": "Polychlorinated biphenyl(s) as a promotor in experimental hepatocarcinogenesis in rats. The effects of dietary polychlorinated biphenyls (PCBs) on hepatocarcinogenesis in female rats of Donryu strain receiving 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) were investigated. Oral administration of PCBs after administration of 3'-Me-DAB resulted in a high incidence (64%) of hepatocarcinoma. In contrast, administration of a similar amount of PCBs before, or together with 3'-Me-DAB did not induce hepatic tumors. Administration of a slightly larger amount of PCBs alone did not induce liver tumors, while administration of a slightly larger amount of 3'-Me-DAB alone caused only a low incidence (13%) of hepatocarcinoma. These results strongly suggest that PCBs exert a potent promoting action in experimental azo dye hepatocarcinogenesis."}
{"id": "PMID:189525", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat I. the determination of the triphosphatase and diphosphatase activities in tissue (author's transl)].", "content": "The determination of the tripolyphosphatase and diphosphatase activities in minced muscular tissue is described. This determination bases on the rate of breakdown of added tripolyphosphate and diphosphate respectively. The kinetic of the polyphosphatase effect with regard to the evaluation of the data is discussed whereby a mathematical description of the substrate activated breakdown of disphosphate by means of the polynomic regression is included.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat I. the determination of the triphosphatase and diphosphatase activities in tissue (author's transl)]. The determination of the tripolyphosphatase and diphosphatase activities in minced muscular tissue is described. This determination bases on the rate of breakdown of added tripolyphosphate and diphosphate respectively. The kinetic of the polyphosphatase effect with regard to the evaluation of the data is discussed whereby a mathematical description of the substrate activated breakdown of disphosphate by means of the polynomic regression is included."}
{"id": "PMID:189521", "title": "Expression of virus specific morphological cell transformation induced in enucleated cells.", "content": "Chick embryo fibroblasts infected by a temperature sensitive mutant of Rous sarcoma virus were enucleated with Cytochalasin B. The cytoplasts were still able to transform morphologically when shifted from nonpermissive to permissive temperature, and to revert ot normal morphology when shifted from permissive to nonpermissive temperature. This indicates that the viral gene product responsible for transformation acts primarily on cytoplasmic or membrane components and not on the nucleus.", "contents": "Expression of virus specific morphological cell transformation induced in enucleated cells. Chick embryo fibroblasts infected by a temperature sensitive mutant of Rous sarcoma virus were enucleated with Cytochalasin B. The cytoplasts were still able to transform morphologically when shifted from nonpermissive to permissive temperature, and to revert ot normal morphology when shifted from permissive to nonpermissive temperature. This indicates that the viral gene product responsible for transformation acts primarily on cytoplasmic or membrane components and not on the nucleus."}
{"id": "PMID:189526", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat II. occurence of tripolyphosphatase in muscular tissue (author's transl)].", "content": "After a review on the present knowledge of the occurence of tripolyphosphatase in muscular tissue own data of the tripolyphosphatase activity in the bovine longissimus muscle of seven animals are reported. Remarkable differences between animals were observed which seem to depend on the pH of tissue.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat II. occurence of tripolyphosphatase in muscular tissue (author's transl)]. After a review on the present knowledge of the occurence of tripolyphosphatase in muscular tissue own data of the tripolyphosphatase activity in the bovine longissimus muscle of seven animals are reported. Remarkable differences between animals were observed which seem to depend on the pH of tissue."}
{"id": "PMID:189527", "title": "[A so-called adamantinoma of the right femur (author's transl)].", "content": "Report on a so-called adamantinoma of a right femur (fourth case from available publications) with remarks on the histogenesis of these tumors, which show correlating properties with malignant synovialomas. In other words, the so-called adamantinoma of long bones represents the osseous form of a malignant synovialoma, whereby an intraosseous ganglion has to be considered as a histogenetic criterion (matrix).", "contents": "[A so-called adamantinoma of the right femur (author's transl)]. Report on a so-called adamantinoma of a right femur (fourth case from available publications) with remarks on the histogenesis of these tumors, which show correlating properties with malignant synovialomas. In other words, the so-called adamantinoma of long bones represents the osseous form of a malignant synovialoma, whereby an intraosseous ganglion has to be considered as a histogenetic criterion (matrix)."}
{"id": "PMID:189524", "title": "[Effect of etimizol on super-slow electrical oscillations and the concentration of noradrenaline in nuclei of the rabbit hypothalamus].", "content": "Following intramuscular administration of a 2.5 mg/kg dose of ethymisol to curarized rabbits with implanted gold electrodes in the anterior group of hypothalamic nuclei, a correlation was revelaed between the amplitude of superslow electrical oscillations of 0 to 1 c/s and the noradrenaline content in the brain tissue. After ethymisol administration, the positive wave of the slow oscillation disappeared, while the adrenaline content in the hypothalamic area decreased from 0.93 mkg/g to 0.16 mkg/g of the tissue. By means of phentolamine and propranolol adrenoblockators the participation of alpha-and beta-receptors of the hypothalamus in the ethymisol effect has been proved.", "contents": "[Effect of etimizol on super-slow electrical oscillations and the concentration of noradrenaline in nuclei of the rabbit hypothalamus]. Following intramuscular administration of a 2.5 mg/kg dose of ethymisol to curarized rabbits with implanted gold electrodes in the anterior group of hypothalamic nuclei, a correlation was revelaed between the amplitude of superslow electrical oscillations of 0 to 1 c/s and the noradrenaline content in the brain tissue. After ethymisol administration, the positive wave of the slow oscillation disappeared, while the adrenaline content in the hypothalamic area decreased from 0.93 mkg/g to 0.16 mkg/g of the tissue. By means of phentolamine and propranolol adrenoblockators the participation of alpha-and beta-receptors of the hypothalamus in the ethymisol effect has been proved."}
{"id": "PMID:189528", "title": "[Metastasizing islet cell carcinoma of the pancreas in a 10-year-old girl (author's transl)].", "content": "A medullary islet cell carcinoma of the pancreas with liver and peritoneal metastases was found at autopsy of a 10-year-old girl. Ultrastructurally, the carcinoma cells showed typical secretion granules resembling prevailingly A1 (D) cell granules in pancreatic islets. Silver impregnation according to Hellerstr\u00f6m and Hellman (1960) for demonstration of A1 islet cells was moderately positive in the tumor cells. Therefore, it is suggested that the presented metastasizing islet cell carcinoma may have derived from A1 islet cells.", "contents": "[Metastasizing islet cell carcinoma of the pancreas in a 10-year-old girl (author's transl)]. A medullary islet cell carcinoma of the pancreas with liver and peritoneal metastases was found at autopsy of a 10-year-old girl. Ultrastructurally, the carcinoma cells showed typical secretion granules resembling prevailingly A1 (D) cell granules in pancreatic islets. Silver impregnation according to Hellerstr\u00f6m and Hellman (1960) for demonstration of A1 islet cells was moderately positive in the tumor cells. Therefore, it is suggested that the presented metastasizing islet cell carcinoma may have derived from A1 islet cells."}
{"id": "PMID:189529", "title": "Studies on the phyllosphere microflora of tapioca (Manihot utilissima Pohl).", "content": "Studies on the phyllosphere microflora of tapioca (Manihot utilissima Pohl.) revealed that incidence of bacteria, fungi, and actinomycetes is indipendent of the variety, but dependent on the age. The bacteria and fungi increased with increasing age of the leaf and were more on mature leaves, whereas no such difference was noticed in the occurrence of actinomycetes. The large majority of the isolates, that were Gram-negative bacteria, was also amino acid-requiring. The chromogenic types occurred in greater abundance. The phyllosphere mycoflora consisted mainly of species of Asperigullus, Penicillium, Mucor, Curvularia, Alternaria, Helminthosporium, Fusarium, Hormicium, and Pullularia, at first three being predominant. There was no correlation between HCN content of leaves and microorganisms in the phyllosphere, Regarding the interrelationship between different groups of microorganisms in the phyllosphere, a positive correlation between fungi and actinomycetes and bacteria and actinomycetes in two (M. 4 and H. 105/44) varieties and a negative correlation for fungi and actinomycetes in one (H. 12/49) were obtained. The effect of leaf exudate and leaf, root, and tuber extracts on the germination of the conidia of three saprobic fungi, viz., Curvalaria sp., Alternaria sp., and Helminthosporium sp. was tested. While the leaf exudate and tuber extracts slightly stimulated the germination of the conidia of the fungi, the leaf extract exerted a selective inhibitory effect on the germination of the conidia of Curvalaria sp., but not on the conidia of Helminthosporium sp. and Alternaria sp.", "contents": "Studies on the phyllosphere microflora of tapioca (Manihot utilissima Pohl). Studies on the phyllosphere microflora of tapioca (Manihot utilissima Pohl.) revealed that incidence of bacteria, fungi, and actinomycetes is indipendent of the variety, but dependent on the age. The bacteria and fungi increased with increasing age of the leaf and were more on mature leaves, whereas no such difference was noticed in the occurrence of actinomycetes. The large majority of the isolates, that were Gram-negative bacteria, was also amino acid-requiring. The chromogenic types occurred in greater abundance. The phyllosphere mycoflora consisted mainly of species of Asperigullus, Penicillium, Mucor, Curvularia, Alternaria, Helminthosporium, Fusarium, Hormicium, and Pullularia, at first three being predominant. There was no correlation between HCN content of leaves and microorganisms in the phyllosphere, Regarding the interrelationship between different groups of microorganisms in the phyllosphere, a positive correlation between fungi and actinomycetes and bacteria and actinomycetes in two (M. 4 and H. 105/44) varieties and a negative correlation for fungi and actinomycetes in one (H. 12/49) were obtained. The effect of leaf exudate and leaf, root, and tuber extracts on the germination of the conidia of three saprobic fungi, viz., Curvalaria sp., Alternaria sp., and Helminthosporium sp. was tested. While the leaf exudate and tuber extracts slightly stimulated the germination of the conidia of the fungi, the leaf extract exerted a selective inhibitory effect on the germination of the conidia of Curvalaria sp., but not on the conidia of Helminthosporium sp. and Alternaria sp."}
{"id": "PMID:189530", "title": "[Two malignant uterine tumors of embryonic tissue residues. (Carcinoma of Gartner's ducts, Mullerian mixed tumor)].", "content": "Report about a Gartnergang-carcinoma of the cervix uteri of a 24 years old woman. The cytological findings as well as the typical histological characteristics are represented. Persisting particles of the Gartnergang have been proved at the right lateral wall of the cervix uteri and in the lower parts of the corpus uteri. Report about a woman of 62 years. A Mullerian mixed tumour of the corpus uteri with myxoedematous parts has been diagnosed. It must be pointed out, that previous radiotherapy of the true pelvis may possible incluence the development of a Mullerian mixed tumour.", "contents": "[Two malignant uterine tumors of embryonic tissue residues. (Carcinoma of Gartner's ducts, Mullerian mixed tumor)]. Report about a Gartnergang-carcinoma of the cervix uteri of a 24 years old woman. The cytological findings as well as the typical histological characteristics are represented. Persisting particles of the Gartnergang have been proved at the right lateral wall of the cervix uteri and in the lower parts of the corpus uteri. Report about a woman of 62 years. A Mullerian mixed tumour of the corpus uteri with myxoedematous parts has been diagnosed. It must be pointed out, that previous radiotherapy of the true pelvis may possible incluence the development of a Mullerian mixed tumour."}
{"id": "PMID:189535", "title": "[Polyneuropathy in uremic patients in chronic hemodialysis (clinico-morphologic findings].", "content": "Among 50 patients who suffered from chronic renal insufficiency and who were on a chronic hemodialysis, 25 demonstrated uremic polyneuropathy with a different degree of expressiveness which depended upon the duration azotemia. A histological study of 13 postmortem cases detected a microfocal demyelinization in the peripheral nerves, and in cases of expressed pathology there were changes in the axon cast of the peripheral nerves and neurogenic muscular atrophy. There were no direct correlations between the development of polyneuropathy and the amount of hemodialysis sessions.", "contents": "[Polyneuropathy in uremic patients in chronic hemodialysis (clinico-morphologic findings]. Among 50 patients who suffered from chronic renal insufficiency and who were on a chronic hemodialysis, 25 demonstrated uremic polyneuropathy with a different degree of expressiveness which depended upon the duration azotemia. A histological study of 13 postmortem cases detected a microfocal demyelinization in the peripheral nerves, and in cases of expressed pathology there were changes in the axon cast of the peripheral nerves and neurogenic muscular atrophy. There were no direct correlations between the development of polyneuropathy and the amount of hemodialysis sessions."}
{"id": "PMID:189536", "title": "Studies on histones and nuclear phosphoproteins of rat liver and Morris hepatoma.", "content": "1. The chemical composition of chromatins obtained from Buffalo rat liver and Morris hepatoma strain 5123 was investigated. 2. The presence of an additional subfraction within the very lysine-rich histone (fl) was states in both kinds of tissues. It amounted to about 8% and 5% of fl in rat liver and Morris hepatoma, respectively. 3. Nuclear phosphoproteins (phenol-soluble) from normal and tumour tissues in polyacrylamide gel in SDS showed some qualitative differences in the range of molecular weights of about 40 000 - 70 000 and over 100 000 daltons.", "contents": "Studies on histones and nuclear phosphoproteins of rat liver and Morris hepatoma. 1. The chemical composition of chromatins obtained from Buffalo rat liver and Morris hepatoma strain 5123 was investigated. 2. The presence of an additional subfraction within the very lysine-rich histone (fl) was states in both kinds of tissues. It amounted to about 8% and 5% of fl in rat liver and Morris hepatoma, respectively. 3. Nuclear phosphoproteins (phenol-soluble) from normal and tumour tissues in polyacrylamide gel in SDS showed some qualitative differences in the range of molecular weights of about 40 000 - 70 000 and over 100 000 daltons."}
{"id": "PMID:189537", "title": "[Inhibition of the respiratory chain by the alkaloids berberine sulfate, alpinigenine, and tetrahydropalmatine].", "content": "The three alcaloids inhibited the NADH oxidase system of electron transfer particles from beef heart up to 90--100 percent. The concentrations of half-inhibition amounted to 50 muM for berberine sulphate and tetrahydropalmatine and 0.55 mM for alpinigenine. All three compounds showed comparable inhibitions on the succinate-cytochrome c oxidoreductase system only at concentrations 20--25 times as high. The site of action may be the iron sulphur region of the complex I of the electron transfer system. The biological importance of this respiratory inhibitions should be taken into account.", "contents": "[Inhibition of the respiratory chain by the alkaloids berberine sulfate, alpinigenine, and tetrahydropalmatine]. The three alcaloids inhibited the NADH oxidase system of electron transfer particles from beef heart up to 90--100 percent. The concentrations of half-inhibition amounted to 50 muM for berberine sulphate and tetrahydropalmatine and 0.55 mM for alpinigenine. All three compounds showed comparable inhibitions on the succinate-cytochrome c oxidoreductase system only at concentrations 20--25 times as high. The site of action may be the iron sulphur region of the complex I of the electron transfer system. The biological importance of this respiratory inhibitions should be taken into account."}
{"id": "PMID:189538", "title": "[Hormonal stimulation of adenosine 3',5'-cyclic monophosphate formation in cell-free particles and intact cells of smooth muscle in the aorta and femoral artery of rats during immubilization stress].", "content": "The ability of adrenaline and histamine to stimulate the formation of cyclic AMP was investigated in broken cell preparation and intact cells of smooth muscle of the aorta and femoral artery of rats which had been subjected to daily intermittent immobilization for 1, 3, and 17 weeks. It was found that this type of stress led to an instability of the blood pressure which was associated with an increase in the sensitivity of adenylate cyclase in the broken cell preparations from the arteries to adrenaline and histamine and with a heightened cyclic AMP response to the two hormones in the intact arterial smooth muscle cells. The sensitivity of cardiac adenylate cyclase for adrenaline remained unchanged.", "contents": "[Hormonal stimulation of adenosine 3',5'-cyclic monophosphate formation in cell-free particles and intact cells of smooth muscle in the aorta and femoral artery of rats during immubilization stress]. The ability of adrenaline and histamine to stimulate the formation of cyclic AMP was investigated in broken cell preparation and intact cells of smooth muscle of the aorta and femoral artery of rats which had been subjected to daily intermittent immobilization for 1, 3, and 17 weeks. It was found that this type of stress led to an instability of the blood pressure which was associated with an increase in the sensitivity of adenylate cyclase in the broken cell preparations from the arteries to adrenaline and histamine and with a heightened cyclic AMP response to the two hormones in the intact arterial smooth muscle cells. The sensitivity of cardiac adenylate cyclase for adrenaline remained unchanged."}
{"id": "PMID:189539", "title": "Antagonism by guanosine 3',5'-cyclic monophosphate derivatives against the action of adrenaline on the automaticity of isolated rat heart muscle cells in culture.", "content": "Spontaneously and rhythmically beating single cells from the ventricles of new-born rats were cultured on coverslips for 3 to 4 days and transferred to a small perfusion chamber for photoelectric recording of their contractions. The cells responded to 3 - 10(-7) M adrenaline with a pronounced increase and to 1.7 - 10(-5) M carbamylcholine with a mode-rate decrease in the rate of beat. Carbamylcholine nearly abolished the beat-accelerating effect of adrenaline. 8-Bromo cyclic GMP and N2-2'-O-'DIBUTYRYL CYCLIC GMP, in concentrations of 4.2 to 8.4 - 10(-4) M, exerted only very slight depressant effects on the basal rate of beat, but strongly antagonized, and in the majority of experiments with 8-bromo cyclic GMP completely suppressed, the positive chronotropic action of adrenaline. Cyclic GMP, 5'-GMP, and 5'-guanylylimidodiphosphate were without effect. 8-Bromo cyclic AMP caused a marked acceleration of beating. In view of the mediator roles that cyclic AMP and cyclic GMP have been assigned in the cardiac actions of beta-adrenergic and of cholinergic agents, respectively, the present results may be interpreted as being indicative of an adrenergic-cholinergic antagonism at the level of these two cyclic nucleotides.", "contents": "Antagonism by guanosine 3',5'-cyclic monophosphate derivatives against the action of adrenaline on the automaticity of isolated rat heart muscle cells in culture. Spontaneously and rhythmically beating single cells from the ventricles of new-born rats were cultured on coverslips for 3 to 4 days and transferred to a small perfusion chamber for photoelectric recording of their contractions. The cells responded to 3 - 10(-7) M adrenaline with a pronounced increase and to 1.7 - 10(-5) M carbamylcholine with a mode-rate decrease in the rate of beat. Carbamylcholine nearly abolished the beat-accelerating effect of adrenaline. 8-Bromo cyclic GMP and N2-2'-O-'DIBUTYRYL CYCLIC GMP, in concentrations of 4.2 to 8.4 - 10(-4) M, exerted only very slight depressant effects on the basal rate of beat, but strongly antagonized, and in the majority of experiments with 8-bromo cyclic GMP completely suppressed, the positive chronotropic action of adrenaline. Cyclic GMP, 5'-GMP, and 5'-guanylylimidodiphosphate were without effect. 8-Bromo cyclic AMP caused a marked acceleration of beating. In view of the mediator roles that cyclic AMP and cyclic GMP have been assigned in the cardiac actions of beta-adrenergic and of cholinergic agents, respectively, the present results may be interpreted as being indicative of an adrenergic-cholinergic antagonism at the level of these two cyclic nucleotides."}
{"id": "PMID:189540", "title": "[Mediastinal chemodectoma (author's transl)].", "content": "In 1958 a mediastinal tumor was discovered in an asymptomatic patient. She had previously complained of vomiting and an oesophageal abnormality had been discovered though not treated. The mediastinal tumor was resected and diagnosed as a non chromaffine chemodectoma. In the follow-up the mediastinal image never appeared normal and the heart shadow was enlarged. In 1974 an infiltrate appeared in the left lung. In 1975 the patient was operated : a pulmonary osteochondroma, a pericarditis and an intrapericardial aortopulmonary chemodectoma were discovered. The mediastinal chemodectoma is a rare tumor and its frequency, location and signs are discussed. The importance of angiography for diagnosis is stressed. The authors consider malignant degenerescence to be rare, and the treatment is surgical as the tumor is radioresistant. In the present case there was either a malignant recurrence or multiple focuses with a possible oesophageal location.", "contents": "[Mediastinal chemodectoma (author's transl)]. In 1958 a mediastinal tumor was discovered in an asymptomatic patient. She had previously complained of vomiting and an oesophageal abnormality had been discovered though not treated. The mediastinal tumor was resected and diagnosed as a non chromaffine chemodectoma. In the follow-up the mediastinal image never appeared normal and the heart shadow was enlarged. In 1974 an infiltrate appeared in the left lung. In 1975 the patient was operated : a pulmonary osteochondroma, a pericarditis and an intrapericardial aortopulmonary chemodectoma were discovered. The mediastinal chemodectoma is a rare tumor and its frequency, location and signs are discussed. The importance of angiography for diagnosis is stressed. The authors consider malignant degenerescence to be rare, and the treatment is surgical as the tumor is radioresistant. In the present case there was either a malignant recurrence or multiple focuses with a possible oesophageal location."}
{"id": "PMID:189541", "title": "Adenovirus infection of the cervix.", "content": "A case is recorded in which intranuclear inclusions suggesting adenovirus infection were recognized in a routine Papanicolaou smear. The patient was recalled for virologic studies and adenovirus type 19 was cultured from the cervix. The patient had a recent history of systemic illness with conjunctivitis, and a friend had conjunctivitis at the same time which was also proven to be due to adenovirus of the same serotype. This is the first reported instance in which adenovirus infection of the cervix suspected on cytologic findings has been confirmed by virus culture.", "contents": "Adenovirus infection of the cervix. A case is recorded in which intranuclear inclusions suggesting adenovirus infection were recognized in a routine Papanicolaou smear. The patient was recalled for virologic studies and adenovirus type 19 was cultured from the cervix. The patient had a recent history of systemic illness with conjunctivitis, and a friend had conjunctivitis at the same time which was also proven to be due to adenovirus of the same serotype. This is the first reported instance in which adenovirus infection of the cervix suspected on cytologic findings has been confirmed by virus culture."}
{"id": "PMID:189543", "title": "A behavior of Y chromatin in cancer cells of males.", "content": "Y-chromatin or Y-body which is present in interphase nuclei in over 78 per cent of somatic male cells varied in frequency and multiplication in malignant tumors. The variation is characteristic of each tumor and kept fairly constant in cultured cell lines unless modulation occurs during continuous subcultures. The variation was due to chromosomal abnormality, aneuploidization or polyploidization, but in part appears to be related to abnormality of intercalary quinacrine binding to chromosomes.", "contents": "A behavior of Y chromatin in cancer cells of males. Y-chromatin or Y-body which is present in interphase nuclei in over 78 per cent of somatic male cells varied in frequency and multiplication in malignant tumors. The variation is characteristic of each tumor and kept fairly constant in cultured cell lines unless modulation occurs during continuous subcultures. The variation was due to chromosomal abnormality, aneuploidization or polyploidization, but in part appears to be related to abnormality of intercalary quinacrine binding to chromosomes."}
{"id": "PMID:189548", "title": "Action of cyclic nucleotides on protein and RNA synthesis in the thyroid.", "content": "Thyrotrophin (TSH) regulates the biosynthesis of thyroid protein and RNA. This action is mediated by adenylate cyclase and cycl AMP. In the present study the action of cyclic GMP and cyclic CMP was investigated in beef slices. Both cyclic AMP and cyclic GMP significantly increased the incorporation of [3H]uridine into RNA. These effects were blocked by actinomycin D, suggesting that their action is located at a preor at a transcriptional step. The PCA soluble fraction radioactivity followed in parallel with tha variations observed in the RNA fraction, supporting the view that cyclic nucleotides may regulate RNA by modulating the nucleotide precursors pool. Cyclic CMP in concentrations between 0.35 to 1.5 mM progressively decreased the RNA labelling, and the values of the PCA soluble radioactivity again followed  those of RNA. Furthermore, cyclic CMP also blocked the in vitro stimulatory action of cyclic AMP on the incorporation of [3H]leucine into protein, and of [3H]uridine into RNA. The present results provide the first information on the action of cyclic AMP on RNA synthesis and suggest that negative signals may also play a part in the regulation of thyroid function.", "contents": "Action of cyclic nucleotides on protein and RNA synthesis in the thyroid. Thyrotrophin (TSH) regulates the biosynthesis of thyroid protein and RNA. This action is mediated by adenylate cyclase and cycl AMP. In the present study the action of cyclic GMP and cyclic CMP was investigated in beef slices. Both cyclic AMP and cyclic GMP significantly increased the incorporation of [3H]uridine into RNA. These effects were blocked by actinomycin D, suggesting that their action is located at a preor at a transcriptional step. The PCA soluble fraction radioactivity followed in parallel with tha variations observed in the RNA fraction, supporting the view that cyclic nucleotides may regulate RNA by modulating the nucleotide precursors pool. Cyclic CMP in concentrations between 0.35 to 1.5 mM progressively decreased the RNA labelling, and the values of the PCA soluble radioactivity again followed  those of RNA. Furthermore, cyclic CMP also blocked the in vitro stimulatory action of cyclic AMP on the incorporation of [3H]leucine into protein, and of [3H]uridine into RNA. The present results provide the first information on the action of cyclic AMP on RNA synthesis and suggest that negative signals may also play a part in the regulation of thyroid function."}
{"id": "PMID:189544", "title": "Use of the cytocentrifuge for the detection of cytomegalovirus inclusions in the urine of renal allograft patients. A case roport.", "content": "The cytodiagnosis of virus infected cells in the urine of immunosuppressed patients is a new and important aspect of exfoliative cytology. A case report is presented which demonstrates the detection of diagnostic viral inclusions in a renal allograft recipient with CID. Diagnostic cells with good cytologic detail are observed using a Cytocentrifuge technique.", "contents": "Use of the cytocentrifuge for the detection of cytomegalovirus inclusions in the urine of renal allograft patients. A case roport. The cytodiagnosis of virus infected cells in the urine of immunosuppressed patients is a new and important aspect of exfoliative cytology. A case report is presented which demonstrates the detection of diagnostic viral inclusions in a renal allograft recipient with CID. Diagnostic cells with good cytologic detail are observed using a Cytocentrifuge technique."}
{"id": "PMID:189549", "title": "The effect of pituitary-adrenal manipulations upon urinary cyclic AMP excretion in man.", "content": "The present studies demonstrate that the administration of pharmacologic amounts of ACTH is associated with small but significant increases in urinary cyclic AMP excretion and in urinary cyclic AMP/creatinine ratios which are most likely related to a release of cyclic AMP from adrenocortical tissue. Acute suppression of the pituitary-adrenal axis with dexamethasone and stimulation with metyrapone, however, is not associated with changes in urinary cyclic AMP excretion. These results suggest that physiological levels of ACTH and cortisol contribute little, if any, to the urinary excretion of cyclic AMP in man.", "contents": "The effect of pituitary-adrenal manipulations upon urinary cyclic AMP excretion in man. The present studies demonstrate that the administration of pharmacologic amounts of ACTH is associated with small but significant increases in urinary cyclic AMP excretion and in urinary cyclic AMP/creatinine ratios which are most likely related to a release of cyclic AMP from adrenocortical tissue. Acute suppression of the pituitary-adrenal axis with dexamethasone and stimulation with metyrapone, however, is not associated with changes in urinary cyclic AMP excretion. These results suggest that physiological levels of ACTH and cortisol contribute little, if any, to the urinary excretion of cyclic AMP in man."}
{"id": "PMID:189550", "title": "Cortisol and corticosterone productions of isolated adrenal cells in neonatal rabbits.", "content": "Isolated adrenal cells of rabbits aged from 0 h to day 40 after birth were incubated for 2 h in the presence of ACTH. Thin-layer chromatography and the fluorimetric method were used to evaluate the products of these adrenal cells separately for cortisol and corticosterone. Cortisol production by adrenal cells in response to ACTH (0.1 mU) was found to be highest between 0 and 8 h after birth (0.522 +/- 0.049 mug/105 cells; mean +/- SEM). A decrease was observed at 9-20 h and this was further followed by a steady decrease up to day 35-40. Corticosterone production was 0.206 +/- 0.042 mug/105 cells between 0 and 8 h after birth. Subsequently, this level was evenly maintained up to 12-14, but it tended to increase on day 35-40. The level of cortisol production was significantly higher than that of corticosterone production at 0-20 h after birth, while the former was significantly lower than the latter from day 12-14 onwards. The ratio of corticosterone to total corticosteroids (cortisol +  corticosterone) was very low (0.28 +/- 0.04) at 0-8 h after birth, but showed a progressive rise up to day 35-40, when it was 0.95 +/- 0.01. The results of the present study show that cortisol is the pre-dominant product of the adrenal cells in rabbits during early post-natal life.", "contents": "Cortisol and corticosterone productions of isolated adrenal cells in neonatal rabbits. Isolated adrenal cells of rabbits aged from 0 h to day 40 after birth were incubated for 2 h in the presence of ACTH. Thin-layer chromatography and the fluorimetric method were used to evaluate the products of these adrenal cells separately for cortisol and corticosterone. Cortisol production by adrenal cells in response to ACTH (0.1 mU) was found to be highest between 0 and 8 h after birth (0.522 +/- 0.049 mug/105 cells; mean +/- SEM). A decrease was observed at 9-20 h and this was further followed by a steady decrease up to day 35-40. Corticosterone production was 0.206 +/- 0.042 mug/105 cells between 0 and 8 h after birth. Subsequently, this level was evenly maintained up to 12-14, but it tended to increase on day 35-40. The level of cortisol production was significantly higher than that of corticosterone production at 0-20 h after birth, while the former was significantly lower than the latter from day 12-14 onwards. The ratio of corticosterone to total corticosteroids (cortisol +  corticosterone) was very low (0.28 +/- 0.04) at 0-8 h after birth, but showed a progressive rise up to day 35-40, when it was 0.95 +/- 0.01. The results of the present study show that cortisol is the pre-dominant product of the adrenal cells in rabbits during early post-natal life."}
{"id": "PMID:189546", "title": "Virus infections of the respiratory tract cytopathologic and clinical analysis.", "content": "Thirty-three cases of respiratory tract virus infections diagnosed cytologically are reviewed. The clinical and demographic data are presented and correlated with an analysis of the cytologic findings. Herpes virus was the most common infection. It occurred in patients with other severe medical problems and had little apparent effect on the clinical outcome of any particular case. Quantitative and qualitative cytologic findings did not correlate with the severity of the herpetic infection. The virus was isolated in culture in only one of 21 cases of Herpes virus infection. Cases in the later part of the study indicate an increasing incidence or recognition of the infection in the respiratory tract. In this series there was a clustering of Herpes virus cases in relation to date of admission and hospitalization in respiratory intensive care. Cytomegalovirus infection was recognized in four cases. This infection occurs in the immune suppressed patient and can be made reliably from cytologic findings. Smears must be screened thoroughly and carefully as the characteristic inclusion is seen in only a rare cell. Bronchial brushing specimens are the most useful. The disease should not be fatal if the level of immune suppression can be manipulated and the patients basic medical problem is not too severe. Cytologic findings contribute little information to tjor medical problems and the adenovirus infection was incidental. Thy cytologic findings in some cases may be non-specific since antibody studies and culteral confirmation are lacking in these cases.", "contents": "Virus infections of the respiratory tract cytopathologic and clinical analysis. Thirty-three cases of respiratory tract virus infections diagnosed cytologically are reviewed. The clinical and demographic data are presented and correlated with an analysis of the cytologic findings. Herpes virus was the most common infection. It occurred in patients with other severe medical problems and had little apparent effect on the clinical outcome of any particular case. Quantitative and qualitative cytologic findings did not correlate with the severity of the herpetic infection. The virus was isolated in culture in only one of 21 cases of Herpes virus infection. Cases in the later part of the study indicate an increasing incidence or recognition of the infection in the respiratory tract. In this series there was a clustering of Herpes virus cases in relation to date of admission and hospitalization in respiratory intensive care. Cytomegalovirus infection was recognized in four cases. This infection occurs in the immune suppressed patient and can be made reliably from cytologic findings. Smears must be screened thoroughly and carefully as the characteristic inclusion is seen in only a rare cell. Bronchial brushing specimens are the most useful. The disease should not be fatal if the level of immune suppression can be manipulated and the patients basic medical problem is not too severe. Cytologic findings contribute little information to tjor medical problems and the adenovirus infection was incidental. Thy cytologic findings in some cases may be non-specific since antibody studies and culteral confirmation are lacking in these cases."}
{"id": "PMID:189551", "title": "FSH: II. Evidence for its mediating role on testosterone secretion in hypopituitarism.", "content": "Testicular responses to administration of human chorionic gonadotrophin (HCG) in 23 hypopituitary patients were compared to responses obtained in adequate control groups and correlated to basal plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. Sixteen nonpubertal patients demonstrated a significantly diminished testosterone response (250 +/- 64 ng/100 ml, mean +/- SEM) along with low basal plasma FSH values (1.4 +/- 0.2 mU/ml) when compared to normal response (607 +/- 97 ng/100 ml) and normal FSH level (2.3 +/- 0.2 mU/ml), but with normal LH values. In 7 pubertal patients decreased testosterone responses to HCG (815 +/- 147 ng/100 ml) were observed with normal plasma FSH and LH values. Correlation between testosterone responses and FSH levels (r - 0.718, P less than 0.002) in the pre-pubertal hypopituitary patients was highly significant. No such correlation was observed between testosterone response and LH. The represent findings may a) give one explanation for the absence of response to HCG observed in some cases of hypopituitarism, b) give support to the hypothesis that FSH has a mediating role on LH-induced secretion of testosterone by the testis in human subjects.", "contents": "FSH: II. Evidence for its mediating role on testosterone secretion in hypopituitarism. Testicular responses to administration of human chorionic gonadotrophin (HCG) in 23 hypopituitary patients were compared to responses obtained in adequate control groups and correlated to basal plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. Sixteen nonpubertal patients demonstrated a significantly diminished testosterone response (250 +/- 64 ng/100 ml, mean +/- SEM) along with low basal plasma FSH values (1.4 +/- 0.2 mU/ml) when compared to normal response (607 +/- 97 ng/100 ml) and normal FSH level (2.3 +/- 0.2 mU/ml), but with normal LH values. In 7 pubertal patients decreased testosterone responses to HCG (815 +/- 147 ng/100 ml) were observed with normal plasma FSH and LH values. Correlation between testosterone responses and FSH levels (r - 0.718, P less than 0.002) in the pre-pubertal hypopituitary patients was highly significant. No such correlation was observed between testosterone response and LH. The represent findings may a) give one explanation for the absence of response to HCG observed in some cases of hypopituitarism, b) give support to the hypothesis that FSH has a mediating role on LH-induced secretion of testosterone by the testis in human subjects."}
{"id": "PMID:189552", "title": "Localization of prolactin binding in prostate and testis: The role of serum prolactin concentration on the testicular LH receptor.", "content": "Specific binding sites for prolactin (PRL) and gonadotrophins on ventral and dorsolateral prostate as well as on Leydig cells and tubules of testes of rats at different ages were examined. The binding sites for PRL were found in greatest number in ventral prostate and in Leydig cells. LH binding sites were also more numerous than FSH binding sites in the latter. FSH sites were greater than LH sites in tubular preparations obtained from the testis. Specific binding (SB) of PRL in the Leydig cells reached a maximum at 45 days (4%) and in the case of LH a maximum of 12% was obtained at 70 days. In both preparations SB of FSH exhibited a plateau between 20 and 40 days (11%) followed by a gradual decline to 6% at 100 days. Following 20 dyas of treatment with Bromocriptin beginning at 20 days serum PRL was suppressed and SB of LH to the Leydig cells was significantly decreased, whereas SB of PRL and FSH was unaffected. These studies suggest that despite decreases in serum PRL, the number of PRL and FSH receptors remain unaltered. On the contrary, LH receptors in the rat testis are modulated by changes in serum PRL.", "contents": "Localization of prolactin binding in prostate and testis: The role of serum prolactin concentration on the testicular LH receptor. Specific binding sites for prolactin (PRL) and gonadotrophins on ventral and dorsolateral prostate as well as on Leydig cells and tubules of testes of rats at different ages were examined. The binding sites for PRL were found in greatest number in ventral prostate and in Leydig cells. LH binding sites were also more numerous than FSH binding sites in the latter. FSH sites were greater than LH sites in tubular preparations obtained from the testis. Specific binding (SB) of PRL in the Leydig cells reached a maximum at 45 days (4%) and in the case of LH a maximum of 12% was obtained at 70 days. In both preparations SB of FSH exhibited a plateau between 20 and 40 days (11%) followed by a gradual decline to 6% at 100 days. Following 20 dyas of treatment with Bromocriptin beginning at 20 days serum PRL was suppressed and SB of LH to the Leydig cells was significantly decreased, whereas SB of PRL and FSH was unaffected. These studies suggest that despite decreases in serum PRL, the number of PRL and FSH receptors remain unaltered. On the contrary, LH receptors in the rat testis are modulated by changes in serum PRL."}
{"id": "PMID:189547", "title": "Scanning electron microscopy in the study of lung cancer. New technique of comparative studies on the same lung cancer cells by light microscopy and scanning electron microscopy.", "content": "A new technique for observing the same lung cancer cells by light microscope and SEM was developed. By this technique it was clarified that the surface ultrastructures of epidermoid carcinoma, adenocarcinoma and oat-cell carcinoma cells are different from each other. Those of adenocarcinoma and mesothelial cells were quite different. This technique might be of use, adding new information into the ordinary cytologic diagnosis of cancer cells.", "contents": "Scanning electron microscopy in the study of lung cancer. New technique of comparative studies on the same lung cancer cells by light microscopy and scanning electron microscopy. A new technique for observing the same lung cancer cells by light microscope and SEM was developed. By this technique it was clarified that the surface ultrastructures of epidermoid carcinoma, adenocarcinoma and oat-cell carcinoma cells are different from each other. Those of adenocarcinoma and mesothelial cells were quite different. This technique might be of use, adding new information into the ordinary cytologic diagnosis of cancer cells."}
{"id": "PMID:189553", "title": "Prostaglandin mediated natriuresis during glucagon infusion in dogs.", "content": "Ten mug/min glucagon infused intravenously for 30 min in conscious dogs (weight 15-25 kg) is shown to increase renal prostaglandin activity and to produce a natriuretic effect, which is impaired by indomethacin pretreatment. Cardiac output, heart rate, renal blood flow and urine cAMP excretion are similarly increases in non-pre-treated and indomethacin pre-treated dogs. Glucagon infusion does not consistently change plasma renin activity in non-pre-treated dogs, while the renin secretion is almost totally blocked when glucagon is administered to dogs that are pre-treated with indomethacin. The results are consistent with the view that the natriuretic response to glucagon is largley dependent upon increased renal blood flow. An addition tubular prostaglandin mediated and possible anti-aldosterone effect is, however, also involved.", "contents": "Prostaglandin mediated natriuresis during glucagon infusion in dogs. Ten mug/min glucagon infused intravenously for 30 min in conscious dogs (weight 15-25 kg) is shown to increase renal prostaglandin activity and to produce a natriuretic effect, which is impaired by indomethacin pretreatment. Cardiac output, heart rate, renal blood flow and urine cAMP excretion are similarly increases in non-pre-treated and indomethacin pre-treated dogs. Glucagon infusion does not consistently change plasma renin activity in non-pre-treated dogs, while the renin secretion is almost totally blocked when glucagon is administered to dogs that are pre-treated with indomethacin. The results are consistent with the view that the natriuretic response to glucagon is largley dependent upon increased renal blood flow. An addition tubular prostaglandin mediated and possible anti-aldosterone effect is, however, also involved."}
{"id": "PMID:189554", "title": "Binding of cholecalciferol metabolites to rat duodenal mucosa cytosol.", "content": "In vitro binding of 25-hydroxycholecalciferol (25-(OH)D3) and 1alpha,25-dihydroxycholecalciferol (1,25-(OH)2D3) was studied in the duodenal mucosa cytosol of rachitic rats: both 25-(OH)D3 and 1,25-(OH)2D3 bind to a macromolecule (sedimentation coefficient 5.5 to 6 S in low or high ionic strength) with a high affinity (KD at 4 degrees C = 1.2 X 10-9M and 2 x 10-9M, respectively). In addition, it is concluded from competition and chase experiments that 25-(OH)D3 binding sites differ from that for 1,25-(OH)2D3.", "contents": "Binding of cholecalciferol metabolites to rat duodenal mucosa cytosol. In vitro binding of 25-hydroxycholecalciferol (25-(OH)D3) and 1alpha,25-dihydroxycholecalciferol (1,25-(OH)2D3) was studied in the duodenal mucosa cytosol of rachitic rats: both 25-(OH)D3 and 1,25-(OH)2D3 bind to a macromolecule (sedimentation coefficient 5.5 to 6 S in low or high ionic strength) with a high affinity (KD at 4 degrees C = 1.2 X 10-9M and 2 x 10-9M, respectively). In addition, it is concluded from competition and chase experiments that 25-(OH)D3 binding sites differ from that for 1,25-(OH)2D3."}
{"id": "PMID:189555", "title": "Distribution of glucose-6-phosphatase and 5-nucleotidase in the digestive system of two teleost fishes.", "content": "The distribution and histochemical localization of G6Pase and 5-nucleotidase in the different parts of the alimentary canal of two teleost fishes, Heteropneustes fossilis and Barbus sophore have been studied. The major sites of activity of the two enzymes are intestinal mucosa and liver. G6Pase is localized in the cytoplasm of the absorptive cells of the intestinal mucosa while 5-nucleotidase is present in the cytoplasm as well as nucleus and cell membrane. In the intestine, the anterior portion shows more stronger activity than in the middle and posterior portions. Mild activity is also noticed in the mucosa and gastric glands of the stomach. G6Pase activity is stronger than 5-nucleotidase activity in all the portions. Weak 5-nucleotidase activity is found in the submucosal connective tissue and the nuclei of the intestine. The goblet cells, muscularis abd serosa are negative in all the portions. G6Pase activity is stronger in the herbivorous fish Barbus sophore than in the omnivorous form Heteropneustes fossilis. In the liver, stronger activity of two enzymes is localized in the hepatocytes surrounding the sinusoids. Connective tissue and endothelial lining are negative.", "contents": "Distribution of glucose-6-phosphatase and 5-nucleotidase in the digestive system of two teleost fishes. The distribution and histochemical localization of G6Pase and 5-nucleotidase in the different parts of the alimentary canal of two teleost fishes, Heteropneustes fossilis and Barbus sophore have been studied. The major sites of activity of the two enzymes are intestinal mucosa and liver. G6Pase is localized in the cytoplasm of the absorptive cells of the intestinal mucosa while 5-nucleotidase is present in the cytoplasm as well as nucleus and cell membrane. In the intestine, the anterior portion shows more stronger activity than in the middle and posterior portions. Mild activity is also noticed in the mucosa and gastric glands of the stomach. G6Pase activity is stronger than 5-nucleotidase activity in all the portions. Weak 5-nucleotidase activity is found in the submucosal connective tissue and the nuclei of the intestine. The goblet cells, muscularis abd serosa are negative in all the portions. G6Pase activity is stronger in the herbivorous fish Barbus sophore than in the omnivorous form Heteropneustes fossilis. In the liver, stronger activity of two enzymes is localized in the hepatocytes surrounding the sinusoids. Connective tissue and endothelial lining are negative."}
{"id": "PMID:189556", "title": "[Enzyme histochemistry of the sand rat pancreas (Psammomys obesus) after different caloric food].", "content": "In a complex investigation were evidenced 12 selected enzymes (oxidoreductases and hydrolases) in the pancreas of normoglycemic sand rats (Psammomys obesus). The sand rat developed a spontaneous diabetic metabolism by holding in the vivarium. The material based of animal groups that were fooded ad libitum or after defined dietetic regimes. The topochemical pattern of enzymes in the Langerhans' islets and exocrine acini can be compared between the sand rat groups and with the good investigated model of the Wistar rat. Because enzymhistochemical investigations of the sand rat pancreas absented, were the results compared with the rare specific observations of other animals and the man and the changed metabolic level were discussed under the especially food situation and in diabetes mellitus.", "contents": "[Enzyme histochemistry of the sand rat pancreas (Psammomys obesus) after different caloric food]. In a complex investigation were evidenced 12 selected enzymes (oxidoreductases and hydrolases) in the pancreas of normoglycemic sand rats (Psammomys obesus). The sand rat developed a spontaneous diabetic metabolism by holding in the vivarium. The material based of animal groups that were fooded ad libitum or after defined dietetic regimes. The topochemical pattern of enzymes in the Langerhans' islets and exocrine acini can be compared between the sand rat groups and with the good investigated model of the Wistar rat. Because enzymhistochemical investigations of the sand rat pancreas absented, were the results compared with the rare specific observations of other animals and the man and the changed metabolic level were discussed under the especially food situation and in diabetes mellitus."}
{"id": "PMID:189557", "title": "\"PKU bodies\": characteristic inclusions in the brain in phenylketonuria.", "content": "The ultrastructure of various inclusions within oligodendroglial cells in the brains from two phenylketonuric patients was studied. Characteristic lamellar, oval, slightly irregular inclusions measured between 0.5 and 2 micra in diameter and were bounded by a single membrane. The longitudinal and transverse lamellae of these inclusions had a distinct pattern. In analogy to lamellated but different inclusions of other diseases, these structures were termed \"PKU bodies\". Various possibilities that would explain the morphogenesis of the PKU bodies and other inclusions in the oligodendroglial cells, and the significance of these findings, are discussed.", "contents": "\"PKU bodies\": characteristic inclusions in the brain in phenylketonuria. The ultrastructure of various inclusions within oligodendroglial cells in the brains from two phenylketonuric patients was studied. Characteristic lamellar, oval, slightly irregular inclusions measured between 0.5 and 2 micra in diameter and were bounded by a single membrane. The longitudinal and transverse lamellae of these inclusions had a distinct pattern. In analogy to lamellated but different inclusions of other diseases, these structures were termed \"PKU bodies\". Various possibilities that would explain the morphogenesis of the PKU bodies and other inclusions in the oligodendroglial cells, and the significance of these findings, are discussed."}
{"id": "PMID:189558", "title": "Lymphocyte inclusions in the juvenile type of generalized ceroid-lipofuscinosis. An electron microscopic study.", "content": "Peripheral blood lymphocytes exhibiting cytoplasmic vacuoles from eight patients with the juvenile type of generalized ceroid-lipofuscinosis were investigated by electron microscopy. Osmiophilic inclusions could be demonstrated in the vacuoles and occasionally in the cytoplasm proper, revealing a fingerprint-like ultrastructural pattern or a less defined dense granular material, sometimes with an osmiophobic component adjoined. The inclusions are compared with those demonstrated in seven of the cases by earlier investigations of rectal biopsies in a variety of cell types, mainly in nerve cells. Discrimination is attempted between the lymphocyte inclusions and \"parallel tubular arrays\" regarded as representing a regular lymphocyte constituent.", "contents": "Lymphocyte inclusions in the juvenile type of generalized ceroid-lipofuscinosis. An electron microscopic study. Peripheral blood lymphocytes exhibiting cytoplasmic vacuoles from eight patients with the juvenile type of generalized ceroid-lipofuscinosis were investigated by electron microscopy. Osmiophilic inclusions could be demonstrated in the vacuoles and occasionally in the cytoplasm proper, revealing a fingerprint-like ultrastructural pattern or a less defined dense granular material, sometimes with an osmiophobic component adjoined. The inclusions are compared with those demonstrated in seven of the cases by earlier investigations of rectal biopsies in a variety of cell types, mainly in nerve cells. Discrimination is attempted between the lymphocyte inclusions and \"parallel tubular arrays\" regarded as representing a regular lymphocyte constituent."}
{"id": "PMID:189559", "title": "The protracted form of juvenile neuronal ceroid-lipofuscinosis.", "content": "Clinical and ultrastructural findings consisting of curvilinear and fingerprint residual bodies, in a protracted juvenile form of NCL are reported from a woman who died at the age of 35 years. Homochrony and homotypy of her brother's illness emphasize intrafamilial similarities within subgroups of lysosomal disorders.", "contents": "The protracted form of juvenile neuronal ceroid-lipofuscinosis. Clinical and ultrastructural findings consisting of curvilinear and fingerprint residual bodies, in a protracted juvenile form of NCL are reported from a woman who died at the age of 35 years. Homochrony and homotypy of her brother's illness emphasize intrafamilial similarities within subgroups of lysosomal disorders."}
{"id": "PMID:189561", "title": "Atlanto-axial fusion in rheumatoid arthritis. A new method of fixation with wire and bone cement.", "content": "Twenty-eight occipito-cervical fusions performed over the past 4 years in patients with rheumatoid arthritis are discussed. All of the patients with one exception had signs of neurological involvement preoperatively due to pressure on occipital nerve roots, spinal cord and/or vertebral arteries. A surgical technique using wire, pin and bone cement and permitting early mobilization without external fixation was used and is described in detail. The clinical results were excellent in 21 cases with an additional five patients showing improvement. One patient did not benefit from surgery and one had no symptoms preoperatively. The results are encouraging and the possibility of early mobilization (the day after surgery) is of the utmost importance for this group of patients.", "contents": "Atlanto-axial fusion in rheumatoid arthritis. A new method of fixation with wire and bone cement. Twenty-eight occipito-cervical fusions performed over the past 4 years in patients with rheumatoid arthritis are discussed. All of the patients with one exception had signs of neurological involvement preoperatively due to pressure on occipital nerve roots, spinal cord and/or vertebral arteries. A surgical technique using wire, pin and bone cement and permitting early mobilization without external fixation was used and is described in detail. The clinical results were excellent in 21 cases with an additional five patients showing improvement. One patient did not benefit from surgery and one had no symptoms preoperatively. The results are encouraging and the possibility of early mobilization (the day after surgery) is of the utmost importance for this group of patients."}
{"id": "PMID:189565", "title": "A study on Mallory bodies. Isolation, ultrastructure and preliminary biochemical characterization of Mallory bodies from livers of alcoholic cirrhosis and malignant hepatoma.", "content": "Mallory bodies (MBs) were isolated from the livers of 8 alcoholic patients and a malignant hepatoma occurring in a non-alcoholic patient. MBs were isolated in large quantity and high purity. The isolates were devoid of liver cell organelles except in the case of malignant hepatoma where dense and membranous material resembling nuclear substances and endoplasmic reticulum were found. The \"nuclear\" material had continuity with MBs. Electron microscopic examination suggested the presence of a dense body and very fine filaments within in situ and isolated MBs in addition to the tubular structure of so-called MB fibers. Amino acid analysis indicated that the major component of MBs is a protein which does not contain unusual amino acids or any particular amino acid in a large quantity to characterize this protein. The isolated fractions were solubilized in 6 M guaindine hydrochloride by sonication or in 1% sodium dodecyl sulfate (SDS) with 2 mercaptoethanol and 8 M urea. The solubilized MB protein produced 3 peaks by Sephadex G 100 chromatography and at least five intense protein bands by SDS polyacrylamide gel electrophoresis. Serum sample and the fractions from control livers contained several protein bands which were similar to the major components of isolated MB protein. These morphological and biochemical findings suggest that MBs are not homogeneous protein, but they are probably complexes of various proteins and that some components of MBs are present in normal hepatocytes.", "contents": "A study on Mallory bodies. Isolation, ultrastructure and preliminary biochemical characterization of Mallory bodies from livers of alcoholic cirrhosis and malignant hepatoma. Mallory bodies (MBs) were isolated from the livers of 8 alcoholic patients and a malignant hepatoma occurring in a non-alcoholic patient. MBs were isolated in large quantity and high purity. The isolates were devoid of liver cell organelles except in the case of malignant hepatoma where dense and membranous material resembling nuclear substances and endoplasmic reticulum were found. The \"nuclear\" material had continuity with MBs. Electron microscopic examination suggested the presence of a dense body and very fine filaments within in situ and isolated MBs in addition to the tubular structure of so-called MB fibers. Amino acid analysis indicated that the major component of MBs is a protein which does not contain unusual amino acids or any particular amino acid in a large quantity to characterize this protein. The isolated fractions were solubilized in 6 M guaindine hydrochloride by sonication or in 1% sodium dodecyl sulfate (SDS) with 2 mercaptoethanol and 8 M urea. The solubilized MB protein produced 3 peaks by Sephadex G 100 chromatography and at least five intense protein bands by SDS polyacrylamide gel electrophoresis. Serum sample and the fractions from control livers contained several protein bands which were similar to the major components of isolated MB protein. These morphological and biochemical findings suggest that MBs are not homogeneous protein, but they are probably complexes of various proteins and that some components of MBs are present in normal hepatocytes."}
{"id": "PMID:189566", "title": "Pancreatic carcinoma in infancy. An electron microscopic study.", "content": "A case of a malignant epithelial tumor of tail of the pancreas in a 3-year-old Japanese girl is presented. This is the fourth case reported with ultrastructural study. This type of pancreatic carcinoma of the infant has no endocrine granules or endocrine function. The ultrastructural study suggests that the tumor is derived from a primitive epithelial cell with differentiation toward acinar cell.", "contents": "Pancreatic carcinoma in infancy. An electron microscopic study. A case of a malignant epithelial tumor of tail of the pancreas in a 3-year-old Japanese girl is presented. This is the fourth case reported with ultrastructural study. This type of pancreatic carcinoma of the infant has no endocrine granules or endocrine function. The ultrastructural study suggests that the tumor is derived from a primitive epithelial cell with differentiation toward acinar cell."}
{"id": "PMID:189567", "title": "Methyldopa binding to cells in culture.", "content": "Cells from a rat hepatoma grown in culture were found to activate methyldopa to intermediates which are bound irreversibly to cellular proteins. The binding reaction was not inhibited by superoxide dismutase or allopurinol, but was strongly inhibited by ascorbic acid and glutathione. Methyldopa, paracetamol and furosemide were not mutagenic in the Salmonella/mammalian-microsome mutagenicity test.", "contents": "Methyldopa binding to cells in culture. Cells from a rat hepatoma grown in culture were found to activate methyldopa to intermediates which are bound irreversibly to cellular proteins. The binding reaction was not inhibited by superoxide dismutase or allopurinol, but was strongly inhibited by ascorbic acid and glutathione. Methyldopa, paracetamol and furosemide were not mutagenic in the Salmonella/mammalian-microsome mutagenicity test."}
{"id": "PMID:189568", "title": "Hydrosmotic effect of angiotensin II in the toad skin: role of cyclic AMP.", "content": "The mechanism of action of the hydrosmotic response of the isolated skin of the toad Bufo arenarum Hensel to angiotensin II was studied by means of an indirect pharmacological approach. Angiotensin II (2.10(-10) M), vasopressin (2.10(-13) M) and theophylline (10(-4) and 10(-3) M) in subliminal doses produced a significant increase on water permeability when added in different paired combinations. Angiotensin II (2.10(-7) M) and vasopressin (2.10(-8) M) in doses producing significant effects on water permeability increased the response to submaximal doses of epinephrine (10(-6) M) but not to higher doses (10(-5) M). Acid pH (6.4) and prostaglandin E1 (2.10(-7) M) reduced significantly the hydrosmotic response to angiotensin II, but in contrast with the toad bladder, the effect was not completely abolished. Present results support the view that the hydrosmotic effect of angiotensin II in toad skin is mediated by the adenylate cyclase - cyclic AMP system.", "contents": "Hydrosmotic effect of angiotensin II in the toad skin: role of cyclic AMP. The mechanism of action of the hydrosmotic response of the isolated skin of the toad Bufo arenarum Hensel to angiotensin II was studied by means of an indirect pharmacological approach. Angiotensin II (2.10(-10) M), vasopressin (2.10(-13) M) and theophylline (10(-4) and 10(-3) M) in subliminal doses produced a significant increase on water permeability when added in different paired combinations. Angiotensin II (2.10(-7) M) and vasopressin (2.10(-8) M) in doses producing significant effects on water permeability increased the response to submaximal doses of epinephrine (10(-6) M) but not to higher doses (10(-5) M). Acid pH (6.4) and prostaglandin E1 (2.10(-7) M) reduced significantly the hydrosmotic response to angiotensin II, but in contrast with the toad bladder, the effect was not completely abolished. Present results support the view that the hydrosmotic effect of angiotensin II in toad skin is mediated by the adenylate cyclase - cyclic AMP system."}
{"id": "PMID:189569", "title": "Comparative biosynthesis of polyethylenic fatty acids in Acanthamoeba castellanii and Ochromonas danica.", "content": "Acanthamoeba castellanii were incubated in vivo with 1(-14)C linoleic and 1(-14)C-alpha-linolenic acids. The incorporation of the acids into lipid fractions was studied. Labeling was found mainly in triglycerides and phospholipids. Homogenized cells and subcellular fractions separated by centrifugation were incubated with 1-14C-linoleic. 1-14C -alpha-linoleic and 1-14C eicosa-8,11-dienoic acids in the presence of NADH, ATP, and CoA. Different metabolic routes were demonstrated. omega3 and omega6 desaturases of the vegetal type, as well as a delta6 desaturation of alpha-linolenic acid of the animal type were present. The supernatant of 100000 x g contained both types of desaturating enzymes, whereas the corresponding particulated fraction was inactive. The ultrastructure of Acanthamoeba showed the endoplasmic reticulum with a poorly developed membrane component. The metabolic pathways found with Acanthamoeba were compared to Ochromonas danica incubated with linoleic acid in the light and in darkness. Desaturases typical of \"vegetal\" and \"animal\" pathways were found in both organisms. In both of them, alpha-linolenic and arachidonic acids could be synthetized. However, alpha-linolenic acid, typical of vegetal synthesis, was only stored in Ochromonas due to the presence of a photosynthetic machinery.", "contents": "Comparative biosynthesis of polyethylenic fatty acids in Acanthamoeba castellanii and Ochromonas danica. Acanthamoeba castellanii were incubated in vivo with 1(-14)C linoleic and 1(-14)C-alpha-linolenic acids. The incorporation of the acids into lipid fractions was studied. Labeling was found mainly in triglycerides and phospholipids. Homogenized cells and subcellular fractions separated by centrifugation were incubated with 1-14C-linoleic. 1-14C -alpha-linoleic and 1-14C eicosa-8,11-dienoic acids in the presence of NADH, ATP, and CoA. Different metabolic routes were demonstrated. omega3 and omega6 desaturases of the vegetal type, as well as a delta6 desaturation of alpha-linolenic acid of the animal type were present. The supernatant of 100000 x g contained both types of desaturating enzymes, whereas the corresponding particulated fraction was inactive. The ultrastructure of Acanthamoeba showed the endoplasmic reticulum with a poorly developed membrane component. The metabolic pathways found with Acanthamoeba were compared to Ochromonas danica incubated with linoleic acid in the light and in darkness. Desaturases typical of \"vegetal\" and \"animal\" pathways were found in both organisms. In both of them, alpha-linolenic and arachidonic acids could be synthetized. However, alpha-linolenic acid, typical of vegetal synthesis, was only stored in Ochromonas due to the presence of a photosynthetic machinery."}
{"id": "PMID:189570", "title": "On the mechanism of the depressor reaction upon afferent vagal stimulation in cats. II. Role of the beta-adrenergic structures for the development of the depressor reaction.", "content": "Electrical stimulation of the central section of the cervical vagus in cats with bilateral vagotomy results in lowering of the arterial blood pressure. A study is made of the effect of some beta-adrenotropic drugs on the depressor reaction. Propranolol (3 mg/kg i.v.) causes considerable blocking of the depressor reaction in all experiments. On the other hand, Isoprenaline ( a. 10 mug/kh/min) results in a considerable increase of this reaction. The administration of Propranolol (3 mg/kg) and Phentolamine (2 mg/kg) causes almost complete blocking of the reaction. A conclusion is made on the basis of these data that both alpha- and beta-adrenergic structures take part in the realization and development of the depressor reaction upon afferent vagal stimulation.", "contents": "On the mechanism of the depressor reaction upon afferent vagal stimulation in cats. II. Role of the beta-adrenergic structures for the development of the depressor reaction. Electrical stimulation of the central section of the cervical vagus in cats with bilateral vagotomy results in lowering of the arterial blood pressure. A study is made of the effect of some beta-adrenotropic drugs on the depressor reaction. Propranolol (3 mg/kg i.v.) causes considerable blocking of the depressor reaction in all experiments. On the other hand, Isoprenaline ( a. 10 mug/kh/min) results in a considerable increase of this reaction. The administration of Propranolol (3 mg/kg) and Phentolamine (2 mg/kg) causes almost complete blocking of the reaction. A conclusion is made on the basis of these data that both alpha- and beta-adrenergic structures take part in the realization and development of the depressor reaction upon afferent vagal stimulation."}
{"id": "PMID:189571", "title": "Structural model of vestibular effects on the blood pressure.", "content": "The model described in the present work is a structural presentation of certain aspcets of the vesibular effects on the blood pressure. The model comprises the joint action of the otolith system and the semicircular canals, gangl. Scarpe, the vestibular nuclei, the vasomotor centre and the nuclei of n. vagus. The direct transfer of information both from gangl. Scarpe to the vasoregulating centre and from nucl. Schwalbe to the vagal nuclei, as well as its polysynaptic transmission, are considered. The model examines a case when only two factors, namely decrease in the heart rate controlled by n. vagus and decrease in the heart tone controlled by the vasoregulating centre, determine the effect of blood pressure drop after vestibular stimulation. The structure of the model is flexible and permits its elaboration by including additional factors for the blood pressure drop.", "contents": "Structural model of vestibular effects on the blood pressure. The model described in the present work is a structural presentation of certain aspcets of the vesibular effects on the blood pressure. The model comprises the joint action of the otolith system and the semicircular canals, gangl. Scarpe, the vestibular nuclei, the vasomotor centre and the nuclei of n. vagus. The direct transfer of information both from gangl. Scarpe to the vasoregulating centre and from nucl. Schwalbe to the vagal nuclei, as well as its polysynaptic transmission, are considered. The model examines a case when only two factors, namely decrease in the heart rate controlled by n. vagus and decrease in the heart tone controlled by the vasoregulating centre, determine the effect of blood pressure drop after vestibular stimulation. The structure of the model is flexible and permits its elaboration by including additional factors for the blood pressure drop."}
{"id": "PMID:189572", "title": "EEG-studies on the phases of sleep and wakefulness after bilateral labyrinth destruction.", "content": "The dynamics of the state of wakefulness, slow and paradoxical sleep after labyrinth destruction was studied in chronic cats. The states were assessed according to the behaviour, EEG, myogram and eye movements. The labyrinth destruction was combined (chemical and mechanical). Bilateral labyrinth deafferentation results in a decrease in the duration of wakefulness from 30 to 17 per cent, p less than 0.001. At the same time paradoxical sleep increased from 4 to 8 per cent, p less than 0.001. This increase is due to both the greater average number of paradoxical sleep episodes and a higher average duration of the individual episode. The latency of the first appearance of a paradoxical sleep episode is considerably shortened after labyrinth destruction.", "contents": "EEG-studies on the phases of sleep and wakefulness after bilateral labyrinth destruction. The dynamics of the state of wakefulness, slow and paradoxical sleep after labyrinth destruction was studied in chronic cats. The states were assessed according to the behaviour, EEG, myogram and eye movements. The labyrinth destruction was combined (chemical and mechanical). Bilateral labyrinth deafferentation results in a decrease in the duration of wakefulness from 30 to 17 per cent, p less than 0.001. At the same time paradoxical sleep increased from 4 to 8 per cent, p less than 0.001. This increase is due to both the greater average number of paradoxical sleep episodes and a higher average duration of the individual episode. The latency of the first appearance of a paradoxical sleep episode is considerably shortened after labyrinth destruction."}
{"id": "PMID:189573", "title": "On certain relationships between gamma-aminobutyric acid (GABA) and adrenergic mechanisms in convulsive-seizure reaction.", "content": "In experiments on male albino mice it has been established that upon intracerebroventricular administration in doses of 50, 100 and 300 mug per mouse GABA markedly inhibits the convulsive-seizure reactions in pentylenetetrazol and electroconvulsions and has no substantial effect on strychnine convulsions (the dose of 300 mug is toxic). Diethyldithiocarbamate (DDC) in a dose of 400 mg/kg, introduced i.p. 3 hours in advance, increases the convulsive reactivity in pentylenetetrazol and electroconvulsions. On the background of DDC the inhibitory effect of GABA is expressed only in antagonizing of the DDC effect increasing the convulsive reactivity. Alpha-methyl-paratyrosine (a-MT) in a dose of 250 mg/kg, introduced i.p. 4 hours in advance, has no substantial effect on the convulsive reactivity. On the background of alpha-MT the inhibitory effect of GABA in electroconvulsions does not change essentially, however, in pentylenetetrazol convulsions the GABA effect is practically not manifested. The results obtained show that the changes in the correlations between the catecholamines and GABA in the central nervous system result in substantial changes in the convulsive-seizure reactivity. The lower catecholamines level does not permit the marked manifestation of the GABA inhibitory effect. However, GABA counteracts to a certain extent the rise in the convulsive reactivity as a result of the drop in the brain level of the catecholamines.", "contents": "On certain relationships between gamma-aminobutyric acid (GABA) and adrenergic mechanisms in convulsive-seizure reaction. In experiments on male albino mice it has been established that upon intracerebroventricular administration in doses of 50, 100 and 300 mug per mouse GABA markedly inhibits the convulsive-seizure reactions in pentylenetetrazol and electroconvulsions and has no substantial effect on strychnine convulsions (the dose of 300 mug is toxic). Diethyldithiocarbamate (DDC) in a dose of 400 mg/kg, introduced i.p. 3 hours in advance, increases the convulsive reactivity in pentylenetetrazol and electroconvulsions. On the background of DDC the inhibitory effect of GABA is expressed only in antagonizing of the DDC effect increasing the convulsive reactivity. Alpha-methyl-paratyrosine (a-MT) in a dose of 250 mg/kg, introduced i.p. 4 hours in advance, has no substantial effect on the convulsive reactivity. On the background of alpha-MT the inhibitory effect of GABA in electroconvulsions does not change essentially, however, in pentylenetetrazol convulsions the GABA effect is practically not manifested. The results obtained show that the changes in the correlations between the catecholamines and GABA in the central nervous system result in substantial changes in the convulsive-seizure reactivity. The lower catecholamines level does not permit the marked manifestation of the GABA inhibitory effect. However, GABA counteracts to a certain extent the rise in the convulsive reactivity as a result of the drop in the brain level of the catecholamines."}
{"id": "PMID:189576", "title": "Treatment of malignant metastatic pancreatic insulinoma with streptozotocin. Review of 21 cases described in detail in the literature and report of complete remission of a new case.", "content": "The possibilities of treating different types of pancreatic islet cell cancer with the active drug streptozotocin have been studied in reports of 21 patients published during the last 8 years. The unusual features of the symptomatology, dosage and injection methods, side-effects after different infusion schedules and complications of streptozotocin therapy, are compared. A new case with pancreatic carcinoma and liver metastases was treated with a total dose of 14 g streptozotocin, divided into 7 injections with an increasing interval between them. This patient underwent a marked amelioration of the disease, without serious side-effects of the streptozotocin treatment. She has been apparently well for the 22 months which have now elapsed since the beginning of treatment. This seems to be one of the longest remission periods yet published in the insulinoma literature.", "contents": "Treatment of malignant metastatic pancreatic insulinoma with streptozotocin. Review of 21 cases described in detail in the literature and report of complete remission of a new case. The possibilities of treating different types of pancreatic islet cell cancer with the active drug streptozotocin have been studied in reports of 21 patients published during the last 8 years. The unusual features of the symptomatology, dosage and injection methods, side-effects after different infusion schedules and complications of streptozotocin therapy, are compared. A new case with pancreatic carcinoma and liver metastases was treated with a total dose of 14 g streptozotocin, divided into 7 injections with an increasing interval between them. This patient underwent a marked amelioration of the disease, without serious side-effects of the streptozotocin treatment. She has been apparently well for the 22 months which have now elapsed since the beginning of treatment. This seems to be one of the longest remission periods yet published in the insulinoma literature."}
{"id": "PMID:189577", "title": "Serum lipid and lipoprotein concentrations in chronic uremia.", "content": "The concentrations of triglycerides and cholesterol have been determined in total serum and in the three major serum lipoprotein classes--very low (VLDL), low (LDL) and high (HDL) density lipoproteins-after an overnight fast in 39 patients with chronic uremia of more than 2 years' duration and with serum creatinine above 350 mumol/l. The values were compared with data from healthy male and female controls. The findings were similar for male and female uremics. Hypertriglyceridemia was common while serum cholesterol tended to be normal or subnormal. With the conventional typing system for hyperlipidemia, types II A, III and IV were present in 6,9 and 30%,respectively. The tryglyceride and cholesterol concentrations in VLDL were increased, while their normal relation for this lipoprotein class was maintained. In LDL the concentration of tryglycerides was increased, while that of cholesterol was low. The LDL composition, therefore, was changed to be more triglyceride-rich than normal. The changes in concentration and composition of LDL indicated that the levels of LDL 1 were raised and of LDL 2 decreased in chronic uremia. Increased levels of LDL tryglycerides occurred more frequently (40%) than increased levels of VLDL triglycerides (33%). The most striking and consistent lipoprotein abnormality was a low HDL cholesterol, which was not related to high VLDL levels. The HDL tryglycerides, on the other hand, tended to be somewhat high. The importance of the raised levels of the triglyceride-rich VLDL and LDL 1 and the decreased levels of HLD cholesterol for the rapid development of atherosclerotic vascular diseases which occur in chronic uremia is discussed. It is of interest in this context that both total cholesterol and LDL cholesterol were low. The possible mechanisms underlying the lipoprotein abnormalities in chronic uremia are discussed and it is suggested that they are complex.", "contents": "Serum lipid and lipoprotein concentrations in chronic uremia. The concentrations of triglycerides and cholesterol have been determined in total serum and in the three major serum lipoprotein classes--very low (VLDL), low (LDL) and high (HDL) density lipoproteins-after an overnight fast in 39 patients with chronic uremia of more than 2 years' duration and with serum creatinine above 350 mumol/l. The values were compared with data from healthy male and female controls. The findings were similar for male and female uremics. Hypertriglyceridemia was common while serum cholesterol tended to be normal or subnormal. With the conventional typing system for hyperlipidemia, types II A, III and IV were present in 6,9 and 30%,respectively. The tryglyceride and cholesterol concentrations in VLDL were increased, while their normal relation for this lipoprotein class was maintained. In LDL the concentration of tryglycerides was increased, while that of cholesterol was low. The LDL composition, therefore, was changed to be more triglyceride-rich than normal. The changes in concentration and composition of LDL indicated that the levels of LDL 1 were raised and of LDL 2 decreased in chronic uremia. Increased levels of LDL tryglycerides occurred more frequently (40%) than increased levels of VLDL triglycerides (33%). The most striking and consistent lipoprotein abnormality was a low HDL cholesterol, which was not related to high VLDL levels. The HDL tryglycerides, on the other hand, tended to be somewhat high. The importance of the raised levels of the triglyceride-rich VLDL and LDL 1 and the decreased levels of HLD cholesterol for the rapid development of atherosclerotic vascular diseases which occur in chronic uremia is discussed. It is of interest in this context that both total cholesterol and LDL cholesterol were low. The possible mechanisms underlying the lipoprotein abnormalities in chronic uremia are discussed and it is suggested that they are complex."}
{"id": "PMID:189578", "title": "Aldosterone response to ACTH stimulation in anephric and non-nephrectomized patients on regular hemodialysis.", "content": "The effect of ACTH on plasma aldosterone concentration (PAC) and plasma cortisol concentration (PCC) has been investigated in 5 anephric and 6 non-nephrectomized patients on regular homodialysis. Basal PAC was significantly lower (p less than 0.01) in the anephric (mean 37.6 pg/ml) than in the nonnephrectomized group (mean 117.5 pg/ml), whereas basal PCC (18.6 and 16.5 mug/100 ml, respectively) did not differ significantly (p less than 0.05). Following administration of synthetic beta1-24 ACTH, the maximal percentage increase in PAC was significantly lower ( less than 0.001) in the anephric (105%) than in the nonnephrectomized group (286%). The rise in PCC, 118%, in both groups showed no significant difference (p less than 0.05). The higher basal level of PAC and the more pronounced response to ACTH in nonnephrectomized patients correlated with higher basal levels of plasma renin activity compared with the anephric group. An influence of the remaining renin-angiotensin system on the ability to react to an ACTH stimulation is therefore suggested.", "contents": "Aldosterone response to ACTH stimulation in anephric and non-nephrectomized patients on regular hemodialysis. The effect of ACTH on plasma aldosterone concentration (PAC) and plasma cortisol concentration (PCC) has been investigated in 5 anephric and 6 non-nephrectomized patients on regular homodialysis. Basal PAC was significantly lower (p less than 0.01) in the anephric (mean 37.6 pg/ml) than in the nonnephrectomized group (mean 117.5 pg/ml), whereas basal PCC (18.6 and 16.5 mug/100 ml, respectively) did not differ significantly (p less than 0.05). Following administration of synthetic beta1-24 ACTH, the maximal percentage increase in PAC was significantly lower ( less than 0.001) in the anephric (105%) than in the nonnephrectomized group (286%). The rise in PCC, 118%, in both groups showed no significant difference (p less than 0.05). The higher basal level of PAC and the more pronounced response to ACTH in nonnephrectomized patients correlated with higher basal levels of plasma renin activity compared with the anephric group. An influence of the remaining renin-angiotensin system on the ability to react to an ACTH stimulation is therefore suggested."}
{"id": "PMID:189579", "title": "Simultaneous occurrence of right supratentorial meningioma and glioblastoma multiforme. Case report.", "content": "We report the case of a 63 years old male with two intracranial tumours, a meningioma and a glioblastoma multiforme. We have reviewed the relevant literature, and have speculated on the causes of this phenomenon.", "contents": "Simultaneous occurrence of right supratentorial meningioma and glioblastoma multiforme. Case report. We report the case of a 63 years old male with two intracranial tumours, a meningioma and a glioblastoma multiforme. We have reviewed the relevant literature, and have speculated on the causes of this phenomenon."}
{"id": "PMID:189582", "title": "Electrochemical neuron model.", "content": "1) A mathematical model for the behavior of passive iron in nitric acid, based on the electrochemical mechanisms, has been proposed. The model is capable of explaining several phenomena including threshold for activation, monostable property, periodic activation, propagation of activation, and threshold for propagation. Furthermore, the mathematical model predicts that the electrochemical active line has a specific propagated waveform and velocity of propagation. 2) By using iron-silver junctions in nitric acid, we could form a McCulloch-Pitts type neuron model. Also we could show the occurrence of reverberation on a net of iron wires in nitric acid.", "contents": "Electrochemical neuron model. 1) A mathematical model for the behavior of passive iron in nitric acid, based on the electrochemical mechanisms, has been proposed. The model is capable of explaining several phenomena including threshold for activation, monostable property, periodic activation, propagation of activation, and threshold for propagation. Furthermore, the mathematical model predicts that the electrochemical active line has a specific propagated waveform and velocity of propagation. 2) By using iron-silver junctions in nitric acid, we could form a McCulloch-Pitts type neuron model. Also we could show the occurrence of reverberation on a net of iron wires in nitric acid."}
{"id": "PMID:189591", "title": "Prolactin influences upon androgen action in male accessory sex organs.", "content": "The hormones of the pituitary gland are capable of directly influencing the function of male accessory sex organs. Among these hormones, prolactin in particular has been observed to enhance consistently the effects of androgens in the prostate gland and/or the seminal vesicles of rats, mice, and guinea pigs as well as in the accessory sex organs of other species. Prolactin-mediated augmentation of testosterone's effects upon these tissues is related primarily to the growth-promoting influences of this steroid. However, under certain experimental conditions, the androgen-dependent production of secretions by these organs has also been enhanced by prolactin treatment. Studies in the mouse have indicated that prolactin primarily enhances the proliferative phase of androgen action in male accessory sex tissues. Testosterone stimulation of RNA synthesis was unaffected by simultaneous administration of prolactin. The mechanism by which prolactin causes enhanced androgen responses in the prostate gland and seminal vesicles is not well understood. It would appear, however, that prolactin neither stimulates increased accumulation of androgen into the accessory sex organs, nor does it enhance the conversion of testosterone to the more \"active\" androgen, dihydrotestosterone. The effects of prolactin on these tissues are, however, dependent upon the presence of dihydrotestosterone. Uncertain, at present, are the possible effects of prolactin on the binding or retention of androgens (dihydrotestosterone?) in the prostate gland or in the seminal vesicles. There is evidence that hypophysectomy reduces the nuclear binding of dihydrotestosterone in the cells of the prostate gland. Perhaps prolactin is a pituitary factor(s) which is important in regulating nuclear binding of dihydrotestosterone in male accessory sex organs. The direct influences of prolactin upon androgen action in the cells of the accessory sex organs may involve several sites of action (Figure 2). For example, it is currently understood that when testosterone enters the cell cytoplasm it is subsequently converted to the more \"active\" androgen, dihydrotestosterone (DHT), by reduction at the 5alpha position. Dihydrotestosterone is then either bound to a cytoplasmic \"receptor\" protein (Rc) or is further metabolized to either 5alpha-androstane-3alpha,17beta-diol or 5alpha-androstane-3beta,17beta-diol (DIOL). The binding of DHT to its cytoplasmic receptor protein results in translocation of the steroid-receptor complex into the nucleus where presumably the complex dissociates and DHT exerts its androgenic effects. The transport of DHT to the nucleus can also result from the conversion of testosterone to DHT by nuclear membrane-bound 5alpha-reductase. Prolactin augmentation of DHT effects is envisioned as resulting from interaction of prolactin with its receptor, which due to the large size of the prolactin molecule is probably located in or on the plasma membrane...", "contents": "Prolactin influences upon androgen action in male accessory sex organs. The hormones of the pituitary gland are capable of directly influencing the function of male accessory sex organs. Among these hormones, prolactin in particular has been observed to enhance consistently the effects of androgens in the prostate gland and/or the seminal vesicles of rats, mice, and guinea pigs as well as in the accessory sex organs of other species. Prolactin-mediated augmentation of testosterone's effects upon these tissues is related primarily to the growth-promoting influences of this steroid. However, under certain experimental conditions, the androgen-dependent production of secretions by these organs has also been enhanced by prolactin treatment. Studies in the mouse have indicated that prolactin primarily enhances the proliferative phase of androgen action in male accessory sex tissues. Testosterone stimulation of RNA synthesis was unaffected by simultaneous administration of prolactin. The mechanism by which prolactin causes enhanced androgen responses in the prostate gland and seminal vesicles is not well understood. It would appear, however, that prolactin neither stimulates increased accumulation of androgen into the accessory sex organs, nor does it enhance the conversion of testosterone to the more \"active\" androgen, dihydrotestosterone. The effects of prolactin on these tissues are, however, dependent upon the presence of dihydrotestosterone. Uncertain, at present, are the possible effects of prolactin on the binding or retention of androgens (dihydrotestosterone?) in the prostate gland or in the seminal vesicles. There is evidence that hypophysectomy reduces the nuclear binding of dihydrotestosterone in the cells of the prostate gland. Perhaps prolactin is a pituitary factor(s) which is important in regulating nuclear binding of dihydrotestosterone in male accessory sex organs. The direct influences of prolactin upon androgen action in the cells of the accessory sex organs may involve several sites of action (Figure 2). For example, it is currently understood that when testosterone enters the cell cytoplasm it is subsequently converted to the more \"active\" androgen, dihydrotestosterone (DHT), by reduction at the 5alpha position. Dihydrotestosterone is then either bound to a cytoplasmic \"receptor\" protein (Rc) or is further metabolized to either 5alpha-androstane-3alpha,17beta-diol or 5alpha-androstane-3beta,17beta-diol (DIOL). The binding of DHT to its cytoplasmic receptor protein results in translocation of the steroid-receptor complex into the nucleus where presumably the complex dissociates and DHT exerts its androgenic effects. The transport of DHT to the nucleus can also result from the conversion of testosterone to DHT by nuclear membrane-bound 5alpha-reductase. Prolactin augmentation of DHT effects is envisioned as resulting from interaction of prolactin with its receptor, which due to the large size of the prolactin molecule is probably located in or on the plasma membrane..."}
{"id": "PMID:189596", "title": "Neonatal hypoglycemia resulting from islet cell adenomatosis. Successful treatment with total pancreatectomy.", "content": "A female infant developed apneic spells due to hypoglycemia at 73 hours of life. It was impossible to maintain the blood glucose level despite continuous intravenously given dextrose, cortisone, diazoxide, and a low-leucine diet. A subtotal pancreatectomy was performed but there was no evidence of islet cell adenoma. On second laparotomy, the head of the pancreas was removed, and on microscopic examination, islet cell adenomatosis was found. A good clinical recovery followed. Follow-up at age 3 years and 4 months shows apparently normal mental and physical development.", "contents": "Neonatal hypoglycemia resulting from islet cell adenomatosis. Successful treatment with total pancreatectomy. A female infant developed apneic spells due to hypoglycemia at 73 hours of life. It was impossible to maintain the blood glucose level despite continuous intravenously given dextrose, cortisone, diazoxide, and a low-leucine diet. A subtotal pancreatectomy was performed but there was no evidence of islet cell adenoma. On second laparotomy, the head of the pancreas was removed, and on microscopic examination, islet cell adenomatosis was found. A good clinical recovery followed. Follow-up at age 3 years and 4 months shows apparently normal mental and physical development."}
{"id": "PMID:189598", "title": "Histamine, cyclic AMP, and gastric secretion in the dog.", "content": "Canine gastric mucosal cyclic AMP content was determined at 1, 5, 30, 60, and 120 min after commencing a 2-hr continuous intravenous infusion of histamine of sufficient dose to elicit a brisk acid secretory response from the dog stomach. The increase in acid output was significant at 30 min and stabilized at the stimulated level for the duration of histamine infusion. By contrast, there was no significant increase in mucosal cyclic AMP content at any time of measurement. Our findings indicate that the acid secretory response of the canine stomach to histamine does not require prior accumulation of cyclic AMP in the mucosal tissue.", "contents": "Histamine, cyclic AMP, and gastric secretion in the dog. Canine gastric mucosal cyclic AMP content was determined at 1, 5, 30, 60, and 120 min after commencing a 2-hr continuous intravenous infusion of histamine of sufficient dose to elicit a brisk acid secretory response from the dog stomach. The increase in acid output was significant at 30 min and stabilized at the stimulated level for the duration of histamine infusion. By contrast, there was no significant increase in mucosal cyclic AMP content at any time of measurement. Our findings indicate that the acid secretory response of the canine stomach to histamine does not require prior accumulation of cyclic AMP in the mucosal tissue."}
{"id": "PMID:189599", "title": "Simultaneous infection with type A and B hepatitis viruses.", "content": "The occurrence of a common source hepatitis A epidemic among the residents of a New England state mental institution where hepatitis B is hyperendemic provided an opportunity to observe concurrent infections with both agents. Nine HBsAg-positive individuals developed hepatitis A infections documented by hepatitis A antibody seroconversion in eight. The incidence of hepatitis A infections in susceptible HBsAg-positive persons (67%) did not differ from that in HBsAg-negative individuals (63%). The icteric to anicteric infection ratio in the HBsAG-positives (1:1.7) was similar to that in the negatives (1:2.1), and the clinical course in the antigen positives did not differ significantly from that of the antigen negatives. In addition to confirming previous reports that the viruses of hepatitis A and B are immunologically distinct, these results document that infection with either is independent of the other, and that the morbidity from simultaneous infection is no greater than that caused by either alone.", "contents": "Simultaneous infection with type A and B hepatitis viruses. The occurrence of a common source hepatitis A epidemic among the residents of a New England state mental institution where hepatitis B is hyperendemic provided an opportunity to observe concurrent infections with both agents. Nine HBsAg-positive individuals developed hepatitis A infections documented by hepatitis A antibody seroconversion in eight. The incidence of hepatitis A infections in susceptible HBsAg-positive persons (67%) did not differ from that in HBsAg-negative individuals (63%). The icteric to anicteric infection ratio in the HBsAG-positives (1:1.7) was similar to that in the negatives (1:2.1), and the clinical course in the antigen positives did not differ significantly from that of the antigen negatives. In addition to confirming previous reports that the viruses of hepatitis A and B are immunologically distinct, these results document that infection with either is independent of the other, and that the morbidity from simultaneous infection is no greater than that caused by either alone."}
{"id": "PMID:189600", "title": "Hepatitis Ain Greenland: importance of specific antibody testing in epidemiologic surveillance.", "content": "An epidemic of viral hepatitis type A in an arctic area is described. From 1970-1974, 4961 clinical cases of hepatitis were reported in Greenland, corresponding to 11 per cent of the total population. Epidemiologic surveillance indicated person-to-person transmission of the disease, apparently by the oralfecal route. The course of the disease was mild, and complications were rare with a case fatality rate of 0.3%. Ninety-three per cent of the cases occurred in individuals 1-25 years of age, suggesting widespread immunity in the adult population presumably due to infection with hepatitis A during a similar epidemic in 1947-1948. The occurrence of antibody to hepatitis A antigen (anti-HA) in healthy Greenlanders, as detected by radioimmunoassay, closely paralleled this observation. Anti-HA was present in 38 (93%) of 41 individuals born before 1948 and in one (3%) of 29 younger persons. Anti-HA also was detected during the epidemic in the sera of 25 randomly selected hepatitis cases. Immunoglobin analysis in three acute-phase sera showed anti-HA reactivity predominantly in the IgM fraction. The epidemic showed no relation to the hepatitis episodes occurring annually in the area, and seroepidemiologic data indicated that the endemic hepatitis may be caused by hepatitis B virus only.", "contents": "Hepatitis Ain Greenland: importance of specific antibody testing in epidemiologic surveillance. An epidemic of viral hepatitis type A in an arctic area is described. From 1970-1974, 4961 clinical cases of hepatitis were reported in Greenland, corresponding to 11 per cent of the total population. Epidemiologic surveillance indicated person-to-person transmission of the disease, apparently by the oralfecal route. The course of the disease was mild, and complications were rare with a case fatality rate of 0.3%. Ninety-three per cent of the cases occurred in individuals 1-25 years of age, suggesting widespread immunity in the adult population presumably due to infection with hepatitis A during a similar epidemic in 1947-1948. The occurrence of antibody to hepatitis A antigen (anti-HA) in healthy Greenlanders, as detected by radioimmunoassay, closely paralleled this observation. Anti-HA was present in 38 (93%) of 41 individuals born before 1948 and in one (3%) of 29 younger persons. Anti-HA also was detected during the epidemic in the sera of 25 randomly selected hepatitis cases. Immunoglobin analysis in three acute-phase sera showed anti-HA reactivity predominantly in the IgM fraction. The epidemic showed no relation to the hepatitis episodes occurring annually in the area, and seroepidemiologic data indicated that the endemic hepatitis may be caused by hepatitis B virus only."}
{"id": "PMID:189601", "title": "An outbreak of type A viral hepatitis at the Naval Training Center, San Diego: epidemiologic evaluation.", "content": "In October 1974, a large foodborne outbreak of hepatitis occurred among naval personnel undergoing basic training at the Naval Training Center, San Diego, California. Of the 2781 recruits eating at the implicated dining hall on the day disease transmission occurred, 133 developed clinical or laboratory evidence of hepatitis for an attack rate of 47.8/1000. The epidemiologic investigation suggested that hepatitis A virus was the etiologic agent, and this was subsequently confirmed by laboratory examination. The index and source case was a recuit food-handler who experienced prodromal symptoms of hepatitis while preparing salads and fresh fruit 32 days prior to the outbreak. A food preference questionnaire implicated tossed salad and fresh grapefruit as the specific vehicles of transmission.", "contents": "An outbreak of type A viral hepatitis at the Naval Training Center, San Diego: epidemiologic evaluation. In October 1974, a large foodborne outbreak of hepatitis occurred among naval personnel undergoing basic training at the Naval Training Center, San Diego, California. Of the 2781 recruits eating at the implicated dining hall on the day disease transmission occurred, 133 developed clinical or laboratory evidence of hepatitis for an attack rate of 47.8/1000. The epidemiologic investigation suggested that hepatitis A virus was the etiologic agent, and this was subsequently confirmed by laboratory examination. The index and source case was a recuit food-handler who experienced prodromal symptoms of hepatitis while preparing salads and fresh fruit 32 days prior to the outbreak. A food preference questionnaire implicated tossed salad and fresh grapefruit as the specific vehicles of transmission."}
{"id": "PMID:189604", "title": "Herpes zoster and impaired cell-associated immunity to the varicella-zoster virus in patients with Hodgkin's disease.", "content": "Thirty-two patients with Hodgkin's disease and 12 normal donors were studied for their in vitro lymphocyte responsiveness to a membrane-associated varicella-zoster (VZ) antigen. When compared to the normal donors, patients with Hodgkin's disease in whom radiotherapy was recently completed and those with active, recurrent disease had markedly impaired cell-associated immunity to VZ antigen. In addition, there was a suggestion that patients in long-term remission who had received primary combined modality therapy (radiotherapy plus chemotherapy) had an impaired response when compared to normal persons or to patients who had received single modality therapy. Newly diagnosed, untreated patients with Hodgkin's disease did not differ significantly from normal persons as a group but two of six were unresponsive to the VZ antigen whereas all normal subjects were responsive. Most patients in remission for at least one year following therapy had normal in vitro responsiveness. In two patients herpes zoster developed after the demonstration of absent in vitro lymphocyte reactivity to the VZ antigen.", "contents": "Herpes zoster and impaired cell-associated immunity to the varicella-zoster virus in patients with Hodgkin's disease. Thirty-two patients with Hodgkin's disease and 12 normal donors were studied for their in vitro lymphocyte responsiveness to a membrane-associated varicella-zoster (VZ) antigen. When compared to the normal donors, patients with Hodgkin's disease in whom radiotherapy was recently completed and those with active, recurrent disease had markedly impaired cell-associated immunity to VZ antigen. In addition, there was a suggestion that patients in long-term remission who had received primary combined modality therapy (radiotherapy plus chemotherapy) had an impaired response when compared to normal persons or to patients who had received single modality therapy. Newly diagnosed, untreated patients with Hodgkin's disease did not differ significantly from normal persons as a group but two of six were unresponsive to the VZ antigen whereas all normal subjects were responsive. Most patients in remission for at least one year following therapy had normal in vitro responsiveness. In two patients herpes zoster developed after the demonstration of absent in vitro lymphocyte reactivity to the VZ antigen."}
{"id": "PMID:189605", "title": "Ectopic production of antidiuretic hormone (adh), adrenocorticotrophic hormone (ACTH) and beta-melanocyte stimulating hormone (beta-MSH) by an oat cell carcinoma of the lung.", "content": "A 61 year old woman presented with profound hyponatremia and markedly low serum osmolality. Urine osmolality was greater than the serum osmolality, an abnormality that was corrected by water restriction, suggesting inappropriate ADH secretion. Although there were no physical signs of Cushing's syndrome, her serum potassium level was low and markedly elevated levels of plasma and urine corticosteroids were not altered by the administration of large amounts of dexamethasone, suggesting the ectopic ACTH-MSH syndrome. Plasma levels of immunoreactive ACTH and beta-MSH were elevated. At autopsy, a metastastic oat cell carcinoma of the lung, not detected antemortem by chest roentgenograms and bronchoscopy, was found. Immunoreactive ADH, ACTH and beta-MSH were detected in the primary tumor and in metastases to the liver. beta-MSH was also detected in the spleen, in which metastases were observed. This is the first documented case of the simultaneous production of ADH, ACTH and beta-MSH by neoplastic tissue associated with clinical manifestations of the syndrome of inappropriate ADH secretion and the ectopic ACTH-MSH syndrome.", "contents": "Ectopic production of antidiuretic hormone (adh), adrenocorticotrophic hormone (ACTH) and beta-melanocyte stimulating hormone (beta-MSH) by an oat cell carcinoma of the lung. A 61 year old woman presented with profound hyponatremia and markedly low serum osmolality. Urine osmolality was greater than the serum osmolality, an abnormality that was corrected by water restriction, suggesting inappropriate ADH secretion. Although there were no physical signs of Cushing's syndrome, her serum potassium level was low and markedly elevated levels of plasma and urine corticosteroids were not altered by the administration of large amounts of dexamethasone, suggesting the ectopic ACTH-MSH syndrome. Plasma levels of immunoreactive ACTH and beta-MSH were elevated. At autopsy, a metastastic oat cell carcinoma of the lung, not detected antemortem by chest roentgenograms and bronchoscopy, was found. Immunoreactive ADH, ACTH and beta-MSH were detected in the primary tumor and in metastases to the liver. beta-MSH was also detected in the spleen, in which metastases were observed. This is the first documented case of the simultaneous production of ADH, ACTH and beta-MSH by neoplastic tissue associated with clinical manifestations of the syndrome of inappropriate ADH secretion and the ectopic ACTH-MSH syndrome."}
{"id": "PMID:189611", "title": "Ovarian extraembryonal teratoma. II. Endodermal sinus tumor mixed with other germ cell tumors.", "content": "From the files of the Emil Novak Ovarian Tumor Registry, 18 cases of mixed ovarian germ-cell neoplasms containing endodermal sinus tumor as one element have been reviewed. The data regarding the patient age, presenting symptoms, gross appearance of the tumors, and response to therapy are similar to those reported in a previous series of pure endodermal sinus tumors. Response to all modes of therapy is disappointing but there is growing evidence that combination chemotherapy should be added to surgical excision as a routine part of therapy in such patients. The rarity of this lesion is such that meaningful data are likely to be available only if individual and institutional experiences are combined in central tumor registries.", "contents": "Ovarian extraembryonal teratoma. II. Endodermal sinus tumor mixed with other germ cell tumors. From the files of the Emil Novak Ovarian Tumor Registry, 18 cases of mixed ovarian germ-cell neoplasms containing endodermal sinus tumor as one element have been reviewed. The data regarding the patient age, presenting symptoms, gross appearance of the tumors, and response to therapy are similar to those reported in a previous series of pure endodermal sinus tumors. Response to all modes of therapy is disappointing but there is growing evidence that combination chemotherapy should be added to surgical excision as a routine part of therapy in such patients. The rarity of this lesion is such that meaningful data are likely to be available only if individual and institutional experiences are combined in central tumor registries."}
{"id": "PMID:189607", "title": "Peripheral neuropathy caused by methaqualone.", "content": "Three patients are described who each received methaqualone and developed signs and symptoms of peripheral neuropathy. The subsequent improvement after cessation of methaqualone was highly suggestive or a direct toxic action of the drug or one of its metabolites. In one patient methaqualone was recommended with reappearance of signs and symptoms of peripheral neuropathy. Again cessation of the drug caused disappearance of these signs. There was no evidence whatsoever of any electrolyte or metabolic disturbance or any other pathology which might have given rise to this symptom complex. In addition, no other drugs were prescribed besides methaqualone.", "contents": "Peripheral neuropathy caused by methaqualone. Three patients are described who each received methaqualone and developed signs and symptoms of peripheral neuropathy. The subsequent improvement after cessation of methaqualone was highly suggestive or a direct toxic action of the drug or one of its metabolites. In one patient methaqualone was recommended with reappearance of signs and symptoms of peripheral neuropathy. Again cessation of the drug caused disappearance of these signs. There was no evidence whatsoever of any electrolyte or metabolic disturbance or any other pathology which might have given rise to this symptom complex. In addition, no other drugs were prescribed besides methaqualone."}
{"id": "PMID:189612", "title": "Circulatory response to systemic infusion of norepinephrine in the pregnant ewe.", "content": "Seven pregnant ewes from 100 to 137 days of gestation were infused with systemic doses of norepinephrine and uterine arterial flow dose-response curves were determined. A constant infusion of norepinephrine at a mean rate of 0.24 mug per minute per kilogram led to a 39.3 per cent decrease in total uterine arterial blood flow as measured with isotope-labeled microspheres while systemic pressure was unaltered. At this dose the reduction in endometrial blood flow (--64 per cent) was significantly greater than that in either the myometrium (--45 per cent) or placental cotyledons (--31 per cent) (p less than 0.005). Significant decreases in blood flow to small bowel, skeletal muscle, vagina, cervix. Fallopian tubes, kidneys, spleen, pancreas, and mammary gland were documented. There were no significant increases in blood flow. This study demonstrates that during the period or pregnancy studied, the overwhelming response to norepinephrine is vasoconstriction and that the vascular beds of all the tissues of pregnant uterus are sensitive to the alpha-adrenergic effects of norepinephrine.", "contents": "Circulatory response to systemic infusion of norepinephrine in the pregnant ewe. Seven pregnant ewes from 100 to 137 days of gestation were infused with systemic doses of norepinephrine and uterine arterial flow dose-response curves were determined. A constant infusion of norepinephrine at a mean rate of 0.24 mug per minute per kilogram led to a 39.3 per cent decrease in total uterine arterial blood flow as measured with isotope-labeled microspheres while systemic pressure was unaltered. At this dose the reduction in endometrial blood flow (--64 per cent) was significantly greater than that in either the myometrium (--45 per cent) or placental cotyledons (--31 per cent) (p less than 0.005). Significant decreases in blood flow to small bowel, skeletal muscle, vagina, cervix. Fallopian tubes, kidneys, spleen, pancreas, and mammary gland were documented. There were no significant increases in blood flow. This study demonstrates that during the period or pregnancy studied, the overwhelming response to norepinephrine is vasoconstriction and that the vascular beds of all the tissues of pregnant uterus are sensitive to the alpha-adrenergic effects of norepinephrine."}
{"id": "PMID:189613", "title": "Role of endogenous prostaglandins in regulation of uterine blood flow and adrenergic neurotransmission.", "content": "Earlier studies from these laboratories have demonstrated that prostaglandins (PG's) of the A and E series are potent uterine vasodilators whereas PGF's do not significantly alter uterine vascular resistance. In addition, PGE's and PGF's are also able to modify adrenergic vasoconstrictor responses in the canine uterus. In the present study the role of endogenous prostaglandins in regulating uterine vascular resistance and adrenergic neurotransmission was evaluated. Intra-arterial infusion of the prostaglandin synthesis inhibitor meclofenamate resulted in a significant reduction in PGE levels in uterine venous plasma and increased vascular resistance. Uterine vasoconstrictor responses produced by sympathetic nerve stimulation and norepinephrine were enhanced when endogenous PG synthesis was inhibited. During sympathetic nerve stimulation, uterine venous plasma levels of radioimmunoassayable prostaglandins of the E of F series did not change, suggesting that the adrenergic activation of PG synthesis is not detectable in uterine venous efferent. These data suggest that endogenous prostaglandins of the E series appear to play an important role in regulating uterine blood flow (I) by relaxing uterine vascular smooth muscle and (2) by depressing adrenergic vasoconstrictor responses.", "contents": "Role of endogenous prostaglandins in regulation of uterine blood flow and adrenergic neurotransmission. Earlier studies from these laboratories have demonstrated that prostaglandins (PG's) of the A and E series are potent uterine vasodilators whereas PGF's do not significantly alter uterine vascular resistance. In addition, PGE's and PGF's are also able to modify adrenergic vasoconstrictor responses in the canine uterus. In the present study the role of endogenous prostaglandins in regulating uterine vascular resistance and adrenergic neurotransmission was evaluated. Intra-arterial infusion of the prostaglandin synthesis inhibitor meclofenamate resulted in a significant reduction in PGE levels in uterine venous plasma and increased vascular resistance. Uterine vasoconstrictor responses produced by sympathetic nerve stimulation and norepinephrine were enhanced when endogenous PG synthesis was inhibited. During sympathetic nerve stimulation, uterine venous plasma levels of radioimmunoassayable prostaglandins of the E of F series did not change, suggesting that the adrenergic activation of PG synthesis is not detectable in uterine venous efferent. These data suggest that endogenous prostaglandins of the E series appear to play an important role in regulating uterine blood flow (I) by relaxing uterine vascular smooth muscle and (2) by depressing adrenergic vasoconstrictor responses."}
{"id": "PMID:189614", "title": "An evaluation of silicophosphate as an orthodontic cement.", "content": "In a laboratory and clinical evluation, when used for the cementation of orthodontic bands, a zinc silicophosphate cement has proved to be comparable to zinc phosphate cement in its bond strength to enamel. This was demonstrated in laboratory tests by higher values being required to break the mechanical bond and in the clinical study by the slightly smaller percentage of bands which became loose during orthodontic treatment. In both the laboratory and clinical studies it was found that silicophosphate remained attached to the enamel in higher percentages after a band had become loose. It also was found that the remaining cement was often quite difficult to remove from the enamel. Probably the greatest advantage of using silicophosphate is that no decalcification of enamel was found under bands which had become loose during orthodontic treatment. This may be attributable to the higher bond strength and/or the presence of fluoride in the cement. Further clinical studies of this nature appear warranted.", "contents": "An evaluation of silicophosphate as an orthodontic cement. In a laboratory and clinical evluation, when used for the cementation of orthodontic bands, a zinc silicophosphate cement has proved to be comparable to zinc phosphate cement in its bond strength to enamel. This was demonstrated in laboratory tests by higher values being required to break the mechanical bond and in the clinical study by the slightly smaller percentage of bands which became loose during orthodontic treatment. In both the laboratory and clinical studies it was found that silicophosphate remained attached to the enamel in higher percentages after a band had become loose. It also was found that the remaining cement was often quite difficult to remove from the enamel. Probably the greatest advantage of using silicophosphate is that no decalcification of enamel was found under bands which had become loose during orthodontic treatment. This may be attributable to the higher bond strength and/or the presence of fluoride in the cement. Further clinical studies of this nature appear warranted."}
{"id": "PMID:189615", "title": "Murine Type C viral envelope glycoprotein gp69/71 and lupus-like glomerulonephritis of New Zealand mice. An immunoperoxidase study.", "content": "The location of murine Type C viral envelope glycoprotein antigen in the glomerulonephritic kidneys of NZB and NZB/NZW F1 hybrid mice was analyzed by the indirect immunoperoxidase technique at light and electron microscopic levels. Immune complex deposits of the glycoprotein antigen were present in the glomeruli in mesangial and subepithelial sites. In addition to the glomerular depositions, viral envelope antigen was also present at the brush border of proximal tubular epithelial cells and in lymphoid cells infiltrating the kidneys of these mice.", "contents": "Murine Type C viral envelope glycoprotein gp69/71 and lupus-like glomerulonephritis of New Zealand mice. An immunoperoxidase study. The location of murine Type C viral envelope glycoprotein antigen in the glomerulonephritic kidneys of NZB and NZB/NZW F1 hybrid mice was analyzed by the indirect immunoperoxidase technique at light and electron microscopic levels. Immune complex deposits of the glycoprotein antigen were present in the glomeruli in mesangial and subepithelial sites. In addition to the glomerular depositions, viral envelope antigen was also present at the brush border of proximal tubular epithelial cells and in lymphoid cells infiltrating the kidneys of these mice."}
{"id": "PMID:189616", "title": "Virus-induced animal model of osteosarcoma in the rat: Morphologic and biochemical studies.", "content": "Osteosarcomas were produced by the intratibial inoculation of New Zealand black rats with Moloney sarcoma virus (MSV) at 1 day and 4 days of age. Radiographic evidence of osteosarcoma development was first demonstrated at 10 to 15 days postinoculation in both groups. Subsequent radiographic and light and electron microscopic evaluation of tumor-bearing rats demonstrated that osteosarcomas in rats inoculated at Day 4 of age were more osteoproliferative osteosarcomas than those in rats inoculated on Day 1. Rats inoculated at 4 days of age lived longer, had more slowly growing osteosarcomas, and developed a consistent tumor-associated cachexia compared to tumor-bearing rats inoculated at Day 1. Both groups of rats had a 93% metastasis rate involving either sublumbar lymph nodes, lungs, or both. Tumor-bearing rats inoculated at 4 days of age had consistent elevations in both urinary hydroxyproline excretion (HOP/CR) and serum alkaline phosphatase levels, and in serum calcium levels at some time points. The high tumor incidence after a short latent period and the morphologic and biochemical similarities between the MSV-induced murine osteosarcoma and the osteosarcoma in human beings makes this discrete tumor and a valuable animal model for the evaluation of new therapeutic regimens.", "contents": "Virus-induced animal model of osteosarcoma in the rat: Morphologic and biochemical studies. Osteosarcomas were produced by the intratibial inoculation of New Zealand black rats with Moloney sarcoma virus (MSV) at 1 day and 4 days of age. Radiographic evidence of osteosarcoma development was first demonstrated at 10 to 15 days postinoculation in both groups. Subsequent radiographic and light and electron microscopic evaluation of tumor-bearing rats demonstrated that osteosarcomas in rats inoculated at Day 4 of age were more osteoproliferative osteosarcomas than those in rats inoculated on Day 1. Rats inoculated at 4 days of age lived longer, had more slowly growing osteosarcomas, and developed a consistent tumor-associated cachexia compared to tumor-bearing rats inoculated at Day 1. Both groups of rats had a 93% metastasis rate involving either sublumbar lymph nodes, lungs, or both. Tumor-bearing rats inoculated at 4 days of age had consistent elevations in both urinary hydroxyproline excretion (HOP/CR) and serum alkaline phosphatase levels, and in serum calcium levels at some time points. The high tumor incidence after a short latent period and the morphologic and biochemical similarities between the MSV-induced murine osteosarcoma and the osteosarcoma in human beings makes this discrete tumor and a valuable animal model for the evaluation of new therapeutic regimens."}
{"id": "PMID:189617", "title": "Differential analyses of EMG findings in motor neuron lesions.", "content": "The principle in electromyography that positive sharp waves (PSW) and fibrillation potentials (FP) are pathognomonic of lower motor neuron (LMN) pathology is challenged by recent reports that the same potentials are observed in upper motor neuron (UMN) lesions. We have also observed positive sharp waves and fibrillation potentials in patients with UMN lesions, without conditions that involve the LMN. This study was undertaken to ascertain if there are differences in the potentials between the LMN and  UMN lesions. Twenty-five UMN and 25 LMN patients were electromyographed. Manual and computer analyses were used to compare parameters from positive sharp wave and fibrillation potentials. Our findings indicate that there are interlesion differences in the mean frequency of occurrence ratio of PSW to FP and in some of the durational wave parameters.", "contents": "Differential analyses of EMG findings in motor neuron lesions. The principle in electromyography that positive sharp waves (PSW) and fibrillation potentials (FP) are pathognomonic of lower motor neuron (LMN) pathology is challenged by recent reports that the same potentials are observed in upper motor neuron (UMN) lesions. We have also observed positive sharp waves and fibrillation potentials in patients with UMN lesions, without conditions that involve the LMN. This study was undertaken to ascertain if there are differences in the potentials between the LMN and  UMN lesions. Twenty-five UMN and 25 LMN patients were electromyographed. Manual and computer analyses were used to compare parameters from positive sharp wave and fibrillation potentials. Our findings indicate that there are interlesion differences in the mean frequency of occurrence ratio of PSW to FP and in some of the durational wave parameters."}
{"id": "PMID:189618", "title": "Control of intracellular Ca2+ activity in rat myometrium.", "content": "Four fractions enriched, respectively, in plasma membrane (PM), smooth endoplasmic reticulum (SER), rough endoplasmic reticulum (RER), and mitochondria were isolated from estrogen-dominated rat myometrium. Ca2+ uptake by these fractions was studied in order to estimate the relative potential of the corresponding organelles for controlling intracellular Ca2+ activity. Ca2+ uptake properties of the PM, SER, and RER fractions were similar except that potentiation by oxalate was in the order RER greater than or equal SER greater than PM. However, studies with the ionophores X-537A and A23187 suggested that Ca2+ was transported into the lumen of membrane vesicles of all these fractions. Unlike that of skeletal muscle sarcoplasmic reticulum, Ca2+ uptake by the myometrial fractions was not supported by high-energy compounds other than ATP. Mitochondria took up much less Ca2+ at low, and much more Ca2+ at high, free Ca2+ concentrations than did the other fractions. The amount of Ca2+ taken up in 30 s from a 1 muM free Ca2+ solution in the presence of ATP was similar for all fractions. These results suggested that mitochondria may act as an important Ca2+ control system in rat myometrium when the intracellular Ca2+ concentration is near 1 muM or higher, whereas the PM, SER, and RER may be of major importance at Ca2+ levels of 0.3 muM or lower.", "contents": "Control of intracellular Ca2+ activity in rat myometrium. Four fractions enriched, respectively, in plasma membrane (PM), smooth endoplasmic reticulum (SER), rough endoplasmic reticulum (RER), and mitochondria were isolated from estrogen-dominated rat myometrium. Ca2+ uptake by these fractions was studied in order to estimate the relative potential of the corresponding organelles for controlling intracellular Ca2+ activity. Ca2+ uptake properties of the PM, SER, and RER fractions were similar except that potentiation by oxalate was in the order RER greater than or equal SER greater than PM. However, studies with the ionophores X-537A and A23187 suggested that Ca2+ was transported into the lumen of membrane vesicles of all these fractions. Unlike that of skeletal muscle sarcoplasmic reticulum, Ca2+ uptake by the myometrial fractions was not supported by high-energy compounds other than ATP. Mitochondria took up much less Ca2+ at low, and much more Ca2+ at high, free Ca2+ concentrations than did the other fractions. The amount of Ca2+ taken up in 30 s from a 1 muM free Ca2+ solution in the presence of ATP was similar for all fractions. These results suggested that mitochondria may act as an important Ca2+ control system in rat myometrium when the intracellular Ca2+ concentration is near 1 muM or higher, whereas the PM, SER, and RER may be of major importance at Ca2+ levels of 0.3 muM or lower."}
{"id": "PMID:189619", "title": "Afferent discharges from venous pressoreceptors in liver.", "content": "Afterent discharges were observed in dissected filaments or single nerve fibers of hepatic nerve in the guinea pig and the rabbit. Increasing the perfusion pressure of the portal vein in isolated liver preparation in the guinea pig caused an increase in afferent discharge rate. Discharge patterns were compatible with those of the slowly adapting type. Increasing the portal venous pressure by means of intravenous injection of Locke's solution into the left jugular vein in the rabbit in vivo caused an increase in afferent discharge rate. Increasing the hepatic arterial pressure was without effect. It is suggested that pressoreceptors are present in or near the venous wall of the portal venous system and that they send information about blood pressure in the portal vein to the central nervous system.", "contents": "Afferent discharges from venous pressoreceptors in liver. Afterent discharges were observed in dissected filaments or single nerve fibers of hepatic nerve in the guinea pig and the rabbit. Increasing the perfusion pressure of the portal vein in isolated liver preparation in the guinea pig caused an increase in afferent discharge rate. Discharge patterns were compatible with those of the slowly adapting type. Increasing the portal venous pressure by means of intravenous injection of Locke's solution into the left jugular vein in the rabbit in vivo caused an increase in afferent discharge rate. Increasing the hepatic arterial pressure was without effect. It is suggested that pressoreceptors are present in or near the venous wall of the portal venous system and that they send information about blood pressure in the portal vein to the central nervous system."}
{"id": "PMID:189620", "title": "Regulation of protein kinase by vasopressin in renal medulla in situ.", "content": "Results of this study demonstrate that vasopressin activates protein kinase in intact renal medullary cells as detected by measurement of the (-cyclic AMP/+cyclic AMP) protein kinase activity ratios in freshly prepared tissue extracts (40,000 X g supernates) from bovine renal medullary slices. The activation of protein kinase was specific for vasopressin since parathyroid hormone, histamine, angiotensin II, or the inactive analog of vasopressin did not activate protein kinase. There was a direct correlation between the extent of protein kinase activation and the elevation in tissue levels of cyclic AMP elicited by increasing doses of vasopressin or with an increase in incubation time. The elevation of tissue cyclic AMP level and maximum activation of protein kinase reached maximum level at a vasopressin concentration of about 2 X 10(-9) M. Incubation of slices with vasopressin caused a dose-dependent decrease in the cyclic AMP-dependent protein kinase activity in the 40,000 X g supernate of homogenate from the renal medullary slices. This effect of vasopressin was specific for protein kinase since activity of lactate dehydrogenase or a specific [3H]colchicine-binding activity was not affected, and the decrease in the protein kinase was not due to the accumulation of a heat-stable protein kinase inhibitor. There was an increase in protein kinase was not due to the accumulation of a heat-stable protein kinase inhibitor. There was an increase in protein kinase activity extracted from 40,000 X g pellets of homogenate prepared from slices exposed to vasopressin. Results thus provide evidence that cyclic AMP-mediated protein kinase activation in the intact cells is an integral part of cellular response of the mammalian renal medulla to vasopressin.", "contents": "Regulation of protein kinase by vasopressin in renal medulla in situ. Results of this study demonstrate that vasopressin activates protein kinase in intact renal medullary cells as detected by measurement of the (-cyclic AMP/+cyclic AMP) protein kinase activity ratios in freshly prepared tissue extracts (40,000 X g supernates) from bovine renal medullary slices. The activation of protein kinase was specific for vasopressin since parathyroid hormone, histamine, angiotensin II, or the inactive analog of vasopressin did not activate protein kinase. There was a direct correlation between the extent of protein kinase activation and the elevation in tissue levels of cyclic AMP elicited by increasing doses of vasopressin or with an increase in incubation time. The elevation of tissue cyclic AMP level and maximum activation of protein kinase reached maximum level at a vasopressin concentration of about 2 X 10(-9) M. Incubation of slices with vasopressin caused a dose-dependent decrease in the cyclic AMP-dependent protein kinase activity in the 40,000 X g supernate of homogenate from the renal medullary slices. This effect of vasopressin was specific for protein kinase since activity of lactate dehydrogenase or a specific [3H]colchicine-binding activity was not affected, and the decrease in the protein kinase was not due to the accumulation of a heat-stable protein kinase inhibitor. There was an increase in protein kinase was not due to the accumulation of a heat-stable protein kinase inhibitor. There was an increase in protein kinase activity extracted from 40,000 X g pellets of homogenate prepared from slices exposed to vasopressin. Results thus provide evidence that cyclic AMP-mediated protein kinase activation in the intact cells is an integral part of cellular response of the mammalian renal medulla to vasopressin."}
{"id": "PMID:189621", "title": "Influence of mannitol on contractile responses of isolated perfused arteries.", "content": "The influence of hyperosmotic mannitol on vascular smooth muscle contractile responses was examined in isolated arterial preparations. Vasoconstrictor effects of norepinephrine (NE) and potassium chloride (K+) in the perfused central artery of the rabbit's ear and in perfused mesenteric arteries of cats were significantly inhibited by infusion with Krebs bicarbonate solution made hyperosmotic with mannitol (50-200 mosM increase). Similarly, the magnitude and duration of vasoconstrictor responses to transmural stimulation of the central ear artery of the rabbit were decreased by hyperosmotic mannitol (50 mosM). Mannitol (50 mosM) produced a decrease in perfusion pressure when perfusion pressure was maintained at an increased level by K+ (60 mM). Mannitol-induced vasodilatation was not affected by ethacrynic acid (1.5 X 10(-5) M), beta adrenergic blockade or by the development of tachyphylaxis to the vasodilator effects of nitroglycerin. The concentration of cyclic adenosine-monophosphate was not changed by mannitol. Isotonic mannitol also inhibited NE-induced contractile responses. These data indicate that hyperosmotic mannitol produces vasodilatation in isolated arterial smooth muscle by a mechanism(s) that appears dissimilar from that of several other vasodilator substances and suggest that hypertonicity may not be the only factor involved in the vasodilator effect of mannitol.", "contents": "Influence of mannitol on contractile responses of isolated perfused arteries. The influence of hyperosmotic mannitol on vascular smooth muscle contractile responses was examined in isolated arterial preparations. Vasoconstrictor effects of norepinephrine (NE) and potassium chloride (K+) in the perfused central artery of the rabbit's ear and in perfused mesenteric arteries of cats were significantly inhibited by infusion with Krebs bicarbonate solution made hyperosmotic with mannitol (50-200 mosM increase). Similarly, the magnitude and duration of vasoconstrictor responses to transmural stimulation of the central ear artery of the rabbit were decreased by hyperosmotic mannitol (50 mosM). Mannitol (50 mosM) produced a decrease in perfusion pressure when perfusion pressure was maintained at an increased level by K+ (60 mM). Mannitol-induced vasodilatation was not affected by ethacrynic acid (1.5 X 10(-5) M), beta adrenergic blockade or by the development of tachyphylaxis to the vasodilator effects of nitroglycerin. The concentration of cyclic adenosine-monophosphate was not changed by mannitol. Isotonic mannitol also inhibited NE-induced contractile responses. These data indicate that hyperosmotic mannitol produces vasodilatation in isolated arterial smooth muscle by a mechanism(s) that appears dissimilar from that of several other vasodilator substances and suggest that hypertonicity may not be the only factor involved in the vasodilator effect of mannitol."}
{"id": "PMID:189622", "title": "Physiological inhibition and facilitation of adrenocortical response to hemorrhage.", "content": "In a search for physiological feedback inhibition, secretion rates of cortisol were measured in intact dogs before and after sequential hemorrhages. The sucond of two sequential hemorrhages of 10 ml/kg separated by 90 min evoked significantly less increase of secretion rate of cortisol than did the first. This result was not explained by differential hemodynamic effects. Exhaustion of pituitary or adrenal capacities was excluded, since dogs responded normally to a second, larger hemorrhage. However, no attenuation response to a second 10 ml/kg hemorrhage was seen after a larger, 20 ml/kg, first hemorrhage. This led in turn to a search for a physiological facilitatory mechanism which might offset the feedback effect. The second of two rapid sequential hemorrhages to isovolemia following preexpansion of plasma volume evoked significantly greater increase of secretion rate of cortisol than did the first. This result also was not explained by differential hemodynamic effects. The results support the hypothesis that hemorrhage elicits both physiological feedback and facilitatory effects which interact and which are (different) functions of the intensity of stimulus.", "contents": "Physiological inhibition and facilitation of adrenocortical response to hemorrhage. In a search for physiological feedback inhibition, secretion rates of cortisol were measured in intact dogs before and after sequential hemorrhages. The sucond of two sequential hemorrhages of 10 ml/kg separated by 90 min evoked significantly less increase of secretion rate of cortisol than did the first. This result was not explained by differential hemodynamic effects. Exhaustion of pituitary or adrenal capacities was excluded, since dogs responded normally to a second, larger hemorrhage. However, no attenuation response to a second 10 ml/kg hemorrhage was seen after a larger, 20 ml/kg, first hemorrhage. This led in turn to a search for a physiological facilitatory mechanism which might offset the feedback effect. The second of two rapid sequential hemorrhages to isovolemia following preexpansion of plasma volume evoked significantly greater increase of secretion rate of cortisol than did the first. This result also was not explained by differential hemodynamic effects. The results support the hypothesis that hemorrhage elicits both physiological feedback and facilitatory effects which interact and which are (different) functions of the intensity of stimulus."}
{"id": "PMID:189623", "title": "Protriptyline: an effective agent in the treatment of the narcolepsy-cataplexy syndrome and hypersomnia.", "content": "The authors present five case reports illustrating that 10-20 mg of protriptyline in a single dose at bedtime can effectively control arousal dysfunction (sleep drunkenness and hypersomnia) and the narcolepsycataplexy syndrome without the apparent development of tolerance and without the side effects that are frequent complications of treatment with other agents. Although protriptyline was efficacious in controlling symptoms, it was found to have relatively poor REM sleep-suppressing properties.", "contents": "Protriptyline: an effective agent in the treatment of the narcolepsy-cataplexy syndrome and hypersomnia. The authors present five case reports illustrating that 10-20 mg of protriptyline in a single dose at bedtime can effectively control arousal dysfunction (sleep drunkenness and hypersomnia) and the narcolepsycataplexy syndrome without the apparent development of tolerance and without the side effects that are frequent complications of treatment with other agents. Although protriptyline was efficacious in controlling symptoms, it was found to have relatively poor REM sleep-suppressing properties."}
{"id": "PMID:189624", "title": "An integrated approach to tuberculosis care in the Commonwealth of Pennsylvania.", "content": "A significant economization of taxpayers resources (+5.5 million per year) is the result of a major restructuring of the tuberculosis control program in the Commonwealth of Pennsylvania. Concomitantly improved patient management has accelerated the decline in the incidence of tuberculosis while maintaining recommended federal performance standards. The reasons for the success in obtaining this high degree of efficiency are discussed.", "contents": "An integrated approach to tuberculosis care in the Commonwealth of Pennsylvania. A significant economization of taxpayers resources (+5.5 million per year) is the result of a major restructuring of the tuberculosis control program in the Commonwealth of Pennsylvania. Concomitantly improved patient management has accelerated the decline in the incidence of tuberculosis while maintaining recommended federal performance standards. The reasons for the success in obtaining this high degree of efficiency are discussed."}
{"id": "PMID:189626", "title": "Tumors of the submaxillary gland.", "content": "This study reviews a thirty year experience with 217 patients who had a tumor of the submaxillary gland, comprising about 9 per cent of all patients with salivary neoplasms seen during the same period. Most of the tumors were malignant (56 per cent), with adenoid cystic carcinoma predominating, but the histologic type most frequently encountered was benign mixed tumor (43 per cent). Median age was fifty-four years in patients with malignant tumors compared with forty-six years in those with benign tumors, and 58 per cent were women. Asymptomatic swelling was the usual presenting complaint, and the clinical findings are summarized using a staging system recently proposed for patients with parotid tumors. Cervical lymph node metastasis occurred in at least 50 per cent of patients who had an adenocarcinoma or epidermoid, mucoepidermoid, or anaplastic carcinoma. Treatment was surgical and complete gland excision proved adequate in those with benign tumors. Radical neck dissection was performed in conjunction with submaxillary resection in most patients with malignant lesions, but radical en bloc resection was reserved for those few who had extensive or fixed disease. Net determinate \"cure\" rates at five and ten years (30 and 20 per cent, respectively) are distressingly low and compare unfavorably with those previously reported in patients treated for carcinoma of the parotid. The high local recurrence rate and the greater incidence in the submaxillary gland of more aggressive tumor types which metastasize readily suggest that current treatment should be more radical. It seems reasonable to expect that results might be improved if en bloc resections were more often performed in patients with less advanced disease, possibly in conjuction with intensive postoperative irradiation in selected cases.", "contents": "Tumors of the submaxillary gland. This study reviews a thirty year experience with 217 patients who had a tumor of the submaxillary gland, comprising about 9 per cent of all patients with salivary neoplasms seen during the same period. Most of the tumors were malignant (56 per cent), with adenoid cystic carcinoma predominating, but the histologic type most frequently encountered was benign mixed tumor (43 per cent). Median age was fifty-four years in patients with malignant tumors compared with forty-six years in those with benign tumors, and 58 per cent were women. Asymptomatic swelling was the usual presenting complaint, and the clinical findings are summarized using a staging system recently proposed for patients with parotid tumors. Cervical lymph node metastasis occurred in at least 50 per cent of patients who had an adenocarcinoma or epidermoid, mucoepidermoid, or anaplastic carcinoma. Treatment was surgical and complete gland excision proved adequate in those with benign tumors. Radical neck dissection was performed in conjunction with submaxillary resection in most patients with malignant lesions, but radical en bloc resection was reserved for those few who had extensive or fixed disease. Net determinate \"cure\" rates at five and ten years (30 and 20 per cent, respectively) are distressingly low and compare unfavorably with those previously reported in patients treated for carcinoma of the parotid. The high local recurrence rate and the greater incidence in the submaxillary gland of more aggressive tumor types which metastasize readily suggest that current treatment should be more radical. It seems reasonable to expect that results might be improved if en bloc resections were more often performed in patients with less advanced disease, possibly in conjuction with intensive postoperative irradiation in selected cases."}
{"id": "PMID:189627", "title": "Parotid tumors in children.", "content": "Most salivary gland tumors, both benign and malignant, develop within the parotid glands. Although an overwhelming majority of tumors are reported in the adult population, the parotid glands are also the most frequently involved salivary glands in the pediatric age group. This study represents a combination of case material from the Armed Forces Institute of Pathology and our personal experiences. Of approximately 10,000 salivary gland lesions accessioned in all ages, only 124 tumors occurred in the parotid gland in children less than fifteen years old. There were ninety benign and thirty-four malignant lesions. The two most common benign masses were mixed tumors and vascular lesions. The most common malignancies were the mucoepidermoid and acinic cell carcinomas. We recommended that all solid tumors be removed by parotidectomy.", "contents": "Parotid tumors in children. Most salivary gland tumors, both benign and malignant, develop within the parotid glands. Although an overwhelming majority of tumors are reported in the adult population, the parotid glands are also the most frequently involved salivary glands in the pediatric age group. This study represents a combination of case material from the Armed Forces Institute of Pathology and our personal experiences. Of approximately 10,000 salivary gland lesions accessioned in all ages, only 124 tumors occurred in the parotid gland in children less than fifteen years old. There were ninety benign and thirty-four malignant lesions. The two most common benign masses were mixed tumors and vascular lesions. The most common malignancies were the mucoepidermoid and acinic cell carcinomas. We recommended that all solid tumors be removed by parotidectomy."}
{"id": "PMID:189628", "title": "Viral-specific humoral immunity to herpes simplex-induced antigens in patients with squamous carcinoma of the head and neck.", "content": "Serum antibodies to herpes simplex virus-induced antigens (HSVIA) were quantitated in 122 patients with head and neck squamous carcinoma, 93 patients tumor-free after treatment for these malignant lesions, 27 patients with nonsquamous malignant lesions, 30 heavy smokers, and 36 nonsmokers. Serum IgA anti-HSVIA antibodies were detected in a greater percentage of sera of patients with squamous carcinoma (61 per cent), patients previously treated for these malignant lesions (56 per cent), and heavy smokers (57 per cent) than in patients with nonsquamous malignant lesions (11 per cent) or nonsmokers (8 per cent). Furthermore, titers of these antibodies were higher in patients with squamous carcinoma than in smokers. In patients tumor-free more than three years after treatment, the percentage of positive sera was significantly lower than that in untreated patients and in patients three years or less after treatment. This study demonstrates for the first time a high frequency of antibodies to HSV-induced antigens confined to subjects at high risk of developing head and neck squamous carcinoma and in patients with these malignancies as well as a correlation between the levels of these antibodies and clinical course after treatment.", "contents": "Viral-specific humoral immunity to herpes simplex-induced antigens in patients with squamous carcinoma of the head and neck. Serum antibodies to herpes simplex virus-induced antigens (HSVIA) were quantitated in 122 patients with head and neck squamous carcinoma, 93 patients tumor-free after treatment for these malignant lesions, 27 patients with nonsquamous malignant lesions, 30 heavy smokers, and 36 nonsmokers. Serum IgA anti-HSVIA antibodies were detected in a greater percentage of sera of patients with squamous carcinoma (61 per cent), patients previously treated for these malignant lesions (56 per cent), and heavy smokers (57 per cent) than in patients with nonsquamous malignant lesions (11 per cent) or nonsmokers (8 per cent). Furthermore, titers of these antibodies were higher in patients with squamous carcinoma than in smokers. In patients tumor-free more than three years after treatment, the percentage of positive sera was significantly lower than that in untreated patients and in patients three years or less after treatment. This study demonstrates for the first time a high frequency of antibodies to HSV-induced antigens confined to subjects at high risk of developing head and neck squamous carcinoma and in patients with these malignancies as well as a correlation between the levels of these antibodies and clinical course after treatment."}
{"id": "PMID:189629", "title": "Adenyl cyclase and cyclic AMP (cAMP) in acute experimental pancreatitis.", "content": "The level of adenosine 3':5'-cyclic monophosphate (cAMP) and the activity of adenyl cyclase were studied in the pancreas under normal conditions and during acute hemorrhagic pancreatitis induced by intraductal injection of fresh trypsin-bile-blood mixture. In addition, the adenyl cyclase was localized histochemically in the pancreas. Basal cAMP concentration and adenyl cyclase activity were 0.88 +/- 0.11 pmoles/mg wet tissue and 3.39 +/- 0.21 pmoles/mg protein/min, respectively. The acute pancreatitis drastically reduced the adenyl cyclase activity at 15 minutes to 1.66 +/- 0.54 pmoles/mg protein/min, and totally suppressed adenyl cyclase activity at 30 minutes after the onset of pancreatitis without affecting cAMP levels. The presence of sodium fluoride in the incubation medium prolonged the enzyme activity up to 45 minutes. The progressive disappearance of adenyl cyclase activity presumably resulted from the destruction of cellular integrity caused by autodigestion by the active proteolytic enzymes released during pancreatitis.", "contents": "Adenyl cyclase and cyclic AMP (cAMP) in acute experimental pancreatitis. The level of adenosine 3':5'-cyclic monophosphate (cAMP) and the activity of adenyl cyclase were studied in the pancreas under normal conditions and during acute hemorrhagic pancreatitis induced by intraductal injection of fresh trypsin-bile-blood mixture. In addition, the adenyl cyclase was localized histochemically in the pancreas. Basal cAMP concentration and adenyl cyclase activity were 0.88 +/- 0.11 pmoles/mg wet tissue and 3.39 +/- 0.21 pmoles/mg protein/min, respectively. The acute pancreatitis drastically reduced the adenyl cyclase activity at 15 minutes to 1.66 +/- 0.54 pmoles/mg protein/min, and totally suppressed adenyl cyclase activity at 30 minutes after the onset of pancreatitis without affecting cAMP levels. The presence of sodium fluoride in the incubation medium prolonged the enzyme activity up to 45 minutes. The progressive disappearance of adenyl cyclase activity presumably resulted from the destruction of cellular integrity caused by autodigestion by the active proteolytic enzymes released during pancreatitis."}
{"id": "PMID:189630", "title": "Common bile duct obstruction by hepatoma.", "content": "Two cases of hepatoma are presented in which the clinical manifestations of biliary obstruction resulted from growth of hepatoma into the extrahepatic bile duct. Recognition of such a manifestation of the hepatoma may allow for surgical extirpation of the tumor combined with radiation therapy, which may result in long survival.", "contents": "Common bile duct obstruction by hepatoma. Two cases of hepatoma are presented in which the clinical manifestations of biliary obstruction resulted from growth of hepatoma into the extrahepatic bile duct. Recognition of such a manifestation of the hepatoma may allow for surgical extirpation of the tumor combined with radiation therapy, which may result in long survival."}
{"id": "PMID:189637", "title": "Effects of pharmacologic alterations of adrenergic mechanisms by cocaine, tropolone, aminophylline, and ketamine on epinephrine-induced arrhythmias during halothane-nitrous oxide anesthesia.", "content": "The purpose of this study was to examine the effects of pharmacologic alterations of adrenergic terminating mechanisms by cocaine, tropolone, aminophylline, and ketamine on the ability of epinephrine to induce arrhythmias during halothane-nitrous oxide anesthesia in dogs. Because the first three drugs inhibit intraneuronal uptake of catecholamines, extraneuronal catechol-O-methyl transferase (COMT), and phosphodiesterase, respectively, they might be expected to potentiate epinephrine-induced arrhythmias. To evaluate this possibility, the authors devised a technique for determining the minimal arrhythmic dosage of epinephrine that permitted graded assessment of changes in the sensitivity of the heart to epinephrine-induced arrhythmias. When the first three drugs were administered to the same dog in the order listed at intervals of 60 minutes, they sequentially increased the ability of epinephrine to induce arrhythmias. Ketamine, according to several investigators, also appears to block reuptake of catecholamines, and when studied was also found to enhance the arrhythmogenicity of epinephrine. The extent of enhancement was comparable to that seen with cocaine. These results indicate that drugs like cocaine and ketamine that interfere with intraneuronal uptake can facilitate the development of epinephrine-induced arrhythmias and that the successive pharmacologic interference of intraneuron uptake, COMT, and phosphodiesterase leads to a stepwise increase in the arrhythmogenicity of epinephrine.", "contents": "Effects of pharmacologic alterations of adrenergic mechanisms by cocaine, tropolone, aminophylline, and ketamine on epinephrine-induced arrhythmias during halothane-nitrous oxide anesthesia. The purpose of this study was to examine the effects of pharmacologic alterations of adrenergic terminating mechanisms by cocaine, tropolone, aminophylline, and ketamine on the ability of epinephrine to induce arrhythmias during halothane-nitrous oxide anesthesia in dogs. Because the first three drugs inhibit intraneuronal uptake of catecholamines, extraneuronal catechol-O-methyl transferase (COMT), and phosphodiesterase, respectively, they might be expected to potentiate epinephrine-induced arrhythmias. To evaluate this possibility, the authors devised a technique for determining the minimal arrhythmic dosage of epinephrine that permitted graded assessment of changes in the sensitivity of the heart to epinephrine-induced arrhythmias. When the first three drugs were administered to the same dog in the order listed at intervals of 60 minutes, they sequentially increased the ability of epinephrine to induce arrhythmias. Ketamine, according to several investigators, also appears to block reuptake of catecholamines, and when studied was also found to enhance the arrhythmogenicity of epinephrine. The extent of enhancement was comparable to that seen with cocaine. These results indicate that drugs like cocaine and ketamine that interfere with intraneuronal uptake can facilitate the development of epinephrine-induced arrhythmias and that the successive pharmacologic interference of intraneuron uptake, COMT, and phosphodiesterase leads to a stepwise increase in the arrhythmogenicity of epinephrine."}
{"id": "PMID:189640", "title": "Serum triglyceride and cholesterol levels and lipid electrophoretic patterns in intrinsic and extrinsic allergic states.", "content": "This study indicates that hypertriglyceridemia and associated pre-beta hyperlipidemia (Fredrickson's type IV lipid pattern) is frequently associated with intrinsic allergic disease characterized by chemical intolerant (hypersensitivity) states, particularly of the aspirin intolerant type and to a somewhat lesser extent with the butylated hydroxyanisole and butylated hydroxytoluene intolerant type, as well as the iodide intolerant state. It confirms that diabetics suffering concomitantly with extrinsic or intrinsic allergic disease still continue to demonstrate a high occurrence of this type of hypertriglyceridemia. In contrast, pure atopic, extrinsic-allergic patients demonstrated a very low incidence of type IV hyperlipoproteinemia. The interrelationships of these findings with previously reported metabolic abnormalities in intrinsic allergic hypersensitivity states is correlated.", "contents": "Serum triglyceride and cholesterol levels and lipid electrophoretic patterns in intrinsic and extrinsic allergic states. This study indicates that hypertriglyceridemia and associated pre-beta hyperlipidemia (Fredrickson's type IV lipid pattern) is frequently associated with intrinsic allergic disease characterized by chemical intolerant (hypersensitivity) states, particularly of the aspirin intolerant type and to a somewhat lesser extent with the butylated hydroxyanisole and butylated hydroxytoluene intolerant type, as well as the iodide intolerant state. It confirms that diabetics suffering concomitantly with extrinsic or intrinsic allergic disease still continue to demonstrate a high occurrence of this type of hypertriglyceridemia. In contrast, pure atopic, extrinsic-allergic patients demonstrated a very low incidence of type IV hyperlipoproteinemia. The interrelationships of these findings with previously reported metabolic abnormalities in intrinsic allergic hypersensitivity states is correlated."}
{"id": "PMID:189641", "title": "[Analysis of lipoproteins using polyacrylamide gel electrophoresis and fractionated precipitation with polyanions and detergents. Use in the classification of hyperlipoproteinemias].", "content": "Sodium dodecylsulphate precipitates very low density lipoproteins (VLDL and chylomicrons) rich in triglyceride and a narrow correlation (r = 0.9) was found between the turbidimetric index SDS and triglyceridemia. Heparin in calcium medium acts in the same way and precipitates also low density lipoproteins (LDL) rich in cholesterol. A correlation (r = 0.875) was drawn up between the cholesterol LDL and the difference between the turbidimetric indices (heparin Ca -- SDS). In the first case, we were thus measuring by turbidimetry a VLDL + chylomicron index and, in the second case, an LDL index which permits one to obtain simplified typing of the hyperlipoproteinemias. A nomogram linking the two indices of hyperlipoproteinemia type was drawn up experimentally. This orientation analysis may be completed by electrophoresis on polyacrylamide gel used in concentration gradient and pH. In the system proposed, the lipoproteins were previously stained with tetrazolium nitroblue and clearly shown up. The chylomicrons in particular, become separated from the VLDL, the sinking pre-beta-lipoprotein or Lp (a) was identifiable and the type III hyperlipemia was easily diagnosed.", "contents": "[Analysis of lipoproteins using polyacrylamide gel electrophoresis and fractionated precipitation with polyanions and detergents. Use in the classification of hyperlipoproteinemias]. Sodium dodecylsulphate precipitates very low density lipoproteins (VLDL and chylomicrons) rich in triglyceride and a narrow correlation (r = 0.9) was found between the turbidimetric index SDS and triglyceridemia. Heparin in calcium medium acts in the same way and precipitates also low density lipoproteins (LDL) rich in cholesterol. A correlation (r = 0.875) was drawn up between the cholesterol LDL and the difference between the turbidimetric indices (heparin Ca -- SDS). In the first case, we were thus measuring by turbidimetry a VLDL + chylomicron index and, in the second case, an LDL index which permits one to obtain simplified typing of the hyperlipoproteinemias. A nomogram linking the two indices of hyperlipoproteinemia type was drawn up experimentally. This orientation analysis may be completed by electrophoresis on polyacrylamide gel used in concentration gradient and pH. In the system proposed, the lipoproteins were previously stained with tetrazolium nitroblue and clearly shown up. The chylomicrons in particular, become separated from the VLDL, the sinking pre-beta-lipoprotein or Lp (a) was identifiable and the type III hyperlipemia was easily diagnosed."}
{"id": "PMID:189642", "title": "[Thyroid gland TSH receptors].", "content": "The author first considers the general conditions of reversibility, saturability, specificity and affinity which should be filled by all receptors, but emphasizes certain special difficulties on analysis of TSH receptors. TSH is a glycoprotein of molecular weight 28,000, composed of 2 alpha and beta sub-units; the role of each of these with regard to the receptor, is discussed. The TSH receptor is mainly localised in the outer part of the plasma membrane of the thyroid cells. An important point concerns the biological significance of the link between TSH and receptors and the activation of the adenylate cyclase AMPc system. One may experimentally dissociate with lecithinase these two cell events: treatment of thyroid tissue with this enzyme abolishes the biological response but does not affect the bond. The notion of hormone dependency of thyroid carcinoma is still classical but should be reconsidered in the light of new data concerning TSH receptors. Finally, the notion of variable receptivity of the thyroid tissue to TSH permits one to imagine another regulatory mechanism for which the receptors are responsible.", "contents": "[Thyroid gland TSH receptors]. The author first considers the general conditions of reversibility, saturability, specificity and affinity which should be filled by all receptors, but emphasizes certain special difficulties on analysis of TSH receptors. TSH is a glycoprotein of molecular weight 28,000, composed of 2 alpha and beta sub-units; the role of each of these with regard to the receptor, is discussed. The TSH receptor is mainly localised in the outer part of the plasma membrane of the thyroid cells. An important point concerns the biological significance of the link between TSH and receptors and the activation of the adenylate cyclase AMPc system. One may experimentally dissociate with lecithinase these two cell events: treatment of thyroid tissue with this enzyme abolishes the biological response but does not affect the bond. The notion of hormone dependency of thyroid carcinoma is still classical but should be reconsidered in the light of new data concerning TSH receptors. Finally, the notion of variable receptivity of the thyroid tissue to TSH permits one to imagine another regulatory mechanism for which the receptors are responsible."}
{"id": "PMID:189643", "title": "[Glucagon receptors].", "content": "The lecturer recalls the discovery of glucagon receptors in liver cell membranes, the role of the adenylate cyclase-AMPc system, until recent attempts at purification and isolation of this receptor. He then reviews successively, the problems of estimation, specificity of the interaction, the effects of purine and pyrimidine nucleotides on glucagon receptor interaction, etc. The importance of the two nucleotides GTP and ATP in activation of adenylate cyclase is emphasized. The VIP receptors (\"vasoactive intestinal peptide\") and secretin receptors are also discussed. In some ways, they resemble glucagon receptors. The possible consequences of these discoveries arethen discussed.", "contents": "[Glucagon receptors]. The lecturer recalls the discovery of glucagon receptors in liver cell membranes, the role of the adenylate cyclase-AMPc system, until recent attempts at purification and isolation of this receptor. He then reviews successively, the problems of estimation, specificity of the interaction, the effects of purine and pyrimidine nucleotides on glucagon receptor interaction, etc. The importance of the two nucleotides GTP and ATP in activation of adenylate cyclase is emphasized. The VIP receptors (\"vasoactive intestinal peptide\") and secretin receptors are also discussed. In some ways, they resemble glucagon receptors. The possible consequences of these discoveries arethen discussed."}
{"id": "PMID:189644", "title": "[Variations of membrane hormonal receptors induced by their ligands].", "content": "A great deal of research has been carried out on hormonal receptors and their quantitative variations, in particular, those which may be induced by their ligands. Insulin receptors, growth hormone, TRH and catecholamine receptors are already good examples of these variations. The authors have particularly studied angiotensin receptors which also vary with the plasma concentration of the hormone. Numerous questions of molecular biology are raised by these observations and are then discussed. The possible consequences of these discoveries on the physiopathology of endocrine diseases are finally discussed.", "contents": "[Variations of membrane hormonal receptors induced by their ligands]. A great deal of research has been carried out on hormonal receptors and their quantitative variations, in particular, those which may be induced by their ligands. Insulin receptors, growth hormone, TRH and catecholamine receptors are already good examples of these variations. The authors have particularly studied angiotensin receptors which also vary with the plasma concentration of the hormone. Numerous questions of molecular biology are raised by these observations and are then discussed. The possible consequences of these discoveries on the physiopathology of endocrine diseases are finally discussed."}
{"id": "PMID:189645", "title": "In vitro cytotoxicity of serum and peripheral blood leukocytes for equine herpesvirus type 1-infected target cells.", "content": "The immune response in horses following experimental infection with equine herpesvirus type 1 (EHV-1) was assessed by measuring cytotoxicity for EHV-1-infected target cells. A technique was developed, using [125I]5-iodo-2'-deoxyuridine ([125I]IUDR)-labeled equine fetal kidney cells infected with EHV-1 as the target cells. It was shown that peripheral blood leukocytes from a recovered horse were capable of lysing target cells, as measured by the loss of radio-active label. Following the experimental infection of specific-pathogen-free ponies with EHV-1, cytotoxicity was obtained with fresh autologous serum, peripheral blood leukocytes in autologous serum, and washed peripheral blood leukocytes. Cytotoxicity of the serum and peripheral blood leukocytes was detected as early as one day after infection. It is suggested that cytotoxic antibodies or cells could play an important part in restricting virus spread after infection of the horse with EHV-1.", "contents": "In vitro cytotoxicity of serum and peripheral blood leukocytes for equine herpesvirus type 1-infected target cells. The immune response in horses following experimental infection with equine herpesvirus type 1 (EHV-1) was assessed by measuring cytotoxicity for EHV-1-infected target cells. A technique was developed, using [125I]5-iodo-2'-deoxyuridine ([125I]IUDR)-labeled equine fetal kidney cells infected with EHV-1 as the target cells. It was shown that peripheral blood leukocytes from a recovered horse were capable of lysing target cells, as measured by the loss of radio-active label. Following the experimental infection of specific-pathogen-free ponies with EHV-1, cytotoxicity was obtained with fresh autologous serum, peripheral blood leukocytes in autologous serum, and washed peripheral blood leukocytes. Cytotoxicity of the serum and peripheral blood leukocytes was detected as early as one day after infection. It is suggested that cytotoxic antibodies or cells could play an important part in restricting virus spread after infection of the horse with EHV-1."}
{"id": "PMID:189646", "title": "Immune electron microscopy of transmissible gastroenteritis virus and rotavirus (reovirus-like agent) of swine.", "content": "Immune electron microscopy (IEM) was developed as a diagnostic aid for detecting and identifying transmissible gastroenteritis virus and rotavirus (reovirus-like agent) in fecal and intestinal contents from cases of gastroenteritis in young pigs. Variables involved in use of direct IEM and its sensitivity were determined. Aggregates of virus coated with specific antibody were seen in virus samples mixed with homologous convalescent antiserum, but not in control samples containing preexposure serum or antibody directed against a heterologous virus. At least a ten fold enhancement of the sensitivity of direct IEM for virus detection was accomplished using indirect IEM employing rabbit anti-porcine IgG to further aggregate virus-antibody complexes. The technique was used to investigate the size and morphology of the porcine rotavirus. Particles ranged from 55 to 70 nm in diameter and had capsomere structures. Morphologically, the porcine rotavirus resembled the calf and human rotaviruses. By IEM, employing specific antiserums for each virus, porcine rotavirus was found to be antigenically related to these 2 viruses, but not to the reovirus type 3.", "contents": "Immune electron microscopy of transmissible gastroenteritis virus and rotavirus (reovirus-like agent) of swine. Immune electron microscopy (IEM) was developed as a diagnostic aid for detecting and identifying transmissible gastroenteritis virus and rotavirus (reovirus-like agent) in fecal and intestinal contents from cases of gastroenteritis in young pigs. Variables involved in use of direct IEM and its sensitivity were determined. Aggregates of virus coated with specific antibody were seen in virus samples mixed with homologous convalescent antiserum, but not in control samples containing preexposure serum or antibody directed against a heterologous virus. At least a ten fold enhancement of the sensitivity of direct IEM for virus detection was accomplished using indirect IEM employing rabbit anti-porcine IgG to further aggregate virus-antibody complexes. The technique was used to investigate the size and morphology of the porcine rotavirus. Particles ranged from 55 to 70 nm in diameter and had capsomere structures. Morphologically, the porcine rotavirus resembled the calf and human rotaviruses. By IEM, employing specific antiserums for each virus, porcine rotavirus was found to be antigenically related to these 2 viruses, but not to the reovirus type 3."}
{"id": "PMID:189647", "title": "Isolation of feline leukemia virus from clinical specimens.", "content": "Specimens obtained from feline leukemia virus (FeLV)-positive cats were examined for infectious FeLV. Feline leukemia virus was detected by a focus-forming assay and confirmed by florescent antibody. Techniques of sample processing were evaluated and adjusted for optimum detection of FeLV. Low levels of FeLV were detected in 2 of 10 oral samples; however, the majority of these samples (17 of 27 tested) produced cytopathic effects in tissue culture which prevented Fe LV detection. Three of 24 urine samples and 1 of 20 rectal specimens were positive for FeLV. One milk sample contained high levels of FeLV.", "contents": "Isolation of feline leukemia virus from clinical specimens. Specimens obtained from feline leukemia virus (FeLV)-positive cats were examined for infectious FeLV. Feline leukemia virus was detected by a focus-forming assay and confirmed by florescent antibody. Techniques of sample processing were evaluated and adjusted for optimum detection of FeLV. Low levels of FeLV were detected in 2 of 10 oral samples; however, the majority of these samples (17 of 27 tested) produced cytopathic effects in tissue culture which prevented Fe LV detection. Three of 24 urine samples and 1 of 20 rectal specimens were positive for FeLV. One milk sample contained high levels of FeLV."}
{"id": "PMID:189648", "title": "Cultural and biochemical criteria for the identification of haemophilus spp from swine.", "content": "Twenty-two Haemophilus cultures of types prevalent in swine and of different geographic origins were subjected to biochemical and cultural examinations. Three subgroups were identified: One was unrease-positive, produced porphyrin from delta-aminolevulinic acid, and grew on infusion mediums supplemented only with V factor; the 2nd was unrease-negative, porphyrin-positive, and grew only on serum-enriched mediums with added V factor; and the 3rd was unrease-negative, porphyrin-negative, and grew only on serum-enriched mediums with added V and X factors. The groups generally corresponded to Haemophilus parahaemolyticus, Haemophilus parasuis, and Haemophilus suis, respectively. By means of the unrease and porphyrin tests, it was possible to assign, presumptively, porcine haemophilus cultures to 1 of the 3 species. Other tests, such as beta-galactosidase, hemolysis, and fermentation of carbohydrates were of secondary value in differentiating between these species.", "contents": "Cultural and biochemical criteria for the identification of haemophilus spp from swine. Twenty-two Haemophilus cultures of types prevalent in swine and of different geographic origins were subjected to biochemical and cultural examinations. Three subgroups were identified: One was unrease-positive, produced porphyrin from delta-aminolevulinic acid, and grew on infusion mediums supplemented only with V factor; the 2nd was unrease-negative, porphyrin-positive, and grew only on serum-enriched mediums with added V factor; and the 3rd was unrease-negative, porphyrin-negative, and grew only on serum-enriched mediums with added V and X factors. The groups generally corresponded to Haemophilus parahaemolyticus, Haemophilus parasuis, and Haemophilus suis, respectively. By means of the unrease and porphyrin tests, it was possible to assign, presumptively, porcine haemophilus cultures to 1 of the 3 species. Other tests, such as beta-galactosidase, hemolysis, and fermentation of carbohydrates were of secondary value in differentiating between these species."}
{"id": "PMID:189649", "title": "Demonstration of an avian adenovirus as the causative agent of marble spleen disease.", "content": "A purification procedure, using chloroform or fluorocarbon extraction and centrifugation on a cushion of cesium chloride (CsCL), was designed to isolate the causative virus of marble spleen disease. Virus was purified, inoculated into turkeys, and subsequently reisolated by purification from the spleen of inoculated turkeys, thus fulfilling Koch's postulates. Splenic antigen was detected by the agar gel precipitin test, and viral inclusions with viral particles were observed by light and electron microscopy. Results of further studies indicated splenic lymphoreticulum cell hyperplasia was a sensitive indicator of marble spleen disease virus (MSDV) infection. Direct fluorescent antibody staining revealed nuclear fluorescence in virus-infected splenic cells from turkeys inoculated with purified MSDV. With negative stain electron microscopy, MSDV was observed to be 90 nm across with an icosahedral capsid composed of 252 capsomeres. This morphologic feature was consistent with that of an avian adenovirus. Serologic evidence for classification of MSDV  as an adenovirus was the cross reaction of MSDV antigen with antiserum to turkey adenovirus serotypes TA-1 and TA-2 in the agar gel precipitin test.", "contents": "Demonstration of an avian adenovirus as the causative agent of marble spleen disease. A purification procedure, using chloroform or fluorocarbon extraction and centrifugation on a cushion of cesium chloride (CsCL), was designed to isolate the causative virus of marble spleen disease. Virus was purified, inoculated into turkeys, and subsequently reisolated by purification from the spleen of inoculated turkeys, thus fulfilling Koch's postulates. Splenic antigen was detected by the agar gel precipitin test, and viral inclusions with viral particles were observed by light and electron microscopy. Results of further studies indicated splenic lymphoreticulum cell hyperplasia was a sensitive indicator of marble spleen disease virus (MSDV) infection. Direct fluorescent antibody staining revealed nuclear fluorescence in virus-infected splenic cells from turkeys inoculated with purified MSDV. With negative stain electron microscopy, MSDV was observed to be 90 nm across with an icosahedral capsid composed of 252 capsomeres. This morphologic feature was consistent with that of an avian adenovirus. Serologic evidence for classification of MSDV  as an adenovirus was the cross reaction of MSDV antigen with antiserum to turkey adenovirus serotypes TA-1 and TA-2 in the agar gel precipitin test."}
{"id": "PMID:189650", "title": "[Tumors of the endodermal sinus (author's transl)].", "content": "Seven cases of tumors of the endodermal sinus are reviewed. This is a highly malignant germinal tumor, arisen from extraembrionary cell differentiation. It is different both biologically and pathologically from sacrocoxigeal teratoma. There are no survivors in these series. All seven patients have been surgically treated chemotherapy has been used in four, and X-ray therapy in two. It is noteworthy that alpha-phetoprotein is present in patients with this type of tumor. This fact can be used both in diagnosis of the tumor and of its recurrence.", "contents": "[Tumors of the endodermal sinus (author's transl)]. Seven cases of tumors of the endodermal sinus are reviewed. This is a highly malignant germinal tumor, arisen from extraembrionary cell differentiation. It is different both biologically and pathologically from sacrocoxigeal teratoma. There are no survivors in these series. All seven patients have been surgically treated chemotherapy has been used in four, and X-ray therapy in two. It is noteworthy that alpha-phetoprotein is present in patients with this type of tumor. This fact can be used both in diagnosis of the tumor and of its recurrence."}
{"id": "PMID:189651", "title": "[Virilizing adrenal carcinoma (author's transl)].", "content": "A case of virilizing adrenal carcinoma, diagnosed in the first year of age, is presented. The difficulties of differential diagnosis with congenital adrenal hyperplasia are briefly discressed. There is not evidence of metastasis 15 months after complete surgical excision of the tumor and repeated detreminations of 17-CO and 17-OH have remained within normal limits. Finally some considerations are made regarding diagnosis, prognosis and treatment.", "contents": "[Virilizing adrenal carcinoma (author's transl)]. A case of virilizing adrenal carcinoma, diagnosed in the first year of age, is presented. The difficulties of differential diagnosis with congenital adrenal hyperplasia are briefly discressed. There is not evidence of metastasis 15 months after complete surgical excision of the tumor and repeated detreminations of 17-CO and 17-OH have remained within normal limits. Finally some considerations are made regarding diagnosis, prognosis and treatment."}
{"id": "PMID:189652", "title": "[Testicular tumours in infancy (author's transl)].", "content": "Eleven tumours of the testis are presented. Treatment is based in: surgery (gonadectomie and paraaortical lymphadenectomie), quimiotherapy, depending of its pathological pattern and in some cases radiotherapy. In methastasis, surgery if it is possible and poliquimiotherapy. Total mortality rate is 22% (2/11). The follow up is from two to seven years.", "contents": "[Testicular tumours in infancy (author's transl)]. Eleven tumours of the testis are presented. Treatment is based in: surgery (gonadectomie and paraaortical lymphadenectomie), quimiotherapy, depending of its pathological pattern and in some cases radiotherapy. In methastasis, surgery if it is possible and poliquimiotherapy. Total mortality rate is 22% (2/11). The follow up is from two to seven years."}
{"id": "PMID:189653", "title": "[Nephroblastoma on a horse-shoe kidney].", "content": "A female child, 5 years 10/12 old, is presented with a nephroblastoma inserted on a horse-shoe kidney. She is in a satisfactory state 14 months after surgery. The authors emphasize the favorable outcome with a treatment of combined surgery, radiotherapy and vincristine.", "contents": "[Nephroblastoma on a horse-shoe kidney]. A female child, 5 years 10/12 old, is presented with a nephroblastoma inserted on a horse-shoe kidney. She is in a satisfactory state 14 months after surgery. The authors emphasize the favorable outcome with a treatment of combined surgery, radiotherapy and vincristine."}
{"id": "PMID:189655", "title": "Trial and study on nephroblastomas S.I.O.P. No. 1.", "content": "The International Society of Paediatric Oncology (S.I.O.P.) organised a study and trial on nephroblastomas in September 1971. This first trial was stopped in October 1974. In this period, 398 patients were included in trial and study. Patients came from 42 Centres in 14 countries. Eligible for the clinical trial were 195 patients. The clinical trial consisted of 2 parts: Part 1. Radiotherapy: Pre- and post-operative radiotherapy versus post-operative radiotherapy alone. Part 2. Chemotherapy: One single course of actinomycin D versus multiple courses of actinomycin D. For the radiotherapy trial, 137 cases were suitable after randomization. Concerning the recurrence-free survival, there were no significant differences following the actuarial statistical method. The same for survival. There was a high rate of ruptures in the post-operative group. These ruptured cases caused a higher rate of metastases and asked for a heavier treatment. Especially because of these ruptured cases the conclusion is drawn that pre- and post-operative radiotherapy is a better way of treatment for nephroblastomas when they cannot be expected to be a stage I tumour on clinical grounds. For the chemotherapy trial, 160 cases were suitable. There was no difference between the group of patients receiving a single course versus multiple courses of actinomycin D. Disease-free interval and survival in both groups in all stages were the same. The conclusion is drawn that this way of treatmetn does not make any difference. In a second study, chemotherapy with two agents is considered in two groups of patients receiving 6 months chemotherapy vincristine and actinomycin D versus 15 months.", "contents": "Trial and study on nephroblastomas S.I.O.P. No. 1. The International Society of Paediatric Oncology (S.I.O.P.) organised a study and trial on nephroblastomas in September 1971. This first trial was stopped in October 1974. In this period, 398 patients were included in trial and study. Patients came from 42 Centres in 14 countries. Eligible for the clinical trial were 195 patients. The clinical trial consisted of 2 parts: Part 1. Radiotherapy: Pre- and post-operative radiotherapy versus post-operative radiotherapy alone. Part 2. Chemotherapy: One single course of actinomycin D versus multiple courses of actinomycin D. For the radiotherapy trial, 137 cases were suitable after randomization. Concerning the recurrence-free survival, there were no significant differences following the actuarial statistical method. The same for survival. There was a high rate of ruptures in the post-operative group. These ruptured cases caused a higher rate of metastases and asked for a heavier treatment. Especially because of these ruptured cases the conclusion is drawn that pre- and post-operative radiotherapy is a better way of treatment for nephroblastomas when they cannot be expected to be a stage I tumour on clinical grounds. For the chemotherapy trial, 160 cases were suitable. There was no difference between the group of patients receiving a single course versus multiple courses of actinomycin D. Disease-free interval and survival in both groups in all stages were the same. The conclusion is drawn that this way of treatmetn does not make any difference. In a second study, chemotherapy with two agents is considered in two groups of patients receiving 6 months chemotherapy vincristine and actinomycin D versus 15 months."}
{"id": "PMID:189656", "title": "[A case of hepatocarcinoma (author's transl)].", "content": "A case of hepatocarcinoma is presented in a five year old male treated with right hemihepatectomy and chemotherapy has been followed during nine months. The rarity of this histologic variety in childhood is emphasized, and so are the clinical, biological and pathological features.", "contents": "[A case of hepatocarcinoma (author's transl)]. A case of hepatocarcinoma is presented in a five year old male treated with right hemihepatectomy and chemotherapy has been followed during nine months. The rarity of this histologic variety in childhood is emphasized, and so are the clinical, biological and pathological features."}
{"id": "PMID:189658", "title": "Regression and progression of early femoral atherosclerosis in treated hyperlipoproteinemic patients.", "content": "Femoral angiograms were done to evaluate change in early atherosclerosis in 12 patients with type IV hyperlipoproteinemia and 13 with type II hyperlipoproteinemia. The patients' average age was 48 years; only one had claudication. Elevated blood lipids and blood pressure were treated with drugs and diet. Repeat angiograms after an interval of 13 months showed regression of atherosclerosis in nine patients, no change in three, and progression in 13. Comparison of preangiogram levels with average levels between angiograms showed significant reduction in serum cholesterol, triglyceride, and blood pressure in the group with lesion improvement but not in the group with lesion progression. Sporadic examples of human atherosclerosis regression are known, but most other studies in man indicate only atherosclerosis progression. Our different result appears due to our selection of patients and radiographic method. We have studied patients with earlier atherosclerosis than previous workers, using a radiographic procedure more sensitive to small changes in lesions.", "contents": "Regression and progression of early femoral atherosclerosis in treated hyperlipoproteinemic patients. Femoral angiograms were done to evaluate change in early atherosclerosis in 12 patients with type IV hyperlipoproteinemia and 13 with type II hyperlipoproteinemia. The patients' average age was 48 years; only one had claudication. Elevated blood lipids and blood pressure were treated with drugs and diet. Repeat angiograms after an interval of 13 months showed regression of atherosclerosis in nine patients, no change in three, and progression in 13. Comparison of preangiogram levels with average levels between angiograms showed significant reduction in serum cholesterol, triglyceride, and blood pressure in the group with lesion improvement but not in the group with lesion progression. Sporadic examples of human atherosclerosis regression are known, but most other studies in man indicate only atherosclerosis progression. Our different result appears due to our selection of patients and radiographic method. We have studied patients with earlier atherosclerosis than previous workers, using a radiographic procedure more sensitive to small changes in lesions."}
{"id": "PMID:189659", "title": "Receptors for peptide hormones. New insights into the pathophysiology of disease states in man.", "content": "The first step in the action of polypeptide hormones and many neurotransmitters is binding to receptor sites on the plasma membrane of the cell. These receptors are usually complex, high molecular weight proteins. Using a variety of receptor preparations and radioactively labeled hormones, radioreceptor assays for several hormones have been developed. These have allowed for assay of hormones for which no immunoassay exists. Such assays have shown increased levels of NSILA-s (an insulin-like peptide) in patients with nonpancreatic tumors and hypoglycemia. In disease states, the number or affinity of hormone receptors may be altered, leading to hormone resistant states such as the insulin resistance of obesity. A major factor regulating receptor concentration is the hormone itself. Several hormones seem to accelerate inactivation of their own receptors. Antibodies to membrane receptors are produced in at least three diseases and cause hormone resistance or mimic states of hormone excess.", "contents": "Receptors for peptide hormones. New insights into the pathophysiology of disease states in man. The first step in the action of polypeptide hormones and many neurotransmitters is binding to receptor sites on the plasma membrane of the cell. These receptors are usually complex, high molecular weight proteins. Using a variety of receptor preparations and radioactively labeled hormones, radioreceptor assays for several hormones have been developed. These have allowed for assay of hormones for which no immunoassay exists. Such assays have shown increased levels of NSILA-s (an insulin-like peptide) in patients with nonpancreatic tumors and hypoglycemia. In disease states, the number or affinity of hormone receptors may be altered, leading to hormone resistant states such as the insulin resistance of obesity. A major factor regulating receptor concentration is the hormone itself. Several hormones seem to accelerate inactivation of their own receptors. Antibodies to membrane receptors are produced in at least three diseases and cause hormone resistance or mimic states of hormone excess."}
{"id": "PMID:189662", "title": "[Subacute excitation caused by probable herpetic encephalitis. Favorable effects of lithium].", "content": "Herpetic encephalitis in a 16 year old adolescent of average intelligence up to then and having had no psychiatric disorders. 3 years later, the subacte hypomanic excitation like behaviour disorder, distrubed alimentary and sexual behaviour rendered maintenance in the family environment and professional activity difficult; and this in spite of the absence of membory disorders, and the preservation of verbal and pragmatagnosic possibilities. Use of lithium led to the progressive sedation of the behaviour disorders and enabled return to work of the patient in a protected environment. This favorable action of lithium in a state of excitation of organic origin seems to be situated in the present stream of research which is attempting to enlarge the indications for it beyond manic depressive psychosis.", "contents": "[Subacute excitation caused by probable herpetic encephalitis. Favorable effects of lithium]. Herpetic encephalitis in a 16 year old adolescent of average intelligence up to then and having had no psychiatric disorders. 3 years later, the subacte hypomanic excitation like behaviour disorder, distrubed alimentary and sexual behaviour rendered maintenance in the family environment and professional activity difficult; and this in spite of the absence of membory disorders, and the preservation of verbal and pragmatagnosic possibilities. Use of lithium led to the progressive sedation of the behaviour disorders and enabled return to work of the patient in a protected environment. This favorable action of lithium in a state of excitation of organic origin seems to be situated in the present stream of research which is attempting to enlarge the indications for it beyond manic depressive psychosis."}
{"id": "PMID:189666", "title": "Regulation of calcium metabolism.", "content": "This paper reviews the regulation of calcium metabolism in man. The body's calcium economy is determined by the relationship between the intestinal absorption of calcium, the renal handling of calcium, and by the movements of calcium in and out of the skeleton. These processes are influenced by many factors, the most important of which are parathyroid hormone and the hormones derived from the renal metabolism of vitamin D, notably 1,24-dihydroxyvitamin D3. The role of endogenous calcitonin in man is still controversial, but there are several other hormones which have some influence on calcium metabolism, including thyroid hormone, growth hormone, and the adrenal and gonadal steroids. Clinical disorders of calcium metabolism and their treatment are discussed in terms of the disturbances in normal physiology they represent.", "contents": "Regulation of calcium metabolism. This paper reviews the regulation of calcium metabolism in man. The body's calcium economy is determined by the relationship between the intestinal absorption of calcium, the renal handling of calcium, and by the movements of calcium in and out of the skeleton. These processes are influenced by many factors, the most important of which are parathyroid hormone and the hormones derived from the renal metabolism of vitamin D, notably 1,24-dihydroxyvitamin D3. The role of endogenous calcitonin in man is still controversial, but there are several other hormones which have some influence on calcium metabolism, including thyroid hormone, growth hormone, and the adrenal and gonadal steroids. Clinical disorders of calcium metabolism and their treatment are discussed in terms of the disturbances in normal physiology they represent."}
{"id": "PMID:189664", "title": "Hemifacial spasm associated with benign parotid tumor.", "content": "A case of hemifacial spasm associated with a benign parotid tumor is reported. Excision of the tumor relieved the symptoms.", "contents": "Hemifacial spasm associated with benign parotid tumor. A case of hemifacial spasm associated with a benign parotid tumor is reported. Excision of the tumor relieved the symptoms."}
{"id": "PMID:189665", "title": "Posturally-evoked vomiting; Association with posterior fossa lesions.", "content": "Posturally-evoked vomiting (PEV) dissociated from vertigo was present in two patients with proven posterior fossa mass lesions. In both instances PEV was a major aspect of the patients' symptomatology before other findings clearly indicated the presence of an infratentorial mass lesion. A distinction is drawn between benign postural vertigo, which almost always indicates a benign disorder of the peripheral vestibular apparatus, and PEV which indicates a central lesion within the posterior fossa. A possible anatomic-physiologic basis is offered for PEV, based on the dissociation of the \"vestibular syndrome,\" in which PEV increases while vertigo and nystagmus diminish.", "contents": "Posturally-evoked vomiting; Association with posterior fossa lesions. Posturally-evoked vomiting (PEV) dissociated from vertigo was present in two patients with proven posterior fossa mass lesions. In both instances PEV was a major aspect of the patients' symptomatology before other findings clearly indicated the presence of an infratentorial mass lesion. A distinction is drawn between benign postural vertigo, which almost always indicates a benign disorder of the peripheral vestibular apparatus, and PEV which indicates a central lesion within the posterior fossa. A possible anatomic-physiologic basis is offered for PEV, based on the dissociation of the \"vestibular syndrome,\" in which PEV increases while vertigo and nystagmus diminish."}
{"id": "PMID:189670", "title": "Effects of drugs on platelet function.", "content": "Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.", "contents": "Effects of drugs on platelet function. Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic."}
{"id": "PMID:189675", "title": "[Infantile digital fibromatosis. Anatomo-clinical and ultrastructural study].", "content": "About one personal case, authors consider clinical, histological and ultrastructural aspects of the infantile digital fibromatosis. They insist on the caracteristic features of the large granular and fibrillar cytoplasmic inclusions observed in the proliferative fibroblasts, and on the different signs of the metabolic hyperactivity of these cells. Elastogenesis was very scarce within the swelling but showed no evidence of qualitative abnormality. The discussion provides no definitive clue as to the nature or origin of the inclusions.", "contents": "[Infantile digital fibromatosis. Anatomo-clinical and ultrastructural study]. About one personal case, authors consider clinical, histological and ultrastructural aspects of the infantile digital fibromatosis. They insist on the caracteristic features of the large granular and fibrillar cytoplasmic inclusions observed in the proliferative fibroblasts, and on the different signs of the metabolic hyperactivity of these cells. Elastogenesis was very scarce within the swelling but showed no evidence of qualitative abnormality. The discussion provides no definitive clue as to the nature or origin of the inclusions."}
{"id": "PMID:189671", "title": "[The use of synthetic beta-1-24 corticotropin as a GH stimulating factor (author's transl)].", "content": "The authors have carried out research into the GH stimulating action of 0.25 mg of synthetic beta-1-24 corticotropin (Synacthen) injected intravenously into 26 healthy normally developed children. The results obtained prove the limited and irregular action of ACTH.", "contents": "[The use of synthetic beta-1-24 corticotropin as a GH stimulating factor (author's transl)]. The authors have carried out research into the GH stimulating action of 0.25 mg of synthetic beta-1-24 corticotropin (Synacthen) injected intravenously into 26 healthy normally developed children. The results obtained prove the limited and irregular action of ACTH."}
{"id": "PMID:189676", "title": "[The biochemistry of psoriasis].", "content": "Numerous general metabolic systems are disturbed in association with psoriasis: the frequency of diabetes mellitus and of hyperuricaemia, lipid disturbances and a decrease in folates as a result of their excessive consumption by the skin. Cutaneous metabolism is also altered. Numerous compounds are formed in excess from glucose: amino acids, fatty acids and sterols, lactic acid--the formation of which persists in the corneal layer, ribose and ribulose--synthesised as a result of glucose-6-phosphate-dehydrogenase hyperactivity (role of the increased catabolism of dehydro-epi-androsterone) and uronic acids. The accumulation of glycogen is probably due to excessive synthesis and impaired breakdown. These abnormalities may exist to a lesser extent in healthy skin. In the corneal layer there are lipid vacuoles visible under the electron microscope. Lipogenesis is increased. The same may apply to lipolysis (blood NEFA are increased). Esterification of cholesterol is decreased. The utilisation of ATP by cell membranes is probably diminished (low ATP ase activity). The absence of formation of keratohyaline is due to persistence of the repression which normally prevents it in the mucus body. Renewal of collagen appears increased. The synthesis of DNA is increased in the lesions and neighbouring areas. It is possible that these various abnormalities are dependent upon modifications in the regulator systems of cyclic AMP and GMP, variations in which are however discussed.", "contents": "[The biochemistry of psoriasis]. Numerous general metabolic systems are disturbed in association with psoriasis: the frequency of diabetes mellitus and of hyperuricaemia, lipid disturbances and a decrease in folates as a result of their excessive consumption by the skin. Cutaneous metabolism is also altered. Numerous compounds are formed in excess from glucose: amino acids, fatty acids and sterols, lactic acid--the formation of which persists in the corneal layer, ribose and ribulose--synthesised as a result of glucose-6-phosphate-dehydrogenase hyperactivity (role of the increased catabolism of dehydro-epi-androsterone) and uronic acids. The accumulation of glycogen is probably due to excessive synthesis and impaired breakdown. These abnormalities may exist to a lesser extent in healthy skin. In the corneal layer there are lipid vacuoles visible under the electron microscope. Lipogenesis is increased. The same may apply to lipolysis (blood NEFA are increased). Esterification of cholesterol is decreased. The utilisation of ATP by cell membranes is probably diminished (low ATP ase activity). The absence of formation of keratohyaline is due to persistence of the repression which normally prevents it in the mucus body. Renewal of collagen appears increased. The synthesis of DNA is increased in the lesions and neighbouring areas. It is possible that these various abnormalities are dependent upon modifications in the regulator systems of cyclic AMP and GMP, variations in which are however discussed."}
{"id": "PMID:189672", "title": "[Pituitary modifications in a case of Schilder disease (author's transl)].", "content": "In a case of Schilder disease with a heavy atrophy of adrenal cortex the immunocytological analysis of anterior pituitary shows a generalized hypertrophy and a severe last of granulations of the beta cells which reacted very weakly to au anti-serum anti-ACTH 17-39. These modifications agree with biological titration proving an hypersecretion of ACTH and beta MSH.", "contents": "[Pituitary modifications in a case of Schilder disease (author's transl)]. In a case of Schilder disease with a heavy atrophy of adrenal cortex the immunocytological analysis of anterior pituitary shows a generalized hypertrophy and a severe last of granulations of the beta cells which reacted very weakly to au anti-serum anti-ACTH 17-39. These modifications agree with biological titration proving an hypersecretion of ACTH and beta MSH."}
{"id": "PMID:189673", "title": "[Dissociation of results obtained with an immunofluorescence technique by using anti-ACTH antibodies in three cases of pituitary \"chromophobe\" adenoma without hypercorticism; ultrastructural study (author's transl)].", "content": "Morphological studies of 3 pituitary \"chromophobe\" adenoma in patients without hypercorticism show positive immunofluorescenct cells with anti alpha, 17-39 ACTH antibody which are not revealed with anti beta, 1-24 ACTH antibody. These cells observed at the ultrastructural level contain secretory granules of 1,000 to 1,500 A in diameter. The existence in these cells of a substance having an immunological relationship with ACTH without biological activity is discussed.", "contents": "[Dissociation of results obtained with an immunofluorescence technique by using anti-ACTH antibodies in three cases of pituitary \"chromophobe\" adenoma without hypercorticism; ultrastructural study (author's transl)]. Morphological studies of 3 pituitary \"chromophobe\" adenoma in patients without hypercorticism show positive immunofluorescenct cells with anti alpha, 17-39 ACTH antibody which are not revealed with anti beta, 1-24 ACTH antibody. These cells observed at the ultrastructural level contain secretory granules of 1,000 to 1,500 A in diameter. The existence in these cells of a substance having an immunological relationship with ACTH without biological activity is discussed."}
{"id": "PMID:189674", "title": "[Synthetic A.C.T.H. test. (Results obtained on aldosterone and cortisol blood level) (author's transl)].", "content": "During the beta 1-24 corticotropin stimulation test, it appears the increase of Aldosterone Blood level is more important (170,91% +/- 35,89 (S. E.)) and more significant (alpha less than 0,001) than for cortisol (+/- 54,47% +/- 9,45 (S. E.) - alpha less than 0,10). The authors suggest aldosterone assays have to be done in order to obtain a better estimation on adrenal response to synthetic A.C.T.H.", "contents": "[Synthetic A.C.T.H. test. (Results obtained on aldosterone and cortisol blood level) (author's transl)]. During the beta 1-24 corticotropin stimulation test, it appears the increase of Aldosterone Blood level is more important (170,91% +/- 35,89 (S. E.)) and more significant (alpha less than 0,001) than for cortisol (+/- 54,47% +/- 9,45 (S. E.) - alpha less than 0,10). The authors suggest aldosterone assays have to be done in order to obtain a better estimation on adrenal response to synthetic A.C.T.H."}
{"id": "PMID:189683", "title": "Comparison of the binding properties of two 6 beta-amidinopenicillanic acid derivatives that differ in their physiological effects on Escherichia coli.", "content": "The 6-beta-amidinopenicillanic acid derivative, mecillinam, was highly specific in its action on the growth of Escherichia coli. Concentrations from the minimal inhibitory concentration (0.05 mug/ml) up to at least 200 mug/ml resulted in the conversion of E. coli rods into osmotically stable spherical cells without significantly inhibiting cell growth or causing cell lysis. A second amidinopenicillanic acid derivative [6-([4-morpholinylmethylene] amino) penicillanic acid] showed identical effects on cell growth at concentrations from its minimal inhibitory concentration (0.2 mug/ml) up to at least 5 mug/ml but, at higher concentrations, increasing amounts of lysis occurred. Neither of these compounds showed the immediate inhibition of cell division that is observed with typical beta-lactam antibiotics. We have compared the binding of these two amidinopenicillanic acids to the individual penicillin-binding proteins of E. coli. Both compounds showed a high specificity of binding to penicillin-binding protein 2 at low concentrations. At higher concentrations mecillinam still maintained its high specificity for protein 2 and very little binding of mecillinam to any of the other binding proteins was detected with concentrations up to 1 mg/ml. The morpholino compound, however, showed extensive binding to proteins 1 and 4, and slight binding to proteins 5 and 6 at high concentrations. The morpholino compound therefore combined both the physiological properties and the binding properties of mecillinam with some of those of typical penicillins and cephalosporins. Lysis probably occurs at high concentrations of morpholino compound because it binds to penicillin-binding protein 1, since this is believed to be the target with which beta-lactams interact to inhibit cell elongation.", "contents": "Comparison of the binding properties of two 6 beta-amidinopenicillanic acid derivatives that differ in their physiological effects on Escherichia coli. The 6-beta-amidinopenicillanic acid derivative, mecillinam, was highly specific in its action on the growth of Escherichia coli. Concentrations from the minimal inhibitory concentration (0.05 mug/ml) up to at least 200 mug/ml resulted in the conversion of E. coli rods into osmotically stable spherical cells without significantly inhibiting cell growth or causing cell lysis. A second amidinopenicillanic acid derivative [6-([4-morpholinylmethylene] amino) penicillanic acid] showed identical effects on cell growth at concentrations from its minimal inhibitory concentration (0.2 mug/ml) up to at least 5 mug/ml but, at higher concentrations, increasing amounts of lysis occurred. Neither of these compounds showed the immediate inhibition of cell division that is observed with typical beta-lactam antibiotics. We have compared the binding of these two amidinopenicillanic acids to the individual penicillin-binding proteins of E. coli. Both compounds showed a high specificity of binding to penicillin-binding protein 2 at low concentrations. At higher concentrations mecillinam still maintained its high specificity for protein 2 and very little binding of mecillinam to any of the other binding proteins was detected with concentrations up to 1 mg/ml. The morpholino compound, however, showed extensive binding to proteins 1 and 4, and slight binding to proteins 5 and 6 at high concentrations. The morpholino compound therefore combined both the physiological properties and the binding properties of mecillinam with some of those of typical penicillins and cephalosporins. Lysis probably occurs at high concentrations of morpholino compound because it binds to penicillin-binding protein 1, since this is believed to be the target with which beta-lactams interact to inhibit cell elongation."}
{"id": "PMID:189684", "title": "Inactivation of lipid-containing viruses by long-chain alcohols.", "content": "This report describes the inactivation of lipid-containing viruses by several long-chain alcohols. A striking peak in antiviral activity was found for saturated alcohols having chain lengths from 10 to 14 carbons. Viruses having different membrane structure showed different susceptibilities to alcohols having different chain lengths and structural features. Decanol, dodecanol, and tetradecanol readily inactivated herpes simplex virus and the enveloped bacterial virus phi6. The lipid-containing virus PM2 was susceptible to decanol and dodecanol but comparatively unsusceptible to tetradecanol. The branched-chain alcohol phytol, a naturally occurring component of chlorophyll, was active against phi6 and herpes simplex virus but not against PM2. Polyoma virus and the bacteriophage phi23-1-a, which do not contain lipids, were not susceptible to inactivation by any of the alcohols tested. Experiments were also carried out to determine the effects of these compounds on cells. At 0.5 mM, decanol lysed human embryonic lung cells, erythrocytes, and the bacterial hosts for phi6 and PM2. Dodecanol, tetradecanol, and phytol at this concentration were less damaging to cells. At 0.05 mM, none of the alcohols caused observable cytopathic effects on human embryonic lung cells, although several of the alcohols at this concentration were active against herpes simplex virus. Our findings suggest that dodecanol, tetradecanol, and phytol may warrant further studies as potential antiviral agents, particularly for topical application to virus-infected areas of the skin.", "contents": "Inactivation of lipid-containing viruses by long-chain alcohols. This report describes the inactivation of lipid-containing viruses by several long-chain alcohols. A striking peak in antiviral activity was found for saturated alcohols having chain lengths from 10 to 14 carbons. Viruses having different membrane structure showed different susceptibilities to alcohols having different chain lengths and structural features. Decanol, dodecanol, and tetradecanol readily inactivated herpes simplex virus and the enveloped bacterial virus phi6. The lipid-containing virus PM2 was susceptible to decanol and dodecanol but comparatively unsusceptible to tetradecanol. The branched-chain alcohol phytol, a naturally occurring component of chlorophyll, was active against phi6 and herpes simplex virus but not against PM2. Polyoma virus and the bacteriophage phi23-1-a, which do not contain lipids, were not susceptible to inactivation by any of the alcohols tested. Experiments were also carried out to determine the effects of these compounds on cells. At 0.5 mM, decanol lysed human embryonic lung cells, erythrocytes, and the bacterial hosts for phi6 and PM2. Dodecanol, tetradecanol, and phytol at this concentration were less damaging to cells. At 0.05 mM, none of the alcohols caused observable cytopathic effects on human embryonic lung cells, although several of the alcohols at this concentration were active against herpes simplex virus. Our findings suggest that dodecanol, tetradecanol, and phytol may warrant further studies as potential antiviral agents, particularly for topical application to virus-infected areas of the skin."}
{"id": "PMID:189685", "title": "Persistence of poliovirus 1 in soil and on vegetables grown in soil previously flooded with inoculated sewage sludge or effluent.", "content": "Land disposal of sewage sludge and effluent is becoming a common practice in the United States. The fertilizer content and humus value of such wastes are useful for agricultural purposes, and the recycling of sewage onto the land eliminates many of our stream pollution problems. The potential exists for crops grown in such irrigated soil to be contaminated by viruses that may be present in the sewage. Studies were initiated to determine viral persistence in soil and on crops grown under natural conditions in field plots that had been flooded to a depth of 1 inch (2.54 cm) with poliovirus 1-inoculated sewage wastes. Lettuce and radishes were planted in sludge- or effluent-flooded soil. In one study, the vegetables were planted 1 day before flooding, and in another they were planted 3 days after the plots were flooded. Survival of poliovirus 1 in soil irrigated with inoculated sewage sludge and effluent was determined during two summer growing seasons and one winter period. The longest period of survival was during the winter, when virus was detected after 96 days. During the summer, the longest survival period was 11 days. Poliovirus 1 was recovered from the mature vegetables 23 days after flooding of the plots had ceased. Lettuce and radishes are usually harvested 3 to 4 weeks after planting.", "contents": "Persistence of poliovirus 1 in soil and on vegetables grown in soil previously flooded with inoculated sewage sludge or effluent. Land disposal of sewage sludge and effluent is becoming a common practice in the United States. The fertilizer content and humus value of such wastes are useful for agricultural purposes, and the recycling of sewage onto the land eliminates many of our stream pollution problems. The potential exists for crops grown in such irrigated soil to be contaminated by viruses that may be present in the sewage. Studies were initiated to determine viral persistence in soil and on crops grown under natural conditions in field plots that had been flooded to a depth of 1 inch (2.54 cm) with poliovirus 1-inoculated sewage wastes. Lettuce and radishes were planted in sludge- or effluent-flooded soil. In one study, the vegetables were planted 1 day before flooding, and in another they were planted 3 days after the plots were flooded. Survival of poliovirus 1 in soil irrigated with inoculated sewage sludge and effluent was determined during two summer growing seasons and one winter period. The longest period of survival was during the winter, when virus was detected after 96 days. During the summer, the longest survival period was 11 days. Poliovirus 1 was recovered from the mature vegetables 23 days after flooding of the plots had ceased. Lettuce and radishes are usually harvested 3 to 4 weeks after planting."}
{"id": "PMID:189686", "title": "Poliovirus aggregates and their survival in water.", "content": "Inactivation of aggregated poliovirus by bromine is characterized by a continuously decreasing reaction rate. Poliovirus released from infected cells in these experiments by alternate freezing and thawing in water without electrolytes has always been aggregated. The aggregates persist even on 7,000-fold dilution in ion-free water. Virus similarly released into phosphate-buffered saline solution may be well dispersed, but it aggregates when sedimented into a salt-free sucrose gradient or when it is diluted as little as 10-fold in water. Large one-step dilutions of dispersed virus in water remain dispersed. Aggregated virus was not dispersed by one-step dilution (7,000-fold) in distilled or untreated lake water but was dispersed if phosphate-buffered saline or clarified secondary sewage plant effluent was used as diluent. Dispersed virus aggregates at all dilutions in alum-treated, finished water from the city filter plant. This may be the result of complex formation with insoluble material rather than virion-virion aggregation. A simple procedure is described for rendering a very dilute suspension of mixed virion aggregates into a three-part spectrum of sizes.", "contents": "Poliovirus aggregates and their survival in water. Inactivation of aggregated poliovirus by bromine is characterized by a continuously decreasing reaction rate. Poliovirus released from infected cells in these experiments by alternate freezing and thawing in water without electrolytes has always been aggregated. The aggregates persist even on 7,000-fold dilution in ion-free water. Virus similarly released into phosphate-buffered saline solution may be well dispersed, but it aggregates when sedimented into a salt-free sucrose gradient or when it is diluted as little as 10-fold in water. Large one-step dilutions of dispersed virus in water remain dispersed. Aggregated virus was not dispersed by one-step dilution (7,000-fold) in distilled or untreated lake water but was dispersed if phosphate-buffered saline or clarified secondary sewage plant effluent was used as diluent. Dispersed virus aggregates at all dilutions in alum-treated, finished water from the city filter plant. This may be the result of complex formation with insoluble material rather than virion-virion aggregation. A simple procedure is described for rendering a very dilute suspension of mixed virion aggregates into a three-part spectrum of sizes."}
{"id": "PMID:189702", "title": "Rotavirus infections in a maternity unit.", "content": "Between May and August 1975, rotaviruses were detected in the stools of 76 out of 174 (44%) newborn babies in the maternity unit at this hospital. Infection occurred less frequently in breast-fed than in bottle-fed babies (P less than 0.001). However, only 7 out of 76 (8%) babies who excreted rotaviruses had symptoms and these were mild. Complement fixation tests did not show any apparent difference in the antibody titres or serological responses between mothers of rotavirus positive or negative babies. When 68 faecal extracts known to contain rotaviruses by electron microscopy were inoculated by centrifugation on to monolayers of continuous pig kidney cell cultures (IB-RS-2), rotavirus antigen was detected by immunofluorescence in 65 (95.5%) specimens, 58 being positive after centrifugation at 3000 g and a further 7 after centrifugation at 10 000 g. Antigen was first detected 6 hours after inoculation of specimens, maximum levels being detected at 24 hours.", "contents": "Rotavirus infections in a maternity unit. Between May and August 1975, rotaviruses were detected in the stools of 76 out of 174 (44%) newborn babies in the maternity unit at this hospital. Infection occurred less frequently in breast-fed than in bottle-fed babies (P less than 0.001). However, only 7 out of 76 (8%) babies who excreted rotaviruses had symptoms and these were mild. Complement fixation tests did not show any apparent difference in the antibody titres or serological responses between mothers of rotavirus positive or negative babies. When 68 faecal extracts known to contain rotaviruses by electron microscopy were inoculated by centrifugation on to monolayers of continuous pig kidney cell cultures (IB-RS-2), rotavirus antigen was detected by immunofluorescence in 65 (95.5%) specimens, 58 being positive after centrifugation at 3000 g and a further 7 after centrifugation at 10 000 g. Antigen was first detected 6 hours after inoculation of specimens, maximum levels being detected at 24 hours."}
{"id": "PMID:189703", "title": "Effects of ozone and sulfur dioxide on virus growth in mice.", "content": "Inhalation of ozone and sulfur dioxide inhibited influenza virus growth in the nose of mice. Ozone inhalation caused the more pronounced inhibition of influenza virus growth: 0.6 ppm ozone for 3 hours post-virus exposure almost completely inhibited influenza virus growth in the nose, whereas sulfur dioxide (6 ppm for 7 days) causes only partial inhibition of influenza growth in the nose. Neither gas altered the propagation of influenza virus in the lungs of mice. Vesicular stomatitis virus (VSV) growth was either unaffected by exposure to ozone (0.9 ppm for 3 hours) or, when ozone exposure preceeded VSV exposure, the virus may have grown to slightly higher titer. The inhibitory effect of ozone and sulfur dioxide on influenza virus growth in nasal epithelium suggests a competitive interaction between the chemical inhalant, the virus, and host tissues, with net consequences for the pathogenesis of this disease. If the effcts of these inhalants are to be properly interpreted, they should be determined for all major regions of virus growth and inhalant deposition.", "contents": "Effects of ozone and sulfur dioxide on virus growth in mice. Inhalation of ozone and sulfur dioxide inhibited influenza virus growth in the nose of mice. Ozone inhalation caused the more pronounced inhibition of influenza virus growth: 0.6 ppm ozone for 3 hours post-virus exposure almost completely inhibited influenza virus growth in the nose, whereas sulfur dioxide (6 ppm for 7 days) causes only partial inhibition of influenza growth in the nose. Neither gas altered the propagation of influenza virus in the lungs of mice. Vesicular stomatitis virus (VSV) growth was either unaffected by exposure to ozone (0.9 ppm for 3 hours) or, when ozone exposure preceeded VSV exposure, the virus may have grown to slightly higher titer. The inhibitory effect of ozone and sulfur dioxide on influenza virus growth in nasal epithelium suggests a competitive interaction between the chemical inhalant, the virus, and host tissues, with net consequences for the pathogenesis of this disease. If the effcts of these inhalants are to be properly interpreted, they should be determined for all major regions of virus growth and inhalant deposition."}
{"id": "PMID:189707", "title": "Carcinoma of the anus.", "content": "Carcinoma of the anus represents about 2% of cancers of the large bowel. From 1950 to 1970, 20 patients were treated for this condition. Included were 113 patients with squamous cell carcinoma (31 perianal), 64 with basalid squamous carcinoma, 8 with Paget's disease of the anus, 7 with melanoma, 6 with basal cell carcinoma, and 6 with adenocarcinoma. Combined abdomino-perineal resection was the treatment of choice except for perianal lesions; for these, local excision was used most frequently. Inguinal node dissection was used infrequently, and it is not possible to draw meaningful conclusions from the data. Overall survival rates for patients having anal squamous cell carcinoma are similar except when lymphatic invasion is present; then basaloid lesions have a significantly better prognosis. For rare anal carcinomas, histopathologic findings dictate the end results-- the better the findings and more satisfactory the results.", "contents": "Carcinoma of the anus. Carcinoma of the anus represents about 2% of cancers of the large bowel. From 1950 to 1970, 20 patients were treated for this condition. Included were 113 patients with squamous cell carcinoma (31 perianal), 64 with basalid squamous carcinoma, 8 with Paget's disease of the anus, 7 with melanoma, 6 with basal cell carcinoma, and 6 with adenocarcinoma. Combined abdomino-perineal resection was the treatment of choice except for perianal lesions; for these, local excision was used most frequently. Inguinal node dissection was used infrequently, and it is not possible to draw meaningful conclusions from the data. Overall survival rates for patients having anal squamous cell carcinoma are similar except when lymphatic invasion is present; then basaloid lesions have a significantly better prognosis. For rare anal carcinomas, histopathologic findings dictate the end results-- the better the findings and more satisfactory the results."}
{"id": "PMID:189708", "title": "Prostaglandins E and F in endocrine diarrheagenic syndromes.", "content": "The role of prostaglandins in endocrine diarrheagenic syndromes was evaluated by measuring peripheral concentration of immunoreactive PGE and PGF in patients with non-endocrine diarrhea as well as those with the Zollinger-Ellison (Z-E) syndrome, MCT, carcinoid tumors and the WDHA syndrome. In 21 normals, PGE and PGF levels averaged 272 +/- 18 and 119 +/- 14 pg/ml, respectively. Twenty eight patients with diarrhea of non-endocrine origin (mainly inflammatory bowel disease) had levels indistinguishable from normal, i.e. 353 +/- 25 and 77 +/- 37 pg/ml, respectively. Among 29 patients with the Zollinger-Ellison syndrome (mean gastrin 6127 +/- 3267 pg/ml) only 2 had significantly elevated PGE levels; mean PGE levels, 382 +/- 32 pg/ml, were not significantly different from normal and did not correlate with either diarrhea or the serum gastrin concentration. In contrast, 18 of 22 patients with carcinoid tumors (mean blood serotonin concentration 1655 +/- 604 ng/ml; mean urinary excretion of 5 HIAA 66.8 +/- 16.7 mg/day) had elevated peripheral concentrations of PGE. The mean PGE level (1367 +/- 245 pg/ml) was significantly elevated (P less than 0.001). Nonetheless PGE levels did not correlate with diarrhea, blood concentrations of serotonin, or urinary indole excretion. MCT (mean serum calcitonin 24.5 +/- 6.3 ng/ml) was similarly associated with consistent (18/19) elevation in peripheral concentrations of PGE (mean 1922 +/- 541 pg/ml; P less than 0.001). Inthis syndrome, PGE levels were higher in patients with diarrhea and in those with markedly elevated serum thyrocalcitonin levels. Finally, 8 of 21 patients with the WDHA syndrome had increased levels of PGE. Although 13 of 17 patients had high levels of VIP (mean 8133 pg/ml), 2 patients had hyperprostaglandinemia in the face of normal peripheral concentrations of VIP. In one patient the serum PGE level was elevated prior to resection of the primary pancreatic neoplasm (9939 pg/ml) as well as the subsequent extirpation of a solitary hepatic metastasis (1063 pg/ml); following each procedure the diarrhea abated and the PGE level returned to normal. In none of these syndromes were mean PGF levels elevated. The study has documented hyperprostaglandinemia in some endocrine diarrheagenic syndromes and validated the usefullness of measurements of PGE in patients with unexplained diarrhea.", "contents": "Prostaglandins E and F in endocrine diarrheagenic syndromes. The role of prostaglandins in endocrine diarrheagenic syndromes was evaluated by measuring peripheral concentration of immunoreactive PGE and PGF in patients with non-endocrine diarrhea as well as those with the Zollinger-Ellison (Z-E) syndrome, MCT, carcinoid tumors and the WDHA syndrome. In 21 normals, PGE and PGF levels averaged 272 +/- 18 and 119 +/- 14 pg/ml, respectively. Twenty eight patients with diarrhea of non-endocrine origin (mainly inflammatory bowel disease) had levels indistinguishable from normal, i.e. 353 +/- 25 and 77 +/- 37 pg/ml, respectively. Among 29 patients with the Zollinger-Ellison syndrome (mean gastrin 6127 +/- 3267 pg/ml) only 2 had significantly elevated PGE levels; mean PGE levels, 382 +/- 32 pg/ml, were not significantly different from normal and did not correlate with either diarrhea or the serum gastrin concentration. In contrast, 18 of 22 patients with carcinoid tumors (mean blood serotonin concentration 1655 +/- 604 ng/ml; mean urinary excretion of 5 HIAA 66.8 +/- 16.7 mg/day) had elevated peripheral concentrations of PGE. The mean PGE level (1367 +/- 245 pg/ml) was significantly elevated (P less than 0.001). Nonetheless PGE levels did not correlate with diarrhea, blood concentrations of serotonin, or urinary indole excretion. MCT (mean serum calcitonin 24.5 +/- 6.3 ng/ml) was similarly associated with consistent (18/19) elevation in peripheral concentrations of PGE (mean 1922 +/- 541 pg/ml; P less than 0.001). Inthis syndrome, PGE levels were higher in patients with diarrhea and in those with markedly elevated serum thyrocalcitonin levels. Finally, 8 of 21 patients with the WDHA syndrome had increased levels of PGE. Although 13 of 17 patients had high levels of VIP (mean 8133 pg/ml), 2 patients had hyperprostaglandinemia in the face of normal peripheral concentrations of VIP. In one patient the serum PGE level was elevated prior to resection of the primary pancreatic neoplasm (9939 pg/ml) as well as the subsequent extirpation of a solitary hepatic metastasis (1063 pg/ml); following each procedure the diarrhea abated and the PGE level returned to normal. In none of these syndromes were mean PGF levels elevated. The study has documented hyperprostaglandinemia in some endocrine diarrheagenic syndromes and validated the usefullness of measurements of PGE in patients with unexplained diarrhea."}
{"id": "PMID:189709", "title": "Observations on the postoperative tumor growth behavior of certain islet cell tumors.", "content": "Over a period of 21 years 39 patients with gastrinoma were surgically treated. Thirty-three patients had total gastrectomy with two postoperative deaths, and 6 patients had a lesser procedure. The postoperative fasting gastrin levels remained elevated and did not always indicate the extent of tumor involvement. Further mobilization of tumor gastrin by provocative infusion of calcium gluceptate, 15 mg/kg of body weight, should be carried out routinely. A hepatic angiogram should be considered when the gastrin levels exceed 1,000 picograms per ml. Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma. All patients felt better and gained from three to 35 pounds in weight. Since 60% of the patients died or have definite evidence of tumor activity it is assumed that the tumor growth was not inhibited and that it is malignant. Approximately 40% of the patients seem to do well despite modest elevations in gastrin levels suggesting that the retained tumor could be considered benign.", "contents": "Observations on the postoperative tumor growth behavior of certain islet cell tumors. Over a period of 21 years 39 patients with gastrinoma were surgically treated. Thirty-three patients had total gastrectomy with two postoperative deaths, and 6 patients had a lesser procedure. The postoperative fasting gastrin levels remained elevated and did not always indicate the extent of tumor involvement. Further mobilization of tumor gastrin by provocative infusion of calcium gluceptate, 15 mg/kg of body weight, should be carried out routinely. A hepatic angiogram should be considered when the gastrin levels exceed 1,000 picograms per ml. Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma. All patients felt better and gained from three to 35 pounds in weight. Since 60% of the patients died or have definite evidence of tumor activity it is assumed that the tumor growth was not inhibited and that it is malignant. Approximately 40% of the patients seem to do well despite modest elevations in gastrin levels suggesting that the retained tumor could be considered benign."}
{"id": "PMID:189710", "title": "Congenital mixed vascular deformities of the lower limb: the relevance of lymphatic abnormalities to their diagnosis and treatment.", "content": "Nineteen patients with vascular deformities of the lower extremity were studied and were classified into three groups based on their clinical and angiographic findings. 1) The Klippel or Venous Dysplasia Group (n = 8) demonstrated: cutaneous nevi of metameric distribution, congenital varices (many of which were anomalous by phlebography), hypertrophy of bone and other tissues, but no evidence of arterial involvement by arteriography. 2) Congenital Arterio-Venous Fistulae Group (n = 7) showed: cutaneous angiomata, hypertrophy of bone and soft tissues, but arteriographic findings of single or multiple arterio-venous fistulae. 3) Scattered Angiomata Group (n = 4) had single or multiple angiomata involving the lower limb in particular. Arteriography was normal, while phlbography revealed venous abnormalities. Lymphography was performed on all patients. Six of 8 of the Klippel group demonstrated aplastic or hypoplastic lymphatics by lymphography. By contrast, all 7 of the patients in the Congenital Arterio-Venous Fistulae Group showed in their lymphographic findings-three of 4 of these patients had aplasia or hypoplasia. Fourteen of the 19 patients complained of painful swelling as a major symptom. Lymphatic fistulae and lymphoceles developed in several patients.Four patients underwent reduction operations for lymphedema. Lymphatic abnormalities as demonstrated by lymphography play a significant role in mixed vascular deformities of the lower extremities.", "contents": "Congenital mixed vascular deformities of the lower limb: the relevance of lymphatic abnormalities to their diagnosis and treatment. Nineteen patients with vascular deformities of the lower extremity were studied and were classified into three groups based on their clinical and angiographic findings. 1) The Klippel or Venous Dysplasia Group (n = 8) demonstrated: cutaneous nevi of metameric distribution, congenital varices (many of which were anomalous by phlebography), hypertrophy of bone and other tissues, but no evidence of arterial involvement by arteriography. 2) Congenital Arterio-Venous Fistulae Group (n = 7) showed: cutaneous angiomata, hypertrophy of bone and soft tissues, but arteriographic findings of single or multiple arterio-venous fistulae. 3) Scattered Angiomata Group (n = 4) had single or multiple angiomata involving the lower limb in particular. Arteriography was normal, while phlbography revealed venous abnormalities. Lymphography was performed on all patients. Six of 8 of the Klippel group demonstrated aplastic or hypoplastic lymphatics by lymphography. By contrast, all 7 of the patients in the Congenital Arterio-Venous Fistulae Group showed in their lymphographic findings-three of 4 of these patients had aplasia or hypoplasia. Fourteen of the 19 patients complained of painful swelling as a major symptom. Lymphatic fistulae and lymphoceles developed in several patients.Four patients underwent reduction operations for lymphedema. Lymphatic abnormalities as demonstrated by lymphography play a significant role in mixed vascular deformities of the lower extremities."}
{"id": "PMID:189711", "title": "The mechanism of action of dicyclomine hydrochloride on rabbit detrusor muscle and vas deferens.", "content": "Dicyclomine inhibited responses of rabbit detrusor muscle to transmural stimulation more than atropine or lidocaine, and also inhibited responses to acetylcholine and to KCl. Responses of rabbit vas deferens to noradrenaline and transmural stimulation were inhibited by dicyclomine. Dicyclomine was as potent a local anesthetic as lidocaine, as determined by the guinea-pig wheal test. 45Ca++ exchange in the rabbit detrusor, measured by the lanthanum methods, was not altered by atropine, lidocaine or dicyclomine. It is concluded that dicyclomine not only acts as an anticholinergic agent but also impairs excitation-contraction coupling and release of transmitter from autonomic nerves.", "contents": "The mechanism of action of dicyclomine hydrochloride on rabbit detrusor muscle and vas deferens. Dicyclomine inhibited responses of rabbit detrusor muscle to transmural stimulation more than atropine or lidocaine, and also inhibited responses to acetylcholine and to KCl. Responses of rabbit vas deferens to noradrenaline and transmural stimulation were inhibited by dicyclomine. Dicyclomine was as potent a local anesthetic as lidocaine, as determined by the guinea-pig wheal test. 45Ca++ exchange in the rabbit detrusor, measured by the lanthanum methods, was not altered by atropine, lidocaine or dicyclomine. It is concluded that dicyclomine not only acts as an anticholinergic agent but also impairs excitation-contraction coupling and release of transmitter from autonomic nerves."}
{"id": "PMID:189712", "title": "Motor disturbances produced by intrastriatal injection of cyclic AMP and cyclic GMP.", "content": "Male albino rats were permanently cannulated bilaterally in the caudate/putamen nucleus and subsequently injected unilaterally with cyclic AMP or cyclic GMP. Both of these cyclic nucleotides failed to produce any obvious change in motor activity. The concomitant intrastriatal injection of carbachol and cyclic AMP resulted in enhancement of the carbachol-induced dyskinesias. Under similar conditions, cyclic GMP blocked the carbachol effects. The dibutyryl (db) derivatives of cyclic AMP and cyclic GMP both enhanced the carbachol-induced dyskinesias and both db cyclic nucleotides induced dyskinesias when injected intrastriatally alone. The concomitant intrastriatal injection of dopamine and carbachol resulted in a blockade of the carbachol-induced dyskinesias. Dopmaine had no effect on db cyclic AMP and db cyclic GMP dyskinesias. The db cyclic AMP effects characteristically involved the distal limb musculature, while the db cycle GMP effects largely involved the proximal limb and trunk muscles. The hypothesis for opposing action of cyclic AMP and cyclic GMP in the CNS and the discrepancy between the effects of intrastriatal injection of cyclic AMP and dopamine were discussed.", "contents": "Motor disturbances produced by intrastriatal injection of cyclic AMP and cyclic GMP. Male albino rats were permanently cannulated bilaterally in the caudate/putamen nucleus and subsequently injected unilaterally with cyclic AMP or cyclic GMP. Both of these cyclic nucleotides failed to produce any obvious change in motor activity. The concomitant intrastriatal injection of carbachol and cyclic AMP resulted in enhancement of the carbachol-induced dyskinesias. Under similar conditions, cyclic GMP blocked the carbachol effects. The dibutyryl (db) derivatives of cyclic AMP and cyclic GMP both enhanced the carbachol-induced dyskinesias and both db cyclic nucleotides induced dyskinesias when injected intrastriatally alone. The concomitant intrastriatal injection of dopamine and carbachol resulted in a blockade of the carbachol-induced dyskinesias. Dopmaine had no effect on db cyclic AMP and db cyclic GMP dyskinesias. The db cyclic AMP effects characteristically involved the distal limb musculature, while the db cycle GMP effects largely involved the proximal limb and trunk muscles. The hypothesis for opposing action of cyclic AMP and cyclic GMP in the CNS and the discrepancy between the effects of intrastriatal injection of cyclic AMP and dopamine were discussed."}
{"id": "PMID:189714", "title": "EEG of striate cortex in blind monkeys: effects of eye movements and sleep.", "content": "After control studies, using electrodes permanently implanted in the central visual system, squirrel monkeys and macaques were in most instances blinded by acute glaucoma. This permitted subsequent observation of eye movements. Ocular nystagmus developed in all cases. Beginning immediately upon recovery from anesthesia, and persisting for at least 1 year, the EEG of the striate cortex was characterized by totally flat periods up to several seconds in duration which were ended abruptly by a sharp \"spike\" trailed in turn by a ragged high voltage, slow pattern for another second or two. The great majority of these \"spikes\" from the blind striate cortex occurred within 60-200 msec after a saccadic eye movement, made either in nystagmus or attempted fixation. They were not dependent upon proprioception from the extraocular muscles. It is suggested that they represent a \"corollary discharge\" for movement of the eyes. The blind striate cortex was judged to be hyperexcitable on the basis of these saccade-associated \"spikes\", not often observable in intact monkeys, and from the increase both in response evoked by electrical stimulation of optic radiation and amplitude of the EEG in sleep.", "contents": "EEG of striate cortex in blind monkeys: effects of eye movements and sleep. After control studies, using electrodes permanently implanted in the central visual system, squirrel monkeys and macaques were in most instances blinded by acute glaucoma. This permitted subsequent observation of eye movements. Ocular nystagmus developed in all cases. Beginning immediately upon recovery from anesthesia, and persisting for at least 1 year, the EEG of the striate cortex was characterized by totally flat periods up to several seconds in duration which were ended abruptly by a sharp \"spike\" trailed in turn by a ragged high voltage, slow pattern for another second or two. The great majority of these \"spikes\" from the blind striate cortex occurred within 60-200 msec after a saccadic eye movement, made either in nystagmus or attempted fixation. They were not dependent upon proprioception from the extraocular muscles. It is suggested that they represent a \"corollary discharge\" for movement of the eyes. The blind striate cortex was judged to be hyperexcitable on the basis of these saccade-associated \"spikes\", not often observable in intact monkeys, and from the increase both in response evoked by electrical stimulation of optic radiation and amplitude of the EEG in sleep."}
{"id": "PMID:189715", "title": "Electrophysiological analysis of the circuitry and of the corticonuclear relationships in the agranular cerebellum of irradiated rats.", "content": "The cerebellar circuitry and the corticonuclear relationships were studied in the cerebellum of adult rats rendered agranular through 7 successive exposures to X-ray radiations during infancy. Data were obtained through examination of electrical responses induced in Purkinje cells (PC) and in neurons of the lateral vestibular nucleus (LVN) by cerebellar and spinal stimulations. In irradiated rats, PC exhibited antidromic activation with a high axonal threshold and 70% of them also presented typical climbing fiber responses (CFRs). By contrast, they exceptionnally exhibited responses via the mossy fiber (MF)-granule cell pathway, but two other classes of responses were identified: i) short latency single spike responses attributed to a direct excitatory impingement of MF onto PC; ii) atypical CFRs formed of high frequency bursts of simple spikes which were seen in 76% of PC tested. Furthermore, 53% of these cells also presented typical CFRs, strongly suggesting these PC were innervated by more than one CF, thus confirming previous data on the same type of agranular cerebellum. In the LVN neurons of control and irradiated rats, spinal and cerebellar stimulations evoked clear cut IPSPs. On the basis of their shape, latency, and occurrence in animals with or without cerebellum and with or without lesion of the CF pathway, they were interpreted as mediated through direct or synaptic activation of PC or through an extracerebellar pathway. In irradiated rats, the quantitative study of these IPSPs gave further arguments in favor of a multiinnervation of PC by CF and of an important reafferentation of MF onto PC. However, the functional efficiency of this reafferentation appeared very low, as tested by activation of MF originating in the spinal cord. Finally, the intracellular recording of LVN neurons showed that a large majority of PC axons retained normal synaptic connections with nuclear cells in treated animals, indicating that corticonuclear relationships do not markedly depend upon granule cells and normal CF input.", "contents": "Electrophysiological analysis of the circuitry and of the corticonuclear relationships in the agranular cerebellum of irradiated rats. The cerebellar circuitry and the corticonuclear relationships were studied in the cerebellum of adult rats rendered agranular through 7 successive exposures to X-ray radiations during infancy. Data were obtained through examination of electrical responses induced in Purkinje cells (PC) and in neurons of the lateral vestibular nucleus (LVN) by cerebellar and spinal stimulations. In irradiated rats, PC exhibited antidromic activation with a high axonal threshold and 70% of them also presented typical climbing fiber responses (CFRs). By contrast, they exceptionnally exhibited responses via the mossy fiber (MF)-granule cell pathway, but two other classes of responses were identified: i) short latency single spike responses attributed to a direct excitatory impingement of MF onto PC; ii) atypical CFRs formed of high frequency bursts of simple spikes which were seen in 76% of PC tested. Furthermore, 53% of these cells also presented typical CFRs, strongly suggesting these PC were innervated by more than one CF, thus confirming previous data on the same type of agranular cerebellum. In the LVN neurons of control and irradiated rats, spinal and cerebellar stimulations evoked clear cut IPSPs. On the basis of their shape, latency, and occurrence in animals with or without cerebellum and with or without lesion of the CF pathway, they were interpreted as mediated through direct or synaptic activation of PC or through an extracerebellar pathway. In irradiated rats, the quantitative study of these IPSPs gave further arguments in favor of a multiinnervation of PC by CF and of an important reafferentation of MF onto PC. However, the functional efficiency of this reafferentation appeared very low, as tested by activation of MF originating in the spinal cord. Finally, the intracellular recording of LVN neurons showed that a large majority of PC axons retained normal synaptic connections with nuclear cells in treated animals, indicating that corticonuclear relationships do not markedly depend upon granule cells and normal CF input."}
{"id": "PMID:189716", "title": "Myocardial scintigraphy with technetium 99m pyrophosphate.", "content": "The pyrophosphate of Tc99m attaches itself to ischaemic myocardial cells, and therefore makes it possible to obtain a scintigram of necrotic or necrosing myocardium. In a series of 65 cases the scintigram was positive in every case in which there had been a recent transmural infarct (17 cases). The results showed greater variation in the other ischaemic conditions involving the myocardium (limited infarcts or simple angina). The progress as a function of time was stuided in a series of fairly recent and older infarcts. The limitations and future prospects of this investigations are discussed.", "contents": "Myocardial scintigraphy with technetium 99m pyrophosphate. The pyrophosphate of Tc99m attaches itself to ischaemic myocardial cells, and therefore makes it possible to obtain a scintigram of necrotic or necrosing myocardium. In a series of 65 cases the scintigram was positive in every case in which there had been a recent transmural infarct (17 cases). The results showed greater variation in the other ischaemic conditions involving the myocardium (limited infarcts or simple angina). The progress as a function of time was stuided in a series of fairly recent and older infarcts. The limitations and future prospects of this investigations are discussed."}
{"id": "PMID:189717", "title": "Comparative effect of methioninyl adenylate on the growth of Salmonella typhimurium and Pseudomonas aeruginosa.", "content": "The bacteriostatic effect of methioninyl adenylate(MAMP)--a specific inhibitor of the enzyme methionyl-tRNA synthetase--was investigated on Salmonella typhimurium and Pseudomonas aeruginosa. 0.1 mM of this molecule added to the culture, inhibits the growth of S. typhimurium. The inhibition is specifically reversible by 0.1 mM L-methionine. In the same conditions even 1-2 mM MAMP has a very slight effect on the growth rate of P. aeruginosa and only during the first two generations. The same observation was made with the two other members of the fluorescens group P.fluorescens and P.putida. The growth rate of P. testosteroni with 1 mM MAMP in the medium is similar to the growth rate of P. aeruginosa but the other member of the acidovorans group P. acidovorans is much more affected by the smae concentration of the inhibitor. --P. multivorans is inhibited by MAMP like P. acidovorans but with a somewhat higher yield at the end of the culture. --MAMP has no effect on P. alcaligenes. The possible reasons for the weak bacteriostatic effect of MAMP on P. aeruginosa were investigated. It was established that the inhibitor enters the cells and is not used as a carbon and energy source. The intracellular methionine concentration in S. typhimurium and in P. aeruginosa is about the same and does not increase when bacteria are cultivated with MAMP. The MTS of the two microorganisms is inhibited by MAMP in vitro to about the same extent. Furthermore the tRNAmet from P. aeruginosa are fully acylated after 3 to 4 generations with this compound. Nevertheless MAMP elicits higher MTS activity in P. aeruginosa and in P. acidovorans after 1 h of incubation. The most striking difference between S. typhimurium and P. aeruginosa is that the intra and extracellular level of 5'phosphodiesterase which degrades MAMP is 10-20 fold higher in the second than in the first species.", "contents": "Comparative effect of methioninyl adenylate on the growth of Salmonella typhimurium and Pseudomonas aeruginosa. The bacteriostatic effect of methioninyl adenylate(MAMP)--a specific inhibitor of the enzyme methionyl-tRNA synthetase--was investigated on Salmonella typhimurium and Pseudomonas aeruginosa. 0.1 mM of this molecule added to the culture, inhibits the growth of S. typhimurium. The inhibition is specifically reversible by 0.1 mM L-methionine. In the same conditions even 1-2 mM MAMP has a very slight effect on the growth rate of P. aeruginosa and only during the first two generations. The same observation was made with the two other members of the fluorescens group P.fluorescens and P.putida. The growth rate of P. testosteroni with 1 mM MAMP in the medium is similar to the growth rate of P. aeruginosa but the other member of the acidovorans group P. acidovorans is much more affected by the smae concentration of the inhibitor. --P. multivorans is inhibited by MAMP like P. acidovorans but with a somewhat higher yield at the end of the culture. --MAMP has no effect on P. alcaligenes. The possible reasons for the weak bacteriostatic effect of MAMP on P. aeruginosa were investigated. It was established that the inhibitor enters the cells and is not used as a carbon and energy source. The intracellular methionine concentration in S. typhimurium and in P. aeruginosa is about the same and does not increase when bacteria are cultivated with MAMP. The MTS of the two microorganisms is inhibited by MAMP in vitro to about the same extent. Furthermore the tRNAmet from P. aeruginosa are fully acylated after 3 to 4 generations with this compound. Nevertheless MAMP elicits higher MTS activity in P. aeruginosa and in P. acidovorans after 1 h of incubation. The most striking difference between S. typhimurium and P. aeruginosa is that the intra and extracellular level of 5'phosphodiesterase which degrades MAMP is 10-20 fold higher in the second than in the first species."}
{"id": "PMID:189718", "title": "The site for catabolite deactivation in the L-arabinose BAD operon in Escherichia coli B/r.", "content": "A series of deletions beginning in the leu operon and continuing into the araC gene and also into the ara controlling site region were analyzed in reciprocal merodiploids, e.g., F' A2Cc67/B24delta719, F' B24delta719/A2Cc67, for their effects on catabolite deactivation (CD). The results of these experiments are consistent with placing the catabolite gene activator-cyclic AMP sensitive site in the controlling site region between araB and araO. With a deletion mutant, delta1109, that places araBAD under leu control when transcription begins at leuP, the araBAD operon is immune to CD even though araCGA, araP and araI are intact and functional. To focus attention on the fine structure and related functions of this region we propose that the three proteins that function therein have separate sites of action: araI (initiator-site for activator), araP (promoter-site for RNA polymerase) and ara(CGA) (catabolite gene activator-site for CGA-cAMP). None of the eighteen initiator constitutive mutants (Ic) tested have any significant effect on catabolite derepression or on the maximal level of expression of the operon supporting the view that the araI site may be distinct from araP and ARA(CGA). A series of constitutive mutants in the araC gene (Cc) also have no pronounced effect on catabolite deactivation.", "contents": "The site for catabolite deactivation in the L-arabinose BAD operon in Escherichia coli B/r. A series of deletions beginning in the leu operon and continuing into the araC gene and also into the ara controlling site region were analyzed in reciprocal merodiploids, e.g., F' A2Cc67/B24delta719, F' B24delta719/A2Cc67, for their effects on catabolite deactivation (CD). The results of these experiments are consistent with placing the catabolite gene activator-cyclic AMP sensitive site in the controlling site region between araB and araO. With a deletion mutant, delta1109, that places araBAD under leu control when transcription begins at leuP, the araBAD operon is immune to CD even though araCGA, araP and araI are intact and functional. To focus attention on the fine structure and related functions of this region we propose that the three proteins that function therein have separate sites of action: araI (initiator-site for activator), araP (promoter-site for RNA polymerase) and ara(CGA) (catabolite gene activator-site for CGA-cAMP). None of the eighteen initiator constitutive mutants (Ic) tested have any significant effect on catabolite derepression or on the maximal level of expression of the operon supporting the view that the araI site may be distinct from araP and ARA(CGA). A series of constitutive mutants in the araC gene (Cc) also have no pronounced effect on catabolite deactivation."}
{"id": "PMID:189719", "title": "Pyrimidine ribonucleoside monophosphokinase and the mode of RNA turnover in Bacillus subtilis.", "content": "A protein catalyzing the phosphorylation of CMP to CDP was purified and characterized. Kinase activity for UMP copurified during ammonium sulfate fractionation, DEAE-cellulose and hydroxylapatite chromatography, and gel filtration on Sephadex G-75, the ratios of activities for the two substrates remaining constant. The purified product, possessing both activities was homogeneous as judged by the single band following polyacrylamide gel electrophoresis. The protein showed no kinase activity against purine nucleoside monophosphates or the other pyrimidine nucleoside monophosphates: dCMP, dUMP, and dTMP. Thus unlike the enteric bacteria, Escherichia coli and Salmonella typhimurium which have distinct enzymes which phosphorylate UMP and CMP, Bacillus subtilis produces a single pyrimidine ribonucleoside monophosphokinase. The Km values of this enzyme from B.subtilis are 0.04 and 0.25 mM for CMP and UMP, respectively, and 0.04 and 0.4 mM for ATP at saturating concentrations of CMP and UMP, respectively. The properties of this enzyme and the differences between enteric bacteria and B.subtilis with respect to the enzymes which phosphorylate CMP are consistent with the measurements which indicate that turnover of messenger RNA is largely hydrolytic in E.coli but largely phosphorolytic in B.subtilis.", "contents": "Pyrimidine ribonucleoside monophosphokinase and the mode of RNA turnover in Bacillus subtilis. A protein catalyzing the phosphorylation of CMP to CDP was purified and characterized. Kinase activity for UMP copurified during ammonium sulfate fractionation, DEAE-cellulose and hydroxylapatite chromatography, and gel filtration on Sephadex G-75, the ratios of activities for the two substrates remaining constant. The purified product, possessing both activities was homogeneous as judged by the single band following polyacrylamide gel electrophoresis. The protein showed no kinase activity against purine nucleoside monophosphates or the other pyrimidine nucleoside monophosphates: dCMP, dUMP, and dTMP. Thus unlike the enteric bacteria, Escherichia coli and Salmonella typhimurium which have distinct enzymes which phosphorylate UMP and CMP, Bacillus subtilis produces a single pyrimidine ribonucleoside monophosphokinase. The Km values of this enzyme from B.subtilis are 0.04 and 0.25 mM for CMP and UMP, respectively, and 0.04 and 0.4 mM for ATP at saturating concentrations of CMP and UMP, respectively. The properties of this enzyme and the differences between enteric bacteria and B.subtilis with respect to the enzymes which phosphorylate CMP are consistent with the measurements which indicate that turnover of messenger RNA is largely hydrolytic in E.coli but largely phosphorolytic in B.subtilis."}
{"id": "PMID:189720", "title": "Glycollate production and excretion by Alcaligenes eutrophus.", "content": "Autotrophic cultures of the facultative chemolithotroph Alcaligenes eutrophus have been found to excrete glycollate. This excretion was greatly stimulated by the incorporation of up to 20% (v/v) oxygen in the hydrogen used for gassing. The stimulatory effect of oxygen was prevented by the addition of 10% (v/v) CO2 to the gassing mixture. Glycollate excretion only in the presence of oxygen was increased by the addition of 2-pyridyl-hydroxymethane sulphonic acid (HPMS), an inhibitor of glycollate oxidation, indicating that glycollate formation itself was stimulated by oxygen. No glycollate excretion by cultures grown heterotrophically on pyruvate was detected, either in the absence or presence of HPMS, under heterotrophic or autotrophic cells showed phosphoglycollate phosphatase and glycollate oxidoreductase activities, which were considerably lower in extracts prepared from pyruvate- or fructose-grown (heterotrophic) cells. The increase in activity of both enzymes upon cell transfer from heterotrophic to autotrophic growth was prevented by chloramphenicol and resembled the induction of D-ribulose 1,5-diphosphate carboxylase under the same conditions.", "contents": "Glycollate production and excretion by Alcaligenes eutrophus. Autotrophic cultures of the facultative chemolithotroph Alcaligenes eutrophus have been found to excrete glycollate. This excretion was greatly stimulated by the incorporation of up to 20% (v/v) oxygen in the hydrogen used for gassing. The stimulatory effect of oxygen was prevented by the addition of 10% (v/v) CO2 to the gassing mixture. Glycollate excretion only in the presence of oxygen was increased by the addition of 2-pyridyl-hydroxymethane sulphonic acid (HPMS), an inhibitor of glycollate oxidation, indicating that glycollate formation itself was stimulated by oxygen. No glycollate excretion by cultures grown heterotrophically on pyruvate was detected, either in the absence or presence of HPMS, under heterotrophic or autotrophic cells showed phosphoglycollate phosphatase and glycollate oxidoreductase activities, which were considerably lower in extracts prepared from pyruvate- or fructose-grown (heterotrophic) cells. The increase in activity of both enzymes upon cell transfer from heterotrophic to autotrophic growth was prevented by chloramphenicol and resembled the induction of D-ribulose 1,5-diphosphate carboxylase under the same conditions."}
{"id": "PMID:189721", "title": "Fumarate reduction in Proteus mirabilis.", "content": "1. Proteus mirabilis formed fumarate reductase under anaerobic growth conditions. The formation of this reductase was repressed under conditions of growth during which electron transport to oxygen or to nitrate is possible. In two of three tested chlorate-resistant mutant strains of the wild type, fumarate reductase appeared to be affected. 2. Cytoplasmic membrane suspensions isolated from anaerobically grown P. mirabilis oxidized formate and NADH with oxygen and with fumarate, too. 3. Spectral investigation of the cytoplasmic membrane preparation revealed the presence of (probably at least two types of) cytochrome b, cytochrome a1 and cytochrome d. Cytochrome b was reduced by NADH as well as by formate to approximately 80%. 4. 2-n-Heptyl-4-hydroxyquinilone-N-oxide and antimycin A inhibited oxidation of both formate and NADH by oxygen and fumarate. Both inhibitors increased the level of the formate/oxygen steady state and the formate/fumarate steady state. 5. The site of inhibition of the respiratory activity by both HQNO and antimycin A was located at the oxidation side of cytochrome b. 6. The effect of ultraviolet-irradiation of cytoplasmic membrane suspensions on oxidation/reduction phenomena suggested that the role of menaquinone is more exclusive in the formate/fumarate pathway than in the electron transport route to oxygen. 7. Finally, the conclusion has been drawn that the preferential route for electron transport from formate and from NADH to fumarate (and to oxygen) includes cytochrome b as a directly involved carrier. A hypothetical scheme for the electron transport in anaerobically grown P. mirabilis is presented.", "contents": "Fumarate reduction in Proteus mirabilis. 1. Proteus mirabilis formed fumarate reductase under anaerobic growth conditions. The formation of this reductase was repressed under conditions of growth during which electron transport to oxygen or to nitrate is possible. In two of three tested chlorate-resistant mutant strains of the wild type, fumarate reductase appeared to be affected. 2. Cytoplasmic membrane suspensions isolated from anaerobically grown P. mirabilis oxidized formate and NADH with oxygen and with fumarate, too. 3. Spectral investigation of the cytoplasmic membrane preparation revealed the presence of (probably at least two types of) cytochrome b, cytochrome a1 and cytochrome d. Cytochrome b was reduced by NADH as well as by formate to approximately 80%. 4. 2-n-Heptyl-4-hydroxyquinilone-N-oxide and antimycin A inhibited oxidation of both formate and NADH by oxygen and fumarate. Both inhibitors increased the level of the formate/oxygen steady state and the formate/fumarate steady state. 5. The site of inhibition of the respiratory activity by both HQNO and antimycin A was located at the oxidation side of cytochrome b. 6. The effect of ultraviolet-irradiation of cytoplasmic membrane suspensions on oxidation/reduction phenomena suggested that the role of menaquinone is more exclusive in the formate/fumarate pathway than in the electron transport route to oxygen. 7. Finally, the conclusion has been drawn that the preferential route for electron transport from formate and from NADH to fumarate (and to oxygen) includes cytochrome b as a directly involved carrier. A hypothetical scheme for the electron transport in anaerobically grown P. mirabilis is presented."}
{"id": "PMID:189722", "title": "The effect of dibromothymoquinone on respiratory and photosynthetic electron transport in Rhodopseudomonas capsulata chromatophores.", "content": "Dibromothymoquinone has been shown to inhibit light-induced cytochrome b reduction, and oxidation of succinate and NADH by chromatophores of Rhodopseudomonas capsulata. The half-inhibitory concentration of light-induced reactions and NADH oxidation is 2.5 muM, but of succinate oxidation is 16 muM. Hexane extraction inhibited oxidation of NADH and succinate equally. The results are interpreted to suggest that ubiquinone is concerned in all three processes described, but that the pools associated with NADH and succinate oxidation are not equally accessible to dibromothymoquinone.", "contents": "The effect of dibromothymoquinone on respiratory and photosynthetic electron transport in Rhodopseudomonas capsulata chromatophores. Dibromothymoquinone has been shown to inhibit light-induced cytochrome b reduction, and oxidation of succinate and NADH by chromatophores of Rhodopseudomonas capsulata. The half-inhibitory concentration of light-induced reactions and NADH oxidation is 2.5 muM, but of succinate oxidation is 16 muM. Hexane extraction inhibited oxidation of NADH and succinate equally. The results are interpreted to suggest that ubiquinone is concerned in all three processes described, but that the pools associated with NADH and succinate oxidation are not equally accessible to dibromothymoquinone."}
{"id": "PMID:189724", "title": "Fluphenazine decanoate, fluphenazine hydrochloride given orally, and placebo in remitted schizophrenics. I. Relapse rates after one year.", "content": "In a simple remitted, nonpsychotic schizophrenics, the relapse rate within one year was significantly higher for those patients taking placebo as opposed to those taking fluphenazine hydrochloride orally or fluphenazine decanoate. There were no differences in relapse rates between the two active drugs, but there were significantly more terminations due to toxicity from fluphenazine decanoate than from pluphenazine given orally, entirely due to the fact that in 35% of patients receiving fluphenazine decanoate, severe akinesia developed.", "contents": "Fluphenazine decanoate, fluphenazine hydrochloride given orally, and placebo in remitted schizophrenics. I. Relapse rates after one year. In a simple remitted, nonpsychotic schizophrenics, the relapse rate within one year was significantly higher for those patients taking placebo as opposed to those taking fluphenazine hydrochloride orally or fluphenazine decanoate. There were no differences in relapse rates between the two active drugs, but there were significantly more terminations due to toxicity from fluphenazine decanoate than from pluphenazine given orally, entirely due to the fact that in 35% of patients receiving fluphenazine decanoate, severe akinesia developed."}
{"id": "PMID:189725", "title": "Endogenous depression improvement and REM pressure.", "content": "In the treatment of endogenous depression by rapid eye movement (REM) sleep deprivation, depression improvement, measured on Hamilton and Global scales, correlated positively and significantly (P less than .05) with REM pressure (increase of REM sleep stimulated by REM sleep deprivation). This dose-response relationship suggests that (1) REM pressure was an indicator of a process that mediated the antidepressant effects of REM sleep deprivation, and (2) since improvement varied with stimulation of REM sleep, an unknown stimulus of REM sleep is a naturally occurring, endogenous antidepressant.", "contents": "Endogenous depression improvement and REM pressure. In the treatment of endogenous depression by rapid eye movement (REM) sleep deprivation, depression improvement, measured on Hamilton and Global scales, correlated positively and significantly (P less than .05) with REM pressure (increase of REM sleep stimulated by REM sleep deprivation). This dose-response relationship suggests that (1) REM pressure was an indicator of a process that mediated the antidepressant effects of REM sleep deprivation, and (2) since improvement varied with stimulation of REM sleep, an unknown stimulus of REM sleep is a naturally occurring, endogenous antidepressant."}
{"id": "PMID:189727", "title": "[Guillain Barr\u00e9- polyneuroradiculitis and Fisher-syndrome in cytomegalovirus infections (author's transl)].", "content": "In seven patients suffering from polyneuroradiculitis of the Guillain-Barr\u00e9 type and one case of Fisher syndrome, a cytomegalovirus infection was found. The elevation of the virus-specific IgM-antibodies was confirmed in all cases. The clinical course was severe and acute with respiratory disturbances, but complete remission occurred within 1-4 months. The complement fixing antibodies were highest during the first week of illness, so that further elevations could not be demonstrated, therefore making the IgM-antibody method of special importance. The role of cytomegalovirus infections in polyneuroradiculitis is also discussed.", "contents": "[Guillain Barr\u00e9- polyneuroradiculitis and Fisher-syndrome in cytomegalovirus infections (author's transl)]. In seven patients suffering from polyneuroradiculitis of the Guillain-Barr\u00e9 type and one case of Fisher syndrome, a cytomegalovirus infection was found. The elevation of the virus-specific IgM-antibodies was confirmed in all cases. The clinical course was severe and acute with respiratory disturbances, but complete remission occurred within 1-4 months. The complement fixing antibodies were highest during the first week of illness, so that further elevations could not be demonstrated, therefore making the IgM-antibody method of special importance. The role of cytomegalovirus infections in polyneuroradiculitis is also discussed."}
{"id": "PMID:189730", "title": "Replication of cytomegalovirus in human epitheloid diploid cell line.", "content": "Human diploid BAMB cells with epitheloid morphology, which had been derived from amniotic fluid cells, were capable of supporting the replication of human cytomegalovirus (CMV), without prior treatment of the cells with halogenated pyrimidines. The growth of this virus in BAMB cells and in human diploid fibroblastoid (LEP) cells was compared in parallel tests. Virus replication was slower and less efficient in the former than in the latter system. The most characteristic morphological feature of the CMV-infected BAMB cells was the formation of multinucleated giant cells which frequently contained more than a hundred nuclei; such cells were not seen in LEP cultures. The development of ultrastructural changes was slower in BAMB cells than in LEP cells. The additional most marked differences concerned the place of viral envelopment and the production of cytoplasmic dense bodies. While in LEP cells most nucleocapsids were enveloped from the inner leaflet of the nuclear membrane, in the other system a great majority of the particles acquired their envelopes by budding into vacuoles. Cytoplasmic dense bodies were rare in infected LEP cells but very frequent in BAMB cells. Budding of these structures into vacuoles was also observed.", "contents": "Replication of cytomegalovirus in human epitheloid diploid cell line. Human diploid BAMB cells with epitheloid morphology, which had been derived from amniotic fluid cells, were capable of supporting the replication of human cytomegalovirus (CMV), without prior treatment of the cells with halogenated pyrimidines. The growth of this virus in BAMB cells and in human diploid fibroblastoid (LEP) cells was compared in parallel tests. Virus replication was slower and less efficient in the former than in the latter system. The most characteristic morphological feature of the CMV-infected BAMB cells was the formation of multinucleated giant cells which frequently contained more than a hundred nuclei; such cells were not seen in LEP cultures. The development of ultrastructural changes was slower in BAMB cells than in LEP cells. The additional most marked differences concerned the place of viral envelopment and the production of cytoplasmic dense bodies. While in LEP cells most nucleocapsids were enveloped from the inner leaflet of the nuclear membrane, in the other system a great majority of the particles acquired their envelopes by budding into vacuoles. Cytoplasmic dense bodies were rare in infected LEP cells but very frequent in BAMB cells. Budding of these structures into vacuoles was also observed."}
{"id": "PMID:189733", "title": "[Morphological changes in the placenta in late pregnancy toxemias].", "content": "The article presents results of morphological, morphometric and cytochemical investigations of 100 placentae obtained in women who suffered from nephropathy of various degrees, and of placentae of mice with induced \"graft versus host\" reaction during pregnancy, and also of organs of two fetuses born to mothers who suffered from nephropathy of the III degree. In severe forms of late toxemia placentae, regularly showed infiltration of its structural elements with cells of the type of microlymphocytes with lytic properties. These changes occurred against the background of the placental metabolism turning into anaerobic respiration and they revealed a considerable degree of similarity to the changes in placentae of mice following the induction of the reaction \"graft versus host\". The morphological picture in lymphoid and other organs of the two investigated fetuses resembled very much that in \"runt\" disease.", "contents": "[Morphological changes in the placenta in late pregnancy toxemias]. The article presents results of morphological, morphometric and cytochemical investigations of 100 placentae obtained in women who suffered from nephropathy of various degrees, and of placentae of mice with induced \"graft versus host\" reaction during pregnancy, and also of organs of two fetuses born to mothers who suffered from nephropathy of the III degree. In severe forms of late toxemia placentae, regularly showed infiltration of its structural elements with cells of the type of microlymphocytes with lytic properties. These changes occurred against the background of the placental metabolism turning into anaerobic respiration and they revealed a considerable degree of similarity to the changes in placentae of mice following the induction of the reaction \"graft versus host\". The morphological picture in lymphoid and other organs of the two investigated fetuses resembled very much that in \"runt\" disease."}
{"id": "PMID:189734", "title": "[Theca-like reactions in the stroma of cilioepithelial ovarian neoplasms].", "content": "The work deals with the study of the so-called theca-like reaction in the stroma of 283 cilioepithelial tumours of the ovary (50 simple, 28 proliferating cystadenomas, and 205 cancers developed from cilioepithelial cystadenomas). The composition of the interstitial tissue of neoplasms of this type (except simple cystadenomas) included cells morphologically undistinguished from the thecal elements of the ovary. They may contain cholesterolethers and sets of redox enzymes typical of the steroidproducing tissues. Manifestation of the theca-like reaction (findings of morphometry) depended upon the degree of anaplasia of the tumour epithelium: it was most pronounced in malignant highly differentiated tumours, and least pronounced in drastically anaplasic cancer.", "contents": "[Theca-like reactions in the stroma of cilioepithelial ovarian neoplasms]. The work deals with the study of the so-called theca-like reaction in the stroma of 283 cilioepithelial tumours of the ovary (50 simple, 28 proliferating cystadenomas, and 205 cancers developed from cilioepithelial cystadenomas). The composition of the interstitial tissue of neoplasms of this type (except simple cystadenomas) included cells morphologically undistinguished from the thecal elements of the ovary. They may contain cholesterolethers and sets of redox enzymes typical of the steroidproducing tissues. Manifestation of the theca-like reaction (findings of morphometry) depended upon the degree of anaplasia of the tumour epithelium: it was most pronounced in malignant highly differentiated tumours, and least pronounced in drastically anaplasic cancer."}
{"id": "PMID:189735", "title": "[Electron microscopic diagnosis of granular cell tumors].", "content": "In tumour cells organspecific ultrastructural features are retained that may be of value in differential diagnosis. For this purpose not only fresh material but also that fixed formerly in formalin may be used.", "contents": "[Electron microscopic diagnosis of granular cell tumors]. In tumour cells organspecific ultrastructural features are retained that may be of value in differential diagnosis. For this purpose not only fresh material but also that fixed formerly in formalin may be used."}
{"id": "PMID:189736", "title": "[Cyclic nucleotides].", "content": "A survey of the available literature on the role of cyclic nucleotides (cyclic adenosine 3,5-monophosphate and cyclic guanosine 3,5-monophosphate) in the control over various aspects of cellular activity: regulation of growth and morphology of normal and tumorous cells, participation in differentiation of cells, blast-transformation, regulation of inflammatory and immunological processes governed by lymphocytes, is presented. A presumable mechanism of action of cyclic nucleotides is considered.", "contents": "[Cyclic nucleotides]. A survey of the available literature on the role of cyclic nucleotides (cyclic adenosine 3,5-monophosphate and cyclic guanosine 3,5-monophosphate) in the control over various aspects of cellular activity: regulation of growth and morphology of normal and tumorous cells, participation in differentiation of cells, blast-transformation, regulation of inflammatory and immunological processes governed by lymphocytes, is presented. A presumable mechanism of action of cyclic nucleotides is considered."}
{"id": "PMID:189737", "title": "Myosin degeneration in a congenital myopathy.", "content": "In a muscle biopsy specimen from a baby girl with hypotonia, there was the ultrastructural finding of selective myosin degeneration in some myofibers. The sarcomeres were either well aligned or completely distorted. Excessive glycogen, fiber and fibril splitting, and occasional aggregates of vesicles were the other abnormalities present.", "contents": "Myosin degeneration in a congenital myopathy. In a muscle biopsy specimen from a baby girl with hypotonia, there was the ultrastructural finding of selective myosin degeneration in some myofibers. The sarcomeres were either well aligned or completely distorted. Excessive glycogen, fiber and fibril splitting, and occasional aggregates of vesicles were the other abnormalities present."}
{"id": "PMID:189739", "title": "Optic nerve decompression. A clinical pathologic study.", "content": "Decompression of the perioptic meninges for intractable chronic papilledema was done in a patient with a right parietal temporal glioblastoma multiforme. The patient died 39 days postoperatively. Histologic study of the optic nerves indicated fistulas in the dura compatible with cerebrospinal fluid (CSF)  egress and maintenance of a normal subarachnoid space around the nerve. Two additional patients with unilateral optic nerve decompression producing bilateral resolution of papilledema were studied. We contend that egress of CSF was the principle mode of action in these three cases. How long the dural fistula remains patent is unknown. Reports in the literature show considerable variation in the effects of optic nerve decompression. Anatomic variation of the intracanalicular subarachnoid space together with differences in underlying pathologic condition, surgical technique, and patient response may explain discrepancies among the results reported.", "contents": "Optic nerve decompression. A clinical pathologic study. Decompression of the perioptic meninges for intractable chronic papilledema was done in a patient with a right parietal temporal glioblastoma multiforme. The patient died 39 days postoperatively. Histologic study of the optic nerves indicated fistulas in the dura compatible with cerebrospinal fluid (CSF)  egress and maintenance of a normal subarachnoid space around the nerve. Two additional patients with unilateral optic nerve decompression producing bilateral resolution of papilledema were studied. We contend that egress of CSF was the principle mode of action in these three cases. How long the dural fistula remains patent is unknown. Reports in the literature show considerable variation in the effects of optic nerve decompression. Anatomic variation of the intracanalicular subarachnoid space together with differences in underlying pathologic condition, surgical technique, and patient response may explain discrepancies among the results reported."}
{"id": "PMID:189740", "title": "Angiographic changes of head and neck chemodectomas following radiotherapy.", "content": "Angiography is useful in following selected patients with chemodectoma of the head and neck treated by radiotherapy. Comparison of preradiotherapy and post radiotherapy angiograms in three patients revealed a decrease in the following: size of feeding arteries, size of tumor, intensity of tumor opacification, and degree of venous shunting. When chemodectomas are not amenable to physical examination and when the question of radiotherapy complication vs further growth of tumor arises, postradiotheraphy angiography may be of particular value.", "contents": "Angiographic changes of head and neck chemodectomas following radiotherapy. Angiography is useful in following selected patients with chemodectoma of the head and neck treated by radiotherapy. Comparison of preradiotherapy and post radiotherapy angiograms in three patients revealed a decrease in the following: size of feeding arteries, size of tumor, intensity of tumor opacification, and degree of venous shunting. When chemodectomas are not amenable to physical examination and when the question of radiotherapy complication vs further growth of tumor arises, postradiotheraphy angiography may be of particular value."}
{"id": "PMID:189741", "title": "Prognosis of nasopharyngeal carcinoma by Epstein-Barr virus antibody titer.", "content": "A total of 433 samples of serum were collected from 305 patients with histopathologically proved anaplastic nasopharyngeal carcinoma (NPC). Antibodies against viral capsid antigens (VCA) of Epstein-Barr (EB) virus were titrated by means of indirect fluorescent antibody technique, using P3HR-1 cells as the target. High anti-VCA antibody titer in patients with NPC was found beginning to decline at the end of radiotherapy. Most (66.7%) of the patients were found to have a detectable reduction in antibody titer within six months after radiotherapy. Persistent high antibody titer after treatment correlates to high risk of the recurrence of the disease. This prognostic importance of anti-VCA titer becomes apparent at the end of radiotherapy, significant (P less than .05) within one year after treatment, and highly significant (P less than .0005) over one year after treatment.", "contents": "Prognosis of nasopharyngeal carcinoma by Epstein-Barr virus antibody titer. A total of 433 samples of serum were collected from 305 patients with histopathologically proved anaplastic nasopharyngeal carcinoma (NPC). Antibodies against viral capsid antigens (VCA) of Epstein-Barr (EB) virus were titrated by means of indirect fluorescent antibody technique, using P3HR-1 cells as the target. High anti-VCA antibody titer in patients with NPC was found beginning to decline at the end of radiotherapy. Most (66.7%) of the patients were found to have a detectable reduction in antibody titer within six months after radiotherapy. Persistent high antibody titer after treatment correlates to high risk of the recurrence of the disease. This prognostic importance of anti-VCA titer becomes apparent at the end of radiotherapy, significant (P less than .05) within one year after treatment, and highly significant (P less than .0005) over one year after treatment."}
{"id": "PMID:189742", "title": "[Electron microscopic examination on cytogenesis of juvenile nasopharyngeal angiofibromas (author's transl)].", "content": "After the electron miscroscopic examination of tissue samples of juvenile nasopharyngeal angiofibromas obtained from 9 male patients ranging in their age from 7-24 years the problems of cytogenesis and classification are discussed. Besides it is tried to correlate particular morphological findings to certain clinical phenomenons. The vascular component of juvenile nasopharyngeal angiofibromas shows a clear proliferation of the vascular wall cells. Particularly, proliferating pericytes, cells withous peculiar characteristics (\"undifferentiated\" cells) and cells in various stages of differentiation are to be emphasized. Obviously, vascular wall cells emigrate into the surrounding tissue and transform themselves into small fibroblasts. The second component of juvenil nasopharyngeal angiofibromas is represented by stromal fibroblasts with several cytological variations. Only activated \"classical\" fibroblasts and fibroblasts with histocyte-like features reveal the nuclear pattern unique for these growths which is characterized by the combination of protrusions of nuclear membrane with formation of nuclear \"blebs\" and of dense intranuclear granules. Cells with these nuclear characteristics were considered as preexisting fibroblasts. Thus juvenile nasopharyngeal angiofibromas are formed by the proliferation of two tissue components, namely by the proliferation of vascular wall cells and stromal fibroblasts, and can be conceived as reactive hyperplasias. The swelling body-like and organoid appearance, cytological pecularities, characteristic topographic relations (localization and supplying vessesl) and the sex-dependent occurrence speak for a tumor-like hyperplasia of a rudimentary organ unknown till now.", "contents": "[Electron microscopic examination on cytogenesis of juvenile nasopharyngeal angiofibromas (author's transl)]. After the electron miscroscopic examination of tissue samples of juvenile nasopharyngeal angiofibromas obtained from 9 male patients ranging in their age from 7-24 years the problems of cytogenesis and classification are discussed. Besides it is tried to correlate particular morphological findings to certain clinical phenomenons. The vascular component of juvenile nasopharyngeal angiofibromas shows a clear proliferation of the vascular wall cells. Particularly, proliferating pericytes, cells withous peculiar characteristics (\"undifferentiated\" cells) and cells in various stages of differentiation are to be emphasized. Obviously, vascular wall cells emigrate into the surrounding tissue and transform themselves into small fibroblasts. The second component of juvenil nasopharyngeal angiofibromas is represented by stromal fibroblasts with several cytological variations. Only activated \"classical\" fibroblasts and fibroblasts with histocyte-like features reveal the nuclear pattern unique for these growths which is characterized by the combination of protrusions of nuclear membrane with formation of nuclear \"blebs\" and of dense intranuclear granules. Cells with these nuclear characteristics were considered as preexisting fibroblasts. Thus juvenile nasopharyngeal angiofibromas are formed by the proliferation of two tissue components, namely by the proliferation of vascular wall cells and stromal fibroblasts, and can be conceived as reactive hyperplasias. The swelling body-like and organoid appearance, cytological pecularities, characteristic topographic relations (localization and supplying vessesl) and the sex-dependent occurrence speak for a tumor-like hyperplasia of a rudimentary organ unknown till now."}
{"id": "PMID:189743", "title": "Cytotoxic T cells in the peritoneal cavity of mice infected with ectromelia virus.", "content": "Peritoneal exudate cells from mice infected with ectromelia virus were cytotoxic for virus-infected target cells as measured in a 51Cr release assay. Cytotoxic activity seemed to be T cell-dependent as it was largely abolished by treatment with anti-theta serum and complement but was not impaired by macrophage depletion. The kinetics of development of cytotoxicity in the peritoneal cavity lagged behind spleen cytotoxicity by 1-2 days. Peak activity in peritoneal cells was present about 6 days after intravenous infection with virus. These studies suggest that macrophages present in the free peritoneal cell populations of ectromelia-infected mice are not cytotoxic for virus-infected target cells. The effect of macrophages in virus clearance is therefore likely to be due to phagocytic rather than cytotoxic effects.", "contents": "Cytotoxic T cells in the peritoneal cavity of mice infected with ectromelia virus. Peritoneal exudate cells from mice infected with ectromelia virus were cytotoxic for virus-infected target cells as measured in a 51Cr release assay. Cytotoxic activity seemed to be T cell-dependent as it was largely abolished by treatment with anti-theta serum and complement but was not impaired by macrophage depletion. The kinetics of development of cytotoxicity in the peritoneal cavity lagged behind spleen cytotoxicity by 1-2 days. Peak activity in peritoneal cells was present about 6 days after intravenous infection with virus. These studies suggest that macrophages present in the free peritoneal cell populations of ectromelia-infected mice are not cytotoxic for virus-infected target cells. The effect of macrophages in virus clearance is therefore likely to be due to phagocytic rather than cytotoxic effects."}
{"id": "PMID:189744", "title": "Metastatic hepatoma in the stomach masquerading as a leiomyoma.", "content": "Metastatic hepatoma in the stomach is rare. A case is described in which a gastric tumour appeared to be a leiomyoma, but after laparotomy proved to be an isolated secondary deposit from a hepatoma.", "contents": "Metastatic hepatoma in the stomach masquerading as a leiomyoma. Metastatic hepatoma in the stomach is rare. A case is described in which a gastric tumour appeared to be a leiomyoma, but after laparotomy proved to be an isolated secondary deposit from a hepatoma."}
{"id": "PMID:189745", "title": "Isolation of an adenovirus from an Arab foal with a combined immunode ficiency disease.", "content": "Some details of the clinical and postmortem findings of an Arab foal that died as a consequence of adenoviral pneumonia superimposed on a combined immunodeficiency disease are provided. The foal was the 17th in a series of similar deaths that occurred on a farm since 1959. An adenovirus, which by haemagglutination inhibition and serum neutralisation tests was antigenically similar to 2 other equine adenoviruses isolated in Australia, was isolated from a nasal swab taken from the foal when it was 23 days of age.", "contents": "Isolation of an adenovirus from an Arab foal with a combined immunode ficiency disease. Some details of the clinical and postmortem findings of an Arab foal that died as a consequence of adenoviral pneumonia superimposed on a combined immunodeficiency disease are provided. The foal was the 17th in a series of similar deaths that occurred on a farm since 1959. An adenovirus, which by haemagglutination inhibition and serum neutralisation tests was antigenically similar to 2 other equine adenoviruses isolated in Australia, was isolated from a nasal swab taken from the foal when it was 23 days of age."}
{"id": "PMID:189746", "title": "Changes in intestinal structure and function of neonatal calves infected with reovirus-like agent and Eschericia coli.", "content": "Measurements of villus/crypt length ratio and mucosal beta-galactosidase activity were made on calves less than 3 weeks of age which had diarrhoea associated with reovirus-like agent and E. coli. In calves with diarrhoea, the villus/crypt length ratios at all sites examined along the small intestine were less than in normal calves of similar age. This was attributed to a reduction in length of vili in calves infected with the reovirus-like agent. The activity of mucosal beta-galactosidase in the intestine of calves with diarrhoea was less than in normal calves, at all sites examined. A relationship existed between beta-galactosidase activity in vitro and lactose hydrolysis in vivo. It was concluded that calves with diarrhoea associated with reovirus-like agent, have a reduced ability to utilize dietary lactose.", "contents": "Changes in intestinal structure and function of neonatal calves infected with reovirus-like agent and Eschericia coli. Measurements of villus/crypt length ratio and mucosal beta-galactosidase activity were made on calves less than 3 weeks of age which had diarrhoea associated with reovirus-like agent and E. coli. In calves with diarrhoea, the villus/crypt length ratios at all sites examined along the small intestine were less than in normal calves of similar age. This was attributed to a reduction in length of vili in calves infected with the reovirus-like agent. The activity of mucosal beta-galactosidase in the intestine of calves with diarrhoea was less than in normal calves, at all sites examined. A relationship existed between beta-galactosidase activity in vitro and lactose hydrolysis in vivo. It was concluded that calves with diarrhoea associated with reovirus-like agent, have a reduced ability to utilize dietary lactose."}
{"id": "PMID:189747", "title": "Tenosynovitis in chickens.", "content": "An adenovirus was isolated from the tendon fluid of broilers and meat breeders with clinical tenosynovitis. The viral infection was in many cases accompanied by a staphylococcal infection. The significance of the adenovirus is not yet known, although initial transmission studies indicate that it may play a role in the tendon thickening process.", "contents": "Tenosynovitis in chickens. An adenovirus was isolated from the tendon fluid of broilers and meat breeders with clinical tenosynovitis. The viral infection was in many cases accompanied by a staphylococcal infection. The significance of the adenovirus is not yet known, although initial transmission studies indicate that it may play a role in the tendon thickening process."}
{"id": "PMID:189749", "title": "Electron microscopic study of benign hepatoma in a patient on oral contraceptives.", "content": "Electron microscopic studies of a benign hepatoma in a 31-year-old women who was on contraceptive pills are presented. The electron microscopic picture showed highly differentiated liver cells with regularly developed bile canaliculi. The mitochondrial polymorphism, the formation of paracristalloids and the appearance of giant mitochondria were striking. The main change was the occurence of the numerous capillaries of varying caliber which were highly differentiated and formed an integral part of the tumor. On the basis of these finding the tumor is regarded as a benign mixed tumor. The well developed capillary system explaines the arteriographic characteristics and the frequent bleeding complications noted in the literature.", "contents": "Electron microscopic study of benign hepatoma in a patient on oral contraceptives. Electron microscopic studies of a benign hepatoma in a 31-year-old women who was on contraceptive pills are presented. The electron microscopic picture showed highly differentiated liver cells with regularly developed bile canaliculi. The mitochondrial polymorphism, the formation of paracristalloids and the appearance of giant mitochondria were striking. The main change was the occurence of the numerous capillaries of varying caliber which were highly differentiated and formed an integral part of the tumor. On the basis of these finding the tumor is regarded as a benign mixed tumor. The well developed capillary system explaines the arteriographic characteristics and the frequent bleeding complications noted in the literature."}
{"id": "PMID:189751", "title": "Induction of enzymes of the glycerophosphate pathway in leu-5 mutants of Neurospora crassa.", "content": "The inducible cytosolic glycerokinase and mitochondrial glycerol-3-phosphate dehydrogenase have been examined during the glycerol-specific induction in Neurospora crassa. Although both the fully induced levels and the respective rates of synthesis of these two enzymes were less than observed with wild-type cells, there were no major differences in the relative rates of induction of the glycerol-3-phosphate dehydrogenase at either permissive or restrictive temperatures. These results indicate that the processes involved in the assembly of this enzyme into the mitochondrial inner membrane are normal in a mutant lacking the mitochondrial leucyl tRNA synthetase and suggest that the functions of the mitochondrial synthetase may be replaced by those of the cytosolic leucyl tRNA synthetase.", "contents": "Induction of enzymes of the glycerophosphate pathway in leu-5 mutants of Neurospora crassa. The inducible cytosolic glycerokinase and mitochondrial glycerol-3-phosphate dehydrogenase have been examined during the glycerol-specific induction in Neurospora crassa. Although both the fully induced levels and the respective rates of synthesis of these two enzymes were less than observed with wild-type cells, there were no major differences in the relative rates of induction of the glycerol-3-phosphate dehydrogenase at either permissive or restrictive temperatures. These results indicate that the processes involved in the assembly of this enzyme into the mitochondrial inner membrane are normal in a mutant lacking the mitochondrial leucyl tRNA synthetase and suggest that the functions of the mitochondrial synthetase may be replaced by those of the cytosolic leucyl tRNA synthetase."}
{"id": "PMID:189748", "title": "\"Tonic\" and \"phasic\" mechanisms in the regulation of myocardial contractility.", "content": "Myocardial contractility can be regulated by two types of control mechanism. A \"tonic control mechanism\", which allows the heart to respond to sustained changes in circulatory dynamics, appears to operate through changes in the structure of various constituents of the myocardium, best understood of these being changes in the myosin molecule that cause alterations in both myosin ATPase activity and contractility. Beat-to-beat changes in myocardial contractility are affected by a \"phasic control mechanism\" that involves changes in at least five calcium fluxes in the myocardium. The effects of catecholamines, many of which appear to be mediated by cyclic AMP, can be understood in terms of the modification of several of the calcium fluxes involved in the phasic control of myocardial contractility.", "contents": "\"Tonic\" and \"phasic\" mechanisms in the regulation of myocardial contractility. Myocardial contractility can be regulated by two types of control mechanism. A \"tonic control mechanism\", which allows the heart to respond to sustained changes in circulatory dynamics, appears to operate through changes in the structure of various constituents of the myocardium, best understood of these being changes in the myosin molecule that cause alterations in both myosin ATPase activity and contractility. Beat-to-beat changes in myocardial contractility are affected by a \"phasic control mechanism\" that involves changes in at least five calcium fluxes in the myocardium. The effects of catecholamines, many of which appear to be mediated by cyclic AMP, can be understood in terms of the modification of several of the calcium fluxes involved in the phasic control of myocardial contractility."}
{"id": "PMID:189752", "title": "Correlation of protein kinase activation and testosterone production after stimulation of Leydig cells with luteinizing hormone.", "content": "The effect of different doses of luteinizing hormone on activation of protein kinases, cyclic AMP and testosterone production was studied in purified rat testis Leydig-cell preparations in the presence of 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor). In addition, the nature of the protein kinases present in these cells and other tissues was investigated. The following results were obtained. 1. With all the amounts of luteinizing hormone used (0.1-1000 ng/ml), both activation of protein kinase and stimulation of testosterone production were demonstrated. With the lowest amount of luteinizing hormone (0.1 ng/ml), an 8.4+/-0.9% (S.E.M.,n=6) stimulation of protein kinase activation occurred, increasing to 100% with 1000 ng/ml, compared with 3.2+/-1.0%(S.E.M.,n=7) and 100% stimulation of testosterone production with 0.1 and 100 ng/ml respectively. 2. With amounts of luteinizing hormone up to 1 ng/ml (which gave half-maximal stimulation of testosterone production) no detectable increases in net cyclic AMP production were obtained. With higher amounts of luteinizing hormone, cyclic AMP production increased, but maximal production was not reached with 1000 ng/ml. 3. Two isoenzymic forms of protein kinase were present in Leydig cells and seminiferous tubules; type I was eluted with 0.075 M-and type II with 0.22-0.25 m-NaCl from DEAE-cellulose columns. 4. The protein kinase activity was not affected by the presence of erythrocytes in the Leydig-cell preparation, but varied depending on the type of histone used as substrate (histone F2b greater than mixed greater than histone F1).", "contents": "Correlation of protein kinase activation and testosterone production after stimulation of Leydig cells with luteinizing hormone. The effect of different doses of luteinizing hormone on activation of protein kinases, cyclic AMP and testosterone production was studied in purified rat testis Leydig-cell preparations in the presence of 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor). In addition, the nature of the protein kinases present in these cells and other tissues was investigated. The following results were obtained. 1. With all the amounts of luteinizing hormone used (0.1-1000 ng/ml), both activation of protein kinase and stimulation of testosterone production were demonstrated. With the lowest amount of luteinizing hormone (0.1 ng/ml), an 8.4+/-0.9% (S.E.M.,n=6) stimulation of protein kinase activation occurred, increasing to 100% with 1000 ng/ml, compared with 3.2+/-1.0%(S.E.M.,n=7) and 100% stimulation of testosterone production with 0.1 and 100 ng/ml respectively. 2. With amounts of luteinizing hormone up to 1 ng/ml (which gave half-maximal stimulation of testosterone production) no detectable increases in net cyclic AMP production were obtained. With higher amounts of luteinizing hormone, cyclic AMP production increased, but maximal production was not reached with 1000 ng/ml. 3. Two isoenzymic forms of protein kinase were present in Leydig cells and seminiferous tubules; type I was eluted with 0.075 M-and type II with 0.22-0.25 m-NaCl from DEAE-cellulose columns. 4. The protein kinase activity was not affected by the presence of erythrocytes in the Leydig-cell preparation, but varied depending on the type of histone used as substrate (histone F2b greater than mixed greater than histone F1)."}
{"id": "PMID:189753", "title": "Calcium metabolism and amylase release in rat parotid acinar cells.", "content": "1. A method is described for the isolation of rat parotid acinar cells by controlled digestion of the gland with trypsin followed by collagenase. As judged by Trypan Blue exclusion, electron microscopy, water, electrolyte and ATP concentrations and release of amylase and lactate dehydrogenase, the cells are morphologically and functionally intact. 2. A method was developed for perifusion of acinar cells by embedding them in Sephadex  G-10. Release of amylase was stimulated by adrenaline (0.1-10muM), isoproternol (1 or 10 MUM), phenylephrine (1 muM), carbamoylcholine (0.1 or 1 muM), dibutyryl cycle AMP (2 MM), 3-isobutyl-1-methylxanthine (1mM) and ionophore A23187. The effects of phenylephrine, carbamoylcholine and ionophore A23187 required extracellular Ca2+, whereas the effects of adrenaline and isoproterenol did not. 3. The incorporation of 45Ca into parotid cells showed a rapidly equilibrating pool (1-2 min) corresponding to 15% of total Ca2+ and a slowly equilibrating pool (greater than 3h) of probably a similar dimension. Cholinergic and alpha-adrenergic effectors and ionophore A23187 and 2,4-dinitrophenol increased the rate of incorporation of 45Ca into a slowly equilibrating pool, whereas beta-adrenergic effectors and dibutyryl cyclic AMP were inactive. 4. The efflux of 45Ca from cells into Ca2+-free medium was inhibited by phenylephrine and carbamoylcholine and accelerated by isoproterenol, adrenaline (beta-adrenergic effect), dibutyryl cyclic AMP and ionophore A23187. 5. A method was developed for the measurement of exchangeable 45Ca in mitochondria in parotid pieces. Incorporation of 45Ca into mitochondria was decreased by isoproterenol, dibutyryl cyclic AMP or 2,4-dinitrophenol, increased by adrenaline, and not changed significantly by phenylephrine or carbamoylcholine. Release of 45Ca from mitochondria in parotid pieced incubated in a Ca2+-free medium was increased by isoproterenol, adrenaline, dibutyryl cyclic AMP or 2,4-dinitrophenol and unaffected by phenylephrine or carbamoylcholine. 6. These findings are compatible with a role for Ca2+ as a mediator of amylase-secretory responses in rat parotid acinar cells, but no definite conclusions about its role can be drawn in the absence of knowledge of the molecular mechanisms involved, their location, and free Ca2+ concentration in appropriate cell compartment(s).", "contents": "Calcium metabolism and amylase release in rat parotid acinar cells. 1. A method is described for the isolation of rat parotid acinar cells by controlled digestion of the gland with trypsin followed by collagenase. As judged by Trypan Blue exclusion, electron microscopy, water, electrolyte and ATP concentrations and release of amylase and lactate dehydrogenase, the cells are morphologically and functionally intact. 2. A method was developed for perifusion of acinar cells by embedding them in Sephadex  G-10. Release of amylase was stimulated by adrenaline (0.1-10muM), isoproternol (1 or 10 MUM), phenylephrine (1 muM), carbamoylcholine (0.1 or 1 muM), dibutyryl cycle AMP (2 MM), 3-isobutyl-1-methylxanthine (1mM) and ionophore A23187. The effects of phenylephrine, carbamoylcholine and ionophore A23187 required extracellular Ca2+, whereas the effects of adrenaline and isoproterenol did not. 3. The incorporation of 45Ca into parotid cells showed a rapidly equilibrating pool (1-2 min) corresponding to 15% of total Ca2+ and a slowly equilibrating pool (greater than 3h) of probably a similar dimension. Cholinergic and alpha-adrenergic effectors and ionophore A23187 and 2,4-dinitrophenol increased the rate of incorporation of 45Ca into a slowly equilibrating pool, whereas beta-adrenergic effectors and dibutyryl cyclic AMP were inactive. 4. The efflux of 45Ca from cells into Ca2+-free medium was inhibited by phenylephrine and carbamoylcholine and accelerated by isoproterenol, adrenaline (beta-adrenergic effect), dibutyryl cyclic AMP and ionophore A23187. 5. A method was developed for the measurement of exchangeable 45Ca in mitochondria in parotid pieces. Incorporation of 45Ca into mitochondria was decreased by isoproterenol, dibutyryl cyclic AMP or 2,4-dinitrophenol, increased by adrenaline, and not changed significantly by phenylephrine or carbamoylcholine. Release of 45Ca from mitochondria in parotid pieced incubated in a Ca2+-free medium was increased by isoproterenol, adrenaline, dibutyryl cyclic AMP or 2,4-dinitrophenol and unaffected by phenylephrine or carbamoylcholine. 6. These findings are compatible with a role for Ca2+ as a mediator of amylase-secretory responses in rat parotid acinar cells, but no definite conclusions about its role can be drawn in the absence of knowledge of the molecular mechanisms involved, their location, and free Ca2+ concentration in appropriate cell compartment(s)."}
{"id": "PMID:189754", "title": "Studies on rat ovarian receptors for lutropin (luteinizing hormone). Applicability of radioimmunoassay to measure lutropin bound to receptors.", "content": "Measurement of receptor-bound unlabelled physiologically active lutropin (luteinizing hormone, LH) was possible by a modified radioimmunoassay. The conventional radioimmunoassay conducted at 4 degrees C was inadequate, whereas the modified assay performed at 37 degrees C could measure receptor-bound lutropin. The radioimmunoassay at 37 degrees C takes only 36h for completion compared with 5-7 days at 4 degreesC. The sensitivity and range of dose-response curves are, however, unaltered. The validity of the technique was established by a number of criteria.", "contents": "Studies on rat ovarian receptors for lutropin (luteinizing hormone). Applicability of radioimmunoassay to measure lutropin bound to receptors. Measurement of receptor-bound unlabelled physiologically active lutropin (luteinizing hormone, LH) was possible by a modified radioimmunoassay. The conventional radioimmunoassay conducted at 4 degrees C was inadequate, whereas the modified assay performed at 37 degrees C could measure receptor-bound lutropin. The radioimmunoassay at 37 degrees C takes only 36h for completion compared with 5-7 days at 4 degreesC. The sensitivity and range of dose-response curves are, however, unaltered. The validity of the technique was established by a number of criteria."}
{"id": "PMID:189755", "title": "Studies on rat ovarian receptors for lutropin (luteinizing hormone). Factors influencing binding and response.", "content": "The interaction of rat ovarian receptors with lutropin (luteinizing hormone, LH) in vitro was rapid and reversible. The degree of binding was saturable and susceptible  to changes in the concentration of lutropin in the medium. The concentration of lutropin receptors in the ovary increases during the natural pubertal period and also in immature rats given pregnant-mare-serum gonadotropin and human choriogonadotropin. In the latter case, the increase in lutropin receptor, after injection of pregnant-mare-serum gonadotropin alone, could be detected only if the ovaries are freed of the bound gonadotropin before exposure to lutropin. The concentration of lutropin receptors was higher in the luteal compartment of the ovary than in the non-luteal parts and increased slightly in aged corpora lutea. Correlation between binding of lutropin to the ovary and the ovarian response to lutropin in terms of cyclic AMP production was found only in prepubertal rat ovaries and in young corpora lutea and not in aged corpora lutea, suggesting the non-equivalence of binding in vitro and ovarian response.", "contents": "Studies on rat ovarian receptors for lutropin (luteinizing hormone). Factors influencing binding and response. The interaction of rat ovarian receptors with lutropin (luteinizing hormone, LH) in vitro was rapid and reversible. The degree of binding was saturable and susceptible  to changes in the concentration of lutropin in the medium. The concentration of lutropin receptors in the ovary increases during the natural pubertal period and also in immature rats given pregnant-mare-serum gonadotropin and human choriogonadotropin. In the latter case, the increase in lutropin receptor, after injection of pregnant-mare-serum gonadotropin alone, could be detected only if the ovaries are freed of the bound gonadotropin before exposure to lutropin. The concentration of lutropin receptors was higher in the luteal compartment of the ovary than in the non-luteal parts and increased slightly in aged corpora lutea. Correlation between binding of lutropin to the ovary and the ovarian response to lutropin in terms of cyclic AMP production was found only in prepubertal rat ovaries and in young corpora lutea and not in aged corpora lutea, suggesting the non-equivalence of binding in vitro and ovarian response."}
{"id": "PMID:189756", "title": "Studies on rat ovarian receptors for lutropin (luteinizing hormone). Interaction with beta-subunit of sheep lutropin.", "content": "By using radioimmunoassay, the interaction of sheep lutropin (luteinizing hormone, LH) beta-subunit with rat ovarian receptors was investigated. The binding of beta-subunit was specific, although of much lower order than that of lutropin. Sheep lutropin beta-subunit effectively inhibited the binding of human choriogonadotropin (chorionic gonadotropin, gCG) to the ovary, showing that both occupy the same sites. The binding of sheep lutropin beta-subunit to ovary was not followed by any detectable increase in cyclic AMP. The ovarian response to lutropin in terms of cyclic AMP production was inhibited in the presence of free beta-subunit. The alpha-subunit of lutropin, when used at concentrations where contamination with whole lutropin was negligible, enhanced the degree of binding of beta-subunit; this did not lead to increased cyclic AMP in the tissue. Surprisingly, the binding of beta-subunit in vitro was drastically decreased by the prior removal of all endogenous rat lutropin bound to receptors. The implications of these data are discussed in the light of the reported biological activity of the beta-subunit.", "contents": "Studies on rat ovarian receptors for lutropin (luteinizing hormone). Interaction with beta-subunit of sheep lutropin. By using radioimmunoassay, the interaction of sheep lutropin (luteinizing hormone, LH) beta-subunit with rat ovarian receptors was investigated. The binding of beta-subunit was specific, although of much lower order than that of lutropin. Sheep lutropin beta-subunit effectively inhibited the binding of human choriogonadotropin (chorionic gonadotropin, gCG) to the ovary, showing that both occupy the same sites. The binding of sheep lutropin beta-subunit to ovary was not followed by any detectable increase in cyclic AMP. The ovarian response to lutropin in terms of cyclic AMP production was inhibited in the presence of free beta-subunit. The alpha-subunit of lutropin, when used at concentrations where contamination with whole lutropin was negligible, enhanced the degree of binding of beta-subunit; this did not lead to increased cyclic AMP in the tissue. Surprisingly, the binding of beta-subunit in vitro was drastically decreased by the prior removal of all endogenous rat lutropin bound to receptors. The implications of these data are discussed in the light of the reported biological activity of the beta-subunit."}
{"id": "PMID:189757", "title": "Vitamin D in the avian egg. Its molecular identity and mechanism of incorporation into yolk.", "content": "The chemical identity of vitamin D in the egg of the domestic fowl was studied by analysing radioactivity in eggs from hens injected with [3H]cholecalciferol. Labelled molecules were found throughout the egg, but the concentration of total radioactivity in albumin was only 5-7% of that in yolk. In lipid extracts of yolk, more than 90% of the radioactivity was as unchanged cholecalciferol and 5% as 25-hydroxycholecalciferol. Only about 3% of the radioactivity in albumin was chloroform-soluble, and of this 40% was 25-hydroxycholecalciferol and 15% was cholecalciferol. Evidence is presented to support the idea that the specific transport of cholecalciferol into yolk is mediated by a cholecalciferol-binding protein in blood. This protein forms a complex with yolk proteins in transit from liver to ovary via the blood. A cholecalciferol-binding protein, chromatographically similar to that from blood, was found in egg yolk. It is postulated that cholecalciferol forms part of a complex with its specific binding protein, Ca2+ and the yolk phosphoprotein, phosvitin. This complex is then incorporated into yolk by the thecal cells of the ovarian follicle.", "contents": "Vitamin D in the avian egg. Its molecular identity and mechanism of incorporation into yolk. The chemical identity of vitamin D in the egg of the domestic fowl was studied by analysing radioactivity in eggs from hens injected with [3H]cholecalciferol. Labelled molecules were found throughout the egg, but the concentration of total radioactivity in albumin was only 5-7% of that in yolk. In lipid extracts of yolk, more than 90% of the radioactivity was as unchanged cholecalciferol and 5% as 25-hydroxycholecalciferol. Only about 3% of the radioactivity in albumin was chloroform-soluble, and of this 40% was 25-hydroxycholecalciferol and 15% was cholecalciferol. Evidence is presented to support the idea that the specific transport of cholecalciferol into yolk is mediated by a cholecalciferol-binding protein in blood. This protein forms a complex with yolk proteins in transit from liver to ovary via the blood. A cholecalciferol-binding protein, chromatographically similar to that from blood, was found in egg yolk. It is postulated that cholecalciferol forms part of a complex with its specific binding protein, Ca2+ and the yolk phosphoprotein, phosvitin. This complex is then incorporated into yolk by the thecal cells of the ovarian follicle."}
{"id": "PMID:189758", "title": "Intramitochondrial positions of cytochrome haem groups determined by dipolar interactions with paramagnetic cations.", "content": "E.p.r.(electron-paramagnetic-resonance) spectra of the ferricytochromes were studied in normal and 'nickel-plated' pigeon heart mitochondria and pigeon heart submitochondrial particles. NiCL2 added to either mitochondria or particles was bound completely to the membranes, but none was transported across the vesicles. Hence, any perturbations of the haem e.p.r. spectra by Ni(II) should occur only for those cytochromes in close proximity to the exterior surface. Whenever Ni(II) can approach to within 1 nm of cytochrome haem. the consequent acceleration of the haem e.p.r. relaxation kinetics should elicit dipolar line broadening. Relaxation acceleration should also increase the incident power level required to saturate the haem e.p.r. signal. In pigeon heart mitochondria, at least three e.p.r. resonances, attributable in part to cytochromes c1, bK and br, are observed at gz=3.3 resonance. In these submitochondrial particles, the peak at gz=3.5 is missing, and the resonance at gz=3.6 resolves into two components, neither of which is sensitive to added Ni(ii). Addition of free haemin (ferric, a paramagnetic anion) to intact mitochondria elicits the same e.p.r. signal changes as does a preparation of submitochondrial particles. Saturation curves for cytochrome oxidase obtained for e.p.r. spectra of the high-spin form (g = 6) and the low-spin form (gz=3.1) also reveal no effect of Ni(II) on the haem e.p.r. relaxation in either mitochondria or inverted submitochondrial particles. Further, Ni(II) fails to alter the spectra or saturation properties of cytochrome c in either mitochondria or submitochondrial particles therefrom. Only with a 50-fold molar excess of Ni(II) can one accelerate the e.p.r. relaxation of cytochrome c in aqueous solution, although other more subtle types of magnetic interactions may occur between the cytochrome and either Ni(II) or ferricyanide. Addition of haemin to mitochondria likewise failed to alter the e.p.r. characteristics of either cytochrome c or cytochrome oxidase. The present observations strongly suggest that cytochromes bK, br and c1 reside on the exterior surface of the inner mitochondrial membrane. On the other hand, we find no positive evidence for the location of cytochrome c or cytochrome oxidase haem groups within 1 nm of either membrane surface. Because of possible shielding effects from the protein moieties, however, we cannot unequivocally assign the location of the haem groups to the membrane interior. The present results are not inconsistent with the observations of other investigators who used different techniques. However, it is clear that any model of energy coupling in mitochondrial oxidative phosphorylation must account for the positioning of all the b-c cytochrome haem groups on the outside.", "contents": "Intramitochondrial positions of cytochrome haem groups determined by dipolar interactions with paramagnetic cations. E.p.r.(electron-paramagnetic-resonance) spectra of the ferricytochromes were studied in normal and 'nickel-plated' pigeon heart mitochondria and pigeon heart submitochondrial particles. NiCL2 added to either mitochondria or particles was bound completely to the membranes, but none was transported across the vesicles. Hence, any perturbations of the haem e.p.r. spectra by Ni(II) should occur only for those cytochromes in close proximity to the exterior surface. Whenever Ni(II) can approach to within 1 nm of cytochrome haem. the consequent acceleration of the haem e.p.r. relaxation kinetics should elicit dipolar line broadening. Relaxation acceleration should also increase the incident power level required to saturate the haem e.p.r. signal. In pigeon heart mitochondria, at least three e.p.r. resonances, attributable in part to cytochromes c1, bK and br, are observed at gz=3.3 resonance. In these submitochondrial particles, the peak at gz=3.5 is missing, and the resonance at gz=3.6 resolves into two components, neither of which is sensitive to added Ni(ii). Addition of free haemin (ferric, a paramagnetic anion) to intact mitochondria elicits the same e.p.r. signal changes as does a preparation of submitochondrial particles. Saturation curves for cytochrome oxidase obtained for e.p.r. spectra of the high-spin form (g = 6) and the low-spin form (gz=3.1) also reveal no effect of Ni(II) on the haem e.p.r. relaxation in either mitochondria or inverted submitochondrial particles. Further, Ni(II) fails to alter the spectra or saturation properties of cytochrome c in either mitochondria or submitochondrial particles therefrom. Only with a 50-fold molar excess of Ni(II) can one accelerate the e.p.r. relaxation of cytochrome c in aqueous solution, although other more subtle types of magnetic interactions may occur between the cytochrome and either Ni(II) or ferricyanide. Addition of haemin to mitochondria likewise failed to alter the e.p.r. characteristics of either cytochrome c or cytochrome oxidase. The present observations strongly suggest that cytochromes bK, br and c1 reside on the exterior surface of the inner mitochondrial membrane. On the other hand, we find no positive evidence for the location of cytochrome c or cytochrome oxidase haem groups within 1 nm of either membrane surface. Because of possible shielding effects from the protein moieties, however, we cannot unequivocally assign the location of the haem groups to the membrane interior. The present results are not inconsistent with the observations of other investigators who used different techniques. However, it is clear that any model of energy coupling in mitochondrial oxidative phosphorylation must account for the positioning of all the b-c cytochrome haem groups on the outside."}
{"id": "PMID:189759", "title": "Intramitochondrial positions of ubiquinone and iron-sulphur centres determined by dipolar interactions with paramagnetic ions.", "content": "E.p.r. (electron-paramagnetic-resonance) spectra of ubisemiquinone (QH) organic radicals and all of the known iron-sulphur centres were studied in normal and 'nickle-plated' pigeon heart mitochondria, submitochondrial particles and submitochondrial particles from which succinate dehydrogenase had been removed. Incubation of pigeon heart mitochondria, submitochondrial particles or succinate dehydrogenase-depleted submitochondrial particles with substrate in the presence of pure O2 results in the accumulation of Q-H. In mitochondria, the e.p.r. spectrum of Q-H is characterized by in-homogeneous line broadening. A heterogeneous population of semiquinones appears to be partly responsible for these effects in mitochondria. Additon of Ni(II) to mitochondria renders saturation of the Q-H resonance more difficult. On the other hand, the resonance in either submitochondrial particles or succinate dehydrogenase-depleted particles is narrower than the same spectrum in mitochondria, and saturates like a homogeneous line. The presence of Ni(II) in either of these preparations, further, has no effect on either the A-H spectrum or the saturation curve. Therefore QH appears to be situated on the exterior surface of the mitochondrion. Likewise, the e.p.r. spectra and saturation curves of iron-sulphur centre N-2 exhibit characteristics of inhomogeneous line broadening, not only in intact mitochondria but also in both submitochondrial particles and succinate dehydrogenase-depleted particles. Because of the small pool size of centre N-2, this effect is likely to arise from a spin interaction with some other component in the membrane. Ni(II) has no effect on the saturation in centre N-2 in mitochondria or submitochondrial particles, and only a marginal effect in the succinate dehydrogenase-depleted preparation. These results are indeterminate with respect to the position of centre N-2 in the membrane; but suggest that its distance from the succinate dehydrogenase binding site is on the order of 1 nm. All of the other ferredoxin-type iron-sulphur centres in both preparations were not affected by paramagnetic ions. Homogeneous e.p.r. spectra and saturation curves are observed for both of the HiPIP-type (high-potential iron-sulphur protein-type) iron-sulphur centres in mitochondrial centres S-3 and bc-3. Addition of No(II) to intact mitochondria results in a dipolar interaction with centre bc-3. No effect was observed on centre S-3 in either preparation. A comprehensive model is presented for the structure of the respiratory electron-transport system in mitochondria, based on e.p.r. relaxation studies in the present and the preceding paper. There is no direct evidence for transmembrane electron flow through any of the known energy-coupling sites in mitochondria, so that direct hydrogen atom transfer across the membrane (as a combination of H+ translocation coupled to electron flow) does not occur...", "contents": "Intramitochondrial positions of ubiquinone and iron-sulphur centres determined by dipolar interactions with paramagnetic ions. E.p.r. (electron-paramagnetic-resonance) spectra of ubisemiquinone (QH) organic radicals and all of the known iron-sulphur centres were studied in normal and 'nickle-plated' pigeon heart mitochondria, submitochondrial particles and submitochondrial particles from which succinate dehydrogenase had been removed. Incubation of pigeon heart mitochondria, submitochondrial particles or succinate dehydrogenase-depleted submitochondrial particles with substrate in the presence of pure O2 results in the accumulation of Q-H. In mitochondria, the e.p.r. spectrum of Q-H is characterized by in-homogeneous line broadening. A heterogeneous population of semiquinones appears to be partly responsible for these effects in mitochondria. Additon of Ni(II) to mitochondria renders saturation of the Q-H resonance more difficult. On the other hand, the resonance in either submitochondrial particles or succinate dehydrogenase-depleted particles is narrower than the same spectrum in mitochondria, and saturates like a homogeneous line. The presence of Ni(II) in either of these preparations, further, has no effect on either the A-H spectrum or the saturation curve. Therefore QH appears to be situated on the exterior surface of the mitochondrion. Likewise, the e.p.r. spectra and saturation curves of iron-sulphur centre N-2 exhibit characteristics of inhomogeneous line broadening, not only in intact mitochondria but also in both submitochondrial particles and succinate dehydrogenase-depleted particles. Because of the small pool size of centre N-2, this effect is likely to arise from a spin interaction with some other component in the membrane. Ni(II) has no effect on the saturation in centre N-2 in mitochondria or submitochondrial particles, and only a marginal effect in the succinate dehydrogenase-depleted preparation. These results are indeterminate with respect to the position of centre N-2 in the membrane; but suggest that its distance from the succinate dehydrogenase binding site is on the order of 1 nm. All of the other ferredoxin-type iron-sulphur centres in both preparations were not affected by paramagnetic ions. Homogeneous e.p.r. spectra and saturation curves are observed for both of the HiPIP-type (high-potential iron-sulphur protein-type) iron-sulphur centres in mitochondrial centres S-3 and bc-3. Addition of No(II) to intact mitochondria results in a dipolar interaction with centre bc-3. No effect was observed on centre S-3 in either preparation. A comprehensive model is presented for the structure of the respiratory electron-transport system in mitochondria, based on e.p.r. relaxation studies in the present and the preceding paper. There is no direct evidence for transmembrane electron flow through any of the known energy-coupling sites in mitochondria, so that direct hydrogen atom transfer across the membrane (as a combination of H+ translocation coupled to electron flow) does not occur..."}
{"id": "PMID:189777", "title": "Hypertriglyceridemia in the diabetic rat. Defective removal of serum very low density.", "content": "Streptozotocin-induced diabetic rats show a marked fasting hypertriglyceridemia. It appears that only the very low density lipoprotein (VLDL) fraction is increased. VLDL from either normal or diabetic rats was labelled in vivo in the triglyceride moiety with [3H]palmitate and isolated. Both preparations, if injected intravenously into recipient rats, are removed more slowly from the circulation of diabetic rats as compared to normal rats, resulting in a reduction of the fractional catabolic rate (F.C.R.) by 70%. However, the absolute catabolic rate (turnover) of VLDL triglycerides was not changed in diabetics. It is concluded that the hypertriglyceridemia of the the diabetic rat is caused by a defective removal mechanism of VLDL triglycerides. The F.C.R. of 125I-labelled low density lipoproteins and high density lipoproteins is only 1-3% of the value for VLDL triglycerides and unchanged in diabetic rats.", "contents": "Hypertriglyceridemia in the diabetic rat. Defective removal of serum very low density. Streptozotocin-induced diabetic rats show a marked fasting hypertriglyceridemia. It appears that only the very low density lipoprotein (VLDL) fraction is increased. VLDL from either normal or diabetic rats was labelled in vivo in the triglyceride moiety with [3H]palmitate and isolated. Both preparations, if injected intravenously into recipient rats, are removed more slowly from the circulation of diabetic rats as compared to normal rats, resulting in a reduction of the fractional catabolic rate (F.C.R.) by 70%. However, the absolute catabolic rate (turnover) of VLDL triglycerides was not changed in diabetics. It is concluded that the hypertriglyceridemia of the the diabetic rat is caused by a defective removal mechanism of VLDL triglycerides. The F.C.R. of 125I-labelled low density lipoproteins and high density lipoproteins is only 1-3% of the value for VLDL triglycerides and unchanged in diabetic rats."}
{"id": "PMID:189778", "title": "Intravenous fat tolerance. Correlation with very low density lipoprotein apoprotein B kinetics in man.", "content": "The intravenous fat tolerance test (IVFTT) has been introduced as a measure of the fractional catabolic rate of the endogenous triglyceride of plasma. To assess the validity of this test we have compared this test in 21 normal and hyperlipidaemic subjects with direct measurement of the fractional catabolic rate of autologous radio-iodinated VLDL. There was a strong positive correlation between the rate constant K2 of the IVFTT and the fractional catabolic rate of VLDL-apolipoprotein B (r=+0.87). The two rates were considerably different in magnitude. The IVFTT appears to be a valid index of the fractional catabolic rate of VLDL. Its limitations and uses are discussed.", "contents": "Intravenous fat tolerance. Correlation with very low density lipoprotein apoprotein B kinetics in man. The intravenous fat tolerance test (IVFTT) has been introduced as a measure of the fractional catabolic rate of the endogenous triglyceride of plasma. To assess the validity of this test we have compared this test in 21 normal and hyperlipidaemic subjects with direct measurement of the fractional catabolic rate of autologous radio-iodinated VLDL. There was a strong positive correlation between the rate constant K2 of the IVFTT and the fractional catabolic rate of VLDL-apolipoprotein B (r=+0.87). The two rates were considerably different in magnitude. The IVFTT appears to be a valid index of the fractional catabolic rate of VLDL. Its limitations and uses are discussed."}
{"id": "PMID:189779", "title": "Effect of phospholipids on cholesterol-induced modifications in mouse brain.", "content": "Mice on an atherogenic diet for 40 days show a decrease in brain content of catecholamines, cyclic AMP and in dopamine degradation, and modification of the glycolytic pathway. The metabolic changes are paralleled by changes in behaviour, i.e. decrease in spontaneous motor activity and in conditioning avoidance response. The decrease in dopamine degradation and in behaviour parameters is partly due to the propylthiouracil present in the diet. Endovenous treatment with sonicated dispersions of bovine brain phospholipids induces a modification in the parameters of behaviour and metabolism. The possibility is discussed that some of the defects arising during the atherogenic diet are related with the establishment of a hypoxic state.", "contents": "Effect of phospholipids on cholesterol-induced modifications in mouse brain. Mice on an atherogenic diet for 40 days show a decrease in brain content of catecholamines, cyclic AMP and in dopamine degradation, and modification of the glycolytic pathway. The metabolic changes are paralleled by changes in behaviour, i.e. decrease in spontaneous motor activity and in conditioning avoidance response. The decrease in dopamine degradation and in behaviour parameters is partly due to the propylthiouracil present in the diet. Endovenous treatment with sonicated dispersions of bovine brain phospholipids induces a modification in the parameters of behaviour and metabolism. The possibility is discussed that some of the defects arising during the atherogenic diet are related with the establishment of a hypoxic state."}
{"id": "PMID:189780", "title": "Metaformin: an antiatherosclerotic agent modifying very low density lipoproteins in rabbits.", "content": "The composition of very low density lipoproteins (VLDL: d less than 1.019) of New Zealand male rabbits reciving cholesterol (2 g/day) and metformin (135 mg/kg/day) is investigated. These rabbits, while showing only a slight reduction of plasma cholesterol levels, as compared to cholesterol-fed (h.c.) animals, show a marked decrease of the aortic cholesterol esters and atheromatous process. VLDL from the cholesterol + metformin group (h.c. + met), as compared to the h.c. animals, are homogenous in size and not separable into VLDL-1 and VLDL-2 subfractions by Sepharose 4B chromatography. These findings are confirmed by electron microscopy, which shows homogeneity of particle size, as well a decreased tendency of h.c. + met VLDL to aggregate. Chemical composition of h.c. + met VLDL is characterized by increased triglycerides and phospholipids, while the percentage of cholesterol esters is not significantly decreased. Phospholipid distribution of h.c. + met VLDL shows a significant decrease of sphingomyelin and increased phosphatidylinositol, the latter both as compared to h.c. and control VLDL. Apoprotein pattern of h.c. + met VLDL in polyacrylamide gels shows a relative increase of peptides with C mobility and a decrease of proteins corresponding to the arg-rich peptides. These findings exemplify a case of altered lipoprotein composition and decreased atheromatosis, in the presence of marked hypercholesteremia.", "contents": "Metaformin: an antiatherosclerotic agent modifying very low density lipoproteins in rabbits. The composition of very low density lipoproteins (VLDL: d less than 1.019) of New Zealand male rabbits reciving cholesterol (2 g/day) and metformin (135 mg/kg/day) is investigated. These rabbits, while showing only a slight reduction of plasma cholesterol levels, as compared to cholesterol-fed (h.c.) animals, show a marked decrease of the aortic cholesterol esters and atheromatous process. VLDL from the cholesterol + metformin group (h.c. + met), as compared to the h.c. animals, are homogenous in size and not separable into VLDL-1 and VLDL-2 subfractions by Sepharose 4B chromatography. These findings are confirmed by electron microscopy, which shows homogeneity of particle size, as well a decreased tendency of h.c. + met VLDL to aggregate. Chemical composition of h.c. + met VLDL is characterized by increased triglycerides and phospholipids, while the percentage of cholesterol esters is not significantly decreased. Phospholipid distribution of h.c. + met VLDL shows a significant decrease of sphingomyelin and increased phosphatidylinositol, the latter both as compared to h.c. and control VLDL. Apoprotein pattern of h.c. + met VLDL in polyacrylamide gels shows a relative increase of peptides with C mobility and a decrease of proteins corresponding to the arg-rich peptides. These findings exemplify a case of altered lipoprotein composition and decreased atheromatosis, in the presence of marked hypercholesteremia."}
{"id": "PMID:189776", "title": "[Researches on the water quality of the river Po and its tributaries between Cremona and Casalmaggiore. I. materials and methods (author's transl)].", "content": "During 1971 a research program about the status of pollution of the river Po and its tributaries was started by six Institutes of Hygiene altogether (Turin, Pavia, Milan, Parma, Modena and Ferrara Universities) with the Institute for Water Research of C.N.R. and Hydrographic Office of Magistracy of the Po. The role of the Parma University Hygiene Institute was to study the water qualities of the river Po between Cremona and Casalmaggiore and of two right side tributaries, Arda-Ongina and Taro. The hydrogeographical characteristics of the examined reach are reported in the present note, with special reference to the hydrological conditions, basin area, inhabitants and industrial typology. The sampling stations were placed upstream and downstream Cremona town, near Casalmaggiore and at the mouth of Arda-Ongina and Taro. Moreover the methods, for chemical and bacteriological analysis are reported.", "contents": "[Researches on the water quality of the river Po and its tributaries between Cremona and Casalmaggiore. I. materials and methods (author's transl)]. During 1971 a research program about the status of pollution of the river Po and its tributaries was started by six Institutes of Hygiene altogether (Turin, Pavia, Milan, Parma, Modena and Ferrara Universities) with the Institute for Water Research of C.N.R. and Hydrographic Office of Magistracy of the Po. The role of the Parma University Hygiene Institute was to study the water qualities of the river Po between Cremona and Casalmaggiore and of two right side tributaries, Arda-Ongina and Taro. The hydrogeographical characteristics of the examined reach are reported in the present note, with special reference to the hydrological conditions, basin area, inhabitants and industrial typology. The sampling stations were placed upstream and downstream Cremona town, near Casalmaggiore and at the mouth of Arda-Ongina and Taro. Moreover the methods, for chemical and bacteriological analysis are reported."}
{"id": "PMID:189781", "title": "High plasma cholesterol in mink (Mustela vison) without atherosclerosis.", "content": "Mink fed a commercial ration moderately high in cholesterol or fed a cholesterol-free semipurified diet have plasma cholesterol-free semipurified diet have plasma cholesterol concentrations similar to that found in human beings living in industrialized countries. In contrast with human beings, 80% of the plasma cholesterol in mink is carried in the high density lipoprotein fraction. Aortas and coronary arteries from animals up to 8 yr old were found to be free of fatty streaks and atherosclerotic plaques, both grossly and microscopically.", "contents": "High plasma cholesterol in mink (Mustela vison) without atherosclerosis. Mink fed a commercial ration moderately high in cholesterol or fed a cholesterol-free semipurified diet have plasma cholesterol-free semipurified diet have plasma cholesterol concentrations similar to that found in human beings living in industrialized countries. In contrast with human beings, 80% of the plasma cholesterol in mink is carried in the high density lipoprotein fraction. Aortas and coronary arteries from animals up to 8 yr old were found to be free of fatty streaks and atherosclerotic plaques, both grossly and microscopically."}
{"id": "PMID:189782", "title": "Metabolic effects of carbon monoxide in relation to atherogenesis.", "content": "The acute and chronic effects of carbon monoxide (CO) are reviewed. Direct effects of CO-induced hypoxia on arterial metabolism may facilitate deposition of cholesterol in the intimal surface and exacerbate existing atherosclerosis. Other studies indicate that CO may alter hepatic metabolism so as to inhibit both the secretion of very low density lipoproteins and the clearance of chylomicron remnants. The former change would diminish and the latter enhance atherogenesis. These findings are considered and avenues of future investigation suggested.", "contents": "Metabolic effects of carbon monoxide in relation to atherogenesis. The acute and chronic effects of carbon monoxide (CO) are reviewed. Direct effects of CO-induced hypoxia on arterial metabolism may facilitate deposition of cholesterol in the intimal surface and exacerbate existing atherosclerosis. Other studies indicate that CO may alter hepatic metabolism so as to inhibit both the secretion of very low density lipoproteins and the clearance of chylomicron remnants. The former change would diminish and the latter enhance atherogenesis. These findings are considered and avenues of future investigation suggested."}
{"id": "PMID:189783", "title": "Chemical composition of ultracentrifugal fractions in different patterns of human atheroslcerosis.", "content": "The chemical composition of ultracentrifugal fractions of VLDL (d less than 1006), LDL (d 1006-1063) and HDL (d less than 1063) has been studied in males affected by atherosclerosis of different vascular beds. Thirty-seven subjects affected by post-infarction cardiopathy (M.I.) showed significantly higher values of total-C, VLDL-C and LDL-C when compared to 52 controls. Twenty-three patients affected by non-occlusive ischaemic heart disease (I.H.D.) showed higher values than controls of total-C, VLCL-C, LDL-C, total TG, VLDL-TG, and GDL-TG. Twenty-three patients with atherosclerosis of the inferior limbs (P.A.) were characterized by increased levels of total-TG, VLDL-TG, VLDL-C, HDL-C. A group of patients who had suffered a stroke from cerebro-vascular disease (C.V.D.) did not show any significant difference from controls. In the M.I. group, 56% of the patients had a high level of C-VLDL. Patients with I.H.D. were characterized mostly by an increase in C-LDL, Patients with P.A. showed the highest values of total -TG, VLDL-TG and LDL-TG. Some of the observed differences are probably due to different metabolic backgrounds. Some other differences may be due to variations in dietary habits after heart infarction. Patients with levels of plasma cholesterol and triglyceride beyond the 90th percentile of the normal group showed many abnormalities in the chemical composition of their lipoproteins. It is noteworthy that increased amounts of cholesterol may collect in lipoprotein classes different from LDL while increased amounts of triglyceride may collect in classes different from VLDL.", "contents": "Chemical composition of ultracentrifugal fractions in different patterns of human atheroslcerosis. The chemical composition of ultracentrifugal fractions of VLDL (d less than 1006), LDL (d 1006-1063) and HDL (d less than 1063) has been studied in males affected by atherosclerosis of different vascular beds. Thirty-seven subjects affected by post-infarction cardiopathy (M.I.) showed significantly higher values of total-C, VLDL-C and LDL-C when compared to 52 controls. Twenty-three patients affected by non-occlusive ischaemic heart disease (I.H.D.) showed higher values than controls of total-C, VLCL-C, LDL-C, total TG, VLDL-TG, and GDL-TG. Twenty-three patients with atherosclerosis of the inferior limbs (P.A.) were characterized by increased levels of total-TG, VLDL-TG, VLDL-C, HDL-C. A group of patients who had suffered a stroke from cerebro-vascular disease (C.V.D.) did not show any significant difference from controls. In the M.I. group, 56% of the patients had a high level of C-VLDL. Patients with I.H.D. were characterized mostly by an increase in C-LDL, Patients with P.A. showed the highest values of total -TG, VLDL-TG and LDL-TG. Some of the observed differences are probably due to different metabolic backgrounds. Some other differences may be due to variations in dietary habits after heart infarction. Patients with levels of plasma cholesterol and triglyceride beyond the 90th percentile of the normal group showed many abnormalities in the chemical composition of their lipoproteins. It is noteworthy that increased amounts of cholesterol may collect in lipoprotein classes different from LDL while increased amounts of triglyceride may collect in classes different from VLDL."}
{"id": "PMID:189784", "title": "Lecithin: cholesterol acyl transfer rate in plasma and its relation to lipid and lipoprotein concentrations in primary hyperlipidemia.", "content": "Plasma lecithin: cholesterol acyl transfer (LCAT) rate and concentrations of lipids in plasma and lipoproteins were studied in 107 hyperlipidemic subjects. In all types of hyperlipoproteinemia LCAT rates were higher than in a normolipidemic reference group. LCAT rates were highest in type IV and V. There was a considerable overlap of LCAT rates between type IIa, IIb and reference subjects. The LCAT rate correlated positively with very low density lipoprotein concentration, body mass and excess body mass. Low density lipoprotein concentration correlated positively with the LCAT rate only in the reference group. The high density lipoprotein concentration correlated negatively with the LCAT rate. It was suggested that the LCAT rate in vitro reflects the in vivo turnover of cholesteryl esters as a part of the turnover of apoprotein-B containing lipoprotein complexes in plasma. The results might then indicate an inflow rate of lipoproteins in plasma that is increased in most type IV cases but normal or only moderately increased in type IIa and IIb subjects. Analysing the relations between the LCAT rate and the concentrations of lipids in plasma by multiple regression indicated hypothetically deficiencies of lipoprotein removal from plasma in half of type IIa and one third of type IIb subjects.", "contents": "Lecithin: cholesterol acyl transfer rate in plasma and its relation to lipid and lipoprotein concentrations in primary hyperlipidemia. Plasma lecithin: cholesterol acyl transfer (LCAT) rate and concentrations of lipids in plasma and lipoproteins were studied in 107 hyperlipidemic subjects. In all types of hyperlipoproteinemia LCAT rates were higher than in a normolipidemic reference group. LCAT rates were highest in type IV and V. There was a considerable overlap of LCAT rates between type IIa, IIb and reference subjects. The LCAT rate correlated positively with very low density lipoprotein concentration, body mass and excess body mass. Low density lipoprotein concentration correlated positively with the LCAT rate only in the reference group. The high density lipoprotein concentration correlated negatively with the LCAT rate. It was suggested that the LCAT rate in vitro reflects the in vivo turnover of cholesteryl esters as a part of the turnover of apoprotein-B containing lipoprotein complexes in plasma. The results might then indicate an inflow rate of lipoproteins in plasma that is increased in most type IV cases but normal or only moderately increased in type IIa and IIb subjects. Analysing the relations between the LCAT rate and the concentrations of lipids in plasma by multiple regression indicated hypothetically deficiencies of lipoprotein removal from plasma in half of type IIa and one third of type IIb subjects."}
{"id": "PMID:189786", "title": "Administration of antigen by intralymphatic route in the rat. II. Results in tumor active immunotherapy (delta). Preliminary report.", "content": "Tumor growth and survival time were followed in rats transplanted with Morris hepatoma 5123 and previously injected with a crude homogenate of the same tumor by the intradermic or intralymphatic route. Female rats treated by the intralymphatic route showed a longer survival time and impaired tumor growth. Male rats did not show any difference.", "contents": "Administration of antigen by intralymphatic route in the rat. II. Results in tumor active immunotherapy (delta). Preliminary report. Tumor growth and survival time were followed in rats transplanted with Morris hepatoma 5123 and previously injected with a crude homogenate of the same tumor by the intradermic or intralymphatic route. Female rats treated by the intralymphatic route showed a longer survival time and impaired tumor growth. Male rats did not show any difference."}
{"id": "PMID:189787", "title": "Virus-like antigen associated with hepatitis A: investigations in children's acute hepatitis.", "content": "Stool specimens, collected from 8 children with viral hepatitis [5 of type A, presumably, and 3 of type B (HBsAg-positive)] during the acute phase, were examined in the electron microscope. The presence of 27-nm virus-like particles, aggregated by the convalescent serum of a chimpanzee infected with MS-1 and not by the serum of the same animal drawn before infection, was detected by immune electron microscopy (IEM) in the stools of 3 out of the 5 children with suspected hepatitis A. The virus-like particles (HA-Ag) present in the stools were aggregated by the serum drawn from the corresponding subject during convalescence and not by that obtained in the acute phase of the disease. Employing as antigen a stool particle preparation purified by isopycnic banding in cesium cloride, it was pointed out that, in all 5 children with suspected hepatitis A, antibodies capable to cause the aggregation of HA-Ag particles, appeared. Anti-HA antibodies turned out to be present also in three lots of commercial immunoglobulins. In the three subjects with type B hepatitis (HBsAg-positive) neither virus-like particles with a 27-nm diameter were observed, nor anti-HA antibodies appeared in the convalescent serum.", "contents": "Virus-like antigen associated with hepatitis A: investigations in children's acute hepatitis. Stool specimens, collected from 8 children with viral hepatitis [5 of type A, presumably, and 3 of type B (HBsAg-positive)] during the acute phase, were examined in the electron microscope. The presence of 27-nm virus-like particles, aggregated by the convalescent serum of a chimpanzee infected with MS-1 and not by the serum of the same animal drawn before infection, was detected by immune electron microscopy (IEM) in the stools of 3 out of the 5 children with suspected hepatitis A. The virus-like particles (HA-Ag) present in the stools were aggregated by the serum drawn from the corresponding subject during convalescence and not by that obtained in the acute phase of the disease. Employing as antigen a stool particle preparation purified by isopycnic banding in cesium cloride, it was pointed out that, in all 5 children with suspected hepatitis A, antibodies capable to cause the aggregation of HA-Ag particles, appeared. Anti-HA antibodies turned out to be present also in three lots of commercial immunoglobulins. In the three subjects with type B hepatitis (HBsAg-positive) neither virus-like particles with a 27-nm diameter were observed, nor anti-HA antibodies appeared in the convalescent serum."}
{"id": "PMID:189788", "title": "Sero-epidemiological survey on human and swine influenza A. Situation at the onset of summer 1976.", "content": "A serological survey was performed to detect the presence of HI antibodies against the swine-like A/New Jersey/76 (Hsw1 N1) and the human A/Victoria 3/75 (H3N2) virus strains in the sera of 700 subjects of different age, and of 244 swine. HI antibodies against A/New Jersey/76 strain were not detected in 308 subjects younger than 31 years. They turned out to be present in 8% of the subjects from 31 to 43 years, always at low titre, and at a different titre, in 50% of the subjects from 44 to 58 years and in 90% of the subjects older than 58 years. None of the 244 swine tested from breeding farms of Liguria, Piedmont and Lombardy turned out to be endowed with antibodies against A/New Jersey/76 virus. This shows that the swine-like virus, which caused infections in the human population up to about 1930, did not circulate any more subsequently and that the swine also are now free from this infection. As far as the A/Victoria 3/75 strain is concerned, HI antibodies were detected in the different age groups with a frequency ranging between 41 and 69%. The fact that in many subjects antibodies were present at low titre suggests that their presence should be only partially brought back to infections caused by A/Victoria 3/75 but that in many cases it is the expression of a heterologous response to previous infections caused by other A H3N2 strains. HI antibodies against A/Victoria 3/75 were found also in 13% of the swine examined. A group of older people, who had been regularly immunized for years with the inactivated (A H3N2-B vaccine) showed an HI antibody titre significantly higher in comparison with subjects of equivalent age not vaccinated both against A/Victoria 3/75 and A/New Jersey/76.", "contents": "Sero-epidemiological survey on human and swine influenza A. Situation at the onset of summer 1976. A serological survey was performed to detect the presence of HI antibodies against the swine-like A/New Jersey/76 (Hsw1 N1) and the human A/Victoria 3/75 (H3N2) virus strains in the sera of 700 subjects of different age, and of 244 swine. HI antibodies against A/New Jersey/76 strain were not detected in 308 subjects younger than 31 years. They turned out to be present in 8% of the subjects from 31 to 43 years, always at low titre, and at a different titre, in 50% of the subjects from 44 to 58 years and in 90% of the subjects older than 58 years. None of the 244 swine tested from breeding farms of Liguria, Piedmont and Lombardy turned out to be endowed with antibodies against A/New Jersey/76 virus. This shows that the swine-like virus, which caused infections in the human population up to about 1930, did not circulate any more subsequently and that the swine also are now free from this infection. As far as the A/Victoria 3/75 strain is concerned, HI antibodies were detected in the different age groups with a frequency ranging between 41 and 69%. The fact that in many subjects antibodies were present at low titre suggests that their presence should be only partially brought back to infections caused by A/Victoria 3/75 but that in many cases it is the expression of a heterologous response to previous infections caused by other A H3N2 strains. HI antibodies against A/Victoria 3/75 were found also in 13% of the swine examined. A group of older people, who had been regularly immunized for years with the inactivated (A H3N2-B vaccine) showed an HI antibody titre significantly higher in comparison with subjects of equivalent age not vaccinated both against A/Victoria 3/75 and A/New Jersey/76."}
{"id": "PMID:189785", "title": "[Liver resection in children. Experience in 10 cases].", "content": "The authors report their experience with ten major hepatic resections; six on the right lobe and four on the left. Six of the resected masses were hepatoblastomas, two were hamartomas, was a hemangioma, and the last one a pheochromocytoma of the right adrenal gland with invasion to the liver next from the affected site. The four patients with major hepatic resection of the left lobe are at present alive, ranging from two months to two years after surgery. Of the six patients with major resection of the right lobe, three died during surgery, another one died late post-operatively and one died a year after surgery from generalized metastasis of an hepatoblastoma. The sixth patient is alive with no complications, four months after surgery. The authors used two types of hepatic resections and they make some recommendations for achieving better results in this type of operation.", "contents": "[Liver resection in children. Experience in 10 cases]. The authors report their experience with ten major hepatic resections; six on the right lobe and four on the left. Six of the resected masses were hepatoblastomas, two were hamartomas, was a hemangioma, and the last one a pheochromocytoma of the right adrenal gland with invasion to the liver next from the affected site. The four patients with major hepatic resection of the left lobe are at present alive, ranging from two months to two years after surgery. Of the six patients with major resection of the right lobe, three died during surgery, another one died late post-operatively and one died a year after surgery from generalized metastasis of an hepatoblastoma. The sixth patient is alive with no complications, four months after surgery. The authors used two types of hepatic resections and they make some recommendations for achieving better results in this type of operation."}
{"id": "PMID:189791", "title": "Ultrastructure of abnormal membrane inclusions in nuclei of human myocardial cells.", "content": "The ultrastructure of the nuclear envelope was studied in cardiac muscle cells of 12 patients undergoing cardiopulmonary bypass surgery. Two main types of membrane inclusions, globular and tubular, were observed in the nuclei. The globular type was found in 6 patients. The globular inclusions were about 0-5mu to 1-5mu in diameter and lined by two unit membranes equal in structure to that of the nuclear envelope. The lining was probably always in continuity with the nuclear membranes. Such inclusions contained a granular matrix in which no cytoplasmic organelles could be seen, with the exception of a limited number of ribosomes. The tubular type of nuclear inclusion was observed in the cardiac tissue of 3 patients. These tubules ran in straight or slightly bent segments of about 0-2 mu to 1-6 mu length, interrupted by bendings at obtuse or right angles. The diameter of their lumina measured about 300 A to 800 A. Such tubules were nearly always found in areas of the nucleoplasm rich in heterochromatin. Nuclear pore-like structures were occasionally found in the tubular wall. The tubular wall consisted of a single unit membrane shown to be in continuity with the inner membrane of the nuclear envelope. Since these nuclear aberrances have been observed at all of the stages examined, the possibility is considered that they may represent a specific nuclear response to the process of cardiac hypertrophy.", "contents": "Ultrastructure of abnormal membrane inclusions in nuclei of human myocardial cells. The ultrastructure of the nuclear envelope was studied in cardiac muscle cells of 12 patients undergoing cardiopulmonary bypass surgery. Two main types of membrane inclusions, globular and tubular, were observed in the nuclei. The globular type was found in 6 patients. The globular inclusions were about 0-5mu to 1-5mu in diameter and lined by two unit membranes equal in structure to that of the nuclear envelope. The lining was probably always in continuity with the nuclear membranes. Such inclusions contained a granular matrix in which no cytoplasmic organelles could be seen, with the exception of a limited number of ribosomes. The tubular type of nuclear inclusion was observed in the cardiac tissue of 3 patients. These tubules ran in straight or slightly bent segments of about 0-2 mu to 1-6 mu length, interrupted by bendings at obtuse or right angles. The diameter of their lumina measured about 300 A to 800 A. Such tubules were nearly always found in areas of the nucleoplasm rich in heterochromatin. Nuclear pore-like structures were occasionally found in the tubular wall. The tubular wall consisted of a single unit membrane shown to be in continuity with the inner membrane of the nuclear envelope. Since these nuclear aberrances have been observed at all of the stages examined, the possibility is considered that they may represent a specific nuclear response to the process of cardiac hypertrophy."}
{"id": "PMID:189792", "title": "Effect of pretreatment with immune serum on murine sarcoma virus (Moloney) tumour induction and growth.", "content": "Regressor serum from MSV-M-infected mice markedly reduced MSV-M oncogenesis when administered i.p. (0-1 ml/mouse) as much as 30 days before i.m. MSV-M infection in adult BALB/c mice. The regressor serum activity appeared to be directly dependent on the amount of IgG, as shown by: (1) inactivity of sera which have low virus-neutralizing antibody content; (2) high effectiveness only of the IgG serum fraction; (3) inactivity of regressor serum incubated with anti-mouse gamma-globulin serum. The regressor serum activity was specific and could not be ascribed to interferon or interferon-inducing factors, antigen-antibody complexes or free antigen. The activity was not suppressed by sublethal irradiation (380 rad) of recipient mice. These results suggest that the activity of regressor serum administered before MSV-M infection is mediated through sensitization of host cells which are not radiosensitive.", "contents": "Effect of pretreatment with immune serum on murine sarcoma virus (Moloney) tumour induction and growth. Regressor serum from MSV-M-infected mice markedly reduced MSV-M oncogenesis when administered i.p. (0-1 ml/mouse) as much as 30 days before i.m. MSV-M infection in adult BALB/c mice. The regressor serum activity appeared to be directly dependent on the amount of IgG, as shown by: (1) inactivity of sera which have low virus-neutralizing antibody content; (2) high effectiveness only of the IgG serum fraction; (3) inactivity of regressor serum incubated with anti-mouse gamma-globulin serum. The regressor serum activity was specific and could not be ascribed to interferon or interferon-inducing factors, antigen-antibody complexes or free antigen. The activity was not suppressed by sublethal irradiation (380 rad) of recipient mice. These results suggest that the activity of regressor serum administered before MSV-M infection is mediated through sensitization of host cells which are not radiosensitive."}
{"id": "PMID:189793", "title": "Lung cancer in Hong Kong Chinese: mortality and histological types, 1960-1972.", "content": "Age-adjusted mortality from lung cancer rose rapidly in both males and females in Hong Kong from 1960-1972. The relative frequency of epidermoid carcinoma increased in male bronchial biopsies but not in lung biopsies, resections, or autopsies; there was a decline in small-cell anaplastic carcinoma. In both males and females the ratio of Kreyberg Group I (epidermoid and small-cell anaplastic) to Group II (adenocarcinoma and carcinoid) tumours did not increase, despite an 80% rise in mortality from lung cancer. Adenocarcinoma was the most common type in females, despite the high mortality from lung cancer. It is speculated that cigarette smoking might produce a different pattern of histological types among Hong Kong Chinese, or that additional aetiological factors may be operating there.", "contents": "Lung cancer in Hong Kong Chinese: mortality and histological types, 1960-1972. Age-adjusted mortality from lung cancer rose rapidly in both males and females in Hong Kong from 1960-1972. The relative frequency of epidermoid carcinoma increased in male bronchial biopsies but not in lung biopsies, resections, or autopsies; there was a decline in small-cell anaplastic carcinoma. In both males and females the ratio of Kreyberg Group I (epidermoid and small-cell anaplastic) to Group II (adenocarcinoma and carcinoid) tumours did not increase, despite an 80% rise in mortality from lung cancer. Adenocarcinoma was the most common type in females, despite the high mortality from lung cancer. It is speculated that cigarette smoking might produce a different pattern of histological types among Hong Kong Chinese, or that additional aetiological factors may be operating there."}
{"id": "PMID:189794", "title": "Histochemical and histological effects of lead on the liver and kidney of the dog.", "content": "In a series of 3 experiments, beagle dogs were dosed orally with lead carbonate and the histochemical and histological changes in the liver and kidney assessed. Dosing at 50 mg/kg per day for 5 weeks resulted in well documented histological changes in the kidney and hydropic degeneration in the liver; significant alterations in the activity of the majority of enzymes studied were also seen in both organs. In dogs dosed for one week at 50 or 100 mg/kg no histological changes were seen and histochemical alterations were mainly confined to the dehydrogenases and NADPH diaphorase. A third group of dogs were dosed for 3 weeks; during a subsequent recovery period of almost 2 months the mild clinical effects produced by lead during the dosing period were quickly reversible except in 2 dogs. At the end of the recovery period histochemical alterations were evident in both organs of these 2 dogs principally shown by a reduction in the dehydrogenases of the liver. The findings are interpreted as an effect by lead on a range of cellular enzymes particularly those involved in energy production, these effects being still demonstrable after an extended recovery period.", "contents": "Histochemical and histological effects of lead on the liver and kidney of the dog. In a series of 3 experiments, beagle dogs were dosed orally with lead carbonate and the histochemical and histological changes in the liver and kidney assessed. Dosing at 50 mg/kg per day for 5 weeks resulted in well documented histological changes in the kidney and hydropic degeneration in the liver; significant alterations in the activity of the majority of enzymes studied were also seen in both organs. In dogs dosed for one week at 50 or 100 mg/kg no histological changes were seen and histochemical alterations were mainly confined to the dehydrogenases and NADPH diaphorase. A third group of dogs were dosed for 3 weeks; during a subsequent recovery period of almost 2 months the mild clinical effects produced by lead during the dosing period were quickly reversible except in 2 dogs. At the end of the recovery period histochemical alterations were evident in both organs of these 2 dogs principally shown by a reduction in the dehydrogenases of the liver. The findings are interpreted as an effect by lead on a range of cellular enzymes particularly those involved in energy production, these effects being still demonstrable after an extended recovery period."}
{"id": "PMID:189795", "title": "Magnetic resonance and kinetic studies of the role of the divalent cation activator of RNA polymerase from Escherichia coli.", "content": "The interaction of Mn2+, substrates and initiators with RNA polymerase have been studied by kinetic and magnetic resonance methods. As determined by electron paramagnetic resonance, Mn2+ binds to RNA polymerase at one tight binding site with a dissociation constant less than 10 muM and at 6 +/- 1 weak binding sites with dissociation constants 100-fold greater. The binding of Mn2+ to RNA polymerase at both types of sites causes an order of magnitude enhancement of the paramagnetic effect of Mn2+ on the longitudinal relaxation rate of water protons, indicating the presence of residual water ligands on the enzyme-bound Mn2+. A kinetic analysis of the Mn2+-activated enzyme with poly(dT) as template indicates the substrate to be MnATP under steady-state conditions in the presence or absence of the initiator ApA. ATP and UTP interact with the tightly bound Mn2+ to form ternary complexes with approximately 50% greater enhancement factors. The dissociation constant of MnATP from the tight Mn2+ site as determined by longitudinal proton relaxation rate (PRR) titration (4.7 muM) is similar to the KM of MnATP in the ApA-initiated RNA polymerase reaction (10 +/- 3 muM) but not in the ATP-initiated reaction (160 +/- 30 muM). Similarly, the dissociation constant of the substrate MnUTP from the tight Mn2+ site (90 muM) is in agreement with the KM of MnUTP (101 +/- 13 muM) when poly[d(A-T)]-poly[d(A-T)] is used as template, indicating the tight Mn2+ site to be the catalytic site for RNA chain elongation. Manganese adenylyl imidodiphosphate (MnAMP-PNP) has been found to be a substrate for RNA polymerase. It has the same affinity as MnATP for the tight site but, unlike the results obtained with MnATP, the enhancement is decreased by 43% in the enzyme Mn-AMP-PNP complex. These results suggest that the enzyme-bound Mn2+ interacts with the leaving pyrophosphate group. The initiators ApA and ApU and the inhibitor rifamycin interact with the enzyme-Mn2+ complex producing small (15-20%) decreases in the enhancement. The dissociation constant of ApA estimated from PRR data (less than or equal to 1.5 muM) agrees with that determined kinetically (1.0 +/- 0.5 muM) as the concentration of ApA required to produce half-maximal change in the KM of MnATP. In the presence of the initiation specific reagents ApA, ApU, or rifamycin, the affinity of the enzyme-Mn complex for ATP or UTP shows little change. However, ATP and UTP no longer increase the enhancement factor of the tightly bound Mn2+ but decrease it by 30-55%, indicating a change in the environment of the Mn2+-substrate complex on the enzyme when the initiation site is either occupied or blocked. Although the role of the six weak Mn2+ binding sites is not clear, the presence of a single tightly bound Mn2+ at the catalytic site for chain elongation which interacts with the substrate reinforces the number of active sites as one per molecule of holoenzyme and provides a paramagnetic reference point for further structural studies.", "contents": "Magnetic resonance and kinetic studies of the role of the divalent cation activator of RNA polymerase from Escherichia coli. The interaction of Mn2+, substrates and initiators with RNA polymerase have been studied by kinetic and magnetic resonance methods. As determined by electron paramagnetic resonance, Mn2+ binds to RNA polymerase at one tight binding site with a dissociation constant less than 10 muM and at 6 +/- 1 weak binding sites with dissociation constants 100-fold greater. The binding of Mn2+ to RNA polymerase at both types of sites causes an order of magnitude enhancement of the paramagnetic effect of Mn2+ on the longitudinal relaxation rate of water protons, indicating the presence of residual water ligands on the enzyme-bound Mn2+. A kinetic analysis of the Mn2+-activated enzyme with poly(dT) as template indicates the substrate to be MnATP under steady-state conditions in the presence or absence of the initiator ApA. ATP and UTP interact with the tightly bound Mn2+ to form ternary complexes with approximately 50% greater enhancement factors. The dissociation constant of MnATP from the tight Mn2+ site as determined by longitudinal proton relaxation rate (PRR) titration (4.7 muM) is similar to the KM of MnATP in the ApA-initiated RNA polymerase reaction (10 +/- 3 muM) but not in the ATP-initiated reaction (160 +/- 30 muM). Similarly, the dissociation constant of the substrate MnUTP from the tight Mn2+ site (90 muM) is in agreement with the KM of MnUTP (101 +/- 13 muM) when poly[d(A-T)]-poly[d(A-T)] is used as template, indicating the tight Mn2+ site to be the catalytic site for RNA chain elongation. Manganese adenylyl imidodiphosphate (MnAMP-PNP) has been found to be a substrate for RNA polymerase. It has the same affinity as MnATP for the tight site but, unlike the results obtained with MnATP, the enhancement is decreased by 43% in the enzyme Mn-AMP-PNP complex. These results suggest that the enzyme-bound Mn2+ interacts with the leaving pyrophosphate group. The initiators ApA and ApU and the inhibitor rifamycin interact with the enzyme-Mn2+ complex producing small (15-20%) decreases in the enhancement. The dissociation constant of ApA estimated from PRR data (less than or equal to 1.5 muM) agrees with that determined kinetically (1.0 +/- 0.5 muM) as the concentration of ApA required to produce half-maximal change in the KM of MnATP. In the presence of the initiation specific reagents ApA, ApU, or rifamycin, the affinity of the enzyme-Mn complex for ATP or UTP shows little change. However, ATP and UTP no longer increase the enhancement factor of the tightly bound Mn2+ but decrease it by 30-55%, indicating a change in the environment of the Mn2+-substrate complex on the enzyme when the initiation site is either occupied or blocked. Although the role of the six weak Mn2+ binding sites is not clear, the presence of a single tightly bound Mn2+ at the catalytic site for chain elongation which interacts with the substrate reinforces the number of active sites as one per molecule of holoenzyme and provides a paramagnetic reference point for further structural studies."}
{"id": "PMID:189796", "title": "Fluorescence and nucleotide binding properties of Escherichia coli uridine diphosphate galactose 4-epimerase: support for a model for nonstereospedific action.", "content": "The fluorescence emission spectrum for reduced diphosphopyridine nucleotide (DPNH) in Escherichia coli uridine diphosphate galactose 4-epimerase-DPNH complexes has a maximum at 435 nm, which is about twice as intense when the excitation is at 280 nm as at 340 nm. The fluorescence excitation spectrum monitored at 460 nm has two maxima, one at 340-345 nm and another about twice as intense at 280 nm. The polarization of DPNH fluorescence by these complexes is 0.43-0.44 compared with 0.46 for DPNH immobilized in propylene glycol at -20 degrees C. The small degree of fluorescence depolarization is due to rotational relaxation of the protein, relaxation time 205 ns. The excited-state lifetimes in epimerase-DPNH-nucleotide complexes are 3.5-4.2 ns. The fluorescence data show that the dihydropyridine ring in these complexes is highly immobilized and exhibits no detectable independent motion relative to rotational motions of the protein. The inhibition constants for uridine monophosphate (UMP) and 2,2,6,6-tetramethyl-4-piperidinyl-1-oxyl uridyl pyrophosphate acting as competitive reversible inhibitors of epimerase-DPN+ are 1.2 and 0.2 mM, respectively, at 27 degrees C in 0.1 M sodium bicinate buffer at pH 8.5. A collection of Ki and Km values for uridine nucleotide inhibitors and substrates indicates that the principle substrate binding interactions involve the nucleotide moieties of substrates. Dissociation constants for uridine nucleotides dissociating from epimerase-DPNH-nucleotide complexes, measured by ultraviolet absorption and fluorescence techniques, are 12 muM for UMP, 14 muM for UDP-hexopyranoses, 4 muM for UDP-pentopyranoses, 27 muM for p-bromoacetamidophenyl uridyl pyrophosphate, 0.14 muM for UDP-4-ketohexopyranose intermediate, and 0.36 muM for UDP-4-ketopentopyranose intermediate at 27 degrees C in 0.1 M sodium bicinate buffer at pH 8.5. Analysis of these data shows conclusively that the major part of the binding free energy for UDP-4-ketopyranose intermediates binding to epimerase-DPNH is attributable to the uridylpyrophosphoryl components and that the glycosyl-binding free energies are much smaller. The data show that the action of this enzyme does not require tight binding between the active site and glycosyl groups of either substrates or intermediates, although there is favorable binding of the uridylpyrophosphoryl components, particularly by epimerase-DPNH. It is postulated that nonstereospecific action results from and depends upon relatively weak, nonspecific active site binding of glycosyl groups in substrates and intermediates and that the uridylpyrophosphoryl groups serve as binding anchors in the epimerization process.", "contents": "Fluorescence and nucleotide binding properties of Escherichia coli uridine diphosphate galactose 4-epimerase: support for a model for nonstereospedific action. The fluorescence emission spectrum for reduced diphosphopyridine nucleotide (DPNH) in Escherichia coli uridine diphosphate galactose 4-epimerase-DPNH complexes has a maximum at 435 nm, which is about twice as intense when the excitation is at 280 nm as at 340 nm. The fluorescence excitation spectrum monitored at 460 nm has two maxima, one at 340-345 nm and another about twice as intense at 280 nm. The polarization of DPNH fluorescence by these complexes is 0.43-0.44 compared with 0.46 for DPNH immobilized in propylene glycol at -20 degrees C. The small degree of fluorescence depolarization is due to rotational relaxation of the protein, relaxation time 205 ns. The excited-state lifetimes in epimerase-DPNH-nucleotide complexes are 3.5-4.2 ns. The fluorescence data show that the dihydropyridine ring in these complexes is highly immobilized and exhibits no detectable independent motion relative to rotational motions of the protein. The inhibition constants for uridine monophosphate (UMP) and 2,2,6,6-tetramethyl-4-piperidinyl-1-oxyl uridyl pyrophosphate acting as competitive reversible inhibitors of epimerase-DPN+ are 1.2 and 0.2 mM, respectively, at 27 degrees C in 0.1 M sodium bicinate buffer at pH 8.5. A collection of Ki and Km values for uridine nucleotide inhibitors and substrates indicates that the principle substrate binding interactions involve the nucleotide moieties of substrates. Dissociation constants for uridine nucleotides dissociating from epimerase-DPNH-nucleotide complexes, measured by ultraviolet absorption and fluorescence techniques, are 12 muM for UMP, 14 muM for UDP-hexopyranoses, 4 muM for UDP-pentopyranoses, 27 muM for p-bromoacetamidophenyl uridyl pyrophosphate, 0.14 muM for UDP-4-ketohexopyranose intermediate, and 0.36 muM for UDP-4-ketopentopyranose intermediate at 27 degrees C in 0.1 M sodium bicinate buffer at pH 8.5. Analysis of these data shows conclusively that the major part of the binding free energy for UDP-4-ketopyranose intermediates binding to epimerase-DPNH is attributable to the uridylpyrophosphoryl components and that the glycosyl-binding free energies are much smaller. The data show that the action of this enzyme does not require tight binding between the active site and glycosyl groups of either substrates or intermediates, although there is favorable binding of the uridylpyrophosphoryl components, particularly by epimerase-DPNH. It is postulated that nonstereospecific action results from and depends upon relatively weak, nonspecific active site binding of glycosyl groups in substrates and intermediates and that the uridylpyrophosphoryl groups serve as binding anchors in the epimerization process."}
{"id": "PMID:189797", "title": "A study of conformational changes in two beta-93 modified hemoglobin A's using a triphosphate spin label.", "content": "The binding of oxygen and 1-oxyl-2,2,6,6-tetramethylpiperidine 4-triphosphate (spin-labeled triphosphate) to normal adult human hemoglobin (HbA) covalently labeled at the beta-93 sulfhydryl groups with N-(2,2,6,6-tetramethyl-4-piperidinyl)iodoacetamide (I) was studied. HbA-I was used as a model for HbA labeled at the beta-93 SH groups with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)iodoacetamide (II) since the binding of SLTP to HbA-II could not be measured conveniently, in the presence of the paramagnetic resonance signal of II. Both HbA-I and HbA-II can be treated as variant hemoglobins with abnormal beta chains. The oxygen and SLTP binding data from HbA-I and oxygen binding data from HbA-II are consistent with a concerted transition model for cooperativity which assumes nonequivalence between alpha and beta subunits (GCT model). The distribution of environments \"seen\" by conformation sensitive probes such as II and trifluoracetone (19F NMR probe) attached to the beta-93 sulfhydryl groups of HbA can also be accounted for by the GCT model. It is proposed that the beta-93 probes sense the dramatic change in beta subunit structure resulting from the quaternary structure change (T leads to R) upon heme saturation as well as tertiary structure changes at the alpha1-beta2 contact region resulting from ligand binding to the beta-heme group. Structural changes caused by ligation of the alpha-hemes are not discussed.", "contents": "A study of conformational changes in two beta-93 modified hemoglobin A's using a triphosphate spin label. The binding of oxygen and 1-oxyl-2,2,6,6-tetramethylpiperidine 4-triphosphate (spin-labeled triphosphate) to normal adult human hemoglobin (HbA) covalently labeled at the beta-93 sulfhydryl groups with N-(2,2,6,6-tetramethyl-4-piperidinyl)iodoacetamide (I) was studied. HbA-I was used as a model for HbA labeled at the beta-93 SH groups with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)iodoacetamide (II) since the binding of SLTP to HbA-II could not be measured conveniently, in the presence of the paramagnetic resonance signal of II. Both HbA-I and HbA-II can be treated as variant hemoglobins with abnormal beta chains. The oxygen and SLTP binding data from HbA-I and oxygen binding data from HbA-II are consistent with a concerted transition model for cooperativity which assumes nonequivalence between alpha and beta subunits (GCT model). The distribution of environments \"seen\" by conformation sensitive probes such as II and trifluoracetone (19F NMR probe) attached to the beta-93 sulfhydryl groups of HbA can also be accounted for by the GCT model. It is proposed that the beta-93 probes sense the dramatic change in beta subunit structure resulting from the quaternary structure change (T leads to R) upon heme saturation as well as tertiary structure changes at the alpha1-beta2 contact region resulting from ligand binding to the beta-heme group. Structural changes caused by ligation of the alpha-hemes are not discussed."}
{"id": "PMID:189798", "title": "Interaction of detergents with cytochrome c oxidase.", "content": "The binding of ionic and nonionic, nondenaturing detergents to cytochrome c oxidase has been examined. All bind and displace part but not all of the phospholipid that is associated with the enzyme after isolation. From 6 to 10 phospholipid molecules, depending on the detergent used, do not exchange and these are mostly diphosphatidylglycerol molecules as first shown by Awasthi et al. ((1971) Biochim. Biophys. Acta 226, 42). The binding of Triton X-100 and deoxycholate to the cytochrome c oxidase complex has been studied in detail. Both bind to the enzyme above their critical micelle concentrations: Triton X-100 in the amount of 180 +/- 10 molecules per complex and deoxycholate in the amount of 80 +/- 4 molecules per complex. In nonionic detergents, cytochrome c oxidase exists as a dimer (4 heme complex). The enzyme is dissociated into the monomer or heme aa3 complex by delipidation in bile salts. Activity measurements in different detergents suggest that cytochrome c oxidase requires a flexible, hydrophobic environment for maximal activity and that the dimer or 4 heme complex may be the active species.", "contents": "Interaction of detergents with cytochrome c oxidase. The binding of ionic and nonionic, nondenaturing detergents to cytochrome c oxidase has been examined. All bind and displace part but not all of the phospholipid that is associated with the enzyme after isolation. From 6 to 10 phospholipid molecules, depending on the detergent used, do not exchange and these are mostly diphosphatidylglycerol molecules as first shown by Awasthi et al. ((1971) Biochim. Biophys. Acta 226, 42). The binding of Triton X-100 and deoxycholate to the cytochrome c oxidase complex has been studied in detail. Both bind to the enzyme above their critical micelle concentrations: Triton X-100 in the amount of 180 +/- 10 molecules per complex and deoxycholate in the amount of 80 +/- 4 molecules per complex. In nonionic detergents, cytochrome c oxidase exists as a dimer (4 heme complex). The enzyme is dissociated into the monomer or heme aa3 complex by delipidation in bile salts. Activity measurements in different detergents suggest that cytochrome c oxidase requires a flexible, hydrophobic environment for maximal activity and that the dimer or 4 heme complex may be the active species."}
{"id": "PMID:189799", "title": "Thermodynamic limits on the size and size distribution of nucleic acids synthesized in vitro: the role of pyrophosphate hydrolysis.", "content": "The free-energy change of phosphodiester bond formation from nucleoside triphosphates is more favorable than with nucleoside diphosphates as substrates. Base-stacking interactions can make significant contributions to both delta G degrees ' values. Pyrophosphate hydrolysis when it accompanies the former reaction dominates all thermodynamic considerations. Three experimental situations are discussed in which high-molecular-weight polynucleotides are synthesized without a strong driving force for covalent bond formation. For one of these, a kinetic scheme is presented which encompasses an early narrow Poisson distribution of chain lengths with ultimate passage to a disperse equilibrium population of chain sizes. Hydrolytic removal of pyrophosphate expands the time scale for this undesirable process by a factor of 10(9), while it enormously elevates the thermodynamic ceiling for the average degrees of polymerization in the other two examples. The electron micrographically revealed broad size population from an early study of partial replication of a T7 DNA template is found to adhere (fortuitously) to a disperse most probable representation. Some possible origins are examined for the branched structures in this product, as well as in a later investigation of replication of this nucleic acid. The achievement of both very high molecular weights and sharply peaked size distributions in polynucleotides synthesized in vitro will require coupling to inorganic pyrophosphatase action as in vivo.", "contents": "Thermodynamic limits on the size and size distribution of nucleic acids synthesized in vitro: the role of pyrophosphate hydrolysis. The free-energy change of phosphodiester bond formation from nucleoside triphosphates is more favorable than with nucleoside diphosphates as substrates. Base-stacking interactions can make significant contributions to both delta G degrees ' values. Pyrophosphate hydrolysis when it accompanies the former reaction dominates all thermodynamic considerations. Three experimental situations are discussed in which high-molecular-weight polynucleotides are synthesized without a strong driving force for covalent bond formation. For one of these, a kinetic scheme is presented which encompasses an early narrow Poisson distribution of chain lengths with ultimate passage to a disperse equilibrium population of chain sizes. Hydrolytic removal of pyrophosphate expands the time scale for this undesirable process by a factor of 10(9), while it enormously elevates the thermodynamic ceiling for the average degrees of polymerization in the other two examples. The electron micrographically revealed broad size population from an early study of partial replication of a T7 DNA template is found to adhere (fortuitously) to a disperse most probable representation. Some possible origins are examined for the branched structures in this product, as well as in a later investigation of replication of this nucleic acid. The achievement of both very high molecular weights and sharply peaked size distributions in polynucleotides synthesized in vitro will require coupling to inorganic pyrophosphatase action as in vivo."}
{"id": "PMID:189800", "title": "Sequence specificity of internal methylation in B77 avian sarcoma virus RNA subunits.", "content": "Following ribonuclease digestion of methyl-3H-labeled B77 avian sarcoma virus RNA subunits, methylated oligonucleotides were isolated by diethylaminoethylcellulose chromotogrpahy. Partial nucleotide sequences were deduced from the known enzymatic specificities of the ribonucleases. In addition to methylated nucleosides in the 5'-terminal cap structure, m7G(5')GmpCp, N6-methyladenosine(m6A) was found to be present in only two internal sequences of the RNA molecule, Gpm6ApC and Apm6ApC. The average numbers of methylated nucleosides per RNA subunit are about 12-13 in Gpm6ApC, 1-2 in Apm6ApC, and 2 in m7GpppGmpCp. The sequences containing m6A in B77 sarcoma virus RNA are identical to m6A-containing sequences previously reported for the bulk mRNA from HeLa cells (Wei, C.M., Gershowitz, A., and Moss, B. (1976), Biochemistry 15, 397-401). Analysis of the oligonucleotides produced by RNase A digestion indicated that the sequence of bases on the 5' side of these trinucleotides is not specific. The oligonucleotide profile, however, was highly reproducible in different virus preparations. This suggests that the methylations occur at specific positions on the RNA molecule. Some of the methylated oligonucleotides produced by RNase A digestion appear to be present in less than molar amounts. Several hypotheses are proposed to explain this result.", "contents": "Sequence specificity of internal methylation in B77 avian sarcoma virus RNA subunits. Following ribonuclease digestion of methyl-3H-labeled B77 avian sarcoma virus RNA subunits, methylated oligonucleotides were isolated by diethylaminoethylcellulose chromotogrpahy. Partial nucleotide sequences were deduced from the known enzymatic specificities of the ribonucleases. In addition to methylated nucleosides in the 5'-terminal cap structure, m7G(5')GmpCp, N6-methyladenosine(m6A) was found to be present in only two internal sequences of the RNA molecule, Gpm6ApC and Apm6ApC. The average numbers of methylated nucleosides per RNA subunit are about 12-13 in Gpm6ApC, 1-2 in Apm6ApC, and 2 in m7GpppGmpCp. The sequences containing m6A in B77 sarcoma virus RNA are identical to m6A-containing sequences previously reported for the bulk mRNA from HeLa cells (Wei, C.M., Gershowitz, A., and Moss, B. (1976), Biochemistry 15, 397-401). Analysis of the oligonucleotides produced by RNase A digestion indicated that the sequence of bases on the 5' side of these trinucleotides is not specific. The oligonucleotide profile, however, was highly reproducible in different virus preparations. This suggests that the methylations occur at specific positions on the RNA molecule. Some of the methylated oligonucleotides produced by RNase A digestion appear to be present in less than molar amounts. Several hypotheses are proposed to explain this result."}
{"id": "PMID:189801", "title": "Characterization of DNA strand breakage in vitro by the antitumor protein neocarzinostatin.", "content": "The antitumor protein antibiotic neocarzinostatin causes strand scission of DNA in vitro in the presence of a sulfhydryl compound. The breaks are single stranded in nature and bear 5'-phosphoryl termini. All four deoxymononucleotides are recoverable at the 5'-ends of the cleavage sites although a higher proportion of dGMP and TMP are consistently found. The lesions are not repairable with polynucleotide ligase from Escherichia coli. A quantitative assay was developed to determine the pH profile and time course of the reaction. Data from protection experiments with synthetic and natural DNAs indicate the requirement for thymidylic acid and deoxyadenylic acid in the DNA for cutting. In DNA-RNA hybrids, riboadenylic acid can substitute for deoxyadenylic acid, whereas ribouridylic acid cannot substitute for thymidylic acid. Release of thymine is detected, and the amount of release correlates well with the number of strand scissions.", "contents": "Characterization of DNA strand breakage in vitro by the antitumor protein neocarzinostatin. The antitumor protein antibiotic neocarzinostatin causes strand scission of DNA in vitro in the presence of a sulfhydryl compound. The breaks are single stranded in nature and bear 5'-phosphoryl termini. All four deoxymononucleotides are recoverable at the 5'-ends of the cleavage sites although a higher proportion of dGMP and TMP are consistently found. The lesions are not repairable with polynucleotide ligase from Escherichia coli. A quantitative assay was developed to determine the pH profile and time course of the reaction. Data from protection experiments with synthetic and natural DNAs indicate the requirement for thymidylic acid and deoxyadenylic acid in the DNA for cutting. In DNA-RNA hybrids, riboadenylic acid can substitute for deoxyadenylic acid, whereas ribouridylic acid cannot substitute for thymidylic acid. Release of thymine is detected, and the amount of release correlates well with the number of strand scissions."}
{"id": "PMID:189802", "title": "Synthesis and template-directed polymerization of adenylyl(3'-5')adenosine cyclic 2', 3'-phosphate.", "content": "Adenylyl(3'-5')adenosine cyclic 2',3'-phosphate (A-A greater than p) was synthesized and its polymerization was attempted under various conditions inthe presence of poly(uridylic acid) and1,3-propanediamine. Reaction at -20 degrees C for 16 days gave polymerized products (up to the 8-mer) in 15% yield and was proved to be dependent on the template. Reaction at 0 degrees C for 16 days gave more extensive (up to the 10-mer) and more efficient (35%) polymerization. The newly formed phosphodiester linkage was exclusively 2'-5'. These results are discussed in comparison with the monomer-condensation reaction.", "contents": "Synthesis and template-directed polymerization of adenylyl(3'-5')adenosine cyclic 2', 3'-phosphate. Adenylyl(3'-5')adenosine cyclic 2',3'-phosphate (A-A greater than p) was synthesized and its polymerization was attempted under various conditions inthe presence of poly(uridylic acid) and1,3-propanediamine. Reaction at -20 degrees C for 16 days gave polymerized products (up to the 8-mer) in 15% yield and was proved to be dependent on the template. Reaction at 0 degrees C for 16 days gave more extensive (up to the 10-mer) and more efficient (35%) polymerization. The newly formed phosphodiester linkage was exclusively 2'-5'. These results are discussed in comparison with the monomer-condensation reaction."}
{"id": "PMID:189803", "title": "Poly(adenosine diphosphate-ribose) polymerase: the distribution of a chromosome-associated enzyme within the chromatin substructure.", "content": "The distribution of a chromatin-bound, nuclear protein modifying enzyme, poly (adenosine diphosphate-ribose) polymerase, and its product, poly(ADP-ribose), among various fractions of sheared and nuclease-digested HeLa cell chromatin has been examined. Epichlorohydrin-tris(hydroxymethyl)aminomethane-cellulose and glycerol gradient fractionation of solubilized chromatin indicated that poly(ADP-ribose)polymerase activity was associated primarily with the template active regions (euchromatin), whereas the transcriptionally inert chromatin fractions were found to contain relatively low levels of ADP-ribosylating activity. When isolated HeLa cell nuclei were digested in situ with micrococcal nuclease and the resultant chromatin was fractionated into nucleosome monomers (v bodies) and oligomers by sucrose gradient centrifugation, only material sedimenting faster than the 11S monomers was found to contain appreciable poly(ADP-ribose) polymerase activity. If, on the other hand, isolated HeLa cell nuclei were first incubated with labeled NAD, the substrate for poly(ADP-ribose) polymerase, prior to the preparation and fractionation of nuclease-digested chromatin, it was found that those chromatin fractions which possess significant poly(ADP-ribose) polymerase activity (nucleosome oligomers) are relatively deficient in the labeled product of this enzyme, and that a considerable portion of the homopolymeric product is ultimately associated with the 11S v bodies. Additional evidence is presented which indicates that the absence of nucleosome monomer-associated poly(ADP-ribose) polymerase activity is not due to the absence of a suitable acceptor on these structures, and that the activity of this enzyme within the chromatin is most probably dependent upon the physical integrity of the oligomeric structures themselves.", "contents": "Poly(adenosine diphosphate-ribose) polymerase: the distribution of a chromosome-associated enzyme within the chromatin substructure. The distribution of a chromatin-bound, nuclear protein modifying enzyme, poly (adenosine diphosphate-ribose) polymerase, and its product, poly(ADP-ribose), among various fractions of sheared and nuclease-digested HeLa cell chromatin has been examined. Epichlorohydrin-tris(hydroxymethyl)aminomethane-cellulose and glycerol gradient fractionation of solubilized chromatin indicated that poly(ADP-ribose)polymerase activity was associated primarily with the template active regions (euchromatin), whereas the transcriptionally inert chromatin fractions were found to contain relatively low levels of ADP-ribosylating activity. When isolated HeLa cell nuclei were digested in situ with micrococcal nuclease and the resultant chromatin was fractionated into nucleosome monomers (v bodies) and oligomers by sucrose gradient centrifugation, only material sedimenting faster than the 11S monomers was found to contain appreciable poly(ADP-ribose) polymerase activity. If, on the other hand, isolated HeLa cell nuclei were first incubated with labeled NAD, the substrate for poly(ADP-ribose) polymerase, prior to the preparation and fractionation of nuclease-digested chromatin, it was found that those chromatin fractions which possess significant poly(ADP-ribose) polymerase activity (nucleosome oligomers) are relatively deficient in the labeled product of this enzyme, and that a considerable portion of the homopolymeric product is ultimately associated with the 11S v bodies. Additional evidence is presented which indicates that the absence of nucleosome monomer-associated poly(ADP-ribose) polymerase activity is not due to the absence of a suitable acceptor on these structures, and that the activity of this enzyme within the chromatin is most probably dependent upon the physical integrity of the oligomeric structures themselves."}
{"id": "PMID:189804", "title": "Different metal-binding properties of the two sites of human transferrin.", "content": "Transferrin, the serum serum iron-transport protein which can bind two metal ions at physiologic pH, binds just one Fe3+, VO2+, or Cr3+ ion at pH 6.0. Fe3+ and VO2+ appear to be bound at the same site, designated A, based on electron paramagnetic resonance (EPR) spectra of VO2+-transferrin and (Fe3+)1(VO2+)1-transferrin. The EPR spectra of (Cr3+)1(VO2+)1-transferrin and of (Cr3+), (FE3+)1-transferrin indicate that that Cr3+ is bound to site B at pH 6.0. Transferrin was labeled at site A with 59Fe at pH 6.0 and at site B with 55Fe at pH 7.5. When the pH of the resulting preparation was lowered to 6.3 and the dissociated iron was separated by gel filtration, about ten times as much 55Fe as 59Fe was lost. The same EPR and isotopic-labeling experiments showed that Fe3+ added to transferrin at pH 7.5 binds to site A with about 90% selectivity.", "contents": "Different metal-binding properties of the two sites of human transferrin. Transferrin, the serum serum iron-transport protein which can bind two metal ions at physiologic pH, binds just one Fe3+, VO2+, or Cr3+ ion at pH 6.0. Fe3+ and VO2+ appear to be bound at the same site, designated A, based on electron paramagnetic resonance (EPR) spectra of VO2+-transferrin and (Fe3+)1(VO2+)1-transferrin. The EPR spectra of (Cr3+)1(VO2+)1-transferrin and of (Cr3+), (FE3+)1-transferrin indicate that that Cr3+ is bound to site B at pH 6.0. Transferrin was labeled at site A with 59Fe at pH 6.0 and at site B with 55Fe at pH 7.5. When the pH of the resulting preparation was lowered to 6.3 and the dissociated iron was separated by gel filtration, about ten times as much 55Fe as 59Fe was lost. The same EPR and isotopic-labeling experiments showed that Fe3+ added to transferrin at pH 7.5 binds to site A with about 90% selectivity."}
{"id": "PMID:189805", "title": "Evidence that the catalytic and regulatory functions of carbamylphosphate synthetase from Escherichia coli are not dependent on oligomer formation.", "content": "Carbamyl-phosphate synthetase from Escherichia coli is an allosteric enzyme which undergoes reversible association reactions in phosphate buffer. The positive allosteric effectors, ornithine, inosine 5'-monophosphate (IMP), and ammonia, facilitate oligomer formation, whereas uridine 5'-monophosphate (UMP), a negative effector, prevents or decreases oligomer formation. When the enzyme is immobilized by reaction with activated Sepharose, under conditions where the enzyme exists only as a monomer, nearly full catalytic activity is retained and the effects of ornithine, IMP, and UMP on the catalytic activity as a function of MgATP concentration are not significantly altered. Gel-filtration chromatography on Sephadex G-200 of catalytic quantities of the enzyme in the presence of all substrates showed that the elution volume was the same as that measured for the enzyme under conditions where it is known to exist in the monomer form. The specific activity of the enzyme does not increase when the concentration of the enzyme is increased 100-fold from a concentration at which the enzyme exists as monomer to a level at which the enzyme exists predominantly as oligomer. These results indicate that the monomer form of the enzyme is the principle active species and that oligomer formation is not directly related to enzyme activity or enzyme regulation.", "contents": "Evidence that the catalytic and regulatory functions of carbamylphosphate synthetase from Escherichia coli are not dependent on oligomer formation. Carbamyl-phosphate synthetase from Escherichia coli is an allosteric enzyme which undergoes reversible association reactions in phosphate buffer. The positive allosteric effectors, ornithine, inosine 5'-monophosphate (IMP), and ammonia, facilitate oligomer formation, whereas uridine 5'-monophosphate (UMP), a negative effector, prevents or decreases oligomer formation. When the enzyme is immobilized by reaction with activated Sepharose, under conditions where the enzyme exists only as a monomer, nearly full catalytic activity is retained and the effects of ornithine, IMP, and UMP on the catalytic activity as a function of MgATP concentration are not significantly altered. Gel-filtration chromatography on Sephadex G-200 of catalytic quantities of the enzyme in the presence of all substrates showed that the elution volume was the same as that measured for the enzyme under conditions where it is known to exist in the monomer form. The specific activity of the enzyme does not increase when the concentration of the enzyme is increased 100-fold from a concentration at which the enzyme exists as monomer to a level at which the enzyme exists predominantly as oligomer. These results indicate that the monomer form of the enzyme is the principle active species and that oligomer formation is not directly related to enzyme activity or enzyme regulation."}
{"id": "PMID:189806", "title": "Binding of allosteric effectors to carbamyl-phosphate synthetase from Escherichia coli.", "content": "The binding of ornithine and inosine 5'-monophosphate (IMP), positive allosteric effectors, and of uridine 5'-monophosphate (UMP), a negative allosteric effector, to carbamyl-phosphate synthetase from Escherichia coli was studied by the technique of equilibrium dialysis. The monomeric form of the enzyme has one binding site for each of the three allosteric ligands. The binding of UMP is inhibited by ornithine, IMP, MgATP, and ammonia (also a positive allosteric effector). Bicarbonate, L-glutamine, and adenosine 5'-triphosphate (ATP) (Mg2+ absent) had no effect on the binding of UMP. The affinity of the enzyme for UMP was increased if phosphate buffer was replaced by 2-amino-2-hydroxymethyl-1,3-propanediol (Tris) buffer. The binding of ornithine was inhibited by UMP and ammonia, enhanced by MgATP, MgADP, and IMP, and not affected by bicarbonate, L-glutamine, or ATP (Mg2+ absent). Ornithine and ammonia probably bind to the same site on the enzyme. The binding of IMP is facilitated by ornithine and ammonia, but is inhibited by MgATP or ATP, indicating that adenine nucleotides can also bind to the IMP binding site. The results of these binding studies are consistent with a scheme previously proposed in which the allosteric effectors function by stabilizing one or the other of two different conformational states of the enzyme which are in equilibrium with each other (Anderson, P.M., and Marvin, S.V. (1970), Biochemistry 9, 171). According to this scheme, binding of the substrate MgATP is greatly facilitated when the enzyme exists in the conformational state stabilized by the positive allosteric effectors.", "contents": "Binding of allosteric effectors to carbamyl-phosphate synthetase from Escherichia coli. The binding of ornithine and inosine 5'-monophosphate (IMP), positive allosteric effectors, and of uridine 5'-monophosphate (UMP), a negative allosteric effector, to carbamyl-phosphate synthetase from Escherichia coli was studied by the technique of equilibrium dialysis. The monomeric form of the enzyme has one binding site for each of the three allosteric ligands. The binding of UMP is inhibited by ornithine, IMP, MgATP, and ammonia (also a positive allosteric effector). Bicarbonate, L-glutamine, and adenosine 5'-triphosphate (ATP) (Mg2+ absent) had no effect on the binding of UMP. The affinity of the enzyme for UMP was increased if phosphate buffer was replaced by 2-amino-2-hydroxymethyl-1,3-propanediol (Tris) buffer. The binding of ornithine was inhibited by UMP and ammonia, enhanced by MgATP, MgADP, and IMP, and not affected by bicarbonate, L-glutamine, or ATP (Mg2+ absent). Ornithine and ammonia probably bind to the same site on the enzyme. The binding of IMP is facilitated by ornithine and ammonia, but is inhibited by MgATP or ATP, indicating that adenine nucleotides can also bind to the IMP binding site. The results of these binding studies are consistent with a scheme previously proposed in which the allosteric effectors function by stabilizing one or the other of two different conformational states of the enzyme which are in equilibrium with each other (Anderson, P.M., and Marvin, S.V. (1970), Biochemistry 9, 171). According to this scheme, binding of the substrate MgATP is greatly facilitated when the enzyme exists in the conformational state stabilized by the positive allosteric effectors."}
{"id": "PMID:189807", "title": "Effect of specific trifluoroacetylation of individual cytochrome c lysines on the reaction with cytochrome oxidase.", "content": "We have prepared three different cytochrome c derivatives, each containing a single specifically trifluoroacetylated lysine at residues 13, 55, and 99, respectively. The only modification that affected cytochrome c oxidase (EC 1.9.3.1) activity was that of lysine-13 at the top of the heme crevice. Trifluoroacetylation of lysine-13 increased the apparent Michaelis constant fivefold compared to that of native cytochrome c, but did not affect the maximum velocity. Trifluoroacetylation of lysine-55 at the left side of the cytochrome c molecule did not affect cytochrome oxidase activity in any way, nor did trifluoroacetylation of lysine-99 at the rear of the cytochrome c molecule. This indicates that the cytochrome oxidase binding site on cytochrome c involved only the front of the cytochrome c molecule and those lysines immediately surrounding the heme crevice.", "contents": "Effect of specific trifluoroacetylation of individual cytochrome c lysines on the reaction with cytochrome oxidase. We have prepared three different cytochrome c derivatives, each containing a single specifically trifluoroacetylated lysine at residues 13, 55, and 99, respectively. The only modification that affected cytochrome c oxidase (EC 1.9.3.1) activity was that of lysine-13 at the top of the heme crevice. Trifluoroacetylation of lysine-13 increased the apparent Michaelis constant fivefold compared to that of native cytochrome c, but did not affect the maximum velocity. Trifluoroacetylation of lysine-55 at the left side of the cytochrome c molecule did not affect cytochrome oxidase activity in any way, nor did trifluoroacetylation of lysine-99 at the rear of the cytochrome c molecule. This indicates that the cytochrome oxidase binding site on cytochrome c involved only the front of the cytochrome c molecule and those lysines immediately surrounding the heme crevice."}
{"id": "PMID:189808", "title": "Spin-label studies on the aqueous regions of phospholipid multilayers.", "content": "Water-soluble spin labels were used to study dimyristoyllecithin (DML) phospholipid multilayers. Previous studies report that there is a \"bound\" water region associated with dimyristoyllecithin containing about 10 molecules of water per phospholipid, a \"trapped\" water region located between the lamellae containing approximately 11 molecules per phospholipid, and a \"ftion show that certain water-soluble spin-label mol-cules have their motional properties differentially modified by these three water environements. Furthermore, the labels also reveal the onset of lipid-phase transitions even though they have high water solubility. A phosphate-containing spin label demonstrated strong an isotropic motion in the lipid-water system above the phase transition but not below. The addition of cholesterol to the DML-water system removed the anisotropic motion of 2,2,6,6-tetramehtyl-4-phosphopiperidine-N-oxyl (Tempophosphate) and obscured the detection bound, trapped, and free water. In addition to the change-charge interactions between Tempophosphate and DML, two other spin labels were used both in the charged and uncharged states. 2,2,6,6-Tetramethyl-4-aminopiperidine-N-oxyl (Tempamine) in the charged state showed extremely strong anisotropic motion, presumably due to the interaction between the charged amine and the phosphate group of DML. When only partially charged, Tempamine showed much less anisotropic motion. PCA was analyzed at pH values where the carboxyl group was protonated and unprotonated. The resulting interaction was different at the two pH values. These water-soluble spin labels mimic ionic or nonionic solutes. Upon freezing, the spin labels are shown to be expelled from the ice regions into the remaining aqueous regions. The usefulness of this approach in studying solute behavior when freezing occurs and potential studies involving aqueous regions of cytoplasm are considered.", "contents": "Spin-label studies on the aqueous regions of phospholipid multilayers. Water-soluble spin labels were used to study dimyristoyllecithin (DML) phospholipid multilayers. Previous studies report that there is a \"bound\" water region associated with dimyristoyllecithin containing about 10 molecules of water per phospholipid, a \"trapped\" water region located between the lamellae containing approximately 11 molecules per phospholipid, and a \"ftion show that certain water-soluble spin-label mol-cules have their motional properties differentially modified by these three water environements. Furthermore, the labels also reveal the onset of lipid-phase transitions even though they have high water solubility. A phosphate-containing spin label demonstrated strong an isotropic motion in the lipid-water system above the phase transition but not below. The addition of cholesterol to the DML-water system removed the anisotropic motion of 2,2,6,6-tetramehtyl-4-phosphopiperidine-N-oxyl (Tempophosphate) and obscured the detection bound, trapped, and free water. In addition to the change-charge interactions between Tempophosphate and DML, two other spin labels were used both in the charged and uncharged states. 2,2,6,6-Tetramethyl-4-aminopiperidine-N-oxyl (Tempamine) in the charged state showed extremely strong anisotropic motion, presumably due to the interaction between the charged amine and the phosphate group of DML. When only partially charged, Tempamine showed much less anisotropic motion. PCA was analyzed at pH values where the carboxyl group was protonated and unprotonated. The resulting interaction was different at the two pH values. These water-soluble spin labels mimic ionic or nonionic solutes. Upon freezing, the spin labels are shown to be expelled from the ice regions into the remaining aqueous regions. The usefulness of this approach in studying solute behavior when freezing occurs and potential studies involving aqueous regions of cytoplasm are considered."}
{"id": "PMID:189809", "title": "Actinomycin D complexes with oligonucleotides as models for the binding of the drug to DNA. Paramagnetic induced relaxation experiments on drug-nucleic acid complexes.", "content": "Mn(II) ions have been used as a paramagnetic probe to investigate the geometry of drug-oligonucleotide complexes. Nuclear magnetic resonance and electron spin resonance experiments show that Mn(II) ions bind approximately two orders of magnitude stronger to the 5'-terminal phosphate group than to the 3'-5' phosphodiester linkage of deoxydinucleotides. By using mixtures of nucleotides in which only one nucleotide contains a terminal phosphate group, the location of the Mn(II) ion in the drug-nucleotide-Mn(II) complexes may be preselected. The paramagnetic induced relaxation of the nuclear spin systems in these complexes has been used to investigate the geometry of these complexes. These data confirm that actinomycin D is able to recognize and preferentially bind guanine (as opposed to adenine) nucleotides in the quinoid portion of the phenoxazone ring, while both adenine and guanine will bind to the benzenoid portion of the phenoxazone ring. These results suggest that stacking forces are primarily responsible for the general requirement of a guanine base when actinomycin D binds to DNA.", "contents": "Actinomycin D complexes with oligonucleotides as models for the binding of the drug to DNA. Paramagnetic induced relaxation experiments on drug-nucleic acid complexes. Mn(II) ions have been used as a paramagnetic probe to investigate the geometry of drug-oligonucleotide complexes. Nuclear magnetic resonance and electron spin resonance experiments show that Mn(II) ions bind approximately two orders of magnitude stronger to the 5'-terminal phosphate group than to the 3'-5' phosphodiester linkage of deoxydinucleotides. By using mixtures of nucleotides in which only one nucleotide contains a terminal phosphate group, the location of the Mn(II) ion in the drug-nucleotide-Mn(II) complexes may be preselected. The paramagnetic induced relaxation of the nuclear spin systems in these complexes has been used to investigate the geometry of these complexes. These data confirm that actinomycin D is able to recognize and preferentially bind guanine (as opposed to adenine) nucleotides in the quinoid portion of the phenoxazone ring, while both adenine and guanine will bind to the benzenoid portion of the phenoxazone ring. These results suggest that stacking forces are primarily responsible for the general requirement of a guanine base when actinomycin D binds to DNA."}
{"id": "PMID:189810", "title": "bc1-Complex from beef heart. One-step purification by hydroxyapatite chromatography in Triton X-100, polypeptide pattern and respiratory chain characteristics.", "content": "A new simple method for the purification of the bc1-complex has been developed. The polypeptide composition of the complex was analysed by dodecyl sulfate-polyacrylamide gel electrophoresis. The content of chain components and phospholipids was determined. The b-type cytochromes were further characterized by their absorbance spectra and midpoint potentials. (1) Starting from a Triton X-100 extract of submitochondrial particles supplemented with antimycin, the bc1-complex is purified by adsorption chromatography on hydroxyapatite with citrate as specific eluant. (2) The complex splits in dodecyl sulfate into five main polypeptides with apparent molecular weight of 47, 44, 31, 11 and less than 10 kdalton. (3) The  purified complex has a heme-b content of 8.0 mumol/g protein and a cytochrome c1 content of 3.8 mumol/g protein. (4) The cytochromes show the typical absorbance spectra of cytochromes b-562 and b-565 and are present in approximately equal amounts with midpoint potentials of Em7 = + 100 mV and Em7 = + mV respectively. Carbon monoxide does not bind to the cytochromes. (5) The nonheme iron protein content of the complex is diminished to 0.6 mumol/g protein. (6) The use of the nonionic surfactant Triton X-100 leads to a complete loss of lipids and ubiquinone of the bc1-complex. (7) The complex contains no succinate dehydrogenase as indicated by the absence of the 69 kdalton subunit in the dodecyl sulfate gel electrophoresis. In addition, it lacks an ubiquinone cytochrome c reductase activity and other electron transferring activities. This may be inferred from an inhibition by antimycin and depletion of ubiquinone and phospholipids. The highly purified and relative stable complex can be prepared giving 50% yield and may be suitable for protein chemistry studies.", "contents": "bc1-Complex from beef heart. One-step purification by hydroxyapatite chromatography in Triton X-100, polypeptide pattern and respiratory chain characteristics. A new simple method for the purification of the bc1-complex has been developed. The polypeptide composition of the complex was analysed by dodecyl sulfate-polyacrylamide gel electrophoresis. The content of chain components and phospholipids was determined. The b-type cytochromes were further characterized by their absorbance spectra and midpoint potentials. (1) Starting from a Triton X-100 extract of submitochondrial particles supplemented with antimycin, the bc1-complex is purified by adsorption chromatography on hydroxyapatite with citrate as specific eluant. (2) The complex splits in dodecyl sulfate into five main polypeptides with apparent molecular weight of 47, 44, 31, 11 and less than 10 kdalton. (3) The  purified complex has a heme-b content of 8.0 mumol/g protein and a cytochrome c1 content of 3.8 mumol/g protein. (4) The cytochromes show the typical absorbance spectra of cytochromes b-562 and b-565 and are present in approximately equal amounts with midpoint potentials of Em7 = + 100 mV and Em7 = + mV respectively. Carbon monoxide does not bind to the cytochromes. (5) The nonheme iron protein content of the complex is diminished to 0.6 mumol/g protein. (6) The use of the nonionic surfactant Triton X-100 leads to a complete loss of lipids and ubiquinone of the bc1-complex. (7) The complex contains no succinate dehydrogenase as indicated by the absence of the 69 kdalton subunit in the dodecyl sulfate gel electrophoresis. In addition, it lacks an ubiquinone cytochrome c reductase activity and other electron transferring activities. This may be inferred from an inhibition by antimycin and depletion of ubiquinone and phospholipids. The highly purified and relative stable complex can be prepared giving 50% yield and may be suitable for protein chemistry studies."}
{"id": "PMID:189811", "title": "EPR signals of NADH: Q oxidoreductase. Shape and intensity.", "content": "(1) The EPR spectrum of Center 1 of NADH dehydrogenase in isolated Complex I or submitochondrial particles from beef heart consists of two overlapping nearly axial signals of the same intensity. They are defined as Center 1a (gll = 0.021, gl = 1.938) and Center 1b (gll = 2.021, gl = 1.928). (2) The line shape of the EPR spectrum of the Center 3+4 can be interpreted as an overlap of two rhombic signals of the same intensity. We define Center 3 by the g-values: gz=2.103, gy = 1.93-1.94, gx=1.884, and Center 4 by the values gz=2.04, gy=1.92-1.93, gx=1.863. (3) Direct quantitation of the individuals signals as well as computer stimulation suggests that the amount of the Centers 1a and 1b is only 25% of that of the other individuals centers and FMN. As EPR spectra of beef-heart submitochondrial particles at 10-20 K are nearly identical to those of Complex I, the same relative concentrations of the Fe-S centers are also present in the particles. (4) The signals either observed by us in EPR spectra of Complex I and submitochondrial particles at 4.2 K and high microwave powers can now be explained without assuming more than 5 paramagnetic centers in NADH dehydrogenase.", "contents": "EPR signals of NADH: Q oxidoreductase. Shape and intensity. (1) The EPR spectrum of Center 1 of NADH dehydrogenase in isolated Complex I or submitochondrial particles from beef heart consists of two overlapping nearly axial signals of the same intensity. They are defined as Center 1a (gll = 0.021, gl = 1.938) and Center 1b (gll = 2.021, gl = 1.928). (2) The line shape of the EPR spectrum of the Center 3+4 can be interpreted as an overlap of two rhombic signals of the same intensity. We define Center 3 by the g-values: gz=2.103, gy = 1.93-1.94, gx=1.884, and Center 4 by the values gz=2.04, gy=1.92-1.93, gx=1.863. (3) Direct quantitation of the individuals signals as well as computer stimulation suggests that the amount of the Centers 1a and 1b is only 25% of that of the other individuals centers and FMN. As EPR spectra of beef-heart submitochondrial particles at 10-20 K are nearly identical to those of Complex I, the same relative concentrations of the Fe-S centers are also present in the particles. (4) The signals either observed by us in EPR spectra of Complex I and submitochondrial particles at 4.2 K and high microwave powers can now be explained without assuming more than 5 paramagnetic centers in NADH dehydrogenase."}
{"id": "PMID:189812", "title": "Outer membrane of Salmonella typhimurium. Electron spin resonance studies.", "content": "The supramolecular structure of the outer membrane of Salmonella typhimurium that produces an Rc-type lipopolysaccharide was studied by adding spin-labeled fatty acid probes to membranes as well as model bilayers. Lipopolysaccharide of this organism apparently formed a bilayer structure in 0.2 M NaCl/0.01 M MgCl2, and the electron spin resonance spectra suggested that the motion of the segments of hydrocarbon chains near the carboxyl end was quite restricted even at high temperature; this is presumably due to the anchoring of more than a dozen fatty acid residues to a single backbone structure. In the presence of Mg2+, we could produce lipoplysaccharide-phospholipid mixed bilayers contining up to 50% (by weight) lipoplysaccharide. Their spectra showed no sign of major heterogeneity, and the maximum hyperfine splitting values were considerably larger than in phospholipid-only liposomes; these results suggest that the two components are finely interspersed and that the mobility of phospholipid hydrocarbons is severely restricted by the hydrocarbon chains of lipopolysaccharide. In spite of the presence of lipoplysaccharide in an amount equal to or exceeding that of phospholipids, the outer membrane produced spectra remarkably similar to those of the inner membrane, which does not contain lipoplysaccharide, and there was little sign of immobilization by lipopolysaccharides. Signals corresponding to the pure lipoplysaccharide phase were not detected, either. These results suggest that the phospholipids and lipopolysaccharides are segregated into separate domains in the outer membrane, and the fatty acid probes enter almost exclusively into the phospholipid domains. This conclusion was fully corroborated by determining, through the exchange broadening of line width, the total area of the domains that accommodated the spin label probes.", "contents": "Outer membrane of Salmonella typhimurium. Electron spin resonance studies. The supramolecular structure of the outer membrane of Salmonella typhimurium that produces an Rc-type lipopolysaccharide was studied by adding spin-labeled fatty acid probes to membranes as well as model bilayers. Lipopolysaccharide of this organism apparently formed a bilayer structure in 0.2 M NaCl/0.01 M MgCl2, and the electron spin resonance spectra suggested that the motion of the segments of hydrocarbon chains near the carboxyl end was quite restricted even at high temperature; this is presumably due to the anchoring of more than a dozen fatty acid residues to a single backbone structure. In the presence of Mg2+, we could produce lipoplysaccharide-phospholipid mixed bilayers contining up to 50% (by weight) lipoplysaccharide. Their spectra showed no sign of major heterogeneity, and the maximum hyperfine splitting values were considerably larger than in phospholipid-only liposomes; these results suggest that the two components are finely interspersed and that the mobility of phospholipid hydrocarbons is severely restricted by the hydrocarbon chains of lipopolysaccharide. In spite of the presence of lipoplysaccharide in an amount equal to or exceeding that of phospholipids, the outer membrane produced spectra remarkably similar to those of the inner membrane, which does not contain lipoplysaccharide, and there was little sign of immobilization by lipopolysaccharides. Signals corresponding to the pure lipoplysaccharide phase were not detected, either. These results suggest that the phospholipids and lipopolysaccharides are segregated into separate domains in the outer membrane, and the fatty acid probes enter almost exclusively into the phospholipid domains. This conclusion was fully corroborated by determining, through the exchange broadening of line width, the total area of the domains that accommodated the spin label probes."}
{"id": "PMID:189813", "title": "Prostaglandin receptor-adenylate cyclase system in plasma membranes of rat liver and ascites hepatomas, and the effect of GTP upon it.", "content": "1. Adenylate cyclase in plasma membranes from rat liver was stimulated  by prostaglandin E1, and to a lesser extent by prostaglandin E2. Prostaglandin F1alpha and A1 did not stimulate the cyclase. The prostaglandin E1-mediated activation was found to require GTP when the substrate ATP concentration was reduced from 3 mM to 0.3 mM in the  reaction mixture. Adenylate cyclase of the plasma membranes from rat ascites hepatomas AH-130 and AH-7974 was not stimulated by prostaglandin E1 in the presence or the absence of GTP, although the basal activity of adenylate cyclase as well as its stimulation by GTP alone were similar to normal liver plasma membranes. 2. Liver plasma membranes were found to have two specific binders for [3H] prostaglandin E1 with dissociation constants of 17.6-10(-9) M and 13.6-10(8) M (37 degrees C) and one specific binder for [3H]prostaglandin F2alpha with a dissociation constant of 2.31-10(8) M (37 degrees C). The specific binders for prostaglandin E1 could not be detected in the hepatoma plasma membranes. 3. Binding of [3H] prostaglandin E1 to the liver plasma membranes was exchange by, GTP dGPT, GDP, ATP and GMP-P(N)P, but not by GMP, CGMP, DTTP, UTP or CTP. The increase in the binding of [3H] prostaglandin E1 was found to be due to the increased affinity of the specific binders to prostaglandin F2alpha was not affected by GTP. 4. GTP alone was found to increase V of adenylate cyclase of liver plasma membranes, while GTP plus prostaglandin E1 was found to decrease Km of adenylate cyclase in addition to the increase of V to a further extent.", "contents": "Prostaglandin receptor-adenylate cyclase system in plasma membranes of rat liver and ascites hepatomas, and the effect of GTP upon it. 1. Adenylate cyclase in plasma membranes from rat liver was stimulated  by prostaglandin E1, and to a lesser extent by prostaglandin E2. Prostaglandin F1alpha and A1 did not stimulate the cyclase. The prostaglandin E1-mediated activation was found to require GTP when the substrate ATP concentration was reduced from 3 mM to 0.3 mM in the  reaction mixture. Adenylate cyclase of the plasma membranes from rat ascites hepatomas AH-130 and AH-7974 was not stimulated by prostaglandin E1 in the presence or the absence of GTP, although the basal activity of adenylate cyclase as well as its stimulation by GTP alone were similar to normal liver plasma membranes. 2. Liver plasma membranes were found to have two specific binders for [3H] prostaglandin E1 with dissociation constants of 17.6-10(-9) M and 13.6-10(8) M (37 degrees C) and one specific binder for [3H]prostaglandin F2alpha with a dissociation constant of 2.31-10(8) M (37 degrees C). The specific binders for prostaglandin E1 could not be detected in the hepatoma plasma membranes. 3. Binding of [3H] prostaglandin E1 to the liver plasma membranes was exchange by, GTP dGPT, GDP, ATP and GMP-P(N)P, but not by GMP, CGMP, DTTP, UTP or CTP. The increase in the binding of [3H] prostaglandin E1 was found to be due to the increased affinity of the specific binders to prostaglandin F2alpha was not affected by GTP. 4. GTP alone was found to increase V of adenylate cyclase of liver plasma membranes, while GTP plus prostaglandin E1 was found to decrease Km of adenylate cyclase in addition to the increase of V to a further extent."}
{"id": "PMID:189814", "title": "Magnetic resonance study of the distribution of 2,2,6,6-tetramethylpiperidine-N-oxyl in phosphatidylcholine bilayers.", "content": "With the aid of paramagentic praseodymium ions the resonances at 60 MHz of the inward and outward facing choline methyl protons of sonicated egg yolk phosphatidylcholine vesicles were resolved. The subsequent addition of 2,2,6,6,-tetramethylpiperidine-N-oxyl (TEMPO) to the vesicle suspension broadened the inner and outer resonances equally. TEMPO easily penetrates the egg yolk phosphatidylcholine vesicles and has free access to the entire lipid volume above the gel to liquid crystalline transition temperature. The electron spin resonance (ESR) spectrum of TEMPO in the egg yolk phosphatidylcholine suspension exhibits features indicating that TEMPO dissolves principally in the hydrocarbon portion of the egg yolk phosphatidylcholine bilayer. The egg yolk phosphatidylcholine methylene chain proton resonances are also broadened by TEMPO notably to a greater extent than the choline methyl resonances. These data indicate that TEMPO should be more sensitive to the melting behavior of the fatty acyl chains of phospholipid suspensions than to the polar head groups.", "contents": "Magnetic resonance study of the distribution of 2,2,6,6-tetramethylpiperidine-N-oxyl in phosphatidylcholine bilayers. With the aid of paramagentic praseodymium ions the resonances at 60 MHz of the inward and outward facing choline methyl protons of sonicated egg yolk phosphatidylcholine vesicles were resolved. The subsequent addition of 2,2,6,6,-tetramethylpiperidine-N-oxyl (TEMPO) to the vesicle suspension broadened the inner and outer resonances equally. TEMPO easily penetrates the egg yolk phosphatidylcholine vesicles and has free access to the entire lipid volume above the gel to liquid crystalline transition temperature. The electron spin resonance (ESR) spectrum of TEMPO in the egg yolk phosphatidylcholine suspension exhibits features indicating that TEMPO dissolves principally in the hydrocarbon portion of the egg yolk phosphatidylcholine bilayer. The egg yolk phosphatidylcholine methylene chain proton resonances are also broadened by TEMPO notably to a greater extent than the choline methyl resonances. These data indicate that TEMPO should be more sensitive to the melting behavior of the fatty acyl chains of phospholipid suspensions than to the polar head groups."}
{"id": "PMID:189815", "title": "Cooperativity of the phase transition in single- and multibilayer lipid vesicles.", "content": "The effect of membrane morphology on the cooperativity of the ordered-fluid, lipid phase transition has been investigated by comparing the transition widths in extended, multibilayer dispersons of dimyristoyl phosphatidyl-choline, and also of dipalmitoyl phosphatidylcholine, with those in the small, single-bilayer vesicles obtained by sonication. The electron spin resonance spectra of three different spin-labelled probes, 2,2,6,6-tetramethylpiperdine-N-oxyl, phosphatidylcholine and stearic acid, and also 90 degrees light scattering and optical turbidity measurements were used as indicators of the phase transition. In all cases the transition was broader in the single-bilayer vesicles than in the multibilayer dispersions, corresponding to a decreased cooperativity on going to the small vesicles. Comparison of the light scattering properties of centrifuged and uncentrifuged, sonicated vesicles suggests that these are particularly sensitive to the presence of intermediate-size particles, and thus the spin label measurements are likely to give a more reliable measure of the degree of cooperativity of the small, single-bilayer vesicles. Application of the Zimm and Bragg theory ((1959) J. Chem. Phys. 31, 526-535) of cooperative transitions to the two-dimensional bilayer system shows that the size of the cooperative unit, 1/square root sigma, is a measure of the mean number of molecules per perimeter molecule, in a given region of ordered or fluid lipid at the centre of the transition. From this result it is found that it is the vesicle size which limits the cooperativity of the transition in the small, single-bilayer vesicles. The implications for the effect of membrane structure and morphology on the cooperativity of phase transitions in biological membranes, and for the possibility of achieving lateral communication in the plane of the membrane, are discussed.", "contents": "Cooperativity of the phase transition in single- and multibilayer lipid vesicles. The effect of membrane morphology on the cooperativity of the ordered-fluid, lipid phase transition has been investigated by comparing the transition widths in extended, multibilayer dispersons of dimyristoyl phosphatidyl-choline, and also of dipalmitoyl phosphatidylcholine, with those in the small, single-bilayer vesicles obtained by sonication. The electron spin resonance spectra of three different spin-labelled probes, 2,2,6,6-tetramethylpiperdine-N-oxyl, phosphatidylcholine and stearic acid, and also 90 degrees light scattering and optical turbidity measurements were used as indicators of the phase transition. In all cases the transition was broader in the single-bilayer vesicles than in the multibilayer dispersions, corresponding to a decreased cooperativity on going to the small vesicles. Comparison of the light scattering properties of centrifuged and uncentrifuged, sonicated vesicles suggests that these are particularly sensitive to the presence of intermediate-size particles, and thus the spin label measurements are likely to give a more reliable measure of the degree of cooperativity of the small, single-bilayer vesicles. Application of the Zimm and Bragg theory ((1959) J. Chem. Phys. 31, 526-535) of cooperative transitions to the two-dimensional bilayer system shows that the size of the cooperative unit, 1/square root sigma, is a measure of the mean number of molecules per perimeter molecule, in a given region of ordered or fluid lipid at the centre of the transition. From this result it is found that it is the vesicle size which limits the cooperativity of the transition in the small, single-bilayer vesicles. The implications for the effect of membrane structure and morphology on the cooperativity of phase transitions in biological membranes, and for the possibility of achieving lateral communication in the plane of the membrane, are discussed."}
{"id": "PMID:189816", "title": "Studies on bovine adrenal estrogen sulfotransferase. III. Facile synthesis of 3'-phospho- and 2'-phosphoadenosine 5'-phosphosulfate.", "content": "A practical synthesis of 3'-phosphoadenosine 5'-phosphosulfate (IV) in yields of 68-72% from adenosine 2',3'-cyclic phosphate 5'-phosphate (II) is described. Reaction of II with triethylamine-N-sulfonic acid affords adenosine 2',3'-cyclic phosphate 5'-phosphosulfate (III) which, on treatment with ribonuclease-T2, provides IV. Spleen phosphodiesterase, on the other hand, converts III to 2'-phosphoadenosine 5'-phosphosulfate (V). The biological activity of IV, measured by sulfate transfer to [6,7-3H2]estrone as mediated by bovine adrenal estrone sulfotransferase (3'-phosphoadenylyl-sulfate:estrone 3-sulfotransferase, EC 2.8.2.4), is identical with that obtained with a sample of IV prepared by an established biochemical procedure. By contrast, V exhibits approximately one-third the activity of the natural isomer.", "contents": "Studies on bovine adrenal estrogen sulfotransferase. III. Facile synthesis of 3'-phospho- and 2'-phosphoadenosine 5'-phosphosulfate. A practical synthesis of 3'-phosphoadenosine 5'-phosphosulfate (IV) in yields of 68-72% from adenosine 2',3'-cyclic phosphate 5'-phosphate (II) is described. Reaction of II with triethylamine-N-sulfonic acid affords adenosine 2',3'-cyclic phosphate 5'-phosphosulfate (III) which, on treatment with ribonuclease-T2, provides IV. Spleen phosphodiesterase, on the other hand, converts III to 2'-phosphoadenosine 5'-phosphosulfate (V). The biological activity of IV, measured by sulfate transfer to [6,7-3H2]estrone as mediated by bovine adrenal estrone sulfotransferase (3'-phosphoadenylyl-sulfate:estrone 3-sulfotransferase, EC 2.8.2.4), is identical with that obtained with a sample of IV prepared by an established biochemical procedure. By contrast, V exhibits approximately one-third the activity of the natural isomer."}
{"id": "PMID:189817", "title": "Cyclic nucleotide phosphodiesterases in the cricket, Acheta domesticus.", "content": "Exceptionally high levels of guanosine 3'-5'-cyclic monophosphate (cyclic GMP) in the accessory reproductive gland of the male house cricket, Acheta domesticus, led to an investigation of cyclic nucleotide phosphodiesterase (EC 3.1.4.--) as a possible regulatory enzyme. Cricket cyclic nucleotide phosphodiesterase activity with cyclic GMP or cyclic AMP as substrate had a pH optimum around 9.0, required Mg2+ or Mn2+ for maximal activity, and was inhibited by EDTA and methylxanthines. Cyclic GMP phosphodiesterase occurred mainly in the soluble fraction of homogenates of accessory glands or whole crickets, but cyclic AMP phosphodiesterase in the accessory gland was primarily particulate. Kinetic analysis indicated three forms of cyclic GMP phosphodiesterase, with Km values at 2.9 muM, 71 muM and 1.5 mM. Chromatography of whole cricket or accessory gland extracts on DEAE cellulose gave an initial peak having comparable activity with either cyclic GMP or cyclic AMP, and a second peak specific for cyclic AMP. There were no appreciable changes in the specific activity or kinetic properties of accessory gland cyclic GMP phosphodiesterase during a developmental period over which cyclic GMP levels rise more than 500-fold. Thus, the accumulation of cyclic GMP in the accessory gland is probably not associated with concomitant developmental modulation of phosphodiesterase activity.", "contents": "Cyclic nucleotide phosphodiesterases in the cricket, Acheta domesticus. Exceptionally high levels of guanosine 3'-5'-cyclic monophosphate (cyclic GMP) in the accessory reproductive gland of the male house cricket, Acheta domesticus, led to an investigation of cyclic nucleotide phosphodiesterase (EC 3.1.4.--) as a possible regulatory enzyme. Cricket cyclic nucleotide phosphodiesterase activity with cyclic GMP or cyclic AMP as substrate had a pH optimum around 9.0, required Mg2+ or Mn2+ for maximal activity, and was inhibited by EDTA and methylxanthines. Cyclic GMP phosphodiesterase occurred mainly in the soluble fraction of homogenates of accessory glands or whole crickets, but cyclic AMP phosphodiesterase in the accessory gland was primarily particulate. Kinetic analysis indicated three forms of cyclic GMP phosphodiesterase, with Km values at 2.9 muM, 71 muM and 1.5 mM. Chromatography of whole cricket or accessory gland extracts on DEAE cellulose gave an initial peak having comparable activity with either cyclic GMP or cyclic AMP, and a second peak specific for cyclic AMP. There were no appreciable changes in the specific activity or kinetic properties of accessory gland cyclic GMP phosphodiesterase during a developmental period over which cyclic GMP levels rise more than 500-fold. Thus, the accumulation of cyclic GMP in the accessory gland is probably not associated with concomitant developmental modulation of phosphodiesterase activity."}
{"id": "PMID:189818", "title": "EPR determination of the Co(II)-free radical magnetic geometry of the \"doublet\" species arising in a coenzyme B-12-enzyme reaction.", "content": "The physical significance of the observed structure of the EPR signal, commonly known as the \"doublet\" spectrum, is that it contains information not only about the exchange coupling but also about the geometry of the magnetic dipole-dipole spin-spin coupling. We can show this because we have developed a general method of analysis applicable to this type of system and because we demand a quantitative fit of theory to experiment at two microwave frequencies. We have chosen the \"doublet\" free radical signal, which arises in the ribonucleotide reductase-5'-deoxyadenosylcobalamin system (from Lactobacillus leichmannii, see Hamilton et al., Biochemistry 11, 4696--4705 (1972)), for study, for the particular reason that the 35 GHz \"doublet\" spectrum has three components (in this case) rather than two, which provides an important test of the recently proposed model of isotropic exchange coupling by Schepler et al. ((1975) Biochim. Biophys. Acta 397, 510--518). We find that a quantitative fit to the EPR \"doublet\" lineshape can be obtained with a model of isotropic exchange, and a \"point\" magnetic dipole-dipole interaction acting over a distance of 9.9 A with the radical located approx. 34 degrees off the principal gzz axis and less than 1 degree off the principal gxx axis of the Co(II) in the corrin ring. Quantitative fits of the doublet portion of the observed lineshape at both 9 and 35 GHz were achieved with this model, assuming an axially symmetric free radical signal and a Gaussian spin-packet lineshape with isotropic linewidth.", "contents": "EPR determination of the Co(II)-free radical magnetic geometry of the \"doublet\" species arising in a coenzyme B-12-enzyme reaction. The physical significance of the observed structure of the EPR signal, commonly known as the \"doublet\" spectrum, is that it contains information not only about the exchange coupling but also about the geometry of the magnetic dipole-dipole spin-spin coupling. We can show this because we have developed a general method of analysis applicable to this type of system and because we demand a quantitative fit of theory to experiment at two microwave frequencies. We have chosen the \"doublet\" free radical signal, which arises in the ribonucleotide reductase-5'-deoxyadenosylcobalamin system (from Lactobacillus leichmannii, see Hamilton et al., Biochemistry 11, 4696--4705 (1972)), for study, for the particular reason that the 35 GHz \"doublet\" spectrum has three components (in this case) rather than two, which provides an important test of the recently proposed model of isotropic exchange coupling by Schepler et al. ((1975) Biochim. Biophys. Acta 397, 510--518). We find that a quantitative fit to the EPR \"doublet\" lineshape can be obtained with a model of isotropic exchange, and a \"point\" magnetic dipole-dipole interaction acting over a distance of 9.9 A with the radical located approx. 34 degrees off the principal gzz axis and less than 1 degree off the principal gxx axis of the Co(II) in the corrin ring. Quantitative fits of the doublet portion of the observed lineshape at both 9 and 35 GHz were achieved with this model, assuming an axially symmetric free radical signal and a Gaussian spin-packet lineshape with isotropic linewidth."}
{"id": "PMID:189819", "title": "Chloroquine-induced interference with degradation of serum lipoproteins in rat liver, studied in vivo and in vitro.", "content": "The effect of chloroquine, an inhibitor of certain lysosomal enzymes including cathepsin B (EC 3.4.22.1), on the degradation of serum lipoproteins in rat liver was studied in vivo and in liver homogenates. Chloroquine had no effect on the clearance from the circulation of 125I-labeled rat or human very low density lipoproteins or human low density lipoproteins. Pretreatment with chloroquine for 3 h, resulted in a 2-2.5 fold increase in 125i-labeled very low density lipoprotein recovered in the liver 45 min after injection of the homologous and heterologous lipoproteins. This effect was evident on both the 125I-labeled protein and 125I-labeled lipid moiety. 30 min after the injection of [3H]-cholesterol linoleate-labeled very low density lipoproteins, 70% of the injected label was recovered in the liver, both in control and chloroquine-treated rats. Since the perl and 20% in the experimental group, it was concluded that chloroquine interferes with the hydrolysis of [3H]cholesterol linoleate. Following injection of 125I-labeled human low density lipoproteins only 4% of the injected lipoprotein was recovered in the liver of control rats and not more than 10% after chloroquine treatment, when about 50% had been cleared from the circulation. Hence, while very low density lipoprotein protein and cholesterol ester are catabolized in the liver, the catabolism of low density lipoproteins occurs mainly in extra-hepatic tissues. Using post-nuclear liver suprnatant, optimal degradation of various serum lipoproteins was found at pH 4.4, and chloroquine inhibited their degradation. Degradation of very low density and low density lipoproteins was completely inhibited at 0.05 M chloroquine, while less pronounced inhibition was seen with high density lipoproteins, apolipoproteins and apolipoprotein AI. These results indicate that liver acid hydrolases in vivo participate in the degradation of serum lipoproteins. Cathepsin B is apparently responsible for the degradation of aplipoprotein B, while other cathepsins might also be active in the degradation of this and the other apolipoproteins.", "contents": "Chloroquine-induced interference with degradation of serum lipoproteins in rat liver, studied in vivo and in vitro. The effect of chloroquine, an inhibitor of certain lysosomal enzymes including cathepsin B (EC 3.4.22.1), on the degradation of serum lipoproteins in rat liver was studied in vivo and in liver homogenates. Chloroquine had no effect on the clearance from the circulation of 125I-labeled rat or human very low density lipoproteins or human low density lipoproteins. Pretreatment with chloroquine for 3 h, resulted in a 2-2.5 fold increase in 125i-labeled very low density lipoprotein recovered in the liver 45 min after injection of the homologous and heterologous lipoproteins. This effect was evident on both the 125I-labeled protein and 125I-labeled lipid moiety. 30 min after the injection of [3H]-cholesterol linoleate-labeled very low density lipoproteins, 70% of the injected label was recovered in the liver, both in control and chloroquine-treated rats. Since the perl and 20% in the experimental group, it was concluded that chloroquine interferes with the hydrolysis of [3H]cholesterol linoleate. Following injection of 125I-labeled human low density lipoproteins only 4% of the injected lipoprotein was recovered in the liver of control rats and not more than 10% after chloroquine treatment, when about 50% had been cleared from the circulation. Hence, while very low density lipoprotein protein and cholesterol ester are catabolized in the liver, the catabolism of low density lipoproteins occurs mainly in extra-hepatic tissues. Using post-nuclear liver suprnatant, optimal degradation of various serum lipoproteins was found at pH 4.4, and chloroquine inhibited their degradation. Degradation of very low density and low density lipoproteins was completely inhibited at 0.05 M chloroquine, while less pronounced inhibition was seen with high density lipoproteins, apolipoproteins and apolipoprotein AI. These results indicate that liver acid hydrolases in vivo participate in the degradation of serum lipoproteins. Cathepsin B is apparently responsible for the degradation of aplipoprotein B, while other cathepsins might also be active in the degradation of this and the other apolipoproteins."}
{"id": "PMID:189820", "title": "Partial purification and characterization of NAD-dependent 7alpha-hydroxysteroid dehydrogenase from Bacteroides thetaiotaomicron.", "content": "A NAD-dependent 7alpha-hydroxysteroid dehydrogenase was purified 18-fold over the activity in crude cell extracts prepared from Bacteroides thetaiotaomicron NCTC 10852 using Bio-Gel A 1.5-M column chromatography. A molecular weight of 320 000 was estimated for the partially purified intact enzyme. Substrate saturation kinetics were performed using the 18-fold purified enzyme and the lowest Km values were obtained for 3alpha,7alpha-dihydroxy bile acid and bile salt substrates including chenodeoxycholic acid (Km 0.048 mM), glycochenodeoxycholic acid (Km 0.083 mM) and taurochenodeoxycholic acid (Km 0.059 mM). In contrast, 3alpha,7alpha,12alpha-trihydroxy bile acid and bile salts had higher Km values, i.e. cholic acid (Km 0.22 mM), glycoholic acid Km 0.32 mM) and taurocholic acid Km 0.26 mM). NAD had a Km value of 0.20 mM. The possible physiological significance of 7alpha-hydroxy bile acid oxidation to intestinal bacteroides strains was accessed by determining the rate of conversion of [14C]-cholic acid to 7-ketodeoxy[14C]cholic acid by whole cell suspensions under different incubation conditions. The rate of biotransformation of bile acid to keto-bile acid incubated anaerobically under N2 gas increased markedly when potential electron acceptors such as fumarate (10 mM) or menadione (4 mM) was added exogenously. These results suggest that bile acid oxidation reactions may be linked to energy-generating systems in this bacterium.", "contents": "Partial purification and characterization of NAD-dependent 7alpha-hydroxysteroid dehydrogenase from Bacteroides thetaiotaomicron. A NAD-dependent 7alpha-hydroxysteroid dehydrogenase was purified 18-fold over the activity in crude cell extracts prepared from Bacteroides thetaiotaomicron NCTC 10852 using Bio-Gel A 1.5-M column chromatography. A molecular weight of 320 000 was estimated for the partially purified intact enzyme. Substrate saturation kinetics were performed using the 18-fold purified enzyme and the lowest Km values were obtained for 3alpha,7alpha-dihydroxy bile acid and bile salt substrates including chenodeoxycholic acid (Km 0.048 mM), glycochenodeoxycholic acid (Km 0.083 mM) and taurochenodeoxycholic acid (Km 0.059 mM). In contrast, 3alpha,7alpha,12alpha-trihydroxy bile acid and bile salts had higher Km values, i.e. cholic acid (Km 0.22 mM), glycoholic acid Km 0.32 mM) and taurocholic acid Km 0.26 mM). NAD had a Km value of 0.20 mM. The possible physiological significance of 7alpha-hydroxy bile acid oxidation to intestinal bacteroides strains was accessed by determining the rate of conversion of [14C]-cholic acid to 7-ketodeoxy[14C]cholic acid by whole cell suspensions under different incubation conditions. The rate of biotransformation of bile acid to keto-bile acid incubated anaerobically under N2 gas increased markedly when potential electron acceptors such as fumarate (10 mM) or menadione (4 mM) was added exogenously. These results suggest that bile acid oxidation reactions may be linked to energy-generating systems in this bacterium."}
{"id": "PMID:189821", "title": "Regulation of lipolysis and cyclic AMP synthesis through energy supply in isolated human fat cells.", "content": "The effects of glucose and of various inhibitors of glycolysis or of oxidative phosphorylation on stimulated lipolysis and on intracellular cyclic AMP and ATP levels were investigated in isolated human fat cells. The glycolysis inhibitors, NaF and monoiodoacetate, inhibited epinephrine or theophylline-stimulated lipolysis and parallely reduced the intracellular cyclic AMP and ATP levels; however, neither NaF nor monoidoacetate significantly affected dibutyryl cyclic AMP-induced lipolysis. Removal of glucose from the medium also reduced the rate of epinephrine-stimulated lipolysis and the intracellular cyclic AMP and ATP levels but failed to modify the lipolytic activity of dibutyryl cyclic AMP. The oxidative phosphorylation inhibitors, antimycin A and, under fixed conditions, 2,4-dinitrophenol also strongly decreased the adipocyte cyclic AMP and ATP levels but inhibited as well the rate of epinephrine- and of dibutyryl cyclic AMP-induced lipolysis. N-Ethylmaleimide, a mixed glycolysis and oxidative phosphorylation inhibitor, not only reduced the intracellular cyclic AMP and ATP levels and epinephrine- or theophylline-induced lipolysis, but also that stimulated by dibutyryl cyclic AMP. When glycolysis was almost fully inhibited, human fat cells were insensitive to epinephrine but remained fully responsive to dibutyryl cyclic AMP. These results, showing a relationship between ATP availability, cyclic AMP synthesis and lipolysis, suggest a different ATP requirement for cyclic AMP synthesis and triacylglycerol lipase activation, a difference which could explain why ATP issued from glucose breakdown appears to be a determinant factor for cyclic AMP synthesis, but not for triacylglycerol lipase activation in human fat cells.", "contents": "Regulation of lipolysis and cyclic AMP synthesis through energy supply in isolated human fat cells. The effects of glucose and of various inhibitors of glycolysis or of oxidative phosphorylation on stimulated lipolysis and on intracellular cyclic AMP and ATP levels were investigated in isolated human fat cells. The glycolysis inhibitors, NaF and monoiodoacetate, inhibited epinephrine or theophylline-stimulated lipolysis and parallely reduced the intracellular cyclic AMP and ATP levels; however, neither NaF nor monoidoacetate significantly affected dibutyryl cyclic AMP-induced lipolysis. Removal of glucose from the medium also reduced the rate of epinephrine-stimulated lipolysis and the intracellular cyclic AMP and ATP levels but failed to modify the lipolytic activity of dibutyryl cyclic AMP. The oxidative phosphorylation inhibitors, antimycin A and, under fixed conditions, 2,4-dinitrophenol also strongly decreased the adipocyte cyclic AMP and ATP levels but inhibited as well the rate of epinephrine- and of dibutyryl cyclic AMP-induced lipolysis. N-Ethylmaleimide, a mixed glycolysis and oxidative phosphorylation inhibitor, not only reduced the intracellular cyclic AMP and ATP levels and epinephrine- or theophylline-induced lipolysis, but also that stimulated by dibutyryl cyclic AMP. When glycolysis was almost fully inhibited, human fat cells were insensitive to epinephrine but remained fully responsive to dibutyryl cyclic AMP. These results, showing a relationship between ATP availability, cyclic AMP synthesis and lipolysis, suggest a different ATP requirement for cyclic AMP synthesis and triacylglycerol lipase activation, a difference which could explain why ATP issued from glucose breakdown appears to be a determinant factor for cyclic AMP synthesis, but not for triacylglycerol lipase activation in human fat cells."}
{"id": "PMID:189822", "title": "Radioimmunoassay of arginine-rich apolipoprotein of rat serum.", "content": "A double-antibody radioimmunoassay was developed for quantification of rat arginine-rich apolipoprotein in sodium decyl sulfate. Arginine-rich protein, labeled with 125I by the chloramine-T method, had the same chromatographic characteristics on Sephadex G-200 as unlabeled arginine-rich protein and up to 70% of 125I-labeled arginine-rich protein was precipitated by antisera to arginine-rich protein in rabbits. The assay is sensitive at the level of 1-10 ng and has intraassay and interassay coefficients of variation of 5.4 and 6.8%, respectively. The specificity of the assay was established by competitive displacement of 125I-labeled arginine-rich protein from its antiserum by arginine-rich protein and lipoproteins containing this protein, but not by rat albumin or other purified apolipoproteins. Immunoreactivity of rat serum and lipoproteins was complete as demonstrated by comparison with their delipidated form. The accuracy of the immunoassay was further substantiated by comparison with the amount of arginine-rich protein in chromatographic fractions of total apoprotein of very low and high density lipoproteins, and by recovery experiments in ultracentrifugally separated fractions of serum. In contrast to an immunoassay reported previously for rat apo A-I, sodium decyl sulfate was not required for complete immunoreactivity of serum and lipoproteins. The inclusion of sodium decyl sulfate (9 mM final concentration) was necessary, however, for stability of labeled and unlabeled preparations of arginine-rich protein. Content (weight %, means values +/- S.D.), of immunoassayable arginine-rich protein in isolated lipoproteins was 15 +/- 1.5% in very density lipoproteins; 6.8% in low density lipoproteins (1.02 less than d less than 1.04 g/m); 7.1 +/- 0.3% in high density lipoproteins; and 4.8 +/- 0.5% in lymph chylomicrons. Concentration in whole serum was 18.1 +/- 1.4 and 20.4 +/- 2.3 mg/dl for male and female rats, respectively. Only about 55% of arginine-rich protein was recovered in the major lipoprotein classes and about 40% was in \"lipoprotein-free\" serum (d greater than 1.25 g/ml). Among the lipoproteins, the high density lipoprotein fraction contained twice the amount of arginine-rich protein recovered in very low or low density lipoproteins (26.6 vs. 13.5 and 13.4%, respectively). The significance of the large amount of arginine-rich protein in the 1.25 g/ml infranatant fraction is not apparent. Although repetitive centrifugation did not alter the amount recovered in this fraction, the possibility of an artifact induced by centrifugation and high salt concentration cannot be excluded.", "contents": "Radioimmunoassay of arginine-rich apolipoprotein of rat serum. A double-antibody radioimmunoassay was developed for quantification of rat arginine-rich apolipoprotein in sodium decyl sulfate. Arginine-rich protein, labeled with 125I by the chloramine-T method, had the same chromatographic characteristics on Sephadex G-200 as unlabeled arginine-rich protein and up to 70% of 125I-labeled arginine-rich protein was precipitated by antisera to arginine-rich protein in rabbits. The assay is sensitive at the level of 1-10 ng and has intraassay and interassay coefficients of variation of 5.4 and 6.8%, respectively. The specificity of the assay was established by competitive displacement of 125I-labeled arginine-rich protein from its antiserum by arginine-rich protein and lipoproteins containing this protein, but not by rat albumin or other purified apolipoproteins. Immunoreactivity of rat serum and lipoproteins was complete as demonstrated by comparison with their delipidated form. The accuracy of the immunoassay was further substantiated by comparison with the amount of arginine-rich protein in chromatographic fractions of total apoprotein of very low and high density lipoproteins, and by recovery experiments in ultracentrifugally separated fractions of serum. In contrast to an immunoassay reported previously for rat apo A-I, sodium decyl sulfate was not required for complete immunoreactivity of serum and lipoproteins. The inclusion of sodium decyl sulfate (9 mM final concentration) was necessary, however, for stability of labeled and unlabeled preparations of arginine-rich protein. Content (weight %, means values +/- S.D.), of immunoassayable arginine-rich protein in isolated lipoproteins was 15 +/- 1.5% in very density lipoproteins; 6.8% in low density lipoproteins (1.02 less than d less than 1.04 g/m); 7.1 +/- 0.3% in high density lipoproteins; and 4.8 +/- 0.5% in lymph chylomicrons. Concentration in whole serum was 18.1 +/- 1.4 and 20.4 +/- 2.3 mg/dl for male and female rats, respectively. Only about 55% of arginine-rich protein was recovered in the major lipoprotein classes and about 40% was in \"lipoprotein-free\" serum (d greater than 1.25 g/ml). Among the lipoproteins, the high density lipoprotein fraction contained twice the amount of arginine-rich protein recovered in very low or low density lipoproteins (26.6 vs. 13.5 and 13.4%, respectively). The significance of the large amount of arginine-rich protein in the 1.25 g/ml infranatant fraction is not apparent. Although repetitive centrifugation did not alter the amount recovered in this fraction, the possibility of an artifact induced by centrifugation and high salt concentration cannot be excluded."}
{"id": "PMID:189823", "title": "Solvent denaturation of globular proteins: unfolding by the monoalkyl- and dialkyl-substituted formamides and ureas.", "content": "The effects of the monoalkyl and dialkyl-substituted formamide series of denaturants on the native conformation of sperm whale myoglobin, horse heart cytochrome c, and Glycera dibranciata (single chain) hemoglobin have been investigated by spectral measurements in the Soret region (409 and 422 nm) and optical rotation measurements (265nm). The effectiveness of these two classes of protein denaturants is similar to the other straight-chain compounds of the urea, amide, and alcohol classes, examined in previous investigations from our laboratory. Their denaturing effectiveness is found to increase with increasing chain length or hydrocarbon content of the substituent alkyl groups. Application of the Peller and Flory equation to the denaturation data of the formamides shows that both the polar and the nonpolar group contributions to the protein-denaturant interactions have to be taken into account in order to correctly predict the observed denaturation midpoints. Additivity of the hydrophobic, KH\u00f8, and the polar, Kp, group contributions to the binding constants, KB = nKH\u00f8 + Kp, with n = 1 or 2 for the mono- of the di-alkyl substituted denaturants gave best account of the experimental data. The KH\u00f8 values used were based on free energy transfer data of various alkyl groups or the Scheraga-Nemethy theory of hydrophobic bonding. The assumption of group contributions of the denaturant to KB were also applied to the denaturation data of the unsubstituted amides and some examples of the monoalkyl and symmetrically substituted dialkyl ureas, taken from the literature.", "contents": "Solvent denaturation of globular proteins: unfolding by the monoalkyl- and dialkyl-substituted formamides and ureas. The effects of the monoalkyl and dialkyl-substituted formamide series of denaturants on the native conformation of sperm whale myoglobin, horse heart cytochrome c, and Glycera dibranciata (single chain) hemoglobin have been investigated by spectral measurements in the Soret region (409 and 422 nm) and optical rotation measurements (265nm). The effectiveness of these two classes of protein denaturants is similar to the other straight-chain compounds of the urea, amide, and alcohol classes, examined in previous investigations from our laboratory. Their denaturing effectiveness is found to increase with increasing chain length or hydrocarbon content of the substituent alkyl groups. Application of the Peller and Flory equation to the denaturation data of the formamides shows that both the polar and the nonpolar group contributions to the protein-denaturant interactions have to be taken into account in order to correctly predict the observed denaturation midpoints. Additivity of the hydrophobic, KH\u00f8, and the polar, Kp, group contributions to the binding constants, KB = nKH\u00f8 + Kp, with n = 1 or 2 for the mono- of the di-alkyl substituted denaturants gave best account of the experimental data. The KH\u00f8 values used were based on free energy transfer data of various alkyl groups or the Scheraga-Nemethy theory of hydrophobic bonding. The assumption of group contributions of the denaturant to KB were also applied to the denaturation data of the unsubstituted amides and some examples of the monoalkyl and symmetrically substituted dialkyl ureas, taken from the literature."}
{"id": "PMID:189824", "title": "Ligand-induced conformational changes in spin label-modified human hemoglobins and chains and their carboxypeptidase A-digested derivatives.", "content": "The reactive sulfhydryls of human adult and fetal hemoglobin and the single sulfhydryl of isolated gamma chains have been spin labeled with N-(1-oxyl-2,2,5,5-tetramethyl-3-pyrrolidinyl) iodoacetamide. Similar electron paramagnetic spectral differences between oxy- and deoxy-modified hemoglobins were observed for both these hemoglobins and for the isolated chains, indicating that ligand-induced conformational changes occur in isolated hemoglobin subunits as well as intact hemoglobin tetramers. Ligand induced changes in the reactivity of p-hydroxymercuribenzoate with the sulfhydryl groups of both intact hemoglobins and isolated subunits, observed by McDonald and Noble (1974) J. Biol. Chem. 249, 3161-3165), led them to draw a similar conclusion. Following carboxypeptidase A digestion of these modified hemoglobins and gamma chains, a procedure which specifically removes the two C-terminal residues of the beta or gamma chains, spectral differences between the liganded and unliganded spin-labeled derivatives still persisted. However, the magnitude of this difference was not only more reduced in the case of the hemoglobins than in that of the subunits but the spectra of both the oxy and deoxy derivatives of the hemoglobins were characteristic of the oxy derivative of a cooperative tetrameric hemoglobin. These findings support the premise that the COOH-terminal end of the beta or gamma chain contributes, although possibly to different extents, to the spectral differences exhibited by both the spin-labeled hemoglobins and chains.", "contents": "Ligand-induced conformational changes in spin label-modified human hemoglobins and chains and their carboxypeptidase A-digested derivatives. The reactive sulfhydryls of human adult and fetal hemoglobin and the single sulfhydryl of isolated gamma chains have been spin labeled with N-(1-oxyl-2,2,5,5-tetramethyl-3-pyrrolidinyl) iodoacetamide. Similar electron paramagnetic spectral differences between oxy- and deoxy-modified hemoglobins were observed for both these hemoglobins and for the isolated chains, indicating that ligand-induced conformational changes occur in isolated hemoglobin subunits as well as intact hemoglobin tetramers. Ligand induced changes in the reactivity of p-hydroxymercuribenzoate with the sulfhydryl groups of both intact hemoglobins and isolated subunits, observed by McDonald and Noble (1974) J. Biol. Chem. 249, 3161-3165), led them to draw a similar conclusion. Following carboxypeptidase A digestion of these modified hemoglobins and gamma chains, a procedure which specifically removes the two C-terminal residues of the beta or gamma chains, spectral differences between the liganded and unliganded spin-labeled derivatives still persisted. However, the magnitude of this difference was not only more reduced in the case of the hemoglobins than in that of the subunits but the spectra of both the oxy and deoxy derivatives of the hemoglobins were characteristic of the oxy derivative of a cooperative tetrameric hemoglobin. These findings support the premise that the COOH-terminal end of the beta or gamma chain contributes, although possibly to different extents, to the spectral differences exhibited by both the spin-labeled hemoglobins and chains."}
{"id": "PMID:189825", "title": "An EPR study of the lineshape of copper in cytochrome c oxidase.", "content": "The EPR spectrum of copper in cytochrome c oxidase (EC 1.9.3.1) has been studied between 5 and 220 degreesK, and the spectral parameters have been determined for both forms of EPR-detectable copper by computer simulation methods. Numerical methods have been developed to separate the spectra of intrinsic copper and inactive copper. Evidence is presented to show that inactive copper is probably formed by denaturation. The EPR parameters for intrinsic copper were determined as gx = 1.99, gy = 2.03, gz = 2.185, / Ax(Cu) / = 0.0020 cm-1, / Ay(Cu) / = 0.0025 cm-1, / Az(Cu) / = 0.0030 cm-1. The principal values of the g tensor and the small value of /Az(Cu) / are interpreted in terms of mixing of 3d, 4s, and 4p metal orbitals. A flattened-tetrahedral stereochemistry about Cu2+ with an additional rhombic distrotion is in best agreement with all of the data. The peak-to-peak linewidth is found to be orientation dependent, and is described by a tensor with principal values deltaHx = 45G, deltaHy = 65 G, deltaHz = 85 G. A weak dipolar interaction with a low-spin ferric species stereochemistry for the copper ion is consistent with the electron transport function of the enzyme. Broad EPR signals with a very short spin-lattice relaxation time has been observed near g = 14 and g = 3 at 5 degrees K in oxidized cytochrome oxidase but not in the reduced or denatured enzyme. The possibility that these are due to the \"EPR-undetectable\" iron and copper is raised.", "contents": "An EPR study of the lineshape of copper in cytochrome c oxidase. The EPR spectrum of copper in cytochrome c oxidase (EC 1.9.3.1) has been studied between 5 and 220 degreesK, and the spectral parameters have been determined for both forms of EPR-detectable copper by computer simulation methods. Numerical methods have been developed to separate the spectra of intrinsic copper and inactive copper. Evidence is presented to show that inactive copper is probably formed by denaturation. The EPR parameters for intrinsic copper were determined as gx = 1.99, gy = 2.03, gz = 2.185, / Ax(Cu) / = 0.0020 cm-1, / Ay(Cu) / = 0.0025 cm-1, / Az(Cu) / = 0.0030 cm-1. The principal values of the g tensor and the small value of /Az(Cu) / are interpreted in terms of mixing of 3d, 4s, and 4p metal orbitals. A flattened-tetrahedral stereochemistry about Cu2+ with an additional rhombic distrotion is in best agreement with all of the data. The peak-to-peak linewidth is found to be orientation dependent, and is described by a tensor with principal values deltaHx = 45G, deltaHy = 65 G, deltaHz = 85 G. A weak dipolar interaction with a low-spin ferric species stereochemistry for the copper ion is consistent with the electron transport function of the enzyme. Broad EPR signals with a very short spin-lattice relaxation time has been observed near g = 14 and g = 3 at 5 degrees K in oxidized cytochrome oxidase but not in the reduced or denatured enzyme. The possibility that these are due to the \"EPR-undetectable\" iron and copper is raised."}
{"id": "PMID:189826", "title": "The application of ESR to chromatin. Spin-labelling of the histone H3 cysteine residues in situ.", "content": "The possibility has been investigated of selectively spin-labelling the cysteine residues of histone H3 in chromatin and probing by ESR conformational changes affecting the labelled area as the molecular environment is altered. About 90% of bound labels are attached to the thiol groups and are strongly immobilized in deep crevices. The remaining labels are bound to amino groups mainly on histone H1, giving rise to a more mobile component in the chromatin spectrum. No conformational changes involving the labelled cysteins could be detected as the histones were dissociated stepwise from the complex by NaCl, but treatment with urea led to a cooperative increase in mobility, indicating that the hydrophobic region around the cysteine residues is folded in a compact tertiary structure to which histone H4 may be bound in the native complex, but which is not affected by dissociation of the H3-H4 unit from the DNA. In addition, chymotryptic disruption of the chromatin has been followed and an estimate made from the rotational correlation times of the size and origin of the digestion fragment carrying spin-labelled cysteine 110.", "contents": "The application of ESR to chromatin. Spin-labelling of the histone H3 cysteine residues in situ. The possibility has been investigated of selectively spin-labelling the cysteine residues of histone H3 in chromatin and probing by ESR conformational changes affecting the labelled area as the molecular environment is altered. About 90% of bound labels are attached to the thiol groups and are strongly immobilized in deep crevices. The remaining labels are bound to amino groups mainly on histone H1, giving rise to a more mobile component in the chromatin spectrum. No conformational changes involving the labelled cysteins could be detected as the histones were dissociated stepwise from the complex by NaCl, but treatment with urea led to a cooperative increase in mobility, indicating that the hydrophobic region around the cysteine residues is folded in a compact tertiary structure to which histone H4 may be bound in the native complex, but which is not affected by dissociation of the H3-H4 unit from the DNA. In addition, chymotryptic disruption of the chromatin has been followed and an estimate made from the rotational correlation times of the size and origin of the digestion fragment carrying spin-labelled cysteine 110."}
{"id": "PMID:189827", "title": "High resolution EPR studies of the fine structure of heme proteins. Third harmonic detection approach.", "content": "When third harmonic detection is applied in EPR studies of the superhyperfine structure of nitrosyl derivatives of a number of human hemoglobin variants, significant resoltuion enhancement is obtained. This has allowed a detailed analysis of the number of superhyperfine lines, their g-values and their splittings, and has led to a more complete understanding of the interaction between the axial ligands of the heme iron. Sudies of the effect of the modulation amplitude on EPR line-shapes revealed that the amplitude required to resolve fine structure in the third harmonic mode is 3-10 times larger than that used to record an undistorted first derivative spectrum. The application of this approach for other systems is discussed, and practical guidelines for its use are given.", "contents": "High resolution EPR studies of the fine structure of heme proteins. Third harmonic detection approach. When third harmonic detection is applied in EPR studies of the superhyperfine structure of nitrosyl derivatives of a number of human hemoglobin variants, significant resoltuion enhancement is obtained. This has allowed a detailed analysis of the number of superhyperfine lines, their g-values and their splittings, and has led to a more complete understanding of the interaction between the axial ligands of the heme iron. Sudies of the effect of the modulation amplitude on EPR line-shapes revealed that the amplitude required to resolve fine structure in the third harmonic mode is 3-10 times larger than that used to record an undistorted first derivative spectrum. The application of this approach for other systems is discussed, and practical guidelines for its use are given."}
{"id": "PMID:189828", "title": "Crossing of low-lying electronic levels of high-spin ferrous ion in deoxyhemoglobin and deoxymyoglobin.", "content": "The electronic structure of high-spin S = 2 ferrous ion in deoxy forms of hemoglobin and myoglobin is considered in terms of spin Hamiltonian formalism. Spin Hamiltonian parameters of the second order B0(2)(D), B2(2)(E) and, for the first time in the available literature, of fourth order B0(4), B2(4) and B4(4), are calculated for the rhombic symmetry case of Fe2+. The Hamiltonian matrix is diagonalized for several sets of Bq(k) parameters compatible with other experimental data. The low-lying Fe2+ levels exhibit crossings in a high magnetic field, applied along the z-axis perpendicular to the heme plane. The cross-over values of the magnetic field are determined to be Hc1 = 46 kOe and Hc2 = 168 kOe for D = 5.2, E = 0.6 cm-1 (close to the magnetic data of Nakano, N., Otsuka, J. and Tasaki, A. (1972) Biochim. Biophys. Acta 278, 355-371) and with B0(4) = 0.037, B2(4) = 0.005, B4(4) = 0.013 cm-1 and gz = 2.028. Experimental techniques for measurement of the crossing effects are discussed.", "contents": "Crossing of low-lying electronic levels of high-spin ferrous ion in deoxyhemoglobin and deoxymyoglobin. The electronic structure of high-spin S = 2 ferrous ion in deoxy forms of hemoglobin and myoglobin is considered in terms of spin Hamiltonian formalism. Spin Hamiltonian parameters of the second order B0(2)(D), B2(2)(E) and, for the first time in the available literature, of fourth order B0(4), B2(4) and B4(4), are calculated for the rhombic symmetry case of Fe2+. The Hamiltonian matrix is diagonalized for several sets of Bq(k) parameters compatible with other experimental data. The low-lying Fe2+ levels exhibit crossings in a high magnetic field, applied along the z-axis perpendicular to the heme plane. The cross-over values of the magnetic field are determined to be Hc1 = 46 kOe and Hc2 = 168 kOe for D = 5.2, E = 0.6 cm-1 (close to the magnetic data of Nakano, N., Otsuka, J. and Tasaki, A. (1972) Biochim. Biophys. Acta 278, 355-371) and with B0(4) = 0.037, B2(4) = 0.005, B4(4) = 0.013 cm-1 and gz = 2.028. Experimental techniques for measurement of the crossing effects are discussed."}
{"id": "PMID:189829", "title": "Spectroscopic studies of the oxidation-reduction properties of three forms of ferredoxin from Desulphovibrio gigas.", "content": "Electron paramagnetic resonance spectra were recorded of three forms of Desulphovibrio gigas ferredoxin, FdI, FdI' and FdII. The g = 1.94 signal seen in dithionite-reduced samples is strong in FdI, weaker in FdI' and very small in FdII. The g = 2.02 signal in the oxidized proteins is weak in FdI and strongest in FdII. It is concluded that most of the 4Fe-4S centres in FdI change between states C- and C2-; FdI' contain both types of centre. There is no evidence that any particular centre can change reversibly between all three oxidation states. Circular dichroism spectra show differences between FdI and FdII even in the diamagnetic C2- state. The redox potentials of the iron-sulphur centres of the three oligomers (forms) are different. After formation of the apo-protein of FdII and reconstitution with iron and sulphide, the protein behaves more like FdI, showing a strong g = 1.94 signal in the reduced states.", "contents": "Spectroscopic studies of the oxidation-reduction properties of three forms of ferredoxin from Desulphovibrio gigas. Electron paramagnetic resonance spectra were recorded of three forms of Desulphovibrio gigas ferredoxin, FdI, FdI' and FdII. The g = 1.94 signal seen in dithionite-reduced samples is strong in FdI, weaker in FdI' and very small in FdII. The g = 2.02 signal in the oxidized proteins is weak in FdI and strongest in FdII. It is concluded that most of the 4Fe-4S centres in FdI change between states C- and C2-; FdI' contain both types of centre. There is no evidence that any particular centre can change reversibly between all three oxidation states. Circular dichroism spectra show differences between FdI and FdII even in the diamagnetic C2- state. The redox potentials of the iron-sulphur centres of the three oligomers (forms) are different. After formation of the apo-protein of FdII and reconstitution with iron and sulphide, the protein behaves more like FdI, showing a strong g = 1.94 signal in the reduced states."}
{"id": "PMID:189830", "title": "Physical, chemical and immunochemical characterization of a lipoprotein lipase activator protein from pig plasma very low density lipoproteins.", "content": "Very low density lipoproteins ere isolated from plasma of swine by ultracentrifugal flotation. After delipidation, the lipid-free proteins were separated by chromatography on Sephadex G-150 AND DEAE-cellulose. A major apoprotein was isolated and shown to activate cows' milk lipoprotein lipase. Since human very low density lipoproteins also contain an activator protein, designated, apoC-II, we have called the pig protein, pig apoC-II. Pig apoC-II had a molecular weight of approximately 10 000 as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The amino acid composistion showed the absence of histidine, cysteine and tryptophan; there was no evidence for carbohydrate. Treatment of pig apoC-II with carboxypeptidase indicated COOH-terminal serine. Rabbit antisera prepared to the pig protein gave single precipitin lines of complete identity to very low density lipoproteins, apoC-11. Using anti-pig apoC-II, a radioimmunoassay was developed which provides a convenient and reproducible method for measuring 5-1000 ng of apoprotein.", "contents": "Physical, chemical and immunochemical characterization of a lipoprotein lipase activator protein from pig plasma very low density lipoproteins. Very low density lipoproteins ere isolated from plasma of swine by ultracentrifugal flotation. After delipidation, the lipid-free proteins were separated by chromatography on Sephadex G-150 AND DEAE-cellulose. A major apoprotein was isolated and shown to activate cows' milk lipoprotein lipase. Since human very low density lipoproteins also contain an activator protein, designated, apoC-II, we have called the pig protein, pig apoC-II. Pig apoC-II had a molecular weight of approximately 10 000 as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The amino acid composistion showed the absence of histidine, cysteine and tryptophan; there was no evidence for carbohydrate. Treatment of pig apoC-II with carboxypeptidase indicated COOH-terminal serine. Rabbit antisera prepared to the pig protein gave single precipitin lines of complete identity to very low density lipoproteins, apoC-11. Using anti-pig apoC-II, a radioimmunoassay was developed which provides a convenient and reproducible method for measuring 5-1000 ng of apoprotein."}
{"id": "PMID:189831", "title": "Chemical analysis of the hyphal wall of Schizophyllum commune.", "content": "1. Purified hyphal wall fragments of Schizophyllum commune are analysed and shown to consist of glucose (67.6%), mannose (3.4%), xylose (0.2%), (N-acetyl)glucosamine (12.5%), amino acids (6.4%) and some lipid material (3.0%). 2. The previously proposed structures of two glucans located at the hyphal wall surface (Wessels et al. (1972) Biochim. Biophys. Acta 273, 346-358) were essentially confirmed using methylation analysis. The mucilaginous glucan consists of 1,3-linked beta-glucan chains with branches of single glucose units attached by beta-1,6 linkages on every third unit, on average, along the chain. The alkali soluble S-glucan is an exclusively 1,3-linked alpha-glucan. 3. The alkali-insoluble R-glucan, occurring in close association with chitin, in the inner wall layer, has been characterised by methylation analysis, X-ray diffraction, enzymatic hydrolysis with purified exo-beta-1,3-glucanase and Smith degradation. It appears to be a highly branched beta-1,3,beta-1,6-glucan and a model of this glucan is proposed. Certain parts of this highly insoluble R-glucan bear a close structural similarity to the mucilaginous glucan present at the outer wall surface and in the medium.", "contents": "Chemical analysis of the hyphal wall of Schizophyllum commune. 1. Purified hyphal wall fragments of Schizophyllum commune are analysed and shown to consist of glucose (67.6%), mannose (3.4%), xylose (0.2%), (N-acetyl)glucosamine (12.5%), amino acids (6.4%) and some lipid material (3.0%). 2. The previously proposed structures of two glucans located at the hyphal wall surface (Wessels et al. (1972) Biochim. Biophys. Acta 273, 346-358) were essentially confirmed using methylation analysis. The mucilaginous glucan consists of 1,3-linked beta-glucan chains with branches of single glucose units attached by beta-1,6 linkages on every third unit, on average, along the chain. The alkali soluble S-glucan is an exclusively 1,3-linked alpha-glucan. 3. The alkali-insoluble R-glucan, occurring in close association with chitin, in the inner wall layer, has been characterised by methylation analysis, X-ray diffraction, enzymatic hydrolysis with purified exo-beta-1,3-glucanase and Smith degradation. It appears to be a highly branched beta-1,3,beta-1,6-glucan and a model of this glucan is proposed. Certain parts of this highly insoluble R-glucan bear a close structural similarity to the mucilaginous glucan present at the outer wall surface and in the medium."}
{"id": "PMID:189833", "title": "Rat pancreatic adenylate cyclase. IV. Effect of hormones and other agents on cyclic AMP level and enzyme release.", "content": "1. The effects of secretin and pancreozymin-C-octapeptide and phosphodiesterase inhibitors on the concentration of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and on the release of enzymes from rat pancreas have been studied. 2. In determininging cyclic AMP by means of the saturation assay of Brown et al. ((1971) Biochem. J. 121, 561-563) it is found essential to purify the pancreatic tissue extract by ion-exchange chromatography prior to the assay. 3. Injection of synthetic secretin or pancreozymin-C-octapeptide in anaesthetized rats in a secretory active dose (0.1 nmol) has no effect on the pancreatic cyclic AMP level. 4. Incubation for up to 10 min of pancreatic slices in Krebs-Ringer bicarbonate glucose medium containing 10(-2) M theophylline as phosphodiesterase inhibitor does not result in an increase of the cyclic AMP level. With 10(-2) M 1-methyl-3-isobutylxanthine as phosphodiesterase inhibitor the level is more than doubled after the first min of incubation and remains constant thereafter. 5. Addition of 3-10(-7) M secretin to slices incubated in the presence of 10(-2) M theophylline causes 84% increase of the cyclic AMP level above control, whereas the addition of 3-10(-7) M pancreozymin-C-octapeptide has no significant effect. In the presence of 10(-2) M 1-methyl-3-isobutylxanthine the latter hormone causes significant increases of up to 34% above control during 10 min of incubation. Secretin in this condition augments the cyclic AMP level by up to 296% above control during a 10 min incubation period. Addition of secretin  and pancreozymin-C-octapeptide together has no greater effect than of secretin alone. 6. A broken cell fraction of rat pancreas contains adenylate cyclase activity which can be stimulated to 457 and 600% above the basal activity by 3-10(-7) M pancreozymin-C-octapeptide and secretin, respectively. Incubation of pancreatic slices with either hormone has no effect on the cyclic AMP phosphodiesterase activity in the homogenate of these slices. 7. Pancreozymin-C-octapeptide, dibutyryl cyclic AMP, 1-methyl-3-isobutylxanthine and carbamylcholine cause an elevated release of chymotrypsin from pancreatic slices incubated for 2 h in Krebs-Ringer bicarbonate medium, containing 10 mM glucose, while secretin, cyclic AMP and butyric acid have no significant effect. The release of the cytoplasmic enzyme lactate dehydrogenase is also elevated by dibutyryl cyclic AMP, 1-methyl-3-isobutylxanthine and carbamylcholine, but not significantly by pancreozymin-C-octapeptide. 8. The results support the role of cyclic AMP in the action of secretin, and do not exclude a mediating function of this nucleotide in the actions of pancreozymin in rat pancreas.", "contents": "Rat pancreatic adenylate cyclase. IV. Effect of hormones and other agents on cyclic AMP level and enzyme release. 1. The effects of secretin and pancreozymin-C-octapeptide and phosphodiesterase inhibitors on the concentration of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and on the release of enzymes from rat pancreas have been studied. 2. In determininging cyclic AMP by means of the saturation assay of Brown et al. ((1971) Biochem. J. 121, 561-563) it is found essential to purify the pancreatic tissue extract by ion-exchange chromatography prior to the assay. 3. Injection of synthetic secretin or pancreozymin-C-octapeptide in anaesthetized rats in a secretory active dose (0.1 nmol) has no effect on the pancreatic cyclic AMP level. 4. Incubation for up to 10 min of pancreatic slices in Krebs-Ringer bicarbonate glucose medium containing 10(-2) M theophylline as phosphodiesterase inhibitor does not result in an increase of the cyclic AMP level. With 10(-2) M 1-methyl-3-isobutylxanthine as phosphodiesterase inhibitor the level is more than doubled after the first min of incubation and remains constant thereafter. 5. Addition of 3-10(-7) M secretin to slices incubated in the presence of 10(-2) M theophylline causes 84% increase of the cyclic AMP level above control, whereas the addition of 3-10(-7) M pancreozymin-C-octapeptide has no significant effect. In the presence of 10(-2) M 1-methyl-3-isobutylxanthine the latter hormone causes significant increases of up to 34% above control during 10 min of incubation. Secretin in this condition augments the cyclic AMP level by up to 296% above control during a 10 min incubation period. Addition of secretin  and pancreozymin-C-octapeptide together has no greater effect than of secretin alone. 6. A broken cell fraction of rat pancreas contains adenylate cyclase activity which can be stimulated to 457 and 600% above the basal activity by 3-10(-7) M pancreozymin-C-octapeptide and secretin, respectively. Incubation of pancreatic slices with either hormone has no effect on the cyclic AMP phosphodiesterase activity in the homogenate of these slices. 7. Pancreozymin-C-octapeptide, dibutyryl cyclic AMP, 1-methyl-3-isobutylxanthine and carbamylcholine cause an elevated release of chymotrypsin from pancreatic slices incubated for 2 h in Krebs-Ringer bicarbonate medium, containing 10 mM glucose, while secretin, cyclic AMP and butyric acid have no significant effect. The release of the cytoplasmic enzyme lactate dehydrogenase is also elevated by dibutyryl cyclic AMP, 1-methyl-3-isobutylxanthine and carbamylcholine, but not significantly by pancreozymin-C-octapeptide. 8. The results support the role of cyclic AMP in the action of secretin, and do not exclude a mediating function of this nucleotide in the actions of pancreozymin in rat pancreas."}
{"id": "PMID:189834", "title": "Insulin-sensitive adenosine 3',5'-cyclic monophosphate phosphodiesterase of hepatocyte plasma membrane.", "content": "Adenosine 3',5'-cyclic monophosphate phosphodiesterase (EC 3.1.4.17) has been investigated in rat liver as to its insulin sensitivity. Hormone action has been assayed in vitro on a liver homogenate purified by DEAE-cellulose column chromatography, on isolated hepatocytes, on isolated plasma membranes. The DEAE-cellulose chromatography purified homogenate showed no sensitivity to insulin, whereas isolated hepatocytes incubated in presence of insulin showed increased phosphodiesterase activity in a plasma membrane-containing fraction. The plasma membrane-bound enzyme, which shows both high and low affinity components, was significantly stimulated after hormonal treatment; this effect being dependent on a V increase of the low Km form.", "contents": "Insulin-sensitive adenosine 3',5'-cyclic monophosphate phosphodiesterase of hepatocyte plasma membrane. Adenosine 3',5'-cyclic monophosphate phosphodiesterase (EC 3.1.4.17) has been investigated in rat liver as to its insulin sensitivity. Hormone action has been assayed in vitro on a liver homogenate purified by DEAE-cellulose column chromatography, on isolated hepatocytes, on isolated plasma membranes. The DEAE-cellulose chromatography purified homogenate showed no sensitivity to insulin, whereas isolated hepatocytes incubated in presence of insulin showed increased phosphodiesterase activity in a plasma membrane-containing fraction. The plasma membrane-bound enzyme, which shows both high and low affinity components, was significantly stimulated after hormonal treatment; this effect being dependent on a V increase of the low Km form."}
{"id": "PMID:189835", "title": "Effect of diabetes and insulin on rat renal glomerular protocollagen hydroxylase activities.", "content": "The effect of diabetes and insulin on the activities of both prolyl hydroxylase (trivial name; proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) and lysyl hydroxylase (trivial name; lysine,2-oxoglutarate dioxygenase, EC 1.14.11.4) in isolated rat renal glomeruli was determined. Three groups of experimental animals were used: age-matched controls, streptozotocin-diabetic, and insulin-treated streptozotocin-diabetic. Using 14C-labeled lysine or proline hydroxylase substrate prepared from chick embryo tibiae, glomerular 17 000 X g supernatant enzyme was incubated in a complete hydroxylating system for 60 and 120 min Lysyl hydroxylase activity was significantly increased in diabetic preparations, but prolyl hydroxylase activity did not differ from control. Administration of insulin to streptozotocin-injected animals completely restored glomerular lysyl hydroxylase to normal levels. The results suggest that the specific elevation of lysyl hydroxylase relates to the biochemical changes contributory to diabetic nephropathy, and that insulin may reverse this process.", "contents": "Effect of diabetes and insulin on rat renal glomerular protocollagen hydroxylase activities. The effect of diabetes and insulin on the activities of both prolyl hydroxylase (trivial name; proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) and lysyl hydroxylase (trivial name; lysine,2-oxoglutarate dioxygenase, EC 1.14.11.4) in isolated rat renal glomeruli was determined. Three groups of experimental animals were used: age-matched controls, streptozotocin-diabetic, and insulin-treated streptozotocin-diabetic. Using 14C-labeled lysine or proline hydroxylase substrate prepared from chick embryo tibiae, glomerular 17 000 X g supernatant enzyme was incubated in a complete hydroxylating system for 60 and 120 min Lysyl hydroxylase activity was significantly increased in diabetic preparations, but prolyl hydroxylase activity did not differ from control. Administration of insulin to streptozotocin-injected animals completely restored glomerular lysyl hydroxylase to normal levels. The results suggest that the specific elevation of lysyl hydroxylase relates to the biochemical changes contributory to diabetic nephropathy, and that insulin may reverse this process."}
{"id": "PMID:189836", "title": "Studies on the mechanisms of epinephrine stimulation of lypolysis.", "content": "The time course for epinephrine stimulation of lypolysis, cyclic AMP accumulation and activation of protein kinase was studied in adipose tissue from hypophysectomized rats. Triglyceride breakdown, as assessed by glycerol release, increased rapidly in response to epinephrine, maintained a constant rate as long as the hormone was present, and decreased rapidly to basal values when the hormone was removed. Cyclic AMP accumulation was transient peaking within 3 min of exposure to epinephrine and then declining to levels indistinguishable from basal by 9 min. Protein kinase activity in extracts also peaked at 3 min and thereafter declined to a level approximately 25% greater than resting activity. Peak levels of cyclic AMP, steady state levels of protein kinase activity and the rate of glycerol production were all related in a dose dependent manner to the concentration of epinephrine. These observations suggest that the spike in cyclic AMP levels may be necessary to trigger the activation of lipolysis, but was not sufficient to sustain an accelerated rate of triglyceride breakdown. Continued activation of protein kinase, however, may be essential to sustained lipolysis.", "contents": "Studies on the mechanisms of epinephrine stimulation of lypolysis. The time course for epinephrine stimulation of lypolysis, cyclic AMP accumulation and activation of protein kinase was studied in adipose tissue from hypophysectomized rats. Triglyceride breakdown, as assessed by glycerol release, increased rapidly in response to epinephrine, maintained a constant rate as long as the hormone was present, and decreased rapidly to basal values when the hormone was removed. Cyclic AMP accumulation was transient peaking within 3 min of exposure to epinephrine and then declining to levels indistinguishable from basal by 9 min. Protein kinase activity in extracts also peaked at 3 min and thereafter declined to a level approximately 25% greater than resting activity. Peak levels of cyclic AMP, steady state levels of protein kinase activity and the rate of glycerol production were all related in a dose dependent manner to the concentration of epinephrine. These observations suggest that the spike in cyclic AMP levels may be necessary to trigger the activation of lipolysis, but was not sufficient to sustain an accelerated rate of triglyceride breakdown. Continued activation of protein kinase, however, may be essential to sustained lipolysis."}
{"id": "PMID:189837", "title": "Preparation and characterization of specifically tritiated adrenocorticotropin.", "content": "The catalytic dehalogenation of iodinated derivatives of corticotropin in the presence of tritium was investigated. In 0.1 M acetic acid, complete and rapid removal of iodine was achieved in the presence of freshly prepared palladium or palladium oxide as catalyst, but the specific radioactivity of the product was only 10-20% of the theoretically attainable value. Synthetic human corticotropin containing a 3,5-diiodo tyrosine in position 23 in place of tyrosine was successfully dehalogenated in solvent mixture 0.1 M acetic acid: hexamethylphosphoramide: dimethylformamide (1 : 10 : 90, v/v) in the presence of palladium oxide and calcium carbonate. The product was obtained in 30% yield after purification by carboxymethyl cellulose chromatography. The tritiated hormone had a specific radioactivity of 46 Ci/mmol (80% of the theoretical value) and was as potent as synthetic human corticotropin in stimulating steroidogenesis and lipolysis.", "contents": "Preparation and characterization of specifically tritiated adrenocorticotropin. The catalytic dehalogenation of iodinated derivatives of corticotropin in the presence of tritium was investigated. In 0.1 M acetic acid, complete and rapid removal of iodine was achieved in the presence of freshly prepared palladium or palladium oxide as catalyst, but the specific radioactivity of the product was only 10-20% of the theoretically attainable value. Synthetic human corticotropin containing a 3,5-diiodo tyrosine in position 23 in place of tyrosine was successfully dehalogenated in solvent mixture 0.1 M acetic acid: hexamethylphosphoramide: dimethylformamide (1 : 10 : 90, v/v) in the presence of palladium oxide and calcium carbonate. The product was obtained in 30% yield after purification by carboxymethyl cellulose chromatography. The tritiated hormone had a specific radioactivity of 46 Ci/mmol (80% of the theoretical value) and was as potent as synthetic human corticotropin in stimulating steroidogenesis and lipolysis."}
{"id": "PMID:189838", "title": "On the role of cyclic AMP and cyclic GMP in steroid production by bovine cortical cells.", "content": "The time course of corticotropin-induced steroidogenesis and changes in intracellular cyclic AMP and cyclic GMP levels were investigated in isolated bovine adrenocortical cells prepared by trypsin digestion. Corticotropin produced a peak rise in cyclic AMP during the first 5 min of stimulation and enhanced steroid production after 15 min. Corticotropin also caused a decrease in cortical cyclic GMP at 5 min; this decrease in cyclic GMP reverted to a 2-3 fold increase at 15-30 min which gradually subsided by 60 min. A steroidogenic concentration of prostaglandin E2 also produced an elevation in the levels of both nucleotides, but the rise in cyclic GMP preceded the rise in cyclic AMP. These results suggest that the relative amounts of cyclic AMP and cyclic GMP, rather than the absolute levels of cyclic AMP, may be a key factor in the regulation of steroidogenesis.", "contents": "On the role of cyclic AMP and cyclic GMP in steroid production by bovine cortical cells. The time course of corticotropin-induced steroidogenesis and changes in intracellular cyclic AMP and cyclic GMP levels were investigated in isolated bovine adrenocortical cells prepared by trypsin digestion. Corticotropin produced a peak rise in cyclic AMP during the first 5 min of stimulation and enhanced steroid production after 15 min. Corticotropin also caused a decrease in cortical cyclic GMP at 5 min; this decrease in cyclic GMP reverted to a 2-3 fold increase at 15-30 min which gradually subsided by 60 min. A steroidogenic concentration of prostaglandin E2 also produced an elevation in the levels of both nucleotides, but the rise in cyclic GMP preceded the rise in cyclic AMP. These results suggest that the relative amounts of cyclic AMP and cyclic GMP, rather than the absolute levels of cyclic AMP, may be a key factor in the regulation of steroidogenesis."}
{"id": "PMID:189839", "title": "Evidence for nuclear and DNA binding forms of the receptor-glucocorticoid complex from hepatoma tissue culture cells.", "content": "Binding to DNA associated with cellulose has been used to investigate the receptor-glucocorticoid complex isolated from a line of rat hepatoma tissue culture cells. The amount of activated complex that bound to DNA was approximately half that which bound to nuclei. Additional results suggest the existence of two forms of the activated glucocorticoid receptor-steroid complex in about equal amounts: one form binds only to nuclei and the other binds to DNA and nuclei. The two forms also differ in their stability, with the DNA/nuclei binging form being relatively labile. The binding of either form to the appropriate acceptor is reduced by cytosol inhibitors by the same mechanism.", "contents": "Evidence for nuclear and DNA binding forms of the receptor-glucocorticoid complex from hepatoma tissue culture cells. Binding to DNA associated with cellulose has been used to investigate the receptor-glucocorticoid complex isolated from a line of rat hepatoma tissue culture cells. The amount of activated complex that bound to DNA was approximately half that which bound to nuclei. Additional results suggest the existence of two forms of the activated glucocorticoid receptor-steroid complex in about equal amounts: one form binds only to nuclei and the other binds to DNA and nuclei. The two forms also differ in their stability, with the DNA/nuclei binging form being relatively labile. The binding of either form to the appropriate acceptor is reduced by cytosol inhibitors by the same mechanism."}
{"id": "PMID:189840", "title": "Glucocorticoid receptor-steroid complex binding to DNA. Competition between DNA and DNA-cellulose.", "content": "The binding of the glucocorticoid receptor-steroid complex from a line of rat hepatoma tissue culture (HTC) cells to DNA has been examined. An equilibrium competition assay involving a constant, low total amount of double-stranded DNA was developed to compare the complex binding ability of DNA free in solution and bound to cellulose. This binding ability is lowered by a factor of five when DNA is associated with cellulose. Similar studies with HTC cell, calf-thymus, and Escherichia coli DNA revealed no difference in the relative number or affinity of binding sites for receptor-steroid complex in each DNA. The synthetic DNA molecules poly[d(A-T)-d(A-T)] and poly[d(G-C)-d(G-C)] bound complexes equally well but less than the three \"natural\" DNA molecules. This appears to be due to differences in acceptor site affinity and suggests that nucleotide complexity and/or sequence influences the affinity of HTC cell receptor-glucocorticoid complexes for DNA.", "contents": "Glucocorticoid receptor-steroid complex binding to DNA. Competition between DNA and DNA-cellulose. The binding of the glucocorticoid receptor-steroid complex from a line of rat hepatoma tissue culture (HTC) cells to DNA has been examined. An equilibrium competition assay involving a constant, low total amount of double-stranded DNA was developed to compare the complex binding ability of DNA free in solution and bound to cellulose. This binding ability is lowered by a factor of five when DNA is associated with cellulose. Similar studies with HTC cell, calf-thymus, and Escherichia coli DNA revealed no difference in the relative number or affinity of binding sites for receptor-steroid complex in each DNA. The synthetic DNA molecules poly[d(A-T)-d(A-T)] and poly[d(G-C)-d(G-C)] bound complexes equally well but less than the three \"natural\" DNA molecules. This appears to be due to differences in acceptor site affinity and suggests that nucleotide complexity and/or sequence influences the affinity of HTC cell receptor-glucocorticoid complexes for DNA."}
{"id": "PMID:189841", "title": "Immunoassay for honey bee cytochrome c in single animals with cytochrome c-coated bacteriophages: a sensitive tool for the study of caste formation in the honey bee, Apis mellifera.", "content": "The development of a sensitive viroimmunoassay for honey bee cytochrome c and its usage for early detection of caste differentiation is described. Pure honey bee cytochrome c was isolated from workers and used to produce antibodies in rabbits. Bacteriophage T4 was chemically modified by covalent attachment of honey bee cytochrome c using tolylene-2,4-diisocyanate as a cross-linking agent. The immunospecific inactivation of this bacteriophage-cytochrome c conjugate by anti-cytochrome c antibodies can be inhibited by free cytochrome c. In quantitative determinations, 50% inhibition is reproducibly achieved at a concentration of 6 ng/ml (5 pmol/ml) and as little as 0.3 ng/ml (0.25 pmol/ml) could be detected by this system. Cytochrome c concentrations were measured in individual animals and substantial differences corresponding larval stages of worker and queen bees are reported.", "contents": "Immunoassay for honey bee cytochrome c in single animals with cytochrome c-coated bacteriophages: a sensitive tool for the study of caste formation in the honey bee, Apis mellifera. The development of a sensitive viroimmunoassay for honey bee cytochrome c and its usage for early detection of caste differentiation is described. Pure honey bee cytochrome c was isolated from workers and used to produce antibodies in rabbits. Bacteriophage T4 was chemically modified by covalent attachment of honey bee cytochrome c using tolylene-2,4-diisocyanate as a cross-linking agent. The immunospecific inactivation of this bacteriophage-cytochrome c conjugate by anti-cytochrome c antibodies can be inhibited by free cytochrome c. In quantitative determinations, 50% inhibition is reproducibly achieved at a concentration of 6 ng/ml (5 pmol/ml) and as little as 0.3 ng/ml (0.25 pmol/ml) could be detected by this system. Cytochrome c concentrations were measured in individual animals and substantial differences corresponding larval stages of worker and queen bees are reported."}
{"id": "PMID:189842", "title": "Genetic evidence for the common identity of glucose-6-phosphatase, pyrophosphate-glucose phosphotransferase, carbamyl phosphate-glucose phosphotransferase and inorganic pyrophosphatase.", "content": "We demonstrate that glucose-6-phosphatase, pyrophosphate-glucose phosphotransferase, carbamyl phosphate-glucose phosphotransferase and inorganic pyrophosphatase activities are deficient in livers of patients with type I glycogen storage disease. This provides strong genetic evidence that these enzymatic activities reside in a single protein or share a common polypeptide chain.", "contents": "Genetic evidence for the common identity of glucose-6-phosphatase, pyrophosphate-glucose phosphotransferase, carbamyl phosphate-glucose phosphotransferase and inorganic pyrophosphatase. We demonstrate that glucose-6-phosphatase, pyrophosphate-glucose phosphotransferase, carbamyl phosphate-glucose phosphotransferase and inorganic pyrophosphatase activities are deficient in livers of patients with type I glycogen storage disease. This provides strong genetic evidence that these enzymatic activities reside in a single protein or share a common polypeptide chain."}
{"id": "PMID:189843", "title": "Effect of metabolites and phosphorylase on the D to I conversion of glycogen synthase from human polymorphonuclear leukocytes.", "content": "The D to I conversion of glycogen synthase from human polymorphonuclear leukocytes was examined both in a gel-filtered homogenate and in a preparation of glycogen particles with adhering enzymes, purified by chromatography on concanavalin A bound to Sepharose. It was found that glucose 6-phosphate as well as mannose 6-phosphate, glucosamine 6-phosphate, and 2-deoxy-glucose 6-phosphate activated the reaction, whereas the corresponding sugars were without effect. Mn2+ and Ca2+ increased the conversion rate by 51% and 27%, respectively, whereas Mg2+ and inorganic phosphate were without effect. Sodium fluoride inhibited the reaction completely. Glycogen inhibited the reaction in physiological concentrations and 0.5 mM glucose 6-phosphate was able to overcome this inhibition. MgATP greatly augmented the inhibition caused by glycogen in the glycogen particle preparation. This combined effect could be overcome by glucose 6-phosphate in concentrations from 0.1 to 1 mM. Phosphorylase alpha purified from human polymorphonuclear leukocytes inhibited the D to I conversion in a glycogen particle preparation. The inhibition was counteracted by glucose 6-phosphate and to a lesser degree by AMP. Phosphorylase beta was also inhibitory, but only at higher concentrations than phosphorylase alpha. No phosphorylase phosphatase activity was found in the glycogen particle preparation, which may indicate that chromatography on concanavalin A-Sepharose separates this enzyme from the synthase phosphatase or partially destroys the activity of a hypothetical common protein phosphatase.", "contents": "Effect of metabolites and phosphorylase on the D to I conversion of glycogen synthase from human polymorphonuclear leukocytes. The D to I conversion of glycogen synthase from human polymorphonuclear leukocytes was examined both in a gel-filtered homogenate and in a preparation of glycogen particles with adhering enzymes, purified by chromatography on concanavalin A bound to Sepharose. It was found that glucose 6-phosphate as well as mannose 6-phosphate, glucosamine 6-phosphate, and 2-deoxy-glucose 6-phosphate activated the reaction, whereas the corresponding sugars were without effect. Mn2+ and Ca2+ increased the conversion rate by 51% and 27%, respectively, whereas Mg2+ and inorganic phosphate were without effect. Sodium fluoride inhibited the reaction completely. Glycogen inhibited the reaction in physiological concentrations and 0.5 mM glucose 6-phosphate was able to overcome this inhibition. MgATP greatly augmented the inhibition caused by glycogen in the glycogen particle preparation. This combined effect could be overcome by glucose 6-phosphate in concentrations from 0.1 to 1 mM. Phosphorylase alpha purified from human polymorphonuclear leukocytes inhibited the D to I conversion in a glycogen particle preparation. The inhibition was counteracted by glucose 6-phosphate and to a lesser degree by AMP. Phosphorylase beta was also inhibitory, but only at higher concentrations than phosphorylase alpha. No phosphorylase phosphatase activity was found in the glycogen particle preparation, which may indicate that chromatography on concanavalin A-Sepharose separates this enzyme from the synthase phosphatase or partially destroys the activity of a hypothetical common protein phosphatase."}
{"id": "PMID:189844", "title": "On the role of calcium as second messenger in liver for the hormonally induced activation of glycogen phosphorylase.", "content": "We have studied the mode of action of three hormones (angiotensin, vasopressin and phenylephrine, an alpha-adrenergic agent) which promote liver glycogenolysis in a cyclic AMP-independent way, in comparison with that of glucagon, which is known to act essentially via cyclic AMP. The following observations were made using isolated rat hepatocytes: (a) In the normal Krebs-Henseleit bicarbonate medium, the hormones activated glycogen phosphorylase (EC 2.4.1.1) to about the same degree. In contrast to glucagon, the cyclic AMP-independent hormones did not activate either protein kinase (EC 2.7.1.37) or phosphorylase b kinase (EC 2.7.1.38). (b) The absence of Ca2+ from the incubation medium prevented the activation of glycogen phosphorylase by the cyclic AMP-independent agents and slowed down that induced by glucagon. (c) The ionophore A 23187 produced the same degree of activation of glycogen phosphorylase, provided that Ca2+ was present in the incubation medium. (d) Glucagon, cyclic AMP and three cyclic AMP-dependent hormones caused an enhanced uptake of 45Ca; it was verified that concentrations of angiotensin and of vasopressin known to occur in haemorrhagic conditions were able to produce phosphorylase activation and stimulate 45Ca uptake. (e) Appropriate antagonists (i.e. phentolamine against phenylephrine and an angiotensin analogue against angiotensin) prevented both the enhanced 45Ca uptake and the phosphorylase activation. We interpret our data in favour of a role of calcium (1) as the second messenger in liver for the three cyclic AMP-independent glycogenolytic hormones and (2) as an additional messenger for glucagon which, via cyclic AMP, will make calcium available to the cytoplasm either from extracellular or from intracellular pools. The target enzyme for Ca2+ is most probably phosphorylase b kinase.", "contents": "On the role of calcium as second messenger in liver for the hormonally induced activation of glycogen phosphorylase. We have studied the mode of action of three hormones (angiotensin, vasopressin and phenylephrine, an alpha-adrenergic agent) which promote liver glycogenolysis in a cyclic AMP-independent way, in comparison with that of glucagon, which is known to act essentially via cyclic AMP. The following observations were made using isolated rat hepatocytes: (a) In the normal Krebs-Henseleit bicarbonate medium, the hormones activated glycogen phosphorylase (EC 2.4.1.1) to about the same degree. In contrast to glucagon, the cyclic AMP-independent hormones did not activate either protein kinase (EC 2.7.1.37) or phosphorylase b kinase (EC 2.7.1.38). (b) The absence of Ca2+ from the incubation medium prevented the activation of glycogen phosphorylase by the cyclic AMP-independent agents and slowed down that induced by glucagon. (c) The ionophore A 23187 produced the same degree of activation of glycogen phosphorylase, provided that Ca2+ was present in the incubation medium. (d) Glucagon, cyclic AMP and three cyclic AMP-dependent hormones caused an enhanced uptake of 45Ca; it was verified that concentrations of angiotensin and of vasopressin known to occur in haemorrhagic conditions were able to produce phosphorylase activation and stimulate 45Ca uptake. (e) Appropriate antagonists (i.e. phentolamine against phenylephrine and an angiotensin analogue against angiotensin) prevented both the enhanced 45Ca uptake and the phosphorylase activation. We interpret our data in favour of a role of calcium (1) as the second messenger in liver for the three cyclic AMP-independent glycogenolytic hormones and (2) as an additional messenger for glucagon which, via cyclic AMP, will make calcium available to the cytoplasm either from extracellular or from intracellular pools. The target enzyme for Ca2+ is most probably phosphorylase b kinase."}
{"id": "PMID:189845", "title": "Characterization of lipolytic responses of isolated white adipocytes from hamsters.", "content": "1. Lipolysis by isolated white adipocytes from hamsters, as measured by glycerol production, was stimulated by corticotropin, isopropylnorepinephrine (INE), norepinephrine, or epinephrine (EPI), in a dose-dependent fashion. 2. Lipolysis was stimulated by five inhibitors of cyclic 3',5'-adenosine monophosphate phosphodiesterase: caffeine, theophylline, 1-methyl-3-isobutyl xanthine, 1-ethyl-4-(isopropylidenehydrazine)-1H-pyrazolo-(3,4,-b)-pyridine-5-carboxylic acid ethyl ester (SQ 20009), and 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro 7-2956). Caffeine-stimulated lipolysis consistently attained higher rates than did hormone-stimulated lipolysis. However, when cells were stimulated by both caffeine and a hormone, lipolytic rates were consistently lower than those attained under the influence of caffeine alone. 3. Isolated white adipocytes from hamsters were sensitive to both alpha- and beta-adrenergic antagonists. The beta-adrenergic antagonist propranolol could completely inhibit norepinephrine-stimulated glycerol production. The alpha-adrenergic antagonist phentolamine, on the other hand, had a biphasic effect on the cells. At 5-10(-7) M or 5-10(-6) M, phentolamine enhanced norepinephrine-stimulated lipolysis, while concentrations higher than 5-10(-5) M caused inhibition. 4. The effects of two different concentrations of six antilipolytic agents, prostaglandin E1, nicotinic acid, phenylisopropyladenosine, 5-methylpyrazole-3-carboxylic acid, adenosine and insulin, were measured. With the exception of insulin, all of these agents showed much more potent inhibition of caffeine-stimulated lipolysis than of hormone-stimulated lipolysis. Insulin, in contrast, showed only modest inhibition of hormone-stimulated lipolysis and virtually no inhibition of caffeine-stimulated lipolysis.", "contents": "Characterization of lipolytic responses of isolated white adipocytes from hamsters. 1. Lipolysis by isolated white adipocytes from hamsters, as measured by glycerol production, was stimulated by corticotropin, isopropylnorepinephrine (INE), norepinephrine, or epinephrine (EPI), in a dose-dependent fashion. 2. Lipolysis was stimulated by five inhibitors of cyclic 3',5'-adenosine monophosphate phosphodiesterase: caffeine, theophylline, 1-methyl-3-isobutyl xanthine, 1-ethyl-4-(isopropylidenehydrazine)-1H-pyrazolo-(3,4,-b)-pyridine-5-carboxylic acid ethyl ester (SQ 20009), and 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro 7-2956). Caffeine-stimulated lipolysis consistently attained higher rates than did hormone-stimulated lipolysis. However, when cells were stimulated by both caffeine and a hormone, lipolytic rates were consistently lower than those attained under the influence of caffeine alone. 3. Isolated white adipocytes from hamsters were sensitive to both alpha- and beta-adrenergic antagonists. The beta-adrenergic antagonist propranolol could completely inhibit norepinephrine-stimulated glycerol production. The alpha-adrenergic antagonist phentolamine, on the other hand, had a biphasic effect on the cells. At 5-10(-7) M or 5-10(-6) M, phentolamine enhanced norepinephrine-stimulated lipolysis, while concentrations higher than 5-10(-5) M caused inhibition. 4. The effects of two different concentrations of six antilipolytic agents, prostaglandin E1, nicotinic acid, phenylisopropyladenosine, 5-methylpyrazole-3-carboxylic acid, adenosine and insulin, were measured. With the exception of insulin, all of these agents showed much more potent inhibition of caffeine-stimulated lipolysis than of hormone-stimulated lipolysis. Insulin, in contrast, showed only modest inhibition of hormone-stimulated lipolysis and virtually no inhibition of caffeine-stimulated lipolysis."}
{"id": "PMID:189846", "title": "Rat pancreas adenylate cyclase V. Its presence in isolated rat pancreatic acinar cells.", "content": "(1) In order to determine the cellular localization of the secretin- and pancreozymin-sensitive adenylate cyclase in rat pancreas, the occurence of this enzyme system has been investigated in isolated pancreatic cells. (2) Digestion of rat pancreatic lobules with collagenase yields a preparation of isolated cells which upon differential morphological analysis appears to consist for 97% of acinar cells and to contain for fewer centro-acinar and ductal cells than undissociated lobules. (3) Expressed per mg protein, the isolated cells contain the same amount of DNA, chymotrypsin and lactic dehydrogenase as the undissociated tissue. The stimulated adenylate cyclase activity is nearly entirely recovered in the isolated acinar cells, as is also the case for the low Km adenosine 3',5-cyclic monophosphate phosphodiesterase activity and the adenosine 3',5'-cyclic monophosphate (cyclic AMP) content. Marked losses are noted for the basal adenylate cyclase and the high Km cyclic AMP phosphodiesterase activities. (4) Washing the isolated acinar cells in Krebs-Ringer bicarbonate medium containing 10 mM 1-methyl-3-isobutylxanthine causes a cyclic AMP level 2.6 times that in cells washed in Krebs-Ringer bicarbonate alone. The cyclic AMP level is further increased by subsequently incubating the cells for 10 min in the presence of 3-10(-7) M pancreozymin-C-octapeptide or secretin to values 1.7 or 4.7 times the control level in cells incubated for 10 min with 1-methyl-3-isobutylxanthine alone. (5) It is suggested that the adenylate cyclase of the acinar cells may be involved, with another factor, in the stimulation of enzyme secretion, whereas a ductular cyclase would function in the regulation of the bicarbonate-dependent fluid secretion.", "contents": "Rat pancreas adenylate cyclase V. Its presence in isolated rat pancreatic acinar cells. (1) In order to determine the cellular localization of the secretin- and pancreozymin-sensitive adenylate cyclase in rat pancreas, the occurence of this enzyme system has been investigated in isolated pancreatic cells. (2) Digestion of rat pancreatic lobules with collagenase yields a preparation of isolated cells which upon differential morphological analysis appears to consist for 97% of acinar cells and to contain for fewer centro-acinar and ductal cells than undissociated lobules. (3) Expressed per mg protein, the isolated cells contain the same amount of DNA, chymotrypsin and lactic dehydrogenase as the undissociated tissue. The stimulated adenylate cyclase activity is nearly entirely recovered in the isolated acinar cells, as is also the case for the low Km adenosine 3',5-cyclic monophosphate phosphodiesterase activity and the adenosine 3',5'-cyclic monophosphate (cyclic AMP) content. Marked losses are noted for the basal adenylate cyclase and the high Km cyclic AMP phosphodiesterase activities. (4) Washing the isolated acinar cells in Krebs-Ringer bicarbonate medium containing 10 mM 1-methyl-3-isobutylxanthine causes a cyclic AMP level 2.6 times that in cells washed in Krebs-Ringer bicarbonate alone. The cyclic AMP level is further increased by subsequently incubating the cells for 10 min in the presence of 3-10(-7) M pancreozymin-C-octapeptide or secretin to values 1.7 or 4.7 times the control level in cells incubated for 10 min with 1-methyl-3-isobutylxanthine alone. (5) It is suggested that the adenylate cyclase of the acinar cells may be involved, with another factor, in the stimulation of enzyme secretion, whereas a ductular cyclase would function in the regulation of the bicarbonate-dependent fluid secretion."}
{"id": "PMID:189847", "title": "On the requirement for protein synthesis during corticotropin-induced stimulation of cholesterol side chain cleavage in rat adrenal mitochondrial and solubilized desmolase preparations.", "content": "Following simple homogenization, significant amounts of mitochondrial-derived, cholesterol side chain cleaving enzyme (desmolase) activity are recovered in rat adrenal 105 000 X g-supernatant fraction. Corticotropin administration enhances soluble desmolase activity, and cycloheximide potentiates this effect. The lipid droplet fraction which has no desmolase activity markedly enhances pregnenolone synthesis in the soluble desmolase preparations, presumably by supplying free cholesterol substrate. Corticotropin particularly with cycloheximide pretreatment, enhances lipid fraction activity. Thus increased cholesterol availability may largely explain the corticotropin effect on the soluble desmolase system. Since protein synthesis is required for corticotropin activity in intact mitochondria, but not in calcium-swollen mitochondria or the soluble enzyme system, the labile protein apparently required during corticotropin action may function to overcome a \"barrier\" which exists only in the intact mitochondria and restrains cholesterol side chain cleavage.", "contents": "On the requirement for protein synthesis during corticotropin-induced stimulation of cholesterol side chain cleavage in rat adrenal mitochondrial and solubilized desmolase preparations. Following simple homogenization, significant amounts of mitochondrial-derived, cholesterol side chain cleaving enzyme (desmolase) activity are recovered in rat adrenal 105 000 X g-supernatant fraction. Corticotropin administration enhances soluble desmolase activity, and cycloheximide potentiates this effect. The lipid droplet fraction which has no desmolase activity markedly enhances pregnenolone synthesis in the soluble desmolase preparations, presumably by supplying free cholesterol substrate. Corticotropin particularly with cycloheximide pretreatment, enhances lipid fraction activity. Thus increased cholesterol availability may largely explain the corticotropin effect on the soluble desmolase system. Since protein synthesis is required for corticotropin activity in intact mitochondria, but not in calcium-swollen mitochondria or the soluble enzyme system, the labile protein apparently required during corticotropin action may function to overcome a \"barrier\" which exists only in the intact mitochondria and restrains cholesterol side chain cleavage."}
{"id": "PMID:189852", "title": "Detection of immediate early, early and late antigens in herpes simplex virus type 1 infected cells.", "content": "Immediate early, early and late antigens synthesized in herpes simplex virus (HSV) type 1 infected cells can be efficiently demonstrated using the sensitive anti-complement immunofluorescence (ACIF) test and highly specific antisera prepared against early or late HSV-1 determined proteins in a syngeneic rat system.", "contents": "Detection of immediate early, early and late antigens in herpes simplex virus type 1 infected cells. Immediate early, early and late antigens synthesized in herpes simplex virus (HSV) type 1 infected cells can be efficiently demonstrated using the sensitive anti-complement immunofluorescence (ACIF) test and highly specific antisera prepared against early or late HSV-1 determined proteins in a syngeneic rat system."}
{"id": "PMID:189854", "title": "The thermal polymerization of amino acids in the presence of sand.", "content": "Sand was tested as a model of a common \"impurity\" that could have influenced the formation of thermal prebiotic protein. Increasing proportions of sand (0-16 g) in admixture with one set of reactant amino acids (1g), when heated at 175 degrees C for 1.5 h, resulted in increasing yields of polyamino acids of increasing size and color intensity; amino acid composition was not greatly affected. Similar results were noted for three of five other sets of reactant amino acids (8 g sand per g amino acids). In no case did sand prevent the amino acids from polymerizing. The results are interpreted to indicate a broader range of conditions conducive to the formation of prebiotic protein and to further emphasize that environmental parameters should be considerided in the experimental modeling of prebiotic processes.", "contents": "The thermal polymerization of amino acids in the presence of sand. Sand was tested as a model of a common \"impurity\" that could have influenced the formation of thermal prebiotic protein. Increasing proportions of sand (0-16 g) in admixture with one set of reactant amino acids (1g), when heated at 175 degrees C for 1.5 h, resulted in increasing yields of polyamino acids of increasing size and color intensity; amino acid composition was not greatly affected. Similar results were noted for three of five other sets of reactant amino acids (8 g sand per g amino acids). In no case did sand prevent the amino acids from polymerizing. The results are interpreted to indicate a broader range of conditions conducive to the formation of prebiotic protein and to further emphasize that environmental parameters should be considerided in the experimental modeling of prebiotic processes."}
{"id": "PMID:189853", "title": "Biophysics with nitroxyl radicals.", "content": "The present status of the spin labeling method as applied to Biophysics is examined. After an outline of the chemical and physical properties of NO radicals, the analysis of linear and non-linear ESR spectra of spin labels and the information it yields is described. The possibilities of the method are critically discussed in the light of recent experiments.", "contents": "Biophysics with nitroxyl radicals. The present status of the spin labeling method as applied to Biophysics is examined. After an outline of the chemical and physical properties of NO radicals, the analysis of linear and non-linear ESR spectra of spin labels and the information it yields is described. The possibilities of the method are critically discussed in the light of recent experiments."}
{"id": "PMID:189855", "title": "[Changes in the electrical activity of the cerebral cortex under the combined influence of Cl. perfringens type A toxin and products of Cl. butyricum activity].", "content": "A study of the changes of the electrocorticogram (ECoG) and the electrocardiogram (ECG) in combined action of Cl. perfringens, type A, and of the Cl. butyricum broth culture filtrate showed that desynchronization of the cortical electrical activity and its subsequent depression occurred at earlier periods than in the case of isolated administration of Cl. perfringens toxin. The general character of the changes in the cortical rhythmic activity remained the same as in intoxication caused by Cl. butyricum toxin alone. The ECoG and ECG changes occurred at shorter intervals. Cl. butyricum filtrates induced no ECoG and ECG changes. It is supposed that the effect of the products of the Cl. butyricum vital activity consisted in increase in the tissue barrier permeability and, in this connection, in a greater penetration of Cl. perfringens toxin into the tissues, including the central nervous system.", "contents": "[Changes in the electrical activity of the cerebral cortex under the combined influence of Cl. perfringens type A toxin and products of Cl. butyricum activity]. A study of the changes of the electrocorticogram (ECoG) and the electrocardiogram (ECG) in combined action of Cl. perfringens, type A, and of the Cl. butyricum broth culture filtrate showed that desynchronization of the cortical electrical activity and its subsequent depression occurred at earlier periods than in the case of isolated administration of Cl. perfringens toxin. The general character of the changes in the cortical rhythmic activity remained the same as in intoxication caused by Cl. butyricum toxin alone. The ECoG and ECG changes occurred at shorter intervals. Cl. butyricum filtrates induced no ECoG and ECG changes. It is supposed that the effect of the products of the Cl. butyricum vital activity consisted in increase in the tissue barrier permeability and, in this connection, in a greater penetration of Cl. perfringens toxin into the tissues, including the central nervous system."}
{"id": "PMID:189856", "title": "[Fractional composition of cytoplasmic RNP-particles in the cells of Zajdela ascitic hepatoma and the liver of a tumor-bearing animal].", "content": "The relative content of poly(A)-RNA in the cytoplasm was greater in the cells of Zajdela hepatoma and the liver of tumour-bearing rats than in the normal hepatocytes of rats. Besides, the tumour cells (and to a lesser extent the hepatocytes of the tumour-bearing animal) were characterized by the changes in the ratio of the polyribosomes and monoribosomes usual for normal hepatocytes (and correspondingly between the m-RNP-particles and the informosomes) in favour of the latter, this pointing to definite changes in their protein-synthesizing apparatus. As judged by some of the parameters, the cells of the tumour-bearing by some of the parameters, the cells of the tumour-bearing animal occupied an intermediate position between the normal and tumour cells.", "contents": "[Fractional composition of cytoplasmic RNP-particles in the cells of Zajdela ascitic hepatoma and the liver of a tumor-bearing animal]. The relative content of poly(A)-RNA in the cytoplasm was greater in the cells of Zajdela hepatoma and the liver of tumour-bearing rats than in the normal hepatocytes of rats. Besides, the tumour cells (and to a lesser extent the hepatocytes of the tumour-bearing animal) were characterized by the changes in the ratio of the polyribosomes and monoribosomes usual for normal hepatocytes (and correspondingly between the m-RNP-particles and the informosomes) in favour of the latter, this pointing to definite changes in their protein-synthesizing apparatus. As judged by some of the parameters, the cells of the tumour-bearing by some of the parameters, the cells of the tumour-bearing animal occupied an intermediate position between the normal and tumour cells."}
{"id": "PMID:189857", "title": "[Effect of adrenoreceptor blockaders on the mitotic activity of regenerating liver].", "content": "One hour before resection of the liver and repeatedly 24 hours after the operation male rats were given phentholamine--a blocker of alpha-adrenoceptors; this preparation inhibited the mitotic activity of the regenerating liver. A double administration at the same periods of propanol--a blocker of beta-adrenoceptors--caused an elevation of the mitotic activity. A conclusion was drawn that by stimulation of beta-adrenoceptors it was possible to inhibit the regenerative process. Adrenaline stimulated this process by acting through beta-adrenoceptors.", "contents": "[Effect of adrenoreceptor blockaders on the mitotic activity of regenerating liver]. One hour before resection of the liver and repeatedly 24 hours after the operation male rats were given phentholamine--a blocker of alpha-adrenoceptors; this preparation inhibited the mitotic activity of the regenerating liver. A double administration at the same periods of propanol--a blocker of beta-adrenoceptors--caused an elevation of the mitotic activity. A conclusion was drawn that by stimulation of beta-adrenoceptors it was possible to inhibit the regenerative process. Adrenaline stimulated this process by acting through beta-adrenoceptors."}
{"id": "PMID:189859", "title": "Hydrogen peroxide production and killing of Staphylococcus aureus by human polymorphonuclear leukocytes.", "content": "The effects of bacterial neuraminidase on production of hydrogen peroxide (H2O2) and killing of Staphylococcus aureus by human polymorphonuclear leukocytes (PMN) were studied. The concentration of H2O2 was measured by the disappearance of scopoletin fluorescence in the presence of horseradish peroxidase. The results indicated that desialylation of human PMN inhibited the stimulation of H2O2 production during phagocytosis. It also markedly impaired the killing of S. aureus. Impaired killing of S. aureus by desialylated PMN was due to impaired intracellular killing rather than defective phagocytosis.", "contents": "Hydrogen peroxide production and killing of Staphylococcus aureus by human polymorphonuclear leukocytes. The effects of bacterial neuraminidase on production of hydrogen peroxide (H2O2) and killing of Staphylococcus aureus by human polymorphonuclear leukocytes (PMN) were studied. The concentration of H2O2 was measured by the disappearance of scopoletin fluorescence in the presence of horseradish peroxidase. The results indicated that desialylation of human PMN inhibited the stimulation of H2O2 production during phagocytosis. It also markedly impaired the killing of S. aureus. Impaired killing of S. aureus by desialylated PMN was due to impaired intracellular killing rather than defective phagocytosis."}
{"id": "PMID:189860", "title": "Cyclic AMP and protein kinase in the spontaneously hypertensive rat aorta and tissue-cultured aortic smooth muscle cells.", "content": "Cyclic AMP levels and protein kinase activity were determined in the aortas of rats with normotension, moderate and severe spontaneous hypertension. While the cyclic AMP levels were reduced in the aortas from rats with moderate and sever hypertension the protein kinase levels were found to be elevated only in the aortas from rats with severe hypertension. We have grown in tissue culture, aortic smooth muscle cells from the normotensive and severely hypertensive rat. Cultured cells from both strains have similar growth patterns and morphology. The differences seen in cyclic AMP  and protein kinase levels in the intact aortas are also seen in the aortic smooth muscle cells in cluture.", "contents": "Cyclic AMP and protein kinase in the spontaneously hypertensive rat aorta and tissue-cultured aortic smooth muscle cells. Cyclic AMP levels and protein kinase activity were determined in the aortas of rats with normotension, moderate and severe spontaneous hypertension. While the cyclic AMP levels were reduced in the aortas from rats with moderate and sever hypertension the protein kinase levels were found to be elevated only in the aortas from rats with severe hypertension. We have grown in tissue culture, aortic smooth muscle cells from the normotensive and severely hypertensive rat. Cultured cells from both strains have similar growth patterns and morphology. The differences seen in cyclic AMP  and protein kinase levels in the intact aortas are also seen in the aortic smooth muscle cells in cluture."}
{"id": "PMID:189861", "title": "Vascular adenylate cyclase: role of age and guanine nucleotide activation.", "content": "Particulate adenylate cyclase activity was examined in broken cell preparations of rat aorta and mesenteric artery from 3- to 5- and 9- to 13-week-old rats. While basal adenylate cyclase activity of the mesenteric artery was 4-fold greater than aortic enzyme activity, there was no difference in enzyme activity with age. GTP and the GTP analogue, 5'-guanylylimidodiphosphate [Gpp(NH)p] stimulated adenylate cyclase activity. Stimulation by Gpp(NH)p did not differ with age for either tissue and occurred without a detectable lag. The vasodilators, isoproterenol, 2-chloroadenosine and prostaglandin E1, were ineffective in increasing adenylate cyclase activity, although marked stimulation was demonstrated with both sodium fluoride and Gpp(NH)p. Even in combination with Gpp(NH)p, isoproterenol did not increase particulate adenylate cyclase activity of these blood vessels; however, with intact arteries, isoproterenol (10(-7)M) did increase aortic and mesenteric cyclic AMP levels. Isoproterenol increased cyclic AMP levels in rats of both ages, at a time when isoproterenol was less effective in maximally relaxing aortic strips from 9- to 13-week-old rats. These data indicate that diminished aortic relaxation with age is not associated with a reduced ability of vascular relaxants to increase aortic cyclic AMP levels. Furthermore, as a first step in establishing that guanine nucleotides are regulators of vascular adenylate cyclase, both GTP and Gpp(NH)p were found to be potent activators of adenylate cyclase from blood vessels.", "contents": "Vascular adenylate cyclase: role of age and guanine nucleotide activation. Particulate adenylate cyclase activity was examined in broken cell preparations of rat aorta and mesenteric artery from 3- to 5- and 9- to 13-week-old rats. While basal adenylate cyclase activity of the mesenteric artery was 4-fold greater than aortic enzyme activity, there was no difference in enzyme activity with age. GTP and the GTP analogue, 5'-guanylylimidodiphosphate [Gpp(NH)p] stimulated adenylate cyclase activity. Stimulation by Gpp(NH)p did not differ with age for either tissue and occurred without a detectable lag. The vasodilators, isoproterenol, 2-chloroadenosine and prostaglandin E1, were ineffective in increasing adenylate cyclase activity, although marked stimulation was demonstrated with both sodium fluoride and Gpp(NH)p. Even in combination with Gpp(NH)p, isoproterenol did not increase particulate adenylate cyclase activity of these blood vessels; however, with intact arteries, isoproterenol (10(-7)M) did increase aortic and mesenteric cyclic AMP levels. Isoproterenol increased cyclic AMP levels in rats of both ages, at a time when isoproterenol was less effective in maximally relaxing aortic strips from 9- to 13-week-old rats. These data indicate that diminished aortic relaxation with age is not associated with a reduced ability of vascular relaxants to increase aortic cyclic AMP levels. Furthermore, as a first step in establishing that guanine nucleotides are regulators of vascular adenylate cyclase, both GTP and Gpp(NH)p were found to be potent activators of adenylate cyclase from blood vessels."}
{"id": "PMID:189862", "title": "Ca++-binding properties of cznine aortic microsomes: lack of effect of c-AMP.", "content": "Ca++-binding to a microsomal fraction canine aorta has been studied and compared to Ca++-binding to canine cardiac microsomes. The aortic microsomes bound up to 60 nmoles Ca++/mg protein with a first-order binding rate constant of 0.025 sec-1. The binding rate of 5 sec was about half that of cardiac microsomes, 8 versus 15 nmoles/mg. The Ca++-binding to the aortic microsomes had a pH optimum of 7.4, was inhibited by monovalent cations and showed ATP preference when compared to other nucleotides. The binding was not stimulated by the presence of oxalate. c-AMP stimulated incorporation of 32P into the preparation, but had no effect on Ca++-binding.", "contents": "Ca++-binding properties of cznine aortic microsomes: lack of effect of c-AMP. Ca++-binding to a microsomal fraction canine aorta has been studied and compared to Ca++-binding to canine cardiac microsomes. The aortic microsomes bound up to 60 nmoles Ca++/mg protein with a first-order binding rate constant of 0.025 sec-1. The binding rate of 5 sec was about half that of cardiac microsomes, 8 versus 15 nmoles/mg. The Ca++-binding to the aortic microsomes had a pH optimum of 7.4, was inhibited by monovalent cations and showed ATP preference when compared to other nucleotides. The binding was not stimulated by the presence of oxalate. c-AMP stimulated incorporation of 32P into the preparation, but had no effect on Ca++-binding."}
{"id": "PMID:189863", "title": "[Importance of acidophilic fine granulation cells in the corticotropic activity of the adenohypophysis].", "content": "The cyto-immunological tests prove that anti-ACTH (17-39) immunserums do not become localized only on beta cells of anterior lobe of Man's pituitary. They can also react upon cells with slender erythrosinophilic granules. Normally, these cells are very scattered. However, we have established that they were particulary numerous in the pituitary of six infants suddendly deceased. Conspicuously, these cells with acidophilic granulations correspond to a stage of corticotropic cells maturation.", "contents": "[Importance of acidophilic fine granulation cells in the corticotropic activity of the adenohypophysis]. The cyto-immunological tests prove that anti-ACTH (17-39) immunserums do not become localized only on beta cells of anterior lobe of Man's pituitary. They can also react upon cells with slender erythrosinophilic granules. Normally, these cells are very scattered. However, we have established that they were particulary numerous in the pituitary of six infants suddendly deceased. Conspicuously, these cells with acidophilic granulations correspond to a stage of corticotropic cells maturation."}
{"id": "PMID:189864", "title": "[Modification of the number and structure of certain cytoplasmic components of the renal tubules during compensatory hypertrophy].", "content": "In the remaining kidney of unilaterally nephrectomised three to six months old Wistar rats, the measurement of the external and internal diameters indicated an increase in size of both proximal and distal convoluted tubules, although less distinct in the latter. Stereomorphometric measurements of the chondriome and the cytoplasmic inclusions (lysosomes, phagosomes, peroxisomes, etc.) have shown, as compared with similar tests in shamoperated animals, changes in the volumes of these components which can be related to the increase of enzymatic activities reported earlier. However, no obvious changes of the general ultrastructure of the kidneys undergoing hypertrophy could be observed.", "contents": "[Modification of the number and structure of certain cytoplasmic components of the renal tubules during compensatory hypertrophy]. In the remaining kidney of unilaterally nephrectomised three to six months old Wistar rats, the measurement of the external and internal diameters indicated an increase in size of both proximal and distal convoluted tubules, although less distinct in the latter. Stereomorphometric measurements of the chondriome and the cytoplasmic inclusions (lysosomes, phagosomes, peroxisomes, etc.) have shown, as compared with similar tests in shamoperated animals, changes in the volumes of these components which can be related to the increase of enzymatic activities reported earlier. However, no obvious changes of the general ultrastructure of the kidneys undergoing hypertrophy could be observed."}
{"id": "PMID:189870", "title": "Pulmonary metabolism of bradykinin analogues and the contribution of angiotensin converting enzyme to bradykinin inactivation in isolated lungs.", "content": "1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of both analogues on guinea-pig ileum was potentiated (2.5-3.0 fold) by a bradykinin potentiating peptide (BPP9a) but less so than the action of bradykinin (4-5 fold). 4 Like bradykinin, the 8-homo Phe analogue was extensively inactivated (greater than 90%) in a single passage through the pulmonary circulation of guinea-pig or rat isolated lungs and this inactivation was prevented by pre-treatment of the lungs with BPP9a. 5 The 7-homo Pro analogue was inactivated to a lesser degree in guinea-pig lungs (58%) and in rat lungs (89%) and its inactivation was not affected by BPP9a. 6 It is concluded that the 8-homo Phe analogue is a substrate for the dipeptidylcarboxypeptidase (angiotensin I converting enzyme) of lung, whereas the 7-homo Pro analogue is not a substrate. 7 There is about four times as much dipeptidylcarboxypeptidase activity in guinea-pig isolated lungs as there is in rat isolated lungs.", "contents": "Pulmonary metabolism of bradykinin analogues and the contribution of angiotensin converting enzyme to bradykinin inactivation in isolated lungs. 1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of both analogues on guinea-pig ileum was potentiated (2.5-3.0 fold) by a bradykinin potentiating peptide (BPP9a) but less so than the action of bradykinin (4-5 fold). 4 Like bradykinin, the 8-homo Phe analogue was extensively inactivated (greater than 90%) in a single passage through the pulmonary circulation of guinea-pig or rat isolated lungs and this inactivation was prevented by pre-treatment of the lungs with BPP9a. 5 The 7-homo Pro analogue was inactivated to a lesser degree in guinea-pig lungs (58%) and in rat lungs (89%) and its inactivation was not affected by BPP9a. 6 It is concluded that the 8-homo Phe analogue is a substrate for the dipeptidylcarboxypeptidase (angiotensin I converting enzyme) of lung, whereas the 7-homo Pro analogue is not a substrate. 7 There is about four times as much dipeptidylcarboxypeptidase activity in guinea-pig isolated lungs as there is in rat isolated lungs."}
{"id": "PMID:189867", "title": "[Plasma lipids in respiratory insufficiency: relation with hypercapnia and hypoxaemia (author's transl)].", "content": "A study of plasma lipids in a group of 111 patients with chronic lung disease has been carried out and compared with a reference group of 37 normal subjects. In decompensated patients, a decrease in beta-lipoproteins, cholesterol, triglycerids, total lipids, and in the beta-lipoproteins cholesterol/total cholesterol ratio (Cb-Ct) was observed. These changes were not in correlation with PaCO2 values, neither with the presence or absence of cor pulmonale, but seemed to be related with the degree of hypoxaemia. The distribution of patients in two groups according to PaO2 (below or above 50 mmHg) revealed statistically significant difference. The follow-up of 23 of these patients showed a good correlation of clinical evolution with dyslipemia.", "contents": "[Plasma lipids in respiratory insufficiency: relation with hypercapnia and hypoxaemia (author's transl)]. A study of plasma lipids in a group of 111 patients with chronic lung disease has been carried out and compared with a reference group of 37 normal subjects. In decompensated patients, a decrease in beta-lipoproteins, cholesterol, triglycerids, total lipids, and in the beta-lipoproteins cholesterol/total cholesterol ratio (Cb-Ct) was observed. These changes were not in correlation with PaCO2 values, neither with the presence or absence of cor pulmonale, but seemed to be related with the degree of hypoxaemia. The distribution of patients in two groups according to PaO2 (below or above 50 mmHg) revealed statistically significant difference. The follow-up of 23 of these patients showed a good correlation of clinical evolution with dyslipemia."}
{"id": "PMID:189871", "title": "Structure-activity relationship of various corticosteroids on the feedback control of corticotrophin secretion.", "content": "Several steroids occurring in the pathway of corticosteroid biosynthesis were investigated for their ability to exert a fast or delayed feedback inhibition of stress-induced release of corticotrophin. Rats were injected subcutaneously with vehicle or a steroid either 10 min (fast feedback) or 4 h (delayed feedback) before they were subjected to stress which consisted of a 2 min exposure to ether vapour. 2 Changes in plasma corticosterone concentration and in vitro corticosterone production by excised adrenal glands were used as indices of corticotrophin release. 3 Among the steroids tested only 11beta, 21-dihydroxypregn-4-ene-3, 20-dione (corticosterone) and 11beta, 17alpha, 21-trihydroxypregn-4-ene-3, 20-dione (cortisol) inhibited the stress response 10 min after their administration. Therefore, it appears that the fast feedback mechanism is limited to steroids with a 21-hydroxyl and a 11beta-hydroxyl group. 4 In contrast, many steroids caused inhibition of the stress response 4 h after their administration. These steroids were corticosterone, cortisol, 21-hydroxypregn-4-ene-3, 20-dione (11-deoxycorticosterone), 17alpha, 21-dihydroxypregn-4-ene-3, 20-dione (11-deoxycortisol), 11beta-hydroxypregn-4-ene-3, 20-dione (11beta-hydroxyprogesterone) and 11beta, 17alpha-dihydroxypregn-4-ene-3, 20-dione (11beta, 17alpha-dihydroxyprogesterone). Thus, either the 21-hydroxyl group (e.g. 11-deoxycorticosterone) or the 11beta-hydroxyl group (e.g. 11beta-hydroxyprogesterone) is sufficient for delayed feedback activity. The 11alpha-hydroxyl group, e.g. 11alpha, 17alpha, 21-trihydroxypregn-4-ene-3, 20-dione (11-epicortisol) renders the steroid inactive on both feedback mechanisms. 5 18,21-Dihydroxypregn-4-ene-3, 20-dione (18-hydroxydeoxycorticosterone) was found to be the only steroid that is secreted by the adrenal gland of the rat in quantities sufficient to cause exaggeration of the stress-induced release of corticotrophin. This steroid has been implicated as a possible hypertensive agent, and its role in the control of corticotrophin secretion is discussed here.", "contents": "Structure-activity relationship of various corticosteroids on the feedback control of corticotrophin secretion. Several steroids occurring in the pathway of corticosteroid biosynthesis were investigated for their ability to exert a fast or delayed feedback inhibition of stress-induced release of corticotrophin. Rats were injected subcutaneously with vehicle or a steroid either 10 min (fast feedback) or 4 h (delayed feedback) before they were subjected to stress which consisted of a 2 min exposure to ether vapour. 2 Changes in plasma corticosterone concentration and in vitro corticosterone production by excised adrenal glands were used as indices of corticotrophin release. 3 Among the steroids tested only 11beta, 21-dihydroxypregn-4-ene-3, 20-dione (corticosterone) and 11beta, 17alpha, 21-trihydroxypregn-4-ene-3, 20-dione (cortisol) inhibited the stress response 10 min after their administration. Therefore, it appears that the fast feedback mechanism is limited to steroids with a 21-hydroxyl and a 11beta-hydroxyl group. 4 In contrast, many steroids caused inhibition of the stress response 4 h after their administration. These steroids were corticosterone, cortisol, 21-hydroxypregn-4-ene-3, 20-dione (11-deoxycorticosterone), 17alpha, 21-dihydroxypregn-4-ene-3, 20-dione (11-deoxycortisol), 11beta-hydroxypregn-4-ene-3, 20-dione (11beta-hydroxyprogesterone) and 11beta, 17alpha-dihydroxypregn-4-ene-3, 20-dione (11beta, 17alpha-dihydroxyprogesterone). Thus, either the 21-hydroxyl group (e.g. 11-deoxycorticosterone) or the 11beta-hydroxyl group (e.g. 11beta-hydroxyprogesterone) is sufficient for delayed feedback activity. The 11alpha-hydroxyl group, e.g. 11alpha, 17alpha, 21-trihydroxypregn-4-ene-3, 20-dione (11-epicortisol) renders the steroid inactive on both feedback mechanisms. 5 18,21-Dihydroxypregn-4-ene-3, 20-dione (18-hydroxydeoxycorticosterone) was found to be the only steroid that is secreted by the adrenal gland of the rat in quantities sufficient to cause exaggeration of the stress-induced release of corticotrophin. This steroid has been implicated as a possible hypertensive agent, and its role in the control of corticotrophin secretion is discussed here."}
{"id": "PMID:189868", "title": "In vitro effect of insulin and adrenaline on lung triglyceride-lipase activity in rats.", "content": "The in vitro effect of insulin and adrenaline on the activity of lung triglyceride-lipases (alkaline and acid) has been investigated. Insulin inhibited strongly both triglyceride-lipases. Only caffein almost eliminated the inhibitory action of insulin, while adrenaline and dibutyryl cyclic adenosine monophosphate did not exhibit such an effect. It was assumed that the inhibition of lung triglyceride-lipases by insulin was effected through the activation of phosphodiesterases. On the other hand since adrenaline markedly activated lung triglyceride-lipases, this action was assumed to be carried out via the activation of lung adenylate cyclase and the increase of cyclic adenosine monophosphate.", "contents": "In vitro effect of insulin and adrenaline on lung triglyceride-lipase activity in rats. The in vitro effect of insulin and adrenaline on the activity of lung triglyceride-lipases (alkaline and acid) has been investigated. Insulin inhibited strongly both triglyceride-lipases. Only caffein almost eliminated the inhibitory action of insulin, while adrenaline and dibutyryl cyclic adenosine monophosphate did not exhibit such an effect. It was assumed that the inhibition of lung triglyceride-lipases by insulin was effected through the activation of phosphodiesterases. On the other hand since adrenaline markedly activated lung triglyceride-lipases, this action was assumed to be carried out via the activation of lung adenylate cyclase and the increase of cyclic adenosine monophosphate."}
{"id": "PMID:189872", "title": "Dopamine-induced neurogenic vaso-dilatation in the intact hindleg of the dog.", "content": "1 The dopamine-induced neurogenic vasodilation, previously described in the isolated perfused hindleg of the dog, has been studied in anaesthetized dogs with intact circulation in the hindleg. Dopamine was administered intravenously and/or intra-aortically, either as a bolus injection of 4 or 1l mug/kg, or as a continuous infusion of 4, 8, 16 or 32 mug kg-1 min-1. 2 Dopamine, given as a bolus injection or by infusion reversibly inhibited synaptic transmission in the paravertebral lumbar ganglia, studied with preganglionic stimulation at 1Hz. The inhibitory effect decreased gradually when the frequency of stimulation was increased to 16 Hz. The inhibition by dopamine was also present when spontaneous postganglionic activity was recorded. These effects were more pronounced on intra-aortic than on intravenous administration of dopamine. 3 In about half of the animals studied, injection or infusion of dopamine elicited a decrease of vascular resistance in the innervated femoral artery, whereas systemic blood pressure either did not change or decreased. In the denervated femoral artery, an increase in vascular resistance was alway observed. 4 The decrease in femoral vascular resistance was considered to correspond with neurogenic vasodilation caused by paravertebral ganglionic inhibition since (i) it only occurred in the innervated hindleg, (ii) blood pressure did not rise, (iii) this decrease was insensitive to atropine or propranolol and (iv) it was blocked by small doses of haloperidol. When hypovolemic shock was produced, the incidence of the neurogenic decrease of vascular resistance was smaller. 5 Dopamine also increased renal blood flow. This increase was not reduced by the occurrence of the neurogenic vasodilation in the inervated femoral artery. 6 These results are consistent with the idea that the dopamine-induced neurogenic vasodilation, originally described in the isolated perfused hindleg of the dog, also occurs when the circulation to the hindleg is intact. This suggests that, in the dog, also occurs when the circulation to the hindleg is intact. This suggests that, in the dog. the inhibitory effect of dopamine on sympathetic ganglia modulates its peripheral vasoconstrictor effects. In hypovolemic shock, where sympathetic nervous activity is high, the inhibitory effect of dopamine on sympathetic ganglia disappears and its direct vasoconstrictor effect on the vessels dominates.", "contents": "Dopamine-induced neurogenic vaso-dilatation in the intact hindleg of the dog. 1 The dopamine-induced neurogenic vasodilation, previously described in the isolated perfused hindleg of the dog, has been studied in anaesthetized dogs with intact circulation in the hindleg. Dopamine was administered intravenously and/or intra-aortically, either as a bolus injection of 4 or 1l mug/kg, or as a continuous infusion of 4, 8, 16 or 32 mug kg-1 min-1. 2 Dopamine, given as a bolus injection or by infusion reversibly inhibited synaptic transmission in the paravertebral lumbar ganglia, studied with preganglionic stimulation at 1Hz. The inhibitory effect decreased gradually when the frequency of stimulation was increased to 16 Hz. The inhibition by dopamine was also present when spontaneous postganglionic activity was recorded. These effects were more pronounced on intra-aortic than on intravenous administration of dopamine. 3 In about half of the animals studied, injection or infusion of dopamine elicited a decrease of vascular resistance in the innervated femoral artery, whereas systemic blood pressure either did not change or decreased. In the denervated femoral artery, an increase in vascular resistance was alway observed. 4 The decrease in femoral vascular resistance was considered to correspond with neurogenic vasodilation caused by paravertebral ganglionic inhibition since (i) it only occurred in the innervated hindleg, (ii) blood pressure did not rise, (iii) this decrease was insensitive to atropine or propranolol and (iv) it was blocked by small doses of haloperidol. When hypovolemic shock was produced, the incidence of the neurogenic decrease of vascular resistance was smaller. 5 Dopamine also increased renal blood flow. This increase was not reduced by the occurrence of the neurogenic vasodilation in the inervated femoral artery. 6 These results are consistent with the idea that the dopamine-induced neurogenic vasodilation, originally described in the isolated perfused hindleg of the dog, also occurs when the circulation to the hindleg is intact. This suggests that, in the dog, also occurs when the circulation to the hindleg is intact. This suggests that, in the dog. the inhibitory effect of dopamine on sympathetic ganglia modulates its peripheral vasoconstrictor effects. In hypovolemic shock, where sympathetic nervous activity is high, the inhibitory effect of dopamine on sympathetic ganglia disappears and its direct vasoconstrictor effect on the vessels dominates."}
{"id": "PMID:189873", "title": "A possible role for cyclic adenosine 3',5'-monophosphate in the regulation of acid secretion in the isolated stomach of guinea-pig.", "content": "1 The rate of acid secretion and mucosal cyclic adenosine 3',5'-monophosphate (cyclic AMP) content have been measured on the same guinea-pig isolated stomach preparation in response to histamine, theophylline and ICI 63197, a potent phosphodiesterase inhibitor. 2 Unstimulated control tissues had a spontaneous rate of acid secretion of 74.41 +/- 9.06 mumol H+/g wet wt. of mucosa per hour (s.e. mean, n = 20) and a cyclic AMP content of 0.517 +/- 0.058 mnol/g wet weight. 3 Each of the three drugs caused an increase in both the mucosal cyclic AMP content and the rate of acid secretion. These increases were inearly related to the logarithm of drug concentration for each drug. 4 There were no statistically significant differences between the three regression coefficients obtained for acid on drug and for cyclic AMP on drug. 5 There was a significant correlation between the rate of acid secretion and mucosal cyclic AMP content in stimulated preparations (P less than 0.001) and also in control preparations which received no drug (P less than 0.05). 6 These results are discussed in relation to the possible role of cyclic AMP in the mediation of acid secretory responses in the mammalian stomach.", "contents": "A possible role for cyclic adenosine 3',5'-monophosphate in the regulation of acid secretion in the isolated stomach of guinea-pig. 1 The rate of acid secretion and mucosal cyclic adenosine 3',5'-monophosphate (cyclic AMP) content have been measured on the same guinea-pig isolated stomach preparation in response to histamine, theophylline and ICI 63197, a potent phosphodiesterase inhibitor. 2 Unstimulated control tissues had a spontaneous rate of acid secretion of 74.41 +/- 9.06 mumol H+/g wet wt. of mucosa per hour (s.e. mean, n = 20) and a cyclic AMP content of 0.517 +/- 0.058 mnol/g wet weight. 3 Each of the three drugs caused an increase in both the mucosal cyclic AMP content and the rate of acid secretion. These increases were inearly related to the logarithm of drug concentration for each drug. 4 There were no statistically significant differences between the three regression coefficients obtained for acid on drug and for cyclic AMP on drug. 5 There was a significant correlation between the rate of acid secretion and mucosal cyclic AMP content in stimulated preparations (P less than 0.001) and also in control preparations which received no drug (P less than 0.05). 6 These results are discussed in relation to the possible role of cyclic AMP in the mediation of acid secretory responses in the mammalian stomach."}
{"id": "PMID:189874", "title": "Influence of neuroglial transport on the action of gamma-aminobutyric acid on mammalian ganglion cells.", "content": "1 The effect of inhibiting the transport of gamma-aminobutyric acid (GABA) by neuroglial cells on the depolarizing action of exogenous amino acids on isolated superior cervical ganglia of the rat was studied. 1 Transport (measured by uptake of [3H]-GABA) was inhibited by (a) reducing external [na+] from 143 to 2mM and (b) administering alternative carrier-sbustrates, 3-amino-n-butyric acid (beta-amino-butyric acid, BABA) and (+/-)-nipecotic acid at a concentration of 1 mM. 3 All three procedures enhanced the depolarization produced by low concentrations of GABA (less than or equal to 10 muM) but did not alter the maximum response, nor the response to 3-aminopropanesulphonic acid (a gabamimetic with low affinity for the neuroglial carrier). 4 It is concluded that the neuroglial uptake process can limit the action of exogenous GABA upon neurones, by reducing the interstitial GABA concentration.", "contents": "Influence of neuroglial transport on the action of gamma-aminobutyric acid on mammalian ganglion cells. 1 The effect of inhibiting the transport of gamma-aminobutyric acid (GABA) by neuroglial cells on the depolarizing action of exogenous amino acids on isolated superior cervical ganglia of the rat was studied. 1 Transport (measured by uptake of [3H]-GABA) was inhibited by (a) reducing external [na+] from 143 to 2mM and (b) administering alternative carrier-sbustrates, 3-amino-n-butyric acid (beta-amino-butyric acid, BABA) and (+/-)-nipecotic acid at a concentration of 1 mM. 3 All three procedures enhanced the depolarization produced by low concentrations of GABA (less than or equal to 10 muM) but did not alter the maximum response, nor the response to 3-aminopropanesulphonic acid (a gabamimetic with low affinity for the neuroglial carrier). 4 It is concluded that the neuroglial uptake process can limit the action of exogenous GABA upon neurones, by reducing the interstitial GABA concentration."}
{"id": "PMID:189877", "title": "Distribution of angiotensin II receptors in rat brain.", "content": "Angiotensin II binding activity of rat brain particles was examined using [125I]-angiotensin II (0.1-0.3 nM) in the presence and absence of excess unlabelled angiotensin II. Certain features of the binding suggested that physiological receptors were involved. The binding activity was temperature dependent and was increased 3-fold by the addition of 0.5 M EDTA. The binding appeared specific as judged by inhibition with angiotensin II agonists and antagonists. The \"specific\" binding was saturable, two-thirds reversible and occurred with high affinity. The equilibrium dissociation constant (Kd) of the \"specific\" binding was 0.9 nM. Subcellular fractionation studies indicated that over 90% of the binding was associated with particulate matter and was concentrated in the crude microsomal fraction. Binding was localized to the midbrain, thalamus, septum, hypothalamus and medulla; Very low levels of binding were found in the cortex, hippocampus and striatum; The lateral septum had the highest binding activity of all the tissues examined. Subdivision of the medulla showed that the highest binding activity was associated with the area postrema and medullary regions ventral to this organ.", "contents": "Distribution of angiotensin II receptors in rat brain. Angiotensin II binding activity of rat brain particles was examined using [125I]-angiotensin II (0.1-0.3 nM) in the presence and absence of excess unlabelled angiotensin II. Certain features of the binding suggested that physiological receptors were involved. The binding activity was temperature dependent and was increased 3-fold by the addition of 0.5 M EDTA. The binding appeared specific as judged by inhibition with angiotensin II agonists and antagonists. The \"specific\" binding was saturable, two-thirds reversible and occurred with high affinity. The equilibrium dissociation constant (Kd) of the \"specific\" binding was 0.9 nM. Subcellular fractionation studies indicated that over 90% of the binding was associated with particulate matter and was concentrated in the crude microsomal fraction. Binding was localized to the midbrain, thalamus, septum, hypothalamus and medulla; Very low levels of binding were found in the cortex, hippocampus and striatum; The lateral septum had the highest binding activity of all the tissues examined. Subdivision of the medulla showed that the highest binding activity was associated with the area postrema and medullary regions ventral to this organ."}
{"id": "PMID:189881", "title": "Fractionation of human low density lipoprotein by column chromatography.", "content": "We have devised a method to fractionate low density lipoprotein (LDL) into subspecies by means of column chromatography. DEAE-agarose columns, 2.6 X 60 cm, were loaded with LDL (25-45 mg LDL protein) and eluted with a 0.045-0.13 M NaCl gradient. The LDL eluted over a volume of 900 ml. Specific portions of the eluted LDL, reapplied to a column identical with the original, reelute at about the same point. Altering the NaCl concentration of the elution fluid changed the elution volume. The cholesterol-protein ratio of the LDL subfractions was progressively lower in fractions eluting at higher NaCl concentrations. These results indicate the LDL is not a homogenous lipoprotein species but consists of subfractions which differ in at least charge and cholesterol content.", "contents": "Fractionation of human low density lipoprotein by column chromatography. We have devised a method to fractionate low density lipoprotein (LDL) into subspecies by means of column chromatography. DEAE-agarose columns, 2.6 X 60 cm, were loaded with LDL (25-45 mg LDL protein) and eluted with a 0.045-0.13 M NaCl gradient. The LDL eluted over a volume of 900 ml. Specific portions of the eluted LDL, reapplied to a column identical with the original, reelute at about the same point. Altering the NaCl concentration of the elution fluid changed the elution volume. The cholesterol-protein ratio of the LDL subfractions was progressively lower in fractions eluting at higher NaCl concentrations. These results indicate the LDL is not a homogenous lipoprotein species but consists of subfractions which differ in at least charge and cholesterol content."}
{"id": "PMID:189882", "title": "In vitro effect of free bile acids on the bile canalicular membrane phospholipids in the rat.", "content": "Liver cell plasma membranes of male rats were isolated and separated into two fractions, one rich in bile canalicular membranes (BCM) and the other comprising the rest of the plasma membrane (PM). Aliquots of BCM, PM, and microsomes were incubated with deoxycholic, chenodeoxycholic, or cholic acid at bile acid - membrane phospholipid mole ratios up to 100, and the phospholipid solubilization from the PM and from microsomes was linear and apparently nonselective, while that from BCM was biphasic and distinctly selective. Phosphatidyl choline and phosphatidyl ethanolamine made up 90% of the phospholipids solubilized from the BCM at a bile acid - membrane phospholipid mole ratio sufficient to solubilize about 50% of the total phospholipids of the BCM. Of particular interest was the observation that the molecular species and fatty acid composition of the phospholipids solubilized from the BCM under these experimental conditions were similar to those of bile obtained from the same animal, and were quite unlike those solubilized at higher bile acid - phospholipids mole ratios. The data are discussed in terms of the mechanism of the biliary secretion of phospholipids.", "contents": "In vitro effect of free bile acids on the bile canalicular membrane phospholipids in the rat. Liver cell plasma membranes of male rats were isolated and separated into two fractions, one rich in bile canalicular membranes (BCM) and the other comprising the rest of the plasma membrane (PM). Aliquots of BCM, PM, and microsomes were incubated with deoxycholic, chenodeoxycholic, or cholic acid at bile acid - membrane phospholipid mole ratios up to 100, and the phospholipid solubilization from the PM and from microsomes was linear and apparently nonselective, while that from BCM was biphasic and distinctly selective. Phosphatidyl choline and phosphatidyl ethanolamine made up 90% of the phospholipids solubilized from the BCM at a bile acid - membrane phospholipid mole ratio sufficient to solubilize about 50% of the total phospholipids of the BCM. Of particular interest was the observation that the molecular species and fatty acid composition of the phospholipids solubilized from the BCM under these experimental conditions were similar to those of bile obtained from the same animal, and were quite unlike those solubilized at higher bile acid - phospholipids mole ratios. The data are discussed in terms of the mechanism of the biliary secretion of phospholipids."}
{"id": "PMID:189883", "title": "The effect of diabetes and insulin on adipose lactate dehydrogenase isozymes.", "content": "Adipose lactate dehydrogenase (LDH) (EC 1.1.1.27) isozyme distribution was altered in streptozotocin-diabetic and fasting rats resulting from a relative reduction of subunit A. Treatment with insulin for 2 days partially restored the relative content of isozyme 5 to control values in the diabetic rats, and the effect of insulin was not inhibited by simultaneous injection of actinomycin D or puromycin. When the epididymal adipose tissues isolated from control animals were incubated in vitro with dibutyryl adenosine 3',5'-cyclic monophosphate or epinephrine, a relative decrease in subunit A was observed; whereas, either compound caused an increase in subunit A in diabetic tissues. The findings suggest that the redistribution of LDH isozyme under these conditions is to prevent excessive accumulation of lactate in the tissue.", "contents": "The effect of diabetes and insulin on adipose lactate dehydrogenase isozymes. Adipose lactate dehydrogenase (LDH) (EC 1.1.1.27) isozyme distribution was altered in streptozotocin-diabetic and fasting rats resulting from a relative reduction of subunit A. Treatment with insulin for 2 days partially restored the relative content of isozyme 5 to control values in the diabetic rats, and the effect of insulin was not inhibited by simultaneous injection of actinomycin D or puromycin. When the epididymal adipose tissues isolated from control animals were incubated in vitro with dibutyryl adenosine 3',5'-cyclic monophosphate or epinephrine, a relative decrease in subunit A was observed; whereas, either compound caused an increase in subunit A in diabetic tissues. The findings suggest that the redistribution of LDH isozyme under these conditions is to prevent excessive accumulation of lactate in the tissue."}
{"id": "PMID:189884", "title": "Glycosylation of apoproteins of rat very low density lipoproteins during transit through the hepatic Golgi apparatus.", "content": "The glycosylation of apo very low density lipoproteins (apo-VLDL) in vivo was studied by following the incorporation of [14C]glucosamine into several groups of apoproteins of VLDL isolated from hepatic Golgi fractions and from serum of sucrose-fed, colchicine-treated rats. Simultaneous incorporation of [3H]leucine was used to quantitate the apoproteins following separation by polyacrylamide gel electrophoresis. Experimental conditions were selected so that the 14C:3H ratio in the apoproteins permitted estimations of the extent of glycosylation by glucosamine and its metabolites. A rapidly decreasing 14C:3H ratio was noted in serum apo-VLDL for the first 30 min after administration of the isotopically labelled precursors, followed by stabilization of the ratio. These data are consistent with the glycosylation of a preformed pool of apo-VLDL, probably apo-B. Glucosamine was progressively incorporated into apo-VLDL during transition from the forming face of the Golgi apparatus to the secretory vesicles, as indicated by an increasing 14C:3H ratio. On the other hand, the ratio of the rapidly migrating apoproteins of VLDL, corresponding to the apo-C-II and apo-C-III, showed the opposite trend, as did total apo high density lipoprotein (apo-HDL) and the rapidly migrating bands of apo-HDL. Division of the rapidly migrating apoproteins of VLDL into upper bands (probably apo-C-II and apo-C-III-0) and lower bands (probably apo-C-III-3) resulted in a 14C:3H ratio near zero in the upper band apoproteins, consistent with the absence of carbohydrates. The lower band showed a rising 14C:3H ratio during transition through the Golgi apparatus, suggesting increased glycosylation, The decreasing 14C:3H ratio in the rapidly migrating proteins is therefore due to the acquisition of apo-C-II and apo-C-III-0 by VLDL during passage from the forming face to the secretory vesicles of the Golgi apparatus.", "contents": "Glycosylation of apoproteins of rat very low density lipoproteins during transit through the hepatic Golgi apparatus. The glycosylation of apo very low density lipoproteins (apo-VLDL) in vivo was studied by following the incorporation of [14C]glucosamine into several groups of apoproteins of VLDL isolated from hepatic Golgi fractions and from serum of sucrose-fed, colchicine-treated rats. Simultaneous incorporation of [3H]leucine was used to quantitate the apoproteins following separation by polyacrylamide gel electrophoresis. Experimental conditions were selected so that the 14C:3H ratio in the apoproteins permitted estimations of the extent of glycosylation by glucosamine and its metabolites. A rapidly decreasing 14C:3H ratio was noted in serum apo-VLDL for the first 30 min after administration of the isotopically labelled precursors, followed by stabilization of the ratio. These data are consistent with the glycosylation of a preformed pool of apo-VLDL, probably apo-B. Glucosamine was progressively incorporated into apo-VLDL during transition from the forming face of the Golgi apparatus to the secretory vesicles, as indicated by an increasing 14C:3H ratio. On the other hand, the ratio of the rapidly migrating apoproteins of VLDL, corresponding to the apo-C-II and apo-C-III, showed the opposite trend, as did total apo high density lipoprotein (apo-HDL) and the rapidly migrating bands of apo-HDL. Division of the rapidly migrating apoproteins of VLDL into upper bands (probably apo-C-II and apo-C-III-0) and lower bands (probably apo-C-III-3) resulted in a 14C:3H ratio near zero in the upper band apoproteins, consistent with the absence of carbohydrates. The lower band showed a rising 14C:3H ratio during transition through the Golgi apparatus, suggesting increased glycosylation, The decreasing 14C:3H ratio in the rapidly migrating proteins is therefore due to the acquisition of apo-C-II and apo-C-III-0 by VLDL during passage from the forming face to the secretory vesicles of the Golgi apparatus."}
{"id": "PMID:189885", "title": "The role of metabolic energy in the lethal action of basic proteins on Candida albicans.", "content": "Comparative studies were made on the destructive effects of certain basic proteins on a strain of Candida albicans and two of its respiration-impaired mutants. Both by direct plate counts of survivors and by quantitative ultraviolet spectrophotometric analyses of released cellular constituents, the respiration-impaired mutants were less vulnerable to the destructive actions of the basic proteins than were ordinary wild-type cells. The lethal incidence and the ultraviolet absorbing cellular substances released from wild-type cells by the proteins were markedly decreased in the presence of the oxidative phosphorylation uncouplers sodium azide, 2,4-dinitrophenol, and salicylanide and approximately equal to the effects produced on an oxidative phosphorylation mutant not treated with the uncouplers. The heightened resistance of a culture through mutational or chemical impairment of its respiratory system suggests a role of metabolic energy in the destructive action of various basic proteins on yeast cells.", "contents": "The role of metabolic energy in the lethal action of basic proteins on Candida albicans. Comparative studies were made on the destructive effects of certain basic proteins on a strain of Candida albicans and two of its respiration-impaired mutants. Both by direct plate counts of survivors and by quantitative ultraviolet spectrophotometric analyses of released cellular constituents, the respiration-impaired mutants were less vulnerable to the destructive actions of the basic proteins than were ordinary wild-type cells. The lethal incidence and the ultraviolet absorbing cellular substances released from wild-type cells by the proteins were markedly decreased in the presence of the oxidative phosphorylation uncouplers sodium azide, 2,4-dinitrophenol, and salicylanide and approximately equal to the effects produced on an oxidative phosphorylation mutant not treated with the uncouplers. The heightened resistance of a culture through mutational or chemical impairment of its respiratory system suggests a role of metabolic energy in the destructive action of various basic proteins on yeast cells."}
{"id": "PMID:189886", "title": "Pigment variant of neuronal ceroid-lipofuscinosis (Kufs' disease).", "content": "A case of pigment variant of Kufs' disease is presented. The nature of the extra-neuronal pigment is discussed. Despite some of the histochemical discrepancies that existed between this pigment and the material that had accumulated in the nerve cells, they seemed to be ultrastructurally related. The hepatocytes contained numerous heterogeneous cytosomes, some of which resembled the storage material of Niemann-Pick's disease. Clinically the syndrome may present with progressive ataxia, spontaneous and reflex, coarse myoclonic jerks and eventual mental deterioration as well as epilepsy and muscle wasting. The pigment variant cannot be distinguished from Kufs' disease except pathologically.", "contents": "Pigment variant of neuronal ceroid-lipofuscinosis (Kufs' disease). A case of pigment variant of Kufs' disease is presented. The nature of the extra-neuronal pigment is discussed. Despite some of the histochemical discrepancies that existed between this pigment and the material that had accumulated in the nerve cells, they seemed to be ultrastructurally related. The hepatocytes contained numerous heterogeneous cytosomes, some of which resembled the storage material of Niemann-Pick's disease. Clinically the syndrome may present with progressive ataxia, spontaneous and reflex, coarse myoclonic jerks and eventual mental deterioration as well as epilepsy and muscle wasting. The pigment variant cannot be distinguished from Kufs' disease except pathologically."}
{"id": "PMID:189887", "title": "Technetium pyrophosphate scanning in the detection of acute myocardial infarction: clinical experience.", "content": "Technetium-99m-stannous pyrophosphate (99mTc-PYP) accumulates in acutely infarcted myocardium and can be detected by scintiscanning. The clinical value of 99mTc-PYP scintiscanning was studied in 83 patients 6 hours to 21 days after the onset of acute chest pain. In 12 patients with normal electrocardiograms and serum enzyme values no uptake of 99mTc-PYP was detected on the scintigrams. Of 44 patients with electrocardiographic or enzyme evidence, or both, of acute myocardial infarction the scintigrams were positive in 31, \"questionable\" in 2 and negative in 11; no positive scan was obtained within 12 hours of the onset of pain, and the scans generally remained positive for up to 5 days. In 24 patients with evidence of prolonged myocardial ischemia the scans were positive in 2, questionable in 4 and negative in 18. The scans were negative in each of three patients with acute or constrictive pericarditis. Localization by electrocardiography and scintiscanning correlated nearly perfectly for transmural infarcts but subendocardial infarcts could not always be localized precisely by scintiscanning. The infarct area (total area of 99mTc-PYP uptake) correlated well with the peak serum value of creatine phosphokinase.", "contents": "Technetium pyrophosphate scanning in the detection of acute myocardial infarction: clinical experience. Technetium-99m-stannous pyrophosphate (99mTc-PYP) accumulates in acutely infarcted myocardium and can be detected by scintiscanning. The clinical value of 99mTc-PYP scintiscanning was studied in 83 patients 6 hours to 21 days after the onset of acute chest pain. In 12 patients with normal electrocardiograms and serum enzyme values no uptake of 99mTc-PYP was detected on the scintigrams. Of 44 patients with electrocardiographic or enzyme evidence, or both, of acute myocardial infarction the scintigrams were positive in 31, \"questionable\" in 2 and negative in 11; no positive scan was obtained within 12 hours of the onset of pain, and the scans generally remained positive for up to 5 days. In 24 patients with evidence of prolonged myocardial ischemia the scans were positive in 2, questionable in 4 and negative in 18. The scans were negative in each of three patients with acute or constrictive pericarditis. Localization by electrocardiography and scintiscanning correlated nearly perfectly for transmural infarcts but subendocardial infarcts could not always be localized precisely by scintiscanning. The infarct area (total area of 99mTc-PYP uptake) correlated well with the peak serum value of creatine phosphokinase."}
{"id": "PMID:189888", "title": "Home peritoneal dialysis: 3 years' experience in Toronto.", "content": "From November 1972 to November 1975, 52 males and 39 females aged 11 to 71 years were trained for home peritoneal dialysis. Dialysis was performed through a permanent catheter 4 nights a week. The first 11 patients used the manual system, exchanging 2 / of dialysate solution every 50 to 60 minutes. Subsequently 73 patients used the automatic cycler and commercially available dialysate and 7 patients used Tenckhoff's reverse osmosis peritoneal dialysis machine. The average duration of training was 15, 11.6 and 15 dialysis days, respectively, for the three methods. For the 83 patients followed up, the average duration of home dialysis was 8.3 months (range, 0.5 to 33 months); the total number of dialyses at home was 10 571. Ten received a transplant, 20 were transferred to hospital peritoneal dialysis or hemodialysis, 8 died and 48 continued with home dialysis. Twenty-three patients had a total of 33 episodes of peritonitis, an incidence of 27.7% among the patients in the program for up to 3 years or 0.3% among all the dialyses. By November 1975, 46 patients had returned to their predialysis lifestyle, 18 were working part-time, 10 were able to work but were not doing  so, and 9 were unable to work or care for themselves.", "contents": "Home peritoneal dialysis: 3 years' experience in Toronto. From November 1972 to November 1975, 52 males and 39 females aged 11 to 71 years were trained for home peritoneal dialysis. Dialysis was performed through a permanent catheter 4 nights a week. The first 11 patients used the manual system, exchanging 2 / of dialysate solution every 50 to 60 minutes. Subsequently 73 patients used the automatic cycler and commercially available dialysate and 7 patients used Tenckhoff's reverse osmosis peritoneal dialysis machine. The average duration of training was 15, 11.6 and 15 dialysis days, respectively, for the three methods. For the 83 patients followed up, the average duration of home dialysis was 8.3 months (range, 0.5 to 33 months); the total number of dialyses at home was 10 571. Ten received a transplant, 20 were transferred to hospital peritoneal dialysis or hemodialysis, 8 died and 48 continued with home dialysis. Twenty-three patients had a total of 33 episodes of peritonitis, an incidence of 27.7% among the patients in the program for up to 3 years or 0.3% among all the dialyses. By November 1975, 46 patients had returned to their predialysis lifestyle, 18 were working part-time, 10 were able to work but were not doing  so, and 9 were unable to work or care for themselves."}
{"id": "PMID:189889", "title": "Adenovirus type 3 pneumonia causing lung damage in childhood.", "content": "An outbreak of adenovirus type 3 infection occurred in a hospital in 19 North American Indian infants and young children who were being treated for unrelated problems. Pneumonia occurred in 14 and was usually severe, with persistent signs of airway obstruction. Eleven of the 14 were followed periodically and complete medical reviews were conducted 8 to 10 years later. Ten had abnormal chest radiographs, and bronchography revealed bronchiectasis and minor airways changes in seven. In three cases there was clear evidence that these changes were directly related to the adenovirus type 3 infection. Pulmonary function studies showed a combination of restrictive and obstructive changes with minimal hypoxemia in most. Despite the presence of a persistent productive cough all were able to carry on a relatively normal life.", "contents": "Adenovirus type 3 pneumonia causing lung damage in childhood. An outbreak of adenovirus type 3 infection occurred in a hospital in 19 North American Indian infants and young children who were being treated for unrelated problems. Pneumonia occurred in 14 and was usually severe, with persistent signs of airway obstruction. Eleven of the 14 were followed periodically and complete medical reviews were conducted 8 to 10 years later. Ten had abnormal chest radiographs, and bronchography revealed bronchiectasis and minor airways changes in seven. In three cases there was clear evidence that these changes were directly related to the adenovirus type 3 infection. Pulmonary function studies showed a combination of restrictive and obstructive changes with minimal hypoxemia in most. Despite the presence of a persistent productive cough all were able to carry on a relatively normal life."}
{"id": "PMID:189890", "title": "Malignant mixed tumor of salivary origin: a clinicopathologic study of 146 cases.", "content": "A 30-year Memorial Hospital experience with 146 patients with malignant mixed tumor is reviewed. These comprised 5% of 2,743 patients who were treated for salivary neoplasms from 1939 through 1968. The tumors arose in the parotid gland in 108 patients, submaxillary gland in 23 patients, mucus or so-called minor salivary glands in 16 patients, and sublingual gland in one. In terms of our total experience, 11% of all submaxillary tumors proved to be of the malignant mixed variety as compared to 6% of parotid tumors and 3% of minor salivary tumors, respectively. Seventy-one patients (48%) had previously received therapy elsewhere. Results of treatment are presented and the factors which influenced the results are discussed.", "contents": "Malignant mixed tumor of salivary origin: a clinicopathologic study of 146 cases. A 30-year Memorial Hospital experience with 146 patients with malignant mixed tumor is reviewed. These comprised 5% of 2,743 patients who were treated for salivary neoplasms from 1939 through 1968. The tumors arose in the parotid gland in 108 patients, submaxillary gland in 23 patients, mucus or so-called minor salivary glands in 16 patients, and sublingual gland in one. In terms of our total experience, 11% of all submaxillary tumors proved to be of the malignant mixed variety as compared to 6% of parotid tumors and 3% of minor salivary tumors, respectively. Seventy-one patients (48%) had previously received therapy elsewhere. Results of treatment are presented and the factors which influenced the results are discussed."}
{"id": "PMID:189891", "title": "RNA viruses and cancer: Lucy Wortham James Lecture (Basic Science).", "content": "Some animal viruses that contain RNA replicate through a DNA intermediate. The molecular details of the replication of these viruses, which are called ribodenoxyviruses, are starting to be known. The ribodenoxyviruses belonging to a single species may either cause sarcomas, leukemia or no disease. The viruses belonging to a single species differ only in whether or not they contain genes for disease formation. In the case of Rous sarcoma virus, the virus causes sarcomas by adding a gene for sarcoma formation to the genome of infected cells. Ribodeoxyviruses appear to undergo different kinds of genetic changes at extraordinarily high rates. In addition, nucleotide sequences related to ribodeoxyvirus RNA are present in the DNA of many uninfected cells. These nucleotide sequences may represent a virus precursor, and ribodeoxyviruses are hypothesized to have evolved from these nucleotide sequences in uninfected cells. These data have led us to hypothesis that non-viral carcinogens act to mutate a cellular gene(s) that is involved in the same types of information transfer and genetic variation as ribodeoxyviruses and thus give rise to the formation of cancer gene(s).", "contents": "RNA viruses and cancer: Lucy Wortham James Lecture (Basic Science). Some animal viruses that contain RNA replicate through a DNA intermediate. The molecular details of the replication of these viruses, which are called ribodenoxyviruses, are starting to be known. The ribodenoxyviruses belonging to a single species may either cause sarcomas, leukemia or no disease. The viruses belonging to a single species differ only in whether or not they contain genes for disease formation. In the case of Rous sarcoma virus, the virus causes sarcomas by adding a gene for sarcoma formation to the genome of infected cells. Ribodeoxyviruses appear to undergo different kinds of genetic changes at extraordinarily high rates. In addition, nucleotide sequences related to ribodeoxyvirus RNA are present in the DNA of many uninfected cells. These nucleotide sequences may represent a virus precursor, and ribodeoxyviruses are hypothesized to have evolved from these nucleotide sequences in uninfected cells. These data have led us to hypothesis that non-viral carcinogens act to mutate a cellular gene(s) that is involved in the same types of information transfer and genetic variation as ribodeoxyviruses and thus give rise to the formation of cancer gene(s)."}
{"id": "PMID:189892", "title": "A comparative study of some pathologic features of mammary carcinoma in Tokyo, Japan and New York, USA.", "content": "Epidemiologic and clinical studies conducted in the past 15 years have demonstrated striking differences in the biology of mammary carcinoma among Japanese and American women living in their native countries. These variations have, in part, been related to some differences in the characteristics of the primary tumors between the two groups. As part of a collaborative study we have had an opportunity to compare the stage of disease and to examine and compare histological sections of patients with breast carcinoma treated in 1973-74 at the National Cancer Center Hospital (NCH) in Tokyo and in 1974 at the Memorial Hospital (MH) in New York. The former group consisted of 216 and the latter of 555 carcinomas. Fewer patients in each group had axillary metastases than reported in a prior study of patients treated at MSKCC and in Tokyo 20 to 30 years earlier. Negative axillary nodes were now found in 58% of the MH patients and in 63% of women treated at the NCH. The magnitude of improvement in stage relative to the prior report was similar in both groups. However, it would appear that the change occurred mainly from the mid-1950s to the 1960s in New York and approximately 10 years later in Tokyo. Results of this study confirming prior reports were: (1) higher frequency of colloid and of medullary carcinoma with lymphoid stroma and lesser frequency of lobular carcinoma in the Japanese patients; (2) more intense lymphoid infiltrate in and around primary tumors in Japanese women; (3) higher frequency of rounded or circumscribed tumors in Japanese women; and (4) the more frequent occurrence of intralymphatic tumor emboli within the breast in American women. The difference in the frequency of lobular carcinoma was less striking when comparison was limited to patients with unilateral carcinoma.", "contents": "A comparative study of some pathologic features of mammary carcinoma in Tokyo, Japan and New York, USA. Epidemiologic and clinical studies conducted in the past 15 years have demonstrated striking differences in the biology of mammary carcinoma among Japanese and American women living in their native countries. These variations have, in part, been related to some differences in the characteristics of the primary tumors between the two groups. As part of a collaborative study we have had an opportunity to compare the stage of disease and to examine and compare histological sections of patients with breast carcinoma treated in 1973-74 at the National Cancer Center Hospital (NCH) in Tokyo and in 1974 at the Memorial Hospital (MH) in New York. The former group consisted of 216 and the latter of 555 carcinomas. Fewer patients in each group had axillary metastases than reported in a prior study of patients treated at MSKCC and in Tokyo 20 to 30 years earlier. Negative axillary nodes were now found in 58% of the MH patients and in 63% of women treated at the NCH. The magnitude of improvement in stage relative to the prior report was similar in both groups. However, it would appear that the change occurred mainly from the mid-1950s to the 1960s in New York and approximately 10 years later in Tokyo. Results of this study confirming prior reports were: (1) higher frequency of colloid and of medullary carcinoma with lymphoid stroma and lesser frequency of lobular carcinoma in the Japanese patients; (2) more intense lymphoid infiltrate in and around primary tumors in Japanese women; (3) higher frequency of rounded or circumscribed tumors in Japanese women; and (4) the more frequent occurrence of intralymphatic tumor emboli within the breast in American women. The difference in the frequency of lobular carcinoma was less striking when comparison was limited to patients with unilateral carcinoma."}
{"id": "PMID:189893", "title": "Prospective study of non-infiltrating carcinoma of the breast.", "content": "A long-term prospective study of non-infiltrating breast carcinoma is being carried out in order to study the natural history and proper management of such lesions with particular interest in patients treated solely by local excision. During an 11-year period, 175 patients with lobular Ca in situ and intraductal Ca have been followed. None has developed recurrent disease including 18 undergoing wide local excision only. Histologic examination revealed that 36% of mastectomy specimens showed multifocal lesions, whereas only one of the patients treated by wide local excision had more than one microscopic focus. For these reasons total mastectomy is recommended as the treatment of non-infiltrating breast carcinoma. Subsequent development of contralateral cancer has occurred in ten patients.", "contents": "Prospective study of non-infiltrating carcinoma of the breast. A long-term prospective study of non-infiltrating breast carcinoma is being carried out in order to study the natural history and proper management of such lesions with particular interest in patients treated solely by local excision. During an 11-year period, 175 patients with lobular Ca in situ and intraductal Ca have been followed. None has developed recurrent disease including 18 undergoing wide local excision only. Histologic examination revealed that 36% of mastectomy specimens showed multifocal lesions, whereas only one of the patients treated by wide local excision had more than one microscopic focus. For these reasons total mastectomy is recommended as the treatment of non-infiltrating breast carcinoma. Subsequent development of contralateral cancer has occurred in ten patients."}
{"id": "PMID:189894", "title": "Immunocompetence of cancer patients treated with Levamisole.", "content": "Nineteen outpatients with malignant melanoma and squamous cell carcinoma of the head and neck, who had surgical resection for complete removal of the tumor and no demonstrable metastases following surgery, were administered Levamisole (p.o., 150 mg per day, two days per week) and maintained on this dose for at least six months. Of this group, drug therapy was discontinued in four patients because of severe \"flu-like\" syndromes leaving a group of 15 patients for detailed analysis. T-lymphocyte percentages and levels, cAMP levels in the lymphocytes and a battery of skin tests for recall antigens were evaluated following surgery and at various intervals during immunotherapy. Patients who responded well to the treatment showed increased levels of T-lymphocytes and increased cAMP levels, whereas non-responders had low T-cell levels and low cAMP levels. Also positive skin test reactions were observed in most patients who responded well to immunotherapy, although this was the least reliable indicator of patient response. Eight of the nine patients in the melanoma group have responded well clinically, whereas five of the six squamous cell carcinoma patients have developed recurrences.", "contents": "Immunocompetence of cancer patients treated with Levamisole. Nineteen outpatients with malignant melanoma and squamous cell carcinoma of the head and neck, who had surgical resection for complete removal of the tumor and no demonstrable metastases following surgery, were administered Levamisole (p.o., 150 mg per day, two days per week) and maintained on this dose for at least six months. Of this group, drug therapy was discontinued in four patients because of severe \"flu-like\" syndromes leaving a group of 15 patients for detailed analysis. T-lymphocyte percentages and levels, cAMP levels in the lymphocytes and a battery of skin tests for recall antigens were evaluated following surgery and at various intervals during immunotherapy. Patients who responded well to the treatment showed increased levels of T-lymphocytes and increased cAMP levels, whereas non-responders had low T-cell levels and low cAMP levels. Also positive skin test reactions were observed in most patients who responded well to immunotherapy, although this was the least reliable indicator of patient response. Eight of the nine patients in the melanoma group have responded well clinically, whereas five of the six squamous cell carcinoma patients have developed recurrences."}
{"id": "PMID:189895", "title": "A new approach in specific, active immunotherapy.", "content": "A vaccinia virus-lysed autochthonous tumor cell vaccine (vaccinia oncolysate) is introduced as a new specific, active immunotherapeutic agent against human cancer. Mouse experiments showed the vaccine to be a safe and potent immune mechanism stimulator. Human experimentation was undertaken in the knowledge of relative safety of the components of the vaccine, i.e. vaccinia vaccine and lysed, autochthonous tumor cells. Vaccine-treated patients had advanced metastatic cancer but reacted to one or more common recall antigen skin tests. None of the 13 patients had untoward responses; 7/13 patients had classic delayed hypersensitivity reactions at the vaccine injection sites; and 2/7 patients with injection site reactions had significant reduction in tumor burden. These results indicate that this vaccine is a specific, active immune mechanism stimulator, and may prove to be a useful therapeutic agent in the treatment of human cancer.", "contents": "A new approach in specific, active immunotherapy. A vaccinia virus-lysed autochthonous tumor cell vaccine (vaccinia oncolysate) is introduced as a new specific, active immunotherapeutic agent against human cancer. Mouse experiments showed the vaccine to be a safe and potent immune mechanism stimulator. Human experimentation was undertaken in the knowledge of relative safety of the components of the vaccine, i.e. vaccinia vaccine and lysed, autochthonous tumor cells. Vaccine-treated patients had advanced metastatic cancer but reacted to one or more common recall antigen skin tests. None of the 13 patients had untoward responses; 7/13 patients had classic delayed hypersensitivity reactions at the vaccine injection sites; and 2/7 patients with injection site reactions had significant reduction in tumor burden. These results indicate that this vaccine is a specific, active immune mechanism stimulator, and may prove to be a useful therapeutic agent in the treatment of human cancer."}
{"id": "PMID:189896", "title": "The tumor specific immune response of experimental active-specific immunotherapy.", "content": "Evidence for augmentation of antigenic recognition was investigated by measuring antigen-specific lymphocyte stimulation in animals which were minimally immunized with Con A-modified tumor cells. Comparison of lymphocyte stimulation response was made to animals immunized with unmodified tumor cells or sham immunization. Markedly heightened, tritiated Thymidine incorporation was observed in the lymph node cells from animals immunized with Concanavalin A-modified tumor cells, while minimal response was observed in control hosts. These preliminary findings imply that Con A-modified tumor cell immunotherapy may work by augmenting the host's capacity to recognized minimal differences in immunogenicity between tumor cells and the normal cells or origin. This modulation of the immune response may be a key factor in the success of active-specific immunotherapy.", "contents": "The tumor specific immune response of experimental active-specific immunotherapy. Evidence for augmentation of antigenic recognition was investigated by measuring antigen-specific lymphocyte stimulation in animals which were minimally immunized with Con A-modified tumor cells. Comparison of lymphocyte stimulation response was made to animals immunized with unmodified tumor cells or sham immunization. Markedly heightened, tritiated Thymidine incorporation was observed in the lymph node cells from animals immunized with Concanavalin A-modified tumor cells, while minimal response was observed in control hosts. These preliminary findings imply that Con A-modified tumor cell immunotherapy may work by augmenting the host's capacity to recognized minimal differences in immunogenicity between tumor cells and the normal cells or origin. This modulation of the immune response may be a key factor in the success of active-specific immunotherapy."}
{"id": "PMID:189897", "title": "The increasing importance of radiation therapy in the improved prognosis of children with Wilms' tumor.", "content": "Treatment results for 32 children with Wilms' tumor seen at the JCRT, CHMC and SFCI from January 1, 1971, through December 31, 1975, are presented. Indications for and technical details of irridation are discussed. The uniform efficacy of irradiation in preventing local relapse in all patients presenting with unilateral disease despite tumor spill in nine is stressed. Actuarial survival of nearly 80% of all patients seen and followed for more than 2 years has been achieved. Eight of 14 patients with documented pulmonary relapse have been controlled with irradiation, chemotherapy and surgery. The importance of an aggressive multidisciplinary approach to this tumor is stressed.", "contents": "The increasing importance of radiation therapy in the improved prognosis of children with Wilms' tumor. Treatment results for 32 children with Wilms' tumor seen at the JCRT, CHMC and SFCI from January 1, 1971, through December 31, 1975, are presented. Indications for and technical details of irridation are discussed. The uniform efficacy of irradiation in preventing local relapse in all patients presenting with unilateral disease despite tumor spill in nine is stressed. Actuarial survival of nearly 80% of all patients seen and followed for more than 2 years has been achieved. Eight of 14 patients with documented pulmonary relapse have been controlled with irradiation, chemotherapy and surgery. The importance of an aggressive multidisciplinary approach to this tumor is stressed."}
{"id": "PMID:189898", "title": "Radiation therapy in the management of carcinoma of the lung.", "content": "Carcinoma of the lung is the most common cancer in men in the United States and a major cause of death. This is due to the inadequate techniques for screening of high-risk patients and for detection of the tumor in early stages, before distant dissemination occurs. Although some progress has been made in the past, particularly in improving the knowledge of natural history and pathological characteristics of the disease, and there are better indications for surgical treatment and irradiation and the effective use of cytotoxic agents in selected groups of patients, particularly those with small cell undifferentiated carcinoma, the mortality rate is still very high. A great deal of investigation remains to be done in carcinoma of the lung concerning the basic cell kinetics of the tumor and the optimal conditions for the use of surgery, irradiation, chemotherapy or combinations of these agents in the treatment of these patients before survival rates can be substantially improved. Since the most important factor in patient mortality is distant tumor dissemination, it must be stressed that parameters other than survival should be used to evaluate the effectiveness of irradiation, surgery or combinations in the control of local and regional bronchogenic carcinoma. These efforts should be intensified through properly designed clinical trials.", "contents": "Radiation therapy in the management of carcinoma of the lung. Carcinoma of the lung is the most common cancer in men in the United States and a major cause of death. This is due to the inadequate techniques for screening of high-risk patients and for detection of the tumor in early stages, before distant dissemination occurs. Although some progress has been made in the past, particularly in improving the knowledge of natural history and pathological characteristics of the disease, and there are better indications for surgical treatment and irradiation and the effective use of cytotoxic agents in selected groups of patients, particularly those with small cell undifferentiated carcinoma, the mortality rate is still very high. A great deal of investigation remains to be done in carcinoma of the lung concerning the basic cell kinetics of the tumor and the optimal conditions for the use of surgery, irradiation, chemotherapy or combinations of these agents in the treatment of these patients before survival rates can be substantially improved. Since the most important factor in patient mortality is distant tumor dissemination, it must be stressed that parameters other than survival should be used to evaluate the effectiveness of irradiation, surgery or combinations in the control of local and regional bronchogenic carcinoma. These efforts should be intensified through properly designed clinical trials."}
{"id": "PMID:189899", "title": "Differential recovery of intestine, bone marrow, and thymus of rats with solid tumors following 5-fluorouracil administration.", "content": "Time relationships for recovery of several host organs from toxic effects of 5-fluorouracil were determined in ACI rats bearing Morris hepatoma 3924A. A single injection of 150 mg/kg body weight 5-fluorouracil (the LD10) resulted in loss of 90% of the tibial bone marrow, 60% of the intestinal mucosa, and 90% of the thymus as measured by total DNA content of the organs. Organ DNA contents following 150 mg/kg of the drug were minimal on day 3 for intestine and on day 5 for marrow and thymus. A return to pretreatment or higher levels of DNA was observed by day 4 for intestine, day 11 for tibial marrow, and day 19 for thymus. Incorporation of 3H-deoxyuridine into host organ DNA after 150 mg/kg 5-fluorouracil was inhibited 36 hrs for intestine, 3 days for thymus, and 5 days for tibial bone marrow. Inhibition of 3H-deoxyuridine incorporation into DNA was similar for 50, 100, and 150 mg/kg doses both in tumor and in host organs, but recovery of 3H-deoxyuridine incorporation and DNA content of host organs began later with the higher doses of 5-fluorouracil. Maximal incorporation of 3H-deoxyuridine into DNA was observed on day 4 for intestine, day 8 for marrow, and day 9 for thymus after treatment with 150 mg/kg 5-fluorouracil. Animal lethality following the second of two 150 mg/kg injections of 5-fluorouracil was related to the extent of recovery of intestinal mucosa and bone marrow at the time of the second injection. Survival decreased to 0% for normal rats when the interval between injections was 3-4 days, improved at 5 days and was 100% when the interval was 10-11 days.", "contents": "Differential recovery of intestine, bone marrow, and thymus of rats with solid tumors following 5-fluorouracil administration. Time relationships for recovery of several host organs from toxic effects of 5-fluorouracil were determined in ACI rats bearing Morris hepatoma 3924A. A single injection of 150 mg/kg body weight 5-fluorouracil (the LD10) resulted in loss of 90% of the tibial bone marrow, 60% of the intestinal mucosa, and 90% of the thymus as measured by total DNA content of the organs. Organ DNA contents following 150 mg/kg of the drug were minimal on day 3 for intestine and on day 5 for marrow and thymus. A return to pretreatment or higher levels of DNA was observed by day 4 for intestine, day 11 for tibial marrow, and day 19 for thymus. Incorporation of 3H-deoxyuridine into host organ DNA after 150 mg/kg 5-fluorouracil was inhibited 36 hrs for intestine, 3 days for thymus, and 5 days for tibial bone marrow. Inhibition of 3H-deoxyuridine incorporation into DNA was similar for 50, 100, and 150 mg/kg doses both in tumor and in host organs, but recovery of 3H-deoxyuridine incorporation and DNA content of host organs began later with the higher doses of 5-fluorouracil. Maximal incorporation of 3H-deoxyuridine into DNA was observed on day 4 for intestine, day 8 for marrow, and day 9 for thymus after treatment with 150 mg/kg 5-fluorouracil. Animal lethality following the second of two 150 mg/kg injections of 5-fluorouracil was related to the extent of recovery of intestinal mucosa and bone marrow at the time of the second injection. Survival decreased to 0% for normal rats when the interval between injections was 3-4 days, improved at 5 days and was 100% when the interval was 10-11 days."}
{"id": "PMID:189900", "title": "Effect of methylazoxymethanol acetate on adenylate cyclase and 5'-nucleotidase in rat liver plasma membranes.", "content": "A single tumorigenic dose of methylazoxymethanol acetate increased adenylate cyclase activity in total liver homogenates 70-100% by the seventh day after treatment. The increased activity occurred in the plasma membranes rather than in the nuclei and was accompanied by a significant increase in 5'-nucleotidase activity. The data indicate that the carcinogen may alter the structure of the plasma membrane.", "contents": "Effect of methylazoxymethanol acetate on adenylate cyclase and 5'-nucleotidase in rat liver plasma membranes. A single tumorigenic dose of methylazoxymethanol acetate increased adenylate cyclase activity in total liver homogenates 70-100% by the seventh day after treatment. The increased activity occurred in the plasma membranes rather than in the nuclei and was accompanied by a significant increase in 5'-nucleotidase activity. The data indicate that the carcinogen may alter the structure of the plasma membrane."}
{"id": "PMID:189901", "title": "Cyclin nucleotide binding sites of the smooth endoplasmic reticulum from normal and neoplastic liver in the rat.", "content": "The studies are presented which demonstrate that smooth endoplasmic membrane of normal liver has a single apparent binding site for cAMP with a KD of 0.6 X 10(-8) M. In contrast to this, however, cyclic AMP binding to the intracellular membrane of hepatoma 7800 exhibit two binding sites; the binding constant of one site on the tumor membrane is comparable to that of the normal liver whereas the value of the second intrinsic association constant differ by a factor of 10. It is suggested that there may be an association between abnormal cyclic nucleotide metabolism and the intracellular membrane modulation of the expression of genetic information in normal and neoplastic cells.", "contents": "Cyclin nucleotide binding sites of the smooth endoplasmic reticulum from normal and neoplastic liver in the rat. The studies are presented which demonstrate that smooth endoplasmic membrane of normal liver has a single apparent binding site for cAMP with a KD of 0.6 X 10(-8) M. In contrast to this, however, cyclic AMP binding to the intracellular membrane of hepatoma 7800 exhibit two binding sites; the binding constant of one site on the tumor membrane is comparable to that of the normal liver whereas the value of the second intrinsic association constant differ by a factor of 10. It is suggested that there may be an association between abnormal cyclic nucleotide metabolism and the intracellular membrane modulation of the expression of genetic information in normal and neoplastic cells."}
{"id": "PMID:189902", "title": "Expression of SV40 T antigen during inhibition of DNA synthesis.", "content": "Treatment of human SV40-transformed cells with excess thymidine or cytosine arabinoside caused a rapid decrease in the expression of T antigen as determined by quantitative immunofluorimetry.", "contents": "Expression of SV40 T antigen during inhibition of DNA synthesis. Treatment of human SV40-transformed cells with excess thymidine or cytosine arabinoside caused a rapid decrease in the expression of T antigen as determined by quantitative immunofluorimetry."}
{"id": "PMID:189903", "title": "Carcinogen-induced DNA repair in primary rat liver cell cultures; a possible screen for chemical carcinogens.", "content": "Primary rat liver cell cultures were exposed to a direct acting carcinogen, methyl methanesulfonate, and procarcinogens requiring metabolic activation, aflatoxin B1 and B2. DNA damage by these agents was evidenced by the induction of DNA repair, measured as unscheduled DNA synthesis. The sensitivity of these cultures to the potent porcarcinogen aflatoxin B1 indicates that this system may be adapted for screening suspected chemical procarcinogens, and for investigating the relationship between metabolic activation of procarcinogens, DNA damage, DNA repair, and carcinogenicity.", "contents": "Carcinogen-induced DNA repair in primary rat liver cell cultures; a possible screen for chemical carcinogens. Primary rat liver cell cultures were exposed to a direct acting carcinogen, methyl methanesulfonate, and procarcinogens requiring metabolic activation, aflatoxin B1 and B2. DNA damage by these agents was evidenced by the induction of DNA repair, measured as unscheduled DNA synthesis. The sensitivity of these cultures to the potent porcarcinogen aflatoxin B1 indicates that this system may be adapted for screening suspected chemical procarcinogens, and for investigating the relationship between metabolic activation of procarcinogens, DNA damage, DNA repair, and carcinogenicity."}
{"id": "PMID:189904", "title": "Carcinogenicity of dimethylnitramine in NZR rats in NZO mice.", "content": "Lifetime tests were done in NZR inbred rats of dimethylnitramine (DMNO) by addition to the drinking water (average dose 1.83 g/kg body weight) and in NZO mice by repeated subcutaneous injection from birth to 7 months of age followed by administration in drinking water (total average dose 4.72 g/kg body weight). Rats developed hepatocellular carcinomas (85%), some of which metastasized. Mice developed hepatocellular carcinomas (81%) and renal adenocarcinomas (48%). Statistically significant increases of other tumor types also occurred in mice. The main targets for DMNO carcinogenesis appeared to be the liver cell epithelium and, at higher dose rates, renal tubular epithelium.", "contents": "Carcinogenicity of dimethylnitramine in NZR rats in NZO mice. Lifetime tests were done in NZR inbred rats of dimethylnitramine (DMNO) by addition to the drinking water (average dose 1.83 g/kg body weight) and in NZO mice by repeated subcutaneous injection from birth to 7 months of age followed by administration in drinking water (total average dose 4.72 g/kg body weight). Rats developed hepatocellular carcinomas (85%), some of which metastasized. Mice developed hepatocellular carcinomas (81%) and renal adenocarcinomas (48%). Statistically significant increases of other tumor types also occurred in mice. The main targets for DMNO carcinogenesis appeared to be the liver cell epithelium and, at higher dose rates, renal tubular epithelium."}
{"id": "PMID:189905", "title": "Enhancement of diethylnitrosamine hepatocarcinogenesis in rats by exposure to polychlorinated biphenyls or phenobarbital.", "content": "Diethylnitrosamine (DENA) hepatocarcinogenesis was enhanced by sequential exposure with polychlorinated biphenyls (PCBs) and with phenobarbital. This was shown by the earlier appearance of tumors and a significant increase in the number of tumors. However, there was no evidence suggesting an acceleration of tumor growth.", "contents": "Enhancement of diethylnitrosamine hepatocarcinogenesis in rats by exposure to polychlorinated biphenyls or phenobarbital. Diethylnitrosamine (DENA) hepatocarcinogenesis was enhanced by sequential exposure with polychlorinated biphenyls (PCBs) and with phenobarbital. This was shown by the earlier appearance of tumors and a significant increase in the number of tumors. However, there was no evidence suggesting an acceleration of tumor growth."}
{"id": "PMID:189906", "title": "Absence of horizontal transmission of herpesvirus saimiri between experimentally infected and noninfected owl monkeys.", "content": "We did not detect cell-free Herpesviurs saimiri (HVS) in the oropharyngeal secretions of owl monkeys with leukemia or lymphoma induced by this virus. These animals failed to transmit either virus or disease to their uninoculated cage-mates or room-mates. Comparison of oropharyngeal secretions of HVS from owl monkeys and squirrel monkeys may provide insight as to how human herpesviruses are maintained in the oropharynx.", "contents": "Absence of horizontal transmission of herpesvirus saimiri between experimentally infected and noninfected owl monkeys. We did not detect cell-free Herpesviurs saimiri (HVS) in the oropharyngeal secretions of owl monkeys with leukemia or lymphoma induced by this virus. These animals failed to transmit either virus or disease to their uninoculated cage-mates or room-mates. Comparison of oropharyngeal secretions of HVS from owl monkeys and squirrel monkeys may provide insight as to how human herpesviruses are maintained in the oropharynx."}
{"id": "PMID:189907", "title": "Comparison of the effects of 6- thio- and 6-methylthiopurine ribonucleoside cyclic monophosphates withtheir corresponding nucleosides on the growth of rat hepatoma cells.", "content": "The cyclic nucleotide forms of 6-mercaptopurine and 6-methylmercaptopurine have been found to be cytotoxic to rat hepatoma cells. Studies with an inhibitor of phosphodiesterase suggest that the cytotoxicity of both cyclic nucleotides results principally from conversion to the 5'-nucleotide. A comparison of the two thiopurine cyclic nucleotides with their nucleoside counterparts has suggested that (a) the thio derivatives act by a common mechanism which is different from that exerted by the methylthio derivatives, and (b) the methylthio cyclic nucleotide acts, at least in part, by a mechanism which differs from that exerted by the methylthio nucleoside.", "contents": "Comparison of the effects of 6- thio- and 6-methylthiopurine ribonucleoside cyclic monophosphates withtheir corresponding nucleosides on the growth of rat hepatoma cells. The cyclic nucleotide forms of 6-mercaptopurine and 6-methylmercaptopurine have been found to be cytotoxic to rat hepatoma cells. Studies with an inhibitor of phosphodiesterase suggest that the cytotoxicity of both cyclic nucleotides results principally from conversion to the 5'-nucleotide. A comparison of the two thiopurine cyclic nucleotides with their nucleoside counterparts has suggested that (a) the thio derivatives act by a common mechanism which is different from that exerted by the methylthio derivatives, and (b) the methylthio cyclic nucleotide acts, at least in part, by a mechanism which differs from that exerted by the methylthio nucleoside."}
{"id": "PMID:189908", "title": "The effect of the phorbol ester tumor promoters on the basal and catecholamine-stimulated levels of cyclic adenosine 3':5'-monophosphate in mouse skin and epidermis in vivo.", "content": "To measure the in vivo levels of cyclic adenosine 3':5'-monophosphate (cyclic AMP) in mouse skin, precautions must be taken to avoid artifactual alterations after excision of the skin from the mouse. With such precautions, the level of cyclic AMP in mouse epidermal-dermal preparations was unchanged 1 to 18 hr after application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin. The accumulation of cyclic AMP in response to isoproterenol or the naturally occurring catecholamine epinephrine was, however, significantly diminished 9 to 24 hr after application of TPA. No enhanced accumulation of cyclic AMP in response to alpha-adrenergic stimulation accompanied this diminished beta-adrenergic responsiveness. Experiments with pure epidermis confirmed that these observations reflected the effects of TPA on the epidermal cells in the epidermal-dermal preparations. The metabolism of isoproterenol in TPA-treated epidermis was the same as that in control epidermis. Finally, the tumor-promoting activity of various doses of TPA and of other phorbol esters correlated with their ability to diminish the beta-adrenergic responsiveness of the epidermis.", "contents": "The effect of the phorbol ester tumor promoters on the basal and catecholamine-stimulated levels of cyclic adenosine 3':5'-monophosphate in mouse skin and epidermis in vivo. To measure the in vivo levels of cyclic adenosine 3':5'-monophosphate (cyclic AMP) in mouse skin, precautions must be taken to avoid artifactual alterations after excision of the skin from the mouse. With such precautions, the level of cyclic AMP in mouse epidermal-dermal preparations was unchanged 1 to 18 hr after application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin. The accumulation of cyclic AMP in response to isoproterenol or the naturally occurring catecholamine epinephrine was, however, significantly diminished 9 to 24 hr after application of TPA. No enhanced accumulation of cyclic AMP in response to alpha-adrenergic stimulation accompanied this diminished beta-adrenergic responsiveness. Experiments with pure epidermis confirmed that these observations reflected the effects of TPA on the epidermal cells in the epidermal-dermal preparations. The metabolism of isoproterenol in TPA-treated epidermis was the same as that in control epidermis. Finally, the tumor-promoting activity of various doses of TPA and of other phorbol esters correlated with their ability to diminish the beta-adrenergic responsiveness of the epidermis."}
{"id": "PMID:189909", "title": "Inhibition of macrophage chemotaxis by neoplastic and other rapidly proliferating cells in vitro.", "content": "Culture supernatants from rapidly proliferating cell lines inhibit macrophage chemotaxis. Of the cell lines tested, the supernatant from polyoma virus-induced tumor cells was the strongest inhibitor, although supernatants from simian virus 40-transformed 3T3, dimethylbenzanthracene-induced tumor cells, and Chinease hamster ovary fibroblasts also possessed inhibitory activity. The inhibitory substance(s) bound onto the macrophage cell surface. Although none of the culture supernatants examined were chemotactic for rat macrophages, they did possess weak attractive activity for polymorphonuclear neutrophils. This capacity of rapidly growing cells in culture to generate substances inhibitory to macrophage chemotaxis while attracting polymorphonuclear neutrophils may be relevant to the mechanism by which tumor bearing in vivo produces a cell-specific defect in chronic but not acute inflammation.", "contents": "Inhibition of macrophage chemotaxis by neoplastic and other rapidly proliferating cells in vitro. Culture supernatants from rapidly proliferating cell lines inhibit macrophage chemotaxis. Of the cell lines tested, the supernatant from polyoma virus-induced tumor cells was the strongest inhibitor, although supernatants from simian virus 40-transformed 3T3, dimethylbenzanthracene-induced tumor cells, and Chinease hamster ovary fibroblasts also possessed inhibitory activity. The inhibitory substance(s) bound onto the macrophage cell surface. Although none of the culture supernatants examined were chemotactic for rat macrophages, they did possess weak attractive activity for polymorphonuclear neutrophils. This capacity of rapidly growing cells in culture to generate substances inhibitory to macrophage chemotaxis while attracting polymorphonuclear neutrophils may be relevant to the mechanism by which tumor bearing in vivo produces a cell-specific defect in chronic but not acute inflammation."}
{"id": "PMID:189910", "title": "Transformation of chicken chondrocytes by Rous sarcoma virus.", "content": "Chicken chondrocytes isolated from 11-day-old chicken vertebrate cartilage were transformed by Rous sarcoma virus ts LA24 of the Prague strain as well as by the wild-type Prague strain of Rous sarcoma virus. The morphology of chondrocytes transformed by Rous sarcoma virus ts LA 24 was dependent on the temperature, and the change was reversible. A similar but irreversible change in morphology was observed with chondrocytes transformed by wild-type virus. Hyaluronic acid production and deoxyglucose transport were markedly increased in the transformed chondrocytes. A marked increase of labeled acetate incorporation was observed with the transformed chondrocytes. In contrast to the normal chondrocytes, the labeled hyaluronic acid synthesized by the transformed chondrocytes was mostly released into the culture medium.", "contents": "Transformation of chicken chondrocytes by Rous sarcoma virus. Chicken chondrocytes isolated from 11-day-old chicken vertebrate cartilage were transformed by Rous sarcoma virus ts LA24 of the Prague strain as well as by the wild-type Prague strain of Rous sarcoma virus. The morphology of chondrocytes transformed by Rous sarcoma virus ts LA 24 was dependent on the temperature, and the change was reversible. A similar but irreversible change in morphology was observed with chondrocytes transformed by wild-type virus. Hyaluronic acid production and deoxyglucose transport were markedly increased in the transformed chondrocytes. A marked increase of labeled acetate incorporation was observed with the transformed chondrocytes. In contrast to the normal chondrocytes, the labeled hyaluronic acid synthesized by the transformed chondrocytes was mostly released into the culture medium."}
{"id": "PMID:189911", "title": "Differential neurooncogenicity of strains of JC virus, a human polyoma virus, in newborn Syrian hamsters.", "content": "The neurooncogenicity recently isolated strains of the human polyoma virus, JC virus, was determined by intracerebral inoculation of newborn Syrian golden hamsters. All three strains produced malignant brain tumors in a majority of inoculated animals during a 6.5-month observation period. The results obtained with the MAD-2 strain, 19 of 20 animals with cerebellar medulloblastomas and 0 of 20 animals with pineal gland tumors, were quite similar to those observed previously with the prototypic strain of JC virus, MAD-1. Inoculation of the MAD-4 strain, however, resulted in 10 of 22 animals with pineal gland tumors and only 10 of 22 animals with tumors in the cerebellum. The MAD-3 strain was neurooncogenic, but too few animals lived to be weaned to provide significant additional information. The basis for the apparent predilection of the MAD-4 strain for the pineal gland is unknown. Two hamsters in the experiment developed extracranial neuroblastomas.", "contents": "Differential neurooncogenicity of strains of JC virus, a human polyoma virus, in newborn Syrian hamsters. The neurooncogenicity recently isolated strains of the human polyoma virus, JC virus, was determined by intracerebral inoculation of newborn Syrian golden hamsters. All three strains produced malignant brain tumors in a majority of inoculated animals during a 6.5-month observation period. The results obtained with the MAD-2 strain, 19 of 20 animals with cerebellar medulloblastomas and 0 of 20 animals with pineal gland tumors, were quite similar to those observed previously with the prototypic strain of JC virus, MAD-1. Inoculation of the MAD-4 strain, however, resulted in 10 of 22 animals with pineal gland tumors and only 10 of 22 animals with tumors in the cerebellum. The MAD-3 strain was neurooncogenic, but too few animals lived to be weaned to provide significant additional information. The basis for the apparent predilection of the MAD-4 strain for the pineal gland is unknown. Two hamsters in the experiment developed extracranial neuroblastomas."}
{"id": "PMID:189912", "title": "A discrepancy in XC and oncogenicity assays for murine leukemia virus in AKR mice.", "content": "Studies of murine leukemia virus expression in AKR mice are presented. Material from in vivo and in vitro sources of normal tissues and lymphomas was assayed for in vitro infectivity, using the XC plaque assay, and for oncogenicity, by assessing lymphoma-accelerating capacity after inoculation into newborn animals. Normal tissues from healthy young AKR mice up to 7 months of age were found to have XC but not oncogenic activity. XC activity persisted, and weak oncogenic activity appeared in older mice. Cocultivation of normal young cells with NIH Swiss mouse embryo cells did not result in the appearance of oncogenic activity, although XC virus increased in titer. A cell-free filtrate of a virus-accelerated lymphoma was studied for host range. Virus as measured by polymerase and gs antigen was found to be propagated on NIH Swiss mouse embryo and wild mouse embryo cells, but not on human rhabdomyosarcoma, normal rat kidney, rabbit corneal, and BALB/c embryo cells. Virus as measured by the XC assay grew better on NIH Swiss mouse than on BALB/c embryo cells. Both of these cell lines propagated virus as measured by the oncogenicity assay. Supernatants from an in vitro cell line from a virus-accelerated lymphoma did not produce XC plaques but were oncogenic. Those from two cell lines of spontaneous lymphomas were negative with both assays. Cultivation of supernatants from these cultured lymphoma cells with NIH Swiss mouse embryo cells resulted in material which produced small plaques on the XC assay. These findings are interpreted as showing the presence of two viruses in AKR mice. One is XC positive and present throughout life. The other is oncogenic, appears later in life, and could be a separate virus or a variant of the first one.", "contents": "A discrepancy in XC and oncogenicity assays for murine leukemia virus in AKR mice. Studies of murine leukemia virus expression in AKR mice are presented. Material from in vivo and in vitro sources of normal tissues and lymphomas was assayed for in vitro infectivity, using the XC plaque assay, and for oncogenicity, by assessing lymphoma-accelerating capacity after inoculation into newborn animals. Normal tissues from healthy young AKR mice up to 7 months of age were found to have XC but not oncogenic activity. XC activity persisted, and weak oncogenic activity appeared in older mice. Cocultivation of normal young cells with NIH Swiss mouse embryo cells did not result in the appearance of oncogenic activity, although XC virus increased in titer. A cell-free filtrate of a virus-accelerated lymphoma was studied for host range. Virus as measured by polymerase and gs antigen was found to be propagated on NIH Swiss mouse embryo and wild mouse embryo cells, but not on human rhabdomyosarcoma, normal rat kidney, rabbit corneal, and BALB/c embryo cells. Virus as measured by the XC assay grew better on NIH Swiss mouse than on BALB/c embryo cells. Both of these cell lines propagated virus as measured by the oncogenicity assay. Supernatants from an in vitro cell line from a virus-accelerated lymphoma did not produce XC plaques but were oncogenic. Those from two cell lines of spontaneous lymphomas were negative with both assays. Cultivation of supernatants from these cultured lymphoma cells with NIH Swiss mouse embryo cells resulted in material which produced small plaques on the XC assay. These findings are interpreted as showing the presence of two viruses in AKR mice. One is XC positive and present throughout life. The other is oncogenic, appears later in life, and could be a separate virus or a variant of the first one."}
{"id": "PMID:189913", "title": "Interaction of amphotericin B and 43 degrees hyperthermia.", "content": "At 43 degrees (but not at 41 degrees), the polyene antibiotic amphotericin B effectively inactivates mammalian cells in vitro even at doses which are used prophylactically, routinely, and continuously in some tissue culture laboratories. The greatly enhanced killing may reflect interactions between the drug and hyperthermia at the level of the cells' plasma membrane. A similar enhancement of cell killing at 43 degrees was seen when cells were exposed to nonisotonic salt solutions. Another polyene, nystatin, shows no temperature dependence, at least over the dose range examined, while another antifungal agent, polymyxin B, does so only at very high doses. The in vitro thermosensibility of cells to amphotericin B is reflected in vivo: EMT-6 murine tumor cells were killed much more efficiently in situ at 43 than at 37 degrees. Amphotericin B may be a useful agent in multiple drug thermochemotherapy.", "contents": "Interaction of amphotericin B and 43 degrees hyperthermia. At 43 degrees (but not at 41 degrees), the polyene antibiotic amphotericin B effectively inactivates mammalian cells in vitro even at doses which are used prophylactically, routinely, and continuously in some tissue culture laboratories. The greatly enhanced killing may reflect interactions between the drug and hyperthermia at the level of the cells' plasma membrane. A similar enhancement of cell killing at 43 degrees was seen when cells were exposed to nonisotonic salt solutions. Another polyene, nystatin, shows no temperature dependence, at least over the dose range examined, while another antifungal agent, polymyxin B, does so only at very high doses. The in vitro thermosensibility of cells to amphotericin B is reflected in vivo: EMT-6 murine tumor cells were killed much more efficiently in situ at 43 than at 37 degrees. Amphotericin B may be a useful agent in multiple drug thermochemotherapy."}
{"id": "PMID:189914", "title": "Kinetics of hormone-induced tumor cell resistance to killing by antibody and complement.", "content": "Line 1, a chemically induced guinea pig hepatoma, is susceptible to killing by anti-Forssman immunoglobulin M antibody and guinea pig complement. When these tumor cells are pretreated with insulin, L-epinephrine, hydrocortisone, or prednisolone, the cells show a marked reduction in their susceptibility to antibody-complement-mediated killing within 15 to 60 min; this effect reverses within 4 hr in the continued presence of hormone. Maximal binding of the hormones to the line 1 cells was observed within 60 min. However, the hormones remained bound to the cells after 4 hr of incubation, suggesting that line 1 cells incubated in the continued presence of hormone revert to the susceptible state despite the persistence of cell-bound hormone. Hormone-treated tumor cells, washed free of hormone and reincubated in hormone-free medium, lost nearly all their bound hormone within 15 to 30 min of washing. These cells, however, remained resistant to antibody-complement-mediated killing for up to 2 hr after washing. Line 1 cells, reverted in the continued presence of hormone, remained susceptible to killing by antibody and guinea pig complement after reexposure to the same, but not to a different, hormone. Hormone-treated cells reverted after prolonged incubation in hormone-free media; however, they were rendered resistant to killing after reexposure to the same hormone. The temporary refractoriness of reverted cells to further hormone stimulation was not due to an inability of the cells to bind hormone.", "contents": "Kinetics of hormone-induced tumor cell resistance to killing by antibody and complement. Line 1, a chemically induced guinea pig hepatoma, is susceptible to killing by anti-Forssman immunoglobulin M antibody and guinea pig complement. When these tumor cells are pretreated with insulin, L-epinephrine, hydrocortisone, or prednisolone, the cells show a marked reduction in their susceptibility to antibody-complement-mediated killing within 15 to 60 min; this effect reverses within 4 hr in the continued presence of hormone. Maximal binding of the hormones to the line 1 cells was observed within 60 min. However, the hormones remained bound to the cells after 4 hr of incubation, suggesting that line 1 cells incubated in the continued presence of hormone revert to the susceptible state despite the persistence of cell-bound hormone. Hormone-treated tumor cells, washed free of hormone and reincubated in hormone-free medium, lost nearly all their bound hormone within 15 to 30 min of washing. These cells, however, remained resistant to antibody-complement-mediated killing for up to 2 hr after washing. Line 1 cells, reverted in the continued presence of hormone, remained susceptible to killing by antibody and guinea pig complement after reexposure to the same, but not to a different, hormone. Hormone-treated cells reverted after prolonged incubation in hormone-free media; however, they were rendered resistant to killing after reexposure to the same hormone. The temporary refractoriness of reverted cells to further hormone stimulation was not due to an inability of the cells to bind hormone."}
{"id": "PMID:189915", "title": "Effect of prolactin on growth and the estrogen receptor level of human breast cancer cells (MCF-7).", "content": "The intracellular specific 17beta-estradiol binding in the human breast cancer cell line, MCF-7, was shown to be modified by prolactin. Both ovine and human prolactin doubled the estradiol receptor (E2R) level, but the latter was at least 10 times more stimulatory on a concentration basis. Most of the E2R complex (approximately 80%) was transported to the nucleus, and the prolactin stimulation was reflected in an elevated nuclear uptake of the tritiated 17beta-estradiol. Neither ovine nor human prolactin altered the growth rate of the cells when E2R stimulation was maximal. Insulin (10 mug/ml) stimulated tritiated thymidine incorporation and total DNA content but had no apparent effect on E2R concentration. At 10(-4) M, N6,O2'-dibutyrylcyclicadenosine 3':5'-monophosphate increased insulin stimulation of tritiated thymidine incorporation and brought about a prolactin stimulation of apparent DNA synthesis. Theophylline (10(-3) M) blocked both of these effects of N6,O2'-dibutyrylcyclicadenosine 3':5'-monophosphate. The possible mechanism implicating prolactin as an effector of differentiation and growth of MCF-7 cells is discussed.", "contents": "Effect of prolactin on growth and the estrogen receptor level of human breast cancer cells (MCF-7). The intracellular specific 17beta-estradiol binding in the human breast cancer cell line, MCF-7, was shown to be modified by prolactin. Both ovine and human prolactin doubled the estradiol receptor (E2R) level, but the latter was at least 10 times more stimulatory on a concentration basis. Most of the E2R complex (approximately 80%) was transported to the nucleus, and the prolactin stimulation was reflected in an elevated nuclear uptake of the tritiated 17beta-estradiol. Neither ovine nor human prolactin altered the growth rate of the cells when E2R stimulation was maximal. Insulin (10 mug/ml) stimulated tritiated thymidine incorporation and total DNA content but had no apparent effect on E2R concentration. At 10(-4) M, N6,O2'-dibutyrylcyclicadenosine 3':5'-monophosphate increased insulin stimulation of tritiated thymidine incorporation and brought about a prolactin stimulation of apparent DNA synthesis. Theophylline (10(-3) M) blocked both of these effects of N6,O2'-dibutyrylcyclicadenosine 3':5'-monophosphate. The possible mechanism implicating prolactin as an effector of differentiation and growth of MCF-7 cells is discussed."}
{"id": "PMID:189916", "title": "Urea synthesis in Novikoff and Morris hepatomas.", "content": "The rates of urea synthesis in rat liver and in a series of rat liver neoplasms with widely different growth rates and degree of differentiation were investigated using tissue slices incubated in a Krebs-Ringer bicarbonate buffer. Urea synthesis did not occur in fast-growing, poorly differentiated Novikoff and Morris 3924A hepatomas, but it did occur in slow-growing, well- and highly differentiated hepatomas; however, there was no correlation with growth rate or degree of differentiation. Urea synthesis was comparable with normal liver, at about 32 mumoles/hr/g tissue, in the slow-growing Morris hepatomas 21, 28A, 47C, and 44; but it was very low in two other slow-growing, highly differentiated hepatomas, 9618A and 20. The well-differentiated Morris hepatoma 5123C had intermediate levels of urea synthesis. This pattern of urea synthesis closely paralleled the previously reported activity of carbamyl phosphate synthetase in these tumors. The rate of urea synthesis was normal in livers of Buffalo rats bearing fast- or slow-growing hepatomas in low urea synthesis rates, but it was markedly lowered in the livers of rats bearing large, slow-growing tumors with high urea synthesis rates. Urea synthesis in liver declined as the tumors increased in size. The total rate of urea synthesis in liver and tumor, as well as the concentrations of urea in the serum and urine of tumor-bearing animals, remained remarkably constant throughout the period of tumor growth, suggesting the existence of a homeostatic mechanism that controls the urea cycle activity in accordance with the synthetic activity of the tumor. In parabiotic animals, carbamyl phosphate synthetase activity and urea synthesis were lowered in the host livers of partners bearing tumors with high carbamyl phosphate synthetase- and urea-synthetic activity, but there was no significant effect on urea cycle activity in the normal partners. This result discounts the likelihood of a circulating humoral factor that controls hepatic urea cycle activity.", "contents": "Urea synthesis in Novikoff and Morris hepatomas. The rates of urea synthesis in rat liver and in a series of rat liver neoplasms with widely different growth rates and degree of differentiation were investigated using tissue slices incubated in a Krebs-Ringer bicarbonate buffer. Urea synthesis did not occur in fast-growing, poorly differentiated Novikoff and Morris 3924A hepatomas, but it did occur in slow-growing, well- and highly differentiated hepatomas; however, there was no correlation with growth rate or degree of differentiation. Urea synthesis was comparable with normal liver, at about 32 mumoles/hr/g tissue, in the slow-growing Morris hepatomas 21, 28A, 47C, and 44; but it was very low in two other slow-growing, highly differentiated hepatomas, 9618A and 20. The well-differentiated Morris hepatoma 5123C had intermediate levels of urea synthesis. This pattern of urea synthesis closely paralleled the previously reported activity of carbamyl phosphate synthetase in these tumors. The rate of urea synthesis was normal in livers of Buffalo rats bearing fast- or slow-growing hepatomas in low urea synthesis rates, but it was markedly lowered in the livers of rats bearing large, slow-growing tumors with high urea synthesis rates. Urea synthesis in liver declined as the tumors increased in size. The total rate of urea synthesis in liver and tumor, as well as the concentrations of urea in the serum and urine of tumor-bearing animals, remained remarkably constant throughout the period of tumor growth, suggesting the existence of a homeostatic mechanism that controls the urea cycle activity in accordance with the synthetic activity of the tumor. In parabiotic animals, carbamyl phosphate synthetase activity and urea synthesis were lowered in the host livers of partners bearing tumors with high carbamyl phosphate synthetase- and urea-synthetic activity, but there was no significant effect on urea cycle activity in the normal partners. This result discounts the likelihood of a circulating humoral factor that controls hepatic urea cycle activity."}
{"id": "PMID:189917", "title": "The undifferentiated enzymic composition of human fetal lung and pulmonary tumors.", "content": "The concentrations of 16 to 21 enzymes, representing various metabolic pathways, have been determined in human adult, fetal, and neoplastic lung. At midgestation, 12 enzymes (among them, several that metabolize amino acids) were above their adult values while 3 other enzymes were still at low concentrations. These signs of biochemical immaturity are contrasted and compared with those in fetal human liver and rat lung. The enzymic composition of the 11 human pulmonary tumors studied resembled that of the normal fetal lungs closely; the same 12 enzymes were elevated and the same 2 were decreased (compared to nonneoplastic adult lung) in both. The characteristic abnormality in the overall pattern of enzymes, in the concentrations of individual ones, and in the quality of pyrroline-5-carboxylate reductase was clearly evident in both primary and metastatic tumors. The mean concentrations of 10 enzymes in the tumors were significantly different (higher or lower) from those in the control lungs (p less than 0.001 to less than 0.05). The best markers of neoplasticity were thymidine kinase, peptidyl proline hydroxylase, phosphoserine phosphatase, hexokinase, and pyrroline-5-carboxylate reductase. The results demonstrate that quantification of a small battery of enzymes, none of them tissue specific, can distinguish adult human lung from its neoplasms.", "contents": "The undifferentiated enzymic composition of human fetal lung and pulmonary tumors. The concentrations of 16 to 21 enzymes, representing various metabolic pathways, have been determined in human adult, fetal, and neoplastic lung. At midgestation, 12 enzymes (among them, several that metabolize amino acids) were above their adult values while 3 other enzymes were still at low concentrations. These signs of biochemical immaturity are contrasted and compared with those in fetal human liver and rat lung. The enzymic composition of the 11 human pulmonary tumors studied resembled that of the normal fetal lungs closely; the same 12 enzymes were elevated and the same 2 were decreased (compared to nonneoplastic adult lung) in both. The characteristic abnormality in the overall pattern of enzymes, in the concentrations of individual ones, and in the quality of pyrroline-5-carboxylate reductase was clearly evident in both primary and metastatic tumors. The mean concentrations of 10 enzymes in the tumors were significantly different (higher or lower) from those in the control lungs (p less than 0.001 to less than 0.05). The best markers of neoplasticity were thymidine kinase, peptidyl proline hydroxylase, phosphoserine phosphatase, hexokinase, and pyrroline-5-carboxylate reductase. The results demonstrate that quantification of a small battery of enzymes, none of them tissue specific, can distinguish adult human lung from its neoplasms."}
{"id": "PMID:189918", "title": "Uridine triphosphate deficiency, growth inhibition, and death in ascites hepatoma cells induced by a combination of pyrimidine biosynthesis inhibition with uridylate trapping.", "content": "A selective deficiency of uridine triphosphate (UTP) was induced in AS-30D rat ascites hepatoma cells by the synergistic action of D-galactosamine and 6-azauridine. The resistance of these hepatoma cells to low concentrations of D-galactosamine (less than 2 mM) was due to their active de novo pyrimidine synthesis which compensated the trapping of uridylate in the form of uridine diphosphate-amino sugars derived from D-galactosamine. The additional blockage of de novo pyrimidine synthesis led to noncompensated uridylate trapping with a UTP content of less than 0.05 mmole/kg of cell wet weight as compared to the control level of 0.66 mmole/kg. The induction of UTP deficiency by incubating the cells with low concentrations of D-galactosamine and 6-azauridine (0.5 mM each) was not accompanied by significant changes in the content of adenine and guanine nucleotides, uridine diphosphate glucose, and uridine diphosphate galactose. The depletion of UTP pools could be reversed within 10 min by the addition of uridine; orotate or uracil were completely ineffective in these hepatoma cells. A UTP content in the range of 0.1 to 0.4 mmole/kg, induced by either 6-azauridine or D-galactosamine, was associated with a reversible depression of cell growth in suspension culture. A UTP content below 0.05 mmole/kg led to irreversible growth inhibition and to necrocytosis in culture, as well as to a loss of transplantability in vivo. Uridine reversal studies indicated that the percentage of cells able to resume growth in culture decreased with an increasing time period of UTP deficiency. The deficiency period required for irreparable or lethal damage in these hepatoma cells ranged from 3 to 20 hr. The principle of noncompensated uridylate trapping can be extended to other inhibitors of nucleotide synthesis combined with various nucleotide-trapping sugar analogs. Noncompensated nucleotide trapping may be useful for an induction of selective nucleotide deficiencies in tumor cells.", "contents": "Uridine triphosphate deficiency, growth inhibition, and death in ascites hepatoma cells induced by a combination of pyrimidine biosynthesis inhibition with uridylate trapping. A selective deficiency of uridine triphosphate (UTP) was induced in AS-30D rat ascites hepatoma cells by the synergistic action of D-galactosamine and 6-azauridine. The resistance of these hepatoma cells to low concentrations of D-galactosamine (less than 2 mM) was due to their active de novo pyrimidine synthesis which compensated the trapping of uridylate in the form of uridine diphosphate-amino sugars derived from D-galactosamine. The additional blockage of de novo pyrimidine synthesis led to noncompensated uridylate trapping with a UTP content of less than 0.05 mmole/kg of cell wet weight as compared to the control level of 0.66 mmole/kg. The induction of UTP deficiency by incubating the cells with low concentrations of D-galactosamine and 6-azauridine (0.5 mM each) was not accompanied by significant changes in the content of adenine and guanine nucleotides, uridine diphosphate glucose, and uridine diphosphate galactose. The depletion of UTP pools could be reversed within 10 min by the addition of uridine; orotate or uracil were completely ineffective in these hepatoma cells. A UTP content in the range of 0.1 to 0.4 mmole/kg, induced by either 6-azauridine or D-galactosamine, was associated with a reversible depression of cell growth in suspension culture. A UTP content below 0.05 mmole/kg led to irreversible growth inhibition and to necrocytosis in culture, as well as to a loss of transplantability in vivo. Uridine reversal studies indicated that the percentage of cells able to resume growth in culture decreased with an increasing time period of UTP deficiency. The deficiency period required for irreparable or lethal damage in these hepatoma cells ranged from 3 to 20 hr. The principle of noncompensated uridylate trapping can be extended to other inhibitors of nucleotide synthesis combined with various nucleotide-trapping sugar analogs. Noncompensated nucleotide trapping may be useful for an induction of selective nucleotide deficiencies in tumor cells."}
{"id": "PMID:189919", "title": "Inhibition of leukocyte migration by tumor-associated antigen in soluble extracts of human hepatoma.", "content": "The leukocyte migration inhibition assay was used to detect cell-mediated immune reaction of hepatoma patients. Extraction of 3 pairs of human hepatoma tissue and normal liver tissue was made by 3 M KCI solution, and soluble hepatoma antigens were used to test against leukocytes of 18 hepatoma patients by the leukocyte migration inhibition assay. In all, 25 tests were performed; most of them were allogenic, and only 3 tests were autologous. Migration inhibition was observed in 13 of 25 tests, and there were only a few cases of migration inhibition in the control groups. It was concluded that tumor-associated antigen of human hepatoma was contained in the 3 M KCI extract of hepatoma tissue and that tumor-associated antigen of human hepatoma was shared by some hepatoma patients.", "contents": "Inhibition of leukocyte migration by tumor-associated antigen in soluble extracts of human hepatoma. The leukocyte migration inhibition assay was used to detect cell-mediated immune reaction of hepatoma patients. Extraction of 3 pairs of human hepatoma tissue and normal liver tissue was made by 3 M KCI solution, and soluble hepatoma antigens were used to test against leukocytes of 18 hepatoma patients by the leukocyte migration inhibition assay. In all, 25 tests were performed; most of them were allogenic, and only 3 tests were autologous. Migration inhibition was observed in 13 of 25 tests, and there were only a few cases of migration inhibition in the control groups. It was concluded that tumor-associated antigen of human hepatoma was contained in the 3 M KCI extract of hepatoma tissue and that tumor-associated antigen of human hepatoma was shared by some hepatoma patients."}
{"id": "PMID:189920", "title": "Cyclophosphamide, adriamycin, methotrexate, and procarbazine (CAMP)--effective four-drug combination chemotherapy for metastatic non-oat cell bronchogenic carcinoma.", "content": "Twenty-three patients with metastatic non-oat cell bronchogenic carcinoma (MNOBC) were treated with cyclophosphamide, adriamycin, methotrexate, and procarbazine (CAMP) after radiation therapy. Objective responses were seen in 11 of 23 patients (48%) with a projected median survival time of 12.5 months for responding patients and patients with stable disease. Lung, liver, and cutaneous sites of involvement proved to be highly responsive; bone involvement was less responsive. CAMP is an effective combination in the treatment of MNOBC and its use in patients with less advanced disease should be explored.", "contents": "Cyclophosphamide, adriamycin, methotrexate, and procarbazine (CAMP)--effective four-drug combination chemotherapy for metastatic non-oat cell bronchogenic carcinoma. Twenty-three patients with metastatic non-oat cell bronchogenic carcinoma (MNOBC) were treated with cyclophosphamide, adriamycin, methotrexate, and procarbazine (CAMP) after radiation therapy. Objective responses were seen in 11 of 23 patients (48%) with a projected median survival time of 12.5 months for responding patients and patients with stable disease. Lung, liver, and cutaneous sites of involvement proved to be highly responsive; bone involvement was less responsive. CAMP is an effective combination in the treatment of MNOBC and its use in patients with less advanced disease should be explored."}
{"id": "PMID:189921", "title": "Phase II study of vinblastine, adriamycin, and procarbazine in small cell carcinoma of the lung.", "content": "Twenty-four patients with small cell carcinoma of the lung were treated with a combination of vinblastine, 5 mg/m2 iv on Day 1; adriamycin, 40 mg/m2 iv on Day 1; and procarbazine, 100 mg/m2 orally on Days 1-7. The courses were repeated every 21 days. Tumor regression was noted in five of eight previously untreated patients, in two of six patients with previous chemotherapy, and in one of ten patients with previous chemotherapy and irradiation. The median duration of response was 130 days (range, 42-488+ days). The major toxic effects were bone marrow depression, gastrointestinal disturbances, and alopecia. This drug combination deserves consideration for inclusion into sequential combination chemotherapy regimens used in the treatment of this tumor type.", "contents": "Phase II study of vinblastine, adriamycin, and procarbazine in small cell carcinoma of the lung. Twenty-four patients with small cell carcinoma of the lung were treated with a combination of vinblastine, 5 mg/m2 iv on Day 1; adriamycin, 40 mg/m2 iv on Day 1; and procarbazine, 100 mg/m2 orally on Days 1-7. The courses were repeated every 21 days. Tumor regression was noted in five of eight previously untreated patients, in two of six patients with previous chemotherapy, and in one of ten patients with previous chemotherapy and irradiation. The median duration of response was 130 days (range, 42-488+ days). The major toxic effects were bone marrow depression, gastrointestinal disturbances, and alopecia. This drug combination deserves consideration for inclusion into sequential combination chemotherapy regimens used in the treatment of this tumor type."}
{"id": "PMID:189928", "title": "Neuronal cytoplasmic inclusions in the dorsal horn and supraoptic nucleus of the squirrel monkey, Saimiri sciureus.", "content": "In the squirrel monkey (Saimiri sciureus) two types of cytoplasmic inclusion bodies have been observed sporadically in neurons of both the dorsal horn (Rexed's laminae I-III in the lumbosacral region) and the supraoptic nucleus. One of these, designated here the \"vesicular body\", is a round inclusion which measures up to 1.4 mu in diameter. It occurs only in perikarya and is composed of vesicular-like chambers 300-400 A in diameter. We have not found previous references to this structure in the literature, but its 50 A substructural particles are similar in size to those described in nematosomes. The other inclusion, a \"filamentous whorl\", is found in nerve cell bodies and dendrites and it is structurally similar to the Hirano body. The structure measures up to 2.2 mu in diameter and is composed of circularly arrayed filaments which vary in configuration and size depending on the plane of section. There are no indications that the vesicular body and the filamentous whorl are in any way related to each other; and usually both are not found in the same cell profiles.", "contents": "Neuronal cytoplasmic inclusions in the dorsal horn and supraoptic nucleus of the squirrel monkey, Saimiri sciureus. In the squirrel monkey (Saimiri sciureus) two types of cytoplasmic inclusion bodies have been observed sporadically in neurons of both the dorsal horn (Rexed's laminae I-III in the lumbosacral region) and the supraoptic nucleus. One of these, designated here the \"vesicular body\", is a round inclusion which measures up to 1.4 mu in diameter. It occurs only in perikarya and is composed of vesicular-like chambers 300-400 A in diameter. We have not found previous references to this structure in the literature, but its 50 A substructural particles are similar in size to those described in nematosomes. The other inclusion, a \"filamentous whorl\", is found in nerve cell bodies and dendrites and it is structurally similar to the Hirano body. The structure measures up to 2.2 mu in diameter and is composed of circularly arrayed filaments which vary in configuration and size depending on the plane of section. There are no indications that the vesicular body and the filamentous whorl are in any way related to each other; and usually both are not found in the same cell profiles."}
{"id": "PMID:189929", "title": "Unusual presynaptic inclusions in the CNS of the marine polychaete, Nereis virens.", "content": "Unusual electron-dense inclusions occur in the nerve terminals of the Nereis CNS. These structures are closely associated with synaptic vesicles and contain what appear to be incomplete vesicles within them suggesting that they may be an organelle involved in synaptic vesicle production.", "contents": "Unusual presynaptic inclusions in the CNS of the marine polychaete, Nereis virens. Unusual electron-dense inclusions occur in the nerve terminals of the Nereis CNS. These structures are closely associated with synaptic vesicles and contain what appear to be incomplete vesicles within them suggesting that they may be an organelle involved in synaptic vesicle production."}
{"id": "PMID:189930", "title": "The ultrastructure of the mid-gut cells of Nasonia vitripennis (Walker) (Hymenoptera, Pteromalidae).", "content": "The ultrastructure of the mid-gut cells of female Nasonia vitripennis is described. The mid-gut consists of a uniform, single-cell epithelium. The cells of different gut regions were analysed using morphometric techniques in order to determine any differences in the components. The structure of the cells is described in the unfed animal, and after varying periods of feeding on host body-fluids. Tissues were sampled after 12 h and 24 h of feeding on host body-fluids and after 24 h feeding/24 h starvation. The cells were found to be complex and contain an organelle component that allows solute-transport and extensive lipid synthesis. A limited cytochemical analysis involving the lysosomal marker enzyme-acid phosphatase--and the respiratory enzyme--cytochrome oxidase was carried out.", "contents": "The ultrastructure of the mid-gut cells of Nasonia vitripennis (Walker) (Hymenoptera, Pteromalidae). The ultrastructure of the mid-gut cells of female Nasonia vitripennis is described. The mid-gut consists of a uniform, single-cell epithelium. The cells of different gut regions were analysed using morphometric techniques in order to determine any differences in the components. The structure of the cells is described in the unfed animal, and after varying periods of feeding on host body-fluids. Tissues were sampled after 12 h and 24 h of feeding on host body-fluids and after 24 h feeding/24 h starvation. The cells were found to be complex and contain an organelle component that allows solute-transport and extensive lipid synthesis. A limited cytochemical analysis involving the lysosomal marker enzyme-acid phosphatase--and the respiratory enzyme--cytochrome oxidase was carried out."}
{"id": "PMID:189931", "title": "Lipids in the proximal convoluted tubule of the cat kidney and the reabsorption of cholesterol.", "content": "Lipid deposits in the cat kidney are mainly located in the epithelium of the proximal tubuli contorti, particularly in the pars contorta. As the amount of fatty acids in the blood of renal arteries is higher than in renal veins, the lipid inclusions are likely to be formed in the proximal convoluted tubule. Whether fat occurring in the urine has been released from the nephron epithelium and the mode of this release remains obscure. The structural equivalent of lipid extrusion into the tubules has not been observed. Components of the tubular lipids include triglycerides, phosphoglycerides and cholesterol. The results of the digitonin-cholesterol reaction favour the assumption that cholesterol is eliminated in the glomeruli and pinocytotically reabsorbed by the brush border cells, this process possibly serving recycling of this compound. The dilated basal labyrinth and intercellular space contain perpendicularly oriented lipid accumulations that reach the basal lamina. The ultrastructure of the lipid storing cells of pars contorta reacting positively for phosphoglyceride and cholesterol is characterised mainly by bodies with marginal plates. As far as can be judged from their morphology, these bodies are interpreted as large peroxisomes. A special feature of the pars recta are dumbbell shaped bodies and elongated or cup-like mitochondria concentrically surrounding cytoplasmic areas, as well as a well-developed smooth ER. In what way the organelles of the brush border cells are involved in catabolic and anabolic processes as far as renal lipid metabolism is concerned remains to be answered.", "contents": "Lipids in the proximal convoluted tubule of the cat kidney and the reabsorption of cholesterol. Lipid deposits in the cat kidney are mainly located in the epithelium of the proximal tubuli contorti, particularly in the pars contorta. As the amount of fatty acids in the blood of renal arteries is higher than in renal veins, the lipid inclusions are likely to be formed in the proximal convoluted tubule. Whether fat occurring in the urine has been released from the nephron epithelium and the mode of this release remains obscure. The structural equivalent of lipid extrusion into the tubules has not been observed. Components of the tubular lipids include triglycerides, phosphoglycerides and cholesterol. The results of the digitonin-cholesterol reaction favour the assumption that cholesterol is eliminated in the glomeruli and pinocytotically reabsorbed by the brush border cells, this process possibly serving recycling of this compound. The dilated basal labyrinth and intercellular space contain perpendicularly oriented lipid accumulations that reach the basal lamina. The ultrastructure of the lipid storing cells of pars contorta reacting positively for phosphoglyceride and cholesterol is characterised mainly by bodies with marginal plates. As far as can be judged from their morphology, these bodies are interpreted as large peroxisomes. A special feature of the pars recta are dumbbell shaped bodies and elongated or cup-like mitochondria concentrically surrounding cytoplasmic areas, as well as a well-developed smooth ER. In what way the organelles of the brush border cells are involved in catabolic and anabolic processes as far as renal lipid metabolism is concerned remains to be answered."}
{"id": "PMID:189932", "title": "Infection of cultured rat hepatoma cells by mouse mammary tumor virus.", "content": "A continuous line of buffalo rat hepatoma (HTC) cells has been successfully infected with mouse mammary tumor virus (MMTV) produced by the GR mammary tumor cell line. Uniform infection required initial exposure of the HTC cells to greater than 10(5) MMTV particles per cell. The resultant chronically infected cell population was found to have stably acquired 20-30 copies of MMTV DNA. The infected cells contain viral RNA and express viral antigens; however, very few MMTV particles are released into the culture medium. In spite of the biochemical evidence for infection, we have not detected any alterations in the morphology or growth properties of the infected HTC cells. As is the case in mammary tumor cells, the intracellular concentration of viral RNA is strongly stimulated (50-150 fold) by the synthetic glucorcorticoid, dexamethasone. Thus it appears that the mechanisms by which glucorticoids regulate MMTV gene expression in mouse cells are maintained when this virus infects nonmurine cells.", "contents": "Infection of cultured rat hepatoma cells by mouse mammary tumor virus. A continuous line of buffalo rat hepatoma (HTC) cells has been successfully infected with mouse mammary tumor virus (MMTV) produced by the GR mammary tumor cell line. Uniform infection required initial exposure of the HTC cells to greater than 10(5) MMTV particles per cell. The resultant chronically infected cell population was found to have stably acquired 20-30 copies of MMTV DNA. The infected cells contain viral RNA and express viral antigens; however, very few MMTV particles are released into the culture medium. In spite of the biochemical evidence for infection, we have not detected any alterations in the morphology or growth properties of the infected HTC cells. As is the case in mammary tumor cells, the intracellular concentration of viral RNA is strongly stimulated (50-150 fold) by the synthetic glucorcorticoid, dexamethasone. Thus it appears that the mechanisms by which glucorticoids regulate MMTV gene expression in mouse cells are maintained when this virus infects nonmurine cells."}
{"id": "PMID:189933", "title": "Mouse mammary tumor virus DNA in infected rat cells: characterization of unintegrated forms.", "content": "Mouse mammary tumor virus (MMTV) DNA in chronically infected rat hepatoma cells is maintained in both the integrated and unintegrated state. Fractionation of DNA by the procedure of Hirt (1967) as well as by sedimentation through alkaline sucrose suggests that about two thirds of the viral DNA is associated with high molecular weight cell DNA. The remainder of the viral DNA is unintegrated and is present primarily as linear or open circular duplexes consisting of a genome-length strand complementary to the viral RNA (\"minus\" strand) and \"plus\" strands of subgenomic length. Approximately 20% of the unintegrated MMTV DNA is present as double-stranded, covently closed circles (form I) with a molecular weight of 6 X 10(6) daltons. Form I viral DNA is found primarily in the nucleus, whereas the open forms are both nuclear and cytoplasmic.", "contents": "Mouse mammary tumor virus DNA in infected rat cells: characterization of unintegrated forms. Mouse mammary tumor virus (MMTV) DNA in chronically infected rat hepatoma cells is maintained in both the integrated and unintegrated state. Fractionation of DNA by the procedure of Hirt (1967) as well as by sedimentation through alkaline sucrose suggests that about two thirds of the viral DNA is associated with high molecular weight cell DNA. The remainder of the viral DNA is unintegrated and is present primarily as linear or open circular duplexes consisting of a genome-length strand complementary to the viral RNA (\"minus\" strand) and \"plus\" strands of subgenomic length. Approximately 20% of the unintegrated MMTV DNA is present as double-stranded, covently closed circles (form I) with a molecular weight of 6 X 10(6) daltons. Form I viral DNA is found primarily in the nucleus, whereas the open forms are both nuclear and cytoplasmic."}
{"id": "PMID:189934", "title": "Decreased adherence to the substrate in Rous sarcoma virus-transformed chicken embryo fibroblasts.", "content": "Cell-substrate adherence in cultures of chicken embryo fibroblasts was examined by determining the number of cells which could be detached from the culture dish by a stream of medium. Transformed cells were significantly less adherent than their normal counterparts. In cultures infected with a mutant of Rous sarcoma virus which is temperature-conditional for transformation, adherence changed promptly following a temperature shift. This change did not require progression through the cell cycle. The transformation-specific decrease in adherence required new protein synthesis, but the restoration of adherence which occurred following a shift to the restrictive temperature could occur in the absence of new protein synthesis. Inhibitor experiments suggested the importance of microfilaments and perhaps microtubules in the changes in detachability. In addition, there was a positive correlation between levels of surface LETS protein and cell substrate adherence following a temperature shift, although it seems probable that the bulk of the surface LETS is neither necessary nor sufficient for maintenance of normal cell substrate adherence.", "contents": "Decreased adherence to the substrate in Rous sarcoma virus-transformed chicken embryo fibroblasts. Cell-substrate adherence in cultures of chicken embryo fibroblasts was examined by determining the number of cells which could be detached from the culture dish by a stream of medium. Transformed cells were significantly less adherent than their normal counterparts. In cultures infected with a mutant of Rous sarcoma virus which is temperature-conditional for transformation, adherence changed promptly following a temperature shift. This change did not require progression through the cell cycle. The transformation-specific decrease in adherence required new protein synthesis, but the restoration of adherence which occurred following a shift to the restrictive temperature could occur in the absence of new protein synthesis. Inhibitor experiments suggested the importance of microfilaments and perhaps microtubules in the changes in detachability. In addition, there was a positive correlation between levels of surface LETS protein and cell substrate adherence following a temperature shift, although it seems probable that the bulk of the surface LETS is neither necessary nor sufficient for maintenance of normal cell substrate adherence."}
{"id": "PMID:189935", "title": "The genome-associated, specific RNA binding proteins of avian and mammalian type C viruses.", "content": "A structural protein purified from the Rous sarcoma virus (RSV) can specificially bind in vitro to purified avian, but not mammalian, type C viral RNA. Following ultraviolet irradiation of viral particles under conditions which stabilize the polyploid 70S viral RNA, the same polypeptide can be directly purified from the RSV genome. Based on its electrophoretic mobility in polyacrylamide gels containing sodium dodecylsulfate, the RNA binding protein has been identified as the major phosphoprotein (p19) of avian type C viruses. Similar experiments show that the major phosphoproteins of mammalian type C viruses (p12 for murine viruses and p16 for endogenous primate viruses) are also the specific RNA binding proteins and, similarly, are found closely associated with the 70S RNA genomes in the intact viral particles.", "contents": "The genome-associated, specific RNA binding proteins of avian and mammalian type C viruses. A structural protein purified from the Rous sarcoma virus (RSV) can specificially bind in vitro to purified avian, but not mammalian, type C viral RNA. Following ultraviolet irradiation of viral particles under conditions which stabilize the polyploid 70S viral RNA, the same polypeptide can be directly purified from the RSV genome. Based on its electrophoretic mobility in polyacrylamide gels containing sodium dodecylsulfate, the RNA binding protein has been identified as the major phosphoprotein (p19) of avian type C viruses. Similar experiments show that the major phosphoproteins of mammalian type C viruses (p12 for murine viruses and p16 for endogenous primate viruses) are also the specific RNA binding proteins and, similarly, are found closely associated with the 70S RNA genomes in the intact viral particles."}
{"id": "PMID:189936", "title": "Assembly of SV40 chromatin in a cell-free system from Xenopus eggs.", "content": "A cell-free system is described which assembles chromatin from purified DNA in 1 hr under physiological incubation conditions. It consists of a 145,000 x g (maximum) supernatant fraction from eggs of Xenopus laevis. It converts SV40 DNA to a nucleoprotein which co-sediments with naturally occurring SV40 chromatin and which can be cleaved by micrococcal nuclease to a highly ordered pattern of DNA fragments resembling those from digestion of liver chromatin. It inserts superhelical turns into relaxed, covalently closed DNA. The assembly process is not cooperative. Under limiting conditions, each DNA molecule becomes partially assembled. Assembly does not require replication of the DNA or protein synthesis, but occurs from a stored histone pool of at least 40 ng per egg. Under conditions of DNA excess, assembly becomes dependent upon the amount of exogenous histones added to the incubation. Apart from histones and a nicking-closing activity, chromatin assembly requires an additonal thermolabile factor which is present in the egg supernatant.", "contents": "Assembly of SV40 chromatin in a cell-free system from Xenopus eggs. A cell-free system is described which assembles chromatin from purified DNA in 1 hr under physiological incubation conditions. It consists of a 145,000 x g (maximum) supernatant fraction from eggs of Xenopus laevis. It converts SV40 DNA to a nucleoprotein which co-sediments with naturally occurring SV40 chromatin and which can be cleaved by micrococcal nuclease to a highly ordered pattern of DNA fragments resembling those from digestion of liver chromatin. It inserts superhelical turns into relaxed, covalently closed DNA. The assembly process is not cooperative. Under limiting conditions, each DNA molecule becomes partially assembled. Assembly does not require replication of the DNA or protein synthesis, but occurs from a stored histone pool of at least 40 ng per egg. Under conditions of DNA excess, assembly becomes dependent upon the amount of exogenous histones added to the incubation. Apart from histones and a nicking-closing activity, chromatin assembly requires an additonal thermolabile factor which is present in the egg supernatant."}
{"id": "PMID:189937", "title": "Teratocarcinoma differentiation: plasminogen activator activity associated with embryoid body formation.", "content": "Changes in plasminogen activator activity have been examined as a clonal line of mouse embryonal carcinoma cells aggregate and differentiate to form cystic embryoid bodies in vitro. Within the first 10 days of study, the pluripotent embryonal carcinoma cells aggregate; a layer of endodermal cells appears on the outside of the aggregate forming an embryoid body; a basement membrane forms between the outer layer of endodermal cells and the internal cells; a cyst forms within the embryoid body; and the internal cells assume a columnar appearance along the inner portion of the basement membrane. After the formation of the endodermal layer, there is a rise in intracellular plasminogen activator activity. This rise continues for up to 25 days in culture, providing that the three-dimensional integrity of the embryoid bodies is maintained by culturing them on bacterial petri dishes. Selective removal of the outer endodermal layer of cells reduces the plasminogen activatory activity of the resulting embryoid body cores. Intracellular and secreted plasminogen activator activity of simple embryoid bodies composed of only two cell types can be increased by culturing the embryoid bodies in dbcAMP, theophylline, or cholera toxin. These results suggest that the embryoid body endodermal cells are the source of a cAMP-inducible plasminogen activator activity.", "contents": "Teratocarcinoma differentiation: plasminogen activator activity associated with embryoid body formation. Changes in plasminogen activator activity have been examined as a clonal line of mouse embryonal carcinoma cells aggregate and differentiate to form cystic embryoid bodies in vitro. Within the first 10 days of study, the pluripotent embryonal carcinoma cells aggregate; a layer of endodermal cells appears on the outside of the aggregate forming an embryoid body; a basement membrane forms between the outer layer of endodermal cells and the internal cells; a cyst forms within the embryoid body; and the internal cells assume a columnar appearance along the inner portion of the basement membrane. After the formation of the endodermal layer, there is a rise in intracellular plasminogen activator activity. This rise continues for up to 25 days in culture, providing that the three-dimensional integrity of the embryoid bodies is maintained by culturing them on bacterial petri dishes. Selective removal of the outer endodermal layer of cells reduces the plasminogen activatory activity of the resulting embryoid body cores. Intracellular and secreted plasminogen activator activity of simple embryoid bodies composed of only two cell types can be increased by culturing the embryoid bodies in dbcAMP, theophylline, or cholera toxin. These results suggest that the embryoid body endodermal cells are the source of a cAMP-inducible plasminogen activator activity."}
{"id": "PMID:189938", "title": "Differential genetic susceptibility of cultured human skin fibroblasts to transformation by Kirsten murine sarcoma virus.", "content": "Hereditary adenomatosis of the colon and rectum (ACR), an autosomal dominant trait, is associated with a predisposition to neoplasia. The present study describes the differential genetic susceptibility of cultured human skin fibroblasts to transformation by Kirsten murine sarcoma virus. Primary cutaneous outgrowths were derived from normal appearing subepidermal biopsies of ACR phenotypes and appropriate controls. Exponentially growing cell cultures from ACR subjects and a portion of the clinically asymptomatic ACR progeny subjected to the viral probe were 100-1000 fold more susceptible to transformation than were normal skin fibroblast cultures. The virally transformed human skin fibroblasts showed a loss of anchorage dependency in carboxymethylcellulose suspension and formed tumors in athymic mice. The results suggest that skin fibroblasts obtained from individuals gine sarcoma virus.", "contents": "Differential genetic susceptibility of cultured human skin fibroblasts to transformation by Kirsten murine sarcoma virus. Hereditary adenomatosis of the colon and rectum (ACR), an autosomal dominant trait, is associated with a predisposition to neoplasia. The present study describes the differential genetic susceptibility of cultured human skin fibroblasts to transformation by Kirsten murine sarcoma virus. Primary cutaneous outgrowths were derived from normal appearing subepidermal biopsies of ACR phenotypes and appropriate controls. Exponentially growing cell cultures from ACR subjects and a portion of the clinically asymptomatic ACR progeny subjected to the viral probe were 100-1000 fold more susceptible to transformation than were normal skin fibroblast cultures. The virally transformed human skin fibroblasts showed a loss of anchorage dependency in carboxymethylcellulose suspension and formed tumors in athymic mice. The results suggest that skin fibroblasts obtained from individuals gine sarcoma virus."}
{"id": "PMID:189939", "title": "cAMP,-induced changes in cAMP-binding sites on D; discoideum amebae.", "content": "Cell surface levels of 3H-cAMP binding to Dictyostelium discoideum amebae are dramatically reduced when cells are preincubated with cAMP. This decrease in 3H-cAMP binding is shown to reflect a loss in the number of binding sites and not in any significant change in their affinity constants(s). cAMP-mediated loss of its binding sites requires the continued presence of the cyclic nucleotide and does not depend upon protein synthesis. Reapparition of sites, which occurs when cAMP is eliminated from the media, also does not depend upon protein synthesis. Experiments using metabolic inhibitors and heat-killed cells suggest that the loss of binding sites is a direct consequence of the formation of cAMP-binding protein complexes.", "contents": "cAMP,-induced changes in cAMP-binding sites on D; discoideum amebae. Cell surface levels of 3H-cAMP binding to Dictyostelium discoideum amebae are dramatically reduced when cells are preincubated with cAMP. This decrease in 3H-cAMP binding is shown to reflect a loss in the number of binding sites and not in any significant change in their affinity constants(s). cAMP-mediated loss of its binding sites requires the continued presence of the cyclic nucleotide and does not depend upon protein synthesis. Reapparition of sites, which occurs when cAMP is eliminated from the media, also does not depend upon protein synthesis. Experiments using metabolic inhibitors and heat-killed cells suggest that the loss of binding sites is a direct consequence of the formation of cAMP-binding protein complexes."}
{"id": "PMID:189940", "title": "Analysis of a mutant strain of human fibroblasts with a defect in the internalization of receptor-bound low density lipoprotein.", "content": "A new type of mutation that affects a discrete step in the process of adsorptive endocytosis has been identified in one of 22 strains of fibroblasts derived from subjects with the clinical phenotype of homozygous familial hypercholesterolemia (FH). In this unique mutant strain (derived from subject J.D.), the cell surface receptor for plasma low density lipoprotein (LDL) was able to bind 125I-labeled LDL normally, but internalization of the receptor-bound lipoprotein failed to occur. Thus the defect in this strain differed from the defects found in the fibroblasts from the other 21 FH homozygote strains in which the binding of 125I-LDL to the receptor was either absent (receptor-negative) or markedly reduced (receptor-defective). The LDL receptor in the J.D. cells exhibited first, normal kinetics of high affinity binding at 4 degrees C and 37 degrees C; second, normal specificity (affinity for LDL more than 200 fold greater than for HDL); third, normal susceptibility to feed-back suppression by 25-hydroxycholesterol plus cholesterol; and fourth, a normal rate of turnover when the cells were treated with cycloheximide. Despite its normal ability to bind 125I-LDL, the LDL receptor in the J.D. cells failed to transport its LDL into the cell, and degradation of the lipoprotein in cellular lysosomes therefore did not occur. As a result, the lipoprotein did not suppress 3-hydroxy-3-methylglutaryl coenzyme A reductase activity; nor did it activate cholesteryl ester formation. A phenocopy of the internalization defect in the J.D. cells could be created by incubation of normal fibroblasts with N-ethyl maleimide, an agent that did not affect 125I-LDL binding to the receptor but blocked its subsequent internalization by the cell. The current data indicate that at least two gene products are necessary for the adsorptive endocytosis of LDL: one that is required for the binding of the lipoprotein, and one that promotes the internalization of the receptor-bound ligand.", "contents": "Analysis of a mutant strain of human fibroblasts with a defect in the internalization of receptor-bound low density lipoprotein. A new type of mutation that affects a discrete step in the process of adsorptive endocytosis has been identified in one of 22 strains of fibroblasts derived from subjects with the clinical phenotype of homozygous familial hypercholesterolemia (FH). In this unique mutant strain (derived from subject J.D.), the cell surface receptor for plasma low density lipoprotein (LDL) was able to bind 125I-labeled LDL normally, but internalization of the receptor-bound lipoprotein failed to occur. Thus the defect in this strain differed from the defects found in the fibroblasts from the other 21 FH homozygote strains in which the binding of 125I-LDL to the receptor was either absent (receptor-negative) or markedly reduced (receptor-defective). The LDL receptor in the J.D. cells exhibited first, normal kinetics of high affinity binding at 4 degrees C and 37 degrees C; second, normal specificity (affinity for LDL more than 200 fold greater than for HDL); third, normal susceptibility to feed-back suppression by 25-hydroxycholesterol plus cholesterol; and fourth, a normal rate of turnover when the cells were treated with cycloheximide. Despite its normal ability to bind 125I-LDL, the LDL receptor in the J.D. cells failed to transport its LDL into the cell, and degradation of the lipoprotein in cellular lysosomes therefore did not occur. As a result, the lipoprotein did not suppress 3-hydroxy-3-methylglutaryl coenzyme A reductase activity; nor did it activate cholesteryl ester formation. A phenocopy of the internalization defect in the J.D. cells could be created by incubation of normal fibroblasts with N-ethyl maleimide, an agent that did not affect 125I-LDL binding to the receptor but blocked its subsequent internalization by the cell. The current data indicate that at least two gene products are necessary for the adsorptive endocytosis of LDL: one that is required for the binding of the lipoprotein, and one that promotes the internalization of the receptor-bound ligand."}
{"id": "PMID:189941", "title": "Transformation of cultured human vascular endothelium by SV40 DNA.", "content": "Primary cultures of human umbilical vein endothelial cells (HEC) developed extensive cytopathic changes and necrosis after high multiplicity infection with wild-type SV40 virus. Using the calcium co-precipitation technique, stable transformation was obtained with purified preparations of intact circular SV40 DNA and restriction endonuclease-derived linear DNA fragments containing the entire early gene region. Smooth muscle cells, isolated from the same blood vessels, showed neither cytopathic effects nor transformation after similar treatment with SV40 virus or DNA. The HEC cultures transformed by SV40 (SVHEC) expressed SV40-specific T (tumor) and Tr (transplantation) antigens, but not V (viral capsid) antigen. No evidence of infectious virus production was found upon co-cultivation with the CV-1 line of monkey kidney cells. Transformation resulted in markedly increased growth potential, loss of anchorage dependence and topoinhibition of growth, and a reduced serum requirement. Prolonged subcultivation was accompanied by chromosomal abnormalities and eventual \"crisis\". Transformed cells did not exhibit endothelial-specific organelles (Weibel-Palade bodies) or factor VIII antigen, but angiotensin-converting enzyme occasionally was detectable in SVHEC cultures. SV40-transformed human vascular endothelium, a nonfibroblast diploid cell type, may be useful in studies of oncogenesis and control of the differentiated state.", "contents": "Transformation of cultured human vascular endothelium by SV40 DNA. Primary cultures of human umbilical vein endothelial cells (HEC) developed extensive cytopathic changes and necrosis after high multiplicity infection with wild-type SV40 virus. Using the calcium co-precipitation technique, stable transformation was obtained with purified preparations of intact circular SV40 DNA and restriction endonuclease-derived linear DNA fragments containing the entire early gene region. Smooth muscle cells, isolated from the same blood vessels, showed neither cytopathic effects nor transformation after similar treatment with SV40 virus or DNA. The HEC cultures transformed by SV40 (SVHEC) expressed SV40-specific T (tumor) and Tr (transplantation) antigens, but not V (viral capsid) antigen. No evidence of infectious virus production was found upon co-cultivation with the CV-1 line of monkey kidney cells. Transformation resulted in markedly increased growth potential, loss of anchorage dependence and topoinhibition of growth, and a reduced serum requirement. Prolonged subcultivation was accompanied by chromosomal abnormalities and eventual \"crisis\". Transformed cells did not exhibit endothelial-specific organelles (Weibel-Palade bodies) or factor VIII antigen, but angiotensin-converting enzyme occasionally was detectable in SVHEC cultures. SV40-transformed human vascular endothelium, a nonfibroblast diploid cell type, may be useful in studies of oncogenesis and control of the differentiated state."}
{"id": "PMID:189942", "title": "Construction of hybrid viruses containing SV40 and lambda phage DNA segments and their propagation in cultured monkey cells.", "content": "This paper describes the successful construction and propagation of a transducing animal virus. A segment of DNA approximately 2 kilobases (kb) in length was removed from the late region of the SV40 genome by sequential cleavages with Hpa II and Bam HI endonucleases (at 0.735 and 0.13, respectively, on the SV40 DNA map). A segment of about 1.5 kb of lambda phage containing ORI (the origin of lambda DNA replication), the two structural genes CII and cro, and four transcriptional promoters, was inserted into the late region of SV40 by the poly(dA:dT) joining procedure. The resulting hybrid DNAs were cloned and propagated as virions in CV-1 monkey kidney cells by mixed infections at 41 degrees C with tsA58, an early mutant of SV40. The location, size, and orientation of the inserted lambda DNA segment was verified by restriction endonuclease digestions and by heteroduplex analysis. Clones with each of the two possible orientations of the lambda DNA segment were isolated. CV-1 cells infected with lambda-SV40 hybrid virus contain little or no lambda-specific RNA or proteins, even though the hybrid virus replicates nearly as well as the helper virus.", "contents": "Construction of hybrid viruses containing SV40 and lambda phage DNA segments and their propagation in cultured monkey cells. This paper describes the successful construction and propagation of a transducing animal virus. A segment of DNA approximately 2 kilobases (kb) in length was removed from the late region of the SV40 genome by sequential cleavages with Hpa II and Bam HI endonucleases (at 0.735 and 0.13, respectively, on the SV40 DNA map). A segment of about 1.5 kb of lambda phage containing ORI (the origin of lambda DNA replication), the two structural genes CII and cro, and four transcriptional promoters, was inserted into the late region of SV40 by the poly(dA:dT) joining procedure. The resulting hybrid DNAs were cloned and propagated as virions in CV-1 monkey kidney cells by mixed infections at 41 degrees C with tsA58, an early mutant of SV40. The location, size, and orientation of the inserted lambda DNA segment was verified by restriction endonuclease digestions and by heteroduplex analysis. Clones with each of the two possible orientations of the lambda DNA segment were isolated. CV-1 cells infected with lambda-SV40 hybrid virus contain little or no lambda-specific RNA or proteins, even though the hybrid virus replicates nearly as well as the helper virus."}
{"id": "PMID:189943", "title": "Nucleotide sequences at the 5'termini of rabbit alpha and beta globin mRNA.", "content": "The nucleotide sequences at the 5' termini of rabbit alpha and beta globin mRNAs have been determined. Periodate oxidation of globin mRNA followed by reduction with 3H-sodium borohydride and subsequent analysis of the 3H-labeled mRNA reveals the presence of the \"cap\" structure m7G5'ppp- blocking the 5' terminus. After periodate oxidation, beta elimination, and phosphomonoesterase treatment to remove the m7G5'ppp- \"cap,\" the 5' end of globin mRNA was labeled with 32P using gamma-32P-ATP and T4 polynucleotide kinase. The 5'-32P-labeled alpha and beta globin mRNAs were then resolved from each other by polyacrylamide gel electrophoresis under denaturing conditions and sequenced separately. The 5' terminal nucleotide sequences determined are: alpha--m7G5'ppp5m6AmC(m)ACUUCUGG- BETA--M7G5'ppp5m6AmC(m) ACUUGCUUUUGACACAA Besides the m7G \"cap\" structure, the two sequences are identical for the first six nucleotides and then diverge. No initiator codon is present within the first ten nucleotides from the 5' end of the alpha globin mRNA, and the first nineteen nucleotides from the 5' end of beta globin mRNA.", "contents": "Nucleotide sequences at the 5'termini of rabbit alpha and beta globin mRNA. The nucleotide sequences at the 5' termini of rabbit alpha and beta globin mRNAs have been determined. Periodate oxidation of globin mRNA followed by reduction with 3H-sodium borohydride and subsequent analysis of the 3H-labeled mRNA reveals the presence of the \"cap\" structure m7G5'ppp- blocking the 5' terminus. After periodate oxidation, beta elimination, and phosphomonoesterase treatment to remove the m7G5'ppp- \"cap,\" the 5' end of globin mRNA was labeled with 32P using gamma-32P-ATP and T4 polynucleotide kinase. The 5'-32P-labeled alpha and beta globin mRNAs were then resolved from each other by polyacrylamide gel electrophoresis under denaturing conditions and sequenced separately. The 5' terminal nucleotide sequences determined are: alpha--m7G5'ppp5m6AmC(m)ACUUCUGG- BETA--M7G5'ppp5m6AmC(m) ACUUGCUUUUGACACAA Besides the m7G \"cap\" structure, the two sequences are identical for the first six nucleotides and then diverge. No initiator codon is present within the first ten nucleotides from the 5' end of the alpha globin mRNA, and the first nineteen nucleotides from the 5' end of beta globin mRNA."}
{"id": "PMID:189945", "title": "Interaction of Pt(II) complexes with DNAs from various sources. A circular dichroism study.", "content": "The interaction of cis- and trans-Pt(NH3)2Cl2 with DNAs of different base composition was studied by means of circular dichroism (CD) spectroscopy. The spectra obtained indicated a partial transformation of the secondary structure of DNA (B- less than C transition) with an increased helix winding. Subtle differences were noted between the two isomers, possibly related to changes in base orientation due to the different molecular geometries of the P+(II) complexes.", "contents": "Interaction of Pt(II) complexes with DNAs from various sources. A circular dichroism study. The interaction of cis- and trans-Pt(NH3)2Cl2 with DNAs of different base composition was studied by means of circular dichroism (CD) spectroscopy. The spectra obtained indicated a partial transformation of the secondary structure of DNA (B- less than C transition) with an increased helix winding. Subtle differences were noted between the two isomers, possibly related to changes in base orientation due to the different molecular geometries of the P+(II) complexes."}
{"id": "PMID:189951", "title": "[Lipase activity of anaerobic bacteria on glycerol-tributyrate determined by gas-liquid chromatography].", "content": "Anaerobic bacteria are classified among other criteria by the presence or absence of phospholipase and lipase. The liquid gas chromatographic method detects with great sensibility the lipasic activity of the anaerobic bacteria. A liidolytic action has been demonstrated in Cl. perfringens.", "contents": "[Lipase activity of anaerobic bacteria on glycerol-tributyrate determined by gas-liquid chromatography]. Anaerobic bacteria are classified among other criteria by the presence or absence of phospholipase and lipase. The liquid gas chromatographic method detects with great sensibility the lipasic activity of the anaerobic bacteria. A liidolytic action has been demonstrated in Cl. perfringens."}
{"id": "PMID:189949", "title": "[Development of the Bandama Valley. Sanitary and social problems].", "content": "As with all water resources development projects in countries with hot climate, the man-made lake of Kossou in Ivory Coast presents social and sanitary problems. Although the resettlement and the economic recuperation of the inhabitants are well on the way, the health hazards and especially that of the generalization of schistosomiasis calls for an urgent solution. Though well planed in advance, the creation of this man-made lake, illustrates the necessity at the very beginning of a project that will distrub all the ecology of a region, to establish the total disadvantages and health hazards incurved by the people who live there. To the cost of a project should be added that of measures that would contribute to the reduction of these risks before it is too late.", "contents": "[Development of the Bandama Valley. Sanitary and social problems]. As with all water resources development projects in countries with hot climate, the man-made lake of Kossou in Ivory Coast presents social and sanitary problems. Although the resettlement and the economic recuperation of the inhabitants are well on the way, the health hazards and especially that of the generalization of schistosomiasis calls for an urgent solution. Though well planed in advance, the creation of this man-made lake, illustrates the necessity at the very beginning of a project that will distrub all the ecology of a region, to establish the total disadvantages and health hazards incurved by the people who live there. To the cost of a project should be added that of measures that would contribute to the reduction of these risks before it is too late."}
{"id": "PMID:189952", "title": "Comparative effects of physical training and diet in normalizing serum lipids in men with Type IV hyperlipoproteinemia.", "content": "The effect of milk physical training (PT) (group A), Type IV hyperlipoproteinemia (HLP) diet (group B), and PT plus Type IV HLP diet on serum lipids (group C) in 46 men with Type IV HLP was studied. Significant reductions in mean triglyceride (TG) levels from 163, 229, 196, to 136, 145, 116 mg/100 ml serum were found for groups A, B, and C, respectively. Following six weeks of intervention, cholesterol levels also dropped for all groups with the greatest reductions occurring in groups B and C. Minimal weight losses were found for all groups while groups A and C displayed significant reductions in body fatness, but both of these changes appeared independent of lipid reductions. It was concluded that either mild PT or HLP diet or both are effective means of lowering TG levels in Type IV HLP individuals. Furthermore, it appears that patients need to participate regularly in formal programs in order to maintain adherence to these interventions.", "contents": "Comparative effects of physical training and diet in normalizing serum lipids in men with Type IV hyperlipoproteinemia. The effect of milk physical training (PT) (group A), Type IV hyperlipoproteinemia (HLP) diet (group B), and PT plus Type IV HLP diet on serum lipids (group C) in 46 men with Type IV HLP was studied. Significant reductions in mean triglyceride (TG) levels from 163, 229, 196, to 136, 145, 116 mg/100 ml serum were found for groups A, B, and C, respectively. Following six weeks of intervention, cholesterol levels also dropped for all groups with the greatest reductions occurring in groups B and C. Minimal weight losses were found for all groups while groups A and C displayed significant reductions in body fatness, but both of these changes appeared independent of lipid reductions. It was concluded that either mild PT or HLP diet or both are effective means of lowering TG levels in Type IV HLP individuals. Furthermore, it appears that patients need to participate regularly in formal programs in order to maintain adherence to these interventions."}
{"id": "PMID:189953", "title": "Hydrolysis of steroid glucuronides with beta-glucuronidase preparations from bovine liver, Helix pomatia, and E. coli.", "content": "We determined the enzymic activity of beta-glucuronidase preparations from bovine liver, Helix pomatia, and Escherischia coli with steroid glucuronides and nonsteroid glucuronides as substrates. We also studied the effect of Na2SO4 on the enzymic hydrolysis of several substrates with the three preparations of beta-glucuronidase. Na2SO4 increases the rate of hydrolysis of all substrates with beta-glucuronidase from bovine liver. Hydrolysis of a steroid glucoronide with beta-glucuronidase from Helix pomatia and E. coli is inhibited by Na2SO4. None of the three enzyme preparations gives complete hydrolysis of urinary steroid conjugates, because urine contains inhibitors, which can be removed by absorption chromatography of the urine on a column of neutral polystyrene resin Amberlite XAD-2. But when Amberlite XAD-2 is not used, hydrolysis of urinary glucuronides of androsterone, etiocholanolone, pregnanediol, estriol, and 17-hydroxycorticosteroids proves that, given an incubation time of 24 h, the beta-glucuronidase preparation from bovine liver, in the presence of Na2SO4, is suited for determining all of the above steroids except esriol; the preparation from Helix pomatia is good for determining estriol and 17-hydroxycorticosteroids; the preparation from E. coli is good for determining androsterone, 17-hydroxycorticosteroids, and especially estriol, the glucuronide, of which is maximally hydrolyzed in 2 h.", "contents": "Hydrolysis of steroid glucuronides with beta-glucuronidase preparations from bovine liver, Helix pomatia, and E. coli. We determined the enzymic activity of beta-glucuronidase preparations from bovine liver, Helix pomatia, and Escherischia coli with steroid glucuronides and nonsteroid glucuronides as substrates. We also studied the effect of Na2SO4 on the enzymic hydrolysis of several substrates with the three preparations of beta-glucuronidase. Na2SO4 increases the rate of hydrolysis of all substrates with beta-glucuronidase from bovine liver. Hydrolysis of a steroid glucoronide with beta-glucuronidase from Helix pomatia and E. coli is inhibited by Na2SO4. None of the three enzyme preparations gives complete hydrolysis of urinary steroid conjugates, because urine contains inhibitors, which can be removed by absorption chromatography of the urine on a column of neutral polystyrene resin Amberlite XAD-2. But when Amberlite XAD-2 is not used, hydrolysis of urinary glucuronides of androsterone, etiocholanolone, pregnanediol, estriol, and 17-hydroxycorticosteroids proves that, given an incubation time of 24 h, the beta-glucuronidase preparation from bovine liver, in the presence of Na2SO4, is suited for determining all of the above steroids except esriol; the preparation from Helix pomatia is good for determining estriol and 17-hydroxycorticosteroids; the preparation from E. coli is good for determining androsterone, 17-hydroxycorticosteroids, and especially estriol, the glucuronide, of which is maximally hydrolyzed in 2 h."}
{"id": "PMID:189954", "title": "Beta-lipoprotein cholesterol quantitation with polycations.", "content": "We compared direct determination of beta-lipoprotein cholesterol after selective extraction of very-low-density and high-density lipoproteins from serum with poly(ethyleneimine) and a cation-exchange resin with the classical quantitation after lipoprotein fractionation with the ultracentrifuge. At beta-lipoprotein cholesterol concentrations between 1.50 and 5.00 g/liter the correlation is linear (r = 0.95). The precision for the extraction procedure is as good (CV 2.4-2.8%) as for the quantitation by ultracentrifugation (CV 3.2-6.0%). From solutions of isolated lipoproteins, very-low-density lipoproteins are 93% extracted and high-density lipoproteins 60%, but low-density-lipoproteins only 5%. The molecular mechanism of the extraction is supposed to be due to both hydrophobic interaction of long-chain fatty acid residues and ionic interaction of phospholipids located at the surface of very low-density and high-density lipoproteins and the lipophilic polycation.", "contents": "Beta-lipoprotein cholesterol quantitation with polycations. We compared direct determination of beta-lipoprotein cholesterol after selective extraction of very-low-density and high-density lipoproteins from serum with poly(ethyleneimine) and a cation-exchange resin with the classical quantitation after lipoprotein fractionation with the ultracentrifuge. At beta-lipoprotein cholesterol concentrations between 1.50 and 5.00 g/liter the correlation is linear (r = 0.95). The precision for the extraction procedure is as good (CV 2.4-2.8%) as for the quantitation by ultracentrifugation (CV 3.2-6.0%). From solutions of isolated lipoproteins, very-low-density lipoproteins are 93% extracted and high-density lipoproteins 60%, but low-density-lipoproteins only 5%. The molecular mechanism of the extraction is supposed to be due to both hydrophobic interaction of long-chain fatty acid residues and ionic interaction of phospholipids located at the surface of very low-density and high-density lipoproteins and the lipophilic polycation."}
{"id": "PMID:189955", "title": "Radioimmunoassay for adenosine 3', 5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate in human blood, urine, and cerebrospinal fluid.", "content": "I describe a highly sensitive and very specific assay for cyclic AMP and cyclic GMP in body fluids. An adaptation of the method of Harper and Brooker [j. cyclic Nucleotide Res. 1,207 (1975)], its advantage lies in the fact that the simple acetylation of the samples--a procedure developed by these workers--greatly increases specificity and sensitivity beyond those of previous methods and permits the measurement of femtomole quantities of both cyclic nucleotides without prepurification. Because the range of the cyclic AMP assay is 20-200 fmol, and that of cyclic GMP 10-15 fmol, experiments can be performed with use of only microliters of fluid. The method requires no extraction and thus no complicated corrections are necessary for analytical recovery.", "contents": "Radioimmunoassay for adenosine 3', 5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate in human blood, urine, and cerebrospinal fluid. I describe a highly sensitive and very specific assay for cyclic AMP and cyclic GMP in body fluids. An adaptation of the method of Harper and Brooker [j. cyclic Nucleotide Res. 1,207 (1975)], its advantage lies in the fact that the simple acetylation of the samples--a procedure developed by these workers--greatly increases specificity and sensitivity beyond those of previous methods and permits the measurement of femtomole quantities of both cyclic nucleotides without prepurification. Because the range of the cyclic AMP assay is 20-200 fmol, and that of cyclic GMP 10-15 fmol, experiments can be performed with use of only microliters of fluid. The method requires no extraction and thus no complicated corrections are necessary for analytical recovery."}
{"id": "PMID:189957", "title": "Disorders of fructose metabolism.", "content": "There are fundamental differences between the metabolic fate of fructose and of glucose. Whereas the metabolism of glucose is controlled by hormones such as insulin, fructose uptake and phosphorylation in the liver occurs independently of hormones and its ultimate metabolic fate is unpredictable. Essential fructosuria, a harmless inherited anomaly of fructose metabolism, is the least harmful of the disorders of fructose metabolism. Hereditary fructose intolerance and fructose-1,6-diphosphatase deficiency are discussed in greater detail with regard to biochemical abnormalities and clinical aspects. HFI is most serious in bottle-fed infants who cannot reject their sucrose-containing diet. Patients with HFI will have no clinical symptoms if kept on a fructose-free diet. In contrast, patients with fructose-1,6-diphosphatase deficiency can tolerate frucose. However, severe infections precipitate attacks of hypoglycaemia and lactic acidosis.", "contents": "Disorders of fructose metabolism. There are fundamental differences between the metabolic fate of fructose and of glucose. Whereas the metabolism of glucose is controlled by hormones such as insulin, fructose uptake and phosphorylation in the liver occurs independently of hormones and its ultimate metabolic fate is unpredictable. Essential fructosuria, a harmless inherited anomaly of fructose metabolism, is the least harmful of the disorders of fructose metabolism. Hereditary fructose intolerance and fructose-1,6-diphosphatase deficiency are discussed in greater detail with regard to biochemical abnormalities and clinical aspects. HFI is most serious in bottle-fed infants who cannot reject their sucrose-containing diet. Patients with HFI will have no clinical symptoms if kept on a fructose-free diet. In contrast, patients with fructose-1,6-diphosphatase deficiency can tolerate frucose. However, severe infections precipitate attacks of hypoglycaemia and lactic acidosis."}
{"id": "PMID:189959", "title": "Menkes kinky hair syndrome: Is it a treatable disorder?", "content": "A male infant with Menkes Kinky Hair Syndrome was treated with a 3-week course of cupric acetate infusions, which was terminated when he developed aminoaciduria. The lack of improvement seen in this infant is representative of the reported experience with parenteral copper therapy in this condition, and may be attributable to the presence of a clinically significant abnormality in copper metabolism in utero.", "contents": "Menkes kinky hair syndrome: Is it a treatable disorder? A male infant with Menkes Kinky Hair Syndrome was treated with a 3-week course of cupric acetate infusions, which was terminated when he developed aminoaciduria. The lack of improvement seen in this infant is representative of the reported experience with parenteral copper therapy in this condition, and may be attributable to the presence of a clinically significant abnormality in copper metabolism in utero."}
{"id": "PMID:189962", "title": "Neurocirculatory disorders of the foot.", "content": "There is a simple rationale for care of the dysvascular neuropathic foot. Either prevention or correction of deformities, or both, is of primary importance in the insensitive or poorly healing foot. Control of edema is necessary to achieve maximum healing potential. There are tools at hand to allow the orthopedic surgeon to judge arterial supply in addition to his clinical judgment. Interest in defensive footwear, appreciation of interface forces, and the application of standard operative techniques to this ever-present population can result in significant improvement in patient care.", "contents": "Neurocirculatory disorders of the foot. There is a simple rationale for care of the dysvascular neuropathic foot. Either prevention or correction of deformities, or both, is of primary importance in the insensitive or poorly healing foot. Control of edema is necessary to achieve maximum healing potential. There are tools at hand to allow the orthopedic surgeon to judge arterial supply in addition to his clinical judgment. Interest in defensive footwear, appreciation of interface forces, and the application of standard operative techniques to this ever-present population can result in significant improvement in patient care."}
{"id": "PMID:189971", "title": "Cutaneous lymphangiosarcoma of Stewart-Treves.", "content": "Lymphangiosarcoma of an edematous extremity is a highly malignant cutaneous neoplasm seen most often ten years after a successful radical mastectomy. The sarcoma presents with an ecchymosis and/or purplish cutaneous nodules on the edematous arm; it spreads through the bloodstream and is fatal in most cases. A case is presented which shows some typical and some unusual features of this disease.", "contents": "Cutaneous lymphangiosarcoma of Stewart-Treves. Lymphangiosarcoma of an edematous extremity is a highly malignant cutaneous neoplasm seen most often ten years after a successful radical mastectomy. The sarcoma presents with an ecchymosis and/or purplish cutaneous nodules on the edematous arm; it spreads through the bloodstream and is fatal in most cases. A case is presented which shows some typical and some unusual features of this disease."}
{"id": "PMID:189973", "title": "Bullous pemphigoid and rheumatoid arthritis with herpes simplex in the vesicular fluid.", "content": "Six cases of bullous perphigoid in association with rheumatoid arthritis have previously been reported in the literature. In the case reported in this paper, herpes simplex virus was found in the vesicular fluid. It is the first time this has been reported to this author's knowledge; this finding may contribute to the knowledge of the ultimate etiology of pemphigoid.", "contents": "Bullous pemphigoid and rheumatoid arthritis with herpes simplex in the vesicular fluid. Six cases of bullous perphigoid in association with rheumatoid arthritis have previously been reported in the literature. In the case reported in this paper, herpes simplex virus was found in the vesicular fluid. It is the first time this has been reported to this author's knowledge; this finding may contribute to the knowledge of the ultimate etiology of pemphigoid."}
{"id": "PMID:189974", "title": "Cytochemical detection of nucleoside diphosphatase activity in the central nervous system of the rat.", "content": "The cytochemical localization of nucleoside diphosphatase and thiamine pyrophosphatase occurs within the \"mature face\" of the Golgi apparatus and over the neurilemma in neurons of the cerebellum, the cerebral cortex and the brain stem. The hydrolytic reaction product of the brain enzyme differs from that of the liver in that it is not found in the endoplasmic reticulum or nuclear envelope. Hydrolysis of IDP, UDP or GDP is not greater than that of ADP or CDP in brain homogenates, in contrast to that found in the liver. The NDPase activity of brain homogenates is optimal at pH 7.2, stimulated by heavy metals and inhibited by uranyl nitrate. Thick section cytochemistry suggests that the reaction product is restricted to a network of polygonally shaped compartments. NDPase activity on the neurilemma may reflect the role of this enzyme in the synthesis of glycoproteins involved in neuronal surface recognition.", "contents": "Cytochemical detection of nucleoside diphosphatase activity in the central nervous system of the rat. The cytochemical localization of nucleoside diphosphatase and thiamine pyrophosphatase occurs within the \"mature face\" of the Golgi apparatus and over the neurilemma in neurons of the cerebellum, the cerebral cortex and the brain stem. The hydrolytic reaction product of the brain enzyme differs from that of the liver in that it is not found in the endoplasmic reticulum or nuclear envelope. Hydrolysis of IDP, UDP or GDP is not greater than that of ADP or CDP in brain homogenates, in contrast to that found in the liver. The NDPase activity of brain homogenates is optimal at pH 7.2, stimulated by heavy metals and inhibited by uranyl nitrate. Thick section cytochemistry suggests that the reaction product is restricted to a network of polygonally shaped compartments. NDPase activity on the neurilemma may reflect the role of this enzyme in the synthesis of glycoproteins involved in neuronal surface recognition."}
{"id": "PMID:189975", "title": "Evaluation of myocardial uptake of 99mtechnetium pyrophosphate in clinical exercise-induced ventricular ischemia.", "content": "Although acute infarction of the myocardium is known to accumulate 99mtechnetium pyrophosphate, it is not entirely clear that ischemia alone without necrosis does not result in abnormal uptake of 99mtechnetium pyrophosphate. The present study investigates whether transient myocardial ischemia is associated with localization of 99mtechnetium pyrophosphate by evaluating images obtained with the scintillation camera at rest and after exercise in 15 patients with unequivocal myocardial ischemia. All patients had angina pectoris, multivessel coronary artery stenoses by selective arteriographic studies, and electrocardiographic ischemic responses on treadmill exercise. Eleven of the 15 patients also underwent radionuclide imaging with 81rubidium at rest and after exercise; the results demonstrated scintigraphic ischemia. The scintiscans with 99mtechnetium pyrophosphate revealed no evidence of increased myocardial radioactivity after exercise compared to rest in 14 of the 15 patients. In contrast, myocardial activity was observed with 99mtechnetium pyrophosphate after treadmill exertion in the remaining patient, in whom a small subendocardial infarction appeared to have occurred with the exercise. It is concluded from these results that transient myocardial ischemia does not cause localization of 99mtechnetium pyrophosphate. These findings support the specificity of abnormal localization of 99mtechnetium pyrophosphate for acute myocardial infarction.", "contents": "Evaluation of myocardial uptake of 99mtechnetium pyrophosphate in clinical exercise-induced ventricular ischemia. Although acute infarction of the myocardium is known to accumulate 99mtechnetium pyrophosphate, it is not entirely clear that ischemia alone without necrosis does not result in abnormal uptake of 99mtechnetium pyrophosphate. The present study investigates whether transient myocardial ischemia is associated with localization of 99mtechnetium pyrophosphate by evaluating images obtained with the scintillation camera at rest and after exercise in 15 patients with unequivocal myocardial ischemia. All patients had angina pectoris, multivessel coronary artery stenoses by selective arteriographic studies, and electrocardiographic ischemic responses on treadmill exercise. Eleven of the 15 patients also underwent radionuclide imaging with 81rubidium at rest and after exercise; the results demonstrated scintigraphic ischemia. The scintiscans with 99mtechnetium pyrophosphate revealed no evidence of increased myocardial radioactivity after exercise compared to rest in 14 of the 15 patients. In contrast, myocardial activity was observed with 99mtechnetium pyrophosphate after treadmill exertion in the remaining patient, in whom a small subendocardial infarction appeared to have occurred with the exercise. It is concluded from these results that transient myocardial ischemia does not cause localization of 99mtechnetium pyrophosphate. These findings support the specificity of abnormal localization of 99mtechnetium pyrophosphate for acute myocardial infarction."}
{"id": "PMID:189976", "title": "Dipyridamole, an inhibitor of mengovirus replication in FL and L cells.", "content": "Dipyridamole showed an antiviral activity aganinst mengovirus in FL cells using the agar diffusion plaque inhibition test, plaque reduction test, tube titration test, and virus yield test after one replication cycle. With the last two tests mentioned above the inhibitory action was also confirmed in L cells. In consequence of the known transport inhibition of uridine into the cell in presence of dipyridamole only a very small incorporation of 3H-uridine into acid-insoluble material could be demonstrated. Applying the method of prelabelling of FL cells at 16 degrees C for 1 h with subsequent addition of dipyridamole the drug failed to show an effect on cellular RNA synthesis per se in uninfected cells whereas the viral RNA synthesis in mengo-virus-infected L cells was completely depressed.", "contents": "Dipyridamole, an inhibitor of mengovirus replication in FL and L cells. Dipyridamole showed an antiviral activity aganinst mengovirus in FL cells using the agar diffusion plaque inhibition test, plaque reduction test, tube titration test, and virus yield test after one replication cycle. With the last two tests mentioned above the inhibitory action was also confirmed in L cells. In consequence of the known transport inhibition of uridine into the cell in presence of dipyridamole only a very small incorporation of 3H-uridine into acid-insoluble material could be demonstrated. Applying the method of prelabelling of FL cells at 16 degrees C for 1 h with subsequent addition of dipyridamole the drug failed to show an effect on cellular RNA synthesis per se in uninfected cells whereas the viral RNA synthesis in mengo-virus-infected L cells was completely depressed."}
{"id": "PMID:189982", "title": "Sigma effects of nalorphine in the chronic spinal dog.", "content": "The effects of graded doses of nalorphine and morphine were studied in nondependent chronic spinal dogs. Morphine and low doses of nalorphine produced behavioral changes characterized by indifference, whereas the largest dose of nalorphine produced canine delirium indistinguishable from that produced by SKF-10, 047 or cyclazocine. Nalorphine depressed the flexor reflex; however, a plateau was observed. The data suggest that nalorphine is a partial agonist of the kappa type and a sigma agonist in addition to being a competitive antagonist at the mu receptor, and further, that the dysphoric and hallucinogenic effects of nalorphine-like drugs are due to their sigma activity.", "contents": "Sigma effects of nalorphine in the chronic spinal dog. The effects of graded doses of nalorphine and morphine were studied in nondependent chronic spinal dogs. Morphine and low doses of nalorphine produced behavioral changes characterized by indifference, whereas the largest dose of nalorphine produced canine delirium indistinguishable from that produced by SKF-10, 047 or cyclazocine. Nalorphine depressed the flexor reflex; however, a plateau was observed. The data suggest that nalorphine is a partial agonist of the kappa type and a sigma agonist in addition to being a competitive antagonist at the mu receptor, and further, that the dysphoric and hallucinogenic effects of nalorphine-like drugs are due to their sigma activity."}
{"id": "PMID:189981", "title": "Ultradian rhythms in the perception of two apparent motions.", "content": "Fourteen young adults were tested  on the spiral after-effect every 5 min and on the beta movement every 20 min for 8 continuous hrs. Time series analysis revealed significant 100-min rhythms in the perception of the two illusions, which also appeared to be sychronized across the experimental periods.", "contents": "Ultradian rhythms in the perception of two apparent motions. Fourteen young adults were tested  on the spiral after-effect every 5 min and on the beta movement every 20 min for 8 continuous hrs. Time series analysis revealed significant 100-min rhythms in the perception of the two illusions, which also appeared to be sychronized across the experimental periods."}
{"id": "PMID:189988", "title": "[Changes in the concentration of biogenic monoamines in different brain regions under the influence of centrophenoxine (experiments on rats)].", "content": "The authors administered 50 mg/body weight of centrophenoxine in white rats i.p. for five susseccive days. The content of serotonine in the cerebral cortex, brain stem and cerebellum increased statistically significant in the rats, injected with centrophenoxine. The levels of noradrenaline and dopamine in the brain stem were raised also significantly. Centrophenoxine did not alter the content of cyclic AMP and the activity of phosphodiesterase in the cerebral cortex and brain stem. These data gave foundation to the authors to suggest that in the mechanism of action of centrophenoxine a significant role is given to the changes, induced by this preparation in the content of biogenic amines in the brain stem.", "contents": "[Changes in the concentration of biogenic monoamines in different brain regions under the influence of centrophenoxine (experiments on rats)]. The authors administered 50 mg/body weight of centrophenoxine in white rats i.p. for five susseccive days. The content of serotonine in the cerebral cortex, brain stem and cerebellum increased statistically significant in the rats, injected with centrophenoxine. The levels of noradrenaline and dopamine in the brain stem were raised also significantly. Centrophenoxine did not alter the content of cyclic AMP and the activity of phosphodiesterase in the cerebral cortex and brain stem. These data gave foundation to the authors to suggest that in the mechanism of action of centrophenoxine a significant role is given to the changes, induced by this preparation in the content of biogenic amines in the brain stem."}
{"id": "PMID:189989", "title": "Control of bioactive corticotropin release from the neuro-intermediate lobe of the rat pituitary in vitro.", "content": "The purpose of this study was to identify agents capable of regulating the release of biologically active ACTH from the isolated neuro-intermediate lobe of the rat pituitary. Agents found to be potent secretagogues included acetylcholine (100 mug/ml), hypothalamic stalk-median eminence extract (0.33 eq), arginine antidiuretic hormone (100 mU/ml) and serotonin (100 mug/ml). Lower doses of arginine antidiuretic hormone (5.5 mU/ml) and serotonin (2 mug/ml) were ineffective. Dopamine 2 and 5 mug/ml) inhibited the release of biologically active ACTH whereas norepinephrine (5 mug/ml) did not. Dexamethasone (0.25 mug/ml) did not alter the basal or stimulated release of ACTH from the isolated neuro-intermediate lobe in contrast to its effect on ACTH release from the isolated anterior pituitary. Similarly, the tripeptide, prolyl-leucyl-glycinamide, which has been reported by some to inhibit MSH release, had no effect on either the basal or stimulated release of ACTH. The data suggest that regulation of ACTH release from the neuro-intermediate lobe in vivo may involve both stimulatory (acetylcholine) and inhibitory (dopamine) inputs.", "contents": "Control of bioactive corticotropin release from the neuro-intermediate lobe of the rat pituitary in vitro. The purpose of this study was to identify agents capable of regulating the release of biologically active ACTH from the isolated neuro-intermediate lobe of the rat pituitary. Agents found to be potent secretagogues included acetylcholine (100 mug/ml), hypothalamic stalk-median eminence extract (0.33 eq), arginine antidiuretic hormone (100 mU/ml) and serotonin (100 mug/ml). Lower doses of arginine antidiuretic hormone (5.5 mU/ml) and serotonin (2 mug/ml) were ineffective. Dopamine 2 and 5 mug/ml) inhibited the release of biologically active ACTH whereas norepinephrine (5 mug/ml) did not. Dexamethasone (0.25 mug/ml) did not alter the basal or stimulated release of ACTH from the isolated neuro-intermediate lobe in contrast to its effect on ACTH release from the isolated anterior pituitary. Similarly, the tripeptide, prolyl-leucyl-glycinamide, which has been reported by some to inhibit MSH release, had no effect on either the basal or stimulated release of ACTH. The data suggest that regulation of ACTH release from the neuro-intermediate lobe in vivo may involve both stimulatory (acetylcholine) and inhibitory (dopamine) inputs."}
{"id": "PMID:189990", "title": "Control of bovine adrenal cortical cell proliferation by fibroblast growth factor. Lack of effect of epidermal growth factor.", "content": "Primary functional bovine adrenal cortical cell cultures have been developed to study the factors controlling adrenal cell growth. Cells were prepared by the collagenase technique and maintained in F-12 medium containing fetal calf serum and horse serum. Cells contained abundant lipid as demonstrated by staining with Oil Red O and showed strongly positive staining for delta5,3beta-hydroxysteroid dehydrogenase. ACTH inhibited DNA synthesis and stimulated steriodogenesis in these cells. Fibroblast growth factor (FGF) was shown to be a potent stimulator of the growth of normal bovine adrenal cortical cells maintained in tissue culture. The minimal effective dose of FGF was 1 ng/ml with maximal effects being observed at 100 ng/ml. The effect of FGF was dependent on the serum concentration. Inclusion of FGF in F-12 medium containing serum permitted cloning of functional bovine adrenal cortical cells from cultures seeded at low density (4 cells/cm2). ACTH inhibited the mitogenic effects of FGF. In addition to its mitogenic action, FGF is a migratory factor for bovine adrenal cortical cells. Though ACTH inhibited the mitogenic effects of FGF, it did not block the migratory activity. Epidermal growth factor did not affect the growth of either normal bovine adrenal or functional mouse adrenal tumor cells (Y-1) in tissue culture. FGF is the first direct mitogen identified for adrenal cortical cells; ACTH opposes this mitogenic action and functions directly as a differentiate function signal.", "contents": "Control of bovine adrenal cortical cell proliferation by fibroblast growth factor. Lack of effect of epidermal growth factor. Primary functional bovine adrenal cortical cell cultures have been developed to study the factors controlling adrenal cell growth. Cells were prepared by the collagenase technique and maintained in F-12 medium containing fetal calf serum and horse serum. Cells contained abundant lipid as demonstrated by staining with Oil Red O and showed strongly positive staining for delta5,3beta-hydroxysteroid dehydrogenase. ACTH inhibited DNA synthesis and stimulated steriodogenesis in these cells. Fibroblast growth factor (FGF) was shown to be a potent stimulator of the growth of normal bovine adrenal cortical cells maintained in tissue culture. The minimal effective dose of FGF was 1 ng/ml with maximal effects being observed at 100 ng/ml. The effect of FGF was dependent on the serum concentration. Inclusion of FGF in F-12 medium containing serum permitted cloning of functional bovine adrenal cortical cells from cultures seeded at low density (4 cells/cm2). ACTH inhibited the mitogenic effects of FGF. In addition to its mitogenic action, FGF is a migratory factor for bovine adrenal cortical cells. Though ACTH inhibited the mitogenic effects of FGF, it did not block the migratory activity. Epidermal growth factor did not affect the growth of either normal bovine adrenal or functional mouse adrenal tumor cells (Y-1) in tissue culture. FGF is the first direct mitogen identified for adrenal cortical cells; ACTH opposes this mitogenic action and functions directly as a differentiate function signal."}
{"id": "PMID:189991", "title": "A superfusion system technique for the study of the sites of action of glucocorticoids in the rat hypothalamus-pituitary-adrenal system in vitro. I. Pituitary cell superfusion.", "content": "Rat anterior pituitary cells were placed in a superfusion column and were stimulated by rat hypothalamic extract. The rate of ACTH secretion was monitored by collecting fractions eluting from the column every 2 min. Dispersed rat adrenocortical cells were used to determine the amounts of ACTH in the superfusate. ACTH appeared in the medium 6-12 sec after stimulation of the cells. A linear log dose-response relationship existed between 1/8 to 1 rat hypothalamus extract and the amounts of ACTH released. Repeated pulses of CRF stimulation of the same column of pituitary cells resulted in repeated, identical peaks of ACTH. Constant stimulation caused a plateau in hormone release that lasted as long as the stimulus was present. The stimulated, but not the basal ACTH release, could be inhibited by superfusion with corticosterone in vitro (0.2 mug/ml), or by treating the pituitary donor animal in vivo with corticosterone (5 mg/100g BW), cortisol or dexamethasone. Adrenalectomy of the donor animal caused increases in the basal and the stimulated ACTH release.", "contents": "A superfusion system technique for the study of the sites of action of glucocorticoids in the rat hypothalamus-pituitary-adrenal system in vitro. I. Pituitary cell superfusion. Rat anterior pituitary cells were placed in a superfusion column and were stimulated by rat hypothalamic extract. The rate of ACTH secretion was monitored by collecting fractions eluting from the column every 2 min. Dispersed rat adrenocortical cells were used to determine the amounts of ACTH in the superfusate. ACTH appeared in the medium 6-12 sec after stimulation of the cells. A linear log dose-response relationship existed between 1/8 to 1 rat hypothalamus extract and the amounts of ACTH released. Repeated pulses of CRF stimulation of the same column of pituitary cells resulted in repeated, identical peaks of ACTH. Constant stimulation caused a plateau in hormone release that lasted as long as the stimulus was present. The stimulated, but not the basal ACTH release, could be inhibited by superfusion with corticosterone in vitro (0.2 mug/ml), or by treating the pituitary donor animal in vivo with corticosterone (5 mg/100g BW), cortisol or dexamethasone. Adrenalectomy of the donor animal caused increases in the basal and the stimulated ACTH release."}
{"id": "PMID:189992", "title": "Cortisol secretion and clearance in the rhesus monkey.", "content": "Cortisol secretory patterns were studied in two chair-adapted rhesus monkeys by simultaneous measurement of plasma concentration and specific activity of cortisol after an iv bolus of 14C-labeled hormone. The results indicated that fluctuating plasma cortisol concentrations are the result of episodic secretion by the adrenal cortex. Specific activity changes during these spontaneous secretory bursts indicated occasional submaximal activity. In addition, cortisol secretory rates calculated during basal (20.4 mug/min) and ACTH-stimulated (28.4mug/min) conditions in a total of seven monkeys were significantly different (P less than 0.05), further demonstrating that spontaneous secretory bursts were usually sub-maximal. From plasma samples collected at 10 min intervals, a cortisol distribution t1/2 of 6 min and a clearance t1/2 of 66 min were found. The apparent volume of distribution for this hormone was 4.8 liters, a value far in excess of extracellular fluid volume estimates. The circadian pattern of plasma cortisol in these monkeys resembled that reported for man, but monkeys had twice as many episodic bursts and over twice the mean cortisol levels as man. However, the 24 h production rate was 10.5 mg, a value within the range of human production.", "contents": "Cortisol secretion and clearance in the rhesus monkey. Cortisol secretory patterns were studied in two chair-adapted rhesus monkeys by simultaneous measurement of plasma concentration and specific activity of cortisol after an iv bolus of 14C-labeled hormone. The results indicated that fluctuating plasma cortisol concentrations are the result of episodic secretion by the adrenal cortex. Specific activity changes during these spontaneous secretory bursts indicated occasional submaximal activity. In addition, cortisol secretory rates calculated during basal (20.4 mug/min) and ACTH-stimulated (28.4mug/min) conditions in a total of seven monkeys were significantly different (P less than 0.05), further demonstrating that spontaneous secretory bursts were usually sub-maximal. From plasma samples collected at 10 min intervals, a cortisol distribution t1/2 of 6 min and a clearance t1/2 of 66 min were found. The apparent volume of distribution for this hormone was 4.8 liters, a value far in excess of extracellular fluid volume estimates. The circadian pattern of plasma cortisol in these monkeys resembled that reported for man, but monkeys had twice as many episodic bursts and over twice the mean cortisol levels as man. However, the 24 h production rate was 10.5 mg, a value within the range of human production."}
{"id": "PMID:189993", "title": "The mechanism of damping of the serum thyroxine and triidothyronine levels caused by increasing thyrotropin dosage in mice.", "content": "The time course of the effect of bovine TSH (bTSH) on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was measured in the normal mouse. The basal, unstimulated levels were 3.2+/-1.1 mug/100 ml T4 and 104+/-25 ng/100 ml T3 (mean+/-SD). With doses of bTSH from 0.5 to 100 mU the peak levels of the thyroid hormones were only 2.6 and 1.8 times the basal level for T4 and T3, respectively. With increasing doses of bTSH there was a proportional prolongation of the increased serum levels of thyroid hormones, i.e., about 2 h for 0.5mU to 12 h for 100 mU TSH. The integrated response with time was linearly related to the log dose. This would suggest a control mechanism which prevents excessive concentration of thyroid hormones in the serum. This pattern of response to TSH differs somewhat from that obtained by following radioiodine release in the McKenzie type bio-assay. To avoid the problems of changing blood concentrations of thyroid hormones and TSH, the release of T4 and T3 from the mouse thyroid was measured in vitro. The secretion increased with bTSH concentrations in the range of 0.02-0.8 mU/ml for T4 and 0.02-0.4 mU/ml for T3. The maximal response was 8.8+/-0.5 ng T4/3h/thyroid and 3.6+/-0.3 ng T3/3h/thyroid as against the basal secretion of 2.4+/-0.2ng T4 and 0.8+/-0.1 ng T3 (mean+/-SEM). Further in crease in bTSH concentration was associated with a decreased rate of thyroid hormone release. Thyroidal cAMP accumulation was enhanced with increasing bTSH concentration, even when there was a decrease in secretion. The dichotomy in the dose-response pattern between the two parameters indicated that the effect of high TSH concentrations on the release was induced at a step beyond cAMP accumulation. This was corroborated by the similar pattern of release induced by increasing concentration of DBcAMP. These findings indicate the existence of an intrathyroidal autoregulatory mechanism which prevents excess increase of thyroid hormone levels in the blood.", "contents": "The mechanism of damping of the serum thyroxine and triidothyronine levels caused by increasing thyrotropin dosage in mice. The time course of the effect of bovine TSH (bTSH) on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was measured in the normal mouse. The basal, unstimulated levels were 3.2+/-1.1 mug/100 ml T4 and 104+/-25 ng/100 ml T3 (mean+/-SD). With doses of bTSH from 0.5 to 100 mU the peak levels of the thyroid hormones were only 2.6 and 1.8 times the basal level for T4 and T3, respectively. With increasing doses of bTSH there was a proportional prolongation of the increased serum levels of thyroid hormones, i.e., about 2 h for 0.5mU to 12 h for 100 mU TSH. The integrated response with time was linearly related to the log dose. This would suggest a control mechanism which prevents excessive concentration of thyroid hormones in the serum. This pattern of response to TSH differs somewhat from that obtained by following radioiodine release in the McKenzie type bio-assay. To avoid the problems of changing blood concentrations of thyroid hormones and TSH, the release of T4 and T3 from the mouse thyroid was measured in vitro. The secretion increased with bTSH concentrations in the range of 0.02-0.8 mU/ml for T4 and 0.02-0.4 mU/ml for T3. The maximal response was 8.8+/-0.5 ng T4/3h/thyroid and 3.6+/-0.3 ng T3/3h/thyroid as against the basal secretion of 2.4+/-0.2ng T4 and 0.8+/-0.1 ng T3 (mean+/-SEM). Further in crease in bTSH concentration was associated with a decreased rate of thyroid hormone release. Thyroidal cAMP accumulation was enhanced with increasing bTSH concentration, even when there was a decrease in secretion. The dichotomy in the dose-response pattern between the two parameters indicated that the effect of high TSH concentrations on the release was induced at a step beyond cAMP accumulation. This was corroborated by the similar pattern of release induced by increasing concentration of DBcAMP. These findings indicate the existence of an intrathyroidal autoregulatory mechanism which prevents excess increase of thyroid hormone levels in the blood."}
{"id": "PMID:189994", "title": "Functional clones of pituitary cells derived from Rathke's pouch epithelium of fetal rats.", "content": "Sixty-five clonal strains fo anterior pituitary cells have been established from Rathke's pouch epithelium of fetal rats. Radioimmunoassay of the conditioned media has shown that some clones produce only prolactin, some produce prolactin and growth hormone and others produce prolactin, growth hormone and ACTH. The clonal cells have retained a normal diploid karyotype for extended periods of time in culture. The results indicate that differentiation into somatotrophs, coricotrophs and prolactin cells can occur in vitro from a single progenitor cell.", "contents": "Functional clones of pituitary cells derived from Rathke's pouch epithelium of fetal rats. Sixty-five clonal strains fo anterior pituitary cells have been established from Rathke's pouch epithelium of fetal rats. Radioimmunoassay of the conditioned media has shown that some clones produce only prolactin, some produce prolactin and growth hormone and others produce prolactin, growth hormone and ACTH. The clonal cells have retained a normal diploid karyotype for extended periods of time in culture. The results indicate that differentiation into somatotrophs, coricotrophs and prolactin cells can occur in vitro from a single progenitor cell."}
{"id": "PMID:189995", "title": "Adenylyl cyclase and cyclic nucleotide phosphodiesterases in GH-Strains of rat pituitary cells.", "content": "The properties of adenylyl cyclase and cyclic nucleotide phosphodiesterases from GH-strains of rat pituitary tumor cells have been investigated. Adenylyl cyclase was inhibited by calcium ion and stimulated by fluoride ion, 5'-guanylylimidodiphosphate and by prior treatment of intact releasing hormone (TRH), which stimulates prolactin releasing hormone (TRH), which stimulates prolactin release and synthesis in GH-cells, did not cause a significant stimulation of adenylyl cyclase activity under a wide variety of assay conditions; under the same conditions, [3H]TRH bound to a previously characterized membrane receptor. GH-cells contain phosphodiesterase activity catalyzing the hydrolysis of cAMP which gives nonliner Lineweaver-Burk plots with apparent Km's for cAMP of 1.5 muM and 4mM. TRH did not affect the activity of cyclic nucleotide phosphodiesterase at high or low cAMP concentrations when added to broken cell preparations. Treatment of intact cells with TRH caused no changes in the total adenylyl cyclase and cyclic nucleotide phosphodiesterase activites within the first 2 h of incubation, when stimulation of prolactin release occurs, but did lead to slight decrease in adenylyl cyclase and the apparent low Km phosphodiesterase after 72 h of treatment.", "contents": "Adenylyl cyclase and cyclic nucleotide phosphodiesterases in GH-Strains of rat pituitary cells. The properties of adenylyl cyclase and cyclic nucleotide phosphodiesterases from GH-strains of rat pituitary tumor cells have been investigated. Adenylyl cyclase was inhibited by calcium ion and stimulated by fluoride ion, 5'-guanylylimidodiphosphate and by prior treatment of intact releasing hormone (TRH), which stimulates prolactin releasing hormone (TRH), which stimulates prolactin release and synthesis in GH-cells, did not cause a significant stimulation of adenylyl cyclase activity under a wide variety of assay conditions; under the same conditions, [3H]TRH bound to a previously characterized membrane receptor. GH-cells contain phosphodiesterase activity catalyzing the hydrolysis of cAMP which gives nonliner Lineweaver-Burk plots with apparent Km's for cAMP of 1.5 muM and 4mM. TRH did not affect the activity of cyclic nucleotide phosphodiesterase at high or low cAMP concentrations when added to broken cell preparations. Treatment of intact cells with TRH caused no changes in the total adenylyl cyclase and cyclic nucleotide phosphodiesterase activites within the first 2 h of incubation, when stimulation of prolactin release occurs, but did lead to slight decrease in adenylyl cyclase and the apparent low Km phosphodiesterase after 72 h of treatment."}
{"id": "PMID:189996", "title": "The influence of propranolol on the thyrotropin receptor.", "content": "Propranolol, a beta adrenergic blocking drug, is known to inhibit the thyrotropin (TSH) stimulation of adenosine-3',5'-monophosphate (cyclic AMP production in thyroid membranes but the mechansim of this inhibitory action is known. We have therefore investigated the influence of propranolol on the binding of 125I-labelled TSH to human thyroid membranes. Both d- and l-propranolol were found to enhance the binding of 125I-labelled TSH to thyroid membranes. The amount of label bound increased from about 30% in the absence of propranolol to about 60% in the presence of 3.3 x 10(-3)M propranolol. Scatchard analysis of the binding data indicated that propranolol increased the association constant of the thyrotropin-thyrotropin receptor interaction. Practolol, lithium carbonate, methimazole, and somatostatin had no effect on thyrotropin binding. This effect of propranolol appeared to be due to a direct reversible action of propranolol on the thyroid membranes and could be attributed to the membrane-disrupting properties of the drug rather than its beta-blocking activity. The increased TSH receptor occupancy which resulted from the increased association constant of the TSH-thyroid membrane interaction corresponded with a decrease in TSH-stimulated cyclic AMP formation. These data could indicate that propranolol reduced the efficiency of the receptor-adenylyl cyclase coupling system.", "contents": "The influence of propranolol on the thyrotropin receptor. Propranolol, a beta adrenergic blocking drug, is known to inhibit the thyrotropin (TSH) stimulation of adenosine-3',5'-monophosphate (cyclic AMP production in thyroid membranes but the mechansim of this inhibitory action is known. We have therefore investigated the influence of propranolol on the binding of 125I-labelled TSH to human thyroid membranes. Both d- and l-propranolol were found to enhance the binding of 125I-labelled TSH to thyroid membranes. The amount of label bound increased from about 30% in the absence of propranolol to about 60% in the presence of 3.3 x 10(-3)M propranolol. Scatchard analysis of the binding data indicated that propranolol increased the association constant of the thyrotropin-thyrotropin receptor interaction. Practolol, lithium carbonate, methimazole, and somatostatin had no effect on thyrotropin binding. This effect of propranolol appeared to be due to a direct reversible action of propranolol on the thyroid membranes and could be attributed to the membrane-disrupting properties of the drug rather than its beta-blocking activity. The increased TSH receptor occupancy which resulted from the increased association constant of the TSH-thyroid membrane interaction corresponded with a decrease in TSH-stimulated cyclic AMP formation. These data could indicate that propranolol reduced the efficiency of the receptor-adenylyl cyclase coupling system."}
{"id": "PMID:189997", "title": "Pulmonary changes induced by amphophilic drugs.", "content": "Administration of amphophilic drugs to experimental animals causes formation of myeloid bodies in many cell types, accumulation of foamy macrophages in pulmonary alveoli, and pulmonary alveolar proteinosis. These changes are the result of an interaction between the drugs and phospholipids which leads to an alteration in physicochemical properties of the phospholipids. Impairment of the digestion of altered pulmonary secretions in phagosomes of macrophages results in accumulation of foam cells in pulmonary alveoli. Impairment of the metabolism of altered phospholipids removed by autophagy induces an accumulation of myeloid bodies. In summary, administration of amphophilic compounds causes a drug-induced lysosomal disease or generalized phospholipidosis.", "contents": "Pulmonary changes induced by amphophilic drugs. Administration of amphophilic drugs to experimental animals causes formation of myeloid bodies in many cell types, accumulation of foamy macrophages in pulmonary alveoli, and pulmonary alveolar proteinosis. These changes are the result of an interaction between the drugs and phospholipids which leads to an alteration in physicochemical properties of the phospholipids. Impairment of the digestion of altered pulmonary secretions in phagosomes of macrophages results in accumulation of foam cells in pulmonary alveoli. Impairment of the metabolism of altered phospholipids removed by autophagy induces an accumulation of myeloid bodies. In summary, administration of amphophilic compounds causes a drug-induced lysosomal disease or generalized phospholipidosis."}
{"id": "PMID:189998", "title": "Electron spin resonance (ESR) study of cigarette smoke by use of spin trapping techniques.", "content": "The technique of spin trapping has been applied to the gas phase of cigarette smoke to identify and quantify the radicals present. It was found that radicals could be trapped only if the smoke was filtered. Three spin traps were used: N-tert-butyl-alpha-phenyl nitrone (PBN). 5,5-dimethyl-delta1-pyrroline-1-oxide (DMPO) and alpha-[3,5-di-tert-butyl-4-hydroxyphenyl)-N-tert-butyl nitrone (OHPBN). From the electron spin resonance (ESR) splitting constants of the radicals produced by the reaction of smoke radicals with the spin traps and also from the effec of varying the path length between the cigarette and the spin trap solution, it is concluded that three types of signals are observed. Type I signals indicate the presence of oxygenated radicals which appear to be a mixture of alkoxy radicals (RO) and aroyloxy (ArCO2-) radicals. Our data do not allow conclusions about the nature of the R or Ar groups in these two oxy radicals; however, considerations based on lifetimes suggest that the R group probably is tertiary. Type II and III signals are not typical spectra of spin adducts. Instead, we believe they result from reaction of smoke (and probably radicals in smoke) with the PBN spin trap and indicate that smoke has the ability to effect one-electron oxidations. Only type I signals are observed with DMPO and OHPBN. A quantitative study shows that 4 x 10(14) spins/puff are present in the smoke, in contrast with the result of a recent study which used a very different method for determining the radical content of smoke. A discussion of the nature of the radicals in smoke and some tentative conclusions are presented.", "contents": "Electron spin resonance (ESR) study of cigarette smoke by use of spin trapping techniques. The technique of spin trapping has been applied to the gas phase of cigarette smoke to identify and quantify the radicals present. It was found that radicals could be trapped only if the smoke was filtered. Three spin traps were used: N-tert-butyl-alpha-phenyl nitrone (PBN). 5,5-dimethyl-delta1-pyrroline-1-oxide (DMPO) and alpha-[3,5-di-tert-butyl-4-hydroxyphenyl)-N-tert-butyl nitrone (OHPBN). From the electron spin resonance (ESR) splitting constants of the radicals produced by the reaction of smoke radicals with the spin traps and also from the effec of varying the path length between the cigarette and the spin trap solution, it is concluded that three types of signals are observed. Type I signals indicate the presence of oxygenated radicals which appear to be a mixture of alkoxy radicals (RO) and aroyloxy (ArCO2-) radicals. Our data do not allow conclusions about the nature of the R or Ar groups in these two oxy radicals; however, considerations based on lifetimes suggest that the R group probably is tertiary. Type II and III signals are not typical spectra of spin adducts. Instead, we believe they result from reaction of smoke (and probably radicals in smoke) with the PBN spin trap and indicate that smoke has the ability to effect one-electron oxidations. Only type I signals are observed with DMPO and OHPBN. A quantitative study shows that 4 x 10(14) spins/puff are present in the smoke, in contrast with the result of a recent study which used a very different method for determining the radical content of smoke. A discussion of the nature of the radicals in smoke and some tentative conclusions are presented."}
{"id": "PMID:189999", "title": "Purification and control of bovine adrenal cortical cholesterol ester hydrolase and evidence for the activation of the enzyme by a phosphorylation.", "content": "A procedure for the purification of cholesterol ester hydrolase from bovine adrenal cortical 105000 x g supernatant is described. Preincubation of a crude enzyme extract with [gamma-32P]ATP followed by purification resulted in the isolation of a phosphorylated preparation of cholesterol ester hydrolase. The phosphorylated cholesterol ester hydrolase appeared to be composed of 4 subunits, each having a molecular weight of 41000 +/- 280, only one of which may be phosphorylated. Preincubation of the crude enzyme preparation with [alpha-32P]ATP followed by purification did not produce a phosphorylated preparation of cholesterol ester hydrolase. Cyclic-AMP-dependent protein kinase, cyclic AMP, ATP and magnesium ions were required for activation of purified cholesterol ester hydrolase in vitro and the time course of activation closely paralleled the time course of phosphorylation of the enzyme. The addition of ATP, cyclic AMP and magnesium ions to the bovine adrenal cortical 105000 x g supernatant produced a 2.5-fold stimulation in cholesterol ester hydrolase activity. This stimulation was abolished if protein kinase inhibitor was added prior to the addition of ATP cyclic AMP and magensium ions. The addition of magnesium ions or calcium ions to a crude preparation of cholesterol ester hydrolase was found to inhibit activity; however the same additions made to a purified preparation of cholesterol ester hydrolase were not inhibitory. The decrease in cholesterol ester hydrolase activity on incubation with magnesium ion was accompanied by a loss of 32P radioactivity from the protein. Preincubation of a crude preparation of cholesterol ester hydrolase with alkaline phosphatase resulted in a deactivation of cholesterol ester hydrolase. It is suggested that bovine adrenal cortex cholesterol ester hydrolase is activated by a phosphorylation catalysed by a cyclic-AMP-dependent protein kinase. Deactivation of cholesterol ester hydrolase is accomplished by dephosphorylation catalysed by a phosphoprotein phosphatase, dependent on magnesium or calcium ions.", "contents": "Purification and control of bovine adrenal cortical cholesterol ester hydrolase and evidence for the activation of the enzyme by a phosphorylation. A procedure for the purification of cholesterol ester hydrolase from bovine adrenal cortical 105000 x g supernatant is described. Preincubation of a crude enzyme extract with [gamma-32P]ATP followed by purification resulted in the isolation of a phosphorylated preparation of cholesterol ester hydrolase. The phosphorylated cholesterol ester hydrolase appeared to be composed of 4 subunits, each having a molecular weight of 41000 +/- 280, only one of which may be phosphorylated. Preincubation of the crude enzyme preparation with [alpha-32P]ATP followed by purification did not produce a phosphorylated preparation of cholesterol ester hydrolase. Cyclic-AMP-dependent protein kinase, cyclic AMP, ATP and magnesium ions were required for activation of purified cholesterol ester hydrolase in vitro and the time course of activation closely paralleled the time course of phosphorylation of the enzyme. The addition of ATP, cyclic AMP and magnesium ions to the bovine adrenal cortical 105000 x g supernatant produced a 2.5-fold stimulation in cholesterol ester hydrolase activity. This stimulation was abolished if protein kinase inhibitor was added prior to the addition of ATP cyclic AMP and magensium ions. The addition of magnesium ions or calcium ions to a crude preparation of cholesterol ester hydrolase was found to inhibit activity; however the same additions made to a purified preparation of cholesterol ester hydrolase were not inhibitory. The decrease in cholesterol ester hydrolase activity on incubation with magnesium ion was accompanied by a loss of 32P radioactivity from the protein. Preincubation of a crude preparation of cholesterol ester hydrolase with alkaline phosphatase resulted in a deactivation of cholesterol ester hydrolase. It is suggested that bovine adrenal cortex cholesterol ester hydrolase is activated by a phosphorylation catalysed by a cyclic-AMP-dependent protein kinase. Deactivation of cholesterol ester hydrolase is accomplished by dephosphorylation catalysed by a phosphoprotein phosphatase, dependent on magnesium or calcium ions."}
{"id": "PMID:190000", "title": "Adenosine 3':5'-monophosphate metabolism and turnover in dog thyroid slices.", "content": "The metabolism and turnover of adenosine 3':5'-monophosphate (cyclic AMP) have been studied in intact thyroid cells incubated in vitro. Thyroid slices have been stimulated by 1 mU thyrotropin/ml, then washed with buffer, or with buffer containing thyrotropin antibody, or trypsin so as to cut off the stimulation. The decline of cyclic AMP levels has been followed and the time required to decrease this level to half of the initial value estimated. Computer simulation taking into account the penetration of trypsin in the slices, the kinetics of thyrotropin inactivation and the relation between thyrotropin concentration and cyclic AMP concentration at the steady state has made it possible to estimate the true cellular half-life of cyclic AMP in the stimulated cell to 1 min 50 s. The method provides an experimental approach to the demonstration in intact cells of effective on cyclic AMP disappearance. The methodology of the calculation of half-life and turnover from such data is discussed.", "contents": "Adenosine 3':5'-monophosphate metabolism and turnover in dog thyroid slices. The metabolism and turnover of adenosine 3':5'-monophosphate (cyclic AMP) have been studied in intact thyroid cells incubated in vitro. Thyroid slices have been stimulated by 1 mU thyrotropin/ml, then washed with buffer, or with buffer containing thyrotropin antibody, or trypsin so as to cut off the stimulation. The decline of cyclic AMP levels has been followed and the time required to decrease this level to half of the initial value estimated. Computer simulation taking into account the penetration of trypsin in the slices, the kinetics of thyrotropin inactivation and the relation between thyrotropin concentration and cyclic AMP concentration at the steady state has made it possible to estimate the true cellular half-life of cyclic AMP in the stimulated cell to 1 min 50 s. The method provides an experimental approach to the demonstration in intact cells of effective on cyclic AMP disappearance. The methodology of the calculation of half-life and turnover from such data is discussed."}
{"id": "PMID:190001", "title": "Terminal nucleotide sequences of 17-S ribosomal RNA and its immediate precursor 18-S RNA in yeast.", "content": "The 5' and 3'-terminal nucleotide sequences of 17-S rRNA and its immediate precursor 18-S RNA from the yeast Saccharomyces carlsbergensis have been analysed. Identification of the terminal oligonucleotides, as present in Ti ribonuclease digests, was performed by diagonal procedures. The major (molar yield 0.9) 5'-terminal oligonucleotide (molar yield 0.15) with the overall composition pU (U2,C2)G was observed. 18-S precursor RNA was found to contain the same 5'-terminal sequences as 17-S rRNA. However, the 3'-terminal sequences of the two types of RNA appeared to be different. The 17-S rRNA yields the oligonucleotide A-U-C-A-U-U-AOH while at least half of the 18-S RNA molecules contain the sequence U-U-U-C-A-A-U-AOH. In addition 18-S RNA yields several minor 3'-terminal oligonucleotides which appear to be structurally related to the major 3'-terminal sequence. These results demonstrate that the extra nucleotides in 18-S RNA relative to 17-S RNA are located exclusively at the 3'-terminus of the 18-S RNA molecule. The possibility that the 3'-terminal nucleotide sequence of 18-S RNA plays a role in the maturation process is discussed.", "contents": "Terminal nucleotide sequences of 17-S ribosomal RNA and its immediate precursor 18-S RNA in yeast. The 5' and 3'-terminal nucleotide sequences of 17-S rRNA and its immediate precursor 18-S RNA from the yeast Saccharomyces carlsbergensis have been analysed. Identification of the terminal oligonucleotides, as present in Ti ribonuclease digests, was performed by diagonal procedures. The major (molar yield 0.9) 5'-terminal oligonucleotide (molar yield 0.15) with the overall composition pU (U2,C2)G was observed. 18-S precursor RNA was found to contain the same 5'-terminal sequences as 17-S rRNA. However, the 3'-terminal sequences of the two types of RNA appeared to be different. The 17-S rRNA yields the oligonucleotide A-U-C-A-U-U-AOH while at least half of the 18-S RNA molecules contain the sequence U-U-U-C-A-A-U-AOH. In addition 18-S RNA yields several minor 3'-terminal oligonucleotides which appear to be structurally related to the major 3'-terminal sequence. These results demonstrate that the extra nucleotides in 18-S RNA relative to 17-S RNA are located exclusively at the 3'-terminus of the 18-S RNA molecule. The possibility that the 3'-terminal nucleotide sequence of 18-S RNA plays a role in the maturation process is discussed."}
{"id": "PMID:190002", "title": "2'-Deoxy-2'-azidocytidine, a new inhibitor of DNA replication in mammalian cells.", "content": "Cell growth is reversibly inhibited by the nucleoside analogue, 2'-deoxy-2'-azidocytidine and the inhibition is a result of interference with DNA replication. The 5'-diphosphate of the analogue was earlier shown to specifically inactivate the enzyme ribonucleotide reductase in vitro. However, measurements of the pools of deoxyribonucleoside triphosphates in cells incubated in azidocytidine showed only minor changes which appeared to result from and not to be the cause of the inhibition of DNA replication. The DNA synthesized in polyoma-infected cells after incubation in azidocytidine showed a sedimentation pattern quite different from that seen after inhibition of DNA synthesis with arabinosyl cytosine or hydroxyurea. Experiments with nuclei isolated from azidocytidine-inhibited, polyoma-infected cells indicated (a) that the number of replicating molecules is decreased during the inhibition and (b) that upon incubation of the nuclei there is a rapid synthesis of DNA occurring in a new class of DNA molecules which are at a very early state of replication. Neither the 5'-triphosphate of azidocytidine nor the nucleoside itself inhibit DNA synthesis in vitro in isolated nuclei from polyoma-infected cells and at present the nature of the DNA-synthesis-inhibiting compound acting in the cells after addition of azidocytidine is unknown. Taken together the results suggest that azidocytidine inhibits DNA synthesis at an early stage, possible by blocking the initiation of DNA synthesis at the origin or by interfering with the elongation of newly initiated DNA molecules.", "contents": "2'-Deoxy-2'-azidocytidine, a new inhibitor of DNA replication in mammalian cells. Cell growth is reversibly inhibited by the nucleoside analogue, 2'-deoxy-2'-azidocytidine and the inhibition is a result of interference with DNA replication. The 5'-diphosphate of the analogue was earlier shown to specifically inactivate the enzyme ribonucleotide reductase in vitro. However, measurements of the pools of deoxyribonucleoside triphosphates in cells incubated in azidocytidine showed only minor changes which appeared to result from and not to be the cause of the inhibition of DNA replication. The DNA synthesized in polyoma-infected cells after incubation in azidocytidine showed a sedimentation pattern quite different from that seen after inhibition of DNA synthesis with arabinosyl cytosine or hydroxyurea. Experiments with nuclei isolated from azidocytidine-inhibited, polyoma-infected cells indicated (a) that the number of replicating molecules is decreased during the inhibition and (b) that upon incubation of the nuclei there is a rapid synthesis of DNA occurring in a new class of DNA molecules which are at a very early state of replication. Neither the 5'-triphosphate of azidocytidine nor the nucleoside itself inhibit DNA synthesis in vitro in isolated nuclei from polyoma-infected cells and at present the nature of the DNA-synthesis-inhibiting compound acting in the cells after addition of azidocytidine is unknown. Taken together the results suggest that azidocytidine inhibits DNA synthesis at an early stage, possible by blocking the initiation of DNA synthesis at the origin or by interfering with the elongation of newly initiated DNA molecules."}
{"id": "PMID:190003", "title": "The synthesis of macromolecular 3-hydroxyproline by attaching and confluent cultures of human fibroblasts.", "content": "The synthesis of collagen has been studied during the attachment of freshly trypsinized human fibroblasts to culture vessels by measurement of the incorporation of radioactive proline into macromolecular hydroxyproline. Collagenous protein(s) was found to be a component of a substrate-attached material ('microexudate carpet') synthesized rapidly during cell attachment in the absence of serum. The ratio of 3-hydroxyproline/4-hydroxyproline in the collagenous proteins synthesized during cell attachment was found to be 4-5 fold higher than that of normal type I collagen. The synthesis of 3-hydroxyproline by confluent cultures was diminished by serum deprivation, and was shown to require higher concentrations of ascorbate than the synthesis of the 4-hydroxy isomer.", "contents": "The synthesis of macromolecular 3-hydroxyproline by attaching and confluent cultures of human fibroblasts. The synthesis of collagen has been studied during the attachment of freshly trypsinized human fibroblasts to culture vessels by measurement of the incorporation of radioactive proline into macromolecular hydroxyproline. Collagenous protein(s) was found to be a component of a substrate-attached material ('microexudate carpet') synthesized rapidly during cell attachment in the absence of serum. The ratio of 3-hydroxyproline/4-hydroxyproline in the collagenous proteins synthesized during cell attachment was found to be 4-5 fold higher than that of normal type I collagen. The synthesis of 3-hydroxyproline by confluent cultures was diminished by serum deprivation, and was shown to require higher concentrations of ascorbate than the synthesis of the 4-hydroxy isomer."}
{"id": "PMID:190004", "title": "Purification of bovine adrenal-cortex plasma-membrane vesicles containing a highly corticotropin-sensitive adenylate-cyclase system and angiotensin-II-binding sites.", "content": "The purpose of this experimental investigation was to provide a purified plasma membrane fraction containing a highly hormone-responsive adenylate cyclase system. Bovine adrenal cortex was homogenised and a washed pellet (450 000 X g - min) was fractionated by zonal centrifugation in a sucrose and dextran gradient. Adenylate cyclase activity was purified up to 60-fold to a specific activity of 55, 340 and 210 pmol of adenosine 3':5'-monophosphate (cyclic AMP) produced/minute per mg of protein at 38 degrees C for the basal, adrenocorticotrophin and fluoride-activated states, respectively. The time course of the adenylate cyclase activity is linear. The concentration necessary for half-maximal stimulation by adrenocorticotrophin-(1-24)-tetracosipeptide is 0.5 muM. The high hormone-responsiveness of the membrane preparation allows one to demonstrate activation of adenylate cyclase by very weakly agonistic adrenocorticotrophin fragments. The F- activated state can be detergent-dispersed by Lubrol and shows a Km (ATP) different from that of either the basal or adrenocorticotrophin-stimulated state. Other marked enzymes such as 5'-nucleotidase, glucose-6-phosphatase and cytochrome oxidase were followed during purification. The plasma membrane fraction shows rather homogeneous, relatively large vesicles (mean diameter 0.5 mum). It contains high-affinity binding sites for angiotensin II (about 2 pmol per mg protein) with an apparent association constant of 2 X 10(7) (1/mol) at 12 degrees C. The yield, 20 mg of membrane protein per preparation, may make it a tool in either affinity-labelling studies with the peptide hormones mentioned or the starting point for solubilisation and purification of adenylate cyclase.", "contents": "Purification of bovine adrenal-cortex plasma-membrane vesicles containing a highly corticotropin-sensitive adenylate-cyclase system and angiotensin-II-binding sites. The purpose of this experimental investigation was to provide a purified plasma membrane fraction containing a highly hormone-responsive adenylate cyclase system. Bovine adrenal cortex was homogenised and a washed pellet (450 000 X g - min) was fractionated by zonal centrifugation in a sucrose and dextran gradient. Adenylate cyclase activity was purified up to 60-fold to a specific activity of 55, 340 and 210 pmol of adenosine 3':5'-monophosphate (cyclic AMP) produced/minute per mg of protein at 38 degrees C for the basal, adrenocorticotrophin and fluoride-activated states, respectively. The time course of the adenylate cyclase activity is linear. The concentration necessary for half-maximal stimulation by adrenocorticotrophin-(1-24)-tetracosipeptide is 0.5 muM. The high hormone-responsiveness of the membrane preparation allows one to demonstrate activation of adenylate cyclase by very weakly agonistic adrenocorticotrophin fragments. The F- activated state can be detergent-dispersed by Lubrol and shows a Km (ATP) different from that of either the basal or adrenocorticotrophin-stimulated state. Other marked enzymes such as 5'-nucleotidase, glucose-6-phosphatase and cytochrome oxidase were followed during purification. The plasma membrane fraction shows rather homogeneous, relatively large vesicles (mean diameter 0.5 mum). It contains high-affinity binding sites for angiotensin II (about 2 pmol per mg protein) with an apparent association constant of 2 X 10(7) (1/mol) at 12 degrees C. The yield, 20 mg of membrane protein per preparation, may make it a tool in either affinity-labelling studies with the peptide hormones mentioned or the starting point for solubilisation and purification of adenylate cyclase."}
{"id": "PMID:190005", "title": "Purification and properties of a periplasmic protein related to sn-glycerol-3-phosphate transport in Escherichia coli.", "content": "Protein GLPT, a periplasmic protein previously recognized as closely related to the active transport of sn-glycerol-3-phosphate in Escherichia coli was isolated by the cold osmotic shock procedure. It was purified by Sephadex chromatography and isoelectric focussing. The purified protein does not exhibit any detectable binding activity toward sn-glycerol-3-phosphate. It has no activity as a glycerol phosphatase nor as a glycerol kinase. Polyacrylamide gel electrophoresis in the presence of dodecylsulfate of the protein subsequent to treatment in urea, boiling in dodecylsulfate and crosslinking indicates that it occurs as an oligomeric protein composed of four identical subunits of 40 000 molecular weight. Membrane vesicles of wild-type strains that contain protein GLPT in whole cells loose it during vesicle preparation. However, they still exhibit high transport activity toward sn-glycerol-3-phosphate. Membrane vesicles prepared from glp T mutants that may or may not contain protein GLPT do not transport sn-glycerol-3-phospahte. We conclude from these results that protein GLPT does not participate in the energy-dependent active transport through the cytoplasmic membrane but could be involved in facilitating the diffusion of sn-glycerol-3-phosphate through the outer layers of E. coli.", "contents": "Purification and properties of a periplasmic protein related to sn-glycerol-3-phosphate transport in Escherichia coli. Protein GLPT, a periplasmic protein previously recognized as closely related to the active transport of sn-glycerol-3-phosphate in Escherichia coli was isolated by the cold osmotic shock procedure. It was purified by Sephadex chromatography and isoelectric focussing. The purified protein does not exhibit any detectable binding activity toward sn-glycerol-3-phosphate. It has no activity as a glycerol phosphatase nor as a glycerol kinase. Polyacrylamide gel electrophoresis in the presence of dodecylsulfate of the protein subsequent to treatment in urea, boiling in dodecylsulfate and crosslinking indicates that it occurs as an oligomeric protein composed of four identical subunits of 40 000 molecular weight. Membrane vesicles of wild-type strains that contain protein GLPT in whole cells loose it during vesicle preparation. However, they still exhibit high transport activity toward sn-glycerol-3-phosphate. Membrane vesicles prepared from glp T mutants that may or may not contain protein GLPT do not transport sn-glycerol-3-phospahte. We conclude from these results that protein GLPT does not participate in the energy-dependent active transport through the cytoplasmic membrane but could be involved in facilitating the diffusion of sn-glycerol-3-phosphate through the outer layers of E. coli."}
{"id": "PMID:190006", "title": "The roles of c-type cytochromes in algal photosynthesis. Extraction from algae of a cytochrome similar to higher plant cytochrome f.", "content": "A membrane-bound cytochrome resembling higher plant cytochrome f in many respects has been extracted from the algae Chlamydomonas. Euglena and Anacystis, and partially purified. The spectra of the cytochromes from Chlamydomonas and Euglena are virtually identical to that of parsley cytochrome f, with alpha-band maxima near 554 nm, very asymmetrical beta-bands, and gamma-band maxima at 421 nm. The cytochrome from Anacystis had alpha and gamma-bands both shifted to slightly longer wavelengths. The redox potential of the cytochrome from Chlamydomonas was determined as +350 mV, and its minimum molecular weight in sodium dodecyl sulphate as 31 000. The cytochrome from Euglena showed a rate of reaction with higher plant plastocyanin at least 100 times that of the soluble Euglena cytochrome c-552, and was unaffected by Euglena cytochrome c-552 antiserum. A very fast rate of electron transfer occurred between this cytochrome purified from Euglena and cytochrome c-552. The roles of the membrane-bound and soluble c-type cytochromes in algal photosynthesis are discussed, and it is recommended that the name cytochrome f should be reserved for the membrane-bound cytochrome (to emphasize its affinity with higher plant cytochrome f), while the soluble one should be named by its alpha-band (c-552, c-553, etc.) to make clear its distinctness from higher plant cytochrome f and homology with mitochondrial cytochrome c.", "contents": "The roles of c-type cytochromes in algal photosynthesis. Extraction from algae of a cytochrome similar to higher plant cytochrome f. A membrane-bound cytochrome resembling higher plant cytochrome f in many respects has been extracted from the algae Chlamydomonas. Euglena and Anacystis, and partially purified. The spectra of the cytochromes from Chlamydomonas and Euglena are virtually identical to that of parsley cytochrome f, with alpha-band maxima near 554 nm, very asymmetrical beta-bands, and gamma-band maxima at 421 nm. The cytochrome from Anacystis had alpha and gamma-bands both shifted to slightly longer wavelengths. The redox potential of the cytochrome from Chlamydomonas was determined as +350 mV, and its minimum molecular weight in sodium dodecyl sulphate as 31 000. The cytochrome from Euglena showed a rate of reaction with higher plant plastocyanin at least 100 times that of the soluble Euglena cytochrome c-552, and was unaffected by Euglena cytochrome c-552 antiserum. A very fast rate of electron transfer occurred between this cytochrome purified from Euglena and cytochrome c-552. The roles of the membrane-bound and soluble c-type cytochromes in algal photosynthesis are discussed, and it is recommended that the name cytochrome f should be reserved for the membrane-bound cytochrome (to emphasize its affinity with higher plant cytochrome f), while the soluble one should be named by its alpha-band (c-552, c-553, etc.) to make clear its distinctness from higher plant cytochrome f and homology with mitochondrial cytochrome c."}
{"id": "PMID:190007", "title": "The binding of carbon monoxide to cytochrome c oxidase.", "content": "The effect of CO on the optical absorbance spectrum of partially reduced cytochrome c oxidase  has been studied. The changes at 432 and 590 nm suggest that the cytochrome alpha2/3+ - CO compound is formed preferentially and that concomitantly a second electron is taken up by the enzyme. From the CO-induced changes at 830 nm it is concluded that in the partially reduced enzyme addition of CO causes reoxidation of the copper component of cytochrome c oxidase. Addition of CO to partially reduced enzyme (2 electrons per 4 metal ions) also brings about a decrease in the intensities of electron paramagnetic resonance signals of high-spin heme iron near g = 6 and of the low-spin heme at g = 2.6. Concomitantly both the low-spin heme a signal at g = 3 and the copper signal at g = 2 increase in intensity. These results demonstrate that formation of the reduced diamagnetic cytochrome a3 - CO compound is accompanied by reoxidation of both the copper component detectable by electron paramagnetic resonance and possibly also by cytochrome a.", "contents": "The binding of carbon monoxide to cytochrome c oxidase. The effect of CO on the optical absorbance spectrum of partially reduced cytochrome c oxidase  has been studied. The changes at 432 and 590 nm suggest that the cytochrome alpha2/3+ - CO compound is formed preferentially and that concomitantly a second electron is taken up by the enzyme. From the CO-induced changes at 830 nm it is concluded that in the partially reduced enzyme addition of CO causes reoxidation of the copper component of cytochrome c oxidase. Addition of CO to partially reduced enzyme (2 electrons per 4 metal ions) also brings about a decrease in the intensities of electron paramagnetic resonance signals of high-spin heme iron near g = 6 and of the low-spin heme at g = 2.6. Concomitantly both the low-spin heme a signal at g = 3 and the copper signal at g = 2 increase in intensity. These results demonstrate that formation of the reduced diamagnetic cytochrome a3 - CO compound is accompanied by reoxidation of both the copper component detectable by electron paramagnetic resonance and possibly also by cytochrome a."}
{"id": "PMID:190008", "title": "Evidence for the identity of nuclear and cytoplasmic adenosine-3':5'-monophosphate-dependent protein kinase from porcine ovaries and nuclear translocation of the cytoplasmic enzyme.", "content": "Protein phosphokinase activity from a 0.5 M NaCl extract of purified porcine ovary nuclei has been resolved by Sephadex G-200 gel filtration into three forms of kinase, protein kinase I and III, both independent of adenosine 3':5'-monophosphate (cyclic AMP), and cyclic-AMP-dependent protein kinase II. Cyclic AMP-binding activity was associated with protein kinase II but not with protein kinases I and III. Protein kinases I, II, and III exhibited different cyclic nucleotide dependency and substrate specificity. Protein kinase II was inhibited by a heat-stable protein from rabbit skeletal muscle, whereas protein kinases I and III were not inhibited. According to previously established criteria [Traugh, J.A., Ashby, C.D. and Walsh, D.A. (1974) nuclear protein kinase II can be classified as cyclic-AMP-dependent protein kinase consisting of regulatory and catalytic subunits. Nuclear protein kinases I and III are cyclic-AMP-independent enzymes. Evidence for the identity of nuclear cyclic-AMP-dependent protein kinase II with cytosol (105 000 X g supernatant fraction) cyclic-AMP-dependent protein kinase was obtained in several ways. Nuclear and cytosol cyclic-AMP-dependent protein kinases exhibited identical elution characteristics on DEAE-cellulose and Sephadex G-200 indicating that both kinases are of similar molecular size and possess similar ionic charge. Both kinases exhibited an identical Km for ATP of 8 muM, showed similar substrate specificity, and revealed similar antigenic properties. Cyclic-AMP-dependent protein kinase II was also identified in nuclei isolated in nonaqueous media, eliminating the possibility that the cyclic-AMP-dependent protein kinase activity identified in nuclei isolated in aqueous media may have arisen as the result of cytoplasmic contamination. After incubation of neonatal porcine ovaries which lack nuclear cyclic-AMP-dependent protein kinase with 0.1 muM 8-p-chlorophenylthio cyclic AMP, considerable cyclic-AMP-dependent protein kinase II activity was identified in nuclei isolated in nonaqueous media. From these data it is concluded that the nuclear cyclic-AMP-dependent protein kinase II is related to or identical with the ovary cytoplasmic cyclic-AMP-dependent protein kinase, supporting the concept that nuclear cyclic-AMP-dependent protein kinase is of cytoplasmic origin.", "contents": "Evidence for the identity of nuclear and cytoplasmic adenosine-3':5'-monophosphate-dependent protein kinase from porcine ovaries and nuclear translocation of the cytoplasmic enzyme. Protein phosphokinase activity from a 0.5 M NaCl extract of purified porcine ovary nuclei has been resolved by Sephadex G-200 gel filtration into three forms of kinase, protein kinase I and III, both independent of adenosine 3':5'-monophosphate (cyclic AMP), and cyclic-AMP-dependent protein kinase II. Cyclic AMP-binding activity was associated with protein kinase II but not with protein kinases I and III. Protein kinases I, II, and III exhibited different cyclic nucleotide dependency and substrate specificity. Protein kinase II was inhibited by a heat-stable protein from rabbit skeletal muscle, whereas protein kinases I and III were not inhibited. According to previously established criteria [Traugh, J.A., Ashby, C.D. and Walsh, D.A. (1974) nuclear protein kinase II can be classified as cyclic-AMP-dependent protein kinase consisting of regulatory and catalytic subunits. Nuclear protein kinases I and III are cyclic-AMP-independent enzymes. Evidence for the identity of nuclear cyclic-AMP-dependent protein kinase II with cytosol (105 000 X g supernatant fraction) cyclic-AMP-dependent protein kinase was obtained in several ways. Nuclear and cytosol cyclic-AMP-dependent protein kinases exhibited identical elution characteristics on DEAE-cellulose and Sephadex G-200 indicating that both kinases are of similar molecular size and possess similar ionic charge. Both kinases exhibited an identical Km for ATP of 8 muM, showed similar substrate specificity, and revealed similar antigenic properties. Cyclic-AMP-dependent protein kinase II was also identified in nuclei isolated in nonaqueous media, eliminating the possibility that the cyclic-AMP-dependent protein kinase activity identified in nuclei isolated in aqueous media may have arisen as the result of cytoplasmic contamination. After incubation of neonatal porcine ovaries which lack nuclear cyclic-AMP-dependent protein kinase with 0.1 muM 8-p-chlorophenylthio cyclic AMP, considerable cyclic-AMP-dependent protein kinase II activity was identified in nuclei isolated in nonaqueous media. From these data it is concluded that the nuclear cyclic-AMP-dependent protein kinase II is related to or identical with the ovary cytoplasmic cyclic-AMP-dependent protein kinase, supporting the concept that nuclear cyclic-AMP-dependent protein kinase is of cytoplasmic origin."}
{"id": "PMID:190009", "title": "Different types of mitochondria in parenchymal and non-parenchymal rat-liver cells.", "content": "1. Intact and pure parenchymal and non-parenchymal cells were isolated from rat liver. The specific activities of several mitochondrial enzymes were determined in both parenchymal and  non-parenchymal cell homogenates to characterize the mitochondria in these liver cell types. 2. In general the activities of mitochondrial enzymes were lower in non-parenchymal liver cells than in parenchymal cells. The specific activity of pyruvate carboxylase in non-parenchymal cells expressed as the percentage of that in parenchymal cells was onlu 2% for glutamate dehydrogenase 4.3% and for cytochrome c oxidase 79.4%. Monoamine oxidase, as an exception, has an equal specific activity in both cell types. 3. The activity ratio of pyruvate carboxylase at 10 mM pyruvate over 0.1 mM pyruvate is 3.35 for parenchymal cells and 1.50 for non-parenchymal cells. This indicates that non-parenchymal liver cells only contain the high affinity form of pyruvate carboxylase in contrast to parenchymal cells. 4. The ratio of glycerol-3-phosphate cytochrome c reductase over succinate cytochrome c reductase activity differs from parenchymal (0.01) and non-parenchymal cells (0.10). This might indicate that the glycerol-3-phosphate shuttle, which is important for the transport of reduction equivalents for cytosol to mitochondria is relatively more active in non-parenchymal cells than in parenchymal cells. 5. The activity pattern of mitochondrial enzymes in parenchymal and non-parenchymal cell homogenates indicates that these cell types contain different types of mitochondria. The presence of these different cell types in liver will therefore contribute to the heterogeneity of isolated rat liver mitochondria in which the mitochondria from non-parenchymal cells might be considered as \"non-gluconeogenic\".", "contents": "Different types of mitochondria in parenchymal and non-parenchymal rat-liver cells. 1. Intact and pure parenchymal and non-parenchymal cells were isolated from rat liver. The specific activities of several mitochondrial enzymes were determined in both parenchymal and  non-parenchymal cell homogenates to characterize the mitochondria in these liver cell types. 2. In general the activities of mitochondrial enzymes were lower in non-parenchymal liver cells than in parenchymal cells. The specific activity of pyruvate carboxylase in non-parenchymal cells expressed as the percentage of that in parenchymal cells was onlu 2% for glutamate dehydrogenase 4.3% and for cytochrome c oxidase 79.4%. Monoamine oxidase, as an exception, has an equal specific activity in both cell types. 3. The activity ratio of pyruvate carboxylase at 10 mM pyruvate over 0.1 mM pyruvate is 3.35 for parenchymal cells and 1.50 for non-parenchymal cells. This indicates that non-parenchymal liver cells only contain the high affinity form of pyruvate carboxylase in contrast to parenchymal cells. 4. The ratio of glycerol-3-phosphate cytochrome c reductase over succinate cytochrome c reductase activity differs from parenchymal (0.01) and non-parenchymal cells (0.10). This might indicate that the glycerol-3-phosphate shuttle, which is important for the transport of reduction equivalents for cytosol to mitochondria is relatively more active in non-parenchymal cells than in parenchymal cells. 5. The activity pattern of mitochondrial enzymes in parenchymal and non-parenchymal cell homogenates indicates that these cell types contain different types of mitochondria. The presence of these different cell types in liver will therefore contribute to the heterogeneity of isolated rat liver mitochondria in which the mitochondria from non-parenchymal cells might be considered as \"non-gluconeogenic\"."}
{"id": "PMID:190010", "title": "Effect of hyperoxide radicals on bovine-erythrocyte membrane.", "content": "1. Bovine erythrocytes exposed to the action of an enzymic source of hyperoxide radicals (hypoxanthine + xanthine oxidase) exhibited hemolysis, which was prevented by the presence of hyperoxide dismutase. 2. Exposing bovine erythrocyte membranes to the source of hyperoxide radicals resulted in a decrease of (Mg2+ + Na+ + K+)ATPase activity which could be partially prevented by addition of hyperoxide dismutase. 3. The damage observed to erythrocyte membranes under the conditions applied is ascribed to toh formed in the Haber and Weiss reaction since a protection by OH scavengers was also observed.", "contents": "Effect of hyperoxide radicals on bovine-erythrocyte membrane. 1. Bovine erythrocytes exposed to the action of an enzymic source of hyperoxide radicals (hypoxanthine + xanthine oxidase) exhibited hemolysis, which was prevented by the presence of hyperoxide dismutase. 2. Exposing bovine erythrocyte membranes to the source of hyperoxide radicals resulted in a decrease of (Mg2+ + Na+ + K+)ATPase activity which could be partially prevented by addition of hyperoxide dismutase. 3. The damage observed to erythrocyte membranes under the conditions applied is ascribed to toh formed in the Haber and Weiss reaction since a protection by OH scavengers was also observed."}
{"id": "PMID:190011", "title": "Cyclic nucleotide phosphodiesterases from rat anterior pituitary. Characterization of multiple forms and regulation by protein activator and Ca+.", "content": "Phosphodiesterase activities for adenosine and guanosine 3':5'-monophosphates (cyclic AMP and cyclic GMP) were demonstrated in particulate and soluble fractions of rat anterior pituitary gland. Both fractions contained higher activity for cyclic GMP hydrolysis than that for cyclic AMP hydrolysis when these activities were assayed at subsaturating substrate concentrations. Addition of protein activator and CaCl2 to either whole homogenate, particulate or supernatant fraction stimulated both cyclic AMP and cyclic GMP phosphadiesterase activities. Almost 80% of cyclic AMP and 90% of cyclic GMP hydrolyzing activities were localized in soluble fraction. Particulate-bound cyclic nucleotide phosphodiesterase activity was completely solubilized with 1% Triton X-100. Detergent-dispersed particulate and soluble enzymes were compared with respect to Ca2+ and activator requirements and gel filtration profiles. Particulate, soluble and partially purified phosphodiesterase activities were also characterized in relation to divalent cation requirements, kinetic behavior and effects of Ca2+, activator and ethyleneglycol-bis-(2-aminoethyl)-N,N'-tetraacetic acid. Gel filtration of either sonicated whole homogenate or the 10500 X g supernatant fraction showed a single peak of activity, which hydrolyzed both cyclic AMP and cyclic GMP and was dependent upon Ca2+ and activator for maximum activity. Partially purified enzyme was inhibited by 1-methyl-3-isobutylxanthine and papaverine with the concentration of inhibitor giving 50% inhibition at 0.4 muM substrate being 20 muM and 24 muM for cyclic AMP and 7 muM and 10 muM for cyclic GMP, respectively. Theophylline, caffeine and theobromine were less effective. The rat anterior pituitary also contained a protein activator which stimulated both pituitary cyclic nucleotide phosphodiesterase(s) as well as activator-deficient brain cyclic GMP and cyclic AMP phosphodiesterases. Chromatography of the sonicated pituitary extract on DEAE-cellulose column chromatography resolved the phosphodiesterase into two fractions. Both enzyme fractions hydrolyzed cyclic AMP and cyclic GMP and had comparable apparent Km values for the two nucleotides. Hydrolysis of cyclic GMP and cyclic AMP by fraction II enzyme was stimulated 6--7-fold by both pituitary and brain activator in the presence of micromolar concentrations of Ca2+.", "contents": "Cyclic nucleotide phosphodiesterases from rat anterior pituitary. Characterization of multiple forms and regulation by protein activator and Ca+. Phosphodiesterase activities for adenosine and guanosine 3':5'-monophosphates (cyclic AMP and cyclic GMP) were demonstrated in particulate and soluble fractions of rat anterior pituitary gland. Both fractions contained higher activity for cyclic GMP hydrolysis than that for cyclic AMP hydrolysis when these activities were assayed at subsaturating substrate concentrations. Addition of protein activator and CaCl2 to either whole homogenate, particulate or supernatant fraction stimulated both cyclic AMP and cyclic GMP phosphadiesterase activities. Almost 80% of cyclic AMP and 90% of cyclic GMP hydrolyzing activities were localized in soluble fraction. Particulate-bound cyclic nucleotide phosphodiesterase activity was completely solubilized with 1% Triton X-100. Detergent-dispersed particulate and soluble enzymes were compared with respect to Ca2+ and activator requirements and gel filtration profiles. Particulate, soluble and partially purified phosphodiesterase activities were also characterized in relation to divalent cation requirements, kinetic behavior and effects of Ca2+, activator and ethyleneglycol-bis-(2-aminoethyl)-N,N'-tetraacetic acid. Gel filtration of either sonicated whole homogenate or the 10500 X g supernatant fraction showed a single peak of activity, which hydrolyzed both cyclic AMP and cyclic GMP and was dependent upon Ca2+ and activator for maximum activity. Partially purified enzyme was inhibited by 1-methyl-3-isobutylxanthine and papaverine with the concentration of inhibitor giving 50% inhibition at 0.4 muM substrate being 20 muM and 24 muM for cyclic AMP and 7 muM and 10 muM for cyclic GMP, respectively. Theophylline, caffeine and theobromine were less effective. The rat anterior pituitary also contained a protein activator which stimulated both pituitary cyclic nucleotide phosphodiesterase(s) as well as activator-deficient brain cyclic GMP and cyclic AMP phosphodiesterases. Chromatography of the sonicated pituitary extract on DEAE-cellulose column chromatography resolved the phosphodiesterase into two fractions. Both enzyme fractions hydrolyzed cyclic AMP and cyclic GMP and had comparable apparent Km values for the two nucleotides. Hydrolysis of cyclic GMP and cyclic AMP by fraction II enzyme was stimulated 6--7-fold by both pituitary and brain activator in the presence of micromolar concentrations of Ca2+."}
{"id": "PMID:190012", "title": "2-Deoxy-D-galactose metabolism in ascites hepatoma cells results in phosphate trapping and glycolysis inhibition.", "content": "The metabolism of 2-deoxy-D-galactose has been studied in AS-30D rat ascites hepatoma cells in suspension. Using 2-deoxy-D-(1-14C)galactose and an alkaline ethanol deproteinization procedure, the quantitatively identified metabolites included 2-deoxy-D-galactose 1-phosphate comprising 99.3%, and UDP-2-deoxy-D-galactose and UDP-2-deoxy-D-glucose, together amounting to 0.4% of the total metabolites. After incubation for 5 h in the presence of 2-deoxy-D-galactose (1 mmo1/1), the content of 2-deoxy-D-galactose 1-phosphate reached 35 mmo1x(kg cells)-1. The rate of phosphorylation of 2-deoxy-D-galactose was rapid during the first 30 min and decreased to approximately 20% of this rate during the subsequent hours. The rapid trapping of Pi in the form of 2-deoxy-D-galactose 1-phosphate resulted in a depression of free intracellular Pi in spite of a concomitant increase in net 32Pi uptake from the medium and a decrease of ATP and other 5'-nucleotides. The rates of glucose utilization and lactate production were depressed by more than 80% in the presence of 2-deoxy-D-galactose (1 mmo1/1). Interruption of Pi trapping by removal of 2-deoxy-D-galactose from the medium reversed the depressions of Pi and ATP and resulted in a rapid but incomplete relief of glycolysis inhibition. Crossover analysis of glycolytic intermediates indicated an inhibition at the 6-phosphofructokinase step. The depression of glucose utilization may be mediated by the increased level of glucose 6-phosphate, a potent inhibitor of hexokinase. An additional inhibitory effect of a metabolite of 2-deoxy-D-galactose at the 6-phosphofructokinase step was indicated by crossover analysis after reversal of Pi and ATP depressions in the presence of a high intracellular content of 2-deoxy-D-glactose 1-phosphate. The quantitative analysis of the metabolites of 2-deoxy-D-galactose demonstrated the predominance of the monophosphate and the negligible formation of UPD derivatives of this sugar analog in AS-30D hepatoma cells. This provides a system for the investigation of a galactose analog as a phosphate-trapping agent in the virtual absence of uridylate trapping.", "contents": "2-Deoxy-D-galactose metabolism in ascites hepatoma cells results in phosphate trapping and glycolysis inhibition. The metabolism of 2-deoxy-D-galactose has been studied in AS-30D rat ascites hepatoma cells in suspension. Using 2-deoxy-D-(1-14C)galactose and an alkaline ethanol deproteinization procedure, the quantitatively identified metabolites included 2-deoxy-D-galactose 1-phosphate comprising 99.3%, and UDP-2-deoxy-D-galactose and UDP-2-deoxy-D-glucose, together amounting to 0.4% of the total metabolites. After incubation for 5 h in the presence of 2-deoxy-D-galactose (1 mmo1/1), the content of 2-deoxy-D-galactose 1-phosphate reached 35 mmo1x(kg cells)-1. The rate of phosphorylation of 2-deoxy-D-galactose was rapid during the first 30 min and decreased to approximately 20% of this rate during the subsequent hours. The rapid trapping of Pi in the form of 2-deoxy-D-galactose 1-phosphate resulted in a depression of free intracellular Pi in spite of a concomitant increase in net 32Pi uptake from the medium and a decrease of ATP and other 5'-nucleotides. The rates of glucose utilization and lactate production were depressed by more than 80% in the presence of 2-deoxy-D-galactose (1 mmo1/1). Interruption of Pi trapping by removal of 2-deoxy-D-galactose from the medium reversed the depressions of Pi and ATP and resulted in a rapid but incomplete relief of glycolysis inhibition. Crossover analysis of glycolytic intermediates indicated an inhibition at the 6-phosphofructokinase step. The depression of glucose utilization may be mediated by the increased level of glucose 6-phosphate, a potent inhibitor of hexokinase. An additional inhibitory effect of a metabolite of 2-deoxy-D-galactose at the 6-phosphofructokinase step was indicated by crossover analysis after reversal of Pi and ATP depressions in the presence of a high intracellular content of 2-deoxy-D-glactose 1-phosphate. The quantitative analysis of the metabolites of 2-deoxy-D-galactose demonstrated the predominance of the monophosphate and the negligible formation of UPD derivatives of this sugar analog in AS-30D hepatoma cells. This provides a system for the investigation of a galactose analog as a phosphate-trapping agent in the virtual absence of uridylate trapping."}
{"id": "PMID:190013", "title": "Radiochemical purity of various 99mTc-labelled bone-scanning agents.", "content": "The radiochemical purity of preparations for 99mTc-bone-scanning was tested using thin-layer chromatography and electrophoresis. The investigation included ten commercial kits, comprising four types of phosphorus compounds, i.e. sodium polyphosphate, sodium pyrophosphate, disodium  diphosphonate, and sodium monofluorophosphate. Out-spoken differences in the content of free pertechnetate were found between the different kits. The contents in preparations from the same kit were fairly constant, but in some cases a change could be referred to the age of the 99mTc-generator or the time of analysis. No significant difference was found between preparations made from eluate with and without oxidizer. A 99mTc-tin-colloid was sporadically present in the preparations.", "contents": "Radiochemical purity of various 99mTc-labelled bone-scanning agents. The radiochemical purity of preparations for 99mTc-bone-scanning was tested using thin-layer chromatography and electrophoresis. The investigation included ten commercial kits, comprising four types of phosphorus compounds, i.e. sodium polyphosphate, sodium pyrophosphate, disodium  diphosphonate, and sodium monofluorophosphate. Out-spoken differences in the content of free pertechnetate were found between the different kits. The contents in preparations from the same kit were fairly constant, but in some cases a change could be referred to the age of the 99mTc-generator or the time of analysis. No significant difference was found between preparations made from eluate with and without oxidizer. A 99mTc-tin-colloid was sporadically present in the preparations."}
{"id": "PMID:190014", "title": "Adrenocorticotrophic hormone during the first day of life.", "content": "The plasma concentration of ACTH (by radioimmunoassay) was measured in 56 healthy parturients and their newborns. Umbilical cord and maternal venous blood were collected immediately after delivery. In addition one venous blood sample was taken from 50 newborns at the age of 15, 30, 60 min, 2, 6, 12, or 24 h. The maternal and cord plasma ACTH levels were higher than the levels in healthy nonpregnant women. There are no differences between the mean maternal (226 +/- 146 pg/ml) and cord (226 +/- 147 pg/ml) values of ACTH. The high ACTH levels of cord plasma remain unchanged for 30 min, decrease significantly during the 1-6 h after birth, because of the elimination process of the circulated foetal ACTH, and increase over the next 12-24 h and slightly thereafter indicating an initiation of neonatal pituitary ACTH secretion. The plasma ACTH level in the mothers with membranes ruptured for 1-5 h was significantly (P less than 0.05) higher compared with that in the mothers with membranes ruptured for less than 1 h. However, the duration of ruptured membranes appeared to have no effect on the cord blood ACTH level.", "contents": "Adrenocorticotrophic hormone during the first day of life. The plasma concentration of ACTH (by radioimmunoassay) was measured in 56 healthy parturients and their newborns. Umbilical cord and maternal venous blood were collected immediately after delivery. In addition one venous blood sample was taken from 50 newborns at the age of 15, 30, 60 min, 2, 6, 12, or 24 h. The maternal and cord plasma ACTH levels were higher than the levels in healthy nonpregnant women. There are no differences between the mean maternal (226 +/- 146 pg/ml) and cord (226 +/- 147 pg/ml) values of ACTH. The high ACTH levels of cord plasma remain unchanged for 30 min, decrease significantly during the 1-6 h after birth, because of the elimination process of the circulated foetal ACTH, and increase over the next 12-24 h and slightly thereafter indicating an initiation of neonatal pituitary ACTH secretion. The plasma ACTH level in the mothers with membranes ruptured for 1-5 h was significantly (P less than 0.05) higher compared with that in the mothers with membranes ruptured for less than 1 h. However, the duration of ruptured membranes appeared to have no effect on the cord blood ACTH level."}
{"id": "PMID:190015", "title": "Variations among individual mice in binding of growth hormone and insulin to membranes from animals of different ages.", "content": "Binding of 125I-labeled insulin and growth hormone to membranes from liver and hearts of C57BL/6J mice was measured and the data analyzed by the graphical method of Scatchard. Animals were studied at ages 2, 10, 20, and 31 months; preparations from each animal were analyzed individually. There was no significant and progressive age-related difference in either dissociation constant or binding capacity for insulin in heart and liver, or for growth hormone in liver. Variations among individual animals were large; in some cases, the standard deviation exceeded the mean for a particular age group. We conclude that there are no large age related differences in binding of these anabolic hormones to the target tissues studied, and that any small changes would be masked by the large variations among individual animals.", "contents": "Variations among individual mice in binding of growth hormone and insulin to membranes from animals of different ages. Binding of 125I-labeled insulin and growth hormone to membranes from liver and hearts of C57BL/6J mice was measured and the data analyzed by the graphical method of Scatchard. Animals were studied at ages 2, 10, 20, and 31 months; preparations from each animal were analyzed individually. There was no significant and progressive age-related difference in either dissociation constant or binding capacity for insulin in heart and liver, or for growth hormone in liver. Variations among individual animals were large; in some cases, the standard deviation exceeded the mean for a particular age group. We conclude that there are no large age related differences in binding of these anabolic hormones to the target tissues studied, and that any small changes would be masked by the large variations among individual animals."}
{"id": "PMID:190016", "title": "Morphine analgesia in mice of different ages.", "content": "The analgesic response to 5 mg per kg morphine sulfate was examined in male C57BL/6J mice aged from 2 months to 28 months by the tail-flick assay. The baseline latency of old mice was slightly lower than that of young mice. There was a smaller increase in latency after morphine in old mice than in young mice. Decreased analgesic response in old mice was accompanied by a slower rate of uptake of labeled morphine into the blood after i.p. injection and a longer half-life of the drug. There was no difference between young and old mice in the number of narcotic receptors in the brain.", "contents": "Morphine analgesia in mice of different ages. The analgesic response to 5 mg per kg morphine sulfate was examined in male C57BL/6J mice aged from 2 months to 28 months by the tail-flick assay. The baseline latency of old mice was slightly lower than that of young mice. There was a smaller increase in latency after morphine in old mice than in young mice. Decreased analgesic response in old mice was accompanied by a slower rate of uptake of labeled morphine into the blood after i.p. injection and a longer half-life of the drug. There was no difference between young and old mice in the number of narcotic receptors in the brain."}
{"id": "PMID:190027", "title": "Cholinergic transmission in subcortical and cortical visual centers of rats: no evidence for the involvement of primary optic system.", "content": "The effect of unilateral enucleation, ablation of the visual cortex or coagulation of the lateral geniculate nucleus (LGN) upon the activity of choline acetyltransferase (ChAc) and acetylcholinesterase (AChE) in different structures of the visual system of albino rats was studied. The localization and extent of the degeneration pattern were followed up by histological silver degeneration methods. Afferents from the retina project mainly contralaterally to the dorsal and ventral LGN, the pretectal region and the superior colliculus. Afferent fibres from the dorsal LGN enter the visual cortex in area 17 only. Neurons of this area project back ipsilaterally to the LGN and the superior colliculus (SC). No significant decrease in the activity of the cholinergic marker enzyme choline acetyltransferase could be observed under any of the experimental conditions; there was rather a tendency to increased activity in the subcortical centres. AChE as a less specific marker also exhibited no gross changes in activity in the lesioned animals. The results add more direct proof to pharmacological and physiological evidence that ACh is not involved in the synaptic transmission of the direct optic projections in rats, either at the subcortical or at the cortical level.", "contents": "Cholinergic transmission in subcortical and cortical visual centers of rats: no evidence for the involvement of primary optic system. The effect of unilateral enucleation, ablation of the visual cortex or coagulation of the lateral geniculate nucleus (LGN) upon the activity of choline acetyltransferase (ChAc) and acetylcholinesterase (AChE) in different structures of the visual system of albino rats was studied. The localization and extent of the degeneration pattern were followed up by histological silver degeneration methods. Afferents from the retina project mainly contralaterally to the dorsal and ventral LGN, the pretectal region and the superior colliculus. Afferent fibres from the dorsal LGN enter the visual cortex in area 17 only. Neurons of this area project back ipsilaterally to the LGN and the superior colliculus (SC). No significant decrease in the activity of the cholinergic marker enzyme choline acetyltransferase could be observed under any of the experimental conditions; there was rather a tendency to increased activity in the subcortical centres. AChE as a less specific marker also exhibited no gross changes in activity in the lesioned animals. The results add more direct proof to pharmacological and physiological evidence that ACh is not involved in the synaptic transmission of the direct optic projections in rats, either at the subcortical or at the cortical level."}
{"id": "PMID:190046", "title": "Use of 3H and 14C doubly labeled glucose and amino acids in the study of hormonal regulation of gluconeogenesis in rats.", "content": "Double isotope procedures (3H and 14C) were used in vivo to investigate a) slow long-term gluconeogenic actions of adrenal glucocorticoids, and b) rapid stimulation of gluconeogenesis by glucagon. [U-14C,6-3H]Glucose was administered to normal and adrenalectomized rats. No effect was observed on the [6-3H]glucose half-life suggesting the dicarboxylic acid shuttle is unaffected by adrenalectomy; the Cori cycle is also not influenced. Loads of [14C]aspartate, [14C]glutamate, or [14C]alanine were given to normal and adrenalectomized rats. Simultaneously, in vivo transaminase activity was studied by measuring the appearance of 3H2O in body water after administration of [2-3H]aspartate, [2-3H]glutamate, or [2-3H]alanine, Adrenalectomy has no influence on the incorporation of glutamate or aspartate into glucose or on their in vivo transaminases. Diminution of incorporation of [14C]alanine into glucose and alanine transaminase activities occurs only when rats are given unphysiological loads. These studies support the contention that glucocorticoid rate-limiting actions occur in extrahepatic tissues to produce an increased flow of glucose precursors to the liver. [U-14C,3-3H]Glucose was used to investigate the effect of glucagon on the hepatic fructose-6-phosphate (F-6-P) cycle. Glucagon administration resulted in a rapid drop in the 3H/14C ratio of circulating glucose, suggesting an increase in F-6-P recycling caused by activation of FDPase with little or no decrease in phosphofructokinase. Such a change would direct substrate flux toward gluconeogenesis.", "contents": "Use of 3H and 14C doubly labeled glucose and amino acids in the study of hormonal regulation of gluconeogenesis in rats. Double isotope procedures (3H and 14C) were used in vivo to investigate a) slow long-term gluconeogenic actions of adrenal glucocorticoids, and b) rapid stimulation of gluconeogenesis by glucagon. [U-14C,6-3H]Glucose was administered to normal and adrenalectomized rats. No effect was observed on the [6-3H]glucose half-life suggesting the dicarboxylic acid shuttle is unaffected by adrenalectomy; the Cori cycle is also not influenced. Loads of [14C]aspartate, [14C]glutamate, or [14C]alanine were given to normal and adrenalectomized rats. Simultaneously, in vivo transaminase activity was studied by measuring the appearance of 3H2O in body water after administration of [2-3H]aspartate, [2-3H]glutamate, or [2-3H]alanine, Adrenalectomy has no influence on the incorporation of glutamate or aspartate into glucose or on their in vivo transaminases. Diminution of incorporation of [14C]alanine into glucose and alanine transaminase activities occurs only when rats are given unphysiological loads. These studies support the contention that glucocorticoid rate-limiting actions occur in extrahepatic tissues to produce an increased flow of glucose precursors to the liver. [U-14C,3-3H]Glucose was used to investigate the effect of glucagon on the hepatic fructose-6-phosphate (F-6-P) cycle. Glucagon administration resulted in a rapid drop in the 3H/14C ratio of circulating glucose, suggesting an increase in F-6-P recycling caused by activation of FDPase with little or no decrease in phosphofructokinase. Such a change would direct substrate flux toward gluconeogenesis."}
{"id": "PMID:190047", "title": "Integrated control of hepatic glucose metabolism.", "content": "The rates of storage and release of carbohydrate by the liver are determined by the plasma concentrations of several blood-borne signals; most important are the concentrations of glucose, and of the hormones insulin and glucagon. To understand the complex control relationships of these three signals as they affect the liver, their individual dynamic influences have been determined experimentally, and the findings have been integrated by means of a computer simulation of the pathways of hepatic glycogen metabolism. The simulation studies have led to specific hypotheses about the biochemical effects of glucose and insulin on the liver. The simulation studies have also led to the conclusion that glucose exerts a rapid moment-to-moment influence on the rate of uptake of glucose by the liver. Insulin, however, by exerting a slower influence on the sensitivity of the liver to glucose, is very effective in \"optimizing\" the amount of glycogen which the liver stores during food intake. Thus, integrated experimental and simulation studies can lead to a view of a physiological regulating system which does not emerge from either approach used alone.-", "contents": "Integrated control of hepatic glucose metabolism. The rates of storage and release of carbohydrate by the liver are determined by the plasma concentrations of several blood-borne signals; most important are the concentrations of glucose, and of the hormones insulin and glucagon. To understand the complex control relationships of these three signals as they affect the liver, their individual dynamic influences have been determined experimentally, and the findings have been integrated by means of a computer simulation of the pathways of hepatic glycogen metabolism. The simulation studies have led to specific hypotheses about the biochemical effects of glucose and insulin on the liver. The simulation studies have also led to the conclusion that glucose exerts a rapid moment-to-moment influence on the rate of uptake of glucose by the liver. Insulin, however, by exerting a slower influence on the sensitivity of the liver to glucose, is very effective in \"optimizing\" the amount of glycogen which the liver stores during food intake. Thus, integrated experimental and simulation studies can lead to a view of a physiological regulating system which does not emerge from either approach used alone.-"}
{"id": "PMID:190048", "title": "Reversible inhibition of the motility of human spermatozoa by cytochalasin B.", "content": "Cytochalasin B inhibits the motility and metabolism of washed human spermatozoa at low concentrations (20 to 200 mum). Spermatozoal motility (primarily the frequency of flagellar contraction) declines slowly after addition of the antibiotic but is not abolished even after treatment for several hours. The addition of caffeine or dibutyrylcyclic adenosine 3' :5'-monophosphate to washed sperm suspensions increases the percentage of motile cells, the frequency of flagellar contraction, and the rate of glycolysis. These effects are blocked by cytochalasin B. However, cytochalasin B-treated spermatozoa regain their responsiveness to these agents when the antibiotic is washed out of supporting media. These effects are discussed in terms of an interaction of cytochalasin B with the sperm plasma membrane.", "contents": "Reversible inhibition of the motility of human spermatozoa by cytochalasin B. Cytochalasin B inhibits the motility and metabolism of washed human spermatozoa at low concentrations (20 to 200 mum). Spermatozoal motility (primarily the frequency of flagellar contraction) declines slowly after addition of the antibiotic but is not abolished even after treatment for several hours. The addition of caffeine or dibutyrylcyclic adenosine 3' :5'-monophosphate to washed sperm suspensions increases the percentage of motile cells, the frequency of flagellar contraction, and the rate of glycolysis. These effects are blocked by cytochalasin B. However, cytochalasin B-treated spermatozoa regain their responsiveness to these agents when the antibiotic is washed out of supporting media. These effects are discussed in terms of an interaction of cytochalasin B with the sperm plasma membrane."}
{"id": "PMID:190050", "title": "[Inhibition of spontaneous lymph vessel contraction evoked by transmural stimulation].", "content": "In isolated sections of mesenteric lymphatic vessels, the constrictory responses to transmural electrical stimulation were studied. Inhibition of the spontaneous rhythm occurring primarily at low frequencies was revealed as well as the inhibition following the excitatory effect of high--frequency stimulation. Analysis of the transmural inhibition showed the latter to occur as the result of activation of adrenergic nervous plexus and to be fulfilled by the beta--adrenoreceptors.", "contents": "[Inhibition of spontaneous lymph vessel contraction evoked by transmural stimulation]. In isolated sections of mesenteric lymphatic vessels, the constrictory responses to transmural electrical stimulation were studied. Inhibition of the spontaneous rhythm occurring primarily at low frequencies was revealed as well as the inhibition following the excitatory effect of high--frequency stimulation. Analysis of the transmural inhibition showed the latter to occur as the result of activation of adrenergic nervous plexus and to be fulfilled by the beta--adrenoreceptors."}
{"id": "PMID:190052", "title": "[The effects of ACTH, aminoglutehimide and hypophysectomy on the rat adrenal lipids (author's transl)].", "content": "The lipid patterns in the adrenal glands of rats with the adrenocortical steroidogenesis stimulated by ACTH or inhibited by hypophysectomy or by aminoglutehimide (AGT) were compared with those in intact rats. The administration of ACTH caused the gradual decrease in the concentration of cholesteryl ester with the preferential decrease in the proportion of arachidonic acid. The deposition of cholesteryl ester was observed in the adrenal glands of both hypophysectomized and AGT treated rats. Hypophysectomy was accompained by the increase in the proportion of 16:0 and 18:0 and the decrease of 18:2 and 20:3, while AGT administration caused the increase in the proportion of 20:4 and the decrease of 22:6 in the cholesteryl fraction, ACTH and AGT treatments or hypophysectomy resulted in minor alterations of the concentrations and fatty acid compositions of triglyceride and phospholipid. The marked differences in the concentration as well as fatty acid compositions of cholesteryl ester under the stimulated or inhibited adrenal steroidogenesis suggest the important role of fatty acids esterified with cholesterol in the steroid hormone synthesis.", "contents": "[The effects of ACTH, aminoglutehimide and hypophysectomy on the rat adrenal lipids (author's transl)]. The lipid patterns in the adrenal glands of rats with the adrenocortical steroidogenesis stimulated by ACTH or inhibited by hypophysectomy or by aminoglutehimide (AGT) were compared with those in intact rats. The administration of ACTH caused the gradual decrease in the concentration of cholesteryl ester with the preferential decrease in the proportion of arachidonic acid. The deposition of cholesteryl ester was observed in the adrenal glands of both hypophysectomized and AGT treated rats. Hypophysectomy was accompained by the increase in the proportion of 16:0 and 18:0 and the decrease of 18:2 and 20:3, while AGT administration caused the increase in the proportion of 20:4 and the decrease of 22:6 in the cholesteryl fraction, ACTH and AGT treatments or hypophysectomy resulted in minor alterations of the concentrations and fatty acid compositions of triglyceride and phospholipid. The marked differences in the concentration as well as fatty acid compositions of cholesteryl ester under the stimulated or inhibited adrenal steroidogenesis suggest the important role of fatty acids esterified with cholesterol in the steroid hormone synthesis."}
{"id": "PMID:190053", "title": "[Clinical study of pseudohypoparathyroidism Type I & Type II (author's transl)].", "content": "Pseudohypoparathyroidism (PHP) is a disorder characterized by renal and/or skeletal refractoriness to the effect of parathyroid hormone (PTH). In 1973, it was first proposed by Drezner et al that PHP could be divided into two types, e.g., PHP Type I and PHP Type II. PHP Type I is a disorder which fails to show the increase of urinary c-AMP and phosphaturia by the administration of PTH, but PHP Type II is that which responds to the administration of PTH with a marked rise of urinary c-AMP, but no increase of phosphate excretion, In 1974 Rodriguez et al demonstrated a patient with PHP Type II who restored normal renal responsiveness to PTH by calcium administration. Here we present two patients who fitted in the categories of PHP Type I & II, respectively, and restored normal renal responsiveness by the combined Ca-PTH administration or dibutyryl-cAMP infusion. Case I (PHP Type I) was a 31 yr old male with marked hypocalcemia and hyperphosphatemia, who showed neither increase of urinary c-AMP nor phosphate excretion in response to PTH infusion. Case II (PHP Type II), also diagnosed as Sj\u00f6gren syndrome was a 22 yr old female with relatively mild hypocalcemia and hyperphosphatemia, who showed a marked rise of ordinary c-AMP, but no increase of phosphate excretion by PTH administration. Acute infusion of calcium, followed by PTH administration restored renal responsiveness to PTH in both types, though calcium infusion showed only little effects. The patient of PHP Type I received calcium gluconate and Vitamin D therapy and serum Ca improved, when PTH or DBc-AMP was given with the reappearance of PTH-like action. Thus in PHP Type I, the lack of c-AMP response to PTH, coupled with the ability of infused DBc-AMP to evoke a normal renal response suggests that the metabolic defect in this disorder may exist in hormone receptor-adenyl cyclase complex. Calcium infusion followed by PTH administration probably might evoke calcium influx and c-AMP production, resulting in the reappearance of hormone action. In PHP Type II, as c-AMP generation system is intact, the metabolic defect can be thought to exist in the rather poorly defined process beyond c-AMP generation. The combined Ca-PTH administration also restored normal renal response, probably partly due to the improved calcium environment of renal tubular cells. Though it is difficult to explain why endogenously generated c-AMP had no effect, but DBc-AMP had on reappearance of PTH-like action, it is speculated that DBc-AMP may have much more stronger effects for intracellular receptor site of c-AMP in PHP Type II. Conclusively these results clearly suggest that the nature of the metabolic defects in PHP is not a genetically determined inrreversible disorder, but rather a functional one which can be reversibly restored by special conditioning.", "contents": "[Clinical study of pseudohypoparathyroidism Type I & Type II (author's transl)]. Pseudohypoparathyroidism (PHP) is a disorder characterized by renal and/or skeletal refractoriness to the effect of parathyroid hormone (PTH). In 1973, it was first proposed by Drezner et al that PHP could be divided into two types, e.g., PHP Type I and PHP Type II. PHP Type I is a disorder which fails to show the increase of urinary c-AMP and phosphaturia by the administration of PTH, but PHP Type II is that which responds to the administration of PTH with a marked rise of urinary c-AMP, but no increase of phosphate excretion, In 1974 Rodriguez et al demonstrated a patient with PHP Type II who restored normal renal responsiveness to PTH by calcium administration. Here we present two patients who fitted in the categories of PHP Type I & II, respectively, and restored normal renal responsiveness by the combined Ca-PTH administration or dibutyryl-cAMP infusion. Case I (PHP Type I) was a 31 yr old male with marked hypocalcemia and hyperphosphatemia, who showed neither increase of urinary c-AMP nor phosphate excretion in response to PTH infusion. Case II (PHP Type II), also diagnosed as Sj\u00f6gren syndrome was a 22 yr old female with relatively mild hypocalcemia and hyperphosphatemia, who showed a marked rise of ordinary c-AMP, but no increase of phosphate excretion by PTH administration. Acute infusion of calcium, followed by PTH administration restored renal responsiveness to PTH in both types, though calcium infusion showed only little effects. The patient of PHP Type I received calcium gluconate and Vitamin D therapy and serum Ca improved, when PTH or DBc-AMP was given with the reappearance of PTH-like action. Thus in PHP Type I, the lack of c-AMP response to PTH, coupled with the ability of infused DBc-AMP to evoke a normal renal response suggests that the metabolic defect in this disorder may exist in hormone receptor-adenyl cyclase complex. Calcium infusion followed by PTH administration probably might evoke calcium influx and c-AMP production, resulting in the reappearance of hormone action. In PHP Type II, as c-AMP generation system is intact, the metabolic defect can be thought to exist in the rather poorly defined process beyond c-AMP generation. The combined Ca-PTH administration also restored normal renal response, probably partly due to the improved calcium environment of renal tubular cells. Though it is difficult to explain why endogenously generated c-AMP had no effect, but DBc-AMP had on reappearance of PTH-like action, it is speculated that DBc-AMP may have much more stronger effects for intracellular receptor site of c-AMP in PHP Type II. Conclusively these results clearly suggest that the nature of the metabolic defects in PHP is not a genetically determined inrreversible disorder, but rather a functional one which can be reversibly restored by special conditioning."}
{"id": "PMID:190054", "title": "[ACTH secretion and adrenocortical responsiveness in Cushing's syndrome due to adrenocortical hyperplasia (author's transl)].", "content": "A radioimmunoassay for plasma ACTH has been developed utilizing highly purified human ACTH (Li) labelled with 125I by the lactoperoxidase method as a tracer and an ACTH antibody produced by immunization of rabbits with ACTH-Z (Organon). The assay is highly specific, reproducible and sensitive to 20 pg of ACTH per ml. Utilizing this technique, endogenous ACTH secretion, adrenal responsiveness to endogenous ACTH and hypothalamic pituitary adrenal feedback mechanisms have been assessed in normal subjects and in patients with Cushing's syndrome due to adrenocortical hyperplasia and nodular cortical hyperplasia. The potential effect of a negative feedback mechanism on the circadian rhythmicity after SU-4885 administration was assessed by initiating SU-4885 either at 9 p.m. or 8 a.m. In normal subjects, the circadian rhythm of ACTH was persistent and independent of a decrease in cortisol. However, in a single case of Cushing's syndrome due to adrenocortical hyperplasia, the circadian rhythm was different from that of normal subjects, possibly influenced by a negative feedback mechanism when SU-4885 was initiated at 8 a.m. In Cushing's syndrome due to adrenocortical and nodular cortical hyperplasia, a significant correlation was observed between the mean plasma ACTH and urinary 17-OHCS values before and after SU-4885 administration (r=0.743, p less than0.01). A significant correlation was also obtained in normal subjects between plasma ACTH and urinary 17-OHCS values (r=0.889, p less than 0.01). However, there was quantitatively more 17-OHCS excreted in the urine for a given plasma ACTH level in patients with Cushing's syndrome than in normal subjects. To assess the relative biological activity of endogenous and exogenously administered ACTH, the ratio of daily 17-OHCS during SU-4885 administration and Cortrosyn-Z administration was expressed as the Cortrosyn Equivalent Quotient (C.E.Q.). The correlation between plasma ACTH and C.E.Q. was similar and significant for normal subjects and patients with Cushing's syndrome (r=0.670, p less than 0.01). These data suggest that there is hyper-responsiveness of the adrenal glands to endogenous ACTH in Cushing's syndrome due to adrenocortical hyperplasia and nodular cortical hyperplasia and that the adrenal hyperactivity is not engendered by a qualitative change in the ACTH release from the pituitary gland. To assess pituitary suppressibility, dexamethasone was administered 40 days or more later following total adrenalectomy in 9 patients with Cushing's syndrome, 6 with adrenocortical hyperplasia and 3 with nodular cortical hyperplasia. One day after discontinuation of substitution therapy, 2 mg of dexamethasone was administered orally followed on successive days by 4 and 8 mg doses. In each instance, dexamethasone was given at midnight and the plasma ACTH concentration was determined at 9:00 a.m. on the day before and after administration of the dexamethasone. A patient with Addison's disease was studied as a control...", "contents": "[ACTH secretion and adrenocortical responsiveness in Cushing's syndrome due to adrenocortical hyperplasia (author's transl)]. A radioimmunoassay for plasma ACTH has been developed utilizing highly purified human ACTH (Li) labelled with 125I by the lactoperoxidase method as a tracer and an ACTH antibody produced by immunization of rabbits with ACTH-Z (Organon). The assay is highly specific, reproducible and sensitive to 20 pg of ACTH per ml. Utilizing this technique, endogenous ACTH secretion, adrenal responsiveness to endogenous ACTH and hypothalamic pituitary adrenal feedback mechanisms have been assessed in normal subjects and in patients with Cushing's syndrome due to adrenocortical hyperplasia and nodular cortical hyperplasia. The potential effect of a negative feedback mechanism on the circadian rhythmicity after SU-4885 administration was assessed by initiating SU-4885 either at 9 p.m. or 8 a.m. In normal subjects, the circadian rhythm of ACTH was persistent and independent of a decrease in cortisol. However, in a single case of Cushing's syndrome due to adrenocortical hyperplasia, the circadian rhythm was different from that of normal subjects, possibly influenced by a negative feedback mechanism when SU-4885 was initiated at 8 a.m. In Cushing's syndrome due to adrenocortical and nodular cortical hyperplasia, a significant correlation was observed between the mean plasma ACTH and urinary 17-OHCS values before and after SU-4885 administration (r=0.743, p less than0.01). A significant correlation was also obtained in normal subjects between plasma ACTH and urinary 17-OHCS values (r=0.889, p less than 0.01). However, there was quantitatively more 17-OHCS excreted in the urine for a given plasma ACTH level in patients with Cushing's syndrome than in normal subjects. To assess the relative biological activity of endogenous and exogenously administered ACTH, the ratio of daily 17-OHCS during SU-4885 administration and Cortrosyn-Z administration was expressed as the Cortrosyn Equivalent Quotient (C.E.Q.). The correlation between plasma ACTH and C.E.Q. was similar and significant for normal subjects and patients with Cushing's syndrome (r=0.670, p less than 0.01). These data suggest that there is hyper-responsiveness of the adrenal glands to endogenous ACTH in Cushing's syndrome due to adrenocortical hyperplasia and nodular cortical hyperplasia and that the adrenal hyperactivity is not engendered by a qualitative change in the ACTH release from the pituitary gland. To assess pituitary suppressibility, dexamethasone was administered 40 days or more later following total adrenalectomy in 9 patients with Cushing's syndrome, 6 with adrenocortical hyperplasia and 3 with nodular cortical hyperplasia. One day after discontinuation of substitution therapy, 2 mg of dexamethasone was administered orally followed on successive days by 4 and 8 mg doses. In each instance, dexamethasone was given at midnight and the plasma ACTH concentration was determined at 9:00 a.m. on the day before and after administration of the dexamethasone. A patient with Addison's disease was studied as a control..."}
{"id": "PMID:190055", "title": "Progressive systemic sclerosis (scleroderma). First case report in a Nigerian.", "content": "The first case of progressive systemic sclerosis in a Nigerian is described. In addition to the typical features of the disease, the case shows affection of the peripheral nerves, a very rare complication. The latter led to a mistaken diagnosis of leprosy. The reasons for the rarity of this disorder in the indigenous Africans and its differentiating features from leprosy are discussed.", "contents": "Progressive systemic sclerosis (scleroderma). First case report in a Nigerian. The first case of progressive systemic sclerosis in a Nigerian is described. In addition to the typical features of the disease, the case shows affection of the peripheral nerves, a very rare complication. The latter led to a mistaken diagnosis of leprosy. The reasons for the rarity of this disorder in the indigenous Africans and its differentiating features from leprosy are discussed."}
{"id": "PMID:190057", "title": "Secretion of immunoreactive insulin and glucagon in hamsters bearing a transplantable insuloma.", "content": "Glucose, insulin (IRI), pancreatic (IRG) and total (GLI) immunoreactive glucagon were measured in the serum of normal hamsters and of hamsters with an insulin- and glucagon-secreting, transplantable insuloma. The tumor-bearing animals were hypoglycemic, hyperinsulinemic and hyperglucagonemic. The pancreatic islets of tumor-bearing animals secreted less glucagon and insulin in response to arginine or to changes in the glucose concentration of the medium, than did the islets of control hamsters. In addition, the introduction of glucose into the gastro-intestinal tract, which caused a significant rise in the serum GLI concentration of normal hamsters, failed to do so in the tumor-bearing animals. The results suggest that  the high levels of serum glucagon and insulin induced by the tumor, suppressed IRI, IRG and GLI secretion in these animals.", "contents": "Secretion of immunoreactive insulin and glucagon in hamsters bearing a transplantable insuloma. Glucose, insulin (IRI), pancreatic (IRG) and total (GLI) immunoreactive glucagon were measured in the serum of normal hamsters and of hamsters with an insulin- and glucagon-secreting, transplantable insuloma. The tumor-bearing animals were hypoglycemic, hyperinsulinemic and hyperglucagonemic. The pancreatic islets of tumor-bearing animals secreted less glucagon and insulin in response to arginine or to changes in the glucose concentration of the medium, than did the islets of control hamsters. In addition, the introduction of glucose into the gastro-intestinal tract, which caused a significant rise in the serum GLI concentration of normal hamsters, failed to do so in the tumor-bearing animals. The results suggest that  the high levels of serum glucagon and insulin induced by the tumor, suppressed IRI, IRG and GLI secretion in these animals."}
{"id": "PMID:190058", "title": "Somatostatin: a review of its effects especially in human beings.", "content": "A review is given of the early 1976 situation in somatostatin research: the effects on pituitary hormones and the effects outside the pituitary gland, the production of somatostatin outside the hypothalamus, the artificial analogues, the problem of \"side effects\", and the mode of action. The possible clinical applications of somatostatin and somatostatin analogues are discussed.", "contents": "Somatostatin: a review of its effects especially in human beings. A review is given of the early 1976 situation in somatostatin research: the effects on pituitary hormones and the effects outside the pituitary gland, the production of somatostatin outside the hypothalamus, the artificial analogues, the problem of \"side effects\", and the mode of action. The possible clinical applications of somatostatin and somatostatin analogues are discussed."}
{"id": "PMID:190063", "title": "Endocrine and cardiovascular consequences of angiotensin converting enzyme inhibition.", "content": "One of several novel peptidic inhibitors of angiotensin converting enzyme (CEI) has been studied intravenously both in normal male volunteers and severely hypertensive patients without any clinically significant adversity or intolerance. Hypertensive patients experienced a significant yet gradual reduction in resting arterial pressure without hypotension. The addition of a diuretic agent was observed to potentiate this antihypertensive effect. Normal, sodium replete volunteers received this nonapeptide intravenously in doses up to 2-0 mg/kg without any significant cardiovascular effect. Both patients and normal subjects exhibited reversible dose related increases in angiotensin I and renin levels after receiving the peptide. The plasma renin response to tilting was also potentiated by CEI. These findings suggest that intravenous CEI may be of value in the treatment of severely elevated hypertension and as a tool to evaluate vasoconstrictor and volume factors in hypertension.", "contents": "Endocrine and cardiovascular consequences of angiotensin converting enzyme inhibition. One of several novel peptidic inhibitors of angiotensin converting enzyme (CEI) has been studied intravenously both in normal male volunteers and severely hypertensive patients without any clinically significant adversity or intolerance. Hypertensive patients experienced a significant yet gradual reduction in resting arterial pressure without hypotension. The addition of a diuretic agent was observed to potentiate this antihypertensive effect. Normal, sodium replete volunteers received this nonapeptide intravenously in doses up to 2-0 mg/kg without any significant cardiovascular effect. Both patients and normal subjects exhibited reversible dose related increases in angiotensin I and renin levels after receiving the peptide. The plasma renin response to tilting was also potentiated by CEI. These findings suggest that intravenous CEI may be of value in the treatment of severely elevated hypertension and as a tool to evaluate vasoconstrictor and volume factors in hypertension."}
{"id": "PMID:190064", "title": "Properties of detergent-solubilized adenylate cyclase and gonadotropin receptors of testis and ovary.", "content": "The relationship between solubilized hormone-binding sites and adenylate cyclase was examined in detergent extracts of particulate testis and ovarian fractions. Both basal and fluoride-stimulated activities of the particulate enzyme were markedly increased in the presence of detergents, and about 60% of the enzyme activity was recovered as the soluble form in the 300,000 g supernatant. Enhancement of adenylate cyclase activity was more marked with Lubrol PX and WX than with Triton X-100, and the highest recovery and activation of adenylate cyclase were obtained with 0.5% Lubrol PX. The particulate and solubilized testicular enzymes were more active in the presence of Mn2+, and the detergent-extracted soluble ovarian cyclase showed a small and inconstant response to gonadotropin. Fractionation of Lubrol-solubilized testis and ovarian preparations on Sepharose 6B showed two peaks of free gonadotropin receptors. The binding activity eluted with Kav of 0.32 corresponded to the receptor sites previously characterized in detergent-solubilized gonadal particles, and was coincident with the elution profile of adenylate cyclase activity. An additional peak of binding activity with Kav of 0.56 was not accompanied by detectable adenylate cyclase activity. These observations suggest that the peak of larger molecular size could represent dissociated receptors or binding sites which were not coupled to adenylate cyclase.", "contents": "Properties of detergent-solubilized adenylate cyclase and gonadotropin receptors of testis and ovary. The relationship between solubilized hormone-binding sites and adenylate cyclase was examined in detergent extracts of particulate testis and ovarian fractions. Both basal and fluoride-stimulated activities of the particulate enzyme were markedly increased in the presence of detergents, and about 60% of the enzyme activity was recovered as the soluble form in the 300,000 g supernatant. Enhancement of adenylate cyclase activity was more marked with Lubrol PX and WX than with Triton X-100, and the highest recovery and activation of adenylate cyclase were obtained with 0.5% Lubrol PX. The particulate and solubilized testicular enzymes were more active in the presence of Mn2+, and the detergent-extracted soluble ovarian cyclase showed a small and inconstant response to gonadotropin. Fractionation of Lubrol-solubilized testis and ovarian preparations on Sepharose 6B showed two peaks of free gonadotropin receptors. The binding activity eluted with Kav of 0.32 corresponded to the receptor sites previously characterized in detergent-solubilized gonadal particles, and was coincident with the elution profile of adenylate cyclase activity. An additional peak of binding activity with Kav of 0.56 was not accompanied by detectable adenylate cyclase activity. These observations suggest that the peak of larger molecular size could represent dissociated receptors or binding sites which were not coupled to adenylate cyclase."}
{"id": "PMID:190065", "title": "The use of dynamic models to study the role of calcium in the oxytocin-induced contractions of the uterus.", "content": "The question as to whether calcium can be considered to be a mediator of oxytocin-induced myometrial contraction has been investigated. Assuming that the contraction is linearly proportional to the myoplasmic calcium concentration, several possible molecular mechanisms leading to its increase (calcium release from the cell membrane, acceleration of calcium transport from extracellular space by a 'gate' mechanism, release from intracellular organelles, blockade of calcium pumps) were modelled on an analog computer. The oxytocin intervention in the calcium distribution was mimicked by a discontinuous change of the appropriate rate constants. The computed transient simulating the myoplasmic calcium concentration was then compared with an experimental time profile of uterine tension. The result of screening the models shows that oxytocin must act predominantly via release of calcium bound to the cell membrane. A quantitative comparison, however, requires that the kinetics of oxytocin distribution in myometrium also be considered in the model. The problem treated in this paper demonstrates the possibilities and limitations of a screening procedure based upon direct comparison of time profiles of experimental processes with several computed model alternatives.", "contents": "The use of dynamic models to study the role of calcium in the oxytocin-induced contractions of the uterus. The question as to whether calcium can be considered to be a mediator of oxytocin-induced myometrial contraction has been investigated. Assuming that the contraction is linearly proportional to the myoplasmic calcium concentration, several possible molecular mechanisms leading to its increase (calcium release from the cell membrane, acceleration of calcium transport from extracellular space by a 'gate' mechanism, release from intracellular organelles, blockade of calcium pumps) were modelled on an analog computer. The oxytocin intervention in the calcium distribution was mimicked by a discontinuous change of the appropriate rate constants. The computed transient simulating the myoplasmic calcium concentration was then compared with an experimental time profile of uterine tension. The result of screening the models shows that oxytocin must act predominantly via release of calcium bound to the cell membrane. A quantitative comparison, however, requires that the kinetics of oxytocin distribution in myometrium also be considered in the model. The problem treated in this paper demonstrates the possibilities and limitations of a screening procedure based upon direct comparison of time profiles of experimental processes with several computed model alternatives."}
{"id": "PMID:190066", "title": "Prolactin binding in rat testis: specific receptors in interstitial cells.", "content": "Specific receptors for [125I]hPrl (human prolactin) are present in membrane preparations of rat testis. The receptors are specific for lactogenic hormones (prolactin and human growth hormone) but do not bind gonadotropins. The prolactin receptors are localized exclusively in the interstitial cell tissue, and are not present in membrane preparations from isolated seminiferous tubules. The localization of prolactin receptors interstitial tissue suggests that the effect of prolactin on LH/hCG-stimulated testosterone production is due to a direct effect of prolactin of Leydig cells.", "contents": "Prolactin binding in rat testis: specific receptors in interstitial cells. Specific receptors for [125I]hPrl (human prolactin) are present in membrane preparations of rat testis. The receptors are specific for lactogenic hormones (prolactin and human growth hormone) but do not bind gonadotropins. The prolactin receptors are localized exclusively in the interstitial cell tissue, and are not present in membrane preparations from isolated seminiferous tubules. The localization of prolactin receptors interstitial tissue suggests that the effect of prolactin on LH/hCG-stimulated testosterone production is due to a direct effect of prolactin of Leydig cells."}
{"id": "PMID:190067", "title": "Involvement of intracellular calcium in hormone secretion from pituitary cells.", "content": "Cells were dissociated from normal rat pituitaries by a combination of mechanical agitation and enzymatic action, seeded into culture flasks and grown in monolayer culture. When such cells were exposed to an extract of the hypothalamic stalk-median eminence area (HSME) a dose-dependent secretion of ACTH was observed. A 2-h exposure to Ca-free media significantly reduced the HSME-stimulated release of ACTH but the measured levels were still greater than the unstimulated controls. When the 45Ca2+ uptake into the cultured cells was measured both control and HSME-stimulated cells yielded identical results (60-80 nmol Ca/mg cell protein). Upon removal of the calcium associated with the surface coat it was found that HSME actually decreased the cellular uptake of calcium. Since variations in uptake  can result from changes in influx or efflux as well as from variations in pool size or turnover times of calcium exchange with intracellular compartments, a series of isotope washout experiments were performed. Neither HSME nor theophyline affected the rate constant of calcium efflux from what is believed to be the cytosol pool to the extracellular media. Both agents, however, prompted a shift of intracellular calcium into a more tightly bound compartment. The data suggest that the calcium required for pituitary hormone secretion is derived primarily from an intracellular rather than extracellular origin. It may be that, via the action of cyclic AMP, such calcium can be mobilized from intracellular stores and shifted to a more tightly bound compartment where it can participate in the intracellular processes associated with secretion.", "contents": "Involvement of intracellular calcium in hormone secretion from pituitary cells. Cells were dissociated from normal rat pituitaries by a combination of mechanical agitation and enzymatic action, seeded into culture flasks and grown in monolayer culture. When such cells were exposed to an extract of the hypothalamic stalk-median eminence area (HSME) a dose-dependent secretion of ACTH was observed. A 2-h exposure to Ca-free media significantly reduced the HSME-stimulated release of ACTH but the measured levels were still greater than the unstimulated controls. When the 45Ca2+ uptake into the cultured cells was measured both control and HSME-stimulated cells yielded identical results (60-80 nmol Ca/mg cell protein). Upon removal of the calcium associated with the surface coat it was found that HSME actually decreased the cellular uptake of calcium. Since variations in uptake  can result from changes in influx or efflux as well as from variations in pool size or turnover times of calcium exchange with intracellular compartments, a series of isotope washout experiments were performed. Neither HSME nor theophyline affected the rate constant of calcium efflux from what is believed to be the cytosol pool to the extracellular media. Both agents, however, prompted a shift of intracellular calcium into a more tightly bound compartment. The data suggest that the calcium required for pituitary hormone secretion is derived primarily from an intracellular rather than extracellular origin. It may be that, via the action of cyclic AMP, such calcium can be mobilized from intracellular stores and shifted to a more tightly bound compartment where it can participate in the intracellular processes associated with secretion."}
{"id": "PMID:190069", "title": "Innocuity and toxicity testing of non-viral components of foot-and-mouth disease vaccines.", "content": "Some biological properties of 3 different adjuvants: saponin, DEAE-dextran and sodium azide applied in foot-and-mouth vaccines have been studied. As tested in guinea pigs, by dialysis of various batches of saponin, the author succeeded in reducing their toxicity by 80 to 90%, their hemolytic activity by 60 to 75% and their inflammatory capacity by 40 to 50%, whereas in cattle the inflammatory capacity of dialyzed saponin batches decreased by 80 to 90%. The inflammatory capacity of DEAE-dextran is about 50 to 60% less than that of the saponin. The effect of saponin and sodium azide has directly been studied in virus suspension also. Neither the saponin nor the sodium azide affected adversely the infectivity and immunogenicity of the antigen. The loss of potency due to the storage of the vaccine is not in relationship with the presence of the two above-named components.", "contents": "Innocuity and toxicity testing of non-viral components of foot-and-mouth disease vaccines. Some biological properties of 3 different adjuvants: saponin, DEAE-dextran and sodium azide applied in foot-and-mouth vaccines have been studied. As tested in guinea pigs, by dialysis of various batches of saponin, the author succeeded in reducing their toxicity by 80 to 90%, their hemolytic activity by 60 to 75% and their inflammatory capacity by 40 to 50%, whereas in cattle the inflammatory capacity of dialyzed saponin batches decreased by 80 to 90%. The inflammatory capacity of DEAE-dextran is about 50 to 60% less than that of the saponin. The effect of saponin and sodium azide has directly been studied in virus suspension also. Neither the saponin nor the sodium azide affected adversely the infectivity and immunogenicity of the antigen. The loss of potency due to the storage of the vaccine is not in relationship with the presence of the two above-named components."}
{"id": "PMID:190070", "title": "Study on toxicity of Bordetella pertussis cultures and antigens.", "content": "The toxicity of 201 Bordetella pertussis strains isolated in Belgrade has been studied. The strains were grown on a modification of Cohen and Wheeler's medium. LD50 of examined strains ranging between 1.06 and 1.95 billion bacteria in 35 (17.41%), between 2.04 and 4.83 billion bacteria in 92 (45.77%) and between 5.31 and 7.79 billion bacteria in 46 (22.88%) were found. Low toxic cultures of B. pertussis strains with LD50 ranging between 9.0 and 14.1 billion bacteria in 28 (13.43%) were obtained. The culture of the strains with low toxicity was 7 to 14 times more toxic than those prepared from the strains with low toxicity. In the cultures of 51 B. pertussis strains, toxicity for mice was not correlated with the number of viable cells. The toxic substances which influenced the loss of mouse weight were found in the culture filtrate of B. pertussis. A considerable detoxifying effect of heating at 56 degrees C for 30 min on liquid cultures prepared from highly toxic strains of B. pertussis was observed. The susceptibility of two different strains of mice for pertussis vaccine has been examined. The Albany strain of mice was less susceptible to toxicity control of the vaccine by mouse-weight-gain test than the Torlak strain.", "contents": "Study on toxicity of Bordetella pertussis cultures and antigens. The toxicity of 201 Bordetella pertussis strains isolated in Belgrade has been studied. The strains were grown on a modification of Cohen and Wheeler's medium. LD50 of examined strains ranging between 1.06 and 1.95 billion bacteria in 35 (17.41%), between 2.04 and 4.83 billion bacteria in 92 (45.77%) and between 5.31 and 7.79 billion bacteria in 46 (22.88%) were found. Low toxic cultures of B. pertussis strains with LD50 ranging between 9.0 and 14.1 billion bacteria in 28 (13.43%) were obtained. The culture of the strains with low toxicity was 7 to 14 times more toxic than those prepared from the strains with low toxicity. In the cultures of 51 B. pertussis strains, toxicity for mice was not correlated with the number of viable cells. The toxic substances which influenced the loss of mouse weight were found in the culture filtrate of B. pertussis. A considerable detoxifying effect of heating at 56 degrees C for 30 min on liquid cultures prepared from highly toxic strains of B. pertussis was observed. The susceptibility of two different strains of mice for pertussis vaccine has been examined. The Albany strain of mice was less susceptible to toxicity control of the vaccine by mouse-weight-gain test than the Torlak strain."}
{"id": "PMID:190071", "title": "An islet cell carcinoma containing glucagon and insulin. Chronic glucagon excess and glucose homeostasis.", "content": "Described here is a patient who had an islet cell carcinoma containing both glucagon (glucagonoma) and insulin (insulinoma). Complete removal of the tumor was possible. Immunoreactive glucagon (IRG) could be extracted from all parts of the tumor (approximately 50 mug./gm.) and was shown to be fully bioactive. Immunoreactive insulin (IRI) could be extracted only from one section of the tumor (approximately 30 mug./gm.). The clinical and biochemical manifestations of the disease were dermatitis, diabetes, weight loss, anemia, hypoaminoacidemia, and hyperketonemia. The diabetes was characterized by low or normal fasting blood glucose concentrations and by impaired glucose tolerance (Kg = 0.4). After complete removal of the tumor, the dermatitis cleared, the catabolic state changed into an anabolic state, blood amino acid concentrations increased, and blood ketone-body concentrations decreased. Fasting blood glucose concentrations, however, rose above 200 mg./dl., and glucose tolerance declined further (Kg = 0.15). Hourly blood sampling for 24 hours, intravenous and oral glucose tolerance tests, intravenous arginine and tolbutamide tolerance tests with serial determinations of IRG, IRI, and blood glucose were performed preoperatively and again two weeks and two months postoperatively. The results of these studies demonstrated marked abnormalities in the stimulation and suppression of glucagon and insulin release. In addition, they failed to demonstrate a glycemic effect on the chronically elevated glucagon concentrations in this patient, while identifying insulin as the dominant factor determining blood glucose homeostasis.", "contents": "An islet cell carcinoma containing glucagon and insulin. Chronic glucagon excess and glucose homeostasis. Described here is a patient who had an islet cell carcinoma containing both glucagon (glucagonoma) and insulin (insulinoma). Complete removal of the tumor was possible. Immunoreactive glucagon (IRG) could be extracted from all parts of the tumor (approximately 50 mug./gm.) and was shown to be fully bioactive. Immunoreactive insulin (IRI) could be extracted only from one section of the tumor (approximately 30 mug./gm.). The clinical and biochemical manifestations of the disease were dermatitis, diabetes, weight loss, anemia, hypoaminoacidemia, and hyperketonemia. The diabetes was characterized by low or normal fasting blood glucose concentrations and by impaired glucose tolerance (Kg = 0.4). After complete removal of the tumor, the dermatitis cleared, the catabolic state changed into an anabolic state, blood amino acid concentrations increased, and blood ketone-body concentrations decreased. Fasting blood glucose concentrations, however, rose above 200 mg./dl., and glucose tolerance declined further (Kg = 0.15). Hourly blood sampling for 24 hours, intravenous and oral glucose tolerance tests, intravenous arginine and tolbutamide tolerance tests with serial determinations of IRG, IRI, and blood glucose were performed preoperatively and again two weeks and two months postoperatively. The results of these studies demonstrated marked abnormalities in the stimulation and suppression of glucagon and insulin release. In addition, they failed to demonstrate a glycemic effect on the chronically elevated glucagon concentrations in this patient, while identifying insulin as the dominant factor determining blood glucose homeostasis."}
{"id": "PMID:190072", "title": "The cyclic AMP response to glucagon. Comparison of tissue and plasma cyclic AMP levels in the rabbit.", "content": "The effects of glucagon on tissue and plasma cyclic AMP levels have been investigated in rabbits anesthetized with urethane. Glucagon (2 nmole/kg.) caused at least a twofold increase in hepatic cyclic AMP, which reached a peak within two minutes and declined to basal values after 40 minutes. Plasma cyclic AMP also increased at least twofold, reaching a peak at 10 minutes and declining to basal values after 60 minutes. Glucagon (20 nmole/kg.) stimulated hepatic and plasma cyclic AMP in a manner indistinguishable from that observed at the lower dose. Hepatectomy abolished the plasma cyclic AMP responses to glucagon, and no significant stimulation of cyclic AMP concentration was noted in the heart, adipose tissue, small bowel, or kidney. Cyclic AMP hydrolysis was estimated in blood taken before and after administration of glucagon. Glucagon (2 nmole/kg.) increased cyclic AMP hydrolysis slightly, but this was explained by the raised cyclic AMP levels. By contrast, cyclic AMP hydrolysis increased two-to-threefold in blood taken 20 and 40 minutes after glucagon (20 nmole/kg.). The higher dose of glucagon also stimulated cyclic AMP hydrolysis in crude liver homogenate, which could not be explained by increases in cyclic AMP concentration. The increase in cyclic AMP hydrolysis observed in blood and liver may partly explain the failure to show additional stimulation of hepatic and plasma cyclic AMP levels with the higher dose of glucagon. Despite the changes in cyclic AMP hydrolysis, a highly significant correlation was observed in individual rabbits between the hepatic and plasma cyclic AMP responses to glucagon (2 and 20 nmole/kg.), when these were calculated as incremental areas above mean basal levels. It is suggested that measurement of plasma cyclic AMP levels after stimulation by glucagon may be an accurate index of the hepatic cyclic AMP response to glucagon in vivo.", "contents": "The cyclic AMP response to glucagon. Comparison of tissue and plasma cyclic AMP levels in the rabbit. The effects of glucagon on tissue and plasma cyclic AMP levels have been investigated in rabbits anesthetized with urethane. Glucagon (2 nmole/kg.) caused at least a twofold increase in hepatic cyclic AMP, which reached a peak within two minutes and declined to basal values after 40 minutes. Plasma cyclic AMP also increased at least twofold, reaching a peak at 10 minutes and declining to basal values after 60 minutes. Glucagon (20 nmole/kg.) stimulated hepatic and plasma cyclic AMP in a manner indistinguishable from that observed at the lower dose. Hepatectomy abolished the plasma cyclic AMP responses to glucagon, and no significant stimulation of cyclic AMP concentration was noted in the heart, adipose tissue, small bowel, or kidney. Cyclic AMP hydrolysis was estimated in blood taken before and after administration of glucagon. Glucagon (2 nmole/kg.) increased cyclic AMP hydrolysis slightly, but this was explained by the raised cyclic AMP levels. By contrast, cyclic AMP hydrolysis increased two-to-threefold in blood taken 20 and 40 minutes after glucagon (20 nmole/kg.). The higher dose of glucagon also stimulated cyclic AMP hydrolysis in crude liver homogenate, which could not be explained by increases in cyclic AMP concentration. The increase in cyclic AMP hydrolysis observed in blood and liver may partly explain the failure to show additional stimulation of hepatic and plasma cyclic AMP levels with the higher dose of glucagon. Despite the changes in cyclic AMP hydrolysis, a highly significant correlation was observed in individual rabbits between the hepatic and plasma cyclic AMP responses to glucagon (2 and 20 nmole/kg.), when these were calculated as incremental areas above mean basal levels. It is suggested that measurement of plasma cyclic AMP levels after stimulation by glucagon may be an accurate index of the hepatic cyclic AMP response to glucagon in vivo."}
{"id": "PMID:190073", "title": "Hypoglycemia in man pathologic and physiologic variants.", "content": "To determine if an effective method existed for distinguishing the physiologic hypoglycemia of fasting from pathologic hypoglycemia, 72-hour fasts were conducted in 60 women and 20 men of normal weight, in 16 obese subjects, and in six of 11 patient with insulinomas. Only the pattern of change of the immunoreactive-insulin-to-glucose ratio (the I/G ratio), calculated at major time intervals of the fast, provided a clear-cut distinction between these groups; plasma glucose values alone could not make this distinction. The mean fasting I/G ratio was calculated for each subject from that subject's I/G ratios at 12-hour intervals during the fasting period. In no single case did the mean I/G ratio during fasting for an individual of normal weight equal or exceed the control I/G. I/G ratios increased dramatically during fasting in each patient with an insulinomas. Normal obese patients (15% greater than ideal body weight) did not provide a diagnostic problem, since, regardless of sex, glucose values of less than 55 mg/dl. did not occur. Although the pattern of change of the I/G ratio was extremely useful, the basal I/G ratio alone was potentially misleading; this was due to overlap of basal I/G ratios between subjects with simple obesity and patients with insulinomas. In addition, absolute values for the I/G ratio varied with the technique employed for measuring glucose and insulin. Change of the I/G ratio, however, was independent of the techniques used for measuring glucose and insulin. DIABETES 26:161-65, March, 1977.", "contents": "Hypoglycemia in man pathologic and physiologic variants. To determine if an effective method existed for distinguishing the physiologic hypoglycemia of fasting from pathologic hypoglycemia, 72-hour fasts were conducted in 60 women and 20 men of normal weight, in 16 obese subjects, and in six of 11 patient with insulinomas. Only the pattern of change of the immunoreactive-insulin-to-glucose ratio (the I/G ratio), calculated at major time intervals of the fast, provided a clear-cut distinction between these groups; plasma glucose values alone could not make this distinction. The mean fasting I/G ratio was calculated for each subject from that subject's I/G ratios at 12-hour intervals during the fasting period. In no single case did the mean I/G ratio during fasting for an individual of normal weight equal or exceed the control I/G. I/G ratios increased dramatically during fasting in each patient with an insulinomas. Normal obese patients (15% greater than ideal body weight) did not provide a diagnostic problem, since, regardless of sex, glucose values of less than 55 mg/dl. did not occur. Although the pattern of change of the I/G ratio was extremely useful, the basal I/G ratio alone was potentially misleading; this was due to overlap of basal I/G ratios between subjects with simple obesity and patients with insulinomas. In addition, absolute values for the I/G ratio varied with the technique employed for measuring glucose and insulin. Change of the I/G ratio, however, was independent of the techniques used for measuring glucose and insulin. DIABETES 26:161-65, March, 1977."}
{"id": "PMID:190074", "title": "Transient stimulatory effect of sustained hyperglucagonemia on splanchnic glucose production in normal and diabetic man.", "content": "Insulin can modulate glucagon-stimulated hepatic glucose production and is considered to be the major factor acting in vivo to exert a couterregulatory action to glucagon. The insulin-dependent diabetic, therefore, might be especially vulnerable to enhanced hepatic glucose production promoted by glucagon. To investigate this hypothesis, low-dose glucagon infusions were administered to normal and diabetic men to compare the effects of glucagon on net splanchnic glucose production (NSGP). Four normal and three insulin-dependent, ketosis-prone, hyperglycemic diabetic men (insulin withheld for 24 hours) underwent brachial-artery-hepatic-vein catheterization. Each received a 90-minute glucagon infusion at 5 ng/kg./min. Glucagon levels rose four-to-fivefold in both groups, plateauing at 300-600 pg./ml. In the normals, NSGP rose from 92+/-12 to 211+/-31 mg./min. at 15 minutes and returned to basal levels by 45 minutes. Insulin measured in the hepatic vein rose from 19+/-6 to 33+/-11 muU/.ml., while plasma glucose rose 17 mg./dl. In the insulin-dependent diabetics, NSGP rose from 78+/-24 to a peak of 221+/-33 mg./min. at 30 minutes and then fell sharply to 113+/-15 mg./min. at 60 minutes despite continuing hyperglucagonemia. Plasma glucose in the diabetics rose 21 mg./dl. These data suggest a mechanism that acts to rapidly diminish glucagon-induced hepatic glucose production in diabetic man but does not appear to be mediated by increased insulin secretion.", "contents": "Transient stimulatory effect of sustained hyperglucagonemia on splanchnic glucose production in normal and diabetic man. Insulin can modulate glucagon-stimulated hepatic glucose production and is considered to be the major factor acting in vivo to exert a couterregulatory action to glucagon. The insulin-dependent diabetic, therefore, might be especially vulnerable to enhanced hepatic glucose production promoted by glucagon. To investigate this hypothesis, low-dose glucagon infusions were administered to normal and diabetic men to compare the effects of glucagon on net splanchnic glucose production (NSGP). Four normal and three insulin-dependent, ketosis-prone, hyperglycemic diabetic men (insulin withheld for 24 hours) underwent brachial-artery-hepatic-vein catheterization. Each received a 90-minute glucagon infusion at 5 ng/kg./min. Glucagon levels rose four-to-fivefold in both groups, plateauing at 300-600 pg./ml. In the normals, NSGP rose from 92+/-12 to 211+/-31 mg./min. at 15 minutes and returned to basal levels by 45 minutes. Insulin measured in the hepatic vein rose from 19+/-6 to 33+/-11 muU/.ml., while plasma glucose rose 17 mg./dl. In the insulin-dependent diabetics, NSGP rose from 78+/-24 to a peak of 221+/-33 mg./min. at 30 minutes and then fell sharply to 113+/-15 mg./min. at 60 minutes despite continuing hyperglucagonemia. Plasma glucose in the diabetics rose 21 mg./dl. These data suggest a mechanism that acts to rapidly diminish glucagon-induced hepatic glucose production in diabetic man but does not appear to be mediated by increased insulin secretion."}
{"id": "PMID:190075", "title": "Suppression of basal insulin secretion by adrenalin in normal man and in patients with insulinomas.", "content": "Basal insulin secretion has been thought to be via a different mechanism from stimulated insulin secretion, partly because it is not similarly suppressed by adrenalin. However, adrenalin normally causes hyperglycaemia, but if it is infused while the plasma glucose is kept constant there is marked suppression of insulin secretion. Sympathetic stimulation modulates basal insulin secretion, and alpha adrenergic blockade impaired the suppression of insulin secretion in response to hypoglycaemia. Four of five benign insulinomas had marked suppression of insulin secretion by adrenalin, but one malignant and one benign insulionoma had little suppression. Both had a raised proportion of their basal plasma insulin as proinsulin, and the impaired suppression of secretion by adrenalin probably signified an undifferentiated tumour.", "contents": "Suppression of basal insulin secretion by adrenalin in normal man and in patients with insulinomas. Basal insulin secretion has been thought to be via a different mechanism from stimulated insulin secretion, partly because it is not similarly suppressed by adrenalin. However, adrenalin normally causes hyperglycaemia, but if it is infused while the plasma glucose is kept constant there is marked suppression of insulin secretion. Sympathetic stimulation modulates basal insulin secretion, and alpha adrenergic blockade impaired the suppression of insulin secretion in response to hypoglycaemia. Four of five benign insulinomas had marked suppression of insulin secretion by adrenalin, but one malignant and one benign insulionoma had little suppression. Both had a raised proportion of their basal plasma insulin as proinsulin, and the impaired suppression of secretion by adrenalin probably signified an undifferentiated tumour."}
{"id": "PMID:190076", "title": "Effects of various modifiers of insulin release on the lanthanum-nondisplaceable 45Ca2+ uptake by isolated pancreatic islets.", "content": "The uptake of 45Ca2+ by a lanthanum-non-displaceable pool in pancreatic islets was studied; Raising the extracellular D-glucose concentration from 3 to 20 mM stimulated the 45Ca2+ uptake in hand-dissected islets of ob/bo-mice as well as in collagenase-isolated islets of ob/ob or normal mice. The effect was dose-dependent in the range of 0-20 mM D-glucose and was seen throughout a wide range of extracellular calcium concentrations (16 mumol-2.56 mmol of Ca2+ added per litre of medium). The 45Ca2+ uptake was also enhanced by other known insulin secretagogues (D-mannose, L-leucine, tolbutamide) and was uninfluenced by compounds lacking insulin-releasing capacity (3-O-methyl-D-glucose, L-glucose, D-galactose, D-leucine). The stimulatory effect of D-glucose was blocked by inhibitors of glucose-induced insulin release (D-mannoheptulose, diazoxide, L-adrenaline). The results support the view that the lanthanum-nondisplaceable calcium pool is related to the insulin-releasing mechanism, although the exact nature of this relationship is still unclear.", "contents": "Effects of various modifiers of insulin release on the lanthanum-nondisplaceable 45Ca2+ uptake by isolated pancreatic islets. The uptake of 45Ca2+ by a lanthanum-non-displaceable pool in pancreatic islets was studied; Raising the extracellular D-glucose concentration from 3 to 20 mM stimulated the 45Ca2+ uptake in hand-dissected islets of ob/bo-mice as well as in collagenase-isolated islets of ob/ob or normal mice. The effect was dose-dependent in the range of 0-20 mM D-glucose and was seen throughout a wide range of extracellular calcium concentrations (16 mumol-2.56 mmol of Ca2+ added per litre of medium). The 45Ca2+ uptake was also enhanced by other known insulin secretagogues (D-mannose, L-leucine, tolbutamide) and was uninfluenced by compounds lacking insulin-releasing capacity (3-O-methyl-D-glucose, L-glucose, D-galactose, D-leucine). The stimulatory effect of D-glucose was blocked by inhibitors of glucose-induced insulin release (D-mannoheptulose, diazoxide, L-adrenaline). The results support the view that the lanthanum-nondisplaceable calcium pool is related to the insulin-releasing mechanism, although the exact nature of this relationship is still unclear."}
{"id": "PMID:190077", "title": "Enhanced development of metastatic foci in thymectomized, irradiated, and bone marrow-reconstituted mice.", "content": "The effect of depletion of immunocompetence of metastasis of a mouse hepatoma MH-134 was studied in syngeneic C3H/He mice. (2) Development of metastasis in the lung and lymph nodes was remarkably enhanced in the mice which were thymectomized, irradiated, bone marrow-reconstituted (Tx-X-BM), and grafted intramuscularly with tumor cells. (2) Number of tumor cells detected in the blood stream was within the same range in the control mice and the Tx-X-BM mice after intramuscular tumor-grafting. (3) Metastatic foci were not detected in the stomach and intestines, not only in control mice but also in the Tx-X-BM mice after intramuscular tumor-grafting. However, tumors grew progressively in the subserosal tissues of these organs of the Tx-X-BM mice, but not of the control mice, when a small number of tumor cells were directly inoculated into such tissues. (4) On 9th day after an intravenous injection of a large number of tumor cells, tumor growth was detected to almost the same extent in the lungs of the control mice and the Tx-X-BM mice. Tumors grew progressively in the Tx-X-BM mice thereafter, whereas the tumors regressed in the control mice. These results suggest that inhibition of metastasis by immune response depends primarily upon suppression of proliferation of the tumor cells lodged in individual organs.", "contents": "Enhanced development of metastatic foci in thymectomized, irradiated, and bone marrow-reconstituted mice. The effect of depletion of immunocompetence of metastasis of a mouse hepatoma MH-134 was studied in syngeneic C3H/He mice. (2) Development of metastasis in the lung and lymph nodes was remarkably enhanced in the mice which were thymectomized, irradiated, bone marrow-reconstituted (Tx-X-BM), and grafted intramuscularly with tumor cells. (2) Number of tumor cells detected in the blood stream was within the same range in the control mice and the Tx-X-BM mice after intramuscular tumor-grafting. (3) Metastatic foci were not detected in the stomach and intestines, not only in control mice but also in the Tx-X-BM mice after intramuscular tumor-grafting. However, tumors grew progressively in the subserosal tissues of these organs of the Tx-X-BM mice, but not of the control mice, when a small number of tumor cells were directly inoculated into such tissues. (4) On 9th day after an intravenous injection of a large number of tumor cells, tumor growth was detected to almost the same extent in the lungs of the control mice and the Tx-X-BM mice. Tumors grew progressively in the Tx-X-BM mice thereafter, whereas the tumors regressed in the control mice. These results suggest that inhibition of metastasis by immune response depends primarily upon suppression of proliferation of the tumor cells lodged in individual organs."}
{"id": "PMID:190078", "title": "Estrogen receptor in breast cancer of the Japanese.", "content": "The estrogen receptor was assayed, using the 2,000g supernatant and dextran-coated charcoal method, in 243 tissue samples from human breast cancer, benign breast diseases, macroscopically normal breast tissues, normal uterine myometrium, and uterine myoma. The estrogen receptor was found to be positive in 52.1% of 98 primary breast cancer and in 54.1% of 24 metastatic tumors. The receptor in the breast cancer was found to be similar to that in normal uterine myometrium in the binding character; that is, the dissociation constant of 10(-9) approximately 10(-11) M and number of binding sites of 0 approximately 2,800 fmol/mg protein. There was no correlation between the presence of the receptor and some clinical factors such as menopausal status, age of the patient, urinary 17-ketosteroid excretion, clinical stage of cancer, tumor size, positive or negative axillary lymph node metastasis, histological type, metastatic site of the cancer, or disease-free interval. The estrogen receptor appeared to be retained by metastasis of cancer, and this may lead to the use of the receptor assay with mastectomy specimens for the prediction of response to hormonal therapy in future recurrence of malignancy. Furthermore, it may be possible by this assay to select patients suitable for adjuvant therapy with hormones at the time of mastectomy. A good correlation was found between the presence of the receptor and response to the major endocrine ablation therapy in patients with advanced or metastatic breast cancer. When the receptor was negative in the cancer tissue, the change of response to the endocrine therapy was minimum. On the other hand, if the cancer contained the receptor, approximately 60% of the patients with metastatic or advanced breast cancer responded well to the major endocrine ablation therapy. Thus, the estrogen receptor of breast cancer in Japanese patients appears to bear a close resemblance to that reported in Western patients in its incidence and the correlation to some biological characteristics of the cancer.", "contents": "Estrogen receptor in breast cancer of the Japanese. The estrogen receptor was assayed, using the 2,000g supernatant and dextran-coated charcoal method, in 243 tissue samples from human breast cancer, benign breast diseases, macroscopically normal breast tissues, normal uterine myometrium, and uterine myoma. The estrogen receptor was found to be positive in 52.1% of 98 primary breast cancer and in 54.1% of 24 metastatic tumors. The receptor in the breast cancer was found to be similar to that in normal uterine myometrium in the binding character; that is, the dissociation constant of 10(-9) approximately 10(-11) M and number of binding sites of 0 approximately 2,800 fmol/mg protein. There was no correlation between the presence of the receptor and some clinical factors such as menopausal status, age of the patient, urinary 17-ketosteroid excretion, clinical stage of cancer, tumor size, positive or negative axillary lymph node metastasis, histological type, metastatic site of the cancer, or disease-free interval. The estrogen receptor appeared to be retained by metastasis of cancer, and this may lead to the use of the receptor assay with mastectomy specimens for the prediction of response to hormonal therapy in future recurrence of malignancy. Furthermore, it may be possible by this assay to select patients suitable for adjuvant therapy with hormones at the time of mastectomy. A good correlation was found between the presence of the receptor and response to the major endocrine ablation therapy in patients with advanced or metastatic breast cancer. When the receptor was negative in the cancer tissue, the change of response to the endocrine therapy was minimum. On the other hand, if the cancer contained the receptor, approximately 60% of the patients with metastatic or advanced breast cancer responded well to the major endocrine ablation therapy. Thus, the estrogen receptor of breast cancer in Japanese patients appears to bear a close resemblance to that reported in Western patients in its incidence and the correlation to some biological characteristics of the cancer."}
{"id": "PMID:190079", "title": "Depression of multinucleation by interferon in simian virus 40-transformed cells treated with cytochalasin-B.", "content": "Multinucleation of simian virus 40-transformed mouse cells (mKS-A TU-7), which was induced by Cytochalasin-B, was depressed by the addition of crude interferon or by poly (riboinosinic)-poly(ribocytidylic) acid. In the absence of Cytochalasin-B, growth of the cells was not inhibited by interferon. Possible mechanism of this phenomenon is discussed.", "contents": "Depression of multinucleation by interferon in simian virus 40-transformed cells treated with cytochalasin-B. Multinucleation of simian virus 40-transformed mouse cells (mKS-A TU-7), which was induced by Cytochalasin-B, was depressed by the addition of crude interferon or by poly (riboinosinic)-poly(ribocytidylic) acid. In the absence of Cytochalasin-B, growth of the cells was not inhibited by interferon. Possible mechanism of this phenomenon is discussed."}
{"id": "PMID:190080", "title": "Disseminated cytomegalic inclusion disease in an adult with cirrhosis of liver and review of literatures.", "content": "We reported a 44 year old man with micronodular cirrhosis who eventually died from massive hematemesis and melena. At postmortem studies, there were disseminated cytomegalic inclusion bodies detected in various organs. In liver, intranuclear inclusion bodies were observed in cirrhotic liver. We discussed here possible pathogenesis of CMV (cytomegalovirus) infection in adults, in reviewing literatures.", "contents": "Disseminated cytomegalic inclusion disease in an adult with cirrhosis of liver and review of literatures. We reported a 44 year old man with micronodular cirrhosis who eventually died from massive hematemesis and melena. At postmortem studies, there were disseminated cytomegalic inclusion bodies detected in various organs. In liver, intranuclear inclusion bodies were observed in cirrhotic liver. We discussed here possible pathogenesis of CMV (cytomegalovirus) infection in adults, in reviewing literatures."}
{"id": "PMID:190081", "title": "Structure-activity relationships of gastrointestinal hormones: motilin, GIP, and [27-TYR]CCK-PZ.", "content": "The docosapeptide and the tritetracontapeptide corresponding to the entire amino acid sequence of porcine motilin and gastric inhibitory peptide were synthesized, and in addition, an unsulfated form of cholecystokinin-pancreozymin (CCK-PZ) was prepared to cast some light on the structure-activity relationships of these gastrointestinal hormones. In a series of motilin peptides, elimination of the pentapeptide from the amino terminus decreased the activity (in vitro contraction of rabbit duodenal muscle) to 1/250 of the whole molecule, and subsequent removal of the tripeptide Thr-Tyr-Gly resulted in the complete loss of its effects, In a series of gastric inhibitory peptides, two fragments corresponding to positions 1 to 28 and 26 to 43 were both inactive. However, the nonacosapeptide (15 to 43) retained one-fourth of the activity of the tritetracontapeptide (suppression of the gastric acid secretion stimulated by tetragastrin in Heidenhain pouch dogs). Synthetic [27-Tyr]CCK-PZ exhibited 1/250 of the activity of natural CCK-PZ (amylase release from rat pancreas). This compound was smoothly and efficiently labeled with 125I (specific activity 200 to 250 muc per mug).", "contents": "Structure-activity relationships of gastrointestinal hormones: motilin, GIP, and [27-TYR]CCK-PZ. The docosapeptide and the tritetracontapeptide corresponding to the entire amino acid sequence of porcine motilin and gastric inhibitory peptide were synthesized, and in addition, an unsulfated form of cholecystokinin-pancreozymin (CCK-PZ) was prepared to cast some light on the structure-activity relationships of these gastrointestinal hormones. In a series of motilin peptides, elimination of the pentapeptide from the amino terminus decreased the activity (in vitro contraction of rabbit duodenal muscle) to 1/250 of the whole molecule, and subsequent removal of the tripeptide Thr-Tyr-Gly resulted in the complete loss of its effects, In a series of gastric inhibitory peptides, two fragments corresponding to positions 1 to 28 and 26 to 43 were both inactive. However, the nonacosapeptide (15 to 43) retained one-fourth of the activity of the tritetracontapeptide (suppression of the gastric acid secretion stimulated by tetragastrin in Heidenhain pouch dogs). Synthetic [27-Tyr]CCK-PZ exhibited 1/250 of the activity of natural CCK-PZ (amylase release from rat pancreas). This compound was smoothly and efficiently labeled with 125I (specific activity 200 to 250 muc per mug)."}
{"id": "PMID:190084", "title": "Role of DNA sequences in genetic recombination in the iso-1-cytochrome c gene of yeast. II. Comparison of mutants altered at the same and nearby base pairs.", "content": "X-ray-induced mitotic recombination rates and spontaneous meiotic recombination rates have been determined in two-point crosses of various defined cyc1 mutants of the yeast Saccharomyces cerevisiae. All but one of the 17 cyc1 mutants chosen for this study contained either the addition, deletion or substitution of single base-pairs located within a defined segment of the gene that corresponds to the 11 amino acid residues at the amino terminus of iso-1-cytochrome c; approximately half of these mutants had alterations of the AUG initiation codon, some at the same base pair. Up to 66-fold differences in X-ray-induced recombination rates were observed when the same cyc1 mutant was crossed to cyc1 mutants having different alterations in the AUG initiation codon; over a ten-fold difference was observed in series of homologous crosses involving mutants with different changes at the same base-pair. Recombination rates that were associated with specific cyc1 mutants co-segregated with the particular alleles following meiosis, and comparable recombination patterns were also observed for independently isolated, identical mutations. With the mutants used in this study, the frequencies of meiotic recombination did not differ as markedly, suggesting a dissimilar dependence on specific DNA sequences for these two modes of recombination. These disproportionalities of recombination rates suggest that the nature of the mismatched bases influences the recombination process, but not in a way that can be simply interpreted.", "contents": "Role of DNA sequences in genetic recombination in the iso-1-cytochrome c gene of yeast. II. Comparison of mutants altered at the same and nearby base pairs. X-ray-induced mitotic recombination rates and spontaneous meiotic recombination rates have been determined in two-point crosses of various defined cyc1 mutants of the yeast Saccharomyces cerevisiae. All but one of the 17 cyc1 mutants chosen for this study contained either the addition, deletion or substitution of single base-pairs located within a defined segment of the gene that corresponds to the 11 amino acid residues at the amino terminus of iso-1-cytochrome c; approximately half of these mutants had alterations of the AUG initiation codon, some at the same base pair. Up to 66-fold differences in X-ray-induced recombination rates were observed when the same cyc1 mutant was crossed to cyc1 mutants having different alterations in the AUG initiation codon; over a ten-fold difference was observed in series of homologous crosses involving mutants with different changes at the same base-pair. Recombination rates that were associated with specific cyc1 mutants co-segregated with the particular alleles following meiosis, and comparable recombination patterns were also observed for independently isolated, identical mutations. With the mutants used in this study, the frequencies of meiotic recombination did not differ as markedly, suggesting a dissimilar dependence on specific DNA sequences for these two modes of recombination. These disproportionalities of recombination rates suggest that the nature of the mismatched bases influences the recombination process, but not in a way that can be simply interpreted."}
{"id": "PMID:190088", "title": "Studies on viremia and antibody formation in ducklings and goslings after experimental infection with Lednice (Yaba 1) virus.", "content": "A very low virus level was found for a short time in the blood of ducklings and goslings after experimental Lednice (Yaba 1) virus infection by subcutaneous (scut) and intranasal (inas) route and in blood of ducklings also after infection by intracerebral (icer) route. Subsequently virus neutralizing antibody formation was examined. Antibody formation was found in most of animals. In goslings onset of antibody formation seems to be slower than in ducklings after the same virus infection dose; vice versa, in ducklings antibody titer decreased after 6 weeks. Using low infection virus dose, neutralizing antibody level in ducklings was lower than in the former case. On examining the blood and the organs, the virus was detected in a very low amount and for a very short time in blood and spleen of goslings and only in blood of ducklings.", "contents": "Studies on viremia and antibody formation in ducklings and goslings after experimental infection with Lednice (Yaba 1) virus. A very low virus level was found for a short time in the blood of ducklings and goslings after experimental Lednice (Yaba 1) virus infection by subcutaneous (scut) and intranasal (inas) route and in blood of ducklings also after infection by intracerebral (icer) route. Subsequently virus neutralizing antibody formation was examined. Antibody formation was found in most of animals. In goslings onset of antibody formation seems to be slower than in ducklings after the same virus infection dose; vice versa, in ducklings antibody titer decreased after 6 weeks. Using low infection virus dose, neutralizing antibody level in ducklings was lower than in the former case. On examining the blood and the organs, the virus was detected in a very low amount and for a very short time in blood and spleen of goslings and only in blood of ducklings."}
{"id": "PMID:190089", "title": "Activities of mitochondrial enzymes during aerobic synchronous growth of aerobically and anaerobically grown Saccharomyces cerevisiae.", "content": "The mitochondrial enzymes cytochrome-c:O2-oxidoreductase (E.C.1.9.3.1), NADH:cytochrome-c-oxidoreductase (E.C.1.6.2.1), NADH: ferricyanide oxidoreductase (E.C.1.6.2.99), L-malate hydrolase (E.C.4.2.1.2) and L-malate:NADH-oxidoreductase (E.C.1.1.3.7) increase their activities during the aerobic synchronous growth of aerobically grown Saccharomyces cerevisiae in discrete steps and only once during the cell cycle. An identical phenomenon was observed during the aerobic synchronous growth of anaerobically grown yeast. The mechanism of completization of mitochondrial membranes is thus likely to be discontinuous and the same during both mitochondrial multiplication and the conversion of promitochondria to fully functioning mitochondria.", "contents": "Activities of mitochondrial enzymes during aerobic synchronous growth of aerobically and anaerobically grown Saccharomyces cerevisiae. The mitochondrial enzymes cytochrome-c:O2-oxidoreductase (E.C.1.9.3.1), NADH:cytochrome-c-oxidoreductase (E.C.1.6.2.1), NADH: ferricyanide oxidoreductase (E.C.1.6.2.99), L-malate hydrolase (E.C.4.2.1.2) and L-malate:NADH-oxidoreductase (E.C.1.1.3.7) increase their activities during the aerobic synchronous growth of aerobically grown Saccharomyces cerevisiae in discrete steps and only once during the cell cycle. An identical phenomenon was observed during the aerobic synchronous growth of anaerobically grown yeast. The mechanism of completization of mitochondrial membranes is thus likely to be discontinuous and the same during both mitochondrial multiplication and the conversion of promitochondria to fully functioning mitochondria."}
{"id": "PMID:190090", "title": "Cardiolipin synthesis during the cell cycle of the yeast Saccharomyces cervisiae.", "content": "Cardiolipin synthesis was studied during the aerobic synchronous growth of aerobically grown yeast Saccharomyces cerevisiae. The time course of the synthesis was stepwise and the rise in cardiolipin level in cells coincided in time with the increase in cytochrome oxidase activity. This finding supports the notion of discontinuous completion of the inner mitochondrial membrane and hints at a close relation between cardiolipin and cytochrome oxidase activity.", "contents": "Cardiolipin synthesis during the cell cycle of the yeast Saccharomyces cervisiae. Cardiolipin synthesis was studied during the aerobic synchronous growth of aerobically grown yeast Saccharomyces cerevisiae. The time course of the synthesis was stepwise and the rise in cardiolipin level in cells coincided in time with the increase in cytochrome oxidase activity. This finding supports the notion of discontinuous completion of the inner mitochondrial membrane and hints at a close relation between cardiolipin and cytochrome oxidase activity."}
{"id": "PMID:190091", "title": "Effect of iron-beryllium antagonism on the growth of Pseudomonas fluorescens type S.", "content": "Studies of the growth of Pseudomonas fluorescens type S in acidified peptone nutrient broth supplemented with potassium dioxalatoberyllate show that the inhibitory action of beryllium on the lag phase can be strongly counteracted by an increase in the iron content of the medium. In terms of relative concentrations, Fe3+ is up to 250 times more effective than Mg2+ as an antagonist of beryllium under the conditions employed. Conversely, evidence of the effect of beryllium on iron-dependent constituents of the cell is provided by the fact that cultures of Pseudomonas fluorescens adapted to relatively high concentrations of beryllium show a marked decrease in cytochrome c content.", "contents": "Effect of iron-beryllium antagonism on the growth of Pseudomonas fluorescens type S. Studies of the growth of Pseudomonas fluorescens type S in acidified peptone nutrient broth supplemented with potassium dioxalatoberyllate show that the inhibitory action of beryllium on the lag phase can be strongly counteracted by an increase in the iron content of the medium. In terms of relative concentrations, Fe3+ is up to 250 times more effective than Mg2+ as an antagonist of beryllium under the conditions employed. Conversely, evidence of the effect of beryllium on iron-dependent constituents of the cell is provided by the fact that cultures of Pseudomonas fluorescens adapted to relatively high concentrations of beryllium show a marked decrease in cytochrome c content."}
{"id": "PMID:190092", "title": "Dependence of yeast sporulation on mitochondrial protein synthesis.", "content": "Sporulation in diploid Saccharomyces cerevisiae is not dependent on continued protein synthesis in the mitochondria. Using chloramphenicol, it is shown that proteins essential for respiration and sporulation are synthesized in mitochondria early during growth in a presporulation medium.", "contents": "Dependence of yeast sporulation on mitochondrial protein synthesis. Sporulation in diploid Saccharomyces cerevisiae is not dependent on continued protein synthesis in the mitochondria. Using chloramphenicol, it is shown that proteins essential for respiration and sporulation are synthesized in mitochondria early during growth in a presporulation medium."}
{"id": "PMID:190093", "title": "Eye movements during transcendental meditation.", "content": "Characteristic changes in eye movements occurred during meditation with closed eyes in a proportion of subjects experienced in TM. The most common changes were an increase in slow, large-amplitude, 'rolling' eye movements and a concomitant decrease in rapid, low-amplitude, 'jerky' eye movements. Much variation occurred between individuals, however, some subjects showing no differences between TM and non-meditation. Any changes that occurred were not necessarily constant for the whole recording period nor consistent between sessions. The physiological effects of TM are far more variable than previously publicized. In general, the main changes in eye movements during TM are similar to those during passive hypnosis.", "contents": "Eye movements during transcendental meditation. Characteristic changes in eye movements occurred during meditation with closed eyes in a proportion of subjects experienced in TM. The most common changes were an increase in slow, large-amplitude, 'rolling' eye movements and a concomitant decrease in rapid, low-amplitude, 'jerky' eye movements. Much variation occurred between individuals, however, some subjects showing no differences between TM and non-meditation. Any changes that occurred were not necessarily constant for the whole recording period nor consistent between sessions. The physiological effects of TM are far more variable than previously publicized. In general, the main changes in eye movements during TM are similar to those during passive hypnosis."}
{"id": "PMID:190095", "title": "[To the differential diagnosis of bronchiolo-alveolar-cell carcinoma in early state (author's transl)].", "content": "Prompt surgical treatment of the solitary form of bronchiolo-alveolar-cell carcinoma offers a good survival rate in comparison with bronchogenic carcinoma; the prognosis of the diffuse form is poor. Review of 28 cases of solitary BAC showed an airbronchogram in 36% and a tail sign in 85% of cases; both features were found in 32% of tumors. The air bronchogram seems to be specific for this type of tumours, the tail sign is found with granulomatous or inflammatory diseases as well. In the differential diagnosis of a peripheral coin lesion with air bronchogramm and tail sign, without calcifications and atelectasis, a BAC should be taken into serious consideration.", "contents": "[To the differential diagnosis of bronchiolo-alveolar-cell carcinoma in early state (author's transl)]. Prompt surgical treatment of the solitary form of bronchiolo-alveolar-cell carcinoma offers a good survival rate in comparison with bronchogenic carcinoma; the prognosis of the diffuse form is poor. Review of 28 cases of solitary BAC showed an airbronchogram in 36% and a tail sign in 85% of cases; both features were found in 32% of tumors. The air bronchogram seems to be specific for this type of tumours, the tail sign is found with granulomatous or inflammatory diseases as well. In the differential diagnosis of a peripheral coin lesion with air bronchogramm and tail sign, without calcifications and atelectasis, a BAC should be taken into serious consideration."}
{"id": "PMID:190096", "title": "[Determination of autohemolysin formation using the plaque test. Demonstration of autoimmune phenomena following vaccinations and infections].", "content": "A simple and sensitive modification of the plaque assay for the evaluation of autohaemolysin-producing cells (APC) in the peripheral blood is described: Very small chambers, (volume less than or equal to 0.03 cc) made out of glass slides (75 X 25 mm), are filled with a diluted (1:7) blood cell suspension. After incubation for 26 hours the haemolytic plaques produced by APC in the thin monolayer of blood cells can be counted under the microcope at a magnification up to 320-fold. The number of APC in guinea pigs immunized with cholera vaccine and in monkeys infected with variola-virus was evaluated by means of this method. Cholera vaccination significantly raised the APC up to 7 days after immunization. In monkeys these cells increased markedly between 4 and 7 days after infection with variola-virus. The increase was less pronounced in animals partially protected by prior vaccination with attenuated vaccinia-virus (MVA-strain) and showing a mild course of variola. Autoimmune mechanisms may exist in apparently normal organisms. They may rise after tissue destruction or cell alteration by infectious or other exogenous agents. The method described might be useful to determine the degree of reactogenicity of bacterial and viral vaccines.", "contents": "[Determination of autohemolysin formation using the plaque test. Demonstration of autoimmune phenomena following vaccinations and infections]. A simple and sensitive modification of the plaque assay for the evaluation of autohaemolysin-producing cells (APC) in the peripheral blood is described: Very small chambers, (volume less than or equal to 0.03 cc) made out of glass slides (75 X 25 mm), are filled with a diluted (1:7) blood cell suspension. After incubation for 26 hours the haemolytic plaques produced by APC in the thin monolayer of blood cells can be counted under the microcope at a magnification up to 320-fold. The number of APC in guinea pigs immunized with cholera vaccine and in monkeys infected with variola-virus was evaluated by means of this method. Cholera vaccination significantly raised the APC up to 7 days after immunization. In monkeys these cells increased markedly between 4 and 7 days after infection with variola-virus. The increase was less pronounced in animals partially protected by prior vaccination with attenuated vaccinia-virus (MVA-strain) and showing a mild course of variola. Autoimmune mechanisms may exist in apparently normal organisms. They may rise after tissue destruction or cell alteration by infectious or other exogenous agents. The method described might be useful to determine the degree of reactogenicity of bacterial and viral vaccines."}
{"id": "PMID:190099", "title": "[Ovarian metastases in breast carcinoma].", "content": "The effect on prognosis of the presence of ovarian metastases was studied in patients oophorectomized in treatment of progressive breast cancer. At laparotomy, 28% (n = 42) were found to have ovarian metastases. This high percentage indicates that cases studied were in a relatively progressed state. In the cases with ovarian metastases, the clinical course of the disease was no different to those histologically free from metastases. It appears therefore that the presence of secondary ovarian metastases at oophorectomy is of no therapeutic or prognostic significance. The time interval between oophorectomy and mastectomy, however, apparently does have a bearing on the progress of the disease.", "contents": "[Ovarian metastases in breast carcinoma]. The effect on prognosis of the presence of ovarian metastases was studied in patients oophorectomized in treatment of progressive breast cancer. At laparotomy, 28% (n = 42) were found to have ovarian metastases. This high percentage indicates that cases studied were in a relatively progressed state. In the cases with ovarian metastases, the clinical course of the disease was no different to those histologically free from metastases. It appears therefore that the presence of secondary ovarian metastases at oophorectomy is of no therapeutic or prognostic significance. The time interval between oophorectomy and mastectomy, however, apparently does have a bearing on the progress of the disease."}
{"id": "PMID:190100", "title": "[Cyclic adenosine monophosphate, prostaglandin E and aggregation of blood platelets in man].", "content": "The relationship of cyclic AMP to platelet function has been examined directly by assay of the platelet content of the nucleotide and platelet aggregation. Platelet aggregation is favored by an decrease in platelet cyclic AMP and inhibited by an increase in cyclic AMP. The platelet aggregation is accompanied by reduction in cyclic AMP. beta adrenergic substances increase platelet cyclic AMP in vivo and simultaneously block platelet aggregation. Thrombin selectively causes human platelets to form and release PGE. The amount formed was proportional to the amount of thrombin added and high enough to influence platelet aggregation in vitro. Platelet prostaglandin formation by washed platelets and platelet-rich plasma was not proportional to the degree of platelet aggregation induced by stirring. We were unable to detect PGE-formation in response to ADP. Thrombin-induced synthesis of PGE is inhibited by ADP. Aspirin selectively inhibits PGE-production in human platelets. This reaction does not depend on the extend of platelet aggregation. These studies suggest that cyclic AMP is the key to regulation of platelet aggregation and that PGE, formed by platelets, through its effects on cyclic AMP may play a role in regulating platelet aggregation.", "contents": "[Cyclic adenosine monophosphate, prostaglandin E and aggregation of blood platelets in man]. The relationship of cyclic AMP to platelet function has been examined directly by assay of the platelet content of the nucleotide and platelet aggregation. Platelet aggregation is favored by an decrease in platelet cyclic AMP and inhibited by an increase in cyclic AMP. The platelet aggregation is accompanied by reduction in cyclic AMP. beta adrenergic substances increase platelet cyclic AMP in vivo and simultaneously block platelet aggregation. Thrombin selectively causes human platelets to form and release PGE. The amount formed was proportional to the amount of thrombin added and high enough to influence platelet aggregation in vitro. Platelet prostaglandin formation by washed platelets and platelet-rich plasma was not proportional to the degree of platelet aggregation induced by stirring. We were unable to detect PGE-formation in response to ADP. Thrombin-induced synthesis of PGE is inhibited by ADP. Aspirin selectively inhibits PGE-production in human platelets. This reaction does not depend on the extend of platelet aggregation. These studies suggest that cyclic AMP is the key to regulation of platelet aggregation and that PGE, formed by platelets, through its effects on cyclic AMP may play a role in regulating platelet aggregation."}
{"id": "PMID:190102", "title": "Use of highly specific antibodies against 17alpha-OH-progesterone in a simplified nonchromatographic RIA and in the simultaneous determination of four sex hormones in human plasma.", "content": "A highly specific antiserum raised against the 3(O-carboxymethyl)oxime of 17alpha-hydroxyprogesterone (17-OHP) was produced in rabbit and used in the development of a specific radioimmunoassay (RIA) for 17-OHP which included a celite chromatography. Methods allowing the measurement of plasma 17-OHP levels either separately or in combination with that of several plasma androgens (testosterone, delta4-androstenedione and dehydroepiandrosterone) are described. Moreover, RIA meabsurement of plasma 17-OHP levels with or without chromatographic (celite column) purification gave comparable results (mean +/- SD) in 29 normal adult males (118 +/- 34 ng/100 ml) and 35 normal adult females (follicular phase: 46+/- 16 ng/100 ml); luteal phase: 241 +/- 71 ng/100 ml).", "contents": "Use of highly specific antibodies against 17alpha-OH-progesterone in a simplified nonchromatographic RIA and in the simultaneous determination of four sex hormones in human plasma. A highly specific antiserum raised against the 3(O-carboxymethyl)oxime of 17alpha-hydroxyprogesterone (17-OHP) was produced in rabbit and used in the development of a specific radioimmunoassay (RIA) for 17-OHP which included a celite chromatography. Methods allowing the measurement of plasma 17-OHP levels either separately or in combination with that of several plasma androgens (testosterone, delta4-androstenedione and dehydroepiandrosterone) are described. Moreover, RIA meabsurement of plasma 17-OHP levels with or without chromatographic (celite column) purification gave comparable results (mean +/- SD) in 29 normal adult males (118 +/- 34 ng/100 ml) and 35 normal adult females (follicular phase: 46+/- 16 ng/100 ml); luteal phase: 241 +/- 71 ng/100 ml)."}
{"id": "PMID:190103", "title": "Protein synthesis in postnuclear supernatants from mengovirus-infected Ehrlich ascites tumor cells.", "content": "The effect of mengovirus infection on the protein synthetic capacity of Ehrlich ascites tumor cells cultured in vitro was studied in vivo and in vitro employing postnuclear supernatants prepared at various times post-infection in the absence and in the presence of 1% Triton X-100. The amino acid incorporating activities of extracts obtained in the presence of the detergent were reduced by about 30% compared with the capacities of the corresponding postnuclear supernatants prepared in the absence of Triton X-100; but the course of the activity vs. time curve was not influenced by the detergent. Under the conditions employed, the postnuclear supernatants were unable to reinitiate protein synthesis once elongation of nascent polypeptide chains concomitant with ribosome runoff was completed. After mengovirus infection, a gradual disappearance of polysomes from postnuclear supernatants and a simultaneous accumulation of monosomes was observed. The protein-synthesizing activities of normal and infected cells were inversely proportional to the monosome concentrations of their corresponding extracts. Qualitatively, protein synthesis in intact cells and in postnuclear supernatants responded similarly to mengovirus infection. In both cases an initial reduction of host-specific amino acid incorporation was followed by a burst of viral protein synthesis. However, the two activity vs. time curves showed the following significant differences: 1) The activities of extracts from control cells and from mengovirus-infected cells nearly in the infectious cycle were low compared with the activities observed in vivo. 2) In the middle of the infectious cycle, the peak of viral protein synthesis occurred later and the activity was higher in vitro. 3) Finally, in the late period of the infectious cycle the postnuclear supernatants had considerable protein synthesizing activity, at a time when protein synthesis in vivo was nil.", "contents": "Protein synthesis in postnuclear supernatants from mengovirus-infected Ehrlich ascites tumor cells. The effect of mengovirus infection on the protein synthetic capacity of Ehrlich ascites tumor cells cultured in vitro was studied in vivo and in vitro employing postnuclear supernatants prepared at various times post-infection in the absence and in the presence of 1% Triton X-100. The amino acid incorporating activities of extracts obtained in the presence of the detergent were reduced by about 30% compared with the capacities of the corresponding postnuclear supernatants prepared in the absence of Triton X-100; but the course of the activity vs. time curve was not influenced by the detergent. Under the conditions employed, the postnuclear supernatants were unable to reinitiate protein synthesis once elongation of nascent polypeptide chains concomitant with ribosome runoff was completed. After mengovirus infection, a gradual disappearance of polysomes from postnuclear supernatants and a simultaneous accumulation of monosomes was observed. The protein-synthesizing activities of normal and infected cells were inversely proportional to the monosome concentrations of their corresponding extracts. Qualitatively, protein synthesis in intact cells and in postnuclear supernatants responded similarly to mengovirus infection. In both cases an initial reduction of host-specific amino acid incorporation was followed by a burst of viral protein synthesis. However, the two activity vs. time curves showed the following significant differences: 1) The activities of extracts from control cells and from mengovirus-infected cells nearly in the infectious cycle were low compared with the activities observed in vivo. 2) In the middle of the infectious cycle, the peak of viral protein synthesis occurred later and the activity was higher in vitro. 3) Finally, in the late period of the infectious cycle the postnuclear supernatants had considerable protein synthesizing activity, at a time when protein synthesis in vivo was nil."}
{"id": "PMID:190104", "title": "Lipid-protein interactions between human apolipoprotein A-I and defined sphingomyelin species. A 13C-NMR spectroscopic study.", "content": "Chromatographyically and immunologically homogeneous apolipoprotein A-I (apoLp A-I) from human serum has been recombined in separate experiments with three species of sphingomyelin. The differed in the degree of saturation of their fatty acyl residues, stearoyl (18:0), oleoyl (18:1) and linoleoyl (18:2). The lipoprotein complexes formed were purified by CsCl density gradient centrifugation between 1.07 - 1.09 g/cm3 and by gel filtration. Stearoylsphingomyelin does not recombine with the apoprotein A-I below its phase transition temperature (tc = 41.5 degrees C). The lipoproteins eluted with the following apparent molecular weights: 18:0-sphingomyelin apoLp A-I, 8.0 X 10(5); 18:1-sphingomyelin apoLp A-I, 4.0 X 10(5); and 18:2-sphingomyelin apoLp A-I, 4.0 X 10(5). In electron microscopy the particles appear as discs of 160 - 170 A diameter and 50 - 60 A thickness. Their tendency to form stacked aggregates of discs decreases with the degree of their unsaturation. CD measurements underline the considerable increase in alpha-helicity of the secondary structure of apo A-I after recombination with the phospholipids. This increase in order is equal for the three sphingomyelin species (alpha-helicity of apoLP A-I = 0.46, after recombination 0.89). If the three sphingomyelin species are used in equal molar amounts in the recombination experiment, no preference for any one sphingomyelin species is observed. Recombination of apoLp A-I with sphingomyelin, labelled with the isotope 13C in the choline group, C-14 of stearic or linoleic, or C-11 of oleic acid, were performed for spin lattice relaxation time (T1) experiments. Compared with sphingomyelin liposomes, the polar head groups of these lipids in the lipoprotein particles possess a considerably higher mobility, whereas the changes in T-1-times of the C-atoms in the centre of the fatty acid chains of the lipids refer to their interactions with the polypeptide side chains. A model of the lipoprotein complexes formed is proposed on the basis of the experimental data.", "contents": "Lipid-protein interactions between human apolipoprotein A-I and defined sphingomyelin species. A 13C-NMR spectroscopic study. Chromatographyically and immunologically homogeneous apolipoprotein A-I (apoLp A-I) from human serum has been recombined in separate experiments with three species of sphingomyelin. The differed in the degree of saturation of their fatty acyl residues, stearoyl (18:0), oleoyl (18:1) and linoleoyl (18:2). The lipoprotein complexes formed were purified by CsCl density gradient centrifugation between 1.07 - 1.09 g/cm3 and by gel filtration. Stearoylsphingomyelin does not recombine with the apoprotein A-I below its phase transition temperature (tc = 41.5 degrees C). The lipoproteins eluted with the following apparent molecular weights: 18:0-sphingomyelin apoLp A-I, 8.0 X 10(5); 18:1-sphingomyelin apoLp A-I, 4.0 X 10(5); and 18:2-sphingomyelin apoLp A-I, 4.0 X 10(5). In electron microscopy the particles appear as discs of 160 - 170 A diameter and 50 - 60 A thickness. Their tendency to form stacked aggregates of discs decreases with the degree of their unsaturation. CD measurements underline the considerable increase in alpha-helicity of the secondary structure of apo A-I after recombination with the phospholipids. This increase in order is equal for the three sphingomyelin species (alpha-helicity of apoLP A-I = 0.46, after recombination 0.89). If the three sphingomyelin species are used in equal molar amounts in the recombination experiment, no preference for any one sphingomyelin species is observed. Recombination of apoLp A-I with sphingomyelin, labelled with the isotope 13C in the choline group, C-14 of stearic or linoleic, or C-11 of oleic acid, were performed for spin lattice relaxation time (T1) experiments. Compared with sphingomyelin liposomes, the polar head groups of these lipids in the lipoprotein particles possess a considerably higher mobility, whereas the changes in T-1-times of the C-atoms in the centre of the fatty acid chains of the lipids refer to their interactions with the polypeptide side chains. A model of the lipoprotein complexes formed is proposed on the basis of the experimental data."}
{"id": "PMID:190107", "title": "Hormonal influences on motivation, learning, and memory processes.", "content": "Experiments have shown that the hypothalamic, pituitary, and adrenocortical hormones play an important role in the motivational value of environmental cues, in the acquisition of knowledge, and in the long-term memory of learned behavior. In human volunteers, a synthetic fraction of ACTH seems to improve visual memory, enhance alertness, and increase motivation--all without the hormone's usual endocrine effects.", "contents": "Hormonal influences on motivation, learning, and memory processes. Experiments have shown that the hypothalamic, pituitary, and adrenocortical hormones play an important role in the motivational value of environmental cues, in the acquisition of knowledge, and in the long-term memory of learned behavior. In human volunteers, a synthetic fraction of ACTH seems to improve visual memory, enhance alertness, and increase motivation--all without the hormone's usual endocrine effects."}
{"id": "PMID:190109", "title": "Options for care of the aged sick.", "content": "Hospital workups should be done only when they will produce information not otherwise obtainable. Even when patients are acutely ill, home care may be preferable; after care and day care are often best for long-term treatment.", "contents": "Options for care of the aged sick. Hospital workups should be done only when they will produce information not otherwise obtainable. Even when patients are acutely ill, home care may be preferable; after care and day care are often best for long-term treatment."}
{"id": "PMID:190110", "title": "Diagnosis and management of congenital adrenal hyperplasia.", "content": "After a generation of appropriately treated patients, it is now clear that most of those affected with congenital adrenal hyperplasia can lead virtually normal lives, in terms of ultimate height and sexual development. But the key is early diagnosis. The underlying biochemical mechanisms in the various forms of the disease are discussed, together with the principles and specifics of adrenal hormone replacement therapy.", "contents": "Diagnosis and management of congenital adrenal hyperplasia. After a generation of appropriately treated patients, it is now clear that most of those affected with congenital adrenal hyperplasia can lead virtually normal lives, in terms of ultimate height and sexual development. But the key is early diagnosis. The underlying biochemical mechanisms in the various forms of the disease are discussed, together with the principles and specifics of adrenal hormone replacement therapy."}
{"id": "PMID:190114", "title": "Latent genomes of Epstein-Barr virus.", "content": "Of the EBV DNAs in Raji cells that contained 50 to 60 viral genomes per cell, 90% were separated from high molecular weight cellular DNA by centrifugation in a neutral glycerol gradient after lysis of the cells by treatment with pronase and Sarkosyl, indicating that the major portion of the EBV DNA in Raji cells was not integrated linearly into cellular DNA.", "contents": "Latent genomes of Epstein-Barr virus. Of the EBV DNAs in Raji cells that contained 50 to 60 viral genomes per cell, 90% were separated from high molecular weight cellular DNA by centrifugation in a neutral glycerol gradient after lysis of the cells by treatment with pronase and Sarkosyl, indicating that the major portion of the EBV DNA in Raji cells was not integrated linearly into cellular DNA."}
{"id": "PMID:190116", "title": "Structure and function of herpesvirus saimira DNA.", "content": "Two types of genomes are present in HVS stocks: (1) the defective H-genome consisting of highly reiterated heavy (71% C+G) sequences; and (2) the M-genome, which carries the whole genetic information of HVS and is infectious in tissue culture. The sequences in the M-genome are made up of 70% unique L-DNA (with 36% C + G) and 30% H-DNA, which is highly repetitive. H-sequences in the M-genome are clustered at the ends of the molecule.", "contents": "Structure and function of herpesvirus saimira DNA. Two types of genomes are present in HVS stocks: (1) the defective H-genome consisting of highly reiterated heavy (71% C+G) sequences; and (2) the M-genome, which carries the whole genetic information of HVS and is infectious in tissue culture. The sequences in the M-genome are made up of 70% unique L-DNA (with 36% C + G) and 30% H-DNA, which is highly repetitive. H-sequences in the M-genome are clustered at the ends of the molecule."}
{"id": "PMID:190126", "title": "Nucleic acid biosynthesis in nuclei of cell infected with herpesviruses (HSV and EBV).", "content": "Analysis of nuclei isolated from herpes simplex virus (HSV)-infected cells by electrophoresis in polyacrylamide gels showed that only virion-associated DNA molecules migrated into the gels. The viral DNA molecules, which do not migrate in the gels, are the precursors for the mature viral DNA. Centrifugation of deoxycholate-treated infected nuclei in sucrose gradients revealed that most of the viral DNA co-sedimented with the cellular DNA. The DNA-dependent RNA polymerase activity also co-sedimented with the viral and cellular DNA. Incubation of nuclei isolated from HSV-infected cells, under in vitro conditions that support DNA synthesis, resulted in the synthesis of viral molecules of low molecular weight. Under the same conditions, nuclei from Burkitt lymphoblasts did not synthesize DNA. The nature of the association between cellular DNA and EBV DNA was studied by hybridization with EBV cRNA. EBV-specific sequences were found in the lymphoblast DNA; they banded at a density of 1.707 g/cm3. Some of the viral mRNA transcribed in HSV-infected nuclei is symmetrically transcribed from HSV DNA. The symmetrical portions of the RNA are removed, since poly (A)-containing mRNA molecules lack homologous sequences. Most of the RNA synthesized in HSV-infected nuclei can be released after incubation of the nuclei in vitro in the presence of ATP. The released RNA consists of poly(A)plus and poly (A)-minus molecules. The mechanism of RNA transport from the nuclei still remains to be studied.", "contents": "Nucleic acid biosynthesis in nuclei of cell infected with herpesviruses (HSV and EBV). Analysis of nuclei isolated from herpes simplex virus (HSV)-infected cells by electrophoresis in polyacrylamide gels showed that only virion-associated DNA molecules migrated into the gels. The viral DNA molecules, which do not migrate in the gels, are the precursors for the mature viral DNA. Centrifugation of deoxycholate-treated infected nuclei in sucrose gradients revealed that most of the viral DNA co-sedimented with the cellular DNA. The DNA-dependent RNA polymerase activity also co-sedimented with the viral and cellular DNA. Incubation of nuclei isolated from HSV-infected cells, under in vitro conditions that support DNA synthesis, resulted in the synthesis of viral molecules of low molecular weight. Under the same conditions, nuclei from Burkitt lymphoblasts did not synthesize DNA. The nature of the association between cellular DNA and EBV DNA was studied by hybridization with EBV cRNA. EBV-specific sequences were found in the lymphoblast DNA; they banded at a density of 1.707 g/cm3. Some of the viral mRNA transcribed in HSV-infected nuclei is symmetrically transcribed from HSV DNA. The symmetrical portions of the RNA are removed, since poly (A)-containing mRNA molecules lack homologous sequences. Most of the RNA synthesized in HSV-infected nuclei can be released after incubation of the nuclei in vitro in the presence of ATP. The released RNA consists of poly(A)plus and poly (A)-minus molecules. The mechanism of RNA transport from the nuclei still remains to be studied."}
{"id": "PMID:190128", "title": "Partial purification and biochemical characterization of herpesvirus saimiri.", "content": "HVS propagated in Vero cells was labelled with 3H-leucine and purified by isopycnic flotation in sucrose. Electron microscopic examination revealed both complete and incomplete HVS. No significant contamination  with cellular debris was noted. Polyacrylamide gel electrophoresis analysis of solubilized virus revealed at least 12 proteins varying in molecular weight from 8 000 to 200 000 daltons.", "contents": "Partial purification and biochemical characterization of herpesvirus saimiri. HVS propagated in Vero cells was labelled with 3H-leucine and purified by isopycnic flotation in sucrose. Electron microscopic examination revealed both complete and incomplete HVS. No significant contamination  with cellular debris was noted. Polyacrylamide gel electrophoresis analysis of solubilized virus revealed at least 12 proteins varying in molecular weight from 8 000 to 200 000 daltons."}
{"id": "PMID:190134", "title": "Immunological studies with hamster cells transformed by cytomegalovirus and herpes simplex virus type 1.", "content": "Evidence is presented that cells transformed by CMV and HSV-1 express virus-associated antigens on the cell surface. The finding that hyper-immune antivirus sera block cellular immunity in vitro may explain why virus-immunized hosts have thus far not been found to reject isografts of these cells.", "contents": "Immunological studies with hamster cells transformed by cytomegalovirus and herpes simplex virus type 1. Evidence is presented that cells transformed by CMV and HSV-1 express virus-associated antigens on the cell surface. The finding that hyper-immune antivirus sera block cellular immunity in vitro may explain why virus-immunized hosts have thus far not been found to reject isografts of these cells."}
{"id": "PMID:190145", "title": "Differences between laboratory strains of Epstein-Barr virus based on immortalization, abortive infection and interference.", "content": "Biological activities of extracellular Epstein-Barr virus (EBV) from two laboratory strains, namely P3J-HR-1 (P-H) from Burkitt's lymphoma and B95-8 (B95) from infectious mononucleosis, were compared. Virus stocks from both sources contained approximately the same number of virions. Virus from the P-H line induced early antigen in six non-producer EBV-genome carrier cell lines; virus from B95 did not induce early antigen. Extracellular virus from B95 regularly caused lymphocytes from human umbilical cords to form continuous lines (immortalization); P-H virus did not cause primary cultures of human lymphocytes to grow continuously. B95 virus stimulated DNA synthesis, as determined by the rate of incorporation of 3H-thymidine into acid-insoluble material; P-H virus did not stimulate DNA synthesis. Pretreatment of lymphocytes with undiluted P-H virus inhibited immortalization and stimulation of DNA  synthesis by B95 virus. The inhibitory properties of the P-H virus were sedimented at 100 000 g and inactivated by heat and UV irradiation; interference by the P-H virus was neutralized by human serum with antibody to EBV and not by antibody-negative human serum. The hypothesis most consistent with these results is that the P-H virus is defective in gene(s) needed for initiation of immortalization. We speculate that the absence of this gene allows early antigen to be expressed upon superinfection of non-producer cell lines. The availability of two laboratory strains of two laboratory strains of EBV that differ in biological behaviour provides starting material for analysis of the mechanism of lymphocyte immortalization by EBV and of virus structural differences that affect immortalization.", "contents": "Differences between laboratory strains of Epstein-Barr virus based on immortalization, abortive infection and interference. Biological activities of extracellular Epstein-Barr virus (EBV) from two laboratory strains, namely P3J-HR-1 (P-H) from Burkitt's lymphoma and B95-8 (B95) from infectious mononucleosis, were compared. Virus stocks from both sources contained approximately the same number of virions. Virus from the P-H line induced early antigen in six non-producer EBV-genome carrier cell lines; virus from B95 did not induce early antigen. Extracellular virus from B95 regularly caused lymphocytes from human umbilical cords to form continuous lines (immortalization); P-H virus did not cause primary cultures of human lymphocytes to grow continuously. B95 virus stimulated DNA synthesis, as determined by the rate of incorporation of 3H-thymidine into acid-insoluble material; P-H virus did not stimulate DNA synthesis. Pretreatment of lymphocytes with undiluted P-H virus inhibited immortalization and stimulation of DNA  synthesis by B95 virus. The inhibitory properties of the P-H virus were sedimented at 100 000 g and inactivated by heat and UV irradiation; interference by the P-H virus was neutralized by human serum with antibody to EBV and not by antibody-negative human serum. The hypothesis most consistent with these results is that the P-H virus is defective in gene(s) needed for initiation of immortalization. We speculate that the absence of this gene allows early antigen to be expressed upon superinfection of non-producer cell lines. The availability of two laboratory strains of two laboratory strains of EBV that differ in biological behaviour provides starting material for analysis of the mechanism of lymphocyte immortalization by EBV and of virus structural differences that affect immortalization."}
{"id": "PMID:190146", "title": "Appearance of Epstein-Barr virus nuclear antigen in human cordblood lymphocytes.", "content": "Transformation and induction of EBV-specified EBNA was studied in human umbilical cord-blood lymphocytes infected with EBV, HVS or HVA. Transformation of human umbilical umbilical cord-blood lymphocytes into continuous lymphoblastoid cell lines was successful with EBV derived from five of seven human or simian cell lines but not with HVS or HVA derived from simian lymphoblastoid cell lines. EBNA induction was studied using B95-8 virus for infection of lymphocytes; as early as 24 hours after infection, a few EBNA-positive cells were identified in 10 of 12 samples studied. Thereafter, the number of EBNA-positive cells increased progressively and by day 12, 50% of cells contained EBNA; after 18-20 days, approximately 85-90% of cells were EBNA-positive.", "contents": "Appearance of Epstein-Barr virus nuclear antigen in human cordblood lymphocytes. Transformation and induction of EBV-specified EBNA was studied in human umbilical cord-blood lymphocytes infected with EBV, HVS or HVA. Transformation of human umbilical umbilical cord-blood lymphocytes into continuous lymphoblastoid cell lines was successful with EBV derived from five of seven human or simian cell lines but not with HVS or HVA derived from simian lymphoblastoid cell lines. EBNA induction was studied using B95-8 virus for infection of lymphocytes; as early as 24 hours after infection, a few EBNA-positive cells were identified in 10 of 12 samples studied. Thereafter, the number of EBNA-positive cells increased progressively and by day 12, 50% of cells contained EBNA; after 18-20 days, approximately 85-90% of cells were EBNA-positive."}
{"id": "PMID:190147", "title": "Presence of a herpes simplex virus type 1 genome fragment in HSV-transformed cells.", "content": "LTK-cells infected with UV-irradiated HSV produce transformants that contain a thymidine kinase  (TK) activity not found in the parental LTK-line (Munyon et al., 1971). One of these (TK+) transformants (clone 139) has been analysed for the presence of the HSV genome. Reassociation kinetics studies with iodinated HSV DNA of specific activity of about 9 x 107 cpm/mug have established that there are approximately six copies of a fragment comprising about 15% of the HSV genome in HSV-transformed clone 139. Neither the parental LTK-nor a \"revertant\" cell line (clone 139 BUDR) obtained from clone 139 showed any detectable HSV-specific sequences. Analysis of data on RNA-125I-HSV DNA reassociation kinetics indicates that perhaps 5% of the HSV genome is transcribed in HSV-transformed clone 139. These results indicate that transformation is probably maintained by the presence of only a fraction of the HSV genome in the TK+ clones.", "contents": "Presence of a herpes simplex virus type 1 genome fragment in HSV-transformed cells. LTK-cells infected with UV-irradiated HSV produce transformants that contain a thymidine kinase  (TK) activity not found in the parental LTK-line (Munyon et al., 1971). One of these (TK+) transformants (clone 139) has been analysed for the presence of the HSV genome. Reassociation kinetics studies with iodinated HSV DNA of specific activity of about 9 x 107 cpm/mug have established that there are approximately six copies of a fragment comprising about 15% of the HSV genome in HSV-transformed clone 139. Neither the parental LTK-nor a \"revertant\" cell line (clone 139 BUDR) obtained from clone 139 showed any detectable HSV-specific sequences. Analysis of data on RNA-125I-HSV DNA reassociation kinetics indicates that perhaps 5% of the HSV genome is transcribed in HSV-transformed clone 139. These results indicate that transformation is probably maintained by the presence of only a fraction of the HSV genome in the TK+ clones."}
{"id": "PMID:190156", "title": "Some biological properties of herpesvirus saimiri from chronically infected monolayer and suspension cultures.", "content": "HVS-MEST cells, which are adherent, produced more infectious HVS at 37 degress C than at 33 degrees C. This was paralleled by the appearance of EA and LA in rounded cells and CF antigen in the cell cultures. In contrast, MLC-1 cells, which grow in suspension, produced hardly any infectious virus, but did produce more HVS S antigen than did the HVS-MEST cells. Production of S antigen in MLC-1 cells was augmented by treatment of the cells with BUDR. HVS-MEST cells could be superinfected with HVS, but MLC-1 cells were resistant to super-infection. The unpurified S antigens from both cell lines gave almost identical spectra when tested in CF against a battery of 10 owl and squirrel monkey sera. Thus, two cell lines have been described, one that produces infectious virus and S antigen, and another that produces more S antigen, but in the absence of any great amounts of infectious virus.", "contents": "Some biological properties of herpesvirus saimiri from chronically infected monolayer and suspension cultures. HVS-MEST cells, which are adherent, produced more infectious HVS at 37 degress C than at 33 degrees C. This was paralleled by the appearance of EA and LA in rounded cells and CF antigen in the cell cultures. In contrast, MLC-1 cells, which grow in suspension, produced hardly any infectious virus, but did produce more HVS S antigen than did the HVS-MEST cells. Production of S antigen in MLC-1 cells was augmented by treatment of the cells with BUDR. HVS-MEST cells could be superinfected with HVS, but MLC-1 cells were resistant to super-infection. The unpurified S antigens from both cell lines gave almost identical spectra when tested in CF against a battery of 10 owl and squirrel monkey sera. Thus, two cell lines have been described, one that produces infectious virus and S antigen, and another that produces more S antigen, but in the absence of any great amounts of infectious virus."}
{"id": "PMID:190163", "title": "Source, alterations, characteristics and use of a new dog cell line (Cf2Th).", "content": "A cell line derived from normal fetal canine thymus (Cf2Th) has been in culture since 1967. During cultivation the cells have changed morphologically from a fibroblast-like to flat, fusiform appearance and karyologically from diploid (2n=78) with 76 telocentric autosomes to hypodiploid with newly formed atelocentric chromosomes. The cells retain canine characteristic enzyme activity (G6PD and LDH) as well as cell membrane fluorescence and are free of mycoplasma. High passage cells produce tumors in ATST mice. No endogenous viruses have been detected in these cells. No original publication exists, to date, on the origin of this line, but seed stocks thereof have been distributed to many laboratories and the cells have served as experimental substrates in a number of published works on oncology albeit under different designations. The present information is offered in order to establish the provenance of this valuable cell line and to list characteristics which may serve to monitor for its purity and to distinguish it from other existing cell lines of dog origin also in common use.", "contents": "Source, alterations, characteristics and use of a new dog cell line (Cf2Th). A cell line derived from normal fetal canine thymus (Cf2Th) has been in culture since 1967. During cultivation the cells have changed morphologically from a fibroblast-like to flat, fusiform appearance and karyologically from diploid (2n=78) with 76 telocentric autosomes to hypodiploid with newly formed atelocentric chromosomes. The cells retain canine characteristic enzyme activity (G6PD and LDH) as well as cell membrane fluorescence and are free of mycoplasma. High passage cells produce tumors in ATST mice. No endogenous viruses have been detected in these cells. No original publication exists, to date, on the origin of this line, but seed stocks thereof have been distributed to many laboratories and the cells have served as experimental substrates in a number of published works on oncology albeit under different designations. The present information is offered in order to establish the provenance of this valuable cell line and to list characteristics which may serve to monitor for its purity and to distinguish it from other existing cell lines of dog origin also in common use."}
{"id": "PMID:190164", "title": "Persistent infection with bovine herpesvirus-1 (infectious bovine rhinotracheitis virus) in cultured hamster cells.", "content": "Bovine herpesvirus-1 infection in hamster embryo cells was found to be dependent upon input multiplicity; productive infection was achieved at input multiplicities greater than one, while persistent infection was established when input multiplicities were about 0.5. This persistence was characterized by a noncyclic, minimal degree of cytopathic effect with a low level of released virus. Maintenance of the persistently infected cultures did not require external supportive measures. Subcultivation of the persistently infected cultures led to virus replication followed by CPE and then cell regrowth. With 3 to 4 weeks after subcultivation a persistent infection was re-established. The possible mechanism for the bovine herpesvirus persistence in hamster cells is discussed.", "contents": "Persistent infection with bovine herpesvirus-1 (infectious bovine rhinotracheitis virus) in cultured hamster cells. Bovine herpesvirus-1 infection in hamster embryo cells was found to be dependent upon input multiplicity; productive infection was achieved at input multiplicities greater than one, while persistent infection was established when input multiplicities were about 0.5. This persistence was characterized by a noncyclic, minimal degree of cytopathic effect with a low level of released virus. Maintenance of the persistently infected cultures did not require external supportive measures. Subcultivation of the persistently infected cultures led to virus replication followed by CPE and then cell regrowth. With 3 to 4 weeks after subcultivation a persistent infection was re-established. The possible mechanism for the bovine herpesvirus persistence in hamster cells is discussed."}
{"id": "PMID:190165", "title": "[Comparison of value of four immunological methods (AST, ADNase B, AHy, ANADase) by A-streptococcal infections and their significance in the routine diagnostic (author's transl)].", "content": "In the sera of approximately 600 patients of all age groups, who were on clinical suspicion of an A-streptococcal infection, AST, ADNase B, AHy and ANADase were determined. The ANADase alone detects 90% of the acute A-streptococcal infections, the AHy and the ADNase B 80% and the ASO 50%. In skin infections superinfected by A-streptococci, the AHy is positive in 85%, the ANADase in 80%, the ADNase B in 75% and the AST in 40% of the cases. The most frequent A-streptococcal infection, Angina tonsillaris, is determined in the best manner possible through the combination ADNase B + ANADase + AHy. According to the statistical evaluation, the ADNase B and the ANADase are the most reliable tests. The age group of the 4 to 15 year-olds reaches for ASO, ADNase B and AHy a percentage of highly increased titers twice as high in comparison with the adult group. In no case does one test determine 100% of the collective; therefore, a combination of several antibody reactions is desirable for the diagnosis. Increased titers should be checked every four weeks, also normal titers with patients, who continue on the clinical suspicion of having an A-streptococcal infection, because their blood sample may have been taken before the immune reaction occurred.", "contents": "[Comparison of value of four immunological methods (AST, ADNase B, AHy, ANADase) by A-streptococcal infections and their significance in the routine diagnostic (author's transl)]. In the sera of approximately 600 patients of all age groups, who were on clinical suspicion of an A-streptococcal infection, AST, ADNase B, AHy and ANADase were determined. The ANADase alone detects 90% of the acute A-streptococcal infections, the AHy and the ADNase B 80% and the ASO 50%. In skin infections superinfected by A-streptococci, the AHy is positive in 85%, the ANADase in 80%, the ADNase B in 75% and the AST in 40% of the cases. The most frequent A-streptococcal infection, Angina tonsillaris, is determined in the best manner possible through the combination ADNase B + ANADase + AHy. According to the statistical evaluation, the ADNase B and the ANADase are the most reliable tests. The age group of the 4 to 15 year-olds reaches for ASO, ADNase B and AHy a percentage of highly increased titers twice as high in comparison with the adult group. In no case does one test determine 100% of the collective; therefore, a combination of several antibody reactions is desirable for the diagnosis. Increased titers should be checked every four weeks, also normal titers with patients, who continue on the clinical suspicion of having an A-streptococcal infection, because their blood sample may have been taken before the immune reaction occurred."}
{"id": "PMID:190170", "title": "Effects of in vivo administered B. pertussis and other adjuvants on the mitotic responses of lymphocytes in vitro.", "content": "Intraperitoneal treatment of mice with adjuvants affects the in vitro response of their lymphocytes toward class-specific mitogen. Spleen cells from animals injected with Corynebacterium parvum organisms showed in some cases an increase in their response to all mitogens, while in other experiments, a moderate decrease in the reaction to T-specific mitogens (concanavalin A and phytohemagglutinin) was found. Injection of lipopolysaccharide (LPS) and in particular Bordetella pertussis bacteria, brought about a marked reduction in the response of spleen cells to B mitogens (LPS and PPD) but had little or no effect on the reaction to the T mitogens. Intraperitoneal administration of B. pertussis caused a marked depletion of lymph nodes and a high level of lymphocytosis. Blood cells of the treated mice showed an increased response to T mitogens, whereas mesenterial lymph node cultures reacted higher than the controls to LPS and without stimulation. No change was noted in the responses of cells from the axillary lymph nodes of these pertussis-treated mice.", "contents": "Effects of in vivo administered B. pertussis and other adjuvants on the mitotic responses of lymphocytes in vitro. Intraperitoneal treatment of mice with adjuvants affects the in vitro response of their lymphocytes toward class-specific mitogen. Spleen cells from animals injected with Corynebacterium parvum organisms showed in some cases an increase in their response to all mitogens, while in other experiments, a moderate decrease in the reaction to T-specific mitogens (concanavalin A and phytohemagglutinin) was found. Injection of lipopolysaccharide (LPS) and in particular Bordetella pertussis bacteria, brought about a marked reduction in the response of spleen cells to B mitogens (LPS and PPD) but had little or no effect on the reaction to the T mitogens. Intraperitoneal administration of B. pertussis caused a marked depletion of lymph nodes and a high level of lymphocytosis. Blood cells of the treated mice showed an increased response to T mitogens, whereas mesenterial lymph node cultures reacted higher than the controls to LPS and without stimulation. No change was noted in the responses of cells from the axillary lymph nodes of these pertussis-treated mice."}
{"id": "PMID:190171", "title": "Role of cyclic nucleotides in human lymphocyte-mediated antibody-dependent cytotoxicity.", "content": "Experiments were carried out in order to throw light on the role of cyclic AMP and cyclic GMP in the modulation of the expression of antibody-dependent cytotoxicity mediated by human peripheral blood lymphocytes in vitro. Chicken erythrocytes were used as target cells. Support for an inhibitory role of cyclic AMP was derived from the marked suppression of cytotoxicity by dibutyryl cyclic AMP. Cyclic AMP itself had little effect. Isoproterenol, prostaglandin E1 and prostaglandin E2 increased cyclic AMP concentrations and strongly inhibited the cytotoxic effect of the lymphocytes. Histamine showed very slight elevation of the cyclic AMP level and suppression of the cytotoxicity. Theophylline did not increase the cyclic AMP concentration, but potentiated the effects of isoproterenol and prostaglandin E1 on the cyclic AMP levels, and significantly inhibited cytotoxicity. No clear effects were seen when cyclic GMP, dibutyryl GMP, acetylcholine or carbacholine were added to the cells. The results indicate that in this system cyclic AMP inhibits cytotoxicity, while no evidence for a role of cyclic GMP has been obtained.", "contents": "Role of cyclic nucleotides in human lymphocyte-mediated antibody-dependent cytotoxicity. Experiments were carried out in order to throw light on the role of cyclic AMP and cyclic GMP in the modulation of the expression of antibody-dependent cytotoxicity mediated by human peripheral blood lymphocytes in vitro. Chicken erythrocytes were used as target cells. Support for an inhibitory role of cyclic AMP was derived from the marked suppression of cytotoxicity by dibutyryl cyclic AMP. Cyclic AMP itself had little effect. Isoproterenol, prostaglandin E1 and prostaglandin E2 increased cyclic AMP concentrations and strongly inhibited the cytotoxic effect of the lymphocytes. Histamine showed very slight elevation of the cyclic AMP level and suppression of the cytotoxicity. Theophylline did not increase the cyclic AMP concentration, but potentiated the effects of isoproterenol and prostaglandin E1 on the cyclic AMP levels, and significantly inhibited cytotoxicity. No clear effects were seen when cyclic GMP, dibutyryl GMP, acetylcholine or carbacholine were added to the cells. The results indicate that in this system cyclic AMP inhibits cytotoxicity, while no evidence for a role of cyclic GMP has been obtained."}
{"id": "PMID:190173", "title": "Detection of Epstein-Barr virus early antigen-D and its antibodies by passive hemagglutination.", "content": "These data describe the use of a passive hemagglutination test (PHAT) for the detection of antibodies to the Epstein-Barr virus (EBV) associated antigen, early antigen-D (EA-D). EA-D was obtained from EBV-superinfected RPMI 64-10 cell preparations which showed by immunofluorescent staining (IF) that 25-35% of the cells contained EA-D. Solubilization of EA-D was achieved by sonic oscillation, treatment of the pellet-associated material with triton X 100, ammonium sulfate precipitation, and chromatography on diethylaminoethyl celluiose. Successful use of the PHAT for detection of antibodies to EA-D was dependent on the degree of purity of the partially purified antigen. Throughout these studies preparations from uninfected 64-10 cells were used as control reagents. More than 100 human antisera from patients with EBV-associated diseases, which had been previously tested by standard IF procedures were assayed by PHAT. A good correlation was found between IF and PHAT titers for EA-D and, in addition, the PHAT was 50-100 times more sensitive. Most human sera gave no agglutination of red cells coated with control preparations. An inhibition (blocking) of PHAT was developed which was useful in the purification and characterization of EA-D. These data indicate that the PHAT may provide a rapid, reliable, objective and sensitive method for studying EA-D and possibly other virus-associated antigens.", "contents": "Detection of Epstein-Barr virus early antigen-D and its antibodies by passive hemagglutination. These data describe the use of a passive hemagglutination test (PHAT) for the detection of antibodies to the Epstein-Barr virus (EBV) associated antigen, early antigen-D (EA-D). EA-D was obtained from EBV-superinfected RPMI 64-10 cell preparations which showed by immunofluorescent staining (IF) that 25-35% of the cells contained EA-D. Solubilization of EA-D was achieved by sonic oscillation, treatment of the pellet-associated material with triton X 100, ammonium sulfate precipitation, and chromatography on diethylaminoethyl celluiose. Successful use of the PHAT for detection of antibodies to EA-D was dependent on the degree of purity of the partially purified antigen. Throughout these studies preparations from uninfected 64-10 cells were used as control reagents. More than 100 human antisera from patients with EBV-associated diseases, which had been previously tested by standard IF procedures were assayed by PHAT. A good correlation was found between IF and PHAT titers for EA-D and, in addition, the PHAT was 50-100 times more sensitive. Most human sera gave no agglutination of red cells coated with control preparations. An inhibition (blocking) of PHAT was developed which was useful in the purification and characterization of EA-D. These data indicate that the PHAT may provide a rapid, reliable, objective and sensitive method for studying EA-D and possibly other virus-associated antigens."}
{"id": "PMID:190174", "title": "Herpesvirus infection and cervical anaplasia: a seroepidemiological study.", "content": "In a cohort of 23,146 pregnant females followed for 37-56 months subsequent to collection of prenatal sera, 57 cases of carcinoma of the cervix were encountered. Three controls were selected for each case from the residual cohort matched to cases for age, residence, number of prior cytology smears taken, and the data of entry to the study. The antibody activity to herpesvirus type 1 and type 2 was examined by the indirect hemagglutination test. The proportion of cases positive for HSV-2 infection was greater than that of the controls; however, the difference was not significant at the 5% level. The relative risk value for the association between HSV-2 infection and carcinoma of the cervix was found to be 2.33. The geometric mean titers of IHAT revealed that the cases of cervical cancer had a higher titer than the controls with respect to HSV-1 as well as HSV-2 antibodies. A sufficiently longer follow-up, yielding a larger sample size, is desired to assess the specific role of HSV-2 infection in development of cervical anaplasia.", "contents": "Herpesvirus infection and cervical anaplasia: a seroepidemiological study. In a cohort of 23,146 pregnant females followed for 37-56 months subsequent to collection of prenatal sera, 57 cases of carcinoma of the cervix were encountered. Three controls were selected for each case from the residual cohort matched to cases for age, residence, number of prior cytology smears taken, and the data of entry to the study. The antibody activity to herpesvirus type 1 and type 2 was examined by the indirect hemagglutination test. The proportion of cases positive for HSV-2 infection was greater than that of the controls; however, the difference was not significant at the 5% level. The relative risk value for the association between HSV-2 infection and carcinoma of the cervix was found to be 2.33. The geometric mean titers of IHAT revealed that the cases of cervical cancer had a higher titer than the controls with respect to HSV-1 as well as HSV-2 antibodies. A sufficiently longer follow-up, yielding a larger sample size, is desired to assess the specific role of HSV-2 infection in development of cervical anaplasia."}
{"id": "PMID:190175", "title": "Polyoma genome transcription in transformed mouse cells growing in culture and as tumors in syngeneic mice.", "content": "The strands of the polyoma genome coding for early and late viral RNA were separated by means of asymmetric cRNA synthesized under high salt conditions by Escherichia coli RNA polymerase. Each strand was then employed in RNA-DNA hybridization experiments to determine the degree to which it is transcribed in transformed cells under several conditions. Except for a concanavalin-A-selected revertant, approximately one-quarter of the early strand was expressed in all of the situations investigated. In contrast, while no significant late strand transcription was detected in transformed cells in culture, the tumors induced by these cells contained transcripts complementary to about 12% of this strand. The results are discussed in terms of current knowledge of the amount of the virus genome required to transform cells.", "contents": "Polyoma genome transcription in transformed mouse cells growing in culture and as tumors in syngeneic mice. The strands of the polyoma genome coding for early and late viral RNA were separated by means of asymmetric cRNA synthesized under high salt conditions by Escherichia coli RNA polymerase. Each strand was then employed in RNA-DNA hybridization experiments to determine the degree to which it is transcribed in transformed cells under several conditions. Except for a concanavalin-A-selected revertant, approximately one-quarter of the early strand was expressed in all of the situations investigated. In contrast, while no significant late strand transcription was detected in transformed cells in culture, the tumors induced by these cells contained transcripts complementary to about 12% of this strand. The results are discussed in terms of current knowledge of the amount of the virus genome required to transform cells."}
{"id": "PMID:190176", "title": "Effects of ethylnitrosourea administration during pregnancy on three subsequent generations of BDVI Rats.", "content": "A single dose of 40 mg/kg of N-nitrosoethylurea (ENU) was administered to BDVI rats on the 16th day of pregnancy. The first generation descendants (F1) were mated on a brother-to-sister system to produce a second generation (F2) which was then mated to produce a third generation. A high incidence of nervous tissue tumors and a few kidney tumours were observed in F1 descendants. A few nervous tissue tumours were observed in F3 but not in F2 descendants. These results partially confirm previous observations obtained with 7,12-dimethylbenz(a)anthracene in mice and nitrosomethylurea in rats and indicate that prenatal exposure to a chemical carcinogen may result in an increased cancer risk which can persist for more than one generation.", "contents": "Effects of ethylnitrosourea administration during pregnancy on three subsequent generations of BDVI Rats. A single dose of 40 mg/kg of N-nitrosoethylurea (ENU) was administered to BDVI rats on the 16th day of pregnancy. The first generation descendants (F1) were mated on a brother-to-sister system to produce a second generation (F2) which was then mated to produce a third generation. A high incidence of nervous tissue tumors and a few kidney tumours were observed in F1 descendants. A few nervous tissue tumours were observed in F3 but not in F2 descendants. These results partially confirm previous observations obtained with 7,12-dimethylbenz(a)anthracene in mice and nitrosomethylurea in rats and indicate that prenatal exposure to a chemical carcinogen may result in an increased cancer risk which can persist for more than one generation."}
{"id": "PMID:190177", "title": "Detergent solubilization and partial purification of tumor specific surface and transplantation antigens from SV40-virus-transformed mouse cells.", "content": "A solubilization technique employing 0.5% Triton X-100 was developed to obtain both SV40 virus (SV40)-induced tumor-specific surface antigen(s) (TSSA) from SV40-transformed mouse cells, as determined by a serum-mediated microcytolytic assay, and tumor-specific transplantation antigen(s) (TSTA), as determined by in invivo experiments. High yields (approximately 50%) of TSSA were obtained in whole-cell extracts and also after ammonium sulfate fractionation. Additional fractionation of a 30-50% ammonium sulfate fraction by gel exclusion chromatography on Sephadex G-150 resulted in two pooled fractions which contained TSSA activity. The first eluted close to the void volume, and the second in the 45,000 molecular weight region. The various TSSA active fractions were also active in vivo TSTA tests. Detergent solubilization provides a suitable technique to recover the SV40-induced antigens in good yield, and apparently in intact form.", "contents": "Detergent solubilization and partial purification of tumor specific surface and transplantation antigens from SV40-virus-transformed mouse cells. A solubilization technique employing 0.5% Triton X-100 was developed to obtain both SV40 virus (SV40)-induced tumor-specific surface antigen(s) (TSSA) from SV40-transformed mouse cells, as determined by a serum-mediated microcytolytic assay, and tumor-specific transplantation antigen(s) (TSTA), as determined by in invivo experiments. High yields (approximately 50%) of TSSA were obtained in whole-cell extracts and also after ammonium sulfate fractionation. Additional fractionation of a 30-50% ammonium sulfate fraction by gel exclusion chromatography on Sephadex G-150 resulted in two pooled fractions which contained TSSA activity. The first eluted close to the void volume, and the second in the 45,000 molecular weight region. The various TSSA active fractions were also active in vivo TSTA tests. Detergent solubilization provides a suitable technique to recover the SV40-induced antigens in good yield, and apparently in intact form."}
{"id": "PMID:190178", "title": "Follow-up of a token economy applied to civilly committed narcotic addicts.", "content": "Thirty-one civil-commitment, male, heroin addicts participated in an intramural token economy designed to reinforce the rehabilitative process by programming the incentive of length of residential stay. The project evaluated participation in rehabilitative activities during intramural stay, personality change as measured by the MMPI, and follow-up of the participants' community aftercare retention. The token economy had a substantial impact on the participants' institutional adjustment but had little influence on the evaluative dimensions of personality change and rate of aftercare retention.", "contents": "Follow-up of a token economy applied to civilly committed narcotic addicts. Thirty-one civil-commitment, male, heroin addicts participated in an intramural token economy designed to reinforce the rehabilitative process by programming the incentive of length of residential stay. The project evaluated participation in rehabilitative activities during intramural stay, personality change as measured by the MMPI, and follow-up of the participants' community aftercare retention. The token economy had a substantial impact on the participants' institutional adjustment but had little influence on the evaluative dimensions of personality change and rate of aftercare retention."}
{"id": "PMID:190179", "title": "Effects of gaba, gabob and some anticonvulsant drugs on dibutyryl cyclic AMP evoked seizures.", "content": "The present experiments were undertaken to study the possible effects of Gaba, Gabob, phenobarbitone, diphenylhydantoin, and diazepam given systemically on convulsant activity evoked in chicks by intrahypothalamic injection of dibutyryl cyclic AMP (cAMP). Diphenylhydantoin and phenobarbitone antagonized the effect of dibutyryl cAMP but unfortunately the effects of Gaba and Gabob were complicated by osmotic effects. Diazepam, an anticonvulsant benzodiazepine, did not affect dibutyryl cAMP-induced electrocortical spiking. The dibutyryl cAMP-induced syndrome seems to be of limited value as a model for assessing the activity of anticonvulsant drugs are present.", "contents": "Effects of gaba, gabob and some anticonvulsant drugs on dibutyryl cyclic AMP evoked seizures. The present experiments were undertaken to study the possible effects of Gaba, Gabob, phenobarbitone, diphenylhydantoin, and diazepam given systemically on convulsant activity evoked in chicks by intrahypothalamic injection of dibutyryl cyclic AMP (cAMP). Diphenylhydantoin and phenobarbitone antagonized the effect of dibutyryl cAMP but unfortunately the effects of Gaba and Gabob were complicated by osmotic effects. Diazepam, an anticonvulsant benzodiazepine, did not affect dibutyryl cAMP-induced electrocortical spiking. The dibutyryl cAMP-induced syndrome seems to be of limited value as a model for assessing the activity of anticonvulsant drugs are present."}
{"id": "PMID:190180", "title": "Purification of protected syntheic peptides by preparative high performance liquid chromatography on silica gel 60.", "content": "A simple preparative system is described for rapid and efficient purification of protected synthetic peptides on a gram scale by high performance liquid chromatography on prepacked silica gel 60 columns. A variety of protected peptides up to tetradecapeptides have been chromatographed at pressures of 50 to 150 psi and obtained in analytically pure from within 2 to 4 h. With such commonly used protecting groups as N-benzyloxycarbonyl (Z), N-2-(p-biphenylyl)-2-propyloxycarbonyl (Bpoc), N-t-butyloxycarbonyl (Boc), O- and S-t-butyl (But), and S-acetamidomethyl (Acm), compounds were sufficiently soluble in chloroform, alcohols, acetic acid, or mixtures of these solvents for column loading. Dimethylformamide was also used as a solvent for loading. Solvent systems for column elution in isocratic, stepwise, or gradient modes were composed of chloroform, isopropanol, ethanol, or methanol and acetic acid in ratios that differed for each protected peptide depending on Rf values on t.l.c. plates. A simple chromatography is described which was self-assembled using standard instruments commonly in use in most laboratories. A shut-off valve was designed to prevent loss of material between fractions.", "contents": "Purification of protected syntheic peptides by preparative high performance liquid chromatography on silica gel 60. A simple preparative system is described for rapid and efficient purification of protected synthetic peptides on a gram scale by high performance liquid chromatography on prepacked silica gel 60 columns. A variety of protected peptides up to tetradecapeptides have been chromatographed at pressures of 50 to 150 psi and obtained in analytically pure from within 2 to 4 h. With such commonly used protecting groups as N-benzyloxycarbonyl (Z), N-2-(p-biphenylyl)-2-propyloxycarbonyl (Bpoc), N-t-butyloxycarbonyl (Boc), O- and S-t-butyl (But), and S-acetamidomethyl (Acm), compounds were sufficiently soluble in chloroform, alcohols, acetic acid, or mixtures of these solvents for column loading. Dimethylformamide was also used as a solvent for loading. Solvent systems for column elution in isocratic, stepwise, or gradient modes were composed of chloroform, isopropanol, ethanol, or methanol and acetic acid in ratios that differed for each protected peptide depending on Rf values on t.l.c. plates. A simple chromatography is described which was self-assembled using standard instruments commonly in use in most laboratories. A shut-off valve was designed to prevent loss of material between fractions."}
{"id": "PMID:190186", "title": "Synthesis and transport of herpes simplex virus proteins in arginine-deprived BSC-1 cells.", "content": "The synthesis and transport of [35S]methionine-labeled peptides from the cytoplasm to the nucleus of herpes simplex virus-infected cells was studied by polyacrylamide gel electrophoresis, using autoradiography of the labeled peptides, In complete medium the transport of proteins from the cytoplasm to the nucleus is a selective process and different peptides are transported at different rates. In arginine-deficient medium, the synthesis of viral peptides in the cytoplasm is reduced and the labeled proteins are transported slowly to the nucleus. These viral peptides gradually disappear from the cytoplasm, suggesting degradation of the synthesized proteins.", "contents": "Synthesis and transport of herpes simplex virus proteins in arginine-deprived BSC-1 cells. The synthesis and transport of [35S]methionine-labeled peptides from the cytoplasm to the nucleus of herpes simplex virus-infected cells was studied by polyacrylamide gel electrophoresis, using autoradiography of the labeled peptides, In complete medium the transport of proteins from the cytoplasm to the nucleus is a selective process and different peptides are transported at different rates. In arginine-deficient medium, the synthesis of viral peptides in the cytoplasm is reduced and the labeled proteins are transported slowly to the nucleus. These viral peptides gradually disappear from the cytoplasm, suggesting degradation of the synthesized proteins."}
{"id": "PMID:190190", "title": "[Report of a case of Goltz-Gorlin syndrome].", "content": "A case of Goltz-Gorlin-syndrome (congenital ectodermal and mesodermal dysplasia) in a 8 1/2 year old girl with focal dermal aplasia after birth, poikilodermia, anomalies of nails, hair, teeth, eyes and bones is presented.", "contents": "[Report of a case of Goltz-Gorlin syndrome]. A case of Goltz-Gorlin-syndrome (congenital ectodermal and mesodermal dysplasia) in a 8 1/2 year old girl with focal dermal aplasia after birth, poikilodermia, anomalies of nails, hair, teeth, eyes and bones is presented."}
{"id": "PMID:190193", "title": "Cytophotometry of post mortem glycogenolysis in different histochemical types of muscle fibres of the pig.", "content": "Serial transverse sections of porcine longissimus dorsi muscle (18 pigs, 50 to 178 kg live weight) were reacted for NAD tetrazolium reductase and ATPase at pH 9.4, and for glycogen with the periodic acid-Schiff (PAS) reaction. Three histochemical types of muscle fibre were identified; (1) strong ATPase and weak NADH oxidative activity; (2) strong ATPase and intermediate NADH oxidative activity; and (3) weak ATPase and strong NADH oxidative activity. Immediate post mortem samples from one side of each animal were compared with a later post mortem sample from the other side by measuring the absorbance of PAS-stained glycogen at 570 nm with a microscope photometer. Later post mortem absorbance was expressed as a percentage of immediate post mortem absorbance in each category of muscle fibre in order to compensate for distributional error and different starting levels of glycogen. Muscle fibres with weak ATPase and strong NADH oxidative activity showed a progressive decrease in absorbance of PAS-stained glycogen post mortem. In some animals, fibres with strong ATPase and intermediate or weak NADH oxidative activity showed an initial post mortem increase in absorbance of PAS-stained glycogen which was then followed by a progressive decrease. The maximum rates of decrease in absorbance in the three fibre types did not differ to any great extent.", "contents": "Cytophotometry of post mortem glycogenolysis in different histochemical types of muscle fibres of the pig. Serial transverse sections of porcine longissimus dorsi muscle (18 pigs, 50 to 178 kg live weight) were reacted for NAD tetrazolium reductase and ATPase at pH 9.4, and for glycogen with the periodic acid-Schiff (PAS) reaction. Three histochemical types of muscle fibre were identified; (1) strong ATPase and weak NADH oxidative activity; (2) strong ATPase and intermediate NADH oxidative activity; and (3) weak ATPase and strong NADH oxidative activity. Immediate post mortem samples from one side of each animal were compared with a later post mortem sample from the other side by measuring the absorbance of PAS-stained glycogen at 570 nm with a microscope photometer. Later post mortem absorbance was expressed as a percentage of immediate post mortem absorbance in each category of muscle fibre in order to compensate for distributional error and different starting levels of glycogen. Muscle fibres with weak ATPase and strong NADH oxidative activity showed a progressive decrease in absorbance of PAS-stained glycogen post mortem. In some animals, fibres with strong ATPase and intermediate or weak NADH oxidative activity showed an initial post mortem increase in absorbance of PAS-stained glycogen which was then followed by a progressive decrease. The maximum rates of decrease in absorbance in the three fibre types did not differ to any great extent."}
{"id": "PMID:190194", "title": "[Applied phoniatry. IV. Rhinophony (author's transl)].", "content": "Rhinophony, which is a change of vocal sound, can appear as a major symptom in many peripheral or central disorders of childhood, adolescence and adulthood. Its investigation, aetiology and management from various points of view are discussed. These are considered broadly as rhinophony aperta (palatal paralysis, functional rhinophony aperta, congenitally short palate); as rhinophony clausa (organic in origin, functional nasal speech); and mixed types of rhinophony. Typical phoniatric problems related to cleft lip and palate are also presented.", "contents": "[Applied phoniatry. IV. Rhinophony (author's transl)]. Rhinophony, which is a change of vocal sound, can appear as a major symptom in many peripheral or central disorders of childhood, adolescence and adulthood. Its investigation, aetiology and management from various points of view are discussed. These are considered broadly as rhinophony aperta (palatal paralysis, functional rhinophony aperta, congenitally short palate); as rhinophony clausa (organic in origin, functional nasal speech); and mixed types of rhinophony. Typical phoniatric problems related to cleft lip and palate are also presented."}
{"id": "PMID:190195", "title": "Fatal generalized feline viral rhinotracheitis in a young adult cat.", "content": "A 7-month-old cat died following a 17-day illness. Necropsy findings included sharply demarcated lingual ulcers and multifocal necrotic hepatitis. Intranuclear inclusions were found in the lesions, and a herpesvirus was recovered from specimens of liver and tongue. The virus was identified by neutralization with specific antiserum as feline rhinotracheitis virus.", "contents": "Fatal generalized feline viral rhinotracheitis in a young adult cat. A 7-month-old cat died following a 17-day illness. Necropsy findings included sharply demarcated lingual ulcers and multifocal necrotic hepatitis. Intranuclear inclusions were found in the lesions, and a herpesvirus was recovered from specimens of liver and tongue. The virus was identified by neutralization with specific antiserum as feline rhinotracheitis virus."}
{"id": "PMID:190196", "title": "A comparison of age estimation using discriminant function analysis with some other age estimations of unknown skulls.", "content": "Available methods of estimating the ages of unknown skulls are notoriously inaccurate. Making use of a unique opportunity to view several hundreds of remains from two nineteenth century cemeteries, various methods of estimating age were tested. A statistical method which gives relative weighting to each age indicator before reducing the data to a single pooled age estimate was found to be the most reliable. The greater the number of criteria which were utilized for age estimation, the more highly correlated was the estimated age of remains with the actual age at death. The degree of accuracy in estimating the ages of skulls of under 20 years was relatively high, when only the stage of development of dental tissues was examined. With increasing age over 20 the accuracy decreased, particularly at ages over 45. The range of age distribution of skulls estimated from published data on suture closure tended to be more restricted than that which may acutally occur.", "contents": "A comparison of age estimation using discriminant function analysis with some other age estimations of unknown skulls. Available methods of estimating the ages of unknown skulls are notoriously inaccurate. Making use of a unique opportunity to view several hundreds of remains from two nineteenth century cemeteries, various methods of estimating age were tested. A statistical method which gives relative weighting to each age indicator before reducing the data to a single pooled age estimate was found to be the most reliable. The greater the number of criteria which were utilized for age estimation, the more highly correlated was the estimated age of remains with the actual age at death. The degree of accuracy in estimating the ages of skulls of under 20 years was relatively high, when only the stage of development of dental tissues was examined. With increasing age over 20 the accuracy decreased, particularly at ages over 45. The range of age distribution of skulls estimated from published data on suture closure tended to be more restricted than that which may acutally occur."}
{"id": "PMID:190197", "title": "Regeneration of parietal and visceral peritoneum: an enzyme histochemical study.", "content": "The healing of parietal and visceral peritoneum has been studied by the techniques of enzyme histochemistry in an attempt to define more precisely the type of cell responsibile for forming the new mesothelium. The changes occurring in the distribution of the following enzymes throughout the course of healing have been investigated: acid phosphatase, alkaline phosphatase, ATPase and non-specific esterase. Regenerating mesothelial cells have been found to have several enzyme histochemical properties in common with subperitoneal connective tissue cells. It has not been possible to distinguish between primitive mesenchymal cells and subperitoneal fibroblasts by the histochemical techniques used in this study and therefore the study has not been fruitful in determining whether the new mesothelium arises from primitive mesenchymal cells or subperitoneal fibroblasts. The present study does, however, lend weight to the view that the new mesothelium is not derived from peritoneal macrophages.", "contents": "Regeneration of parietal and visceral peritoneum: an enzyme histochemical study. The healing of parietal and visceral peritoneum has been studied by the techniques of enzyme histochemistry in an attempt to define more precisely the type of cell responsibile for forming the new mesothelium. The changes occurring in the distribution of the following enzymes throughout the course of healing have been investigated: acid phosphatase, alkaline phosphatase, ATPase and non-specific esterase. Regenerating mesothelial cells have been found to have several enzyme histochemical properties in common with subperitoneal connective tissue cells. It has not been possible to distinguish between primitive mesenchymal cells and subperitoneal fibroblasts by the histochemical techniques used in this study and therefore the study has not been fruitful in determining whether the new mesothelium arises from primitive mesenchymal cells or subperitoneal fibroblasts. The present study does, however, lend weight to the view that the new mesothelium is not derived from peritoneal macrophages."}
{"id": "PMID:190198", "title": "The distribution and relative sizes of three histochemical fibre types in the rat tibialis anterior muscle.", "content": "A quantitative study of the tibialis anterior muscle of the adult rat showed that the proportions of each 'histochemical' fibre type varied between adjacent regions along the deep to superficial and medial to lateral axes of the muscle. The distribution of fibre types classified with oxidative enzymes was similar to that using phosphorylase, but differed from that obtained with sections stained for myosin ATPase. This apparent discrepancy in classifation was confirmed by comparison of the ranges of fibre cross sectional areas for each fibre type classified on the basis of their oxidative enzme and ATPase activites, and by an independent analysis of individual fibres in serial sections stained for succinic dehydrogenase and ATPase.", "contents": "The distribution and relative sizes of three histochemical fibre types in the rat tibialis anterior muscle. A quantitative study of the tibialis anterior muscle of the adult rat showed that the proportions of each 'histochemical' fibre type varied between adjacent regions along the deep to superficial and medial to lateral axes of the muscle. The distribution of fibre types classified with oxidative enzymes was similar to that using phosphorylase, but differed from that obtained with sections stained for myosin ATPase. This apparent discrepancy in classifation was confirmed by comparison of the ranges of fibre cross sectional areas for each fibre type classified on the basis of their oxidative enzme and ATPase activites, and by an independent analysis of individual fibres in serial sections stained for succinic dehydrogenase and ATPase."}
{"id": "PMID:190199", "title": "The postnatal development of the alimentary canal in the opossum. III. Small intestine and colon.", "content": "The duodenum of the newborn opossum exhibits a patent lumen containing scattered elongate villi, whereas the distal segments of the small intestine are smaller in diameter and are filled with short immature villi. The muscularis externa through the small intestine consists of a single layer of myoblasts. Interposed between the intestinal lining epithelium and the muscularis externa is an extensive capillary bed that occupies a considerable proportion of the intestinal wall. Additional villi appear to form during the postnatal period as a result of evaginations of the epithelium, together with underlying connective tissue and vasculature, into the intestinal lumen. Intestinal glands are not observed until 8.5cm, and are shallow in depth even in the adult. The epithelium of the entire small intestine is modified for absorption until just prior to weaning. The principal intestinal lining cells show an extensive apical endocytic complex, large supranuclear vacuoles and numerous cytoplasmic inclusions. Intestinal epithelial cells of the colon also appear to be modified for absorption during the first two weeks after birth. Although goblet cells and Paneth cells are present during the suckling period, they do not comprise a significant population in the intestinal epithelium until after weaning. In contrast to the small intestine, goblet cells are numerous in the colon by the ninth postnatal day. The significance of macromolecular absorption and the possibility of passive immunity being transmitted in the opossum during suckling are discussed and related to similar events that occur in the slckling young of several eutherian species. The possible functional significance of two large membranes that develop in the lamina propria of the intestines after weaning also is discussed.", "contents": "The postnatal development of the alimentary canal in the opossum. III. Small intestine and colon. The duodenum of the newborn opossum exhibits a patent lumen containing scattered elongate villi, whereas the distal segments of the small intestine are smaller in diameter and are filled with short immature villi. The muscularis externa through the small intestine consists of a single layer of myoblasts. Interposed between the intestinal lining epithelium and the muscularis externa is an extensive capillary bed that occupies a considerable proportion of the intestinal wall. Additional villi appear to form during the postnatal period as a result of evaginations of the epithelium, together with underlying connective tissue and vasculature, into the intestinal lumen. Intestinal glands are not observed until 8.5cm, and are shallow in depth even in the adult. The epithelium of the entire small intestine is modified for absorption until just prior to weaning. The principal intestinal lining cells show an extensive apical endocytic complex, large supranuclear vacuoles and numerous cytoplasmic inclusions. Intestinal epithelial cells of the colon also appear to be modified for absorption during the first two weeks after birth. Although goblet cells and Paneth cells are present during the suckling period, they do not comprise a significant population in the intestinal epithelium until after weaning. In contrast to the small intestine, goblet cells are numerous in the colon by the ninth postnatal day. The significance of macromolecular absorption and the possibility of passive immunity being transmitted in the opossum during suckling are discussed and related to similar events that occur in the slckling young of several eutherian species. The possible functional significance of two large membranes that develop in the lamina propria of the intestines after weaning also is discussed."}
{"id": "PMID:190200", "title": "Histochemical characteristics and contractile properties of the spinotrapezius muscle in the rat and the mouse.", "content": "In the spinotrapezius muscle of the rat and the mouse approximately equal proportions of A,B and C fibres are present. The spinotrapezius therefore contains a lower proportion of B fibres than are known to be present in soleus, but a higher proportion than in tibialis anterior. These results are consistent with the functional properties of the muscles, for the values for isometric twitch contraction time, the half relaxation time, and the twitch summation frequency of the spinotrapezius are also intermediate between those of soleus and tibialis anterior. The present experiments support the view that the proportion of B fibres to A and C fibres govern the overall functional characteristics of mammalian muscles.", "contents": "Histochemical characteristics and contractile properties of the spinotrapezius muscle in the rat and the mouse. In the spinotrapezius muscle of the rat and the mouse approximately equal proportions of A,B and C fibres are present. The spinotrapezius therefore contains a lower proportion of B fibres than are known to be present in soleus, but a higher proportion than in tibialis anterior. These results are consistent with the functional properties of the muscles, for the values for isometric twitch contraction time, the half relaxation time, and the twitch summation frequency of the spinotrapezius are also intermediate between those of soleus and tibialis anterior. The present experiments support the view that the proportion of B fibres to A and C fibres govern the overall functional characteristics of mammalian muscles."}
{"id": "PMID:190203", "title": "Lack of electrical interaction between proximal bundle branches and subjacent muscle.", "content": "Microelectrode techniques were used to assess the importance of subthreshold electrotonic interactions between the canine proximal bundle branches and adjacent septal myocardium, and vice versa. Bundle branch action potential duration, maximal rising velocity of phase O, current threshold requirements for all-or-none depolarization, transmembrane voltage, and spontaneous frequency were not altered by adjacent septal muscle activation. Activation of the proximal bundle branches did not change the transmembrane voltage of immediately subjacent muscle cells; likewise, all-or-none activation of ventricular septal muscle did not effect a voltage change in the overlying proximal bundle branches. We conclude that a high ohmic resistance barrier between proximal bundle branch and subjacent muscle precludes significant electrotonic interactions between these neighboring structures.", "contents": "Lack of electrical interaction between proximal bundle branches and subjacent muscle. Microelectrode techniques were used to assess the importance of subthreshold electrotonic interactions between the canine proximal bundle branches and adjacent septal myocardium, and vice versa. Bundle branch action potential duration, maximal rising velocity of phase O, current threshold requirements for all-or-none depolarization, transmembrane voltage, and spontaneous frequency were not altered by adjacent septal muscle activation. Activation of the proximal bundle branches did not change the transmembrane voltage of immediately subjacent muscle cells; likewise, all-or-none activation of ventricular septal muscle did not effect a voltage change in the overlying proximal bundle branches. We conclude that a high ohmic resistance barrier between proximal bundle branch and subjacent muscle precludes significant electrotonic interactions between these neighboring structures."}
{"id": "PMID:190204", "title": "cAMP in temperature- and ADH-regulating centers after thermal stress.", "content": "cAMP concentrations in temperature-regulating sites of the brain and plasma osmolality were measured after exposure of male rats to 36 degrees C and 37-42% rh. for 10, 20, or 30 min. Plasma osmolality was affected by none of the heat exposures. In both the preoptic area and the posterior medial hypothalamus, cAMP concentrations were increased compared to controls, after 10, 20 and 30 min of heat exposure. In the supraoptic-paraventricular nuclei, neither 10 nor 20 min of exposure resulted in augmented cAMP concentrations; but after 30 min of heat exposure, cAMP levels in these nuclei were significantly greater than in controls. Neurohypophysial cAMP concentrations were increased after both 10 and 30 min of exposure. Cerebral cortical cAMP concentrations were not affected by thermal stress. It is concluded that cAMP is involved in the neural mechanisms which are brought into play to regulate body temperature during acute heat exposure. The significance of this involvement and its relation to the overall temperature-regulating mechanisms of the body are discussed.", "contents": "cAMP in temperature- and ADH-regulating centers after thermal stress. cAMP concentrations in temperature-regulating sites of the brain and plasma osmolality were measured after exposure of male rats to 36 degrees C and 37-42% rh. for 10, 20, or 30 min. Plasma osmolality was affected by none of the heat exposures. In both the preoptic area and the posterior medial hypothalamus, cAMP concentrations were increased compared to controls, after 10, 20 and 30 min of heat exposure. In the supraoptic-paraventricular nuclei, neither 10 nor 20 min of exposure resulted in augmented cAMP concentrations; but after 30 min of heat exposure, cAMP levels in these nuclei were significantly greater than in controls. Neurohypophysial cAMP concentrations were increased after both 10 and 30 min of exposure. Cerebral cortical cAMP concentrations were not affected by thermal stress. It is concluded that cAMP is involved in the neural mechanisms which are brought into play to regulate body temperature during acute heat exposure. The significance of this involvement and its relation to the overall temperature-regulating mechanisms of the body are discussed."}
{"id": "PMID:190205", "title": "Neonatal chest wall afferents and regulation of respiration.", "content": "We have studied two groups of eight preterm infants, relating chest wall afferent information to respiratory timing. Rib cage and abdominal motion were monitored by magnetometers and flow and tidal volume via a face mask. In the first group, studies were done in REM sleep when spontaneously occurring distortion of the rib cage occurred and a significant linear relationship between the rate of distortion of the chest wall and shortening of the inspiratory time (Ti) was found in all infants. Reduction in this distortion by the use of continuous positive airway pressure (CPAP) or continuous negative pressure at the body surface (CNeg) was associated with a significant (P less than 0.01) lengthening of Ti. Absence of changes in Ti when pressure was applied in quiet sleep suggested that lung volume or chemical changes were not involved. In the second group of infants we artificially generated the afferent inflow by using vibratory stimuli applied in one intercostal interspace and produced a significant (P less than 0.05) shortening in Ti. We suggest that the distortion of the rib cage in REM sleep generates afferent information from intercostal muscle spindles that is related to the rate of distortion and this, via a supraspinal reflex, inhibits phrenic motoneuron discharge. It may then be of importance in the etiology of apneic episodes in these infants. Applied pressure may be of benefit because it reduces an inhibitory afferent inflow.", "contents": "Neonatal chest wall afferents and regulation of respiration. We have studied two groups of eight preterm infants, relating chest wall afferent information to respiratory timing. Rib cage and abdominal motion were monitored by magnetometers and flow and tidal volume via a face mask. In the first group, studies were done in REM sleep when spontaneously occurring distortion of the rib cage occurred and a significant linear relationship between the rate of distortion of the chest wall and shortening of the inspiratory time (Ti) was found in all infants. Reduction in this distortion by the use of continuous positive airway pressure (CPAP) or continuous negative pressure at the body surface (CNeg) was associated with a significant (P less than 0.01) lengthening of Ti. Absence of changes in Ti when pressure was applied in quiet sleep suggested that lung volume or chemical changes were not involved. In the second group of infants we artificially generated the afferent inflow by using vibratory stimuli applied in one intercostal interspace and produced a significant (P less than 0.05) shortening in Ti. We suggest that the distortion of the rib cage in REM sleep generates afferent information from intercostal muscle spindles that is related to the rate of distortion and this, via a supraspinal reflex, inhibits phrenic motoneuron discharge. It may then be of importance in the etiology of apneic episodes in these infants. Applied pressure may be of benefit because it reduces an inhibitory afferent inflow."}
{"id": "PMID:190207", "title": "Galactose transport in Salmonella typhimurium.", "content": "We have studied the various systems by which galactose can be transported in Salmonella typhimurium, in particular the specific galactose permease (GP). Mutants that contain GP as the sole galactose transport system have been isolated, and starting from these mutants we have been able to select point mutants that lack GP. The galP mutation maps close to another mutation, which results in the constitutive synthesis of GP, but is not linked to galR. Growth of wild-type strains on glaactose induces GP but not the beta-methylgalactoside permease (MGP). Strains lacking GP are able to grow slowly on galactose, and MGP is induced; however, D-fucose is a much better inducer of MGP. Induction of GP or MGP is not prevented by a pts mutation, although this mutation changes the apparent Km of MGP for galactose. pts mutations have no effect on GP. GP has a rather broad specificity: galactose, glucose, mannose, fucose, 2-deoxygalactose, and 2-deoxyglucose are substrates, but only galactose and fucose can induce this transport system.", "contents": "Galactose transport in Salmonella typhimurium. We have studied the various systems by which galactose can be transported in Salmonella typhimurium, in particular the specific galactose permease (GP). Mutants that contain GP as the sole galactose transport system have been isolated, and starting from these mutants we have been able to select point mutants that lack GP. The galP mutation maps close to another mutation, which results in the constitutive synthesis of GP, but is not linked to galR. Growth of wild-type strains on glaactose induces GP but not the beta-methylgalactoside permease (MGP). Strains lacking GP are able to grow slowly on galactose, and MGP is induced; however, D-fucose is a much better inducer of MGP. Induction of GP or MGP is not prevented by a pts mutation, although this mutation changes the apparent Km of MGP for galactose. pts mutations have no effect on GP. GP has a rather broad specificity: galactose, glucose, mannose, fucose, 2-deoxygalactose, and 2-deoxyglucose are substrates, but only galactose and fucose can induce this transport system."}
{"id": "PMID:190208", "title": "Reduction of iron and synthesis of protoheme by Spirillum itersonii and other organisms.", "content": "Membranes from Spirillum itersonii reduce ferric iron to ferrous iron with reduced nicotinamide adenine dinucleotide or succinate as a source of reductant. Iron reduction was measured spectrophotometrically at 562 nm using ferrozine, which chelates ferrous iron specifically. Reduced nicotinamide adenine dinucleotide or succinate was also effective as a source of iron. The effects of respiratory inhibitors suggested that reduction of iron occurs at one or more sites on the respiratory chain before cytochrome c. Reduction of iron and synthesis of protoheme with the physiological reductants were also observed with crude extracts of other bacteria, including Rhodopseudomonas spheroides, Rhodopseudomonas capsulata, Paracoccus denitrificans, and Escherichia coli. The effect of oxygen upon reduction of iron and formation of protoheme was examined with membranes from S. itersonii, using succinate as a source of reductant. Both systems were inhibited by oxygen, but this effect was completely reversed by addition of antimycin A. We conclude that reduced components of the respiratory chain serve as reductants for ferric iron, but with oxygen present they are oxidized preferentially by the successive members of the chain. This could be a mechanism for regulating synthesis of heme and cytochrome by oxygen.", "contents": "Reduction of iron and synthesis of protoheme by Spirillum itersonii and other organisms. Membranes from Spirillum itersonii reduce ferric iron to ferrous iron with reduced nicotinamide adenine dinucleotide or succinate as a source of reductant. Iron reduction was measured spectrophotometrically at 562 nm using ferrozine, which chelates ferrous iron specifically. Reduced nicotinamide adenine dinucleotide or succinate was also effective as a source of iron. The effects of respiratory inhibitors suggested that reduction of iron occurs at one or more sites on the respiratory chain before cytochrome c. Reduction of iron and synthesis of protoheme with the physiological reductants were also observed with crude extracts of other bacteria, including Rhodopseudomonas spheroides, Rhodopseudomonas capsulata, Paracoccus denitrificans, and Escherichia coli. The effect of oxygen upon reduction of iron and formation of protoheme was examined with membranes from S. itersonii, using succinate as a source of reductant. Both systems were inhibited by oxygen, but this effect was completely reversed by addition of antimycin A. We conclude that reduced components of the respiratory chain serve as reductants for ferric iron, but with oxygen present they are oxidized preferentially by the successive members of the chain. This could be a mechanism for regulating synthesis of heme and cytochrome by oxygen."}
{"id": "PMID:190209", "title": "Evidence for stable messenger ribonucleic acid during sporulation and enterotoxin synthesis by Clostridium perfringens type A.", "content": "Stable messenger ribonucleic acid (mRNA) was shown to be involved in both enterotoxin synthesis and synthesis of other spore coat proteins in Clostridium perfringens. When used at a concentration that inhibited [14C]uracil incorporation, rifampin, a specific inhibitor of deoxyribonucleic acid-dependent RNA polymerase, prevented incorporation of a mixture of labeled amnoo acids by 3-h sporulating cells. At that time, enterotoxin protein was first detectable and cells were primarily at stage II or III of sporulation. When rifampin or streptolydigin was added to 5-h sporulating cells, which were primarily at stage IV or V and had significant toxin levels, incorporation of labeled amino acids continued through 30 min despite its presence. Rifampin also failed to prevent the specific synthesis of enterotoxin, a structural protein of the spore coat. The half-life of enterotoxin RNA was estimated to be at least 58 min. When cell extracts from 5-h sporulating cells that had been exposed to 3H-labeled amino acids for 10 min were subjected to electrophoresis on polyacrylamide gels and the gels were subsequently analyzed for radioactivity, two major peaks of radioactivity were obtained. The two peaks corresponded to enterotoxin and another spore coat protein(s). Similar results were obtained when the cells had been preincubated for 60 min with rifampin before label addition, indicating the functioning of stable mRNA.", "contents": "Evidence for stable messenger ribonucleic acid during sporulation and enterotoxin synthesis by Clostridium perfringens type A. Stable messenger ribonucleic acid (mRNA) was shown to be involved in both enterotoxin synthesis and synthesis of other spore coat proteins in Clostridium perfringens. When used at a concentration that inhibited [14C]uracil incorporation, rifampin, a specific inhibitor of deoxyribonucleic acid-dependent RNA polymerase, prevented incorporation of a mixture of labeled amnoo acids by 3-h sporulating cells. At that time, enterotoxin protein was first detectable and cells were primarily at stage II or III of sporulation. When rifampin or streptolydigin was added to 5-h sporulating cells, which were primarily at stage IV or V and had significant toxin levels, incorporation of labeled amino acids continued through 30 min despite its presence. Rifampin also failed to prevent the specific synthesis of enterotoxin, a structural protein of the spore coat. The half-life of enterotoxin RNA was estimated to be at least 58 min. When cell extracts from 5-h sporulating cells that had been exposed to 3H-labeled amino acids for 10 min were subjected to electrophoresis on polyacrylamide gels and the gels were subsequently analyzed for radioactivity, two major peaks of radioactivity were obtained. The two peaks corresponded to enterotoxin and another spore coat protein(s). Similar results were obtained when the cells had been preincubated for 60 min with rifampin before label addition, indicating the functioning of stable mRNA."}
{"id": "PMID:190210", "title": "Control of morphogenesis in Arthrobacter crystallopoiets: effect of cyclic adenosine 3',5'-monophosphate.", "content": "The intracellular levels of cyclic adenosine 3',5'-monophosphate (cyclic AMP) were measured at various intervals during growth and morphogenesis in Arthrobacter crystallopoietes. Cyclic AMP levels remained relatively constant throughout growth in spherical cells grown in glucose-based media. Immediately after inoculation of spheres from glucose- to succinate-containing media, a 30-fold increase in intracellular cyclic AMP was detected. This dramatic rise in cyclic AMP preceded the observed change in cellular morphology from spheres to rods. The cyclic AMP level in rod-shaped cells rapidly dropped to a relatively stable concentration during the exponential growth phase. At the onset of stationary phase and rod-to-sphere morphological transition, a second peak of cyclic AMP was observed. Neither of these two peaks was detectable in a morphogenetic mutant that grew only as spheres. The intracellular levels of cyclic AMP in this mutant remained constant throughout exponential growth and decreased slightly during stationary phase. Effects of exogenously added cyclic nucleotides and their derivatives to both parent and mutant cultures were investigated. The data presented indicate that dramatic changes in intracellular cyclic AMP levels occur just before the morphological transitions characteristic of the morphogenetic cycle in A. crystallopoietes. It is suggested that cyclic AMP is a contributing factor in the regulatory phenomenon associated with morphogenesis in this bacterium.", "contents": "Control of morphogenesis in Arthrobacter crystallopoiets: effect of cyclic adenosine 3',5'-monophosphate. The intracellular levels of cyclic adenosine 3',5'-monophosphate (cyclic AMP) were measured at various intervals during growth and morphogenesis in Arthrobacter crystallopoietes. Cyclic AMP levels remained relatively constant throughout growth in spherical cells grown in glucose-based media. Immediately after inoculation of spheres from glucose- to succinate-containing media, a 30-fold increase in intracellular cyclic AMP was detected. This dramatic rise in cyclic AMP preceded the observed change in cellular morphology from spheres to rods. The cyclic AMP level in rod-shaped cells rapidly dropped to a relatively stable concentration during the exponential growth phase. At the onset of stationary phase and rod-to-sphere morphological transition, a second peak of cyclic AMP was observed. Neither of these two peaks was detectable in a morphogenetic mutant that grew only as spheres. The intracellular levels of cyclic AMP in this mutant remained constant throughout exponential growth and decreased slightly during stationary phase. Effects of exogenously added cyclic nucleotides and their derivatives to both parent and mutant cultures were investigated. The data presented indicate that dramatic changes in intracellular cyclic AMP levels occur just before the morphological transitions characteristic of the morphogenetic cycle in A. crystallopoietes. It is suggested that cyclic AMP is a contributing factor in the regulatory phenomenon associated with morphogenesis in this bacterium."}
{"id": "PMID:190211", "title": "Constitutive mutations in the controlling site region of the araBAD operon of Escherichia coli B/r that decrease sensitivity to catabolite repression.", "content": "Strains of Escherichia coli B/r containing a deletion of the regulatory gene araC are Ara-. Slow-growing revertants of these strains were isolated and designated aralc because they contain a second mutation in a controlling site, aral, that allows for a low level of constitutive expression of the araBAD operon (Englesbert et al., 1969). We mutagenized aralc delta C strains and selected mutants that grow faster in mineral L-arabinose medium. The new mutations, called araXc, map very close to the original aralc mutations and are in the controlling site region between araB and araC. The aralcXc delta C strains have a higher constitutive level of expression of the araBAD operon than the aralc delta C parents. The araXc mutations are cis acting and decrease the araBAD operon's sensitivity to catabolite repression. The araBAD operon is expressed equally well in ara delta C and ara C cya crp backgrounds. The repressor form of ara C protein is able to repress the constitutive synthesis due to the ara Xc allele.", "contents": "Constitutive mutations in the controlling site region of the araBAD operon of Escherichia coli B/r that decrease sensitivity to catabolite repression. Strains of Escherichia coli B/r containing a deletion of the regulatory gene araC are Ara-. Slow-growing revertants of these strains were isolated and designated aralc because they contain a second mutation in a controlling site, aral, that allows for a low level of constitutive expression of the araBAD operon (Englesbert et al., 1969). We mutagenized aralc delta C strains and selected mutants that grow faster in mineral L-arabinose medium. The new mutations, called araXc, map very close to the original aralc mutations and are in the controlling site region between araB and araC. The aralcXc delta C strains have a higher constitutive level of expression of the araBAD operon than the aralc delta C parents. The araXc mutations are cis acting and decrease the araBAD operon's sensitivity to catabolite repression. The araBAD operon is expressed equally well in ara delta C and ara C cya crp backgrounds. The repressor form of ara C protein is able to repress the constitutive synthesis due to the ara Xc allele."}
{"id": "PMID:190212", "title": "Functional mosaicism of membrane proteins in vesicles of Escherichia coli.", "content": "Membrane vesicles of Escherichia coli prepared by osmotic lysis of lysozyme ethylenediaminetetracetate (EDTA) spheroplasts have approximately 60% of the total membrane-bound reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase (ED 1.6.99.3) and Mg2+-adenosine triphosphatase (ATPase) (EC 3.6.1.3) activities exposed on the outer surface of the inner membrane. Absorption of these vesicles with antiserum prepared against the purified soluble Mg2+-ATPase resulted in agglutination of approximately 95% of the inner membrane vesicles, as determined by dehydrogenase activity, and about 50% of the total membrane protein. The unagglutinated vesicles lacked all dehydrogenase activity and may consist of outer membrane. Lysozyme-EDTA vesicles actively transported calcium ion, using either NADH or adenosine 5'-triphosphate (ATP) as energy source. However, neither D-lactate nor reduced phenazine methosulfate energized calcium uptake, suggesting that the observed calcium uptake was not due to a small population of everted vesicles. Transport of calcium driven by either NADH or ATP was inhibited by simultaneous addition of D-lactate or reduced phenazine methosulfate. Proline transport driven by D-lactate oxidation was inhibited by either NADH oxidation or ATP hydrolysis. These results suggest that the portion of the total population of vesicles capable of active transport, i.e., the inner membrane vesicles, are functionally a homogeneous population but cannot be categorized as either right-side-out or everted, since activities normally associated with only one side of the inner membrane can be found on both sides of the membrane of these vesicles. Moreover, the data indicate that oxidation of NADH or hydrolysis of ATP by externally localized NADH dehydrogenase or Mg2+-ATPase establishes a protonmotive force of the opposite polarity from that established through D-lactate oxidation.", "contents": "Functional mosaicism of membrane proteins in vesicles of Escherichia coli. Membrane vesicles of Escherichia coli prepared by osmotic lysis of lysozyme ethylenediaminetetracetate (EDTA) spheroplasts have approximately 60% of the total membrane-bound reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase (ED 1.6.99.3) and Mg2+-adenosine triphosphatase (ATPase) (EC 3.6.1.3) activities exposed on the outer surface of the inner membrane. Absorption of these vesicles with antiserum prepared against the purified soluble Mg2+-ATPase resulted in agglutination of approximately 95% of the inner membrane vesicles, as determined by dehydrogenase activity, and about 50% of the total membrane protein. The unagglutinated vesicles lacked all dehydrogenase activity and may consist of outer membrane. Lysozyme-EDTA vesicles actively transported calcium ion, using either NADH or adenosine 5'-triphosphate (ATP) as energy source. However, neither D-lactate nor reduced phenazine methosulfate energized calcium uptake, suggesting that the observed calcium uptake was not due to a small population of everted vesicles. Transport of calcium driven by either NADH or ATP was inhibited by simultaneous addition of D-lactate or reduced phenazine methosulfate. Proline transport driven by D-lactate oxidation was inhibited by either NADH oxidation or ATP hydrolysis. These results suggest that the portion of the total population of vesicles capable of active transport, i.e., the inner membrane vesicles, are functionally a homogeneous population but cannot be categorized as either right-side-out or everted, since activities normally associated with only one side of the inner membrane can be found on both sides of the membrane of these vesicles. Moreover, the data indicate that oxidation of NADH or hydrolysis of ATP by externally localized NADH dehydrogenase or Mg2+-ATPase establishes a protonmotive force of the opposite polarity from that established through D-lactate oxidation."}
{"id": "PMID:190213", "title": "Gluconeogenesis in Saccharomyces cerevisiae: determination of fructose-1,6-bisphosphatase activity in cells grown in the presence of glycolytic carbon sources.", "content": "The activity of fructose-1,6-bisphosphatase (FBP), a gluconeogenic enzyme, was determined in wild-type Saccharomyces cerevisiae X2180 grown in the presence of the glycolytic carbon sources, glucose, fructose, and galactose. The activities of phosphofructokinase (PFK), a glycolytic enzyme, and phosphoglucose isomerase (PGI), an enzyme functioning both in glycolysis and gluconeogenesis, were determined for purposes of comparison. A measurable amount of FBP activity was present in 20-h-old cells grown with moderate shaking in 1% glucose-nutrient or minimal medium. This activity increased significantly in 40 and 60-h-old cells. Similar levels of FBP activity were also present in 20-, 40-, and 60-h-old cells grown in 1% fructose-nutrient medium. A higher level of FBP activity was present in 20-h-old cells grown in 1% galactose-nutrient medium than in 20-h-old cells grown in 1% glucose- or fructose-nutrient medium. The FBP activity in glucose- or fructose-grown cells was higher than the corresponding activity in cells grown under similar conditions for 40 and 60 h in the presence of ethanol, a gluconeogenic carbon source. The PFK activity was significantly less in galactose- and ethanol-grown cells. The PGI activity was relatively constant in 20-, 40-, and 60-h-old cells grown in the presence of glucose, fructose, and galactose, but this activity was reduced approximately 50% in ethanol-grown cells. It is concluded from these results that, depending upon the concentration of carbon source and the time of incubation, FBP, a strictly gloconeogenic enzyme, is synthesized by S. cerevisiae grown in the presence of glycolytic carbon sources.", "contents": "Gluconeogenesis in Saccharomyces cerevisiae: determination of fructose-1,6-bisphosphatase activity in cells grown in the presence of glycolytic carbon sources. The activity of fructose-1,6-bisphosphatase (FBP), a gluconeogenic enzyme, was determined in wild-type Saccharomyces cerevisiae X2180 grown in the presence of the glycolytic carbon sources, glucose, fructose, and galactose. The activities of phosphofructokinase (PFK), a glycolytic enzyme, and phosphoglucose isomerase (PGI), an enzyme functioning both in glycolysis and gluconeogenesis, were determined for purposes of comparison. A measurable amount of FBP activity was present in 20-h-old cells grown with moderate shaking in 1% glucose-nutrient or minimal medium. This activity increased significantly in 40 and 60-h-old cells. Similar levels of FBP activity were also present in 20-, 40-, and 60-h-old cells grown in 1% fructose-nutrient medium. A higher level of FBP activity was present in 20-h-old cells grown in 1% galactose-nutrient medium than in 20-h-old cells grown in 1% glucose- or fructose-nutrient medium. The FBP activity in glucose- or fructose-grown cells was higher than the corresponding activity in cells grown under similar conditions for 40 and 60 h in the presence of ethanol, a gluconeogenic carbon source. The PFK activity was significantly less in galactose- and ethanol-grown cells. The PGI activity was relatively constant in 20-, 40-, and 60-h-old cells grown in the presence of glucose, fructose, and galactose, but this activity was reduced approximately 50% in ethanol-grown cells. It is concluded from these results that, depending upon the concentration of carbon source and the time of incubation, FBP, a strictly gloconeogenic enzyme, is synthesized by S. cerevisiae grown in the presence of glycolytic carbon sources."}
{"id": "PMID:190214", "title": "Isolation of the major glycoprotein from plasma membranes of an ascites hepatoma AH 66.", "content": "Plasma membranes were isolated from AH 66 cells, some of which had been labeled with [14C]glucosamine, by the following procedure: homogenization of cells which had been hardened by treatment with Zn ions, fractionation of the homogenate by sucrose density gradient centrifugation and purification of the membranes by partition in an aqueous two-phase polymer system. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS) of the plasma membranes and subsequent staining of the gel for protein and carbohydrate, and determination of radioactivity on the gel eluates indicated the presence of at least 10 bands of glycoproteins. The major band contained 27% of the total radioactivity incorporated into the plasma membranes and was most heavily stained with the periodate-Schiff reagent. To isolate the major glycoprotein, the membranes were solubilized with 0.6 M lithium diiodosalicylate containing 0.5% Triton X-100, then the solution was treated with phenol. The major glycoprotein, obtained in the aqueous phase, was further purified mainly by repeated chromatographies on Sepharose 6B. The purified preparation was practically homogeneous on SDS-polyacrylamide gel electrophoresis, as judged by radioactivity determination and by carbohydrate staining, but contained small amounts of carbohydrate-free proteins. The major glycoprotein had an apparent molecular weight of 160,000, as determined by SDS-polyacrylamide gel electrophoresis. The final preparation contained about 44% carbohydrate on a weight basis, and the carbohydrate moiety was composed of glucosamine, galactosamine, galactose, mannose, fucose, and sialic acid. This composition indicates that the major glycoprotein contains both N- and O-glycosidically linked oligosaccharide moieties.", "contents": "Isolation of the major glycoprotein from plasma membranes of an ascites hepatoma AH 66. Plasma membranes were isolated from AH 66 cells, some of which had been labeled with [14C]glucosamine, by the following procedure: homogenization of cells which had been hardened by treatment with Zn ions, fractionation of the homogenate by sucrose density gradient centrifugation and purification of the membranes by partition in an aqueous two-phase polymer system. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS) of the plasma membranes and subsequent staining of the gel for protein and carbohydrate, and determination of radioactivity on the gel eluates indicated the presence of at least 10 bands of glycoproteins. The major band contained 27% of the total radioactivity incorporated into the plasma membranes and was most heavily stained with the periodate-Schiff reagent. To isolate the major glycoprotein, the membranes were solubilized with 0.6 M lithium diiodosalicylate containing 0.5% Triton X-100, then the solution was treated with phenol. The major glycoprotein, obtained in the aqueous phase, was further purified mainly by repeated chromatographies on Sepharose 6B. The purified preparation was practically homogeneous on SDS-polyacrylamide gel electrophoresis, as judged by radioactivity determination and by carbohydrate staining, but contained small amounts of carbohydrate-free proteins. The major glycoprotein had an apparent molecular weight of 160,000, as determined by SDS-polyacrylamide gel electrophoresis. The final preparation contained about 44% carbohydrate on a weight basis, and the carbohydrate moiety was composed of glucosamine, galactosamine, galactose, mannose, fucose, and sialic acid. This composition indicates that the major glycoprotein contains both N- and O-glycosidically linked oligosaccharide moieties."}
{"id": "PMID:190215", "title": "Chemical characterization of the serum very low density and high density lipoproteins from bullfrog, Rana catesbeiana.", "content": "The chemical properties of very low density and high density lipoproteins of adult bullfrog serum were determined. This serum contained extremely low levels of both very low density lipoprotein (10-30 mg/100 ml) and high density lipoprotein (5-10 mg/100 ml). The constituents of very low density lipoprotein, on a weight percentage basis, were found to be 48.1% triglyceride, 17.3% cholesterol ester, 8.8% cholesterol, 11.6% phospholipid, and 12% protein. These constituents were also present in high density lipoprotein with weight percentage values of 3.7%, 19.3%, 11.9%, 25.2%, and 36.8%, respectively. The fatty acid compositions of the triglycerides, cholesterol esters, and phosphatidylcholine were quite similar in the very low density lipoprotein and high density lipoprotein. However, shingomyelin fatty acid composition was appreciably different in the two lipoproteins. Disc gel electrophoresis in sodium dodecyl sulfate-polyacrylamide gels produced patterns with one major (approximate molecular weight, 7,000) and several minor bands for the apoprotein of very low density lipoprotein and one major (approximate molecular weight, 28,000) and several minor bands for that of high density lipoprotein.", "contents": "Chemical characterization of the serum very low density and high density lipoproteins from bullfrog, Rana catesbeiana. The chemical properties of very low density and high density lipoproteins of adult bullfrog serum were determined. This serum contained extremely low levels of both very low density lipoprotein (10-30 mg/100 ml) and high density lipoprotein (5-10 mg/100 ml). The constituents of very low density lipoprotein, on a weight percentage basis, were found to be 48.1% triglyceride, 17.3% cholesterol ester, 8.8% cholesterol, 11.6% phospholipid, and 12% protein. These constituents were also present in high density lipoprotein with weight percentage values of 3.7%, 19.3%, 11.9%, 25.2%, and 36.8%, respectively. The fatty acid compositions of the triglycerides, cholesterol esters, and phosphatidylcholine were quite similar in the very low density lipoprotein and high density lipoprotein. However, shingomyelin fatty acid composition was appreciably different in the two lipoproteins. Disc gel electrophoresis in sodium dodecyl sulfate-polyacrylamide gels produced patterns with one major (approximate molecular weight, 7,000) and several minor bands for the apoprotein of very low density lipoprotein and one major (approximate molecular weight, 28,000) and several minor bands for that of high density lipoprotein."}
{"id": "PMID:190216", "title": "Cardiac adenosine 3':5'-monophosphate. Free and bound forms in the isolated rat atrium.", "content": "Adenosine 3':5'-monophosphate (cyclic AMP), a mediator of hormone action in a variety of tissues, has been measured in its free and bound forms in intact cardiac tissue. We have used a rapid high dilution technique which involves tissue homogenization, subcellular fractionation, and separation of bound from free cyclic AMP by Millopore filtration. The precision of this method is dependent upon minimization of binding and dissociation of cyclic AMP that occur during the preparation and handling of tissue homogenates. In each experiment, a tracer of cyclic [3H]AMP prebound to isolated cardiac binding protein was freed of unbound cyclic [3H]AMP by Sephadex gel filtration and added to the tissue just prior to homogenization in cold EDTA buffer. This tracer was therefore treated identically to the sample through all subsequent dilution, fractionation, and filtration procedures, and provided an acurate internal monitor for total cyclic AMP dissociation during the course of the free-bound determination. Each tissue sample was then individually corrected for dissociation. Rapid dilution to produce a 1:1000 homogenate was found to lower endogenous cyclic AMP levels sufficiently to make binding (or rebinding) during the procedure negligible (less than 5%). Spontaneously beating rat right atria (controls) contained 5.96 +/- 0.28 pmol of cyclic AMP/mg of protein (n = 19) of which 41 and 14% were bound to soluble and particulate proteins, respectively. The remaining cyclic AMP was free. Pretreatment of the tissue with 1 muM isoproterenol (30 s at 30 degrees) increased both the bound and free forms of cyclic AMP (n = 8). While free cyclic AMP increased 420% with the catecholamine, the bound forms increased 240% (soluble) and 60% (particulate). Similar results were obtained when atria (n = 6) were treated with the phosphodiesterase inhibitor, methylisobutylxanthine (0.5 mM, 10 min at 30 degrees). When both agents were used together, cyclic AMP bound to soluble proteins was elevated 4-fold over control while free cyclic AMP increased 27-fold (n = 7), indicating saturation of the soluble sites. It could be calculated that less than one-third of these sites are occupied in the unstimulated cell. These sites may represent the R subunit of cyclic AMP-dependent protein kinase. The data suggest that half-maximal binding in vivo occurs at an intracellular free cyclic AMP concentration of about 1 muM.", "contents": "Cardiac adenosine 3':5'-monophosphate. Free and bound forms in the isolated rat atrium. Adenosine 3':5'-monophosphate (cyclic AMP), a mediator of hormone action in a variety of tissues, has been measured in its free and bound forms in intact cardiac tissue. We have used a rapid high dilution technique which involves tissue homogenization, subcellular fractionation, and separation of bound from free cyclic AMP by Millopore filtration. The precision of this method is dependent upon minimization of binding and dissociation of cyclic AMP that occur during the preparation and handling of tissue homogenates. In each experiment, a tracer of cyclic [3H]AMP prebound to isolated cardiac binding protein was freed of unbound cyclic [3H]AMP by Sephadex gel filtration and added to the tissue just prior to homogenization in cold EDTA buffer. This tracer was therefore treated identically to the sample through all subsequent dilution, fractionation, and filtration procedures, and provided an acurate internal monitor for total cyclic AMP dissociation during the course of the free-bound determination. Each tissue sample was then individually corrected for dissociation. Rapid dilution to produce a 1:1000 homogenate was found to lower endogenous cyclic AMP levels sufficiently to make binding (or rebinding) during the procedure negligible (less than 5%). Spontaneously beating rat right atria (controls) contained 5.96 +/- 0.28 pmol of cyclic AMP/mg of protein (n = 19) of which 41 and 14% were bound to soluble and particulate proteins, respectively. The remaining cyclic AMP was free. Pretreatment of the tissue with 1 muM isoproterenol (30 s at 30 degrees) increased both the bound and free forms of cyclic AMP (n = 8). While free cyclic AMP increased 420% with the catecholamine, the bound forms increased 240% (soluble) and 60% (particulate). Similar results were obtained when atria (n = 6) were treated with the phosphodiesterase inhibitor, methylisobutylxanthine (0.5 mM, 10 min at 30 degrees). When both agents were used together, cyclic AMP bound to soluble proteins was elevated 4-fold over control while free cyclic AMP increased 27-fold (n = 7), indicating saturation of the soluble sites. It could be calculated that less than one-third of these sites are occupied in the unstimulated cell. These sites may represent the R subunit of cyclic AMP-dependent protein kinase. The data suggest that half-maximal binding in vivo occurs at an intracellular free cyclic AMP concentration of about 1 muM."}
{"id": "PMID:190217", "title": "Metabolism of 5-fluorouracil in sensitive and resistant Novikoff hepatoma cells.", "content": "N1-S1/FdUrd Novikoff hepatoma cells, which lack thymidine kinase activity, are resistant to 5-fluorouracil (FUra) as well as 5-fluorodeoxyuridine (FdUrd), suggesting that the pathway, FUra leads to FdUrd leads to FdUMP, is utilized for the conversion of FUra to FdUMP. However, the inhibition of thymidylate synthetase activity, the presumed target of FdUMP, by 1 X 10(-4) M FUra in intact N1-S1 Novikoff hepatoma cells, which have significant levels of thymidine kinase activity, is completely eliminated by 5 X 10(-4) M hydroxyurea, which is a potent inhibitor of ribonucleotide reductase. These results imply that the formation of ribonucleotides and does not involve thymidine kinase. This apparent dichotomy can be explained by the fact that, in addition to the well known lack of thymidine kinase activity, [14C]FUra conversion to ribonucleotides is greatly depressed in the N1-S1/FdUrd cells. Hence, the formation of FdUMP from FUra in Novikoff hepatoma cells apparently proceeds primarily via the intermediate formation of ribonucleotides. The decreased conversion of FUra to ribonucleotides in N1-S1/FdUrd cells decreases not only the ability of the analog to inhibit DNA synthesis, but also its effect on RNA metabolism. FUra, at a concentration of 1 X 10(-5) M, inhibits rRNA maturation in N1-S1 cells, but not in N1-S1/FdUrd cells. Since N1-S1/FdUrd cells are completely resistant to 1 X 10(-5) M FUra, whereas N1-S1 cells are completely inhibited by 1 X 10(-5) M FUra, even in the presence of 1 X 10(-4) M thymidine, the effects of FUra on RNA metabolism appear to contribute significantly to the cytotoxicity of the analog at higher drug concentrations.", "contents": "Metabolism of 5-fluorouracil in sensitive and resistant Novikoff hepatoma cells. N1-S1/FdUrd Novikoff hepatoma cells, which lack thymidine kinase activity, are resistant to 5-fluorouracil (FUra) as well as 5-fluorodeoxyuridine (FdUrd), suggesting that the pathway, FUra leads to FdUrd leads to FdUMP, is utilized for the conversion of FUra to FdUMP. However, the inhibition of thymidylate synthetase activity, the presumed target of FdUMP, by 1 X 10(-4) M FUra in intact N1-S1 Novikoff hepatoma cells, which have significant levels of thymidine kinase activity, is completely eliminated by 5 X 10(-4) M hydroxyurea, which is a potent inhibitor of ribonucleotide reductase. These results imply that the formation of ribonucleotides and does not involve thymidine kinase. This apparent dichotomy can be explained by the fact that, in addition to the well known lack of thymidine kinase activity, [14C]FUra conversion to ribonucleotides is greatly depressed in the N1-S1/FdUrd cells. Hence, the formation of FdUMP from FUra in Novikoff hepatoma cells apparently proceeds primarily via the intermediate formation of ribonucleotides. The decreased conversion of FUra to ribonucleotides in N1-S1/FdUrd cells decreases not only the ability of the analog to inhibit DNA synthesis, but also its effect on RNA metabolism. FUra, at a concentration of 1 X 10(-5) M, inhibits rRNA maturation in N1-S1 cells, but not in N1-S1/FdUrd cells. Since N1-S1/FdUrd cells are completely resistant to 1 X 10(-5) M FUra, whereas N1-S1 cells are completely inhibited by 1 X 10(-5) M FUra, even in the presence of 1 X 10(-4) M thymidine, the effects of FUra on RNA metabolism appear to contribute significantly to the cytotoxicity of the analog at higher drug concentrations."}
{"id": "PMID:190218", "title": "Portein kinases in brown adipose tissue of developing rats. State of activation of protein kinase during development and cold exposure and its relationship to adenosine 3':5'-monophosphate, lipolysis, and heat production.", "content": "The addition of norepinephrine to brown fat in vitro produced a dose-dependent increase in the protein kinase activity ratio (the ratio of activity assayed without cAMP to that assayed with cAMP) in extracts subsequently prepared in the presence of 0.5 M NaCl. The ratio was slightly increased by insulin. The effects of norepinephrine were potentiated by theophylline and reduced by propranolol. There was a significant linear regression between protein kinase activity ratio and the rate of glycerol release for ratios between 0.32 and 0.52. Higher activity ratios were associated with a slight but nonsignificant increase in glycerol release. The relationship between the protein kinase activity ratio and the concentration of cAMP in brown fat could be expressed by simple saturation kinetics. There was a significant linear regression between the reciprocal of the concentration of cAMP in the tissue and the reciprocal of the activity ratio over the whole range of observed values. Exposure of 1-month-old rats to cold increased the protein kinase activity ratio in their brown fat. This confirms that activation of protein kinase is involved in the physiological response of a tissue to a specific environmental stimulus. As the rat became fully adapted to the cold, the activity ratio declined. The protein kinase activity ratio in brown fat was low in late fetuses but greatly increased immediately after birth and remained high for the next 2 weeks. During this period the ratio was not further increased by the injection of norepinephrine but was reduced after chemical sympathectomy. The activity ratio in brown fat fell during the 3rd and 4th weeks after birth. At this time injection of norepinephrine increased the ratio whereas chemical sympathectomy had little effect. These observations confirm that the stimulation of the tissue by the sympathetic nerves results in an activation of protein kinase and reflect the reduced requirement for heat production in brown fat as the animals grow.", "contents": "Portein kinases in brown adipose tissue of developing rats. State of activation of protein kinase during development and cold exposure and its relationship to adenosine 3':5'-monophosphate, lipolysis, and heat production. The addition of norepinephrine to brown fat in vitro produced a dose-dependent increase in the protein kinase activity ratio (the ratio of activity assayed without cAMP to that assayed with cAMP) in extracts subsequently prepared in the presence of 0.5 M NaCl. The ratio was slightly increased by insulin. The effects of norepinephrine were potentiated by theophylline and reduced by propranolol. There was a significant linear regression between protein kinase activity ratio and the rate of glycerol release for ratios between 0.32 and 0.52. Higher activity ratios were associated with a slight but nonsignificant increase in glycerol release. The relationship between the protein kinase activity ratio and the concentration of cAMP in brown fat could be expressed by simple saturation kinetics. There was a significant linear regression between the reciprocal of the concentration of cAMP in the tissue and the reciprocal of the activity ratio over the whole range of observed values. Exposure of 1-month-old rats to cold increased the protein kinase activity ratio in their brown fat. This confirms that activation of protein kinase is involved in the physiological response of a tissue to a specific environmental stimulus. As the rat became fully adapted to the cold, the activity ratio declined. The protein kinase activity ratio in brown fat was low in late fetuses but greatly increased immediately after birth and remained high for the next 2 weeks. During this period the ratio was not further increased by the injection of norepinephrine but was reduced after chemical sympathectomy. The activity ratio in brown fat fell during the 3rd and 4th weeks after birth. At this time injection of norepinephrine increased the ratio whereas chemical sympathectomy had little effect. These observations confirm that the stimulation of the tissue by the sympathetic nerves results in an activation of protein kinase and reflect the reduced requirement for heat production in brown fat as the animals grow."}
{"id": "PMID:190219", "title": "Transmission of the cytochrome c structural gene in horse-donkey crosses.", "content": "Donkey cytochrome c was shown to differ from horse cytochrome c by having a serine in position 47 rather than a threonine. The rest of the amino acid sequences are identical. Mules and hinnies, both males and females, carry equal amounts of horse and donkey cytochromes c. The same ratio is found in hinnies in preparations from heart tissue and from skeletal muscle. These results demonstrate that cytochrome c is transmitted in horse-donkey crosses as a simple Mendelian character which is neither sex-linked nor shows dominance. The cytochrome c gene is therefore located in the nuclear genome, as earlier shown to be the case for Saccharomyces iso-1-cytochrome c.", "contents": "Transmission of the cytochrome c structural gene in horse-donkey crosses. Donkey cytochrome c was shown to differ from horse cytochrome c by having a serine in position 47 rather than a threonine. The rest of the amino acid sequences are identical. Mules and hinnies, both males and females, carry equal amounts of horse and donkey cytochromes c. The same ratio is found in hinnies in preparations from heart tissue and from skeletal muscle. These results demonstrate that cytochrome c is transmitted in horse-donkey crosses as a simple Mendelian character which is neither sex-linked nor shows dominance. The cytochrome c gene is therefore located in the nuclear genome, as earlier shown to be the case for Saccharomyces iso-1-cytochrome c."}
{"id": "PMID:190220", "title": "Characterization and regulation of heart adenosine 3':5'-monophosphate-dependent protein kinase isozymes.", "content": "There is broad species variation in the type of cAMP-dependent protein kinase isozyme present in supernatant fractions of heart homogenates as determined by DEAE-cellulose chromatography, Isozyme I, which elutes at less than 0.1 M NaCl, is predominant in mouse and rat hearts; while isozyme II, which elutes at greater than 0.1 M NaCl, is the predominant type in beef and guinea pig. Human and rabbit hearts contain about equal amounts of the two types. The type I heart kinases are more easily dissociated into free regulatory and catalytic subunits by incubation with histone than are the type II kinases, and the separated regulatory and catalytic subunits of isozyme II of rat heart reassociate more rapidly than the subunits of isozyme I under the conditions used. The data from several experiments using rat heart indicate that the basal activity ratio of the protein kinase in crude extracts (approximately 0.15) is due mainly to basal endogenous cAMP and that cAMP elevation accounts entirely for the epinephrine effect on the enzyme. Addition of epinephrine and 1-methyl-3-isobutylxanthine to the perfusate causes a rapid (1 min) increase in cAMP, active supernatant protein kinase, and active phosphorylase in perfused hearts of both rat (mainly isozyme I) and guinea pig (mainly isozyme II). The elevation percentage in cAMP is about the same in the two species, but the increase in active protein kinase is greater in rat heart. If hearts from either animal are perfused continually (10 min) with epinephrine (0.8 muM) and 1-methyl-3-isobutylxanthine (10 muM), the cAMP level, active protein kinase, and active phosphorylase remain elevated. Likewise, all parameters return rapidly to the basal levels when epinephrine and 1-methyl-3-isobutylxanthin are removed. Most of the epinephrine effect on the rat heart supernatant kinase is retained at 0 degrees if cAMP is removed by Sephadex G-25 chromatography, although this procedure completely reverses the epinephrine effect in the guinea pig heart. The epinephrine effect on the rabbit heart kinase (approximately equal amounts of isozymes I and II) is partially reversed by Sephadex G-25. These species differences can be accounted for by differences in association-dissociation behavior of the isozymes in vitro. The data suggest that epinephrine causes activation of both isozymes. The activity present in the particulate fraction comprises nearly half of the total cAMP-dependent protein kinase activity in homogenates of rabbit heart. Triton X-100 extracts of low speed particulate fractions from hearts of each species tested, including rat heart, contain predominantly or entirely the type II isozyme, suggesting differences in intracellular distribution of the isozymes. The binding of the protein kinase to the particulate fraction is apparently due to the properties of the regulatory subunit component. Differences in topographical distribution of the isozymes could provide for differences in either physiological regulation or substrate specificity.", "contents": "Characterization and regulation of heart adenosine 3':5'-monophosphate-dependent protein kinase isozymes. There is broad species variation in the type of cAMP-dependent protein kinase isozyme present in supernatant fractions of heart homogenates as determined by DEAE-cellulose chromatography, Isozyme I, which elutes at less than 0.1 M NaCl, is predominant in mouse and rat hearts; while isozyme II, which elutes at greater than 0.1 M NaCl, is the predominant type in beef and guinea pig. Human and rabbit hearts contain about equal amounts of the two types. The type I heart kinases are more easily dissociated into free regulatory and catalytic subunits by incubation with histone than are the type II kinases, and the separated regulatory and catalytic subunits of isozyme II of rat heart reassociate more rapidly than the subunits of isozyme I under the conditions used. The data from several experiments using rat heart indicate that the basal activity ratio of the protein kinase in crude extracts (approximately 0.15) is due mainly to basal endogenous cAMP and that cAMP elevation accounts entirely for the epinephrine effect on the enzyme. Addition of epinephrine and 1-methyl-3-isobutylxanthine to the perfusate causes a rapid (1 min) increase in cAMP, active supernatant protein kinase, and active phosphorylase in perfused hearts of both rat (mainly isozyme I) and guinea pig (mainly isozyme II). The elevation percentage in cAMP is about the same in the two species, but the increase in active protein kinase is greater in rat heart. If hearts from either animal are perfused continually (10 min) with epinephrine (0.8 muM) and 1-methyl-3-isobutylxanthine (10 muM), the cAMP level, active protein kinase, and active phosphorylase remain elevated. Likewise, all parameters return rapidly to the basal levels when epinephrine and 1-methyl-3-isobutylxanthin are removed. Most of the epinephrine effect on the rat heart supernatant kinase is retained at 0 degrees if cAMP is removed by Sephadex G-25 chromatography, although this procedure completely reverses the epinephrine effect in the guinea pig heart. The epinephrine effect on the rabbit heart kinase (approximately equal amounts of isozymes I and II) is partially reversed by Sephadex G-25. These species differences can be accounted for by differences in association-dissociation behavior of the isozymes in vitro. The data suggest that epinephrine causes activation of both isozymes. The activity present in the particulate fraction comprises nearly half of the total cAMP-dependent protein kinase activity in homogenates of rabbit heart. Triton X-100 extracts of low speed particulate fractions from hearts of each species tested, including rat heart, contain predominantly or entirely the type II isozyme, suggesting differences in intracellular distribution of the isozymes. The binding of the protein kinase to the particulate fraction is apparently due to the properties of the regulatory subunit component. Differences in topographical distribution of the isozymes could provide for differences in either physiological regulation or substrate specificity."}
{"id": "PMID:190221", "title": "Regulation of 3-hydroxy-3-methylglutaryl coenzyme a reductase in minimal deviation hepatoma 7288C. Immunological measurements in hepatoma tissue culture cells.", "content": "The mechanism of action of serum lipoproteins and 25-hydroxycholesterol on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in hepatoma tissue culture (HTC) cells was investigated using antiserum against purified rat liver HMG-CoA reductase (Heller, R. A., and Shrewsbury, M. A. (1976)J. Biol. Chem. 251, 3815-3822). This antiserum cross-reacted with solubilized and membrane-bound HMG-CoA reductase from HTC cells. The enzymes from rat liver and HTC cells appeared antigenically identical. The increase in HMG-CoA reductase activity of HTC cells grown in medium which lacked serum lipoproteins was shown to be due to an increase in immunoprecipitable enzyme. In contrast, the 25-hydroxycholesterol suppression of reductase activity leads to a reduction in the antigenicity of the enzyme rather than a decrease in its number of molecules.", "contents": "Regulation of 3-hydroxy-3-methylglutaryl coenzyme a reductase in minimal deviation hepatoma 7288C. Immunological measurements in hepatoma tissue culture cells. The mechanism of action of serum lipoproteins and 25-hydroxycholesterol on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in hepatoma tissue culture (HTC) cells was investigated using antiserum against purified rat liver HMG-CoA reductase (Heller, R. A., and Shrewsbury, M. A. (1976)J. Biol. Chem. 251, 3815-3822). This antiserum cross-reacted with solubilized and membrane-bound HMG-CoA reductase from HTC cells. The enzymes from rat liver and HTC cells appeared antigenically identical. The increase in HMG-CoA reductase activity of HTC cells grown in medium which lacked serum lipoproteins was shown to be due to an increase in immunoprecipitable enzyme. In contrast, the 25-hydroxycholesterol suppression of reductase activity leads to a reduction in the antigenicity of the enzyme rather than a decrease in its number of molecules."}
{"id": "PMID:190222", "title": "Relative importance of 7-methylguanosine in ribosome binding and translation of vesicular stomatitis virus mRNA in wheat germ and reticulocyte cell-free systems.", "content": "Vesicular stomatitis virus mRNAs with these four types of 5'-termini, (a) m7G5'ppp5'(m)Am, (b) ppp5'(m)Am, (c) m7G5'-ppp5' Am, and (d) G5'ppp5'A, were prepared and their translation and ribosome binding analyzed in wheat germ and reticulocyte cell-free protein synthesis systems. The relative efficiencies of translation of individual vesicular stomatitis virus (VSV) mRNAs having type 2 termini ranged from 23 to 29% of the control (type 1) RNA in the reticulocyte system and 6 to 7% of control RNA in the wheat germ system. A similar difference between the two systems was seen in ribosome-binding experiments in which type 2 RNA formed an 80 S initiation complex with high efficiency (70% of control type 1 RNA) in the reticulocyte system, but with low efficiency (17% of control RNA) in the wheat germ system. Similar differences in the importance of m7G in translation in the two systems were seen when VSV mRNAs synthesized in vitro with type 3 and type 4 termini were analyzed. However, the analysis of type 4 RNA (which was synthesized in vitro in the presence of S-adenosylhomocysteine) was complicated by the presence of abnormally large poly(A) at its 3'-end. Another series of experiments showed that compounds such as 5'pm7G and m7G5'ppp5'Np are potent and specific inhibitors of translation of all types of VSV mRNAs in the wheat germ system (greater than 98% inhibition) but cause less than 20% inhibition of translation in the reticulocyte system. Taken together, all of the results indicate that a 5'-terminal m7G is far more important in translation of VSV mRNAs in the heterologous plant cell-free system than in the reticulocyte lysate system.", "contents": "Relative importance of 7-methylguanosine in ribosome binding and translation of vesicular stomatitis virus mRNA in wheat germ and reticulocyte cell-free systems. Vesicular stomatitis virus mRNAs with these four types of 5'-termini, (a) m7G5'ppp5'(m)Am, (b) ppp5'(m)Am, (c) m7G5'-ppp5' Am, and (d) G5'ppp5'A, were prepared and their translation and ribosome binding analyzed in wheat germ and reticulocyte cell-free protein synthesis systems. The relative efficiencies of translation of individual vesicular stomatitis virus (VSV) mRNAs having type 2 termini ranged from 23 to 29% of the control (type 1) RNA in the reticulocyte system and 6 to 7% of control RNA in the wheat germ system. A similar difference between the two systems was seen in ribosome-binding experiments in which type 2 RNA formed an 80 S initiation complex with high efficiency (70% of control type 1 RNA) in the reticulocyte system, but with low efficiency (17% of control RNA) in the wheat germ system. Similar differences in the importance of m7G in translation in the two systems were seen when VSV mRNAs synthesized in vitro with type 3 and type 4 termini were analyzed. However, the analysis of type 4 RNA (which was synthesized in vitro in the presence of S-adenosylhomocysteine) was complicated by the presence of abnormally large poly(A) at its 3'-end. Another series of experiments showed that compounds such as 5'pm7G and m7G5'ppp5'Np are potent and specific inhibitors of translation of all types of VSV mRNAs in the wheat germ system (greater than 98% inhibition) but cause less than 20% inhibition of translation in the reticulocyte system. Taken together, all of the results indicate that a 5'-terminal m7G is far more important in translation of VSV mRNAs in the heterologous plant cell-free system than in the reticulocyte lysate system."}
{"id": "PMID:190223", "title": "Role of apolipoprotein A-I in the structure of human serum high density lipoproteins. Reconstitution studies.", "content": "For a better definition of the role of human serum apolipoprotein A-I (apo A-I) in high density lipoprotein structure, a systematic investigation was carried out on factors influencing the in vitro association of this apoprotein with lipids obtained from the parent high density lipoprotein (HDL); these lipids include phospholipids, free cholesterol, cholesteryl esters, and triglycerides. Following equilibration, mixtures of apo A-I and lipids in varying stoichiometric amounts were fractionated by sequential flotation, CsCl density gradient ultracentrifugation, or gel-permeation chromatography, and the isolated complexes were characterized by physicochemical means. As defined by operational criteria (flotation at density 1,063 to 1.21 g/ml), only two types of HDL complexes were reassembled; one, reconstituted HDLS, small with a radius of 31 A, and the other, reconstituted HDLL, large with a radius of 39 A. The two types incorporated all of the lipid constituents of native HDL and contained 2 and 3 mol of apo A-I, respectively. A maximal yield of reconstituted HDL (R-HDL) was observed at an initial protein concentration of 0.1 muM, where apo A-I is predominantly monomeric. At increasing protein concentrations, the amount of apo A-I recovered in R-HDL was found to be proportional to the initial concentration of monomer and dimer in solution. The composition and yield of the complexes were independent of ionic strength and pH within the ranges studied. Both simple incubation and cosonication of apo A-I with HDL phospholipids produced complexes of identical composition, although the yeild of complexes was higher with co-sonication. When the comparison of the same methods was extended to mixtures of apo A-I and whole HDL lipids, the results confirmed previous observations that co-sonication is essential for the incorporation of the neutral lipid into the R-HDL complexes. The results indicate that (a) in vitro complexation of apo A-I with lipids is under kinetic control; (b) apo A-I can generate a lipid-protein complex with properties similar to those of the parent lipoprotein; (c) the process requires well defined experimental conditions and, most importantly, the presence in solution of monomers and dimers of apo A-I; (d) the number of apo A-I molecules incorporated into R-HDL determines the size and structure of the reassembled particle. All of these observations strongly support the essential role of apo A-I in the structure of human HDL.", "contents": "Role of apolipoprotein A-I in the structure of human serum high density lipoproteins. Reconstitution studies. For a better definition of the role of human serum apolipoprotein A-I (apo A-I) in high density lipoprotein structure, a systematic investigation was carried out on factors influencing the in vitro association of this apoprotein with lipids obtained from the parent high density lipoprotein (HDL); these lipids include phospholipids, free cholesterol, cholesteryl esters, and triglycerides. Following equilibration, mixtures of apo A-I and lipids in varying stoichiometric amounts were fractionated by sequential flotation, CsCl density gradient ultracentrifugation, or gel-permeation chromatography, and the isolated complexes were characterized by physicochemical means. As defined by operational criteria (flotation at density 1,063 to 1.21 g/ml), only two types of HDL complexes were reassembled; one, reconstituted HDLS, small with a radius of 31 A, and the other, reconstituted HDLL, large with a radius of 39 A. The two types incorporated all of the lipid constituents of native HDL and contained 2 and 3 mol of apo A-I, respectively. A maximal yield of reconstituted HDL (R-HDL) was observed at an initial protein concentration of 0.1 muM, where apo A-I is predominantly monomeric. At increasing protein concentrations, the amount of apo A-I recovered in R-HDL was found to be proportional to the initial concentration of monomer and dimer in solution. The composition and yield of the complexes were independent of ionic strength and pH within the ranges studied. Both simple incubation and cosonication of apo A-I with HDL phospholipids produced complexes of identical composition, although the yeild of complexes was higher with co-sonication. When the comparison of the same methods was extended to mixtures of apo A-I and whole HDL lipids, the results confirmed previous observations that co-sonication is essential for the incorporation of the neutral lipid into the R-HDL complexes. The results indicate that (a) in vitro complexation of apo A-I with lipids is under kinetic control; (b) apo A-I can generate a lipid-protein complex with properties similar to those of the parent lipoprotein; (c) the process requires well defined experimental conditions and, most importantly, the presence in solution of monomers and dimers of apo A-I; (d) the number of apo A-I molecules incorporated into R-HDL determines the size and structure of the reassembled particle. All of these observations strongly support the essential role of apo A-I in the structure of human HDL."}
{"id": "PMID:190224", "title": "Adrenal glucocorticoids, adenine nucleotide translocation, and mitochondrial calcium accumulation.", "content": "The administration of dexamethasone to rats markedly diminished the initial rate and maximal extent of substrate-dependent calcium uptake in subsequently isolated liver mitochondria, and enhanced the release of calcium. The apparent Km for calcium transport was not altered by dexamethasone treatment and it ranged from 50 to 80 muM when an EDTA/Ca buffer system was used in the presence of magnesium, and 20 muM when an NTA/Ca buffer system without magnesium was employed. In contrast, when ATP was employed as the energy source, there was no significant difference in initial rate, Km, or the extent of calcium accumulation between mitochondria from control and dexamethasone-treated animals. Although mitochondria from dexamethasone-treated animal showed 15% less cytochrome c oxidase activity/mg of protein, overall respiratory capacity and ATP production from ADP were the same as in control mitochondria. However, mitochondria from dexamethasone-treated animals translocated ATP from inside to outside faster than those from control animals. When the ATP in the medium was depleted by glucose and hexokinase, both types of mitochondria retained essentially all the preloaded calcium until total ATP reached a critical level (7 approximately 5 mumol of ATP/mg of protein). When ATP content fell below this critical level, mitochondria released all the calcium quickly. Dexamethasone treatment increased the susceptibility of mitochondria to the depletion of ATP. These data indicate that the dexamethasone-induced decrease in maximal calcium transport and in calcium retention carrier system per se, but o an altered ability of the mitochondria to regulate intramitochondrial ATP content.", "contents": "Adrenal glucocorticoids, adenine nucleotide translocation, and mitochondrial calcium accumulation. The administration of dexamethasone to rats markedly diminished the initial rate and maximal extent of substrate-dependent calcium uptake in subsequently isolated liver mitochondria, and enhanced the release of calcium. The apparent Km for calcium transport was not altered by dexamethasone treatment and it ranged from 50 to 80 muM when an EDTA/Ca buffer system was used in the presence of magnesium, and 20 muM when an NTA/Ca buffer system without magnesium was employed. In contrast, when ATP was employed as the energy source, there was no significant difference in initial rate, Km, or the extent of calcium accumulation between mitochondria from control and dexamethasone-treated animals. Although mitochondria from dexamethasone-treated animal showed 15% less cytochrome c oxidase activity/mg of protein, overall respiratory capacity and ATP production from ADP were the same as in control mitochondria. However, mitochondria from dexamethasone-treated animals translocated ATP from inside to outside faster than those from control animals. When the ATP in the medium was depleted by glucose and hexokinase, both types of mitochondria retained essentially all the preloaded calcium until total ATP reached a critical level (7 approximately 5 mumol of ATP/mg of protein). When ATP content fell below this critical level, mitochondria released all the calcium quickly. Dexamethasone treatment increased the susceptibility of mitochondria to the depletion of ATP. These data indicate that the dexamethasone-induced decrease in maximal calcium transport and in calcium retention carrier system per se, but o an altered ability of the mitochondria to regulate intramitochondrial ATP content."}
{"id": "PMID:190225", "title": "Direct generation of superoxide anions by flash photolysis of human oxyhemoglobin.", "content": "The results presented in this report suggest that human oxyhemoglobin can directly form methemoglobin and superoxide anion when flashed with low intensity (38 joules) white light. The effect only occurred in quartz but not glass (cut off lambda approximately equal to 300 nm) cuvettes. The formation of O2 was established by observing the reduction of oxidized cytochrome c concomitant with MetHb formation at pH 9, and by showing that superoxide dismultase and catalse inhibit cytochrome c reduction at that pH. The inhibition of cytochrome c reduction by catalase led us to explore the possibility that H2O2 might reduce oxidized cytochrome c at pH 9. We show that H2O2 does reduce oxidized cytochrome c at that pH but not at pH 7. Furthermore, catalase but not superoxide dismutase, almost completely inhibited this reduction process. These experiments serve to confirm our interpretation of the effect of catalase on the reduction of oxidized cytochrome c in the photolytic experiments, thus establishing that H2O2 was also formed. In addition, we were able to identify the production of O2 and H2O2 due to the photolysis of water in agreement with the results of McCord and Fridovich ((1973) Photochem. Photobiol. 17, 115-121). Production of O2 from this source was considerably less than that observed when HbO2 was present. Addition of MetHb to aerated solutions of oxidized cytochrome c did not cause additional reduction, unlike addition of HbO2. The production of MetHb was found to have at least two components. One component was the primary photolytic process, and the second was a strongly pH-dependent reattack of HbO2 by O2. Addition of superoxide dismutase inhibited this second component, but did not significantly effect the primary photolytic process.", "contents": "Direct generation of superoxide anions by flash photolysis of human oxyhemoglobin. The results presented in this report suggest that human oxyhemoglobin can directly form methemoglobin and superoxide anion when flashed with low intensity (38 joules) white light. The effect only occurred in quartz but not glass (cut off lambda approximately equal to 300 nm) cuvettes. The formation of O2 was established by observing the reduction of oxidized cytochrome c concomitant with MetHb formation at pH 9, and by showing that superoxide dismultase and catalse inhibit cytochrome c reduction at that pH. The inhibition of cytochrome c reduction by catalase led us to explore the possibility that H2O2 might reduce oxidized cytochrome c at pH 9. We show that H2O2 does reduce oxidized cytochrome c at that pH but not at pH 7. Furthermore, catalase but not superoxide dismutase, almost completely inhibited this reduction process. These experiments serve to confirm our interpretation of the effect of catalase on the reduction of oxidized cytochrome c in the photolytic experiments, thus establishing that H2O2 was also formed. In addition, we were able to identify the production of O2 and H2O2 due to the photolysis of water in agreement with the results of McCord and Fridovich ((1973) Photochem. Photobiol. 17, 115-121). Production of O2 from this source was considerably less than that observed when HbO2 was present. Addition of MetHb to aerated solutions of oxidized cytochrome c did not cause additional reduction, unlike addition of HbO2. The production of MetHb was found to have at least two components. One component was the primary photolytic process, and the second was a strongly pH-dependent reattack of HbO2 by O2. Addition of superoxide dismutase inhibited this second component, but did not significantly effect the primary photolytic process."}
{"id": "PMID:190226", "title": "Total conversion of glycogen synthase from the I- to the D-form by a cyclic AMP-independent protein kinase from rabbit skeletal muscle.", "content": "A newly discovered cyclic AMP-independent protein kinase, which catalyzes the total conversion of glycogen synthase from the I- to the D-form, has been isolated from rabbit skeletal muscle. This enzyme, designated glycogen synthase kinase, is separable from cyclic AMP-dependent protein kinase by column chromatography on phosphocellulose. Synthase kinase and cyclic AMP-dependent protein kinase are distinct in their specificity for protein substrates, the effects of cyclic AMP and the inhibitor of cyclic AMP-dependent protein kinase on their activities, and the extent to which they phosphorylate I-form glycogen synthase. The phosphorylation of I-form enzyme by synthase kinase results in the incorporation of 4 mol of phosphate/85,000 subunit; however only two of the phosphate sites seem predominantly to determine glucose-6-P dependence. The resulting multiply phosphorylated enzyme, which is highly dependent on glucose-6 P for activity, has a phosphate content comparable to the D-form enzyme isolated from rabbit muscle.", "contents": "Total conversion of glycogen synthase from the I- to the D-form by a cyclic AMP-independent protein kinase from rabbit skeletal muscle. A newly discovered cyclic AMP-independent protein kinase, which catalyzes the total conversion of glycogen synthase from the I- to the D-form, has been isolated from rabbit skeletal muscle. This enzyme, designated glycogen synthase kinase, is separable from cyclic AMP-dependent protein kinase by column chromatography on phosphocellulose. Synthase kinase and cyclic AMP-dependent protein kinase are distinct in their specificity for protein substrates, the effects of cyclic AMP and the inhibitor of cyclic AMP-dependent protein kinase on their activities, and the extent to which they phosphorylate I-form glycogen synthase. The phosphorylation of I-form enzyme by synthase kinase results in the incorporation of 4 mol of phosphate/85,000 subunit; however only two of the phosphate sites seem predominantly to determine glucose-6-P dependence. The resulting multiply phosphorylated enzyme, which is highly dependent on glucose-6 P for activity, has a phosphate content comparable to the D-form enzyme isolated from rabbit muscle."}
{"id": "PMID:190227", "title": "Expression of genes for metabolism of cyclic adenosine 3':5'-monophosphate in somatic cells. beta-Adrenergic and PGE1 receptors in parental and hybrid cells.", "content": "Using the ligands [125I]iodohydroxybenzylpindolol and [3H]prostaglandin E1 ([3H]PGE1), we have studied the relationship of receptors for beta-adrenergic agents and for PGE1 to adenylate cyclase in membranes of parental, hybrid, and variant mammalian cell lines. Fusion of parental clones responsive to beta-adrenergic agonists (beta+) with unresponsive clones (beta-) produced hybrid clones with a greatly diminished beta-adrenergic response; beta+ X beta leads to beta-. Binding studies with [125I]iodohydroxybenzylpindolol showed a decreased concentration of beta receptors in six such hybrid clones. Thus, paucity of beta-adrenergic receptors is probably a sufficient, albeit not necessarily complete, explanation for the decreased beta-adrenergic responsiveness of the hybrid clones. When a clone with beta receptor but without apparent adenylate cyclase activity (HC-1) was hybridized with a beta- clone that has adenylate cyclase (B82), a responsive hybrid clone was obtained. In nine cell hybrids produced by the fusion of clones responsive (PGE1+) and unresponsive (PGE1-) to PGE1, high affinity binding sites for [3H]PGE1 were expressed in the same manner as was PGE1-sensitive adenylate cyclase: PGE1+ X PGE1 leads to PGE1+. The chemical specificities and affinities of the parental receptors and responsive adenylate cyclases were faithfully reproduced in the hybrid clones. Activation by PGE1 was proportional to the occupation of the high affinity receptors. In a wild type lymphoma clone (24.3.2), the concentration dependences for binding of [3H]PGE1 and for activation of adenyalte cyclase by PGE1 were identical. In a variant lymphoma clone (94.15.1) lacking adenylate cyclase activity, no high affinity receptors for PGE1 were detected, whereas beta-adrenergic receptors have been demonstrated in this variant clone (Insel, P.A., Maguire, M.E., Gilman, A.G., Coffino, P., Bourne, H., and Melmon, K. (1976) Mol. Pharmacol. 12, 1062-1069). Hybrid cells formed by the fusion of 94.15.1 with cell line RAG (PGE1-) responded to PGE1. Clone 94.15.1 may have receptors for PGE1 of reduced affinity or in low concentration. Alternatively, RAG and 94.15.1 may have complementary genetic defects such that the RAG X 94.15.1 hybrid cells express a hormonally responsive receptor-adenylate cyclase system.", "contents": "Expression of genes for metabolism of cyclic adenosine 3':5'-monophosphate in somatic cells. beta-Adrenergic and PGE1 receptors in parental and hybrid cells. Using the ligands [125I]iodohydroxybenzylpindolol and [3H]prostaglandin E1 ([3H]PGE1), we have studied the relationship of receptors for beta-adrenergic agents and for PGE1 to adenylate cyclase in membranes of parental, hybrid, and variant mammalian cell lines. Fusion of parental clones responsive to beta-adrenergic agonists (beta+) with unresponsive clones (beta-) produced hybrid clones with a greatly diminished beta-adrenergic response; beta+ X beta leads to beta-. Binding studies with [125I]iodohydroxybenzylpindolol showed a decreased concentration of beta receptors in six such hybrid clones. Thus, paucity of beta-adrenergic receptors is probably a sufficient, albeit not necessarily complete, explanation for the decreased beta-adrenergic responsiveness of the hybrid clones. When a clone with beta receptor but without apparent adenylate cyclase activity (HC-1) was hybridized with a beta- clone that has adenylate cyclase (B82), a responsive hybrid clone was obtained. In nine cell hybrids produced by the fusion of clones responsive (PGE1+) and unresponsive (PGE1-) to PGE1, high affinity binding sites for [3H]PGE1 were expressed in the same manner as was PGE1-sensitive adenylate cyclase: PGE1+ X PGE1 leads to PGE1+. The chemical specificities and affinities of the parental receptors and responsive adenylate cyclases were faithfully reproduced in the hybrid clones. Activation by PGE1 was proportional to the occupation of the high affinity receptors. In a wild type lymphoma clone (24.3.2), the concentration dependences for binding of [3H]PGE1 and for activation of adenyalte cyclase by PGE1 were identical. In a variant lymphoma clone (94.15.1) lacking adenylate cyclase activity, no high affinity receptors for PGE1 were detected, whereas beta-adrenergic receptors have been demonstrated in this variant clone (Insel, P.A., Maguire, M.E., Gilman, A.G., Coffino, P., Bourne, H., and Melmon, K. (1976) Mol. Pharmacol. 12, 1062-1069). Hybrid cells formed by the fusion of 94.15.1 with cell line RAG (PGE1-) responded to PGE1. Clone 94.15.1 may have receptors for PGE1 of reduced affinity or in low concentration. Alternatively, RAG and 94.15.1 may have complementary genetic defects such that the RAG X 94.15.1 hybrid cells express a hormonally responsive receptor-adenylate cyclase system."}
{"id": "PMID:190228", "title": "Serum angiotensin-converting enzyme. Isolation and relationship to the pulmonary enzyme.", "content": "Angiotensin-converting enzyme from rabbit serum was purified almost 60,000-fold to apparent homogeneity by a procedure exploiting its affinity for antibodies prepared against the enzyme from lung. The pure serum and pulmonary enzymes exhibited identical behavior during gel filtration, sucrose gradient centrifugation, and disc gel electrophoresis in the reduced, denatured state. Their catalytic properties with hippurylhistidylleucine, angiotensin I, and bradykinin as substrates were similar and their reactivity with antilung enzyme antibody was indistinguishable as examined by immunodiffusion, inhibition dose-response curves, and radioimmunoassay. Their content of fucose, mannose, galactose, and N-acetylglucosamine was also comparable; however, N-acetylneuraminic acid was much more abundant in the serum glycoprotein. This difference may reflect selective removal of sialic acid-deficient enzyme molecules from the circulation by the hepatic lectin which has been postulated to initiate the catabolic phase for plasma glycoproteins (Ashwell, G., and Morell, A.G. (1974) Adv. Enzymol. Relat. Areas Mol. Biol. 41, 91-128).", "contents": "Serum angiotensin-converting enzyme. Isolation and relationship to the pulmonary enzyme. Angiotensin-converting enzyme from rabbit serum was purified almost 60,000-fold to apparent homogeneity by a procedure exploiting its affinity for antibodies prepared against the enzyme from lung. The pure serum and pulmonary enzymes exhibited identical behavior during gel filtration, sucrose gradient centrifugation, and disc gel electrophoresis in the reduced, denatured state. Their catalytic properties with hippurylhistidylleucine, angiotensin I, and bradykinin as substrates were similar and their reactivity with antilung enzyme antibody was indistinguishable as examined by immunodiffusion, inhibition dose-response curves, and radioimmunoassay. Their content of fucose, mannose, galactose, and N-acetylglucosamine was also comparable; however, N-acetylneuraminic acid was much more abundant in the serum glycoprotein. This difference may reflect selective removal of sialic acid-deficient enzyme molecules from the circulation by the hepatic lectin which has been postulated to initiate the catabolic phase for plasma glycoproteins (Ashwell, G., and Morell, A.G. (1974) Adv. Enzymol. Relat. Areas Mol. Biol. 41, 91-128)."}
{"id": "PMID:190229", "title": "Electron paramagnetic resonance study of carp methemoglobin.", "content": "The g anisotropy of the EPR spectra of carp azidomethemoglobin is found to be pH-dependent, whereas, the spectra of human azidomethemoglobin are not. The two hemoglobins have the same g values at alkaline pH values. Crystal field analysis yielded values of 2.25 and 3.31, respectively, for the rhombic distortion, V/lambda, and the tetragonal distortion, delta/lambda. The spin orbit coupling constant is lambda. At pH 4.0 the values of V/lambda and delta/lambda for carp azidomethemoglobin became 1.95 and 4.76, respectively, whereas those for the human hemoglobin are virtually unchanged. The results are interpreted to mean an increase of out-ofplane displacement of the iron atom and stabilization of the T form of carp azidomethemoglobin by high proton concentration. At pH 6.0 and lower, the EPR spectra of carp azidomethemoglobin showed the presence of about 1.5% of high spin species, the amount is not affected by excess of either inositol hexaphosphate or sodium azide. The EPR spectra of aquo- and fluoroderivatives of carp methemoglobin were not affected by pH changes.", "contents": "Electron paramagnetic resonance study of carp methemoglobin. The g anisotropy of the EPR spectra of carp azidomethemoglobin is found to be pH-dependent, whereas, the spectra of human azidomethemoglobin are not. The two hemoglobins have the same g values at alkaline pH values. Crystal field analysis yielded values of 2.25 and 3.31, respectively, for the rhombic distortion, V/lambda, and the tetragonal distortion, delta/lambda. The spin orbit coupling constant is lambda. At pH 4.0 the values of V/lambda and delta/lambda for carp azidomethemoglobin became 1.95 and 4.76, respectively, whereas those for the human hemoglobin are virtually unchanged. The results are interpreted to mean an increase of out-ofplane displacement of the iron atom and stabilization of the T form of carp azidomethemoglobin by high proton concentration. At pH 6.0 and lower, the EPR spectra of carp azidomethemoglobin showed the presence of about 1.5% of high spin species, the amount is not affected by excess of either inositol hexaphosphate or sodium azide. The EPR spectra of aquo- and fluoroderivatives of carp methemoglobin were not affected by pH changes."}
{"id": "PMID:190230", "title": "Nonequivalence of subunits in [15N]nitrosylhemoglobin Kansas. A single crystal electron paramagnetic resonance investigation.", "content": "EPR spectra of Hb15NO crystals of mutant Kansas (Asn G4(102) beta leads to Thr) have been recorded at every 5' intervals and in three orthogonal planes. The nitrosylhemes are nonequivalent for the alpha and beta subunits, their assignments are made possible by comparison with the powder EPR specrtra of Hb15NO of mutant Iwate (His F8(87)alpha leads to Tyr) (Trittelvitz, E., Gersonde, K., and Winterhalter, K.H. (1975) Eur. J. Biochem. 51, 33-42). The EPR parameters for the beta-nitrosylhemes of Hb Kansas are: gxx=2.094 gyy=2.031, gzz=2.00, Azetazeta=11 G, Azetazeta=32.5 G, Aetaeta=12.5 G; the Fe-N-O bond angle is about 105 degrees. The paramters for the alpha-nitrosyl hemes are: gxx=2.058, gyy=2.021, gzz=1.977, Azetazeta=24.5 G, Azetazeta less than or equal to 5G, Aetaeta=23 G; the Fe-N-O bond angle is about 167 degrees. Hyperfine splittings of 7 to 8 gauss with 14Nepsilon atom of His(F8) were observed for the beta-nitrosylhemes; none was resolved for the alpha-nitrosylhemes. The results were interpreted to mean that the tension on the iron of the beta subunits is not large in the unliganded state and this tension was not greatly increased by the binding of nitric oxide in the strongly bent configuration. The tension at the iron in the deoxyhemoglobin is dominant at the alpha subunits. Binding of nitric oxide in this case causing either the breaking or great weakening of the Fe-His(F8) bond. The nitrosyl is in a nearly linear configuration. The unpaired electron densities at the nitrogen atom of the bound nitric oxide is about 63% for the beta-nitrosylheme and 37% for the alpha-nitrosylhemes.", "contents": "Nonequivalence of subunits in [15N]nitrosylhemoglobin Kansas. A single crystal electron paramagnetic resonance investigation. EPR spectra of Hb15NO crystals of mutant Kansas (Asn G4(102) beta leads to Thr) have been recorded at every 5' intervals and in three orthogonal planes. The nitrosylhemes are nonequivalent for the alpha and beta subunits, their assignments are made possible by comparison with the powder EPR specrtra of Hb15NO of mutant Iwate (His F8(87)alpha leads to Tyr) (Trittelvitz, E., Gersonde, K., and Winterhalter, K.H. (1975) Eur. J. Biochem. 51, 33-42). The EPR parameters for the beta-nitrosylhemes of Hb Kansas are: gxx=2.094 gyy=2.031, gzz=2.00, Azetazeta=11 G, Azetazeta=32.5 G, Aetaeta=12.5 G; the Fe-N-O bond angle is about 105 degrees. The paramters for the alpha-nitrosyl hemes are: gxx=2.058, gyy=2.021, gzz=1.977, Azetazeta=24.5 G, Azetazeta less than or equal to 5G, Aetaeta=23 G; the Fe-N-O bond angle is about 167 degrees. Hyperfine splittings of 7 to 8 gauss with 14Nepsilon atom of His(F8) were observed for the beta-nitrosylhemes; none was resolved for the alpha-nitrosylhemes. The results were interpreted to mean that the tension on the iron of the beta subunits is not large in the unliganded state and this tension was not greatly increased by the binding of nitric oxide in the strongly bent configuration. The tension at the iron in the deoxyhemoglobin is dominant at the alpha subunits. Binding of nitric oxide in this case causing either the breaking or great weakening of the Fe-His(F8) bond. The nitrosyl is in a nearly linear configuration. The unpaired electron densities at the nitrogen atom of the bound nitric oxide is about 63% for the beta-nitrosylheme and 37% for the alpha-nitrosylhemes."}
{"id": "PMID:190231", "title": "Formation of a biologically active, ordered complex from two overlapping fragments of cytochrome c.", "content": "A noncovalent complex of the apoprotein (1-104) and cyanogen bromide heme fragment containing residues 1 to 65, (1-65) H, has been prepared from horse heart cytochrome c. Conditions under which the redundant portions of the ferrous complex can be removed by limited trypsin digestion have been devised. The complementing fragments have been isolated from the derived complexes and four apofragments and one heme fragment have been identified in the amino acid sequence of cytochrome c. They are (39-104), (40-104), (54-104), (56-104), and (1-53)H. The formation of an ordered ferric complex composed of one heme fragment and one apofragment for the cases (1-53)H (39-104), (1-53)H-(40-104), (1-53)H-(54-104), and (1-53)H-(56-104) has been demonstrated by the quenching of the tryptophan 59 fluorescence and the regain of biological activity in a cytochrome b2 assay. The apparent dissociation constant has been estimated as less than 3 X 10(-7) M in all the aforementioned cases. Thus, the region (between residues 38 and 57) of the amino acid sequence permissible for cleavage without disruption of the ordered structure indicated by the present in vitro experiments corresponds to that (between residues 38 and 57) evolutionally deleted in the three-dimensional structure of Pseudomonas aeruginosa cytochrome c551 discovered by Dickerson et al. (Dickerson, R.E., Timkovich, R., and Almassy, R.J. (1976) J. Mol. Biol. 100, 473-491).", "contents": "Formation of a biologically active, ordered complex from two overlapping fragments of cytochrome c. A noncovalent complex of the apoprotein (1-104) and cyanogen bromide heme fragment containing residues 1 to 65, (1-65) H, has been prepared from horse heart cytochrome c. Conditions under which the redundant portions of the ferrous complex can be removed by limited trypsin digestion have been devised. The complementing fragments have been isolated from the derived complexes and four apofragments and one heme fragment have been identified in the amino acid sequence of cytochrome c. They are (39-104), (40-104), (54-104), (56-104), and (1-53)H. The formation of an ordered ferric complex composed of one heme fragment and one apofragment for the cases (1-53)H (39-104), (1-53)H-(40-104), (1-53)H-(54-104), and (1-53)H-(56-104) has been demonstrated by the quenching of the tryptophan 59 fluorescence and the regain of biological activity in a cytochrome b2 assay. The apparent dissociation constant has been estimated as less than 3 X 10(-7) M in all the aforementioned cases. Thus, the region (between residues 38 and 57) of the amino acid sequence permissible for cleavage without disruption of the ordered structure indicated by the present in vitro experiments corresponds to that (between residues 38 and 57) evolutionally deleted in the three-dimensional structure of Pseudomonas aeruginosa cytochrome c551 discovered by Dickerson et al. (Dickerson, R.E., Timkovich, R., and Almassy, R.J. (1976) J. Mol. Biol. 100, 473-491)."}
{"id": "PMID:190232", "title": "Inactivation of avian myeloblastosis virus DNA polymerase by specific binding of pyridoxal 5'-phosphate to deoxynucleoside triphosphate binding site.", "content": "Avian myeloblastosis virus (AMV) DNA polymerase is inactivated by preincubation with pyridoxal 5'-phosphate. This inactivation is relatively specific since various pyridoxal-5'-P analogs cause no inactivation. This effect is reversible but can be made irreversible by reduction with sodium borohydride; the reduced pyridoxal-5'-P adduct exhibits a new absorbance maximum at 325 nm and a fluorescence emission at 392 nm when excited at 325 nm. The evidence presented suggests the formation of a Schiff base between pyridoxal-5'-P and a nucleophilic residue of AMV DNA polymerase. The presence of a deoxynucleoside 5'-triphosphate (dTTP) protected the enzyme from inactivation. Reduction of the pyridoxal-5'-P enzyme complex in the presence or absence of a deoxynucleoside 5'-triphosphate showed that the alpha subunit possesses five reactive amino groups, one of which is essential for catalytic activity; the beta subunit has three reactive amino groups which are not involved in the deoxynucleoside binding site.", "contents": "Inactivation of avian myeloblastosis virus DNA polymerase by specific binding of pyridoxal 5'-phosphate to deoxynucleoside triphosphate binding site. Avian myeloblastosis virus (AMV) DNA polymerase is inactivated by preincubation with pyridoxal 5'-phosphate. This inactivation is relatively specific since various pyridoxal-5'-P analogs cause no inactivation. This effect is reversible but can be made irreversible by reduction with sodium borohydride; the reduced pyridoxal-5'-P adduct exhibits a new absorbance maximum at 325 nm and a fluorescence emission at 392 nm when excited at 325 nm. The evidence presented suggests the formation of a Schiff base between pyridoxal-5'-P and a nucleophilic residue of AMV DNA polymerase. The presence of a deoxynucleoside 5'-triphosphate (dTTP) protected the enzyme from inactivation. Reduction of the pyridoxal-5'-P enzyme complex in the presence or absence of a deoxynucleoside 5'-triphosphate showed that the alpha subunit possesses five reactive amino groups, one of which is essential for catalytic activity; the beta subunit has three reactive amino groups which are not involved in the deoxynucleoside binding site."}
{"id": "PMID:190233", "title": "Concentrations of cyclic AMP-dependent protein kinase subunits in various tissues.", "content": "The concentrations of the regulatory (R) and catalytic (C) subunits of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase(s) were measured in extracts of skeletal muscle, heart, liver, kidney, and brain. These concentrations were also estimated for the particulate fraction from brain, the only tissue in which a major part of the total activity was not readily extracted in a soluble form. Values for R were determined by measuring the amount of cyclic [3H]amp bound to protein in these tissue fractions under specified conditions; it was assumed that 1 mol of cyclic AMP binds to 1 mol of R. Values for C were determined from measurements of the specific protein kinase activity of the fractions utilizing the turnover number of pure C in the calculations. Turnover numbers for C were found to be identical for this subunit obtained in the pure form from rabbit skeletal muscle, rabbit liver, and beef heart. The methods used for measuring C were evaluated by kinetic studies and through the use of the specific heatstable protein inhibitor of cyclic AMP-dependent protein kinase(s). R and C were found to exist in a 1:1 molar ratio in all of the tissue fractions that were studied. the absolute concentrations of R and C ranged from 0.23 mumol/kg wet weight for liver to 0.78 mumol/kg wet weight for brain. For brain this value was based on the amount of each subunit in the particulate as well as the soluble fraction. For other tissues the values were based solely on the subunit content of the latter fraction. It was noted that the molar concentrations of R are close to those of cyclic AMP under basal conditions in the various tissues.", "contents": "Concentrations of cyclic AMP-dependent protein kinase subunits in various tissues. The concentrations of the regulatory (R) and catalytic (C) subunits of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase(s) were measured in extracts of skeletal muscle, heart, liver, kidney, and brain. These concentrations were also estimated for the particulate fraction from brain, the only tissue in which a major part of the total activity was not readily extracted in a soluble form. Values for R were determined by measuring the amount of cyclic [3H]amp bound to protein in these tissue fractions under specified conditions; it was assumed that 1 mol of cyclic AMP binds to 1 mol of R. Values for C were determined from measurements of the specific protein kinase activity of the fractions utilizing the turnover number of pure C in the calculations. Turnover numbers for C were found to be identical for this subunit obtained in the pure form from rabbit skeletal muscle, rabbit liver, and beef heart. The methods used for measuring C were evaluated by kinetic studies and through the use of the specific heatstable protein inhibitor of cyclic AMP-dependent protein kinase(s). R and C were found to exist in a 1:1 molar ratio in all of the tissue fractions that were studied. the absolute concentrations of R and C ranged from 0.23 mumol/kg wet weight for liver to 0.78 mumol/kg wet weight for brain. For brain this value was based on the amount of each subunit in the particulate as well as the soluble fraction. For other tissues the values were based solely on the subunit content of the latter fraction. It was noted that the molar concentrations of R are close to those of cyclic AMP under basal conditions in the various tissues."}
{"id": "PMID:190234", "title": "Regulation of cyclic nucleotide phosphodiesterases in cultured hepatoma cells by dexamethasone and N6,O2'-dibutyryl adenosine 3':k'-monophosphate.", "content": "DEAE-Bio-Gel chromatography of 100,000 X g supernatant from cultured HTC hepatoma cells separated cyclic nucleotide phosphodiesterase into three forms, numbered E I, E II, and E III in order of elution from the column, E I had a low Km for cyclic guanosine 3':5'-monophosphate (cGMP) and a high Km for cyclic adenosine 3':5'-monophosphate (cAMP), E II exhibited anomalous kinetics. At low substrate concentrations (0.5 muM) cGMP was hydrolyzed more rapidly than cAMP and hydrolysis of 0.5 muM cAMP was stimulated by 1 muM cGMP. E III had a low Km for cAMP. Incubation of cells with 1 muM dexamethasone for 72 h decreased the activity of E I and E II. In cells incubated with N6,O2'-dibutyryl cAMP plus 3-isobutyl-1-methylxanthine for 14 h the activity of E III was increased approximately 100%. Similar activities of calcium-dependent, heat stable phosphodiesterase activator were recovered from supernatants from all cells. These studies have established the presence, in a homogeneous population of hepatoma cells, of at least three forms of cyclic nucleotide phosphodiesterase, the activities of which can be independently regulated.", "contents": "Regulation of cyclic nucleotide phosphodiesterases in cultured hepatoma cells by dexamethasone and N6,O2'-dibutyryl adenosine 3':k'-monophosphate. DEAE-Bio-Gel chromatography of 100,000 X g supernatant from cultured HTC hepatoma cells separated cyclic nucleotide phosphodiesterase into three forms, numbered E I, E II, and E III in order of elution from the column, E I had a low Km for cyclic guanosine 3':5'-monophosphate (cGMP) and a high Km for cyclic adenosine 3':5'-monophosphate (cAMP), E II exhibited anomalous kinetics. At low substrate concentrations (0.5 muM) cGMP was hydrolyzed more rapidly than cAMP and hydrolysis of 0.5 muM cAMP was stimulated by 1 muM cGMP. E III had a low Km for cAMP. Incubation of cells with 1 muM dexamethasone for 72 h decreased the activity of E I and E II. In cells incubated with N6,O2'-dibutyryl cAMP plus 3-isobutyl-1-methylxanthine for 14 h the activity of E III was increased approximately 100%. Similar activities of calcium-dependent, heat stable phosphodiesterase activator were recovered from supernatants from all cells. These studies have established the presence, in a homogeneous population of hepatoma cells, of at least three forms of cyclic nucleotide phosphodiesterase, the activities of which can be independently regulated."}
{"id": "PMID:190235", "title": "Role of phosphoprotein phosphatases in reversible deactivation of chicken adipose tissue hormone-sensitive lipase.", "content": "The reversible deactivation of chicken adipose tissue hormone-sensitive lipase alpha(previously activated with Mg2+ ATP and adenosine 3':5'-monophosphate) required Mg2+ and was inhibited by phosphate. These results are consistent with the assumption that deactivation of the protein kinase-activated enzyme is catalyzed by a lipase phosphatase. Cholesterol ester is catalyzed by a lipase phosphatase. Cholesterol ester hydrolase similarly was activated and reversibly deactivated. The activity of endogenous lipase phosphatase in pH 5.2 precipitate fractions was reduced, and in some cases eliminated, by incubation at 50 degrees for 20 min in buffer containing 20% glycerol. Heating at 50 degrees greatly increased the apparent percentage activation of triglyceride and cholesterol ester hydrolases but this was due to a selective decrease in basal (nonactivated) hydrolase activities. Essentially all endogenous lipase phosphatase could be removed by treatment of the pH 5.2 precipitate fraction with ATP-Sepharose affinity gel. The addition of a partially purified preparation of rat liver phosphorylase phosphatase deactivated triglyceride and cholesterol ester hydrolases. The deactivation process was concentration, 5 mM) and was inhibited by 5 mM phosphate and by phosphorylase alpha. Reversible deactivation of hormone-sensitive lipase alpha was also observed with crude prepa- and by phosphorylase alpha. Reversible deactivation of hormone-sensitive lipas alpha was also observed with crude preparations of phosphoprotein phosphatases from rat  and turkey hearts, and from rat epididymal fat pads. Thus, hormone-sensitive lipase is deactivated by a variety of phosphoprotein phosphatases from different tissues and different species, implying a low degree of specificity for the deactivating system.", "contents": "Role of phosphoprotein phosphatases in reversible deactivation of chicken adipose tissue hormone-sensitive lipase. The reversible deactivation of chicken adipose tissue hormone-sensitive lipase alpha(previously activated with Mg2+ ATP and adenosine 3':5'-monophosphate) required Mg2+ and was inhibited by phosphate. These results are consistent with the assumption that deactivation of the protein kinase-activated enzyme is catalyzed by a lipase phosphatase. Cholesterol ester is catalyzed by a lipase phosphatase. Cholesterol ester hydrolase similarly was activated and reversibly deactivated. The activity of endogenous lipase phosphatase in pH 5.2 precipitate fractions was reduced, and in some cases eliminated, by incubation at 50 degrees for 20 min in buffer containing 20% glycerol. Heating at 50 degrees greatly increased the apparent percentage activation of triglyceride and cholesterol ester hydrolases but this was due to a selective decrease in basal (nonactivated) hydrolase activities. Essentially all endogenous lipase phosphatase could be removed by treatment of the pH 5.2 precipitate fraction with ATP-Sepharose affinity gel. The addition of a partially purified preparation of rat liver phosphorylase phosphatase deactivated triglyceride and cholesterol ester hydrolases. The deactivation process was concentration, 5 mM) and was inhibited by 5 mM phosphate and by phosphorylase alpha. Reversible deactivation of hormone-sensitive lipase alpha was also observed with crude prepa- and by phosphorylase alpha. Reversible deactivation of hormone-sensitive lipas alpha was also observed with crude preparations of phosphoprotein phosphatases from rat  and turkey hearts, and from rat epididymal fat pads. Thus, hormone-sensitive lipase is deactivated by a variety of phosphoprotein phosphatases from different tissues and different species, implying a low degree of specificity for the deactivating system."}
{"id": "PMID:190236", "title": "Artificial hybrid protein containing a toxic protein fragment and a cell membrane receptor-binding moiety in a disulfide conjugate. I. Synthesis of diphtheria toxin fragment A-S-S-human placental lactogen with methyl-5-bromovalerimidate.", "content": "In order to study the mechanism of entry of plant seed and bacterial toxins into mammalian cells, methods have been developed to synthesize artificial protein hybrid conjugates containing a moiety which binds to a cell membrane receptor and an active fragment of a toxin protein. Utilizing methyl-5-bromovalerimidate, a disulfide cross-linked conjugate of human placental lactogen (hPL) and diphtheria toxin fragment A (toxin A) was synthesized. The reagent was prepared from 5-bromovaleryl nitrile by Pinner synthesis and then used to amidinate hPL. The bromo group thus introduced was converted to S-sulfonate by nucleophilic displacement with 1 M aqueous sodium thiosulfate at room temperature overnight. The S-sulfonated hPL reacted readily with the-SH gorup of reduced toxin A to form a 1 mol/mol of disulfide conjugate in high yield. Thus when reduced toxin A was incubated with a 4-fold excess of the hPL S-sulfonate at 4 degrees and pH 6.5 for 120 h, a conjugate yield of 50% relative to the toxin A input was obtained. Homopolymer formation was negligible and the product was purified by gel filtration on Sephadex G-150. Purity of the conjugate estimated by quantitative analysis of sodium dodecyl sulfate gels was 90%. The toxin A-hPL conjugate retained the activities of both toxin A and hPL, as reported in the accompanying paper. This method of preparing protein hybrid conjugates appeared to have advantages over previous methods utilizing bifunctional reagents with respect to both yield and freedom from homopolymer formation.", "contents": "Artificial hybrid protein containing a toxic protein fragment and a cell membrane receptor-binding moiety in a disulfide conjugate. I. Synthesis of diphtheria toxin fragment A-S-S-human placental lactogen with methyl-5-bromovalerimidate. In order to study the mechanism of entry of plant seed and bacterial toxins into mammalian cells, methods have been developed to synthesize artificial protein hybrid conjugates containing a moiety which binds to a cell membrane receptor and an active fragment of a toxin protein. Utilizing methyl-5-bromovalerimidate, a disulfide cross-linked conjugate of human placental lactogen (hPL) and diphtheria toxin fragment A (toxin A) was synthesized. The reagent was prepared from 5-bromovaleryl nitrile by Pinner synthesis and then used to amidinate hPL. The bromo group thus introduced was converted to S-sulfonate by nucleophilic displacement with 1 M aqueous sodium thiosulfate at room temperature overnight. The S-sulfonated hPL reacted readily with the-SH gorup of reduced toxin A to form a 1 mol/mol of disulfide conjugate in high yield. Thus when reduced toxin A was incubated with a 4-fold excess of the hPL S-sulfonate at 4 degrees and pH 6.5 for 120 h, a conjugate yield of 50% relative to the toxin A input was obtained. Homopolymer formation was negligible and the product was purified by gel filtration on Sephadex G-150. Purity of the conjugate estimated by quantitative analysis of sodium dodecyl sulfate gels was 90%. The toxin A-hPL conjugate retained the activities of both toxin A and hPL, as reported in the accompanying paper. This method of preparing protein hybrid conjugates appeared to have advantages over previous methods utilizing bifunctional reagents with respect to both yield and freedom from homopolymer formation."}
{"id": "PMID:190237", "title": "Artificial hybrid protein containing a toxic protein fragment and a cell membrane receptor-binding moiety in a disulfide conjugate. II. Biochemical and biologic properties of diphtheria toxin fragment A-S-S-human placental lactogen.", "content": "The biochemical and biologic properties of a purified disulfide conjugate of diphtheria toxin fragment A and human placental lactogen (toxin A-hPL) have been studied by (a) assaying the ADP-ribosyltransferase activity of the intact conjugate, (b) assaying the binding of the intact conjugate to mammary gland plasma membrane lactogenic receptors, and (c) assaying the effect of the conjugate on the rate of protein synthesis in rabbit mammary gland explants maintained in organ culture. The toxin A-hPL conjugate retains one-third of the NAD+:EF-2 ADP-ribosyltransferase activity of toxin A, and 26% of the hPL-binding activity to lactogenic receptors. Binding activity was demonstrated by radioreceptor assay and by assaying toxin A activity bound to membranes which was competitively displaced by excess hPL. Since the toxin A-hPL conjugate retained activities of its separate subunits, it could be regarded as a structural analogue of nicked diphtheria toxin with replacement of the original membrane-binding chain by another binding chain that is specific for lactogenic receptor. However, the conjugate failed to inhibit protein synthesis in organ-cultured mammary gland explants, although these were sensitive to native diphtheria toxin and could bind hPL. It is concluded from these results that the toxin A-hPL conjugate does not act as a functional analogue of diphtheria toxin with altered receptor specificity, and that the hPL receptor cannot mediate the entry of toxin A or toxin A-hPL from membrane-bound conjugate into the cytosol site of action of toxin A.", "contents": "Artificial hybrid protein containing a toxic protein fragment and a cell membrane receptor-binding moiety in a disulfide conjugate. II. Biochemical and biologic properties of diphtheria toxin fragment A-S-S-human placental lactogen. The biochemical and biologic properties of a purified disulfide conjugate of diphtheria toxin fragment A and human placental lactogen (toxin A-hPL) have been studied by (a) assaying the ADP-ribosyltransferase activity of the intact conjugate, (b) assaying the binding of the intact conjugate to mammary gland plasma membrane lactogenic receptors, and (c) assaying the effect of the conjugate on the rate of protein synthesis in rabbit mammary gland explants maintained in organ culture. The toxin A-hPL conjugate retains one-third of the NAD+:EF-2 ADP-ribosyltransferase activity of toxin A, and 26% of the hPL-binding activity to lactogenic receptors. Binding activity was demonstrated by radioreceptor assay and by assaying toxin A activity bound to membranes which was competitively displaced by excess hPL. Since the toxin A-hPL conjugate retained activities of its separate subunits, it could be regarded as a structural analogue of nicked diphtheria toxin with replacement of the original membrane-binding chain by another binding chain that is specific for lactogenic receptor. However, the conjugate failed to inhibit protein synthesis in organ-cultured mammary gland explants, although these were sensitive to native diphtheria toxin and could bind hPL. It is concluded from these results that the toxin A-hPL conjugate does not act as a functional analogue of diphtheria toxin with altered receptor specificity, and that the hPL receptor cannot mediate the entry of toxin A or toxin A-hPL from membrane-bound conjugate into the cytosol site of action of toxin A."}
{"id": "PMID:190238", "title": "Progesterone-stimulated meiotic cell division in Xenopus oocytes. Induction by regulatory subunit and inhibition by catalytic subunit of adenosine 3':5'-monophosphate-dependent protein kinase.", "content": "Ripe Xenopus oocytes in first meiotic prophase when incubated with progesterone in vitro progress synchronously in 3 to 5 h without interphase to second meiotic metaphase where they remain until fertilization or activation. Using highly purified preparations of regulatory and catalytic subunits of adenosine 3':5'-monophosphate-dependent protein kinase from muscle, this progesterone-stimulated cell division sequence was found to be inhibited by microinjection of the catalytic subunit and induced directly in the absence of progesterone after microinjection of regulatory subunit. Dose-response curves revealed that half-maximal effects of regulatory and catalytic subunits occurred at an internal concentration of approximately 0.1 muM. These results indicate that the catalytic subunit is necessary and sufficient to block progesterone-stimulated meiotic cell division. Other experiments revealed that the catalytic subunit was inhibitory only during the first hour after progesterone exposure, suggesting that initial steps in meiotic cell division are affected. Control experiments demonstrate that the muscle cAMP-dependent protein kinase subunits may interact with the endogenous oocyte protein kinase. The results support a model in which meiotic cell division is regulated by a phosphoprotein subject to control by cAMP-dependent protein kinase.", "contents": "Progesterone-stimulated meiotic cell division in Xenopus oocytes. Induction by regulatory subunit and inhibition by catalytic subunit of adenosine 3':5'-monophosphate-dependent protein kinase. Ripe Xenopus oocytes in first meiotic prophase when incubated with progesterone in vitro progress synchronously in 3 to 5 h without interphase to second meiotic metaphase where they remain until fertilization or activation. Using highly purified preparations of regulatory and catalytic subunits of adenosine 3':5'-monophosphate-dependent protein kinase from muscle, this progesterone-stimulated cell division sequence was found to be inhibited by microinjection of the catalytic subunit and induced directly in the absence of progesterone after microinjection of regulatory subunit. Dose-response curves revealed that half-maximal effects of regulatory and catalytic subunits occurred at an internal concentration of approximately 0.1 muM. These results indicate that the catalytic subunit is necessary and sufficient to block progesterone-stimulated meiotic cell division. Other experiments revealed that the catalytic subunit was inhibitory only during the first hour after progesterone exposure, suggesting that initial steps in meiotic cell division are affected. Control experiments demonstrate that the muscle cAMP-dependent protein kinase subunits may interact with the endogenous oocyte protein kinase. The results support a model in which meiotic cell division is regulated by a phosphoprotein subject to control by cAMP-dependent protein kinase."}
{"id": "PMID:190239", "title": "Turbidimetric ultracentrifugation. Application to the study of human serum very low density lipoprotein distributions.", "content": "In this communication it is shown that the sedimentation coefficient distribution may be accurately measured for very large particles using turbidimetric techniques and the ultraviolet-scanning analytical ultracentrifuge. A principal advantage is that turbidity is a function of the product of concentration and molecular weight; thus, large particles may be observed even when present in very small amounts. We propose to call this method of analysis \"turbidimetric ultracentrifugation.\" We have used turbidimetric ultracentrifugation ot determine the sedimentation coefficient distribution for a sample of human serum very low density lipoproteins. This distribution is compared to that found with conventional schlieren techniques with good agreement.", "contents": "Turbidimetric ultracentrifugation. Application to the study of human serum very low density lipoprotein distributions. In this communication it is shown that the sedimentation coefficient distribution may be accurately measured for very large particles using turbidimetric techniques and the ultraviolet-scanning analytical ultracentrifuge. A principal advantage is that turbidity is a function of the product of concentration and molecular weight; thus, large particles may be observed even when present in very small amounts. We propose to call this method of analysis \"turbidimetric ultracentrifugation.\" We have used turbidimetric ultracentrifugation ot determine the sedimentation coefficient distribution for a sample of human serum very low density lipoproteins. This distribution is compared to that found with conventional schlieren techniques with good agreement."}
{"id": "PMID:190240", "title": "Lipoprotein-mediated regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesteryl ester metabolism in the adrenal gland of the rat.", "content": "In the adrenal gland of the rat, the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme of cholesterol synthesis, is shown to be regulated by cholesteerol carried in plasma lipoproteins. When plasma cholesterol levels were lowered 90% by administration of the drug 4-aminopyrazolopyrimidine, the cholesteryl ester content of the adrenal gland declined by more than 90% and this was associated with a 150- to 200-fold increase in the activity of adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase and a 30-fold increase in cholesterol synthesis from [14C]acetate. The subsequent intravenous infusion of cholesterol contained in either rat or human high density or low density lipoproteins restored the adrenal content of cholesteryl esters and reduced the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase to basal levels. The depletion of adrenal cholesteryl esters and the enhancement in the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase that occurred in the 4-aminopyrazolopyrimidine-treated rat required the action of adrenocorticotropic hormone (ACTH) since neither was observed when ACTH secretion was blocked by administration of dexamethasone. The current data indicate that the low rate of cholesterol synthesis normally observed in the rat adrenal gland is due to a suppression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase that is mediated by plasma lipoproteins.", "contents": "Lipoprotein-mediated regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesteryl ester metabolism in the adrenal gland of the rat. In the adrenal gland of the rat, the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme of cholesterol synthesis, is shown to be regulated by cholesteerol carried in plasma lipoproteins. When plasma cholesterol levels were lowered 90% by administration of the drug 4-aminopyrazolopyrimidine, the cholesteryl ester content of the adrenal gland declined by more than 90% and this was associated with a 150- to 200-fold increase in the activity of adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase and a 30-fold increase in cholesterol synthesis from [14C]acetate. The subsequent intravenous infusion of cholesterol contained in either rat or human high density or low density lipoproteins restored the adrenal content of cholesteryl esters and reduced the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase to basal levels. The depletion of adrenal cholesteryl esters and the enhancement in the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase that occurred in the 4-aminopyrazolopyrimidine-treated rat required the action of adrenocorticotropic hormone (ACTH) since neither was observed when ACTH secretion was blocked by administration of dexamethasone. The current data indicate that the low rate of cholesterol synthesis normally observed in the rat adrenal gland is due to a suppression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase that is mediated by plasma lipoproteins."}
{"id": "PMID:190241", "title": "Enzyme and phospholipid asymmetry in liver microsomal membranes.", "content": "The transverse distribution of enzyme proteins and phospholipids within microsomal membranes was studied by analyzing membrane composition after treatment with proteases and phospholipases. Upon trypsin treatment of closed microsomal vesicles, NADH- and NADPH-cytochrome c reductases as well as cytochrome b5 were solubilized or inactivated, while cytochrome P-450 was partially inactivated. When microsomes were exposed to a concentration of deoxycholate which makes them permeable to macromolecules but does not disrupt the membrane, the detergent alone was sufficient to release four enzymes: nucleoside diphosphatase, esterase, beta-glucuronidase, and a portion of the DT-diaphorase. Introduction of trypsin into the vesicle lumen inactivated glucose-6-phosphatase completely and cytochrome P-450 partially. The rest of this cytochrome, ATPase, AMPase, UDP-glucuronyltransferase, and the remaining 50% of DT-diaphorase activity were not affected by proteolysis from either side of the membrane. Phospholipase A treatment of intact microsomes in the presence of albumin hydrolyzed all of the phosphatidylethanolamine, phosphatidylserine, and 55% of the phosphatidylcholine. From this observation, it was concluded that these lipids are localized in the outer half of the bilayer of the microsomal membrane; Phosphatidylinositol, 45% of the phosphatidylcholine, and sphingomyelin are tentatively assigned to the inner half of this bilayer. It appears that the various enzyme proteins and phospholipids of the microsomal membrane display an asymmetric distribution in the transverse plane.", "contents": "Enzyme and phospholipid asymmetry in liver microsomal membranes. The transverse distribution of enzyme proteins and phospholipids within microsomal membranes was studied by analyzing membrane composition after treatment with proteases and phospholipases. Upon trypsin treatment of closed microsomal vesicles, NADH- and NADPH-cytochrome c reductases as well as cytochrome b5 were solubilized or inactivated, while cytochrome P-450 was partially inactivated. When microsomes were exposed to a concentration of deoxycholate which makes them permeable to macromolecules but does not disrupt the membrane, the detergent alone was sufficient to release four enzymes: nucleoside diphosphatase, esterase, beta-glucuronidase, and a portion of the DT-diaphorase. Introduction of trypsin into the vesicle lumen inactivated glucose-6-phosphatase completely and cytochrome P-450 partially. The rest of this cytochrome, ATPase, AMPase, UDP-glucuronyltransferase, and the remaining 50% of DT-diaphorase activity were not affected by proteolysis from either side of the membrane. Phospholipase A treatment of intact microsomes in the presence of albumin hydrolyzed all of the phosphatidylethanolamine, phosphatidylserine, and 55% of the phosphatidylcholine. From this observation, it was concluded that these lipids are localized in the outer half of the bilayer of the microsomal membrane; Phosphatidylinositol, 45% of the phosphatidylcholine, and sphingomyelin are tentatively assigned to the inner half of this bilayer. It appears that the various enzyme proteins and phospholipids of the microsomal membrane display an asymmetric distribution in the transverse plane."}
{"id": "PMID:190242", "title": "Ultrastructural changes induced by ACTH in normal adrenocortical cells in culture.", "content": "The effects of ACTH, its o-nitrophenyl sulfenyl derivative (NPS-ACTH) and dibutyryl cyclic AMP (dbc AMP) on the ultrastructural morphology of adrenocortical cells of adult rats in monolayer culture have been investigated. NPS-ACTH, which has previously been shown to stimulate steroidogenesis but not cAMP synthesis in adrenal cells, induced the same characteristic transformation of mitochondrial architecture as produced by ACTH or high concentrations of dbcAMP. All three agents caused the disappearance of electron-opaque granules present in the mitochondria of unstimulated cells. It was found that these granules could be extracted with EGTA (ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetate). These results are discussed in the light of the known importance of calcium ions in the actions of ACTH.", "contents": "Ultrastructural changes induced by ACTH in normal adrenocortical cells in culture. The effects of ACTH, its o-nitrophenyl sulfenyl derivative (NPS-ACTH) and dibutyryl cyclic AMP (dbc AMP) on the ultrastructural morphology of adrenocortical cells of adult rats in monolayer culture have been investigated. NPS-ACTH, which has previously been shown to stimulate steroidogenesis but not cAMP synthesis in adrenal cells, induced the same characteristic transformation of mitochondrial architecture as produced by ACTH or high concentrations of dbcAMP. All three agents caused the disappearance of electron-opaque granules present in the mitochondria of unstimulated cells. It was found that these granules could be extracted with EGTA (ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetate). These results are discussed in the light of the known importance of calcium ions in the actions of ACTH."}
{"id": "PMID:190243", "title": "Delayed malignancy and altered growth properties of somatic cell hybrids between rat hepatoma and mouse L-cells.", "content": "Somatic cell hybrids of mouse L-cells with rat HTC cells were studied for their growth properties in vitro and tumorigenicity in vivo. Three hybrid clones were selected for detailed study. All were delayed in tumor formation in nude mice compared with the parent lines despite their varied growth properties in vitro. One clone was sensitive to density dependent inhibition of growth (DDIG) and had a relatively low saturation density. A second clone was not sensitive to DDIG and had a higher saturation density. The third clone had atypical morphology, was insensitive to DDIG, and had a relatively high saturation density. All of the clones studied produced colonies suspended in agarose gel which were much smaller than those of the parents incubated for the same period of time. Only the pattern of growth in agarose gel corresponded to the delayed tumor formation in vivo of the hybrids. Sensitivity to DDIG and saturation density were not consistent with tumor growth. The hybrid clone that was sensitive to DDIG was the only one of the three that had a nearly complete set of chromosomes derived from each of the parents. The chromosome numbers of all three clones were unchanged after growth in agarose or as tumors in the nude mice.", "contents": "Delayed malignancy and altered growth properties of somatic cell hybrids between rat hepatoma and mouse L-cells. Somatic cell hybrids of mouse L-cells with rat HTC cells were studied for their growth properties in vitro and tumorigenicity in vivo. Three hybrid clones were selected for detailed study. All were delayed in tumor formation in nude mice compared with the parent lines despite their varied growth properties in vitro. One clone was sensitive to density dependent inhibition of growth (DDIG) and had a relatively low saturation density. A second clone was not sensitive to DDIG and had a higher saturation density. The third clone had atypical morphology, was insensitive to DDIG, and had a relatively high saturation density. All of the clones studied produced colonies suspended in agarose gel which were much smaller than those of the parents incubated for the same period of time. Only the pattern of growth in agarose gel corresponded to the delayed tumor formation in vivo of the hybrids. Sensitivity to DDIG and saturation density were not consistent with tumor growth. The hybrid clone that was sensitive to DDIG was the only one of the three that had a nearly complete set of chromosomes derived from each of the parents. The chromosome numbers of all three clones were unchanged after growth in agarose or as tumors in the nude mice."}
{"id": "PMID:190244", "title": "Meiotic maturation of mouse oocytes in vitro: inhibition of maturation at specific stages of nuclear progression.", "content": "In vitro studies of meiotic maturation of mouse oocytes have been carried out in the presence of several drugs. The individual steps of nuclear progression, including dissolution of the nuclear (germinal vesicle) membrane, condensation of dictyate chromatin into compact bivalents, formation of the first metaphase spindle, and extrusion of the first polar body, are each susceptible to one or more of these drugs. Germinal vesicle breakdown, the initial morphological feature characteristic of meiotic maturation, is inhibited by dibutyryl cyclic AMP. However, even in the presence of dibutyryl cyclic AMP, the nuclear membrane becomes extremely convoluted and condensation of chromatin is initiated but aborts at a stage short of compact bivalents. Germinal vesicle breakdown and chromatin condensation take place in an apparently normal manner in the presence of puromycin, Colcemid, or cytochalasin B. Nuclear progression is blocked at the circular bivalent stage when oocytes are cultured continuously in the presence of puromycin or Colcemid, whereas oocytes cultured in the presence of cytochalasin B proceed to the first meiotic metaphase, form an apparently normal spindle, and arrest. Emission of a polar body is inhibited by all of these drugs. The inhibitory effects of these drugs on meiotic maturation are reversible to varying degrees dependent upon the duration of exposure to the drug and upon the nature of the drug. These studies suggest that dissolution of the mouse oocyte's germinal vesicle and condensation of chromatin are not dependent upon concomitant protein synthesis or upon microtubules. On the other hand, the complete condensation of chromatin into compact bivalents apparently requires breakdown of the germinal vesicle. Failure of homologous chromosomes to separate after normal alignment on the meiotic spindle in the presence of cytochalasin B suggest that microfilaments may be involved in nuclear progression at this stage of maturation. Cytokinesis, in the form of polar body formation, is blocked when any one of the earlier events of maturation fails to take place.", "contents": "Meiotic maturation of mouse oocytes in vitro: inhibition of maturation at specific stages of nuclear progression. In vitro studies of meiotic maturation of mouse oocytes have been carried out in the presence of several drugs. The individual steps of nuclear progression, including dissolution of the nuclear (germinal vesicle) membrane, condensation of dictyate chromatin into compact bivalents, formation of the first metaphase spindle, and extrusion of the first polar body, are each susceptible to one or more of these drugs. Germinal vesicle breakdown, the initial morphological feature characteristic of meiotic maturation, is inhibited by dibutyryl cyclic AMP. However, even in the presence of dibutyryl cyclic AMP, the nuclear membrane becomes extremely convoluted and condensation of chromatin is initiated but aborts at a stage short of compact bivalents. Germinal vesicle breakdown and chromatin condensation take place in an apparently normal manner in the presence of puromycin, Colcemid, or cytochalasin B. Nuclear progression is blocked at the circular bivalent stage when oocytes are cultured continuously in the presence of puromycin or Colcemid, whereas oocytes cultured in the presence of cytochalasin B proceed to the first meiotic metaphase, form an apparently normal spindle, and arrest. Emission of a polar body is inhibited by all of these drugs. The inhibitory effects of these drugs on meiotic maturation are reversible to varying degrees dependent upon the duration of exposure to the drug and upon the nature of the drug. These studies suggest that dissolution of the mouse oocyte's germinal vesicle and condensation of chromatin are not dependent upon concomitant protein synthesis or upon microtubules. On the other hand, the complete condensation of chromatin into compact bivalents apparently requires breakdown of the germinal vesicle. Failure of homologous chromosomes to separate after normal alignment on the meiotic spindle in the presence of cytochalasin B suggest that microfilaments may be involved in nuclear progression at this stage of maturation. Cytokinesis, in the form of polar body formation, is blocked when any one of the earlier events of maturation fails to take place."}
{"id": "PMID:190245", "title": "Quantitative analysis of disulfiram and its metabolites in human blood by gas-liquid chromatography.", "content": "A simple method is described that permits the direct quantitative determination of carbon disulphide, free diethyldithiocarbamate and disulphides derived from disulfiram in 1 ml of a patient's blood. It is based on a gas chromatographic determination of carbon disulphide produced from diethyldithiocarbamate and disulfiram using the head-space technique and a flame-photometric detector. The method is compared with a recently described spectrophotometric method.", "contents": "Quantitative analysis of disulfiram and its metabolites in human blood by gas-liquid chromatography. A simple method is described that permits the direct quantitative determination of carbon disulphide, free diethyldithiocarbamate and disulphides derived from disulfiram in 1 ml of a patient's blood. It is based on a gas chromatographic determination of carbon disulphide produced from diethyldithiocarbamate and disulfiram using the head-space technique and a flame-photometric detector. The method is compared with a recently described spectrophotometric method."}
{"id": "PMID:190246", "title": "Isotopic fractionation in thin-layer chromatography.", "content": "The thin-layer chromatography of imipramine on silica gel plates was studied in fifteen solvent systems. The mobility of imipramine labeled with deuterium in the methyl groups of the dimethylaminopropyl side chain differs markedly from that of unlabeled imipramine. Partial or complete separations between unlabeled and deuterated imipramine were observed in all basic and neutral solvent systems investigated, but not in weakly acidic solvents. Isotopic fractionations of imipramine were also found on alumina thin-layer plates, but were not detected in cellulose chromatography. In all thin-layer isotopic separations, the unlabeled compound migrates more rapidly than the deuterated molecule. These results can be explained by a stronger basicity of deuterated imipramine relative to its unlabeled counterpart.", "contents": "Isotopic fractionation in thin-layer chromatography. The thin-layer chromatography of imipramine on silica gel plates was studied in fifteen solvent systems. The mobility of imipramine labeled with deuterium in the methyl groups of the dimethylaminopropyl side chain differs markedly from that of unlabeled imipramine. Partial or complete separations between unlabeled and deuterated imipramine were observed in all basic and neutral solvent systems investigated, but not in weakly acidic solvents. Isotopic fractionations of imipramine were also found on alumina thin-layer plates, but were not detected in cellulose chromatography. In all thin-layer isotopic separations, the unlabeled compound migrates more rapidly than the deuterated molecule. These results can be explained by a stronger basicity of deuterated imipramine relative to its unlabeled counterpart."}
{"id": "PMID:190247", "title": "Micro-determination of total phthalate esters in biological samples by gas-liquid chromatography.", "content": "A method was investigated in which all of the phthalate esters in biological samples were determined as phthalic acid by gas-liquid chromatography. The method is based on the separation of phthalate esters from the sample with n-hexane, saponification of the esters with an alkaline ethanolic solution to give phthalic acid, purification of the acid by extraction with diethyl ether and column chromatography using silica gel, and conversion of the acid into bis(2,2,2-trifluoroethyl) phthalate with a 2,2,2-trifluoroethanol solution containing boron trifluoride. The derivative obtained is highly sensitive to an electron-capture detector, giving a sensitivity of 0.1 pg. Biological samples fortified with di(2-ethylhexyl) phthalate at levels of 5-100 ppb were analyzed, with recoveries of 70-100%.", "contents": "Micro-determination of total phthalate esters in biological samples by gas-liquid chromatography. A method was investigated in which all of the phthalate esters in biological samples were determined as phthalic acid by gas-liquid chromatography. The method is based on the separation of phthalate esters from the sample with n-hexane, saponification of the esters with an alkaline ethanolic solution to give phthalic acid, purification of the acid by extraction with diethyl ether and column chromatography using silica gel, and conversion of the acid into bis(2,2,2-trifluoroethyl) phthalate with a 2,2,2-trifluoroethanol solution containing boron trifluoride. The derivative obtained is highly sensitive to an electron-capture detector, giving a sensitivity of 0.1 pg. Biological samples fortified with di(2-ethylhexyl) phthalate at levels of 5-100 ppb were analyzed, with recoveries of 70-100%."}
{"id": "PMID:190248", "title": "Isolation and purification of lithocholic acid metabolites produced by the intestinal microflora.", "content": "Lithocholic acid metabolites produced by the intestinal microflora of rats can be isolated from other endogenous lipids using Sephadex LH-20 column chromatography. Analyses of individual metabolites collected from the column by silica gel coated glass fiber paper chromatography result in the resolution of epimeric 3-hydroxy derivatives. In addition, glass fiber paper chromatography is more sensitive and requires less development time than conventional glass-coated thin-layer plates. Further confirmation of the identity of metabolites is achieved by gas-liquid chromatography, which separates both methyl and ethyl esters of lithocholic and isolithocholic acids.", "contents": "Isolation and purification of lithocholic acid metabolites produced by the intestinal microflora. Lithocholic acid metabolites produced by the intestinal microflora of rats can be isolated from other endogenous lipids using Sephadex LH-20 column chromatography. Analyses of individual metabolites collected from the column by silica gel coated glass fiber paper chromatography result in the resolution of epimeric 3-hydroxy derivatives. In addition, glass fiber paper chromatography is more sensitive and requires less development time than conventional glass-coated thin-layer plates. Further confirmation of the identity of metabolites is achieved by gas-liquid chromatography, which separates both methyl and ethyl esters of lithocholic and isolithocholic acids."}
{"id": "PMID:190249", "title": "Separation of naphthoquinones and lipophilic vitamins by gel and thin-layer chromatography.", "content": "A separation of naphthoquinones on silica gel and on silica gel impregnated with polyethylene glycol 200 by thin-layer chromatography was compared with gel permeation chromatography (GPC) on styrene-divinylbenzene copolymer S-832-gel using tetrahydrofuran as mobile phase. Factors affecting the separations attainable are discussed, and it is concluded that GPC is a suitable method for the determination of K vitamins in natural materials.", "contents": "Separation of naphthoquinones and lipophilic vitamins by gel and thin-layer chromatography. A separation of naphthoquinones on silica gel and on silica gel impregnated with polyethylene glycol 200 by thin-layer chromatography was compared with gel permeation chromatography (GPC) on styrene-divinylbenzene copolymer S-832-gel using tetrahydrofuran as mobile phase. Factors affecting the separations attainable are discussed, and it is concluded that GPC is a suitable method for the determination of K vitamins in natural materials."}
{"id": "PMID:190251", "title": "Plasma pregnenolone and 17-OH-pregnenolone in patients with adrenal tumors, ACTH excess, or idiopathic hirsutism.", "content": "Plasma levels of the delta5-pregnenes, pregenolone and 17-OH-pregnenolone, were measured in patients with disordered steroidogenesis. While 17-OH-pregnenolone was within the normal range in patients with hypercortisolemia due to Cushing's disease, ectopic ACTH or adrenal adenrenal adenoma, 4 of 6 patients with an adrenal carcinoma had elevated levels of this precursor. Thus, elevated plasma 17-OH-pregnenolone levels in patients with Cushing's syndrome indicate adrenal carcinoma, although a normal value does not exclude this diagnosis. Abnormal resistance of delta5-pregnenes to suppression with dexamethasone proved useful in detecting the presence of residual tumor in the post-operative evaluation of adrenal carcinoma. Basal plasma pregnenolone was within the normal range in 19 of 20 patients with Cushing's disease and was invariably normal in patients with other varieties of hypercortisolism. Since acute administration of ACTH causes marked elevation of delta5-pregnene levels while patients with chronic ACTH excess (Cushing's disease and ectopic ACTH production) have normal levels, it is suggested that ACTH has a chronic influence on the intraadrenal utilization of delta5-pregnenes in addition to stimulating their formation. In pre-menopausal women with idiopathic hirsutism, basal levels of both delta5-pregnenes were elevated (P less than 0.001). Following dexamethasone administration the absolute decrease in delta5-pregnenes levels was greater than that seen in normal subjects. This observation indicates that the metabolism of delta5-pregnenes is abnormal in patients with idiopathic hirsutism.", "contents": "Plasma pregnenolone and 17-OH-pregnenolone in patients with adrenal tumors, ACTH excess, or idiopathic hirsutism. Plasma levels of the delta5-pregnenes, pregenolone and 17-OH-pregnenolone, were measured in patients with disordered steroidogenesis. While 17-OH-pregnenolone was within the normal range in patients with hypercortisolemia due to Cushing's disease, ectopic ACTH or adrenal adenrenal adenoma, 4 of 6 patients with an adrenal carcinoma had elevated levels of this precursor. Thus, elevated plasma 17-OH-pregnenolone levels in patients with Cushing's syndrome indicate adrenal carcinoma, although a normal value does not exclude this diagnosis. Abnormal resistance of delta5-pregnenes to suppression with dexamethasone proved useful in detecting the presence of residual tumor in the post-operative evaluation of adrenal carcinoma. Basal plasma pregnenolone was within the normal range in 19 of 20 patients with Cushing's disease and was invariably normal in patients with other varieties of hypercortisolism. Since acute administration of ACTH causes marked elevation of delta5-pregnene levels while patients with chronic ACTH excess (Cushing's disease and ectopic ACTH production) have normal levels, it is suggested that ACTH has a chronic influence on the intraadrenal utilization of delta5-pregnenes in addition to stimulating their formation. In pre-menopausal women with idiopathic hirsutism, basal levels of both delta5-pregnenes were elevated (P less than 0.001). Following dexamethasone administration the absolute decrease in delta5-pregnenes levels was greater than that seen in normal subjects. This observation indicates that the metabolism of delta5-pregnenes is abnormal in patients with idiopathic hirsutism."}
{"id": "PMID:190252", "title": "Response of several adrenal steroids to ACTH stimulation in essential hypertension.", "content": "Plasma concentrations of progesterone (P), deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OH P), corticosterone (B), deoxycortisol (S), cortisol (F), and aldosterone were measured in 8 control subjects and in 10 patients with low and normal renin essential hypertension (EH) before and 4 and 8 h after an iv infusion of 25 units of ACTH. Secretion rates of 18-hydroxy-11-deoxycorticosterone (18-OH DOC) were measured for the 24 h prior to and the day of the ACTH infusions. The hypertensive patients had significantly higher plasma levels of aldosterone, DOC and S after ACTH than the controls, whereas plasma B levels were significantly lower. The low renin subgroup considered separately had significantly higher plasma levels of aldosterone and DOC than controls, and higher levels of B and lower levels of F than the normal renin subgroup in response to ACTH. Although not significantly different, the plasma levels of P and the secretion rate of 18-OH DOC tended to be higher, and plasma 17-OH P and F levels lower after ACTH in patients with EH than in controls. The low renin subgroup tended to have the highest plasma S levels and 18-OH DOC secretory rates and lowest F levels. Estimations of adrenal 11beta-hydroxylating efficiency in response to ACTH in patients and controls by plasma steroid ratios revealed significantly lower B/DOC ratios in both low and normal renin patients compared to controls, supported by somewhat lower F/S ratios in these patients, especially those in the low renin subgroup. Altered 17-hydroxylating efficiency seen by significantly lower 17-OH P/P ratios were also found in those with EH, supported by somewhat lower F/B and S/DOC ratios in these patients, agian especially in the low renin subgroup. These data are compatible with a pattern of altered adrenocortical steroid biosynthesis in essential hypertension bearing features similar to adrenal 11beta and 17alpha-hydroxylation deficiencies.", "contents": "Response of several adrenal steroids to ACTH stimulation in essential hypertension. Plasma concentrations of progesterone (P), deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OH P), corticosterone (B), deoxycortisol (S), cortisol (F), and aldosterone were measured in 8 control subjects and in 10 patients with low and normal renin essential hypertension (EH) before and 4 and 8 h after an iv infusion of 25 units of ACTH. Secretion rates of 18-hydroxy-11-deoxycorticosterone (18-OH DOC) were measured for the 24 h prior to and the day of the ACTH infusions. The hypertensive patients had significantly higher plasma levels of aldosterone, DOC and S after ACTH than the controls, whereas plasma B levels were significantly lower. The low renin subgroup considered separately had significantly higher plasma levels of aldosterone and DOC than controls, and higher levels of B and lower levels of F than the normal renin subgroup in response to ACTH. Although not significantly different, the plasma levels of P and the secretion rate of 18-OH DOC tended to be higher, and plasma 17-OH P and F levels lower after ACTH in patients with EH than in controls. The low renin subgroup tended to have the highest plasma S levels and 18-OH DOC secretory rates and lowest F levels. Estimations of adrenal 11beta-hydroxylating efficiency in response to ACTH in patients and controls by plasma steroid ratios revealed significantly lower B/DOC ratios in both low and normal renin patients compared to controls, supported by somewhat lower F/S ratios in these patients, especially those in the low renin subgroup. Altered 17-hydroxylating efficiency seen by significantly lower 17-OH P/P ratios were also found in those with EH, supported by somewhat lower F/B and S/DOC ratios in these patients, agian especially in the low renin subgroup. These data are compatible with a pattern of altered adrenocortical steroid biosynthesis in essential hypertension bearing features similar to adrenal 11beta and 17alpha-hydroxylation deficiencies."}
{"id": "PMID:190253", "title": "Metabolic responses to the administration of angiotensin II, K and ACTH in two salt-wasting syndromes.", "content": "Metabolic responses to the administration of Angiotensin II, K and ACTH are described in two salt-wasting syndromes: hypoaldosteronism in Jews from Iran, which is characterized by an enzymic block in the conversion of 18-hydroxycorticosterone to aldosteron; and pseudohypoaldosteronism, a disorder in which aldosterone secretion is high in association with renal tubular unresponsiveness to mineralocorticoids. The response of plasma and urinary aldosterone to K and ACTH is qualitatively normal in hypoaldosteronism; however, infusion of Angiotensin II, in a dose that was pressor and elevated aldosterone levels threefold in control subjects, was only pressor in hypoaldosteronism. In pseudohypoaldosteronism, plasma and urinary aldosterone respond to Angiotensin II, K and ACTH, notwithstanding very high basal hormonal levels.", "contents": "Metabolic responses to the administration of angiotensin II, K and ACTH in two salt-wasting syndromes. Metabolic responses to the administration of Angiotensin II, K and ACTH are described in two salt-wasting syndromes: hypoaldosteronism in Jews from Iran, which is characterized by an enzymic block in the conversion of 18-hydroxycorticosterone to aldosteron; and pseudohypoaldosteronism, a disorder in which aldosterone secretion is high in association with renal tubular unresponsiveness to mineralocorticoids. The response of plasma and urinary aldosterone to K and ACTH is qualitatively normal in hypoaldosteronism; however, infusion of Angiotensin II, in a dose that was pressor and elevated aldosterone levels threefold in control subjects, was only pressor in hypoaldosteronism. In pseudohypoaldosteronism, plasma and urinary aldosterone respond to Angiotensin II, K and ACTH, notwithstanding very high basal hormonal levels."}
{"id": "PMID:190254", "title": "Plasma ACTH and cortisol responses to TRF, vasopressin or hypoglycemia in cushing's disease and nelson's syndrome.", "content": "The response of plasma ACTH and/or cortisol concentrations to thyrotropin-releasing-factor  (TRF), vasopressin, and insulin administration was determined in 5 patients with Nelson's syndrome and 12 patients with untreated Cushing's disease. TRF administration was associated with a mean increment of 267 pg/ml in plasma ACTH concentrations in patients with Nelson's syndrome, and of 42 pg/ml in patients with Cushing's disease. The increment in plasma cortisol concentrations in the latter group was 12 mug%. No ACTH or cortisol response was observed in normal subjects. Patients with Cushing's disease or Nelson's syndrome exhibited significantly greater increments in plasma ACTH concentrations in response to vasopressin administration (P less than .05, P less than .02 respectively) than did normal subjects; the increment in cortisol concentration was also greater, (P less than .05), in patients with Cushing's disease than in normal subjects. No significant difference was present between patients with Cushing's disease and Nelson's syndrome with regard to the magnitude of the ACTH response to vasopressin administration. In contrast, the increment in plasma cortisol and plasma ACTH concentrations following insulin induced hypoglycemia was significantly less in patients with Cushing's disease than seen in normal subjects, (P less than .001, P less than .05 respectively); while this stimulus was associated with a significantly greater increment in plasma ACTH concentrations in patients with Nelson's syndrome as compared to that seen in normal subjects, (P less than .01) and in patients with Cushing's disease (P less than .01). These findings indicate that pituitary function in patients with Nelson's syndrome is not autonomous and suggest the possibility that altered central nervous regulatory mechanism might play a role in the etiology of the pituitary tumors which are frequently associated with this syndrome. The TRF induced rise in plasm cortisol and ACTH concentrations in patients with Cushing's disease and Nelson's syndrome suggests the possibility of altered hypothalamic or pituitary receptors in such patients.", "contents": "Plasma ACTH and cortisol responses to TRF, vasopressin or hypoglycemia in cushing's disease and nelson's syndrome. The response of plasma ACTH and/or cortisol concentrations to thyrotropin-releasing-factor  (TRF), vasopressin, and insulin administration was determined in 5 patients with Nelson's syndrome and 12 patients with untreated Cushing's disease. TRF administration was associated with a mean increment of 267 pg/ml in plasma ACTH concentrations in patients with Nelson's syndrome, and of 42 pg/ml in patients with Cushing's disease. The increment in plasma cortisol concentrations in the latter group was 12 mug%. No ACTH or cortisol response was observed in normal subjects. Patients with Cushing's disease or Nelson's syndrome exhibited significantly greater increments in plasma ACTH concentrations in response to vasopressin administration (P less than .05, P less than .02 respectively) than did normal subjects; the increment in cortisol concentration was also greater, (P less than .05), in patients with Cushing's disease than in normal subjects. No significant difference was present between patients with Cushing's disease and Nelson's syndrome with regard to the magnitude of the ACTH response to vasopressin administration. In contrast, the increment in plasma cortisol and plasma ACTH concentrations following insulin induced hypoglycemia was significantly less in patients with Cushing's disease than seen in normal subjects, (P less than .001, P less than .05 respectively); while this stimulus was associated with a significantly greater increment in plasma ACTH concentrations in patients with Nelson's syndrome as compared to that seen in normal subjects, (P less than .01) and in patients with Cushing's disease (P less than .01). These findings indicate that pituitary function in patients with Nelson's syndrome is not autonomous and suggest the possibility that altered central nervous regulatory mechanism might play a role in the etiology of the pituitary tumors which are frequently associated with this syndrome. The TRF induced rise in plasm cortisol and ACTH concentrations in patients with Cushing's disease and Nelson's syndrome suggests the possibility of altered hypothalamic or pituitary receptors in such patients."}
{"id": "PMID:190255", "title": "Bilateral testicular tumors in congenital adrenal hyperplasia.", "content": "A 22-year-old male with bilateral testicular tumors and the 21-hydroxylase variety of congenital adrenal hyperplasia (CAH) was studied. Preoperatively, on his usual glucocorticoid regimen, his urinary pregnanetriol excretion was increased (8.0-23.5 mg/day), serum LH and FSH were normal to increased (14.3-28.7 mIU/ml and 13.2-19.5 mIU/ml, respectively) and testosterone (T) was normal to decreased (176-600 ng/dl). At surgery, testicular vein concentrations of 17-alpha-hydroxyprogesterone (17-OHP) and adnrostenedione (delta) were increased (30.1 mug/dl and 38.3 mug/dl respectively) while T was decreased (1,503 ng/dl); a positive peripheral vein--testicular vein gradient was not seen for these steroids. Following injection of 10 U of crystalline ACTH into the testicular artery; testicular vein concentrations of 17-OHP, delta and T increased to 729 mug/dl, 2,390 mug/dl and 9,660 ng/dl respectively. Microscopic examination of the testes revealed multinodular tumors composed of polygonal or rounded eosinophilic cells, arranged in cords, nests and clusters. The tumors extended from the hilus and compressed the adjacent testicular tissue. Electron microscopic examination of the tumors showed features, common to steroid-secreting tissues, with abundant smooth endoplasmic reticulum in close proximity to mitochondria which was moderate in number. The adjacent testicular tissue was composed of immature tubules with normally developed Leydig cells in the interstitial tissues. From these data and a survey of previous works, it was postulated that these tumors were dependent upon ACTH for growth and steroid secretion. In view of the high serum LH concentration seen in association with incomplete suppression of adrenal steroid secretion in this study and the association of evidence of gonadotropin secretion with testicular tumors in other CAH patients, LH may also have contributed to the growth of these tumors.", "contents": "Bilateral testicular tumors in congenital adrenal hyperplasia. A 22-year-old male with bilateral testicular tumors and the 21-hydroxylase variety of congenital adrenal hyperplasia (CAH) was studied. Preoperatively, on his usual glucocorticoid regimen, his urinary pregnanetriol excretion was increased (8.0-23.5 mg/day), serum LH and FSH were normal to increased (14.3-28.7 mIU/ml and 13.2-19.5 mIU/ml, respectively) and testosterone (T) was normal to decreased (176-600 ng/dl). At surgery, testicular vein concentrations of 17-alpha-hydroxyprogesterone (17-OHP) and adnrostenedione (delta) were increased (30.1 mug/dl and 38.3 mug/dl respectively) while T was decreased (1,503 ng/dl); a positive peripheral vein--testicular vein gradient was not seen for these steroids. Following injection of 10 U of crystalline ACTH into the testicular artery; testicular vein concentrations of 17-OHP, delta and T increased to 729 mug/dl, 2,390 mug/dl and 9,660 ng/dl respectively. Microscopic examination of the testes revealed multinodular tumors composed of polygonal or rounded eosinophilic cells, arranged in cords, nests and clusters. The tumors extended from the hilus and compressed the adjacent testicular tissue. Electron microscopic examination of the tumors showed features, common to steroid-secreting tissues, with abundant smooth endoplasmic reticulum in close proximity to mitochondria which was moderate in number. The adjacent testicular tissue was composed of immature tubules with normally developed Leydig cells in the interstitial tissues. From these data and a survey of previous works, it was postulated that these tumors were dependent upon ACTH for growth and steroid secretion. In view of the high serum LH concentration seen in association with incomplete suppression of adrenal steroid secretion in this study and the association of evidence of gonadotropin secretion with testicular tumors in other CAH patients, LH may also have contributed to the growth of these tumors."}
{"id": "PMID:190256", "title": "Adenylate cyclase of GH and ACTH producing tumors of human: activation by non-specific hormones and other bioactive substances.", "content": "The adenylate cyclase responses of the human GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors to TRH, LH-RH, biogenic amines, peptides hormones, PGE1 and rat median eminence extract (MEE) have been examined. Out of 4 GH producing pituitary adenomas obtained from patients with active acromegaly at hypophysectomy two were stimulated by TRH, two by LH-RH, three by norepinephrine, one by dopamine, four by PGE1 and none by serotonin. Glucagon stimulated the adenylate cyclase in one of three and MEE in both of two tested. The positive responses of paradoxical GH release after TRH and/or LH-RH before surgery in these patients coincidentally related to the response of adenylate cyclase of each pituitary adenoma. There seems, however, to be no consistent correlation between the adenylate cyclase responses to biogenic amines and the GH release after L-Dopa or 5-hydroxytroptophan tested. The adenylate cyclase of a pituitary adenoma from case of Cushing's disease was stimulated by LH-RH, norepinephrine glucagon and MEE but not by TRH. Plasma levels of ACTH, beta-MSH and cortisol increased after LH-RH but not after TRH in this patient before hypophysectomy. The adenylate cyclase of two ectopic ACTH producing tumors (gastric carcinoid and malignant thymoma) was activated by TRH, LH-RH, norepinephrine, epinephrine, serotonin, PGE1 and MEE. These results indicate the presence of multiple hormone receptors in GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors, and suggest that the paradoxical GH or ACTH release after TRH and/or LH-RH injection in acromegaly and Cushing's syndrome might be caused by an alteration of the cellular membrane receptors of the pituitary adenomas.", "contents": "Adenylate cyclase of GH and ACTH producing tumors of human: activation by non-specific hormones and other bioactive substances. The adenylate cyclase responses of the human GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors to TRH, LH-RH, biogenic amines, peptides hormones, PGE1 and rat median eminence extract (MEE) have been examined. Out of 4 GH producing pituitary adenomas obtained from patients with active acromegaly at hypophysectomy two were stimulated by TRH, two by LH-RH, three by norepinephrine, one by dopamine, four by PGE1 and none by serotonin. Glucagon stimulated the adenylate cyclase in one of three and MEE in both of two tested. The positive responses of paradoxical GH release after TRH and/or LH-RH before surgery in these patients coincidentally related to the response of adenylate cyclase of each pituitary adenoma. There seems, however, to be no consistent correlation between the adenylate cyclase responses to biogenic amines and the GH release after L-Dopa or 5-hydroxytroptophan tested. The adenylate cyclase of a pituitary adenoma from case of Cushing's disease was stimulated by LH-RH, norepinephrine glucagon and MEE but not by TRH. Plasma levels of ACTH, beta-MSH and cortisol increased after LH-RH but not after TRH in this patient before hypophysectomy. The adenylate cyclase of two ectopic ACTH producing tumors (gastric carcinoid and malignant thymoma) was activated by TRH, LH-RH, norepinephrine, epinephrine, serotonin, PGE1 and MEE. These results indicate the presence of multiple hormone receptors in GH or ACTH producing pituitary adenomas and ectopic ACTH producing tumors, and suggest that the paradoxical GH or ACTH release after TRH and/or LH-RH injection in acromegaly and Cushing's syndrome might be caused by an alteration of the cellular membrane receptors of the pituitary adenomas."}
{"id": "PMID:190257", "title": "Adenosine 3'5'-cyclic monophosphate dependent protein kinase in human adrenocortical tumors.", "content": "Protein kinase activity has been studied in four human adrenocortical tumors and compared to the one of the normal human adrenal. In two cases where the lack of action of ACTH was related to an anomaly of ACTH receptor, the protein kinase activity was normal. In the other two cases the ACTH receptor was normal, but the protein kinase activity was different from that of the normal adrenal. In one of these cases where the steroidogenesis response of isolated tumor cells to ACTH and DcAMP was higher than in normal adrenal, basal and cAMP stimulated protein kinase activities were significantly higher than those of the normal adrenal, but the activation constants of both nucleotides were similar to those of the normal gland. In the other case, the basal and the cAMP stimulated protein kinase activities were significantly lower, as well as the activation constant of cAMP. However, the binding affinity of 3H-cAMP was normal. Normal adrenal cytosol contains three protein kinases, as resolved by DEAE-cellulose, two of which designated I and II, are cAMP-dependent. The DEAE-cellulose chromatography of the last tumor showed a loss of isoenzyme II. In addition, the protein kinase eluted at the same molarity as that of isoenzyme I of the normal adrenal was not activated by cAMP. Therefore, the lack of response to ACTH of some adrenocortical human tumors may be attributed either to an anomaly of the ACTH receptor or to some defect of the cAMP-dependent protein kinase.", "contents": "Adenosine 3'5'-cyclic monophosphate dependent protein kinase in human adrenocortical tumors. Protein kinase activity has been studied in four human adrenocortical tumors and compared to the one of the normal human adrenal. In two cases where the lack of action of ACTH was related to an anomaly of ACTH receptor, the protein kinase activity was normal. In the other two cases the ACTH receptor was normal, but the protein kinase activity was different from that of the normal adrenal. In one of these cases where the steroidogenesis response of isolated tumor cells to ACTH and DcAMP was higher than in normal adrenal, basal and cAMP stimulated protein kinase activities were significantly higher than those of the normal adrenal, but the activation constants of both nucleotides were similar to those of the normal gland. In the other case, the basal and the cAMP stimulated protein kinase activities were significantly lower, as well as the activation constant of cAMP. However, the binding affinity of 3H-cAMP was normal. Normal adrenal cytosol contains three protein kinases, as resolved by DEAE-cellulose, two of which designated I and II, are cAMP-dependent. The DEAE-cellulose chromatography of the last tumor showed a loss of isoenzyme II. In addition, the protein kinase eluted at the same molarity as that of isoenzyme I of the normal adrenal was not activated by cAMP. Therefore, the lack of response to ACTH of some adrenocortical human tumors may be attributed either to an anomaly of the ACTH receptor or to some defect of the cAMP-dependent protein kinase."}
{"id": "PMID:190258", "title": "Renal effects of native parathyroid hormone and synthetic biologically active fragments in pseudohypoparathyroidism and hypoparathyroidism.", "content": "To gain further insight into the biological significance of parathyroid hormone (PTH) metabolism, native parathyroid hormone and synthetic peptides, similar to PTH metabolites generated in vivo, have been given intravenously to human subjects. The resultant changes in renal excretion of adenosine 6':5' monophosphate (cyclic AMP) and inorganic phosphate have been measured in five pseudohypoparathyroid, four hypoparathyroid, and one pseudopseudohypoparathyroid patient. As anticipated, native PTH promptly increased urinary cyclic AMP and phosphate excretion in the hypoparathyroid and pseudo-pseudohypoparathyroid patients, and had little or no effect on their excretion in the pseudohypoparathyroid patients. Synthetic bovine parathyroid hormone 1-34 and synthetic human parathyroid hormone 1-34 had effects essentially identical to each other and to native PTH. We conclude that the PTH resistance of pseudohypoparathyroidism is probably not caused by a defect in PTH metabolism. We further conclude that synthetic human or bovine parathyroid hormone 1-34 could be used for diagnostic evaluation of patients.", "contents": "Renal effects of native parathyroid hormone and synthetic biologically active fragments in pseudohypoparathyroidism and hypoparathyroidism. To gain further insight into the biological significance of parathyroid hormone (PTH) metabolism, native parathyroid hormone and synthetic peptides, similar to PTH metabolites generated in vivo, have been given intravenously to human subjects. The resultant changes in renal excretion of adenosine 6':5' monophosphate (cyclic AMP) and inorganic phosphate have been measured in five pseudohypoparathyroid, four hypoparathyroid, and one pseudopseudohypoparathyroid patient. As anticipated, native PTH promptly increased urinary cyclic AMP and phosphate excretion in the hypoparathyroid and pseudo-pseudohypoparathyroid patients, and had little or no effect on their excretion in the pseudohypoparathyroid patients. Synthetic bovine parathyroid hormone 1-34 and synthetic human parathyroid hormone 1-34 had effects essentially identical to each other and to native PTH. We conclude that the PTH resistance of pseudohypoparathyroidism is probably not caused by a defect in PTH metabolism. We further conclude that synthetic human or bovine parathyroid hormone 1-34 could be used for diagnostic evaluation of patients."}
{"id": "PMID:190259", "title": "Corticotropin-releasing factor-like activity in ACTH producing tumors.", "content": "Corticotropin-releasing factor (CRF)-like activity in two different kinds of ACTH-producing tumors (human ectopic ACTH-producing colonic cancer and rat MtT/F4 tumor) was determined by an in vitro method using isolated normal rat pituitary cells. The ACTH content of the post mortem colonic cancer was 5.5 ng/g w.wt. The ACTH content of the medium of MtT/F4 tumor cells was 153+/-32 pg/10(5) cells. The ACTH content of MtT/F4 tumor cell suspensions was elevated with increasing doses of hypothalamic median eminence extract (HME). The response of MtT/F4 tumor cells to HME was suppressed by 1 mug/ml of dexamethasone. Extracts of colonic cancer, MtT/F4 tumor and HME produced elevation of the ACTH content of the medium of isolated rat pituitary cells. The CRF-like activities of two kinds of tumor extracts in multiple dilutions ran parallel to that of HME. The CRF-like activities were 0.037 HME equiv/mg w.wt in MtT/F4 tumor and 0.052 HME equiv/mg w.wt. in colonic cancer. These results demonstrated that CRF-like activity existed in these two kinds of ACTH-producing tumors.", "contents": "Corticotropin-releasing factor-like activity in ACTH producing tumors. Corticotropin-releasing factor (CRF)-like activity in two different kinds of ACTH-producing tumors (human ectopic ACTH-producing colonic cancer and rat MtT/F4 tumor) was determined by an in vitro method using isolated normal rat pituitary cells. The ACTH content of the post mortem colonic cancer was 5.5 ng/g w.wt. The ACTH content of the medium of MtT/F4 tumor cells was 153+/-32 pg/10(5) cells. The ACTH content of MtT/F4 tumor cell suspensions was elevated with increasing doses of hypothalamic median eminence extract (HME). The response of MtT/F4 tumor cells to HME was suppressed by 1 mug/ml of dexamethasone. Extracts of colonic cancer, MtT/F4 tumor and HME produced elevation of the ACTH content of the medium of isolated rat pituitary cells. The CRF-like activities of two kinds of tumor extracts in multiple dilutions ran parallel to that of HME. The CRF-like activities were 0.037 HME equiv/mg w.wt in MtT/F4 tumor and 0.052 HME equiv/mg w.wt. in colonic cancer. These results demonstrated that CRF-like activity existed in these two kinds of ACTH-producing tumors."}
{"id": "PMID:190260", "title": "Adenosine-3',5'-monophosphate in the plasma from human pregnancy.", "content": "Adenosine-3',5'-monophosphate (cyclic AMP) concentration was measured in plasma from nonpregnant women; women in the 7-41 weeks of normal pregnancy; during labor; and 5-7 h postpartum. The cyclic AMP levels in the course of normal pregnancy showed an initial peak volume at 14 weeks. After falling to nonpregnant level at 18 weeks, it began to rise steadily and reached a second peak at 34 weeks. A gradual decline was then followed until labor. The postpartum plasma concentration was significantly lower than the nonpregnant level. A similar pattern was found in serial studies in 4 women of normal pregnancy. Sequential cyclic AMP measurement in 5 hypertensive pregnancies showed a markedly elevated level during 16-26 weeks, but became comparable to normal pregnancy values thereafter. In the only preeclamptic patient studied, cyclic AMP was elevated in the 16-27th weeks although no clinical symptom was found until the 31st week. The study showed that the plasma cyclic AMP level in normal pregnancy becomes elevated above nonpregnant  level at the end of the first and during the third trimesters. However, this profile appeared to be altered in pregnancies complicated by hypertension.", "contents": "Adenosine-3',5'-monophosphate in the plasma from human pregnancy. Adenosine-3',5'-monophosphate (cyclic AMP) concentration was measured in plasma from nonpregnant women; women in the 7-41 weeks of normal pregnancy; during labor; and 5-7 h postpartum. The cyclic AMP levels in the course of normal pregnancy showed an initial peak volume at 14 weeks. After falling to nonpregnant level at 18 weeks, it began to rise steadily and reached a second peak at 34 weeks. A gradual decline was then followed until labor. The postpartum plasma concentration was significantly lower than the nonpregnant level. A similar pattern was found in serial studies in 4 women of normal pregnancy. Sequential cyclic AMP measurement in 5 hypertensive pregnancies showed a markedly elevated level during 16-26 weeks, but became comparable to normal pregnancy values thereafter. In the only preeclamptic patient studied, cyclic AMP was elevated in the 16-27th weeks although no clinical symptom was found until the 31st week. The study showed that the plasma cyclic AMP level in normal pregnancy becomes elevated above nonpregnant  level at the end of the first and during the third trimesters. However, this profile appeared to be altered in pregnancies complicated by hypertension."}
{"id": "PMID:190261", "title": "Characteristics of high molecular weight insulins in insulinoma patients.", "content": "These studies were undertaken to characterize the high molecular weight immunoreactive insulins in plasma and tumor extracts of two patients with insulinoma, and to determine whether they are biosynthetic precursors of proinsulin. Plasma was chromatographed on a Sephadex G-50 column and fractions assayed for IRI. Three peaks were observed, one in the void volume region (6%), a peak in the proinsulin region (25%), and the largest peak comigrating with insulin standard (69%). Insulinoma slices were incubated for 4 h and high molecular weight IRI was observed in chromatographed extracts of the tumor, as well as in extracts of the incubation medium, which comprised up to 3% of the total IRI. Gel filtration chromatography of a pre-operative fasting plasma from the second patient revealed a heterogeneous distribution of IRI, with approximately 53% in the high molecular weight region. At surgery an insulinoma was removed. Slices were incubated for 4 h with 14C-amino acids and extracts chromatogrphed. 14C-labeled protein was observed in the V0, and in the proinsulin and insulin regions. These 14C-labeled proteins were precipitated with anti-insulin serum, and it was determined that whereas 60-90% of 14C-protein in the proinsulin-insulin region was precipitated, virtually none of the 14C-protein in the V0 was immunoprecipitated with anti-insulin serum. The specific activities (CPM precipitated by anti-insulin serum/muU IRI) were 1, 11.4, and 3.1 for V0, proinsulin, and insulin regions, respectively. These results suggest that proinsulin is synthesized first, followed by insulin, and then the high molecular weight IRI. The high molecular weight IRI is not a biosynthetic precursor of proinsulin. Rechromatography of the high-molecular weight IRI in the presence of 8M urea dissociated 90% into smaller immunoreactive components which chromatographed in the proinsulin and insulin region. It was concluded that high molecular weight IRI's are present in plasma, tumor extracts, and incubation medium from insulinoma patients. These high molecular weight IRI's are not biosynthetic precursors, but either aggregates of proinsulin and insulin, or insulin bound to larger proteins. These studies do not rule out the existence in humans of a smaller rapidly-turning over precursor to proinsulin similar to the pre-proinsulin discovered in a rat insulinoma by Chan et al.", "contents": "Characteristics of high molecular weight insulins in insulinoma patients. These studies were undertaken to characterize the high molecular weight immunoreactive insulins in plasma and tumor extracts of two patients with insulinoma, and to determine whether they are biosynthetic precursors of proinsulin. Plasma was chromatographed on a Sephadex G-50 column and fractions assayed for IRI. Three peaks were observed, one in the void volume region (6%), a peak in the proinsulin region (25%), and the largest peak comigrating with insulin standard (69%). Insulinoma slices were incubated for 4 h and high molecular weight IRI was observed in chromatographed extracts of the tumor, as well as in extracts of the incubation medium, which comprised up to 3% of the total IRI. Gel filtration chromatography of a pre-operative fasting plasma from the second patient revealed a heterogeneous distribution of IRI, with approximately 53% in the high molecular weight region. At surgery an insulinoma was removed. Slices were incubated for 4 h with 14C-amino acids and extracts chromatogrphed. 14C-labeled protein was observed in the V0, and in the proinsulin and insulin regions. These 14C-labeled proteins were precipitated with anti-insulin serum, and it was determined that whereas 60-90% of 14C-protein in the proinsulin-insulin region was precipitated, virtually none of the 14C-protein in the V0 was immunoprecipitated with anti-insulin serum. The specific activities (CPM precipitated by anti-insulin serum/muU IRI) were 1, 11.4, and 3.1 for V0, proinsulin, and insulin regions, respectively. These results suggest that proinsulin is synthesized first, followed by insulin, and then the high molecular weight IRI. The high molecular weight IRI is not a biosynthetic precursor of proinsulin. Rechromatography of the high-molecular weight IRI in the presence of 8M urea dissociated 90% into smaller immunoreactive components which chromatographed in the proinsulin and insulin region. It was concluded that high molecular weight IRI's are present in plasma, tumor extracts, and incubation medium from insulinoma patients. These high molecular weight IRI's are not biosynthetic precursors, but either aggregates of proinsulin and insulin, or insulin bound to larger proteins. These studies do not rule out the existence in humans of a smaller rapidly-turning over precursor to proinsulin similar to the pre-proinsulin discovered in a rat insulinoma by Chan et al."}
{"id": "PMID:190262", "title": "Assessment of 11beta-hydroxylase activity with plasma corticosterone, deoxycorticosterone, cortisol, and deoxycortisol: role of ACTH and angiotensin.", "content": "In this study we evaluated the role of ACTH and angiotensin on regulation of activities of 11beta-hydroxylases of the adrenal cortex. The ratio of the plasma concentrations of 11 deoxycorticosterone (DOC) to plasma corticosterone (B) reflected the activity of the enzyme of the B and/or aldosterone pathways, and the ratio of plasma 11-deoxycortisol (S) to plasma cortisol (F) as the activity of the enzyme in the F pathway. In normal subjects, both ratios were significantly lower at 0800-0900 h (Doc to B, .01+/-.004, mean+/-SE, n=10; and S to F, .01+/-.003) than at 2000 h (DOC to B, .028+/-.024 and S to F, .015+/-.005). The plasma levels of DOC, B, S and F were all significantly lower at 2000-2100 h than at 0800-0900 h. In contrast 9 patients with Cushing's syndrome exhibited no diurnal change in the ratios. The ratios increased substantially following dexamethasone or metyrapone administration. A high or low salt diet and an angiotensin infusion produced no significant effect on the ratios. The plasma concentration of all four steroids was increased by more than 50% by an infusion of angiotensin. Four hours after administration of 80 mg of Lasix at 0800 h to 10 normal subjects, the ratios of DOC to B and S to F increased significantly (P less than .02), an effect possibly related to a decreased secretion of ACTH. 1) 11beta-hydroxylase activity of the B and/or aldosterone and F pathways appears to change in parallel with ACTH secretion, and 2) although angiotensin stimulates steroidogenesis of the pathways, it has no apparent effect on 11beta-hydroxylase activity.", "contents": "Assessment of 11beta-hydroxylase activity with plasma corticosterone, deoxycorticosterone, cortisol, and deoxycortisol: role of ACTH and angiotensin. In this study we evaluated the role of ACTH and angiotensin on regulation of activities of 11beta-hydroxylases of the adrenal cortex. The ratio of the plasma concentrations of 11 deoxycorticosterone (DOC) to plasma corticosterone (B) reflected the activity of the enzyme of the B and/or aldosterone pathways, and the ratio of plasma 11-deoxycortisol (S) to plasma cortisol (F) as the activity of the enzyme in the F pathway. In normal subjects, both ratios were significantly lower at 0800-0900 h (Doc to B, .01+/-.004, mean+/-SE, n=10; and S to F, .01+/-.003) than at 2000 h (DOC to B, .028+/-.024 and S to F, .015+/-.005). The plasma levels of DOC, B, S and F were all significantly lower at 2000-2100 h than at 0800-0900 h. In contrast 9 patients with Cushing's syndrome exhibited no diurnal change in the ratios. The ratios increased substantially following dexamethasone or metyrapone administration. A high or low salt diet and an angiotensin infusion produced no significant effect on the ratios. The plasma concentration of all four steroids was increased by more than 50% by an infusion of angiotensin. Four hours after administration of 80 mg of Lasix at 0800 h to 10 normal subjects, the ratios of DOC to B and S to F increased significantly (P less than .02), an effect possibly related to a decreased secretion of ACTH. 1) 11beta-hydroxylase activity of the B and/or aldosterone and F pathways appears to change in parallel with ACTH secretion, and 2) although angiotensin stimulates steroidogenesis of the pathways, it has no apparent effect on 11beta-hydroxylase activity."}
{"id": "PMID:190263", "title": "Studies of the composition and radioreceptor activity of \"big\" and \"little\" human growth hormone.", "content": "Immunoreactive growth hormone (GH) from human pituitary and plasma contains \"big\" (BGH) and \"little\" (LGH) components. BGH itself consists of a \"urea-labile\" form and a \"urea-stable\" form (usBGH). In the present study we determined the amino acid composition of a BGH preparation containing both the urea-labile and urea-stable components and bound it to be indistinguishable from that of LGH. This finding, coupled with observations of others, suggests that urea-labile BGH is a simple LGH dimer and that usBGH is a disulfide dimer. We have prepared LGH, BGH, and usBGH from human pituitary GH, and studied their radioreceptor activity, in relation to their immunoreactivity, in plasma membrane systems from rabbit, rat and human liver and rabbit mammary gland. When 125I-LGH was used as the radioligand, LGH and usBGH caused parallel displacement, usBGH was 60-74% as active as LGH in the animal preparations, while in human liver the two forms were equally active. Three different BGH preparations studied in the animal systems were 26-33% as active as LGH. The receptor activity of these BGH preparations was greater than expected from their usBGH content, suggesting that urea-labile BGH also binds to the LGH receptor. When 125I-usBGH was employed as radioligand, we found that in the presence of 2,000 ng/ml of LGH, which caused maximal displacement of 125I-usBGH, the addition of 2 ng/ml of usBGH produced additional displacement. This suggested the presence of a receptor specific for usBGH. However, the phenomenon proved to be due to a contaminant in the usBGH preparations which decreased binding of 125I-usBGH. BGH containing a substantial fraction of usBGH, and \"freeze-stable\" BGH which is probably identical with usBGH, both failed to displace 125I-usBGH in the presence of 2,000 ng/ml LGH. These observations rule against the existence of a specific receptor for usBGH.", "contents": "Studies of the composition and radioreceptor activity of \"big\" and \"little\" human growth hormone. Immunoreactive growth hormone (GH) from human pituitary and plasma contains \"big\" (BGH) and \"little\" (LGH) components. BGH itself consists of a \"urea-labile\" form and a \"urea-stable\" form (usBGH). In the present study we determined the amino acid composition of a BGH preparation containing both the urea-labile and urea-stable components and bound it to be indistinguishable from that of LGH. This finding, coupled with observations of others, suggests that urea-labile BGH is a simple LGH dimer and that usBGH is a disulfide dimer. We have prepared LGH, BGH, and usBGH from human pituitary GH, and studied their radioreceptor activity, in relation to their immunoreactivity, in plasma membrane systems from rabbit, rat and human liver and rabbit mammary gland. When 125I-LGH was used as the radioligand, LGH and usBGH caused parallel displacement, usBGH was 60-74% as active as LGH in the animal preparations, while in human liver the two forms were equally active. Three different BGH preparations studied in the animal systems were 26-33% as active as LGH. The receptor activity of these BGH preparations was greater than expected from their usBGH content, suggesting that urea-labile BGH also binds to the LGH receptor. When 125I-usBGH was employed as radioligand, we found that in the presence of 2,000 ng/ml of LGH, which caused maximal displacement of 125I-usBGH, the addition of 2 ng/ml of usBGH produced additional displacement. This suggested the presence of a receptor specific for usBGH. However, the phenomenon proved to be due to a contaminant in the usBGH preparations which decreased binding of 125I-usBGH. BGH containing a substantial fraction of usBGH, and \"freeze-stable\" BGH which is probably identical with usBGH, both failed to displace 125I-usBGH in the presence of 2,000 ng/ml LGH. These observations rule against the existence of a specific receptor for usBGH."}
{"id": "PMID:190264", "title": "Urinary excretion of cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-guanosine monophosphate during and after pregnancy.", "content": "Urinary cyclic AMP and cyclic GMP excretions were measured in 24-h urine specimens obtained from 89 women at various times during their normal uncomplicated intrauterine pregnancies and from 49 women at various times after the births of their normal healthy infants. Cyclic AMP excretion increased steadily from the beginning of the second trimester or earlier until late in the third trimester, reaching a peak excretion approximately 40% greater than that of normal nonpregnant women. The cyclic AMP excretion dropped abruptly by the first day after parturition to levels which were not significant different from those of normal non-pregnant women. In contrast, cyclic GMP excretion increased rapidly during the first trimester and remained relatively constant during the remainder of the pregnancy, reaching a peak excretion of about 140% greater than that of normal nonpregnant women. Furthermore, it decreased slowly toward normal levels, but was still significantly elevated six weeks after parturition. The factors responsible for the increased excretion of cyclic AMP during pregnancy and for the increased cyclic GMP during and after pregnancy are not known.", "contents": "Urinary excretion of cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-guanosine monophosphate during and after pregnancy. Urinary cyclic AMP and cyclic GMP excretions were measured in 24-h urine specimens obtained from 89 women at various times during their normal uncomplicated intrauterine pregnancies and from 49 women at various times after the births of their normal healthy infants. Cyclic AMP excretion increased steadily from the beginning of the second trimester or earlier until late in the third trimester, reaching a peak excretion approximately 40% greater than that of normal nonpregnant women. The cyclic AMP excretion dropped abruptly by the first day after parturition to levels which were not significant different from those of normal non-pregnant women. In contrast, cyclic GMP excretion increased rapidly during the first trimester and remained relatively constant during the remainder of the pregnancy, reaching a peak excretion of about 140% greater than that of normal nonpregnant women. Furthermore, it decreased slowly toward normal levels, but was still significantly elevated six weeks after parturition. The factors responsible for the increased excretion of cyclic AMP during pregnancy and for the increased cyclic GMP during and after pregnancy are not known."}
{"id": "PMID:190265", "title": "Effects of ionophore A23187 on base-line and vasopressin-stimulated sodium transport in the toad bladder.", "content": "The cation specific ionophore A23187 (Io) is a useful tool for studying the role of intracellular Ca++ (Ca++)i in physiologic processes. The present studies explore the role of (Ca++)i on Na transport in the toad bladder. Scraped bladder cells exposed to 1 muM Io for 60 min took up 100% more 45Ca than control cells. Io, 1 muM, added to the serosal side of bladders incubated in standard Ringers containing 2.5 mM Ca++ inhibited short circuit current (SCC) values by a mean of 30% at 60 min and 50% at 90 min. Io did not inhibit SCC significantly in bladders incubated in Ringers containing 0.2 mM Ca++. These data indicate that the effects of Io on SCC depend on the levels of external Ca++ and suggest that entry of Ca++ into cells mediates the inhibition of base-line SCC. PReincubation of the bladders with either lanthanum chloride or pentobarbital prevented the increased 45Ca uptake produced by ionophore as well as theinhibition of SCC caused by the antibiotic. Vasopressin, antidiuretic hormone (ADH). 10 MU/ml, increased peak SCC by 247% in bladders preincubated for 1 h in Ringers with 2.5 mM Ca++ and 1 muM Io and by 318% in control bladders (P less than 0.01). Bladders exposed to 1 muM Io in Ringers with 0.2 mM Ca++ had an increase in SCC after ADH comparable to that observed in controls. Since the effects of ADH on SCC are mediated by cyclic AMP, we tested the effects of Io on cAMP production by scraped toad bladder cells. ADH increased cAMP from 8 to 30 pmol/mg protein in controls but it did not increase cAMP over base-line values in the presence of Io when the Ringers contained 2.5 mM Ca++. Io did not inhibit cAMP production in response to ADH when the Ca++ in the Ringers was 0.2 mM. The results indicate that Io inhibits baseline and ADH stimulated SCC by increasing (Ca++)i or Ca++ bound to the cell membrane. It is suggested that: ()( (Ca++)i or membrane-bound Ca++ plays a key role in base-line and ADH stimulated Na transport in the toad bladder; (2) inhibition of ADH stimulated SCC may be due inpart to decreased cAMP generation in response to ADH when (Ca++)i or membrane-bound Ca++ levels are increased.", "contents": "Effects of ionophore A23187 on base-line and vasopressin-stimulated sodium transport in the toad bladder. The cation specific ionophore A23187 (Io) is a useful tool for studying the role of intracellular Ca++ (Ca++)i in physiologic processes. The present studies explore the role of (Ca++)i on Na transport in the toad bladder. Scraped bladder cells exposed to 1 muM Io for 60 min took up 100% more 45Ca than control cells. Io, 1 muM, added to the serosal side of bladders incubated in standard Ringers containing 2.5 mM Ca++ inhibited short circuit current (SCC) values by a mean of 30% at 60 min and 50% at 90 min. Io did not inhibit SCC significantly in bladders incubated in Ringers containing 0.2 mM Ca++. These data indicate that the effects of Io on SCC depend on the levels of external Ca++ and suggest that entry of Ca++ into cells mediates the inhibition of base-line SCC. PReincubation of the bladders with either lanthanum chloride or pentobarbital prevented the increased 45Ca uptake produced by ionophore as well as theinhibition of SCC caused by the antibiotic. Vasopressin, antidiuretic hormone (ADH). 10 MU/ml, increased peak SCC by 247% in bladders preincubated for 1 h in Ringers with 2.5 mM Ca++ and 1 muM Io and by 318% in control bladders (P less than 0.01). Bladders exposed to 1 muM Io in Ringers with 0.2 mM Ca++ had an increase in SCC after ADH comparable to that observed in controls. Since the effects of ADH on SCC are mediated by cyclic AMP, we tested the effects of Io on cAMP production by scraped toad bladder cells. ADH increased cAMP from 8 to 30 pmol/mg protein in controls but it did not increase cAMP over base-line values in the presence of Io when the Ringers contained 2.5 mM Ca++. Io did not inhibit cAMP production in response to ADH when the Ca++ in the Ringers was 0.2 mM. The results indicate that Io inhibits baseline and ADH stimulated SCC by increasing (Ca++)i or Ca++ bound to the cell membrane. It is suggested that: ()( (Ca++)i or membrane-bound Ca++ plays a key role in base-line and ADH stimulated Na transport in the toad bladder; (2) inhibition of ADH stimulated SCC may be due inpart to decreased cAMP generation in response to ADH when (Ca++)i or membrane-bound Ca++ levels are increased."}
{"id": "PMID:190266", "title": "Enzymatic basis for bioenergetic differences of alveolar versus peritoneal macrophages and enzyme regulation by molecular O2.", "content": "Alveolar macrophages (AM) and peritoneal macrophages (PM) originate from common precursor cells, but function in different O2 environments. In the present studies, the impact of different O2 tensions on cell metabolism has been quantitatively determined, an enzymatic basis for these differences established, and a mechanism which regulates enzymatic differences demonstrated. O2 consumption and lactate production were compared in rabbit AM and PM in air and nitrogen. In air, AM demonstrate significantly greater O2 utilization. In nitrogen, (where glycolysis is the major source of energy provision) lactate production is two- to threefold greater in the PM. A comparison of several enzymes of energy metabolism in AM and PM indicate that one basis for the differences in cell energetics is a difference in activity of key enzymes of both the oxidative phosphorlyative and the glycolytic sequences. Exposure of cultivated AM to hypoxic conditions results in changes in the activity of these enzymes such that the AM closely resembles the PM. A key enzyme in oxidative phosphorylation (cytochrome oxidase) shows decreased activity and reaches values similar to those found in the PM. A key enzyme in glycolysis (pyruvate kinase) shows increased activity to values resembling those found in the PM. These alterations in enzyme pattern occur in isolated cell systems, suggesting that molecular O2 modifies the intrinsic cellular regulation of some enzymes of energy metabolism. Alterations in O2 tension may lead to alterations of the rate of biosynthesis and (or) the rate of biodegradation of key enzymes involved in oxidative phosphorylation and glycolysis. In turn, the alteration of enzyme patterns leads to a more suitable bioenergetic pattern as a function of O2 availability.", "contents": "Enzymatic basis for bioenergetic differences of alveolar versus peritoneal macrophages and enzyme regulation by molecular O2. Alveolar macrophages (AM) and peritoneal macrophages (PM) originate from common precursor cells, but function in different O2 environments. In the present studies, the impact of different O2 tensions on cell metabolism has been quantitatively determined, an enzymatic basis for these differences established, and a mechanism which regulates enzymatic differences demonstrated. O2 consumption and lactate production were compared in rabbit AM and PM in air and nitrogen. In air, AM demonstrate significantly greater O2 utilization. In nitrogen, (where glycolysis is the major source of energy provision) lactate production is two- to threefold greater in the PM. A comparison of several enzymes of energy metabolism in AM and PM indicate that one basis for the differences in cell energetics is a difference in activity of key enzymes of both the oxidative phosphorlyative and the glycolytic sequences. Exposure of cultivated AM to hypoxic conditions results in changes in the activity of these enzymes such that the AM closely resembles the PM. A key enzyme in oxidative phosphorylation (cytochrome oxidase) shows decreased activity and reaches values similar to those found in the PM. A key enzyme in glycolysis (pyruvate kinase) shows increased activity to values resembling those found in the PM. These alterations in enzyme pattern occur in isolated cell systems, suggesting that molecular O2 modifies the intrinsic cellular regulation of some enzymes of energy metabolism. Alterations in O2 tension may lead to alterations of the rate of biosynthesis and (or) the rate of biodegradation of key enzymes involved in oxidative phosphorylation and glycolysis. In turn, the alteration of enzyme patterns leads to a more suitable bioenergetic pattern as a function of O2 availability."}
{"id": "PMID:190267", "title": "Cyclic adenosine 3',5'-monophosphate inhibits the availability of arachidonate to prostaglandin synthetase in human platelet suspensions.", "content": "When thrombin is added to washed human platelets, one of its actions results in activation of a phospholipase that hydrolyzes arachidonic acid from phospholipids. The arachidonate is converted to the cyclic endoperoxides (prostaglandin G2 and prostaglandin H2) by fatty acid cyclo-oxygenase. These compounds are then converted to thromboxane A2, also called rabbit aorta-contracting substance, by thromboxane synthetase. These labile, pharmacologically active compounds then break down to inactive products including thromboxane B2 and malonaldehyde. Incubation of platelets with either dibutyryl cyclic adenosine 3',5'-monophosphate (dBcAMP) or prostaglandin E1 (PGE1) before thrombin addition blocks the subsequent formation of oxygenated products of arachidonic acid including thromboxane A2, thromboxane B2, and malonaldehyde. In contrast, when arachidonic acid is added directly to platelets, prior incubation with dBcAMP or PGE1 does not inhibit production of the prostaglandins or their metabolites. Thrombin treatment of platelets also blocks the acetylation of cyclo-oxygenase by aspirin since the hydrolyzed arachidonic acid competes with aspirin for the active site on cyclo-oxygenase. Prior treatment of platelets with dBcAMP or PGE1 reverses the thrombin inhibition of the acetylation of cyclo-oxygenase. We conclude that agents which elevate platelet cAMP levels inhibit the hydrolysis of arachidonic acid from platelet phospholipids. We also find that prostaglandin synthesis can be dissociated, in part, from platelet aggregation and release, and that cAMP has separate actions on these processes. Higher thrombin concentrations are required to stimulate prostaglandin synthesis (0.05-2 U/ml) than are required to induce [14C]serotonin release (0.02-0.1 U/ml). Furthermore, dBcAMP and PGE1 both inhibit platelet aggregation induced by either arachidonic acid or prostaglandin H2 without affecting the production of prostaglandin metabolites from these compounds.", "contents": "Cyclic adenosine 3',5'-monophosphate inhibits the availability of arachidonate to prostaglandin synthetase in human platelet suspensions. When thrombin is added to washed human platelets, one of its actions results in activation of a phospholipase that hydrolyzes arachidonic acid from phospholipids. The arachidonate is converted to the cyclic endoperoxides (prostaglandin G2 and prostaglandin H2) by fatty acid cyclo-oxygenase. These compounds are then converted to thromboxane A2, also called rabbit aorta-contracting substance, by thromboxane synthetase. These labile, pharmacologically active compounds then break down to inactive products including thromboxane B2 and malonaldehyde. Incubation of platelets with either dibutyryl cyclic adenosine 3',5'-monophosphate (dBcAMP) or prostaglandin E1 (PGE1) before thrombin addition blocks the subsequent formation of oxygenated products of arachidonic acid including thromboxane A2, thromboxane B2, and malonaldehyde. In contrast, when arachidonic acid is added directly to platelets, prior incubation with dBcAMP or PGE1 does not inhibit production of the prostaglandins or their metabolites. Thrombin treatment of platelets also blocks the acetylation of cyclo-oxygenase by aspirin since the hydrolyzed arachidonic acid competes with aspirin for the active site on cyclo-oxygenase. Prior treatment of platelets with dBcAMP or PGE1 reverses the thrombin inhibition of the acetylation of cyclo-oxygenase. We conclude that agents which elevate platelet cAMP levels inhibit the hydrolysis of arachidonic acid from platelet phospholipids. We also find that prostaglandin synthesis can be dissociated, in part, from platelet aggregation and release, and that cAMP has separate actions on these processes. Higher thrombin concentrations are required to stimulate prostaglandin synthesis (0.05-2 U/ml) than are required to induce [14C]serotonin release (0.02-0.1 U/ml). Furthermore, dBcAMP and PGE1 both inhibit platelet aggregation induced by either arachidonic acid or prostaglandin H2 without affecting the production of prostaglandin metabolites from these compounds."}
{"id": "PMID:190268", "title": "Enhanced activity of hormone-sensitive adenylate cyclase during dietary restriction in the rat: dependence on age and relation to cell size.", "content": "Age-related decreases of hormone-sensitive adenylate cyclase activities of rat fat cell plasma membranes (ghosts) have been recently described. Glucagon-sensitive activity was completely lost between 1 and 6 mo, an interval in which fat cell size increases rapidly, while decreased activation by ACTH was gradual over the entire life span of the animal (24 mo), and epinephrine-sensitive enzyme diminished modestly and only during senescence. In the present studies an attempt was made by restricting food intake to assess the importance of changing cell size in the age-related alterations of hormone-sensitive enzyme activities. Enzyme activities were determined before restriction and at monthly intervals for 3 mo for the unstimulated enzyme (basal) and in the presence of maximally stimulating concentrations of glucagon, ACTH, epinephrine, and fluoride. Activities were calculated per milligram ghost protein or per cell. Restriction of food intake for 3 mo starting at 1 or 12 mo produced fat cells equal in size to those of 5-wk-old animals fed ad lib. In young animals restricted for 1 mo, hormone-stimulated activity expressed as fold increase (stimulated/basal) was not merely maintained as the cells were prevented from enlarging, but was enhanced two to three times over the initial values with all three hormones. With continued restriction epinephrine-sensitive activity remained two times increased. Glucagon and ACTH responses subsequently decreased, but even by 3 mo of restriction, responses to the latter hormones, although declining, were still 1.5-3 times greater than the unrestricted controls, regardless of whether activity was expressed as total activity per milligram ghost protein or per cell, or as fold-increase. In the young animals, basal and fluoride-sensitive activities after a 3-mo restriction were unchanged or had decreased only slightly, depending on the base line used. Dietary restriction of adult animals for 3 mo, in contrast to the results in the young, did not increase total hormone-stimulated activity but rather produced either 0% (per milligram protein) or 25% decrease (per cell) for epinephrine-sensitive enzyme, 25 or 50% decrease of ACTH response, and 40 or 60% decreases of basal- and fluoride-stimulated activities. Expression of activities of restricted adults as fold-increase (stimulate/basal) showed an \"increase of responsiveness\" for all three hormones, but this was a reflection of the marked decrease of basal activity. Nonetheless, the restricted adults showed significant restoration of a small amount of glucagon-sensitive activity (1.8-fold over basal). These results indicate that cell size, per se, is not a dominant factor affecting hormone-responsive adenylate cyclase under conditions of dietary restriction...", "contents": "Enhanced activity of hormone-sensitive adenylate cyclase during dietary restriction in the rat: dependence on age and relation to cell size. Age-related decreases of hormone-sensitive adenylate cyclase activities of rat fat cell plasma membranes (ghosts) have been recently described. Glucagon-sensitive activity was completely lost between 1 and 6 mo, an interval in which fat cell size increases rapidly, while decreased activation by ACTH was gradual over the entire life span of the animal (24 mo), and epinephrine-sensitive enzyme diminished modestly and only during senescence. In the present studies an attempt was made by restricting food intake to assess the importance of changing cell size in the age-related alterations of hormone-sensitive enzyme activities. Enzyme activities were determined before restriction and at monthly intervals for 3 mo for the unstimulated enzyme (basal) and in the presence of maximally stimulating concentrations of glucagon, ACTH, epinephrine, and fluoride. Activities were calculated per milligram ghost protein or per cell. Restriction of food intake for 3 mo starting at 1 or 12 mo produced fat cells equal in size to those of 5-wk-old animals fed ad lib. In young animals restricted for 1 mo, hormone-stimulated activity expressed as fold increase (stimulated/basal) was not merely maintained as the cells were prevented from enlarging, but was enhanced two to three times over the initial values with all three hormones. With continued restriction epinephrine-sensitive activity remained two times increased. Glucagon and ACTH responses subsequently decreased, but even by 3 mo of restriction, responses to the latter hormones, although declining, were still 1.5-3 times greater than the unrestricted controls, regardless of whether activity was expressed as total activity per milligram ghost protein or per cell, or as fold-increase. In the young animals, basal and fluoride-sensitive activities after a 3-mo restriction were unchanged or had decreased only slightly, depending on the base line used. Dietary restriction of adult animals for 3 mo, in contrast to the results in the young, did not increase total hormone-stimulated activity but rather produced either 0% (per milligram protein) or 25% decrease (per cell) for epinephrine-sensitive enzyme, 25 or 50% decrease of ACTH response, and 40 or 60% decreases of basal- and fluoride-stimulated activities. Expression of activities of restricted adults as fold-increase (stimulate/basal) showed an \"increase of responsiveness\" for all three hormones, but this was a reflection of the marked decrease of basal activity. Nonetheless, the restricted adults showed significant restoration of a small amount of glucagon-sensitive activity (1.8-fold over basal). These results indicate that cell size, per se, is not a dominant factor affecting hormone-responsive adenylate cyclase under conditions of dietary restriction..."}
{"id": "PMID:190269", "title": "Stimulation of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme by L-triiodothyronine. Characteristics of the response with specific nuclear thyroid hormone binding sites fully saturated.", "content": "Experiments were designed to analyze the relationship of a single i.v. dose of triiodothyronine (T3), the level of plasma and hepatic nuclear T3 attained, and the tissue response as reflected in increased activity of hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytosol \"malic enzyme\" (ME). These studied were carried out in euthyroid rats by varying the dose of T3 injected and the time at which the animals were killed and the enzyme levels measured. The plasma T3 concentration was determined and the fraction of nuclear sites occupied at any time t was calculated from the known plasma:nuclear relationship. As a first step, the analysis was confined to the limiting situation in which all nuclear sites were effectively saturated. The following additional information was required and obtained: A proportional relationship between the half-neutralizing volume of a specific antiserum to malic enzyme and the activity of malic enzyme was established, thus confirming previous reports that the increase in enzyme activity induced by T3 is due to increased enzyme mass. The absolute refractory period immediately after i.v. injection of T3, during which no enzyme response could be detected, was determined. This was shown to be 13.4 h for alpha-GPD and 8.2 h for ME. Lastly, the t1/2 of the enzyme decay after pulse injection of T3 was measured. This was similar for both enzymes, 2.8+/-0.6 (SD) days for alpha-GPD and 2.7+/-0.6 (SD) days for ME. The results of these studies indicated that the extent of hepatic response appears limited by full occupancy of a set of intracellular receptor sites by T3 which is in rapid equilibrium with the plasma hormone pool. The kinetic properties of the receptors, as functionally defined in these studies, resemble those associated with the recently described specific nuclear T3 sites. These data per se are thus compatible with but do not prove a nuclear site of initiation of hormone effect. Thye do allow the development of an internally consistent mathematical model which permits prediction of enzyme response when the receptor sites are fully occupied for a given length of time after the i.v. injection of hormone. A separate series of studies was carried out in thyroidectomized rats. The response characteristics of alpha-GPD were similar to those observed in euthyroid animals. In contrast, however, the early response of ME to pulse injections of T3 was very much reduced in hypothyroid animals as compared to euthryoid animals in which nuclear sites were saturated for comparable periods. These findings raise the possibility that a factor required for the induction of malic enzyme but not alpha-GPD is deficient in the hypothyroid state.", "contents": "Stimulation of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme by L-triiodothyronine. Characteristics of the response with specific nuclear thyroid hormone binding sites fully saturated. Experiments were designed to analyze the relationship of a single i.v. dose of triiodothyronine (T3), the level of plasma and hepatic nuclear T3 attained, and the tissue response as reflected in increased activity of hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytosol \"malic enzyme\" (ME). These studied were carried out in euthyroid rats by varying the dose of T3 injected and the time at which the animals were killed and the enzyme levels measured. The plasma T3 concentration was determined and the fraction of nuclear sites occupied at any time t was calculated from the known plasma:nuclear relationship. As a first step, the analysis was confined to the limiting situation in which all nuclear sites were effectively saturated. The following additional information was required and obtained: A proportional relationship between the half-neutralizing volume of a specific antiserum to malic enzyme and the activity of malic enzyme was established, thus confirming previous reports that the increase in enzyme activity induced by T3 is due to increased enzyme mass. The absolute refractory period immediately after i.v. injection of T3, during which no enzyme response could be detected, was determined. This was shown to be 13.4 h for alpha-GPD and 8.2 h for ME. Lastly, the t1/2 of the enzyme decay after pulse injection of T3 was measured. This was similar for both enzymes, 2.8+/-0.6 (SD) days for alpha-GPD and 2.7+/-0.6 (SD) days for ME. The results of these studies indicated that the extent of hepatic response appears limited by full occupancy of a set of intracellular receptor sites by T3 which is in rapid equilibrium with the plasma hormone pool. The kinetic properties of the receptors, as functionally defined in these studies, resemble those associated with the recently described specific nuclear T3 sites. These data per se are thus compatible with but do not prove a nuclear site of initiation of hormone effect. Thye do allow the development of an internally consistent mathematical model which permits prediction of enzyme response when the receptor sites are fully occupied for a given length of time after the i.v. injection of hormone. A separate series of studies was carried out in thyroidectomized rats. The response characteristics of alpha-GPD were similar to those observed in euthyroid animals. In contrast, however, the early response of ME to pulse injections of T3 was very much reduced in hypothyroid animals as compared to euthryoid animals in which nuclear sites were saturated for comparable periods. These findings raise the possibility that a factor required for the induction of malic enzyme but not alpha-GPD is deficient in the hypothyroid state."}
{"id": "PMID:190270", "title": "Angiotensin antagonists with increased specificity for the renal vasculature.", "content": "This study was designed to ascertain whether renal vascular angiotensin receptors differ from other systemic angiotensin receptors and whether, on that basis, antagonists with greater specificity for the renal vasculature can be defined. Femoral and renal blood flow and their responses to angiotensin II (AII) and its heptapeptide analogue, 1-des Asp AII (AIII), were measured with an electromagnetic flowmeter in 26 dogs. For the kidney, the threshold doses of AII and AIII were identical (2.5+/-0.27 vs. 2.3+/-0.35 pmol/100 ml renal blood flow, with similar dose-response curves. In contrast, AII had a greater pressor effect (P less than 0.001) and produced more femoral vasoconstriction (P less than 0.001) than AIII. All four antagonists studied (1-Sar, 8-Ala AII [P113]; 8-Ala AII; 1-des Asp, 8-Ala AII; 1-des Asp, 8-Ile AII) induced parallel shifts in the renal blood flow response to AII and AIII. P113 induced greater blockade than 8-Ala AII (P less than 0.001) which, in turn, was more effective than 1-des Asp, 8-Ala AII (P less than 0.001). 1-des Asp, 8-Ile AII was as effective as P113. Each analogue induced an identical inhibition of the renal vascular response to AII and AIII. In addition, AII and AIII induced cross-tachyphylaxis. All lines of evidence suggested that AII and AIII act on a single receptor in the kidney, which differs at least functionally from other systemic vascular receptors. The possibility that heptapeptide analogues represent angiotensin antagonists with greater specificity for the renal vasculature was pursued in a model in which the renin-angiotensin system is activated. Acute, partial thoracic inferior vena caval occlusion was induced in an additional 16 dogs. P113 induced progressive, dose-related hypotension and a limited increase in renal blood flow in this model. The 1-des Asp, 8-Ile AII analogue, conversely, induced a consistent, larger, dose-related renal blood flow increase, with significantly less hypotension over a wide dose range. We conclude that the renal vascular receptor differs sufficiently from systemic angiotensin receptors that heptapeptide analogues of AII will be useful in exploring angiotensin's role in states characterized by disordered renal perfusion and function.", "contents": "Angiotensin antagonists with increased specificity for the renal vasculature. This study was designed to ascertain whether renal vascular angiotensin receptors differ from other systemic angiotensin receptors and whether, on that basis, antagonists with greater specificity for the renal vasculature can be defined. Femoral and renal blood flow and their responses to angiotensin II (AII) and its heptapeptide analogue, 1-des Asp AII (AIII), were measured with an electromagnetic flowmeter in 26 dogs. For the kidney, the threshold doses of AII and AIII were identical (2.5+/-0.27 vs. 2.3+/-0.35 pmol/100 ml renal blood flow, with similar dose-response curves. In contrast, AII had a greater pressor effect (P less than 0.001) and produced more femoral vasoconstriction (P less than 0.001) than AIII. All four antagonists studied (1-Sar, 8-Ala AII [P113]; 8-Ala AII; 1-des Asp, 8-Ala AII; 1-des Asp, 8-Ile AII) induced parallel shifts in the renal blood flow response to AII and AIII. P113 induced greater blockade than 8-Ala AII (P less than 0.001) which, in turn, was more effective than 1-des Asp, 8-Ala AII (P less than 0.001). 1-des Asp, 8-Ile AII was as effective as P113. Each analogue induced an identical inhibition of the renal vascular response to AII and AIII. In addition, AII and AIII induced cross-tachyphylaxis. All lines of evidence suggested that AII and AIII act on a single receptor in the kidney, which differs at least functionally from other systemic vascular receptors. The possibility that heptapeptide analogues represent angiotensin antagonists with greater specificity for the renal vasculature was pursued in a model in which the renin-angiotensin system is activated. Acute, partial thoracic inferior vena caval occlusion was induced in an additional 16 dogs. P113 induced progressive, dose-related hypotension and a limited increase in renal blood flow in this model. The 1-des Asp, 8-Ile AII analogue, conversely, induced a consistent, larger, dose-related renal blood flow increase, with significantly less hypotension over a wide dose range. We conclude that the renal vascular receptor differs sufficiently from systemic angiotensin receptors that heptapeptide analogues of AII will be useful in exploring angiotensin's role in states characterized by disordered renal perfusion and function."}
{"id": "PMID:190271", "title": "Leukocyte procoagulant activity: enhancement of production in vitro by IgG and antigen-antibody complexes.", "content": "In a variety of immunologic diseases, fibrin-fibrinogen and immune complexes deposit in areas of tissue damage. However, the mechanisms which initiate fibrin-fibrinogen deposition have not been clarified. We find that the procoagulant activity of human leukocytes is markedly increased after incubation with immunoglobulin and immune complexes. This procoagulant activity is evident after 4-24 h incubation in the presence of as little as 0.1 mg/ml of autologous, isologous, or heterologous IgG. At least three of the four subclasses of IgG myeloma proteins are effective. Experiments with purified rabbit and rat antibodies demonstrate that enhancement of procoagulant activity is significantly greater with soluble antigen-antibody complexes than with immunoglobulin alone. In contrast, insoluble complexes are less affective than immunoglobulin alone. Artifacts due to endotoxin contamination of the IgG preparations were excluded on the basis of the differential sensitivities of immunoglobulin and endotoxin to heat and polymyxin B. Evidence is also presented which shows that enhancement of procoagulant activity involves the production, rather than a simple release, of leukocyte procoagulant activity in vitro.", "contents": "Leukocyte procoagulant activity: enhancement of production in vitro by IgG and antigen-antibody complexes. In a variety of immunologic diseases, fibrin-fibrinogen and immune complexes deposit in areas of tissue damage. However, the mechanisms which initiate fibrin-fibrinogen deposition have not been clarified. We find that the procoagulant activity of human leukocytes is markedly increased after incubation with immunoglobulin and immune complexes. This procoagulant activity is evident after 4-24 h incubation in the presence of as little as 0.1 mg/ml of autologous, isologous, or heterologous IgG. At least three of the four subclasses of IgG myeloma proteins are effective. Experiments with purified rabbit and rat antibodies demonstrate that enhancement of procoagulant activity is significantly greater with soluble antigen-antibody complexes than with immunoglobulin alone. In contrast, insoluble complexes are less affective than immunoglobulin alone. Artifacts due to endotoxin contamination of the IgG preparations were excluded on the basis of the differential sensitivities of immunoglobulin and endotoxin to heat and polymyxin B. Evidence is also presented which shows that enhancement of procoagulant activity involves the production, rather than a simple release, of leukocyte procoagulant activity in vitro."}
{"id": "PMID:190272", "title": "The lipoprotein abnormality in Tangier disease: quantitation of A apoproteins.", "content": "In this study we have determined by radioimmunoassay and double immunoelectrophoresis the total quantities and distributions of A apoproteins in three adult patients affected with Tangier disease (hereditary alpha-lipoprotein deficiency). Compared with normal plasma, the total quantities of apoproteins A-I and A-II in Tangier plasma were determined to be less than 1% and 5-7%, respectively. In Tangier patients, approximately 90% of the apoprotein A-I sedimented when ultracentrifugations of plasma were carried out at density 1.21 g/ml KBr. By contrast, more than 95% of the apoprotein A-II floated under those conditions. In normal plasma, approximately 90% of both apoproteins A-I and A-II is found in the 1.063-1.21-g/ml KBr density fraction. These findings suggest that complete dissociation of A apoproteins occurs in Tangier plasma. This dissociation of apoproteins was confirmed by double immunoelectrophoresis with monospecific antisera. Immunochemical and electrophoretic experiments did not provide evidence for a structural abnormality of apoprotein A-I in these patients, The results taken together strongly suggest that normal high-density lipoproteins are absent from Tangier plasma.", "contents": "The lipoprotein abnormality in Tangier disease: quantitation of A apoproteins. In this study we have determined by radioimmunoassay and double immunoelectrophoresis the total quantities and distributions of A apoproteins in three adult patients affected with Tangier disease (hereditary alpha-lipoprotein deficiency). Compared with normal plasma, the total quantities of apoproteins A-I and A-II in Tangier plasma were determined to be less than 1% and 5-7%, respectively. In Tangier patients, approximately 90% of the apoprotein A-I sedimented when ultracentrifugations of plasma were carried out at density 1.21 g/ml KBr. By contrast, more than 95% of the apoprotein A-II floated under those conditions. In normal plasma, approximately 90% of both apoproteins A-I and A-II is found in the 1.063-1.21-g/ml KBr density fraction. These findings suggest that complete dissociation of A apoproteins occurs in Tangier plasma. This dissociation of apoproteins was confirmed by double immunoelectrophoresis with monospecific antisera. Immunochemical and electrophoretic experiments did not provide evidence for a structural abnormality of apoprotein A-I in these patients, The results taken together strongly suggest that normal high-density lipoproteins are absent from Tangier plasma."}
{"id": "PMID:190273", "title": "Detection of pregnancy specific beta1-glycoprotein in formalin-fixed tissues.", "content": "Using an enzyme-bridge immunoperoxidase method, pregnancy specific beta1-glycoprotein (PSbetaG) has been demonstrated in the cytoplasm of the trophoblast in several formalin-fixed tissues, namely, implantation sites of ovum, normal placentae, hydatidiform moles, invasive moles, and choriocarcinomata of uterus and testis. It is suggested that this technique may prove helpful in the detection of choriocarcinomatous elements in malignant tumours.", "contents": "Detection of pregnancy specific beta1-glycoprotein in formalin-fixed tissues. Using an enzyme-bridge immunoperoxidase method, pregnancy specific beta1-glycoprotein (PSbetaG) has been demonstrated in the cytoplasm of the trophoblast in several formalin-fixed tissues, namely, implantation sites of ovum, normal placentae, hydatidiform moles, invasive moles, and choriocarcinomata of uterus and testis. It is suggested that this technique may prove helpful in the detection of choriocarcinomatous elements in malignant tumours."}
{"id": "PMID:190274", "title": "Relay cell classes in the lateral geniculate nucleus of the cat and the effects of visual deprivation.", "content": "This study presents evidence that the X- and Y-cells described physiologically in the A laminae of the cat's dorsal lateral geniculate nucleus (LGN) are two morphologically distinct cell types recognizable in Golgi preparations. It is shown firstly that the three cell types seen in Golgi preparations of the A laminae (large and medium-sized principal cells and small interneurons-types 1,2 and 3 in the classification of Guillery, '66) may be identified in 1-mum Epon sections of osmicated material. While cell-diameter histograms prepared from serial 1-mum sections show a unimodal distribution of cell sizes, three populations can be distinguished if attention is paid to the presence or absence of large cytoplasmic inclusions (laminar bodies). These three populations consist of large cells lacking laminar bodies (Class I), medium-sized cells possessing laminar bodies (Class II) and small cells lacking them (Class III). That these three classes correspond to the three morphological types has been shown by (i) size comparisons, and (ii) direct demonstration of laminar bodies in the Golgi-impregnated cell bodies of Guillery's type 2 cells. Histograms prepared in this way for samples taken at various positions in the LGN show that the numbers of class II cells decline from the representation of the area centralis to the monocular segment. This decline is compensated by a corresponding rise in the numbers of class I cells. This pattern of distribution is similar to the physiologically observed distribution of X- and Y-cells, indicating that X-cells are likely to be class II cells and Y-cells class I cells. The cortical projections of the various cell types have been examined by the horseradish peroxidase method. Class II cells project to area 17 only. Most class I cells also project to area 17 only, but a few very large class I cells project to area 18. From our results, it appears that very few if any cells in the A laminae have branching axons supplying both 17 and 18. The class III cells do not project to the visual cortex, a finding consistent with their identification as interneurons. Class I and II cells are also found in lamina C and in the MIN. In both these regions there is a predominance of very large class I cells, which project to area 18. Laminae Cl-C3 contain small cells lacking laminar bodies. These cells may project to both areas 17 and 18 with branching axons. They are likely to correspond to Guillery's type 4 cells (small relay cells confined to the C laminae) and to the physiologically described W-cells. Long-term monocular deprivation causes cell shrinkage which is much more severe for class I than for class II cells. There is in addition a decrease in the relative numbers of class I cells. This decrease is found in binocular deprivation also. These observations provide an anatomical basis for the reported loss of Y-cells from deprived laminae of the LGN. It is suggested that the effects of deprivation on Y-cells may be accounted for in terms of competition for synaptic space.", "contents": "Relay cell classes in the lateral geniculate nucleus of the cat and the effects of visual deprivation. This study presents evidence that the X- and Y-cells described physiologically in the A laminae of the cat's dorsal lateral geniculate nucleus (LGN) are two morphologically distinct cell types recognizable in Golgi preparations. It is shown firstly that the three cell types seen in Golgi preparations of the A laminae (large and medium-sized principal cells and small interneurons-types 1,2 and 3 in the classification of Guillery, '66) may be identified in 1-mum Epon sections of osmicated material. While cell-diameter histograms prepared from serial 1-mum sections show a unimodal distribution of cell sizes, three populations can be distinguished if attention is paid to the presence or absence of large cytoplasmic inclusions (laminar bodies). These three populations consist of large cells lacking laminar bodies (Class I), medium-sized cells possessing laminar bodies (Class II) and small cells lacking them (Class III). That these three classes correspond to the three morphological types has been shown by (i) size comparisons, and (ii) direct demonstration of laminar bodies in the Golgi-impregnated cell bodies of Guillery's type 2 cells. Histograms prepared in this way for samples taken at various positions in the LGN show that the numbers of class II cells decline from the representation of the area centralis to the monocular segment. This decline is compensated by a corresponding rise in the numbers of class I cells. This pattern of distribution is similar to the physiologically observed distribution of X- and Y-cells, indicating that X-cells are likely to be class II cells and Y-cells class I cells. The cortical projections of the various cell types have been examined by the horseradish peroxidase method. Class II cells project to area 17 only. Most class I cells also project to area 17 only, but a few very large class I cells project to area 18. From our results, it appears that very few if any cells in the A laminae have branching axons supplying both 17 and 18. The class III cells do not project to the visual cortex, a finding consistent with their identification as interneurons. Class I and II cells are also found in lamina C and in the MIN. In both these regions there is a predominance of very large class I cells, which project to area 18. Laminae Cl-C3 contain small cells lacking laminar bodies. These cells may project to both areas 17 and 18 with branching axons. They are likely to correspond to Guillery's type 4 cells (small relay cells confined to the C laminae) and to the physiologically described W-cells. Long-term monocular deprivation causes cell shrinkage which is much more severe for class I than for class II cells. There is in addition a decrease in the relative numbers of class I cells. This decrease is found in binocular deprivation also. These observations provide an anatomical basis for the reported loss of Y-cells from deprived laminae of the LGN. It is suggested that the effects of deprivation on Y-cells may be accounted for in terms of competition for synaptic space."}
{"id": "PMID:190279", "title": "Probable role of viruses in calfhood diseases.", "content": "Bovine enteroviruses, bovine viral diarrhea virus, rotavirus (formerly called reovirus-like agent), coronavirus-like agent, bovine adenovirus, and bovine parainfluenza-3 virus have been isolated from calves suffering from neonatal disease. The experimental disease produced by these viruses is not necessarily severe or fatal, but under farm and ranch conditions, each probably serves as an added to mortality from neonatal disease. After initial losses following the introduction of a virus into a herd, the subsequent losses will be limited because the cow will produce antibodies to protect the fetus during gestation. Antibodies will also be concentrated in colostrum to protect the calf at birth. However, colostrum must be fed immediately after birth, before the calf becomes infected.", "contents": "Probable role of viruses in calfhood diseases. Bovine enteroviruses, bovine viral diarrhea virus, rotavirus (formerly called reovirus-like agent), coronavirus-like agent, bovine adenovirus, and bovine parainfluenza-3 virus have been isolated from calves suffering from neonatal disease. The experimental disease produced by these viruses is not necessarily severe or fatal, but under farm and ranch conditions, each probably serves as an added to mortality from neonatal disease. After initial losses following the introduction of a virus into a herd, the subsequent losses will be limited because the cow will produce antibodies to protect the fetus during gestation. Antibodies will also be concentrated in colostrum to protect the calf at birth. However, colostrum must be fed immediately after birth, before the calf becomes infected."}
{"id": "PMID:190276", "title": "Inhibition of G2 phase in unsynchronized HELA cells: synergism between adenosine 3':5'-monophosphate analogues and phosphodiesterase inhibitors.", "content": "The involvement of cyclic nucleotides of G2 phase of the cell cycle was reexamined in unsynchronized HeLa cells. Two methods were employed to determine if cell cycle traverse was affected by chemical agents. The first method analyzed cell density changes a relatively early times after drug treatment. The second method entailed selection of a cohort of \"tagged\" G2 cells and analysis of the progress of these cells into mitosis. Synergism between the effects of low levels of cyclic nucleotide analogues and phosphodiesterase inhibitors was used as a criterion for the specificity of an agent's action. Using both methods of cell cycle analysis, synergistic inhibition of cell division was observed with adenosine 3':5'-monophosphate analogues. No synergism was observed with various control compounds or with guanosine 3':5'-monophosphate analogues. The results are interpreted to indicate that adenosine 3':5'-monophosphate exerts an inhibitory action in G2 phase of the cell cycle.", "contents": "Inhibition of G2 phase in unsynchronized HELA cells: synergism between adenosine 3':5'-monophosphate analogues and phosphodiesterase inhibitors. The involvement of cyclic nucleotides of G2 phase of the cell cycle was reexamined in unsynchronized HeLa cells. Two methods were employed to determine if cell cycle traverse was affected by chemical agents. The first method analyzed cell density changes a relatively early times after drug treatment. The second method entailed selection of a cohort of \"tagged\" G2 cells and analysis of the progress of these cells into mitosis. Synergism between the effects of low levels of cyclic nucleotide analogues and phosphodiesterase inhibitors was used as a criterion for the specificity of an agent's action. Using both methods of cell cycle analysis, synergistic inhibition of cell division was observed with adenosine 3':5'-monophosphate analogues. No synergism was observed with various control compounds or with guanosine 3':5'-monophosphate analogues. The results are interpreted to indicate that adenosine 3':5'-monophosphate exerts an inhibitory action in G2 phase of the cell cycle."}
{"id": "PMID:190280", "title": "Proposed calfhood immunization program for the commercial dairy herd.", "content": "Immunization programs never will usurp the central role of sound management practices and good nutrition in the disease prevention program of the commercial dairy operation. However, certain immunizations against diseases such as brucellosis, leptospirosis, and clostridial infections should be routine. Other diseases such as infectious bovine rhinotracheitis, bovine virus diarrhea, parainfluenza-3, colibacillosis, and pasteurellosis should be considered if it can be determined that the herd is infected chronically. The present knowledge of other disease conditions, vaccine effectiveness and safety makes the use of vaccines for other diseases of questionable value.", "contents": "Proposed calfhood immunization program for the commercial dairy herd. Immunization programs never will usurp the central role of sound management practices and good nutrition in the disease prevention program of the commercial dairy operation. However, certain immunizations against diseases such as brucellosis, leptospirosis, and clostridial infections should be routine. Other diseases such as infectious bovine rhinotracheitis, bovine virus diarrhea, parainfluenza-3, colibacillosis, and pasteurellosis should be considered if it can be determined that the herd is infected chronically. The present knowledge of other disease conditions, vaccine effectiveness and safety makes the use of vaccines for other diseases of questionable value."}
{"id": "PMID:190277", "title": "Cyclic 3',5'-adenosine monophosphate phosphodiesterase in the thymus of normal and leukemic mice.", "content": "Changes in the cyclic AMP phosphodiesterase of the thymus were observed during leukemogenesis in the AKR mouse. Upon maturation, activity at 1.0 muM and 100 muM cyclic AMP concentrations decreased in both the AKR mouse and normal Swiss mice. The thymus of the leukemic mouse had sharply higher phosphodiesterase activity. Much of the phosphodiesterase activity of normal and leukemic mice was associated with particulate fractions, and, as indicated by marker enzymes for particulate components, the high affinity phosphodiesterase was enriched in a fraction containing plasma membranes.", "contents": "Cyclic 3',5'-adenosine monophosphate phosphodiesterase in the thymus of normal and leukemic mice. Changes in the cyclic AMP phosphodiesterase of the thymus were observed during leukemogenesis in the AKR mouse. Upon maturation, activity at 1.0 muM and 100 muM cyclic AMP concentrations decreased in both the AKR mouse and normal Swiss mice. The thymus of the leukemic mouse had sharply higher phosphodiesterase activity. Much of the phosphodiesterase activity of normal and leukemic mice was associated with particulate fractions, and, as indicated by marker enzymes for particulate components, the high affinity phosphodiesterase was enriched in a fraction containing plasma membranes."}
{"id": "PMID:190278", "title": "Regulation of protein kinase in rat pineal: increased Vmax in supersensitive glands.", "content": "Protein kinase activity was examined in supernatants from super-sensitive and subsensitive rat pineal glands both in the presence and absence of added cAMP. After a 20 min exposure to 1-isoproterenol, in vivo or in organ culture, supersensitive pineals displayed a greater decrease in protein kinase activity (in the absence of added cAMP) than did subsensitive glands. Furthermore, exposure of rats to 24 h light, a procedure which produces a supersensitive response to beta-adrenergic stimulation, results in a 50% increase in protein kinase activity (with or without added cAMP) as compared to the activity in pineals obtained after 12 h darkness, when the glands are subsensitive. Kinetic analysis revealed a 50-100% increase in the Vmax for ATP, histone, and cAMP. This increase in protein kinase was not prevented by prior treatment of rats with cycloheximide. The diminished kinase activity in subsensitive glands did not appear to be due to an increase in the heat-stable protein kinase inhibitor. Protein kinase activity also increased (in the presence or absence of added cAMP) after noradrenergic input to the gland was reduced by denervation or depletion of neurotransmitter. Thus, pineal protein kinase may participate in the effects of beta-adrenergic agonists (e.g. the induction of serotonin N-acetyltransferase) and in the regulation of the sensitivity of the gland to beta-adrenergic stimulation.", "contents": "Regulation of protein kinase in rat pineal: increased Vmax in supersensitive glands. Protein kinase activity was examined in supernatants from super-sensitive and subsensitive rat pineal glands both in the presence and absence of added cAMP. After a 20 min exposure to 1-isoproterenol, in vivo or in organ culture, supersensitive pineals displayed a greater decrease in protein kinase activity (in the absence of added cAMP) than did subsensitive glands. Furthermore, exposure of rats to 24 h light, a procedure which produces a supersensitive response to beta-adrenergic stimulation, results in a 50% increase in protein kinase activity (with or without added cAMP) as compared to the activity in pineals obtained after 12 h darkness, when the glands are subsensitive. Kinetic analysis revealed a 50-100% increase in the Vmax for ATP, histone, and cAMP. This increase in protein kinase was not prevented by prior treatment of rats with cycloheximide. The diminished kinase activity in subsensitive glands did not appear to be due to an increase in the heat-stable protein kinase inhibitor. Protein kinase activity also increased (in the presence or absence of added cAMP) after noradrenergic input to the gland was reduced by denervation or depletion of neurotransmitter. Thus, pineal protein kinase may participate in the effects of beta-adrenergic agonists (e.g. the induction of serotonin N-acetyltransferase) and in the regulation of the sensitivity of the gland to beta-adrenergic stimulation."}
{"id": "PMID:190283", "title": "Maturational delay and temporal growth retardation in asthmatic boys.", "content": "Growth in height, bone age, and sexual maturation have been studied in asthmatic boys 2 to 20 yr of age. The mean pattern of growth in height has been analyzed mixed-longitudinally in 531 patients (1,754 measures) and seemed to be determined by a delay in physiologic maturation. The asthmatic boys' growth in height showed no retardation during infancy, a small but consistent retardation during childhood, a more pronounced delay at adolescence, and a catch-up growth toward adulthood. The mean adolescent growth spurt is delayed by about 1.3 yr. Bone age has been analyzed mixed-longitudinally in a subsample of 370 patients (660 observations) and showed a slight retardation at all ages between 6 and 13 yr. Development of pubic hair of 91 subjects analyzed cross-sectionally was definitely retarded when compared to adequate reference data. Evidence was given that factors secondary to the asthmatic syndrome are involved in the retardation of growth and development.", "contents": "Maturational delay and temporal growth retardation in asthmatic boys. Growth in height, bone age, and sexual maturation have been studied in asthmatic boys 2 to 20 yr of age. The mean pattern of growth in height has been analyzed mixed-longitudinally in 531 patients (1,754 measures) and seemed to be determined by a delay in physiologic maturation. The asthmatic boys' growth in height showed no retardation during infancy, a small but consistent retardation during childhood, a more pronounced delay at adolescence, and a catch-up growth toward adulthood. The mean adolescent growth spurt is delayed by about 1.3 yr. Bone age has been analyzed mixed-longitudinally in a subsample of 370 patients (660 observations) and showed a slight retardation at all ages between 6 and 13 yr. Development of pubic hair of 91 subjects analyzed cross-sectionally was definitely retarded when compared to adequate reference data. Evidence was given that factors secondary to the asthmatic syndrome are involved in the retardation of growth and development."}
{"id": "PMID:190288", "title": "Enzymes of glucose metabolism in palmar fascia and Dupuytren's contracture.", "content": "Several enzymes participating in glucose metabolism and some of the acid hydrolases were assayed in palmar fascia and Dupuytren's contracture with fluorometric microanalytical methods. The enzyme activities of glucose metabolism were lower in normal palmar fascia than in dermis. The fascia of Dupuytren's contracture exhibited a general increase in the enzyme activities of glucose catabolism. Little alteration was found in alanine aminotransferase and UDP-glucose dehydrogenase activity in the lesion. Lysosomal hydrolytic enzyme activities were increased five to ten times in Dupuytren's tissue. The dermis overlying Dupuytren's contracture exhibited an increase in the enzyme activities of glucose catabolism, but to a lesser degree than did the fascia of the lesion. The epidermis of involved palmar skin displayed normal enzyme activities.", "contents": "Enzymes of glucose metabolism in palmar fascia and Dupuytren's contracture. Several enzymes participating in glucose metabolism and some of the acid hydrolases were assayed in palmar fascia and Dupuytren's contracture with fluorometric microanalytical methods. The enzyme activities of glucose metabolism were lower in normal palmar fascia than in dermis. The fascia of Dupuytren's contracture exhibited a general increase in the enzyme activities of glucose catabolism. Little alteration was found in alanine aminotransferase and UDP-glucose dehydrogenase activity in the lesion. Lysosomal hydrolytic enzyme activities were increased five to ten times in Dupuytren's tissue. The dermis overlying Dupuytren's contracture exhibited an increase in the enzyme activities of glucose catabolism, but to a lesser degree than did the fascia of the lesion. The epidermis of involved palmar skin displayed normal enzyme activities."}
{"id": "PMID:190311", "title": "Oxidation of tissue polysaccharides by periodic acid in dimethyl sulfoxide and its anhydrous and aqueous mixtures.", "content": "Periodic acid (1% w/v) solvated by anhydrous dimethyl sulfoxide (DMSO) readily induced a strong Schiff reaction in a variety of structures containing polysaccharides, but not glycogen. With the increasing amounts of water added to DMSO, glycogen was also oxidized, while the selective localization of other polysaccharides remained unimpaired. Periodate, solvated in the anhydrous acetic acid-DMSO mixture, rapidly induced concomitant oxidation of nucin and glycogen-containing structures. Sodium bisulfite addition derivatives of carbonyls, induced by periodate oxidation in DMSO, were stained meta- and orthochromatically with toluidine blue at controlled pH. Certain metachromatic tissue components were strongly birefringent in polarized light in contrast to the identical structures oxidized by aqueous periodate. Marked differences in staining reactions elicited in identical structures by periodate in DMSO as compared with aqueous periodate suggest that DMSO-periodate method considerably enhances the range of histochemical oxidations by periodate.", "contents": "Oxidation of tissue polysaccharides by periodic acid in dimethyl sulfoxide and its anhydrous and aqueous mixtures. Periodic acid (1% w/v) solvated by anhydrous dimethyl sulfoxide (DMSO) readily induced a strong Schiff reaction in a variety of structures containing polysaccharides, but not glycogen. With the increasing amounts of water added to DMSO, glycogen was also oxidized, while the selective localization of other polysaccharides remained unimpaired. Periodate, solvated in the anhydrous acetic acid-DMSO mixture, rapidly induced concomitant oxidation of nucin and glycogen-containing structures. Sodium bisulfite addition derivatives of carbonyls, induced by periodate oxidation in DMSO, were stained meta- and orthochromatically with toluidine blue at controlled pH. Certain metachromatic tissue components were strongly birefringent in polarized light in contrast to the identical structures oxidized by aqueous periodate. Marked differences in staining reactions elicited in identical structures by periodate in DMSO as compared with aqueous periodate suggest that DMSO-periodate method considerably enhances the range of histochemical oxidations by periodate."}
{"id": "PMID:190312", "title": "Stress, cardiac activity and sleep.", "content": "An overview is presented of the relationship between cardiovascular activity and sleep, emphasizing the interrelations between stage of sleep and cardiovascular dysfunction. Possible implications of the data are discussed, especially in relation to stress-related factors and possible treatment regimens.", "contents": "Stress, cardiac activity and sleep. An overview is presented of the relationship between cardiovascular activity and sleep, emphasizing the interrelations between stage of sleep and cardiovascular dysfunction. Possible implications of the data are discussed, especially in relation to stress-related factors and possible treatment regimens."}
{"id": "PMID:190313", "title": "Direct and cooperative mechanisms of lymphocyte triggering in liquid and solid cultures.", "content": "The role of cell interactions in lymphocyte stimulation was analyzed by studying the kinetics of lymphocyte proliferation at different cell concentrations, and also by a lymphocyte microculture technique in solid medium. An absolute requirement for cell interactions was found in lymphocyte responses to concanavalin A, pokeweed mitogen, sodium periodate, purified protein derivative from Mycobacterium tuberculosis, and zinc chloride. No requirement for cell interactions was found in lymphocyte responses to calcium ionophore A23187. The existence of lymphocyte subpopulations with different requirements for cell interactions was observed in lymphocyte responses to phytohemagglutinin P, phytohemagglutinin HA 17, tetradecanoyl-phorbolacetate, antiserum to MOLT-4 lymphoblasts, antiserum to B411-4 lymphoblasts, antiserum to human embryo lung fibroblasts, and antiserum to HeLa cells infected with Herpes simplex virus. Lymphocyte responses to phytohemagglutinin P were potentiated by incorporation into the solid cultures of red blood cells of their membrane preparations suggesting that membrane-membrane interactions, either directly, or through soluble mediators are likely to be the basis of cell cooperation in this system. In solid cultures, phytohemagglutinin P, phytohemagglutinin P plus red blood cells, phytohemagglutinin HA 17, tetradecanoyl-phorbol-acetate and antiserum to MOLT-4 lymphoblasts were found to stimulate mainly thymus-dependent lymphocytes, whereas antiserum to Hela cells infected with Herpes simplex virus stimulated mainly non-thymus-dependent lymphocytes. Antiserum to B411-4 lymphoblasts stimulated both thymus-dependent and non-thymus dependent lymphocytes.", "contents": "Direct and cooperative mechanisms of lymphocyte triggering in liquid and solid cultures. The role of cell interactions in lymphocyte stimulation was analyzed by studying the kinetics of lymphocyte proliferation at different cell concentrations, and also by a lymphocyte microculture technique in solid medium. An absolute requirement for cell interactions was found in lymphocyte responses to concanavalin A, pokeweed mitogen, sodium periodate, purified protein derivative from Mycobacterium tuberculosis, and zinc chloride. No requirement for cell interactions was found in lymphocyte responses to calcium ionophore A23187. The existence of lymphocyte subpopulations with different requirements for cell interactions was observed in lymphocyte responses to phytohemagglutinin P, phytohemagglutinin HA 17, tetradecanoyl-phorbolacetate, antiserum to MOLT-4 lymphoblasts, antiserum to B411-4 lymphoblasts, antiserum to human embryo lung fibroblasts, and antiserum to HeLa cells infected with Herpes simplex virus. Lymphocyte responses to phytohemagglutinin P were potentiated by incorporation into the solid cultures of red blood cells of their membrane preparations suggesting that membrane-membrane interactions, either directly, or through soluble mediators are likely to be the basis of cell cooperation in this system. In solid cultures, phytohemagglutinin P, phytohemagglutinin P plus red blood cells, phytohemagglutinin HA 17, tetradecanoyl-phorbol-acetate and antiserum to MOLT-4 lymphoblasts were found to stimulate mainly thymus-dependent lymphocytes, whereas antiserum to Hela cells infected with Herpes simplex virus stimulated mainly non-thymus-dependent lymphocytes. Antiserum to B411-4 lymphoblasts stimulated both thymus-dependent and non-thymus dependent lymphocytes."}
{"id": "PMID:190314", "title": "Antigen induced alterations in splenic prostaglandin and cyclic nucleotide levels in NZB mice.", "content": "Studies were undertaken in order to determine if NZB mice injected with sheep erythrocyte antigens would respond by showing elevated splenic prostaglandin and cyclic nucleotide levels similar to that observed in normal mice. The results show that young NZB mice can respond to sheep erythrocytes by yielding increased levels of splenic PGF2alpha and cAMP. However, because of increased basal levels of PGF2alpha and cAMP, the net increase observed is lower than that observed with normal mice. In old NZB mice exhibiting signs of disease (splenomegaly) and in which defects in immune competence are known to occur, the injection of SRBC results in in no increase in splenic PGF2alpha levels and a decrease in cAMP levels. These animals also have greatly elevated basal levels of PGF2alpha, cAMP, and cGMP. It is concluded that the cellular immune defect in NZB mice is reflected by their faulty metabolic responses to sRBC. Also, the altered basal levels of PG and cyclic nucleotides may be related to the altered cellular immune competence. The latter conclusion is supported by the reduced capacity of spleen cells from young NZB mice to respond to PGE by increasing cAMP levels and by the lack of an effect of inhibitors of PG synthesis on the immune response to sRBC in both young and old NZB mouse spleen cell cultures.", "contents": "Antigen induced alterations in splenic prostaglandin and cyclic nucleotide levels in NZB mice. Studies were undertaken in order to determine if NZB mice injected with sheep erythrocyte antigens would respond by showing elevated splenic prostaglandin and cyclic nucleotide levels similar to that observed in normal mice. The results show that young NZB mice can respond to sheep erythrocytes by yielding increased levels of splenic PGF2alpha and cAMP. However, because of increased basal levels of PGF2alpha and cAMP, the net increase observed is lower than that observed with normal mice. In old NZB mice exhibiting signs of disease (splenomegaly) and in which defects in immune competence are known to occur, the injection of SRBC results in in no increase in splenic PGF2alpha levels and a decrease in cAMP levels. These animals also have greatly elevated basal levels of PGF2alpha, cAMP, and cGMP. It is concluded that the cellular immune defect in NZB mice is reflected by their faulty metabolic responses to sRBC. Also, the altered basal levels of PG and cyclic nucleotides may be related to the altered cellular immune competence. The latter conclusion is supported by the reduced capacity of spleen cells from young NZB mice to respond to PGE by increasing cAMP levels and by the lack of an effect of inhibitors of PG synthesis on the immune response to sRBC in both young and old NZB mouse spleen cell cultures."}
{"id": "PMID:190315", "title": "Isolation and characterization of immunoregulatory factors from normal human serum. I. Preliminary biochemical and biological characterization of immunosuppressive factors.", "content": "Normal human serum was shown to inhibit the mitogenic effects of bacterial lipopolysaccharide and Con A on mouse spleen lymphocytes and reduce the in vitro antibody response to SRBC by these cells. Furthermore, it was demonstrated that immune suppression occurred without loss of lymphocyte viability. Fractionation of normal human serum resulted in isolation of several immunoenhancing and immunoinhibitory fractions. Electrophoretic analysis of the immunoinhibitory fractions revealed a complex array of serum proteins. The most prominent proteins on polyacrylamide electrophoresis stained for both proteins and carbohydrate. The heterogeneity of immunoinhibitory fractions were further substantiated by their differential susceptibility to trypsin, periodate, and 2-mercaptoethanol treatment. Heterogeneity of the fractions was also shown to be related to difference in their biologic activity as expressed in their effects on mitogenicity and immunogenicity of LPS in mouse splenic cultures. This study lends evidence to the consideration that normal human serum contains several immunoregulatory factors with differing biochemical characteristics and cellular sites of action.", "contents": "Isolation and characterization of immunoregulatory factors from normal human serum. I. Preliminary biochemical and biological characterization of immunosuppressive factors. Normal human serum was shown to inhibit the mitogenic effects of bacterial lipopolysaccharide and Con A on mouse spleen lymphocytes and reduce the in vitro antibody response to SRBC by these cells. Furthermore, it was demonstrated that immune suppression occurred without loss of lymphocyte viability. Fractionation of normal human serum resulted in isolation of several immunoenhancing and immunoinhibitory fractions. Electrophoretic analysis of the immunoinhibitory fractions revealed a complex array of serum proteins. The most prominent proteins on polyacrylamide electrophoresis stained for both proteins and carbohydrate. The heterogeneity of immunoinhibitory fractions were further substantiated by their differential susceptibility to trypsin, periodate, and 2-mercaptoethanol treatment. Heterogeneity of the fractions was also shown to be related to difference in their biologic activity as expressed in their effects on mitogenicity and immunogenicity of LPS in mouse splenic cultures. This study lends evidence to the consideration that normal human serum contains several immunoregulatory factors with differing biochemical characteristics and cellular sites of action."}
{"id": "PMID:190316", "title": "The mononuclear cell in human blood which mediates antibody-dependent cellular cytotoxicity to virus-infected target cells. I. Identification of the population of effector cells.", "content": "Mononuclear cells (MC) from human blood were fractionated by a variety of physical and immunologic techniques, and the cellular subpopulations generated were assessed for their capacity to lyse herpes simplex virus (HSV)-infected target cells in the presence of IgG antibody to HSV. Latex phagocytosis and surface marker studies were performed in parallel in order to identify the major effector cells by their phagocytic properties and their possession of surface immunoglobulin and receptors for either sheep erythrocytes, C3, or the Fc fragment of IgG. Cytotoxic effector cell activity was unaffected or slightly enhanced after the removal of plastic-adherent or carbonyl iron-adherent MC, indicating that the major effector cell is not a classical monocyte. Similar results were obtained after removal of more than 90% of the T cells by depletion of rosette-forming cells. Likewise, effector cell activity was generally unchanged when more than 95% of the B cells were removed by filtering MC on nylon wool columns. Effector cell function was also found to be normal in three patients with B cell-deficient X-linked agammaglobulinemia. These observations strongly suggest that the effector cells are not T cells or B cells. A 4- to 5-fold enrichment in effector cells, however, was consistently found in a subpopulation, consisting of 5% of the unfractionated MC, that was dramatically enriched both for nonphagocytic cells with only Fc receptor (K cells) and for nonphagocytic cells with no detectable surface markers (null cells). Since, as is demonstrated in the accompanying report, effector surface Fc receptors play a critical role in the mediation of antibody-dependent cellular cytotoxicity directed at HSV-infected target cells, the major mononuclear effector cell in human blood is a K cell.", "contents": "The mononuclear cell in human blood which mediates antibody-dependent cellular cytotoxicity to virus-infected target cells. I. Identification of the population of effector cells. Mononuclear cells (MC) from human blood were fractionated by a variety of physical and immunologic techniques, and the cellular subpopulations generated were assessed for their capacity to lyse herpes simplex virus (HSV)-infected target cells in the presence of IgG antibody to HSV. Latex phagocytosis and surface marker studies were performed in parallel in order to identify the major effector cells by their phagocytic properties and their possession of surface immunoglobulin and receptors for either sheep erythrocytes, C3, or the Fc fragment of IgG. Cytotoxic effector cell activity was unaffected or slightly enhanced after the removal of plastic-adherent or carbonyl iron-adherent MC, indicating that the major effector cell is not a classical monocyte. Similar results were obtained after removal of more than 90% of the T cells by depletion of rosette-forming cells. Likewise, effector cell activity was generally unchanged when more than 95% of the B cells were removed by filtering MC on nylon wool columns. Effector cell function was also found to be normal in three patients with B cell-deficient X-linked agammaglobulinemia. These observations strongly suggest that the effector cells are not T cells or B cells. A 4- to 5-fold enrichment in effector cells, however, was consistently found in a subpopulation, consisting of 5% of the unfractionated MC, that was dramatically enriched both for nonphagocytic cells with only Fc receptor (K cells) and for nonphagocytic cells with no detectable surface markers (null cells). Since, as is demonstrated in the accompanying report, effector surface Fc receptors play a critical role in the mediation of antibody-dependent cellular cytotoxicity directed at HSV-infected target cells, the major mononuclear effector cell in human blood is a K cell."}
{"id": "PMID:190317", "title": "The direct antiviral cytotoxicity by bovine lymphocytes is not restricted by genetic incompatibility of lymphocytes and target cells.", "content": "Experiments were designed to determine if in the ox a requirement for genetic compatibility between antiviral cytotoxic cells and target cells was needed for cytotoxicity to occur. Unrelated bovine animals were immunized with vaccinia or IBR virus (a herpesvirus), and PBL were collected at various times for measurement of their cytotoxicity against autologous or heterologous uninfected or virus-infected fibroblasts. In all instances, cytotoxicity was expressed against heterologous as well as autologous targets and in most cases there was no evidence of enhanced killing of autologous cells. The cytotoxicity was shown to be direct, presumably T cell mediated, and was not attributable to ADCC. The likelihood of the animals under investigation sharing histocompatibility antigens was considered extremely remote but was not formally excluded.", "contents": "The direct antiviral cytotoxicity by bovine lymphocytes is not restricted by genetic incompatibility of lymphocytes and target cells. Experiments were designed to determine if in the ox a requirement for genetic compatibility between antiviral cytotoxic cells and target cells was needed for cytotoxicity to occur. Unrelated bovine animals were immunized with vaccinia or IBR virus (a herpesvirus), and PBL were collected at various times for measurement of their cytotoxicity against autologous or heterologous uninfected or virus-infected fibroblasts. In all instances, cytotoxicity was expressed against heterologous as well as autologous targets and in most cases there was no evidence of enhanced killing of autologous cells. The cytotoxicity was shown to be direct, presumably T cell mediated, and was not attributable to ADCC. The likelihood of the animals under investigation sharing histocompatibility antigens was considered extremely remote but was not formally excluded."}
{"id": "PMID:190318", "title": "In vivo suppression of the primary immune response by a species of low density serum lipoprotein.", "content": "An apparent subspecies of normal human serum low density lipoprotein (LDL-In) has been identified with suppressive activity for early or facilitating events of human lymphocyte mitogen and allogenic cells stimulation in vitro. This report describes the effects of in vivo administration of LDL-In on the mouse anti-SRBC immune response. Human LDL-In is not species specific and was capable of suppressing the in vivo mouse anti-sheep erythrocyte (SRBC) hemagglutination response by 88% after the administration of 500 to 600 mug LDL-In IV, whereas human serum high density lipoproteins and fibrinogen had no effect. Maximal suppression occurred only when LDL-In was injected 24 to 48 hr before antigen administration. Simultaneous or subsequent injection of LDL-In had no effect. The activity of LDL-In was influenced by antigen dose and maximal at low antigen doses. The number of splenic plaque-forming cells was also reduced indicating a suppression of the clonal expansion of primary B cells to antibody-secreting cells rather than only suppression of antibody synthesis by differentiated B cells and their progeny. These observations suggest the hypothesis that endogenous LDL-In could play an important immunoregulatory role in the maintenance of immune homeostasis and the \"natural\" suppression of non-productive lymphocyte proliferation.", "contents": "In vivo suppression of the primary immune response by a species of low density serum lipoprotein. An apparent subspecies of normal human serum low density lipoprotein (LDL-In) has been identified with suppressive activity for early or facilitating events of human lymphocyte mitogen and allogenic cells stimulation in vitro. This report describes the effects of in vivo administration of LDL-In on the mouse anti-SRBC immune response. Human LDL-In is not species specific and was capable of suppressing the in vivo mouse anti-sheep erythrocyte (SRBC) hemagglutination response by 88% after the administration of 500 to 600 mug LDL-In IV, whereas human serum high density lipoproteins and fibrinogen had no effect. Maximal suppression occurred only when LDL-In was injected 24 to 48 hr before antigen administration. Simultaneous or subsequent injection of LDL-In had no effect. The activity of LDL-In was influenced by antigen dose and maximal at low antigen doses. The number of splenic plaque-forming cells was also reduced indicating a suppression of the clonal expansion of primary B cells to antibody-secreting cells rather than only suppression of antibody synthesis by differentiated B cells and their progeny. These observations suggest the hypothesis that endogenous LDL-In could play an important immunoregulatory role in the maintenance of immune homeostasis and the \"natural\" suppression of non-productive lymphocyte proliferation."}
{"id": "PMID:190319", "title": "Genetic factors infuencing mouse type-C RNA virus induction by naturally occurring B cell mitogens.", "content": "The present studies demonstrate that xenotropic type C virus is efficiently released in response to lipopolysaccharide by spleen cells of a wide variety of inbred mouse strains. Lipopolysaccharide-mediated virus release primarily involves B lymphocytes and is in part genetically determined. Virus release can also be efficiently stimulated by other naturally occurring B cell mitogens, including Nocardia water soluble mitogen, and PPD. The evidence indicates that these agents act synergistically with halogeneated pyrimidines, but not with each other, to cause virus release. These results indicate that B cell mitogens act to release virus by a mechanism that differs from that of halogenated pyrimidines.", "contents": "Genetic factors infuencing mouse type-C RNA virus induction by naturally occurring B cell mitogens. The present studies demonstrate that xenotropic type C virus is efficiently released in response to lipopolysaccharide by spleen cells of a wide variety of inbred mouse strains. Lipopolysaccharide-mediated virus release primarily involves B lymphocytes and is in part genetically determined. Virus release can also be efficiently stimulated by other naturally occurring B cell mitogens, including Nocardia water soluble mitogen, and PPD. The evidence indicates that these agents act synergistically with halogeneated pyrimidines, but not with each other, to cause virus release. These results indicate that B cell mitogens act to release virus by a mechanism that differs from that of halogenated pyrimidines."}
{"id": "PMID:190320", "title": "Solid-phase radioimmunoassay of herpes simplex virus IgG and IgM antibodies.", "content": "A solid-phase radioimmunoassay for detection of herpes simplex virus-specific IgG and IgM antibodies in human serum specimens is presented. Virus antigen is adsorbed on polystyrene balls and antibodies which attach to the antigen are detected by 125I-labeled antihuman-gamma or antihuman-mu immunoglobulins. A total of 76 specimens have been tested. The appearance of virus-specific IgG and IgM antibodies in primary herpetic infections was readily demonstrated. When serum samples from patients with past exposure to herpes simplex virus were tested, endpoint titers of virus-specific IgG antibodies were found to be 8 to 2048 times higher than titers determined by a complement fixation test. Apparent cross reactivity with varicella-zoster virus was observed in the present radioimmunoassay.", "contents": "Solid-phase radioimmunoassay of herpes simplex virus IgG and IgM antibodies. A solid-phase radioimmunoassay for detection of herpes simplex virus-specific IgG and IgM antibodies in human serum specimens is presented. Virus antigen is adsorbed on polystyrene balls and antibodies which attach to the antigen are detected by 125I-labeled antihuman-gamma or antihuman-mu immunoglobulins. A total of 76 specimens have been tested. The appearance of virus-specific IgG and IgM antibodies in primary herpetic infections was readily demonstrated. When serum samples from patients with past exposure to herpes simplex virus were tested, endpoint titers of virus-specific IgG antibodies were found to be 8 to 2048 times higher than titers determined by a complement fixation test. Apparent cross reactivity with varicella-zoster virus was observed in the present radioimmunoassay."}
{"id": "PMID:190321", "title": "Correlation of apparent molecular weight and antigenicity of viral proteins: an SDS-page separation followed by acrylamide-agarose electrophoresis and immunoprecipitation.", "content": "A simple method is described which combines a sodium dodecyl sulfate polyacrylamide gel electrophoresis (SOS-PAGE) in the first demension with a second electrophoresis, at right angles to the first, into an agarose matrix. The proteins, separated by SDS-PAGE, are exposed to appropriate antisera after the second stage electrophoresis and immunoprecipitates form in the agarose corresponding to the relative electrophoretic mobilities of proteins in the first stage SDS-PAGE separation. The method thus provides a simple, reproducible means for correlating antigenicity with apparent molecular weight of proteins. The technique is qualtitative, but requires smaller quantities of antisera than more conventional immunoelectrophoretic methods such as rocket electrophoresis.", "contents": "Correlation of apparent molecular weight and antigenicity of viral proteins: an SDS-page separation followed by acrylamide-agarose electrophoresis and immunoprecipitation. A simple method is described which combines a sodium dodecyl sulfate polyacrylamide gel electrophoresis (SOS-PAGE) in the first demension with a second electrophoresis, at right angles to the first, into an agarose matrix. The proteins, separated by SDS-PAGE, are exposed to appropriate antisera after the second stage electrophoresis and immunoprecipitates form in the agarose corresponding to the relative electrophoretic mobilities of proteins in the first stage SDS-PAGE separation. The method thus provides a simple, reproducible means for correlating antigenicity with apparent molecular weight of proteins. The technique is qualtitative, but requires smaller quantities of antisera than more conventional immunoelectrophoretic methods such as rocket electrophoresis."}
{"id": "PMID:190326", "title": "The role of human skin collagenase in epidermolysis bullosa.", "content": "Human skin collagenase was quantitated by radioimmunoassay in 40 patients with various forms of epidermolysis bullosa to compare levels of the enzyme in blistered and clinically unaffected skin. Immunoreactive human skin collagenase was significantly elevated in the blistered skin of patients with both recessive and dominant forms of dystrophic epidermolysis bullosa (DEB). In addition, patients with generalized recessive DEB manifested a 4-fold increase in collagenase protein in normal-appearing skin, and patients with localized recessive DEB or epidermolysis bullosa letalis showed a 3-t to 3.5-fold elevation in the enzyme. However, patients with dominantly inherited DEB failed to displays a statistically significant increase in immunoreactive collagenase in nonblistered skin. Although it cannot be definitely stated whether the elevated collagenase content in the blistered skin represents a primary or secondary event, such as part of a wound healing response, the demonstration of markedly increased levels of collagenase in normal-appearing skin could, in part, provide an explanation at the molecular level for the formation of blisters in this disease.", "contents": "The role of human skin collagenase in epidermolysis bullosa. Human skin collagenase was quantitated by radioimmunoassay in 40 patients with various forms of epidermolysis bullosa to compare levels of the enzyme in blistered and clinically unaffected skin. Immunoreactive human skin collagenase was significantly elevated in the blistered skin of patients with both recessive and dominant forms of dystrophic epidermolysis bullosa (DEB). In addition, patients with generalized recessive DEB manifested a 4-fold increase in collagenase protein in normal-appearing skin, and patients with localized recessive DEB or epidermolysis bullosa letalis showed a 3-t to 3.5-fold elevation in the enzyme. However, patients with dominantly inherited DEB failed to displays a statistically significant increase in immunoreactive collagenase in nonblistered skin. Although it cannot be definitely stated whether the elevated collagenase content in the blistered skin represents a primary or secondary event, such as part of a wound healing response, the demonstration of markedly increased levels of collagenase in normal-appearing skin could, in part, provide an explanation at the molecular level for the formation of blisters in this disease."}
{"id": "PMID:190327", "title": "Accumulation of cyclic adenosine 3',5'-monophosphate in adult and newborn mouse skin: responses to ischemia and isoproterenol.", "content": "Levels of cyclic adenosine 3',5'-monophosphate in adult mouse skin pieces were rapidly increased on incubation at 37 degrees C, or on exposure to isoproterenol. Accumulation of the cyclic nucleotide under both conditions was greatly decreased in newborn mouse skin, or in adult skin treated with the tumor promotor 12-0-tetradecanoyl-phorbol-13-acetate.", "contents": "Accumulation of cyclic adenosine 3',5'-monophosphate in adult and newborn mouse skin: responses to ischemia and isoproterenol. Levels of cyclic adenosine 3',5'-monophosphate in adult mouse skin pieces were rapidly increased on incubation at 37 degrees C, or on exposure to isoproterenol. Accumulation of the cyclic nucleotide under both conditions was greatly decreased in newborn mouse skin, or in adult skin treated with the tumor promotor 12-0-tetradecanoyl-phorbol-13-acetate."}
{"id": "PMID:190328", "title": "Effects of topical prostaglandin E analogue on normal hairless mouse epidermal DNA synthesis.", "content": "The in vivo topical effects of a synthetic analogue of prostaglandin E2 (15(S)-15-methyl PGE2 methyl ester [PGE2 analogue]), have been studied on the epidermis of hairless mice. One microgram of the PGE2 analogue increased DNA synthesis significantly by 5 hr, a maximum increase of 390% was reached by 12 hr, and DNA synthesis returned to control levels by 24 hr. Twenty micrograms of the PGE2 analogue reduced epidermal DNA synthesis for 12 hr after application, DNA synthesis was increased at 24 hr, returning to control levels by 48 hr. One hundred micrograms of topical PGE2 had no significant effect on epidermal DNA synthesis over 48 hr, but 1 mug of intradermal PGE2 increased DNA synthesis by 160% at 24 hr. These results suggest that topical 15(S)-15-methyl PGE2 methyl ester is biologically active compared with PGE2.", "contents": "Effects of topical prostaglandin E analogue on normal hairless mouse epidermal DNA synthesis. The in vivo topical effects of a synthetic analogue of prostaglandin E2 (15(S)-15-methyl PGE2 methyl ester [PGE2 analogue]), have been studied on the epidermis of hairless mice. One microgram of the PGE2 analogue increased DNA synthesis significantly by 5 hr, a maximum increase of 390% was reached by 12 hr, and DNA synthesis returned to control levels by 24 hr. Twenty micrograms of the PGE2 analogue reduced epidermal DNA synthesis for 12 hr after application, DNA synthesis was increased at 24 hr, returning to control levels by 48 hr. One hundred micrograms of topical PGE2 had no significant effect on epidermal DNA synthesis over 48 hr, but 1 mug of intradermal PGE2 increased DNA synthesis by 160% at 24 hr. These results suggest that topical 15(S)-15-methyl PGE2 methyl ester is biologically active compared with PGE2."}
{"id": "PMID:190329", "title": "Variation in enterotoxigenicity of Escherichia coli.", "content": "The possibility that the variable severity of diarrheal disease due to enterotoxigenic Escherichia coli might be explained by quantitative differences in the activity of heat-labile enterotoxin was examined. The amount of toxin secreted by 13 enteropathogenic strains of E. coli was quantitated by measurements of the toxin-dependent increase in adenosine 3':5'-cyclic phosphate (cyclic AMP) in Chinese hamster ovary cells. The activity ranged from 150 pmol of cyclic AMP/ml per mg of protein to 4,040 pmol/ml per mg. With three representative strains there was good correlation (r = -0.999; P less than 0.05) between the amounts of cyclic AMP accumulated intracellularly (4,040, 2,071, and 470 pmol of cyclic AMP/ml per mg of protein) and the ability of the filtrate to distend the rabbit ileal loop, as measured by the amounts of toxin required to produce half-maximal distension (50% effective dose, which had values of 11.5, 27.5, and 38.5 mg, respectively). The observed strain-to-strain variation in toxin activity may explain the variation in severity of diarrheal disease caused by enterotoxigenic E. coli.", "contents": "Variation in enterotoxigenicity of Escherichia coli. The possibility that the variable severity of diarrheal disease due to enterotoxigenic Escherichia coli might be explained by quantitative differences in the activity of heat-labile enterotoxin was examined. The amount of toxin secreted by 13 enteropathogenic strains of E. coli was quantitated by measurements of the toxin-dependent increase in adenosine 3':5'-cyclic phosphate (cyclic AMP) in Chinese hamster ovary cells. The activity ranged from 150 pmol of cyclic AMP/ml per mg of protein to 4,040 pmol/ml per mg. With three representative strains there was good correlation (r = -0.999; P less than 0.05) between the amounts of cyclic AMP accumulated intracellularly (4,040, 2,071, and 470 pmol of cyclic AMP/ml per mg of protein) and the ability of the filtrate to distend the rabbit ileal loop, as measured by the amounts of toxin required to produce half-maximal distension (50% effective dose, which had values of 11.5, 27.5, and 38.5 mg, respectively). The observed strain-to-strain variation in toxin activity may explain the variation in severity of diarrheal disease caused by enterotoxigenic E. coli."}
{"id": "PMID:190330", "title": "Complement-fixing antigen of human cytomegaloviruses.", "content": "The titer of complement-fixing (CF) antigen of human cytomegalovirus (CMV) strain C87 was not reduced by 10 cycles of freezing and thawing or by storage at 4 C for two months, although the virus was labile at 37 C and 100 C. The rapid increase in titers of CF antigen and plaque-forming units was seen from days 3 through 6 after infection; however, CF antigen was detected 24 hr after infection. The molecular weight of CF antigen was estimated by gel filtration to be greater than 1.5 X 10(7) daltons. Electrophoresis of CF antigens from five strains of human CMV (AD169, C87, Espilant [Esp.], Davis, and Towne) in a gradient polyacrylamide gel slab in the presence of sodium dodecyl sulfate revealed two specific polypeptides with molecular weights of 140,000 and 66,000 daltons, respectively. The smaller polypeptide was glycosylated. Preparations of CF antigen from murine CMV and herpes simplex virus type 1 contained polypeptides of 140,000 and 145,000 daltons, respectively. However, the polypeptide with a molecular weight of 66,000 daltons was seen only in preparations of human CMV.", "contents": "Complement-fixing antigen of human cytomegaloviruses. The titer of complement-fixing (CF) antigen of human cytomegalovirus (CMV) strain C87 was not reduced by 10 cycles of freezing and thawing or by storage at 4 C for two months, although the virus was labile at 37 C and 100 C. The rapid increase in titers of CF antigen and plaque-forming units was seen from days 3 through 6 after infection; however, CF antigen was detected 24 hr after infection. The molecular weight of CF antigen was estimated by gel filtration to be greater than 1.5 X 10(7) daltons. Electrophoresis of CF antigens from five strains of human CMV (AD169, C87, Espilant [Esp.], Davis, and Towne) in a gradient polyacrylamide gel slab in the presence of sodium dodecyl sulfate revealed two specific polypeptides with molecular weights of 140,000 and 66,000 daltons, respectively. The smaller polypeptide was glycosylated. Preparations of CF antigen from murine CMV and herpes simplex virus type 1 contained polypeptides of 140,000 and 145,000 daltons, respectively. However, the polypeptide with a molecular weight of 66,000 daltons was seen only in preparations of human CMV."}
{"id": "PMID:190331", "title": "Cellular localization of hepatitis B virus antigens in patients with hepatocellular carcinoma coexisting with liver cirrhosis.", "content": "Specimens of liver tissue obtained by biopsy from five patients and at necropsy from seven patients with postnecrotic liver cirrhosis and hepatocellular carcinoma were examined for the presence of hepatitis B surface antigen (HBs Ag) and hepatitis B core antigen (HBc Ag) by direct immunofluorescence. In all cases, samples of serum were tested for HBs Ag and antibody to HBs Ag (anti-HBs) by immunoelectroosmophoresis and for antibody to HBc Ag (anti-HBc) by indirect immunofluorescence. Of these 12 representative cases of the main histological types of hepatocellular carcinoma, six were found to be seropositive for anti-HBc, and three of them were negative for HBs Ag. HBs Ag was detected in the cytoplasm of hepatocytes in the cirrhotic nodules in one seronegative patient and in three of the seropositive cases. In the latter cases, HBs Ag was identified in the cytoplasm of cells in well-differentiated hepatocellular carcinoma. HBc Ag was not found in any of the specimens examined.", "contents": "Cellular localization of hepatitis B virus antigens in patients with hepatocellular carcinoma coexisting with liver cirrhosis. Specimens of liver tissue obtained by biopsy from five patients and at necropsy from seven patients with postnecrotic liver cirrhosis and hepatocellular carcinoma were examined for the presence of hepatitis B surface antigen (HBs Ag) and hepatitis B core antigen (HBc Ag) by direct immunofluorescence. In all cases, samples of serum were tested for HBs Ag and antibody to HBs Ag (anti-HBs) by immunoelectroosmophoresis and for antibody to HBc Ag (anti-HBc) by indirect immunofluorescence. Of these 12 representative cases of the main histological types of hepatocellular carcinoma, six were found to be seropositive for anti-HBc, and three of them were negative for HBs Ag. HBs Ag was detected in the cytoplasm of hepatocytes in the cirrhotic nodules in one seronegative patient and in three of the seropositive cases. In the latter cases, HBs Ag was identified in the cytoplasm of cells in well-differentiated hepatocellular carcinoma. HBc Ag was not found in any of the specimens examined."}
{"id": "PMID:190333", "title": "Synaptic transmission in the sixth ganglion of the cockroach: action of 4-aminopyridine.", "content": "1. Study was made of the action of 4-aminopyridine (5 X 10(-5) M) on synaptic transmission in the last abdominal ganglion of Periplaneta americana. The 'oil-gap' technique was used to record postsynaptic events in a single giant axon. 2. 4-AP quickly increased the 'background' of postsynaptic activity, which consisted of 'spontaneous' unitary EPSPs and IPSPs. Postsynaptic spikes were also propagated. 3. Both evoked EPSPs (stimulation of cercal nerve XI) and evoked IPSPs (stimulation of cercal nerve X) were greatly increased in amplitude although their duration (half-time) was unaltered. 4. 4-AP triggered presynaptic action potentials in the cercal nerves (recorded with external electrodes). These 'antidromic' potentials appeared singly or sometimes repetitively, especially after electrical stimulation of the cercal nerves. They were often in monosynaptic correlation with unitary EPSPs. 5. Neither the resting potential nor the postsynaptic membrane resistance was modified. 6. There were no changes in the equilibrium potentials of the ions involved in postsynaptic events. 7. The results may be essentially explained by an increase in transmitter release after 4-AP treatment, which may be partly the result of a rise in presynaptic terminal excitability, and partly the result of a lengthening of the presynaptic action potentials.", "contents": "Synaptic transmission in the sixth ganglion of the cockroach: action of 4-aminopyridine. 1. Study was made of the action of 4-aminopyridine (5 X 10(-5) M) on synaptic transmission in the last abdominal ganglion of Periplaneta americana. The 'oil-gap' technique was used to record postsynaptic events in a single giant axon. 2. 4-AP quickly increased the 'background' of postsynaptic activity, which consisted of 'spontaneous' unitary EPSPs and IPSPs. Postsynaptic spikes were also propagated. 3. Both evoked EPSPs (stimulation of cercal nerve XI) and evoked IPSPs (stimulation of cercal nerve X) were greatly increased in amplitude although their duration (half-time) was unaltered. 4. 4-AP triggered presynaptic action potentials in the cercal nerves (recorded with external electrodes). These 'antidromic' potentials appeared singly or sometimes repetitively, especially after electrical stimulation of the cercal nerves. They were often in monosynaptic correlation with unitary EPSPs. 5. Neither the resting potential nor the postsynaptic membrane resistance was modified. 6. There were no changes in the equilibrium potentials of the ions involved in postsynaptic events. 7. The results may be essentially explained by an increase in transmitter release after 4-AP treatment, which may be partly the result of a rise in presynaptic terminal excitability, and partly the result of a lengthening of the presynaptic action potentials."}
{"id": "PMID:190334", "title": "The hormonal control of diuresis in the cabbage white butterfly Pieris brassicae.", "content": "The diuresis which follows the pupal-adult ecdysis of Pieris brassicae is hormonally controlled. Use of the isolated Malpighian tubules as a bioassay shows the presence of substantial diuretic activity in homogenates of the brain and corpus cardiacum-corpus allatum complex. The hormone is probably produced in the brain and released from a storage site in the corpora cardiaca. The tubules of the butterfly are maximally responsive to the diuretic hormone at the time of eclosion.", "contents": "The hormonal control of diuresis in the cabbage white butterfly Pieris brassicae. The diuresis which follows the pupal-adult ecdysis of Pieris brassicae is hormonally controlled. Use of the isolated Malpighian tubules as a bioassay shows the presence of substantial diuretic activity in homogenates of the brain and corpus cardiacum-corpus allatum complex. The hormone is probably produced in the brain and released from a storage site in the corpora cardiaca. The tubules of the butterfly are maximally responsive to the diuretic hormone at the time of eclosion."}
{"id": "PMID:190336", "title": "The design and use of a health status index for family physicians.", "content": "This paper describes a Health Status Index (HSI) which is part of a patient encounter form in a family practice center. The Index, which is used to profile a patient's health status longitudinally, combines physical and psychosocial measures of health. Based on its use in the center and through the presentation of data on patient health status, the authors illustrate how the Index can facilitate the evaluation of care and the management of practice. More specifically, they suggest that such data assist physicians in: (1) evaluating the effect of different modes of treatment on the duration and severity of ill-defined symptoms and complaints; (2) identifying high-risk patients for special attention; (3) indicating treatment modalities which produce more desirable outcomes; (4) determining the efficiency of different modes of treatment and of continued care; and (5) addressing chronological, as well as interpersonal and interprofessional, questions of providing continuous care for the chronically ill.", "contents": "The design and use of a health status index for family physicians. This paper describes a Health Status Index (HSI) which is part of a patient encounter form in a family practice center. The Index, which is used to profile a patient's health status longitudinally, combines physical and psychosocial measures of health. Based on its use in the center and through the presentation of data on patient health status, the authors illustrate how the Index can facilitate the evaluation of care and the management of practice. More specifically, they suggest that such data assist physicians in: (1) evaluating the effect of different modes of treatment on the duration and severity of ill-defined symptoms and complaints; (2) identifying high-risk patients for special attention; (3) indicating treatment modalities which produce more desirable outcomes; (4) determining the efficiency of different modes of treatment and of continued care; and (5) addressing chronological, as well as interpersonal and interprofessional, questions of providing continuous care for the chronically ill."}
{"id": "PMID:190338", "title": "Calcium-activated conductance in skate electroreceptors: current clamp experiments.", "content": "When current clamped, skate electroreceptor epithelium produces large action potentials in response to stimuli that depolarize the lumenal faces of the receptor cells. With increasing stimulus strength these action potentials become prolonged. When the peak voltage exceeds about 140 mV the repolarizing phase is blocked until the end of the stimulus. Perfusion experiments show that the rising phase of the action potential results from an increase in calcium permeability in the lumenal membranes. Perfusion of the lumen with cobalt or with a zero calcium solution containing EGTA blocks the action potential. Perfusion of the lumen with a solution containing 10 mM Ca and 20 mM EGTA initially slows the repolarizing process at all voltages and lowers the potential at which it is blocked. With prolonged perfusion, repolarization is blocked at all voltages. When excitability is abolished by perfusion with cobalt, or with a zero calcium solution containing EGTA, no delayed rectification occurs. We suggest that repolarization during the action potential depends on an influx of calcium into the cytoplasm, and that the rate of repolarization depends on the magnitude of the inward calcium current. Increasingly large stimuli reduce the rate of repolarization by reducing the driving force for calcium, and then block repolarization by causing the lumenal membrane potential to exceed ECa. Changes in extracellular calcium affect repolarization in a manner consistent with the resulting change in ECa.", "contents": "Calcium-activated conductance in skate electroreceptors: current clamp experiments. When current clamped, skate electroreceptor epithelium produces large action potentials in response to stimuli that depolarize the lumenal faces of the receptor cells. With increasing stimulus strength these action potentials become prolonged. When the peak voltage exceeds about 140 mV the repolarizing phase is blocked until the end of the stimulus. Perfusion experiments show that the rising phase of the action potential results from an increase in calcium permeability in the lumenal membranes. Perfusion of the lumen with cobalt or with a zero calcium solution containing EGTA blocks the action potential. Perfusion of the lumen with a solution containing 10 mM Ca and 20 mM EGTA initially slows the repolarizing process at all voltages and lowers the potential at which it is blocked. With prolonged perfusion, repolarization is blocked at all voltages. When excitability is abolished by perfusion with cobalt, or with a zero calcium solution containing EGTA, no delayed rectification occurs. We suggest that repolarization during the action potential depends on an influx of calcium into the cytoplasm, and that the rate of repolarization depends on the magnitude of the inward calcium current. Increasingly large stimuli reduce the rate of repolarization by reducing the driving force for calcium, and then block repolarization by causing the lumenal membrane potential to exceed ECa. Changes in extracellular calcium affect repolarization in a manner consistent with the resulting change in ECa."}
{"id": "PMID:190339", "title": "Analysis of herpes simplex virus DNA synthesized in infected nuclei by chromatography on benzoylated naphthoylated DEAE cellulose columns.", "content": "The nature of the DNA molecules synthesized in nuclei of herpes simplex virus (HSV)-infected cells in vivo and in vitro was studied by chromatography on BND-cellulose columns after shearing to DNA fragments of 10 to 20 X 10(6) daltons. The incorporation of labelled precursors occurs in the DNA fragments containing single-stranded regions, presumably the replication forks. Prolongation of DNA synthesis leads to the accumulation of labelled DNA fragments that lack single-stranded sequences. Analysis of the isolated DNA fragments by density centrifugation in CSCl gradients revealed that most of the labelled DNA molecules are of virus specificity and the minority are cellular DNA fragments. Double-stranded virus DNA fragments and virus DNA fragments containing single-stranded sequences band in CSCl gradients at a density of 1-718 g/ml, the density of virion DNA. This suggests that the replicating HSV DNA molecules have the same density as the virion DNA and contain relatively little single-stranded DNA. The synthesis of HSV DNA molecules under in vitro conditions in isolated nuclei occurs by incorporation of the precursors into DNA fragments with single-stranded regions. The synthesis of cellular DNA in nuclei from hydroxyurea and cytosine arabinoside treated cells also occurs by elongation of nascent DNA chains.", "contents": "Analysis of herpes simplex virus DNA synthesized in infected nuclei by chromatography on benzoylated naphthoylated DEAE cellulose columns. The nature of the DNA molecules synthesized in nuclei of herpes simplex virus (HSV)-infected cells in vivo and in vitro was studied by chromatography on BND-cellulose columns after shearing to DNA fragments of 10 to 20 X 10(6) daltons. The incorporation of labelled precursors occurs in the DNA fragments containing single-stranded regions, presumably the replication forks. Prolongation of DNA synthesis leads to the accumulation of labelled DNA fragments that lack single-stranded sequences. Analysis of the isolated DNA fragments by density centrifugation in CSCl gradients revealed that most of the labelled DNA molecules are of virus specificity and the minority are cellular DNA fragments. Double-stranded virus DNA fragments and virus DNA fragments containing single-stranded sequences band in CSCl gradients at a density of 1-718 g/ml, the density of virion DNA. This suggests that the replicating HSV DNA molecules have the same density as the virion DNA and contain relatively little single-stranded DNA. The synthesis of HSV DNA molecules under in vitro conditions in isolated nuclei occurs by incorporation of the precursors into DNA fragments with single-stranded regions. The synthesis of cellular DNA in nuclei from hydroxyurea and cytosine arabinoside treated cells also occurs by elongation of nascent DNA chains."}
{"id": "PMID:190340", "title": "Mechanism of interferon action: further evidence for transcription as the primary site of action in simian virus 40 infection.", "content": "Interferon inhibits the replication of simian virus 40 (SV40) in monkey cells and reduces markedly the formation of both early virus protein (i.e. SV40 T antigen) and early SV40 RNA. This suggests that in SV40 infection interferon acts primarily by inhibiting transcription. To test this conclusion further, we examined alternative mechanisms which might explain these results and made the following observations. (1) The quantity of input SV40 DNA in the nucleus 24 h post infection (p.i.) was the same in interferon-treated and control cells. Thus interferon does not appear to diminish the quantity of SV40 DNA template available for transcription. (2) Chemical inhibitors of protein synthesis did not mimic the selective inhibition of early SV40 RNA formation induced by interferon, indicating that the transcription of early SV40 RNA is not dependent upon the prior synthesis of any virus-induced protein. Thus a block in translation cannot readily explain the reduced formation of early SV40 RNA in interferon-treated cells. (3) Fractionation of SV40 infected cells after a one-hour labelling period showed that interferon produced a comparable reduction in the quantity of early SV40 RNA in the nucleus and the cytoplasm. Thus the observed inhibition of early SV40 RNA is not due solely (if at all) to enhanced cytoplasmic degradation. These results indicate that the primary effect of interferon in SV40 infected monkey cells is either to inhibit the transcription of early virus RNA or to enhance its turnover in the nucleus.", "contents": "Mechanism of interferon action: further evidence for transcription as the primary site of action in simian virus 40 infection. Interferon inhibits the replication of simian virus 40 (SV40) in monkey cells and reduces markedly the formation of both early virus protein (i.e. SV40 T antigen) and early SV40 RNA. This suggests that in SV40 infection interferon acts primarily by inhibiting transcription. To test this conclusion further, we examined alternative mechanisms which might explain these results and made the following observations. (1) The quantity of input SV40 DNA in the nucleus 24 h post infection (p.i.) was the same in interferon-treated and control cells. Thus interferon does not appear to diminish the quantity of SV40 DNA template available for transcription. (2) Chemical inhibitors of protein synthesis did not mimic the selective inhibition of early SV40 RNA formation induced by interferon, indicating that the transcription of early SV40 RNA is not dependent upon the prior synthesis of any virus-induced protein. Thus a block in translation cannot readily explain the reduced formation of early SV40 RNA in interferon-treated cells. (3) Fractionation of SV40 infected cells after a one-hour labelling period showed that interferon produced a comparable reduction in the quantity of early SV40 RNA in the nucleus and the cytoplasm. Thus the observed inhibition of early SV40 RNA is not due solely (if at all) to enhanced cytoplasmic degradation. These results indicate that the primary effect of interferon in SV40 infected monkey cells is either to inhibit the transcription of early virus RNA or to enhance its turnover in the nucleus."}
{"id": "PMID:190341", "title": "Isolation of subviral components from transmissible gastroenteritis virus.", "content": "Exposure of purified transmissible gastroenteritis virus, a porcine coronavirus, to non-ionic detergents resulted in the removal of the surface projections and greater than 98% of the virus lipid. Virus RNA was associated with a subviral particle which had a sedimentation coefficient of 650S, compared with 495S for the intact virion, and which banded in Cs2SO4 gradients at 1-295 g/ml. Negatively stained preparations of subviral particles were shown by electron microscopy to contain spherical particles of 60 to 70 nm diam., similar in appearance to those derived from oncornaviruses. Polyacrylamide gel electrophoresis of the polypeptides from isolated subviral particles showed that these structures contained three of the four major virus structural proteins, the arginine-rich polypeptide VP2 and the two membrane glycopolypeptides VP2 and 4. The detergent-liberated surface projections, composed of a single species of sulphated glycopolypeptide, VPI, were isolated by rate-zonal centrifugation through sucrose gradients followed by precipitation with ammonium sulphate in the presence of bovine serum albumin.", "contents": "Isolation of subviral components from transmissible gastroenteritis virus. Exposure of purified transmissible gastroenteritis virus, a porcine coronavirus, to non-ionic detergents resulted in the removal of the surface projections and greater than 98% of the virus lipid. Virus RNA was associated with a subviral particle which had a sedimentation coefficient of 650S, compared with 495S for the intact virion, and which banded in Cs2SO4 gradients at 1-295 g/ml. Negatively stained preparations of subviral particles were shown by electron microscopy to contain spherical particles of 60 to 70 nm diam., similar in appearance to those derived from oncornaviruses. Polyacrylamide gel electrophoresis of the polypeptides from isolated subviral particles showed that these structures contained three of the four major virus structural proteins, the arginine-rich polypeptide VP2 and the two membrane glycopolypeptides VP2 and 4. The detergent-liberated surface projections, composed of a single species of sulphated glycopolypeptide, VPI, were isolated by rate-zonal centrifugation through sucrose gradients followed by precipitation with ammonium sulphate in the presence of bovine serum albumin."}
{"id": "PMID:190342", "title": "Evidence for early nuclear antigens in cytomegalovirus-infected cells.", "content": "Human cytomegalovirus (CMV) induces nuclear antigens resembling the Epstein-Barr nuclear antigen (EBNA) as early as 3 h after infection. These early antigens can be detected only with the anti-complement immunofluorescence staining (ACIF) technique. Synthesis of these new antigens is not influenced by cytosine arabinoside (ara-C).", "contents": "Evidence for early nuclear antigens in cytomegalovirus-infected cells. Human cytomegalovirus (CMV) induces nuclear antigens resembling the Epstein-Barr nuclear antigen (EBNA) as early as 3 h after infection. These early antigens can be detected only with the anti-complement immunofluorescence staining (ACIF) technique. Synthesis of these new antigens is not influenced by cytosine arabinoside (ara-C)."}
{"id": "PMID:190343", "title": "In vitro synthesis of herpes simplex virus DNA in nuclei isolated from infected BSC 1 cells.", "content": "The synthesis of herpes simplex virus DNA in isolated nuclei under in vitro conditions was found to be dependent on the addition of ATP and an ATP generating system to the reaction mixture. In vitro DNA synthesis was stimulated and prolonged when p-hydroxymercuribenzoate was added to the isolated nuclei. Under these improved conditions virus DNA molecules which were initiated in vivo were completed in vitro, but most of the DNA molecules synthesized in vitro sedimented in sucrose gradients more slowly than herpes virion DNA. Denaturation of the in vitro labelled DNA molecules produced short single-stranded labelled DNA chains. Thus, under our improved in vitro conditions there was prolonged synthesis of DNA at a high rate, with the formation of both complete and incomplete virus DNA molecules.", "contents": "In vitro synthesis of herpes simplex virus DNA in nuclei isolated from infected BSC 1 cells. The synthesis of herpes simplex virus DNA in isolated nuclei under in vitro conditions was found to be dependent on the addition of ATP and an ATP generating system to the reaction mixture. In vitro DNA synthesis was stimulated and prolonged when p-hydroxymercuribenzoate was added to the isolated nuclei. Under these improved conditions virus DNA molecules which were initiated in vivo were completed in vitro, but most of the DNA molecules synthesized in vitro sedimented in sucrose gradients more slowly than herpes virion DNA. Denaturation of the in vitro labelled DNA molecules produced short single-stranded labelled DNA chains. Thus, under our improved in vitro conditions there was prolonged synthesis of DNA at a high rate, with the formation of both complete and incomplete virus DNA molecules."}
{"id": "PMID:190344", "title": "Effect of concanavalin A on vesicular stomatitis virus maturation.", "content": "Addition of concanavalin A to BHK cell monolayers infected with vesicular stomatitis virus prevented the formation of mature virus particles. In these cells the virus glycoprotein (G) was inserted into the plasma membrane and the protein that is in close association with the ribonucleic acid, protein N, was found in the cytoplasm. At times when cells infected in the absence of the lectin were liberating virus into the supernatant medium, the M or matrix protein was found in association with the plasma membrane of the lectin-treated cells. The removal of the lectin from the cells with alpha-methyl-D-glucoside 3 h after infection was followed by the immediate release of mature virus particles. The rate of virus release from these cells was the same as that from cells infected in the absence of the lectin. Addition of cycloheximide, and inhibitor of protein synthesis, immediately after alpha-methyl-D-glucoside treatment of the cells did not alter the rate of virus production, suggesting that the proteins required for virus synthesis were available in the lectin-treated cells and that virus assembly took place without further protein synthesis on removal of the lectin.", "contents": "Effect of concanavalin A on vesicular stomatitis virus maturation. Addition of concanavalin A to BHK cell monolayers infected with vesicular stomatitis virus prevented the formation of mature virus particles. In these cells the virus glycoprotein (G) was inserted into the plasma membrane and the protein that is in close association with the ribonucleic acid, protein N, was found in the cytoplasm. At times when cells infected in the absence of the lectin were liberating virus into the supernatant medium, the M or matrix protein was found in association with the plasma membrane of the lectin-treated cells. The removal of the lectin from the cells with alpha-methyl-D-glucoside 3 h after infection was followed by the immediate release of mature virus particles. The rate of virus release from these cells was the same as that from cells infected in the absence of the lectin. Addition of cycloheximide, and inhibitor of protein synthesis, immediately after alpha-methyl-D-glucoside treatment of the cells did not alter the rate of virus production, suggesting that the proteins required for virus synthesis were available in the lectin-treated cells and that virus assembly took place without further protein synthesis on removal of the lectin."}
{"id": "PMID:190345", "title": "Characterization of the Drosophila C virus.", "content": "Some properties of Drosophila C virus (DCV), a non-occluded isometric virus, have been studied. The virus particles were 30 nm in diam., their sedimentation coefficient was 153S and their buoyant density was 1-34 g/ml in caesium chloride in the pH range 7 to 9. These particles contained about 31% ribonucleic acid (RNA) and 69% protein. The reaction of formaldehyde with DCV particles suggested that the RNA in situ is single-stranded. The infectivity of DCV was stable at pH 3. The virus capsid contained three major polypeptides with mol. wt. of 31000, 30000 and 28000, and two minor components of mol. wt. 37000 and 8500. Virus preparations also contained a small number of infective particles 24 nm in diam. banding at a density of 1-44 g/ml. Preliminary results indicated that these heavy particles probably correspond to the dense particles recently reported in several vertebrate picornaviruses. RNA extracted from DCV was single-stranded and infectious. Its mol. wt. was calculated to be approx 3 X 10(6). It is proposed that this virus be included in the enterovirus group. The crytogram of the virus is R/1:3.0/31:S/S:I/O.", "contents": "Characterization of the Drosophila C virus. Some properties of Drosophila C virus (DCV), a non-occluded isometric virus, have been studied. The virus particles were 30 nm in diam., their sedimentation coefficient was 153S and their buoyant density was 1-34 g/ml in caesium chloride in the pH range 7 to 9. These particles contained about 31% ribonucleic acid (RNA) and 69% protein. The reaction of formaldehyde with DCV particles suggested that the RNA in situ is single-stranded. The infectivity of DCV was stable at pH 3. The virus capsid contained three major polypeptides with mol. wt. of 31000, 30000 and 28000, and two minor components of mol. wt. 37000 and 8500. Virus preparations also contained a small number of infective particles 24 nm in diam. banding at a density of 1-44 g/ml. Preliminary results indicated that these heavy particles probably correspond to the dense particles recently reported in several vertebrate picornaviruses. RNA extracted from DCV was single-stranded and infectious. Its mol. wt. was calculated to be approx 3 X 10(6). It is proposed that this virus be included in the enterovirus group. The crytogram of the virus is R/1:3.0/31:S/S:I/O."}
{"id": "PMID:190346", "title": "Mechanism of polykaryocyte induction by vesicular stomatitis virus in rat XC cells.", "content": "Vesicular stomatitis virus (VSV) induces polykaryocytes in rat embryonic fibroblasts transformed by the Prague strain of Rous sarcoma virus (XC cells). The cell fusion requires the uncoating of the virus in the cell, the synthesis of normally structured G and M proteins and their incorporation into the cell membrane. The synthesis of fully infectious virus is unnecessary. In addition to these antigens, a special yet undefined constitution of the host membrane is also important. With thermosensitive mutants non-defective for G and M antigens, cell fusion is much more extensive at the non-permissive temperature (39-6 degrees C) than at the permissive one (31 degrees C). The importance of these two antigens is also shown using rifampicin-sensitive mutants. We postulate that these two antigens induce in the cell membrane an imbalance in the distribution of phospholipids which then diffuse through membrane junctions to surrounding cells, provoking thereafter the cell fusion.", "contents": "Mechanism of polykaryocyte induction by vesicular stomatitis virus in rat XC cells. Vesicular stomatitis virus (VSV) induces polykaryocytes in rat embryonic fibroblasts transformed by the Prague strain of Rous sarcoma virus (XC cells). The cell fusion requires the uncoating of the virus in the cell, the synthesis of normally structured G and M proteins and their incorporation into the cell membrane. The synthesis of fully infectious virus is unnecessary. In addition to these antigens, a special yet undefined constitution of the host membrane is also important. With thermosensitive mutants non-defective for G and M antigens, cell fusion is much more extensive at the non-permissive temperature (39-6 degrees C) than at the permissive one (31 degrees C). The importance of these two antigens is also shown using rifampicin-sensitive mutants. We postulate that these two antigens induce in the cell membrane an imbalance in the distribution of phospholipids which then diffuse through membrane junctions to surrounding cells, provoking thereafter the cell fusion."}
{"id": "PMID:190347", "title": "The size and location of the poly(A) tract in EMC virus RNA.", "content": "Encephalomyocarditis (EMC) virus RNA, selected by its affinity for oligo(dT)-cellulose, contains poly(A) of size : (i) about 14 nucleotide residues long, based on the percentage of radioactivity in the RNA resistant to digestion by a mixture of pancreatic and T1 RNases; (ii) about 15 residues long, as measured by the ratio of the amount of terminal adenosine to internal adenylic acid in isolated poly(A); and (III) in the range 12 to 45 residues, the majority of tracts being about 16 to 18 residues long, based upon electrophoretic mobility on polyacrylamide gels using poly(A) molecules of known size as mol. wt. markers. The poly(A) appears to be located at the 3'-terminus of the virus genome since the tract, liberated by digestion with a mixture of pancreatic and T1 RNases, was shown by compositional analysis to contain a non-phosphorylated 3'-terminus and only adenine residues. The size heterogeneity in the poly(A) tracts revealed by gel electrophoresis is also consistent with a terminal location. Comparison of our data for EMC virus with published data for other picornaviruses suggests that the sizes of poly(A) tracts in polio- and Mengovirus RNA have been overestimated; poly(A) tracts in cardioviruses appear to be smaller than those in poliovirus; the minimum size of poly(A) required for full infectivity of picornavirus RNA has also been overestimated; a tract of at least 13 adenine residues long is required for full infectivity of EMC virus RNA.", "contents": "The size and location of the poly(A) tract in EMC virus RNA. Encephalomyocarditis (EMC) virus RNA, selected by its affinity for oligo(dT)-cellulose, contains poly(A) of size : (i) about 14 nucleotide residues long, based on the percentage of radioactivity in the RNA resistant to digestion by a mixture of pancreatic and T1 RNases; (ii) about 15 residues long, as measured by the ratio of the amount of terminal adenosine to internal adenylic acid in isolated poly(A); and (III) in the range 12 to 45 residues, the majority of tracts being about 16 to 18 residues long, based upon electrophoretic mobility on polyacrylamide gels using poly(A) molecules of known size as mol. wt. markers. The poly(A) appears to be located at the 3'-terminus of the virus genome since the tract, liberated by digestion with a mixture of pancreatic and T1 RNases, was shown by compositional analysis to contain a non-phosphorylated 3'-terminus and only adenine residues. The size heterogeneity in the poly(A) tracts revealed by gel electrophoresis is also consistent with a terminal location. Comparison of our data for EMC virus with published data for other picornaviruses suggests that the sizes of poly(A) tracts in polio- and Mengovirus RNA have been overestimated; poly(A) tracts in cardioviruses appear to be smaller than those in poliovirus; the minimum size of poly(A) required for full infectivity of picornavirus RNA has also been overestimated; a tract of at least 13 adenine residues long is required for full infectivity of EMC virus RNA."}
{"id": "PMID:190348", "title": "Interferon inhibits mouse leukaemia virus release: an electron microscope study.", "content": "Scanning electron microscopy of AKR cells chronically infected with AKR mouse leukaemia virus revealed that the number of budding virions was greatly increased in interferon-treated cells. These results, together with previous biochemical findings, suggest that in this system, interferon inhibits a late stage of virus assembly or release.", "contents": "Interferon inhibits mouse leukaemia virus release: an electron microscope study. Scanning electron microscopy of AKR cells chronically infected with AKR mouse leukaemia virus revealed that the number of budding virions was greatly increased in interferon-treated cells. These results, together with previous biochemical findings, suggest that in this system, interferon inhibits a late stage of virus assembly or release."}
{"id": "PMID:190349", "title": "Suitability of Epstein-Barr virus DNA obtained from superinfected Raji cells for complementary RNA hybridization studies.", "content": "A method was established to obtain a high yield of Epstein-Barr virus (EBV) DNA for nucleic acid hybridization studies on latent virus DNA in transformed cells. Superinfection of Raji cells with EBV concentrated from HRI cell cultures produced a 600-fold higher yield of EBV DNA than direct isolation of EBV from HRI cell cultures. The virus DNA thus prepared from Raji cells superinfected with EBV was radioisotopically and spectrophotometrically pure and served as a satisfactory template for the preparation of cRNA specific to EBV DNA.", "contents": "Suitability of Epstein-Barr virus DNA obtained from superinfected Raji cells for complementary RNA hybridization studies. A method was established to obtain a high yield of Epstein-Barr virus (EBV) DNA for nucleic acid hybridization studies on latent virus DNA in transformed cells. Superinfection of Raji cells with EBV concentrated from HRI cell cultures produced a 600-fold higher yield of EBV DNA than direct isolation of EBV from HRI cell cultures. The virus DNA thus prepared from Raji cells superinfected with EBV was radioisotopically and spectrophotometrically pure and served as a satisfactory template for the preparation of cRNA specific to EBV DNA."}
{"id": "PMID:190351", "title": "Neurotrophic control of cyclic nucleotide levels during muscle differentiation in cell culture.", "content": "The effects of chick brain-spinal cord extract on morphological development and cyclic nucleotide levels of cultured chick embryo skeletal muscle cells were determined. It had previously been shown that the extract stimulated morphological differentiation, protein synthesis, and choliniesterase activity of muscle cells. Myoblasts fused earlier and an increase in number as well as diameter of myotubes were seen in the extract treated cultures. Cyclic nucleotides levels were higher (almost twice the controls for both adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate) and preceded their occurrence in the control cultures. It was suggested that factor(s) in the extract interact with membrane receptor(s) to alter nucleotide levels which, in turn, allow the effects to be expressed.", "contents": "Neurotrophic control of cyclic nucleotide levels during muscle differentiation in cell culture. The effects of chick brain-spinal cord extract on morphological development and cyclic nucleotide levels of cultured chick embryo skeletal muscle cells were determined. It had previously been shown that the extract stimulated morphological differentiation, protein synthesis, and choliniesterase activity of muscle cells. Myoblasts fused earlier and an increase in number as well as diameter of myotubes were seen in the extract treated cultures. Cyclic nucleotides levels were higher (almost twice the controls for both adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate) and preceded their occurrence in the control cultures. It was suggested that factor(s) in the extract interact with membrane receptor(s) to alter nucleotide levels which, in turn, allow the effects to be expressed."}
{"id": "PMID:190352", "title": "Myelin subfractions isolated from mouse brain. Studies of normal mice during development, quaking mutants, and three brain regions.", "content": "Myelin isolated from three areas of mouse brain, from whole brain at several ages in normal mice, and from whole brain of adult quaking mutant mice was separated into seven bands and a pellet on discontinuous density gradients using 0.32, 0.45, 0.55, 0.60, 0.70, 0.75 and 0.85 M sucrose. The distribution of myelin in the subfractions was independent of homogenization and shocking conditions employed to isolate the myelin preparations, but was related to the type of myelin applied to the gradient. Compared to myelin isolated from older animals, myelin isolated from 18-24 day old mice displayed a distribution pattern with greater proportions of material banding at lesser sucrose densities. Similarly, myelin obtained from hindbrain contained proportionately more material layering at lesser sucrose densities compared to myelin isolated from cerebral cortex. Myelin subfraction patterns observed for 8-12 day old control mice and quaking mutants were unlike each other or any other myelin preparation examined. In the 18-90 days old animals, the markers studied were not uniformly distributed among the myelin subfractions. The pellet and the layer banding at the 0.75/0.85 M sucrose interface contained the highest specific concentrations of sialic acid, nucleic acid, and total adenosine triphosphatase activity. In contrast, the specific activity of 2',3'-cyclicnucleotide-3'-phosphohydrolase was lowest in the pellet as well as the three bands obtained above 0.60 M sucrose and was highest in the fraction banding at the 0.65/0.70 M sucrose interface. The results obtained were not consistent with an artifactual origin of the myelin subfractions, but instead suggested that the subfraction have physiological significance. One explanation for the different banding patterns observed between young and mature myelin may be the different amount of myelin in various brain regions during development.", "contents": "Myelin subfractions isolated from mouse brain. Studies of normal mice during development, quaking mutants, and three brain regions. Myelin isolated from three areas of mouse brain, from whole brain at several ages in normal mice, and from whole brain of adult quaking mutant mice was separated into seven bands and a pellet on discontinuous density gradients using 0.32, 0.45, 0.55, 0.60, 0.70, 0.75 and 0.85 M sucrose. The distribution of myelin in the subfractions was independent of homogenization and shocking conditions employed to isolate the myelin preparations, but was related to the type of myelin applied to the gradient. Compared to myelin isolated from older animals, myelin isolated from 18-24 day old mice displayed a distribution pattern with greater proportions of material banding at lesser sucrose densities. Similarly, myelin obtained from hindbrain contained proportionately more material layering at lesser sucrose densities compared to myelin isolated from cerebral cortex. Myelin subfraction patterns observed for 8-12 day old control mice and quaking mutants were unlike each other or any other myelin preparation examined. In the 18-90 days old animals, the markers studied were not uniformly distributed among the myelin subfractions. The pellet and the layer banding at the 0.75/0.85 M sucrose interface contained the highest specific concentrations of sialic acid, nucleic acid, and total adenosine triphosphatase activity. In contrast, the specific activity of 2',3'-cyclicnucleotide-3'-phosphohydrolase was lowest in the pellet as well as the three bands obtained above 0.60 M sucrose and was highest in the fraction banding at the 0.65/0.70 M sucrose interface. The results obtained were not consistent with an artifactual origin of the myelin subfractions, but instead suggested that the subfraction have physiological significance. One explanation for the different banding patterns observed between young and mature myelin may be the different amount of myelin in various brain regions during development."}
{"id": "PMID:190356", "title": "Giant axonal neuropathy. Report of a case with normal hair.", "content": "A further case of giant axonal neuropathy is described. The diagnosis was made by sural nerve biopsy in a boy presenting signs of a progressive spinocerebellar syndrome with polyneuropathy. Ultrastructurally a severe abnormality of this peripheral nerve, with loss of thick myelinated nerve fibers and the presence of giant axonal swellings was evident. The axonal swellings appeared to be caused by an accumulation of filaments which were also present in Schwann cells, as well as in endothelial and perineurial cells, justifying the term of \"generalized microfibrillar hyperplasia\". It is most remarkable that the patient's hair was not unusual, in contrast to the previously reported cases who had \"kinky hair\".", "contents": "Giant axonal neuropathy. Report of a case with normal hair. A further case of giant axonal neuropathy is described. The diagnosis was made by sural nerve biopsy in a boy presenting signs of a progressive spinocerebellar syndrome with polyneuropathy. Ultrastructurally a severe abnormality of this peripheral nerve, with loss of thick myelinated nerve fibers and the presence of giant axonal swellings was evident. The axonal swellings appeared to be caused by an accumulation of filaments which were also present in Schwann cells, as well as in endothelial and perineurial cells, justifying the term of \"generalized microfibrillar hyperplasia\". It is most remarkable that the patient's hair was not unusual, in contrast to the previously reported cases who had \"kinky hair\"."}
{"id": "PMID:190360", "title": "Quaking mouse: an ultrastructural study of the peripheral nerves.", "content": "Ultrastructural study of the peripheral nervous system of quaking mice has revealed several unusual features in the pattern of myelination in addition to hypomyelination. These are 1) the presence of 'atypical' Schmidt-Lanterman incisures, 2) irregularities of the nodal and internodal termination of Schwann cell cytoplasm and 3) the presence of non-myelinated segments without associated Schwann cell processes, but covered by basal lamina. In view of the observation of similar features during the development of the P.N.S. and also during P.N.S. remyelination, we suggest that these features are the results of modified myelination due to a defect in the control mechanisms necessary for normal myelination.", "contents": "Quaking mouse: an ultrastructural study of the peripheral nerves. Ultrastructural study of the peripheral nervous system of quaking mice has revealed several unusual features in the pattern of myelination in addition to hypomyelination. These are 1) the presence of 'atypical' Schmidt-Lanterman incisures, 2) irregularities of the nodal and internodal termination of Schwann cell cytoplasm and 3) the presence of non-myelinated segments without associated Schwann cell processes, but covered by basal lamina. In view of the observation of similar features during the development of the P.N.S. and also during P.N.S. remyelination, we suggest that these features are the results of modified myelination due to a defect in the control mechanisms necessary for normal myelination."}
{"id": "PMID:190361", "title": "Chemotherapeutic trials on human malignant astrocytomas in organ culture.", "content": "A technique of organ culture based on a three-dimensional porous matrix was employed for chemotherapeutic trials on human malignant astrocytomas. The method allows neoplasms to retain the morphological identity and the histological characteristics they possess in vivo. Success in culture was greatest with high-grade astrocytomas, the majority of which showed definite infiltration of the matrix. Low-grade tumors, if viable, did not display active penetration. Drug trials on eight malignant astrocytomas included BCNU, methyl CCNU, VP 16-213, and Solu-Medrol. Cyanide and luciferase were used as experimental metabolic toxins. Evidence of cytotoxicity was assesed qualitatively by histological changes on microscopic preparations of treated and control cultures. Microfluorometric determinations of reduced nicotinamide adenine dinucleotide (NADH) were applied to these trials in an effort to detect a quantitative biochemical index of drug effects. A variable rise in although correlation with microscopic changes was inconsistent. Because of its potential merits, organ culture may be a valuable tool for further work on pharmacological management of malignant gliomas.", "contents": "Chemotherapeutic trials on human malignant astrocytomas in organ culture. A technique of organ culture based on a three-dimensional porous matrix was employed for chemotherapeutic trials on human malignant astrocytomas. The method allows neoplasms to retain the morphological identity and the histological characteristics they possess in vivo. Success in culture was greatest with high-grade astrocytomas, the majority of which showed definite infiltration of the matrix. Low-grade tumors, if viable, did not display active penetration. Drug trials on eight malignant astrocytomas included BCNU, methyl CCNU, VP 16-213, and Solu-Medrol. Cyanide and luciferase were used as experimental metabolic toxins. Evidence of cytotoxicity was assesed qualitatively by histological changes on microscopic preparations of treated and control cultures. Microfluorometric determinations of reduced nicotinamide adenine dinucleotide (NADH) were applied to these trials in an effort to detect a quantitative biochemical index of drug effects. A variable rise in although correlation with microscopic changes was inconsistent. Because of its potential merits, organ culture may be a valuable tool for further work on pharmacological management of malignant gliomas."}
{"id": "PMID:190357", "title": "Ultrastructural studies of the dying-back process. III. The evolution of experimental peripheral giant axonal degeneration.", "content": "The spatio-temporal evolution of peripheral giant axonal degeneration has been studied in rats during the development of concurrent peripheral (PNS) and central (CNS) nervous system dying-back disease after chronic intoxication with the neurotoxic hexacarbons n-hexane (CH3CH2CH2CH2CH2CH3), methyl n-butyl ketone (MBK) (CH3COCH2CH2CH2CH3), or 2,5-hexanedione (CH3COCH2CH2CHOCH3), a neurotoxic metabolite of MBK. Each compound caused animals insidiously to develop identical, symmetrical peripheral neuropathies characterized by eversion and drop of hindfeet, inability to extend hindlimbs and upper extremity weakness. Teased fiber studies demonstrated that giant axonal swellings first developed on the proximal sides of multiple paranodes sited in distal, non-terminal regions of large myelinated fibers. Later, swellings developed at internodal sites. Smaller myelinated and unmyelinated fibers also underwent multifocal, giant axonal swelling. In affected myelinated fibers, swollen nodal and paranodal axons were frequently associated with retracted paranodal myelin sheaths. Adjacent distal internodes were attenuated and corrugated. Demyelinated paranodes apparently underwent local shrinkage and remyelination before complete distal fiber breakdown commenced. The proximal limits of chains of homogeneous myelin ovoids were interfaced with proximal, preserved regions at sites of giant axonal swellings. Regeneration of myelinated axons also occurred during intoxication. Regenerating fibers wre composed of multiple, short, branched internodes which sometimes appeared multifocally swollen. Interfaces between regenerating and preserved portions of fibers were unswollen. Thick section studies showed that pronounced endoneurial edema accompanied fiber degeneration in peripheral nerve trunks. Ultrastructural studies revealed multifocal, giant axonal swellings containing masses of 10 nm neurofilaments and sometimes, clustered mitochondria, neurotubules and smooth endoplasmic reticulum. Enlarged granular mitochondria, interdigitated Schwann cell/axon networks and corrugated myelin sheaths were common findings. Dense granules, vesicles and hexagonal particles were also noted in the axoplasm. These findings provide new insights into the nature of the dying-back process: although there was a retrograde, temporal spread of axonal swelling up affected nerve trunks, axonal degeneration neither began in the nerve terminal nor spread seriatim centripetally along individual nerve fibers. The dying-back process was further examined in a companion study in this issue (32) which analyzed some of the factors determining the differential vulnerability of PNS and CNS fibers in animals intoxicated either with these neurotoxic hexacarbons or with acrylamide.", "contents": "Ultrastructural studies of the dying-back process. III. The evolution of experimental peripheral giant axonal degeneration. The spatio-temporal evolution of peripheral giant axonal degeneration has been studied in rats during the development of concurrent peripheral (PNS) and central (CNS) nervous system dying-back disease after chronic intoxication with the neurotoxic hexacarbons n-hexane (CH3CH2CH2CH2CH2CH3), methyl n-butyl ketone (MBK) (CH3COCH2CH2CH2CH3), or 2,5-hexanedione (CH3COCH2CH2CHOCH3), a neurotoxic metabolite of MBK. Each compound caused animals insidiously to develop identical, symmetrical peripheral neuropathies characterized by eversion and drop of hindfeet, inability to extend hindlimbs and upper extremity weakness. Teased fiber studies demonstrated that giant axonal swellings first developed on the proximal sides of multiple paranodes sited in distal, non-terminal regions of large myelinated fibers. Later, swellings developed at internodal sites. Smaller myelinated and unmyelinated fibers also underwent multifocal, giant axonal swelling. In affected myelinated fibers, swollen nodal and paranodal axons were frequently associated with retracted paranodal myelin sheaths. Adjacent distal internodes were attenuated and corrugated. Demyelinated paranodes apparently underwent local shrinkage and remyelination before complete distal fiber breakdown commenced. The proximal limits of chains of homogeneous myelin ovoids were interfaced with proximal, preserved regions at sites of giant axonal swellings. Regeneration of myelinated axons also occurred during intoxication. Regenerating fibers wre composed of multiple, short, branched internodes which sometimes appeared multifocally swollen. Interfaces between regenerating and preserved portions of fibers were unswollen. Thick section studies showed that pronounced endoneurial edema accompanied fiber degeneration in peripheral nerve trunks. Ultrastructural studies revealed multifocal, giant axonal swellings containing masses of 10 nm neurofilaments and sometimes, clustered mitochondria, neurotubules and smooth endoplasmic reticulum. Enlarged granular mitochondria, interdigitated Schwann cell/axon networks and corrugated myelin sheaths were common findings. Dense granules, vesicles and hexagonal particles were also noted in the axoplasm. These findings provide new insights into the nature of the dying-back process: although there was a retrograde, temporal spread of axonal swelling up affected nerve trunks, axonal degeneration neither began in the nerve terminal nor spread seriatim centripetally along individual nerve fibers. The dying-back process was further examined in a companion study in this issue (32) which analyzed some of the factors determining the differential vulnerability of PNS and CNS fibers in animals intoxicated either with these neurotoxic hexacarbons or with acrylamide."}
{"id": "PMID:190358", "title": "Ultrastructural studies of the dying-back process. IV. Differential vulnerability of PNS and CNS fibers in experimental central-peripheral distal axonopathies.", "content": "A companion paper in this issue (46) described the evolution of peripheral nervous system dying-back disease of the giant axonal type in animals chronically intoxicated with the neurotoxic hexacarbons n-hexane (CH3CH2CH2CH2CH2CH3), methyl n-butyl ketone or MBK (CH3COCH2CH2CH2CH3), and 2,5-hexanedione (CH3COCH2CH2COCH3). The present study compares the distribution and pattern of peripheral (PNS) and central nervous system (CNS) dying-back disease produced by these three neurotoxic hexacarbons with that produced by acrylamide (CH2CHCONH2), and, in addition, employs these compounds to address unresolved issues in the dying-back process. In the PNS, large myelinated fibers in tibial nerve branches supplying calf muscles were especially sensitive in rats intoxicated with hexacarbons. These nerve branches and sensory plantar nerves in the hindfeet were equally vulnerable in acrylamide-treated rats. In both conditions, fibers located at these sites commenced degeneration before the distal regions of much longer and smaller diameter nerve fibers in nerve branches supplying the flexor digitorum brevis muscle and, in rats intoxicated with hexacarbons, before equivalent regions of plantar sensory branches to the digits. Pacinian corpuscles sited in the hindfeet of intoxicated cats were much less vulnerable to MBK than to acrylamide. Rats and cats intoxicated with hexacarbons displayed giant axonal swellings in vulnerable regions of the PNS degeneration in these animals was accompanied by pronounced endoneurial edema. In the CNS, rostral regions of long, ascending tracts (dorso-spino-cerebellar, gracile and, later, the cuneate) and the caudal end of long, descending tracts (lateral colums, ventrolateral and ventromedial tracts) of hexacarbon-treated animals were especially vulnerable. After prolonged intoxication of cats with MBK, giant axonal swelling was also found in preterminal and terminal axons in Rexed laminae V-VII at spinal levels C4 through S3-Neurofilament proliferation without giant axonal swelling was seen in CNS fibers of rats intoxicated with acrylamide. Taken in concert, the findings underline the importance of axon diameter and length in determining the hierarchy of fiber vulnerability and indicate the common sensitivity of selected regions of the PNS and CNS. The term central-peripheral distal axonopathy is introduced to emphasize the widespread, distal distribution of disease in these and in similar experimental conditions. It is suggested that certain human neuropathies (toxic, nutritional, uremic, diabetic and some hereditary polyneuropathies, and the neuropathy associated with multiple myeloma) are additional examples of central-peripheral distal axonopathies.", "contents": "Ultrastructural studies of the dying-back process. IV. Differential vulnerability of PNS and CNS fibers in experimental central-peripheral distal axonopathies. A companion paper in this issue (46) described the evolution of peripheral nervous system dying-back disease of the giant axonal type in animals chronically intoxicated with the neurotoxic hexacarbons n-hexane (CH3CH2CH2CH2CH2CH3), methyl n-butyl ketone or MBK (CH3COCH2CH2CH2CH3), and 2,5-hexanedione (CH3COCH2CH2COCH3). The present study compares the distribution and pattern of peripheral (PNS) and central nervous system (CNS) dying-back disease produced by these three neurotoxic hexacarbons with that produced by acrylamide (CH2CHCONH2), and, in addition, employs these compounds to address unresolved issues in the dying-back process. In the PNS, large myelinated fibers in tibial nerve branches supplying calf muscles were especially sensitive in rats intoxicated with hexacarbons. These nerve branches and sensory plantar nerves in the hindfeet were equally vulnerable in acrylamide-treated rats. In both conditions, fibers located at these sites commenced degeneration before the distal regions of much longer and smaller diameter nerve fibers in nerve branches supplying the flexor digitorum brevis muscle and, in rats intoxicated with hexacarbons, before equivalent regions of plantar sensory branches to the digits. Pacinian corpuscles sited in the hindfeet of intoxicated cats were much less vulnerable to MBK than to acrylamide. Rats and cats intoxicated with hexacarbons displayed giant axonal swellings in vulnerable regions of the PNS degeneration in these animals was accompanied by pronounced endoneurial edema. In the CNS, rostral regions of long, ascending tracts (dorso-spino-cerebellar, gracile and, later, the cuneate) and the caudal end of long, descending tracts (lateral colums, ventrolateral and ventromedial tracts) of hexacarbon-treated animals were especially vulnerable. After prolonged intoxication of cats with MBK, giant axonal swelling was also found in preterminal and terminal axons in Rexed laminae V-VII at spinal levels C4 through S3-Neurofilament proliferation without giant axonal swelling was seen in CNS fibers of rats intoxicated with acrylamide. Taken in concert, the findings underline the importance of axon diameter and length in determining the hierarchy of fiber vulnerability and indicate the common sensitivity of selected regions of the PNS and CNS. The term central-peripheral distal axonopathy is introduced to emphasize the widespread, distal distribution of disease in these and in similar experimental conditions. It is suggested that certain human neuropathies (toxic, nutritional, uremic, diabetic and some hereditary polyneuropathies, and the neuropathy associated with multiple myeloma) are additional examples of central-peripheral distal axonopathies."}
{"id": "PMID:190362", "title": "Superficial temporal-middle cerebral artery anastomosis associated with glioblastoma multiforme.", "content": "The authors report a case in which glioblastoma multiforme was intimately associated with a surgical anastomosis of the superficial temporal artery to a branch of the middle cerebral artery.", "contents": "Superficial temporal-middle cerebral artery anastomosis associated with glioblastoma multiforme. The authors report a case in which glioblastoma multiforme was intimately associated with a surgical anastomosis of the superficial temporal artery to a branch of the middle cerebral artery."}
{"id": "PMID:190363", "title": "Technetium-99m-pyrophosphate bone scans in hyperparathyroidism.", "content": "Most patients with primary hyperparathyroidism have normal 5-hr bone-to-soft-tissue ratios for 99MTc-pyrophosphate. In contrast, all five patients with advanced secondary hyperparathyroidism in this study showed significant (p less than 0.001) increases of bone uptake. In the early period after parathyroidectomy, there was no quantitative or qualitative change in uptake. A limited decrease of bone uptake was observed only after prolonged periods of observation. In itself, parathyroid activity seems to have little direct influence on bone uptake of 99MTc-pyrophosphate.", "contents": "Technetium-99m-pyrophosphate bone scans in hyperparathyroidism. Most patients with primary hyperparathyroidism have normal 5-hr bone-to-soft-tissue ratios for 99MTc-pyrophosphate. In contrast, all five patients with advanced secondary hyperparathyroidism in this study showed significant (p less than 0.001) increases of bone uptake. In the early period after parathyroidectomy, there was no quantitative or qualitative change in uptake. A limited decrease of bone uptake was observed only after prolonged periods of observation. In itself, parathyroid activity seems to have little direct influence on bone uptake of 99MTc-pyrophosphate."}
{"id": "PMID:190359", "title": "An ultrastructural study of chronic sodium cyanate-indiuced neuropathy.", "content": "Fifteen rats were given a sodium cyanate-rich diet for 18 months and at the end of that period, all of them had developed motor weakness and were perfused for ultrastructural study. A peripheral neuropathy involving mostly the roots and sciatic nerves was found and the main ultrastructural lesion was vacuolization of myelin. There was marked distinction of the myelin sheaths and phagocytosis of myelin. Axoplasmic changes were minimal and consisted of accumulation of glycogen within vacuoles. Invaginations of adaxonal Schwann cell membranes and axolemma forming loops and separate chambers were also present. There was active participation of macrophages in the splitting of myelin as well as in phagocytosis of myelin remnants. There was evidence of remyelination with the toxic damage. We concluded that cyanate induced neuropathy is due mostly to a myelinotoxic effect of the drug, although parallel but less intense axonal damage cannot be excluded.", "contents": "An ultrastructural study of chronic sodium cyanate-indiuced neuropathy. Fifteen rats were given a sodium cyanate-rich diet for 18 months and at the end of that period, all of them had developed motor weakness and were perfused for ultrastructural study. A peripheral neuropathy involving mostly the roots and sciatic nerves was found and the main ultrastructural lesion was vacuolization of myelin. There was marked distinction of the myelin sheaths and phagocytosis of myelin. Axoplasmic changes were minimal and consisted of accumulation of glycogen within vacuoles. Invaginations of adaxonal Schwann cell membranes and axolemma forming loops and separate chambers were also present. There was active participation of macrophages in the splitting of myelin as well as in phagocytosis of myelin remnants. There was evidence of remyelination with the toxic damage. We concluded that cyanate induced neuropathy is due mostly to a myelinotoxic effect of the drug, although parallel but less intense axonal damage cannot be excluded."}
{"id": "PMID:190364", "title": "Technetium-99m-Sn-pyrophosphate pharmaco-kinetics and bone image changes in parathyroid disease.", "content": "Skeletal abnormalities in 12 patients with primary hyperparathyroidism, five patients with pseudohypoparathyroidism, and three patients with hypoparathyroidism were studied to compare the diagnostic sensitivity of bone radiologic examination to that of radionuclide studies using 99mTc-Sn-pyrophosphate (99mTc-PPi) a skeletal-seeking radiopharmaceutical. The results were compared with bone mineral content as measrued by the Norland--Cameron densitometer. Kinetic data of the blood disappearance and plasma clearance of 99mTc-PPi were obtained and compared with data of control subjects without evidence of parathyroid disease. Bone imaging with 99mTc-PPi may be more sensitive than routine skeletal radiographs and bone mineral analysis for the evaluation of skeletal abnormalities in patients with parathyroid disfunction. The enhanced plasma clearance of the tracer observed in patients with primary hyperparathyroidism may reflect the direct effect of excessive parathyroid hormone on the renal handling of 99mTc-Sn-pyrophosphate.", "contents": "Technetium-99m-Sn-pyrophosphate pharmaco-kinetics and bone image changes in parathyroid disease. Skeletal abnormalities in 12 patients with primary hyperparathyroidism, five patients with pseudohypoparathyroidism, and three patients with hypoparathyroidism were studied to compare the diagnostic sensitivity of bone radiologic examination to that of radionuclide studies using 99mTc-Sn-pyrophosphate (99mTc-PPi) a skeletal-seeking radiopharmaceutical. The results were compared with bone mineral content as measrued by the Norland--Cameron densitometer. Kinetic data of the blood disappearance and plasma clearance of 99mTc-PPi were obtained and compared with data of control subjects without evidence of parathyroid disease. Bone imaging with 99mTc-PPi may be more sensitive than routine skeletal radiographs and bone mineral analysis for the evaluation of skeletal abnormalities in patients with parathyroid disfunction. The enhanced plasma clearance of the tracer observed in patients with primary hyperparathyroidism may reflect the direct effect of excessive parathyroid hormone on the renal handling of 99mTc-Sn-pyrophosphate."}
{"id": "PMID:190365", "title": "Rectal perchlorate for unconscious patients prior to brain scintigraphy with pertechnetate: concise communication.", "content": "Patients undergoing brain scintigraphy with pertechnetate are frequently premedicated with oral perchlorate. However, the oral route is difficult to employ in unconscious or uncooperative patients or when oral intake is restricted. In such situations, rectal administration of sodium perchlorate dissolved in water is an effective alternative to oral administration.", "contents": "Rectal perchlorate for unconscious patients prior to brain scintigraphy with pertechnetate: concise communication. Patients undergoing brain scintigraphy with pertechnetate are frequently premedicated with oral perchlorate. However, the oral route is difficult to employ in unconscious or uncooperative patients or when oral intake is restricted. In such situations, rectal administration of sodium perchlorate dissolved in water is an effective alternative to oral administration."}
{"id": "PMID:190366", "title": "Aortic aneurysm detected by 99mTc-pyrophosphate imaging: case report.", "content": "An example of aneurysmal concentration of 99mTc-pyrophosphate (Tc-PPi) is described. An abdominal aortic aneurysm was suspected when a rectilinear bone scan showed an abnormal paraspinal area of activity. The aneurysm was confirmed by ultrasonic examination. Conventional radiographic examination failed to reveal calcification within the aneurysm. Aneurysmal concentration of Tc-PPi should be considered in patients showing abnormal radioactivity in the region of vascular structures on radionuclide bone images.", "contents": "Aortic aneurysm detected by 99mTc-pyrophosphate imaging: case report. An example of aneurysmal concentration of 99mTc-pyrophosphate (Tc-PPi) is described. An abdominal aortic aneurysm was suspected when a rectilinear bone scan showed an abnormal paraspinal area of activity. The aneurysm was confirmed by ultrasonic examination. Conventional radiographic examination failed to reveal calcification within the aneurysm. Aneurysmal concentration of Tc-PPi should be considered in patients showing abnormal radioactivity in the region of vascular structures on radionuclide bone images."}
{"id": "PMID:190369", "title": "Studies of anabolic steroids. VI. Effect of prolonged administration of oxandrolone on growth in children and adolescents with gonadal dysgenesis.", "content": "Twenty-five patients with Turner Syndrome were treated with oxandrolone for six or more months. Mean growth velocity for the first year of treatment was significantly greater than pretreatment control growth velocity. Overall, there was no excessive skeletal maturation. Mean \"final\" height in nine XO patients (146.4 cm) was significantly greater than mean adult height of an estrogen-treated control group (140.3 cm), while that for five mosaic patients (148.2 cm) was not significantly different from a mean untreated mosaic adult height (145.2 cm).", "contents": "Studies of anabolic steroids. VI. Effect of prolonged administration of oxandrolone on growth in children and adolescents with gonadal dysgenesis. Twenty-five patients with Turner Syndrome were treated with oxandrolone for six or more months. Mean growth velocity for the first year of treatment was significantly greater than pretreatment control growth velocity. Overall, there was no excessive skeletal maturation. Mean \"final\" height in nine XO patients (146.4 cm) was significantly greater than mean adult height of an estrogen-treated control group (140.3 cm), while that for five mosaic patients (148.2 cm) was not significantly different from a mean untreated mosaic adult height (145.2 cm)."}
{"id": "PMID:190373", "title": "Lid lesions of childhood: a histopathologic survey at the Wilmer Institute (1923-1974).", "content": "This study reports 398 excised eyelid lesions in 385 children from birth through age 15. This study analyzes and discusses the clinical and histological features of the 34 types of lesions which were encountered. This tabulation serves as a guide to the physician when confronted with lid lesions in children as to the types of lesions which may be found. More importantly, however, this study is the first comprehensive clinco-pathologic evaluation of eyelid lesions in children, a topic which had previously been written and discussed in a fragmentary manner. This study analyzes data from the Wilmer Institute during 1923-1974.", "contents": "Lid lesions of childhood: a histopathologic survey at the Wilmer Institute (1923-1974). This study reports 398 excised eyelid lesions in 385 children from birth through age 15. This study analyzes and discusses the clinical and histological features of the 34 types of lesions which were encountered. This tabulation serves as a guide to the physician when confronted with lid lesions in children as to the types of lesions which may be found. More importantly, however, this study is the first comprehensive clinco-pathologic evaluation of eyelid lesions in children, a topic which had previously been written and discussed in a fragmentary manner. This study analyzes data from the Wilmer Institute during 1923-1974."}
{"id": "PMID:190374", "title": "Unusual eyelid involvement in tuberous sclerosis.", "content": "A two-week-old male infant had a nodular salmon-colored lesion on his right lower eyelid and hypopigmented mascular lesions on the abdomen and right thigh since birth. At five months of age he developed a generalized seizure disorder. Histologic examination of the eyelid lesion revealed an angiofibroma, which was an unusual initial site of involvement in tuberous sclerosis.", "contents": "Unusual eyelid involvement in tuberous sclerosis. A two-week-old male infant had a nodular salmon-colored lesion on his right lower eyelid and hypopigmented mascular lesions on the abdomen and right thigh since birth. At five months of age he developed a generalized seizure disorder. Histologic examination of the eyelid lesion revealed an angiofibroma, which was an unusual initial site of involvement in tuberous sclerosis."}
{"id": "PMID:190376", "title": "Potential long acting opiate antagonists: preparation, pharmacological activity, and opiate-receptor binding of N-substituted 2'-hydroxy-5-methyl-9 alpha-propyl-6,7-benzomorphans.", "content": "A homologous series of N-substituted 2'-hydroxy-5-methyl-9 alpha-propyl-6,7-benzomorphans (hydrogen to octyl inclusive, allyl, and cyclopropylmethyl) was prepared. In contradistinction to the normetazocine, normorphine, and (-)-3-hydroxymorphinan series, the N-pentyl and N-hexyl derivatives do not have the analgesic potency of the parent N-methyl compound; instead, they are narcotic antagonists with a long duration of action. All of the N-substituted 9 alpha-propylbenzomorphans, except for methyl, heptyl, and octyl, have antagonist activity. The receptor binding constants of the N-alkyl compounds are uniformly two- to threefold lower than those of the N-substituted normetazocines.", "contents": "Potential long acting opiate antagonists: preparation, pharmacological activity, and opiate-receptor binding of N-substituted 2'-hydroxy-5-methyl-9 alpha-propyl-6,7-benzomorphans. A homologous series of N-substituted 2'-hydroxy-5-methyl-9 alpha-propyl-6,7-benzomorphans (hydrogen to octyl inclusive, allyl, and cyclopropylmethyl) was prepared. In contradistinction to the normetazocine, normorphine, and (-)-3-hydroxymorphinan series, the N-pentyl and N-hexyl derivatives do not have the analgesic potency of the parent N-methyl compound; instead, they are narcotic antagonists with a long duration of action. All of the N-substituted 9 alpha-propylbenzomorphans, except for methyl, heptyl, and octyl, have antagonist activity. The receptor binding constants of the N-alkyl compounds are uniformly two- to threefold lower than those of the N-substituted normetazocines."}
{"id": "PMID:190377", "title": "Effects of acute and chronic ethanol administration and withdrawal on adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate levels in the rat brain.", "content": "The effect of ethanol on cyclic nucleotide levels was investigated in male Sprague-Dawley rats. The rats were sacrificed by microwave irradiation, the brains were divided into four areas, and cyclic nucleotides were measured by radioimmunoassays. Administration of a single dose of ethanol per os produced a dose-dependent decrease of adenosine 3':5'-monophosphate (cyclic AMP) in cerebral cortex, cerebellum, pons and medulla oblongata while guanosine 3':5'-monophosphate (cyclic GMP) was decreased in all brain areas. Dependence on ethanol was induced by three daily administrations of ethanol p.o. for 7 days. The last dose of ethanol did not produce any decrease of cyclic AMP levels while the decrease of cyclic GMP levels was still present. During ethanol withdrawal cyclic AMP levels increased in cerebral cortex, pons and medulla oblongata and did not change in cerebellum. Changes of cyclic AMP in subcortex were more complex. Cyclic GMP levels increased during ethanol withdrawal in cerebellum, pons and medulla oblongata and did not change in cerebral cortex and subcortex. These results indicate that changes of cyclic nucleotides might participate in the mechanism of ethanol dependence and withdrawal.", "contents": "Effects of acute and chronic ethanol administration and withdrawal on adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate levels in the rat brain. The effect of ethanol on cyclic nucleotide levels was investigated in male Sprague-Dawley rats. The rats were sacrificed by microwave irradiation, the brains were divided into four areas, and cyclic nucleotides were measured by radioimmunoassays. Administration of a single dose of ethanol per os produced a dose-dependent decrease of adenosine 3':5'-monophosphate (cyclic AMP) in cerebral cortex, cerebellum, pons and medulla oblongata while guanosine 3':5'-monophosphate (cyclic GMP) was decreased in all brain areas. Dependence on ethanol was induced by three daily administrations of ethanol p.o. for 7 days. The last dose of ethanol did not produce any decrease of cyclic AMP levels while the decrease of cyclic GMP levels was still present. During ethanol withdrawal cyclic AMP levels increased in cerebral cortex, pons and medulla oblongata and did not change in cerebellum. Changes of cyclic AMP in subcortex were more complex. Cyclic GMP levels increased during ethanol withdrawal in cerebellum, pons and medulla oblongata and did not change in cerebral cortex and subcortex. These results indicate that changes of cyclic nucleotides might participate in the mechanism of ethanol dependence and withdrawal."}
{"id": "PMID:190378", "title": "The presynaptic site of action of norepinephrine in the superior cervical ganglion of guinea pig.", "content": "Supramaximal preganglionic volleys did not elicit detectable postsynaptic potential in the curare-treated superior cervical ganglion cell of the guinea pig whereas, a tetanic stimulation (10-30 Hz, 1-5 seconds) consistently evoked a monophasic depolarizing potential resembling the slow excitatory postsynaptic potential. The depolarizing potential was not preceded by a detectable hyperpolarization. In non-curare-treated preparations, norepinephrine in concentrations of 1 to 10 muM consistently and reversibly suppressed the fast excitatory postsynaptic potential elicited by submaximal preganglionic stimulation without appreciably affecting the resting membrane potential, the total membrane resistance or the cell membrane excitability. Pretreating the ganglion with phenoxybenzamine (10 muM) completely prevented, whereas propranolol (30 muM) failed to antagonize, the ganglionic depressant action of norepinephrine. The amplitude and time course of the iontophoretically induced acetylcholine potential were not significantly altered by norepinephrine in concentrations which markedly attenuated the response of the fast excitatory postsynaptic potential. The frequency but not the amplitude of the miniature excitatory postsynaptic potentials was significantly reduced by norepinephrine (1-10 muM). These results demonstrate that norepinephrine inhibits ganglionic transmission in the guinea pig principally by reducing the output of acetylcholine from the presynaptic nerve terminals. These data are discussed with respect to their relation to the presence in the guinea pig superior cervical ganglion of norepinephrine-containing small intensely fluorescent cells which are not connected synaptically with the postganglionic neurons.", "contents": "The presynaptic site of action of norepinephrine in the superior cervical ganglion of guinea pig. Supramaximal preganglionic volleys did not elicit detectable postsynaptic potential in the curare-treated superior cervical ganglion cell of the guinea pig whereas, a tetanic stimulation (10-30 Hz, 1-5 seconds) consistently evoked a monophasic depolarizing potential resembling the slow excitatory postsynaptic potential. The depolarizing potential was not preceded by a detectable hyperpolarization. In non-curare-treated preparations, norepinephrine in concentrations of 1 to 10 muM consistently and reversibly suppressed the fast excitatory postsynaptic potential elicited by submaximal preganglionic stimulation without appreciably affecting the resting membrane potential, the total membrane resistance or the cell membrane excitability. Pretreating the ganglion with phenoxybenzamine (10 muM) completely prevented, whereas propranolol (30 muM) failed to antagonize, the ganglionic depressant action of norepinephrine. The amplitude and time course of the iontophoretically induced acetylcholine potential were not significantly altered by norepinephrine in concentrations which markedly attenuated the response of the fast excitatory postsynaptic potential. The frequency but not the amplitude of the miniature excitatory postsynaptic potentials was significantly reduced by norepinephrine (1-10 muM). These results demonstrate that norepinephrine inhibits ganglionic transmission in the guinea pig principally by reducing the output of acetylcholine from the presynaptic nerve terminals. These data are discussed with respect to their relation to the presence in the guinea pig superior cervical ganglion of norepinephrine-containing small intensely fluorescent cells which are not connected synaptically with the postganglionic neurons."}
{"id": "PMID:190379", "title": "Cardiac histamine receptors: differences between left and right atria and right ventricle.", "content": "Histamine can stiumulate the heart by directly interacting with cardiac histamine receptors. In the present study we have investigated the cardiac effects of histamine, 4-methylhistamine (a specific H2-receptor agonist) and 2-pyridylethylamine PEA, a specific H1-receptor agonist] on spontaneously beating right atria and electrically driven left atria and right ventricle strips of the guinea pig. Left atria were driven at 1 Hz and right ventricle strips at 2.5 Hz and at twice the threshold voltage. Histamine and PEA produced a dose-dependent positive inotropic effect on the left atria. The dose-response curves were shifted to the right in a parallel fashion by promethazine (3 x 10(-6)M)+... Burimamide did not affect either dose-response curve. Histamine and 4-methylhistamine had a positive chromnotropic effect on right atria and a positive inotropic effect on right ventricle strips.", "contents": "Cardiac histamine receptors: differences between left and right atria and right ventricle. Histamine can stiumulate the heart by directly interacting with cardiac histamine receptors. In the present study we have investigated the cardiac effects of histamine, 4-methylhistamine (a specific H2-receptor agonist) and 2-pyridylethylamine PEA, a specific H1-receptor agonist] on spontaneously beating right atria and electrically driven left atria and right ventricle strips of the guinea pig. Left atria were driven at 1 Hz and right ventricle strips at 2.5 Hz and at twice the threshold voltage. Histamine and PEA produced a dose-dependent positive inotropic effect on the left atria. The dose-response curves were shifted to the right in a parallel fashion by promethazine (3 x 10(-6)M)+... Burimamide did not affect either dose-response curve. Histamine and 4-methylhistamine had a positive chromnotropic effect on right atria and a positive inotropic effect on right ventricle strips."}
{"id": "PMID:190382", "title": "The distribution of GABA sensitivity on crayfish muscle receptor organs.", "content": "1. The effectiveness of inhibition of gamma-aminobutyric acid (GABA) at various points on crayfish abdominal muscle receptor organs (MROs) was investigated by iontophoretic methods that have a spatial resolution of 8 mum. 2. The MROs in the rostral abdominal segments, which receive inhibitory innervation, were always strongly inhibited by focal iontophoretic application of GABA; MROs in the 6th abdominal segment, which do not receive inhibitory innervation, were usually not strongly inhibited. 3. In the rostral MROs, the magnitude of GABA current necessary to abolish stretch induced impulses was least for dendritic points; it increased as a function of distance from the dendrites, over an area extending from the receptor muscle to a point on the axon 200 mum from the cell body. 4. Outward currrents from NaCl-filled micropipettes had no effect on impulse production when applied to the dendritic region of rostral MROs, but could produce transient inhibition of impulses when applied to the axon. 5. It is suggested that a high degree of GABA sensitivity is localized to the rostral MRO dendrites, where inhibitory synapses are most numerous.", "contents": "The distribution of GABA sensitivity on crayfish muscle receptor organs. 1. The effectiveness of inhibition of gamma-aminobutyric acid (GABA) at various points on crayfish abdominal muscle receptor organs (MROs) was investigated by iontophoretic methods that have a spatial resolution of 8 mum. 2. The MROs in the rostral abdominal segments, which receive inhibitory innervation, were always strongly inhibited by focal iontophoretic application of GABA; MROs in the 6th abdominal segment, which do not receive inhibitory innervation, were usually not strongly inhibited. 3. In the rostral MROs, the magnitude of GABA current necessary to abolish stretch induced impulses was least for dendritic points; it increased as a function of distance from the dendrites, over an area extending from the receptor muscle to a point on the axon 200 mum from the cell body. 4. Outward currrents from NaCl-filled micropipettes had no effect on impulse production when applied to the dendritic region of rostral MROs, but could produce transient inhibition of impulses when applied to the axon. 5. It is suggested that a high degree of GABA sensitivity is localized to the rostral MRO dendrites, where inhibitory synapses are most numerous."}
{"id": "PMID:190383", "title": "Cyclic adenosine 3', 5'-monophosphate in cerebrospinal fluid during thermoregulation and fever.", "content": "1. Samples of cerebrospinal fluid (c.s.f.) have been taken from the cisterna magna of unanaesthetized cats, whilst rectal temperature was recorded, during exposure of the animals to various ambient temperatures and during fever induced by pyrogen. The concentration of adenosine 3', 5'-monophosphate (cyclic AMP) in samples of c.s.f. has been assayed. 2. Cats exposed to low ambient temperatures (-2 to +2 degrees C) for 3 h maintained body temperature by both behavioural and autonomic heat gain activity. Exposure of cats to high ambient temperatures (44 - 45 degrees C) for 3.5 h caused a rise in body temperatures of about 2.5 degrees C, despite behavioural and autonomic heat loss activity. Neither cold nor heat stress had a significant effect on c.s.f. cyclic AMP. 3. Fever induced by intravenous Shigella dysenteriae (2 and 20 mug/kg) was associated with a dose-related increase in the concentration of cyclic AMP in c.s.f. Paracetamol (75 mg/kg) injected I.P. before the onset of fever, suppressed the increase in both temperature and c.s.f. cyclic AMP in response to pyrogen. Paracetamol (50 and 100 mg/kg), injected after the onset of fever, caused a fall in temperature, which was not associated with a decrease in the concentration of cyclic AMP in c.s.f. 4. Fever induced in cats by intravenous Shigella dysenteriae (20 mug/kg) was associated with an increase in the concentration of cyclic AMP in plasma as well as in c.s.f. 5. The sodium salt of cyclic AMP (0.1-10 mg/kg) injected I.V. into unanaesthetized cats caused a dose-related hypothermia, which was associated with autonomic heat loss activity and a dose-related increase in the concentration of cyclic AMP in cisternal c.s.f., which was not mimicked by adenosine. 6. It is concluded that the raised concentrations of cyclic AMP in c.s.f., in response to pyrogen I.V., do not mediate fever in the cat and that the concentration of cyclic AMP in cisternal c.s.f. may be affected by changes in the plasma concentration of the nucleotide.", "contents": "Cyclic adenosine 3', 5'-monophosphate in cerebrospinal fluid during thermoregulation and fever. 1. Samples of cerebrospinal fluid (c.s.f.) have been taken from the cisterna magna of unanaesthetized cats, whilst rectal temperature was recorded, during exposure of the animals to various ambient temperatures and during fever induced by pyrogen. The concentration of adenosine 3', 5'-monophosphate (cyclic AMP) in samples of c.s.f. has been assayed. 2. Cats exposed to low ambient temperatures (-2 to +2 degrees C) for 3 h maintained body temperature by both behavioural and autonomic heat gain activity. Exposure of cats to high ambient temperatures (44 - 45 degrees C) for 3.5 h caused a rise in body temperatures of about 2.5 degrees C, despite behavioural and autonomic heat loss activity. Neither cold nor heat stress had a significant effect on c.s.f. cyclic AMP. 3. Fever induced by intravenous Shigella dysenteriae (2 and 20 mug/kg) was associated with a dose-related increase in the concentration of cyclic AMP in c.s.f. Paracetamol (75 mg/kg) injected I.P. before the onset of fever, suppressed the increase in both temperature and c.s.f. cyclic AMP in response to pyrogen. Paracetamol (50 and 100 mg/kg), injected after the onset of fever, caused a fall in temperature, which was not associated with a decrease in the concentration of cyclic AMP in c.s.f. 4. Fever induced in cats by intravenous Shigella dysenteriae (20 mug/kg) was associated with an increase in the concentration of cyclic AMP in plasma as well as in c.s.f. 5. The sodium salt of cyclic AMP (0.1-10 mg/kg) injected I.V. into unanaesthetized cats caused a dose-related hypothermia, which was associated with autonomic heat loss activity and a dose-related increase in the concentration of cyclic AMP in cisternal c.s.f., which was not mimicked by adenosine. 6. It is concluded that the raised concentrations of cyclic AMP in c.s.f., in response to pyrogen I.V., do not mediate fever in the cat and that the concentration of cyclic AMP in cisternal c.s.f. may be affected by changes in the plasma concentration of the nucleotide."}
{"id": "PMID:190384", "title": "A quantitative analysis of local anaesthetic alteration of miniature end-plate currents and end-plate current fluctuations.", "content": "1. The effect of the local anaesthetic QX222 on the kinetics of miniature end-plate currents (m.e.p.c.s) and acetylcholine (ACh) induced end-plate current (e.p.c) fluctuations was studied in voltage-clamped frog cutaneous pectoris neuromuscular junctions made visible with Nomarski differential interference contrast optics. 2. In Ringer solution the m.e.p.c.s decayed with a single exponential time course and the e.p.c. fluctuation spectra were characterized by single Lorentzian functions, with the spectral cut-off frequency well predicted by the m.e.p.c. decay rate. 3. In the presence of 0-1-0-5 mm QX222 at-50 to -100 mV holding potential both the e.p.c. fluctuation spectrum and the m.e.p.c. decay consisted of a fast and a slow component, with the cut-off frequency of each spectral component predicted by the decay rate of the corresponding constituent of the m.e.p.c. 4. Hyperpolarization increased the decay rate and relative amplitude of the fast component of the m.e.p.c. and decreased the decay rate of the slow m.e.p.c. component. 5. With 0-05 mm QX222 and -70 mV holding potential the m.e.p.c.s. and e.p.c. fluctuation spectra consisted of three components. The third component of the m.e.p.c. and e.p.c. spectra had nearly the same decay rate and cut-off frequency as was found at the same end-plate under equivalent conditions before drug exposure. 6. The kinetic predictions of four different schemes for local anaesthetic action were compared with observed m.e.p.c.s. and e.p.c. fluctuations. 7. Schemes in which the local anaesthetic acted by creating two kinetically distinct populations of acetylcholine receptors or by interacting with ACh receptor to produce a biphasic exponential decay of the end-plate channel conductance did not accurately predict the e.p.c. fluctuation spectrum. 8. The variance of the e.p.c. fluctuations vanished at the reversal potential indicating that local anaesthetic action was not due to the presence of different ion selective end-plate channels. 9. QX222 action could be explained by alteration of the ACh receptors such that they sequentially c-hanged from one conductance state to another. A specific case in which QX222 binds to the ACh receptors in its open state creating a partially blocked state, was found to be the most parisimonious. 10. The conductance, gamma, of a single end-plate channel was estimated from e.p.c. fluctuations. In Ringer's solution gama = 24-4 +/- 1-2 (s.d.) pmho. In the presence of 0-1 mm to 0-5 mm QX222 the effective single channel conductance, gamma, varied from 14-2 to 1-39 pmho. 11. gamma decreased with increased local anesthetic concentration, hyperpolarization, or decreased temperature. The variation in gamma is thought to reflect the dependence on the experimental conditions of the relative probability that the ACh receptors is in an open vs a partially blocked state.", "contents": "A quantitative analysis of local anaesthetic alteration of miniature end-plate currents and end-plate current fluctuations. 1. The effect of the local anaesthetic QX222 on the kinetics of miniature end-plate currents (m.e.p.c.s) and acetylcholine (ACh) induced end-plate current (e.p.c) fluctuations was studied in voltage-clamped frog cutaneous pectoris neuromuscular junctions made visible with Nomarski differential interference contrast optics. 2. In Ringer solution the m.e.p.c.s decayed with a single exponential time course and the e.p.c. fluctuation spectra were characterized by single Lorentzian functions, with the spectral cut-off frequency well predicted by the m.e.p.c. decay rate. 3. In the presence of 0-1-0-5 mm QX222 at-50 to -100 mV holding potential both the e.p.c. fluctuation spectrum and the m.e.p.c. decay consisted of a fast and a slow component, with the cut-off frequency of each spectral component predicted by the decay rate of the corresponding constituent of the m.e.p.c. 4. Hyperpolarization increased the decay rate and relative amplitude of the fast component of the m.e.p.c. and decreased the decay rate of the slow m.e.p.c. component. 5. With 0-05 mm QX222 and -70 mV holding potential the m.e.p.c.s. and e.p.c. fluctuation spectra consisted of three components. The third component of the m.e.p.c. and e.p.c. spectra had nearly the same decay rate and cut-off frequency as was found at the same end-plate under equivalent conditions before drug exposure. 6. The kinetic predictions of four different schemes for local anaesthetic action were compared with observed m.e.p.c.s. and e.p.c. fluctuations. 7. Schemes in which the local anaesthetic acted by creating two kinetically distinct populations of acetylcholine receptors or by interacting with ACh receptor to produce a biphasic exponential decay of the end-plate channel conductance did not accurately predict the e.p.c. fluctuation spectrum. 8. The variance of the e.p.c. fluctuations vanished at the reversal potential indicating that local anaesthetic action was not due to the presence of different ion selective end-plate channels. 9. QX222 action could be explained by alteration of the ACh receptors such that they sequentially c-hanged from one conductance state to another. A specific case in which QX222 binds to the ACh receptors in its open state creating a partially blocked state, was found to be the most parisimonious. 10. The conductance, gamma, of a single end-plate channel was estimated from e.p.c. fluctuations. In Ringer's solution gama = 24-4 +/- 1-2 (s.d.) pmho. In the presence of 0-1 mm to 0-5 mm QX222 the effective single channel conductance, gamma, varied from 14-2 to 1-39 pmho. 11. gamma decreased with increased local anesthetic concentration, hyperpolarization, or decreased temperature. The variation in gamma is thought to reflect the dependence on the experimental conditions of the relative probability that the ACh receptors is in an open vs a partially blocked state."}
{"id": "PMID:190385", "title": "Dual effects of hemicholinium-3 at central cholinergic synapses.", "content": "1. Hemicholinium-3 (HC-3) has at least two presynaptic effects at cholinergic synapses between motor acon collaterals and spinal Renshaw cells, neither of which influenced non-cholinergic excitatory synapses on dorsal horn interneurones. 2. One, which occurred independently of repetitive activity of the synapses and which resulted in increased latency of synaptic excitation, presumably involved changes in the properties of presynaptic fibres and terminals which influenced transmitter release. 3. The other, which depended on continuous repetitive synaptic activity, was consistent with depletion by HC-3 of presynaptic stores of acetylcholine (ACh).", "contents": "Dual effects of hemicholinium-3 at central cholinergic synapses. 1. Hemicholinium-3 (HC-3) has at least two presynaptic effects at cholinergic synapses between motor acon collaterals and spinal Renshaw cells, neither of which influenced non-cholinergic excitatory synapses on dorsal horn interneurones. 2. One, which occurred independently of repetitive activity of the synapses and which resulted in increased latency of synaptic excitation, presumably involved changes in the properties of presynaptic fibres and terminals which influenced transmitter release. 3. The other, which depended on continuous repetitive synaptic activity, was consistent with depletion by HC-3 of presynaptic stores of acetylcholine (ACh)."}
{"id": "PMID:190401", "title": "Assay of pertussis vaccine toxicity by a rat-paw-oedema method.", "content": "A method is described of using the production of oedema in the foot pad of rats as an index of the ability of pertussis vaccines to cause local reactions. At a suitable time after the subcutaneous injection of the vaccine into hind paw of the rat, the foot is excised and weighed. The technique is reproducible and most useful for the detection of oedema produced by pertussis-vaccine components sensitive to heating at 80 degrees C for 30 min. Substances in pertussis vaccine that produce rat-paw oedema gave maximal reactions at 4 and 12 h. but were best differentiated 9 h after injection.", "contents": "Assay of pertussis vaccine toxicity by a rat-paw-oedema method. A method is described of using the production of oedema in the foot pad of rats as an index of the ability of pertussis vaccines to cause local reactions. At a suitable time after the subcutaneous injection of the vaccine into hind paw of the rat, the foot is excised and weighed. The technique is reproducible and most useful for the detection of oedema produced by pertussis-vaccine components sensitive to heating at 80 degrees C for 30 min. Substances in pertussis vaccine that produce rat-paw oedema gave maximal reactions at 4 and 12 h. but were best differentiated 9 h after injection."}
{"id": "PMID:190402", "title": "Experimental infection of monkeys with Herpesvirus suis (Aujeszky's-disease virus).", "content": "Monkeys were infected intranasally with Herpesvirus suis. After an incubation period of 7 to 13 days the animals became acutely ill and rapidly died. Clinical signs included salivation, incoordination, ataxia and epileptiform convulsions, but not pruritus. Histopathological changes were confined to the central nervous system, and consisted of destruction of neurones with the formation of intranuclear inclusion bodies, gliosis and perivascular cuffing. Virus was isolated from the brain and spinal cord in the later stages of the illness but neutralising antibodies were not detected in serum. The distribution of lesions indicated direct spread of virus from the inoculation site along cranial nerves to the brain.", "contents": "Experimental infection of monkeys with Herpesvirus suis (Aujeszky's-disease virus). Monkeys were infected intranasally with Herpesvirus suis. After an incubation period of 7 to 13 days the animals became acutely ill and rapidly died. Clinical signs included salivation, incoordination, ataxia and epileptiform convulsions, but not pruritus. Histopathological changes were confined to the central nervous system, and consisted of destruction of neurones with the formation of intranuclear inclusion bodies, gliosis and perivascular cuffing. Virus was isolated from the brain and spinal cord in the later stages of the illness but neutralising antibodies were not detected in serum. The distribution of lesions indicated direct spread of virus from the inoculation site along cranial nerves to the brain."}
{"id": "PMID:190403", "title": "Small virus particles in faeces of patients with infectious hepatitis (hepatitis A).", "content": "Forty-one faecal samples from infectious-hepatitis patients and their contacts were investigated for the presence of hepatitis-A-associated viral particles. Of these, 16 gave a positive result by immune electronmicroscopy or caesium-chloride density-gradient centrifugation. The latter method proved invaluable in detecting small numbers of virus particles. The particles found had buoyant density of 1-34-1-35 and a size range of 21-28 nm. Epidemiological evidence suggested that they might be the causative agent of hepatitis A.", "contents": "Small virus particles in faeces of patients with infectious hepatitis (hepatitis A). Forty-one faecal samples from infectious-hepatitis patients and their contacts were investigated for the presence of hepatitis-A-associated viral particles. Of these, 16 gave a positive result by immune electronmicroscopy or caesium-chloride density-gradient centrifugation. The latter method proved invaluable in detecting small numbers of virus particles. The particles found had buoyant density of 1-34-1-35 and a size range of 21-28 nm. Epidemiological evidence suggested that they might be the causative agent of hepatitis A."}
{"id": "PMID:190404", "title": "Agonist induced release of intracellular Ca2+ in the rabbit aorta.", "content": "The effects of hormonal agonists (norepinephrine, angiotensin, and histamine) on 45Ca efflux from the rabbit aorta were studied using a Ca-EGTA buffered efflux medium. Each caused a transient stimulation of efflux rate which probably reflected the release of an intracellular 45Ca store. The size of the stimulation of efflux correlated with the size of the initial rapid phase of contraction. The norepinephrine-sensitive intracellular Ca fraction was estimated to be greater than 21 mumoles/Kg wet tissue weight. This fraction is separate from intracellular Ca which is accumulated during relaxation. Evidence is presented for the lack of cyclic nucleotide involvement in the release of Ca2+, and possible alternative modes of coupling are discussed.", "contents": "Agonist induced release of intracellular Ca2+ in the rabbit aorta. The effects of hormonal agonists (norepinephrine, angiotensin, and histamine) on 45Ca efflux from the rabbit aorta were studied using a Ca-EGTA buffered efflux medium. Each caused a transient stimulation of efflux rate which probably reflected the release of an intracellular 45Ca store. The size of the stimulation of efflux correlated with the size of the initial rapid phase of contraction. The norepinephrine-sensitive intracellular Ca fraction was estimated to be greater than 21 mumoles/Kg wet tissue weight. This fraction is separate from intracellular Ca which is accumulated during relaxation. Evidence is presented for the lack of cyclic nucleotide involvement in the release of Ca2+, and possible alternative modes of coupling are discussed."}
{"id": "PMID:190406", "title": "Spin-label studies on rat liver and heart plasma membranes: do probe-probe interactions interfere with the measurement of membrane properties?", "content": "The structures of purified rat liver and heart plasma membranes were studied with the 5-nitroxide stearic acid spin probe, I(12,3). ESR spectra were recorded with a 50 gauss field sweep, and also with a new technique which \"expands\" the spectrum by (1) recording pairs of adjoining peaks with a smaller field sweep and (2) superposing the common peaks. The hyperfine splittings measured from the \"expanded\" spectra were significantly more precise than those obtained from the \"unexpanded\" spectra. Both procedures were used to study the effects of various I(12,3) probe concentrations on the spectra of liver and heart membranes, as well as the effects of temperature and CaCl2 additions on the spectra of liver membranes, and revealed the following: The polarity-corrected order parameters of liver (31 degrees) and heart (22 degrees) membranes were found to be independent of the probe concentration, if experimentally-determined low I(12,3)/lipid ratios were employed. The absence of obvious radical-interaction broadening in the unexpanded spectra indicated that \"intrinsic\" membrane properties may be measured at these low probe/lipid ratios. Here, \"intrinsic\" properties are defined as those which are measured when probe-probe interactions are negligible, and do not refer to membrane behavior in the absence of a perturbing spin label. At higher I(12,3)/lipid ratios, the order parameters of liver and heart membranes were found to substantially decrease with increasing probe concentration. The increase in the \"apparent\" fluidity of both membrane systems is attributed to enhanced radical interactions; however, an examination of these spectra (without reference to \"low\" probe concentration spectra) might incorrectly suggest that radical interactions were absent. For the membrane concentrations employed in these studies, the presence of \"liquid-lines\" (or \"fluid components\") in the unexpanded ESR spectra was a convenient marker of high probe concentrations. A thermotropic phase separation was observed in liver membranes between 19 degrees and 28 degrees. Addition of CaCl2 to liver plasma membrane [labelled with \"low\" I(12,3) concentrations] increased the rigidity of the membrane at 31 degrees and 37 degrees, without inducing a segregation of the probe in the bilayer. Previously reported data are discussed in relation to these results, and suggested minimal criteria for performing membrane spin label studies are included.", "contents": "Spin-label studies on rat liver and heart plasma membranes: do probe-probe interactions interfere with the measurement of membrane properties? The structures of purified rat liver and heart plasma membranes were studied with the 5-nitroxide stearic acid spin probe, I(12,3). ESR spectra were recorded with a 50 gauss field sweep, and also with a new technique which \"expands\" the spectrum by (1) recording pairs of adjoining peaks with a smaller field sweep and (2) superposing the common peaks. The hyperfine splittings measured from the \"expanded\" spectra were significantly more precise than those obtained from the \"unexpanded\" spectra. Both procedures were used to study the effects of various I(12,3) probe concentrations on the spectra of liver and heart membranes, as well as the effects of temperature and CaCl2 additions on the spectra of liver membranes, and revealed the following: The polarity-corrected order parameters of liver (31 degrees) and heart (22 degrees) membranes were found to be independent of the probe concentration, if experimentally-determined low I(12,3)/lipid ratios were employed. The absence of obvious radical-interaction broadening in the unexpanded spectra indicated that \"intrinsic\" membrane properties may be measured at these low probe/lipid ratios. Here, \"intrinsic\" properties are defined as those which are measured when probe-probe interactions are negligible, and do not refer to membrane behavior in the absence of a perturbing spin label. At higher I(12,3)/lipid ratios, the order parameters of liver and heart membranes were found to substantially decrease with increasing probe concentration. The increase in the \"apparent\" fluidity of both membrane systems is attributed to enhanced radical interactions; however, an examination of these spectra (without reference to \"low\" probe concentration spectra) might incorrectly suggest that radical interactions were absent. For the membrane concentrations employed in these studies, the presence of \"liquid-lines\" (or \"fluid components\") in the unexpanded ESR spectra was a convenient marker of high probe concentrations. A thermotropic phase separation was observed in liver membranes between 19 degrees and 28 degrees. Addition of CaCl2 to liver plasma membrane [labelled with \"low\" I(12,3) concentrations] increased the rigidity of the membrane at 31 degrees and 37 degrees, without inducing a segregation of the probe in the bilayer. Previously reported data are discussed in relation to these results, and suggested minimal criteria for performing membrane spin label studies are included."}
{"id": "PMID:190410", "title": "Isolation and characterization of a hormone-producing cell line from human small cell anaplastic carcinoma of the lung.", "content": "A continuous cell culture line was established from a bone marrow metastasis of small cell anaplastic carcinoma of the lung. The cultures were characterized by light and electron microscopy, and an unusual concentric arrangement of cells was observed, both in sectioned material from the patient's tumor and from the cell cultures. The cells had two types of specialized cell junctions and contained secretory-like granules of the type described in neuroendocrine cells. Lactic dehydrogenase isozyme patterns were the same as those observed in normal human serum, and the karyotype revealed the presence of several marker chromosomes. Vasopressin was present in the cells and secreted into the culture medium in the absence of neurophysin, as shown by the immunoperoxidase technique and radioimmunoassay. Oxytocin was also absent from cells.", "contents": "Isolation and characterization of a hormone-producing cell line from human small cell anaplastic carcinoma of the lung. A continuous cell culture line was established from a bone marrow metastasis of small cell anaplastic carcinoma of the lung. The cultures were characterized by light and electron microscopy, and an unusual concentric arrangement of cells was observed, both in sectioned material from the patient's tumor and from the cell cultures. The cells had two types of specialized cell junctions and contained secretory-like granules of the type described in neuroendocrine cells. Lactic dehydrogenase isozyme patterns were the same as those observed in normal human serum, and the karyotype revealed the presence of several marker chromosomes. Vasopressin was present in the cells and secreted into the culture medium in the absence of neurophysin, as shown by the immunoperoxidase technique and radioimmunoassay. Oxytocin was also absent from cells."}
{"id": "PMID:190411", "title": "Inhibition of glycolysis and interference with protein synthesis in hepatoma cells.", "content": "Ascites hepatoma cells grown in Wistar rats were incubated anaerobically in the absence of glucose or in the presence of both glucose and D(+)glucosamine, or monoiodoacetate, or NADH, which interfered with glycolysis at different steps and with different mechanisms: Under all these conditions the incorporation of amino acids into the proteins of hepatoma cells was severely reduced without any clear relationship to the degree of inhibition of glycolysis. The postmitochondrial supernatants showed defective incorporation only when obtained from cells incubated in the absence of glucose or in the presence of monolodoacetate; inhibition of glycolysis by glucosamine and NADH did not seem to affect the subcellular basis for protein synthesis. When present, the defect of the cell sap (monoiodoacetate and absence of glucose) and to disaggregation and reduced functional capacity of the polysomes (absence of glucose). The results suggested that the effects of the inhibition of glycolysis on protein synthesis and on the integrity of the protein-synthesizing machinery--which were primarily due to the depletion of the energy stores--might have been modified by the particular mechanism of action of the inhibitor and by the way low levels of ATP were reached in the cell.", "contents": "Inhibition of glycolysis and interference with protein synthesis in hepatoma cells. Ascites hepatoma cells grown in Wistar rats were incubated anaerobically in the absence of glucose or in the presence of both glucose and D(+)glucosamine, or monoiodoacetate, or NADH, which interfered with glycolysis at different steps and with different mechanisms: Under all these conditions the incorporation of amino acids into the proteins of hepatoma cells was severely reduced without any clear relationship to the degree of inhibition of glycolysis. The postmitochondrial supernatants showed defective incorporation only when obtained from cells incubated in the absence of glucose or in the presence of monolodoacetate; inhibition of glycolysis by glucosamine and NADH did not seem to affect the subcellular basis for protein synthesis. When present, the defect of the cell sap (monoiodoacetate and absence of glucose) and to disaggregation and reduced functional capacity of the polysomes (absence of glucose). The results suggested that the effects of the inhibition of glycolysis on protein synthesis and on the integrity of the protein-synthesizing machinery--which were primarily due to the depletion of the energy stores--might have been modified by the particular mechanism of action of the inhibitor and by the way low levels of ATP were reached in the cell."}
{"id": "PMID:190412", "title": "Immunosuppression in mice after inoculation with 334C, a murine lymphatic leukemia-inducing virus.", "content": "334C murine leukemia virus, which induces a high incidence of lymphatic leukemias (80-90%) in susceptible mice following a long latency period, was found to cause a severe in vivo suppression of direct plaque-forming cells from the spleen, following antigenic stimulation with sheep red blood cells. Neonatally infected inbred BALB/c and outbred Ha/ICR Swiss mice, which develop a sustained viremia, were highly susceptible to the immunosuppressive effect of this virus as early as 1 week after virus infection, long before any detectable histologic evidence of leukemia development. Ha/ICR Swiss mice, which are highly resistant to the leukemogenic potential of this virus following infection in adult life, were highly resistant to its immunosuppressive action; only a moderate and transient suppression, without viremia, occurred 2 weeks after virus infection. In marked contrast, BALB/c mice were highly susceptible to the immunosuppressive action of 334C murine leukemia virus following infection in adult life; a severe and sustained suppression was observed as early as 1 week after virus infection and was followed by a sustained viremia, beginning at 2 weeks, with a 55-60% incidence of leukemia observed over a period of 1 year. Infectious virus was essential to produce theimmunosuppressive effect; heat-inactivated (56 degrees C/30 min) and attenuated (4 degrees C/4 1/2 mo) virus preparations were ineffective. The plaque-forming response of spleen cells from lethally irradiated syngeneic adult BALB/c mice was markedly suppressed following reconstitution with thymus-dependent (T) or thymus-independent (B) cells from the thymus and bone marrow, respectively, of virus-infected mice, in combination with each other, or with the appropriate cell populations from normal mice.", "contents": "Immunosuppression in mice after inoculation with 334C, a murine lymphatic leukemia-inducing virus. 334C murine leukemia virus, which induces a high incidence of lymphatic leukemias (80-90%) in susceptible mice following a long latency period, was found to cause a severe in vivo suppression of direct plaque-forming cells from the spleen, following antigenic stimulation with sheep red blood cells. Neonatally infected inbred BALB/c and outbred Ha/ICR Swiss mice, which develop a sustained viremia, were highly susceptible to the immunosuppressive effect of this virus as early as 1 week after virus infection, long before any detectable histologic evidence of leukemia development. Ha/ICR Swiss mice, which are highly resistant to the leukemogenic potential of this virus following infection in adult life, were highly resistant to its immunosuppressive action; only a moderate and transient suppression, without viremia, occurred 2 weeks after virus infection. In marked contrast, BALB/c mice were highly susceptible to the immunosuppressive action of 334C murine leukemia virus following infection in adult life; a severe and sustained suppression was observed as early as 1 week after virus infection and was followed by a sustained viremia, beginning at 2 weeks, with a 55-60% incidence of leukemia observed over a period of 1 year. Infectious virus was essential to produce theimmunosuppressive effect; heat-inactivated (56 degrees C/30 min) and attenuated (4 degrees C/4 1/2 mo) virus preparations were ineffective. The plaque-forming response of spleen cells from lethally irradiated syngeneic adult BALB/c mice was markedly suppressed following reconstitution with thymus-dependent (T) or thymus-independent (B) cells from the thymus and bone marrow, respectively, of virus-infected mice, in combination with each other, or with the appropriate cell populations from normal mice."}
{"id": "PMID:190413", "title": "Reduced incidence of Marek's disease gross lymphomas in T-cell-depleted chickens.", "content": "Chickens of line 7, highly susceptible to Marek's disease (MD), were depleted of T-cells by neonatal thymectomy, total-body gamma-irradiation, and multiple injections with antithymocyte serum. In two replicate experiments, significantly fewer gross lymphomas were present in T-cell-depleted chickens than in intact or in T-cell-depleted, reconstituted hatchmates; these findings provided evidence that T-cells may be the principal target for MD virus (MDV) transformation, T-cell depletion was not complete, and the presence of microscopic lesions in T-cell-depleted chickens was attributed to residual T-cells. Ten lymphomas from intact chickens and 2 lymphomas from a T-cell-depleted chicken were examined for cellular composition. All lymphomas consisted predominantly of T-cells. The results of this and other published studies indicated that T-cells may have a dual role in MD; They may serve as a target for lymphoma formation by MDV and also may participate in immune surveillance against the disease in resistant chickens.", "contents": "Reduced incidence of Marek's disease gross lymphomas in T-cell-depleted chickens. Chickens of line 7, highly susceptible to Marek's disease (MD), were depleted of T-cells by neonatal thymectomy, total-body gamma-irradiation, and multiple injections with antithymocyte serum. In two replicate experiments, significantly fewer gross lymphomas were present in T-cell-depleted chickens than in intact or in T-cell-depleted, reconstituted hatchmates; these findings provided evidence that T-cells may be the principal target for MD virus (MDV) transformation, T-cell depletion was not complete, and the presence of microscopic lesions in T-cell-depleted chickens was attributed to residual T-cells. Ten lymphomas from intact chickens and 2 lymphomas from a T-cell-depleted chicken were examined for cellular composition. All lymphomas consisted predominantly of T-cells. The results of this and other published studies indicated that T-cells may have a dual role in MD; They may serve as a target for lymphoma formation by MDV and also may participate in immune surveillance against the disease in resistant chickens."}
{"id": "PMID:190414", "title": "Temperature-sensitive variants for saturation density and anchorage dependencey of a simian virus 40-transformed human X mouse hybrid cell line.", "content": "Several variant clones temperature sensitive for some parameters of transformation from a hybrid cell line containing a stable diploid mouse genome and two human chromosomes 7 carrying an integrated defective simian virus 40 have been isolated. Like the wild-type (wt) cells, at the permissive temperature the temperature-sensitive (ts) clones grew to high saturation densities and readily formed colonies in methyl cellulose. In contrast to the wt cells, at the nonpermissive temperature they had variable but always lower saturation densities and were unable to form colonies in methyl cellulose. The fraction of cells that synthesized DNA decreased at both temperatures when the cells reached saturation density, but it represented always at least 20% of the total population. All of the ts clones so far tested had a near triploid chromosome number, contained from one to three human chromosomes 7, and were T-antigen-positive both at the permissive and nonpermissive temperatures. The ts clones maintained low saturation density at the nonpermissive temperature because of a decrease in the number of cells that were actively proliferating and because of the shedding of cells into the medium. Temperature downshifts and refeeding allowed for expression of the permissive phenotype. In most of the isolated clones anchorage independency was not correlated with unrestricted cell proliferation. These variant clones may provide useful systems for a better understanding of the number of interdependent pathways involved in the expression of the phenotype of a transformed cell and elucidate the molecular mechanism required for the maintenance of a normal state in a cell population.", "contents": "Temperature-sensitive variants for saturation density and anchorage dependencey of a simian virus 40-transformed human X mouse hybrid cell line. Several variant clones temperature sensitive for some parameters of transformation from a hybrid cell line containing a stable diploid mouse genome and two human chromosomes 7 carrying an integrated defective simian virus 40 have been isolated. Like the wild-type (wt) cells, at the permissive temperature the temperature-sensitive (ts) clones grew to high saturation densities and readily formed colonies in methyl cellulose. In contrast to the wt cells, at the nonpermissive temperature they had variable but always lower saturation densities and were unable to form colonies in methyl cellulose. The fraction of cells that synthesized DNA decreased at both temperatures when the cells reached saturation density, but it represented always at least 20% of the total population. All of the ts clones so far tested had a near triploid chromosome number, contained from one to three human chromosomes 7, and were T-antigen-positive both at the permissive and nonpermissive temperatures. The ts clones maintained low saturation density at the nonpermissive temperature because of a decrease in the number of cells that were actively proliferating and because of the shedding of cells into the medium. Temperature downshifts and refeeding allowed for expression of the permissive phenotype. In most of the isolated clones anchorage independency was not correlated with unrestricted cell proliferation. These variant clones may provide useful systems for a better understanding of the number of interdependent pathways involved in the expression of the phenotype of a transformed cell and elucidate the molecular mechanism required for the maintenance of a normal state in a cell population."}
{"id": "PMID:190415", "title": "Isolation of polyoma virus-induced surface antigens in hamster cells: potassium chloride solubilization and differential precipitation.", "content": "Surface antigens were extracted in soluble and active form with 3 M KCL from polyoma virus-transformed and embryonic hamster cells. These were tumor-specific transplantation antigens (TSTA), shown by tumor rejection, and a surface (S) antigen, demonstrated by the inhibition of surface fluorescence on living polyoma virus-transformed cells. The extracts were fractionated by salting out with ammonium sulfate. In tumor cell extracts, all TSTA activity and a part of S antigen activity were found in the fraction precipitated with 60% saturation in (NH/)2SO4. Another part of S antigen activity was found in the fraction precipitating at 80% saturation in tumor cell extracts. The precipitate at 60% saturation of embryonic cell extracts also had a part of S antigen activity. Receptor site activity for concanavalin A was also retained after solubilization and was confined to the 40% saturation (NH4)2SO4 precipitate in the case of tumor and embryonic cell extracts.", "contents": "Isolation of polyoma virus-induced surface antigens in hamster cells: potassium chloride solubilization and differential precipitation. Surface antigens were extracted in soluble and active form with 3 M KCL from polyoma virus-transformed and embryonic hamster cells. These were tumor-specific transplantation antigens (TSTA), shown by tumor rejection, and a surface (S) antigen, demonstrated by the inhibition of surface fluorescence on living polyoma virus-transformed cells. The extracts were fractionated by salting out with ammonium sulfate. In tumor cell extracts, all TSTA activity and a part of S antigen activity were found in the fraction precipitated with 60% saturation in (NH/)2SO4. Another part of S antigen activity was found in the fraction precipitating at 80% saturation in tumor cell extracts. The precipitate at 60% saturation of embryonic cell extracts also had a part of S antigen activity. Receptor site activity for concanavalin A was also retained after solubilization and was confined to the 40% saturation (NH4)2SO4 precipitate in the case of tumor and embryonic cell extracts."}
{"id": "PMID:190416", "title": "Inhibition of mammary tumors by incomplete T-cell depletion.", "content": "The effects of neonatal and perinatal thymectomy on mammary tumorigenesis in (C57BL X I)F1fC3H hybrid female mice were determined. When hybrid females were neonatally thymectomized by controlled suction, a procedure that removes thymic lobes completely, a large proportion of animals developed stigmas of a fulminant wasting disease and died before tumors developed. However, when hybrid females were subjected to neonatal thymectomy by continuous suction, a procedure that resulted in retention of thymic remnants, they survived and manifested a significant prolongation of latent period before tumorigenesis. When complete removal of the thymus was carried out in the perinatal period, the effect on mammary tumorigenesis was critically dependent on the age at surgery. The procedure was without effect when performed at 1, 3, and 8 weeks of age. However, when it was performed at 9-12 days of age, there was a delay or a decrease in the appearance of mammary tumors. The extent of T-cell depletion and/or its timing in relationship to the introduction of murine mammary tumor virus appeared to play a critical role in determining the effect on eventual tumor development.", "contents": "Inhibition of mammary tumors by incomplete T-cell depletion. The effects of neonatal and perinatal thymectomy on mammary tumorigenesis in (C57BL X I)F1fC3H hybrid female mice were determined. When hybrid females were neonatally thymectomized by controlled suction, a procedure that removes thymic lobes completely, a large proportion of animals developed stigmas of a fulminant wasting disease and died before tumors developed. However, when hybrid females were subjected to neonatal thymectomy by continuous suction, a procedure that resulted in retention of thymic remnants, they survived and manifested a significant prolongation of latent period before tumorigenesis. When complete removal of the thymus was carried out in the perinatal period, the effect on mammary tumorigenesis was critically dependent on the age at surgery. The procedure was without effect when performed at 1, 3, and 8 weeks of age. However, when it was performed at 9-12 days of age, there was a delay or a decrease in the appearance of mammary tumors. The extent of T-cell depletion and/or its timing in relationship to the introduction of murine mammary tumor virus appeared to play a critical role in determining the effect on eventual tumor development."}
{"id": "PMID:190417", "title": "Antibodies to the R component of Epstein-Barr virus-induced early antigens in Burkitt's lymphoma exceeding in titer antibodies to Epstein-Barr capsid antigen.", "content": "African patients with Burkitt's lymphoma (BL) may show antibodies to the R (restricted) component of the Epstein-Barr (EB) virus-induced early antigens that appear to match in titer the antibodies to EB viral capsid antigen (VCA) as determined with the aid of acetone-fixed smears of EB3 cells. Virus-producing EB3 cells, however, contain the R component as well as VCA so that the correct anti-VCA titers in such cases remain in doubt. Since the R component, but not VCA, was found to be denatured by methanol fixation, the parallel use of acetone- and methanol-fixed EB3 cell smears permitted the determination of the correct anti-VCA titer. Our results showed that the anti-R titers of BL patients can in fact be up to eightfold higher than the anti-VCA titers. Anti-R titers equaling or exceeding anti-VCA titers have been encountered thus far only in BL.", "contents": "Antibodies to the R component of Epstein-Barr virus-induced early antigens in Burkitt's lymphoma exceeding in titer antibodies to Epstein-Barr capsid antigen. African patients with Burkitt's lymphoma (BL) may show antibodies to the R (restricted) component of the Epstein-Barr (EB) virus-induced early antigens that appear to match in titer the antibodies to EB viral capsid antigen (VCA) as determined with the aid of acetone-fixed smears of EB3 cells. Virus-producing EB3 cells, however, contain the R component as well as VCA so that the correct anti-VCA titers in such cases remain in doubt. Since the R component, but not VCA, was found to be denatured by methanol fixation, the parallel use of acetone- and methanol-fixed EB3 cell smears permitted the determination of the correct anti-VCA titer. Our results showed that the anti-R titers of BL patients can in fact be up to eightfold higher than the anti-VCA titers. Anti-R titers equaling or exceeding anti-VCA titers have been encountered thus far only in BL."}
{"id": "PMID:190418", "title": "Preparation of cell-free feline oncornavirus-associated cell membrane antigen.", "content": "Cell-free feline oncornavirus-associated cell membrane antigen (FOCMA) was prepared from a feline lymphoblastoid cell line of tumor origin (FL-74). Membrane fractions, separated on sucrose density gradients, and papain-solubilized products were found to contain FOCMA as determined by their capacity to inhibit reference cytotoxic cat antisera.", "contents": "Preparation of cell-free feline oncornavirus-associated cell membrane antigen. Cell-free feline oncornavirus-associated cell membrane antigen (FOCMA) was prepared from a feline lymphoblastoid cell line of tumor origin (FL-74). Membrane fractions, separated on sucrose density gradients, and papain-solubilized products were found to contain FOCMA as determined by their capacity to inhibit reference cytotoxic cat antisera."}
{"id": "PMID:190419", "title": "Intracytoplasmic type A particles in viper spleen cells.", "content": "Structures resembling typical type A particles were observed in paranuclear inclusions in cultured C-type particle-producing viper cells (VSW cell line). The incidence of type A particle inclusions was low (approximately 0.5% of cell profiles examined) in untreated cells, but both the incidence and size of the inclusions were slightly increased in cells treated with ethidium bromide. This is apparently the first observation of type A particles in cells of a poikilothermic vertebrate.", "contents": "Intracytoplasmic type A particles in viper spleen cells. Structures resembling typical type A particles were observed in paranuclear inclusions in cultured C-type particle-producing viper cells (VSW cell line). The incidence of type A particle inclusions was low (approximately 0.5% of cell profiles examined) in untreated cells, but both the incidence and size of the inclusions were slightly increased in cells treated with ethidium bromide. This is apparently the first observation of type A particles in cells of a poikilothermic vertebrate."}
{"id": "PMID:190420", "title": "Enhancement of R3230AC rat mammary tumor growth and cellular differentiation by dibutyryl cyclic adenosine monophosphate.", "content": "Daily sc injections of 8 mg N6, O2'-dibutyryl 3',5'-cyclic AMP (DBcAMP) beginning 1 day after tumor implantation significantly increased the growth rate of R32230AC rat mammary adenocarcinomas, which nearly doubled in in situ volume by day 40 compared to similarly implanted tumors in saline-injected controls. Weights of excised tumors, intact, drained, and dried all increased approximately 80%, which suggested that the increase in tumor size was not due to accumulation of secreted fluid or tissue water. Injections of 17beta-estradiol valerate (0.1 mg/wk) from day 1 or of DBcAMP from day 22 resulted in insignificant changes in growth--28% and 35% increases in tumor volume and a 5% decrease and an 18% increase, respectively, in drained wet weight. Electron microscopic examination revealed that estrogen and DBcAMP caused differentiation of the tumor cells into two different states: Estrogen-treated tumors resembled lactating mammary glands; they contained large lipid droplets, organized rough endoplasmic reticulum, and vesicles containing electron dense granules resembling protein. DBcAMP-treated tumor cells were marked by a proliferation of the Golgi complex and numerous vesicles containing fine granular material.", "contents": "Enhancement of R3230AC rat mammary tumor growth and cellular differentiation by dibutyryl cyclic adenosine monophosphate. Daily sc injections of 8 mg N6, O2'-dibutyryl 3',5'-cyclic AMP (DBcAMP) beginning 1 day after tumor implantation significantly increased the growth rate of R32230AC rat mammary adenocarcinomas, which nearly doubled in in situ volume by day 40 compared to similarly implanted tumors in saline-injected controls. Weights of excised tumors, intact, drained, and dried all increased approximately 80%, which suggested that the increase in tumor size was not due to accumulation of secreted fluid or tissue water. Injections of 17beta-estradiol valerate (0.1 mg/wk) from day 1 or of DBcAMP from day 22 resulted in insignificant changes in growth--28% and 35% increases in tumor volume and a 5% decrease and an 18% increase, respectively, in drained wet weight. Electron microscopic examination revealed that estrogen and DBcAMP caused differentiation of the tumor cells into two different states: Estrogen-treated tumors resembled lactating mammary glands; they contained large lipid droplets, organized rough endoplasmic reticulum, and vesicles containing electron dense granules resembling protein. DBcAMP-treated tumor cells were marked by a proliferation of the Golgi complex and numerous vesicles containing fine granular material."}
{"id": "PMID:190421", "title": "Culicoides, the vector of epizootic hemorrhagic disease in white-tailed deer in Kentucky in 1971.", "content": "The biting gnat, Culicoides variipennis (Coquillett), was shown to be a vector of epizootic hemorrhagic disease (EHD) in white-tailed deer, Odocoileus virginianus, in Kentucky because of virus isolations from parous females. Epidemiological evidence showed a close relationship of this vector to the animal host during an outbreak of EHD in penned deer. Larval breeding sites of C. variipennis were found and C. variipennis was the most abundant biting fly present during the outbreak. Females of C. variipennis were commonly observed biting deer, swine, cattle and, occasionally, man.", "contents": "Culicoides, the vector of epizootic hemorrhagic disease in white-tailed deer in Kentucky in 1971. The biting gnat, Culicoides variipennis (Coquillett), was shown to be a vector of epizootic hemorrhagic disease (EHD) in white-tailed deer, Odocoileus virginianus, in Kentucky because of virus isolations from parous females. Epidemiological evidence showed a close relationship of this vector to the animal host during an outbreak of EHD in penned deer. Larval breeding sites of C. variipennis were found and C. variipennis was the most abundant biting fly present during the outbreak. Females of C. variipennis were commonly observed biting deer, swine, cattle and, occasionally, man."}
{"id": "PMID:190422", "title": "Viruses isolated from captive and free-ranging wild ruminants in Alberta.", "content": "Nasal secretions, leukocytes and preputial or vaginal swabs from a group of 15 captive wild ruminants, comprising six pronghorn antelope (Antilocapra americana), seven fallow deer (Dama dama) and two mule deer (Odocoileus hemionus), and from 50 free-ranging pronghorns in southern Alberta, were examined for viral agents. Captive animals were given injections of dexamethasone daily for 6 days in attempts to reactivate latent infections. Specimens were collected at 2-3 day intervals from days 0 to 18. Free-ranging pronghorns were sampled only once, at the time of capture. Fifteen viral isolates were obtained from the animals: six isolates of parainfluenza 3 (PI3) from nasal swabs from one fallow deer and one mule deer; five isolates of herpesvirus from leukocytes, vaginal, preputial and nasal swabs from three fallow deer; and four isolates of PI3 from nasal secretions of the 50 free-ranging pronghorns.", "contents": "Viruses isolated from captive and free-ranging wild ruminants in Alberta. Nasal secretions, leukocytes and preputial or vaginal swabs from a group of 15 captive wild ruminants, comprising six pronghorn antelope (Antilocapra americana), seven fallow deer (Dama dama) and two mule deer (Odocoileus hemionus), and from 50 free-ranging pronghorns in southern Alberta, were examined for viral agents. Captive animals were given injections of dexamethasone daily for 6 days in attempts to reactivate latent infections. Specimens were collected at 2-3 day intervals from days 0 to 18. Free-ranging pronghorns were sampled only once, at the time of capture. Fifteen viral isolates were obtained from the animals: six isolates of parainfluenza 3 (PI3) from nasal swabs from one fallow deer and one mule deer; five isolates of herpesvirus from leukocytes, vaginal, preputial and nasal swabs from three fallow deer; and four isolates of PI3 from nasal secretions of the 50 free-ranging pronghorns."}
{"id": "PMID:190423", "title": "Herpesvirus sylvilagus in cottontail rabbits: evidence of shedding but not transplacental transmission.", "content": "Herpesvirus sylvilagus was inoculated into five cottontail rabbits (Sylvilagus floridanus) at various stages of pregnancy; they subsequently had litters in the laboratory. Three other cottontails chronically infected with the virus were bred and bore young in large outdoor pens. Thirty-four living neonates and dead fetuses were weighed, measured and aseptically necropsied. A total of 31 liver, spleen and kidney samples, 16 lymph node, 28 heart and 10 brain samples were collected and processed for inoculation into rabbit kidney cell cultures to attempt virus isolation. Virus was not detected in the 147 tissue samples tested. Pre-conception viremias ranged from 10-21 plaque-forming units per 0.5 ml. Virus isolation was attempted from 26 oral and lacrymal, 23 genital, nine urine and fecal, and four milk and male ejaculate samples from eight infected rabbits. Virus was recovered from two salivary samples from the same rabbit. Triamcinolone acetonide administered daily for four days to five rabbits did not stimulate excretion of virus.", "contents": "Herpesvirus sylvilagus in cottontail rabbits: evidence of shedding but not transplacental transmission. Herpesvirus sylvilagus was inoculated into five cottontail rabbits (Sylvilagus floridanus) at various stages of pregnancy; they subsequently had litters in the laboratory. Three other cottontails chronically infected with the virus were bred and bore young in large outdoor pens. Thirty-four living neonates and dead fetuses were weighed, measured and aseptically necropsied. A total of 31 liver, spleen and kidney samples, 16 lymph node, 28 heart and 10 brain samples were collected and processed for inoculation into rabbit kidney cell cultures to attempt virus isolation. Virus was not detected in the 147 tissue samples tested. Pre-conception viremias ranged from 10-21 plaque-forming units per 0.5 ml. Virus isolation was attempted from 26 oral and lacrymal, 23 genital, nine urine and fecal, and four milk and male ejaculate samples from eight infected rabbits. Virus was recovered from two salivary samples from the same rabbit. Triamcinolone acetonide administered daily for four days to five rabbits did not stimulate excretion of virus."}
{"id": "PMID:190424", "title": "Transmission of two strains of epizootic hemorrhagic disease virus in deer by Culicoides variipennis.", "content": "Two strains of epizootic hemorrhagic disease virus (EHDV), New Jersey (NJ) and Kentucky (KY), of deer were biologically transmitted between white-tailed deer, Odocoileus virginianus, by Culicoides variipennis. The KY strain, isolated from C. variipennis collected during an epizootic in deer, was identified as EHDV by serological tests. Deer exposed to the KY or the NJ strains of EHDV developed an acute hemorrhagic disease; most deer died 6 to 13 days after infection. Sheep inoculated with EHDV developed no clinical signs of disease.", "contents": "Transmission of two strains of epizootic hemorrhagic disease virus in deer by Culicoides variipennis. Two strains of epizootic hemorrhagic disease virus (EHDV), New Jersey (NJ) and Kentucky (KY), of deer were biologically transmitted between white-tailed deer, Odocoileus virginianus, by Culicoides variipennis. The KY strain, isolated from C. variipennis collected during an epizootic in deer, was identified as EHDV by serological tests. Deer exposed to the KY or the NJ strains of EHDV developed an acute hemorrhagic disease; most deer died 6 to 13 days after infection. Sheep inoculated with EHDV developed no clinical signs of disease."}
{"id": "PMID:190425", "title": "Herpesvirus sylvilagus in cottontail rabbits: attempted laboratory transmission by two insect species.", "content": "The vector potential of the rabbit flea (Cediopsylla simplex) and a mosquito (Aedes triseriatus) was investigated for Herpesvirus sylvilagus transmission among cottontail rabbits (Sylvilagus floridanus). Twelve groups of 12-50 fleas were fed on three viremic cottontails for 2-21 days before transfer to 12 susceptible rabbits. Standard interrupted feeding trials employed five groups of 6-12 mosquitoes, two viremic donor cottontails anf five healthy recipients. No evidence of virus was detected from recipients' blood nor did they develop specific antibody. Virus acquisition and persistence in the insects was evaluated by attempting to recover the virus from 19 pools of mosquitoes engorged on viremic blood and 36 pools of engorged fleas or those living on viremic hosts for 1-21 days. Results were negative.", "contents": "Herpesvirus sylvilagus in cottontail rabbits: attempted laboratory transmission by two insect species. The vector potential of the rabbit flea (Cediopsylla simplex) and a mosquito (Aedes triseriatus) was investigated for Herpesvirus sylvilagus transmission among cottontail rabbits (Sylvilagus floridanus). Twelve groups of 12-50 fleas were fed on three viremic cottontails for 2-21 days before transfer to 12 susceptible rabbits. Standard interrupted feeding trials employed five groups of 6-12 mosquitoes, two viremic donor cottontails anf five healthy recipients. No evidence of virus was detected from recipients' blood nor did they develop specific antibody. Virus acquisition and persistence in the insects was evaluated by attempting to recover the virus from 19 pools of mosquitoes engorged on viremic blood and 36 pools of engorged fleas or those living on viremic hosts for 1-21 days. Results were negative."}
{"id": "PMID:190426", "title": "Dietary treatment of type IV hyperlipoproteinemia.", "content": "This communication describes an investigation of the effectiveness of dietary counseling in the treatment of patients classified phenotypically as having type IV hyperlipoproteinemia or endogenous hypertriglyceridemia. Over a period of two years, 103 patients who received instructions for a therapeutic diet and regular dietary counseling by a physician and dietitian had a large decline in the concentration of serum triglycerides, as compared to 175 patients with the same diagnosis who received similar diets but little dietary counseling. Over the period of the study, the median plasma triglyceride concentration decreased from 302 to 210 mg/100 ml, the mean triglyceride value from 381 to 263 mg/100 ml, and the mean weight from 84 to 80 kg in the group receiving dietary counseling.", "contents": "Dietary treatment of type IV hyperlipoproteinemia. This communication describes an investigation of the effectiveness of dietary counseling in the treatment of patients classified phenotypically as having type IV hyperlipoproteinemia or endogenous hypertriglyceridemia. Over a period of two years, 103 patients who received instructions for a therapeutic diet and regular dietary counseling by a physician and dietitian had a large decline in the concentration of serum triglycerides, as compared to 175 patients with the same diagnosis who received similar diets but little dietary counseling. Over the period of the study, the median plasma triglyceride concentration decreased from 302 to 210 mg/100 ml, the mean triglyceride value from 381 to 263 mg/100 ml, and the mean weight from 84 to 80 kg in the group receiving dietary counseling."}
{"id": "PMID:190427", "title": "Combination chemotherapy and radiation therapy for small cell carcinoma.", "content": "A three-drug combination of the chemotherapeutic agents cyclophosphamide, vincristine sulfate, and doxorubicin hydrochloride was given to 45 patients with small cell bronchogenic carcinoma. In addition, patients with limited disease received radiation therapy to the primary tumor. The complete response rate was 44%, with a median survival of 50 weeks. The partial response rate was 29%, with a median survival of 35 weeks. Patients who did not respond to therapy showed a median survival of only 12 weeks. Twenty percent of the patients had their first recurrence in the brain, and the median survival from the time of disease recurrence was ten weeks. Bone marrow metastasis was encountered in 24% of the patient population, but this did not adversely affect survival.", "contents": "Combination chemotherapy and radiation therapy for small cell carcinoma. A three-drug combination of the chemotherapeutic agents cyclophosphamide, vincristine sulfate, and doxorubicin hydrochloride was given to 45 patients with small cell bronchogenic carcinoma. In addition, patients with limited disease received radiation therapy to the primary tumor. The complete response rate was 44%, with a median survival of 50 weeks. The partial response rate was 29%, with a median survival of 35 weeks. Patients who did not respond to therapy showed a median survival of only 12 weeks. Twenty percent of the patients had their first recurrence in the brain, and the median survival from the time of disease recurrence was ten weeks. Bone marrow metastasis was encountered in 24% of the patient population, but this did not adversely affect survival."}
{"id": "PMID:190431", "title": "Serological relationships among some Pichia species.", "content": "Antigenic analyses of five species of the genus Pichia were carried out for taxonomic study by the slide agglutination method using monospecific and absorbed antisera and the agglutinin absorption technique. Comparative studies were also performed with a few strains of each of the same species and their classifications are discussed with respect to the antigenic structures and the patterns of proton magnetic resonance (PMR) spectra of their cell wall polysaccharides. ichia delftensis and Pichia zaruensis possessed thermostable antigens 1,2,5 and 11, and the former had also thermoabile antigen m. Both species were closely related to Candida krusei. Pichia toletana possessed thermostable antigens 1,2,5,11,17 and 49. Pichia bovis contained thermostable antigens 1,2,14,15,16,20 and 21, and it was related to most species of the genus Hansenula, although assimilation of potassium nitrate was negative. Finally, Pichia etchellsii possessed thermostable antigens 1,2,3,4,9 and 14, and was closely related to Pichia vini. Patterns of PMR spectra of mannans of these species also supported their serological relationships. Therfore, P. delftensis, P. zaruensis and P. etchellsii are considered to be the synonyms of Pichia fluxuum, Pichia dispora and P. vini respectively, although P. toletanan and P. bovis are independent species.", "contents": "Serological relationships among some Pichia species. Antigenic analyses of five species of the genus Pichia were carried out for taxonomic study by the slide agglutination method using monospecific and absorbed antisera and the agglutinin absorption technique. Comparative studies were also performed with a few strains of each of the same species and their classifications are discussed with respect to the antigenic structures and the patterns of proton magnetic resonance (PMR) spectra of their cell wall polysaccharides. ichia delftensis and Pichia zaruensis possessed thermostable antigens 1,2,5 and 11, and the former had also thermoabile antigen m. Both species were closely related to Candida krusei. Pichia toletana possessed thermostable antigens 1,2,5,11,17 and 49. Pichia bovis contained thermostable antigens 1,2,14,15,16,20 and 21, and it was related to most species of the genus Hansenula, although assimilation of potassium nitrate was negative. Finally, Pichia etchellsii possessed thermostable antigens 1,2,3,4,9 and 14, and was closely related to Pichia vini. Patterns of PMR spectra of mannans of these species also supported their serological relationships. Therfore, P. delftensis, P. zaruensis and P. etchellsii are considered to be the synonyms of Pichia fluxuum, Pichia dispora and P. vini respectively, although P. toletanan and P. bovis are independent species."}
{"id": "PMID:190432", "title": "Modulation of mouse anti-trinitrophenyl plaque-forming cell affinity by adjuvants or lectins.", "content": "The efffects of several kinds of adjuvants or lectins, such as Corynebacterium parvum, dextran, poly AU, poly IC, dibutyryl cAMP, concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) on anti-trinitrophenyl (TNP) direct plaque-forming cells (PFC) in the spleen of mice and the affinity of antibodies produced by these PFC were examined. The numbers of anti-TNP PFC in the spleens of mice which had been injected with C. parvum 7 days in advance were greater than those in controls after immunization with TNP-coupled heterologous erythrocytes, while the affinity of antibodies released by these PFC. Copolymers of nucleotides, poly AU and poly IC, were capable of enhancing splenic anti-TNP PFC responses, but showed almost no altering of PFC affinity. Dibutyryl cAMP did not have any effect on this system. Con A had potencies to both augment the number of anti-TNP PFC and heighten the PFC affinity, while PHA seemed to lack these potencies. Injection of PWM in the presence of antigen increased the number of anti-TNP PFC and heightened slightly the PFC affinity. These results indicate that the heightening of the affinity at the cellular level is regulated in ways different from the augmenting effects on the number of anti-TNP PFC by adjuvants or lectins. These results are discussed in the light of the mode of action of the substances used.", "contents": "Modulation of mouse anti-trinitrophenyl plaque-forming cell affinity by adjuvants or lectins. The efffects of several kinds of adjuvants or lectins, such as Corynebacterium parvum, dextran, poly AU, poly IC, dibutyryl cAMP, concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) on anti-trinitrophenyl (TNP) direct plaque-forming cells (PFC) in the spleen of mice and the affinity of antibodies produced by these PFC were examined. The numbers of anti-TNP PFC in the spleens of mice which had been injected with C. parvum 7 days in advance were greater than those in controls after immunization with TNP-coupled heterologous erythrocytes, while the affinity of antibodies released by these PFC. Copolymers of nucleotides, poly AU and poly IC, were capable of enhancing splenic anti-TNP PFC responses, but showed almost no altering of PFC affinity. Dibutyryl cAMP did not have any effect on this system. Con A had potencies to both augment the number of anti-TNP PFC and heighten the PFC affinity, while PHA seemed to lack these potencies. Injection of PWM in the presence of antigen increased the number of anti-TNP PFC and heightened slightly the PFC affinity. These results indicate that the heightening of the affinity at the cellular level is regulated in ways different from the augmenting effects on the number of anti-TNP PFC by adjuvants or lectins. These results are discussed in the light of the mode of action of the substances used."}
{"id": "PMID:190435", "title": "Effect of intestinal distention on levels of cyclic AMP and fluid secretion.", "content": "The effect of distention on levels of intestinal cyclic AMP has been examined in rabbit jejunal loops under conditions of distention causing fluid secretion. Cyclic AMP levels were not significantly changed when compared with control loops. Histologic examination of the distended loops showed no significant changes from normal. The data indicate that the secretion in response to distention can occur in absence of morphological alteration and is not mediated by the cyclic AMP system.", "contents": "Effect of intestinal distention on levels of cyclic AMP and fluid secretion. The effect of distention on levels of intestinal cyclic AMP has been examined in rabbit jejunal loops under conditions of distention causing fluid secretion. Cyclic AMP levels were not significantly changed when compared with control loops. Histologic examination of the distended loops showed no significant changes from normal. The data indicate that the secretion in response to distention can occur in absence of morphological alteration and is not mediated by the cyclic AMP system."}
{"id": "PMID:190436", "title": "Reduction of plasma triglycerides by diet in subjects with chronic renal failure.", "content": "The response of plasma triglyceride levels to changes in the composition of meal formula diets was studied in 12 subjects who had moderate to severe chronic renal failure. Fasting hypertriglyceridemia (greater than 150 mg/100 ml) was present in seven of 12 subjects. Fasting plasma triglyceride levels decreased in all subjects in response to a reduction in the proportion of carbohydrate (from 50 to 35% of total daily calories) and an increase in the poly-unsaturated to saturated fat ratio (from 0.2 to 2.0) in an isocaloric diet. Fasting plasma cholesterol and postprandial triglyceride levels were unchanged. Both the triglyceride production rate and the insulin response were significantly lower on a diet in carbohydrate and higher in polyunsaturated fat. These data indicate that hypertriglyceridemia occurs in subjects with moderate to severe chronic renal failure, and that dietary modification promptly reduces triglycerides levels over an 11 day period. A long term study on a dietary program incorporating these changes is indicated to determine whether this effect is sustained.", "contents": "Reduction of plasma triglycerides by diet in subjects with chronic renal failure. The response of plasma triglyceride levels to changes in the composition of meal formula diets was studied in 12 subjects who had moderate to severe chronic renal failure. Fasting hypertriglyceridemia (greater than 150 mg/100 ml) was present in seven of 12 subjects. Fasting plasma triglyceride levels decreased in all subjects in response to a reduction in the proportion of carbohydrate (from 50 to 35% of total daily calories) and an increase in the poly-unsaturated to saturated fat ratio (from 0.2 to 2.0) in an isocaloric diet. Fasting plasma cholesterol and postprandial triglyceride levels were unchanged. Both the triglyceride production rate and the insulin response were significantly lower on a diet in carbohydrate and higher in polyunsaturated fat. These data indicate that hypertriglyceridemia occurs in subjects with moderate to severe chronic renal failure, and that dietary modification promptly reduces triglycerides levels over an 11 day period. A long term study on a dietary program incorporating these changes is indicated to determine whether this effect is sustained."}
{"id": "PMID:190437", "title": "[Metaherpetic keratitis clinical and virological findings (author's transl)].", "content": "2,277 specimens from 901 eyes were cultured for herpes simplex virus (HSV). 161 of 391 herpes-diseased eyes yielded HSV. The clinico-virological correlation led to a simple diagnostic and therapeutic scheme which is applicable by the ophthalmologist in his office without virological confirmation: 1. Superficial viral herpes (dendritic keratitis and allied disorders), HSV-isolating rate 96%. 2. Stromal herpes (disciform edema, different types of interstitial herpetic keratitis), only sporadical findings of HSV in the lacrimal fluid. The rate of virus-recovery increases, however, when an interstitial herpetic keratitis ulcerates. 3. Metaherpetic corneal disease = chronic or chronic recurrent superficial postherpetic disease without any detectable HSV-activity (main types: metaherpetic erosion, metaherpetic ulcer, metaherpetic bullous keratopathy). One of four superficial herpetic corneal diseases proved to be nonviral, i.e. metaherpetic in our series. Metaherpetic diseases may be widely considered as a therapeutic entity. The differential diagnosis with the slitlamp only and the proposed therapy (highly hydrophilic soft lenses plus adequate additional eye drops) are discussed in detail. Being aware of the diagnostic criteria and taking advantage of a combined soft lens therapy the treatment of metaherpetic corneal disease is easier and more successful than commonly accepted.", "contents": "[Metaherpetic keratitis clinical and virological findings (author's transl)]. 2,277 specimens from 901 eyes were cultured for herpes simplex virus (HSV). 161 of 391 herpes-diseased eyes yielded HSV. The clinico-virological correlation led to a simple diagnostic and therapeutic scheme which is applicable by the ophthalmologist in his office without virological confirmation: 1. Superficial viral herpes (dendritic keratitis and allied disorders), HSV-isolating rate 96%. 2. Stromal herpes (disciform edema, different types of interstitial herpetic keratitis), only sporadical findings of HSV in the lacrimal fluid. The rate of virus-recovery increases, however, when an interstitial herpetic keratitis ulcerates. 3. Metaherpetic corneal disease = chronic or chronic recurrent superficial postherpetic disease without any detectable HSV-activity (main types: metaherpetic erosion, metaherpetic ulcer, metaherpetic bullous keratopathy). One of four superficial herpetic corneal diseases proved to be nonviral, i.e. metaherpetic in our series. Metaherpetic diseases may be widely considered as a therapeutic entity. The differential diagnosis with the slitlamp only and the proposed therapy (highly hydrophilic soft lenses plus adequate additional eye drops) are discussed in detail. Being aware of the diagnostic criteria and taking advantage of a combined soft lens therapy the treatment of metaherpetic corneal disease is easier and more successful than commonly accepted."}
{"id": "PMID:190438", "title": "[Diurnal patterns of plasma lipids and lipoproteins in primary endogenous hypertriglyceridemia (type IV-hyperlipoproteinemia) (author's transl)].", "content": "Acute and chronic effects of three isocaloric diets on plasma lipids and plasma lipoproteins were studied in 10 patients with primary endogenous hypertriglyceridemia (type IV-hyperlipoproteinemia). The diets used contained 20% protein, 50, 37 and 1% fat and 30, 43 and 79% carbohydrates respectively. Cholesterol levels were similar with all diets. Fasting values of plasma triglycerides were lower with the fat-containing diets compared to the high-carbohydrate diet. Diurnal patterns, however, were significantly higher with the former diets in 8 of the 10 patients.  Postprandial lipoprotein patterns on fat-containing diets are characterized by chylomicronemia and marked changes of concentration and composition of other lipoprotein classes. If, analogous to diabetic therapy, control of hypertriglyceridemia is meant to imply low all-day levels rather than low fasting levels, a rather low-fat, high-carbohydrate diet seems to be superior in most patients with endogenous hypertriglyceridemia to diets containing more than 35 calorie per cent of fat.", "contents": "[Diurnal patterns of plasma lipids and lipoproteins in primary endogenous hypertriglyceridemia (type IV-hyperlipoproteinemia) (author's transl)]. Acute and chronic effects of three isocaloric diets on plasma lipids and plasma lipoproteins were studied in 10 patients with primary endogenous hypertriglyceridemia (type IV-hyperlipoproteinemia). The diets used contained 20% protein, 50, 37 and 1% fat and 30, 43 and 79% carbohydrates respectively. Cholesterol levels were similar with all diets. Fasting values of plasma triglycerides were lower with the fat-containing diets compared to the high-carbohydrate diet. Diurnal patterns, however, were significantly higher with the former diets in 8 of the 10 patients.  Postprandial lipoprotein patterns on fat-containing diets are characterized by chylomicronemia and marked changes of concentration and composition of other lipoprotein classes. If, analogous to diabetic therapy, control of hypertriglyceridemia is meant to imply low all-day levels rather than low fasting levels, a rather low-fat, high-carbohydrate diet seems to be superior in most patients with endogenous hypertriglyceridemia to diets containing more than 35 calorie per cent of fat."}
{"id": "PMID:190466", "title": "The use of a simple barrier system to exclude murine pathogens.", "content": "A simple barrier system was used successfully to exclude Mycoplasma pulmonis and Sendai virus from a conventional mouse room. 49 weeks after introduction of the barrier system of management Pasteurella pneumotropica was first isolated from animals in the room.", "contents": "The use of a simple barrier system to exclude murine pathogens. A simple barrier system was used successfully to exclude Mycoplasma pulmonis and Sendai virus from a conventional mouse room. 49 weeks after introduction of the barrier system of management Pasteurella pneumotropica was first isolated from animals in the room."}
{"id": "PMID:190468", "title": "Sertoli-Leydig cell tumor in a chimpanzee.", "content": "Microscopic analysis of a 38-year-old chimpanzee (Pan troglodytes) revealed a well differentiated Sertoli-Leydig cell tumor (arrhenoblastoma), 4 mm in diameter. Extensive follicular atresia and thecal hypertrophy were noted. The endometrium showed extensive adenomatous hyperplasia, an indication of hyperestrinism. It was suggested that the apparent excessive estrogenic secretion might have originated in the hypertrophic thecal tissue rather than in the tumor.", "contents": "Sertoli-Leydig cell tumor in a chimpanzee. Microscopic analysis of a 38-year-old chimpanzee (Pan troglodytes) revealed a well differentiated Sertoli-Leydig cell tumor (arrhenoblastoma), 4 mm in diameter. Extensive follicular atresia and thecal hypertrophy were noted. The endometrium showed extensive adenomatous hyperplasia, an indication of hyperestrinism. It was suggested that the apparent excessive estrogenic secretion might have originated in the hypertrophic thecal tissue rather than in the tumor."}
{"id": "PMID:190470", "title": "Microbial agents of the owl monkey (Aotus trivirgatus).", "content": "A survey of the microbial flora in the owl monkey (Aotus trivirgatus) has led to the isolation of numerous bacterial, fungal, and viral agents. Some of the bacterial and fungal agents, particularly Dermatophilus, Pasteurella, Salmonella, Shigella, Yersinia, Streptococcus, Staphylococcus, and Candida are known pathogens. Viruses belonging to the herpesvirus, adenovirus, paramyxovirus, and papovavirus groups have been isolated from the owl monkey. Most of these viruses were recovered as latent agents from kidney cell cultures. Thus far, they have not been associated with clinical illness or specific lesions in the owl monkey and their infectivity for other animal hosts and for man is unknown.", "contents": "Microbial agents of the owl monkey (Aotus trivirgatus). A survey of the microbial flora in the owl monkey (Aotus trivirgatus) has led to the isolation of numerous bacterial, fungal, and viral agents. Some of the bacterial and fungal agents, particularly Dermatophilus, Pasteurella, Salmonella, Shigella, Yersinia, Streptococcus, Staphylococcus, and Candida are known pathogens. Viruses belonging to the herpesvirus, adenovirus, paramyxovirus, and papovavirus groups have been isolated from the owl monkey. Most of these viruses were recovered as latent agents from kidney cell cultures. Thus far, they have not been associated with clinical illness or specific lesions in the owl monkey and their infectivity for other animal hosts and for man is unknown."}
{"id": "PMID:190471", "title": "Glomerulonephritis in the owl monkey (Aotus trivirgatus): ultrastructural observations.", "content": "The kidneys of 11 clinically healthy owl monkeys (Aotus trivirgatus) acquired from four different sources were examined by light and electron microscopy. Eight of the 11 animals had morphologic evidence of glomerulonephritis. The lesions were characterized by one or more of the following changes: focal or segmental thickening of the glomerular basement membrane; proliferation of mesangial cells with increased production of mesangial matrix; and fibrosis and hyalinization of glomeruli with and without inflammatory cellular infiltration. Five of the eight animals with one or more of the above described changes had electron-dense deposits compatible with immune complex deposits in the intra-membranous and subepithelial regions of the basement membrane. The nature and source of the antigen or antigens responsible for the lesions are unknown.", "contents": "Glomerulonephritis in the owl monkey (Aotus trivirgatus): ultrastructural observations. The kidneys of 11 clinically healthy owl monkeys (Aotus trivirgatus) acquired from four different sources were examined by light and electron microscopy. Eight of the 11 animals had morphologic evidence of glomerulonephritis. The lesions were characterized by one or more of the following changes: focal or segmental thickening of the glomerular basement membrane; proliferation of mesangial cells with increased production of mesangial matrix; and fibrosis and hyalinization of glomeruli with and without inflammatory cellular infiltration. Five of the eight animals with one or more of the above described changes had electron-dense deposits compatible with immune complex deposits in the intra-membranous and subepithelial regions of the basement membrane. The nature and source of the antigen or antigens responsible for the lesions are unknown."}
{"id": "PMID:190472", "title": "The owl monkey (Aotus trivirgatus) as an animal model for viral diseases and oncologic studies.", "content": "The owl monkey (Aotus trivirgatus) has been shown to be an excellent model for studies of oncogenic and non-oncogenic viruses. Studies at this institution have been primarily concerned with Herpesvirus saimiri, the Epstein-Barr virus, H tamarinus, and H simplex. These studies have shown that H saimiri is oncogenic when inoculated into primates, that the malignancy induced by H saimiri can be naturally transmitted from the squirrel monkey to the owl monkey, that in vitro pathogenicity of H saimiri can be modified by passing the virus in a nonpermissive cellular host, that the owl monkey is a useful model for studying the oncogenicity of the Epstein-Barr virus, and the fatal disease induced in owl monkeys by H tamarinus and H simplex can be prevented by vaccination with nonpathogenic variants of these viruses.", "contents": "The owl monkey (Aotus trivirgatus) as an animal model for viral diseases and oncologic studies. The owl monkey (Aotus trivirgatus) has been shown to be an excellent model for studies of oncogenic and non-oncogenic viruses. Studies at this institution have been primarily concerned with Herpesvirus saimiri, the Epstein-Barr virus, H tamarinus, and H simplex. These studies have shown that H saimiri is oncogenic when inoculated into primates, that the malignancy induced by H saimiri can be naturally transmitted from the squirrel monkey to the owl monkey, that in vitro pathogenicity of H saimiri can be modified by passing the virus in a nonpermissive cellular host, that the owl monkey is a useful model for studying the oncogenicity of the Epstein-Barr virus, and the fatal disease induced in owl monkeys by H tamarinus and H simplex can be prevented by vaccination with nonpathogenic variants of these viruses."}
{"id": "PMID:190473", "title": "Studies of cultured lymphocytes of the owl monkey (Aotus trivirgatus) infected with Herpesvirus saimiri.", "content": "The lymphocytes of five owl monkeys (Aotus trivirgatus) infected with Herpesvirus saimiri and three control monkeys were studied. Lymphocytes were separated on Ficoll-Hypaque gradients, incubated in suspension cultures, and prepared for electron microscopic and immunofluorescent study at 24, 48, and 72 hours after the beginning of culture. Buffy coats of whole blood obtained immediately after bleeding were also prepared for study. At the time of the study, four of the five infected monkeys had died with malignant lymphoma and lymphocytic leukemia. Herpesvirus saimiri virions were demonstrated by electron microscopy and H saimiri antigens by immunofluorescence in 1-20% of the lymphocytes from infected monkey in two of five cultures at 24 hours after culture, four of five at 48 hours after culture, and all of five at 72 hours after culture. There was good agreement between the electron microscopic and the immunofluorescent data. None of the control monkey cultures and none of the buffy coat preparations contained H saimiri virions or antigens. By electron microscopy, the great majority of the virus particles were nucleocapsids within the nuclei of lymphocytes. Enveloped virions were seldom observed. There was some evidence to suggest that the higher the percentage of lymphocyte containing H saimiri, the poorer the prognosis for the monkey. Herpesvirus saimiri was isolated from all five infected monkeys by co-cultivation of lymphocytes with Vero cells. Control lymphocyte co-cultivations were negative.", "contents": "Studies of cultured lymphocytes of the owl monkey (Aotus trivirgatus) infected with Herpesvirus saimiri. The lymphocytes of five owl monkeys (Aotus trivirgatus) infected with Herpesvirus saimiri and three control monkeys were studied. Lymphocytes were separated on Ficoll-Hypaque gradients, incubated in suspension cultures, and prepared for electron microscopic and immunofluorescent study at 24, 48, and 72 hours after the beginning of culture. Buffy coats of whole blood obtained immediately after bleeding were also prepared for study. At the time of the study, four of the five infected monkeys had died with malignant lymphoma and lymphocytic leukemia. Herpesvirus saimiri virions were demonstrated by electron microscopy and H saimiri antigens by immunofluorescence in 1-20% of the lymphocytes from infected monkey in two of five cultures at 24 hours after culture, four of five at 48 hours after culture, and all of five at 72 hours after culture. There was good agreement between the electron microscopic and the immunofluorescent data. None of the control monkey cultures and none of the buffy coat preparations contained H saimiri virions or antigens. By electron microscopy, the great majority of the virus particles were nucleocapsids within the nuclei of lymphocytes. Enveloped virions were seldom observed. There was some evidence to suggest that the higher the percentage of lymphocyte containing H saimiri, the poorer the prognosis for the monkey. Herpesvirus saimiri was isolated from all five infected monkeys by co-cultivation of lymphocytes with Vero cells. Control lymphocyte co-cultivations were negative."}
{"id": "PMID:190474", "title": "EB virus in the owl monkey (Aotus trivirgatus).", "content": "Owl monkeys (Aotus trivirgatus) were inoculated with EB (Epstein-Barr) virus-containing material or virion-free control material. One out of three animals given the virus died after 14 weeks with a reticuloproliferative disease compatible with malignant lymphoma. A cell line was established from an abnormal lymph node of the diseased monkey and was found by electronmicroscopy to carry a herpesvirus identified as EB virus by two types of immunofluorescence test, by its biological behavior and by nucleic acid hybridization studies. None of the inoculated animals developed heterophile antibodies, and only the diseased animal had an antibody response to EB virus. The findings were discussed in relation to a possible oncogenic capacity of EB virus in vivo.", "contents": "EB virus in the owl monkey (Aotus trivirgatus). Owl monkeys (Aotus trivirgatus) were inoculated with EB (Epstein-Barr) virus-containing material or virion-free control material. One out of three animals given the virus died after 14 weeks with a reticuloproliferative disease compatible with malignant lymphoma. A cell line was established from an abnormal lymph node of the diseased monkey and was found by electronmicroscopy to carry a herpesvirus identified as EB virus by two types of immunofluorescence test, by its biological behavior and by nucleic acid hybridization studies. None of the inoculated animals developed heterophile antibodies, and only the diseased animal had an antibody response to EB virus. The findings were discussed in relation to a possible oncogenic capacity of EB virus in vivo."}
{"id": "PMID:190475", "title": "The transplacental toxicity of methyl mercury to fetal rat liver mitochondria. Morphometric and biochemical studies.", "content": "Ultrastructural morphometric and biochemical changes in liver mitochondria of fetal rats whose mothers were exposed to methyl mercury hydroxide in their drinking water at concentrations of 0, 3, 5, or 10 p.p.m. for 4 weeks prior to mating and through day 19 of pregnancy are described. A dose-related decrease in the volume density of mitochondria was observed in fetal hepatocytes of dams given the 5- and 10-p.p.m. dose levels. This finding was associated with decreased mitochondrial protein synthesis, which appeared to result primarily from decreased synthesis of mitochondrial structural proteins. Loss of respiratory control was observed in mitochondria from animals in the 3-p.p.m. dose group whereas state 3 respiration was abolished in animals exposed to the 5- and 10-p.p.m. dose levels. The specific activities of monoamine oxidase and cytochrome oxidase, outer and inner mitochondrial membrane marker enzymes respectively, showed dose-related decreases of up to 62 and 78 per cent of control, respectively. delta-Aminolevulinic acid synthetase, which is loosely bound to the inner mitochondrial membrane, also showed dose-related decreases of up to 68 per cent of control. Malate dehydrogenase, a mitochondrial matrix marker enzyme, showed no change in activity at any dose level tested. These observations were correlated with dose-related tissue concentrations of methyl and inormpaired mitochondrial biogenesis and functional development is one basis for explaining the sensitivity of fetal animals to methyl mercury toxicity.", "contents": "The transplacental toxicity of methyl mercury to fetal rat liver mitochondria. Morphometric and biochemical studies. Ultrastructural morphometric and biochemical changes in liver mitochondria of fetal rats whose mothers were exposed to methyl mercury hydroxide in their drinking water at concentrations of 0, 3, 5, or 10 p.p.m. for 4 weeks prior to mating and through day 19 of pregnancy are described. A dose-related decrease in the volume density of mitochondria was observed in fetal hepatocytes of dams given the 5- and 10-p.p.m. dose levels. This finding was associated with decreased mitochondrial protein synthesis, which appeared to result primarily from decreased synthesis of mitochondrial structural proteins. Loss of respiratory control was observed in mitochondria from animals in the 3-p.p.m. dose group whereas state 3 respiration was abolished in animals exposed to the 5- and 10-p.p.m. dose levels. The specific activities of monoamine oxidase and cytochrome oxidase, outer and inner mitochondrial membrane marker enzymes respectively, showed dose-related decreases of up to 62 and 78 per cent of control, respectively. delta-Aminolevulinic acid synthetase, which is loosely bound to the inner mitochondrial membrane, also showed dose-related decreases of up to 68 per cent of control. Malate dehydrogenase, a mitochondrial matrix marker enzyme, showed no change in activity at any dose level tested. These observations were correlated with dose-related tissue concentrations of methyl and inormpaired mitochondrial biogenesis and functional development is one basis for explaining the sensitivity of fetal animals to methyl mercury toxicity."}
{"id": "PMID:190476", "title": "The peroxisomes of human hepatocytes.", "content": "In an ultrastructural study of human liver biopsy specimens we found that peroxisomes are regularly present in normal human hepatocytes. Their relationships with the endoplasmic reticulum observed in other species and in other organs were also demonstrable in this material. Some normal peroxisomes were found to display marginal plates or peripheral crystalline inclusions which were present in pathologic specimens as well. In certain inherited metabolic disorders (Menkes' steely hair disease, analbuminemia) the volume of the individual peroxisomes appeared to be considerably reduced. But most pathologic processes affecting hepatocytes seem to produce any or several of the following: increased volume or numbers per cell, changes of shapes, alterations of the consistency of the matrix, appearance of dense numbers per cell, changes of shapes, alterations of the consistency of the matrix, appearance of dense inclusions, or clustering of peroxisomes in some portions of the cytoplasm. Some of these abnormalities are reversible based on observations in three patients with Wilson's disease treated with D-penicillamine. The mean +/- standard deviation of diameters of peroxisomes in four normal subjects was 0.618 +/- 0.143 mum. Significant reductions or increases in mean diameters of peroxisomes were noted in all but two of the 16 pathologic specimens. There were other morphologic abnormalities present in the remaining two specimens. We conclude that various pathologic processes involving the hepatocytic cytoplasm exert different effects on peroxisomes. Although no specific pattern of morphologic alteration emerged from this exploratory study, a possible involvement of peroxisomes ought to be considered whenever metabolic or pathologic processes affect the liver.", "contents": "The peroxisomes of human hepatocytes. In an ultrastructural study of human liver biopsy specimens we found that peroxisomes are regularly present in normal human hepatocytes. Their relationships with the endoplasmic reticulum observed in other species and in other organs were also demonstrable in this material. Some normal peroxisomes were found to display marginal plates or peripheral crystalline inclusions which were present in pathologic specimens as well. In certain inherited metabolic disorders (Menkes' steely hair disease, analbuminemia) the volume of the individual peroxisomes appeared to be considerably reduced. But most pathologic processes affecting hepatocytes seem to produce any or several of the following: increased volume or numbers per cell, changes of shapes, alterations of the consistency of the matrix, appearance of dense numbers per cell, changes of shapes, alterations of the consistency of the matrix, appearance of dense inclusions, or clustering of peroxisomes in some portions of the cytoplasm. Some of these abnormalities are reversible based on observations in three patients with Wilson's disease treated with D-penicillamine. The mean +/- standard deviation of diameters of peroxisomes in four normal subjects was 0.618 +/- 0.143 mum. Significant reductions or increases in mean diameters of peroxisomes were noted in all but two of the 16 pathologic specimens. There were other morphologic abnormalities present in the remaining two specimens. We conclude that various pathologic processes involving the hepatocytic cytoplasm exert different effects on peroxisomes. Although no specific pattern of morphologic alteration emerged from this exploratory study, a possible involvement of peroxisomes ought to be considered whenever metabolic or pathologic processes affect the liver."}
{"id": "PMID:190477", "title": "Symptoms and signs of cancer in the school-age child.", "content": "The American Cancer Society's seven warning signs of cancer are: 1. Unusual bleeding or discharge. 2. A lump or thickening in the breast or elsewhere. 3. A sore that does not heal. 4. Change in bowel or bladder habits. 5. Hoarseness or cough. 6. Indigestion or difficulty in swallowing. 7. Change in size or color of a wart or mole. These signs apply to children as well as to adults. Cancer in children, however, is often more insidious than in adults and may well mimic many other diseases, developmental processess, or childhood psychologic problems. The knowledge that cancer kills more children than any other disease and the awareness of the presenting symptoms and signs may well save a child's life. Early detection with prompt, aggressive therapy is of paramount importance in achieving cures in childhood cancer.", "contents": "Symptoms and signs of cancer in the school-age child. The American Cancer Society's seven warning signs of cancer are: 1. Unusual bleeding or discharge. 2. A lump or thickening in the breast or elsewhere. 3. A sore that does not heal. 4. Change in bowel or bladder habits. 5. Hoarseness or cough. 6. Indigestion or difficulty in swallowing. 7. Change in size or color of a wart or mole. These signs apply to children as well as to adults. Cancer in children, however, is often more insidious than in adults and may well mimic many other diseases, developmental processess, or childhood psychologic problems. The knowledge that cancer kills more children than any other disease and the awareness of the presenting symptoms and signs may well save a child's life. Early detection with prompt, aggressive therapy is of paramount importance in achieving cures in childhood cancer."}
{"id": "PMID:190479", "title": "Obesity obscuring breast cancer: a case report.", "content": "There is normally a layer of fat in the breast between the parenchyma of the breast and the skin. This is frequently thin and does not preclude the palpation of a tumor mass which involves the breast parenchyma. In patients suffering from obesity this fat pad becomes much thicker and obscures any underlying masses arising from the breast parenchyma. A case is reported in which a woman who was markedly obese lost a significant amount of weight and presented a bulge which was found to be carcinoma. This situation, in which fat obscures underlying breast lesion, has been observed in a number of patients. Attention is called to the limited value of physical examination of the breast in markedly obese patients. If any suspicion exists or if the patient is a candidate for cancer from a familial standpoint, mammograms are indicated.", "contents": "Obesity obscuring breast cancer: a case report. There is normally a layer of fat in the breast between the parenchyma of the breast and the skin. This is frequently thin and does not preclude the palpation of a tumor mass which involves the breast parenchyma. In patients suffering from obesity this fat pad becomes much thicker and obscures any underlying masses arising from the breast parenchyma. A case is reported in which a woman who was markedly obese lost a significant amount of weight and presented a bulge which was found to be carcinoma. This situation, in which fat obscures underlying breast lesion, has been observed in a number of patients. Attention is called to the limited value of physical examination of the breast in markedly obese patients. If any suspicion exists or if the patient is a candidate for cancer from a familial standpoint, mammograms are indicated."}
{"id": "PMID:190480", "title": "Cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) in lymphocytes from patients with stage III and IV squamous cell carcinoma of the head and neck.", "content": "In vivo skin tests using multiple recall and primary antigens such as dinitrochlorobenzine (DNCB) have established that there is decreased cellular-mediated immune response in patients with squamous cell carcinomas of the head and neck. In vitro testing of lymphocytes using blastogenic mitogens as a measure of lymphocyte function has not always shown a statistical difference between patients and controls.cAMP-PDE was assayed in lymphocytes from normal controls-patients with benign conditions in various age groups. No significant difference was found in the specific activity (Vmax) or affinity (Km) in these groups. The mean average was used as a normal control value. In lymphocytes from untreated patients with Stage III and IV squamous cell carcinomas of the head and neck, the Vmax and Km of cAMP-PDE were higher than the controls. This difference was statistically significant. Postoperative values were also determined byt were not statistically different. There were no differences found in blastogenesis in these two groups.", "contents": "Cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) in lymphocytes from patients with stage III and IV squamous cell carcinoma of the head and neck. In vivo skin tests using multiple recall and primary antigens such as dinitrochlorobenzine (DNCB) have established that there is decreased cellular-mediated immune response in patients with squamous cell carcinomas of the head and neck. In vitro testing of lymphocytes using blastogenic mitogens as a measure of lymphocyte function has not always shown a statistical difference between patients and controls.cAMP-PDE was assayed in lymphocytes from normal controls-patients with benign conditions in various age groups. No significant difference was found in the specific activity (Vmax) or affinity (Km) in these groups. The mean average was used as a normal control value. In lymphocytes from untreated patients with Stage III and IV squamous cell carcinomas of the head and neck, the Vmax and Km of cAMP-PDE were higher than the controls. This difference was statistically significant. Postoperative values were also determined byt were not statistically different. There were no differences found in blastogenesis in these two groups."}
{"id": "PMID:190481", "title": "Paget's disease of the breast.", "content": "Twenty-nine histologically verified cases of Paget's disease of the breast treated at the Hadassah University Hospital in the years 1949-1972 were followed up and analyzed. Dividing this material into two groups according to the presence or absence of a palpable breast tumor revealed significant difference in behavior and survival. Patients with a breast mass (34%) had a 50% axillary lymph node involvement and behaved as with any other ordinary breast cancer, with a 5-year survival rate of 40% and a 10-year survival rate of 33%. Patients with no palpable breast mass (66%) had only a 10.5% lymph node involvement, the 5-year survival rate being 94% and the 10-year survival rate being 91%. Delay in diagnosis seems to play no significant factor in survival rates and outcome. We believe radical mastectomy to be the treatment of choice in all cases of Paget's disease of the breast.", "contents": "Paget's disease of the breast. Twenty-nine histologically verified cases of Paget's disease of the breast treated at the Hadassah University Hospital in the years 1949-1972 were followed up and analyzed. Dividing this material into two groups according to the presence or absence of a palpable breast tumor revealed significant difference in behavior and survival. Patients with a breast mass (34%) had a 50% axillary lymph node involvement and behaved as with any other ordinary breast cancer, with a 5-year survival rate of 40% and a 10-year survival rate of 33%. Patients with no palpable breast mass (66%) had only a 10.5% lymph node involvement, the 5-year survival rate being 94% and the 10-year survival rate being 91%. Delay in diagnosis seems to play no significant factor in survival rates and outcome. We believe radical mastectomy to be the treatment of choice in all cases of Paget's disease of the breast."}
{"id": "PMID:190487", "title": "[Mixed plantar tumor clinically simulating eccrine poroma].", "content": "The case of a 39 years old female patient suffering from a painful, ulcerated nodule on the sole of her left foot for the last 15 months is presented. Clinically, for its localization and resemblance to a pyogenic granuloma, the lesion was considered to be an eccrine poroma. However its depth and tense, cystic feeling on palpation, were considered somewhat unusual. Microscopically the lesion was a \"mixed tumour\" of the salivary type with ductal differentiation and no cartilage formation. Seven other cases of plantar \"mixed tumours\" were gathered from the literature but neither ulceration nor poroma looking features were mentioned in any of them.", "contents": "[Mixed plantar tumor clinically simulating eccrine poroma]. The case of a 39 years old female patient suffering from a painful, ulcerated nodule on the sole of her left foot for the last 15 months is presented. Clinically, for its localization and resemblance to a pyogenic granuloma, the lesion was considered to be an eccrine poroma. However its depth and tense, cystic feeling on palpation, were considered somewhat unusual. Microscopically the lesion was a \"mixed tumour\" of the salivary type with ductal differentiation and no cartilage formation. Seven other cases of plantar \"mixed tumours\" were gathered from the literature but neither ulceration nor poroma looking features were mentioned in any of them."}
{"id": "PMID:190483", "title": "[Krukenberg's tumor of the ovary and uterine myoma].", "content": "A case of Krukenberg's tumour of the ovary in a 41-year-old patient is described. A year before admission she had mild gastric trouble, repeated short-lasting amenorrhea followed by prolonged bleeding. The menstruations preceding hospitalization were normal and painless. More serious trouble developed suddenly, four days before admission, in the form of intense pain in the lower abdomen and moderate bleeding. The woman had delivered twice and had 6 abortions. Her mother died of intestinal cancer. On examination, the patient was found to have two tumours: one on the right side, the size of a newborn's head, and one on the left side, the size of a female fist, both kidney-shaped and mobile. Also numerous small knots on the small intestine, peritoneum, and omentum, as well as a considerable amount of ascites were observed. An uterine myoma was found as well. Histerectomy and ablation of both adnexa were performed. The therapy was continued by radiation but the patient died 5 months following the operation.", "contents": "[Krukenberg's tumor of the ovary and uterine myoma]. A case of Krukenberg's tumour of the ovary in a 41-year-old patient is described. A year before admission she had mild gastric trouble, repeated short-lasting amenorrhea followed by prolonged bleeding. The menstruations preceding hospitalization were normal and painless. More serious trouble developed suddenly, four days before admission, in the form of intense pain in the lower abdomen and moderate bleeding. The woman had delivered twice and had 6 abortions. Her mother died of intestinal cancer. On examination, the patient was found to have two tumours: one on the right side, the size of a newborn's head, and one on the left side, the size of a female fist, both kidney-shaped and mobile. Also numerous small knots on the small intestine, peritoneum, and omentum, as well as a considerable amount of ascites were observed. An uterine myoma was found as well. Histerectomy and ablation of both adnexa were performed. The therapy was continued by radiation but the patient died 5 months following the operation."}
{"id": "PMID:190492", "title": "Surgical management of nasopharyngeal angiofibroma with intracranial extension.", "content": "Intracranial extension of nasopharyngeal angiofibroma is a condition difficult to diagnose and even more difficult to treat. Often the diagnosis is not suspected until autopsy. The management of intracranial extension has included incomplete removal via the extracranial approach, radiation therapy, hormonal therapy and cryosurgery. The results of these therapeutic efforts have been characterized by persistent tumor, severe hemorrhage, intracranial complications and death. The combined intra-extracranial approach shows some promise of total tumor removal in the patient with intracranial extension with minimal morbidity. The general criteria of patient selection, risks, surgical technique and case histories of two patients are presented.", "contents": "Surgical management of nasopharyngeal angiofibroma with intracranial extension. Intracranial extension of nasopharyngeal angiofibroma is a condition difficult to diagnose and even more difficult to treat. Often the diagnosis is not suspected until autopsy. The management of intracranial extension has included incomplete removal via the extracranial approach, radiation therapy, hormonal therapy and cryosurgery. The results of these therapeutic efforts have been characterized by persistent tumor, severe hemorrhage, intracranial complications and death. The combined intra-extracranial approach shows some promise of total tumor removal in the patient with intracranial extension with minimal morbidity. The general criteria of patient selection, risks, surgical technique and case histories of two patients are presented."}
{"id": "PMID:190493", "title": "Transpalatal approach to deeper cranial structures.", "content": "The approach to deep midline cranial structures is technically difficult. The transpalatal approach has a relatively wide exposure as compared to the transnasal, transantral and transethmoidal approches. The added advantage of a medial approach which follows medial landmarks and the flexibility of being able to extend exposure to the maxillary sinuses and pterygomaxillary space makes this an attractive approach for large lesions in the nasal passages, nasopharynx and sphenoid sinuses. Large mucoperiosteal flaps, care to avoid the palatine vessels, and application of palatal splint postoperatively, minimize complications and patient discomfort. The authors have used this approach to repair nasopharyngeal atresia, remove nasopharyngeal angiofibromas, approach the pituitary, craniopharyngioma and isolated sphenoid sinus opacification as well as sphenoid sinusitis with cavernous sinus thrombosis.", "contents": "Transpalatal approach to deeper cranial structures. The approach to deep midline cranial structures is technically difficult. The transpalatal approach has a relatively wide exposure as compared to the transnasal, transantral and transethmoidal approches. The added advantage of a medial approach which follows medial landmarks and the flexibility of being able to extend exposure to the maxillary sinuses and pterygomaxillary space makes this an attractive approach for large lesions in the nasal passages, nasopharynx and sphenoid sinuses. Large mucoperiosteal flaps, care to avoid the palatine vessels, and application of palatal splint postoperatively, minimize complications and patient discomfort. The authors have used this approach to repair nasopharyngeal atresia, remove nasopharyngeal angiofibromas, approach the pituitary, craniopharyngioma and isolated sphenoid sinus opacification as well as sphenoid sinusitis with cavernous sinus thrombosis."}
{"id": "PMID:190495", "title": "Unusual parotid tumors.", "content": "The patient presenting with a mass lesion of the parotid gland is frequently found to have a mixed tumor of salivary tissue origin. However, less common lesions occur in the anatomical region of the parotid gland. These pathological entities deserve consideration in the differential diagnosis. This report presents nine patients with unusual lesions occurring in the parotid region. These regions include cervicofacial actinomycosis, branchial cleft cyst, parapharyngeal tumors, bony lesion of the mandible, non-parotid origin malignant tumor, and metastatic malignant tumors. Each class of lesions demonstrated is also discussed.", "contents": "Unusual parotid tumors. The patient presenting with a mass lesion of the parotid gland is frequently found to have a mixed tumor of salivary tissue origin. However, less common lesions occur in the anatomical region of the parotid gland. These pathological entities deserve consideration in the differential diagnosis. This report presents nine patients with unusual lesions occurring in the parotid region. These regions include cervicofacial actinomycosis, branchial cleft cyst, parapharyngeal tumors, bony lesion of the mandible, non-parotid origin malignant tumor, and metastatic malignant tumors. Each class of lesions demonstrated is also discussed."}
{"id": "PMID:190496", "title": "Cranial neuropathies in sinus disease.", "content": "To study the problem of cranial neuropathies in sinus disease the inpatient experience at the University of California, San Francisco, and San Francisco General Hospitals was reviewed. The incidence of cranial nerve involvement in acute and chronic sinus inflammations was low (8 percent and 4 percent respectively). The incidence in neoplastic disease of the sinuses was considerably higher (32 percent). Cranial neuropathies occurred in inflammatory disease more frequently when associated with mucopyocele, mucormycosis, and orbital cellulitis. In both inflammatory and neoplastic disease, when cranial nerve deficits occurred, there was a high predelication for sphenoid sinus involvement. Several instructive case histories are included. The important anatomy of the cavernous sinus region and of the orbital apex as it pertains to this problem is discussed.", "contents": "Cranial neuropathies in sinus disease. To study the problem of cranial neuropathies in sinus disease the inpatient experience at the University of California, San Francisco, and San Francisco General Hospitals was reviewed. The incidence of cranial nerve involvement in acute and chronic sinus inflammations was low (8 percent and 4 percent respectively). The incidence in neoplastic disease of the sinuses was considerably higher (32 percent). Cranial neuropathies occurred in inflammatory disease more frequently when associated with mucopyocele, mucormycosis, and orbital cellulitis. In both inflammatory and neoplastic disease, when cranial nerve deficits occurred, there was a high predelication for sphenoid sinus involvement. Several instructive case histories are included. The important anatomy of the cavernous sinus region and of the orbital apex as it pertains to this problem is discussed."}
{"id": "PMID:190497", "title": "Evidence for an etiologic relation of the Epstein-Barr virus to human malignancies.", "content": "Studies on virus-induced animal tumors have provided indirect approaches to a search for viruses causing human malignancies. Epstein-Barr virus (EBV), the cause of infectious mononucleosis, served to illustrate the usefulness of these approaches in linking EBV with Burkitt's lymphoma and nasopharyngeal carcinoma. Despite its demonstrated intimate association with these tumors the role of EBV in their causation remains uncertain. While a passenger role seems excluded, it cannot be decided whether EBV is the primary or a secondary agent in the etiology of the tumors. If the primary cause, immunologic, genetic, virologic or other environmental factors are undoubtedly needed for EBV to express its obvious oncogenic potential. The data illustrate the difficulties encountered in proving a viral etiology of human malignancies.", "contents": "Evidence for an etiologic relation of the Epstein-Barr virus to human malignancies. Studies on virus-induced animal tumors have provided indirect approaches to a search for viruses causing human malignancies. Epstein-Barr virus (EBV), the cause of infectious mononucleosis, served to illustrate the usefulness of these approaches in linking EBV with Burkitt's lymphoma and nasopharyngeal carcinoma. Despite its demonstrated intimate association with these tumors the role of EBV in their causation remains uncertain. While a passenger role seems excluded, it cannot be decided whether EBV is the primary or a secondary agent in the etiology of the tumors. If the primary cause, immunologic, genetic, virologic or other environmental factors are undoubtedly needed for EBV to express its obvious oncogenic potential. The data illustrate the difficulties encountered in proving a viral etiology of human malignancies."}
{"id": "PMID:190498", "title": "[TDI determination in polyurethane paints and in work environment (author's transl)].", "content": "A simple gas chromatographic method is described for the analytical determination of free monomeric TDL in polyurethane paints. Analyses of commercial products used in furniture plants showed a high percentage of free monomer with repercussion on the air and work environment.", "contents": "[TDI determination in polyurethane paints and in work environment (author's transl)]. A simple gas chromatographic method is described for the analytical determination of free monomeric TDL in polyurethane paints. Analyses of commercial products used in furniture plants showed a high percentage of free monomer with repercussion on the air and work environment."}
{"id": "PMID:190499", "title": "[The relation of infection with the hepatitis B-agent to primary hepatic carcinoma (author's transl)].", "content": "In Asia, Africa and other tropical areas primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the post-necrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 PHC patients had hepatitis B surface antigen (HBSAg) (controls: 8 of 98) and 56 of 63 (controls: 26 of 100) had antibody against hepatitis B core antigen (anti-HBC). In earlier studies we demonstrated a maternal effect of HBSAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBSAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; p = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBSAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the African hepatoma patients showed that there is a very high frequency of HBSAg in mothers (71.6%) while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. We described a vaccine several years ago which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population.", "contents": "[The relation of infection with the hepatitis B-agent to primary hepatic carcinoma (author's transl)]. In Asia, Africa and other tropical areas primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the post-necrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 PHC patients had hepatitis B surface antigen (HBSAg) (controls: 8 of 98) and 56 of 63 (controls: 26 of 100) had antibody against hepatitis B core antigen (anti-HBC). In earlier studies we demonstrated a maternal effect of HBSAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBSAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; p = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBSAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the African hepatoma patients showed that there is a very high frequency of HBSAg in mothers (71.6%) while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. We described a vaccine several years ago which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population."}
{"id": "PMID:190500", "title": "[Serum lactic dehydrogenase isoenzymes in metastatic and primary liver carcinoma (author's transl)].", "content": "Serum LDH isoenzymes were comparatively evaluated in experimental and human liver carcinoma. In our experimental studies, LDH4 increased in AH 66 F metastatic hepatic cancer, but DAB hepatic cancer showed a significant increase of LDH5. In clinical studies, LDH4 and LDH5 increased significantly in metastatic liver carcinoma, and 15 (79%) out of 19 cases showed higher values of LDH4. In primary liver carcinoma LDH5 increased significantly, and 12 (92%) out of 13 cases showed a higher LDH5. Therefore, analyses of serum LDH isoenzymes would aid in differential diagnosis of metastatic and primary liver carcinoma.", "contents": "[Serum lactic dehydrogenase isoenzymes in metastatic and primary liver carcinoma (author's transl)]. Serum LDH isoenzymes were comparatively evaluated in experimental and human liver carcinoma. In our experimental studies, LDH4 increased in AH 66 F metastatic hepatic cancer, but DAB hepatic cancer showed a significant increase of LDH5. In clinical studies, LDH4 and LDH5 increased significantly in metastatic liver carcinoma, and 15 (79%) out of 19 cases showed higher values of LDH4. In primary liver carcinoma LDH5 increased significantly, and 12 (92%) out of 13 cases showed a higher LDH5. Therefore, analyses of serum LDH isoenzymes would aid in differential diagnosis of metastatic and primary liver carcinoma."}
{"id": "PMID:190501", "title": "[Multiple nodular densities on chest X-ray in liver cirrhosis--a diagnostic problem? (author's transl)].", "content": "A case report is given of a 49 year old white male patient, who had suffered for several years from liver cirrhosis and who finally died from hepatoma. Although a hepatoma was suspected in this case it was not demonstrated intra vitam, though at autopsy it was found to have invaded the lower vena cava, continuing into the right atrium. Problems of early diagnosis of hepatoma are discussed in context with this case.", "contents": "[Multiple nodular densities on chest X-ray in liver cirrhosis--a diagnostic problem? (author's transl)]. A case report is given of a 49 year old white male patient, who had suffered for several years from liver cirrhosis and who finally died from hepatoma. Although a hepatoma was suspected in this case it was not demonstrated intra vitam, though at autopsy it was found to have invaded the lower vena cava, continuing into the right atrium. Problems of early diagnosis of hepatoma are discussed in context with this case."}
{"id": "PMID:190502", "title": "[Adrenergic receptors in the pathogenesis of congenital megacolon (author's transl)].", "content": "Contractions of fresh specimens of taenial musculature from human colon were investigated under the influence of depolarization (bathing in solutions high in potassium), of acetylcholine, and of adrenaline; definite changes of contractile tension could be induced by these agents. The investigations were carried out using normal musculature as well as specimens from patients with congenital megacolon taken from the narrow segment. Contractions after depolarization and after cholinergic stimulation were equal in all specimens investigated, pre-extension of these specimens not differing significantly. Relaxation of colon musculature mediated by adrenergic receptors was very pronounced in normal musculature, but was lacking in specimens taken from the narrow segments of congenital megacolon. Sympathetic stimulation of normal taenial musculature does abolish completely cholinergically induced contractions. On the other hand, a preparation relaxed by adrenaline contracts very little after additional application of acetylcholine. These findings do suggest a severe disturbance of adrenergic receptors in the colon, or of adrenergic neuromuscular transmission in congenital megacolon.", "contents": "[Adrenergic receptors in the pathogenesis of congenital megacolon (author's transl)]. Contractions of fresh specimens of taenial musculature from human colon were investigated under the influence of depolarization (bathing in solutions high in potassium), of acetylcholine, and of adrenaline; definite changes of contractile tension could be induced by these agents. The investigations were carried out using normal musculature as well as specimens from patients with congenital megacolon taken from the narrow segment. Contractions after depolarization and after cholinergic stimulation were equal in all specimens investigated, pre-extension of these specimens not differing significantly. Relaxation of colon musculature mediated by adrenergic receptors was very pronounced in normal musculature, but was lacking in specimens taken from the narrow segments of congenital megacolon. Sympathetic stimulation of normal taenial musculature does abolish completely cholinergically induced contractions. On the other hand, a preparation relaxed by adrenaline contracts very little after additional application of acetylcholine. These findings do suggest a severe disturbance of adrenergic receptors in the colon, or of adrenergic neuromuscular transmission in congenital megacolon."}
{"id": "PMID:190518", "title": "The association of oral androgenic-anabolic steroids and life-threatening disease.", "content": "The use of androgenic anabolic steroids in the therapeutic dose range by strength athletes is well documented. The benign side effects of these drugs are well known but more disturbing are the increasingly frequent reports of potentially fatal diseases in association with the therapeutic use of these agents. A review is made of the clinical evidence indicating a direct association between androgenic steroids and peliosis hepatis, heptocellular carcinoma and acute myelogenous leukemia, all potentially fatal disorders.", "contents": "The association of oral androgenic-anabolic steroids and life-threatening disease. The use of androgenic anabolic steroids in the therapeutic dose range by strength athletes is well documented. The benign side effects of these drugs are well known but more disturbing are the increasingly frequent reports of potentially fatal diseases in association with the therapeutic use of these agents. A review is made of the clinical evidence indicating a direct association between androgenic steroids and peliosis hepatis, heptocellular carcinoma and acute myelogenous leukemia, all potentially fatal disorders."}
{"id": "PMID:190522", "title": "Measurement of antibodies to Herpesvirus hominis by indirect immunofluorescent antibody method.", "content": "Antibodies to Herpesvirus hominis (HVH) were evaluated by indirect immunofluorescent antibody (FA) method. Frozen sections of HVH infected mouse brain provided antigens for FA staining. Our data indicate that indirect FA staining is a rapid, sensitive, and reproducible method for measurement of antibodies to HVH. Indirect FA method can be applied as an additional tool for the measurement of antibodies to HVH and can be applied for epidemiological survey of HVH infections.", "contents": "Measurement of antibodies to Herpesvirus hominis by indirect immunofluorescent antibody method. Antibodies to Herpesvirus hominis (HVH) were evaluated by indirect immunofluorescent antibody (FA) method. Frozen sections of HVH infected mouse brain provided antigens for FA staining. Our data indicate that indirect FA staining is a rapid, sensitive, and reproducible method for measurement of antibodies to HVH. Indirect FA method can be applied as an additional tool for the measurement of antibodies to HVH and can be applied for epidemiological survey of HVH infections."}
{"id": "PMID:190525", "title": "[The index of leukocyte alkaline phosphatase in patients with hemodialysis (author's transl)].", "content": "The index of the leukocyte alkaline phosphatase activity (LAP-I) was evaluated in 15 patients suffering from chronic uremia immediately before and after hemodialysis, as well as 16 or 18 and 40 or 42 hours thereafter. Immediately following hemodialysis the LAP-I was significantly reduced in comparison with to predialysis values. 16 and 18 hours after hemodialysis the LAP-I had again increased and at 40 and 42 hours exceeded the starting predialysis values. These results are discussed in relation to the dialysis-induced decrease of plasma cortisol and to the consequent ACTH and cortisol overproduction.", "contents": "[The index of leukocyte alkaline phosphatase in patients with hemodialysis (author's transl)]. The index of the leukocyte alkaline phosphatase activity (LAP-I) was evaluated in 15 patients suffering from chronic uremia immediately before and after hemodialysis, as well as 16 or 18 and 40 or 42 hours thereafter. Immediately following hemodialysis the LAP-I was significantly reduced in comparison with to predialysis values. 16 and 18 hours after hemodialysis the LAP-I had again increased and at 40 and 42 hours exceeded the starting predialysis values. These results are discussed in relation to the dialysis-induced decrease of plasma cortisol and to the consequent ACTH and cortisol overproduction."}
{"id": "PMID:190530", "title": "A gal region mutant that requires cAMP for growth on galactose in an adenyl cyclase negative (cya delta) background.", "content": "Strains of Escherichia coli K12 that contain a deletion of the adenyl cyclase gen (cya delta), required for the synthesis of cyclic adenosine-3';5' monophosphate (cAMP), grow on galactose-containing minimal medium. A mutant was isolated that grows on this medium only if cAMP is added. The mutation (designated galP20) is linked to the gal operon region as determined by both generalized transduction with bacteriophage P1 and specialized transduction with bacteriophage lambda. Studies with galP20 cya delta strains as well as gal delta (deletions of the gal operon) cya delta strains indicate that synthesis of the physiologically important transport mechanism for galactose (galactose permease) requires either cAMP or a function mission from both the galdelta strains and the galP20 strain.", "contents": "A gal region mutant that requires cAMP for growth on galactose in an adenyl cyclase negative (cya delta) background. Strains of Escherichia coli K12 that contain a deletion of the adenyl cyclase gen (cya delta), required for the synthesis of cyclic adenosine-3';5' monophosphate (cAMP), grow on galactose-containing minimal medium. A mutant was isolated that grows on this medium only if cAMP is added. The mutation (designated galP20) is linked to the gal operon region as determined by both generalized transduction with bacteriophage P1 and specialized transduction with bacteriophage lambda. Studies with galP20 cya delta strains as well as gal delta (deletions of the gal operon) cya delta strains indicate that synthesis of the physiologically important transport mechanism for galactose (galactose permease) requires either cAMP or a function mission from both the galdelta strains and the galP20 strain."}
{"id": "PMID:190531", "title": "[Adrenocortical adenoma in a 2 1/2 year old girl causing virilization and accelerated growth. Clinical and morphological results (author's transl)].", "content": "A 2 1/2 year old girl with virilization and advanced bone age was found to have a leftsided adrenocortical adenoma. The secretion of mainly androgens besides estrogens was not suppressible with dexamethasone. Plasma cortisol levels were not elevated but did not show any circadian rhythm. The tumor was localized by retroperitoneal instillation of gas, intravenous urography and tomography. After complete removal of the tumor the originally strongly elevated excretion of 17-ketosteroids sank back to normal, the acceleration of skeletal development slowed down. The right adrenal cortex was not atrophic, 2 1/2 years after the operation the child is well and without evidence of recurrent disease. Differential diagnosis as well as ultrastructor and histology of the tumor are discussed with reference to the literature.", "contents": "[Adrenocortical adenoma in a 2 1/2 year old girl causing virilization and accelerated growth. Clinical and morphological results (author's transl)]. A 2 1/2 year old girl with virilization and advanced bone age was found to have a leftsided adrenocortical adenoma. The secretion of mainly androgens besides estrogens was not suppressible with dexamethasone. Plasma cortisol levels were not elevated but did not show any circadian rhythm. The tumor was localized by retroperitoneal instillation of gas, intravenous urography and tomography. After complete removal of the tumor the originally strongly elevated excretion of 17-ketosteroids sank back to normal, the acceleration of skeletal development slowed down. The right adrenal cortex was not atrophic, 2 1/2 years after the operation the child is well and without evidence of recurrent disease. Differential diagnosis as well as ultrastructor and histology of the tumor are discussed with reference to the literature."}
{"id": "PMID:190529", "title": "ESR spectra of quasirandomly oriented centers: application to radiation damage centers in bone.", "content": "The angular dependence of the ESR line shape from polycrystalline samples due to incomplete randomness in the orientation of the crystallites is calculated for centers with axial symmetry. The effect of a preferential axis of orientation is considered and the results are applied to radiation produce centers in bone.", "contents": "ESR spectra of quasirandomly oriented centers: application to radiation damage centers in bone. The angular dependence of the ESR line shape from polycrystalline samples due to incomplete randomness in the orientation of the crystallites is calculated for centers with axial symmetry. The effect of a preferential axis of orientation is considered and the results are applied to radiation produce centers in bone."}
{"id": "PMID:190533", "title": "Pesticide induced DNA damage and its repair in cultured human cells.", "content": "The effects of pesticides on the induction of unscheduled DNA synthesis in SV-40 transformed human cells (VA-4) in culture with and without metabolic activation by liver microsomes was studied. Results showed that ten of the thirteen compounds examined either directly or upon metabolic activation induced unscheduled DNA synthesis in the human cell system used. The DNA repair kinetics and size of the repaired regions resulting from treatment with four of the chemicals (Carbaryl, Chlordane, Dieldrin and 2.4-D Fluid) were studied by 313 nm photolysis of repaired regions containing bromodeoxyuridine (BUdR). The size of the repaired regions differed between compounds but could generally be classified as either of the X-ray (short) or UV-type (long).", "contents": "Pesticide induced DNA damage and its repair in cultured human cells. The effects of pesticides on the induction of unscheduled DNA synthesis in SV-40 transformed human cells (VA-4) in culture with and without metabolic activation by liver microsomes was studied. Results showed that ten of the thirteen compounds examined either directly or upon metabolic activation induced unscheduled DNA synthesis in the human cell system used. The DNA repair kinetics and size of the repaired regions resulting from treatment with four of the chemicals (Carbaryl, Chlordane, Dieldrin and 2.4-D Fluid) were studied by 313 nm photolysis of repaired regions containing bromodeoxyuridine (BUdR). The size of the repaired regions differed between compounds but could generally be classified as either of the X-ray (short) or UV-type (long)."}
{"id": "PMID:190534", "title": "Inhibition of initiation of HeLa cell replicons by methyl methanesulfonate.", "content": "Methyl methanesulfonate (MMS) in the culture medium inhibits the rate of DNA synthesis in HeLa cells in a dose-dependent manner. By using short (5 min) incubations with [3H]thymidine and analyzing the newly made DNA by velocity sedimentation on alkaline sucrose gradients, we found that the first affect of MMS on DNA replication, at 0.5 h after treatment, was inhibition of initiation of replicons. Recovery from this effect seemed to have begun by 2 3/4 h after treatment. The second effect of MMS, which was evident at 2 h after treatment, was to slow or block chain elongation.", "contents": "Inhibition of initiation of HeLa cell replicons by methyl methanesulfonate. Methyl methanesulfonate (MMS) in the culture medium inhibits the rate of DNA synthesis in HeLa cells in a dose-dependent manner. By using short (5 min) incubations with [3H]thymidine and analyzing the newly made DNA by velocity sedimentation on alkaline sucrose gradients, we found that the first affect of MMS on DNA replication, at 0.5 h after treatment, was inhibition of initiation of replicons. Recovery from this effect seemed to have begun by 2 3/4 h after treatment. The second effect of MMS, which was evident at 2 h after treatment, was to slow or block chain elongation."}
{"id": "PMID:190537", "title": "Possible role of renin in hypertension as suggested by renin-sodium profiling and inhibition of converting enzyme.", "content": "To block renin activity, a nonapeptide converting-enzyme inhibitor was given to 65 seated hypertensive patients. Depressor responses occurred only when control plasma renin activity exceeded 2 ng of angiotensin I per milliliter per hour and correlated directly in amplitude with control plasma renin activity and with induced increments in activity (P less than 0.001 for both). Depressor responses, like renin activity, were characteristic for renin subgroups as defined by renin-sodium profiling. Before and after sodium deprivation, the nonapeptide reduced diastolic pressure in all patients with high renin (by 17.3 and 19.8 per cent) and most patients with normal renin (by 9.1 and 17.7 per cent). Low-renin patients remained unresponsive. This enzyme blockade may cause bradykinin accumulation. But if, as seems likely, depressor responses are due to blockade of angiotensin II formation, the results indicate that, irrespective of sodium balance, measurements of plasma renin activity reflect its contribution to blood-pressure maintenance. The results suggest broad participation of the renin system in common forms of hypertension.", "contents": "Possible role of renin in hypertension as suggested by renin-sodium profiling and inhibition of converting enzyme. To block renin activity, a nonapeptide converting-enzyme inhibitor was given to 65 seated hypertensive patients. Depressor responses occurred only when control plasma renin activity exceeded 2 ng of angiotensin I per milliliter per hour and correlated directly in amplitude with control plasma renin activity and with induced increments in activity (P less than 0.001 for both). Depressor responses, like renin activity, were characteristic for renin subgroups as defined by renin-sodium profiling. Before and after sodium deprivation, the nonapeptide reduced diastolic pressure in all patients with high renin (by 17.3 and 19.8 per cent) and most patients with normal renin (by 9.1 and 17.7 per cent). Low-renin patients remained unresponsive. This enzyme blockade may cause bradykinin accumulation. But if, as seems likely, depressor responses are due to blockade of angiotensin II formation, the results indicate that, irrespective of sodium balance, measurements of plasma renin activity reflect its contribution to blood-pressure maintenance. The results suggest broad participation of the renin system in common forms of hypertension."}
{"id": "PMID:190543", "title": "Structure of an antibody combining site by magnetic resonance.", "content": "The structure of the combining site of the DNP binding IgA mouse myeloma protein MOPC 315 has been determined by a combination of high resolution nuclear magnetic resonance, electron spin resonance, model building and chemical modifications. This approach yields that general dimensions of the site, its polarity and asymmetry features, the assignment of the DNP-contact residues and their three-dimensional coordinates.", "contents": "Structure of an antibody combining site by magnetic resonance. The structure of the combining site of the DNP binding IgA mouse myeloma protein MOPC 315 has been determined by a combination of high resolution nuclear magnetic resonance, electron spin resonance, model building and chemical modifications. This approach yields that general dimensions of the site, its polarity and asymmetry features, the assignment of the DNP-contact residues and their three-dimensional coordinates."}
{"id": "PMID:190546", "title": "Embryonic development and mitochondrial function. 2. Thiamphenicol induced embryotoxicity.", "content": "Inhibition of mitochondrial protein synthesis in rat embryos during late organogenesis leads to impaired embryonic development. 1. Thiamphenicol (TAP), similar to chloramphenicol, inhibits in vivo the synthesis of cytochrome oxidase (cytox), which is partially synthesized by the mitochondrion. Subsequently, DNA synthesis and embryonic growth are affected. 2. Embryos on day 10 and 11, in contrast to embryos on day 9 of gestation, show a high sensitivity of mitochondrial protein synthesis, measured as cytox activity. From day 10 onwards, such an inhibition leads to pronounced impairment of DNA synthesis. The rat hemochorial placenta starts functioning on day 12 of gestation. Larger doses of TAP are required to inhibit cytox and DNA synthesis for treatment after placentation rather than before placentation. 3. Dose-response relationships differ depending on the date and duration of treatment. Application of TAP for 1 day requires 10-30 mg/kg TAP to inhibit cytox synthesis and 60-100 mg/kg to impair embryonic growth. Prolongation of treatment to 4 days (day 10-13) lowers the dose required for inhibition of DNA synthesis to 10 mg TAP/kg/day. This is lower than the human therapeutic dose. Larger doses lead to embryolethality. 4. The extent of inhibition of DNA synthesis provoked by inhibition of mitochondrial protein synthesis depends on a number of factors which include: different growth rates during organogenesis, the number of mitochondria present prior to treatment, availability of extramitochondrial ATP sources and placental permeability barrier.", "contents": "Embryonic development and mitochondrial function. 2. Thiamphenicol induced embryotoxicity. Inhibition of mitochondrial protein synthesis in rat embryos during late organogenesis leads to impaired embryonic development. 1. Thiamphenicol (TAP), similar to chloramphenicol, inhibits in vivo the synthesis of cytochrome oxidase (cytox), which is partially synthesized by the mitochondrion. Subsequently, DNA synthesis and embryonic growth are affected. 2. Embryos on day 10 and 11, in contrast to embryos on day 9 of gestation, show a high sensitivity of mitochondrial protein synthesis, measured as cytox activity. From day 10 onwards, such an inhibition leads to pronounced impairment of DNA synthesis. The rat hemochorial placenta starts functioning on day 12 of gestation. Larger doses of TAP are required to inhibit cytox and DNA synthesis for treatment after placentation rather than before placentation. 3. Dose-response relationships differ depending on the date and duration of treatment. Application of TAP for 1 day requires 10-30 mg/kg TAP to inhibit cytox synthesis and 60-100 mg/kg to impair embryonic growth. Prolongation of treatment to 4 days (day 10-13) lowers the dose required for inhibition of DNA synthesis to 10 mg TAP/kg/day. This is lower than the human therapeutic dose. Larger doses lead to embryolethality. 4. The extent of inhibition of DNA synthesis provoked by inhibition of mitochondrial protein synthesis depends on a number of factors which include: different growth rates during organogenesis, the number of mitochondria present prior to treatment, availability of extramitochondrial ATP sources and placental permeability barrier."}
{"id": "PMID:190547", "title": "[Effect of ammonium acetate on depolarization processes in the central terminals of primary afferents].", "content": "Experiments on cats determined that ammonium acetate injected intravenously (2-4 mM/kg) supressed the processes of primary afferent depolarization (PAD) which are thought to be responsible for the presynaptic inhibition of spinal reflexes. The supression was transient and proceeded in paralle to depression of postsynaptic inhibition of monosynaptic reflexes. Ammonium acetate slightly decreased the amplitude of the negative postsynaptic potentials recorded form the dorsal surface of lumbar cord in response to stimulation of hind limb afferent nerves and increased polysynaptic reflex discharges in appropriate ventral roots. These findings make it unlikely that the ammonium depression of PAD is a result of impairment of interneuronal activity. A suggestion is made that ammonium depression of PAD results from diminition of the EMF for synaptic currents producing PAD.", "contents": "[Effect of ammonium acetate on depolarization processes in the central terminals of primary afferents]. Experiments on cats determined that ammonium acetate injected intravenously (2-4 mM/kg) supressed the processes of primary afferent depolarization (PAD) which are thought to be responsible for the presynaptic inhibition of spinal reflexes. The supression was transient and proceeded in paralle to depression of postsynaptic inhibition of monosynaptic reflexes. Ammonium acetate slightly decreased the amplitude of the negative postsynaptic potentials recorded form the dorsal surface of lumbar cord in response to stimulation of hind limb afferent nerves and increased polysynaptic reflex discharges in appropriate ventral roots. These findings make it unlikely that the ammonium depression of PAD is a result of impairment of interneuronal activity. A suggestion is made that ammonium depression of PAD results from diminition of the EMF for synaptic currents producing PAD."}
{"id": "PMID:190548", "title": "Serum enzyme activity in bone tumors and osteomyelitis (LDH, GOT, GPT, CPK, CHE, ALP, AP, PP, ALD).", "content": "Enzyme activity of lactate dehydrogenase, glutamate-oxalacetate and glutamate-pyruvate transaminase, creatine phosphokinase, cholinesterase, alkaline, acid and prostatic phosphatase and aldolase has been studied in a total of 213 subjects, of whom 97 were of good health, 63 had bone tumors and 53 suffered from osteomyelitis. The activities of the majority of the enzymes were found to become significantly changed in comparison with the norm. In both patient groups, the more striking differences being noted in that of osteomyelitis. However, enzymatic activity alone does not allow to differentiate the group of bone tumors from that of osteomyelitis, the differences between these two groups not being of significance in any one of the enzymes followed.", "contents": "Serum enzyme activity in bone tumors and osteomyelitis (LDH, GOT, GPT, CPK, CHE, ALP, AP, PP, ALD). Enzyme activity of lactate dehydrogenase, glutamate-oxalacetate and glutamate-pyruvate transaminase, creatine phosphokinase, cholinesterase, alkaline, acid and prostatic phosphatase and aldolase has been studied in a total of 213 subjects, of whom 97 were of good health, 63 had bone tumors and 53 suffered from osteomyelitis. The activities of the majority of the enzymes were found to become significantly changed in comparison with the norm. In both patient groups, the more striking differences being noted in that of osteomyelitis. However, enzymatic activity alone does not allow to differentiate the group of bone tumors from that of osteomyelitis, the differences between these two groups not being of significance in any one of the enzymes followed."}
{"id": "PMID:190549", "title": "Body temperature and tumor virus infection. I. Tumorogenicity of Rous sarcoma virus for reptiles.", "content": "Rous sarcoma virus (RSV) was oncogenic for the following nine species of reptiles representing 6 families from Chelonia and Squamata orders: family of Testudinidae: 1. Testudo horsfieldi, family Agamidae: 2. Agama sanguinolenta; 3. Agama erythrogastra, family Lacertidae: 4. Eremias persica; 5. Eremias velox; 6. Eremias grammica, family Scincidae: 7. Eumeces taeniolatus, family Boidea: 8. Erix tataricus, 9. Ancistrodom blomhoffi. RSV did not induce tumors in 13 studied species of reptiles. Histologically 26 reptile tumors studied were polymorphous sarcomas with spindle-shaped (fibroblast-like), round and polygonal macrophage-like cells and sometimes peculiar giant polynuclear cells. Chromosomal analysis showed that reptile tumors arose out of reptile cells. RSV was pathogenic for adult reptiles. Reptile tumors did not contain a mature infectious virus. The tumors of 2 snakes were virogenic. The effect of increased temperature at the body level on the transformation of a symptomless viral infection into a viral disease is discussed in the evolutionary aspect.", "contents": "Body temperature and tumor virus infection. I. Tumorogenicity of Rous sarcoma virus for reptiles. Rous sarcoma virus (RSV) was oncogenic for the following nine species of reptiles representing 6 families from Chelonia and Squamata orders: family of Testudinidae: 1. Testudo horsfieldi, family Agamidae: 2. Agama sanguinolenta; 3. Agama erythrogastra, family Lacertidae: 4. Eremias persica; 5. Eremias velox; 6. Eremias grammica, family Scincidae: 7. Eumeces taeniolatus, family Boidea: 8. Erix tataricus, 9. Ancistrodom blomhoffi. RSV did not induce tumors in 13 studied species of reptiles. Histologically 26 reptile tumors studied were polymorphous sarcomas with spindle-shaped (fibroblast-like), round and polygonal macrophage-like cells and sometimes peculiar giant polynuclear cells. Chromosomal analysis showed that reptile tumors arose out of reptile cells. RSV was pathogenic for adult reptiles. Reptile tumors did not contain a mature infectious virus. The tumors of 2 snakes were virogenic. The effect of increased temperature at the body level on the transformation of a symptomless viral infection into a viral disease is discussed in the evolutionary aspect."}
{"id": "PMID:190550", "title": "Effect of heterologous antimacrophage serum on growth of Rous virus-induced sarcoma in the allogeneic and syngeneic system.", "content": "The effect of heterologous antimacrophage serum (AMS) and normal rabbit serum (NRS) on the immune reaction against Rous virus-induced sarcoma (RSL) was studied in rats. The growth of RSL sarcoma transplanted against the H-1 barrier in AMS-treated rats was more progressive than in the untreated or NRS-treated control group. On the other hand, the growth of RSL sarcoma was significantly suppressed in syngeneic AMS- or NRS-treated recipients compared to the untreated control rats.", "contents": "Effect of heterologous antimacrophage serum on growth of Rous virus-induced sarcoma in the allogeneic and syngeneic system. The effect of heterologous antimacrophage serum (AMS) and normal rabbit serum (NRS) on the immune reaction against Rous virus-induced sarcoma (RSL) was studied in rats. The growth of RSL sarcoma transplanted against the H-1 barrier in AMS-treated rats was more progressive than in the untreated or NRS-treated control group. On the other hand, the growth of RSL sarcoma was significantly suppressed in syngeneic AMS- or NRS-treated recipients compared to the untreated control rats."}
{"id": "PMID:190553", "title": "Evidence of nycterohemeral periodicity in stress-induced pituitary-adrenal activation.", "content": "Plasma ACTH and corticosterone were measured under basal conditions and after ether or tourniquet stress during the nadir (a.m.) and zenith (p.m.) of the nycterohemeral pituitary-adrenal cycle. Exogenous ACTH was also given at these 2 times to assess adrenal sensitivity to ACTH and the maximal adrenal capacity for corticosterone secretion. Ether stress caused a greater rise in plasma ACTH in the a.m. than in the p.m., even though basal plasma ACTH and corticosterone concentrations were lower in the a.m. than in the p.m. When given in the p.m., pentobarbital anesthesia depressed plasma corticosterone and ACTH to the a.m. level; under these conditions the rise in plasma ACTH produced by tourniquet stress was the same in the a.m. and p.m. Both tourniquet and ether stresses caused maximal activation of adrenal corticosterone secretion, but ether produced a much greater rise in plasma ACTH. It is concluded that: (1) the greater ether-induced rise in plasma ACTH in the a.m. than in the p.m. is probably due to the lower plasma (and probably tissue) corticosterone concentration at that time; (2) the plasma ACTH concentration for inducing maximal adrenal activation is relatively low; and (3) the higher basal levels of plasma corticosterone in the p.m. than in the a.m. are due to a slight increase in basal ACTH secretion in the p.m.", "contents": "Evidence of nycterohemeral periodicity in stress-induced pituitary-adrenal activation. Plasma ACTH and corticosterone were measured under basal conditions and after ether or tourniquet stress during the nadir (a.m.) and zenith (p.m.) of the nycterohemeral pituitary-adrenal cycle. Exogenous ACTH was also given at these 2 times to assess adrenal sensitivity to ACTH and the maximal adrenal capacity for corticosterone secretion. Ether stress caused a greater rise in plasma ACTH in the a.m. than in the p.m., even though basal plasma ACTH and corticosterone concentrations were lower in the a.m. than in the p.m. When given in the p.m., pentobarbital anesthesia depressed plasma corticosterone and ACTH to the a.m. level; under these conditions the rise in plasma ACTH produced by tourniquet stress was the same in the a.m. and p.m. Both tourniquet and ether stresses caused maximal activation of adrenal corticosterone secretion, but ether produced a much greater rise in plasma ACTH. It is concluded that: (1) the greater ether-induced rise in plasma ACTH in the a.m. than in the p.m. is probably due to the lower plasma (and probably tissue) corticosterone concentration at that time; (2) the plasma ACTH concentration for inducing maximal adrenal activation is relatively low; and (3) the higher basal levels of plasma corticosterone in the p.m. than in the a.m. are due to a slight increase in basal ACTH secretion in the p.m."}
{"id": "PMID:190554", "title": "Correlation between hypothalamic catecholamine synthesis and ether stress-induced ACTH secretion.", "content": "The rates of synthesis of norepinephrine (NE) and dopamine (DA) in several regions of the hypothalamus have been estimated after exposure of rats to stresses that increase ACTH secretion. The rate of 3H-NE and 3H-DA accumulation from 3H-tyrosine in vitro was used as an index of catecholamine synthesis rates. Exposure to ether vapor, 30 min of cold environment, or laparotomy increased ACTH secretion significantly, as indicated by plasma corticosterone levels. However, only the ether stress affected hypothalamic catecholamines; both NE and DA synthesis rates were increased in the arcuate nucleus are (ANA), but not in the median eminence (ME) or the residual hypothalamus (RH). Dexamethasone treatment blocked the stress-induced ACTH secretion, but had no affect on basal or stress-induced rates of amine synthesis. It is concluded that catecholamines in the ANA participate in mediating ether stress-induced ACTH secretion.", "contents": "Correlation between hypothalamic catecholamine synthesis and ether stress-induced ACTH secretion. The rates of synthesis of norepinephrine (NE) and dopamine (DA) in several regions of the hypothalamus have been estimated after exposure of rats to stresses that increase ACTH secretion. The rate of 3H-NE and 3H-DA accumulation from 3H-tyrosine in vitro was used as an index of catecholamine synthesis rates. Exposure to ether vapor, 30 min of cold environment, or laparotomy increased ACTH secretion significantly, as indicated by plasma corticosterone levels. However, only the ether stress affected hypothalamic catecholamines; both NE and DA synthesis rates were increased in the arcuate nucleus are (ANA), but not in the median eminence (ME) or the residual hypothalamus (RH). Dexamethasone treatment blocked the stress-induced ACTH secretion, but had no affect on basal or stress-induced rates of amine synthesis. It is concluded that catecholamines in the ANA participate in mediating ether stress-induced ACTH secretion."}
{"id": "PMID:190551", "title": "[Immune humoral response in epilepsy].", "content": "In 68 epileptics in serum immunoglobulin level, antibodies against Kunin CA antigen, S. typhi O and viruses parainfluenzae type I, II and III were determined. The serum IgA leeel (-/x = 106.27, SE = 8.14) was lower than in controls (-/x = = 155.55, SE = 8.12). In 25% of epileptics the IgA level had raised IgG and low IgM levels in the serum. In epileptics the level of antibodies to parainfluenza virus III (-/xg = 71.52) was lower than in the control group (-/xg = 92.29). The investigations gave results which could not answer the question whether disturbances of immune humoral response in epileptics are primary or are due to immunosuppressive action of anticonvulsants.", "contents": "[Immune humoral response in epilepsy]. In 68 epileptics in serum immunoglobulin level, antibodies against Kunin CA antigen, S. typhi O and viruses parainfluenzae type I, II and III were determined. The serum IgA leeel (-/x = 106.27, SE = 8.14) was lower than in controls (-/x = = 155.55, SE = 8.12). In 25% of epileptics the IgA level had raised IgG and low IgM levels in the serum. In epileptics the level of antibodies to parainfluenza virus III (-/xg = 71.52) was lower than in the control group (-/xg = 92.29). The investigations gave results which could not answer the question whether disturbances of immune humoral response in epileptics are primary or are due to immunosuppressive action of anticonvulsants."}
{"id": "PMID:190552", "title": "[Usefulness of a strain of mice with genetically determined audiogenic epilepsy as a model of experimental epilepsy].", "content": "Behavioural and bioelectric characteristics of epileptic seizures caused by acoustic stimulus in mice from the Swiss Albino Rb strain with genetically determined audiogenic epilepsy are presented. The value of this epilepsy model is emphasized stressing that the epileptogenic stimulus acts from a distance, causing no damage to the nervous system and no artifacts. Besides that, seizures can be provoked at a definite frequency and at arbitrarily chosen time. A disadvantage of the model is the necessity of provoking each seizure separately which causes that this model cannot meet one of the conditions of Jasper's definition concerning spontaneity of seizure development. With regard to the course of seizure it is emphasized that it is somewhat similar to human grand mal epilepsy representing the basic phases of seizure. Electrophysiological investigations carried out under conditions of long-term fully reproducible experiment demonstrated presence of very evident and rich electrocorticographic symptomatology of audiogenic epileptic seizure whose behavioural phases show a high correlation with phasic changes in bioelectric brain activity. The investigations carried out in sleep failed to demonstrate differences in the susceptibility to seizure development when the stimulus was applied in waking state or in any of both phases of sleep. This strain is useful to morphological ultrastructural, biochemical and possibly electrophysiological investigations.", "contents": "[Usefulness of a strain of mice with genetically determined audiogenic epilepsy as a model of experimental epilepsy]. Behavioural and bioelectric characteristics of epileptic seizures caused by acoustic stimulus in mice from the Swiss Albino Rb strain with genetically determined audiogenic epilepsy are presented. The value of this epilepsy model is emphasized stressing that the epileptogenic stimulus acts from a distance, causing no damage to the nervous system and no artifacts. Besides that, seizures can be provoked at a definite frequency and at arbitrarily chosen time. A disadvantage of the model is the necessity of provoking each seizure separately which causes that this model cannot meet one of the conditions of Jasper's definition concerning spontaneity of seizure development. With regard to the course of seizure it is emphasized that it is somewhat similar to human grand mal epilepsy representing the basic phases of seizure. Electrophysiological investigations carried out under conditions of long-term fully reproducible experiment demonstrated presence of very evident and rich electrocorticographic symptomatology of audiogenic epileptic seizure whose behavioural phases show a high correlation with phasic changes in bioelectric brain activity. The investigations carried out in sleep failed to demonstrate differences in the susceptibility to seizure development when the stimulus was applied in waking state or in any of both phases of sleep. This strain is useful to morphological ultrastructural, biochemical and possibly electrophysiological investigations."}
{"id": "PMID:190559", "title": "[Glomus tumors in unusual sites].", "content": "Two cases of glomus tumour in unusual sites are described. Their indistinct symptomatology, site and histological polymorphism are made the basis of a general discussion of the histogenesis and possible ongoing pictures of glomus tumours, the classification of which is also felt to be unsatisfactory.", "contents": "[Glomus tumors in unusual sites]. Two cases of glomus tumour in unusual sites are described. Their indistinct symptomatology, site and histological polymorphism are made the basis of a general discussion of the histogenesis and possible ongoing pictures of glomus tumours, the classification of which is also felt to be unsatisfactory."}
{"id": "PMID:190567", "title": "Molar pregnancy of hyperthyroidism.", "content": "A report on a patient with clinical hyperthyroidism associated with hydatidiform mole is presented. Some biochemical characteristics of the thyroid stimulator isolated from the tumour are discussed.", "contents": "Molar pregnancy of hyperthyroidism. A report on a patient with clinical hyperthyroidism associated with hydatidiform mole is presented. Some biochemical characteristics of the thyroid stimulator isolated from the tumour are discussed."}
{"id": "PMID:190571", "title": "The effect of conjugated estrogens on coagulability in menopausal women.", "content": "To investigate the effect of conjugated equine estrogens on the coagulability in menopausal women, blood samples were drawn from 69 menopausal females--35 receiving estrogens and 34 receiving no replacement therapy. Using tests for antithrombin and heparin-antithrombin activities, 14.7% of the control patients were found to be hypercoagulable. This is a 289% increase in the incidence of hypercoagulability in the group treated with estrogens. The particular relevance of this finding to menopausal women and the importance of the use of the coagulation profile in managing such patients is discussed.", "contents": "The effect of conjugated estrogens on coagulability in menopausal women. To investigate the effect of conjugated equine estrogens on the coagulability in menopausal women, blood samples were drawn from 69 menopausal females--35 receiving estrogens and 34 receiving no replacement therapy. Using tests for antithrombin and heparin-antithrombin activities, 14.7% of the control patients were found to be hypercoagulable. This is a 289% increase in the incidence of hypercoagulability in the group treated with estrogens. The particular relevance of this finding to menopausal women and the importance of the use of the coagulation profile in managing such patients is discussed."}
{"id": "PMID:190573", "title": "The value of erythropoietin assay in the follow-up of Wilms' tumor patients.", "content": "Ectopic tumor associated erythropoietin release was measured preoperatively and postoperatively in 36 Wilms' tumor patients followed for an average of three years. Erythropoietin assay results in plasma and urine were related independently to tumor stage as well as to the general clinical judgment following appropriate and exhaustive tests as to whether the disease was active or inactive at the time of the assay. Consistent erythropoietin plasma elevations were correlated with the presence of active disease in all stages of Wilms' tumor. Less consistent elevations were noted in urine specimens concomitantly obtained and assayed. This hormonal assay continues to be of consistent and long-term benefit in predicting or correlating disease recurrence or persistence in Wilms' tumor.", "contents": "The value of erythropoietin assay in the follow-up of Wilms' tumor patients. Ectopic tumor associated erythropoietin release was measured preoperatively and postoperatively in 36 Wilms' tumor patients followed for an average of three years. Erythropoietin assay results in plasma and urine were related independently to tumor stage as well as to the general clinical judgment following appropriate and exhaustive tests as to whether the disease was active or inactive at the time of the assay. Consistent erythropoietin plasma elevations were correlated with the presence of active disease in all stages of Wilms' tumor. Less consistent elevations were noted in urine specimens concomitantly obtained and assayed. This hormonal assay continues to be of consistent and long-term benefit in predicting or correlating disease recurrence or persistence in Wilms' tumor."}
{"id": "PMID:190574", "title": "Male breast cancer: two cases with objective regressions from calusterone (7 alpha, 17 beta-dimethyltestosterone) after failure of orchiectomy.", "content": "Calusterone (7 alpha, 17beta-dimethyltestosterone) is an orally effective weakly androgenic steroid. The antitumor efficacy of calusterone, 200 mg per day against objectively progressing advanced breast cancer in females has already been reported. In the present study calusterone was used in metastatic breast cancer in two male patients. Both had failed to continue respond to orchiectomy and had measurable lesions one in the lungs, the other in the bones. Both patients showed objective regression (blastic response of osteolytic lesions and disappearance of lung metastases) lasting five months in one patients and more than seven months in the other, who is still in regression. Further experience is necessary for statistically adequate results.", "contents": "Male breast cancer: two cases with objective regressions from calusterone (7 alpha, 17 beta-dimethyltestosterone) after failure of orchiectomy. Calusterone (7 alpha, 17beta-dimethyltestosterone) is an orally effective weakly androgenic steroid. The antitumor efficacy of calusterone, 200 mg per day against objectively progressing advanced breast cancer in females has already been reported. In the present study calusterone was used in metastatic breast cancer in two male patients. Both had failed to continue respond to orchiectomy and had measurable lesions one in the lungs, the other in the bones. Both patients showed objective regression (blastic response of osteolytic lesions and disappearance of lung metastases) lasting five months in one patients and more than seven months in the other, who is still in regression. Further experience is necessary for statistically adequate results."}
{"id": "PMID:190575", "title": "Intranuclear inclusion bodies in recurrent aphthous ulcers with a herpetiform pattern.", "content": "Spherical granular and filamentous intranuclear bodies were found in the marginal epithelial cells of recurrent aphthous ulcers with a herpetiform pattern. They ranged from 0.8 to 1.2 mu in size with one to four bodies being present in any one nucleus. Because of their size and the demonstrated lack of DNA or RNA, it was thought that they were not viral in nature, as has been previously reported. It is hypothesized that intranuclear bodies of the type found in this study represent a common manifestation of altered cellular metabolsim produced by several etiologic factors.", "contents": "Intranuclear inclusion bodies in recurrent aphthous ulcers with a herpetiform pattern. Spherical granular and filamentous intranuclear bodies were found in the marginal epithelial cells of recurrent aphthous ulcers with a herpetiform pattern. They ranged from 0.8 to 1.2 mu in size with one to four bodies being present in any one nucleus. Because of their size and the demonstrated lack of DNA or RNA, it was thought that they were not viral in nature, as has been previously reported. It is hypothesized that intranuclear bodies of the type found in this study represent a common manifestation of altered cellular metabolsim produced by several etiologic factors."}
{"id": "PMID:190576", "title": "Mucin-producing cholangiocarcinoma: an autopsy study in Hong Kong.", "content": "Fifty autopsy cases (35 male and 15 female) of mucin-secreting cholangiocarcinoma in Chinese were reviewed. The peak incidence was in the 7th decade for males and in the 6th for females. Massive (37), multinodular (8), diffuse (1) and hilar (4) types were recognized grossly. The hilar tumours arose from the main intrahepatic ducts and the other types originated from smaller ducts. The overall association with stones was 20% and clonorchiasis 92%. Cirrhosis occurred in only 4% of cases. There was an association between the degree of mucin secretion and the presence and severity of clonorchiasis.", "contents": "Mucin-producing cholangiocarcinoma: an autopsy study in Hong Kong. Fifty autopsy cases (35 male and 15 female) of mucin-secreting cholangiocarcinoma in Chinese were reviewed. The peak incidence was in the 7th decade for males and in the 6th for females. Massive (37), multinodular (8), diffuse (1) and hilar (4) types were recognized grossly. The hilar tumours arose from the main intrahepatic ducts and the other types originated from smaller ducts. The overall association with stones was 20% and clonorchiasis 92%. Cirrhosis occurred in only 4% of cases. There was an association between the degree of mucin secretion and the presence and severity of clonorchiasis."}
{"id": "PMID:190581", "title": "Primary Epstein-Barr virus infections in children.", "content": "During a serioepidemiologic survey of a community, 13 (6.2%) of 209 children were found to be experiencing a current or recent primary Epstein-Barr virus (EBV) infection. The sera contained elevated antibody titers to viral capsid antigen of EBV, antibodies to early antigen (EA) of EBV, and specific IgM. The frequency of primary infections was highest in the first decade of life. The primary EBV infections were usually asymptomatic. The antibody to EA was directed predominantly to the R component. A heterophil antibody response was not detected.", "contents": "Primary Epstein-Barr virus infections in children. During a serioepidemiologic survey of a community, 13 (6.2%) of 209 children were found to be experiencing a current or recent primary Epstein-Barr virus (EBV) infection. The sera contained elevated antibody titers to viral capsid antigen of EBV, antibodies to early antigen (EA) of EBV, and specific IgM. The frequency of primary infections was highest in the first decade of life. The primary EBV infections were usually asymptomatic. The antibody to EA was directed predominantly to the R component. A heterophil antibody response was not detected."}
{"id": "PMID:190582", "title": "Antibody-dependent cellular cytotoxicity to target cells infected with herpes simplex viruses: functional adequacy in the neonate.", "content": "The functional adequacy of antibody-dependent cellular cytotoxicity (ADCC) in the human neonate was evaluated in a 51Cr release assay which employs tissue culture cells acutely infected with type 1 or type 2 herpes simplex virus (HSV) as targets. Two aspects of ADCC were assessed: cytotoxic effector activity in cord blood mononuclear cells (MC) and the ability of the antibody mediating ADCC to pass the placenta. Although effector cell activity was readily detected in all 13 cord blood specimens tested, cord blood MC showed moderately reduced cytotoxic activity when compared with blood MC from normal adults at the same effector cell:target cell ratio. This finding suggests that effector cells in cord blood make up a reduced proportion of the total circulating MC population and may be of relevance to the newborn's increased susceptibility to HSV infection. On the other hand, the number of MC in cord blood was found to be almost twice that of adult blood, suggesting that the absolute number of ADCC effector cells in cord blood was within the adult range. The antibody mediating ADCC to HSV-infected cells was shown to be transferred quantitatively across the placenta, providing further evidence that it is an IgG immunoglobulin.", "contents": "Antibody-dependent cellular cytotoxicity to target cells infected with herpes simplex viruses: functional adequacy in the neonate. The functional adequacy of antibody-dependent cellular cytotoxicity (ADCC) in the human neonate was evaluated in a 51Cr release assay which employs tissue culture cells acutely infected with type 1 or type 2 herpes simplex virus (HSV) as targets. Two aspects of ADCC were assessed: cytotoxic effector activity in cord blood mononuclear cells (MC) and the ability of the antibody mediating ADCC to pass the placenta. Although effector cell activity was readily detected in all 13 cord blood specimens tested, cord blood MC showed moderately reduced cytotoxic activity when compared with blood MC from normal adults at the same effector cell:target cell ratio. This finding suggests that effector cells in cord blood make up a reduced proportion of the total circulating MC population and may be of relevance to the newborn's increased susceptibility to HSV infection. On the other hand, the number of MC in cord blood was found to be almost twice that of adult blood, suggesting that the absolute number of ADCC effector cells in cord blood was within the adult range. The antibody mediating ADCC to HSV-infected cells was shown to be transferred quantitatively across the placenta, providing further evidence that it is an IgG immunoglobulin."}
{"id": "PMID:190583", "title": "Protection against varicella in family contacts by immediate inoculation with live varicella vaccine.", "content": "A live varicella vaccine (Oka strain) was given to susceptible household contacts of varicella to test the protective efficacy of the vaccination. Twenty-six contacts of 21 families were vaccinated, usually within three days after onset of the index cases. None of the vaccinated children developed clinical symptoms of varicella. Eighteen of 24 sera obtained before vaccination were found to be seronegative by complement fixation and neutralization tests. Seroconversion was observed in all of the 18. On the other hand, all of 19 unvaccinated contacts in the 15 families, who served as controls, showed typical manifestations of varicella from 10 to 33 days after onset of the index varicella cases. In three families, where only one sibling contact received vaccine and the other was an unvaccinated control, none of the vaccinated children showed any clinical symptoms while unvaccinated controls exhibited typical varicella symptoms 10 to 14 days after the onset of the index cases. These results indicate that varicella is prevented in household contacts by vaccination within three days following exposure.", "contents": "Protection against varicella in family contacts by immediate inoculation with live varicella vaccine. A live varicella vaccine (Oka strain) was given to susceptible household contacts of varicella to test the protective efficacy of the vaccination. Twenty-six contacts of 21 families were vaccinated, usually within three days after onset of the index cases. None of the vaccinated children developed clinical symptoms of varicella. Eighteen of 24 sera obtained before vaccination were found to be seronegative by complement fixation and neutralization tests. Seroconversion was observed in all of the 18. On the other hand, all of 19 unvaccinated contacts in the 15 families, who served as controls, showed typical manifestations of varicella from 10 to 33 days after onset of the index varicella cases. In three families, where only one sibling contact received vaccine and the other was an unvaccinated control, none of the vaccinated children showed any clinical symptoms while unvaccinated controls exhibited typical varicella symptoms 10 to 14 days after the onset of the index cases. These results indicate that varicella is prevented in household contacts by vaccination within three days following exposure."}
{"id": "PMID:190584", "title": "Protective efficacy of vaccination in children in four episodes of natural varicella and zoster in the ward.", "content": "It was previously reported that a live varicella vaccine (Oka strain) has been developed and that the immediate vaccination of hospitalized children was effective for prevention of spread of varicella in a ward. Six to nine months later, there were four separate episodes of varicella and zoster in the same ward. Eighteen children (11 with nephrotic syndrome, 6 with nephritis, and 1  with hepatitis) with no history of varicella were inoculated with a live vaccine before or immediately after admittance or occurence of the varicella and zoster cases. Twelve of them had been receiving steroid therapy and 15 of the 18 were found to be seronegative by complement fixation and neutralization tests before the vaccination. All of them became seropositive after vaccination without any clinical symptoms. The longest period between vaccination and exposure was nine months. None of the vaccinees exhibited varicella symptoms after exposure. Serological follow-up of ten vaccinated children was done, and booster responses were observed in some of them after exposure. These results suggest that the live vaccine affords immunity to the recipients. If hospitalized children are vaccinated before or immediately after exposure, isolation of the patient is unnecessary.", "contents": "Protective efficacy of vaccination in children in four episodes of natural varicella and zoster in the ward. It was previously reported that a live varicella vaccine (Oka strain) has been developed and that the immediate vaccination of hospitalized children was effective for prevention of spread of varicella in a ward. Six to nine months later, there were four separate episodes of varicella and zoster in the same ward. Eighteen children (11 with nephrotic syndrome, 6 with nephritis, and 1  with hepatitis) with no history of varicella were inoculated with a live vaccine before or immediately after admittance or occurence of the varicella and zoster cases. Twelve of them had been receiving steroid therapy and 15 of the 18 were found to be seronegative by complement fixation and neutralization tests before the vaccination. All of them became seropositive after vaccination without any clinical symptoms. The longest period between vaccination and exposure was nine months. None of the vaccinees exhibited varicella symptoms after exposure. Serological follow-up of ten vaccinated children was done, and booster responses were observed in some of them after exposure. These results suggest that the live vaccine affords immunity to the recipients. If hospitalized children are vaccinated before or immediately after exposure, isolation of the patient is unnecessary."}
{"id": "PMID:190585", "title": "Visual masking and carbon monoxide toxicity.", "content": "Thresholds for letters were measured with and without a masking stimulus (presented either to the same eye as the letters or to the other eye) before and after exposure of smokers and nonsmokers to 500 ppm carbon monoxide (CO) in air for 1 hr. Identification of the unmasked letters was not degraded by CO but a number of thresholds of the masked letters were significantly affected among the smokers. The effects of the CO on binocular and interocular masking were similar. These results suggest that the first effects of CO toxicity are neither on the receptors nor central but on the transmission lines in between and that smokers are more susceptible than nonsmokers to short-term increases in the level of CO. The masking phenomenon, however, does not appear to be an unusually sensitive measure of CO toxicity.", "contents": "Visual masking and carbon monoxide toxicity. Thresholds for letters were measured with and without a masking stimulus (presented either to the same eye as the letters or to the other eye) before and after exposure of smokers and nonsmokers to 500 ppm carbon monoxide (CO) in air for 1 hr. Identification of the unmasked letters was not degraded by CO but a number of thresholds of the masked letters were significantly affected among the smokers. The effects of the CO on binocular and interocular masking were similar. These results suggest that the first effects of CO toxicity are neither on the receptors nor central but on the transmission lines in between and that smokers are more susceptible than nonsmokers to short-term increases in the level of CO. The masking phenomenon, however, does not appear to be an unusually sensitive measure of CO toxicity."}
{"id": "PMID:190586", "title": "Necker cube and autokinetic illusions after awakening from REM and NONREM sleep: lack of effect.", "content": "Earlier studies demonstrated differential perceptions of the visual illusions, beta movements and spiral aftereffect, following awakening from REM and NONREM sleep. The present study tested the effects of awakening from the two phases of sleep on two additional visual illusions, the Necker cube and autokinetic illusions. 12 young adults were wakened from REM and NONREM sleep and tested on both illusions for three 1-min. trials, within 1 to 2 min. of the awakening. Comparison of the post-REM and post-NONREM illusions indicated a nonsignificant difference between the two waking conditions in the passive spontaneous reversal rates of the Necker cube. Data for the autokinetic illusion were not reported as they were unreliable.", "contents": "Necker cube and autokinetic illusions after awakening from REM and NONREM sleep: lack of effect. Earlier studies demonstrated differential perceptions of the visual illusions, beta movements and spiral aftereffect, following awakening from REM and NONREM sleep. The present study tested the effects of awakening from the two phases of sleep on two additional visual illusions, the Necker cube and autokinetic illusions. 12 young adults were wakened from REM and NONREM sleep and tested on both illusions for three 1-min. trials, within 1 to 2 min. of the awakening. Comparison of the post-REM and post-NONREM illusions indicated a nonsignificant difference between the two waking conditions in the passive spontaneous reversal rates of the Necker cube. Data for the autokinetic illusion were not reported as they were unreliable."}
{"id": "PMID:190589", "title": "[Enzootic calcinosis and other plant induced calcinoses (author's transl)].", "content": "A review is given of the literature concerning the so-called plant induced calcinosis in animals (tabel I), i.e. diseases which in their patological-anatomical appearance show great similarities with vit. D-intoxication. The etiology of the diseases are discussed in view of the last 5--10 years rapid development of knowledge concerning vit. D3 metabolism. It is pointed out that the most recent results indicate that enzootic calcinosis is caused by a 1,25-dihydrocholecalciferol-glycoside, which is hydrolysed in the intestinal tract. By this reaction 1.25 (OH) 2 cholecalciferol--the biological active metabolite of vit. D3 -- is set free, and thus able to act directly on the intestinal absorption mechanism. By this reaction the point of calcium metabolism regulation is essentially by-passed and calcium and phosphate absorption proceeds essentially out of control, causing hypercalcaemia, hyperphosphataemia, hypersecretion of calcitonin and calcinosis.", "contents": "[Enzootic calcinosis and other plant induced calcinoses (author's transl)]. A review is given of the literature concerning the so-called plant induced calcinosis in animals (tabel I), i.e. diseases which in their patological-anatomical appearance show great similarities with vit. D-intoxication. The etiology of the diseases are discussed in view of the last 5--10 years rapid development of knowledge concerning vit. D3 metabolism. It is pointed out that the most recent results indicate that enzootic calcinosis is caused by a 1,25-dihydrocholecalciferol-glycoside, which is hydrolysed in the intestinal tract. By this reaction 1.25 (OH) 2 cholecalciferol--the biological active metabolite of vit. D3 -- is set free, and thus able to act directly on the intestinal absorption mechanism. By this reaction the point of calcium metabolism regulation is essentially by-passed and calcium and phosphate absorption proceeds essentially out of control, causing hypercalcaemia, hyperphosphataemia, hypersecretion of calcitonin and calcinosis."}
{"id": "PMID:190590", "title": "Sequence analysis of T1 ribonuclease fragments of 18S ribosomal RNA by 5'-terminal labeling, partial digestion, and homochromatography fingerprinting.", "content": "The method employed to determine the sequence of a T1 RNase fragment, A-A-A-A-A-U-A-A-C-A-A-U-A-C-A-Gp, from Novikoff rat hepatoma 18S ribosomal RNA is described. This method is applicable to any oligoribonucleotide produced by specific endonucleases that leave the newly cleaved 5'-end free for labeling with polynucleotide kinase and gamma-(32p)-ATP. The (32p)-labeled oligoribonucleotide is subjected to partial endonucleolytic digestion and fractionated by two-dimensional homochromatography fingerprinting. The nucleotide sequence is determined by following mobility shifts of the labeled and partially digested oligoribonucleotides in homochromatography fingerprinting.", "contents": "Sequence analysis of T1 ribonuclease fragments of 18S ribosomal RNA by 5'-terminal labeling, partial digestion, and homochromatography fingerprinting. The method employed to determine the sequence of a T1 RNase fragment, A-A-A-A-A-U-A-A-C-A-A-U-A-C-A-Gp, from Novikoff rat hepatoma 18S ribosomal RNA is described. This method is applicable to any oligoribonucleotide produced by specific endonucleases that leave the newly cleaved 5'-end free for labeling with polynucleotide kinase and gamma-(32p)-ATP. The (32p)-labeled oligoribonucleotide is subjected to partial endonucleolytic digestion and fractionated by two-dimensional homochromatography fingerprinting. The nucleotide sequence is determined by following mobility shifts of the labeled and partially digested oligoribonucleotides in homochromatography fingerprinting."}
{"id": "PMID:190591", "title": "Arylsulfonyltetrazoles, new coupling reagents and further improvements in the triester method for the synthesis of deoxyribooligonucleotides.", "content": "The modified triester approach has been further improved and refined to the synthesis of defined sequences of deoxyribo-oligonucleotides. Improvements include arylsulfonyltetrazoles as faster and milder condensing agents, benzenesulfonic acid to avoid depurination during deblocking of trityl protecting groups and improved chromatographic procedures for purification of triester intermediates and purification of the final product containing 3'-5' phosphodiester linkages.", "contents": "Arylsulfonyltetrazoles, new coupling reagents and further improvements in the triester method for the synthesis of deoxyribooligonucleotides. The modified triester approach has been further improved and refined to the synthesis of defined sequences of deoxyribo-oligonucleotides. Improvements include arylsulfonyltetrazoles as faster and milder condensing agents, benzenesulfonic acid to avoid depurination during deblocking of trityl protecting groups and improved chromatographic procedures for purification of triester intermediates and purification of the final product containing 3'-5' phosphodiester linkages."}
{"id": "PMID:190592", "title": "Phosphorylation of tRNA by T4 polynucleotide kinase.", "content": "The phosphorylation of various intact tRNA species by T4 polynucleotide kinase has been studied. The apparent Michaelis constant was on the average found to be 100 times lower than for some single-stranded DNAs previously studied. (J.R. Lillehaug and K. Kleppe, (1975) Biochemistry, 14, 1221). Conditions which result in complete phosphorylation of different tRNA species have also been established. Studies on equilibrium constants and the reversibility of the reaction revealed that the phosphorylation reaction is not a true equilibrium reaction under the conditions used in this work.", "contents": "Phosphorylation of tRNA by T4 polynucleotide kinase. The phosphorylation of various intact tRNA species by T4 polynucleotide kinase has been studied. The apparent Michaelis constant was on the average found to be 100 times lower than for some single-stranded DNAs previously studied. (J.R. Lillehaug and K. Kleppe, (1975) Biochemistry, 14, 1221). Conditions which result in complete phosphorylation of different tRNA species have also been established. Studies on equilibrium constants and the reversibility of the reaction revealed that the phosphorylation reaction is not a true equilibrium reaction under the conditions used in this work."}
{"id": "PMID:190593", "title": "Isolation of mammalian tRNAAsp and tRNATyr by lectin-Sepharose affinity column chromatography.", "content": "tRNAAsp from rabbit liver, rat liver and rat ascites hepatoma was readily isolated by concanavalin A-Sepharose (Con A-Sepharose) affinity column chromatography. tRNATyr from these sources was extensively purified by Ricinus communis lectin-Sepharose column chromatography. These results, together with the chromatographic behaviour of four tRNAs (tRNATyr, tRNAHis, tRNAAsn and tRNAAsp) on acetylated DBAE-cellulose column chromatography suggested that tRNAAsp contains a Q nucleoside species having a mannose moiety while tRNATyr contains Q nucleoside with galactose. The sugars attached in 4-position of cyclopentene diol in the Q molecule are therefore not present at random in the four tRNAs, but present only in each specific tRNA. This is the first case which shows that plant agglutinin interacts with nucleic Acid as well as polysaccharide and glycoproteins.", "contents": "Isolation of mammalian tRNAAsp and tRNATyr by lectin-Sepharose affinity column chromatography. tRNAAsp from rabbit liver, rat liver and rat ascites hepatoma was readily isolated by concanavalin A-Sepharose (Con A-Sepharose) affinity column chromatography. tRNATyr from these sources was extensively purified by Ricinus communis lectin-Sepharose column chromatography. These results, together with the chromatographic behaviour of four tRNAs (tRNATyr, tRNAHis, tRNAAsn and tRNAAsp) on acetylated DBAE-cellulose column chromatography suggested that tRNAAsp contains a Q nucleoside species having a mannose moiety while tRNATyr contains Q nucleoside with galactose. The sugars attached in 4-position of cyclopentene diol in the Q molecule are therefore not present at random in the four tRNAs, but present only in each specific tRNA. This is the first case which shows that plant agglutinin interacts with nucleic Acid as well as polysaccharide and glycoproteins."}
{"id": "PMID:190598", "title": "The effects of mercury ingestion on hepatic mitochondrial membranes of chicks.", "content": "Cytochrome c oxidase activity was measured in livers of chicks receiving 0, 200,250 or 300 p.p.m. mercury (as HgC12) in the drinking water beginning at one week of age. In the first experiment treatment with 200 p.p.m. mercury for up to 4 weeks tended to increase the activity of cytochrome c oxidase and decrease the proportion of free (measured in untreated liver preparations) to total (measured in Triton X-100 treated liver preparations) enzyme activity as compared with controls. However, the differences, which appeared after 1 week of treatment were not always statistically significant. The fatty acid composition of mitochondrial lipids was not affected by treatment with 200 p.p.m. mercury for 4 weeks. In the second experiment, treatment with 300 p.p.m. mercury for 4 weeks resulted in significantly higher total cytochrome c oxidase specific activity and a significantly lower proportion of free to total enzyme activity as compared with controls. However, mitochondrial susceptibility to rupture by freezing and thawing was not affected. In the third experiment chicks were given 250 p.p.m. mercury in the drinking water from 1 through 9 weeks of age. The mercury-treated chicks exhibited severe tremors at 9 weeks while the controls were unaffected. Cytochome c oxidase total specific activity was significantly reduced in trembling chicks, and the proportion of free to total enzyme activity was significantly increased as was the susceptibility of isolated mitochondria to rupture by freezing and thawing. The data suggest that moderate levels of mercury administered over an 8 week period can affect adversely the integrity of mitochondrial membranes.", "contents": "The effects of mercury ingestion on hepatic mitochondrial membranes of chicks. Cytochrome c oxidase activity was measured in livers of chicks receiving 0, 200,250 or 300 p.p.m. mercury (as HgC12) in the drinking water beginning at one week of age. In the first experiment treatment with 200 p.p.m. mercury for up to 4 weeks tended to increase the activity of cytochrome c oxidase and decrease the proportion of free (measured in untreated liver preparations) to total (measured in Triton X-100 treated liver preparations) enzyme activity as compared with controls. However, the differences, which appeared after 1 week of treatment were not always statistically significant. The fatty acid composition of mitochondrial lipids was not affected by treatment with 200 p.p.m. mercury for 4 weeks. In the second experiment, treatment with 300 p.p.m. mercury for 4 weeks resulted in significantly higher total cytochrome c oxidase specific activity and a significantly lower proportion of free to total enzyme activity as compared with controls. However, mitochondrial susceptibility to rupture by freezing and thawing was not affected. In the third experiment chicks were given 250 p.p.m. mercury in the drinking water from 1 through 9 weeks of age. The mercury-treated chicks exhibited severe tremors at 9 weeks while the controls were unaffected. Cytochome c oxidase total specific activity was significantly reduced in trembling chicks, and the proportion of free to total enzyme activity was significantly increased as was the susceptibility of isolated mitochondria to rupture by freezing and thawing. The data suggest that moderate levels of mercury administered over an 8 week period can affect adversely the integrity of mitochondrial membranes."}
{"id": "PMID:190594", "title": "Validation of questionnaires on physical function.", "content": "Data-gathering instruments were used in a randomized controlled trial, designed to assess a structured preoperative educational program for elective surgical patients. The key dependent variable was the physical functional capacity of patients following surgery. Questionnaires were developed to measure physical functioning in the immediate postoperative period, after discharge from hospital, and 10 days and 33 days after surgery. Statistical techniques used to measure interobserver agreement and bias  were worker's chi square, Cicchett's statistic, the contingency coefficient, Kendall's Taub, and Kendall's coefficient of concordance W. The standardized questionnaires permitted classification of patients's postoperative physical functions with results that agreed highly with the classification done by experienced clinicians who cared for the same patients.", "contents": "Validation of questionnaires on physical function. Data-gathering instruments were used in a randomized controlled trial, designed to assess a structured preoperative educational program for elective surgical patients. The key dependent variable was the physical functional capacity of patients following surgery. Questionnaires were developed to measure physical functioning in the immediate postoperative period, after discharge from hospital, and 10 days and 33 days after surgery. Statistical techniques used to measure interobserver agreement and bias  were worker's chi square, Cicchett's statistic, the contingency coefficient, Kendall's Taub, and Kendall's coefficient of concordance W. The standardized questionnaires permitted classification of patients's postoperative physical functions with results that agreed highly with the classification done by experienced clinicians who cared for the same patients."}
{"id": "PMID:190599", "title": "Effect of formaldehyde on disinfection of filtered air under positive pressure (FAPP) type house.", "content": "Effect of formaldehyde liberated from formalin on disinfection of the surface of a filtered air under positive pressure (FAPP) house and the surface of equipment placed in the house was studied. Escherichia coli, Staphylococcus aureus and avian adenovirus were used in this study as a indicator to evaluate degree of disinfection. Satisfactory degree of disinfection of the house and equipment was obtained when formaldehyde was liberated from 40 ml. of formalin per 1 m.3 capacity. Bacteria and virus used in the experiments, as well as air-borne organisms in the house, were perfectly inactivated by fumigation for 24 hours at the level of formalin mentioned above.", "contents": "Effect of formaldehyde on disinfection of filtered air under positive pressure (FAPP) type house. Effect of formaldehyde liberated from formalin on disinfection of the surface of a filtered air under positive pressure (FAPP) house and the surface of equipment placed in the house was studied. Escherichia coli, Staphylococcus aureus and avian adenovirus were used in this study as a indicator to evaluate degree of disinfection. Satisfactory degree of disinfection of the house and equipment was obtained when formaldehyde was liberated from 40 ml. of formalin per 1 m.3 capacity. Bacteria and virus used in the experiments, as well as air-borne organisms in the house, were perfectly inactivated by fumigation for 24 hours at the level of formalin mentioned above."}
{"id": "PMID:190600", "title": "Effect of ultraviolet light and oral vitamin D3 on rachitic chicks fed diets containing either corn or rye.", "content": "Three experiments using day-old chicks were conducted in battery brooders to further study the rye-vitamin D antagonism. Birds were fed a vitamin D3-free diet containing corn or rye and submitted to diverse treatments for the first 10 days. At this time the chicks were either continued on the same diet or changed to other grain-type diets. The effect of ultraviolet light exposure on the chicks and of a single oral dose of vitamin D3 was studied, and body weight gain and bone ash were determined after a one-week experimental period. Rachitic chicks on a corn diet responded significantly better than rye-fed chicks to a single oral dose of vitamin D3, based on bone ash of fat-free, dry tibia. This rachitogenic effect of rye was completely overcome by exposing the chicks to ultraviolet light or by water extraction or acid-autoclaving this grain. The results also demonstrate that the interference by rye does not persist after this grain is removed from the diet.", "contents": "Effect of ultraviolet light and oral vitamin D3 on rachitic chicks fed diets containing either corn or rye. Three experiments using day-old chicks were conducted in battery brooders to further study the rye-vitamin D antagonism. Birds were fed a vitamin D3-free diet containing corn or rye and submitted to diverse treatments for the first 10 days. At this time the chicks were either continued on the same diet or changed to other grain-type diets. The effect of ultraviolet light exposure on the chicks and of a single oral dose of vitamin D3 was studied, and body weight gain and bone ash were determined after a one-week experimental period. Rachitic chicks on a corn diet responded significantly better than rye-fed chicks to a single oral dose of vitamin D3, based on bone ash of fat-free, dry tibia. This rachitogenic effect of rye was completely overcome by exposing the chicks to ultraviolet light or by water extraction or acid-autoclaving this grain. The results also demonstrate that the interference by rye does not persist after this grain is removed from the diet."}
{"id": "PMID:190601", "title": "[Histochemical characteristics of the activity of succinate dehydrogenase and cytochrome oxidase in certain tissues and organs of patients with thyrotoxicosis and animals with experimental thyroidin toxicosis].", "content": "The activity of succinic dehydrogenase and cytochromoxidase was studied histochemically in the peripheral blood leukocytes, the thyroid gland tissue and the skeletal muscles of the patients suffering from thyrotoxicosis. The activity of these enzymes is also determined in the blood leukocytes, the cardiac muscle, the liver and the skeletal muscles of the experimental animals given thyroidin in a dose of 0.1 g per 100 g of body weight in the course of 10 days. A marked elevation of the activity of the oxidative enzymes in the patients with an increase of the severity of thyrotoxicosis and in the animals after the thyroidin administration was noted. The absence of any changes in the succinic dehydrogenase and cytochromoxidase activity in the tissue of the skeletal muscles permitted to suppose that increase of the oxidative processes occurred primarily in the organs bearing a great functional load (the thyroid gland, liver, skeletal muscle, etc.).", "contents": "[Histochemical characteristics of the activity of succinate dehydrogenase and cytochrome oxidase in certain tissues and organs of patients with thyrotoxicosis and animals with experimental thyroidin toxicosis]. The activity of succinic dehydrogenase and cytochromoxidase was studied histochemically in the peripheral blood leukocytes, the thyroid gland tissue and the skeletal muscles of the patients suffering from thyrotoxicosis. The activity of these enzymes is also determined in the blood leukocytes, the cardiac muscle, the liver and the skeletal muscles of the experimental animals given thyroidin in a dose of 0.1 g per 100 g of body weight in the course of 10 days. A marked elevation of the activity of the oxidative enzymes in the patients with an increase of the severity of thyrotoxicosis and in the animals after the thyroidin administration was noted. The absence of any changes in the succinic dehydrogenase and cytochromoxidase activity in the tissue of the skeletal muscles permitted to suppose that increase of the oxidative processes occurred primarily in the organs bearing a great functional load (the thyroid gland, liver, skeletal muscle, etc.)."}
{"id": "PMID:190603", "title": "[Certain indicators of carbohydrate metabolism and functional state of the islands of Langerhans in thyrotoxicosis].", "content": "The character of the sugar curves, blood insulin activity and the activity of glucose-6-phosphatase was studied in patients with thyrotoxicosis. It was revealed that thyrotoxicosis was accompanied by an increase in Bodwen's hyperglycemic coefficient with the normal values of Rafalsky's and Sokolnikov's coefficients. In this disease blood insulin activity was elevated, and the response of the insular apparatus to hyperglycemia considerably exceeded such in the control. The blood serum activity of glucoso-6-phosphatase was also elevated and failed to change in different glycemia levels. The mentioned indices increased considerably with the aggravation of the disease.", "contents": "[Certain indicators of carbohydrate metabolism and functional state of the islands of Langerhans in thyrotoxicosis]. The character of the sugar curves, blood insulin activity and the activity of glucose-6-phosphatase was studied in patients with thyrotoxicosis. It was revealed that thyrotoxicosis was accompanied by an increase in Bodwen's hyperglycemic coefficient with the normal values of Rafalsky's and Sokolnikov's coefficients. In this disease blood insulin activity was elevated, and the response of the insular apparatus to hyperglycemia considerably exceeded such in the control. The blood serum activity of glucoso-6-phosphatase was also elevated and failed to change in different glycemia levels. The mentioned indices increased considerably with the aggravation of the disease."}
{"id": "PMID:190607", "title": "Effect of gemfibrozil on lipoprotein concentrations in different types of hyperlipoproteinaemia.", "content": "The lipoprotein lowering effect of gemfibrozil, 400 mg twice daily, was studied for 24 weeks in 26 subjects with primary hyperlipoproteinaemia (type IIa, 5; IIb, 3; III, 3; and IV, 15). Maximum effects were noted after four weeks on very low density lipoproteins (VLDL) and after 12 weeks on low density lipoproteins (LDL), these effects remaining throughout the study. Gemfibrozil decreased VLDL triglycerides (TG) in all types of hyperlipoproteinaemia according to the equation: deltaVLDL TG (mmol/l) = -0.80 X initial VLDL TG concentration + 0.68 The drug affected the low density lipoprotein (LDL) cholesterol= -0.45 X initial LDL cholesterol + 61 This means that LDL cholesterol on average decreased if the initial LDL concentration was above 135 mg/100 ml and increased below that concentration. LDL TG and high density lipoprotein (HDL) TG concentrations also decreased significantly. A slight increase in HDL cholesterol concentration occurred after administration of gemfibrozil. Two subjects had to stop treatment because of nausea and abdominal pain respectively, attributed to the drug. No biochemical side effects were noted.", "contents": "Effect of gemfibrozil on lipoprotein concentrations in different types of hyperlipoproteinaemia. The lipoprotein lowering effect of gemfibrozil, 400 mg twice daily, was studied for 24 weeks in 26 subjects with primary hyperlipoproteinaemia (type IIa, 5; IIb, 3; III, 3; and IV, 15). Maximum effects were noted after four weeks on very low density lipoproteins (VLDL) and after 12 weeks on low density lipoproteins (LDL), these effects remaining throughout the study. Gemfibrozil decreased VLDL triglycerides (TG) in all types of hyperlipoproteinaemia according to the equation: deltaVLDL TG (mmol/l) = -0.80 X initial VLDL TG concentration + 0.68 The drug affected the low density lipoprotein (LDL) cholesterol= -0.45 X initial LDL cholesterol + 61 This means that LDL cholesterol on average decreased if the initial LDL concentration was above 135 mg/100 ml and increased below that concentration. LDL TG and high density lipoprotein (HDL) TG concentrations also decreased significantly. A slight increase in HDL cholesterol concentration occurred after administration of gemfibrozil. Two subjects had to stop treatment because of nausea and abdominal pain respectively, attributed to the drug. No biochemical side effects were noted."}
{"id": "PMID:190604", "title": "[Histochemical characteristics of some oxidation-reduction hydrolytic enzymes in different forms of goiter].", "content": "Histochemical study of some enzymatic systems was conducted in various form of goiter. A study was made of the thyroid gland tissue obtained during the operation in 96 patients. Euthyrosis was accompanied by a decrease in the succinic dehydrogenase, cytochromoxidase, iodide peroxidase, acid and alkaline phosphatase activity. As to thyrotoxic goiter - it displayed an increase in the activity of these enzymes and desquamation of the follicular epithelium; the rejected cells possessed a high acid phosphatase activity. In comparison with thyrotoxic goiter, Askinazi's cell count was increased in the euthyroid macrofollicular nodular and diffuse goiter.", "contents": "[Histochemical characteristics of some oxidation-reduction hydrolytic enzymes in different forms of goiter]. Histochemical study of some enzymatic systems was conducted in various form of goiter. A study was made of the thyroid gland tissue obtained during the operation in 96 patients. Euthyrosis was accompanied by a decrease in the succinic dehydrogenase, cytochromoxidase, iodide peroxidase, acid and alkaline phosphatase activity. As to thyrotoxic goiter - it displayed an increase in the activity of these enzymes and desquamation of the follicular epithelium; the rejected cells possessed a high acid phosphatase activity. In comparison with thyrotoxic goiter, Askinazi's cell count was increased in the euthyroid macrofollicular nodular and diffuse goiter."}
{"id": "PMID:190608", "title": "Gemfibrozil: effect on serum lipids, lipoproteins, postheparin plasma lipase activities and glucose tolerance in primary hypertriglyceridaemia.", "content": "The hypolipidaemic effect of a new drug, gemfibrozil (CI-719), was studied for 20 weeks in 20 patients with primary type IIb, III, IV or V hyperlipoproteinaemia. Baseline recordings of serum cholesterol (9.1 mmol/l), triglyceride (3.79 mmol/l) and ultra-centrifugally isolated lipoproteins were obtained during a six-week pretreatment period with stable diet and body weight. With 800 mg of gemfibrozil per day given in two divided doses, the mean serum triglyceride and cholesterol levels were decreased by 44.6% and 10.5% respectively, during 20 treatment weeks. Only 2 patients were completely resistant to the hypolipidaemic action of the drug. Serum triglyceride was brought down to normal levels in 9 subjects. After 12 weeks of treatment the mean VLDL-triglyceride, VLDL-cholesterol, and LDL-triglyceride were reduced by 48.5%, 57.6%, and 22.7% respectively, while the HDL-cholesterol rose by 16%. The LDL-cholesterol increased slightly but significantly during treatment in type IV patients and decreased in type IIb patients. The change of LDL-cholesterol showed an inverse correlation with the initial LDL-cholesterol level (r=-0.87). The postheparin plasma lipoprotein lipase and hepatic lipase activities, determined separately by an immunochemical method, increased during four weeks of gemfibrozil treatment (+18.1% and +20.6% respectively), but neither of these changes was significantly correlated with the changes in any of the serum lipid or lipoprotein levels. Oral glucose tolerance was not influenced by the treatment, but one-hour plasma insulin increased slightly during administration of the drug. One patient discontinued the drug after eight weeks because of generalized allergic eczema, but no other side effects were recorded. It is concluded that gemfibrozil is highly effective in reducing elevated serum VLDL levels. The simultaneous elevation of LDL in type IV patients needs more attention and study. The mechanism of the hypolipidaemic action of the drug is so far obscure, but it might partly be due to an increased efficiency in VLDL removal by an increased activity of lipoprotein lipase.", "contents": "Gemfibrozil: effect on serum lipids, lipoproteins, postheparin plasma lipase activities and glucose tolerance in primary hypertriglyceridaemia. The hypolipidaemic effect of a new drug, gemfibrozil (CI-719), was studied for 20 weeks in 20 patients with primary type IIb, III, IV or V hyperlipoproteinaemia. Baseline recordings of serum cholesterol (9.1 mmol/l), triglyceride (3.79 mmol/l) and ultra-centrifugally isolated lipoproteins were obtained during a six-week pretreatment period with stable diet and body weight. With 800 mg of gemfibrozil per day given in two divided doses, the mean serum triglyceride and cholesterol levels were decreased by 44.6% and 10.5% respectively, during 20 treatment weeks. Only 2 patients were completely resistant to the hypolipidaemic action of the drug. Serum triglyceride was brought down to normal levels in 9 subjects. After 12 weeks of treatment the mean VLDL-triglyceride, VLDL-cholesterol, and LDL-triglyceride were reduced by 48.5%, 57.6%, and 22.7% respectively, while the HDL-cholesterol rose by 16%. The LDL-cholesterol increased slightly but significantly during treatment in type IV patients and decreased in type IIb patients. The change of LDL-cholesterol showed an inverse correlation with the initial LDL-cholesterol level (r=-0.87). The postheparin plasma lipoprotein lipase and hepatic lipase activities, determined separately by an immunochemical method, increased during four weeks of gemfibrozil treatment (+18.1% and +20.6% respectively), but neither of these changes was significantly correlated with the changes in any of the serum lipid or lipoprotein levels. Oral glucose tolerance was not influenced by the treatment, but one-hour plasma insulin increased slightly during administration of the drug. One patient discontinued the drug after eight weeks because of generalized allergic eczema, but no other side effects were recorded. It is concluded that gemfibrozil is highly effective in reducing elevated serum VLDL levels. The simultaneous elevation of LDL in type IV patients needs more attention and study. The mechanism of the hypolipidaemic action of the drug is so far obscure, but it might partly be due to an increased efficiency in VLDL removal by an increased activity of lipoprotein lipase."}
{"id": "PMID:190605", "title": "[Effect of ACTH on the transformation of progesterone by the adrenal glands of human fetuses in vitro].", "content": "It was shown in vitro that ACTH influenced the progesterone transformation increasing corticosterone production only in those fetuses whose adrenal glands, in the absence of ACTH, transformed progesterone chiefly into hydrocortisone (8--12-week fetuses). But exogenous ACTH failed to influence such transformation of progesterone in 17--24-week fetuses in which the adrenal glands, in the absence of ACTH preparation, produced an equal amount of hydrocortisone and corticosterone. The results obtained and also the data on ACTH content in the hypophysis and the blood of human fetuses at various periods of prenatal development indicated that the changes in progesterone transformation occurring with the advance of fetal age was caused by endogenous ACTH.", "contents": "[Effect of ACTH on the transformation of progesterone by the adrenal glands of human fetuses in vitro]. It was shown in vitro that ACTH influenced the progesterone transformation increasing corticosterone production only in those fetuses whose adrenal glands, in the absence of ACTH, transformed progesterone chiefly into hydrocortisone (8--12-week fetuses). But exogenous ACTH failed to influence such transformation of progesterone in 17--24-week fetuses in which the adrenal glands, in the absence of ACTH preparation, produced an equal amount of hydrocortisone and corticosterone. The results obtained and also the data on ACTH content in the hypophysis and the blood of human fetuses at various periods of prenatal development indicated that the changes in progesterone transformation occurring with the advance of fetal age was caused by endogenous ACTH."}
{"id": "PMID:190609", "title": "Gemfibrozil treatment: a comparison with clofibrate.", "content": "Gemfibrozil was found to be an effective hypotriglyceridaemic agent in types IV, IIb and V hyperlipoproteinaemia. When given at a dose level of 800 mg/day its activity was nearly of the same order of magnitude as 1.5 g/day of clofibrate.", "contents": "Gemfibrozil treatment: a comparison with clofibrate. Gemfibrozil was found to be an effective hypotriglyceridaemic agent in types IV, IIb and V hyperlipoproteinaemia. When given at a dose level of 800 mg/day its activity was nearly of the same order of magnitude as 1.5 g/day of clofibrate."}
{"id": "PMID:190610", "title": "Lipokinetic studies with gemfibrozil (CI-719).", "content": "Gemfibrozil (CI-719) has proved to be an effective agent in reducing the plasma triglyceride levels in experimental animals and in patients with endogenous hypertriglyceridaemia. We have confirmed these findings.", "contents": "Lipokinetic studies with gemfibrozil (CI-719). Gemfibrozil (CI-719) has proved to be an effective agent in reducing the plasma triglyceride levels in experimental animals and in patients with endogenous hypertriglyceridaemia. We have confirmed these findings."}
{"id": "PMID:190619", "title": "Facilitation of retention performance in mice by posttraining diethyldithiocarbamate.", "content": "These experiments examined the effects in mice of posttraining injections of diethyldithiocarbamate (DDC) upon retention (7 days after training) of active avoidance learning and upon whole brain catecholamine levels. When administered immediately following training, DDC enhanced retention performance. The degree of enhancement varied directly with dose. DDC did not significantly affect retention performance if the injections were delayed 1 or 4 hours after training. Also, DDC administered 30 min prior to training did not affect retention performance. DDC (900 mg/kg) produced a large but transient increase in whole brain dopamine (DA) levels while norepinephrine (NE) levels were lowered.", "contents": "Facilitation of retention performance in mice by posttraining diethyldithiocarbamate. These experiments examined the effects in mice of posttraining injections of diethyldithiocarbamate (DDC) upon retention (7 days after training) of active avoidance learning and upon whole brain catecholamine levels. When administered immediately following training, DDC enhanced retention performance. The degree of enhancement varied directly with dose. DDC did not significantly affect retention performance if the injections were delayed 1 or 4 hours after training. Also, DDC administered 30 min prior to training did not affect retention performance. DDC (900 mg/kg) produced a large but transient increase in whole brain dopamine (DA) levels while norepinephrine (NE) levels were lowered."}
{"id": "PMID:190620", "title": "Effect of ACTH 4-10 on copulatory bahavior and on the response for socio-sexual motivation in the female rat.", "content": "Female copulatory behavior and the urge of a female rat to seek contact with a sexually active male was studied after treatment with the peptide ACTH 4-10. No effects of this peptide were seen on the copulatory response of ovariectomized females treated with estradiol benzoate (EB) alone or EB and progesterone combined. An increasing barrier technique was used to measure how much of an average stimulus (cresssing an electrified grid) a female was willing to endure to gain contact with sexually active male. It has been shown in previous investigations (15) with ovariectomized rats that after a certain time of adaptation and training in this apparatus the response attained remains at a certain basal level from which it is increased by treatment with EB. Animals treated with ACTH 4-10 during the phase of adaptation and training attained a significantly higher basal response level than controls. This effect was only observed when the peptide treatment covered the period of adaptation and was not seen when the treatment was started after this critical period. The EB-induced response was not influenced by ACTH 4-10 given during the period of adaptation or given in connection with the EB treatment. It is concluded that ACTH 4-10 influenced the acquired response level but had no effect on steroid induced responses, which are probably controlled by more innate mechanisms.", "contents": "Effect of ACTH 4-10 on copulatory bahavior and on the response for socio-sexual motivation in the female rat. Female copulatory behavior and the urge of a female rat to seek contact with a sexually active male was studied after treatment with the peptide ACTH 4-10. No effects of this peptide were seen on the copulatory response of ovariectomized females treated with estradiol benzoate (EB) alone or EB and progesterone combined. An increasing barrier technique was used to measure how much of an average stimulus (cresssing an electrified grid) a female was willing to endure to gain contact with sexually active male. It has been shown in previous investigations (15) with ovariectomized rats that after a certain time of adaptation and training in this apparatus the response attained remains at a certain basal level from which it is increased by treatment with EB. Animals treated with ACTH 4-10 during the phase of adaptation and training attained a significantly higher basal response level than controls. This effect was only observed when the peptide treatment covered the period of adaptation and was not seen when the treatment was started after this critical period. The EB-induced response was not influenced by ACTH 4-10 given during the period of adaptation or given in connection with the EB treatment. It is concluded that ACTH 4-10 influenced the acquired response level but had no effect on steroid induced responses, which are probably controlled by more innate mechanisms."}
{"id": "PMID:190622", "title": "Effect of epinephrine on cyclic AMP levels and adenylate cyclase and phosphodiesterase activities in control and antigen-sensitized guinea pig lungs.", "content": "Cyclic AMP levels and adenylate cyclase and phosphodiesterase activities were measured in control and ovalbumin-sensitized guinea pig lungs. Cyclic AMP levels were raised by epinephrine (0.01-10 mug/ml) in both control and sensitized lungs; the response being larger in the former group. Epinephrine (10(-9) -10(-6) M) stimulated adenylate cyclase in sensitized but had only a minimal effect in control preparations. Phosphodiesterase activities were equal in both groups. The hypersensitivity of adenylate cyclase response to epinephrine concurrent with diminished accumulation of cyclic AMP in sensitized guinea pigs indicate that antigen sensitization alters the response of the cyclic AMP system to epinephrine.", "contents": "Effect of epinephrine on cyclic AMP levels and adenylate cyclase and phosphodiesterase activities in control and antigen-sensitized guinea pig lungs. Cyclic AMP levels and adenylate cyclase and phosphodiesterase activities were measured in control and ovalbumin-sensitized guinea pig lungs. Cyclic AMP levels were raised by epinephrine (0.01-10 mug/ml) in both control and sensitized lungs; the response being larger in the former group. Epinephrine (10(-9) -10(-6) M) stimulated adenylate cyclase in sensitized but had only a minimal effect in control preparations. Phosphodiesterase activities were equal in both groups. The hypersensitivity of adenylate cyclase response to epinephrine concurrent with diminished accumulation of cyclic AMP in sensitized guinea pigs indicate that antigen sensitization alters the response of the cyclic AMP system to epinephrine."}
{"id": "PMID:190623", "title": "Characterization of the oxybutynin antagonism of drug-induced spasms in detrusor.", "content": "Oxybutynin chloride exerts a moderate anticholinergic effect on rabbit detrusor in vitro, which is reversible and competitive in nature (KB = 4.7 x 10(-9), and midway in potency between atropine and papaverine. In addition, oxybutynin strongly antagonizes BaCl2-induced spasms of detrusor with a potency equivalent to that of papaverine and 10 times that of atropine. This musculotropic spasmolytic effect is slightly greater in rabbit than human or monkey tissue, and noncompetitive (pD2 = 5.5). This direct relaxant effect, unlike that of papaverine, is not mediated by the inhibition of tissue phosphodiesterase, but probably reflects oxybutynin's local anesthetic properties and associated effects on Ca++ fluxes and binding.", "contents": "Characterization of the oxybutynin antagonism of drug-induced spasms in detrusor. Oxybutynin chloride exerts a moderate anticholinergic effect on rabbit detrusor in vitro, which is reversible and competitive in nature (KB = 4.7 x 10(-9), and midway in potency between atropine and papaverine. In addition, oxybutynin strongly antagonizes BaCl2-induced spasms of detrusor with a potency equivalent to that of papaverine and 10 times that of atropine. This musculotropic spasmolytic effect is slightly greater in rabbit than human or monkey tissue, and noncompetitive (pD2 = 5.5). This direct relaxant effect, unlike that of papaverine, is not mediated by the inhibition of tissue phosphodiesterase, but probably reflects oxybutynin's local anesthetic properties and associated effects on Ca++ fluxes and binding."}
{"id": "PMID:190624", "title": "Experimental considerations biological ESR studies. II. Chromium-tissue complexes detected by electron spin resonance.", "content": "The nature and origin of a g = 1-98 signal observed in ESR investigations of tissue have been established. It is due to paramagnetic chromium which is introduced into tissues during sample handling. This characteristic signal could be used to measure chromium levels in tissues.", "contents": "Experimental considerations biological ESR studies. II. Chromium-tissue complexes detected by electron spin resonance. The nature and origin of a g = 1-98 signal observed in ESR investigations of tissue have been established. It is due to paramagnetic chromium which is introduced into tissues during sample handling. This characteristic signal could be used to measure chromium levels in tissues."}
{"id": "PMID:190627", "title": "[Electroneurographical examination of agricultural workers exposed to plant protective agents].", "content": "Clinical and neurological as well as electromyographic examinations were made on twenty-five subjects working in agriculture and handling plant protection products. Measurements of the rate of nerve conduction were made on the peroneal and median nerves. The average rate of conduction of the peroneal nerve was found to be reduced in persons who had been exposed o plant protectives for more than three years. Electroneurography appears to be useful method of recognizing polyneuropathic symptoms of chronic and toxic affections caused by insecticides.", "contents": "[Electroneurographical examination of agricultural workers exposed to plant protective agents]. Clinical and neurological as well as electromyographic examinations were made on twenty-five subjects working in agriculture and handling plant protection products. Measurements of the rate of nerve conduction were made on the peroneal and median nerves. The average rate of conduction of the peroneal nerve was found to be reduced in persons who had been exposed o plant protectives for more than three years. Electroneurography appears to be useful method of recognizing polyneuropathic symptoms of chronic and toxic affections caused by insecticides."}
{"id": "PMID:190628", "title": "On dreaming at sleep onset.", "content": "The position that dreaming occurs exclusively during REM sleep, which has its first onset after sixty to ninety minutes of nonREM sleep, has been effectively refuted in sleep laboratories but remains uncorrected in the psychoanalytic literature. Examples of hallucinatory activity occurring during the sleep onset period and during a brief nap are shown to have all the characteristics of dreams, including latent content related to repressed material from childhood.", "contents": "On dreaming at sleep onset. The position that dreaming occurs exclusively during REM sleep, which has its first onset after sixty to ninety minutes of nonREM sleep, has been effectively refuted in sleep laboratories but remains uncorrected in the psychoanalytic literature. Examples of hallucinatory activity occurring during the sleep onset period and during a brief nap are shown to have all the characteristics of dreams, including latent content related to repressed material from childhood."}
{"id": "PMID:190629", "title": "Cocaine effects on sleep parameters in the rat.", "content": "Cocaine in 6 mg/kg doses was administered orally and intraperitoneally to rats and sleep EEG's recorded. Cocaine significantly reduced total sleep time, slow-wave sleep, and sleep latency. Rapid eye movement sleep (REM) was significantly suppressed during the first half of the sleep recording. These effects were evident by both routes of administration. The effects of cocaine on total sleep time in animals parallels that observed in man.", "contents": "Cocaine effects on sleep parameters in the rat. Cocaine in 6 mg/kg doses was administered orally and intraperitoneally to rats and sleep EEG's recorded. Cocaine significantly reduced total sleep time, slow-wave sleep, and sleep latency. Rapid eye movement sleep (REM) was significantly suppressed during the first half of the sleep recording. These effects were evident by both routes of administration. The effects of cocaine on total sleep time in animals parallels that observed in man."}
{"id": "PMID:190630", "title": "The effect of labour on uterine blood flow in the pregnant ewe.", "content": "The effect of labour on cardiac output and uterine blood flow was measured in pregnant ewes at a mean gestation of 124 days using radioactive microspheres labelled with 169Yb and 85Sr. Labour was induced by a continuous infusion of ACTH into the foetal circulation. Cardiac ouput measured before ACTH infusion in seven ewes was 5234 +/- 175-9 ml./min (mean +/- S.E.) and total uterine blood flow was 732 +/- 57-9 ml./min (mean +/- S.E.). Measurements during labour in six ewes showed a significant increase in cardiac output to 6175 +/- 149-6 ml./min (P less than 0-005) but no significant change in uterine blood flow. However, the partition of blood flow was altered; thus myometrial flow increased by 67% from 114 +/- 15-4 ml./min to 190 +/- 13-2 ml./min (P less than 0-005) while placental blood flow decreased, although not significantly, from 618 +/- 55-9 ml./min to 575 +/- 40-7 ml./min. Similar changes were observed in one ewe in spontaneous labour at term and in another ewe receiving an infusion of 4 mg oestradiol 17beta over a 24 hr period. It is concluded that labour is not associated with any major alternation in total uterine blood flow although myometrial blood flow is increased. It is not known whether this is due to the rise in circulating oestrogens which occurs prior to parturition in the ewe, or to other factors such as the work of uterine muscle during labour.", "contents": "The effect of labour on uterine blood flow in the pregnant ewe. The effect of labour on cardiac output and uterine blood flow was measured in pregnant ewes at a mean gestation of 124 days using radioactive microspheres labelled with 169Yb and 85Sr. Labour was induced by a continuous infusion of ACTH into the foetal circulation. Cardiac ouput measured before ACTH infusion in seven ewes was 5234 +/- 175-9 ml./min (mean +/- S.E.) and total uterine blood flow was 732 +/- 57-9 ml./min (mean +/- S.E.). Measurements during labour in six ewes showed a significant increase in cardiac output to 6175 +/- 149-6 ml./min (P less than 0-005) but no significant change in uterine blood flow. However, the partition of blood flow was altered; thus myometrial flow increased by 67% from 114 +/- 15-4 ml./min to 190 +/- 13-2 ml./min (P less than 0-005) while placental blood flow decreased, although not significantly, from 618 +/- 55-9 ml./min to 575 +/- 40-7 ml./min. Similar changes were observed in one ewe in spontaneous labour at term and in another ewe receiving an infusion of 4 mg oestradiol 17beta over a 24 hr period. It is concluded that labour is not associated with any major alternation in total uterine blood flow although myometrial blood flow is increased. It is not known whether this is due to the rise in circulating oestrogens which occurs prior to parturition in the ewe, or to other factors such as the work of uterine muscle during labour."}
{"id": "PMID:190633", "title": "[The diagnostic value of the determination of cyclic 3',5'-adenosine monophosphate (cAMP) in urine].", "content": "Many hormones initiate their biologic actions by augmenting the intracellular concentrations of 3',5'-adenosine monophosphate (cyclic AMP). The nucleotide has been found in body fluids; its determination in plasma and urine can be performed by a rapid, simple and specific method: the cyclic AMP assay kit of the Radiochemical Centre (Amersham, England). The assay is based on the competition between unlabelled cAMP and a fixed quantity of the tritium labelled compound for binding to a bovine muscle protein which has a high specificity and affinity for cAMP. Different factors must be considered in evaluating the 24 h urinary content of the nucleotide: the renal or extrarenal origin of cAMP and the functional status of the kidneys. In basal conditions the urinary cAMP excretion is significantly correlated with creatinine excretion (n = 67; r = 0.47; p less than 0.001) thus confirming that the most part of cAMP excreted is derived from the plasma by glomerular filtration. Parathyroid hormone (PTH) stimulates adenylate cyclase predominantly in the renal cortex, whereas vasopressin (ADH) stimulated the enzyme in the medulla; thus PTH and ADH could increase the amount of cAMP in the urine from the renal source. In a case of diabetes insipidus and infusion of ADH caused a prompt rise in cAMP urinary excretion. In 5 normals an infusion of bovine synthetic parathyroid hormone caused an increased excretion of cAMP that preceded the phosphaturic response. An infusion of salmon synthetic calcitonin caused a rise in phosphate excretion and no increase in cAMP urinary content. As it concerns the two calciotopic hormones, PTH and CT, it is reasonable to assume that renal receptors are distinct. The 24 h urinary excretion of cAMP in 55 control subjects (3613 +/- 1460 D.S. n moles) was contrasted with the lower excretion in 25 elderly subjects (70-93 years: 1804 +/- 699 n moles), with the high cAMP excretion in a patient with hyperparathyroidism (that fell to normal values following removal of the parathyroid adenoma) and with the low cAMP excretion in patients with primary or surgical hypoparathyroidism. The mean 24 h cAMP excretion in patients with renal insufficiency was significantly decreased when compared to control subjects. These findings and recent reports confirm that the 24 h urinary output of cAMP may be considered an useful index of pharathyroid function in man.", "contents": "[The diagnostic value of the determination of cyclic 3',5'-adenosine monophosphate (cAMP) in urine]. Many hormones initiate their biologic actions by augmenting the intracellular concentrations of 3',5'-adenosine monophosphate (cyclic AMP). The nucleotide has been found in body fluids; its determination in plasma and urine can be performed by a rapid, simple and specific method: the cyclic AMP assay kit of the Radiochemical Centre (Amersham, England). The assay is based on the competition between unlabelled cAMP and a fixed quantity of the tritium labelled compound for binding to a bovine muscle protein which has a high specificity and affinity for cAMP. Different factors must be considered in evaluating the 24 h urinary content of the nucleotide: the renal or extrarenal origin of cAMP and the functional status of the kidneys. In basal conditions the urinary cAMP excretion is significantly correlated with creatinine excretion (n = 67; r = 0.47; p less than 0.001) thus confirming that the most part of cAMP excreted is derived from the plasma by glomerular filtration. Parathyroid hormone (PTH) stimulates adenylate cyclase predominantly in the renal cortex, whereas vasopressin (ADH) stimulated the enzyme in the medulla; thus PTH and ADH could increase the amount of cAMP in the urine from the renal source. In a case of diabetes insipidus and infusion of ADH caused a prompt rise in cAMP urinary excretion. In 5 normals an infusion of bovine synthetic parathyroid hormone caused an increased excretion of cAMP that preceded the phosphaturic response. An infusion of salmon synthetic calcitonin caused a rise in phosphate excretion and no increase in cAMP urinary content. As it concerns the two calciotopic hormones, PTH and CT, it is reasonable to assume that renal receptors are distinct. The 24 h urinary excretion of cAMP in 55 control subjects (3613 +/- 1460 D.S. n moles) was contrasted with the lower excretion in 25 elderly subjects (70-93 years: 1804 +/- 699 n moles), with the high cAMP excretion in a patient with hyperparathyroidism (that fell to normal values following removal of the parathyroid adenoma) and with the low cAMP excretion in patients with primary or surgical hypoparathyroidism. The mean 24 h cAMP excretion in patients with renal insufficiency was significantly decreased when compared to control subjects. These findings and recent reports confirm that the 24 h urinary output of cAMP may be considered an useful index of pharathyroid function in man."}
{"id": "PMID:190638", "title": "Arteritis following protracted supervoltage pelvic irradiation. Report of a case.", "content": "Arterial injuries attributed to irradiation are most frequent about the head and neck and are invariably triggered by infection, infarction, or fistulas. Vascular changes from surgery or invasive behavior of tumor can also contribute to local vascular insufficiencies. It is quite possible in humans that irradiation can accelerate the aging processes in atherosclerotic vessels. The case reported is unusual in that rather routine, postoperative, pelvic irradiation was given for pelvic soft tissue and bone carcinomatosis, only to be followed in 6 months to 1 year by vascular insufficiency symptoms in the lower extremities. Symptoms progressed to the point that surgical correction was contemplated, but then postponed when signs and symptoms improved following cessation of smoking. The patient had had no previous history of a Reynaud's diathesis. Although histologic proof is lacking (patient continues to do generally quite well 5 years following palliative treatment), field films and subsequent angiographic abnormalities can be superimposed almost exactly. Neither author is entirely happy with the diagnosis of 'radiation arteritis' for the reasons discussed, but the coincidence of radiation fields and areas of arterial damage makes the role of irradiation indicating.", "contents": "Arteritis following protracted supervoltage pelvic irradiation. Report of a case. Arterial injuries attributed to irradiation are most frequent about the head and neck and are invariably triggered by infection, infarction, or fistulas. Vascular changes from surgery or invasive behavior of tumor can also contribute to local vascular insufficiencies. It is quite possible in humans that irradiation can accelerate the aging processes in atherosclerotic vessels. The case reported is unusual in that rather routine, postoperative, pelvic irradiation was given for pelvic soft tissue and bone carcinomatosis, only to be followed in 6 months to 1 year by vascular insufficiency symptoms in the lower extremities. Symptoms progressed to the point that surgical correction was contemplated, but then postponed when signs and symptoms improved following cessation of smoking. The patient had had no previous history of a Reynaud's diathesis. Although histologic proof is lacking (patient continues to do generally quite well 5 years following palliative treatment), field films and subsequent angiographic abnormalities can be superimposed almost exactly. Neither author is entirely happy with the diagnosis of 'radiation arteritis' for the reasons discussed, but the coincidence of radiation fields and areas of arterial damage makes the role of irradiation indicating."}
{"id": "PMID:190640", "title": "Primary adenoid cystic carcinoma (cylindroma) of the trachea.", "content": "Two cases of adenoid cystic carcinoma of the trachea, and a review of the literature, are presented. This unusual and often undiagnosed tumor closely mimics asthma and chronic bronchitis. Although many patients die within 2 to 3 years of the onset of symptoms without appropriate treatment, adequate therapy should lead to survival of 10 years or more. The radiologist should make the initial diagnosis by noting the tumor, which is frequently located posterolaterally and in the middle third of the trachea.", "contents": "Primary adenoid cystic carcinoma (cylindroma) of the trachea. Two cases of adenoid cystic carcinoma of the trachea, and a review of the literature, are presented. This unusual and often undiagnosed tumor closely mimics asthma and chronic bronchitis. Although many patients die within 2 to 3 years of the onset of symptoms without appropriate treatment, adequate therapy should lead to survival of 10 years or more. The radiologist should make the initial diagnosis by noting the tumor, which is frequently located posterolaterally and in the middle third of the trachea."}
{"id": "PMID:190647", "title": "Cyclic AMP response to prostaglandin E1 in mononuclear cells from peripheral blood and synovial fluid of patients with rheumatoid arthritis.", "content": "The cyclic AMP response to prostaglandin E1 (PGE1) was studied in peripheral blood (PB) and synovial fluid (SF) mononuclear cells from patients with rheumatoid arthritis (RA). The PGE1 induced accumulation of cyclic AMP was consistently (7 of 8 patients) less in cell suspensions derived from SF than in suspensions of equivalent numbers of mononuclear cells obtained simultaneously from PB. The high PB/SF cyclic AMP ratio was seen most clearly at the lowest concentration (10(-6)M) of PGE1 tested. There was no correlation between the patients' therapy and cyclic AMP response to PGE1. The high PB/SF cyclic AMP ratio was not accounted for by the presence of platelets in PB cell suspensions.", "contents": "Cyclic AMP response to prostaglandin E1 in mononuclear cells from peripheral blood and synovial fluid of patients with rheumatoid arthritis. The cyclic AMP response to prostaglandin E1 (PGE1) was studied in peripheral blood (PB) and synovial fluid (SF) mononuclear cells from patients with rheumatoid arthritis (RA). The PGE1 induced accumulation of cyclic AMP was consistently (7 of 8 patients) less in cell suspensions derived from SF than in suspensions of equivalent numbers of mononuclear cells obtained simultaneously from PB. The high PB/SF cyclic AMP ratio was seen most clearly at the lowest concentration (10(-6)M) of PGE1 tested. There was no correlation between the patients' therapy and cyclic AMP response to PGE1. The high PB/SF cyclic AMP ratio was not accounted for by the presence of platelets in PB cell suspensions."}
{"id": "PMID:190648", "title": "Methyl xanthine phosphodiesterase inhibitors behave as prostaglandin antagonists in a perfused rat mesenteric artery preparation.", "content": "The methyl xanthines, theophylline, caffeine and 3-isobutyl-1 methyl xanthine (MIX) inhibited the pressure responses to noradrnealine, angiotensin II and potassium ions in the isolated perfused mesenteric vascular bed of the male rat. The ID50s for inhibition of responses to noradrenaline were 1.85 mug/ml (0.83 x 10(-5) M) for MIX, 18 mug/ml (1 x 10(-4)M) for theophylline and 133 mug/ml (6.8 x 10(-4) M) for caffeine. Similar ID50 concentrations were found for responses to angiotensin II and potassium. We have previously found that substances which inhibit the three pressor agents equally may be prostaglandin (PG) synthesis inhibitors or PG antagonists. Xanthine itself, cyclic AMP and dibutyrl cyclic AMP had no inhibitory effects on the preparation up to concentrations of 10-2 M. Partial inhibition of PG synthesis by indomethacin shifted the % inhibition/log concentration curve to the left, while addition of exogenous PGE2 shifted it to the right. In preparations completely inhibited by sufficient indomethacin added to the perfusate to block PG synthesis, and then restored by adding 1 or 5 ng/ml PGE2 in addition to the indomethacin, the methyl xanthines again inhibited responses suggesting that they were PG antagonists rather than inhibitors of synthesis or release. In preliminary experiments MIX also inhibited effects of PGF2alpha on rat uterus and PGE1 on guinea pig ileum. Effective concentrations of theophylline were similar to the therapeutic levels in human plasma. PG antagonists may be a major action of methyl xanthines requiring reinterpretation of many experiments which have attributed their effects to PDE inhibition. PGs may also be involved in regulating PDE action.", "contents": "Methyl xanthine phosphodiesterase inhibitors behave as prostaglandin antagonists in a perfused rat mesenteric artery preparation. The methyl xanthines, theophylline, caffeine and 3-isobutyl-1 methyl xanthine (MIX) inhibited the pressure responses to noradrnealine, angiotensin II and potassium ions in the isolated perfused mesenteric vascular bed of the male rat. The ID50s for inhibition of responses to noradrenaline were 1.85 mug/ml (0.83 x 10(-5) M) for MIX, 18 mug/ml (1 x 10(-4)M) for theophylline and 133 mug/ml (6.8 x 10(-4) M) for caffeine. Similar ID50 concentrations were found for responses to angiotensin II and potassium. We have previously found that substances which inhibit the three pressor agents equally may be prostaglandin (PG) synthesis inhibitors or PG antagonists. Xanthine itself, cyclic AMP and dibutyrl cyclic AMP had no inhibitory effects on the preparation up to concentrations of 10-2 M. Partial inhibition of PG synthesis by indomethacin shifted the % inhibition/log concentration curve to the left, while addition of exogenous PGE2 shifted it to the right. In preparations completely inhibited by sufficient indomethacin added to the perfusate to block PG synthesis, and then restored by adding 1 or 5 ng/ml PGE2 in addition to the indomethacin, the methyl xanthines again inhibited responses suggesting that they were PG antagonists rather than inhibitors of synthesis or release. In preliminary experiments MIX also inhibited effects of PGF2alpha on rat uterus and PGE1 on guinea pig ileum. Effective concentrations of theophylline were similar to the therapeutic levels in human plasma. PG antagonists may be a major action of methyl xanthines requiring reinterpretation of many experiments which have attributed their effects to PDE inhibition. PGs may also be involved in regulating PDE action."}
{"id": "PMID:190649", "title": "Elevation of prostaglandin and cyclic AMP levels by arachidonic acid in primary epithelial cell cultures of C3H mouse mammary tumors.", "content": "Arachidonic acid causes a sharp transient increase in cyclic AMP levels in primary epithelial cell cultures obtained from C3H mouse mammary tumors. The effect is evident within two minutes and is enhanced by theophylline or 3-isobutyl-1-methylxanthine. Maximum increase in cyclic AMP levels are observed with a dose of 100 mug/ml of arachidonic acid (AA). At higher dose levels the increase in cyclic AMP levels is reduced. Naproxen, an inhibitor of prostaglandin synthesis in this system markedly reduces the stimulation of cyclic AMP by arachidonic acid but it does not affect the increase in cyclic AMP levels observed after the addition of prostaglandin E's, epinephrine or cholera enterotoxin. Arachidonic acid, under the same conditions, also causes a significant elevation of PGE and PGF media levels which is slower and more sustained than the cAMP response. The data strongly suggest that a metabolic of arachidonic acid is responsible for the cyclic rise, however, it is not certain whether this is due to PGE2 or some other product.", "contents": "Elevation of prostaglandin and cyclic AMP levels by arachidonic acid in primary epithelial cell cultures of C3H mouse mammary tumors. Arachidonic acid causes a sharp transient increase in cyclic AMP levels in primary epithelial cell cultures obtained from C3H mouse mammary tumors. The effect is evident within two minutes and is enhanced by theophylline or 3-isobutyl-1-methylxanthine. Maximum increase in cyclic AMP levels are observed with a dose of 100 mug/ml of arachidonic acid (AA). At higher dose levels the increase in cyclic AMP levels is reduced. Naproxen, an inhibitor of prostaglandin synthesis in this system markedly reduces the stimulation of cyclic AMP by arachidonic acid but it does not affect the increase in cyclic AMP levels observed after the addition of prostaglandin E's, epinephrine or cholera enterotoxin. Arachidonic acid, under the same conditions, also causes a significant elevation of PGE and PGF media levels which is slower and more sustained than the cAMP response. The data strongly suggest that a metabolic of arachidonic acid is responsible for the cyclic rise, however, it is not certain whether this is due to PGE2 or some other product."}
{"id": "PMID:190650", "title": "Possible relation of prostaglandins to PMN-derived mediators of host metabolic responses to inflammation.", "content": "Stimulated rabbit peritoneal polymorphonuclear leukocyte (PMN) preparations simultaneously produce prostaglandin-like material and mediators that induce metabolic alterations in experimental animals characteristic of the host's responses to inflammation. The alterations observed in rats include responses by: proteins, carbohydrates, hormones, trace metals, and total blood neutrophils. This study demonstrates a possible relationship between prostaglandins and PMN-derived substances that mediate plasma zinc depression, hepatic amino acid uptake, and increased numbers of blood neutrophils. Production of these mediators by stimulated-PMN preparations was prevented by 23 muM indomethacin or 93 muM aspirin. Conversely, morphine (2 mM or less) had no detrimental effect on production of these mediators, although, it consistently stimulated production of a substance stimulating total blood neutrophia. In addition, 2 muM prostaglandin E and F stimulated production of substances mediating hepatic amino acid uptake plasma zinc depression, respectively. At this concentration, neither prostaglandin significantly altered production of substances mediating increased numbers of total blood neutrophils. A partial-nitrogen atmosphere, dibutyryl cyclic analogs of AMP and GMP, or homogenization of the PMN had no effect on mediator production. The inhibitory effect of indomethacin and aspirin also was observed with PMN-homogenastes. These experimental observations suggest that prostaglandin synthesis has a function in production of mediators by stimulated-PMN preparations.", "contents": "Possible relation of prostaglandins to PMN-derived mediators of host metabolic responses to inflammation. Stimulated rabbit peritoneal polymorphonuclear leukocyte (PMN) preparations simultaneously produce prostaglandin-like material and mediators that induce metabolic alterations in experimental animals characteristic of the host's responses to inflammation. The alterations observed in rats include responses by: proteins, carbohydrates, hormones, trace metals, and total blood neutrophils. This study demonstrates a possible relationship between prostaglandins and PMN-derived substances that mediate plasma zinc depression, hepatic amino acid uptake, and increased numbers of blood neutrophils. Production of these mediators by stimulated-PMN preparations was prevented by 23 muM indomethacin or 93 muM aspirin. Conversely, morphine (2 mM or less) had no detrimental effect on production of these mediators, although, it consistently stimulated production of a substance stimulating total blood neutrophia. In addition, 2 muM prostaglandin E and F stimulated production of substances mediating hepatic amino acid uptake plasma zinc depression, respectively. At this concentration, neither prostaglandin significantly altered production of substances mediating increased numbers of total blood neutrophils. A partial-nitrogen atmosphere, dibutyryl cyclic analogs of AMP and GMP, or homogenization of the PMN had no effect on mediator production. The inhibitory effect of indomethacin and aspirin also was observed with PMN-homogenastes. These experimental observations suggest that prostaglandin synthesis has a function in production of mediators by stimulated-PMN preparations."}
{"id": "PMID:190652", "title": "Characterization of tumour virus proteins. I. Radioimmunoassay of the P27 protein of avian viruses.", "content": "The major structural protein of avian oncornaviruses, a core component of about 27000 daltons, has been measured by radioimmunoassay. The purified protein was labelled with 125Iodine by chloramine-T method. The immune serum titer was defined as the highest serum dilution able to precipitate 50% of the labelled antigen present in the system. Standard competition curve was constructed in order to determine the equivalents of protein, in a system with limiting antibody concentration. In the experimental conditions used, 0.14 ng of AMV-P27 inhibited 50% of 125I-AMV-P27 (1.0 ng) precipitation. The 125I-AMV-P27 vs anti-AMV-P27 system was used to study the competition of normal cells, purified virus suspension, productive cells and supernatant fluids. Most of the chicken embryo fibroblasts showed expression of this viral component. The phenomena of cell transformation, the increase in total protein, and the expression of P27 were studied in rapid transformation of CEF by RSV-SRA.", "contents": "Characterization of tumour virus proteins. I. Radioimmunoassay of the P27 protein of avian viruses. The major structural protein of avian oncornaviruses, a core component of about 27000 daltons, has been measured by radioimmunoassay. The purified protein was labelled with 125Iodine by chloramine-T method. The immune serum titer was defined as the highest serum dilution able to precipitate 50% of the labelled antigen present in the system. Standard competition curve was constructed in order to determine the equivalents of protein, in a system with limiting antibody concentration. In the experimental conditions used, 0.14 ng of AMV-P27 inhibited 50% of 125I-AMV-P27 (1.0 ng) precipitation. The 125I-AMV-P27 vs anti-AMV-P27 system was used to study the competition of normal cells, purified virus suspension, productive cells and supernatant fluids. Most of the chicken embryo fibroblasts showed expression of this viral component. The phenomena of cell transformation, the increase in total protein, and the expression of P27 were studied in rapid transformation of CEF by RSV-SRA."}
{"id": "PMID:190657", "title": "Effect of paraquat on rat lung prolyl hydroxylase.", "content": "Acute administration of Paraquat (25 mg/kg, I.P.) was found to significantly increase prolyl hydroxylase in rat lung 7 days following treatment. There was no change in total collagen at this time point. At 21 days following drug treatment, total collagen was significantly elevated while prolyl hydroxylase activity had returned to control level.", "contents": "Effect of paraquat on rat lung prolyl hydroxylase. Acute administration of Paraquat (25 mg/kg, I.P.) was found to significantly increase prolyl hydroxylase in rat lung 7 days following treatment. There was no change in total collagen at this time point. At 21 days following drug treatment, total collagen was significantly elevated while prolyl hydroxylase activity had returned to control level."}
{"id": "PMID:190658", "title": "Detection of rotavirus in experimentally infected piglets.", "content": "Scouring and vomiting was induced in piglets by experimental infection with a field strain of rotavirus. Virus or viral antigen was detected in the small intestine by the fluorescent antibody technique and virus could also be demonstrated in infected tissue culture cells by immuno-fluorescence. Progeny particles in the epithelial layer of the small intestine were identified by electron microscopy. Three morphological types could be distinguished, often associated with electron-dense inclusion, and infected cells, though small in number, were present throughout the length of the small intestine.", "contents": "Detection of rotavirus in experimentally infected piglets. Scouring and vomiting was induced in piglets by experimental infection with a field strain of rotavirus. Virus or viral antigen was detected in the small intestine by the fluorescent antibody technique and virus could also be demonstrated in infected tissue culture cells by immuno-fluorescence. Progeny particles in the epithelial layer of the small intestine were identified by electron microscopy. Three morphological types could be distinguished, often associated with electron-dense inclusion, and infected cells, though small in number, were present throughout the length of the small intestine."}
{"id": "PMID:190653", "title": "[Viral flora (coliphages and human enteroviruses) found in river water after an urban district (Saint-Etienne). I. Comparative study of four simple and inexpensive methods for concentration and isolation of river-water viruses (author's transl)].", "content": "Four methods for the concentration of human enteroviruses in the waters of the river Furan were surveyed: the original method described by WALLIS, of adsorption of viruses on PE-60 polyelectrolyte; a modified version of the Wallis method; a method using a different polyelectrolyte available in France, the POE; the two-phase system described by SHUVAL. The best results were obtained when using the method of adsorption on polyelectrolytes, and the second method was finally chosen for field surveys.", "contents": "[Viral flora (coliphages and human enteroviruses) found in river water after an urban district (Saint-Etienne). I. Comparative study of four simple and inexpensive methods for concentration and isolation of river-water viruses (author's transl)]. Four methods for the concentration of human enteroviruses in the waters of the river Furan were surveyed: the original method described by WALLIS, of adsorption of viruses on PE-60 polyelectrolyte; a modified version of the Wallis method; a method using a different polyelectrolyte available in France, the POE; the two-phase system described by SHUVAL. The best results were obtained when using the method of adsorption on polyelectrolytes, and the second method was finally chosen for field surveys."}
{"id": "PMID:190654", "title": "[Viral flora (coliphages and human enteroviruses) found in river water after an urban district (Saint-Etienne). II. A virological and epidemiological survey (author's transl)].", "content": "A survey was carried out from March 1972 to February 1973 to identify viral flora found in the river Furan ater St. Etienne. The 54 samples examined revealed the following data: 1) more accurate results are obtained when viral concentration values are expressed in terms of m3/sec., taking into account the flow of the river and eliminating the seasonal dilution factor; 2) rates of enteroviruses remain constant throughout the year, in spite of a relatively rapid spontaneous inactivation of the viruses; 3) rates of coliphages vary considerably according to seasons, with a notable increase in summer; 4) the two previous data are unrelated; 5) 147 enterovirus strains were isolated, of which 44% were polioviruses; 6) virulent and attenuated types 2 and 3 polioviruses were found simultaneously at certain periods; 7) only virulent strains of type 1 poliovirus were isolated; 8) this type of survey may be useful in controlling the endemic residual poliomyelitis in the region of St. Etienne.", "contents": "[Viral flora (coliphages and human enteroviruses) found in river water after an urban district (Saint-Etienne). II. A virological and epidemiological survey (author's transl)]. A survey was carried out from March 1972 to February 1973 to identify viral flora found in the river Furan ater St. Etienne. The 54 samples examined revealed the following data: 1) more accurate results are obtained when viral concentration values are expressed in terms of m3/sec., taking into account the flow of the river and eliminating the seasonal dilution factor; 2) rates of enteroviruses remain constant throughout the year, in spite of a relatively rapid spontaneous inactivation of the viruses; 3) rates of coliphages vary considerably according to seasons, with a notable increase in summer; 4) the two previous data are unrelated; 5) 147 enterovirus strains were isolated, of which 44% were polioviruses; 6) virulent and attenuated types 2 and 3 polioviruses were found simultaneously at certain periods; 7) only virulent strains of type 1 poliovirus were isolated; 8) this type of survey may be useful in controlling the endemic residual poliomyelitis in the region of St. Etienne."}
{"id": "PMID:190659", "title": "Lecithin--cholesterol--acyltransferase activity in the plasma of immature, oestrogenised and laying fowl (Gallus domesticus).", "content": "A study was made of the role of the lecithin-cholesterol-acyltransferase (LCAT) enzyme in the changes in the concentrations and fatty acid composition of the plasma cholesteryl esters of the fowl associated with oestrogen treatment and sexual maturity. Although there was a considerable increase in the concentration of free cholesterol in the plasma of  oestrogen treated and laying birds, only in the oestrogen treated birds was it associated with an increased rate of cholesterol esterification. In both laying and oestrogen treated birds, changes in the fatty acid composition of the plasma cholesterol esters could be attributed to related changes in  the fatty acid specificity of the LCAT enzyme. Evidence is provided to indicate that the cholesterol esters in the plasma of the fowl are synthesised mainly by the plasma LCAT system. The changes in the rates and fatty acid specificity of the LCAT system in the plasma of the fowl associated with sexual maturity or oestrogen treatment are discussed in relation to the extensive alterations shown to occur in the lipoprotein pattern of the plasma.", "contents": "Lecithin--cholesterol--acyltransferase activity in the plasma of immature, oestrogenised and laying fowl (Gallus domesticus). A study was made of the role of the lecithin-cholesterol-acyltransferase (LCAT) enzyme in the changes in the concentrations and fatty acid composition of the plasma cholesteryl esters of the fowl associated with oestrogen treatment and sexual maturity. Although there was a considerable increase in the concentration of free cholesterol in the plasma of  oestrogen treated and laying birds, only in the oestrogen treated birds was it associated with an increased rate of cholesterol esterification. In both laying and oestrogen treated birds, changes in the fatty acid composition of the plasma cholesterol esters could be attributed to related changes in  the fatty acid specificity of the LCAT enzyme. Evidence is provided to indicate that the cholesterol esters in the plasma of the fowl are synthesised mainly by the plasma LCAT system. The changes in the rates and fatty acid specificity of the LCAT system in the plasma of the fowl associated with sexual maturity or oestrogen treatment are discussed in relation to the extensive alterations shown to occur in the lipoprotein pattern of the plasma."}
{"id": "PMID:190660", "title": "In vitro stimulation of bovine circulating lymphocytes by parainfluenza type 3 virus.", "content": "Bovine circulating lymphocytes from animals sero-positive to parainfluenza-3 virus (PIV-3) could be stimulated by PIV-3 antigen in a microculture system. A semiautomatic multiple sample harvester was used to collect the lymphocytes from the microplates. Ultraviolet-killed PIV-3 induced better stimulation values than formalin or heat-treated virus. The highest stimulation values were obtained after a stimulation time of three to five days.", "contents": "In vitro stimulation of bovine circulating lymphocytes by parainfluenza type 3 virus. Bovine circulating lymphocytes from animals sero-positive to parainfluenza-3 virus (PIV-3) could be stimulated by PIV-3 antigen in a microculture system. A semiautomatic multiple sample harvester was used to collect the lymphocytes from the microplates. Ultraviolet-killed PIV-3 induced better stimulation values than formalin or heat-treated virus. The highest stimulation values were obtained after a stimulation time of three to five days."}
{"id": "PMID:190661", "title": "Effects of starvation, surgery and infusion of adrenocorticotrophin on plasma amino acid concentration in the pregnant ewe.", "content": "Total plasma amino acid concentrations (TAA) in 12 Scottish Blackface ewes between 80 and 140 days of pregnancy were unaltered by two days of starvation, but concentrations of essential amino acids (EAA) increased and non-essential amino acid (NAA) levels decreased. These trends were more pronounced later in pregnancy. Ewes fasted before surgery to implant fetal catheters showed marked reductions in mean TAA levels (--26 per cent, n-5) on the day after operation (day+ 1). Half of this decrease was accounted for by glycine. Mean concentrations of NAA increased after day +1 but by day +6 were still 15 per cent below baseline values. In contrast mean plasma concentrations of EAA were 31 per cent above prestarvation  levels on day +6 and maximal on day +4(+39 per cent). Following a two-day fast, sheep given half rations and simultaneously infused with adrenocorticotrophin showed changes in plasma-free amino acid composition like those observed during the two days after operation. Disturbances to plasma amino acid concetrations persisted for up to 12 days after operation and are attributed to the preoperative starvation and the combined effects of irregular feeding patterns and elevated plasma corticosteroid levels during and after operation.", "contents": "Effects of starvation, surgery and infusion of adrenocorticotrophin on plasma amino acid concentration in the pregnant ewe. Total plasma amino acid concentrations (TAA) in 12 Scottish Blackface ewes between 80 and 140 days of pregnancy were unaltered by two days of starvation, but concentrations of essential amino acids (EAA) increased and non-essential amino acid (NAA) levels decreased. These trends were more pronounced later in pregnancy. Ewes fasted before surgery to implant fetal catheters showed marked reductions in mean TAA levels (--26 per cent, n-5) on the day after operation (day+ 1). Half of this decrease was accounted for by glycine. Mean concentrations of NAA increased after day +1 but by day +6 were still 15 per cent below baseline values. In contrast mean plasma concentrations of EAA were 31 per cent above prestarvation  levels on day +6 and maximal on day +4(+39 per cent). Following a two-day fast, sheep given half rations and simultaneously infused with adrenocorticotrophin showed changes in plasma-free amino acid composition like those observed during the two days after operation. Disturbances to plasma amino acid concetrations persisted for up to 12 days after operation and are attributed to the preoperative starvation and the combined effects of irregular feeding patterns and elevated plasma corticosteroid levels during and after operation."}
{"id": "PMID:190667", "title": "[Use and effectiveness of scintigraphy, sonography and angiography in circumscribed disease of the liver (author's transl)].", "content": "The effectiveness of scintigraphy, sonography and angiography is compared in a material of 140 cases of circumscribed disease of the liver. Typical clinical starting points are defined as points of reference of the diagnostic techniques. Clinical diagnosis is very safe in cases of secondary blastoma and hepatocellular carcinoma of the liver. Since the great majority of these conditions cause space-occupying lesions of the liver, problems of radiologic diagnosis are confined to the smaller number of clinically ill-defined lesions. For the diagnosis of secondary blastomas and cystic process of all kinds, scintigraphy and sonography are not improved by angiography. Solid space-occupying lesions of unknown origin, however, can only be recognized with angiography. Histology of both benign and malignant processes will be correct in more than 90% of cases.", "contents": "[Use and effectiveness of scintigraphy, sonography and angiography in circumscribed disease of the liver (author's transl)]. The effectiveness of scintigraphy, sonography and angiography is compared in a material of 140 cases of circumscribed disease of the liver. Typical clinical starting points are defined as points of reference of the diagnostic techniques. Clinical diagnosis is very safe in cases of secondary blastoma and hepatocellular carcinoma of the liver. Since the great majority of these conditions cause space-occupying lesions of the liver, problems of radiologic diagnosis are confined to the smaller number of clinically ill-defined lesions. For the diagnosis of secondary blastomas and cystic process of all kinds, scintigraphy and sonography are not improved by angiography. Solid space-occupying lesions of unknown origin, however, can only be recognized with angiography. Histology of both benign and malignant processes will be correct in more than 90% of cases."}
{"id": "PMID:190669", "title": "[Mandibular metastasis disclosing a primary cancer of the liver].", "content": "The authors describe a new case of mandibular metastasis of a hepatome. They recall that these metastases indicate tumour and that they are generally haemorrhagic. Diagnosis is confirmed by means of biopsy, but the scanner or echotomography and angiography reveal the primary lesion. Investigation using marked technetium pyrophosphate is essential to screen for further osseous lesions.", "contents": "[Mandibular metastasis disclosing a primary cancer of the liver]. The authors describe a new case of mandibular metastasis of a hepatome. They recall that these metastases indicate tumour and that they are generally haemorrhagic. Diagnosis is confirmed by means of biopsy, but the scanner or echotomography and angiography reveal the primary lesion. Investigation using marked technetium pyrophosphate is essential to screen for further osseous lesions."}
{"id": "PMID:190670", "title": "The visibly fluorescent phospholipids of serum lipoproteins.", "content": "The blusih-white fluorescence exhibited by lipoproteins from human serum has been investigated. It appears that high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low density lipoprotein (VLDL) all exhibit this fluorescence with excitation maximum at about 360 nm and fluorescence maximum at about 450 nm. The fluorescence resides in the phospholipid fraction of the lipoproteins and is not located in the fatty acids, since the water-soluble deacylated phospholipid fraction exhibited the same fluorescence. Upon electrophoresis of this fraction at pH 6.5 the fluorescent material carried a negative charge and moved a distance similar to glycerophosphoserine and glycerophosphoinositol, which both carry one negative charge. This negatively charged fluorescent product is ninhydrine negative, and gives a positive reaction for phosphate esters and 1,2-glycols. The detailed structure of the fluorescent product is not yet known. It is suggested that reactive aldehydes are involved in its formation from the aminophosphatides. Its possible relationship to tissue peroxidation is discussed.", "contents": "The visibly fluorescent phospholipids of serum lipoproteins. The blusih-white fluorescence exhibited by lipoproteins from human serum has been investigated. It appears that high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low density lipoprotein (VLDL) all exhibit this fluorescence with excitation maximum at about 360 nm and fluorescence maximum at about 450 nm. The fluorescence resides in the phospholipid fraction of the lipoproteins and is not located in the fatty acids, since the water-soluble deacylated phospholipid fraction exhibited the same fluorescence. Upon electrophoresis of this fraction at pH 6.5 the fluorescent material carried a negative charge and moved a distance similar to glycerophosphoserine and glycerophosphoinositol, which both carry one negative charge. This negatively charged fluorescent product is ninhydrine negative, and gives a positive reaction for phosphate esters and 1,2-glycols. The detailed structure of the fluorescent product is not yet known. It is suggested that reactive aldehydes are involved in its formation from the aminophosphatides. Its possible relationship to tissue peroxidation is discussed."}
{"id": "PMID:190671", "title": "Effect on caries of daily supervised toothbrushing with sodium monofluorophosphate and sodium fluoride dentifrices after 3 years.", "content": "In a 3-year clinical trial the effect of daily supervised toothbrushing with a dentifrice containing sodium fluoride/silicon dioxide and a dentifrice containing sodium monofluorophosphate/calcium phosphate and calcium carbonate was investigated. Initially about 400 children aged 9-11 years from one school in Malm\u00f6 took part in the study. They were randomly divided into two groups. Each group brushed their teeth daily in school under the supervision of a dental hygienist. The children and their families were given the corresponding dentifrices for home use. The children were examined for caries at the start of the study and again after an interval of 1 year by the same dentist and according to the stated criteria. A comparison of the caries increments in the two dentifrice groups revealed a statistically significantly lower caries increment during the 2nd and 3rd experimental years in the sodium fluoride dentifrice group compared with the sodium monofluorophosphate dentifrice group.", "contents": "Effect on caries of daily supervised toothbrushing with sodium monofluorophosphate and sodium fluoride dentifrices after 3 years. In a 3-year clinical trial the effect of daily supervised toothbrushing with a dentifrice containing sodium fluoride/silicon dioxide and a dentifrice containing sodium monofluorophosphate/calcium phosphate and calcium carbonate was investigated. Initially about 400 children aged 9-11 years from one school in Malm\u00f6 took part in the study. They were randomly divided into two groups. Each group brushed their teeth daily in school under the supervision of a dental hygienist. The children and their families were given the corresponding dentifrices for home use. The children were examined for caries at the start of the study and again after an interval of 1 year by the same dentist and according to the stated criteria. A comparison of the caries increments in the two dentifrice groups revealed a statistically significantly lower caries increment during the 2nd and 3rd experimental years in the sodium fluoride dentifrice group compared with the sodium monofluorophosphate dentifrice group."}
{"id": "PMID:190672", "title": "Serum myeloperoxidase and lactoferrin in neutropenia.", "content": "Radioimmunosorbent assays for determination of serum content of the neutrophil proteins myeloperoxidase and lactoferrin are described. Serial studies were performed in patients with neutropenia. In 2 cases of cyclic neutropenia the myeloperoxidase level showed slight variations within the normal range during the cycle while lactoferrin displayed a clear correlation with neutrophil counts. In 1 case with persistent agranulocytosis myeloperoxidase was normal but lactoferrin was extremely low. During the regeneration phase of drug-induced neutropenia neutrophil counts and serum lactoferrin increased in a parallel fashion. Since serum myeloperoxidase was normal during profounded neutropenia it is suggested to derive primarily from myeloperoxidase-rich granulopoietic precursor cells of the marrow. Serum lactoferrin  on the other hand seems to derive from leakage of more granulopoietic cells of blood and marrow. Studies of neutrophil proteins of serum may aid in evaluation  of neutropenic patients.", "contents": "Serum myeloperoxidase and lactoferrin in neutropenia. Radioimmunosorbent assays for determination of serum content of the neutrophil proteins myeloperoxidase and lactoferrin are described. Serial studies were performed in patients with neutropenia. In 2 cases of cyclic neutropenia the myeloperoxidase level showed slight variations within the normal range during the cycle while lactoferrin displayed a clear correlation with neutrophil counts. In 1 case with persistent agranulocytosis myeloperoxidase was normal but lactoferrin was extremely low. During the regeneration phase of drug-induced neutropenia neutrophil counts and serum lactoferrin increased in a parallel fashion. Since serum myeloperoxidase was normal during profounded neutropenia it is suggested to derive primarily from myeloperoxidase-rich granulopoietic precursor cells of the marrow. Serum lactoferrin  on the other hand seems to derive from leakage of more granulopoietic cells of blood and marrow. Studies of neutrophil proteins of serum may aid in evaluation  of neutropenic patients."}
{"id": "PMID:190673", "title": "Myeloperoxidase and lactoferrin of blood neutrophils and plasma in chronic granulocytic leukaemia.", "content": "Myeloperoxidase, restricted to primary granules, and lactoferrin, restricted to secondary granules, were determined in plasma and neutrophils of peripheral blood in chronic granulocytic leukaemia (CGL). Plasma myeloperoxidase was increased 2-3 times while plasma lactoferrin increased 2-8 times. This discrepancy indicates different modes of release or elimination. A correlation was found between the leucocyte count and plasma myeloperoxidase or lactoferrin. A correlation was also found between cellular and plasma levels of lactoferrin but not for myeloperoxidase indicating the source for plasma lactoferrin to be circulating leucocytes, which may not be the case for plasma myeloperoxidase. Decreased neutrophil lactoferrin was found in 71% of the CGL cases while myeloperoxidase was decreased in 18%. Serial studies on individual CGL subjects showed low cellular lactoferrin during phases with rapidly expanding leucocytosis indicating defective maturation of neutrophils or abnormal release because of prolonged intravascular life-span.", "contents": "Myeloperoxidase and lactoferrin of blood neutrophils and plasma in chronic granulocytic leukaemia. Myeloperoxidase, restricted to primary granules, and lactoferrin, restricted to secondary granules, were determined in plasma and neutrophils of peripheral blood in chronic granulocytic leukaemia (CGL). Plasma myeloperoxidase was increased 2-3 times while plasma lactoferrin increased 2-8 times. This discrepancy indicates different modes of release or elimination. A correlation was found between the leucocyte count and plasma myeloperoxidase or lactoferrin. A correlation was also found between cellular and plasma levels of lactoferrin but not for myeloperoxidase indicating the source for plasma lactoferrin to be circulating leucocytes, which may not be the case for plasma myeloperoxidase. Decreased neutrophil lactoferrin was found in 71% of the CGL cases while myeloperoxidase was decreased in 18%. Serial studies on individual CGL subjects showed low cellular lactoferrin during phases with rapidly expanding leucocytosis indicating defective maturation of neutrophils or abnormal release because of prolonged intravascular life-span."}
{"id": "PMID:190674", "title": "Tremor caused by sympathomimetics is mediated by beta2-adrenoreceptors.", "content": "Tremor caused by beta-adrenostimulating drugs is known to be mediated by beta-receptors in skeletal muscles. In this study it was shown that tremor caused by terbutaline could be blocked by propranolol, a drug with both beta1- and beta2-blocking properties, but not by metoprolol, a beta1-selective antagonist. It is concluded that tremor caused by sympathomimetics in man is mainly mediated by beta2-receptors.", "contents": "Tremor caused by sympathomimetics is mediated by beta2-adrenoreceptors. Tremor caused by beta-adrenostimulating drugs is known to be mediated by beta-receptors in skeletal muscles. In this study it was shown that tremor caused by terbutaline could be blocked by propranolol, a drug with both beta1- and beta2-blocking properties, but not by metoprolol, a beta1-selective antagonist. It is concluded that tremor caused by sympathomimetics in man is mainly mediated by beta2-receptors."}
{"id": "PMID:190677", "title": "Selective display of histamine receptors on lymphocytes.", "content": "Histamine, acting on histamine type 2 receptors, increases intracellular cyclic adenosine monophosphate (AMP) and thus modulates the immunologic functions of lymphocytes. Lymphocyte cyclic AMP levels were used to follow the development of histamine receptors. The B lymphocytes have no functional histamine receptors. As T lymphocytes \"mature\" in immunologic function--from thymocytes to cortisone-resistant thymocytes to splenic T lymphocytes--their response to histamine increases. The response of these subpopulations of lymphocytes to isoproterenol is the inverse of the histamine response. It is suggested that the changing display of histamine receptors plays an important part in the control of immunologic responses.", "contents": "Selective display of histamine receptors on lymphocytes. Histamine, acting on histamine type 2 receptors, increases intracellular cyclic adenosine monophosphate (AMP) and thus modulates the immunologic functions of lymphocytes. Lymphocyte cyclic AMP levels were used to follow the development of histamine receptors. The B lymphocytes have no functional histamine receptors. As T lymphocytes \"mature\" in immunologic function--from thymocytes to cortisone-resistant thymocytes to splenic T lymphocytes--their response to histamine increases. The response of these subpopulations of lymphocytes to isoproterenol is the inverse of the histamine response. It is suggested that the changing display of histamine receptors plays an important part in the control of immunologic responses."}
{"id": "PMID:190678", "title": "Regeneration of oligodendroglia during recovery from demyelinating disease.", "content": "Infection of mice with the JHM strain of mouse hepatitis virus causes demyelination as a result of a cytolytic infection of oligodendroglia. In recovery, animals show remyelination, which could result either from surviving oligodendrocytes extending their territory or by generation of new oligodendroglia. Electron microscopic autoradiographic studies with 3H-labeled thymidine demonstrate that the cells associated with remyelination are newly generated oligodendroglia.", "contents": "Regeneration of oligodendroglia during recovery from demyelinating disease. Infection of mice with the JHM strain of mouse hepatitis virus causes demyelination as a result of a cytolytic infection of oligodendroglia. In recovery, animals show remyelination, which could result either from surviving oligodendrocytes extending their territory or by generation of new oligodendroglia. Electron microscopic autoradiographic studies with 3H-labeled thymidine demonstrate that the cells associated with remyelination are newly generated oligodendroglia."}
{"id": "PMID:190679", "title": "Arginyl residues: anion recognition sites in enzymes.", "content": "Chemical modification with 2,3-butanedione in borate buffer indicates that nine of ten glycolytic enzymes studied contain arginyl residues at their active sites. Fructose-1,6-diphosphatase also has arginines at its binding site for the allosteric inhibitor, adenosine monophosphate. These and other data suggest that, as a general rule, enzymes acting on anionic substrates or cofactors will probably contain arginyl residues as components of their ligand binding sites. This could account in part for the relatively infrequent occurrence of arginine in proteins.", "contents": "Arginyl residues: anion recognition sites in enzymes. Chemical modification with 2,3-butanedione in borate buffer indicates that nine of ten glycolytic enzymes studied contain arginyl residues at their active sites. Fructose-1,6-diphosphatase also has arginines at its binding site for the allosteric inhibitor, adenosine monophosphate. These and other data suggest that, as a general rule, enzymes acting on anionic substrates or cofactors will probably contain arginyl residues as components of their ligand binding sites. This could account in part for the relatively infrequent occurrence of arginine in proteins."}
{"id": "PMID:190680", "title": "Superhelix densities of circular DNA's: a generalized equation for their determination by the bouyant method.", "content": "Equations for the measurement of the supertwisting of circular DNA's from banding positions in buoyant density gradients containing intercalating dyes have required the use of SV40 DNA isolated from virions as a reference DNA. These equations are modified to allow the use of any closed circular DNA of known superhelix density as a reference DNA.", "contents": "Superhelix densities of circular DNA's: a generalized equation for their determination by the bouyant method. Equations for the measurement of the supertwisting of circular DNA's from banding positions in buoyant density gradients containing intercalating dyes have required the use of SV40 DNA isolated from virions as a reference DNA. These equations are modified to allow the use of any closed circular DNA of known superhelix density as a reference DNA."}
{"id": "PMID:190681", "title": "Amplitude spectrum representation in the Doppler-shifted-CF processing area of the auditory cortex of the mustache bat.", "content": "The mustache bat, Pteronotus parnellii rubiginosus, emits orientation sounds containing a long constant-frequency (CF) component that is ideal for echo detection and Doppler shift measurement. About 30 percent of the primary auditory cortex of this bat is chiefly devoted to processing the second harmonic of the CF component in Doppler-shifted echoes. In this Doppler-shifted-CF processing area, single neurons recorded in any electrode penetration perpendicular to the cortical surface have nearly identical best frequencies and best amplitudes (or best pressure levels) at which the neurons show maximum excitation. The best frequency and best amplitude vary systematically with the location of the neurons in the cerebral cortex, so that there are tonotopic and \"amplitopic\" representation axes, which are radial and eccentric, respectively. In other words, the best-frequency and best-amplitude contours are eccentric and radial, respectively. The amplitude spectrum of a signal is thus represented in the coordinates of amplitude and frequency parallel to the cortical surface. This amplitude spectrum representation is disproportionate according to perceptual significance, so that a signal of 61.5 to 62.0 kilohertz and 30 to 50 decibels SPL (sound pressure level) is projected to a larger area than other signals. Just outside this Doppler-shifted-CF processing area, neurons are found which are specialized for responding to a particular information-bearing element or a particular combination of information-bearing elements in orientation sounds and echoes consisting of CF and frequency-modulated components.", "contents": "Amplitude spectrum representation in the Doppler-shifted-CF processing area of the auditory cortex of the mustache bat. The mustache bat, Pteronotus parnellii rubiginosus, emits orientation sounds containing a long constant-frequency (CF) component that is ideal for echo detection and Doppler shift measurement. About 30 percent of the primary auditory cortex of this bat is chiefly devoted to processing the second harmonic of the CF component in Doppler-shifted echoes. In this Doppler-shifted-CF processing area, single neurons recorded in any electrode penetration perpendicular to the cortical surface have nearly identical best frequencies and best amplitudes (or best pressure levels) at which the neurons show maximum excitation. The best frequency and best amplitude vary systematically with the location of the neurons in the cerebral cortex, so that there are tonotopic and \"amplitopic\" representation axes, which are radial and eccentric, respectively. In other words, the best-frequency and best-amplitude contours are eccentric and radial, respectively. The amplitude spectrum of a signal is thus represented in the coordinates of amplitude and frequency parallel to the cortical surface. This amplitude spectrum representation is disproportionate according to perceptual significance, so that a signal of 61.5 to 62.0 kilohertz and 30 to 50 decibels SPL (sound pressure level) is projected to a larger area than other signals. Just outside this Doppler-shifted-CF processing area, neurons are found which are specialized for responding to a particular information-bearing element or a particular combination of information-bearing elements in orientation sounds and echoes consisting of CF and frequency-modulated components."}
{"id": "PMID:190682", "title": "Bile, prolactin, and the maternal pheromone.", "content": "When bile from females that had been lactating for 21 days was injected into the cecum of male rats it induced release of a maternal pheromone. Males injected with bile drawn from females in which prolactin had been inhibited, or from females that had been lactating for only 5 days, did not emit the pheromone. These data suggest a sex difference in the way prolactin alters the composition of bile so that the female can emit the maternal pheromone while the male normally cannot.", "contents": "Bile, prolactin, and the maternal pheromone. When bile from females that had been lactating for 21 days was injected into the cecum of male rats it induced release of a maternal pheromone. Males injected with bile drawn from females in which prolactin had been inhibited, or from females that had been lactating for only 5 days, did not emit the pheromone. These data suggest a sex difference in the way prolactin alters the composition of bile so that the female can emit the maternal pheromone while the male normally cannot."}
{"id": "PMID:190683", "title": "An analog of enkephalin having prolonged opiate-like effects in vivo.", "content": "Intraventricular administration of the enkephalin analog, [D-Ala2]-metenkephalin, induces profound and long-lasting analgesia, as well as other opiate-like behavioral effects in the rat. This analgesia was highly dose dependent, of much greater magnitude, and about 30 times longer lasting than that produced by the naturally occurring peptide, methionine-enkephalin. The behavioral effects of the [D-Ala2] analog could be completely reversed by the opiate antagonist, naloxone, suggesting that these effects were mediated by opiate receptors. Systemic administration of naloxone alone resulted in a significant increase in pain sensitivity. These findings support the view that endogenous opiate systems may play an important role in modulating pain sensitivity.", "contents": "An analog of enkephalin having prolonged opiate-like effects in vivo. Intraventricular administration of the enkephalin analog, [D-Ala2]-metenkephalin, induces profound and long-lasting analgesia, as well as other opiate-like behavioral effects in the rat. This analgesia was highly dose dependent, of much greater magnitude, and about 30 times longer lasting than that produced by the naturally occurring peptide, methionine-enkephalin. The behavioral effects of the [D-Ala2] analog could be completely reversed by the opiate antagonist, naloxone, suggesting that these effects were mediated by opiate receptors. Systemic administration of naloxone alone resulted in a significant increase in pain sensitivity. These findings support the view that endogenous opiate systems may play an important role in modulating pain sensitivity."}
{"id": "PMID:190684", "title": "[Dupuytren's contracture and palmar erythema in alcoholic cirrhosis].", "content": "Three comparable groups were studied : 100 patients with alcoholic cirrhosis, 100 alcoholics without cirrhosis, and 100 subjects without either alcoholism or cirrhosis. Dupuytren's contracture was noted in 43% of cases in group I, 34% in group 2, and in 14% of group 3. There was no parallel between the frequency of Dupuytren's contracture and the severity of the liver involvement. Palmar erythema was noted in 34% of cases of group 1, 23% of cases of group 2, 12% of cases of group 3. Dupuytren's contracture has a genetic background, but its clinical expression is facilitated by metabolic causes, the most frequent being chronic alcoholism. Palmar erythema appears to be a sign of severe liver disease.", "contents": "[Dupuytren's contracture and palmar erythema in alcoholic cirrhosis]. Three comparable groups were studied : 100 patients with alcoholic cirrhosis, 100 alcoholics without cirrhosis, and 100 subjects without either alcoholism or cirrhosis. Dupuytren's contracture was noted in 43% of cases in group I, 34% in group 2, and in 14% of group 3. There was no parallel between the frequency of Dupuytren's contracture and the severity of the liver involvement. Palmar erythema was noted in 34% of cases of group 1, 23% of cases of group 2, 12% of cases of group 3. Dupuytren's contracture has a genetic background, but its clinical expression is facilitated by metabolic causes, the most frequent being chronic alcoholism. Palmar erythema appears to be a sign of severe liver disease."}
{"id": "PMID:190685", "title": "[Alpha-1-antitrypsin deficiency. Phenotype study of 60 members of the same family].", "content": "In two brothers treated for severe pulmonary emphysema, was demonstrated an alpha-1-antitrypsin deficiency associated with a ZZ phenotype (Pi system). The authors carried out a genetic study of the family including 60 members spread over 4 generations. In all, were demonstrated 4 subjects of phenotype ZZ, 29 of phenotype MZ, 3 of phenotype MS ; one subject had a phenotype SZ and 23 members of this family had normal levels of alpha-1-antitrypsin and were of phenotype MM. The disease was transmitted in all cases as an autosomic codominant. The interest of a study of the phenotype in alpha-1-antitrypsin deficiency is emphasized together with the practical steps to be taken on discovery of a subject with the allele responsible for a reduction in serum levels of alpha-1-antitrypsin.", "contents": "[Alpha-1-antitrypsin deficiency. Phenotype study of 60 members of the same family]. In two brothers treated for severe pulmonary emphysema, was demonstrated an alpha-1-antitrypsin deficiency associated with a ZZ phenotype (Pi system). The authors carried out a genetic study of the family including 60 members spread over 4 generations. In all, were demonstrated 4 subjects of phenotype ZZ, 29 of phenotype MZ, 3 of phenotype MS ; one subject had a phenotype SZ and 23 members of this family had normal levels of alpha-1-antitrypsin and were of phenotype MM. The disease was transmitted in all cases as an autosomic codominant. The interest of a study of the phenotype in alpha-1-antitrypsin deficiency is emphasized together with the practical steps to be taken on discovery of a subject with the allele responsible for a reduction in serum levels of alpha-1-antitrypsin."}
{"id": "PMID:190686", "title": "[Human campylobacteriosis. Apropos of 6 cases].", "content": "Campylobacteriosis, first described as a disease of cattle where it is very common and causes sterility or abortion, appears to occur in man mainly in predisposed subjects with debility or some constitutional defect. The nature of the background should make one consider Campylobacter as pathogenic. Antibiotic treatment is necessary in all cases in order to avoid decompensation of the congenital disease. It is probable that Campylobacter infections are more common than the small number of reported cases would suggest. In the absence of characteristic clinical criteria, diagnosis depends on the results of bacteriological investigations. This should take into consideration the slowness of growth of the germ in culture and its nutrient and respiratory requirements. The diagnosis is mainly presumptive in the light of the history and clinical findings in order to ensure optimal conditions for isolation of the germ.", "contents": "[Human campylobacteriosis. Apropos of 6 cases]. Campylobacteriosis, first described as a disease of cattle where it is very common and causes sterility or abortion, appears to occur in man mainly in predisposed subjects with debility or some constitutional defect. The nature of the background should make one consider Campylobacter as pathogenic. Antibiotic treatment is necessary in all cases in order to avoid decompensation of the congenital disease. It is probable that Campylobacter infections are more common than the small number of reported cases would suggest. In the absence of characteristic clinical criteria, diagnosis depends on the results of bacteriological investigations. This should take into consideration the slowness of growth of the germ in culture and its nutrient and respiratory requirements. The diagnosis is mainly presumptive in the light of the history and clinical findings in order to ensure optimal conditions for isolation of the germ."}
{"id": "PMID:190687", "title": "[Headache and oral contraceptives (selective study of 159 cases)].", "content": "Based on a series of 159 cases of headache during oral contraception, the authors confirm the part plainly favouring and aggravating of oral contraceptives on headaches. They are dominated by the frequency of migraines and happen with predilection at the time of hormonal weaning. We deduct from this, that oral contraceptives generally aggravate or reveal a latent sensitivity to hormonal variations, especially clear with older women.", "contents": "[Headache and oral contraceptives (selective study of 159 cases)]. Based on a series of 159 cases of headache during oral contraception, the authors confirm the part plainly favouring and aggravating of oral contraceptives on headaches. They are dominated by the frequency of migraines and happen with predilection at the time of hormonal weaning. We deduct from this, that oral contraceptives generally aggravate or reveal a latent sensitivity to hormonal variations, especially clear with older women."}
{"id": "PMID:190692", "title": "[Cytomegalic inclusion disease].", "content": "Cytomegalic inclusion disease due to a virus of the herpes groups, which was first cultured in 1956 by Margaret Smith, is not only the disease of new-born known in France since 1952. Among the clinical pictures suggestive of this infection, one should include mononuclear syndromes with a negative Paul and Bunnell test which accompany cytomegalovirus viremia and a rise in specific antibodies.", "contents": "[Cytomegalic inclusion disease]. Cytomegalic inclusion disease due to a virus of the herpes groups, which was first cultured in 1956 by Margaret Smith, is not only the disease of new-born known in France since 1952. Among the clinical pictures suggestive of this infection, one should include mononuclear syndromes with a negative Paul and Bunnell test which accompany cytomegalovirus viremia and a rise in specific antibodies."}
{"id": "PMID:190693", "title": "[Mental disorders in the elderly].", "content": "In the psychopathology of old age, one should avoid a pessimistic attitude in therapeutics. A multidimensional approach will permit understanding of the psychological decompensation in old age, and the drawing up of coherent therapeutic plans which are often efficacious.", "contents": "[Mental disorders in the elderly]. In the psychopathology of old age, one should avoid a pessimistic attitude in therapeutics. A multidimensional approach will permit understanding of the psychological decompensation in old age, and the drawing up of coherent therapeutic plans which are often efficacious."}
{"id": "PMID:190694", "title": "[Pathological diagnosis of the superficial lymph nodes].", "content": "A cytological study, by needle puncture, of sub-cutaneous lymph nodes interpreted clinically as adenopathies, sometimes encounters difficulty which may lead to diagnostic errors. A few examples drawn from common practice, permit the authors to emphasize the interest of pathological examination by biopsy which shows the architecture of the tissues and the relations between the various cells and leads more easily to diagnosis of lesions which may be difficult to interpret.", "contents": "[Pathological diagnosis of the superficial lymph nodes]. A cytological study, by needle puncture, of sub-cutaneous lymph nodes interpreted clinically as adenopathies, sometimes encounters difficulty which may lead to diagnostic errors. A few examples drawn from common practice, permit the authors to emphasize the interest of pathological examination by biopsy which shows the architecture of the tissues and the relations between the various cells and leads more easily to diagnosis of lesions which may be difficult to interpret."}
{"id": "PMID:190695", "title": "[Echotomography in the surveillance of pregnancy].", "content": "The absence of use of ionising radiation contrary to the XRay scanner with computer, makes echotomography B, using ultrasound, a practically ideal method of supervision of pregnancy whether normal or pathological. The objections to its use, e.g. mechanical lesions detected on unicellular organisms in vitro, are not obvious in clinical medicine where the technique has now been in use for a sufficiently long time. However, one should not use this as a test of pregnancy but simply a method of supervision. During pregnancy either clinically or potentially pathological the use of this examination has been demonstrated whether one considers the pathology of the first trimester or that of the end of pregnancy.", "contents": "[Echotomography in the surveillance of pregnancy]. The absence of use of ionising radiation contrary to the XRay scanner with computer, makes echotomography B, using ultrasound, a practically ideal method of supervision of pregnancy whether normal or pathological. The objections to its use, e.g. mechanical lesions detected on unicellular organisms in vitro, are not obvious in clinical medicine where the technique has now been in use for a sufficiently long time. However, one should not use this as a test of pregnancy but simply a method of supervision. During pregnancy either clinically or potentially pathological the use of this examination has been demonstrated whether one considers the pathology of the first trimester or that of the end of pregnancy."}
{"id": "PMID:190696", "title": "[Prevention of infectious diseases of viral origin].", "content": "In France, smallpox and poliomyelitis have almost disappeared thanks to generalized vaccination, no case of small pox has been reported since 1975. 17 cases of poliomyelitis were reported in 1975. These two vaccinations remain compulsory. The prophylaxis of measles, which is a very common disease, is based on vaccination recommended for young children, particularly those living in groups. The frequency of severe forms of flu is reduced by vaccination which is advised in the elderly and in weak or exposed subjects. Rubella raises the problem of contamination of pregnant women. It is recommended to vaccinate young girls and also, after serological reactions, women who are professionally exposed to the disease. Epidemic virus hepatitis (virus A) is increasing in frequency, whereas transfusion hepatitis is becoming less common since the strict application of measures of prophylaxis. The spread of rabies, mainly in the fox, is worrying for public health workers. No case of human rabies has been noted in France. Preventive anti-rabic treatment is applied in the case of a patient bitten by a suspicious animal.", "contents": "[Prevention of infectious diseases of viral origin]. In France, smallpox and poliomyelitis have almost disappeared thanks to generalized vaccination, no case of small pox has been reported since 1975. 17 cases of poliomyelitis were reported in 1975. These two vaccinations remain compulsory. The prophylaxis of measles, which is a very common disease, is based on vaccination recommended for young children, particularly those living in groups. The frequency of severe forms of flu is reduced by vaccination which is advised in the elderly and in weak or exposed subjects. Rubella raises the problem of contamination of pregnant women. It is recommended to vaccinate young girls and also, after serological reactions, women who are professionally exposed to the disease. Epidemic virus hepatitis (virus A) is increasing in frequency, whereas transfusion hepatitis is becoming less common since the strict application of measures of prophylaxis. The spread of rabies, mainly in the fox, is worrying for public health workers. No case of human rabies has been noted in France. Preventive anti-rabic treatment is applied in the case of a patient bitten by a suspicious animal."}
{"id": "PMID:190697", "title": "[Prevention of anesthesia accidents].", "content": "All general anesthetics include a risk to life. The etiology and circumstances of complications with cardiac arrest are studied. Accent is placed on the frequency of fatal accidents for benign operations and on the poor prognosis of accidents with hypoxia. The prevention of accidents and their sequelae, such as encephalopathy, requires one to foresee and treat efficaciously as soon as possible cardiac arrest. To reach these objectives, efforts should be made on preparation of the patients, on the equipment and its maintenance, on the grouping of units where fatal accidents most frequently occur, on the creation of departments of anesthesia with re-awakening wards, on the training of medical and surgical teams with better supervision of young anesthetists.", "contents": "[Prevention of anesthesia accidents]. All general anesthetics include a risk to life. The etiology and circumstances of complications with cardiac arrest are studied. Accent is placed on the frequency of fatal accidents for benign operations and on the poor prognosis of accidents with hypoxia. The prevention of accidents and their sequelae, such as encephalopathy, requires one to foresee and treat efficaciously as soon as possible cardiac arrest. To reach these objectives, efforts should be made on preparation of the patients, on the equipment and its maintenance, on the grouping of units where fatal accidents most frequently occur, on the creation of departments of anesthesia with re-awakening wards, on the training of medical and surgical teams with better supervision of young anesthetists."}
{"id": "PMID:190698", "title": "[Skin reactions to topical agents].", "content": "The author desires to attract attention to the disadvantages of drugs for external use which are more and more widely used. The two main reactions observed are contact dermatitis and photosensitisation, but practically all skin lesions may be produced. She then rapidly recapitulates the various responsible agents insisting on dermo-corticoids and the precautions which should be taken in their use.", "contents": "[Skin reactions to topical agents]. The author desires to attract attention to the disadvantages of drugs for external use which are more and more widely used. The two main reactions observed are contact dermatitis and photosensitisation, but practically all skin lesions may be produced. She then rapidly recapitulates the various responsible agents insisting on dermo-corticoids and the precautions which should be taken in their use."}
{"id": "PMID:190699", "title": "[Drugs and hematologic toxicity].", "content": "Among the allergic accidents due to drugs, three clinical syndromes with brutal onset and acute evolution can occur. They are thrombocytopenic purpura, agranulocytosis and hemolytic anemia. An association of two or three syndromes is rare. The occurrence of these cytopenias resulting from an immuno-allergic process is due to a previous sensitization caused by a drug which, in the course of later treatment, would be able to induce an hematological accident in these sensitized subjects. These allergies always involve the formation of serum antibodies in sensitized subjects, the specific activity of which appears on the different cellular types in the presence of the drug responsible or of chemically related products. The specificity of allergic antibodies has been studied. Cross-reactions of these antibodies against products with a chemical formula close to that of the drug responsible have been observed. The physiopathological mechanisms of immuno-allergic sensitization are still uncertain. The most probable hypothesis involves the fixation of soluble complexes on to target cells. Further complement fixation would lead to a possible protection against these cytopenias.", "contents": "[Drugs and hematologic toxicity]. Among the allergic accidents due to drugs, three clinical syndromes with brutal onset and acute evolution can occur. They are thrombocytopenic purpura, agranulocytosis and hemolytic anemia. An association of two or three syndromes is rare. The occurrence of these cytopenias resulting from an immuno-allergic process is due to a previous sensitization caused by a drug which, in the course of later treatment, would be able to induce an hematological accident in these sensitized subjects. These allergies always involve the formation of serum antibodies in sensitized subjects, the specific activity of which appears on the different cellular types in the presence of the drug responsible or of chemically related products. The specificity of allergic antibodies has been studied. Cross-reactions of these antibodies against products with a chemical formula close to that of the drug responsible have been observed. The physiopathological mechanisms of immuno-allergic sensitization are still uncertain. The most probable hypothesis involves the fixation of soluble complexes on to target cells. Further complement fixation would lead to a possible protection against these cytopenias."}
{"id": "PMID:190700", "title": "[The present role of genetic counseling].", "content": "Any couple that has given birth to an abnormal child wants to know whether such an accident may reoccur. If wrongly reassured, they may see a new malformed child born. If they are wrongly advised against having a baby, they may use permanent sterilisation. Genetic advice is thus very important and should be carried out by a team which has available the necessary facilities for diagnosis and calculation of the precise risk.", "contents": "[The present role of genetic counseling]. Any couple that has given birth to an abnormal child wants to know whether such an accident may reoccur. If wrongly reassured, they may see a new malformed child born. If they are wrongly advised against having a baby, they may use permanent sterilisation. Genetic advice is thus very important and should be carried out by a team which has available the necessary facilities for diagnosis and calculation of the precise risk."}
{"id": "PMID:190701", "title": "[Treatment of the menopause].", "content": "The immediate complications of the menopause should be treated. These symptoms must be due to the menopause and the treatment should be without side effects. The object is above all to obtain a sense of well-being. More important than the immediate signs are the later trophic disorders, whether local or general. Thus a long term substitution treatment may be considered under strict supervision.", "contents": "[Treatment of the menopause]. The immediate complications of the menopause should be treated. These symptoms must be due to the menopause and the treatment should be without side effects. The object is above all to obtain a sense of well-being. More important than the immediate signs are the later trophic disorders, whether local or general. Thus a long term substitution treatment may be considered under strict supervision."}
{"id": "PMID:190702", "title": "Metastases in malignant childhood tumors-the role of \"adjuvant\" therapy and the utility of multidisciplinary treatment.", "content": "Patients with tumors which appear localized at diagnosis frequently develop metastases after primary definitive therapy. This suggests that occult (microscopic) dissemination of tumor has occurred prior to presentation. This is optimally treated early with chemotherapy after primary definitive treatment. The rationale for this approach is based on cytokinetic studies: micrometastases are more sensitive to anticancer agents thatn larger primary tumors from which they were derived and treatment administered when the tumor burden is at its nadir avoids the necessity to escalate doses and affect host tolerance. The application of these concepts to clinical practice has resulted in significant increases in survivals. Investigations to facilitate early detection of clinical metastases and the integrated use of multidisciplinary treatment for eradication of metastases are outlined.", "contents": "Metastases in malignant childhood tumors-the role of \"adjuvant\" therapy and the utility of multidisciplinary treatment. Patients with tumors which appear localized at diagnosis frequently develop metastases after primary definitive therapy. This suggests that occult (microscopic) dissemination of tumor has occurred prior to presentation. This is optimally treated early with chemotherapy after primary definitive treatment. The rationale for this approach is based on cytokinetic studies: micrometastases are more sensitive to anticancer agents thatn larger primary tumors from which they were derived and treatment administered when the tumor burden is at its nadir avoids the necessity to escalate doses and affect host tolerance. The application of these concepts to clinical practice has resulted in significant increases in survivals. Investigations to facilitate early detection of clinical metastases and the integrated use of multidisciplinary treatment for eradication of metastases are outlined."}
{"id": "PMID:190704", "title": "Follow-up of rape victims in a family practice setting.", "content": "Health care for rape victims traditionally has been crisis oriented, focused solely upon the victim, and provided either by a gynecologist or psychiatrist. A family practice health team, working in a county hospital, offered rape victims and their families crisis counseling in the emergency room, and follow-up care in a family practice clinic. Follow-up of victims markedly increased from 8% before initiation of the program to 86% afterward. Family members of more than half of the victims seen on follow-up received treatment. A wide range of health needs of both victims and their families, not identified in the emergency room, was identified on follow-up visits. In this way emergency care of the rape victim often became an entry point into the health care system. Rape must be viewed as a family's as well as victim's health problem, often demanding a broader service than can be offered by a gynecologist or psychiatrist alone.", "contents": "Follow-up of rape victims in a family practice setting. Health care for rape victims traditionally has been crisis oriented, focused solely upon the victim, and provided either by a gynecologist or psychiatrist. A family practice health team, working in a county hospital, offered rape victims and their families crisis counseling in the emergency room, and follow-up care in a family practice clinic. Follow-up of victims markedly increased from 8% before initiation of the program to 86% afterward. Family members of more than half of the victims seen on follow-up received treatment. A wide range of health needs of both victims and their families, not identified in the emergency room, was identified on follow-up visits. In this way emergency care of the rape victim often became an entry point into the health care system. Rape must be viewed as a family's as well as victim's health problem, often demanding a broader service than can be offered by a gynecologist or psychiatrist alone."}
{"id": "PMID:190705", "title": "Wilms' tumor in a multilocular cyst of the kidney (cystic Wilms' tumor).", "content": "A 2-year-old boy had a Wilms' tumor of the left kidney that appeared during physical examination as an abdominal mass and on gross examination as a multilocular cyst. Multilocular cyst of the kidney is a rare but distinctive congenital lesion. Its true biologic behavior is unknown. Although simple nephrectomy is sufficient for most lesions, more aggressive procedures are recommended for those lesions that contain Wilms' tumor (cystic Wilms' tumor).", "contents": "Wilms' tumor in a multilocular cyst of the kidney (cystic Wilms' tumor). A 2-year-old boy had a Wilms' tumor of the left kidney that appeared during physical examination as an abdominal mass and on gross examination as a multilocular cyst. Multilocular cyst of the kidney is a rare but distinctive congenital lesion. Its true biologic behavior is unknown. Although simple nephrectomy is sufficient for most lesions, more aggressive procedures are recommended for those lesions that contain Wilms' tumor (cystic Wilms' tumor)."}
{"id": "PMID:190707", "title": "Effects of diphenylhydantoin in 41 epileptics institutionalized since childhood.", "content": "Institutionalized epileptic patients on long-term anticonvulsant diphenylhydantoin (DPH) therapy were examined clinically. DPH plasma levels were unexpectedly high in 54% despite rather poor seizure control. No patient was free from side effects, which included gingival hypertrophy (90% of patients), increased alkaline phosphatase activity (55%), suggestion of a sensory peripheral neuropathy (34%), central nervous system (CNS) intoxication (22%), coarsened facial features (19%), tendency to bleed excessively (15%), hirsutism (12%), and mild megalocytic anemia (5%). CNS intoxication correlated with high plasma DPH levels, reports of deteriorating behavioral and motor performance, and the findings of nystagmus on vertical gaze or truncal ataxia, though not all patients with high plasma levels were clinically intoxicated. Alarming were the often disfiguring changes of gums and facial structures and the tendency to develop signs of vitamin D deficiency secondary to therapy. Hirsutism was rare in black patients. Plasma DPH level determinations are recommended as part of the management of mentally retarded epileptic patients but do not replace clinical acumen and skill.", "contents": "Effects of diphenylhydantoin in 41 epileptics institutionalized since childhood. Institutionalized epileptic patients on long-term anticonvulsant diphenylhydantoin (DPH) therapy were examined clinically. DPH plasma levels were unexpectedly high in 54% despite rather poor seizure control. No patient was free from side effects, which included gingival hypertrophy (90% of patients), increased alkaline phosphatase activity (55%), suggestion of a sensory peripheral neuropathy (34%), central nervous system (CNS) intoxication (22%), coarsened facial features (19%), tendency to bleed excessively (15%), hirsutism (12%), and mild megalocytic anemia (5%). CNS intoxication correlated with high plasma DPH levels, reports of deteriorating behavioral and motor performance, and the findings of nystagmus on vertical gaze or truncal ataxia, though not all patients with high plasma levels were clinically intoxicated. Alarming were the often disfiguring changes of gums and facial structures and the tendency to develop signs of vitamin D deficiency secondary to therapy. Hirsutism was rare in black patients. Plasma DPH level determinations are recommended as part of the management of mentally retarded epileptic patients but do not replace clinical acumen and skill."}
{"id": "PMID:190708", "title": "Ulnar nerve instability: ulnar nerve injury due to elbow flexion.", "content": "The term \"ulnar nerve instability\" describes the chronic conditions of subluxation and relocation of the ulnar nerve at the elbow with flexion and extension of the elbow, respectively. This condition is more common than generally thought. Recurrent subluxation of the nerve at the elbow results in a tractional and frictional neuritis. The nerve is vulnerable to trauma in its subluxed position, lying superficially on the medial humeral epicondyle. In certain cases of ulnar nerve instability associated with a tight overlying band bridging the heads of origin of the flexor carpi ulnaris, nerve injury can occur with flexion of the elbow. Thus, internal as well as external compressive factors as a cause of ulnar nerve neuropathy must be considered. Described is an elbow flexion test helpful in the diagnosis and prognosis of cases of ulnar nerve instability associated with the tight overlying band.", "contents": "Ulnar nerve instability: ulnar nerve injury due to elbow flexion. The term \"ulnar nerve instability\" describes the chronic conditions of subluxation and relocation of the ulnar nerve at the elbow with flexion and extension of the elbow, respectively. This condition is more common than generally thought. Recurrent subluxation of the nerve at the elbow results in a tractional and frictional neuritis. The nerve is vulnerable to trauma in its subluxed position, lying superficially on the medial humeral epicondyle. In certain cases of ulnar nerve instability associated with a tight overlying band bridging the heads of origin of the flexor carpi ulnaris, nerve injury can occur with flexion of the elbow. Thus, internal as well as external compressive factors as a cause of ulnar nerve neuropathy must be considered. Described is an elbow flexion test helpful in the diagnosis and prognosis of cases of ulnar nerve instability associated with the tight overlying band."}
{"id": "PMID:190709", "title": "Tendon xanthoma in type IV hyperlipoproteinemia.", "content": "A tendon xanthoma is reported in a patient with type IV hyperlipoproteinemia. This is an unusual situation not previously reported in the literature.", "contents": "Tendon xanthoma in type IV hyperlipoproteinemia. A tendon xanthoma is reported in a patient with type IV hyperlipoproteinemia. This is an unusual situation not previously reported in the literature."}
{"id": "PMID:190714", "title": "Chromosome analyses of two recently established human tumour cell lines derived from a carcinoma of the oesophagus and a primary liver tumour.", "content": "An oesophageal carcinoma cell line was karyotyped at passages 8,48,64 and 88. It showed a persistent loss of D group chromosomes and subtelocentric, acrocentric, dicentric and other markers were frequently present. During 80 passages the modal number declined from 60,5 to 54,09. The chromosome pattern of a hepatoma cell line was studied at passages 15/17 and 28. It showed a loss of D and G group chromosomes and the presence of various markers including a D/G fusion.", "contents": "Chromosome analyses of two recently established human tumour cell lines derived from a carcinoma of the oesophagus and a primary liver tumour. An oesophageal carcinoma cell line was karyotyped at passages 8,48,64 and 88. It showed a persistent loss of D group chromosomes and subtelocentric, acrocentric, dicentric and other markers were frequently present. During 80 passages the modal number declined from 60,5 to 54,09. The chromosome pattern of a hepatoma cell line was studied at passages 15/17 and 28. It showed a loss of D and G group chromosomes and the presence of various markers including a D/G fusion."}
{"id": "PMID:190716", "title": "Regional intra-arterial infusion of adriamycin in the treatment of cancer.", "content": "Forty patients with otherwise untreatable advanced carcinomas received arterial infusions of adriamycin. Significant responses were seen in five of nine tumors of the bladder, two of five hypernephromas, two of two islet cell tumors, three of five sarcomas and one of two metastatic tumors of the breast. One patient with advanced transitional cell carcinoma of the bladder had no tumor at the time of a subsequent resection. There were no responses seen in two oat cell tumors metastatic to the liver, one seminoma of the retroperitoneal space metastatic to the liver, one squamous cell tumor metastatic to the liver, one squamous cell of the vulva, one carcinoma of the cervix uteri and one cloacogenic carcinoma. these responses in advanced tumors are exciting. The use of this technique to reduce tumor bulk prior to operation, irradiation, adjuvant chemotherapy and immunotherapy may allow a significant breakthrough for such tumors as sarcomas, hypernephromas and transitional cell carcinomas of the bladder. Further studies will be pursued using this concept.", "contents": "Regional intra-arterial infusion of adriamycin in the treatment of cancer. Forty patients with otherwise untreatable advanced carcinomas received arterial infusions of adriamycin. Significant responses were seen in five of nine tumors of the bladder, two of five hypernephromas, two of two islet cell tumors, three of five sarcomas and one of two metastatic tumors of the breast. One patient with advanced transitional cell carcinoma of the bladder had no tumor at the time of a subsequent resection. There were no responses seen in two oat cell tumors metastatic to the liver, one seminoma of the retroperitoneal space metastatic to the liver, one squamous cell tumor metastatic to the liver, one squamous cell of the vulva, one carcinoma of the cervix uteri and one cloacogenic carcinoma. these responses in advanced tumors are exciting. The use of this technique to reduce tumor bulk prior to operation, irradiation, adjuvant chemotherapy and immunotherapy may allow a significant breakthrough for such tumors as sarcomas, hypernephromas and transitional cell carcinomas of the bladder. Further studies will be pursued using this concept."}
{"id": "PMID:190727", "title": "Acute silicoproteinosis.", "content": "A case of alveolar lipoproteinosis associated with silicosis is reported. A 58-year-old man had been exposed to silica for seven years and died three years after the onset of symptoms. Light microscopy of biopsy and necropsy material showed small silicotic nodules, silica particles, and alveolar lipoproteinosis, and ultrastructural studies were performed to define changes in alveolar epithelium and macrophages. The case provides a further example of alveolar lipoproteinosis developing as a response of the lung to injury by an external agent.", "contents": "Acute silicoproteinosis. A case of alveolar lipoproteinosis associated with silicosis is reported. A 58-year-old man had been exposed to silica for seven years and died three years after the onset of symptoms. Light microscopy of biopsy and necropsy material showed small silicotic nodules, silica particles, and alveolar lipoproteinosis, and ultrastructural studies were performed to define changes in alveolar epithelium and macrophages. The case provides a further example of alveolar lipoproteinosis developing as a response of the lung to injury by an external agent."}
{"id": "PMID:190730", "title": "[Tumors of the carotid body--diagnostic and therapeutic aspects (author's transl)].", "content": "The tumors of the carotid body are rare in frequency but still they give many problems in preoperative diagnosis and operative management. The pathological classification and estimation of dignity is still under discussion. Based on the experience of 5 patients we try to give a comprehensive listing of important facts and a classification for clinical use. In spite of the typical clinical signs which were described by Kocher and Fontaine the carotid body tumor is the most frequently mistaken tumor in the lateral region of the neck. If a tumor of this type is suspected a carotid arteriogram should be regularely performed. The arteriogram is the most important diagnostic procedure, and gives the final diagnosis in most cases. The therapeutic principle is the early total extirpation. In spite of the small rate of malignancy (under 10%) this challenge is based on the frequent observation of local spreading of the tumor. The excision of tumors of even large size is possible under consideration of special operative technics.", "contents": "[Tumors of the carotid body--diagnostic and therapeutic aspects (author's transl)]. The tumors of the carotid body are rare in frequency but still they give many problems in preoperative diagnosis and operative management. The pathological classification and estimation of dignity is still under discussion. Based on the experience of 5 patients we try to give a comprehensive listing of important facts and a classification for clinical use. In spite of the typical clinical signs which were described by Kocher and Fontaine the carotid body tumor is the most frequently mistaken tumor in the lateral region of the neck. If a tumor of this type is suspected a carotid arteriogram should be regularely performed. The arteriogram is the most important diagnostic procedure, and gives the final diagnosis in most cases. The therapeutic principle is the early total extirpation. In spite of the small rate of malignancy (under 10%) this challenge is based on the frequent observation of local spreading of the tumor. The excision of tumors of even large size is possible under consideration of special operative technics."}
{"id": "PMID:190731", "title": "Fine structure of the antennal receptors of the bed bug, Cimex lectularius L.", "content": "Sensilla on the antenna of the bed bug, Cimex lectularius, were studied with the scanning and transmission electron microscope. Those which display a tubular body in the dendrite ending are presumed to have a mechanoreceptor function (bristles of type A, flat plate of type B). Bristles of type A1 contain additional dendrites which terminate at the tip of the bristle and may be gustatory receptors.  Sensilla with pores in the hair wall are supposed to have an offactory, humidity and/or temperature receptor function (pegs and hairs of types C, D, E).  Hairs of type E contain receptors for the alarm pheromones of the bed bug.  Special attention has been paid to the pore structures and epicuticular layers of these sensilla. Possible differences in stimulus conduction are discussed between (i) sensilla with a simple wall and pores with pore tubules (types D and E) and (ii) the ribbed pegs (type C), which have a complex wall structure and spoke channels. The immersed cones of type F have a peculiar innervation, which has not been described previously. Two dendrites are held closely together by a third flat dendrite which wraps around them in the region of the outer segment. Coupling structures were found between the central dendrites, and between these and the third enveloping dendrite. Possible functions of this unique innervation are discussed. The dendrites innervating type D are grouped in three to eight bundles by multiple sheaths. The term thecogen cell is introduced to denote the innermost of the three sheath cells of a sensillum (the outer being the tormogen and the trichogen cell) which builds the dendrite sheath during ontogeny. Comparative morphometry revealed type-specific differences in the length and diameter of the dendrites. Some axons were found to lack any glial or perineurial sheath. Microorganisms were observed in the antennal tissue of several animals.", "contents": "Fine structure of the antennal receptors of the bed bug, Cimex lectularius L. Sensilla on the antenna of the bed bug, Cimex lectularius, were studied with the scanning and transmission electron microscope. Those which display a tubular body in the dendrite ending are presumed to have a mechanoreceptor function (bristles of type A, flat plate of type B). Bristles of type A1 contain additional dendrites which terminate at the tip of the bristle and may be gustatory receptors.  Sensilla with pores in the hair wall are supposed to have an offactory, humidity and/or temperature receptor function (pegs and hairs of types C, D, E).  Hairs of type E contain receptors for the alarm pheromones of the bed bug.  Special attention has been paid to the pore structures and epicuticular layers of these sensilla. Possible differences in stimulus conduction are discussed between (i) sensilla with a simple wall and pores with pore tubules (types D and E) and (ii) the ribbed pegs (type C), which have a complex wall structure and spoke channels. The immersed cones of type F have a peculiar innervation, which has not been described previously. Two dendrites are held closely together by a third flat dendrite which wraps around them in the region of the outer segment. Coupling structures were found between the central dendrites, and between these and the third enveloping dendrite. Possible functions of this unique innervation are discussed. The dendrites innervating type D are grouped in three to eight bundles by multiple sheaths. The term thecogen cell is introduced to denote the innermost of the three sheath cells of a sensillum (the outer being the tormogen and the trichogen cell) which builds the dendrite sheath during ontogeny. Comparative morphometry revealed type-specific differences in the length and diameter of the dendrites. Some axons were found to lack any glial or perineurial sheath. Microorganisms were observed in the antennal tissue of several animals."}
{"id": "PMID:190732", "title": "Epidermal cell development during the pupal-adult metamorphosis of Hyalophora cecropia.", "content": "To establish a base for studying the hormonal control of insect epidermal cell activity, the ultrastructure of abdominal epidermis was analyzed during the normal pupal-adult development of Hyalophora cecropia. Adjacent epidermal cells could be distinguished on the basis of organelle content and staining intensity, suggesting that this monolayer is not composed of a homogenous cell population. At the onset of adult development the form of the epidermal cell is transformed from that typical of a quiescent cell with free ribosomes and few mitochondria to one which is metabolically active and possesses numerous apical membrane microvilli, rough endoplasmic reticulum and numerous mitochondria. On about day 5 of pharate adult development the apical plasma membrane is no longer folded but becomes folded again several days later when cuticulin and endocuticle are deposited. On about day 7, giant autophagic vacuoles are discerned that may be important in cellular reprogramming. After adult ecdysis, the epidermal cells continue to deposit endocuticle.", "contents": "Epidermal cell development during the pupal-adult metamorphosis of Hyalophora cecropia. To establish a base for studying the hormonal control of insect epidermal cell activity, the ultrastructure of abdominal epidermis was analyzed during the normal pupal-adult development of Hyalophora cecropia. Adjacent epidermal cells could be distinguished on the basis of organelle content and staining intensity, suggesting that this monolayer is not composed of a homogenous cell population. At the onset of adult development the form of the epidermal cell is transformed from that typical of a quiescent cell with free ribosomes and few mitochondria to one which is metabolically active and possesses numerous apical membrane microvilli, rough endoplasmic reticulum and numerous mitochondria. On about day 5 of pharate adult development the apical plasma membrane is no longer folded but becomes folded again several days later when cuticulin and endocuticle are deposited. On about day 7, giant autophagic vacuoles are discerned that may be important in cellular reprogramming. After adult ecdysis, the epidermal cells continue to deposit endocuticle."}
{"id": "PMID:190733", "title": "Effects of ecdysone and juvenile hormone on epidermal cell development in Hyalophora cecropia.", "content": "Pupae of Hyalophora cecropia were injected with various doses of beta-ecdysone (molting hormone) or juvenile hormone and the epidermal cell ultrastructure was then studied with the electron microscope. The hormonal effects were rapidly manifested and appeared to be cell specific and dose dependent. The initial response to both hormones was an outward blebbing of the apical plasma membrane. Large doses of beta-ecdysone elicited both precocious cuticle deposition and premature autophagic vacuole formation. Juvenile hormone prevented the appearance of the autophagic vacuoles which normally preceded cell differentation into cells capable of adult synthesis. After prolonged exposure to juvenile hormone, there appeared to be an exaggerated separation of the epidermal cells at the basal region suggesting that the juvenile hormone may act at the membrane level.", "contents": "Effects of ecdysone and juvenile hormone on epidermal cell development in Hyalophora cecropia. Pupae of Hyalophora cecropia were injected with various doses of beta-ecdysone (molting hormone) or juvenile hormone and the epidermal cell ultrastructure was then studied with the electron microscope. The hormonal effects were rapidly manifested and appeared to be cell specific and dose dependent. The initial response to both hormones was an outward blebbing of the apical plasma membrane. Large doses of beta-ecdysone elicited both precocious cuticle deposition and premature autophagic vacuole formation. Juvenile hormone prevented the appearance of the autophagic vacuoles which normally preceded cell differentation into cells capable of adult synthesis. After prolonged exposure to juvenile hormone, there appeared to be an exaggerated separation of the epidermal cells at the basal region suggesting that the juvenile hormone may act at the membrane level."}
{"id": "PMID:190735", "title": "Calculation of intratumor temperature in a heated superficial tumor.", "content": "Measurements of intratumor temperature build-up in locally heated superificial tumor in the footpads of mice were analyzed. The intratumor temperature rise was found to consist of two slopes before the temperature reached a steady state. An empirical equation was developed, allowing a close estimate of the intratumor steady state temperature.", "contents": "Calculation of intratumor temperature in a heated superficial tumor. Measurements of intratumor temperature build-up in locally heated superificial tumor in the footpads of mice were analyzed. The intratumor temperature rise was found to consist of two slopes before the temperature reached a steady state. An empirical equation was developed, allowing a close estimate of the intratumor steady state temperature."}
{"id": "PMID:190738", "title": "In vitro metabolism of 3beta-hydroxy-, and 3beta,14alpha-dihydroxy-[3alpha-3H]-5beta-cholest-7-en-6-one by the prothoracic glands of Manduca sexta.", "content": "alpha-Ecdysone (2beta,3beta,14alpha,22R,25-pentahydroxy-5beta-cholest-7-en-6-one) has been identified as the metabolism product of 3beta,14alpha-dihydroxy-5beta-cholest-7-en-6-one in isolated prothoracic glands of the tobacco hornworm, Manduca sexta. In contrast, 3beta-hydroxy-5beta-cholest-7-en-6-one is metabolized to 14-deoxy-alpha-ecdysone and a variety of intermediates all lacking the 14-hydroxy group. The results suggest that either the normal precursor for the synthesis of alpha-ecdysone by prothoracic glands is a sterol more highly oxygenated than cholesterol or that hydroxylation of a minimally oxygenated precursor at C-14 must precede introduction of the C-6 ketone and/or delta7 bond. The data further suggest that several alternative hydroxylation routes may exist for the latter steps of alpha-ecdysone biosynthesis.", "contents": "In vitro metabolism of 3beta-hydroxy-, and 3beta,14alpha-dihydroxy-[3alpha-3H]-5beta-cholest-7-en-6-one by the prothoracic glands of Manduca sexta. alpha-Ecdysone (2beta,3beta,14alpha,22R,25-pentahydroxy-5beta-cholest-7-en-6-one) has been identified as the metabolism product of 3beta,14alpha-dihydroxy-5beta-cholest-7-en-6-one in isolated prothoracic glands of the tobacco hornworm, Manduca sexta. In contrast, 3beta-hydroxy-5beta-cholest-7-en-6-one is metabolized to 14-deoxy-alpha-ecdysone and a variety of intermediates all lacking the 14-hydroxy group. The results suggest that either the normal precursor for the synthesis of alpha-ecdysone by prothoracic glands is a sterol more highly oxygenated than cholesterol or that hydroxylation of a minimally oxygenated precursor at C-14 must precede introduction of the C-6 ketone and/or delta7 bond. The data further suggest that several alternative hydroxylation routes may exist for the latter steps of alpha-ecdysone biosynthesis."}
{"id": "PMID:190739", "title": "Estrogen metabolism in nonhuman primates. I. In vitro biosynthesis of estrogen glucosiduronates in rhesus monkey liver.", "content": "Estrone glucosiduronate, 17beta-estradiol-3-glucosiduronate, 17beta-estradiol-17-glucosiduronate and estriol-16alpha-glucosiduronate have been biosynthesized in substantial yield by incubation of radioactive estrone, 17beta-estradiol, estriol and uridine diphosphoglucosiduronic acid with rhesus monkey liver homogenates. The metabolites were characterized by chromatography on Celite and DEAE-Sephadex, enzyme hydrolysis, derivative formation and crystallization to constant specific activity. The percent conversion to 17beta-estradiol-17-glucosiduronate from 17beta-estradiol ranged between 56-71%; from estrone, the conversion was 49-54%. Other metabolites formed from estradiol were estrone glucosiduronate (12-21%) and 17beta-estradiol-3-glucosiduronate(5-12%). The same metabolites derived from estrone accounted for 18-28% and 10-14% respectively. After estriol incubation, more than 90% of the steroid was converted to estriol-16alpha-glucosiduronate with no detectable estriol-3-glucosiduronate. This report represents the first time that 17beta-estradiol-17-glucosiduronate has been reported as a metabolite in the rhesus monkey and this is the only known species which forms 17beta-estradiol-17-glucosiduronate as the predominant metabolite of either estrone or estradiol in vitro. Rhesus monkey liver is similar to the human and baboon in that it metabolizes estriol exclusively to estriol-16-glucosiduronate.", "contents": "Estrogen metabolism in nonhuman primates. I. In vitro biosynthesis of estrogen glucosiduronates in rhesus monkey liver. Estrone glucosiduronate, 17beta-estradiol-3-glucosiduronate, 17beta-estradiol-17-glucosiduronate and estriol-16alpha-glucosiduronate have been biosynthesized in substantial yield by incubation of radioactive estrone, 17beta-estradiol, estriol and uridine diphosphoglucosiduronic acid with rhesus monkey liver homogenates. The metabolites were characterized by chromatography on Celite and DEAE-Sephadex, enzyme hydrolysis, derivative formation and crystallization to constant specific activity. The percent conversion to 17beta-estradiol-17-glucosiduronate from 17beta-estradiol ranged between 56-71%; from estrone, the conversion was 49-54%. Other metabolites formed from estradiol were estrone glucosiduronate (12-21%) and 17beta-estradiol-3-glucosiduronate(5-12%). The same metabolites derived from estrone accounted for 18-28% and 10-14% respectively. After estriol incubation, more than 90% of the steroid was converted to estriol-16alpha-glucosiduronate with no detectable estriol-3-glucosiduronate. This report represents the first time that 17beta-estradiol-17-glucosiduronate has been reported as a metabolite in the rhesus monkey and this is the only known species which forms 17beta-estradiol-17-glucosiduronate as the predominant metabolite of either estrone or estradiol in vitro. Rhesus monkey liver is similar to the human and baboon in that it metabolizes estriol exclusively to estriol-16-glucosiduronate."}
{"id": "PMID:190743", "title": "Histopathology of carcinomas of the liver in mice ingesting dieldrin or aldrin.", "content": "C3HeB/Fe male and female mice, ingesting 10 ppm of the pesticides dieldrin or aldrin in the diet, developed highly significant incidences of carcinomas of the liver. The carcinomas varied from well differentiated to poorly differentiated and undifferentiated and were capable of metastasis.", "contents": "Histopathology of carcinomas of the liver in mice ingesting dieldrin or aldrin. C3HeB/Fe male and female mice, ingesting 10 ppm of the pesticides dieldrin or aldrin in the diet, developed highly significant incidences of carcinomas of the liver. The carcinomas varied from well differentiated to poorly differentiated and undifferentiated and were capable of metastasis."}
{"id": "PMID:190744", "title": "Analysis of 100 cases of Paget's disease of the breast.", "content": "Of 100 cases of Paget's disease of the breast admitted to the National Career Institute of Milan from 1940 to 1974, 91 were statistically evaluated. They were divided in two groups according to presence or absence of a palpable nodule. The results of surgical treatment in terms of 5 and 10 year survival rates were 59 and 44%, respectively, with a median survival of 9 years. For the two separate subgroups, those with a palpable nodule were 38 and 22% for 5 and 10 years, respectively, while those without a palpable nodule were 92 and 82% for 5 and 10 years, respectively. For the two groups the median survival was 3.6 and 16.4 years, respectively. The extent of surgery should be dependent on the presence of absence of palpable nodules under the nipple. For the two groups (with and without) extended radical mastectomy and the Patey-Dawson mastectomy are recommended.", "contents": "Analysis of 100 cases of Paget's disease of the breast. Of 100 cases of Paget's disease of the breast admitted to the National Career Institute of Milan from 1940 to 1974, 91 were statistically evaluated. They were divided in two groups according to presence or absence of a palpable nodule. The results of surgical treatment in terms of 5 and 10 year survival rates were 59 and 44%, respectively, with a median survival of 9 years. For the two separate subgroups, those with a palpable nodule were 38 and 22% for 5 and 10 years, respectively, while those without a palpable nodule were 92 and 82% for 5 and 10 years, respectively. For the two groups the median survival was 3.6 and 16.4 years, respectively. The extent of surgery should be dependent on the presence of absence of palpable nodules under the nipple. For the two groups (with and without) extended radical mastectomy and the Patey-Dawson mastectomy are recommended."}
{"id": "PMID:190748", "title": "Abnormal renal arteriography after renal trauma.", "content": "Angiograms following renal trauma in a ten-year-old girl were highly suggestive of renal neoplasm, especially Wilms' tumor. There are striking similarities between arteriograms after renal trauma and those showing neovascularity.", "contents": "Abnormal renal arteriography after renal trauma. Angiograms following renal trauma in a ten-year-old girl were highly suggestive of renal neoplasm, especially Wilms' tumor. There are striking similarities between arteriograms after renal trauma and those showing neovascularity."}
{"id": "PMID:190745", "title": "Syngeneic antitumor and antiembryo immunization affecting pregnancy in mice.", "content": "Groups of virgin BALB/c female were immunized against methylcholanthrene, SV40-induced or spontaneous syngeneic sarcoma cells or against syngeneic mitomycin-C blocked embryonic cells. Females were then mated to syngeneic males and observed for pregnancy rate and size of litters. To mimic the antiembryo immunization occurring during normal pregnancy, other experimental groups were added in which midgestational embryo fragments were kept in cell-impermeable diffusion chambers placed in the peritoneal cavity of virgin femals for 20 days, and removed before mating these females with syngeneic males. In all cases, antitumor and antiembryo immunization significantly reduced the number of successful pregnancies after the 1st mating while the second pregnancy appeared to be unaffected by the treatment. A significant reduction in the mean litter size was found, in mice immunized with embryonic tissues or with the SV40-induced sarcoma but not in those immunized with methylcholanthrene-induced or spontaneous tumors.", "contents": "Syngeneic antitumor and antiembryo immunization affecting pregnancy in mice. Groups of virgin BALB/c female were immunized against methylcholanthrene, SV40-induced or spontaneous syngeneic sarcoma cells or against syngeneic mitomycin-C blocked embryonic cells. Females were then mated to syngeneic males and observed for pregnancy rate and size of litters. To mimic the antiembryo immunization occurring during normal pregnancy, other experimental groups were added in which midgestational embryo fragments were kept in cell-impermeable diffusion chambers placed in the peritoneal cavity of virgin femals for 20 days, and removed before mating these females with syngeneic males. In all cases, antitumor and antiembryo immunization significantly reduced the number of successful pregnancies after the 1st mating while the second pregnancy appeared to be unaffected by the treatment. A significant reduction in the mean litter size was found, in mice immunized with embryonic tissues or with the SV40-induced sarcoma but not in those immunized with methylcholanthrene-induced or spontaneous tumors."}
{"id": "PMID:190749", "title": "Simultaneous nosocomial and community outbreak of epidemic keratoconjunctivitis with types 8 and 19 adenovirus.", "content": "In a simultaneous community and nosocomial (hospital-based) epidemic of keratoconjunctivitis lasting one year, 97 patients had clinical findings characteristic of EKC. Seventy-one percent of the cases were confirmed by laboratory tests including viral isolation, antibody response detected by complement fixation and hemagglutination inhibition tests, or immunofluorescent detection of adenovirus antigen in conjunctival scrapings. The community epidemic was a mixed adenovirus type 19 and type 8 outbreak. The nosocomial outbreak was due primarily to adenovirus type 8 (91%). The epidemiologic data of the nosocomial epidemic were representative of the population involved. The community outbreak was primarily in young individuals between 11 and 40 years of age. The secondary household attack rates were 20% and essentially were equal in both epidemics. The primary mode of spread in the nosocomial outbreak was by contamination of the examiner's fingers. In the community epidemic the mode of spread was believed to be close personal contact in a young and active age group.", "contents": "Simultaneous nosocomial and community outbreak of epidemic keratoconjunctivitis with types 8 and 19 adenovirus. In a simultaneous community and nosocomial (hospital-based) epidemic of keratoconjunctivitis lasting one year, 97 patients had clinical findings characteristic of EKC. Seventy-one percent of the cases were confirmed by laboratory tests including viral isolation, antibody response detected by complement fixation and hemagglutination inhibition tests, or immunofluorescent detection of adenovirus antigen in conjunctival scrapings. The community epidemic was a mixed adenovirus type 19 and type 8 outbreak. The nosocomial outbreak was due primarily to adenovirus type 8 (91%). The epidemiologic data of the nosocomial epidemic were representative of the population involved. The community outbreak was primarily in young individuals between 11 and 40 years of age. The secondary household attack rates were 20% and essentially were equal in both epidemics. The primary mode of spread in the nosocomial outbreak was by contamination of the examiner's fingers. In the community epidemic the mode of spread was believed to be close personal contact in a young and active age group."}
{"id": "PMID:190755", "title": "[Malignant kidney tumors in children].", "content": "The authors have examined 92 children with renal tumors. The treatment for Wilms tumor should be combined: preoperative irradiation, nephrectomy, postoperative irradiation. Late results were studied in 48 patients. 16 patients (33.3%) are living without the recurrence and metastases for over two years, including 4 over 5 years.", "contents": "[Malignant kidney tumors in children]. The authors have examined 92 children with renal tumors. The treatment for Wilms tumor should be combined: preoperative irradiation, nephrectomy, postoperative irradiation. Late results were studied in 48 patients. 16 patients (33.3%) are living without the recurrence and metastases for over two years, including 4 over 5 years."}
{"id": "PMID:190757", "title": "[Corticoid activation of infectious bovine rhinotracheitis virus--infectious pustular vulvovaginitis virus (IBR-IPV)].", "content": "The course of infection and IBR virus reactivation was studied in three experimentally infected weaned calves and three cows from naturally invaded herds. The animals were infected intranasally, intratracheally, and by contact. After 20, 41, and 105 days from primary infection, both in calves and in cows, dexametazon was applied in a series of six to seven intramuscular injections. The presence of the virus was examined in the nasal, conjunctival, vaginal and/or preputial secretions and in blood on diploid cells of calf kidneys and by the immunofluorescence method. In all infected calves, the disease took place with clinical signs of rhinotracheitis, mostly within the period of nine days. The second and third day after a temperature rise, the virus titre in nasal secretion reached the values ranging from 10(5) to 10(6.5). A markedly lower titre was obtained in the conjunctival secretion 10(0.5) to 10(3.5). In blood, the virus was found to be present on the first and fifth day from infection. After dexametazon application the calves and cows eliminated the virus mainly with the nasal secretion whose titre highly rose to the value of 10(3.5) to 10(47). In the conjunctival secretion the virus was present only irregularly and its quantities were very small. The greatest quantities of the virus were found in the nasal secretion on the sixth to the eight day from dexametazon application. The virus was not found in vaginal and preputial secretions. The levels of neutralizing antibodies were not affected by dexametazon in the calves; in cows they rose significantly from the titres of 1:2--1:4 to the titres of 1:16--1:32.", "contents": "[Corticoid activation of infectious bovine rhinotracheitis virus--infectious pustular vulvovaginitis virus (IBR-IPV)]. The course of infection and IBR virus reactivation was studied in three experimentally infected weaned calves and three cows from naturally invaded herds. The animals were infected intranasally, intratracheally, and by contact. After 20, 41, and 105 days from primary infection, both in calves and in cows, dexametazon was applied in a series of six to seven intramuscular injections. The presence of the virus was examined in the nasal, conjunctival, vaginal and/or preputial secretions and in blood on diploid cells of calf kidneys and by the immunofluorescence method. In all infected calves, the disease took place with clinical signs of rhinotracheitis, mostly within the period of nine days. The second and third day after a temperature rise, the virus titre in nasal secretion reached the values ranging from 10(5) to 10(6.5). A markedly lower titre was obtained in the conjunctival secretion 10(0.5) to 10(3.5). In blood, the virus was found to be present on the first and fifth day from infection. After dexametazon application the calves and cows eliminated the virus mainly with the nasal secretion whose titre highly rose to the value of 10(3.5) to 10(47). In the conjunctival secretion the virus was present only irregularly and its quantities were very small. The greatest quantities of the virus were found in the nasal secretion on the sixth to the eight day from dexametazon application. The virus was not found in vaginal and preputial secretions. The levels of neutralizing antibodies were not affected by dexametazon in the calves; in cows they rose significantly from the titres of 1:2--1:4 to the titres of 1:16--1:32."}
{"id": "PMID:190758", "title": "Clostridial myositis in cattle: bacteriology and gross pathology.", "content": "In a bacteriological study of 173 cases of clostridial myositis in cattle, Cl chauvoei either alone or with Cl septicum was demonstrated in 97 (56 %)min a further 62 (36%) cases Cl novyi was demonstrated either alone or with Cl septicum. On 11 (6%) occasions Cl septicum only was recovered, and on another three 1-7%) Cl sordelli only. The gross pathology of the lesions was correlated with the bacteriological findings, and prophylaxis in relation to the infections identified is discussed.", "contents": "Clostridial myositis in cattle: bacteriology and gross pathology. In a bacteriological study of 173 cases of clostridial myositis in cattle, Cl chauvoei either alone or with Cl septicum was demonstrated in 97 (56 %)min a further 62 (36%) cases Cl novyi was demonstrated either alone or with Cl septicum. On 11 (6%) occasions Cl septicum only was recovered, and on another three 1-7%) Cl sordelli only. The gross pathology of the lesions was correlated with the bacteriological findings, and prophylaxis in relation to the infections identified is discussed."}
{"id": "PMID:190762", "title": "Axonal and cellular alterations in the inner ear of rats treated with chlorphentermine or iprindole.", "content": "An electron-microscopic study was carried out on the inner ear of rats, which had been treated with the anorectic drug chlorphentermine and the antidepressant drug iprindole, two cationic amphiphilic compounds known to induce a generalized lipidosis. After chronic drug treatment the following vestibular and cochlear alterations were observed: a) numerous lamellated and crystalloid cytoplasmic inclusion bodies in various cell types, typical of drug-induced lipidosis; b) axonal balloonings predominantly affecting preterminal sensory endings which were filled with masses of coarse osmiophilic inclusions and autophagic vacuoles. With prolonged treatment degeneration of nerve fibers below the sensory epithelium was observed in increased numbers. Axonal changes are tentatively interpreted to result from drug-induced interference with certain catabolic processes involved in the normal degradation of axoplasmic constituents.", "contents": "Axonal and cellular alterations in the inner ear of rats treated with chlorphentermine or iprindole. An electron-microscopic study was carried out on the inner ear of rats, which had been treated with the anorectic drug chlorphentermine and the antidepressant drug iprindole, two cationic amphiphilic compounds known to induce a generalized lipidosis. After chronic drug treatment the following vestibular and cochlear alterations were observed: a) numerous lamellated and crystalloid cytoplasmic inclusion bodies in various cell types, typical of drug-induced lipidosis; b) axonal balloonings predominantly affecting preterminal sensory endings which were filled with masses of coarse osmiophilic inclusions and autophagic vacuoles. With prolonged treatment degeneration of nerve fibers below the sensory epithelium was observed in increased numbers. Axonal changes are tentatively interpreted to result from drug-induced interference with certain catabolic processes involved in the normal degradation of axoplasmic constituents."}
{"id": "PMID:190763", "title": "Influence of L-thyroxine upon enzymatic activity in  the renal tubular epithelium of the rat under normal conditions and in mercury-induced lesions. I. Histochemical studies of alkaline phosphatase, acid phosphatase, adenosine- tri-phosphatase and leucine-aminopeptidase.", "content": "HgC12-induced renal tubular lesions in the rat present histochemically with a transitory decrease of alkaline phosphatase, adenosinetriphosphatase (ATPase), and leucine-aminopeptidase activity. The toxic alterations of enzyme activity were more pronounced in the pars recta of the proximal tubule and in the loop of Henle, as compared with the tubulus contortus I. L-thyroxine treatment leads to an accelerated reversal of that enzymatic defect, followinga characteristic pattern, and to a differentiating increase of acid phosphatase and ATPase activity in certain parts of the normal renal tubule. The observations are discussed with reference to the specific mode of action of sublimate and l-thyroxine upon the tubular enzymes and to the well-known metabolic and functional influences of thyroid hormone on the kidney.", "contents": "Influence of L-thyroxine upon enzymatic activity in  the renal tubular epithelium of the rat under normal conditions and in mercury-induced lesions. I. Histochemical studies of alkaline phosphatase, acid phosphatase, adenosine- tri-phosphatase and leucine-aminopeptidase. HgC12-induced renal tubular lesions in the rat present histochemically with a transitory decrease of alkaline phosphatase, adenosinetriphosphatase (ATPase), and leucine-aminopeptidase activity. The toxic alterations of enzyme activity were more pronounced in the pars recta of the proximal tubule and in the loop of Henle, as compared with the tubulus contortus I. L-thyroxine treatment leads to an accelerated reversal of that enzymatic defect, followinga characteristic pattern, and to a differentiating increase of acid phosphatase and ATPase activity in certain parts of the normal renal tubule. The observations are discussed with reference to the specific mode of action of sublimate and l-thyroxine upon the tubular enzymes and to the well-known metabolic and functional influences of thyroid hormone on the kidney."}
{"id": "PMID:190794", "title": "[Synthesis of Rous sarcoma virus in mammalian embryonal tissue cultures].", "content": "In embryonal cells of mice and hamsters growing in vitro after Rous virus adsorption on them and long before the onset of cell transformation of the virus was detected in thr form closely associated with cells. After exposure of mammalian cells to actinomycin D or after lowering the temperature of their incubation up to +20 degrees C the cell associated virus was not revealed in embryonal cells. This evidences that the de novo synthesis of Rous virus but not the survival of the virus takes palce in the mentioned cells.", "contents": "[Synthesis of Rous sarcoma virus in mammalian embryonal tissue cultures]. In embryonal cells of mice and hamsters growing in vitro after Rous virus adsorption on them and long before the onset of cell transformation of the virus was detected in thr form closely associated with cells. After exposure of mammalian cells to actinomycin D or after lowering the temperature of their incubation up to +20 degrees C the cell associated virus was not revealed in embryonal cells. This evidences that the de novo synthesis of Rous virus but not the survival of the virus takes palce in the mentioned cells."}
{"id": "PMID:190795", "title": "[Kinetics of cell proliferation and growth of transplanted hepatoma in mice].", "content": "The authors compared the parameters of the growth and kinetics of the cell proliferation of five strains of transplantable mice hepatoma. By means of autoradiography and 3H-thymidine the curves of labeled mitoses and these of persistently labeled cells were obtained and analysed. Of all the mitotic cycle parameters: the time of G2 period and duration of phase S are mostly constant and not related with the rate of tumors growth. Hepatoma 46 is characterized by an extremely low intensity of cell production in relatively low their death rate. On the contrary, in hepatoma 48 possessing the same rate of growth the cell production was much more intensive, the rate of cell death being very high.", "contents": "[Kinetics of cell proliferation and growth of transplanted hepatoma in mice]. The authors compared the parameters of the growth and kinetics of the cell proliferation of five strains of transplantable mice hepatoma. By means of autoradiography and 3H-thymidine the curves of labeled mitoses and these of persistently labeled cells were obtained and analysed. Of all the mitotic cycle parameters: the time of G2 period and duration of phase S are mostly constant and not related with the rate of tumors growth. Hepatoma 46 is characterized by an extremely low intensity of cell production in relatively low their death rate. On the contrary, in hepatoma 48 possessing the same rate of growth the cell production was much more intensive, the rate of cell death being very high."}
{"id": "PMID:190797", "title": "Expression of red cell Bga antigen in children. Lack of correlation with previous EB virus infection.", "content": "The red cell Bga antigen and the presence of EB virus antibody were determined in a group of children of mixed ages. Evidence of previous infection with EB virus does not correlate with the degree of expression of the Bga antigen on red cells.", "contents": "Expression of red cell Bga antigen in children. Lack of correlation with previous EB virus infection. The red cell Bga antigen and the presence of EB virus antibody were determined in a group of children of mixed ages. Evidence of previous infection with EB virus does not correlate with the degree of expression of the Bga antigen on red cells."}
{"id": "PMID:190802", "title": "[Radiotherapy of Nephroblastoma (author's transl)].", "content": "The treatment methods for the differnt stages of the disease are discussed. The tumour is irradiated preoperatively. Intraoperatively, chemotherapy is commenced and, depending on the stage of the disease, radiotherapy is continued with chemotherapy. In stages III and IV and, if metastases occur, extended fields are irradiated, including the whole area of the body cavities. The abdomen is irradiated with 3000 rad, the lung with 1000-1200 rad and concomitant chemotherapy is given. Seven children were treated by us during 1969-1975 in conjunction with the Paediatric Department of Vienna University. All of them are still living. Severe radiation-induced side effects were observed in two of the cases.", "contents": "[Radiotherapy of Nephroblastoma (author's transl)]. The treatment methods for the differnt stages of the disease are discussed. The tumour is irradiated preoperatively. Intraoperatively, chemotherapy is commenced and, depending on the stage of the disease, radiotherapy is continued with chemotherapy. In stages III and IV and, if metastases occur, extended fields are irradiated, including the whole area of the body cavities. The abdomen is irradiated with 3000 rad, the lung with 1000-1200 rad and concomitant chemotherapy is given. Seven children were treated by us during 1969-1975 in conjunction with the Paediatric Department of Vienna University. All of them are still living. Severe radiation-induced side effects were observed in two of the cases."}
{"id": "PMID:190803", "title": "[Diagnostic, therapeutic and prognostic aspects of wilms' tumour (author's transl)].", "content": "Within the last 20 years 43 children with Wilms' tumour were seen at the Paediatric Departments of the University Hospitals of Graz, Innsbruck and Vienna. Case histories, clinical details and diagnostic procedures are discussed. Since 1969 19 out of 21 children were treated according to the modern atandard regimen (operation, irradiation and cytostatic therapy for 2 years except in infants with stage I). Since 1969 the survival rate has been higher (17 out of 21 children: 81%) than in the period 1956 to 1968 (7 out of 22 children: 31.8%), when only one child (in stage I) was treated according to current concepts. The better prognosis noted in young infants of this series, as in the literature was due to the earlier stage of the disease in these infants. A further improvement in the survival rate of children with Wilms' tumour should be achieved by earlier diagnosis, thereby ensuring operability, and by cytostatic therapy during the following 2 years. This will only be possible when there is closer cooperation between surgeon, radiotherapist and oncologist. It should be possible to lower the long-term therapeutic complication rate with even more stringent observation measures and with increasing expertise of all doctors concerned.", "contents": "[Diagnostic, therapeutic and prognostic aspects of wilms' tumour (author's transl)]. Within the last 20 years 43 children with Wilms' tumour were seen at the Paediatric Departments of the University Hospitals of Graz, Innsbruck and Vienna. Case histories, clinical details and diagnostic procedures are discussed. Since 1969 19 out of 21 children were treated according to the modern atandard regimen (operation, irradiation and cytostatic therapy for 2 years except in infants with stage I). Since 1969 the survival rate has been higher (17 out of 21 children: 81%) than in the period 1956 to 1968 (7 out of 22 children: 31.8%), when only one child (in stage I) was treated according to current concepts. The better prognosis noted in young infants of this series, as in the literature was due to the earlier stage of the disease in these infants. A further improvement in the survival rate of children with Wilms' tumour should be achieved by earlier diagnosis, thereby ensuring operability, and by cytostatic therapy during the following 2 years. This will only be possible when there is closer cooperation between surgeon, radiotherapist and oncologist. It should be possible to lower the long-term therapeutic complication rate with even more stringent observation measures and with increasing expertise of all doctors concerned."}
{"id": "PMID:190804", "title": "[Surgical treatment of wilms' tumour and neuroblastoma with particular reference to staging (author's transl)].", "content": "Combined surgical, irradiation and cytostatic therapy has considerably improved the outlook in cases of Wilms' tumour over the past years. Unfortunately the therapeautic results in neuroblastoma have not shown improvement to the same extent. Staging of the tumour is an essential basis for thee establishment of optimum therapeutic management and prognosis. Further improvement in results could be achieved with enhanced early diagnosis of these tumours and centralized treatment in centres with requisite specialist teams.", "contents": "[Surgical treatment of wilms' tumour and neuroblastoma with particular reference to staging (author's transl)]. Combined surgical, irradiation and cytostatic therapy has considerably improved the outlook in cases of Wilms' tumour over the past years. Unfortunately the therapeautic results in neuroblastoma have not shown improvement to the same extent. Staging of the tumour is an essential basis for thee establishment of optimum therapeutic management and prognosis. Further improvement in results could be achieved with enhanced early diagnosis of these tumours and centralized treatment in centres with requisite specialist teams."}
{"id": "PMID:190807", "title": "[The relation between the morphological stage of silicosis and the SiO2 content in hilar lymph nodes (author's transl)].", "content": "There is a positive relation with significant differences in mean values between the severity of silicosis of hilar lymph noeds and their SiO2 contents. The average SiO2 values in silicosis I amount to 2.03 g %; in silicosis II: 2.86 g%, and in silicosis III: 3.89 g%. The average values in exposed miners without silicosis (= 1.70 g%) show no significant differences in comparison with those of silicose I cases and those of nonexposed male persons (= 0.82 g%). The results justify the attempt of a morphological classification of the severity of silicosis in the hilar lymph nodes encouraging the use of chemical examinations of dust for the evaluation of pneumoconioses, for instance, in the material of mediastinoscopies.", "contents": "[The relation between the morphological stage of silicosis and the SiO2 content in hilar lymph nodes (author's transl)]. There is a positive relation with significant differences in mean values between the severity of silicosis of hilar lymph noeds and their SiO2 contents. The average SiO2 values in silicosis I amount to 2.03 g %; in silicosis II: 2.86 g%, and in silicosis III: 3.89 g%. The average values in exposed miners without silicosis (= 1.70 g%) show no significant differences in comparison with those of silicose I cases and those of nonexposed male persons (= 0.82 g%). The results justify the attempt of a morphological classification of the severity of silicosis in the hilar lymph nodes encouraging the use of chemical examinations of dust for the evaluation of pneumoconioses, for instance, in the material of mediastinoscopies."}
{"id": "PMID:190808", "title": "[The densitometric evaluation of lipoprotein electrophoresis on acetate foil and agar-agarose gel].", "content": "By means of cholesterol feeding on rabbits the change of the beta- and pre-beta-lipoprotein relations is observed by densitometric evaluation of lipoprotein electrophoreses on cellulose acetate foils and in agar-agarose gel. At the same time the changes of the cholesterol and triglyceride content of the sera are determined. The agar-agarose-gel electrophoreses prove to be more suitable for the densitometric evaluation compared with the electrophoreses on cellulose acetate foils, since they give more exact results. A reason for this is the worse demarcability of the pre-beta-lipoprotein proportion in the curves of the densitometre of acetate foils. The percental distributions of lipoprotein in patients of different types of HLP are determined and with the help of the results the evidence of the visual judgment of the lipoprotein electrophoreses is discussed.", "contents": "[The densitometric evaluation of lipoprotein electrophoresis on acetate foil and agar-agarose gel]. By means of cholesterol feeding on rabbits the change of the beta- and pre-beta-lipoprotein relations is observed by densitometric evaluation of lipoprotein electrophoreses on cellulose acetate foils and in agar-agarose gel. At the same time the changes of the cholesterol and triglyceride content of the sera are determined. The agar-agarose-gel electrophoreses prove to be more suitable for the densitometric evaluation compared with the electrophoreses on cellulose acetate foils, since they give more exact results. A reason for this is the worse demarcability of the pre-beta-lipoprotein proportion in the curves of the densitometre of acetate foils. The percental distributions of lipoprotein in patients of different types of HLP are determined and with the help of the results the evidence of the visual judgment of the lipoprotein electrophoreses is discussed."}
{"id": "PMID:190809", "title": "Quantity of antibody synthesized in a single cell during the primary immune response.", "content": "Following immunization of mice with SRBC the kinetics of antibody synthesis by individual immunocompetent cells during the primary immune response were investigated. The diameter of the average hemolytic plaque using a modified Jerne plaquing technique, was taken to be an estimate of the antibody production by a single cell. We found an increase, followed by a decrease, of the average plaque diameter during the primary immune response. The increase of average plaque diameters is probably due to the raised rate of synthesis of antibody molecules. This increase can be accelerated by adjuvants. The decrease late in the primary immune response could be explained by an internally regulated switch from IgM to IgG antibody synthesis. The results are consistent with the mathematical approach of HELLWIG (1,2).", "contents": "Quantity of antibody synthesized in a single cell during the primary immune response. Following immunization of mice with SRBC the kinetics of antibody synthesis by individual immunocompetent cells during the primary immune response were investigated. The diameter of the average hemolytic plaque using a modified Jerne plaquing technique, was taken to be an estimate of the antibody production by a single cell. We found an increase, followed by a decrease, of the average plaque diameter during the primary immune response. The increase of average plaque diameters is probably due to the raised rate of synthesis of antibody molecules. This increase can be accelerated by adjuvants. The decrease late in the primary immune response could be explained by an internally regulated switch from IgM to IgG antibody synthesis. The results are consistent with the mathematical approach of HELLWIG (1,2)."}
{"id": "PMID:190810", "title": "[Histological and histochemical studies of the stickleback Gasterosteus aculeatus L. kidney. III. Activity of various phosphatases depending on secretion].", "content": "1. The activity of alkaline phosphatase is intensely positive in proximal tubule I and II during the breeding season. In the kidney of secretion producing the enzyme is detectable as against to kidney of winter on the whole proximal tubule II. 2. In the kidney what is able to build a nest, concentration and size of acid phosphatase granules are very increasing in proximal tubule II. 3. The detection of unspecific esterase was negatively already. 4, The reaction of glucose-6-phosphatase is slightly demonstrable in cells of proximal segment of secretion producing what are enlarged fourfold. 5; From the varied reaction of acid and alkaline phosphatase we conclude that both are to set in relation to excretory activity, but not to process of synthesis in kidney of late-spring fish.", "contents": "[Histological and histochemical studies of the stickleback Gasterosteus aculeatus L. kidney. III. Activity of various phosphatases depending on secretion]. 1. The activity of alkaline phosphatase is intensely positive in proximal tubule I and II during the breeding season. In the kidney of secretion producing the enzyme is detectable as against to kidney of winter on the whole proximal tubule II. 2. In the kidney what is able to build a nest, concentration and size of acid phosphatase granules are very increasing in proximal tubule II. 3. The detection of unspecific esterase was negatively already. 4, The reaction of glucose-6-phosphatase is slightly demonstrable in cells of proximal segment of secretion producing what are enlarged fourfold. 5; From the varied reaction of acid and alkaline phosphatase we conclude that both are to set in relation to excretory activity, but not to process of synthesis in kidney of late-spring fish."}
{"id": "PMID:190813", "title": "Metastatic Wilms' tumor in the right atrium propagated through the inferior vena cava.", "content": "A patient with a rare case of cardiac tumor in the right atrium secondary to Wilms' tumor of the right kidney, underwent open heart surgery and removal of the mass was presented. This is the 10th. case of intracardiac tumor secondary to renal malignancy. Careful auscultation of the heart is necessary in patients with malignancy in the kidney to detect the possible right heart metastases through the inferior vena cava. Cardiac symptoms precede the renal manifestations in most cases. Malignant renal metastases to the heart should always be in mind in space occupying masses of the right heart chambers.", "contents": "Metastatic Wilms' tumor in the right atrium propagated through the inferior vena cava. A patient with a rare case of cardiac tumor in the right atrium secondary to Wilms' tumor of the right kidney, underwent open heart surgery and removal of the mass was presented. This is the 10th. case of intracardiac tumor secondary to renal malignancy. Careful auscultation of the heart is necessary in patients with malignancy in the kidney to detect the possible right heart metastases through the inferior vena cava. Cardiac symptoms precede the renal manifestations in most cases. Malignant renal metastases to the heart should always be in mind in space occupying masses of the right heart chambers."}
{"id": "PMID:190818", "title": "[Pathomorphologic studies of the endocrine cells in the gastrointestinal mucosa. Physiology, cytochemistry and ultrastructure (author's transl].", "content": "With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable electron density. According to most authors, they represent a distinct cell type and not just a variant of the G-cells. It may be very difficult, however, to separate certain forms of D1-cells from functionally altered G-cells. 5. The A-cell can be found in the gastric mucosa of certain animal species, where it has been demonstrated by immunocytochemistry with antisera to gut-glucagon. This cell type does not occur in the human gastric mucosa. 6...", "contents": "[Pathomorphologic studies of the endocrine cells in the gastrointestinal mucosa. Physiology, cytochemistry and ultrastructure (author's transl]. With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable electron density. According to most authors, they represent a distinct cell type and not just a variant of the G-cells. It may be very difficult, however, to separate certain forms of D1-cells from functionally altered G-cells. 5. The A-cell can be found in the gastric mucosa of certain animal species, where it has been demonstrated by immunocytochemistry with antisera to gut-glucagon. This cell type does not occur in the human gastric mucosa. 6..."}
{"id": "PMID:190821", "title": "[Clinical picture of prenatal virus infections].", "content": "Review about virus infections in pregnancy. The kind of damage, the incidence, the diagnostic possibilities and the management are discussed.", "contents": "[Clinical picture of prenatal virus infections]. Review about virus infections in pregnancy. The kind of damage, the incidence, the diagnostic possibilities and the management are discussed."}
{"id": "PMID:190822", "title": "[Sulphated glycosaminoglycans as virus inhibitors. 4th communication: clinical aspects of zoster with the proposal of a new treatment (author's transl)].", "content": "On the base of plaque inhibition tests in at least three virus-host-systems and successful treatment of mice with experimentally induced yellow fever encephalitis a well known sulphated glycosaminoglycan (GAGPS) \"L5\" was used as therapeutic agent in cases of zoster infection in man. The material was applied as 1% solution in water continuously on lint and rewettet for several days until nearly complete healing was achieved. The clinical course of 18 patients of former years (12 women, 6 men) was compared with 26 cases (19 women, 7 men) treated additionally with the new substance. All of them were carefully observed in the Rudolf-Virchow-Hospital in Berlin. Besides of registrating data as age and sex of the patients and the seasonal distribution of cases the course of illness was analyzed. The mean duration before admission to the hopsital was 4,9 days in the control group and 7,2 days in the L5-patients. Signs of organ diseases possibly acting as trigger mechanism for the remanifestation of the zoster were nearly twice in number in L5 cases than in the controls. Despite of this unfavorable stiutation the main parameters showed a clear tendency to return earlier to normal values in the GAGPS group. The fever was shortened. The blood lymphocytes normalized better with mean absolute values of 2400 in the L5-group and 3029 per m(3) in the control cases. The fall of the cell number in the liquor cerebrospinalis was more rapidly in the GAGPS treatment. The mean stay in the hospital was 33,2 days in L5 cases and 44,6 days in control patients respectively in the main group of age between 60 and 80 years. One death in the GAGPS group corresponded to four in the control group.  In the local skin area the edema disappeared rapidly with beginning of treatment. Confluent vesicles flattened within 24 to 48 hours and no further efflorescences were seen. Pain diminished in few days. The good results justify continued trials.", "contents": "[Sulphated glycosaminoglycans as virus inhibitors. 4th communication: clinical aspects of zoster with the proposal of a new treatment (author's transl)]. On the base of plaque inhibition tests in at least three virus-host-systems and successful treatment of mice with experimentally induced yellow fever encephalitis a well known sulphated glycosaminoglycan (GAGPS) \"L5\" was used as therapeutic agent in cases of zoster infection in man. The material was applied as 1% solution in water continuously on lint and rewettet for several days until nearly complete healing was achieved. The clinical course of 18 patients of former years (12 women, 6 men) was compared with 26 cases (19 women, 7 men) treated additionally with the new substance. All of them were carefully observed in the Rudolf-Virchow-Hospital in Berlin. Besides of registrating data as age and sex of the patients and the seasonal distribution of cases the course of illness was analyzed. The mean duration before admission to the hopsital was 4,9 days in the control group and 7,2 days in the L5-patients. Signs of organ diseases possibly acting as trigger mechanism for the remanifestation of the zoster were nearly twice in number in L5 cases than in the controls. Despite of this unfavorable stiutation the main parameters showed a clear tendency to return earlier to normal values in the GAGPS group. The fever was shortened. The blood lymphocytes normalized better with mean absolute values of 2400 in the L5-group and 3029 per m(3) in the control cases. The fall of the cell number in the liquor cerebrospinalis was more rapidly in the GAGPS treatment. The mean stay in the hospital was 33,2 days in L5 cases and 44,6 days in control patients respectively in the main group of age between 60 and 80 years. One death in the GAGPS group corresponded to four in the control group.  In the local skin area the edema disappeared rapidly with beginning of treatment. Confluent vesicles flattened within 24 to 48 hours and no further efflorescences were seen. Pain diminished in few days. The good results justify continued trials."}
{"id": "PMID:190823", "title": "Typing of Group A streptococci from an urban area (K\u00f6ln) in West Germany.", "content": "Two-hundred and twenty strains of Streptococcus pyogenes (group A streptococcus) from the urban area of K\u00f6ln, West Germany have been typed by M precipitin and T agglutination tests. Determination of streptococcal nicotinamide adenine dinucleotide glycohydrolase (NADase) production and the serum opacity reaction (SOR) have also been performed. 65.5% of the isolates could be typed by the M precipitin reaction. 92.1% of the remaining strains could be identified by their T protein antigens and could be further subdivided according to their NADase/SOR pattern. Most of the M typable strains originated from upper respiratory tract infections (including scarlet fever), whereas the majority of the M nontypable streptocci had been isolated from skin, wound, and other non-respiratory sites.", "contents": "Typing of Group A streptococci from an urban area (K\u00f6ln) in West Germany. Two-hundred and twenty strains of Streptococcus pyogenes (group A streptococcus) from the urban area of K\u00f6ln, West Germany have been typed by M precipitin and T agglutination tests. Determination of streptococcal nicotinamide adenine dinucleotide glycohydrolase (NADase) production and the serum opacity reaction (SOR) have also been performed. 65.5% of the isolates could be typed by the M precipitin reaction. 92.1% of the remaining strains could be identified by their T protein antigens and could be further subdivided according to their NADase/SOR pattern. Most of the M typable strains originated from upper respiratory tract infections (including scarlet fever), whereas the majority of the M nontypable streptocci had been isolated from skin, wound, and other non-respiratory sites."}
{"id": "PMID:190819", "title": "Primary carcinoma of the liver in Zambia.", "content": "A review of liver biopsies over a three year period revealed 166 cases of carcinoma of the liver. Hepatocellular carcinoma constituted the commonest malignant tumour in male Zambians. The different histologic sub-types were studied and compared wth a study of liver cell cancer in Uganda. Trabecular carcinoma was the commonest histological type. A significant association of hepatocellular carcinoma with macronodular cirrhosis was noted.", "contents": "Primary carcinoma of the liver in Zambia. A review of liver biopsies over a three year period revealed 166 cases of carcinoma of the liver. Hepatocellular carcinoma constituted the commonest malignant tumour in male Zambians. The different histologic sub-types were studied and compared wth a study of liver cell cancer in Uganda. Trabecular carcinoma was the commonest histological type. A significant association of hepatocellular carcinoma with macronodular cirrhosis was noted."}
{"id": "PMID:190824", "title": "[Blood pressure and pulse frequency during oral intake of cadmium sulfide in animal experiment (author's transl)].", "content": "Female wistar rats were given cadmium sulfide in various concentrations in their chow (26 mg CdS/kg feed and 52 mg tcdS/kg feed). After a three month trial no significant changes in blood pressure could be seen. The pulse frequencies showed the falling tendency with increasing weight, as already seen in healthy rats.", "contents": "[Blood pressure and pulse frequency during oral intake of cadmium sulfide in animal experiment (author's transl)]. Female wistar rats were given cadmium sulfide in various concentrations in their chow (26 mg CdS/kg feed and 52 mg tcdS/kg feed). After a three month trial no significant changes in blood pressure could be seen. The pulse frequencies showed the falling tendency with increasing weight, as already seen in healthy rats."}
{"id": "PMID:190825", "title": "[Microbial resistance to formaldehyde. I. Comparative quantitative studies in some selected species of vegetative bacteria, bacterial spores, fungi, bacteriophages and viruses].", "content": "The resistence of different microorganisms to formaldehyde was determined. As test objects served gram-negative and gram-positive vegetative germs (Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella paratyphi-B, Staphylococcus aureus, Streptococcus faecalis), bacterial spores (Bacillus cereus, Bacillus pumilus, Bacillus stearothermophilus, Bacillus subtilis), fungi (Aspergillus niger, Candida albicans), bacteriophages (Escherichia coli phages, T1, T2, T3), and viruses (adenovirus, poliomyelitis virus, vaccinia virus). For the studies, suspensions of germs were exposed at identical temperature (20 degrees C) and pH (7.0). The microbicidal effect of formaldehyde was measured by the decrease of the proportion of germs capable of multiplication in the suspension (lg (N/N0); where: N0 equals initial number of germs capable of multiplication; N equals number of germs capable of multiplication after exposure to formaldehyde). For all germs the dependence of the microbicidal effect on the concentration of formaldehyde was determined. In all experiments, the duration of exposure was two hours. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Salmonella paratyphi-B were found to be more susceptible than Staphylococcus aureus (vf. Fig. 1 A). The strains of Pseudomonas aeruginosa used were widely varying as to their susceptibility. To obtain equal microbicidal effects, concentrations of formaldehyde almost three times as high had to be used for the most resistant strain than were necessary for the most susceptible strain of Pseudomonas aeruginosa. All strains of Klebsiella pneumoniae examined were found to have an identical resistence to formaldehyde. Streptococcus faecalis was even more resistant to formaldehyde than Staphylococcus aureus. In the case of Streptococcus faecalis, a concentration of formaldehyde about three times as high had to be used to obtain microbicidal effects of identical magnitude. For the killing of Candida albicans cells concentrations of formaldehyde not higher than those needed for the killing of vegetative gram-negative bacteria were necessary. The conidia of Aspergillus niger were found to be more resistant than the cells of Candida albicans but did not require any higher concentrations than for the killing of Staphylococcus aureus (see Fig. 1 B). In the case of bacterial spores, a special phenomenon was observed. If the spores had been exposed to a temperature of 80 and 95 degrees C, respectively (depending on the species involved) for one or two hours following exposure to formaldehyde, a considerably higher number of spores was found to be capable of germination and colony formation than without such treatment (heat activation: cf. Fig. 2A and Fig. 2B). The spores of Bacillus cereus had only a relatively low resistance to formaldehyde. To reduce the proportion of the spores capable of colony formation to 1/10000, a 2.9% formaldehyde concentration was necessary without heat activation and one of 10.8% with heat activation...", "contents": "[Microbial resistance to formaldehyde. I. Comparative quantitative studies in some selected species of vegetative bacteria, bacterial spores, fungi, bacteriophages and viruses]. The resistence of different microorganisms to formaldehyde was determined. As test objects served gram-negative and gram-positive vegetative germs (Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella paratyphi-B, Staphylococcus aureus, Streptococcus faecalis), bacterial spores (Bacillus cereus, Bacillus pumilus, Bacillus stearothermophilus, Bacillus subtilis), fungi (Aspergillus niger, Candida albicans), bacteriophages (Escherichia coli phages, T1, T2, T3), and viruses (adenovirus, poliomyelitis virus, vaccinia virus). For the studies, suspensions of germs were exposed at identical temperature (20 degrees C) and pH (7.0). The microbicidal effect of formaldehyde was measured by the decrease of the proportion of germs capable of multiplication in the suspension (lg (N/N0); where: N0 equals initial number of germs capable of multiplication; N equals number of germs capable of multiplication after exposure to formaldehyde). For all germs the dependence of the microbicidal effect on the concentration of formaldehyde was determined. In all experiments, the duration of exposure was two hours. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Salmonella paratyphi-B were found to be more susceptible than Staphylococcus aureus (vf. Fig. 1 A). The strains of Pseudomonas aeruginosa used were widely varying as to their susceptibility. To obtain equal microbicidal effects, concentrations of formaldehyde almost three times as high had to be used for the most resistant strain than were necessary for the most susceptible strain of Pseudomonas aeruginosa. All strains of Klebsiella pneumoniae examined were found to have an identical resistence to formaldehyde. Streptococcus faecalis was even more resistant to formaldehyde than Staphylococcus aureus. In the case of Streptococcus faecalis, a concentration of formaldehyde about three times as high had to be used to obtain microbicidal effects of identical magnitude. For the killing of Candida albicans cells concentrations of formaldehyde not higher than those needed for the killing of vegetative gram-negative bacteria were necessary. The conidia of Aspergillus niger were found to be more resistant than the cells of Candida albicans but did not require any higher concentrations than for the killing of Staphylococcus aureus (see Fig. 1 B). In the case of bacterial spores, a special phenomenon was observed. If the spores had been exposed to a temperature of 80 and 95 degrees C, respectively (depending on the species involved) for one or two hours following exposure to formaldehyde, a considerably higher number of spores was found to be capable of germination and colony formation than without such treatment (heat activation: cf. Fig. 2A and Fig. 2B). The spores of Bacillus cereus had only a relatively low resistance to formaldehyde. To reduce the proportion of the spores capable of colony formation to 1/10000, a 2.9% formaldehyde concentration was necessary without heat activation and one of 10.8% with heat activation..."}
{"id": "PMID:190829", "title": "[Rational method of producing sera with high titers of virus neutralizing antibodies].", "content": "A possibility of obtaining the diagnostic specific sera with a high titre against the poliovirus, type I, was studied experimentally. Five different immunization schemes by the same antigen were tested in parallel experiments. A method of the viral antigen (both of the concentrated and of the unconcentrated) mixed with complete Freund's adjuvant injection into the popliteal lymph nodes with the subsequent single reimmunization proved to be most effective. In this way it was possible to obtain type-specific sera with a high titre (1:20 000--1:40 000) in the course of five weeks.", "contents": "[Rational method of producing sera with high titers of virus neutralizing antibodies]. A possibility of obtaining the diagnostic specific sera with a high titre against the poliovirus, type I, was studied experimentally. Five different immunization schemes by the same antigen were tested in parallel experiments. A method of the viral antigen (both of the concentrated and of the unconcentrated) mixed with complete Freund's adjuvant injection into the popliteal lymph nodes with the subsequent single reimmunization proved to be most effective. In this way it was possible to obtain type-specific sera with a high titre (1:20 000--1:40 000) in the course of five weeks."}
{"id": "PMID:190830", "title": "[Isolation and purification of a preparation possessing leukocytosis-stimulating properties from pertussis bacteria].", "content": "A homogeneous protein LSF-2 preparation was extracted from the cultural fluid of Bordetella pertussis strains of the 1.0.3 serological type by means of precipitation with ammonium sulphate and electrofocussing; this preparation proved to produce a marked leukocytosis-stimulating and a weak toxic action of delayed type in experiments on animals. Intraperitoneal administration of 5 mug of the LSF-2 preparation caused a rise of leukocytosis in mice to 100,000 cells per 1 mm3, a delay in the gain in weight beginning from the 3rd day of the administration and a late death of the animals in 5% of cases. The LSF-2 preparation protected the mice in infection with a virulent pertussis strain No. 18323 in the amount of from 12 to 91%, depending on the immunizing dose; its ImD50 was equal to 2.0 -2.4 mug of protein. The results of investigations carried out permitted to assess the role of this substance in the formation of specific immunity in pertussis infection.", "contents": "[Isolation and purification of a preparation possessing leukocytosis-stimulating properties from pertussis bacteria]. A homogeneous protein LSF-2 preparation was extracted from the cultural fluid of Bordetella pertussis strains of the 1.0.3 serological type by means of precipitation with ammonium sulphate and electrofocussing; this preparation proved to produce a marked leukocytosis-stimulating and a weak toxic action of delayed type in experiments on animals. Intraperitoneal administration of 5 mug of the LSF-2 preparation caused a rise of leukocytosis in mice to 100,000 cells per 1 mm3, a delay in the gain in weight beginning from the 3rd day of the administration and a late death of the animals in 5% of cases. The LSF-2 preparation protected the mice in infection with a virulent pertussis strain No. 18323 in the amount of from 12 to 91%, depending on the immunizing dose; its ImD50 was equal to 2.0 -2.4 mug of protein. The results of investigations carried out permitted to assess the role of this substance in the formation of specific immunity in pertussis infection."}
{"id": "PMID:190831", "title": "[Purification of the toxoids of Cl. Perfringens and Cl. pedematiens using silicagel].", "content": "A possibility was shown of purification of the concentrated toxoids of the Cl. perfringens and Cl. oedematiens species in examination of KSK-2, KSK-2,5; MCA-2 silicagels. The specific activity of the preparations obtained and the yield approached the analogous indices obtained in stratification of Sephadex G-75. The effect of preliminary silicagel treatment and also of the nature of buffer solutions on the efficacy of the process of purification of the gangrenous toxoids was established.", "contents": "[Purification of the toxoids of Cl. Perfringens and Cl. pedematiens using silicagel]. A possibility was shown of purification of the concentrated toxoids of the Cl. perfringens and Cl. oedematiens species in examination of KSK-2, KSK-2,5; MCA-2 silicagels. The specific activity of the preparations obtained and the yield approached the analogous indices obtained in stratification of Sephadex G-75. The effect of preliminary silicagel treatment and also of the nature of buffer solutions on the efficacy of the process of purification of the gangrenous toxoids was established."}
{"id": "PMID:190827", "title": "[Influence of spontaneous arousal during hibernation of the activity of the pituitary-adrenal system in the suslik Citellus erythrogenis].", "content": "Periodic spontaneous arousals of ground squirrels during hibernation are accompanied by activation of the hypophyseal-adrenal system. However, together with a 3-fold increase in hypophyseal ACTH and 2-fold increase in 11-oxycorticosterioid secretion by the adrenals, more than 2-fold decrease in the content of these hormones in the peripheral blood was observed. The latter may result from the increased corticosteroid metabolism. It is suggested that spontaneous arousals may act as a synchronizer of endogenous rhythm of the activity of the hypophyseal-adrenal system during winter hibernation.", "contents": "[Influence of spontaneous arousal during hibernation of the activity of the pituitary-adrenal system in the suslik Citellus erythrogenis]. Periodic spontaneous arousals of ground squirrels during hibernation are accompanied by activation of the hypophyseal-adrenal system. However, together with a 3-fold increase in hypophyseal ACTH and 2-fold increase in 11-oxycorticosterioid secretion by the adrenals, more than 2-fold decrease in the content of these hormones in the peripheral blood was observed. The latter may result from the increased corticosteroid metabolism. It is suggested that spontaneous arousals may act as a synchronizer of endogenous rhythm of the activity of the hypophyseal-adrenal system during winter hibernation."}
{"id": "PMID:190832", "title": "[Clinico-electrophysiologic studies of experimental herpetic encephalitis].", "content": "Studies on animals demonstrated that in experimental herpetic encephalitis there is a diffuse retardation of background bioelectric brain activity and a proxysmal activity of 2 types: peek complex-slow waves 3 per 1 sec. and periodical paroxysmal complexes. There is also an increase of latent periods, duration and amplitudes of visual evoked potentials. Electrophysiological data correlate with the clinical picture of herpetic encephalitis and pathomorphological changes in the CNS. The obtained data are discussed with consideration bor the theory of neuron epileptization and hemodynamical disturbances.", "contents": "[Clinico-electrophysiologic studies of experimental herpetic encephalitis]. Studies on animals demonstrated that in experimental herpetic encephalitis there is a diffuse retardation of background bioelectric brain activity and a proxysmal activity of 2 types: peek complex-slow waves 3 per 1 sec. and periodical paroxysmal complexes. There is also an increase of latent periods, duration and amplitudes of visual evoked potentials. Electrophysiological data correlate with the clinical picture of herpetic encephalitis and pathomorphological changes in the CNS. The obtained data are discussed with consideration bor the theory of neuron epileptization and hemodynamical disturbances."}
{"id": "PMID:190833", "title": "[Clinical and biochemical heterogenicity of phenylketonuria in adults].", "content": "The authors carried out a clinical and biochemical investigation of 23 phenylketonuric patients at the age of 17--49 who were not treated specifically. The clinical examination showed that behavioural reactions, attacks of psychomotor excitation, neurological status, presence or absence of strokes and other symptoms of the disease were heterogenous. It has been established that disturbances of acid, protein, adipose and carbohydrate metabolism have different degrees of expressiveness. The clinical manifestation of the disease is conditioned by heterogeneity of monolocus mutations of the PAH gene.", "contents": "[Clinical and biochemical heterogenicity of phenylketonuria in adults]. The authors carried out a clinical and biochemical investigation of 23 phenylketonuric patients at the age of 17--49 who were not treated specifically. The clinical examination showed that behavioural reactions, attacks of psychomotor excitation, neurological status, presence or absence of strokes and other symptoms of the disease were heterogenous. It has been established that disturbances of acid, protein, adipose and carbohydrate metabolism have different degrees of expressiveness. The clinical manifestation of the disease is conditioned by heterogeneity of monolocus mutations of the PAH gene."}
{"id": "PMID:190835", "title": "[Functions of the adrenal cortex in patients with supratentorial brain tumors and their prognostic value for surgical intervention].", "content": "The functional activity of the adrenal cortex was studied pre- and postoperatively in patients with pituitary adenomas, craiopharyngiomas and supratentorial meningiomas. With the hypothalamus function preserved, the patients developed varying degrees of stress-responses in the postoperative period. Severe morphological injuries to the hypothalamus make the normal response to surgical trauma impossible. With some functional centers preserved, the diencephalo-catabolic syndrome develops. Severe injuries of the diencephalon, with its adaptative function completely lost, result in the development of the diencephalic areactive syndrome.", "contents": "[Functions of the adrenal cortex in patients with supratentorial brain tumors and their prognostic value for surgical intervention]. The functional activity of the adrenal cortex was studied pre- and postoperatively in patients with pituitary adenomas, craiopharyngiomas and supratentorial meningiomas. With the hypothalamus function preserved, the patients developed varying degrees of stress-responses in the postoperative period. Severe morphological injuries to the hypothalamus make the normal response to surgical trauma impossible. With some functional centers preserved, the diencephalo-catabolic syndrome develops. Severe injuries of the diencephalon, with its adaptative function completely lost, result in the development of the diencephalic areactive syndrome."}
{"id": "PMID:190836", "title": "Effect of vertebrate hormones on the cyclic AMP level in Tetrahymena.", "content": "Epinephrine, insulin, glucagon and theophylline produced a significant increase in the cAMP level of Tetrahymena, while the enhancing effect of TSH was not significant. The experimental results suggest that Tetrahymena possesses receptors for hormones of higher animals, but has no receptor for the nonsense hormone TSH. The cAMP enhancing effect shown by many hormones of higher animals irrespective of their different functions indicates that apart from the general mediator action of cAMP, some special mediation is also taking place.", "contents": "Effect of vertebrate hormones on the cyclic AMP level in Tetrahymena. Epinephrine, insulin, glucagon and theophylline produced a significant increase in the cAMP level of Tetrahymena, while the enhancing effect of TSH was not significant. The experimental results suggest that Tetrahymena possesses receptors for hormones of higher animals, but has no receptor for the nonsense hormone TSH. The cAMP enhancing effect shown by many hormones of higher animals irrespective of their different functions indicates that apart from the general mediator action of cAMP, some special mediation is also taking place."}
{"id": "PMID:190838", "title": "Biological activities of ACTH-analogues varied in the active site.", "content": "The steroidogenic and lipolytic activities of corticotrophin-(1-24)-tetracosapeptide and [Lys17,18]corticotrophin-(1-18)-octadecapeptide amide were compared with those of corresponding analogues substituted in position 8 with norarginine and homoarginine, and in position 9 with phenylalanine and pentamethylphenylalanine. The norarginine containing analogues demonstrated a rewarding activity, although they were generally somewhat less active than the homoarginine containing compounds. This confirms the previous conclusions concerning the indispensability of arginine as a guanidinium derivate. The analogues in which phenylalanine was a substitute for tryptophan, constituted partial agonists with a low activity in steroidogenesis and lipolysis but a rather high melanophore stimulating activity. Insertion of the permethylated derivative of phenylalanine in this position, which ensures the presence of an aminoacyl residue with the full electron donor properties of tryptophan, destroyed the low steroidogenic and lipolytic activity, but increased the MSH-activity about 2-fold.", "contents": "Biological activities of ACTH-analogues varied in the active site. The steroidogenic and lipolytic activities of corticotrophin-(1-24)-tetracosapeptide and [Lys17,18]corticotrophin-(1-18)-octadecapeptide amide were compared with those of corresponding analogues substituted in position 8 with norarginine and homoarginine, and in position 9 with phenylalanine and pentamethylphenylalanine. The norarginine containing analogues demonstrated a rewarding activity, although they were generally somewhat less active than the homoarginine containing compounds. This confirms the previous conclusions concerning the indispensability of arginine as a guanidinium derivate. The analogues in which phenylalanine was a substitute for tryptophan, constituted partial agonists with a low activity in steroidogenesis and lipolysis but a rather high melanophore stimulating activity. Insertion of the permethylated derivative of phenylalanine in this position, which ensures the presence of an aminoacyl residue with the full electron donor properties of tryptophan, destroyed the low steroidogenic and lipolytic activity, but increased the MSH-activity about 2-fold."}
{"id": "PMID:190839", "title": "Stimulation of longitudinal bone growth by hypophyseal hormones in the hypophysectomized rat.", "content": "The stimulating effect of different pituitary hormones on longitudinal bone growth was determined with tetracycline as intravital marker in hypophysectomized rats. Growth hormone was found to be the most effective growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating activity. TSH exerts its effect via the production of thyroxine, whereas the growth stimulation by prolactin seems to be a direct effect of this hormone, similar to the effect of growth hormone. The LH, FSH, ACTH, MSH, vasopressin and oxytocin preparations did not stimulate longitudinal bone growth.", "contents": "Stimulation of longitudinal bone growth by hypophyseal hormones in the hypophysectomized rat. The stimulating effect of different pituitary hormones on longitudinal bone growth was determined with tetracycline as intravital marker in hypophysectomized rats. Growth hormone was found to be the most effective growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating activity. TSH exerts its effect via the production of thyroxine, whereas the growth stimulation by prolactin seems to be a direct effect of this hormone, similar to the effect of growth hormone. The LH, FSH, ACTH, MSH, vasopressin and oxytocin preparations did not stimulate longitudinal bone growth."}
{"id": "PMID:190840", "title": "Altered responsiveness to hypophysiotrophic hormones of perifused rat pituitary tumours.", "content": "Since growth hormone (GH) and prolactin (Prl) secretion by human pituitary tumours is often influenced by the hypophysiotrophic hormones thyrotrophin-releasing hormone (TRH) and somatostatin (SRIF), we have examined the responses of several transplantable rat pituitary tumours to these substances in a perifusion apparatus. The MStT/W15 tumour did not alter its secretion of GH and Prl in response to TRH, SRIF, or a partially purified porcine hypothalamic extract containing GH-releasing activity; normal rat pituitaries show clear responses to each of these substances. Theophylline and dibutyryl cyclic AMP each provoked increased GH and Prl release from the tumour. A second specimen of the MStT/W15 tumour and a specimen of the MStT/W5 tumour behaved in a manner identical to the original MStT/W15, showing no response to TRH or SRIF, but releasing both GH and Prl when theophylline or dibutyryl cyclic AMP was given. The MtT/F4 tumour increased its secretion of GH in response to TRH, 10 mug/ml, and theophylline, but no effect was seen with lower concentrations of TRH or with SRIF; Prl secretion by the F4 tumour was increased by theophylline, but TRH and SRIF had no effect. The autonomy demonstrated in these experimental tumours may be due to a loss of specific hypophysiotrophic hormone receptors or of secretory activating mechanisms.", "contents": "Altered responsiveness to hypophysiotrophic hormones of perifused rat pituitary tumours. Since growth hormone (GH) and prolactin (Prl) secretion by human pituitary tumours is often influenced by the hypophysiotrophic hormones thyrotrophin-releasing hormone (TRH) and somatostatin (SRIF), we have examined the responses of several transplantable rat pituitary tumours to these substances in a perifusion apparatus. The MStT/W15 tumour did not alter its secretion of GH and Prl in response to TRH, SRIF, or a partially purified porcine hypothalamic extract containing GH-releasing activity; normal rat pituitaries show clear responses to each of these substances. Theophylline and dibutyryl cyclic AMP each provoked increased GH and Prl release from the tumour. A second specimen of the MStT/W15 tumour and a specimen of the MStT/W5 tumour behaved in a manner identical to the original MStT/W15, showing no response to TRH or SRIF, but releasing both GH and Prl when theophylline or dibutyryl cyclic AMP was given. The MtT/F4 tumour increased its secretion of GH in response to TRH, 10 mug/ml, and theophylline, but no effect was seen with lower concentrations of TRH or with SRIF; Prl secretion by the F4 tumour was increased by theophylline, but TRH and SRIF had no effect. The autonomy demonstrated in these experimental tumours may be due to a loss of specific hypophysiotrophic hormone receptors or of secretory activating mechanisms."}
{"id": "PMID:190841", "title": "The effect of treatment of hyper- and hypothyroidism on urinary excretion of cyclic adenosine 3',5'-monophosphate.", "content": "The urinary excretion of cyclic adenosine 3',5'-monophosphate (cyclic AMP) was examined in patients with hyperthyroidism and primary hypothyroidism, before treatment and at least six months later on return to euthyroid status. Urinary cyclic AMP excretion was significantly greater in the hyperthyroid group than in the hypothyroid group both in the basal state (P less than 0.01) and the ambulant state (P less than 0.001). In ambulant hyperthyroid patients absolute urinary cyclic AMP excretion (mumol/24 h) was significantly greater (P less than 0.05) prior to treatment than on return to euthyroid status. In the hypothyroid group no significant change occurred after treatment with 1-thyroxine (P greater than 0.05). The mechanism of changes in urinary cyclic AMP excretion in thyroid disease are discussed.", "contents": "The effect of treatment of hyper- and hypothyroidism on urinary excretion of cyclic adenosine 3',5'-monophosphate. The urinary excretion of cyclic adenosine 3',5'-monophosphate (cyclic AMP) was examined in patients with hyperthyroidism and primary hypothyroidism, before treatment and at least six months later on return to euthyroid status. Urinary cyclic AMP excretion was significantly greater in the hyperthyroid group than in the hypothyroid group both in the basal state (P less than 0.01) and the ambulant state (P less than 0.001). In ambulant hyperthyroid patients absolute urinary cyclic AMP excretion (mumol/24 h) was significantly greater (P less than 0.05) prior to treatment than on return to euthyroid status. In the hypothyroid group no significant change occurred after treatment with 1-thyroxine (P greater than 0.05). The mechanism of changes in urinary cyclic AMP excretion in thyroid disease are discussed."}
{"id": "PMID:190842", "title": "Studies of a thyroid hormone and androgen dependent protein in rat liver cytosol.", "content": "Sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis of the liver cytosol of euthyroid male rats revealed a prominent band (molecular weight, 26 000 daltons), designated Protein II, which was virtually absent in the cytosol of hypothyroid animals. Injection of 500 mug triiodothyronine (T3) per 100 g body weight resulted in a maximal increase in the level of Protein II, reaching 90% of the euthyroidal level 3 days after hormone administration. Concomitant studies with the liver mitochondrial enzyme alpha-glycerophosphate dehydrogenase (alpha-GPD) indicated that this T3 dose also resulted in a maximal enzyme response in this time period. Since we have estimated that 500 mug of T3 will saturate nearly all nuclear T3 binding sites, these results support the concept that the synthesis of both proteins is limited by nuclear binding. Protein II was absent in the liver cytosol of female rats but could be induced in ovariectomized female rats by androgens. Treatment of male rats with oestradiol resulted in disappearance of Protein II. Since administration of testosterone to hypothyroid male rats caused only a minimal increase in the amount of Protein II, the absence of the protein in hypothyroid animals was not due to androgen deficiency. Similarities in the molecular weight and the response to hormonal manipulation of Protein II and of the urinary alpha2uglobulin, previously reported by Roy (1973) raise the possibility that these proteins are the same. The high concentration of Protein II in male rat cytosol and the relative ease in its identification by SDS polyacrylamide gel electrophoresis make it a potentially useful model protein for the study of thyroid hormone action at the cellular level.", "contents": "Studies of a thyroid hormone and androgen dependent protein in rat liver cytosol. Sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis of the liver cytosol of euthyroid male rats revealed a prominent band (molecular weight, 26 000 daltons), designated Protein II, which was virtually absent in the cytosol of hypothyroid animals. Injection of 500 mug triiodothyronine (T3) per 100 g body weight resulted in a maximal increase in the level of Protein II, reaching 90% of the euthyroidal level 3 days after hormone administration. Concomitant studies with the liver mitochondrial enzyme alpha-glycerophosphate dehydrogenase (alpha-GPD) indicated that this T3 dose also resulted in a maximal enzyme response in this time period. Since we have estimated that 500 mug of T3 will saturate nearly all nuclear T3 binding sites, these results support the concept that the synthesis of both proteins is limited by nuclear binding. Protein II was absent in the liver cytosol of female rats but could be induced in ovariectomized female rats by androgens. Treatment of male rats with oestradiol resulted in disappearance of Protein II. Since administration of testosterone to hypothyroid male rats caused only a minimal increase in the amount of Protein II, the absence of the protein in hypothyroid animals was not due to androgen deficiency. Similarities in the molecular weight and the response to hormonal manipulation of Protein II and of the urinary alpha2uglobulin, previously reported by Roy (1973) raise the possibility that these proteins are the same. The high concentration of Protein II in male rat cytosol and the relative ease in its identification by SDS polyacrylamide gel electrophoresis make it a potentially useful model protein for the study of thyroid hormone action at the cellular level."}
{"id": "PMID:190843", "title": "Oestrogen formation from C19 precursors in human choriocarcinoma in culture.", "content": "A cloned cell line of human choriocarcinoma was evaluated as a model of human placental oestrogen production. Oestrone formation from dehydroepiandrosterone (D), D-sulphate (DS) or 4-androstenedione (A) was less than or equal to 5% of oestradiol-17beta (Oe2) formation. Oe2 formation from D and A was similar (100-150 pmole/h/10(7) cells); that from DS was 10 times less. Omitting serum from the medium increased Oe2 yield from DS 4-fold; addition of albumin restored these yields to control values (P greater than 0.05, t-test), presumably by binding DS. N6,O2'-dibutyryl-adenosine 3',5'-cyclic monophosphoric acid and theophylline treatment for 72 h stimulated (P less than 0.01) Oe2 formation from D (36%), DS (66%) and A (183%). In intact cells, sulphatase activity, Oe2 formation from D and Oe2 formation from DS equalled those in homogenates (P greater than 0.05) but Oe2 formation from D was greater than that from DS in both systems (P less than 0.001), indicating a deficiency of sulphatase relative to subsequent enzymes of oestrogen synthesis. Steroids, at concentrations previously shown to inhibit placental sulphatase or 3beta-hydroxysteroid dehydrogenase, did not inhibit choriocarcinoma enzymes. Except for its relative sulphatase deficiency and insusceptibility of oestrogen synthesizing enzymes to steroid inhibitors, choriocarcinoma appears to be a useful model of placental oestrogen synthesis.", "contents": "Oestrogen formation from C19 precursors in human choriocarcinoma in culture. A cloned cell line of human choriocarcinoma was evaluated as a model of human placental oestrogen production. Oestrone formation from dehydroepiandrosterone (D), D-sulphate (DS) or 4-androstenedione (A) was less than or equal to 5% of oestradiol-17beta (Oe2) formation. Oe2 formation from D and A was similar (100-150 pmole/h/10(7) cells); that from DS was 10 times less. Omitting serum from the medium increased Oe2 yield from DS 4-fold; addition of albumin restored these yields to control values (P greater than 0.05, t-test), presumably by binding DS. N6,O2'-dibutyryl-adenosine 3',5'-cyclic monophosphoric acid and theophylline treatment for 72 h stimulated (P less than 0.01) Oe2 formation from D (36%), DS (66%) and A (183%). In intact cells, sulphatase activity, Oe2 formation from D and Oe2 formation from DS equalled those in homogenates (P greater than 0.05) but Oe2 formation from D was greater than that from DS in both systems (P less than 0.001), indicating a deficiency of sulphatase relative to subsequent enzymes of oestrogen synthesis. Steroids, at concentrations previously shown to inhibit placental sulphatase or 3beta-hydroxysteroid dehydrogenase, did not inhibit choriocarcinoma enzymes. Except for its relative sulphatase deficiency and insusceptibility of oestrogen synthesizing enzymes to steroid inhibitors, choriocarcinoma appears to be a useful model of placental oestrogen synthesis."}
{"id": "PMID:190844", "title": "Inherited erythrocyte pyruvate kinase deficiency: Studies on 15 members of two related families.", "content": "The case of a haemolytic non-spherocytic anaemia with pyruvate kinase (PK) deficiency is reported. The investigation concerns two families with a low level of PK. In the propositus and in the members of his family we have also examined the behaviour of some enzymes and the concentration of red cell metabolites. We confirm the heterogeneity of the manifestation and agree that anaemias due to PK deficiency are complex forms in which the enzyme defect is only one of the symptoms.", "contents": "Inherited erythrocyte pyruvate kinase deficiency: Studies on 15 members of two related families. The case of a haemolytic non-spherocytic anaemia with pyruvate kinase (PK) deficiency is reported. The investigation concerns two families with a low level of PK. In the propositus and in the members of his family we have also examined the behaviour of some enzymes and the concentration of red cell metabolites. We confirm the heterogeneity of the manifestation and agree that anaemias due to PK deficiency are complex forms in which the enzyme defect is only one of the symptoms."}
{"id": "PMID:190846", "title": "Fine structure of myomedulloblastoma.", "content": "Electronmicroscopic studies in a case of myomedulloblastoma support the concept that the medulloblastoma and the myoblastoma component of the tumor derive drom different cell lines. The myoblastoma component shows bundles of myogenic elements, whereby quite undifferentiated cells lacking myofilaments are tightly attached to differentiated elements having well organized myofilaments. These bundles are encompassed by a common basement membrane, and their cells are joined by junctions, helping the identification of the undifferentiated elements. No comparable structures were seen in the medulloblastoma component. The fine structure of the myoblastoma is reminiscent of aspects of normal fetal development of skeletal muscle.", "contents": "Fine structure of myomedulloblastoma. Electronmicroscopic studies in a case of myomedulloblastoma support the concept that the medulloblastoma and the myoblastoma component of the tumor derive drom different cell lines. The myoblastoma component shows bundles of myogenic elements, whereby quite undifferentiated cells lacking myofilaments are tightly attached to differentiated elements having well organized myofilaments. These bundles are encompassed by a common basement membrane, and their cells are joined by junctions, helping the identification of the undifferentiated elements. No comparable structures were seen in the medulloblastoma component. The fine structure of the myoblastoma is reminiscent of aspects of normal fetal development of skeletal muscle."}
{"id": "PMID:190847", "title": "The target phenomenon in rat muscle following tenotomy and neurotomy. A comparative light microscopic and histochemical study.", "content": "Target fibers were checked at regular intervals in two groups of rat gastrocnemius muscle namely after tenotomy and neurotomy. The highest amount of target fibres was observed during the first week following tenotomy and around the seventh week, when the muscle became again functional by spontaneous union of the tendon. The target phenomenon was restricted to the type II fibres. It appeared also in the early stage of re-innervation, 5 weeks following neurotomy and remained present subsequently in a transitional zone between denervated and re-innervated muscle fibres and was restricted to the type I muscle fibres. The target phenomenon was not the only histochemical alteration observed following tenotomy and neurotomy. This experimental study allowed to determinate more precisely the causal factors of the target phenomenon.", "contents": "The target phenomenon in rat muscle following tenotomy and neurotomy. A comparative light microscopic and histochemical study. Target fibers were checked at regular intervals in two groups of rat gastrocnemius muscle namely after tenotomy and neurotomy. The highest amount of target fibres was observed during the first week following tenotomy and around the seventh week, when the muscle became again functional by spontaneous union of the tendon. The target phenomenon was restricted to the type II fibres. It appeared also in the early stage of re-innervation, 5 weeks following neurotomy and remained present subsequently in a transitional zone between denervated and re-innervated muscle fibres and was restricted to the type I muscle fibres. The target phenomenon was not the only histochemical alteration observed following tenotomy and neurotomy. This experimental study allowed to determinate more precisely the causal factors of the target phenomenon."}
{"id": "PMID:190848", "title": "The incidence of ultrastructural abnormalities in the cortex of two retarded human brains (Down's syndrome).", "content": "In a quantitative electronmicroscopic study, autopsy samples from the frontal and temporal lobes of two severely defective mongoloid brains were examined for the presence of abnormalities in the ultrastructure of the cerebral cortex. Particular attention was paid to the occurrence of atypical neuronal and glial inclusions similar to those which occur in small numbers (1 in 5000 mu2 of cortex) in neurologically normal brain (Rees, 1975). An area of 3.6 x 10(5) mu2 of cortex was examined from each brain. Within the cortical parenchyma, there was no gliosis, neuronal death or areas of degeneration.  Atypical neuronal and glial inclusions were observed in both of the retarded brains, but they did not occur in substantially different numbers from normal brains. There were no inclusions or structural abnormalities peculiar to the retarded brains. Thus, in these two defective brains, it has not been possible to demonstrate any specific abnormalities in the ultrastructure of the cortex.", "contents": "The incidence of ultrastructural abnormalities in the cortex of two retarded human brains (Down's syndrome). In a quantitative electronmicroscopic study, autopsy samples from the frontal and temporal lobes of two severely defective mongoloid brains were examined for the presence of abnormalities in the ultrastructure of the cerebral cortex. Particular attention was paid to the occurrence of atypical neuronal and glial inclusions similar to those which occur in small numbers (1 in 5000 mu2 of cortex) in neurologically normal brain (Rees, 1975). An area of 3.6 x 10(5) mu2 of cortex was examined from each brain. Within the cortical parenchyma, there was no gliosis, neuronal death or areas of degeneration.  Atypical neuronal and glial inclusions were observed in both of the retarded brains, but they did not occur in substantially different numbers from normal brains. There were no inclusions or structural abnormalities peculiar to the retarded brains. Thus, in these two defective brains, it has not been possible to demonstrate any specific abnormalities in the ultrastructure of the cortex."}
{"id": "PMID:190849", "title": "Corpora amylacea in the peripheral nerve axons.", "content": "Deposits similar to corpora amylacea were observed by electron microscopy within myelinated axons in the peripheral nerves in a case of familial spastic paralysis. Ultrastructurally the deposits consisted of randomly interlacing short filaments which were closely related to glycogen granules present in the periphery of the deposits. A possible relationship between the filamentous structures and glycogen granules is discussed. The significance of this inclusion and of related bodies is also discussed.", "contents": "Corpora amylacea in the peripheral nerve axons. Deposits similar to corpora amylacea were observed by electron microscopy within myelinated axons in the peripheral nerves in a case of familial spastic paralysis. Ultrastructurally the deposits consisted of randomly interlacing short filaments which were closely related to glycogen granules present in the periphery of the deposits. A possible relationship between the filamentous structures and glycogen granules is discussed. The significance of this inclusion and of related bodies is also discussed."}
{"id": "PMID:190850", "title": "Pituitary growth hormone cell adenoma with cytoplasmic tubular aggregates in the capillary endothelium.", "content": "Electron microscopy revealed the presence of cytoplasmic tubular aggregates in the capillary endothelium of a sparsely granulated growth hormone cell adenoma removed surgically from a 25-year-old female patient with acromegaly. To our knowledge, this is the second publication describing these structures in hypophysial growth hormone cell adenomas.", "contents": "Pituitary growth hormone cell adenoma with cytoplasmic tubular aggregates in the capillary endothelium. Electron microscopy revealed the presence of cytoplasmic tubular aggregates in the capillary endothelium of a sparsely granulated growth hormone cell adenoma removed surgically from a 25-year-old female patient with acromegaly. To our knowledge, this is the second publication describing these structures in hypophysial growth hormone cell adenomas."}
{"id": "PMID:190851", "title": "Chorionepitheliosis: A rare benign tropholblastic disease.", "content": "Chorionepitheliosis, a benign trophoblastic disease, is a rare entity since only 26 cases have been published. The diagnosis was made in two instances and microscopic, biological and clinical data are presented. The lesion must be distinguished from syncytial endometritis, chorioadenoma destruens and choriocarcinoma. The possible histogenesis is discussed.", "contents": "Chorionepitheliosis: A rare benign tropholblastic disease. Chorionepitheliosis, a benign trophoblastic disease, is a rare entity since only 26 cases have been published. The diagnosis was made in two instances and microscopic, biological and clinical data are presented. The lesion must be distinguished from syncytial endometritis, chorioadenoma destruens and choriocarcinoma. The possible histogenesis is discussed."}
{"id": "PMID:190853", "title": "Herpes encephalitis.", "content": "Four cases of herpes encephalitis treated with dexamethasone and cytarabine. Cases were all verified by brain biopsy and immunofluorescent techniques. Attention is called to the need for early diagnosis, but the difficulty of deciding when to perform brain biopsy is discussed. Early treatment with effective drugs is necessary to prevent permanent brain damage.", "contents": "Herpes encephalitis. Four cases of herpes encephalitis treated with dexamethasone and cytarabine. Cases were all verified by brain biopsy and immunofluorescent techniques. Attention is called to the need for early diagnosis, but the difficulty of deciding when to perform brain biopsy is discussed. Early treatment with effective drugs is necessary to prevent permanent brain damage."}
{"id": "PMID:190854", "title": "Chemical modification and characterization of enterotoxin from clostridium perfringens type A.", "content": "Enterotoxin from Clostridium perfringens type A has been purified. The enterotoxin was shown to be heat-labile, but re-activation of heat treated enterotoxin did occur down to an activity of 15 per cent of the native enterotoxin. The molecular weight was shown to be 34,000 by ultracentrifugation, and the molecular weight did not change significantly after treatment with 0.1 M beta-mercaptoethanol and 6 M guanidine hydrochloride. It was concluded that the enterotoxin consists of one single polypeptide chain. The enterotoxin did not lose any activity after treatment with iodoacetic acid and iodoacetamide, but a complete loss of activity was observed after succinylation.", "contents": "Chemical modification and characterization of enterotoxin from clostridium perfringens type A. Enterotoxin from Clostridium perfringens type A has been purified. The enterotoxin was shown to be heat-labile, but re-activation of heat treated enterotoxin did occur down to an activity of 15 per cent of the native enterotoxin. The molecular weight was shown to be 34,000 by ultracentrifugation, and the molecular weight did not change significantly after treatment with 0.1 M beta-mercaptoethanol and 6 M guanidine hydrochloride. It was concluded that the enterotoxin consists of one single polypeptide chain. The enterotoxin did not lose any activity after treatment with iodoacetic acid and iodoacetamide, but a complete loss of activity was observed after succinylation."}
{"id": "PMID:190855", "title": "In vitro stimulation of human lymphocytes by Bordetella Pertussis.", "content": "Bordetella pertussis (B.p.) induces blast transformation of human lymphocytes; whole killed B.p. are more efficient than extracts obtained by sonication. Similar responses were obtained with each of the four strains used in the Danish pertussis vaccine. B.p. with low amounts of Protective Antigen and Histamine-Sensitizing Factor also induced lymphocyte transformation, but were less toxic to the lymphocytes at high concentrations. The supernatants of B.p. cultures were purified with respect to Lymphocytosis Promoting Factor; evidence is presented that these purified fractions possess T-lymphocyte mitogenic activity. Lymphocytes from all normal humans were stimulated by B.p., including cells from cord blood. Cells from childbearing women, obtained immediately after delivery, showed a general depression of lymphocyte transformation including the response to B.p. Children with whooping cough had a lower lymphocyte response to B.p. than healthy children. A highly significant correlation was observed between the responses to B.p. and to E. coli in the adults and newborn examined. It is concluded that the major part of the lymphocyte transformation induced by B.p. is non-specific.", "contents": "In vitro stimulation of human lymphocytes by Bordetella Pertussis. Bordetella pertussis (B.p.) induces blast transformation of human lymphocytes; whole killed B.p. are more efficient than extracts obtained by sonication. Similar responses were obtained with each of the four strains used in the Danish pertussis vaccine. B.p. with low amounts of Protective Antigen and Histamine-Sensitizing Factor also induced lymphocyte transformation, but were less toxic to the lymphocytes at high concentrations. The supernatants of B.p. cultures were purified with respect to Lymphocytosis Promoting Factor; evidence is presented that these purified fractions possess T-lymphocyte mitogenic activity. Lymphocytes from all normal humans were stimulated by B.p., including cells from cord blood. Cells from childbearing women, obtained immediately after delivery, showed a general depression of lymphocyte transformation including the response to B.p. Children with whooping cough had a lower lymphocyte response to B.p. than healthy children. A highly significant correlation was observed between the responses to B.p. and to E. coli in the adults and newborn examined. It is concluded that the major part of the lymphocyte transformation induced by B.p. is non-specific."}
{"id": "PMID:190856", "title": "In vitro modulation of human leucocyte migration and migration inhibitory factor (LIF) activity by cyclic 3',5'-AMP and cyclic 3',5'-GMP.", "content": "The effects of cyclic 3', 5'-AMP (cAMP) and cyclic 3', 5'-GMP (cGMP) on the in vitro migration of human peripheral blood leucocytes under agarose and on the activity of leucocyte migration inhibitory factor (LIF) was studied. Leucocyte migration was not influenced by dibutyryl cAMP, while the dibutyryl derivative of cGMP significantly stimulated cell migration (1 x 10(-5)M). LIF-treated leucocytes partially escaped migration inhibition in the presence of dibutyryl cAMP (greater than or equal to 1 x 10(-6)M), while dibutyryl cGMP was inefficient. If the parent compounds cAMP and cGMP were tested, almost similar results would be obtained, although at higher concentrations of the drugs. These results represent initial experiments with a view to investigating the possible role of cyclic nucleotides in the expression of LIF activity.", "contents": "In vitro modulation of human leucocyte migration and migration inhibitory factor (LIF) activity by cyclic 3',5'-AMP and cyclic 3',5'-GMP. The effects of cyclic 3', 5'-AMP (cAMP) and cyclic 3', 5'-GMP (cGMP) on the in vitro migration of human peripheral blood leucocytes under agarose and on the activity of leucocyte migration inhibitory factor (LIF) was studied. Leucocyte migration was not influenced by dibutyryl cAMP, while the dibutyryl derivative of cGMP significantly stimulated cell migration (1 x 10(-5)M). LIF-treated leucocytes partially escaped migration inhibition in the presence of dibutyryl cAMP (greater than or equal to 1 x 10(-6)M), while dibutyryl cGMP was inefficient. If the parent compounds cAMP and cGMP were tested, almost similar results would be obtained, although at higher concentrations of the drugs. These results represent initial experiments with a view to investigating the possible role of cyclic nucleotides in the expression of LIF activity."}
{"id": "PMID:190852", "title": "Sympathetic influence on the nasal mucosa.", "content": "The tone of the resistance vessels determines the capillary flow and the tone of the capacitance vessels --the nasal patency. Lower impulse frequencies in the sympathetic nerves affect mainly the capacitance vessels, while higher frequencies affect both types of vessel. The existence of both alpha- and beta-adrenoreceptors and their distribution offer pharmacological ways to affect mainly one type of the vessels.", "contents": "Sympathetic influence on the nasal mucosa. The tone of the resistance vessels determines the capillary flow and the tone of the capacitance vessels --the nasal patency. Lower impulse frequencies in the sympathetic nerves affect mainly the capacitance vessels, while higher frequencies affect both types of vessel. The existence of both alpha- and beta-adrenoreceptors and their distribution offer pharmacological ways to affect mainly one type of the vessels."}
{"id": "PMID:190857", "title": "The pharmacology of a new hypoglycaemic agent N-[4-(2-(2,3-dihydrobenzo (b) furan-7-carboxamido)-ethyl)-benzenesulphonyl]-N'-cyclohexylurea (NOVO CS 476). II. Pharmacological studies on the mechanism of action.", "content": "The new sulphonylurea CS 476 does not potentiate the effect of insulin on plasma glucose levels in diabetic dogs in which an oral glucose load does not cause insulin release. In normal dogs propranolol 0.3 mg/kg intravenously inhibites the insulin release and the hypoglycaemia due to CS 476 suggesting involvement of beta-adrenergic receptors in its action on the pancreas. Pretreatment of dogs with phentolamine leads to an augmentation of the insulin response to CS 476.", "contents": "The pharmacology of a new hypoglycaemic agent N-[4-(2-(2,3-dihydrobenzo (b) furan-7-carboxamido)-ethyl)-benzenesulphonyl]-N'-cyclohexylurea (NOVO CS 476). II. Pharmacological studies on the mechanism of action. The new sulphonylurea CS 476 does not potentiate the effect of insulin on plasma glucose levels in diabetic dogs in which an oral glucose load does not cause insulin release. In normal dogs propranolol 0.3 mg/kg intravenously inhibites the insulin release and the hypoglycaemia due to CS 476 suggesting involvement of beta-adrenergic receptors in its action on the pancreas. Pretreatment of dogs with phentolamine leads to an augmentation of the insulin response to CS 476."}
{"id": "PMID:190858", "title": "A simple and inexpensive protein binding assay for cyclic AMP in biological materials.", "content": "We have developed a simple and inexpensive method for largecapacity cAMP determination in biological materials. The assay is based on competitive binding of 3H-cAMP to proteins isolated from rabbit skeletal muscle. Bovine serum albumin is added to the incubate to reduce non-specific interference. Separation of free and bound radioactivity is performed by (NH4)2SO4 precipitation allowing determination of either free or bound fraction. In the latter case, all procedures are performed in the same tube, to which is finally added 1.2 ml of scintillation fluid for counting. By this only one fourth. The method has been applied to rat tissue extracts and urine with satisfactory sensitivity, precision and accuracy.", "contents": "A simple and inexpensive protein binding assay for cyclic AMP in biological materials. We have developed a simple and inexpensive method for largecapacity cAMP determination in biological materials. The assay is based on competitive binding of 3H-cAMP to proteins isolated from rabbit skeletal muscle. Bovine serum albumin is added to the incubate to reduce non-specific interference. Separation of free and bound radioactivity is performed by (NH4)2SO4 precipitation allowing determination of either free or bound fraction. In the latter case, all procedures are performed in the same tube, to which is finally added 1.2 ml of scintillation fluid for counting. By this only one fourth. The method has been applied to rat tissue extracts and urine with satisfactory sensitivity, precision and accuracy."}
{"id": "PMID:190859", "title": "Plasma levels and electrophysiological effects of acebutolol (M & B 17.803) in the dog heart in situ.", "content": "The effect of acebutolol a beta-adrenergic receptor blocking agent was tested on the dog heart in situ. The drug decreased heart rate, and caused a reduction in the conduction velocity and a significant increase in the functional refractory period of the atrioventricular node. The functional and the effective refractory period of the right atrium was increased by acebutolol. During sinus rhythm, the drug did not affect conduction velocity in the rest of the conduction pathway. During atrial pacing, however, the intra-atrial and His-Purkinje conduction times were slightly increased. The plasma concentrations of acebutolol were in the range between 0.09 and 0.5 mug/ml, which is far below those values expected to cause a membrane-stabilizing or quinidine-like effect. The clinical applications of the results are discussed.", "contents": "Plasma levels and electrophysiological effects of acebutolol (M & B 17.803) in the dog heart in situ. The effect of acebutolol a beta-adrenergic receptor blocking agent was tested on the dog heart in situ. The drug decreased heart rate, and caused a reduction in the conduction velocity and a significant increase in the functional refractory period of the atrioventricular node. The functional and the effective refractory period of the right atrium was increased by acebutolol. During sinus rhythm, the drug did not affect conduction velocity in the rest of the conduction pathway. During atrial pacing, however, the intra-atrial and His-Purkinje conduction times were slightly increased. The plasma concentrations of acebutolol were in the range between 0.09 and 0.5 mug/ml, which is far below those values expected to cause a membrane-stabilizing or quinidine-like effect. The clinical applications of the results are discussed."}
{"id": "PMID:190860", "title": "Effects of cholinergic drugs and imidazole on Ca release and cyclic AMP formation in microsomal fractions from rabbit colon.", "content": "Following the addition of carbachol or acetylcholine to microsomal fractions isolated from rabbit colon which were preloaded with Ca, the ions were rapidly released. In the 35-45% fraction Ca was completely released within 10 min., but in the 35% fraction only 30% was released. Carbachol reduced the adenylate cyclase activity of the 35-45% fraction. Both these effects were blocked by atropine. Exogenous cyclic AMP completely inhibited the Ca-releasing action of carbachol in the 35% fraction and markedly reduced it in the 35-45% fraction. Imidazole released Ca from the 35-45% fraction and stimulated its phosphodiesterase activity. It is suggested that the microsomal fractions are parts of a Ca-sequestering system in smooth muscle which are able to bind Ca and which on the addition of some contracting drugs release the ions and thereby activate the contractile system. The release of Ca may partly at least be due to a reduction of the adenylate cyclase activity, although other mechanisms must also be considered.", "contents": "Effects of cholinergic drugs and imidazole on Ca release and cyclic AMP formation in microsomal fractions from rabbit colon. Following the addition of carbachol or acetylcholine to microsomal fractions isolated from rabbit colon which were preloaded with Ca, the ions were rapidly released. In the 35-45% fraction Ca was completely released within 10 min., but in the 35% fraction only 30% was released. Carbachol reduced the adenylate cyclase activity of the 35-45% fraction. Both these effects were blocked by atropine. Exogenous cyclic AMP completely inhibited the Ca-releasing action of carbachol in the 35% fraction and markedly reduced it in the 35-45% fraction. Imidazole released Ca from the 35-45% fraction and stimulated its phosphodiesterase activity. It is suggested that the microsomal fractions are parts of a Ca-sequestering system in smooth muscle which are able to bind Ca and which on the addition of some contracting drugs release the ions and thereby activate the contractile system. The release of Ca may partly at least be due to a reduction of the adenylate cyclase activity, although other mechanisms must also be considered."}
{"id": "PMID:190861", "title": "Antidiuretic and urinary cyclic AMP response of vasopressin in normal rats and in rats with lithium-polyuria.", "content": "The antidiuretic and urinary cyclic AMP response to supramaximal vasopressin infusion was studied in normal rats and in rats with lithium-polyuria. The animals were anaesthetized and then infused with a solution designed to produce excessive water diuresis and to lower basal cyclic AMP excretion. In 6 control animals not infused with vasopressin (1) urinary cyclic AMP excretion decreased during the infusion period. Vasopressin infusion (300 muU/min.) consistantly induced antidiuresis in all of 13 control rats (II); but the urinary cyclic AMP response varied individually from a significant increase in 6 animals to either no change or to a decrease in the remaining animals. The antidiuretic response to vasopressin was inhibited by 85% in 10 animals with marked polyuria induced by lithium administration (III). None of the animals in this group showed a significant increase of cyclic AMP excretion in response to vasopressin. The average rate of cyclic AMP excretion, which was equal in the two groups before vasopressin, was signifimantly lower in group III than in group II during vasopressin infusion. It is suggested that the increase in cyclic AMP excretion during vasopressin antidiuresis, although not consistant, most likely reflects hormone-induced changes of intracellular cyclic AMP levels in the renal medulla. Thus, the data suggest that the nephrogenic diabetes insipidus syndrome produced by lithium is associated with a defect in the renal formation of cyclic AMP in response to vasopressin.", "contents": "Antidiuretic and urinary cyclic AMP response of vasopressin in normal rats and in rats with lithium-polyuria. The antidiuretic and urinary cyclic AMP response to supramaximal vasopressin infusion was studied in normal rats and in rats with lithium-polyuria. The animals were anaesthetized and then infused with a solution designed to produce excessive water diuresis and to lower basal cyclic AMP excretion. In 6 control animals not infused with vasopressin (1) urinary cyclic AMP excretion decreased during the infusion period. Vasopressin infusion (300 muU/min.) consistantly induced antidiuresis in all of 13 control rats (II); but the urinary cyclic AMP response varied individually from a significant increase in 6 animals to either no change or to a decrease in the remaining animals. The antidiuretic response to vasopressin was inhibited by 85% in 10 animals with marked polyuria induced by lithium administration (III). None of the animals in this group showed a significant increase of cyclic AMP excretion in response to vasopressin. The average rate of cyclic AMP excretion, which was equal in the two groups before vasopressin, was signifimantly lower in group III than in group II during vasopressin infusion. It is suggested that the increase in cyclic AMP excretion during vasopressin antidiuresis, although not consistant, most likely reflects hormone-induced changes of intracellular cyclic AMP levels in the renal medulla. Thus, the data suggest that the nephrogenic diabetes insipidus syndrome produced by lithium is associated with a defect in the renal formation of cyclic AMP in response to vasopressin."}
{"id": "PMID:190863", "title": "The interaction of cyproheptadine with agents affecting neuromuscular transmission.", "content": "Using the rat phrenic nerve diaphragm, cyproheptadine at concentrations of 1 to 8 mug/ml did not affect or slightly augmented indirect muscle twitches, but potentiated blockade by tubocurarine, decamethonium and succinylcholine, and antagonized the augmentation of twitches by neostigmine. Ketamine, choline and tetraethylammonium at concentrations causing no blockade produced, when given after cyproheptadine (6 mug/ml), a high degree of blockade. At concentrations of 9 to 20 mug/ml, cyproheptadine induced neuromuscular blockade which was slow in onset, more apparent at higher rate of stimulation and was not reversed by neostigmine, choline or tetraethylammonium. In the cat tibialis anterior muscle, it potentiated blockade by tubocurarine, decamethonium and succinylcholine, and blocked acetylcholine twitches. In the chick biventer cervicis muscle, the durg was more effective in blocking indirect twitches than responses to carbachol.", "contents": "The interaction of cyproheptadine with agents affecting neuromuscular transmission. Using the rat phrenic nerve diaphragm, cyproheptadine at concentrations of 1 to 8 mug/ml did not affect or slightly augmented indirect muscle twitches, but potentiated blockade by tubocurarine, decamethonium and succinylcholine, and antagonized the augmentation of twitches by neostigmine. Ketamine, choline and tetraethylammonium at concentrations causing no blockade produced, when given after cyproheptadine (6 mug/ml), a high degree of blockade. At concentrations of 9 to 20 mug/ml, cyproheptadine induced neuromuscular blockade which was slow in onset, more apparent at higher rate of stimulation and was not reversed by neostigmine, choline or tetraethylammonium. In the cat tibialis anterior muscle, it potentiated blockade by tubocurarine, decamethonium and succinylcholine, and blocked acetylcholine twitches. In the chick biventer cervicis muscle, the durg was more effective in blocking indirect twitches than responses to carbachol."}
{"id": "PMID:190865", "title": "Potentiation by carbachol and aminophylline of histamine- and db-cAMP-induced parietal cell activity in isolated gastric glands.", "content": "The response to combinations of gastric acid secretagogues was studied in isolated glands from the rabbit gastric mucosa in terms of changes in oxygen consumption and accumulation of the weak base aminopyrine (AP). The latter reflects the acid secreting status of the glands. The following secretagogues were investigated: histamine, carbachol, aminophylline and db-cAMP. The histamine respiratory dose-response curve was shifted to the left in the presence of the phosphodiesterase inhibitor aminophylline. Both ED-50 and maximum response were significantly increased. Histamine-induced AP accumulation was also strongly enhanced by aminophylline (5 X 10(-4) M). These results are consistent with the hypothesis that histamine stimulation of acid secretion is mediated by cyclic AMP. Carbachol-stimulated oxygen consumption could not be potentiated by aminophylline and the combined effect was only additive. The response to a combination of histamine and carbachol was a significant increase in oxygen consumption above what could be expected from an additive effect alone. Carbachol addition to glands prestimulated with histamine gave a rapid increase in the respiratory rate resulting in a new steady state level within 10-15 min, as compared with a time constant of about 40 min when both drugs were added simultaneously. Likewise AP accumulation increased more rapidly and reached a higher value after addition of histamine + carbachol as compared with histamine alone. The db-cAMP-stimulated oxygen consumption was in all respects equally affected by carbachol as was histamine stimulation. This indicates that the well known cholinergic potentiation of histamine stimulation is not due to an increased sensitivity of the histamine receptor but is of a more general nature. A mechanism involving intracellular availability of Ca2+ is proposed as one possible explanation of this potentiation.", "contents": "Potentiation by carbachol and aminophylline of histamine- and db-cAMP-induced parietal cell activity in isolated gastric glands. The response to combinations of gastric acid secretagogues was studied in isolated glands from the rabbit gastric mucosa in terms of changes in oxygen consumption and accumulation of the weak base aminopyrine (AP). The latter reflects the acid secreting status of the glands. The following secretagogues were investigated: histamine, carbachol, aminophylline and db-cAMP. The histamine respiratory dose-response curve was shifted to the left in the presence of the phosphodiesterase inhibitor aminophylline. Both ED-50 and maximum response were significantly increased. Histamine-induced AP accumulation was also strongly enhanced by aminophylline (5 X 10(-4) M). These results are consistent with the hypothesis that histamine stimulation of acid secretion is mediated by cyclic AMP. Carbachol-stimulated oxygen consumption could not be potentiated by aminophylline and the combined effect was only additive. The response to a combination of histamine and carbachol was a significant increase in oxygen consumption above what could be expected from an additive effect alone. Carbachol addition to glands prestimulated with histamine gave a rapid increase in the respiratory rate resulting in a new steady state level within 10-15 min, as compared with a time constant of about 40 min when both drugs were added simultaneously. Likewise AP accumulation increased more rapidly and reached a higher value after addition of histamine + carbachol as compared with histamine alone. The db-cAMP-stimulated oxygen consumption was in all respects equally affected by carbachol as was histamine stimulation. This indicates that the well known cholinergic potentiation of histamine stimulation is not due to an increased sensitivity of the histamine receptor but is of a more general nature. A mechanism involving intracellular availability of Ca2+ is proposed as one possible explanation of this potentiation."}
{"id": "PMID:190866", "title": "Pineal serotonin metabolism in non-innervated perinatal glands before and after intraocular maturation: supersensitivity of adrenoceptors that have never been innervated.", "content": "Transplantations were made of fetal pineal glands (crown-rump length, CRL, 19-30 mm) or pineal glands from adult male rats to the anterior chamber of the eye of the rat. Studies were performed with regard to the importance of the age of the donor animal (and thereby the degree of maturation and innervation of the gland to be transplanted) for the possible development of denervation supersensitivity. The transplants were cultured in a medium containing 14C-serotonin. Increased production of 14C-N-acetylserotonin (NAcS) was used as the main criterion for beta-adrenergic stimulation. 4 experimental groups were obtained by transplanting fetal or adult pineals to intact or sympathetically denervated eyes. In all 4 groups beta1-stimulation (KWD 2033 10(-6) M) increased 14C-NAcS formation. The response to beta-stimulation was significantly higher in denervated fetal pineal transplants than in innervated fetal transplants and thus demonstrating beta-receptor supersensitivity. It was concluded that a) the ability to respond to beta-adrenoreceptor stimulation with increased 14C-NAcS formation develops between the 18th and 20th day of gestation, b) transplants derived from fetal as well as from adult rats can respond to beta-adrenergic stimulation, c) this sensitivity also develops in oculo in transplants that at the time of transplantation lacked the capacity to increase their 14C-NAcS formation in response to treatment with beta-agonist, d) denervation supersensitivity occurs in fetal transplants that became mature in sympathetically denervated eyes.", "contents": "Pineal serotonin metabolism in non-innervated perinatal glands before and after intraocular maturation: supersensitivity of adrenoceptors that have never been innervated. Transplantations were made of fetal pineal glands (crown-rump length, CRL, 19-30 mm) or pineal glands from adult male rats to the anterior chamber of the eye of the rat. Studies were performed with regard to the importance of the age of the donor animal (and thereby the degree of maturation and innervation of the gland to be transplanted) for the possible development of denervation supersensitivity. The transplants were cultured in a medium containing 14C-serotonin. Increased production of 14C-N-acetylserotonin (NAcS) was used as the main criterion for beta-adrenergic stimulation. 4 experimental groups were obtained by transplanting fetal or adult pineals to intact or sympathetically denervated eyes. In all 4 groups beta1-stimulation (KWD 2033 10(-6) M) increased 14C-NAcS formation. The response to beta-stimulation was significantly higher in denervated fetal pineal transplants than in innervated fetal transplants and thus demonstrating beta-receptor supersensitivity. It was concluded that a) the ability to respond to beta-adrenoreceptor stimulation with increased 14C-NAcS formation develops between the 18th and 20th day of gestation, b) transplants derived from fetal as well as from adult rats can respond to beta-adrenergic stimulation, c) this sensitivity also develops in oculo in transplants that at the time of transplantation lacked the capacity to increase their 14C-NAcS formation in response to treatment with beta-agonist, d) denervation supersensitivity occurs in fetal transplants that became mature in sympathetically denervated eyes."}
{"id": "PMID:190867", "title": "Time course of changes in human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity.", "content": "Succinate dehydrogenase (SDH) and cytochrome oxidase activities in the lateral vastus of the human quadriceps femoris muscle together with total body VO2 max were followed during an 8-10 week period of endurance training (n = 13) and a successive 6 week period without training (n = 8). During the training period there was a gradual increase in both VO2 max and muscle oxidative enzyme activities, all being significantly different from the pre-training levels after 3 weeks of training. After 8 weeks of training VO2 max was 19%, vastus lateralis SDH 32%, and cytochrome oxidase activity 35% above the pre-training levels respectively. 6 weeks post training VO2 max was still 16% above the pre-training level, and not significantly different from the level at the end of training (p greater than 0.2). In contrast vastus lateralis SDH activity had returned to the pre-training level. Cytochrome oxidase activity had returned to the pre-training level within two weeks post-training. The significantly faster post-training decline in skeletal muscle oxidative enzyme activities in contrast to that of the VO2 max indicates that an enhancement of the oxidative potential in skeletal muscle is not a necessity for a high VO2 max. Moreover, the fast return to the pre-training level of both SDH and cytochrome oxidase activities indicate a high turnover rate of enzymes in the TCA cycle as well as the respiratory chain.", "contents": "Time course of changes in human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity. Succinate dehydrogenase (SDH) and cytochrome oxidase activities in the lateral vastus of the human quadriceps femoris muscle together with total body VO2 max were followed during an 8-10 week period of endurance training (n = 13) and a successive 6 week period without training (n = 8). During the training period there was a gradual increase in both VO2 max and muscle oxidative enzyme activities, all being significantly different from the pre-training levels after 3 weeks of training. After 8 weeks of training VO2 max was 19%, vastus lateralis SDH 32%, and cytochrome oxidase activity 35% above the pre-training levels respectively. 6 weeks post training VO2 max was still 16% above the pre-training level, and not significantly different from the level at the end of training (p greater than 0.2). In contrast vastus lateralis SDH activity had returned to the pre-training level. Cytochrome oxidase activity had returned to the pre-training level within two weeks post-training. The significantly faster post-training decline in skeletal muscle oxidative enzyme activities in contrast to that of the VO2 max indicates that an enhancement of the oxidative potential in skeletal muscle is not a necessity for a high VO2 max. Moreover, the fast return to the pre-training level of both SDH and cytochrome oxidase activities indicate a high turnover rate of enzymes in the TCA cycle as well as the respiratory chain."}
{"id": "PMID:190868", "title": "Conjugated catechol derivatives in a transplantable islet cell tumour of the golden hamster.", "content": "Two glucuronidated catechol have been identified in a transplantable islet cell tumour of the golden hamster, i.e. dopamine-4-O-glucuronide and 3-methoxytyramine-4-O-glucuronide. L-dopa is rapidly metabolized in the tumour to one or both of these glucuronides. Incubation of tumour homogenates in the presence of beta-glucuronidase shows that dopamine-4-O-glucuronide is present in the tumour in extremely high concentrations.", "contents": "Conjugated catechol derivatives in a transplantable islet cell tumour of the golden hamster. Two glucuronidated catechol have been identified in a transplantable islet cell tumour of the golden hamster, i.e. dopamine-4-O-glucuronide and 3-methoxytyramine-4-O-glucuronide. L-dopa is rapidly metabolized in the tumour to one or both of these glucuronides. Incubation of tumour homogenates in the presence of beta-glucuronidase shows that dopamine-4-O-glucuronide is present in the tumour in extremely high concentrations."}
{"id": "PMID:190869", "title": "Actomyosin ATPase, myokinase, CPK and LDH in human fast and slow twitch muscle fibres.", "content": "The enzyme activities of Mg2+ stimulated ATPase, creatine phosphokinase (CPK), myokinase (MK) and lactate dehydrogenase (LDH) were determined in pooled fast twitch (FT) and slow twitch (ST) human skeletal muscle fibers, dissected out from freeze-dried muscle biopsy material. All enzymes investigated demonstrated higher activities in FT fibres. The ratio in enzyme activity between fibre types was greatest for Mg2+ stimulated ATPase (3:1) and smallest for CPK (1.3:1). In addition, the isozyme patterns of CPK, MK and LDH were studied by means of isoelectric focusing (CPK and MK) and discelectrophoresis (LDH). A difference was observed between fibre types with respect to the isozyme distribution of MK and LDH, whereas the CPK isozyme pattern was similar in both fibre types. These results on separated human FT and ST fibres were essentially in conformity with what has earlier been indicated from experiments on mixed muscle homogenates.", "contents": "Actomyosin ATPase, myokinase, CPK and LDH in human fast and slow twitch muscle fibres. The enzyme activities of Mg2+ stimulated ATPase, creatine phosphokinase (CPK), myokinase (MK) and lactate dehydrogenase (LDH) were determined in pooled fast twitch (FT) and slow twitch (ST) human skeletal muscle fibers, dissected out from freeze-dried muscle biopsy material. All enzymes investigated demonstrated higher activities in FT fibres. The ratio in enzyme activity between fibre types was greatest for Mg2+ stimulated ATPase (3:1) and smallest for CPK (1.3:1). In addition, the isozyme patterns of CPK, MK and LDH were studied by means of isoelectric focusing (CPK and MK) and discelectrophoresis (LDH). A difference was observed between fibre types with respect to the isozyme distribution of MK and LDH, whereas the CPK isozyme pattern was similar in both fibre types. These results on separated human FT and ST fibres were essentially in conformity with what has earlier been indicated from experiments on mixed muscle homogenates."}
{"id": "PMID:190878", "title": "Electron microscopic studies of the parathyroid gland of senile dogs.", "content": "The parathyroid gland of healthy senile dogs aged 8.5 to 15 years was compared with that of mature control dogs by examination with the electron microscope. Preparations fixed by perfusion with glutaraldehyde showed the cytoplasmic matrix of most parenchymal cells to be uniformly dense. None of the cells were of the extremely light type and dark cells were much less frequently noted than in preparations fixed by immersion in glutaraldehyde or osmium tetroxide. Syncytial cells and so-called coloid follicles were more frequent in senile dogs than in control dogs. It was suggested that the content of the latter structures is not colloid but necrotic substance hiving origin from the parenchymal cells and that perhaps the occasional cells containing large, membrane-bound inclusions may be degenerating cells which ultimately produce this necrotic substance. Oxyphil cells and mitochondria-rich cells of another type were found in all senile dogs, but not in the controls. These cells, especially the mitochondria-rich cells, frequently contained bizarre mitochondria that were modified in shape, size and arrangement. The most striking feature of these mitochondria was the concentric arrangement of elongated mitochondria which seemed to consist of densely layered cup-shaped mitochondria. Such mitochondria were noted in all senile dogs aged ten years and over. The significance of mitochondrial ple-morphism in the parathyroid gland of senile dogs was discussed.", "contents": "Electron microscopic studies of the parathyroid gland of senile dogs. The parathyroid gland of healthy senile dogs aged 8.5 to 15 years was compared with that of mature control dogs by examination with the electron microscope. Preparations fixed by perfusion with glutaraldehyde showed the cytoplasmic matrix of most parenchymal cells to be uniformly dense. None of the cells were of the extremely light type and dark cells were much less frequently noted than in preparations fixed by immersion in glutaraldehyde or osmium tetroxide. Syncytial cells and so-called coloid follicles were more frequent in senile dogs than in control dogs. It was suggested that the content of the latter structures is not colloid but necrotic substance hiving origin from the parenchymal cells and that perhaps the occasional cells containing large, membrane-bound inclusions may be degenerating cells which ultimately produce this necrotic substance. Oxyphil cells and mitochondria-rich cells of another type were found in all senile dogs, but not in the controls. These cells, especially the mitochondria-rich cells, frequently contained bizarre mitochondria that were modified in shape, size and arrangement. The most striking feature of these mitochondria was the concentric arrangement of elongated mitochondria which seemed to consist of densely layered cup-shaped mitochondria. Such mitochondria were noted in all senile dogs aged ten years and over. The significance of mitochondrial ple-morphism in the parathyroid gland of senile dogs was discussed."}
{"id": "PMID:190879", "title": "Treatment of toxic megacolon. A comparative review of 29 patients.", "content": "A review of 29 patients with toxic megacolon complicating ulcerative colitis was undertaken to (1) compare the results of medical and surgical treatment; (2) determine the optimal timing for surgical intervention, and (3) identify possible precipitating factors. Twenty-one patients were treated medically with nasogastric suction, steroids, parental fluids, blood transfusions, and antimicrobial agents. Of the 21 patients, 11 (53%) showed improvement by subjective and objective criteria  and 10 (47%) failed to respond. Sixteen patients were treated surgically. This group was subdivided into 8 patients who failed to respond to medical treatment and 8 treated surgically. Total proctocolectomy with ileostomy was performed in 8 and subtotal colectomy and ileoproctostomy in 8, with subsequent proctectomy and ileostomy in 6 patient. Six of 8 patients (75%) treated primarily surgically improved, and 2 (25%) died. Seven of 8 patients (87.5%) treated surgically after failure of medical trial showed definite postoperative improvement, and 1 (12.5%) failed. Those who were operated on within the first 48-72 hr after the diagnosis of toxic megacolon was made responded uniformly well. Anticholinergics, opiates,, barium enema, and colonoscopy were identified as possible precipitating factors in 70% of cases. The results of this tudy in this patient population indicate that early surgical therapy in toxic megacolon is associated with better results than medical therapy (P less than 0.025). Although intensive, optimal medical therapy plays a significant role in the management of toxic megacolon, failure to induce rapid improvement within 48-72 hr constitutes an indication for definitive surgical treatment.", "contents": "Treatment of toxic megacolon. A comparative review of 29 patients. A review of 29 patients with toxic megacolon complicating ulcerative colitis was undertaken to (1) compare the results of medical and surgical treatment; (2) determine the optimal timing for surgical intervention, and (3) identify possible precipitating factors. Twenty-one patients were treated medically with nasogastric suction, steroids, parental fluids, blood transfusions, and antimicrobial agents. Of the 21 patients, 11 (53%) showed improvement by subjective and objective criteria  and 10 (47%) failed to respond. Sixteen patients were treated surgically. This group was subdivided into 8 patients who failed to respond to medical treatment and 8 treated surgically. Total proctocolectomy with ileostomy was performed in 8 and subtotal colectomy and ileoproctostomy in 8, with subsequent proctectomy and ileostomy in 6 patient. Six of 8 patients (75%) treated primarily surgically improved, and 2 (25%) died. Seven of 8 patients (87.5%) treated surgically after failure of medical trial showed definite postoperative improvement, and 1 (12.5%) failed. Those who were operated on within the first 48-72 hr after the diagnosis of toxic megacolon was made responded uniformly well. Anticholinergics, opiates,, barium enema, and colonoscopy were identified as possible precipitating factors in 70% of cases. The results of this tudy in this patient population indicate that early surgical therapy in toxic megacolon is associated with better results than medical therapy (P less than 0.025). Although intensive, optimal medical therapy plays a significant role in the management of toxic megacolon, failure to induce rapid improvement within 48-72 hr constitutes an indication for definitive surgical treatment."}
{"id": "PMID:190880", "title": "The biochemistry of the renin-angiotensin system and its role in hypertension.", "content": "The renin-angiotensin system has an important role in maintaining elevated blood pressure levels in certain forms of experimental and human hypertension. Renin, an enzyme produced by the juxtaglomerular cells of the kidney, acts on a protein substrate found in the alpha 2-globulin fraction of the plasma to produce a decapeptide, angiotensin I. This decapeptide is not directly pressor, but on passage through the pulmonary circulation is converted to an octapeptide, angiotensin II, a very potent pressor substance which acts by causing constriction of arteriolar smooth muscle. In addition to its direct action which increases blood pressure, angiotensin II acts on the adrenal cortex to cause the release of the sodium-retaining hormone aldosterone. Recent evidence suggests that this action may be mediated by the heptapeptide, angiotensin III. Both renin and its protein substrate exist in multiple forms and renin may also exist as a high molecular-weight \"pro-hormone,\" although the physiologic significance of these forms is not clear. The elucidation of the biochemistry of the renin-angiotensin system has provided us with inhibitors which allow the system to be blocked effectively in vivo. Thus, angiotensin antagonists such as Sar 1, IIe 8-angiotensin II and converting enzyme inhibitors such as BPP 9a (SQ 20881) have proved useful in the study of experimental and human hypertension.", "contents": "The biochemistry of the renin-angiotensin system and its role in hypertension. The renin-angiotensin system has an important role in maintaining elevated blood pressure levels in certain forms of experimental and human hypertension. Renin, an enzyme produced by the juxtaglomerular cells of the kidney, acts on a protein substrate found in the alpha 2-globulin fraction of the plasma to produce a decapeptide, angiotensin I. This decapeptide is not directly pressor, but on passage through the pulmonary circulation is converted to an octapeptide, angiotensin II, a very potent pressor substance which acts by causing constriction of arteriolar smooth muscle. In addition to its direct action which increases blood pressure, angiotensin II acts on the adrenal cortex to cause the release of the sodium-retaining hormone aldosterone. Recent evidence suggests that this action may be mediated by the heptapeptide, angiotensin III. Both renin and its protein substrate exist in multiple forms and renin may also exist as a high molecular-weight \"pro-hormone,\" although the physiologic significance of these forms is not clear. The elucidation of the biochemistry of the renin-angiotensin system has provided us with inhibitors which allow the system to be blocked effectively in vivo. Thus, angiotensin antagonists such as Sar 1, IIe 8-angiotensin II and converting enzyme inhibitors such as BPP 9a (SQ 20881) have proved useful in the study of experimental and human hypertension."}
{"id": "PMID:190881", "title": "Conversion of angiotensin I to angiotensin II.", "content": "The angiotensin I converting enzyme has two important functions: it inactivates bradykinin and converts angiotensin I to angiotensin II. Inhibition of the enzyme blocks the renin-angiotensin system and decreases systemic blood pressure if the pressure is maintained or increased by renin. The enzyme occurs in a variety of tissues and cell forms. The vascular endothelial cells of the lung and of peripheral blood vessels, and the epithelial cells of the kidney tubules are major sources of the enzyme. In addition to inactivating hypotensive peptides and activating a hypertensive one in the systemic circulation, the enzyme may affect organ functions by hydrolyzing peptides that are formed and released locally.", "contents": "Conversion of angiotensin I to angiotensin II. The angiotensin I converting enzyme has two important functions: it inactivates bradykinin and converts angiotensin I to angiotensin II. Inhibition of the enzyme blocks the renin-angiotensin system and decreases systemic blood pressure if the pressure is maintained or increased by renin. The enzyme occurs in a variety of tissues and cell forms. The vascular endothelial cells of the lung and of peripheral blood vessels, and the epithelial cells of the kidney tubules are major sources of the enzyme. In addition to inactivating hypotensive peptides and activating a hypertensive one in the systemic circulation, the enzyme may affect organ functions by hydrolyzing peptides that are formed and released locally."}
{"id": "PMID:190882", "title": "Unexpected pressor responses to propranolol in essential hypertension. An interaction between renin, aldosterone and sympathetic activity.", "content": "The blood pressure response to propranolol treatment was analyzed retrospectively in 187 patients with benign essential hypertension. In most patients (102 patients, 54 per cent) systolic and/or diastolic blood pressure was decreased by more than 10 per cent (responders). No significant change in blood pressure occurred in 35 per cent (65 patients) of the patients (nonresponders). Surprisingly, in 20 patients (11 per cent) systolic (8 patients) and/or diastolic (14 patients) blood pressure was increased by more than 7 per cent (pressor-responders). All three subgroups received similar amounts of propranolol and irrespective of the effect on the blood pressure, propranolol produced a similar reduction in pulse rates, suggesting similar degree of beta blockade. The three subgroups did not differ in their clinical characteristics, except that the nonresponders were significantly older than the responders. Pretreatment renin values were highest in the responders, somewhat lower in the nonresponders and significantly lower in the pressor-responders. In a representative subset of 66 patients, control and treatment values for plasma renin activity and aldosterone excretion were compared. The responders had the most pronounced decreases in both renin and aldosterone. In striking contrast, no significant changes were observed in the two hormones in those patients whose blood pressure levels rose. Moreover, in the pressor-responders, the drug produced the greatest increases in body weight, reflecting sodium retention. The differences in blood pressure responses observed in different patients may be explained by various interplays between the drug-induced suppression of renin and aldosterone, and the operation of unapposed or reactive alpha sympathetic activity. The latter is presumably active in all patients tending to cause vasoconstriction and hence an increase in peripheral resistance. In the pressor-responders such unopposed alpha-tone combined with the demonstrated lack of renin and aldosterone suppression with attendant fluid retention could work to produce the paradoxical pressor responses. In contrast, in those whose blood pressure levels drop, the drug-induced suppression of renin leads to decreased peripheral resistance despite the unopposed alphatone. The accompanying decrease in aldosterone limits sodium retention and contributes to the fall in blood pressure levels.", "contents": "Unexpected pressor responses to propranolol in essential hypertension. An interaction between renin, aldosterone and sympathetic activity. The blood pressure response to propranolol treatment was analyzed retrospectively in 187 patients with benign essential hypertension. In most patients (102 patients, 54 per cent) systolic and/or diastolic blood pressure was decreased by more than 10 per cent (responders). No significant change in blood pressure occurred in 35 per cent (65 patients) of the patients (nonresponders). Surprisingly, in 20 patients (11 per cent) systolic (8 patients) and/or diastolic (14 patients) blood pressure was increased by more than 7 per cent (pressor-responders). All three subgroups received similar amounts of propranolol and irrespective of the effect on the blood pressure, propranolol produced a similar reduction in pulse rates, suggesting similar degree of beta blockade. The three subgroups did not differ in their clinical characteristics, except that the nonresponders were significantly older than the responders. Pretreatment renin values were highest in the responders, somewhat lower in the nonresponders and significantly lower in the pressor-responders. In a representative subset of 66 patients, control and treatment values for plasma renin activity and aldosterone excretion were compared. The responders had the most pronounced decreases in both renin and aldosterone. In striking contrast, no significant changes were observed in the two hormones in those patients whose blood pressure levels rose. Moreover, in the pressor-responders, the drug produced the greatest increases in body weight, reflecting sodium retention. The differences in blood pressure responses observed in different patients may be explained by various interplays between the drug-induced suppression of renin and aldosterone, and the operation of unapposed or reactive alpha sympathetic activity. The latter is presumably active in all patients tending to cause vasoconstriction and hence an increase in peripheral resistance. In the pressor-responders such unopposed alpha-tone combined with the demonstrated lack of renin and aldosterone suppression with attendant fluid retention could work to produce the paradoxical pressor responses. In contrast, in those whose blood pressure levels drop, the drug-induced suppression of renin leads to decreased peripheral resistance despite the unopposed alphatone. The accompanying decrease in aldosterone limits sodium retention and contributes to the fall in blood pressure levels."}
{"id": "PMID:190883", "title": "Role of anaerobic bacteria in spontaneous peritonitis of cirrhosis: report of two cases and review of the literature.", "content": "The role of anaerobic or microaerophillic bacteria in spontaneous peritonitis of cirrhosis has not been clearly defined. Among 126 cases recorded in the literature, in only eight (6 per cent), including the two reported here, was bacterascites associated with anaerobic or microaerophilic bacteria. Clinical features in these cases were indistinguishable from those associated with aerobic bacteria. However, polymicrobial bacterascites occurred in four of eight cases associated with anaerobes, as contrasted with only 10 of 118 cases (8 per cent) associated with aerobes alone. On the other hand, concurrent bacteremia occurred in only one of eight cases associated with anaerobes as contrasted with 52 of 118 cases (44 per cent) of aerobic spontaneous peritonitis. Experimental evidence is cited in an attempt to explain this relatively low incidence of spontaneous peritonitis associated with anaerobic or microaerophilic bacteria, despite the high density of these organisms in the normal bowel flora.", "contents": "Role of anaerobic bacteria in spontaneous peritonitis of cirrhosis: report of two cases and review of the literature. The role of anaerobic or microaerophillic bacteria in spontaneous peritonitis of cirrhosis has not been clearly defined. Among 126 cases recorded in the literature, in only eight (6 per cent), including the two reported here, was bacterascites associated with anaerobic or microaerophilic bacteria. Clinical features in these cases were indistinguishable from those associated with aerobic bacteria. However, polymicrobial bacterascites occurred in four of eight cases associated with anaerobes, as contrasted with only 10 of 118 cases (8 per cent) associated with aerobes alone. On the other hand, concurrent bacteremia occurred in only one of eight cases associated with anaerobes as contrasted with 52 of 118 cases (44 per cent) of aerobic spontaneous peritonitis. Experimental evidence is cited in an attempt to explain this relatively low incidence of spontaneous peritonitis associated with anaerobic or microaerophilic bacteria, despite the high density of these organisms in the normal bowel flora."}
{"id": "PMID:190884", "title": "Cytomegalovirus mononucleosis in a healthy adult: association with hepatitis, secondary Epstein-Barr Virus antibody response and immunosuppression.", "content": "A 35 year old previously healthy physician had clinical manifestations of a mononucleosis illness complicated by arthralgia, vesicular pharyngitis and hepatitis. Initially, the patient had cytomegalovirus (CMV) viremia (predominantly in polymorphonuclear leukocytes) followed by the presence of CMV in the urine, throat and semen. He also had an antibody response to the Epstein-Barr virus which appeared to be a secondary type. During the acute phase of illness, only 7 per cent of the patient's lymphocytes formed spontaneous T cell rosettes as compared to a normal value of 65 to 70 per cent. Concurrently, evidence of abnormal delayed hypersensitivity was manifested by the loss of reactivity to mumps skin test antigen. All clinical and laboratory abnormalities except for the persistence of CMV in the pharynx, urine and semen returned to normal after resolution of the clinical illness.", "contents": "Cytomegalovirus mononucleosis in a healthy adult: association with hepatitis, secondary Epstein-Barr Virus antibody response and immunosuppression. A 35 year old previously healthy physician had clinical manifestations of a mononucleosis illness complicated by arthralgia, vesicular pharyngitis and hepatitis. Initially, the patient had cytomegalovirus (CMV) viremia (predominantly in polymorphonuclear leukocytes) followed by the presence of CMV in the urine, throat and semen. He also had an antibody response to the Epstein-Barr virus which appeared to be a secondary type. During the acute phase of illness, only 7 per cent of the patient's lymphocytes formed spontaneous T cell rosettes as compared to a normal value of 65 to 70 per cent. Concurrently, evidence of abnormal delayed hypersensitivity was manifested by the loss of reactivity to mumps skin test antigen. All clinical and laboratory abnormalities except for the persistence of CMV in the pharynx, urine and semen returned to normal after resolution of the clinical illness."}
{"id": "PMID:190887", "title": "Exogenous estrogen and endometrial carcinoma: case-control and incidence study.", "content": "Recent independent case-control studies have indicated that treatment with exogenous estrogen is associated with an increase in the risk of endometrial cancer. This question was studied in Olmsted County, Minnesota, by identifying all cases of endometrial cancer among residents over a 30 year period (1945 through 1974) and by matching four controls to each of the 145 patients. The rate of past exposure to any exogenous estrogen for any duration was about the same for patients as for controls. However, the estimated relative risk of endometrial cancer associated with conjugated estrogen treatment of 6 months or longer was 4.9 (P less than 0.01), and this increased to 7.9 (P less than 0.01) with exposure for 3 years or longer. The risk increased with larger doses (1.25 mg. or more) and continuous administration of conjugated estrogens. The incidence of endometrial carcinoma over the three decades of the study, corrected for an increasing rate of hysterectomy, was constant. Thus to this time, the low rate of use of conjugated estrogens in this region over the past 30 years apparently has not had an appreciable impact on the incidence of endometrial cancer.", "contents": "Exogenous estrogen and endometrial carcinoma: case-control and incidence study. Recent independent case-control studies have indicated that treatment with exogenous estrogen is associated with an increase in the risk of endometrial cancer. This question was studied in Olmsted County, Minnesota, by identifying all cases of endometrial cancer among residents over a 30 year period (1945 through 1974) and by matching four controls to each of the 145 patients. The rate of past exposure to any exogenous estrogen for any duration was about the same for patients as for controls. However, the estimated relative risk of endometrial cancer associated with conjugated estrogen treatment of 6 months or longer was 4.9 (P less than 0.01), and this increased to 7.9 (P less than 0.01) with exposure for 3 years or longer. The risk increased with larger doses (1.25 mg. or more) and continuous administration of conjugated estrogens. The incidence of endometrial carcinoma over the three decades of the study, corrected for an increasing rate of hysterectomy, was constant. Thus to this time, the low rate of use of conjugated estrogens in this region over the past 30 years apparently has not had an appreciable impact on the incidence of endometrial cancer."}
{"id": "PMID:190888", "title": "The value of urinary steroid analysis in chorionic neoplasia.", "content": "The profile of urinary neutral steroids was investigated in normal pregnancy and chorionic neoplasia by gas-liquid chromatography. The whole chramatogram was divided into three metabolically distinct fractions. The excretion of fraction 2, including four menstruation-dependent steroids (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, and pregnanetrial), was remarkably increased in normal pregnancy as compared with that in nonpregnant controls. But the same parameter was differentially reduced in hydatidiform mole (HM) and chorioadenoma destruens (CA) as compared with normal pregnancy, and the ratio of fraction 2 to fraction 1 (11-deoxy-17-ketosteroids) was found useful in separating normal pregnancy, HM, and CA from each other. In choriocarcinoma (CC), reduced excretion was observed in both fraction 1 and fraction 2 steroids. The linear relationship between the logarithm of fraction 2-fraction 1 ratio and that of pregnanediol excretion, as observed in the reproductive cycle of a healthy woman, was not detectable in women with CA, whose urine revealed a low value of log (fraction 2/fraction 1) in spite of an abundant HCG content. It is indicated that the above findings reflect the deficiency of ovarian steroidogenesis under the influence of abnormal HCG from tumors.", "contents": "The value of urinary steroid analysis in chorionic neoplasia. The profile of urinary neutral steroids was investigated in normal pregnancy and chorionic neoplasia by gas-liquid chromatography. The whole chramatogram was divided into three metabolically distinct fractions. The excretion of fraction 2, including four menstruation-dependent steroids (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, and pregnanetrial), was remarkably increased in normal pregnancy as compared with that in nonpregnant controls. But the same parameter was differentially reduced in hydatidiform mole (HM) and chorioadenoma destruens (CA) as compared with normal pregnancy, and the ratio of fraction 2 to fraction 1 (11-deoxy-17-ketosteroids) was found useful in separating normal pregnancy, HM, and CA from each other. In choriocarcinoma (CC), reduced excretion was observed in both fraction 1 and fraction 2 steroids. The linear relationship between the logarithm of fraction 2-fraction 1 ratio and that of pregnanediol excretion, as observed in the reproductive cycle of a healthy woman, was not detectable in women with CA, whose urine revealed a low value of log (fraction 2/fraction 1) in spite of an abundant HCG content. It is indicated that the above findings reflect the deficiency of ovarian steroidogenesis under the influence of abnormal HCG from tumors."}
{"id": "PMID:190890", "title": "Ultrastructure of a polysome-lamellae complex in a human paraganglioma.", "content": "Study of a human abdominal paraganglioma under electron microscopy revealed an unusual cytoplasmic inclusion appearing as a hollow cylinder made up of one or several concentric lamellae surrounded by single or aggregated granules. Cross sections of the lamellar element show a discontinuous juxtaposition of particles. It is moderately dense and is bordered by 140--to 250-A granules of sure ribosomal nature. The inclusion is closely connected to the rough endoplasmic reticulum. The origin and significance of this complex are discussed.", "contents": "Ultrastructure of a polysome-lamellae complex in a human paraganglioma. Study of a human abdominal paraganglioma under electron microscopy revealed an unusual cytoplasmic inclusion appearing as a hollow cylinder made up of one or several concentric lamellae surrounded by single or aggregated granules. Cross sections of the lamellar element show a discontinuous juxtaposition of particles. It is moderately dense and is bordered by 140--to 250-A granules of sure ribosomal nature. The inclusion is closely connected to the rough endoplasmic reticulum. The origin and significance of this complex are discussed."}
{"id": "PMID:190891", "title": "Pulmonary carcinoma (Jaagsiekte) of sheep. Ultrastructural study of early and advanced tumor lesions.", "content": "Lung carcinoma of sheep (Jaagsiekte) is a bronchiolar-alveolar cell carcinoma. Differences in the ultrastructural patterns of early and advanced lesions of the disease are described. A-type and C-type viruses were observed in advanced tumors and were absent in early lesions. Numerous microtubules were characteristic in the epithelial tumor cells of the early lesions and were absent in the advanced tumor. In comparison to the early lesions, extensive cytosome production, surfactant secretion, and glycogen accumulation were observed in the advanced tumor. The immune response to the early tumor lesion was restricted to the peribronchiolar lymph aggregates, while in the advanced stages of the disease the systemic immune response was markedly increased.", "contents": "Pulmonary carcinoma (Jaagsiekte) of sheep. Ultrastructural study of early and advanced tumor lesions. Lung carcinoma of sheep (Jaagsiekte) is a bronchiolar-alveolar cell carcinoma. Differences in the ultrastructural patterns of early and advanced lesions of the disease are described. A-type and C-type viruses were observed in advanced tumors and were absent in early lesions. Numerous microtubules were characteristic in the epithelial tumor cells of the early lesions and were absent in the advanced tumor. In comparison to the early lesions, extensive cytosome production, surfactant secretion, and glycogen accumulation were observed in the advanced tumor. The immune response to the early tumor lesion was restricted to the peribronchiolar lymph aggregates, while in the advanced stages of the disease the systemic immune response was markedly increased."}
{"id": "PMID:190893", "title": "Excitation conduction in Meissner's plexus of rabbit small intestine.", "content": "Excitation conduction in Meissner's plexus of the rabit small intestine was investigated by analyzing the records of potentials evoked by a single electrical stimulus applied to this plexus. Experiments were performed on the Meissner's plexus that remained attached to the circular muscle after the longitudinal muscle and mucous membrane were removed from intestinal segment. Conduction velocities of nerve impulses were 0.3-0.7 m/s, chronaxie of the nerve bundle was 0.06-0.12 ms. While the distance between the stimulating and recording electrodes was increased, the latency of evoked potentials was prolonged, the number increased, and the amplitude decreased; no potentials could be recorded when the distance  was more than 4 mm. Evoked potentials recorded at relatively long conduction distance were reduced in amplitude or abolished after a repeated stimulation with high frequencies above 50/s, after hexamethonium application, and in a state of lack of oxygen. It was concluded that, in Meissner's plexus, nerve impulses spread through multiple pathways and make synaptic transmission at a relatively short conduction distance.", "contents": "Excitation conduction in Meissner's plexus of rabbit small intestine. Excitation conduction in Meissner's plexus of the rabit small intestine was investigated by analyzing the records of potentials evoked by a single electrical stimulus applied to this plexus. Experiments were performed on the Meissner's plexus that remained attached to the circular muscle after the longitudinal muscle and mucous membrane were removed from intestinal segment. Conduction velocities of nerve impulses were 0.3-0.7 m/s, chronaxie of the nerve bundle was 0.06-0.12 ms. While the distance between the stimulating and recording electrodes was increased, the latency of evoked potentials was prolonged, the number increased, and the amplitude decreased; no potentials could be recorded when the distance  was more than 4 mm. Evoked potentials recorded at relatively long conduction distance were reduced in amplitude or abolished after a repeated stimulation with high frequencies above 50/s, after hexamethonium application, and in a state of lack of oxygen. It was concluded that, in Meissner's plexus, nerve impulses spread through multiple pathways and make synaptic transmission at a relatively short conduction distance."}
{"id": "PMID:190894", "title": "Glucose-stimulated and La3+-nondisplaceable Ca2+ pool in pancreatic islets.", "content": "To study intracellular pools of calcium tissue specimens from noninbred ob/ob mice were labeled with 45Ca2+ and subsequently washed with La3+. D-glucose, 20 mM, enhanced the labeling of the La3+-nondisplaceable calcium in pancreatic islets but not in pieces of exocrine pancreas or liver. The disappearance of 45Ca2+ from labeled islets was accelerated by the ionophore, X-537A, but not by dibutyryl cyclic AMP, theophylline, or pentobarbital. On fractionation of 45Ca2+-labeled islets, the greatest radioactivity per unit of protein occured in a fraction rich in insulin secretory granules. The radioactivity of this fraction was higher after the islets had been loaded with 45Ca2+ in the presence of 20 mM glucose as compared to 3 mM glucose. It is concluded that the secretory granules make up a considerable part of the glucose-sensitive calcium store in the beta-cells.", "contents": "Glucose-stimulated and La3+-nondisplaceable Ca2+ pool in pancreatic islets. To study intracellular pools of calcium tissue specimens from noninbred ob/ob mice were labeled with 45Ca2+ and subsequently washed with La3+. D-glucose, 20 mM, enhanced the labeling of the La3+-nondisplaceable calcium in pancreatic islets but not in pieces of exocrine pancreas or liver. The disappearance of 45Ca2+ from labeled islets was accelerated by the ionophore, X-537A, but not by dibutyryl cyclic AMP, theophylline, or pentobarbital. On fractionation of 45Ca2+-labeled islets, the greatest radioactivity per unit of protein occured in a fraction rich in insulin secretory granules. The radioactivity of this fraction was higher after the islets had been loaded with 45Ca2+ in the presence of 20 mM glucose as compared to 3 mM glucose. It is concluded that the secretory granules make up a considerable part of the glucose-sensitive calcium store in the beta-cells."}
{"id": "PMID:190895", "title": "Prostaglandins in adrenergic transmission of isolated perfused rat pancreas.", "content": "In the isolated, perfused rat pancreas, prostaglandins (PGs) E1 and E2 1-5 ng/ml, reduced the vasoconstrictor responses to periarterial nerve stimulation and variably affected those to injected norepinephrine. Prostaglandin F2alpha had no consistent effect on the vasoconstrictor responses to both adrenergic stimuli. Stimulation of adrenergic nerves or administration of norepinephrine released a PGE-like substance from  the perfused pancreas which was abolished by inhibitors of PG synthesis, acetylsalicylic acid, indomethacin, meclofenamate, and eicosa-5,8,11,14-tetraynoic acid. The latter three agents did not potentiate, but rather reduced the vasoconstrictor responses to both adrenergic stimuli. Arachidonic acid that was converted by the pancreas into PGE2 and PGF2alpha inhibited the vasoconstrictor responses to adrenergic stimuli. The latter effect of arachidonic acid was not altered by the simultaneous infusion of PG synthetase inhibitors. Although these results, which could be attributed to a direct effect of inhibitors of PG synthesis and arachidonic acid on adrenergic neuroeffector junction, fail to establish the role of endogenous PGs in modulating adrenergic responses in rat pancreatic vessels, they emphasize the differences in the effect of PGE1 and PGE2 on adrenergic responses in various vascular beds of the rat.", "contents": "Prostaglandins in adrenergic transmission of isolated perfused rat pancreas. In the isolated, perfused rat pancreas, prostaglandins (PGs) E1 and E2 1-5 ng/ml, reduced the vasoconstrictor responses to periarterial nerve stimulation and variably affected those to injected norepinephrine. Prostaglandin F2alpha had no consistent effect on the vasoconstrictor responses to both adrenergic stimuli. Stimulation of adrenergic nerves or administration of norepinephrine released a PGE-like substance from  the perfused pancreas which was abolished by inhibitors of PG synthesis, acetylsalicylic acid, indomethacin, meclofenamate, and eicosa-5,8,11,14-tetraynoic acid. The latter three agents did not potentiate, but rather reduced the vasoconstrictor responses to both adrenergic stimuli. Arachidonic acid that was converted by the pancreas into PGE2 and PGF2alpha inhibited the vasoconstrictor responses to adrenergic stimuli. The latter effect of arachidonic acid was not altered by the simultaneous infusion of PG synthetase inhibitors. Although these results, which could be attributed to a direct effect of inhibitors of PG synthesis and arachidonic acid on adrenergic neuroeffector junction, fail to establish the role of endogenous PGs in modulating adrenergic responses in rat pancreatic vessels, they emphasize the differences in the effect of PGE1 and PGE2 on adrenergic responses in various vascular beds of the rat."}
{"id": "PMID:190896", "title": "Ileal mucosal cyclic AMP and Cl secretion: serosal vs. mucosal addition of cholera toxin.", "content": "Changes in ion transport and cyclic AMP (cAMP) concentration produced by addition of cholera toxin to the serosal side of isolated rabbit ileal mucosa (CTs) were compared to the changes produced by addition to the mucosal side (CTm). CTs increased short-circuit current (SCC) as did CTm but it did so more slowly. CTs, unlike CTm, did not significantly decrease electrical conductance. Inhibition of the  SCC response to theophylline, a measure of preexisting secretion, was almost complete 180 min after CTm but was not yet significant 180 min after CTs. Longer (280 min) after CTs, the SCC response to theophylline was reduced by 59%, a significant reduction but less than that caused by CTm. A statistically significant change in net Cl flux could not be demonstrated after CTs, although at 280 min the measured flux was halfway between the fluxes for control and CTm tissues. Cyclic AMP concentrations were determined at 190 min, 10 min after addition of theophylline. CTs, despite little or no effect on ion transport, increased cAMP to the same level as did CTm, and the effect on cAMP of adding toxin to both sides was additive. We conclude that 1) active secretion is  probably stimulated by cholera toxin added on the serosal side, although more slowly than after addition to the mucosal side and 2) much of the toxin-stimulated cAMP content of the mucosa is not coupled to secretion.", "contents": "Ileal mucosal cyclic AMP and Cl secretion: serosal vs. mucosal addition of cholera toxin. Changes in ion transport and cyclic AMP (cAMP) concentration produced by addition of cholera toxin to the serosal side of isolated rabbit ileal mucosa (CTs) were compared to the changes produced by addition to the mucosal side (CTm). CTs increased short-circuit current (SCC) as did CTm but it did so more slowly. CTs, unlike CTm, did not significantly decrease electrical conductance. Inhibition of the  SCC response to theophylline, a measure of preexisting secretion, was almost complete 180 min after CTm but was not yet significant 180 min after CTs. Longer (280 min) after CTs, the SCC response to theophylline was reduced by 59%, a significant reduction but less than that caused by CTm. A statistically significant change in net Cl flux could not be demonstrated after CTs, although at 280 min the measured flux was halfway between the fluxes for control and CTm tissues. Cyclic AMP concentrations were determined at 190 min, 10 min after addition of theophylline. CTs, despite little or no effect on ion transport, increased cAMP to the same level as did CTm, and the effect on cAMP of adding toxin to both sides was additive. We conclude that 1) active secretion is  probably stimulated by cholera toxin added on the serosal side, although more slowly than after addition to the mucosal side and 2) much of the toxin-stimulated cAMP content of the mucosa is not coupled to secretion."}
{"id": "PMID:190897", "title": "Effects of high potassium concentration on theophylline responses of toad bladder.", "content": "It has been demonstrated previously that a high concentration of potassium in the serosal bathing medium (5-21.5 mM) potentiates the increase in short-circuit current caused by vasopressin or exogenous cyclic AMP. The same concentration of potassium in the bathing medium inhibited the increase in short-circuit current caused by theophylline. The increases in osmotic water permeability caused by vasopressin or cyclic AMP were unaffected by a serosal potassium concentration of 21.5 mM. The increase in osmotic water permeability caused by theophylline was inhibited by 21.5 mM potassium. The concentration of cyclic AMP in either intact total bladder or isolated toad bladder cells was increased two- or three-fold by theophylline. Increasing the concentration of potassium to 21.5 mM did not alter cyclic AMP concentration in either the absence of presence of theophylline. One interpretation of these results is that theophylline increases osmotic water flow and short-circuit current by a mechanism other than by inhibition of cyclic nucleotide phosphodiesterase.", "contents": "Effects of high potassium concentration on theophylline responses of toad bladder. It has been demonstrated previously that a high concentration of potassium in the serosal bathing medium (5-21.5 mM) potentiates the increase in short-circuit current caused by vasopressin or exogenous cyclic AMP. The same concentration of potassium in the bathing medium inhibited the increase in short-circuit current caused by theophylline. The increases in osmotic water permeability caused by vasopressin or cyclic AMP were unaffected by a serosal potassium concentration of 21.5 mM. The increase in osmotic water permeability caused by theophylline was inhibited by 21.5 mM potassium. The concentration of cyclic AMP in either intact total bladder or isolated toad bladder cells was increased two- or three-fold by theophylline. Increasing the concentration of potassium to 21.5 mM did not alter cyclic AMP concentration in either the absence of presence of theophylline. One interpretation of these results is that theophylline increases osmotic water flow and short-circuit current by a mechanism other than by inhibition of cyclic nucleotide phosphodiesterase."}
{"id": "PMID:190898", "title": "Identification of smooth muscle series elastic component in intact carotid artery.", "content": "Experiments were performed to indentify the series elastic component (SEC) in intact dog carotid artery held at in situ length. The vessels were studied during excitation of the muscle with norepinephrine and after metabolic poisoning with potassium cyanide and sodium iodoacetate. Static circumferential stress-strain curves and stress-quick-release stiffness curves were examined to evaluate Maxwell and Voigt model elements. The vessels were studied at 33, 36, and 39 degrees C. Temperature variations altered active stress, but did not alter connective tissue properties or the Maxwell SEC stiffness. The Voigt model SEC stiffness was altered, but this was secondary to changes in active stress. Thus, most of the SEC is separate from the contractile apparatus. Other vessels were treated with elastase, collagenase, or hyaluronidase to digest the connective tissue components of the wall. Hyaluronidase had no effect on mechanics. Elastase and collagenase altered connective tissue properties, but only elastase unequivocally altered SEC stiffness. This analysis indicated 1) that the carotid artery wall is better represented by a Maxwell model than a Voigt model, and 2) that the SEC in intact carotid artery is primarily elastin.", "contents": "Identification of smooth muscle series elastic component in intact carotid artery. Experiments were performed to indentify the series elastic component (SEC) in intact dog carotid artery held at in situ length. The vessels were studied during excitation of the muscle with norepinephrine and after metabolic poisoning with potassium cyanide and sodium iodoacetate. Static circumferential stress-strain curves and stress-quick-release stiffness curves were examined to evaluate Maxwell and Voigt model elements. The vessels were studied at 33, 36, and 39 degrees C. Temperature variations altered active stress, but did not alter connective tissue properties or the Maxwell SEC stiffness. The Voigt model SEC stiffness was altered, but this was secondary to changes in active stress. Thus, most of the SEC is separate from the contractile apparatus. Other vessels were treated with elastase, collagenase, or hyaluronidase to digest the connective tissue components of the wall. Hyaluronidase had no effect on mechanics. Elastase and collagenase altered connective tissue properties, but only elastase unequivocally altered SEC stiffness. This analysis indicated 1) that the carotid artery wall is better represented by a Maxwell model than a Voigt model, and 2) that the SEC in intact carotid artery is primarily elastin."}
{"id": "PMID:190899", "title": "Cyclic nucleotide metabolism and vasodilation in canine mesenteric artery.", "content": "The uptake and extracellular and intracellular metabolism of radioisotopically labeled cyclic 3',5'-adenosine monophosphate (cAMP) and dibutyryl cAMP (DBcAMP) was determined in canine mesenteric arteries incubated in vitro. Intracellular tissue uptake was measured by radioisotope counting and labeled metabolites separated by thin-layer chromatography. Extracellularly, cAMP was extensively metabolized to AMP, adenosine, and Pi. DBcAMP was metabolized to monobutyryl cAMP (MBcAMP) intracellularly. Vasodilation of the mesenteric circulation in vivo was produced by cAMP, its metabolites and DBcAMP. DBcAMP caused greater vasodilation than cAMP but had a response time to its peak effect of 12 min versus 90 s for cAMP. The vasodilator properties of cAMP and DBcAMP were related to their metabolism. It was concluded that the vasodilation caused by cAMP was due to cAMP metabolites produced by extracellular metabolism.", "contents": "Cyclic nucleotide metabolism and vasodilation in canine mesenteric artery. The uptake and extracellular and intracellular metabolism of radioisotopically labeled cyclic 3',5'-adenosine monophosphate (cAMP) and dibutyryl cAMP (DBcAMP) was determined in canine mesenteric arteries incubated in vitro. Intracellular tissue uptake was measured by radioisotope counting and labeled metabolites separated by thin-layer chromatography. Extracellularly, cAMP was extensively metabolized to AMP, adenosine, and Pi. DBcAMP was metabolized to monobutyryl cAMP (MBcAMP) intracellularly. Vasodilation of the mesenteric circulation in vivo was produced by cAMP, its metabolites and DBcAMP. DBcAMP caused greater vasodilation than cAMP but had a response time to its peak effect of 12 min versus 90 s for cAMP. The vasodilator properties of cAMP and DBcAMP were related to their metabolism. It was concluded that the vasodilation caused by cAMP was due to cAMP metabolites produced by extracellular metabolism."}
{"id": "PMID:190900", "title": "A bone matrix calcification-initiator noncollagenous protein.", "content": "When completely demineralized, the densely packed structure of bone matrix does not recalcify, neither in physiologic solutions in vitro nor in implants in vivo. Even when inorganic and organic calcification inhibitors (which normally are stored in bone matrix) are removed first by autolytic digestion in neutral buffers at 37C and then by sequential chemical extraction, implants of the EDTA insoluble residue will not recalcify after as long as 4 wk in a muscle pouch. However, if first demineralized in cold dilute HCl, second, extracted and autodigested in buffers solution at 37C, and then further extracted in EDTA and other solutions at 2C, a calcification initiator protein (Cp) is unmasked, and the residue will invariable recalcify. CIP, isolated by gel filtration and column chromatography, is a disulfide-bonded glycoprotein aggregate composed of subunites of a moleclar mass of 55,000. CIP is composed of a large proportion of acidic amino acids and has a calcium binding capacity of about 1.8 times greater than albumin. The affinity constant CaCIP, calculated by ultrafiltration of physiologic solutions of Ca2+, is log K, 2.9. Observations on implants of residues that containe a) CIP but not a bone morphogenetic property (BMP), B) BMP accompanied by CIP activity, or c) neither BMP nor CIP activity suggested that BMP covers CIP and that the two are attached to bone collagen in tandem. Whether CIP plays a part in calcification of the normal skeleton requires further investigation.", "contents": "A bone matrix calcification-initiator noncollagenous protein. When completely demineralized, the densely packed structure of bone matrix does not recalcify, neither in physiologic solutions in vitro nor in implants in vivo. Even when inorganic and organic calcification inhibitors (which normally are stored in bone matrix) are removed first by autolytic digestion in neutral buffers at 37C and then by sequential chemical extraction, implants of the EDTA insoluble residue will not recalcify after as long as 4 wk in a muscle pouch. However, if first demineralized in cold dilute HCl, second, extracted and autodigested in buffers solution at 37C, and then further extracted in EDTA and other solutions at 2C, a calcification initiator protein (Cp) is unmasked, and the residue will invariable recalcify. CIP, isolated by gel filtration and column chromatography, is a disulfide-bonded glycoprotein aggregate composed of subunites of a moleclar mass of 55,000. CIP is composed of a large proportion of acidic amino acids and has a calcium binding capacity of about 1.8 times greater than albumin. The affinity constant CaCIP, calculated by ultrafiltration of physiologic solutions of Ca2+, is log K, 2.9. Observations on implants of residues that containe a) CIP but not a bone morphogenetic property (BMP), B) BMP accompanied by CIP activity, or c) neither BMP nor CIP activity suggested that BMP covers CIP and that the two are attached to bone collagen in tandem. Whether CIP plays a part in calcification of the normal skeleton requires further investigation."}
{"id": "PMID:190901", "title": "New method of quantifying ligand binding based on measurement of an induced response.", "content": "A new general method is proposed for quantifying ligand-receptor interactions using the biological response induced by the ligand as an index of ligand binding. With this method the binding of human chorionic gonadotropin (hCG), several hCG derivatives, and luteinizing hormone (LH) to rat Leydig cells was measured by analysis of the ability of these materials to stimulate testosterone formation. As applied here, hormone dose-response curves were generated in the presence of increasing numbers of cells incubated in vitro in a successful attempt to alter the concentrations of bound and free hormone in the incubation mixture. Measurements of testosterone synthesis as a function of the total amounts of hormone and numbers of cells enabled us to evaluate the concentrations of both bound and free hormone at any constant fractional response (i.e. quarter-, half-, or three-quarter-maximal). We were thus able to measure hormone binding at the extremely low hormone concentrations (1 pM) within the steroidogenic dose-response range under conditions that would not have been possible using currently available radioiodinated hCG preparations. The results obrained confirmed the presence of spare functional receptors. Specific quantitative results are discussed in the text.", "contents": "New method of quantifying ligand binding based on measurement of an induced response. A new general method is proposed for quantifying ligand-receptor interactions using the biological response induced by the ligand as an index of ligand binding. With this method the binding of human chorionic gonadotropin (hCG), several hCG derivatives, and luteinizing hormone (LH) to rat Leydig cells was measured by analysis of the ability of these materials to stimulate testosterone formation. As applied here, hormone dose-response curves were generated in the presence of increasing numbers of cells incubated in vitro in a successful attempt to alter the concentrations of bound and free hormone in the incubation mixture. Measurements of testosterone synthesis as a function of the total amounts of hormone and numbers of cells enabled us to evaluate the concentrations of both bound and free hormone at any constant fractional response (i.e. quarter-, half-, or three-quarter-maximal). We were thus able to measure hormone binding at the extremely low hormone concentrations (1 pM) within the steroidogenic dose-response range under conditions that would not have been possible using currently available radioiodinated hCG preparations. The results obrained confirmed the presence of spare functional receptors. Specific quantitative results are discussed in the text."}
{"id": "PMID:190902", "title": "Lipoprotein lipase distribution in rat adipose tissues: effect on chylomicron uptake.", "content": "Adipocytes in the epididymal (Epi) and perirenal (PR) depots of the rat increased continuously in size in rats ranging fromm 50 to 550  g body wt. In contrast, cell size in the subcutaneous (SC) and mesenteric (M) depots was similar to that in the other two depots only until rats achieved 250-350 g. Thereafter, adipocytes in the latter depots were significantly smaller than in the former. In all four depots, the activity of lipoprotein lipase (LPL) per 10(6) cells increased with increasing size in both fed and fasted rats. No significant differences were noted in LPL activity per 10(6) cells between depots as a function of cell size in either nutritional state. During growth, a greater percentage of whole tissue LPL of all depots was sequestered within enlarging adipocytes, resulting in an absolute decrease in activity extracellulalrly. This effect was least pronounced in the Epi and PR depots. In large adipocytes of fed rats, decreased extracellular localization of LPL was paralleled in vivo by decreased uptake of chylomicron triglyceride fatty acids in all depots. In fasted rats, uptake was low and unaffected by changes in cell size in all sites.", "contents": "Lipoprotein lipase distribution in rat adipose tissues: effect on chylomicron uptake. Adipocytes in the epididymal (Epi) and perirenal (PR) depots of the rat increased continuously in size in rats ranging fromm 50 to 550  g body wt. In contrast, cell size in the subcutaneous (SC) and mesenteric (M) depots was similar to that in the other two depots only until rats achieved 250-350 g. Thereafter, adipocytes in the latter depots were significantly smaller than in the former. In all four depots, the activity of lipoprotein lipase (LPL) per 10(6) cells increased with increasing size in both fed and fasted rats. No significant differences were noted in LPL activity per 10(6) cells between depots as a function of cell size in either nutritional state. During growth, a greater percentage of whole tissue LPL of all depots was sequestered within enlarging adipocytes, resulting in an absolute decrease in activity extracellulalrly. This effect was least pronounced in the Epi and PR depots. In large adipocytes of fed rats, decreased extracellular localization of LPL was paralleled in vivo by decreased uptake of chylomicron triglyceride fatty acids in all depots. In fasted rats, uptake was low and unaffected by changes in cell size in all sites."}
{"id": "PMID:190903", "title": "Kinetic analysis of iodide transport in dog thyroid slices: perchlorate-induced discharge.", "content": "Dog thyroid slices were incubated with methimazole (2 mM) and radioiodide. The medium radioactivity was continuously recorded for 8 h. Multiple data were collected for individual glands to calculate simultaneously by compartmental analysis the influx and efflux rates of iodide from the slices. A two-compartment thyroid model was necessary and sufficient to simulate the transport of inorganic iodide. The two compartments could be defined as the cellular and the luminal spaces, but interferences due to slice thickness, nonuniform follicle sizes, and open follicles were not excluded. Sodium perchlorate (1 mM) inhibited the influx of iodide into the follicles and discharged the trapped radioiode into the medium with increased efflux rates. Our data suggest that perchlorate decreases the inward influx rates by competition and enhances the outward efflux rates by countertransport and support the hypothesis of mobile iodide carriers at the basal and apical membranes of the thyroid cells.", "contents": "Kinetic analysis of iodide transport in dog thyroid slices: perchlorate-induced discharge. Dog thyroid slices were incubated with methimazole (2 mM) and radioiodide. The medium radioactivity was continuously recorded for 8 h. Multiple data were collected for individual glands to calculate simultaneously by compartmental analysis the influx and efflux rates of iodide from the slices. A two-compartment thyroid model was necessary and sufficient to simulate the transport of inorganic iodide. The two compartments could be defined as the cellular and the luminal spaces, but interferences due to slice thickness, nonuniform follicle sizes, and open follicles were not excluded. Sodium perchlorate (1 mM) inhibited the influx of iodide into the follicles and discharged the trapped radioiode into the medium with increased efflux rates. Our data suggest that perchlorate decreases the inward influx rates by competition and enhances the outward efflux rates by countertransport and support the hypothesis of mobile iodide carriers at the basal and apical membranes of the thyroid cells."}
{"id": "PMID:190904", "title": "Renin stimulation by isoproterenol and theophylline in the isolated perfused kidney.", "content": "The intrarenal mechanisms of renin release were studied in the isolated perfused rabbit kidney during stimulation by isoproterenol, 0.01 mug/kg per min, and by theophylline, 0.87 mg/kg per min. In the absence of urinary flow during the early stages of perfusion, isoproterenol caused a 17% increase of renal vein serum renin concentration (RVSRC) (P less than 0.001) without changing renal blood flow, renal vascular resistance, or serum potassium. dl-Propranolol, 2.0 mg/kg per min. abolished this isoproterenol-induced renin release. A moderate reduction in perfusion pressure prior to the infusion of isoproterenol resulted in a marked additional stimulation of renin release. Studies during and following ureteral occlusion demonstrated that theophylline stimulates renin release by decreasing renal vascular resistance, whereas the concomitant increase in sodium transport to the macula densa exerted an opposite effect. dl-Propranolol did not affect theophylline-induced renin secretion. It is concluded that single exogenous stimuli may activate more than one intrarenal mechanism simultaneously. Isoproterenol has a direct renin-stimulatory effect on intrarenal beta-adrenergic receptors that may be reinforced by baroreceptor stimulation. Theophylline stimulates renin via a baroreceptor mechanism, with simultaneous renin suppression via a sodium-macula densa effect.", "contents": "Renin stimulation by isoproterenol and theophylline in the isolated perfused kidney. The intrarenal mechanisms of renin release were studied in the isolated perfused rabbit kidney during stimulation by isoproterenol, 0.01 mug/kg per min, and by theophylline, 0.87 mg/kg per min. In the absence of urinary flow during the early stages of perfusion, isoproterenol caused a 17% increase of renal vein serum renin concentration (RVSRC) (P less than 0.001) without changing renal blood flow, renal vascular resistance, or serum potassium. dl-Propranolol, 2.0 mg/kg per min. abolished this isoproterenol-induced renin release. A moderate reduction in perfusion pressure prior to the infusion of isoproterenol resulted in a marked additional stimulation of renin release. Studies during and following ureteral occlusion demonstrated that theophylline stimulates renin release by decreasing renal vascular resistance, whereas the concomitant increase in sodium transport to the macula densa exerted an opposite effect. dl-Propranolol did not affect theophylline-induced renin secretion. It is concluded that single exogenous stimuli may activate more than one intrarenal mechanism simultaneously. Isoproterenol has a direct renin-stimulatory effect on intrarenal beta-adrenergic receptors that may be reinforced by baroreceptor stimulation. Theophylline stimulates renin via a baroreceptor mechanism, with simultaneous renin suppression via a sodium-macula densa effect."}
{"id": "PMID:190905", "title": "Pharmacological analysis of sympathetic function in the embryonic chick heart.", "content": "Sympathetic nerve cells enter the embryonic chick heart on the fifth day in ovo, but it is uncertain when these nerves become functional. Using pharmacological probes known to affect the embryonic circulation, sympathetic nerve function was examined at various stages of development. Exogenous norepinephrine elicited cardioacceleration in the hearts of embryos with intact extraembryonic circulation both before (stage 20-24) and after (stage 28-32) sympathetic innervation of the heart, and this acceleration could be inhibited by propranolol and practolol. In contrast, ganglionic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) elicited cardioacceleration only after stages 27-28 (i.e., after sympathetic innervation), producing a 25-30% increase in heart rate over the predrug levels of 148.7 +/- 1.8 beats/min. DMPP-elicited positive chronotropy was reduced by beta-receptor antagonists, hexamethonium, guanethidine (GuE), and tetrodotoxin. In preparations of the embryonic thorax in which the innervated heart was separated from brain and adrenal influences, DMPP elicited a GuE-sensitive cardioacceleration. It is concluded that during chick embryonic development, no more than a 1-day interval exists between the appearance of sympathetic nerves in the heart and the onset of neuronal function in that organ.", "contents": "Pharmacological analysis of sympathetic function in the embryonic chick heart. Sympathetic nerve cells enter the embryonic chick heart on the fifth day in ovo, but it is uncertain when these nerves become functional. Using pharmacological probes known to affect the embryonic circulation, sympathetic nerve function was examined at various stages of development. Exogenous norepinephrine elicited cardioacceleration in the hearts of embryos with intact extraembryonic circulation both before (stage 20-24) and after (stage 28-32) sympathetic innervation of the heart, and this acceleration could be inhibited by propranolol and practolol. In contrast, ganglionic stimulation with 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) elicited cardioacceleration only after stages 27-28 (i.e., after sympathetic innervation), producing a 25-30% increase in heart rate over the predrug levels of 148.7 +/- 1.8 beats/min. DMPP-elicited positive chronotropy was reduced by beta-receptor antagonists, hexamethonium, guanethidine (GuE), and tetrodotoxin. In preparations of the embryonic thorax in which the innervated heart was separated from brain and adrenal influences, DMPP elicited a GuE-sensitive cardioacceleration. It is concluded that during chick embryonic development, no more than a 1-day interval exists between the appearance of sympathetic nerves in the heart and the onset of neuronal function in that organ."}
{"id": "PMID:190907", "title": "Disulfiram toxicity and carbon disulfide poisoning.", "content": "The author compared the neurotoxic effects of disulfiram with those of carbon disulfide, a disulfiram metabolite. The results suggest that carbon disulfide is responsible for the behavioral and neurological side effects of disulfiram. If this is so, then some other toxic effects of carbon disulfide, including parkinsonism, choreoathetosis, and thalamic syndrome may follow the ingestion of more than 5 g of disulfiram by adults, and individuals receiving as little as 125 mg of disulfiram per day may be at a three- to four-fold greater risk for arteriosclerotic cardiovascular disease than a comparable population not receiving the drug.", "contents": "Disulfiram toxicity and carbon disulfide poisoning. The author compared the neurotoxic effects of disulfiram with those of carbon disulfide, a disulfiram metabolite. The results suggest that carbon disulfide is responsible for the behavioral and neurological side effects of disulfiram. If this is so, then some other toxic effects of carbon disulfide, including parkinsonism, choreoathetosis, and thalamic syndrome may follow the ingestion of more than 5 g of disulfiram by adults, and individuals receiving as little as 125 mg of disulfiram per day may be at a three- to four-fold greater risk for arteriosclerotic cardiovascular disease than a comparable population not receiving the drug."}
{"id": "PMID:190908", "title": "Analysis of clinically occult and mammographically occult breast tumors.", "content": "Findings by xeromammography and clinical examination were compared in 16,000 self-selected women aged 45-64 who participated in a voluntary breast cancer screening program. A total of 138 malignancies were detected: 108 (78%) by mammography and 78 (57%) by clinical examination. Mammography was more effective for large breasts, fatty breasts, and in older women. Conversely, clinical examination was more effective for small breasts, dense breasts, and retroareolar lesions. Clinical detection decreased strikingly for lesions with negative lymph nodes, in situ and microinvasive lesions, deeply situated lesions, and lesions where microcalcifications were the sole mammographic finding.", "contents": "Analysis of clinically occult and mammographically occult breast tumors. Findings by xeromammography and clinical examination were compared in 16,000 self-selected women aged 45-64 who participated in a voluntary breast cancer screening program. A total of 138 malignancies were detected: 108 (78%) by mammography and 78 (57%) by clinical examination. Mammography was more effective for large breasts, fatty breasts, and in older women. Conversely, clinical examination was more effective for small breasts, dense breasts, and retroareolar lesions. Clinical detection decreased strikingly for lesions with negative lymph nodes, in situ and microinvasive lesions, deeply situated lesions, and lesions where microcalcifications were the sole mammographic finding."}
{"id": "PMID:190909", "title": "Effect of insecticide spraying for malaria control on the incidence of sandfly fever in Athens, Greece.", "content": "Sera from 637 Athens residents of various age groups were examined by plaque reduction neutralization test for antibodies against Naples and Sicilian Phlebotomus fever viruses. A marked change in the prevalence of antibodies to both agents was observed in persons born after 1946, when residual insecticide spraying for malaria control was initiated in Greece. The prevalence of Naples and Sicilian neutralizing antibodies among residents greater than or equal to 30 years of age was 36% and 13%, respectively. In contrast, only 4% of persons less than or equal to 29 years of age had Naples antibodies and all were negative to Sicilian. These serologic data confirm previous clinical observations that sandfly fever becam uncommon in Athens after initiation of the insecticide spraying program. Presumedly the spraying program was effective in reducing the Phlebotomus population to levels where virus transmission was minimal. New information on the specificity and duration of Phlebotomus fever neutralizing antibodies is also presented.", "contents": "Effect of insecticide spraying for malaria control on the incidence of sandfly fever in Athens, Greece. Sera from 637 Athens residents of various age groups were examined by plaque reduction neutralization test for antibodies against Naples and Sicilian Phlebotomus fever viruses. A marked change in the prevalence of antibodies to both agents was observed in persons born after 1946, when residual insecticide spraying for malaria control was initiated in Greece. The prevalence of Naples and Sicilian neutralizing antibodies among residents greater than or equal to 30 years of age was 36% and 13%, respectively. In contrast, only 4% of persons less than or equal to 29 years of age had Naples antibodies and all were negative to Sicilian. These serologic data confirm previous clinical observations that sandfly fever becam uncommon in Athens after initiation of the insecticide spraying program. Presumedly the spraying program was effective in reducing the Phlebotomus population to levels where virus transmission was minimal. New information on the specificity and duration of Phlebotomus fever neutralizing antibodies is also presented."}
{"id": "PMID:190910", "title": "Experimental milk-borne transmission of Powassan virus in the goat.", "content": "A lactating goat with a 74-day-old kid was inoculated with 10(3) mouse 50% lethal dose (LD50) of Powassan virus. No ensuing viremia could be detected, but virus was secreted in the milk on postinoculation days 7 through 15, with a titer of 10(5) LD50/ml on day 12. Neutralizing antibody was found in the serum on days 22 through 36 and in the milk on day 36. The offspring was not inoculated but was allowed to continue feeding on its mother's milk. It developed neutralizing antibody by day 22. Since the kid was past the age when it could resorb antibody from the milk, its serum antibody was evidence of active infection. Neither animal showed any clinical sign of illness. A serum survey of 499 goats in New York State showed that 9 had neutralizing antibodies to Powassan virus. These immune goats came from widely scattered localities, including counties where human cases have been confirmed. The findings suggest the possibility of milk-borne transmission of Powassan virus from goat to man.", "contents": "Experimental milk-borne transmission of Powassan virus in the goat. A lactating goat with a 74-day-old kid was inoculated with 10(3) mouse 50% lethal dose (LD50) of Powassan virus. No ensuing viremia could be detected, but virus was secreted in the milk on postinoculation days 7 through 15, with a titer of 10(5) LD50/ml on day 12. Neutralizing antibody was found in the serum on days 22 through 36 and in the milk on day 36. The offspring was not inoculated but was allowed to continue feeding on its mother's milk. It developed neutralizing antibody by day 22. Since the kid was past the age when it could resorb antibody from the milk, its serum antibody was evidence of active infection. Neither animal showed any clinical sign of illness. A serum survey of 499 goats in New York State showed that 9 had neutralizing antibodies to Powassan virus. These immune goats came from widely scattered localities, including counties where human cases have been confirmed. The findings suggest the possibility of milk-borne transmission of Powassan virus from goat to man."}
{"id": "PMID:190920", "title": "The ependyma of ventriculus mesencephali in golden hamsters.", "content": "The ventriculus mesencephali of golden hamsters protrudes, in the form of a short channel, from the upper wall of the aquaeductus Sylvii in dorsal direction, between the third and fourth ventricle. It is lined with ependymal cells of cubic to cylindrical forms. Some of the ependymal cells possess basal processes. On the cell surface, there are cilia, microvilli and protoplasmatic protrusions. The cells contain relatively few endoplasmatic reticulum, a poorly developed Golgi apparatus, free and bound ribosomes and critiform mitochondria. The cell nuclei have round to oval shapes. Supraependymally, there are homogenous globules and intraventricular nerve fibres. The morphological characteristics of ependyma in the region of ventriculus mesencephali, as well as the close contact of the ependymal cells with capillaries, allow to suppose an active participation of these cells in the exchange of various substances also in this part of the brain ventricle system.", "contents": "The ependyma of ventriculus mesencephali in golden hamsters. The ventriculus mesencephali of golden hamsters protrudes, in the form of a short channel, from the upper wall of the aquaeductus Sylvii in dorsal direction, between the third and fourth ventricle. It is lined with ependymal cells of cubic to cylindrical forms. Some of the ependymal cells possess basal processes. On the cell surface, there are cilia, microvilli and protoplasmatic protrusions. The cells contain relatively few endoplasmatic reticulum, a poorly developed Golgi apparatus, free and bound ribosomes and critiform mitochondria. The cell nuclei have round to oval shapes. Supraependymally, there are homogenous globules and intraventricular nerve fibres. The morphological characteristics of ependyma in the region of ventriculus mesencephali, as well as the close contact of the ependymal cells with capillaries, allow to suppose an active participation of these cells in the exchange of various substances also in this part of the brain ventricle system."}
{"id": "PMID:190921", "title": "Antagonism of general anesthesia by naloxone in the rat.", "content": "The effect of naloxone, a narcotic antagonist, on the response of animals to painful stimuli during anesthesia was studied. Rats were anesthetized with cyclopropane, halothane, or enflurane in groups of 12. Following induction, inspired anesthetic concentration was gradually reduced to a point at which 35-60 per cent of animals responded to tail clamping. Thereafter the anesthetic concentration was held constant for 30 minutes. Rats in each group then received saline solution or naloxone, 10mg/kg, given intravenously. The response to tail clamping was retested 5 minutes later. In additional experiments EEG's were recorded from rats anesthesized with one of these anesthetics. After a stable light plane of anesthesia had been attained, each animal was given naloxone, 10 mg/kg, iv, and the EEG recorded for an additional 5 minutes. In the tail-clamping experiments, naloxone approximately doubled the number of rats responding during cyclopropane, halothane, or enflurane anesthesia. The EEG patterns of several animals anesthetized with either cyclopropane or halothane changed to patterns consistent with lighter planes of anesthesia after naloxone administration. That naloxone alters the depth of inhalational anesthesia suggests that anesthetics may release an endogenous morphine-like factor (MLF) in the central nervous system.", "contents": "Antagonism of general anesthesia by naloxone in the rat. The effect of naloxone, a narcotic antagonist, on the response of animals to painful stimuli during anesthesia was studied. Rats were anesthetized with cyclopropane, halothane, or enflurane in groups of 12. Following induction, inspired anesthetic concentration was gradually reduced to a point at which 35-60 per cent of animals responded to tail clamping. Thereafter the anesthetic concentration was held constant for 30 minutes. Rats in each group then received saline solution or naloxone, 10mg/kg, given intravenously. The response to tail clamping was retested 5 minutes later. In additional experiments EEG's were recorded from rats anesthesized with one of these anesthetics. After a stable light plane of anesthesia had been attained, each animal was given naloxone, 10 mg/kg, iv, and the EEG recorded for an additional 5 minutes. In the tail-clamping experiments, naloxone approximately doubled the number of rats responding during cyclopropane, halothane, or enflurane anesthesia. The EEG patterns of several animals anesthetized with either cyclopropane or halothane changed to patterns consistent with lighter planes of anesthesia after naloxone administration. That naloxone alters the depth of inhalational anesthesia suggests that anesthetics may release an endogenous morphine-like factor (MLF) in the central nervous system."}
{"id": "PMID:190925", "title": "Evaluation of a feline viral rhinotracheitis-feline calicivirus disease vaccine.", "content": "An attenuated respiratory disease vaccine against feline viral rhinotracheitis (FVR) and feline calicivirus (FCV) disease was evaluated for safety and efficacy in specific-pathogen-free cats. Twenty cats were vaccinated twice intramuscularly, with 28 days between vaccinations. Ten unvaccinated cats were used as contact controls. Adverse effects were not noticed after vaccination, and the vaccinal virus did not spread to contact controls. Arithmetical mean serum-neutralizing titers against vaccinal FCV strain F9 and challenge FCV strain 255 were 1:13 and 1:15 at 28 days after the 1st inoculation. These titers increased to 1:45 and 1:196 after the 2nd inoculation. After challenge exposure of vaccinated cats to virulent FCV 255 virus, mean titers increased to 1:129 and 1:865, respectively for F9 and 255 viruses. The F9 postchallenge mean titer for vaccinated cats was 21.5 times higher than that for the 8 contact controls that survived challenge exposure. The arithmetical mean serum neutralizing titer for FVR was low (1:2) after the 1st vaccination, but increased to 1:35 after the 2nd vaccination. Challenge exposure to virulent FVR virus resulted in a marked anamnestic immune response (mean titer of 1:207, compared with 1:12 for contact controls). In general, vaccinated cats remained alert and healthy after challenge exposure with FCV-255, whereas unvaccinated contact control cats developed definite signs of FCV disease, including central nervous system (CNS) depression (6 of 10) and dyspnea indicative of pneumonia (5 of 10). Two controls died of severe pneumonia. A mild fibrile response was detected in 28% of vaccinated cats, compared with a more severe febrile response in 78% of control cats. Some vaccinated cats developed minute lingual ulcers that did not appear to be detrimental to the health of the cat. After FVR challenge exposure, vaccinated cats were free of serious clinical signs. Five of 18 vaccinated cats had mild signs of FVR, including an occasional sneeze, low temperature, and mild serous lacrimation for 1 or 2 days. Contact controls developed definite clinical signs of FVR. The combined FVR-FCV vaccine appears to be safe and reasonably efficacious. Vaccination against FCV disease and FVR should be part of the routine feline immunization program.", "contents": "Evaluation of a feline viral rhinotracheitis-feline calicivirus disease vaccine. An attenuated respiratory disease vaccine against feline viral rhinotracheitis (FVR) and feline calicivirus (FCV) disease was evaluated for safety and efficacy in specific-pathogen-free cats. Twenty cats were vaccinated twice intramuscularly, with 28 days between vaccinations. Ten unvaccinated cats were used as contact controls. Adverse effects were not noticed after vaccination, and the vaccinal virus did not spread to contact controls. Arithmetical mean serum-neutralizing titers against vaccinal FCV strain F9 and challenge FCV strain 255 were 1:13 and 1:15 at 28 days after the 1st inoculation. These titers increased to 1:45 and 1:196 after the 2nd inoculation. After challenge exposure of vaccinated cats to virulent FCV 255 virus, mean titers increased to 1:129 and 1:865, respectively for F9 and 255 viruses. The F9 postchallenge mean titer for vaccinated cats was 21.5 times higher than that for the 8 contact controls that survived challenge exposure. The arithmetical mean serum neutralizing titer for FVR was low (1:2) after the 1st vaccination, but increased to 1:35 after the 2nd vaccination. Challenge exposure to virulent FVR virus resulted in a marked anamnestic immune response (mean titer of 1:207, compared with 1:12 for contact controls). In general, vaccinated cats remained alert and healthy after challenge exposure with FCV-255, whereas unvaccinated contact control cats developed definite signs of FCV disease, including central nervous system (CNS) depression (6 of 10) and dyspnea indicative of pneumonia (5 of 10). Two controls died of severe pneumonia. A mild fibrile response was detected in 28% of vaccinated cats, compared with a more severe febrile response in 78% of control cats. Some vaccinated cats developed minute lingual ulcers that did not appear to be detrimental to the health of the cat. After FVR challenge exposure, vaccinated cats were free of serious clinical signs. Five of 18 vaccinated cats had mild signs of FVR, including an occasional sneeze, low temperature, and mild serous lacrimation for 1 or 2 days. Contact controls developed definite clinical signs of FVR. The combined FVR-FCV vaccine appears to be safe and reasonably efficacious. Vaccination against FCV disease and FVR should be part of the routine feline immunization program."}
{"id": "PMID:190926", "title": "Effect of infectious bursal disease on the response of chickens to Mycoplasma synoviae, Newcastle disease virus, and infectious bronchitis virus.", "content": "At 35 days of age, chickens which as 1-day-old chicks were inoculated with the infectious bursal disease virus (IBDV) had significantly lower antibody titers against Mycoplasma synoviae, Newcastle disease virus, and infectious bronchitis virus than did those never inoculated with IBDV. The IBDV also had a marked effect on the development of air-sac lesions. Birds infected with IBDV that were later inoculated with M synoviae (day 14), Newcastle disease virus (days 14 and 28) experienced an increased incidence and greater seversity of airsacculitis than did chicks which were not exposed to IBDV.", "contents": "Effect of infectious bursal disease on the response of chickens to Mycoplasma synoviae, Newcastle disease virus, and infectious bronchitis virus. At 35 days of age, chickens which as 1-day-old chicks were inoculated with the infectious bursal disease virus (IBDV) had significantly lower antibody titers against Mycoplasma synoviae, Newcastle disease virus, and infectious bronchitis virus than did those never inoculated with IBDV. The IBDV also had a marked effect on the development of air-sac lesions. Birds infected with IBDV that were later inoculated with M synoviae (day 14), Newcastle disease virus (days 14 and 28) experienced an increased incidence and greater seversity of airsacculitis than did chicks which were not exposed to IBDV."}
{"id": "PMID:190927", "title": "Ventilatory and waking responses to CO2 in sleeping dogs.", "content": "We examined ventilatory and waking responses to hyperoxic hypercapnia in 3 dogs during natural sleep. Progressive hypercapnia was induced by a rebreathing technique, and sleep was determined by electroencephalographic and behavioral criteria. In non-rapid eye movement sleep (high-voltage, slow-frequency electroencephalography) rebreathing continued for 0.99 +/- 0.05 min (mean +/- SE) before arousal occurred, and the alveolar PCO2, at arousal was 54.2 +/- 3.4 mm Hg. In contrast, during rapid eye movement sleep, rebreathing lasted for 1.71 +/- 0.27 min (P less than 0.05) before arousal occurred and the alveolar PCO2 at arousal was 60.3 +/- 4.2 mm Hg (P less than 0.05). Linear regression analysis of breath-by-breath instantaneous minute volume of ventilation, tidal volume, and respiratory frequency against alveolar PCO2 revealed regression coefficients in rapid eye movements sleep that were 14 to 33 per cent of those found in non-rapid eye movement sleep, and correlation coefficients of 0.26 to 0.46, compared to 0.71 to 0.91 in non-rapid eye movement sleep. Thus, the link between CO2 and ventilation appeared to be strong in non-rapid eye movement sleep but considerably disrupted during rapid eye movement sleep. We conclude that centers involved in both waking and ventilatory responses to hypercapnia behave as if they are less aware of or responsive to CO2 in rapid eye movement sleep than in non-rapid eye movement sleep.", "contents": "Ventilatory and waking responses to CO2 in sleeping dogs. We examined ventilatory and waking responses to hyperoxic hypercapnia in 3 dogs during natural sleep. Progressive hypercapnia was induced by a rebreathing technique, and sleep was determined by electroencephalographic and behavioral criteria. In non-rapid eye movement sleep (high-voltage, slow-frequency electroencephalography) rebreathing continued for 0.99 +/- 0.05 min (mean +/- SE) before arousal occurred, and the alveolar PCO2, at arousal was 54.2 +/- 3.4 mm Hg. In contrast, during rapid eye movement sleep, rebreathing lasted for 1.71 +/- 0.27 min (P less than 0.05) before arousal occurred and the alveolar PCO2 at arousal was 60.3 +/- 4.2 mm Hg (P less than 0.05). Linear regression analysis of breath-by-breath instantaneous minute volume of ventilation, tidal volume, and respiratory frequency against alveolar PCO2 revealed regression coefficients in rapid eye movements sleep that were 14 to 33 per cent of those found in non-rapid eye movement sleep, and correlation coefficients of 0.26 to 0.46, compared to 0.71 to 0.91 in non-rapid eye movement sleep. Thus, the link between CO2 and ventilation appeared to be strong in non-rapid eye movement sleep but considerably disrupted during rapid eye movement sleep. We conclude that centers involved in both waking and ventilatory responses to hypercapnia behave as if they are less aware of or responsive to CO2 in rapid eye movement sleep than in non-rapid eye movement sleep."}
{"id": "PMID:190928", "title": "Studies of pulmonary and renal immunopathology after nonlethal primary sendai viral infection in normal and cyclophosphamide-treated hamsters.", "content": "Hamsters were infected by aerosol with a nonlethal strain of Sendai virus. The virus infected mainly bronchial mucosal cells, some alveolar cells, and occasional renal tubular cells. By the third day after infection, there was an impressive local influx of inflammatory and IgG-secreting cells at sites of infection, disruption and desquamation of infected mucosal cells, and destruction of bronchial basement membrane. These findings were associated with the presence of specific antibodies bound to viral antigens in the tissues. Treatment with cyclophosphamide resulted in the ablation of these histologic events, failure to eradicate virus or to produce antibody, and some spontaneous deaths. Viral antigens were regularly detected in kidneys on days 3, 6, and 9 as a fine, granular glomerular and tubular basement membrane staining pattern after elution of tissue sections. The IgG deposition was found in a similar pattern at the same times, persisted after Sendai antigens could no longer be detected, and tended toward linear staining, fading with time. Treatment with cyclophosphamide decreased significantly, but did not completely abolish, the renal abnormalities. It was concluded that the humoral immune response is associated with eradication of virus, excess local tissue damage, and some immunopathologic consequences in the kidney.", "contents": "Studies of pulmonary and renal immunopathology after nonlethal primary sendai viral infection in normal and cyclophosphamide-treated hamsters. Hamsters were infected by aerosol with a nonlethal strain of Sendai virus. The virus infected mainly bronchial mucosal cells, some alveolar cells, and occasional renal tubular cells. By the third day after infection, there was an impressive local influx of inflammatory and IgG-secreting cells at sites of infection, disruption and desquamation of infected mucosal cells, and destruction of bronchial basement membrane. These findings were associated with the presence of specific antibodies bound to viral antigens in the tissues. Treatment with cyclophosphamide resulted in the ablation of these histologic events, failure to eradicate virus or to produce antibody, and some spontaneous deaths. Viral antigens were regularly detected in kidneys on days 3, 6, and 9 as a fine, granular glomerular and tubular basement membrane staining pattern after elution of tissue sections. The IgG deposition was found in a similar pattern at the same times, persisted after Sendai antigens could no longer be detected, and tended toward linear staining, fading with time. Treatment with cyclophosphamide decreased significantly, but did not completely abolish, the renal abnormalities. It was concluded that the humoral immune response is associated with eradication of virus, excess local tissue damage, and some immunopathologic consequences in the kidney."}
{"id": "PMID:190929", "title": "The current status of chemodectomas.", "content": "An analysis of the current status of chemodectomas including the report of two additional cases is presented. One patient with a rare malignant intrathoracic tumor failed to survive palliative pneumonectomy. To our knowledge, this represents the seventeenth histologically proved case. The other patient had the more common carotid body tumor which was managed satisfactorily by subadventitial carotid excision. Comments are made regarding the clinical recognition and treatment of chemodectomas in general. Historical, anatomic, physiologic, and pathologic features are emphasized.", "contents": "The current status of chemodectomas. An analysis of the current status of chemodectomas including the report of two additional cases is presented. One patient with a rare malignant intrathoracic tumor failed to survive palliative pneumonectomy. To our knowledge, this represents the seventeenth histologically proved case. The other patient had the more common carotid body tumor which was managed satisfactorily by subadventitial carotid excision. Comments are made regarding the clinical recognition and treatment of chemodectomas in general. Historical, anatomic, physiologic, and pathologic features are emphasized."}
{"id": "PMID:190930", "title": "Epstein-Barr virus and human malignancy.", "content": "The association of the Epstein-Barr virus and two human malignancies, Burkitt's lumphoma and nasopharyngeal carcinoma, is reviewed. Seroepidemiologic, virologic, and immunologic evidence is summarized, and several hypotheses regarding a possible etiologic role for the Epstein-Barr virus in these tumors are presented. With our current state of knowledge we cannot conclude that the Ipstein-Barr virus is oncogenic in man, nor can we yet ascertain the biological and clinical significance of its association with Burkitt's lymphoma and nasopharyngeal carcinoma.", "contents": "Epstein-Barr virus and human malignancy. The association of the Epstein-Barr virus and two human malignancies, Burkitt's lumphoma and nasopharyngeal carcinoma, is reviewed. Seroepidemiologic, virologic, and immunologic evidence is summarized, and several hypotheses regarding a possible etiologic role for the Epstein-Barr virus in these tumors are presented. With our current state of knowledge we cannot conclude that the Ipstein-Barr virus is oncogenic in man, nor can we yet ascertain the biological and clinical significance of its association with Burkitt's lymphoma and nasopharyngeal carcinoma."}
{"id": "PMID:190933", "title": "[Identification of two plasmids isolated from a bacteriocinogenic strain of Clostridium perfringens].", "content": "Two plasmids were found and studied in the bacteriocinogenic strain N5 of Clostridium perfringens: one is a bacteriocinogenic factor (MW=5.7 X 10(6)) and the other a cryptic plasmid (MW 32.4 X 10(6)). Simultaneous loss of the ability to produce bacteriocin and of the bacteriocin resistance in a \"cured\" variant corresponds to the loss of the bacteriocinogenic plasmid DNA. The syntheses of haemolysin 0 and phospholipase C do not seem to be coded for by the cryptic plasmid.", "contents": "[Identification of two plasmids isolated from a bacteriocinogenic strain of Clostridium perfringens]. Two plasmids were found and studied in the bacteriocinogenic strain N5 of Clostridium perfringens: one is a bacteriocinogenic factor (MW=5.7 X 10(6)) and the other a cryptic plasmid (MW 32.4 X 10(6)). Simultaneous loss of the ability to produce bacteriocin and of the bacteriocin resistance in a \"cured\" variant corresponds to the loss of the bacteriocinogenic plasmid DNA. The syntheses of haemolysin 0 and phospholipase C do not seem to be coded for by the cryptic plasmid."}
{"id": "PMID:190938", "title": "[Dermo-neuro-hypsarrhythmia. Association of a congenital dermatosis and hypsarthymia. 9 cases (author's transl)].", "content": "These 9 cases confirm that tuberose sclerosis, von Recklinghausen's neurofibromatosis, incontinentia pigmenti, linear warty sebaceous naevus and alopecic naevus resulting in a woolly naevus of the scalp may be complicated by flexion spasms with hypsarhythmia. Early diagnosis of hypsarhythmia makes possible specific treatment with ACTH or hydrocortisone.", "contents": "[Dermo-neuro-hypsarrhythmia. Association of a congenital dermatosis and hypsarthymia. 9 cases (author's transl)]. These 9 cases confirm that tuberose sclerosis, von Recklinghausen's neurofibromatosis, incontinentia pigmenti, linear warty sebaceous naevus and alopecic naevus resulting in a woolly naevus of the scalp may be complicated by flexion spasms with hypsarhythmia. Early diagnosis of hypsarhythmia makes possible specific treatment with ACTH or hydrocortisone."}
{"id": "PMID:190939", "title": "[Some African gregarines (Ivory Coast, Gaboon) (author's transl)].", "content": "We study in the present paper two collections of Gregarines (all parasite of terrestrial arthropods) from the Ivory Coast and the Gaboon. Among the 17 species studied, three are new for science: Gregarina darchenae, Gregarina pycnoceri and Gigaductus africanus. The other species have been already found in closely related hosts.", "contents": "[Some African gregarines (Ivory Coast, Gaboon) (author's transl)]. We study in the present paper two collections of Gregarines (all parasite of terrestrial arthropods) from the Ivory Coast and the Gaboon. Among the 17 species studied, three are new for science: Gregarina darchenae, Gregarina pycnoceri and Gigaductus africanus. The other species have been already found in closely related hosts."}
{"id": "PMID:190943", "title": "[Mechanism of action of tetracycline on the functional state of the adrenal cortex].", "content": "The mechanism of stimulation of the adrenal cortex function by tetracycline was studied on albino rats. It was shown that tetracycline administered orally in a dose of 200 mg/kg regularly induced an increase in the corticosterone levels in the peripheral blood of the animals by the 15th day of the antibiotic use. It was shown on the animals with an experimentally suppressed function of the hypophysis by prolonged administration of hydrocortisone acetate that tetracycline primarily stimulated the hypophysis function resulting in production and excretion of increased amounts of the adrenocorticotropic hormone into the blood. The hormone increased the production of corticosterone in the adrenal glands which resulted in its higher levels in the peripheral blood.", "contents": "[Mechanism of action of tetracycline on the functional state of the adrenal cortex]. The mechanism of stimulation of the adrenal cortex function by tetracycline was studied on albino rats. It was shown that tetracycline administered orally in a dose of 200 mg/kg regularly induced an increase in the corticosterone levels in the peripheral blood of the animals by the 15th day of the antibiotic use. It was shown on the animals with an experimentally suppressed function of the hypophysis by prolonged administration of hydrocortisone acetate that tetracycline primarily stimulated the hypophysis function resulting in production and excretion of increased amounts of the adrenocorticotropic hormone into the blood. The hormone increased the production of corticosterone in the adrenal glands which resulted in its higher levels in the peripheral blood."}
{"id": "PMID:190944", "title": "[Effect of Actinomyces rimosus ribonuclease on the reproduction of viruses].", "content": "Antiviral activity of RNA-ase isolated from the fermentation broth of Actinomyces rimosus was studied. The effect of the enzyme on multiplication of the viruses of vesicular stomatitis, Newcastle and cariolovaccine diseases was investigated. It was found that the enzyme was capable of suppressing reproduction of the vesicular stomatitis virus (VSV) in the culture of chick fibroblast cells. The suppression level directly depended on the enzyme concentration and decreased with an increase in the infection multiplicity. The enzyme had no effect on multiplication of other viruses tested. RNA-ase decreased the infectious properties of the freshly isolated virus-containing material in concentrations showing the antiviral effect. Preliminary incubation of the cells with the enzyme resulted in suppression of the plaque formation by VSV. The RNA synthesis in such cultures treated with RNA-ase was somewhat lower. It was shown that the antiviral effect of RNA=ase was connected with its enzymic activity. RNA-ase has no antiviral effect in the experiments with mice infected with VSV.", "contents": "[Effect of Actinomyces rimosus ribonuclease on the reproduction of viruses]. Antiviral activity of RNA-ase isolated from the fermentation broth of Actinomyces rimosus was studied. The effect of the enzyme on multiplication of the viruses of vesicular stomatitis, Newcastle and cariolovaccine diseases was investigated. It was found that the enzyme was capable of suppressing reproduction of the vesicular stomatitis virus (VSV) in the culture of chick fibroblast cells. The suppression level directly depended on the enzyme concentration and decreased with an increase in the infection multiplicity. The enzyme had no effect on multiplication of other viruses tested. RNA-ase decreased the infectious properties of the freshly isolated virus-containing material in concentrations showing the antiviral effect. Preliminary incubation of the cells with the enzyme resulted in suppression of the plaque formation by VSV. The RNA synthesis in such cultures treated with RNA-ase was somewhat lower. It was shown that the antiviral effect of RNA=ase was connected with its enzymic activity. RNA-ase has no antiviral effect in the experiments with mice infected with VSV."}
{"id": "PMID:190945", "title": "[Some ways to eliminate the side effects of antibiotic therapy in experimental pneumonia].", "content": "Impairement in the process of tissue respiration at the subcellular level in growing animals with experimental pneumonia are described. Under the conditions of antibiotic therapy such impairements aggravated. A combined use of antibiotics with succinic and glutamic acids resulted in improvement of the tissue respiration and acceleration of reparation. Possible mechanisms of this phenomenon are discussed.", "contents": "[Some ways to eliminate the side effects of antibiotic therapy in experimental pneumonia]. Impairement in the process of tissue respiration at the subcellular level in growing animals with experimental pneumonia are described. Under the conditions of antibiotic therapy such impairements aggravated. A combined use of antibiotics with succinic and glutamic acids resulted in improvement of the tissue respiration and acceleration of reparation. Possible mechanisms of this phenomenon are discussed."}
{"id": "PMID:190946", "title": "[Effect of polymyxin M on intestinal microorganisms of gnotobiotic chicks].", "content": "The effect of polymyxin M on the microflora artifically introduced into the digestive tract of gnotobiotic chickens was studied. It was found that polymyxin M caused dysbacteriosis in the digestive tract. Reduction of the impaired biocenosis after discontinuation of polymyxin use was rapid and practically complete.", "contents": "[Effect of polymyxin M on intestinal microorganisms of gnotobiotic chicks]. The effect of polymyxin M on the microflora artifically introduced into the digestive tract of gnotobiotic chickens was studied. It was found that polymyxin M caused dysbacteriosis in the digestive tract. Reduction of the impaired biocenosis after discontinuation of polymyxin use was rapid and practically complete."}
{"id": "PMID:190952", "title": "Multicentric reticulohistiocytosis.", "content": "Multicentric reticulohistiocytosis is a rare disorder of the skin and joints that possesses distinctive histologic findings. A case is reported from shortly after its onset to a stage of resolution 4 1/2 years later.", "contents": "Multicentric reticulohistiocytosis. Multicentric reticulohistiocytosis is a rare disorder of the skin and joints that possesses distinctive histologic findings. A case is reported from shortly after its onset to a stage of resolution 4 1/2 years later."}
{"id": "PMID:190953", "title": "Comparative study of carcinoembryonic antigen in rheumatoid synovium, tumour, and normal adult lung.", "content": "Material reacting like carcinoembryonic antigen (CEA) in the radioimmunoassay has been extracted from rheumatoid synovial membranes. This CEA activity has been compared to that found in hepatic metastases from colorectal tumours and in normal adult lung. The antigen in the rheumatoid synovium has been shown to be more sensitive to perchloric acid and to isolate with a lower weight than that derived from the tumour and lung. Immunodiffusion studies with anti-CEA indicate that the CEA-like determinants in the rheumatoid synovium have partial identity with tumour CEA and that a significant proportion of them are associated with large molecular weight material. Production of an antiserum to these CEA-like components in the rheumatoid synovium should enable further identification of their relationship to tumour CEA and might allow a better judgement of whether or not they represent the expression of neoantigens in the disease.", "contents": "Comparative study of carcinoembryonic antigen in rheumatoid synovium, tumour, and normal adult lung. Material reacting like carcinoembryonic antigen (CEA) in the radioimmunoassay has been extracted from rheumatoid synovial membranes. This CEA activity has been compared to that found in hepatic metastases from colorectal tumours and in normal adult lung. The antigen in the rheumatoid synovium has been shown to be more sensitive to perchloric acid and to isolate with a lower weight than that derived from the tumour and lung. Immunodiffusion studies with anti-CEA indicate that the CEA-like determinants in the rheumatoid synovium have partial identity with tumour CEA and that a significant proportion of them are associated with large molecular weight material. Production of an antiserum to these CEA-like components in the rheumatoid synovium should enable further identification of their relationship to tumour CEA and might allow a better judgement of whether or not they represent the expression of neoantigens in the disease."}
{"id": "PMID:190955", "title": "Transfusion-associated cytomegalovirus mononucleosis.", "content": "Transfusion-associated cytomegalovirus mononucleosis is generally considered only as a complication of extracorporeal circulation following cardiac surgery. Three cases following trauma were recognized in less than one year. Both massive and limited volume blood transfusions were involved. Hectic fever was a characteristic feature in these otherwise remarkably asymptomatic individuals, without the classic features of heterophile-positive infectious mononucleosis. Since the illness developed several weeks into the post-operative period after extensive thoracic or abdominal trauma surgery, the presence of an undrained abscess was naturally the major diagnostic concern. Atypical lymphocytosis, markers of altered immunity (cold agglutinins, rheumatoid factor) and moderate hepatic dysfunction were important laboratory clues. In one case, focal isotope defects in the spleen scan misleadingly suggested a septic complication. A false-positive monospot test initially obscured the correct serologic diagnosis in the same patient. Failure to consider this selflimited viral infection may be a critical factor leading to unnecessary surgery. Other viral agents capable of eliciting a similar syndrome are cited.", "contents": "Transfusion-associated cytomegalovirus mononucleosis. Transfusion-associated cytomegalovirus mononucleosis is generally considered only as a complication of extracorporeal circulation following cardiac surgery. Three cases following trauma were recognized in less than one year. Both massive and limited volume blood transfusions were involved. Hectic fever was a characteristic feature in these otherwise remarkably asymptomatic individuals, without the classic features of heterophile-positive infectious mononucleosis. Since the illness developed several weeks into the post-operative period after extensive thoracic or abdominal trauma surgery, the presence of an undrained abscess was naturally the major diagnostic concern. Atypical lymphocytosis, markers of altered immunity (cold agglutinins, rheumatoid factor) and moderate hepatic dysfunction were important laboratory clues. In one case, focal isotope defects in the spleen scan misleadingly suggested a septic complication. A false-positive monospot test initially obscured the correct serologic diagnosis in the same patient. Failure to consider this selflimited viral infection may be a critical factor leading to unnecessary surgery. Other viral agents capable of eliciting a similar syndrome are cited."}
{"id": "PMID:190956", "title": "The role of right heart angiography in the management of selected cases.", "content": "Three cases of Wilms' tumor with inferior vena cava involvement are presented. All three cases were shown to have nonvisualization of the inferior vena cava on the initial intravenous pyelogram obtained by internal saphenous vein injection. The first case ended fatally, due primarily to delay in diagnosing extension of the tumor into the right atrium. There was no cardiac involvement in the other two cases, both of which were managed successfully. A right heart angiogram demonstrated intraatrial tumor in the first case and helped to identify the presence and extent of caval involvment in the other two. It is recommended that right heart angiography be performed in those cases of Wilms' tumor where the inferior vena cavagram shows non-visualization of the cava or suggests the presences of intraluminal tumor. The immediate availability of two separate surgical teams in the management of such cases is suggested.", "contents": "The role of right heart angiography in the management of selected cases. Three cases of Wilms' tumor with inferior vena cava involvement are presented. All three cases were shown to have nonvisualization of the inferior vena cava on the initial intravenous pyelogram obtained by internal saphenous vein injection. The first case ended fatally, due primarily to delay in diagnosing extension of the tumor into the right atrium. There was no cardiac involvement in the other two cases, both of which were managed successfully. A right heart angiogram demonstrated intraatrial tumor in the first case and helped to identify the presence and extent of caval involvment in the other two. It is recommended that right heart angiography be performed in those cases of Wilms' tumor where the inferior vena cavagram shows non-visualization of the cava or suggests the presences of intraluminal tumor. The immediate availability of two separate surgical teams in the management of such cases is suggested."}
{"id": "PMID:190954", "title": "[The fixing complement antibodies to respiratory viruses--influenza A1, B, C, parainfluenza 1 (Sendai), syncytial respiratory, Adenovirus, Echo 11--and \"Mycoplasma pneumoniae\" in healthy persons (author's transl)].", "content": "Serological research of complement fixation test (Kolmer micromethod) into 163 young healthy subjects (18-22 years old) in order to point out the contaminations effects of respiratory viruses and of Mycoplasma pneumoniae. In is pointed out serological simultaneous reactions on some subjects, expression of multiple infections; the different frequency of serological tests for each antigen, pointing out the r\u00f4ll played by the singles diseases, the different titre distribution of the antibodies to 1:4 to 1:128. It is pointed out the value of the antibodies patrimony in existence in healthy persons, in order to prevent the diseases caused by virus and Mycoplasma pneumoniae. It is stressed the r\u00f4ll of some mammalia and birds as hosts of human influenza virus, subjects of mutation in such organismes. The new virus attack the man with the virus pertinent to the animals, in special way to equins and birds.", "contents": "[The fixing complement antibodies to respiratory viruses--influenza A1, B, C, parainfluenza 1 (Sendai), syncytial respiratory, Adenovirus, Echo 11--and \"Mycoplasma pneumoniae\" in healthy persons (author's transl)]. Serological research of complement fixation test (Kolmer micromethod) into 163 young healthy subjects (18-22 years old) in order to point out the contaminations effects of respiratory viruses and of Mycoplasma pneumoniae. In is pointed out serological simultaneous reactions on some subjects, expression of multiple infections; the different frequency of serological tests for each antigen, pointing out the r\u00f4ll played by the singles diseases, the different titre distribution of the antibodies to 1:4 to 1:128. It is pointed out the value of the antibodies patrimony in existence in healthy persons, in order to prevent the diseases caused by virus and Mycoplasma pneumoniae. It is stressed the r\u00f4ll of some mammalia and birds as hosts of human influenza virus, subjects of mutation in such organismes. The new virus attack the man with the virus pertinent to the animals, in special way to equins and birds."}
{"id": "PMID:190957", "title": "Grand rounds: autoimmune hemolytic anemia.", "content": "Autoimmune hemolytic anemia (AHA) may be either primary (ie, \"idiopathic,\" one third of all patients) or secondary (ie, associated with underlying illness, two thirds of all patients). A positive Coombs antiglobulin test is the most important criterion for diagnosis of AHA, and characterization of RBC coating (as to whether it is by IgG alone, by IgG plus complement, or by complement alone) may be valuable in ruling out certain underlying illnesses as causative in selected patients. Many limitations to the antiglobulin test must be kept in mind. As routinely performed, a positive result requires greater than 500 molecules of IgG per RBC. Red blood cells from normal subjects have less than 35 molecules of IgG per RBC. Up to 2% to 5% of patients with AHA will have RBC coating in the 50 to 500 molecules per cell range and may therefore have \"false\"-negative antiglobulin tests. Apparent failures of strength of antiglobulin reactions to correlate with severity of in vivo RBC destruction may result from technical factors or may reflect intrinsic differences among autoantibodies (eg, IgG subclass, affinity). A likely mechanism of in vivo RBC destruction in AHA has been demonstrated in immune-mediated in vitro RBC \"rosette\" formation about macrophages and lymphocytes bearing specific receptors for subclasses of IgG and for subcomponents of complement. Increased avidity of macrophages for coated RBCs in response to such stimulus as infection may play an additional role. Treatment involves control of underlying disease and the judicious use of adrenal steroids, splenectomy, and immunosuppressive agents. Transfusions, while life-saving in life-threatening anemia, carry substantially increased risks in AHA patients. Their use should be strictly limited.", "contents": "Grand rounds: autoimmune hemolytic anemia. Autoimmune hemolytic anemia (AHA) may be either primary (ie, \"idiopathic,\" one third of all patients) or secondary (ie, associated with underlying illness, two thirds of all patients). A positive Coombs antiglobulin test is the most important criterion for diagnosis of AHA, and characterization of RBC coating (as to whether it is by IgG alone, by IgG plus complement, or by complement alone) may be valuable in ruling out certain underlying illnesses as causative in selected patients. Many limitations to the antiglobulin test must be kept in mind. As routinely performed, a positive result requires greater than 500 molecules of IgG per RBC. Red blood cells from normal subjects have less than 35 molecules of IgG per RBC. Up to 2% to 5% of patients with AHA will have RBC coating in the 50 to 500 molecules per cell range and may therefore have \"false\"-negative antiglobulin tests. Apparent failures of strength of antiglobulin reactions to correlate with severity of in vivo RBC destruction may result from technical factors or may reflect intrinsic differences among autoantibodies (eg, IgG subclass, affinity). A likely mechanism of in vivo RBC destruction in AHA has been demonstrated in immune-mediated in vitro RBC \"rosette\" formation about macrophages and lymphocytes bearing specific receptors for subclasses of IgG and for subcomponents of complement. Increased avidity of macrophages for coated RBCs in response to such stimulus as infection may play an additional role. Treatment involves control of underlying disease and the judicious use of adrenal steroids, splenectomy, and immunosuppressive agents. Transfusions, while life-saving in life-threatening anemia, carry substantially increased risks in AHA patients. Their use should be strictly limited."}
{"id": "PMID:190958", "title": "Focal nodular hyperplasia of the liver associated with high-dosage estrogens.", "content": "A patient developed benign nodular hyperplasia of the liver after long-term, high-dose estrogen therapy. A 10.5-cm benign liver nodule appeared after three years of high-dose estrogen therapy and was resected. Fourteen months later, while still receiving estrogen, a 4.5-cm nodule and multiple small nodules were seen on angiography. Four months after estrogen was discontinued, the larger liver nodule disappeared and the smaller ones decreased.", "contents": "Focal nodular hyperplasia of the liver associated with high-dosage estrogens. A patient developed benign nodular hyperplasia of the liver after long-term, high-dose estrogen therapy. A 10.5-cm benign liver nodule appeared after three years of high-dose estrogen therapy and was resected. Fourteen months later, while still receiving estrogen, a 4.5-cm nodule and multiple small nodules were seen on angiography. Four months after estrogen was discontinued, the larger liver nodule disappeared and the smaller ones decreased."}
{"id": "PMID:190959", "title": "Sulfonylurea-induced factitious hypoglycemia. A growing problem.", "content": "Two patients had sulfonylurea-induced factitious hypoglycemia. Both patients demonstrated hyperinsulinism during hypoglycemia suggesting the presence of an insulin-secreting tumor. One patient underwent an exploratory laparotomy with subtotal pancreatectomy before the etiology of the hypoglycemia was discovered. Inboth patients, the diagnosis was made by detecting sulfonylurea agents in blood. A survey of Portland, Ore metropolitan hospitals suggests that factitious hypoglycemia occurs with a frequency similar to the insulinoma syndrome. The biochemical similarity of these disorders and the apparent increasing incidence of factitious hypoglycemia suggests that blood determinations of sulfonylurea agents should be performed prior to exploratory laparotomy for an insulinoma.", "contents": "Sulfonylurea-induced factitious hypoglycemia. A growing problem. Two patients had sulfonylurea-induced factitious hypoglycemia. Both patients demonstrated hyperinsulinism during hypoglycemia suggesting the presence of an insulin-secreting tumor. One patient underwent an exploratory laparotomy with subtotal pancreatectomy before the etiology of the hypoglycemia was discovered. Inboth patients, the diagnosis was made by detecting sulfonylurea agents in blood. A survey of Portland, Ore metropolitan hospitals suggests that factitious hypoglycemia occurs with a frequency similar to the insulinoma syndrome. The biochemical similarity of these disorders and the apparent increasing incidence of factitious hypoglycemia suggests that blood determinations of sulfonylurea agents should be performed prior to exploratory laparotomy for an insulinoma."}
{"id": "PMID:190960", "title": "A mathematical model for the mechanism of rapid eye movements induced by an anticholinesterase in the decerebrate cat.", "content": "The oculomotor pattern which appears in intact preparations during desynchronized sleep is characterized by the irregular occurrence of isolated ocular movements and bursts of rapid eye movements (REM). This complex oculomotor pattern results from the activity of two premotor structures which influence the extraocular motoneurons during this phase of sleep: one is located in the pontine reticular formation, the other in the vestibular nuclei. In the decerebrate preparation the intravenous injection of an anticholinesterase leads to the appearance of a typical pattern of oculomotor activity, which differs from that occurring during physiological sleep in so far as it consists quite exclusively of bursts of REM which appear at very regular intervals. Lesion experiments as well as unit recordings have shown that these bursts of REM depend in particular upon rhythmic discharges of the vestibular nuclear neurons. The underlying anatomical structures responsible for these bursts of REM are therefore the vestibular nuclei, the oculomotor nuclei and the oculo-orbital system. This mechanism is under the influence of cholinergic reticular neurons which generate the oculomotor rhythm. We have postulated the existence of a self-excitatory cholinergic system, located in the pontine reticular formation, whose steady discharge impinges upon an oscillatory neuronal system located in the dorso-lateral pontine tegmentum, which transforms the tonic input into a sinusoidal final output. We have assumed also that the periodic increases in the discharge frequency of this oscillatory system trigger a fast phase generator acting on the different components of the REM system, and that the behavior of each component follows a first-order differential equation. The state of excitation of the components of the system is defined as proportional to frequency of nerve impulses. Assuming ipsilateral and crossed connections, a pattern of oculomotor activity is obtained that simulates the experimental oculomotor output fairly well. The repetition of the eye jerks is described by a Fourier series. The model proposed in this paper may be taken as a first approach in describing the generation mechanism of REM, and as a theoretical guide to new experimental researches and the development of other more realistic models.", "contents": "A mathematical model for the mechanism of rapid eye movements induced by an anticholinesterase in the decerebrate cat. The oculomotor pattern which appears in intact preparations during desynchronized sleep is characterized by the irregular occurrence of isolated ocular movements and bursts of rapid eye movements (REM). This complex oculomotor pattern results from the activity of two premotor structures which influence the extraocular motoneurons during this phase of sleep: one is located in the pontine reticular formation, the other in the vestibular nuclei. In the decerebrate preparation the intravenous injection of an anticholinesterase leads to the appearance of a typical pattern of oculomotor activity, which differs from that occurring during physiological sleep in so far as it consists quite exclusively of bursts of REM which appear at very regular intervals. Lesion experiments as well as unit recordings have shown that these bursts of REM depend in particular upon rhythmic discharges of the vestibular nuclear neurons. The underlying anatomical structures responsible for these bursts of REM are therefore the vestibular nuclei, the oculomotor nuclei and the oculo-orbital system. This mechanism is under the influence of cholinergic reticular neurons which generate the oculomotor rhythm. We have postulated the existence of a self-excitatory cholinergic system, located in the pontine reticular formation, whose steady discharge impinges upon an oscillatory neuronal system located in the dorso-lateral pontine tegmentum, which transforms the tonic input into a sinusoidal final output. We have assumed also that the periodic increases in the discharge frequency of this oscillatory system trigger a fast phase generator acting on the different components of the REM system, and that the behavior of each component follows a first-order differential equation. The state of excitation of the components of the system is defined as proportional to frequency of nerve impulses. Assuming ipsilateral and crossed connections, a pattern of oculomotor activity is obtained that simulates the experimental oculomotor output fairly well. The repetition of the eye jerks is described by a Fourier series. The model proposed in this paper may be taken as a first approach in describing the generation mechanism of REM, and as a theoretical guide to new experimental researches and the development of other more realistic models."}
{"id": "PMID:190961", "title": "Selective discharge of pontine neurons during the postural atonia produced by an anticholinesterase in the decerebrate cat.", "content": "I. Episodes of postural atonia associated with bursts of REM similar to those which occur spontaneously either in the intact preparation during desynchronized sleep, or in the chronic decorticate or decerebrate preparations, can be elicited in acute decerebrate cats following intravenous injection of small doses of an anticholinesterase. The present experiments were performed in precollicular decerebrate animals in order to identify the pontine neurons which show increases in their firing rate related in time with the appearance of the cataplectic episodes. In particular long-term recordings of single units were obtained before, during and after the episodes of postural atonia produced by i.v. injection of 0.03-0.1 mg/kg of eserine sulphate. Spontaneous discharge rates were used to measure the selectivity of each individual unit, i.e., the tendency of the unit to discharge more during the cataplectic episode than during the postural rigidity. The physiological data obtained from neurons histologically localized in different nuclear groups were then averaged. 2. Neurons localized in the pontine reticular formation as well as in the region of the locus coeruleus and the raphe system showed low rates of discharge when rigidity was present. The same units, however, showed a remarkable increase in firing rate which preceded by several tenths of seconds the onset of postural atonia and lasted throughout the cataplectic episodes. 3. The neurons of the pontine reticular formation had a selectivity which was higher than that of the neurons located in the locus coeruleus-raphe system; moreover the cells of the gigantocellular tegmental field (FTG) had the highest selectivity of all pontine reticular structures studied. 4. The relation of the discharge rate curves to the occurrence of the cataplectic episodes suggests that these neurons constitute output elements of a generator system for postural atonia. It is postulated that these pontine reticular neurons are directly involved in the activation of the bulbospinal inhibitory system, which is finally responsible for the abolition of the decerebrate rigidity. 5. During cataplectic episodes these pontine neurons showed some clustered discharges which appeared in association with bursts of eye movements. In most instances, however, there was no constant relationship of the unit activity to individual eye movements. Moreover large phasic increases in firing rate appeared also during the intervals between successive bursts of REM. 6. The striking increase in firing rate of the FTG neurons observed during the cataplectic episodes cannot be attributed to an increased excitatory input to these neurons. In fact excitatory influences following intense somatic stimulation are unlikely to occur during the cataplectic episodes; moreover the response of these neurons to intense somatosensory stimulations did not reach rates comparable with those occurring spontaneously during the induced cataplectic episodes...", "contents": "Selective discharge of pontine neurons during the postural atonia produced by an anticholinesterase in the decerebrate cat. I. Episodes of postural atonia associated with bursts of REM similar to those which occur spontaneously either in the intact preparation during desynchronized sleep, or in the chronic decorticate or decerebrate preparations, can be elicited in acute decerebrate cats following intravenous injection of small doses of an anticholinesterase. The present experiments were performed in precollicular decerebrate animals in order to identify the pontine neurons which show increases in their firing rate related in time with the appearance of the cataplectic episodes. In particular long-term recordings of single units were obtained before, during and after the episodes of postural atonia produced by i.v. injection of 0.03-0.1 mg/kg of eserine sulphate. Spontaneous discharge rates were used to measure the selectivity of each individual unit, i.e., the tendency of the unit to discharge more during the cataplectic episode than during the postural rigidity. The physiological data obtained from neurons histologically localized in different nuclear groups were then averaged. 2. Neurons localized in the pontine reticular formation as well as in the region of the locus coeruleus and the raphe system showed low rates of discharge when rigidity was present. The same units, however, showed a remarkable increase in firing rate which preceded by several tenths of seconds the onset of postural atonia and lasted throughout the cataplectic episodes. 3. The neurons of the pontine reticular formation had a selectivity which was higher than that of the neurons located in the locus coeruleus-raphe system; moreover the cells of the gigantocellular tegmental field (FTG) had the highest selectivity of all pontine reticular structures studied. 4. The relation of the discharge rate curves to the occurrence of the cataplectic episodes suggests that these neurons constitute output elements of a generator system for postural atonia. It is postulated that these pontine reticular neurons are directly involved in the activation of the bulbospinal inhibitory system, which is finally responsible for the abolition of the decerebrate rigidity. 5. During cataplectic episodes these pontine neurons showed some clustered discharges which appeared in association with bursts of eye movements. In most instances, however, there was no constant relationship of the unit activity to individual eye movements. Moreover large phasic increases in firing rate appeared also during the intervals between successive bursts of REM. 6. The striking increase in firing rate of the FTG neurons observed during the cataplectic episodes cannot be attributed to an increased excitatory input to these neurons. In fact excitatory influences following intense somatic stimulation are unlikely to occur during the cataplectic episodes; moreover the response of these neurons to intense somatosensory stimulations did not reach rates comparable with those occurring spontaneously during the induced cataplectic episodes..."}
{"id": "PMID:190962", "title": "The oscillatory system responsible for the oculomotor activity during the bursts of REM.", "content": "1. In precollicular decerebrate cats the electrical activity of single pontine neurons was recorded before, during and after the episodes of postural atonia produced by i.v. injection of 0.03-0.1 mg/kg of eserine sulphate. These episodes were characterized by the regular occurrence of horizontal conjugate eye movements, which were mainly grouped in bursts of REM; moreover, a burst of REM in one direction was generally followed by a burst of REM in the opposite direction. 2. Among the recorded units, 32 showed an increase in their discharge rate during these cataplectic episodes. However, while these units fired at regular frequency when postural rigidity was present, they showed periodic changes in their discharge rate as soon as the bursts of REM appeared in the electrooculogram. In particular a nearly sinusoidal increase in the discharge rate was related to the appearance of an ocular burst in one direction, while a decrease in the unit discharge occurred during an ocular burst in the opposite direction. In some instances neighbouring pontine units located within each side of the brain stem showed reciprocal rate profiles during REM bursts oriented in a given direction, making it likely that the cyclic alternation of their activity depended upon their reciprocal interaction. 3. The alternative hypothesis, i.e., that these periodic changes in unit discharge depend upon the proprioceptive feedback due to the eye movements was excluded by the fact that these changes started before the occurrence of the bursts of REM and began to decline before the end of the burst. Moreover no variation in their firing rate was observed during the positional nystagmus induced by tilting the animal in the control period, i.e., when postural rigidity had reappeared following the end of the cataplectic episode. 4. Most of the neurons showing periodic changes in their discharge frequency during the bursts of REM were located in the pontine reticular formation. Scattered units were also found within the region of the locus coeruleus and the raphe system, close to the surrounding reticular structures. 5. In addition to these neurons, 60 pontine units were recorded, which did not show any changes in their discharge rate during transition from the control period to the cataplectic episode. However, phsiic increases or phasic decreases in their discharge rate appeared synchronously with the individual eye movements. Since in most instances these phasic changes in unit activity coincided with the appearance of the individual monophasic potentials recorded from the ascending MLB, which immediately preceded the rapid eye movements, these units could be attributed either to the premotor neurons responsible for these REM or to the closely related structures which generate their rhythmic discharge. In only a few instances did the discharge of these units not precede but follow the individual eye movements, indicating that they resulted from a proprioceptive feedback originating during the eye movements. 6...", "contents": "The oscillatory system responsible for the oculomotor activity during the bursts of REM. 1. In precollicular decerebrate cats the electrical activity of single pontine neurons was recorded before, during and after the episodes of postural atonia produced by i.v. injection of 0.03-0.1 mg/kg of eserine sulphate. These episodes were characterized by the regular occurrence of horizontal conjugate eye movements, which were mainly grouped in bursts of REM; moreover, a burst of REM in one direction was generally followed by a burst of REM in the opposite direction. 2. Among the recorded units, 32 showed an increase in their discharge rate during these cataplectic episodes. However, while these units fired at regular frequency when postural rigidity was present, they showed periodic changes in their discharge rate as soon as the bursts of REM appeared in the electrooculogram. In particular a nearly sinusoidal increase in the discharge rate was related to the appearance of an ocular burst in one direction, while a decrease in the unit discharge occurred during an ocular burst in the opposite direction. In some instances neighbouring pontine units located within each side of the brain stem showed reciprocal rate profiles during REM bursts oriented in a given direction, making it likely that the cyclic alternation of their activity depended upon their reciprocal interaction. 3. The alternative hypothesis, i.e., that these periodic changes in unit discharge depend upon the proprioceptive feedback due to the eye movements was excluded by the fact that these changes started before the occurrence of the bursts of REM and began to decline before the end of the burst. Moreover no variation in their firing rate was observed during the positional nystagmus induced by tilting the animal in the control period, i.e., when postural rigidity had reappeared following the end of the cataplectic episode. 4. Most of the neurons showing periodic changes in their discharge frequency during the bursts of REM were located in the pontine reticular formation. Scattered units were also found within the region of the locus coeruleus and the raphe system, close to the surrounding reticular structures. 5. In addition to these neurons, 60 pontine units were recorded, which did not show any changes in their discharge rate during transition from the control period to the cataplectic episode. However, phsiic increases or phasic decreases in their discharge rate appeared synchronously with the individual eye movements. Since in most instances these phasic changes in unit activity coincided with the appearance of the individual monophasic potentials recorded from the ascending MLB, which immediately preceded the rapid eye movements, these units could be attributed either to the premotor neurons responsible for these REM or to the closely related structures which generate their rhythmic discharge. In only a few instances did the discharge of these units not precede but follow the individual eye movements, indicating that they resulted from a proprioceptive feedback originating during the eye movements. 6..."}
{"id": "PMID:190963", "title": "Sequential discharges of phasic activities (PGO waves) during paradoxical sleep after selective cortical lesions in the cat.", "content": "We investigated the role that cortical areas have upon the sequences of PGO waves and associated phasic activity in the lateral rectus muscles of the eyes (PALRE) during PS. We performed several combined type of lesions (bilateral ablations of frontal lobes carried out in two sessions, or occipital lesions combined with bifrontla lobotomies). We used statistical methods previously described for the normal cat (4). We showed that frontal lesions need to be bilateral in order to be effective, that thereafter there is a recovery in the complexity of the patterns in the survival period. We showed that occipital lobectomies \"per se\" do not affect the PGO pattern, but their combination with bifrontal lobotomies produce the most dramatic changes which lasted throughout the survival period. These findings are discussed on the light of the well known anatomical cortical projections to brain stem structures which participate in the determinism of PGO waves during paradoxical sleep.", "contents": "Sequential discharges of phasic activities (PGO waves) during paradoxical sleep after selective cortical lesions in the cat. We investigated the role that cortical areas have upon the sequences of PGO waves and associated phasic activity in the lateral rectus muscles of the eyes (PALRE) during PS. We performed several combined type of lesions (bilateral ablations of frontal lobes carried out in two sessions, or occipital lesions combined with bifrontla lobotomies). We used statistical methods previously described for the normal cat (4). We showed that frontal lesions need to be bilateral in order to be effective, that thereafter there is a recovery in the complexity of the patterns in the survival period. We showed that occipital lobectomies \"per se\" do not affect the PGO pattern, but their combination with bifrontal lobotomies produce the most dramatic changes which lasted throughout the survival period. These findings are discussed on the light of the well known anatomical cortical projections to brain stem structures which participate in the determinism of PGO waves during paradoxical sleep."}
{"id": "PMID:190964", "title": "Polyhedral inclusion bodies in cells of Nitrosomonas spec.", "content": "Polyhedral inclusion bodies were observed in cells of a Nitrosomonas species. They were present in growing cells as well as in resting cells. In thin sections their size was about 130 nm in growing cells and about 185 nm in diameter in resting cells. The bodies were commonly located in the nucleoplasm. They appeared to be bounded by a nonunit membrane and had a granular substructure. In thin sections about 70% of the exponentially grown cells and about 20% of the resting cells of the investigated strain showed 1-7 respectively 1-3 inclusion bodies.", "contents": "Polyhedral inclusion bodies in cells of Nitrosomonas spec. Polyhedral inclusion bodies were observed in cells of a Nitrosomonas species. They were present in growing cells as well as in resting cells. In thin sections their size was about 130 nm in growing cells and about 185 nm in diameter in resting cells. The bodies were commonly located in the nucleoplasm. They appeared to be bounded by a nonunit membrane and had a granular substructure. In thin sections about 70% of the exponentially grown cells and about 20% of the resting cells of the investigated strain showed 1-7 respectively 1-3 inclusion bodies."}
{"id": "PMID:190967", "title": "[Various physical and chemical properties of the 73s unit of the foot-and-mouth disease virus].", "content": "At all 3 studied FMD-viruses typs O2, A5 and C we could show the 73S unit in the analytical ultracentrifuge and in the electron microscope. 73S unit is found in the normal cycle of purification of virus and by density gradient centrifugation separated and purified. In CsCl pH 7.6 its density is 1.308 +/- 0,005 g/ml. Its sedimentation coefficient has a value of 72.7 +/- 1,5S. In electron microscope it show itself as a empty virus capsid. Its diameter is in partial purified preparations with 25 +/- 1 nm the same as of the virion. Its wall diameter is 2 to 3 nm. Further purification induced defiguration of particles and increase of its diameter. 73S unit dissociates in 19S and 12S units and shows a typical protein-UV-absorption spectrum with a maximum at 276 to 278 nm and a minimum at 250 nm. Emax/Emin is 2.3. Extinction coefficient E276nm is 1,4 mg/cm2. By sucrose density gradient centrifugation and titration of fractions in the complement fixation test it was detected, that croude virus solution contained already the 73S unit.", "contents": "[Various physical and chemical properties of the 73s unit of the foot-and-mouth disease virus]. At all 3 studied FMD-viruses typs O2, A5 and C we could show the 73S unit in the analytical ultracentrifuge and in the electron microscope. 73S unit is found in the normal cycle of purification of virus and by density gradient centrifugation separated and purified. In CsCl pH 7.6 its density is 1.308 +/- 0,005 g/ml. Its sedimentation coefficient has a value of 72.7 +/- 1,5S. In electron microscope it show itself as a empty virus capsid. Its diameter is in partial purified preparations with 25 +/- 1 nm the same as of the virion. Its wall diameter is 2 to 3 nm. Further purification induced defiguration of particles and increase of its diameter. 73S unit dissociates in 19S and 12S units and shows a typical protein-UV-absorption spectrum with a maximum at 276 to 278 nm and a minimum at 250 nm. Emax/Emin is 2.3. Extinction coefficient E276nm is 1,4 mg/cm2. By sucrose density gradient centrifugation and titration of fractions in the complement fixation test it was detected, that croude virus solution contained already the 73S unit."}
{"id": "PMID:190968", "title": "[Experimental reproduction of necrotic enteritis in the chicken. 1. Mono- and polyinfections with Clostridium perfringens and coccidia with reference to cage managemen].", "content": "Experimental mono-infection and poly-infection, using vegetative germs of a CL. perfringens Type A strain 1663 and its toxin as well as E. acervulina, necatrix or mitis oocysts, were applied to 100 SPF chicken aged seven days. While clostridial or coccidial mono-infection did not cause any loss and only unspecific pathologic-anatomic changes, polyinfection was accompanied by diarrhoea and slower weight increase, with 55.4 per cent of the chicken having been lost three to nine days from the outbreak of the infection. The pathologic-anatomic findings recorded from the chicken with poly-infections included haemorrhagic, ulcerative, and necrotic intestinal inflammations, primarily in the small intestin. The results of these experimental infections indicated a possible correlation between CL. perfringens and coccidia in the pathogenesis of necrotic enteritis.", "contents": "[Experimental reproduction of necrotic enteritis in the chicken. 1. Mono- and polyinfections with Clostridium perfringens and coccidia with reference to cage managemen]. Experimental mono-infection and poly-infection, using vegetative germs of a CL. perfringens Type A strain 1663 and its toxin as well as E. acervulina, necatrix or mitis oocysts, were applied to 100 SPF chicken aged seven days. While clostridial or coccidial mono-infection did not cause any loss and only unspecific pathologic-anatomic changes, polyinfection was accompanied by diarrhoea and slower weight increase, with 55.4 per cent of the chicken having been lost three to nine days from the outbreak of the infection. The pathologic-anatomic findings recorded from the chicken with poly-infections included haemorrhagic, ulcerative, and necrotic intestinal inflammations, primarily in the small intestin. The results of these experimental infections indicated a possible correlation between CL. perfringens and coccidia in the pathogenesis of necrotic enteritis."}
{"id": "PMID:190969", "title": "[Experimental reproduction of necrotic enteritis in the chicken. 2. Further mono- and polyinfections with CL. perfringens and coccidia with special reference to ground-kept chickens].", "content": "Coccidial oocysts and/or vegetative germs, spores, and toxins of Cl. perfringens Type A were used in mono-infection and poly-infection experiments on SPF chicken aged seven and 56 days and kept under different conditions. Necrotic enteritis was regularly reproduced in all experimental groups with polyinfections. In chicken aged seven days necrotic enteritis was reproduced even after repeated mono-infections with 4 X 10(9) gerus and toxin of Cl. perfringens. The loss figures recorded from ground-kept infected groups were higher than those established from the cage-kept animals. The pathologica-anatomic findings recorded from the dead chicken included necrotic, ulcerative, and catarrhal to haemorrhagic intestinal inflammations, with necrotic enteritis being most strongly pronounced in the ileum and jejunum. All infected groups lost not only animals but weight as well. Their average weight on the 21 st day from the onset of infection was up to 26.4 per cent lower than that of the control groups.", "contents": "[Experimental reproduction of necrotic enteritis in the chicken. 2. Further mono- and polyinfections with CL. perfringens and coccidia with special reference to ground-kept chickens]. Coccidial oocysts and/or vegetative germs, spores, and toxins of Cl. perfringens Type A were used in mono-infection and poly-infection experiments on SPF chicken aged seven and 56 days and kept under different conditions. Necrotic enteritis was regularly reproduced in all experimental groups with polyinfections. In chicken aged seven days necrotic enteritis was reproduced even after repeated mono-infections with 4 X 10(9) gerus and toxin of Cl. perfringens. The loss figures recorded from ground-kept infected groups were higher than those established from the cage-kept animals. The pathologica-anatomic findings recorded from the dead chicken included necrotic, ulcerative, and catarrhal to haemorrhagic intestinal inflammations, with necrotic enteritis being most strongly pronounced in the ileum and jejunum. All infected groups lost not only animals but weight as well. Their average weight on the 21 st day from the onset of infection was up to 26.4 per cent lower than that of the control groups."}
{"id": "PMID:190970", "title": "Temporal effects of drug and placebo in delaying relapse in schizophrenic outpatients.", "content": "The potential for unwanted side effects, particularly tardive dyskinesia, following long-term after care maintenance with antipsychotic medication has led to serious questioning of its continued use for schizophrenic patients. Does the risk of relapse decline with the passage of time? If so, is the advantage of drug therapy sustained and large enough to justify continued treatment beyond one or two years? More appropriate methods for analyzing the after care experience of 374 schizophrenic patients treated with drug or placebo reveals that while the risk of relapse does decline substantially, it remains twice as high for placebo-treated patients than drug-treated patients even after two years of treatment. The prophylactic effect of maintenance chemotherapy appears to be one to two times larger than generally estimated by the less precise \"cumulative percentage\" method.", "contents": "Temporal effects of drug and placebo in delaying relapse in schizophrenic outpatients. The potential for unwanted side effects, particularly tardive dyskinesia, following long-term after care maintenance with antipsychotic medication has led to serious questioning of its continued use for schizophrenic patients. Does the risk of relapse decline with the passage of time? If so, is the advantage of drug therapy sustained and large enough to justify continued treatment beyond one or two years? More appropriate methods for analyzing the after care experience of 374 schizophrenic patients treated with drug or placebo reveals that while the risk of relapse does decline substantially, it remains twice as high for placebo-treated patients than drug-treated patients even after two years of treatment. The prophylactic effect of maintenance chemotherapy appears to be one to two times larger than generally estimated by the less precise \"cumulative percentage\" method."}
{"id": "PMID:190971", "title": "Short vs long hospitalization: a prospective controlled study. VI Two-year follow-up results for schizophrenics.", "content": "A controlled, prospective study examined the relative effectiveness of short-term versus long-term psychiatric hospitalization. The results of a two-year follow-up of a sample of 141 schizophrenic patients are reported here. The differences favoring long-term subjects that were apparent at one year postadmission had decreased by two years postadmission. However, there appears to be an interaction between prehospital functioning and length of hospital stay, with subjects who had good prehospital functioning doing better at two years when assigned to long-term hospitalization. Subjects with poor prehospital functioning did about equally well, regardless of length of stay, and may even have showed some tendency to do better with a shorter hospital stay. This reversal of effect was more prominent for women, although this sex difference was not statistically significant.", "contents": "Short vs long hospitalization: a prospective controlled study. VI Two-year follow-up results for schizophrenics. A controlled, prospective study examined the relative effectiveness of short-term versus long-term psychiatric hospitalization. The results of a two-year follow-up of a sample of 141 schizophrenic patients are reported here. The differences favoring long-term subjects that were apparent at one year postadmission had decreased by two years postadmission. However, there appears to be an interaction between prehospital functioning and length of hospital stay, with subjects who had good prehospital functioning doing better at two years when assigned to long-term hospitalization. Subjects with poor prehospital functioning did about equally well, regardless of length of stay, and may even have showed some tendency to do better with a shorter hospital stay. This reversal of effect was more prominent for women, although this sex difference was not statistically significant."}
{"id": "PMID:190972", "title": "[The vehaviour of monoaminooxydase (MAO) activity in tumours. I. MAO activity measurement in experimental tumours (author's transl)].", "content": "The activity of MAO (EC 1.4.3.4) was measured in liver homogenates of mice with experimental tumours Sarcoma S-180 and Leukemia L-1210. The enzyme activity was determined by two methods: spectrophotometric--with benzylamine as a substrate and the second with the application of oxygen electrode and adrenaline as a substrate. An increase of the enzyme activity was observed in liver homogenates of mice with Sarcoma S-180 as compared with the controls. High activity of MAO with both substrates was also observed in Sarcoma ascites. In Leukemia L-1210 changes of activity in relation to adrenaline as a substrate were very small, but towards benzylamine the affinity of enzyme was higher (the increase of activity was about 50%).", "contents": "[The vehaviour of monoaminooxydase (MAO) activity in tumours. I. MAO activity measurement in experimental tumours (author's transl)]. The activity of MAO (EC 1.4.3.4) was measured in liver homogenates of mice with experimental tumours Sarcoma S-180 and Leukemia L-1210. The enzyme activity was determined by two methods: spectrophotometric--with benzylamine as a substrate and the second with the application of oxygen electrode and adrenaline as a substrate. An increase of the enzyme activity was observed in liver homogenates of mice with Sarcoma S-180 as compared with the controls. High activity of MAO with both substrates was also observed in Sarcoma ascites. In Leukemia L-1210 changes of activity in relation to adrenaline as a substrate were very small, but towards benzylamine the affinity of enzyme was higher (the increase of activity was about 50%)."}
{"id": "PMID:190973", "title": "Liver tumors induced by 4-dimethylaminoazobenzene: experimental basis for a chemical carcinogenesis concept.", "content": "In animals fed 4-dimethylaminoazobenzene there are modifications in the distribution of extra- and intracellular cations in liver. The correlation between the cell ionic permeability changes and the induction of cholangiocarcinoma or hepatoma is analyzed at the light of the histological and biochemical findings. A new concept of chemical carcinogenesis is stated in which the increase of passive Ca2+-influx produces mitochondria damage associated with permanent modifications of the structural and functional characteristics of the cell membranes as well as of the genetic mechanisms controlling cell division.", "contents": "Liver tumors induced by 4-dimethylaminoazobenzene: experimental basis for a chemical carcinogenesis concept. In animals fed 4-dimethylaminoazobenzene there are modifications in the distribution of extra- and intracellular cations in liver. The correlation between the cell ionic permeability changes and the induction of cholangiocarcinoma or hepatoma is analyzed at the light of the histological and biochemical findings. A new concept of chemical carcinogenesis is stated in which the increase of passive Ca2+-influx produces mitochondria damage associated with permanent modifications of the structural and functional characteristics of the cell membranes as well as of the genetic mechanisms controlling cell division."}
{"id": "PMID:190974", "title": "[Tumorigenicity of TTT dissolved in DMSO (author's transl)].", "content": "In short-term experiments TTT (trinitroso-trimethylene-triamine) dissolved in DMSO (dimethylsulfoxide) caused, when orally or intraperitoneally applied, a significant enhancement of the mitotic rate in the adrenal cortex. By long-term studies the carcinogenic action of TTT in DMSO was demonstrated. In female Wistar rats a 100% liver tumor yield was observed following chronic application. After 362 days of treatment cholangiomas had developed, hepatomas and liver carcinomas occurred after 470 days of administration of TTT dissolved in DMSO.", "contents": "[Tumorigenicity of TTT dissolved in DMSO (author's transl)]. In short-term experiments TTT (trinitroso-trimethylene-triamine) dissolved in DMSO (dimethylsulfoxide) caused, when orally or intraperitoneally applied, a significant enhancement of the mitotic rate in the adrenal cortex. By long-term studies the carcinogenic action of TTT in DMSO was demonstrated. In female Wistar rats a 100% liver tumor yield was observed following chronic application. After 362 days of treatment cholangiomas had developed, hepatomas and liver carcinomas occurred after 470 days of administration of TTT dissolved in DMSO."}
{"id": "PMID:190975", "title": "Cytomegalovirus endolabyrinthitis.", "content": "A premature male infant, who died 22 days after birth with hyaline membrane disease, was found to have had cytomegalic inclusion disease at autopsy. Histopathologic examination of the temporal bones showed cytomegalovirus (CMV) infection of the entire endolabyrinth without involvement of the neural and sensory structures. These findings support the thesis that late gestational or perinatal fetal CMV infection results in an endolymphatic labyrinthitis. We hypothesize that blood-borne virus passes from the stria vascularis into the endolymphatic spaces and infects the nonneurosensory epithelium. This pattern of infection differs from the perilabyrinthitis of human varicellazoster and experimentally produced mouse CMV.", "contents": "Cytomegalovirus endolabyrinthitis. A premature male infant, who died 22 days after birth with hyaline membrane disease, was found to have had cytomegalic inclusion disease at autopsy. Histopathologic examination of the temporal bones showed cytomegalovirus (CMV) infection of the entire endolabyrinth without involvement of the neural and sensory structures. These findings support the thesis that late gestational or perinatal fetal CMV infection results in an endolymphatic labyrinthitis. We hypothesize that blood-borne virus passes from the stria vascularis into the endolymphatic spaces and infects the nonneurosensory epithelium. This pattern of infection differs from the perilabyrinthitis of human varicellazoster and experimentally produced mouse CMV."}
{"id": "PMID:190977", "title": "Selective deprivation of sleep in pycnoleptic children. Effects of deprivation of slow-wave and REM sleep on the frequency and duration of petit mal attacks.", "content": "1. Selective deprivation of slow-wave and paradoxical sleep was performed in 10 children with pycnoleptic attacks (8 of them before anticonvulsive treatment, 2 of them while under medication). The frequency and duration of petit mal attacks were intraindividually compared during night sleep and after waking for a 5-h period. 2. After deprivation of slow-wave sleep with reduction of EEG stages 3 and 4 to about one-third of the baseline but normal duration of sleep, petit mal attacks are more frequent and long-lasting than after normal sleep or selective deprivation of REM sleep. 3. Although total sleep time is significantly diminished after selective deprivation of paradoxical sleep the frequency of attacks during the waking state was lower than after normal sleep and deprivation of slow wave sleep. This observation shows a clear i nfluence of the quality of sleep on the frequency of epileptic attacks. 4. During sleep petit mal seizures were mainly found during stages 2 and paradoxical sleep. Single spike and irregular spike were discharges, however, occurred more frequently during slow-wave sleep. Their frequency was not significantly different in the deprivation conditions. 5. In contrast to experimental data in animals, REM deprivation is less provoking to epileptic attacks outside sleep than deprivation of stages 3 and 4 sleep. Therefore a sufficient amount of slow-wave should be preserved for pycnoleptic children.", "contents": "Selective deprivation of sleep in pycnoleptic children. Effects of deprivation of slow-wave and REM sleep on the frequency and duration of petit mal attacks. 1. Selective deprivation of slow-wave and paradoxical sleep was performed in 10 children with pycnoleptic attacks (8 of them before anticonvulsive treatment, 2 of them while under medication). The frequency and duration of petit mal attacks were intraindividually compared during night sleep and after waking for a 5-h period. 2. After deprivation of slow-wave sleep with reduction of EEG stages 3 and 4 to about one-third of the baseline but normal duration of sleep, petit mal attacks are more frequent and long-lasting than after normal sleep or selective deprivation of REM sleep. 3. Although total sleep time is significantly diminished after selective deprivation of paradoxical sleep the frequency of attacks during the waking state was lower than after normal sleep and deprivation of slow wave sleep. This observation shows a clear i nfluence of the quality of sleep on the frequency of epileptic attacks. 4. During sleep petit mal seizures were mainly found during stages 2 and paradoxical sleep. Single spike and irregular spike were discharges, however, occurred more frequently during slow-wave sleep. Their frequency was not significantly different in the deprivation conditions. 5. In contrast to experimental data in animals, REM deprivation is less provoking to epileptic attacks outside sleep than deprivation of stages 3 and 4 sleep. Therefore a sufficient amount of slow-wave should be preserved for pycnoleptic children."}
{"id": "PMID:190978", "title": "The value of healing by secondary intention for sizeable defects of the face.", "content": "Sizeable facial wounds from trauma or tumor excision were allowed to heal by secondary intention in 20 patients. Because of its many advantages, including simplicity and satisfactory outcome as well as absence of donor site scarring, this most ancient mode of wound repair may be the procedure of choice under certain circumstances. The surgeon should not always feel compelled to use a flap or graft on the face when simple closure is not possible and when \"nature\" is available.", "contents": "The value of healing by secondary intention for sizeable defects of the face. Sizeable facial wounds from trauma or tumor excision were allowed to heal by secondary intention in 20 patients. Because of its many advantages, including simplicity and satisfactory outcome as well as absence of donor site scarring, this most ancient mode of wound repair may be the procedure of choice under certain circumstances. The surgeon should not always feel compelled to use a flap or graft on the face when simple closure is not possible and when \"nature\" is available."}
{"id": "PMID:190979", "title": "Paraganglioma simulating primary rib tumor.", "content": "We report an unusual case of a nonchromaffin paraganglioma, 7 cm in diameter, presenting clinically within the thorax of a 7-year-old girl as a primary rib tumor. It is believed to be the first report of such a location for this tumor. The rib of origin and parts of the two adjacent ones were removed, along with the involved middle lobe of the lung. The possibility is proposed that the ganglion cells of origin were carried to the tumor site during development of the intercostal nerve. The defect in the patient's chest wall was repaired with Marlex mesh and there is no evidence of difficulty, nor of recurrence, four and one-half years later.", "contents": "Paraganglioma simulating primary rib tumor. We report an unusual case of a nonchromaffin paraganglioma, 7 cm in diameter, presenting clinically within the thorax of a 7-year-old girl as a primary rib tumor. It is believed to be the first report of such a location for this tumor. The rib of origin and parts of the two adjacent ones were removed, along with the involved middle lobe of the lung. The possibility is proposed that the ganglion cells of origin were carried to the tumor site during development of the intercostal nerve. The defect in the patient's chest wall was repaired with Marlex mesh and there is no evidence of difficulty, nor of recurrence, four and one-half years later."}
{"id": "PMID:190980", "title": "[Ultrastructural changes in the central nervous system of monkeys in poliomyelitis].", "content": "The ultrastructure of cells of the central nervous system of Rhesus monkeys in experimental poliomyelitis caused by virus of poliomyelitis Type 3 was studied. It was found out that the virus of poliomyelitis was localized in nerve cells, astocytes, oligodendrocytes, the endothelium of capillaries and macrophages. This justifies the conclusion that pathological changes in the cells referred to the above result from reproduction of the virus therein. Ultrastructural changes in infected cells are divided into three stages: the first stage corresponded to eclipse-phase of infection; the second -- to the period of reproduction of the virus and composition of viral particles; and the third -- to the period following the escape of the virus from the cell. A definite combination of nonspecific changes in organoids of various cells with specific viral inclusions makes the ultrastructural picture of cells in poliomyelitis sufficiently characteristic for differential diagnosis. Pathogenesis of the developing lesions is discussed.", "contents": "[Ultrastructural changes in the central nervous system of monkeys in poliomyelitis]. The ultrastructure of cells of the central nervous system of Rhesus monkeys in experimental poliomyelitis caused by virus of poliomyelitis Type 3 was studied. It was found out that the virus of poliomyelitis was localized in nerve cells, astocytes, oligodendrocytes, the endothelium of capillaries and macrophages. This justifies the conclusion that pathological changes in the cells referred to the above result from reproduction of the virus therein. Ultrastructural changes in infected cells are divided into three stages: the first stage corresponded to eclipse-phase of infection; the second -- to the period of reproduction of the virus and composition of viral particles; and the third -- to the period following the escape of the virus from the cell. A definite combination of nonspecific changes in organoids of various cells with specific viral inclusions makes the ultrastructural picture of cells in poliomyelitis sufficiently characteristic for differential diagnosis. Pathogenesis of the developing lesions is discussed."}
{"id": "PMID:190981", "title": "[Cytospectrophotometric study of DNA content in dysplasia and breast cancer].", "content": "In displasia nuclei of the epithelial cells have diploid and in some cases also tetraploid set of chromosomes, the modal class of cells--paradiploid. In cancer there were noted poly- and heteroploidy changes in the modal class, which formed most often paratetraploid cells and more seldom--paraoctoploid ones. Comparison of intraductus cancer with invasive forms of carcinoma showed a displacement of the peak on the histogram towards greater and intermediate (within 4n and 8n) values of DNA, which was apparently associated with an increase in the number of aneuploid cells of the modal class as the tumour progressed. The average content of DNA in dysplasia was about 3n. In all forms of cancer it was significantly above (greater than 4n). Such average content of DNA and increase in the standard deviation (above 1.5) which reflects the degree of heteroplody, surve as objective indices of the onset of malignization.", "contents": "[Cytospectrophotometric study of DNA content in dysplasia and breast cancer]. In displasia nuclei of the epithelial cells have diploid and in some cases also tetraploid set of chromosomes, the modal class of cells--paradiploid. In cancer there were noted poly- and heteroploidy changes in the modal class, which formed most often paratetraploid cells and more seldom--paraoctoploid ones. Comparison of intraductus cancer with invasive forms of carcinoma showed a displacement of the peak on the histogram towards greater and intermediate (within 4n and 8n) values of DNA, which was apparently associated with an increase in the number of aneuploid cells of the modal class as the tumour progressed. The average content of DNA in dysplasia was about 3n. In all forms of cancer it was significantly above (greater than 4n). Such average content of DNA and increase in the standard deviation (above 1.5) which reflects the degree of heteroplody, surve as objective indices of the onset of malignization."}
{"id": "PMID:190982", "title": "[Problems of histogenesis and classification of nephroblastoma (Wilms' tumor) in children].", "content": "Nephroblastoma, a tumour of the kidney, is most often observed in children; it always includes the nephrogenous tissue in any variant of its differentiation. Histogenesis of this neoplasm is multiform and complex. Its development from very immature pluripotential (polypotent) cells (possibly, at the level of blastodermic vesicle) is not ruled out. The histological classification of nephroblastomas, offered by the author, is based on the principles of differentiation of the tumour tissue and on its histogenesis and opens new perspectives for further investigation of neoplasms and for clinico-anatomic collations.", "contents": "[Problems of histogenesis and classification of nephroblastoma (Wilms' tumor) in children]. Nephroblastoma, a tumour of the kidney, is most often observed in children; it always includes the nephrogenous tissue in any variant of its differentiation. Histogenesis of this neoplasm is multiform and complex. Its development from very immature pluripotential (polypotent) cells (possibly, at the level of blastodermic vesicle) is not ruled out. The histological classification of nephroblastomas, offered by the author, is based on the principles of differentiation of the tumour tissue and on its histogenesis and opens new perspectives for further investigation of neoplasms and for clinico-anatomic collations."}
{"id": "PMID:190983", "title": "[Ultrastructural changes in the liver in experimental hypothyroidism].", "content": "Electron microscopic studies of the liver of thyroidectomized rabbits were carried out. Ultrastructural changes in hepatocytes at various periods after the operation were established. Morphological changes in hepatic cells occurred already at early stages of hypothyrosis (1 month) and led to considerable dystrophyc processes at later stages of the experiment. In the hepatic tissue there was noted a marked myxedema, as well as a considerable intracellular edema which led to destruction of hepatocytes. The studies conducted revealed lesion of the morphological structure of the liver, impairment of general metabolic processes and of the hepatic function.", "contents": "[Ultrastructural changes in the liver in experimental hypothyroidism]. Electron microscopic studies of the liver of thyroidectomized rabbits were carried out. Ultrastructural changes in hepatocytes at various periods after the operation were established. Morphological changes in hepatic cells occurred already at early stages of hypothyrosis (1 month) and led to considerable dystrophyc processes at later stages of the experiment. In the hepatic tissue there was noted a marked myxedema, as well as a considerable intracellular edema which led to destruction of hepatocytes. The studies conducted revealed lesion of the morphological structure of the liver, impairment of general metabolic processes and of the hepatic function."}
{"id": "PMID:190984", "title": "[So-called pseudolymphomatosis of the stomach].", "content": "An observation of a polymorphnocellular variant of pseudolymphomatosis of the stomach diagnosed retrospectively is described. Initially, the case was treated as lymphogranulomatosis of the stomach, and in connection with the latter the patient was given long-term immunodepressive therapy. At autopsy (6 years later) atrophy of the lymphoreticular tissue and mucinous carcinoma of the stomach were revealed. The authors hold that the second tumour developed against the background of the immuno-depressive therapy, whereas at the beginning the condition was pseudolymphomatosis.", "contents": "[So-called pseudolymphomatosis of the stomach]. An observation of a polymorphnocellular variant of pseudolymphomatosis of the stomach diagnosed retrospectively is described. Initially, the case was treated as lymphogranulomatosis of the stomach, and in connection with the latter the patient was given long-term immunodepressive therapy. At autopsy (6 years later) atrophy of the lymphoreticular tissue and mucinous carcinoma of the stomach were revealed. The authors hold that the second tumour developed against the background of the immuno-depressive therapy, whereas at the beginning the condition was pseudolymphomatosis."}
{"id": "PMID:190986", "title": "Meningoencephalopathy secondary to infectious mononucleosis. Unusual presentation with stupor and chorea.", "content": "We report a case of infectious mononucleosis in which central nervous system involvement was the presenting and sole manifestation of the disorder. The major symptomatology consisted of stupor, chorea, and signs of aseptic meningitis. We also discuss the clinical and laboratory features of the neurological manifestations of infectious mononucleosis and the theories as to its pathogenesis.", "contents": "Meningoencephalopathy secondary to infectious mononucleosis. Unusual presentation with stupor and chorea. We report a case of infectious mononucleosis in which central nervous system involvement was the presenting and sole manifestation of the disorder. The major symptomatology consisted of stupor, chorea, and signs of aseptic meningitis. We also discuss the clinical and laboratory features of the neurological manifestations of infectious mononucleosis and the theories as to its pathogenesis."}
{"id": "PMID:190987", "title": "Reversible subacute peripheral neuropathy induced by phenytoin.", "content": "Dysesthesia and sensory and reflex loss in the legs developed in a patient treated for seizures with phenytoin (diphenylhydantoin) for one year. Her serum drug levels had been in the therapeutic range, and no other clinical toxic reactions had been noted. The peripheral neuropathy resolved when phenytoin therapy was discontinued.", "contents": "Reversible subacute peripheral neuropathy induced by phenytoin. Dysesthesia and sensory and reflex loss in the legs developed in a patient treated for seizures with phenytoin (diphenylhydantoin) for one year. Her serum drug levels had been in the therapeutic range, and no other clinical toxic reactions had been noted. The peripheral neuropathy resolved when phenytoin therapy was discontinued."}
{"id": "PMID:190989", "title": "Polypeptides from serum low-density lipoproteins of pigs (Sus domesticus).", "content": "Low-density lipoproteins floating between densities 1-006 and 1-063 g cm-3 were isolated by centrifugation of blood serum obtained from 24-h fasted pigs  (Sus domesticus). This lipoprotein fraction contained two components with Sf 1-063 values of 3-4 and 2-3 at 20 degrees C when examined by analytical ultracentrifugation. Delipidation of the lipoprotein yielded 15% recovery of soluble protein. Chromatography on Sephadex G100 in 8 M urea of these delipidation products yielded three fractions of different sizes which were present in both native and succinylated apoproteins. These fractions from the succinylated apolipoproteins were further characterized. A polypeptide fraction comprising 70% of the total protein had an apparent molecular weight of 34000 and contained greater amounts of amino acids with hydrophobic side chains than did the second fraction of apparent molecular weight 22000 which contained 15% of the protein. The third fraction of apparent molecular weight 12500 contained 15% of the protein.", "contents": "Polypeptides from serum low-density lipoproteins of pigs (Sus domesticus). Low-density lipoproteins floating between densities 1-006 and 1-063 g cm-3 were isolated by centrifugation of blood serum obtained from 24-h fasted pigs  (Sus domesticus). This lipoprotein fraction contained two components with Sf 1-063 values of 3-4 and 2-3 at 20 degrees C when examined by analytical ultracentrifugation. Delipidation of the lipoprotein yielded 15% recovery of soluble protein. Chromatography on Sephadex G100 in 8 M urea of these delipidation products yielded three fractions of different sizes which were present in both native and succinylated apoproteins. These fractions from the succinylated apolipoproteins were further characterized. A polypeptide fraction comprising 70% of the total protein had an apparent molecular weight of 34000 and contained greater amounts of amino acids with hydrophobic side chains than did the second fraction of apparent molecular weight 22000 which contained 15% of the protein. The third fraction of apparent molecular weight 12500 contained 15% of the protein."}
{"id": "PMID:190990", "title": "Comparison of collagenase activity in eosinophil and neutrophil fractions from rat peritoneal exudates.", "content": "The collagenase activity had been compared in extracts of eosinophils and of neutrophilss from peritoneal exudates in two groups of rats, one of which had been treated to augment the numbers of eosinophils and the other the numbers of neutrophils. The proportion of granulocytes to other cells in each preparation was increased by differential centrifugation over a continuous gradient. Collagenase was extracted from the fractions in which granulocytes were concentrated and the activity assayed by the radioactive fibril method. There was at least as much collagenase in the eosinophil-enriched extracts as in the neutrophil-enriched extracts. It is postulated that eosinophil collagenase may have a function in the remodelling of newly-synthesised collagen during the post-inflammatory phase of healing, since eosinophil leucocytes appear in significant numbers within the connective tissue during this phase. This suggests a different role for eosinophil collagenase than that for neutrophil collagenase, since neutrophil are present only in the early stages of inflammation, when collagen is being degraded.", "contents": "Comparison of collagenase activity in eosinophil and neutrophil fractions from rat peritoneal exudates. The collagenase activity had been compared in extracts of eosinophils and of neutrophilss from peritoneal exudates in two groups of rats, one of which had been treated to augment the numbers of eosinophils and the other the numbers of neutrophils. The proportion of granulocytes to other cells in each preparation was increased by differential centrifugation over a continuous gradient. Collagenase was extracted from the fractions in which granulocytes were concentrated and the activity assayed by the radioactive fibril method. There was at least as much collagenase in the eosinophil-enriched extracts as in the neutrophil-enriched extracts. It is postulated that eosinophil collagenase may have a function in the remodelling of newly-synthesised collagen during the post-inflammatory phase of healing, since eosinophil leucocytes appear in significant numbers within the connective tissue during this phase. This suggests a different role for eosinophil collagenase than that for neutrophil collagenase, since neutrophil are present only in the early stages of inflammation, when collagen is being degraded."}
{"id": "PMID:190991", "title": "Avian adenoviruses isolated from poultry in Queensland.", "content": "Adenoviruses isolated from Queensland poultry flocks with respiratory disease and/or egg production problems have been serotyped by comparison with Japanese and Irish types. Two serological types were recognized among 14 isolates examined; 4 were type 112 (Celo type) and the remaining 10 type 506. Isolates B1363 and B4015 were further characterized by immunodiffusion. Both isolates were shown to contain the avian adenovirus group antigen and B1363 also shared a second (type) antigen with Celo (Phelps) strain. Immuno-electron microscopy revealed the presence of adenovirus group antigen and freedom from contamination with other viruses.", "contents": "Avian adenoviruses isolated from poultry in Queensland. Adenoviruses isolated from Queensland poultry flocks with respiratory disease and/or egg production problems have been serotyped by comparison with Japanese and Irish types. Two serological types were recognized among 14 isolates examined; 4 were type 112 (Celo type) and the remaining 10 type 506. Isolates B1363 and B4015 were further characterized by immunodiffusion. Both isolates were shown to contain the avian adenovirus group antigen and B1363 also shared a second (type) antigen with Celo (Phelps) strain. Immuno-electron microscopy revealed the presence of adenovirus group antigen and freedom from contamination with other viruses."}
{"id": "PMID:190992", "title": "A mixed tumour and an adenoma both of ceruminous gland origin in a dog.", "content": "Ceruminous gland tumours are uncommon in the dog and this paper reports a case of two such tumours which arose in either ear of a 12 year old male long-haired Dachshund. Histologically, one tumour was a ceruminous adenoma and the other a rare ceruminous mixed tumour of borderline malignancy.", "contents": "A mixed tumour and an adenoma both of ceruminous gland origin in a dog. Ceruminous gland tumours are uncommon in the dog and this paper reports a case of two such tumours which arose in either ear of a 12 year old male long-haired Dachshund. Histologically, one tumour was a ceruminous adenoma and the other a rare ceruminous mixed tumour of borderline malignancy."}
{"id": "PMID:190998", "title": "The causal role of hypoalbuminemia in human nephrotic hyperlipidemia.", "content": "Serum lipids and their lipoprotein fractions were measured in 16 nephrotic syndrome patients. All component of lipids and beta-lipoprotein fractions (LDL) showed an increase in all uncomplicated patients. The increase in serum lipids were inversely proportional to the albumen level in these patients. In 3 patients, lipids and beta-lipoprotein fractions returned to near normal after treatment, the proteinuria diminished and serum albumen became normal. Most of these patients did not need any treatment for hyperlipidemia.", "contents": "The causal role of hypoalbuminemia in human nephrotic hyperlipidemia. Serum lipids and their lipoprotein fractions were measured in 16 nephrotic syndrome patients. All component of lipids and beta-lipoprotein fractions (LDL) showed an increase in all uncomplicated patients. The increase in serum lipids were inversely proportional to the albumen level in these patients. In 3 patients, lipids and beta-lipoprotein fractions returned to near normal after treatment, the proteinuria diminished and serum albumen became normal. Most of these patients did not need any treatment for hyperlipidemia."}
{"id": "PMID:190995", "title": "A nonproducer T lymphoblastoid cell line from Marek's disease transplantable tumor (JMV).", "content": "A continuous lymphoblastoid cell line was established from a JMV tumor transplant related to Marek's disease (MD). It is designated RPL1 (JMV) lymphoblastoid cell line. This cell line contains DNA sequences complementary to MD virus DNA and has an antigen similar to MD-tumor-associated surface antigen (MATSA). However, it lacks any MD virus (MDV) rescuable in vivo or in vitro. The cell line has surface antigens typical of chicken thymus cells (T cells) and histocompatability antigens different from those of the host chicken.", "contents": "A nonproducer T lymphoblastoid cell line from Marek's disease transplantable tumor (JMV). A continuous lymphoblastoid cell line was established from a JMV tumor transplant related to Marek's disease (MD). It is designated RPL1 (JMV) lymphoblastoid cell line. This cell line contains DNA sequences complementary to MD virus DNA and has an antigen similar to MD-tumor-associated surface antigen (MATSA). However, it lacks any MD virus (MDV) rescuable in vivo or in vitro. The cell line has surface antigens typical of chicken thymus cells (T cells) and histocompatability antigens different from those of the host chicken."}
{"id": "PMID:190996", "title": "Pathogenesis of abnormal feathers in chickens inoculated with reticuloendotheliosis virus.", "content": "Abnormal feathers, characterized by thinness and increased transparency of the calamus and rachis, and loss of barbs, were induced at a high frequency by inoculating day-old chicks with reticuloendotheliosis virus (REV) propagated in chicken-embryo fibroblast (CEF) cultures. The few birds that survived inoculation with oncogenic stock of REV derived from liver tissue of an infected chick developed similar abnormalities. Lesions of an inflammatory-degenerative type were observed in close association with the presence of viral antigen and numerous c-type virus particles, characteristic of REV, in the intermediate and cylindrical cell layers of all abnormal feathers examined. These findings, first detected in the intermediate and cylindrical cell layers of developing feathers 6--9 days after infection, suggest that degeneration and necrosis of feather-forming cells result from productive infection of REV, resulting in the development of the abnormal feathers.", "contents": "Pathogenesis of abnormal feathers in chickens inoculated with reticuloendotheliosis virus. Abnormal feathers, characterized by thinness and increased transparency of the calamus and rachis, and loss of barbs, were induced at a high frequency by inoculating day-old chicks with reticuloendotheliosis virus (REV) propagated in chicken-embryo fibroblast (CEF) cultures. The few birds that survived inoculation with oncogenic stock of REV derived from liver tissue of an infected chick developed similar abnormalities. Lesions of an inflammatory-degenerative type were observed in close association with the presence of viral antigen and numerous c-type virus particles, characteristic of REV, in the intermediate and cylindrical cell layers of all abnormal feathers examined. These findings, first detected in the intermediate and cylindrical cell layers of developing feathers 6--9 days after infection, suggest that degeneration and necrosis of feather-forming cells result from productive infection of REV, resulting in the development of the abnormal feathers."}
{"id": "PMID:190997", "title": "Effect of maternal antibody on experimental infections of chickens with a type-8 avian adenovirus.", "content": "Mortality was 60% when chickens without detectable maternal antibody to avian adenoviruses were inoculated intra-abdominally with 10(6) plaque-forming units of AMG 5(2a), a type-8 avian adenovirus. Other results were macroscopic and microscopic lesions in a wide range of organs, statistically significant depression of body weights, AMG 5(2a) virus in the liver and feces, and high virus-neutralizing antibody titers to AMG 5(2a). The disease produced was similar to that described in a previous report of AMG 5(2a) infection of chickens, and similar to inclusion body hepatitis as described in the literature. In contrast, similar inoculation of chickens with maternal antibody to type-8 avian adenovirus resulted in no mortality, lesions in the liver only, no depression of body weight, AMG 5(2a) virus in the feces only, and relatively low virus-neutralizing antibody titers. During this study a hemorrhagic-aplastic anemia syndrome occurred in both AMG 5(2a)-inoculated and control chickens in one trial. Pathologic, virologic, and serologic findings indicated that the spontaneously occurring disease was not caused by an avian adenovirus.", "contents": "Effect of maternal antibody on experimental infections of chickens with a type-8 avian adenovirus. Mortality was 60% when chickens without detectable maternal antibody to avian adenoviruses were inoculated intra-abdominally with 10(6) plaque-forming units of AMG 5(2a), a type-8 avian adenovirus. Other results were macroscopic and microscopic lesions in a wide range of organs, statistically significant depression of body weights, AMG 5(2a) virus in the liver and feces, and high virus-neutralizing antibody titers to AMG 5(2a). The disease produced was similar to that described in a previous report of AMG 5(2a) infection of chickens, and similar to inclusion body hepatitis as described in the literature. In contrast, similar inoculation of chickens with maternal antibody to type-8 avian adenovirus resulted in no mortality, lesions in the liver only, no depression of body weight, AMG 5(2a) virus in the feces only, and relatively low virus-neutralizing antibody titers. During this study a hemorrhagic-aplastic anemia syndrome occurred in both AMG 5(2a)-inoculated and control chickens in one trial. Pathologic, virologic, and serologic findings indicated that the spontaneously occurring disease was not caused by an avian adenovirus."}
{"id": "PMID:190994", "title": "Involvement of a type-8 avian adenovirus in the etiology of inclusion body hepatitis.", "content": "Type-8 avian adenoviruses were isolated from chickens in a commerical flock suffering an outbreak of inclusion body hepatitis. Serum-neutralizing titer to this type, but not to 7 other types of avian adenovirus, was more than 4 times as high in convalescing chickens as in chickens from the flock bled 2 weeks previously, during the disease outbreak. A disease similar to that in the commercial flock and to inclusion body hepatitis as described in the literature was produced by intra-abdominal inoculation of a type-8 isolant, AMG 5 (2a), into 1-day-old specific-pathogen-free chicks. Pathologic features of the disease included necrotizing hepatitis, pancreatitis, and severe lymphoid depletion of the bursa of Fabricius, thymus, and spleen. It was concluded that type-8 avian adenoviruses were involved in the etiology of the naturally occurring outbreak of inclusion body hepatitis.", "contents": "Involvement of a type-8 avian adenovirus in the etiology of inclusion body hepatitis. Type-8 avian adenoviruses were isolated from chickens in a commerical flock suffering an outbreak of inclusion body hepatitis. Serum-neutralizing titer to this type, but not to 7 other types of avian adenovirus, was more than 4 times as high in convalescing chickens as in chickens from the flock bled 2 weeks previously, during the disease outbreak. A disease similar to that in the commercial flock and to inclusion body hepatitis as described in the literature was produced by intra-abdominal inoculation of a type-8 isolant, AMG 5 (2a), into 1-day-old specific-pathogen-free chicks. Pathologic features of the disease included necrotizing hepatitis, pancreatitis, and severe lymphoid depletion of the bursa of Fabricius, thymus, and spleen. It was concluded that type-8 avian adenoviruses were involved in the etiology of the naturally occurring outbreak of inclusion body hepatitis."}
{"id": "PMID:191035", "title": "[Chemotherapeutic activity of ifosfamide in 6 different isologously transplanted experimental tumours of BD-rats (author's transl)].", "content": "The chemotherapeutic activity of ifosfamide, applied i.v. at a high single dose, was tested on some transplantable tumours of BD-rats. As standard substance cyclophosphamide was used. The margin of safety of ifosfamide in DS-carcinosarcoma and TA-nephroblastoma was found to be wider than that of cyclophosphamide. Therefore, using massive single doses of ifosfamide, rats could be cured of DS-carcinosarcoma in higher percentage than by an analogous treatment with cyclophosphamide. Further, with a single i.v. dose of 280 mg/kg ifosfamide was it possible to cure all TA-nephroblastoma-bearing animals. The ANH-nephroblastoma, however, could not be cured even with the highest tolerable doses of ifosfamide. It was, nevertheless, possible to attain higher increase of life span over the controls than by cyclophosphamide-treatment. In some other isologous tumours ifosfamide proved to be less effective or without any activity, respectively. Pretreatment by repeated small doses of ifosfamide resulted in resistance of DS-carcinosarcoma against curative action of subsequent high single doses of this drug.", "contents": "[Chemotherapeutic activity of ifosfamide in 6 different isologously transplanted experimental tumours of BD-rats (author's transl)]. The chemotherapeutic activity of ifosfamide, applied i.v. at a high single dose, was tested on some transplantable tumours of BD-rats. As standard substance cyclophosphamide was used. The margin of safety of ifosfamide in DS-carcinosarcoma and TA-nephroblastoma was found to be wider than that of cyclophosphamide. Therefore, using massive single doses of ifosfamide, rats could be cured of DS-carcinosarcoma in higher percentage than by an analogous treatment with cyclophosphamide. Further, with a single i.v. dose of 280 mg/kg ifosfamide was it possible to cure all TA-nephroblastoma-bearing animals. The ANH-nephroblastoma, however, could not be cured even with the highest tolerable doses of ifosfamide. It was, nevertheless, possible to attain higher increase of life span over the controls than by cyclophosphamide-treatment. In some other isologous tumours ifosfamide proved to be less effective or without any activity, respectively. Pretreatment by repeated small doses of ifosfamide resulted in resistance of DS-carcinosarcoma against curative action of subsequent high single doses of this drug."}
{"id": "PMID:191036", "title": "Tropine derivatives with central activities. Part II: Solvolysis of N-substituted nortropine methanesulfonates.", "content": "The preparation and the reaction kinetical properties in solvolysis of a series of N-substituted nortropine methanesulfonates 1-8 are described. It was found that the rate of solvolysis depends on the nature of the N-substituents considerably. The solvolysis rates can be brought into correlation with the electron donating and withdrawing and steric properties of the N-substituents. Methane-sulfonates of other two bicyclic aminoalcohols 10, 11 were also prepared and kinetically studied.", "contents": "Tropine derivatives with central activities. Part II: Solvolysis of N-substituted nortropine methanesulfonates. The preparation and the reaction kinetical properties in solvolysis of a series of N-substituted nortropine methanesulfonates 1-8 are described. It was found that the rate of solvolysis depends on the nature of the N-substituents considerably. The solvolysis rates can be brought into correlation with the electron donating and withdrawing and steric properties of the N-substituents. Methane-sulfonates of other two bicyclic aminoalcohols 10, 11 were also prepared and kinetically studied."}
{"id": "PMID:191037", "title": "[Novel Bis-sulfonic Acid Esters with Cytostatic Activity (author's transl)].", "content": "The introduction of electron-withdrawing groups into the group R of piposulfan analogs R--SO2--O--X--O--SO2--R substantially increases their antileukemic activity in animal tests (leukemia L 1210). The central moiety X can be varied considerably (provided it contains amide groups) without appreciable loss of activity. A number of busulfan analogs as well as busulfan itself proved to be practically inactive against murine leukemia L 1210. Among a total of 122 bis-sulfonic acid esters tested 35 gave a survival time index of 150% or more after i.p. application and 5 after oral application.", "contents": "[Novel Bis-sulfonic Acid Esters with Cytostatic Activity (author's transl)]. The introduction of electron-withdrawing groups into the group R of piposulfan analogs R--SO2--O--X--O--SO2--R substantially increases their antileukemic activity in animal tests (leukemia L 1210). The central moiety X can be varied considerably (provided it contains amide groups) without appreciable loss of activity. A number of busulfan analogs as well as busulfan itself proved to be practically inactive against murine leukemia L 1210. Among a total of 122 bis-sulfonic acid esters tested 35 gave a survival time index of 150% or more after i.p. application and 5 after oral application."}
{"id": "PMID:191038", "title": "[Cardioprotection by oral application of the calcium antagonist fendiline. Prevention of isoproterenol-induced myocardial necroses in rats (author's transl)].", "content": "1. N-(2-Benzhydryl-ethyl)-N-(1-phenyl-ethyl)-amine hydrochloride (fendiline, Sensit) -- in accordance with its characteristics as a Ca++-antagonist -- shows a strong cardioprotective effect in rats against isoproterenol-induced myocardial necroses. 2. Fendiline is effective via oral administration. 3. The protective effect of fendiline on the myocardium is demonstrated by means of histopathological and histoenzymatic techniques. 4. A particularly reliable method of quantifying the cardio-protective effect of a drug has proven to be the measurement of mitochondrial enzyme activity (cytochrome oxidase, succinate dehydrogenase) using histoenzymatic microphotometry.", "contents": "[Cardioprotection by oral application of the calcium antagonist fendiline. Prevention of isoproterenol-induced myocardial necroses in rats (author's transl)]. 1. N-(2-Benzhydryl-ethyl)-N-(1-phenyl-ethyl)-amine hydrochloride (fendiline, Sensit) -- in accordance with its characteristics as a Ca++-antagonist -- shows a strong cardioprotective effect in rats against isoproterenol-induced myocardial necroses. 2. Fendiline is effective via oral administration. 3. The protective effect of fendiline on the myocardium is demonstrated by means of histopathological and histoenzymatic techniques. 4. A particularly reliable method of quantifying the cardio-protective effect of a drug has proven to be the measurement of mitochondrial enzyme activity (cytochrome oxidase, succinate dehydrogenase) using histoenzymatic microphotometry."}
{"id": "PMID:191039", "title": "Biochemical effects of ethyl apovincaminate.", "content": "Some cerebrobiochemical effects of a new cerebrovasodilatory agent, ethyl apovincaminate (RGH-4405, Cavinton) have been studied. Changes of biogenic amines, 5-hydroxyindole acetic acid (5-HIAA) levels, serotonin (5-HT) turnover rate, furthermore effect on 3',5'-cyclic nucleotide phosphodiesterase (PDE; E.C.3.1.4.c) activity, isolated from different tissues, were determined. Lasting increase of cerebral 5-HIAA level was observed after treatment with the compound, 5-HT levels were transitorily enhanced 2 h following i.p. treatment. At later periods (4-6h) after treatment catecholamine levels were significantly raised. 5-HT turnover was practically uninfluenced by the compound. Activities of PDE preparations isolated from cerebral tissues were markedly inhibited. Various hypotheses are suggested in order to explain the biochemical mechanism of action of the compound.", "contents": "Biochemical effects of ethyl apovincaminate. Some cerebrobiochemical effects of a new cerebrovasodilatory agent, ethyl apovincaminate (RGH-4405, Cavinton) have been studied. Changes of biogenic amines, 5-hydroxyindole acetic acid (5-HIAA) levels, serotonin (5-HT) turnover rate, furthermore effect on 3',5'-cyclic nucleotide phosphodiesterase (PDE; E.C.3.1.4.c) activity, isolated from different tissues, were determined. Lasting increase of cerebral 5-HIAA level was observed after treatment with the compound, 5-HT levels were transitorily enhanced 2 h following i.p. treatment. At later periods (4-6h) after treatment catecholamine levels were significantly raised. 5-HT turnover was practically uninfluenced by the compound. Activities of PDE preparations isolated from cerebral tissues were markedly inhibited. Various hypotheses are suggested in order to explain the biochemical mechanism of action of the compound."}
{"id": "PMID:191042", "title": "Preliminary studies of nonvirion antigens associated with herpes simplex virus 1 and 2 (HSV1 - HSV2).", "content": "Biochemical and radioimmunological studies have indicated the presence of a nonvirion antigen associated with herpes virus. Guinea pig kidney cells were grown in culture and infected (I-cells) for 3h with herpes virus. Uninfected cells (N-cells) served as control. The cells were collected and sonicated to obtain, after centrifugation, \"soluble extract\" (SI, SN). The pellets were extracted with KCl (ISP, NSP). SN, SI were submitted to gel-filtration on Sephadex G-200. Extracts from I and N cells gave similar patterns. After labelling with 125I, greater resolution was obtained in a second gel-filtration with a much smaller load. ISP contained protein species not present in NSP. Polyacrylamide gel electrophoresis of peaks from SN and SI showed that SI contained some radioactive bands not found in SN. Labelled materials from SI and SN were incubated with sera from cancer patients and normal subjects. No differences in binding were seen with SN, but SI showed 14-30% more 125I binding with sera of cancer patients than with sera from normal subjects. No such difference was seen between ISP and NSP.", "contents": "Preliminary studies of nonvirion antigens associated with herpes simplex virus 1 and 2 (HSV1 - HSV2). Biochemical and radioimmunological studies have indicated the presence of a nonvirion antigen associated with herpes virus. Guinea pig kidney cells were grown in culture and infected (I-cells) for 3h with herpes virus. Uninfected cells (N-cells) served as control. The cells were collected and sonicated to obtain, after centrifugation, \"soluble extract\" (SI, SN). The pellets were extracted with KCl (ISP, NSP). SN, SI were submitted to gel-filtration on Sephadex G-200. Extracts from I and N cells gave similar patterns. After labelling with 125I, greater resolution was obtained in a second gel-filtration with a much smaller load. ISP contained protein species not present in NSP. Polyacrylamide gel electrophoresis of peaks from SN and SI showed that SI contained some radioactive bands not found in SN. Labelled materials from SI and SN were incubated with sera from cancer patients and normal subjects. No differences in binding were seen with SN, but SI showed 14-30% more 125I binding with sera of cancer patients than with sera from normal subjects. No such difference was seen between ISP and NSP."}
{"id": "PMID:191043", "title": "Adenosine triphosphatase activity in myxoviruses.", "content": "Sendai and PR 8 viral particles show Na+-K+-ATPase activity, an enzymatic activity which is assumed to be a typical plasma membrane marker and which probably derives from the host cell membrane. Attention has been paid to the peculiar behaviour of Na+-K+-ATPase activity in the two viral strains upon hypoosmotic treatment: Sendai viral particles show enzymatic activity only after swelling, when for PR 8 particles the reverse is true. The results obtained are discussed as suggesting a different organization in the envelope of the viral strains. This approach is supported also by morphological evidence concerned with the osmotic response of viral particles.", "contents": "Adenosine triphosphatase activity in myxoviruses. Sendai and PR 8 viral particles show Na+-K+-ATPase activity, an enzymatic activity which is assumed to be a typical plasma membrane marker and which probably derives from the host cell membrane. Attention has been paid to the peculiar behaviour of Na+-K+-ATPase activity in the two viral strains upon hypoosmotic treatment: Sendai viral particles show enzymatic activity only after swelling, when for PR 8 particles the reverse is true. The results obtained are discussed as suggesting a different organization in the envelope of the viral strains. This approach is supported also by morphological evidence concerned with the osmotic response of viral particles."}
{"id": "PMID:191044", "title": "Sialic acid content in four cell strains transformed by adenoviruses and/or SV40.", "content": "The sialic acid content in hamster cells primarily transformed by adenovirus was found lower than in cells transformed by papovavirus SV40. Intermediate concentrations were shown in a cell strain transformed by an adenovirus-SV40 hybrid. An adenovirus 19 - transformed cell strain derived from the NIL-2 hamster cell line, adapted to unlimited growth in vitro prior to the exposure to the adenovirus, revealed a high content of sialic acid. The concentration of sialic acid in cells transformed by DNA-viruses may depend both on the transforming virus and on the preceding history of the cell line. The tumors revealed more sialic acid than the in vitro cultures derived from the same cell strains. This finding is discussed.", "contents": "Sialic acid content in four cell strains transformed by adenoviruses and/or SV40. The sialic acid content in hamster cells primarily transformed by adenovirus was found lower than in cells transformed by papovavirus SV40. Intermediate concentrations were shown in a cell strain transformed by an adenovirus-SV40 hybrid. An adenovirus 19 - transformed cell strain derived from the NIL-2 hamster cell line, adapted to unlimited growth in vitro prior to the exposure to the adenovirus, revealed a high content of sialic acid. The concentration of sialic acid in cells transformed by DNA-viruses may depend both on the transforming virus and on the preceding history of the cell line. The tumors revealed more sialic acid than the in vitro cultures derived from the same cell strains. This finding is discussed."}
{"id": "PMID:191045", "title": "[Action of emetine hydrochloride in some experimental viral infections].", "content": "The Authors tested the virulicidal effect of emetine hydrochloride (EH) observed by Fusillo in clinical practice. By adding EH to HE p-2 cellular system, in a concentration such as to cause some inhibition of cellular growth, there is no meaningfull virostatic or virulicidal action against poliovirus, Mahoney's strain. EH, in the same proportion as that employed by Fusillo in human therapy, damages in the albino mouse liver. By halving the concentration of EH such a damage is not evident but no beneficial effect on the pattern of the subacute hepatitis, caused by 5 LD50 of MHV3 ensues.", "contents": "[Action of emetine hydrochloride in some experimental viral infections]. The Authors tested the virulicidal effect of emetine hydrochloride (EH) observed by Fusillo in clinical practice. By adding EH to HE p-2 cellular system, in a concentration such as to cause some inhibition of cellular growth, there is no meaningfull virostatic or virulicidal action against poliovirus, Mahoney's strain. EH, in the same proportion as that employed by Fusillo in human therapy, damages in the albino mouse liver. By halving the concentration of EH such a damage is not evident but no beneficial effect on the pattern of the subacute hepatitis, caused by 5 LD50 of MHV3 ensues."}
{"id": "PMID:191041", "title": "[Intrathoracic tumors in children].", "content": "Intrathoracic tumors in pediatric ages are unfrequent. A review of 138 cases in patients under 15 years of age showed in the first place, the same as in adults, malignant neoplasms represented by pulmonary metastases. However, in those of primary localization, the histologically benign are more frequent. Out of 69 cases, such tumors came up to 78.2% and 47% of them were cystic malformations. Among malignant primary neoplasms, out of 30.4%, neuroblastoma showed 8.6%, diverse sarcomas were 8.6% and the epithelial type added up to 4.3%. The main symptoms were: frequent bronchopulmonary infections, obstructive respiratory insufficiency and vascular stasis. Radiological examinations are of great diagnostic aid, but a full clinical evaluation is always necessary. A surgical treatment removing the mass leads to radical recovery leaving limited sequelae. The comparative group of 69 cases with pulmonary metastases showed that neoplasms considered of embryonal type are practically always multiple and appear during the final stage of the disease. Surgery may be attempted when they are single and the primary has been removed; however, chemotherapy and radiotherapy are always necessary.", "contents": "[Intrathoracic tumors in children]. Intrathoracic tumors in pediatric ages are unfrequent. A review of 138 cases in patients under 15 years of age showed in the first place, the same as in adults, malignant neoplasms represented by pulmonary metastases. However, in those of primary localization, the histologically benign are more frequent. Out of 69 cases, such tumors came up to 78.2% and 47% of them were cystic malformations. Among malignant primary neoplasms, out of 30.4%, neuroblastoma showed 8.6%, diverse sarcomas were 8.6% and the epithelial type added up to 4.3%. The main symptoms were: frequent bronchopulmonary infections, obstructive respiratory insufficiency and vascular stasis. Radiological examinations are of great diagnostic aid, but a full clinical evaluation is always necessary. A surgical treatment removing the mass leads to radical recovery leaving limited sequelae. The comparative group of 69 cases with pulmonary metastases showed that neoplasms considered of embryonal type are practically always multiple and appear during the final stage of the disease. Surgery may be attempted when they are single and the primary has been removed; however, chemotherapy and radiotherapy are always necessary."}
{"id": "PMID:191046", "title": "[Human seroepidemiology Polyoma virus BK in Umbria].", "content": "A serological study on the antibody level against BK virus in healthy population and respiratory patients in Umbria was performed. Serum samples of 465 healthy people and 155 patients grouped by age, were tested using HAI. 47% of all sera was positive. The epidemiological implications are discussed.", "contents": "[Human seroepidemiology Polyoma virus BK in Umbria]. A serological study on the antibody level against BK virus in healthy population and respiratory patients in Umbria was performed. Serum samples of 465 healthy people and 155 patients grouped by age, were tested using HAI. 47% of all sera was positive. The epidemiological implications are discussed."}
{"id": "PMID:191047", "title": "Prevalence in the Rome healthy population of antibodies to a human Polyoma - virus (BK - strain).", "content": "A serological study of determine the prevalence of infections caused by human Polyoma-virus (BK strain) among the healthy population of Rome has been performed. Such virus was originally isolated from a patient undergoing a kidney transplantation, and later found in patients undergoing immunosuppressive therapy. Previous serological studies showed high incidences of infections, caused by this virus, in human populations. Other viruses, antigenically related, were found in patients suffering from progressive multifocal leukoencephalopathy. Serum samples coming from 482 healthy subjects classified by age and 100 cord blood serum samples were analyzed for antibody titers using haemoagglutination-inhibition and complement fixation tests. High incidence of infection caused by BK virus in the Roman population was found: specifically the haeomagglutination-inhibition test resulted positive in 65.2% of the samples. A remarkable similar trend between the results obtained with both the techniques was observed, although differences in antibody serum levels were present. The infections, which are not transmitted during the intrauterine life, are first noted at about two years of age. The Authors finally briefly discuss the possible epidemiological meaning of the spreading of this infection.", "contents": "Prevalence in the Rome healthy population of antibodies to a human Polyoma - virus (BK - strain). A serological study of determine the prevalence of infections caused by human Polyoma-virus (BK strain) among the healthy population of Rome has been performed. Such virus was originally isolated from a patient undergoing a kidney transplantation, and later found in patients undergoing immunosuppressive therapy. Previous serological studies showed high incidences of infections, caused by this virus, in human populations. Other viruses, antigenically related, were found in patients suffering from progressive multifocal leukoencephalopathy. Serum samples coming from 482 healthy subjects classified by age and 100 cord blood serum samples were analyzed for antibody titers using haemoagglutination-inhibition and complement fixation tests. High incidence of infection caused by BK virus in the Roman population was found: specifically the haeomagglutination-inhibition test resulted positive in 65.2% of the samples. A remarkable similar trend between the results obtained with both the techniques was observed, although differences in antibody serum levels were present. The infections, which are not transmitted during the intrauterine life, are first noted at about two years of age. The Authors finally briefly discuss the possible epidemiological meaning of the spreading of this infection."}
{"id": "PMID:191050", "title": "Ultrastructural studies of epidermal lesions in pityriasis lichenoides chronica: occurrence of tubular aggregates and intracytoplasmic desmosomes.", "content": "Very early skin lesions from four patients with pityriasis lichenoides chronica were examined by electron microscopy. Aggregates of tubular structures, which resembled those reported in endothelium in lupus erythematosus and are currently being observed in an increasing variety of conditions, were noticed in the epidermal cells of all patients. These cells also showed intracytoplasmic desmosomes, and isolated mitochondria and myelin-like figures in intercellular spaces, in addition to the occurrence of vacuoles and lysosomes in the cytoplasm, dilatation of endoplasmic reticulum and alteration of mitochondria. Occasionally, epidermal cells were seen to be individually filled with fibrils. These ultrastructural findings seem to indicate that in pityriasis lichenoides chronica some injury to epidermal cells occurs at the early stage of pathological processes, as suggested by light microscope studies.", "contents": "Ultrastructural studies of epidermal lesions in pityriasis lichenoides chronica: occurrence of tubular aggregates and intracytoplasmic desmosomes. Very early skin lesions from four patients with pityriasis lichenoides chronica were examined by electron microscopy. Aggregates of tubular structures, which resembled those reported in endothelium in lupus erythematosus and are currently being observed in an increasing variety of conditions, were noticed in the epidermal cells of all patients. These cells also showed intracytoplasmic desmosomes, and isolated mitochondria and myelin-like figures in intercellular spaces, in addition to the occurrence of vacuoles and lysosomes in the cytoplasm, dilatation of endoplasmic reticulum and alteration of mitochondria. Occasionally, epidermal cells were seen to be individually filled with fibrils. These ultrastructural findings seem to indicate that in pityriasis lichenoides chronica some injury to epidermal cells occurs at the early stage of pathological processes, as suggested by light microscope studies."}
{"id": "PMID:191052", "title": "ACTH levels in maternal, fetal and neonatal plasma after short-term prenatal dexamethasone therapy.", "content": "The effect of prenatal dexamethasone therapy (12, 8 and 4 mg doses given intramuscularly on three consecutive days) on ACTH levels in maternal plasma (n=33), mixed umbilical cord plasma (n=31) and plasma from the newborn (n=29) was studied, and the results were compared with those obtained in 56 healthy parturients and 50 of their newborn. Maternal ACTH after delivery was significantly lower in the mothers treated with dexamethasone than in the control group. Cord ACTH values were similar in the two groups. ACTH levels fell during the early neonatal period, but only at 12 to 24 hours were the ACTH levels significantly lower in the dexamethasone group than in the controls. Gestational age, birth weight and the interval between the dexamethasone therapy and delivery had no significant effect on cord ACTH levels. Short-term prenatal dexamethasone therapy seemed to have very little effect on ACTH secretion in the mother, in the fetus and in the newborn.", "contents": "ACTH levels in maternal, fetal and neonatal plasma after short-term prenatal dexamethasone therapy. The effect of prenatal dexamethasone therapy (12, 8 and 4 mg doses given intramuscularly on three consecutive days) on ACTH levels in maternal plasma (n=33), mixed umbilical cord plasma (n=31) and plasma from the newborn (n=29) was studied, and the results were compared with those obtained in 56 healthy parturients and 50 of their newborn. Maternal ACTH after delivery was significantly lower in the mothers treated with dexamethasone than in the control group. Cord ACTH values were similar in the two groups. ACTH levels fell during the early neonatal period, but only at 12 to 24 hours were the ACTH levels significantly lower in the dexamethasone group than in the controls. Gestational age, birth weight and the interval between the dexamethasone therapy and delivery had no significant effect on cord ACTH levels. Short-term prenatal dexamethasone therapy seemed to have very little effect on ACTH secretion in the mother, in the fetus and in the newborn."}
{"id": "PMID:191054", "title": "Epidemic keratoconjunctivitis and chronic papillary conjunctivitis in London due to adenovirus type 19.", "content": "Since July 1973 cases of keratoconjunctivitis resembling epidemic keratoconjunctivitis were observed in the External Eye Disease Clinic at Moorfields Eye Hospital; City Road, London. Adenovirus type 19 was isolated in human embryonic kidney cells from 21 patients. The majority were males between 20 and 40 years old. A small hospital outbreak involving six patients occurred. Clinical features of the disease, consisting of moderate to severe follicular conjunctivitis, major subepithelial punctate keratitis, sometimes with pseudomembrane and scarring, were closely similar to those of epidemic keratoconjunctivitis caused by adenovirus type 8. This similarity, as well as the ability of the agent to cause hospital outbreaks, indicates that adenovirus type 19 is a cause of epidemic keratoconjunctivitis. A case of bilateral chronic papillary conjunctivitis that persisted for 16 months following an acute onset was described. Adeno 19 was isolated from the eye of the patient after 12 months of recrudescent or recurrent illness. Chronic adenovirus infection lacking the usual clinical picture of an acute follicular reaction has not hitherto been described. Such cases are probably important because of the obvious danger of continuing the carriage and shedding of infective adeno 19 from one outbreak to another, by presenting subsequently in eye clinics, and providing an unrecognised source of infection to initiate further outbreaks of hospital transmission.", "contents": "Epidemic keratoconjunctivitis and chronic papillary conjunctivitis in London due to adenovirus type 19. Since July 1973 cases of keratoconjunctivitis resembling epidemic keratoconjunctivitis were observed in the External Eye Disease Clinic at Moorfields Eye Hospital; City Road, London. Adenovirus type 19 was isolated in human embryonic kidney cells from 21 patients. The majority were males between 20 and 40 years old. A small hospital outbreak involving six patients occurred. Clinical features of the disease, consisting of moderate to severe follicular conjunctivitis, major subepithelial punctate keratitis, sometimes with pseudomembrane and scarring, were closely similar to those of epidemic keratoconjunctivitis caused by adenovirus type 8. This similarity, as well as the ability of the agent to cause hospital outbreaks, indicates that adenovirus type 19 is a cause of epidemic keratoconjunctivitis. A case of bilateral chronic papillary conjunctivitis that persisted for 16 months following an acute onset was described. Adeno 19 was isolated from the eye of the patient after 12 months of recrudescent or recurrent illness. Chronic adenovirus infection lacking the usual clinical picture of an acute follicular reaction has not hitherto been described. Such cases are probably important because of the obvious danger of continuing the carriage and shedding of infective adeno 19 from one outbreak to another, by presenting subsequently in eye clinics, and providing an unrecognised source of infection to initiate further outbreaks of hospital transmission."}
{"id": "PMID:191055", "title": "Pleomorphic adenoma of the nasal septum.", "content": "A brief review of the world literature on pleomorphic adenoma of the nasal septum is presented. One further case is reported, treated by surgical excision via lateral rhinotomy. Alternative surgical approaches are considered.", "contents": "Pleomorphic adenoma of the nasal septum. A brief review of the world literature on pleomorphic adenoma of the nasal septum is presented. One further case is reported, treated by surgical excision via lateral rhinotomy. Alternative surgical approaches are considered."}
{"id": "PMID:191056", "title": "The enhancement by dietary zinc deficiency of the susceptibility of the rat duodenum to colchicine.", "content": "1. The incidence of colchicine-induced lesions in the germinal epithelium oof the rat duodenum was studied in young rats in an early stage of zinc deficiency and in their pair-fed controls. At both dose levels of colchicine used, a marked increase in the amount of cell damage was observed in the duodenum of Zn-deficient rats as compared with the pair-fed, control (Zn-supplemented) rats. 2. No statistical interaction between Zn and colchicine was demonstrable, and no lesions were found in the duodenum of animals that had not been treated with colchicine. 3. The results are discussed in relation to the effects of Zn deficiency in animals and the possible involvement of Zn in the maintenance of the integrity of microtubular structures.", "contents": "The enhancement by dietary zinc deficiency of the susceptibility of the rat duodenum to colchicine. 1. The incidence of colchicine-induced lesions in the germinal epithelium oof the rat duodenum was studied in young rats in an early stage of zinc deficiency and in their pair-fed controls. At both dose levels of colchicine used, a marked increase in the amount of cell damage was observed in the duodenum of Zn-deficient rats as compared with the pair-fed, control (Zn-supplemented) rats. 2. No statistical interaction between Zn and colchicine was demonstrable, and no lesions were found in the duodenum of animals that had not been treated with colchicine. 3. The results are discussed in relation to the effects of Zn deficiency in animals and the possible involvement of Zn in the maintenance of the integrity of microtubular structures."}
{"id": "PMID:191057", "title": "Analysis of the defect structure of gel-phase lipid.", "content": "The partitioning of the spin label 2,2,6,6-tetramethylpiperidinyl-1-oxy (Tempo) into phosphatidylcholine bilayers and the monomer-aggregate equilibrium for chlorophyll a incorporated into phosphatidylcholine bilayers have been interpreted in terms of the formation of defects in the gel-phase lipid, starting some 20 degrees C below the temperature of the main gel to liquid crystalline phase transition. By contrast, defects seem to be largely absent from bilayers of dipalmitoylphosphatidylethanolamine in the gel phase. The defect structure accounts for the continuous nature of the phase transition for phosphatidylcholines, and also for the increase in width of the transition caused by the addition of alcohols.", "contents": "Analysis of the defect structure of gel-phase lipid. The partitioning of the spin label 2,2,6,6-tetramethylpiperidinyl-1-oxy (Tempo) into phosphatidylcholine bilayers and the monomer-aggregate equilibrium for chlorophyll a incorporated into phosphatidylcholine bilayers have been interpreted in terms of the formation of defects in the gel-phase lipid, starting some 20 degrees C below the temperature of the main gel to liquid crystalline phase transition. By contrast, defects seem to be largely absent from bilayers of dipalmitoylphosphatidylethanolamine in the gel phase. The defect structure accounts for the continuous nature of the phase transition for phosphatidylcholines, and also for the increase in width of the transition caused by the addition of alcohols."}
{"id": "PMID:191058", "title": "Fluidity of the lipids next to the acetylcholine receptor protein of torpedo membrane fragments. Use of amphiphilic reversible spin-labels.", "content": "Choline esters of spin-labeled fatty acids (long-chain acylcholines) were used to probe the hydrophobic environment of the acetylcholine receptor protein in membrane fragments from Torpedo marmorata. These spin-labels competitively inhibit the binding of [3H]acetylcholine to the receptor site. Their inhibition constants (KI) were close to 200 nM. At the high membrane concentration required for electron spin resonance (ESR) experiments, the apparent inhibition constants (KIapp) differed from KI determined by using dilute membrane concentration. This is due to the amphiphilic character of long-chain acylcholine. For most spin-labels used, only difference ESR spectroscopy provided reliable spectra corresponding to receptor-bound spin-labeled acylcholines. Acetylcholine receptor agonists and antagonists displaced the acylcholine from the receptor sites, whereas choline had only a weak effect. This produced a modification in the ESR spectra of the bound acylcholines and provided evidence that the acylcholines bound to the receptor sites in a specific manner. The interpretation of the spectra of receptor-bound spin-labels favored a strong barrier to the motion of the probe when attached to the middle of the acyl chain. However, when the probe was close to the methyl terminal of a stearoylcholine molecule a much greater fluidity was found. Short-range spin-spin interactions were created between spin-labels bound to the receptor site and spin-labels in a fluid phase. This indicates that lipids next to the receptor protein are not completely immobilized in spite of the semicrystalline organization of the proteins in the postsynaptic region.", "contents": "Fluidity of the lipids next to the acetylcholine receptor protein of torpedo membrane fragments. Use of amphiphilic reversible spin-labels. Choline esters of spin-labeled fatty acids (long-chain acylcholines) were used to probe the hydrophobic environment of the acetylcholine receptor protein in membrane fragments from Torpedo marmorata. These spin-labels competitively inhibit the binding of [3H]acetylcholine to the receptor site. Their inhibition constants (KI) were close to 200 nM. At the high membrane concentration required for electron spin resonance (ESR) experiments, the apparent inhibition constants (KIapp) differed from KI determined by using dilute membrane concentration. This is due to the amphiphilic character of long-chain acylcholine. For most spin-labels used, only difference ESR spectroscopy provided reliable spectra corresponding to receptor-bound spin-labeled acylcholines. Acetylcholine receptor agonists and antagonists displaced the acylcholine from the receptor sites, whereas choline had only a weak effect. This produced a modification in the ESR spectra of the bound acylcholines and provided evidence that the acylcholines bound to the receptor sites in a specific manner. The interpretation of the spectra of receptor-bound spin-labels favored a strong barrier to the motion of the probe when attached to the middle of the acyl chain. However, when the probe was close to the methyl terminal of a stearoylcholine molecule a much greater fluidity was found. Short-range spin-spin interactions were created between spin-labels bound to the receptor site and spin-labels in a fluid phase. This indicates that lipids next to the receptor protein are not completely immobilized in spite of the semicrystalline organization of the proteins in the postsynaptic region."}
{"id": "PMID:191059", "title": "Reaction of essential lysyl residues of pig heart diphosphyridine nucleotide dependent isocitrate dehydrogenase with 2,4-pentanedione.", "content": "The rate of inactivation of pig heart DPN-specific isocitrate dehydrogenase by 2,4-pentanedione is pseudo-first-order and linearly dependent on reagent concentration. Isocitrate incombination with manganous ion can prevent inactivation, and a dissociation constant (KIC) for the enzyme-isocitrate complex can be calculated which is similar in magnitude to the Km for isocitrate under the same conditions. Although neither the cofactor,DPN, nor the allosteric activator, ADP, prevents inactivation by reagent, ADP lowers both KIC and Km to the same extent. These data suggest that the reagent may be reacting with residues within a binding site for manganeous-isocitrate. DPNH accelerates the inactivation and also enhances protection by isocitrate, lowering KIC by a factor of 20. Because ADP does not prevent the DPNH rate enhancement, it is unlikely that the two nucleotides compete for identical binding sites. Reaction with 2,4-pentanedione thus provides a probe of the mode of ligand interaction with the enzyme. Inactivation appears to result from the reaction of 2,4-pentanedione with lysyl residues to form enamines. The occurrence of a new absorbance band during inactivation and the isolation by gel filtration of enzyme with an absorbance peak at 312 nm are consistent with enamine formation. Hydroxylamine, which abolishes the 312-nm peak, also causes appreciable reactivation of the enzyme. By use of [2,4-14C]-2,4-pentanedione, it was established that reaction of an average of no more than 3 lysines of the 26 per peptide chain resulted in complete inactivation; and an average of only 2 lysines react when enzymatic activity is retained in the presence of 50 mM isocitrate. Reaction with arginine was excluded by the unchanged amino acid composition of modified enzyme. These data suggest that formation of an enamine of possibly 1, and certainly no more than 3, lysine residue(s) in the catalytic center of the enzyme is responsible for inactivation by 2,4-pentanedione.", "contents": "Reaction of essential lysyl residues of pig heart diphosphyridine nucleotide dependent isocitrate dehydrogenase with 2,4-pentanedione. The rate of inactivation of pig heart DPN-specific isocitrate dehydrogenase by 2,4-pentanedione is pseudo-first-order and linearly dependent on reagent concentration. Isocitrate incombination with manganous ion can prevent inactivation, and a dissociation constant (KIC) for the enzyme-isocitrate complex can be calculated which is similar in magnitude to the Km for isocitrate under the same conditions. Although neither the cofactor,DPN, nor the allosteric activator, ADP, prevents inactivation by reagent, ADP lowers both KIC and Km to the same extent. These data suggest that the reagent may be reacting with residues within a binding site for manganeous-isocitrate. DPNH accelerates the inactivation and also enhances protection by isocitrate, lowering KIC by a factor of 20. Because ADP does not prevent the DPNH rate enhancement, it is unlikely that the two nucleotides compete for identical binding sites. Reaction with 2,4-pentanedione thus provides a probe of the mode of ligand interaction with the enzyme. Inactivation appears to result from the reaction of 2,4-pentanedione with lysyl residues to form enamines. The occurrence of a new absorbance band during inactivation and the isolation by gel filtration of enzyme with an absorbance peak at 312 nm are consistent with enamine formation. Hydroxylamine, which abolishes the 312-nm peak, also causes appreciable reactivation of the enzyme. By use of [2,4-14C]-2,4-pentanedione, it was established that reaction of an average of no more than 3 lysines of the 26 per peptide chain resulted in complete inactivation; and an average of only 2 lysines react when enzymatic activity is retained in the presence of 50 mM isocitrate. Reaction with arginine was excluded by the unchanged amino acid composition of modified enzyme. These data suggest that formation of an enamine of possibly 1, and certainly no more than 3, lysine residue(s) in the catalytic center of the enzyme is responsible for inactivation by 2,4-pentanedione."}
{"id": "PMID:191060", "title": "Enzymic hydrolysis of phosphonate esters. Reaction mechanism of intestinal 5'-nucleotide phosphodiesterase.", "content": "The mechanism of bovine intestinal 5'-nucleotide phosphodiesterase was investigated by determining kinetic constants of systematically varied substrates, with emphasis on esters of phosphonic acids (which have much higer Vmax values than conventional phosphodiester substrates), and by pre-steady-state kinetics using bis(4-nitrophenyl) phosphate as substrate. The results suggest a ping-pong type mechanism, with participation of a covalent enzyme intermediate.", "contents": "Enzymic hydrolysis of phosphonate esters. Reaction mechanism of intestinal 5'-nucleotide phosphodiesterase. The mechanism of bovine intestinal 5'-nucleotide phosphodiesterase was investigated by determining kinetic constants of systematically varied substrates, with emphasis on esters of phosphonic acids (which have much higer Vmax values than conventional phosphodiester substrates), and by pre-steady-state kinetics using bis(4-nitrophenyl) phosphate as substrate. The results suggest a ping-pong type mechanism, with participation of a covalent enzyme intermediate."}
{"id": "PMID:191061", "title": "Free radical and ionic reaction of bisulfite with reduced nicotinamide adenine dinucleotide and its analogues.", "content": "1,4-Dihydronicotinamide adenine dinucleotide (NADH) and its analogues undergo two reactions in sulfite buffers in the pH range 5.5-7.1: (1) an oxygen-mediated free-radical chain reaction which results in the oxidation of the dihydropyridine to the pyridinium salt, and (2) an ionic reaction which results in the hydration of the 5,6 double bond of the dihydropyridine. The free-radical reaction is inhibited by superoxide dismutase (indicating the involvement of superoxide radicals) and by free-radical inhibitors. The ionic reaction is not affected by free-radical inhibitors and follows the rate law: rate = [substrate] [HSO3-] (K + SIGMAK' [HA]), where HA is a general acid of hydronium ion. The occurrence of third-order terms of the type [substrate] X [HSO3-] [HA] is consistent with the formation of a reactive bisulfite-substrate complex, which undergoes general acid catalyzed hydration.", "contents": "Free radical and ionic reaction of bisulfite with reduced nicotinamide adenine dinucleotide and its analogues. 1,4-Dihydronicotinamide adenine dinucleotide (NADH) and its analogues undergo two reactions in sulfite buffers in the pH range 5.5-7.1: (1) an oxygen-mediated free-radical chain reaction which results in the oxidation of the dihydropyridine to the pyridinium salt, and (2) an ionic reaction which results in the hydration of the 5,6 double bond of the dihydropyridine. The free-radical reaction is inhibited by superoxide dismutase (indicating the involvement of superoxide radicals) and by free-radical inhibitors. The ionic reaction is not affected by free-radical inhibitors and follows the rate law: rate = [substrate] [HSO3-] (K + SIGMAK' [HA]), where HA is a general acid of hydronium ion. The occurrence of third-order terms of the type [substrate] X [HSO3-] [HA] is consistent with the formation of a reactive bisulfite-substrate complex, which undergoes general acid catalyzed hydration."}
{"id": "PMID:191062", "title": "Complement-induced decrease in membrane mobility: introducing a more sensitive index of spin-label motion.", "content": "We have used spin-labeling to investigate complement-induced changes in lipid organization of antibody-sensitized sheep erythrocyte membranes. The spectrum of methyl 5-doxylstearate incorporated into the lipid component of sheep erythrocyte membranes is typical of a membrane bilayer. The membranes from complement-lysed erythrocytes have a small, but statistically significant, reduction in fluidity when compared to membranes from osmotically-lysed erythrocytes, as indicated by a small increase in T'. In theory, measurements of the widths of the outer hyperfine extrema should be more sensitive to motion than the separation of the outer hyperfine extrema (2T'). Our results indicate that the half-width at half-height of the outer hyperfine extrema show a severalfold greater percentage change than T'. The sign and magnitude of these changes are in general agreement with previous predictions. Our results imply that motional corrections to the S formalism of Hubbell, Gaffney, and McConnell are necessary because spin-label motion appears to be explicitly represented in this type of electron spin resonance spectra.", "contents": "Complement-induced decrease in membrane mobility: introducing a more sensitive index of spin-label motion. We have used spin-labeling to investigate complement-induced changes in lipid organization of antibody-sensitized sheep erythrocyte membranes. The spectrum of methyl 5-doxylstearate incorporated into the lipid component of sheep erythrocyte membranes is typical of a membrane bilayer. The membranes from complement-lysed erythrocytes have a small, but statistically significant, reduction in fluidity when compared to membranes from osmotically-lysed erythrocytes, as indicated by a small increase in T'. In theory, measurements of the widths of the outer hyperfine extrema should be more sensitive to motion than the separation of the outer hyperfine extrema (2T'). Our results indicate that the half-width at half-height of the outer hyperfine extrema show a severalfold greater percentage change than T'. The sign and magnitude of these changes are in general agreement with previous predictions. Our results imply that motional corrections to the S formalism of Hubbell, Gaffney, and McConnell are necessary because spin-label motion appears to be explicitly represented in this type of electron spin resonance spectra."}
{"id": "PMID:191063", "title": "Spin-labeled acyl atractyloside as a probe of the mitochondrial adenosine diphosphate carrier. Asymmetry of the carrier and direct lipid environment.", "content": "A number of spin-labeled acyl derivatives of atractyloside, (m,n)acyl-ATR (general formula: CH3- (CH2)mCX(CH2)nCOO-ATR, where X is an o-azolidine ring containing a nitroxide), have been synthesized. As shown by electron spin resonance (ESR) spectra of spin-labeled acyl-ATR, the nitroxide placed on the acyl chain interacts with the diterpene residue of the atractyloside moiety when incorporated in liposomes. Spin-labeled acyl-ATRs were used to probe the ADP carrier in heart mitochondria. They inhibit ADP transport with the same efficiency as unlabeled acyl-ATRs. The inhibition is a mixed competitive and noncompetitive inhibition. The inhibitor constant is close to 10(-7) M. The long chain acyl-ATRs (10,3)- (7,6)-, (7,8)-, and (5,10)acyl-ATRs) and also the short chain (0,2)acyl-ATR, when added at low concentrations to heart mitochondria, give rise to more immobilized ESR spectra than when added to liposomes. Immobilization is stronger for the first three molecules of the series. The (1,14)acyl-ATR, which possesses a nitroxide almost at the end of the acyl chain near the terminal methyl, gives rise to a spectrum corresponding to a high degree of fluidity. Upon addition of atractyloside or of other specific ligands, spin-labeled long-chain acyl-ATRs bound to the ADP carrier are displaced from their binding site toward the lipid phase of the mitochondrial membrane and the short chain (0,2)acyl-ATR is released into the aqueous phase. Spin-labeled long-chain acyl-ATRs do not show any evidence of binding to a protein when incubated with \"inside out\" submitochondrial particles, in spite of the fact that these particles are able to transport ADP. These results are discussed with respect to the size and the asymmetry of the ADP carrier in the mitochondrial membrane and the mechanism of ADP transport.", "contents": "Spin-labeled acyl atractyloside as a probe of the mitochondrial adenosine diphosphate carrier. Asymmetry of the carrier and direct lipid environment. A number of spin-labeled acyl derivatives of atractyloside, (m,n)acyl-ATR (general formula: CH3- (CH2)mCX(CH2)nCOO-ATR, where X is an o-azolidine ring containing a nitroxide), have been synthesized. As shown by electron spin resonance (ESR) spectra of spin-labeled acyl-ATR, the nitroxide placed on the acyl chain interacts with the diterpene residue of the atractyloside moiety when incorporated in liposomes. Spin-labeled acyl-ATRs were used to probe the ADP carrier in heart mitochondria. They inhibit ADP transport with the same efficiency as unlabeled acyl-ATRs. The inhibition is a mixed competitive and noncompetitive inhibition. The inhibitor constant is close to 10(-7) M. The long chain acyl-ATRs (10,3)- (7,6)-, (7,8)-, and (5,10)acyl-ATRs) and also the short chain (0,2)acyl-ATR, when added at low concentrations to heart mitochondria, give rise to more immobilized ESR spectra than when added to liposomes. Immobilization is stronger for the first three molecules of the series. The (1,14)acyl-ATR, which possesses a nitroxide almost at the end of the acyl chain near the terminal methyl, gives rise to a spectrum corresponding to a high degree of fluidity. Upon addition of atractyloside or of other specific ligands, spin-labeled long-chain acyl-ATRs bound to the ADP carrier are displaced from their binding site toward the lipid phase of the mitochondrial membrane and the short chain (0,2)acyl-ATR is released into the aqueous phase. Spin-labeled long-chain acyl-ATRs do not show any evidence of binding to a protein when incubated with \"inside out\" submitochondrial particles, in spite of the fact that these particles are able to transport ADP. These results are discussed with respect to the size and the asymmetry of the ADP carrier in the mitochondrial membrane and the mechanism of ADP transport."}
{"id": "PMID:191064", "title": "Structural and dynamical aspects of membrane immunochemistry using model membranes.", "content": "Three different phospholipid haptens have been synthesized, in which the haptenic group is the paramagnetic nitroxide (spin-label) group. These lipid haptens differ from one another in the length and composition of the molecular chain linking the 2,2,6,6-tetramethylpiperidinyl-N-oxy moiety to the phosphodiester group of the lipid. These lipid haptens have been incorporated at low molar concentrations (0.01 to 0.5 mol %) in liposomes containing various proportions of cholesterol and dipalmitoylphosphatidylcholine (DPPC). A study has been made of specific antinitroxide IgG (and Fab) binding to these liposomes, and the fixation of complement. From these studies we conclude: (a) For lipid haptens whose possible extension above the bilayer plane is limited (e.g., approximately 10-20 A), antibody binding and complement fixation depend strongly on the hapten structure and host lipid composition, because of steric limitations on the accessibility of lipid haptens to the binding sites in the protein. (b) Complement fixation by specific IgG antibodies directed against the nitroxide group as part of a lipid hapten depends strongly on the lateral mobility of the lipid hapten when its molar concentration in the plane of the membrane is of the order of 0.1 mol % or less. It is likely that this conclusion applies to many lipid haptens, and possibly other membrane components. (c) The inclusion of cholesterol in lipid membranes has at least two distinct effects on complement fixation involving lipid haptens. Through a steric effect on bilayer structure (probably involving lateral molecular ordering) cholesterol in phosphatidylcholine bilayers can enhance hapten exposure to antibody binding sites, enhance antibody binding, and thereby enhance complement fixation. It is likely that cholesterol also affects complement fixation at low hapten concentrations through a modification of membrane fluidity.", "contents": "Structural and dynamical aspects of membrane immunochemistry using model membranes. Three different phospholipid haptens have been synthesized, in which the haptenic group is the paramagnetic nitroxide (spin-label) group. These lipid haptens differ from one another in the length and composition of the molecular chain linking the 2,2,6,6-tetramethylpiperidinyl-N-oxy moiety to the phosphodiester group of the lipid. These lipid haptens have been incorporated at low molar concentrations (0.01 to 0.5 mol %) in liposomes containing various proportions of cholesterol and dipalmitoylphosphatidylcholine (DPPC). A study has been made of specific antinitroxide IgG (and Fab) binding to these liposomes, and the fixation of complement. From these studies we conclude: (a) For lipid haptens whose possible extension above the bilayer plane is limited (e.g., approximately 10-20 A), antibody binding and complement fixation depend strongly on the hapten structure and host lipid composition, because of steric limitations on the accessibility of lipid haptens to the binding sites in the protein. (b) Complement fixation by specific IgG antibodies directed against the nitroxide group as part of a lipid hapten depends strongly on the lateral mobility of the lipid hapten when its molar concentration in the plane of the membrane is of the order of 0.1 mol % or less. It is likely that this conclusion applies to many lipid haptens, and possibly other membrane components. (c) The inclusion of cholesterol in lipid membranes has at least two distinct effects on complement fixation involving lipid haptens. Through a steric effect on bilayer structure (probably involving lateral molecular ordering) cholesterol in phosphatidylcholine bilayers can enhance hapten exposure to antibody binding sites, enhance antibody binding, and thereby enhance complement fixation. It is likely that cholesterol also affects complement fixation at low hapten concentrations through a modification of membrane fluidity."}
{"id": "PMID:191065", "title": "Recognition of different pools of phosphatidylglycerol in intact cells and isolated membranes of Acholeplasma laidlawii by phospholipase A2.", "content": "Phospholipase A2 (EC 3.1.1.4) from pig pancreas hydrolyzes phosphatidylglycerol in intact cells and isolated membranes of Acholeplasma laidlawii. Complete degradation of phosphatidylglycerol in intact cells at 37 degrees C does not result in lysis as shown by the retention of intracellular K+ ions and the cytoplasmic glucose-6-phosphatase, as well as the inability to detect activity of membrane-bound intracellular NADH-oxidase. A. laidlawii was grown on linoleic acid. Phospholipase A2 treatment of these cells at 5 degrees C, at which temperature the lipids are still in the liquid-crystalline state, results in a rapid breakdown of 50% of the phosphatidylglycerol. The residual phosphatidylglycerol can be hydrolyzed only at elevated temperatures and at much smaller rates, depending strongly on the incubation temperature. When membranes isolated from these cells are incubated at 5 degrees C, 70% of the phosphatidylglycerol is hydrolyzed immediately. The hydrolysis of the residual 30% is again strongly temperature dependent. Cells were grown on palmitate, elaidate, or oleate to investigate possible effects of the lipid phase transition on the accessibility of phosphatidylglycerol for phospholipase A2. Under conditions in which all the lipid is in the solid state, no hydrolysis occurs. When solid and liquid-crystalline lipid phases coexist, a limited hydrolysis of phosphatidylglycerol can be observed. The results demonstrate the disposition of phosphatidylglycerol in three different pools in the membrane of A. laidlawii. Phospholipase A2 has been used to discriminate between these pools and to estimate the amount of phosphatidylglycerol which is present in the liquid-crystalline phase. The present data, however, do not allow a definite localization of the phosphatidylglycerol pools.", "contents": "Recognition of different pools of phosphatidylglycerol in intact cells and isolated membranes of Acholeplasma laidlawii by phospholipase A2. Phospholipase A2 (EC 3.1.1.4) from pig pancreas hydrolyzes phosphatidylglycerol in intact cells and isolated membranes of Acholeplasma laidlawii. Complete degradation of phosphatidylglycerol in intact cells at 37 degrees C does not result in lysis as shown by the retention of intracellular K+ ions and the cytoplasmic glucose-6-phosphatase, as well as the inability to detect activity of membrane-bound intracellular NADH-oxidase. A. laidlawii was grown on linoleic acid. Phospholipase A2 treatment of these cells at 5 degrees C, at which temperature the lipids are still in the liquid-crystalline state, results in a rapid breakdown of 50% of the phosphatidylglycerol. The residual phosphatidylglycerol can be hydrolyzed only at elevated temperatures and at much smaller rates, depending strongly on the incubation temperature. When membranes isolated from these cells are incubated at 5 degrees C, 70% of the phosphatidylglycerol is hydrolyzed immediately. The hydrolysis of the residual 30% is again strongly temperature dependent. Cells were grown on palmitate, elaidate, or oleate to investigate possible effects of the lipid phase transition on the accessibility of phosphatidylglycerol for phospholipase A2. Under conditions in which all the lipid is in the solid state, no hydrolysis occurs. When solid and liquid-crystalline lipid phases coexist, a limited hydrolysis of phosphatidylglycerol can be observed. The results demonstrate the disposition of phosphatidylglycerol in three different pools in the membrane of A. laidlawii. Phospholipase A2 has been used to discriminate between these pools and to estimate the amount of phosphatidylglycerol which is present in the liquid-crystalline phase. The present data, however, do not allow a definite localization of the phosphatidylglycerol pools."}
{"id": "PMID:191066", "title": "31P nuclear magnetic resonance evidence for polyphosphoinositide associated with the hydrophobic segment of glycophorin A.", "content": "Glycophorin A, the major human erythrocyte sialoglycoprotein, contains a significant amount of phosphorus when isolated by the lithium diiodosalicylate-phenol procedure. Only a small percentage (approximately 1%) of this phosphorus is phosphoprotein. 31P nuclear magnetic resonance (NMR) analysis of glycophorin A has identified the remaining phosphorus content as phospholipid in origin. From the 31P chemical shifts, the phospholipid has been identified as diphosphoinositide. 31P NMR spectra of the peptides produced by trypsin hydrolysis of glycophorin A reveal that all the diphosphoinositide is closely associated with the hydrophobic region of the protein, suggesting that there is a specific affinity between this phospholipid and the intramembranous portion of glycophorin A.", "contents": "31P nuclear magnetic resonance evidence for polyphosphoinositide associated with the hydrophobic segment of glycophorin A. Glycophorin A, the major human erythrocyte sialoglycoprotein, contains a significant amount of phosphorus when isolated by the lithium diiodosalicylate-phenol procedure. Only a small percentage (approximately 1%) of this phosphorus is phosphoprotein. 31P nuclear magnetic resonance (NMR) analysis of glycophorin A has identified the remaining phosphorus content as phospholipid in origin. From the 31P chemical shifts, the phospholipid has been identified as diphosphoinositide. 31P NMR spectra of the peptides produced by trypsin hydrolysis of glycophorin A reveal that all the diphosphoinositide is closely associated with the hydrophobic region of the protein, suggesting that there is a specific affinity between this phospholipid and the intramembranous portion of glycophorin A."}
{"id": "PMID:191067", "title": "Electron spin resonance evidence for vertical asymmetry in animal cell membranes.", "content": "Two electron spin resonance (ESR) spin labels were used to monitor the physical state of bacterial and animal cell membranes: 5N10, a nitroxide derivative of decane, and 12NS-GA, a glucosamine derivative of 12-nitroxide stearic acid. Spectra were recorded at 1 degrees C intervals from approximately 5 to 45 degrees C. Arrhenius plots of log hH/hP vs. 1/K were obtained by measuring the amplitudes of the hydrocarbon and water signals, hH and hP, respectively. Two discontinuities in the Arrhenius plot (at characteristic temperatures t1 and th) were observed with bacterial cell membranes independent of the spin label employed. Analysis of sealed animal cell membrane samples revealed four characteristic temperatures when the hydrophobic spin lable 5N10 was used, but only two when the amphiphilic spin label 12NS-GA was used. The specific set of characteristic temperatures revealed with 12NS-GA depended on whether the membrane preparation was inside out (ISO) or right side out (RSO). Analysis of Newcastle disease virus, a source of RSO plasma membrane derived from host, revealed two characteristic temperatures at approximately 14 and 33 degrees C. Analysis of phagosomes, a source of ISO plasma membrane derived from LM cells, revealed two characteristic temperatures at approximately 23 and 38 degrees C. When unsealed or disrupted membrane preparations were spin labeled with 12NS-GA, both sets (RSO and ISO) of characteristic temperatures were revealed. The results indicate that the inner and outer monolayers of animal cell membranes are physically distinct and that the glycosylated spin label, 12NS-GA, is apparently restricted in its ability to flip across the membrane bilayer. In this study, characteristic temperatures were pinpointed by computer analysis of the ESR spectral data.", "contents": "Electron spin resonance evidence for vertical asymmetry in animal cell membranes. Two electron spin resonance (ESR) spin labels were used to monitor the physical state of bacterial and animal cell membranes: 5N10, a nitroxide derivative of decane, and 12NS-GA, a glucosamine derivative of 12-nitroxide stearic acid. Spectra were recorded at 1 degrees C intervals from approximately 5 to 45 degrees C. Arrhenius plots of log hH/hP vs. 1/K were obtained by measuring the amplitudes of the hydrocarbon and water signals, hH and hP, respectively. Two discontinuities in the Arrhenius plot (at characteristic temperatures t1 and th) were observed with bacterial cell membranes independent of the spin label employed. Analysis of sealed animal cell membrane samples revealed four characteristic temperatures when the hydrophobic spin lable 5N10 was used, but only two when the amphiphilic spin label 12NS-GA was used. The specific set of characteristic temperatures revealed with 12NS-GA depended on whether the membrane preparation was inside out (ISO) or right side out (RSO). Analysis of Newcastle disease virus, a source of RSO plasma membrane derived from host, revealed two characteristic temperatures at approximately 14 and 33 degrees C. Analysis of phagosomes, a source of ISO plasma membrane derived from LM cells, revealed two characteristic temperatures at approximately 23 and 38 degrees C. When unsealed or disrupted membrane preparations were spin labeled with 12NS-GA, both sets (RSO and ISO) of characteristic temperatures were revealed. The results indicate that the inner and outer monolayers of animal cell membranes are physically distinct and that the glycosylated spin label, 12NS-GA, is apparently restricted in its ability to flip across the membrane bilayer. In this study, characteristic temperatures were pinpointed by computer analysis of the ESR spectral data."}
{"id": "PMID:191068", "title": "A method for gene enrichment based on the avidin-biotin interaction. Application to the Drosophila ribosomal RNA genes.", "content": "A method of enriching, from the total DNA of an organism, for long DNA strands carrying a particular gene is described. The purified RNA corresponding to the gene is covalently attached to biotin via a cytochrome c bridge. This modified RNA is hybridized to the total DNA. Those DNA strands which hybridize are separated from all the other DNA, using the avidin-biotin interaction, by one of two methods. Avidin is covalently attached to submicroscopic polymer spheres; the complexes of avidin spheres with the DNA: RNA-biotin hybrids band in CsCl at a much lower buoyant density than does free DNA. Alternatively, the DNA:RNA-biotin hybrids are isolated by affinity chromatography on an avidin-solid support column. These methods have been used to prepare long single strands of Drosophila ribosomal DNA (rDNA) in high yield and 42 to 80% pure.", "contents": "A method for gene enrichment based on the avidin-biotin interaction. Application to the Drosophila ribosomal RNA genes. A method of enriching, from the total DNA of an organism, for long DNA strands carrying a particular gene is described. The purified RNA corresponding to the gene is covalently attached to biotin via a cytochrome c bridge. This modified RNA is hybridized to the total DNA. Those DNA strands which hybridize are separated from all the other DNA, using the avidin-biotin interaction, by one of two methods. Avidin is covalently attached to submicroscopic polymer spheres; the complexes of avidin spheres with the DNA: RNA-biotin hybrids band in CsCl at a much lower buoyant density than does free DNA. Alternatively, the DNA:RNA-biotin hybrids are isolated by affinity chromatography on an avidin-solid support column. These methods have been used to prepare long single strands of Drosophila ribosomal DNA (rDNA) in high yield and 42 to 80% pure."}
{"id": "PMID:191069", "title": "Primary structure of mouse, rat, and guinea pig cytochrome c.", "content": "For immunochemical and evolutionary reasons we determined the primary structure of cytochrome c from two strains of laboratory mice. Thioacetylthioethane and thioacetylthioglycolic acid were used in addition to conventional reagents for sequence determinations. The sequence was found to be identical with that of the rabbit except for residues 44 and 89 and consistent with the peptide compositional data reported by Hennig (Hennig, B. (1975), Eur. J. Biochem. 55, 167-183). The rat cytochrome c cymotryptic peptides were identical with those of the mouse in amino acid composition and amino-terminal residues. Further, peptide maps of cytochromes c of the guinea pig and two strains of rat indicate that all these animals have the same cytochrome c as the laboratory mouse. It is concluded that rodent cytochromes c are evolutionarily conservative and that there is no evidence for a generation-time effect in cytochrome c evolution.", "contents": "Primary structure of mouse, rat, and guinea pig cytochrome c. For immunochemical and evolutionary reasons we determined the primary structure of cytochrome c from two strains of laboratory mice. Thioacetylthioethane and thioacetylthioglycolic acid were used in addition to conventional reagents for sequence determinations. The sequence was found to be identical with that of the rabbit except for residues 44 and 89 and consistent with the peptide compositional data reported by Hennig (Hennig, B. (1975), Eur. J. Biochem. 55, 167-183). The rat cytochrome c cymotryptic peptides were identical with those of the mouse in amino acid composition and amino-terminal residues. Further, peptide maps of cytochromes c of the guinea pig and two strains of rat indicate that all these animals have the same cytochrome c as the laboratory mouse. It is concluded that rodent cytochromes c are evolutionarily conservative and that there is no evidence for a generation-time effect in cytochrome c evolution."}
{"id": "PMID:191070", "title": "Benzo[a]yrenedione/benzo[a]pyrenediol oxidation-reduction couples and the generation of reactive reduced molecular oxygen.", "content": "The ability of the isomeric quinone metabolites of benzo[a]pyrene, benzo[a]pyrene-6,12-dione, benzo[a]pyrene-1,6-dione, and benzo[a]pyrene-3,6-dione to undergo reversible, univalent oxidation-reduction cycles involving the corresponding benzo[a]pyrenediols and intermediate semiquinone radicals has been characterized. Under anaerobic conditions, all three benzo[a]pyrenediones are easily reduced to benzo[a]pyrenediols, even by mild biological agents such as NAD(P)H, cysteamine, and glutathione. The benzo[a]pyrenediols, in turn, are very rapidly autoxidized to the benzo[a]pyrenediones when exposed to air. Substantial amounts of hydrogen peroxide are produced during these autoxidations, and other reactive reduced oxygen species, such as the superoxide and hydroxyl radicals, are probably formed transiently as well. The benzo[a]pyrenediol-benzo[a]pyrenedione interconversions proceed by one-electron steps; the corresponsing semiquinone radicals can be monitored by electron spin resonance spectroscopy as inter mediates during these reactions carried out at high pH. Benzo[a]pyrenediones induce DNA strand scission when incubated with bacteriophage T7 DNA. This damage is modified by conditions which indicate that reduced oxygen species propagate the free-radical reactions responsible for the strand scission. Benzo[a]pyrenediones are electron-acceptor substrates for NADH dehydrogenase from Clostridium kluyveri. Catalytic amounds of these benzo[a]pyrene metabolites, together with this respiratory enzyme function as cyclic oxidation-reduction couples which link NADH and molecular oxygen in the continuous production of hydrogen peroxide. These data, together with preliminary results with cells in culture, indicate that benzo[a]pyrenediones are potentially harmful metabolites of benzo[a]pyrene, acting by processes which lead to their regeneration rather than depletion; nucleic acid and call damage is probably produced by the reactive reduced oxygen species resulting from such regenerative oxidation-reduction cycles.", "contents": "Benzo[a]yrenedione/benzo[a]pyrenediol oxidation-reduction couples and the generation of reactive reduced molecular oxygen. The ability of the isomeric quinone metabolites of benzo[a]pyrene, benzo[a]pyrene-6,12-dione, benzo[a]pyrene-1,6-dione, and benzo[a]pyrene-3,6-dione to undergo reversible, univalent oxidation-reduction cycles involving the corresponding benzo[a]pyrenediols and intermediate semiquinone radicals has been characterized. Under anaerobic conditions, all three benzo[a]pyrenediones are easily reduced to benzo[a]pyrenediols, even by mild biological agents such as NAD(P)H, cysteamine, and glutathione. The benzo[a]pyrenediols, in turn, are very rapidly autoxidized to the benzo[a]pyrenediones when exposed to air. Substantial amounts of hydrogen peroxide are produced during these autoxidations, and other reactive reduced oxygen species, such as the superoxide and hydroxyl radicals, are probably formed transiently as well. The benzo[a]pyrenediol-benzo[a]pyrenedione interconversions proceed by one-electron steps; the corresponsing semiquinone radicals can be monitored by electron spin resonance spectroscopy as inter mediates during these reactions carried out at high pH. Benzo[a]pyrenediones induce DNA strand scission when incubated with bacteriophage T7 DNA. This damage is modified by conditions which indicate that reduced oxygen species propagate the free-radical reactions responsible for the strand scission. Benzo[a]pyrenediones are electron-acceptor substrates for NADH dehydrogenase from Clostridium kluyveri. Catalytic amounds of these benzo[a]pyrene metabolites, together with this respiratory enzyme function as cyclic oxidation-reduction couples which link NADH and molecular oxygen in the continuous production of hydrogen peroxide. These data, together with preliminary results with cells in culture, indicate that benzo[a]pyrenediones are potentially harmful metabolites of benzo[a]pyrene, acting by processes which lead to their regeneration rather than depletion; nucleic acid and call damage is probably produced by the reactive reduced oxygen species resulting from such regenerative oxidation-reduction cycles."}
{"id": "PMID:191071", "title": "Separation of oligo(adenosine diphosphate ribose) fractions with various chain lengths and terminal structures.", "content": "Oligo(adenosine diphosphate ribose) preparations with chain lengths of 3 to 10 adenosine diphosphate ribose units were fractionated according to their chain lengths and their terminal structures by hydroxyapatite column chromatography and then polyacrylamide gel electrophoresis. The peak fractions from the hydroxyapatite column were each separated into two distinct subfractions by gel electrophoresis. The two subfractions were found to differ in chain length and terminal structure. A linear correlation was observed between the mobility and the logarithm of the chain length of oligo(adenosine diphosphate ribose) on gel electrophoresis, irrespective of the terminal structure.", "contents": "Separation of oligo(adenosine diphosphate ribose) fractions with various chain lengths and terminal structures. Oligo(adenosine diphosphate ribose) preparations with chain lengths of 3 to 10 adenosine diphosphate ribose units were fractionated according to their chain lengths and their terminal structures by hydroxyapatite column chromatography and then polyacrylamide gel electrophoresis. The peak fractions from the hydroxyapatite column were each separated into two distinct subfractions by gel electrophoresis. The two subfractions were found to differ in chain length and terminal structure. A linear correlation was observed between the mobility and the logarithm of the chain length of oligo(adenosine diphosphate ribose) on gel electrophoresis, irrespective of the terminal structure."}
{"id": "PMID:191072", "title": "Sedimentation of homogeneous double-strand DNA molecules.", "content": "Sedimentation velocity studies have been carried out with isolated double-strand DNA fragments prepared by digestion of PM2 phage with the restriction endonuclease Hae III. The results show that DNA molecules shorter than about 200 base pairs behave almost exactly as rigid rods with a diameter of 27 A. The behavior of the larger fragments (up to 1735 base pairs) can be described very well by either the theory of Yamakawa and Fujii (Yamakawa, H., and Fujii, M. (1973), Macromolecules 6. 407) using the same diameter and a persistence length of 575 A, or the theory of Hearst and Stockmayer (Hearst, J.E., and Stockmayer, W.H. (1962), J. Chem. Phys. 37, 1425) using a diameter of 20 A and a persistence length of 525 A.", "contents": "Sedimentation of homogeneous double-strand DNA molecules. Sedimentation velocity studies have been carried out with isolated double-strand DNA fragments prepared by digestion of PM2 phage with the restriction endonuclease Hae III. The results show that DNA molecules shorter than about 200 base pairs behave almost exactly as rigid rods with a diameter of 27 A. The behavior of the larger fragments (up to 1735 base pairs) can be described very well by either the theory of Yamakawa and Fujii (Yamakawa, H., and Fujii, M. (1973), Macromolecules 6. 407) using the same diameter and a persistence length of 575 A, or the theory of Hearst and Stockmayer (Hearst, J.E., and Stockmayer, W.H. (1962), J. Chem. Phys. 37, 1425) using a diameter of 20 A and a persistence length of 525 A."}
{"id": "PMID:191073", "title": "Novikoff hepatoma deoxyribonucleic acid polymerase. Identification of a stimulatory protein bound to the beta-polymerase.", "content": "The Novikoff hepatoma DNA polymerase-beta sediments as a 7.3S form in crude extracts but during purification sediments as a 4.1S form (after diethylaminoethyl-Sephadex chromatography) or as a 3.3S form (after DNA-cellulose chromatography). If 0.25 M ammonium sulfate or 0.5 M NaCl is included in the sucrose gradients, the 7.3S form sediments at 3.3 S; after removal of the salt, it sediments again at 7.3 S, indicating the reversibility of the aggregation phenomenon. By careful adjustment of ionic strength in the gradient, four distinct and reproducible forms of the enzyme sedimenting at 7.3, 5.8, 4.1, and 3.3 S can be generated. The isoelectric point of the DNA polymerase also changes during purification; the 7.3S form has a pI of 7.5, while the 4.1S form isoelectrically focuses at a pH of 8.5. During DNA-cellulose chromatography, the Novikoff beta-polymerase is separated from a stimulatory factor designated as Novikoff factor IV. Factor IV is a protein as shown by its sensitivity to protease and resistance to nucleases. It is responsible for converting the 3.3S enzyme to the 4.1S form since the 3.3S homogeneous DNA polymerase-beta sediments at 4.1 S in the presence of factor IV. Factor IV confers stability to the polymerase in low ionic strength buffers as well as stability to heat denaturation. Factor IV has the ability to increase the activity of the 3.3S homogeneous polymerase by about fourfold.", "contents": "Novikoff hepatoma deoxyribonucleic acid polymerase. Identification of a stimulatory protein bound to the beta-polymerase. The Novikoff hepatoma DNA polymerase-beta sediments as a 7.3S form in crude extracts but during purification sediments as a 4.1S form (after diethylaminoethyl-Sephadex chromatography) or as a 3.3S form (after DNA-cellulose chromatography). If 0.25 M ammonium sulfate or 0.5 M NaCl is included in the sucrose gradients, the 7.3S form sediments at 3.3 S; after removal of the salt, it sediments again at 7.3 S, indicating the reversibility of the aggregation phenomenon. By careful adjustment of ionic strength in the gradient, four distinct and reproducible forms of the enzyme sedimenting at 7.3, 5.8, 4.1, and 3.3 S can be generated. The isoelectric point of the DNA polymerase also changes during purification; the 7.3S form has a pI of 7.5, while the 4.1S form isoelectrically focuses at a pH of 8.5. During DNA-cellulose chromatography, the Novikoff beta-polymerase is separated from a stimulatory factor designated as Novikoff factor IV. Factor IV is a protein as shown by its sensitivity to protease and resistance to nucleases. It is responsible for converting the 3.3S enzyme to the 4.1S form since the 3.3S homogeneous DNA polymerase-beta sediments at 4.1 S in the presence of factor IV. Factor IV confers stability to the polymerase in low ionic strength buffers as well as stability to heat denaturation. Factor IV has the ability to increase the activity of the 3.3S homogeneous polymerase by about fourfold."}
{"id": "PMID:191074", "title": "Electron acceptors of photosynthetic bacterial reaction centers. Direct observation of oscillatory behaviour suggesting two closely equivalent ubiquinones.", "content": "When reaction centers are illuminated by a series of single turnover flashes ubisemiquinone is formed and destroyed on alternate flashes. This oscillatory behaviour can be observed with both optical and electron spin resonance techniques. The oscillations are dependent upon the presence of excess ubiquinone in a manner which suggests that two molecules may act almost equivalently as metastable primary acceptors forming a two-electron gate between the one-electron primary photoact and a two-electron secondary acceptor pool.", "contents": "Electron acceptors of photosynthetic bacterial reaction centers. Direct observation of oscillatory behaviour suggesting two closely equivalent ubiquinones. When reaction centers are illuminated by a series of single turnover flashes ubisemiquinone is formed and destroyed on alternate flashes. This oscillatory behaviour can be observed with both optical and electron spin resonance techniques. The oscillations are dependent upon the presence of excess ubiquinone in a manner which suggests that two molecules may act almost equivalently as metastable primary acceptors forming a two-electron gate between the one-electron primary photoact and a two-electron secondary acceptor pool."}
{"id": "PMID:191076", "title": "Acetylation and phosphorylation of Drosophila histones. Distribution of acetate and phosphate groups in fractionated chromatin.", "content": "The phosphorylation and acetylation patterns of Drosophila histones were studied after whole cell incubation with ortho [32P] phosphate or [3H] acetate. Radioactive phosphate associated mainly with H1, H3, and H4 and radioactive acetate was associated mainly with H3, H4, and H2B. H3 showed the highest specific activity of both labels. Two chromatin fractionation methods were employed to investigate the distribution of acetate and phosphate groups in histones form template-active and template-inactive regions. The levels of both acetate and phosphate groups were higher in histones from template-active regions.", "contents": "Acetylation and phosphorylation of Drosophila histones. Distribution of acetate and phosphate groups in fractionated chromatin. The phosphorylation and acetylation patterns of Drosophila histones were studied after whole cell incubation with ortho [32P] phosphate or [3H] acetate. Radioactive phosphate associated mainly with H1, H3, and H4 and radioactive acetate was associated mainly with H3, H4, and H2B. H3 showed the highest specific activity of both labels. Two chromatin fractionation methods were employed to investigate the distribution of acetate and phosphate groups in histones form template-active and template-inactive regions. The levels of both acetate and phosphate groups were higher in histones from template-active regions."}
{"id": "PMID:191077", "title": "Albumin synthesis in cultured hempatoma cells. Regulation by essential amino acids.", "content": "The effects of essential amino acids on albumin synthesis by a mouse hepatoma cell line have been investigated. The amino acids tested were tryptophan, phenylalanine, histidine, isoleucine and leucine. Cellular rates of synthesis (molecules albumin/cell per min) were determined from rates of [3H]leucine incorporation into immunoprecipitable albumin in the culture medium. The effects of amino acids on albumin synthesis fall into three distinct groups. The concentration of tryptophan producing half-maximal synthesis is 4 micronM. The corresponding concentration for leucine is 100 micronM. Histidine, phenylalanine and isoleucine were very similar, the half-maximal concentrations being approximately 15 micronM. The concentrations of amino acids producing half-maximal synthesis correlate directly with the amino acid composition of albumin. The levels of these essential amino acids necessary to saturate albumin synthesis have been compared with amino acid levels in normal plasma.", "contents": "Albumin synthesis in cultured hempatoma cells. Regulation by essential amino acids. The effects of essential amino acids on albumin synthesis by a mouse hepatoma cell line have been investigated. The amino acids tested were tryptophan, phenylalanine, histidine, isoleucine and leucine. Cellular rates of synthesis (molecules albumin/cell per min) were determined from rates of [3H]leucine incorporation into immunoprecipitable albumin in the culture medium. The effects of amino acids on albumin synthesis fall into three distinct groups. The concentration of tryptophan producing half-maximal synthesis is 4 micronM. The corresponding concentration for leucine is 100 micronM. Histidine, phenylalanine and isoleucine were very similar, the half-maximal concentrations being approximately 15 micronM. The concentrations of amino acids producing half-maximal synthesis correlate directly with the amino acid composition of albumin. The levels of these essential amino acids necessary to saturate albumin synthesis have been compared with amino acid levels in normal plasma."}
{"id": "PMID:191078", "title": "Inhibition of simian virus 40 DNA synthesis in Yaba virus-preinfected cells.", "content": "The effect of Yaba virus preinfection on DNA synthesis in SV40-infected Jinet cells was studied. Time-course synthesis studies were conducted using the incorporation of labeled thymidine. Yaba virus preinfection resulted in the inhibition of SV40 DNA synthesis when the elapsed time between Yaba virus and SV40 infections was three days. This inhibition was demonstrated by hybridization studies and sedimentation analysis. In addition, the usual stimulation of cellular DNA synthesis induced by SV40 infection was inhibited. This inhibition occurred at a time in Yaba virus infection when no cytoplasmic Yaba virus-specific DNA synthesis occurred.", "contents": "Inhibition of simian virus 40 DNA synthesis in Yaba virus-preinfected cells. The effect of Yaba virus preinfection on DNA synthesis in SV40-infected Jinet cells was studied. Time-course synthesis studies were conducted using the incorporation of labeled thymidine. Yaba virus preinfection resulted in the inhibition of SV40 DNA synthesis when the elapsed time between Yaba virus and SV40 infections was three days. This inhibition was demonstrated by hybridization studies and sedimentation analysis. In addition, the usual stimulation of cellular DNA synthesis induced by SV40 infection was inhibited. This inhibition occurred at a time in Yaba virus infection when no cytoplasmic Yaba virus-specific DNA synthesis occurred."}
{"id": "PMID:191079", "title": "The translation of globin messenger RNA with use of muscle initiation factors.", "content": "The ability of embryonic chicken muscle initiation factors to translate rabbit globin messenger RNA in an efficient, fractionated cell-free system has been examined. Although muscle factors stimulate leucine incorporation to only 15--35% the levels achieved with rabbit reticulocyte initiation factors, they synthesize more than one globin chain per mRNA molecule and both alpha and beta globin are produced. Increasing the ribosome concentration and adding the polyamine spermidine to the system produce stimulatory effects which are quantitatively and qualitatively similar for both factor preparations. The lower efficiency of synthesis of muscle factors relative to reticulocyte factors is also apparent when mRNA from encephalomyocarditis virus or embryonic chicken muscle polysomes are used in the cell-free system. These results do not support a specific restriction in the capacity of muscle factors to translate globin mRNA. Furthermore, the similarity of the effects of presumed non-specific components on the activity of muscle and reticulocyte factors suggests that globin synthesis in the cell-free system may be controlled in a similar fashion for both preparations.", "contents": "The translation of globin messenger RNA with use of muscle initiation factors. The ability of embryonic chicken muscle initiation factors to translate rabbit globin messenger RNA in an efficient, fractionated cell-free system has been examined. Although muscle factors stimulate leucine incorporation to only 15--35% the levels achieved with rabbit reticulocyte initiation factors, they synthesize more than one globin chain per mRNA molecule and both alpha and beta globin are produced. Increasing the ribosome concentration and adding the polyamine spermidine to the system produce stimulatory effects which are quantitatively and qualitatively similar for both factor preparations. The lower efficiency of synthesis of muscle factors relative to reticulocyte factors is also apparent when mRNA from encephalomyocarditis virus or embryonic chicken muscle polysomes are used in the cell-free system. These results do not support a specific restriction in the capacity of muscle factors to translate globin mRNA. Furthermore, the similarity of the effects of presumed non-specific components on the activity of muscle and reticulocyte factors suggests that globin synthesis in the cell-free system may be controlled in a similar fashion for both preparations."}
{"id": "PMID:191080", "title": "Organophosphate inhibitors. The stereospecificity of hydrolysis of methyl n-butyl p-nitrophenyl phosphate by serum phosphotriesterases (EC 3.1.1.2) and by acetylcholinesterases (EC 3.1.1.7).", "content": "A chiral phosphotriester, methyl n-butyl p-nitrophenyl phosphate was used to determine the stereospecificity of hydrolysis catalysed by serum phosphotriesterases (aryl-ester hydrolases, EC 3.1.1.2) from horse, ox and rabbit. Each enzyme hydrolysed the (-)-enantiomer more quickly. The same phosphate was used to inhibit acetycholinesterase (acetycholine hydrolase, EC 3.1.1.7) from ox, rabbit and electric eel, and in each case, the (+)-enantiomer caused more rapid inhibition. Serum phosphotriesterase did not catalyse the dephosphorylation of dialkyphosphoryl-acetylcholinesterase or dialkylphosphoryl-carboxylesterase. Levels of serum phosphotriesterase in rabbits which received sub-lethal injections of the phosphotriester remained unchanged after one or several injections. In the same rabbits, the levels of blood acetylcholinesterase fell sharply following injections, but normal values were regained in 2-8 days. Serum phosphotriesterases seem incapable either of preventing acute phosphotriester poisoning or of regenerating active enzyme from phosphorylated acetylcholinesterase. However, phosphotriesterases would act in cases of chronic exposure by catalysing the hydrolysis of such organophosphate poisons as remain in the blood.", "contents": "Organophosphate inhibitors. The stereospecificity of hydrolysis of methyl n-butyl p-nitrophenyl phosphate by serum phosphotriesterases (EC 3.1.1.2) and by acetylcholinesterases (EC 3.1.1.7). A chiral phosphotriester, methyl n-butyl p-nitrophenyl phosphate was used to determine the stereospecificity of hydrolysis catalysed by serum phosphotriesterases (aryl-ester hydrolases, EC 3.1.1.2) from horse, ox and rabbit. Each enzyme hydrolysed the (-)-enantiomer more quickly. The same phosphate was used to inhibit acetycholinesterase (acetycholine hydrolase, EC 3.1.1.7) from ox, rabbit and electric eel, and in each case, the (+)-enantiomer caused more rapid inhibition. Serum phosphotriesterase did not catalyse the dephosphorylation of dialkyphosphoryl-acetylcholinesterase or dialkylphosphoryl-carboxylesterase. Levels of serum phosphotriesterase in rabbits which received sub-lethal injections of the phosphotriester remained unchanged after one or several injections. In the same rabbits, the levels of blood acetylcholinesterase fell sharply following injections, but normal values were regained in 2-8 days. Serum phosphotriesterases seem incapable either of preventing acute phosphotriester poisoning or of regenerating active enzyme from phosphorylated acetylcholinesterase. However, phosphotriesterases would act in cases of chronic exposure by catalysing the hydrolysis of such organophosphate poisons as remain in the blood."}
{"id": "PMID:191081", "title": "Purification and properties of a phosphoprotein phosphatase from rat liver.", "content": "A phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) has been partially purified from rat liver homogenates by (NH4)2SO4 and ethanol precipitations followed by DEAE-cellulose and Sepharose 6B chromatography. The phosphoprotein phosphatase is capable of cleaving [32P]phosphate from radiolabelled phosphopyruvate kinase (type L) (EC 2.7.1.40), phosphohistones, and phosphoprotamine. However, it did not detectably dephosphorylate ATP, ADP, DL-phosphorylserine or beta-glycerophosphate. Dephosphorylation of [32P]phosphopyruvate kinase was stimulated by divalent cations and inhibited by ATP, ADP, Fru-1,6-P2, and orthophosphate. Divalene cations could reverse inhibition induced by ADP or ATP. At least one function of the phosphoprotein phosphatase may be to remove phosphate groups from the phosphorylated form of pyruvate kinase in the liver.", "contents": "Purification and properties of a phosphoprotein phosphatase from rat liver. A phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) has been partially purified from rat liver homogenates by (NH4)2SO4 and ethanol precipitations followed by DEAE-cellulose and Sepharose 6B chromatography. The phosphoprotein phosphatase is capable of cleaving [32P]phosphate from radiolabelled phosphopyruvate kinase (type L) (EC 2.7.1.40), phosphohistones, and phosphoprotamine. However, it did not detectably dephosphorylate ATP, ADP, DL-phosphorylserine or beta-glycerophosphate. Dephosphorylation of [32P]phosphopyruvate kinase was stimulated by divalent cations and inhibited by ATP, ADP, Fru-1,6-P2, and orthophosphate. Divalene cations could reverse inhibition induced by ADP or ATP. At least one function of the phosphoprotein phosphatase may be to remove phosphate groups from the phosphorylated form of pyruvate kinase in the liver."}
{"id": "PMID:191082", "title": "UDPglucose dehydrogenase. Kinetics and their mechanistic implications.", "content": "Initial velocity and product inhibition studies were carried out on UDP-glucose dehydrogenase (UDPglucose: NAD+ 6-oxidoreductase, EC 1.1.1.22) from beef liver to determine if the kinetics of the reaction are compatible with the established mechanism. An intersecting initial velocity pattern was observed with NAD+ as the variable substrate and UDPG as the changing fixed substrate. UDPglucuronic acid gave competitive inhibition of UDPG and non-competitive inhibition of NAD+. Inhibition by NADH gave complex patterns.Lineweaver-Burk plots of 1/upsilon versus 1/NAD+ at varied levels of NADH gave highly non-linear curves. At levels of NAD+ below 0.05 mM, non-competitive inhibition patterns were observed giving parabolic curves. Extrapolation to saturation with NAD+ showed NADH gave linear uncompetitive inhibition of UDPG if NAD+ was saturating. However, at levels of NAD+ above 0.10 mM, NADH became a competitive inhibitor of NAD+ (parabolic curves) and when NAD+ was saturating NADH gave no inhibition of UDPG. NADH was non-competitive versus UDPG when NAD+ was not saturating. These results are compatible with a mechanism in which UDPG binds first, followed by NAD+, which is reduced and released. A second mol of NAD+ is then bound, reduced, and released. The irreversible step in the reaction must occur after the release of the second mol of NADH but before the release of UDPglucuronic acid. This is apparently caused by the hydrolysis of a thiol ester between UDPglucoronic acid and the essential thiol group of the enzyme. Examination of rate equations indicated that this hydrolysis is the rate-limiting step in the overall reaction. The discontinuity in the velocities observed at high NAD+ concentrations is apparently caused by the binding of NAD+ in the active site after the release of the second mol of NADH, eliminating the NADH inhibition when NAD+ becomes saturating.", "contents": "UDPglucose dehydrogenase. Kinetics and their mechanistic implications. Initial velocity and product inhibition studies were carried out on UDP-glucose dehydrogenase (UDPglucose: NAD+ 6-oxidoreductase, EC 1.1.1.22) from beef liver to determine if the kinetics of the reaction are compatible with the established mechanism. An intersecting initial velocity pattern was observed with NAD+ as the variable substrate and UDPG as the changing fixed substrate. UDPglucuronic acid gave competitive inhibition of UDPG and non-competitive inhibition of NAD+. Inhibition by NADH gave complex patterns.Lineweaver-Burk plots of 1/upsilon versus 1/NAD+ at varied levels of NADH gave highly non-linear curves. At levels of NAD+ below 0.05 mM, non-competitive inhibition patterns were observed giving parabolic curves. Extrapolation to saturation with NAD+ showed NADH gave linear uncompetitive inhibition of UDPG if NAD+ was saturating. However, at levels of NAD+ above 0.10 mM, NADH became a competitive inhibitor of NAD+ (parabolic curves) and when NAD+ was saturating NADH gave no inhibition of UDPG. NADH was non-competitive versus UDPG when NAD+ was not saturating. These results are compatible with a mechanism in which UDPG binds first, followed by NAD+, which is reduced and released. A second mol of NAD+ is then bound, reduced, and released. The irreversible step in the reaction must occur after the release of the second mol of NADH but before the release of UDPglucuronic acid. This is apparently caused by the hydrolysis of a thiol ester between UDPglucoronic acid and the essential thiol group of the enzyme. Examination of rate equations indicated that this hydrolysis is the rate-limiting step in the overall reaction. The discontinuity in the velocities observed at high NAD+ concentrations is apparently caused by the binding of NAD+ in the active site after the release of the second mol of NADH, eliminating the NADH inhibition when NAD+ becomes saturating."}
{"id": "PMID:191083", "title": "Distinction between NAD- and NADH-binding forms of mitochondrial malate dehydrogenase as shown by inhibition with thenoyltrifuoroacetone.", "content": "The inhibition of mitochondrial malate dehydrogenase (L-malate : NADH oxidoreductase, EC 1.1.1.37) by 2-thenoyltrifluoroacetone (TTFA) was investigated at pH 8.0 where both forward and backward reactions can be measured. The inhibition with respect to malate is non-competitive at finite NAD concentrations. Increasing the NAD concentrations lowers the slope of the double reciprocal plot so that at infinite NAD the inhibition is uncompetitive. The inhibition with respect to oxaloacetate is non-competitive. Increasing the NADH concentration lowers the slope and intercept of the double reciprocal plot so that at infinite NADH the inhibition is nil. The inhibition with respect to NADH is competitive, whatever the oxaloacetate concentrations are. The inhibition with respect to NAD, at all malate concentrations, is non-competitive. This pattern of inhibition is incompatible with any model assuming that NAD and NADH reacts with identical forms of the enzyme. On the other hand the reciprocating compulsory ordered mechanism, where the two subunits of the dimeric enzyme are working in concert, can account for all the experimental results. It is concluded that NAD and NADH bind to different forms of the enzyme separated by reversible steps. Only one form (see text), the one which binds NADH, can react to form the dead end complex (see text). The similarity between mechanism of inhibition by thenoyltrifluoroacetone and other hydrophobic inhibitors of malate dehydrogenase is discussed.", "contents": "Distinction between NAD- and NADH-binding forms of mitochondrial malate dehydrogenase as shown by inhibition with thenoyltrifuoroacetone. The inhibition of mitochondrial malate dehydrogenase (L-malate : NADH oxidoreductase, EC 1.1.1.37) by 2-thenoyltrifluoroacetone (TTFA) was investigated at pH 8.0 where both forward and backward reactions can be measured. The inhibition with respect to malate is non-competitive at finite NAD concentrations. Increasing the NAD concentrations lowers the slope of the double reciprocal plot so that at infinite NAD the inhibition is uncompetitive. The inhibition with respect to oxaloacetate is non-competitive. Increasing the NADH concentration lowers the slope and intercept of the double reciprocal plot so that at infinite NADH the inhibition is nil. The inhibition with respect to NADH is competitive, whatever the oxaloacetate concentrations are. The inhibition with respect to NAD, at all malate concentrations, is non-competitive. This pattern of inhibition is incompatible with any model assuming that NAD and NADH reacts with identical forms of the enzyme. On the other hand the reciprocating compulsory ordered mechanism, where the two subunits of the dimeric enzyme are working in concert, can account for all the experimental results. It is concluded that NAD and NADH bind to different forms of the enzyme separated by reversible steps. Only one form (see text), the one which binds NADH, can react to form the dead end complex (see text). The similarity between mechanism of inhibition by thenoyltrifluoroacetone and other hydrophobic inhibitors of malate dehydrogenase is discussed."}
{"id": "PMID:191084", "title": "Regulation of glycogen synthetase and phosphorylase phosphatase activities in rat adipose tissue.", "content": "Incubation of a rat adipose tissue homogenate causes a time and temperature dependent activation of glycogen synthetase (UDP glucose:glycogen 4-alpha-glucosyltransferase) and simultaneous inactivation of phosphorylase (1,4-alpha-D-glucan: orthophosphate alpha-glucosyltransferase, EC 2.4.1.1). Activation of glycogen synthetase at 15 and 23 degrees C was preceded by a lag period. The duration of the lag period could not be correlated with significant changes in phosphorylase activity. Addition of glucose and methylxanthines caused an increase in the rates of glycogen synthetase activation and phosphorylase inactivation. The effect on glycogen synthetase activation was mainly on the linear phase. Addition of AMP inhibited phosphorylase inactivation and accelerated glycogen synthetase activation. Addition of muscle phosphorylase alpha caused a prolongation of the lag period which lasted until phosphorylase alpha activity had decreased to the level originally present in the preparation. It is concluded that in adipose tissue activation of glycogen synthetase is not dependent on prior inactivation of phosphorylase and that other factors should be looked for to explain the lag period preceding glycogen synthetase activation.", "contents": "Regulation of glycogen synthetase and phosphorylase phosphatase activities in rat adipose tissue. Incubation of a rat adipose tissue homogenate causes a time and temperature dependent activation of glycogen synthetase (UDP glucose:glycogen 4-alpha-glucosyltransferase) and simultaneous inactivation of phosphorylase (1,4-alpha-D-glucan: orthophosphate alpha-glucosyltransferase, EC 2.4.1.1). Activation of glycogen synthetase at 15 and 23 degrees C was preceded by a lag period. The duration of the lag period could not be correlated with significant changes in phosphorylase activity. Addition of glucose and methylxanthines caused an increase in the rates of glycogen synthetase activation and phosphorylase inactivation. The effect on glycogen synthetase activation was mainly on the linear phase. Addition of AMP inhibited phosphorylase inactivation and accelerated glycogen synthetase activation. Addition of muscle phosphorylase alpha caused a prolongation of the lag period which lasted until phosphorylase alpha activity had decreased to the level originally present in the preparation. It is concluded that in adipose tissue activation of glycogen synthetase is not dependent on prior inactivation of phosphorylase and that other factors should be looked for to explain the lag period preceding glycogen synthetase activation."}
{"id": "PMID:191085", "title": "The EPR of low spin heme complexes. Relation of the t2g hole model to the directional properties of the g tensor, and a new method for calculating the ligand field parameters.", "content": "A simple method is presented for calculating the parameters of the hole model for distorted octahedral, low spin (t2g)5 complexes. In the case of negligible covalent bonding explicit formulas for the coefficients of the Kramer's doublet, (formula: see text). The two numerically largest g values define the plane and orientation of the orbital with the largest coefficient, which in turn indicates the directions of maximal unpaired spin density. The energy of eta with respect to xi (in units of lambda, the spin-orbit coupling constant) is (formula: see text). The product gzgygx, independent of axes, and positive for free electrons, is shown to be positive for tetragonal and negative for nearly octahedral complexes. It is considered positive for hemes. In this method coefficients will only be normalized when there is no covalency. For the majority of published cases they are, to about 1%. Since this discrepancy is larger than can be caused by propagated errors, covalency must be the rule. For comparative purposes A and B, uncorrected for covalency, should still be useful. Examination of published complete g tensors for five hemes shows that the largest g value is nearly normal to the heme plane. If the g values are taken positive and labelled so that gz greater than gy greater than gx, then the proper tetragonal axis is roughly normal to plane of the ring in hemes, but not in chlorins.", "contents": "The EPR of low spin heme complexes. Relation of the t2g hole model to the directional properties of the g tensor, and a new method for calculating the ligand field parameters. A simple method is presented for calculating the parameters of the hole model for distorted octahedral, low spin (t2g)5 complexes. In the case of negligible covalent bonding explicit formulas for the coefficients of the Kramer's doublet, (formula: see text). The two numerically largest g values define the plane and orientation of the orbital with the largest coefficient, which in turn indicates the directions of maximal unpaired spin density. The energy of eta with respect to xi (in units of lambda, the spin-orbit coupling constant) is (formula: see text). The product gzgygx, independent of axes, and positive for free electrons, is shown to be positive for tetragonal and negative for nearly octahedral complexes. It is considered positive for hemes. In this method coefficients will only be normalized when there is no covalency. For the majority of published cases they are, to about 1%. Since this discrepancy is larger than can be caused by propagated errors, covalency must be the rule. For comparative purposes A and B, uncorrected for covalency, should still be useful. Examination of published complete g tensors for five hemes shows that the largest g value is nearly normal to the heme plane. If the g values are taken positive and labelled so that gz greater than gy greater than gx, then the proper tetragonal axis is roughly normal to plane of the ring in hemes, but not in chlorins."}
{"id": "PMID:191086", "title": "Quantitative determination of human apolipoprotein D by electroimmunoassay and radial immunodiffusion.", "content": "1. An electroimmunoassay and a radial immunodiffusion procedure are described for the quantitative determination of human serum apolipoprotein D. Purified apolipoprotein D and antisera to both lipoprotein D and apolipoprotein D were used to standardize the assays. The assays are applicable to measurement of apolipoprotein D in serum and density classes. The electroimmunoassay is more sensitive (50 ng apolipoprotein D quantitatively detectable), rapid (time required for completion of assay is 5 h) and precise (the within- and between-assay coefficients of variation are 4 and 7%, respectively) than radial immunodiffusion. However, comparable results were obtained by both methods (r = 0.85). 2. Serum apolipoprotein D levels of normal subjects and hyperlipoproteinemic phenotypes IIa, IIb, III, IV and V were in the same range (10 to 12 mg/dl). In contrast, patients with hyperchylomicronemia (type I) had decreased apolipoprotein D levels (5 mg/dl; P less than 0.001). The apolipoprotein D in serum of normolipidemic subjects was detectable in all density classes but measurable only in HDL2 (21%), HDL3 (43%) and VHDL (36%). 3. Rocket electrophoresis is also a valuable tool for assessing the structural relationships among apolipoproteins or their constituent polypeptides. Interaction between serum and a mixture of antibodies to A-I, A-II and apolipoprotein D resulted in the formation of separate lipoprotein A and lipoprotein D rockets indicating that apolipoprotein D is not a constituent polypeptide of apolipoprotein A. This observation confirms the existence of lipoproteins A and D as separate lipoprotein families.", "contents": "Quantitative determination of human apolipoprotein D by electroimmunoassay and radial immunodiffusion. 1. An electroimmunoassay and a radial immunodiffusion procedure are described for the quantitative determination of human serum apolipoprotein D. Purified apolipoprotein D and antisera to both lipoprotein D and apolipoprotein D were used to standardize the assays. The assays are applicable to measurement of apolipoprotein D in serum and density classes. The electroimmunoassay is more sensitive (50 ng apolipoprotein D quantitatively detectable), rapid (time required for completion of assay is 5 h) and precise (the within- and between-assay coefficients of variation are 4 and 7%, respectively) than radial immunodiffusion. However, comparable results were obtained by both methods (r = 0.85). 2. Serum apolipoprotein D levels of normal subjects and hyperlipoproteinemic phenotypes IIa, IIb, III, IV and V were in the same range (10 to 12 mg/dl). In contrast, patients with hyperchylomicronemia (type I) had decreased apolipoprotein D levels (5 mg/dl; P less than 0.001). The apolipoprotein D in serum of normolipidemic subjects was detectable in all density classes but measurable only in HDL2 (21%), HDL3 (43%) and VHDL (36%). 3. Rocket electrophoresis is also a valuable tool for assessing the structural relationships among apolipoproteins or their constituent polypeptides. Interaction between serum and a mixture of antibodies to A-I, A-II and apolipoprotein D resulted in the formation of separate lipoprotein A and lipoprotein D rockets indicating that apolipoprotein D is not a constituent polypeptide of apolipoprotein A. This observation confirms the existence of lipoproteins A and D as separate lipoprotein families."}
{"id": "PMID:191087", "title": "Low molecular weight angiotensin I converting enzyme from rat lung.", "content": "A low molecular weight angiotensin I converting enzyme (light angiotensin enzyme) was isolated from a homogenate of rat lung subjected to dialysis against sodium acetate at pH 4.8. This enzyme has a molecular weight of 84 000 on Sephadex G-200 and a molecular weight of 91 000 on SDS-poly-acrylamide gel as compared with a molecular weight of 139 000 for angiotensin I converting enzyme on SDS-polyacrylamide. Light angiotensin enzyme was activated by NaCl  and inhibited by EDTA, angiotensin II, and bradykinin potentiating factor nonapeptide. Light angiotensin enzyme cross-reacted with antibody prepared against angiotensin I converting enzyme and stained with periodic acid-Schiff reagent as a glycoprotein. The evidence suggests that light angiotensin enzyme is a fragment of the higher molecular weight enzyme.", "contents": "Low molecular weight angiotensin I converting enzyme from rat lung. A low molecular weight angiotensin I converting enzyme (light angiotensin enzyme) was isolated from a homogenate of rat lung subjected to dialysis against sodium acetate at pH 4.8. This enzyme has a molecular weight of 84 000 on Sephadex G-200 and a molecular weight of 91 000 on SDS-poly-acrylamide gel as compared with a molecular weight of 139 000 for angiotensin I converting enzyme on SDS-polyacrylamide. Light angiotensin enzyme was activated by NaCl  and inhibited by EDTA, angiotensin II, and bradykinin potentiating factor nonapeptide. Light angiotensin enzyme cross-reacted with antibody prepared against angiotensin I converting enzyme and stained with periodic acid-Schiff reagent as a glycoprotein. The evidence suggests that light angiotensin enzyme is a fragment of the higher molecular weight enzyme."}
{"id": "PMID:191088", "title": "Effect of cartilage proteoglycans on human collagenase activities.", "content": "No significant inhibition of purified rheumatoid synovial collagenase was found when this enzyme was assayed in the presence of porcine or human cartilage proteoglycans. Reaction mixtures containing up to twice the amount of proteoglycan compared to that of collagen, w/w, had little effect on collagen degradation as judged by the reconstituted [4C]collagen fibril assay and polyacrylamide gel electrophoresis. Proteoglycans were not degraded by the synovial collagenase preparation. Although the human collagenases derived from rheumatoid synoviam, gastric mucosa, skin and granulocytes showed some reduction in activity when exposed to aggregated proteoglycans at high concentrations, disaggregated proteoglycans had no inhibitory effect. It is concluded that cartilage proteoglycans do not directly inhibit human collagenases in vitro, but in vivo they may provide some physical barriers which might limit the accessibility of the enzyme to its collagen substrate.", "contents": "Effect of cartilage proteoglycans on human collagenase activities. No significant inhibition of purified rheumatoid synovial collagenase was found when this enzyme was assayed in the presence of porcine or human cartilage proteoglycans. Reaction mixtures containing up to twice the amount of proteoglycan compared to that of collagen, w/w, had little effect on collagen degradation as judged by the reconstituted [4C]collagen fibril assay and polyacrylamide gel electrophoresis. Proteoglycans were not degraded by the synovial collagenase preparation. Although the human collagenases derived from rheumatoid synoviam, gastric mucosa, skin and granulocytes showed some reduction in activity when exposed to aggregated proteoglycans at high concentrations, disaggregated proteoglycans had no inhibitory effect. It is concluded that cartilage proteoglycans do not directly inhibit human collagenases in vitro, but in vivo they may provide some physical barriers which might limit the accessibility of the enzyme to its collagen substrate."}
{"id": "PMID:191089", "title": "The effect of antibiotics on the electrical polarisability of aqueous suspensions of bacteria.", "content": "The orientation of washed Escherichia coli bacteria in suspension induced by applied a.c. electric fields has been monitored by observing the accompanying changes in the intensity of light scattered by the suspension. The data enable the anisotropy of electrical polarisability deltaalpha to be determined. Changes in deltaalpha due to the addition of various antibiotics to the suspension have been measured as a function of both the antibiotic concentration and the temperature of the suspension. The results are taken to indicate that there is an accumulation of the antibiotic molecules at the bacterial surface.", "contents": "The effect of antibiotics on the electrical polarisability of aqueous suspensions of bacteria. The orientation of washed Escherichia coli bacteria in suspension induced by applied a.c. electric fields has been monitored by observing the accompanying changes in the intensity of light scattered by the suspension. The data enable the anisotropy of electrical polarisability deltaalpha to be determined. Changes in deltaalpha due to the addition of various antibiotics to the suspension have been measured as a function of both the antibiotic concentration and the temperature of the suspension. The results are taken to indicate that there is an accumulation of the antibiotic molecules at the bacterial surface."}
{"id": "PMID:191090", "title": "Action of cyclic nucleotide analogues in Chinese hamster ovary cells.", "content": "Cyclic nucleotide analogues have been tested for their ability to cause the morphological conversion of Chinese hamster ovary cells in culture, as well as for effects on cyclic AMP-related enzymes. The ability of the analogues to inhibit the cyclic AMP phosphodiesterase activity and to activate the cyclic AMP-dependent protein kinase activity in cell extracts has been measured. Cell cultures were incubated with the analogues and the effects on morphology, intracellular level of cyclic AMP, and in vivo protein kinase activation were determined. All analogues which induced the morphological conversion also caused in vivo activation of the cyclic AMP-dependent protein kinase. Only N6,O2'-dibutyryl and N6-monobutyryl cyclic AMP caused on increase in intracellular cyclic AMP, presumabley through inhibition of the intracellular cyclic AMP phosphodiesterase activity. The increase in cyclic AMP appears to cause the protein kinase activation. However, analogues such a 8-bromo and 8-benzylthio cyclic AMP do not cause any change in intracellular cyclic AMP level and appear to activate the intracellular cyclic AMP-dependent protein kinase directly.", "contents": "Action of cyclic nucleotide analogues in Chinese hamster ovary cells. Cyclic nucleotide analogues have been tested for their ability to cause the morphological conversion of Chinese hamster ovary cells in culture, as well as for effects on cyclic AMP-related enzymes. The ability of the analogues to inhibit the cyclic AMP phosphodiesterase activity and to activate the cyclic AMP-dependent protein kinase activity in cell extracts has been measured. Cell cultures were incubated with the analogues and the effects on morphology, intracellular level of cyclic AMP, and in vivo protein kinase activation were determined. All analogues which induced the morphological conversion also caused in vivo activation of the cyclic AMP-dependent protein kinase. Only N6,O2'-dibutyryl and N6-monobutyryl cyclic AMP caused on increase in intracellular cyclic AMP, presumabley through inhibition of the intracellular cyclic AMP phosphodiesterase activity. The increase in cyclic AMP appears to cause the protein kinase activation. However, analogues such a 8-bromo and 8-benzylthio cyclic AMP do not cause any change in intracellular cyclic AMP level and appear to activate the intracellular cyclic AMP-dependent protein kinase directly."}
{"id": "PMID:191091", "title": "Release of the phosphodiesterase activator by cyclic AMP-dependent ATP:protein phosphotransferase from subcellular fractions of rat brain.", "content": "The subcellular distribution of the endogenous phosphodiesterase activator and its release from membranes by a cyclic AMP-dependent ATP:protein phosphotransferase was studied in fractions and subfractions of rat brain homogenate. These fractions were obtained by differential centrifugation and sucrose density gradient; their identity was ascertained by electron microscopy and specific enzyme markers. In the subcellular particulate fractions, the concentration of activator is highest in the microsomal fraction, followed by the mitochondrial and nuclear fractions. Gradient centrifugation of the main mitochondrial subfraction revealed that activator was concentrated in those fractions containing mainly synaptic membranes. Activator was releasted from membranes by a cyclic AMP-dependent phosphorylation of membrane protein. The release of activator occurred mainly from the mitochondrial subfractions containing synaptic membranes and synaptic vesicles. The data support the view that a release of activator from membranes may be important in normalizing the elevated concentration of cyclic AMP following persistent transsynaptic activation of adenylate cyclase.", "contents": "Release of the phosphodiesterase activator by cyclic AMP-dependent ATP:protein phosphotransferase from subcellular fractions of rat brain. The subcellular distribution of the endogenous phosphodiesterase activator and its release from membranes by a cyclic AMP-dependent ATP:protein phosphotransferase was studied in fractions and subfractions of rat brain homogenate. These fractions were obtained by differential centrifugation and sucrose density gradient; their identity was ascertained by electron microscopy and specific enzyme markers. In the subcellular particulate fractions, the concentration of activator is highest in the microsomal fraction, followed by the mitochondrial and nuclear fractions. Gradient centrifugation of the main mitochondrial subfraction revealed that activator was concentrated in those fractions containing mainly synaptic membranes. Activator was releasted from membranes by a cyclic AMP-dependent phosphorylation of membrane protein. The release of activator occurred mainly from the mitochondrial subfractions containing synaptic membranes and synaptic vesicles. The data support the view that a release of activator from membranes may be important in normalizing the elevated concentration of cyclic AMP following persistent transsynaptic activation of adenylate cyclase."}
{"id": "PMID:191093", "title": "[Coordinative paramagnetic enzyme centers during hormonal carcinogenesis and tumor regression under conditions of hormonal regulation].", "content": "The ESR method was employed to study the distribution of the coordinative paramegnetic centers on the energy chain of electron transport and on the detoxifying system during carcinogenesis caused by a disturbance of the normal hormonal balance in the organism and at the tumour regression stage achieved with estrogen - in tumours of the ovary, spleen, liver and adrenals. At various stages of the hormonal carcinogenesis and under hormonal control both quantitative and qualitative changes on the paramagnetic centers were found. The tumour growth on liver and adrenals lowers the level of the catalytic form of the cytochrome P-450 and of the non-heme iron complexes. In metastases of ovarian tumours the kinetics of the triplet signal development is registered. In the tumour and on the liver an antibate change of the intensities of the signal was observed with g-factors of 2,1 and 2,15. At the tumour tissues a shift of the g-factor of free radicals was found - from g=2.005 to g=2.000. When a complete regression of tumours occured under hormonal balance control, the characteristics of the ESR spectra on the liver and adrenals restores to their values on intact tissues.", "contents": "[Coordinative paramagnetic enzyme centers during hormonal carcinogenesis and tumor regression under conditions of hormonal regulation]. The ESR method was employed to study the distribution of the coordinative paramegnetic centers on the energy chain of electron transport and on the detoxifying system during carcinogenesis caused by a disturbance of the normal hormonal balance in the organism and at the tumour regression stage achieved with estrogen - in tumours of the ovary, spleen, liver and adrenals. At various stages of the hormonal carcinogenesis and under hormonal control both quantitative and qualitative changes on the paramagnetic centers were found. The tumour growth on liver and adrenals lowers the level of the catalytic form of the cytochrome P-450 and of the non-heme iron complexes. In metastases of ovarian tumours the kinetics of the triplet signal development is registered. In the tumour and on the liver an antibate change of the intensities of the signal was observed with g-factors of 2,1 and 2,15. At the tumour tissues a shift of the g-factor of free radicals was found - from g=2.005 to g=2.000. When a complete regression of tumours occured under hormonal balance control, the characteristics of the ESR spectra on the liver and adrenals restores to their values on intact tissues."}
{"id": "PMID:191092", "title": "[Yield of pigment cation-radicals in the reaction of quinone photooxidation of chlorophyll].", "content": "Photoinduced transfer of electrons in alkohol solutions of chlorophyll and its deuterated analog, deuterochlorophyll containing the quinoses: p-benzoquinone, chloranyl, duroquinone, 1,4-naftoquinone and ubiquinone (coenzyme Q6) is studied. It is shown that pigment cation-radical and quinone anion-radical are the primary products of photoreaction. A relationship between stationary concentrations of deuterochlorophyll and p-benzoquinone radicals and quinone concentration in solution is obtained. The reaction mechanism and causes of other authors' (G. Tollin et al.) failure in finding pigment cation-radicals which are formed in the reaction of the latter with quinoses are discussed. It is shown that optimal conditions for accumulating photoinduced cation-radicals of the pigment in pigment solutions of chlorophyll with quinones are lowered temperature, high viscosity of the solvent, low pH of the solution, careful purification of the quinone from hydroquinone admixture.", "contents": "[Yield of pigment cation-radicals in the reaction of quinone photooxidation of chlorophyll]. Photoinduced transfer of electrons in alkohol solutions of chlorophyll and its deuterated analog, deuterochlorophyll containing the quinoses: p-benzoquinone, chloranyl, duroquinone, 1,4-naftoquinone and ubiquinone (coenzyme Q6) is studied. It is shown that pigment cation-radical and quinone anion-radical are the primary products of photoreaction. A relationship between stationary concentrations of deuterochlorophyll and p-benzoquinone radicals and quinone concentration in solution is obtained. The reaction mechanism and causes of other authors' (G. Tollin et al.) failure in finding pigment cation-radicals which are formed in the reaction of the latter with quinoses are discussed. It is shown that optimal conditions for accumulating photoinduced cation-radicals of the pigment in pigment solutions of chlorophyll with quinones are lowered temperature, high viscosity of the solvent, low pH of the solution, careful purification of the quinone from hydroquinone admixture."}
{"id": "PMID:191094", "title": "[Paramagnetic properties of hepatic tissues and transplantable hepatomas].", "content": "Paramagnetic properties of frozen samples of normal, fetal and regenerating liver tissues and of a number transplantable hepatomas of different level of differentiation were studied. The results obtained indicate that ESR spectrum character and the concentration of paramagnetic centres in frozen samples of live tissues as well reflect the differentiation level, and the level of tissue functional activity. It is shown of hepatoma 22 taken as an example that tumour growth is accompanied with a change of the content of free radicals and some paramagnetic centres in the tumour and hosts liver. It can be considered as a manifestation of a biophysical shift which characterizes the tumour growth and includes the system effect of the tumour on the organism.", "contents": "[Paramagnetic properties of hepatic tissues and transplantable hepatomas]. Paramagnetic properties of frozen samples of normal, fetal and regenerating liver tissues and of a number transplantable hepatomas of different level of differentiation were studied. The results obtained indicate that ESR spectrum character and the concentration of paramagnetic centres in frozen samples of live tissues as well reflect the differentiation level, and the level of tissue functional activity. It is shown of hepatoma 22 taken as an example that tumour growth is accompanied with a change of the content of free radicals and some paramagnetic centres in the tumour and hosts liver. It can be considered as a manifestation of a biophysical shift which characterizes the tumour growth and includes the system effect of the tumour on the organism."}
{"id": "PMID:191100", "title": "[Correlation of membrane-bound and free ribosomes in normal rat liver, Zajdela hepatoma rat liver and ascite cells proper].", "content": "The content of membrane-bound ribosomes in normal rat liver cells is 3 times as high as compared to that of free ribosomes. (K=membrane-bound ribosome RNAs divided by free ribosome RNAs=3, the opposite effect being observed in case of ascites hepatoma cells. A considerable increase in the free ribosome fraction in the liver of hepatoma-bearing rats occurs by the sixth day due to a decrease in the content of hepatoma-bearing rats occurs by the sixth day due to a decrease in the content of membrane-bound ribosomes (K=0.6). Similar, but less-pronounced changes were observed in liver cells of control animals after 48-hour starvation  (K=0.9), simulating the condition occurring during the last days of tumour animals' life. Thus, changes in the rativ of membrane-bound to free ribosomes in liver during the ascites tumour growth are probably specifics and are not only due to anorexia in Zajdela hepatoma animals.", "contents": "[Correlation of membrane-bound and free ribosomes in normal rat liver, Zajdela hepatoma rat liver and ascite cells proper]. The content of membrane-bound ribosomes in normal rat liver cells is 3 times as high as compared to that of free ribosomes. (K=membrane-bound ribosome RNAs divided by free ribosome RNAs=3, the opposite effect being observed in case of ascites hepatoma cells. A considerable increase in the free ribosome fraction in the liver of hepatoma-bearing rats occurs by the sixth day due to a decrease in the content of hepatoma-bearing rats occurs by the sixth day due to a decrease in the content of membrane-bound ribosomes (K=0.6). Similar, but less-pronounced changes were observed in liver cells of control animals after 48-hour starvation  (K=0.9), simulating the condition occurring during the last days of tumour animals' life. Thus, changes in the rativ of membrane-bound to free ribosomes in liver during the ascites tumour growth are probably specifics and are not only due to anorexia in Zajdela hepatoma animals."}
{"id": "PMID:191101", "title": "[Analysis of macromolecule alkylation in tissues of intact and tumor carrying mice].", "content": "Alkylation DNA reparation kinetics and the disintegration of alkylated RNA, proteins and lipids in liver, spleen and brain of intact and 22A hepatomic mice after a injection of 1-14C-nitrosomethylurea at a therapeutic dose are studied. The tissue studied are different in their macromolecules and lipids alkylation, in DNA reparation and RNA, protein and lipid degradation rates. Possible correlation between the time of the occurrence of DNA damages and the frequency of tumour emergence in different tissues is discussed. It is found that normal cells eliminate more rapidly degraded RNA, protein and lipid molecules and more rapidly repair DNA damages as compared with 22A hepatoma cells. It is suggested to be due to more rapid macromolecule metabolism in normal cells which specifies a selective sensitivity of tumour cells to alkylating agents and nitrosoalkylureas. The time of the occurrence of damages induced with alkylating agents and nitrosomethylureas is supposed to be a critical parameter in processes resulting in the selective sensitivity of normal and tumour cells.", "contents": "[Analysis of macromolecule alkylation in tissues of intact and tumor carrying mice]. Alkylation DNA reparation kinetics and the disintegration of alkylated RNA, proteins and lipids in liver, spleen and brain of intact and 22A hepatomic mice after a injection of 1-14C-nitrosomethylurea at a therapeutic dose are studied. The tissue studied are different in their macromolecules and lipids alkylation, in DNA reparation and RNA, protein and lipid degradation rates. Possible correlation between the time of the occurrence of DNA damages and the frequency of tumour emergence in different tissues is discussed. It is found that normal cells eliminate more rapidly degraded RNA, protein and lipid molecules and more rapidly repair DNA damages as compared with 22A hepatoma cells. It is suggested to be due to more rapid macromolecule metabolism in normal cells which specifies a selective sensitivity of tumour cells to alkylating agents and nitrosoalkylureas. The time of the occurrence of damages induced with alkylating agents and nitrosomethylureas is supposed to be a critical parameter in processes resulting in the selective sensitivity of normal and tumour cells."}
{"id": "PMID:191102", "title": "[Changes of the phospholipid bilayer structure under the adsorption of ferricytochrome c on its surface].", "content": "Changes in the mobility of phospholipid molecules in liposomes membranes under adsorption ferricytochrome c on its surface were studied by means of NMR and EPR spectroscopy. It is found that the interaction of cytochrome molecules with vesicles causes the broadening of 1H-NMR signals of hydrophobic as well as polar groups in cardiolipin and phosphatidylcholine in the presence of lauric or phosphatidic acid. This broadening of 1H-NMR signals in hydrophobic groups may be caused by decrease in the rate of lateral diffusion of phospholipid molecules. The changes in the correlation time of hydrophobic spin-proub in liposomes containing phosphatydiloholine and cardiolipin with the increase of ferricytochrome c concentration were also observed. These changes suggest that the formation of protein-phospholipid clusters results in the impair of the regular structure of phospholipid bilayer.", "contents": "[Changes of the phospholipid bilayer structure under the adsorption of ferricytochrome c on its surface]. Changes in the mobility of phospholipid molecules in liposomes membranes under adsorption ferricytochrome c on its surface were studied by means of NMR and EPR spectroscopy. It is found that the interaction of cytochrome molecules with vesicles causes the broadening of 1H-NMR signals of hydrophobic as well as polar groups in cardiolipin and phosphatidylcholine in the presence of lauric or phosphatidic acid. This broadening of 1H-NMR signals in hydrophobic groups may be caused by decrease in the rate of lateral diffusion of phospholipid molecules. The changes in the correlation time of hydrophobic spin-proub in liposomes containing phosphatydiloholine and cardiolipin with the increase of ferricytochrome c concentration were also observed. These changes suggest that the formation of protein-phospholipid clusters results in the impair of the regular structure of phospholipid bilayer."}
{"id": "PMID:191103", "title": "[A mechanism of mononucleotide formation under endonuclease hydrolysis].", "content": "It has been shown under poly-A hydrolysis by endonuclease A236 in the presence of large amounts of E. coli phosphatase that the formation of mononucleotides requires the presence of terminal 5'-P in the substrate. Simultaneously, it has been found for endonuclease A236 and nuclease of Serratia marcescens that the products of exhaustive hydrolysis carried out in the presence of excess amounts of phosphatase contain an additional nucleoside residue as compared to the ordinary products of exhaustive hydrolysis, the number of phosphate groups being equal in both cases.", "contents": "[A mechanism of mononucleotide formation under endonuclease hydrolysis]. It has been shown under poly-A hydrolysis by endonuclease A236 in the presence of large amounts of E. coli phosphatase that the formation of mononucleotides requires the presence of terminal 5'-P in the substrate. Simultaneously, it has been found for endonuclease A236 and nuclease of Serratia marcescens that the products of exhaustive hydrolysis carried out in the presence of excess amounts of phosphatase contain an additional nucleoside residue as compared to the ordinary products of exhaustive hydrolysis, the number of phosphate groups being equal in both cases."}
{"id": "PMID:191099", "title": "[Study of the metabolic synapse. II. Comparison of the effects of cyclic 3',5'-AMP and 3',5'-GMP].", "content": "Intracellular microiontoforetic injections of cyclic 3',5'-AMP and cyclic 3',5'-GMP elicit different responses in the same neuron. Drugs were injected by current of 1--10 nA using 3-barrel micropipettes. Unlike cyclic 3',5'-AMP arising the depolarization of the neuron, cyclic 3',5'-GMP usually hyperpolarizes it. An inhibitor of phosphodiesterases, papaverine, increases and prolongates effects of cyclic 3',5'-AMP and cyclic 3',5'-GMP, but in latter case the action of this drug seems to be less.", "contents": "[Study of the metabolic synapse. II. Comparison of the effects of cyclic 3',5'-AMP and 3',5'-GMP]. Intracellular microiontoforetic injections of cyclic 3',5'-AMP and cyclic 3',5'-GMP elicit different responses in the same neuron. Drugs were injected by current of 1--10 nA using 3-barrel micropipettes. Unlike cyclic 3',5'-AMP arising the depolarization of the neuron, cyclic 3',5'-GMP usually hyperpolarizes it. An inhibitor of phosphodiesterases, papaverine, increases and prolongates effects of cyclic 3',5'-AMP and cyclic 3',5'-GMP, but in latter case the action of this drug seems to be less."}
{"id": "PMID:191104", "title": "[Biochemical characteristics determining the rates of tumour growth in the organism].", "content": "Experimental data suggest that contrary to the findings obtained for normal and regenerating liver of mouse, the greater part of hexokinase (HK) in transplantable hepatomas is firmly bound to mitochondrial membranes. It is shown that the ratio of the bound HK activity (HKbound) to that of total HK activity (HKtotal) diminishes with a hepatoma growth. Malignization of hepatocytes also leads to a sharp decrease in the cytochrome oxidase (CO) octivity. Though the data obtained are well-correlated with the Warburg hypothesis, there is no direct correlation between the malignancy of hepatomas evaluated by their growth rates, and the biochemical parameters of the tumours studied. On the basis of fundamental principles of Warburg's, it is proposed to evaluate energy metabolism of hepatomas by the activity and subcellular distribution patterns of HK as well as be the activity of CO, according to the expression: [(HKtotal)2//HKbound-CO+HKbound-CO]. It is demonstrated that there exists a certain linear dependence between the integral characteristics of hepatoma energetics and their growth rates.", "contents": "[Biochemical characteristics determining the rates of tumour growth in the organism]. Experimental data suggest that contrary to the findings obtained for normal and regenerating liver of mouse, the greater part of hexokinase (HK) in transplantable hepatomas is firmly bound to mitochondrial membranes. It is shown that the ratio of the bound HK activity (HKbound) to that of total HK activity (HKtotal) diminishes with a hepatoma growth. Malignization of hepatocytes also leads to a sharp decrease in the cytochrome oxidase (CO) octivity. Though the data obtained are well-correlated with the Warburg hypothesis, there is no direct correlation between the malignancy of hepatomas evaluated by their growth rates, and the biochemical parameters of the tumours studied. On the basis of fundamental principles of Warburg's, it is proposed to evaluate energy metabolism of hepatomas by the activity and subcellular distribution patterns of HK as well as be the activity of CO, according to the expression: [(HKtotal)2//HKbound-CO+HKbound-CO]. It is demonstrated that there exists a certain linear dependence between the integral characteristics of hepatoma energetics and their growth rates."}
{"id": "PMID:191105", "title": "[Quaternary structure and allosteric properties of thiamine pyrophosphokinase from rat liver].", "content": "Using electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate thiamine pyrophosphokinase (EC 2.7.6.2) was found to possess quaternary structure and consist of two polypeptide chains. It was shown that besides active centres, the oligomer has allosteric centres for binding of Mg2+ ions, since treatment by HgCl2 and heating of the enzyme lead to complete \"desensibilisation\". This results in a disappearance of the S-shaped curve of the dependence of reaction rate on Mg2+ concentration, the Hill coefficient coming down to 1. It is assumed that thiamine pyrophosphokinase belongs to the class dissociating regulatory enzymes.", "contents": "[Quaternary structure and allosteric properties of thiamine pyrophosphokinase from rat liver]. Using electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate thiamine pyrophosphokinase (EC 2.7.6.2) was found to possess quaternary structure and consist of two polypeptide chains. It was shown that besides active centres, the oligomer has allosteric centres for binding of Mg2+ ions, since treatment by HgCl2 and heating of the enzyme lead to complete \"desensibilisation\". This results in a disappearance of the S-shaped curve of the dependence of reaction rate on Mg2+ concentration, the Hill coefficient coming down to 1. It is assumed that thiamine pyrophosphokinase belongs to the class dissociating regulatory enzymes."}
{"id": "PMID:191106", "title": "[The activity of polynucleotide phosphorylase in polyribosomes of regenerating liver of adult rats, liver of newborn rats and in some reinoculated tumours].", "content": "Specific activity and level of polynucleotide phosphorylase (PNPase) in polyribosomes of regenerating liver of adult rats, liver of newborn rats and in malignant tumours of rat (sarcoma M-1 and hepatoma 27) were studied. 24 hours after partial hepatectomy the specific activity and level of PNPase in regenerating liver decreased 3--4 times in the fraction of polyribosomes, bound to the endoplasmic reticulum membranes, and remained at a constantly low level in the fraction of free polyribosomes. The PNPase activity also showed a sharp decrease in the fraction of membrane-bound polyribosomes from newborn rats liver and could not be detected either in free or in bound polyribosomes from sarcoma M-1 or hepatoma 27. The PNPase activity in the fraction of bound polyribosomes increased with a decrease in the rate of liver growth (regenerating liver and newborn rats liver), and reached the level normal for adult animals. Possible mechanisms of regulation of the PNPase activity in animal tissue were studied. It was found that a 2-fold administration of cyclic 3,5'-AMP to intact animals (5 mg per 100 g of body weight) with an interval of 8 hours, corresponding to the interval between two peaks of the increase in cyclic 3,5'-AMP concentration following partial hepatectomy, diminished the PNPase specific activity in polyribosomes by 30%. A factor, presumably of protein origin, which induced a release of PNPase from polyribosomes of normal rat liver but did not affect the activity of the liberated enzyme, was detected in the cell sap of sarcoma M-1 and hepatoma 27.", "contents": "[The activity of polynucleotide phosphorylase in polyribosomes of regenerating liver of adult rats, liver of newborn rats and in some reinoculated tumours]. Specific activity and level of polynucleotide phosphorylase (PNPase) in polyribosomes of regenerating liver of adult rats, liver of newborn rats and in malignant tumours of rat (sarcoma M-1 and hepatoma 27) were studied. 24 hours after partial hepatectomy the specific activity and level of PNPase in regenerating liver decreased 3--4 times in the fraction of polyribosomes, bound to the endoplasmic reticulum membranes, and remained at a constantly low level in the fraction of free polyribosomes. The PNPase activity also showed a sharp decrease in the fraction of membrane-bound polyribosomes from newborn rats liver and could not be detected either in free or in bound polyribosomes from sarcoma M-1 or hepatoma 27. The PNPase activity in the fraction of bound polyribosomes increased with a decrease in the rate of liver growth (regenerating liver and newborn rats liver), and reached the level normal for adult animals. Possible mechanisms of regulation of the PNPase activity in animal tissue were studied. It was found that a 2-fold administration of cyclic 3,5'-AMP to intact animals (5 mg per 100 g of body weight) with an interval of 8 hours, corresponding to the interval between two peaks of the increase in cyclic 3,5'-AMP concentration following partial hepatectomy, diminished the PNPase specific activity in polyribosomes by 30%. A factor, presumably of protein origin, which induced a release of PNPase from polyribosomes of normal rat liver but did not affect the activity of the liberated enzyme, was detected in the cell sap of sarcoma M-1 and hepatoma 27."}
{"id": "PMID:191107", "title": "[Free-radicals formation in reductions of flavin. Study on the reduction of aminoethylcellulose-bound flavin].", "content": "The reduction of flavin by reduced diphosphopyridine nucleotide and photoreduction were studied spectrophotometrically. Flavin was covalently bound to aminoethylcellulose, therefore the interaction between flavin molecules was excluded. Nevertheless a considerable quantity of free radicals was demonstrated under these conditions. The experimental dependence of the radical concentration as a function of reduction degree is readily explained if the reduction of flavin proceeds in two consecutive one-electron steps. The ratio of the rate constants of both reactions for the reduction of flavin by NADH k2'/k1' was equal to 4, for the photoreductions k2'/k1' to 6.5.", "contents": "[Free-radicals formation in reductions of flavin. Study on the reduction of aminoethylcellulose-bound flavin]. The reduction of flavin by reduced diphosphopyridine nucleotide and photoreduction were studied spectrophotometrically. Flavin was covalently bound to aminoethylcellulose, therefore the interaction between flavin molecules was excluded. Nevertheless a considerable quantity of free radicals was demonstrated under these conditions. The experimental dependence of the radical concentration as a function of reduction degree is readily explained if the reduction of flavin proceeds in two consecutive one-electron steps. The ratio of the rate constants of both reactions for the reduction of flavin by NADH k2'/k1' was equal to 4, for the photoreductions k2'/k1' to 6.5."}
{"id": "PMID:191108", "title": "[Inhibition of pyridoxal kinase by 2- and 6-alkyl substituted vitamin B6 analogues and by pyridoxal oximes].", "content": "It is shown in the system with partially purified pyridoxal kinase from mouse liver, that the presence of one alkyl group in the 2nd or 6th positions of pyridine cycle in pyridoxole and pyridoxamine derivatives and pyridoxal oximes is a necessary condition which determines relatively high affinity of structural vitamin B6 analogues to the enzyme. 2'-n-Propylpyridoxal was phosphorylated by pyridoxal kinase with a relatively high rate, while 2-nor-6-methylpyridoxal, having a similar affinity to pyridoxal kinase, was not phosphorylated at all. The data obtained indicate an important role of the methyl group in the 2nd position of pyridine cycle in vitamin B6 molecule for its fixation in the enzyme active site and for the proper orientation, which provides enzymatic substrate phosphorylation. Some structural peculiarities of vitamin B6 analogues are considered, pre-determining their low or high efficiency as vitamin B6 antimetabolite in vivo.", "contents": "[Inhibition of pyridoxal kinase by 2- and 6-alkyl substituted vitamin B6 analogues and by pyridoxal oximes]. It is shown in the system with partially purified pyridoxal kinase from mouse liver, that the presence of one alkyl group in the 2nd or 6th positions of pyridine cycle in pyridoxole and pyridoxamine derivatives and pyridoxal oximes is a necessary condition which determines relatively high affinity of structural vitamin B6 analogues to the enzyme. 2'-n-Propylpyridoxal was phosphorylated by pyridoxal kinase with a relatively high rate, while 2-nor-6-methylpyridoxal, having a similar affinity to pyridoxal kinase, was not phosphorylated at all. The data obtained indicate an important role of the methyl group in the 2nd position of pyridine cycle in vitamin B6 molecule for its fixation in the enzyme active site and for the proper orientation, which provides enzymatic substrate phosphorylation. Some structural peculiarities of vitamin B6 analogues are considered, pre-determining their low or high efficiency as vitamin B6 antimetabolite in vivo."}
{"id": "PMID:191110", "title": "Metabolic rate and O2 consumption in newborns during different states of vigilance.", "content": "In 135 asymptomatic newborn infants, 1--53 days of age, body weight 1,820--4,120 g, indirect calometry was performed. According to the state of wakefulness the infants showed during the testing procedure, they were divided into four groups of vigilance (V1--V4). Metabolic rate and oxygen consumption showed similar results between groups V1, V2 and V3 (deep sleep; REM sleep; wakefulness with no muscular activity). V4 infants (with muscular activity) had a higher metabolic rate and O2 consumption. Correlation between  metabolic rate and body surface area is similar in V2 and V3 but shows a steeper slope in the V1 group. It is speculated that central regulatory mechanisms may account for this difference.", "contents": "Metabolic rate and O2 consumption in newborns during different states of vigilance. In 135 asymptomatic newborn infants, 1--53 days of age, body weight 1,820--4,120 g, indirect calometry was performed. According to the state of wakefulness the infants showed during the testing procedure, they were divided into four groups of vigilance (V1--V4). Metabolic rate and oxygen consumption showed similar results between groups V1, V2 and V3 (deep sleep; REM sleep; wakefulness with no muscular activity). V4 infants (with muscular activity) had a higher metabolic rate and O2 consumption. Correlation between  metabolic rate and body surface area is similar in V2 and V3 but shows a steeper slope in the V1 group. It is speculated that central regulatory mechanisms may account for this difference."}
{"id": "PMID:191115", "title": "Genetic influence in murine viral leukemogenesis.", "content": "Studies carried out over the past four decades on factors controlling the susceptibility to viral leukemias in mice have shown the existence of specific controlling gene loci. Evidence from a number of studies using various mouse strains and different leukemia viruses has shown that the controlling genes may act either directly or indirectly. \"In vitro\" experiments have shown controlling effects directed by the prospective target cells themselves in which effective virus infection and/or and/or replication is inhibitied. From \"in vivo\" experiments it is also evident that susceptibility may be controlled through indirect means mediated by immune relationships and other factors involved in the basic regulations of hematopoiesis. The present paper presents a brief review of the various genes known to control susceptibility and resistance to murine leukemia viruses. Certain conflicts in the literature relating to the naming of particular specific genes by different laboratories is also discussed, and some minor revisions in nomenclature designed to resolve some of the existing confusion are proposed.", "contents": "Genetic influence in murine viral leukemogenesis. Studies carried out over the past four decades on factors controlling the susceptibility to viral leukemias in mice have shown the existence of specific controlling gene loci. Evidence from a number of studies using various mouse strains and different leukemia viruses has shown that the controlling genes may act either directly or indirectly. \"In vitro\" experiments have shown controlling effects directed by the prospective target cells themselves in which effective virus infection and/or and/or replication is inhibitied. From \"in vivo\" experiments it is also evident that susceptibility may be controlled through indirect means mediated by immune relationships and other factors involved in the basic regulations of hematopoiesis. The present paper presents a brief review of the various genes known to control susceptibility and resistance to murine leukemia viruses. Certain conflicts in the literature relating to the naming of particular specific genes by different laboratories is also discussed, and some minor revisions in nomenclature designed to resolve some of the existing confusion are proposed."}
{"id": "PMID:191116", "title": "Antibody like activities against cholesterol ester in anti-LDL antiserum. An observation on the surface of LDL.", "content": "The antibody like activities against cholesterol and cholesterol ester were examined by means of radioimmunoassay system, immunolysis of liposomes containing cholesterol and other steroids. In comparison with anti-etiocholenic acid antiserum and anti-cholesterol succinate antiserum, it was proved that anti-LDL antiserum contained 2 kinds of antibodies, one was specific to the structure of cholesterol skeleton and other was specific to the whole structure of cholesterol ester. LDL only combined with anti-cholesterol succinate antibody resulting with the inhibition of the interaction between sheep red cell sensitized by cholesterol succinate and anti-cholesterol succinate antiserum by means of passive hemagglutionation reaction.", "contents": "Antibody like activities against cholesterol ester in anti-LDL antiserum. An observation on the surface of LDL. The antibody like activities against cholesterol and cholesterol ester were examined by means of radioimmunoassay system, immunolysis of liposomes containing cholesterol and other steroids. In comparison with anti-etiocholenic acid antiserum and anti-cholesterol succinate antiserum, it was proved that anti-LDL antiserum contained 2 kinds of antibodies, one was specific to the structure of cholesterol skeleton and other was specific to the whole structure of cholesterol ester. LDL only combined with anti-cholesterol succinate antibody resulting with the inhibition of the interaction between sheep red cell sensitized by cholesterol succinate and anti-cholesterol succinate antiserum by means of passive hemagglutionation reaction."}
{"id": "PMID:191117", "title": "Isoproterenol induced pancreatic secretion in rats. A comparison with secretin.", "content": "The stimulatory effects of isoproterenol and secretin on external pancreatic secretion were compared in the rat. 1. In acute fistula, pylorus ligation, atropine, glucagon did not change either of the stimulated secretions. Propranolol inhibited isoproterenol-induced secretion and did not change secretin induced stimulation. Theophylline alone displayed a large hydrelatic stimulatory effect, without increasing protein excretion; the effect of theophylline was additive with the effects of isoproterenol or secretin but no evidence was found of potentiation or prolongation of action. Isoproterenol did not increase pancreatic blood flow and induced no variations in the plasma levels of immunoreactive secretin. Combining various doses of isoproterenol and secretin did not allow to reach secretory levels greater than the maximal response to secretin. 2. In conscious rats chronic fistulae, isoproterenol and secretin had a distinct effect.", "contents": "Isoproterenol induced pancreatic secretion in rats. A comparison with secretin. The stimulatory effects of isoproterenol and secretin on external pancreatic secretion were compared in the rat. 1. In acute fistula, pylorus ligation, atropine, glucagon did not change either of the stimulated secretions. Propranolol inhibited isoproterenol-induced secretion and did not change secretin induced stimulation. Theophylline alone displayed a large hydrelatic stimulatory effect, without increasing protein excretion; the effect of theophylline was additive with the effects of isoproterenol or secretin but no evidence was found of potentiation or prolongation of action. Isoproterenol did not increase pancreatic blood flow and induced no variations in the plasma levels of immunoreactive secretin. Combining various doses of isoproterenol and secretin did not allow to reach secretory levels greater than the maximal response to secretin. 2. In conscious rats chronic fistulae, isoproterenol and secretin had a distinct effect."}
{"id": "PMID:191118", "title": "Inositol-less death in yeast results in a simultaneous increase in intracellular viscosity.", "content": "Inositol auxotrophs of yeast developing on isositol-deficient medium continue protein synthesis for 4-6 h, lose viability rapidly after 6 h, and show an increase in cytoplasmic viscosity as measured by spin label rotational motion. Cycloheximide prevents the rapid loss of cell viability, stops protein synthesis, and simultaneously prevents an increase in cytoplasmic viscosity. From these observations, we infer that intracellular translational diffusion is upset as a consequence of inositol starvation. Cell death may be caused by a modified intracellular diffusion environment.", "contents": "Inositol-less death in yeast results in a simultaneous increase in intracellular viscosity. Inositol auxotrophs of yeast developing on isositol-deficient medium continue protein synthesis for 4-6 h, lose viability rapidly after 6 h, and show an increase in cytoplasmic viscosity as measured by spin label rotational motion. Cycloheximide prevents the rapid loss of cell viability, stops protein synthesis, and simultaneously prevents an increase in cytoplasmic viscosity. From these observations, we infer that intracellular translational diffusion is upset as a consequence of inositol starvation. Cell death may be caused by a modified intracellular diffusion environment."}
{"id": "PMID:191120", "title": "[Quantitative assessment of the viability of renal tissue when the donor's body is treated differently].", "content": "It was shown that the vital capacity of the mouse kidney tissues quantitatively estimated by the in vitro growth in a plasma-free medium depended upon the condition of the donor organism. Depression of the culture growth was noted after the general X-irradiation of the animals, as well as following prolonged starvation and chloric cadmium poisoning. An increased growth of the kidney tissues was observed both in compensatory hypertrophy caused by unilateral nephrectomy and in subcutaneous inflammation.", "contents": "[Quantitative assessment of the viability of renal tissue when the donor's body is treated differently]. It was shown that the vital capacity of the mouse kidney tissues quantitatively estimated by the in vitro growth in a plasma-free medium depended upon the condition of the donor organism. Depression of the culture growth was noted after the general X-irradiation of the animals, as well as following prolonged starvation and chloric cadmium poisoning. An increased growth of the kidney tissues was observed both in compensatory hypertrophy caused by unilateral nephrectomy and in subcutaneous inflammation."}
{"id": "PMID:191121", "title": "Ultrastructural cytochemical analysis of blastic transformation of chronic myelocytic leukemia.", "content": "Ultrastructural cytochemical changes occurring during the blast phase of chronic myelocytic leukemia (CML) are described. Normal developing promyelocytes contain myeloperoxidase (MPO) -positive rough endoplasmic reticulum, nuclear envelope, and Golgi apparatus. All secretory granules of normal promyelocytes are also MPO-positive. In this study we have found abnormal promyelocytes with MPO-positive as well as MPO-negative secretory granules in blast phase CML patients which contrast with the normal pattern of MPO distribution in most CML patients not in the blast phase or in nonleukemic controls. Alkaline phosphatase activity was found in the nuclear envelope of blasts and promyelocytes of one of the blast transformation patients who had a markedly increased leukocyte alkaline phosphatase score. The cytochemical changes in the distribution of MPO suggest that immature leukemic cells may alter their patterns of secretory granule production. Such processes may reflect the emergence of an abnormal clone of cells during the blastic transformation of CML.", "contents": "Ultrastructural cytochemical analysis of blastic transformation of chronic myelocytic leukemia. Ultrastructural cytochemical changes occurring during the blast phase of chronic myelocytic leukemia (CML) are described. Normal developing promyelocytes contain myeloperoxidase (MPO) -positive rough endoplasmic reticulum, nuclear envelope, and Golgi apparatus. All secretory granules of normal promyelocytes are also MPO-positive. In this study we have found abnormal promyelocytes with MPO-positive as well as MPO-negative secretory granules in blast phase CML patients which contrast with the normal pattern of MPO distribution in most CML patients not in the blast phase or in nonleukemic controls. Alkaline phosphatase activity was found in the nuclear envelope of blasts and promyelocytes of one of the blast transformation patients who had a markedly increased leukocyte alkaline phosphatase score. The cytochemical changes in the distribution of MPO suggest that immature leukemic cells may alter their patterns of secretory granule production. Such processes may reflect the emergence of an abnormal clone of cells during the blastic transformation of CML."}
{"id": "PMID:191122", "title": "cGMP stimulation of stem cell proliferation.", "content": "The process by which resting hemopoietic stem cells become activated is poorly understood, but it has been suggested that cyclic nucleotide levels in the cell may play an important role. In the present study, the effect of various, nucleotides and stimulators of nucleotide synthesis upon the formation of in vitro granulocyte colonies has been examined. It was found that physiologic concentrations of 3', 5'-cyclic guanosine monophosphate enhanced the formation of granulocyte-macrophage colonies in the presence of colony-stimulating activity. The cells sensitive to cGMP activation were resistant to thymidine suicide and could not be activated by colony-stimulating activity alone. Therefore it was suggested that the cGMP sensitive stem cell was an ordinarily resting stem cell which was triggered into a proliferative state by cGMP.", "contents": "cGMP stimulation of stem cell proliferation. The process by which resting hemopoietic stem cells become activated is poorly understood, but it has been suggested that cyclic nucleotide levels in the cell may play an important role. In the present study, the effect of various, nucleotides and stimulators of nucleotide synthesis upon the formation of in vitro granulocyte colonies has been examined. It was found that physiologic concentrations of 3', 5'-cyclic guanosine monophosphate enhanced the formation of granulocyte-macrophage colonies in the presence of colony-stimulating activity. The cells sensitive to cGMP activation were resistant to thymidine suicide and could not be activated by colony-stimulating activity alone. Therefore it was suggested that the cGMP sensitive stem cell was an ordinarily resting stem cell which was triggered into a proliferative state by cGMP."}
{"id": "PMID:191123", "title": "Establishment of peripheral lymphoid cell cultures from patients with Hodgkin's disease depending on Epstein-Barr-Virus-reactivity and cellular immunity.", "content": "Peripheral blood lymphocytes from 43 patients with Hodgkin's disease were studied for spontaneous growth in longterm cultures in vitro. The rate of culture establishment in Hodgkin's patients was dependant on a positive Epstein-Barr-Virus (EBV)-seroreactivity and intact delayed hypersensitivity reaction to tuberculin. Localized and inactive disease, as well as the absence of atypical mononuclear cells in the peripheral blood had a favourable influence on the longterm in vitro growth. The overall establishment rate in Hodgkin patients was 18 out of 60 attempts (30%), 16 out of 34 (47%) in patients without treatment, only 2 out of 26 (7.7%) attempts during treatment. These results were compared with culture attempts of peripheral blood cells from healthy individuals and umbilical cord blood lymphocytes. Only 12 out of 60 attempts in healthy donors (18.2%) and 0 out of 49 attempts with umbilical cord blood lymphocytes were successful.", "contents": "Establishment of peripheral lymphoid cell cultures from patients with Hodgkin's disease depending on Epstein-Barr-Virus-reactivity and cellular immunity. Peripheral blood lymphocytes from 43 patients with Hodgkin's disease were studied for spontaneous growth in longterm cultures in vitro. The rate of culture establishment in Hodgkin's patients was dependant on a positive Epstein-Barr-Virus (EBV)-seroreactivity and intact delayed hypersensitivity reaction to tuberculin. Localized and inactive disease, as well as the absence of atypical mononuclear cells in the peripheral blood had a favourable influence on the longterm in vitro growth. The overall establishment rate in Hodgkin patients was 18 out of 60 attempts (30%), 16 out of 34 (47%) in patients without treatment, only 2 out of 26 (7.7%) attempts during treatment. These results were compared with culture attempts of peripheral blood cells from healthy individuals and umbilical cord blood lymphocytes. Only 12 out of 60 attempts in healthy donors (18.2%) and 0 out of 49 attempts with umbilical cord blood lymphocytes were successful."}
{"id": "PMID:191127", "title": "Inhibition by glucocorticoids of prostaglandin release from adipose tissue in vitro.", "content": "1 When rabbit chopped adipose tissue was incubated with a lipolytic agent (adrenocorticotrophic hormone, ACTH1-24, 0.1 microng/ml) in Krebs solution, prostaglandin E2 was formed in the tissue and about the same amount was found in the medium. 2 In the presence of indomethacin (1 microng/ml) the appearance of prostaglandin E2 was almost abolished both in the tissue and in the medium. 3 When the incubation was carried out in the presence of hydrocortisone or betamethasone (1-10 microng)ml) the concentration of prostaglandin E2 leaking or carried into the medium was significantly reduced, whereas that remaining in the tissue was significantly increased. This action of the steroids was not reversed by increasing substrate (arachidonic acid) concentration in the medium. 4 The steroids did not affect lipolysis, nor did they influence prostaglandin metabolism since such activity was not detectable in the adipose tissue. 5 Anti-inflammatory steroids therefore did not reduce prostaglandin formation but increased the tissue/medium ratio, which supports the view that they inhibit the release of prostaglandins after these have been synthesized.", "contents": "Inhibition by glucocorticoids of prostaglandin release from adipose tissue in vitro. 1 When rabbit chopped adipose tissue was incubated with a lipolytic agent (adrenocorticotrophic hormone, ACTH1-24, 0.1 microng/ml) in Krebs solution, prostaglandin E2 was formed in the tissue and about the same amount was found in the medium. 2 In the presence of indomethacin (1 microng/ml) the appearance of prostaglandin E2 was almost abolished both in the tissue and in the medium. 3 When the incubation was carried out in the presence of hydrocortisone or betamethasone (1-10 microng)ml) the concentration of prostaglandin E2 leaking or carried into the medium was significantly reduced, whereas that remaining in the tissue was significantly increased. This action of the steroids was not reversed by increasing substrate (arachidonic acid) concentration in the medium. 4 The steroids did not affect lipolysis, nor did they influence prostaglandin metabolism since such activity was not detectable in the adipose tissue. 5 Anti-inflammatory steroids therefore did not reduce prostaglandin formation but increased the tissue/medium ratio, which supports the view that they inhibit the release of prostaglandins after these have been synthesized."}
{"id": "PMID:191142", "title": "Subcellular distribution of cytochrome c oxidase, monoamine oxidase and lactate dehydrogenase in the developing chick telencephalon.", "content": "The distribution of cytochrome c oxidase monoamine oxidase and lactate dehydrogenase, together with protein, after isopycnic centrifugation of a crude mitochondrial fraction of chick telencephalon homogenate in a linear sucrose density gradient, was followed during late embryogenesis and postnatal maturation. Two main populations of subcellular organelles differentiate; they were characterized biochemically and analyzed by electron microscopy. One population, with a progressively defined mean buoyant density of 1.170 g/ml, exhibited a high relative activity of monoamine oxidase, with a low and relatively constant cytochrome c oxidase/monoamine oxidase activity ratio. This population was composed of free mitochondria and mitochondria enclosed in nerve endings, and possibly of mitochondria of perikaryal and glial origin. A second population, with a progressively well defined mean buoyant density of 1.182-1.186 g/ml, exhibited a high relative activity of cytochrome c oxidase, with a high and increasing cytochrome c oxidase/monoamine oxidase activity ratio. The biochemical and functional significance of these results were discussed.", "contents": "Subcellular distribution of cytochrome c oxidase, monoamine oxidase and lactate dehydrogenase in the developing chick telencephalon. The distribution of cytochrome c oxidase monoamine oxidase and lactate dehydrogenase, together with protein, after isopycnic centrifugation of a crude mitochondrial fraction of chick telencephalon homogenate in a linear sucrose density gradient, was followed during late embryogenesis and postnatal maturation. Two main populations of subcellular organelles differentiate; they were characterized biochemically and analyzed by electron microscopy. One population, with a progressively defined mean buoyant density of 1.170 g/ml, exhibited a high relative activity of monoamine oxidase, with a low and relatively constant cytochrome c oxidase/monoamine oxidase activity ratio. This population was composed of free mitochondria and mitochondria enclosed in nerve endings, and possibly of mitochondria of perikaryal and glial origin. A second population, with a progressively well defined mean buoyant density of 1.182-1.186 g/ml, exhibited a high relative activity of cytochrome c oxidase, with a high and increasing cytochrome c oxidase/monoamine oxidase activity ratio. The biochemical and functional significance of these results were discussed."}
{"id": "PMID:191143", "title": "Iontophoretic application of opiates to the locus coeruleus.", "content": "The vast majority of morphine-sensitive single units in the area examined were localized to the locus coeruleus. This corresponds well with the known distribution of the highest densities of opiate receptor sites in this region of the midbrain. The effect of iontophoretically applied morphine was a marked and prolonged depression of spontaneous activity. Levorphanol, an opiate agonist, produced an effect similar to that of morphine while comparable doses of dextrorphan, it's clinically inactive stereoisomer, did not. Naloxone and levallorphan prevented as well as reversed the depression due to application of agonists. While the units were depressed following the application of opiate agonists, the cells were still excited by the neurotransmitter acetylcholine. We conclude that (1) neuronal sensitivity to opiates has a high positive correlation with autoradiographically determined opiate receptor sites, and (2) this sensitivity to opiates is blocked by opiate antagonists and is stereospecific in nature.", "contents": "Iontophoretic application of opiates to the locus coeruleus. The vast majority of morphine-sensitive single units in the area examined were localized to the locus coeruleus. This corresponds well with the known distribution of the highest densities of opiate receptor sites in this region of the midbrain. The effect of iontophoretically applied morphine was a marked and prolonged depression of spontaneous activity. Levorphanol, an opiate agonist, produced an effect similar to that of morphine while comparable doses of dextrorphan, it's clinically inactive stereoisomer, did not. Naloxone and levallorphan prevented as well as reversed the depression due to application of agonists. While the units were depressed following the application of opiate agonists, the cells were still excited by the neurotransmitter acetylcholine. We conclude that (1) neuronal sensitivity to opiates has a high positive correlation with autoradiographically determined opiate receptor sites, and (2) this sensitivity to opiates is blocked by opiate antagonists and is stereospecific in nature."}
{"id": "PMID:191145", "title": "The effect of capsaicin on the adenylate cyclase activity of rat brain.", "content": "The effect of capsaicin on the adenylate cyclase activity in different regions of the rat brain (preoptic area of the hypothalamus, cerebral cortex and cerebellum) was investigated. Capsaicin added in vitro (10(-7)-10(-5) M) increased the adenylate cyclase activity of different brain regions. Following systemic capsaicin desensitization adenylate cyclase activity was significantly increased in the preoptic area. The enhanced adenylate cyclase activity in the preoptic area was inhibited by the vitro addition of capsaicin or 5-HT, whereas desensitization did not affect the in vitro activating effect of capsaicin in other brain regions (cerebral cortex, cerebellum). It is assumed that the pharmacological effect of capsaicin in the preoptic area is mediated through the activation of adenylate cyclase. Since capsaicin induces irreversible impairment of the function of warmsensitive hypothalamic neurons it is assumed that adenylate cyclase is involved in maintaining normal thermoregulatory functions.", "contents": "The effect of capsaicin on the adenylate cyclase activity of rat brain. The effect of capsaicin on the adenylate cyclase activity in different regions of the rat brain (preoptic area of the hypothalamus, cerebral cortex and cerebellum) was investigated. Capsaicin added in vitro (10(-7)-10(-5) M) increased the adenylate cyclase activity of different brain regions. Following systemic capsaicin desensitization adenylate cyclase activity was significantly increased in the preoptic area. The enhanced adenylate cyclase activity in the preoptic area was inhibited by the vitro addition of capsaicin or 5-HT, whereas desensitization did not affect the in vitro activating effect of capsaicin in other brain regions (cerebral cortex, cerebellum). It is assumed that the pharmacological effect of capsaicin in the preoptic area is mediated through the activation of adenylate cyclase. Since capsaicin induces irreversible impairment of the function of warmsensitive hypothalamic neurons it is assumed that adenylate cyclase is involved in maintaining normal thermoregulatory functions."}
{"id": "PMID:191148", "title": "Cyclic AMP and ultrastructural organization of the nerve cell nucleus: stimulation of nuclear microtubules and microfilaments assembly in sympathetic neurons.", "content": "As we have previously shown for electrical stimulation, in vivo cyclic AMP analogues and theophylline induce an increase (up to 8.5-fold) in the frequency of microtubular-microfilamentous inclusions in the nucleus of sympathetic neurons. These drugs, like electrical stimulation, do not modify the ultrastructural organization of such inclusions, which is briefly reviewed in the present study with the help of tilting experiments. Such data consistent with our previous opinion that microtubules and microfilaments are normal nuclear constituents of these nerve cells, their frequency being related to physiological activity. Moreover, our results may now be discussed in terms of the relationship between these nuclear inclusions and the physiological modulation of transmission through the sympathetic ganglion. Finally, as recently demonstrated in the cytoplasm, the present study shows for the first time that cyclic AMP promotes the assembly of microtubules and microfilaments in the nuclear compartment.", "contents": "Cyclic AMP and ultrastructural organization of the nerve cell nucleus: stimulation of nuclear microtubules and microfilaments assembly in sympathetic neurons. As we have previously shown for electrical stimulation, in vivo cyclic AMP analogues and theophylline induce an increase (up to 8.5-fold) in the frequency of microtubular-microfilamentous inclusions in the nucleus of sympathetic neurons. These drugs, like electrical stimulation, do not modify the ultrastructural organization of such inclusions, which is briefly reviewed in the present study with the help of tilting experiments. Such data consistent with our previous opinion that microtubules and microfilaments are normal nuclear constituents of these nerve cells, their frequency being related to physiological activity. Moreover, our results may now be discussed in terms of the relationship between these nuclear inclusions and the physiological modulation of transmission through the sympathetic ganglion. Finally, as recently demonstrated in the cytoplasm, the present study shows for the first time that cyclic AMP promotes the assembly of microtubules and microfilaments in the nuclear compartment."}
{"id": "PMID:191149", "title": "Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla.", "content": "The localization of opiate receptors in the spinal cord and lower medulla has been elucidated by the autoradiographic identification of stereospecific [3H]diprenorphine (a potent opiate antagonist) binding sites. The opiate receptors were higly localized to: layers I (marginal cell zones) and II (substantia gelatinosa) of the dorsal horn of the spinal cord; the substantia gelationsa of the spinal trigeminal nucleus; components of the vagal system, including the vagus nerve, nucleus tractus solitarius, nucleus commissuralis, nucleus intercalatus, nucleus ambiguus and nucleus originis dorsalis vagus; the area postrema. Examination of [3H]etorphine (a potent opiate agonist) binding sites showed the same distribution. We conclude that, in these brain regions, opiate receptors are (1) highly associated with areas receiving small, afferent primary fibers, (2) strategically placed to modulate noxious stimuli as well as explain some visceral side effects of opiate administration.", "contents": "Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla. The localization of opiate receptors in the spinal cord and lower medulla has been elucidated by the autoradiographic identification of stereospecific [3H]diprenorphine (a potent opiate antagonist) binding sites. The opiate receptors were higly localized to: layers I (marginal cell zones) and II (substantia gelatinosa) of the dorsal horn of the spinal cord; the substantia gelationsa of the spinal trigeminal nucleus; components of the vagal system, including the vagus nerve, nucleus tractus solitarius, nucleus commissuralis, nucleus intercalatus, nucleus ambiguus and nucleus originis dorsalis vagus; the area postrema. Examination of [3H]etorphine (a potent opiate agonist) binding sites showed the same distribution. We conclude that, in these brain regions, opiate receptors are (1) highly associated with areas receiving small, afferent primary fibers, (2) strategically placed to modulate noxious stimuli as well as explain some visceral side effects of opiate administration."}
{"id": "PMID:191150", "title": "Evaluation of the periaqueductal central gray (PAG) as a morphine-specific locus of action and examination of morphine-induced and stimulation-produced analgesia at coincident PAG loci.", "content": "Experiments were carried out in rats to (1) elaborate upon the sepcificity of drug action in the periaqueductal gray matter (PAG), and (2) to evaluate the posible congruence of PAG sites of morphine-induced and stimulation-produced analgesis (SPA) applied at virtually identical PAG loci. It was demonstrated that the effect of morphine intracerebrally (i,c.) administered into the PAG was not duplicated by other centrally acting agents (chlorpromazine, chlordiazepoxide, pentobarbital or naloxone) administered i.c. at the same PAG site. This selective action of morphine in the PAG was further demonstrated not to be test-bound since morphine significantly altered responding in all four of the analgesiometric tests employed. Thus, multiple i.c. injections of drugs at the same PAG locus were useful in demonstrating site specificity of drug action where behavioral and electroencephalographic methods alone had previously provided ambiguous information. Morphine-induced analgesia and SPA, evaluated at virtually coincident PAG sites, revealed only a general congruence of efficacious loci. The most effective PAG loci for morphine-induced analgesia were not the same as those for SPA; analgesia effected by one analgesia-producing manipulation did not reliably predict that analgesia would also be produced by the other analgesia-producing manipulation at the PAG sites examined. In general, the more efficacious analgesia-producing PAG loci were localized in the ventral-ventrolateral PAG.", "contents": "Evaluation of the periaqueductal central gray (PAG) as a morphine-specific locus of action and examination of morphine-induced and stimulation-produced analgesia at coincident PAG loci. Experiments were carried out in rats to (1) elaborate upon the sepcificity of drug action in the periaqueductal gray matter (PAG), and (2) to evaluate the posible congruence of PAG sites of morphine-induced and stimulation-produced analgesis (SPA) applied at virtually identical PAG loci. It was demonstrated that the effect of morphine intracerebrally (i,c.) administered into the PAG was not duplicated by other centrally acting agents (chlorpromazine, chlordiazepoxide, pentobarbital or naloxone) administered i.c. at the same PAG site. This selective action of morphine in the PAG was further demonstrated not to be test-bound since morphine significantly altered responding in all four of the analgesiometric tests employed. Thus, multiple i.c. injections of drugs at the same PAG locus were useful in demonstrating site specificity of drug action where behavioral and electroencephalographic methods alone had previously provided ambiguous information. Morphine-induced analgesia and SPA, evaluated at virtually coincident PAG sites, revealed only a general congruence of efficacious loci. The most effective PAG loci for morphine-induced analgesia were not the same as those for SPA; analgesia effected by one analgesia-producing manipulation did not reliably predict that analgesia would also be produced by the other analgesia-producing manipulation at the PAG sites examined. In general, the more efficacious analgesia-producing PAG loci were localized in the ventral-ventrolateral PAG."}
{"id": "PMID:191151", "title": "Independent receptors for pressor and drinking responses to central injections of angiotensin II and carbachol.", "content": "Angiotensin II and carbachol when injected in the brain ventricles of the rat produce similar responses of an increase in blood pressure and drinking behavior. The question of whether these effects are produced by independent receptors or via a cholinergic circuit is debatable for the drinking behavior and evidence is lacking for the blood pressure effect. We have used a chronic rat preparation for recording blood pressure and drinking at the same time during intraventricular injections (i.v.t.) of both angiotensin and carbachol and i.v.t. or intravenous infusions of appropriate antagonists. The results show that drinking and blood pressure response to angiotensin II can be blocked by P113 (500 ng 1.v.t.) an angiotensin antagonist; they are not blocked by atropine (10 mug i.v.t.) a cholinergic antagonist; carbachol effects, however, are not blocked by P113, but are totally blocked by atropine (10 mug i.v.t.), At high doses of atropine there is inhibition of both agents but this probably represents a general inhibition. The hormone and cholinomimetic administered together interact and both are inhibited by adrenergic stimulation. We conclude from these experiments that angiotensin and carbachol act upon independent receptors in the brain to produce blood pressure and drinking responses but at some point they share common, central effector pathways.", "contents": "Independent receptors for pressor and drinking responses to central injections of angiotensin II and carbachol. Angiotensin II and carbachol when injected in the brain ventricles of the rat produce similar responses of an increase in blood pressure and drinking behavior. The question of whether these effects are produced by independent receptors or via a cholinergic circuit is debatable for the drinking behavior and evidence is lacking for the blood pressure effect. We have used a chronic rat preparation for recording blood pressure and drinking at the same time during intraventricular injections (i.v.t.) of both angiotensin and carbachol and i.v.t. or intravenous infusions of appropriate antagonists. The results show that drinking and blood pressure response to angiotensin II can be blocked by P113 (500 ng 1.v.t.) an angiotensin antagonist; they are not blocked by atropine (10 mug i.v.t.) a cholinergic antagonist; carbachol effects, however, are not blocked by P113, but are totally blocked by atropine (10 mug i.v.t.), At high doses of atropine there is inhibition of both agents but this probably represents a general inhibition. The hormone and cholinomimetic administered together interact and both are inhibited by adrenergic stimulation. We conclude from these experiments that angiotensin and carbachol act upon independent receptors in the brain to produce blood pressure and drinking responses but at some point they share common, central effector pathways."}
{"id": "PMID:191154", "title": "Biodegradation of alpha-MSH and derived peptides by rat brain extracts, and by rat and human serum.", "content": "The peptides alpha-MSH and MSH/ACTH 4-10 were degraded by rat brain extracts and serum to yield free amino acids among the end-products. Breakdown of these two peptides was double that of a related synthetic hexapeptide Met (0)-Glu-His-Phe-D-Lys-Phe. No significant breakdown of the hexapeptide occurred after incubation with human serum; it also had almost negligible pigmentary effects in vivo and in vitro when compared to alpha-MSH. The patterns of amino acid release indicate possible endopeptidase cleavage at Phe-Arg in alpha-MSH followed by secondary exopeptidase action to release free amino acids. For the hexapeptide, the primary cleavage point occurred at the -His3-Phe4 bond. The stability of this analog in human sera, coupled with its lower rate of degradation in the CNS, may contribute to its more potent behavioral actions in vivo.", "contents": "Biodegradation of alpha-MSH and derived peptides by rat brain extracts, and by rat and human serum. The peptides alpha-MSH and MSH/ACTH 4-10 were degraded by rat brain extracts and serum to yield free amino acids among the end-products. Breakdown of these two peptides was double that of a related synthetic hexapeptide Met (0)-Glu-His-Phe-D-Lys-Phe. No significant breakdown of the hexapeptide occurred after incubation with human serum; it also had almost negligible pigmentary effects in vivo and in vitro when compared to alpha-MSH. The patterns of amino acid release indicate possible endopeptidase cleavage at Phe-Arg in alpha-MSH followed by secondary exopeptidase action to release free amino acids. For the hexapeptide, the primary cleavage point occurred at the -His3-Phe4 bond. The stability of this analog in human sera, coupled with its lower rate of degradation in the CNS, may contribute to its more potent behavioral actions in vivo."}
{"id": "PMID:191155", "title": "Pentobarbital and synaptic high-affinity receptive sites for gamma-aminobutyric acid.", "content": "Electrophysiological investigations of others show that pentobarbital enhances the inhibitory inflences of gamma-aminobutyric acid (GABA). Specifically, receptor activation is amplified and prolonged, suggesting the presence of an increased number of GABA molecules in the synaptic cleft. Either inactivation of high-affinity GABA transport or alteration of post-synaptic GABA receptors might account for these influences of pentobarbital. In this sudy the effect of pentobarbital on high-affinity uptake and binding of GABA to synaptic receptive sites has been examined. Using synaptosomes and subsynaptosomal fractions of cerebral cortex and hippocampus, it si shown that concentrations of pentobarbital, exceeding 1 mM have no appreciable effect on GABA uptake or binding. Thus the synaptic influence of pentobarbital, evident at 0.1 mM in electrophysiologic experiments, must originate from mechanisms other than the high-affinity uptake or binding of GABA. Possible sites of action include the presynaptic release of GABA and the ionophores coupled with postsynapitc sites.", "contents": "Pentobarbital and synaptic high-affinity receptive sites for gamma-aminobutyric acid. Electrophysiological investigations of others show that pentobarbital enhances the inhibitory inflences of gamma-aminobutyric acid (GABA). Specifically, receptor activation is amplified and prolonged, suggesting the presence of an increased number of GABA molecules in the synaptic cleft. Either inactivation of high-affinity GABA transport or alteration of post-synaptic GABA receptors might account for these influences of pentobarbital. In this sudy the effect of pentobarbital on high-affinity uptake and binding of GABA to synaptic receptive sites has been examined. Using synaptosomes and subsynaptosomal fractions of cerebral cortex and hippocampus, it si shown that concentrations of pentobarbital, exceeding 1 mM have no appreciable effect on GABA uptake or binding. Thus the synaptic influence of pentobarbital, evident at 0.1 mM in electrophysiologic experiments, must originate from mechanisms other than the high-affinity uptake or binding of GABA. Possible sites of action include the presynaptic release of GABA and the ionophores coupled with postsynapitc sites."}
{"id": "PMID:191158", "title": "Effect of sodium nitroprusside and trimetaphan on neuromuscular transmission in the frog.", "content": "In summary, it appears from this and other studies that trimetaphan has the potential for producing neuromuscular blockade when used in large doses or when combined with other muscle relaxants. The mode of action appears to be principally that of non-depolarizing neuromuscular blockade. Sodium nitroprusside, on the other hand, even in doses beyond these accepted clinically, does not affect neuromuscular transmission and unless otherwise contraindicated is safe to use with muscle relaxants.", "contents": "Effect of sodium nitroprusside and trimetaphan on neuromuscular transmission in the frog. In summary, it appears from this and other studies that trimetaphan has the potential for producing neuromuscular blockade when used in large doses or when combined with other muscle relaxants. The mode of action appears to be principally that of non-depolarizing neuromuscular blockade. Sodium nitroprusside, on the other hand, even in doses beyond these accepted clinically, does not affect neuromuscular transmission and unless otherwise contraindicated is safe to use with muscle relaxants."}
{"id": "PMID:191152", "title": "Electrophysiological connections of the rat mediobasal hypothalamus with brain areas mediating adrenocortical responses.", "content": "With the purpose of correlating neuroendocrine and neurophysiological data, the effects of stimulating brain areas which have been shown to be involved in the mediation of adrenocortical reponses, i.e. pontine reticular formation (PRF), mammillary peduncle (MP), medial forebrain bundle (MFB), and the suprachiasmatic nucleus (SCN), were studied on unit activity in the mediobasal hypothalamus in the rat. About half of the units recorded responded significantly to one of these modalities by a change in the rate of firing, the MP producing mainly inhibition and SCN facilitation and changes also occurred in the post-stimulus histograms. There was a convergence of different modalities on the same hypothalamic unit. No changes occurred in the time-interval histograms. Stimulating the mediobasal hypothalamus activated synaptically units in the PRF, MP, and MFB but none of them were activated antidromically. The present data demonstrate electrophysiological connections between extrahypothalamic regions participating in adrenocortical regulation and the hypophysiotropic area of the hypothalamus.", "contents": "Electrophysiological connections of the rat mediobasal hypothalamus with brain areas mediating adrenocortical responses. With the purpose of correlating neuroendocrine and neurophysiological data, the effects of stimulating brain areas which have been shown to be involved in the mediation of adrenocortical reponses, i.e. pontine reticular formation (PRF), mammillary peduncle (MP), medial forebrain bundle (MFB), and the suprachiasmatic nucleus (SCN), were studied on unit activity in the mediobasal hypothalamus in the rat. About half of the units recorded responded significantly to one of these modalities by a change in the rate of firing, the MP producing mainly inhibition and SCN facilitation and changes also occurred in the post-stimulus histograms. There was a convergence of different modalities on the same hypothalamic unit. No changes occurred in the time-interval histograms. Stimulating the mediobasal hypothalamus activated synaptically units in the PRF, MP, and MFB but none of them were activated antidromically. The present data demonstrate electrophysiological connections between extrahypothalamic regions participating in adrenocortical regulation and the hypophysiotropic area of the hypothalamus."}
{"id": "PMID:191159", "title": "The beta-glucosidases of porcine kidney.", "content": "Some of the properties of a partially purified particle bound and soluble beta-glucosidase (EC 3.2.1.21) from pig kidney were compared. The soluble beta-glucosidase (1) hydrolyzed 4-methylumbelliferyl-beta-D-glucoside (4-MU-beta-D-glucoside) 17 alpha-estradiol 3beta-glucoside. 17 alpha-estradiol 17beta-glucoside, and salicin, but not glucosylceramide, (2) possessed a broad pH optimum (5.5-7.0), (3) had an isoelectric point of 4.9, and (4) was inhibited by Triton X-100. Several compounds were found to be competitive inhibitors of its hydrolytic activity, gluconolactam and estrone beta-glucoside being the most effective. In contrast, a particulate beta-glucodidase purified from the same tissue (1) had an acidic pH optimum (5.0), (2) was stimulated by sodium taurocholate and 'Gaucher's factor' for the hydrolysis of both 4-MU-beta-glucosidase and glucosylceramide, and (3) was capable of catalyzing a transglucosylation reaction employing 4-MU-beta-D-glucoside or glucosylceramide as the glucosyl donor, and [14C]ceramide as acceptor.", "contents": "The beta-glucosidases of porcine kidney. Some of the properties of a partially purified particle bound and soluble beta-glucosidase (EC 3.2.1.21) from pig kidney were compared. The soluble beta-glucosidase (1) hydrolyzed 4-methylumbelliferyl-beta-D-glucoside (4-MU-beta-D-glucoside) 17 alpha-estradiol 3beta-glucoside. 17 alpha-estradiol 17beta-glucoside, and salicin, but not glucosylceramide, (2) possessed a broad pH optimum (5.5-7.0), (3) had an isoelectric point of 4.9, and (4) was inhibited by Triton X-100. Several compounds were found to be competitive inhibitors of its hydrolytic activity, gluconolactam and estrone beta-glucoside being the most effective. In contrast, a particulate beta-glucodidase purified from the same tissue (1) had an acidic pH optimum (5.0), (2) was stimulated by sodium taurocholate and 'Gaucher's factor' for the hydrolysis of both 4-MU-beta-glucosidase and glucosylceramide, and (3) was capable of catalyzing a transglucosylation reaction employing 4-MU-beta-D-glucoside or glucosylceramide as the glucosyl donor, and [14C]ceramide as acceptor."}
{"id": "PMID:191160", "title": "Ion binding to lysine-modified derivatives of cytochrome c.", "content": "The effect of Cl- and K+ ions on the apparent equilibrium constant of the reaction between horse ferricytochrome c and potassium ferrocyanide was studied. Unmodified cytochrome was compared with two lysine-modified derivatives. One, guanidinated, had all lysyl groups converted to homoarginine (but retained the same positive charge); the other was trinitrophenylated at one lysine (measured spectrophotometrically). Both modified derivatives had a somewhat larger equilibrium constant in the reaction of the reduced protein with ferricyanide, but, unlike trifluoroacetylated cytochrome c (which has a negative charge), the redox properties were not dramatically different. The native protein and the lysine-modified cytochromes showed differential K+ binding in Tris-cacodylate buffer at constant ionic strength (0.003-0.005 M). More K+ was bound to ferrocytochrome c. This redox-linked binding, however, was unaffected by modification of lysine. All three derivatives also showed redox-linked differential Cl- ion binding (more Cl- ion was bount to ferricytochrome); however, in this case, the binding was reduced in the lysine-modified molecules. This was interpreted as loss of a single anion site. This anion site critically depends on one or a few lysines which are more reactive with trinitrobenzene sulfonate.", "contents": "Ion binding to lysine-modified derivatives of cytochrome c. The effect of Cl- and K+ ions on the apparent equilibrium constant of the reaction between horse ferricytochrome c and potassium ferrocyanide was studied. Unmodified cytochrome was compared with two lysine-modified derivatives. One, guanidinated, had all lysyl groups converted to homoarginine (but retained the same positive charge); the other was trinitrophenylated at one lysine (measured spectrophotometrically). Both modified derivatives had a somewhat larger equilibrium constant in the reaction of the reduced protein with ferricyanide, but, unlike trifluoroacetylated cytochrome c (which has a negative charge), the redox properties were not dramatically different. The native protein and the lysine-modified cytochromes showed differential K+ binding in Tris-cacodylate buffer at constant ionic strength (0.003-0.005 M). More K+ was bound to ferrocytochrome c. This redox-linked binding, however, was unaffected by modification of lysine. All three derivatives also showed redox-linked differential Cl- ion binding (more Cl- ion was bount to ferricytochrome); however, in this case, the binding was reduced in the lysine-modified molecules. This was interpreted as loss of a single anion site. This anion site critically depends on one or a few lysines which are more reactive with trinitrobenzene sulfonate."}
{"id": "PMID:191156", "title": "Method for reliably recording geniculate spikes during paradoxical sleep in the cat.", "content": "A simple procedure is described which allows an investigator to implant electrodes which will reliably record phasic spikes in the lateral geniculate nucleus during paradoxical sleep. This procedure relies on recording photically evoked activity during the implantation of the geniculate electrode and the fact that the distribution of such activity and phasic spikes during paradoxical sleep overlap within the lateral geniculate nucleus. The largest geniculate spikes were recorded during paradoxical sleep when an electrode recorded a large initially positive photically evoked potential and was positioned in the optic tract just ventral to the lateral geniculate nucleus.", "contents": "Method for reliably recording geniculate spikes during paradoxical sleep in the cat. A simple procedure is described which allows an investigator to implant electrodes which will reliably record phasic spikes in the lateral geniculate nucleus during paradoxical sleep. This procedure relies on recording photically evoked activity during the implantation of the geniculate electrode and the fact that the distribution of such activity and phasic spikes during paradoxical sleep overlap within the lateral geniculate nucleus. The largest geniculate spikes were recorded during paradoxical sleep when an electrode recorded a large initially positive photically evoked potential and was positioned in the optic tract just ventral to the lateral geniculate nucleus."}
{"id": "PMID:191153", "title": "Blood-brain barrier, half-time disappearance, and brain distribution for labeled enkephalin and a potent analog.", "content": "The natural opiate methionine-enkephalin and its D-alanine2 analog were iodinated by a method involving lactoperoxidase and purified by partition chromatography on Sephadex G-25. The half-time disappearance of radioactivity was determined in blood obtained from the jugular vein after injection of the iodinated methionine-enkephalin into the carotid artery or jugular vein and found to be less than a minute. Despite a greater potency and more prolonged activity of D-alanime2-methionine-enkephalin as compared with methionine-enkephalin, the half-time disappearance of radioactivity after injection of the iodinated analog was about the same, its distribution volume tended to be smaller, and the retention of counts in the brain was significantly less then after the iodinated parent compound. There was little statistical difference in the accumulation of radioactivity among nine brain regions 5 sec after the rapid injection of tritiated methionine-enkephalin into the carotid artery in contrast with the accumulation found after similar injection of tritiated tyrosine or tritiated water. The ratio of radioactivity in the pituitary or pineal to that in the brain parts within the blood-brain barrier was much greater after administration of the tritiated enkephalin than after the tritiated water. A modified brain-uptake index (BUI) value of 15 for the tritiated enkephalin indicates that methionine-enkephalin crosses the blood-brain barrier.", "contents": "Blood-brain barrier, half-time disappearance, and brain distribution for labeled enkephalin and a potent analog. The natural opiate methionine-enkephalin and its D-alanine2 analog were iodinated by a method involving lactoperoxidase and purified by partition chromatography on Sephadex G-25. The half-time disappearance of radioactivity was determined in blood obtained from the jugular vein after injection of the iodinated methionine-enkephalin into the carotid artery or jugular vein and found to be less than a minute. Despite a greater potency and more prolonged activity of D-alanime2-methionine-enkephalin as compared with methionine-enkephalin, the half-time disappearance of radioactivity after injection of the iodinated analog was about the same, its distribution volume tended to be smaller, and the retention of counts in the brain was significantly less then after the iodinated parent compound. There was little statistical difference in the accumulation of radioactivity among nine brain regions 5 sec after the rapid injection of tritiated methionine-enkephalin into the carotid artery in contrast with the accumulation found after similar injection of tritiated tyrosine or tritiated water. The ratio of radioactivity in the pituitary or pineal to that in the brain parts within the blood-brain barrier was much greater after administration of the tritiated enkephalin than after the tritiated water. A modified brain-uptake index (BUI) value of 15 for the tritiated enkephalin indicates that methionine-enkephalin crosses the blood-brain barrier."}
{"id": "PMID:191161", "title": "Temperature-induced changes in lecithin model membranes detected by novel covalent spin-labelled phospholipids.", "content": "Several spin-labelled phospholipids carrying covalently bound 5-doxylstearic acid (2-(3-carboxydecyl)-2-hexyl-4,4-dimethyl-3-oxazolidinoxyl) were intercalated in liposomes of saturated and unsaturated lecithins. Temperature-induced changes of these liposomes, detected by the spin-labelled phospholipids, were found to be in agreement with the previously described transitions of hydrocarbon chains of host lecithins detected by different probes and different techniques, establishing that spin-labelled phosopholipids are sensitive probes for the detection of temperature-induced changes in lecithin model membranes. In addition to the detection of already-known transitions in lecithin liposomes, the coexistence of two distinctly different enviroments was observed above the characteristic transition temperature. This phenomenon was tentatively attributed to the influence of the lecithin polar group on the fluidity of fatty acyl chains near the polar group. Combined with other results from the literature, the coexistence of two environments could be associated with the coexistence of two conformational isomers of lecithin, differing in the orientation of the polar head group with respect to the plane of bilayer. These findings have been discussed in view of the present state of knowledge regarding temperature-induced changes in model membranes.", "contents": "Temperature-induced changes in lecithin model membranes detected by novel covalent spin-labelled phospholipids. Several spin-labelled phospholipids carrying covalently bound 5-doxylstearic acid (2-(3-carboxydecyl)-2-hexyl-4,4-dimethyl-3-oxazolidinoxyl) were intercalated in liposomes of saturated and unsaturated lecithins. Temperature-induced changes of these liposomes, detected by the spin-labelled phospholipids, were found to be in agreement with the previously described transitions of hydrocarbon chains of host lecithins detected by different probes and different techniques, establishing that spin-labelled phosopholipids are sensitive probes for the detection of temperature-induced changes in lecithin model membranes. In addition to the detection of already-known transitions in lecithin liposomes, the coexistence of two distinctly different enviroments was observed above the characteristic transition temperature. This phenomenon was tentatively attributed to the influence of the lecithin polar group on the fluidity of fatty acyl chains near the polar group. Combined with other results from the literature, the coexistence of two environments could be associated with the coexistence of two conformational isomers of lecithin, differing in the orientation of the polar head group with respect to the plane of bilayer. These findings have been discussed in view of the present state of knowledge regarding temperature-induced changes in model membranes."}
{"id": "PMID:191162", "title": "Selective enzymatic radioactive and spin labelling of phospholipids in biological membranes: application to study of temperature-induced changes of microsomal phosphatidylinositols and mitochondrial polyglycerophosphatides.", "content": "A new method for the covalent radioactive and spin labelling of lipids within isolated biological membranes has been described in detail and applied to studies of temperature-induced changes of microsomal and mitochondrial membranes. The method is based on the enzymatic use of radioactive substrates carrying covalently bound doxyl derivatives of stearic acid in the biosynthesis of phospholipids in isolated membranes. Radioactive-and spin-labelled lipids bound to the microsomal and mitochondrial membranes were then used as internal probes in monitoring temperature-induced changes of these membranes. Since the analysis of isolated radioactive-and spin-labelled lipids revealed the exact composition of membrane-bound labelled lipids, specific temperature-induced changes were correlated with specific lipids of examined membranes. Phosphatidylinositol of microsomal membranes and polyglycerophosphatides (phosphatidyl-glycerol and cardiolipin) of mitochondrial and inner mitochondrial membranes were found to be involved in the apparent formation of lipid clusters at around 20-30 degrees C. Cardiolipin was found to be involved in the fluidization of inner mitochondrial membranes. These findings are discussed in view of the present state of knowledge of the organization of lipids in biological membranes.", "contents": "Selective enzymatic radioactive and spin labelling of phospholipids in biological membranes: application to study of temperature-induced changes of microsomal phosphatidylinositols and mitochondrial polyglycerophosphatides. A new method for the covalent radioactive and spin labelling of lipids within isolated biological membranes has been described in detail and applied to studies of temperature-induced changes of microsomal and mitochondrial membranes. The method is based on the enzymatic use of radioactive substrates carrying covalently bound doxyl derivatives of stearic acid in the biosynthesis of phospholipids in isolated membranes. Radioactive-and spin-labelled lipids bound to the microsomal and mitochondrial membranes were then used as internal probes in monitoring temperature-induced changes of these membranes. Since the analysis of isolated radioactive-and spin-labelled lipids revealed the exact composition of membrane-bound labelled lipids, specific temperature-induced changes were correlated with specific lipids of examined membranes. Phosphatidylinositol of microsomal membranes and polyglycerophosphatides (phosphatidyl-glycerol and cardiolipin) of mitochondrial and inner mitochondrial membranes were found to be involved in the apparent formation of lipid clusters at around 20-30 degrees C. Cardiolipin was found to be involved in the fluidization of inner mitochondrial membranes. These findings are discussed in view of the present state of knowledge of the organization of lipids in biological membranes."}
{"id": "PMID:191163", "title": "Lack of release of ACTH from the denervated rat pars intermedia in vivo.", "content": "The purpose of this study was to ascertain whether the pars intermedia of the rat adenohypophysis, isolated from direct innervation via the infundibular stem, could maintain adrenal cortical weight and plasma corticosterone levels. We compared the adrenal cortical response of rats 40 days after either complete hypophysectomy, hypophysectomy with reinsertion of only the pars distalis, or hypophysectomy with reinsertion of only the nervosa-intermedia. Adrenal weight and plasma corticosterone levels were partially maintained in the group with reinserted pars distalis. These parameters were not different from the complete hypophysectomy group in the animals with reinserted nervosa-intermedia. Thus, the pars intermedia, with its nerve supply disrupted, cannot maintain adrenal cortical function.", "contents": "Lack of release of ACTH from the denervated rat pars intermedia in vivo. The purpose of this study was to ascertain whether the pars intermedia of the rat adenohypophysis, isolated from direct innervation via the infundibular stem, could maintain adrenal cortical weight and plasma corticosterone levels. We compared the adrenal cortical response of rats 40 days after either complete hypophysectomy, hypophysectomy with reinsertion of only the pars distalis, or hypophysectomy with reinsertion of only the nervosa-intermedia. Adrenal weight and plasma corticosterone levels were partially maintained in the group with reinserted pars distalis. These parameters were not different from the complete hypophysectomy group in the animals with reinserted nervosa-intermedia. Thus, the pars intermedia, with its nerve supply disrupted, cannot maintain adrenal cortical function."}
{"id": "PMID:191164", "title": "Dispersed cell cultures of the rat pineal: growth and morphological differentiation.", "content": "A method is described for the preparation and growth of rat pineal monolayer cultures derived from both mature and immature animals. The cultures were observed to undergo profound but reversible morphological differentiations by addition of dibutyryl-cAMP, monobutyryl-cAMP, papaverine, prostaglandins, and adenosine, and by removal of serum. Sodium butyrate and theophylline had no effect. Time-lapse photography indicated that this reversible transformation took place via a contraction-relaxation mechanism. Both colcemid and cytochalasin B inhibited the transformation. These results demonstrate that this type of morphological transformation, previously demonstrated in tumour and embryonic cell cultures, can also occur in nonembryonic, non-neoplastic tissue, and may be related to a general dedifferentiative process occurring in monolayer cultures.", "contents": "Dispersed cell cultures of the rat pineal: growth and morphological differentiation. A method is described for the preparation and growth of rat pineal monolayer cultures derived from both mature and immature animals. The cultures were observed to undergo profound but reversible morphological differentiations by addition of dibutyryl-cAMP, monobutyryl-cAMP, papaverine, prostaglandins, and adenosine, and by removal of serum. Sodium butyrate and theophylline had no effect. Time-lapse photography indicated that this reversible transformation took place via a contraction-relaxation mechanism. Both colcemid and cytochalasin B inhibited the transformation. These results demonstrate that this type of morphological transformation, previously demonstrated in tumour and embryonic cell cultures, can also occur in nonembryonic, non-neoplastic tissue, and may be related to a general dedifferentiative process occurring in monolayer cultures."}
{"id": "PMID:191165", "title": "Regulation of glucagon-stimulated production of glucose in rat liver by guanosine 3',5'-cyclic phosphate.", "content": "Exogenous cGMP can inhibit both basal and glucagon-stimulated production of glucose in liver slices from fed rats. Thus, cAMP and cGMP have opposite effects on the production of glucose in rat liver. Acetylcholine, an activator of guanylate cyclase (EC 4.6.1.2) in other systems, also inhibits the glucagon-stimulated production of glucose. No effect on glucose production was observed with secretin or exogenous GTP.", "contents": "Regulation of glucagon-stimulated production of glucose in rat liver by guanosine 3',5'-cyclic phosphate. Exogenous cGMP can inhibit both basal and glucagon-stimulated production of glucose in liver slices from fed rats. Thus, cAMP and cGMP have opposite effects on the production of glucose in rat liver. Acetylcholine, an activator of guanylate cyclase (EC 4.6.1.2) in other systems, also inhibits the glucagon-stimulated production of glucose. No effect on glucose production was observed with secretin or exogenous GTP."}
{"id": "PMID:191166", "title": "Effect of praseodymium nitrate on hepatocytes and Kupffer cells in the rat.", "content": "Intravenous administration of the rare earth metal salt, praseodymium nitrate, induced hepatic damage in the rat, as assessed by morphologic examination (light and electron microscopy) and biochemical parameters (serum glutamic-pyruvic transaminase (EC 2.6.1.2) and glutamic-oxalacetic transaminase (EC 2.6.1.1) activity as well as hepatic triglyceride content). Praseodymium hepatotoxicity was only attained with lower doses (10, 20, or 40 mg/kg), whereas a larger dose (80 mg/kg) was inactive in this respect. As detected by electron microscopy, lower doses of the metal salt caused hepatocytic alterations consisting of degranulation and dilatation of rough endoplasmic reticulum, accumulation of smooth endoplasmic reticulum as well as numerous lipid droplets. No abnormalities were detected in the cell organelles following administration of a large dose of the metal salt; however, vacuoles containing markedly electron-dense material were seen in the cytoplasm of the hepatocytes and the sinusoidal Kupffer cells.", "contents": "Effect of praseodymium nitrate on hepatocytes and Kupffer cells in the rat. Intravenous administration of the rare earth metal salt, praseodymium nitrate, induced hepatic damage in the rat, as assessed by morphologic examination (light and electron microscopy) and biochemical parameters (serum glutamic-pyruvic transaminase (EC 2.6.1.2) and glutamic-oxalacetic transaminase (EC 2.6.1.1) activity as well as hepatic triglyceride content). Praseodymium hepatotoxicity was only attained with lower doses (10, 20, or 40 mg/kg), whereas a larger dose (80 mg/kg) was inactive in this respect. As detected by electron microscopy, lower doses of the metal salt caused hepatocytic alterations consisting of degranulation and dilatation of rough endoplasmic reticulum, accumulation of smooth endoplasmic reticulum as well as numerous lipid droplets. No abnormalities were detected in the cell organelles following administration of a large dose of the metal salt; however, vacuoles containing markedly electron-dense material were seen in the cytoplasm of the hepatocytes and the sinusoidal Kupffer cells."}
{"id": "PMID:191167", "title": "The site of the neuromuscular block produced by polymyxin B and rolitetracycline.", "content": "The site of neuromuscular blockade induced by polymyxin B and rolitetracycline was studied on isolated nerve and nerve-muscle preparations. Polymyxin B (1.8 X 10(-4) M) was equipotent to lidocaine as a local anaesthetic on a frog desheathed nerve preparation, while rolitetracycline (up to 3.6 X 10(-3)M) had no local anaesthetic effect. Polymyxin B (6 X 10(-5) M) and rolitetracycline (7 X 10(-4) M) blocked by 50% the response of rat diaphragm induced by phrenic nerve stimulation, but did not decrease the amount of acetylcholine (ACh) released from this preparation during nerve stimulation. Both antibiotics depressed the response of the rat diaphragm to inject ACh, and this response was more sensitive to inhibition by the drugs than was the response to nerve stimulation. With rolitetracycline, a concentration that blocked the response to nerve stimulation by 50% inhibited the response to injected ACh by 85%, and this relationship was similar to that with d-tubocurarine; however, polymyxin B was relatively more effective than d-tubocurarine in inhibiting the effect of ACh. Polymyxin B (1-1.5 X 10(-4) M) but not rolitetracycline (1 X 10(-3) M) depressed the response of the diaphragm to direct muscle stimulation. It is concluded that polymyxin B and rolitetracycline block neuromuscular transmission predominatly by an effect to depress the muscle's sensitivity to ACh; polymyxin B probably acts by an effect similar to that of local anaesthetics, while rolitetracycline probably acts by an effect similar to that of d-tubocurarine.", "contents": "The site of the neuromuscular block produced by polymyxin B and rolitetracycline. The site of neuromuscular blockade induced by polymyxin B and rolitetracycline was studied on isolated nerve and nerve-muscle preparations. Polymyxin B (1.8 X 10(-4) M) was equipotent to lidocaine as a local anaesthetic on a frog desheathed nerve preparation, while rolitetracycline (up to 3.6 X 10(-3)M) had no local anaesthetic effect. Polymyxin B (6 X 10(-5) M) and rolitetracycline (7 X 10(-4) M) blocked by 50% the response of rat diaphragm induced by phrenic nerve stimulation, but did not decrease the amount of acetylcholine (ACh) released from this preparation during nerve stimulation. Both antibiotics depressed the response of the rat diaphragm to inject ACh, and this response was more sensitive to inhibition by the drugs than was the response to nerve stimulation. With rolitetracycline, a concentration that blocked the response to nerve stimulation by 50% inhibited the response to injected ACh by 85%, and this relationship was similar to that with d-tubocurarine; however, polymyxin B was relatively more effective than d-tubocurarine in inhibiting the effect of ACh. Polymyxin B (1-1.5 X 10(-4) M) but not rolitetracycline (1 X 10(-3) M) depressed the response of the diaphragm to direct muscle stimulation. It is concluded that polymyxin B and rolitetracycline block neuromuscular transmission predominatly by an effect to depress the muscle's sensitivity to ACh; polymyxin B probably acts by an effect similar to that of local anaesthetics, while rolitetracycline probably acts by an effect similar to that of d-tubocurarine."}
{"id": "PMID:191168", "title": "Characterization of the neuromuscular block produced by clindamycin and lincomycin.", "content": "The site of neuromuscular blockade induced by clindamycin and lincomycin was studied on isolated nerve and nerve-muscle preparations. Clindamycin (3.6 X 10(-3) M) but not lincomycin (up to 1.5 X 10(-2) M) had a local anaesthetic effect on a frog desheathed nerve preparation. Clindamycin (8 X 10(-4) M) and lincomycin (4 X 10(-3) M) depressed the response of the rat diaphragm to nerve stimulation and to direct muscle stimulation in parallel. This indicated that the predominant neuromuscular blocking effect of these antibiotics was due to an effect on the muscle. Clindamycin was fivefold more potent than lincomycin in this effect, and the unionized form of both drugs was the active form. Lincomycin (4 X 10(-3) M) but not clindamycin (8 X 10(-4) M) also had some depressant effect on nerve-muscle transmission as indicated by the interaction of the effects of the antibiotics and d-tubocurarine. The significance of these findings is discussed in relation to the acute clinical toxicity of these antibiotics.", "contents": "Characterization of the neuromuscular block produced by clindamycin and lincomycin. The site of neuromuscular blockade induced by clindamycin and lincomycin was studied on isolated nerve and nerve-muscle preparations. Clindamycin (3.6 X 10(-3) M) but not lincomycin (up to 1.5 X 10(-2) M) had a local anaesthetic effect on a frog desheathed nerve preparation. Clindamycin (8 X 10(-4) M) and lincomycin (4 X 10(-3) M) depressed the response of the rat diaphragm to nerve stimulation and to direct muscle stimulation in parallel. This indicated that the predominant neuromuscular blocking effect of these antibiotics was due to an effect on the muscle. Clindamycin was fivefold more potent than lincomycin in this effect, and the unionized form of both drugs was the active form. Lincomycin (4 X 10(-3) M) but not clindamycin (8 X 10(-4) M) also had some depressant effect on nerve-muscle transmission as indicated by the interaction of the effects of the antibiotics and d-tubocurarine. The significance of these findings is discussed in relation to the acute clinical toxicity of these antibiotics."}
{"id": "PMID:191169", "title": "Endorphin activity in anterior, intermediate, and posterior pituitary.", "content": "The content of endogenous morphine-like substance in bovine pituitary and brain was determined by an opiate radioreceptor assay. The intermediate lobe was most concentrated in activity and the brain least concentrated. Most of the endorphin is obtained in a 120 000 g-min fraction from pituitary or brain homogenates.", "contents": "Endorphin activity in anterior, intermediate, and posterior pituitary. The content of endogenous morphine-like substance in bovine pituitary and brain was determined by an opiate radioreceptor assay. The intermediate lobe was most concentrated in activity and the brain least concentrated. Most of the endorphin is obtained in a 120 000 g-min fraction from pituitary or brain homogenates."}
{"id": "PMID:191170", "title": "Cerebellar cAMP levels following acute and chronic morphine administration.", "content": "Acute administration of morphine sulfate at 20 mg/kg decreased mouse cerebellar adenosine 3',5'-cyclic phosphate (cAMP) levels while not affecting cAMP phosphodiesterase (EC 3.1.4.17). The cAMP levels and cAMP phosphodiesterase activies were not affected by chronic treatment. However, cAMP levels increased during abrupt withdrawal both with and without naloxone precipitation, with cAMP phosphodiesterase activities being correspondingly decreased. Propanolol prevented the cAMP increase during abrupt withdrawal.", "contents": "Cerebellar cAMP levels following acute and chronic morphine administration. Acute administration of morphine sulfate at 20 mg/kg decreased mouse cerebellar adenosine 3',5'-cyclic phosphate (cAMP) levels while not affecting cAMP phosphodiesterase (EC 3.1.4.17). The cAMP levels and cAMP phosphodiesterase activies were not affected by chronic treatment. However, cAMP levels increased during abrupt withdrawal both with and without naloxone precipitation, with cAMP phosphodiesterase activities being correspondingly decreased. Propanolol prevented the cAMP increase during abrupt withdrawal."}
{"id": "PMID:191171", "title": "Nonshivering thermogenesis in the rat. I. The relation between drug-induced changes in thermogenesis and changes in the concentration of plasma cyclic AMP.", "content": "Barbital-sedated, cold-acclimated (CA) or warm-acclimated (WA) rats were given different doses and combinations of noradrenaline, theophylline, and the adrenergic-blocking agents propranolol and phentolamine, to stimulate or inhibit calorigenesis in various ways. To see whether the effects of these drugs on calorigenesis could be ascribed to effects on the adenylate cyclase (EC 4.6.1.1) - cyclic AMP system, and to try to assess thereby the significance of this system in the regulation of nonshivering thermogenesis (NST), changes in the concentration of plasma cyclic AMP were measured as an index (Broadus, A.E., Hardman, J.G., Kaminsky, N. I., Ball, J. H., Sutherland, E.W., and Liddle, G. W.: 1971. Ann. N.Y. Acad. Sci. 185, 50-60) of changes in tissue levels of cyclic AMP. In CA rats, which have a severalfold greater capacity for NST than WA rats, calorigenic responses to noradrenaline, theophylline, noradrenaline plus theophylline, or phentolamine plus theophylline were as much as four times larger than in WA rats, However, the changes in level of plasma cyclic AMP produced by each of these and other treatments were virtually the same for both groups. It would appear, therefore, that the difference between WA and CA rats in ability to produce heat by NST is not a function of the amplitude of changes in tissue levels of cyclic AMP. Nevertheless, it was also observed, and was particularly striking in CA rats, that when a drug or combination of drugs had a stimulatory, inhibitory, or synergistic effect on calorigenesis, it had a similar effect with respect to elevation of plasma cyclic AMP. Altogether, the results indicate that adenylate cyclase and cyclic AMP are likely to be participants in the regulation of NST in the rat, but that they would be subservient in this regard to whatever factors are responsible for acclimation-related differences in capacity for NST.", "contents": "Nonshivering thermogenesis in the rat. I. The relation between drug-induced changes in thermogenesis and changes in the concentration of plasma cyclic AMP. Barbital-sedated, cold-acclimated (CA) or warm-acclimated (WA) rats were given different doses and combinations of noradrenaline, theophylline, and the adrenergic-blocking agents propranolol and phentolamine, to stimulate or inhibit calorigenesis in various ways. To see whether the effects of these drugs on calorigenesis could be ascribed to effects on the adenylate cyclase (EC 4.6.1.1) - cyclic AMP system, and to try to assess thereby the significance of this system in the regulation of nonshivering thermogenesis (NST), changes in the concentration of plasma cyclic AMP were measured as an index (Broadus, A.E., Hardman, J.G., Kaminsky, N. I., Ball, J. H., Sutherland, E.W., and Liddle, G. W.: 1971. Ann. N.Y. Acad. Sci. 185, 50-60) of changes in tissue levels of cyclic AMP. In CA rats, which have a severalfold greater capacity for NST than WA rats, calorigenic responses to noradrenaline, theophylline, noradrenaline plus theophylline, or phentolamine plus theophylline were as much as four times larger than in WA rats, However, the changes in level of plasma cyclic AMP produced by each of these and other treatments were virtually the same for both groups. It would appear, therefore, that the difference between WA and CA rats in ability to produce heat by NST is not a function of the amplitude of changes in tissue levels of cyclic AMP. Nevertheless, it was also observed, and was particularly striking in CA rats, that when a drug or combination of drugs had a stimulatory, inhibitory, or synergistic effect on calorigenesis, it had a similar effect with respect to elevation of plasma cyclic AMP. Altogether, the results indicate that adenylate cyclase and cyclic AMP are likely to be participants in the regulation of NST in the rat, but that they would be subservient in this regard to whatever factors are responsible for acclimation-related differences in capacity for NST."}
{"id": "PMID:191172", "title": "The effect of theophylline on amine-induced cardiac cyclic AMP and cardiac contractile force.", "content": "In the isolated electrically driven rat atria, theophylline (5 X 10(-4)M) produced a small but significant increase in cyclic AMP content which was prevented by reserpine pretreatment. Theophylline was also found to exert a direct contractile effect, unrelated to cyclic AMP, in atria obtained from reserpine-pretreated animals. The norepinephrine inotropic response was attenuated after 3 min, enhanced after 15 min, and abolished after 60 min of exposure to theophylline (5 X 10(-4) M). The maximum phenylephrine inotropic response was not significantly changed after 15 min of exposure to theophylline; however, there was a slight shift to the left of the phenylephrine dose-response curve. The effect of theophylline on cyclic AMP appeared to be additive with the norepinephine and phenylephrine responses. The effect of theophylline on amine-induced cardiac cyclic AMP and contractile force showed no correlation between the contractile and the cyclic AMP effects at the different times tested. It is concluded that the inotropic effects of theophylline in rat atria are not mediated through cyclic AMP; instead, the methylxanthines may exert their effects on the heart through changes in calcium metabolism.", "contents": "The effect of theophylline on amine-induced cardiac cyclic AMP and cardiac contractile force. In the isolated electrically driven rat atria, theophylline (5 X 10(-4)M) produced a small but significant increase in cyclic AMP content which was prevented by reserpine pretreatment. Theophylline was also found to exert a direct contractile effect, unrelated to cyclic AMP, in atria obtained from reserpine-pretreated animals. The norepinephrine inotropic response was attenuated after 3 min, enhanced after 15 min, and abolished after 60 min of exposure to theophylline (5 X 10(-4) M). The maximum phenylephrine inotropic response was not significantly changed after 15 min of exposure to theophylline; however, there was a slight shift to the left of the phenylephrine dose-response curve. The effect of theophylline on cyclic AMP appeared to be additive with the norepinephine and phenylephrine responses. The effect of theophylline on amine-induced cardiac cyclic AMP and contractile force showed no correlation between the contractile and the cyclic AMP effects at the different times tested. It is concluded that the inotropic effects of theophylline in rat atria are not mediated through cyclic AMP; instead, the methylxanthines may exert their effects on the heart through changes in calcium metabolism."}
{"id": "PMID:191173", "title": "Symposium on diarrhea. 3. Investigation of chronic diarrhea.", "content": "The practical approach to the investigation of diarrhea must be logical and based on anatomic considerations. The site of the underlying disorder may be determined by the clinical picture, and the logic of investigation will be influenced by the history. Important specific investigation in a case of colonic diarrhea include a careful rectal examination, stool inspection, sigmoidoscopy, rectal biopsy and barium enema study. Colonoscopy has been used, but its role has yet to be defined. In a case of small-bowel steatorrhea or diarrhea quantitative chemical estimation of the daily output of stool fat is useful, and to this investigation is added a small-bowel radiograph series and, if the radiographic findings are abnormal, small-bowel biopsy. Other investigations for small-bowel disease may include the breath test with carbon-14-labelled glycocholic acid, the lactose tolerance test, duodenal aspiration for giardiasis, analysis of serum immunoglobulins and, on occasion, isolation of vasoactive intestinal polypeptide hormone (which may aid the diagnosis of functioning tumours of the pancreas or small bowel). Investigations for pancreatic steatorrhea include abdominal radiography, performance of the secretin test and testing of the response to pancreatic replacement therapy. In some patients it may be useful to use endoscopic retrograde cholangiopancreatography to differentiate pancreatic carcinoma and chronic pancreatitis.", "contents": "Symposium on diarrhea. 3. Investigation of chronic diarrhea. The practical approach to the investigation of diarrhea must be logical and based on anatomic considerations. The site of the underlying disorder may be determined by the clinical picture, and the logic of investigation will be influenced by the history. Important specific investigation in a case of colonic diarrhea include a careful rectal examination, stool inspection, sigmoidoscopy, rectal biopsy and barium enema study. Colonoscopy has been used, but its role has yet to be defined. In a case of small-bowel steatorrhea or diarrhea quantitative chemical estimation of the daily output of stool fat is useful, and to this investigation is added a small-bowel radiograph series and, if the radiographic findings are abnormal, small-bowel biopsy. Other investigations for small-bowel disease may include the breath test with carbon-14-labelled glycocholic acid, the lactose tolerance test, duodenal aspiration for giardiasis, analysis of serum immunoglobulins and, on occasion, isolation of vasoactive intestinal polypeptide hormone (which may aid the diagnosis of functioning tumours of the pancreas or small bowel). Investigations for pancreatic steatorrhea include abdominal radiography, performance of the secretin test and testing of the response to pancreatic replacement therapy. In some patients it may be useful to use endoscopic retrograde cholangiopancreatography to differentiate pancreatic carcinoma and chronic pancreatitis."}
{"id": "PMID:191174", "title": "Changes in peroxisomes in preneoplastic liver of rats induced by 3'-methyl-4-dimethylaminoazobenzene.", "content": "Histochemical investigations used the 3,3'-diaminobenzidine reaction to demonstrate the catalase activity and thus variations in numbers of peroxisomes, and electron microscopic examinations were made of hyperplastic liver lesions in rats fed 0.06%3'-methyl-4-dimethylaminoazobenzene. At the 10th week of carcinogen feeding, hyperplastic lesions (hyperplastic foci, areas, and nodules) appeared and advanced to further stages. Most of the foci and some of the areas and nodules showed very low catalase activity and, correspondingly, a small number of peroxisomes. When rats were administered ethyl-alpha-p-chlorophenoxyisobutyrate, most of the foci, areas, and nodules showed a moderate increase in catalase activity and in peroxisome number. Hyperplastic foci seemed to grow larger with time to form hyperplastic areas and/or nodules, mostly accompanying maturation as well as proliferation of the hepatocytes involved. Maturation is well characterized by an increase in the endogenous level of catalase and in the number of peroxisomes, as well as by an enhancement of the responsiveness to ethyl-alpha-p-chlorophenoxyisobutyrate. However, there was a small proportion of lesions in which all cells or some cells did not mature and thus were considered persistently altered. It is suggested that these altered cells serve mainly as intimate precursors of hepatomas.", "contents": "Changes in peroxisomes in preneoplastic liver of rats induced by 3'-methyl-4-dimethylaminoazobenzene. Histochemical investigations used the 3,3'-diaminobenzidine reaction to demonstrate the catalase activity and thus variations in numbers of peroxisomes, and electron microscopic examinations were made of hyperplastic liver lesions in rats fed 0.06%3'-methyl-4-dimethylaminoazobenzene. At the 10th week of carcinogen feeding, hyperplastic lesions (hyperplastic foci, areas, and nodules) appeared and advanced to further stages. Most of the foci and some of the areas and nodules showed very low catalase activity and, correspondingly, a small number of peroxisomes. When rats were administered ethyl-alpha-p-chlorophenoxyisobutyrate, most of the foci, areas, and nodules showed a moderate increase in catalase activity and in peroxisome number. Hyperplastic foci seemed to grow larger with time to form hyperplastic areas and/or nodules, mostly accompanying maturation as well as proliferation of the hepatocytes involved. Maturation is well characterized by an increase in the endogenous level of catalase and in the number of peroxisomes, as well as by an enhancement of the responsiveness to ethyl-alpha-p-chlorophenoxyisobutyrate. However, there was a small proportion of lesions in which all cells or some cells did not mature and thus were considered persistently altered. It is suggested that these altered cells serve mainly as intimate precursors of hepatomas."}
{"id": "PMID:191175", "title": "Metabolism of estrogens in hepatomas of different growth rates.", "content": "The activity of estrogen 16alpha-hydroxylase was measured for nine Morris hepatomas of different growth rates and host livers. Activity was measured in the microsomal fraction of the cell (100,000 X g). In the spectrum of hepatomas studied, 16alpha-hydroxylase activity was significantly decreased in parallel with the increase in hepatoma growth rate. The decrease in enzymic activity ranged from 16 to 19% for the slow-growing tumors (Hepatomas 44, 28A, and 9633), 2 to 9% for the intermediate-growing tumors (Hepatomas 38B, 7795, and 5123A), and 0% for the fast-growing tumors (Hepatomas 7288C, 7777, and 42A). Estrogen 16alpha-hydroxylase activity of the liver of tumor-bearing rats differed from that of liver of healthy animals. There was a decrease in enzymic activity ranging from 66% to 90% of normal control rats. The activity level of the host liver did not correlate with tumor growth rate. Stimulation of 16alpha-hydroxylase with phenobarbital showed a 4-fold increase in activity in normal liver and only a 2- to 3-fold increase in host livers. The slow- and intermediate-growing hepatomas showed a 1.2-to 1.4-fold increase in enzyme activity, and no activity or stimulation in the fast-growing hepatomas was observed.", "contents": "Metabolism of estrogens in hepatomas of different growth rates. The activity of estrogen 16alpha-hydroxylase was measured for nine Morris hepatomas of different growth rates and host livers. Activity was measured in the microsomal fraction of the cell (100,000 X g). In the spectrum of hepatomas studied, 16alpha-hydroxylase activity was significantly decreased in parallel with the increase in hepatoma growth rate. The decrease in enzymic activity ranged from 16 to 19% for the slow-growing tumors (Hepatomas 44, 28A, and 9633), 2 to 9% for the intermediate-growing tumors (Hepatomas 38B, 7795, and 5123A), and 0% for the fast-growing tumors (Hepatomas 7288C, 7777, and 42A). Estrogen 16alpha-hydroxylase activity of the liver of tumor-bearing rats differed from that of liver of healthy animals. There was a decrease in enzymic activity ranging from 66% to 90% of normal control rats. The activity level of the host liver did not correlate with tumor growth rate. Stimulation of 16alpha-hydroxylase with phenobarbital showed a 4-fold increase in activity in normal liver and only a 2- to 3-fold increase in host livers. The slow- and intermediate-growing hepatomas showed a 1.2-to 1.4-fold increase in enzyme activity, and no activity or stimulation in the fast-growing hepatomas was observed."}
{"id": "PMID:191176", "title": "Adenosine triphosphatases as histochemical markers for the cell of origin in experimental mammary carcinoma.", "content": "Different adenosine triphosphatase (ATPase) activities were detected at an ultrastructural level in order to differentiate epithelial and myoepithelial cells in normal and neoplastic mouse mammary tissues. Mg2+ dependent and Na+-K+-dependent ATPase activities were studied in: BALB/c mouse mammary gland; a BALB/c carcinoma from a transplantable D2 hyperplastic nodule; a stable cell line, MCF-8, derived from the BALB/c carcinoma; and a BALB/c scirrhous-like carcinoma induced by MCF-8 cell inoculation. Mg2+-dependent ATPase was detected in the plasma membranes of the normal mouse mammary epithelial cells, the epithelial component of the BALB/c carcinoma, the MCF-8 cells in culture, and the atypical epithelial component of the scirrhous-like carcinoma. Na+-K+-dependent and Mg2+-dependent ATPase were localized in the plasma membranes of the myoepithelial cells of the normal mammary gland and the BALB/c carcinoma. The results from these histochemical studies established that the cell of origin in both the BALB/c carcinoma and the scirrhous-like carcinoma was the mammary epithelial rather than the myoepithelial cells. Furthermore, these results indicated that the MCF-8 cell line was derived from the epithelial component of the primary BALB/c carcinoma. These conclusions, which were based on histochemical study, were supported by the presence of intracisternal type A viral particles in the epithelial cells of the primary BALB/c carcinoma, the MCF-8 cells in culture, and the epithelial cells of the scirrhous-like carcinoma. Thus, the enzymatic markers were specific for cell type and remained unchanged by the process of cell transformation.", "contents": "Adenosine triphosphatases as histochemical markers for the cell of origin in experimental mammary carcinoma. Different adenosine triphosphatase (ATPase) activities were detected at an ultrastructural level in order to differentiate epithelial and myoepithelial cells in normal and neoplastic mouse mammary tissues. Mg2+ dependent and Na+-K+-dependent ATPase activities were studied in: BALB/c mouse mammary gland; a BALB/c carcinoma from a transplantable D2 hyperplastic nodule; a stable cell line, MCF-8, derived from the BALB/c carcinoma; and a BALB/c scirrhous-like carcinoma induced by MCF-8 cell inoculation. Mg2+-dependent ATPase was detected in the plasma membranes of the normal mouse mammary epithelial cells, the epithelial component of the BALB/c carcinoma, the MCF-8 cells in culture, and the atypical epithelial component of the scirrhous-like carcinoma. Na+-K+-dependent and Mg2+-dependent ATPase were localized in the plasma membranes of the myoepithelial cells of the normal mammary gland and the BALB/c carcinoma. The results from these histochemical studies established that the cell of origin in both the BALB/c carcinoma and the scirrhous-like carcinoma was the mammary epithelial rather than the myoepithelial cells. Furthermore, these results indicated that the MCF-8 cell line was derived from the epithelial component of the primary BALB/c carcinoma. These conclusions, which were based on histochemical study, were supported by the presence of intracisternal type A viral particles in the epithelial cells of the primary BALB/c carcinoma, the MCF-8 cells in culture, and the epithelial cells of the scirrhous-like carcinoma. Thus, the enzymatic markers were specific for cell type and remained unchanged by the process of cell transformation."}
{"id": "PMID:191177", "title": "Light-induced mutagenicity of neutral red (3-amino-7-dimethylamino-2-methylphenazine hydrochloride).", "content": "Illumination of Salmonella typhimurium in the presence of neutral red (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) results in mutations of the base substitution type.", "contents": "Light-induced mutagenicity of neutral red (3-amino-7-dimethylamino-2-methylphenazine hydrochloride). Illumination of Salmonella typhimurium in the presence of neutral red (3-amino-7-dimethylamino-2-methylphenazine hydrochloride) results in mutations of the base substitution type."}
{"id": "PMID:191178", "title": "Changes in leucine aminotransferase isozymes by viral transformation and its correlation with the isozyme changes occurring during differentiation.", "content": "The isozyme pattern of leucine aminotransferase (EC 2.6.1.6) in various cell lines and their viral-transformed derivatives were examined. The Wistar 3C rat liver cell line was found to contain only isozyme I, while its simian virus 40-transformed counterpart had isozyme III in addition to isozyme I. A spontaneously transformed late passage clone of these liver cells was also found to have acquired isozyme III. Polyoma virus-transformed baby hamster kidney cells were also found to contain a greater predominance of isozyme III than their normal untransformed counterpart. Examination of the isozymes in a cloned normal rat kidney cell line transformed by a mutant of Rous sarcoma virus which is temeprature-sensitive for transformation indicated that, in fact, such an isozyme change does correlate with transformation. When grown at 36 degrees these cells contained predominantly isozyme III; however, upon reacquiring normal morphology and lowered glucose transport activity when grown at 40 degrees, their isozyme pattern was now found to be changed and consisted predominantly of isozyme I, as is found in normal adult rat kidney tissue. Isozyme III was found to be present in neonatal kidney tissue of the rat and hamster, and its predominance in the virus-transformed normal rat and baby hamster kidney cells was interpreted as indicative of the dedifferentiation of these cells upon viral transformation. A similar change of the isozyme pattern of leucine aminotransferase in chicken embryos during their development was observed, such that in 5-day-old embryos Form III was predominant, while in the more mature differentiated chicken embryo of Day 17, Form I was predominant.", "contents": "Changes in leucine aminotransferase isozymes by viral transformation and its correlation with the isozyme changes occurring during differentiation. The isozyme pattern of leucine aminotransferase (EC 2.6.1.6) in various cell lines and their viral-transformed derivatives were examined. The Wistar 3C rat liver cell line was found to contain only isozyme I, while its simian virus 40-transformed counterpart had isozyme III in addition to isozyme I. A spontaneously transformed late passage clone of these liver cells was also found to have acquired isozyme III. Polyoma virus-transformed baby hamster kidney cells were also found to contain a greater predominance of isozyme III than their normal untransformed counterpart. Examination of the isozymes in a cloned normal rat kidney cell line transformed by a mutant of Rous sarcoma virus which is temeprature-sensitive for transformation indicated that, in fact, such an isozyme change does correlate with transformation. When grown at 36 degrees these cells contained predominantly isozyme III; however, upon reacquiring normal morphology and lowered glucose transport activity when grown at 40 degrees, their isozyme pattern was now found to be changed and consisted predominantly of isozyme I, as is found in normal adult rat kidney tissue. Isozyme III was found to be present in neonatal kidney tissue of the rat and hamster, and its predominance in the virus-transformed normal rat and baby hamster kidney cells was interpreted as indicative of the dedifferentiation of these cells upon viral transformation. A similar change of the isozyme pattern of leucine aminotransferase in chicken embryos during their development was observed, such that in 5-day-old embryos Form III was predominant, while in the more mature differentiated chicken embryo of Day 17, Form I was predominant."}
{"id": "PMID:191179", "title": "Demonstration of different glycosylated antigens in C-type virus-transformed and infected rat cells by antiserum to murine leukemia virus.", "content": "[3H]Glucosamine labeling of untransformed cells, C-type virus-transformed cells, and virus-infected cells and subsequent analysis by polyacrylamide gel electrophoresis and fluorography permitted the detection of a Pronase-sensitive macromolecular labeling that appeared in about eight regions of radioactivity in every case. Reactions of cell extracts with antiserum to Tween-ether-disrupted purified murine leukemia virus revealed, in most transformed cells, two components with a mobility of about 100,000 daltons, whereas C-type virus-infected cells revealed their radioactivity mainly in a region nearer to that of the major viral glycoprotein at about 69,000 daltons. No comparable components were apparent from the reaction of transformed or infected extracts with preimmune serum or from the reaction of untransformed uninfected cells and immune serum.", "contents": "Demonstration of different glycosylated antigens in C-type virus-transformed and infected rat cells by antiserum to murine leukemia virus. [3H]Glucosamine labeling of untransformed cells, C-type virus-transformed cells, and virus-infected cells and subsequent analysis by polyacrylamide gel electrophoresis and fluorography permitted the detection of a Pronase-sensitive macromolecular labeling that appeared in about eight regions of radioactivity in every case. Reactions of cell extracts with antiserum to Tween-ether-disrupted purified murine leukemia virus revealed, in most transformed cells, two components with a mobility of about 100,000 daltons, whereas C-type virus-infected cells revealed their radioactivity mainly in a region nearer to that of the major viral glycoprotein at about 69,000 daltons. No comparable components were apparent from the reaction of transformed or infected extracts with preimmune serum or from the reaction of untransformed uninfected cells and immune serum."}
{"id": "PMID:191180", "title": "Continued presence of similar transformation-associated antigens related to murine oncornavirus proteins in -ransformed cells, morphological revertants, and cells restricted in the expression of transformation.", "content": "The possible alteration of transformation-related antigens in cells that revert to a normal phenotype but that continue to retain the viral genome, has been investigated in [3H]glucosamine-labeled extracts of rat cells exhibiting a reversible temperature-dependent restriction in the expression of transformation and in a comparison of a morphologically altered mouse cell transformed by the Kirsten sarcoma virus with a flat revertant mouse cell derived from the morphologically transformed cells. With the use of normal goat serum in the presence of dibutyryl cyclic 3':5'-adenosine monophosphate, some differences became obvious in the rat cells restricted in the expression of transformation. However, use of specific antiserum to murine leukemia virus revealed in every case the presence of major components that exhibited an electrophoretic mobility corresponding to about 100,000 daltons both in the parent and revertant mouse cells and in the rat cells exhibiting either untransformed or transformed growth properties. The glycoprotein components detected only by the immune serum may represent a cellular macromolecule antigenically related to an interspecies C-type viral species whose concentration is increased in transformed cells.", "contents": "Continued presence of similar transformation-associated antigens related to murine oncornavirus proteins in -ransformed cells, morphological revertants, and cells restricted in the expression of transformation. The possible alteration of transformation-related antigens in cells that revert to a normal phenotype but that continue to retain the viral genome, has been investigated in [3H]glucosamine-labeled extracts of rat cells exhibiting a reversible temperature-dependent restriction in the expression of transformation and in a comparison of a morphologically altered mouse cell transformed by the Kirsten sarcoma virus with a flat revertant mouse cell derived from the morphologically transformed cells. With the use of normal goat serum in the presence of dibutyryl cyclic 3':5'-adenosine monophosphate, some differences became obvious in the rat cells restricted in the expression of transformation. However, use of specific antiserum to murine leukemia virus revealed in every case the presence of major components that exhibited an electrophoretic mobility corresponding to about 100,000 daltons both in the parent and revertant mouse cells and in the rat cells exhibiting either untransformed or transformed growth properties. The glycoprotein components detected only by the immune serum may represent a cellular macromolecule antigenically related to an interspecies C-type viral species whose concentration is increased in transformed cells."}
{"id": "PMID:191181", "title": "Casein and alpha-lactalbumin messenger RNA in experimental breast cancer.", "content": "A transplantable rat mammary carcinoma (R3230AC) was previously shown to contain prolactin receptors. Our objective was to determine whether these receptors were functional by measuring specific markers of prolactin action: casein and alpha-lactalbumin (alphaLA) messenger RNA's (mRNA's). Total RNA exacts were translated in a wheat germ cell-free system. Newly synthesized 3H-casein and 3H-alphaLA were separately precipitated with specific antibodies and identified by their mobilities on sodium dodecyl sulfate-acrylamide gels and by competition with nonradioactive casein and alphaLA. Casein and alphaLA mRNA's were both present in unstimulated tumors grown in virgin rats. Casein mRNA but not alphaLA mRNA was markedly stimulated by injections of exogenous ovine prolactin or perphenazine, an agent that stimulates endogenous prolactin. This response was selective in that total mRNA was not significantly altered by prolactin.", "contents": "Casein and alpha-lactalbumin messenger RNA in experimental breast cancer. A transplantable rat mammary carcinoma (R3230AC) was previously shown to contain prolactin receptors. Our objective was to determine whether these receptors were functional by measuring specific markers of prolactin action: casein and alpha-lactalbumin (alphaLA) messenger RNA's (mRNA's). Total RNA exacts were translated in a wheat germ cell-free system. Newly synthesized 3H-casein and 3H-alphaLA were separately precipitated with specific antibodies and identified by their mobilities on sodium dodecyl sulfate-acrylamide gels and by competition with nonradioactive casein and alphaLA. Casein and alphaLA mRNA's were both present in unstimulated tumors grown in virgin rats. Casein mRNA but not alphaLA mRNA was markedly stimulated by injections of exogenous ovine prolactin or perphenazine, an agent that stimulates endogenous prolactin. This response was selective in that total mRNA was not significantly altered by prolactin."}
{"id": "PMID:191182", "title": "Predominant role of prolactin in stimulating the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor.", "content": "The effect of prolactin in supporting the growth of 7, 12-dimethylbenz(a)anthracene-induced mammary tumor in adult female Sprague-Dawley rats was investigated when estrogen receptors were blocked by the nonsteroidal antiestrogen, Tamoxifen, ICI 46,474. Following an oophorectomy-induced remission, perphenazine, which stimulates endogenous prolactin release, was able to restore tumor growth whether or not Tamoxifen was added. A second course of perphenazine treatment, instituted after the tumors were allowed to shrink, was again effective in stimulating tumor growth. After a regression in tumor size induced by oophorectomy and daily administration of Tamoxifen, perphenazine was able to restore original tumor size despite continued treatment with Tamoxifen. In intact rats, after regression was obtained by daily administration of Tamoxifen and the prolactin inhibitor, lergotrile mesylate, perphenazine induced tumor growth when the latter was discontinued, even though Tamoxifen was continued for 50 days. Estrogen receptors measured at the time of maximum stimulation by perphenazine were undetectable. On the other hand, estradiol did not stimulate tumor growth when serum prolactin was depressed to undetectable levels by lergotrile. These results indicate that prolactin supports the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor and that estrogen receptors are not required under these conditions.", "contents": "Predominant role of prolactin in stimulating the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor. The effect of prolactin in supporting the growth of 7, 12-dimethylbenz(a)anthracene-induced mammary tumor in adult female Sprague-Dawley rats was investigated when estrogen receptors were blocked by the nonsteroidal antiestrogen, Tamoxifen, ICI 46,474. Following an oophorectomy-induced remission, perphenazine, which stimulates endogenous prolactin release, was able to restore tumor growth whether or not Tamoxifen was added. A second course of perphenazine treatment, instituted after the tumors were allowed to shrink, was again effective in stimulating tumor growth. After a regression in tumor size induced by oophorectomy and daily administration of Tamoxifen, perphenazine was able to restore original tumor size despite continued treatment with Tamoxifen. In intact rats, after regression was obtained by daily administration of Tamoxifen and the prolactin inhibitor, lergotrile mesylate, perphenazine induced tumor growth when the latter was discontinued, even though Tamoxifen was continued for 50 days. Estrogen receptors measured at the time of maximum stimulation by perphenazine were undetectable. On the other hand, estradiol did not stimulate tumor growth when serum prolactin was depressed to undetectable levels by lergotrile. These results indicate that prolactin supports the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor and that estrogen receptors are not required under these conditions."}
{"id": "PMID:191183", "title": "Prolactin and murine mammary tumorigenesis: a review.", "content": "It is unequivocal that prolactin is an influential hormone in murine mammary tumorigenesis. The Berenblum hypothesis (7), a well-known theoretical model of tumorigenesis that depicts this oncogenic process as a two-step mechanism, i.e., initiation and promotion, is a conceptual scheme in which the action of prolactin in mammary tumorigenesis may be understood. According to this conceptual model, prolactin would participate in both the initiation and promotion steps of mammary tumorigenesis, In the initiation phase, variations in prolactin secretion appear to influence the metabolism of the mammary epithelium, so that the epithelium would be either more receptive to or refractory to an initiating agent (e.g., chemical carcinogen, physical carcinogens, oncogenic viruses, ets.) i.e., a permissive action. In the promotion phase, prolactin may act as either a promoter or an antipromoter of the \"transformed\" mammary epithelium. In promotion, the hormone may either directly or indirectly (via the ovary) stimulate mitotic activity of the \"transformed\" epithelium. In antipromotion the hormone, in the presence of requisite hormones (e.g., glucocorticoids), may synergistically induce differentiation (e.g., lactation) in the \"transformed\" epithelium. A tumor would result in the former (promotion) but not in the latter (antipromotion) case. Whether or not prolactin is significantly influential in human breast tumorigenesis remains to be determined. This is an extremely important area of research which is justifiably receiving increased attention. For if prolactin can be shown to influence human breast epithelium in a manner similar to its effect on rodent mammary tissue, then prophylactic and/of chemotherapeutic control of human breast tumorigenesis may be feasible by appropriate drug-mediated prolactin suppression.", "contents": "Prolactin and murine mammary tumorigenesis: a review. It is unequivocal that prolactin is an influential hormone in murine mammary tumorigenesis. The Berenblum hypothesis (7), a well-known theoretical model of tumorigenesis that depicts this oncogenic process as a two-step mechanism, i.e., initiation and promotion, is a conceptual scheme in which the action of prolactin in mammary tumorigenesis may be understood. According to this conceptual model, prolactin would participate in both the initiation and promotion steps of mammary tumorigenesis, In the initiation phase, variations in prolactin secretion appear to influence the metabolism of the mammary epithelium, so that the epithelium would be either more receptive to or refractory to an initiating agent (e.g., chemical carcinogen, physical carcinogens, oncogenic viruses, ets.) i.e., a permissive action. In the promotion phase, prolactin may act as either a promoter or an antipromoter of the \"transformed\" mammary epithelium. In promotion, the hormone may either directly or indirectly (via the ovary) stimulate mitotic activity of the \"transformed\" epithelium. In antipromotion the hormone, in the presence of requisite hormones (e.g., glucocorticoids), may synergistically induce differentiation (e.g., lactation) in the \"transformed\" epithelium. A tumor would result in the former (promotion) but not in the latter (antipromotion) case. Whether or not prolactin is significantly influential in human breast tumorigenesis remains to be determined. This is an extremely important area of research which is justifiably receiving increased attention. For if prolactin can be shown to influence human breast epithelium in a manner similar to its effect on rodent mammary tissue, then prophylactic and/of chemotherapeutic control of human breast tumorigenesis may be feasible by appropriate drug-mediated prolactin suppression."}
{"id": "PMID:191184", "title": "The chromosome analysis and susceptibility to transformation by Simian Virus 40 of fibroblasts from ataxia-telangiectasia.", "content": "Chromosome analyses are reported for 14 lines of fibro-blasts derived from 8 ataxia-telangiectasia (ATT) patients and for 14 lines of control cells. An elevated incidence of chromosome damage including gaps and breaks, rings, dicentrics and fragments, and chromosome figures has been found to occur in ATT cells. Similar abnormalities present in different cell lines suggest that common break points occur in ATT fibroblast chromosomes. The SV40 virus transformation rates found for ATT cells lie within the range found for normal cells, and there is no direct correlation between the degree of chromosome damage exhibited by any ATT cell line and its transformation rate with SV40.", "contents": "The chromosome analysis and susceptibility to transformation by Simian Virus 40 of fibroblasts from ataxia-telangiectasia. Chromosome analyses are reported for 14 lines of fibro-blasts derived from 8 ataxia-telangiectasia (ATT) patients and for 14 lines of control cells. An elevated incidence of chromosome damage including gaps and breaks, rings, dicentrics and fragments, and chromosome figures has been found to occur in ATT cells. Similar abnormalities present in different cell lines suggest that common break points occur in ATT fibroblast chromosomes. The SV40 virus transformation rates found for ATT cells lie within the range found for normal cells, and there is no direct correlation between the degree of chromosome damage exhibited by any ATT cell line and its transformation rate with SV40."}
{"id": "PMID:191185", "title": "Therapeutic use of tamoxifen in advanced breast cancer: correlation with biochemical parameters.", "content": "Tamoxifen (NSC-180973; ICI-46474) can provide palliation to patients with advanced breast cancer whose tumors contain estrogen-binding proteins (EBP). The drug is most effective in patients with bone metastasis and minimal prior therapy. In the present study, 72 patients with advanced breast cancer were evaluated for their response to oral tamoxifen therapy administered at a dose of 20 mg twice daily. Twenty-eight of 72 patients (38%) demonstrated objective responses to tamoxifen therapy. For patients with a positive EBP and no prior chemotherapy, eight of 11 (74%) responded. No patient possessing a tumor negative for EBP achieved a remission. Patients with tumors that possessed normal arylsulfatase B and glucose-6-phosphate dehydrogenase enzyme activities responded most favorably to tamoxifen therapy. These results demonstrate that tamoxifen is effective in the treatment of patients with advanced breast cancer, and EBP and specific enzymes might be useful in selecting the patients for hormone manipulation.", "contents": "Therapeutic use of tamoxifen in advanced breast cancer: correlation with biochemical parameters. Tamoxifen (NSC-180973; ICI-46474) can provide palliation to patients with advanced breast cancer whose tumors contain estrogen-binding proteins (EBP). The drug is most effective in patients with bone metastasis and minimal prior therapy. In the present study, 72 patients with advanced breast cancer were evaluated for their response to oral tamoxifen therapy administered at a dose of 20 mg twice daily. Twenty-eight of 72 patients (38%) demonstrated objective responses to tamoxifen therapy. For patients with a positive EBP and no prior chemotherapy, eight of 11 (74%) responded. No patient possessing a tumor negative for EBP achieved a remission. Patients with tumors that possessed normal arylsulfatase B and glucose-6-phosphate dehydrogenase enzyme activities responded most favorably to tamoxifen therapy. These results demonstrate that tamoxifen is effective in the treatment of patients with advanced breast cancer, and EBP and specific enzymes might be useful in selecting the patients for hormone manipulation."}
{"id": "PMID:191189", "title": "Inhibitors of hypoxanthine metabolism in Ehrlich ascites tumor cells in vitro.", "content": "One hundred and sixty-one purine analogs and derivatives were tested for their ability to inhibit ten parameters of purine metabolism in Ehrlich ascites tumor cells incubated in vitro with radioactive hypoxanthine. Sixty-seven compounds were inhibitory against at least one parameter and 30 were inhibitory against two or more.", "contents": "Inhibitors of hypoxanthine metabolism in Ehrlich ascites tumor cells in vitro. One hundred and sixty-one purine analogs and derivatives were tested for their ability to inhibit ten parameters of purine metabolism in Ehrlich ascites tumor cells incubated in vitro with radioactive hypoxanthine. Sixty-seven compounds were inhibitory against at least one parameter and 30 were inhibitory against two or more."}
{"id": "PMID:191190", "title": "Antitumor activity of 1,2-bis diazoacetyl ethane.", "content": "1,2-Bis diazoacetyl ethane (diazane) was selected for a detailed study as the most active compound in a large group of mono- and bi-functional diazoketones subjected to screening. In this paper data on the toxicity and cumulative and antitumor effects of diazane are reported. Diazane markedly inhibits the growth of certain experimental tumors and increases the mean survival time of animals with leukemias, even after a single injection. The drug is characterized by a high level of accumulation in the body.", "contents": "Antitumor activity of 1,2-bis diazoacetyl ethane. 1,2-Bis diazoacetyl ethane (diazane) was selected for a detailed study as the most active compound in a large group of mono- and bi-functional diazoketones subjected to screening. In this paper data on the toxicity and cumulative and antitumor effects of diazane are reported. Diazane markedly inhibits the growth of certain experimental tumors and increases the mean survival time of animals with leukemias, even after a single injection. The drug is characterized by a high level of accumulation in the body."}
{"id": "PMID:191191", "title": "Survival and cycle-progression delay of cultured human lymphoma cells treated with 1-propanol, 3,3'-iminodi-, dimethanesulfonate (ester), hydrochloride (Yoshi 864).", "content": "Asynchronous human lymphoma cells treated for 1 hour with increasing concentrations of 1-propanol, 3,3'-iminodi-, dimethanesulfonate (ester), hydrochloride (Yoshi 864) revealed a shouldered survival curve typical of the effects of alkylating agents and of ionizing radiation on this cell line. Yoshi 864 was unstable under the conditions of treatment, its killing effect being reduced by 50% after only 4 hours. Synchronized cells showed stage-dependent sensitivity: early-S, late-G2, and late-G1 phases were the most sensitive while mid- and late-S and early-G2 phases were relatively insensitive. Yoshi 864 induced a concentration- and incubation time-dependent delay in the transit of asynchronous cells through G2 phase, with maximum accumulation values obtained after 12 hours of incubation with 100 mug/ml. This effect was largely reversible and no further kinetic changes were noted in the progeny of treated cells. Incubation of synchronized cells for 1 hour with 100 mug/ml demonstrated a block in G2, the manifestation of which during the lifespan of the treated cell or in its immediate progeny was cell-cycle dependent. Thus, cells treated in G1, early-, and mid-S phases showed a delay in the subsequent G2 phase while cells treated in late S and in G2 manifested this effect in the G2 phase of the immediate progeny. There was no correlation between this blocking effect in G2 with cell survival assessed by colony formation. Yoshi 864, although a rather inefficient killing drug, may represent a useful chemical synchronizing agent.", "contents": "Survival and cycle-progression delay of cultured human lymphoma cells treated with 1-propanol, 3,3'-iminodi-, dimethanesulfonate (ester), hydrochloride (Yoshi 864). Asynchronous human lymphoma cells treated for 1 hour with increasing concentrations of 1-propanol, 3,3'-iminodi-, dimethanesulfonate (ester), hydrochloride (Yoshi 864) revealed a shouldered survival curve typical of the effects of alkylating agents and of ionizing radiation on this cell line. Yoshi 864 was unstable under the conditions of treatment, its killing effect being reduced by 50% after only 4 hours. Synchronized cells showed stage-dependent sensitivity: early-S, late-G2, and late-G1 phases were the most sensitive while mid- and late-S and early-G2 phases were relatively insensitive. Yoshi 864 induced a concentration- and incubation time-dependent delay in the transit of asynchronous cells through G2 phase, with maximum accumulation values obtained after 12 hours of incubation with 100 mug/ml. This effect was largely reversible and no further kinetic changes were noted in the progeny of treated cells. Incubation of synchronized cells for 1 hour with 100 mug/ml demonstrated a block in G2, the manifestation of which during the lifespan of the treated cell or in its immediate progeny was cell-cycle dependent. Thus, cells treated in G1, early-, and mid-S phases showed a delay in the subsequent G2 phase while cells treated in late S and in G2 manifested this effect in the G2 phase of the immediate progeny. There was no correlation between this blocking effect in G2 with cell survival assessed by colony formation. Yoshi 864, although a rather inefficient killing drug, may represent a useful chemical synchronizing agent."}
{"id": "PMID:191195", "title": "Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts.", "content": "125I-labeled and ferritin-labeled low density lipoprotein (LDL) were used as visual probes to study the surface distribution of LDL receptors and to examine the mechanism of the endocytosis of this lipoprotein in cultured human fibrobasts. Light microscopic autoradiograms of whole cells incubated with 125I-LDL at 4 degrees C showed that LDL receptors were widely but unevenly distributed over the cell surface. With the electron microscope, we determined that 60-70% of the ferritin-labeled LDL that bound to cells at 4 degrees C was localized over short coated segments of the plasma membrane that accounted for no more than 2% of the total surface area. To study the internalization process, cells were first allowed to bind ferritin-labeled LDL at 4 degrees C and were then warmed to 37 degrees C. Within 10 min, nearly all the surface-bound LDL-ferritin was incorporated into coated endocytic vesicles that were formed by the invagination and pinching-off of the coated membrane regions that contained the receptor-bound LDL. With increasing time at 37 degrees C, these coated vesicles were observed sequentially to migrate through the cytoplasm (1 min), to lose their cytoplasmic coat (2 min), and to fuse with either primary or secondary lysosomes (6 min). The current data indicate that the coated regions of plasma membrane are specialized structures of rapid turnover that function to carry receptor-bound LDL, and perhaps other receptor-bound molecules, into the cell.", "contents": "Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts. 125I-labeled and ferritin-labeled low density lipoprotein (LDL) were used as visual probes to study the surface distribution of LDL receptors and to examine the mechanism of the endocytosis of this lipoprotein in cultured human fibrobasts. Light microscopic autoradiograms of whole cells incubated with 125I-LDL at 4 degrees C showed that LDL receptors were widely but unevenly distributed over the cell surface. With the electron microscope, we determined that 60-70% of the ferritin-labeled LDL that bound to cells at 4 degrees C was localized over short coated segments of the plasma membrane that accounted for no more than 2% of the total surface area. To study the internalization process, cells were first allowed to bind ferritin-labeled LDL at 4 degrees C and were then warmed to 37 degrees C. Within 10 min, nearly all the surface-bound LDL-ferritin was incorporated into coated endocytic vesicles that were formed by the invagination and pinching-off of the coated membrane regions that contained the receptor-bound LDL. With increasing time at 37 degrees C, these coated vesicles were observed sequentially to migrate through the cytoplasm (1 min), to lose their cytoplasmic coat (2 min), and to fuse with either primary or secondary lysosomes (6 min). The current data indicate that the coated regions of plasma membrane are specialized structures of rapid turnover that function to carry receptor-bound LDL, and perhaps other receptor-bound molecules, into the cell."}
{"id": "PMID:191196", "title": "Mutations causing charge alterations in regulatory subunits of the cAMP-dependent protein kinase of cultured S49 lymphoma cells.", "content": "Two-dimensional polyacrylamide gel electrophoresis is used to visualize the regulatory subunit of cAMP-dependent protein kinase from cultured S49 mouse lymphoma cells and to demonstrate its in vivo phosphorylation. Regulatory subunits from mutant cells with altered kinases exhibit at least two patterns of charge shifts consistent with substitutions of single amino acids. The direct demonstration of structural alteration of this protein provides strong evidence for structural gene mutation in this cultured cell system. While mutant and wild-type gene products co-exist in the mutant cells, there is apparently preferential expression and phosphorylation of mutant subunit in these heterozygotes.", "contents": "Mutations causing charge alterations in regulatory subunits of the cAMP-dependent protein kinase of cultured S49 lymphoma cells. Two-dimensional polyacrylamide gel electrophoresis is used to visualize the regulatory subunit of cAMP-dependent protein kinase from cultured S49 mouse lymphoma cells and to demonstrate its in vivo phosphorylation. Regulatory subunits from mutant cells with altered kinases exhibit at least two patterns of charge shifts consistent with substitutions of single amino acids. The direct demonstration of structural alteration of this protein provides strong evidence for structural gene mutation in this cultured cell system. While mutant and wild-type gene products co-exist in the mutant cells, there is apparently preferential expression and phosphorylation of mutant subunit in these heterozygotes."}
{"id": "PMID:191197", "title": "Loss of Fv-1 restriction in Balb/3T3 cells following infection with a single N tropic murine leukemia virus particle.", "content": "The ability of various murine leukemia viruses (MuLVs) to replicate in mouse cells exhibiting Fv-1 restriction was analyzed by quantitative dose-response assays. In particular, the effect of infection with N, B, or NB tropic MuLVs on Fv-1b restriction in Balb/3T3 cells was measured with an infection center technique in which pseudotypes of murine sarcoma virus (MSV), which have been shown to exhibit Fv-1 dependence of expression, were used to quantitate the degree of restriction. The resulting dose-response curves indicate that productive infection of a single Balb/3T3 cell with N tropic MSV requires co-infection with two MuLV particles. These two MuLV particles are functionally distinguishable. One of them must be N tropic and must be added less than 18 hr after infection with N tropic MSV. The second MuLV particle, on the other hand, need not be N tropic and may be added at any time. Balb/3T3 cultures infected with sufficient N tropic MuLV become fully permissive to transformation by N tropic MSV and to productive infection by N tropic MuLV. This effect, termed \"abrogation\" of Fv-1 restriction, results from infection of a Balb/3T3 cell with a single N tropic MuLV particle, but apparently occurs without viral replication. It seems probable that a requirement for abrogation of Fv-1b restriction by a single infectious particle of N tropic MuLV, which does not itself replicate, is responsible for the two-hit dose-response relationship observed in infectivity titrations of N tropic MuLV in Balb/3T3 cells. The requirements that N tropic MuLV be added within a specified time period with regard to N tropic MSV in order for abrogation to occur suggests that in the absence of N tropic MuLV, the cellular Fv-1b restriction mechanism inactivates N tropic MSV by 9 hr after infection.", "contents": "Loss of Fv-1 restriction in Balb/3T3 cells following infection with a single N tropic murine leukemia virus particle. The ability of various murine leukemia viruses (MuLVs) to replicate in mouse cells exhibiting Fv-1 restriction was analyzed by quantitative dose-response assays. In particular, the effect of infection with N, B, or NB tropic MuLVs on Fv-1b restriction in Balb/3T3 cells was measured with an infection center technique in which pseudotypes of murine sarcoma virus (MSV), which have been shown to exhibit Fv-1 dependence of expression, were used to quantitate the degree of restriction. The resulting dose-response curves indicate that productive infection of a single Balb/3T3 cell with N tropic MSV requires co-infection with two MuLV particles. These two MuLV particles are functionally distinguishable. One of them must be N tropic and must be added less than 18 hr after infection with N tropic MSV. The second MuLV particle, on the other hand, need not be N tropic and may be added at any time. Balb/3T3 cultures infected with sufficient N tropic MuLV become fully permissive to transformation by N tropic MSV and to productive infection by N tropic MuLV. This effect, termed \"abrogation\" of Fv-1 restriction, results from infection of a Balb/3T3 cell with a single N tropic MuLV particle, but apparently occurs without viral replication. It seems probable that a requirement for abrogation of Fv-1b restriction by a single infectious particle of N tropic MuLV, which does not itself replicate, is responsible for the two-hit dose-response relationship observed in infectivity titrations of N tropic MuLV in Balb/3T3 cells. The requirements that N tropic MuLV be added within a specified time period with regard to N tropic MSV in order for abrogation to occur suggests that in the absence of N tropic MuLV, the cellular Fv-1b restriction mechanism inactivates N tropic MSV by 9 hr after infection."}
{"id": "PMID:191198", "title": "Occurrence of reiterated sequences in an untranslated region of Simian virus 40 DNA determined by nucleotide sequence analysis.", "content": "An earlier report (Subramanian, Dhar, and Weissman, 1977c) presented the nucleotide sequence of Eco RII-G fragment of SV40 DNA, which contains the origin of DNA replication. The nucleotide sequence of Eco RII-N fragment located next to Eco RII-G on the physical map of SV40 DNA is presented in this report. Eco RII-N is found to be a tandem duplication of the last 55 nucleotides of Eco RII-G. This tandem repeat is immediately preceded by two other reiterated sequences occurring within Eco RII-G, one of them being a tandem repeat of 21 nucleotides and the other a nontandem repeat of 10 nucleotides. These repetitive sequences occur in close proximity to the origin of DNA replication which is known to contain other specialized sequences such as a few palindromes (one of which is 27 long and possesses a perfect 2-fold axis of symmetry), one \"true\" palindrome, and a long A/T-rich cluster. The repeats (and the replication origin) occur within an untranslated region of SV40 DNA flanked by (the few) structural genes coding for the \"late\" proteins on the one side and that (those) coding for the \"early\" protein(s) on the other side. The reiterated sequences are comparable in some respects to repetitive sequences occurring in eucaryotic DNAs. Possible biological functions of the repeats are discussed.", "contents": "Occurrence of reiterated sequences in an untranslated region of Simian virus 40 DNA determined by nucleotide sequence analysis. An earlier report (Subramanian, Dhar, and Weissman, 1977c) presented the nucleotide sequence of Eco RII-G fragment of SV40 DNA, which contains the origin of DNA replication. The nucleotide sequence of Eco RII-N fragment located next to Eco RII-G on the physical map of SV40 DNA is presented in this report. Eco RII-N is found to be a tandem duplication of the last 55 nucleotides of Eco RII-G. This tandem repeat is immediately preceded by two other reiterated sequences occurring within Eco RII-G, one of them being a tandem repeat of 21 nucleotides and the other a nontandem repeat of 10 nucleotides. These repetitive sequences occur in close proximity to the origin of DNA replication which is known to contain other specialized sequences such as a few palindromes (one of which is 27 long and possesses a perfect 2-fold axis of symmetry), one \"true\" palindrome, and a long A/T-rich cluster. The repeats (and the replication origin) occur within an untranslated region of SV40 DNA flanked by (the few) structural genes coding for the \"late\" proteins on the one side and that (those) coding for the \"early\" protein(s) on the other side. The reiterated sequences are comparable in some respects to repetitive sequences occurring in eucaryotic DNAs. Possible biological functions of the repeats are discussed."}
{"id": "PMID:191207", "title": "A prospective study of acute viral hepatitis with particular reference to hepatitis A.", "content": "In order to investigate the relationship of hepatitis A antigen to viral hepatitis, a prospective study was carried out on 97 patients admitted to Fairfield Hospital, Melbourne, with suspected viral hepatitis, and 3 of their family contacts. Evidence of infection with hepatitis A virus was obtained by detecting hepatitis A antigen in stools, and/or antibody to it in sera, by immune electron microscopy. Infection with hepatitis B virus was determined by testing for hepatitis B surface antigen and antibody in serum, by solid phase radioimmunoassay. Sixteen patients were found to have diseases other than viral hepatitis and 2 patients (child contacts) suffered no illness. There was clinical and/or biochemical evidence compatible with viral hepatitis in 82 patients, of whom 35 were confirmed as having hepatitis A and 31 as having hepatitis B infections. In the remaining 16 patients there was no evidence of infection with either hepatitis A or B virus. It is possible that some of these patients may have been infected with viral agents as yet unidentified.", "contents": "A prospective study of acute viral hepatitis with particular reference to hepatitis A. In order to investigate the relationship of hepatitis A antigen to viral hepatitis, a prospective study was carried out on 97 patients admitted to Fairfield Hospital, Melbourne, with suspected viral hepatitis, and 3 of their family contacts. Evidence of infection with hepatitis A virus was obtained by detecting hepatitis A antigen in stools, and/or antibody to it in sera, by immune electron microscopy. Infection with hepatitis B virus was determined by testing for hepatitis B surface antigen and antibody in serum, by solid phase radioimmunoassay. Sixteen patients were found to have diseases other than viral hepatitis and 2 patients (child contacts) suffered no illness. There was clinical and/or biochemical evidence compatible with viral hepatitis in 82 patients, of whom 35 were confirmed as having hepatitis A and 31 as having hepatitis B infections. In the remaining 16 patients there was no evidence of infection with either hepatitis A or B virus. It is possible that some of these patients may have been infected with viral agents as yet unidentified."}
{"id": "PMID:191208", "title": "Seroimmunity to polioviruses in an urban population of Italy.", "content": "In a seroepidemiological survey on immunity to polioviruses, carried out in Rome, neutralizing antibodies were titrated on 602 serum samples collected from individuals aged from 6 months to 88 years. The geometric mean titres were 25.24, 25.92, and 18.12 for poliovirus types 1, 2, and 3, respectively. The number of seronegative results for each virus strain was very low (</=1.5%). The immune status of the study population could therefore be considered satisfactory. The distribution of antibody reactivity in different age groups was similar for poliovirus types 1 and 3, while for type 2 a significant difference in titres was found between adults and children.", "contents": "Seroimmunity to polioviruses in an urban population of Italy. In a seroepidemiological survey on immunity to polioviruses, carried out in Rome, neutralizing antibodies were titrated on 602 serum samples collected from individuals aged from 6 months to 88 years. The geometric mean titres were 25.24, 25.92, and 18.12 for poliovirus types 1, 2, and 3, respectively. The number of seronegative results for each virus strain was very low (</=1.5%). The immune status of the study population could therefore be considered satisfactory. The distribution of antibody reactivity in different age groups was similar for poliovirus types 1 and 3, while for type 2 a significant difference in titres was found between adults and children."}
{"id": "PMID:191209", "title": "Poxvirus infection of the baboon (Papio cynocephalus).", "content": "Ten serial passages of monkeypox (MPV), vaccinia, variola, and chimpanzeepox (chimp-9) viruses were performed in baboons (Papio cynocephalus) via skin scarification. Comparisons of clinical and virological results indicate that MPV and vaccinia are very closely related and that variola and chimp-9 viruses are identical. These findings suggest that infections of simians with chimp-9 virus resulted from contact with variola virus, the source of which is still unknown. On the other hand, MPV in monkeys may have resulted from contact with recently vaccinated humans, serial passage through simian hosts resulting in the biological alterations that produced MPV.", "contents": "Poxvirus infection of the baboon (Papio cynocephalus). Ten serial passages of monkeypox (MPV), vaccinia, variola, and chimpanzeepox (chimp-9) viruses were performed in baboons (Papio cynocephalus) via skin scarification. Comparisons of clinical and virological results indicate that MPV and vaccinia are very closely related and that variola and chimp-9 viruses are identical. These findings suggest that infections of simians with chimp-9 virus resulted from contact with variola virus, the source of which is still unknown. On the other hand, MPV in monkeys may have resulted from contact with recently vaccinated humans, serial passage through simian hosts resulting in the biological alterations that produced MPV."}
{"id": "PMID:191210", "title": "[Immunocytological identification of two cell types in the intermediate lobe of the hypophysis of salmonids: presence of ACTH and alpha-MSH].", "content": "The lead-haematoxylin positive cells (PbH+) of the rostral pars distalis react with antibodies anti-1-24 ACTH and anti-17-39 ACTH; the pars intermedia (PI) is composed of two cell categories, but only one is revealed with cyto-immunological techniques and contains ACTH and alpha-MSH in several Salmonid species.", "contents": "[Immunocytological identification of two cell types in the intermediate lobe of the hypophysis of salmonids: presence of ACTH and alpha-MSH]. The lead-haematoxylin positive cells (PbH+) of the rostral pars distalis react with antibodies anti-1-24 ACTH and anti-17-39 ACTH; the pars intermedia (PI) is composed of two cell categories, but only one is revealed with cyto-immunological techniques and contains ACTH and alpha-MSH in several Salmonid species."}
{"id": "PMID:191211", "title": "[Demonstration of a cytosol protein binding cholesterol in the adrenal glands].", "content": "Characterization of a cytosolic protein of adrenal origin that binds cholesterol. Adrenal cytosol contains a thermostable protein which binds cholesterol specifically and non-covalently. The sedimentation coefficient of the complex is close to 3 S. The side chain of the cholesterol molecule is responsible for the binding specificity.", "contents": "[Demonstration of a cytosol protein binding cholesterol in the adrenal glands]. Characterization of a cytosolic protein of adrenal origin that binds cholesterol. Adrenal cytosol contains a thermostable protein which binds cholesterol specifically and non-covalently. The sedimentation coefficient of the complex is close to 3 S. The side chain of the cholesterol molecule is responsible for the binding specificity."}
{"id": "PMID:191212", "title": "Stimulation of cholesterol esterification in rhesus monkey arterial smooth muscle cells.", "content": "The influence of homologous high density lipoprotein (HDL) and low density lipoprotein (LDL) and of whole hypercholesterolemic serum on the esterification of oleic acid and cholesterol was studied in rhesus monkey arterial smooth muscle cells. Whole hypercholesterolemic serum and isolated LDL stimulated cholesterol esterification as much as 10-fold using either cholesterol-1,2-3H or oleate-1-14C as substrate. At the same concentrations of cholesterol, HDL stimulated cholesterol esterification to a lesser extent, to a maximum of 3-fold. Associated with the stimulation of cholesterol esterification by LDL or whole hypercholesterolemic serum was a greater than 10-fold increase in the cholesteryl ester content of the arterial smooth muscle cells. Esterification to cholesterol reached a maximum after 8-12 hours of culture with either hypercholesterolemic serum or LDL. The stimulation of esterification was specific for esterification to cholesterol because there was little change in incorporation of fatty acid into triglycerides and phospholipids. These studies provide further evidence that a major consequence of the interaction of plasma LDL with the cellular elements of the arterial wall is a stimulation of cholesterol esterification. These studies, coupled with the observation that cholesteryl esters, more than any other single component, increase in the atherosclerotic artery, suggest an important role of a stimulation in cholesterol esterification in the pathogenesis of atherosclerosis.", "contents": "Stimulation of cholesterol esterification in rhesus monkey arterial smooth muscle cells. The influence of homologous high density lipoprotein (HDL) and low density lipoprotein (LDL) and of whole hypercholesterolemic serum on the esterification of oleic acid and cholesterol was studied in rhesus monkey arterial smooth muscle cells. Whole hypercholesterolemic serum and isolated LDL stimulated cholesterol esterification as much as 10-fold using either cholesterol-1,2-3H or oleate-1-14C as substrate. At the same concentrations of cholesterol, HDL stimulated cholesterol esterification to a lesser extent, to a maximum of 3-fold. Associated with the stimulation of cholesterol esterification by LDL or whole hypercholesterolemic serum was a greater than 10-fold increase in the cholesteryl ester content of the arterial smooth muscle cells. Esterification to cholesterol reached a maximum after 8-12 hours of culture with either hypercholesterolemic serum or LDL. The stimulation of esterification was specific for esterification to cholesterol because there was little change in incorporation of fatty acid into triglycerides and phospholipids. These studies provide further evidence that a major consequence of the interaction of plasma LDL with the cellular elements of the arterial wall is a stimulation of cholesterol esterification. These studies, coupled with the observation that cholesteryl esters, more than any other single component, increase in the atherosclerotic artery, suggest an important role of a stimulation in cholesterol esterification in the pathogenesis of atherosclerosis."}
{"id": "PMID:191213", "title": "Effect of intrarenal angiotensin II blockade on renal function in conscious dogs.", "content": "The effects of intrarenal infusion of 1-sar-8-ala angiotension II (P 113) and a converting enzyme inhibitor, SQ 20881, at doses that did not affect systemic blood pressure (2.0 mug/kg per min) were studied in conscious, uninephrectomized dogs. In dogs receiving approximately equal to 5 mEq/day of sodium, intrarenal infusion of P 113 increased renal blood flow (RBF) from 219.8 +/- 32.3 to 282.7 +/- 20.0 ml/min (P less than 0.004), and with intrarenal SQ 20881 infusion from 215.3 +/- 14.2 to 278.0 +/- 22.2 ml/min (p less than 0.005). In sodium-restricted dogs (approximately equal to 5 mEq/day), glomerular filtration rate (GFR) also increased with intrarenal P 113 infusion from 57.9 +/- 5.7 to 66.3 +/- 6.6 ml/min (P less than 0.05), and with SQ 20881 infusion from 43.1 +/- 2.1 to 55.7 +/- 4.5 ml/min (P less than 0.01). Dogs on approximately equal to 5 mEq/day of sodium showed significant increases in plasma renin activity (PRA) with intrarenal infusion of the peptides, unmasking a negative feedback inhibition of renin release by angiotensin II. No increases in RBF, GFR, or PRA were seen with infusion without inhibitors, or in dogs give P 113 or SQ 20881 while on approximately equal to 80 mEq/day of sodium. In addition, angiotensin II inhibition increased sodium excretion during sodium restriction. These findings suggest that intrarenal angiotensin II is intimately involved in renal responses to sodium restriction which result in conservation of sodium and water.", "contents": "Effect of intrarenal angiotensin II blockade on renal function in conscious dogs. The effects of intrarenal infusion of 1-sar-8-ala angiotension II (P 113) and a converting enzyme inhibitor, SQ 20881, at doses that did not affect systemic blood pressure (2.0 mug/kg per min) were studied in conscious, uninephrectomized dogs. In dogs receiving approximately equal to 5 mEq/day of sodium, intrarenal infusion of P 113 increased renal blood flow (RBF) from 219.8 +/- 32.3 to 282.7 +/- 20.0 ml/min (P less than 0.004), and with intrarenal SQ 20881 infusion from 215.3 +/- 14.2 to 278.0 +/- 22.2 ml/min (p less than 0.005). In sodium-restricted dogs (approximately equal to 5 mEq/day), glomerular filtration rate (GFR) also increased with intrarenal P 113 infusion from 57.9 +/- 5.7 to 66.3 +/- 6.6 ml/min (P less than 0.05), and with SQ 20881 infusion from 43.1 +/- 2.1 to 55.7 +/- 4.5 ml/min (P less than 0.01). Dogs on approximately equal to 5 mEq/day of sodium showed significant increases in plasma renin activity (PRA) with intrarenal infusion of the peptides, unmasking a negative feedback inhibition of renin release by angiotensin II. No increases in RBF, GFR, or PRA were seen with infusion without inhibitors, or in dogs give P 113 or SQ 20881 while on approximately equal to 80 mEq/day of sodium. In addition, angiotensin II inhibition increased sodium excretion during sodium restriction. These findings suggest that intrarenal angiotensin II is intimately involved in renal responses to sodium restriction which result in conservation of sodium and water."}
{"id": "PMID:191214", "title": "Inhibition of sympathetic neurotransmission in canine blood vessels by adenosine and adenine nucleotides.", "content": "Adenosine and the adenine nucleotides caused a greater relaxation of strips of canine saphenous vein and tibial artery when they had been contracted by nerve stimulation than by exogenous norepinephrine. An infusion of adenosine into the dogs' lateral saphenous vein, perfused at constant flow, caused a greater relaxation of this vein when constricted by electrical stimulation of the lumbar sympathetic chain than by exogenous norepinephrine. That this difference was due to inhibition by these compounds of the output of neurotransmitter from the sympathetic nerve endings was demonstrated by column chromatographic analysis of the radioactivity in the superfusion fluid of vein strips, previously incubated with tritiated norepinephrine. Both adenosine and adenosine triphosphate (10(-5) M) reduced the efflux of 3H-norepinephrine during nerve stimulation with electrical impulses. Adenosine also reduced the efflux caused by potassium (30 mM), but not that caused by tyramine (6 X 10(-6) M). Theophylline antagonized the inhibitory effect of adenosine on the sympathetic neurotransmission. We found that at 4 X 10(-4) M adenosine triphosphate still caused a decreased efflux of neurotransmitter during electrical stimulation, but with adenosine the 3H-norepinephrine efflux no longer decreased and the overflow of deaminated compounds increased. Furthermore, the same concentration of adenosine increased the efflux of 3H-norepinephrine and deaminated compounds in unstimulated strips, and the increase of 3H-norepinephrine was enhanced after monoamine oxidase inhibition. Thus, we conclude that at higher concentrations adenosine increases the intraneuronal leakage of norepinephrine out of the storage vesicles.", "contents": "Inhibition of sympathetic neurotransmission in canine blood vessels by adenosine and adenine nucleotides. Adenosine and the adenine nucleotides caused a greater relaxation of strips of canine saphenous vein and tibial artery when they had been contracted by nerve stimulation than by exogenous norepinephrine. An infusion of adenosine into the dogs' lateral saphenous vein, perfused at constant flow, caused a greater relaxation of this vein when constricted by electrical stimulation of the lumbar sympathetic chain than by exogenous norepinephrine. That this difference was due to inhibition by these compounds of the output of neurotransmitter from the sympathetic nerve endings was demonstrated by column chromatographic analysis of the radioactivity in the superfusion fluid of vein strips, previously incubated with tritiated norepinephrine. Both adenosine and adenosine triphosphate (10(-5) M) reduced the efflux of 3H-norepinephrine during nerve stimulation with electrical impulses. Adenosine also reduced the efflux caused by potassium (30 mM), but not that caused by tyramine (6 X 10(-6) M). Theophylline antagonized the inhibitory effect of adenosine on the sympathetic neurotransmission. We found that at 4 X 10(-4) M adenosine triphosphate still caused a decreased efflux of neurotransmitter during electrical stimulation, but with adenosine the 3H-norepinephrine efflux no longer decreased and the overflow of deaminated compounds increased. Furthermore, the same concentration of adenosine increased the efflux of 3H-norepinephrine and deaminated compounds in unstimulated strips, and the increase of 3H-norepinephrine was enhanced after monoamine oxidase inhibition. Thus, we conclude that at higher concentrations adenosine increases the intraneuronal leakage of norepinephrine out of the storage vesicles."}
{"id": "PMID:191215", "title": "HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study.", "content": "The relation between coronary heart disease (CHD) prevalence and fasting lipid levels was assessed by a case-control study in five populations with a total of 6859 men and women of black, Japanese and white ancestry drawn from subjects aged 40 years and older from populations in Albany, Framingham, Evans County, Honolulu and San Francisco. In each major study group mean levels of high density lipoprotein (HDL) cholesterol were lower in persons with CHD than in those without the disease. The average difference was small -- typically 3-4 mg/dl -- but statistically significant. It was found in most age-race-sex specific groups. The inverse HDL cholesterol-CHD association was not appreciably diminished when adjusted for levels of low density lipoprotein (LDL) cholesterol and triglyceride. LDL, totoal cholesterol and triglycerides were directly related to CHD prevalence; surprisingly, these findings were less uniformly present in the various study groups than the inverse HDL cholesterol-CHD association.", "contents": "HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study. The relation between coronary heart disease (CHD) prevalence and fasting lipid levels was assessed by a case-control study in five populations with a total of 6859 men and women of black, Japanese and white ancestry drawn from subjects aged 40 years and older from populations in Albany, Framingham, Evans County, Honolulu and San Francisco. In each major study group mean levels of high density lipoprotein (HDL) cholesterol were lower in persons with CHD than in those without the disease. The average difference was small -- typically 3-4 mg/dl -- but statistically significant. It was found in most age-race-sex specific groups. The inverse HDL cholesterol-CHD association was not appreciably diminished when adjusted for levels of low density lipoprotein (LDL) cholesterol and triglyceride. LDL, totoal cholesterol and triglycerides were directly related to CHD prevalence; surprisingly, these findings were less uniformly present in the various study groups than the inverse HDL cholesterol-CHD association."}
{"id": "PMID:191216", "title": "The electrophoretic mobility of lipoprotein X in postheparin plasma.", "content": "After incubation whole plasma and low density lipoproteins (LDL) taken before and 10 min after intravenous administration of heparin, from a patient with primary biliary cirrhosis and a patient with familial lecithin:cholesterol acyltransferase (LCAT) deficiency, have been tested for the presence of lipoprotein X (LP-X) by agar gel electrophoresis. LP-X was present in preheparin whole plasma and LDL. No precipitation lines on the cathodal side of the wells, indicating the absence of LP-X, were seen after electrophoresis of postheparin plasma and LDL. Immunodiffusion revealed the presence of apo-beta-lipoproteins and LP-X in preheparin as well as postheparin LDL. After gel filtration three subfractions and similar patterns were observed in the preheparin and postheparin LDL. Electronmicroscopical examination of the intermediate subfractions showed LP-X-like particles in preheparin and postheparin samples. These observations indicate a changed electrophoretic mobility in agar gel of postheparin LP-X, giving a false negative LP-X test by the conventional agar gel electrophoresis.", "contents": "The electrophoretic mobility of lipoprotein X in postheparin plasma. After incubation whole plasma and low density lipoproteins (LDL) taken before and 10 min after intravenous administration of heparin, from a patient with primary biliary cirrhosis and a patient with familial lecithin:cholesterol acyltransferase (LCAT) deficiency, have been tested for the presence of lipoprotein X (LP-X) by agar gel electrophoresis. LP-X was present in preheparin whole plasma and LDL. No precipitation lines on the cathodal side of the wells, indicating the absence of LP-X, were seen after electrophoresis of postheparin plasma and LDL. Immunodiffusion revealed the presence of apo-beta-lipoproteins and LP-X in preheparin as well as postheparin LDL. After gel filtration three subfractions and similar patterns were observed in the preheparin and postheparin LDL. Electronmicroscopical examination of the intermediate subfractions showed LP-X-like particles in preheparin and postheparin samples. These observations indicate a changed electrophoretic mobility in agar gel of postheparin LP-X, giving a false negative LP-X test by the conventional agar gel electrophoresis."}
{"id": "PMID:191217", "title": "Prolyl hydroxylase activity in human normal skins and post-burn scars.", "content": "Post-burn granulation tissues showed an extraordinary high prolyl hydroxylase (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase) activity, 25 to 50 times higher than the mean value of human normal skins from the frontal thighs of 15 subjects, 385 +/- 247 (S.D.) cpm/min/g of wet weight tissue. The activity in the scars decreased sharply within 4 to 5 months, and then gradually decreased to the normal range after 2 years or so. Well-aged scars tended to show lower values than the mean value of normal skins.", "contents": "Prolyl hydroxylase activity in human normal skins and post-burn scars. Post-burn granulation tissues showed an extraordinary high prolyl hydroxylase (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase) activity, 25 to 50 times higher than the mean value of human normal skins from the frontal thighs of 15 subjects, 385 +/- 247 (S.D.) cpm/min/g of wet weight tissue. The activity in the scars decreased sharply within 4 to 5 months, and then gradually decreased to the normal range after 2 years or so. Well-aged scars tended to show lower values than the mean value of normal skins."}
{"id": "PMID:191218", "title": "Type III hyperlipoproteinemia: a comparative study of current diagnostic techniques.", "content": "Research into the prevalence, genetic transmission and pathophysiology of Type III hyperlipoproteinemia has suffered from the lack of a practical specific diagnostic procedure. In this study, very low density lipoprotein (VLDL) compositional criteria were established in a population lacking the beta-migrating VLDL characteristic of this disorder. Diagnosis by these criteria was compared to diagnosis using current criteria for the Type III lipoprotein pattern. In addition two techniques for detecting Type III without preliminary VLDL isolation by ultracentrifugation were evaluated. Plasma triglyceride (TG) concentration dependent cutlines for the compositional criteria reduced false positives at low TG levels and false negatives at high TG levels. Furthermore, an agarose electrophoresis heparin-manganese precipitation technique was effective for screening for a possible Type III pattern in plasma whereas the combination agarose-polyacrylamide gel electrophoresis system was not effective.", "contents": "Type III hyperlipoproteinemia: a comparative study of current diagnostic techniques. Research into the prevalence, genetic transmission and pathophysiology of Type III hyperlipoproteinemia has suffered from the lack of a practical specific diagnostic procedure. In this study, very low density lipoprotein (VLDL) compositional criteria were established in a population lacking the beta-migrating VLDL characteristic of this disorder. Diagnosis by these criteria was compared to diagnosis using current criteria for the Type III lipoprotein pattern. In addition two techniques for detecting Type III without preliminary VLDL isolation by ultracentrifugation were evaluated. Plasma triglyceride (TG) concentration dependent cutlines for the compositional criteria reduced false positives at low TG levels and false negatives at high TG levels. Furthermore, an agarose electrophoresis heparin-manganese precipitation technique was effective for screening for a possible Type III pattern in plasma whereas the combination agarose-polyacrylamide gel electrophoresis system was not effective."}
{"id": "PMID:191219", "title": "Excretion of galactitol in the urine of heterozygotes of both forms of galactosemia.", "content": "In 36 heterozygotes with Gal-1-PUT deficiency and 3 heterozygotes with galactokinase deficiency galactitol (and galactose) was determined in the urine 2 and 4 h after an intravenous injection of 350 mg galactose/kg body weight (maximum dosis in adults 16 g). For the sake of comparison 10 healthy children and 5 adults, also 4 homozygotes with Gal-1-PUT deficiency and one sick child with galactokinase deficiency were included in this study. The heterozygotes with Gal-1-PUT deficiency demonstrated the same galactitol excretion as the healthy probands, while heterozygotes with galactokinase deficiency excreted a four-fold higher quantity of galactitol than the healthy and heterozygous probands of Gal-1-PUT deficiency. The child with the galactokinase deficiency excreted galactitol for a period of more than 24 h. These results are discussed.", "contents": "Excretion of galactitol in the urine of heterozygotes of both forms of galactosemia. In 36 heterozygotes with Gal-1-PUT deficiency and 3 heterozygotes with galactokinase deficiency galactitol (and galactose) was determined in the urine 2 and 4 h after an intravenous injection of 350 mg galactose/kg body weight (maximum dosis in adults 16 g). For the sake of comparison 10 healthy children and 5 adults, also 4 homozygotes with Gal-1-PUT deficiency and one sick child with galactokinase deficiency were included in this study. The heterozygotes with Gal-1-PUT deficiency demonstrated the same galactitol excretion as the healthy probands, while heterozygotes with galactokinase deficiency excreted a four-fold higher quantity of galactitol than the healthy and heterozygous probands of Gal-1-PUT deficiency. The child with the galactokinase deficiency excreted galactitol for a period of more than 24 h. These results are discussed."}
{"id": "PMID:191221", "title": "Lung tumours and ACTH production.", "content": "ACTH levels measured by N- and C-terminal immunoassays and cytochemical bioassay, were measured in fourteen lung tumours not associated with the ectopic ACTH syndrome and in macroscopically normal lung tissue taken from the same patients at thoracotomy. Significant concentrations of immunocative (greater than 3 ng/g wet weight) and bioactive (greater than 0.2 ng/g wet weight) ACTH were found in all the carcinoid and oat cell tumours (n=9), a combined tumour (poorly differentiated adenocarcinoma with large cell carcinoid elements), and a poorly differentiated squamous cell tumour. All the carcinoid tumours contained more C- than N-terminal ACTH immunoactivity. The squamous cell tumours (n=2), anaplastic tumours (n=2) and adenocarcinoma contained insignificant ACTH levels. There was a good correlation between the ACTH levels and the presence of secretory granules in the tumours examined ultrastructually. All the macroscopically normal samples of lung tissue contained immuno and bioactive ACTH-like material, the levels of which correlated well with ACTH levels in the tumour tissue. It is suggested that all lung tumours of carcinoid or oat cell type synthesize ACTH-like materials although clinical evidence of the ectopic ACTH syndrome may be absent. The presence of ACTH-like materials in non-tumorous lung tissue in patients with lung cancer may indicate a low level of ACTH production throughout the lung or sequestration of ACTH containing granules secreted by the tumour.", "contents": "Lung tumours and ACTH production. ACTH levels measured by N- and C-terminal immunoassays and cytochemical bioassay, were measured in fourteen lung tumours not associated with the ectopic ACTH syndrome and in macroscopically normal lung tissue taken from the same patients at thoracotomy. Significant concentrations of immunocative (greater than 3 ng/g wet weight) and bioactive (greater than 0.2 ng/g wet weight) ACTH were found in all the carcinoid and oat cell tumours (n=9), a combined tumour (poorly differentiated adenocarcinoma with large cell carcinoid elements), and a poorly differentiated squamous cell tumour. All the carcinoid tumours contained more C- than N-terminal ACTH immunoactivity. The squamous cell tumours (n=2), anaplastic tumours (n=2) and adenocarcinoma contained insignificant ACTH levels. There was a good correlation between the ACTH levels and the presence of secretory granules in the tumours examined ultrastructually. All the macroscopically normal samples of lung tissue contained immuno and bioactive ACTH-like material, the levels of which correlated well with ACTH levels in the tumour tissue. It is suggested that all lung tumours of carcinoid or oat cell type synthesize ACTH-like materials although clinical evidence of the ectopic ACTH syndrome may be absent. The presence of ACTH-like materials in non-tumorous lung tissue in patients with lung cancer may indicate a low level of ACTH production throughout the lung or sequestration of ACTH containing granules secreted by the tumour."}
{"id": "PMID:191228", "title": "Continuity of care between the psychiatric hospital and public schools.", "content": "Seventy-five professionals from three psychiatric training hospitals were interviewed to ascertain their attitudes and stated practices concerning educational aftercare planning and implementation. Findings revealed that 75% of the professionals did not routinely contact the schools despite their acknowledgment of the school's potential for facilitating rehabilitation. Neither discipline nor hospital were related to attitudes or to reported behavior concerning the hospital's relationship with the school. Suggestions for improving the continuum of care are discussed.", "contents": "Continuity of care between the psychiatric hospital and public schools. Seventy-five professionals from three psychiatric training hospitals were interviewed to ascertain their attitudes and stated practices concerning educational aftercare planning and implementation. Findings revealed that 75% of the professionals did not routinely contact the schools despite their acknowledgment of the school's potential for facilitating rehabilitation. Neither discipline nor hospital were related to attitudes or to reported behavior concerning the hospital's relationship with the school. Suggestions for improving the continuum of care are discussed."}
{"id": "PMID:191230", "title": "Daily fluctuations in the plasma cortisol level of children with rheumatoid arthritis before and after treatment with tetracosactrin ('Cortrosyn Depot') and corticosteroid hormones.", "content": "Daily fluctuations in plasma cortisol levels were studied in three groups of children with rheumatoid arthritis. One group was untreated with hormones, the second treated with a depot preparation of tetracosactrin, and the third group with corticosteroid hormones. The results obtained were compared with the rhythm in normal children. The daily plasma cortisol fluctuations in children with rheumatoid arthritis who did not receive hormonal treatment differed from those of normal children by the presence of two distinct and characteristic cortisol levels: a peak between 8 a.m. and 12 noon and a minimal level between 4 p.m. and midnight (with a gradual rise after 4 p.m.). The curve of the daily cortisol rhythm in children with rheumatoid arthritis after tetracosactrin treatment was characteristic of the curve in normal children. Steroidtreated children with rheumatoid arthritis had virtually unchanged plasma cortisol concentrations throughout the day.", "contents": "Daily fluctuations in the plasma cortisol level of children with rheumatoid arthritis before and after treatment with tetracosactrin ('Cortrosyn Depot') and corticosteroid hormones. Daily fluctuations in plasma cortisol levels were studied in three groups of children with rheumatoid arthritis. One group was untreated with hormones, the second treated with a depot preparation of tetracosactrin, and the third group with corticosteroid hormones. The results obtained were compared with the rhythm in normal children. The daily plasma cortisol fluctuations in children with rheumatoid arthritis who did not receive hormonal treatment differed from those of normal children by the presence of two distinct and characteristic cortisol levels: a peak between 8 a.m. and 12 noon and a minimal level between 4 p.m. and midnight (with a gradual rise after 4 p.m.). The curve of the daily cortisol rhythm in children with rheumatoid arthritis after tetracosactrin treatment was characteristic of the curve in normal children. Steroidtreated children with rheumatoid arthritis had virtually unchanged plasma cortisol concentrations throughout the day."}
{"id": "PMID:191233", "title": "Perforation of the colon in unsuspected amebic colitis: report of two cases.", "content": "Two cases of amebic colitis that resulted in perforation of the colon, an ominous complication, are presented. The first was diagnosed preoperatively as acute ulcerative colitis with toxic megacolon, and the second as peritonitis complicating acute cholecystitis. In both instances the correct diagnosis was made after operation. The first patient recovered after colectomy and antiamebic therapy, but the second patient died in the early postoperative period, in septic shock. Amebic colitis occurs infrequently in the United States, and the diagnosis is rarely considered. In most cases an initial diagnosis of ulcerative or granulomatous colitis is made and the true diagnosis is recognized only after operation for colonic perforation or hepatic abscess. It is suggested that amebic colitis should be considered more frequently in cases of patients who have diarrhea. Stool examination for ova and parasites is often negative in amebic colitis. The IHA is usually positive in emebiasis, and should be performed early in casesof patients who have bloody diarrhea or other clinical symptons when amebiasis is suspected. Rectal biopsy is also a useful diagnostic approach, but failed to reveal amebae in one of our cases. Finally, it is suggested that operation be performed urgently when fulminating amebic colitis is not reversed by antiamebic therapy, when peritonitis occurs even with antiamebic treatment in progess, and for colonic perforation or toxic megacolon even when antiamebic therapy has not been indicated.", "contents": "Perforation of the colon in unsuspected amebic colitis: report of two cases. Two cases of amebic colitis that resulted in perforation of the colon, an ominous complication, are presented. The first was diagnosed preoperatively as acute ulcerative colitis with toxic megacolon, and the second as peritonitis complicating acute cholecystitis. In both instances the correct diagnosis was made after operation. The first patient recovered after colectomy and antiamebic therapy, but the second patient died in the early postoperative period, in septic shock. Amebic colitis occurs infrequently in the United States, and the diagnosis is rarely considered. In most cases an initial diagnosis of ulcerative or granulomatous colitis is made and the true diagnosis is recognized only after operation for colonic perforation or hepatic abscess. It is suggested that amebic colitis should be considered more frequently in cases of patients who have diarrhea. Stool examination for ova and parasites is often negative in amebic colitis. The IHA is usually positive in emebiasis, and should be performed early in casesof patients who have bloody diarrhea or other clinical symptons when amebiasis is suspected. Rectal biopsy is also a useful diagnostic approach, but failed to reveal amebae in one of our cases. Finally, it is suggested that operation be performed urgently when fulminating amebic colitis is not reversed by antiamebic therapy, when peritonitis occurs even with antiamebic treatment in progess, and for colonic perforation or toxic megacolon even when antiamebic therapy has not been indicated."}
{"id": "PMID:191234", "title": "[Simultaneous occurrence of primary hyperparathyroidism and pituitary Cushing's syndrome (author's transl)].", "content": "A case of primary hyperparathyroidism and coincidental Cushing's syndrome of hypothalamic-hypophyseal origin is reported. The hyperparathyroidism was based on an adenoma of the parathyroid glands and produced a severe hypercalcaemia (4.5 mmol/l) and calcinosis of kidneys and lungs. The Cushing's syndrome was caused by a hyperplasiogenic ACTH cell-adenoma of the pituitary which had induced a regulative hyperplasia of the ACTH-dependent zones of the adrenal cortex. The ultrastructure of the zona fasciculata and reticularis showed a conspicuous activation of the steroid hormone-producing organelles. The two endocrine diseases added together in skeleton, heart, duodenum, and pancreas. As a sign of hyperparathyroidism the osteoclastic absorption of the bone was strongly increased, whereas the bone formation was reduced due to the hypercortisolism. The pancreas showed a severe acute recurrence of chronic pancreatitis which was induced by a parathyrotoxic crisis. This was the immediate cause of death.", "contents": "[Simultaneous occurrence of primary hyperparathyroidism and pituitary Cushing's syndrome (author's transl)]. A case of primary hyperparathyroidism and coincidental Cushing's syndrome of hypothalamic-hypophyseal origin is reported. The hyperparathyroidism was based on an adenoma of the parathyroid glands and produced a severe hypercalcaemia (4.5 mmol/l) and calcinosis of kidneys and lungs. The Cushing's syndrome was caused by a hyperplasiogenic ACTH cell-adenoma of the pituitary which had induced a regulative hyperplasia of the ACTH-dependent zones of the adrenal cortex. The ultrastructure of the zona fasciculata and reticularis showed a conspicuous activation of the steroid hormone-producing organelles. The two endocrine diseases added together in skeleton, heart, duodenum, and pancreas. As a sign of hyperparathyroidism the osteoclastic absorption of the bone was strongly increased, whereas the bone formation was reduced due to the hypercortisolism. The pancreas showed a severe acute recurrence of chronic pancreatitis which was induced by a parathyrotoxic crisis. This was the immediate cause of death."}
{"id": "PMID:191237", "title": "Parathyroid hormone- and prostaglandin E1-response in a selected population of bone cells after repeated subculture and storage at -80C.", "content": "Five different cell populations, designated I to V, were isolated from minced newborn rat calveria by 5-sequential 20 min incubations with an enzyme mixture containing collagenase, elastase and DNAse. In primary culture, all five populations responded to parathyroid hormone (PTH) to a different degree, population IV giving the highest increase in cyclic-3'5'-adenosine monophosphate (cAMP) level. None of the five populations gave any response to calcitonin. Upon subsequent subcultures, all populations, except population IV, either lost or considerably decreased their response to PTH. Population IV gave a two to three-fold increase in cAMP concentration in response to PTH up to the third subculture. No morphological differences could be observed among the five populations. The third subculture of population IV cells that had been stored in 10% glycerol at -80C for four months was subsequently thawed and subcultured to the sixth subculture. These cells still responded to PTH with an increase in cAMP level. In a second experiment, 5 different cell populations designated I to V were isolated in a similar way by incubation with collagenase and DNAse. The maximum response to PTH was found in population 3. The preservation of the PTH-responsiveness of this population, after subculturing, freezing, storing in 10% glycerol at -80 C and subsequent subculturing, was likewise demonstrated. The hormone-responsiveness of cells from the sixth subculture of previously frozen and thawed population IV cells was further analyzed. These cells responded to PTH at a concentration of 0.1 U/ml to 5U/ml and to prostaglandin E1 (PGE1) at a concentration of 0.1 microng/ml to 10 microng/ml. The time course of action on population IV of PTH was found to be different from that of PGE1, suggesting a possible difference in the regulation of intracellular cAMP levels by these hormones.", "contents": "Parathyroid hormone- and prostaglandin E1-response in a selected population of bone cells after repeated subculture and storage at -80C. Five different cell populations, designated I to V, were isolated from minced newborn rat calveria by 5-sequential 20 min incubations with an enzyme mixture containing collagenase, elastase and DNAse. In primary culture, all five populations responded to parathyroid hormone (PTH) to a different degree, population IV giving the highest increase in cyclic-3'5'-adenosine monophosphate (cAMP) level. None of the five populations gave any response to calcitonin. Upon subsequent subcultures, all populations, except population IV, either lost or considerably decreased their response to PTH. Population IV gave a two to three-fold increase in cAMP concentration in response to PTH up to the third subculture. No morphological differences could be observed among the five populations. The third subculture of population IV cells that had been stored in 10% glycerol at -80C for four months was subsequently thawed and subcultured to the sixth subculture. These cells still responded to PTH with an increase in cAMP level. In a second experiment, 5 different cell populations designated I to V were isolated in a similar way by incubation with collagenase and DNAse. The maximum response to PTH was found in population 3. The preservation of the PTH-responsiveness of this population, after subculturing, freezing, storing in 10% glycerol at -80 C and subsequent subculturing, was likewise demonstrated. The hormone-responsiveness of cells from the sixth subculture of previously frozen and thawed population IV cells was further analyzed. These cells responded to PTH at a concentration of 0.1 U/ml to 5U/ml and to prostaglandin E1 (PGE1) at a concentration of 0.1 microng/ml to 10 microng/ml. The time course of action on population IV of PTH was found to be different from that of PGE1, suggesting a possible difference in the regulation of intracellular cAMP levels by these hormones."}
{"id": "PMID:191238", "title": "Opposite effects of ACTH and glucocorticoids on adrenal DNA synthesis in vivo.", "content": "Administration of ACTH to rapidly growing weanling rats results in an increase of DNA synthesis in adrenal and a decrease in liver. Dexamethasone administration decreases both adrenal and liver DNA synthesis. When both hormones were administered to the same animals, the liver DNA synthesis was similar to that observed with dexamethasone alone, but the DNA synthesis in adrenal was lower than that obtained with ACTH alone, yet higher than that observed with dexamethasone. The plasma levels of corticosterone were similar in animals treated with ACTH or with ACTH plus dexamethasone. Aminoglutethimide stimulated adrenal DNA synthesis, but less than ACTH. This substance overcame partially the inhibitory effects of dexamethasone on liver DNA synthesis but did not in adrenal. When both ACTH and aminoglutethimide were given simultaneously, adrenal DNA synthesis was higher than that observed with each substance alone. In all experiments in which adrenal cytosol DNA polymerase was studied, the activity varied in the same direction as DNA synthesis. These results indicate opposing effects of ACTH and glucocorticoids on adrenal DNA synthesis. The finding of a glucocorticoid effect on the adrenal is supported by the demonstration of a glucocorticoid specific binding protein in adrenal cytosol. Cycloheximide blocks the stimulatory action of ACTH on both steroidogenesis and DNA synthesis. Actinomycin D, as well as dexamethasone, blocks only the DNA synthesis-promoting action of ACTH. This latter result suggests some differences in the metabolic pathways by which ACTH controls steroidogenesis and growth in the adrenal cell.", "contents": "Opposite effects of ACTH and glucocorticoids on adrenal DNA synthesis in vivo. Administration of ACTH to rapidly growing weanling rats results in an increase of DNA synthesis in adrenal and a decrease in liver. Dexamethasone administration decreases both adrenal and liver DNA synthesis. When both hormones were administered to the same animals, the liver DNA synthesis was similar to that observed with dexamethasone alone, but the DNA synthesis in adrenal was lower than that obtained with ACTH alone, yet higher than that observed with dexamethasone. The plasma levels of corticosterone were similar in animals treated with ACTH or with ACTH plus dexamethasone. Aminoglutethimide stimulated adrenal DNA synthesis, but less than ACTH. This substance overcame partially the inhibitory effects of dexamethasone on liver DNA synthesis but did not in adrenal. When both ACTH and aminoglutethimide were given simultaneously, adrenal DNA synthesis was higher than that observed with each substance alone. In all experiments in which adrenal cytosol DNA polymerase was studied, the activity varied in the same direction as DNA synthesis. These results indicate opposing effects of ACTH and glucocorticoids on adrenal DNA synthesis. The finding of a glucocorticoid effect on the adrenal is supported by the demonstration of a glucocorticoid specific binding protein in adrenal cytosol. Cycloheximide blocks the stimulatory action of ACTH on both steroidogenesis and DNA synthesis. Actinomycin D, as well as dexamethasone, blocks only the DNA synthesis-promoting action of ACTH. This latter result suggests some differences in the metabolic pathways by which ACTH controls steroidogenesis and growth in the adrenal cell."}
{"id": "PMID:191239", "title": "Adrenal steroidogenic actions of cyclic nucleotide derivatives in the rat.", "content": "Fifteen 3',5'-cyclic nucleotides and related compounds were studied for ability to mimic the steroidogenic action of ACTH in rats in which secretion of ACTH and corticosterone were suppressed by treatment with betamethasone, or by hypophysectomy. Subcutaneous administration of 8-chloro-cAMP, at doses of 40 mg/kg or greater, elicited the secretion of corticosterone to normal plasma levels in both betamethasone-treated and hypophysectomized animals. Cyclic AMP, dbcAMP, 8-methylthio-cAMP, 8-hydroxy-cAMP and the 6-chloro-8-aminopurine cyclic ribotide analog of cAMP also displayed steroidogenic activity in the betamethasone-treated rat; cGMP, 8-bromo-cGMP and 8-benzylthio-cGMP were inactive. Each of the steroidogenic derivatives of cAMP also displayed ability to activate steroidogenesis in isolated rat adrenal cells. These experiments demonstrate that various derivatives of cAMP mimic the adrenal steroidogenic action of ACTH, in vivo. Structure-activity comparisons support a steroidogenic mechanism involving direct activation by the nucleotides of cAMP-dependent protein kinase of the adrenal cortex.", "contents": "Adrenal steroidogenic actions of cyclic nucleotide derivatives in the rat. Fifteen 3',5'-cyclic nucleotides and related compounds were studied for ability to mimic the steroidogenic action of ACTH in rats in which secretion of ACTH and corticosterone were suppressed by treatment with betamethasone, or by hypophysectomy. Subcutaneous administration of 8-chloro-cAMP, at doses of 40 mg/kg or greater, elicited the secretion of corticosterone to normal plasma levels in both betamethasone-treated and hypophysectomized animals. Cyclic AMP, dbcAMP, 8-methylthio-cAMP, 8-hydroxy-cAMP and the 6-chloro-8-aminopurine cyclic ribotide analog of cAMP also displayed steroidogenic activity in the betamethasone-treated rat; cGMP, 8-bromo-cGMP and 8-benzylthio-cGMP were inactive. Each of the steroidogenic derivatives of cAMP also displayed ability to activate steroidogenesis in isolated rat adrenal cells. These experiments demonstrate that various derivatives of cAMP mimic the adrenal steroidogenic action of ACTH, in vivo. Structure-activity comparisons support a steroidogenic mechanism involving direct activation by the nucleotides of cAMP-dependent protein kinase of the adrenal cortex."}
{"id": "PMID:191240", "title": "Interaction of cyclic AMP and alloxan on insulin secretion in isolated rat islets perifused in vitro.", "content": "The interaction of alloxan and cyclic AMP on glucose-induced insulin secretion was studied with the use of isolated rat islet perifusion. Simultaneous perifusion with cyclic AMP and alloxan did not protect the islets against the effect of alloxan. However, addition of dibutyryl cyclic AMP to the alloxan solution produced 40% protection of glucose-induced insulin secretion. Partial protection was obtained with either theophylline (41%) or caffeine alone (54%), and the addition of 1 mg/ml glucose to the theophylline or caffeine solution provided greater than 68% protection. The levels of islet tissue cyclic AMP were more than 2.1 times that of islets not protected against the alloxan effect, when partial or nearly complete reversal of the inhibitory action of alloxan on glucose-induced insulin secretion was effected by theophylline or caffeine. These results suggest that cyclic AMP affords partial protection against the effect of alloxan on glucose-induced insulin secretion.", "contents": "Interaction of cyclic AMP and alloxan on insulin secretion in isolated rat islets perifused in vitro. The interaction of alloxan and cyclic AMP on glucose-induced insulin secretion was studied with the use of isolated rat islet perifusion. Simultaneous perifusion with cyclic AMP and alloxan did not protect the islets against the effect of alloxan. However, addition of dibutyryl cyclic AMP to the alloxan solution produced 40% protection of glucose-induced insulin secretion. Partial protection was obtained with either theophylline (41%) or caffeine alone (54%), and the addition of 1 mg/ml glucose to the theophylline or caffeine solution provided greater than 68% protection. The levels of islet tissue cyclic AMP were more than 2.1 times that of islets not protected against the alloxan effect, when partial or nearly complete reversal of the inhibitory action of alloxan on glucose-induced insulin secretion was effected by theophylline or caffeine. These results suggest that cyclic AMP affords partial protection against the effect of alloxan on glucose-induced insulin secretion."}
{"id": "PMID:191241", "title": "Evolution of prolactin receptors in rabbit mammary gland during pregnancy and lactation.", "content": "The numbers and affinity of prolactin receptors in the rabbit mammary gland were determined during pregnancy and early lactation under conditions in which the endogenous lactogenic hormone was depleted by means of the compound CB 154. In untreated rabbits the number of prolactin binding sites per mg protein increased from 25 +/- 3 (SE) fmol at Day 14 of gestation to 54.8 +/- 5.8 fmol/mg at Day 22, after which binding declined to 14.2 +/- 8.5 fmol/mg, then increased in late pregnancy and during lactation to 110.5 +/- 11.5 fmol/mg at Day 28. In animals treated with CB 154, binding was always higher than in non-treated animals, with a peak during pregnancy of 149 +/- 24 fmol/mg at Day 22. After declining in late pregnancy, the number of receptors was highest at Day 6 of lactation (257.4 +/- 34.6 fmol/mg). There is an almost linear increase in the weight of the mammary gland from Day 14 of pregnancy until Day 6 of lactation and this increase is unaffected (except at Day 6 of lactation) by CB 154 treatment. It was observed that prolactin receptors remain at a relatively low and constant level while mammary development (mammogenesis) takes place. The onset of milk secretion parallels a striking increase (greater than 500%) in the number of prolactin receptors (expressed per total mammary gland or per cell) after parturition has occurred. These results are discussed with emphasis on the mechanisms through which hormonal balances during pregnancy and lactation may modulate the amount of receptors per cell, hence its sensitivity to lactogenic hormones.", "contents": "Evolution of prolactin receptors in rabbit mammary gland during pregnancy and lactation. The numbers and affinity of prolactin receptors in the rabbit mammary gland were determined during pregnancy and early lactation under conditions in which the endogenous lactogenic hormone was depleted by means of the compound CB 154. In untreated rabbits the number of prolactin binding sites per mg protein increased from 25 +/- 3 (SE) fmol at Day 14 of gestation to 54.8 +/- 5.8 fmol/mg at Day 22, after which binding declined to 14.2 +/- 8.5 fmol/mg, then increased in late pregnancy and during lactation to 110.5 +/- 11.5 fmol/mg at Day 28. In animals treated with CB 154, binding was always higher than in non-treated animals, with a peak during pregnancy of 149 +/- 24 fmol/mg at Day 22. After declining in late pregnancy, the number of receptors was highest at Day 6 of lactation (257.4 +/- 34.6 fmol/mg). There is an almost linear increase in the weight of the mammary gland from Day 14 of pregnancy until Day 6 of lactation and this increase is unaffected (except at Day 6 of lactation) by CB 154 treatment. It was observed that prolactin receptors remain at a relatively low and constant level while mammary development (mammogenesis) takes place. The onset of milk secretion parallels a striking increase (greater than 500%) in the number of prolactin receptors (expressed per total mammary gland or per cell) after parturition has occurred. These results are discussed with emphasis on the mechanisms through which hormonal balances during pregnancy and lactation may modulate the amount of receptors per cell, hence its sensitivity to lactogenic hormones."}
{"id": "PMID:191242", "title": "Evidence for preferential effects of parathyroid hormone, calcitonin and adenosine on bone and periosteum.", "content": "In order to explore the distribution of hormone-responsive cells in skeletal tissues, we have examined the effects of synthetic bovine parathyroid hormone N-terminal peptide (bPTH 1-34) and salmon calcitonin (sCT) on cyclic AMP levels in periosteum-free rat calvaria, segments of periosteum, and in isolated cells dispersed from each tissue by collagenase digestion. Synthetic bovine PTH increased cyclic AMP levels to a greater degree in calvaria and in isolated bone cells than in the periosteal segments and cells, whereas sCT was more effective in the periosteal than in the bone systems. Primary cultures prepared from bone and periosteal cell populations exhibited progressive increases in their responsiveness to bPTH (1-34) and progressive decreases in responsiveness to sCT. After six days in the culture, bone cells failed to respond to sCT, and sCT did not modify their response simultaneously added bPTH (1-34). Six-day periosteal cell cultures exhibited residual sCT responsivity and an additive response upon simultaneous exposure to high concentrations of bPTH (1-34) and sCT suggesting separate sites of hormone action. Adenosine, a known stimulator of bone cell adenylyl cyclase, caused a greater increase in periosteal cell than in bone cell cyclic AMP. bPTH (1-34)-responsive cells which enrich periosteum-free bone may be osteoblasts, in view of their histological prominence in this tissue and in the bone cell isolates. Periosteal cells which responded to sCT and to adenosine preferentially are unidentified. Although periosteal segments contained numerous fibroblast-like cells, skin fibroblasts cultured from the same fetuses were sCT-insensitive. Growth in primary culture appears to alter the number of hormone-responsive cells or responsiveness of existing cells to each hormone, or both.", "contents": "Evidence for preferential effects of parathyroid hormone, calcitonin and adenosine on bone and periosteum. In order to explore the distribution of hormone-responsive cells in skeletal tissues, we have examined the effects of synthetic bovine parathyroid hormone N-terminal peptide (bPTH 1-34) and salmon calcitonin (sCT) on cyclic AMP levels in periosteum-free rat calvaria, segments of periosteum, and in isolated cells dispersed from each tissue by collagenase digestion. Synthetic bovine PTH increased cyclic AMP levels to a greater degree in calvaria and in isolated bone cells than in the periosteal segments and cells, whereas sCT was more effective in the periosteal than in the bone systems. Primary cultures prepared from bone and periosteal cell populations exhibited progressive increases in their responsiveness to bPTH (1-34) and progressive decreases in responsiveness to sCT. After six days in the culture, bone cells failed to respond to sCT, and sCT did not modify their response simultaneously added bPTH (1-34). Six-day periosteal cell cultures exhibited residual sCT responsivity and an additive response upon simultaneous exposure to high concentrations of bPTH (1-34) and sCT suggesting separate sites of hormone action. Adenosine, a known stimulator of bone cell adenylyl cyclase, caused a greater increase in periosteal cell than in bone cell cyclic AMP. bPTH (1-34)-responsive cells which enrich periosteum-free bone may be osteoblasts, in view of their histological prominence in this tissue and in the bone cell isolates. Periosteal cells which responded to sCT and to adenosine preferentially are unidentified. Although periosteal segments contained numerous fibroblast-like cells, skin fibroblasts cultured from the same fetuses were sCT-insensitive. Growth in primary culture appears to alter the number of hormone-responsive cells or responsiveness of existing cells to each hormone, or both."}
{"id": "PMID:191243", "title": "Enhancement of [3H-methyl]thymidine incorporation and replication of rat chondrocytes grown in tissue culture by plasma, tissue extracts and vasopressin.", "content": "A pituitary mitogenic peptide, which stimulates cellular replication of a variety of cells maintained in tissue culture, has been identified by other investigators. To study this mitogenic substance, we developed an assay to measure mitogenic substances utilizing fetal rat chondrocytes grown in monolayer culture. Mitogenic activity of added test substances was determined by [3H-methyl]thymidine incorporation into trichloroacetic acid insoluble cell products and increase in total cell number after 24 h exposure. Extracts of whole pituitary glands were more potent in stimulating these cellular indices than either those of liver or muscle, confirming that the chondrocytes are sensitive to the described mitogen. Identically prepared extracts of either anterior or posterior pituitary lobes were mitogenic indicating the presence of two or more mitogenic substances in crude pituitary extracts. Synthetic lysine vasopressin and a beef pitressin concentrate stimulated thymidine incorporation into chondrocytes in the absence of calf serum and this effect was additive to that of calf serum, suggesting that the mitogenic substance of posterior pituitary extracts was vasopressin. The maximum effective dose of vasopressin leading to an increase in either thymidine incorporation or total cell number was between 100 to 500 pg/ml, and as little as 50 pg/ml of hormone elicited an increase in total cell number. The mitogenic effect of both vasopressin and calf serum on chondrocytes was partially inhibited by 1 X 10(-4)M N, O'dibutryl cyclic adenosine 3',5' monophosphate suggesting that cell division of chrondrocytes may be under tonic control by the andenylyl cyclase system. We conclude that vasopressin is a potent mitogen for chondrocytes maintained in tissue culture and its presence must be rigorously excluded in evaluating mitogenic activity of pituitary or serum concentrates.", "contents": "Enhancement of [3H-methyl]thymidine incorporation and replication of rat chondrocytes grown in tissue culture by plasma, tissue extracts and vasopressin. A pituitary mitogenic peptide, which stimulates cellular replication of a variety of cells maintained in tissue culture, has been identified by other investigators. To study this mitogenic substance, we developed an assay to measure mitogenic substances utilizing fetal rat chondrocytes grown in monolayer culture. Mitogenic activity of added test substances was determined by [3H-methyl]thymidine incorporation into trichloroacetic acid insoluble cell products and increase in total cell number after 24 h exposure. Extracts of whole pituitary glands were more potent in stimulating these cellular indices than either those of liver or muscle, confirming that the chondrocytes are sensitive to the described mitogen. Identically prepared extracts of either anterior or posterior pituitary lobes were mitogenic indicating the presence of two or more mitogenic substances in crude pituitary extracts. Synthetic lysine vasopressin and a beef pitressin concentrate stimulated thymidine incorporation into chondrocytes in the absence of calf serum and this effect was additive to that of calf serum, suggesting that the mitogenic substance of posterior pituitary extracts was vasopressin. The maximum effective dose of vasopressin leading to an increase in either thymidine incorporation or total cell number was between 100 to 500 pg/ml, and as little as 50 pg/ml of hormone elicited an increase in total cell number. The mitogenic effect of both vasopressin and calf serum on chondrocytes was partially inhibited by 1 X 10(-4)M N, O'dibutryl cyclic adenosine 3',5' monophosphate suggesting that cell division of chrondrocytes may be under tonic control by the andenylyl cyclase system. We conclude that vasopressin is a potent mitogen for chondrocytes maintained in tissue culture and its presence must be rigorously excluded in evaluating mitogenic activity of pituitary or serum concentrates."}
{"id": "PMID:191244", "title": "Growth rate and secretion of pituitary hormones in relation to age and chronic treatment with thyrotropin-releasing hormone in prepubertal dairy heifers.", "content": "Holstein heifers were treated with synthetic thyrotropin-releasing hormone (TRH) or saline twice daily from one week through 6 mo of age. Plasma concentrations of prolactin (PRL) and thyrotropin (TSH) were elevated (P less than .01) within 30 min after the first TRH injection (1 week of age). At 1 and 3 mo of treatment, PRL and TSH increased in response to TRH, although the TSH response was reduced (P less than .01) as compared to the first day of treatment. Although plasma growth hormone (GH) appeared to be elevated following the first TRH injection, this effect was not statistically significant (P less than .05), nor was it significantly influenced by treatment following subsequent TRH injections. None of the 3 hormones, PRL, TSH or GH, was elevated following the final TRH injection at 6 mo of age. In contrast, plasma concentrations of PRL and TSH were increased in a control heifer injected with TRH at 6 mo. These data indicate that hormonal responsiveness to TRH stimulation decreases with continued twice daily treatment at doses of TRH used in the present studies. Examination of weight gains indicated that chronic treatment with TRH was associated with increased growth rate through 6 mo of age (10.6% increased average daily gains P less than .10), which was exhibited in a steeper slope (P less than .05) of the growth curve in the TRH group. Feed intake was slightly greater in TRH heifers, although feed efficiency (kg feed/kg gain) was not different between the two groups. Plasma concentrations of PRL increased (P less than .01) with age (r = +0.938) in control heifers while plasma TSH and GH were not significantly related to age. This observation establishes a positive correlative relationship between PRL secretion and the approach of puberty in the dairly heirfer. It was also noted that elevation of PRL secretion by TRH treatment was associated with significant advancement of age at first observed estrus (9.4 vs. - 10.5 mo) suggesting that a functional relationship between PRL secretion and puberty may exist in dairy heifers.", "contents": "Growth rate and secretion of pituitary hormones in relation to age and chronic treatment with thyrotropin-releasing hormone in prepubertal dairy heifers. Holstein heifers were treated with synthetic thyrotropin-releasing hormone (TRH) or saline twice daily from one week through 6 mo of age. Plasma concentrations of prolactin (PRL) and thyrotropin (TSH) were elevated (P less than .01) within 30 min after the first TRH injection (1 week of age). At 1 and 3 mo of treatment, PRL and TSH increased in response to TRH, although the TSH response was reduced (P less than .01) as compared to the first day of treatment. Although plasma growth hormone (GH) appeared to be elevated following the first TRH injection, this effect was not statistically significant (P less than .05), nor was it significantly influenced by treatment following subsequent TRH injections. None of the 3 hormones, PRL, TSH or GH, was elevated following the final TRH injection at 6 mo of age. In contrast, plasma concentrations of PRL and TSH were increased in a control heifer injected with TRH at 6 mo. These data indicate that hormonal responsiveness to TRH stimulation decreases with continued twice daily treatment at doses of TRH used in the present studies. Examination of weight gains indicated that chronic treatment with TRH was associated with increased growth rate through 6 mo of age (10.6% increased average daily gains P less than .10), which was exhibited in a steeper slope (P less than .05) of the growth curve in the TRH group. Feed intake was slightly greater in TRH heifers, although feed efficiency (kg feed/kg gain) was not different between the two groups. Plasma concentrations of PRL increased (P less than .01) with age (r = +0.938) in control heifers while plasma TSH and GH were not significantly related to age. This observation establishes a positive correlative relationship between PRL secretion and the approach of puberty in the dairly heirfer. It was also noted that elevation of PRL secretion by TRH treatment was associated with significant advancement of age at first observed estrus (9.4 vs. - 10.5 mo) suggesting that a functional relationship between PRL secretion and puberty may exist in dairy heifers."}
{"id": "PMID:191245", "title": "Identification of \"angiotensin immunoreactive material\" in rat kidney.", "content": "The reported presence of large quantities of a high molecular weight form of angiotensin I and II in renin granules from rat kidney cortex was investigated. Subcellular fractionation by differential centrifugation and isopycnic gradient centrifugation confirmed the presence of 'angiotensin I immunoreactive material,' but the distribution resembled that of lysosomes rather than renin granules, mitochondria or protein. The material did not possess pressor properties, was stable to incubation at 37 C and was precipitated by ethanol. Incubation of subcellular fractions with peptidase inhibitors known to inhibit the activity of renal angiotensinases (EDTA, diisopropyl phosphorofluoridate and 2,3-dimercaptopropanol) decreased the level of 'angiotensin I immunoreactive material' in kidney fractions treated by radioimmunoassay. By paper chromatography it was apparent that subcellular fractions were capable of degrading 125I-labelled angiotensin I used as tracer in the radioimmunoassay. The degree of degradation followed the distribution of lysosomes among the fractions and was decreased by the angiotensinase inhibitors. The apparent molecular weight of the major portion of angiotensinase activity persisting despite the presence of angiotensinase inhibitors was 75,000, a value similar to that of 'angiotensin immunoreactive material'inkidney fractions treated with non-ionic detergent. On the basis of the present findings it is suggested that 'angiotensin immunoreactive material' may be largely artifactual, beingcreated by the hydrolysis of tracer by angiotensinase enzymes during radioimmunoassay to form fragments that are no longer capable of binding to the specific antibody. This would produced results that would appear the same as those produced had genuine angiotensin immunoreactivity indeed been present in the samples. Such an effect could, in principle, occur in any competitive protein binding assay and should be tested.", "contents": "Identification of \"angiotensin immunoreactive material\" in rat kidney. The reported presence of large quantities of a high molecular weight form of angiotensin I and II in renin granules from rat kidney cortex was investigated. Subcellular fractionation by differential centrifugation and isopycnic gradient centrifugation confirmed the presence of 'angiotensin I immunoreactive material,' but the distribution resembled that of lysosomes rather than renin granules, mitochondria or protein. The material did not possess pressor properties, was stable to incubation at 37 C and was precipitated by ethanol. Incubation of subcellular fractions with peptidase inhibitors known to inhibit the activity of renal angiotensinases (EDTA, diisopropyl phosphorofluoridate and 2,3-dimercaptopropanol) decreased the level of 'angiotensin I immunoreactive material' in kidney fractions treated by radioimmunoassay. By paper chromatography it was apparent that subcellular fractions were capable of degrading 125I-labelled angiotensin I used as tracer in the radioimmunoassay. The degree of degradation followed the distribution of lysosomes among the fractions and was decreased by the angiotensinase inhibitors. The apparent molecular weight of the major portion of angiotensinase activity persisting despite the presence of angiotensinase inhibitors was 75,000, a value similar to that of 'angiotensin immunoreactive material'inkidney fractions treated with non-ionic detergent. On the basis of the present findings it is suggested that 'angiotensin immunoreactive material' may be largely artifactual, beingcreated by the hydrolysis of tracer by angiotensinase enzymes during radioimmunoassay to form fragments that are no longer capable of binding to the specific antibody. This would produced results that would appear the same as those produced had genuine angiotensin immunoreactivity indeed been present in the samples. Such an effect could, in principle, occur in any competitive protein binding assay and should be tested."}
{"id": "PMID:191246", "title": "Effects of biogenic amines on the formation of adenosine 3', 5'-monophosphate in human thyroid slices.", "content": "The effects of various concentrations of biogenic amines on the formation of adenosine-3', 5'-monophosphate (cyclic AMP) and their interactions with other thyroid stimulators were investigated in human thyroid slices from normal and Graves' disease. Most of biogenic amines were found to have the stimulatory effects to some extent. Among the biogenic amines tested, histamine was the most potent thyroid stimulator, norepinephrine and serotonin, the intermediate in terms of cyclic AMP formation. The effect of histamine was almost as potent as TSH in thyroid slices from Graves' disease. This stimulatory effect of histamine was blocked by metiamide, a histamine H2-receptor antagonist, but not by chlorpheniramine, a histamine H1-receptor antagonist. The effect of norepinephrine was completely inhibitied by propranolol, but not by phentolamine. Polyphloretin phosphate did not inhibit norepinephrine- or histamine-induced cyclic AMP formation, while it significantly depressed cyclic AMP formation induced by prostaglandin E2. The maximal effect of histamine was additive to that of TSH. It is suggested that biogenic amines, histamine and norepinephrine, in particular, have the thyroid receptors different from that of TSH or prostaglandin E2 and could play an important role in thyroid physiology.", "contents": "Effects of biogenic amines on the formation of adenosine 3', 5'-monophosphate in human thyroid slices. The effects of various concentrations of biogenic amines on the formation of adenosine-3', 5'-monophosphate (cyclic AMP) and their interactions with other thyroid stimulators were investigated in human thyroid slices from normal and Graves' disease. Most of biogenic amines were found to have the stimulatory effects to some extent. Among the biogenic amines tested, histamine was the most potent thyroid stimulator, norepinephrine and serotonin, the intermediate in terms of cyclic AMP formation. The effect of histamine was almost as potent as TSH in thyroid slices from Graves' disease. This stimulatory effect of histamine was blocked by metiamide, a histamine H2-receptor antagonist, but not by chlorpheniramine, a histamine H1-receptor antagonist. The effect of norepinephrine was completely inhibitied by propranolol, but not by phentolamine. Polyphloretin phosphate did not inhibit norepinephrine- or histamine-induced cyclic AMP formation, while it significantly depressed cyclic AMP formation induced by prostaglandin E2. The maximal effect of histamine was additive to that of TSH. It is suggested that biogenic amines, histamine and norepinephrine, in particular, have the thyroid receptors different from that of TSH or prostaglandin E2 and could play an important role in thyroid physiology."}
{"id": "PMID:191247", "title": "Effects of concanavalin A and neuraminidase on cyclic AMP levels and 14C-1-glucose oxidation in dog thyroid slices.", "content": "Treatment with concanavalin A at 100 micron/ml or higher concentrations significantly increased 14C-1-glucose oxidation in dog thyroid slices as reported in other tissues. This treatment exerted no effect on tissue cyclic AMP levels. Neuraminidase at the same concentrations also had similar effects on these parameters. Neither concanavalin A nor neuraminidase at the concentrations up to 100 microng/ml had the TSH effect on both tissue cyclic AMP and 14C-1-glucose oxidation. These results indicate that modification of carbohydrate moieties of glycoproteins on the cell surface may cause an increase in glucose metabolism without any critical effect on cyclic AMP system and in the process of TSH response.", "contents": "Effects of concanavalin A and neuraminidase on cyclic AMP levels and 14C-1-glucose oxidation in dog thyroid slices. Treatment with concanavalin A at 100 micron/ml or higher concentrations significantly increased 14C-1-glucose oxidation in dog thyroid slices as reported in other tissues. This treatment exerted no effect on tissue cyclic AMP levels. Neuraminidase at the same concentrations also had similar effects on these parameters. Neither concanavalin A nor neuraminidase at the concentrations up to 100 microng/ml had the TSH effect on both tissue cyclic AMP and 14C-1-glucose oxidation. These results indicate that modification of carbohydrate moieties of glycoproteins on the cell surface may cause an increase in glucose metabolism without any critical effect on cyclic AMP system and in the process of TSH response."}
{"id": "PMID:191248", "title": "Hypothalamic pituitary adrenal function in patients with anorexia nervosa.", "content": "Hypothalamic pituitary adrenal function was studied in 14 patients with anorexia nervosa. Although basal plasma cortisol levels in the morning were elevated in most cases, basal plasma ACTH levels were not suppressed. Oral administration of 1 mg dexamethasone 10 hr before blood sampling failed to suppress plasma ACTH and cortisol levels in most patients with anorexia nervosa. Apparent biological half-life of exogenous cortisol was prolonged in all 4 patients with anorexia nervosa tested. The cortisol response to insulin-induced hypoglycemia and exogenous ACTH appeared to be blunted in these patients. It is concluded that anorexia nervosa has dysfunctions of hypothalamic pituitary adrenal axis, especially an abnormal feedback mechanism on ACTH secretion.", "contents": "Hypothalamic pituitary adrenal function in patients with anorexia nervosa. Hypothalamic pituitary adrenal function was studied in 14 patients with anorexia nervosa. Although basal plasma cortisol levels in the morning were elevated in most cases, basal plasma ACTH levels were not suppressed. Oral administration of 1 mg dexamethasone 10 hr before blood sampling failed to suppress plasma ACTH and cortisol levels in most patients with anorexia nervosa. Apparent biological half-life of exogenous cortisol was prolonged in all 4 patients with anorexia nervosa tested. The cortisol response to insulin-induced hypoglycemia and exogenous ACTH appeared to be blunted in these patients. It is concluded that anorexia nervosa has dysfunctions of hypothalamic pituitary adrenal axis, especially an abnormal feedback mechanism on ACTH secretion."}
{"id": "PMID:191249", "title": "Binding of mouse choriomammotropin to prolactin receptors in the mouse mammary gland.", "content": "The interaction between mouse choriomammotropin and mouse mammary glands was examined by radioreceptor assays using ovine prolactin (NIH-P-S9) iodinated by lactoperoxidase as a tracer. Mouse pituitary extracts and placental extracts were subjected to 10% acrylamide gel electrophoresis. Gels were cut into 2-mm segments after electrophoresis, and stored in 1 ml 0.05 M phosphate buffer (pH 7.4) containing 0.05 M NaCl overnight for elution. Lactating mammary tissues from D strain mice were incubated for 120 min in 1 ml Medium 199 containing 6 ng of 125I-prolactin and 0.1 ml of each eluate. Pituitary extracts displaced 125I-prolactin only at the position which coincides with the prolactin band. Displacement was observed at two positions of the gel when placental extracts were used. Relative mobilities (Rm) were 0.21 and 0.71, respectively. The slowly migrating component of choriomammotropin inhibited the binding of 125-I-prolactin more strongly that the rapidly migrating one. Neither of them was identified as a distinct band in stained gels. The molecular weight of ovine prolactin, mouse pituitary prolactin and the slowly migrating component of mouse choriomammotropin was estimated to be 23000 using disc electrophoresis but the ion charges of these hormones were considerably different.", "contents": "Binding of mouse choriomammotropin to prolactin receptors in the mouse mammary gland. The interaction between mouse choriomammotropin and mouse mammary glands was examined by radioreceptor assays using ovine prolactin (NIH-P-S9) iodinated by lactoperoxidase as a tracer. Mouse pituitary extracts and placental extracts were subjected to 10% acrylamide gel electrophoresis. Gels were cut into 2-mm segments after electrophoresis, and stored in 1 ml 0.05 M phosphate buffer (pH 7.4) containing 0.05 M NaCl overnight for elution. Lactating mammary tissues from D strain mice were incubated for 120 min in 1 ml Medium 199 containing 6 ng of 125I-prolactin and 0.1 ml of each eluate. Pituitary extracts displaced 125I-prolactin only at the position which coincides with the prolactin band. Displacement was observed at two positions of the gel when placental extracts were used. Relative mobilities (Rm) were 0.21 and 0.71, respectively. The slowly migrating component of choriomammotropin inhibited the binding of 125-I-prolactin more strongly that the rapidly migrating one. Neither of them was identified as a distinct band in stained gels. The molecular weight of ovine prolactin, mouse pituitary prolactin and the slowly migrating component of mouse choriomammotropin was estimated to be 23000 using disc electrophoresis but the ion charges of these hormones were considerably different."}
{"id": "PMID:191250", "title": "Plasma human calcitonin (hCT) levels in normal and pathologic conditions, and their responses to short calcium or tetragastrin infusion.", "content": "Plasma hCT levels were less than 50 pg/ml in 50 normal subjects. In 16 patients with medullary carcinoma of the thyroid (MCT), plasma hCT levels were distinctively elevated and they fell significantly after total thyroidectomy, but in 11 of them plasma levels were still high, indicating the presence of metastases. In 74 patients with the other types of malignancy, plasma hCT levels were found to be high in 9 cases (3 oat cell carcinoma of the lung, 4 malignant carcinoids, one malignant pheochromocytoma and one acute myelocytic leukemia). Except for the leukemic case, all these tumors were derived from neural crest. In 12 patients with primary hyperparathyroidism, plasma hCT levels were less than 20 pg/ml. In 13 hypoparathyroid patients, two with pseudohypoparathyroidism and one with pseudoidiopathic hypoparathyroidism, plasma hCT levels were slightly elevated. Some patients with uremia had elevated plasma hCT levels, but there was no relation between plasma levels of hCT and those of PTH, urea nitrogen or creatinine. In response to Ca (4.5 mg/kg/10 min) or tetragastrin (4 mug/kg/5 min) infusion, a marked increase in plasma hCT was observed in all patients with MCT, but not in normal subjects. In 5 hypoparathyroid patients, a significant increase to both stimuli was also observed in all cases. Two patients with pseudopseudohypoparathyroidism responded to the Ca load. These results indicate that the determination of plasma hCT levels especially after a short Ca or tetragastrin infusion is important to study various pathological conditions.", "contents": "Plasma human calcitonin (hCT) levels in normal and pathologic conditions, and their responses to short calcium or tetragastrin infusion. Plasma hCT levels were less than 50 pg/ml in 50 normal subjects. In 16 patients with medullary carcinoma of the thyroid (MCT), plasma hCT levels were distinctively elevated and they fell significantly after total thyroidectomy, but in 11 of them plasma levels were still high, indicating the presence of metastases. In 74 patients with the other types of malignancy, plasma hCT levels were found to be high in 9 cases (3 oat cell carcinoma of the lung, 4 malignant carcinoids, one malignant pheochromocytoma and one acute myelocytic leukemia). Except for the leukemic case, all these tumors were derived from neural crest. In 12 patients with primary hyperparathyroidism, plasma hCT levels were less than 20 pg/ml. In 13 hypoparathyroid patients, two with pseudohypoparathyroidism and one with pseudoidiopathic hypoparathyroidism, plasma hCT levels were slightly elevated. Some patients with uremia had elevated plasma hCT levels, but there was no relation between plasma levels of hCT and those of PTH, urea nitrogen or creatinine. In response to Ca (4.5 mg/kg/10 min) or tetragastrin (4 mug/kg/5 min) infusion, a marked increase in plasma hCT was observed in all patients with MCT, but not in normal subjects. In 5 hypoparathyroid patients, a significant increase to both stimuli was also observed in all cases. Two patients with pseudopseudohypoparathyroidism responded to the Ca load. These results indicate that the determination of plasma hCT levels especially after a short Ca or tetragastrin infusion is important to study various pathological conditions."}
{"id": "PMID:191252", "title": "Use of affinity elution chromatography for the microassay of adenosine 3':5'-monophosphate.", "content": "Using the principle of affinity elution chromatography, a microassay has been developed for the determination of picomolar and even smaller quantities of adenosine 3'.5' -monophosphate (cyclic AMP) in biological samples. In principle, cyclic AMP along with the other anions is adsorbed onto an anion exchange cellulose and subsequently, the cyclic nucleotide is specifically eluted with cyclic-AMP -dependent protein kinase. In the actual assay cyclic AMP is determined by competitive displacement of radiolabelled cyclic AMP by non-labelled cyclic nucleotide. The described procedure results in a linear dependence for the displacement of the radioactive nucleotide on cyclic AMP concentration and obviates the usual procedure of sample enrichment by lyophilization. The degree of interference of different nucleotides including cyclic GMP was found to be minimal and in this respect the use affinity elution chromatography was comparable to radioimmunoassay.", "contents": "Use of affinity elution chromatography for the microassay of adenosine 3':5'-monophosphate. Using the principle of affinity elution chromatography, a microassay has been developed for the determination of picomolar and even smaller quantities of adenosine 3'.5' -monophosphate (cyclic AMP) in biological samples. In principle, cyclic AMP along with the other anions is adsorbed onto an anion exchange cellulose and subsequently, the cyclic nucleotide is specifically eluted with cyclic-AMP -dependent protein kinase. In the actual assay cyclic AMP is determined by competitive displacement of radiolabelled cyclic AMP by non-labelled cyclic nucleotide. The described procedure results in a linear dependence for the displacement of the radioactive nucleotide on cyclic AMP concentration and obviates the usual procedure of sample enrichment by lyophilization. The degree of interference of different nucleotides including cyclic GMP was found to be minimal and in this respect the use affinity elution chromatography was comparable to radioimmunoassay."}
{"id": "PMID:191253", "title": "Calf-ovary protein kinases dependent on adenosine 3':5' -monophosphate. Analysis by electrophoresis and electro-focusing on polyacrylamide get.", "content": "High resolving power and quantitative application polyacrylamide-gel electrophopresis at various pore sizes and electrofocusing provide resolution of a calf-ovarian protein-kinase system at an increased level of magnification, as well as optimal preparative routes. Three protein kinases dependent on adenosine 3':5' -monophosphate are distinguished by polyacrylamide gel electrophoresis in calf ovarian cytosol. These enzymes which are observed in the pH range 7.5--10.2, appear to be aggregates of a commonsubmit or monomer. The three kinases are, by the criteria of polyacylamide gel electrophoresis, distinct from three adenosine-3':5' -monophosphate-binding proteins found in the calf ovarian system. Analysis by electrofocusing on polyacrylamide gel shows that conventionally purified preparations of the major kinase of cytosol contain an overwhelming majority of contaminant proteins.", "contents": "Calf-ovary protein kinases dependent on adenosine 3':5' -monophosphate. Analysis by electrophoresis and electro-focusing on polyacrylamide get. High resolving power and quantitative application polyacrylamide-gel electrophopresis at various pore sizes and electrofocusing provide resolution of a calf-ovarian protein-kinase system at an increased level of magnification, as well as optimal preparative routes. Three protein kinases dependent on adenosine 3':5' -monophosphate are distinguished by polyacrylamide gel electrophoresis in calf ovarian cytosol. These enzymes which are observed in the pH range 7.5--10.2, appear to be aggregates of a commonsubmit or monomer. The three kinases are, by the criteria of polyacylamide gel electrophoresis, distinct from three adenosine-3':5' -monophosphate-binding proteins found in the calf ovarian system. Analysis by electrofocusing on polyacrylamide gel shows that conventionally purified preparations of the major kinase of cytosol contain an overwhelming majority of contaminant proteins."}
{"id": "PMID:191254", "title": "Nucleotide sequence of a region in 23-S RNA adjacent to peptidyl transferase catalytic center of Escherichia coli ribosomes.", "content": "N-Iodoacetylphenylalanyl-tRNAPhe was used as an affinity label to localize the RNA components intimately involved in the catalytic center of Escherichia coli ribosomes. This analogue could alkylate the specific region of 23-S RNA that waslocated within 2000 nucleotides from the 3' terminus of the molecule. Sequence analysis revealed that the alkylation by the active substrate (N-iodoacetylphenylalanyl-tRNAPhe) was directed to 5'-terminal adenosine residue of a heptanucleotide, A-U-U-U-U-A-Gp, which seemed to be derived from a heptadecanucleotide, U-U-A-A-A-A-A-C-A-C-A-U-U-U-U-A-Gp, in the original 23-S RNA. The significance of the unique sequence in the ribosomal functions is discussed.", "contents": "Nucleotide sequence of a region in 23-S RNA adjacent to peptidyl transferase catalytic center of Escherichia coli ribosomes. N-Iodoacetylphenylalanyl-tRNAPhe was used as an affinity label to localize the RNA components intimately involved in the catalytic center of Escherichia coli ribosomes. This analogue could alkylate the specific region of 23-S RNA that waslocated within 2000 nucleotides from the 3' terminus of the molecule. Sequence analysis revealed that the alkylation by the active substrate (N-iodoacetylphenylalanyl-tRNAPhe) was directed to 5'-terminal adenosine residue of a heptanucleotide, A-U-U-U-U-A-Gp, which seemed to be derived from a heptadecanucleotide, U-U-A-A-A-A-A-C-A-C-A-U-U-U-U-A-Gp, in the original 23-S RNA. The significance of the unique sequence in the ribosomal functions is discussed."}
{"id": "PMID:191255", "title": "Prolyl 3-hydroxylase: partial characterization of the enzyme from rat kidney cortex.", "content": "The formation of 3-hydroxyproline was studied with crude rat kidney cortex extract as a source of enzyme and chick embryo tendon protocollagen and procollagen or cartilage protocollagen as a substrate. Synthesis of 3-hydroxyproline was observed with all these substrates and the formation of 3-hydroxyproline ranged up to seven residues per pro-alpha-chain. The highest rate of 3-hydroxylation took place at 20 degrees C and the reaction required Fe2+, O2,2-oxoglutarate and ascorbate. The formation of 3-hydroxyproline was affected by chain length and the conformation of the substrate, in that longer polypeptide chains proved better substrates, while the native triple-helical conformation of protocollagen or procollagen completely prevented the reaction. Formation of 3-hydroxyproline with tendon procollagen as a substrate was not inhibited by antiserum to prolyl 4-hydroxylase or by poly(L-proline) when these substances were used in concentrations which clearly inhibited 4-hydroxyproline formation with tendon protocollagen as a substrate. Furthermore, pure prolyl 4-hydroxylase did not synthesize any 3-hydroxyproline under conditions in which the crude rat kidney cortex enzyme would readily do so. The data thus strongly suggest that prolyl 3-hydroxylase and prolyl 4-hydroxylase are separate enzymes.", "contents": "Prolyl 3-hydroxylase: partial characterization of the enzyme from rat kidney cortex. The formation of 3-hydroxyproline was studied with crude rat kidney cortex extract as a source of enzyme and chick embryo tendon protocollagen and procollagen or cartilage protocollagen as a substrate. Synthesis of 3-hydroxyproline was observed with all these substrates and the formation of 3-hydroxyproline ranged up to seven residues per pro-alpha-chain. The highest rate of 3-hydroxylation took place at 20 degrees C and the reaction required Fe2+, O2,2-oxoglutarate and ascorbate. The formation of 3-hydroxyproline was affected by chain length and the conformation of the substrate, in that longer polypeptide chains proved better substrates, while the native triple-helical conformation of protocollagen or procollagen completely prevented the reaction. Formation of 3-hydroxyproline with tendon procollagen as a substrate was not inhibited by antiserum to prolyl 4-hydroxylase or by poly(L-proline) when these substances were used in concentrations which clearly inhibited 4-hydroxyproline formation with tendon protocollagen as a substrate. Furthermore, pure prolyl 4-hydroxylase did not synthesize any 3-hydroxyproline under conditions in which the crude rat kidney cortex enzyme would readily do so. The data thus strongly suggest that prolyl 3-hydroxylase and prolyl 4-hydroxylase are separate enzymes."}
{"id": "PMID:191256", "title": "Physicochemical properties of T4 polynucleotide kinase.", "content": "Some physicochemical properties of T4 polynucleotide kinase (EC2.7.1.78) have been studied. The enzyme is an oligomer of one polypeptide chain. The molecular weight of the monomer is 33000, as determined from the amino acid analysis. Phenylalanine is the N-terminal amino acid. Each monomer contains two --SH groups, one exposed and one more buried. Circular dichroic spectra suggest a high content of alpha-helical structure, 45--55%. Excitation at 280 nm gave a strong emission fluorescence spectrum with a maximum centering at 340 nm. Sedimentation studies suggested the enzymically active form to be a tetramer. High ionic strength (0.1 M KC1), spermine, and the substrates ATP and thymidine 3'-monophosphate were found to be essential factors in order to stabilize the protein in an oligomeric structure. The association constants for ATP, thymidine 3'-monphosphate, and P1 were determined fluorimetrically to be 7.9 x 105, 4.8 x 105, and 7.2 x 10(2) M-1 respectively.", "contents": "Physicochemical properties of T4 polynucleotide kinase. Some physicochemical properties of T4 polynucleotide kinase (EC2.7.1.78) have been studied. The enzyme is an oligomer of one polypeptide chain. The molecular weight of the monomer is 33000, as determined from the amino acid analysis. Phenylalanine is the N-terminal amino acid. Each monomer contains two --SH groups, one exposed and one more buried. Circular dichroic spectra suggest a high content of alpha-helical structure, 45--55%. Excitation at 280 nm gave a strong emission fluorescence spectrum with a maximum centering at 340 nm. Sedimentation studies suggested the enzymically active form to be a tetramer. High ionic strength (0.1 M KC1), spermine, and the substrates ATP and thymidine 3'-monophosphate were found to be essential factors in order to stabilize the protein in an oligomeric structure. The association constants for ATP, thymidine 3'-monphosphate, and P1 were determined fluorimetrically to be 7.9 x 105, 4.8 x 105, and 7.2 x 10(2) M-1 respectively."}
{"id": "PMID:191257", "title": "Thyrotropin stimulation of the phosphorylation of serine in the N-terminal of thyroid H1 histones.", "content": "The analysis of thyroid nuclear proteins by polyacrylamide gel electrophoresis has demonstrated that thyrotropin and dibutyryl adenosine 3':5'-monophosphate stimulate specifically the phosphorylation of H1 histones in an intact cell system. This effect does not require new protein synthesis and implicates the phosphorylation of secrine residue(s) situated in the N-terminal part of H1 histones.", "contents": "Thyrotropin stimulation of the phosphorylation of serine in the N-terminal of thyroid H1 histones. The analysis of thyroid nuclear proteins by polyacrylamide gel electrophoresis has demonstrated that thyrotropin and dibutyryl adenosine 3':5'-monophosphate stimulate specifically the phosphorylation of H1 histones in an intact cell system. This effect does not require new protein synthesis and implicates the phosphorylation of secrine residue(s) situated in the N-terminal part of H1 histones."}
{"id": "PMID:191258", "title": "Effect of neuraminidase on the chromatographic behaviour of eleven acid hydrolases from human liver and plasma.", "content": "1. The elution profiles of eleven acid hydrolases from human liver and plasma were directly compared using a system whereby a single salt gradient was simultaneously applied to two DEAE-cellulose chromatographic columns. 2. Plasma alpha-L-fucosidase, alpha-mannosidase, alpha-galactosidase and alpha-glucosidase isoenzymes were eluted at higher salt concentrations than the corresponding liver isoenzymes whereasbeta-N-acetylglucosaminidase, beta-galactosidase, beta-glucosidase, exo-1,4-beta-xylosidase and alpha-L-arabinofuranosidase isoenzymes were eluted at lower salt concentrations. The elution profiles of beta-glucuronidase and acid phosphatase weremore complex. 3. After incubation with neuraminidase most plasma hydrolases were eluted at lower salt concentrations, however the elution patterns of beta-glucosidase, beta-xylosidase and acid phosphatase were not altered. 4. Preincubation with neuraminidase had no effect on the elution profiles of six liver hydrolases whereas the major isoenzymes of alpha-mannosidase, beta-galactosidase and alpha-L-arabinofuranosidase were eluted at markedly lower salt concentrations. Liver alpha-fucosidase and alpha-galactosidase were eluted at slightly lower salt concentrations afterincubation with neuraminidase. 5. The results are discussed in relation to thepathogenesis of Mucolipidosis II (I-cell disease), and the synthesis and packaging of lysosomal enzymes.", "contents": "Effect of neuraminidase on the chromatographic behaviour of eleven acid hydrolases from human liver and plasma. 1. The elution profiles of eleven acid hydrolases from human liver and plasma were directly compared using a system whereby a single salt gradient was simultaneously applied to two DEAE-cellulose chromatographic columns. 2. Plasma alpha-L-fucosidase, alpha-mannosidase, alpha-galactosidase and alpha-glucosidase isoenzymes were eluted at higher salt concentrations than the corresponding liver isoenzymes whereasbeta-N-acetylglucosaminidase, beta-galactosidase, beta-glucosidase, exo-1,4-beta-xylosidase and alpha-L-arabinofuranosidase isoenzymes were eluted at lower salt concentrations. The elution profiles of beta-glucuronidase and acid phosphatase weremore complex. 3. After incubation with neuraminidase most plasma hydrolases were eluted at lower salt concentrations, however the elution patterns of beta-glucosidase, beta-xylosidase and acid phosphatase were not altered. 4. Preincubation with neuraminidase had no effect on the elution profiles of six liver hydrolases whereas the major isoenzymes of alpha-mannosidase, beta-galactosidase and alpha-L-arabinofuranosidase were eluted at markedly lower salt concentrations. Liver alpha-fucosidase and alpha-galactosidase were eluted at slightly lower salt concentrations afterincubation with neuraminidase. 5. The results are discussed in relation to thepathogenesis of Mucolipidosis II (I-cell disease), and the synthesis and packaging of lysosomal enzymes."}
{"id": "PMID:191259", "title": "The role of leukocyte subpopulations in the indirect leukocyte adherence inhibition assay in the mammary tumor virus system.", "content": "A modification of the leukocyte adherence inhibition test for the detection of cellular immunologic reactivity of mice to the mammary tumor virus (MTV) has been described. It involves the transfer of the leukocyte adherence inhibition factor (LAIF) produced by spleen cells from immunized animals when cultured with antigen to indicator cells, for which peritoneal exudate cells from normal mice are used. The method proves to be sensitive and highly reproducible. By crude separation of leukocyte subpopulations it became established that for the production of LAIF the following sequence is needed: 1. incubation of adherent cells with MTV;2. transfer of a soluble factor SF1 produced by the adherent cells to T cells; 3. transfer of another soluble factor SF2 released by T cells to the adherent cells.", "contents": "The role of leukocyte subpopulations in the indirect leukocyte adherence inhibition assay in the mammary tumor virus system. A modification of the leukocyte adherence inhibition test for the detection of cellular immunologic reactivity of mice to the mammary tumor virus (MTV) has been described. It involves the transfer of the leukocyte adherence inhibition factor (LAIF) produced by spleen cells from immunized animals when cultured with antigen to indicator cells, for which peritoneal exudate cells from normal mice are used. The method proves to be sensitive and highly reproducible. By crude separation of leukocyte subpopulations it became established that for the production of LAIF the following sequence is needed: 1. incubation of adherent cells with MTV;2. transfer of a soluble factor SF1 produced by the adherent cells to T cells; 3. transfer of another soluble factor SF2 released by T cells to the adherent cells."}
{"id": "PMID:191260", "title": "An involvement of alpha-adrenergic stimulation in exercise-induced hypoglycemia.", "content": "Hypoglycemia developed in fasted rats during forced swimming. This hypoglycemia was mostly abolished by phentolamine, an alpha-adrenolytic agent, or by hexamethonium; was potentiated by propranolol, a beta-adrenolytic agent, of by 5-methoxyindole-2-carboxylic acid, a gluconeogenic inhibitor; and was not affected by anti-insulin serum. The turnover rate of blood glucose estimated from the decay curve of blood [14C]glucose increased significantly during exercise. There was a slight but significantly increase during exercise in the transfer of 3-O-methyl-[14C]glucose into muscle and adipose tissues, when it was corrected for by [3H]mannitol transfer to the same tissues. It is concluded that the alpha-receptor-mediated action of endogenous catecholamine stimulates peripheral glucose utilization leading to hypoglycemia during exercise. The action of alpha- and beta-adrenergic mechanisms, directly on peripheral tissues or via insulin secretion, in fine regulation of blood glucose level is discussed.", "contents": "An involvement of alpha-adrenergic stimulation in exercise-induced hypoglycemia. Hypoglycemia developed in fasted rats during forced swimming. This hypoglycemia was mostly abolished by phentolamine, an alpha-adrenolytic agent, or by hexamethonium; was potentiated by propranolol, a beta-adrenolytic agent, of by 5-methoxyindole-2-carboxylic acid, a gluconeogenic inhibitor; and was not affected by anti-insulin serum. The turnover rate of blood glucose estimated from the decay curve of blood [14C]glucose increased significantly during exercise. There was a slight but significantly increase during exercise in the transfer of 3-O-methyl-[14C]glucose into muscle and adipose tissues, when it was corrected for by [3H]mannitol transfer to the same tissues. It is concluded that the alpha-receptor-mediated action of endogenous catecholamine stimulates peripheral glucose utilization leading to hypoglycemia during exercise. The action of alpha- and beta-adrenergic mechanisms, directly on peripheral tissues or via insulin secretion, in fine regulation of blood glucose level is discussed."}
{"id": "PMID:191261", "title": "Positive dromotropic effect of dibutyryl cyclic adenosine 3',5'-monophosphate on the atrioventricular node.", "content": "The effect of atrioventricular (A-V) conduction of N6-2'-0-dibutyryl cyclic 3',5'-adenosine monophosphate (dibutyryl cyclic AMP) was investigated in comparison with those of norepinephrine, cyclic 3',5'-adenosine monophosphate (cyclic AMP), adenosine-5'-monophosphate (5'-AMP), and adenosine by the use of the isolated, blood-perfused A-V node preparation of the dog. Single injections of dibutyryl cyclic AMP (3-300 micronmol) and norepinephrine (0.1-1 nmol) into the posterior septal artery of the preparation (the upper part of the A-V node is mainly perfused through this artery) produced a dose-dependent decrease in the A-V conduction time. The time to the peak effect and the duration of the effect of dibutyryl cyclic AMP were much longer than with norepinephrine. The positive dromotropic effect of dibutyryl cyclic AMP was resistant to the beta-adrenoceptor blocking action of propranolol. Unlike dibutyryl cyclic AMP, cyclic AMP (above 30 nmol), 5'-AMP and adenosine (above 1 nmol) injected into the posterior septal artery prolonged the A-V conduction time in a dose-dependent manner. The results indicate that dibutyryl cyclic AMP has a mode of action on A-V nodal cells which differs distinctly from that of either norepinephrine or cyclic AMP, 5'-AMP, and adenosine.", "contents": "Positive dromotropic effect of dibutyryl cyclic adenosine 3',5'-monophosphate on the atrioventricular node. The effect of atrioventricular (A-V) conduction of N6-2'-0-dibutyryl cyclic 3',5'-adenosine monophosphate (dibutyryl cyclic AMP) was investigated in comparison with those of norepinephrine, cyclic 3',5'-adenosine monophosphate (cyclic AMP), adenosine-5'-monophosphate (5'-AMP), and adenosine by the use of the isolated, blood-perfused A-V node preparation of the dog. Single injections of dibutyryl cyclic AMP (3-300 micronmol) and norepinephrine (0.1-1 nmol) into the posterior septal artery of the preparation (the upper part of the A-V node is mainly perfused through this artery) produced a dose-dependent decrease in the A-V conduction time. The time to the peak effect and the duration of the effect of dibutyryl cyclic AMP were much longer than with norepinephrine. The positive dromotropic effect of dibutyryl cyclic AMP was resistant to the beta-adrenoceptor blocking action of propranolol. Unlike dibutyryl cyclic AMP, cyclic AMP (above 30 nmol), 5'-AMP and adenosine (above 1 nmol) injected into the posterior septal artery prolonged the A-V conduction time in a dose-dependent manner. The results indicate that dibutyryl cyclic AMP has a mode of action on A-V nodal cells which differs distinctly from that of either norepinephrine or cyclic AMP, 5'-AMP, and adenosine."}
{"id": "PMID:191262", "title": "Ethanol-induced changes in gastric mucosal content of cyclic AMP and ATP in the rat.", "content": "The stomach of urethane-anaesthetised rats was perfused with 10% (v/v) ethanol. At 40 min, the secretion of acid was strongly inhibited and the contents of cyclic AMP and ATP were lowered in the superficial mucosa, but not in whole gastric mucosa. After discontinuation of the ethanol perfusion, the rate of gastric acid output as well as the cyclic AMP and ATP levels recovered. Most of the acid-secreting parietal cells were found in the superficial mucosa where the changes of cyclic AMP and ATP took place. The results suggest that lowering of the mucosal contents of cyclic AMP and ATP may be involved in the ethanol-induced inhibition of the gastric acid output.", "contents": "Ethanol-induced changes in gastric mucosal content of cyclic AMP and ATP in the rat. The stomach of urethane-anaesthetised rats was perfused with 10% (v/v) ethanol. At 40 min, the secretion of acid was strongly inhibited and the contents of cyclic AMP and ATP were lowered in the superficial mucosa, but not in whole gastric mucosa. After discontinuation of the ethanol perfusion, the rate of gastric acid output as well as the cyclic AMP and ATP levels recovered. Most of the acid-secreting parietal cells were found in the superficial mucosa where the changes of cyclic AMP and ATP took place. The results suggest that lowering of the mucosal contents of cyclic AMP and ATP may be involved in the ethanol-induced inhibition of the gastric acid output."}
{"id": "PMID:191263", "title": "Involvement of central alpha-adrenoceptors in the hypotensive and bradycardic effects of (--)-delta 9-trans-tetrahydrocannabinol.", "content": "I.v. administration of (--)-delta9-trans-tetrahydrocannabinol (delta 9-THC) to chloralose-anesthetized cats produced a decrease in blood pressure and heart rate. Studies conducted to investigate the mechanism of these changes revealed that the hypotensive and bradycardic effects of delta 9-THC (0.1 mg/kg, i.v.) could be significantly antagonized following intraventricular (i.v.t.) perfusion with alpha-adrenergic receptor blocking agent phentolamine, while a larger dose of delta 9-THC (0.25 mg/kg, i.v.) still produced significant hypotension and bradycardia. I.v.t. perfusion of phentolamine (100 mug/min for 30 min) caused a fall in blood pressure and heart rate which were reversible and produced blockade of central alpha-adrenergic receptors. These results provide evidence for the involvement of central alpha-adrenergic receptors in the hypotensive and bradycardic actions of delta 9-THC and indicate that other receptor mechanisms may also be involved in mediating these responses observed following administration of delta 9-THC.", "contents": "Involvement of central alpha-adrenoceptors in the hypotensive and bradycardic effects of (--)-delta 9-trans-tetrahydrocannabinol. I.v. administration of (--)-delta9-trans-tetrahydrocannabinol (delta 9-THC) to chloralose-anesthetized cats produced a decrease in blood pressure and heart rate. Studies conducted to investigate the mechanism of these changes revealed that the hypotensive and bradycardic effects of delta 9-THC (0.1 mg/kg, i.v.) could be significantly antagonized following intraventricular (i.v.t.) perfusion with alpha-adrenergic receptor blocking agent phentolamine, while a larger dose of delta 9-THC (0.25 mg/kg, i.v.) still produced significant hypotension and bradycardia. I.v.t. perfusion of phentolamine (100 mug/min for 30 min) caused a fall in blood pressure and heart rate which were reversible and produced blockade of central alpha-adrenergic receptors. These results provide evidence for the involvement of central alpha-adrenergic receptors in the hypotensive and bradycardic actions of delta 9-THC and indicate that other receptor mechanisms may also be involved in mediating these responses observed following administration of delta 9-THC."}
{"id": "PMID:191276", "title": "[Virus-induced autoimmunity phenomena in experimental animals (author's transl)].", "content": "It may happen that the virus infection causes changes of the immunogenicity of the host cells that may theoretically result in disturbances of the \"self-recognition\" of the organism. In this paper we report on the immunization of rabbits by autologous testes cells infected with herpes-virus hominis (HVH) types 1 and 2. In 20 rabbits the excision of one testis was carried out. The testes cells were cultivated in L 15-medium (Leibowitz) and lactalbumine hydrolysate supplemented with 12% autologous serum. The virus strains herpesvirus hominis type 1 (Kupka) and type 2 (US) were passaged three times on autologous testes cells, in order to remove host-foreign proteins out of the envelope. Thereafter, the monolayer cultures grown in Demeter flasks were infected with 15 ml virus suspension containing 10(4) to 10(5) TCID50. For the immunization three antigen preparations were applied: a) Supernatant of virus-infected cell cultures, b) Pellets of the virus-infected cell cultures, c) Pellets of the non-infected cell cultures. Two times at an interval of 3 weeks the animals were immunized by intramuscular and intraperitoneal injections with prepared antigens. Altogether, 20 animals were immunized: 15 rabbits with virus antigen, 5 control animals with non-infected autologous cells. After 28 days, 13 rabbits were bled, the second testis, liver, spleen, and kidneys were taken out. From 7 rabbits, only the second testis was taken out. These animals got a further injection on the 40th day post infectionem, and on the 50th day, they were bled. From the tissue samples, frozen sections were cut, fixed with acetone, and treated with fluorescein isothiocyanate-labelled antirabbit globulin, in order to elicite the tissue-bound antibodies. For histological studies, paraffin sections were stained with hematoxylin and eosin, and with azan, besides the PAS reaction was carried out. The determination of humoral antibodies was done by means of indirect-immunofluorescence antibody technique (IFAT). As antigen, autologous cells grown on slides were used; a part of them was infected with HVH types 1 or 2, while another part was not infected. After immunization with autologous testes cells which were infected with HVH types 1 or 2, histologically homogeneous eosinophilic PAS-positive substances were detected in 14 out of 15 rabbits, mainly in the interstitium of the testes (fig. 2). These substances corresponded to globulin deposits that could be demonstrated by the reaction of labelled antirabbit globulin (fig. 1). The testes sections of thoses 5 rabbits that were injected with noninfected autologous cells, did not react. On the 28th day post infectionem, the antibody levels against virus antigen were found at the degree of 1:32 to 1:1024. Only after the removal of the second testis, there occurred antibodies against autologous testes cells. The immunization conditions exclude the formation of isoantibodies...", "contents": "[Virus-induced autoimmunity phenomena in experimental animals (author's transl)]. It may happen that the virus infection causes changes of the immunogenicity of the host cells that may theoretically result in disturbances of the \"self-recognition\" of the organism. In this paper we report on the immunization of rabbits by autologous testes cells infected with herpes-virus hominis (HVH) types 1 and 2. In 20 rabbits the excision of one testis was carried out. The testes cells were cultivated in L 15-medium (Leibowitz) and lactalbumine hydrolysate supplemented with 12% autologous serum. The virus strains herpesvirus hominis type 1 (Kupka) and type 2 (US) were passaged three times on autologous testes cells, in order to remove host-foreign proteins out of the envelope. Thereafter, the monolayer cultures grown in Demeter flasks were infected with 15 ml virus suspension containing 10(4) to 10(5) TCID50. For the immunization three antigen preparations were applied: a) Supernatant of virus-infected cell cultures, b) Pellets of the virus-infected cell cultures, c) Pellets of the non-infected cell cultures. Two times at an interval of 3 weeks the animals were immunized by intramuscular and intraperitoneal injections with prepared antigens. Altogether, 20 animals were immunized: 15 rabbits with virus antigen, 5 control animals with non-infected autologous cells. After 28 days, 13 rabbits were bled, the second testis, liver, spleen, and kidneys were taken out. From 7 rabbits, only the second testis was taken out. These animals got a further injection on the 40th day post infectionem, and on the 50th day, they were bled. From the tissue samples, frozen sections were cut, fixed with acetone, and treated with fluorescein isothiocyanate-labelled antirabbit globulin, in order to elicite the tissue-bound antibodies. For histological studies, paraffin sections were stained with hematoxylin and eosin, and with azan, besides the PAS reaction was carried out. The determination of humoral antibodies was done by means of indirect-immunofluorescence antibody technique (IFAT). As antigen, autologous cells grown on slides were used; a part of them was infected with HVH types 1 or 2, while another part was not infected. After immunization with autologous testes cells which were infected with HVH types 1 or 2, histologically homogeneous eosinophilic PAS-positive substances were detected in 14 out of 15 rabbits, mainly in the interstitium of the testes (fig. 2). These substances corresponded to globulin deposits that could be demonstrated by the reaction of labelled antirabbit globulin (fig. 1). The testes sections of thoses 5 rabbits that were injected with noninfected autologous cells, did not react. On the 28th day post infectionem, the antibody levels against virus antigen were found at the degree of 1:32 to 1:1024. Only after the removal of the second testis, there occurred antibodies against autologous testes cells. The immunization conditions exclude the formation of isoantibodies..."}
{"id": "PMID:191277", "title": "Changes of the phosphatidylcholine content and the number of synaptic vesicles in relation to the neurohumoral transmission in sympathetic ganglia.", "content": "In sympathetic ganglia stimulated in the presence of HC-3, the reduction in number of synaptic vesicles was observed to be accompanied by a significant decrease of the ganglionic phosphatidylcholine content.", "contents": "Changes of the phosphatidylcholine content and the number of synaptic vesicles in relation to the neurohumoral transmission in sympathetic ganglia. In sympathetic ganglia stimulated in the presence of HC-3, the reduction in number of synaptic vesicles was observed to be accompanied by a significant decrease of the ganglionic phosphatidylcholine content."}
{"id": "PMID:191278", "title": "Effect of prostaglandin E1 on rat gastric motility and cyclic nucleotide content.", "content": "Administration of exogenous prostaglandin E1 resulted in an increase in contractility of rat fundic muscle measured in vivo; a significant decrease in fundic tissue levels of cyclic- adenosine monophosphate and a significant increase in cyclic-guanosine monophosphate.", "contents": "Effect of prostaglandin E1 on rat gastric motility and cyclic nucleotide content. Administration of exogenous prostaglandin E1 resulted in an increase in contractility of rat fundic muscle measured in vivo; a significant decrease in fundic tissue levels of cyclic- adenosine monophosphate and a significant increase in cyclic-guanosine monophosphate."}
{"id": "PMID:191279", "title": "Effects of penfluridol of dopamine-sensitive adenylate cyclase in corpus striatum and substantia nigra of rats.", "content": "Penfluridol, a neuroleptic with diphenylbutyl piperidine structure, blocked the dopamine-sensitive adenylate cyclase in homogenates of corpus striatum and substantia nigra of rats, probably by a competitive antagonism versus dopamine.", "contents": "Effects of penfluridol of dopamine-sensitive adenylate cyclase in corpus striatum and substantia nigra of rats. Penfluridol, a neuroleptic with diphenylbutyl piperidine structure, blocked the dopamine-sensitive adenylate cyclase in homogenates of corpus striatum and substantia nigra of rats, probably by a competitive antagonism versus dopamine."}
{"id": "PMID:191280", "title": "Arabinose nucleoside triphosphates are no inhibitors for DNA-dependent RNA polymerases.", "content": "1-Beta-D-arabinofuranosylcytosine-5' -triphosphate and 9-beta-D-arabinofuranosyladenosine-5' -triphosphate were found to have no inhibitory potency for both mammalian DNA-dependent RNA polymerase II and E. coli DNA-dependent RNA polymerase.", "contents": "Arabinose nucleoside triphosphates are no inhibitors for DNA-dependent RNA polymerases. 1-Beta-D-arabinofuranosylcytosine-5' -triphosphate and 9-beta-D-arabinofuranosyladenosine-5' -triphosphate were found to have no inhibitory potency for both mammalian DNA-dependent RNA polymerase II and E. coli DNA-dependent RNA polymerase."}
{"id": "PMID:191281", "title": "Rosette formation by human T and B lymphocytes in the presence of adrenergic and cholinergic drugs.", "content": "It was shown that adrenergic drugs, which increase the intracellular levels of cAMP, inhibit the rosette formation by T-lymphocytes, but stimulate the rosettes produced by B-lymphocytes. Cholinergic drugs, which increase the levels of cGMP, on the contrary, stimulate the formation of rosettes by T-lymphocytes but inhibit those produced by B-lymphocytes.", "contents": "Rosette formation by human T and B lymphocytes in the presence of adrenergic and cholinergic drugs. It was shown that adrenergic drugs, which increase the intracellular levels of cAMP, inhibit the rosette formation by T-lymphocytes, but stimulate the rosettes produced by B-lymphocytes. Cholinergic drugs, which increase the levels of cGMP, on the contrary, stimulate the formation of rosettes by T-lymphocytes but inhibit those produced by B-lymphocytes."}
{"id": "PMID:191282", "title": "Fluorometric study of interaction between ACTH fragments and bovine adrenocortical membranes.", "content": "Corticotropin 1-24 and [Gly1]corticotropin1-18 amide increased the fluorescence of 1-anilinonaphthalene-8-sulfonate which bound to the bovine adrenocortical membranes. The two ACTH fragments interacted with the protein of the membranes and membranes and increased the net positive charge of the membranes.", "contents": "Fluorometric study of interaction between ACTH fragments and bovine adrenocortical membranes. Corticotropin 1-24 and [Gly1]corticotropin1-18 amide increased the fluorescence of 1-anilinonaphthalene-8-sulfonate which bound to the bovine adrenocortical membranes. The two ACTH fragments interacted with the protein of the membranes and membranes and increased the net positive charge of the membranes."}
{"id": "PMID:191283", "title": "Investigations on the turnover of adrenocortical mitochnodria. VII. Effects of ACTH on the half-life of mitochondria from the zona reticularis of the rat adrenal cortex.", "content": "The half-life of mitochondria from the zona reticularis of the rat adrenal was calculated by determining the radioactivity decay curves of the mitochondrial compartment of 3H-thymidine-injected animals, using autoradiographic methods. ACTH was found to enchance significantly the half-life of the organelles.", "contents": "Investigations on the turnover of adrenocortical mitochnodria. VII. Effects of ACTH on the half-life of mitochondria from the zona reticularis of the rat adrenal cortex. The half-life of mitochondria from the zona reticularis of the rat adrenal was calculated by determining the radioactivity decay curves of the mitochondrial compartment of 3H-thymidine-injected animals, using autoradiographic methods. ACTH was found to enchance significantly the half-life of the organelles."}
{"id": "PMID:191284", "title": "Snake venom action: are enzymes involved in it?", "content": "Enzymes were the first clearly recognized components of snake venoms. When several more were discovered, attempts were made to correlate venom action with enzymic functions. The last few years have seen most successful efforts in the identification, isolation and structrual elucidation of highly toxic polypeptides present in snake venoms, in particular of 'neurotoxins' and membrane-active toxins. Following this development the polypeptides were called the true toxic components and the enzymes lost their previous central position in venom pharmacology. The time, therefore, has come re-evaluate the role of enzymes in the complex interaction between snake and prey. While highly active polypeptides indeed dominate the actionof hydrophiid venoms, they appear to play a lesser role in crotalid venom action as compared with enzyme components. Enzymes are involved in many levels of venom action, e.g. by serving as spreading factors, of by producing very active agents, such as bradykinin and lysolecithins in tissues of preys or predators. Some toxins, e.g. the membrane-active polypeptides appear to participate in the interaction between membrane phospholipids and venom phospholipases. The classical neurotoxin, beta-bungarotoxin, has been recognized as a powerful phospholipase. Several instances are known which indicate that some enzymes potentiate the toxic action of others; the analysis of a single enzyme may, therefore, not fully reveal its biofunction. For 3 enzymes,ophidian L-amino acid oxicase, ATPpyrophosphatase, and acetylcholinesterase, some of the problems pertaining to venom toxicity are discussed.", "contents": "Snake venom action: are enzymes involved in it? Enzymes were the first clearly recognized components of snake venoms. When several more were discovered, attempts were made to correlate venom action with enzymic functions. The last few years have seen most successful efforts in the identification, isolation and structrual elucidation of highly toxic polypeptides present in snake venoms, in particular of 'neurotoxins' and membrane-active toxins. Following this development the polypeptides were called the true toxic components and the enzymes lost their previous central position in venom pharmacology. The time, therefore, has come re-evaluate the role of enzymes in the complex interaction between snake and prey. While highly active polypeptides indeed dominate the actionof hydrophiid venoms, they appear to play a lesser role in crotalid venom action as compared with enzyme components. Enzymes are involved in many levels of venom action, e.g. by serving as spreading factors, of by producing very active agents, such as bradykinin and lysolecithins in tissues of preys or predators. Some toxins, e.g. the membrane-active polypeptides appear to participate in the interaction between membrane phospholipids and venom phospholipases. The classical neurotoxin, beta-bungarotoxin, has been recognized as a powerful phospholipase. Several instances are known which indicate that some enzymes potentiate the toxic action of others; the analysis of a single enzyme may, therefore, not fully reveal its biofunction. For 3 enzymes,ophidian L-amino acid oxicase, ATPpyrophosphatase, and acetylcholinesterase, some of the problems pertaining to venom toxicity are discussed."}
{"id": "PMID:191286", "title": "Cyclic nucleotide levels in the perfused rat heart subjected to hypoxia.", "content": "Isolated rat hearts were subjected to hypoxic perfusion on a recirculating Langendorff apparatus. Following a 30-min-period of aerobic stabilization the hearts were perfused for 30 min with media equilibrated with 84% N2, 12%O2 and 4% CO2. At the end of the hypoxic period myocardial concentrations of cyclic AMP and cyclic GMP were determined by radioimmunoassay. Exposure to hypoxia resulted in a significant increase in cyclic AMP (p less than 0.01) and a decrease in cyclic GMP (p less than 0.05) as compared to hearts perfused for 60 min with media gassed with 96% O2. 4% CO2.", "contents": "Cyclic nucleotide levels in the perfused rat heart subjected to hypoxia. Isolated rat hearts were subjected to hypoxic perfusion on a recirculating Langendorff apparatus. Following a 30-min-period of aerobic stabilization the hearts were perfused for 30 min with media equilibrated with 84% N2, 12%O2 and 4% CO2. At the end of the hypoxic period myocardial concentrations of cyclic AMP and cyclic GMP were determined by radioimmunoassay. Exposure to hypoxia resulted in a significant increase in cyclic AMP (p less than 0.01) and a decrease in cyclic GMP (p less than 0.05) as compared to hearts perfused for 60 min with media gassed with 96% O2. 4% CO2."}
{"id": "PMID:191288", "title": "Stimulation of glucagon and inhibition of insulin secretion evoked from carotid baroreceptors.", "content": "The influence from carotid baroreceptors on portal immuno-reactive glucagon and insulin levels and on arterial plasma glucose concentration was studied in vagotomized cats by sectioning of the sinus nerves. Such a complete elimination of the afferent baroreceptor discharge caused a prompt and pronounced increase in the glucose and glucagon levels, whereas the insulin concentration significantly decreased. The role of vascular barorecptors in the hyperglycemic response to hemorrhage is discussed.", "contents": "Stimulation of glucagon and inhibition of insulin secretion evoked from carotid baroreceptors. The influence from carotid baroreceptors on portal immuno-reactive glucagon and insulin levels and on arterial plasma glucose concentration was studied in vagotomized cats by sectioning of the sinus nerves. Such a complete elimination of the afferent baroreceptor discharge caused a prompt and pronounced increase in the glucose and glucagon levels, whereas the insulin concentration significantly decreased. The role of vascular barorecptors in the hyperglycemic response to hemorrhage is discussed."}
{"id": "PMID:191290", "title": "Effects of TSH and cyclic AMP on the human thyroid cells cultured in a chemically defined medium.", "content": "In a serum-free, chemically defined medium human thyroid cells elongated remarkably and resembled fibroblastic cells. They retained the cyclic AMP response to TSH and the supplement of medium with TSH or dibutyryl cyclic AMP permitted the preservation of epithelial nature by the cells. Cyclic AMP of the cells of epithelial nature was higher than those of fibroblastic appearance.", "contents": "Effects of TSH and cyclic AMP on the human thyroid cells cultured in a chemically defined medium. In a serum-free, chemically defined medium human thyroid cells elongated remarkably and resembled fibroblastic cells. They retained the cyclic AMP response to TSH and the supplement of medium with TSH or dibutyryl cyclic AMP permitted the preservation of epithelial nature by the cells. Cyclic AMP of the cells of epithelial nature was higher than those of fibroblastic appearance."}
{"id": "PMID:191295", "title": "Hepatic alcohol oxidation and its metabolic liability.", "content": "The pathways responsible for ethanol oxidation and the toxic results of its metabolism are reviewed. The predominant pathway for ethanol oxidation at low ethanol concentrations involves alcohol dehydrogenase. However, at high alcohol concentrations, up to 50% of ethanol uptake is 4-methylpyrazole-intensitive. Oxidation of ethanol under these conditions is associated with a change in the steady-stage concentration of catalase-H2O2. Based on recent evidence, we conclude that it is unnecessary to postulate that ethanol is oxidized directly via cytochrome P-450. Acetaldehyde production from ethanol via the microsomal subfraction can be accounted for by the combined activities of catalase-H2O2 and alcohol dehydrogenase. The metabolism of ehtanol via alcohol dehydrogenase produces a marked reduction in the hepatocellular NAD-NADH sytems. This reduction is indirectly responsible for the inhibition of glycolysis, gluconeogenesis, citric acid cycle activity, and fatty acid oxidation and may be related to some of the pathological effects observed following chronic consumption of alcohol. Attempts in inhibit alcohol dehydrogenase with alkylpyrazoles and activate catalase with substrates for peroxisomal H2O2-generating flavoproteins, while successful, may have limited applicability because of the native toxicity of the substrates themselves...", "contents": "Hepatic alcohol oxidation and its metabolic liability. The pathways responsible for ethanol oxidation and the toxic results of its metabolism are reviewed. The predominant pathway for ethanol oxidation at low ethanol concentrations involves alcohol dehydrogenase. However, at high alcohol concentrations, up to 50% of ethanol uptake is 4-methylpyrazole-intensitive. Oxidation of ethanol under these conditions is associated with a change in the steady-stage concentration of catalase-H2O2. Based on recent evidence, we conclude that it is unnecessary to postulate that ethanol is oxidized directly via cytochrome P-450. Acetaldehyde production from ethanol via the microsomal subfraction can be accounted for by the combined activities of catalase-H2O2 and alcohol dehydrogenase. The metabolism of ehtanol via alcohol dehydrogenase produces a marked reduction in the hepatocellular NAD-NADH sytems. This reduction is indirectly responsible for the inhibition of glycolysis, gluconeogenesis, citric acid cycle activity, and fatty acid oxidation and may be related to some of the pathological effects observed following chronic consumption of alcohol. Attempts in inhibit alcohol dehydrogenase with alkylpyrazoles and activate catalase with substrates for peroxisomal H2O2-generating flavoproteins, while successful, may have limited applicability because of the native toxicity of the substrates themselves..."}
{"id": "PMID:191296", "title": "The opposing physiological effects of high pressures and inert gases.", "content": "The physiological effects on mammals of elevated pressures (approximately 100 atmospheres) must be considered in the context of the inert gases breathed. The most striking effect of pressure per se is a central hyperexcitability manifest at first by trembling of the entremities and finally by convulsions. Paralysis and death occur at higher pressures. The primary effects of the inert gases breathed are inert gas narcosis and general anesthesia. The exciting effects of pressure per se and the depressive effects of the inert gases tend to oppose each other. Thus consciousness may be restored to anesthetized mice by raising the pressure, and conversely the threshold pressure that causes convulsions is elevated in the presence of anesthetics. These mutually antagonistic effects can be rationalized in terms of model which proposes that both anesthetics and pressure non-specifically perturb thelipid bilayer regions of neutral membranes. This model is termed the critical volume hypothesis. Anthesthetics dissolve in and expand these lipid bilayer regions, while pressure causes mechanical compression. Expansion leads to anesthesia and compression to convulsions if a critical degree of change is achieved. At elevated partial pressures of inert gas the gas-induced expansion is opposed by the compression of pressure per se. With very insoluble gases, such as helium, this expansion is so small that net compression results and the effects of helium differ little from those of pressure per se. With more soluble gases, such as nitrogen, net expansion results in inert gas narcosis and anesthesia. The critical volume hypothesis enables \"safe\" mixtures of \"expanding\" and \"compressing\" gases to be defined. These enable higher pressures to be better tolerated by mammals.", "contents": "The opposing physiological effects of high pressures and inert gases. The physiological effects on mammals of elevated pressures (approximately 100 atmospheres) must be considered in the context of the inert gases breathed. The most striking effect of pressure per se is a central hyperexcitability manifest at first by trembling of the entremities and finally by convulsions. Paralysis and death occur at higher pressures. The primary effects of the inert gases breathed are inert gas narcosis and general anesthesia. The exciting effects of pressure per se and the depressive effects of the inert gases tend to oppose each other. Thus consciousness may be restored to anesthetized mice by raising the pressure, and conversely the threshold pressure that causes convulsions is elevated in the presence of anesthetics. These mutually antagonistic effects can be rationalized in terms of model which proposes that both anesthetics and pressure non-specifically perturb thelipid bilayer regions of neutral membranes. This model is termed the critical volume hypothesis. Anthesthetics dissolve in and expand these lipid bilayer regions, while pressure causes mechanical compression. Expansion leads to anesthesia and compression to convulsions if a critical degree of change is achieved. At elevated partial pressures of inert gas the gas-induced expansion is opposed by the compression of pressure per se. With very insoluble gases, such as helium, this expansion is so small that net compression results and the effects of helium differ little from those of pressure per se. With more soluble gases, such as nitrogen, net expansion results in inert gas narcosis and anesthesia. The critical volume hypothesis enables \"safe\" mixtures of \"expanding\" and \"compressing\" gases to be defined. These enable higher pressures to be better tolerated by mammals."}
{"id": "PMID:191297", "title": "Nutritional factors in relation to heavy metal toxicants.", "content": "An increased environmental exposure to various toxic heavy metals such as lead, cadmium, or mercury seems to be a fact of 20th-century life. But relatively little attention has been paid to the possible implications of sucy exposure for the nutritional status of humans and animals. This review summarizes the information available concerning the effect of various nutritional factors in resistance to metal toxicants and the effect of heavy metal toxicity on nutritional status. In particular, the following questions are considered: 1) Are there any examples of heavy metal toxicity that are potentiated by a nutritional deficiency? 2) Is there any evidence that nutritional deficiency can be caused by heavy metal toxicity? 3) Is there any proof that heavy metal toxicity can be decreased by an excess intake of nutrients: 4) Is there any proof that heavy metal toxicity can be increased by an excess intake of nutrients? The discussion is focused primarily on studies with animal models but, wherever possible, implications for human health are pointed out.", "contents": "Nutritional factors in relation to heavy metal toxicants. An increased environmental exposure to various toxic heavy metals such as lead, cadmium, or mercury seems to be a fact of 20th-century life. But relatively little attention has been paid to the possible implications of sucy exposure for the nutritional status of humans and animals. This review summarizes the information available concerning the effect of various nutritional factors in resistance to metal toxicants and the effect of heavy metal toxicity on nutritional status. In particular, the following questions are considered: 1) Are there any examples of heavy metal toxicity that are potentiated by a nutritional deficiency? 2) Is there any evidence that nutritional deficiency can be caused by heavy metal toxicity? 3) Is there any proof that heavy metal toxicity can be decreased by an excess intake of nutrients: 4) Is there any proof that heavy metal toxicity can be increased by an excess intake of nutrients? The discussion is focused primarily on studies with animal models but, wherever possible, implications for human health are pointed out."}
{"id": "PMID:191298", "title": "The angiotensin I converting enzyme.", "content": "The angiotensin I converting enzyme (kininase II; peptidyl dipeptidase; EC3.4.15.1) has a dual function: it converts angiotensin I to angiotensin II and it inactivates bradykinin. Lung, kidney, guinea pig plasma and testicles are among the richest sources of the enzyme. Vascular endothelial cells and bursh borders of renal proximal tubular cells contain high concentrations of the enzyme. The availability of synthetic peptide inhibitors was a great help in establishing the function of converting enzyme in normal and pathological conditions.", "contents": "The angiotensin I converting enzyme. The angiotensin I converting enzyme (kininase II; peptidyl dipeptidase; EC3.4.15.1) has a dual function: it converts angiotensin I to angiotensin II and it inactivates bradykinin. Lung, kidney, guinea pig plasma and testicles are among the richest sources of the enzyme. Vascular endothelial cells and bursh borders of renal proximal tubular cells contain high concentrations of the enzyme. The availability of synthetic peptide inhibitors was a great help in establishing the function of converting enzyme in normal and pathological conditions."}
{"id": "PMID:191299", "title": "The renin-angiotensin system and the central nervous system.", "content": "One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons in the brain merits investigation.", "contents": "The renin-angiotensin system and the central nervous system. One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons in the brain merits investigation."}
{"id": "PMID:191300", "title": "Blockade of renin or angiotensin for understanding human hypertension: a comparison of propranolol, saralasin and converting enzyme blockade.", "content": "To understand the role of the renin-angiotensin-aldosterone system in the pathogenesis of human hypertension, in serial studies we have blocked the system using three different pharmacologic probes: 1) reduction of renin secretion by administration of the beta receptor blocker, propranolol; 2) blockade of the action of angiotensin II by infusion of saralasin, a competitive antagonist of angiotensin II; and 3) blockade of the enzymatic conversion of angiotensin I to angiotensin II by infusing a nonapeptide competitive inhibitor. The depressor responses induced by either propranolol or the nonapeptide expose a significant to major involvement of excess renin--angiotensin in maintaining the hypertension of some 50 to 70% of common forms of hypertension including \"essential\" hypertension. This subgroup includes nearly all patients with high or \"normal\" renin--sodium profiles. The considerably lower estimates for a renin factor in essential hypertension suggested by saralasin testing now appear due to the partial agonism of this drug. Further studies are required to determine whether this relative or absolute excess of renin secretion is primarily involved in the hypertension and if not why it fails to shut itself off. Similar studies of normal subjects are also needed to determine whether renin support of blood pressure is proportionately greater or less than in hypertensive subjects. Meanwhile the validation provided by these three different pharmacologic probes portends a burgeoning clinical role for renin--sodium profiling not only in screening for renal and adrenal cortical hypertensions but also for characterizing the vasoconstrictor and volume elements involved in various individual patients and thus enabling more specific treatments of the various subtypes of essential hypertension.", "contents": "Blockade of renin or angiotensin for understanding human hypertension: a comparison of propranolol, saralasin and converting enzyme blockade. To understand the role of the renin-angiotensin-aldosterone system in the pathogenesis of human hypertension, in serial studies we have blocked the system using three different pharmacologic probes: 1) reduction of renin secretion by administration of the beta receptor blocker, propranolol; 2) blockade of the action of angiotensin II by infusion of saralasin, a competitive antagonist of angiotensin II; and 3) blockade of the enzymatic conversion of angiotensin I to angiotensin II by infusing a nonapeptide competitive inhibitor. The depressor responses induced by either propranolol or the nonapeptide expose a significant to major involvement of excess renin--angiotensin in maintaining the hypertension of some 50 to 70% of common forms of hypertension including \"essential\" hypertension. This subgroup includes nearly all patients with high or \"normal\" renin--sodium profiles. The considerably lower estimates for a renin factor in essential hypertension suggested by saralasin testing now appear due to the partial agonism of this drug. Further studies are required to determine whether this relative or absolute excess of renin secretion is primarily involved in the hypertension and if not why it fails to shut itself off. Similar studies of normal subjects are also needed to determine whether renin support of blood pressure is proportionately greater or less than in hypertensive subjects. Meanwhile the validation provided by these three different pharmacologic probes portends a burgeoning clinical role for renin--sodium profiling not only in screening for renal and adrenal cortical hypertensions but also for characterizing the vasoconstrictor and volume elements involved in various individual patients and thus enabling more specific treatments of the various subtypes of essential hypertension."}
{"id": "PMID:191303", "title": "[Studies on the thyrotropin receptor in the thyroid: positive cooperativity of Concanavalin A binding and its biphasic effects on thyroid activation induced by thyrotropin (author's transl)].", "content": "Concanavalin A (Con A) was tested for its ability to affect thyroid activation induced by the thyroid stimulators in mouse thyroid tissues. Con A was found to have the biphasic stimulatory and inhibitory effects of thyrotropin (TSH)-induced cyclic AMP formation and endocytosis, a step in thyroid hormone secretion, in mouse thyroid tissues. Low concentrations of Con A potentiated TSH-stimulated cyclic AMP formation and endocytosis. In contrast, high concentrations of Con A markedly inhibited TSH stimulations. These effects were reversed by the addition of methyl-alpha-D-glucoside to the second preincubation medium (without Con A) prior to TSH. A high concentration of Con A alone did not depress the basal levels of cyclic AMP or basal glucose oxidation in thyroid tissues. A high concentration of Con A also inhibited cyclic AMP formation induced by prostaglandin E2 and the long-acting thyroid stimulator (LATS). Binding of 125I-labeled Con A to thyroid tissues increased with time up to 75 min and was very slowly reversible after attainment of equilibrium. Binding was directly proportional to tissue weight. Scatchard plot analysis on the binding of 125I-labeled Con A to thyroid tissues indicated a positive cooperativity which seemed to be well correlated to the biphasic effects.", "contents": "[Studies on the thyrotropin receptor in the thyroid: positive cooperativity of Concanavalin A binding and its biphasic effects on thyroid activation induced by thyrotropin (author's transl)]. Concanavalin A (Con A) was tested for its ability to affect thyroid activation induced by the thyroid stimulators in mouse thyroid tissues. Con A was found to have the biphasic stimulatory and inhibitory effects of thyrotropin (TSH)-induced cyclic AMP formation and endocytosis, a step in thyroid hormone secretion, in mouse thyroid tissues. Low concentrations of Con A potentiated TSH-stimulated cyclic AMP formation and endocytosis. In contrast, high concentrations of Con A markedly inhibited TSH stimulations. These effects were reversed by the addition of methyl-alpha-D-glucoside to the second preincubation medium (without Con A) prior to TSH. A high concentration of Con A alone did not depress the basal levels of cyclic AMP or basal glucose oxidation in thyroid tissues. A high concentration of Con A also inhibited cyclic AMP formation induced by prostaglandin E2 and the long-acting thyroid stimulator (LATS). Binding of 125I-labeled Con A to thyroid tissues increased with time up to 75 min and was very slowly reversible after attainment of equilibrium. Binding was directly proportional to tissue weight. Scatchard plot analysis on the binding of 125I-labeled Con A to thyroid tissues indicated a positive cooperativity which seemed to be well correlated to the biphasic effects."}
{"id": "PMID:191306", "title": "Hepatocarcinogenesis by thioacetamide: correlations of histological and biochemical changes, and possible role of cell injury.", "content": "Hepatocarcinogenesis in rats produced by prolonged feeding of thioacetamide appears as a progressive phenomenon in which morphological changes are associated with important biochemical modifications. It seems most likely that changes in the permeability of cell membrane induced by the carcinogen are responsible for increased intracellular accumulation of Ca2+, and for the ensuring of cell injury produced by Ca2+ overloading of the mitochondria. This calcification of the mitochondria may play a role in the neoplastic transformation of the cell, especially as far as it concerns metabolic behavior and the genetic specification of the permeability characteristics of the transformed cell membrane. The increased synthesis of acid glycosaminoglycans suggests their involvement in calcium-mediated control of tumor development and growth.", "contents": "Hepatocarcinogenesis by thioacetamide: correlations of histological and biochemical changes, and possible role of cell injury. Hepatocarcinogenesis in rats produced by prolonged feeding of thioacetamide appears as a progressive phenomenon in which morphological changes are associated with important biochemical modifications. It seems most likely that changes in the permeability of cell membrane induced by the carcinogen are responsible for increased intracellular accumulation of Ca2+, and for the ensuring of cell injury produced by Ca2+ overloading of the mitochondria. This calcification of the mitochondria may play a role in the neoplastic transformation of the cell, especially as far as it concerns metabolic behavior and the genetic specification of the permeability characteristics of the transformed cell membrane. The increased synthesis of acid glycosaminoglycans suggests their involvement in calcium-mediated control of tumor development and growth."}
{"id": "PMID:191321", "title": "Carcinogenicity of N-nitrosamines related to N-butyl-N-(4-hydroxybutyl)nitrosamine and N,N,-dibutylnitrosamine in ACI/N rats.", "content": "Carcinogenic effect of 14 N-nitrosamines related to N-butyl-N-(4-hydroxybutyl(nitrosamine (BBN) and N,N-dibutylnitrosamine (DBN) was studied in ACI/N male rats by administration in the drinking water. BBN homologs having methyl, ethyl, or pentyl group selectively induced urinary bladder tumors, but a homolog with tert-butyl group did not have any carcinogenic effect. N-Ethyl-N-(3-carboxypropyl)nitrosamine, the principal urinary metabolite of the ethyl homolog of BBN, did also induce bladder tumors selectively, thus providing an additional evidence that N-alkyl-N-(3-carboxypropyl)nitrosamines are responsible for the selective induction of bladder tumors by BBN homologs. N-Butyl-N-(carboxymethyl)nitrosamine and BBN analogs having 3-hydroxypropyl chain together with ethyl or butyl group were found to be noncarcinogenic. N-Propyl-N-butylnitrosamine and DBN induced hepatomas, but simultaneous development of esophageal tumors were observed only with the former. N-Butyl-N-(3-hydroxybutyl)nitrosamine, one of the principal metabolities of DNB, did not induce any  tumors, but its further transformation product, N-butyl-N-(3-oxobutyl)nitrosamine as well as N-butyl-N-(2-oxobutyl)nitrosamine, another metabolic intermediate of DBN, induced hepatomas. Possible correlation of structure and metabolism with organotropic carcinogenesis by N-N-dialkylnitrosamines is discussed, with special reference to selective induction of urinary bladder tumors.", "contents": "Carcinogenicity of N-nitrosamines related to N-butyl-N-(4-hydroxybutyl)nitrosamine and N,N,-dibutylnitrosamine in ACI/N rats. Carcinogenic effect of 14 N-nitrosamines related to N-butyl-N-(4-hydroxybutyl(nitrosamine (BBN) and N,N-dibutylnitrosamine (DBN) was studied in ACI/N male rats by administration in the drinking water. BBN homologs having methyl, ethyl, or pentyl group selectively induced urinary bladder tumors, but a homolog with tert-butyl group did not have any carcinogenic effect. N-Ethyl-N-(3-carboxypropyl)nitrosamine, the principal urinary metabolite of the ethyl homolog of BBN, did also induce bladder tumors selectively, thus providing an additional evidence that N-alkyl-N-(3-carboxypropyl)nitrosamines are responsible for the selective induction of bladder tumors by BBN homologs. N-Butyl-N-(carboxymethyl)nitrosamine and BBN analogs having 3-hydroxypropyl chain together with ethyl or butyl group were found to be noncarcinogenic. N-Propyl-N-butylnitrosamine and DBN induced hepatomas, but simultaneous development of esophageal tumors were observed only with the former. N-Butyl-N-(3-hydroxybutyl)nitrosamine, one of the principal metabolities of DNB, did not induce any  tumors, but its further transformation product, N-butyl-N-(3-oxobutyl)nitrosamine as well as N-butyl-N-(2-oxobutyl)nitrosamine, another metabolic intermediate of DBN, induced hepatomas. Possible correlation of structure and metabolism with organotropic carcinogenesis by N-N-dialkylnitrosamines is discussed, with special reference to selective induction of urinary bladder tumors."}
{"id": "PMID:191322", "title": "Effect of sulfated polysaccharides on blood-borne pulmonary metastasis in rats.", "content": "The inhibitory effect of sulfated polysaccharides on blood-borne metastasis was examined. As a model of blood-borne metastasis, the ascitic form of hepatoma AH-109A tumor was injected intravenously into Donryu strain rats. Examination of the pulmonary metastatic nodules developed 2 weeks later showed inhibitory effect of the five sulfated polysaccharides tested. Xylan sulfate was the most inhibitory, and exerted its inhibitory effect when the tumor cells were in the pulmonary capillary beds. However, fromthe rapid disappearance of radioactivity from the lungs after injection of 125IUDR-labeled AH-109A cells, tumor cells seemed to be retained in the lungs for only a very short time. Measurement of the anticoagulative and fibrinolytic activities of three sulfated polysaccharides showed that the inhibitory effect of these compounds on blood-borne metastasis was proportional to their anticoagulative and fibrinolytic activities, xylan sulfate showing the highest activities. These results suggest that sulfated polyaccharides may inhibit blood-borne pulmonary metastasis by inhibiting the lodging of tumor cells in the pulmonary capillary beds.", "contents": "Effect of sulfated polysaccharides on blood-borne pulmonary metastasis in rats. The inhibitory effect of sulfated polysaccharides on blood-borne metastasis was examined. As a model of blood-borne metastasis, the ascitic form of hepatoma AH-109A tumor was injected intravenously into Donryu strain rats. Examination of the pulmonary metastatic nodules developed 2 weeks later showed inhibitory effect of the five sulfated polysaccharides tested. Xylan sulfate was the most inhibitory, and exerted its inhibitory effect when the tumor cells were in the pulmonary capillary beds. However, fromthe rapid disappearance of radioactivity from the lungs after injection of 125IUDR-labeled AH-109A cells, tumor cells seemed to be retained in the lungs for only a very short time. Measurement of the anticoagulative and fibrinolytic activities of three sulfated polysaccharides showed that the inhibitory effect of these compounds on blood-borne metastasis was proportional to their anticoagulative and fibrinolytic activities, xylan sulfate showing the highest activities. These results suggest that sulfated polyaccharides may inhibit blood-borne pulmonary metastasis by inhibiting the lodging of tumor cells in the pulmonary capillary beds."}
{"id": "PMID:191323", "title": "Induction of papillary ependymomas and insulinomas in the Syrian golden hamster by BK virus, a human papovavirus.", "content": "Newborn hamsters were inoculated intracerebrally with BK virus. Between 3 and 6 months after inoculation, they developed papillary ependymoma (8 hamsters, 42%) or functional malignant islet cell tumors of the pancreas (insulinoma, 8 hamsters), or both (1 hamster). Both tumors contained an antigen reactive to SV40 T-antibody, suggesting that at least a part of BK virus genomen has been integrated into the tumor cells. No infectious virus was detected in the extract of these tumors.", "contents": "Induction of papillary ependymomas and insulinomas in the Syrian golden hamster by BK virus, a human papovavirus. Newborn hamsters were inoculated intracerebrally with BK virus. Between 3 and 6 months after inoculation, they developed papillary ependymoma (8 hamsters, 42%) or functional malignant islet cell tumors of the pancreas (insulinoma, 8 hamsters), or both (1 hamster). Both tumors contained an antigen reactive to SV40 T-antibody, suggesting that at least a part of BK virus genomen has been integrated into the tumor cells. No infectious virus was detected in the extract of these tumors."}
{"id": "PMID:191324", "title": "Electron microscopic evidence of surface immunoglobulins in Yoshida ascites sarcomas and ascites hepatomas.", "content": "Yoshida ascties sarcoma and its variants and several azo dye-induced ascites hepatomas of rats were examined by an immuno-peroxidase technique to demonstrate surface immunoglobulins. More than 60% of the tumor cells in 8 ascites tumors showed positive surface staining (Group A), whereas the other 9 tumors were less than 15% positive (Group B). One tumor showed 34% positive reaction. The staining did not show capping. Six of the 8 Group-A tumors were single cell type, while 5 of the 9 Group-B tumors were island type. Intravenous transplantation rate was very low (less than 10%) in 2 of the 6 Group-B tumors, but only 1 of the 7 Group-A tumors showed moderately low (40%) intravenous transplantation rate. All of the 8 Group-A tumors showed survival period of less than 35 days after intraperitoneal transplantation, while the survival period was more than 45 days in 3 out of the 9 Group-B tumors.", "contents": "Electron microscopic evidence of surface immunoglobulins in Yoshida ascites sarcomas and ascites hepatomas. Yoshida ascties sarcoma and its variants and several azo dye-induced ascites hepatomas of rats were examined by an immuno-peroxidase technique to demonstrate surface immunoglobulins. More than 60% of the tumor cells in 8 ascites tumors showed positive surface staining (Group A), whereas the other 9 tumors were less than 15% positive (Group B). One tumor showed 34% positive reaction. The staining did not show capping. Six of the 8 Group-A tumors were single cell type, while 5 of the 9 Group-B tumors were island type. Intravenous transplantation rate was very low (less than 10%) in 2 of the 6 Group-B tumors, but only 1 of the 7 Group-A tumors showed moderately low (40%) intravenous transplantation rate. All of the 8 Group-A tumors showed survival period of less than 35 days after intraperitoneal transplantation, while the survival period was more than 45 days in 3 out of the 9 Group-B tumors."}
{"id": "PMID:191325", "title": "Iron incorporation into liver cells and ferritin of tumor-bearing rats.", "content": "Measurement of the incorporation of iron into liver cells and liver ferritin of the rat revealed that both incorporated less iron under tumor-bearing condition than in the normal state.", "contents": "Iron incorporation into liver cells and ferritin of tumor-bearing rats. Measurement of the incorporation of iron into liver cells and liver ferritin of the rat revealed that both incorporated less iron under tumor-bearing condition than in the normal state."}
{"id": "PMID:191326", "title": "Cytochrome P-450 in hyperplastic liver nodules during hepatocarcinogenesis with N-2-fluorenylacetamide in rats.", "content": "Amount of cytochrome P-450 in the hyperplastic liver nodules was measured during hepatocarcinogenesis with N-2-fluorenylacetamide in the rat. Amount of cytochrome P-450 in the liver microsome decreased in early stage of hepatocarcinogenesis. Concentration of cytochrome P-450 in the hyperplastic nodules and their surrounding tissues was examined, using homogenate from each of them. Its amount was significantly less in the hyperplastic nodules in the 13th week than in their surrounding tissues, and became more in hyperplastic nodules in the 19th week. The hyperplastic nodules of the animals treated with phenobarbital showed almost the same amount of cytochrome P-450 as that in the controls. Amount of cytochrome P-450 in hepatoma tissues also showed similar values as that in hyperplastic nodules.", "contents": "Cytochrome P-450 in hyperplastic liver nodules during hepatocarcinogenesis with N-2-fluorenylacetamide in rats. Amount of cytochrome P-450 in the hyperplastic liver nodules was measured during hepatocarcinogenesis with N-2-fluorenylacetamide in the rat. Amount of cytochrome P-450 in the liver microsome decreased in early stage of hepatocarcinogenesis. Concentration of cytochrome P-450 in the hyperplastic nodules and their surrounding tissues was examined, using homogenate from each of them. Its amount was significantly less in the hyperplastic nodules in the 13th week than in their surrounding tissues, and became more in hyperplastic nodules in the 19th week. The hyperplastic nodules of the animals treated with phenobarbital showed almost the same amount of cytochrome P-450 as that in the controls. Amount of cytochrome P-450 in hepatoma tissues also showed similar values as that in hyperplastic nodules."}
{"id": "PMID:191327", "title": "Further observation of Kashara isoenzyme in patients with malignant diseases.", "content": "The Kasahara isoenzyme of alkaline phosphatase was found in cancer tissues from patients with gastric carcinoma, maxillary carcinoma, pulmonary carcinoma, and carcinoma of the urinary bladder, in addition to hepatoma. This fact suggests that the Kasahara isoenzyme may not be a specific marker protein of liver cancer but could occur in a variety of neoplasms.", "contents": "Further observation of Kashara isoenzyme in patients with malignant diseases. The Kasahara isoenzyme of alkaline phosphatase was found in cancer tissues from patients with gastric carcinoma, maxillary carcinoma, pulmonary carcinoma, and carcinoma of the urinary bladder, in addition to hepatoma. This fact suggests that the Kasahara isoenzyme may not be a specific marker protein of liver cancer but could occur in a variety of neoplasms."}
{"id": "PMID:191328", "title": "Squamous carcinoma of the stomach after luetic linitis plastica.", "content": "This report illustrates many of the long term complicatio of syphilis involving the stomach. A 49-year-old woman with diffuse squamous metaplasia of the gastric mucosa developed invasive pure squamous cell carcinoma. The literature is reviewed and the probable pathophysiology is discussed.", "contents": "Squamous carcinoma of the stomach after luetic linitis plastica. This report illustrates many of the long term complicatio of syphilis involving the stomach. A 49-year-old woman with diffuse squamous metaplasia of the gastric mucosa developed invasive pure squamous cell carcinoma. The literature is reviewed and the probable pathophysiology is discussed."}
{"id": "PMID:191331", "title": "Cytochemical studies of rat liver glycogen and alkaline phosphatase under the effect of hepatocarcinogens.", "content": "Cytochemical changes of glycogen and alkaline phosphatase were studied under sequential effect of p-dimethylaminoazobenzene (DAB) feeding and CCl4 injections. It has been found that in liver cells of experimental animals, the concentration of glycogen and the activity of alkaline phosphatase were decreased.", "contents": "Cytochemical studies of rat liver glycogen and alkaline phosphatase under the effect of hepatocarcinogens. Cytochemical changes of glycogen and alkaline phosphatase were studied under sequential effect of p-dimethylaminoazobenzene (DAB) feeding and CCl4 injections. It has been found that in liver cells of experimental animals, the concentration of glycogen and the activity of alkaline phosphatase were decreased."}
{"id": "PMID:191337", "title": "Streptococcal extracellular NAD-glycohydrolase. Optimal temperature and activation by cysteine.", "content": "Streptococcal extracellular NAD-glycohydrolase (EC 3.2.2.5) exists in two distinct states with respect to the optimal reaction temperature. Bacteria produce the enzyme form with optimum activity at about 40 degress C. Probably due to oxygen action, the enzyme is converted to a form with optimum activity at 30 degrees C. Compounds of the type of cysteine restore the initial state. The conversions are accompanied by enzyme activity fluctuations.", "contents": "Streptococcal extracellular NAD-glycohydrolase. Optimal temperature and activation by cysteine. Streptococcal extracellular NAD-glycohydrolase (EC 3.2.2.5) exists in two distinct states with respect to the optimal reaction temperature. Bacteria produce the enzyme form with optimum activity at about 40 degress C. Probably due to oxygen action, the enzyme is converted to a form with optimum activity at 30 degrees C. Compounds of the type of cysteine restore the initial state. The conversions are accompanied by enzyme activity fluctuations."}
{"id": "PMID:191341", "title": "[Burkitt's lymphoma].", "content": "The Burkitt's tumor is a neoplastic disease which occurs mostly in the tropics. Sporadic cases however are distributed all over the world. This undifferentiated lymphosarcoma predominates in children. Extralymphnodal in origin, quick growth and lack of pain are very characteristic signs. Unattended most of the patients die within a few months. Cytostatic treatment in connection with x-ray therapy and surgical proceedings show some results. The Epstein-Barr-virus is incriminated to play a causative role in the pathogenesis of Burkitt's lymphoma. But the experimental proof of its oncogenic activity in human beings has not yet been demonstrated. The problem of an active immunization is to be controlled.", "contents": "[Burkitt's lymphoma]. The Burkitt's tumor is a neoplastic disease which occurs mostly in the tropics. Sporadic cases however are distributed all over the world. This undifferentiated lymphosarcoma predominates in children. Extralymphnodal in origin, quick growth and lack of pain are very characteristic signs. Unattended most of the patients die within a few months. Cytostatic treatment in connection with x-ray therapy and surgical proceedings show some results. The Epstein-Barr-virus is incriminated to play a causative role in the pathogenesis of Burkitt's lymphoma. But the experimental proof of its oncogenic activity in human beings has not yet been demonstrated. The problem of an active immunization is to be controlled."}
{"id": "PMID:191342", "title": "[Wilms tumor in hemihypertrophy].", "content": "The case of a 4-year-old boy with Wilms' tumor and hemihypertrophy is described. Wilms' tumors are frequently associated with congenital malformations of the urinary tract, with aniridia and hemihypertrophy. Hemihypertrophy is a relatively rare malformation (1:14000) in the common population, but in patients with Wilms' tumors its frequency is about 1:49. Besides Wilms' tumors tumors of the adrenal cortex and hepatoblastomas are frequently observed together with hemihypertrophy.", "contents": "[Wilms tumor in hemihypertrophy]. The case of a 4-year-old boy with Wilms' tumor and hemihypertrophy is described. Wilms' tumors are frequently associated with congenital malformations of the urinary tract, with aniridia and hemihypertrophy. Hemihypertrophy is a relatively rare malformation (1:14000) in the common population, but in patients with Wilms' tumors its frequency is about 1:49. Besides Wilms' tumors tumors of the adrenal cortex and hepatoblastomas are frequently observed together with hemihypertrophy."}
{"id": "PMID:191343", "title": "The contribution of hepatic triglyceride lipase to plasma post-heparin lipolytic activity in the rat.", "content": "Plasma post-heparin lipolytic activity (PHLA) was reduced by 50% in functionally hepatectomised compared with shamoperated rats. Inhibition of PHLA by protamine sulphate was significantly increased in functionally hepatectomised compared with shamoperated rats. Hepatic triglyceride lipase contributes significantly to total plasma PHLA. Its function is not yet clear.", "contents": "The contribution of hepatic triglyceride lipase to plasma post-heparin lipolytic activity in the rat. Plasma post-heparin lipolytic activity (PHLA) was reduced by 50% in functionally hepatectomised compared with shamoperated rats. Inhibition of PHLA by protamine sulphate was significantly increased in functionally hepatectomised compared with shamoperated rats. Hepatic triglyceride lipase contributes significantly to total plasma PHLA. Its function is not yet clear."}
{"id": "PMID:191339", "title": "A comparison of the pathogenicity of three strains of bovid herpesvirus 2 in calves.", "content": "The isolates of Bovid herpesvirus 2 share common morphological, physical and antigenic features, but differences in their pathogenicity for cattle have been found among the strains. In order to investigate this aspect in more detail a comparative study was made of the skin lesions produced in calves by three strains of the virus: Allerton BA, bovine mammilitis and 69/1L0. The results show that Allerton BA was less pathogenic for calves than the other two strains used in the experiment. This conclusion is supported by the observations that very few inclusion bodies were found in the lesions produced by Alerton BA, and the maximum titre of virus in the lesions was lower than the titres obtained with bovine mammillitis and 69/1L0. Moreover the thickness and diameter of the lesions with Allerton BA were less than those with the other strains. It is speculated that Allerton BA strain, which originated from a buffalo, might behave similarly to bovine mammillitis and 69/1LO following serial passages in cattle.", "contents": "A comparison of the pathogenicity of three strains of bovid herpesvirus 2 in calves. The isolates of Bovid herpesvirus 2 share common morphological, physical and antigenic features, but differences in their pathogenicity for cattle have been found among the strains. In order to investigate this aspect in more detail a comparative study was made of the skin lesions produced in calves by three strains of the virus: Allerton BA, bovine mammilitis and 69/1L0. The results show that Allerton BA was less pathogenic for calves than the other two strains used in the experiment. This conclusion is supported by the observations that very few inclusion bodies were found in the lesions produced by Alerton BA, and the maximum titre of virus in the lesions was lower than the titres obtained with bovine mammillitis and 69/1L0. Moreover the thickness and diameter of the lesions with Allerton BA were less than those with the other strains. It is speculated that Allerton BA strain, which originated from a buffalo, might behave similarly to bovine mammillitis and 69/1LO following serial passages in cattle."}
{"id": "PMID:191344", "title": "Effects of cyclic AMP and dibutyryl cyclic AMP on amino acid transport in the isolated rat ovary.", "content": "Prepubertal rat ovaries were incubated in medium containing the non-utilizable amino acids alpha-aminoisobutyric acid (AIB-14C) or 1-aminocyclo-pentane-carboxylic acid (cycloleucine-14C). The rate of uptake of the two amino acids was studied in the isolated ovaries after different incubation periods. Addition of 5mM cyclic AMP (cAMP) caused a slight stimulation of the AIB-transport but in higher concentrations (10-25 mM) an inhibition was noted. With dibutyrl cyclic AMP (dbcAMP) a dose-dependent increase was seen with 0.5-5 mM concentrations with no further effect of higher concentrations. Time course studies were performed with both AIB and cycloleucine in presence of 10 mM dbcAMP and increased uptake values were noted at each time studied (30-240 min). The phosphodiesterase inhibitor aminophyline in lower concentrations did not influence AIB-transport but 5-10 mM caused increased uptake values in the ovaries. The stimulatory action of dbcAMP on amino acid transport was augmented by a low concentration of aminophylline (0.5 mM). Experiments were in addition carried out in the presence of puromycin and under these circumstances it was still possible to enhance amino acid transport by addition of dbcAMP. The results are discussed in relation to earlier reported effects of gonadotropins on ovarian amino acid transport.", "contents": "Effects of cyclic AMP and dibutyryl cyclic AMP on amino acid transport in the isolated rat ovary. Prepubertal rat ovaries were incubated in medium containing the non-utilizable amino acids alpha-aminoisobutyric acid (AIB-14C) or 1-aminocyclo-pentane-carboxylic acid (cycloleucine-14C). The rate of uptake of the two amino acids was studied in the isolated ovaries after different incubation periods. Addition of 5mM cyclic AMP (cAMP) caused a slight stimulation of the AIB-transport but in higher concentrations (10-25 mM) an inhibition was noted. With dibutyrl cyclic AMP (dbcAMP) a dose-dependent increase was seen with 0.5-5 mM concentrations with no further effect of higher concentrations. Time course studies were performed with both AIB and cycloleucine in presence of 10 mM dbcAMP and increased uptake values were noted at each time studied (30-240 min). The phosphodiesterase inhibitor aminophyline in lower concentrations did not influence AIB-transport but 5-10 mM caused increased uptake values in the ovaries. The stimulatory action of dbcAMP on amino acid transport was augmented by a low concentration of aminophylline (0.5 mM). Experiments were in addition carried out in the presence of puromycin and under these circumstances it was still possible to enhance amino acid transport by addition of dbcAMP. The results are discussed in relation to earlier reported effects of gonadotropins on ovarian amino acid transport."}
{"id": "PMID:191340", "title": "The gross and histological findings in the liver of pigs with Aujeszky's disease.", "content": "The gross and histological changes were studied in the liver of young pigs naturally infected with Aujeszky's disease. In the majority of the cases examined it was possible to detect small necrotic foci, scattered throughout the liver parenchyma, which corresponded histologically with intralobular or plurilobular areas of coagulative necrosis. At the periphery of the larger necrotic foci, inclusion bodies were also found in the hepatocytes of 9 of the 17 pigs examined. These intranuclear inclusion bodies showed various developmental features, similar to those reported quite frequently in herpesvirus infections of animals.", "contents": "The gross and histological findings in the liver of pigs with Aujeszky's disease. The gross and histological changes were studied in the liver of young pigs naturally infected with Aujeszky's disease. In the majority of the cases examined it was possible to detect small necrotic foci, scattered throughout the liver parenchyma, which corresponded histologically with intralobular or plurilobular areas of coagulative necrosis. At the periphery of the larger necrotic foci, inclusion bodies were also found in the hepatocytes of 9 of the 17 pigs examined. These intranuclear inclusion bodies showed various developmental features, similar to those reported quite frequently in herpesvirus infections of animals."}
{"id": "PMID:191347", "title": "Fine structural studies of a human thyroid adenoma, with special reference to psammoma bodies.", "content": "The fine structural morphologic features of a microfollicular thyroid adenoma from a 28 year old female were examined. Although the patient had been laking exogenous thyroxine therapy for 14 months, the morphology of the adenoma was characterized by numerous small to medium sized follicles composed of metabolically active, well differentiated columnar cells with numerous colloid droplets, dilated granular endoplasmic reticulum, large numbers of coated vesicles and lysosomes, large colloid containing \"lakes,\" microtubules, microfilaments, and prominent apical microvillous projections. Of special inetrest were small spherical psammomatous calcospherites ecountered in histiocytes and the interstitium. Also noteworthy were ropelike configurations observed in most of the follicular lumina. Structural-functional correlations and potential origins of psammoma bodies and calcospherites are discussed.", "contents": "Fine structural studies of a human thyroid adenoma, with special reference to psammoma bodies. The fine structural morphologic features of a microfollicular thyroid adenoma from a 28 year old female were examined. Although the patient had been laking exogenous thyroxine therapy for 14 months, the morphology of the adenoma was characterized by numerous small to medium sized follicles composed of metabolically active, well differentiated columnar cells with numerous colloid droplets, dilated granular endoplasmic reticulum, large numbers of coated vesicles and lysosomes, large colloid containing \"lakes,\" microtubules, microfilaments, and prominent apical microvillous projections. Of special inetrest were small spherical psammomatous calcospherites ecountered in histiocytes and the interstitium. Also noteworthy were ropelike configurations observed in most of the follicular lumina. Structural-functional correlations and potential origins of psammoma bodies and calcospherites are discussed."}
{"id": "PMID:191348", "title": "A new variety of hereditary sensory neuropathy.", "content": "A pedigree with a new form of hereditary sensory neuropathy is described. Ataxia and scoliosis rather than loss of pain and ulcerating acropathy are the principal clinical feature. Analysis of the pedigree suggests a dominant mode of transmission with variable age of onset and perhaps reduced penetrance.", "contents": "A new variety of hereditary sensory neuropathy. A pedigree with a new form of hereditary sensory neuropathy is described. Ataxia and scoliosis rather than loss of pain and ulcerating acropathy are the principal clinical feature. Analysis of the pedigree suggests a dominant mode of transmission with variable age of onset and perhaps reduced penetrance."}
{"id": "PMID:191349", "title": "Evidence for X-linkage of phosphoribosylpyrophosphate synthetase in man. Studies with cultured fibroblasts from a gouty family with mutant feedback-resistant enzyme.", "content": "Skin fibroblast cultures were utilized to study the mode of inheritance of a mutant feedback-resistant phosphoribosylpyrophosphate synthetase in a gouty family with purine overproduction. Selective conditions were applied to allow the survival in culture of mutant cells only. Whereas in the male gouty propositus the cell culture was homogenous for the mutant enzyme, in the cell culture from his nongouty mother two cell populations were demonstrated, one normal and the other mutant. The mosaicism in the mother is compatible with X-linkage of the enzyme. From this finding, together with the clinical and biochemical data available, it is concluded that in this family the enzyme mutation is transmitted in a X-linked recessive pattern.", "contents": "Evidence for X-linkage of phosphoribosylpyrophosphate synthetase in man. Studies with cultured fibroblasts from a gouty family with mutant feedback-resistant enzyme. Skin fibroblast cultures were utilized to study the mode of inheritance of a mutant feedback-resistant phosphoribosylpyrophosphate synthetase in a gouty family with purine overproduction. Selective conditions were applied to allow the survival in culture of mutant cells only. Whereas in the male gouty propositus the cell culture was homogenous for the mutant enzyme, in the cell culture from his nongouty mother two cell populations were demonstrated, one normal and the other mutant. The mosaicism in the mother is compatible with X-linkage of the enzyme. From this finding, together with the clinical and biochemical data available, it is concluded that in this family the enzyme mutation is transmitted in a X-linked recessive pattern."}
{"id": "PMID:191352", "title": "Ultrastructural and immunofluorescent studies of the replication of herpesvirus saimiri in cultured lymphocytes of infected owl monkeys.", "content": "The lymphocytes of five owl monkeys infected with herpesvirus saimiri (HVS) and of three control owl monkeys were studied by electron microscopic (EM) and immunofluorescent (IF) techniques. Buffy coats of whole blood immediately after bleeding were also prepared for study. At the time of the study, two of the five infected monkeys were leukaemic; within 50 days after the study, four of the five had died with malignant lymphoma and lymphocytic leukaemia. HVS virions were demonstrated by EM and HVS antigens by IF in 1-20% of the lymphocytes from infected monkeys in 2/5 cultures at 24 hours AC, 4/5 at 48 hours AC, and 5/5 at 72 hours AC. There was quite good agreement between the EM and IF data. None of the control monkey cultures and none of the buffy coat preparations contained HVS virions or antigens. By EM, the great majority of the virus particles were nucleocapsids within the nuclei of lymphocytes. Enveloped virions were rare. There was some evidence to suggest that the higher the percentage of lymphocytes containing HVS, the poorer the prognosis for the monkey. HVS was isolated from all five infected monkeys by co-cultivation of lymphocytes with Vero cells. Control lymphocyte co-cultivations were negative.", "contents": "Ultrastructural and immunofluorescent studies of the replication of herpesvirus saimiri in cultured lymphocytes of infected owl monkeys. The lymphocytes of five owl monkeys infected with herpesvirus saimiri (HVS) and of three control owl monkeys were studied by electron microscopic (EM) and immunofluorescent (IF) techniques. Buffy coats of whole blood immediately after bleeding were also prepared for study. At the time of the study, two of the five infected monkeys were leukaemic; within 50 days after the study, four of the five had died with malignant lymphoma and lymphocytic leukaemia. HVS virions were demonstrated by EM and HVS antigens by IF in 1-20% of the lymphocytes from infected monkeys in 2/5 cultures at 24 hours AC, 4/5 at 48 hours AC, and 5/5 at 72 hours AC. There was quite good agreement between the EM and IF data. None of the control monkey cultures and none of the buffy coat preparations contained HVS virions or antigens. By EM, the great majority of the virus particles were nucleocapsids within the nuclei of lymphocytes. Enveloped virions were rare. There was some evidence to suggest that the higher the percentage of lymphocytes containing HVS, the poorer the prognosis for the monkey. HVS was isolated from all five infected monkeys by co-cultivation of lymphocytes with Vero cells. Control lymphocyte co-cultivations were negative."}
{"id": "PMID:191357", "title": "Response of marmosets to experimental infection with Epstein-Barr virus.", "content": "The response of cotton-topped (CT) or white-lipped (WL) marmosets, inoculated with material containing Epstein-Barr virus (EBV), was studied. Twenty-five marmosets inoculated with 10(6)-10(8) cells from human or simian EBV-carrying lymphoblastoid cell cultures developed no detectable clinical disease. Transitory antibody titres to VCA were detected in sera from several of these marmosets. Thirty-eight marmosets inoculated with P3 virus (10(9) particles) and seven marmosets inoculated with 10(5) infectious units of HR-1 virus likewise developed no recognizable clinical or haematological disease over several years of observation. Fourteen marmosets were inoculated with 10(2)-10(4) transforming units (TFU) of EBV strain B95-8; five of 11 animals inoculated with 10(3)-10(4) TFU of virus developed malignant lymphoma and died 31-110 days PI. Antibodies to one or more EBV-specified antigens were detected in sera from nine of the inoculated marmosets. EBV-carrying lymphoblastoid cell cultures were established from the spleen and lymph-nodes of one animal that died with malignant lymphoma and from another animal that died 19 days PI from undetermined causes.", "contents": "Response of marmosets to experimental infection with Epstein-Barr virus. The response of cotton-topped (CT) or white-lipped (WL) marmosets, inoculated with material containing Epstein-Barr virus (EBV), was studied. Twenty-five marmosets inoculated with 10(6)-10(8) cells from human or simian EBV-carrying lymphoblastoid cell cultures developed no detectable clinical disease. Transitory antibody titres to VCA were detected in sera from several of these marmosets. Thirty-eight marmosets inoculated with P3 virus (10(9) particles) and seven marmosets inoculated with 10(5) infectious units of HR-1 virus likewise developed no recognizable clinical or haematological disease over several years of observation. Fourteen marmosets were inoculated with 10(2)-10(4) transforming units (TFU) of EBV strain B95-8; five of 11 animals inoculated with 10(3)-10(4) TFU of virus developed malignant lymphoma and died 31-110 days PI. Antibodies to one or more EBV-specified antigens were detected in sera from nine of the inoculated marmosets. EBV-carrying lymphoblastoid cell cultures were established from the spleen and lymph-nodes of one animal that died with malignant lymphoma and from another animal that died 19 days PI from undetermined causes."}
{"id": "PMID:191366", "title": "Humoral and cellular immunity to EBV and lymphoid cell line antigens in human lymphoma.", "content": "Although elevated antibody levels to the Epstein-Barr virus (EBV) have been reported in a number of lympho-proliferative neoplasms, it has not been possible to determine whether these antibodies were the result of a specific response to an oncogenic agent (EBV), whether they were a non-specific humoral compensation for depressed cell-mediated immunity (CMI), or whether a different mechanism was responsible. We have previously shown in a group of lymphoma patients that depressed cellular immunity to a number of standard antigens (Candida, SKSD, etc.) is not associated with an increase in antibody to EBV. In this study, we tried to compare CMI to possible EBV and lymphoid cell line antigens with humoral antibody to EBV. The two basis CMI assays utilized were lymphocyte cytotoxicity (LC) and skin testing (ST) for delayed hypersensitivity. In the LC assay, an EBV-containing cell line (F265) was used as the target. Reactivity against F265 was stronger in normal individuals than in cancer patients, suggesting a relationship to general cellular immune competence. ST studies showed that membrane extracts from lymphoid cell lines derived from patients with Burkitt's lymphoma and nasopharyngeal carcinoma (NPC) were more likely to elicit a delayed hypersensitivity in lymphoma and NPC patients than cell lines derived from normal individuals. Patients with ST reactivity against the membrane preparations from the tumour-derived cell lines were as likely to have elevated EBV antibodies as patients without such reactivity. The data strongly indicated that the elevated EBV titres in lymphoma patients are not related to a specific or non-specific depression of CMI.", "contents": "Humoral and cellular immunity to EBV and lymphoid cell line antigens in human lymphoma. Although elevated antibody levels to the Epstein-Barr virus (EBV) have been reported in a number of lympho-proliferative neoplasms, it has not been possible to determine whether these antibodies were the result of a specific response to an oncogenic agent (EBV), whether they were a non-specific humoral compensation for depressed cell-mediated immunity (CMI), or whether a different mechanism was responsible. We have previously shown in a group of lymphoma patients that depressed cellular immunity to a number of standard antigens (Candida, SKSD, etc.) is not associated with an increase in antibody to EBV. In this study, we tried to compare CMI to possible EBV and lymphoid cell line antigens with humoral antibody to EBV. The two basis CMI assays utilized were lymphocyte cytotoxicity (LC) and skin testing (ST) for delayed hypersensitivity. In the LC assay, an EBV-containing cell line (F265) was used as the target. Reactivity against F265 was stronger in normal individuals than in cancer patients, suggesting a relationship to general cellular immune competence. ST studies showed that membrane extracts from lymphoid cell lines derived from patients with Burkitt's lymphoma and nasopharyngeal carcinoma (NPC) were more likely to elicit a delayed hypersensitivity in lymphoma and NPC patients than cell lines derived from normal individuals. Patients with ST reactivity against the membrane preparations from the tumour-derived cell lines were as likely to have elevated EBV antibodies as patients without such reactivity. The data strongly indicated that the elevated EBV titres in lymphoma patients are not related to a specific or non-specific depression of CMI."}
{"id": "PMID:191367", "title": "Epstein-Barr virus (EBV)-associated antibody patterns in relation to the deficiency of cell-mediated immunity in patients with Hodgkin's disease.", "content": "Sera from unselected and untreated patients with Hodgkin's disease (HD) were examined for antibodies to Epstein-Barr viral (EBV) capsid antigens (VCA). Delayed cutaneous hypersensitivity reactions were carried out with purified tuberculoprotein (PPD). Highly purified blood lymphocytes of the same patients were studied morphologically and classified for cell surface markers. Incorporation of 14C-thymidine was used as a measure of spontaneous DNA synthesis and DNA synthesis after exposure to different concentrations of three mitogens (PHA, Conconavalin A and pokeweed mitogen) and PPD. The distribution of EBV titres was in good agreement with previous reports. Most patients were lymphopenic, due to subnormal levels of T lymphocytes. The lymphocyte stimulation and skin tests showed different degrees of impairment in a considerable number of the patients. The results in 43 patients indicated that a relation exists between the immune defect and the anti-VCA titres. High serological anti-VCA reactivity was related to a poor cutaneous response to PPD, a decreased level of T lymphocytes in the blood and a depression of mitogen-induced DNA synthesis.", "contents": "Epstein-Barr virus (EBV)-associated antibody patterns in relation to the deficiency of cell-mediated immunity in patients with Hodgkin's disease. Sera from unselected and untreated patients with Hodgkin's disease (HD) were examined for antibodies to Epstein-Barr viral (EBV) capsid antigens (VCA). Delayed cutaneous hypersensitivity reactions were carried out with purified tuberculoprotein (PPD). Highly purified blood lymphocytes of the same patients were studied morphologically and classified for cell surface markers. Incorporation of 14C-thymidine was used as a measure of spontaneous DNA synthesis and DNA synthesis after exposure to different concentrations of three mitogens (PHA, Conconavalin A and pokeweed mitogen) and PPD. The distribution of EBV titres was in good agreement with previous reports. Most patients were lymphopenic, due to subnormal levels of T lymphocytes. The lymphocyte stimulation and skin tests showed different degrees of impairment in a considerable number of the patients. The results in 43 patients indicated that a relation exists between the immune defect and the anti-VCA titres. High serological anti-VCA reactivity was related to a poor cutaneous response to PPD, a decreased level of T lymphocytes in the blood and a depression of mitogen-induced DNA synthesis."}
{"id": "PMID:191368", "title": "Immunogenetic aspects of nasopharyngeal carcinoma (NPC) III. HL-a type as a genetic marker of NPC predisposition to test the hypothesis that Epstein-Barr virus is an etiological factor in NPC.", "content": "HL-A typing of 144 NPC patients and 236 controls revealed an increased frequency of 1st locus HL-42 (relative risk = 2.24) and an increased frequency of unidentified antigens at the 2nd locus (relative risk = 2.60) in the NPC patients. HL-A2 and the 2nd locus \"blank\" appeared to act together (HL-A2 blank haplotype) in determining NPC risk in highest-risk Cantonese, whereas in relatively lower-risk non-Cantonese Chinese (Hokkiens, Teochews) they appeared to act independently. Only the \"blank\" had an increased frequency in Malay NPC patients. Thus there was an indication that the strength of the HL-A association with NPC reflected the 30-50-fold difference in incidence between highest-risk Cantonese and lowest-risk Indians. In Singapore, HL-A segregation patterns in families of nine Chinese NPC patients confirmed that the \"blank\" was a genetic phenomenon. A new 2nd locus antigen (Singapore-2) has recently been detected. Singapore-2 occurs more frequently in NPC patients and appears to be associated with a high risk for NPC. Since HL-A2 and Singapore-2 are not the risk factors, it is likely that the HL-A association with NPC reflects the existence of disease-susceptibility (DS) genes in linkage disequilibrium with alleles of the HL-A loci. It is proposed that NPC-DS genes may determine differences in immune responsiveness to environmental agents, and thereby determine differences in NPC incidence. If the known altered immune responsiveness of NPC patients to EBV reflects the function of DS genes linked to the high NPC risk HL-A type, then the hypothesis that Epstein-Barr virus has an etiological role in NPC can be tested by several types of prospective studies.", "contents": "Immunogenetic aspects of nasopharyngeal carcinoma (NPC) III. HL-a type as a genetic marker of NPC predisposition to test the hypothesis that Epstein-Barr virus is an etiological factor in NPC. HL-A typing of 144 NPC patients and 236 controls revealed an increased frequency of 1st locus HL-42 (relative risk = 2.24) and an increased frequency of unidentified antigens at the 2nd locus (relative risk = 2.60) in the NPC patients. HL-A2 and the 2nd locus \"blank\" appeared to act together (HL-A2 blank haplotype) in determining NPC risk in highest-risk Cantonese, whereas in relatively lower-risk non-Cantonese Chinese (Hokkiens, Teochews) they appeared to act independently. Only the \"blank\" had an increased frequency in Malay NPC patients. Thus there was an indication that the strength of the HL-A association with NPC reflected the 30-50-fold difference in incidence between highest-risk Cantonese and lowest-risk Indians. In Singapore, HL-A segregation patterns in families of nine Chinese NPC patients confirmed that the \"blank\" was a genetic phenomenon. A new 2nd locus antigen (Singapore-2) has recently been detected. Singapore-2 occurs more frequently in NPC patients and appears to be associated with a high risk for NPC. Since HL-A2 and Singapore-2 are not the risk factors, it is likely that the HL-A association with NPC reflects the existence of disease-susceptibility (DS) genes in linkage disequilibrium with alleles of the HL-A loci. It is proposed that NPC-DS genes may determine differences in immune responsiveness to environmental agents, and thereby determine differences in NPC incidence. If the known altered immune responsiveness of NPC patients to EBV reflects the function of DS genes linked to the high NPC risk HL-A type, then the hypothesis that Epstein-Barr virus has an etiological role in NPC can be tested by several types of prospective studies."}
{"id": "PMID:191370", "title": "Alteration in Epstein-Barr virus-human lymphoid cell interactions caused by the presence of type-C viral genome.", "content": "We have recently established a cell line, designated FVNC, by infection of non-EBV-productive human lymphoid NC-37 cells with the type-C virus FLV. The FVNC cell line has been maintained free of detectable EBV- and FLV-related immunofluorescent antigens for three years but both viral genomes exist in the cells in a repressed form. The FVNC cells were morphologically similar to the uninfected NC-37 cells but a D-group chromosome change was consistently seen. The colony-forming capacity of FVNC cells in semi-solid agar medium was about 1/10 of that of NC-37, although the former grew rather faster than the latter in fluid culture. FVNC cells were three times more sensitive to EBV superinfection than NC-37, as shown by immunofluorescence. In addition, an obvious induction of FLV antigenic markers occurred in FVNC cells on exposure to EBV. Nucleic acid hybridization experiments showed a striking decrease in the number of EBV genomes in FVNC cells. The number of genomes was too small to be measured, but EBNA was clearly present in all FVNC cells as well as in NC-37 cells. The implications of these findings were discussed from the point of view of a possible co-carcinogenesis in man by EBV and the type-C virus.", "contents": "Alteration in Epstein-Barr virus-human lymphoid cell interactions caused by the presence of type-C viral genome. We have recently established a cell line, designated FVNC, by infection of non-EBV-productive human lymphoid NC-37 cells with the type-C virus FLV. The FVNC cell line has been maintained free of detectable EBV- and FLV-related immunofluorescent antigens for three years but both viral genomes exist in the cells in a repressed form. The FVNC cells were morphologically similar to the uninfected NC-37 cells but a D-group chromosome change was consistently seen. The colony-forming capacity of FVNC cells in semi-solid agar medium was about 1/10 of that of NC-37, although the former grew rather faster than the latter in fluid culture. FVNC cells were three times more sensitive to EBV superinfection than NC-37, as shown by immunofluorescence. In addition, an obvious induction of FLV antigenic markers occurred in FVNC cells on exposure to EBV. Nucleic acid hybridization experiments showed a striking decrease in the number of EBV genomes in FVNC cells. The number of genomes was too small to be measured, but EBNA was clearly present in all FVNC cells as well as in NC-37 cells. The implications of these findings were discussed from the point of view of a possible co-carcinogenesis in man by EBV and the type-C virus."}
{"id": "PMID:191373", "title": "Analysis and description of procedures used in the study of the relationship of herpes simplex virus \"non-virion\" antigens to certain cancers.", "content": "After a brief review of the relationship of herpes simplex viruses to certain human cancers, a description is given of procedures used in the study of herpesvirus \"non-virion\" antigens, and various points on which disagreement currently exists are discussed. Complement-fixation tests on these markers with both cancer and control sera as well as with \"non-virion\" antisera, which did not react with non-anti-complementary stored virion antigens, are described, and it is suggested that another parameter is now available for studies of squamous-cell carcinomas. The finding in certain tumours that expression of a repressed viral genome takes place proves that there is a continuing release of virus-specific messages and would indicate an important role for the virus in the development of the tumour.", "contents": "Analysis and description of procedures used in the study of the relationship of herpes simplex virus \"non-virion\" antigens to certain cancers. After a brief review of the relationship of herpes simplex viruses to certain human cancers, a description is given of procedures used in the study of herpesvirus \"non-virion\" antigens, and various points on which disagreement currently exists are discussed. Complement-fixation tests on these markers with both cancer and control sera as well as with \"non-virion\" antisera, which did not react with non-anti-complementary stored virion antigens, are described, and it is suggested that another parameter is now available for studies of squamous-cell carcinomas. The finding in certain tumours that expression of a repressed viral genome takes place proves that there is a continuing release of virus-specific messages and would indicate an important role for the virus in the development of the tumour."}
{"id": "PMID:191375", "title": "Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study - a review.", "content": "Samples of Chinese, Indian, African and Caucasian populations, randomly selected in Hong Kong, Singapore, the West Nile District of Uganda, and Nancy, France, were titrated for antibodies to EBV, viral capsid (VCA) and complement-fixing soluble (CF/S) antigens. The age-specific prevalence of infection (as reflected by the proportion of VCA-positive individuals) varied greatly up to the age of 10 years in the four populations studied, the West Nile District of Uganda being outstanding in having an early and massive infection rate. Differences were also observed between ethnic groups in Singapore, where the Chinese appeared to have a delayed infection rate compared to the Indians. Immune response, as measured by the prevalence of CF/S antibodies and by the geometric mean titres (GMT) of VCA and CF/S antibodies, differed significantly between ethnic groups, Ugandan infants (1-3-year age-groups) having a humoral response to VCA and CF/S antigens as high as or higher than that of Burkitt's lymphoma patients, decreasing thereafter to levels lower than those of any other ethnic group observed. Indians in Singapore, known to be at no risk for NPC and BL, exhibited a higher and steadier immune response to VCA in going from young to old age-groups than did the Chinese.", "contents": "Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study - a review. Samples of Chinese, Indian, African and Caucasian populations, randomly selected in Hong Kong, Singapore, the West Nile District of Uganda, and Nancy, France, were titrated for antibodies to EBV, viral capsid (VCA) and complement-fixing soluble (CF/S) antigens. The age-specific prevalence of infection (as reflected by the proportion of VCA-positive individuals) varied greatly up to the age of 10 years in the four populations studied, the West Nile District of Uganda being outstanding in having an early and massive infection rate. Differences were also observed between ethnic groups in Singapore, where the Chinese appeared to have a delayed infection rate compared to the Indians. Immune response, as measured by the prevalence of CF/S antibodies and by the geometric mean titres (GMT) of VCA and CF/S antibodies, differed significantly between ethnic groups, Ugandan infants (1-3-year age-groups) having a humoral response to VCA and CF/S antigens as high as or higher than that of Burkitt's lymphoma patients, decreasing thereafter to levels lower than those of any other ethnic group observed. Indians in Singapore, known to be at no risk for NPC and BL, exhibited a higher and steadier immune response to VCA in going from young to old age-groups than did the Chinese."}
{"id": "PMID:191376", "title": "Studies of the nature of herpesvirus-induced tumour-associated antigens induced by herpes simplex virus type 1 and further analysis of their relationship with squamous-cell carcinomas of the head and neck region.", "content": "The differences seen in levels of antibody response to HSV-TAA between non-laryngeal and laryngeal cancers in cured and untreated patient populations were due to the use of filtered sera. In previous and present studies using unfiltered sera, these differences were not noted. Of unfiltered sera from patients with squamous-cell carcinomas of the head and neck, 89% (49 out of 55) were positive for CF reactivity to HSV-TAA, and 44% of these unfiltered sera had titres of 1:4 or greater to 44 microng of antigen. The upper band of the antigen appears to be present in early provirus formation and is highly unstable whereas the lower band does not seem to be part of the assembly process.", "contents": "Studies of the nature of herpesvirus-induced tumour-associated antigens induced by herpes simplex virus type 1 and further analysis of their relationship with squamous-cell carcinomas of the head and neck region. The differences seen in levels of antibody response to HSV-TAA between non-laryngeal and laryngeal cancers in cured and untreated patient populations were due to the use of filtered sera. In previous and present studies using unfiltered sera, these differences were not noted. Of unfiltered sera from patients with squamous-cell carcinomas of the head and neck, 89% (49 out of 55) were positive for CF reactivity to HSV-TAA, and 44% of these unfiltered sera had titres of 1:4 or greater to 44 microng of antigen. The upper band of the antigen appears to be present in early provirus formation and is highly unstable whereas the lower band does not seem to be part of the assembly process."}
{"id": "PMID:191382", "title": "Antibodies to herpesviruses in patients with cervical cancer and controls.", "content": "The indirect immunofluorescent test was used to detect antibodies to herpesviruses types 1 and 2, cytomegalovirus and EBV in sera from patients with cervical carcinoma, condyloma acuminatum and controls from Cali, Colombia, and a control group from the USA. No significant differences were found in the prevalence of antibodies to viral capsid antigens of HSV-1 and CMV among the groups studied. However, titres for HSV-2 were higher in the three groups from Cali (cervical carcinoma, condyloma and controls) than in the control groups from USA. High EBV antibody titres (VCA and early antigens) were found in the three groups from Cali. Antibodies to early antigens of CMV were detected in a sub-sample of the subjects and with higher frequency in patients with cervical cancer. The significance of these findings is discussed.", "contents": "Antibodies to herpesviruses in patients with cervical cancer and controls. The indirect immunofluorescent test was used to detect antibodies to herpesviruses types 1 and 2, cytomegalovirus and EBV in sera from patients with cervical carcinoma, condyloma acuminatum and controls from Cali, Colombia, and a control group from the USA. No significant differences were found in the prevalence of antibodies to viral capsid antigens of HSV-1 and CMV among the groups studied. However, titres for HSV-2 were higher in the three groups from Cali (cervical carcinoma, condyloma and controls) than in the control groups from USA. High EBV antibody titres (VCA and early antigens) were found in the three groups from Cali. Antibodies to early antigens of CMV were detected in a sub-sample of the subjects and with higher frequency in patients with cervical cancer. The significance of these findings is discussed."}
{"id": "PMID:191389", "title": "Genetic analysis by chromosome-mediated gene transfer.", "content": "A general method is presented for stable transfer of genetic information to eukaryotic cells, utilizing metaphase chromosomes as the vehicle. Recent progress, current problems and large areas of uncertainty in this field are reviewed; particular consideration is given to frequency of transfer, size of the transgenome, evidence of cotransfer of linked genes and serial chromosome transfer. A reasonable model for chromosome transfer is considered with respect to the available information, and various descrepancies are noted. The utility of this method for fine structural mapping, cloning small regions of the eukaryotic genome and other potential applications are discussed.", "contents": "Genetic analysis by chromosome-mediated gene transfer. A general method is presented for stable transfer of genetic information to eukaryotic cells, utilizing metaphase chromosomes as the vehicle. Recent progress, current problems and large areas of uncertainty in this field are reviewed; particular consideration is given to frequency of transfer, size of the transgenome, evidence of cotransfer of linked genes and serial chromosome transfer. A reasonable model for chromosome transfer is considered with respect to the available information, and various descrepancies are noted. The utility of this method for fine structural mapping, cloning small regions of the eukaryotic genome and other potential applications are discussed."}
{"id": "PMID:191391", "title": "Effects of cholera exotoxin on Fc receptor activity of lymphoid cells and mononuclear phagocytes.", "content": "The effect of cholera exotoxin and aminophylline on Fc receptors in a murine lymphoid-cell line and in rabbit pulmonary alveolar macrophages has been investigated. Although both agents elevated intracellular cyclic AMP levels in macrophages and lymphoid cells, the effects on Fc receptor expression were distinct. Cholera toxin at 10 microng/ml reversibly inhibited Fc-receptor activity in the murine lymphoid cell line. In contrast, cholera toxin at 10 microng/ml or 0-01 microng/ml was ineffective in altering pulmonary alveolar macrophage receptor expression. Fc receptor activity on the macrophage was reduced by 20-30 per cent following incubation with aminophylline, (10(-3)M) from 0-6 h. There was no direct correlation between Fc-receptor activity and cyclic AMP levels in the cells studied. The differential susceptibility of these lymphoid and phagocytic cell populations to cholera toxin and also toward aminophylline suggests that there may be fundamental differences in topography on the membrane surface, or in the intracellular regulation of Fc receptors between lymphoid and phagocytic cells.", "contents": "Effects of cholera exotoxin on Fc receptor activity of lymphoid cells and mononuclear phagocytes. The effect of cholera exotoxin and aminophylline on Fc receptors in a murine lymphoid-cell line and in rabbit pulmonary alveolar macrophages has been investigated. Although both agents elevated intracellular cyclic AMP levels in macrophages and lymphoid cells, the effects on Fc receptor expression were distinct. Cholera toxin at 10 microng/ml reversibly inhibited Fc-receptor activity in the murine lymphoid cell line. In contrast, cholera toxin at 10 microng/ml or 0-01 microng/ml was ineffective in altering pulmonary alveolar macrophage receptor expression. Fc receptor activity on the macrophage was reduced by 20-30 per cent following incubation with aminophylline, (10(-3)M) from 0-6 h. There was no direct correlation between Fc-receptor activity and cyclic AMP levels in the cells studied. The differential susceptibility of these lymphoid and phagocytic cell populations to cholera toxin and also toward aminophylline suggests that there may be fundamental differences in topography on the membrane surface, or in the intracellular regulation of Fc receptors between lymphoid and phagocytic cells."}
{"id": "PMID:191397", "title": "In vivo interference in vesicular stomatitis virus infection.", "content": "Inactivated defective interfering and complete particles of vesicular stomatitis virus given intracerebrally to adult mice protect them against challenge with homologous virus whether this is given at the same time or several days later. Two separate protective processes appear to be involved. The first, which comes into operation immediately after inoculation, is also effective against heterologous strains of vesicular stomatitis virus, rabies (another rhabdovirus), and a neurotropic strain of foot-and-mouth disease virus. The second, later effect, which is strain specific, appears to be correlated with the appearance of circulating neutralizing antibody. Our results suggest that the protective effect that Holland and his colleagues described using defective interfering particles of vesicular stomatitis virus may also be accounted for by an immunological mechanism rather than one involving interference.", "contents": "In vivo interference in vesicular stomatitis virus infection. Inactivated defective interfering and complete particles of vesicular stomatitis virus given intracerebrally to adult mice protect them against challenge with homologous virus whether this is given at the same time or several days later. Two separate protective processes appear to be involved. The first, which comes into operation immediately after inoculation, is also effective against heterologous strains of vesicular stomatitis virus, rabies (another rhabdovirus), and a neurotropic strain of foot-and-mouth disease virus. The second, later effect, which is strain specific, appears to be correlated with the appearance of circulating neutralizing antibody. Our results suggest that the protective effect that Holland and his colleagues described using defective interfering particles of vesicular stomatitis virus may also be accounted for by an immunological mechanism rather than one involving interference."}
{"id": "PMID:191398", "title": "C-type virus protein p30 in blood from inbred mice correlates with their later incidence of leukemia.", "content": "The major core protein, p30, of mouse C-type viruses was quantitated radioimmunologically in lymphoid organs and blood from inbred strains of mice. The concentration of p30 in thymus and spleen had a weak and moderate correlation, respectively, to leukemia frequency. In contrast, the concentration of p30 in blood from mice with a high incidence of leukemia (strains AKR and C58) was 100-fold increased at 2 months of age compared with 10 strains with a low incidence of the disease. The SJL mice, which have a high incidence of reticulum cell neoplasms, showed generally elevated, but variable, values. The high concentration in AKR blood developed during the first weeks of life. Approximately one-third of the DBA/2 mice had elevated levels after 4 to 5 months, whereas the values from mice of the 129 strain were low irrespective in their age. The major part of p30 appeared to be associated with the erythrocytes. The concentration of p30 in the blood seems to reflect the presence of replicating virus in mice. It identifies among the inbred strains a high leukemia group one-half year prior to disease.", "contents": "C-type virus protein p30 in blood from inbred mice correlates with their later incidence of leukemia. The major core protein, p30, of mouse C-type viruses was quantitated radioimmunologically in lymphoid organs and blood from inbred strains of mice. The concentration of p30 in thymus and spleen had a weak and moderate correlation, respectively, to leukemia frequency. In contrast, the concentration of p30 in blood from mice with a high incidence of leukemia (strains AKR and C58) was 100-fold increased at 2 months of age compared with 10 strains with a low incidence of the disease. The SJL mice, which have a high incidence of reticulum cell neoplasms, showed generally elevated, but variable, values. The high concentration in AKR blood developed during the first weeks of life. Approximately one-third of the DBA/2 mice had elevated levels after 4 to 5 months, whereas the values from mice of the 129 strain were low irrespective in their age. The major part of p30 appeared to be associated with the erythrocytes. The concentration of p30 in the blood seems to reflect the presence of replicating virus in mice. It identifies among the inbred strains a high leukemia group one-half year prior to disease."}
{"id": "PMID:191399", "title": "Persistence of cytomegalovirus in human lymphoblasts and peripheral leukocyte cultures.", "content": "The in vitro susceptibility of human peripheral lymhpocytes and lymphoblastoid (F265) cells to infection by human cytomegalovirus was examined. Infection of these cell types with cytomegalovirus resulted in a persistent type of infection rather than the typical growth curve observed with permissive fibroblastic cells. When infection of peripheral lymphocytes was associated with a blastogenic response, the virus persisted for a longer time and at a higher titer than in cells in which a blastogenic response did not occur. Autoradiographic studies and infectious-center assays indicated that only a small number of cells, resembling lymphocytes, were involved in virus persistence. Whether or not the persistence of the virus indicates release of input virus or synthesis or new virus was not determined.", "contents": "Persistence of cytomegalovirus in human lymphoblasts and peripheral leukocyte cultures. The in vitro susceptibility of human peripheral lymhpocytes and lymphoblastoid (F265) cells to infection by human cytomegalovirus was examined. Infection of these cell types with cytomegalovirus resulted in a persistent type of infection rather than the typical growth curve observed with permissive fibroblastic cells. When infection of peripheral lymphocytes was associated with a blastogenic response, the virus persisted for a longer time and at a higher titer than in cells in which a blastogenic response did not occur. Autoradiographic studies and infectious-center assays indicated that only a small number of cells, resembling lymphocytes, were involved in virus persistence. Whether or not the persistence of the virus indicates release of input virus or synthesis or new virus was not determined."}
{"id": "PMID:191400", "title": "Oncogenicity of avian leukosis viruses of different subgroups and of mutants of sarcoma viruses.", "content": "Leukosis viruses of seven subgroups were tested for oncogenicity in chickens susceptible to virus infection and to development of lymphoid leukosis (LL) tumors. All subgroup A viruses and the subgroup B virus tested produced a high incidence of LL and other related neoplasms. Viruses of subgroup C and RAV-61 of subgroup F produced a low level of LL. The RAV-50 of subgroup D produced osteopetrosis. In these tests, the viruses of subgroup E and G and one virus of subgroup F were not pathogenic, possibly because infection was not established in the chickens, the chickens were not susceptible to tumor development by these viruses, or the viruses lacked oncogenicity. All temperature-sensitive mutants of Rous sarcoma virus produced sarcomas, but the level varied. One nontransforming mutant produced sarcomas, and the other three tested produced LL. All three mutants that cause cells to grow as colonies in agar produced a high incidence of sarcomas. Thus, sarcoma viruses, by back-mutation, may lose the ability to transform cells in vitro, to make cells grow in agar colonies, or to induce sarcomas in vivo, yet they retain the ability to produce LL. Conversely, it was previously shown that leukosis viruses may be changed into viruses that transform cells in vitro and produce sarcomas in vivo by suitable passage in chicks.", "contents": "Oncogenicity of avian leukosis viruses of different subgroups and of mutants of sarcoma viruses. Leukosis viruses of seven subgroups were tested for oncogenicity in chickens susceptible to virus infection and to development of lymphoid leukosis (LL) tumors. All subgroup A viruses and the subgroup B virus tested produced a high incidence of LL and other related neoplasms. Viruses of subgroup C and RAV-61 of subgroup F produced a low level of LL. The RAV-50 of subgroup D produced osteopetrosis. In these tests, the viruses of subgroup E and G and one virus of subgroup F were not pathogenic, possibly because infection was not established in the chickens, the chickens were not susceptible to tumor development by these viruses, or the viruses lacked oncogenicity. All temperature-sensitive mutants of Rous sarcoma virus produced sarcomas, but the level varied. One nontransforming mutant produced sarcomas, and the other three tested produced LL. All three mutants that cause cells to grow as colonies in agar produced a high incidence of sarcomas. Thus, sarcoma viruses, by back-mutation, may lose the ability to transform cells in vitro, to make cells grow in agar colonies, or to induce sarcomas in vivo, yet they retain the ability to produce LL. Conversely, it was previously shown that leukosis viruses may be changed into viruses that transform cells in vitro and produce sarcomas in vivo by suitable passage in chicks."}
{"id": "PMID:191401", "title": "Effect of rheumatoid factor and anti-immunoglobulin G antibodies on complement-mediated lysis of herpes simplex virus-infected human fibroblasts.", "content": "The effect of various anti-immunoglobulin G (IgG) antibodies on the complement-mediated lysis of herpes simplex virus-infected human fibroblasts was determined. IgM rheumatoid factor, a naturally occurring anti-human Fc, inhibited lysis, whereas rabbit anti-human IgG serum potentiated immune cytolysis. We attempted to explain this disparity by determining the effect various classess of anti-IgG's with differing specificities had on complement-mediated lysis. Inhibition of cytolysis occurred with IgM anti-Fc and all of the IgG antiglobulins (anti-IgG, Fab, and Fc). In contrast, IgM anti-Fab enhanced lysis. IgM anti-IgG suppressed immune cytolysis when high concentrations of antiviral serum were incubated with the virus-infected cell, but augmented lysis when low concentrations of anti-herpes simplex virus antibody were exposed to the fibroblasts. The experiments indicated that whether a particular antiglobulin potentiates or inhibits lysis depends on the concentration of antibody bound to the target cells as well as the class and specificity of the antiglobulin exposed to the antibody-coated cell.", "contents": "Effect of rheumatoid factor and anti-immunoglobulin G antibodies on complement-mediated lysis of herpes simplex virus-infected human fibroblasts. The effect of various anti-immunoglobulin G (IgG) antibodies on the complement-mediated lysis of herpes simplex virus-infected human fibroblasts was determined. IgM rheumatoid factor, a naturally occurring anti-human Fc, inhibited lysis, whereas rabbit anti-human IgG serum potentiated immune cytolysis. We attempted to explain this disparity by determining the effect various classess of anti-IgG's with differing specificities had on complement-mediated lysis. Inhibition of cytolysis occurred with IgM anti-Fc and all of the IgG antiglobulins (anti-IgG, Fab, and Fc). In contrast, IgM anti-Fab enhanced lysis. IgM anti-IgG suppressed immune cytolysis when high concentrations of antiviral serum were incubated with the virus-infected cell, but augmented lysis when low concentrations of anti-herpes simplex virus antibody were exposed to the fibroblasts. The experiments indicated that whether a particular antiglobulin potentiates or inhibits lysis depends on the concentration of antibody bound to the target cells as well as the class and specificity of the antiglobulin exposed to the antibody-coated cell."}
{"id": "PMID:191402", "title": "Detection of latent cytomegalovirus in murine salivary and prostate explant cultures and cells.", "content": "After infection of adult mice, cytomegalovirus was detectable in salivary gland suspensions by tissue culture inoculation for up to 3 months. After these cultures had become negative, virus apparently latent in these tissues could be detected in explants of salivary and prostate glands and in cell lines derived from these explants. In some cases cycles of virus-induced cell injury and regrowth were observed. Murine cytomegalovirus plaque efficiency and morphology were evaluated in prostate and salivary gland cell cultures derived from previously infected and uninfected mice. No evidence of interference was detected, although plaques size was altered (larger) in prostate cells from previously infected mice. These studies indicate the presence of a range of suppression, latency, or effects of murine cytomegalovirus detectable after the resolution of active infection and provide methods for additional study of the establishment and activation of virus latency.", "contents": "Detection of latent cytomegalovirus in murine salivary and prostate explant cultures and cells. After infection of adult mice, cytomegalovirus was detectable in salivary gland suspensions by tissue culture inoculation for up to 3 months. After these cultures had become negative, virus apparently latent in these tissues could be detected in explants of salivary and prostate glands and in cell lines derived from these explants. In some cases cycles of virus-induced cell injury and regrowth were observed. Murine cytomegalovirus plaque efficiency and morphology were evaluated in prostate and salivary gland cell cultures derived from previously infected and uninfected mice. No evidence of interference was detected, although plaques size was altered (larger) in prostate cells from previously infected mice. These studies indicate the presence of a range of suppression, latency, or effects of murine cytomegalovirus detectable after the resolution of active infection and provide methods for additional study of the establishment and activation of virus latency."}
{"id": "PMID:191403", "title": "Interactions between calf alveolar macrophages and parainfluenza-3 virus.", "content": "Cells washed from the lungs of freshly killed calves (lung wash cells; LWC) were cytotoxic for calf kidney (CK) target cells infected with parainfluenzavirus type 3 (Pi-3) when assayed by chromium release. LWC collected from 25 calves, including two gnotobiotic animals that had not previously been infected with Pi-3, were all cytotoxic, giving a specific chromium release between 11 and 50%. Cytotoxicity was detected at ratios of LWC to target cell as low as 5:1. The cytotoxic reaction required viable LWC, was inhibited by Pi-3 antiserum, and was not the result of virus-induced damage to the target cells. The cytotoxic cells in the LWC population were identified as alveolar macrophages from observations on glass adherence, phagocytic activity, killing by silica and fine-structural appearance. When LWC were added to CK cells or organ cultures of bovine trachea infected with Pi-3, the yield of virus was reduced for the first 2 to 3 days. However, subsequently, Pi-3 virus replicated in the LWC. Infection of LWC with Pi-3 virus reduced their cytotoxic activity. The significance of these interactions between alveolar macrophages and Pi-3 virus is discussed.", "contents": "Interactions between calf alveolar macrophages and parainfluenza-3 virus. Cells washed from the lungs of freshly killed calves (lung wash cells; LWC) were cytotoxic for calf kidney (CK) target cells infected with parainfluenzavirus type 3 (Pi-3) when assayed by chromium release. LWC collected from 25 calves, including two gnotobiotic animals that had not previously been infected with Pi-3, were all cytotoxic, giving a specific chromium release between 11 and 50%. Cytotoxicity was detected at ratios of LWC to target cell as low as 5:1. The cytotoxic reaction required viable LWC, was inhibited by Pi-3 antiserum, and was not the result of virus-induced damage to the target cells. The cytotoxic cells in the LWC population were identified as alveolar macrophages from observations on glass adherence, phagocytic activity, killing by silica and fine-structural appearance. When LWC were added to CK cells or organ cultures of bovine trachea infected with Pi-3, the yield of virus was reduced for the first 2 to 3 days. However, subsequently, Pi-3 virus replicated in the LWC. Infection of LWC with Pi-3 virus reduced their cytotoxic activity. The significance of these interactions between alveolar macrophages and Pi-3 virus is discussed."}
{"id": "PMID:191404", "title": "JC virus, a human polyomavirus associated with progressive multifocal leukoencephalopathy: additional biological characteristics and antigenic relationships.", "content": "JC virus, a human polyomavirus, failed to grow or produce cytopathic effects in any of a variety of cells tested other than primary human fetal glial (PHFG) cells. Cells tested included other primary human cells and glial cells from other animals. Only a rare cell in inoculated insusceptible human cell cultures produced T or virion antigen. In PHFG cell cultures JC virus produced subtle cytopathic effects, and the majority of progeny remained cell associated. Only a few cells in the heterogenous PHFG cell cultures contained T antigen at 24 h postinoculation, and virion antigen was not detected until 48 h postinoculation. The infectivity of JC virus was resistant to inactivation by ether and by heating at 50 degrees C for 1 h. A three-way minor antigenic relationship was demonstrated among the virion antigens of JC virus, BK virus, and simian virus 40 by neurtralization and/or hemagglutination inhibition tests. Serological evidence is presented for the existence of JC virus as a distinct entity before the use of simian virus 40-contaminated poliovirus vaccines and for the nonexistence of an animal reservoir for JC virus infection.", "contents": "JC virus, a human polyomavirus associated with progressive multifocal leukoencephalopathy: additional biological characteristics and antigenic relationships. JC virus, a human polyomavirus, failed to grow or produce cytopathic effects in any of a variety of cells tested other than primary human fetal glial (PHFG) cells. Cells tested included other primary human cells and glial cells from other animals. Only a rare cell in inoculated insusceptible human cell cultures produced T or virion antigen. In PHFG cell cultures JC virus produced subtle cytopathic effects, and the majority of progeny remained cell associated. Only a few cells in the heterogenous PHFG cell cultures contained T antigen at 24 h postinoculation, and virion antigen was not detected until 48 h postinoculation. The infectivity of JC virus was resistant to inactivation by ether and by heating at 50 degrees C for 1 h. A three-way minor antigenic relationship was demonstrated among the virion antigens of JC virus, BK virus, and simian virus 40 by neurtralization and/or hemagglutination inhibition tests. Serological evidence is presented for the existence of JC virus as a distinct entity before the use of simian virus 40-contaminated poliovirus vaccines and for the nonexistence of an animal reservoir for JC virus infection."}
{"id": "PMID:191405", "title": "Adjuvant effect of amorphous silica on the immune response to various antigens in guinea pigs.", "content": "The adjuvant effect of a subcutaneously injected amorphous silica (Aerosil) to various antigens was studied in guinea pigs. It was demonstrated that silica is able to enhance the humoral immune response to particulate and soluble antigens widely differing in molecular weight and that, in the system employed, adsorption of antigen on silica particles is not absolutely required for its adjuvanticity.", "contents": "Adjuvant effect of amorphous silica on the immune response to various antigens in guinea pigs. The adjuvant effect of a subcutaneously injected amorphous silica (Aerosil) to various antigens was studied in guinea pigs. It was demonstrated that silica is able to enhance the humoral immune response to particulate and soluble antigens widely differing in molecular weight and that, in the system employed, adsorption of antigen on silica particles is not absolutely required for its adjuvanticity."}
{"id": "PMID:191406", "title": "Heterogeneity of Epstein-Barr virus originating from P3HR-1 cells. I. Studies on EBNA induction.", "content": "Infection of EBV-negative human B-lymphoma cells of the lines BJAB and Ramos with EBV from P3HR-1 or B95-8 cells resulted in gradual conversion of these cells to EBNA synthesis. Whereas B 95-8 virus-infected cells exhibited a uniform brilliant EBNA fluorescence, two distinct fluorescence patterns were observed in P3HR-1 virus-converted BJAB and Ramos cells, a faint granular and a brilliant fluorescence, with predominance of the faint granular pattern. Cloning of P3HR-1 virus-converted BJAB cells resulted in 20 clones, 11 of them showing the heterogenous parental pattern, six revealing exclusively faint granular EBNA staining, and three with brilliantly stained nuclei, containing also a varying percentage of EBNA-negative cells. Further subcloning of one of the latter clones resulted in 26 subclones with brilliant EBNA expression, always segregating a significant percentage of EBNA-negative cells and one entirely EBNA-negative subclone. Reassociation kinetics did not reveal striking differences in the genome content of clones showing exclusively the faint granular or the brilliant type of EBNA expression. The EBNA-negative clone did not contain detectable amounts of EBV-DNA. Upon superinfection of the converted clones by the parental P3HR-1 virus, a significant increase in EA induction was noted when compared to non-converted BJAB and Ramos cells. This accounted in particular for cells with faint granular EBNA expression. These data support previous interpretations (Fresen and zur Hausen, 1976), suggesting the existence of at least two populations of EBV molecules within P3HR-1 cells. The reason for the apparently labile association of P3HR-1 EBV genomes inducing the brilliant EBNA flourescence in BJAB cells still remains obscure. The possible existence of a \"helper\" effect, exerted by the faint granular EBNA-inducing virus in stabilizing the persistence of the former, is discussed.", "contents": "Heterogeneity of Epstein-Barr virus originating from P3HR-1 cells. I. Studies on EBNA induction. Infection of EBV-negative human B-lymphoma cells of the lines BJAB and Ramos with EBV from P3HR-1 or B95-8 cells resulted in gradual conversion of these cells to EBNA synthesis. Whereas B 95-8 virus-infected cells exhibited a uniform brilliant EBNA fluorescence, two distinct fluorescence patterns were observed in P3HR-1 virus-converted BJAB and Ramos cells, a faint granular and a brilliant fluorescence, with predominance of the faint granular pattern. Cloning of P3HR-1 virus-converted BJAB cells resulted in 20 clones, 11 of them showing the heterogenous parental pattern, six revealing exclusively faint granular EBNA staining, and three with brilliantly stained nuclei, containing also a varying percentage of EBNA-negative cells. Further subcloning of one of the latter clones resulted in 26 subclones with brilliant EBNA expression, always segregating a significant percentage of EBNA-negative cells and one entirely EBNA-negative subclone. Reassociation kinetics did not reveal striking differences in the genome content of clones showing exclusively the faint granular or the brilliant type of EBNA expression. The EBNA-negative clone did not contain detectable amounts of EBV-DNA. Upon superinfection of the converted clones by the parental P3HR-1 virus, a significant increase in EA induction was noted when compared to non-converted BJAB and Ramos cells. This accounted in particular for cells with faint granular EBNA expression. These data support previous interpretations (Fresen and zur Hausen, 1976), suggesting the existence of at least two populations of EBV molecules within P3HR-1 cells. The reason for the apparently labile association of P3HR-1 EBV genomes inducing the brilliant EBNA flourescence in BJAB cells still remains obscure. The possible existence of a \"helper\" effect, exerted by the faint granular EBNA-inducing virus in stabilizing the persistence of the former, is discussed."}
{"id": "PMID:191407", "title": "Tumour-specific antibodies reactive with cell-surface antigens in children with Wilms' tumour.", "content": "Tumour-specific antibodies directed against membrane antigens were demonstrated by immunofluorescence in three of 45 patients with Wilms' tomour. Antibody capable of collaborating with K cells to kill Wilms' tumour was present in two additional patients. No patient exhibited both membrane immunofluorescence and K-cell collaborating antibody. Of 27 patients with non-renal solid tumours and 52 age-matched controls, none possessed tumour-specific antibody.", "contents": "Tumour-specific antibodies reactive with cell-surface antigens in children with Wilms' tumour. Tumour-specific antibodies directed against membrane antigens were demonstrated by immunofluorescence in three of 45 patients with Wilms' tomour. Antibody capable of collaborating with K cells to kill Wilms' tumour was present in two additional patients. No patient exhibited both membrane immunofluorescence and K-cell collaborating antibody. Of 27 patients with non-renal solid tumours and 52 age-matched controls, none possessed tumour-specific antibody."}
{"id": "PMID:191408", "title": "Lymphocyte responses to EBV-associated antigens in infectious mononucleosis, and Hodgkin's and non-Hodgkin's lymphoma patients, with the leukocyte adherence inhibition assay.", "content": "The leukocyte adherence inhibition (LAI) assay was utilized as a test for cellular immunity to Epstein-Barr virus (EBV) antigens in 22 patients with infectious mononucleosis (IM), 47 patients with lymphoma, 101 carcinoma patients, and 84 subjects without cancer. Response to EB virion (\"v\") antigen was generally present at the time of diagnosis in the IM patients but the response to EB soluble (\"S\") antigen was delayed. An increased CMI response to \"v\" antigen was found in patients with IM, Hodgkin's disease and non-Hodgkin's lymphoma as compared to controls with and without cancer. Patients with Hodgkin's disease had depressed responses to the EBV-associated \"S\" antigen. The finding of increased LAI responses to \"v\" antigen in Hodgkin's disease patients with high EBV antibody titers conflicts with previous reports attributing high antibody responses against EBV to a generalized depressed cell-mediated immunity.", "contents": "Lymphocyte responses to EBV-associated antigens in infectious mononucleosis, and Hodgkin's and non-Hodgkin's lymphoma patients, with the leukocyte adherence inhibition assay. The leukocyte adherence inhibition (LAI) assay was utilized as a test for cellular immunity to Epstein-Barr virus (EBV) antigens in 22 patients with infectious mononucleosis (IM), 47 patients with lymphoma, 101 carcinoma patients, and 84 subjects without cancer. Response to EB virion (\"v\") antigen was generally present at the time of diagnosis in the IM patients but the response to EB soluble (\"S\") antigen was delayed. An increased CMI response to \"v\" antigen was found in patients with IM, Hodgkin's disease and non-Hodgkin's lymphoma as compared to controls with and without cancer. Patients with Hodgkin's disease had depressed responses to the EBV-associated \"S\" antigen. The finding of increased LAI responses to \"v\" antigen in Hodgkin's disease patients with high EBV antibody titers conflicts with previous reports attributing high antibody responses against EBV to a generalized depressed cell-mediated immunity."}
{"id": "PMID:191409", "title": "Genetic transmission of mammary tumour virus by GR mice.", "content": "By immunodiffusion assay (ID-test) milk samples of mice of several strains and of F1-hybrids of the GR strain were tested for the presence of mammary tumour virus (MTV) antigens. The results clearly demonstrated that the presence of viral antigens in the milk of the first lactation period is restricted to mice harbouring endogenous MTV-GR. Viral antigens were detectable in about 50% of the milk samples collected during the first (occasionally the second) lactation periods of mice of the segregating backcross I (Bc I) populations: DBAfX(DBAfXGR), AKRX(AKRXGR), BALB/cX(BALB/cXGR) and C57BLX(C57BLXGR), indicating that one dominant gene is responsible for the presence of viral antigens in the milk of GR mice. The proposed gene symbol is Mtv-2. Milk samples from female mice of three different Bc II populations were tested for the occurrence of viral antigens. In the first Bc II: [BALB/cX(BALB/cXGR)]XBALB/c 33 out of 51 mice, descending from ID-positive mothers, had ID-positive milk and only one out of 71 mice, which were the progeny of ID-NEGATIVE Bc I mothers, was ID-positive. These results may be influenced by the MTV transmitted extrachromosomally via the milk of the mother. The two other Bx II populations were derived from Bc I fathers, either [BALB/cX(BALB/cXGR)] or [(BALB/cXGR)XBALB/c] f and BALB/c females. The results obtained with these Bc II populations suggested that 6 Bc I fathers were heterozygous for Mtv-2. Since the segregation ratio (60:29) in the Bc II population (progeny of these 6 Bc I male) deviates significantly from the expected 1:1 ratio, one may assume extrachromosomal transmission of MTV via the seminal fluid of the father to the progeny. A close correlation was found between the presence of MTV antigens in the milk and the occurrence of both early mammary tumours after hormone treatment and spontaneous mammary tumours before the age of 13 months. These results suggest that the early appearance of mammary tumours in the GR strain and the early expression of MTV antigens in the milk appear to be controlled by the same genetic factors.", "contents": "Genetic transmission of mammary tumour virus by GR mice. By immunodiffusion assay (ID-test) milk samples of mice of several strains and of F1-hybrids of the GR strain were tested for the presence of mammary tumour virus (MTV) antigens. The results clearly demonstrated that the presence of viral antigens in the milk of the first lactation period is restricted to mice harbouring endogenous MTV-GR. Viral antigens were detectable in about 50% of the milk samples collected during the first (occasionally the second) lactation periods of mice of the segregating backcross I (Bc I) populations: DBAfX(DBAfXGR), AKRX(AKRXGR), BALB/cX(BALB/cXGR) and C57BLX(C57BLXGR), indicating that one dominant gene is responsible for the presence of viral antigens in the milk of GR mice. The proposed gene symbol is Mtv-2. Milk samples from female mice of three different Bc II populations were tested for the occurrence of viral antigens. In the first Bc II: [BALB/cX(BALB/cXGR)]XBALB/c 33 out of 51 mice, descending from ID-positive mothers, had ID-positive milk and only one out of 71 mice, which were the progeny of ID-NEGATIVE Bc I mothers, was ID-positive. These results may be influenced by the MTV transmitted extrachromosomally via the milk of the mother. The two other Bx II populations were derived from Bc I fathers, either [BALB/cX(BALB/cXGR)] or [(BALB/cXGR)XBALB/c] f and BALB/c females. The results obtained with these Bc II populations suggested that 6 Bc I fathers were heterozygous for Mtv-2. Since the segregation ratio (60:29) in the Bc II population (progeny of these 6 Bc I male) deviates significantly from the expected 1:1 ratio, one may assume extrachromosomal transmission of MTV via the seminal fluid of the father to the progeny. A close correlation was found between the presence of MTV antigens in the milk and the occurrence of both early mammary tumours after hormone treatment and spontaneous mammary tumours before the age of 13 months. These results suggest that the early appearance of mammary tumours in the GR strain and the early expression of MTV antigens in the milk appear to be controlled by the same genetic factors."}
{"id": "PMID:191410", "title": "Transformation of rabbit kidney cells by BKV(MM) human papovavirus.", "content": "Primary rabbit kidney cells were transformed by BKV(MM), a papovavirus isolated from the urine of a child with the Wiskott-Aldrich syndrome. The transformed cells contained BK T-antigen, but no antigen that reacted with SV40 U-antiserum. The transformed cells failed to produce tumors in nude mice, and BKV (MM) was not rescued from transformed cells by cell fusion or chemical induction methods. The transformed cells supported the growth of rabbit kidney vacuolating virus (RKV), and could be used to quantitate RKV by plaque formation under an agar overlay.", "contents": "Transformation of rabbit kidney cells by BKV(MM) human papovavirus. Primary rabbit kidney cells were transformed by BKV(MM), a papovavirus isolated from the urine of a child with the Wiskott-Aldrich syndrome. The transformed cells contained BK T-antigen, but no antigen that reacted with SV40 U-antiserum. The transformed cells failed to produce tumors in nude mice, and BKV (MM) was not rescued from transformed cells by cell fusion or chemical induction methods. The transformed cells supported the growth of rabbit kidney vacuolating virus (RKV), and could be used to quantitate RKV by plaque formation under an agar overlay."}
{"id": "PMID:191411", "title": "Isolation from a transmissible lymphoid tumour (TLT) lymphoblastoid cell line of a herpesvirus similar to Marek's disease virus.", "content": "A chicken lymphoblastoid cell line (TLT)-6855 originally established from an avian oncornavirus-induced lymphoma (Siegfried and Olson, 1972) was studied for the presence and expression of Marek's disease virus (MDV) genome. By nucleic acid hybridization a significant amount of MDV DNA was found in this cell line. This virus DNA, however, was not expressed in either virus-specific intracellular or membrane antigens or the MD-associated tumour-specific surface antigen (MATSA). Moreover, MDV-specific antigens could not be activated in this cell line by treatment with 5-IdUrd. In several experiments, when chickens were inoculated with the cell line a herpesvirus was repeatedly isolated from the kidneys. This herpesvirus was antigenically similar to MDV but was low in oncogenicity for chickens.", "contents": "Isolation from a transmissible lymphoid tumour (TLT) lymphoblastoid cell line of a herpesvirus similar to Marek's disease virus. A chicken lymphoblastoid cell line (TLT)-6855 originally established from an avian oncornavirus-induced lymphoma (Siegfried and Olson, 1972) was studied for the presence and expression of Marek's disease virus (MDV) genome. By nucleic acid hybridization a significant amount of MDV DNA was found in this cell line. This virus DNA, however, was not expressed in either virus-specific intracellular or membrane antigens or the MD-associated tumour-specific surface antigen (MATSA). Moreover, MDV-specific antigens could not be activated in this cell line by treatment with 5-IdUrd. In several experiments, when chickens were inoculated with the cell line a herpesvirus was repeatedly isolated from the kidneys. This herpesvirus was antigenically similar to MDV but was low in oncogenicity for chickens."}
{"id": "PMID:191412", "title": "Epstein-Barr virus antibodies in tonsillar carcinoma patients;.", "content": "Sera from 18 tonsillar carcinoma patients and from 18 matched control subjects were examined for the presence of antibodies to viral capsid antigen (VCA), early antigen (EA) and nuclear antigen (EBNA) of EB virus. Antibodies to all three antigens were found more frequently and in significantly higher titres in the tonsillar carcinoma patients than in control subjects.", "contents": "Epstein-Barr virus antibodies in tonsillar carcinoma patients;. Sera from 18 tonsillar carcinoma patients and from 18 matched control subjects were examined for the presence of antibodies to viral capsid antigen (VCA), early antigen (EA) and nuclear antigen (EBNA) of EB virus. Antibodies to all three antigens were found more frequently and in significantly higher titres in the tonsillar carcinoma patients than in control subjects."}
{"id": "PMID:191413", "title": "Column separation of viral capsid antigen (VCA)-positive cells from VCA-negative cells in an Epstein-Barr virus (EBV)-producing lymphoid line,.", "content": "Virus producing, VCA (viral capsid antigen)-positive cells could be selectively removed from Epstein-Barr virus (EBV)-carrying, virus-producer P3HR-1 cultures by two different methods of column passage. In the first, the virus-producing cells were covered with human EBV antibody and subsequently passaged through anti-human-Ig columns. In the second methods, untreated P3HR-1 cells were allowed to pass through columns of EBV receptor-positive cell lines or, as controls, EBV receptor-positive cell lines or, as controls, EBV receptor-negative cells. The majority of the VCA-positive cells were selectively removed by both techniques. The second method involves the attachment of EBV-producer cells, known to accumulate viral envelope material in their plasma membrane, to EBV receptors. In view of recent evidence indicating an association between EBV and complement receptors, human and mouse complement were tested for their ability to block this attachment. Fresh mouse and human complement regularly exerted blocking activity, whereas heat-inactivated human serum did not block. Heat-inactivated mouse serum did block occasionally, but the effect was more irregular than with fresh mouse serum. Trypsin treatment of the EBV-receptor colum abolished its ability to retain VCA-positive cells.", "contents": "Column separation of viral capsid antigen (VCA)-positive cells from VCA-negative cells in an Epstein-Barr virus (EBV)-producing lymphoid line,. Virus producing, VCA (viral capsid antigen)-positive cells could be selectively removed from Epstein-Barr virus (EBV)-carrying, virus-producer P3HR-1 cultures by two different methods of column passage. In the first, the virus-producing cells were covered with human EBV antibody and subsequently passaged through anti-human-Ig columns. In the second methods, untreated P3HR-1 cells were allowed to pass through columns of EBV receptor-positive cell lines or, as controls, EBV receptor-positive cell lines or, as controls, EBV receptor-negative cells. The majority of the VCA-positive cells were selectively removed by both techniques. The second method involves the attachment of EBV-producer cells, known to accumulate viral envelope material in their plasma membrane, to EBV receptors. In view of recent evidence indicating an association between EBV and complement receptors, human and mouse complement were tested for their ability to block this attachment. Fresh mouse and human complement regularly exerted blocking activity, whereas heat-inactivated human serum did not block. Heat-inactivated mouse serum did block occasionally, but the effect was more irregular than with fresh mouse serum. Trypsin treatment of the EBV-receptor colum abolished its ability to retain VCA-positive cells."}
{"id": "PMID:191414", "title": "The presence of Herpesvirus Saimiri genomes in virus-transformed cells.", "content": "Herpesvirus saimiri (H. salmiri) -transformed cells contained both types of viral DNA, unique L-DNA and highly repetetive H-DNA. DNA from spleen and lymph-node autopsies of two tumor-bearing marmoset monkeys contained 0.14-0.75% viral L-DNA -AND 0.115-1.08% H-DNA. This amount of H-DNA would be equivalent to the presence of 14-130 M-genomes per diploid tumor tissue cell. Six virus-transformed lymphoid cell lines, two of them virus-producing, contained 0.69-2.27% H-DNA and more than 0.72-1.95% L-DNA. These concentrations of H-DNA sequences correspond to 83-274 M-genome copies per lymphoid tissue culture cell. The majority of viral genomes in transformed non-producer lymphoid cell lines appeared to be defective, since part of the L-sequences present in virions were found to be deleted in the genome copies of transformed cells. There was a relative excess of repetitive H-sequences in all transformed cells in regard to the ratio of H-DNA/L-DNA in M-genomes of H. saimiri virions.", "contents": "The presence of Herpesvirus Saimiri genomes in virus-transformed cells. Herpesvirus saimiri (H. salmiri) -transformed cells contained both types of viral DNA, unique L-DNA and highly repetetive H-DNA. DNA from spleen and lymph-node autopsies of two tumor-bearing marmoset monkeys contained 0.14-0.75% viral L-DNA -AND 0.115-1.08% H-DNA. This amount of H-DNA would be equivalent to the presence of 14-130 M-genomes per diploid tumor tissue cell. Six virus-transformed lymphoid cell lines, two of them virus-producing, contained 0.69-2.27% H-DNA and more than 0.72-1.95% L-DNA. These concentrations of H-DNA sequences correspond to 83-274 M-genome copies per lymphoid tissue culture cell. The majority of viral genomes in transformed non-producer lymphoid cell lines appeared to be defective, since part of the L-sequences present in virions were found to be deleted in the genome copies of transformed cells. There was a relative excess of repetitive H-sequences in all transformed cells in regard to the ratio of H-DNA/L-DNA in M-genomes of H. saimiri virions."}
{"id": "PMID:191415", "title": "FeLV epidemiology in Los Angeles cats: Appraisal of detection methods.", "content": "We investigated the reliability of the fixed cell indirect fluorescent antibody (IFA) peripheral blood smear test as an index of systemic infection with FeLV. Positive results with this test were found to correlate well with detectable FeLV p30 antigen in bone-marrow smears by IFA, in serum and tissue by competition immunoassays, and with type-C particles in bone marrow or spleen by electron microscopy. Most cats with lymphoma, anemia or infectious peritonitis were positive for FeLV and showed a poor or absent antibody response to FeLV p30, gp70, and FOCMA antigens. Most older cats with lymphoma, carcinoma, or sarcoma were negative for FeLV expression and also lacked these FeLV-related antibodies. Detectable immunologic response to FeLV p30 and gp70 proteins and a high-titered FOCMA antibody response were generally restricted to certain healthy cats exposed to FeLV. Antibody to endogenous RD-114 viral p30 and gp70 was not detected in any of a large number of feline sera tested. The prevalence of FeLV-related diseases and immunologic responses to FeLV in healthy cats was directly correlated with the degree of FeLV exposure. By using the IFA blood smear and FOCMA antibody tests one can monitor the horizontal spread of FeLV in multi-cat household and accurately predict the FeLV disease susceptibilty or resistance of individual cats in each environments.", "contents": "FeLV epidemiology in Los Angeles cats: Appraisal of detection methods. We investigated the reliability of the fixed cell indirect fluorescent antibody (IFA) peripheral blood smear test as an index of systemic infection with FeLV. Positive results with this test were found to correlate well with detectable FeLV p30 antigen in bone-marrow smears by IFA, in serum and tissue by competition immunoassays, and with type-C particles in bone marrow or spleen by electron microscopy. Most cats with lymphoma, anemia or infectious peritonitis were positive for FeLV and showed a poor or absent antibody response to FeLV p30, gp70, and FOCMA antigens. Most older cats with lymphoma, carcinoma, or sarcoma were negative for FeLV expression and also lacked these FeLV-related antibodies. Detectable immunologic response to FeLV p30 and gp70 proteins and a high-titered FOCMA antibody response were generally restricted to certain healthy cats exposed to FeLV. Antibody to endogenous RD-114 viral p30 and gp70 was not detected in any of a large number of feline sera tested. The prevalence of FeLV-related diseases and immunologic responses to FeLV in healthy cats was directly correlated with the degree of FeLV exposure. By using the IFA blood smear and FOCMA antibody tests one can monitor the horizontal spread of FeLV in multi-cat household and accurately predict the FeLV disease susceptibilty or resistance of individual cats in each environments."}
{"id": "PMID:191417", "title": "Symmetrical features in polypeptide hormone-receptor interactions.", "content": "Symmetrical features were observed in the amino acid sequences of some biologically active peptides. It is suggested that this approximate symmetry is reflected in the conformations of the peptides at their respective biological receptors, and has arisen by natural selection as both peptides and receptors evolved to optimise their mutual fit. It follows that the binding site for each peptide at its receptor would share the same symmetry element. This would arise if the peptide binds to two symmetrically related similar or identical submits in the receptor.", "contents": "Symmetrical features in polypeptide hormone-receptor interactions. Symmetrical features were observed in the amino acid sequences of some biologically active peptides. It is suggested that this approximate symmetry is reflected in the conformations of the peptides at their respective biological receptors, and has arisen by natural selection as both peptides and receptors evolved to optimise their mutual fit. It follows that the binding site for each peptide at its receptor would share the same symmetry element. This would arise if the peptide binds to two symmetrically related similar or identical submits in the receptor."}
{"id": "PMID:191418", "title": "Synthesis and biological activities of two ACTH-analogues containing L-norarginine in position 8.", "content": "Two new ACTH-analogues, an octadecapeptide amide and a tetracosapeptide containing the lower homologue of arginine (norarginine) in position 8, have been synthesized by the generally accepted method. Special attention was paid to the synthesis of the required tetrapeptide representing the 7-10 sequence, which was obtained either by direct introduction of L-nitronorarginine or by amidination of the gamma-amino function in a protected peptide containing alpha, gamma-diaminobutyric acid. Biological activity determination showed that the shortening e arginine side chain in position 8 results in the formation of active ACTH-analogues.", "contents": "Synthesis and biological activities of two ACTH-analogues containing L-norarginine in position 8. Two new ACTH-analogues, an octadecapeptide amide and a tetracosapeptide containing the lower homologue of arginine (norarginine) in position 8, have been synthesized by the generally accepted method. Special attention was paid to the synthesis of the required tetrapeptide representing the 7-10 sequence, which was obtained either by direct introduction of L-nitronorarginine or by amidination of the gamma-amino function in a protected peptide containing alpha, gamma-diaminobutyric acid. Biological activity determination showed that the shortening e arginine side chain in position 8 results in the formation of active ACTH-analogues."}
{"id": "PMID:191419", "title": "Free radicals in pyrimidines:single crystals of dihydro-6-methyl uracil irradiated and observed at 77 K.", "content": "Electron-spin-resonance measurements have been made on single crystals of dihydro-6-methyl uracil, which were irradiated by 4-0 MeV electrons at 77 K. At low temperature, four radicals have been identified. Two, the C5 and C6 hydrogen abstraction radicals, were also studied in a previous work. On exposure of U.V., the C6 abstraction radical was found to convert into the C5 abstraction radical. Annealing at room temperature reversed the process. The other radicals identified are that formed after H-atom addition to O4, and that formed after H-atom abstractions from N1, C5, and C6. The latter was not present in deuterated crystals. Both radicals were found to be unstable at intermediate temperatures. Thermoluminescence glow-curves were found to correlate to the formation and the decay of these radicals. Semi-empirical INDO MO-calculations have been performed for identification purposes.", "contents": "Free radicals in pyrimidines:single crystals of dihydro-6-methyl uracil irradiated and observed at 77 K. Electron-spin-resonance measurements have been made on single crystals of dihydro-6-methyl uracil, which were irradiated by 4-0 MeV electrons at 77 K. At low temperature, four radicals have been identified. Two, the C5 and C6 hydrogen abstraction radicals, were also studied in a previous work. On exposure of U.V., the C6 abstraction radical was found to convert into the C5 abstraction radical. Annealing at room temperature reversed the process. The other radicals identified are that formed after H-atom addition to O4, and that formed after H-atom abstractions from N1, C5, and C6. The latter was not present in deuterated crystals. Both radicals were found to be unstable at intermediate temperatures. Thermoluminescence glow-curves were found to correlate to the formation and the decay of these radicals. Semi-empirical INDO MO-calculations have been performed for identification purposes."}
{"id": "PMID:191422", "title": "Cytologic diagnosis of adenoviral epidemic keratoconjunctivitis by direct immunofluorescence.", "content": "A direct immunofluorescence technique for the diagnosis of acute adenoviral keratoconjunctivitis and pharyngoconjunctivitis was found to be a reliable, sensitive, and specific technique for the detection of soluble adenoviral antigens in epithelial cells on conjunctival scrapings of patients with epidemic keratoconjunctivitis. Of 25 patients with clinical findings consistent with epidemic keratoconjunctivitis or pharyngoconjunctival fever, all had positive diagnostic scrapings by direct immunofluorescence.", "contents": "Cytologic diagnosis of adenoviral epidemic keratoconjunctivitis by direct immunofluorescence. A direct immunofluorescence technique for the diagnosis of acute adenoviral keratoconjunctivitis and pharyngoconjunctivitis was found to be a reliable, sensitive, and specific technique for the detection of soluble adenoviral antigens in epithelial cells on conjunctival scrapings of patients with epidemic keratoconjunctivitis. Of 25 patients with clinical findings consistent with epidemic keratoconjunctivitis or pharyngoconjunctival fever, all had positive diagnostic scrapings by direct immunofluorescence."}
{"id": "PMID:191423", "title": "Interaction of adrenergic agents with alpha-melanocyte-stimulating hormone and infrared irradiation of the iris in the rabbit eye.", "content": "Breakdown of the blood aqueous barrier in the rabbit eye induces a protein leakage into the aqueous humor, seen as a flare in the anterior chamber. A barrier damage was induced by topical prostaglandin E2(PGE2), infrared irradiation of the iris, or alpha-melanocyte-stimulating hormone (alpha-MSH) given subcutaneously. The aqueous flare was measured quantitatively by means of a photoelectric instrument. The interference of adrenergic antagonists and agonists on the breakdown of the barrier was tested. The alpha-adrenergic antagonist phentolamine and the beta-adrenergic antagonist propranolol, given intravenously, had no effect on exogenously administered PGE2, but both antagonists reduced the flare response to infrared irradiation which is supposed to exert its effect via endogenous prostaglandin release. The alpha-MSH response was unaffected by phentolamine, whereas propranolol abolished the flare response to alpha-MSH totally. The PGE1 response was unaffected both by the alpha-adrenergic agonist noradrenaline and the beta-adrenergic agonist terbutalin sulfate, administered topically. Noradrenaline, however, inhibited the flare response to infrared irradiation and facilitated the flare response to alpha-MSH. Terbutalin sulfate worked synergistically with both infrared irradiation and alpha-MSH. It is assumed that alpha-MSH exerts its effect on the barrier via enhanced beta-adrenergic activity, whereas the effects caused by infrared irradiation seem conditioned by intact alpha- as well as beta-adrnergic receptor sites.", "contents": "Interaction of adrenergic agents with alpha-melanocyte-stimulating hormone and infrared irradiation of the iris in the rabbit eye. Breakdown of the blood aqueous barrier in the rabbit eye induces a protein leakage into the aqueous humor, seen as a flare in the anterior chamber. A barrier damage was induced by topical prostaglandin E2(PGE2), infrared irradiation of the iris, or alpha-melanocyte-stimulating hormone (alpha-MSH) given subcutaneously. The aqueous flare was measured quantitatively by means of a photoelectric instrument. The interference of adrenergic antagonists and agonists on the breakdown of the barrier was tested. The alpha-adrenergic antagonist phentolamine and the beta-adrenergic antagonist propranolol, given intravenously, had no effect on exogenously administered PGE2, but both antagonists reduced the flare response to infrared irradiation which is supposed to exert its effect via endogenous prostaglandin release. The alpha-MSH response was unaffected by phentolamine, whereas propranolol abolished the flare response to alpha-MSH totally. The PGE1 response was unaffected both by the alpha-adrenergic agonist noradrenaline and the beta-adrenergic agonist terbutalin sulfate, administered topically. Noradrenaline, however, inhibited the flare response to infrared irradiation and facilitated the flare response to alpha-MSH. Terbutalin sulfate worked synergistically with both infrared irradiation and alpha-MSH. It is assumed that alpha-MSH exerts its effect on the barrier via enhanced beta-adrenergic activity, whereas the effects caused by infrared irradiation seem conditioned by intact alpha- as well as beta-adrnergic receptor sites."}
{"id": "PMID:191424", "title": "Retinal neoplasia and dysplasia. I. Induction by feline leukemia virus.", "content": "Feline leukemia virus, a naturally occurring C-type virus (oncorna virus), was injected systemically and intraocularly into fetal and newborn kittens. A light microscopy study of the resultant ocular tumor changes was carried out. One animal developed an intraocular tumor of apparent retinal origin. Eight animals showed intraocular neoplastic cell infiltration. The most common ocular change observed was retinal dysplasia. Sequential histologic examination of enucleated eyes showed diffuse intraocular inflammation after viral inoculation. In the developing retinas progressive disorganization and necrosis were documented, with subsequent reorganization into cell clumps and dysplastic rosette structures. The retinal pigment epithelium showed proliferation and intraretinal migration. The mature retina exhibited full-thickness folds and tubes associated with infoldings of the retinal pigment epithelium.", "contents": "Retinal neoplasia and dysplasia. I. Induction by feline leukemia virus. Feline leukemia virus, a naturally occurring C-type virus (oncorna virus), was injected systemically and intraocularly into fetal and newborn kittens. A light microscopy study of the resultant ocular tumor changes was carried out. One animal developed an intraocular tumor of apparent retinal origin. Eight animals showed intraocular neoplastic cell infiltration. The most common ocular change observed was retinal dysplasia. Sequential histologic examination of enucleated eyes showed diffuse intraocular inflammation after viral inoculation. In the developing retinas progressive disorganization and necrosis were documented, with subsequent reorganization into cell clumps and dysplastic rosette structures. The retinal pigment epithelium showed proliferation and intraretinal migration. The mature retina exhibited full-thickness folds and tubes associated with infoldings of the retinal pigment epithelium."}
{"id": "PMID:191426", "title": "The value of enzyme histochemical techniques in classifying fibre types of human skeletal muscle. 1. Adult skeletal muscles with no apparent disease of the neuromuscular system.", "content": "Fibre-type classification of human skeletal muscle into type I and type II fibres is mostly based on their slight or strong staining with the myosin adenosine triphosphatase reaction. In order to evaluate the reliability of this screening technique a combined histochemical and biochemical study was performed on normal and diseased skeletal muscle of human subjects. In the present investigation activities of enzymes which play a role in the aerobic and anaerobic pathways and which can characterize fibre type, were examined in muscle specimens, with no apparent disease of the neuromuscular system. Special attention is given to the maximal activities of phosphofructokinase and fructose-1,6-diphosphatase, the rate limiting enzymes for the regulation of the glycolysis and glyconeogenesis, respectively. A most important feature of the biochemical findings is the constancy of the activity ratios of the examined enzymes. From these results and from the histochemical results it can be concluded that in apparently normal adult human skeletal muscle the ATP-ase technique for type I and type II typing is reliable. For fibres with an intermediate intensity of staining with the myosin ATPase technique of typing it is also necessary to apply other enzyme histochemical techniques.", "contents": "The value of enzyme histochemical techniques in classifying fibre types of human skeletal muscle. 1. Adult skeletal muscles with no apparent disease of the neuromuscular system. Fibre-type classification of human skeletal muscle into type I and type II fibres is mostly based on their slight or strong staining with the myosin adenosine triphosphatase reaction. In order to evaluate the reliability of this screening technique a combined histochemical and biochemical study was performed on normal and diseased skeletal muscle of human subjects. In the present investigation activities of enzymes which play a role in the aerobic and anaerobic pathways and which can characterize fibre type, were examined in muscle specimens, with no apparent disease of the neuromuscular system. Special attention is given to the maximal activities of phosphofructokinase and fructose-1,6-diphosphatase, the rate limiting enzymes for the regulation of the glycolysis and glyconeogenesis, respectively. A most important feature of the biochemical findings is the constancy of the activity ratios of the examined enzymes. From these results and from the histochemical results it can be concluded that in apparently normal adult human skeletal muscle the ATP-ase technique for type I and type II typing is reliable. For fibres with an intermediate intensity of staining with the myosin ATPase technique of typing it is also necessary to apply other enzyme histochemical techniques."}
{"id": "PMID:191432", "title": "Composition and enzyme activities of Spiroplasma citri membranes.", "content": "Spiroplasma citri was cultured in three different media that supplied cholesterol and fatty acids from: (i) horse serum, (ii) pleuropneumonia-like organism (PPLO) serum fraction, or (iii) bovine serum albumin-fatty acid-cholesterol. The ability of PPLO serum fraction to support growth varied by lot number. Neither PPLO serum fraction nor the bovine serum albumin medium supported growth as well as the horse serum medium. Analysis of cholesterol, lipid phosphorus, and membrane protein showed the horse serum- and PPLO-grown cells to be indistinguishable, but the bovine serum albumin-grown cells were deficient in lipid phosphorus. The three cultures did not show markedly different fatty acid compositions, but, in all cases, the cultures preferentially incorporated palmitic acid and discriminated against linoleic acid. Cultures grown for different times from logarithmic growth through a degenerative phase showed relatively constant ratios of cholesterol/protein and lipid phosphorus/protein. Fatty acid composition was also relatively constant at the different stages. Adenosine triphosphatase and p-nitrophenyl phosphatase were mainly associated with the membrane, whereas reduced nicotinamide adenine dinucleotide oxidase was either readily removed or not associated with the membrane. The reduced nicotinamide adenine dinucleotide oxidase was inactivated at temperatures above 35 degrees C.", "contents": "Composition and enzyme activities of Spiroplasma citri membranes. Spiroplasma citri was cultured in three different media that supplied cholesterol and fatty acids from: (i) horse serum, (ii) pleuropneumonia-like organism (PPLO) serum fraction, or (iii) bovine serum albumin-fatty acid-cholesterol. The ability of PPLO serum fraction to support growth varied by lot number. Neither PPLO serum fraction nor the bovine serum albumin medium supported growth as well as the horse serum medium. Analysis of cholesterol, lipid phosphorus, and membrane protein showed the horse serum- and PPLO-grown cells to be indistinguishable, but the bovine serum albumin-grown cells were deficient in lipid phosphorus. The three cultures did not show markedly different fatty acid compositions, but, in all cases, the cultures preferentially incorporated palmitic acid and discriminated against linoleic acid. Cultures grown for different times from logarithmic growth through a degenerative phase showed relatively constant ratios of cholesterol/protein and lipid phosphorus/protein. Fatty acid composition was also relatively constant at the different stages. Adenosine triphosphatase and p-nitrophenyl phosphatase were mainly associated with the membrane, whereas reduced nicotinamide adenine dinucleotide oxidase was either readily removed or not associated with the membrane. The reduced nicotinamide adenine dinucleotide oxidase was inactivated at temperatures above 35 degrees C."}
{"id": "PMID:191433", "title": "Inhibition of aminoacyl-transfer ribonucleic acid synthetases and the regulation of amino acid biosynthetic enzymes in Neurospora crassa.", "content": "Growth conditions that result in the accumulation of the tryptophan intermediate indoleglycerol phosphate or of the histidine intermediate imidazoleglycerol phosphate cause mycelia of Neurospora crassa to exhibit an immediate and sustained increase in the differential rate at which the biosynthetic enzymes of the tryptophan, histidine, and arginine pathways are synthesized. These accumulated intermediates are shown to be inhibitors of the activity of aminoacyltransfer ribonucleic acid (tRNA) synthetases, as judged by an in vitro esterification assay. The tryptophan intermediate is shown to inhibit the charging of tryptophan, and the histidine intermediate is shown to inhibit charging of histidine. The inhibitions noted are consistent with the finding that the level of charged tRNATrp is decreased significantly in cells that have accumulated indoleglycerol phosphate and that of tRNAHis is decreased significantly in cells that have accumulated imidazoleglycerol phosphate. These results are interpreted as support for the involvement of aminoacyl-tRNA species in mediating cross-pathway regulation of the tryptophan, histidine, and arginine biosynthetic pathways as proposed in Lester's polyrepressor hypothesis (G. Lester, 1971). the correlations noted lead to the conclusion that Neurospora utilizes regulatory mechanisms that have the ability to react to changes in the level of charging of tRNA species.", "contents": "Inhibition of aminoacyl-transfer ribonucleic acid synthetases and the regulation of amino acid biosynthetic enzymes in Neurospora crassa. Growth conditions that result in the accumulation of the tryptophan intermediate indoleglycerol phosphate or of the histidine intermediate imidazoleglycerol phosphate cause mycelia of Neurospora crassa to exhibit an immediate and sustained increase in the differential rate at which the biosynthetic enzymes of the tryptophan, histidine, and arginine pathways are synthesized. These accumulated intermediates are shown to be inhibitors of the activity of aminoacyltransfer ribonucleic acid (tRNA) synthetases, as judged by an in vitro esterification assay. The tryptophan intermediate is shown to inhibit the charging of tryptophan, and the histidine intermediate is shown to inhibit charging of histidine. The inhibitions noted are consistent with the finding that the level of charged tRNATrp is decreased significantly in cells that have accumulated indoleglycerol phosphate and that of tRNAHis is decreased significantly in cells that have accumulated imidazoleglycerol phosphate. These results are interpreted as support for the involvement of aminoacyl-tRNA species in mediating cross-pathway regulation of the tryptophan, histidine, and arginine biosynthetic pathways as proposed in Lester's polyrepressor hypothesis (G. Lester, 1971). the correlations noted lead to the conclusion that Neurospora utilizes regulatory mechanisms that have the ability to react to changes in the level of charging of tRNA species."}
{"id": "PMID:191434", "title": "Isolation and characterization of Saccharomyces cerevisiae mutants defective in glycerol catabolism.", "content": "Mutants of the yeast Saccharomyces cerevisiae that are defective in the catabolism of glycerol were isolated, and two types of mutants were obtained. One type was deficient in glycerol kinase activity, whereas the other type was deficient in sn-glycerol 3-phosphate dehydrogenase activity. Genetic analysis indicated that each mutant strain owed its phenotype to a single nuclear mutation, and that the two mutations were complementary. The mutations were not linked to each other or to any of 10 loci tested. In addition, neither mutation was centromere linked. Possible mechanisms for the regulation of these enzymes were tested by growing the parental strain in the presence of various carbon sources.", "contents": "Isolation and characterization of Saccharomyces cerevisiae mutants defective in glycerol catabolism. Mutants of the yeast Saccharomyces cerevisiae that are defective in the catabolism of glycerol were isolated, and two types of mutants were obtained. One type was deficient in glycerol kinase activity, whereas the other type was deficient in sn-glycerol 3-phosphate dehydrogenase activity. Genetic analysis indicated that each mutant strain owed its phenotype to a single nuclear mutation, and that the two mutations were complementary. The mutations were not linked to each other or to any of 10 loci tested. In addition, neither mutation was centromere linked. Possible mechanisms for the regulation of these enzymes were tested by growing the parental strain in the presence of various carbon sources."}
{"id": "PMID:191435", "title": "Purification and some properties of phospholipase C (alpha-toxin) of Clostridium perfringens.", "content": "1. Phospholipase C[EC 3.1.4.3] was purified from the culture filtrate of Clostridium perfringens by successive chromatographies on CM-Sephadex, DEAE-Sephadex, and Sephadex G-100. During the purification it was noted that, beside the monomer form of the enzyme which was purified, a part of the enzyme existed in active polymerized forms. 2. The purified preparation gave a single band on polyacrylamide gel electrophoresis and gave a single precipitin line in immunodiffusion with the National Standard gas gangrene (C. perfringens) antitoxin, indicating the homogeneity of the preparation. 3. The specific lecithin-hydrolyzing activity of the purified preparation was comparable to that of a preparation obtained by affinity chromatography, which had the highest specific activity previously reported. 4. The molecular weight of the purified enzyme was estimated to be 43,000 by SDS-polyacryl-amide gel electrophoresis, although the same preparation gave a molecular weight of 31,000 as determined by gel filtration on Sephadex G-150. From this and the above finding that a part of the enzyme exists in active polymerized forms, the discrepancy among reported values for the molecular weight of C. perfringens phospholipase C can be accounted for. 5. For maximum hydrolytic activity toward lecithin, the enzyme required sodium deoxycholate (SDC) and Ca2+ ions. In the presence of 6 mM Ca2+, the optimal molar ratio of SDC to lecithin for maximal hydrolytic activity was about 0.5 for dipalmitoyl lecithin and about 1.0 for egg lecithin. The effects of various divalent cations on the enzymatic hydrolysis were also investigated. 6. The effects of sodium deoxycholate and Ca2+ ions on the enzymatic hydrolysis are discussed, based on their possible roles in mixed micelle formation.", "contents": "Purification and some properties of phospholipase C (alpha-toxin) of Clostridium perfringens. 1. Phospholipase C[EC 3.1.4.3] was purified from the culture filtrate of Clostridium perfringens by successive chromatographies on CM-Sephadex, DEAE-Sephadex, and Sephadex G-100. During the purification it was noted that, beside the monomer form of the enzyme which was purified, a part of the enzyme existed in active polymerized forms. 2. The purified preparation gave a single band on polyacrylamide gel electrophoresis and gave a single precipitin line in immunodiffusion with the National Standard gas gangrene (C. perfringens) antitoxin, indicating the homogeneity of the preparation. 3. The specific lecithin-hydrolyzing activity of the purified preparation was comparable to that of a preparation obtained by affinity chromatography, which had the highest specific activity previously reported. 4. The molecular weight of the purified enzyme was estimated to be 43,000 by SDS-polyacryl-amide gel electrophoresis, although the same preparation gave a molecular weight of 31,000 as determined by gel filtration on Sephadex G-150. From this and the above finding that a part of the enzyme exists in active polymerized forms, the discrepancy among reported values for the molecular weight of C. perfringens phospholipase C can be accounted for. 5. For maximum hydrolytic activity toward lecithin, the enzyme required sodium deoxycholate (SDC) and Ca2+ ions. In the presence of 6 mM Ca2+, the optimal molar ratio of SDC to lecithin for maximal hydrolytic activity was about 0.5 for dipalmitoyl lecithin and about 1.0 for egg lecithin. The effects of various divalent cations on the enzymatic hydrolysis were also investigated. 6. The effects of sodium deoxycholate and Ca2+ ions on the enzymatic hydrolysis are discussed, based on their possible roles in mixed micelle formation."}
{"id": "PMID:191436", "title": "Dihydropteridine reductase from bovine liver. Purification, crystallization, and isolation of a binary complex with NADH.", "content": "Dihydropteridine reductase [EC 1.6.99.7] was purified from bovine liver in 50% yield and crystallized. The physicochemical properties of the purified enzyme were quite similar to those of sheep liver dihydropteridine reductase. During the course of purification, however, the enzyme was found to be separated into 2 major peaks together with minor peaks by column chromatography on CM-Sephadex, and one of the major peaks was identified as a binary complex of the enzyme with NADH. The reductase-NADH complex was also prepared in vitro and crystallized. Upon addition of quinonoid-dihydropterin to the complex, NADH was oxidized and released from the enzyme. The amount of bound NADH was calculated to be 2 moles per mole of the reductase. The occurrence of the reductase-NADH was calculated to be 2 moles per mole of the reductase. The occurrence of the reductase-NADH complex in bovine liver extract as a predominant form was in accord with the pyridine nucleotide specificity for NADH as a coenzyme. The results further support the view that NADH is the natural coenzyme of this reductase.", "contents": "Dihydropteridine reductase from bovine liver. Purification, crystallization, and isolation of a binary complex with NADH. Dihydropteridine reductase [EC 1.6.99.7] was purified from bovine liver in 50% yield and crystallized. The physicochemical properties of the purified enzyme were quite similar to those of sheep liver dihydropteridine reductase. During the course of purification, however, the enzyme was found to be separated into 2 major peaks together with minor peaks by column chromatography on CM-Sephadex, and one of the major peaks was identified as a binary complex of the enzyme with NADH. The reductase-NADH complex was also prepared in vitro and crystallized. Upon addition of quinonoid-dihydropterin to the complex, NADH was oxidized and released from the enzyme. The amount of bound NADH was calculated to be 2 moles per mole of the reductase. The occurrence of the reductase-NADH was calculated to be 2 moles per mole of the reductase. The occurrence of the reductase-NADH complex in bovine liver extract as a predominant form was in accord with the pyridine nucleotide specificity for NADH as a coenzyme. The results further support the view that NADH is the natural coenzyme of this reductase."}
{"id": "PMID:191437", "title": "A complex of collagenase with low molecular weight inhibitors in the culture medium of embryonic chick skin explants.", "content": "Collagenase inhibitors with molecular weights of about 6,000 and 12,000 were isolated from latent chick skin collagenase treated with 3 M NaI and from the culture medium of embryonic skin explants. It is suggested that these inhibitors, which are possibly derived from connective tissue macromolecule metabolites, are candidates for regulating factors of collagenase activity in vivo.", "contents": "A complex of collagenase with low molecular weight inhibitors in the culture medium of embryonic chick skin explants. Collagenase inhibitors with molecular weights of about 6,000 and 12,000 were isolated from latent chick skin collagenase treated with 3 M NaI and from the culture medium of embryonic skin explants. It is suggested that these inhibitors, which are possibly derived from connective tissue macromolecule metabolites, are candidates for regulating factors of collagenase activity in vivo."}
{"id": "PMID:191438", "title": "Some enzymatic properties of peptidyl dipeptide hydrolase (angiotensin I-converting enzyme).", "content": "Peptidyldipeptide hydrolase [angiotensin I-converting enzyme, EC 3.4.15.1] was inhibited by inorganic and organic phosphorus compounds tested, except for beta-glycerophosphate, 5'-AMP, and 5'-ADP, at the reagent concentrations used. Orthophosphate and pyrophosphate nonspecifically inhibited the enzyme activity. The enzyme was also inhibited specifically by carboxylates. The degree of inhibition by aliphatic monocarboxylates increased in proportion to their chain length up to C14. Aromatic and omega-phenylalkylcarboxylates also inhibited the enzyme activity. The enzyme was noncompetitively inhibited by acetate, 3-phenylpropionate and laurate. The Ki's for acetate, 3-phenylpropionate, and laurate were 60, 3.3, and 2.5 mM, respectively.", "contents": "Some enzymatic properties of peptidyl dipeptide hydrolase (angiotensin I-converting enzyme). Peptidyldipeptide hydrolase [angiotensin I-converting enzyme, EC 3.4.15.1] was inhibited by inorganic and organic phosphorus compounds tested, except for beta-glycerophosphate, 5'-AMP, and 5'-ADP, at the reagent concentrations used. Orthophosphate and pyrophosphate nonspecifically inhibited the enzyme activity. The enzyme was also inhibited specifically by carboxylates. The degree of inhibition by aliphatic monocarboxylates increased in proportion to their chain length up to C14. Aromatic and omega-phenylalkylcarboxylates also inhibited the enzyme activity. The enzyme was noncompetitively inhibited by acetate, 3-phenylpropionate and laurate. The Ki's for acetate, 3-phenylpropionate, and laurate were 60, 3.3, and 2.5 mM, respectively."}
{"id": "PMID:191439", "title": "Multiple molecular forms of phosphoprotein phosphatase. Separation of four forms of the rabbit skeletal muscle enzyme.", "content": "Phosphoprotein phosphatase [phosphoprotein phosphohydrolase EC 3.1.3.16] in the soluble fraction of rabbit skeletal muscle, when assayed with phosphorylase a[EC 2.4.1.1] from rabbit skeletal muscle and phosphohistone as substrates, was resolved into three active fractions (Fractions I, II, and III in order of elution) by DEAE-cellulose column chromatography. Sucrose density gradient centrifugation showed that these fractions were composed of subfractions of different molecular size (I: 7.3S and 4S; II: 8S and 4S; III; 6.7S). Components with larger molecular size in the major fractions, II and III, were dissociated to a molecular size similar to that of the smallest component on freezing in the presence of mercaptoethanol. These results indicate that phosphoprotein phosphatase from skeletal muscle occurs in multiple forms very similar to those of the liver enzyme reported previously (Kobayashi, Kato and Sato (1975) Biochim. Biophys. Acta. 373, 343-355).", "contents": "Multiple molecular forms of phosphoprotein phosphatase. Separation of four forms of the rabbit skeletal muscle enzyme. Phosphoprotein phosphatase [phosphoprotein phosphohydrolase EC 3.1.3.16] in the soluble fraction of rabbit skeletal muscle, when assayed with phosphorylase a[EC 2.4.1.1] from rabbit skeletal muscle and phosphohistone as substrates, was resolved into three active fractions (Fractions I, II, and III in order of elution) by DEAE-cellulose column chromatography. Sucrose density gradient centrifugation showed that these fractions were composed of subfractions of different molecular size (I: 7.3S and 4S; II: 8S and 4S; III; 6.7S). Components with larger molecular size in the major fractions, II and III, were dissociated to a molecular size similar to that of the smallest component on freezing in the presence of mercaptoethanol. These results indicate that phosphoprotein phosphatase from skeletal muscle occurs in multiple forms very similar to those of the liver enzyme reported previously (Kobayashi, Kato and Sato (1975) Biochim. Biophys. Acta. 373, 343-355)."}
{"id": "PMID:191440", "title": "Two types of sarcoplasmic reticulum-orthophosphate interactions observed with dye probe.", "content": "The interaction of Pi with sarcoplasmic reticulum (SR) isolated from rabbit skeletal muscle was studied using bromocresol purple (BCP) as a probe and a dual-wavelength spectrophotometer. Two kinds of absorption-intensity changes controlled by a low concentration of Ca2+ (greater than 10(-6)M) were observed after addition of Pi; an increase phase (in the presence of Ca2+), and a decrease phase (in the presence of EGTA). The increase phase was rapid, Ca2+-dependent, Mg2+-enhanced (depressed by high Mg2+ concentration) and not inhibited by PCMB and was suggested to reflect the formation of an SR-Pi complex. The decrease phase was slower than the increase phase, and was strongly inhibited by the low concentration of Ca2+. It required Mg2+, and was completely inhibited by p-chloromercuribenzoate or deoxycholate. It was suggested to reflect the formation of SR-Pi (phosphorylated protein). ATP inhibited this phase by converting it completely to an SR-MgATP phase. PPi was effective for inducing the decrease phase but PPPi was not. From measurements of these phases, the association constants of the SR-Pi complex and SR-Pi at pH 8.8 in the reaction scheme, SR + Pi in equilibrium SR-Pi in equilibrium SR-Pi, were calculated as 5.4 X 10 M-1 and 1.8 X 10(3) M-1, respectively. From the completely different responses of SR-Pi and SR-Pi observed with BCP a marked difference in the conformations of these enzyme states was suggested.", "contents": "Two types of sarcoplasmic reticulum-orthophosphate interactions observed with dye probe. The interaction of Pi with sarcoplasmic reticulum (SR) isolated from rabbit skeletal muscle was studied using bromocresol purple (BCP) as a probe and a dual-wavelength spectrophotometer. Two kinds of absorption-intensity changes controlled by a low concentration of Ca2+ (greater than 10(-6)M) were observed after addition of Pi; an increase phase (in the presence of Ca2+), and a decrease phase (in the presence of EGTA). The increase phase was rapid, Ca2+-dependent, Mg2+-enhanced (depressed by high Mg2+ concentration) and not inhibited by PCMB and was suggested to reflect the formation of an SR-Pi complex. The decrease phase was slower than the increase phase, and was strongly inhibited by the low concentration of Ca2+. It required Mg2+, and was completely inhibited by p-chloromercuribenzoate or deoxycholate. It was suggested to reflect the formation of SR-Pi (phosphorylated protein). ATP inhibited this phase by converting it completely to an SR-MgATP phase. PPi was effective for inducing the decrease phase but PPPi was not. From measurements of these phases, the association constants of the SR-Pi complex and SR-Pi at pH 8.8 in the reaction scheme, SR + Pi in equilibrium SR-Pi in equilibrium SR-Pi, were calculated as 5.4 X 10 M-1 and 1.8 X 10(3) M-1, respectively. From the completely different responses of SR-Pi and SR-Pi observed with BCP a marked difference in the conformations of these enzyme states was suggested."}
{"id": "PMID:191441", "title": "Relationship between tubulin SH groups and bound guanine nucleotides.", "content": "Guanine nucleotides bound to both the non-exchangeable sites (N sites) and exchangeable sites (E sites) of tubulin were completely released after 7 moles of SH groups per tubulin subunit (55,000 molecular weight) had reacted with PCMPS. The blockage of 2 moles of SH groups in the glycerol-reassembly buffer or 1 mole of SH groups in glycerol-free reassembly buffer resulted in complete loss of tubulin polymerizability. However, under both sets of experimental conditions, the amount of guanine nucleotides released from the E sites was less than 8% and the loss of total guanine nucleotides was only 5%. Addition of GSH did not induce reassociation of released guanine nucleotides, although it restored tubulin polymerizability. These results indicate that the loss of tubulin polymerizability on blockage of the SH groups was not due to dissociation of bound guanine nucleotides and that the binding sites of the nucleotides were independent of the SH groups in tubulin required for polymerization. Furthermore, blockage of SH groups did not change the ratio of GTP to GDP bound to tubulin.", "contents": "Relationship between tubulin SH groups and bound guanine nucleotides. Guanine nucleotides bound to both the non-exchangeable sites (N sites) and exchangeable sites (E sites) of tubulin were completely released after 7 moles of SH groups per tubulin subunit (55,000 molecular weight) had reacted with PCMPS. The blockage of 2 moles of SH groups in the glycerol-reassembly buffer or 1 mole of SH groups in glycerol-free reassembly buffer resulted in complete loss of tubulin polymerizability. However, under both sets of experimental conditions, the amount of guanine nucleotides released from the E sites was less than 8% and the loss of total guanine nucleotides was only 5%. Addition of GSH did not induce reassociation of released guanine nucleotides, although it restored tubulin polymerizability. These results indicate that the loss of tubulin polymerizability on blockage of the SH groups was not due to dissociation of bound guanine nucleotides and that the binding sites of the nucleotides were independent of the SH groups in tubulin required for polymerization. Furthermore, blockage of SH groups did not change the ratio of GTP to GDP bound to tubulin."}
{"id": "PMID:191442", "title": "The structure and function of ribonuclease T1. XXII. Tryptic cleavages of the single lysyl and arginyl bonds in ribonuclease T1.", "content": "1. When ribonuclease T1 [EC 3.1.4.8] was treated with trypsin [EC 3.4.21.4] at pH 7.5 and 37 degrees, activity was lost fairly slowly. At higher temperatures, however, the rate of inactivation was markedly accelerated. The half life of the activity was about 2.5 h at 50 degrees and 1 h at 60 degrees. 3'-GMP and guanosine protected the enzyme significantly from tryptic inactivation. 2. Upon tryptic digestion at 50 degrees, the Lys-Tyr (41-42) and Arg-Val (77-78) bonds were cleaved fairly specifically, yielding two peptide fragments. One was a 36 residue peptide comprizing residues 42 to 77. The other was a 68 residue peptide composed of two peptide chains cross-linked by a disulfide bond between half-cystines -6 and -103, comprizing residues 1 to 41 and 78 to 104. 3. When the trinitrophenylated enzyme, in which the alpha-amino group of alanine-1 and the episolone-amino group of lysine 41 were selectively modified, was treated with trypsin at 37 degrees, the activity was lost fairly rapidly with a half life of about 4 h. In this case, tryptic hydrolysis occurred fairly selectively at the single Arg-Val bond. Thus the enzyme could be inactivated by cleavage of a single peptide bond in the molecule, an indication of the importance of the peptide region involving the single arginine residue at position 77 in the activity of ribonuclease T1.", "contents": "The structure and function of ribonuclease T1. XXII. Tryptic cleavages of the single lysyl and arginyl bonds in ribonuclease T1. 1. When ribonuclease T1 [EC 3.1.4.8] was treated with trypsin [EC 3.4.21.4] at pH 7.5 and 37 degrees, activity was lost fairly slowly. At higher temperatures, however, the rate of inactivation was markedly accelerated. The half life of the activity was about 2.5 h at 50 degrees and 1 h at 60 degrees. 3'-GMP and guanosine protected the enzyme significantly from tryptic inactivation. 2. Upon tryptic digestion at 50 degrees, the Lys-Tyr (41-42) and Arg-Val (77-78) bonds were cleaved fairly specifically, yielding two peptide fragments. One was a 36 residue peptide comprizing residues 42 to 77. The other was a 68 residue peptide composed of two peptide chains cross-linked by a disulfide bond between half-cystines -6 and -103, comprizing residues 1 to 41 and 78 to 104. 3. When the trinitrophenylated enzyme, in which the alpha-amino group of alanine-1 and the episolone-amino group of lysine 41 were selectively modified, was treated with trypsin at 37 degrees, the activity was lost fairly rapidly with a half life of about 4 h. In this case, tryptic hydrolysis occurred fairly selectively at the single Arg-Val bond. Thus the enzyme could be inactivated by cleavage of a single peptide bond in the molecule, an indication of the importance of the peptide region involving the single arginine residue at position 77 in the activity of ribonuclease T1."}
{"id": "PMID:191443", "title": "Selective solubilization of apolipoproteins from hen's egg yolk very low density lipoprotein with guanidine hydrochloride and urea.", "content": "The selective solubilization of apo-very low density lipoprotein (apo VLDL) of hen's egg yolk was achieved from intact VLDL with guanidine hydrochloride (GuHCl) or urea. The amount of extracted apoVLDL increased with increase of the reagent concentration. GuHCl was more effective than urea and more than 60% of apoVLDL was solubilized with 6 M GuHCl. Previously we reported the presence of five major apoVLDL components, GPI, ApoA, GPII, ApoB, and ApoC in order of size, and found that GPI and GPII were periodic acid-Schiff staining positive, while ApoA, ApoB, and ApoC were negative. With GuHCl or urea, GPI and GPII were easily solubilized, while ApoA and ApoB could not be extracted. The solubilized apoVLDL was rich in carbohydrates, especially sialic acid, compared with the residual apoVLDL. However, only slight differences in amino acid compositon were found between the soluble and the residual apoVLDL. After the partial removal of apoVLDL with GuHCl or urea, VLDL retained its particulate nature, and no destruction of the lipid core was observed. These results were interpreted as indicating that the release of apoVLDL with GuHCl or urea occurred from the surface of the VLDL particle and that the selectively solubilized apoVLDL fractions, such as GPI and GPII, were weakly bound to lipids on the surface of VLDL, while ApoA and ApoB were tightly associated with the VLDL particle.", "contents": "Selective solubilization of apolipoproteins from hen's egg yolk very low density lipoprotein with guanidine hydrochloride and urea. The selective solubilization of apo-very low density lipoprotein (apo VLDL) of hen's egg yolk was achieved from intact VLDL with guanidine hydrochloride (GuHCl) or urea. The amount of extracted apoVLDL increased with increase of the reagent concentration. GuHCl was more effective than urea and more than 60% of apoVLDL was solubilized with 6 M GuHCl. Previously we reported the presence of five major apoVLDL components, GPI, ApoA, GPII, ApoB, and ApoC in order of size, and found that GPI and GPII were periodic acid-Schiff staining positive, while ApoA, ApoB, and ApoC were negative. With GuHCl or urea, GPI and GPII were easily solubilized, while ApoA and ApoB could not be extracted. The solubilized apoVLDL was rich in carbohydrates, especially sialic acid, compared with the residual apoVLDL. However, only slight differences in amino acid compositon were found between the soluble and the residual apoVLDL. After the partial removal of apoVLDL with GuHCl or urea, VLDL retained its particulate nature, and no destruction of the lipid core was observed. These results were interpreted as indicating that the release of apoVLDL with GuHCl or urea occurred from the surface of the VLDL particle and that the selectively solubilized apoVLDL fractions, such as GPI and GPII, were weakly bound to lipids on the surface of VLDL, while ApoA and ApoB were tightly associated with the VLDL particle."}
{"id": "PMID:191444", "title": "Induction of ornithine decarboxylase in cultured mouse L cells. II. Effects of additions of amino acids and serum.", "content": "Induction of ornithine decarboxylase [EC 4.1.1.17] (ODC) in mouse L cells by components of the culture medium was investigated. It was found that further addition of amino acid  mixture, but not of calf serum, to confluent cells of 5 day culture induced ODC and that this induction was accelerated by actinactinomycin D. In salt solution, addition of either amino acids or serum alone did not cause full induction, but addition of both together did. This induction, in contrast, was inhibited by actinomycin D. Induction by insulin, but not by cyclic AMP, was enhanced by a higher concentration of amino acids. These results can be explained by supposing that in non-growing cells there is stable RNA which is involved in ODC induction, possibly mRNA of ODC, and that the observed induction is caused by inhibition of enzyme degradation and accelerated translation, while in growing cells this RNA is unstable and ODC induction is controlled at the level of transcription.", "contents": "Induction of ornithine decarboxylase in cultured mouse L cells. II. Effects of additions of amino acids and serum. Induction of ornithine decarboxylase [EC 4.1.1.17] (ODC) in mouse L cells by components of the culture medium was investigated. It was found that further addition of amino acid  mixture, but not of calf serum, to confluent cells of 5 day culture induced ODC and that this induction was accelerated by actinactinomycin D. In salt solution, addition of either amino acids or serum alone did not cause full induction, but addition of both together did. This induction, in contrast, was inhibited by actinomycin D. Induction by insulin, but not by cyclic AMP, was enhanced by a higher concentration of amino acids. These results can be explained by supposing that in non-growing cells there is stable RNA which is involved in ODC induction, possibly mRNA of ODC, and that the observed induction is caused by inhibition of enzyme degradation and accelerated translation, while in growing cells this RNA is unstable and ODC induction is controlled at the level of transcription."}
{"id": "PMID:191445", "title": "Properties of immunoreactive glucagon fractions of canine stomach and pancreas.", "content": "The present study was designed to identify the physicochemical, immunologic, and biologic properties of the immunoreactive glucagon (IRG) moieties of canine gastric fundus and to compare them with those of the canine pancreas. Acid-alcohol extracts of the gastric fundus and pancreas of dogs were subjected to Bio-Gel P-10 chromatography, The elution profiles of extracts of both organs revealed IRG peaks in the Mr = 2,000 3,500, and 9,000 zones; in the gastric extracts, a void volume peak was also present. On the basis of Sephadex G-150 rechromatography and sucrose density gradient ultracentrifugation the latter IRG was estimated to have a Mr = 65,000. Incubation of fundic IRG65,000 in 8 M urea failed to alter its elution position. Its pI was 6.4, while fundic IRG3,500 had a pI of 6.15 and pancreatic glucagon 6.25. Fundic IRG9,000 had a pI of 4.5 and pancreatic IRG9,000 4.65. Dilution curves of these three fundic and two pancreatic IRGs were parallel to crystalline beef-pork glucagon. The glycogenolytic activity of fundic IRG3,500 and IRG65,000, measured in the isolated rat liver system, was not different from that of immunoequivalent amounts of dog pancreatic glucagon or crystalline beef-pork glucagon. Both fundic and pancreatic IRG9,000 were devoid of glycogenolytic activity and lacker adenylate cyclase stimulating activity and 125I-glucagon displacing activity when tested on partially purified rat liver membranes. Fundic IRG65,000, however, stimulated adenylate cyclase and displaced 125I-glucagon to the same degree as immunoequivalent amounts of pancreatic glucagon. Fundic IRG3,500 was more active than pancreatic glucagon in stimulating adenylate cyclase activity. This was not clearly attributable to differences in binding to liver cell membranes.", "contents": "Properties of immunoreactive glucagon fractions of canine stomach and pancreas. The present study was designed to identify the physicochemical, immunologic, and biologic properties of the immunoreactive glucagon (IRG) moieties of canine gastric fundus and to compare them with those of the canine pancreas. Acid-alcohol extracts of the gastric fundus and pancreas of dogs were subjected to Bio-Gel P-10 chromatography, The elution profiles of extracts of both organs revealed IRG peaks in the Mr = 2,000 3,500, and 9,000 zones; in the gastric extracts, a void volume peak was also present. On the basis of Sephadex G-150 rechromatography and sucrose density gradient ultracentrifugation the latter IRG was estimated to have a Mr = 65,000. Incubation of fundic IRG65,000 in 8 M urea failed to alter its elution position. Its pI was 6.4, while fundic IRG3,500 had a pI of 6.15 and pancreatic glucagon 6.25. Fundic IRG9,000 had a pI of 4.5 and pancreatic IRG9,000 4.65. Dilution curves of these three fundic and two pancreatic IRGs were parallel to crystalline beef-pork glucagon. The glycogenolytic activity of fundic IRG3,500 and IRG65,000, measured in the isolated rat liver system, was not different from that of immunoequivalent amounts of dog pancreatic glucagon or crystalline beef-pork glucagon. Both fundic and pancreatic IRG9,000 were devoid of glycogenolytic activity and lacker adenylate cyclase stimulating activity and 125I-glucagon displacing activity when tested on partially purified rat liver membranes. Fundic IRG65,000, however, stimulated adenylate cyclase and displaced 125I-glucagon to the same degree as immunoequivalent amounts of pancreatic glucagon. Fundic IRG3,500 was more active than pancreatic glucagon in stimulating adenylate cyclase activity. This was not clearly attributable to differences in binding to liver cell membranes."}
{"id": "PMID:191446", "title": "Mechanism of regulation of adenylate cyclase activity in human polymorphonuclear leukocytes by calcium, guanosyl nucleotides, and positive effectors.", "content": "This study presents the results of a kinetic investigation of adenylate cyclase in human polymorphonuclear leukocytes. In the presence of a saturating concentration of substrate (1 mM), the basal activity was increased severalfold by increasing Mg2+ from 1 to 25 mM. A Hill coefficient of 1.9 was obtained for Mg2+ or ATP. The data suggest cooperative interactions between the substrate binding sites in the neutrophil adenylate cyclase complex. It has been observed that guanyl-5'-yl imidodiphosphate (Gpp(NH)p) (S0.5 = 10 MUM) significantly increased and Ca2+ (S0.5 = 0.5 MM) significantly decreased only the Vmax without affecting the Hill coefficient or S0.5 for ATP. The Hill coefficients for Ca2+ or Gpp(NH)p were 0.9 and 0.8, respectively. The Hill coefficient for Ca2+ was not changed by the increased Gpp(NH)p concentrations. It appears that neutrophil adenylate cyclase has distinct binding sites for Gpp(NH)p and Ca2+, one for each compond. The binding of ligands is not changed by the other effectors and the action is directed only toward the Vmax of the enzyme. The stimulatory action of positive effectors (prostaglandin E1, isoproterenol, histamine) was enhanced by Gpp(NH)p and depressed by Ca2+. No preferential stimulation by Gpp(NH)p nor inhibition by Ca2+ of the action of the positive effectors has been found. The data suggests that only one type of catalytic subunit responds to the action of several positive effectors. Extracellular Gpp(NH)p or Ca2+ do not affect the cyclic adenosine 3':5'-monophosphate (cAMP) level in whole neutrophils and the effect of positive effectors on cAMP production is also not significantly changed by 5 mM Ca2+ or 0.1 mM Gpp(NH)p. Ionophore A23187 in the presence of 5 mM Ca2+ enhances Ca2+ entry into cells and decreases the basal cAMP formation. It appears that Gpp(NH)p or Ca2+ act only at the intracellular site of the adenylate cyclase complex.", "contents": "Mechanism of regulation of adenylate cyclase activity in human polymorphonuclear leukocytes by calcium, guanosyl nucleotides, and positive effectors. This study presents the results of a kinetic investigation of adenylate cyclase in human polymorphonuclear leukocytes. In the presence of a saturating concentration of substrate (1 mM), the basal activity was increased severalfold by increasing Mg2+ from 1 to 25 mM. A Hill coefficient of 1.9 was obtained for Mg2+ or ATP. The data suggest cooperative interactions between the substrate binding sites in the neutrophil adenylate cyclase complex. It has been observed that guanyl-5'-yl imidodiphosphate (Gpp(NH)p) (S0.5 = 10 MUM) significantly increased and Ca2+ (S0.5 = 0.5 MM) significantly decreased only the Vmax without affecting the Hill coefficient or S0.5 for ATP. The Hill coefficients for Ca2+ or Gpp(NH)p were 0.9 and 0.8, respectively. The Hill coefficient for Ca2+ was not changed by the increased Gpp(NH)p concentrations. It appears that neutrophil adenylate cyclase has distinct binding sites for Gpp(NH)p and Ca2+, one for each compond. The binding of ligands is not changed by the other effectors and the action is directed only toward the Vmax of the enzyme. The stimulatory action of positive effectors (prostaglandin E1, isoproterenol, histamine) was enhanced by Gpp(NH)p and depressed by Ca2+. No preferential stimulation by Gpp(NH)p nor inhibition by Ca2+ of the action of the positive effectors has been found. The data suggests that only one type of catalytic subunit responds to the action of several positive effectors. Extracellular Gpp(NH)p or Ca2+ do not affect the cyclic adenosine 3':5'-monophosphate (cAMP) level in whole neutrophils and the effect of positive effectors on cAMP production is also not significantly changed by 5 mM Ca2+ or 0.1 mM Gpp(NH)p. Ionophore A23187 in the presence of 5 mM Ca2+ enhances Ca2+ entry into cells and decreases the basal cAMP formation. It appears that Gpp(NH)p or Ca2+ act only at the intracellular site of the adenylate cyclase complex."}
{"id": "PMID:191447", "title": "Incorporation of dietary cis and trans isomers of octadecenoate in lipid classes of liver and hepatoma.", "content": "Groups of rats bearing Morris minimal deviation hepatoma 7288CTC were fed a fat-free diet supplemented with either 0.5% safflower oil (diet A), 15% safflower oil or free acids (diets Band C), or 15% safflower oil or free safflower fatty acids (diet D) for 4 weeks. A group of normal rats was also fed diet D. Triglycerides, cholesteryl esters, phosphatidylcholines, and phosphatidylethanolamines isolated from livers and hepatomas of animals on each diet were analyzed quantitatively for positional isomers in the cis- and trans-octadecenoate fractions. When sufficient samples could be obtained, the cis- and trans-hexadecenoate fractions were also analyzed. Plasma from normal rats on diet D was analyzed in the same manner. The octadecenoate fractions of all hepatoma and liver lipid classes from animals fed diets A, B, and C were greater than 95% the cis isomers. Trans isomers accounted for approximately 15, 30, 50, and 70% of the octadecenoate fractions isolated from liver triglycerides, cholesteryl esters, phosphatidylcholines, and phosphatidylethanolamines, respectively, of animals fed diet D. In contrast, all hepatoma lipid classes from animals on diet D contained the same approximate percentage of trans isomers (15 to 20%). Oleic and vaccenic acids were the major positional cis-octadecenoate isomers of all liver and hepatoma lipid classes from animals fed diets A, B, and C. The ratios of oleic to vaccenic, unaffected by diets A, B, and C, differed for each lipid class in liver, but the ratios were similar for the two hepatoma neutral lipid classes and for the two phospholipid classes. The cis-octadecenoate fractions from all liver and hepatoma lipid classes of animals fed diet D consisted predominantly of the delta9, delta11, and delta12 isomers. The cis delta10 isomer, which was a major isomer of the diet, was almost excluded from liver, hepatoma, and plasma lipids. The positional isomers of the trans-octadecenoate fractions from liver and hepatoma triglycerides and cholesteryl esters exhibited the same approximate distribution as the trans fatty acids of diet D. In contrast, the 10-trans-octadecenoate, like 10-cis-octadecenoate, was almost excluded from the phospholipids of liver and plasma. Unlike liver, the hepatoma phospholipids contained 10-trans-octadecenoate at approximately half the percentage of neutral lipids. Because diet D contained no hexadecenoic fatty acids, the occurrence of trans-hexadecenoate isomers in liver and plasma lipids indicated a chain shortening process. Predominance of the 8-trans-hexadecenoate isomer indicated a preference of the 10-trans-octadecenoate isomer for chain shortening.", "contents": "Incorporation of dietary cis and trans isomers of octadecenoate in lipid classes of liver and hepatoma. Groups of rats bearing Morris minimal deviation hepatoma 7288CTC were fed a fat-free diet supplemented with either 0.5% safflower oil (diet A), 15% safflower oil or free acids (diets Band C), or 15% safflower oil or free safflower fatty acids (diet D) for 4 weeks. A group of normal rats was also fed diet D. Triglycerides, cholesteryl esters, phosphatidylcholines, and phosphatidylethanolamines isolated from livers and hepatomas of animals on each diet were analyzed quantitatively for positional isomers in the cis- and trans-octadecenoate fractions. When sufficient samples could be obtained, the cis- and trans-hexadecenoate fractions were also analyzed. Plasma from normal rats on diet D was analyzed in the same manner. The octadecenoate fractions of all hepatoma and liver lipid classes from animals fed diets A, B, and C were greater than 95% the cis isomers. Trans isomers accounted for approximately 15, 30, 50, and 70% of the octadecenoate fractions isolated from liver triglycerides, cholesteryl esters, phosphatidylcholines, and phosphatidylethanolamines, respectively, of animals fed diet D. In contrast, all hepatoma lipid classes from animals on diet D contained the same approximate percentage of trans isomers (15 to 20%). Oleic and vaccenic acids were the major positional cis-octadecenoate isomers of all liver and hepatoma lipid classes from animals fed diets A, B, and C. The ratios of oleic to vaccenic, unaffected by diets A, B, and C, differed for each lipid class in liver, but the ratios were similar for the two hepatoma neutral lipid classes and for the two phospholipid classes. The cis-octadecenoate fractions from all liver and hepatoma lipid classes of animals fed diet D consisted predominantly of the delta9, delta11, and delta12 isomers. The cis delta10 isomer, which was a major isomer of the diet, was almost excluded from liver, hepatoma, and plasma lipids. The positional isomers of the trans-octadecenoate fractions from liver and hepatoma triglycerides and cholesteryl esters exhibited the same approximate distribution as the trans fatty acids of diet D. In contrast, the 10-trans-octadecenoate, like 10-cis-octadecenoate, was almost excluded from the phospholipids of liver and plasma. Unlike liver, the hepatoma phospholipids contained 10-trans-octadecenoate at approximately half the percentage of neutral lipids. Because diet D contained no hexadecenoic fatty acids, the occurrence of trans-hexadecenoate isomers in liver and plasma lipids indicated a chain shortening process. Predominance of the 8-trans-hexadecenoate isomer indicated a preference of the 10-trans-octadecenoate isomer for chain shortening."}
{"id": "PMID:191448", "title": "Magnetic resonance studies of the manganese guanosine di- and triphosphate complexes with elongation factor Tu.", "content": "Analysis of titration data of EF-Tu-GDP with Mn(II) where free and bound Mn(II) were determined by proton relaxation rate of water (PRR) yields one tight Mn(II) binding site and a value of 2 muM for the dissociation constant of Mn(II) from the EF-Tu-MnGDP complex, K'A. The dissociation constant of manganese nucleotide from the ternary EF-Tu-MnGDP complex, K2, 0.2 muM, was derived from the known value of Ks, the dissociation constant for the binary EF-Tu-GDP complex, and the titration data of the ternary complex with excess GDP as titrant. The apparent number, n, of rapidly exchanging water ligands coordinated to bound Mn(II) in the ternary complex EF-Tu-MnGDP is estimated from the frequency dependence of the PRR of the complex to be approximately 1. The value of n and the values of PRR enhancements, epsilont = 4.3 for EF-Tu-MnGDP at 21 degrees, 24.3 MHZ and epsilont = 4.1 for the ternary GTP complex, are unusually low for protein-Mn-nucleotide complexes. The antibiotic X5108 which induces GTPase activity in EF-Tu-MgGTP was shown to bind stoichiometrically to EF-Tu-MnGDP and thereby change the PRR enhancement of the complex from 4.3 to 7.4. The characteristic broad lines in the EPR spectra of Mn(II) nucleotides are strikingly narrowed upon binding of Mn(II) nucleotides to EF-Tu. The long electron spin relaxation times inferred from the EPR spectra indicate a limited access of solvent water to the first coordination sphere of Mn(II) in its EF-Tu-nucleotide complexes. The frequency dependence of the PRR indicates that the electron spin relaxation time, T1e, is the dominant process modulating the Mn(II)-H2O interaction of the EF-Tu-MnGDP complex and consequently determines the correlation time. The value of T1e, estimated from the PRR experiments to be 2.5 ns at 21 degrees, is consistent with the lower limit of T1e obtained from the line widths of the EPR spectrum of the complex. Upon binding of a stoichiometric quantity of the antibiotic X5108, the EPR spectrum of EF-Tu-MnGDP is severely broadened indicating greater access of solvent water to the manganese coordination sphere, i.e. an opening of the nucleotide binding site as already suggested by the increased PRR enhancement.", "contents": "Magnetic resonance studies of the manganese guanosine di- and triphosphate complexes with elongation factor Tu. Analysis of titration data of EF-Tu-GDP with Mn(II) where free and bound Mn(II) were determined by proton relaxation rate of water (PRR) yields one tight Mn(II) binding site and a value of 2 muM for the dissociation constant of Mn(II) from the EF-Tu-MnGDP complex, K'A. The dissociation constant of manganese nucleotide from the ternary EF-Tu-MnGDP complex, K2, 0.2 muM, was derived from the known value of Ks, the dissociation constant for the binary EF-Tu-GDP complex, and the titration data of the ternary complex with excess GDP as titrant. The apparent number, n, of rapidly exchanging water ligands coordinated to bound Mn(II) in the ternary complex EF-Tu-MnGDP is estimated from the frequency dependence of the PRR of the complex to be approximately 1. The value of n and the values of PRR enhancements, epsilont = 4.3 for EF-Tu-MnGDP at 21 degrees, 24.3 MHZ and epsilont = 4.1 for the ternary GTP complex, are unusually low for protein-Mn-nucleotide complexes. The antibiotic X5108 which induces GTPase activity in EF-Tu-MgGTP was shown to bind stoichiometrically to EF-Tu-MnGDP and thereby change the PRR enhancement of the complex from 4.3 to 7.4. The characteristic broad lines in the EPR spectra of Mn(II) nucleotides are strikingly narrowed upon binding of Mn(II) nucleotides to EF-Tu. The long electron spin relaxation times inferred from the EPR spectra indicate a limited access of solvent water to the first coordination sphere of Mn(II) in its EF-Tu-nucleotide complexes. The frequency dependence of the PRR indicates that the electron spin relaxation time, T1e, is the dominant process modulating the Mn(II)-H2O interaction of the EF-Tu-MnGDP complex and consequently determines the correlation time. The value of T1e, estimated from the PRR experiments to be 2.5 ns at 21 degrees, is consistent with the lower limit of T1e obtained from the line widths of the EPR spectrum of the complex. Upon binding of a stoichiometric quantity of the antibiotic X5108, the EPR spectrum of EF-Tu-MnGDP is severely broadened indicating greater access of solvent water to the manganese coordination sphere, i.e. an opening of the nucleotide binding site as already suggested by the increased PRR enhancement."}
{"id": "PMID:191449", "title": "Proteolytic activation of rat liver adenylate cyclase by a contaminant of crude collagenase from Clostridium histolyticum.", "content": "Treatment of rat liver plasma membranes with various commercial preparations of crude collagenase from Clostridium histolyticum at concentrations as low as 1 mug/ml, resulted in activation of the adenylate cyclase system. Maximal activation occurred at 50 to 100 mug/ml of collagenase, and promoted a 2- to 3-fold increase in the basal activity as well as in the activities stimulated by catecholamines, glucagon, fluoride, or GTP. This was due to an increase in the maximal velocity of the cyclizing reaction without any increase in the affinity of the enzyme for its substrate. Treatment of plasma membranes with crude collagenase did not induce gross structural modifications as judged by electron microscopic examination. 5'-Nucleotidase activity was slightly inhibited and ATPase activity remained unaffected. The stimulatory substance was nondialyzable, thermolabile, and inhibited by both EDTA and -SH reagents, thus appearing to be a protein. The following observations suggest the effects observed were due to other protease(s) present in crude collagenase: (a) only crude collagenase was active on liver adenylate cyclase: treatment with purified collagenase from C. histolyticum or from Achromobacter iophagus gave no stimulation; (b) the stimulatory activity was irreversible since washing of the membranes after treatment was without effect; (c) crude collagenase contained no lecithinase or sphingomyelinase activity under our conditions of adenylate cyclase assay; (d) after chromatography on Sephadex G-100, the activator appeared as a peak in the 30,000-dalton region and was clearly separated from the collagenase and clostripain peaks, but coincident with elastolytic and caseinolytic activities; (e) the effect of crude collagenase could be prevented by addition of elastin in vitro and was mimicked by purified elastase from hog pancreas. It remains to be seen whether the effects observed result from an increase in the catalytic constant of adenylate cyclase, or an unmasking of new catalytic sites.", "contents": "Proteolytic activation of rat liver adenylate cyclase by a contaminant of crude collagenase from Clostridium histolyticum. Treatment of rat liver plasma membranes with various commercial preparations of crude collagenase from Clostridium histolyticum at concentrations as low as 1 mug/ml, resulted in activation of the adenylate cyclase system. Maximal activation occurred at 50 to 100 mug/ml of collagenase, and promoted a 2- to 3-fold increase in the basal activity as well as in the activities stimulated by catecholamines, glucagon, fluoride, or GTP. This was due to an increase in the maximal velocity of the cyclizing reaction without any increase in the affinity of the enzyme for its substrate. Treatment of plasma membranes with crude collagenase did not induce gross structural modifications as judged by electron microscopic examination. 5'-Nucleotidase activity was slightly inhibited and ATPase activity remained unaffected. The stimulatory substance was nondialyzable, thermolabile, and inhibited by both EDTA and -SH reagents, thus appearing to be a protein. The following observations suggest the effects observed were due to other protease(s) present in crude collagenase: (a) only crude collagenase was active on liver adenylate cyclase: treatment with purified collagenase from C. histolyticum or from Achromobacter iophagus gave no stimulation; (b) the stimulatory activity was irreversible since washing of the membranes after treatment was without effect; (c) crude collagenase contained no lecithinase or sphingomyelinase activity under our conditions of adenylate cyclase assay; (d) after chromatography on Sephadex G-100, the activator appeared as a peak in the 30,000-dalton region and was clearly separated from the collagenase and clostripain peaks, but coincident with elastolytic and caseinolytic activities; (e) the effect of crude collagenase could be prevented by addition of elastin in vitro and was mimicked by purified elastase from hog pancreas. It remains to be seen whether the effects observed result from an increase in the catalytic constant of adenylate cyclase, or an unmasking of new catalytic sites."}
{"id": "PMID:191450", "title": "Biosynthesis of ferritin in rat hepatoma cells and rat livers. I. Synthesis and assembly of protein subunits of ferritin.", "content": "Cell fractions were prepared from ACI rat livers and from rat hepatoma cell clone M-5123-C1. Radioimmunoassays of ferritin and of its protein subunits in various cell fractions after biosynthetic labeling with [14C]leucine were done by means of ferritin-specific and subunit-specific rabbit antibody. In both ACI rat livers and M-5123-C1 hepatoma cells free polyribosomes synthesized approximately 81% of the protein subunits of ferritin, and membrane-bound polyribosomes synthesized the rest. In both polyribosomal fractions, [14C]leucine-labeled subunits were detected earlier than [14C]leucine-labeled ferritin and apoferritin (5 min as against 30 min after initiation of a pulse). Time sequence studies of the shifts of biosynthetically labeled subunits and ferritin through different cell compartments provided evidence for vectorial transport of subunits and of ferritin, the direction of transport being from the two polyribosomal systems to the smooth membrane compartment and to the cytosol.", "contents": "Biosynthesis of ferritin in rat hepatoma cells and rat livers. I. Synthesis and assembly of protein subunits of ferritin. Cell fractions were prepared from ACI rat livers and from rat hepatoma cell clone M-5123-C1. Radioimmunoassays of ferritin and of its protein subunits in various cell fractions after biosynthetic labeling with [14C]leucine were done by means of ferritin-specific and subunit-specific rabbit antibody. In both ACI rat livers and M-5123-C1 hepatoma cells free polyribosomes synthesized approximately 81% of the protein subunits of ferritin, and membrane-bound polyribosomes synthesized the rest. In both polyribosomal fractions, [14C]leucine-labeled subunits were detected earlier than [14C]leucine-labeled ferritin and apoferritin (5 min as against 30 min after initiation of a pulse). Time sequence studies of the shifts of biosynthetically labeled subunits and ferritin through different cell compartments provided evidence for vectorial transport of subunits and of ferritin, the direction of transport being from the two polyribosomal systems to the smooth membrane compartment and to the cytosol."}
{"id": "PMID:191451", "title": "Biosynthesis of ferritin in rat hepatoma cells and rat livers. II. Binding of iron by ferritin protein.", "content": "Ferritin and its protein subunits in rat hepatoma cell clone M-5123-C1 were biosynthetically labeled with [14C]leucine and 59Fe. Radioimmunoassays of ferritin/apoferritin and of protein subunits in the free polyribosome, membrane-bound polyribosome, smooth membrane, and cytosol fractions were done with ferritin-specific and subunit-specific rabbit IgG antibodies at various time intervals after pulsing. Much more 59Fe was bound by ferritin/apoferritin than by subunits in all of the cell fractions. Binding of iron to subunits may have been a random process. When hepatoma cells were simultaneously pulse-labeled with 59Fe and [14C]leucine, uptake of much of the 59Fe by ferritin occurred relatively early, in comparison to incorporation of [14C]leucine, in all of the cell fractions examined. Thus, 59Fe was readily incorporated into pre-existing ferritin. We conclude that most, if not nearly all, of the iron is incorporated after assembly of protein subunits.", "contents": "Biosynthesis of ferritin in rat hepatoma cells and rat livers. II. Binding of iron by ferritin protein. Ferritin and its protein subunits in rat hepatoma cell clone M-5123-C1 were biosynthetically labeled with [14C]leucine and 59Fe. Radioimmunoassays of ferritin/apoferritin and of protein subunits in the free polyribosome, membrane-bound polyribosome, smooth membrane, and cytosol fractions were done with ferritin-specific and subunit-specific rabbit IgG antibodies at various time intervals after pulsing. Much more 59Fe was bound by ferritin/apoferritin than by subunits in all of the cell fractions. Binding of iron to subunits may have been a random process. When hepatoma cells were simultaneously pulse-labeled with 59Fe and [14C]leucine, uptake of much of the 59Fe by ferritin occurred relatively early, in comparison to incorporation of [14C]leucine, in all of the cell fractions examined. Thus, 59Fe was readily incorporated into pre-existing ferritin. We conclude that most, if not nearly all, of the iron is incorporated after assembly of protein subunits."}
{"id": "PMID:191452", "title": "Effect of variations in lipopolysaccharide on the fluidity of the outer membrane of Escherichia coli.", "content": "The lipid hydrocarbon chains in the outer membrane of gram-negative bacteria appear from previous experiments to be less mobile than in the cytoplasmic membrane. To determine whether lipopolysaccharide, a unique outer membrane component, is a cause of this restricted mobility, outer membranes differing in the amount of lipopolysaccharide, and the length of the polysaccharide side chain, were prepared from Escherichia coli J5. Cytoplasmic membranes were prepared for comparison. The probes, 5- and 12-doxylstearate, were introduced into these membranes, electron spin resonance spectra were analyzed, and the order parameter (S) and empirical motion parameter (tau0) were calculated. Outer membrane preparations containing long chain lipopolysaccharide were much less fluid by these criteria than were preparations containing short chain lipopolysaccharide. Removing about 40% of the lipopolysaccharide from the former preparations greatly increased their fluidity. The lipid in the cytoplasmic membrane preparations was more fluid than in the outer membrane and cytoplasmic membranes were similar to each other regardless of the composition of the outer membrane. These results indicate that lipopolysaccharide, and especially the polysaccharide portion, directly or indirectly causes the restricted mobility of the lipid hydrocarbon chains observed in the outer membrane.", "contents": "Effect of variations in lipopolysaccharide on the fluidity of the outer membrane of Escherichia coli. The lipid hydrocarbon chains in the outer membrane of gram-negative bacteria appear from previous experiments to be less mobile than in the cytoplasmic membrane. To determine whether lipopolysaccharide, a unique outer membrane component, is a cause of this restricted mobility, outer membranes differing in the amount of lipopolysaccharide, and the length of the polysaccharide side chain, were prepared from Escherichia coli J5. Cytoplasmic membranes were prepared for comparison. The probes, 5- and 12-doxylstearate, were introduced into these membranes, electron spin resonance spectra were analyzed, and the order parameter (S) and empirical motion parameter (tau0) were calculated. Outer membrane preparations containing long chain lipopolysaccharide were much less fluid by these criteria than were preparations containing short chain lipopolysaccharide. Removing about 40% of the lipopolysaccharide from the former preparations greatly increased their fluidity. The lipid in the cytoplasmic membrane preparations was more fluid than in the outer membrane and cytoplasmic membranes were similar to each other regardless of the composition of the outer membrane. These results indicate that lipopolysaccharide, and especially the polysaccharide portion, directly or indirectly causes the restricted mobility of the lipid hydrocarbon chains observed in the outer membrane."}
{"id": "PMID:191453", "title": "Inhibition and inactivation of bovine mammary and liver UDP-galactose-4-epimerases.", "content": "Bovine liver and mammary UDP-galactose-4-epimerases were investigated with respect to various inhibitors and inactivators. Uridine nucleotides and NADH are potent inhibitors with Ki values in the low micromolar range. The NAD+/NADH ratio may be an important physiological control mechanism for it affects markedly the activity of the enzyme with 50% inhibition occurring at a ratio of 20:1. In the presence of uridine nucleotides binding of NADH to the epimerases is enhanced. Consequently, the effect of changes in the NAD+/NADH ratio in vivo would not be immediately apparent as uridine nucleotides would slow down the displacement of NADH by NAD+. Neither uridine nor galactose 1-phosphate inhibits the purified enzymes as previously reported with the impure liver enzyme. Uridine nucleotides provide almost total protection against the apparent first order inactivation of the epimerases by trypsin and allow determination of dissociation constants. NAD+ partially protects against trypsin inactivation. Inactivation with various sulfhydryl reagents is complex and the results indicate that at least three sulfhydryl groups may be modified before total inactivation occurs. Partial inactivation occurs upon modification of the epimerases with 2-hydroxy-5-nitrogenzyl bromide. Some protection against this modification is provided by the combination of NAD+ and UDP.", "contents": "Inhibition and inactivation of bovine mammary and liver UDP-galactose-4-epimerases. Bovine liver and mammary UDP-galactose-4-epimerases were investigated with respect to various inhibitors and inactivators. Uridine nucleotides and NADH are potent inhibitors with Ki values in the low micromolar range. The NAD+/NADH ratio may be an important physiological control mechanism for it affects markedly the activity of the enzyme with 50% inhibition occurring at a ratio of 20:1. In the presence of uridine nucleotides binding of NADH to the epimerases is enhanced. Consequently, the effect of changes in the NAD+/NADH ratio in vivo would not be immediately apparent as uridine nucleotides would slow down the displacement of NADH by NAD+. Neither uridine nor galactose 1-phosphate inhibits the purified enzymes as previously reported with the impure liver enzyme. Uridine nucleotides provide almost total protection against the apparent first order inactivation of the epimerases by trypsin and allow determination of dissociation constants. NAD+ partially protects against trypsin inactivation. Inactivation with various sulfhydryl reagents is complex and the results indicate that at least three sulfhydryl groups may be modified before total inactivation occurs. Partial inactivation occurs upon modification of the epimerases with 2-hydroxy-5-nitrogenzyl bromide. Some protection against this modification is provided by the combination of NAD+ and UDP."}
{"id": "PMID:191454", "title": "Isolation, chemical characterization, and biophysical properties of three different abnormal lipoproteins: LP-X1, LP-X2, and LP-X3.", "content": "Three different but related abnormal lipoprotein species, LP-X1, LP-X2, and LP-X3, have been isolated from cholestatic plasma by ethanol precipitation and zonal ultracentrifugation. All three populations are rich in phospholipids (64.9 to 67.5%) and cholesterol (23.0 to 26.8%) but poor in cholesteryl esters (0.4 to 1.9%), triglycerides (1.8 to 3.2%), and protein (3.2 to 6.7%) with differences in chemical composition which result in buoyant densities (1.038, 1.049, and 1.058, respectively) to allow their separation. LP-X1, LP-X2, and LP-X3 exhibited apparent flotation rates of 17.3, 9.7, and 3.2 Svedbergs and Stokes radii of 339, 343, and 294 A, respectively. As determined from circular dichroic measurements, the protein constituents of all three particles possessed a high degree of alpha helical structure (41 to 65%). Each LP-X particle exhibited abnormally low fluidity as evaluated by electron paramagnetic resonance. All of the particles contained human serum albumin and the C-proteins as major protein constituents, but only LP-X2 and LP-X3 contained apolipoprotein A-I and apolipoprotein E.", "contents": "Isolation, chemical characterization, and biophysical properties of three different abnormal lipoproteins: LP-X1, LP-X2, and LP-X3. Three different but related abnormal lipoprotein species, LP-X1, LP-X2, and LP-X3, have been isolated from cholestatic plasma by ethanol precipitation and zonal ultracentrifugation. All three populations are rich in phospholipids (64.9 to 67.5%) and cholesterol (23.0 to 26.8%) but poor in cholesteryl esters (0.4 to 1.9%), triglycerides (1.8 to 3.2%), and protein (3.2 to 6.7%) with differences in chemical composition which result in buoyant densities (1.038, 1.049, and 1.058, respectively) to allow their separation. LP-X1, LP-X2, and LP-X3 exhibited apparent flotation rates of 17.3, 9.7, and 3.2 Svedbergs and Stokes radii of 339, 343, and 294 A, respectively. As determined from circular dichroic measurements, the protein constituents of all three particles possessed a high degree of alpha helical structure (41 to 65%). Each LP-X particle exhibited abnormally low fluidity as evaluated by electron paramagnetic resonance. All of the particles contained human serum albumin and the C-proteins as major protein constituents, but only LP-X2 and LP-X3 contained apolipoprotein A-I and apolipoprotein E."}
{"id": "PMID:191455", "title": "Interaction of human and bovine A-1 apolipoproteins with L-alpha-dimyristoyl phosphadicylcholine and L-alpha-myristoyl lysophosphatidylcholine.", "content": "The major protein components from human and bovine high density serum lipoproteins (apo-A-I proteins) were investigated in their interactions with L-alpha-myristoyl lysophosphatidylcholine and L-alpha-dimyristoyl phosphatidylcholine. Complex formation was followed by 25 degrees by observing changes in fluorescence polarization, rotational relaxation times (ph), and CD spectra of the proteins, covalently labeled with fluorescent dimethylaminonaphthalene sulfonyl groups. Monomeric human apo-A-I and initially oligomeric bovine apo-A-I interact with similar efficiency with the same amphiphiles. During binding of L-alpha-myristoyl lysophosphatidylcholine and L-alpha-dimyristoyl phosphatidylcholine, the structure of both proteins changes drastically, exhibiting about 35% increases in secondary structure with the phospholipid and about 20% increases with the lysophospholipid. Simultaneously, regions of the proteins adjacent to the fluorescent probes become more mobile. With the bovine protein, binding of both amphiphiles results in changes in the oligomeric structure: dissociation with L-alpha-myristoyl lysophosphatidylcholine and dissociation or rearrangement with L-alpha-dimyristoyl phosphatidylcholine. The complexes formed in the presence of excess L-alpha-myristoyl lysophosphatidylcholine are flexible structures with considerable rotational freedom. The largest rotational unit in these complexes has ph = 60 ns for both proteins; by comparison, the monometic human apo-A-I has a ph = 73.5 ns. Interactions of both proteins with the lysophospholipid take place well above its critical micelle concentration, but probably involve binding of monomeric lipid. With L-alpha-dimyristoyl phosphatidylcholine the complexes are different from those formed with the lysophospholipid. They have limiting ph values of 250 +/- 50 and 280 +/- 60 ns with the human and bovine proteins, respectively. These ph values are consistent with particles of the general size of human high density lipoprotein rather than of liposomes and indicate the formation of distinct, relatively small structures upon interaction of the self-associated lipid with the apo-A-I-proteins.", "contents": "Interaction of human and bovine A-1 apolipoproteins with L-alpha-dimyristoyl phosphadicylcholine and L-alpha-myristoyl lysophosphatidylcholine. The major protein components from human and bovine high density serum lipoproteins (apo-A-I proteins) were investigated in their interactions with L-alpha-myristoyl lysophosphatidylcholine and L-alpha-dimyristoyl phosphatidylcholine. Complex formation was followed by 25 degrees by observing changes in fluorescence polarization, rotational relaxation times (ph), and CD spectra of the proteins, covalently labeled with fluorescent dimethylaminonaphthalene sulfonyl groups. Monomeric human apo-A-I and initially oligomeric bovine apo-A-I interact with similar efficiency with the same amphiphiles. During binding of L-alpha-myristoyl lysophosphatidylcholine and L-alpha-dimyristoyl phosphatidylcholine, the structure of both proteins changes drastically, exhibiting about 35% increases in secondary structure with the phospholipid and about 20% increases with the lysophospholipid. Simultaneously, regions of the proteins adjacent to the fluorescent probes become more mobile. With the bovine protein, binding of both amphiphiles results in changes in the oligomeric structure: dissociation with L-alpha-myristoyl lysophosphatidylcholine and dissociation or rearrangement with L-alpha-dimyristoyl phosphatidylcholine. The complexes formed in the presence of excess L-alpha-myristoyl lysophosphatidylcholine are flexible structures with considerable rotational freedom. The largest rotational unit in these complexes has ph = 60 ns for both proteins; by comparison, the monometic human apo-A-I has a ph = 73.5 ns. Interactions of both proteins with the lysophospholipid take place well above its critical micelle concentration, but probably involve binding of monomeric lipid. With L-alpha-dimyristoyl phosphatidylcholine the complexes are different from those formed with the lysophospholipid. They have limiting ph values of 250 +/- 50 and 280 +/- 60 ns with the human and bovine proteins, respectively. These ph values are consistent with particles of the general size of human high density lipoprotein rather than of liposomes and indicate the formation of distinct, relatively small structures upon interaction of the self-associated lipid with the apo-A-I-proteins."}
{"id": "PMID:191456", "title": "Physical properties of isolated complexes of human and bovine A-I apolipoproteins with L-alpha-dimyristoyl phosphatidylcholine.", "content": "Human or bovine A-I apolipoproteins in solution form complexes with sonicated L-alpha-dimirystoyl phosphatidylcholine at 23 and 37 degrees, but not at 8 degrees, suggesting a strong dependence of the interaction on the physical state of the lipid (phase transition temperature 23 degrees). Complexes were isolated by gel filtration on a Sepharose 4B column and were subsequently analyzed for protein and lipid content, molecular weight, and physical state of the lipid portion. The average stoichiometry of all complexes, regardless of the initial concentrations or ratios of protein and lipid, was constant: 90 +/- 20 mol of phospholipid/mol of protein monomer, suggesting a highly cooperative interaction. Sedimentation equilibrium experiments indicated homogeneous macromolecular preparations and gave molecular weights around 235,000 (+/- 15%) for the complexes, with the human and bovine apo-A-I proteins contributing 77,000 (+/- 10%), i.e. about three protein subunits per complex. The lipid portion of the complexes retained some characteristics of a bilayer: it had a broad phase transition with a midpoint at 25.5 degrees as reported by the fluorescence polarization of the lipophilic probe diphenylhexatriene. Above the phase transition temperature the mobility of the phospholipids in the complexes with both apo-A-I proteins was considerably decreased relative to the pure L-alpha-dimyristoyl phosphatidylcholine dispersion; below the phase transition temperature the opposite was true, i.e. the protein fluidized the lipids. The results indicate that apol-A-I proteins interact stoichiometrically with L-alpha-dimyristoyl phosphatidylcholine vesicles above the gel to liquid-crystalline transition temperature of the lipid, promoting the destruction of vesicles and the formation of well defined particles of the general size of high density serum lipoproteins.", "contents": "Physical properties of isolated complexes of human and bovine A-I apolipoproteins with L-alpha-dimyristoyl phosphatidylcholine. Human or bovine A-I apolipoproteins in solution form complexes with sonicated L-alpha-dimirystoyl phosphatidylcholine at 23 and 37 degrees, but not at 8 degrees, suggesting a strong dependence of the interaction on the physical state of the lipid (phase transition temperature 23 degrees). Complexes were isolated by gel filtration on a Sepharose 4B column and were subsequently analyzed for protein and lipid content, molecular weight, and physical state of the lipid portion. The average stoichiometry of all complexes, regardless of the initial concentrations or ratios of protein and lipid, was constant: 90 +/- 20 mol of phospholipid/mol of protein monomer, suggesting a highly cooperative interaction. Sedimentation equilibrium experiments indicated homogeneous macromolecular preparations and gave molecular weights around 235,000 (+/- 15%) for the complexes, with the human and bovine apo-A-I proteins contributing 77,000 (+/- 10%), i.e. about three protein subunits per complex. The lipid portion of the complexes retained some characteristics of a bilayer: it had a broad phase transition with a midpoint at 25.5 degrees as reported by the fluorescence polarization of the lipophilic probe diphenylhexatriene. Above the phase transition temperature the mobility of the phospholipids in the complexes with both apo-A-I proteins was considerably decreased relative to the pure L-alpha-dimyristoyl phosphatidylcholine dispersion; below the phase transition temperature the opposite was true, i.e. the protein fluidized the lipids. The results indicate that apol-A-I proteins interact stoichiometrically with L-alpha-dimyristoyl phosphatidylcholine vesicles above the gel to liquid-crystalline transition temperature of the lipid, promoting the destruction of vesicles and the formation of well defined particles of the general size of high density serum lipoproteins."}
{"id": "PMID:191457", "title": "Direct assignment of the cysteinyl, the slowly exchangeable, and the aromatic ring 1H nuclear magnetic resonances in clostridial-type ferredoxins.", "content": "We have directly assigned the 1H NMR corresponding to the cysteinyl protons, the slowly exchangeable protons, and the aromatic ring protons in the 1H NMR spectrum of Clostridium acidi-urici ferredoxin by isotopic labeling and 13C NMR decoupling techniques. We also show that the resonance pattern in the 8- to 20-ppm (from 2,2-dimethyl-2-sialapentanesulfonic acid) region of the 1H NMR spectra of oxidized Clostridium acidi-urici, Clostridium pasteurianum, Clostridium perfringens, and Peptococcus aerogenes ferredoxins are very similar, and we assign the resonances in this region by analogy with the spectrum of C. acidi-urici ferredoxin. The 1H NMR spectra of the beta protons of the cysteinyl residues of these ferredoxins differ, however, from the 1H NMR spectra of equivalent beta protons of the methylene carbon atoms bonded via a sulfur atom to [4Fe-4S] clusters in synthetic inorganic analogues. In the spectra of the synthetic compounds, the beta protons appear as a single resonance shifted 10 ppm from its unbonded reference position. In the spectra of oxidized clostridial ferredoxins, the cysteinyl beta protons appear as a series of at least eight resolved resonances with shifts that range from 6 to 14 ppm, relative to the free amino acid resonance position. This difference in the spectra of the protein and the synthetic compounds probably results from the fact that the equivalent beta protons of the synthetic compounds are not constrained and are free to rotate and thus assume the same average orientation with respect to the [4Fe-4S] cluster. The shift pattern in the 9- to 14-ppm region is identical in three different clostridial ferredoxins. This suggests that the molecular environments of the corresponding cysteinyl residues are identical. Significant differences in the resonance positions occur, however, in the 14- to 18-ppm region, suggesting that the physical environments of these cysteinyl residues differ. This may reflect differences in the orientation of the corresponding cysteinyl residues relative to the [4Fe-4S] clusters or differences in charge density at the cysteinyl beta protons or both. The slowly exchangeable protons were identified by comparing the 1H NMR spectra of ferredoxins reconstituted in H2O and 2H2O. The remaining resonances in the 8- to 20-ppm region were assigned to each of the 2 tyrosyl residues in C. acidi-urici ferredoxin. This was done by comparing the 1H NMR spectra of C. acidi-urici [(3',5'-2H2)Tyr]ferredoxin and C. acidi-urici [PHE2]ferredoxin with that of C. acidi-urici native ferredoxin.", "contents": "Direct assignment of the cysteinyl, the slowly exchangeable, and the aromatic ring 1H nuclear magnetic resonances in clostridial-type ferredoxins. We have directly assigned the 1H NMR corresponding to the cysteinyl protons, the slowly exchangeable protons, and the aromatic ring protons in the 1H NMR spectrum of Clostridium acidi-urici ferredoxin by isotopic labeling and 13C NMR decoupling techniques. We also show that the resonance pattern in the 8- to 20-ppm (from 2,2-dimethyl-2-sialapentanesulfonic acid) region of the 1H NMR spectra of oxidized Clostridium acidi-urici, Clostridium pasteurianum, Clostridium perfringens, and Peptococcus aerogenes ferredoxins are very similar, and we assign the resonances in this region by analogy with the spectrum of C. acidi-urici ferredoxin. The 1H NMR spectra of the beta protons of the cysteinyl residues of these ferredoxins differ, however, from the 1H NMR spectra of equivalent beta protons of the methylene carbon atoms bonded via a sulfur atom to [4Fe-4S] clusters in synthetic inorganic analogues. In the spectra of the synthetic compounds, the beta protons appear as a single resonance shifted 10 ppm from its unbonded reference position. In the spectra of oxidized clostridial ferredoxins, the cysteinyl beta protons appear as a series of at least eight resolved resonances with shifts that range from 6 to 14 ppm, relative to the free amino acid resonance position. This difference in the spectra of the protein and the synthetic compounds probably results from the fact that the equivalent beta protons of the synthetic compounds are not constrained and are free to rotate and thus assume the same average orientation with respect to the [4Fe-4S] cluster. The shift pattern in the 9- to 14-ppm region is identical in three different clostridial ferredoxins. This suggests that the molecular environments of the corresponding cysteinyl residues are identical. Significant differences in the resonance positions occur, however, in the 14- to 18-ppm region, suggesting that the physical environments of these cysteinyl residues differ. This may reflect differences in the orientation of the corresponding cysteinyl residues relative to the [4Fe-4S] clusters or differences in charge density at the cysteinyl beta protons or both. The slowly exchangeable protons were identified by comparing the 1H NMR spectra of ferredoxins reconstituted in H2O and 2H2O. The remaining resonances in the 8- to 20-ppm region were assigned to each of the 2 tyrosyl residues in C. acidi-urici ferredoxin. This was done by comparing the 1H NMR spectra of C. acidi-urici [(3',5'-2H2)Tyr]ferredoxin and C. acidi-urici [PHE2]ferredoxin with that of C. acidi-urici native ferredoxin."}
{"id": "PMID:191458", "title": "Initiation of synthesis of messenger RNA of deoxynucleotide kinase by oligoribonucleotides.", "content": "The effects of nucleoside triphosphates and oligoribonucleotides on the initiation of synthesis of messenger RNA of the T4 phage-specific enzyme, deoxynucleotide kinase, have been studied. The procedure involved incubation of T4 DNA, purified RNA polymerase from Escherichia coli, and selected nucleotide compounds during a brief period to permit initiation of RNA synthesis. Further initiation was arrested by the addition of ribampicin, and completion of the transcription of the newly initiated RNA was permitted to take place in the presence of the full complement of nucleoside triphosphates. After translation of the messenger RNA into phage-specific enzymes, the measured activities of the latter whe first incubation period. The effectiveness of individual nucleoside triphosphates, when present singly or in combination during the initiation period, was compared to that when all four nucleoside triphosphates were available. ATP alone was extremely effective as an initiator of the synthesis of the messenger RNA for deoxynucleotide kinase. The addition of UTP to ATP not only enhanced the magnitude of initiation but also affected the kinetics of ATP interaction with T4 DNA and RNA polymerase during the initiation period. Several oligoribonucleotides including a series ApA to ApApApA, UpU to UpUpUpU, and the heteropolymers, Ap1pU and ApApApU, were tested as initiators of kinase mRNA synthesis. A sequence of nucleotides in the promoter region of T4 DNA for the deoxynucleotide kinase gene has been proposed as a result of these experiments.", "contents": "Initiation of synthesis of messenger RNA of deoxynucleotide kinase by oligoribonucleotides. The effects of nucleoside triphosphates and oligoribonucleotides on the initiation of synthesis of messenger RNA of the T4 phage-specific enzyme, deoxynucleotide kinase, have been studied. The procedure involved incubation of T4 DNA, purified RNA polymerase from Escherichia coli, and selected nucleotide compounds during a brief period to permit initiation of RNA synthesis. Further initiation was arrested by the addition of ribampicin, and completion of the transcription of the newly initiated RNA was permitted to take place in the presence of the full complement of nucleoside triphosphates. After translation of the messenger RNA into phage-specific enzymes, the measured activities of the latter whe first incubation period. The effectiveness of individual nucleoside triphosphates, when present singly or in combination during the initiation period, was compared to that when all four nucleoside triphosphates were available. ATP alone was extremely effective as an initiator of the synthesis of the messenger RNA for deoxynucleotide kinase. The addition of UTP to ATP not only enhanced the magnitude of initiation but also affected the kinetics of ATP interaction with T4 DNA and RNA polymerase during the initiation period. Several oligoribonucleotides including a series ApA to ApApApA, UpU to UpUpUpU, and the heteropolymers, Ap1pU and ApApApU, were tested as initiators of kinase mRNA synthesis. A sequence of nucleotides in the promoter region of T4 DNA for the deoxynucleotide kinase gene has been proposed as a result of these experiments."}
{"id": "PMID:191459", "title": "Glycogen synthase kinases. Distribution in mammalian tissues of forms that are independent of cyclic AMP.", "content": "Extracts of rat tissues contain kinases which catalyze the conversion of glycogen synthease from the glucose 6-phosphate-independent (I) form to the glucose 6-phosphatate-dependent (D) form. These kinases were stimulated by adenosine 3':5' monophosphate (cyclic AMP). The glycogen synthase kinase activity ratio (activity in the absence of cyclic AMP divided by activity in the presence of cyclic AMP) varied from 0.28 to 0.97. The activity ratio for histone kinase in the same extracts ranged from 0.11 to 0.29. The levels of glycogen synthase kinase varied by a factor of 80 in the following rat tissues (given in order of decreasing enzyme activity): kidney, liver, stomach mucosa, lung, brain, heart, skeletal muscle, and adipose tissue. In the same tissues the levels of histone kinase varied by only a factor of 6 and did not correlate with the levels of glycogen synthase kinase. A modification of the method of Walsh et al. ((1971) J. Biol. Chem. 246, 1977-1985) was developed for purification of the heat-stable inhibitor of cyclic AMP-dependent protein kinases (inhibitor). The modified procedure resulted in good yields of highly purified inhibitor and was much simpler than the previously described procedure. This inhibitor completely inhibited cyclic AMP-dependent histone kinase activity of the extracts but much of the glycogen synthase kinase activity was not inhibited. The portion of glycogen synthase kinase that was insensitive to the inhibitor was: stomach mucosa, 95%; brain, 90%; liver, 82%; kidney, 81%; lung, 68%; adipose tissue, 65%; skeletal muscle, 63%; and heart, 54%. This histone kinase activity in the extracts and hte ratio of glycogen synthase kinase to histone kinase activity of purified catalytic subunit of the cyclic AMP-dependent protein kinase was used to calculate for each extract the glycogen synthase kinase activity contributed by the cyclic AMP-dependent protein kinase. Based on these calculations, the portion of the glycogen synthase kinase which was due to kinases independent of cyclic AMP was: kidney, 97%; liver, 91%; lung, 89%; brain, 87%, heart, 85%; stomach mucosa, 84%; adipose tissue, 38%; and skeletal muscle, 33%. A significant portion of the glycogen synthase kinase activity, but virtually none of the cyclic AMP-dependent histone kinase activity, of these extracts could be adsorbed to phosphocellulose columns. Liver extracts contained, in addition, a form of glycogen synthase kinase which was not adsorbed to phosphocellulose and which could be separated from the cyclic AMP-dependent protein kinase by additional chromatography. These studies demonstrate that kinases independent of cyclic AMP account for most of the glycogen synthase kinase activity of many tissues. The widespread distribution and high concentrations of these enzymes suggest that they are of physiological importance.", "contents": "Glycogen synthase kinases. Distribution in mammalian tissues of forms that are independent of cyclic AMP. Extracts of rat tissues contain kinases which catalyze the conversion of glycogen synthease from the glucose 6-phosphate-independent (I) form to the glucose 6-phosphatate-dependent (D) form. These kinases were stimulated by adenosine 3':5' monophosphate (cyclic AMP). The glycogen synthase kinase activity ratio (activity in the absence of cyclic AMP divided by activity in the presence of cyclic AMP) varied from 0.28 to 0.97. The activity ratio for histone kinase in the same extracts ranged from 0.11 to 0.29. The levels of glycogen synthase kinase varied by a factor of 80 in the following rat tissues (given in order of decreasing enzyme activity): kidney, liver, stomach mucosa, lung, brain, heart, skeletal muscle, and adipose tissue. In the same tissues the levels of histone kinase varied by only a factor of 6 and did not correlate with the levels of glycogen synthase kinase. A modification of the method of Walsh et al. ((1971) J. Biol. Chem. 246, 1977-1985) was developed for purification of the heat-stable inhibitor of cyclic AMP-dependent protein kinases (inhibitor). The modified procedure resulted in good yields of highly purified inhibitor and was much simpler than the previously described procedure. This inhibitor completely inhibited cyclic AMP-dependent histone kinase activity of the extracts but much of the glycogen synthase kinase activity was not inhibited. The portion of glycogen synthase kinase that was insensitive to the inhibitor was: stomach mucosa, 95%; brain, 90%; liver, 82%; kidney, 81%; lung, 68%; adipose tissue, 65%; skeletal muscle, 63%; and heart, 54%. This histone kinase activity in the extracts and hte ratio of glycogen synthase kinase to histone kinase activity of purified catalytic subunit of the cyclic AMP-dependent protein kinase was used to calculate for each extract the glycogen synthase kinase activity contributed by the cyclic AMP-dependent protein kinase. Based on these calculations, the portion of the glycogen synthase kinase which was due to kinases independent of cyclic AMP was: kidney, 97%; liver, 91%; lung, 89%; brain, 87%, heart, 85%; stomach mucosa, 84%; adipose tissue, 38%; and skeletal muscle, 33%. A significant portion of the glycogen synthase kinase activity, but virtually none of the cyclic AMP-dependent histone kinase activity, of these extracts could be adsorbed to phosphocellulose columns. Liver extracts contained, in addition, a form of glycogen synthase kinase which was not adsorbed to phosphocellulose and which could be separated from the cyclic AMP-dependent protein kinase by additional chromatography. These studies demonstrate that kinases independent of cyclic AMP account for most of the glycogen synthase kinase activity of many tissues. The widespread distribution and high concentrations of these enzymes suggest that they are of physiological importance."}
{"id": "PMID:191460", "title": "Biological cross-reactivity of rat testis phosphodiesterase activator protein and rabbit skeletal muscle troponin-C.", "content": "Phosphodiesterase activator protein and troponin-C have been purified from rat testis and rabbit skeletal muscle, respectively. The two proteins appear to be structurally distinct since the activator protein migrates faster than troponin-C on sodium dodecyl sulfate-polyacrylamide gels. Each of the calcium-binding proteins will, however, substitute for the other in their respective biological systems. Testis activator protein forms a complex with rabbit muscle troponin subunits TnI and TnT soluble in low salt. This hybrid complex (AIT) can regulate rabbit skeletal muscle actomyosin ATPase activity. AIT regulation, although influenced by free Aa2+ levels, is distinct from that of native troponin. Likewise, muscle troponin-C can substitute for activator protein in the stimulation of cyclic nucleotide phosphodiesterase. Troponin-C will fully stimulate phosphodiesterase although its affinity is 600-fold lower than that of activator protein. Ca2+ regulation studies demonstrate that both proteins require micormolar levels of free Ca2+ to induce phosphodiesterase activation. Activator protein requires 1.2 x 10(6) M and troponin-C, 1.9 X 10(6) M free Ca2+ for half-maximal stimulation of phosphodiesterase. The biological cross-reactivity of these proteins supports the sequence homology recently reported by Watterson et al. (Watterson, D.M., Harrelson, W.G., Keller, P.M., Sharief, F., and Vanaman, T.C. (1976) J.Biol. Chem. 251, 4501-4513). In addition, this preliminary study suggests that this nonmuscle troponin-C-like protein potentially may function in other Ca2+-regulated cellular events in addition to its moculation of cyclic nucleotide levels.", "contents": "Biological cross-reactivity of rat testis phosphodiesterase activator protein and rabbit skeletal muscle troponin-C. Phosphodiesterase activator protein and troponin-C have been purified from rat testis and rabbit skeletal muscle, respectively. The two proteins appear to be structurally distinct since the activator protein migrates faster than troponin-C on sodium dodecyl sulfate-polyacrylamide gels. Each of the calcium-binding proteins will, however, substitute for the other in their respective biological systems. Testis activator protein forms a complex with rabbit muscle troponin subunits TnI and TnT soluble in low salt. This hybrid complex (AIT) can regulate rabbit skeletal muscle actomyosin ATPase activity. AIT regulation, although influenced by free Aa2+ levels, is distinct from that of native troponin. Likewise, muscle troponin-C can substitute for activator protein in the stimulation of cyclic nucleotide phosphodiesterase. Troponin-C will fully stimulate phosphodiesterase although its affinity is 600-fold lower than that of activator protein. Ca2+ regulation studies demonstrate that both proteins require micormolar levels of free Ca2+ to induce phosphodiesterase activation. Activator protein requires 1.2 x 10(6) M and troponin-C, 1.9 X 10(6) M free Ca2+ for half-maximal stimulation of phosphodiesterase. The biological cross-reactivity of these proteins supports the sequence homology recently reported by Watterson et al. (Watterson, D.M., Harrelson, W.G., Keller, P.M., Sharief, F., and Vanaman, T.C. (1976) J.Biol. Chem. 251, 4501-4513). In addition, this preliminary study suggests that this nonmuscle troponin-C-like protein potentially may function in other Ca2+-regulated cellular events in addition to its moculation of cyclic nucleotide levels."}
{"id": "PMID:191461", "title": "Preferential usage of glycyl-tRNA isoaccepting species in collagen synthesis.", "content": "Chick embryo tRNA charged with [3H]glycine was incubated in an in vitro protein-synthesizing system using polysomes isolated from either chick embryo liver or calvaria. Using collagenase digestion to measure the fraction of protein synthesized which was collagenous, the results indicate that in the calvaria system approximately 65% of the incorporated [3H]glycine was in collagen. The incorporation of [3H]glycine into protein from individual isoaccepting species was determined by chromatography on a reversed phase system of the charged tRNA before and after incubation in the polysome systems. In the calvaria system, a single tRNAGly species cognate to GGU and GGC and which is found in unusually large amounts in collagen-synthesizing tissues was used preferentially in collagen-synthesizing tissues was used preferentially in collagen synthesis. In the liver system, the rate of incorporation was similar to the calvaria, but no collagen synthesis was detected and only a relatively small preferential usage of any of the four major isoaccepting species was observed. These results support the notion that the complement of tRNA found in a cell may be adapted to the synthesis of a particular protein. It is also possible that under certain circumstances, collagen synthesis may be controlled in vivo at the translational level by the concentration of particular tRNA species.", "contents": "Preferential usage of glycyl-tRNA isoaccepting species in collagen synthesis. Chick embryo tRNA charged with [3H]glycine was incubated in an in vitro protein-synthesizing system using polysomes isolated from either chick embryo liver or calvaria. Using collagenase digestion to measure the fraction of protein synthesized which was collagenous, the results indicate that in the calvaria system approximately 65% of the incorporated [3H]glycine was in collagen. The incorporation of [3H]glycine into protein from individual isoaccepting species was determined by chromatography on a reversed phase system of the charged tRNA before and after incubation in the polysome systems. In the calvaria system, a single tRNAGly species cognate to GGU and GGC and which is found in unusually large amounts in collagen-synthesizing tissues was used preferentially in collagen-synthesizing tissues was used preferentially in collagen synthesis. In the liver system, the rate of incorporation was similar to the calvaria, but no collagen synthesis was detected and only a relatively small preferential usage of any of the four major isoaccepting species was observed. These results support the notion that the complement of tRNA found in a cell may be adapted to the synthesis of a particular protein. It is also possible that under certain circumstances, collagen synthesis may be controlled in vivo at the translational level by the concentration of particular tRNA species."}
{"id": "PMID:191462", "title": "Resection-arthrodesis for malignant and potentially malignant lesions about the knee using an intramedullary rod and local bone grafts.", "content": "Twenty patients with malignant or potentially malignant tumors (osteogenic sarcoma, giant-cell tumor, synovial-cell sarcoma, chondrosarcoma, and chondroblastoma) located in the proximal end of the tibia or distal end of the femur were treated by local resection and arthrodesis employing an intramedullary rod and autogenous segmental cortical grafts obtained from the same extremity. Use of a customized bent, fluted rod in the most recent cases provided more stable fixation. There was only one local recurrence. In properly selected patients, the method provided a stable extremity that permitted resumption of a vigorous life-style within approximately one year.", "contents": "Resection-arthrodesis for malignant and potentially malignant lesions about the knee using an intramedullary rod and local bone grafts. Twenty patients with malignant or potentially malignant tumors (osteogenic sarcoma, giant-cell tumor, synovial-cell sarcoma, chondrosarcoma, and chondroblastoma) located in the proximal end of the tibia or distal end of the femur were treated by local resection and arthrodesis employing an intramedullary rod and autogenous segmental cortical grafts obtained from the same extremity. Use of a customized bent, fluted rod in the most recent cases provided more stable fixation. There was only one local recurrence. In properly selected patients, the method provided a stable extremity that permitted resumption of a vigorous life-style within approximately one year."}
{"id": "PMID:191463", "title": "Experimental sensory reinnervation of the median nerve by nerve transfer in monkeys.", "content": "Anastomosis of the superficial radial nerve, the dorsal cutaneous branch of the ulnar nerve, or both to the distal cut end of a widely resected median nerve in monkeys was followed by successful sensory reinnervation of the thumb, index finger, and long finger within thiry-five to forty weeks. Success was ascertained by the presence of an intact anastomosis as observed grossly without any evidence of spontaneous regeneration of the median nerve. Reinnervation was confirmed by histological and histochemical reactions observed in the Meissner's corpuscles in the skin innervated by the median nerve. The demonstration of nerve fiber and the presence of normal specific and non-specific cholinesterase reactions exhibited by the Meissner's corpuscles in the cholinesterase preparations were considered the histological criteria for successful reinnervation. These histological and histochemical observations may explain the reported functional sensory recovery in clinical cases when similar nerve transfers were done.", "contents": "Experimental sensory reinnervation of the median nerve by nerve transfer in monkeys. Anastomosis of the superficial radial nerve, the dorsal cutaneous branch of the ulnar nerve, or both to the distal cut end of a widely resected median nerve in monkeys was followed by successful sensory reinnervation of the thumb, index finger, and long finger within thiry-five to forty weeks. Success was ascertained by the presence of an intact anastomosis as observed grossly without any evidence of spontaneous regeneration of the median nerve. Reinnervation was confirmed by histological and histochemical reactions observed in the Meissner's corpuscles in the skin innervated by the median nerve. The demonstration of nerve fiber and the presence of normal specific and non-specific cholinesterase reactions exhibited by the Meissner's corpuscles in the cholinesterase preparations were considered the histological criteria for successful reinnervation. These histological and histochemical observations may explain the reported functional sensory recovery in clinical cases when similar nerve transfers were done."}
{"id": "PMID:191466", "title": "A radioimmunoassay for 3,3',5'-L-triiodothyronine (reverse T3): assessment of thyroid gland content and serum measurements in conditions of normal and altered thyroidal economy and following administration of thyrotropin releasing hormone (TRH) and thyrotropin (TSH).", "content": "The present report describes the development of a radioimmunoassay for 3,3',5'-L-triiodothyronine (reverse T3) which is performed on unextracted serum. Utilizing this radioimmunoassay, 21 normal subjects had a mean (+/-SD) serum reverse T3 level of 60 +/- 12 ng/100 ml, 17 of 19 hyperthyroid patients had elevated serum reverse T3 levels, and 10 of 11 hypothyroid subjects had decreased serum reverse T3 concentrations. Thyroidal secretion of reverse T3 was assessed by measurements in samples obtained from the internal carotid artery and jugular vein of sheep following the administration of thyrotropin releasing hormone (TRH) or bovine thyrotropin (TSH). Reverse T3 levels were increased 45-60 min after TRH administration, but TSH administration produced inconsistent alterations in reverse T3, although 18 of 27 samples obtained after TSH injection were higher than their average respective baseline concentration and the mean peak reverse T3 level was 14% higher than baseline. Following TRH administration to 10 normal human subjects, mean serum reverse T3 levels significantly increased from 53.6 ng/100 ml to 56.3ng/100 ml (P less than .05). The thyroid gland content of reverse T3 in human autopsy material was 6.5 +/- 1.5 microng/g tissue. Both pregnancy and estrogen administration were associated with increases in serum reverse T3 concentrations presumably because of their ability to augment thyroxine binding globulin synthesis.", "contents": "A radioimmunoassay for 3,3',5'-L-triiodothyronine (reverse T3): assessment of thyroid gland content and serum measurements in conditions of normal and altered thyroidal economy and following administration of thyrotropin releasing hormone (TRH) and thyrotropin (TSH). The present report describes the development of a radioimmunoassay for 3,3',5'-L-triiodothyronine (reverse T3) which is performed on unextracted serum. Utilizing this radioimmunoassay, 21 normal subjects had a mean (+/-SD) serum reverse T3 level of 60 +/- 12 ng/100 ml, 17 of 19 hyperthyroid patients had elevated serum reverse T3 levels, and 10 of 11 hypothyroid subjects had decreased serum reverse T3 concentrations. Thyroidal secretion of reverse T3 was assessed by measurements in samples obtained from the internal carotid artery and jugular vein of sheep following the administration of thyrotropin releasing hormone (TRH) or bovine thyrotropin (TSH). Reverse T3 levels were increased 45-60 min after TRH administration, but TSH administration produced inconsistent alterations in reverse T3, although 18 of 27 samples obtained after TSH injection were higher than their average respective baseline concentration and the mean peak reverse T3 level was 14% higher than baseline. Following TRH administration to 10 normal human subjects, mean serum reverse T3 levels significantly increased from 53.6 ng/100 ml to 56.3ng/100 ml (P less than .05). The thyroid gland content of reverse T3 in human autopsy material was 6.5 +/- 1.5 microng/g tissue. Both pregnancy and estrogen administration were associated with increases in serum reverse T3 concentrations presumably because of their ability to augment thyroxine binding globulin synthesis."}
{"id": "PMID:191467", "title": "Circadian rhythms in the urinary excretion of cyclic 3',5'-adenosine monophosphate (cyclic AMP) and cyclic 3',5'-guanosine monophosphate (cyclic GMP) in human subjects.", "content": "Significant circadian rhythns in urinary excretion of cyclic AMP, cyclic GMP, creatinine, 17-hydroxycorticosteroids and inorganic phosphorus were demonstrated in three normal subjects (two males and one post-menopausal female) who collected serial 4-h specimens for periods of 33, 22, and 14 days, respectively. Peak excretion of the above substances occurred, respectively, at approximately 1500-1700, 2300-0200, 1700-1800, 1100-1300, and 1800-2200 h. The estimated amplitudes of the rhythms expressed as a percentage of the mean 4-h excretion rate were 12-13%, 9-13%, 9-15%, 30-78% and 22-26%, respectively. With the possible exception of cyclic GMP, all of the observed rhythms appeared to be sinusoidal, with normal periods of 24 h. The rhythms in both cyclic AMP and creatinine excretion, but not in the remaining substances may be explained largely in terms of the known rhythm in glomerular filtration rate. The factors responsible for the rhythm in cyclic GMP excretion are unknown.", "contents": "Circadian rhythms in the urinary excretion of cyclic 3',5'-adenosine monophosphate (cyclic AMP) and cyclic 3',5'-guanosine monophosphate (cyclic GMP) in human subjects. Significant circadian rhythns in urinary excretion of cyclic AMP, cyclic GMP, creatinine, 17-hydroxycorticosteroids and inorganic phosphorus were demonstrated in three normal subjects (two males and one post-menopausal female) who collected serial 4-h specimens for periods of 33, 22, and 14 days, respectively. Peak excretion of the above substances occurred, respectively, at approximately 1500-1700, 2300-0200, 1700-1800, 1100-1300, and 1800-2200 h. The estimated amplitudes of the rhythms expressed as a percentage of the mean 4-h excretion rate were 12-13%, 9-13%, 9-15%, 30-78% and 22-26%, respectively. With the possible exception of cyclic GMP, all of the observed rhythms appeared to be sinusoidal, with normal periods of 24 h. The rhythms in both cyclic AMP and creatinine excretion, but not in the remaining substances may be explained largely in terms of the known rhythm in glomerular filtration rate. The factors responsible for the rhythm in cyclic GMP excretion are unknown."}
{"id": "PMID:191468", "title": "Demonstration of dual rhinovirus infection in humans by isolation of different serotypes in human heteroploid (HeLa) and human diploid fibroblast cell cultures.", "content": "The ability to isolate rhinoviruses in human heteroploid cell cultures was investigated by inoculating HeLa cells (HeLa M) with specimens previously shown to be positive in human diploid cell cultures. The 135 positive specimens selected were representative of 22 different rhinovirus types, and 4 to 9 specimens were available for each serotype. Specimens were inoculated into human diploid fetal tonsil fibroblasts (FT), HeLa cells with 30 mM Mg2+, and HeLa cells without increased Mg2+. One hundred twelve rhinovirus strains (83%) were reisolated in FT cells, whereas 76 rhinovirus strains (56%) were recovered in HeLa cells with 30 mM Mg2+. All strains recovered in FT were the same serotype as that originally recovered in diploid cells, but five of the HeLa cell isolates (3.7% of total specimens) were different serotypes, indicating dual rhinovirus infections. Four rhinovirus serotypes, (3, 42, 48, and 70) were recovered in HeLa but not in diploid cells; these serotypes were rare in our previous studies. Isolation of rhinovirus in FT cells was usually accomplished at first passage, whereas rhinovirus cytopathic effects in HeLa cells were not observed at first passage, but required one, two, or (rarely) three blind passages. Only 28 rhinoviruses (21%) were recovered in HeLa cells without increased Mg2+; however, three serotypes, types 16, 36, and 58, were recovered as effectively in HeLa cells, with or without added Mg2+, as they were in FT cells. In general, rhinoviruses were less efficiently recovered in HeLa cells; however, certain serotypes may be detected better by HeLa cells.", "contents": "Demonstration of dual rhinovirus infection in humans by isolation of different serotypes in human heteroploid (HeLa) and human diploid fibroblast cell cultures. The ability to isolate rhinoviruses in human heteroploid cell cultures was investigated by inoculating HeLa cells (HeLa M) with specimens previously shown to be positive in human diploid cell cultures. The 135 positive specimens selected were representative of 22 different rhinovirus types, and 4 to 9 specimens were available for each serotype. Specimens were inoculated into human diploid fetal tonsil fibroblasts (FT), HeLa cells with 30 mM Mg2+, and HeLa cells without increased Mg2+. One hundred twelve rhinovirus strains (83%) were reisolated in FT cells, whereas 76 rhinovirus strains (56%) were recovered in HeLa cells with 30 mM Mg2+. All strains recovered in FT were the same serotype as that originally recovered in diploid cells, but five of the HeLa cell isolates (3.7% of total specimens) were different serotypes, indicating dual rhinovirus infections. Four rhinovirus serotypes, (3, 42, 48, and 70) were recovered in HeLa but not in diploid cells; these serotypes were rare in our previous studies. Isolation of rhinovirus in FT cells was usually accomplished at first passage, whereas rhinovirus cytopathic effects in HeLa cells were not observed at first passage, but required one, two, or (rarely) three blind passages. Only 28 rhinoviruses (21%) were recovered in HeLa cells without increased Mg2+; however, three serotypes, types 16, 36, and 58, were recovered as effectively in HeLa cells, with or without added Mg2+, as they were in FT cells. In general, rhinoviruses were less efficiently recovered in HeLa cells; however, certain serotypes may be detected better by HeLa cells."}
{"id": "PMID:191469", "title": "Isolation of simian virus 40 from a newborn child.", "content": "Rubella virus and simina virus 40 (SV40) were isolated from a newborn child suffering from neurological and anatomical anomalies. The SV40 isolate was very similar to SV40 strain 777 by electron microscopic, biological, and immunological criteria.", "contents": "Isolation of simian virus 40 from a newborn child. Rubella virus and simina virus 40 (SV40) were isolated from a newborn child suffering from neurological and anatomical anomalies. The SV40 isolate was very similar to SV40 strain 777 by electron microscopic, biological, and immunological criteria."}
{"id": "PMID:191470", "title": "Inhibition of thyroid-stimulating hormone stimulation of protein kinase, glucose oxidation, and phospholipid synthesis in thyroid slices previously exposed to the hormone.", "content": "Prior exposure of thyroid slices to thyrotropin (TSH) induced refractoriness to subsequent stimulation of the cyclic AMP system by the hormone. Although the inhibition is incomplete, we examined whether the reduction in cyclic AMP was sufficient to alter other metabolic effects of TSH. Bovine or dog thyroid slices were incubated with or without 5-100 mU/ml TSH for 1-2h, washed, and then incubated without hormone for 1-2h. Half of the slices not exposed to TSH initially were then incubated with buffer and half were exposed to 5-100 mU/ml TSH. Slices initially incubated with TSH were also incubated with or without TSH in the third incubation. During the refractory period, TSH activation of protein kinase was inhibited even though the hormone still caused some increase in cyclic AMP concentrations. However, protein kinase activity was fully responsive to dibutyryl cyclic AMP when slices were incubated with it during the third incubation. Stimulation of glucose oxidation by TSH was significantly decreased in thyroid slices previously incubated with the hormone. During refractoriness, stimulation of glucose oxidation caused by prostaglandin E1 and dibutyryl cyclic AMP was also significantly diminished but that due to acetylcholine was not. Thus even though dibutyryl cyclic AMP could fully activate protein kinase activity during refractoriness, its effect on glucose oxidation was still inhibited, suggesting that the metabolic block responsible for this refractoriness was distal to activation of protein kinase. Stimulation of 32Pi incorporation into phospholipid by TSH and acetylcholine was also inhibited during refractoriness. Despite reduction of the stimulatory effect of TSH, binding of 125ITSH was not modified by prior incubation of thyroid slices with TSH. These results indicate that changes in the TSH  receptor are not responsible for the development of refractoriness and other metabolic sites besides activation of adenylate cyclase appear to be involved.", "contents": "Inhibition of thyroid-stimulating hormone stimulation of protein kinase, glucose oxidation, and phospholipid synthesis in thyroid slices previously exposed to the hormone. Prior exposure of thyroid slices to thyrotropin (TSH) induced refractoriness to subsequent stimulation of the cyclic AMP system by the hormone. Although the inhibition is incomplete, we examined whether the reduction in cyclic AMP was sufficient to alter other metabolic effects of TSH. Bovine or dog thyroid slices were incubated with or without 5-100 mU/ml TSH for 1-2h, washed, and then incubated without hormone for 1-2h. Half of the slices not exposed to TSH initially were then incubated with buffer and half were exposed to 5-100 mU/ml TSH. Slices initially incubated with TSH were also incubated with or without TSH in the third incubation. During the refractory period, TSH activation of protein kinase was inhibited even though the hormone still caused some increase in cyclic AMP concentrations. However, protein kinase activity was fully responsive to dibutyryl cyclic AMP when slices were incubated with it during the third incubation. Stimulation of glucose oxidation by TSH was significantly decreased in thyroid slices previously incubated with the hormone. During refractoriness, stimulation of glucose oxidation caused by prostaglandin E1 and dibutyryl cyclic AMP was also significantly diminished but that due to acetylcholine was not. Thus even though dibutyryl cyclic AMP could fully activate protein kinase activity during refractoriness, its effect on glucose oxidation was still inhibited, suggesting that the metabolic block responsible for this refractoriness was distal to activation of protein kinase. Stimulation of 32Pi incorporation into phospholipid by TSH and acetylcholine was also inhibited during refractoriness. Despite reduction of the stimulatory effect of TSH, binding of 125ITSH was not modified by prior incubation of thyroid slices with TSH. These results indicate that changes in the TSH  receptor are not responsible for the development of refractoriness and other metabolic sites besides activation of adenylate cyclase appear to be involved."}
{"id": "PMID:191471", "title": "Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase.", "content": "Cultured endothelial cells provide a model for the study of interactions of vasoactive peptides with endothelium. Endothelial cell cultured from veins of human umbilical cords contain both angiotensin I converting enzyme (kininase II) and angiotensinase activities. Intact monolayers of cells can both activate angiotensin I and inactivate bradykinin when the peptides are added to culture flasks in protein-free medium. Intact suspended cells or lysed cells convert angiotensin I to angiotensin II, inactivate bradykinin, and hydrolyze hippuryldiglycine to hippuric acid and diglycine. These actions are inhibited by SQ 20881, the specific inhibitor of converting enzyme. The kininase activity of endothelial cells was partially inhibited by antibody to human lung converting enzyme. Endothelial cells also inactivate longer analogs of bradykinin, such as kallidin, methionyl-lysyl bradykinin, and bradykinin coupled covalently to 500,000 mol wt dextran. The endothelial cells retained converting enzyme activity through four successive subcultures, indicating that the enzyme is synthesized by the cells surface, and it is apparently a marker for endothelial cells, since cultured human fibroblasts, smooth muscle cells, and baby hamster kidney cells do not have it. Endothelial cells also contain an aminopheptidase which hydrolyzes both angiotensin II and the synthetic substrate, alpha-L-aspartyl beta-naphthylamide. The angiotensinase activity increased when the cells were lysed, which suggests that the enzyme is localized within the cells, Hydrolysis of both alpha-L-aspartyl beta-naphthylamide and angiotensin II was inhibited by omicron-phenanthroline, indicating that the enzyme is an A-tipe anigotensinase.", "contents": "Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase. Cultured endothelial cells provide a model for the study of interactions of vasoactive peptides with endothelium. Endothelial cell cultured from veins of human umbilical cords contain both angiotensin I converting enzyme (kininase II) and angiotensinase activities. Intact monolayers of cells can both activate angiotensin I and inactivate bradykinin when the peptides are added to culture flasks in protein-free medium. Intact suspended cells or lysed cells convert angiotensin I to angiotensin II, inactivate bradykinin, and hydrolyze hippuryldiglycine to hippuric acid and diglycine. These actions are inhibited by SQ 20881, the specific inhibitor of converting enzyme. The kininase activity of endothelial cells was partially inhibited by antibody to human lung converting enzyme. Endothelial cells also inactivate longer analogs of bradykinin, such as kallidin, methionyl-lysyl bradykinin, and bradykinin coupled covalently to 500,000 mol wt dextran. The endothelial cells retained converting enzyme activity through four successive subcultures, indicating that the enzyme is synthesized by the cells surface, and it is apparently a marker for endothelial cells, since cultured human fibroblasts, smooth muscle cells, and baby hamster kidney cells do not have it. Endothelial cells also contain an aminopheptidase which hydrolyzes both angiotensin II and the synthetic substrate, alpha-L-aspartyl beta-naphthylamide. The angiotensinase activity increased when the cells were lysed, which suggests that the enzyme is localized within the cells, Hydrolysis of both alpha-L-aspartyl beta-naphthylamide and angiotensin II was inhibited by omicron-phenanthroline, indicating that the enzyme is an A-tipe anigotensinase."}
{"id": "PMID:191472", "title": "Alpha-1-antitrypsin bodies in the liver.", "content": "The cytoplasmic bodies in hepatocytes thought to indicate possession of the Z allele for alpha 1-antitrypsin deficiency were found in necropsy in 10 of 64 adults with cirrhosis, four of nine with hepatic fibrosis, and four of 15 with hepatocellular carcinoma. They were also found in six of 76 adults with severe panacinar emphysema, and in four of a control series of 110 adults with neither emphysema nor liver disease. The association of the bodies with each of the three liver diseases was statistically significant, but the association of the bodies with emphysema was not. It is considered probable that heterozygous (PiMZ) alpha 1-antitrypsin deficiency is associated with an increased incidence of cirrhosis, hepatic fibrosis, and hepatocellular carcinoma.", "contents": "Alpha-1-antitrypsin bodies in the liver. The cytoplasmic bodies in hepatocytes thought to indicate possession of the Z allele for alpha 1-antitrypsin deficiency were found in necropsy in 10 of 64 adults with cirrhosis, four of nine with hepatic fibrosis, and four of 15 with hepatocellular carcinoma. They were also found in six of 76 adults with severe panacinar emphysema, and in four of a control series of 110 adults with neither emphysema nor liver disease. The association of the bodies with each of the three liver diseases was statistically significant, but the association of the bodies with emphysema was not. It is considered probable that heterozygous (PiMZ) alpha 1-antitrypsin deficiency is associated with an increased incidence of cirrhosis, hepatic fibrosis, and hepatocellular carcinoma."}
{"id": "PMID:191473", "title": "25-Hydroxyvitamin D levels in patients treated with high-dosage ergo- and cholecalciferol.", "content": "25-Hydroxyvitamin D (25-OHD) levels were measured in 39 patients with metabolic bone disease or hypoparathyroidism who had been treated with a constant high dose of vitamin D2 or D3 for at least 12 weeks. Plasma 25-OHD levels rose with increasing dosage, the relationship between dose and plasma level being approximately linear whether or not the dose was expressed on a weight-corrected basis. A therapeutic range of 25-OHD to be expected when patients with these conditions are treated with vitamin D has been established. There may be certain exceptions in which plasma 25-OHD levels within the range are associated with either an inadequate response to treatment or, conversely, the hypercalcaemia of vitamin D toxicity. There was no correlation between plasma calcium level and 25-OHD concentration in the group of patients studied. There was also no difference between the dose/25-OHD relationship of patients treated with vitamin D2 and that of patients receiving vitamin D3. Ten patients were started on treatment with large doses of vitamin D during the period of the study. The rate of rise of plasma 25-OHD was followed during treatment. The incremental rise in 25-OHD was calculated at the end of the first week of treatment in terms of dose per unit body weight. The rate of rise of plasma 25-OHD level was highly correlated with the dose used. Plasma 25-OHD levels after one weeks' treatment were only 15-20% of the expected steady-state level on the same dosage. The importance of a high priming dose when a rapid response is needed is thus emphasised.", "contents": "25-Hydroxyvitamin D levels in patients treated with high-dosage ergo- and cholecalciferol. 25-Hydroxyvitamin D (25-OHD) levels were measured in 39 patients with metabolic bone disease or hypoparathyroidism who had been treated with a constant high dose of vitamin D2 or D3 for at least 12 weeks. Plasma 25-OHD levels rose with increasing dosage, the relationship between dose and plasma level being approximately linear whether or not the dose was expressed on a weight-corrected basis. A therapeutic range of 25-OHD to be expected when patients with these conditions are treated with vitamin D has been established. There may be certain exceptions in which plasma 25-OHD levels within the range are associated with either an inadequate response to treatment or, conversely, the hypercalcaemia of vitamin D toxicity. There was no correlation between plasma calcium level and 25-OHD concentration in the group of patients studied. There was also no difference between the dose/25-OHD relationship of patients treated with vitamin D2 and that of patients receiving vitamin D3. Ten patients were started on treatment with large doses of vitamin D during the period of the study. The rate of rise of plasma 25-OHD was followed during treatment. The incremental rise in 25-OHD was calculated at the end of the first week of treatment in terms of dose per unit body weight. The rate of rise of plasma 25-OHD level was highly correlated with the dose used. Plasma 25-OHD levels after one weeks' treatment were only 15-20% of the expected steady-state level on the same dosage. The importance of a high priming dose when a rapid response is needed is thus emphasised."}
{"id": "PMID:191474", "title": "Morphology and the natural history of cribriform adenocarcinoma (adenoid cystic carcinoma).", "content": "Forty-three examples of cribriform adenocarcinoma (adenoid cystic carcinoma) of mixed glandular origin are reported. Structural studies emphasise the classical cribriform pattern which indicates the capacity of this neoplasm to behave as both an epithelial and a connective tissue type tumour. In terms of survival, it does not appear to be an malignant as other forms of carcinoma arising in similar anatomical locations. The five-year crude survival rate (56%) compares favourably with that of other carcinomas of the palate and paranasal sinuses. A recurrence rate of the order of 20% may persist up to 10 years after primary treatment, and while this is not inimical to longer survival there is clearly a high morbidity.", "contents": "Morphology and the natural history of cribriform adenocarcinoma (adenoid cystic carcinoma). Forty-three examples of cribriform adenocarcinoma (adenoid cystic carcinoma) of mixed glandular origin are reported. Structural studies emphasise the classical cribriform pattern which indicates the capacity of this neoplasm to behave as both an epithelial and a connective tissue type tumour. In terms of survival, it does not appear to be an malignant as other forms of carcinoma arising in similar anatomical locations. The five-year crude survival rate (56%) compares favourably with that of other carcinomas of the palate and paranasal sinuses. A recurrence rate of the order of 20% may persist up to 10 years after primary treatment, and while this is not inimical to longer survival there is clearly a high morbidity."}
{"id": "PMID:191475", "title": "The mobile receptor hypothesis in hormone action: a general model accounting for desensitization.", "content": "The characteristics of the hormone interaction with their cell receptors and of the related adenylate cyclase activation are complex. Among the theoretical models which have been proposed to account for this mechanism, the mobile or floating receptor model has been discussed (3-5). The purpose of this work is to deduce several particular models from the general mobile receptor model on the basis of thermodynamic considerations. The analysis of some of these models shows that the mobile receptor hypothesis contains in itself the little understood kinetic phenomenon of hormone desensitization.", "contents": "The mobile receptor hypothesis in hormone action: a general model accounting for desensitization. The characteristics of the hormone interaction with their cell receptors and of the related adenylate cyclase activation are complex. Among the theoretical models which have been proposed to account for this mechanism, the mobile or floating receptor model has been discussed (3-5). The purpose of this work is to deduce several particular models from the general mobile receptor model on the basis of thermodynamic considerations. The analysis of some of these models shows that the mobile receptor hypothesis contains in itself the little understood kinetic phenomenon of hormone desensitization."}
{"id": "PMID:191476", "title": "The involvement of prostaglandin endoperoxide formation in the elevation of cyclic GMP levels during platelet aggregation.", "content": "Arachidonic acid- or collagen-induced aggregation was accompanied by a progressive elevation in the level of cyclic GMP in washed human platelets with no significant alteration in the concentration of cyclic AMP. The extent of the increase in cyclic GMP was proportional to the concentration of arachidonic acid added. Enhanced accumulation of cyclic GMP produced by arachidonic or collagen was prevented by prior exposure of platelets to aspirin or indomethacin. Prostaglandin endoperoxide G2 caused platelet aggregation and an increase in cyclic GMP concentration; neither event was blocked by prostaglandin synthesis inhibitors. These results indicate that the generation of prostaglandin endoperoxides is a step in the sequence of events in platelet aggregation leading to the enhanced accumulation of cyclic GMP.", "contents": "The involvement of prostaglandin endoperoxide formation in the elevation of cyclic GMP levels during platelet aggregation. Arachidonic acid- or collagen-induced aggregation was accompanied by a progressive elevation in the level of cyclic GMP in washed human platelets with no significant alteration in the concentration of cyclic AMP. The extent of the increase in cyclic GMP was proportional to the concentration of arachidonic acid added. Enhanced accumulation of cyclic GMP produced by arachidonic or collagen was prevented by prior exposure of platelets to aspirin or indomethacin. Prostaglandin endoperoxide G2 caused platelet aggregation and an increase in cyclic GMP concentration; neither event was blocked by prostaglandin synthesis inhibitors. These results indicate that the generation of prostaglandin endoperoxides is a step in the sequence of events in platelet aggregation leading to the enhanced accumulation of cyclic GMP."}
{"id": "PMID:191477", "title": "Decrease in calcium transport associated with phosphoprotein phosphatase-catalyzed dephosphorylation of cardiac sarcoplasmic reticulum.", "content": "Phosphoprotein phosphatase activity is found in preparations of sarcoplasmic reticulum isolated from canine heart when assayed with either phosphate or phosphorylated sarcoplasmic reticulum as substrate. Phosphoprotein phosphatase-catalyzed dephosphorylation of the 22,000 dalton phosphoprotein of cardiac sarcoplasmic reticulum is stimulated markedly by MnCl2 (5 mM) and to a lesser extent by MgCl2 (5 mM); inorganic phosphate (50 mM) and NaF (25 mM) are inhibitory. Dephosphorylation of this 22,000 dalton phosphoprotein is correlated with a decreased initial rate of calcium transport. The close structural and functional relationship of phosphoprotein phosphatase to the cardiac sarcoplasmic reticulum suggests a possible role of this enzyme in reversing the relaxation-promoting effects of catecholamines on the intact heart.", "contents": "Decrease in calcium transport associated with phosphoprotein phosphatase-catalyzed dephosphorylation of cardiac sarcoplasmic reticulum. Phosphoprotein phosphatase activity is found in preparations of sarcoplasmic reticulum isolated from canine heart when assayed with either phosphate or phosphorylated sarcoplasmic reticulum as substrate. Phosphoprotein phosphatase-catalyzed dephosphorylation of the 22,000 dalton phosphoprotein of cardiac sarcoplasmic reticulum is stimulated markedly by MnCl2 (5 mM) and to a lesser extent by MgCl2 (5 mM); inorganic phosphate (50 mM) and NaF (25 mM) are inhibitory. Dephosphorylation of this 22,000 dalton phosphoprotein is correlated with a decreased initial rate of calcium transport. The close structural and functional relationship of phosphoprotein phosphatase to the cardiac sarcoplasmic reticulum suggests a possible role of this enzyme in reversing the relaxation-promoting effects of catecholamines on the intact heart."}
{"id": "PMID:191478", "title": "Milk fever in dairy cows. VIII. Effect of injected vitamin D3 and calcium and phosphorus intake on incidence.", "content": "In a field trial, effects of prepartal intermuscular injection of 10 million units of vitamin D3 on incidence of milk fever were examined both in relation to intake of calcium and phosphorous during the dry period and previous history of milk fever. Based upon intake of calcium and phosphorus cooperating herds were grouped as feeding: 1) greater than .53% of the total ration dry matter as calcium and greater than .28% as phosphorus: 2) less than .47% as calcium and greater than .28% as phosphorus; 3) greater than .47% to less than .53% as calcium and greater than .22% to less than .28% as phosphorus. Injections of vitamin D3 given approximately 1 wk prepartum reduced incidence of milk fever in cows with previous history of milk fever in all three groups but had no effect in cows with no previous milk fever. Incidence of milk fever was lower in group 3 than for cows of groups 1 and 2 with previous milk fever and than for cows of group 1 with no previous history. The results indicate that careful control of calcium and phosphorus intake during the dry period at .5% calcium and .25% phosphorus of the dry matter of the total ration will limit milk fever incidence to about 10%. Injections of vitamin D3 as described will reduce inicidence of milk fever further in cows with previous milk fever but not in cows with no previous milk fever.", "contents": "Milk fever in dairy cows. VIII. Effect of injected vitamin D3 and calcium and phosphorus intake on incidence. In a field trial, effects of prepartal intermuscular injection of 10 million units of vitamin D3 on incidence of milk fever were examined both in relation to intake of calcium and phosphorous during the dry period and previous history of milk fever. Based upon intake of calcium and phosphorus cooperating herds were grouped as feeding: 1) greater than .53% of the total ration dry matter as calcium and greater than .28% as phosphorus: 2) less than .47% as calcium and greater than .28% as phosphorus; 3) greater than .47% to less than .53% as calcium and greater than .22% to less than .28% as phosphorus. Injections of vitamin D3 given approximately 1 wk prepartum reduced incidence of milk fever in cows with previous history of milk fever in all three groups but had no effect in cows with no previous milk fever. Incidence of milk fever was lower in group 3 than for cows of groups 1 and 2 with previous milk fever and than for cows of group 1 with no previous history. The results indicate that careful control of calcium and phosphorus intake during the dry period at .5% calcium and .25% phosphorus of the dry matter of the total ration will limit milk fever incidence to about 10%. Injections of vitamin D3 as described will reduce inicidence of milk fever further in cows with previous milk fever but not in cows with no previous milk fever."}
{"id": "PMID:191521", "title": "The persistence of poliovirus of poliovirus in activated sludge treatment.", "content": "A model activated sludge treatment plant was used which was functionally very similar to a full scale plant. It was inoculated with poliovirus either continuously or with a single dose and the amounts of virus in the influent, mixed liquor and effluent were monitored regularly. The distribution of the virus in the liquid and solid phases of the mixed liquor was very unequal with about 85% of the virus associated with the suspended solids fraction. Only small amounts of virus were recovered from the effluent and after inoculation was stopped virus rapidly became indetectable. The efficiency of the plant with regard to removal of virus was closely related to its capacity to remove suspended solids and the adsorption of virus to solids and its inactivation is briefly discussed.", "contents": "The persistence of poliovirus of poliovirus in activated sludge treatment. A model activated sludge treatment plant was used which was functionally very similar to a full scale plant. It was inoculated with poliovirus either continuously or with a single dose and the amounts of virus in the influent, mixed liquor and effluent were monitored regularly. The distribution of the virus in the liquid and solid phases of the mixed liquor was very unequal with about 85% of the virus associated with the suspended solids fraction. Only small amounts of virus were recovered from the effluent and after inoculation was stopped virus rapidly became indetectable. The efficiency of the plant with regard to removal of virus was closely related to its capacity to remove suspended solids and the adsorption of virus to solids and its inactivation is briefly discussed."}
{"id": "PMID:191522", "title": "Experimental transplacental transmission of porcine cytomegalovirus.", "content": "Six serologically negative sows were infected by intranasal instillation of porcine cytomegalovirus (PCMV) between 31 and 85 days of pregnacy. Four sows showed an afebrile anorexia and lethargy 14-25 days after infection and all 6 developed significant increases in indirect immunofluorescent (IIF) antibody titres within 35 days. Virus was recovered from nasal and/or cervical swabs from 2 sows during life and from lung macrophage cultures after death. At term the sows were killed and their fetuses harvested by caesarean section. The number of mummified and stillborn fetuses increased from 4/63 in 6 previous litters to 18/60 in the 6 present litters. Nine of 43 fetuses born alive were reared in isolators for up to 6 weeks but the majority were killed for examination on the day of birth. Virus was isolated from 16 piglets from 4 of the 6 litters examined; it was isolated most frequently from lungs and liver but also from spleen, kidney, brain and nasal mucosa. Unsuckled day-old pigs had insignificant IIF titres, irrespective of whether they were excreting virus or not. The 5 congenital excretors which were reared all died within 7 days but no death occurred among their 4 litter-mates. Post-natal infection of 2 of these piglets reared in contact with congenitally infected pigs was suggested by the recovery of virus from nasal swabs 17 and 27 days after birth and the subsequent rise in IIF titre to 1/256 by day 42.", "contents": "Experimental transplacental transmission of porcine cytomegalovirus. Six serologically negative sows were infected by intranasal instillation of porcine cytomegalovirus (PCMV) between 31 and 85 days of pregnacy. Four sows showed an afebrile anorexia and lethargy 14-25 days after infection and all 6 developed significant increases in indirect immunofluorescent (IIF) antibody titres within 35 days. Virus was recovered from nasal and/or cervical swabs from 2 sows during life and from lung macrophage cultures after death. At term the sows were killed and their fetuses harvested by caesarean section. The number of mummified and stillborn fetuses increased from 4/63 in 6 previous litters to 18/60 in the 6 present litters. Nine of 43 fetuses born alive were reared in isolators for up to 6 weeks but the majority were killed for examination on the day of birth. Virus was isolated from 16 piglets from 4 of the 6 litters examined; it was isolated most frequently from lungs and liver but also from spleen, kidney, brain and nasal mucosa. Unsuckled day-old pigs had insignificant IIF titres, irrespective of whether they were excreting virus or not. The 5 congenital excretors which were reared all died within 7 days but no death occurred among their 4 litter-mates. Post-natal infection of 2 of these piglets reared in contact with congenitally infected pigs was suggested by the recovery of virus from nasal swabs 17 and 27 days after birth and the subsequent rise in IIF titre to 1/256 by day 42."}
{"id": "PMID:191523", "title": "Biologic and chemical characterization of HLA antigens in human serum.", "content": "HLA antigens of both the A and B loci were shown to be associated with the high density lipoprotein fraction of serum prepared by ultracentrifugal flotation. HLA-A9 antigens were purified 100-fold with essentially complete recovery by a simple procedure of high density lipoprotein preparation involving precipitation with polyanions and ultracentrifugal flotation. The purified lipid-associated antigen was immunogenic since it elicited the formation of cytotoxic xenoantibodies in rabbits. Serum HLA-A9 antigens were found by immunoprecipitation and gel electrophoresis to consist of a 45,000 m.w. heavy chain associated with beta2-microglobulin. The size of the HLA-lipid complex (less than 190,000 m.w.) and of the HLA-deoxycholate complex (less than 102,000 m.w.) suggests that HLA antigens are shed into plasma as a complex of a single HLA molecule and a single beta2-microglobulin chain, associated with boundary lipid.", "contents": "Biologic and chemical characterization of HLA antigens in human serum. HLA antigens of both the A and B loci were shown to be associated with the high density lipoprotein fraction of serum prepared by ultracentrifugal flotation. HLA-A9 antigens were purified 100-fold with essentially complete recovery by a simple procedure of high density lipoprotein preparation involving precipitation with polyanions and ultracentrifugal flotation. The purified lipid-associated antigen was immunogenic since it elicited the formation of cytotoxic xenoantibodies in rabbits. Serum HLA-A9 antigens were found by immunoprecipitation and gel electrophoresis to consist of a 45,000 m.w. heavy chain associated with beta2-microglobulin. The size of the HLA-lipid complex (less than 190,000 m.w.) and of the HLA-deoxycholate complex (less than 102,000 m.w.) suggests that HLA antigens are shed into plasma as a complex of a single HLA molecule and a single beta2-microglobulin chain, associated with boundary lipid."}
{"id": "PMID:191524", "title": "Cell-mediated immune responses in patients with recurrent Herpes Simplex infections. II. Infection-associated deficiency of lymphokine production in patients with recurrent herpes labialis or herpes progenitalis.", "content": "Herpes simplex virus antigen-induced lymphocyte proliferation and production of leukocyte migration inhibitory factor (LMIF) and lymphocyte-derived interferon were studied in normal individuals and patients with recurrent Herpes labialis and Herpes progenitalis. Virus-specific lymphoproliferative responses were regularly detected in patients with recurrent infection irrespective of the clinical stage of infection. In contrast, transient deficiencies in herpes-specific lymphoid production of both LMIF and interferon were regularly documented at the time of and immediately before herpes simplex-induced vesicular eruptions. During the convalescence, pronounced production of these mediators in response to antigenic stimulation with inactivated virus antigen preparations were regularly detected. The biology of these fluctuations in lymphokine production is evaluated and discussed.", "contents": "Cell-mediated immune responses in patients with recurrent Herpes Simplex infections. II. Infection-associated deficiency of lymphokine production in patients with recurrent herpes labialis or herpes progenitalis. Herpes simplex virus antigen-induced lymphocyte proliferation and production of leukocyte migration inhibitory factor (LMIF) and lymphocyte-derived interferon were studied in normal individuals and patients with recurrent Herpes labialis and Herpes progenitalis. Virus-specific lymphoproliferative responses were regularly detected in patients with recurrent infection irrespective of the clinical stage of infection. In contrast, transient deficiencies in herpes-specific lymphoid production of both LMIF and interferon were regularly documented at the time of and immediately before herpes simplex-induced vesicular eruptions. During the convalescence, pronounced production of these mediators in response to antigenic stimulation with inactivated virus antigen preparations were regularly detected. The biology of these fluctuations in lymphokine production is evaluated and discussed."}
{"id": "PMID:191525", "title": "Human monocyte-macrophage-mediated antibody-dependent cytotoxicity to herpes simplex virus-infected cells.", "content": "Human peripheral blood mononuclear cells which mediate antibody-dependent cellular cytotoxicity (ADCC) against herpes simplex virus- (HSV) infected target cells consist of both adherent (MA) and nonadherent (MNA) effector cell populations. These two cell populations can be distinguished by their different phagocytic properties and morphologic appearance, their requirement for antibody in the ADCC reaction, and the rapidity with which they lyse target cells in the presence of immune serum. The MA cells are predominantly phagocytic and have the morphologic characteristics of monocyte-macrophages, whereas the MNA cells are nonphagocytic and appear to be small to medium-sized lymphocytes. Optimal expression of ADCC by MA cells requires higher concentrations of immune serum than does MNA cell-mediated ADCC. MA-mediated cell killing is first detectable by 8 hr and reaches completion after 24 hr of incubation. In contrast, MNA-mediated ADCC produces target cell damage by 2 hr and reaches completion at 8 hr of incubation. Unlike MNA effector cells, the MA effector cells are profoundly inhibited after preincubation with either latex or silica particles. The HSV immune status of the donor had no effect on the ability of either cell population to mediate ADCC. These data demonstrate the participation of both nonadherent mononuclear cells, presumably K cells, and monocyte-macrophages, in ADCC directed against HSV-infected target cells.", "contents": "Human monocyte-macrophage-mediated antibody-dependent cytotoxicity to herpes simplex virus-infected cells. Human peripheral blood mononuclear cells which mediate antibody-dependent cellular cytotoxicity (ADCC) against herpes simplex virus- (HSV) infected target cells consist of both adherent (MA) and nonadherent (MNA) effector cell populations. These two cell populations can be distinguished by their different phagocytic properties and morphologic appearance, their requirement for antibody in the ADCC reaction, and the rapidity with which they lyse target cells in the presence of immune serum. The MA cells are predominantly phagocytic and have the morphologic characteristics of monocyte-macrophages, whereas the MNA cells are nonphagocytic and appear to be small to medium-sized lymphocytes. Optimal expression of ADCC by MA cells requires higher concentrations of immune serum than does MNA cell-mediated ADCC. MA-mediated cell killing is first detectable by 8 hr and reaches completion after 24 hr of incubation. In contrast, MNA-mediated ADCC produces target cell damage by 2 hr and reaches completion at 8 hr of incubation. Unlike MNA effector cells, the MA effector cells are profoundly inhibited after preincubation with either latex or silica particles. The HSV immune status of the donor had no effect on the ability of either cell population to mediate ADCC. These data demonstrate the participation of both nonadherent mononuclear cells, presumably K cells, and monocyte-macrophages, in ADCC directed against HSV-infected target cells."}
{"id": "PMID:191526", "title": "Identification of the Schwann cell as a peripheral nervous system cell possessing a differentiation antigen expressed by a human lung tumor.", "content": "Recent studies of the plasma membrane antigens of a human lung tumor (oat cell carcinoma) indicated that the tumor expressed at least two normal differentiation antigens undetectable in normal respiratory epithelium. One antigen was characteristic of certain endodermally derived epithelial cells of the digestive system; the other antigen was characteristic of certain neural crest-derived cells in the peripheral nervous system. The present studies were undertaken to identify the reactive cell type in the peripheral nervous system. Since similar cells in the rat peripheral nervous system expressed a cross-reactive form of this antigen, and since pure cultures of different rat nerve cell type were available, the following approach was possible. Cultures of pure neurons, pure Schwann cells, pure fibroblasts, neurons and Schwann cells, and neurons, Schwann cells, and fibroblasts were assayed for this antigen with rabbit anti-oat cell carcinoma plasma membrane antiserum absorbed with normal lung and liver. The indirect immunofluorescence method on both whole, viable cell and fixed cell substrates was used. Only Schwann cells expressed the antigen; Schwann cells in the presence of neurons expressed the antigen much more strongly than did pure Schwann cells. It was concluded that the oat cell carcinoma of the lung expressed a differentiation antigen present on Schwann cells.", "contents": "Identification of the Schwann cell as a peripheral nervous system cell possessing a differentiation antigen expressed by a human lung tumor. Recent studies of the plasma membrane antigens of a human lung tumor (oat cell carcinoma) indicated that the tumor expressed at least two normal differentiation antigens undetectable in normal respiratory epithelium. One antigen was characteristic of certain endodermally derived epithelial cells of the digestive system; the other antigen was characteristic of certain neural crest-derived cells in the peripheral nervous system. The present studies were undertaken to identify the reactive cell type in the peripheral nervous system. Since similar cells in the rat peripheral nervous system expressed a cross-reactive form of this antigen, and since pure cultures of different rat nerve cell type were available, the following approach was possible. Cultures of pure neurons, pure Schwann cells, pure fibroblasts, neurons and Schwann cells, and neurons, Schwann cells, and fibroblasts were assayed for this antigen with rabbit anti-oat cell carcinoma plasma membrane antiserum absorbed with normal lung and liver. The indirect immunofluorescence method on both whole, viable cell and fixed cell substrates was used. Only Schwann cells expressed the antigen; Schwann cells in the presence of neurons expressed the antigen much more strongly than did pure Schwann cells. It was concluded that the oat cell carcinoma of the lung expressed a differentiation antigen present on Schwann cells."}
{"id": "PMID:191527", "title": "Stimulation of human peripheral blood lymphocytes by periodate, galactose oxidase, soybean agglutinin, and peanut agglutinin: differential effects of adherent cells.", "content": "Blastogenic responses of normal human peripheral lymphocytes to three distinct groups of mitogens were studied: Group I--phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM); Group II--soybean agglutinin (SBA) and peanut agglutinin (PNA); and Group III--galactose oxidase (GO) and sodium periodate (IO4-). SBA was mitogenic for human cells, and this effect was enhanced by treating the cells with neuraminidase (NA). PNA was mitogenic only after cells had been treated with NA. GO was effective before and activity was increased after lymphocytes were treated with NA. Responses to Group II and III mitogens were more variable than were those to Group I mitogens. Studies with purified T and B cells indicated that SBA and PNA were T cell mitogens, whereas IO4- and GO failed to stimulate either T or B cells. Adding macrophages back to this system indicated that they were both T cell mitogens with strict macrophage requirements. T cell responses to SBA and PNA were enhanced over responses to unfractionated cells to a degree that could not be explained simply by enrichment of the cultures with T cells. Removal of adherent cells from unfractionated cell suspensions again revealed a marked enhancement of responses to SBA and PNA, a consistent decrease in responses to IO4-, and a variable decrease in responses to GO. Similar results were found with 14C-leucine and 3H-uridine incorporation,  as well as 3H-thymidine for the assessment of bastogenic response. Mechanisms responsible for these differential effects of macrophage depletion on lymphocyte responses to different groups of mitogens are yet to be determined. Either different mitogens require different lymphocyte to macrophage ratios for optimal stimulation, or some mitogens (i.e., SBA and PNA) form inhibitory complexees in the lymphocyte-macrophage mixture. In any case, variability in response to mitogenic agents in normal as well as pathologic states may be dependent on adherent cell populations, rather than on the lymphocytes themselves.", "contents": "Stimulation of human peripheral blood lymphocytes by periodate, galactose oxidase, soybean agglutinin, and peanut agglutinin: differential effects of adherent cells. Blastogenic responses of normal human peripheral lymphocytes to three distinct groups of mitogens were studied: Group I--phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM); Group II--soybean agglutinin (SBA) and peanut agglutinin (PNA); and Group III--galactose oxidase (GO) and sodium periodate (IO4-). SBA was mitogenic for human cells, and this effect was enhanced by treating the cells with neuraminidase (NA). PNA was mitogenic only after cells had been treated with NA. GO was effective before and activity was increased after lymphocytes were treated with NA. Responses to Group II and III mitogens were more variable than were those to Group I mitogens. Studies with purified T and B cells indicated that SBA and PNA were T cell mitogens, whereas IO4- and GO failed to stimulate either T or B cells. Adding macrophages back to this system indicated that they were both T cell mitogens with strict macrophage requirements. T cell responses to SBA and PNA were enhanced over responses to unfractionated cells to a degree that could not be explained simply by enrichment of the cultures with T cells. Removal of adherent cells from unfractionated cell suspensions again revealed a marked enhancement of responses to SBA and PNA, a consistent decrease in responses to IO4-, and a variable decrease in responses to GO. Similar results were found with 14C-leucine and 3H-uridine incorporation,  as well as 3H-thymidine for the assessment of bastogenic response. Mechanisms responsible for these differential effects of macrophage depletion on lymphocyte responses to different groups of mitogens are yet to be determined. Either different mitogens require different lymphocyte to macrophage ratios for optimal stimulation, or some mitogens (i.e., SBA and PNA) form inhibitory complexees in the lymphocyte-macrophage mixture. In any case, variability in response to mitogenic agents in normal as well as pathologic states may be dependent on adherent cell populations, rather than on the lymphocytes themselves."}
{"id": "PMID:191528", "title": "Cell-mediated immune responses in recurrent herpesvirus infections. I. Lymphocyte proliferation assay.", "content": "Studies in immunosuppressed and immunodeficient patients indicate that the cell-mediated immune response appears to be responsible for controlling reactivated herpesvirus infections. In this study, the various parameters of a herpesvirus (types 1 and 2) antigen specific lymphocyte proliferation assay were optimized and used to evaluate individuals with clinical, recurrent HSV-1 and HSV-2 infections. Normal individuals with neutralizing antibody to HSV-1 or HSV-2 responded to virus antigen in culture as well as individuals with recurrent disease. Normal individuals without neutralizing antibody responded with a significantly lower response. Specificity of the lymphocyte proliferation assay was observed most strikingly in normal individuals with a rare HSV-1 infection during the vesicular eruption. Specificity was also observed by determining the ratio of the response to HSV-1 as compared to the response to HSV-2. Evaluated in this manner, individuals with recurrent HSV-1 infections had significantly higher ratios than individuals with HSV-2 infections and vice versa. Data from individuals with recurrent disease was compared to that of normal individuals to determine whether the former demonstrated a specific alteration in this response. Individuals with recurrent disease were found to have higher neutralizing antibody titers than normals. The neutralizing antibody titers in normal individuals correlated well with the lymphocyte proliferation assay results, whereas a similar evaluation in individuals with recurrent disease gave a negative correlation. The ratio of HSV-1 response/HSV-2 response also demonstrated a suppressed response in recurrent infections to the homologous virus during active disease, which disappeared when the individual was convalescent. These studies indicate that individuals with recurrent HSV infections have virus antigen specific alterations of their cell-mediated immune response, which can be associated with their disease.", "contents": "Cell-mediated immune responses in recurrent herpesvirus infections. I. Lymphocyte proliferation assay. Studies in immunosuppressed and immunodeficient patients indicate that the cell-mediated immune response appears to be responsible for controlling reactivated herpesvirus infections. In this study, the various parameters of a herpesvirus (types 1 and 2) antigen specific lymphocyte proliferation assay were optimized and used to evaluate individuals with clinical, recurrent HSV-1 and HSV-2 infections. Normal individuals with neutralizing antibody to HSV-1 or HSV-2 responded to virus antigen in culture as well as individuals with recurrent disease. Normal individuals without neutralizing antibody responded with a significantly lower response. Specificity of the lymphocyte proliferation assay was observed most strikingly in normal individuals with a rare HSV-1 infection during the vesicular eruption. Specificity was also observed by determining the ratio of the response to HSV-1 as compared to the response to HSV-2. Evaluated in this manner, individuals with recurrent HSV-1 infections had significantly higher ratios than individuals with HSV-2 infections and vice versa. Data from individuals with recurrent disease was compared to that of normal individuals to determine whether the former demonstrated a specific alteration in this response. Individuals with recurrent disease were found to have higher neutralizing antibody titers than normals. The neutralizing antibody titers in normal individuals correlated well with the lymphocyte proliferation assay results, whereas a similar evaluation in individuals with recurrent disease gave a negative correlation. The ratio of HSV-1 response/HSV-2 response also demonstrated a suppressed response in recurrent infections to the homologous virus during active disease, which disappeared when the individual was convalescent. These studies indicate that individuals with recurrent HSV infections have virus antigen specific alterations of their cell-mediated immune response, which can be associated with their disease."}
{"id": "PMID:191529", "title": "Specificities of killing by cytotoxic lymphocytes generated in vivo and in vitro to syngeneic SV40 transformed cells.", "content": "Cell-mediated immunity to SV40-transformed C3H and C3H-SW cell lines was measured by using both 51Cr and 125IUdR release assays. Killing by cytotoxic cells generated on in vitro sensitization of immune spleen cells with syngeneic SV40 cells by either assay is specific for syngeneic SV40 transformants. Cytolysis mediated by in vitro sensitized cells is ablated by treatment of the effector cells with anti-theta serum and complement. Intraperitoneal immunization with syngeneic SV40 cells yields two distinct killer-cell populations in the peritoneal exudate when assayed by 125IUdR release. The first, nylon wool nonadherent and sensitive to anti-theta and complement, is indistinguishable from the killers generated in vitro. The second population, present in larger numbers and more efficient on a per-cell basis in killing of SV40 targets than the first, is nylon adherent and is not removed by treatment with anti-theta and complement. This second population will kill any SV40 transformed target, whether syngeneic or allogeneic. The possible roles of T cell and non-T cell effectors in rejection of syngeneic SV40 tumors are discussed.", "contents": "Specificities of killing by cytotoxic lymphocytes generated in vivo and in vitro to syngeneic SV40 transformed cells. Cell-mediated immunity to SV40-transformed C3H and C3H-SW cell lines was measured by using both 51Cr and 125IUdR release assays. Killing by cytotoxic cells generated on in vitro sensitization of immune spleen cells with syngeneic SV40 cells by either assay is specific for syngeneic SV40 transformants. Cytolysis mediated by in vitro sensitized cells is ablated by treatment of the effector cells with anti-theta serum and complement. Intraperitoneal immunization with syngeneic SV40 cells yields two distinct killer-cell populations in the peritoneal exudate when assayed by 125IUdR release. The first, nylon wool nonadherent and sensitive to anti-theta and complement, is indistinguishable from the killers generated in vitro. The second population, present in larger numbers and more efficient on a per-cell basis in killing of SV40 targets than the first, is nylon adherent and is not removed by treatment with anti-theta and complement. This second population will kill any SV40 transformed target, whether syngeneic or allogeneic. The possible roles of T cell and non-T cell effectors in rejection of syngeneic SV40 tumors are discussed."}
{"id": "PMID:191530", "title": "Characterization of the blastogenic and cytotoxic responses of normal mice to ecotropic C-type viral gp71.", "content": "Spleen cells from normal (B6C3)F1 mice demonstrated natural cytotoxic reactivity mediated by a \"null\" cell population which, in part, had immunologic specificity for the major envelope glycoprotein (gp71) of the endogenous ecotropic murine leukemia virus. In contrast, the cytotoxic reactivity reflected in spleen cells of NIH Swiss nude mice apparently had no immunologic specificity. A significant level of blastogenic response could be generated in vitro by using normal (B6C3)F1 and AKR spleen cells in the presence of gp71. This reactivity was highly type specific. Moreover, using normal spleen cells from (B6C3)F1, both secondary blastogenic responses and cytotoxic T cell responses could be induced in vitro with purified soluble viral gp71. These findings extend further our previous studies on the existence of a natural immune response in normal mice to their endogenous MuLV by providing in vitro evidence for the expression of cell-mediated response in addition to the humoral response and that at least two effector cell types are operable in the cell-mediated phase.", "contents": "Characterization of the blastogenic and cytotoxic responses of normal mice to ecotropic C-type viral gp71. Spleen cells from normal (B6C3)F1 mice demonstrated natural cytotoxic reactivity mediated by a \"null\" cell population which, in part, had immunologic specificity for the major envelope glycoprotein (gp71) of the endogenous ecotropic murine leukemia virus. In contrast, the cytotoxic reactivity reflected in spleen cells of NIH Swiss nude mice apparently had no immunologic specificity. A significant level of blastogenic response could be generated in vitro by using normal (B6C3)F1 and AKR spleen cells in the presence of gp71. This reactivity was highly type specific. Moreover, using normal spleen cells from (B6C3)F1, both secondary blastogenic responses and cytotoxic T cell responses could be induced in vitro with purified soluble viral gp71. These findings extend further our previous studies on the existence of a natural immune response in normal mice to their endogenous MuLV by providing in vitro evidence for the expression of cell-mediated response in addition to the humoral response and that at least two effector cell types are operable in the cell-mediated phase."}
{"id": "PMID:191531", "title": "Influence of H-2 complex on susceptibility to infection by murine leukemia virus.", "content": "Titers of infectious ecotropic MuLV in mouse spleen were examined after deliberate infection. In congenic mice differing only in H-2 haplotype, a gene (or genes) within the H-2 complex determined either a high virus titer (H-2k, H-2d, H-2a) or a low titer (H-2b, H-2q). Susceptibility to high virus titers was inherited as a dominant trait. Kinetic studies revealed similar initial patterns of infection in both groups, with a fall in titer in the \"resistant\" strain occurring from week 6 through 10 after infection. Anti-VEA antibody titers differed significantly between the groups, but no mechanistic role for antibody in eliminating virus was apparent. Genes outside the H-2 complex were shown to influence MuLV titers after infection as well.", "contents": "Influence of H-2 complex on susceptibility to infection by murine leukemia virus. Titers of infectious ecotropic MuLV in mouse spleen were examined after deliberate infection. In congenic mice differing only in H-2 haplotype, a gene (or genes) within the H-2 complex determined either a high virus titer (H-2k, H-2d, H-2a) or a low titer (H-2b, H-2q). Susceptibility to high virus titers was inherited as a dominant trait. Kinetic studies revealed similar initial patterns of infection in both groups, with a fall in titer in the \"resistant\" strain occurring from week 6 through 10 after infection. Anti-VEA antibody titers differed significantly between the groups, but no mechanistic role for antibody in eliminating virus was apparent. Genes outside the H-2 complex were shown to influence MuLV titers after infection as well."}
{"id": "PMID:191532", "title": "Stimulation of mouse migration inhibitory factor (MIF) production form MSV-immune lymphocytes by soluble tumor-associated antigen: requirement for histocompatible macrophages.", "content": "Spleen cells from C57BL/6 mice immunized with murine sarcoma virus (MSV) are capable of producing migration inhibition factor (MIF) in response to stimulation with a specific tumor-associated antigen prepared by solubilization with 3 M KCL. We have previously demonstrated that this response is T cell-dependent. Further investigations into the effector cells involved in the production of MIF have revealed that spleen cells from mice immunized with MSV cannot produce MIF when stimulated with tumor extract if the population has been previously depleted of macrophages. However, the response can be restored by adding nonimmune syngeneic macrophages but not by allogeneic macrophages. The inability of allogeneic macrophages to provide this function was not due to their increased suppressor activity since in mixing experiments they did not interfere with the ability of immune spleen cells to produce MIF. Furthermore, they were not defective since they could supply this \"cooperative function\" to appropriate F1 mice. The results indicate that macrophages are required for stimulation of MIF by soluble tumor antigens and that for efficient interaction the macrophages and lymphocytes must share some genetic similarities.", "contents": "Stimulation of mouse migration inhibitory factor (MIF) production form MSV-immune lymphocytes by soluble tumor-associated antigen: requirement for histocompatible macrophages. Spleen cells from C57BL/6 mice immunized with murine sarcoma virus (MSV) are capable of producing migration inhibition factor (MIF) in response to stimulation with a specific tumor-associated antigen prepared by solubilization with 3 M KCL. We have previously demonstrated that this response is T cell-dependent. Further investigations into the effector cells involved in the production of MIF have revealed that spleen cells from mice immunized with MSV cannot produce MIF when stimulated with tumor extract if the population has been previously depleted of macrophages. However, the response can be restored by adding nonimmune syngeneic macrophages but not by allogeneic macrophages. The inability of allogeneic macrophages to provide this function was not due to their increased suppressor activity since in mixing experiments they did not interfere with the ability of immune spleen cells to produce MIF. Furthermore, they were not defective since they could supply this \"cooperative function\" to appropriate F1 mice. The results indicate that macrophages are required for stimulation of MIF by soluble tumor antigens and that for efficient interaction the macrophages and lymphocytes must share some genetic similarities."}
{"id": "PMID:191533", "title": "A comparative study of detection methods for Aleutian disease viral antibody.", "content": "Four methods of detecting and quantitating mink antibody against Aleutian disease (AD) virus were compared. Counterelectrophoresis, modified, counterelectrophoresis, immunofluorescence, and complement fixation were performed blindly on 274 serum samples. All four methods were reliably specific for AD antibody. Immunofluorescence was less reproducible than the other systems. Immunofluorescence complement fixation were 4- to 8-fold more sensitive than regular or modified counterelectrophoresis, but were limited by background staining and anti-complementary activity, respectively, when used to detect small amounts of antibody in undiluted sera.", "contents": "A comparative study of detection methods for Aleutian disease viral antibody. Four methods of detecting and quantitating mink antibody against Aleutian disease (AD) virus were compared. Counterelectrophoresis, modified, counterelectrophoresis, immunofluorescence, and complement fixation were performed blindly on 274 serum samples. All four methods were reliably specific for AD antibody. Immunofluorescence was less reproducible than the other systems. Immunofluorescence complement fixation were 4- to 8-fold more sensitive than regular or modified counterelectrophoresis, but were limited by background staining and anti-complementary activity, respectively, when used to detect small amounts of antibody in undiluted sera."}
{"id": "PMID:191534", "title": "Studies of H-2 restriction in cell-mediated cytotoxicity and transplantation immunity to Leukemia-associated antigens.", "content": "H-2 dependency of T cell-mediated cytotoxicity and transplantation immunity to leukemia-associated antigens has been investigated. Through the use of a 20-hr 125IUdR release assay, it was found that the induction of T cell-mediated cytotoxicity against Friend virus-induced leukemias of different H-2 haplotype orgins could be produced by immunization with both syngeneic and allogeneic tumor cells; the effector cells that were generated by syngeneic immunization could also provide effective killing of allogeneic tumor cells, although the killing of allogeneic targets might require a longer incubation time (20 to 40 hr). Furthermore, in vivo transplantation immunity against Friend virus-induced leukemias also was induced by immunization with both syngeneic and allogeneic tumors and syngeneic immunization could induce specific protection against the challenge with a-logeneic tumor in x-irradiated hosts. These findings clearly indicate that, both at the sensitizing phase and effector phase of the immune response, there is no strict H-2 dependency for T cell-mediated cytotoxicity or in in vivo transplantation imunity to leukemia-associated antigens.", "contents": "Studies of H-2 restriction in cell-mediated cytotoxicity and transplantation immunity to Leukemia-associated antigens. H-2 dependency of T cell-mediated cytotoxicity and transplantation immunity to leukemia-associated antigens has been investigated. Through the use of a 20-hr 125IUdR release assay, it was found that the induction of T cell-mediated cytotoxicity against Friend virus-induced leukemias of different H-2 haplotype orgins could be produced by immunization with both syngeneic and allogeneic tumor cells; the effector cells that were generated by syngeneic immunization could also provide effective killing of allogeneic tumor cells, although the killing of allogeneic targets might require a longer incubation time (20 to 40 hr). Furthermore, in vivo transplantation immunity against Friend virus-induced leukemias also was induced by immunization with both syngeneic and allogeneic tumors and syngeneic immunization could induce specific protection against the challenge with a-logeneic tumor in x-irradiated hosts. These findings clearly indicate that, both at the sensitizing phase and effector phase of the immune response, there is no strict H-2 dependency for T cell-mediated cytotoxicity or in in vivo transplantation imunity to leukemia-associated antigens."}
{"id": "PMID:191535", "title": "Regulation of lipopolysaccharide-induced granulopoiesis and macrophage formation by spleen cells. I. Relationship between colony-stimulating factor release and lymphocyte activation in vitro.", "content": "Addition of bacterial lipopolysaccharide (LPS), a B cell mitogen, to mouse spleen cultures strongly stimulated production of colony-stimulating factor (CSF), the humoral regulator of granulopoiesis, and macrophage formation in vitro. Secretion of CSF from LPS-stimulated spleen cells coincided with cellualr DNA synthesis and cell transformation and both activities could be attributed to the lipid A moiety of the molecule. Different experimental approaches were used to study the relationship of CSF release and lymphocyte activation in response to LPS: a) modification of LPS with polymyxin B, an antibiotic bactericidal for most Gram-negative bacteria, caused a marked reduction in mitogenic activity, although the ability to induce CSF was not significantly altered; b)spleen cells from CBA/N mice, a mutant strain with an x-linked genetic defect in immunologic and mitogenic responses to polyclonal activators including LPS, showed diminished mitogeinc responses; however, high levels of CSF were produced; c) mitotic and DNA inhibitors (colchicine and cytosine arabinoside) did not affect CSF release although they completely inhibited mitogenicity. Thus, the spleen cell population participating in the process of LPS-induced CSF generation is probably a nondividing, terminally differentiated one without need for DNA synthesis. In addition, it was also shown that active RNA and protein synthesis are needed in this process.", "contents": "Regulation of lipopolysaccharide-induced granulopoiesis and macrophage formation by spleen cells. I. Relationship between colony-stimulating factor release and lymphocyte activation in vitro. Addition of bacterial lipopolysaccharide (LPS), a B cell mitogen, to mouse spleen cultures strongly stimulated production of colony-stimulating factor (CSF), the humoral regulator of granulopoiesis, and macrophage formation in vitro. Secretion of CSF from LPS-stimulated spleen cells coincided with cellualr DNA synthesis and cell transformation and both activities could be attributed to the lipid A moiety of the molecule. Different experimental approaches were used to study the relationship of CSF release and lymphocyte activation in response to LPS: a) modification of LPS with polymyxin B, an antibiotic bactericidal for most Gram-negative bacteria, caused a marked reduction in mitogenic activity, although the ability to induce CSF was not significantly altered; b)spleen cells from CBA/N mice, a mutant strain with an x-linked genetic defect in immunologic and mitogenic responses to polyclonal activators including LPS, showed diminished mitogeinc responses; however, high levels of CSF were produced; c) mitotic and DNA inhibitors (colchicine and cytosine arabinoside) did not affect CSF release although they completely inhibited mitogenicity. Thus, the spleen cell population participating in the process of LPS-induced CSF generation is probably a nondividing, terminally differentiated one without need for DNA synthesis. In addition, it was also shown that active RNA and protein synthesis are needed in this process."}
{"id": "PMID:191536", "title": "Quantitation of antibody-complement mediated lysis of tumor cells.", "content": "An assay for quantitating antibody-complement mediated killing based on the release of 125I from 125IUdR labelled target cell is described. The temporal delay between antibody--complement damage and the release of nuclear material was shortened by treatment of the cells with a combination of trypsin and DNase. This treatment increased the rate of release of the labelled nuclear material from damaged cells without causing labelled nuclear material to be released from undamaged cells. The low level of spontaneous release of 125I from the target cells allows this assay to be used for experiments carried out over long time periods or in experiments involving extensive manipulations of the cells.", "contents": "Quantitation of antibody-complement mediated lysis of tumor cells. An assay for quantitating antibody-complement mediated killing based on the release of 125I from 125IUdR labelled target cell is described. The temporal delay between antibody--complement damage and the release of nuclear material was shortened by treatment of the cells with a combination of trypsin and DNase. This treatment increased the rate of release of the labelled nuclear material from damaged cells without causing labelled nuclear material to be released from undamaged cells. The low level of spontaneous release of 125I from the target cells allows this assay to be used for experiments carried out over long time periods or in experiments involving extensive manipulations of the cells."}
{"id": "PMID:191537", "title": "Prostaglandin biosynthesis in the epidermis and dermis of young mouse skin, and the effects of calcium and cyclic nucleotides.", "content": "Homogenates of skin from 2- to 3-day old mice converted labeled eicosa-8,11,14-trienoic acid to prostaglandins (PGs) PGE1, D1, and F1alpha. For several reasons PGD2 has been overlooked as a possible major PG in skin. The relative formation of each PG was modified by the presence of reduced glutathione (GSH), chelating agents (EDTA, EGTA), and L-epinephrine. Chelating agents and l-epinephrine increased conversion, espeicially to PGE1 but this effect was not due to inactivation of Ca++ which was shown to have no control over the reaction. Cyclic nucleotides including cyclic AMP (cAMP) and cyclic GMP (cGMP) were also ineffective. The conversion occurred mostly in the epidermis. Epidermal preparations were more efficient in the conversion than those from whole skin. Indomethacin (0.2 mM) completely inhibited the reaction.", "contents": "Prostaglandin biosynthesis in the epidermis and dermis of young mouse skin, and the effects of calcium and cyclic nucleotides. Homogenates of skin from 2- to 3-day old mice converted labeled eicosa-8,11,14-trienoic acid to prostaglandins (PGs) PGE1, D1, and F1alpha. For several reasons PGD2 has been overlooked as a possible major PG in skin. The relative formation of each PG was modified by the presence of reduced glutathione (GSH), chelating agents (EDTA, EGTA), and L-epinephrine. Chelating agents and l-epinephrine increased conversion, espeicially to PGE1 but this effect was not due to inactivation of Ca++ which was shown to have no control over the reaction. Cyclic nucleotides including cyclic AMP (cAMP) and cyclic GMP (cGMP) were also ineffective. The conversion occurred mostly in the epidermis. Epidermal preparations were more efficient in the conversion than those from whole skin. Indomethacin (0.2 mM) completely inhibited the reaction."}
{"id": "PMID:191538", "title": "Outbreak of pox disease among carnivora (felidae) and edentata.", "content": "An outbreak of pox disease in Carnivora of the family Felidae occurred in the Moscow Zoo. Two forms of the disease were found: (1) fatal, fulminant pulmonary without skin lesions and (2) dermal with rash. The severity of the dermal form varied from subclinical to lethal. The pulmonary form was characterized by pneumonia and exudative pleuritis, and large concentrations of virus were observed in the lungs and exudate. In addition to Carnivora of the family Felidae, two giant anteaters had a severe form of the disease (dermal with hemorrhages) and died. The agent of the outbreak appeared to be very closely related to cowpox virus; however, pocks developed at a lower temperature than do those that result from infection with cowpox virus. Strains isolated from sick animals were identical to the virus previously isolated from an outbreak of pox among elephants and okapi. The most probable sources of infection were rats that were fed to some of the animals. During the outbreak, a female attendant at the zoo became infected.", "contents": "Outbreak of pox disease among carnivora (felidae) and edentata. An outbreak of pox disease in Carnivora of the family Felidae occurred in the Moscow Zoo. Two forms of the disease were found: (1) fatal, fulminant pulmonary without skin lesions and (2) dermal with rash. The severity of the dermal form varied from subclinical to lethal. The pulmonary form was characterized by pneumonia and exudative pleuritis, and large concentrations of virus were observed in the lungs and exudate. In addition to Carnivora of the family Felidae, two giant anteaters had a severe form of the disease (dermal with hemorrhages) and died. The agent of the outbreak appeared to be very closely related to cowpox virus; however, pocks developed at a lower temperature than do those that result from infection with cowpox virus. Strains isolated from sick animals were identical to the virus previously isolated from an outbreak of pox among elephants and okapi. The most probable sources of infection were rats that were fed to some of the animals. During the outbreak, a female attendant at the zoo became infected."}
{"id": "PMID:191539", "title": "Jun\u00edn virus infection of guinea pigs: electron microscopic studies of peripheral blood and bone marrow.", "content": "Thin sections of peripheral white blood cells and samples of bone marrow from guinea pigs infected with Jun\u00edn virus were examined by electron microscopy. In peripheral blood cells, 40% of the granulocytes showed cytoplasmic lysis seven days after viral infection. After day 11 up to 80% of these cells showed morphological alterations. However, no intra- or extracellular viral particles were detected in these samples. Microscopy of bone marrow preparations revealed that 10% of the cells were altered five days after infection, and approximately 50% were affected after nine days. At this stage the megakaryocyte channels were seen to contain pleomorphic particles with a mean diameter of 80-100 nm. These particles had a unit membrane envelope and internal dense granules similar to those observed during other arenavirus infections. Therefore, it is suggested that the effect of Jun\u00edn virus upon megakaryocytes may be a factor responsible for the acute thrombocytopenia observed in Argentine hemorrhagic fever.", "contents": "Jun\u00edn virus infection of guinea pigs: electron microscopic studies of peripheral blood and bone marrow. Thin sections of peripheral white blood cells and samples of bone marrow from guinea pigs infected with Jun\u00edn virus were examined by electron microscopy. In peripheral blood cells, 40% of the granulocytes showed cytoplasmic lysis seven days after viral infection. After day 11 up to 80% of these cells showed morphological alterations. However, no intra- or extracellular viral particles were detected in these samples. Microscopy of bone marrow preparations revealed that 10% of the cells were altered five days after infection, and approximately 50% were affected after nine days. At this stage the megakaryocyte channels were seen to contain pleomorphic particles with a mean diameter of 80-100 nm. These particles had a unit membrane envelope and internal dense granules similar to those observed during other arenavirus infections. Therefore, it is suggested that the effect of Jun\u00edn virus upon megakaryocytes may be a factor responsible for the acute thrombocytopenia observed in Argentine hemorrhagic fever."}
{"id": "PMID:191540", "title": "Endogenous reactivation of Epstein-Barr virus infections.", "content": "In a prior systematic community survey, 20 adults were found to have antibodies to viral capsid antigen (VCA) and early antigen (EA) OF Epstein-Barr virus (EBV) in serum. The presence of the latter antibody suggested a recent response to EBV. In the present study the significance of antibody to EA was more extensively evaluated by examination of the sera of these adults for the presence of EBV-specific IgM antibodies (EBV-IgM) and antibodies to EBV nuclear antigen (EBVNA). Sera of a matched group of adults with antibodies to VCA but without antibodies to EA were compared with those of the 20 adults with antibodies to EA (anti-EA-positive). In the anti-EA-positive group, 19 specimens of serum contained EBV-IgM, 16 contained elevated titers of antibodies to VCA, and 20 contained antibodies to EBVNA. The sera of the matched group had neither detectable EBV-IgM nor elevated titers of antibodies to VCA; however, all sera had antibodies to EBVNA. None of the individuals gave a history of an infectious mononucleosis-like illness. It was suggested that the majority, if not all, of the anti-EA-positive group were manifesting a host immune response to endogenous reactivation of latent EBV. It is of interest that the presence of EBV-IgM was part of this response.", "contents": "Endogenous reactivation of Epstein-Barr virus infections. In a prior systematic community survey, 20 adults were found to have antibodies to viral capsid antigen (VCA) and early antigen (EA) OF Epstein-Barr virus (EBV) in serum. The presence of the latter antibody suggested a recent response to EBV. In the present study the significance of antibody to EA was more extensively evaluated by examination of the sera of these adults for the presence of EBV-specific IgM antibodies (EBV-IgM) and antibodies to EBV nuclear antigen (EBVNA). Sera of a matched group of adults with antibodies to VCA but without antibodies to EA were compared with those of the 20 adults with antibodies to EA (anti-EA-positive). In the anti-EA-positive group, 19 specimens of serum contained EBV-IgM, 16 contained elevated titers of antibodies to VCA, and 20 contained antibodies to EBVNA. The sera of the matched group had neither detectable EBV-IgM nor elevated titers of antibodies to VCA; however, all sera had antibodies to EBVNA. None of the individuals gave a history of an infectious mononucleosis-like illness. It was suggested that the majority, if not all, of the anti-EA-positive group were manifesting a host immune response to endogenous reactivation of latent EBV. It is of interest that the presence of EBV-IgM was part of this response."}
{"id": "PMID:191541", "title": "Specific impairment of cell-mediated immunity in mothers of infants with congenital infection due to cytomegalovirus.", "content": "Specific lymphocyte-mediated cytotoxicity to cytomegalovirus (CMV) in eight infants (six to 27 months old) with congenital CMV infection and in the mothers of six of these infants was evaluated with use of a 51chromium (51Cr)-release microassay. The control population consisted of 25 normal newborns, children, and adults. The titers of indirect hemagglutinating (IHA) antibody to CMV in the infected infants ranged from 1:16 to 1:1,024. All of these infants had detectable specific immune release of 51Cr that ranged from 3.3% to 48.9% (mean +/-SE, 21.0%+/-5.6%). The mothers of these infants demonstrated significantly elevated titers of IHA antibody to CMV (geometric mean titer, 1:410) as compared with a mean titer of 1:22 in controls (t = 5.71; P less than 0.001) but showed significantly depressed specific immune release (9.2% +/- 3.2%) compared with that of normal seropositive controls (24.8% +/- 2.8%; t = 3.31; P less than 0.001). In addition, two adult nulliparous women with persistent CMV viruria were also found to have depressed specific immune release to CMV (10.8% and 16.2%). These data suggest that a specific impairment in cell-mediated immunity to CMV occurs in mothers of infants with congenital CMV infection and in some persons who persistently excrete CMV.", "contents": "Specific impairment of cell-mediated immunity in mothers of infants with congenital infection due to cytomegalovirus. Specific lymphocyte-mediated cytotoxicity to cytomegalovirus (CMV) in eight infants (six to 27 months old) with congenital CMV infection and in the mothers of six of these infants was evaluated with use of a 51chromium (51Cr)-release microassay. The control population consisted of 25 normal newborns, children, and adults. The titers of indirect hemagglutinating (IHA) antibody to CMV in the infected infants ranged from 1:16 to 1:1,024. All of these infants had detectable specific immune release of 51Cr that ranged from 3.3% to 48.9% (mean +/-SE, 21.0%+/-5.6%). The mothers of these infants demonstrated significantly elevated titers of IHA antibody to CMV (geometric mean titer, 1:410) as compared with a mean titer of 1:22 in controls (t = 5.71; P less than 0.001) but showed significantly depressed specific immune release (9.2% +/- 3.2%) compared with that of normal seropositive controls (24.8% +/- 2.8%; t = 3.31; P less than 0.001). In addition, two adult nulliparous women with persistent CMV viruria were also found to have depressed specific immune release to CMV (10.8% and 16.2%). These data suggest that a specific impairment in cell-mediated immunity to CMV occurs in mothers of infants with congenital CMV infection and in some persons who persistently excrete CMV."}
{"id": "PMID:191542", "title": "Effect of adenine arabinoside on Epstein-Barr virus in vitro.", "content": "The effect of adenine arabinoside (ara-A) on Epstein-Barr virus (EBV) in cultures of lymphoid cells was examined with use of an EBV-producing cell line, P3HR-1, and a nonproducing cell line, Raji. The presence of EBV-associated viral capsid antigen (VCA) and early antigen (EA) was detected by indirect immunofluorescence. Ara-A inhibited the expression of VCA in P3HR-1 cells at concentrations fivefold below those that inhibited cell multiplication; there was no concomitant accumulation of EA. Ara-A did not inhibit superinfection of Raji cells with EBV and did not induce EA until high concentrations of the compound were reached. The inhibition of the expression of VCA but not EA is consistent with a postulated inhibition by ara-A of viral-directed synthesis of DNA. At low concentrations, ara-A may exert a more specific antiviral effect than that reported for idoxuridine and cytosine arabinoside in this system.", "contents": "Effect of adenine arabinoside on Epstein-Barr virus in vitro. The effect of adenine arabinoside (ara-A) on Epstein-Barr virus (EBV) in cultures of lymphoid cells was examined with use of an EBV-producing cell line, P3HR-1, and a nonproducing cell line, Raji. The presence of EBV-associated viral capsid antigen (VCA) and early antigen (EA) was detected by indirect immunofluorescence. Ara-A inhibited the expression of VCA in P3HR-1 cells at concentrations fivefold below those that inhibited cell multiplication; there was no concomitant accumulation of EA. Ara-A did not inhibit superinfection of Raji cells with EBV and did not induce EA until high concentrations of the compound were reached. The inhibition of the expression of VCA but not EA is consistent with a postulated inhibition by ara-A of viral-directed synthesis of DNA. At low concentrations, ara-A may exert a more specific antiviral effect than that reported for idoxuridine and cytosine arabinoside in this system."}
{"id": "PMID:191543", "title": "Interaction of adenine arabinoside and host defense factors in experimental infections due to Herpesvirus hominis.", "content": "The role of host immune functions in relation to the antiviral effects of adenine arabinoside (ara-A) and/or humoral antibodies in Herpesvirus hominis infection was studied in four different mouse models (newborn Swiss mice, three-week-old Swiss mice, athymic nude [nu/nu] mice, and phenotypically normal [nu/+] littermates of nude mice). Although the overall beneficial effects afforded by the administration of ara-A and/or humoral antibodies were similar, the degree of protection varied among the four host systems. The data indicate that host defense factors play an important role in modulating the effect of humoral antibodies and/or an antiviral agent. Combined use of ara-A and humoral antibodies resulted in enhanced protection against H. hominis infection. Our data suggest that control of viral infection, particularly in compromised hosts, may require chemoimmunotherapy.", "contents": "Interaction of adenine arabinoside and host defense factors in experimental infections due to Herpesvirus hominis. The role of host immune functions in relation to the antiviral effects of adenine arabinoside (ara-A) and/or humoral antibodies in Herpesvirus hominis infection was studied in four different mouse models (newborn Swiss mice, three-week-old Swiss mice, athymic nude [nu/nu] mice, and phenotypically normal [nu/+] littermates of nude mice). Although the overall beneficial effects afforded by the administration of ara-A and/or humoral antibodies were similar, the degree of protection varied among the four host systems. The data indicate that host defense factors play an important role in modulating the effect of humoral antibodies and/or an antiviral agent. Combined use of ara-A and humoral antibodies resulted in enhanced protection against H. hominis infection. Our data suggest that control of viral infection, particularly in compromised hosts, may require chemoimmunotherapy."}
{"id": "PMID:191544", "title": "Progressive inhibition of T-cell function preceding clinical signs of cytomegalovirus infection in mice.", "content": "Groups of mice that received a predominantly lethal or a nonlethal dose of murine cytomegalovirus (CMV) were studied prospectively to correlate clinical observations with detection of virus in spleen cells and with the response of spleen cells to the thymus-derived (T-) cell mitogen concanavalin A (con A). In both groups of mice, virus was virtually cleared from spleen cells by day 8 after infection. Depression of the spleen cell response to con A preceded clinical signs of infection, was more severe in the lethally infected group, and improved as clinical signs cleared in the few surviving mice. Serum from infected mice depressed the response of uninfected spleen cells to con A. These findings support the hypothesis that clinical illness and death from CMV infection of mice are a consequence of events that follow the depression of T-cell function by CMV. This depression is at least partially mediated by a humoral mechanism.", "contents": "Progressive inhibition of T-cell function preceding clinical signs of cytomegalovirus infection in mice. Groups of mice that received a predominantly lethal or a nonlethal dose of murine cytomegalovirus (CMV) were studied prospectively to correlate clinical observations with detection of virus in spleen cells and with the response of spleen cells to the thymus-derived (T-) cell mitogen concanavalin A (con A). In both groups of mice, virus was virtually cleared from spleen cells by day 8 after infection. Depression of the spleen cell response to con A preceded clinical signs of infection, was more severe in the lethally infected group, and improved as clinical signs cleared in the few surviving mice. Serum from infected mice depressed the response of uninfected spleen cells to con A. These findings support the hypothesis that clinical illness and death from CMV infection of mice are a consequence of events that follow the depression of T-cell function by CMV. This depression is at least partially mediated by a humoral mechanism."}
{"id": "PMID:191545", "title": "Herpes simplex virus types 1 and 2 in clinical infections: differences observed by electron microscopy.", "content": "Microtubule-like structures have been observed ultrastructurally in BHK-21/4 cells infected with herpes simplex virus type 2 (HSV-2) but not in cells infected with herpes simplex virus type 1 (HSV-1). BHK-21/4 cells were infected with two known strains of HSV-2 and one known strain of HSV-1, as well as with vesicular fluid from 50 clinical isolates (47 perioral, two penile, and one from the leg) in an examination of the accuracy of electron microscopy for differentiation between clinical isolates of HSV-1 and HSV-2. Cells infected with the known strains of HSV-2 or with material from the genital or leg lesions demonstrated microtubule-like structures. Cells infected by a known strain of HSV-1 or by material from perioral lesions did not show evidence of microtubule-like structures. Typing by indirect hemagglutination of these same 50 clinical isolates gave identical results.", "contents": "Herpes simplex virus types 1 and 2 in clinical infections: differences observed by electron microscopy. Microtubule-like structures have been observed ultrastructurally in BHK-21/4 cells infected with herpes simplex virus type 2 (HSV-2) but not in cells infected with herpes simplex virus type 1 (HSV-1). BHK-21/4 cells were infected with two known strains of HSV-2 and one known strain of HSV-1, as well as with vesicular fluid from 50 clinical isolates (47 perioral, two penile, and one from the leg) in an examination of the accuracy of electron microscopy for differentiation between clinical isolates of HSV-1 and HSV-2. Cells infected with the known strains of HSV-2 or with material from the genital or leg lesions demonstrated microtubule-like structures. Cells infected by a known strain of HSV-1 or by material from perioral lesions did not show evidence of microtubule-like structures. Typing by indirect hemagglutination of these same 50 clinical isolates gave identical results."}
{"id": "PMID:191546", "title": "Inhibitory and lethal concentrations of 9-beta-D-arabinofuranosyladenine and its hypoxanthine-derivative versus herpes simplex virus, type 1.", "content": "Minimum inhibitory concentrations of 9-beta-D-arabinofuranosyladenine (ara-A, adenine arabinoside, vidarabine) and a purified preparation of 9-beta-D-arabinofuranosylhypoxanthine (arabinoslhypoxanthine, ara-Hx) at end points of 50% MIC50) and 100% (MIC100) reduction to challenges of approximately 50 p.f.u. of herpes simplex virus, type 1 (HSV-1) were determined in vero renal tissue cultures. Adenosine deaminase is universally present in tissue cultures and serum. These same tests were repeated in the presence of a potent inhibitor of adenosine deaminase, R-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo-4,5-d)-(1,3)-diazepin-8-ol (co-vidarabine, co-ara-A). Addition of co-ara-A to assays of MIC50 or MIC100 for ara-A ensures standard reproducible results which can be compared in different laboratories. After incubations of HSV-1 in infected cultures for 96 hours, 35 degrees C., with concentrations of ara-A or ara-Hx at the MIC100 and over, cells were scraped and sonicated. Supernates were then reinoculated into vero flasks free of antiviral agents to determine minimum lethal concentrations (MLC's). Standard values (microng/ml.) for ara-A with co-ara-A are 11.3 (MIC50), 17.0 (MIC100), and 34.0 (MLC) but are 68.1 (MIC50), 170.4 (MIC100) and 375 (MLC) for ara-Hx. These data confirm that as a virustatic agent (MIC100) ara-A is 10 times more active than ara-Hx. Ara-A and ara-Hx have virucidal potentials which require approximately two times the respective MIC100.", "contents": "Inhibitory and lethal concentrations of 9-beta-D-arabinofuranosyladenine and its hypoxanthine-derivative versus herpes simplex virus, type 1. Minimum inhibitory concentrations of 9-beta-D-arabinofuranosyladenine (ara-A, adenine arabinoside, vidarabine) and a purified preparation of 9-beta-D-arabinofuranosylhypoxanthine (arabinoslhypoxanthine, ara-Hx) at end points of 50% MIC50) and 100% (MIC100) reduction to challenges of approximately 50 p.f.u. of herpes simplex virus, type 1 (HSV-1) were determined in vero renal tissue cultures. Adenosine deaminase is universally present in tissue cultures and serum. These same tests were repeated in the presence of a potent inhibitor of adenosine deaminase, R-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo-4,5-d)-(1,3)-diazepin-8-ol (co-vidarabine, co-ara-A). Addition of co-ara-A to assays of MIC50 or MIC100 for ara-A ensures standard reproducible results which can be compared in different laboratories. After incubations of HSV-1 in infected cultures for 96 hours, 35 degrees C., with concentrations of ara-A or ara-Hx at the MIC100 and over, cells were scraped and sonicated. Supernates were then reinoculated into vero flasks free of antiviral agents to determine minimum lethal concentrations (MLC's). Standard values (microng/ml.) for ara-A with co-ara-A are 11.3 (MIC50), 17.0 (MIC100), and 34.0 (MLC) but are 68.1 (MIC50), 170.4 (MIC100) and 375 (MLC) for ara-Hx. These data confirm that as a virustatic agent (MIC100) ara-A is 10 times more active than ara-Hx. Ara-A and ara-Hx have virucidal potentials which require approximately two times the respective MIC100."}
{"id": "PMID:191547", "title": "Calcium pyrophosphate dihydrate (CPPD) crystal-induced chemotactic factor: subcellular localization, role of protein synthesis and phagocytosis.", "content": "A factor with chemotactic properties for polymorphonuclear leukocytes appears in their lysosomal fraction following phagocytosis of CCPD crystals. The factor, whose appearance was blocked by inhibition of protein synthesis, was estimated to have a molecular weight of 8,400 daltons. Inhibition of crystal phagocytosis by cytochalasin B was also shown to inhibit the generation of chemotactic factor activity, indicating that ingestion of the crystals by the cell is essential for the generation of the CPPD crystal-induced chemotactic factor. This latter finding provides a clue in the understanding of the development and termination of the acute pseudogout attack.", "contents": "Calcium pyrophosphate dihydrate (CPPD) crystal-induced chemotactic factor: subcellular localization, role of protein synthesis and phagocytosis. A factor with chemotactic properties for polymorphonuclear leukocytes appears in their lysosomal fraction following phagocytosis of CCPD crystals. The factor, whose appearance was blocked by inhibition of protein synthesis, was estimated to have a molecular weight of 8,400 daltons. Inhibition of crystal phagocytosis by cytochalasin B was also shown to inhibit the generation of chemotactic factor activity, indicating that ingestion of the crystals by the cell is essential for the generation of the CPPD crystal-induced chemotactic factor. This latter finding provides a clue in the understanding of the development and termination of the acute pseudogout attack."}
{"id": "PMID:191548", "title": "Interaction of cholesterol ester and triglyceride in human plasma very low density lipoprotein.", "content": "The properties of human plasma very low density lipoproteins (VLDL), low density lipoproteins (LDL), and their extracted lipids were compared using calorimetric, X-ray scattering, and polarizing microscopy techniques. Intact LDL, and cholesterol esters isolated from LDL and VLDL each undergo reversible changes in their physical state around body temperature. These transitions are associated with ordered liquid crystalline to liquid phase changes of the cholesterol esters. In contrast to LDL, VLDL has no reversible transitions and shows no evidence of ordered liquid crystalline structures between 10 and 45 degrees C. Therefore, unlike LDL, VLDL does not contain a separate cholesterol ester region capable of undergoing cooperative melting. Solubility studies at 37 degrees C of cholesterol esters and triglyceride isolated from VLDL show that even at a weight ratio of 1:1, which greatly exceeds the relative amount of cholesterol esters in VLDL, cholesterol ester is completely soluble in triglyceride. Thus, the cholesterol ester in VLDL is not sequestered in a separate domain within VLDL, but is dissolved in the liquid core of the particle.", "contents": "Interaction of cholesterol ester and triglyceride in human plasma very low density lipoprotein. The properties of human plasma very low density lipoproteins (VLDL), low density lipoproteins (LDL), and their extracted lipids were compared using calorimetric, X-ray scattering, and polarizing microscopy techniques. Intact LDL, and cholesterol esters isolated from LDL and VLDL each undergo reversible changes in their physical state around body temperature. These transitions are associated with ordered liquid crystalline to liquid phase changes of the cholesterol esters. In contrast to LDL, VLDL has no reversible transitions and shows no evidence of ordered liquid crystalline structures between 10 and 45 degrees C. Therefore, unlike LDL, VLDL does not contain a separate cholesterol ester region capable of undergoing cooperative melting. Solubility studies at 37 degrees C of cholesterol esters and triglyceride isolated from VLDL show that even at a weight ratio of 1:1, which greatly exceeds the relative amount of cholesterol esters in VLDL, cholesterol ester is completely soluble in triglyceride. Thus, the cholesterol ester in VLDL is not sequestered in a separate domain within VLDL, but is dissolved in the liquid core of the particle."}
{"id": "PMID:191549", "title": "Chylomicron remnant cholesteryl esters as the major constituent of very low density lipoproteins in plasma of cholesterol-fed rabbits.", "content": "Feeding rabbits 500 mg of cholesterol daily for 4 to 15 days greatly increased the concentration of esterified cholesterol in lipoproteins of d less than 1.006 g/ml. The origin of hypercholesterolemic very low density lipoproteins was investigated by monitoring the degradation of labeled lymph chyomicrons administered to normal and cholesterol-fed rabbits. Chylomicrons were labeled in vivo by feeding either 1) [3H]cholesterol and [14C]oleic acid or 2) [14C]cholesterol and [3H]retinyl acetate. After intravenous injection of labeled chylomicrons to recipient rabbits, [14C]triglyceride hydrolysis was equally rapid in normal and cholesterol-fed animals. Normal rabbits rapidly removed from plasma both labeled cholesteryl and retinyl esters, whereas cholesterol-fed rabbits retained nearly 50% of doubly labeled remnants in plasma 25 min after chylomicron injection. Ultracentrifugal separation of plasma into subfractions of very low density lipoproteins showed that chylomicron remnants in cholesterol-fed animals are found among all subclasses of very low density lipoproteins. Analysis of cholesteryl ester specific activity-time curves for the very low density lipoproteins subfraction from hypercholesterolemic plasma showed that nearly all esterified cholesterol in large very low density lipoproteins and approximately 30% of esterified cholesterol in small very low density lipoproteins was derived from chylomicron degradation. Apparently, nearly two-thirds of the esterified cholesterol in total very low density lipoproteins from moderately hypercholesterolemic rabbits is of dietary origin.", "contents": "Chylomicron remnant cholesteryl esters as the major constituent of very low density lipoproteins in plasma of cholesterol-fed rabbits. Feeding rabbits 500 mg of cholesterol daily for 4 to 15 days greatly increased the concentration of esterified cholesterol in lipoproteins of d less than 1.006 g/ml. The origin of hypercholesterolemic very low density lipoproteins was investigated by monitoring the degradation of labeled lymph chyomicrons administered to normal and cholesterol-fed rabbits. Chylomicrons were labeled in vivo by feeding either 1) [3H]cholesterol and [14C]oleic acid or 2) [14C]cholesterol and [3H]retinyl acetate. After intravenous injection of labeled chylomicrons to recipient rabbits, [14C]triglyceride hydrolysis was equally rapid in normal and cholesterol-fed animals. Normal rabbits rapidly removed from plasma both labeled cholesteryl and retinyl esters, whereas cholesterol-fed rabbits retained nearly 50% of doubly labeled remnants in plasma 25 min after chylomicron injection. Ultracentrifugal separation of plasma into subfractions of very low density lipoproteins showed that chylomicron remnants in cholesterol-fed animals are found among all subclasses of very low density lipoproteins. Analysis of cholesteryl ester specific activity-time curves for the very low density lipoproteins subfraction from hypercholesterolemic plasma showed that nearly all esterified cholesterol in large very low density lipoproteins and approximately 30% of esterified cholesterol in small very low density lipoproteins was derived from chylomicron degradation. Apparently, nearly two-thirds of the esterified cholesterol in total very low density lipoproteins from moderately hypercholesterolemic rabbits is of dietary origin."}
{"id": "PMID:191550", "title": "Influence of dietary trans-fatty acids on swine lipoprotein composition and structure.", "content": "Four groups of 20 weanling swine each were fed either (a) basal diet, (b) basal plus hydrogenated fat (13% trans), (c) basal plus hydrogenated fat (13% trans) and 0.4% cholesterol, or (d) basal plus beef tallow (all cis). After six months of feeding, the animals were killed and the blood and aortas were removed. Very low density, low density, and high density lipoproteins were then isolated from the plasma by ultracentrifugal flotation. Although the fatty acid composition of the basal diet was different from the diets supplemented with either hydrogenated fat containing trans-fatty acid or beef tallow containing all cis, the lipid and fatty acid compositions of each of the isolated lipoprotein classes for the four groups of animals were remarkably similar. Elaidate was clearly incorporated into the lipoproteins of animals fed hydrogenated fat, but the level of incorporation was generally less than 5%. In a direct comparison of the structure of the lipoproteins from the different groups, we did not find any significant differences in their physical properties as determined by pyrene fluorescence and electron paramagnetic resonance methods. Grossly visible fatty streaks and fibrous plaques were not found in any of the swine aorta. However, light and electron microscopy indicated the presence of atherosclerotic lesions in the distal abdominal aorta and bifurcation. These studies demonstrate that a diet containing a substantial amount of trans-fatty acid leads to a small but definite incorporation into the swine lipoproteins. However, such changes had relatively little effect on lipoprotein structure or the presence of atherosclerotic lesions in these 6-month-old swine.", "contents": "Influence of dietary trans-fatty acids on swine lipoprotein composition and structure. Four groups of 20 weanling swine each were fed either (a) basal diet, (b) basal plus hydrogenated fat (13% trans), (c) basal plus hydrogenated fat (13% trans) and 0.4% cholesterol, or (d) basal plus beef tallow (all cis). After six months of feeding, the animals were killed and the blood and aortas were removed. Very low density, low density, and high density lipoproteins were then isolated from the plasma by ultracentrifugal flotation. Although the fatty acid composition of the basal diet was different from the diets supplemented with either hydrogenated fat containing trans-fatty acid or beef tallow containing all cis, the lipid and fatty acid compositions of each of the isolated lipoprotein classes for the four groups of animals were remarkably similar. Elaidate was clearly incorporated into the lipoproteins of animals fed hydrogenated fat, but the level of incorporation was generally less than 5%. In a direct comparison of the structure of the lipoproteins from the different groups, we did not find any significant differences in their physical properties as determined by pyrene fluorescence and electron paramagnetic resonance methods. Grossly visible fatty streaks and fibrous plaques were not found in any of the swine aorta. However, light and electron microscopy indicated the presence of atherosclerotic lesions in the distal abdominal aorta and bifurcation. These studies demonstrate that a diet containing a substantial amount of trans-fatty acid leads to a small but definite incorporation into the swine lipoproteins. However, such changes had relatively little effect on lipoprotein structure or the presence of atherosclerotic lesions in these 6-month-old swine."}
{"id": "PMID:191551", "title": "Characterization of plasma low density lipoproteins on nonhuman primates fed dietary cholesterol.", "content": "LDL from animals of three nonhuman primate species, Macaca mulatta, Macaca fascicularis, and Cercopithecus aethiops, were studied. A standard preparation of 125I-LDL was added to isolated lipoprotein mixtures just prior to separation of plasma lipoproteins by agarose gel chromatography. A relative size index, rI, was determined by dividing the elution volume of the iodinated LDL by the elution volume of the sample LDL, both volumes being determined simultaneously during chromatographic elution. Comparison of rI with molecular weights measured by flotation equilibrium analysis in the analytical ultracentrifuge showed a linear relationship across a molecular weight range of 2.5-8.0 X 10(6), r = 0.985. A regression equation describing this relationship was used to calculate molecular weights of LDL from a group of M. fascicularis that were fed cholesterol-containing diets. In these animals, plasma cholesterol concentration ranged from 100 to over 700 mg/dl and was highly correlated with LDL molecular weight and with the micromolar concentration of the LDL. Using multiple regression analyses, the two variables of plasma LDL could be shown to account for 94% of the variation in plasma cholesterol concentration in the M. fascicularis of this study. Micromolar concentration and molecular weight of LDL were not correlated with each other, suggesting that in M. fascicularis at least two independent types of controls are operative in the response of plasma LDL to dietary cholesterol. The increase in LDL molecular weight was associated with a large increase in cholesteryl ester content and concomitant smaller increases in protein, phospholipid, and free cholesterol. As molecular weight increased, these components appeared to be added to the LDL particles together as discrete increments of fixed composition. The data are consistent with a spherical model of LDL structure with a core of cholesteryl ester and triglyceride and a 21.3 A-thick coat of phospholipid, free cholesterol, and protein.", "contents": "Characterization of plasma low density lipoproteins on nonhuman primates fed dietary cholesterol. LDL from animals of three nonhuman primate species, Macaca mulatta, Macaca fascicularis, and Cercopithecus aethiops, were studied. A standard preparation of 125I-LDL was added to isolated lipoprotein mixtures just prior to separation of plasma lipoproteins by agarose gel chromatography. A relative size index, rI, was determined by dividing the elution volume of the iodinated LDL by the elution volume of the sample LDL, both volumes being determined simultaneously during chromatographic elution. Comparison of rI with molecular weights measured by flotation equilibrium analysis in the analytical ultracentrifuge showed a linear relationship across a molecular weight range of 2.5-8.0 X 10(6), r = 0.985. A regression equation describing this relationship was used to calculate molecular weights of LDL from a group of M. fascicularis that were fed cholesterol-containing diets. In these animals, plasma cholesterol concentration ranged from 100 to over 700 mg/dl and was highly correlated with LDL molecular weight and with the micromolar concentration of the LDL. Using multiple regression analyses, the two variables of plasma LDL could be shown to account for 94% of the variation in plasma cholesterol concentration in the M. fascicularis of this study. Micromolar concentration and molecular weight of LDL were not correlated with each other, suggesting that in M. fascicularis at least two independent types of controls are operative in the response of plasma LDL to dietary cholesterol. The increase in LDL molecular weight was associated with a large increase in cholesteryl ester content and concomitant smaller increases in protein, phospholipid, and free cholesterol. As molecular weight increased, these components appeared to be added to the LDL particles together as discrete increments of fixed composition. The data are consistent with a spherical model of LDL structure with a core of cholesteryl ester and triglyceride and a 21.3 A-thick coat of phospholipid, free cholesterol, and protein."}
{"id": "PMID:191552", "title": "Microdetermination of cholesterol in serum lipoproteins.", "content": "A two-step procedure for the microdetermination of cholesterol in serum lipoproteins is compared with cholesterol quantitation after density gradient ultracentrifugation. Serum lipoproteins from 10 mul of serum are separated by electrophoresis on agarose and visualized by precipitation with dextran sulfate--CaCl2. The lipoprotein bands are cut off from the plates, the agarose slices are hydrolyzed by gas-liquid chromatography. The comparison between the two procedures reveals satisfactory correlations for beta-and pre-beta-lipoproteins and total serum. There is excellent recovery of cholesterol in fractionated lipoproteins.", "contents": "Microdetermination of cholesterol in serum lipoproteins. A two-step procedure for the microdetermination of cholesterol in serum lipoproteins is compared with cholesterol quantitation after density gradient ultracentrifugation. Serum lipoproteins from 10 mul of serum are separated by electrophoresis on agarose and visualized by precipitation with dextran sulfate--CaCl2. The lipoprotein bands are cut off from the plates, the agarose slices are hydrolyzed by gas-liquid chromatography. The comparison between the two procedures reveals satisfactory correlations for beta-and pre-beta-lipoproteins and total serum. There is excellent recovery of cholesterol in fractionated lipoproteins."}
{"id": "PMID:191553", "title": "Restricted mandibular movement. Report of 2 unusual causes.", "content": "Hypomobility of the temporomandibular joint has a variety of causes. Two patients are presented in whom restricted jaw movement was the only clinical manifestation of serious underlying disease. The importance of submitting all tissues removed from patients for histopathological diagnosis is stressed.", "contents": "Restricted mandibular movement. Report of 2 unusual causes. Hypomobility of the temporomandibular joint has a variety of causes. Two patients are presented in whom restricted jaw movement was the only clinical manifestation of serious underlying disease. The importance of submitting all tissues removed from patients for histopathological diagnosis is stressed."}
{"id": "PMID:191554", "title": "Signal propagation in 2-dimensional threshold cellular space.", "content": "A two-dimensional network of uniformly connected McCulloch-Pitts neurons is considered and signal propagations in the network are analyzed. The problems are set up in the framework of cellular space such that each cell is a copy of any given McCulloch-Pitts neuron and is connected to the nearest neighboring cells. It is assumed that the threshold value is positive and that there exists only one firing cell at the beginning. Then it is shown that essentially there are only four signal propagation patterns and a firing pattern at any time t can be obtained by such a superposition of the propagation patterns that includes the newly defined concept of dominance and assimilation. The exact formulae representing firing patterns at any time t are obtained for any finite rectangle cell space with constant 0 (i.e., non-firing) boundary condition and for the entire two-dimensional cellular space.", "contents": "Signal propagation in 2-dimensional threshold cellular space. A two-dimensional network of uniformly connected McCulloch-Pitts neurons is considered and signal propagations in the network are analyzed. The problems are set up in the framework of cellular space such that each cell is a copy of any given McCulloch-Pitts neuron and is connected to the nearest neighboring cells. It is assumed that the threshold value is positive and that there exists only one firing cell at the beginning. Then it is shown that essentially there are only four signal propagation patterns and a firing pattern at any time t can be obtained by such a superposition of the propagation patterns that includes the newly defined concept of dominance and assimilation. The exact formulae representing firing patterns at any time t are obtained for any finite rectangle cell space with constant 0 (i.e., non-firing) boundary condition and for the entire two-dimensional cellular space."}
{"id": "PMID:191556", "title": "Temporal relationships between the diurnal rhythm of hypothalamic corticotrophin releasing factor, pituitary corticotrophin and plasma corticosterone in the rat.", "content": "Plasma corticosterone (fluorometric assay), pituitary ACTH (bioassay using isolated adrenal cells) and hypothalamic corticotrophin releasing factor (CRF) (bioassay using isolated pituitary cells) were measured singly in groups of six female rats which were killed at 11.00, 15.00, 19.00, 21.00, 23.00, 01.00, 03.00, 05.00, 07.00 and 11.00 h, after 5 weeks of adaptation to a photoperiod of 12 h light: 12 h darkness. Locomotor activity was recorded continuously, using actographic cages, and the waking/sleep pattern was recorded by electroencephalography from chronically implanted control rats during the first hours of the light span. The three hormones msured fluctuated with a 24 h rhythmicity, with extreme values ranging between 4-12+/-1-42 and 31-78+/-194(S.E.M.) microng/100 ml for corticosterone, 4486+/-269 and 16629+/-882 micronu/mg pituitary for ACTH, and 439+/-20 and 1270+/-39 micronu. ACTH production/hypothalamus/10(5) pituitary cells. The onset of the ascending phase of the rhythm started during the first 2 h of light for CRF, 2 h later for ACTH, and again 2 h later for corticosterone. Similarly, the estimated acrophase of the rhythms occurred respectively, 9-4 (CRF), 10-3 (ACTH) and 14-4 h (corticosterone) after onset of light. These phase relationships point to a central origin of the adrenal rhythm. The diurnal activation of CRF at the very beginning of the light phase was concomitant with an almost immediate reduction of the locomotor activity and onset of sleep. These correlations favour the hypothesis of a common temporal control of both the adrenal and the sleep/waking rhythms.", "contents": "Temporal relationships between the diurnal rhythm of hypothalamic corticotrophin releasing factor, pituitary corticotrophin and plasma corticosterone in the rat. Plasma corticosterone (fluorometric assay), pituitary ACTH (bioassay using isolated adrenal cells) and hypothalamic corticotrophin releasing factor (CRF) (bioassay using isolated pituitary cells) were measured singly in groups of six female rats which were killed at 11.00, 15.00, 19.00, 21.00, 23.00, 01.00, 03.00, 05.00, 07.00 and 11.00 h, after 5 weeks of adaptation to a photoperiod of 12 h light: 12 h darkness. Locomotor activity was recorded continuously, using actographic cages, and the waking/sleep pattern was recorded by electroencephalography from chronically implanted control rats during the first hours of the light span. The three hormones msured fluctuated with a 24 h rhythmicity, with extreme values ranging between 4-12+/-1-42 and 31-78+/-194(S.E.M.) microng/100 ml for corticosterone, 4486+/-269 and 16629+/-882 micronu/mg pituitary for ACTH, and 439+/-20 and 1270+/-39 micronu. ACTH production/hypothalamus/10(5) pituitary cells. The onset of the ascending phase of the rhythm started during the first 2 h of light for CRF, 2 h later for ACTH, and again 2 h later for corticosterone. Similarly, the estimated acrophase of the rhythms occurred respectively, 9-4 (CRF), 10-3 (ACTH) and 14-4 h (corticosterone) after onset of light. These phase relationships point to a central origin of the adrenal rhythm. The diurnal activation of CRF at the very beginning of the light phase was concomitant with an almost immediate reduction of the locomotor activity and onset of sleep. These correlations favour the hypothesis of a common temporal control of both the adrenal and the sleep/waking rhythms."}
{"id": "PMID:191557", "title": "The use of corticotrophin production by adenohypophysial tissue in vitro for the detection and estimation of potential corticotrophin releasing factors.", "content": "The cytochemical assay for ACTH has been adapted into a method for the detection and determination of potential corticotropsin releasing factors. Of the many putative transmitter substances tested, only the posterior pituitary polypeptides resembled hypothalamic extracts in causing dose-related increases in both pituitary ACTH content and release. Vasotocin was the most active of the compounds studied and, unlike the vasopressins, its dose-response relationships closely resembled those of hypothalamic extracts. The increase in ACTH release induced by hypothalamic extract of vasopressin was reduced by corticossterone, cortisol or progesterone but not by testosterone or oestradiol, but the increase in pituitary ACTH content was not affected by any of these steroids.", "contents": "The use of corticotrophin production by adenohypophysial tissue in vitro for the detection and estimation of potential corticotrophin releasing factors. The cytochemical assay for ACTH has been adapted into a method for the detection and determination of potential corticotropsin releasing factors. Of the many putative transmitter substances tested, only the posterior pituitary polypeptides resembled hypothalamic extracts in causing dose-related increases in both pituitary ACTH content and release. Vasotocin was the most active of the compounds studied and, unlike the vasopressins, its dose-response relationships closely resembled those of hypothalamic extracts. The increase in ACTH release induced by hypothalamic extract of vasopressin was reduced by corticossterone, cortisol or progesterone but not by testosterone or oestradiol, but the increase in pituitary ACTH content was not affected by any of these steroids."}
{"id": "PMID:191558", "title": "Hypothalamic luteinizing hormone releasing factor and corticotrophin releasing activity in relation to pituitary and plasma hormone levels in male and female rats.", "content": "Hypothalamic corticotrophin releasing (CR) activity and LH-releasing factor (RF) content, and pituitary and plasma LH, FSH and ACTH were measured in adult male and female Wistar rats maintained under 14 h light per day. Hypothalamic LH-RF and pituitary and plasma hormones were estimated by radioimmunoassay while CR-activity was assessed by the amount of ACTH released from hemipituitaries in vitro. Two experiments were carried out on male animals. In the first, some of the animals were kept in a room, distant from the animal house, in which the lighting was reversed with respect to the external environment. In animals exposed to the reversed lighting regime, hypothalamic LH-RF content and pituitary gonadotrophin concentrations were significantly lower than the values in male rats kept in the animal house where they were in close proximity to female rats. In the second experiment, which was carried out on animals which had all been kept in the animal house, there was no significant differences between the LH-RF contents measured at 3-4 h intervals throughout the day. Pituitary LH and FSH contents, but not concentrations, were significantly increased at 12.00 h. There was little differences between the experiments in CR-activity, plasma ACTH concentrations and profiles of pituitary ACTH content and concentration. As expected there was a diurnal rhythm in plasma corticosterone concentrations (determined by competitive protein-binding assay) with the peak occurring between 15.00 and 18.00 h. The profiles of plasma and pituitary ACTH were similar to that of plasma corticosterone. Corticotrophin releasing activity dropped significantly between 12.00 and 16.00 h, but remained steady at the other times. In female rats there were no significant differences between hypothalamic LH-RF content throughout the 4-day cycle. During pro-oestrus the mean LH-RF content rose to teach a high level at 18.00 h at which time plasma LH concentration had risen sharply to a level consistent with the peak of the preovulatory surge. Plasma FSH concentration also rose significantly between 15.00 and 18.00 h of pro-oestrus. At metoestrus and dioestrus, plasma FSH levels were lower in the morning than in the evening. These results suggest that (1) there is no diurnal rhythm in hypothalamic LH-RF, (2) there may be a diurnal rhythm in pituitary gonadotrophin content in the male and in plasma FSH concentration on the days of metoestrus and dioestrus in the female, (3) if a surge of LH-RF does occur on the afternoon of pro-oestrus, the rate of LH-RF synthesis exceeds its release, and (4) the mechanism which regulates gonadotrophin secretion in the male may be affected by factors in the environment other than daylength. The results provide further evidence for the view that the diurnal rhythm of corticosterone secretion is under hypothalamo-hypophysial control.", "contents": "Hypothalamic luteinizing hormone releasing factor and corticotrophin releasing activity in relation to pituitary and plasma hormone levels in male and female rats. Hypothalamic corticotrophin releasing (CR) activity and LH-releasing factor (RF) content, and pituitary and plasma LH, FSH and ACTH were measured in adult male and female Wistar rats maintained under 14 h light per day. Hypothalamic LH-RF and pituitary and plasma hormones were estimated by radioimmunoassay while CR-activity was assessed by the amount of ACTH released from hemipituitaries in vitro. Two experiments were carried out on male animals. In the first, some of the animals were kept in a room, distant from the animal house, in which the lighting was reversed with respect to the external environment. In animals exposed to the reversed lighting regime, hypothalamic LH-RF content and pituitary gonadotrophin concentrations were significantly lower than the values in male rats kept in the animal house where they were in close proximity to female rats. In the second experiment, which was carried out on animals which had all been kept in the animal house, there was no significant differences between the LH-RF contents measured at 3-4 h intervals throughout the day. Pituitary LH and FSH contents, but not concentrations, were significantly increased at 12.00 h. There was little differences between the experiments in CR-activity, plasma ACTH concentrations and profiles of pituitary ACTH content and concentration. As expected there was a diurnal rhythm in plasma corticosterone concentrations (determined by competitive protein-binding assay) with the peak occurring between 15.00 and 18.00 h. The profiles of plasma and pituitary ACTH were similar to that of plasma corticosterone. Corticotrophin releasing activity dropped significantly between 12.00 and 16.00 h, but remained steady at the other times. In female rats there were no significant differences between hypothalamic LH-RF content throughout the 4-day cycle. During pro-oestrus the mean LH-RF content rose to teach a high level at 18.00 h at which time plasma LH concentration had risen sharply to a level consistent with the peak of the preovulatory surge. Plasma FSH concentration also rose significantly between 15.00 and 18.00 h of pro-oestrus. At metoestrus and dioestrus, plasma FSH levels were lower in the morning than in the evening. These results suggest that (1) there is no diurnal rhythm in hypothalamic LH-RF, (2) there may be a diurnal rhythm in pituitary gonadotrophin content in the male and in plasma FSH concentration on the days of metoestrus and dioestrus in the female, (3) if a surge of LH-RF does occur on the afternoon of pro-oestrus, the rate of LH-RF synthesis exceeds its release, and (4) the mechanism which regulates gonadotrophin secretion in the male may be affected by factors in the environment other than daylength. The results provide further evidence for the view that the diurnal rhythm of corticosterone secretion is under hypothalamo-hypophysial control."}
{"id": "PMID:191559", "title": "Releasing factor and hormonal changes in the hypothalamic-pituitary-gonadotrophin and -adrenocorticotrophin systems before and after birth and puberty in male, female and androgenized female rats.", "content": "The hypothalamic content of LH releasing factor (RF), pituitary ACTH and pituitary and plasma LH and FSH were measured by radioimmunoassay from foetal Day 15 to postnatal Day 65. Bioassayable corticotrophin releasing activity was also measured during the postnatal period. Hypothalamic LH-RF was detectable as early as foetal Day 15, increasing gradually until postnatal Day 2 and then steeply between Days 5 and 16. The levels of LH-RF were similar in both male and normal female rats until Day 41, after which the increase which had been occurring from Day 16 continued in the male but not the female. In female rats treated with testosterone propionate neonatally ('androgenized females') the hypothalamic content of LH-RF at Day 9 was significantly less than that in the male or normal female, levels reaching those found in the latter two groups by Days 16-22. The lower level of LH-RF in the androgenized female was associated with pituitary gonadotrophin and plasma FSH levels which were lower than in the normal female until Day 30. In the normal female, vaginal opening was associated with a marked drop in hypothalamic LH-RF content and in pituitary LH and FSH, but in the androgenized female, vaginal opening occurred while hypothalamic LH-RF and pituitary LH levels were still rising. The peaks in pituitary FSH and LH and in plasma LH seen on Days 22, 30 and 41, respectively, in the normal female were each delayed by 8-9 days in the androgenized female. In all three types of animal there was a significant drop in plasma FSH between Days 50 and 65 which was associated with a significant increase in pituitary FSH in the male and a significant decrease in pituitary FSH in the androgenized female rats. The day 17 foetal pituitary gland also contained ACTH, and again levels of this hormone rose steeply between Days 5 and 9. In contrast to the gonadotrophins, there was a marked divergence between the pituitary content and concentration of ACTH: content rose while concentration remained relatively steady after Day 9. There was no major difference in pituitary ACTH levels between the three types of animal throughout the study; however, around Days 16 and 50, corticotrophin releasing activity was higher in males and androgenized females compared with that in normal females.", "contents": "Releasing factor and hormonal changes in the hypothalamic-pituitary-gonadotrophin and -adrenocorticotrophin systems before and after birth and puberty in male, female and androgenized female rats. The hypothalamic content of LH releasing factor (RF), pituitary ACTH and pituitary and plasma LH and FSH were measured by radioimmunoassay from foetal Day 15 to postnatal Day 65. Bioassayable corticotrophin releasing activity was also measured during the postnatal period. Hypothalamic LH-RF was detectable as early as foetal Day 15, increasing gradually until postnatal Day 2 and then steeply between Days 5 and 16. The levels of LH-RF were similar in both male and normal female rats until Day 41, after which the increase which had been occurring from Day 16 continued in the male but not the female. In female rats treated with testosterone propionate neonatally ('androgenized females') the hypothalamic content of LH-RF at Day 9 was significantly less than that in the male or normal female, levels reaching those found in the latter two groups by Days 16-22. The lower level of LH-RF in the androgenized female was associated with pituitary gonadotrophin and plasma FSH levels which were lower than in the normal female until Day 30. In the normal female, vaginal opening was associated with a marked drop in hypothalamic LH-RF content and in pituitary LH and FSH, but in the androgenized female, vaginal opening occurred while hypothalamic LH-RF and pituitary LH levels were still rising. The peaks in pituitary FSH and LH and in plasma LH seen on Days 22, 30 and 41, respectively, in the normal female were each delayed by 8-9 days in the androgenized female. In all three types of animal there was a significant drop in plasma FSH between Days 50 and 65 which was associated with a significant increase in pituitary FSH in the male and a significant decrease in pituitary FSH in the androgenized female rats. The day 17 foetal pituitary gland also contained ACTH, and again levels of this hormone rose steeply between Days 5 and 9. In contrast to the gonadotrophins, there was a marked divergence between the pituitary content and concentration of ACTH: content rose while concentration remained relatively steady after Day 9. There was no major difference in pituitary ACTH levels between the three types of animal throughout the study; however, around Days 16 and 50, corticotrophin releasing activity was higher in males and androgenized females compared with that in normal females."}
{"id": "PMID:191562", "title": "Simultaneous radioimmunoassay for corticosterone and deoxycortisol in human serum: sex differences in the mean serum concentrations.", "content": "A specific radioimmunoassay is described which allows the simultaneous determination of serum corticosterone and deoxycortisol. The method involves extraction with dichloromethane, purification by paper chromatography in a modified Bush-system and quantitation by radioimmunoassay. The normal serum concentration of both steroids were found to be dependent on sex and menstrual cycle. Mean concentrations (+/- S.D.) in males, females (follicular phase) and females (luteal phase) were 4210 +/- 2170 ng/1,2410 + 1480 ng/1 and 4390 +/- 2320 ng/1 for corticosterone and 499 +/- 273 ng/1, 207 +/- 152 ng/1 and 335 +/- 182 ng/1 for deoxycortisol. After adrenal stimulation by corticotropin itself or by insulin induced hypoglycemia, the serum concentrations of corticosterone became significantly higher than those of deoxycortisol. After oral administration of dexamethasone serum concentrations of both steroids were suppressed to levels below the limit of the normal range. One hour after oral metyrapone administration at midnight, serum corticosterone decreased, while serum deoxycortisol increased by a factor of about five. After eight hours serum concentrations of both steroids were increased considerably. Corticosterone attained levels slightly higher than the normal range and deoxycortisol rose to levels which were higher than the normal mean concentrations by a factor of about 500.", "contents": "Simultaneous radioimmunoassay for corticosterone and deoxycortisol in human serum: sex differences in the mean serum concentrations. A specific radioimmunoassay is described which allows the simultaneous determination of serum corticosterone and deoxycortisol. The method involves extraction with dichloromethane, purification by paper chromatography in a modified Bush-system and quantitation by radioimmunoassay. The normal serum concentration of both steroids were found to be dependent on sex and menstrual cycle. Mean concentrations (+/- S.D.) in males, females (follicular phase) and females (luteal phase) were 4210 +/- 2170 ng/1,2410 + 1480 ng/1 and 4390 +/- 2320 ng/1 for corticosterone and 499 +/- 273 ng/1, 207 +/- 152 ng/1 and 335 +/- 182 ng/1 for deoxycortisol. After adrenal stimulation by corticotropin itself or by insulin induced hypoglycemia, the serum concentrations of corticosterone became significantly higher than those of deoxycortisol. After oral administration of dexamethasone serum concentrations of both steroids were suppressed to levels below the limit of the normal range. One hour after oral metyrapone administration at midnight, serum corticosterone decreased, while serum deoxycortisol increased by a factor of about five. After eight hours serum concentrations of both steroids were increased considerably. Corticosterone attained levels slightly higher than the normal range and deoxycortisol rose to levels which were higher than the normal mean concentrations by a factor of about 500."}
{"id": "PMID:191563", "title": "Turnover of cytochrome C in skeletal muscle of green sunfish (Lepomis cyanellus, R.) during thermal acclimation.", "content": "The concentration of cytochrome c in the skeletal muscle of the green sunfish (Lepomis cyanellus) increases with decreasing temperature of acclimation: 1.51 +/- 0.09, 1.17 +/- 0.03, and 0.98 +/- 0.07 nanomoles per gram wet weight from muscle of animals acclimated to 5 degrees, 15 degrees, and 25 degrees C, respectively. The roles of synthesis and degradation of cytochrome c during thermal acclimation were investigated by measurement of loss of specific radioactivity from cytochrome c and from total mitochondrial heme protein, and by analysis of the rate of change in concentration of cytochrome c. The radioisotope used was 14C-delta-aminolevulinic acid, a non-reutilizable heme precursor. At 25 degrees C, the half-life of cytochrome c was 7.1 days based on radioactivity measurements and 5.6 days based on change in concentration. Statistical analysis showed no significant difference in half-lives obtained by the two methods. The half-life of total mitochondrial heme protein was determined to be 5.7 days on the basis of radioactivity data, under the same conditions. No significant difference was found between the rate of turnover of the heme protein pool from mitochondria and either measurement for cytochrome c at 25 degrees C. At an acclimation temperature of 5 degrees C, the half-life of cytochrome c from skeletal muscle was 13.7 days based upon changes in concentration. At low acclimation temperature, radioactive label was retained in acid-soluble form by fish for many days, precluding measurement of half-life by this technique. Transfer of fish from 25 degrees to 5 degrees C resulted in a rapid decrease of approximately 40% in rates in synthesis of skeletal muscle cytochrome c, and a concomitant decrease in the degradation rate constant for this molecule of approximately 60%. The disproportionality in temperature-sensitivities of these two processes leads to an approximately 50% net increase in the concentration of cytochrome c during acclimation. In transfer from 5 degrees to 25 degrees C, the converse, rapid readjustments in synthetic and degradative parameters occur, resulting in the observed decrease in cytochrome c content.", "contents": "Turnover of cytochrome C in skeletal muscle of green sunfish (Lepomis cyanellus, R.) during thermal acclimation. The concentration of cytochrome c in the skeletal muscle of the green sunfish (Lepomis cyanellus) increases with decreasing temperature of acclimation: 1.51 +/- 0.09, 1.17 +/- 0.03, and 0.98 +/- 0.07 nanomoles per gram wet weight from muscle of animals acclimated to 5 degrees, 15 degrees, and 25 degrees C, respectively. The roles of synthesis and degradation of cytochrome c during thermal acclimation were investigated by measurement of loss of specific radioactivity from cytochrome c and from total mitochondrial heme protein, and by analysis of the rate of change in concentration of cytochrome c. The radioisotope used was 14C-delta-aminolevulinic acid, a non-reutilizable heme precursor. At 25 degrees C, the half-life of cytochrome c was 7.1 days based on radioactivity measurements and 5.6 days based on change in concentration. Statistical analysis showed no significant difference in half-lives obtained by the two methods. The half-life of total mitochondrial heme protein was determined to be 5.7 days on the basis of radioactivity data, under the same conditions. No significant difference was found between the rate of turnover of the heme protein pool from mitochondria and either measurement for cytochrome c at 25 degrees C. At an acclimation temperature of 5 degrees C, the half-life of cytochrome c from skeletal muscle was 13.7 days based upon changes in concentration. At low acclimation temperature, radioactive label was retained in acid-soluble form by fish for many days, precluding measurement of half-life by this technique. Transfer of fish from 25 degrees to 5 degrees C resulted in a rapid decrease of approximately 40% in rates in synthesis of skeletal muscle cytochrome c, and a concomitant decrease in the degradation rate constant for this molecule of approximately 60%. The disproportionality in temperature-sensitivities of these two processes leads to an approximately 50% net increase in the concentration of cytochrome c during acclimation. In transfer from 5 degrees to 25 degrees C, the converse, rapid readjustments in synthetic and degradative parameters occur, resulting in the observed decrease in cytochrome c content."}
{"id": "PMID:191564", "title": "Cyclic AMP regulation of active chloride transport in the rectal gland of marine elasmobranchs.", "content": "Active transport of chloride in the salt secreting rectal gland of the dogfish Squalus acanthias is markedly stimulated by the addition of theophylline (0.01 to 5 mM) or dibutyryl cyclic AMP (0.05 mM) during in vitro perfusion. The effect occurs promptly and may persist for two hours. Specific hormonal effectors have not yet been identified. The isolated perfused rectal gland thus offers a unique opportunity to examine the cellular mechanisms of active chloride secretion.", "contents": "Cyclic AMP regulation of active chloride transport in the rectal gland of marine elasmobranchs. Active transport of chloride in the salt secreting rectal gland of the dogfish Squalus acanthias is markedly stimulated by the addition of theophylline (0.01 to 5 mM) or dibutyryl cyclic AMP (0.05 mM) during in vitro perfusion. The effect occurs promptly and may persist for two hours. Specific hormonal effectors have not yet been identified. The isolated perfused rectal gland thus offers a unique opportunity to examine the cellular mechanisms of active chloride secretion."}
{"id": "PMID:191566", "title": "Idiopathic orthostatic hypotension from failure of noradrenaline release in a patient with vasomotor innervation.", "content": "A 26 year old man is described with life-long orthostatic hypotension unrelated to autonomic nerve degeneration and apparently due to failure of peripheral noradrenaline realese. Tests of parasympathetic and sympathetic cholinergic nerve function were normal, but sympathetic adrenergic activity was defective. Thus blood pressure regulation was abnoraml. There was no pressor response to tyramine, an indirect sympathomimetic drug, but a marked pressor response to the directly acting sympathomimetic drugs phenylephrine and noradrenaline. On standing there was a progressive fall rather than a rise in circulating noradrenaline concentrations, although adrenaline levels rose normally. The pupils showed diminished responses to ephedrine and cocaine, and a normal response to phenylephrine. Fluorescence microscopy of blood bessels showed that they were innervated with adrenergic nerves. His orthostatic hypotenstion responded well to oral phenylephrine (50 mg five times daily) but not to other forms of therapy. It is suggested that this patient's symptoms were due to failure of noradrenaline release even though sympathetic adrenergic nerves were present. We therfore wish to draw attention to a further cause of orthostatic hypotension, failure of peripheral noradrenaline release without autonomic neuropathy.", "contents": "Idiopathic orthostatic hypotension from failure of noradrenaline release in a patient with vasomotor innervation. A 26 year old man is described with life-long orthostatic hypotension unrelated to autonomic nerve degeneration and apparently due to failure of peripheral noradrenaline realese. Tests of parasympathetic and sympathetic cholinergic nerve function were normal, but sympathetic adrenergic activity was defective. Thus blood pressure regulation was abnoraml. There was no pressor response to tyramine, an indirect sympathomimetic drug, but a marked pressor response to the directly acting sympathomimetic drugs phenylephrine and noradrenaline. On standing there was a progressive fall rather than a rise in circulating noradrenaline concentrations, although adrenaline levels rose normally. The pupils showed diminished responses to ephedrine and cocaine, and a normal response to phenylephrine. Fluorescence microscopy of blood bessels showed that they were innervated with adrenergic nerves. His orthostatic hypotenstion responded well to oral phenylephrine (50 mg five times daily) but not to other forms of therapy. It is suggested that this patient's symptoms were due to failure of noradrenaline release even though sympathetic adrenergic nerves were present. We therfore wish to draw attention to a further cause of orthostatic hypotension, failure of peripheral noradrenaline release without autonomic neuropathy."}
{"id": "PMID:191567", "title": "Prolonged conduction block with axonal degeneration. An electrophysiological study.", "content": "Serial electrophysiological studies were performed in a case of 'tourniquet paralysis' of the upper limb after the application of an Esmarch bandage above the elbow. Three months after onset of paralysis, nerve conduction was reduced to a quarter of normal between elbow and and axilla along the few fibres still conducting through the lesion, but was normal distal to the block. Seven months after nerve damage, EMG showed evidence of reinnervation after Wallerian degeneration, and half the nerve fibres had recovered from the conduction block. Thirteen months after nerve injury clinical examination and nerve conduction were normal, but EMG still showed evidence of partial denervation.", "contents": "Prolonged conduction block with axonal degeneration. An electrophysiological study. Serial electrophysiological studies were performed in a case of 'tourniquet paralysis' of the upper limb after the application of an Esmarch bandage above the elbow. Three months after onset of paralysis, nerve conduction was reduced to a quarter of normal between elbow and and axilla along the few fibres still conducting through the lesion, but was normal distal to the block. Seven months after nerve damage, EMG showed evidence of reinnervation after Wallerian degeneration, and half the nerve fibres had recovered from the conduction block. Thirteen months after nerve injury clinical examination and nerve conduction were normal, but EMG still showed evidence of partial denervation."}
{"id": "PMID:191568", "title": "Nerve, muscle, and serotonin.", "content": "Effects of serotonin one neuromuscular transmission and muscle contraction were studied in the tibialis anterior of rabbits. Serotonin antagonised the Mg++-induced block of transmission, and also provided dual effects on the curare-induced block, anti-curare phase followed by curare-potentiating phase. Independent of transmission processes, serotonin caused a reduction in twitch tension, mainly associated with decreased acceleration of twitch development. These serotonin actions were independent of vascular changes; pharmacological mechanisms are discussed in comparison with those of adrenaline and isoprenaline. A possible role of serotonin in causing a myopathy is proposed.", "contents": "Nerve, muscle, and serotonin. Effects of serotonin one neuromuscular transmission and muscle contraction were studied in the tibialis anterior of rabbits. Serotonin antagonised the Mg++-induced block of transmission, and also provided dual effects on the curare-induced block, anti-curare phase followed by curare-potentiating phase. Independent of transmission processes, serotonin caused a reduction in twitch tension, mainly associated with decreased acceleration of twitch development. These serotonin actions were independent of vascular changes; pharmacological mechanisms are discussed in comparison with those of adrenaline and isoprenaline. A possible role of serotonin in causing a myopathy is proposed."}
{"id": "PMID:191569", "title": "Toxic polyneuropathies in Italy due to leather cement poisoning in shoe industries. A light- and electron-microscopic study.", "content": "The peripheral nerve biopsy specimens of 4 cases of toxic polyneruopathies induced by exposure to leather cement in shoe industries were studied. Analysis of the cements used in the manufacturing process proved them to contain n-hexane as a volatile substance. Light- and electron-microscopic examination of nerve biopsies showed segmental swelling of axons due to the accumulation of packed filaments and thinning of the overlying myelin sheath. Neither active nerve fibre degeneration nor regeneration were frequently seen. It has been suggested that features of so-called giant axonal neuropathy are the most common pattern of peripheral nerve degeneration in chronic n-hexane intoxication.", "contents": "Toxic polyneuropathies in Italy due to leather cement poisoning in shoe industries. A light- and electron-microscopic study. The peripheral nerve biopsy specimens of 4 cases of toxic polyneruopathies induced by exposure to leather cement in shoe industries were studied. Analysis of the cements used in the manufacturing process proved them to contain n-hexane as a volatile substance. Light- and electron-microscopic examination of nerve biopsies showed segmental swelling of axons due to the accumulation of packed filaments and thinning of the overlying myelin sheath. Neither active nerve fibre degeneration nor regeneration were frequently seen. It has been suggested that features of so-called giant axonal neuropathy are the most common pattern of peripheral nerve degeneration in chronic n-hexane intoxication."}
{"id": "PMID:191570", "title": "Fingerprint inclusions. Ultrastructural demonstration of muscle fiber type specificity.", "content": "Fingerprint inclusions were identified in the skeletal muscle of a child with severe hypotonia. The mean Z-line and M-line widths from each of 19 muscle fibers containing the fingerprint inclusions were calculated. The mean Z-line widths were 85-99 nm, and the mean M-line widths were 75-101 nm. According to out present system of fiber typing, all of these fibers would be classified as Type I. The possible pathogenesis and fiber type specificity of the fingerprint inclusion is discussed.", "contents": "Fingerprint inclusions. Ultrastructural demonstration of muscle fiber type specificity. Fingerprint inclusions were identified in the skeletal muscle of a child with severe hypotonia. The mean Z-line and M-line widths from each of 19 muscle fibers containing the fingerprint inclusions were calculated. The mean Z-line widths were 85-99 nm, and the mean M-line widths were 75-101 nm. According to out present system of fiber typing, all of these fibers would be classified as Type I. The possible pathogenesis and fiber type specificity of the fingerprint inclusion is discussed."}
{"id": "PMID:191571", "title": "Hypobetalipoproteinemia with abnormal prebetalipoprotein.", "content": "A 47-year-old man who had cerebellar ataxia and low plasma lipid and lipoprotein levels is reported. His tendon reflexes were hyperactive and the plantar responses were extensor. There was no acanthocytosis. Total lipids (380 mg/dl), total cholesterol (106 mg/dl), esterified cholesterol (74 mg/dl), triglyceride (58 mg/dl), phospholipids (124 mg/dl) and free fatty acids (303 muequiv./l) were generally decreased. A disturbance of lipid absorption due to a defect of chylomicron formation and hepatic steatosis were also disclosed. On lipoprotein electrophoresis, prebetalipoprotein was very faint and migrated more slowly than normal. Betalipoprotein and alphalipoprotein were moderately reduced in concentration but migrated normally. The concentration of isolated VLDL was only one-tenth of that in normal subjects and it migrated as slow prebetalipoprotein. Although the lipid composition of VLDL was similar to that of normal VLDL, the lack of minor components was disclosed by SDS-PAG electrophoresis. Incorporation of [1-14C]acetate into VLDL lipids was significantly reduced to a greater extent than that of LDL and HDL. From these findings, we discuss the possibility that hypobetalipoproteinemia results from impaired VLDL synthesis.", "contents": "Hypobetalipoproteinemia with abnormal prebetalipoprotein. A 47-year-old man who had cerebellar ataxia and low plasma lipid and lipoprotein levels is reported. His tendon reflexes were hyperactive and the plantar responses were extensor. There was no acanthocytosis. Total lipids (380 mg/dl), total cholesterol (106 mg/dl), esterified cholesterol (74 mg/dl), triglyceride (58 mg/dl), phospholipids (124 mg/dl) and free fatty acids (303 muequiv./l) were generally decreased. A disturbance of lipid absorption due to a defect of chylomicron formation and hepatic steatosis were also disclosed. On lipoprotein electrophoresis, prebetalipoprotein was very faint and migrated more slowly than normal. Betalipoprotein and alphalipoprotein were moderately reduced in concentration but migrated normally. The concentration of isolated VLDL was only one-tenth of that in normal subjects and it migrated as slow prebetalipoprotein. Although the lipid composition of VLDL was similar to that of normal VLDL, the lack of minor components was disclosed by SDS-PAG electrophoresis. Incorporation of [1-14C]acetate into VLDL lipids was significantly reduced to a greater extent than that of LDL and HDL. From these findings, we discuss the possibility that hypobetalipoproteinemia results from impaired VLDL synthesis."}
{"id": "PMID:191572", "title": "Functional organization of vestibular and visual inputs to neck and forelimb motoneurons in the frog.", "content": "1. Intracellular responses in neck and forelimb motoneurons to electrical stimulation of the vestibular nerve, the optic tectum, and the optic nerve were studied in frog. 2. Stimulation of the anterior branch of the vestibular nerve typically produced EPSPs, bilaterally, in neck, shoulder (DOR), and forelimb extensor (TRI, RAD) motoneurons, and bilateral IPSPs in forelimb adductor (PED) and flexor (ULN, COR) motoneurons. 3. Latencies of PSPs recorded in neck, shoulder, and proximal extensor motoneurons (TRI) were mostly in the disynaptic range, whereas many of those recorded in distal extensor (RAD) and in adductor and flexor motoneurons involved three synapses. 4. Lesion of the vestibulospinal fibers greatly reduced the vestibular nerve-evoked field potentials in the spinal cord and the occurrence of PSPs in forelimb motoneurons. These results as well as the latency measurements suggest that the pathway linking vestibular nerve and forelimb motoneurons mainly consists of vestibulospinal fibers, though involvement of other structures for production of later PSPs could not be completely ruled out. Hemisection of the brain stem at its most caudal level showed that the pathway to the contralateral motoneurons crosses at the level of brain stem as well as in the spinal cord. 5. Stimulation of the optic tectum produced EPSPs, IPSPs, and a mixture of EPSPs and IPSPs in neck, shoulder, and forelimb motoneurons, bilaterally. Most frequently, a combination of an excitation and inhibition was observed. The pathway from the optic tectum to neck and limb motoneurons is at least dysnaptic in nature. 6. Stimulation of the optic nerve produced IPSPs and a mixture of EPSPs and IPSPs in neck and forelimb motoneurons. Impulses originating from the optic nerve descend as far as to lumbar motoneurons producing EPSP-IPSP sequences bilaterally. 7. Interaction studies suggested that the vestibular and optic pathways to neck and forelimb motoneurons are separate from each other so that the site of integration of vestibular and visual input occurs at the level of motoneurons. 8. Evidence for electronic coupling among forelimb motoneurons and electrical synaptic transmission in th pathway linking vestibular nerve and forelimb motoneurons is presented.", "contents": "Functional organization of vestibular and visual inputs to neck and forelimb motoneurons in the frog. 1. Intracellular responses in neck and forelimb motoneurons to electrical stimulation of the vestibular nerve, the optic tectum, and the optic nerve were studied in frog. 2. Stimulation of the anterior branch of the vestibular nerve typically produced EPSPs, bilaterally, in neck, shoulder (DOR), and forelimb extensor (TRI, RAD) motoneurons, and bilateral IPSPs in forelimb adductor (PED) and flexor (ULN, COR) motoneurons. 3. Latencies of PSPs recorded in neck, shoulder, and proximal extensor motoneurons (TRI) were mostly in the disynaptic range, whereas many of those recorded in distal extensor (RAD) and in adductor and flexor motoneurons involved three synapses. 4. Lesion of the vestibulospinal fibers greatly reduced the vestibular nerve-evoked field potentials in the spinal cord and the occurrence of PSPs in forelimb motoneurons. These results as well as the latency measurements suggest that the pathway linking vestibular nerve and forelimb motoneurons mainly consists of vestibulospinal fibers, though involvement of other structures for production of later PSPs could not be completely ruled out. Hemisection of the brain stem at its most caudal level showed that the pathway to the contralateral motoneurons crosses at the level of brain stem as well as in the spinal cord. 5. Stimulation of the optic tectum produced EPSPs, IPSPs, and a mixture of EPSPs and IPSPs in neck, shoulder, and forelimb motoneurons, bilaterally. Most frequently, a combination of an excitation and inhibition was observed. The pathway from the optic tectum to neck and limb motoneurons is at least dysnaptic in nature. 6. Stimulation of the optic nerve produced IPSPs and a mixture of EPSPs and IPSPs in neck and forelimb motoneurons. Impulses originating from the optic nerve descend as far as to lumbar motoneurons producing EPSP-IPSP sequences bilaterally. 7. Interaction studies suggested that the vestibular and optic pathways to neck and forelimb motoneurons are separate from each other so that the site of integration of vestibular and visual input occurs at the level of motoneurons. 8. Evidence for electronic coupling among forelimb motoneurons and electrical synaptic transmission in th pathway linking vestibular nerve and forelimb motoneurons is presented."}
{"id": "PMID:191573", "title": "Physiological and kinetic properties of cholinergic receptors activated by multiaction interneurons in buccal ganglia of Aplysia.", "content": "1. Neurons of Aplysia buccal ganglia contain three types of acetylcholine (ACh) receptors, each of which has been characterized by its sensitivity to inhibitors and kinetics of desensitization and by the properties of the conductance change it controls, including reversal potential, major ion, and functional consequence. The receptors are classified as depolarizing, slowly decrementing hyperpolarizing, and rapidly decrementing hyperpolarizing. Identified neurons are innervated by identified cholinergic multiaction interneurons; the form of the postsynaptic potential produced depends on the number and class of receptor found on each cell. 2. Interneuronal action potentials produce monosynaptic IPSPs by activating slowly decrementing hyperpolarizing receptors on seven cells in each ganglion. The IPSP reversal potential of 75 mV is shifted 42 mV in a depolarizing direction in Cl = free seawater. The ACh response has a reversal potential identical to that of the PSP; the PSP is blocked by 10(-4) g/ml curare but unaffected by hexamethonium. Interneuronal action potentials also produce monosynaptic EPSPs with a -14 mV extrapolated reversal potential by activating depolarizing receptors on one cell in each ganglion. This PSP is blocked by 10(-4) g/ml hexamethonium and mimicked by a Na-dependent ACh response. 3. Each interneuronal action potential also produces a diphasic depolarizing-hyperpolarizing synaptic potential in one cell in each ganglion as a result of released ACh acting on two classes of postsynaptic receptor on the same cell. One of these receptors is depolarizing; the other is a rapidly decrementing hyperpolarizing receptor. The two differ in their sensitivity to inhibitors, and the conductance changes they produce differ in their reversal potential, duration, and functional consequences. Both components can be mimicked by iontophoretic application of ACh. 4. Although the hyperpolarizing receptors on the inhibitory and diphasic follower cells have similar sensitivity to inhibitors and control similar conductance changes, they differ in their kinetics of desensitization. The hyperpolarizing receptor on the diphasic cell shows marked decrement to repeated presynaptic action potentials and to repeated iontophoretic application of ACh. This decrement is greater than that seen in either the hyperpolarizing receptor on the inhibitory follower cell or the depolarizing receptor on the dual follower cell. The shape of the PSP in the diphasic follower and its effect on firing of the cell are thus functions of both membrane potential and the degree of desensitization of the receptor. 5. Rate of desensitization is, therefore, an additional criterion for characterizing otherwise similar receptors for neurotransmitters.", "contents": "Physiological and kinetic properties of cholinergic receptors activated by multiaction interneurons in buccal ganglia of Aplysia. 1. Neurons of Aplysia buccal ganglia contain three types of acetylcholine (ACh) receptors, each of which has been characterized by its sensitivity to inhibitors and kinetics of desensitization and by the properties of the conductance change it controls, including reversal potential, major ion, and functional consequence. The receptors are classified as depolarizing, slowly decrementing hyperpolarizing, and rapidly decrementing hyperpolarizing. Identified neurons are innervated by identified cholinergic multiaction interneurons; the form of the postsynaptic potential produced depends on the number and class of receptor found on each cell. 2. Interneuronal action potentials produce monosynaptic IPSPs by activating slowly decrementing hyperpolarizing receptors on seven cells in each ganglion. The IPSP reversal potential of 75 mV is shifted 42 mV in a depolarizing direction in Cl = free seawater. The ACh response has a reversal potential identical to that of the PSP; the PSP is blocked by 10(-4) g/ml curare but unaffected by hexamethonium. Interneuronal action potentials also produce monosynaptic EPSPs with a -14 mV extrapolated reversal potential by activating depolarizing receptors on one cell in each ganglion. This PSP is blocked by 10(-4) g/ml hexamethonium and mimicked by a Na-dependent ACh response. 3. Each interneuronal action potential also produces a diphasic depolarizing-hyperpolarizing synaptic potential in one cell in each ganglion as a result of released ACh acting on two classes of postsynaptic receptor on the same cell. One of these receptors is depolarizing; the other is a rapidly decrementing hyperpolarizing receptor. The two differ in their sensitivity to inhibitors, and the conductance changes they produce differ in their reversal potential, duration, and functional consequences. Both components can be mimicked by iontophoretic application of ACh. 4. Although the hyperpolarizing receptors on the inhibitory and diphasic follower cells have similar sensitivity to inhibitors and control similar conductance changes, they differ in their kinetics of desensitization. The hyperpolarizing receptor on the diphasic cell shows marked decrement to repeated presynaptic action potentials and to repeated iontophoretic application of ACh. This decrement is greater than that seen in either the hyperpolarizing receptor on the inhibitory follower cell or the depolarizing receptor on the dual follower cell. The shape of the PSP in the diphasic follower and its effect on firing of the cell are thus functions of both membrane potential and the degree of desensitization of the receptor. 5. Rate of desensitization is, therefore, an additional criterion for characterizing otherwise similar receptors for neurotransmitters."}
{"id": "PMID:191574", "title": "Organization of visual inputs to interneurons of lateral geniculate nucleus of the cat.", "content": "1. Two groups of interneurons that are involved in the organization of the lateral geniculate nucleus (LGN) are described. The cell bodies of one group lie within the LGN; these units are referred to as intrageniculate. The cell bodies of the other group are found immediately above the LGN at its border with the perigeniculate nucleus; these units are referred to as perigeniculate. 2. Intrageniculate interneurons have center-surround receptive fields that resemble those of relay (principal) cells. They can be subdivided into brisk or sluggish and sustained or transient categories. They are stimulated transsynaptically from the visual cortex and have a characteristic variation in the latency of their spike response to such stimulation both at threshold and for suprathreshold stimuli. The pathway for this stimulation appears to be via cortical efferents to the LGN. Intrageniculate interneurons receive direct, monosynaptic retinal inputs, as determined by recording simultaneously from such interneurons and from the ganglion cells which provide excitatory input to them. Similar to relay cells, they are shown to have one or two major ganglion cell inputs. 3. Perigeniculate interneurons are generally binocularly innervated and give on-off responses to small spot stimuli throughout their receptive field. They respond well to rapid movement of large targets. They respond to electrical stimulation of the retina with a spike latency that falls between that of brisk transient and brisk sustained relay cells. This latency is one synaptic delay longer than that of brisk transient relay cell activation and suggests that they are excited by axon collaterals of these relay cells. Electrical stimulation of the visual cortex is also consistent with this model; the latency of the response of perigeniculate interneurons is approximately one synaptic delay longer than the latency of the response of brisk transient relay cells. 4. The interneuronal pathways described are consistent with proposed circuits that subserve the generation of IPSPs that arise in response to optic nerve and visual cortical stimulation. We now show that such inhibition has feed-forward (intrageniculate) and feed-back (perigeniculate) components that are mediated by two different classes of geniculate interneurons. It is suggested that the intrageniculate interneurons are involved in precise, spatially organized inhibition and that the perigeniculate interneurons are part of a more general, diffuse inhibitory system that modulates LGN excitability.", "contents": "Organization of visual inputs to interneurons of lateral geniculate nucleus of the cat. 1. Two groups of interneurons that are involved in the organization of the lateral geniculate nucleus (LGN) are described. The cell bodies of one group lie within the LGN; these units are referred to as intrageniculate. The cell bodies of the other group are found immediately above the LGN at its border with the perigeniculate nucleus; these units are referred to as perigeniculate. 2. Intrageniculate interneurons have center-surround receptive fields that resemble those of relay (principal) cells. They can be subdivided into brisk or sluggish and sustained or transient categories. They are stimulated transsynaptically from the visual cortex and have a characteristic variation in the latency of their spike response to such stimulation both at threshold and for suprathreshold stimuli. The pathway for this stimulation appears to be via cortical efferents to the LGN. Intrageniculate interneurons receive direct, monosynaptic retinal inputs, as determined by recording simultaneously from such interneurons and from the ganglion cells which provide excitatory input to them. Similar to relay cells, they are shown to have one or two major ganglion cell inputs. 3. Perigeniculate interneurons are generally binocularly innervated and give on-off responses to small spot stimuli throughout their receptive field. They respond well to rapid movement of large targets. They respond to electrical stimulation of the retina with a spike latency that falls between that of brisk transient and brisk sustained relay cells. This latency is one synaptic delay longer than that of brisk transient relay cell activation and suggests that they are excited by axon collaterals of these relay cells. Electrical stimulation of the visual cortex is also consistent with this model; the latency of the response of perigeniculate interneurons is approximately one synaptic delay longer than the latency of the response of brisk transient relay cells. 4. The interneuronal pathways described are consistent with proposed circuits that subserve the generation of IPSPs that arise in response to optic nerve and visual cortical stimulation. We now show that such inhibition has feed-forward (intrageniculate) and feed-back (perigeniculate) components that are mediated by two different classes of geniculate interneurons. It is suggested that the intrageniculate interneurons are involved in precise, spatially organized inhibition and that the perigeniculate interneurons are part of a more general, diffuse inhibitory system that modulates LGN excitability."}
{"id": "PMID:191575", "title": "Immunobiology of primary intracranial tumors. Part 1: studies of the cellular and humoral general immune competence of brain-tumor patients.", "content": "Cellular and humoral immune parameters were evaluated in a series of brain-tumor patients, 42 with glioblastoma multiforme, 17 with other anaplastic gliomas, and 17 with meningiomas. A degree of anergy was found, which seems in the group as a whole to be proportional to the degree of anaplasia. In addition, serial bimonthyl testing in individual cases revealed further reduction in certain immune responses coincident with clinical decline.", "contents": "Immunobiology of primary intracranial tumors. Part 1: studies of the cellular and humoral general immune competence of brain-tumor patients. Cellular and humoral immune parameters were evaluated in a series of brain-tumor patients, 42 with glioblastoma multiforme, 17 with other anaplastic gliomas, and 17 with meningiomas. A degree of anergy was found, which seems in the group as a whole to be proportional to the degree of anaplasia. In addition, serial bimonthyl testing in individual cases revealed further reduction in certain immune responses coincident with clinical decline."}
{"id": "PMID:191576", "title": "Cyclic AMP and adenyl cyclase in brain tumors.", "content": "Some of the regulatory mechanisms of cyclic adenosine monophosphate (AMP) production in human brain tumors were investigated by assessing both cyclic AMP levels and adenyl cyclase activity. A large disparity was found between the levels of cyclic AMP of normal brain and brain-tumor tissue. Cyclic AMP levels were much lower in brain tumors (25.8 pmoles (picomoles)/mg protein) than in normal brain (98.8 pmoles/mg protein). These studies also show that the abnormally low levels of cyclic AMP in tumors parallel those of adenyl cyclase. The mean adenyl cyclase activity of brain tissue was found to be 111.0 pmoles of cyclic AMP/min/mg protein, while that of the tumor was only 23.0 pmoles/min/mg protein. Levels of cyclic AMP and adenyl cyclase activity were inversely related to the degree of malignancy. Attempts to stimulate adenyl cyclase in homogenates of human brain and brain tumors resulted in a similar response in both tissues. Norepinephrone was the most effective stimulant and produced a two- to threefold increase in cyclic AMP production, while histamine had no effect. It is concluded that one of the factors governing tumor growth may be a defect in the adenyl cyclase system.", "contents": "Cyclic AMP and adenyl cyclase in brain tumors. Some of the regulatory mechanisms of cyclic adenosine monophosphate (AMP) production in human brain tumors were investigated by assessing both cyclic AMP levels and adenyl cyclase activity. A large disparity was found between the levels of cyclic AMP of normal brain and brain-tumor tissue. Cyclic AMP levels were much lower in brain tumors (25.8 pmoles (picomoles)/mg protein) than in normal brain (98.8 pmoles/mg protein). These studies also show that the abnormally low levels of cyclic AMP in tumors parallel those of adenyl cyclase. The mean adenyl cyclase activity of brain tissue was found to be 111.0 pmoles of cyclic AMP/min/mg protein, while that of the tumor was only 23.0 pmoles/min/mg protein. Levels of cyclic AMP and adenyl cyclase activity were inversely related to the degree of malignancy. Attempts to stimulate adenyl cyclase in homogenates of human brain and brain tumors resulted in a similar response in both tissues. Norepinephrone was the most effective stimulant and produced a two- to threefold increase in cyclic AMP production, while histamine had no effect. It is concluded that one of the factors governing tumor growth may be a defect in the adenyl cyclase system."}
{"id": "PMID:191577", "title": "Effects of cyclic AMP and dibutyryl cyclic AMP on cerebral hemodynamics and metabolism in the baboon.", "content": "Adenosine 3',5'-cycle monophosphate (cyclic AMP) (0.5 mg/kg) was infused into the carotid artery of baboons anesthesized with sodium pentobarbital, causing a biphasic increase in cerebral blood flow (CBF) and reduction in cerebrovascular resistance (CVR) associated in each phase with stimulation of cerebral metabolism evidenced by increased cerebral oxygen consumption (COMRO2) and cerebral glucose consumption (CMRG1). Intracarotid dibutyryl cyclic AMP (0.5 mg/kg) caused a monophasic increase in CBF and reduction of CVR but failed to alter cerebral metabolism. This may be due to its rapid removal from the circulation with ineffective passage across the blood-brain barrier since intracisternal infusion of dibutyryl cyclic AMP caused sustained increase in CBF, CMRO2 and CMRG1 and reduction in CVR. Intracarotid AMP (0.4 mg/kg) and adenosine (0.3 mg/kg) caused an immediate and more marked increase in CBF and decrease in CVR unassociated with cerebral metabolic change making it unlikely that the observed effects of cyclic AMP can be attributed to its breakdown products. Cyclic AMP or its dibutyryl derivative may alter cerebral metabolism secondary to neuronal activation but increase in glucose/oxygen utilization ratio after intracarotid cyclic AMP and intracisternal dibutytyl cyclic AMP also suggests an influence on enzymatic regulation of glucose metabolism.", "contents": "Effects of cyclic AMP and dibutyryl cyclic AMP on cerebral hemodynamics and metabolism in the baboon. Adenosine 3',5'-cycle monophosphate (cyclic AMP) (0.5 mg/kg) was infused into the carotid artery of baboons anesthesized with sodium pentobarbital, causing a biphasic increase in cerebral blood flow (CBF) and reduction in cerebrovascular resistance (CVR) associated in each phase with stimulation of cerebral metabolism evidenced by increased cerebral oxygen consumption (COMRO2) and cerebral glucose consumption (CMRG1). Intracarotid dibutyryl cyclic AMP (0.5 mg/kg) caused a monophasic increase in CBF and reduction of CVR but failed to alter cerebral metabolism. This may be due to its rapid removal from the circulation with ineffective passage across the blood-brain barrier since intracisternal infusion of dibutyryl cyclic AMP caused sustained increase in CBF, CMRO2 and CMRG1 and reduction in CVR. Intracarotid AMP (0.4 mg/kg) and adenosine (0.3 mg/kg) caused an immediate and more marked increase in CBF and decrease in CVR unassociated with cerebral metabolic change making it unlikely that the observed effects of cyclic AMP can be attributed to its breakdown products. Cyclic AMP or its dibutyryl derivative may alter cerebral metabolism secondary to neuronal activation but increase in glucose/oxygen utilization ratio after intracarotid cyclic AMP and intracisternal dibutytyl cyclic AMP also suggests an influence on enzymatic regulation of glucose metabolism."}
{"id": "PMID:191578", "title": "Radionuclide imaging, computed tomography, and gray-scale ultrasonography of the liver: a comparative study.", "content": "Transmission computed tomography (CT), gray-scale ultrasonography, and scinitillation-camera imaging were compared for detection of intrahepatic space-occupying processes. Fifty patients with suspected liver disease were studied by the three modalities. In the 35 cases with confirmed abnormalities, the madalities were rated on a scale of 0 to 5 in terms of their detection value; Each modality was found to have definite advantages and disadvantages. The mean score of ultrasound was highest (3.61), followed by nuclear medicine (3.11) and then CT (2.77). The combination of ultrasound and nuclear medicine identified all lesions, whereas CT alone or in combination with another technique occasionally failed to detect abnormal foci. In the future, the relative efficacy of these procedures may change with improved imaging technology and increased interpreter experience.", "contents": "Radionuclide imaging, computed tomography, and gray-scale ultrasonography of the liver: a comparative study. Transmission computed tomography (CT), gray-scale ultrasonography, and scinitillation-camera imaging were compared for detection of intrahepatic space-occupying processes. Fifty patients with suspected liver disease were studied by the three modalities. In the 35 cases with confirmed abnormalities, the madalities were rated on a scale of 0 to 5 in terms of their detection value; Each modality was found to have definite advantages and disadvantages. The mean score of ultrasound was highest (3.61), followed by nuclear medicine (3.11) and then CT (2.77). The combination of ultrasound and nuclear medicine identified all lesions, whereas CT alone or in combination with another technique occasionally failed to detect abnormal foci. In the future, the relative efficacy of these procedures may change with improved imaging technology and increased interpreter experience."}
{"id": "PMID:191579", "title": "Localization of 99mTc-Sn-pyrophosphate in left ventricular aneurysms.", "content": "Concentration of 99mTc-pyrophosphate (99mTc-PPi) in the area of left ventricular aneurysms is discussed. In three cases clinical, laboratory, and electrocardiographic (ECG) evidence did not indicate that these patients currently had an acute myocardial infarction, but each patient had a clinical history and an ECG picture compatible with an old myocardial infarction. Cardiac catheterization revealed a large left ventricular aneurysm in all three cases. The reason for the preferential uptake of the radionuclide in the area of these aneurysms is not certain at this time.", "contents": "Localization of 99mTc-Sn-pyrophosphate in left ventricular aneurysms. Concentration of 99mTc-pyrophosphate (99mTc-PPi) in the area of left ventricular aneurysms is discussed. In three cases clinical, laboratory, and electrocardiographic (ECG) evidence did not indicate that these patients currently had an acute myocardial infarction, but each patient had a clinical history and an ECG picture compatible with an old myocardial infarction. Cardiac catheterization revealed a large left ventricular aneurysm in all three cases. The reason for the preferential uptake of the radionuclide in the area of these aneurysms is not certain at this time."}
{"id": "PMID:191580", "title": "Renal displacement visualized on myocardial scintigram: case report.", "content": "Myocardial scinitgrams, using 99mTc-stannous pyrophosphate, showed an acute posterior infarction and an abnormally placed left kidney in a 24-year-old hypertensive man; Further study revealed that the kidney was displaced by a mass later proven to be a pheochromocytoma. The latter was the cause of his hypertension and probably instigated the acute myocardial infarction.", "contents": "Renal displacement visualized on myocardial scintigram: case report. Myocardial scinitgrams, using 99mTc-stannous pyrophosphate, showed an acute posterior infarction and an abnormally placed left kidney in a 24-year-old hypertensive man; Further study revealed that the kidney was displaced by a mass later proven to be a pheochromocytoma. The latter was the cause of his hypertension and probably instigated the acute myocardial infarction."}
{"id": "PMID:191581", "title": "Chick brain calcium binding protein: response to cholecalciferol and some developmental aspects.", "content": "Following oral administration of 3H-cholecalciferol to rachitic chicks, the radioactive metabolites found in brain tissues were separated by Sephadex LH-20 chromatography. The parent vitamins and two biologically important metabolites, 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol were detected in the brain, although at relatively low levels. A comparison with other tissues suggested the brain was much less permeable to the vitamin D steroids than were other tissues. However, chronic cholecalciferol administration for 4 weeks to severely vitamin D deficient chicks elicited a significant increase in the cerebellar content of a calcium-binding protein (CaBP). The lowest level administered, 2 IU/day (130 pmole), increased the CaBP content by more than 50%, while 16 IU/day (1.04 nmole) doubled the CaBP content. Chick brain CaBP has the same physical characteristics and is immunologically identical to the vitamin D-induced CaBP present in chick intestine, it differs in that single acute doses of vitamin D do not increase the content of brain CaBP while intestinal CaBP synthesis is stimulated significantly. The time course of appearance and content of brain CaBP in embryonic chicks was monitored. It was first detectable in the brain at day 15 of incubation and increased to a near post-hatch level by day 20. It differed in its initial time of appearance from both kidney CaBP which first appears at day 10 and intestinal CaBP which is not detectable until hatch day.", "contents": "Chick brain calcium binding protein: response to cholecalciferol and some developmental aspects. Following oral administration of 3H-cholecalciferol to rachitic chicks, the radioactive metabolites found in brain tissues were separated by Sephadex LH-20 chromatography. The parent vitamins and two biologically important metabolites, 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol were detected in the brain, although at relatively low levels. A comparison with other tissues suggested the brain was much less permeable to the vitamin D steroids than were other tissues. However, chronic cholecalciferol administration for 4 weeks to severely vitamin D deficient chicks elicited a significant increase in the cerebellar content of a calcium-binding protein (CaBP). The lowest level administered, 2 IU/day (130 pmole), increased the CaBP content by more than 50%, while 16 IU/day (1.04 nmole) doubled the CaBP content. Chick brain CaBP has the same physical characteristics and is immunologically identical to the vitamin D-induced CaBP present in chick intestine, it differs in that single acute doses of vitamin D do not increase the content of brain CaBP while intestinal CaBP synthesis is stimulated significantly. The time course of appearance and content of brain CaBP in embryonic chicks was monitored. It was first detectable in the brain at day 15 of incubation and increased to a near post-hatch level by day 20. It differed in its initial time of appearance from both kidney CaBP which first appears at day 10 and intestinal CaBP which is not detectable until hatch day."}
{"id": "PMID:191582", "title": "Changes in plasma 25-hydroxycholecalciferol and selected blood parameters after injection of massive doses of cholecalciferol or 25-hydroxycholecalciferol in non-lactating dairy cows.", "content": "Plasma levels of 25-hydroxycholecalciferol, free hydroxyproline, calcium, phosphorus, and magnesium were determined in non-lactating, pregnant dairy cows injected intra-muscularly with 15 X 10(6) IU of cholecalciferol or 25 mg of 25-hydroxycholecalciferol. A lag in the conversion of cholecalciferol to 25-hydroxycholecalciferol was observed in the cows injected with cholecalciferol, while an immediate increase was observed when cows were injected with 25-hydroxycholecalciferol directly. The increased plasma levels of 25-hydroxycholecalciferol following injection of cholecalciferol were directly related to rises in plasma free hydroxy-proline, calcium, and phosphorus, while plasma magnesium was inversely related to plasma 25-hydroxycholecalciferol. Injection of 25-hydroxycholecalciferol caused an immediate increase in plasma calcium which persisted for the duration of the experiment. The biological half-life of 25-hydroxycholecalciferol in the injected cows was found to be 34 days. The data indicate the possibility of a feedback mechanism in which massive doses of cholecalciferol inhibit hydroxylation at the 25ths carbon preventing its conversion to 25-hydroxycholecalciferol until after 8 days post injection. The increase in plasma 25-hydroxycholecalciferol after 8 days  resulted in increased bone resorption as indicated by plasma free hydroxyproline.", "contents": "Changes in plasma 25-hydroxycholecalciferol and selected blood parameters after injection of massive doses of cholecalciferol or 25-hydroxycholecalciferol in non-lactating dairy cows. Plasma levels of 25-hydroxycholecalciferol, free hydroxyproline, calcium, phosphorus, and magnesium were determined in non-lactating, pregnant dairy cows injected intra-muscularly with 15 X 10(6) IU of cholecalciferol or 25 mg of 25-hydroxycholecalciferol. A lag in the conversion of cholecalciferol to 25-hydroxycholecalciferol was observed in the cows injected with cholecalciferol, while an immediate increase was observed when cows were injected with 25-hydroxycholecalciferol directly. The increased plasma levels of 25-hydroxycholecalciferol following injection of cholecalciferol were directly related to rises in plasma free hydroxy-proline, calcium, and phosphorus, while plasma magnesium was inversely related to plasma 25-hydroxycholecalciferol. Injection of 25-hydroxycholecalciferol caused an immediate increase in plasma calcium which persisted for the duration of the experiment. The biological half-life of 25-hydroxycholecalciferol in the injected cows was found to be 34 days. The data indicate the possibility of a feedback mechanism in which massive doses of cholecalciferol inhibit hydroxylation at the 25ths carbon preventing its conversion to 25-hydroxycholecalciferol until after 8 days post injection. The increase in plasma 25-hydroxycholecalciferol after 8 days  resulted in increased bone resorption as indicated by plasma free hydroxyproline."}
{"id": "PMID:191584", "title": "The carbohydrate metabolism of Brugia pahangi microfilariae.", "content": "Evidence is presented that the microfilariae of Litomosoides carinii, Dipetalonema viteae and Brugia pahangi have an aerobic requirement for motility, but possibly not for survival. In addition, the data suggest that in an in vitro anaerobic environment, B. pahangi microfilariae ferment glucose only as far as lactate. In an aerobic environment, however, the data are consistent with a portion of glucose being dissimilated via a one step oxidative decarboxylation of pyruvate formed from glycolysis to acetate and CO2. In addition, a low level of complete oxidation, possibly via a tricarboxylic acid cycle pathway, may be occurring. Finally, if B. pahangi microfilariae are immobilized with levamisole in an aerobic atmosphere, the drug appears to alter the aerobic glucose metabolism of the parasite both qualitatively and quantitatively. A decreased glucose utilization occurs, together with a shift to a more nearly homolactate fermentation. It is suggested that the effects of levamisole on the metabolism of the microfilariid are secondary to the observed paralysis.", "contents": "The carbohydrate metabolism of Brugia pahangi microfilariae. Evidence is presented that the microfilariae of Litomosoides carinii, Dipetalonema viteae and Brugia pahangi have an aerobic requirement for motility, but possibly not for survival. In addition, the data suggest that in an in vitro anaerobic environment, B. pahangi microfilariae ferment glucose only as far as lactate. In an aerobic environment, however, the data are consistent with a portion of glucose being dissimilated via a one step oxidative decarboxylation of pyruvate formed from glycolysis to acetate and CO2. In addition, a low level of complete oxidation, possibly via a tricarboxylic acid cycle pathway, may be occurring. Finally, if B. pahangi microfilariae are immobilized with levamisole in an aerobic atmosphere, the drug appears to alter the aerobic glucose metabolism of the parasite both qualitatively and quantitatively. A decreased glucose utilization occurs, together with a shift to a more nearly homolactate fermentation. It is suggested that the effects of levamisole on the metabolism of the microfilariid are secondary to the observed paralysis."}
{"id": "PMID:191586", "title": "Diagnostic and operative problems in multiple pheochromocytomas.", "content": "Two children, aged 14 yr, with multiple pheochromocytomas are presented. Both patients had a positive family history. In the preoperative aortographies the intra-adrenal pheochromocytomas of both patients were well visualized, but not the extra-adrenal tumors of the first case. Chlorpromazine as an adrenergic blocking agent was successfully used in the preoperative treatment. Postoperative catecholamine excretion in the first case was repeatedly slightly increased indicating residual pheochromocytoma. In addition to the bilateral adrenal pheochromocytomas, multiple islet cell adrenomas and cholecystolithiasis were revealed at the operation of the second case. After bilateral adrenalectomy and total pancreaticoduodenectomy, regular follow-up examinations were carried out for 28 months. Hyperparathyroidism and signs of possible medullary thryoid carcinoma were discovered. Thus the patient had an unique pattern of MEA syndrome.", "contents": "Diagnostic and operative problems in multiple pheochromocytomas. Two children, aged 14 yr, with multiple pheochromocytomas are presented. Both patients had a positive family history. In the preoperative aortographies the intra-adrenal pheochromocytomas of both patients were well visualized, but not the extra-adrenal tumors of the first case. Chlorpromazine as an adrenergic blocking agent was successfully used in the preoperative treatment. Postoperative catecholamine excretion in the first case was repeatedly slightly increased indicating residual pheochromocytoma. In addition to the bilateral adrenal pheochromocytomas, multiple islet cell adrenomas and cholecystolithiasis were revealed at the operation of the second case. After bilateral adrenalectomy and total pancreaticoduodenectomy, regular follow-up examinations were carried out for 28 months. Hyperparathyroidism and signs of possible medullary thryoid carcinoma were discovered. Thus the patient had an unique pattern of MEA syndrome."}
{"id": "PMID:191587", "title": "Determination of porosity and pore-size distribution of aspirin tablets relevant to drug stability.", "content": "Total porosity and pore-size distribution of aspirin tablets prepared from aspirin, starch USP, and precipitated colloidal silicon dioxide were determined using mercury porosimetry. The model represented a hydrolyzable drug substance in combination with simple excipients. The role of starch and silicon dioxide on the microstructure of the tablets was investigated, as was the chemical stability of various systems. In general, the porosity of tablets containing a constant quantity of starch increased linearly with silicon dioxide concentration. Examination of the pore-size distribution, however, revealed that a low concentrations silicon dioxide functioned primarily to reduce the size and volume of coarse pores representing the spaces between the agglomerates of starch and aspirin particles. This effect was optimum at 3%. A further increase in silicon dioxide concentration produced tablets with relatively larger pore sizes. Studies of changes in the porosity characteristics of tablets as influenced by water vapor over time showed distinct differences in this complex parameter. A unique trend in the change of the pore-size distribution was noted with tablets containing 3% silicon dioxide. These observations are discussed relative to the stability of aspirin tablets in which this concentration of silicon dioxide produced a maximum stabilizing effect.", "contents": "Determination of porosity and pore-size distribution of aspirin tablets relevant to drug stability. Total porosity and pore-size distribution of aspirin tablets prepared from aspirin, starch USP, and precipitated colloidal silicon dioxide were determined using mercury porosimetry. The model represented a hydrolyzable drug substance in combination with simple excipients. The role of starch and silicon dioxide on the microstructure of the tablets was investigated, as was the chemical stability of various systems. In general, the porosity of tablets containing a constant quantity of starch increased linearly with silicon dioxide concentration. Examination of the pore-size distribution, however, revealed that a low concentrations silicon dioxide functioned primarily to reduce the size and volume of coarse pores representing the spaces between the agglomerates of starch and aspirin particles. This effect was optimum at 3%. A further increase in silicon dioxide concentration produced tablets with relatively larger pore sizes. Studies of changes in the porosity characteristics of tablets as influenced by water vapor over time showed distinct differences in this complex parameter. A unique trend in the change of the pore-size distribution was noted with tablets containing 3% silicon dioxide. These observations are discussed relative to the stability of aspirin tablets in which this concentration of silicon dioxide produced a maximum stabilizing effect."}
{"id": "PMID:191589", "title": "Phenobarbital actions in vivo: effects on extra cellular potassium activity and oxidative metabolism in cat cerebral cortex.", "content": "Extracellular potassium activity and changes in the reduction levels of intramitochondrial pyridine nucleotide (NAD) and cytochrome-a,a3 were monitored in the cerebral cortex of cats at rest and during electrical stimulation, before and after administration of sodium phenobarbital. Stimulation of the cortical surface evoked a transient increase in the level of oxidized NAD which was proportional in magnitude to the associated transient elevation of extracellular potassium. Phenobarbital (i.v.) produced, within minutes, a persistent shift in NAD to a more reduced level indicative of decreased oxygen consumption. Electrical excitability of the cortex also decreased within minutes, although there was no concomitant change in the resting extracellular potassium activity. Cortical stimulation produced transient elevations of [K+]0 and NADH oxidation and these responses returned to base lines more slowly following the barbiturate administration. However, the proportionality between NADH oxidation and [K+]0 elevation was not altered by phenobarbital. The kinetics of the cytochrome-a, a3 response to cortical stimulation mirrored those of NADH, implying that phenobarbital was not blocking electron transport in the respiratory chain between NADH and cytochrome-a, a3 even at doses where \"resting\" tissue oxygen consumption was decreased. The prolongation of recovery metabolism following phenobarbital was interpreted as being the result of protracted elevation of extracellular potassium activity. The slow return to \"resting\" levels of extracellular potassium is probably caused by interference with passive clearance mechanisms.", "contents": "Phenobarbital actions in vivo: effects on extra cellular potassium activity and oxidative metabolism in cat cerebral cortex. Extracellular potassium activity and changes in the reduction levels of intramitochondrial pyridine nucleotide (NAD) and cytochrome-a,a3 were monitored in the cerebral cortex of cats at rest and during electrical stimulation, before and after administration of sodium phenobarbital. Stimulation of the cortical surface evoked a transient increase in the level of oxidized NAD which was proportional in magnitude to the associated transient elevation of extracellular potassium. Phenobarbital (i.v.) produced, within minutes, a persistent shift in NAD to a more reduced level indicative of decreased oxygen consumption. Electrical excitability of the cortex also decreased within minutes, although there was no concomitant change in the resting extracellular potassium activity. Cortical stimulation produced transient elevations of [K+]0 and NADH oxidation and these responses returned to base lines more slowly following the barbiturate administration. However, the proportionality between NADH oxidation and [K+]0 elevation was not altered by phenobarbital. The kinetics of the cytochrome-a, a3 response to cortical stimulation mirrored those of NADH, implying that phenobarbital was not blocking electron transport in the respiratory chain between NADH and cytochrome-a, a3 even at doses where \"resting\" tissue oxygen consumption was decreased. The prolongation of recovery metabolism following phenobarbital was interpreted as being the result of protracted elevation of extracellular potassium activity. The slow return to \"resting\" levels of extracellular potassium is probably caused by interference with passive clearance mechanisms."}
{"id": "PMID:191585", "title": "Mixed lacrimal gland tumor arising from ectopic lacrimal gland tissue in the orbit.", "content": "An unusual case of lacrimal gland tumor from ectopic lacrimal gland tissue was presented and discussed. Grossly, the tumor was encapsulated and a distinct entity from the surrounding tissues. There were no connections to the lacimal gland and the tumor histologically appeared to be totally encapsulated even though some areas revealed early invasion. The location of the tumor in the orbit was unique, particularly in lieu of its histology, being located nasally and superiorly. A new and rare addition is now added to the differential diagnosis of unilateral exophthalmos.", "contents": "Mixed lacrimal gland tumor arising from ectopic lacrimal gland tissue in the orbit. An unusual case of lacrimal gland tumor from ectopic lacrimal gland tissue was presented and discussed. Grossly, the tumor was encapsulated and a distinct entity from the surrounding tissues. There were no connections to the lacimal gland and the tumor histologically appeared to be totally encapsulated even though some areas revealed early invasion. The location of the tumor in the orbit was unique, particularly in lieu of its histology, being located nasally and superiorly. A new and rare addition is now added to the differential diagnosis of unilateral exophthalmos."}
{"id": "PMID:191590", "title": "The effects of neomycin upon transmitter release and action.", "content": "These experiments were designed to determine the site and mechanism of action of neomycin on cholinergic transmission. These agents depressed the response of rat diaphragm preparations to phrenic nerve stimulation and to injected acetylcholine (ACh); however, equi-effective neuromuscular blocking concentrations of neomycin (6 x 10(-4) M), streptomycin (1.2 x 10(-3) M) or d-tubocurarine (6.5 x 10(-7) M) reduced the muscle response to injected ACh to 54,27 and 15% of control, respectively, suggesting that neomycin and streptomycin have a presynaptic effect. This finding was confirmed by measuring ACh release from the diaphragm during phrenic nerve stimulation; neomycin (6x10(-4) M) and streptomycin (1.2 x 10(-4) M) depressed ACh release to 29 and 41% of control, respectively. In the cat superior cervical ganglion neomycin (2 x 10(-3) M) blocked ganglionic transmission, did not reduce the response of ganglion cells to injected nicotine and depressed ACh release during preganglionic nerve stimulation to 61% of control in normal Ca++ (2.5 mM) medium and to less than 10% of control in low Ca++ (0.5 mM) medium. The increased accululation of 45Ca induced in rat isolated ganglia by preganglionic nerve stimulation was not changed by d-tubocurarine (2 x 10(-4) M), but was abolished by neomycin (2 x10(-3) M). It is concluded that neomycin blocks ACh release by blocking the influx of Ca++ necessary for transmitter release. This conclusion suggested that neomycin should block noradrenaline release, and this was shown using the anococcygeus preparation from the rat.", "contents": "The effects of neomycin upon transmitter release and action. These experiments were designed to determine the site and mechanism of action of neomycin on cholinergic transmission. These agents depressed the response of rat diaphragm preparations to phrenic nerve stimulation and to injected acetylcholine (ACh); however, equi-effective neuromuscular blocking concentrations of neomycin (6 x 10(-4) M), streptomycin (1.2 x 10(-3) M) or d-tubocurarine (6.5 x 10(-7) M) reduced the muscle response to injected ACh to 54,27 and 15% of control, respectively, suggesting that neomycin and streptomycin have a presynaptic effect. This finding was confirmed by measuring ACh release from the diaphragm during phrenic nerve stimulation; neomycin (6x10(-4) M) and streptomycin (1.2 x 10(-4) M) depressed ACh release to 29 and 41% of control, respectively. In the cat superior cervical ganglion neomycin (2 x 10(-3) M) blocked ganglionic transmission, did not reduce the response of ganglion cells to injected nicotine and depressed ACh release during preganglionic nerve stimulation to 61% of control in normal Ca++ (2.5 mM) medium and to less than 10% of control in low Ca++ (0.5 mM) medium. The increased accululation of 45Ca induced in rat isolated ganglia by preganglionic nerve stimulation was not changed by d-tubocurarine (2 x 10(-4) M), but was abolished by neomycin (2 x10(-3) M). It is concluded that neomycin blocks ACh release by blocking the influx of Ca++ necessary for transmitter release. This conclusion suggested that neomycin should block noradrenaline release, and this was shown using the anococcygeus preparation from the rat."}
{"id": "PMID:191591", "title": "Norepinephrine- and isoproterenol- induced changes in cardiac contractility and cyclic adenosine 3':5' -monophosphate levels during early development of the embryonic chick.", "content": "Changes in contractility and cyclic adenosine 3':5'-monophosphate (cAMP) levels in response to norepinephrine and isoproterenol were monitored in isolated 4-day-old (noninnervated) and 7-day-old (innervated) embryonic hearts to determine whether a relationship between beta adrenergic receptor, adenylate cyclase and altered cardiac function is established at a very early stage in embryonic development before innervation takes place. Norepinephrine and isoproterenol promoted rapid time- and dose-dependent rises in cAMP levels which were greater in the 4-day-old hearts. These increases paralleled observed functional alterations within a specific range of drug concentrations and time. The elevation of cAMP levels and effect on cardiac function produced by isoproterenol (10(-7)M) were blocked by propranolol (10(-6)M). Dissociations between changes in tissue cAMP levels and cardiac function were also uncovered. Maximal increases in contractility were achieved with lower drug concentrations than were required to promote maximal accumulation of cAMP. Relatively high concentrations of norepinephrine or isoproterenol were less effective than lower concentrations in stimulating contractility but were more effective in promoting cAMP accumulation, The results indicate that both cardiac beta receptors adenylate cyclase are present and functionally related early in embryogenesis before sympathetic innervation occurs and that cAMP accumulation is associated with modulation of contractile activity whithin a certain concentration range and time course.", "contents": "Norepinephrine- and isoproterenol- induced changes in cardiac contractility and cyclic adenosine 3':5' -monophosphate levels during early development of the embryonic chick. Changes in contractility and cyclic adenosine 3':5'-monophosphate (cAMP) levels in response to norepinephrine and isoproterenol were monitored in isolated 4-day-old (noninnervated) and 7-day-old (innervated) embryonic hearts to determine whether a relationship between beta adrenergic receptor, adenylate cyclase and altered cardiac function is established at a very early stage in embryonic development before innervation takes place. Norepinephrine and isoproterenol promoted rapid time- and dose-dependent rises in cAMP levels which were greater in the 4-day-old hearts. These increases paralleled observed functional alterations within a specific range of drug concentrations and time. The elevation of cAMP levels and effect on cardiac function produced by isoproterenol (10(-7)M) were blocked by propranolol (10(-6)M). Dissociations between changes in tissue cAMP levels and cardiac function were also uncovered. Maximal increases in contractility were achieved with lower drug concentrations than were required to promote maximal accumulation of cAMP. Relatively high concentrations of norepinephrine or isoproterenol were less effective than lower concentrations in stimulating contractility but were more effective in promoting cAMP accumulation, The results indicate that both cardiac beta receptors adenylate cyclase are present and functionally related early in embryogenesis before sympathetic innervation occurs and that cAMP accumulation is associated with modulation of contractile activity whithin a certain concentration range and time course."}
{"id": "PMID:191592", "title": "Metabolite studies of methamphetamine effects based upon mitochondrial respiratiory state in rat brain.", "content": "Methamphetamine-induced changes in metabolite levels were studied based upon a new approach to tissue sampling. In this procedure, the noninvasive, autoindicated redox state of intramitochondrial NADH was used to determine the point at which samples were taken rather than the time after drug injection. By this combination of in situ microfluorometry and tissue assay, a complex sequence of rapid changes in cerebral intermediary metabolism and associated mitochondrial redox shifts were observed. These changes were found to occur over a wide range of time course among animals after drug administration, and this temporal variation in response to the drug may be the factor for previously reported inconsistencies in metabolite patterns after methamphetamine. This finding emphasizes the potential difficulties that temporal variability produces in certain cerebral pharmacological responses and the value of the noninvasive, autoindicated redox keyed technique (NARK analysis) for metabolite sampling.", "contents": "Metabolite studies of methamphetamine effects based upon mitochondrial respiratiory state in rat brain. Methamphetamine-induced changes in metabolite levels were studied based upon a new approach to tissue sampling. In this procedure, the noninvasive, autoindicated redox state of intramitochondrial NADH was used to determine the point at which samples were taken rather than the time after drug injection. By this combination of in situ microfluorometry and tissue assay, a complex sequence of rapid changes in cerebral intermediary metabolism and associated mitochondrial redox shifts were observed. These changes were found to occur over a wide range of time course among animals after drug administration, and this temporal variation in response to the drug may be the factor for previously reported inconsistencies in metabolite patterns after methamphetamine. This finding emphasizes the potential difficulties that temporal variability produces in certain cerebral pharmacological responses and the value of the noninvasive, autoindicated redox keyed technique (NARK analysis) for metabolite sampling."}
{"id": "PMID:191593", "title": "The influence of ketamine on inotropic and chronotropic responsiveness of heart muscle.", "content": "The influence of ketamine on the inotropic and chronotropic responsiveness of heart muscle was examined in spontaneously beating right atrial preparations and in electrically driven left atrial preparations of guinea pigs. Ketamine (2.63 X 10(-5) to 4.2 X 10(-4) M) decreased heart rate of right atria and decreased contractile tension and its maximum rate of increase in both right and left atrial preparations (right atria greater than left atria). Ketamine did not prevent the heart rate increase produced by norepinephrine (NE; 1 X 10(-8) to 1 X 10(-4) M) in right atria; however, the maximum heart rate was consistently lower in ketamine-treated than in control muscles even after exposure to NE. Although contractile tension was decreased by ketamine, the maximum inotropic response to NE was consistently greater in ketamine-treated atria than in control atria. An inhibitor of the slow Ca++ current in heart muscle, D600, depressed the contractile effects of NE but did not prevent the positive inotropic interaction of ketamine and NE. Ketamine similarly enhanced the inotropic responses to norepinephrine (1 X 10(-6) M), epinephrine (1 X 10(-6) M), isoproterenol (1 X 10(-7) M) and dibutyryl cyclic adenosine 3':5'-monophosphate (AMP; 4 X 10(-3) M) in left atria electrically paced at a constant frequency of contraction of 1 Hz; however, ketamine inhibited the positive inotropic response to increased frequency of stimulation (0.1-3.0 Hz) and to ouabain (3 X 10(-7) M). These findings demonstrate that ketamine can exert a selective positive inotropic influence in heart muscle independent of heart rate or direct or reflexogenic autonomic nervous system changes, and suggest that this activity could in some way be associated with an alteration of the intracellular disposition of cyclic AMP.", "contents": "The influence of ketamine on inotropic and chronotropic responsiveness of heart muscle. The influence of ketamine on the inotropic and chronotropic responsiveness of heart muscle was examined in spontaneously beating right atrial preparations and in electrically driven left atrial preparations of guinea pigs. Ketamine (2.63 X 10(-5) to 4.2 X 10(-4) M) decreased heart rate of right atria and decreased contractile tension and its maximum rate of increase in both right and left atrial preparations (right atria greater than left atria). Ketamine did not prevent the heart rate increase produced by norepinephrine (NE; 1 X 10(-8) to 1 X 10(-4) M) in right atria; however, the maximum heart rate was consistently lower in ketamine-treated than in control muscles even after exposure to NE. Although contractile tension was decreased by ketamine, the maximum inotropic response to NE was consistently greater in ketamine-treated atria than in control atria. An inhibitor of the slow Ca++ current in heart muscle, D600, depressed the contractile effects of NE but did not prevent the positive inotropic interaction of ketamine and NE. Ketamine similarly enhanced the inotropic responses to norepinephrine (1 X 10(-6) M), epinephrine (1 X 10(-6) M), isoproterenol (1 X 10(-7) M) and dibutyryl cyclic adenosine 3':5'-monophosphate (AMP; 4 X 10(-3) M) in left atria electrically paced at a constant frequency of contraction of 1 Hz; however, ketamine inhibited the positive inotropic response to increased frequency of stimulation (0.1-3.0 Hz) and to ouabain (3 X 10(-7) M). These findings demonstrate that ketamine can exert a selective positive inotropic influence in heart muscle independent of heart rate or direct or reflexogenic autonomic nervous system changes, and suggest that this activity could in some way be associated with an alteration of the intracellular disposition of cyclic AMP."}
{"id": "PMID:191594", "title": "Cytotoxicity of ricinoleic acid (castor oil) and other intestinal secretagogues on isolated intestinal epithelial cells.", "content": "Epithelial cells were isolated from hamster small intestine by a technique of vibration and used to measure cytotoxicity in vitro of certain substances known to stimulate intestinal fluid secretion. These secretagogues have laxative properties and produce mucosal damage in vivo. Compounds tested were ricinoleic acid (caster oil), dioctyl sodium sulfosuccinate, oleic acid, sodium deoxycholate and sodium cholate. Cytotoxicity was assessed by: 1) exclusion of trypan blue; 2) release of intracellular (prelabeled) 51Cr; and 3) inhibition of cellular uptake of 3-O-methylglucose. Ricinoleate produced a dose-dependent (0.1-2.0 mM) cytotoxicity as assessed by all three methods. Oleic acid, a nonhydroxylated analog of ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate but its trihydroxy congener, cholate, was less potent. Dioctyl sodium sulfosuccinate had cytotoxicity similar in magnitude to that of ricinoleate and deoxycholate. Cytotoxicity of these agents to isolated cells may relate to their secretory potential in vivo, their abilities to produce structural change at the mucosal surface and their laxative properties.", "contents": "Cytotoxicity of ricinoleic acid (castor oil) and other intestinal secretagogues on isolated intestinal epithelial cells. Epithelial cells were isolated from hamster small intestine by a technique of vibration and used to measure cytotoxicity in vitro of certain substances known to stimulate intestinal fluid secretion. These secretagogues have laxative properties and produce mucosal damage in vivo. Compounds tested were ricinoleic acid (caster oil), dioctyl sodium sulfosuccinate, oleic acid, sodium deoxycholate and sodium cholate. Cytotoxicity was assessed by: 1) exclusion of trypan blue; 2) release of intracellular (prelabeled) 51Cr; and 3) inhibition of cellular uptake of 3-O-methylglucose. Ricinoleate produced a dose-dependent (0.1-2.0 mM) cytotoxicity as assessed by all three methods. Oleic acid, a nonhydroxylated analog of ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate but its trihydroxy congener, cholate, was less potent. Dioctyl sodium sulfosuccinate had cytotoxicity similar in magnitude to that of ricinoleate and deoxycholate. Cytotoxicity of these agents to isolated cells may relate to their secretory potential in vivo, their abilities to produce structural change at the mucosal surface and their laxative properties."}
{"id": "PMID:191595", "title": "Secretion of fluid and amylase in the perfused rat pancreas.", "content": "1. The isolated rat pancreas was perfused with physiological salt solutions of varying composition. Flow of pancreatic juice and output of amylase during rest and after stimulation with pure secretin, pure cholecystokinin-pancreozymin (CCK-PZ), caerulein or acetylcholine (ACh) were measured. 2. Basal fluid secretion was abolished replacing perfusion fluid NA+ or Cl- by Tris+ or SO42- respectively. Readmission of Na+ or Cl- caused a transient increase above the normal control level of both fluid and amylase output. Exposure to K+-free solution severely reduced fluid output and K+ readmission resulted in a transient increase in secretory rate. 3. Maximal stimulation with ACh (10(-7) M), CCK-PZ (1-5 X 10(-10) M) or caerulein (10(-10) M) caused marked sustained fluid and amylase secretion. Maximal secretin stimulation (5-7 X 10(-9) M) caused marked sustained fluid but only a small sustained amylase secretion following an initial transient. 4. Under continuous secretin stimulation, replacement of the CO2/HCO3-buffered control fluid by a CO2/HCO3-free Tris buffered solution caused a sharp decrease in pancreatic juice flow. In the absence of extracellular CO2/HCO3-secretin did not evoke fluid or enzyme secretion. In contrast the effects of ACh, CCK-PZ or caerulein were independent on CO2/HCO3-. Monobutyryl cyclic AMP (10(-3) M) caused marked sustained fluid secretion and transient enzyme secretion. The effect was entirely dependent on the presence of CO2/HCO3-in the perfusion fluid. 5. Ouabain (10(-4)-10(-3) M) markedly inhibited both secretin- and caerulein-evoked fluid secretion while caerulein-evoked amylase secretion was hardly affected. Similar findings were made with K+-free solution. 6. The effect of maximal secretin stimulation on amylase secretion was greatly augmented in the presence of a maximally stimulating concentration of caerulein. The effects on fluid secretion of secretin and caerulein were simply additive. The effects of secretin on both amylase and fluid secretion, in the presence of caerulein, were entirely dependent on the presence of CO2/HCO3- in the perfusion fluid. 7. We conclude that two different fluid secretion processes occur in the rat exocrine pancreas. One stimulated by ACh and CCK-PZ, that is independent of extracellular CO2/HCO3- and another stimulated by secretin involving H+ or HCO3-transport. Only the effects of secretin seem to be mediated by intracellular cyclic AMP.", "contents": "Secretion of fluid and amylase in the perfused rat pancreas. 1. The isolated rat pancreas was perfused with physiological salt solutions of varying composition. Flow of pancreatic juice and output of amylase during rest and after stimulation with pure secretin, pure cholecystokinin-pancreozymin (CCK-PZ), caerulein or acetylcholine (ACh) were measured. 2. Basal fluid secretion was abolished replacing perfusion fluid NA+ or Cl- by Tris+ or SO42- respectively. Readmission of Na+ or Cl- caused a transient increase above the normal control level of both fluid and amylase output. Exposure to K+-free solution severely reduced fluid output and K+ readmission resulted in a transient increase in secretory rate. 3. Maximal stimulation with ACh (10(-7) M), CCK-PZ (1-5 X 10(-10) M) or caerulein (10(-10) M) caused marked sustained fluid and amylase secretion. Maximal secretin stimulation (5-7 X 10(-9) M) caused marked sustained fluid but only a small sustained amylase secretion following an initial transient. 4. Under continuous secretin stimulation, replacement of the CO2/HCO3-buffered control fluid by a CO2/HCO3-free Tris buffered solution caused a sharp decrease in pancreatic juice flow. In the absence of extracellular CO2/HCO3-secretin did not evoke fluid or enzyme secretion. In contrast the effects of ACh, CCK-PZ or caerulein were independent on CO2/HCO3-. Monobutyryl cyclic AMP (10(-3) M) caused marked sustained fluid secretion and transient enzyme secretion. The effect was entirely dependent on the presence of CO2/HCO3-in the perfusion fluid. 5. Ouabain (10(-4)-10(-3) M) markedly inhibited both secretin- and caerulein-evoked fluid secretion while caerulein-evoked amylase secretion was hardly affected. Similar findings were made with K+-free solution. 6. The effect of maximal secretin stimulation on amylase secretion was greatly augmented in the presence of a maximally stimulating concentration of caerulein. The effects on fluid secretion of secretin and caerulein were simply additive. The effects of secretin on both amylase and fluid secretion, in the presence of caerulein, were entirely dependent on the presence of CO2/HCO3- in the perfusion fluid. 7. We conclude that two different fluid secretion processes occur in the rat exocrine pancreas. One stimulated by ACh and CCK-PZ, that is independent of extracellular CO2/HCO3- and another stimulated by secretin involving H+ or HCO3-transport. Only the effects of secretin seem to be mediated by intracellular cyclic AMP."}
{"id": "PMID:191596", "title": "Rat adrenocortical dynamics.", "content": "1. The dynamics of the adrenocortical response to adrenocorticotrophic hormone (ACTH) was studied in anaesthetized, acutely hypophysectomized male rats. 2. ACTH test-signals were applied either in a jugular vein ('intact infused preparation') or in the aorta through the coeliac artery with the aorta ligated below this artery ('isolated in situ perfused preparation'). The adrenocortical responses were measured directly in samples serially taken from the left adrenal vein. 3. Tested ACTH signals were either impulses (injections of 0-05--1-2 mu. ACTH) or step functions (constant infusions of 0-025--1-6 mu. ACTH/min). 4. All responses showed a 3-6 min delay, larger delays corresponding to smaller input signals. The step responses reached steady-state level without overshoot. 5. The impulse responses of the isolated perfused and of the intact infused glands, as well as their step responses, were similar as to dynamic form. 6. It is concluded that there is an inherent delay in the responses of both the isolated perfused and of the intact infused rat adrenal gland. Further, unlike what has been reported for the canine adrenal gland, the intact rat adrenal gland does not appear to be appreciably 'faster' in its response than the isolated gland. Finally, the amplification factor from ACTH to corticosterone could be estimated for both preparations in the case of ACTH injections; a value of 1-3 X 10(6) (one ACTH molecule activates synthesis and release of 1-3 million corticosterone molecules) was found.", "contents": "Rat adrenocortical dynamics. 1. The dynamics of the adrenocortical response to adrenocorticotrophic hormone (ACTH) was studied in anaesthetized, acutely hypophysectomized male rats. 2. ACTH test-signals were applied either in a jugular vein ('intact infused preparation') or in the aorta through the coeliac artery with the aorta ligated below this artery ('isolated in situ perfused preparation'). The adrenocortical responses were measured directly in samples serially taken from the left adrenal vein. 3. Tested ACTH signals were either impulses (injections of 0-05--1-2 mu. ACTH) or step functions (constant infusions of 0-025--1-6 mu. ACTH/min). 4. All responses showed a 3-6 min delay, larger delays corresponding to smaller input signals. The step responses reached steady-state level without overshoot. 5. The impulse responses of the isolated perfused and of the intact infused glands, as well as their step responses, were similar as to dynamic form. 6. It is concluded that there is an inherent delay in the responses of both the isolated perfused and of the intact infused rat adrenal gland. Further, unlike what has been reported for the canine adrenal gland, the intact rat adrenal gland does not appear to be appreciably 'faster' in its response than the isolated gland. Finally, the amplification factor from ACTH to corticosterone could be estimated for both preparations in the case of ACTH injections; a value of 1-3 X 10(6) (one ACTH molecule activates synthesis and release of 1-3 million corticosterone molecules) was found."}
{"id": "PMID:191597", "title": "The formation and regression of synapses during the re-innervation of axolotl striated muscles.", "content": "1. A study has been made of the formation and regression of synapses formed by spinal nerves 16 and 17 in axolotl hind-limb flexor muscles following the severing of nerve 16, using histological, ultrastructural and electrophysiological techniques. 2. Axolotl hind-limb flexor myofibres possessed 'en plaque' end-plates from either spinal nerve 16 or 17 or both at intervals of about 1000 micronm along their length; the myofibre's length constant was about 700 micronm allowing electrophysiological observations of at least two of these synapses during a single impalement; transmitter release at these synapses could be described by binomial statistics and in a given set of ionic conditions the binomial statistic parameter n was directly proportional to the size of the nerve terminals whilst the binomial statistic parameter p was invariant to changes in nerve terminal size. 3. The distribution of synapses formed by spinal nerves 16 and 17 in different sectors of the axolotl hind-limb flexor muscles was determined from a study of evoked end-plate potentials; the middle and proximal sectors of the flexor muscles contained myofibres which received an innervation from nerve 16 only, whereas the sectors surrounding these contained myofibres innervated either by nerve 16 or nerve 17 or by both nerves. 4. Six days following the severing of spinal nerve 16, evoked transmitter release from the synapses formed by this nerve had failed; transmission was subsequently recorded at a few synapses formed by nerve 17 in the middle and proximal sectors of the flexor muscles which are not normally innervated by this nerve and these synapses had a low n; during the succeeding four weeks the value of n at the synapses increased to a size about 70% that of the terminals normally formed by nerve 16 at these sites. 5. Four weeks after severing nerve 16, myofibres which possessed synapses formed by nerve 17 also possessed synapses from re-innervating nerve 16 and these were sometimes formed at the same synaptic sites as those occupied by nerve 17. 6. In the subsequent sixteen weeks, the n value of synapses formed by nerve 17 declined whilst the n values of synapses formed by re-innervating nerve 16 on the same myofibres matured to their control size. 7. It is suggested that on  severing nerve 16 collateral sprouting of nearby intact nerve 17 occurs and these collateral sprouts innervate the denervated synaptic sites, although the sprouts arenot as well matched to the denervated synaptic sites as are the original nerve terminals; thus if nerve 16 returns it preferentially forms synapses at its original synaptic sites, and the collateral synapses formed by nerve 17 regress.", "contents": "The formation and regression of synapses during the re-innervation of axolotl striated muscles. 1. A study has been made of the formation and regression of synapses formed by spinal nerves 16 and 17 in axolotl hind-limb flexor muscles following the severing of nerve 16, using histological, ultrastructural and electrophysiological techniques. 2. Axolotl hind-limb flexor myofibres possessed 'en plaque' end-plates from either spinal nerve 16 or 17 or both at intervals of about 1000 micronm along their length; the myofibre's length constant was about 700 micronm allowing electrophysiological observations of at least two of these synapses during a single impalement; transmitter release at these synapses could be described by binomial statistics and in a given set of ionic conditions the binomial statistic parameter n was directly proportional to the size of the nerve terminals whilst the binomial statistic parameter p was invariant to changes in nerve terminal size. 3. The distribution of synapses formed by spinal nerves 16 and 17 in different sectors of the axolotl hind-limb flexor muscles was determined from a study of evoked end-plate potentials; the middle and proximal sectors of the flexor muscles contained myofibres which received an innervation from nerve 16 only, whereas the sectors surrounding these contained myofibres innervated either by nerve 16 or nerve 17 or by both nerves. 4. Six days following the severing of spinal nerve 16, evoked transmitter release from the synapses formed by this nerve had failed; transmission was subsequently recorded at a few synapses formed by nerve 17 in the middle and proximal sectors of the flexor muscles which are not normally innervated by this nerve and these synapses had a low n; during the succeeding four weeks the value of n at the synapses increased to a size about 70% that of the terminals normally formed by nerve 16 at these sites. 5. Four weeks after severing nerve 16, myofibres which possessed synapses formed by nerve 17 also possessed synapses from re-innervating nerve 16 and these were sometimes formed at the same synaptic sites as those occupied by nerve 17. 6. In the subsequent sixteen weeks, the n value of synapses formed by nerve 17 declined whilst the n values of synapses formed by re-innervating nerve 16 on the same myofibres matured to their control size. 7. It is suggested that on  severing nerve 16 collateral sprouting of nearby intact nerve 17 occurs and these collateral sprouts innervate the denervated synaptic sites, although the sprouts arenot as well matched to the denervated synaptic sites as are the original nerve terminals; thus if nerve 16 returns it preferentially forms synapses at its original synaptic sites, and the collateral synapses formed by nerve 17 regress."}
{"id": "PMID:191598", "title": "A review of psychogenic aspects and treatment of bruxism.", "content": "The signs and symptoms of bruxism are detectable, but unfortunately, the hypothesized etiologies and mechanisms of their action have not been satisfactorily substantiated. 2. Researchers emphasize the significance of the oral cavity in expressing emotions and that occlusal adjustments and other mechanical types of treatment may be inadequate. 3. The treatment of bruxism involves the management of psychic tension, signs and symptoms, occlusal irritations, and neuromuscular habit patterns. 4. With the greater sophistication in the social sciences, therapy for bruxism in the future may become largely behavioral in nature, rather than mechanical.", "contents": "A review of psychogenic aspects and treatment of bruxism. The signs and symptoms of bruxism are detectable, but unfortunately, the hypothesized etiologies and mechanisms of their action have not been satisfactorily substantiated. 2. Researchers emphasize the significance of the oral cavity in expressing emotions and that occlusal adjustments and other mechanical types of treatment may be inadequate. 3. The treatment of bruxism involves the management of psychic tension, signs and symptoms, occlusal irritations, and neuromuscular habit patterns. 4. With the greater sophistication in the social sciences, therapy for bruxism in the future may become largely behavioral in nature, rather than mechanical."}
{"id": "PMID:191600", "title": "Family therapy: using a transactional approach.", "content": "The family can be viewed as a natural group which includes a mutual influence phenomenon. Intervention follows relationship building and assessment and is geared towards helping the family members challenge and change dysfunctional coding, decoding and structural transactions which inhibit the family group from meeting its idividual psychological needs.", "contents": "Family therapy: using a transactional approach. The family can be viewed as a natural group which includes a mutual influence phenomenon. Intervention follows relationship building and assessment and is geared towards helping the family members challenge and change dysfunctional coding, decoding and structural transactions which inhibit the family group from meeting its idividual psychological needs."}
{"id": "PMID:191604", "title": "Sequential changes associated with the degeneration of preovulatory rat follicles.", "content": "In 26-day-old rats, follicles capable of ovulation were present 48 h after PMSG injection and they degenerated if not exposed to an ovulating dose of HCG. In such follicles 125I-labelled LH bound to the thecal and granulosa cells. By 60 h after PMSG, LH binding to the granulosa cells was reduced by 46% although these follicles retained their ability to ovulate. LH binding to the granulosa cells was lost in most follicles by 72 h and ovulation could not be induced. The thecal cells still possessed LH binding sites at 72 h after PMSG. HCG stimulation of these follicles resulted in disruption of the granulosa and the invasion of blood cells into the antrum.", "contents": "Sequential changes associated with the degeneration of preovulatory rat follicles. In 26-day-old rats, follicles capable of ovulation were present 48 h after PMSG injection and they degenerated if not exposed to an ovulating dose of HCG. In such follicles 125I-labelled LH bound to the thecal and granulosa cells. By 60 h after PMSG, LH binding to the granulosa cells was reduced by 46% although these follicles retained their ability to ovulate. LH binding to the granulosa cells was lost in most follicles by 72 h and ovulation could not be induced. The thecal cells still possessed LH binding sites at 72 h after PMSG. HCG stimulation of these follicles resulted in disruption of the granulosa and the invasion of blood cells into the antrum."}
{"id": "PMID:191605", "title": "Studies on factors affecting release of gonadotrophins during the superfusion of isolated rat pituitaries.", "content": "Isolated pituitary glands from adult male rats were maintained in a continuous flow system. Gn-RH (1000 pmol/ml) caused a characteristic release of cyclic AMP, LH, and FSH. Cyclic AMP (1000 nmol/ml) liberated a similar amount of both gonadotrophins. Theophylline (1 mmol/ml) enhanced the effect of cyclic AMP by 21% for LH and 41% for FSH. The infusion of oestradiol (184 pmol/ml) alone or before Gn-RH infusion did not produce a significant effect on the secretion of either gonadotrophin or cyclic AMP. In contrast, there was a significant reduction in the amount of LH (P less than 0-025) and FSH (P less than 0-05) released by pituitaries infused with oestradiol and cyclic AMP.", "contents": "Studies on factors affecting release of gonadotrophins during the superfusion of isolated rat pituitaries. Isolated pituitary glands from adult male rats were maintained in a continuous flow system. Gn-RH (1000 pmol/ml) caused a characteristic release of cyclic AMP, LH, and FSH. Cyclic AMP (1000 nmol/ml) liberated a similar amount of both gonadotrophins. Theophylline (1 mmol/ml) enhanced the effect of cyclic AMP by 21% for LH and 41% for FSH. The infusion of oestradiol (184 pmol/ml) alone or before Gn-RH infusion did not produce a significant effect on the secretion of either gonadotrophin or cyclic AMP. In contrast, there was a significant reduction in the amount of LH (P less than 0-025) and FSH (P less than 0-05) released by pituitaries infused with oestradiol and cyclic AMP."}
{"id": "PMID:191609", "title": "99m Technetium-pyrophosphate scintiphotography in bone sarcoidosis.", "content": "Comparative studies between routine roentgenograms and scintiphotographs using 99mTc-pyrophosphate, of the hands and feet are documented in three cases of bone sarcoidosis. All the abnormal roentgenographic findings were also detected by 99mTc-pyrophosphate bone imaging. However, several areas of increased radiopharmaceutical uptake were found in areas with normal roentgenographic studies. These results suggest that the 99mTc-pyrophosphate bone scintiphotographs might be more sensitive than radiographs in the localization of the bone involvement in sarcoidosis.", "contents": "99m Technetium-pyrophosphate scintiphotography in bone sarcoidosis. Comparative studies between routine roentgenograms and scintiphotographs using 99mTc-pyrophosphate, of the hands and feet are documented in three cases of bone sarcoidosis. All the abnormal roentgenographic findings were also detected by 99mTc-pyrophosphate bone imaging. However, several areas of increased radiopharmaceutical uptake were found in areas with normal roentgenographic studies. These results suggest that the 99mTc-pyrophosphate bone scintiphotographs might be more sensitive than radiographs in the localization of the bone involvement in sarcoidosis."}
{"id": "PMID:191610", "title": "Bis-basic-substituted polycyclic aromatic compounds. A new class of antiviral agents. 8. Bis-basic derivatives of carbazole, dibenzofuran, and dibenzothiophene.", "content": "A series of bisalkamine esters, bis-basic ethers, and bis-basic ketones of carbazole, N-ethylcarbazole, dibenzofuran, and dibenzothiophene was synthesized and evaluated for antiviral activity. The series also included two bis-basic alkanes of N-ethylcarbazole and one bis-basic carboxamide of dibenzofuran. Structure-activity relationships indicated that within the carbazole and N-ethylcarbazole series the bisalkamine esters gave the most active derivatives while the bis-basic ketone derivatives of dibenzofuran and dibenzothiophene afforded the more potent compounds within the respective series. The [6,5,6]heterocyclic nuclei were compared with the [6,5,6] aromatic nuclei (fluroene and fluoren-9-one) including tilorone with respect to antiviral activity against encephalomyocarditis (EMC) virus. Maximum activity was associated with the bis-basic ketone side chain and fluoren-9-one nucleus.", "contents": "Bis-basic-substituted polycyclic aromatic compounds. A new class of antiviral agents. 8. Bis-basic derivatives of carbazole, dibenzofuran, and dibenzothiophene. A series of bisalkamine esters, bis-basic ethers, and bis-basic ketones of carbazole, N-ethylcarbazole, dibenzofuran, and dibenzothiophene was synthesized and evaluated for antiviral activity. The series also included two bis-basic alkanes of N-ethylcarbazole and one bis-basic carboxamide of dibenzofuran. Structure-activity relationships indicated that within the carbazole and N-ethylcarbazole series the bisalkamine esters gave the most active derivatives while the bis-basic ketone derivatives of dibenzofuran and dibenzothiophene afforded the more potent compounds within the respective series. The [6,5,6]heterocyclic nuclei were compared with the [6,5,6] aromatic nuclei (fluroene and fluoren-9-one) including tilorone with respect to antiviral activity against encephalomyocarditis (EMC) virus. Maximum activity was associated with the bis-basic ketone side chain and fluoren-9-one nucleus."}
{"id": "PMID:191611", "title": "2-Substituted derivatives of 9-alpha-D-arabinofuranosyladenine and 9-alpha-D-arabinofuranosyl-8-azaadenine.", "content": "2-Substituted derivatives of 9-alpha-D-arabinofuranosyladenine were prepared via the fusion of tetra-O-acetyl-alpha-D-arabinofuranose with 2,6-dichloropurine followed by stepwise displacement of the chloro groups. A different approach, the reaction of 2,3,5-tri-O-benzoly-D-arabinofuranosyl bromide with 2,6-bis(methylthio)-8-azapurine in refluxing toluene in the presence of molecular sieve followed by stepwise reaction of the blocked nucleoside with methanolic ammonia and then other nucleophiles, gave 2-substituted derivatives of 9-alpha-D-arabinofuranosyl-8-azaadenine; In contrast to the parent compounds, none of these 2-substituted derivatives showed significant antiviral activity.", "contents": "2-Substituted derivatives of 9-alpha-D-arabinofuranosyladenine and 9-alpha-D-arabinofuranosyl-8-azaadenine. 2-Substituted derivatives of 9-alpha-D-arabinofuranosyladenine were prepared via the fusion of tetra-O-acetyl-alpha-D-arabinofuranose with 2,6-dichloropurine followed by stepwise displacement of the chloro groups. A different approach, the reaction of 2,3,5-tri-O-benzoly-D-arabinofuranosyl bromide with 2,6-bis(methylthio)-8-azapurine in refluxing toluene in the presence of molecular sieve followed by stepwise reaction of the blocked nucleoside with methanolic ammonia and then other nucleophiles, gave 2-substituted derivatives of 9-alpha-D-arabinofuranosyl-8-azaadenine; In contrast to the parent compounds, none of these 2-substituted derivatives showed significant antiviral activity."}
{"id": "PMID:191612", "title": "Potential antitumor agents. 21. Dialkanolamine dialkanesulfonic esters.", "content": "Homologous dialkanesulfonic esters of 2,2'-iminodiethanol, 3,3'-iminodi-1-propanol, N-(2-hydroxyethyl)-6-amino-1-hexanol, and N-(3-hydroxypropyl)-6-amino-1-hexanol were prepared via the N-trityl derivatives and screened for L1210 activity. For each active agent significant increases in life-span in L1210 tests (ILS) were correlated by linear least-squares regression with the corresponding log doses. The maximum ILS, taken from this regression line at the determined LD10, was used as a quantitative measure of antileukemic effectivenss. Within each homologoud series log ILSmax could be correlated with a binomial expression in lipophilic-hydrophilic balance, as measured by Rm values, but all active members from the four series could not be successfully included in a single correlation. By modification of Rm values with an ionization factor, log (H+/H+ + Ka), all active compounds could then be included in a significant correlation equation.", "contents": "Potential antitumor agents. 21. Dialkanolamine dialkanesulfonic esters. Homologous dialkanesulfonic esters of 2,2'-iminodiethanol, 3,3'-iminodi-1-propanol, N-(2-hydroxyethyl)-6-amino-1-hexanol, and N-(3-hydroxypropyl)-6-amino-1-hexanol were prepared via the N-trityl derivatives and screened for L1210 activity. For each active agent significant increases in life-span in L1210 tests (ILS) were correlated by linear least-squares regression with the corresponding log doses. The maximum ILS, taken from this regression line at the determined LD10, was used as a quantitative measure of antileukemic effectivenss. Within each homologoud series log ILSmax could be correlated with a binomial expression in lipophilic-hydrophilic balance, as measured by Rm values, but all active members from the four series could not be successfully included in a single correlation. By modification of Rm values with an ionization factor, log (H+/H+ + Ka), all active compounds could then be included in a significant correlation equation."}
{"id": "PMID:191613", "title": "11,12-Secoprostaglandins. 3. 8-Alkylthio(sulfinyl and sulfonyl)-12-hydroxyalkanoic acids and related compounds.", "content": "A series of 8-alkylthio(sulfinyl and sulfonyl)-12-hydroxyalkanoic acids which embody structural features of 11,12-secoprostaglandins was synthesized and evaluated for their ability to mimic the E series prostaglandins in stimulating cAMP formation in the mouse ovary and in binding to the rat lipocyte prostaglandin receptor. A key member of the series, 8-methylsulfonyl-12-hydroxyheptadecanoic acid, markedly stimulated cAMP formation at reasonable pharmacological concentrations, shows significant affinity for a prostaglandin receptor, and effectively inhibits antigen-induced lymphocyte transformation. In contrast, this compound is not a substrate for 15-hydroxyprostaglandin dehydrogenase, the major prostaglandin-metabolizing enzyme.", "contents": "11,12-Secoprostaglandins. 3. 8-Alkylthio(sulfinyl and sulfonyl)-12-hydroxyalkanoic acids and related compounds. A series of 8-alkylthio(sulfinyl and sulfonyl)-12-hydroxyalkanoic acids which embody structural features of 11,12-secoprostaglandins was synthesized and evaluated for their ability to mimic the E series prostaglandins in stimulating cAMP formation in the mouse ovary and in binding to the rat lipocyte prostaglandin receptor. A key member of the series, 8-methylsulfonyl-12-hydroxyheptadecanoic acid, markedly stimulated cAMP formation at reasonable pharmacological concentrations, shows significant affinity for a prostaglandin receptor, and effectively inhibits antigen-induced lymphocyte transformation. In contrast, this compound is not a substrate for 15-hydroxyprostaglandin dehydrogenase, the major prostaglandin-metabolizing enzyme."}
{"id": "PMID:191614", "title": "Evidence for separate peptide sequences related to the lipolytic and magnesium-accumulating activities of ACTH. Analogy with adrenergic receptors.", "content": "Native adrenocorticotropin [ACTH-(1-39)] and ACTH-(1-24) stimulate both lipolysis and magnesium accumulation in rat adipocyte plasma membrane vesicles. ACTH-(1-20) retains full lipolytic activity but has a minimal effect on magnesium accumulation. In contrast ACTH-(11-24) stimulates magnesium accumulation but not lipolysis. These findings indicate that within the ACTH molecule the peptide sequence responsible for stimulation of magnesium accumulation is distinctly separate from the core sequence (residues 4-10) essential for stimulation of adenylyl cyclase activity and cAMP mediated lipolysis. Phentolamine, an alpha-adrenergic antagonist, blocks the bulk of magnesium accumulation stimulated by native ACTH and norepinephrine; propranolol, a beta-adrenergic antagonist, blocks the earliest phase of Mg2+ uptake by these hormones but has little effect on net uptake. Isoproterenol, a beta-adrenergic agonist, stimulates magnesium uptake only minimally. The pattern of uptake stimulated by methoxamine, an alpha-adrenergic agonist, or ACTH-(11-24) is quite similar to that produced by native ACTH in the presence of propranolol. The receptor through which ACTH mediates stimulation of the bulk of magnesium appears to be analogous to the alpha-adrenergic receptor through which norepinephrine stimulates this same process.", "contents": "Evidence for separate peptide sequences related to the lipolytic and magnesium-accumulating activities of ACTH. Analogy with adrenergic receptors. Native adrenocorticotropin [ACTH-(1-39)] and ACTH-(1-24) stimulate both lipolysis and magnesium accumulation in rat adipocyte plasma membrane vesicles. ACTH-(1-20) retains full lipolytic activity but has a minimal effect on magnesium accumulation. In contrast ACTH-(11-24) stimulates magnesium accumulation but not lipolysis. These findings indicate that within the ACTH molecule the peptide sequence responsible for stimulation of magnesium accumulation is distinctly separate from the core sequence (residues 4-10) essential for stimulation of adenylyl cyclase activity and cAMP mediated lipolysis. Phentolamine, an alpha-adrenergic antagonist, blocks the bulk of magnesium accumulation stimulated by native ACTH and norepinephrine; propranolol, a beta-adrenergic antagonist, blocks the earliest phase of Mg2+ uptake by these hormones but has little effect on net uptake. Isoproterenol, a beta-adrenergic agonist, stimulates magnesium uptake only minimally. The pattern of uptake stimulated by methoxamine, an alpha-adrenergic agonist, or ACTH-(11-24) is quite similar to that produced by native ACTH in the presence of propranolol. The receptor through which ACTH mediates stimulation of the bulk of magnesium appears to be analogous to the alpha-adrenergic receptor through which norepinephrine stimulates this same process."}
{"id": "PMID:191616", "title": "Isolation and characterization of lymphocyte associated foamy virus from a red uakari monkey (Cacajao rubicundus).", "content": "A syncytium-forming virus was isolated from the lymphocytes of a uakari monkey 70 days after establishing a lymphocyte/owl monkey kidney coculture in the wild. The morphology and morphogenesis of the virus, plus its physicochemical characteristics indicate that the agent is a foamy virus. An unusal cell alteration found in cultures infected with this foamy was the formation of eosinophilic intracytoplasmic inclusion in association with the syncytia. The agent was found to be antigenically distinct to other known simian foamy viruses.", "contents": "Isolation and characterization of lymphocyte associated foamy virus from a red uakari monkey (Cacajao rubicundus). A syncytium-forming virus was isolated from the lymphocytes of a uakari monkey 70 days after establishing a lymphocyte/owl monkey kidney coculture in the wild. The morphology and morphogenesis of the virus, plus its physicochemical characteristics indicate that the agent is a foamy virus. An unusal cell alteration found in cultures infected with this foamy was the formation of eosinophilic intracytoplasmic inclusion in association with the syncytia. The agent was found to be antigenically distinct to other known simian foamy viruses."}
{"id": "PMID:191621", "title": "Human cells transformed in vitro by human cytomegalovirus: tumorigenicity in athymic nude mice.", "content": "Athymic nude mice were inoculated with human embryo lung cells transformed in vitro by human cytomegalovirus (CMV). Of the inoculated animals, 62% developed tumors after an average latent period of 19 days. The tumors were composed of small, polygonal cells with large nulei and scanty cytoplasm embedded in an abundant collagenous matrix. The cells were poorly differentiated but may have been of epithelial origin. Adjacent structures were rarely invaded. CMV-related intracellular and membrane antigens were detected by indirect and anticomplement immunofluorescence techniques in cells cultured in vitro from the tumors.", "contents": "Human cells transformed in vitro by human cytomegalovirus: tumorigenicity in athymic nude mice. Athymic nude mice were inoculated with human embryo lung cells transformed in vitro by human cytomegalovirus (CMV). Of the inoculated animals, 62% developed tumors after an average latent period of 19 days. The tumors were composed of small, polygonal cells with large nulei and scanty cytoplasm embedded in an abundant collagenous matrix. The cells were poorly differentiated but may have been of epithelial origin. Adjacent structures were rarely invaded. CMV-related intracellular and membrane antigens were detected by indirect and anticomplement immunofluorescence techniques in cells cultured in vitro from the tumors."}
{"id": "PMID:191622", "title": "Contact transmission of avian leukosis virus.", "content": "Intravenous inoculation of four age groups of White Leghorn chicks with ALV-F42, a group A field strain of avian leukosis virus (ALV), indicated that persistent tolerant infection could be induced as late as 2 weeks post hatch, though most birds responded with neutralizing antibody. Contact infection by environmental exposure to ALV was 100% effective in newly hatched and 28-day-old chicks. All contact-infected birds responded immunologically after transient viremia. A follow-up of immune birds from these six groups demonstrated that active multiplication of ALV continued despite neutralizing antibody. Infectious virus was shed by oral and cloacal routes, as well as through vertical transmission by hens to their embryos. Up to 10(8) infectious units of virus/g of feces was shed by 12-day-old viremic birds, and to a lesser extent virus was also shed in saliva as measured by oral washing. The cycle of contact transmission was also evaluated by the assessment of the efficacy of four portals of entry, where exposed skin was most effective in permitting infection, followed by oral, nasal, and conjunctival routes.", "contents": "Contact transmission of avian leukosis virus. Intravenous inoculation of four age groups of White Leghorn chicks with ALV-F42, a group A field strain of avian leukosis virus (ALV), indicated that persistent tolerant infection could be induced as late as 2 weeks post hatch, though most birds responded with neutralizing antibody. Contact infection by environmental exposure to ALV was 100% effective in newly hatched and 28-day-old chicks. All contact-infected birds responded immunologically after transient viremia. A follow-up of immune birds from these six groups demonstrated that active multiplication of ALV continued despite neutralizing antibody. Infectious virus was shed by oral and cloacal routes, as well as through vertical transmission by hens to their embryos. Up to 10(8) infectious units of virus/g of feces was shed by 12-day-old viremic birds, and to a lesser extent virus was also shed in saliva as measured by oral washing. The cycle of contact transmission was also evaluated by the assessment of the efficacy of four portals of entry, where exposed skin was most effective in permitting infection, followed by oral, nasal, and conjunctival routes."}
{"id": "PMID:191623", "title": "Surface antigens on transplantable tumor cell lines producing mouse type C viruses.", "content": "A variety of transplantable mouse tumor lines were shown to contain murine type C viruses and virus-associated antigens. The type of virus isolated and antigens detected could not invariably be correlated with the original method of tumor induction, but testing of the majority of tumor lines for infectious virus at various levels of in vivo or in vitro passage yielded isolates that were consistent in tissue culture host range for each tumor. In contrast, during the course of in vivo transplantation, some of the lines underwent considerable change in the pattern of virus-associated cell-surface antigens. When the transplanted tumor lines were placed into culture, all showed some alteration in the detectable surface antigens. Upon retransplantation and passage of the cultured cells in mice, the surface antigens gradually returned to the original in vivo patterns and occasionally acquired additional type C virus-associated antigens not detected in the original tumor line. To test for association of antigens with infectious virus, appropriate tissue culture cell lines were infected with the viruses isolated from the tumors. In these infected indicator cells, some new virus-associated cell-surface and virion evelope antigens were detected, but the complete array of antigens found in the original tumor lines was not acquired. These findings indicated the presence of several different type C viruses in long transplanted cell lines and demonstrated that environmental and host cell factors may have major influences on expression of virus-associated antigens.", "contents": "Surface antigens on transplantable tumor cell lines producing mouse type C viruses. A variety of transplantable mouse tumor lines were shown to contain murine type C viruses and virus-associated antigens. The type of virus isolated and antigens detected could not invariably be correlated with the original method of tumor induction, but testing of the majority of tumor lines for infectious virus at various levels of in vivo or in vitro passage yielded isolates that were consistent in tissue culture host range for each tumor. In contrast, during the course of in vivo transplantation, some of the lines underwent considerable change in the pattern of virus-associated cell-surface antigens. When the transplanted tumor lines were placed into culture, all showed some alteration in the detectable surface antigens. Upon retransplantation and passage of the cultured cells in mice, the surface antigens gradually returned to the original in vivo patterns and occasionally acquired additional type C virus-associated antigens not detected in the original tumor line. To test for association of antigens with infectious virus, appropriate tissue culture cell lines were infected with the viruses isolated from the tumors. In these infected indicator cells, some new virus-associated cell-surface and virion evelope antigens were detected, but the complete array of antigens found in the original tumor lines was not acquired. These findings indicated the presence of several different type C viruses in long transplanted cell lines and demonstrated that environmental and host cell factors may have major influences on expression of virus-associated antigens."}
{"id": "PMID:191624", "title": "Specific simian virus 40 (SV40)-induced immunity against transplantable SV40 tumor in Syrian hamsters: abrogation by BCG vaccination.", "content": "Syrian hamsters were immunized with simian virus 40 (SV40) and/or BCG (in different time and sequence combinations) and were subsequently challenged with SV40-induced transplantable tumor cells. Immunization of hamsters with some but not all BCG preparations alone induced high levels of resistance to SV40 transplantable tumor cells. The immunization with SV40 of hamsters preliminarily inoculated with BCG induced antitumor immunity, the level of which was equal to resistance induced by immunization of normal animals with SV40. No cumulative effects of BCG and SV40 immunizations were noticed in any of our experiments even when BCG prepartions alone induced considerable increase of antitumor resistance. Inoculation of animals with the mixture of SV40 and BCG was generally less effective than that with SV40 alone. Inoculation of BCG preparations into hamsters preimmunized with SV40 resulted in the complete or partial abrogation of the resistance induced by SV40. All preparations of BCG, independent from their antitumor activity per se, decreased the resistance induced by SV40. The effect of this BCG-induced abrogation of resistance was observed in animals immunized with SV40 7-427 days before inoculation of BCG. The effect was not short-term, as it was still observed 3 months after BCG inoculation.", "contents": "Specific simian virus 40 (SV40)-induced immunity against transplantable SV40 tumor in Syrian hamsters: abrogation by BCG vaccination. Syrian hamsters were immunized with simian virus 40 (SV40) and/or BCG (in different time and sequence combinations) and were subsequently challenged with SV40-induced transplantable tumor cells. Immunization of hamsters with some but not all BCG preparations alone induced high levels of resistance to SV40 transplantable tumor cells. The immunization with SV40 of hamsters preliminarily inoculated with BCG induced antitumor immunity, the level of which was equal to resistance induced by immunization of normal animals with SV40. No cumulative effects of BCG and SV40 immunizations were noticed in any of our experiments even when BCG prepartions alone induced considerable increase of antitumor resistance. Inoculation of animals with the mixture of SV40 and BCG was generally less effective than that with SV40 alone. Inoculation of BCG preparations into hamsters preimmunized with SV40 resulted in the complete or partial abrogation of the resistance induced by SV40. All preparations of BCG, independent from their antitumor activity per se, decreased the resistance induced by SV40. The effect of this BCG-induced abrogation of resistance was observed in animals immunized with SV40 7-427 days before inoculation of BCG. The effect was not short-term, as it was still observed 3 months after BCG inoculation."}
{"id": "PMID:191625", "title": "Carcinogenic activity of petasitenine, a new pyrrolizidine alkaloid isolated from Petasites japonicus Maxim.", "content": "The carcinogenic activity of petasitenine, a new pyrrolizidine alkaloid isolated from young flower stalk of Petasites japonicus, was studied in ACI rats. All rats that had received a 0.05% solution of petasitenine in drinking water died or were killed in moribund condition 72 days after the start of experiment. They showed necrosis, hemorrhage, and remarkable proliferation of the bile ducts in the liver. In another group that had received a 0.01% solution, 8 of 10 animals surviving beyond 160 days developed tumors in the liver, i.e., hemangioendothelial sarcomas in 5 rats and liver cell adenomas in 5 rats, 2 of which simultaneously developed hemangioendothelial sarcomas. No tumors were observed in the livers of the control animals.", "contents": "Carcinogenic activity of petasitenine, a new pyrrolizidine alkaloid isolated from Petasites japonicus Maxim. The carcinogenic activity of petasitenine, a new pyrrolizidine alkaloid isolated from young flower stalk of Petasites japonicus, was studied in ACI rats. All rats that had received a 0.05% solution of petasitenine in drinking water died or were killed in moribund condition 72 days after the start of experiment. They showed necrosis, hemorrhage, and remarkable proliferation of the bile ducts in the liver. In another group that had received a 0.01% solution, 8 of 10 animals surviving beyond 160 days developed tumors in the liver, i.e., hemangioendothelial sarcomas in 5 rats and liver cell adenomas in 5 rats, 2 of which simultaneously developed hemangioendothelial sarcomas. No tumors were observed in the livers of the control animals."}
{"id": "PMID:191626", "title": "Promotion of incidence of adenovirus type 12 transplantable tumors by carrageenan, a specific antimacrophage agent.", "content": "Carrageenan, a sulfated polygalactose with known macrophage-toxic properties, was used to ascertain the role of macrophages in resistance to adenovirus type 12 transplantable tumors. A single ip injection of 5 or 10 mg carrageenan led to increased incidence and more rapid growth of tumors in C3H mice. Carrageenan was most effective if given 1 day before tumor inoculation; the effectiveness decreased with increasing intervals before or after tumor cell injection. The macrophage stabilizer poly-2-vinylpyridine N-oxide injected sc (150 mg/kg) 1 day before carrageenan was given reduced the incidence of tumors. These data lend further support to the importance of macrophages in tumor immunity.", "contents": "Promotion of incidence of adenovirus type 12 transplantable tumors by carrageenan, a specific antimacrophage agent. Carrageenan, a sulfated polygalactose with known macrophage-toxic properties, was used to ascertain the role of macrophages in resistance to adenovirus type 12 transplantable tumors. A single ip injection of 5 or 10 mg carrageenan led to increased incidence and more rapid growth of tumors in C3H mice. Carrageenan was most effective if given 1 day before tumor inoculation; the effectiveness decreased with increasing intervals before or after tumor cell injection. The macrophage stabilizer poly-2-vinylpyridine N-oxide injected sc (150 mg/kg) 1 day before carrageenan was given reduced the incidence of tumors. These data lend further support to the importance of macrophages in tumor immunity."}
{"id": "PMID:191627", "title": "Autoradiographic localization of prolactin receptors in 7,12-dimethylbnez[a]anthracene-induced rat mammary carcinoma.", "content": "Prolactin receptors were localized by autoradiography in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors from rats by incubation of tumor slices with [125I]ovine prolactin. Specific prolactin binding was confined to tumor cells, and nonspecific binding was present in alveolar spaces and connective tissue. In some tumors, all cells contained receptors; in others, up to one-half the cells remained unlabeled. These results suggested that variation in receptor content in DMBA-induced mammary tumors may be caused by two distinct populations of cells--one which contains receptors and another which possesses very few receptor sites or none at all.", "contents": "Autoradiographic localization of prolactin receptors in 7,12-dimethylbnez[a]anthracene-induced rat mammary carcinoma. Prolactin receptors were localized by autoradiography in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors from rats by incubation of tumor slices with [125I]ovine prolactin. Specific prolactin binding was confined to tumor cells, and nonspecific binding was present in alveolar spaces and connective tissue. In some tumors, all cells contained receptors; in others, up to one-half the cells remained unlabeled. These results suggested that variation in receptor content in DMBA-induced mammary tumors may be caused by two distinct populations of cells--one which contains receptors and another which possesses very few receptor sites or none at all."}
{"id": "PMID:191628", "title": "Human bladder carcinoma: characterization of two new tumor cell lines and search for tumor viruses.", "content": "Two newly established human bladder carcinoma cell lines, designated HT-1197 and HT-1376, were characterized. Cells of both cultures exhibited fine structural microvilli and tonofibrils indicative of their epithelial origin. In addition, desmosomes were also present in HT-1197. Marker chromosomes present in HT-1197 and HT-1376 distinguished these from each other and from other known human tumor cell lines. Both cultures grew in soft agar, induced fibrinolytic activity, and were tumorigenic in mice and hamsters. No type C or other virus expression was detected in these cell lines nor in other human urothelial tumors tested.", "contents": "Human bladder carcinoma: characterization of two new tumor cell lines and search for tumor viruses. Two newly established human bladder carcinoma cell lines, designated HT-1197 and HT-1376, were characterized. Cells of both cultures exhibited fine structural microvilli and tonofibrils indicative of their epithelial origin. In addition, desmosomes were also present in HT-1197. Marker chromosomes present in HT-1197 and HT-1376 distinguished these from each other and from other known human tumor cell lines. Both cultures grew in soft agar, induced fibrinolytic activity, and were tumorigenic in mice and hamsters. No type C or other virus expression was detected in these cell lines nor in other human urothelial tumors tested."}
{"id": "PMID:191629", "title": "Collateral sensitivity between methylene dimethane sulfonate and halogenated methotrexate derivatives in the Yoshida sarcoma in vivo and in vitro.", "content": "A Yoshida lymphosarcoma line (YMDR8) resistant to methylene dimethane sulfonate (MDMS) showed collateral sensitivity against three halogenated methotrexates: 3'-bromomethotrexate (NSC-98580), 3'-bromo-5'-chloromethotrexate (NSC-98579), and 3',5'-dichloromethotrexate (NSC-29630); however, it was cross-resistant to methotrexate itself. Two other independently derived MDMS-resistant cell lines, YMDR7 and YMDR9, also demonstrated collateral sensitivity against 3'-bromomethotrexate, but with the latter, the origin of the \"induced\" sensitivity probably was not due to interference with antigenic or oncogenic properties of the cell line. When these agents were used in vivo (in Wistar rats) and in vitro, subpopulation changes within the tumor lines could be observed. The possible importance of this parameter in the development of such sensitivity is discussed.", "contents": "Collateral sensitivity between methylene dimethane sulfonate and halogenated methotrexate derivatives in the Yoshida sarcoma in vivo and in vitro. A Yoshida lymphosarcoma line (YMDR8) resistant to methylene dimethane sulfonate (MDMS) showed collateral sensitivity against three halogenated methotrexates: 3'-bromomethotrexate (NSC-98580), 3'-bromo-5'-chloromethotrexate (NSC-98579), and 3',5'-dichloromethotrexate (NSC-29630); however, it was cross-resistant to methotrexate itself. Two other independently derived MDMS-resistant cell lines, YMDR7 and YMDR9, also demonstrated collateral sensitivity against 3'-bromomethotrexate, but with the latter, the origin of the \"induced\" sensitivity probably was not due to interference with antigenic or oncogenic properties of the cell line. When these agents were used in vivo (in Wistar rats) and in vitro, subpopulation changes within the tumor lines could be observed. The possible importance of this parameter in the development of such sensitivity is discussed."}
{"id": "PMID:191630", "title": "Natural antibody in mammary tumor virus-infected mice that reacts with intracytoplasmic A particles of mouse mammary tumors.", "content": "By an indirect immunofluorescence technique with prolonged serum incubation on murine mammary tumor (MT) slices, 179 of 424 mice examined were found to possess natural serum antibody (antibodies) that reacted with intracytoplasmic A particles (iAp) of MT cells. The immunologic specificity of this antibody was supported by absorption and blocking experiments. Furthermore, a strong similarity was seen between the mouse antibody reaction on various MT and the fluorescence pattern of rabbit anti-iAp antiserum on these tumors. In female mice, incidence and geometric mean titers of the antibody in part were correlated to the spontaneous MT frequency of the mouse strains examined. Some mice of the strains XVII/Bin and CBA/BinfXVII/Bin, hitherto regarded as \"free\" of the mouse mammary tumor virus (MuMTV), also contained anti-iAp antibody in their sera. In contrast to MuMTV)-producing CBA/Bin micethese animals did not possess detectable spontaneous antibody reacting with MuMTV-B particles. Therefore, hypothetically, the antibody response in these mice might be induced by incomplete MuMTV expression. In the strain CBA/Bin, females 4 months old and older possessed the antibody in significantly higher geometric mean titers when compared to 4-week-old female mice. The history of lactation seemed to have no influence on the titer of antibody. In the comparatively high MT strains CBA/Bin and C3H/Bin, adult (4-month-old) females had the antibody in significantly higher levels when compared to age-matched males.", "contents": "Natural antibody in mammary tumor virus-infected mice that reacts with intracytoplasmic A particles of mouse mammary tumors. By an indirect immunofluorescence technique with prolonged serum incubation on murine mammary tumor (MT) slices, 179 of 424 mice examined were found to possess natural serum antibody (antibodies) that reacted with intracytoplasmic A particles (iAp) of MT cells. The immunologic specificity of this antibody was supported by absorption and blocking experiments. Furthermore, a strong similarity was seen between the mouse antibody reaction on various MT and the fluorescence pattern of rabbit anti-iAp antiserum on these tumors. In female mice, incidence and geometric mean titers of the antibody in part were correlated to the spontaneous MT frequency of the mouse strains examined. Some mice of the strains XVII/Bin and CBA/BinfXVII/Bin, hitherto regarded as \"free\" of the mouse mammary tumor virus (MuMTV), also contained anti-iAp antibody in their sera. In contrast to MuMTV)-producing CBA/Bin micethese animals did not possess detectable spontaneous antibody reacting with MuMTV-B particles. Therefore, hypothetically, the antibody response in these mice might be induced by incomplete MuMTV expression. In the strain CBA/Bin, females 4 months old and older possessed the antibody in significantly higher geometric mean titers when compared to 4-week-old female mice. The history of lactation seemed to have no influence on the titer of antibody. In the comparatively high MT strains CBA/Bin and C3H/Bin, adult (4-month-old) females had the antibody in significantly higher levels when compared to age-matched males."}
{"id": "PMID:191631", "title": "Spontaneous lymphosarcoma arising in a nude mouse: characterization in vivo and in vitro.", "content": "A lymphosarcoma spontaneously arising in a nude mouse and a continuous cell line (NML-1) derived from it are described and compared. The primary tumor and a transplantable tumor line from it were composed of lymphoid cells, with no C-type viral particles seen by electron microscopy. The culture line was composed of cells with morphologic and functional properties of macrophages; budding C-type particles were abundant. The cells in the tumors produced in nude mice by injection of the NML-1 cells also resembled macrophages morphologically rather than lymphocytes; however, by electron microscopy, no C-type particles were seen. The findings suggest some type of in vivo suppression of complete expression of the virus.", "contents": "Spontaneous lymphosarcoma arising in a nude mouse: characterization in vivo and in vitro. A lymphosarcoma spontaneously arising in a nude mouse and a continuous cell line (NML-1) derived from it are described and compared. The primary tumor and a transplantable tumor line from it were composed of lymphoid cells, with no C-type viral particles seen by electron microscopy. The culture line was composed of cells with morphologic and functional properties of macrophages; budding C-type particles were abundant. The cells in the tumors produced in nude mice by injection of the NML-1 cells also resembled macrophages morphologically rather than lymphocytes; however, by electron microscopy, no C-type particles were seen. The findings suggest some type of in vivo suppression of complete expression of the virus."}
{"id": "PMID:191632", "title": "Effects of lead and other inhibitors on the activation of K+-dependent p-nitrophenylphosphatase activity by glycine.", "content": "The in vitro and in vivo effects of lead on the activation of K+-dependent p-nitrophenylphosphatase activity by glycine were investigated in plasma membranes of male Wistar rat livers. This activation was markedly inhibited by lead in vitro (0.1-5.0 mM) and in vivo (intraperitoneal injection of lead at 4, 8, or 20 mg per 100 g body weight). On the other hand, the in vitro activation of this K+-dependent activity by glycine was about 77% inhibited by ouabain (10 micronM), but about 100% inhibited by oligomycin (20 micronM).", "contents": "Effects of lead and other inhibitors on the activation of K+-dependent p-nitrophenylphosphatase activity by glycine. The in vitro and in vivo effects of lead on the activation of K+-dependent p-nitrophenylphosphatase activity by glycine were investigated in plasma membranes of male Wistar rat livers. This activation was markedly inhibited by lead in vitro (0.1-5.0 mM) and in vivo (intraperitoneal injection of lead at 4, 8, or 20 mg per 100 g body weight). On the other hand, the in vitro activation of this K+-dependent activity by glycine was about 77% inhibited by ouabain (10 micronM), but about 100% inhibited by oligomycin (20 micronM)."}
{"id": "PMID:191633", "title": "Cell-free translation of RNA synthesized in vitro by a transcribing  nucleoprotein complex prepared from purified vesicular stomatitis virus.", "content": "The RNA species synthesized in vitro by a transcribing nucleoprotein (TNP) complex of vesicular stomatitis virus (VSV) were translated with high efficiency in a fractionated cell-free system derived from reticulocytes. The use of TNP complexes isolated from VSV Indiana, VSV New Jersey, and Chandipura viruses showed that in each case the predominant polypeptides synthesized had electrophoretic mobilities identical to their virion N, NS, and M polypeptides in proportions reflecting those found in infected cells rather than purified virions. A minor polypeptide corresponding to unglycosylated polypeptide G was also observed, but the in vitro synthesis of polypeptide L was not detected. The addition of RNase inhibitor to transcription mixtures markedly increased the rate of RNA synthesis. Furthermore, the messenger activity of the RNA was significantly enhanced. The inclusion of S-adenosyl L-methionine during transcription substantially increased the messenger activity of the product RNA, suggesting a requirement for methylation. Fractionation by oligodeoxythymidylic acid-cellulose chromatography revealed that the RNA required a polyadnylic acid tract for messenger activity.", "contents": "Cell-free translation of RNA synthesized in vitro by a transcribing  nucleoprotein complex prepared from purified vesicular stomatitis virus. The RNA species synthesized in vitro by a transcribing nucleoprotein (TNP) complex of vesicular stomatitis virus (VSV) were translated with high efficiency in a fractionated cell-free system derived from reticulocytes. The use of TNP complexes isolated from VSV Indiana, VSV New Jersey, and Chandipura viruses showed that in each case the predominant polypeptides synthesized had electrophoretic mobilities identical to their virion N, NS, and M polypeptides in proportions reflecting those found in infected cells rather than purified virions. A minor polypeptide corresponding to unglycosylated polypeptide G was also observed, but the in vitro synthesis of polypeptide L was not detected. The addition of RNase inhibitor to transcription mixtures markedly increased the rate of RNA synthesis. Furthermore, the messenger activity of the RNA was significantly enhanced. The inclusion of S-adenosyl L-methionine during transcription substantially increased the messenger activity of the product RNA, suggesting a requirement for methylation. Fractionation by oligodeoxythymidylic acid-cellulose chromatography revealed that the RNA required a polyadnylic acid tract for messenger activity."}
{"id": "PMID:191634", "title": "Distinguishable transformation-defective phenotypes among temperature-sensitive mutants of Rous sarcoma virus.", "content": "Eight transformation-defective, temperature-sensitive (ts) mutants of the Prague strain of Rous sarcoma virus, subgroup A, have been isolated after mutagenesis with 5-bromodeoxyuridine followed by selection on the basis of focus tests. Five of these mutants, ts GI201, GI202, GI203, GI204, and GI205, exhibit properties like most previously reported isolates in that they show a temperature-sensitive response to each of a variety of transformation-specific parameters tested. Interestingly, GI201, in addition to the temperature-sensitive defect, carries a lesion that was observed as a nonconditional loss of expression of plasminogen activator protease. Three mutants, ts GI251, GI252, and GI253 have been disignated partial transformation-defective (PTD) mutants since they behave as ts mutants according to some tests for transformation and as wild type according to others. These three mutants fail to form foci at the nonpermissive temperature (41 degrees C) and art nontumorigenic in 3-week-old chickens (body temperature, 42 degrees C). The agglutinability by concanavalin A of cells infected with these mutants shows a definite  temperature sensitivity, as do the rate of 2-deoxyglucose uptake and the disappearance of the 250, 000-dalton normal cell glycoprotein (large, external, transformation sensitive [LETS]). Although the PTD mutant-infected cells, unlike cells infected with other transformation mutants, exhibit a cell-bound plasminogen activator protease at the nonpermissive temperature, this activator is not detectable as a free protease in the medium, as it is with wild-type, virus-infected cells. The PTD mutants behave like the wild-type parent in their ability to induce transformed growth properties in the infected cells, i.e., growth beyond normal cell saturation density with or without serum-supplemented medium and growth leading to colony formation in soft-agar- or methyl cellulose-containing suspension media.", "contents": "Distinguishable transformation-defective phenotypes among temperature-sensitive mutants of Rous sarcoma virus. Eight transformation-defective, temperature-sensitive (ts) mutants of the Prague strain of Rous sarcoma virus, subgroup A, have been isolated after mutagenesis with 5-bromodeoxyuridine followed by selection on the basis of focus tests. Five of these mutants, ts GI201, GI202, GI203, GI204, and GI205, exhibit properties like most previously reported isolates in that they show a temperature-sensitive response to each of a variety of transformation-specific parameters tested. Interestingly, GI201, in addition to the temperature-sensitive defect, carries a lesion that was observed as a nonconditional loss of expression of plasminogen activator protease. Three mutants, ts GI251, GI252, and GI253 have been disignated partial transformation-defective (PTD) mutants since they behave as ts mutants according to some tests for transformation and as wild type according to others. These three mutants fail to form foci at the nonpermissive temperature (41 degrees C) and art nontumorigenic in 3-week-old chickens (body temperature, 42 degrees C). The agglutinability by concanavalin A of cells infected with these mutants shows a definite  temperature sensitivity, as do the rate of 2-deoxyglucose uptake and the disappearance of the 250, 000-dalton normal cell glycoprotein (large, external, transformation sensitive [LETS]). Although the PTD mutant-infected cells, unlike cells infected with other transformation mutants, exhibit a cell-bound plasminogen activator protease at the nonpermissive temperature, this activator is not detectable as a free protease in the medium, as it is with wild-type, virus-infected cells. The PTD mutants behave like the wild-type parent in their ability to induce transformed growth properties in the infected cells, i.e., growth beyond normal cell saturation density with or without serum-supplemented medium and growth leading to colony formation in soft-agar- or methyl cellulose-containing suspension media."}
{"id": "PMID:191635", "title": "Proteins of bovine leukemia virus. I. Characterization and reactions with natural antibodies.", "content": "The bovine leukemia virus (BLV) was purified from a chronically infected fetal lamb kidney cell line. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of this virus revealed the presence of eight distinguishable viral components with molecular weights ranging from 80,000 to 11,000. The major component is a non-glycosylated protein having a molecular weight of 24,000 (p24). At least three heavier polypeptides were found, one of them representing a glycoprotein (gp 60). In addition, four minor polypeptides with respective molecular weights of 19,000, 16,000, 13,000, and 11,000 were identified. In a complement fixation assay using naturally occurring antibodies of a leukemic cow, four polypeptides, which included gp 60, p35, p24, and p16, were found to be reactive.", "contents": "Proteins of bovine leukemia virus. I. Characterization and reactions with natural antibodies. The bovine leukemia virus (BLV) was purified from a chronically infected fetal lamb kidney cell line. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of this virus revealed the presence of eight distinguishable viral components with molecular weights ranging from 80,000 to 11,000. The major component is a non-glycosylated protein having a molecular weight of 24,000 (p24). At least three heavier polypeptides were found, one of them representing a glycoprotein (gp 60). In addition, four minor polypeptides with respective molecular weights of 19,000, 16,000, 13,000, and 11,000 were identified. In a complement fixation assay using naturally occurring antibodies of a leukemic cow, four polypeptides, which included gp 60, p35, p24, and p16, were found to be reactive."}
{"id": "PMID:191636", "title": "RNA synthesis of vesicular stomatitis virus. VII. Complete separation of the mRNA's of vesicular stomatitis virus by duplex formation.", "content": "Full-length virion RNA and complementary mRNA's of vesicular stomatitis virus can be annealed to each other, digested with RNases, and then separated as five unique duplex RNA molecules on polyacrylamide slab gels. Similar RNA duplexes were detected whether mRNA or virion RNA was the radioactive component and whether the mRNA was synthesized in vitro or in vivo. The sharp banding pattern of these RNA molecules was dependent on treatment with RNase T2, suggesting that removal of poly(A) is necessary. Identification of the coding region contained in each RNA duplex was based on their previous identification as single-stranded mRNA on formamide-containing, polyacrylamide gels. Because the two smallest mRNA'S had not been previously separated, their identification was based on their in vitro transcriptional gene order. In the order of increasing mobilities on the slab gels, the RNA duplexes are identified as the hybrid of the region of the genome RNA hybridized to the complementary mRNA coding for the large protein, the glycoprotein, the nucleocapsid protein, the core-associated NS protein, and the matrix protein (L,G,N,NS, and M). Several lines of evidence support the presence of undegraded complete mRNA, excluding poly(A), in these RNA duplexes. Also, the two smallest mRNA's, separated by duplex formation, were denatured, and their individual oligonucleotide fingerprints were determined. From chemical length determinations, the molecular weights of the mRNA, minus poly(A), are 2.78 X 10(5) and 2.5 X 10(5), respectively, for the mRNA's of the NS and M proteins.", "contents": "RNA synthesis of vesicular stomatitis virus. VII. Complete separation of the mRNA's of vesicular stomatitis virus by duplex formation. Full-length virion RNA and complementary mRNA's of vesicular stomatitis virus can be annealed to each other, digested with RNases, and then separated as five unique duplex RNA molecules on polyacrylamide slab gels. Similar RNA duplexes were detected whether mRNA or virion RNA was the radioactive component and whether the mRNA was synthesized in vitro or in vivo. The sharp banding pattern of these RNA molecules was dependent on treatment with RNase T2, suggesting that removal of poly(A) is necessary. Identification of the coding region contained in each RNA duplex was based on their previous identification as single-stranded mRNA on formamide-containing, polyacrylamide gels. Because the two smallest mRNA'S had not been previously separated, their identification was based on their in vitro transcriptional gene order. In the order of increasing mobilities on the slab gels, the RNA duplexes are identified as the hybrid of the region of the genome RNA hybridized to the complementary mRNA coding for the large protein, the glycoprotein, the nucleocapsid protein, the core-associated NS protein, and the matrix protein (L,G,N,NS, and M). Several lines of evidence support the presence of undegraded complete mRNA, excluding poly(A), in these RNA duplexes. Also, the two smallest mRNA's, separated by duplex formation, were denatured, and their individual oligonucleotide fingerprints were determined. From chemical length determinations, the molecular weights of the mRNA, minus poly(A), are 2.78 X 10(5) and 2.5 X 10(5), respectively, for the mRNA's of the NS and M proteins."}
{"id": "PMID:191637", "title": "Characterization of vesicular stomatitis virus mRNA species synthesized in vitro.", "content": "The smallest size class of mRNA (12S) synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus contains two mRNA species of similar molecular weight that code for the viral M and NS proteins. The resolution of these mRNA species was achieved by converting them to duplexes by annealing with the genome RNA, followed by RNase T2 treatment and separation in a polyacrylamide gel. Using this separation technique, the mRNA's were identified by comparing the relative resistance of their syntheses to UV irradiation of the virus. The molecular weights of these two mRNA species calculated as duplex RNAs were smaller than expected. The possible reasons for this discrepancy are discussed.", "contents": "Characterization of vesicular stomatitis virus mRNA species synthesized in vitro. The smallest size class of mRNA (12S) synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus contains two mRNA species of similar molecular weight that code for the viral M and NS proteins. The resolution of these mRNA species was achieved by converting them to duplexes by annealing with the genome RNA, followed by RNase T2 treatment and separation in a polyacrylamide gel. Using this separation technique, the mRNA's were identified by comparing the relative resistance of their syntheses to UV irradiation of the virus. The molecular weights of these two mRNA species calculated as duplex RNAs were smaller than expected. The possible reasons for this discrepancy are discussed."}
{"id": "PMID:191638", "title": "Immunological reactivity of antisera to sodium dodecyl sulfate-derived polypeptides of polyoma virions.", "content": "A study was undertaken to produce antisera to sodium dodecyl sulfate-derived polyoma virion polypeptides. With the use of this antisera, it was possible to detect, by immunofluorescence, cytoplasmic synthesis of V1, V2, and V3 polypeptides at 18 h postinfection and subsequent transport to the nucleus by 22 h postinfection. Anti-V1, anti-V2, and anti-V3 sera did not react with intact virions in an immunodiffusion assay, nor did they possess hemagglutination inhibition or viral neutralization activity. Antiserum produced against the four host histone polypeptides (V4 through V7) demonstrated immunofluorescence when reacted with polyoma-infected cells but not with uninfected cells. Antihistone serum was also capable of neutralizing viral infectivity, inhibiting hemagglutination and reacting with whole virions in an immunodiffusion assay.", "contents": "Immunological reactivity of antisera to sodium dodecyl sulfate-derived polypeptides of polyoma virions. A study was undertaken to produce antisera to sodium dodecyl sulfate-derived polyoma virion polypeptides. With the use of this antisera, it was possible to detect, by immunofluorescence, cytoplasmic synthesis of V1, V2, and V3 polypeptides at 18 h postinfection and subsequent transport to the nucleus by 22 h postinfection. Anti-V1, anti-V2, and anti-V3 sera did not react with intact virions in an immunodiffusion assay, nor did they possess hemagglutination inhibition or viral neutralization activity. Antiserum produced against the four host histone polypeptides (V4 through V7) demonstrated immunofluorescence when reacted with polyoma-infected cells but not with uninfected cells. Antihistone serum was also capable of neutralizing viral infectivity, inhibiting hemagglutination and reacting with whole virions in an immunodiffusion assay."}
{"id": "PMID:191639", "title": "Localization of two cellular forms of the vesicular stomatitis viral glycoprotein.", "content": "Two cell-associated forms of the glycoprotein (G) of vesicular stomatitis virus, termed G1 and G2, have been resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. G1 has the higher electrophoretic mobility, but both forms migrate more slowly than G protein synthesized in a wheat germ cell-free system (G0), which presumably is the unglycosylated form. G1 is a kinetic precursor of the G2 form, and the apparent cause of the electrophoretic difference between the two species is the presence of N-acetylneuraminic acid on the G2 form. Conversion of G1 to G2 occurs 10 to 20 min prior to the appearance of the G2 form of the protein on the cell surface. This suggests that the G protein may be completely glycosylated several minutes prior to its migration to the cell surface and that glycosylation is not the limiting step in its maturation. No glycoprotein comigrating with G0 can be detected in the infected cells, even after 5-min labeling periods; this suggests that partial clycosylation of G occurs concomitantly with or immediately after its synthesis.", "contents": "Localization of two cellular forms of the vesicular stomatitis viral glycoprotein. Two cell-associated forms of the glycoprotein (G) of vesicular stomatitis virus, termed G1 and G2, have been resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. G1 has the higher electrophoretic mobility, but both forms migrate more slowly than G protein synthesized in a wheat germ cell-free system (G0), which presumably is the unglycosylated form. G1 is a kinetic precursor of the G2 form, and the apparent cause of the electrophoretic difference between the two species is the presence of N-acetylneuraminic acid on the G2 form. Conversion of G1 to G2 occurs 10 to 20 min prior to the appearance of the G2 form of the protein on the cell surface. This suggests that the G protein may be completely glycosylated several minutes prior to its migration to the cell surface and that glycosylation is not the limiting step in its maturation. No glycoprotein comigrating with G0 can be detected in the infected cells, even after 5-min labeling periods; this suggests that partial clycosylation of G occurs concomitantly with or immediately after its synthesis."}
{"id": "PMID:191640", "title": "Separate pathways of maturation of the major structural proteins of vesicular stomatitis virus.", "content": "Cell fractionation and protein electrophoresis were used to study the intracellular sites of synthesis and intermediate structures in the assembly of the virion proteins of vesicular stomatitis virus. Each of the three major virion proteins assembled into virions through a separable pathway. The nucleocapsid (N) protein was first a soluble protein and later incorporated into free, cytoplasmic nucleocapsids. A small amount of N protein was bound to membranes at later times, presumably representing either nucleocapsids in the process of budding or completed virions attached to the cell surface. The matrix (M) protein also appeared to be synthesized as a soluble protein, but was then directly incorporated into membranous structures with the same density as whole virus. Very little M protein was ever found in membranes banding at the density of plasma membranes. The M protein entered extracellular virus very quickly, as though it moved directly from a soluble state into budding virus. In contrast, the glycoprotein (G) was always membrane bound; it appeared to be directly inserted into membranes during its synthesis. Glycosylation of the G protein was completed only in smooth membrane fractions, possibly in the Golgi apparatus. After a minimum time of 15 min following its synthesis, G protein was incorporated into the surface plasma membrane, from which it was slowly shed into virions. These multiple processing steps probably account for its delayed appearance in virus. From this work it appears that the three major structural proteins come into the surface budding structure through independent pathways and together they coalesce at the plasma membrane to form the mature virion.", "contents": "Separate pathways of maturation of the major structural proteins of vesicular stomatitis virus. Cell fractionation and protein electrophoresis were used to study the intracellular sites of synthesis and intermediate structures in the assembly of the virion proteins of vesicular stomatitis virus. Each of the three major virion proteins assembled into virions through a separable pathway. The nucleocapsid (N) protein was first a soluble protein and later incorporated into free, cytoplasmic nucleocapsids. A small amount of N protein was bound to membranes at later times, presumably representing either nucleocapsids in the process of budding or completed virions attached to the cell surface. The matrix (M) protein also appeared to be synthesized as a soluble protein, but was then directly incorporated into membranous structures with the same density as whole virus. Very little M protein was ever found in membranes banding at the density of plasma membranes. The M protein entered extracellular virus very quickly, as though it moved directly from a soluble state into budding virus. In contrast, the glycoprotein (G) was always membrane bound; it appeared to be directly inserted into membranes during its synthesis. Glycosylation of the G protein was completed only in smooth membrane fractions, possibly in the Golgi apparatus. After a minimum time of 15 min following its synthesis, G protein was incorporated into the surface plasma membrane, from which it was slowly shed into virions. These multiple processing steps probably account for its delayed appearance in virus. From this work it appears that the three major structural proteins come into the surface budding structure through independent pathways and together they coalesce at the plasma membrane to form the mature virion."}
{"id": "PMID:191641", "title": "Analysis of the defects of temperature-sensitive mutants of vesicular stomatitis virus: intracellular degradation of specific viral proteins.", "content": "The metabolism of viral RNA and proteins has been studied in cells infected with temperature-sensitive mutant strains of vesicular stomatitis virus. Certain viral proteins encoded by the mutant strains, usually the putative mutant protein for the assigned complementation group, were shown to be degraded more rapidly at the nonpermissive temperature than were the wild-type proteins. Group III mutants (tsG33, tsM301) encode M proteins which are degraded three- to fourfold faster than the wild-type protein. This defect cannot be fully rescued by coinfection with wild-type virus, and thus the defect appears to be in the M protein itself. Mutants tsM601 (VI) and tsG41(IV) encode N proteins which are degraded much faster than the wild-type protein and also share the property of being defective in replication of viral RNA, suggesting a correlation between these phenotypic properties. Furthermore, the L proteins of tsG11(I) and tsG13(I) are more labile than the wild-type protein at the nonpermissive temperature. The G protein of tsM501(V) did not undergo the change in electrophoretic mobility previously shown to be the result of sialylation, suggesting that it is defective in maturation or glycosylation at the nonpermissive temperature. Three of the mutants previously isolated in this laboratory, tsM502(V), tsM601(VI), and tsM602(VI), were shown to be defective in viral RNA synthesis at the nonpermissive temperature. Mutant tsM601(VI) was defective mainly in viral RNA replication, whereas tsM502(V) appeared to be totally defective for viral RNA transcription and replication at the nonpermissive temperature.", "contents": "Analysis of the defects of temperature-sensitive mutants of vesicular stomatitis virus: intracellular degradation of specific viral proteins. The metabolism of viral RNA and proteins has been studied in cells infected with temperature-sensitive mutant strains of vesicular stomatitis virus. Certain viral proteins encoded by the mutant strains, usually the putative mutant protein for the assigned complementation group, were shown to be degraded more rapidly at the nonpermissive temperature than were the wild-type proteins. Group III mutants (tsG33, tsM301) encode M proteins which are degraded three- to fourfold faster than the wild-type protein. This defect cannot be fully rescued by coinfection with wild-type virus, and thus the defect appears to be in the M protein itself. Mutants tsM601 (VI) and tsG41(IV) encode N proteins which are degraded much faster than the wild-type protein and also share the property of being defective in replication of viral RNA, suggesting a correlation between these phenotypic properties. Furthermore, the L proteins of tsG11(I) and tsG13(I) are more labile than the wild-type protein at the nonpermissive temperature. The G protein of tsM501(V) did not undergo the change in electrophoretic mobility previously shown to be the result of sialylation, suggesting that it is defective in maturation or glycosylation at the nonpermissive temperature. Three of the mutants previously isolated in this laboratory, tsM502(V), tsM601(VI), and tsM602(VI), were shown to be defective in viral RNA synthesis at the nonpermissive temperature. Mutant tsM601(VI) was defective mainly in viral RNA replication, whereas tsM502(V) appeared to be totally defective for viral RNA transcription and replication at the nonpermissive temperature."}
{"id": "PMID:191642", "title": "Maturation of viral proteins in cells infected with temperature-sensitive mutants of vesicular stomatitis virus.", "content": "Maturation of viral proteins in cells infected with mutants of vesicular stomatitis virus was studied by surface iodination and cell fractionation. The movement of G, M, and N proteins to the virion bud appeared to be interdependent. Mutations thought to be in G protein prevented its migration to the cell surface, allowed neither M nor N protein to become membrane bound, and blocked formation of viral particles. Mutant G protein appeared not to leave the endoplasmic reticulum at the nonpermissive temperature, but this defect was partially reversible. In cells infected with mutants that caused N protein to be degraded rapidly or prevented its assembly into nucleocapsids, M protein did not bind to membranes and G protein matured to the cell surface, but never entered structures with the density of virions. Mutations causing M protein to be degraded prevented virion formation, and G protein behaved as in cells infected by mutants in N protein. These results are consistent with a model of virion formation involving coalescence of soluble nucleocapsid and soluble M protein with G protein already in the plasma membrane.", "contents": "Maturation of viral proteins in cells infected with temperature-sensitive mutants of vesicular stomatitis virus. Maturation of viral proteins in cells infected with mutants of vesicular stomatitis virus was studied by surface iodination and cell fractionation. The movement of G, M, and N proteins to the virion bud appeared to be interdependent. Mutations thought to be in G protein prevented its migration to the cell surface, allowed neither M nor N protein to become membrane bound, and blocked formation of viral particles. Mutant G protein appeared not to leave the endoplasmic reticulum at the nonpermissive temperature, but this defect was partially reversible. In cells infected with mutants that caused N protein to be degraded rapidly or prevented its assembly into nucleocapsids, M protein did not bind to membranes and G protein matured to the cell surface, but never entered structures with the density of virions. Mutations causing M protein to be degraded prevented virion formation, and G protein behaved as in cells infected by mutants in N protein. These results are consistent with a model of virion formation involving coalescence of soluble nucleocapsid and soluble M protein with G protein already in the plasma membrane."}
{"id": "PMID:191643", "title": "Chromatin-like structures obtained after alkaline disruption of bovine and human papillomaviruses.", "content": "Four low-molecular-weight polypeptides migrating like H2a, H2b, H3, and H4 calf liver histones were detected by sodium dodecyl sulfate-acrylamide gel electrophoresis of highly purified preparations of bovine papillomavirus (BPV) and human papillomavirus (HPV). Complexes of these polypeptides and viral DNA were isolated by agarose-gel filtration of the alkaline disruption products of both viruses. When observed under the electron microscope, these complexes appeared as circular structures composed of nucleosomes with a diameter of about 8.0 nm interconnected by a naked DNA filament. The maximal frequency of nucleosomes per molecule was 30 for both viruses, corresponding to a condensation ratio of the viral DNA of 2.5.", "contents": "Chromatin-like structures obtained after alkaline disruption of bovine and human papillomaviruses. Four low-molecular-weight polypeptides migrating like H2a, H2b, H3, and H4 calf liver histones were detected by sodium dodecyl sulfate-acrylamide gel electrophoresis of highly purified preparations of bovine papillomavirus (BPV) and human papillomavirus (HPV). Complexes of these polypeptides and viral DNA were isolated by agarose-gel filtration of the alkaline disruption products of both viruses. When observed under the electron microscope, these complexes appeared as circular structures composed of nucleosomes with a diameter of about 8.0 nm interconnected by a naked DNA filament. The maximal frequency of nucleosomes per molecule was 30 for both viruses, corresponding to a condensation ratio of the viral DNA of 2.5."}
{"id": "PMID:191644", "title": "Human papillomavirus DNA: physical mapping of the cleavage sites of Bacillus amyloliquefaciens (BamI) and Haemophilus parainfluenzae (HpaII) endonucleases and evidence for partial heterogeneity.", "content": "The DNA of human papillomavirus (HPV) obtained from a pool of plantar warts is cleaved by bacillus amyloliquefaciens (BamI) and Haemophilus parainfluenzae (HpaII) restriction endonucleases at one and four specific sites, respectively. These sites were localized on the previously established cleavage map of HPV DNA, using the Hind, HindIII, HpaI, and EcoRI endonuclease restriction sites as reference. The four HpaII sites were mapped, clockwise, at 1.4, 41.1, 44.3, and 52.8% of the genome length from the unique BamI cleavage site taken as point zero. The HpaII site mapped at 1.4% of the genome length was absent in 40 to 50% of the molecules, thus showing a genetic heterogeneity of HPV DNA.", "contents": "Human papillomavirus DNA: physical mapping of the cleavage sites of Bacillus amyloliquefaciens (BamI) and Haemophilus parainfluenzae (HpaII) endonucleases and evidence for partial heterogeneity. The DNA of human papillomavirus (HPV) obtained from a pool of plantar warts is cleaved by bacillus amyloliquefaciens (BamI) and Haemophilus parainfluenzae (HpaII) restriction endonucleases at one and four specific sites, respectively. These sites were localized on the previously established cleavage map of HPV DNA, using the Hind, HindIII, HpaI, and EcoRI endonuclease restriction sites as reference. The four HpaII sites were mapped, clockwise, at 1.4, 41.1, 44.3, and 52.8% of the genome length from the unique BamI cleavage site taken as point zero. The HpaII site mapped at 1.4% of the genome length was absent in 40 to 50% of the molecules, thus showing a genetic heterogeneity of HPV DNA."}
{"id": "PMID:191645", "title": "Contact-inhibited revertant cell lines isolated from simian virus 40-transformed cells. VII. Serum detachment-resistant revertant cells.", "content": "Flat revertant cells of simian virus 40-transformed mouse fibroblasts have been isolated on the basis of resistance to a selective detachment procedure. The revertants are generally similar to those isolated by other procedures.", "contents": "Contact-inhibited revertant cell lines isolated from simian virus 40-transformed cells. VII. Serum detachment-resistant revertant cells. Flat revertant cells of simian virus 40-transformed mouse fibroblasts have been isolated on the basis of resistance to a selective detachment procedure. The revertants are generally similar to those isolated by other procedures."}
{"id": "PMID:191646", "title": "Induction of deoxypyrimidine kinase activity in human embryonic lung cells infected with varicella-zoster virus.", "content": "Deoxypyrimidine kinase (deoxythymidine [TdR] kinase and deoxycytidine kinase) activity was induced in human embryonic lung cells after infection with varicella-zoster virus (VZ virus). Increased enzyme activity was also produced by using cell-associated virus as inoculum instead of cell-free virus. Anti-VZ virus serum inhibited both the appearance of cytopathic effect and the induction of enzyme activity. The induced TdR kinase activity was more thermostable than that induced by herpes simplex virus type 1. Also, the TdR kinase activity of VZ virus-infected cells was inhibited by dTTP less than in mock-infected cells and more than in herpes simplex virus type 1-infected cells.", "contents": "Induction of deoxypyrimidine kinase activity in human embryonic lung cells infected with varicella-zoster virus. Deoxypyrimidine kinase (deoxythymidine [TdR] kinase and deoxycytidine kinase) activity was induced in human embryonic lung cells after infection with varicella-zoster virus (VZ virus). Increased enzyme activity was also produced by using cell-associated virus as inoculum instead of cell-free virus. Anti-VZ virus serum inhibited both the appearance of cytopathic effect and the induction of enzyme activity. The induced TdR kinase activity was more thermostable than that induced by herpes simplex virus type 1. Also, the TdR kinase activity of VZ virus-infected cells was inhibited by dTTP less than in mock-infected cells and more than in herpes simplex virus type 1-infected cells."}
{"id": "PMID:191647", "title": "Pseudotypes of vesicular stomatitis virus with the mixed coat of reticuloendotheliosis virus and vesicular stomatitis virus.", "content": "Vesicular stomatitis virus (VSV) forms pseudotypes with envelope components of reticuloendotheliosis virus (REV). The VSV pseudotype possesses the limited host range and antigenic properties of REV. Approximately 70% of the VSV, Indiana serotype, and 45% of VSV, New Jersey serotype, produced from the REV strain T-transformed chicken bone marrow cells contain mixed envelope components of both VSV and REV. VSV pseudotypes with mixed envelope antigens can be neutralized with excess amounts of either anti-VSV antiserum or anti-REV antiserum.", "contents": "Pseudotypes of vesicular stomatitis virus with the mixed coat of reticuloendotheliosis virus and vesicular stomatitis virus. Vesicular stomatitis virus (VSV) forms pseudotypes with envelope components of reticuloendotheliosis virus (REV). The VSV pseudotype possesses the limited host range and antigenic properties of REV. Approximately 70% of the VSV, Indiana serotype, and 45% of VSV, New Jersey serotype, produced from the REV strain T-transformed chicken bone marrow cells contain mixed envelope components of both VSV and REV. VSV pseudotypes with mixed envelope antigens can be neutralized with excess amounts of either anti-VSV antiserum or anti-REV antiserum."}
{"id": "PMID:191648", "title": "Factors affecting composition and thermostability of mengovirus virions.", "content": "The composition of mengovirus virions produced by infected cells varies with the incubation temperature. Virons produced at 37.0 or 39.5 degrees contain four major polypeptides (alpha, beta, gamma, and delta) and one minor polypeptide (beta'). Virons produced at 31.5 degrees C contain two additional polypeptides (D1 and E). The virions of two temperature-sensitive (ts) and thermolabile mutants of mengovirus (ts25 and ts88) contain an increased amount of polypeptide beta', with a corresponding decrease in polypeptide beta when compared with the wild-type mengovirus.", "contents": "Factors affecting composition and thermostability of mengovirus virions. The composition of mengovirus virions produced by infected cells varies with the incubation temperature. Virons produced at 37.0 or 39.5 degrees contain four major polypeptides (alpha, beta, gamma, and delta) and one minor polypeptide (beta'). Virons produced at 31.5 degrees C contain two additional polypeptides (D1 and E). The virions of two temperature-sensitive (ts) and thermolabile mutants of mengovirus (ts25 and ts88) contain an increased amount of polypeptide beta', with a corresponding decrease in polypeptide beta when compared with the wild-type mengovirus."}
{"id": "PMID:191649", "title": "Amount and distribution of virus-specific sequences in giant RNA molecules isolated from polyoma-infected mouse kidney cells.", "content": "A two-step hybridization with polyoma DNA was used to study the composition of giant RNA molecules synthesized in mouse kidney cells late in productive infection by polyoma virus. Giant molecules longer than a complete transcript of the polyoma genome were purified from cells that had been pulse-labeled for 30 min with [3H]uridine and annealed, under mild conditions (50% formamide, 37 degrees C), with polyoma DNA loaded on nitrocellulose filters. Hybridized RNA (6 to 7% of the entire population of 3H-labeled molecules and up to 15% of the molecules containing polyadenylic acid [poly(A)]] was eluted and annealed a second time with polyoma DNA under more stringent conditions. In this second step, 75% of the 3H-labeled RNA formed an RNase-resistant hybrid. Under the same conditions, complementary RNA hybridized with polyoma DNA to a maximal extent of 80%. Since the difference between 75 and 80% is within the experimental error of the hybridization assay, it is inferred that the giant molecules selected by the first hybridization may consist entirely of virus-specific sequences or contain, at the most, a minor fraction of nonviral sequences. To examine the possibility that such nonviral sequences are clustered at the 3'-terminus of these molecules, poly(A)+ giant RNA, which had not been preselected by hybridization with polyoma DNA, was fragmented by a limited alkaline hydrolysis. Fragments linked to the poly(A) segment were separated from the rest of the cleavage products. A one-step hybridization with polyoma DNA revealed that both fractions contain 8 to 10% of virus-specific sequences. These results indicate that the 3'-termini of the poly(A)+ polyoma-specific giant RNA molecules consist of viral rather than nonviral sequences.", "contents": "Amount and distribution of virus-specific sequences in giant RNA molecules isolated from polyoma-infected mouse kidney cells. A two-step hybridization with polyoma DNA was used to study the composition of giant RNA molecules synthesized in mouse kidney cells late in productive infection by polyoma virus. Giant molecules longer than a complete transcript of the polyoma genome were purified from cells that had been pulse-labeled for 30 min with [3H]uridine and annealed, under mild conditions (50% formamide, 37 degrees C), with polyoma DNA loaded on nitrocellulose filters. Hybridized RNA (6 to 7% of the entire population of 3H-labeled molecules and up to 15% of the molecules containing polyadenylic acid [poly(A)]] was eluted and annealed a second time with polyoma DNA under more stringent conditions. In this second step, 75% of the 3H-labeled RNA formed an RNase-resistant hybrid. Under the same conditions, complementary RNA hybridized with polyoma DNA to a maximal extent of 80%. Since the difference between 75 and 80% is within the experimental error of the hybridization assay, it is inferred that the giant molecules selected by the first hybridization may consist entirely of virus-specific sequences or contain, at the most, a minor fraction of nonviral sequences. To examine the possibility that such nonviral sequences are clustered at the 3'-terminus of these molecules, poly(A)+ giant RNA, which had not been preselected by hybridization with polyoma DNA, was fragmented by a limited alkaline hydrolysis. Fragments linked to the poly(A) segment were separated from the rest of the cleavage products. A one-step hybridization with polyoma DNA revealed that both fractions contain 8 to 10% of virus-specific sequences. These results indicate that the 3'-termini of the poly(A)+ polyoma-specific giant RNA molecules consist of viral rather than nonviral sequences."}
{"id": "PMID:191650", "title": "Regulation of Sendai virus transcription: evidence for a single promoter in vivo.", "content": "The synthesis of Sendai virus RNA species was examined after UV irradiation of cells late in infection. Compared with the inactivation of 50S genomic RNA synthesis, the synthesis of the group of mRNA species that sediments at 18S was inactivated at an average rate consistent with a process of sequential transcription from a single promoter. The rates of inactivation of the synthesis of individual mRNA's separated by polyacrylamide gel electrophoresis confirmed this and, with the aid of additional data, suggested that the order of genes in the Sendai virus genome is: 3'-NP-Fo-M-P-HM-L-5'.", "contents": "Regulation of Sendai virus transcription: evidence for a single promoter in vivo. The synthesis of Sendai virus RNA species was examined after UV irradiation of cells late in infection. Compared with the inactivation of 50S genomic RNA synthesis, the synthesis of the group of mRNA species that sediments at 18S was inactivated at an average rate consistent with a process of sequential transcription from a single promoter. The rates of inactivation of the synthesis of individual mRNA's separated by polyacrylamide gel electrophoresis confirmed this and, with the aid of additional data, suggested that the order of genes in the Sendai virus genome is: 3'-NP-Fo-M-P-HM-L-5'."}
{"id": "PMID:191651", "title": "Cell killing by simian virus 40: impairment of membrane formation and function.", "content": "Simian virus 40 infection of the CV-1 line of green monkey kidney cells results in the release of mitochondrial malic dehydrogenase as early as 24 h. Released malic dehydrogenase is detected in the cytoplasm prior to its appearance in the overlay medium. Infected cells lose the ability to consume oxygen between 48 and 56 h, and damage to the elctron transport system is indicated. Nevertheless, cellular ATP levels remain high as late as 72 h. Infection leads to a stimulation of membrane phospholipid synthesis, which reaches a peak at about 32 h. This is followed by a severe decline in new membrane synthesis, which correlates in time with the release of cytoplasmic lactic dehydrogenase into the overlay media. Lactic dehydrogenase release precedes the accumulation of trypan blue-stainable cells by about 6 h. Infection had no effect on the turnover of prelabeled membrane phospholipids. An early simian virus 40 mutant, tsA58, and a late mutant, tsB11, are both less effective than wild-type virus at causing reduced levels of phospholipid synthesis, enzyme release, and the accumulation of trypan blue-stainable cells. Another late mutant, tsB8, is similar to wild-type virus in these respects. At 64 h, there is no detectable cell-associated lactic dehydrogenase and nearly all the cells are trypan blue stainable. Nevertheless, at concentrations of deoxyglucose in the medium below the transport Km, deoxyglucose uptake was similar in infected and control cultures. With higher concentrations of deoxyglucose in the medium, uptake by the infected cultures exceeded that by the control cultures.", "contents": "Cell killing by simian virus 40: impairment of membrane formation and function. Simian virus 40 infection of the CV-1 line of green monkey kidney cells results in the release of mitochondrial malic dehydrogenase as early as 24 h. Released malic dehydrogenase is detected in the cytoplasm prior to its appearance in the overlay medium. Infected cells lose the ability to consume oxygen between 48 and 56 h, and damage to the elctron transport system is indicated. Nevertheless, cellular ATP levels remain high as late as 72 h. Infection leads to a stimulation of membrane phospholipid synthesis, which reaches a peak at about 32 h. This is followed by a severe decline in new membrane synthesis, which correlates in time with the release of cytoplasmic lactic dehydrogenase into the overlay media. Lactic dehydrogenase release precedes the accumulation of trypan blue-stainable cells by about 6 h. Infection had no effect on the turnover of prelabeled membrane phospholipids. An early simian virus 40 mutant, tsA58, and a late mutant, tsB11, are both less effective than wild-type virus at causing reduced levels of phospholipid synthesis, enzyme release, and the accumulation of trypan blue-stainable cells. Another late mutant, tsB8, is similar to wild-type virus in these respects. At 64 h, there is no detectable cell-associated lactic dehydrogenase and nearly all the cells are trypan blue stainable. Nevertheless, at concentrations of deoxyglucose in the medium below the transport Km, deoxyglucose uptake was similar in infected and control cultures. With higher concentrations of deoxyglucose in the medium, uptake by the infected cultures exceeded that by the control cultures."}
{"id": "PMID:191652", "title": "Quantitation of herpes simplex virus type 1 RNA in infected HeLa cells.", "content": "We have quantitatively analyzed the size and amount of herpes simplex virus (HSV)-specific RNA synthesized in HeLa cells using DNA and RNA excess hybridization. At 2 h after infection (early), transcripts from 20% of the total HSV DNA are present on polyribosomes as poly(A+) RNA. At this time, viral poly(A+) RNA comprises 60 to 75% of the newly synthesized poly(a+) mRNA on polyribosomes. By 6 h after infection (late), poly(A+) HSV RNA transcribed from 35 to 40% of the viral DNA is found on polyribosomes. These viral poly(A+) transcripts comprised as much as 90% of newly synthesized poly(A+) mRNA and are measurably larger than viral poly(A+) transcripts isolated early. Some but not all of this size difference is due to the fact that the poly(A) tails on early transcripts are shorter than those found on transcripts made late. Even late after infection, a small but readily measurable amount of cellular poly(A+) RNA is still being made and entering polyribosome complexes. In the nucleus, late after infection, poly(A+) HSV RNA is complementary to 50% of the total HSV DNA. Both early and late after infection, total nuclear viral transcripts are, on the average, larger than viral transcripts found on polyribosomes; however, nuclear HSV poly(A+) RNA is not measureably larger than the corresponding cytoplasmic viral poly(A+) sequences at either time. A major portion (30 to 40%) of the polyribosomal HSV RNA made either early or late after infection is not polyadenylated. This HSV poly (A-) RNA is transcribed from the same sequences as HSV poly(A+) RNA but, when labeled and isolated either early or late after infection, both nuclear and polyribosomal viral poly(A-) RNA molecules sediment faster in sucrose-formaldehyde gradients than their polyadenylated counterparts.", "contents": "Quantitation of herpes simplex virus type 1 RNA in infected HeLa cells. We have quantitatively analyzed the size and amount of herpes simplex virus (HSV)-specific RNA synthesized in HeLa cells using DNA and RNA excess hybridization. At 2 h after infection (early), transcripts from 20% of the total HSV DNA are present on polyribosomes as poly(A+) RNA. At this time, viral poly(A+) RNA comprises 60 to 75% of the newly synthesized poly(a+) mRNA on polyribosomes. By 6 h after infection (late), poly(A+) HSV RNA transcribed from 35 to 40% of the viral DNA is found on polyribosomes. These viral poly(A+) transcripts comprised as much as 90% of newly synthesized poly(A+) mRNA and are measurably larger than viral poly(A+) transcripts isolated early. Some but not all of this size difference is due to the fact that the poly(A) tails on early transcripts are shorter than those found on transcripts made late. Even late after infection, a small but readily measurable amount of cellular poly(A+) RNA is still being made and entering polyribosome complexes. In the nucleus, late after infection, poly(A+) HSV RNA is complementary to 50% of the total HSV DNA. Both early and late after infection, total nuclear viral transcripts are, on the average, larger than viral transcripts found on polyribosomes; however, nuclear HSV poly(A+) RNA is not measureably larger than the corresponding cytoplasmic viral poly(A+) sequences at either time. A major portion (30 to 40%) of the polyribosomal HSV RNA made either early or late after infection is not polyadenylated. This HSV poly (A-) RNA is transcribed from the same sequences as HSV poly(A+) RNA but, when labeled and isolated either early or late after infection, both nuclear and polyribosomal viral poly(A-) RNA molecules sediment faster in sucrose-formaldehyde gradients than their polyadenylated counterparts."}
{"id": "PMID:191653", "title": "Divergence of baboon endogenous type C virogenes in primates: genomic viral RNA in molecular hybridization experiments.", "content": "RNA purified from two related RNA tumor viruses, one isolated from a baboon, Papio anubis, and the second from cultured blood leukocytes of a patient with acute myelogenous leukemia, was labeled with 125I and hybridized to DNA from different primates. RNA from both viruses showed maximum sequence homology with genes in baboons and little homology with genes of humans. The results confirm earlier suggestions that both viruses originated by transcription of baboon virogenes, and that one was transmitted to humans in nature. Hybridization of the viral RNA to cell DNA followed complicated kinetic patterns, indicating the presence of both repeated and infrequent virogene elements. This conclusion was verified in experiments using varied DNA:RNA ratios. It is proposed that virogenes, though composed of genes repeated 10 times or more, consist of some sequences more preferentially conserved than others. The non-uniformity of virogene sequence conservation limits the use of viral probes in studies concerning certain aspects of virogene evolution.", "contents": "Divergence of baboon endogenous type C virogenes in primates: genomic viral RNA in molecular hybridization experiments. RNA purified from two related RNA tumor viruses, one isolated from a baboon, Papio anubis, and the second from cultured blood leukocytes of a patient with acute myelogenous leukemia, was labeled with 125I and hybridized to DNA from different primates. RNA from both viruses showed maximum sequence homology with genes in baboons and little homology with genes of humans. The results confirm earlier suggestions that both viruses originated by transcription of baboon virogenes, and that one was transmitted to humans in nature. Hybridization of the viral RNA to cell DNA followed complicated kinetic patterns, indicating the presence of both repeated and infrequent virogene elements. This conclusion was verified in experiments using varied DNA:RNA ratios. It is proposed that virogenes, though composed of genes repeated 10 times or more, consist of some sequences more preferentially conserved than others. The non-uniformity of virogene sequence conservation limits the use of viral probes in studies concerning certain aspects of virogene evolution."}
{"id": "PMID:191654", "title": "Homogeneity and complexity of avian oncornavirus proviral DNA determined by molecular hybridization.", "content": "The homogeneity of DNA complementary to the 35S RNA subunit of avian myeloblastosis virus (AMV) has been demonstrated by single or multistep hybridization. For multistep hybridizations, 35S AMV RNA was preselected for its ability to hybridize either to unfractionated leukemic DNA or to leukemic DNA enriched for unique or for reiterated sequences. These experiments indicate that the viral genome is complementary to DNA sequences with a low reiteration frequency. Competition experiments confirm the absence of fast-hybridizing sequences in viral DNA. Computer analyses of the data reveal that there are two to four copies of viral DNA in infected cells.", "contents": "Homogeneity and complexity of avian oncornavirus proviral DNA determined by molecular hybridization. The homogeneity of DNA complementary to the 35S RNA subunit of avian myeloblastosis virus (AMV) has been demonstrated by single or multistep hybridization. For multistep hybridizations, 35S AMV RNA was preselected for its ability to hybridize either to unfractionated leukemic DNA or to leukemic DNA enriched for unique or for reiterated sequences. These experiments indicate that the viral genome is complementary to DNA sequences with a low reiteration frequency. Competition experiments confirm the absence of fast-hybridizing sequences in viral DNA. Computer analyses of the data reveal that there are two to four copies of viral DNA in infected cells."}
{"id": "PMID:191655", "title": "Mechanism of restriction of ecotropic and xenotropic murine leukemia viruses and formation of pseudotypes between the two viruses.", "content": "Ecotropic and xenotropic murine leukemia viruses (MuLV's) constitute separate interference groups; within each group there is cross-interference, but between the groups there is no detectable interference. Interference is manifest against pseudotypes in which the vesicular stomatitis virus genome is contained within the coat of one of the murine leukemia viruses. The pseudotypes display the cell specificity of the leukemia viruses: pseudotypes with an ecotropic MuLV coat infect mouse cells but not rabbit or mink cells; pseudotypes with a xenotropic MuLV coat infect rabbit or mink cells well but mouse cells very poorly. Efficient pseudotype formation also occurs between the two MuLV classes, and both the interference patterns and the cell specificity of these pseudotypes are entirely determined by their envelope. Using these pseudotypes, ecotropic MuLV infection could be established in xenogeneic cells, and the resulting progeny could be scored by using a conventional XC cell assay. Also, xenotropic MuLV infection could be established in a mouse cell, showing that no absolute intracellular barrier against xenotropic virus growth exists in murine cells. The major barriers against both xenotropic and ecotropic MuLV therefore are cell surface barriers. Xenogeneic cells probably lack receptors for ecotropic MuLV, but murine cells may either lack receptors for xenotropic MuLV or have receptors that are blocked by endogenous expression of the glycoprotein of endogenous xenotropic MuLV.", "contents": "Mechanism of restriction of ecotropic and xenotropic murine leukemia viruses and formation of pseudotypes between the two viruses. Ecotropic and xenotropic murine leukemia viruses (MuLV's) constitute separate interference groups; within each group there is cross-interference, but between the groups there is no detectable interference. Interference is manifest against pseudotypes in which the vesicular stomatitis virus genome is contained within the coat of one of the murine leukemia viruses. The pseudotypes display the cell specificity of the leukemia viruses: pseudotypes with an ecotropic MuLV coat infect mouse cells but not rabbit or mink cells; pseudotypes with a xenotropic MuLV coat infect rabbit or mink cells well but mouse cells very poorly. Efficient pseudotype formation also occurs between the two MuLV classes, and both the interference patterns and the cell specificity of these pseudotypes are entirely determined by their envelope. Using these pseudotypes, ecotropic MuLV infection could be established in xenogeneic cells, and the resulting progeny could be scored by using a conventional XC cell assay. Also, xenotropic MuLV infection could be established in a mouse cell, showing that no absolute intracellular barrier against xenotropic virus growth exists in murine cells. The major barriers against both xenotropic and ecotropic MuLV therefore are cell surface barriers. Xenogeneic cells probably lack receptors for ecotropic MuLV, but murine cells may either lack receptors for xenotropic MuLV or have receptors that are blocked by endogenous expression of the glycoprotein of endogenous xenotropic MuLV."}
{"id": "PMID:191656", "title": "Natural immunity in mice to the envelope glycoprotein of endogenous ecotropic type C viruses: neutralization of virus infectivity.", "content": "The ability of naturally immune mouse sera to neutralize ecotropic AKR murine leukemia virus (MuLV) was examined by using unfrozen virus preparations harvested for 1 h. In this assay several mouse sera significantly and consistently neutralized MuLV infectivity. The ability of these sera to neutralize was correlated with the presence of antibodies against MuLV detectable in a radioimmune precipitation assay using radioactively labeled intact virions. This neutralization was specific, in that either N- or B-tropic viruses, but not Friend MuLV, were neutralized. In addition, neutralization could be abrogated with purified AKR MuLV gp71 at concentrations that do not interfere with virus infectivity but could not be abrogated with Rauscher MuLV gp71. Neutralizing activity could be removed by absorption with intact AKR MuLV, but not by absorption with Friend MuLV, a BALB/c xenotropic virus, or with NZB xenotropic virus. All the neutralizing activity of (B6C3)F1 mouse sera was associated with the immunoglobulin G fraction.", "contents": "Natural immunity in mice to the envelope glycoprotein of endogenous ecotropic type C viruses: neutralization of virus infectivity. The ability of naturally immune mouse sera to neutralize ecotropic AKR murine leukemia virus (MuLV) was examined by using unfrozen virus preparations harvested for 1 h. In this assay several mouse sera significantly and consistently neutralized MuLV infectivity. The ability of these sera to neutralize was correlated with the presence of antibodies against MuLV detectable in a radioimmune precipitation assay using radioactively labeled intact virions. This neutralization was specific, in that either N- or B-tropic viruses, but not Friend MuLV, were neutralized. In addition, neutralization could be abrogated with purified AKR MuLV gp71 at concentrations that do not interfere with virus infectivity but could not be abrogated with Rauscher MuLV gp71. Neutralizing activity could be removed by absorption with intact AKR MuLV, but not by absorption with Friend MuLV, a BALB/c xenotropic virus, or with NZB xenotropic virus. All the neutralizing activity of (B6C3)F1 mouse sera was associated with the immunoglobulin G fraction."}
{"id": "PMID:191657", "title": "Isolation of the mouse mammary tumor virus sequences not transmitted as germinal provirus in the C3H and RIII mouse strains.", "content": "Radioactive 60-70S RNA from the mouse mammary tumor virus (MMTV) produced by the C3H mouse mammary tumor cell line (Mm5mt) hybridized to a greater extent, and at a lower Cot1/2 value, to the DNA of C3H mammary tumor cells than to the DNA of C3H liver cells. The 125I-labeled MMTV (C3H) 60-40S RNA was annealed to a vast excess of DNA from C3H livers, and single-stranded RNA was eluted from hydroxylapatite and recovered. This \"recycled RNA\" did not hybridize to the DNA of the apparently normal organs tested from normal or from mammary tumor-bearing C3H mice, but hybridized extensively to both the DNA from the C3H mammary tumor cell line and the DNA from spontaneous C3H mammary tumors. This hybridization could be competed out by the addition of unlabeled MMTV 60-70S RNA but was unaffected by the addition of unlabeled 60-70S RNA of C3H type C virus. Similar experiments were conducted with the RIII mouse strain. We therefore report on the isolation of the sequences of the RNA genomes of the MMTVs from C3H and RIII mice that are transmitted by some mechanism other than via the germ line. These studies further define the differences, via molecular hybridization, between the MMTV-S and the MMTV-L in both C3H and RIII mice.", "contents": "Isolation of the mouse mammary tumor virus sequences not transmitted as germinal provirus in the C3H and RIII mouse strains. Radioactive 60-70S RNA from the mouse mammary tumor virus (MMTV) produced by the C3H mouse mammary tumor cell line (Mm5mt) hybridized to a greater extent, and at a lower Cot1/2 value, to the DNA of C3H mammary tumor cells than to the DNA of C3H liver cells. The 125I-labeled MMTV (C3H) 60-40S RNA was annealed to a vast excess of DNA from C3H livers, and single-stranded RNA was eluted from hydroxylapatite and recovered. This \"recycled RNA\" did not hybridize to the DNA of the apparently normal organs tested from normal or from mammary tumor-bearing C3H mice, but hybridized extensively to both the DNA from the C3H mammary tumor cell line and the DNA from spontaneous C3H mammary tumors. This hybridization could be competed out by the addition of unlabeled MMTV 60-70S RNA but was unaffected by the addition of unlabeled 60-70S RNA of C3H type C virus. Similar experiments were conducted with the RIII mouse strain. We therefore report on the isolation of the sequences of the RNA genomes of the MMTVs from C3H and RIII mice that are transmitted by some mechanism other than via the germ line. These studies further define the differences, via molecular hybridization, between the MMTV-S and the MMTV-L in both C3H and RIII mice."}
{"id": "PMID:191658", "title": "Evidence that herpes simplex virus DNA is transcribed by cellular RNA polymerase B.", "content": "In herpes simplex virus type 1 (HSV-1)-infected HEp-2 cells, amanitin added before or at various times after infection always reduced viral multiplication. Also, the three waves of transcription of HSV-1 DNA, which led to the synthesis of alpha, beta-, and gamma-polypeptides, were all sensitive to amanitin in HEp-2 cells, and the amanitin-sensitive RNA polymerase activities of isolated nuclei were equally sensitive to the inhibitor before and during the infection. On the contrary, HSV-1 DNA transcription was totally unaffected by amanitin in AR1/9-5B cells, a mutant subline of CHO cells that possesses an amanitin-resistant RNA polymerase B. Together, these results strongly suggest that HSV-1 DNA utilizes for its transcription a polymerase undistinguishable from host cell RNA polymerase B with respect to its sensitivity to amanitin.", "contents": "Evidence that herpes simplex virus DNA is transcribed by cellular RNA polymerase B. In herpes simplex virus type 1 (HSV-1)-infected HEp-2 cells, amanitin added before or at various times after infection always reduced viral multiplication. Also, the three waves of transcription of HSV-1 DNA, which led to the synthesis of alpha, beta-, and gamma-polypeptides, were all sensitive to amanitin in HEp-2 cells, and the amanitin-sensitive RNA polymerase activities of isolated nuclei were equally sensitive to the inhibitor before and during the infection. On the contrary, HSV-1 DNA transcription was totally unaffected by amanitin in AR1/9-5B cells, a mutant subline of CHO cells that possesses an amanitin-resistant RNA polymerase B. Together, these results strongly suggest that HSV-1 DNA utilizes for its transcription a polymerase undistinguishable from host cell RNA polymerase B with respect to its sensitivity to amanitin."}
{"id": "PMID:191659", "title": "Klippel-Trenaunay syndrome associated with urinary tract hemangiomas.", "content": "Genitourinary hemangiomas in 2 children with Klippel-Trenaunay syndrome are reported. The presence of cutaneous hemangiomas should alert urologists to the possibility of urinary tract hemangiomas inpatients with gross hematuria. Transurethral manipulation of bladder hemangiomas should be avoided because of the danger of excessive hemorrhage, the treatment of choice being partial cystectomy.", "contents": "Klippel-Trenaunay syndrome associated with urinary tract hemangiomas. Genitourinary hemangiomas in 2 children with Klippel-Trenaunay syndrome are reported. The presence of cutaneous hemangiomas should alert urologists to the possibility of urinary tract hemangiomas inpatients with gross hematuria. Transurethral manipulation of bladder hemangiomas should be avoided because of the danger of excessive hemorrhage, the treatment of choice being partial cystectomy."}
{"id": "PMID:191660", "title": "Nephroblastoma with right atrial extension: preoperative diagnosis and management.", "content": "A 14-year-old black boy, with a large nephroblastoma of the right kidney, had preoperative identification of inferior vena cava and right atrial involvement. Renal arteriography revealed linear arterial channels in the anatomic distribution of the inferior vena cava and venography revealed total caval occlusion and a right atrial mass. Radical excision, using a cardiopulmonary bypass, resulted in a 6-month postoperative survival.", "contents": "Nephroblastoma with right atrial extension: preoperative diagnosis and management. A 14-year-old black boy, with a large nephroblastoma of the right kidney, had preoperative identification of inferior vena cava and right atrial involvement. Renal arteriography revealed linear arterial channels in the anatomic distribution of the inferior vena cava and venography revealed total caval occlusion and a right atrial mass. Radical excision, using a cardiopulmonary bypass, resulted in a 6-month postoperative survival."}
{"id": "PMID:191663", "title": "Studies on serum lipoproteins in renal diseases.", "content": "Serum lipoproteins of 25 patients with uncomplicated renal diseases were studied with polyacrylamide gel block electrophoresis. (1) In the nephrotic syndrome (or nephrotic phase of nephritis), marked increases of chylomicrons, pre-beta lipoprotein or beta lipoprotein and decreases of alpha lipoproteins were detected in the most of the patients. Qualitative change was also frequent as in the glomerulonephritis. (2) In the renovascular hypertension, metabolism of serum lipoproteins was involved also. The principal abnormality was in alpha lipoproteins including the lipid-loaded albumin. Marked increases of alpha lipoproteins, to the level equal to or more than beta lipoprotein, was detected in 2 of 3 patients studied in this period. Surgical correction of abnormal physiology had resulted in a return to a normal lipoprotein profile. (3) In the glomerulonephritis confirmed by biopsies, serum lipoprotein abnormalities were detected more frequently than in the reported past studies as analyzed with the method employed in this study. Qualitative as well as quantitative abnormalities were in beta lipoprotein and alpha lipoproteins in the early and middle phase of the disease process. Gross qualitative change occured frequently. Furthermore, lipoprotein abnormalities in renal diseases were reversible; i.e., when the disease had ameliorated or was corrected surgically, the lipoprotein profile returned to the normal or near-normal profile. In conclusion, the results of the present study indicated that serum lipoprotein disorders are involved in the disease process of three major clinical entities of the renal diseases.", "contents": "Studies on serum lipoproteins in renal diseases. Serum lipoproteins of 25 patients with uncomplicated renal diseases were studied with polyacrylamide gel block electrophoresis. (1) In the nephrotic syndrome (or nephrotic phase of nephritis), marked increases of chylomicrons, pre-beta lipoprotein or beta lipoprotein and decreases of alpha lipoproteins were detected in the most of the patients. Qualitative change was also frequent as in the glomerulonephritis. (2) In the renovascular hypertension, metabolism of serum lipoproteins was involved also. The principal abnormality was in alpha lipoproteins including the lipid-loaded albumin. Marked increases of alpha lipoproteins, to the level equal to or more than beta lipoprotein, was detected in 2 of 3 patients studied in this period. Surgical correction of abnormal physiology had resulted in a return to a normal lipoprotein profile. (3) In the glomerulonephritis confirmed by biopsies, serum lipoprotein abnormalities were detected more frequently than in the reported past studies as analyzed with the method employed in this study. Qualitative as well as quantitative abnormalities were in beta lipoprotein and alpha lipoproteins in the early and middle phase of the disease process. Gross qualitative change occured frequently. Furthermore, lipoprotein abnormalities in renal diseases were reversible; i.e., when the disease had ameliorated or was corrected surgically, the lipoprotein profile returned to the normal or near-normal profile. In conclusion, the results of the present study indicated that serum lipoprotein disorders are involved in the disease process of three major clinical entities of the renal diseases."}
{"id": "PMID:191670", "title": "Inhibitory effects of prostaglandin E1 and E2 on cholinergic transmission in isolated canine tracheal muscle.", "content": "The contractile response of the isolated canine tracheal muscle to the transmural nerve stimulation was depressed by atropine and augmented by physostigmine, indicating that the response was predominantly mediated via the parasympathetic nerve. The contractile response to the transmural nerve stimulation was inhibited by prostaglandin E1 (PGE1) and E2 (PGE2) (10(-7) to 10(-5) g/ml) and the inhibitory action of PGE1 was more potent than that of PGE2. On the other hand, the contractile response of the tracheal muscle to exogenously administered ACh was unaffected by 10(-6) g/ml of PGE1 and PGE2. These findings lend support to the hypothesis that the PGE series, in a manner similar to adrenergic transmission, are involved in a negative feed-back control mechanism for the transmitter release in cholinergic transmission.", "contents": "Inhibitory effects of prostaglandin E1 and E2 on cholinergic transmission in isolated canine tracheal muscle. The contractile response of the isolated canine tracheal muscle to the transmural nerve stimulation was depressed by atropine and augmented by physostigmine, indicating that the response was predominantly mediated via the parasympathetic nerve. The contractile response to the transmural nerve stimulation was inhibited by prostaglandin E1 (PGE1) and E2 (PGE2) (10(-7) to 10(-5) g/ml) and the inhibitory action of PGE1 was more potent than that of PGE2. On the other hand, the contractile response of the tracheal muscle to exogenously administered ACh was unaffected by 10(-6) g/ml of PGE1 and PGE2. These findings lend support to the hypothesis that the PGE series, in a manner similar to adrenergic transmission, are involved in a negative feed-back control mechanism for the transmitter release in cholinergic transmission."}
{"id": "PMID:191671", "title": "Influences of aminophylline and reduction in external Na on the antispasmodic action of isoproterenol in the isolated rat rectum.", "content": "Effects of aminophylline and the reduction in external Na on the antispasmodic action of isoproterenol were investigated in relation to the mobilization of Ca in the isolated rat rectum. The antispasmodic action of isoproterenol on the phasic contractions by acetylcholine and K both in Ca-free and in Ca-free and Na-poor media was potentiated by treatment with aminophylline, however the antispasmodic action was attenuated by reducing Na in the Ca-free medium. Dibutyryl cyclic AMP inhibited media and the inhibitory action was also potentiated by treatment with aminophylline, while the inhibitory action of dibutyryl cyclic AMP was attenuated by reducing Na in the Ca-free medium. From these findings, it appears that isoproterenol inhibits the release of Ca from storage sites induced by acetylcholine and K via the increase of intracellular cyclic AMP content and that the external Na may play an important role in the Ca release-inhibiting effect of cyclic AMP.", "contents": "Influences of aminophylline and reduction in external Na on the antispasmodic action of isoproterenol in the isolated rat rectum. Effects of aminophylline and the reduction in external Na on the antispasmodic action of isoproterenol were investigated in relation to the mobilization of Ca in the isolated rat rectum. The antispasmodic action of isoproterenol on the phasic contractions by acetylcholine and K both in Ca-free and in Ca-free and Na-poor media was potentiated by treatment with aminophylline, however the antispasmodic action was attenuated by reducing Na in the Ca-free medium. Dibutyryl cyclic AMP inhibited media and the inhibitory action was also potentiated by treatment with aminophylline, while the inhibitory action of dibutyryl cyclic AMP was attenuated by reducing Na in the Ca-free medium. From these findings, it appears that isoproterenol inhibits the release of Ca from storage sites induced by acetylcholine and K via the increase of intracellular cyclic AMP content and that the external Na may play an important role in the Ca release-inhibiting effect of cyclic AMP."}
{"id": "PMID:191678", "title": "[Effect of heparin on blood lipids under conditions of endo- and exogenous hyperlipemia].", "content": "In 15 patients suffering from ischemic heart disease and in 5 healthy individuals (controls) the dynamics of the blood lipids content (NEFA, triglycerides and atherogenic lipoproteins) was followed up on an empty stomach, during a 18-hour fasting, after carbohydrate and fat loadings, before and after intravenous administration of heparin. Data on a quick and abrupt rise of the NEFA level and a falling triglycerides concentration, and also on a certain decline in the content of atherogenic lipoproteins following administration of heparin were obtained. In atherosclerotic patients the development of hypertriglyceridemia in response to introduction of glucose and a prolonged rise in the level of triglycerides following a fat loading were recorded. Intravenous administration of heparin with carbohydrates and fat loads contributes in atherosclerotic patients to a rapid fall of the blood plasma tryglycerides concentration.", "contents": "[Effect of heparin on blood lipids under conditions of endo- and exogenous hyperlipemia]. In 15 patients suffering from ischemic heart disease and in 5 healthy individuals (controls) the dynamics of the blood lipids content (NEFA, triglycerides and atherogenic lipoproteins) was followed up on an empty stomach, during a 18-hour fasting, after carbohydrate and fat loadings, before and after intravenous administration of heparin. Data on a quick and abrupt rise of the NEFA level and a falling triglycerides concentration, and also on a certain decline in the content of atherogenic lipoproteins following administration of heparin were obtained. In atherosclerotic patients the development of hypertriglyceridemia in response to introduction of glucose and a prolonged rise in the level of triglycerides following a fat loading were recorded. Intravenous administration of heparin with carbohydrates and fat loads contributes in atherosclerotic patients to a rapid fall of the blood plasma tryglycerides concentration."}
{"id": "PMID:191679", "title": "[Characteristics of energy metabolism in the myocardium under artificial hypothermia].", "content": "The effect of cooling and subsequent rewarming on the tissue respiration of canine hearts was studied during polycomponent ether-oxygen anaesthesia. The tests included the determinations of the activity of the dehydrogenases of the cytrate cycle, the content and activity of chromoproteids, the respiration rate of the mitochondrias on succinate, glutamate and ketoglutarate, the content of glycogen, the activity of the phosphorylases, hexokinase, lactate dehydrogenase, the content of lactate, pyruvate, adenyl nucleotides and creatine phosphate. Significant changes were noted in the content and activity of the above substances, acceleration of mitochondrial respiration, reduced energy regulation of respiration, and decreased amount of the adenyl components. It is suggested that under artificial hypothermia the processes of chromoproteids biosynthesis are enhanced, which results in an increased power of terminal respiration, and conformational rearaangements of the enzymes connected with the membranes occur.", "contents": "[Characteristics of energy metabolism in the myocardium under artificial hypothermia]. The effect of cooling and subsequent rewarming on the tissue respiration of canine hearts was studied during polycomponent ether-oxygen anaesthesia. The tests included the determinations of the activity of the dehydrogenases of the cytrate cycle, the content and activity of chromoproteids, the respiration rate of the mitochondrias on succinate, glutamate and ketoglutarate, the content of glycogen, the activity of the phosphorylases, hexokinase, lactate dehydrogenase, the content of lactate, pyruvate, adenyl nucleotides and creatine phosphate. Significant changes were noted in the content and activity of the above substances, acceleration of mitochondrial respiration, reduced energy regulation of respiration, and decreased amount of the adenyl components. It is suggested that under artificial hypothermia the processes of chromoproteids biosynthesis are enhanced, which results in an increased power of terminal respiration, and conformational rearaangements of the enzymes connected with the membranes occur."}
{"id": "PMID:191680", "title": "Effect of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on isotonic fluid reabsorption: polarity of proximal tubular cells.", "content": "Isotomic fluid reabsorption (JV) of rat renal proximal tubules was examined by the shrinking droplet method in combination with simulatneous perfusion of blood capillaries. Sensitivity of JV measurement was improved by using each punctured tubule for control measurements: 1) Parathyroid hormoen (PTH) on the contraluminal cell side reduced JV in a dose-response behavior. The maximal inhibition was achieved at a PTH concentration of 10(-5) M, the half maximal inhibition at a concentration of 3 X 10(-9) M. PTH on the luminal cell side had a small inhibitory effect. 2) Cyclic AMP inhibited JV preferentially when applied to the luminal cell side. On the luminal cell side, both cyclic AMP and dibutyryl cyclic AMP inhibited JV in a similar dose-dependent behavior. Concentrations of both nucleotides as low as 10(-10) M had a definite inhibitory effect. Tested at a high concentration, N6-butyryl cyclic AMP was almost as effective as cyclic AMP. Deoxy cyclic AMP, 5' AMP, cyclic guanosine monophosphate (cyclic GMP), dibutyryl cyclic GMP had no effect. ATP inhibited JV to a very small extent. 3) The reduction of JV after administration of PTH and dibutyryl cyclic AMP was not additive. The similar inhibitory effect of PTH at the contraluminal cell face and of cyclic AMP at the luminal cell face suggests the following sequence of events in the mediation of the action of PTH: 1) activation of adenylate cyclase by PTH in the contraluminal cell membrane, and 2) action of the generated cyclic AMP on the luminal cell membrane. The interaction of cyclic AMP and the luminal cell membrane is initiated at the luminal cell surface.", "contents": "Effect of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on isotonic fluid reabsorption: polarity of proximal tubular cells. Isotomic fluid reabsorption (JV) of rat renal proximal tubules was examined by the shrinking droplet method in combination with simulatneous perfusion of blood capillaries. Sensitivity of JV measurement was improved by using each punctured tubule for control measurements: 1) Parathyroid hormoen (PTH) on the contraluminal cell side reduced JV in a dose-response behavior. The maximal inhibition was achieved at a PTH concentration of 10(-5) M, the half maximal inhibition at a concentration of 3 X 10(-9) M. PTH on the luminal cell side had a small inhibitory effect. 2) Cyclic AMP inhibited JV preferentially when applied to the luminal cell side. On the luminal cell side, both cyclic AMP and dibutyryl cyclic AMP inhibited JV in a similar dose-dependent behavior. Concentrations of both nucleotides as low as 10(-10) M had a definite inhibitory effect. Tested at a high concentration, N6-butyryl cyclic AMP was almost as effective as cyclic AMP. Deoxy cyclic AMP, 5' AMP, cyclic guanosine monophosphate (cyclic GMP), dibutyryl cyclic GMP had no effect. ATP inhibited JV to a very small extent. 3) The reduction of JV after administration of PTH and dibutyryl cyclic AMP was not additive. The similar inhibitory effect of PTH at the contraluminal cell face and of cyclic AMP at the luminal cell face suggests the following sequence of events in the mediation of the action of PTH: 1) activation of adenylate cyclase by PTH in the contraluminal cell membrane, and 2) action of the generated cyclic AMP on the luminal cell membrane. The interaction of cyclic AMP and the luminal cell membrane is initiated at the luminal cell surface."}
{"id": "PMID:191682", "title": "Hyperparathyoidism: influence of glomerular filtration rate on urinary excretion of cyclic AMP.", "content": "Urinary cyclic AMP excretion per 24 h or per g creatinine in primary hyperparathyroidism (1 degrees HPT) has been evaluated by several authors with conflicting results. In 50 patients with 1 degrees HPT, 25 patients with secondary (2 degrees) HPT and 35 healthy control persons we determined urinary cyclic AMP per 24 h or per g creatinine. These parameters did not satisfactorily discriminate patients from controls, especially when glomerular filtration rate (GFR) as determined by creatinine clearance was reduced. Since urinary cyclic AMP is derived from plasma by glomerular filtration and from kidney by tubular production-the amount of tubules is reflected by GFR-the cyclic nucleotide was related to GFR. In controls urinary cyclic AMP correlated better with GFR than with creatinine excretion. Additionally, in 45 of 50 patients with 1 degrees HPT and in all with 2 degrees HPT, urinary cyclic AMP/GFR was raised. In 1 degrees HPT serum levels of parathyroid hormone correlated closer with urinary cyclic AMP/GFR than with urinary cyclic AMP/g creatinine. The ratio cyclic AMP/GFR decreased to normal or subnormal values after removal of adenomatous or hyperplastic glands in 1 degrees HPT and during infusion of calcium in 2 degrees HPT. In 50 patients with renal lithiasis caused by diseases other than 1 degrees HPT (anatomical variations, pyelonephritis, immobilization after tetraplegia) the ratio cyclic AMP/GFR was not raised. Urinary cyclic AMP/GFR, therefore, reflects parathyroid hormone excess more reliably than cyclic AMP/g creatinine.", "contents": "Hyperparathyoidism: influence of glomerular filtration rate on urinary excretion of cyclic AMP. Urinary cyclic AMP excretion per 24 h or per g creatinine in primary hyperparathyroidism (1 degrees HPT) has been evaluated by several authors with conflicting results. In 50 patients with 1 degrees HPT, 25 patients with secondary (2 degrees) HPT and 35 healthy control persons we determined urinary cyclic AMP per 24 h or per g creatinine. These parameters did not satisfactorily discriminate patients from controls, especially when glomerular filtration rate (GFR) as determined by creatinine clearance was reduced. Since urinary cyclic AMP is derived from plasma by glomerular filtration and from kidney by tubular production-the amount of tubules is reflected by GFR-the cyclic nucleotide was related to GFR. In controls urinary cyclic AMP correlated better with GFR than with creatinine excretion. Additionally, in 45 of 50 patients with 1 degrees HPT and in all with 2 degrees HPT, urinary cyclic AMP/GFR was raised. In 1 degrees HPT serum levels of parathyroid hormone correlated closer with urinary cyclic AMP/GFR than with urinary cyclic AMP/g creatinine. The ratio cyclic AMP/GFR decreased to normal or subnormal values after removal of adenomatous or hyperplastic glands in 1 degrees HPT and during infusion of calcium in 2 degrees HPT. In 50 patients with renal lithiasis caused by diseases other than 1 degrees HPT (anatomical variations, pyelonephritis, immobilization after tetraplegia) the ratio cyclic AMP/GFR was not raised. Urinary cyclic AMP/GFR, therefore, reflects parathyroid hormone excess more reliably than cyclic AMP/g creatinine."}
{"id": "PMID:191694", "title": "Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the ultrastructure of parathyroid glands and plasma immunoreactive parathyroid hormone in pregnant cows fed a low calcium diet.", "content": "The long term (70 days) effects of administering ethane-1-hydroxy-1,1-diphosphonate (EHDP) (4 mg. per kg. per day) on parathyroid function was investigated in pregnant cows fed a low calcium diet. Serum calcium and phosphorus were significantly lower at parturition and postpartum in EHDP-treated cows compared to pregnant control cows fed the low calcium diet. Plasma immunoreactive parathyroid hormone levels were similar prepartum, at parturition, and postpartum in cows administered EHDP and control cows. Immediately available calcium reserves were greater preparation in control cows than in cows receiving EHDP as indicated by a more rapid rate of return of serum calcium toward normal levels following ethylenediaminetetraacetic acid (EDTA)-induced hypocalcemia approximately 10 days prepartum. EHDP-treated cows responded to the hypocalcemic challenge with similar changes in plasma immunoreactive parathyroid hormone levels as in control cows; however, urinary hydroxyproline excretion increased at certain intervals only in control cows. Ultrastructurally, chief cells in parathyroid glands of both groups of cows were in an active stage of the secretory cycle with well developed organelles concerned with hormonela synthesis. Chief cells in cows administered EHDP were degranulated and contained fewer secretory granules in response to the hypocalcemia than those in control cows. Chief cells in EHDP-treated cows often had prominent perinuclear accumulations of microfilaments, scattered vacuolated mitochondria, and lysosomal bodies in the cytoplasm. Thyroid C-cells were densely granulated and thyroid calcitonin content was similar in both groups of cows. The principal defect in calcium homeostasis of EHDP-treated cows appeared to be an impairment both in bone calcium mobilization and bone matrix catabolism in response to the secretion of parathyroid hormone. In vitro uptake of 45Ca by duodenal mucosa and urinary excretion of cyclic adenosine monophosphate were similar in both groups of cows. The ability of the parathyroid glands to synthesize and secrete parathyroid hormone in response to hypocalcemia induced either by EDTA or associated with parturition was not impaired by the administration of EHDP.", "contents": "Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the ultrastructure of parathyroid glands and plasma immunoreactive parathyroid hormone in pregnant cows fed a low calcium diet. The long term (70 days) effects of administering ethane-1-hydroxy-1,1-diphosphonate (EHDP) (4 mg. per kg. per day) on parathyroid function was investigated in pregnant cows fed a low calcium diet. Serum calcium and phosphorus were significantly lower at parturition and postpartum in EHDP-treated cows compared to pregnant control cows fed the low calcium diet. Plasma immunoreactive parathyroid hormone levels were similar prepartum, at parturition, and postpartum in cows administered EHDP and control cows. Immediately available calcium reserves were greater preparation in control cows than in cows receiving EHDP as indicated by a more rapid rate of return of serum calcium toward normal levels following ethylenediaminetetraacetic acid (EDTA)-induced hypocalcemia approximately 10 days prepartum. EHDP-treated cows responded to the hypocalcemic challenge with similar changes in plasma immunoreactive parathyroid hormone levels as in control cows; however, urinary hydroxyproline excretion increased at certain intervals only in control cows. Ultrastructurally, chief cells in parathyroid glands of both groups of cows were in an active stage of the secretory cycle with well developed organelles concerned with hormonela synthesis. Chief cells in cows administered EHDP were degranulated and contained fewer secretory granules in response to the hypocalcemia than those in control cows. Chief cells in EHDP-treated cows often had prominent perinuclear accumulations of microfilaments, scattered vacuolated mitochondria, and lysosomal bodies in the cytoplasm. Thyroid C-cells were densely granulated and thyroid calcitonin content was similar in both groups of cows. The principal defect in calcium homeostasis of EHDP-treated cows appeared to be an impairment both in bone calcium mobilization and bone matrix catabolism in response to the secretion of parathyroid hormone. In vitro uptake of 45Ca by duodenal mucosa and urinary excretion of cyclic adenosine monophosphate were similar in both groups of cows. The ability of the parathyroid glands to synthesize and secrete parathyroid hormone in response to hypocalcemia induced either by EDTA or associated with parturition was not impaired by the administration of EHDP."}
{"id": "PMID:191695", "title": "Platelet aggregating material in mouse tumor cells. Removal and regeneration.", "content": "The platelet aggregating principle of two mouse ascites tumors and of their cell-free supernatants released spontaneously has been studied. It was found that the principle disappeared from the cells after trypsin digestion and that part of it was recovered in the cell-free trypsinate. Digested cells regenerated the principle during subsequent incubation by a process requiring protein synthesis. The principle was found to be spontaneously released by intact cells into the medium and sensitive to proteolytic attack. The principle was not present in five varieties of nonneoplastic cells. Since previous work by the authors indicates that the principle is present in numerous other tumor cell lines, its study might reveal it to be an indicator of malignant transformation or malignant progression.", "contents": "Platelet aggregating material in mouse tumor cells. Removal and regeneration. The platelet aggregating principle of two mouse ascites tumors and of their cell-free supernatants released spontaneously has been studied. It was found that the principle disappeared from the cells after trypsin digestion and that part of it was recovered in the cell-free trypsinate. Digested cells regenerated the principle during subsequent incubation by a process requiring protein synthesis. The principle was found to be spontaneously released by intact cells into the medium and sensitive to proteolytic attack. The principle was not present in five varieties of nonneoplastic cells. Since previous work by the authors indicates that the principle is present in numerous other tumor cell lines, its study might reveal it to be an indicator of malignant transformation or malignant progression."}
{"id": "PMID:191696", "title": "Post-kala-azar dermal leishmaniasis simulating leprosy. (A case report).", "content": "The case of a 40 years male suffering from post-kala-azar dermal leishmaniasis simulating nodular lepromatous leprosy is reported. In countries where leprosy is endemic, other diseases are not infrequently taken to be leprosy (Schaller, 1971). Dermal leishmaniasis is a common cause of confusion in countries where the condition is endemic (Browne, 1964). Dharmendra and Chatterji (1940) discussed in detail the question of differential diagnosis between Leprosy and Dermal Leishmaniasis. The present communication is concerned with a patient suffering from post-kala-azar dermal leishmaniasis whose skin lesions simulated nodular lepromatous leprosy.", "contents": "Post-kala-azar dermal leishmaniasis simulating leprosy. (A case report). The case of a 40 years male suffering from post-kala-azar dermal leishmaniasis simulating nodular lepromatous leprosy is reported. In countries where leprosy is endemic, other diseases are not infrequently taken to be leprosy (Schaller, 1971). Dermal leishmaniasis is a common cause of confusion in countries where the condition is endemic (Browne, 1964). Dharmendra and Chatterji (1940) discussed in detail the question of differential diagnosis between Leprosy and Dermal Leishmaniasis. The present communication is concerned with a patient suffering from post-kala-azar dermal leishmaniasis whose skin lesions simulated nodular lepromatous leprosy."}
{"id": "PMID:191699", "title": "The correlation of plasma membrane microvilli and intracellular cyclic AMP content in a rat epitheloid kidney cell line.", "content": "Modulation of the intracellular concentration of cyclic AMP has been associated with a regulatory role in cell division, cell morphology, and physical properties of the plasma membrane. Untransformed rat kidney cells in culture exhibit epitheloid morphology, high intracellular cyclic AMP levels, and contact inhibition of growth. Untransformed rat kidney cells transformed with the Kirsten murine sarcoma virus exhibit a low cyclic AMP content, rapid growth rate, and a loss of contact inhibition. Scanning electron microscopy reveals a distinctive difference in the surface structure of the two cell types during Gl of the cell cycle. The surface of the transformed cell is covered with microvilli while its untransformed counterpart is devoid of microvilli. The presence of microvilli can be controlled as a function of temperature by two temperature-sensitive mutants of the Kirsten sarcoma virus (ts6t6 and ts371 cl 5). In the ts6t6 mutant, growth at 32 degrees C results in a low cyclic AMP content and the presence of microville, while growth at 39 degrees C results in a high cyclic AMP content and a decrease in microvilli. The opposite effect is seen with the ts371 cl 5 mutant. Correlation of cyclic AMP content with the presence of microvilli suggests that this surface phenomenon is a function of cyclic AMP concentration.", "contents": "The correlation of plasma membrane microvilli and intracellular cyclic AMP content in a rat epitheloid kidney cell line. Modulation of the intracellular concentration of cyclic AMP has been associated with a regulatory role in cell division, cell morphology, and physical properties of the plasma membrane. Untransformed rat kidney cells in culture exhibit epitheloid morphology, high intracellular cyclic AMP levels, and contact inhibition of growth. Untransformed rat kidney cells transformed with the Kirsten murine sarcoma virus exhibit a low cyclic AMP content, rapid growth rate, and a loss of contact inhibition. Scanning electron microscopy reveals a distinctive difference in the surface structure of the two cell types during Gl of the cell cycle. The surface of the transformed cell is covered with microvilli while its untransformed counterpart is devoid of microvilli. The presence of microvilli can be controlled as a function of temperature by two temperature-sensitive mutants of the Kirsten sarcoma virus (ts6t6 and ts371 cl 5). In the ts6t6 mutant, growth at 32 degrees C results in a low cyclic AMP content and the presence of microville, while growth at 39 degrees C results in a high cyclic AMP content and a decrease in microvilli. The opposite effect is seen with the ts371 cl 5 mutant. Correlation of cyclic AMP content with the presence of microvilli suggests that this surface phenomenon is a function of cyclic AMP concentration."}
{"id": "PMID:191701", "title": "Quality-of-care assessment. II. Outpatient medical care following hospital dismissal after myocardial infarction.", "content": "This study was undertaken to compare process and outcome methods of quality assessment of medical care in outpatient office practice. Follow-up care after hospitalization for first acute myocardial infarction was used as the model. One hundred fifty-two patients followed up for a minimum of 2 years comprised the study group. An expert committee of cardiologists and internists in community practice established the process criteria for satisfactory care and predicted outcomes of continuing disability and mortality. Using weighted process criteria and a weighted performance index permitted demonstration of a significant association between process items performed at the first posthospitalization visit and 2-year mortality. A significant association could not be demonstrated between later process of care and outcome at 2 years. The outcome assessment study disclosed that predicted disability and mortality rates compared closely with observed outcomes. However, this method for evaluating the quality of outpatient medical care is weakened because little information is available to provide the basis of prediction of satisfactory outcome rates in complicated cases. Although both the process and outcome methods of quality assessment have short comings, the latter method is recommended because satisfactory outcomes is the essential criterion of quality medical care. Moreover, when process items are not specified outcome assessment maintains the flexibility of individual physician practice. Refinement of satisfactory outcome prediction for common illnesses managed in office practice should be the goal for future studies.", "contents": "Quality-of-care assessment. II. Outpatient medical care following hospital dismissal after myocardial infarction. This study was undertaken to compare process and outcome methods of quality assessment of medical care in outpatient office practice. Follow-up care after hospitalization for first acute myocardial infarction was used as the model. One hundred fifty-two patients followed up for a minimum of 2 years comprised the study group. An expert committee of cardiologists and internists in community practice established the process criteria for satisfactory care and predicted outcomes of continuing disability and mortality. Using weighted process criteria and a weighted performance index permitted demonstration of a significant association between process items performed at the first posthospitalization visit and 2-year mortality. A significant association could not be demonstrated between later process of care and outcome at 2 years. The outcome assessment study disclosed that predicted disability and mortality rates compared closely with observed outcomes. However, this method for evaluating the quality of outpatient medical care is weakened because little information is available to provide the basis of prediction of satisfactory outcome rates in complicated cases. Although both the process and outcome methods of quality assessment have short comings, the latter method is recommended because satisfactory outcomes is the essential criterion of quality medical care. Moreover, when process items are not specified outcome assessment maintains the flexibility of individual physician practice. Refinement of satisfactory outcome prediction for common illnesses managed in office practice should be the goal for future studies."}
{"id": "PMID:191703", "title": "Decreased adenosine cyclic 3',5'-monophosphate phosphodiesterase activity in rat straitum following chronic haloperidol treatment.", "content": "The possible involvement of cyclic nucleotide phosphodiesterase (PDE) in the supersensitivity to dopamine-receptor agonists after chronic treatment with neuroleptic drugs has been studied. Rats were given haloperidol in the drinking water for 18 days and finally injected i.p. with 10 mg/kg haloperidol. During and after this treatment the low Km form of the cyclic AMP PDE in a 10,000 g supernatant of the striata was reduced. The loss in enzyme activity was associated with a change in the chromatographic behaviour on DEAE-cellulose. The difference between control- and haloperidol-treated rats was most pronounced in the presence of 1 mM ethylene glycol-bis(aminoethylether)tetraacetic acid (EGTA) and was essentially abolished at 1 mM Ca++. This decrease in cyclic AMP PDE may explain some of the supersensitivity to dopamine-receptor agonists observed following chronic neuroleptic treatment.", "contents": "Decreased adenosine cyclic 3',5'-monophosphate phosphodiesterase activity in rat straitum following chronic haloperidol treatment. The possible involvement of cyclic nucleotide phosphodiesterase (PDE) in the supersensitivity to dopamine-receptor agonists after chronic treatment with neuroleptic drugs has been studied. Rats were given haloperidol in the drinking water for 18 days and finally injected i.p. with 10 mg/kg haloperidol. During and after this treatment the low Km form of the cyclic AMP PDE in a 10,000 g supernatant of the striata was reduced. The loss in enzyme activity was associated with a change in the chromatographic behaviour on DEAE-cellulose. The difference between control- and haloperidol-treated rats was most pronounced in the presence of 1 mM ethylene glycol-bis(aminoethylether)tetraacetic acid (EGTA) and was essentially abolished at 1 mM Ca++. This decrease in cyclic AMP PDE may explain some of the supersensitivity to dopamine-receptor agonists observed following chronic neuroleptic treatment."}
{"id": "PMID:191704", "title": "Combined approach surgery for removal of glomus jugulare tumors.", "content": "The ideal surgical treatment for glomus jugulare tumors is total removal. Efforts have been made periodically to accomplish this since shortly after this tumor was first identified in the early 1940's. This paper describes a method of removal using a combined approach through the neck and temporal bone, preceded by a course of preoperative irradiation therapy. The early results that have been obtained using this procedure in 10 patients are reported.", "contents": "Combined approach surgery for removal of glomus jugulare tumors. The ideal surgical treatment for glomus jugulare tumors is total removal. Efforts have been made periodically to accomplish this since shortly after this tumor was first identified in the early 1940's. This paper describes a method of removal using a combined approach through the neck and temporal bone, preceded by a course of preoperative irradiation therapy. The early results that have been obtained using this procedure in 10 patients are reported."}
{"id": "PMID:191705", "title": "Localization of collagenase in human middle ear cholesteatoma.", "content": "The process of connective tissue breakdown in chronic otitis media is described in the context of recent advances in our understanding of collagen degradation and bone resorption. The significance of the initial step in collagen breakdown, brought about by the action of a specific collagen dissolving enzyme is emphasized in terms of recent studies in other chronic inflammatory diseases characterized by connective tissue breakdown. Bone resorption, a characteristic feature of chronic otitis media, requires the breakdown of collagen, which comprises over 90 percent of bone protein. Evidence in support of collagenase in bone resorption from adjacent tissue (in this case, inflammatory connective tissue) would require identification of the enzyme in cells involved in the inflammatory process adjacent to the resorbing bone. Collagenase was found localized in frozen sections of canal wall skin, middle ear granulation and in cholesteatoma by a specific binding of the enzyme with an antiserum produced against purified human skin collagenase. The antigen antibody complex was labelled with fluorescein. Collagenase appeared in the subepithelial connective tissue of cholesteatoma, granulation tissue from the middle ear and the dermis of canal skin; but was not seen in the keratin layer, epithelium or the epidermal appendages. The enzyme appeared within certain fibroblasts, macrophages and endothelial cells of capillary buds. Collagenase enhanced by chronic inflammation attacks the intact collagen molecule, making it susceptible to further digestion by other proteases that are also products of inflammation. This process brings about resorption of connective tissue and bone.", "contents": "Localization of collagenase in human middle ear cholesteatoma. The process of connective tissue breakdown in chronic otitis media is described in the context of recent advances in our understanding of collagen degradation and bone resorption. The significance of the initial step in collagen breakdown, brought about by the action of a specific collagen dissolving enzyme is emphasized in terms of recent studies in other chronic inflammatory diseases characterized by connective tissue breakdown. Bone resorption, a characteristic feature of chronic otitis media, requires the breakdown of collagen, which comprises over 90 percent of bone protein. Evidence in support of collagenase in bone resorption from adjacent tissue (in this case, inflammatory connective tissue) would require identification of the enzyme in cells involved in the inflammatory process adjacent to the resorbing bone. Collagenase was found localized in frozen sections of canal wall skin, middle ear granulation and in cholesteatoma by a specific binding of the enzyme with an antiserum produced against purified human skin collagenase. The antigen antibody complex was labelled with fluorescein. Collagenase appeared in the subepithelial connective tissue of cholesteatoma, granulation tissue from the middle ear and the dermis of canal skin; but was not seen in the keratin layer, epithelium or the epidermal appendages. The enzyme appeared within certain fibroblasts, macrophages and endothelial cells of capillary buds. Collagenase enhanced by chronic inflammation attacks the intact collagen molecule, making it susceptible to further digestion by other proteases that are also products of inflammation. This process brings about resorption of connective tissue and bone."}
{"id": "PMID:191716", "title": "Activity of phospholipid-synthesizing enzymes in rat liver plasma membranes and the source of biliary lecithin.", "content": "The potential for the synthesis of phosphatidylcholine by the bile canalicular membrane of the liver cell was assessed by measuring the activity of a number of phospholipid synthesizing enzymes in isolated bile canalicular membrane fractions from rat liver. The activity of these various enzymes was compared to that present in noncanalicular liver cell plasma membranes and in microsomes. The CDP-choline:1,2-diacyl-sn-glycerol-cholinephosphotransferase was virtually absent from the bile canalicular membranes but the specific activities of S-adenosyl-L-methionine:phosphatidyl-ethanolamine N-methyltransferase and acyl-CoA:1-acyl-sn-glycero-3-phosphorylcholine acyltransferase were 11-15% of those found in the microsomes. The bile canalicular membranes also contained detectable acyl-CoA:sn-glycero-3-phosphate acyltransferase activity and the ability to potentiate the Ca++-stimulated exchange of bases between different phospholipids. These findings indicate that the bile canalicular membranes have a very limited capacity for the formation of phosphatidylcholine under the assay conditions employed.", "contents": "Activity of phospholipid-synthesizing enzymes in rat liver plasma membranes and the source of biliary lecithin. The potential for the synthesis of phosphatidylcholine by the bile canalicular membrane of the liver cell was assessed by measuring the activity of a number of phospholipid synthesizing enzymes in isolated bile canalicular membrane fractions from rat liver. The activity of these various enzymes was compared to that present in noncanalicular liver cell plasma membranes and in microsomes. The CDP-choline:1,2-diacyl-sn-glycerol-cholinephosphotransferase was virtually absent from the bile canalicular membranes but the specific activities of S-adenosyl-L-methionine:phosphatidyl-ethanolamine N-methyltransferase and acyl-CoA:1-acyl-sn-glycero-3-phosphorylcholine acyltransferase were 11-15% of those found in the microsomes. The bile canalicular membranes also contained detectable acyl-CoA:sn-glycero-3-phosphate acyltransferase activity and the ability to potentiate the Ca++-stimulated exchange of bases between different phospholipids. These findings indicate that the bile canalicular membranes have a very limited capacity for the formation of phosphatidylcholine under the assay conditions employed."}
{"id": "PMID:191717", "title": "Origin of fatty acids of cholesteryl ester accumulated by Fu5AH cells in culture.", "content": "The Fu5AH rat hepatoma cell line accumulates cholesteryl ester (CE) upon incubation in medium supplemented with hyperlipemic serum or hyperlipemic serum lipoproteins. This cell line was used to investigate the origin of the fatty acids esterified to cholesterol in intracellular accumulations of CE. The intracellular CE-fatty acid distribution was found to be markedly different from that of the lipoprotein which stimulated the accumulation. Free fatty acids added to the culture medium were found esterified to cholesterol in the cells, demonstrating that cellular esterification contributes to the accumulation of CE. Using a subline of Fu5AH cells containing radioactivity labeled intracellular fatty acids, it was found that about one-third of the fatty acid moiety of CE accumulated by the cells during a 24 hr incubation with hyperlipemic serum was derived from endogenous fatty acids. The drug chloroquine was found to inhibit cellular cholesterol esterification, so that only 4% of CE-fatty acids were derived from endogenous fatty acids. Evidence is presented suggesting a major role for cellular esterification in CE accumulation by Fu5AH cells.", "contents": "Origin of fatty acids of cholesteryl ester accumulated by Fu5AH cells in culture. The Fu5AH rat hepatoma cell line accumulates cholesteryl ester (CE) upon incubation in medium supplemented with hyperlipemic serum or hyperlipemic serum lipoproteins. This cell line was used to investigate the origin of the fatty acids esterified to cholesterol in intracellular accumulations of CE. The intracellular CE-fatty acid distribution was found to be markedly different from that of the lipoprotein which stimulated the accumulation. Free fatty acids added to the culture medium were found esterified to cholesterol in the cells, demonstrating that cellular esterification contributes to the accumulation of CE. Using a subline of Fu5AH cells containing radioactivity labeled intracellular fatty acids, it was found that about one-third of the fatty acid moiety of CE accumulated by the cells during a 24 hr incubation with hyperlipemic serum was derived from endogenous fatty acids. The drug chloroquine was found to inhibit cellular cholesterol esterification, so that only 4% of CE-fatty acids were derived from endogenous fatty acids. Evidence is presented suggesting a major role for cellular esterification in CE accumulation by Fu5AH cells."}
{"id": "PMID:191718", "title": "Lipids of cultured hepatoma cells: VIII. Utilization of D-[1-14C] glucose for lipid biosynthesis.", "content": "Minimal deviation hepatoma 7288C cells (HTC) were incubated in serum-supplemented and serum-free Swim's 77 medium in the presence of D-[1-14C] glucose for 1, 2, 4, 8, 12 and 24 hr. Glucose oxidation to CO2, incorporation into total cell mass, and incorporation into cell and medium lipids were determined. The percentage distribution of total cell lipid radioactivity in individual neutral and polar lipid classes was followed as a function of time. Degradation studies of individual lipid classes were performed to ascertain the percentage of radioactivity in acyl and glycerol moieties. The percentage of D-[1-14C] glucose oxidized to 14CO2, incorporated into cell matter and cell lipids was elevated in cells incubated in serum-free medium as opposed to serum-supplemented medium. The percentage distribution of total cell lipid radioactivity into individual neutral lipid classes from both serum-free and serum-supplemented cultures was as follows: sterols greater than triglycerides greater than free fatty acids greater than sterol esters. The percentage distribution of total cell lipid radioactivity into individual polar lipid classes of serum-supplemented cultures was as follows: phosphatidylcholine greater than phosphatidylinositol greater than sphingomyelin greater than phosphatidylethanolamine greater than phosphatidylserine. The distribution of glucose radiolabel into individual polar lipid classes of serum-free HTC cells was different from their serum-supplemented counterparts: sphingomyelin greater than phosphatidylcholine greater than phosphatidylinositol greater than phosphatidylethanolamine greater than phosphatidylserine. Glycerol from glyceride classes contained a higher percentage of radioactivity than the acyl moieties, with this percentage significantly elevated in serum-free cultures. The data indicate that, although glucose is a substrate for HTC cell lipids, other precursors present in the culture system also contribute to the lipid constituency of this hepatoma cell line.", "contents": "Lipids of cultured hepatoma cells: VIII. Utilization of D-[1-14C] glucose for lipid biosynthesis. Minimal deviation hepatoma 7288C cells (HTC) were incubated in serum-supplemented and serum-free Swim's 77 medium in the presence of D-[1-14C] glucose for 1, 2, 4, 8, 12 and 24 hr. Glucose oxidation to CO2, incorporation into total cell mass, and incorporation into cell and medium lipids were determined. The percentage distribution of total cell lipid radioactivity in individual neutral and polar lipid classes was followed as a function of time. Degradation studies of individual lipid classes were performed to ascertain the percentage of radioactivity in acyl and glycerol moieties. The percentage of D-[1-14C] glucose oxidized to 14CO2, incorporated into cell matter and cell lipids was elevated in cells incubated in serum-free medium as opposed to serum-supplemented medium. The percentage distribution of total cell lipid radioactivity into individual neutral lipid classes from both serum-free and serum-supplemented cultures was as follows: sterols greater than triglycerides greater than free fatty acids greater than sterol esters. The percentage distribution of total cell lipid radioactivity into individual polar lipid classes of serum-supplemented cultures was as follows: phosphatidylcholine greater than phosphatidylinositol greater than sphingomyelin greater than phosphatidylethanolamine greater than phosphatidylserine. The distribution of glucose radiolabel into individual polar lipid classes of serum-free HTC cells was different from their serum-supplemented counterparts: sphingomyelin greater than phosphatidylcholine greater than phosphatidylinositol greater than phosphatidylethanolamine greater than phosphatidylserine. Glycerol from glyceride classes contained a higher percentage of radioactivity than the acyl moieties, with this percentage significantly elevated in serum-free cultures. The data indicate that, although glucose is a substrate for HTC cell lipids, other precursors present in the culture system also contribute to the lipid constituency of this hepatoma cell line."}
{"id": "PMID:191719", "title": "A comparison of simplified methods for lipoprotein quantification using the analytic ultracentrifuge as a standard.", "content": "Two simplified methods for quantitative lipoprotein analysis have been calibrated and compared with each other using analytic ultracentrifugation as a standard reference procedure. The first method was the Friedewald procedure and the second was an automated agarose gel electrophoresis system. Both procedures offer comparable quantitative lipoprotein analysis with potential for large scale screening purposes at low cost ($4.00-$5.00 per analysis). There were advantages and limitations to both procedures. The Friedwald procedure can be used on frozen sera but requires 3 ml sera. In contrast, the electrophoresis system must be used with fresh serum but requires only 50 mul serum and the electrophoretic slides may be quantitatively analyzed several years retrospectively.", "contents": "A comparison of simplified methods for lipoprotein quantification using the analytic ultracentrifuge as a standard. Two simplified methods for quantitative lipoprotein analysis have been calibrated and compared with each other using analytic ultracentrifugation as a standard reference procedure. The first method was the Friedewald procedure and the second was an automated agarose gel electrophoresis system. Both procedures offer comparable quantitative lipoprotein analysis with potential for large scale screening purposes at low cost ($4.00-$5.00 per analysis). There were advantages and limitations to both procedures. The Friedwald procedure can be used on frozen sera but requires 3 ml sera. In contrast, the electrophoresis system must be used with fresh serum but requires only 50 mul serum and the electrophoretic slides may be quantitatively analyzed several years retrospectively."}
{"id": "PMID:191720", "title": "The effect of a short term saturated fat diet on the apoprotein composition and radioiodination properties of rat very low density lipoproteins.", "content": "The effect of a saturated fat diet on the apoprotein composition and radioiodination properties of plasma very low density lipoprotein (VLDL) was studied in rats. After feeding the diet for 10 days, the proportion of 125I attached to VLDL lipid decreased from 50% (control animals) to 8%, the remainder (92%) being bound to the apoprotein components. The decreased lipid labelling was associated with proportional changes in the fatty acid composition of serum and VLDL lipids, the most notable change being a reduction in linoleic acid (30-8%) content which occurred in all the major lipid classes of both serum and VLDL. Analysis of VLDL after radioiodination showed that most of the radioactivity incorporated into the lipid moiety was associated with phospholipid. The proportion of 125I bound to phospholipid decreased after feeding rats a saturated diet. The proportion of soluble (small molecular weight peptides and arginine rich peptide) to insoluble (B apoprotein) did not alter during the saturated fatty acid dietary regime and no differences in the distribution of soluble proteins were observed. It is concluded that feeding a saturated fat diet to rats for 10 days significantly improved 125I labelling of the apoprotein moiety while apparently not inducing changes in apoprotein composition.", "contents": "The effect of a short term saturated fat diet on the apoprotein composition and radioiodination properties of rat very low density lipoproteins. The effect of a saturated fat diet on the apoprotein composition and radioiodination properties of plasma very low density lipoprotein (VLDL) was studied in rats. After feeding the diet for 10 days, the proportion of 125I attached to VLDL lipid decreased from 50% (control animals) to 8%, the remainder (92%) being bound to the apoprotein components. The decreased lipid labelling was associated with proportional changes in the fatty acid composition of serum and VLDL lipids, the most notable change being a reduction in linoleic acid (30-8%) content which occurred in all the major lipid classes of both serum and VLDL. Analysis of VLDL after radioiodination showed that most of the radioactivity incorporated into the lipid moiety was associated with phospholipid. The proportion of 125I bound to phospholipid decreased after feeding rats a saturated diet. The proportion of soluble (small molecular weight peptides and arginine rich peptide) to insoluble (B apoprotein) did not alter during the saturated fatty acid dietary regime and no differences in the distribution of soluble proteins were observed. It is concluded that feeding a saturated fat diet to rats for 10 days significantly improved 125I labelling of the apoprotein moiety while apparently not inducing changes in apoprotein composition."}
{"id": "PMID:191723", "title": "Black-white similarities in cord blood lipids and lipoproteins.", "content": "Cord blood lipoproteins were quantitated in 117 neonates (58 white, 50 black) to assess for potential early expression of racial lipid distinctions. In comparison of black and white neonates there were no differences in total cholesterol (TC), high-density lipoprotein cholesterol (C-HDL), low-density lipoprotein cholesterol (C-LDL), C-HDL/C-LDL, or C-HDL/TC. Cord blood triglycerides were slightly higher in black neonates (p = 0.02). Unlike certain adult black-white comparisons and within the limits of \"genicity\" as expressed by cord blood lipoproteins, there were no racial differences in C-HDL, C-LDL, and total cholesterol.", "contents": "Black-white similarities in cord blood lipids and lipoproteins. Cord blood lipoproteins were quantitated in 117 neonates (58 white, 50 black) to assess for potential early expression of racial lipid distinctions. In comparison of black and white neonates there were no differences in total cholesterol (TC), high-density lipoprotein cholesterol (C-HDL), low-density lipoprotein cholesterol (C-LDL), C-HDL/C-LDL, or C-HDL/TC. Cord blood triglycerides were slightly higher in black neonates (p = 0.02). Unlike certain adult black-white comparisons and within the limits of \"genicity\" as expressed by cord blood lipoproteins, there were no racial differences in C-HDL, C-LDL, and total cholesterol."}
{"id": "PMID:191724", "title": "Urinary excretion of carnitine and serum concentrations of carnitine and lipids in patients with hypofunctional endocrine diseases: involvement of adrenocorticoid and thyroid hormones in ACTH-induced augmentation of carnitine and lipids metabolism.", "content": "The promoting effect of ACTH on carnitine and lipid metabolism was studied in patients with various endocrine hypofunctions. The results were compared with those of normal subjects. In adrenocortical insufficiency, hypothyroidism and hypopituitarism urinary excretion of carnitine was significantly lower than in normal subjects. On intramuscular injection of synthetic beta1-24 ACTH-Z urninary excretion of carnitine in normal subjects increased sixfold on the day of the injection and returned to the pretreatment level on the third day. Serum concentrations of carnitine and FFA increase in parallel with carnitine excretion, while serum triglyceride was lowered in response to ACTH administration. These responses were totally lacking or substantially suppressed in patients with the above endocrine insufficiencies. In hypothyroid and hypopituitary patients substitution therapy restored the responses to ACTH in the same fashion as those in normal subjects. These findings suggest that the promoting effect of ACTH on carnitine and lipid metabolism requires the presence of intact adrenocortical and thyroid functions.", "contents": "Urinary excretion of carnitine and serum concentrations of carnitine and lipids in patients with hypofunctional endocrine diseases: involvement of adrenocorticoid and thyroid hormones in ACTH-induced augmentation of carnitine and lipids metabolism. The promoting effect of ACTH on carnitine and lipid metabolism was studied in patients with various endocrine hypofunctions. The results were compared with those of normal subjects. In adrenocortical insufficiency, hypothyroidism and hypopituitarism urinary excretion of carnitine was significantly lower than in normal subjects. On intramuscular injection of synthetic beta1-24 ACTH-Z urninary excretion of carnitine in normal subjects increased sixfold on the day of the injection and returned to the pretreatment level on the third day. Serum concentrations of carnitine and FFA increase in parallel with carnitine excretion, while serum triglyceride was lowered in response to ACTH administration. These responses were totally lacking or substantially suppressed in patients with the above endocrine insufficiencies. In hypothyroid and hypopituitary patients substitution therapy restored the responses to ACTH in the same fashion as those in normal subjects. These findings suggest that the promoting effect of ACTH on carnitine and lipid metabolism requires the presence of intact adrenocortical and thyroid functions."}
{"id": "PMID:191725", "title": "Mechanism of action of luteinizing hormone and follicle-stimulating hormone on the ovary in vitro.", "content": "The mechanism of action of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) upon various cell types of the mammalian ovary is reviewed. Emphasis is placed upon in vitro studies using organ and cell culture as well as short-term incubations. FSH and LH actions upon the following ovarian functions are discussed: steroidogenesis and metabolism of the ovary as a whole and of the isolated follicle and its component cell types, the granulosa and thecal cells, as well as folliculogenesis and follicular growth, oocyte maturation, follicular rupture, and corpus luteum maintenance and steroidogenesis. The roles of gonadotropin receptors, AMP, prostaglandins, protein kinase, and protein synthesis in these LH and FSH actions are discussed. Intra-ovarian regulation of LH and FSH action is reviewed, including a discussion of the possible roles of follicular fluid inhibitors upon oocyte maturation and granulosa cell luteinization.", "contents": "Mechanism of action of luteinizing hormone and follicle-stimulating hormone on the ovary in vitro. The mechanism of action of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) upon various cell types of the mammalian ovary is reviewed. Emphasis is placed upon in vitro studies using organ and cell culture as well as short-term incubations. FSH and LH actions upon the following ovarian functions are discussed: steroidogenesis and metabolism of the ovary as a whole and of the isolated follicle and its component cell types, the granulosa and thecal cells, as well as folliculogenesis and follicular growth, oocyte maturation, follicular rupture, and corpus luteum maintenance and steroidogenesis. The roles of gonadotropin receptors, AMP, prostaglandins, protein kinase, and protein synthesis in these LH and FSH actions are discussed. Intra-ovarian regulation of LH and FSH action is reviewed, including a discussion of the possible roles of follicular fluid inhibitors upon oocyte maturation and granulosa cell luteinization."}
{"id": "PMID:191726", "title": "Neonatal familial hyperalphalipoproteinemia.", "content": "A kindred with four-generation vertical transmission of familial hyperalphalipoproteinemia was ascertained by measurement of elevated levels of cord blood high-density lipoprotein cholesterol (C-HDL) in a neonatal propositus. Quantitation of cord blood C-HDL coupled with family studies and longitudinal follow-up allows the diagnosis of familial hyperalphalipoproteinemia in infancy.", "contents": "Neonatal familial hyperalphalipoproteinemia. A kindred with four-generation vertical transmission of familial hyperalphalipoproteinemia was ascertained by measurement of elevated levels of cord blood high-density lipoprotein cholesterol (C-HDL) in a neonatal propositus. Quantitation of cord blood C-HDL coupled with family studies and longitudinal follow-up allows the diagnosis of familial hyperalphalipoproteinemia in infancy."}
{"id": "PMID:191727", "title": "Catecholamine inhibition of thyrotropin-induced secretion of thyroxine: mediation by an alpha-adrenergic receptor.", "content": "Thyroxine secretion by mouse thyroid gland incubated in vitro was measured. Thyrotropin or dibutyryl cAMP increased thyroxine secretion several-fold. l-Epinephrine and l-norepinephrine strongly inhibited this stimulated release; l-isoproterenol was relatively ineffective. Phentolamine prevented the inhibition by catecholamines of thyroxine release; l-propranolol had no effect. These findings indicate that stimulation of alpha-adrenergic receptors opposes the action of thyrotropin in the regulation of thyroxine secretion.", "contents": "Catecholamine inhibition of thyrotropin-induced secretion of thyroxine: mediation by an alpha-adrenergic receptor. Thyroxine secretion by mouse thyroid gland incubated in vitro was measured. Thyrotropin or dibutyryl cAMP increased thyroxine secretion several-fold. l-Epinephrine and l-norepinephrine strongly inhibited this stimulated release; l-isoproterenol was relatively ineffective. Phentolamine prevented the inhibition by catecholamines of thyroxine release; l-propranolol had no effect. These findings indicate that stimulation of alpha-adrenergic receptors opposes the action of thyrotropin in the regulation of thyroxine secretion."}
{"id": "PMID:191736", "title": "Hepatocelluilar carcinoma: a possible complication of oral contraceptive steroids.", "content": "A patient was found to have developed a primary hepatocellular carcinoma after taking an oral contraceptive steroid preparation for four years. After resection of the tumour over five years ago, and resumption of the birth control Pill, a recurrent hepatocellular caricnoma has developed. The risk of this complicationis extremely small and appears to be related to the duration of ingestion of the drug and to the amount of oestrogen present in the preparation used. The modes of presentation of these tumours and the methods of investigation are outlined, and the high incidence of spontaneous rupture causing life-threatening intraperitoneal haemorrhage is emphasized.", "contents": "Hepatocelluilar carcinoma: a possible complication of oral contraceptive steroids. A patient was found to have developed a primary hepatocellular carcinoma after taking an oral contraceptive steroid preparation for four years. After resection of the tumour over five years ago, and resumption of the birth control Pill, a recurrent hepatocellular caricnoma has developed. The risk of this complicationis extremely small and appears to be related to the duration of ingestion of the drug and to the amount of oestrogen present in the preparation used. The modes of presentation of these tumours and the methods of investigation are outlined, and the high incidence of spontaneous rupture causing life-threatening intraperitoneal haemorrhage is emphasized."}
{"id": "PMID:191737", "title": "Hepatocellular carcinoma in association with androgen therapy.", "content": "The case of a young man with hypogonadism, who was treated for five years withmethyltestosterone and who developed hepatocellular carcinoma, is discussed. He received a course of 5-fluorouracil via the hepatic artery. Complete regression has been maintained for four years. It is likely that the androgen therapy is implicated in the development of the liver tumour. Recent reports of untoward effects of steroid hormones are reviewed.", "contents": "Hepatocellular carcinoma in association with androgen therapy. The case of a young man with hypogonadism, who was treated for five years withmethyltestosterone and who developed hepatocellular carcinoma, is discussed. He received a course of 5-fluorouracil via the hepatic artery. Complete regression has been maintained for four years. It is likely that the androgen therapy is implicated in the development of the liver tumour. Recent reports of untoward effects of steroid hormones are reviewed."}
{"id": "PMID:191738", "title": "An extensive rotavirus outbreak in aboriginal infants in central Australia.", "content": "Faecal specimens were obtained from 92 Aboriginal infants admitted to Alice Springs Hospital during an extensive outbreak of gastroenteritis in the surrounding area in July, 1976. Specimens were examined for potentially pathogenic viruses, bacteria and parasites. Rotavirus proved to be by far the most common potential pathogen, being detected in 54% of specimens.", "contents": "An extensive rotavirus outbreak in aboriginal infants in central Australia. Faecal specimens were obtained from 92 Aboriginal infants admitted to Alice Springs Hospital during an extensive outbreak of gastroenteritis in the surrounding area in July, 1976. Specimens were examined for potentially pathogenic viruses, bacteria and parasites. Rotavirus proved to be by far the most common potential pathogen, being detected in 54% of specimens."}
{"id": "PMID:191745", "title": "[Diagnostic significance of identification of anti-entamoeba histolytica antibodies (author's transl)].", "content": "Examinations were performed with the indirect immunofluorescence test (IFAT) and the indirect haemagglutination test (IHAT). Negative titers (less than 1:5) do not exclude an infection with E. histolytica. Titers up to 1:80 in both reactions are found in patients with negative stool specimens or indicate an asymptomatic infection of the intestinal lumen, an incipient or past symptomatic amoebiasis. IFAT values of 1:160 together with a negative or positive IHAT are also suggestive of the two last-mentioned types of infection. These titers are also found in patients with gastrointestinal disorders of other orgin. IFAT values higher than 1:60 with a positive IHAT are probably due to an invasive amoebiasis. Titres are, however, only diagnostic pointers.", "contents": "[Diagnostic significance of identification of anti-entamoeba histolytica antibodies (author's transl)]. Examinations were performed with the indirect immunofluorescence test (IFAT) and the indirect haemagglutination test (IHAT). Negative titers (less than 1:5) do not exclude an infection with E. histolytica. Titers up to 1:80 in both reactions are found in patients with negative stool specimens or indicate an asymptomatic infection of the intestinal lumen, an incipient or past symptomatic amoebiasis. IFAT values of 1:160 together with a negative or positive IHAT are also suggestive of the two last-mentioned types of infection. These titers are also found in patients with gastrointestinal disorders of other orgin. IFAT values higher than 1:60 with a positive IHAT are probably due to an invasive amoebiasis. Titres are, however, only diagnostic pointers."}
{"id": "PMID:191747", "title": "Development and applications of Bacillus subtilis test systems for mutagens, involving DNA-repair deficiency and suppressible auxotrophic mutations.", "content": "A mutagen-tester of Bacillus subtilis was constructed and tested with known carcinogens. The parental strain HA101 of Okubo and Yanagida carrying suppressible nonsense mutations in his and met genes was transformed to carry an excision-repair deficiency mutation. The constructed strain TKJ5211 showed a 20--30-fold higher sensitivity for His+ reversion than the parental strain when treated with UV and UV-mimetic chemicals but unchanged mutation frequency with X-rays and methyl methanesulfonate. The tester strain was used in a spot test of 30 selected chemicals and also for testing with liver homogenate activation. The results showed an almost equivalent but somewhat broader detection spectrum than the Salmonella typhimurium TA100 system. Another test method used a pair of B. subtilis strains differing in their DNA-repair capacity, i.e. the most UV-sensitive mutant HJ-15 and a wild-type strain, to detect repair-dependent DNA damage produced by chemicals. Spores could be used in either test.", "contents": "Development and applications of Bacillus subtilis test systems for mutagens, involving DNA-repair deficiency and suppressible auxotrophic mutations. A mutagen-tester of Bacillus subtilis was constructed and tested with known carcinogens. The parental strain HA101 of Okubo and Yanagida carrying suppressible nonsense mutations in his and met genes was transformed to carry an excision-repair deficiency mutation. The constructed strain TKJ5211 showed a 20--30-fold higher sensitivity for His+ reversion than the parental strain when treated with UV and UV-mimetic chemicals but unchanged mutation frequency with X-rays and methyl methanesulfonate. The tester strain was used in a spot test of 30 selected chemicals and also for testing with liver homogenate activation. The results showed an almost equivalent but somewhat broader detection spectrum than the Salmonella typhimurium TA100 system. Another test method used a pair of B. subtilis strains differing in their DNA-repair capacity, i.e. the most UV-sensitive mutant HJ-15 and a wild-type strain, to detect repair-dependent DNA damage produced by chemicals. Spores could be used in either test."}
{"id": "PMID:191748", "title": "Repair of single-strand DNA breaks and recovery of chromosomal and chromatid aberrations after treatment of plant seeds with propyl methanesulfonate in vivo.", "content": "Repair of single-strand breaks of DNA and simultaneous recovery of chromosomal aberrations were studied after treatment of barley seeds with the monofunctional alkylating chemical mutagen, propyl methanesulfonate in vivo. In soaked seeds the diminution of single-strand breaks of DNA induced by PMS was correlated with the decrease of chromosomal aberrations, whereas in dried seeds the repair of DNA breaks was depressed and, in accord with this, the frequency of chromosomal aberrations increased. The prolonged storage of seeds led to a more delayed repair of chromosomal aberrations in dry seeds and a more delayed accelerated repair in soaked seeds.", "contents": "Repair of single-strand DNA breaks and recovery of chromosomal and chromatid aberrations after treatment of plant seeds with propyl methanesulfonate in vivo. Repair of single-strand breaks of DNA and simultaneous recovery of chromosomal aberrations were studied after treatment of barley seeds with the monofunctional alkylating chemical mutagen, propyl methanesulfonate in vivo. In soaked seeds the diminution of single-strand breaks of DNA induced by PMS was correlated with the decrease of chromosomal aberrations, whereas in dried seeds the repair of DNA breaks was depressed and, in accord with this, the frequency of chromosomal aberrations increased. The prolonged storage of seeds led to a more delayed repair of chromosomal aberrations in dry seeds and a more delayed accelerated repair in soaked seeds."}
{"id": "PMID:191762", "title": "Nephritogenic glycoprotein. V. Immunochemical studies on nephritogenic activity of collagenase and pronase-digests prepared from various rat organs.", "content": "A new immunochemical procedure was introduced to estimate the nephritogenic activity of collagenase and pronase digests of various rat organs. A glycoprotein isolated from collagenase digests of various rat organs showed the nephritogenic activity as well as the antigenic activity that induces nephrotoxic antibody, which were nearly identical to those of a glycoprotein isolated from trypsin digests of the rat organ concerned. A glycoprotein isolated from pronase digests of various rat organs was proved to have no antigenic activity that induces nephrotoxic antibody, but the existence of nephritogenic activity was proved in this glycoprotein. These results were supported firmly by the assay experiments for nephritogenicity. Ouchterlony gel diffusion test and the assay experiments demonstrated the existence of a common nephritogenic substance among the glycoproteins isolated from trypsin, collagenase and pronase digests of rat organs.", "contents": "Nephritogenic glycoprotein. V. Immunochemical studies on nephritogenic activity of collagenase and pronase-digests prepared from various rat organs. A new immunochemical procedure was introduced to estimate the nephritogenic activity of collagenase and pronase digests of various rat organs. A glycoprotein isolated from collagenase digests of various rat organs showed the nephritogenic activity as well as the antigenic activity that induces nephrotoxic antibody, which were nearly identical to those of a glycoprotein isolated from trypsin digests of the rat organ concerned. A glycoprotein isolated from pronase digests of various rat organs was proved to have no antigenic activity that induces nephrotoxic antibody, but the existence of nephritogenic activity was proved in this glycoprotein. These results were supported firmly by the assay experiments for nephritogenicity. Ouchterlony gel diffusion test and the assay experiments demonstrated the existence of a common nephritogenic substance among the glycoproteins isolated from trypsin, collagenase and pronase digests of rat organs."}
{"id": "PMID:191763", "title": "Interaction between parathyroid hormone and catecholamines on renal cortical cyclic AMP.", "content": "Parathyroid hormone (PTH) and catecholamines (CA) increased cAMP levels in isolated tubules of rat renal cortex. A rise in cAMP could be detected 10 sec after the addition of agonists, and it reached the peak in 30-60 sec and then decreased despite the presence of active agonists. Direct relationships exist between theophylline concentrations and cAMP levels in response to agonists. Three- to fivefold rises in cAMP levels were observed with a maximal dose of PTH compared with that of CA, and there was no additive effect. Both PTH and CA stimulated renal gluconeogenesis; when added together with each maximal dose, no additive effect was observed. These results suggest the important role of phosphodiesterase to control tubular cAMP in response to hormonal stimuli, and there is a tubule cell group responding to both PTH and CA.", "contents": "Interaction between parathyroid hormone and catecholamines on renal cortical cyclic AMP. Parathyroid hormone (PTH) and catecholamines (CA) increased cAMP levels in isolated tubules of rat renal cortex. A rise in cAMP could be detected 10 sec after the addition of agonists, and it reached the peak in 30-60 sec and then decreased despite the presence of active agonists. Direct relationships exist between theophylline concentrations and cAMP levels in response to agonists. Three- to fivefold rises in cAMP levels were observed with a maximal dose of PTH compared with that of CA, and there was no additive effect. Both PTH and CA stimulated renal gluconeogenesis; when added together with each maximal dose, no additive effect was observed. These results suggest the important role of phosphodiesterase to control tubular cAMP in response to hormonal stimuli, and there is a tubule cell group responding to both PTH and CA."}
{"id": "PMID:191765", "title": "Adrenal cortical secretory responses to histamine and cyanide in dogs with hypothalamic lesions.", "content": "Experiments were performed on dogs with hypothalamic lesions as well as on intact and hypophysectomized dogs. Adrenal venous blood samples were collected and analyzed for 17-hydroxycorticosteroids (17-OHCS). In intact dogs, a marked increase in adrenal 17-OHCS secretion was observed after an i.v. injection of histamine and following an i.v. infusion of cyanide. Adrenal 17-OHCS secretion in response to histamine was markedly reduced but not completely abolished by hypophysectomy and was partially impaired by anterior median eminence lesions and by posterior median eminence lesions, but was not significantly impaired by supramammillary lesions. Adrenal 17-OHCS secretion in response to cyanide was completely abolished by hypophysectomy, markedly reduced by posterior median eminence lesions and partially impaired by anterior median eminence lesions and by supramammillary lesions. Thus, a partial dissociation of the adrenocortical secretory responses to histamine and cyanide was observed in dogs with hypothalamic lesions, suggesting that the mechanism and the pathway to the anterior pituitary involved in the adrenocortical secretory response to histamine and cyanide are somewhat different.", "contents": "Adrenal cortical secretory responses to histamine and cyanide in dogs with hypothalamic lesions. Experiments were performed on dogs with hypothalamic lesions as well as on intact and hypophysectomized dogs. Adrenal venous blood samples were collected and analyzed for 17-hydroxycorticosteroids (17-OHCS). In intact dogs, a marked increase in adrenal 17-OHCS secretion was observed after an i.v. injection of histamine and following an i.v. infusion of cyanide. Adrenal 17-OHCS secretion in response to histamine was markedly reduced but not completely abolished by hypophysectomy and was partially impaired by anterior median eminence lesions and by posterior median eminence lesions, but was not significantly impaired by supramammillary lesions. Adrenal 17-OHCS secretion in response to cyanide was completely abolished by hypophysectomy, markedly reduced by posterior median eminence lesions and partially impaired by anterior median eminence lesions and by supramammillary lesions. Thus, a partial dissociation of the adrenocortical secretory responses to histamine and cyanide was observed in dogs with hypothalamic lesions, suggesting that the mechanism and the pathway to the anterior pituitary involved in the adrenocortical secretory response to histamine and cyanide are somewhat different."}
{"id": "PMID:191766", "title": "Plasma glucocorticoid elevation and ultrastructural changes in the adenohypophysis of the male rat following prolonged exposure to stress.", "content": "A morphological and ultrastructural study is described which indicates that cellular activity in the adenohypophysis correlates well with the circulating levels of corticosterone. Intense secretory activity is observed in all tropic cells of the adenohypophysis over 10 days; thereafter the cellular morphology shows a return to the control condition. There are, however, differences in the degree of adaptation between the different tropic cells. After its initial hyperactivity, corticotrope activity returned to a control level by 20 days. Thyrotrope activity was also found to adapt to control activity, but only after 40 days. Similar patterns were observed in the stomatotrope and gonadotrope, where the initial hypertrophy returned to control levels by 20 days; thereafter, however, an inhibition was observed. The luteotrope however, seems to be an exception in that its level of activity increased throughout the duration of the stress procedure.", "contents": "Plasma glucocorticoid elevation and ultrastructural changes in the adenohypophysis of the male rat following prolonged exposure to stress. A morphological and ultrastructural study is described which indicates that cellular activity in the adenohypophysis correlates well with the circulating levels of corticosterone. Intense secretory activity is observed in all tropic cells of the adenohypophysis over 10 days; thereafter the cellular morphology shows a return to the control condition. There are, however, differences in the degree of adaptation between the different tropic cells. After its initial hyperactivity, corticotrope activity returned to a control level by 20 days. Thyrotrope activity was also found to adapt to control activity, but only after 40 days. Similar patterns were observed in the stomatotrope and gonadotrope, where the initial hypertrophy returned to control levels by 20 days; thereafter, however, an inhibition was observed. The luteotrope however, seems to be an exception in that its level of activity increased throughout the duration of the stress procedure."}
{"id": "PMID:191767", "title": "Morphological aspects of the vessels of brain tumours.", "content": "The vascular changes associated with cerebral tumours are demonstrated angiographically and histologically.", "contents": "Morphological aspects of the vessels of brain tumours. The vascular changes associated with cerebral tumours are demonstrated angiographically and histologically."}
{"id": "PMID:191768", "title": "Lack of association between defective delinquents and antibody of herpesvirus hominis.", "content": "Several groups have reported a relation between herpesvirus hominis infection and certain psychiatric disorders. We have investigated herpes antibody levels in chronic criminal offenders who were diagnosed as defective delinquents and in criminals who were not defective delinquents. We found no difference in the frequency of titers of herpesvirus type I or type 2 antibody in these groups.", "contents": "Lack of association between defective delinquents and antibody of herpesvirus hominis. Several groups have reported a relation between herpesvirus hominis infection and certain psychiatric disorders. We have investigated herpes antibody levels in chronic criminal offenders who were diagnosed as defective delinquents and in criminals who were not defective delinquents. We found no difference in the frequency of titers of herpesvirus type I or type 2 antibody in these groups."}
{"id": "PMID:191769", "title": "[Observations on the therapy of endothoracic sarcoidosis with ACTH].", "content": "The Author on the basis of data obtained with ACTH treatment in endothoracic sarcoidosis concludes that the administration of corticotrophin is advisable mainly when an intolerability to corticosteroids is present or when corticosteroid therapy does not display any appreciable effect. When steroid treatment yields partially satisfactory results, ACTH administration can produce further improvements.", "contents": "[Observations on the therapy of endothoracic sarcoidosis with ACTH]. The Author on the basis of data obtained with ACTH treatment in endothoracic sarcoidosis concludes that the administration of corticotrophin is advisable mainly when an intolerability to corticosteroids is present or when corticosteroid therapy does not display any appreciable effect. When steroid treatment yields partially satisfactory results, ACTH administration can produce further improvements."}
{"id": "PMID:191770", "title": "[Behavior of blood lipids and lipoproteins in myocardial infarct].", "content": "Blood lipids and lipoproteins were evaluated in male and female subjects of various ages with acute myocardial infarct. Values were within the limits of normal in less than 50%, mostly in the aged. II B (24%), IV (18%) and II A (11%) lipoprotidaemic pictures were the most common. It is felt that abnormal values are not necessarily part of the infarct picture; if present, they are mainly of the II B type.", "contents": "[Behavior of blood lipids and lipoproteins in myocardial infarct]. Blood lipids and lipoproteins were evaluated in male and female subjects of various ages with acute myocardial infarct. Values were within the limits of normal in less than 50%, mostly in the aged. II B (24%), IV (18%) and II A (11%) lipoprotidaemic pictures were the most common. It is felt that abnormal values are not necessarily part of the infarct picture; if present, they are mainly of the II B type."}
{"id": "PMID:191771", "title": "Herpes simplex virus type 2 meningitis.", "content": "To date only 9 culture-proven cases of herpes simplex virus Type 2 meningitis have been recorded. Presented here is the 10th case with a review of the literature. Although generally a benign disease, its recognition in association with herpes progenitalis must be appreciated to avoid confusion in the treatment of this common veneral disease.", "contents": "Herpes simplex virus type 2 meningitis. To date only 9 culture-proven cases of herpes simplex virus Type 2 meningitis have been recorded. Presented here is the 10th case with a review of the literature. Although generally a benign disease, its recognition in association with herpes progenitalis must be appreciated to avoid confusion in the treatment of this common veneral disease."}
{"id": "PMID:191772", "title": "Herpes zoster ophthalmicus.", "content": "Herpes zoster ophthalmicus is not an uncommon disease and is more prevalent among debilitated and seriously ill patients. It is caused by the same virus causing varicella. The exact trigger mechanism is unknown, as well as much of the pathogenesis. The disease is more uncommon among the elderly and usually runs a benign course. Approximately 50% of the patients develop ocular complications ,the most frequent of these being keratitis, iritis, secondary glaucoma and extraocular muscle involvement. The most striking pathologic features are the lymphocytic infiltration of the long ciliary nerves and the vasculitis of the vessels accompanying them. The most controversial aspect of the disease is that of treatment. Almost every therapeutic regimen has been attempted in a disease whose natural course is self-limited. The future will add more to our knowledge of the pathogenesis of the disease and shed more light on the efficacy of various treatments.", "contents": "Herpes zoster ophthalmicus. Herpes zoster ophthalmicus is not an uncommon disease and is more prevalent among debilitated and seriously ill patients. It is caused by the same virus causing varicella. The exact trigger mechanism is unknown, as well as much of the pathogenesis. The disease is more uncommon among the elderly and usually runs a benign course. Approximately 50% of the patients develop ocular complications ,the most frequent of these being keratitis, iritis, secondary glaucoma and extraocular muscle involvement. The most striking pathologic features are the lymphocytic infiltration of the long ciliary nerves and the vasculitis of the vessels accompanying them. The most controversial aspect of the disease is that of treatment. Almost every therapeutic regimen has been attempted in a disease whose natural course is self-limited. The future will add more to our knowledge of the pathogenesis of the disease and shed more light on the efficacy of various treatments."}
{"id": "PMID:191773", "title": "Aniridia-Wilms' tumour syndrome.", "content": "The association of aniridia and Wilms' tumour constitutes a real syndrome, which is genetic. It may either be autosomal dominant or depend on a chromosomal deletion or also, according to Knudson's theory, be due to two mutational events, the initiating mutation being germinal and the promoting mutation being post-zygotical.", "contents": "Aniridia-Wilms' tumour syndrome. The association of aniridia and Wilms' tumour constitutes a real syndrome, which is genetic. It may either be autosomal dominant or depend on a chromosomal deletion or also, according to Knudson's theory, be due to two mutational events, the initiating mutation being germinal and the promoting mutation being post-zygotical."}
{"id": "PMID:191774", "title": "Prophylactic antibiotics in cataract surgery.", "content": "The value of preoperative cultures, sensitivity tests and prophylactic preoperative antibiotic treatment was evaluated in a group of senile, uncomplicated lens extractions. Sulfacetamide or a mixture of chloramphenicol and polymixin were applied preoperatively for 1 week and an injection of penicillin and streptomycin was given postoperatively. A control group of 140 cases without treatment was also studied. No postoperative infections developed in either group. The number of pathogenic cultures was significantly smaller in the treated group as compared with the untreated one; the mixture of chloramphenicol and polymixin B sulfate was found to be superior to sulfacetamide, different clinical data was compared in the two groups. No postoperative infections developed in either group.", "contents": "Prophylactic antibiotics in cataract surgery. The value of preoperative cultures, sensitivity tests and prophylactic preoperative antibiotic treatment was evaluated in a group of senile, uncomplicated lens extractions. Sulfacetamide or a mixture of chloramphenicol and polymixin were applied preoperatively for 1 week and an injection of penicillin and streptomycin was given postoperatively. A control group of 140 cases without treatment was also studied. No postoperative infections developed in either group. The number of pathogenic cultures was significantly smaller in the treated group as compared with the untreated one; the mixture of chloramphenicol and polymixin B sulfate was found to be superior to sulfacetamide, different clinical data was compared in the two groups. No postoperative infections developed in either group."}
{"id": "PMID:191775", "title": "Study on the pathogenesis of bluetongue: replication of the virus in the organs of infected sheep.", "content": "The pathogenesis of bluetongue infection was studied by the titration of the virus in tissue samples taken from sheep inoculated subcutaneously in the auricula of the ear with 76 TC ID50 of the plaque-purified type 10 bluetongue virus. Tissue samples were taken from individual animals killed at daily intervals over a period of 11 days. The mean incubation time was 6.9 days and the first clinical sign was pyrexia. On the 4th day, bluetongue virus was demonstrated in the lymph nodes of the cephalic area, tonsils and spleen; viraemia became demonstrable on the 6th day post-inoculation and typical macroscopic lesions due to the virus were first observed on the 8th day. It was concluded that, post-infection, the virus entered the regional lymph nodes. From there it was disseminated via the lymph and/or the blood stream to the lymphoid tissues in other parts of the body where further replication occurred. From these primary sites the virus was carried via the blood stream and infected the majority of tissues. Humoral antibody, as detected by immunofluorescence, did not appear to have a direct influence on the concentration of virus in solid tissues. Persistence of the virus in infected sheep was not demonstrated when tissues were taken 6, 8 and 16 weeks after infection.", "contents": "Study on the pathogenesis of bluetongue: replication of the virus in the organs of infected sheep. The pathogenesis of bluetongue infection was studied by the titration of the virus in tissue samples taken from sheep inoculated subcutaneously in the auricula of the ear with 76 TC ID50 of the plaque-purified type 10 bluetongue virus. Tissue samples were taken from individual animals killed at daily intervals over a period of 11 days. The mean incubation time was 6.9 days and the first clinical sign was pyrexia. On the 4th day, bluetongue virus was demonstrated in the lymph nodes of the cephalic area, tonsils and spleen; viraemia became demonstrable on the 6th day post-inoculation and typical macroscopic lesions due to the virus were first observed on the 8th day. It was concluded that, post-infection, the virus entered the regional lymph nodes. From there it was disseminated via the lymph and/or the blood stream to the lymphoid tissues in other parts of the body where further replication occurred. From these primary sites the virus was carried via the blood stream and infected the majority of tissues. Humoral antibody, as detected by immunofluorescence, did not appear to have a direct influence on the concentration of virus in solid tissues. Persistence of the virus in infected sheep was not demonstrated when tissues were taken 6, 8 and 16 weeks after infection."}
{"id": "PMID:191776", "title": "Kinetics of the IgM and IgG immunological response to sheep erythrocytes and bluetongue virus in mice.", "content": "The IgM and IgG response of mice to sheep erythrocytes (SRBC) and bluetongue virus (BTV) was determined by means of haemolytic plaque assays. Maximum primary IgM response to SRBC occurred after 4 days but declined rapidly to 4% of the maximum by Day 9. A lag period of about 2 days was observed in the appearance of IgG haemolytic plaque-forming cells (PFC) but they reached a maximum after 6-9 days. Secondary immunization resulted in the stimulation particularly of IgG PFC and from Day 6 onwards IgG predominated in the immunological response. The IgM response to BTV was remarkably similar to that observed when SRBC were used as antigen. IgG PFC, however, appeared within a day of the IgM, reaching a peak on Days 4-5. From then onwards, IgG PFC predominated in the response. At BTV concentrations of up to 10 mug per mouse, the virulent strain of BTV type 3 produced the weakest response. At higher antigen concentrations there was very little difference in the response to the serotypes tested, although the virulent strain of BTV type 4 tended to produce the strongest response.", "contents": "Kinetics of the IgM and IgG immunological response to sheep erythrocytes and bluetongue virus in mice. The IgM and IgG response of mice to sheep erythrocytes (SRBC) and bluetongue virus (BTV) was determined by means of haemolytic plaque assays. Maximum primary IgM response to SRBC occurred after 4 days but declined rapidly to 4% of the maximum by Day 9. A lag period of about 2 days was observed in the appearance of IgG haemolytic plaque-forming cells (PFC) but they reached a maximum after 6-9 days. Secondary immunization resulted in the stimulation particularly of IgG PFC and from Day 6 onwards IgG predominated in the immunological response. The IgM response to BTV was remarkably similar to that observed when SRBC were used as antigen. IgG PFC, however, appeared within a day of the IgM, reaching a peak on Days 4-5. From then onwards, IgG PFC predominated in the response. At BTV concentrations of up to 10 mug per mouse, the virulent strain of BTV type 3 produced the weakest response. At higher antigen concentrations there was very little difference in the response to the serotypes tested, although the virulent strain of BTV type 4 tended to produce the strongest response."}
{"id": "PMID:191777", "title": "The isolation and preliminary genetic classification of temperature-sensitive mutants of bluetongue virus.", "content": "Temperature-sensitive mutants of bluetongue virus were isolated and classified in 6 genetic recombination groups. The frequency of recombination varied both within and between groups. The 4 mutagens used viz. nitrous acid, N-methyl-N-nitroso-N-nitroguanidine, proflavine and 5-fluoro-uracil were found to differ in their efficacy. The period of incubation required for maximum recombination was 48 h at 28 degrees C.", "contents": "The isolation and preliminary genetic classification of temperature-sensitive mutants of bluetongue virus. Temperature-sensitive mutants of bluetongue virus were isolated and classified in 6 genetic recombination groups. The frequency of recombination varied both within and between groups. The 4 mutagens used viz. nitrous acid, N-methyl-N-nitroso-N-nitroguanidine, proflavine and 5-fluoro-uracil were found to differ in their efficacy. The period of incubation required for maximum recombination was 48 h at 28 degrees C."}
{"id": "PMID:191778", "title": "Glossopyrosis due to adenoid cystic carcinoma.", "content": "Glossopyrosis and glossodynia may occur from local or systemic factors or from any irritation along the course of the lingual nerve. Although cylindroma is relatively rare, it must be considered along with other malignant lesions when neurologic symptoms of burning and pain of the tongue persist. Examination of the lesion is best carried out as multiple needle biopsies rather than as open biopsy, in order to avoid seeding of the skin and lymphatics of the neck. Recurrences are frequent and, because of the slow growth, there must be a long follow-up period. Metastases to the lung and brain, although late, occur in large numbers of patients. Best results are obtained by a combination of radiation therapy and operation because the infiltration is so extensive that operation alone may not eliminate the tumor completely.", "contents": "Glossopyrosis due to adenoid cystic carcinoma. Glossopyrosis and glossodynia may occur from local or systemic factors or from any irritation along the course of the lingual nerve. Although cylindroma is relatively rare, it must be considered along with other malignant lesions when neurologic symptoms of burning and pain of the tongue persist. Examination of the lesion is best carried out as multiple needle biopsies rather than as open biopsy, in order to avoid seeding of the skin and lymphatics of the neck. Recurrences are frequent and, because of the slow growth, there must be a long follow-up period. Metastases to the lung and brain, although late, occur in large numbers of patients. Best results are obtained by a combination of radiation therapy and operation because the infiltration is so extensive that operation alone may not eliminate the tumor completely."}
{"id": "PMID:191779", "title": "[Infantile diarrhea and rotavirus (author's transl)].", "content": "The acute and convalescent sera of 328 children with acute enteritis were checked with the bovine diarrhea virus as antigen in complement fixation test. 13% had a seroconversion. Some cases were associated with skin rashes or signs of respiratory infection.", "contents": "[Infantile diarrhea and rotavirus (author's transl)]. The acute and convalescent sera of 328 children with acute enteritis were checked with the bovine diarrhea virus as antigen in complement fixation test. 13% had a seroconversion. Some cases were associated with skin rashes or signs of respiratory infection."}
{"id": "PMID:191780", "title": "[Residual dyslipoproteinemias after ethanol-weaning in alcoholic hyperlipidemic patients (author's transl)].", "content": "Twenty-two hyperlipidemic and long-term alcoholic patients were chosen as subjects with a chronic alcohol-dependent hyperlipoproteinemia, since their lipidemia was getting normal after they stopped alochol ingestion. After ethanol-weaning of these subjects, we found quantitative abnormalities of lipidemia (hypocholesterolemia in 5 cases among 22) and qualitative abnormal electrophoretic patterns in all cases: There is always a VLDL stain, a reduction of the LDL and VLDL migration. These facts suggest that exists in these patients a constant abnormality either in the enzymatic, or in the lipoprotein structures, which is induced or revealed by alcohol ingestion.20", "contents": "[Residual dyslipoproteinemias after ethanol-weaning in alcoholic hyperlipidemic patients (author's transl)]. Twenty-two hyperlipidemic and long-term alcoholic patients were chosen as subjects with a chronic alcohol-dependent hyperlipoproteinemia, since their lipidemia was getting normal after they stopped alochol ingestion. After ethanol-weaning of these subjects, we found quantitative abnormalities of lipidemia (hypocholesterolemia in 5 cases among 22) and qualitative abnormal electrophoretic patterns in all cases: There is always a VLDL stain, a reduction of the LDL and VLDL migration. These facts suggest that exists in these patients a constant abnormality either in the enzymatic, or in the lipoprotein structures, which is induced or revealed by alcohol ingestion.20"}
{"id": "PMID:191781", "title": "[Apolipoprotein abnormalities in low and very low density lipoproteins in a type V hyperlipemia (author's transl)].", "content": "Abnormalities in VLDL and LDL apolipoproteins have been observed in the serum of an 11 year old girl with a type V hyperlipoproteinemia (VLDL + chylomicrons). This was shown with polyacrylamide gel electrophoresis and also with two dimensional immunoelectrophoresis. The LDL contain peptides which are not found in normal apo LDL. In the VLDL, heterogeneity of the lipopeptides is more marked that in normal VLDL, and there is an abnormal distribution of the apolipoproteins C or D.", "contents": "[Apolipoprotein abnormalities in low and very low density lipoproteins in a type V hyperlipemia (author's transl)]. Abnormalities in VLDL and LDL apolipoproteins have been observed in the serum of an 11 year old girl with a type V hyperlipoproteinemia (VLDL + chylomicrons). This was shown with polyacrylamide gel electrophoresis and also with two dimensional immunoelectrophoresis. The LDL contain peptides which are not found in normal apo LDL. In the VLDL, heterogeneity of the lipopeptides is more marked that in normal VLDL, and there is an abnormal distribution of the apolipoproteins C or D."}
{"id": "PMID:191789", "title": "Deficient activity of hepatic pyruvate dehydrogenase and pyruvate carboxylase in Reye's syndrome.", "content": "The activity of certain hepatic enzymes involved in carbohydrate metabolism was measured in postmortem samples from six cases of Reye's syndrome. The activities of the two exclusively extramitochondrial enzymes, glucose-6-phosphatase and fructose-1,6-diphosphatase, were all within the normal range. Activities of pyruvate carboxylase and pyruvate dehydrogenase, both of which are exclusively mitochondrial enzymes, were below levels, shown by control tissue in every case, the average being 21.7% of the lowest control value for pyruvate carboxylase and 11.6% of that for pyruvate dehydrogenase. Impaired pyruvate metabolism appears to be another feature in Reye's syndrome.", "contents": "Deficient activity of hepatic pyruvate dehydrogenase and pyruvate carboxylase in Reye's syndrome. The activity of certain hepatic enzymes involved in carbohydrate metabolism was measured in postmortem samples from six cases of Reye's syndrome. The activities of the two exclusively extramitochondrial enzymes, glucose-6-phosphatase and fructose-1,6-diphosphatase, were all within the normal range. Activities of pyruvate carboxylase and pyruvate dehydrogenase, both of which are exclusively mitochondrial enzymes, were below levels, shown by control tissue in every case, the average being 21.7% of the lowest control value for pyruvate carboxylase and 11.6% of that for pyruvate dehydrogenase. Impaired pyruvate metabolism appears to be another feature in Reye's syndrome."}
{"id": "PMID:191790", "title": "The clinical, biochemical, and familial presentation of type V hyperlipoproteinemia in childhood.", "content": "Primary type V hyperlipoproteinemia was identified in two preadolescent children. The propositus (kindred N) was a 10-year-old girl with severely creamy plasma, lipemia retinalis, hypertriglyceridemia (triglyceridelevel, 6,800 mg/100 ml), and ypercholesterolemia (cholesterol level, 490 mg/100 ml). Her parents and an 8-year-old sister all had endogenous hypertriglyceridemia (type IV hyperlipoproteinemia). In kindred A, an 11-year-old boy had triglyceride levels as high as 1,100 mg/100 ml and recurrent abdominal pain. His father had type V hyperlipoproteinemia; his mother was normal. All three of his older teenage siblings had type IV hyperlipoproteinemia. The enzymatic activities of lipoprotein lipase (LPL), hepatic triglyceride lipase (HTL), and histaminase (H) were studied in postheparin plasma. The LPL level was low in the children and both parents in kindred N. LPL level in kindred A was normal, except for one child with type IV hyperlipoproteinemia. HTL level was normal to above normal in both kindreds. Most patients had a normal H level, but one parent (kindred N) had no preheparin H and very low levels of postheparin H. There was a strong correlation (r = 0.58, significant at less than 1% level) between release of LPL and H but not between HTL and H (r= 0.22). The mean (+/- 1 S.D.) levels of the enzymes were as follows: LPL, 2.8 +/- 0.7 micronmol/ml/hr in kindred N and 5.4 +/- 2.2 micronmol/ml/hr in kindred A; H, 13.4 +/- 6.8 units/ml in kindred N and 22.0 +/- 11.9 units/ml in kindred A; and HTL, 18.0 +/- 7.1 micronmol/ml/hr in kindred N and 14.9 +/- 6.3 micronmol/ml/hr in kindred A. The enzymatic activities of kindreds N and A were significantly different for LPL (P less than .001) and H (.025 less than P less than .05) but not for HTL. All but one child had at least one high insulin level, which was accompanied by hyperglycemia in two children. The hypertriglyceridemia in all but one child was ameliorated on therapeutic diets. These data suggest that the genetic basis of the hypertriglyceridemia in these two families is different and that hyperchylomicronemia in childhood is not confined to the rara type I hyperliporproteinemia.", "contents": "The clinical, biochemical, and familial presentation of type V hyperlipoproteinemia in childhood. Primary type V hyperlipoproteinemia was identified in two preadolescent children. The propositus (kindred N) was a 10-year-old girl with severely creamy plasma, lipemia retinalis, hypertriglyceridemia (triglyceridelevel, 6,800 mg/100 ml), and ypercholesterolemia (cholesterol level, 490 mg/100 ml). Her parents and an 8-year-old sister all had endogenous hypertriglyceridemia (type IV hyperlipoproteinemia). In kindred A, an 11-year-old boy had triglyceride levels as high as 1,100 mg/100 ml and recurrent abdominal pain. His father had type V hyperlipoproteinemia; his mother was normal. All three of his older teenage siblings had type IV hyperlipoproteinemia. The enzymatic activities of lipoprotein lipase (LPL), hepatic triglyceride lipase (HTL), and histaminase (H) were studied in postheparin plasma. The LPL level was low in the children and both parents in kindred N. LPL level in kindred A was normal, except for one child with type IV hyperlipoproteinemia. HTL level was normal to above normal in both kindreds. Most patients had a normal H level, but one parent (kindred N) had no preheparin H and very low levels of postheparin H. There was a strong correlation (r = 0.58, significant at less than 1% level) between release of LPL and H but not between HTL and H (r= 0.22). The mean (+/- 1 S.D.) levels of the enzymes were as follows: LPL, 2.8 +/- 0.7 micronmol/ml/hr in kindred N and 5.4 +/- 2.2 micronmol/ml/hr in kindred A; H, 13.4 +/- 6.8 units/ml in kindred N and 22.0 +/- 11.9 units/ml in kindred A; and HTL, 18.0 +/- 7.1 micronmol/ml/hr in kindred N and 14.9 +/- 6.3 micronmol/ml/hr in kindred A. The enzymatic activities of kindreds N and A were significantly different for LPL (P less than .001) and H (.025 less than P less than .05) but not for HTL. All but one child had at least one high insulin level, which was accompanied by hyperglycemia in two children. The hypertriglyceridemia in all but one child was ameliorated on therapeutic diets. These data suggest that the genetic basis of the hypertriglyceridemia in these two families is different and that hyperchylomicronemia in childhood is not confined to the rara type I hyperliporproteinemia."}
{"id": "PMID:191793", "title": "Effects of preloading of stannous compounds on the distribution of 99mTc-pertechnetate.", "content": "99MTc-pertechnetate distribution studies were performed in rabbits and mice following pretreatment between 5--336 hours with various routinely used stannous complexes (HSA, MAA, GHT, DTPA, PYPs) containing different amounts of Sn++ (0.17--15.0  mu mg/kg). Beyond a concentration of 0.26 mu mg/kg of Sn++ an alteration in 99mTc-ertechnetate distribution was observed. The red blood cell was found to be the most prominent target. An in-vivo reduction of 99mTc-pertechnetate apparently occurred by the presence of stannous ion within the red blood cell. Preloading time period between 5--24 hours did not alter the uptake of RBC/plasma ratio. Beyond that period it decreased slowly and still persisted up to 2 weeks following pretreatment. RBC/plasma ratio of 99mTcO4-increased with increased Sn++ content of various commercially available pharmaceutical kits.", "contents": "Effects of preloading of stannous compounds on the distribution of 99mTc-pertechnetate. 99MTc-pertechnetate distribution studies were performed in rabbits and mice following pretreatment between 5--336 hours with various routinely used stannous complexes (HSA, MAA, GHT, DTPA, PYPs) containing different amounts of Sn++ (0.17--15.0  mu mg/kg). Beyond a concentration of 0.26 mu mg/kg of Sn++ an alteration in 99mTc-ertechnetate distribution was observed. The red blood cell was found to be the most prominent target. An in-vivo reduction of 99mTc-pertechnetate apparently occurred by the presence of stannous ion within the red blood cell. Preloading time period between 5--24 hours did not alter the uptake of RBC/plasma ratio. Beyond that period it decreased slowly and still persisted up to 2 weeks following pretreatment. RBC/plasma ratio of 99mTcO4-increased with increased Sn++ content of various commercially available pharmaceutical kits."}
{"id": "PMID:191796", "title": "Teaching patients with peripheral vascular disease.", "content": "The teaching of a patient with peripheral vascular disease offers many challenges to the nurse. Although content should be understood and utilized by the patient and significant others, of primary importance is the belief that the learner is the curriculum and that his perception of self and his problems is the focus of teaching. The learning needs generally should be considered as the needs of an adult individual, who has many past experiences and an interest in the present and future. This patient may experience pain from his disease and may require the assistance and support of others. If the purpose of treatment is to improve circulation and prevent trauma and infection, then patient instruction must be recognized as a vital tool in therapy. But the nurse cognizant of the progressiveness of peripheral vascular disease must capitalized on the teachable moments--when the patient is ready and the learning is needed.", "contents": "Teaching patients with peripheral vascular disease. The teaching of a patient with peripheral vascular disease offers many challenges to the nurse. Although content should be understood and utilized by the patient and significant others, of primary importance is the belief that the learner is the curriculum and that his perception of self and his problems is the focus of teaching. The learning needs generally should be considered as the needs of an adult individual, who has many past experiences and an interest in the present and future. This patient may experience pain from his disease and may require the assistance and support of others. If the purpose of treatment is to improve circulation and prevent trauma and infection, then patient instruction must be recognized as a vital tool in therapy. But the nurse cognizant of the progressiveness of peripheral vascular disease must capitalized on the teachable moments--when the patient is ready and the learning is needed."}
{"id": "PMID:191800", "title": "Separation of subclasses of human serum high density lipoproteins by zonal ultracentrifugation.", "content": "An improved one-step method for the preparative separation of three subfractions of high-density lipoproteins from normal human serum has been developed. It employs the method of rate zonal ultracentrifugation in a z-60 rotor using a discontinuous NaBr gradient in the density range of 1.0-1.4. The density gradients were monitored directly by a flow-through density meter allowing the direct read-out of the actual densities in the process of filling and emptying the rotor. The separation of the three density fractions from 5 to 15 ml serum was achieved during a single 12 hours run at 59.000 rpm. The three fractions showed characteristically different patterns on polyacrylamide gel electrophoresis and differences in their lipid and protein composition.", "contents": "Separation of subclasses of human serum high density lipoproteins by zonal ultracentrifugation. An improved one-step method for the preparative separation of three subfractions of high-density lipoproteins from normal human serum has been developed. It employs the method of rate zonal ultracentrifugation in a z-60 rotor using a discontinuous NaBr gradient in the density range of 1.0-1.4. The density gradients were monitored directly by a flow-through density meter allowing the direct read-out of the actual densities in the process of filling and emptying the rotor. The separation of the three density fractions from 5 to 15 ml serum was achieved during a single 12 hours run at 59.000 rpm. The three fractions showed characteristically different patterns on polyacrylamide gel electrophoresis and differences in their lipid and protein composition."}
{"id": "PMID:191801", "title": "[Effect of cobamide coenzyme on the growth of several transplantable tumors in rats and on prolonging the life of rats with grafted Zajdel ascitic tumor].", "content": "The effect of the cobamide coenzyme (5,6-dimethylbenzimidazolyl-Co-5'-deoxyadenozylcobamide, DBC) on the growth of some forms of rat tumours and on the prolongation of survival of rats with implanted Zajdela ascites hepatoma was compared with that of cyanocobalamine (5,6-dimethylbenzimidazolyl-Co-cyanocobamide, CN-B12). The effect of DBC was shown to differ from that of CN-B12. DBC did not stimulate the growth of the investigated forms of tumours and prolonged survival of rats with implanted Zajdela ascites hepatoma. The rats displayed cancer resistance when DBC or CN-B12 were injected before implantation of tumours or Zajdela ascites hepatoma.", "contents": "[Effect of cobamide coenzyme on the growth of several transplantable tumors in rats and on prolonging the life of rats with grafted Zajdel ascitic tumor]. The effect of the cobamide coenzyme (5,6-dimethylbenzimidazolyl-Co-5'-deoxyadenozylcobamide, DBC) on the growth of some forms of rat tumours and on the prolongation of survival of rats with implanted Zajdela ascites hepatoma was compared with that of cyanocobalamine (5,6-dimethylbenzimidazolyl-Co-cyanocobamide, CN-B12). The effect of DBC was shown to differ from that of CN-B12. DBC did not stimulate the growth of the investigated forms of tumours and prolonged survival of rats with implanted Zajdela ascites hepatoma. The rats displayed cancer resistance when DBC or CN-B12 were injected before implantation of tumours or Zajdela ascites hepatoma."}
{"id": "PMID:191803", "title": "[Adrenocorticotropic function of the pituitary gland in endocrine diseases].", "content": "In examination of 123 patients with diabetes mellitus. Itsenko-Cushing disease, Addison's disease, thyrotoxicosis and adiposity there was revealed an increase in the content of the adrenocorticotropic hormone (ACTH) in the blood. Comparison of the ACTH and cortizol concentration in the blood permitted to suppose a different mechanism of the derangements revealed. An increase of the adrenocorticotropic function of the hypophysis in diabetes mellitus, Itsenko-Cushing disease and thyrotoxicosis was accompanied by a rise in the blood cortizol level. A fall of glucocorticoid function of the adrenal glands in Addison's disease and a relative hypocorticism in the patients with adiposity caused a compensatory intensification of the ACTH secretion.", "contents": "[Adrenocorticotropic function of the pituitary gland in endocrine diseases]. In examination of 123 patients with diabetes mellitus. Itsenko-Cushing disease, Addison's disease, thyrotoxicosis and adiposity there was revealed an increase in the content of the adrenocorticotropic hormone (ACTH) in the blood. Comparison of the ACTH and cortizol concentration in the blood permitted to suppose a different mechanism of the derangements revealed. An increase of the adrenocorticotropic function of the hypophysis in diabetes mellitus, Itsenko-Cushing disease and thyrotoxicosis was accompanied by a rise in the blood cortizol level. A fall of glucocorticoid function of the adrenal glands in Addison's disease and a relative hypocorticism in the patients with adiposity caused a compensatory intensification of the ACTH secretion."}
{"id": "PMID:191805", "title": "[Effect of long-term administration of hydrocortisone on the activity of glucosephosphatase and fructosediphosphatase and the synthesis of RNA fractions in the liver of rats of different age].", "content": "Experiments were conducted on albino rats of 3 age groups (2--3, 8--12, and 24--28-month-old). A study was made of the influence of prolonged administration of hydrocortisone on the activity of glucoso-6-phosphatase, fructoso-1,6-diphosphatase and the synthesis of RNA fractionated by the thermic phenol method. An increase of the enzyme activity, of the specific radioactivity, of the relative specific radioactivity of the RNA fractions was less pronounced in old rats. A comparatively early occurrence of the phenomenon of \"disruption\" of the inductive mechanisms of the hormonal stimulation was observed in the same age group.", "contents": "[Effect of long-term administration of hydrocortisone on the activity of glucosephosphatase and fructosediphosphatase and the synthesis of RNA fractions in the liver of rats of different age]. Experiments were conducted on albino rats of 3 age groups (2--3, 8--12, and 24--28-month-old). A study was made of the influence of prolonged administration of hydrocortisone on the activity of glucoso-6-phosphatase, fructoso-1,6-diphosphatase and the synthesis of RNA fractionated by the thermic phenol method. An increase of the enzyme activity, of the specific radioactivity, of the relative specific radioactivity of the RNA fractions was less pronounced in old rats. A comparatively early occurrence of the phenomenon of \"disruption\" of the inductive mechanisms of the hormonal stimulation was observed in the same age group."}
{"id": "PMID:191809", "title": "Cell-free translation of simian virus 40 early messenger RNA coding for viral T-antigen.", "content": "Simian virus 40 (SV40) mRNA was isolated by hybridization of cytoplasmic RNA, from SV40-infected BS-C-1 monkey cells early in lytic infection, to SV40 DNA immobilized on Sepharose. The early viral mRNA, when added to a wheat-germ translation system, directed the synthesis of a unique class of products including a 90,000 molecular weight (Mr) polypeptide. It was found that this 90,000 Mr product as well as a prominent 17,000 Mr polypeptide could be specifically immunoprecipitated with hamster antiserum to SV40 T-antigen, but not with hamster control serum. Similar immunoprecipitation of extracts of SV40-infected cells with hamster anti-T serum yielded 90,000 Mr and 17,000 Mr polypeptides; these polypeptides were not found in immunoprecipitates of uninfected cell extracts. SV40 cRNA, prepared by asymmetric transcription of plaque-purified SV40 DNA, directed the cell-free synthesis of several products, including a 70,000 Mr polypeptide that could be specifically immunoprecipitated with anti-T serum. However, no T-antigen-related polypeptide was found in infected cells that corresponded in size to the major immunoprecipitated cRNA product.", "contents": "Cell-free translation of simian virus 40 early messenger RNA coding for viral T-antigen. Simian virus 40 (SV40) mRNA was isolated by hybridization of cytoplasmic RNA, from SV40-infected BS-C-1 monkey cells early in lytic infection, to SV40 DNA immobilized on Sepharose. The early viral mRNA, when added to a wheat-germ translation system, directed the synthesis of a unique class of products including a 90,000 molecular weight (Mr) polypeptide. It was found that this 90,000 Mr product as well as a prominent 17,000 Mr polypeptide could be specifically immunoprecipitated with hamster antiserum to SV40 T-antigen, but not with hamster control serum. Similar immunoprecipitation of extracts of SV40-infected cells with hamster anti-T serum yielded 90,000 Mr and 17,000 Mr polypeptides; these polypeptides were not found in immunoprecipitates of uninfected cell extracts. SV40 cRNA, prepared by asymmetric transcription of plaque-purified SV40 DNA, directed the cell-free synthesis of several products, including a 70,000 Mr polypeptide that could be specifically immunoprecipitated with anti-T serum. However, no T-antigen-related polypeptide was found in infected cells that corresponded in size to the major immunoprecipitated cRNA product."}
{"id": "PMID:191810", "title": "Stoichiometry of GTP hydrolysis and tubulin polymerization.", "content": "Microtubule formation from lamb brain tubulin isolated by affinity chromatography and freed of exchangeable nucleotide requires GTP for maximal rate and extent of polymerization. The nucleotide analogs guanylylmethylenediphosphate and guanylylimidodiphosphate fail to replace GTP; in addition, neither the presence of microtubule associated proteins nor 5 M glycerol relieves the GTP requirement. The relation of GTP concentration and microtubule formation shows an association constant K = 1 X 10(4) M-1; furthermore, GDP and guanylylimidodiphosphate are competitive inhibitors of GTP for polymerization. Using a rapid filter assay for microtubule formation that allows the quantitative analysis of early polymerization kinetics and correcting for GTP hydrolysis uncoupled from tubulin polymerization, a stoichiometry of two molecules of GTP hydrolyzed per mole of tubulin dimer incorporated into microtubules has been found.", "contents": "Stoichiometry of GTP hydrolysis and tubulin polymerization. Microtubule formation from lamb brain tubulin isolated by affinity chromatography and freed of exchangeable nucleotide requires GTP for maximal rate and extent of polymerization. The nucleotide analogs guanylylmethylenediphosphate and guanylylimidodiphosphate fail to replace GTP; in addition, neither the presence of microtubule associated proteins nor 5 M glycerol relieves the GTP requirement. The relation of GTP concentration and microtubule formation shows an association constant K = 1 X 10(4) M-1; furthermore, GDP and guanylylimidodiphosphate are competitive inhibitors of GTP for polymerization. Using a rapid filter assay for microtubule formation that allows the quantitative analysis of early polymerization kinetics and correcting for GTP hydrolysis uncoupled from tubulin polymerization, a stoichiometry of two molecules of GTP hydrolyzed per mole of tubulin dimer incorporated into microtubules has been found."}
{"id": "PMID:191806", "title": "[Stimulating effect of human chorionic gonadotropin on the activity of guanidinoacetate-N-methyltransferase of rat testes: role of cyclic AMP].", "content": "A study was made of the influence of human chorionic gonadotropin (HCGT) on the activity of guanidineacetate-N-methyltranspherase in human testes. Guanidineacetate-methyltranspherase proved to be stimulated in the testes of the sexually immature rats in vivo under the action of HCGT on the 19th day after birth and from the 24th to the 27th day after birth. The activity of the enzyme was also increased in adult rats weighing 35--40 g. The activity of guanidineacetate-methyltranspherase in the testes of rats was particularly sharply stimulated after a single administration of N6-O2'-dibutiryladenosine-3',5'-cyclophosphate against the background of a preliminary treatment of rats with HCGT for a period of 5 days. The enzyme stimulation induced by combined treatment of rats with HCGT and N6-O2'-dibutiryladenosine-3',5'-cyclophosphate was prevented by the administration of cycloheximide and actinomycine D. The activity of the enzyme decreased after the incubation of the rat testes tissue homogenate with HCGT.", "contents": "[Stimulating effect of human chorionic gonadotropin on the activity of guanidinoacetate-N-methyltransferase of rat testes: role of cyclic AMP]. A study was made of the influence of human chorionic gonadotropin (HCGT) on the activity of guanidineacetate-N-methyltranspherase in human testes. Guanidineacetate-methyltranspherase proved to be stimulated in the testes of the sexually immature rats in vivo under the action of HCGT on the 19th day after birth and from the 24th to the 27th day after birth. The activity of the enzyme was also increased in adult rats weighing 35--40 g. The activity of guanidineacetate-methyltranspherase in the testes of rats was particularly sharply stimulated after a single administration of N6-O2'-dibutiryladenosine-3',5'-cyclophosphate against the background of a preliminary treatment of rats with HCGT for a period of 5 days. The enzyme stimulation induced by combined treatment of rats with HCGT and N6-O2'-dibutiryladenosine-3',5'-cyclophosphate was prevented by the administration of cycloheximide and actinomycine D. The activity of the enzyme decreased after the incubation of the rat testes tissue homogenate with HCGT."}
{"id": "PMID:191807", "title": "[Role of hormones of neurohypophysis in ACTH and glucocorticoid secretion].", "content": "The absence of a strict relationship between the antidiuretic activity of the posterior lobe of the hypophysis and the ACTH-glucocorticoid secretion was shown in experiments on rats. A conclusion was drawn that the neurohypophysial hormones played no significant role in the realization of the reaction of the hypophysioadrenal system to various actions, and could influence only the spontaneous level of the ACTH-glucocorticoid secretion.", "contents": "[Role of hormones of neurohypophysis in ACTH and glucocorticoid secretion]. The absence of a strict relationship between the antidiuretic activity of the posterior lobe of the hypophysis and the ACTH-glucocorticoid secretion was shown in experiments on rats. A conclusion was drawn that the neurohypophysial hormones played no significant role in the realization of the reaction of the hypophysioadrenal system to various actions, and could influence only the spontaneous level of the ACTH-glucocorticoid secretion."}
{"id": "PMID:191811", "title": "Heteroduplex analysis of avian RNA tumor viruses.", "content": "Electron microscopic heteroduplex analysis of avian RNA tumor viruses has been undertaken by using 35S viral RNA and long, complementary DNA synthesized in vitro. In this initial study, heteroduplex molecules were formed between complementary DNA from Rous sarcoma virus [Prague B strain (Pr-B)] and RNAs from Pr-B and Rous sarcoma virus [Prague C strain (Pr-C)] and from their transformation defective (td) derivatives, td-Pr-B and td-Pr-C. In the case of heteroduplexes with the td viruses, a deletion loop was observed of the order of two kilobases in size and less than one kilobase from the 3' terminus of the RNA. This deletion probably spans part or all of the sequences of one or more genes in the nondefective sarcoma virus which are essential for cell transformation. The sizes and the positions of the deletions in the td-Pr-B and td-Pr-C viruses were slightly, but significantly, different. No nonhomology features were observed in the Pr-B-Pr-C hybrids, thus confirming the close genetic relatedness of the two viruses. All heteroduplexes contained a proportion of circular and dimer molecules. This observation is a direct demonstration that (-) strand DNA transcription begins at an internal position of the RNA genome, proceeds to the 5' end, reinitiates at the 3' end of the RNA, and copies the remainder of the viral genome. Other implications for models of RNA tumor virus replication are also developed from these data.", "contents": "Heteroduplex analysis of avian RNA tumor viruses. Electron microscopic heteroduplex analysis of avian RNA tumor viruses has been undertaken by using 35S viral RNA and long, complementary DNA synthesized in vitro. In this initial study, heteroduplex molecules were formed between complementary DNA from Rous sarcoma virus [Prague B strain (Pr-B)] and RNAs from Pr-B and Rous sarcoma virus [Prague C strain (Pr-C)] and from their transformation defective (td) derivatives, td-Pr-B and td-Pr-C. In the case of heteroduplexes with the td viruses, a deletion loop was observed of the order of two kilobases in size and less than one kilobase from the 3' terminus of the RNA. This deletion probably spans part or all of the sequences of one or more genes in the nondefective sarcoma virus which are essential for cell transformation. The sizes and the positions of the deletions in the td-Pr-B and td-Pr-C viruses were slightly, but significantly, different. No nonhomology features were observed in the Pr-B-Pr-C hybrids, thus confirming the close genetic relatedness of the two viruses. All heteroduplexes contained a proportion of circular and dimer molecules. This observation is a direct demonstration that (-) strand DNA transcription begins at an internal position of the RNA genome, proceeds to the 5' end, reinitiates at the 3' end of the RNA, and copies the remainder of the viral genome. Other implications for models of RNA tumor virus replication are also developed from these data."}
{"id": "PMID:191804", "title": "[Age-specific characteristics of the effect of various hormones on the lipolysis in the adipose tissue of rats under normal conditions and in starvation].", "content": "Experiments were conducted in vitro; a study was mode of the age peculiarities attending be invluence of adrenaline, ACTH, STH on the lypolysis in the adipose tissue of rats under normal conditions and in starvation. During the process of ageing there occurs no change in the adipose tissue sensitivity to the action of hormones stimulating the lipolysis, but the capacity to react to high hormone doses is decreased. Elevation of the basal lypolysis in the adipose tissue of young rats occurs during starvation; the lypolytic action of the hormones falls. Starvation fails to alter the basal lypolysis in the adipose tissue to react to the hormone action.", "contents": "[Age-specific characteristics of the effect of various hormones on the lipolysis in the adipose tissue of rats under normal conditions and in starvation]. Experiments were conducted in vitro; a study was mode of the age peculiarities attending be invluence of adrenaline, ACTH, STH on the lypolysis in the adipose tissue of rats under normal conditions and in starvation. During the process of ageing there occurs no change in the adipose tissue sensitivity to the action of hormones stimulating the lipolysis, but the capacity to react to high hormone doses is decreased. Elevation of the basal lypolysis in the adipose tissue of young rats occurs during starvation; the lypolytic action of the hormones falls. Starvation fails to alter the basal lypolysis in the adipose tissue to react to the hormone action."}
{"id": "PMID:191812", "title": "Mapping of transcription sites of simian virus 40-specific late 16S and 19S mRNA by electron microscopy.", "content": "Simian virus 40 (SV40) late 19S and 16S mRNAs were annealed to complementary regions of partially melted viral double-stranded SV40(LHpa II) DNA or SV40(LBam HI) DNA. The RNA-DNA hybrid regions within the DNA molecules were visualized as loops [with SV40(LBam HI) DNA] in the electron microscope. The data confirm the previous localizations of the 3' and 5' ends of 16S SV40 mRNA and of the 3' end of late 19S SV40 mRNA. The 5' end of the major stable SV40 late 19S mRNA has been positioned at 0.755 map unit. Thus, the sequences of viral DNA from 0.655 to 0.755 map unit, including the replication origin, are not converted into major stable species of late viral mRNA.", "contents": "Mapping of transcription sites of simian virus 40-specific late 16S and 19S mRNA by electron microscopy. Simian virus 40 (SV40) late 19S and 16S mRNAs were annealed to complementary regions of partially melted viral double-stranded SV40(LHpa II) DNA or SV40(LBam HI) DNA. The RNA-DNA hybrid regions within the DNA molecules were visualized as loops [with SV40(LBam HI) DNA] in the electron microscope. The data confirm the previous localizations of the 3' and 5' ends of 16S SV40 mRNA and of the 3' end of late 19S SV40 mRNA. The 5' end of the major stable SV40 late 19S mRNA has been positioned at 0.755 map unit. Thus, the sequences of viral DNA from 0.655 to 0.755 map unit, including the replication origin, are not converted into major stable species of late viral mRNA."}
{"id": "PMID:191813", "title": "Bovine papilloma virus: presence of virus-specific DNA sequences in naturally occurring equine tumors.", "content": "Four of five spontaneous benign equine connective tissue tumors of unknown etiology and a bovine papilloma virus (BPV)-induced equine tumor contained BPV-specific DNA sequences as determined by DNA-DNA hybridization of DNA from tumors with BPV DNA labeled in vitro. Analysis of the kinetics of reassociation indicated that 20-75% of the BPV genome was present in the various tumors. The number of partial BPV genome equivalents ranged from 60 to 500 copies per diploid quantity of cellular DNA. Thermal denaturation profiles of duplexes formed between labeled BPV DNA and DNA from tumor cells indicated two tumors contained viral DNA with base sequences identical to BPV DNA. Three tumors (including DNA from the BPV-induced tumor) contained BPV-related DNA sequences that were less thermally stable. The decrease in thermal denaturation temperature may be due to the presence of (adenine + thymine)-rich regions of the BPV genome in the tumor cells.", "contents": "Bovine papilloma virus: presence of virus-specific DNA sequences in naturally occurring equine tumors. Four of five spontaneous benign equine connective tissue tumors of unknown etiology and a bovine papilloma virus (BPV)-induced equine tumor contained BPV-specific DNA sequences as determined by DNA-DNA hybridization of DNA from tumors with BPV DNA labeled in vitro. Analysis of the kinetics of reassociation indicated that 20-75% of the BPV genome was present in the various tumors. The number of partial BPV genome equivalents ranged from 60 to 500 copies per diploid quantity of cellular DNA. Thermal denaturation profiles of duplexes formed between labeled BPV DNA and DNA from tumor cells indicated two tumors contained viral DNA with base sequences identical to BPV DNA. Three tumors (including DNA from the BPV-induced tumor) contained BPV-related DNA sequences that were less thermally stable. The decrease in thermal denaturation temperature may be due to the presence of (adenine + thymine)-rich regions of the BPV genome in the tumor cells."}
{"id": "PMID:191814", "title": "Specific changes in the pattern of protein synthesis during meiotic maturation of mammalian oocytes in vitro.", "content": "High resolution two-dimensional electrophoresis has been used to examine the pattern of protein synthesis during meiotic maturation of mouse oocytes in vitro. Fluorograms of [35S]methionine-labeled oocyte proteins have revealed that meiotic progression from dictyate to metaphase II (meiotic maturation) is accompanied by marked changes in the pattern of proteins synthesized by oocytes. Virtually all of the changes observed take place subsequent to the breakdown of the oocyte's germinal vesicle, but are not dependent upon the occurrence of other morphological events, such as spindle formation or polar body emission. These changes in protein synthesis do not take place in oocytes that fail to undergo breakdown of germinal vesicles spontaneously or in oocytes arrested at the germinal vesicle stage by dibutyryl 3':5'-cyclic AMP. These data suggest that mixing of the oocyte's nucleoplasm and cytoplasm may trigger many of the changes in protein synthesis that accompany meiotic maturation of mouse oocytes in vitro.", "contents": "Specific changes in the pattern of protein synthesis during meiotic maturation of mammalian oocytes in vitro. High resolution two-dimensional electrophoresis has been used to examine the pattern of protein synthesis during meiotic maturation of mouse oocytes in vitro. Fluorograms of [35S]methionine-labeled oocyte proteins have revealed that meiotic progression from dictyate to metaphase II (meiotic maturation) is accompanied by marked changes in the pattern of proteins synthesized by oocytes. Virtually all of the changes observed take place subsequent to the breakdown of the oocyte's germinal vesicle, but are not dependent upon the occurrence of other morphological events, such as spindle formation or polar body emission. These changes in protein synthesis do not take place in oocytes that fail to undergo breakdown of germinal vesicles spontaneously or in oocytes arrested at the germinal vesicle stage by dibutyryl 3':5'-cyclic AMP. These data suggest that mixing of the oocyte's nucleoplasm and cytoplasm may trigger many of the changes in protein synthesis that accompany meiotic maturation of mouse oocytes in vitro."}
{"id": "PMID:191815", "title": "Surface localization of sites of reduction of nitroxide spin-labeled molecules in mitochondria.", "content": "The relative rates of reduction of several spin-labeled molecules that partition differently across the hy-drophobic-interface of inner membranes from rat liver mitochondria were investigated. Spin labels localized either deep in the hydrophobic region or in the aqueous phase are only slowly reduced; however a spin-labeled analogue of the cationic detergent cetyltrimethylammonium bromide that partitions at the interface is rapidly reduced by coupled electron transport. Chemical studies on the reduction and oxidation of the spin label show that loss of signal is due to reduction and not destruction of the label. No evidence was found for flip-flop of the label in submitochondrial preparations. Spin reduction of respiring mitochondria, mitoplasts, or inverted submitochondrial preparations is inhibited by rotenone but is relatively insensitive to antimycin A and KCN. Because the midpoint potentials of the spin labels were found to be similar to that of ubiquinone, it is concluded that reducing equivalents of mitochondrial electron transport from this region of the chain are channeled to either membrane interface.", "contents": "Surface localization of sites of reduction of nitroxide spin-labeled molecules in mitochondria. The relative rates of reduction of several spin-labeled molecules that partition differently across the hy-drophobic-interface of inner membranes from rat liver mitochondria were investigated. Spin labels localized either deep in the hydrophobic region or in the aqueous phase are only slowly reduced; however a spin-labeled analogue of the cationic detergent cetyltrimethylammonium bromide that partitions at the interface is rapidly reduced by coupled electron transport. Chemical studies on the reduction and oxidation of the spin label show that loss of signal is due to reduction and not destruction of the label. No evidence was found for flip-flop of the label in submitochondrial preparations. Spin reduction of respiring mitochondria, mitoplasts, or inverted submitochondrial preparations is inhibited by rotenone but is relatively insensitive to antimycin A and KCN. Because the midpoint potentials of the spin labels were found to be similar to that of ubiquinone, it is concluded that reducing equivalents of mitochondrial electron transport from this region of the chain are channeled to either membrane interface."}
{"id": "PMID:191816", "title": "Gonadotropin-induced regulation of luteinizing hormone receptors and desensitization of testicular 3':5'-cyclic AMP and testosterone responses.", "content": "Administration of human chorionic gonadotropin (hCG) to male rats was followed by dose-related changes in luteinizing hormone (LH) receptors in the testis. After treatment with a low dose of hCG (10international units), the number of LH receptors increased slightly over the first 24 hr, then fell to about 30% of the control value. These changes occurred with occupancy of only 8% of the available receptors, and were initially accompanied by increased basal testosterone production in vitro with no change in basal 3'5'-cyclic AMP production. During stimulation with hCG in vitro, such testes showed a transient decrease in cyclic AMP response on the first day after gonadotropin treatment and no change in testosterone response. By contrast, a 20-fold higher dose of hCG caused more rapid and complete loss of LH receptors, with major and transient occupancy of receptors at 24 hr and marked elevations of basal cyclic AMP and testosterone production in vitro. The initial occupancy of receptors was accompanied by a rapid fall in the cyclic AMP response to hCG in vitro, and was followed by marked receptor loss and inhibition of the cyclic AMP response for up to 5 days. The testosterone response to hCG in vitro was completely inhibited for about 3 days, then rose to the control level at 5 days, when only a small proportion of the original receptor sites and cyclic AMP response had begun to return. Such complete recovery of the steroidogenic response when only a fraction of the receptor population had returned was consistent with the presence of receptor reserve or \"spare\" receptors in the testis. These studies have demonstrated that negative regulation of LH receptors by exogenous gonadotropin is accompanied by consequent changes in cyclic AMP and testosterone responses to hCG in vitro. Hormone induced desensitization of interstitial cell responses was initially related to occupancy of LH receptors and later to a protracted loss of receptor sites.", "contents": "Gonadotropin-induced regulation of luteinizing hormone receptors and desensitization of testicular 3':5'-cyclic AMP and testosterone responses. Administration of human chorionic gonadotropin (hCG) to male rats was followed by dose-related changes in luteinizing hormone (LH) receptors in the testis. After treatment with a low dose of hCG (10international units), the number of LH receptors increased slightly over the first 24 hr, then fell to about 30% of the control value. These changes occurred with occupancy of only 8% of the available receptors, and were initially accompanied by increased basal testosterone production in vitro with no change in basal 3'5'-cyclic AMP production. During stimulation with hCG in vitro, such testes showed a transient decrease in cyclic AMP response on the first day after gonadotropin treatment and no change in testosterone response. By contrast, a 20-fold higher dose of hCG caused more rapid and complete loss of LH receptors, with major and transient occupancy of receptors at 24 hr and marked elevations of basal cyclic AMP and testosterone production in vitro. The initial occupancy of receptors was accompanied by a rapid fall in the cyclic AMP response to hCG in vitro, and was followed by marked receptor loss and inhibition of the cyclic AMP response for up to 5 days. The testosterone response to hCG in vitro was completely inhibited for about 3 days, then rose to the control level at 5 days, when only a small proportion of the original receptor sites and cyclic AMP response had begun to return. Such complete recovery of the steroidogenic response when only a fraction of the receptor population had returned was consistent with the presence of receptor reserve or \"spare\" receptors in the testis. These studies have demonstrated that negative regulation of LH receptors by exogenous gonadotropin is accompanied by consequent changes in cyclic AMP and testosterone responses to hCG in vitro. Hormone induced desensitization of interstitial cell responses was initially related to occupancy of LH receptors and later to a protracted loss of receptor sites."}
{"id": "PMID:191817", "title": "Binding and internalization of thrombin by normal and transformed chick cells.", "content": "Thrombin stimulates cell proliferation in cultures of normal chick embryo fibroblasts but not in cells transformed with Rous sarcoma virus. Analysis of medium conditioned by Rous-sarcoma-virus-transformed cultures demonstrates that these cells do not secrete molecules that can inhibit or inactivate thrombin. The interaction of thrombin with these cells was investigated with enzymatically active 125I-thrombin. The amount of cell-associated 125I-thrombin was found to be three times greater with normal cells than with transformed cells. In both types of cell, greater than 50% of the total cell-associated 125I-thrombin was found as a component that was not dissociated from the cells by trypsin treatment, an observation suggesting that a significant portion was not on the cell surface. The amount of the trypsin-insensitive fraction increases with time up to 12 hr, whereas the trypsin-sensitive fraction is saturated after 1-4 hr. Autoradiography of thin sections of 125I-thrombin-treated cells observed by electron microscopy reveals that after 10 hr incubation greater than 70% of the label is localized in the cytoplasm of both normal and transformed cells. Autoradiograms of sodium dodecyl sulfate/polyacrylamide slab gels demonstrate that 40% of the intracellular label is the size of native thrombin with the remainder in two large fragments of 22,000 and 19,500 daltons.", "contents": "Binding and internalization of thrombin by normal and transformed chick cells. Thrombin stimulates cell proliferation in cultures of normal chick embryo fibroblasts but not in cells transformed with Rous sarcoma virus. Analysis of medium conditioned by Rous-sarcoma-virus-transformed cultures demonstrates that these cells do not secrete molecules that can inhibit or inactivate thrombin. The interaction of thrombin with these cells was investigated with enzymatically active 125I-thrombin. The amount of cell-associated 125I-thrombin was found to be three times greater with normal cells than with transformed cells. In both types of cell, greater than 50% of the total cell-associated 125I-thrombin was found as a component that was not dissociated from the cells by trypsin treatment, an observation suggesting that a significant portion was not on the cell surface. The amount of the trypsin-insensitive fraction increases with time up to 12 hr, whereas the trypsin-sensitive fraction is saturated after 1-4 hr. Autoradiography of thin sections of 125I-thrombin-treated cells observed by electron microscopy reveals that after 10 hr incubation greater than 70% of the label is localized in the cytoplasm of both normal and transformed cells. Autoradiograms of sodium dodecyl sulfate/polyacrylamide slab gels demonstrate that 40% of the intracellular label is the size of native thrombin with the remainder in two large fragments of 22,000 and 19,500 daltons."}
{"id": "PMID:191818", "title": "The number of receptors for beta-melanocyte stimulating hormone in Cloudman melanoma cells is increased by dibutyryl adenosine 3':5'-cyclic monophosphate or cholera toxin.", "content": "Cultured Cloudman melanoma cells exposed either to dibutyryl 3':5'-cyclic AMP and theophylline or to cholera toxin bind significantly more 125I-labeled beta-melanocyte stimulating hormone (MSH) and fluorescein-labeled MSH than untreated cells. MSH binds to melanoma cells in the G2 phase of the cell cycle. The stimulation of MSH binding by dibutyryl cyclic AMP results from an increase in the number of MSH receptors per G2 cell and, to a lesser extent, from an increase in the number of G2 cells. The affinity of the receptors for MSH is not influenced by dibutyryl cyclic AMP.", "contents": "The number of receptors for beta-melanocyte stimulating hormone in Cloudman melanoma cells is increased by dibutyryl adenosine 3':5'-cyclic monophosphate or cholera toxin. Cultured Cloudman melanoma cells exposed either to dibutyryl 3':5'-cyclic AMP and theophylline or to cholera toxin bind significantly more 125I-labeled beta-melanocyte stimulating hormone (MSH) and fluorescein-labeled MSH than untreated cells. MSH binds to melanoma cells in the G2 phase of the cell cycle. The stimulation of MSH binding by dibutyryl cyclic AMP results from an increase in the number of MSH receptors per G2 cell and, to a lesser extent, from an increase in the number of G2 cells. The affinity of the receptors for MSH is not influenced by dibutyryl cyclic AMP."}
{"id": "PMID:191819", "title": "A transplantable insulinoma in the rat.", "content": "A transplantable insulinoma was developed in inbred albino rats of the NEDH strain. The original tumor, 1 cm in diameter, was removed from the pancreas of a male parabiont 566 days folowing 1000 rads (10J/kg) of total body x-irradiation. The time required for implanted fragments to grow to 0.5-1.5 cm in diameter decreased from 5-8 months in the first generation to 2-5 months in the seventh generation. Successful transplantation in male animals followed for 4 or more months after transplantation was significantly greater than in female animals followed for a similar period of time (96% versus 69%). Light and electron microscopy revealed that the tumors consisted predominantly of well-granulated beta cells. Ultrastructural studies also showed small numbers of D-cells. Tumor extracts contained an average of 223 units of immunoreactive insulin and 25.9 mug of immunoreactive somato-statin per gram wet weight of tissue. Tumors generally produced increasingly profound hypoglycemia within 2-4 months following transplantation, with plasma glucose levels frequently falling to 40 mg/100 ml or lower prior to death. Removal of tumors from chronically hypoglycemic animals resulted in transient rebound hyperglycemia with plasma glucose levels above 300mg/100 ml within the first 24 hr and a gradual decline to normal levels of 129 mg/100ml in 2-4 days. These observations correlated with findings of marked atropy and degranulation of the beta cells in the pancreata of tumor-bearing animals, and with gradual return of normal light microscopic morphology following tumor removal.", "contents": "A transplantable insulinoma in the rat. A transplantable insulinoma was developed in inbred albino rats of the NEDH strain. The original tumor, 1 cm in diameter, was removed from the pancreas of a male parabiont 566 days folowing 1000 rads (10J/kg) of total body x-irradiation. The time required for implanted fragments to grow to 0.5-1.5 cm in diameter decreased from 5-8 months in the first generation to 2-5 months in the seventh generation. Successful transplantation in male animals followed for 4 or more months after transplantation was significantly greater than in female animals followed for a similar period of time (96% versus 69%). Light and electron microscopy revealed that the tumors consisted predominantly of well-granulated beta cells. Ultrastructural studies also showed small numbers of D-cells. Tumor extracts contained an average of 223 units of immunoreactive insulin and 25.9 mug of immunoreactive somato-statin per gram wet weight of tissue. Tumors generally produced increasingly profound hypoglycemia within 2-4 months following transplantation, with plasma glucose levels frequently falling to 40 mg/100 ml or lower prior to death. Removal of tumors from chronically hypoglycemic animals resulted in transient rebound hyperglycemia with plasma glucose levels above 300mg/100 ml within the first 24 hr and a gradual decline to normal levels of 129 mg/100ml in 2-4 days. These observations correlated with findings of marked atropy and degranulation of the beta cells in the pancreata of tumor-bearing animals, and with gradual return of normal light microscopic morphology following tumor removal."}
{"id": "PMID:191820", "title": "Presence of corticotropin in brain of normal and hypophysectomized rats.", "content": "Immunoreactive and bioreactive corticotropin (ACTH-like) activities have been detected in the median eminence and remaining medial basal hypothalamus of both normal and hypophysectomized adult male rats: bioreactive ACTH (pg/100 mug of protein) 1028 in median eminence and 1289 in medial basal hypothalamus; immunoreactive ACTH (midportion ACTH antibody), 1554 in median eminence and 1887 in medial basal hypothalamus. By use of appropriate antibodies and bioassay, it was demonstrated that immunoreactivity was not due solely to alpha-melanotropin, which has previously been reported to be present in the brain of hypophysectomized animals. The Sephadex G-50 gel filtration patterns determined by immunoassay of column eluates obtained from hypothalamic extracts of normal or hypophysectomized animals were similar but were not identical to the pattern derived from whole pituitary. Immunoreactive (midportion ACTH antibody) ACTH concentrations (pg/100 mug of protein) of other central nervous system areas in normal animals were: cerebellum 34.3, cortex 46.3, thalamus 23.8, and hippocampus 116.3. The total amount of bioreactive ACTH present in the median eminence and medial basal hypothalamus is approximately 1% of that present in the pituitary. The present data suggest that such ACTH may have a diencephalic rather than pituitary origin and raise the question of the functional significance of such ACTH.", "contents": "Presence of corticotropin in brain of normal and hypophysectomized rats. Immunoreactive and bioreactive corticotropin (ACTH-like) activities have been detected in the median eminence and remaining medial basal hypothalamus of both normal and hypophysectomized adult male rats: bioreactive ACTH (pg/100 mug of protein) 1028 in median eminence and 1289 in medial basal hypothalamus; immunoreactive ACTH (midportion ACTH antibody), 1554 in median eminence and 1887 in medial basal hypothalamus. By use of appropriate antibodies and bioassay, it was demonstrated that immunoreactivity was not due solely to alpha-melanotropin, which has previously been reported to be present in the brain of hypophysectomized animals. The Sephadex G-50 gel filtration patterns determined by immunoassay of column eluates obtained from hypothalamic extracts of normal or hypophysectomized animals were similar but were not identical to the pattern derived from whole pituitary. Immunoreactive (midportion ACTH antibody) ACTH concentrations (pg/100 mug of protein) of other central nervous system areas in normal animals were: cerebellum 34.3, cortex 46.3, thalamus 23.8, and hippocampus 116.3. The total amount of bioreactive ACTH present in the median eminence and medial basal hypothalamus is approximately 1% of that present in the pituitary. The present data suggest that such ACTH may have a diencephalic rather than pituitary origin and raise the question of the functional significance of such ACTH."}
{"id": "PMID:191821", "title": "Dissociation of increases in levels of 3':5'-cyclic AMP and 3':5'-cyclic GMP from induction of ornithine decarboxylase by the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate in mouse epidermis in vivo.", "content": "A single application of 17 nmol of 12-O-tetradecanoyl phorbol-13-acetate (TPA) to mouse skin caused a marked (200- to 400-fold) induction of ornithine decarboxylase (EC 4.1.1.17, L-ornithine carboxy-lyase) activity in mouse epidermal and epidermal-dermal preparations. No change in the basal level of 3':5'-cyclic AMP occurred in epidermal-dermal preparations within 30 min of TPA application. Intraperitoneal injection of the beta-agonist isoproterenol resulted in a dose-dependent accumulation of 3':5'-cyclic AMP occurred in epidermal-dermal preparations within 30 min of TPA application. Intraperitoneal injection of the beta-agonist isoproterenol resulted in a dose-dependent accumulation of 3':5'-cyclic AMP 10 min after injection, but caused no induction of ornithine decarboxylase. When isoproterenol was injected 10 min prior to an application of either 1.7 or 17 nmol of TPA, the magnitude of the ornithine decarboxylase induction was the same as induction with TPA alone. Topical application of 17 nmol of TPA caused no increase in the level of 3':5'-cyclic GMP present in the mouse epidermal-dermal preparations 2-20 min after application. Intraperitoneal injection of 1.75 mumol of dibutyryl 3':5'-cyclic GMP and/or butyryl derivatives of cyclic GMP caused a 6-fold increase in the level of cyclic GMP and/or butyryl derivatives of cyclic GMP in epidermal-dermal preparations within 5 min of injection, and the level remained elevated for at least 20-30 min. This dose of dibutyryl 3':5'-cyclic GMP was incapable of inducing ornithine decarboxylase. Injection of dibutyryl 3':5'-cyclic GMP 5 min before application of 1.7 nmol of TPA or 30 min before application of 17 nmol of TPA did not alter the magnitude of the ornithine decarboxylase induction produced by TPA alone. These results suggest that early increases in the total intracellular levels of either 3':5'-cyclic AMP or 3':5'-cyclic GMP are not part of the mechanism by which TPA induces ornithine decarboxylase in the epidermis.", "contents": "Dissociation of increases in levels of 3':5'-cyclic AMP and 3':5'-cyclic GMP from induction of ornithine decarboxylase by the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate in mouse epidermis in vivo. A single application of 17 nmol of 12-O-tetradecanoyl phorbol-13-acetate (TPA) to mouse skin caused a marked (200- to 400-fold) induction of ornithine decarboxylase (EC 4.1.1.17, L-ornithine carboxy-lyase) activity in mouse epidermal and epidermal-dermal preparations. No change in the basal level of 3':5'-cyclic AMP occurred in epidermal-dermal preparations within 30 min of TPA application. Intraperitoneal injection of the beta-agonist isoproterenol resulted in a dose-dependent accumulation of 3':5'-cyclic AMP occurred in epidermal-dermal preparations within 30 min of TPA application. Intraperitoneal injection of the beta-agonist isoproterenol resulted in a dose-dependent accumulation of 3':5'-cyclic AMP 10 min after injection, but caused no induction of ornithine decarboxylase. When isoproterenol was injected 10 min prior to an application of either 1.7 or 17 nmol of TPA, the magnitude of the ornithine decarboxylase induction was the same as induction with TPA alone. Topical application of 17 nmol of TPA caused no increase in the level of 3':5'-cyclic GMP present in the mouse epidermal-dermal preparations 2-20 min after application. Intraperitoneal injection of 1.75 mumol of dibutyryl 3':5'-cyclic GMP and/or butyryl derivatives of cyclic GMP caused a 6-fold increase in the level of cyclic GMP and/or butyryl derivatives of cyclic GMP in epidermal-dermal preparations within 5 min of injection, and the level remained elevated for at least 20-30 min. This dose of dibutyryl 3':5'-cyclic GMP was incapable of inducing ornithine decarboxylase. Injection of dibutyryl 3':5'-cyclic GMP 5 min before application of 1.7 nmol of TPA or 30 min before application of 17 nmol of TPA did not alter the magnitude of the ornithine decarboxylase induction produced by TPA alone. These results suggest that early increases in the total intracellular levels of either 3':5'-cyclic AMP or 3':5'-cyclic GMP are not part of the mechanism by which TPA induces ornithine decarboxylase in the epidermis."}
{"id": "PMID:191822", "title": "Role of surface modulating assemblies in growth control of normal and transformed fibroblasts.", "content": "Cellular microtubules, microfilaments, and surface receptors have been postulated to form a surface modulating assembly that regulates surface receptor mobility and cell growth. To test this hypothesis, we examined three agents known to affect cell growth [colchicine, concanavalin A (Con A), and the src gene product of Rous sarcoma virus] for their effects on chick embryo fibroblasts. Individual cells from serum-starved normal fibroblast populations became committed to enter S phase at various times over a 12 hr period after exposure to serum. Colchicine and other microtubule-disrupting agents blocked entry into S phase at a point close to the commitment point for each cell. The lectin Con A also blocked entry into the S phase when present in doses sufficient to modulate surface receptor mobility. In contrast, succinyl-Con A, which does not induce surface modulation, had no effect. Both Con A and colchicine blocked the appearance of cytoplasmic factors capable of stimulating DNA replication in a cell-free system. To study endogenous effects on the surface modulating assembly, we infected fibroblasts with a Rous sarcoma virus (tsNY68) having a temperature-sensitive mutation in the transforming (src) gene. We have previously shown that microtubular and microfilamentous structures of the surface modulating assembly are direct or indirect targets of the src gene product with consequent reduction in the capacity of Con A to induce surface modulation. TsNY68-infected fibroblasts shifted to the non-permissive temperature acquired normal microtubular morphology more rapidly (2 hr) than cells grown at the permissive temperature in the presence of protein synthesis inhibitors (7.5 hr). This suggests that the src gene product acts directly on the surface modulating assembly rather than via the nucleus or at the level of protein synthesis. Furthermore, \"transformation\" of the surface modulating assembly was partly blocked by treatment of the infected cells with Con A but not succinyl-Con A. Both Con A and colchicine inhibited entry into the S phase following a shift from nonpermissive to permissive growth conditions. All of these observations are in accord with the hypothesis that the surface modulating assembly acts as a signal regulator in growth control.", "contents": "Role of surface modulating assemblies in growth control of normal and transformed fibroblasts. Cellular microtubules, microfilaments, and surface receptors have been postulated to form a surface modulating assembly that regulates surface receptor mobility and cell growth. To test this hypothesis, we examined three agents known to affect cell growth [colchicine, concanavalin A (Con A), and the src gene product of Rous sarcoma virus] for their effects on chick embryo fibroblasts. Individual cells from serum-starved normal fibroblast populations became committed to enter S phase at various times over a 12 hr period after exposure to serum. Colchicine and other microtubule-disrupting agents blocked entry into S phase at a point close to the commitment point for each cell. The lectin Con A also blocked entry into the S phase when present in doses sufficient to modulate surface receptor mobility. In contrast, succinyl-Con A, which does not induce surface modulation, had no effect. Both Con A and colchicine blocked the appearance of cytoplasmic factors capable of stimulating DNA replication in a cell-free system. To study endogenous effects on the surface modulating assembly, we infected fibroblasts with a Rous sarcoma virus (tsNY68) having a temperature-sensitive mutation in the transforming (src) gene. We have previously shown that microtubular and microfilamentous structures of the surface modulating assembly are direct or indirect targets of the src gene product with consequent reduction in the capacity of Con A to induce surface modulation. TsNY68-infected fibroblasts shifted to the non-permissive temperature acquired normal microtubular morphology more rapidly (2 hr) than cells grown at the permissive temperature in the presence of protein synthesis inhibitors (7.5 hr). This suggests that the src gene product acts directly on the surface modulating assembly rather than via the nucleus or at the level of protein synthesis. Furthermore, \"transformation\" of the surface modulating assembly was partly blocked by treatment of the infected cells with Con A but not succinyl-Con A. Both Con A and colchicine inhibited entry into the S phase following a shift from nonpermissive to permissive growth conditions. All of these observations are in accord with the hypothesis that the surface modulating assembly acts as a signal regulator in growth control."}
{"id": "PMID:191823", "title": "Mutagenesis in S49 mouse lymphoma cells: induction of resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP.", "content": "The effects of mutagens on three genetic markers--resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP (Bt2cAMP), were investigated in a mouse lymphoma cell line, S49. Nitrosoguanidine, ethyl methanesulfonate, ICR 191, and x-rays were used. Mutagen-specific responses were seen. Ouabain resistance was induced by nitrosoguanidine, but not by ICR 191. ICR 191 induced resistance to 6-thioguanine more efficiently than did nitrosoguanidine; the converse was true of resistance to Bt2cAMP. The relative frequency of biochemically distinguishable subtypes of mutants resistant to Bt2cAMP was characteristic of the mutagen used to generate them. The results can be interpreted as follows: nitrosoguanidine and ethyl methanesulfonate frequently, but ICR 191 and x-rays rarely, give rise to DNA base sequence changes that result in structurally altered but functional proteins. This type of change is required for induction of mutants resistant to ouabain and of certain classes of mutants resistant to Bt2cAMP. Resistance to 6-thioguanine and other classes of mutants resistant to Bt2cAMP can result from DNA base sequence changes that lead to extensive alteration of protein structure or expression; these changes are induced by ICR 191 or x-rays.", "contents": "Mutagenesis in S49 mouse lymphoma cells: induction of resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP. The effects of mutagens on three genetic markers--resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP (Bt2cAMP), were investigated in a mouse lymphoma cell line, S49. Nitrosoguanidine, ethyl methanesulfonate, ICR 191, and x-rays were used. Mutagen-specific responses were seen. Ouabain resistance was induced by nitrosoguanidine, but not by ICR 191. ICR 191 induced resistance to 6-thioguanine more efficiently than did nitrosoguanidine; the converse was true of resistance to Bt2cAMP. The relative frequency of biochemically distinguishable subtypes of mutants resistant to Bt2cAMP was characteristic of the mutagen used to generate them. The results can be interpreted as follows: nitrosoguanidine and ethyl methanesulfonate frequently, but ICR 191 and x-rays rarely, give rise to DNA base sequence changes that result in structurally altered but functional proteins. This type of change is required for induction of mutants resistant to ouabain and of certain classes of mutants resistant to Bt2cAMP. Resistance to 6-thioguanine and other classes of mutants resistant to Bt2cAMP can result from DNA base sequence changes that lead to extensive alteration of protein structure or expression; these changes are induced by ICR 191 or x-rays."}
{"id": "PMID:191824", "title": "Host-determined differences in expression of surface marker characteristics on human and simian lymphoblastoid cell lines transformed by Epstein-Barr virus.", "content": "In an attempt to account for differences in the biologic behavior of Epstein-Barr virus in different primate species, we studied lymphocyte surface markers on primary and transformed cells. Among primary leukocytes, the distribution of cells with characteristics of bone-marrow-derived cells (B cells) was similar in humans, wooly monkeys, and cotton-top marmosets. However, after transformation by Epstein-Barr virus, cells from each species were characterically different. Transformed human umbilical cord cells expressed the complement receptor; monkey cells exhibited both this receptor and the receptor for IgG Fc (EA7S); and marmoset cells did not have either surface marker. We measured the transformation efficiency of human and marmoset leukocyte subpopulations enriched or depeleted in cells with the complement receptor. In both species the highest efficiencies of transformation were found in populations with the greatest numbers of cells with the receptor. The data therefore suggest that, in all species, a cell with the complement receptor is susceptible to transformation but that this receptor is not expressed on transformed marmoset cells. Thus, in Epstein-Barr virus-induced transformation it is necessary to distinguish between transformation of growth properties (immortalization) and transformation of cell surface properties.", "contents": "Host-determined differences in expression of surface marker characteristics on human and simian lymphoblastoid cell lines transformed by Epstein-Barr virus. In an attempt to account for differences in the biologic behavior of Epstein-Barr virus in different primate species, we studied lymphocyte surface markers on primary and transformed cells. Among primary leukocytes, the distribution of cells with characteristics of bone-marrow-derived cells (B cells) was similar in humans, wooly monkeys, and cotton-top marmosets. However, after transformation by Epstein-Barr virus, cells from each species were characterically different. Transformed human umbilical cord cells expressed the complement receptor; monkey cells exhibited both this receptor and the receptor for IgG Fc (EA7S); and marmoset cells did not have either surface marker. We measured the transformation efficiency of human and marmoset leukocyte subpopulations enriched or depeleted in cells with the complement receptor. In both species the highest efficiencies of transformation were found in populations with the greatest numbers of cells with the receptor. The data therefore suggest that, in all species, a cell with the complement receptor is susceptible to transformation but that this receptor is not expressed on transformed marmoset cells. Thus, in Epstein-Barr virus-induced transformation it is necessary to distinguish between transformation of growth properties (immortalization) and transformation of cell surface properties."}
{"id": "PMID:191825", "title": "Reduction of collagen biosynthesis in blood vessels and other tissues by reserpine and hypophysectomy.", "content": "Synthesis of collagen in the vasculature and other tissues of normotensive rats is markedly reduced by reserpine. Hypophysectomy produces similar effects. The effects of reserpine on collagen biosynthesis may be mediated through the hypothalamus.", "contents": "Reduction of collagen biosynthesis in blood vessels and other tissues by reserpine and hypophysectomy. Synthesis of collagen in the vasculature and other tissues of normotensive rats is markedly reduced by reserpine. Hypophysectomy produces similar effects. The effects of reserpine on collagen biosynthesis may be mediated through the hypothalamus."}
{"id": "PMID:191826", "title": "A new class of murine leukemia virus associated with development of spontaneous lymphomas.", "content": "A new type of murine leukemia virus has been detected in thymuses of leukemic and late preleukemic AKR mice, in lymphomas developing in NIH Swiss mice carrying the AKR ectopic virus-inducing loci Akv-I or Akv-2, and in the thymus of a preleukemic C58 mouse. The viruses induce focal areas of morphologic alteration in a mink lung cell line and are tentatively referred to as \"mink cell focus-inducing\" (MCF) strains. They have the host range of both xenotropic and N-tropic ecotropic murine leukemia viruses, are neutralized by antisera to both ecotropic and xenotropic viruses, and are interfered with by both viruses. They may represent a particular type of genetic recombinant which emerges during the preleukemic period in high-ecotropic-virus mouse strains, and they may play a significant role in the etiology of spontaneous lymphomas.", "contents": "A new class of murine leukemia virus associated with development of spontaneous lymphomas. A new type of murine leukemia virus has been detected in thymuses of leukemic and late preleukemic AKR mice, in lymphomas developing in NIH Swiss mice carrying the AKR ectopic virus-inducing loci Akv-I or Akv-2, and in the thymus of a preleukemic C58 mouse. The viruses induce focal areas of morphologic alteration in a mink lung cell line and are tentatively referred to as \"mink cell focus-inducing\" (MCF) strains. They have the host range of both xenotropic and N-tropic ecotropic murine leukemia viruses, are neutralized by antisera to both ecotropic and xenotropic viruses, and are interfered with by both viruses. They may represent a particular type of genetic recombinant which emerges during the preleukemic period in high-ecotropic-virus mouse strains, and they may play a significant role in the etiology of spontaneous lymphomas."}
{"id": "PMID:191827", "title": "Structure of human plasma low-density lipoproteins: molecular organization of the central core.", "content": "Human plasma low density lipoprotein (LDL) exhibits a thermal transition over the temperature range 20-40 degrees. This transition is associated with a structural change within the lipoprotein particle and is reflected in the small-angle x-ray scattering profiles from LDL. The scattering profile of the quasispherical LDL particle at 10 degrees shows a relatively intense maximum at 1/36 A-1 which is absent from the scattering of LDL at 45 degrees. Theoretical calculations, using model electron density distributions, have been carried out to describe the packing of arrangement of the cholesterol esters, based on perturbations of the molecular packing of crystalline cholesteryl myristate, adequately reproduces the high relative intensity of the x-ray scattering maximum at 1/36 A-1. The perturbations of the packing in the crystal structure of cholesteryl myristate involve \"melting\" of the hydrocarbon chains of the esters together with translations of pairs of molecules parallel to the molecular long axis. The interaction of opposing steroid moieties, with C18 and C19 angular methyl groups interlocked, exhibited in the crystal structure is retained in the perturbed arrangement. At 45 degrees, thermally induced disorder of this arrangement averages the electron density of the central core. The x-ray scattering profiles of particles with a homogeneous electron density in the core region do not show a high relative intensity of the subsidiary maxima in the 1/36 A-1 region, in agreement with experimental observation. The results of these calculations support the concept that the thermal transition observed for LDL is due to a smectic leads to disordered transition of the cholesterol esters in the core of the LDL particle.", "contents": "Structure of human plasma low-density lipoproteins: molecular organization of the central core. Human plasma low density lipoprotein (LDL) exhibits a thermal transition over the temperature range 20-40 degrees. This transition is associated with a structural change within the lipoprotein particle and is reflected in the small-angle x-ray scattering profiles from LDL. The scattering profile of the quasispherical LDL particle at 10 degrees shows a relatively intense maximum at 1/36 A-1 which is absent from the scattering of LDL at 45 degrees. Theoretical calculations, using model electron density distributions, have been carried out to describe the packing of arrangement of the cholesterol esters, based on perturbations of the molecular packing of crystalline cholesteryl myristate, adequately reproduces the high relative intensity of the x-ray scattering maximum at 1/36 A-1. The perturbations of the packing in the crystal structure of cholesteryl myristate involve \"melting\" of the hydrocarbon chains of the esters together with translations of pairs of molecules parallel to the molecular long axis. The interaction of opposing steroid moieties, with C18 and C19 angular methyl groups interlocked, exhibited in the crystal structure is retained in the perturbed arrangement. At 45 degrees, thermally induced disorder of this arrangement averages the electron density of the central core. The x-ray scattering profiles of particles with a homogeneous electron density in the core region do not show a high relative intensity of the subsidiary maxima in the 1/36 A-1 region, in agreement with experimental observation. The results of these calculations support the concept that the thermal transition observed for LDL is due to a smectic leads to disordered transition of the cholesterol esters in the core of the LDL particle."}
{"id": "PMID:191828", "title": "Cell-surface glycosyltransferases in cultured fibroblasts: increased activity and release during serum stimulation of growth.", "content": "Cell-surface galactosyltransferase was studied in suspensions of intact baby hamster kidney fibroblasts with both endogenous and exogenous glycoprotein acceptors. The cell-surface location of galactosyltransferase was demonstrated in experiments with the enzyme modifier alpha-lactalbumin, which does not enter the cell. The addition of alpha-lactalbumin to the assay medium for galactosyltransferase resulted in accumulation of lactose in the medium but not in the cells. There was no detectable hydrolysis of UDP-galactose to free galactose by these cells, nor did a 100-fold molar excess of free galactose inhibit cell-surface galactosyltransferase. There was a marked increase in specific activity of cell-surface exogenous galactosyltransferase in serum-stimulated as compared to resting fibroblasts. Dividing but not resting fibroblasts released galactosyltransferase, but not sialyl- or fucosyltransferase, in soluble form into the tissue culture medium. The release of galactosyltransferase was greater from virally transformed than from nontransformed fibroblasts.", "contents": "Cell-surface glycosyltransferases in cultured fibroblasts: increased activity and release during serum stimulation of growth. Cell-surface galactosyltransferase was studied in suspensions of intact baby hamster kidney fibroblasts with both endogenous and exogenous glycoprotein acceptors. The cell-surface location of galactosyltransferase was demonstrated in experiments with the enzyme modifier alpha-lactalbumin, which does not enter the cell. The addition of alpha-lactalbumin to the assay medium for galactosyltransferase resulted in accumulation of lactose in the medium but not in the cells. There was no detectable hydrolysis of UDP-galactose to free galactose by these cells, nor did a 100-fold molar excess of free galactose inhibit cell-surface galactosyltransferase. There was a marked increase in specific activity of cell-surface exogenous galactosyltransferase in serum-stimulated as compared to resting fibroblasts. Dividing but not resting fibroblasts released galactosyltransferase, but not sialyl- or fucosyltransferase, in soluble form into the tissue culture medium. The release of galactosyltransferase was greater from virally transformed than from nontransformed fibroblasts."}
{"id": "PMID:191829", "title": "Incorporation of N-acetylglucosamine into endogenous acceptors of rough microsomes from rat liver: stimulation by GTP after treatment with pyrophosphate.", "content": "Upon incubation of UDP-N-acetyl[14C]glucosamine and GDP-mannose with rough microsomes from rat liver, GlcNAc incorporation occurred mostly into acid-labile products extractable by chloroform/methanol that were presumed to be dolichol pyrophosphate GlcNAc and, for a small part, dolichol pyrophosphate N,N'-diacetylchitobiose. The production of this latter glycolipid was greatly enhanced when rough microsomes, previously treated with pyrophosphate, were incubated in the presence of GTP. Furthermore, under these particular conditions, high levels of radioactivity were obtained in products precipitated by trichloroacetic acid and not extracted by chloroform/methanol. The label appeared in acid-labile and in acid-resistant products, presumed to be dolichol pyrophosphate mannosylated oligosaccharides, and glycoproteins, respectively. From these results, dolichol pyrophosphate N,N'-diacetylchitobiose appears to be an obligate metabolic intermediate in protein glycosylation by this system. Whether or not dolichol pyrophosphate N,N'-diacetylchitobiose must be mannosylated prior to transfer of the N,N'-diacetylchitobiose moiety to protein is an open matter, because GlcNAc was also incorporated into acid-resistant products when the reaction was carried out in absence of GDP-mannose.", "contents": "Incorporation of N-acetylglucosamine into endogenous acceptors of rough microsomes from rat liver: stimulation by GTP after treatment with pyrophosphate. Upon incubation of UDP-N-acetyl[14C]glucosamine and GDP-mannose with rough microsomes from rat liver, GlcNAc incorporation occurred mostly into acid-labile products extractable by chloroform/methanol that were presumed to be dolichol pyrophosphate GlcNAc and, for a small part, dolichol pyrophosphate N,N'-diacetylchitobiose. The production of this latter glycolipid was greatly enhanced when rough microsomes, previously treated with pyrophosphate, were incubated in the presence of GTP. Furthermore, under these particular conditions, high levels of radioactivity were obtained in products precipitated by trichloroacetic acid and not extracted by chloroform/methanol. The label appeared in acid-labile and in acid-resistant products, presumed to be dolichol pyrophosphate mannosylated oligosaccharides, and glycoproteins, respectively. From these results, dolichol pyrophosphate N,N'-diacetylchitobiose appears to be an obligate metabolic intermediate in protein glycosylation by this system. Whether or not dolichol pyrophosphate N,N'-diacetylchitobiose must be mannosylated prior to transfer of the N,N'-diacetylchitobiose moiety to protein is an open matter, because GlcNAc was also incorporated into acid-resistant products when the reaction was carried out in absence of GDP-mannose."}
{"id": "PMID:191830", "title": "Tumorigenicity of simian virus 40-transformed human cells and mouse--human hybrids in nude mice.", "content": "Four different human cell lines transformed by simian virus 40 (SV40) were tested for their tumorigenicity in athymic nude mice. Two of these lines, W18Va2 and GM52VA, were found to be tumorigenic when inoculated at a concentration of 1 x 10(7) cells per mouse. The other two cell lines, LN-SV and GM54VA, were found to induce very small tumors only after the injection of approximately 1 x 10(8) cells per mouse. Somatic cell hybrids between either LN-SV or GM54VA SV40-transformed human cells and normal mouse peritoneal macrophages, which have retained the human chromosomes carrying the SV40 genome, were found to be much more tumorigenic than the SV40-transformed human cell parents. These experiments suggest that the genetic background in which the human chromosomes carrying the SV40 genome are present plays a role in the modulation of the expiration of malignancy.", "contents": "Tumorigenicity of simian virus 40-transformed human cells and mouse--human hybrids in nude mice. Four different human cell lines transformed by simian virus 40 (SV40) were tested for their tumorigenicity in athymic nude mice. Two of these lines, W18Va2 and GM52VA, were found to be tumorigenic when inoculated at a concentration of 1 x 10(7) cells per mouse. The other two cell lines, LN-SV and GM54VA, were found to induce very small tumors only after the injection of approximately 1 x 10(8) cells per mouse. Somatic cell hybrids between either LN-SV or GM54VA SV40-transformed human cells and normal mouse peritoneal macrophages, which have retained the human chromosomes carrying the SV40 genome, were found to be much more tumorigenic than the SV40-transformed human cell parents. These experiments suggest that the genetic background in which the human chromosomes carrying the SV40 genome are present plays a role in the modulation of the expiration of malignancy."}
{"id": "PMID:191831", "title": "Subunit interaction in cyclic AMP-dependent protein kinase of mutant lymphoma cells.", "content": "We have previously selected and characterized mutant S49 mouse lymphoma cells that possess an adenosine 3':5'-cyclic monophosphate (cAMP)-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) with an increased apparent affinity constant (Ka) for activation by cAMP. The Ka lesion in one such mutant clone has been shown to result from a structural mutation involving the kinase holoenzyme's regulatory (R) subunit. The present report examines the interaction of R and catalytic (C) subunits of the kinases in extracts of the mutant cells and the normal \"wild type\" (WT) parental line. Subunit recombination experiments were performed, by using purified WT and mutant R subunits, and C subunits purified from WT cells. As compared to WT R subunits, only 1/6 as much mutant R subunit was required to reassociate with and suppress 50% of C subunit activity, at equilibrium. NaSCN activates cAMP-dependent kinase of both cell types by causing the holoenzyme to dissociate. In comparison with WT, a 2-fold higher concentration of NaSCN is required to maximally activate the kinase in mutant extracts. Both the reassociation result and the increased resistance of the mutant enzyme to a nonspecific dissociating agent strongly suggest that the mutant R subunit binds C subunit more tightly than does the WT R subunit. This interpretation raises the possibility that increased R-C subunit binding affinity in the mutant cell is responsible for the increased Ka for activation by cAMP of the mutant holoenzyme, and thus for the decreased potency of cAMP in regulating intact mutant cells.", "contents": "Subunit interaction in cyclic AMP-dependent protein kinase of mutant lymphoma cells. We have previously selected and characterized mutant S49 mouse lymphoma cells that possess an adenosine 3':5'-cyclic monophosphate (cAMP)-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) with an increased apparent affinity constant (Ka) for activation by cAMP. The Ka lesion in one such mutant clone has been shown to result from a structural mutation involving the kinase holoenzyme's regulatory (R) subunit. The present report examines the interaction of R and catalytic (C) subunits of the kinases in extracts of the mutant cells and the normal \"wild type\" (WT) parental line. Subunit recombination experiments were performed, by using purified WT and mutant R subunits, and C subunits purified from WT cells. As compared to WT R subunits, only 1/6 as much mutant R subunit was required to reassociate with and suppress 50% of C subunit activity, at equilibrium. NaSCN activates cAMP-dependent kinase of both cell types by causing the holoenzyme to dissociate. In comparison with WT, a 2-fold higher concentration of NaSCN is required to maximally activate the kinase in mutant extracts. Both the reassociation result and the increased resistance of the mutant enzyme to a nonspecific dissociating agent strongly suggest that the mutant R subunit binds C subunit more tightly than does the WT R subunit. This interpretation raises the possibility that increased R-C subunit binding affinity in the mutant cell is responsible for the increased Ka for activation by cAMP of the mutant holoenzyme, and thus for the decreased potency of cAMP in regulating intact mutant cells."}
{"id": "PMID:191832", "title": "Feline oncornavirus-associated cell-membrane antigen (FOCMA): distinction between FOCMA and the major virion glycoprotein.", "content": "The humoral antibody response of feline leukemia virus (FeLV)-exposed cats to the feline oncornavirus-associated tumor cell-membrane antigen (FOCMA) is directly correlated with immunosurveillance against tumor development under natural conditions. By means of membrane immunofluorescence and radioimmunoprecipitation, the antibody response to FOCMA was found to be independent of the antibody response to the major envelope and core proteins of FeLV, gp70 and p30. This was especially true for healthy viremic cats, where antigenemia with circulating FeLV gp70 and p30 apparently binds any free antibody to these proteins, but high levels of FOCMA antibody are often concurrently present. Exhaustive in vitro absorption of highly immune nonviremic serum with gp70 and p30 also failed to remove FOCMA antibody activity. These results indicate that FOCMA is not one of these major FeLV structural proteins.", "contents": "Feline oncornavirus-associated cell-membrane antigen (FOCMA): distinction between FOCMA and the major virion glycoprotein. The humoral antibody response of feline leukemia virus (FeLV)-exposed cats to the feline oncornavirus-associated tumor cell-membrane antigen (FOCMA) is directly correlated with immunosurveillance against tumor development under natural conditions. By means of membrane immunofluorescence and radioimmunoprecipitation, the antibody response to FOCMA was found to be independent of the antibody response to the major envelope and core proteins of FeLV, gp70 and p30. This was especially true for healthy viremic cats, where antigenemia with circulating FeLV gp70 and p30 apparently binds any free antibody to these proteins, but high levels of FOCMA antibody are often concurrently present. Exhaustive in vitro absorption of highly immune nonviremic serum with gp70 and p30 also failed to remove FOCMA antibody activity. These results indicate that FOCMA is not one of these major FeLV structural proteins."}
{"id": "PMID:191833", "title": "Natural human antibodies reactive with primate type-C viral antigens.", "content": "A survey of human sera from healthy individuals revealed the presence of naturally occurring antibodies that react in radioimmunoprecipitation assays with proteins of mammalian type-C viruses. Of 39 sera tested, 100% showed reactivity against baboon endogenous virus, whereas only 49% showed reactivity against simian sarcoma-associated virus. Polyacrylamide gel electrophoresis of immune precipitates revealed one to three bands that comigrate with the virus structural proteins. There were low, but detectable, levels of antibody to the major internal protein of murine leukemia virus, but no activity against the structural proteins of avian sarcoma virus.", "contents": "Natural human antibodies reactive with primate type-C viral antigens. A survey of human sera from healthy individuals revealed the presence of naturally occurring antibodies that react in radioimmunoprecipitation assays with proteins of mammalian type-C viruses. Of 39 sera tested, 100% showed reactivity against baboon endogenous virus, whereas only 49% showed reactivity against simian sarcoma-associated virus. Polyacrylamide gel electrophoresis of immune precipitates revealed one to three bands that comigrate with the virus structural proteins. There were low, but detectable, levels of antibody to the major internal protein of murine leukemia virus, but no activity against the structural proteins of avian sarcoma virus."}
{"id": "PMID:191834", "title": "Characterization of polyoma virus T antigen.", "content": "High-titer antiserum raised in rats against the tumor (T) antigen of polyoma virus was used to purify the T antigen by the Staphylococcus protein A antibody adsorbent technique. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis allowed the identification of a protein with an apparent molecular weight of 100,000-108,000 as a major component induced in lytically infected mouse cells. In cells infected by ts A mutants this component was temperature sensitive. Several minor components were also observed. In pulse and chase experiments there was a slight decrease in electrophoretic mobility of T antigen during the chase period at the permissive temperature, suggesting that the T antigen is a modified protein. In two lines of transformed cells, the amount of T antigen seemed to be considerably less than in lytically infected cells, but the size of the antigen appeared to be equal.", "contents": "Characterization of polyoma virus T antigen. High-titer antiserum raised in rats against the tumor (T) antigen of polyoma virus was used to purify the T antigen by the Staphylococcus protein A antibody adsorbent technique. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis allowed the identification of a protein with an apparent molecular weight of 100,000-108,000 as a major component induced in lytically infected mouse cells. In cells infected by ts A mutants this component was temperature sensitive. Several minor components were also observed. In pulse and chase experiments there was a slight decrease in electrophoretic mobility of T antigen during the chase period at the permissive temperature, suggesting that the T antigen is a modified protein. In two lines of transformed cells, the amount of T antigen seemed to be considerably less than in lytically infected cells, but the size of the antigen appeared to be equal."}
{"id": "PMID:191835", "title": "Structure of a large segment of the genome of simian virus 40 that does not encode known proteins.", "content": "The nucleotide sequence of the region of DNA of simian virus 40 extending from 0.595 to 0.790 map unit has been derived. The sequence includes the DNA complementary to the 5' end of early mRNA and to the 5' end of some of the forms of late RNA. Because there are termination codons in all three phases in early and late RNA, there is a sequence of almost 800 nucleotides of simian virus 40 DNA that probably does not code for known viral proteins. The sequence spans the 5' end of the early mRNA at 0.67 map unit and overlaps a species of late RNA whose 5' end is at 0.65 map unit and whose 3' end is at 0.77 map unit. This RNA is retained on oligo(dT)-cellulose columns in high salt concentrations. Analysis of the sequence of late strand RNA suggests that this RNA is not covalently linked to the mRNA that encodes structural proteins. There is another species of late RNA of simian virus 40 whose 5' end is at 0.775 map unit. The nucleotide sequence of this region of simian virus 40 DNA contains several examples of repeated sequences, most of which are located in DNA that does not encode known peptides. These may be analogous to the reiterated sequences that have been described in animal cell DNA.", "contents": "Structure of a large segment of the genome of simian virus 40 that does not encode known proteins. The nucleotide sequence of the region of DNA of simian virus 40 extending from 0.595 to 0.790 map unit has been derived. The sequence includes the DNA complementary to the 5' end of early mRNA and to the 5' end of some of the forms of late RNA. Because there are termination codons in all three phases in early and late RNA, there is a sequence of almost 800 nucleotides of simian virus 40 DNA that probably does not code for known viral proteins. The sequence spans the 5' end of the early mRNA at 0.67 map unit and overlaps a species of late RNA whose 5' end is at 0.65 map unit and whose 3' end is at 0.77 map unit. This RNA is retained on oligo(dT)-cellulose columns in high salt concentrations. Analysis of the sequence of late strand RNA suggests that this RNA is not covalently linked to the mRNA that encodes structural proteins. There is another species of late RNA of simian virus 40 whose 5' end is at 0.775 map unit. The nucleotide sequence of this region of simian virus 40 DNA contains several examples of repeated sequences, most of which are located in DNA that does not encode known peptides. These may be analogous to the reiterated sequences that have been described in animal cell DNA."}
{"id": "PMID:191836", "title": "Mapping of closed circular DNAs  by cleavage with restriction endonucleases and calibration by agarose gel electrophoresis.", "content": "The cleavage of DNA by restriction endonucleases can be limited by the addition of ethidium bromide. When closed circular DNA is used as a substrate, DNA with one-site cleavages of one or both strands can be made by adding appropriate amounts of dye. The singly cleaved DNA is a complete set of full-length permuted linear molecules. Fractionation of the products of a digestion of the permuted linears with a single-hitting restriction endonuclease by gel electrophoresis yields a series of bands that can be used to determine relative molecular weights of the DNA fragments in the gel without the introduction of standards. It is possible to determine the relative molecular weight of a fragment to within +/-2.5%. These molecular weights immediately allow the determination of the HindIII and Hpa I maps of simian virus 40. The HindIII map of bacteriophage PM2 was determined by this method with one ambiguity that was resolved by using traditional techniques.", "contents": "Mapping of closed circular DNAs  by cleavage with restriction endonucleases and calibration by agarose gel electrophoresis. The cleavage of DNA by restriction endonucleases can be limited by the addition of ethidium bromide. When closed circular DNA is used as a substrate, DNA with one-site cleavages of one or both strands can be made by adding appropriate amounts of dye. The singly cleaved DNA is a complete set of full-length permuted linear molecules. Fractionation of the products of a digestion of the permuted linears with a single-hitting restriction endonuclease by gel electrophoresis yields a series of bands that can be used to determine relative molecular weights of the DNA fragments in the gel without the introduction of standards. It is possible to determine the relative molecular weight of a fragment to within +/-2.5%. These molecular weights immediately allow the determination of the HindIII and Hpa I maps of simian virus 40. The HindIII map of bacteriophage PM2 was determined by this method with one ambiguity that was resolved by using traditional techniques."}
{"id": "PMID:191837", "title": "Induction of functional beta-adrenergic receptors in HeLa cells.", "content": "HeLa cells contain beta-adrenergic receptors that are characterized by specific binding of I[3H]dihydroalprenolol, increased 3':5'-cyclic AMP production in intact cells after incubation with l-isoproterenol, and increased adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in the presence of l-isoproterenol. After cells were cultured with butyrate, the number of beta-adrenergic receptors, cyclic AMP production in intact cells, and adenylate cyclase activation by l-isoproterenol were increased severalfold over those of untreated cells. The increase involved the induction of synthesis of new receptor molecules with identical affinities for l-[3H]-dihydroalprenolol; all three processes were blocked by cycloheximide and actinomycin D. This induction was relatively specific for butyric acid and only the closely related short-chain fatty acids, propionic and valeric acids, were capable of partially inducing the same effect. In contrast to induction of beta-adrenergic binding sites, there was no increase in basal or fluoride-activated adenylate cyclase activity, indicating that the beta-adrenergic receptor and adenylate cyclase and different molecules that may be controlled separately.", "contents": "Induction of functional beta-adrenergic receptors in HeLa cells. HeLa cells contain beta-adrenergic receptors that are characterized by specific binding of I[3H]dihydroalprenolol, increased 3':5'-cyclic AMP production in intact cells after incubation with l-isoproterenol, and increased adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in the presence of l-isoproterenol. After cells were cultured with butyrate, the number of beta-adrenergic receptors, cyclic AMP production in intact cells, and adenylate cyclase activation by l-isoproterenol were increased severalfold over those of untreated cells. The increase involved the induction of synthesis of new receptor molecules with identical affinities for l-[3H]-dihydroalprenolol; all three processes were blocked by cycloheximide and actinomycin D. This induction was relatively specific for butyric acid and only the closely related short-chain fatty acids, propionic and valeric acids, were capable of partially inducing the same effect. In contrast to induction of beta-adrenergic binding sites, there was no increase in basal or fluoride-activated adenylate cyclase activity, indicating that the beta-adrenergic receptor and adenylate cyclase and different molecules that may be controlled separately."}
{"id": "PMID:191838", "title": "Histaminase (diamine oxidase) activity in human tumors: an expression of a mature genome.", "content": "High histaminase [amine:oxygen oxidoreductase (deaminating) (pyridoxal-containing), EC 1.4.3.6] activity is found in certain human tumors and in the placenta of most mammals. The present study explores the relationship of tumor histaminase to histaminases found in placenta and other human, pig, and rat tissues. The electrophoretic mobility and Michaelis constants for the deamination of histimine and putrescine were identical for histaminases from human placenta and from medullary thyroid carcinoma. An antibody was raised in rabbits against human placental histaminase that was highly purified by a new affinity procedure. In separate studies, using inhibitory concentrations of antibody and a second antibody precipitation technique, identical patterns of immunoreactivity were found for histaminases from human placenta, kidney, medullary thyroid carcinoma, and small cell lung carcinoma; human intestinal histaminase crossreacted well but less strongly than did enzymes from these other tissues. Histaminases from pig kidney, pig intestine, and rat intestine showed no crossreaction; histaminases from rat thymus and adrenal gland showed minimal crossreactivity. The findings suggest that placental histaminase activity is not a unique product of a fetal or trophoblastic genome. The presence of histaminase in malignancies does not appear to be an example of ectopic tumor production of a placental trophoblastic protein.", "contents": "Histaminase (diamine oxidase) activity in human tumors: an expression of a mature genome. High histaminase [amine:oxygen oxidoreductase (deaminating) (pyridoxal-containing), EC 1.4.3.6] activity is found in certain human tumors and in the placenta of most mammals. The present study explores the relationship of tumor histaminase to histaminases found in placenta and other human, pig, and rat tissues. The electrophoretic mobility and Michaelis constants for the deamination of histimine and putrescine were identical for histaminases from human placenta and from medullary thyroid carcinoma. An antibody was raised in rabbits against human placental histaminase that was highly purified by a new affinity procedure. In separate studies, using inhibitory concentrations of antibody and a second antibody precipitation technique, identical patterns of immunoreactivity were found for histaminases from human placenta, kidney, medullary thyroid carcinoma, and small cell lung carcinoma; human intestinal histaminase crossreacted well but less strongly than did enzymes from these other tissues. Histaminases from pig kidney, pig intestine, and rat intestine showed no crossreaction; histaminases from rat thymus and adrenal gland showed minimal crossreactivity. The findings suggest that placental histaminase activity is not a unique product of a fetal or trophoblastic genome. The presence of histaminase in malignancies does not appear to be an example of ectopic tumor production of a placental trophoblastic protein."}
{"id": "PMID:191839", "title": "Granulocyte collagenase: selective digestion of type I relative to type III collagen.", "content": "Collagenases produced by human polymorphonuclear leukocytes, human lung fibroblasts, and rabbit pulmonary alveolar macrophages were compared in their ability to digest soluble native type I and type III collagens. While the fibroblast and macrophage collagenases attacked the two substrates at approximately equal rates, the leukocyte collagenase attacked type I collagen preferentially (15:1) in comparison to type III collagen. This was true with human or rabbit collagen substrates. Thus, proteolysis of collagen, particularly in acute inflammation, may have a significant role in controlling the types of collagen present in connective tissue.", "contents": "Granulocyte collagenase: selective digestion of type I relative to type III collagen. Collagenases produced by human polymorphonuclear leukocytes, human lung fibroblasts, and rabbit pulmonary alveolar macrophages were compared in their ability to digest soluble native type I and type III collagens. While the fibroblast and macrophage collagenases attacked the two substrates at approximately equal rates, the leukocyte collagenase attacked type I collagen preferentially (15:1) in comparison to type III collagen. This was true with human or rabbit collagen substrates. Thus, proteolysis of collagen, particularly in acute inflammation, may have a significant role in controlling the types of collagen present in connective tissue."}
{"id": "PMID:191840", "title": "Cleavage of Rous sarcoma viral polypeptide precursor into internal structural proteins in vitro involves viral protein p15.", "content": "The polypeptide precursor pr76 to the internal viral group specific (gs) antigen proteins of Rous sarcoma virus, synthesized in a cell-free system of ascites cells, has been processed in vitro into the viral proteins by purified viral protein p15 as well as by disrupted Rous sarcoma virus. Disrupted Rauscher murine leukemia virus does not stimulate the cleavage process in vitro. Autocatalytic cleavage of the polypeptide precursor pr76 or Rous sarcoma virus, which contains the peptide sequence of p15, is not observed.", "contents": "Cleavage of Rous sarcoma viral polypeptide precursor into internal structural proteins in vitro involves viral protein p15. The polypeptide precursor pr76 to the internal viral group specific (gs) antigen proteins of Rous sarcoma virus, synthesized in a cell-free system of ascites cells, has been processed in vitro into the viral proteins by purified viral protein p15 as well as by disrupted Rous sarcoma virus. Disrupted Rauscher murine leukemia virus does not stimulate the cleavage process in vitro. Autocatalytic cleavage of the polypeptide precursor pr76 or Rous sarcoma virus, which contains the peptide sequence of p15, is not observed."}
{"id": "PMID:191841", "title": "Covalent linkage of a protein to a defined nucleotide sequence at the 5'-terminus of virion and replicative intermediate RNAs of poliovirus.", "content": "The 5'-terminus of poliovirus polyribosomal RNA is pUp. A candidate for the 5'-terminus of poliovirion RNA was recovered as a compound migrating toward the cathode when 32P-labeled virion RNA was completely digested with ribonucleases T1, T2 and A and analyzed by paper ionophoresis at pH 3.5. Treatment with proteinase K reversed its direction of migration, indicating the presence of protein. Treatment with venom phosphodiesterase liberated all of the radioactivity as pUp, suggesting that poliovirion RNA has a protein-pUp 5'-terminus. Treatment of virion RNA with T1 ribonuclease alone generated a proteinase K-sensitive oligoribonucleotide. Analysis of the oligoribonucleotide using ribonucleases A and U2 showed its structure to be protein-pU-U-A-A-A-A-C-A-G. Digests of replicative intermediate RNA contained sufficient protein-pUp to suggest that this structure is at the 5'-end of most nascent poliovirus RNA molecules. We suggest that a protein-nucleotide structure acts as a primer for initiating synthesis of poliovirus RNA.", "contents": "Covalent linkage of a protein to a defined nucleotide sequence at the 5'-terminus of virion and replicative intermediate RNAs of poliovirus. The 5'-terminus of poliovirus polyribosomal RNA is pUp. A candidate for the 5'-terminus of poliovirion RNA was recovered as a compound migrating toward the cathode when 32P-labeled virion RNA was completely digested with ribonucleases T1, T2 and A and analyzed by paper ionophoresis at pH 3.5. Treatment with proteinase K reversed its direction of migration, indicating the presence of protein. Treatment with venom phosphodiesterase liberated all of the radioactivity as pUp, suggesting that poliovirion RNA has a protein-pUp 5'-terminus. Treatment of virion RNA with T1 ribonuclease alone generated a proteinase K-sensitive oligoribonucleotide. Analysis of the oligoribonucleotide using ribonucleases A and U2 showed its structure to be protein-pU-U-A-A-A-A-C-A-G. Digests of replicative intermediate RNA contained sufficient protein-pUp to suggest that this structure is at the 5'-end of most nascent poliovirus RNA molecules. We suggest that a protein-nucleotide structure acts as a primer for initiating synthesis of poliovirus RNA."}
{"id": "PMID:191849", "title": "Evidence that the preoptic region is a receptive site for the dipsogenic effects of angiotensin II.", "content": "Drinking elicited by administering angiotensin II (ANG II) to the preoptic region with cannulae passing through the lateral ventricles was attenuated significantly when the ventricles or subfornical organ were pretreated with saralasin acetate (Sar1-Ala8-angiotensin II). If the cannulae in the preoptice region were angled to bypass the lateral ventricles water intake elicited by ANG II was less and pretreating the cerebral ventricles with saralasin acetate did not reduce the drinking response. The results suggest that the preoptic region may be a receptive site for ANG II in addition to the subfornical organ and/or cerebral ventricles.", "contents": "Evidence that the preoptic region is a receptive site for the dipsogenic effects of angiotensin II. Drinking elicited by administering angiotensin II (ANG II) to the preoptic region with cannulae passing through the lateral ventricles was attenuated significantly when the ventricles or subfornical organ were pretreated with saralasin acetate (Sar1-Ala8-angiotensin II). If the cannulae in the preoptice region were angled to bypass the lateral ventricles water intake elicited by ANG II was less and pretreating the cerebral ventricles with saralasin acetate did not reduce the drinking response. The results suggest that the preoptic region may be a receptive site for ANG II in addition to the subfornical organ and/or cerebral ventricles."}
{"id": "PMID:191850", "title": "Protein synthesis and amnesia: studies with emetine and pactamycin.", "content": "Two antibiotic inhibitors of protein synthesis, emetine and pactamycin, have been tested for their effects on cerebral and peripheral protein synthesis and amnesia. Peripherally administered emetine but not pactamycin inhibited cerebral protein synthesis, although this inhibition was lower than that observed with cycloheximide or anisomycin. Pactamycin had a lesser effect on adrenal protein synthesis than emetine. This was reflected in the ability of emetine but not pactamycin to block ACTH-induced corticosteroidogenesis. Anisomycin and cycloheximide caused amnesia in a passive avoidance task, whereas pactamycin and emetine did not. These results are inconsistent with the amnesia being due to inhibition of protein synthesis in a peripheral organ. They are also inconsistent with the amnesia being due to the suppression of an adrenocortical response as previously suggested. No obvious correlation between amnesia and the mechanism of protein synthesis was observed. The most parsimonious explanation is that inhibition of cerebral protein synthesis is necessary for amnesia.", "contents": "Protein synthesis and amnesia: studies with emetine and pactamycin. Two antibiotic inhibitors of protein synthesis, emetine and pactamycin, have been tested for their effects on cerebral and peripheral protein synthesis and amnesia. Peripherally administered emetine but not pactamycin inhibited cerebral protein synthesis, although this inhibition was lower than that observed with cycloheximide or anisomycin. Pactamycin had a lesser effect on adrenal protein synthesis than emetine. This was reflected in the ability of emetine but not pactamycin to block ACTH-induced corticosteroidogenesis. Anisomycin and cycloheximide caused amnesia in a passive avoidance task, whereas pactamycin and emetine did not. These results are inconsistent with the amnesia being due to inhibition of protein synthesis in a peripheral organ. They are also inconsistent with the amnesia being due to the suppression of an adrenocortical response as previously suggested. No obvious correlation between amnesia and the mechanism of protein synthesis was observed. The most parsimonious explanation is that inhibition of cerebral protein synthesis is necessary for amnesia."}
{"id": "PMID:191851", "title": "The influence of alpha-receptors on lordosis in the female rat.", "content": "The alpha-adrenergic agonist clonidine suppressed lordotic responding in spayed female rats brought into heat by estrogen and progesterone. The suppression was blocked by the alpha-antagonist yohimbine, but not by phenoxybenzamine or pimozide. The suppression was blocked by the alpha-antagonist yohimbine, but not by phenoxybenzamine or pimozide. Phenoxybenzamine itself had no suppressive effect on lordosis, though yohimbine did under some conditions. These results argue against an important facilitatory influence of norepinephrine on lordosis in the rat. Further, in comparison with the quite different findings recently reported from the guinea pig, they offer support for the presence of two different kinds of alpha-adrenergic receptors in the brain with different physiological functions.", "contents": "The influence of alpha-receptors on lordosis in the female rat. The alpha-adrenergic agonist clonidine suppressed lordotic responding in spayed female rats brought into heat by estrogen and progesterone. The suppression was blocked by the alpha-antagonist yohimbine, but not by phenoxybenzamine or pimozide. The suppression was blocked by the alpha-antagonist yohimbine, but not by phenoxybenzamine or pimozide. Phenoxybenzamine itself had no suppressive effect on lordosis, though yohimbine did under some conditions. These results argue against an important facilitatory influence of norepinephrine on lordosis in the rat. Further, in comparison with the quite different findings recently reported from the guinea pig, they offer support for the presence of two different kinds of alpha-adrenergic receptors in the brain with different physiological functions."}
{"id": "PMID:191852", "title": "Plasma corticosterone and brain catecholamines in stress: effect of psychotropic drugs.", "content": "In nonstressed rats, subcutaneous administration of haloperidol (HAL) and large doses of diazepam (DZ) increased plasma corticosterone (CS). Hypothalamic norepinephrine (NE) was lowered significantly by desmethylimipramine (DMI), HAL and, to a lesser extent, by DZ and phenobarbital (PHB). In rats pretreated with either DZ, DMI, HAL or PHB the restraint-induced rise of CS was diminished, DZ being most potent. CPZ had a variable effect, slightly increasing or decreasing the CS response. Pretreatment (16 hr) with pargyline (PA) did not affect the CS rise to stress. The reduction of hypothalamic NE evoked by restraint was attenuated by DZ, and to a lesser extent, by PHB and HAL. Restraint of PA-treated rats did not lower the PA-elevated hypothalamic NE. The stress-induced increase in hypothalamic dopamine was prevented by CPZ and, partially, by PHB. It is emphasized that the net plasma CS and brain catecholamine changes in response to stress are dependent on the drug-induced neuroendocrine feedback state prevalent immediately before commencement of the stress procedure.", "contents": "Plasma corticosterone and brain catecholamines in stress: effect of psychotropic drugs. In nonstressed rats, subcutaneous administration of haloperidol (HAL) and large doses of diazepam (DZ) increased plasma corticosterone (CS). Hypothalamic norepinephrine (NE) was lowered significantly by desmethylimipramine (DMI), HAL and, to a lesser extent, by DZ and phenobarbital (PHB). In rats pretreated with either DZ, DMI, HAL or PHB the restraint-induced rise of CS was diminished, DZ being most potent. CPZ had a variable effect, slightly increasing or decreasing the CS response. Pretreatment (16 hr) with pargyline (PA) did not affect the CS rise to stress. The reduction of hypothalamic NE evoked by restraint was attenuated by DZ, and to a lesser extent, by PHB and HAL. Restraint of PA-treated rats did not lower the PA-elevated hypothalamic NE. The stress-induced increase in hypothalamic dopamine was prevented by CPZ and, partially, by PHB. It is emphasized that the net plasma CS and brain catecholamine changes in response to stress are dependent on the drug-induced neuroendocrine feedback state prevalent immediately before commencement of the stress procedure."}
{"id": "PMID:191853", "title": "Anticonvulsant activity and selective inhibition of NAD-dependent oxidations by 1,4-disubstituted piperazines.", "content": "Several 1-(1-aryl-3-ethylthiocarbamido)-4-(arylaminothiocarbonyl)piperazines were synthesized, characterized by their sharp melting points and elemental analyses and evaluated for anticonvulsant activity. All disubstituted piperazines at a dose of 100 mg/kg i.p. provided 10-90% protection against pentylenetetrazol-induced convulsions in mice. These disubstituted piperazines selectively inhibited the in vitro oxidation of nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, alpha-ketoglutarate, beta-hydroxybutyrate and NADH by rat brain homogenates. The NAD-independent oxidation of succinate remained unaltered. The anticonvulsant activity possessed by disubstituted piperazines was unrelated with their ability to selectively inhibit respiratory activity of rat brain homogenates. Amongst 1-(substituted benzyl)-4-(substituted benzoyl)piperazines exhibiting central nervous system (1, 2) depressant activity it was found that 1-(2-chlorobenzyl)-4-(2-chlorobenzoyl)piperazine possessed maximum activity (2). The ability of piperazine carbamides (3) and piperazinothiocarbamides to possess anticonvulsant activity (4) prompted synthesis of 1-(1-aryl-3-ethylthiocarbamido)-4-(arylaminothiocarbonyl)piperazines and evaluation of their anticonvulsant activity. The effects of these disubstituted piperazines were also investigated on the in vitro respiratory activity of rat brain homogenates in an attempt to elucidate the biochemical mechanism of action for their anticonvulsant activity.", "contents": "Anticonvulsant activity and selective inhibition of NAD-dependent oxidations by 1,4-disubstituted piperazines. Several 1-(1-aryl-3-ethylthiocarbamido)-4-(arylaminothiocarbonyl)piperazines were synthesized, characterized by their sharp melting points and elemental analyses and evaluated for anticonvulsant activity. All disubstituted piperazines at a dose of 100 mg/kg i.p. provided 10-90% protection against pentylenetetrazol-induced convulsions in mice. These disubstituted piperazines selectively inhibited the in vitro oxidation of nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, alpha-ketoglutarate, beta-hydroxybutyrate and NADH by rat brain homogenates. The NAD-independent oxidation of succinate remained unaltered. The anticonvulsant activity possessed by disubstituted piperazines was unrelated with their ability to selectively inhibit respiratory activity of rat brain homogenates. Amongst 1-(substituted benzyl)-4-(substituted benzoyl)piperazines exhibiting central nervous system (1, 2) depressant activity it was found that 1-(2-chlorobenzyl)-4-(2-chlorobenzoyl)piperazine possessed maximum activity (2). The ability of piperazine carbamides (3) and piperazinothiocarbamides to possess anticonvulsant activity (4) prompted synthesis of 1-(1-aryl-3-ethylthiocarbamido)-4-(arylaminothiocarbonyl)piperazines and evaluation of their anticonvulsant activity. The effects of these disubstituted piperazines were also investigated on the in vitro respiratory activity of rat brain homogenates in an attempt to elucidate the biochemical mechanism of action for their anticonvulsant activity."}
{"id": "PMID:191854", "title": "Spasticity: its physiology and management. Part III. Identifying and assessing the mechanisms underlying spasticity.", "content": "Patients with spasticity may have similar motor signs and yet have completely different underlying neural mechanisms. This paper reviews some experimental tests which have been developed to detect and analyze excitatory excesses and inhibitory deficits giving rise to the abnormal motor signs of spasticity. Although at the present time these tests may not lend themselves to routine clinical application, their results are creating a body of knowledge which will become the foundation for diagnosis and treatment of spasticity in the future.", "contents": "Spasticity: its physiology and management. Part III. Identifying and assessing the mechanisms underlying spasticity. Patients with spasticity may have similar motor signs and yet have completely different underlying neural mechanisms. This paper reviews some experimental tests which have been developed to detect and analyze excitatory excesses and inhibitory deficits giving rise to the abnormal motor signs of spasticity. Although at the present time these tests may not lend themselves to routine clinical application, their results are creating a body of knowledge which will become the foundation for diagnosis and treatment of spasticity in the future."}
{"id": "PMID:191857", "title": "Functional characteristics of the intraspinal spread of viscerosomatic activity.", "content": "The functional characteristics of the intraspinal spread of the dual-component viscerosomatic reflex response were studied in chloralose-anaesthetized cats. In the region of the direct inputs of splanchnic afferents into the spinal cord, the initial part of the early (propriospinal) component is evoked by afflux from the extraspinal pathway in the sympathetic chain and has the shortest latent period. At segment Th8 to Th12 level this was 5.2--8.1 msec; cranially and caudally from this level it was longer. Activity spreading from the adjacent segments via intraspinal longitudinal systems also participates in the origin and course of the early component of the efferent discharge. The rate of ascending intraspinal irradiation in the thoracic region was 3.2--12 m/sec (6.6 +/- 2.4 m/sec). The rate of the descending spread of propriospinal activity in the thoracic region via intraspinal pathways was 3.6--18.3 m/sec (12.5 +/- 4.5 m/sec); in the lumbar region it was significantly lower -- 2.9--19.3 m/sec (7 +/- 4.5 m/sec). The latent period of the later component varied from 20 to 30 msec and displayed a cranio-caudal increase in length. The rate of the descending spread of the later component in the thoracic and lumbar cord did not differ significantly (20 +/- 10 m/sec and 22 +/- 13 m/sec respectively). The continuous splanchnic discharge in the lumbosacral region is correlated to the different rate of the intraspinal spread of the early and the late response and to their overlapping.", "contents": "Functional characteristics of the intraspinal spread of viscerosomatic activity. The functional characteristics of the intraspinal spread of the dual-component viscerosomatic reflex response were studied in chloralose-anaesthetized cats. In the region of the direct inputs of splanchnic afferents into the spinal cord, the initial part of the early (propriospinal) component is evoked by afflux from the extraspinal pathway in the sympathetic chain and has the shortest latent period. At segment Th8 to Th12 level this was 5.2--8.1 msec; cranially and caudally from this level it was longer. Activity spreading from the adjacent segments via intraspinal longitudinal systems also participates in the origin and course of the early component of the efferent discharge. The rate of ascending intraspinal irradiation in the thoracic region was 3.2--12 m/sec (6.6 +/- 2.4 m/sec). The rate of the descending spread of propriospinal activity in the thoracic region via intraspinal pathways was 3.6--18.3 m/sec (12.5 +/- 4.5 m/sec); in the lumbar region it was significantly lower -- 2.9--19.3 m/sec (7 +/- 4.5 m/sec). The latent period of the later component varied from 20 to 30 msec and displayed a cranio-caudal increase in length. The rate of the descending spread of the later component in the thoracic and lumbar cord did not differ significantly (20 +/- 10 m/sec and 22 +/- 13 m/sec respectively). The continuous splanchnic discharge in the lumbosacral region is correlated to the different rate of the intraspinal spread of the early and the late response and to their overlapping."}
{"id": "PMID:191858", "title": "Effect of various adaptational temperatures on oxidative capacity of the brown adipose tissue.", "content": "Changes in total weight, protein content and activity of cytochrome oxidase have been followed in the brown adipose tissue (BAT) of golden hamsters, white mice and white rats adapted to various temperatures. Important interspecies differences have been detected. The weight and the cytochrome oxidase activity of the BAT of the white mouse changes little under the influence of different adaptational temperatures, whereas in the white rat and in the golden hamster a decrease of adaptational temperature considerably increases the total weight, protein content and cytochrome oxidase activity of this organ. Different adaptational temperatures induce variable effects on the BAT of the golden hamster. Mild cold stimuli favour the accumulation of proteins and of oxidative enzymes, in particular. Severe cold stress also induces growth processes, so that the weight of the BAT increases proportionally to the total body weight of animals. The metabolic capacity of the BAT, measured as total cytochrome oxidase activity, changes substantially with decreasing temperature of adaptation in all species studied, increasing twice, six times and almost twelve times in the mouse, rat and golden hamster, respectively.", "contents": "Effect of various adaptational temperatures on oxidative capacity of the brown adipose tissue. Changes in total weight, protein content and activity of cytochrome oxidase have been followed in the brown adipose tissue (BAT) of golden hamsters, white mice and white rats adapted to various temperatures. Important interspecies differences have been detected. The weight and the cytochrome oxidase activity of the BAT of the white mouse changes little under the influence of different adaptational temperatures, whereas in the white rat and in the golden hamster a decrease of adaptational temperature considerably increases the total weight, protein content and cytochrome oxidase activity of this organ. Different adaptational temperatures induce variable effects on the BAT of the golden hamster. Mild cold stimuli favour the accumulation of proteins and of oxidative enzymes, in particular. Severe cold stress also induces growth processes, so that the weight of the BAT increases proportionally to the total body weight of animals. The metabolic capacity of the BAT, measured as total cytochrome oxidase activity, changes substantially with decreasing temperature of adaptation in all species studied, increasing twice, six times and almost twelve times in the mouse, rat and golden hamster, respectively."}
{"id": "PMID:191861", "title": "Dermal cylindroma (turban tumor). Case report.", "content": "We present an unusual case of massive dermal cylindroma (turban tumor), occupying the entire scalpand forehead. It was treated by a total scalping procedure and skin grafting in two stages. Additional tumors of the face, neck, chest, shoulders, and back were excised and closed. The nose was treated by shoving and dermabrasion, similar to a rhinophyma. The lip was treated by dermabrasion. There has been no evidence of recurrence in the scalp which was treated by excision and grafting. There is now a papular quality of the skin over the nose and on the uppler lip, indicating that regrowth may occur. The etiology, pathology, and a review of the literature are presented.", "contents": "Dermal cylindroma (turban tumor). Case report. We present an unusual case of massive dermal cylindroma (turban tumor), occupying the entire scalpand forehead. It was treated by a total scalping procedure and skin grafting in two stages. Additional tumors of the face, neck, chest, shoulders, and back were excised and closed. The nose was treated by shoving and dermabrasion, similar to a rhinophyma. The lip was treated by dermabrasion. There has been no evidence of recurrence in the scalp which was treated by excision and grafting. There is now a papular quality of the skin over the nose and on the uppler lip, indicating that regrowth may occur. The etiology, pathology, and a review of the literature are presented."}
{"id": "PMID:191863", "title": "Surgical treatment of hemifacial microsomia. (First and second branchial arch syndrome).", "content": "A review of 17 patients operated upon for unilateral hemifacial microsomia, and followed for up to 18 years, clarifies several principles of management. The management is facilitated by dysplasia predominance grouping, with the major functional deformity dictating the sequence of repair. Our surgical goals are: (1) provision of adequate upper airway; (2) preservation of normal teeth and adequate alveolar bone to achieve proper dental occlusion; (3) restoration of binaural hearing; (4) external ear construction; (5) acceptable facial symmetry; (6) balanced facial animation; and (7) a child with an acceptable self-image.", "contents": "Surgical treatment of hemifacial microsomia. (First and second branchial arch syndrome). A review of 17 patients operated upon for unilateral hemifacial microsomia, and followed for up to 18 years, clarifies several principles of management. The management is facilitated by dysplasia predominance grouping, with the major functional deformity dictating the sequence of repair. Our surgical goals are: (1) provision of adequate upper airway; (2) preservation of normal teeth and adequate alveolar bone to achieve proper dental occlusion; (3) restoration of binaural hearing; (4) external ear construction; (5) acceptable facial symmetry; (6) balanced facial animation; and (7) a child with an acceptable self-image."}
{"id": "PMID:191864", "title": "Malignant fibrous histiocytoma of the parapharyngeal space. Case report.", "content": "Of the large variety of tumors that may occur in the parapharyngeal space, malignant fibrous histiocytoma is one of the most rare. We present such a case and discuss the diagnosis, classification, and treatment.", "contents": "Malignant fibrous histiocytoma of the parapharyngeal space. Case report. Of the large variety of tumors that may occur in the parapharyngeal space, malignant fibrous histiocytoma is one of the most rare. We present such a case and discuss the diagnosis, classification, and treatment."}
{"id": "PMID:191866", "title": "[Effect of chlorimipramine on the so-called ponto-geniculo-occipitalactivity (PGO) in a primate, Papio hamadryas (author's transl)].", "content": "Three hamadryas adult baboons (female) received 24 daily injections of Chlorimipramine (1.7 mg/kg). The effects on sleep were nearly identical with the effects observed in man. PGO activity, recorded in the lateral geniculate nucleus, was much disturbed. The total number of PGO fell downward from the first recording. The number of PGO/min during paradoxial sleep was even more decreased. This fact suggests a selective influence of CL I on the mechanisms of PGO activity. Is the particular effect of importance to the treatment of depression symptoms?", "contents": "[Effect of chlorimipramine on the so-called ponto-geniculo-occipitalactivity (PGO) in a primate, Papio hamadryas (author's transl)]. Three hamadryas adult baboons (female) received 24 daily injections of Chlorimipramine (1.7 mg/kg). The effects on sleep were nearly identical with the effects observed in man. PGO activity, recorded in the lateral geniculate nucleus, was much disturbed. The total number of PGO fell downward from the first recording. The number of PGO/min during paradoxial sleep was even more decreased. This fact suggests a selective influence of CL I on the mechanisms of PGO activity. Is the particular effect of importance to the treatment of depression symptoms?"}
{"id": "PMID:191869", "title": "Ultrasonography of the genitourinary tract in children.", "content": "The author discusses the utility of ultrasound in investigating the genitourinary tract in neonates, infants, and children, and emphasizes the inter-dependence of ultrasonography and uroradiology.", "contents": "Ultrasonography of the genitourinary tract in children. The author discusses the utility of ultrasound in investigating the genitourinary tract in neonates, infants, and children, and emphasizes the inter-dependence of ultrasonography and uroradiology."}
{"id": "PMID:191870", "title": "Renal parenchymal infections in children.", "content": "The excretion urogram-nephrotomogram is the most important imaging study in the diagnosis of renal parenchymal infection in children. If renal parenchymal infections are discovered before significant necrosis has occurred, vigorous treatment with appropriate parenteral antibiotics may result in resolution without the need for surgical drainage.", "contents": "Renal parenchymal infections in children. The excretion urogram-nephrotomogram is the most important imaging study in the diagnosis of renal parenchymal infection in children. If renal parenchymal infections are discovered before significant necrosis has occurred, vigorous treatment with appropriate parenteral antibiotics may result in resolution without the need for surgical drainage."}
{"id": "PMID:191867", "title": "Sleep-waking changes in cardiac arrhythmia in a coronary care patient.", "content": "A single case is reported in whom ventricular cardiac arrhythmias were related to the occurrence of polygraphically verified sleep. A strong relationship was found to exist between the heart rate in any one minute and the number of premature ventricular contractions, with higher rates associated with a greater number of these ectopic beats.", "contents": "Sleep-waking changes in cardiac arrhythmia in a coronary care patient. A single case is reported in whom ventricular cardiac arrhythmias were related to the occurrence of polygraphically verified sleep. A strong relationship was found to exist between the heart rate in any one minute and the number of premature ventricular contractions, with higher rates associated with a greater number of these ectopic beats."}
{"id": "PMID:191871", "title": "Esophageal complications in the treatment of oat cell carcinoma with combined irradiation and chemotherapy.", "content": "A case of esophageal stenosis was noted in a patient treated with a combination of irradiation and chemotherapy for oat cell carcinoma. Review of the entire series of 22 patients revealed an unusually high rate (8/22) of esophagitis. These complications are discussed in relation to timing radiation dose and multidrug chemotherapy", "contents": "Esophageal complications in the treatment of oat cell carcinoma with combined irradiation and chemotherapy. A case of esophageal stenosis was noted in a patient treated with a combination of irradiation and chemotherapy for oat cell carcinoma. Review of the entire series of 22 patients revealed an unusually high rate (8/22) of esophagitis. These complications are discussed in relation to timing radiation dose and multidrug chemotherapy"}
{"id": "PMID:191872", "title": "Angiographic assessment of gross anatomy of hepatocellular cardinoma: comparison of celiac angiograms and liver pathology in 100 cases.", "content": "Of 190 sets selective celiac and/or hepatic angiograms obtained in patients with hepatocellular carcinoma (HCC), comparison with gross anatomy of the liver was subsequently made by autopsy in 77 and by surgery in 23. It was found that the gross anatomy of HCC can be assessed with certain accuracy by careful interpretation of the angiograms, because tumor vasculature and vascular alterations in the noncancerous parenchyma are closely related to the mode of tumor growth, size of tumor nodules and their distribution. Even a fibrous capsule of the tumor may be discerned as a radiolucent zone around the tumor contour. Diagnosis of the gross anatomical type of HCC is important to the selection of therapeutic measure and assessment of prognosis.", "contents": "Angiographic assessment of gross anatomy of hepatocellular cardinoma: comparison of celiac angiograms and liver pathology in 100 cases. Of 190 sets selective celiac and/or hepatic angiograms obtained in patients with hepatocellular carcinoma (HCC), comparison with gross anatomy of the liver was subsequently made by autopsy in 77 and by surgery in 23. It was found that the gross anatomy of HCC can be assessed with certain accuracy by careful interpretation of the angiograms, because tumor vasculature and vascular alterations in the noncancerous parenchyma are closely related to the mode of tumor growth, size of tumor nodules and their distribution. Even a fibrous capsule of the tumor may be discerned as a radiolucent zone around the tumor contour. Diagnosis of the gross anatomical type of HCC is important to the selection of therapeutic measure and assessment of prognosis."}
{"id": "PMID:191873", "title": "Ultrasonography and computed tomography in the diagnosis of homogeneous masses.", "content": "Ultrasonography can demonstrate the homogeneity, while CT can demonstrate the density of a mass lesion. If a mass appears echo-free at ultrasonography, but is denser than water at CT, a solid tumor with grossly uniform cellular structure (usually a lymphoma or sarcoma), or a hematoma or hemorrhagic cyst is likely. However, if the mass has water density at CT, a cystic lesion is confirmed. One case for each category is presented.", "contents": "Ultrasonography and computed tomography in the diagnosis of homogeneous masses. Ultrasonography can demonstrate the homogeneity, while CT can demonstrate the density of a mass lesion. If a mass appears echo-free at ultrasonography, but is denser than water at CT, a solid tumor with grossly uniform cellular structure (usually a lymphoma or sarcoma), or a hematoma or hemorrhagic cyst is likely. However, if the mass has water density at CT, a cystic lesion is confirmed. One case for each category is presented."}
{"id": "PMID:191875", "title": "Hydrocortisone inhibition of the bradykinin activation of human synovial fibroblasts.", "content": "Human synovial fibroblasts in culture respond to bradykinin with a 20-fold increment in intracellular cyclic AMP concentrations, however bradykinin does not directly activate adenylate cyclase activity in a particulate fraction derived from these cells. Bradykinin evokes a release of labeled arachidonic acid and prostaglandins E and F from synovial fibroblasts pre-labeled with 3H-arachidonic acid. Hydrocortisone inhibits the bradykinin induced increment in cyclic AMP and the release of arachidonic acid and prostaglandins E and F from synovial fibroblasts. Indomethacin, which also inhibits the cyclic AMP response to bradykinin, has no effect on the release of arachidonic acid from synovial fibroblasts. Indomethacin does, however, inhibit the quantity of prostaglandins released into the medium. These studies support the hypothesis that bradykinin does not activate human synovial fibroblast adenylate cyclase, but presumably activates a phospholipase whose products in turn result in the synthesis of prostaglandins. These and other investigations also suggest that a product(s) of the prostaglandin pathway causes the increment in cyclic AMP.", "contents": "Hydrocortisone inhibition of the bradykinin activation of human synovial fibroblasts. Human synovial fibroblasts in culture respond to bradykinin with a 20-fold increment in intracellular cyclic AMP concentrations, however bradykinin does not directly activate adenylate cyclase activity in a particulate fraction derived from these cells. Bradykinin evokes a release of labeled arachidonic acid and prostaglandins E and F from synovial fibroblasts pre-labeled with 3H-arachidonic acid. Hydrocortisone inhibits the bradykinin induced increment in cyclic AMP and the release of arachidonic acid and prostaglandins E and F from synovial fibroblasts. Indomethacin, which also inhibits the cyclic AMP response to bradykinin, has no effect on the release of arachidonic acid from synovial fibroblasts. Indomethacin does, however, inhibit the quantity of prostaglandins released into the medium. These studies support the hypothesis that bradykinin does not activate human synovial fibroblast adenylate cyclase, but presumably activates a phospholipase whose products in turn result in the synthesis of prostaglandins. These and other investigations also suggest that a product(s) of the prostaglandin pathway causes the increment in cyclic AMP."}
{"id": "PMID:191876", "title": "Modulation of human platelet adenylate cyclase by prostacyclin (PGX).", "content": "Prostacyclin (PGX) (57)-9-deoxy-6,9alpha-epoxy-delta5-PGF1alpha has been found to be a potent stimulator of cAMP accumulation in platelets than PGE1. The prostacyclin stimulation of platelet cAMP accumulation can be antagonized by the prostaglandin endoperoxide PGH2, and a PGH2-induced platelet aggregation is antagonized by prostacyclin. A model of platelet homeostasis is proposed that suggests platelet aggregation is controlled by a balance between the adenylate cyclase stimulating activity of prostacyclin, and the cAMP lowering activity of PGH2.", "contents": "Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostacyclin (PGX) (57)-9-deoxy-6,9alpha-epoxy-delta5-PGF1alpha has been found to be a potent stimulator of cAMP accumulation in platelets than PGE1. The prostacyclin stimulation of platelet cAMP accumulation can be antagonized by the prostaglandin endoperoxide PGH2, and a PGH2-induced platelet aggregation is antagonized by prostacyclin. A model of platelet homeostasis is proposed that suggests platelet aggregation is controlled by a balance between the adenylate cyclase stimulating activity of prostacyclin, and the cAMP lowering activity of PGH2."}
{"id": "PMID:191877", "title": "Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets.", "content": "Prostacyclin (PGX) strikingly increases cyclic AMP concentrations in human platelets. Prostacyclin is approximately 10 times more active than PGD2, 30 times more active than PGE1 and more than 1000 times more active than its stable end product, 6-oxo-PGF1alpha. These results correlate well with the anti-aggregating activity of prostacyclin, compared with PGE1 and PGD2.", "contents": "Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostacyclin (PGX) strikingly increases cyclic AMP concentrations in human platelets. Prostacyclin is approximately 10 times more active than PGD2, 30 times more active than PGE1 and more than 1000 times more active than its stable end product, 6-oxo-PGF1alpha. These results correlate well with the anti-aggregating activity of prostacyclin, compared with PGE1 and PGD2."}
{"id": "PMID:191880", "title": "Effect of papaverine on cyclic AMP, calcium uptake and force of contraction in isolated guinea-pig auricles.", "content": "The effects of papaverine on cyclic AMP (c-AMP), 45 calcium uptake and force of contraction were studied in electrically stimulated left guinea-pig auricles. Papaverine (2 x 10(-6) - 2 x 10(-5)M produced a concentration-dependent positive inotropic effect which was not affected by 10(-7) M propranolol. Papaverine (10(-5)M increased cyclic AMP; this effect developed faster than the increase in twitch tension. Papaverine (10(-5)M) enhanced 45calcium uptake. These results are taken to support the idea of a causative series of interactions between a papaverine induced increase in c-AMP, calcium uptake and force of contraction.", "contents": "Effect of papaverine on cyclic AMP, calcium uptake and force of contraction in isolated guinea-pig auricles. The effects of papaverine on cyclic AMP (c-AMP), 45 calcium uptake and force of contraction were studied in electrically stimulated left guinea-pig auricles. Papaverine (2 x 10(-6) - 2 x 10(-5)M produced a concentration-dependent positive inotropic effect which was not affected by 10(-7) M propranolol. Papaverine (10(-5)M increased cyclic AMP; this effect developed faster than the increase in twitch tension. Papaverine (10(-5)M) enhanced 45calcium uptake. These results are taken to support the idea of a causative series of interactions between a papaverine induced increase in c-AMP, calcium uptake and force of contraction."}
{"id": "PMID:191879", "title": "[Herpetic etiology of gastric and duodenal ulcer. II. Study in humans].", "content": "By inducing experimental ulcers in the rabbit with the type 1 Herpes simplex strain, isolated from the herpes vesicles from a vagotomized patient, the authors demonstrate the protective role of vagotomy, the ulcerogenic capacity of the virus, which can be considered as an etiological factor of human gastroduodenal ulceration. They also discuss the possibilities for a new medical therapy of this disturbance.", "contents": "[Herpetic etiology of gastric and duodenal ulcer. II. Study in humans]. By inducing experimental ulcers in the rabbit with the type 1 Herpes simplex strain, isolated from the herpes vesicles from a vagotomized patient, the authors demonstrate the protective role of vagotomy, the ulcerogenic capacity of the virus, which can be considered as an etiological factor of human gastroduodenal ulceration. They also discuss the possibilities for a new medical therapy of this disturbance."}
{"id": "PMID:191886", "title": "[The risk of grave evolution of tuberculosis in  young children (under 2 years of age)].", "content": "Between 1971 and 1972, 22% of all children under two years with tuberculosis presented with severe forms of the disease (meningitis, miliaria, caseous forms). In the period 1974-1975, although the number of cases in the group was reduced by half, the severe forms still represented 20,4% of the total. The risk of severe evolution of tuberculosis decreases rapidly, from 55--66% in the first months of life. to 14,2--15,5% at 1--2 years. The risk of death in children aged between 0 and 2 years with tuberculosis (all forms) was of 26,6--58,3% between 0 and 5 months but only 4,5--9,3% in the second year of life. The risk of death in young children with severe forms of tuberculosis was as high as 70--76,7% in those under the age of 6 months. The source of infection was identified in 72,4--76,4% of the severe cases. At the onset of the disease only 57,1% of the sources were known, while 42,9% were discovered later, by epidemiologic investigations. An analysis of cause for a severe evolution of tuberculosis in young children led to the conclusion that BCG vaccination should be performed systematically at birth, and that tuberculin skin test be carried out in all hospitalized children, regardless the diagnosis. They also recommend the use of anamnestic data concerning the possible existence of tuberculosis cases in the families of patients, performing of radiologic controls in young mothers etc. In the case of infants that come into a close contact at a very early age with parents, or other relatives suffering with tuberculosis, chemoprophylaxis with two associated tuberculostatics is indicated.", "contents": "[The risk of grave evolution of tuberculosis in  young children (under 2 years of age)]. Between 1971 and 1972, 22% of all children under two years with tuberculosis presented with severe forms of the disease (meningitis, miliaria, caseous forms). In the period 1974-1975, although the number of cases in the group was reduced by half, the severe forms still represented 20,4% of the total. The risk of severe evolution of tuberculosis decreases rapidly, from 55--66% in the first months of life. to 14,2--15,5% at 1--2 years. The risk of death in children aged between 0 and 2 years with tuberculosis (all forms) was of 26,6--58,3% between 0 and 5 months but only 4,5--9,3% in the second year of life. The risk of death in young children with severe forms of tuberculosis was as high as 70--76,7% in those under the age of 6 months. The source of infection was identified in 72,4--76,4% of the severe cases. At the onset of the disease only 57,1% of the sources were known, while 42,9% were discovered later, by epidemiologic investigations. An analysis of cause for a severe evolution of tuberculosis in young children led to the conclusion that BCG vaccination should be performed systematically at birth, and that tuberculin skin test be carried out in all hospitalized children, regardless the diagnosis. They also recommend the use of anamnestic data concerning the possible existence of tuberculosis cases in the families of patients, performing of radiologic controls in young mothers etc. In the case of infants that come into a close contact at a very early age with parents, or other relatives suffering with tuberculosis, chemoprophylaxis with two associated tuberculostatics is indicated."}
{"id": "PMID:191887", "title": "[Immunological aspects of workers exposed to the risk of silicogenesis].", "content": "Comparative studies were performed, of changes of serum proteins and IgG, IgA and IgM immunoglobulins in workers exposed to silicogenic dust. Depending on their response to tuberculin testing (2 U of PPD) these subjects were classified in negative and hyperergic. In both groups there was found a decreased albumin concentration in the serum and high alpha-2 globulin. In hyperergic subjects there was noted a slight increase of beta globulins and a significant rise in the titer of gammaglobulins. Immunoglobulins G showed a significant rise in hyperallergic subjects and slightly decreased in tuberculin negative ones, without attaining a level of immunologic deficiency. In both groups IgM immunoglobulins were significantly lowered, while IgA immunoglobulins were occasionally increased, although there was no positive correlation with tuberculin allergy. In three cases there was a slight IgA deficiency.", "contents": "[Immunological aspects of workers exposed to the risk of silicogenesis]. Comparative studies were performed, of changes of serum proteins and IgG, IgA and IgM immunoglobulins in workers exposed to silicogenic dust. Depending on their response to tuberculin testing (2 U of PPD) these subjects were classified in negative and hyperergic. In both groups there was found a decreased albumin concentration in the serum and high alpha-2 globulin. In hyperergic subjects there was noted a slight increase of beta globulins and a significant rise in the titer of gammaglobulins. Immunoglobulins G showed a significant rise in hyperallergic subjects and slightly decreased in tuberculin negative ones, without attaining a level of immunologic deficiency. In both groups IgM immunoglobulins were significantly lowered, while IgA immunoglobulins were occasionally increased, although there was no positive correlation with tuberculin allergy. In three cases there was a slight IgA deficiency."}
{"id": "PMID:191889", "title": "[Immediate results of strictly supervised, intermittent treatment with rifampicin and ethambutol in patients with chronic pulmonary tuberculosis].", "content": "Of the 118 patients suffering from chronic pulmonary tuberculosis, living within the district of the T\u00eergu Mure\u015f Tuberculosis Dispensary, 100 accepted a strictly surveyed treatment and of these 90 continued for at least 6 months. The present paper reports on the immediate radiologic and bacteriological results and the factors influencing them. The following conclusions were drawn: 1) A 2/7 Rifampicin/Etambutol strictly supervised treatment is the most efficient method for neutralizing chronic bacillary sources. 2) The age and origin of the patients, the duration and extent of the pulmonary process, duration of the treatment and associated diseases are the factors that furnish the prognosis of the expected results. 3) Apart from the very good results obtained the method cannot solve all chronic cases and the classical antiepidemic measures must be applied in continuation.", "contents": "[Immediate results of strictly supervised, intermittent treatment with rifampicin and ethambutol in patients with chronic pulmonary tuberculosis]. Of the 118 patients suffering from chronic pulmonary tuberculosis, living within the district of the T\u00eergu Mure\u015f Tuberculosis Dispensary, 100 accepted a strictly surveyed treatment and of these 90 continued for at least 6 months. The present paper reports on the immediate radiologic and bacteriological results and the factors influencing them. The following conclusions were drawn: 1) A 2/7 Rifampicin/Etambutol strictly supervised treatment is the most efficient method for neutralizing chronic bacillary sources. 2) The age and origin of the patients, the duration and extent of the pulmonary process, duration of the treatment and associated diseases are the factors that furnish the prognosis of the expected results. 3) Apart from the very good results obtained the method cannot solve all chronic cases and the classical antiepidemic measures must be applied in continuation."}
{"id": "PMID:191890", "title": "[Frequency of isolation of tuberculous bacilli as a function of some mechanical factors in patients with pulmonary tuberculosis].", "content": "A series of mechanical factors, such as postural changes and every day movements, favour mobilization of bronchoalveolar secretions and, hence, offer greater chanses of detecting the tuberculosis bacillus. It is recommended to collect, in out-patient units, two sputum samples, one in the morning and the second several hours later, after beginning the day's work.", "contents": "[Frequency of isolation of tuberculous bacilli as a function of some mechanical factors in patients with pulmonary tuberculosis]. A series of mechanical factors, such as postural changes and every day movements, favour mobilization of bronchoalveolar secretions and, hence, offer greater chanses of detecting the tuberculosis bacillus. It is recommended to collect, in out-patient units, two sputum samples, one in the morning and the second several hours later, after beginning the day's work."}
{"id": "PMID:191891", "title": "[Value of methods used in the etiological diagnosis of pleural exudates].", "content": "A study was carried out on 64 cases of pleural exsudates, i.e. 23 of neoplastic origin, 13 tuberculous, 10 with various etiologies and 8 the cause of which could not be determined. In all cases pleural biopsy puncture was performed, once or several times, the histologic examination confirming 80% of the cases of tuberculosis and 40% of the cancer cases. Biochemical methods are orientative, their significance increasing when the other probability tests give convergent results.", "contents": "[Value of methods used in the etiological diagnosis of pleural exudates]. A study was carried out on 64 cases of pleural exsudates, i.e. 23 of neoplastic origin, 13 tuberculous, 10 with various etiologies and 8 the cause of which could not be determined. In all cases pleural biopsy puncture was performed, once or several times, the histologic examination confirming 80% of the cases of tuberculosis and 40% of the cancer cases. Biochemical methods are orientative, their significance increasing when the other probability tests give convergent results."}
{"id": "PMID:191892", "title": "[Changes in time of the microbial flora in bronchopulmonary infections].", "content": "The authors carried out a study on 100 cases with broncho-pulmonary infections in two different periods: 1963--1964 and 1973--1974. Changes in the microbial flora were investigated, as well as the sensitivity of germs to antibiotics. An increase was noted in the number of chronic bronchitis and a decrease in the number of pneumonia cases. In the microbial flora there was a constant proportion of staphylococcus, streptococcus and coli strains. The proportion of micrococci decreased with time and pneumococci practically disappeared, being replaced by klebsiella germs. Sensitivity to penicilin remained almost identical while that to chloramphenicol decreased significantly, as well as sensitivity to tetracycline and neomycine. The practical conclusion is that in some cases the application of penicilin treatment, before the results of the antibiogram are available appears to be justified.", "contents": "[Changes in time of the microbial flora in bronchopulmonary infections]. The authors carried out a study on 100 cases with broncho-pulmonary infections in two different periods: 1963--1964 and 1973--1974. Changes in the microbial flora were investigated, as well as the sensitivity of germs to antibiotics. An increase was noted in the number of chronic bronchitis and a decrease in the number of pneumonia cases. In the microbial flora there was a constant proportion of staphylococcus, streptococcus and coli strains. The proportion of micrococci decreased with time and pneumococci practically disappeared, being replaced by klebsiella germs. Sensitivity to penicilin remained almost identical while that to chloramphenicol decreased significantly, as well as sensitivity to tetracycline and neomycine. The practical conclusion is that in some cases the application of penicilin treatment, before the results of the antibiogram are available appears to be justified."}
{"id": "PMID:191896", "title": "[Histochemical and histoenzymatic studies of chick-embryo tibial rudiments cultured in vitro in the presence of bovine growth hormones].", "content": "The AA. have studied the effect of the bovine GH on the cellular and intercellular components of the chick embryo tibias cultured organotypically. They have observed a strong increase of the proliferative activity of the chondroblasts such as showed by a stronger uptake of the tritiated timidine by traited tibias in comparison with the control tibias. The chondroblasts of the traited tibias show an increase of some enzymatic activities connected with the aerobic cycle and of the UDPG-DH, connected with the uronic acids cycle. In the amorphous matrix of the traited tibias they have showed a greater polimerisation and sulfation of the condroitinesulfate A and C, which, almost exclusively, constitute the mucopolisaccharidic component of the matrix.", "contents": "[Histochemical and histoenzymatic studies of chick-embryo tibial rudiments cultured in vitro in the presence of bovine growth hormones]. The AA. have studied the effect of the bovine GH on the cellular and intercellular components of the chick embryo tibias cultured organotypically. They have observed a strong increase of the proliferative activity of the chondroblasts such as showed by a stronger uptake of the tritiated timidine by traited tibias in comparison with the control tibias. The chondroblasts of the traited tibias show an increase of some enzymatic activities connected with the aerobic cycle and of the UDPG-DH, connected with the uronic acids cycle. In the amorphous matrix of the traited tibias they have showed a greater polimerisation and sulfation of the condroitinesulfate A and C, which, almost exclusively, constitute the mucopolisaccharidic component of the matrix."}
{"id": "PMID:191893", "title": "[Correlations of ventilation measurements with alpha 1-antitrypsin deficiency chronic suppurative bronchopneumopathies].", "content": "The corrleations of ventilometry and alpha-1-antitrypsin deficiency were studied in a lot of 105 patients with chronic obstructive bronchopneumopathy associated with various forms of chronic pulmonary suppuration. Alpha-1-antitripsin deficiency was determined by Erikson's gelatin film test, simplified by Keith et al. Ventilation dysfunctions were found in 79% of the cases, predominantly obstructive, mixed, advanced or severe. Alpha-1-antitrypsin deficiency was detected in 11.4% of the patients as against 4.1% in the controls, the deficiency being more accentuated in the mixed (75%) and obstructive (25%) ventilation dysfunctions. Determination of alpha-1-antitrypsin deficiency, corroborated with other investigations may supply useful information for detecting a predisposition and for the evolutive prognosis of these respiratory diseases.", "contents": "[Correlations of ventilation measurements with alpha 1-antitrypsin deficiency chronic suppurative bronchopneumopathies]. The corrleations of ventilometry and alpha-1-antitrypsin deficiency were studied in a lot of 105 patients with chronic obstructive bronchopneumopathy associated with various forms of chronic pulmonary suppuration. Alpha-1-antitripsin deficiency was determined by Erikson's gelatin film test, simplified by Keith et al. Ventilation dysfunctions were found in 79% of the cases, predominantly obstructive, mixed, advanced or severe. Alpha-1-antitrypsin deficiency was detected in 11.4% of the patients as against 4.1% in the controls, the deficiency being more accentuated in the mixed (75%) and obstructive (25%) ventilation dysfunctions. Determination of alpha-1-antitrypsin deficiency, corroborated with other investigations may supply useful information for detecting a predisposition and for the evolutive prognosis of these respiratory diseases."}
{"id": "PMID:191895", "title": "[Active-evolutive pulmonary tuberculosis with negative tuberculin reaction].", "content": "In a lot of 452 patients with various forms of tuberculosis, in various locations, the authors have investigated the efficiency of tests currently employed in detecting tuberculin sensitivity (intradermoreaction to PPD, the test to sensitines and the Ustvedt test), in relation with several immunologic tests performed in vitro (index of lymphoblastogenesis to PPD and/or phytohaemagglutinin, leucocyte migration inhibition test, and the rosette test). It was noted that the two groups of investigations give similar results when tuberculin reactions are positive and intense. Under the conventionally admitted threshold of tuberculinic allergy the test of blastic transformation of lymphocytes, and especially the leucocyte migration inhibition tests are still positive and may be considered as a valuable means for measuring infra-tuberculinic allergy, as well as for the diagnosis of latent tuberculous infections.", "contents": "[Active-evolutive pulmonary tuberculosis with negative tuberculin reaction]. In a lot of 452 patients with various forms of tuberculosis, in various locations, the authors have investigated the efficiency of tests currently employed in detecting tuberculin sensitivity (intradermoreaction to PPD, the test to sensitines and the Ustvedt test), in relation with several immunologic tests performed in vitro (index of lymphoblastogenesis to PPD and/or phytohaemagglutinin, leucocyte migration inhibition test, and the rosette test). It was noted that the two groups of investigations give similar results when tuberculin reactions are positive and intense. Under the conventionally admitted threshold of tuberculinic allergy the test of blastic transformation of lymphocytes, and especially the leucocyte migration inhibition tests are still positive and may be considered as a valuable means for measuring infra-tuberculinic allergy, as well as for the diagnosis of latent tuberculous infections."}
{"id": "PMID:191897", "title": "[Antagonism between focal epilepsy and taurine administered by cortical perfusion].", "content": "The therapeutic action of taurine cortical perfusion was tested in cats affected with Premarin and cobalt cortical epileptogenic foci. In all animals taurine provoked the disappearance of EEG epileptic abnormalities. In the case of Premarin focus the effect appeared more quickly than in the cobalt one. This different time-course, according to previous reports on the antiepileptic action of the parenteral administration of the amino acid, suggests the hypothesis of a taurine direct inhibitory action against Premarin focus and, on the contrary, a mediated action towards the cobalt's. The latter might be related to the metabolic production of some taurine derivative.", "contents": "[Antagonism between focal epilepsy and taurine administered by cortical perfusion]. The therapeutic action of taurine cortical perfusion was tested in cats affected with Premarin and cobalt cortical epileptogenic foci. In all animals taurine provoked the disappearance of EEG epileptic abnormalities. In the case of Premarin focus the effect appeared more quickly than in the cobalt one. This different time-course, according to previous reports on the antiepileptic action of the parenteral administration of the amino acid, suggests the hypothesis of a taurine direct inhibitory action against Premarin focus and, on the contrary, a mediated action towards the cobalt's. The latter might be related to the metabolic production of some taurine derivative."}
{"id": "PMID:191900", "title": "Importance of associated viral and bacterial infections in the production of acute pneumonias.", "content": "Bacteriologic and virologic investigations carried out in a group of 85 patients with acute pneumonia have allowed the determination of the etiologic agent in 52.9% of the cases. Of these, 40% showed combined viral and bacterial infections. Mixovirus infections were frequently associated with staphylococcic ones (7 out of 8 cases) and adenovirus infections with the pneumococcic ones (6 out of 7 cases). The most severe and longdrawn clinical pictures with frequent pleuropulmonary complications (in 22.24% of the cases) had a biphasic evolution in only 6 of the 18 pneumonias of mixed etiology. For their high frequency and their clinical peculiarities, mixed etiology pneumonias might be considered as distinct clinical entities.", "contents": "Importance of associated viral and bacterial infections in the production of acute pneumonias. Bacteriologic and virologic investigations carried out in a group of 85 patients with acute pneumonia have allowed the determination of the etiologic agent in 52.9% of the cases. Of these, 40% showed combined viral and bacterial infections. Mixovirus infections were frequently associated with staphylococcic ones (7 out of 8 cases) and adenovirus infections with the pneumococcic ones (6 out of 7 cases). The most severe and longdrawn clinical pictures with frequent pleuropulmonary complications (in 22.24% of the cases) had a biphasic evolution in only 6 of the 18 pneumonias of mixed etiology. For their high frequency and their clinical peculiarities, mixed etiology pneumonias might be considered as distinct clinical entities."}
{"id": "PMID:191905", "title": "[Biochemistry of collagen and locomotor apparatus. Hereditary diseases of the connective tissue and rheumatic diseases (3)].", "content": "In inflammatory granuloma, synovial sclerosis or inflammation and in Dupuytren's contracture, the neocollagen contains chains and/or transverse links that are characteristic of rapidly growing immature tissues. In arthrosis, a conversion of collagen synthesis towards a cutaneous type may occur. The destruction of cartilage in rheumatoid arthritis is brought about by a specific collagenase that originates from the inflamed synovial membrane. Finally, certain forms of osteoporosis may be due to alterations of the osseous collagen which impair the mechanism of calcification.", "contents": "[Biochemistry of collagen and locomotor apparatus. Hereditary diseases of the connective tissue and rheumatic diseases (3)]. In inflammatory granuloma, synovial sclerosis or inflammation and in Dupuytren's contracture, the neocollagen contains chains and/or transverse links that are characteristic of rapidly growing immature tissues. In arthrosis, a conversion of collagen synthesis towards a cutaneous type may occur. The destruction of cartilage in rheumatoid arthritis is brought about by a specific collagenase that originates from the inflamed synovial membrane. Finally, certain forms of osteoporosis may be due to alterations of the osseous collagen which impair the mechanism of calcification."}
{"id": "PMID:191906", "title": "[Bronchial adenoma].", "content": "Twenty-four patients with bronchial adenoma seen over a 20-year period are reviewed. Follow-up data was available in all patients. They included 19 with carcinoid, 2 with adenoid-cystic carcinoma, and 3 with muco-epidermoid carcinoma. Recurrent pulmonary infection, cough and hemoptysis were the most common clinical manifestations. Surgical resection was performed in all but one patient, who was treated by irradiation; bronchoplastic and conservative resectional procedures were used in 5 patients with carcinoid adenoma. Carcinoid tumors are considered to be very slowly-growing malignant neoplasms that sometimes give rise to metastases to regional lymph nodes. Such metastases were present in only one patient. All patients are alive and well. Adenoid-cystic carcinoma is a more aggressive tumor with a tendency to recur. Much of the difficulty in its treatment is due to its close proximity to the bifurcation of the trachea. One patient was operated upon three times for local recurrences and ultimately died from respiratory failure after the third operation. The other patient received radiation therapy with cobalt and is well, without recurrence, 3 years after the treatment. The 3 muco-epidermoid carcinomas were histologically similar to such tumors of salivary glands but behaved clinically like highly malignant tumors, no patients surviving 8 months after resection. The term bronchial adenoma is a misnomer. The neoplasms grouped under this heading should be called carcinoid adenoma, adenoid-cystic carcinoma, and muco-epidermoid carcinoma and considered as separate entities, since the ultimate course and prognosis is definitely different.", "contents": "[Bronchial adenoma]. Twenty-four patients with bronchial adenoma seen over a 20-year period are reviewed. Follow-up data was available in all patients. They included 19 with carcinoid, 2 with adenoid-cystic carcinoma, and 3 with muco-epidermoid carcinoma. Recurrent pulmonary infection, cough and hemoptysis were the most common clinical manifestations. Surgical resection was performed in all but one patient, who was treated by irradiation; bronchoplastic and conservative resectional procedures were used in 5 patients with carcinoid adenoma. Carcinoid tumors are considered to be very slowly-growing malignant neoplasms that sometimes give rise to metastases to regional lymph nodes. Such metastases were present in only one patient. All patients are alive and well. Adenoid-cystic carcinoma is a more aggressive tumor with a tendency to recur. Much of the difficulty in its treatment is due to its close proximity to the bifurcation of the trachea. One patient was operated upon three times for local recurrences and ultimately died from respiratory failure after the third operation. The other patient received radiation therapy with cobalt and is well, without recurrence, 3 years after the treatment. The 3 muco-epidermoid carcinomas were histologically similar to such tumors of salivary glands but behaved clinically like highly malignant tumors, no patients surviving 8 months after resection. The term bronchial adenoma is a misnomer. The neoplasms grouped under this heading should be called carcinoid adenoma, adenoid-cystic carcinoma, and muco-epidermoid carcinoma and considered as separate entities, since the ultimate course and prognosis is definitely different."}
{"id": "PMID:191907", "title": "Hybridization in situ of SV40 plaques: detection of recombinant SV40 virus carrying specific sequences of nonviral DNA.", "content": "The detection and recovery of SV40 genomes containing foreign DNA sequences can be facilitated, and the risk of accidental dispersal reduced, by in situ hybridization and radioautography.", "contents": "Hybridization in situ of SV40 plaques: detection of recombinant SV40 virus carrying specific sequences of nonviral DNA. The detection and recovery of SV40 genomes containing foreign DNA sequences can be facilitated, and the risk of accidental dispersal reduced, by in situ hybridization and radioautography."}
{"id": "PMID:191908", "title": "Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents.", "content": "A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled us to design a new class of potent and specific inhibitors. These compounds, carboxyalkanoyl and mercaptoalkanoyl derivatives of proline, inhibit the contractile response of guinea pig ileal strip to angiotensin I and augment its response to bradykinin. When administered orally to rats, these agents inhibit the pressor effect of angiotensin I, augment the vasodepressor effect of bradykinin, and lower blood pressure in a model of renovascular hypertension.", "contents": "Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled us to design a new class of potent and specific inhibitors. These compounds, carboxyalkanoyl and mercaptoalkanoyl derivatives of proline, inhibit the contractile response of guinea pig ileal strip to angiotensin I and augment its response to bradykinin. When administered orally to rats, these agents inhibit the pressor effect of angiotensin I, augment the vasodepressor effect of bradykinin, and lower blood pressure in a model of renovascular hypertension."}
{"id": "PMID:191909", "title": "Sesquiterpene antitumor agents: inhibitors of cellular metabolism.", "content": "Helenalin and tenulin injected into CF1 male mice bearing Ehrlich ascites tumors inhibit DNA synthesis and DNA polymerase enzymatic activity in the tumor cells. Helenalin inhibited protein synthesis. Both drugs increased the concentration of adenosine 3',5'-monophosphate, and interfered with glycolytic and mitochondrial energy processes. Cholesterol synthesis was also inhibited, resulting in lower serum cholesterol levels in tumor-bearing animals. Data obtained in vitro indicate that the cyclopentenone-bearing sesquiterpene lactone and related compounds do not alkylate puring bases of nucleic acids but rather undergo a Michael-type addition reaction with the sulfhydryl groups of reduced glutathione and l-cysteine. Thus, the inhibition of cellular enzyme activities and metabolism that has been observed with these drugs might be explained by the occurrence of a Michael-type teaction.", "contents": "Sesquiterpene antitumor agents: inhibitors of cellular metabolism. Helenalin and tenulin injected into CF1 male mice bearing Ehrlich ascites tumors inhibit DNA synthesis and DNA polymerase enzymatic activity in the tumor cells. Helenalin inhibited protein synthesis. Both drugs increased the concentration of adenosine 3',5'-monophosphate, and interfered with glycolytic and mitochondrial energy processes. Cholesterol synthesis was also inhibited, resulting in lower serum cholesterol levels in tumor-bearing animals. Data obtained in vitro indicate that the cyclopentenone-bearing sesquiterpene lactone and related compounds do not alkylate puring bases of nucleic acids but rather undergo a Michael-type addition reaction with the sulfhydryl groups of reduced glutathione and l-cysteine. Thus, the inhibition of cellular enzyme activities and metabolism that has been observed with these drugs might be explained by the occurrence of a Michael-type teaction."}
{"id": "PMID:191910", "title": "A phospholipid derivative of cytosine arabinoside and its conversion to phosphatidylinositol by animal tissue.", "content": "We have synthesized an analog (ara-CDP-DL-dipalmitin) of cytidine diphosphate diglyceride (CDP-diglyceride) in which the antitumor drug, cytosine arabinoside, is substituted for the cytidine moiety. Enzymes in rat and human liver convert this analog to phosphatidylinositol, thereby releasing cytosine arabinoside-5'-monophosphate, an obligatory intermediate in the activation of cytosine arabinoside. Unlike cytidine diphosphate diglyceride, however, ara-CDP-DL-diapalmitin is not an efficient substrate for phosphatidylglycerophosphate synthesis in liver or phosphatidylserine in Escherichia coli. The antitumor activity of ara-CDP-DL-dipalmitin in mice bearing L5178Y leukemia is described.", "contents": "A phospholipid derivative of cytosine arabinoside and its conversion to phosphatidylinositol by animal tissue. We have synthesized an analog (ara-CDP-DL-dipalmitin) of cytidine diphosphate diglyceride (CDP-diglyceride) in which the antitumor drug, cytosine arabinoside, is substituted for the cytidine moiety. Enzymes in rat and human liver convert this analog to phosphatidylinositol, thereby releasing cytosine arabinoside-5'-monophosphate, an obligatory intermediate in the activation of cytosine arabinoside. Unlike cytidine diphosphate diglyceride, however, ara-CDP-DL-diapalmitin is not an efficient substrate for phosphatidylglycerophosphate synthesis in liver or phosphatidylserine in Escherichia coli. The antitumor activity of ara-CDP-DL-dipalmitin in mice bearing L5178Y leukemia is described."}
{"id": "PMID:191911", "title": "Antigen-antibody reactions in rat brain sites induce transient changes in drinking behavior.", "content": "The septum or hypothalamus of rat brain was injected through implanted cannulas with antibody against membrane antigens in the rat brain or with antibody against exogenous soluble antigens (such as ovalbumin) followed by the specific antigen. Both immunological systems produced a moderate but highly significant decrease in drinking by thirsty rats. This phenomenon is suggested as an experimental model for behavioral disorders resulting from nondegenerative, immunological processes in the brain.", "contents": "Antigen-antibody reactions in rat brain sites induce transient changes in drinking behavior. The septum or hypothalamus of rat brain was injected through implanted cannulas with antibody against membrane antigens in the rat brain or with antibody against exogenous soluble antigens (such as ovalbumin) followed by the specific antigen. Both immunological systems produced a moderate but highly significant decrease in drinking by thirsty rats. This phenomenon is suggested as an experimental model for behavioral disorders resulting from nondegenerative, immunological processes in the brain."}
{"id": "PMID:191912", "title": "[Changes in Achilles tendon reflex under influence of non endocrine factors].", "content": "Numerous physiopathological processes such as diurnal variations sex, age, pregnancy, muscular effort, diseases and drugs modify the Achilles reflexogram. Their multiplicity explains the difficulty of general interpretation of changes in the reflexogram which bring into play the energy reserves of the muscle cell and its potassium content.", "contents": "[Changes in Achilles tendon reflex under influence of non endocrine factors]. Numerous physiopathological processes such as diurnal variations sex, age, pregnancy, muscular effort, diseases and drugs modify the Achilles reflexogram. Their multiplicity explains the difficulty of general interpretation of changes in the reflexogram which bring into play the energy reserves of the muscle cell and its potassium content."}
{"id": "PMID:191920", "title": "[Topographic diagnosis of hypertensive pheochromocytoma].", "content": "In a series of 9 cases of hypertensive pheochromocytoma, the author noted in five of them abolition of the lower abdominal skin reflex on the same side as the tumour. They were in four cases suprarenal pheochromocytomas and in the fifth case an ectopic paraganglioma of Zuckerland's organ. In 3 cases, the abolished reflex became normal and equal to that on the opposite side after removal of the tumour. In two others, it remained abolished. In 4 patients, most of the other abdominal skin reflexes, expecially those, on the opposite side, very brisk before the operation, became normal afterwards. The author concludes that in cases of hypertensive pheochromocytoma, careful study of the abdominal skin reflexes may provide a useful contribution to topographic diagnosis.", "contents": "[Topographic diagnosis of hypertensive pheochromocytoma]. In a series of 9 cases of hypertensive pheochromocytoma, the author noted in five of them abolition of the lower abdominal skin reflex on the same side as the tumour. They were in four cases suprarenal pheochromocytomas and in the fifth case an ectopic paraganglioma of Zuckerland's organ. In 3 cases, the abolished reflex became normal and equal to that on the opposite side after removal of the tumour. In two others, it remained abolished. In 4 patients, most of the other abdominal skin reflexes, expecially those, on the opposite side, very brisk before the operation, became normal afterwards. The author concludes that in cases of hypertensive pheochromocytoma, careful study of the abdominal skin reflexes may provide a useful contribution to topographic diagnosis."}
{"id": "PMID:191921", "title": "[Phreno-celiac disease and merycism in adults].", "content": "In this paper are described two new examples of a peculiar semiological association of which the authors have already reported a case, and in which occured simultaneously a phreno-coeliac disease and merycism since childhood. Strong epigastric pains accompained the merycism. In these two cases, the compression of the coeliac trunk by the median arcuate ligament of the diaphragm was important; in one case existed besides a compressive stenosis of the superior mesenteric artery. After the surgical liberation of the coeliac artery and the peri-coeliac neurectomy in one case, all symptoms relieved. This good result persists after twelve months. Because of the rarity of the phreno-coeliac disease and of this type of merycism, the authors think that this association is not accidental, but the result of a new nosological association.", "contents": "[Phreno-celiac disease and merycism in adults]. In this paper are described two new examples of a peculiar semiological association of which the authors have already reported a case, and in which occured simultaneously a phreno-coeliac disease and merycism since childhood. Strong epigastric pains accompained the merycism. In these two cases, the compression of the coeliac trunk by the median arcuate ligament of the diaphragm was important; in one case existed besides a compressive stenosis of the superior mesenteric artery. After the surgical liberation of the coeliac artery and the peri-coeliac neurectomy in one case, all symptoms relieved. This good result persists after twelve months. Because of the rarity of the phreno-coeliac disease and of this type of merycism, the authors think that this association is not accidental, but the result of a new nosological association."}
{"id": "PMID:191922", "title": "[Severe hemolytic jaundice and Wilson's disease].", "content": "The onset of spontaneous hemolytic jaundice in a young subject should lead to the search for Wilson's disease when clinical examination reveals cirrhosis. This hemolysis may evolve in the form of severe jaundice to a stage where the cirrhosis remains usually latent or well tolerated. The intervention of a toxic, allergic of infective factor liable to produce a hepatic lesion which frees a dose of copper sufficient to trigger off hemolysis, is discussed. The mechanism of the latter, that of the coagulation disorders observed, liver cell failure and widespread intravascular coagulation, are analysed in this paper and compared with data in the literature. The dramatic character of the case indicates that it is necessary to treat as a routine with penicillamine all homozygous forms of Wilson's disease.", "contents": "[Severe hemolytic jaundice and Wilson's disease]. The onset of spontaneous hemolytic jaundice in a young subject should lead to the search for Wilson's disease when clinical examination reveals cirrhosis. This hemolysis may evolve in the form of severe jaundice to a stage where the cirrhosis remains usually latent or well tolerated. The intervention of a toxic, allergic of infective factor liable to produce a hepatic lesion which frees a dose of copper sufficient to trigger off hemolysis, is discussed. The mechanism of the latter, that of the coagulation disorders observed, liver cell failure and widespread intravascular coagulation, are analysed in this paper and compared with data in the literature. The dramatic character of the case indicates that it is necessary to treat as a routine with penicillamine all homozygous forms of Wilson's disease."}
{"id": "PMID:191923", "title": "[Endomyocardial biopsy by venous route. Our initial results].", "content": "The authors report their experience of right ventricular endomyocardial biopsy by the technic of Caves and Schulz. The instrument which consists of a spiral metallic catheter covered with synthetic material, includes at one end a hand lever and at the other end a biopsy forceps 3 mm in diameter. It is introduced through the skin into the right internal jugular vein then pushed under direct vision with an image intensifier upto the tip of the right ventricle. The angle of the distal part of the bioptome may be freely modified before use. Passage across the tricuspid orifice from the right atrium is usually easy. 30 good quality samples were thus taken from 10 patients with various forms of heart disease. There were no complications. The simplicity, rapidity and benign nature of this technic are emphasised together with its use in the diagnosis of myocardiopathies.", "contents": "[Endomyocardial biopsy by venous route. Our initial results]. The authors report their experience of right ventricular endomyocardial biopsy by the technic of Caves and Schulz. The instrument which consists of a spiral metallic catheter covered with synthetic material, includes at one end a hand lever and at the other end a biopsy forceps 3 mm in diameter. It is introduced through the skin into the right internal jugular vein then pushed under direct vision with an image intensifier upto the tip of the right ventricle. The angle of the distal part of the bioptome may be freely modified before use. Passage across the tricuspid orifice from the right atrium is usually easy. 30 good quality samples were thus taken from 10 patients with various forms of heart disease. There were no complications. The simplicity, rapidity and benign nature of this technic are emphasised together with its use in the diagnosis of myocardiopathies."}
{"id": "PMID:191927", "title": "[Criteria of identification of schistosomiasis caused by Schistosoma hamatobium and S. mansoni (486 patients: 275 case of schistosomiasis)].", "content": "Out of a total of 486 patients who originated from French Equatorial Africa, from the West Indies or from the Indian Ocean, the authors identified 275 cases of schistosomiasis of which 230 were due to S. Hematobium and 45 to S. Mansoni. The diagnostic methods were biopsy of the rectal mucosa, immunofluorescence, in the West Indians, examination of the stools, in the Africans examination of the urine, intravenous urography and less often cystoscopy. The value of these investigations was studied in each case, then by comparison with one another and with data in the literature. The most valuable investigation was biopsy of the rectum, better in Africans than examination of the urine, immunofluorescence and better than cystoscopy when this was possible.", "contents": "[Criteria of identification of schistosomiasis caused by Schistosoma hamatobium and S. mansoni (486 patients: 275 case of schistosomiasis)]. Out of a total of 486 patients who originated from French Equatorial Africa, from the West Indies or from the Indian Ocean, the authors identified 275 cases of schistosomiasis of which 230 were due to S. Hematobium and 45 to S. Mansoni. The diagnostic methods were biopsy of the rectal mucosa, immunofluorescence, in the West Indians, examination of the stools, in the Africans examination of the urine, intravenous urography and less often cystoscopy. The value of these investigations was studied in each case, then by comparison with one another and with data in the literature. The most valuable investigation was biopsy of the rectum, better in Africans than examination of the urine, immunofluorescence and better than cystoscopy when this was possible."}
{"id": "PMID:191928", "title": "[Value of bone marrow biopsy in solid tumors. Apropos of 96 cases].", "content": "This study of 96 bone biopsies carried out in 84 patients with various malignant solid tumours showed 27 normal bone marrows, 21 hypoplastic marrows, 34 irritant marrows and 14 metastatic marrows. All the patients in the last group and 75% of those with signs of irritation already had other metastases. Tolerance to chemotherapy was better in the normal marrows than in the other cases. There was a significant relationship between the irritant or metastatic or metastatic aspect and the existence of peripheral leucoerythroblastosis (metastatic marrows) or increased platelets (irritant appearances). A significant difference existed during the first five months of survival between these cases with a metastatic marrow and those with an iritant marrow. Bone biopsy should, in our opinion, form part of the routine investigation of cancer patients. It may identify metasine investigation of cancer patients. It may identify metastases where radiography and bone scans have failed.", "contents": "[Value of bone marrow biopsy in solid tumors. Apropos of 96 cases]. This study of 96 bone biopsies carried out in 84 patients with various malignant solid tumours showed 27 normal bone marrows, 21 hypoplastic marrows, 34 irritant marrows and 14 metastatic marrows. All the patients in the last group and 75% of those with signs of irritation already had other metastases. Tolerance to chemotherapy was better in the normal marrows than in the other cases. There was a significant relationship between the irritant or metastatic or metastatic aspect and the existence of peripheral leucoerythroblastosis (metastatic marrows) or increased platelets (irritant appearances). A significant difference existed during the first five months of survival between these cases with a metastatic marrow and those with an iritant marrow. Bone biopsy should, in our opinion, form part of the routine investigation of cancer patients. It may identify metasine investigation of cancer patients. It may identify metastases where radiography and bone scans have failed."}
{"id": "PMID:191929", "title": "[10 cases of multiple malignant tumors].", "content": "The authors report ten cases of multiple malignant tumours noted on a general medical unit : 4 cases of chronic lymphatic leukemia associated with one visceral carcinoma. One case of polycythemia associated with a bifocal colonic carcinoma and a skin carcinoma. 5 double carcinomas mainly bronchial and digestive. They recall the general characteristics of these multiple carcinomas and discuss their pathogenesis with special reference to factors of immunodepression and genetic factors.", "contents": "[10 cases of multiple malignant tumors]. The authors report ten cases of multiple malignant tumours noted on a general medical unit : 4 cases of chronic lymphatic leukemia associated with one visceral carcinoma. One case of polycythemia associated with a bifocal colonic carcinoma and a skin carcinoma. 5 double carcinomas mainly bronchial and digestive. They recall the general characteristics of these multiple carcinomas and discuss their pathogenesis with special reference to factors of immunodepression and genetic factors."}
{"id": "PMID:191932", "title": "The FTA-ABS test: a diagnostic help or hindrance?", "content": "The fluorescent treponemal antibody absorption (FTA-ABS) test, an excellent confirmatory treponemal test, has been used increasingly for syphilis screening and case detection. To evaluate its performance as an initial test, we did Venereal Disease Research Laboratory (VDRL) slide and FTA-ABS tests on 1,043 patients suspected of having syphilis. When retested in both a local and a reference laboratory, sera from 226 patients with borderline or reactive results demonstrated interlaboratory consistency for the VDRL but not the FTA-ABS. Borderline FTA-ABS results correlated poorly with the diagnosis of syphilis in both laboratories; a reactive FTA-ABS test correlated well only in the reference laboratory. Performance of the test appeared to be diminished by its use in a low-prevalence population and by seemingly minor alterations in the test procedure at the local laboratory.", "contents": "The FTA-ABS test: a diagnostic help or hindrance? The fluorescent treponemal antibody absorption (FTA-ABS) test, an excellent confirmatory treponemal test, has been used increasingly for syphilis screening and case detection. To evaluate its performance as an initial test, we did Venereal Disease Research Laboratory (VDRL) slide and FTA-ABS tests on 1,043 patients suspected of having syphilis. When retested in both a local and a reference laboratory, sera from 226 patients with borderline or reactive results demonstrated interlaboratory consistency for the VDRL but not the FTA-ABS. Borderline FTA-ABS results correlated poorly with the diagnosis of syphilis in both laboratories; a reactive FTA-ABS test correlated well only in the reference laboratory. Performance of the test appeared to be diminished by its use in a low-prevalence population and by seemingly minor alterations in the test procedure at the local laboratory."}
{"id": "PMID:191933", "title": "Studies of serum testosterone and its reduction products.", "content": "Levels of serum testosterone (T) and its metabolites dihydrotestosterone (D) and androstanediol (A) measured by a competitive protein binding method were as follows, respectively: in adult males (mean +/- 1 SD), 435 +/- 114, 41 +/- 11, 43 +/- 12 ng/100 ml; in adult females, 30 +/- 14, 18 +/- 8, 18 +/-9; in prepubertal males, 14 +/- 7, 10 +/- 4, 10 +/- 5; and in prepubertal females, 15 +/- 4, 9 +/- 4, 12 +/- 7. These studies are presented to establish relative normal values for these metabolites in various age groups. To help elucidate the role of testosterone metabolites in certain androgenic disorders, patients with idiopathic hirsutism and gonadal disorders were subjected to short-term stimulation with HCG or ACTH and suppression with dexamethasone. Most patients with idiopathic hirsutism showed suppression of all three androgens (particularly androstanediol). Further comparisons of these androgens may aid in elucidating the problem in idiopathic hirsutism.", "contents": "Studies of serum testosterone and its reduction products. Levels of serum testosterone (T) and its metabolites dihydrotestosterone (D) and androstanediol (A) measured by a competitive protein binding method were as follows, respectively: in adult males (mean +/- 1 SD), 435 +/- 114, 41 +/- 11, 43 +/- 12 ng/100 ml; in adult females, 30 +/- 14, 18 +/- 8, 18 +/-9; in prepubertal males, 14 +/- 7, 10 +/- 4, 10 +/- 5; and in prepubertal females, 15 +/- 4, 9 +/- 4, 12 +/- 7. These studies are presented to establish relative normal values for these metabolites in various age groups. To help elucidate the role of testosterone metabolites in certain androgenic disorders, patients with idiopathic hirsutism and gonadal disorders were subjected to short-term stimulation with HCG or ACTH and suppression with dexamethasone. Most patients with idiopathic hirsutism showed suppression of all three androgens (particularly androstanediol). Further comparisons of these androgens may aid in elucidating the problem in idiopathic hirsutism."}
{"id": "PMID:191934", "title": "Predictors of the duration of infectious mononucleosis.", "content": "The clinical course of infectious mononucleosis was monitored in 122 patients to determine predictors of duration of illness. Gastrointestinal symptoms and palatal petechiae were associated with a prolonged recovery period. Multiple regression analysis of quantitative data identified the number of days from onset of symptoms to diagnosis as the only statistically significant indicator. Liver enzymes, white blood cell count, percentage atypical lymphocytes and heterophil titer had no prognostic value for the length of illness.", "contents": "Predictors of the duration of infectious mononucleosis. The clinical course of infectious mononucleosis was monitored in 122 patients to determine predictors of duration of illness. Gastrointestinal symptoms and palatal petechiae were associated with a prolonged recovery period. Multiple regression analysis of quantitative data identified the number of days from onset of symptoms to diagnosis as the only statistically significant indicator. Liver enzymes, white blood cell count, percentage atypical lymphocytes and heterophil titer had no prognostic value for the length of illness."}
{"id": "PMID:191935", "title": "Anorexia nervosa: a combined therapeutic approach.", "content": "Ten female patients with a diagnosis of anorexia nervosa were treated with a combination of behavior modification and psychotherapy and, when appropriate, psychotropic medication. All patients had favorable weight gain and improvement in adjustment during hospitalization. Later crises for each patient thus far have not significantly affected their weight. Three case histories illustrate the method used. The interrelationship between weight gain and the process in psychotherapy is illustrated and the psychopathologic features typical of this patient population are discussed. We conclude that the combined therapeutic method described is an effective and appropriate approach to the treatment of patients with anorexia nervosa.", "contents": "Anorexia nervosa: a combined therapeutic approach. Ten female patients with a diagnosis of anorexia nervosa were treated with a combination of behavior modification and psychotherapy and, when appropriate, psychotropic medication. All patients had favorable weight gain and improvement in adjustment during hospitalization. Later crises for each patient thus far have not significantly affected their weight. Three case histories illustrate the method used. The interrelationship between weight gain and the process in psychotherapy is illustrated and the psychopathologic features typical of this patient population are discussed. We conclude that the combined therapeutic method described is an effective and appropriate approach to the treatment of patients with anorexia nervosa."}
{"id": "PMID:191936", "title": "Benign tumors of the esophagus: experience with 20 cases.", "content": "Benign tumors of the esophagus are rare and require an alert suspicion for early diagnosis. These tumors may not cause symtoms before attaining large size, yet they may prove fatal when small. Because of the possibility of malignancy and their tendency to obstruct, benign tumors of the esophagus should be resected when diagnosed. This report details our experience in 20 patients with benign esophageal tumors seen at Emory University Hospital between 1955 and 1975. There were 15 men and five women in the group, ranging in age from 17 to 75 years. The tumor series included 13 leiomyomas, four cysts, two cases of multiple polyps, and one case of granular cell myoblastoma. Six of the tumors were asymptomatic; the remaining 14 had symptoms of dysphagia, pain, and hematemesis. In one instance, episodic hematemesis and melena were so severe that they produced hemorrhagic shock. Characteristic radiologic features helped in making the preoperative diagnosis in 18 of the 20 cases. Two patients had coexisting disease masking the presence of the esophageal tumor. Seventeen patients had surgical resection. There were no operative deaths and follow-up results have been satisfactory.", "contents": "Benign tumors of the esophagus: experience with 20 cases. Benign tumors of the esophagus are rare and require an alert suspicion for early diagnosis. These tumors may not cause symtoms before attaining large size, yet they may prove fatal when small. Because of the possibility of malignancy and their tendency to obstruct, benign tumors of the esophagus should be resected when diagnosed. This report details our experience in 20 patients with benign esophageal tumors seen at Emory University Hospital between 1955 and 1975. There were 15 men and five women in the group, ranging in age from 17 to 75 years. The tumor series included 13 leiomyomas, four cysts, two cases of multiple polyps, and one case of granular cell myoblastoma. Six of the tumors were asymptomatic; the remaining 14 had symptoms of dysphagia, pain, and hematemesis. In one instance, episodic hematemesis and melena were so severe that they produced hemorrhagic shock. Characteristic radiologic features helped in making the preoperative diagnosis in 18 of the 20 cases. Two patients had coexisting disease masking the presence of the esophageal tumor. Seventeen patients had surgical resection. There were no operative deaths and follow-up results have been satisfactory."}
{"id": "PMID:191937", "title": "Intracranial meningioma containing metastatic foci.", "content": "A case of a woman with carcinoma of the lung who died as the result of an expanding fluid mass over the right cerebral hemisphere is presented. Adjacent to this fluid mass was a small meningioma containing a metastatic focus. This was one of many metastases from the primary bronchiolar carcinoma. Photomicrographs are presented and comments regarding tumor collison are given.", "contents": "Intracranial meningioma containing metastatic foci. A case of a woman with carcinoma of the lung who died as the result of an expanding fluid mass over the right cerebral hemisphere is presented. Adjacent to this fluid mass was a small meningioma containing a metastatic focus. This was one of many metastases from the primary bronchiolar carcinoma. Photomicrographs are presented and comments regarding tumor collison are given."}
{"id": "PMID:191939", "title": "Nephroblastoma in the Black child: a review of treatment in the Johannesburg Paediatric Tumour Clinic.", "content": "Twenty-five Black children with nephroblastoma who were referred to the Paediatric Tumour Clinic during the preceding 4 years, are reviewed. Results indicate that in the case of a locally advanced, fixed, primary tumour, initial surgery, even if it is combined with chemotherapy, may be a factor in the rapid postoperative development of multiple pulmonary metastases. Pre-operative irradiation appeared to be advantageous for these patients. Long-term chemotherapy holds no advantage over short-term chemotherapy.", "contents": "Nephroblastoma in the Black child: a review of treatment in the Johannesburg Paediatric Tumour Clinic. Twenty-five Black children with nephroblastoma who were referred to the Paediatric Tumour Clinic during the preceding 4 years, are reviewed. Results indicate that in the case of a locally advanced, fixed, primary tumour, initial surgery, even if it is combined with chemotherapy, may be a factor in the rapid postoperative development of multiple pulmonary metastases. Pre-operative irradiation appeared to be advantageous for these patients. Long-term chemotherapy holds no advantage over short-term chemotherapy."}
{"id": "PMID:191940", "title": "Paget's disease of the vulva: a case report.", "content": "A patient with Paget's disease of the vulva is described. A brief review of some recent literature underlines the controversy regarding the histogenesis of the disease, and stresses the use of simple vulvectomy in its treatment. The importance of ruling out concomitant carcinoma is also stressed.", "contents": "Paget's disease of the vulva: a case report. A patient with Paget's disease of the vulva is described. A brief review of some recent literature underlines the controversy regarding the histogenesis of the disease, and stresses the use of simple vulvectomy in its treatment. The importance of ruling out concomitant carcinoma is also stressed."}
{"id": "PMID:191941", "title": "Parasitic infections in Black children in an endemic schistosomiasis area in Natal.", "content": "Urine and stool specimens from 856 school children aged from 7 to 20 years, and from 80 preschool children, were examined for Schistosoma haematobium and intestinal helminths and protozoa. S. haematobium was present in 57% with a peak of 81% in 13-14-year-old children. Peak intensity preceded peak incidence and egg loads gradually decreased with age. There was no clear-cut difference between boys and girls with regard to intestinal parasites, nor was there a close correlation between the incidence of Schistosoma spp. and that of the intestinal parasites. There was a considerable reduction in the incidence of Ascaris lumbricoides and Trichuris trichiura infestation with age.", "contents": "Parasitic infections in Black children in an endemic schistosomiasis area in Natal. Urine and stool specimens from 856 school children aged from 7 to 20 years, and from 80 preschool children, were examined for Schistosoma haematobium and intestinal helminths and protozoa. S. haematobium was present in 57% with a peak of 81% in 13-14-year-old children. Peak intensity preceded peak incidence and egg loads gradually decreased with age. There was no clear-cut difference between boys and girls with regard to intestinal parasites, nor was there a close correlation between the incidence of Schistosoma spp. and that of the intestinal parasites. There was a considerable reduction in the incidence of Ascaris lumbricoides and Trichuris trichiura infestation with age."}
{"id": "PMID:191945", "title": "Kidney transplantation for the uremic diabetic patient.", "content": "Although the diabetic patient is at high risk for transplantation and the progression of cardiovascular disease continues, results of our experience indicate that kidney transplantation can be performed with only slightly less favorable results than in the nondiabetic patients. We have found that the survival rate achieved by diabetics who receive a kidney graft is superior to that achieved by diabetic patients who receive dialysis. We also believe that some of the secondary complications of diabetes, which are aggravated by uremia, will be improved and that successful vocational rehabilitation is possible in the majority of diabetic patients.", "contents": "Kidney transplantation for the uremic diabetic patient. Although the diabetic patient is at high risk for transplantation and the progression of cardiovascular disease continues, results of our experience indicate that kidney transplantation can be performed with only slightly less favorable results than in the nondiabetic patients. We have found that the survival rate achieved by diabetics who receive a kidney graft is superior to that achieved by diabetic patients who receive dialysis. We also believe that some of the secondary complications of diabetes, which are aggravated by uremia, will be improved and that successful vocational rehabilitation is possible in the majority of diabetic patients."}
{"id": "PMID:191947", "title": "Radiation-induced fibrosarcoma following treatment for breast cancer.", "content": "A patient with radiation-induced fibrosarcoma following mastectomy and postoperative radiation for bilateral breast carcinoma is described. Only six such cases have been reported in the literature. In this patient erosion of the axillary artery produced massive hemorrhage, and emergency transthoracic ligation of the subclavian artery caused gangrene of the extremity and empyema and sepsis. Interscapulothoracic amputation not only was life-saving but offered the patient a reasonable chance for long-term survival. Only aggressive surgical management can salvage a patient with radiation-induced sarcoma.", "contents": "Radiation-induced fibrosarcoma following treatment for breast cancer. A patient with radiation-induced fibrosarcoma following mastectomy and postoperative radiation for bilateral breast carcinoma is described. Only six such cases have been reported in the literature. In this patient erosion of the axillary artery produced massive hemorrhage, and emergency transthoracic ligation of the subclavian artery caused gangrene of the extremity and empyema and sepsis. Interscapulothoracic amputation not only was life-saving but offered the patient a reasonable chance for long-term survival. Only aggressive surgical management can salvage a patient with radiation-induced sarcoma."}
{"id": "PMID:191948", "title": "Viral infections in renal transplant donors and their recipients: a prospective study.", "content": "The majority of renal allograft recipients develop viral infections, usually with cytomegalovirus (CMV). Their source if virus has not been defined clearly; one possibility if the transplanted kidney itself. To explore this, prospective viral studies were performed on 28 living related donor-recipient pairs. Donors did not have clinical illnesses and viruses were not recovered from throat, urine, or renal tissue, but five (18%) had fourfold rises in antibody titers to herpes group viruses. During the 6 months after transplantation, 24 recipients (86%) had viral infections, 18 of which were associated with CMV. There was no correlation between specific titer rises in the donors and infections in the recipients. Recipients with dual viral infections had more severe clinical courses than those with single infections or with no infection. Recipients with complement-fixing (CF) antibodies to CMV pretransplant had a higher incidence of CMV infections than recipients without pretransplant antibody. Three of seven recipients who lacked CF antibody to CMV and whose donors were seropositive developed clinical illnesses associated with CMV. Latent virus might have been transmitted with the transplanted kidney in these instances, but since lack of CF antibody does not rule out previous CMV infection, the CMV could have been of recipient origin. We conclude that the donor organ is a source of virus for few renal transplant recipients.", "contents": "Viral infections in renal transplant donors and their recipients: a prospective study. The majority of renal allograft recipients develop viral infections, usually with cytomegalovirus (CMV). Their source if virus has not been defined clearly; one possibility if the transplanted kidney itself. To explore this, prospective viral studies were performed on 28 living related donor-recipient pairs. Donors did not have clinical illnesses and viruses were not recovered from throat, urine, or renal tissue, but five (18%) had fourfold rises in antibody titers to herpes group viruses. During the 6 months after transplantation, 24 recipients (86%) had viral infections, 18 of which were associated with CMV. There was no correlation between specific titer rises in the donors and infections in the recipients. Recipients with dual viral infections had more severe clinical courses than those with single infections or with no infection. Recipients with complement-fixing (CF) antibodies to CMV pretransplant had a higher incidence of CMV infections than recipients without pretransplant antibody. Three of seven recipients who lacked CF antibody to CMV and whose donors were seropositive developed clinical illnesses associated with CMV. Latent virus might have been transmitted with the transplanted kidney in these instances, but since lack of CF antibody does not rule out previous CMV infection, the CMV could have been of recipient origin. We conclude that the donor organ is a source of virus for few renal transplant recipients."}
{"id": "PMID:191951", "title": "Experience with regional vaccination against swine fever in enzootic areas for limited periods using C-strain virus.", "content": "In three areas of the Netherlands with a high incidence of swine fever all pigs over two weeks old were vaccinated with the so-called \"Chinese\" (C)-strain of vaccine virus. The mass vaccination at the start of each compaign was supplemented thereafter by vaccination of young stock at the age of 6 to 8 weeks and of all pigs introduced from outside. In one area vaccination was pursed for three years, and in two areas for one year. Vaccination was compulsory and supported by stamping out of affected herds and the application of the usual veterinary police measures. The number of outbreaks in the vaccinated areas declined from two weeks after the start of the campaign and clinical disease had diappeared after five months. During this period outbreaks related to vaccination were diagnosed in each area. Some outbreaks were due to vaccination procedures which probably caused the spread of virus from congenitally infected litters to susceptible piglets, which had lost maternal antibodies. Only one \"vaccine break\" was diagnosed. Outbreaks of swine fever, due to the presence of residual virus in the designated areas, have not been reported up to two years after vaccination was discontinued. The campaigns have shown that swine fever can be eradicated from enzootic areas by a strict vaccination regime pursued for one year.", "contents": "Experience with regional vaccination against swine fever in enzootic areas for limited periods using C-strain virus. In three areas of the Netherlands with a high incidence of swine fever all pigs over two weeks old were vaccinated with the so-called \"Chinese\" (C)-strain of vaccine virus. The mass vaccination at the start of each compaign was supplemented thereafter by vaccination of young stock at the age of 6 to 8 weeks and of all pigs introduced from outside. In one area vaccination was pursed for three years, and in two areas for one year. Vaccination was compulsory and supported by stamping out of affected herds and the application of the usual veterinary police measures. The number of outbreaks in the vaccinated areas declined from two weeks after the start of the campaign and clinical disease had diappeared after five months. During this period outbreaks related to vaccination were diagnosed in each area. Some outbreaks were due to vaccination procedures which probably caused the spread of virus from congenitally infected litters to susceptible piglets, which had lost maternal antibodies. Only one \"vaccine break\" was diagnosed. Outbreaks of swine fever, due to the presence of residual virus in the designated areas, have not been reported up to two years after vaccination was discontinued. The campaigns have shown that swine fever can be eradicated from enzootic areas by a strict vaccination regime pursued for one year."}
{"id": "PMID:191953", "title": "[An atypical form of Aujezky's disease after vaccination (author's transl].", "content": "Four atypical case of Aujezky's disease in dogs are described. Two weeks before the outbreak of the disease, the dogs had been vaccinated with a live tissue culture vaccin, based on the Bartha strain. By culturevirus (cytopathogenic effect) the Bartha vaccin was identified and a vaccination reaction was proved. Vaccination with this must be discouraged.", "contents": "[An atypical form of Aujezky's disease after vaccination (author's transl]. Four atypical case of Aujezky's disease in dogs are described. Two weeks before the outbreak of the disease, the dogs had been vaccinated with a live tissue culture vaccin, based on the Bartha strain. By culturevirus (cytopathogenic effect) the Bartha vaccin was identified and a vaccination reaction was proved. Vaccination with this must be discouraged."}
{"id": "PMID:191954", "title": "[Aujeszky's disease in goats (authors transl)].", "content": "The small number of cases of Aujeszky's disease in goats referred to in the literature is stressed, and an outbreak in goats causing many deaths is reported. The flock of goats concerned was occasionally housed in a barn during the night in which there also were fattening pigs. The first deaths occurred without previous symptoms, the animals being found dead in the morning. In subsequent cases, symptoms were observed which continued for a few or several hours and consisted in agitation, lying down and rising, screaming plaintively, profuse sweating and, in the terminal stage, spasms and paralysis. Pruritus was not observed in any of the animals. Of the fifteen goats which had been housed in the pig-sty, thirteen died during ten days. In the same period, only one out of forty pigs died, and the others showed anorexia and somnolence for a couple of days but soon recovered. In two goats studied, the virus of Aujeszky's disease was isolated from the central nervous system. It is suggested that, in cases of disease or death in ruminants occurring in the proximity of pigs, there should primarily be a strong suspicion of Aujeszky's disease, regardless of the symptoms observed.", "contents": "[Aujeszky's disease in goats (authors transl)]. The small number of cases of Aujeszky's disease in goats referred to in the literature is stressed, and an outbreak in goats causing many deaths is reported. The flock of goats concerned was occasionally housed in a barn during the night in which there also were fattening pigs. The first deaths occurred without previous symptoms, the animals being found dead in the morning. In subsequent cases, symptoms were observed which continued for a few or several hours and consisted in agitation, lying down and rising, screaming plaintively, profuse sweating and, in the terminal stage, spasms and paralysis. Pruritus was not observed in any of the animals. Of the fifteen goats which had been housed in the pig-sty, thirteen died during ten days. In the same period, only one out of forty pigs died, and the others showed anorexia and somnolence for a couple of days but soon recovered. In two goats studied, the virus of Aujeszky's disease was isolated from the central nervous system. It is suggested that, in cases of disease or death in ruminants occurring in the proximity of pigs, there should primarily be a strong suspicion of Aujeszky's disease, regardless of the symptoms observed."}
{"id": "PMID:191957", "title": "Stomach cancer of a 14-year-old boy with ataxia-telangiectasia.", "content": "A 14-year-old boy with ataxia-telangiectasis died of pneumonia, stomach cancer and its diffuse metastasis. The onset of walding gait was noticed from 3 years of age. Immune globulin including IgA was normal or slightly increased. Main autopsy findings were: old cancerous ulcer of 1.4 X 2.3 cm at the lesser curvature, and diffuse cancer infiltration over ulcer surface to serous membrane. The tumor was diagnosed histologically as adenocarcinoma tabulare mucocellulare.", "contents": "Stomach cancer of a 14-year-old boy with ataxia-telangiectasia. A 14-year-old boy with ataxia-telangiectasis died of pneumonia, stomach cancer and its diffuse metastasis. The onset of walding gait was noticed from 3 years of age. Immune globulin including IgA was normal or slightly increased. Main autopsy findings were: old cancerous ulcer of 1.4 X 2.3 cm at the lesser curvature, and diffuse cancer infiltration over ulcer surface to serous membrane. The tumor was diagnosed histologically as adenocarcinoma tabulare mucocellulare."}
{"id": "PMID:191958", "title": "Determination of hydroxylysine in urine.", "content": "A new method for colorimetric determination of urinary hydroxylysine is described. Approximately one-hundredth of human urine collected for 24 hr was diluted to 25 ml and titrated to pH 2.0 with 2  hcl, and then subjected to column chromatography on Dowex 50 X 4 (H+ form). Amino acids were eluted from the column with 1.5 N NH4OH. Hydroxylysine in the elute with 1.5 N NH4OH was separated from the other amino acids, especially from serine and threonine, by preparative paper chromatography. The paper corresponding to hydroxylysine was cut and eluted with water. An aliquot of the eluate with water was oxidized by sodium metaperiodate, and formaldehyde liberated from hydroxylysine was assayed by chromotropic acid reagents, after removing periodate and iodate with Dowex 1 X 8 (formate form). Excretion rate of hydroxylysine in urine of adults was shown to be approximately 110 mumoles per day.", "contents": "Determination of hydroxylysine in urine. A new method for colorimetric determination of urinary hydroxylysine is described. Approximately one-hundredth of human urine collected for 24 hr was diluted to 25 ml and titrated to pH 2.0 with 2  hcl, and then subjected to column chromatography on Dowex 50 X 4 (H+ form). Amino acids were eluted from the column with 1.5 N NH4OH. Hydroxylysine in the elute with 1.5 N NH4OH was separated from the other amino acids, especially from serine and threonine, by preparative paper chromatography. The paper corresponding to hydroxylysine was cut and eluted with water. An aliquot of the eluate with water was oxidized by sodium metaperiodate, and formaldehyde liberated from hydroxylysine was assayed by chromotropic acid reagents, after removing periodate and iodate with Dowex 1 X 8 (formate form). Excretion rate of hydroxylysine in urine of adults was shown to be approximately 110 mumoles per day."}
{"id": "PMID:191959", "title": "Serum angiotensin converting enzyme activity in human bronchial asthma.", "content": "Using hippuryl-L-histidyl-L-leucine as a substrate analog, serum angiotensin converting enzyme (ACE) was spectrophotometrically estimated in patients with bronchial asthma. There were significantly low activities of serum ACE in 115 patients with bronchial asthma irrespective of the presence or absence of acute attack. The activity of serum ACE was reduced more markedly in the chronic type of bronchial asthma than in the paroxysmal type.", "contents": "Serum angiotensin converting enzyme activity in human bronchial asthma. Using hippuryl-L-histidyl-L-leucine as a substrate analog, serum angiotensin converting enzyme (ACE) was spectrophotometrically estimated in patients with bronchial asthma. There were significantly low activities of serum ACE in 115 patients with bronchial asthma irrespective of the presence or absence of acute attack. The activity of serum ACE was reduced more markedly in the chronic type of bronchial asthma than in the paroxysmal type."}
{"id": "PMID:191962", "title": "[2 pools of mitochondria in a single mechanoreceptor neuron].", "content": "The microspectrofluorimetric technique was applied to measure the intracellular ratio of oxidized flavoproteins and NADH in isolated neuron preparation from the stretch receptor organ of the crayfish Astacus leptodactilus. Two pools of mitochondria were detected differing from each other in their functional activity in the single cell at the same time. The mitochondria of the pool are localized near the nucleus, those of the other one being placed along the cell membrane. Physiological treatments (stretch, calcium deficient media) produce different changes in the activity of mitochondria belonging to the different pools. It is suggested that these pools of mitochondria furnish with energy different functional mechanisms within the same cell.", "contents": "[2 pools of mitochondria in a single mechanoreceptor neuron]. The microspectrofluorimetric technique was applied to measure the intracellular ratio of oxidized flavoproteins and NADH in isolated neuron preparation from the stretch receptor organ of the crayfish Astacus leptodactilus. Two pools of mitochondria were detected differing from each other in their functional activity in the single cell at the same time. The mitochondria of the pool are localized near the nucleus, those of the other one being placed along the cell membrane. Physiological treatments (stretch, calcium deficient media) produce different changes in the activity of mitochondria belonging to the different pools. It is suggested that these pools of mitochondria furnish with energy different functional mechanisms within the same cell."}
{"id": "PMID:191961", "title": "Direct evidence for absence of beta-adrenergic receptors in rat cerebral vessels histochemical study with a fluorescent beta-blocker.", "content": "A fluorescent marker for beta-adrenergic receptor sites, 9-amino-acridin propranolol (9-AAP), was administered intravenously to rats. In contrast to other tissues which are known to contain beta-adrenergic receptors, 9-AAP fluorescence was not observed in the walls of the pial as well as parenchymal cerebral vessels. These negative findings strongly suggest that in the rat, beta-adrenergic receptors are not present in the cerebral vasculature. The role of the alpha-adrenergic receptors needs more study.", "contents": "Direct evidence for absence of beta-adrenergic receptors in rat cerebral vessels histochemical study with a fluorescent beta-blocker. A fluorescent marker for beta-adrenergic receptor sites, 9-amino-acridin propranolol (9-AAP), was administered intravenously to rats. In contrast to other tissues which are known to contain beta-adrenergic receptors, 9-AAP fluorescence was not observed in the walls of the pial as well as parenchymal cerebral vessels. These negative findings strongly suggest that in the rat, beta-adrenergic receptors are not present in the cerebral vasculature. The role of the alpha-adrenergic receptors needs more study."}
{"id": "PMID:191966", "title": "Lower motor neuron disease in wild mice caused by indigenous type C virus and search for a similar etiology in human amyotrophic lateral sclerosis.", "content": "In certain genetically susceptible populations of wild mice a progressive motor neuron disease with a long latent period is caused by indigenous type C leukemia virus. Neuronal damage appears to be due primarily to a direct neurotropic effect of the virus and not to an immunogenic mechanism. The disease can be prevented by antiviral genetic means. Search for a similar virus in humans with ALS has been negative.", "contents": "Lower motor neuron disease in wild mice caused by indigenous type C virus and search for a similar etiology in human amyotrophic lateral sclerosis. In certain genetically susceptible populations of wild mice a progressive motor neuron disease with a long latent period is caused by indigenous type C leukemia virus. Neuronal damage appears to be due primarily to a direct neurotropic effect of the virus and not to an immunogenic mechanism. The disease can be prevented by antiviral genetic means. Search for a similar virus in humans with ALS has been negative."}
{"id": "PMID:191968", "title": "[Cholesterol synthesis in the skin of rats with rickets].", "content": "The rachitogenic diet causes an inhibition of cholesterol synthesis in rat skin. Intensity of 2-14S-acetate incorporation into cholesterol precursors (matastenol, lathosterol, 7-dehydrocholesterol) and cholesterol drops considerably. UV-irradiation of animals suffering from rachitis intensifies cholesterol synthesis in skin. Simulteneously an increase is detected in the metabolic fund of cholesterol synthesis precursors, including 7-dehydrocholesterol, which is necessary to form antirachitic compounds in the organism.", "contents": "[Cholesterol synthesis in the skin of rats with rickets]. The rachitogenic diet causes an inhibition of cholesterol synthesis in rat skin. Intensity of 2-14S-acetate incorporation into cholesterol precursors (matastenol, lathosterol, 7-dehydrocholesterol) and cholesterol drops considerably. UV-irradiation of animals suffering from rachitis intensifies cholesterol synthesis in skin. Simulteneously an increase is detected in the metabolic fund of cholesterol synthesis precursors, including 7-dehydrocholesterol, which is necessary to form antirachitic compounds in the organism."}
{"id": "PMID:191969", "title": "[Effect of glucocorticoid hormones on nuclear RNA-polymerase activity and RNA metabolizability in rat skeletal muscles].", "content": "It has been found that in hypercorticism induced by a prolonged ACTH administration when protein synthesis is inhibited in the skeletal muscles the incorporation of Na2HP32O4 into muscle RNA intensifies by 30% and the RNA-polymerase activity of muscle nuclei is approximately twice as high. In the adrenalectomized rats 3 hours after a single hydrocortisone administration a sharp rise in the RNA-polymerase activity of the skeletal muscle nuclei is observed as well. Such an increase in RNA synthesis is suggested to be a response to the inhibition of protein synthesis through feedback mechanisms.", "contents": "[Effect of glucocorticoid hormones on nuclear RNA-polymerase activity and RNA metabolizability in rat skeletal muscles]. It has been found that in hypercorticism induced by a prolonged ACTH administration when protein synthesis is inhibited in the skeletal muscles the incorporation of Na2HP32O4 into muscle RNA intensifies by 30% and the RNA-polymerase activity of muscle nuclei is approximately twice as high. In the adrenalectomized rats 3 hours after a single hydrocortisone administration a sharp rise in the RNA-polymerase activity of the skeletal muscle nuclei is observed as well. Such an increase in RNA synthesis is suggested to be a response to the inhibition of protein synthesis through feedback mechanisms."}
{"id": "PMID:191970", "title": "[Neurochemical mechanisms of the action of tricyclic antidepressants of the imipramine group].", "content": "The main role in determination of the pharmacologic effects of the imipramine groups antidepressants is given to their influence on neurotransmitters metabolism in synapses, the activity of enzymic systems regulating the transport of ions, as well as on the system of cyclic AMP metabolism. Interaction of tricyclic antidepressants with membrane and, as the result, distrubance in reuptake of transmitters (epinephrine and 5-hydroxytryptamine) in neurons is supposed to be one of the mechanisms of synaptic transmission regulation. The possible role in inhibition of biological amines deamination, in particular of phenylethylamine, in antidepressive effect of tricyclic antidepressants is discussed. It is supposed that the thymoanaleptic effects of the imipramine group antidepressants are due to activation of central serotoninergic processes, and their psychoanaleptic effect due to activation of the adrenergic system. Inhibition of the Na+, K+-ATPase activity quilizing effect of tricyclic antidepressants.", "contents": "[Neurochemical mechanisms of the action of tricyclic antidepressants of the imipramine group]. The main role in determination of the pharmacologic effects of the imipramine groups antidepressants is given to their influence on neurotransmitters metabolism in synapses, the activity of enzymic systems regulating the transport of ions, as well as on the system of cyclic AMP metabolism. Interaction of tricyclic antidepressants with membrane and, as the result, distrubance in reuptake of transmitters (epinephrine and 5-hydroxytryptamine) in neurons is supposed to be one of the mechanisms of synaptic transmission regulation. The possible role in inhibition of biological amines deamination, in particular of phenylethylamine, in antidepressive effect of tricyclic antidepressants is discussed. It is supposed that the thymoanaleptic effects of the imipramine group antidepressants are due to activation of central serotoninergic processes, and their psychoanaleptic effect due to activation of the adrenergic system. Inhibition of the Na+, K+-ATPase activity quilizing effect of tricyclic antidepressants."}
{"id": "PMID:191977", "title": "[The effect of newer anthelmintics on Fasciola hepatica in experimentally infected rats].", "content": "The reports deals with the results of testing seven new antihelminthics for Fasciola hepatica in the experimentally invaded Wistar rat. The greatest influence on juvenile flukes (2 and 4 weeks of age) was exerted by diamphenetid (Coriban) applied in a single dose of 100 mg kg-1. Hexachlorophene applied in the dose of 50 mg kg-1 showed the highest effect on sexually mature flukes. All the tested antihelminthics of the halogenated salicylanilide group were ineffective on juvenile stages and only slightly effective on mature F. hepatica flukes. It follows from the results that the effectiveness of some antifasciolics on laboratory animals need not always be in correlation with their effect in ruminants - hence it is necessary to verify the results obtained in laboratory animals and to check them on natural F. hepatica hosts.", "contents": "[The effect of newer anthelmintics on Fasciola hepatica in experimentally infected rats]. The reports deals with the results of testing seven new antihelminthics for Fasciola hepatica in the experimentally invaded Wistar rat. The greatest influence on juvenile flukes (2 and 4 weeks of age) was exerted by diamphenetid (Coriban) applied in a single dose of 100 mg kg-1. Hexachlorophene applied in the dose of 50 mg kg-1 showed the highest effect on sexually mature flukes. All the tested antihelminthics of the halogenated salicylanilide group were ineffective on juvenile stages and only slightly effective on mature F. hepatica flukes. It follows from the results that the effectiveness of some antifasciolics on laboratory animals need not always be in correlation with their effect in ruminants - hence it is necessary to verify the results obtained in laboratory animals and to check them on natural F. hepatica hosts."}
{"id": "PMID:191978", "title": "Experimental induction of feline viral rhinotracheitis virus re-excretion in FVR-recovered cats.", "content": "The re-excretion of feline viral rhinotracheitis (FVR) virus (feline herpesvirus I) by FVR-recovered cats is recorded both spontaneously and following a variety of stimuli, namely, corticosteroid administration, change of housing, and parturition and lactation. At least 27 of 33 (82%) FVR-recovered cats studied were shown to be viral carriers. The carrier state was characterised by periods of viral latency interspersed with episodes of viral shedding. Administration of 0-75 mg dexamethasone trimethylacetate and 2-25 mg prednisolone on days 0,2 and 4 resulted in re-excretion after a mean lag period of 7-2 days in 22 of 32 (69%) FVR-recovered cats on a total of 31 of 57 (54%) occasions. Rehousing resulted in virus re-excretion after a mean lag period of 7-2 days in four of 22 (18%) cats tested on a total of six of 40 (15%) occasions. Apparently spontaneous shedding occurred on a total of 10 occasions in nine of 31 (29%) cats during a mean observation period of 8-8 months. Four of six FVR-recovered queens in a total of four of 10 litters (40%) shed virus within two to 10 weeks of parturition. Serum neutralising antibody titres were generally boosted at the time of first re-infection but afterwards remained essentially constant. Although 82% of cats in these studies were shown to be viral carriers, only 45% of cats shed virus spontaneously or as a result of the natural stress situations and it is postulted that these naturally excreting cats are of most significance epidemiologically.", "contents": "Experimental induction of feline viral rhinotracheitis virus re-excretion in FVR-recovered cats. The re-excretion of feline viral rhinotracheitis (FVR) virus (feline herpesvirus I) by FVR-recovered cats is recorded both spontaneously and following a variety of stimuli, namely, corticosteroid administration, change of housing, and parturition and lactation. At least 27 of 33 (82%) FVR-recovered cats studied were shown to be viral carriers. The carrier state was characterised by periods of viral latency interspersed with episodes of viral shedding. Administration of 0-75 mg dexamethasone trimethylacetate and 2-25 mg prednisolone on days 0,2 and 4 resulted in re-excretion after a mean lag period of 7-2 days in 22 of 32 (69%) FVR-recovered cats on a total of 31 of 57 (54%) occasions. Rehousing resulted in virus re-excretion after a mean lag period of 7-2 days in four of 22 (18%) cats tested on a total of six of 40 (15%) occasions. Apparently spontaneous shedding occurred on a total of 10 occasions in nine of 31 (29%) cats during a mean observation period of 8-8 months. Four of six FVR-recovered queens in a total of four of 10 litters (40%) shed virus within two to 10 weeks of parturition. Serum neutralising antibody titres were generally boosted at the time of first re-infection but afterwards remained essentially constant. Although 82% of cats in these studies were shown to be viral carriers, only 45% of cats shed virus spontaneously or as a result of the natural stress situations and it is postulted that these naturally excreting cats are of most significance epidemiologically."}
{"id": "PMID:191988", "title": "Induction of proliferation in dense non-starved 3T3 cells by Ca++ ionophore A23187.", "content": "The proliferogenic effect of the Ca++ ionophore A23187 was tested in dense non-starved 3T3 cells. Whereas continuous exposure during 48 h of cells to the ionophore at concentrations is larger than or equal to 0.4 muM cytotoxic, a short exposure for 30 s up to 4 min at 0.2 muM was proliferogenic. It was also found that such short exposures to the ionophore caused a transient increase in the intracellular level of cyclic GMP and a roughly simultaneously appearing decrease in the intracellular level of cyclic AMP.", "contents": "Induction of proliferation in dense non-starved 3T3 cells by Ca++ ionophore A23187. The proliferogenic effect of the Ca++ ionophore A23187 was tested in dense non-starved 3T3 cells. Whereas continuous exposure during 48 h of cells to the ionophore at concentrations is larger than or equal to 0.4 muM cytotoxic, a short exposure for 30 s up to 4 min at 0.2 muM was proliferogenic. It was also found that such short exposures to the ionophore caused a transient increase in the intracellular level of cyclic GMP and a roughly simultaneously appearing decrease in the intracellular level of cyclic AMP."}
{"id": "PMID:191989", "title": "Alteration of the cytoplasmic endonuclease cleavage pattern of SV-40 deoxyribonucleic acid in the presence of ATP, actinomycin D and ethidium bromide.", "content": "Endonuclease activities of cytoplasmic extracts of BSC-1 (E1) and BHK-21-cl 13 (E2) cells were assayed with SV-40 as a substrate and analysed by velocity sedimentation in alkaline and neutral sucrose gradients. Endonucleases were found to require Mg2+ ions for their activity. E1 endonuclease generated linear 6 S DNA fragments, pointing to non-random double-strand cleavage of DNA ; the action of E2 endonuclease resulted in double-strand DNA cleavage to fragments heterogeneous in size. Both endonucleases were inhibited by ATP. The inhibitory effect of actinomycin D (AD) was proportional to the AD/DNA molar ratio. AD+ATP association as well as the presence of ethidium bromide altered the cleavage pattern of E1 towards the predominance of single-strand breaks.", "contents": "Alteration of the cytoplasmic endonuclease cleavage pattern of SV-40 deoxyribonucleic acid in the presence of ATP, actinomycin D and ethidium bromide. Endonuclease activities of cytoplasmic extracts of BSC-1 (E1) and BHK-21-cl 13 (E2) cells were assayed with SV-40 as a substrate and analysed by velocity sedimentation in alkaline and neutral sucrose gradients. Endonucleases were found to require Mg2+ ions for their activity. E1 endonuclease generated linear 6 S DNA fragments, pointing to non-random double-strand cleavage of DNA ; the action of E2 endonuclease resulted in double-strand DNA cleavage to fragments heterogeneous in size. Both endonucleases were inhibited by ATP. The inhibitory effect of actinomycin D (AD) was proportional to the AD/DNA molar ratio. AD+ATP association as well as the presence of ethidium bromide altered the cleavage pattern of E1 towards the predominance of single-strand breaks."}
{"id": "PMID:191994", "title": "[Investigations concerning the evidence of herpes simplex virus type 2 (HSV-2) antibodies in patients with carcinoma of the cervix (author's transl)].", "content": "The neutralizing antibodies to HSV-1 and HSV-2 were determined in the sera of 128 patients. Infection was detectable in nearly 100% of the cases in each of the three investigated groups (patients with carcinoma of the cervix, female patients with chronic recurrent HSV infection in the genital area and a control group without and history of HSV infection). The percentage of patients displaying HSV-2 antibodies in the group with carcinoma of the cervix (38%) is significantly higher than in the control group (12%). The results are compared with the findings of other authors and the possible causal significance of HSV in carcinogenesis is discussed.", "contents": "[Investigations concerning the evidence of herpes simplex virus type 2 (HSV-2) antibodies in patients with carcinoma of the cervix (author's transl)]. The neutralizing antibodies to HSV-1 and HSV-2 were determined in the sera of 128 patients. Infection was detectable in nearly 100% of the cases in each of the three investigated groups (patients with carcinoma of the cervix, female patients with chronic recurrent HSV infection in the genital area and a control group without and history of HSV infection). The percentage of patients displaying HSV-2 antibodies in the group with carcinoma of the cervix (38%) is significantly higher than in the control group (12%). The results are compared with the findings of other authors and the possible causal significance of HSV in carcinogenesis is discussed."}
{"id": "PMID:191990", "title": "Fluorometric determination of the quality of FITC conjugates.", "content": "A fluorometric method for the evaluation of FITC conjugates is described. By this method, the titer and the dilution required for complete antigen detection can be determined and an objective comparison of the various conjugate specimens is possible.", "contents": "Fluorometric determination of the quality of FITC conjugates. A fluorometric method for the evaluation of FITC conjugates is described. By this method, the titer and the dilution required for complete antigen detection can be determined and an objective comparison of the various conjugate specimens is possible."}
{"id": "PMID:191991", "title": "[Identification of the optimal requirement of growing animals for polyunsaturated fatty acids].", "content": "Data obtained from studying eight groups of animals of a growing age showed their food rations to ensure proper growth and development when they contain optimal amounts of all food ingredients, including polyunsaturated fatty acids. Therefore, the fatty component in the food rations of test animals should contain both animal and vegetable fats, the latter comprising quantitatively 15 to 25 per cent of diurnal fat allowance. Such an amount of vegetable oil fully provides the rattlings with polyunsaturated fatt acids in a proportion comprising 4.3-5.8 per cent of the diurnal calorific value of the ration. For this reason, in investigations involving animal tests, or experimental substantiation of various problems pertaining to baby alimentation the authors recommend to use in feeding rattlings rations balanced in all the ingredients, including also the fatty acids composition.", "contents": "[Identification of the optimal requirement of growing animals for polyunsaturated fatty acids]. Data obtained from studying eight groups of animals of a growing age showed their food rations to ensure proper growth and development when they contain optimal amounts of all food ingredients, including polyunsaturated fatty acids. Therefore, the fatty component in the food rations of test animals should contain both animal and vegetable fats, the latter comprising quantitatively 15 to 25 per cent of diurnal fat allowance. Such an amount of vegetable oil fully provides the rattlings with polyunsaturated fatt acids in a proportion comprising 4.3-5.8 per cent of the diurnal calorific value of the ration. For this reason, in investigations involving animal tests, or experimental substantiation of various problems pertaining to baby alimentation the authors recommend to use in feeding rattlings rations balanced in all the ingredients, including also the fatty acids composition."}
{"id": "PMID:191992", "title": "[Effect of the nature of the nutrition and of the functional state of the hypophyseal-adrenal system on the \"convulsion readiness\" of the body].", "content": "The effect of some amino acids, succinate and different doses of ACTH on the convulsion response readiness of the organism under the action of a strong sound stimulant was studied. With enrichment of the ration with glutamic acid and also following a parenteral introduction of large doses of succinate a definite protective effect was revealed and, conversely, administration of ACTH (intramuscularly, for 7 day in a dose of 5 Units per 100 g of body weight) increased the convulsion response readiness of the organism. A possible mechanism underlying the detected changes in the convulsion response readiness of the organism under the active factors under study are discussed.", "contents": "[Effect of the nature of the nutrition and of the functional state of the hypophyseal-adrenal system on the \"convulsion readiness\" of the body]. The effect of some amino acids, succinate and different doses of ACTH on the convulsion response readiness of the organism under the action of a strong sound stimulant was studied. With enrichment of the ration with glutamic acid and also following a parenteral introduction of large doses of succinate a definite protective effect was revealed and, conversely, administration of ACTH (intramuscularly, for 7 day in a dose of 5 Units per 100 g of body weight) increased the convulsion response readiness of the organism. A possible mechanism underlying the detected changes in the convulsion response readiness of the organism under the active factors under study are discussed."}
{"id": "PMID:192001", "title": "[Contribution to retrospective roentgenographic follow-up of solitary pulmonary nodules (author's transl)].", "content": "The diagnostic problems of malignant solitary pulmonary nodules are demonstrated in 5 cases with a roentgenographic history of many years. The slow growth rate of adenocarcinoma and alveolar cell carcinoma--mainly in woman--and the possibility of a scar tissue carcinoma has to be considered. Peripheral pulmonary nodules in adult persons suspicious of carcinoma must be verified histologically, even if their growth rate is very slow and their roentgenographic history lasts many years. If this is not possible a thoracotomy should be performed.", "contents": "[Contribution to retrospective roentgenographic follow-up of solitary pulmonary nodules (author's transl)]. The diagnostic problems of malignant solitary pulmonary nodules are demonstrated in 5 cases with a roentgenographic history of many years. The slow growth rate of adenocarcinoma and alveolar cell carcinoma--mainly in woman--and the possibility of a scar tissue carcinoma has to be considered. Peripheral pulmonary nodules in adult persons suspicious of carcinoma must be verified histologically, even if their growth rate is very slow and their roentgenographic history lasts many years. If this is not possible a thoracotomy should be performed."}
{"id": "PMID:192002", "title": "[Main signs of neurologic disease during pregnancy (author's transl)].", "content": "The most important neurologic diseases which may start during pregnancy are described. On the basis of clinical, easily discovered, signs the essential differential diagnosis and specific diagnostic techniques (electromyography, electroneurography, angiography, computotumography) and their indications are outlined. In some detail prognosis and indications for common diseases (epilepsy, M.S.) are discussed. Treatment of those diseases is especially considered in which emergency drug therapy may be needed.", "contents": "[Main signs of neurologic disease during pregnancy (author's transl)]. The most important neurologic diseases which may start during pregnancy are described. On the basis of clinical, easily discovered, signs the essential differential diagnosis and specific diagnostic techniques (electromyography, electroneurography, angiography, computotumography) and their indications are outlined. In some detail prognosis and indications for common diseases (epilepsy, M.S.) are discussed. Treatment of those diseases is especially considered in which emergency drug therapy may be needed."}
{"id": "PMID:191997", "title": "Metabolic fate of N-n-butyl-N-(4-hydroxybutyl)-nitrosamine and its analogues. Selective induction of urinary bladder tumours in the rat.", "content": "1. The metabolic fates of N-n-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and N,N-di-n-butylnitrosamine (DBN) were investigated in the rat and other animal species, to elucidate a possible relationship between metabolism and organotropic carcinogenicity to the urinary bladder of these N-nitrosamines. 2. The principal urinary metabolite of BBN as well as of DBN in the rat was N-n-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), which was demonstrated to be the active form of these compounds as bladder carcinogen. The species difference in response to BBN or DBN is discussed on the basis of the urinary excretion rate of BCPN. 3. Metabolism in vivo and carcinogenicity of a number of BBN analogues were investigated in the rat and a general scheme for biotransformation of N-alkyl-N-(omega-hydroxyalkyl)nitrosamines is given. 4. A possible correlation of structure and metabolism with organotropic carcinogenicity of BBN analogues is discussed, with special reference to selective induction of bladder tumours. 5. A clear demonstration of overlapping carcinogenic and mutagenic activities is presented for BBN, DBN and related compounds.", "contents": "Metabolic fate of N-n-butyl-N-(4-hydroxybutyl)-nitrosamine and its analogues. Selective induction of urinary bladder tumours in the rat. 1. The metabolic fates of N-n-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and N,N-di-n-butylnitrosamine (DBN) were investigated in the rat and other animal species, to elucidate a possible relationship between metabolism and organotropic carcinogenicity to the urinary bladder of these N-nitrosamines. 2. The principal urinary metabolite of BBN as well as of DBN in the rat was N-n-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), which was demonstrated to be the active form of these compounds as bladder carcinogen. The species difference in response to BBN or DBN is discussed on the basis of the urinary excretion rate of BCPN. 3. Metabolism in vivo and carcinogenicity of a number of BBN analogues were investigated in the rat and a general scheme for biotransformation of N-alkyl-N-(omega-hydroxyalkyl)nitrosamines is given. 4. A possible correlation of structure and metabolism with organotropic carcinogenicity of BBN analogues is discussed, with special reference to selective induction of bladder tumours. 5. A clear demonstration of overlapping carcinogenic and mutagenic activities is presented for BBN, DBN and related compounds."}
{"id": "PMID:191998", "title": "Endocrine dysfunction and slipped captial femoral epiphysis.", "content": "Five patients with concomitant endocrinopathy and slipped capital femoral epiphysis were studied in detail. One had diabetes and hypothyroidism, one had hypothyroidism, one had hypergonadotropic hypogonadism and two had a craniopharyngioma (one of whom had severe panhypopituitarism post-operatively). An additional seven patients with cranio-pharyngioma revealed marked delay in closure of epiphyses and an additional undiagnosed case of slipped capital femoral epiphysis. Of the six patients with slipped capital femoral epiphysis, three had bilateral and three unilateral involvement. Of the five patients undergoing surgical stabilization, there was significant delay of epiphyseodesis, prompting us to recommend concomitant bone grafting. Histological examination of the femoral head from a three year old child with panhypopituitarism showed marked irregularity of the growth plate and loss of columnar integrity, which may be a predisposing factor to slipping in older children with endocrinopathies. The effects of various hormones on the physis are specifically discussed, especially as they relate to the possible etiology of slipped capital femoral epiphysis.", "contents": "Endocrine dysfunction and slipped captial femoral epiphysis. Five patients with concomitant endocrinopathy and slipped capital femoral epiphysis were studied in detail. One had diabetes and hypothyroidism, one had hypothyroidism, one had hypergonadotropic hypogonadism and two had a craniopharyngioma (one of whom had severe panhypopituitarism post-operatively). An additional seven patients with cranio-pharyngioma revealed marked delay in closure of epiphyses and an additional undiagnosed case of slipped capital femoral epiphysis. Of the six patients with slipped capital femoral epiphysis, three had bilateral and three unilateral involvement. Of the five patients undergoing surgical stabilization, there was significant delay of epiphyseodesis, prompting us to recommend concomitant bone grafting. Histological examination of the femoral head from a three year old child with panhypopituitarism showed marked irregularity of the growth plate and loss of columnar integrity, which may be a predisposing factor to slipping in older children with endocrinopathies. The effects of various hormones on the physis are specifically discussed, especially as they relate to the possible etiology of slipped capital femoral epiphysis."}
{"id": "PMID:192004", "title": "FORMATION OF H-addition radicals in adenine derivatives: part II.", "content": "The formation of H-addition radicals in monocrystals of adenosine, adenosine-HCl, adenine-HCl-1/2H2O, and adenine-2 HCl by X-irradiation has been st-died by using electron spin resonance spectroscopy at 9.5 GHz and at 35 GHz. In all crystals, both H-addition radicals at position C2 and at position C8 were observed. The coupling constants of these two H-addition radicals are different and depend strongly on the protonation state of the adenine base. INDO calculations reproduce well the observed trends of the coupling constants. It is shown that the C2-addition radical is transformed into the C8-addition radical by heat and vice versa the C8-addition into the C2-addition by light of lambda greater than 360 nm.", "contents": "FORMATION OF H-addition radicals in adenine derivatives: part II. The formation of H-addition radicals in monocrystals of adenosine, adenosine-HCl, adenine-HCl-1/2H2O, and adenine-2 HCl by X-irradiation has been st-died by using electron spin resonance spectroscopy at 9.5 GHz and at 35 GHz. In all crystals, both H-addition radicals at position C2 and at position C8 were observed. The coupling constants of these two H-addition radicals are different and depend strongly on the protonation state of the adenine base. INDO calculations reproduce well the observed trends of the coupling constants. It is shown that the C2-addition radical is transformed into the C8-addition radical by heat and vice versa the C8-addition into the C2-addition by light of lambda greater than 360 nm."}
{"id": "PMID:192005", "title": "Prophage induction by alkylating ethyl methylaminosulfonate.", "content": "Treatment of the lysogenic strain M. lysodeikticus 53-40 (N5) with ethyl methylaminosulfonate results in a slight increase in infective center concentration of N5 phages which is only detectable once disturbing cells had been eliminated by lysozyme. After conversion of ethyl methylaminosulfonate with radioactive labelled guanosine at 37 degrees C, N7-ethyl-guanine could be ascertained. Therefore the biological activity of the drug may be due to an ethylation of DNA.", "contents": "Prophage induction by alkylating ethyl methylaminosulfonate. Treatment of the lysogenic strain M. lysodeikticus 53-40 (N5) with ethyl methylaminosulfonate results in a slight increase in infective center concentration of N5 phages which is only detectable once disturbing cells had been eliminated by lysozyme. After conversion of ethyl methylaminosulfonate with radioactive labelled guanosine at 37 degrees C, N7-ethyl-guanine could be ascertained. Therefore the biological activity of the drug may be due to an ethylation of DNA."}
{"id": "PMID:192006", "title": "[Modification of glyceraldehyde-3-phosphate dehydrogenase from rabbit skeletal muscle by [3-(3-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate (author's transl)].", "content": "The NAD analogue [3-(3-acetylpyridinio)-propyl]adenosine pyrophosphate forms enzymically inactive complexes with glyceraldehyde-3-phosphate dehydrogemase from yeast and rabbit skeletal muscle. In the latter enzyme four mol of the analogue are bound with equal affinity inhibiting the enzyme in a competitive way: K1 = 0.0 mM as compared to the dissociation constant KD = 0.6 mM. The brominated derivative [3-(3-bromoacetylpyridinio)-propyl]adenosine pyrophosphate is covalently bound to both enzymes causing irreversible loss of enzymic activity. Complete inactivation of the enzyme from muscle required two moles of the analogue per mol of tetramer. The remaining two sites are still able to bind two mol of NAD+ without regain of enzymic activity. In the case of the yeast enzyme four mol of the analogue are bound. Inactivation of the rabbit muscle enzyme is accompanied by the disappearance of two out of four highly reactive sulfhydryl groups; in the yeast enzyme the four active site cysteine residues are still able to react with DTNB, the reactivity being diminished significantly. Hybrid formation between the native enzymes from yeast and skeletal muscle is not affected by the modification of the enzyme. Similarly the sedimentation properties of the covalently modified enzyme are indistinguishable from those of the native molecule. This indicates that both the native and the irreversibly inhibited enzyme are identical regarding their quaternary structure.", "contents": "[Modification of glyceraldehyde-3-phosphate dehydrogenase from rabbit skeletal muscle by [3-(3-bromoacetylpyridinio)-propyl]-adenosine pyrophosphate (author's transl)]. The NAD analogue [3-(3-acetylpyridinio)-propyl]adenosine pyrophosphate forms enzymically inactive complexes with glyceraldehyde-3-phosphate dehydrogemase from yeast and rabbit skeletal muscle. In the latter enzyme four mol of the analogue are bound with equal affinity inhibiting the enzyme in a competitive way: K1 = 0.0 mM as compared to the dissociation constant KD = 0.6 mM. The brominated derivative [3-(3-bromoacetylpyridinio)-propyl]adenosine pyrophosphate is covalently bound to both enzymes causing irreversible loss of enzymic activity. Complete inactivation of the enzyme from muscle required two moles of the analogue per mol of tetramer. The remaining two sites are still able to bind two mol of NAD+ without regain of enzymic activity. In the case of the yeast enzyme four mol of the analogue are bound. Inactivation of the rabbit muscle enzyme is accompanied by the disappearance of two out of four highly reactive sulfhydryl groups; in the yeast enzyme the four active site cysteine residues are still able to react with DTNB, the reactivity being diminished significantly. Hybrid formation between the native enzymes from yeast and skeletal muscle is not affected by the modification of the enzyme. Similarly the sedimentation properties of the covalently modified enzyme are indistinguishable from those of the native molecule. This indicates that both the native and the irreversibly inhibited enzyme are identical regarding their quaternary structure."}
{"id": "PMID:192018", "title": "[Paraneoplastic hypoglycemia due to malignant histiocytoma (Doege-Potter syndrome) (author's transl)].", "content": "A case report is given on a male patient who was 52 years old when he died. 9 years ago a nephrectomy was performed because of a densely-packed mesenchymal tumor of the adipose tissue of the pelvis renalis. 7 years after the surgical intervention he suffered from several hypoglycemic crises. An operation was performed, and 2 large tumor nodes were removed from the greater omentum. A retroperitoneal relapse was inoperable. Nevertheless, the disorder of the carbohydrate metabolism disappeared after the operation. At the autopsy, one year later, a large retroperitoneal tumor with metastases in the lymph nodes was found. The neoplastic growth was classified as a malignant histiocytoma, and the hyperglycemia was taken as a paraneoplastic syndrome (Doege-Potter).", "contents": "[Paraneoplastic hypoglycemia due to malignant histiocytoma (Doege-Potter syndrome) (author's transl)]. A case report is given on a male patient who was 52 years old when he died. 9 years ago a nephrectomy was performed because of a densely-packed mesenchymal tumor of the adipose tissue of the pelvis renalis. 7 years after the surgical intervention he suffered from several hypoglycemic crises. An operation was performed, and 2 large tumor nodes were removed from the greater omentum. A retroperitoneal relapse was inoperable. Nevertheless, the disorder of the carbohydrate metabolism disappeared after the operation. At the autopsy, one year later, a large retroperitoneal tumor with metastases in the lymph nodes was found. The neoplastic growth was classified as a malignant histiocytoma, and the hyperglycemia was taken as a paraneoplastic syndrome (Doege-Potter)."}
{"id": "PMID:192019", "title": "[The biological behaviour of experimental tumours of the central nervous system (author's transl)].", "content": "In 31 experimental groups, 1955 rats were exposed to methyl-, dimethyl-, trimethyl-, and ethylnitrosourea or dimethylphenyltriazene. Altogether, 3102 tumours were registered. 1930 of them were located in the central nervous system. Derived from neurooncological classifications in man, these tumours were subdivided corresponding to a three-step grading scheme. In contrast to brain tumours in man, in rats the degree of dedifferentiation is of minor importance with regard to the clinical course of the cancer disease. In rats CNS tumours lead to death of the animals within a few hours or days after the onset of clinical symptomatology and should be regarded as biologically highly malignant. The grading allows a more exact valuation of the frequency of distinct tumour types in different experimental groups. Following transplacental application, isomorphous neoplasms occur significantly more frequent as compared with anisomorphous ones (grad II and III) which dominate when the carcinogen is given repeatedly to adult animals. Parallels are drawn to human neurooncology.", "contents": "[The biological behaviour of experimental tumours of the central nervous system (author's transl)]. In 31 experimental groups, 1955 rats were exposed to methyl-, dimethyl-, trimethyl-, and ethylnitrosourea or dimethylphenyltriazene. Altogether, 3102 tumours were registered. 1930 of them were located in the central nervous system. Derived from neurooncological classifications in man, these tumours were subdivided corresponding to a three-step grading scheme. In contrast to brain tumours in man, in rats the degree of dedifferentiation is of minor importance with regard to the clinical course of the cancer disease. In rats CNS tumours lead to death of the animals within a few hours or days after the onset of clinical symptomatology and should be regarded as biologically highly malignant. The grading allows a more exact valuation of the frequency of distinct tumour types in different experimental groups. Following transplacental application, isomorphous neoplasms occur significantly more frequent as compared with anisomorphous ones (grad II and III) which dominate when the carcinogen is given repeatedly to adult animals. Parallels are drawn to human neurooncology."}
{"id": "PMID:192020", "title": "[Transplacental carcinogenic action of diethylnitrosamine in the Dzungarian hamster (author's transl)].", "content": "After transplacental application (30 mg/kg i.p., 3 days until 6 hours a. p.), diethylnitrosamine induces a high rate (76.2 per cent) of bronchiolar tumours in the lung of the Dzungarian hamster. These tumours were classified as papillary or tubulous adenomas and carcinomas. Furthermore, eome tumours were observed in other organs. The problem of organotropism of diethylnitrosamine, especially among different hamster hamster species, is discussed.", "contents": "[Transplacental carcinogenic action of diethylnitrosamine in the Dzungarian hamster (author's transl)]. After transplacental application (30 mg/kg i.p., 3 days until 6 hours a. p.), diethylnitrosamine induces a high rate (76.2 per cent) of bronchiolar tumours in the lung of the Dzungarian hamster. These tumours were classified as papillary or tubulous adenomas and carcinomas. Furthermore, eome tumours were observed in other organs. The problem of organotropism of diethylnitrosamine, especially among different hamster hamster species, is discussed."}
{"id": "PMID:192021", "title": "[Histological diagnosis and differential diagnosis of localized alveolar cell carcinoma (author's transl)].", "content": "The diagnosis of the alveolar cell carcinoma is based on the fact that it is a cytological and histological highly differentiated tumour. It consists thoroughly out of cylindrical cells. Furthermore, a diffuse carcinosis of the alveoli has to exist, i. e. lining of the intact alveolar walls by cancer cells. The adenocarcinoma is the only alternative in differential diagnosis to the alveolar cell carcinoma in view of the cytological and histological criteria. Pulmonary metastases of extrapulmonary adenocarcinomas can exactly imitate the histologic pattern of the alveolar cell carcinoma and can be diagnosed only by the clinician.", "contents": "[Histological diagnosis and differential diagnosis of localized alveolar cell carcinoma (author's transl)]. The diagnosis of the alveolar cell carcinoma is based on the fact that it is a cytological and histological highly differentiated tumour. It consists thoroughly out of cylindrical cells. Furthermore, a diffuse carcinosis of the alveoli has to exist, i. e. lining of the intact alveolar walls by cancer cells. The adenocarcinoma is the only alternative in differential diagnosis to the alveolar cell carcinoma in view of the cytological and histological criteria. Pulmonary metastases of extrapulmonary adenocarcinomas can exactly imitate the histologic pattern of the alveolar cell carcinoma and can be diagnosed only by the clinician."}
{"id": "PMID:192022", "title": "[Disturbances of sexual function following rectal excision and sphincter preserving resections of the rectum (author's transl)].", "content": "Male sexual function represents a many-sided effect. The disturbances aredeveloped in variable degress. Impotency after excision of malignant tumours occurs in each second patient and after anterior resection is in a third of patients observed. A modest chance for recovery is possible. Careful anatomic dissection is of utmost importance to safe guard the sexual function following curative excision of cancer. This way is less likely to cause injury to the nerves in the critical areas.", "contents": "[Disturbances of sexual function following rectal excision and sphincter preserving resections of the rectum (author's transl)]. Male sexual function represents a many-sided effect. The disturbances aredeveloped in variable degress. Impotency after excision of malignant tumours occurs in each second patient and after anterior resection is in a third of patients observed. A modest chance for recovery is possible. Careful anatomic dissection is of utmost importance to safe guard the sexual function following curative excision of cancer. This way is less likely to cause injury to the nerves in the critical areas."}
{"id": "PMID:192023", "title": "Pig kidney phosphofructokinase. Purification to homogeneity and qualitative basic characterization.", "content": "Phosphofructokinase has been purified from pig kidney by extraction with phosphate buffer at pH 8, followed by alcohol treatment, affinity chromatography on matrix-bound Cibacron blue F3G-A, and gel chromatography on Sepharose 6B. Using sodium dodecyl sulphate electrophoresis the enzyme was found to be homogeneous and to have a specific activity of about 80 units/mg protein. Like other phosphofructokinases, at pH 7.0 the enzyme exhibits a sigmoidal dependence in its activity on the fructose 6-phosphate concentration and is strongly inhibited by ATP. The degree of citrate inhibition is influenced by the concentration of the two substrates. ATP strengthens and fructose 6-phosphate relieves the inhibition by citrate. AMP and cAMP are able to overcome the ATP inhibition. The ADP activation curve is biphasic. The molecular weight of the subunit of pig kidney phosphofructokinase was determined to be 88 000 by means of sodium dodecyl sulphate electrophoresis.", "contents": "Pig kidney phosphofructokinase. Purification to homogeneity and qualitative basic characterization. Phosphofructokinase has been purified from pig kidney by extraction with phosphate buffer at pH 8, followed by alcohol treatment, affinity chromatography on matrix-bound Cibacron blue F3G-A, and gel chromatography on Sepharose 6B. Using sodium dodecyl sulphate electrophoresis the enzyme was found to be homogeneous and to have a specific activity of about 80 units/mg protein. Like other phosphofructokinases, at pH 7.0 the enzyme exhibits a sigmoidal dependence in its activity on the fructose 6-phosphate concentration and is strongly inhibited by ATP. The degree of citrate inhibition is influenced by the concentration of the two substrates. ATP strengthens and fructose 6-phosphate relieves the inhibition by citrate. AMP and cAMP are able to overcome the ATP inhibition. The ADP activation curve is biphasic. The molecular weight of the subunit of pig kidney phosphofructokinase was determined to be 88 000 by means of sodium dodecyl sulphate electrophoresis."}
{"id": "PMID:192025", "title": "Mitochondrial redox components of human adrenocortical steroid hydroxylases under physiological conditions and in focal hyperplasia of the zone fasciculata.", "content": "Cytochrome P450, aa3 and adrenodoxin were characterized in human adrenocortical mitochondria. Human adrenodoxin demonstrated a distinctive electron paramagnetic spectrum exhibiting anisotropic g values indicative of axial symmetry. The observed g values were (formula: see text). Adrenodoxin content of crude human adrenal mitochondria was 0.65 +/- 0.01 nmol/mg of mitochondrial protein and was in a stoichiometric 1:1 molar ration with cytochrome P450. Mitochondrial cytochrome P450 (0.62 nmol/mg mitochondrial protein) and aa3 (0.19 nmol/mg mitochondrial protein) levels were determined in a normal human adrenal A patient receiving ACTH (3d) demonstrated a doubling of P450 content, while cytochrome aa3 levels remained unchanged. ACTH plus hydrocortisone therapy (3d) increased both P450 and aa3 levels, however 24 h hydrocortisone therapy alone was without effect. An area of focal hyperplasia of the zona fasciculata also demonstrated P450 and aa3 levels elevated above the contralateral and normal human adrenal levels. The possibility of hormonal control of human adrenal mitochondrial cytochromes P450 and aa3 is suggested.", "contents": "Mitochondrial redox components of human adrenocortical steroid hydroxylases under physiological conditions and in focal hyperplasia of the zone fasciculata. Cytochrome P450, aa3 and adrenodoxin were characterized in human adrenocortical mitochondria. Human adrenodoxin demonstrated a distinctive electron paramagnetic spectrum exhibiting anisotropic g values indicative of axial symmetry. The observed g values were (formula: see text). Adrenodoxin content of crude human adrenal mitochondria was 0.65 +/- 0.01 nmol/mg of mitochondrial protein and was in a stoichiometric 1:1 molar ration with cytochrome P450. Mitochondrial cytochrome P450 (0.62 nmol/mg mitochondrial protein) and aa3 (0.19 nmol/mg mitochondrial protein) levels were determined in a normal human adrenal A patient receiving ACTH (3d) demonstrated a doubling of P450 content, while cytochrome aa3 levels remained unchanged. ACTH plus hydrocortisone therapy (3d) increased both P450 and aa3 levels, however 24 h hydrocortisone therapy alone was without effect. An area of focal hyperplasia of the zona fasciculata also demonstrated P450 and aa3 levels elevated above the contralateral and normal human adrenal levels. The possibility of hormonal control of human adrenal mitochondrial cytochromes P450 and aa3 is suggested."}
{"id": "PMID:192027", "title": "Biopsy study of hepatocarcinomas in Nigerian Igbos.", "content": "Fifty-five hepatocarcinomas were found in a review of approximately 7,500 surgical biopsies done on Nigerian Igbos during a period of 6 years. The male: female ratio was 2.9:1 and the age peak was between 20 and 49 years. The main symptoms were abdominal swelling, pain, emaciation, jaundice, fever, anorexia and diarrhea. Physical examination revealed a palpable liver in nearly all patients. Two patients presented acutely with hemoperitoneum due to rupture of necrotic tumor nodule. Cirrhosis was found in 60% of the adequately sized specimens. In comparison with published data, this series from an ethnic group in Nigeria, West Africa, reveals both similarities and dissimilarities which are noteworthy.", "contents": "Biopsy study of hepatocarcinomas in Nigerian Igbos. Fifty-five hepatocarcinomas were found in a review of approximately 7,500 surgical biopsies done on Nigerian Igbos during a period of 6 years. The male: female ratio was 2.9:1 and the age peak was between 20 and 49 years. The main symptoms were abdominal swelling, pain, emaciation, jaundice, fever, anorexia and diarrhea. Physical examination revealed a palpable liver in nearly all patients. Two patients presented acutely with hemoperitoneum due to rupture of necrotic tumor nodule. Cirrhosis was found in 60% of the adequately sized specimens. In comparison with published data, this series from an ethnic group in Nigeria, West Africa, reveals both similarities and dissimilarities which are noteworthy."}
{"id": "PMID:192028", "title": "Anti-HBc titer in relation to the etiological role of hepatitis B virus in primary hepatocellular carcinoma.", "content": "The antibody to hepatitis B core antigen (anti-HBc) is belived to be a marker for natural infection with hepatitis B virus (HBV). In order to study the etiological role of HBV in relation to primary hepatocellular carcinoma (PHC), the anti-HBc in sera of 31 PHC patients was surveyed by the immune adherence hemagglutination method which was about 10 times more sensitive than the complement fixation method. Twenty two out of 31 PHC cases were positive for anti-HBc (71.0%). The is a higher rate of incidence than that of HBs-Ag (51.6%). However, high anti-HBc titer above 2(10) which might reflect current infection with HBV was observed in 15 of these 22 cases. The remaining 7 cases had a titer lower than 2(8); 5 of these patients had neither HBs-Ag nor anti-HBs in their sera. As control, 37 anti-HBs positive blood donors with no definite liver disease were surveyed for anti-HBc titer. Thirty-four of them were positive, but in the majority of cases, the serum titer was less than 2(9), which might only reflect previous infection with HBV. These findings indicate that not only the prevalence of anti-HBc, but also the determination of its real titer is quite important for studying the relationship of HBV to PHC.", "contents": "Anti-HBc titer in relation to the etiological role of hepatitis B virus in primary hepatocellular carcinoma. The antibody to hepatitis B core antigen (anti-HBc) is belived to be a marker for natural infection with hepatitis B virus (HBV). In order to study the etiological role of HBV in relation to primary hepatocellular carcinoma (PHC), the anti-HBc in sera of 31 PHC patients was surveyed by the immune adherence hemagglutination method which was about 10 times more sensitive than the complement fixation method. Twenty two out of 31 PHC cases were positive for anti-HBc (71.0%). The is a higher rate of incidence than that of HBs-Ag (51.6%). However, high anti-HBc titer above 2(10) which might reflect current infection with HBV was observed in 15 of these 22 cases. The remaining 7 cases had a titer lower than 2(8); 5 of these patients had neither HBs-Ag nor anti-HBs in their sera. As control, 37 anti-HBs positive blood donors with no definite liver disease were surveyed for anti-HBc titer. Thirty-four of them were positive, but in the majority of cases, the serum titer was less than 2(9), which might only reflect previous infection with HBV. These findings indicate that not only the prevalence of anti-HBc, but also the determination of its real titer is quite important for studying the relationship of HBV to PHC."}
{"id": "PMID:192029", "title": "Postmenopausal osteoporosis: the effect of parathormone and large dose vitamin D3 on the serum calcium level in sex hormone deficient rats.", "content": "Rats deprived of adrenal and gonadel sex hormones are more sensitive than normal rats to the hypercalcaemic (osteolytic) effect of parathormone and toxic doses of vitamin D3. It is suggested that sex hormone deficiency and the consecutive decrease of calcitonin sensitivity in postmenopausal osteoporosis makes the patients unprotected against factors inducing increased bone resorption, and this leads over the years of osteoporosis.", "contents": "Postmenopausal osteoporosis: the effect of parathormone and large dose vitamin D3 on the serum calcium level in sex hormone deficient rats. Rats deprived of adrenal and gonadel sex hormones are more sensitive than normal rats to the hypercalcaemic (osteolytic) effect of parathormone and toxic doses of vitamin D3. It is suggested that sex hormone deficiency and the consecutive decrease of calcitonin sensitivity in postmenopausal osteoporosis makes the patients unprotected against factors inducing increased bone resorption, and this leads over the years of osteoporosis."}
{"id": "PMID:192030", "title": "Role of prostaglandin E2 in the stimulatory effect of ACTH on ovarian blood flow.", "content": "It has been studied in dogs anaesthetized with chloralose-urethane whether Prostaglandin E2(PGE2) might act as a mediator of the stimulatory effect of ACTH on ovarian blood flow. Without any damage to the ovarian vessels, a heated thermocouple was inserted into the stroma of the ovaries and local blood flow was recorded continuously. Similarly to ACTH, PGE2 (100 ng/kg/min) infused into the ovarian bursa increased local blood flow. The ovaries were isolated in situ and perfused by a peristaltic pump from the femoral artery. Synthetic ACTH or PGE2 was infused into the ovarian artery for 15 min and perfusion pressure was measured. Both ACTH (12.5--25.0--50.0--100.0 ng/kg/min) and PGE2 (3912--6.25--12.50--25.00 ng/kg/min) reduced perfusion pressure, caused vasodilatation. There was a significant linear correlation between the degree of vasodilatation and the logarithm of the doses. If the doses of the two agents are expressed in terms of mols, the effect of both agents can be characterized by a common equation. Fifty--200 mug/kg indomethacin inhibited the effect of ACTH but increased the effect of PGE2. It is suggested that in dogs ACTH exerts its ovarian blood flow stimulatory effect by releasing PGE2 or some similar agent(s).", "contents": "Role of prostaglandin E2 in the stimulatory effect of ACTH on ovarian blood flow. It has been studied in dogs anaesthetized with chloralose-urethane whether Prostaglandin E2(PGE2) might act as a mediator of the stimulatory effect of ACTH on ovarian blood flow. Without any damage to the ovarian vessels, a heated thermocouple was inserted into the stroma of the ovaries and local blood flow was recorded continuously. Similarly to ACTH, PGE2 (100 ng/kg/min) infused into the ovarian bursa increased local blood flow. The ovaries were isolated in situ and perfused by a peristaltic pump from the femoral artery. Synthetic ACTH or PGE2 was infused into the ovarian artery for 15 min and perfusion pressure was measured. Both ACTH (12.5--25.0--50.0--100.0 ng/kg/min) and PGE2 (3912--6.25--12.50--25.00 ng/kg/min) reduced perfusion pressure, caused vasodilatation. There was a significant linear correlation between the degree of vasodilatation and the logarithm of the doses. If the doses of the two agents are expressed in terms of mols, the effect of both agents can be characterized by a common equation. Fifty--200 mug/kg indomethacin inhibited the effect of ACTH but increased the effect of PGE2. It is suggested that in dogs ACTH exerts its ovarian blood flow stimulatory effect by releasing PGE2 or some similar agent(s)."}
{"id": "PMID:192031", "title": "Cyclic AMP and segmental epidural analgesia during labour.", "content": "The blood cyclic AMP level was determined just before, during and after induced labour in 27 healthy women. To achieve complete pain relief during the first stage of labour, 14 of them were given segmental epidural analgesia at the height of Th 10-12. The remaining parturients served as controls. Cyclic AMP was above the normal non-gravid level before induction in both groups. In the control group the cyclic AMP content decreased during the first stage of labour, then it increased and reached a peak at the moment of delivery. These changes were, however, not significant. In the epidural group the cyclic AMP level rose significantly during the first stage, and also reached its peak at the moment of delivery. There was a statistically significant difference between the groups at a cervical dilatation of 6-8 cm. After delivery the cyclic AMP rapidly declined to its initial value in both groups. The possible role of the decreased uterine contractions after the block in the increase of the cyclic AMP is discussed.", "contents": "Cyclic AMP and segmental epidural analgesia during labour. The blood cyclic AMP level was determined just before, during and after induced labour in 27 healthy women. To achieve complete pain relief during the first stage of labour, 14 of them were given segmental epidural analgesia at the height of Th 10-12. The remaining parturients served as controls. Cyclic AMP was above the normal non-gravid level before induction in both groups. In the control group the cyclic AMP content decreased during the first stage of labour, then it increased and reached a peak at the moment of delivery. These changes were, however, not significant. In the epidural group the cyclic AMP level rose significantly during the first stage, and also reached its peak at the moment of delivery. There was a statistically significant difference between the groups at a cervical dilatation of 6-8 cm. After delivery the cyclic AMP rapidly declined to its initial value in both groups. The possible role of the decreased uterine contractions after the block in the increase of the cyclic AMP is discussed."}
{"id": "PMID:192033", "title": "Effect of adrenocorticotrophic hormone on muscle acetylcholinesterase and nonspecific esterase.", "content": "Acetylcholinesterases in the muscle homogenates of hamsters receiving ACTH intraperitoneally for six weeks were reduced as compared to the activities in the control samples. In polyacrylamide disc gel electrophoresis of the ACTH-treated muscles some acetylcholinesterase bands were absent. These observations may be significant in explaining the ACTH-induced improvement in myasthenia gravis patients and in the pathophysiology of steroid myopathy.", "contents": "Effect of adrenocorticotrophic hormone on muscle acetylcholinesterase and nonspecific esterase. Acetylcholinesterases in the muscle homogenates of hamsters receiving ACTH intraperitoneally for six weeks were reduced as compared to the activities in the control samples. In polyacrylamide disc gel electrophoresis of the ACTH-treated muscles some acetylcholinesterase bands were absent. These observations may be significant in explaining the ACTH-induced improvement in myasthenia gravis patients and in the pathophysiology of steroid myopathy."}
{"id": "PMID:192034", "title": "In vitro lymphocyte transformation of MS patients to paramyxovirus antigens.", "content": "The immune response of 21 MS patients and 21 healthy volunteers was tested in vitro lymphocyte transformation assay. The stimulating antigens were measles, mumps, parainfluenza, E. coli, S. aureus and C. albicans. MS patients were found to respond similarly to the normal controls to all antigens tested with the exception of mumps antigen. The maximum responses of the MS patients to this antigen were significantly lower than those observed for the normals. However, since 95 per cent of the MS lower maximum responses were still within the positive range, the immunological significance of this phenomenon will require further clarification.", "contents": "In vitro lymphocyte transformation of MS patients to paramyxovirus antigens. The immune response of 21 MS patients and 21 healthy volunteers was tested in vitro lymphocyte transformation assay. The stimulating antigens were measles, mumps, parainfluenza, E. coli, S. aureus and C. albicans. MS patients were found to respond similarly to the normal controls to all antigens tested with the exception of mumps antigen. The maximum responses of the MS patients to this antigen were significantly lower than those observed for the normals. However, since 95 per cent of the MS lower maximum responses were still within the positive range, the immunological significance of this phenomenon will require further clarification."}
{"id": "PMID:192036", "title": "Some histological aspects of amyloid polyneuropathy.", "content": "Two sporadic cases of amyloid polyneuropathy with clinical features corresponding to the Portuguese type of this disease were studied. Histological examination of sural nerve demonstrated a marked loss of myelinated and unmyelinated fibres in the case 1 due to axonal degeneration, high content of fibers with segmental demyelination and the occurrence of several enlarged axons filled with the 10 nm filaments (so-called giant axons). In the case 2 there was total loss of unmyelinated axons and myelinated fibers were nearly completely lacking. In the development of changes in the myelinated fibers their direct compression by amyloid deposits seems to play  an important role. It leads to the appearance of both axonal degeneration and segmental demyelination. The latter seems to be due to local compression and it may involved many fibers. In the  light of observations reported by other authors the mechanism of changes developing in unmuelinated fibers is explained by the presence of changes in the cells of posterior root ganglia, however the question whether some abnormalities seen in unmyelinated axons could not be related to the pressure exerted by amyloid deposits directly to these fibers, remains open.", "contents": "Some histological aspects of amyloid polyneuropathy. Two sporadic cases of amyloid polyneuropathy with clinical features corresponding to the Portuguese type of this disease were studied. Histological examination of sural nerve demonstrated a marked loss of myelinated and unmyelinated fibres in the case 1 due to axonal degeneration, high content of fibers with segmental demyelination and the occurrence of several enlarged axons filled with the 10 nm filaments (so-called giant axons). In the case 2 there was total loss of unmyelinated axons and myelinated fibers were nearly completely lacking. In the development of changes in the myelinated fibers their direct compression by amyloid deposits seems to play  an important role. It leads to the appearance of both axonal degeneration and segmental demyelination. The latter seems to be due to local compression and it may involved many fibers. In the  light of observations reported by other authors the mechanism of changes developing in unmuelinated fibers is explained by the presence of changes in the cells of posterior root ganglia, however the question whether some abnormalities seen in unmyelinated axons could not be related to the pressure exerted by amyloid deposits directly to these fibers, remains open."}
{"id": "PMID:192037", "title": "The ultrastructure of early visna lesions.", "content": "The ultrastructure of visna, a slowly progressive menigo-encephalomyelitis of sheep, was studied in animals sacrificed one month after intracerebral inoculation of visna virus. The major pathological changes, representative of those seen during the first year after infection, consist of inflammation and minor focal destructive lesions of grey and white matter. The inflammatory infiltrates, both subependymal and perivascular as well as of the choroid plexus, were composed mainly of lymphocytes and macrophages with varying numbers of plasma cells. The demyelination seen was of the secondary or Wallerian type. There was no evidence of primary demyelination. Visna virions were not seen in any of the CNS material studied. The ultrastructural findings are compatible with the view that lesions in visna may be induced by a cell-mediated immune response. However, changes characteristic of an autoimmune reaction to myelin antigens were not observed.", "contents": "The ultrastructure of early visna lesions. The ultrastructure of visna, a slowly progressive menigo-encephalomyelitis of sheep, was studied in animals sacrificed one month after intracerebral inoculation of visna virus. The major pathological changes, representative of those seen during the first year after infection, consist of inflammation and minor focal destructive lesions of grey and white matter. The inflammatory infiltrates, both subependymal and perivascular as well as of the choroid plexus, were composed mainly of lymphocytes and macrophages with varying numbers of plasma cells. The demyelination seen was of the secondary or Wallerian type. There was no evidence of primary demyelination. Visna virions were not seen in any of the CNS material studied. The ultrastructural findings are compatible with the view that lesions in visna may be induced by a cell-mediated immune response. However, changes characteristic of an autoimmune reaction to myelin antigens were not observed."}
{"id": "PMID:192038", "title": "Intra-axonal corpora amylacea in the CNS.", "content": "The distribution of intra-axonal corpora amylacea (IACA) in the CNS was studied in 2 cases of ALS, a hepatic encephalopathy and a Shy-Drager syndrome. A total of 149 IACAs were found. IACAs were observed far most frequently in the gracile nuclei, followed by the anterior horns of the spinal cord and in descending order; lateral geniculate bodies, reticular formation, sensory and motor nuclei in the brain stem, cerebellum and cerebral cortex. The basal ganglia, including the thalamus, contained only a few. IACA were not observed in the pyramidal tracts or in the spinal roots. About 3% of the IACA were sectioned longitudinally, together with the original small nerve fibres and abrupt enlargement of the axons due to the deposits was well demonstrated.", "contents": "Intra-axonal corpora amylacea in the CNS. The distribution of intra-axonal corpora amylacea (IACA) in the CNS was studied in 2 cases of ALS, a hepatic encephalopathy and a Shy-Drager syndrome. A total of 149 IACAs were found. IACAs were observed far most frequently in the gracile nuclei, followed by the anterior horns of the spinal cord and in descending order; lateral geniculate bodies, reticular formation, sensory and motor nuclei in the brain stem, cerebellum and cerebral cortex. The basal ganglia, including the thalamus, contained only a few. IACA were not observed in the pyramidal tracts or in the spinal roots. About 3% of the IACA were sectioned longitudinally, together with the original small nerve fibres and abrupt enlargement of the axons due to the deposits was well demonstrated."}
{"id": "PMID:192039", "title": "Light and electron microscopic studies of \"nude\" mice CNS after subcutaneous administration of the E variant of the encephalomyocarditis (EMC) virus.", "content": "Sixteen 3 month old \"nude\" mice, 24 of their litter mates and 30 Swiss mice were injected subcutaneously with 0.1 ml suspension of the E variant of the encephalomyocarditis (EMC) virus. While the mortality rate of the litter mates and Swiss mice during 5-7 days after inoculation was more than 40%, none of the \"nude\" mice died during the experiment. The surviving animals were sacrificed at 24 h intervals from day one to seven days after injection. Brain suspensions assayed for the presence of the virus yielded significant titers at 24 h in all groups, which increased during 7 days. The litter mates and Swiss mice showed proliferation of lymphocytes and microglial cells in the perivascular areas of the brain during the fifth to the seventh day. The  \"nude\" mice, on the other hand, displayed no perivascular lymphocytic infilteration during the same periods. Ultrastructurally, all groups showed aggregates of ribosomes in the cytoplasmic matrix on the third day, which became enlarged in size on the 5th day. At 7 days, both litter mates and Swiss mice showed an increased number of necrotic cells, while these changes were not observed in the \"nude\" mice. These findings suggest that the high mortality rate in immunologically normal mice was related to the efforts of T cells to eliminate virus-infected cells and to produce extensive necrosis, while T cell-depleted animals showed good survival rates.", "contents": "Light and electron microscopic studies of \"nude\" mice CNS after subcutaneous administration of the E variant of the encephalomyocarditis (EMC) virus. Sixteen 3 month old \"nude\" mice, 24 of their litter mates and 30 Swiss mice were injected subcutaneously with 0.1 ml suspension of the E variant of the encephalomyocarditis (EMC) virus. While the mortality rate of the litter mates and Swiss mice during 5-7 days after inoculation was more than 40%, none of the \"nude\" mice died during the experiment. The surviving animals were sacrificed at 24 h intervals from day one to seven days after injection. Brain suspensions assayed for the presence of the virus yielded significant titers at 24 h in all groups, which increased during 7 days. The litter mates and Swiss mice showed proliferation of lymphocytes and microglial cells in the perivascular areas of the brain during the fifth to the seventh day. The  \"nude\" mice, on the other hand, displayed no perivascular lymphocytic infilteration during the same periods. Ultrastructurally, all groups showed aggregates of ribosomes in the cytoplasmic matrix on the third day, which became enlarged in size on the 5th day. At 7 days, both litter mates and Swiss mice showed an increased number of necrotic cells, while these changes were not observed in the \"nude\" mice. These findings suggest that the high mortality rate in immunologically normal mice was related to the efforts of T cells to eliminate virus-infected cells and to produce extensive necrosis, while T cell-depleted animals showed good survival rates."}
{"id": "PMID:192041", "title": "The diagnostic significance of Russell bodies in endoscopic gastric biopsies.", "content": "The incidence of cells containing so-called Russell bodies in 315 benign single gastric biopsies taken from stomachs with proven carcinoma, but outside the carcinomatous area and 786 biopsies taken from stomachs without carcinoma were compared. The Russell body containing cells were counted in a fixed area and on the basis of the counting each biopsy was classified in one of four groups: Russell body containing cells absent or present in a number of 1-5, 6-10 or more than 10 in the area. The results showed that endoscopic biopsy examinations containing one single benign biopsy with more than 5 Russell body containing cells in the carcinoma. If half or more than half of the biopsies in the examination contained 1-5 Russell body containing cells significant differences were also found. The sensitivity of such examinations was low but their predictive values (PVpos) varied from 46 per cent to 95 per cent, meaning that such examinations may be of importance for the diagnosis of gastric cancer.", "contents": "The diagnostic significance of Russell bodies in endoscopic gastric biopsies. The incidence of cells containing so-called Russell bodies in 315 benign single gastric biopsies taken from stomachs with proven carcinoma, but outside the carcinomatous area and 786 biopsies taken from stomachs without carcinoma were compared. The Russell body containing cells were counted in a fixed area and on the basis of the counting each biopsy was classified in one of four groups: Russell body containing cells absent or present in a number of 1-5, 6-10 or more than 10 in the area. The results showed that endoscopic biopsy examinations containing one single benign biopsy with more than 5 Russell body containing cells in the carcinoma. If half or more than half of the biopsies in the examination contained 1-5 Russell body containing cells significant differences were also found. The sensitivity of such examinations was low but their predictive values (PVpos) varied from 46 per cent to 95 per cent, meaning that such examinations may be of importance for the diagnosis of gastric cancer."}
{"id": "PMID:192042", "title": "Relationship between lysosomal damage, fatty infiltration and hepatocellular necrosis in the course of acute liver injury induced by carbon tetrachloride in the rat.", "content": "In the course of liver injury induced by CCl4 in rats the change of the endoplasmic reticulum takes 5 hours and that of the lysosomal membrane, 18 hours to develop. The latter change precedes hepatocellular necrosis. Elevation of plasma free fatty acids and fatty infiltration of the liver can be observed at 3 hours after CCl4 administration. The maximum of fatty infiltration, hepatocellular necrosis and the highest degree of lysosomal damage develop at the same time. Since CCl4 is eliminated in a few hours, it must initiate a cellular process which then leads to lysosomal membrane damage and hepatocellular necrosis.", "contents": "Relationship between lysosomal damage, fatty infiltration and hepatocellular necrosis in the course of acute liver injury induced by carbon tetrachloride in the rat. In the course of liver injury induced by CCl4 in rats the change of the endoplasmic reticulum takes 5 hours and that of the lysosomal membrane, 18 hours to develop. The latter change precedes hepatocellular necrosis. Elevation of plasma free fatty acids and fatty infiltration of the liver can be observed at 3 hours after CCl4 administration. The maximum of fatty infiltration, hepatocellular necrosis and the highest degree of lysosomal damage develop at the same time. Since CCl4 is eliminated in a few hours, it must initiate a cellular process which then leads to lysosomal membrane damage and hepatocellular necrosis."}
{"id": "PMID:192043", "title": "Effect of cyclic adenosine monophosphate on renal function and renin secretion.", "content": "The effect of cAMP, infused into the renal artery, on renal function and on the release of renin was studied in dogs displaying a normal serum Na level. Intrarenal infusion of 1 mg per kg per minute of cAMP caused a significant increase in RBF, dilatation of the efferent arterioles, the redistribution of renal blood flow and a significant increase in tubular Na-reabsorption. The antidiuretic action of cAMP is due partly to a hemodynamic and partly to a direct tubular effect. Decreased renin secretion was explained by the Na-load on the macula densa segment, being decreased by the intrarenal shifting of renal blood flow and with an eventual decomposition of cAMP.", "contents": "Effect of cyclic adenosine monophosphate on renal function and renin secretion. The effect of cAMP, infused into the renal artery, on renal function and on the release of renin was studied in dogs displaying a normal serum Na level. Intrarenal infusion of 1 mg per kg per minute of cAMP caused a significant increase in RBF, dilatation of the efferent arterioles, the redistribution of renal blood flow and a significant increase in tubular Na-reabsorption. The antidiuretic action of cAMP is due partly to a hemodynamic and partly to a direct tubular effect. Decreased renin secretion was explained by the Na-load on the macula densa segment, being decreased by the intrarenal shifting of renal blood flow and with an eventual decomposition of cAMP."}
{"id": "PMID:192046", "title": "Changes in ATP and cyclic nucleotide levels during sympathetic nerve stimulation in canine subcutaneous adipose tissue in situ.", "content": "Subcutaneous adipose tissue in fed, female dogs was isolated. Biopsies of the tissue (30-150 mg) were taken and rapidly frozen in liquid nitrogen before, during and after nerve stimulation (3-4 Hz). In unstimulated adipose tissue the levels of ATP1 were 74+/-7 nmol/g, of cyclic AMP 90 +/- 12 pmol/g and of cyclic PGMP 18 +/- 3 pmol/g (mean+/-S.E.). During sympathetic nerve stimulation the levels of ATP and cyclic GMP fell by 30 and 50% respectively (p less than 0.01), while the cyclic AMP content increased by 50% (p less than 0.05). After nerve stimulation there was a marked increase in glycerol release, and the levels of all three nucleotides returned to control. The fall in ATP during nerve stimulation was essentially eliminated by prior adrenergic alpha-receptor blockade. It is concluded that 1) sympathetic nerve stimulaton induces a rapid, reversible fall in tissue ATP content, which may be related to hypoxia secondary to the vasoconstriction, and 2) lipolytic responses to sympathetic nerve stimulation in vivo are preceeded by small increases in the tissue cyclic AMP level, and a 3-fold increase in the cyclic AMP/cyclic GMP ratio.", "contents": "Changes in ATP and cyclic nucleotide levels during sympathetic nerve stimulation in canine subcutaneous adipose tissue in situ. Subcutaneous adipose tissue in fed, female dogs was isolated. Biopsies of the tissue (30-150 mg) were taken and rapidly frozen in liquid nitrogen before, during and after nerve stimulation (3-4 Hz). In unstimulated adipose tissue the levels of ATP1 were 74+/-7 nmol/g, of cyclic AMP 90 +/- 12 pmol/g and of cyclic PGMP 18 +/- 3 pmol/g (mean+/-S.E.). During sympathetic nerve stimulation the levels of ATP and cyclic GMP fell by 30 and 50% respectively (p less than 0.01), while the cyclic AMP content increased by 50% (p less than 0.05). After nerve stimulation there was a marked increase in glycerol release, and the levels of all three nucleotides returned to control. The fall in ATP during nerve stimulation was essentially eliminated by prior adrenergic alpha-receptor blockade. It is concluded that 1) sympathetic nerve stimulaton induces a rapid, reversible fall in tissue ATP content, which may be related to hypoxia secondary to the vasoconstriction, and 2) lipolytic responses to sympathetic nerve stimulation in vivo are preceeded by small increases in the tissue cyclic AMP level, and a 3-fold increase in the cyclic AMP/cyclic GMP ratio."}
{"id": "PMID:192048", "title": "Family study of high density lipoprotein cholesterol and the relation to age and sex. The Tromso Heart Study.", "content": "A family study of serum high density lipoprotein (HDL) cholesterol and total serum cholesterol concentration has been undertaken, and the relation to age, sex, cigarette smoking, physical activity and familial occurrence of myocardial infarction (MI) was examined. HDL cholesterol was determined in 251 females and 194 males and total serum cholesterol in 677 females and 657 males, all aged 0-49 years. With respect to HDL cholesterol, significant sex differences were observed both in absolute level and in age-related change. A negative correlation between HDL cholesterol and total serum cholesterol was observed in all age groups except females aged 0-19 years, supporting the hypothesis of HDL as a \"\"clearing'' lipoprotein. HDL cholesterol showed a positive correlation only in pairs of first-degree relatives involving the mother and in sib-sib paris of the same sex. On the other hand, for serum cholesterol a positive correlation was found among all family members, although significantly higher between first-degree relatives than between spouses. No relation was found between cigarette smoking, physical activity of familial occurrence of MI and the HDL cholesterol or total serum cholesterol concentrations. In accordance with the \"\"HDL hypothesis'', the present finding could partly explain the higher incidence of ischaemic heart disease (IHD) in males than in females, and partly also the high risk which is transmitted from women with IHD to their first-degree relatives.", "contents": "Family study of high density lipoprotein cholesterol and the relation to age and sex. The Tromso Heart Study. A family study of serum high density lipoprotein (HDL) cholesterol and total serum cholesterol concentration has been undertaken, and the relation to age, sex, cigarette smoking, physical activity and familial occurrence of myocardial infarction (MI) was examined. HDL cholesterol was determined in 251 females and 194 males and total serum cholesterol in 677 females and 657 males, all aged 0-49 years. With respect to HDL cholesterol, significant sex differences were observed both in absolute level and in age-related change. A negative correlation between HDL cholesterol and total serum cholesterol was observed in all age groups except females aged 0-19 years, supporting the hypothesis of HDL as a \"\"clearing'' lipoprotein. HDL cholesterol showed a positive correlation only in pairs of first-degree relatives involving the mother and in sib-sib paris of the same sex. On the other hand, for serum cholesterol a positive correlation was found among all family members, although significantly higher between first-degree relatives than between spouses. No relation was found between cigarette smoking, physical activity of familial occurrence of MI and the HDL cholesterol or total serum cholesterol concentrations. In accordance with the \"\"HDL hypothesis'', the present finding could partly explain the higher incidence of ischaemic heart disease (IHD) in males than in females, and partly also the high risk which is transmitted from women with IHD to their first-degree relatives."}
{"id": "PMID:192049", "title": "Substance P and primary afferent transmission.", "content": "Substance P has a powerful excitant action on spinal motoneurons of the newborn rat, and the action is specifically antagonized by Lioresal, which also readily blocks spinal reflexes involving primary afferent transmission. Substance P is highly concentrated in bovine and feline dorsal roots as well as in the dorsal part of the dorsal horn of cat spinal cord. There is evidence that substance P is synthesized in spinal ganglia, transported through the dorsal roots and stored in the axon terminals of primary afferent neurons. These and other results suggest that the undecapeptide substance P, or one of its shorter C-terminal analogues, functions as an excitatory transmitter of the primary afferent fibers.", "contents": "Substance P and primary afferent transmission. Substance P has a powerful excitant action on spinal motoneurons of the newborn rat, and the action is specifically antagonized by Lioresal, which also readily blocks spinal reflexes involving primary afferent transmission. Substance P is highly concentrated in bovine and feline dorsal roots as well as in the dorsal part of the dorsal horn of cat spinal cord. There is evidence that substance P is synthesized in spinal ganglia, transported through the dorsal roots and stored in the axon terminals of primary afferent neurons. These and other results suggest that the undecapeptide substance P, or one of its shorter C-terminal analogues, functions as an excitatory transmitter of the primary afferent fibers."}
{"id": "PMID:192051", "title": "Changes of rat cerebellar guanosine 3',5'-cyclic phosphate by dopaminergic mechanisms in vivo.", "content": "Apomorphine produced a dose-dependent increase of the cGMP level in the cerebellum. Haloperidol and scopolamine completely prevented this increase, and reserpine reduced the increase to 50%. LSD elevated cerebellar cGMP, and this effect was also abolished by haloperidol. It is suggested that the primary site of action of these drugs is the caudate nucleus, from which two neuronal pathways could trigger the increase of cGMP in the cerebellum.", "contents": "Changes of rat cerebellar guanosine 3',5'-cyclic phosphate by dopaminergic mechanisms in vivo. Apomorphine produced a dose-dependent increase of the cGMP level in the cerebellum. Haloperidol and scopolamine completely prevented this increase, and reserpine reduced the increase to 50%. LSD elevated cerebellar cGMP, and this effect was also abolished by haloperidol. It is suggested that the primary site of action of these drugs is the caudate nucleus, from which two neuronal pathways could trigger the increase of cGMP in the cerebellum."}
{"id": "PMID:192053", "title": "Opiates, cyclic nucleotides, and xanthines.", "content": "In rat brain homogenate, opiates exert a dose-related inhibition of PGE-stimulated cyclic (AMP) formation. This effect is stereospecific and is correlated with agonist potency. Naloxone antagonizes heroid in a dose-related way, without, at effective concentrations, itself inhibiting PGE-stimulated cyclic AMP formation. In morphine-dependent rats, intracerebroventricular injection of cyclic AMP intensifies and of dibutyryl cyclic GMP diminishes precipitated abstinence effects. In naive rats, the xanthines, theophylline and 3-isobutyl-1-methylxanthine, produce a quasimorphine-abstinence syndrome that is readily suppressed by heroin and intensified by nalosone. In rat brain homogenate, these xanthines inhibit cyclic AMP phosphodiesterase. These findings are concistent with these views: (a) The opiates specifically inhibit an adenylate cyclase of morphine-sensitive neurons that is sensitive to stimulation by PGEs. (b) Opiate agonist action is associated with the lowering of a neuronal cyclic AMP. (c) Both the morphine-abstinence syndrome in dependent rats and the quasi-abstinence syndrome in naive rats are associated with a rise in this neuronal cyclic AMP. (d) There are two types of endogenous humoral mediator acting on morphine-sensitive neurons, one of which is morphine-like and the other antimorphine-like in action.", "contents": "Opiates, cyclic nucleotides, and xanthines. In rat brain homogenate, opiates exert a dose-related inhibition of PGE-stimulated cyclic (AMP) formation. This effect is stereospecific and is correlated with agonist potency. Naloxone antagonizes heroid in a dose-related way, without, at effective concentrations, itself inhibiting PGE-stimulated cyclic AMP formation. In morphine-dependent rats, intracerebroventricular injection of cyclic AMP intensifies and of dibutyryl cyclic GMP diminishes precipitated abstinence effects. In naive rats, the xanthines, theophylline and 3-isobutyl-1-methylxanthine, produce a quasimorphine-abstinence syndrome that is readily suppressed by heroin and intensified by nalosone. In rat brain homogenate, these xanthines inhibit cyclic AMP phosphodiesterase. These findings are concistent with these views: (a) The opiates specifically inhibit an adenylate cyclase of morphine-sensitive neurons that is sensitive to stimulation by PGEs. (b) Opiate agonist action is associated with the lowering of a neuronal cyclic AMP. (c) Both the morphine-abstinence syndrome in dependent rats and the quasi-abstinence syndrome in naive rats are associated with a rise in this neuronal cyclic AMP. (d) There are two types of endogenous humoral mediator acting on morphine-sensitive neurons, one of which is morphine-like and the other antimorphine-like in action."}
{"id": "PMID:192054", "title": "Repartition and drug sensitivity of dopamine and L-isoproterenol-sensitive adenylate cyclases in rat brain homogenates.", "content": "The characteristics of dopamine, 1-isoproterenol, and d-LSD stimulated adenylate cyclases were studied in homogenates of fresh or frozen tissues. In rat striatum, when the assay was done in the presence of 1 mM MgSO4, dopamine (10(-4) M) stimulated the enzyme activity by 3.5-fold. This effect was completely blocked by fluphenazine (10(-5) M; Ki = 9 X 10(-9) M) and by phentolamine (Ki = 3 X 10(-7) M). d-LSD stimulated the adenylate cyclase activity (Km = 1.4 X 10(-7) M) by interacting with the dopaminergic receptors. Maximal adenylate cyclase stimulation by d-LSD was 1.4-fold; as a matter of fact, this compound acted as a partial agonist on the dopaminergic receptors. l-Isoproterenol (Km = 10(-6) M) activated an adenylate cyclase present in rat striatum homogenates through a receptor distinct from the dopaminergic receptor; this stimulation was not affected by addition of fluphenazine or phentolamine but suppressed by dl-propranolol (10(-4) M). The topographical distributions of dopamine adenylate cyclase activity and endogeneous dopamine content were examined in homogenates prepared from discs punched out from serial frozen (-7 degrees C) slices of the striatum. A 4.8-fold progressive decrease in the amount of cyclic AMP produced in the presence of dopamine (10(-4) M) was observed from the rostral to the caudal part of the structure. The d-LSD-sensitive adenylate cyclase followed a similar distribution. It should be noted that the topographic distribution of endogeneous dopamine is quite comparable to the distribution of the dopamine-sensitive adenylate cyclase, suggesting that this enzyme is an integral part of the dopamine synapses. We also reported that the frontal cortex contains a dopamine-sensitive adenylate cyclase. In conclusion, we trust that the micromethod described for adenylate cyclase assay will be of some use in the study of the precise topographic distribution of catecholamine sensitive adenylate cyclases in different structures of brain.", "contents": "Repartition and drug sensitivity of dopamine and L-isoproterenol-sensitive adenylate cyclases in rat brain homogenates. The characteristics of dopamine, 1-isoproterenol, and d-LSD stimulated adenylate cyclases were studied in homogenates of fresh or frozen tissues. In rat striatum, when the assay was done in the presence of 1 mM MgSO4, dopamine (10(-4) M) stimulated the enzyme activity by 3.5-fold. This effect was completely blocked by fluphenazine (10(-5) M; Ki = 9 X 10(-9) M) and by phentolamine (Ki = 3 X 10(-7) M). d-LSD stimulated the adenylate cyclase activity (Km = 1.4 X 10(-7) M) by interacting with the dopaminergic receptors. Maximal adenylate cyclase stimulation by d-LSD was 1.4-fold; as a matter of fact, this compound acted as a partial agonist on the dopaminergic receptors. l-Isoproterenol (Km = 10(-6) M) activated an adenylate cyclase present in rat striatum homogenates through a receptor distinct from the dopaminergic receptor; this stimulation was not affected by addition of fluphenazine or phentolamine but suppressed by dl-propranolol (10(-4) M). The topographical distributions of dopamine adenylate cyclase activity and endogeneous dopamine content were examined in homogenates prepared from discs punched out from serial frozen (-7 degrees C) slices of the striatum. A 4.8-fold progressive decrease in the amount of cyclic AMP produced in the presence of dopamine (10(-4) M) was observed from the rostral to the caudal part of the structure. The d-LSD-sensitive adenylate cyclase followed a similar distribution. It should be noted that the topographic distribution of endogeneous dopamine is quite comparable to the distribution of the dopamine-sensitive adenylate cyclase, suggesting that this enzyme is an integral part of the dopamine synapses. We also reported that the frontal cortex contains a dopamine-sensitive adenylate cyclase. In conclusion, we trust that the micromethod described for adenylate cyclase assay will be of some use in the study of the precise topographic distribution of catecholamine sensitive adenylate cyclases in different structures of brain."}
{"id": "PMID:192061", "title": "Translational regulatory mechanisms in neoplasia in vivo.", "content": "It is clear that regulation of genetic expression of cells need not involve alterations of the basic DNA structure. Between the production of messenger RNA and enzyme degradation there are a number of steps, any of which can be modulated by hormones and other factors to yield cellular abnormalities associated with malignancy. It is important to identify the exact step at which a carcinogen operates and to discover how this alteration is transmitted to the progeny of malignant cells.", "contents": "Translational regulatory mechanisms in neoplasia in vivo. It is clear that regulation of genetic expression of cells need not involve alterations of the basic DNA structure. Between the production of messenger RNA and enzyme degradation there are a number of steps, any of which can be modulated by hormones and other factors to yield cellular abnormalities associated with malignancy. It is important to identify the exact step at which a carcinogen operates and to discover how this alteration is transmitted to the progeny of malignant cells."}
{"id": "PMID:192065", "title": "Serum lipids and proteins in lactose malabsorption.", "content": "It has been suggested that dietary lactose may reduce the intestinal absorption of fat and protein in individuals with lactase deficiency. On the other hand, it is known that a high carbohydrate diet increases serum lipids. The purpose of this study was to examine whether there are differences in the fasting serum lipid and protein concentrations between people with lactose malabsorption and people with normal lactose absorption. Therefore in the connection of a family study serum lipids and proteins were measured in 409 subjects belonging to 11 families. Of these 288 were relatives of the 11 index persons and 121 were spouses or relatives of the spouses. The weight, height, and milk consumption of each person were recorded. When the age, sex, relative weight and milk consumption effects were taken into account there was a statistical difference between the lactose malabsorption and lactose absorption groups for the concentration of serum triglycerides, but not for the other variables. Besides, serum triglyceride values of over 200 mg/100 ml were significantly fewer in people with lactose malabsorption. It was hypothesized that increased intestinal motility may disturb the absorption of fats and cause the observed difference at least in the Finnish population.", "contents": "Serum lipids and proteins in lactose malabsorption. It has been suggested that dietary lactose may reduce the intestinal absorption of fat and protein in individuals with lactase deficiency. On the other hand, it is known that a high carbohydrate diet increases serum lipids. The purpose of this study was to examine whether there are differences in the fasting serum lipid and protein concentrations between people with lactose malabsorption and people with normal lactose absorption. Therefore in the connection of a family study serum lipids and proteins were measured in 409 subjects belonging to 11 families. Of these 288 were relatives of the 11 index persons and 121 were spouses or relatives of the spouses. The weight, height, and milk consumption of each person were recorded. When the age, sex, relative weight and milk consumption effects were taken into account there was a statistical difference between the lactose malabsorption and lactose absorption groups for the concentration of serum triglycerides, but not for the other variables. Besides, serum triglyceride values of over 200 mg/100 ml were significantly fewer in people with lactose malabsorption. It was hypothesized that increased intestinal motility may disturb the absorption of fats and cause the observed difference at least in the Finnish population."}
{"id": "PMID:192066", "title": "Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition.", "content": "A white female, now age 40 and receiving total parenteral nutrition for more than 5 years, developed unexpected 15% weight loss after 3 1/2 years of regimen, together with peripheral neuropathy confirmed by nerve conduction measurements. An intravenous glucose tolerance test showed that the fractional rate (K) had decreased to 0.89%/min (normal greater than 1.2). There was observed during this glucose infusion a borderline normal insulin response with a fall in plasma free fatty acids and in plasma leucine. During daily infusion of well over 400 g of glucose, the respiratory quotient was 0.66. Chromium balance was negative. Chromium levels were, in blood 0.55 ng/ml (normal 4.9 to 9.5) and in hair 154 to 175 ng/g (normal greater than 500). Regular insulin daily (45 micron) in the infusate nearly maintained euglycemia but despite this, and even with further glucose intake to restore weight loss, intravenous glucose tolerance test (K) and respiratory quotient were unchanged. Administration of insulin was then stopped and 250 microng of Cr added to the daily total parenteral nutrition infusate for 2 weeks. After this the intravenous glucose tolerance test (K) and respiratory quotient became normal (1.35 and 0.78, respectively). Over the next 5 months insulin was not needed and glucose intake had to be reduced substantially to avoid overweight. In this period nerve conduction and well-being returned to normal. With a maintenance addition of chromium to the total parenteral nutrition infusate (tentatively this addition is 20 microng/day) the patient has remained well for 18 months (to July 1976). These results suggest that relatively isolated chromium deficiency in man, hitherto poorly documented, causes 1) glucose intolerance, 2) inability to utilize glucose for energy, 3) neuropathy with normal insulin levels, 4) high free fatty acid levels and low respiratory quotient and, 5) abnormalities of nitrogen metabolism.", "contents": "Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition. A white female, now age 40 and receiving total parenteral nutrition for more than 5 years, developed unexpected 15% weight loss after 3 1/2 years of regimen, together with peripheral neuropathy confirmed by nerve conduction measurements. An intravenous glucose tolerance test showed that the fractional rate (K) had decreased to 0.89%/min (normal greater than 1.2). There was observed during this glucose infusion a borderline normal insulin response with a fall in plasma free fatty acids and in plasma leucine. During daily infusion of well over 400 g of glucose, the respiratory quotient was 0.66. Chromium balance was negative. Chromium levels were, in blood 0.55 ng/ml (normal 4.9 to 9.5) and in hair 154 to 175 ng/g (normal greater than 500). Regular insulin daily (45 micron) in the infusate nearly maintained euglycemia but despite this, and even with further glucose intake to restore weight loss, intravenous glucose tolerance test (K) and respiratory quotient were unchanged. Administration of insulin was then stopped and 250 microng of Cr added to the daily total parenteral nutrition infusate for 2 weeks. After this the intravenous glucose tolerance test (K) and respiratory quotient became normal (1.35 and 0.78, respectively). Over the next 5 months insulin was not needed and glucose intake had to be reduced substantially to avoid overweight. In this period nerve conduction and well-being returned to normal. With a maintenance addition of chromium to the total parenteral nutrition infusate (tentatively this addition is 20 microng/day) the patient has remained well for 18 months (to July 1976). These results suggest that relatively isolated chromium deficiency in man, hitherto poorly documented, causes 1) glucose intolerance, 2) inability to utilize glucose for energy, 3) neuropathy with normal insulin levels, 4) high free fatty acid levels and low respiratory quotient and, 5) abnormalities of nitrogen metabolism."}
{"id": "PMID:192067", "title": "Effects of dibutyryl cyclic adenosinemonophosphate and prostaglandin E1 on platelet aggregation and shape changes.", "content": "Prostaglandin E1 (PGE1) exerted an immediate inhibitory effect upon the induction of platelet aggregation by adenosinediphosphate, epinephrine, thrombin, bovine fibrinogen, or sodium fluoride, whereas dibutyryl cyclic adenosinemonophosphate (DBcAMP) produced a delayed type of inhibition of aggregation induced by these same agents. In addition, however, both PGE1 and DBcAMP, as well as adenosinetriphosphate (ATP) and Mg++, restored, with incubation, the washed platelets to a more discoid shape. Platelet aggregability also correlated well with platelet shape. All of these findings suggest the possibility of mediation of the delayed type of inhibition through restoration of the platelet membrane by increasing the level of metabolically active ATP or the availability of cations. They tend, however, to exclude the possibility that PGE1 exerts its immediate inhibitory effect through the increase of platelet cAMP.", "contents": "Effects of dibutyryl cyclic adenosinemonophosphate and prostaglandin E1 on platelet aggregation and shape changes. Prostaglandin E1 (PGE1) exerted an immediate inhibitory effect upon the induction of platelet aggregation by adenosinediphosphate, epinephrine, thrombin, bovine fibrinogen, or sodium fluoride, whereas dibutyryl cyclic adenosinemonophosphate (DBcAMP) produced a delayed type of inhibition of aggregation induced by these same agents. In addition, however, both PGE1 and DBcAMP, as well as adenosinetriphosphate (ATP) and Mg++, restored, with incubation, the washed platelets to a more discoid shape. Platelet aggregability also correlated well with platelet shape. All of these findings suggest the possibility of mediation of the delayed type of inhibition through restoration of the platelet membrane by increasing the level of metabolically active ATP or the availability of cations. They tend, however, to exclude the possibility that PGE1 exerts its immediate inhibitory effect through the increase of platelet cAMP."}
{"id": "PMID:192068", "title": "Screening of mammary carcinoma for hormone dependency in vitro. Enzymatic activity in short-term organotypic cultures of breast biopsies from 62 patients.", "content": "Enzymatic activity in short-term organotypic cultures of breast biopsies from 62 patients. Am J Clin Pathol 67: 393-396, 1977. Mammary carcinomas from 62 patients were assessed for pentose shunt dehydrogenase activity initially and after 24-72 hours in organotypic cultures with or without exogenous hormones. Hormones tested were (1) estradiol, (2) testosterone, and (3) prolactin. Thirty-seven (60%) were judged hormone-independent, in vitro; 14 (23%) were judged hormone-dependent, in vitro; 11 (17%) were classed as \"indeterminant.\" Clinical results of endocrine management of 13 cases and an appraisal of the usefulness of the method are presented.", "contents": "Screening of mammary carcinoma for hormone dependency in vitro. Enzymatic activity in short-term organotypic cultures of breast biopsies from 62 patients. Enzymatic activity in short-term organotypic cultures of breast biopsies from 62 patients. Am J Clin Pathol 67: 393-396, 1977. Mammary carcinomas from 62 patients were assessed for pentose shunt dehydrogenase activity initially and after 24-72 hours in organotypic cultures with or without exogenous hormones. Hormones tested were (1) estradiol, (2) testosterone, and (3) prolactin. Thirty-seven (60%) were judged hormone-independent, in vitro; 14 (23%) were judged hormone-dependent, in vitro; 11 (17%) were classed as \"indeterminant.\" Clinical results of endocrine management of 13 cases and an appraisal of the usefulness of the method are presented."}
{"id": "PMID:192069", "title": "Fructose-1,6-diphosphatase deficiency.", "content": "A girl aged 3 years and 11 months, with recurrent episodes of unexplained metabolic acidosis, hepatomegaly, and fasting hypoglycemia unresponsive to glucagon, showed profound falls in blood glucose levels in response to oral fructose and glycerol challenge. In vitro analysis of her hepatic glycolytic and gluconeogenic enzymes demonstrated absent fructose-1,6-diphosphatase activity. A therapeutic trial of orally given folic acid, 30 mg daily, did not improve her tolerance for fructose and glycerol. Over the next two years she showed improvement in tolerance to fasting, and to fructose and glycerol loading on dietary management.", "contents": "Fructose-1,6-diphosphatase deficiency. A girl aged 3 years and 11 months, with recurrent episodes of unexplained metabolic acidosis, hepatomegaly, and fasting hypoglycemia unresponsive to glucagon, showed profound falls in blood glucose levels in response to oral fructose and glycerol challenge. In vitro analysis of her hepatic glycolytic and gluconeogenic enzymes demonstrated absent fructose-1,6-diphosphatase activity. A therapeutic trial of orally given folic acid, 30 mg daily, did not improve her tolerance for fructose and glycerol. Over the next two years she showed improvement in tolerance to fasting, and to fructose and glycerol loading on dietary management."}
{"id": "PMID:192070", "title": "Cholangiocarcinoma associated with biliary cirrhosis due to congenital biliary atresia.", "content": "An 11-year-old girl developed cholangiocellular carcinoma in association with biliary cirrhosis due to congenital biliary atresia. An exploratory laparotomy and an operative cholangiogram at 3 months of age had confirmed the diagnosis of extrahepatic biliary atresia. A liver biopsy specimen taken at 6 months of age showed biliary cirrhosis. The subsequent clinical course was characterized by persistent moderate jaundice, anemia, malnutrition, rickets, pathologic fractures, and recurrent gastrointestinal bleeding. The presence of cholangiocellular carcinoma of the liver with advanced biliary cirrhosis was established at an exploratory laparotomy a week before her death. We discuss here the pathogenesis of biliary cirrhosis and carcinoma of the liver; there may be a relation between the two in the childhood population.", "contents": "Cholangiocarcinoma associated with biliary cirrhosis due to congenital biliary atresia. An 11-year-old girl developed cholangiocellular carcinoma in association with biliary cirrhosis due to congenital biliary atresia. An exploratory laparotomy and an operative cholangiogram at 3 months of age had confirmed the diagnosis of extrahepatic biliary atresia. A liver biopsy specimen taken at 6 months of age showed biliary cirrhosis. The subsequent clinical course was characterized by persistent moderate jaundice, anemia, malnutrition, rickets, pathologic fractures, and recurrent gastrointestinal bleeding. The presence of cholangiocellular carcinoma of the liver with advanced biliary cirrhosis was established at an exploratory laparotomy a week before her death. We discuss here the pathogenesis of biliary cirrhosis and carcinoma of the liver; there may be a relation between the two in the childhood population."}
{"id": "PMID:192071", "title": "Obstructive jaundice secondary to hepatoma. Case report and literature review.", "content": "A 67-year old male, who presented a clinical picture of obstructive jaundice with cholangitis, was found to have hepatoma tumor embolus blocking the common duct. The site of invasion was the right hepatic duct. There are 15 such cases reported in the literature. Hepatoma rarely presents with obstructive jaundice. A clinical picture of biliary colic or cholangitis is frequently misleading. Invasion of a hepatic duct large enough to allow formation of a tumor embolus implies tumor close to the bifurcation of right and left hepatic ducts and has precluded effective surgical treatment in all but one case.", "contents": "Obstructive jaundice secondary to hepatoma. Case report and literature review. A 67-year old male, who presented a clinical picture of obstructive jaundice with cholangitis, was found to have hepatoma tumor embolus blocking the common duct. The site of invasion was the right hepatic duct. There are 15 such cases reported in the literature. Hepatoma rarely presents with obstructive jaundice. A clinical picture of biliary colic or cholangitis is frequently misleading. Invasion of a hepatic duct large enough to allow formation of a tumor embolus implies tumor close to the bifurcation of right and left hepatic ducts and has precluded effective surgical treatment in all but one case."}
{"id": "PMID:192072", "title": "Long-term follow-up studies on herpes simplex antibodies in the course of cervical cancer: patterns of neutralizing antibodies.", "content": "The kinetics of neutralization was used to study antibodies to herpes simplex virus type 2 in 90 patients with invasive carcinoma of the cervix uteri. The first sera were drawn before treatment and consective sera were drawn at intervals thereafter. Control groups consisted of 90 age-matched healthy women and 70 cancer patients suffering from malignancies other than cervix carcinoma. Patients surviving during the observation period of 12-60 months had a significantly higher frequency of neutralizing antibodies than control groups. Twenty-six of the women with cervix carcinoma died during the observation period and 13 others had a recurrence of the cancer. Survivors with advanced cervical cancer had higher antibody titers than survivors with less severe cervical cancer while patients whose cancer caused death had low titer or to a great extent lacked neutralizing antibodies. Women with recurrences and progressing cervical lesions had no detectable antibodies while women with recurrences and regressing lesions all had antibodies. There was a rise in K2-values 6-18 months after treatment. In serum samples collected later than 18 months, there was a return to original levels.", "contents": "Long-term follow-up studies on herpes simplex antibodies in the course of cervical cancer: patterns of neutralizing antibodies. The kinetics of neutralization was used to study antibodies to herpes simplex virus type 2 in 90 patients with invasive carcinoma of the cervix uteri. The first sera were drawn before treatment and consective sera were drawn at intervals thereafter. Control groups consisted of 90 age-matched healthy women and 70 cancer patients suffering from malignancies other than cervix carcinoma. Patients surviving during the observation period of 12-60 months had a significantly higher frequency of neutralizing antibodies than control groups. Twenty-six of the women with cervix carcinoma died during the observation period and 13 others had a recurrence of the cancer. Survivors with advanced cervical cancer had higher antibody titers than survivors with less severe cervical cancer while patients whose cancer caused death had low titer or to a great extent lacked neutralizing antibodies. Women with recurrences and progressing cervical lesions had no detectable antibodies while women with recurrences and regressing lesions all had antibodies. There was a rise in K2-values 6-18 months after treatment. In serum samples collected later than 18 months, there was a return to original levels."}
{"id": "PMID:192073", "title": "The Seattle Virus Watch. VII. Observations of adenovirus infections.", "content": "The following findings were made from observations of adenovirus (AV) infections in Seattle VW families, 1965-1969, which extended the 1961-1965 New York VW studies: That infections are predominantly enteric, may be abortive or invasive and followed by persistent intermittent excretion was confirmed. That such excretion is most characteristic of types 1, 2, 3 and 5 viruses may explain why these types were usually endemic. However, since observed duration of excretion was not increased despite a longer average observation period, persistent excretion appears not to continue indefinitely and generation-to-generation transmission now seems improbable. Unilike New York, alternate cycling of types 1 and 2 viruses was not seen. Among homotypic susceptibles, infection rates for the endemic types were highest in infants (greater than 90% for types 1 and 2), decreased with age in older children but increased in parents, perhaps because of closer contact with infants. Development of serum neutralizing antibody was most frequent (about 90%) after types 1 and 2 infection; in all cases, titers decayed over time. While delayed virus spread related to persistent intermittent excretion did occur, spread closely following new or renewed (after larger than or equal to 3 months) excretion was more important. Sibling introducers were more effective spreaders than infants, and duration of excretion was more important than mode. These data indicate that homotypic immunity is 85% protective against infection. A protective effect of heterotypic immunity could not be shown. Illness (chiefly respiratory and often febrile) was associated with 49% of infections in susceptibles and with 65% when respiratory shedding occurred. The contribution of AV to all infectious illness, based on virus-positive infections only, was 5% in infants and 3% in the 2-4-year age group; for febrile illness, the corresponding contributions were about 10% and 5%. Inclusion of infections discovered only be serology (49% of all infections) would greatly increase the contribution of AV to illness.", "contents": "The Seattle Virus Watch. VII. Observations of adenovirus infections. The following findings were made from observations of adenovirus (AV) infections in Seattle VW families, 1965-1969, which extended the 1961-1965 New York VW studies: That infections are predominantly enteric, may be abortive or invasive and followed by persistent intermittent excretion was confirmed. That such excretion is most characteristic of types 1, 2, 3 and 5 viruses may explain why these types were usually endemic. However, since observed duration of excretion was not increased despite a longer average observation period, persistent excretion appears not to continue indefinitely and generation-to-generation transmission now seems improbable. Unilike New York, alternate cycling of types 1 and 2 viruses was not seen. Among homotypic susceptibles, infection rates for the endemic types were highest in infants (greater than 90% for types 1 and 2), decreased with age in older children but increased in parents, perhaps because of closer contact with infants. Development of serum neutralizing antibody was most frequent (about 90%) after types 1 and 2 infection; in all cases, titers decayed over time. While delayed virus spread related to persistent intermittent excretion did occur, spread closely following new or renewed (after larger than or equal to 3 months) excretion was more important. Sibling introducers were more effective spreaders than infants, and duration of excretion was more important than mode. These data indicate that homotypic immunity is 85% protective against infection. A protective effect of heterotypic immunity could not be shown. Illness (chiefly respiratory and often febrile) was associated with 49% of infections in susceptibles and with 65% when respiratory shedding occurred. The contribution of AV to all infectious illness, based on virus-positive infections only, was 5% in infants and 3% in the 2-4-year age group; for febrile illness, the corresponding contributions were about 10% and 5%. Inclusion of infections discovered only be serology (49% of all infections) would greatly increase the contribution of AV to illness."}
{"id": "PMID:192074", "title": "Partial and total iodide organification defect in different sibships in a kindred.", "content": "Identical twins with goiter but without intellectual retardation and with slightly delayed bone age were found to have defective iodide organification as demonstrated by incomplete perchlorate discharge tests. They are grandnieces of a normal member of a sibship which included four children with severe retardation and complete thyroid iodide organification defect. The parents and grandparents are not consanguine. Possible explanations are considered for the problem of why the disorder is manifest completely in one sibship and only partially in the other.", "contents": "Partial and total iodide organification defect in different sibships in a kindred. Identical twins with goiter but without intellectual retardation and with slightly delayed bone age were found to have defective iodide organification as demonstrated by incomplete perchlorate discharge tests. They are grandnieces of a normal member of a sibship which included four children with severe retardation and complete thyroid iodide organification defect. The parents and grandparents are not consanguine. Possible explanations are considered for the problem of why the disorder is manifest completely in one sibship and only partially in the other."}
{"id": "PMID:192076", "title": "Chronic lymphoproliferative disorder with unusual clinical, morphologic, ultrastructural and membrane surface marker characteristics.", "content": "Four of 105 patients with chronic lymphocytic leukemia (CLL) manifested clinical, morphologic, ultrastructural and membrane surface marker characteristics that differed from those found in patients with typical CLL of demonstrated B-lymphocyte origin. These four patients presented with moderate increases in absolute lymphocyte counts, absolute neutropenia, polyclonal hypergammaglobulinemia and hepatosplenomegaly without lymphadenopathy. Two of them were unusually young, 19 and 25 years old, at the time of diagnosis. The proliferating lymphocytes carried receptors for sheep erythrocytes, a T-lymphocyte marker. In the three patients tested, the lymphocytes also carried Fc receptors. Ultrastructurally the lymphocytes contained cytoplasmic inclusion bodies consisting of parallel tubular arrays. The parallel tubular arrays corresponded to prominent cytoplasmic azurophilic granules on light microscopy. Parallel tubular arrays were found in less than 1 per cent of the lymphocytes in eight patients with typical B-lymphocyte CLL. The process in these four patients may be a distinctive chronic lymphoproliferative disorder originating in T lymphocytes with Fc receptors found in small numbers in the blood of normal persons.", "contents": "Chronic lymphoproliferative disorder with unusual clinical, morphologic, ultrastructural and membrane surface marker characteristics. Four of 105 patients with chronic lymphocytic leukemia (CLL) manifested clinical, morphologic, ultrastructural and membrane surface marker characteristics that differed from those found in patients with typical CLL of demonstrated B-lymphocyte origin. These four patients presented with moderate increases in absolute lymphocyte counts, absolute neutropenia, polyclonal hypergammaglobulinemia and hepatosplenomegaly without lymphadenopathy. Two of them were unusually young, 19 and 25 years old, at the time of diagnosis. The proliferating lymphocytes carried receptors for sheep erythrocytes, a T-lymphocyte marker. In the three patients tested, the lymphocytes also carried Fc receptors. Ultrastructurally the lymphocytes contained cytoplasmic inclusion bodies consisting of parallel tubular arrays. The parallel tubular arrays corresponded to prominent cytoplasmic azurophilic granules on light microscopy. Parallel tubular arrays were found in less than 1 per cent of the lymphocytes in eight patients with typical B-lymphocyte CLL. The process in these four patients may be a distinctive chronic lymphoproliferative disorder originating in T lymphocytes with Fc receptors found in small numbers in the blood of normal persons."}
{"id": "PMID:192077", "title": "The epidemiology of viral hepatitis: an overview.", "content": "Type A hepatitis maintains itself in human populations without either an extrahuman or human reservoir. Intestinal carriers do not appear to be epidemiologically important; viremic carriers have not been demonstrated. Person-to-person transmission by the fecal-oral route is the usual mechanism. Epidemic and endemic occurrence is usually recognizable by well-defined characteristics; a \"hyperendemic\" patern has been documented. In some countries, but not all, the long-term trend of type A disease has been downward in recent years. Type B hepatitis is worldwide in distribution, and capable of maintaining itself by the carrier reservoir. Transmission is by multiple mechanisms, with the percutaneous route still of major importance when adequately defined in terms of subtle exposures. Contact-associated transmission probably occurs by both the oral-oral and venereal routes. The long-term trend of type B hepatitis is unknown, but some evidence suggests an increase in the United States apart from the epidemic associated with drug abuse. The existence of additional viruses of human hepatitis is suggested by data concerning transfusion-associated disease and multiple episodes in the same individual.", "contents": "The epidemiology of viral hepatitis: an overview. Type A hepatitis maintains itself in human populations without either an extrahuman or human reservoir. Intestinal carriers do not appear to be epidemiologically important; viremic carriers have not been demonstrated. Person-to-person transmission by the fecal-oral route is the usual mechanism. Epidemic and endemic occurrence is usually recognizable by well-defined characteristics; a \"hyperendemic\" patern has been documented. In some countries, but not all, the long-term trend of type A disease has been downward in recent years. Type B hepatitis is worldwide in distribution, and capable of maintaining itself by the carrier reservoir. Transmission is by multiple mechanisms, with the percutaneous route still of major importance when adequately defined in terms of subtle exposures. Contact-associated transmission probably occurs by both the oral-oral and venereal routes. The long-term trend of type B hepatitis is unknown, but some evidence suggests an increase in the United States apart from the epidemic associated with drug abuse. The existence of additional viruses of human hepatitis is suggested by data concerning transfusion-associated disease and multiple episodes in the same individual."}
{"id": "PMID:192081", "title": "Cholangiocarcinomas induced by feeding 3'-methyl-4-dimethylaminoazobenzene to rats. Histopathology and ultrastructure.", "content": "Thirty-three male Sprague-Dawley rats were fed a carcinogenic (0.064% 3'-methyl-4-dimethylaminoazobenzene, 3'-Me-DAB) ground meal normal diet. After 12 weeks the ground meal diet was replaced with a normal pellet diet, and the 30 surviving animals were divided into three equal groups. One group was sacrificed at the twelfth week and the other groups 4 and 8 weeks later. Control animals were also run. Based on previous studies which used \"tumor-promoting\" diets and 3'-Me-DAB, we expected a less than 100% incidence of predominantly hepatocellular carcinomas. However, we found mucin-producing cholangiocarcinomas in all 30 animals and, in addition, a small hepatocellular component in 3 of the animals. By electron microscopy the intestinal mucosal features of microvillous border cells, goblet cells, and endocrine-like cells were found. We suggest that the tumors produced as described here provide a good animal model of mucin-producing cholangiocarcinomas.", "contents": "Cholangiocarcinomas induced by feeding 3'-methyl-4-dimethylaminoazobenzene to rats. Histopathology and ultrastructure. Thirty-three male Sprague-Dawley rats were fed a carcinogenic (0.064% 3'-methyl-4-dimethylaminoazobenzene, 3'-Me-DAB) ground meal normal diet. After 12 weeks the ground meal diet was replaced with a normal pellet diet, and the 30 surviving animals were divided into three equal groups. One group was sacrificed at the twelfth week and the other groups 4 and 8 weeks later. Control animals were also run. Based on previous studies which used \"tumor-promoting\" diets and 3'-Me-DAB, we expected a less than 100% incidence of predominantly hepatocellular carcinomas. However, we found mucin-producing cholangiocarcinomas in all 30 animals and, in addition, a small hepatocellular component in 3 of the animals. By electron microscopy the intestinal mucosal features of microvillous border cells, goblet cells, and endocrine-like cells were found. We suggest that the tumors produced as described here provide a good animal model of mucin-producing cholangiocarcinomas."}
{"id": "PMID:192082", "title": "Canine hyperlipoproteinemia and atherosclerosis. Accumulation of lipid by aortic medial cells in vivo and in vitro.", "content": "Dogs maintained for 1 year on a semisynthetic diet containing hydrogenated coconut oil and cholesterol developed hypercholesterolemia. In those cases where plasma cholesterol levels exceeded 750 mg/100 ml, the animals also developed severe atherosclerosis. This atherogenic hyperlipoproteinemia was characterized by the presence of beta very low density lipoproteins (B-VLDL), increased levels of low density lipoproteins (LDL), and the occurrence of the HDLc lipoproteins. In all of these cholesterol-rich lipoproteins the arginine-rich apoprotein (ARP) was prominent. Moreover, the HDLc (d = 1.006-1.02) contained the ARP as the only detectable apoprotein. The atherosclerosis involved the abdominal aorta, coronary and cerebrovascular arteries, and many of the peripheral arteries. Histologically, the aortic lesions were characterized by a variable intimal proliferative response and extensive medial lipid deposition. In the peripheral, coronary, and cerebral arteries, the lesions were more extensive and involved primarily the media of the vessel wall, with little intimal reaction in many cases. The correlation between the in vivo disease process and the response of aortic smooth muscle cells (SMC) grown in tissue culture to the various cholesterol-induced lipoproteins was examined. B-VLDL, LDL, and HDLc (but not HDL2) caused a marked accumulation of free and esterified cholesterol in the SMC. The cholesterol accumulation was found to be more extensive in canine SMC than in swine smooth muscle cells or smooth muscle cells of other species in response to a similar lipoprotein cholesterol concentration. The enhanced sterol uptake appeared to be a property of canine smooth muscle cells rather than a property of the canine lipoproteins. These in vitro results may be related to the observed propensity for the development of medical disease that was demonstrated in the in vivo studies.", "contents": "Canine hyperlipoproteinemia and atherosclerosis. Accumulation of lipid by aortic medial cells in vivo and in vitro. Dogs maintained for 1 year on a semisynthetic diet containing hydrogenated coconut oil and cholesterol developed hypercholesterolemia. In those cases where plasma cholesterol levels exceeded 750 mg/100 ml, the animals also developed severe atherosclerosis. This atherogenic hyperlipoproteinemia was characterized by the presence of beta very low density lipoproteins (B-VLDL), increased levels of low density lipoproteins (LDL), and the occurrence of the HDLc lipoproteins. In all of these cholesterol-rich lipoproteins the arginine-rich apoprotein (ARP) was prominent. Moreover, the HDLc (d = 1.006-1.02) contained the ARP as the only detectable apoprotein. The atherosclerosis involved the abdominal aorta, coronary and cerebrovascular arteries, and many of the peripheral arteries. Histologically, the aortic lesions were characterized by a variable intimal proliferative response and extensive medial lipid deposition. In the peripheral, coronary, and cerebral arteries, the lesions were more extensive and involved primarily the media of the vessel wall, with little intimal reaction in many cases. The correlation between the in vivo disease process and the response of aortic smooth muscle cells (SMC) grown in tissue culture to the various cholesterol-induced lipoproteins was examined. B-VLDL, LDL, and HDLc (but not HDL2) caused a marked accumulation of free and esterified cholesterol in the SMC. The cholesterol accumulation was found to be more extensive in canine SMC than in swine smooth muscle cells or smooth muscle cells of other species in response to a similar lipoprotein cholesterol concentration. The enhanced sterol uptake appeared to be a property of canine smooth muscle cells rather than a property of the canine lipoproteins. These in vitro results may be related to the observed propensity for the development of medical disease that was demonstrated in the in vivo studies."}
{"id": "PMID:192079", "title": "Gastrointestinal and metabolic function in patients with the carcinoid syndrome.", "content": "We evaluated gastrointestinal absorption in six consecutive patients with metastatic serotonin-secreting carcinoid tumors. One patient had a consistent defect in fat absorption and two other patients malabsorbed fat during spontaneous or dopamine-induced exacerbation of the carcinoid syndrome. The steatorrhea of the patient with the persistent defect in fat absorption was reduced when tumor serotonin production was reduced by the tryptophan hydroxylase inhibitor parachlorophenylalanine. The six patients had normal hemoglobin levels and the serum concentration of the following urinary constituents was normal in most of the patients: albumin, carotene, 25-hydroxycalciferol, parathyroid hormone, calcitonin, calcium, phosphorous, osteogenous alkaline phosphatase, cholesterol, triglycerides, and serum lipoproteins. The excretion of the following urinary constituents was also normal in most of the patients: creatinine clearance, tubular reabsorption of phosphorous, calcium, D-xylose, cyclic 3'5' monophosphate and hydroxyproline. We conclude that patients with the carcinoid syndrome may have steatorrhea, and that their hyperserotoninemia plays a role in this process.", "contents": "Gastrointestinal and metabolic function in patients with the carcinoid syndrome. We evaluated gastrointestinal absorption in six consecutive patients with metastatic serotonin-secreting carcinoid tumors. One patient had a consistent defect in fat absorption and two other patients malabsorbed fat during spontaneous or dopamine-induced exacerbation of the carcinoid syndrome. The steatorrhea of the patient with the persistent defect in fat absorption was reduced when tumor serotonin production was reduced by the tryptophan hydroxylase inhibitor parachlorophenylalanine. The six patients had normal hemoglobin levels and the serum concentration of the following urinary constituents was normal in most of the patients: albumin, carotene, 25-hydroxycalciferol, parathyroid hormone, calcitonin, calcium, phosphorous, osteogenous alkaline phosphatase, cholesterol, triglycerides, and serum lipoproteins. The excretion of the following urinary constituents was also normal in most of the patients: creatinine clearance, tubular reabsorption of phosphorous, calcium, D-xylose, cyclic 3'5' monophosphate and hydroxyproline. We conclude that patients with the carcinoid syndrome may have steatorrhea, and that their hyperserotoninemia plays a role in this process."}
{"id": "PMID:192083", "title": "Ultrastructural localization of membrane phosphatases in teratocarcinoma and early embryos.", "content": "Ectodermal cells of the two- and three-germ layer-thick mouse egg-cylinders are considered to be the progenitors of embryonal carcinoma cells in embryo-derived teratocarcinomas. In an attempt to find differences between the tumor cells and equivalent embryonic cells, we have studied the electron microscopic cytochemical localization of alkaline phosphatase, 5'-nucleotidase, and Mg2+-activated adenosine triphosphatase (ATPase) in embryo-derived teratocarcinomas and mouse egg-cylinders. Alkaline phosphatase was detected in both embryonic and tumor cells, but its activity appeared much more intense in the tumor cells. No ATPase was demonstrated in embryonic ectodermal cells of 6-day-old embryos and only in occasional  cells of 7- and 8-day-old embryos. No 5'-nucleotidase activity could be demonstrated in 6- to 8-day-old cylinders. There was marked ATPase and 5'-nucleotidase activity in the membranes of embryonal carcinoma cells. These data point out some differences on the plasma membrane between the embryonal carcinoma cells and equivalent embryonic cells. The potential significance of these differences is discussed with regards to the transformation of embryonic cells in tumor cells. (Am J Pathol 87:297-310, 1977).", "contents": "Ultrastructural localization of membrane phosphatases in teratocarcinoma and early embryos. Ectodermal cells of the two- and three-germ layer-thick mouse egg-cylinders are considered to be the progenitors of embryonal carcinoma cells in embryo-derived teratocarcinomas. In an attempt to find differences between the tumor cells and equivalent embryonic cells, we have studied the electron microscopic cytochemical localization of alkaline phosphatase, 5'-nucleotidase, and Mg2+-activated adenosine triphosphatase (ATPase) in embryo-derived teratocarcinomas and mouse egg-cylinders. Alkaline phosphatase was detected in both embryonic and tumor cells, but its activity appeared much more intense in the tumor cells. No ATPase was demonstrated in embryonic ectodermal cells of 6-day-old embryos and only in occasional  cells of 7- and 8-day-old embryos. No 5'-nucleotidase activity could be demonstrated in 6- to 8-day-old cylinders. There was marked ATPase and 5'-nucleotidase activity in the membranes of embryonal carcinoma cells. These data point out some differences on the plasma membrane between the embryonal carcinoma cells and equivalent embryonic cells. The potential significance of these differences is discussed with regards to the transformation of embryonic cells in tumor cells. (Am J Pathol 87:297-310, 1977)."}
{"id": "PMID:192084", "title": "Effects of hormones on 3', 5' -cyclic adenosine monophosphate in choroid plexus.", "content": "Choroid plexus of rabbit and rat was incubated for 2-30 min at 37 degrees C under 95% O2-5% CO2 in Tyrode solution containing 10 mM glucose and 1 mM theophylline with these agents: epinephrine, norepinephrine, isoproterenol, dopamine, histamine, serotonin, arginine, and lysine vasopressins, oxytocin, angiotensin, adrenocorticotropin (ACTH), beta-melanocyte-stimulating hormone, and choroid plexus peptide IIF. After incubation, tissue and medium were analyzed for 3', 5' -cyclic adenosine monophosphate (cAMP) content. Each amine or peptide was tested initially at 1,000 microng/ml. Only ACTH and serotonin affected cAMP content of rabbit choroid plexus. At 1,000 microng/ml, these agents caused a 10 and 4 times (respectively) increase in cAMP content of tissue + medium at 2-10 min with decline in content at 10-30 min. More than 90% of the increment was located in  tissue, less than 10% in medium. Minimal effective dose (MED) to cause a significant (P less than .05) accumulation of cAMP was 0.1 microng/ml (2.2 x 10(-8) M) for ACTH and 10 microng/ml (5.7 x10(-3) M) for serotonin. Only isoproterenol, epinephrine, and norepinephrine influenced cAMP content of rat choroid plexus. MED's for this effect by isoproterenol, epinephrine, and norepinephrine were .001, .01, and 10 microng/ml (4.7 x 10(-9), 5.5 x 10(-8), and 5.9 x 10(-5) M), respectively.", "contents": "Effects of hormones on 3', 5' -cyclic adenosine monophosphate in choroid plexus. Choroid plexus of rabbit and rat was incubated for 2-30 min at 37 degrees C under 95% O2-5% CO2 in Tyrode solution containing 10 mM glucose and 1 mM theophylline with these agents: epinephrine, norepinephrine, isoproterenol, dopamine, histamine, serotonin, arginine, and lysine vasopressins, oxytocin, angiotensin, adrenocorticotropin (ACTH), beta-melanocyte-stimulating hormone, and choroid plexus peptide IIF. After incubation, tissue and medium were analyzed for 3', 5' -cyclic adenosine monophosphate (cAMP) content. Each amine or peptide was tested initially at 1,000 microng/ml. Only ACTH and serotonin affected cAMP content of rabbit choroid plexus. At 1,000 microng/ml, these agents caused a 10 and 4 times (respectively) increase in cAMP content of tissue + medium at 2-10 min with decline in content at 10-30 min. More than 90% of the increment was located in  tissue, less than 10% in medium. Minimal effective dose (MED) to cause a significant (P less than .05) accumulation of cAMP was 0.1 microng/ml (2.2 x 10(-8) M) for ACTH and 10 microng/ml (5.7 x10(-3) M) for serotonin. Only isoproterenol, epinephrine, and norepinephrine influenced cAMP content of rat choroid plexus. MED's for this effect by isoproterenol, epinephrine, and norepinephrine were .001, .01, and 10 microng/ml (4.7 x 10(-9), 5.5 x 10(-8), and 5.9 x 10(-5) M), respectively."}
{"id": "PMID:192085", "title": "Oxidative response to aldosterone of pyridine nucleotide in rat kidney in situ.", "content": "In an attempt to elucidate early biochemical events in the action of aldosterone on rat kidney in situ, the response of the pyridine nucleotide oxidation-reduction state of surface cells was directly and continuously recorded with an organ-fluorometer. Intravenous administration of aldosterone induced a rapid (maximum response in 10 min) and dose-related (2.5-25 microng/100 g rat) oxidative response that was specific to aldosterone and to the kidney. The oxidative response was 1) detectable with minute dise (approximately 0.2 microng/100 g rat) of hormone: 2) reproduced by other mineralocorticoids; 3) enhanced by a maneuver for expanding the extracellular fluid compartment or by adrenalectomy; and 4) prevented by spironolactone, progesterone, actinomycin D, and cycloheximide. All of these data argue that the redox response is related to the subsequent changes in aldosteronemediated ion transport. Experiments with an uncoupler and with redox substrates showed that mitochondrial NADH was the major nucleotide pool responding to hormone. The oxidation was not accompanied by changes in the adenylate energy charge level of the whole organ. These observations support the view that aldosterone acts on energy metabolism of tubular cells before developing apparent cation transport effects.", "contents": "Oxidative response to aldosterone of pyridine nucleotide in rat kidney in situ. In an attempt to elucidate early biochemical events in the action of aldosterone on rat kidney in situ, the response of the pyridine nucleotide oxidation-reduction state of surface cells was directly and continuously recorded with an organ-fluorometer. Intravenous administration of aldosterone induced a rapid (maximum response in 10 min) and dose-related (2.5-25 microng/100 g rat) oxidative response that was specific to aldosterone and to the kidney. The oxidative response was 1) detectable with minute dise (approximately 0.2 microng/100 g rat) of hormone: 2) reproduced by other mineralocorticoids; 3) enhanced by a maneuver for expanding the extracellular fluid compartment or by adrenalectomy; and 4) prevented by spironolactone, progesterone, actinomycin D, and cycloheximide. All of these data argue that the redox response is related to the subsequent changes in aldosteronemediated ion transport. Experiments with an uncoupler and with redox substrates showed that mitochondrial NADH was the major nucleotide pool responding to hormone. The oxidation was not accompanied by changes in the adenylate energy charge level of the whole organ. These observations support the view that aldosterone acts on energy metabolism of tubular cells before developing apparent cation transport effects."}
{"id": "PMID:192086", "title": "Effects of insulin, ADH, and cyclic AMP on sodium transport in the toad bladder.", "content": "These studies further define the mechanisms by which insulin stimulates Na transport in the toad bladder. Serosal but not mucosal addition of insulin, 100-1,000 mU/ml, stimulated short-circuit current (SCC) by 25-50%. The initial rise in SCC occurred at 5 min and the peak response at 15-25 min. Doses of insulin greater than 250 mU/ml increased SCC values for up to 3 h. Actinomycin D did not block the early rise in SCC produced by insulin, but it blocked the delayed effects. Insulin increased SCC in substrate-depleted bladders, although the increase in SCC was less (P less than 0.01) than in nonsubstrate-depleted bladders. Pyruvate addition to substrate-depleted bladders restored to normal the rise in SCC observed after insulin. Simultaneous addition of ADH and insulin led to an increase in SCC that was greater than the sum of the responses observed when each hormone was added independently. Synergistic effects on SCC were also obtained with cyclic AMP and insulin. Insulin did not increase cyclic AMP levels in toad bladder epithelial cells. It is suggested that insulin stimulates active Na transport by two mechanisms: 1) a rapid phase, which may involve unmasking of pump sites within the membrane, and 2) a delayed effect which seems to require protein synthesis. The synergism of which seems to require protein synthesis. The synergism of insulin with ADH or cyclic AMP may reflect a facilitative effect of insulin on ADH or cyclic AMP-sensitive pump sites or, alternatively, the uncovering of latent pump sites that then may be available to stimulation by ADH or cyclic AMP.", "contents": "Effects of insulin, ADH, and cyclic AMP on sodium transport in the toad bladder. These studies further define the mechanisms by which insulin stimulates Na transport in the toad bladder. Serosal but not mucosal addition of insulin, 100-1,000 mU/ml, stimulated short-circuit current (SCC) by 25-50%. The initial rise in SCC occurred at 5 min and the peak response at 15-25 min. Doses of insulin greater than 250 mU/ml increased SCC values for up to 3 h. Actinomycin D did not block the early rise in SCC produced by insulin, but it blocked the delayed effects. Insulin increased SCC in substrate-depleted bladders, although the increase in SCC was less (P less than 0.01) than in nonsubstrate-depleted bladders. Pyruvate addition to substrate-depleted bladders restored to normal the rise in SCC observed after insulin. Simultaneous addition of ADH and insulin led to an increase in SCC that was greater than the sum of the responses observed when each hormone was added independently. Synergistic effects on SCC were also obtained with cyclic AMP and insulin. Insulin did not increase cyclic AMP levels in toad bladder epithelial cells. It is suggested that insulin stimulates active Na transport by two mechanisms: 1) a rapid phase, which may involve unmasking of pump sites within the membrane, and 2) a delayed effect which seems to require protein synthesis. The synergism of which seems to require protein synthesis. The synergism of insulin with ADH or cyclic AMP may reflect a facilitative effect of insulin on ADH or cyclic AMP-sensitive pump sites or, alternatively, the uncovering of latent pump sites that then may be available to stimulation by ADH or cyclic AMP."}
{"id": "PMID:192087", "title": "Effect of sodium fluoride on concentrating and diluting ability in the rat.", "content": "Mechanisms for the concentrating defect produced by fluoride were examined in the rat. Free-water clearance at all levels of delivery was normal after 5 days of chronic fluoride administration in the hereditary hypothalamic diabetes insipidus rat. In the Sprague-Dawley rats, during moderate fluoride administration (120 micronmol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased, but after exogenous vasopressin, volume decreased and osmolality and cyclic AMP increased appropriately. During larger daily doses of fluoride (240 micronmol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin. These data suggest that ascending limb chloride reabsorption is unaltered by fluoride administration; in the presence of sufficient fluoride, collecting tubular cells apparently do not generate cyclic AMP or increase permeability appropriately in response to vasopressin. The postulated defect is felt to be due to either a decrease in ATP availability or to a direct inhibitory effect of fluoride on the vasopressin-dependent cyclic AMP generating system.", "contents": "Effect of sodium fluoride on concentrating and diluting ability in the rat. Mechanisms for the concentrating defect produced by fluoride were examined in the rat. Free-water clearance at all levels of delivery was normal after 5 days of chronic fluoride administration in the hereditary hypothalamic diabetes insipidus rat. In the Sprague-Dawley rats, during moderate fluoride administration (120 micronmol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased, but after exogenous vasopressin, volume decreased and osmolality and cyclic AMP increased appropriately. During larger daily doses of fluoride (240 micronmol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin. These data suggest that ascending limb chloride reabsorption is unaltered by fluoride administration; in the presence of sufficient fluoride, collecting tubular cells apparently do not generate cyclic AMP or increase permeability appropriately in response to vasopressin. The postulated defect is felt to be due to either a decrease in ATP availability or to a direct inhibitory effect of fluoride on the vasopressin-dependent cyclic AMP generating system."}
{"id": "PMID:192088", "title": "Cyclic AMP in action of antidiuretic hormone: effects of exogenous cyclic AMP and its new analogue.", "content": "Exogenous cyclic 3',5'-adenosine monophosphate (cAMP) stimulates the effect of the antidiuretic hormone, vasopressin (VP), only in pharmacologic quantities and results have often been inconsistent. The present study examined the ability of a new analogue, 8-[p-Cl-phenylthio]cyclic 3',5'-adenosine monophosphate (C1-PheS-cAMP) to mimic the effect of VP, both biochemically (protein kinase activation) and functionally (hydrosomatic response of perfused collecting tubules) in mammalian kidney tissue. C1PheS-cAMP was found to be about 100 times as effective as cAMP both biochemically and functionally. The increased effectiveness of C1PheS-cAMP is probably is probably due to a greater permeability across the cell membrane and to the resistance of C1PheS-cAMP to enzymatic degradation, Cyclic AMP phosphodiesterase inhibition was observed with C1PheS-cAMP, but its contribution to overall effect was minor. C1PheS-cAMP was found to be more effective than exogenous vasopressin, an effect probably due primarily to its resistance to catabolism. The results provide further new evidence that cAMP and protein kinase are involved in the cellular action of vasopressin. C1PheS-cAMP proved to be a useful tool in the study of hormone action, especially in steps subsequent to cAMP generation.", "contents": "Cyclic AMP in action of antidiuretic hormone: effects of exogenous cyclic AMP and its new analogue. Exogenous cyclic 3',5'-adenosine monophosphate (cAMP) stimulates the effect of the antidiuretic hormone, vasopressin (VP), only in pharmacologic quantities and results have often been inconsistent. The present study examined the ability of a new analogue, 8-[p-Cl-phenylthio]cyclic 3',5'-adenosine monophosphate (C1-PheS-cAMP) to mimic the effect of VP, both biochemically (protein kinase activation) and functionally (hydrosomatic response of perfused collecting tubules) in mammalian kidney tissue. C1PheS-cAMP was found to be about 100 times as effective as cAMP both biochemically and functionally. The increased effectiveness of C1PheS-cAMP is probably is probably due to a greater permeability across the cell membrane and to the resistance of C1PheS-cAMP to enzymatic degradation, Cyclic AMP phosphodiesterase inhibition was observed with C1PheS-cAMP, but its contribution to overall effect was minor. C1PheS-cAMP was found to be more effective than exogenous vasopressin, an effect probably due primarily to its resistance to catabolism. The results provide further new evidence that cAMP and protein kinase are involved in the cellular action of vasopressin. C1PheS-cAMP proved to be a useful tool in the study of hormone action, especially in steps subsequent to cAMP generation."}
{"id": "PMID:192089", "title": "Computer simulation of ischemic rat heart purine metabolism. I. Model construction.", "content": "A model is proposed for the partial depletion of the adenine nucleotide pool in the ischemic perfused rat heart which involves seven enzymes: adenylate cyclase, 3',5'-cyclic AMP phosphodiesterase, 5'-nucleotidase, adenosine kinase, adenosine deaminase, purine nucleoside phosphorylase, and inorganic pyrophosphatase. The computer implementation of this model is in terms of rate laws, several of which were obtained by a systematic least-squares fitting procedure. Depletion of the adenine nucleotide pool is initiated by the release of endogenous noradrenaline into the interstitial fluid, which results from a fall in tissue PO2, and the subsequent activation of adenylate cyclase. In this model the substrate for 5'-nucleotidase is a membrane-bound AMP pool formed by hydrolysis of extracellular fluid and functions as a vasodilator; excess adenosine is incorporated into the tissue by a \"permease\" with Michaelis-Menten kinetics and converted to AMP, inosine, and hypoxanthine. Alternative mechanisms, such as the deamination of AMP by adenylate deaminase and conversion of AMP to adenine by AMP pyrophosphorylase, were rejected primarily on qualitative biochemical grounds.", "contents": "Computer simulation of ischemic rat heart purine metabolism. I. Model construction. A model is proposed for the partial depletion of the adenine nucleotide pool in the ischemic perfused rat heart which involves seven enzymes: adenylate cyclase, 3',5'-cyclic AMP phosphodiesterase, 5'-nucleotidase, adenosine kinase, adenosine deaminase, purine nucleoside phosphorylase, and inorganic pyrophosphatase. The computer implementation of this model is in terms of rate laws, several of which were obtained by a systematic least-squares fitting procedure. Depletion of the adenine nucleotide pool is initiated by the release of endogenous noradrenaline into the interstitial fluid, which results from a fall in tissue PO2, and the subsequent activation of adenylate cyclase. In this model the substrate for 5'-nucleotidase is a membrane-bound AMP pool formed by hydrolysis of extracellular fluid and functions as a vasodilator; excess adenosine is incorporated into the tissue by a \"permease\" with Michaelis-Menten kinetics and converted to AMP, inosine, and hypoxanthine. Alternative mechanisms, such as the deamination of AMP by adenylate deaminase and conversion of AMP to adenine by AMP pyrophosphorylase, were rejected primarily on qualitative biochemical grounds."}
{"id": "PMID:192091", "title": "Human poxvirus disease after smallpox eradication.", "content": "A 5-year-old boy living in a small camp in the rural Ivory Coast had a disease resembling smallpox. This occurred 4 years after smallpox had been eradicated from the Ivory Coast and 1.5 years after the last case of smallpox was detected in West and Central Africa. Clinical, serological, and epidemiological evidence indicated this disease was probably monkeypox, a poxvirus of the variola/vaccina subgroup. A serologic survey of poxvirus antibodies in the wild animal population detected neutralizing antibodies in rodents, larger mammals, primates, and birds. The laboratory and ecological characteristics of poxviruses require further elucidation, especially those which have been found in animals near human monkeypox cases.", "contents": "Human poxvirus disease after smallpox eradication. A 5-year-old boy living in a small camp in the rural Ivory Coast had a disease resembling smallpox. This occurred 4 years after smallpox had been eradicated from the Ivory Coast and 1.5 years after the last case of smallpox was detected in West and Central Africa. Clinical, serological, and epidemiological evidence indicated this disease was probably monkeypox, a poxvirus of the variola/vaccina subgroup. A serologic survey of poxvirus antibodies in the wild animal population detected neutralizing antibodies in rodents, larger mammals, primates, and birds. The laboratory and ecological characteristics of poxviruses require further elucidation, especially those which have been found in animals near human monkeypox cases."}
{"id": "PMID:192092", "title": "Studies on the epidemiology of sandfly fever in Iran. I. Virus isolates obtained from Phlebotomus.", "content": "A total of 62 virus isolates was obtained from 12,485 male and female sandflies (predominately Phlebotomus papatasi) collected in a village in central Iran during the summer of 1975. The overall virus isolation rate from female sandflies was 1 per 177 insects processed. Of the 62 virus strains obtained, 49 were identified as Sicilian virus, 11 as Karimabad, and 2 as a new member of the vesicular stomatitis serogroup. One isolate each of Sicilian and Karimabad virus was made from pools of male sandflies. The  three virus types were active in the sandfly population simultaneously. Sicilian virus isolation rates showed little variation during the study period, suggesting continuous virus activity during the sandfly season. The implications of these findings for the epidemiology of sandfly fever are discussed.", "contents": "Studies on the epidemiology of sandfly fever in Iran. I. Virus isolates obtained from Phlebotomus. A total of 62 virus isolates was obtained from 12,485 male and female sandflies (predominately Phlebotomus papatasi) collected in a village in central Iran during the summer of 1975. The overall virus isolation rate from female sandflies was 1 per 177 insects processed. Of the 62 virus strains obtained, 49 were identified as Sicilian virus, 11 as Karimabad, and 2 as a new member of the vesicular stomatitis serogroup. One isolate each of Sicilian and Karimabad virus was made from pools of male sandflies. The  three virus types were active in the sandfly population simultaneously. Sicilian virus isolation rates showed little variation during the study period, suggesting continuous virus activity during the sandfly season. The implications of these findings for the epidemiology of sandfly fever are discussed."}
{"id": "PMID:192093", "title": "Studies on the epidemiology of sandfly fever in Iran. II. The prevalence of human and animal infection with five phlebotomus fever virus serotypes in Isfahan province.", "content": "Human and animal sera from an endemic area of sandfly fever in Iran were tested by plaque reduction neutralization method against five different Phlebotomus fever virus serotypes (Naples, Sicilian, Karimabad, Salehabad, and I-47). The overall prevalence of Naples, Sicilian, and Karimabad virus antibodies among the human population was 17%, 25%, and 66%, respectively. All sera were negative against Salehabad and I-47 viruses. Age-specific antibody rates suggested that Sicilian and Karimabad viruses were endemic in the study area but that Naples virus activity was sporadic. These observations were confirmed by isolations of Sicilian and Karimabad viruses from sandflies collected in the study area. Among the animal sera tested, evidence of Phlebotomus fever virus infection was detected only in gerbils. Of 38 Rhombomys opimus tested, 34% had neutralizing antibodies against Sicilian virus and 32% against Karimabad. These results indicate that gerbils are infected with these two viruses and possibly might serve as reservoirs or amplifying hosts. The serologic studies also suggest that the ecology of Sicilian and Karimabad viruses involves chiefly sandflies, gerbils, and man, an epidemiologic pattern previously demonstrated for cutaneous leishmaniasis in the same region of Iran.", "contents": "Studies on the epidemiology of sandfly fever in Iran. II. The prevalence of human and animal infection with five phlebotomus fever virus serotypes in Isfahan province. Human and animal sera from an endemic area of sandfly fever in Iran were tested by plaque reduction neutralization method against five different Phlebotomus fever virus serotypes (Naples, Sicilian, Karimabad, Salehabad, and I-47). The overall prevalence of Naples, Sicilian, and Karimabad virus antibodies among the human population was 17%, 25%, and 66%, respectively. All sera were negative against Salehabad and I-47 viruses. Age-specific antibody rates suggested that Sicilian and Karimabad viruses were endemic in the study area but that Naples virus activity was sporadic. These observations were confirmed by isolations of Sicilian and Karimabad viruses from sandflies collected in the study area. Among the animal sera tested, evidence of Phlebotomus fever virus infection was detected only in gerbils. Of 38 Rhombomys opimus tested, 34% had neutralizing antibodies against Sicilian virus and 32% against Karimabad. These results indicate that gerbils are infected with these two viruses and possibly might serve as reservoirs or amplifying hosts. The serologic studies also suggest that the ecology of Sicilian and Karimabad viruses involves chiefly sandflies, gerbils, and man, an epidemiologic pattern previously demonstrated for cutaneous leishmaniasis in the same region of Iran."}
{"id": "PMID:192094", "title": "Isfahan virus, a new vesiculovirus infecting humans, gerbils, and sandflies in Iran.", "content": "The characteristics and ecology of Isfahan virus, a new vesicular stomatitis virus (VSV) serotype, are described. Two strains of the agent were isolated from pools of Phlebotomus papatasi collected in Iran in 1975. Its animal pathogenicity, growth rate, cytopathic effect, and plaque morphology are similar to those of the other VSV serotypes. Electron microscopic examination of the virus demonstrated a bullet shape, the presence of truncated particles and maturation at plasma membranes. Antigenic relationships between Isfahan virus and three other VSV serotypes (Cocal, Piry, and Chandipura) were demonstrated by complement fixation or neutralization tests. A high prevalence of Isfahan neutralizing antibodies was found in human sera from several regions of Iran, suggesting that the virus may be of some public health importance. All of the residents over 5 years of age in the village where the virus was isolated had been infected. Neutralizing antibodies to Isfahan virus were also found in sera of Iranian gerbils but not in domestic animals. Results of this study suggest that the ecology of Isfahan virus is distinct from the other VSV serotypes and involves chiefly humans, gerbils, and sandflies, a pattern also observed with cutaneous leishmaniasis and sandfly fever in Iran.", "contents": "Isfahan virus, a new vesiculovirus infecting humans, gerbils, and sandflies in Iran. The characteristics and ecology of Isfahan virus, a new vesicular stomatitis virus (VSV) serotype, are described. Two strains of the agent were isolated from pools of Phlebotomus papatasi collected in Iran in 1975. Its animal pathogenicity, growth rate, cytopathic effect, and plaque morphology are similar to those of the other VSV serotypes. Electron microscopic examination of the virus demonstrated a bullet shape, the presence of truncated particles and maturation at plasma membranes. Antigenic relationships between Isfahan virus and three other VSV serotypes (Cocal, Piry, and Chandipura) were demonstrated by complement fixation or neutralization tests. A high prevalence of Isfahan neutralizing antibodies was found in human sera from several regions of Iran, suggesting that the virus may be of some public health importance. All of the residents over 5 years of age in the village where the virus was isolated had been infected. Neutralizing antibodies to Isfahan virus were also found in sera of Iranian gerbils but not in domestic animals. Results of this study suggest that the ecology of Isfahan virus is distinct from the other VSV serotypes and involves chiefly humans, gerbils, and sandflies, a pattern also observed with cutaneous leishmaniasis and sandfly fever in Iran."}
{"id": "PMID:192095", "title": "Overwintering mechanism for bluetongue virus: biological recovery of latent virus from a bovine by bites of Culicoides variipennis.", "content": "Bluetongue virus (BTV) was biologically transmitted by the bites of colonized Culicoides variipennis gnats to recipient sheep from a Hereford bull with latent infection. Four biological recoveries of BTV were mediated over 2 years by multiple feedings of the vector during a 4- to 72-hour interval. Initial stimulation by gnat bites at 0 hour permitted biological recovery of BTV by gnats that fed at later intervals. The 4th biological recovery of the virus from the bull clearly indicated a vector-mediated viral recovery mechanism in which initial vector bites at 0 hours stimulated a \"showering\" of BTV into the blood stream of the bull. The BTV carrier bull developed no overt signs of illness during these studies. The pertinent BTV assay and serologic results for the 4 1/3 years of the bull's life are summarized in this report.", "contents": "Overwintering mechanism for bluetongue virus: biological recovery of latent virus from a bovine by bites of Culicoides variipennis. Bluetongue virus (BTV) was biologically transmitted by the bites of colonized Culicoides variipennis gnats to recipient sheep from a Hereford bull with latent infection. Four biological recoveries of BTV were mediated over 2 years by multiple feedings of the vector during a 4- to 72-hour interval. Initial stimulation by gnat bites at 0 hour permitted biological recovery of BTV by gnats that fed at later intervals. The 4th biological recovery of the virus from the bull clearly indicated a vector-mediated viral recovery mechanism in which initial vector bites at 0 hours stimulated a \"showering\" of BTV into the blood stream of the bull. The BTV carrier bull developed no overt signs of illness during these studies. The pertinent BTV assay and serologic results for the 4 1/3 years of the bull's life are summarized in this report."}
{"id": "PMID:192096", "title": "Hazards and safeguards during carotid endarterectomy. Technical considerations.", "content": "The hazards and safeguards of carotid endarterectomy are presented in a consecutive series of 130 patients over a fourteen month period. The mortality rate of 1.5 per cent was due to myocardial infarction. Two patients (1.5 per cent) suffered minor but permanent neurologic deficit. There was an incidence of 4.6 per cent transient neurologic deficits, all of which cleared within 24 hours. Special emphasis is placed on peripheral nerve injuries (12.3 per cent). Local neurologic anatomy is reviewed to facilitate safe dissection and an avoidance of nerve injury.", "contents": "Hazards and safeguards during carotid endarterectomy. Technical considerations. The hazards and safeguards of carotid endarterectomy are presented in a consecutive series of 130 patients over a fourteen month period. The mortality rate of 1.5 per cent was due to myocardial infarction. Two patients (1.5 per cent) suffered minor but permanent neurologic deficit. There was an incidence of 4.6 per cent transient neurologic deficits, all of which cleared within 24 hours. Special emphasis is placed on peripheral nerve injuries (12.3 per cent). Local neurologic anatomy is reviewed to facilitate safe dissection and an avoidance of nerve injury."}
{"id": "PMID:192097", "title": "Nonautonomy of parathyroid hormone and urinary cyclic AMP in primary hyperparathyroidism.", "content": "This study demonstrates that appreciable changes in serum parathyroid hormone and urinary cyclic AMP occur during experimentally induced hyper- and hypocalcemia in almost all patients with primary hyperparathyroidism regardless of histology. A single patient with tertiary hyperparathyroidism also demonstrated a significant elevation of serum parathyroid hormone and urinary cyclic AMP in response to EDTA induced reduction in ionized calcium. Thus, total autonomy of hormone secretion was not present in the great majority of the patients with a parathyroid adenoma, parathyroid hyperplasia, or the single patient with tertiary hyperparathyroidism. Therefore, preoperative evaluation of the rsponse of urinary cyclic AMP and serum parapthyroid hormone to EDTA or calcium infusion will not distinguish parathyroid adenomas from hyperplasia on the basis of total autonomy of hormone secretion. If a difference in secretory control is present between parathyroid adenomas and parathyroid hyperplasia, it is more subtle than total autonomy for adenomas and nonautonomy for hyperplasia.", "contents": "Nonautonomy of parathyroid hormone and urinary cyclic AMP in primary hyperparathyroidism. This study demonstrates that appreciable changes in serum parathyroid hormone and urinary cyclic AMP occur during experimentally induced hyper- and hypocalcemia in almost all patients with primary hyperparathyroidism regardless of histology. A single patient with tertiary hyperparathyroidism also demonstrated a significant elevation of serum parathyroid hormone and urinary cyclic AMP in response to EDTA induced reduction in ionized calcium. Thus, total autonomy of hormone secretion was not present in the great majority of the patients with a parathyroid adenoma, parathyroid hyperplasia, or the single patient with tertiary hyperparathyroidism. Therefore, preoperative evaluation of the rsponse of urinary cyclic AMP and serum parapthyroid hormone to EDTA or calcium infusion will not distinguish parathyroid adenomas from hyperplasia on the basis of total autonomy of hormone secretion. If a difference in secretory control is present between parathyroid adenomas and parathyroid hyperplasia, it is more subtle than total autonomy for adenomas and nonautonomy for hyperplasia."}
{"id": "PMID:192098", "title": "Primary benign solid tumors of the liver.", "content": "The benign solid primary tumors of the liver separate into three major groups: (1) the most common lesions--small, nodular tumors, often found incidentally with histologic features suggesting a reactive etiology, that never rupture or metastasize, that seem to grow most rapidly in children and pregnant women, and that are probably unrelated to birth control medication; (2) the less common adenomas that are purely epithelial, that most often occur in menstruating females, that often show necrosis and rupture, and that are closely associated with oral contraceptive agents; and (3) very rare tumors, usually mesenchymal, occurring solely in children. The therapeutic and prognostic implications of these tumors are defined based upon a study of 111 patients, all but one of whom have undergone resection.", "contents": "Primary benign solid tumors of the liver. The benign solid primary tumors of the liver separate into three major groups: (1) the most common lesions--small, nodular tumors, often found incidentally with histologic features suggesting a reactive etiology, that never rupture or metastasize, that seem to grow most rapidly in children and pregnant women, and that are probably unrelated to birth control medication; (2) the less common adenomas that are purely epithelial, that most often occur in menstruating females, that often show necrosis and rupture, and that are closely associated with oral contraceptive agents; and (3) very rare tumors, usually mesenchymal, occurring solely in children. The therapeutic and prognostic implications of these tumors are defined based upon a study of 111 patients, all but one of whom have undergone resection."}
{"id": "PMID:192099", "title": "Anaesthetic management of insulinoma.", "content": "The anaesthetic management of two cases of insulinoma treated by distal pancreatectomy is presented. Stress is laid on pre-operative and intra-operative glucose administration in sufficiently high quantity. Pre-operative corticosteroid therapy is better avoided. Dextrose infusion should be stopped soon after removal of the tumour to prevent excessive hyperglycemic response in the postoperative period. Methyoxyflurane was used because it tends to raise the blood sugar level. Pancuronium bromide was preferred because of the stable cardiovascular conditions it produces.", "contents": "Anaesthetic management of insulinoma. The anaesthetic management of two cases of insulinoma treated by distal pancreatectomy is presented. Stress is laid on pre-operative and intra-operative glucose administration in sufficiently high quantity. Pre-operative corticosteroid therapy is better avoided. Dextrose infusion should be stopped soon after removal of the tumour to prevent excessive hyperglycemic response in the postoperative period. Methyoxyflurane was used because it tends to raise the blood sugar level. Pancuronium bromide was preferred because of the stable cardiovascular conditions it produces."}
{"id": "PMID:192106", "title": "Effects of halothane, thiopental, and lidocaine on fluidity of synaptic plasma membranes and artificial phospholipid membranes.", "content": "The effects of halothane, thiopental, and lidocaine were studied with spin-labeling methods in synaptic plasma membranes (order parameter) and artificial phospholipid membranes (lateral diffusion). Halothane had a biphasic action, low concentrations (0.64 mM) ordering and high concentrations (2.9 mM) fluidizing both types of membranes. A biphasic effect in phospholipid membranes was also seen with thiopental, 0.1 mM ordering and 10 mM fluidizing, whereas in synaptic plasma membranes both low and high concentrations caused an increased order in the lipid bilayer region. At high thiopental concentrations, a considerable number of molecules may have reacted with membrane proteins or accumulated in the highly fluidic hydrophobic interior region of the membrane without affecting the rotational movement of the labeled fatty acid. Lidocaine alone, or together with calcium chloride, at various concentrations to 10 mM had no significant effect, and a fluidizing effect of 1 mM calcium chloride was possibly a result of interaction of calcium chloride with the label. The results indicate that the three lipid-soluble anesthetics interact differently with the lipid part of membranes. Lidocaine did not seem to affect bilyer lipids, while thiopental and halothane in phospholipid vesicles and halothane alone in synaptic membranes caused a dose-dependent biphasic effect.", "contents": "Effects of halothane, thiopental, and lidocaine on fluidity of synaptic plasma membranes and artificial phospholipid membranes. The effects of halothane, thiopental, and lidocaine were studied with spin-labeling methods in synaptic plasma membranes (order parameter) and artificial phospholipid membranes (lateral diffusion). Halothane had a biphasic action, low concentrations (0.64 mM) ordering and high concentrations (2.9 mM) fluidizing both types of membranes. A biphasic effect in phospholipid membranes was also seen with thiopental, 0.1 mM ordering and 10 mM fluidizing, whereas in synaptic plasma membranes both low and high concentrations caused an increased order in the lipid bilayer region. At high thiopental concentrations, a considerable number of molecules may have reacted with membrane proteins or accumulated in the highly fluidic hydrophobic interior region of the membrane without affecting the rotational movement of the labeled fatty acid. Lidocaine alone, or together with calcium chloride, at various concentrations to 10 mM had no significant effect, and a fluidizing effect of 1 mM calcium chloride was possibly a result of interaction of calcium chloride with the label. The results indicate that the three lipid-soluble anesthetics interact differently with the lipid part of membranes. Lidocaine did not seem to affect bilyer lipids, while thiopental and halothane in phospholipid vesicles and halothane alone in synaptic membranes caused a dose-dependent biphasic effect."}
{"id": "PMID:192108", "title": "Quantitative transmissible gastroenteritis virus shedding patterns in lactating sows.", "content": "To test the role of sows in spreading transmissible gastroenteritis (TGE), 11 sows were intravenously, intranasally, or intramammarily inoculated with virulent virus within 5 days of farrowing. Six of the sows were separated from their offspring, and 5 were allowed to nurse their litters. All sows became clinically ill with sign of anorexia, depression, and fever that persisted until postinoculation day 4 or 5. They shed virus through milk, nasal secretions, and feces, with individual variations occurring in degree and duration of shedding in the 1st week after inoculation. Of 40 pigs separately fed milk samples from the 6 inoculated sows, 19 pigs (47.5%) became sick in 24 to 40 hours, and virus was isolated from them at necropsy. Of 43 pigs in the 5 litters that nursed exposed dams, all became sick with typical signs of TGE, and 29 (67.4%) died in 2 to 9 days. Sows given the single intramammary inoculation of virus developed statistically significant higher levels of TGE virus-neutralizing antibodies than did sows inoculated intravenously or intranasally.", "contents": "Quantitative transmissible gastroenteritis virus shedding patterns in lactating sows. To test the role of sows in spreading transmissible gastroenteritis (TGE), 11 sows were intravenously, intranasally, or intramammarily inoculated with virulent virus within 5 days of farrowing. Six of the sows were separated from their offspring, and 5 were allowed to nurse their litters. All sows became clinically ill with sign of anorexia, depression, and fever that persisted until postinoculation day 4 or 5. They shed virus through milk, nasal secretions, and feces, with individual variations occurring in degree and duration of shedding in the 1st week after inoculation. Of 40 pigs separately fed milk samples from the 6 inoculated sows, 19 pigs (47.5%) became sick in 24 to 40 hours, and virus was isolated from them at necropsy. Of 43 pigs in the 5 litters that nursed exposed dams, all became sick with typical signs of TGE, and 29 (67.4%) died in 2 to 9 days. Sows given the single intramammary inoculation of virus developed statistically significant higher levels of TGE virus-neutralizing antibodies than did sows inoculated intravenously or intranasally."}
{"id": "PMID:192109", "title": "Serotyping avian adenoviruses by a microneutralization procedure.", "content": "A microneutralization procedure, using chicken kidney cell monolayers as an indicator system, was developed and applied to the serotyping of isolates characterized as avian adenoviruses. The method was determined to be reproducible, since coefficients of variation were low for 12 replicate titrations of homologous reagents of 9 prototype avian adenoviruses. Prototype reagents were specific according to results of reciprocal end point-neutralization tests and comparison of antigenic relatedness, using results obtained by previous researchers. Forty-two avian adenovirus isolates were classified into 6 serotypes by one-side end point-neutralization tests against antiserums made to 9 prototype avian adenoviruses. An additional 20 isolates were antigenically related to prototype viruses, but they could not be specifically types with the typing criteria. Different serotypes were isolated from birds having similar clinical diagnostic signs and lesions of disease.", "contents": "Serotyping avian adenoviruses by a microneutralization procedure. A microneutralization procedure, using chicken kidney cell monolayers as an indicator system, was developed and applied to the serotyping of isolates characterized as avian adenoviruses. The method was determined to be reproducible, since coefficients of variation were low for 12 replicate titrations of homologous reagents of 9 prototype avian adenoviruses. Prototype reagents were specific according to results of reciprocal end point-neutralization tests and comparison of antigenic relatedness, using results obtained by previous researchers. Forty-two avian adenovirus isolates were classified into 6 serotypes by one-side end point-neutralization tests against antiserums made to 9 prototype avian adenoviruses. An additional 20 isolates were antigenically related to prototype viruses, but they could not be specifically types with the typing criteria. Different serotypes were isolated from birds having similar clinical diagnostic signs and lesions of disease."}
{"id": "PMID:192110", "title": "Isolation and characterization of epizootic hemorrhagic disease virus from white-tailed deer (Odocoileus virginianus) in eastern Washington.", "content": "A virus was isolated from the spleen of a white-tailed deer (Odocoileus virginianus) that had died during an epizootic in Washington state in 1967. Inoculation of a 10% spleen suspension from the deer caused hemorrhagic disease in normal white-tailed deer. Studies were conducted on the biological, physicochemical, and serologic properties of the Washington isolate. An in vitro assay system, utilizing a cultured primary of white-tailed deer fetal cells from an entire fetus, was employed for isolation and propagation of the virus. Cytopathic effect was characterized by focal development of rounded and clumped cells. Propagation was unsuccessful in suckling mice, BHK-21, and Vero cell cultures. The virus was resistant to treatment with ether, sodium deoxycholate, trypsin, oxytetracycline hydrochloride, and was sensitive to chloroform. Virus yield was not affected when infected cultures were treated with 5-iodo-2'-deoxyuridine, but dactinomycin (actinomycin D) treatment of infected cultures reduced virus yield. The virus was inactivated when heated at 70 C for 5 minutes or when exposed to pH 5 for 18 hours at 4 C. The virus was completely excluded from the filtrate by a 0.10- micronm (APD) membrane filter. Staining of infected cells with acridine orange indicated the presence of double-standard nucleic acid in the cytoplasm. Serum-neutralization tests with antiserums against the homologous virus and the New Jersey and Alberta strains of epizootic hemorrhagic disease virus resulted in neutralization of the Washington isolate. The Washington virus was not neutralized by bluetongue virus antiserum. Cells infected with the Washington isolate exhibited intracytoplasmic fluorescence by the indirect fluorescent antibody method with New Jersey and Alberta epizootic hemorrhagic disease antiserums but not with bluetongue antiserum.", "contents": "Isolation and characterization of epizootic hemorrhagic disease virus from white-tailed deer (Odocoileus virginianus) in eastern Washington. A virus was isolated from the spleen of a white-tailed deer (Odocoileus virginianus) that had died during an epizootic in Washington state in 1967. Inoculation of a 10% spleen suspension from the deer caused hemorrhagic disease in normal white-tailed deer. Studies were conducted on the biological, physicochemical, and serologic properties of the Washington isolate. An in vitro assay system, utilizing a cultured primary of white-tailed deer fetal cells from an entire fetus, was employed for isolation and propagation of the virus. Cytopathic effect was characterized by focal development of rounded and clumped cells. Propagation was unsuccessful in suckling mice, BHK-21, and Vero cell cultures. The virus was resistant to treatment with ether, sodium deoxycholate, trypsin, oxytetracycline hydrochloride, and was sensitive to chloroform. Virus yield was not affected when infected cultures were treated with 5-iodo-2'-deoxyuridine, but dactinomycin (actinomycin D) treatment of infected cultures reduced virus yield. The virus was inactivated when heated at 70 C for 5 minutes or when exposed to pH 5 for 18 hours at 4 C. The virus was completely excluded from the filtrate by a 0.10- micronm (APD) membrane filter. Staining of infected cells with acridine orange indicated the presence of double-standard nucleic acid in the cytoplasm. Serum-neutralization tests with antiserums against the homologous virus and the New Jersey and Alberta strains of epizootic hemorrhagic disease virus resulted in neutralization of the Washington isolate. The Washington virus was not neutralized by bluetongue virus antiserum. Cells infected with the Washington isolate exhibited intracytoplasmic fluorescence by the indirect fluorescent antibody method with New Jersey and Alberta epizootic hemorrhagic disease antiserums but not with bluetongue antiserum."}
{"id": "PMID:192111", "title": "Equine antibody to bovine serum induced by several equine vaccines as a source of extraneous precipitin lines in the agar gel immunodiffusion test for equine infectious anemia.", "content": "Precipitin lines not associated with equine infectious anemia (EIA) were observed in routine agar gel immunodiffusion (AGID) testing for the infection. The serums which produced these lines were obtained from horses which had been given multiple vaccinations with commercially available cell culture-origin equine virus vaccines as part of a comprehensive herd health program. The lines formed against cell culture-derived, but not spleen-derived EIA viral antigens. Investigation revealed that bovine serum proteins in the vaccines induced precipitating antibodies which reacted with bovine serum proteins in cell culture-derived antigens. A vaccination trial, utilizing 4 commercially available vaccines in various combinations, indicated that as few as 2 vaccinations could induce AGID-detectable antibodies to bovine serum proteins in individual ponies. These antibodies were very transitory, usually lasting no longer than a week. Some horses, however, which had been given 4 vaccinations developed similar antibodies which persisted 3 months beyond the last vaccination. The extraneous precipitin lines produced by these antibodies in the AGID test for EIA were readily distinguished from true EIA-associated reactions and did not result in false-positive interpretations of the test. However, heavy percipitin lines due to strong antibovine serum activity did mask weakly positive EIA reactions.", "contents": "Equine antibody to bovine serum induced by several equine vaccines as a source of extraneous precipitin lines in the agar gel immunodiffusion test for equine infectious anemia. Precipitin lines not associated with equine infectious anemia (EIA) were observed in routine agar gel immunodiffusion (AGID) testing for the infection. The serums which produced these lines were obtained from horses which had been given multiple vaccinations with commercially available cell culture-origin equine virus vaccines as part of a comprehensive herd health program. The lines formed against cell culture-derived, but not spleen-derived EIA viral antigens. Investigation revealed that bovine serum proteins in the vaccines induced precipitating antibodies which reacted with bovine serum proteins in cell culture-derived antigens. A vaccination trial, utilizing 4 commercially available vaccines in various combinations, indicated that as few as 2 vaccinations could induce AGID-detectable antibodies to bovine serum proteins in individual ponies. These antibodies were very transitory, usually lasting no longer than a week. Some horses, however, which had been given 4 vaccinations developed similar antibodies which persisted 3 months beyond the last vaccination. The extraneous precipitin lines produced by these antibodies in the AGID test for EIA were readily distinguished from true EIA-associated reactions and did not result in false-positive interpretations of the test. However, heavy percipitin lines due to strong antibovine serum activity did mask weakly positive EIA reactions."}
{"id": "PMID:192112", "title": "Nonlethal experimental inoculation of Columbia black-tailed deer (Odocoileus hemionus columbianus) with virus of epizootic hemorrhagic deer disease.", "content": "Intramuscular or intravenous inoculation of 5 Columbia black-tailed deer (Odocoileus hemionus columbianus) with virus of epizootic hemorrhagic deer disease (EHD) did not produce overt clinical disease. Two white-tailed deer (Odocoileus virginianus) exposed identically died in 5 to 6 days. There were no significant lesions in 1 black-tailed deer euthanatized on postinoculation day 5. The EHd virus was not isolated from the spleen of that deer. Seroconversion occurred in black-tailed deer, from zero EHD virus antibody titer before inoculation to titers of 1:128 to 1:256 after inoculation.", "contents": "Nonlethal experimental inoculation of Columbia black-tailed deer (Odocoileus hemionus columbianus) with virus of epizootic hemorrhagic deer disease. Intramuscular or intravenous inoculation of 5 Columbia black-tailed deer (Odocoileus hemionus columbianus) with virus of epizootic hemorrhagic deer disease (EHD) did not produce overt clinical disease. Two white-tailed deer (Odocoileus virginianus) exposed identically died in 5 to 6 days. There were no significant lesions in 1 black-tailed deer euthanatized on postinoculation day 5. The EHd virus was not isolated from the spleen of that deer. Seroconversion occurred in black-tailed deer, from zero EHD virus antibody titer before inoculation to titers of 1:128 to 1:256 after inoculation."}
{"id": "PMID:192113", "title": "Demonstration and quantitation of immunoglobulins in bovine serum, follicular fluid, and uterine and vaginal secretions with reference to bovine viral diarrhea and infectious bovine rhinotracheitis.", "content": "Immunoglobulin concentrations (IgG, IgM, and IgA) in bovine serum, follicular fluid, and uterine and vaginal secretions were determined. The specificities of IgG, IgM, and IgA for virus-neutralizing antibody against bovine viral diarrhea (BVD) and infectious bovine rhinotracheitis (IBR) viruses were also examined. High concentrations of IgG were present in both serum and follicular fluid. The IgG, IgM, and IgA concentrations were low in uterine and vaginal secretions. There was more IgG in the uterus during estrus than at any other time. Virus-neutralizing antibodies against BVD and IBR in serum of cows were mainly the IgG class. There was positive correlation between serum and follicular fluid virus-neutralizing antibody titers fro BVD and IBR. These antibodies may provide some protection for recently ovulated ova.", "contents": "Demonstration and quantitation of immunoglobulins in bovine serum, follicular fluid, and uterine and vaginal secretions with reference to bovine viral diarrhea and infectious bovine rhinotracheitis. Immunoglobulin concentrations (IgG, IgM, and IgA) in bovine serum, follicular fluid, and uterine and vaginal secretions were determined. The specificities of IgG, IgM, and IgA for virus-neutralizing antibody against bovine viral diarrhea (BVD) and infectious bovine rhinotracheitis (IBR) viruses were also examined. High concentrations of IgG were present in both serum and follicular fluid. The IgG, IgM, and IgA concentrations were low in uterine and vaginal secretions. There was more IgG in the uterus during estrus than at any other time. Virus-neutralizing antibodies against BVD and IBR in serum of cows were mainly the IgG class. There was positive correlation between serum and follicular fluid virus-neutralizing antibody titers fro BVD and IBR. These antibodies may provide some protection for recently ovulated ova."}
{"id": "PMID:192114", "title": "The relationship between nicotinamide adenine dinucleotide concentration and antibacterial activity of isoniazid in Mycobacterium tuberculosis.", "content": "The relationship between the antibacterial effect of isoniazid and the intracellular concentration of nicotinamide adenine dinucleotide (NAD) was investigated in Mycobacterium tuberculosis strain H37Rv given continuous and pulsed exposures to the drug. Depletion of NAD to a plateau value occurred rapidly during exposure, and recovery after a pulse of isoniazid was also rapid. It seemed unlikely that NAD depletion was the direct cause of the antibacterial activity because (1) insufficient depletion occurred at low isoniazid concentrations; (2) antibacterial activity, but not NAD depletion, was proportional to the product of isoniazid concentration and the exposure period; and (3) NAD depletion was not related to antibacterial activity in cultures of differing physiologic state.", "contents": "The relationship between nicotinamide adenine dinucleotide concentration and antibacterial activity of isoniazid in Mycobacterium tuberculosis. The relationship between the antibacterial effect of isoniazid and the intracellular concentration of nicotinamide adenine dinucleotide (NAD) was investigated in Mycobacterium tuberculosis strain H37Rv given continuous and pulsed exposures to the drug. Depletion of NAD to a plateau value occurred rapidly during exposure, and recovery after a pulse of isoniazid was also rapid. It seemed unlikely that NAD depletion was the direct cause of the antibacterial activity because (1) insufficient depletion occurred at low isoniazid concentrations; (2) antibacterial activity, but not NAD depletion, was proportional to the product of isoniazid concentration and the exposure period; and (3) NAD depletion was not related to antibacterial activity in cultures of differing physiologic state."}
{"id": "PMID:192115", "title": "Generalized amyloid in a family of Swedish origin. A study of 426 family members in seven generations of a new kinship with neuropathy, nephropathy, and central nervous system involvement.", "content": "We report a new kinship with systemic amyloid presenting as peripheral neuropathy in the fourth and fifth decades of life. A progressive sensory and motor loss starting in the lower extremities occurs from this disease, and there is subsequent renal, cardiac, gastrointestinal, ocular, and cutaneous involvement. Histologic studies show that amyloid deposition is mainly in connective tissue structures; there is an unusual infiltration of the meninges and central nervous system. Review of records of 426 family members in seven generations showed that this disease is inherited as an autosomal dominant. The absence of immunoglobulin disorders in two affected family members studied in depth suggests that this is not the primary type of amyloid in which the deposits are composed of fragments of immunoglobulin light chains. Similarly the absence of elevated levels of protein SAA (the serum precursor of secondary amyloid) suggests that this is not a secondary form of amyloid.", "contents": "Generalized amyloid in a family of Swedish origin. A study of 426 family members in seven generations of a new kinship with neuropathy, nephropathy, and central nervous system involvement. We report a new kinship with systemic amyloid presenting as peripheral neuropathy in the fourth and fifth decades of life. A progressive sensory and motor loss starting in the lower extremities occurs from this disease, and there is subsequent renal, cardiac, gastrointestinal, ocular, and cutaneous involvement. Histologic studies show that amyloid deposition is mainly in connective tissue structures; there is an unusual infiltration of the meninges and central nervous system. Review of records of 426 family members in seven generations showed that this disease is inherited as an autosomal dominant. The absence of immunoglobulin disorders in two affected family members studied in depth suggests that this is not the primary type of amyloid in which the deposits are composed of fragments of immunoglobulin light chains. Similarly the absence of elevated levels of protein SAA (the serum precursor of secondary amyloid) suggests that this is not a secondary form of amyloid."}
{"id": "PMID:192118", "title": "[Purification and some properties of \"Clostridium perfringens\" delta toxin (author's transl)].", "content": "Delta toxin, a hemolytic exocellular protein excreted by C. perfringens type C has been purified to homogeneity, assessed by polyacrylamide disc gel electrophoresis. Purification steps involved successively calcium phosphate gel formation in culture supernatant fluid, salting-out of unadsorbed material by ammonium sulfate to 50 % saturation, isoelectric focusing and gel filtration on Sephadex G75. Purified toxin appears as a basic protein occuring in two forms with isoelectric points of 8.8 and 9.4 as disclosed by isoelectric focusing. Molecular weight estimated by SDS-polyacrylamide disc gel electrophoresis was found to be close to 42,000 for the two forms. The lytic activity of delta toxin is inhibited by Ca++ and EDTA. The toxin is activated by short-term treatment with low concentration of trypsin.", "contents": "[Purification and some properties of \"Clostridium perfringens\" delta toxin (author's transl)]. Delta toxin, a hemolytic exocellular protein excreted by C. perfringens type C has been purified to homogeneity, assessed by polyacrylamide disc gel electrophoresis. Purification steps involved successively calcium phosphate gel formation in culture supernatant fluid, salting-out of unadsorbed material by ammonium sulfate to 50 % saturation, isoelectric focusing and gel filtration on Sephadex G75. Purified toxin appears as a basic protein occuring in two forms with isoelectric points of 8.8 and 9.4 as disclosed by isoelectric focusing. Molecular weight estimated by SDS-polyacrylamide disc gel electrophoresis was found to be close to 42,000 for the two forms. The lytic activity of delta toxin is inhibited by Ca++ and EDTA. The toxin is activated by short-term treatment with low concentration of trypsin."}
{"id": "PMID:192119", "title": "Fibrous histiocytoma of the subglottic larynx.", "content": "Histiocytic tumors are being reported with increasing frequency in the medical literature. In spite of confusion regarding nomenclature, appropriate diagnostic and treatment modalities exist. A malignant fibrous histiocytoma of the subglottic larynx is reported. Discussion of the present criteria for a diagnosis of malignancy and a rationale of treatment is presented.", "contents": "Fibrous histiocytoma of the subglottic larynx. Histiocytic tumors are being reported with increasing frequency in the medical literature. In spite of confusion regarding nomenclature, appropriate diagnostic and treatment modalities exist. A malignant fibrous histiocytoma of the subglottic larynx is reported. Discussion of the present criteria for a diagnosis of malignancy and a rationale of treatment is presented."}
{"id": "PMID:192123", "title": "The role of metals in enzyme activity.", "content": "Metal ions play important roles in the biological function of many enzymes. The various modes of metal-protein interaction include metal-, ligand-, and enzyme-bridge complexes. Metals can serve as electron donors or acceptors, Lewis acids or structural regulators. Those that participate directly in the catalytic mechanism usually exhibit anomalous physicochemical characteristics reflecting their entatic state. Carboxypeptidase A, liver alcohol dehydrogenase, aspartate transcarbamoylase and alkaline phosphatase exemplify the different roles of metals in metalloenzymes while the nucleotide polymerases point to the essential role of zinc in maintaining normal growth and development.", "contents": "The role of metals in enzyme activity. Metal ions play important roles in the biological function of many enzymes. The various modes of metal-protein interaction include metal-, ligand-, and enzyme-bridge complexes. Metals can serve as electron donors or acceptors, Lewis acids or structural regulators. Those that participate directly in the catalytic mechanism usually exhibit anomalous physicochemical characteristics reflecting their entatic state. Carboxypeptidase A, liver alcohol dehydrogenase, aspartate transcarbamoylase and alkaline phosphatase exemplify the different roles of metals in metalloenzymes while the nucleotide polymerases point to the essential role of zinc in maintaining normal growth and development."}
{"id": "PMID:192124", "title": "Crystalline muscle inclusions in atypical postinfectious polyradiculoneuropathy.", "content": "Crystalline inclusions were found in the muscle of a previously healthy 63 year old male with atypical postinfectious polyradiculoneuropathy. Approximately 12 days after the onset of the illness, biopsy of biceps femoris and vastus lateralis muscles revealed, in addition to changes consistent with early neurogenic atrophy, inclusions measuring 22 micronm in greatest dimensions. In plastic-embedded toluidine blue stained sections the translucent ovoid to angular inclusions were seen in a subsarcolemmal position, adjacent to nuclei. Ultrastructural examination revealed a crystalline structure consisting of parallel dense lines measuring approximately 70 A in diameter with an axial periodicity of 130 A. Unlike rods, the crystalline inclusions were not continuous with Z-discs; rather they displaced contractile and other cellular elements. Their appearance was similar to intramuscular crystals in diabetic amyotrophy and to vincristine-induced and naturally occurring intracytoplasmic crystalline structures. The nature of the crystalline inclusions and their relationship to the basic disease process was not established.", "contents": "Crystalline muscle inclusions in atypical postinfectious polyradiculoneuropathy. Crystalline inclusions were found in the muscle of a previously healthy 63 year old male with atypical postinfectious polyradiculoneuropathy. Approximately 12 days after the onset of the illness, biopsy of biceps femoris and vastus lateralis muscles revealed, in addition to changes consistent with early neurogenic atrophy, inclusions measuring 22 micronm in greatest dimensions. In plastic-embedded toluidine blue stained sections the translucent ovoid to angular inclusions were seen in a subsarcolemmal position, adjacent to nuclei. Ultrastructural examination revealed a crystalline structure consisting of parallel dense lines measuring approximately 70 A in diameter with an axial periodicity of 130 A. Unlike rods, the crystalline inclusions were not continuous with Z-discs; rather they displaced contractile and other cellular elements. Their appearance was similar to intramuscular crystals in diabetic amyotrophy and to vincristine-induced and naturally occurring intracytoplasmic crystalline structures. The nature of the crystalline inclusions and their relationship to the basic disease process was not established."}
{"id": "PMID:192125", "title": "Determination of liver microsomal glucose-6-phosphatase.", "content": "A procedure for the determination of liver microsomal glucose-6-phosphatase is described. Homogenization and ultracentrifrigation were used to prepare a precipitate whose character was defined by monitoring the desire enzyme activity which serves as a marker. Activity of the enzyme was determined by means of a sensitive colorimetric reaction for the product, inorganic phosphate. Non-enzymatic hydrolysis problems with the substrate are minimized in this procedure by the masking action of citrate. The final heteropoly blue color appears to be considerably sensitized by interaction of phosphomolybdous ion with arsenite. The stability of the relatively labile enzyme was ensured by chelating any metals present with ethylene diamine tetraacetic acid. The overall results obtained by the procedure appear to be useful as an aid in the diagnosis of Type I glycogenosis, a glycogen storage disease called Von Gierke's disease.", "contents": "Determination of liver microsomal glucose-6-phosphatase. A procedure for the determination of liver microsomal glucose-6-phosphatase is described. Homogenization and ultracentrifrigation were used to prepare a precipitate whose character was defined by monitoring the desire enzyme activity which serves as a marker. Activity of the enzyme was determined by means of a sensitive colorimetric reaction for the product, inorganic phosphate. Non-enzymatic hydrolysis problems with the substrate are minimized in this procedure by the masking action of citrate. The final heteropoly blue color appears to be considerably sensitized by interaction of phosphomolybdous ion with arsenite. The stability of the relatively labile enzyme was ensured by chelating any metals present with ethylene diamine tetraacetic acid. The overall results obtained by the procedure appear to be useful as an aid in the diagnosis of Type I glycogenosis, a glycogen storage disease called Von Gierke's disease."}
{"id": "PMID:192126", "title": "[Action of distension upon uterine growth (author's transl)].", "content": "The uterine horn growth has been studied in castrated female rats under the influence of distension. One of the two horns was used as a control horn, to insure us that no endogenous hormone was responsible for the uterine growth. Morphological studies, as well at low as at high resolution, demonstrated the ability of distension to initiate an epithelial growth. The use of 3H thymidine, or H3 uridine also provided some evidence for RNA synthesis 30 mm after distension initiation, and DNA synthesis 24 to 48 hours after distension onset. In these cases all the uterine tissues were concerned.", "contents": "[Action of distension upon uterine growth (author's transl)]. The uterine horn growth has been studied in castrated female rats under the influence of distension. One of the two horns was used as a control horn, to insure us that no endogenous hormone was responsible for the uterine growth. Morphological studies, as well at low as at high resolution, demonstrated the ability of distension to initiate an epithelial growth. The use of 3H thymidine, or H3 uridine also provided some evidence for RNA synthesis 30 mm after distension initiation, and DNA synthesis 24 to 48 hours after distension onset. In these cases all the uterine tissues were concerned."}
{"id": "PMID:192131", "title": "[Immunoglobulins and sheep red cell receptors in human lymphoblastoid cell lines simultaneously carrying Epstein-Barr virus and cytomegalovirus genomes].", "content": "In this communication we attempt to characterize the principal immunological properties of 3 human lymphoblastoid cell lines (LCL) established in our laboratory which carry both the EBV and CMV genomes. The data obtained suggests that two LCL are representative of B lymphocytes while the other LCL has a mixed cell population with the majority being of the B type. The reasons for this heterogeneity are discussed. It is suggested that CMV may also transform thymus-independent (B) lymphocytes.", "contents": "[Immunoglobulins and sheep red cell receptors in human lymphoblastoid cell lines simultaneously carrying Epstein-Barr virus and cytomegalovirus genomes]. In this communication we attempt to characterize the principal immunological properties of 3 human lymphoblastoid cell lines (LCL) established in our laboratory which carry both the EBV and CMV genomes. The data obtained suggests that two LCL are representative of B lymphocytes while the other LCL has a mixed cell population with the majority being of the B type. The reasons for this heterogeneity are discussed. It is suggested that CMV may also transform thymus-independent (B) lymphocytes."}
{"id": "PMID:192133", "title": "[Interferon inhibition of lymphocyte mitogenesis].", "content": "Interferon inhibits the early phase of mitogenic action of concanavalin A on lymphocytes. There was no evidence for a role of cyclic AMP in the process of inhibition. Dialysis of interferon against high salt and urea did not separate cell inhibitory activity from antiviral activity.", "contents": "[Interferon inhibition of lymphocyte mitogenesis]. Interferon inhibits the early phase of mitogenic action of concanavalin A on lymphocytes. There was no evidence for a role of cyclic AMP in the process of inhibition. Dialysis of interferon against high salt and urea did not separate cell inhibitory activity from antiviral activity."}
{"id": "PMID:192134", "title": "[Monoclonal immunoglobulins, cytomegalovirus infection and malignant observations blood diseases].", "content": "Monoclonal immunoglobulins (Eg) are detected in the serum of 7/29 patients treated for leukemia (6 cases) or lymphoma (1 case). All of them developped cytomegalovirus (CMV) infection. The 7 patients were children or young adults; 6/7 were in complete remission of the hematological disease. They completed chemotherapy before the onset of the viral infection and had received blood components. The monoclonal Ig are IgG (6 cases) and IgM (1 case), In 2 sera there are two M components. The level of the peak was under 1 g/100 ml (5 cases) and reached 1.5 and 1.7 g/100 ml in the 2 other sera. Polyclonal Ig are normal except in one case where there is moderate hypo-Ig; Plasmocytic infiltration was observed in none of the 7 patients. Evidence of CMV infection was confirmed by viremia and/or significant rise of complement fixing antibodies. In four cases, the monoclonal Ig disappeared in less than 6 months. The significance of the monoclonal Ig associated with CMV infection is discussed.", "contents": "[Monoclonal immunoglobulins, cytomegalovirus infection and malignant observations blood diseases]. Monoclonal immunoglobulins (Eg) are detected in the serum of 7/29 patients treated for leukemia (6 cases) or lymphoma (1 case). All of them developped cytomegalovirus (CMV) infection. The 7 patients were children or young adults; 6/7 were in complete remission of the hematological disease. They completed chemotherapy before the onset of the viral infection and had received blood components. The monoclonal Ig are IgG (6 cases) and IgM (1 case), In 2 sera there are two M components. The level of the peak was under 1 g/100 ml (5 cases) and reached 1.5 and 1.7 g/100 ml in the 2 other sera. Polyclonal Ig are normal except in one case where there is moderate hypo-Ig; Plasmocytic infiltration was observed in none of the 7 patients. Evidence of CMV infection was confirmed by viremia and/or significant rise of complement fixing antibodies. In four cases, the monoclonal Ig disappeared in less than 6 months. The significance of the monoclonal Ig associated with CMV infection is discussed."}
{"id": "PMID:192137", "title": "Mechanisms of hepatic bile formation.", "content": "It should be evident from this review of recent investigations that we are still very far from a consistent description of bile formation, much less a satisfactory understanding. Nevertheless certain broad conclusions emerge. Four distinct kinds of active solute transport can be identified, and because bile always has nearly the same osmotic pressure as plasma, each of them is a determinant of bile flow. 1. Concentrative transport of water-soluble organic constituents, of which bile acids are quantitatively most important, occurs in the canaliculi accompanied by the passive flow of water and inorganic electrolytes. Owing to micelle formation the osmotic force for this flow is largely attributable to Na+ ions that accompany the bile acids anions. 2. The canalicular flow obligated by the excretion of bile acids is supplemented by the entry of additional fluid, the so-called bile acid-independent canalicular fraction. Because no organic component has been identified to account for this phenomenon, the active transport of one or more inorganic ions is probably responsible. The limited evidence available at present suggests that Na+ ions is the most likely candidate. 3. The extralobular biliary epithelium can modify the flow and composition of bile by the reabsorption of inorganic ions--a process which resembles reabsorption from the gallbladder in the sense that bile in the lumen remains iso-osmotic with plasma while bile acids and the other organic constituents are concentrated. 4. Under the influence of secretin, and to a lesser degree other intestinal hormones, the ducts or ductules can secrete additional fluid in which HCO3- is concentrated with respect to plasma. A fifth component of bile is generated by the canalicular excretion of phospholipid and cholesterol, but these are insoluble in water and are incorporated into micelles, and, therefore exert no osmotic force. The existence of these processes is inferred from studies of many different species, and it should be emphasized that the picture is a composite one. For example, distal fluid reabsorption has been convincingly demonstrated only in dogs and monkeys, and secretin is not a choleretic in rats or rabbits. It should also be clear that the actual mechanisms of solute transport remain poorly defined. Thus the term active transport in the present context should be thought of in its general thermodynamic sense rather than as denoting any particular transport mechanism. For the future, the most pressing problems are methodologic. To mention only three that seem especially important: ways must be found to sample bile closer to its origin; the proper interpretation of studies with isolated liver cell membranes will require unambiguous methods to certify their source; and descriptions of transport kinetics must somehow be refined to reflect the effective intracellular concentration of solutes as well as their distribution within the liver lobule.", "contents": "Mechanisms of hepatic bile formation. It should be evident from this review of recent investigations that we are still very far from a consistent description of bile formation, much less a satisfactory understanding. Nevertheless certain broad conclusions emerge. Four distinct kinds of active solute transport can be identified, and because bile always has nearly the same osmotic pressure as plasma, each of them is a determinant of bile flow. 1. Concentrative transport of water-soluble organic constituents, of which bile acids are quantitatively most important, occurs in the canaliculi accompanied by the passive flow of water and inorganic electrolytes. Owing to micelle formation the osmotic force for this flow is largely attributable to Na+ ions that accompany the bile acids anions. 2. The canalicular flow obligated by the excretion of bile acids is supplemented by the entry of additional fluid, the so-called bile acid-independent canalicular fraction. Because no organic component has been identified to account for this phenomenon, the active transport of one or more inorganic ions is probably responsible. The limited evidence available at present suggests that Na+ ions is the most likely candidate. 3. The extralobular biliary epithelium can modify the flow and composition of bile by the reabsorption of inorganic ions--a process which resembles reabsorption from the gallbladder in the sense that bile in the lumen remains iso-osmotic with plasma while bile acids and the other organic constituents are concentrated. 4. Under the influence of secretin, and to a lesser degree other intestinal hormones, the ducts or ductules can secrete additional fluid in which HCO3- is concentrated with respect to plasma. A fifth component of bile is generated by the canalicular excretion of phospholipid and cholesterol, but these are insoluble in water and are incorporated into micelles, and, therefore exert no osmotic force. The existence of these processes is inferred from studies of many different species, and it should be emphasized that the picture is a composite one. For example, distal fluid reabsorption has been convincingly demonstrated only in dogs and monkeys, and secretin is not a choleretic in rats or rabbits. It should also be clear that the actual mechanisms of solute transport remain poorly defined. Thus the term active transport in the present context should be thought of in its general thermodynamic sense rather than as denoting any particular transport mechanism. For the future, the most pressing problems are methodologic. To mention only three that seem especially important: ways must be found to sample bile closer to its origin; the proper interpretation of studies with isolated liver cell membranes will require unambiguous methods to certify their source; and descriptions of transport kinetics must somehow be refined to reflect the effective intracellular concentration of solutes as well as their distribution within the liver lobule."}
{"id": "PMID:192132", "title": "[Tumour antigens inducing immune reactions].", "content": "Antigens of viral tumours are the same for all the tumours due to the same virus. Antibodies in tumours bearing animals allow to detect antigens in nucleus, in cytoplasm and on the cell membrane which carries also embryonic antigens and the antigen responsible for tumour rejection by sensitized lymphcytes (TSTA or TATA). Is this antigen identical to the surface antigen shown by antibodies? Purification of membrane antigens will answer this important question. Chemically induced tumours bear tumour rejection antigens having an individual specificity, perhaps related to modified histocompatibility antigens, and embryonic antigens. Both give rise to antibodies and sensitized lymphocytes. Among human tumours, Burkitt lymphoma is strongly antigenic. Its viral origin is highly likely. Antibodies in sera of Burkitt patients react with antigens present in nucleus, cytoplasm and on the membrane of malignant or transformed cells. Sensitized lymphocytes in the peripheral blood recognize a membrane antigen probably different of that revealed by antibodies. Antibodies found in sera of patients with carcinoma react mainly with tissular antigens. In these cases, methods exploring delayed type reactivity, such as leukocyte migration inhibition and moreover skin testing with tumour extracts, gave some promising results.", "contents": "[Tumour antigens inducing immune reactions]. Antigens of viral tumours are the same for all the tumours due to the same virus. Antibodies in tumours bearing animals allow to detect antigens in nucleus, in cytoplasm and on the cell membrane which carries also embryonic antigens and the antigen responsible for tumour rejection by sensitized lymphcytes (TSTA or TATA). Is this antigen identical to the surface antigen shown by antibodies? Purification of membrane antigens will answer this important question. Chemically induced tumours bear tumour rejection antigens having an individual specificity, perhaps related to modified histocompatibility antigens, and embryonic antigens. Both give rise to antibodies and sensitized lymphocytes. Among human tumours, Burkitt lymphoma is strongly antigenic. Its viral origin is highly likely. Antibodies in sera of Burkitt patients react with antigens present in nucleus, cytoplasm and on the membrane of malignant or transformed cells. Sensitized lymphocytes in the peripheral blood recognize a membrane antigen probably different of that revealed by antibodies. Antibodies found in sera of patients with carcinoma react mainly with tissular antigens. In these cases, methods exploring delayed type reactivity, such as leukocyte migration inhibition and moreover skin testing with tumour extracts, gave some promising results."}
{"id": "PMID:192141", "title": "[Superinduction of interferon and and a study of its messenger RNA].", "content": "Combined use of interferon inductor poly-IC and antibiotics (cycloheximide and actinomycin D) provided a significant increase (up to 1000 times) in interferon production by chick, mouse, monkey and human cells. Messenger RNA with matrix activity for interferon (mRNA-IF) was isolated from superinduced cells. On translation of mRNA-IF in homogenous and heterogenous cells the specificity of interferons produced was determined by the type of the cells from which mRNA-IF was isolated. Sedimentation analysis of various mRNA-IF revealed 2 peaks of activity: major (5--15S) and minor (25--30S).", "contents": "[Superinduction of interferon and and a study of its messenger RNA]. Combined use of interferon inductor poly-IC and antibiotics (cycloheximide and actinomycin D) provided a significant increase (up to 1000 times) in interferon production by chick, mouse, monkey and human cells. Messenger RNA with matrix activity for interferon (mRNA-IF) was isolated from superinduced cells. On translation of mRNA-IF in homogenous and heterogenous cells the specificity of interferons produced was determined by the type of the cells from which mRNA-IF was isolated. Sedimentation analysis of various mRNA-IF revealed 2 peaks of activity: major (5--15S) and minor (25--30S)."}
{"id": "PMID:192142", "title": "Comparative study of the antiviral activity of acyl derivatives of 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine and other nucleosides against encephalitis in mice.", "content": "Anti-deoxyribonucleic acid virus activities of 3'-O-acyl derivatives of 2,2'-anhydro-1-beta-d-arabinofuranosyl cytosine (cyclo-C) and 1-beta-d-arabinofuranosylcytosine (Ara-C) were evaluated by using an in vivo test system in mice. Among the derivatives tested, 3'-O-decanoyl cyclo-C hydrochloride was the most effective against herpes simplex virus-induced encephalitis in mice when the drug was administered directly into infected brains of mice (target-organ treatment). A comparative study of the treatment of herpetic encephalitis in mice with 3'O-decanoyl cyclo-C and other nucleosides, including Ara-C, 9-beta-d-arabinofuranosyladenine (Ara-A), and 5-iodo-2'-deoxyrudine (IUdR), proved Ara-A to be more efficacious than the other nucleosides, followed by 3'-O-decanoyl cyclo-C, which was more active than Ara-C and IUdR. Administration of 3'-O-acyl cyclo-C's by intraperitoneal injection, however, failed to demonstrate activity against herpetic encephalitis in mice. The antivaccinial activity of 3'-O-decanoyl cyclo-C was also compared with that of other compounds against encephalitis and dermal tail lesions in mice caused by vaccinia virus infection. Interaperitoneally administered 3'-O-decanoyl cyclo-C and Ara-C also showed no significant activity against the diseases. Under these test conditions, N-methylisatin-beta-thiosemicarbazone (Marboran) was the most active compound, followed by Ara-A.", "contents": "Comparative study of the antiviral activity of acyl derivatives of 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine and other nucleosides against encephalitis in mice. Anti-deoxyribonucleic acid virus activities of 3'-O-acyl derivatives of 2,2'-anhydro-1-beta-d-arabinofuranosyl cytosine (cyclo-C) and 1-beta-d-arabinofuranosylcytosine (Ara-C) were evaluated by using an in vivo test system in mice. Among the derivatives tested, 3'-O-decanoyl cyclo-C hydrochloride was the most effective against herpes simplex virus-induced encephalitis in mice when the drug was administered directly into infected brains of mice (target-organ treatment). A comparative study of the treatment of herpetic encephalitis in mice with 3'O-decanoyl cyclo-C and other nucleosides, including Ara-C, 9-beta-d-arabinofuranosyladenine (Ara-A), and 5-iodo-2'-deoxyrudine (IUdR), proved Ara-A to be more efficacious than the other nucleosides, followed by 3'-O-decanoyl cyclo-C, which was more active than Ara-C and IUdR. Administration of 3'-O-acyl cyclo-C's by intraperitoneal injection, however, failed to demonstrate activity against herpetic encephalitis in mice. The antivaccinial activity of 3'-O-decanoyl cyclo-C was also compared with that of other compounds against encephalitis and dermal tail lesions in mice caused by vaccinia virus infection. Interaperitoneally administered 3'-O-decanoyl cyclo-C and Ara-C also showed no significant activity against the diseases. Under these test conditions, N-methylisatin-beta-thiosemicarbazone (Marboran) was the most active compound, followed by Ara-A."}
{"id": "PMID:192143", "title": "Experimental herpes simplex virus type 1 encephalitis: treatment with 5-trifluoromethyl-2'-deoxyuridine.", "content": "5-Trifluoromethyl-2'-deoxyuridine (F(3)dThd) was evaluated for its neurotoxicity and for its ability to increase the life span of mice injected intracerebrally with herpes simplex virus type 1 (HSV-1) and F(3)dThd simultaneously. F(3)dThd showed no neurotoxicity at the highest concentration tested (100 mg/kg). Mice injected intracerebrally with HSV-1 died within 5 days postinfection. However, all mice injected concurrently with HSV-1 and 100 mg of F(3)dThd per kg lived through the termination of the experiment (60 days). Protection of mice from HSV-1 encephalitis by F(3)dThd has been shown to be dose dependent, with 100, 75, 50, and 25 mg of F(3)dThd per kg yielding a survival rate of 100, 90, 50, and 10%, respectively. HSV-1 titers in mouse brains receiving HSV-1 and 100 mg of F(3)dThd per kg concurrently were 100- to 1,000-fold lower at 2 to 4 days postinfection than control mice receiving HSV-1 alone. F(3)dThd was shown not to stimulate interferon production. Encephalitis caused by a ribonucleic acid virus, encephalomyocarditis virus, was not modified by F(3)dThd treatment.", "contents": "Experimental herpes simplex virus type 1 encephalitis: treatment with 5-trifluoromethyl-2'-deoxyuridine. 5-Trifluoromethyl-2'-deoxyuridine (F(3)dThd) was evaluated for its neurotoxicity and for its ability to increase the life span of mice injected intracerebrally with herpes simplex virus type 1 (HSV-1) and F(3)dThd simultaneously. F(3)dThd showed no neurotoxicity at the highest concentration tested (100 mg/kg). Mice injected intracerebrally with HSV-1 died within 5 days postinfection. However, all mice injected concurrently with HSV-1 and 100 mg of F(3)dThd per kg lived through the termination of the experiment (60 days). Protection of mice from HSV-1 encephalitis by F(3)dThd has been shown to be dose dependent, with 100, 75, 50, and 25 mg of F(3)dThd per kg yielding a survival rate of 100, 90, 50, and 10%, respectively. HSV-1 titers in mouse brains receiving HSV-1 and 100 mg of F(3)dThd per kg concurrently were 100- to 1,000-fold lower at 2 to 4 days postinfection than control mice receiving HSV-1 alone. F(3)dThd was shown not to stimulate interferon production. Encephalitis caused by a ribonucleic acid virus, encephalomyocarditis virus, was not modified by F(3)dThd treatment."}
{"id": "PMID:192144", "title": "Amorphous ferrous sulfide as a reducing agent for culture of anaerobes.", "content": "Amorphous ferrous sulfide, prepared by reacting ferrous ammonium sulfate and sodium sulfide, is an excellent reducing agent for the culture of anaerobes. It reduces resazurin and reacts much more rapidly with O2 than does either soluble sulfide (HS)- or cysteine. One of the end products of the oxidation of ferrous sulfide with O2 is red and serves as an indicator for the oxygen contamination of a culture medium. Amorphous ferrous sulfide served as a suitable reducing agent for the growth of species of Methanobacterium or Clostridium. Its use is recommended for enrichment or culture of anaerobes (e.g. autotrophs, fermentative organisms) from sediments and other habitats were organic reducing agents are undesirable and where soluble sulfide might be toxic.", "contents": "Amorphous ferrous sulfide as a reducing agent for culture of anaerobes. Amorphous ferrous sulfide, prepared by reacting ferrous ammonium sulfate and sodium sulfide, is an excellent reducing agent for the culture of anaerobes. It reduces resazurin and reacts much more rapidly with O2 than does either soluble sulfide (HS)- or cysteine. One of the end products of the oxidation of ferrous sulfide with O2 is red and serves as an indicator for the oxygen contamination of a culture medium. Amorphous ferrous sulfide served as a suitable reducing agent for the growth of species of Methanobacterium or Clostridium. Its use is recommended for enrichment or culture of anaerobes (e.g. autotrophs, fermentative organisms) from sediments and other habitats were organic reducing agents are undesirable and where soluble sulfide might be toxic."}
{"id": "PMID:192145", "title": "Regeneration of pleated filters used to concentrate enteroviruses from large volumes of tap water.", "content": "Pleated cartridge filters are capable of concentrating enteroviruses from large volumes (well over 2,000 liters) of tap water. These epoxy-fiberglass filters can be regenerated if they are treated with 0.1 N NaOH or autoclaved to inactivate any contaminating virus. The regenerated filters regained their ability to concentrate viruses from water at high flow rates.", "contents": "Regeneration of pleated filters used to concentrate enteroviruses from large volumes of tap water. Pleated cartridge filters are capable of concentrating enteroviruses from large volumes (well over 2,000 liters) of tap water. These epoxy-fiberglass filters can be regenerated if they are treated with 0.1 N NaOH or autoclaved to inactivate any contaminating virus. The regenerated filters regained their ability to concentrate viruses from water at high flow rates."}
{"id": "PMID:192146", "title": "Inactivation of polioviruses and coxsackieviruses in surface water.", "content": "Inactivation rates of polioviruses 1 and 3 and coxsackieviruses A-13 and B-1 were determined in situ in the Rio Grande in southern New Mexico, using membrane dialysis chambers. Inactivation of the viruses was exponential, and the rates of inactivation were apparently affected principally by the water temperature. Stability of the viruses in river water differed, with poliovirus 1 and coxsackie B-1 being most stable. Typically 1-log reductions of infectivity at water temperatures ranging between 23 and 27 degrees C required 25 h for poliovirus 1, 19 h for poliovirus 3, and 7 h for coxsackie virus A-13. At water temperatures of 4 to 8 degrees C, the log reduction times for poliovirus 1 and coxsackievirus B-1 were 46 and 58 h, respectively. Results obtained with labeled poliovirus 1 and coxsackievirus B-1 and with infectious ribonucleic acid indicate that inactivation was due to damage to viral ribonucleic acid. Virus-inactivation rates were also affected by heat sterilization of river water, indicating the presence of a heat-labile or volatile inactivating factor. The inactivating factor in Rio Grande water was apparently present at a constant concentration over a 1-year period.", "contents": "Inactivation of polioviruses and coxsackieviruses in surface water. Inactivation rates of polioviruses 1 and 3 and coxsackieviruses A-13 and B-1 were determined in situ in the Rio Grande in southern New Mexico, using membrane dialysis chambers. Inactivation of the viruses was exponential, and the rates of inactivation were apparently affected principally by the water temperature. Stability of the viruses in river water differed, with poliovirus 1 and coxsackie B-1 being most stable. Typically 1-log reductions of infectivity at water temperatures ranging between 23 and 27 degrees C required 25 h for poliovirus 1, 19 h for poliovirus 3, and 7 h for coxsackie virus A-13. At water temperatures of 4 to 8 degrees C, the log reduction times for poliovirus 1 and coxsackievirus B-1 were 46 and 58 h, respectively. Results obtained with labeled poliovirus 1 and coxsackievirus B-1 and with infectious ribonucleic acid indicate that inactivation was due to damage to viral ribonucleic acid. Virus-inactivation rates were also affected by heat sterilization of river water, indicating the presence of a heat-labile or volatile inactivating factor. The inactivating factor in Rio Grande water was apparently present at a constant concentration over a 1-year period."}
{"id": "PMID:192147", "title": "Degradation of malathion by salt-marsh microorganisms.", "content": "Numerous bacteria from a salt-marsh environment are capable of degrading malathion, an organophosphate insecticide, when supplied with additional nutrients as energy and carbon sources. Seven isolates exhibited ability (48 to 90%) to degrade malathion as a sole carbon source. Gas and thin-layer chromatography and infrared spectroscopy confirmed malathion to be degraded via malathion-monocarboxylic acid to the dicarboxylic acid and then to various phosphothionates. These techniques also identified desmethyl-malathion, phosphorthionates, and four-carbon dicarboxylic acids as degradation products formed as a result of phosphatase activity.", "contents": "Degradation of malathion by salt-marsh microorganisms. Numerous bacteria from a salt-marsh environment are capable of degrading malathion, an organophosphate insecticide, when supplied with additional nutrients as energy and carbon sources. Seven isolates exhibited ability (48 to 90%) to degrade malathion as a sole carbon source. Gas and thin-layer chromatography and infrared spectroscopy confirmed malathion to be degraded via malathion-monocarboxylic acid to the dicarboxylic acid and then to various phosphothionates. These techniques also identified desmethyl-malathion, phosphorthionates, and four-carbon dicarboxylic acids as degradation products formed as a result of phosphatase activity."}
{"id": "PMID:192148", "title": "Inactivation of clay-associated bacteriophage MS-2 by chlorine.", "content": "The model system consisted of bacteriophage MS-2, bentonite clay, and hypochlorous acid (HOC1). Factors that influenced association of the bacterial virus with bentonite were the titer of unadsorbed viruses, clay concentration, cation concentration, temperature, stirring rate, and the presence of soluble organics. Variation of the kinetic adsorption rate constant with stirring speed indicates that phage attachment is a diffusion-limited process; the attachment reaction has an apparent activation energy of 1 kcal/mol. About 18% of clay-associated bacteriophages was recovered by mixing the suspension with an organic eluent. Inactivation data were obtained from batch reactors operated under those conditions in which loss of HOC1 was minimal during the reaction. Bacteriophages attached to clay were more resistant to HOC1 than were freely suspended phages; for equivalent HOC1 concentrations, clay-associated phages required about twice the time that freely suspended phages required for loss of 99% of the initial virus titer.", "contents": "Inactivation of clay-associated bacteriophage MS-2 by chlorine. The model system consisted of bacteriophage MS-2, bentonite clay, and hypochlorous acid (HOC1). Factors that influenced association of the bacterial virus with bentonite were the titer of unadsorbed viruses, clay concentration, cation concentration, temperature, stirring rate, and the presence of soluble organics. Variation of the kinetic adsorption rate constant with stirring speed indicates that phage attachment is a diffusion-limited process; the attachment reaction has an apparent activation energy of 1 kcal/mol. About 18% of clay-associated bacteriophages was recovered by mixing the suspension with an organic eluent. Inactivation data were obtained from batch reactors operated under those conditions in which loss of HOC1 was minimal during the reaction. Bacteriophages attached to clay were more resistant to HOC1 than were freely suspended phages; for equivalent HOC1 concentrations, clay-associated phages required about twice the time that freely suspended phages required for loss of 99% of the initial virus titer."}
{"id": "PMID:192155", "title": "Autoimmune progesterone dermatitis.", "content": "Seven patients had autoimmune progesterone dermatitis. The morphological findings illustrate the polymorphous nature of the disease in which urticaria, erythema multiforme, and dyshidrosiform lesions were seen. Recurrence of the eruption five to ten days prior to the menses with spontaneous resolution following the menses was present in all cases. Intradermal skin testing to progesterone was done to confirm the diagnosis. Six of the seven patients has a history of use of artificial progestational hormones prior to the beginning of their eruption. It is postulated that the artificial progesterones may have been the trigger for the development of their autosensitivity. Treatment with conjugated estrogens resulted in remission of the disease in five of the seven cases reported.", "contents": "Autoimmune progesterone dermatitis. Seven patients had autoimmune progesterone dermatitis. The morphological findings illustrate the polymorphous nature of the disease in which urticaria, erythema multiforme, and dyshidrosiform lesions were seen. Recurrence of the eruption five to ten days prior to the menses with spontaneous resolution following the menses was present in all cases. Intradermal skin testing to progesterone was done to confirm the diagnosis. Six of the seven patients has a history of use of artificial progestational hormones prior to the beginning of their eruption. It is postulated that the artificial progesterones may have been the trigger for the development of their autosensitivity. Treatment with conjugated estrogens resulted in remission of the disease in five of the seven cases reported."}
{"id": "PMID:192160", "title": "The effect of methysergide and other receptor antagonists on fenfluramine-induced glucose uptake into the isolated rat hemidiaphragm.", "content": "Fenfluramine in therapeutic concentrations causes a significant and dose related increase in glucose uptake into isolated rat and human skeletal muscle in the presence of insulin. Using fenfluramine, 100 ng/ml, on the rat hemidiaphragm preparation the effects of the following receptor blocking drugs in concentrations up to 250 ng/ml were investigated on this phenomenon: atropine, haloperidol, mepyramine, methysergide, propranolol and thymoxamine. Only methysergide, the 5-HT antagonist, reduced the action of fenfluramine in relatively low concentrations of the drug which were dose related (10 ng/ml causing approximately 40% inhibition). This suggests that the peripheral as well as the central actions of fenfluramine are mediated through 5-HT receptors.", "contents": "The effect of methysergide and other receptor antagonists on fenfluramine-induced glucose uptake into the isolated rat hemidiaphragm. Fenfluramine in therapeutic concentrations causes a significant and dose related increase in glucose uptake into isolated rat and human skeletal muscle in the presence of insulin. Using fenfluramine, 100 ng/ml, on the rat hemidiaphragm preparation the effects of the following receptor blocking drugs in concentrations up to 250 ng/ml were investigated on this phenomenon: atropine, haloperidol, mepyramine, methysergide, propranolol and thymoxamine. Only methysergide, the 5-HT antagonist, reduced the action of fenfluramine in relatively low concentrations of the drug which were dose related (10 ng/ml causing approximately 40% inhibition). This suggests that the peripheral as well as the central actions of fenfluramine are mediated through 5-HT receptors."}
{"id": "PMID:192161", "title": "The influence of adenylate cyclase inhibitors on the spontaneous activity of the cardiac pacemaker.", "content": "The effects of adenylate cyclase inhibitors, haloperidol and chlorpromazine, on the spontaneous activity of the rabbit sinus node was studied by means of double sucrose gap and intracellular microelectrodes. Haloperidol and chlorpromazine arrested the spontaneous activity which could be restored with noradrenaline, in the presence of haloperidol, or with dibutyryl c AMP, in the presence of either inhibitor used. After arresting of the spontaneous activity, sinus node cells might utilize metabolic energy supplied from exogenous pyruvate. Pyruvate protected from depolarization or reestablished polarization in depolarized cells but was not able to restore the spontaneous activity. Discussion of these results suggests that c AMP may be directly involved in the spontaneous electrogenesis in the sinus node.", "contents": "The influence of adenylate cyclase inhibitors on the spontaneous activity of the cardiac pacemaker. The effects of adenylate cyclase inhibitors, haloperidol and chlorpromazine, on the spontaneous activity of the rabbit sinus node was studied by means of double sucrose gap and intracellular microelectrodes. Haloperidol and chlorpromazine arrested the spontaneous activity which could be restored with noradrenaline, in the presence of haloperidol, or with dibutyryl c AMP, in the presence of either inhibitor used. After arresting of the spontaneous activity, sinus node cells might utilize metabolic energy supplied from exogenous pyruvate. Pyruvate protected from depolarization or reestablished polarization in depolarized cells but was not able to restore the spontaneous activity. Discussion of these results suggests that c AMP may be directly involved in the spontaneous electrogenesis in the sinus node."}
{"id": "PMID:192157", "title": "Pulmonary fibrosis from amorphous silica dust, a product of silica vapor.", "content": "After prolonged occupation exposure to amorphous silica dust-a product of vaporized crystalline silica (quartz)-eleven out of forty workers showed reticular and/or nodular abnormalities in roentgenograms of the chest. From this group, we present three illustrative cases. These had widespread pulmonary disease with granulomatous nodules and fibrosis (documented histologically in two cases), but there was no demonstrable restrictive impairment of pulmonary function. We discuss the possible importance of this previously underestimated toxicity, especially in an industrial setting.", "contents": "Pulmonary fibrosis from amorphous silica dust, a product of silica vapor. After prolonged occupation exposure to amorphous silica dust-a product of vaporized crystalline silica (quartz)-eleven out of forty workers showed reticular and/or nodular abnormalities in roentgenograms of the chest. From this group, we present three illustrative cases. These had widespread pulmonary disease with granulomatous nodules and fibrosis (documented histologically in two cases), but there was no demonstrable restrictive impairment of pulmonary function. We discuss the possible importance of this previously underestimated toxicity, especially in an industrial setting."}
{"id": "PMID:192162", "title": "Insulin receptor status in disease states of man.", "content": "When insulin or any peptide hormone binds to its receptor on the surface of a target cell, it initiates a series of biochemical steps that ultimately lead to the characteristic action of the hormone. The strength of the signal generated by the hormone depends equally on the hormone concentration, the receptor concentration, and the receptor affinity. Not only do hormone concentrations change rapidly and widely in vivo but so do receptor concentration and affinity. In hormone resistant states, any step in the biochemical pathway of hormone action at the target cell may be involved. Studies of insulin receptors in people indicate that the insulin receptor is altered in many common disorders such as obesity and diabetes, as well as in rare disorders such as extreme insulin resistance due to circulating antibodies directed at the insulin receptor itself. By responding to both intracellular and extracellular events, the insulin receptor is, therefore, a major site for the regulation of target cell responsiveness in vivo.", "contents": "Insulin receptor status in disease states of man. When insulin or any peptide hormone binds to its receptor on the surface of a target cell, it initiates a series of biochemical steps that ultimately lead to the characteristic action of the hormone. The strength of the signal generated by the hormone depends equally on the hormone concentration, the receptor concentration, and the receptor affinity. Not only do hormone concentrations change rapidly and widely in vivo but so do receptor concentration and affinity. In hormone resistant states, any step in the biochemical pathway of hormone action at the target cell may be involved. Studies of insulin receptors in people indicate that the insulin receptor is altered in many common disorders such as obesity and diabetes, as well as in rare disorders such as extreme insulin resistance due to circulating antibodies directed at the insulin receptor itself. By responding to both intracellular and extracellular events, the insulin receptor is, therefore, a major site for the regulation of target cell responsiveness in vivo."}
{"id": "PMID:192163", "title": "[Zollinger-Ellison syndrome and metastatic insulinoma; its response to streptozotocin].", "content": "A patient with pancreatic islet cell carcinoma metastatic to the liver developed Zollinger-Ellison syndrome. She presented hypoglycemic crisis afterwards, which were consequent to insulin excess. After streptozotocin treatment, she remained free of symptoms during the following 12 months.", "contents": "[Zollinger-Ellison syndrome and metastatic insulinoma; its response to streptozotocin]. A patient with pancreatic islet cell carcinoma metastatic to the liver developed Zollinger-Ellison syndrome. She presented hypoglycemic crisis afterwards, which were consequent to insulin excess. After streptozotocin treatment, she remained free of symptoms during the following 12 months."}
{"id": "PMID:192164", "title": "[Post-partum myocardiopathy. Apropos of 25 cases].", "content": "The authors have studied 25 cases of PPC which were selected according to very strict criteria. These cases represent 1 case of PPC for every 2 687 confinements, and 37.8% of all cardiomyopathies in females of child-bearing age. The females with PPC belonged to the more deprived socio-economic population. Multiparity and twin pregnancies are predisposing factors. The clinical picture is usually one of biventricular of left heart failure. Four cases of embolism are included (16%, which is a high figure for Africa). The special investigations are important. Mechanographic studies show a very significant lengthening of the pre-ejection phase (especially QB1), and a reduced ejection phase; haemodynamic studies show in particular increased pressures on the right side in 4 cases out of 6. (3 of which had an arterio-capillary gradient). Angiocardiography, carried out in 4 cases, showed abnormalities especially of the left ventricle (especially dilation and hypokenesia). The outcome may be favourable, especially after 3 to 6 months have elapsed. However, complications may arise in the long-term (10, 14 and 37 months). There were two deaths (8%). Histologically, the lesions were mainly of a congestive type, with some areas of fibrosis, and rarely areas of inflammation (myocarditis). From the aetiological standpoint, it might be thought that during the posptpartum period, various abnormal conditions prevail or would be discovered (13 in our series); but it is also true that some cases of true PPC, with marked stasis and a tendency to thrombosis, as well as severe involvement of the myocardium (as witnessed especially by the mechanographic findings), to progress after 3 months either to resolution, death, or complications; the histological findings in the two fatal cases were of myocarditis.", "contents": "[Post-partum myocardiopathy. Apropos of 25 cases]. The authors have studied 25 cases of PPC which were selected according to very strict criteria. These cases represent 1 case of PPC for every 2 687 confinements, and 37.8% of all cardiomyopathies in females of child-bearing age. The females with PPC belonged to the more deprived socio-economic population. Multiparity and twin pregnancies are predisposing factors. The clinical picture is usually one of biventricular of left heart failure. Four cases of embolism are included (16%, which is a high figure for Africa). The special investigations are important. Mechanographic studies show a very significant lengthening of the pre-ejection phase (especially QB1), and a reduced ejection phase; haemodynamic studies show in particular increased pressures on the right side in 4 cases out of 6. (3 of which had an arterio-capillary gradient). Angiocardiography, carried out in 4 cases, showed abnormalities especially of the left ventricle (especially dilation and hypokenesia). The outcome may be favourable, especially after 3 to 6 months have elapsed. However, complications may arise in the long-term (10, 14 and 37 months). There were two deaths (8%). Histologically, the lesions were mainly of a congestive type, with some areas of fibrosis, and rarely areas of inflammation (myocarditis). From the aetiological standpoint, it might be thought that during the posptpartum period, various abnormal conditions prevail or would be discovered (13 in our series); but it is also true that some cases of true PPC, with marked stasis and a tendency to thrombosis, as well as severe involvement of the myocardium (as witnessed especially by the mechanographic findings), to progress after 3 months either to resolution, death, or complications; the histological findings in the two fatal cases were of myocarditis."}
{"id": "PMID:192165", "title": "Characterization of synchronized cultures of Bumilleriopsis filiformis. Changes in cytochrome-f photooxidation and fluorescence induction kinetics.", "content": "Activity of the photosynthetic apparatus of synchronized cultures was studied with the xanthophycean alga Bumilleriopsis filiformis, following the kinetics of fluorescence induction and photooxidation of cytochrome f (= cytochrome c-553) of intact cells. During the beginning of the cell-division phase, minimum cellular photosynthetic activity is observed and a maximum after its completion, which is accompanied by corresponding changes in Hill reaction activity and re-reduction of cytochrome f by photosystem II light. At minimum activity, the level of steady state fluorescence was higher than at the maximum. This is due, at least in part, to the diminished electron flow between the two photosystems seemingly caused by decreased photosystem I activity. This explanation was suported by the kinetics of cytochrome-f photooxidation. Thus, electron transport activity of both photosystems appears to vary during the cell cycle.", "contents": "Characterization of synchronized cultures of Bumilleriopsis filiformis. Changes in cytochrome-f photooxidation and fluorescence induction kinetics. Activity of the photosynthetic apparatus of synchronized cultures was studied with the xanthophycean alga Bumilleriopsis filiformis, following the kinetics of fluorescence induction and photooxidation of cytochrome f (= cytochrome c-553) of intact cells. During the beginning of the cell-division phase, minimum cellular photosynthetic activity is observed and a maximum after its completion, which is accompanied by corresponding changes in Hill reaction activity and re-reduction of cytochrome f by photosystem II light. At minimum activity, the level of steady state fluorescence was higher than at the maximum. This is due, at least in part, to the diminished electron flow between the two photosystems seemingly caused by decreased photosystem I activity. This explanation was suported by the kinetics of cytochrome-f photooxidation. Thus, electron transport activity of both photosystems appears to vary during the cell cycle."}
{"id": "PMID:192166", "title": "Role of silicon in diatom metabolism. VIII. Cyclic AMP and cyclic GMP in synchronized cultures of Cylindrotheca fusiformis.", "content": "Levels of the cyclic nucleotides, cAMP and cGMP, were determined in four species of pennate diatoms; changes in their levels and ratios were monitored in silicon-starved and light-dark synchronized cultures of Cylindrotheca fusiformis. Content of both cAMP and cGMP changed during the cell cycles: when silicate was added to starved cultures, cAMP, cGMP and DNA levels rose rapidly; cAMP and cGMP declined befor DNA synthesis was complete and continued to fall during the events leading to cell separation. In unstarved synchronies, net synthesis of DNA continued until cell separation; 1 h before cell separation cAMP levels fell while those of cGMP rose. The results support of the proposal that cAMP and cGMP may play a part in the process of cell division in the diatom, possible involving silicon.", "contents": "Role of silicon in diatom metabolism. VIII. Cyclic AMP and cyclic GMP in synchronized cultures of Cylindrotheca fusiformis. Levels of the cyclic nucleotides, cAMP and cGMP, were determined in four species of pennate diatoms; changes in their levels and ratios were monitored in silicon-starved and light-dark synchronized cultures of Cylindrotheca fusiformis. Content of both cAMP and cGMP changed during the cell cycles: when silicate was added to starved cultures, cAMP, cGMP and DNA levels rose rapidly; cAMP and cGMP declined befor DNA synthesis was complete and continued to fall during the events leading to cell separation. In unstarved synchronies, net synthesis of DNA continued until cell separation; 1 h before cell separation cAMP levels fell while those of cGMP rose. The results support of the proposal that cAMP and cGMP may play a part in the process of cell division in the diatom, possible involving silicon."}
{"id": "PMID:192167", "title": "Possible role of cyclic AMP in the synthesis of chlorophyll in Chlorella fusca.", "content": "The intracellular concentration of cAMP in the green alga Chlorella fusca was in the range of 2.10(-9) to 10(-8) moles/g dry weight and was strongly dependent on the growth conditions. The cAMP level was high with high light intensity, low nitrate or glucose concentration. Intracellular cAMP increased only by factor of 2 when high amounts (up to 10(-3) M) of cAMP were added to the medium. Most of the given cAMP was converted to 5'-AMP. Addition of cAMP had little effect on the chlorophyll content of the cells, only at 10(-6) M some enhancement in photoautotrophic cultures was observed. On the other hand high amounts of cAMP in the medium increased the growth rate. DBcAMP* showed a positive effect on chlorophyll synthesis and growth rate at much lower concentrations compared to cAMP. Stimulation effects of exogenous cAMP on the synthesis of chlorophyll were also observed in mixotrophic cultures with a high glucose/nitrate ratio, conditions where chlorophyll synthesis is repressed. Similar to autotrophic conditions DBcAMP was more effective than cAMP. These data indicate that cAMP may act in a system controlling the chlorophyll content of the cells in response to nutrients or light.", "contents": "Possible role of cyclic AMP in the synthesis of chlorophyll in Chlorella fusca. The intracellular concentration of cAMP in the green alga Chlorella fusca was in the range of 2.10(-9) to 10(-8) moles/g dry weight and was strongly dependent on the growth conditions. The cAMP level was high with high light intensity, low nitrate or glucose concentration. Intracellular cAMP increased only by factor of 2 when high amounts (up to 10(-3) M) of cAMP were added to the medium. Most of the given cAMP was converted to 5'-AMP. Addition of cAMP had little effect on the chlorophyll content of the cells, only at 10(-6) M some enhancement in photoautotrophic cultures was observed. On the other hand high amounts of cAMP in the medium increased the growth rate. DBcAMP* showed a positive effect on chlorophyll synthesis and growth rate at much lower concentrations compared to cAMP. Stimulation effects of exogenous cAMP on the synthesis of chlorophyll were also observed in mixotrophic cultures with a high glucose/nitrate ratio, conditions where chlorophyll synthesis is repressed. Similar to autotrophic conditions DBcAMP was more effective than cAMP. These data indicate that cAMP may act in a system controlling the chlorophyll content of the cells in response to nutrients or light."}
{"id": "PMID:192168", "title": "Isolation and characterization of lipid globules from the zoospores of Blastocladiella emersonii.", "content": "Lipid globules were isolated and characterized both chemically and morphologically. They were composed mainly of triglyceride and free sterol, which accounted for over 90% of the total globule content. Smaller amounts of diglyceride, carotenoid, free fatty acid, phospholipid and protein were found. No sterol esters or monoglycerides were detected. Morphologically, the isolated lipid globules resembled the lipid globules in situ. They were spherical, 0.4-1.5 mum in diameter and lacked a trilaminar membrane.", "contents": "Isolation and characterization of lipid globules from the zoospores of Blastocladiella emersonii. Lipid globules were isolated and characterized both chemically and morphologically. They were composed mainly of triglyceride and free sterol, which accounted for over 90% of the total globule content. Smaller amounts of diglyceride, carotenoid, free fatty acid, phospholipid and protein were found. No sterol esters or monoglycerides were detected. Morphologically, the isolated lipid globules resembled the lipid globules in situ. They were spherical, 0.4-1.5 mum in diameter and lacked a trilaminar membrane."}
{"id": "PMID:192169", "title": "Alterations in motor activity, sleep, and biochemistry in a cycling manic-depressive patient.", "content": "Biochemical and electrophysiological factors were studied longitudinally in a rapidly cycling manic-depressive patient. Slow changes in mood, motor activity, sleep, and urinary norepinephrine levels during the course of each depressed and manic episode are reported, as well as rapid alterations in many variables at the time of mood switch. Urinary concentrations of norepinephrine and its metabolite, 3-methoxy-4-hydroxyphenyl glycol (MHPG) were significantly lower in depression than in mania; norepinephrine but not MHPG excretion increased prior to the switch. We postulate that the slow behavioral and biological changes preceding switches in this patient are an important manifestation of the cyclic process in manic-depressive illness.", "contents": "Alterations in motor activity, sleep, and biochemistry in a cycling manic-depressive patient. Biochemical and electrophysiological factors were studied longitudinally in a rapidly cycling manic-depressive patient. Slow changes in mood, motor activity, sleep, and urinary norepinephrine levels during the course of each depressed and manic episode are reported, as well as rapid alterations in many variables at the time of mood switch. Urinary concentrations of norepinephrine and its metabolite, 3-methoxy-4-hydroxyphenyl glycol (MHPG) were significantly lower in depression than in mania; norepinephrine but not MHPG excretion increased prior to the switch. We postulate that the slow behavioral and biological changes preceding switches in this patient are an important manifestation of the cyclic process in manic-depressive illness."}
{"id": "PMID:192170", "title": "Lipoprotein lipase.", "content": "The activity of lipoprotein lipase in the vascular bed represents the major pathway by which triglyceride fatty acid is cleared from the plasma and made available to the epripheral tissues. Recent studies on the properties of the enzyme, both solubilized and membrane-bound have provided new information on the regulation of its activity with the major triglyceride-rich lipoprotein substrates. A key role for this enzyme in the regulation of plasma triglyceride levels is indicated from studies of lipase levels in human adipose tissue and in blood plasma obtained after injection of heparin.", "contents": "Lipoprotein lipase. The activity of lipoprotein lipase in the vascular bed represents the major pathway by which triglyceride fatty acid is cleared from the plasma and made available to the epripheral tissues. Recent studies on the properties of the enzyme, both solubilized and membrane-bound have provided new information on the regulation of its activity with the major triglyceride-rich lipoprotein substrates. A key role for this enzyme in the regulation of plasma triglyceride levels is indicated from studies of lipase levels in human adipose tissue and in blood plasma obtained after injection of heparin."}
{"id": "PMID:192171", "title": "Vasoactive intestinal polypeptide and gastrin-producing islet cell carcinoma.", "content": "A 61-year-old woman had watery diarrhea, hypochlorhydria, hypokalemia, and elevated serum gastrin levels. She had islet cell carcinoma of the body of the pancreas with multiple metastases to the liver. Radioimmunoassay and immunofluorescence demonstrated both vasoactive intestinal polypeptide (VIP) and gastrin in the surgically removed carcinoma and in a metastatic focus. Electron microscopical findings confirmed the presence of two cell types whose secretory granules had characteristics ascribed to these two hormones. Plasma prostaglandin E levels were also elevated above normal. Serum VIP levels became elevated to the Verner-Morrison range prior to her death of a bleeding duodenal ulcer two years after initial symptoms.", "contents": "Vasoactive intestinal polypeptide and gastrin-producing islet cell carcinoma. A 61-year-old woman had watery diarrhea, hypochlorhydria, hypokalemia, and elevated serum gastrin levels. She had islet cell carcinoma of the body of the pancreas with multiple metastases to the liver. Radioimmunoassay and immunofluorescence demonstrated both vasoactive intestinal polypeptide (VIP) and gastrin in the surgically removed carcinoma and in a metastatic focus. Electron microscopical findings confirmed the presence of two cell types whose secretory granules had characteristics ascribed to these two hormones. Plasma prostaglandin E levels were also elevated above normal. Serum VIP levels became elevated to the Verner-Morrison range prior to her death of a bleeding duodenal ulcer two years after initial symptoms."}
{"id": "PMID:192172", "title": "Nerve and muscle in steroid-induced weakness in the rabbit.", "content": "The purpose of this study was (1) to produce a cortisone induced myopathy, (2) to find out whether or not there is an associated neuropathy, and (3) if a cortisone induced neuropathy is produced, to determine its temporal relation to the myopathy. Several corticosteroid preparations were administered to rabbits, in different dosages and for different periods of time in an attempt to produce maximal effects. Decadron and cortisone  acetate in doses of 0.8 mg/kg of body weight and 10 mg/kg of body weight respectively, proved most effective in producing a myopathy. Higher dosages of decadron were fatal, and hydrocortisome, 10 mg/kg of body weight, was not effective. Experimental animals receiving effective doses of decadron, cortisone acetate, and hydrocortisone lost weight, became less agile and, with continued administration of corticosteroids, became immobile. Hind limbs were affected earlier  than forelimbs. The muscle lesion consisted of Z-line irregularity and streaming, vacuolation, variation in fiber size, fragmentation and phagocytosis. Cytologic alterations consisted of Z-line streaming, mitochondrial and lipid aggregates and myofilamentous disarray and disorganization. Sciatic nerve histological and cytological findings were not different from controls. They consisted of minor degrees of thickening and tortuosity of myelin sheaths which occurred in both controls and experimental animals. The electron microscopic findings in the sciatic nerve following cortisone administration have not heretofore been reported in the literature. It is concluded that cortisone myopathy is due to a primary effect of cortisone on skeletal muscle and not secondary to a peripheral nerve lesion.", "contents": "Nerve and muscle in steroid-induced weakness in the rabbit. The purpose of this study was (1) to produce a cortisone induced myopathy, (2) to find out whether or not there is an associated neuropathy, and (3) if a cortisone induced neuropathy is produced, to determine its temporal relation to the myopathy. Several corticosteroid preparations were administered to rabbits, in different dosages and for different periods of time in an attempt to produce maximal effects. Decadron and cortisone  acetate in doses of 0.8 mg/kg of body weight and 10 mg/kg of body weight respectively, proved most effective in producing a myopathy. Higher dosages of decadron were fatal, and hydrocortisome, 10 mg/kg of body weight, was not effective. Experimental animals receiving effective doses of decadron, cortisone acetate, and hydrocortisone lost weight, became less agile and, with continued administration of corticosteroids, became immobile. Hind limbs were affected earlier  than forelimbs. The muscle lesion consisted of Z-line irregularity and streaming, vacuolation, variation in fiber size, fragmentation and phagocytosis. Cytologic alterations consisted of Z-line streaming, mitochondrial and lipid aggregates and myofilamentous disarray and disorganization. Sciatic nerve histological and cytological findings were not different from controls. They consisted of minor degrees of thickening and tortuosity of myelin sheaths which occurred in both controls and experimental animals. The electron microscopic findings in the sciatic nerve following cortisone administration have not heretofore been reported in the literature. It is concluded that cortisone myopathy is due to a primary effect of cortisone on skeletal muscle and not secondary to a peripheral nerve lesion."}
{"id": "PMID:192173", "title": "Sural nerve conduction: a standardized technique.", "content": "Occasionally patients with symptoms and signs suggestive of mild peripheral neuropathy, after routine nerve conduction and electromyographic studies, are found to have values within normal limits. Several authors have suggested that sural nerve conduction studies might be more sensitive indicators of mild peripheral neuropathy. Normal values for sural nerve latencies, amplitudes and conduction velocities have been reported; however, the techniques used have not generally been rigidly standardized. This study describes a standardized and reproducible method of performing human sural nerve conduction studies and presents values obtained from systematically studying a series of 56 normal volunteers.", "contents": "Sural nerve conduction: a standardized technique. Occasionally patients with symptoms and signs suggestive of mild peripheral neuropathy, after routine nerve conduction and electromyographic studies, are found to have values within normal limits. Several authors have suggested that sural nerve conduction studies might be more sensitive indicators of mild peripheral neuropathy. Normal values for sural nerve latencies, amplitudes and conduction velocities have been reported; however, the techniques used have not generally been rigidly standardized. This study describes a standardized and reproducible method of performing human sural nerve conduction studies and presents values obtained from systematically studying a series of 56 normal volunteers."}
{"id": "PMID:192174", "title": "The Harlem regional stroke program: an overview.", "content": "The Harlem regional stroke program has been a demonstration model designed to detect, treat, and follow up stroke and hypertension patients through collaboration with a municipal teaching hospital, community practitioners, local service organizations and a major medical school. Many aspects of the stroke program appear suitable for replication at the local or regional levels in varied settings. In particular, the program has demonstrated the need to link community outreach programs, stressing early detection and preventive-care education, with sustained treatment and follow-up programs. The stroke program has also suggested ways in which specialized programs can be incorporated into long-term comprehensive health planning and care facilities at local and regional levels.", "contents": "The Harlem regional stroke program: an overview. The Harlem regional stroke program has been a demonstration model designed to detect, treat, and follow up stroke and hypertension patients through collaboration with a municipal teaching hospital, community practitioners, local service organizations and a major medical school. Many aspects of the stroke program appear suitable for replication at the local or regional levels in varied settings. In particular, the program has demonstrated the need to link community outreach programs, stressing early detection and preventive-care education, with sustained treatment and follow-up programs. The stroke program has also suggested ways in which specialized programs can be incorporated into long-term comprehensive health planning and care facilities at local and regional levels."}
{"id": "PMID:192175", "title": "Luteinizing hormone and testosterone during nocturnal sleep: relation to penile tumescent cycles.", "content": "Variations of plasma LH and testosterone in relation to sleep-related penile tumescence were assessed. Plasma LH and testosterone were measured at 10-20 min intervals in five normal adult men during 2 nights of sleep. Blood samples were obtained by means of an indwelling venous catheter while sleep was monitored polygraphically and penile tumescence recorded with a penile mercury strain gauge. Tumescent episodes were recorded in all subjects during 9 of the 10 nights of the study, and the percentage of time during sleep, which was associated with tumescence, ranged from 13% to 34%. Simultaneous REM and tumescence comprised 57.7% of total tumescent time. Abrupt elevations of plasma LH and testosterone were observed during the night without a significant relationship to stages of sleep. The mean of all hormonal determinations for the five subjects did not show significant differences in plasma LH and testosterone between fully and partially tumescent episodes and nontumescent periods. Mean testosterone during REM sleep with tumescence, a state of autonomic activation involving sexual function, was consistently higher for the five subjects than during periods free from REM and tumescence.", "contents": "Luteinizing hormone and testosterone during nocturnal sleep: relation to penile tumescent cycles. Variations of plasma LH and testosterone in relation to sleep-related penile tumescence were assessed. Plasma LH and testosterone were measured at 10-20 min intervals in five normal adult men during 2 nights of sleep. Blood samples were obtained by means of an indwelling venous catheter while sleep was monitored polygraphically and penile tumescence recorded with a penile mercury strain gauge. Tumescent episodes were recorded in all subjects during 9 of the 10 nights of the study, and the percentage of time during sleep, which was associated with tumescence, ranged from 13% to 34%. Simultaneous REM and tumescence comprised 57.7% of total tumescent time. Abrupt elevations of plasma LH and testosterone were observed during the night without a significant relationship to stages of sleep. The mean of all hormonal determinations for the five subjects did not show significant differences in plasma LH and testosterone between fully and partially tumescent episodes and nontumescent periods. Mean testosterone during REM sleep with tumescence, a state of autonomic activation involving sexual function, was consistently higher for the five subjects than during periods free from REM and tumescence."}
{"id": "PMID:192176", "title": "Radical pancreatoduodenectomy for cancer of the papilla of Vater.", "content": "Over a 22-year span, 87 patients with carcinoma of the papilla of Vater underwent radical pancreatoduodenectomy. No patient was lost to follow-up, and extended observation was possible in most cases: the definitive operation was at least five years earlier than this study in 87% and at least ten years earlier in 73%. Operative mortality was 11.5% among patients who had a single definitive operative procedure and 15.4% among those whose treatment involved reoperation after prior exploration elsewhere. Overall survival rates at two, five, and ten years were 56%, 34%, and 20% respectively. Factors associated with favorable survival were histologic differentiation (Broders grades 1 and 2), absence of nodal metastasis, and papillary histologic characteristics. Noteworthy is the fact that no patient having resection of an undifferentiated carcinoma (Broders grade 3 or 4) survived four years.", "contents": "Radical pancreatoduodenectomy for cancer of the papilla of Vater. Over a 22-year span, 87 patients with carcinoma of the papilla of Vater underwent radical pancreatoduodenectomy. No patient was lost to follow-up, and extended observation was possible in most cases: the definitive operation was at least five years earlier than this study in 87% and at least ten years earlier in 73%. Operative mortality was 11.5% among patients who had a single definitive operative procedure and 15.4% among those whose treatment involved reoperation after prior exploration elsewhere. Overall survival rates at two, five, and ten years were 56%, 34%, and 20% respectively. Factors associated with favorable survival were histologic differentiation (Broders grades 1 and 2), absence of nodal metastasis, and papillary histologic characteristics. Noteworthy is the fact that no patient having resection of an undifferentiated carcinoma (Broders grade 3 or 4) survived four years."}
{"id": "PMID:192177", "title": "Expression of the human cytomegalovirus genome in mouse cells and in human-mouse heterokaryons.", "content": "Mouse cells with an established human cytomegalovirus (HCMV) infection were fused with susceptible human embryonic fibroblast cells. CMV-specific early antigens could be demonstrated in the cytoplasm and cell-membrane of the heterokaryons. Treatment with 5-iodo-2'-deoxyuridine (IUdR) of the heterokaryons or of the latently infected mouse cells, prior to their fusion with human cells, could induce the appearance of immunoflourescent elements, characterised as late antigens, and of infectious virus. Our data show that the mouse cells, in the latent stage of infection, contain the whole virus genome and that the replication of the virus is controlled by a genetic mechanism of the host cells both in virus-harbouring mouse cells and in heterokaryons.", "contents": "Expression of the human cytomegalovirus genome in mouse cells and in human-mouse heterokaryons. Mouse cells with an established human cytomegalovirus (HCMV) infection were fused with susceptible human embryonic fibroblast cells. CMV-specific early antigens could be demonstrated in the cytoplasm and cell-membrane of the heterokaryons. Treatment with 5-iodo-2'-deoxyuridine (IUdR) of the heterokaryons or of the latently infected mouse cells, prior to their fusion with human cells, could induce the appearance of immunoflourescent elements, characterised as late antigens, and of infectious virus. Our data show that the mouse cells, in the latent stage of infection, contain the whole virus genome and that the replication of the virus is controlled by a genetic mechanism of the host cells both in virus-harbouring mouse cells and in heterokaryons."}
{"id": "PMID:192178", "title": "Altered sensitivity of Rous sarcoma virus transformed cells to inhibition of RNA synthesis by alpha-amanitin.", "content": "Chick embryo cells transformed by Rous sarcoma virus (RSV) continue to synthesize 40--50 percent of control amounts of RNA following 12--24 hour exposure to 2 microng/ml of the toxin whereas normal chick embryo cells similarly treated synthesize less than 5 percent of control amounts of RNA. Analysis of cells treated with alpha-amanitin, or the resistant forms I and III polymerase, do not increase in infected cells over the levels found in uninfected control cells during the first 24 hours following infection indicating that increase in polymerase levels in infected cells does not account for the observed resistance. No significant difference was detected in the sensitivity to alpha-amanitin in the form II polymerase isolated from normal and transformed cells; The greater sensitivity of normal cells to alpha-amanitin can be reduced by growing the cells at low cell density but the resistance of RSV transformed cells is not significantly altered by changes in cell density. The results suggest that the resistance of RSV transformed cells may be related to altered control of density dependent contact-inhibition of the transformed cells.", "contents": "Altered sensitivity of Rous sarcoma virus transformed cells to inhibition of RNA synthesis by alpha-amanitin. Chick embryo cells transformed by Rous sarcoma virus (RSV) continue to synthesize 40--50 percent of control amounts of RNA following 12--24 hour exposure to 2 microng/ml of the toxin whereas normal chick embryo cells similarly treated synthesize less than 5 percent of control amounts of RNA. Analysis of cells treated with alpha-amanitin, or the resistant forms I and III polymerase, do not increase in infected cells over the levels found in uninfected control cells during the first 24 hours following infection indicating that increase in polymerase levels in infected cells does not account for the observed resistance. No significant difference was detected in the sensitivity to alpha-amanitin in the form II polymerase isolated from normal and transformed cells; The greater sensitivity of normal cells to alpha-amanitin can be reduced by growing the cells at low cell density but the resistance of RSV transformed cells is not significantly altered by changes in cell density. The results suggest that the resistance of RSV transformed cells may be related to altered control of density dependent contact-inhibition of the transformed cells."}
{"id": "PMID:192179", "title": "The effect of arginine deprivation on DNA, thymidine kinase and RNA polymerase synthesis in simian virus 40-infected monkey kidney cells.", "content": "In arginine-deprived cells infected with simian virus 40 (SV40), both viral DNA and viral structural proteins were synthesized but infectious virus was not produced. The syntheses of cellular DNA, thymidine kinase and DNA polymerase were induced in virus-infected cells deprived of arginine but the maximum rate of synthesis of these enzymes occurred much later than that in infected cells incubated in the presence of arginine.", "contents": "The effect of arginine deprivation on DNA, thymidine kinase and RNA polymerase synthesis in simian virus 40-infected monkey kidney cells. In arginine-deprived cells infected with simian virus 40 (SV40), both viral DNA and viral structural proteins were synthesized but infectious virus was not produced. The syntheses of cellular DNA, thymidine kinase and DNA polymerase were induced in virus-infected cells deprived of arginine but the maximum rate of synthesis of these enzymes occurred much later than that in infected cells incubated in the presence of arginine."}
{"id": "PMID:192180", "title": "Immunoprecipitation of herpes simplex virus type 1 antigens with different antisera and human cerebrospinal fluids.", "content": "Rabbit convalescent and hyperimmune sera, human patient and blood donor sera, as well as cerebrospinal fluids of humans with herpes simplex virus encephalitis all recognize similar major antigenic components in herpes simplex virus infected rabbit or human cells as shown by electrophoretic analysis of immunoprecipitates. Besides the main glycoproteins with an apparent molecular weight of 100,000 (peak I) the antisera precipitate glycoproteins in a region of an apparent mol. wt. of 60,000--80,000 (peak II), which were resolved into distinct glycoprotein species only by antibody-containing cerebrospinal fluids. The peak II glycoproteins appear on the surface of the infected cell early, and absorb neutralizing antibodies, whereas the peak I glycoproteins are less accessible. Both antigens can be demonstrated in the cell as early as about 2 hours post infection. All major antigenic components studied were found to be glycosylated except one protein with an apparent mol. wt. of 110,000. The herpesvirus specificity of these antigens is demonstrated by a variety of control experiments. The antigens detected are virion components.", "contents": "Immunoprecipitation of herpes simplex virus type 1 antigens with different antisera and human cerebrospinal fluids. Rabbit convalescent and hyperimmune sera, human patient and blood donor sera, as well as cerebrospinal fluids of humans with herpes simplex virus encephalitis all recognize similar major antigenic components in herpes simplex virus infected rabbit or human cells as shown by electrophoretic analysis of immunoprecipitates. Besides the main glycoproteins with an apparent molecular weight of 100,000 (peak I) the antisera precipitate glycoproteins in a region of an apparent mol. wt. of 60,000--80,000 (peak II), which were resolved into distinct glycoprotein species only by antibody-containing cerebrospinal fluids. The peak II glycoproteins appear on the surface of the infected cell early, and absorb neutralizing antibodies, whereas the peak I glycoproteins are less accessible. Both antigens can be demonstrated in the cell as early as about 2 hours post infection. All major antigenic components studied were found to be glycosylated except one protein with an apparent mol. wt. of 110,000. The herpesvirus specificity of these antigens is demonstrated by a variety of control experiments. The antigens detected are virion components."}
{"id": "PMID:192182", "title": "Activation of latent herpesvirus hominis in explants of rabbit trigeminal ganglia: the influence of immune serum.", "content": "More than fifty albino rabbits were inoculated into the right scarified cornea with 10(7) PFU of the Kupka strain of human herpes virus type 1 (HHV-1). At intervals ranging from 4--280 days post infection (p.i.), both gasserian ganglia, both trigeminal nerve trunks and pieces from brain stem and from both corneas were explanted. Activation of the latent HHV-1 was found mainly in the homolateral ganglion tissue, but also in explants originating from the opposite ganglia. Within 24--72 hours, prior to the release of virus into the medium, one infectious unit of HHV was recovered from 10(4)--10(5) cells of the ganglion explant. In addition, a few neurons and satellite cells revealed the presence of virus-specific antigens when the explants were examined by immunofluorescence in serial sections. If the gangia were explanted in the presence of immune serum, the virus recovery rate was at least twice lower as compared to the virus activation in explants kept in the absence of immune serum.", "contents": "Activation of latent herpesvirus hominis in explants of rabbit trigeminal ganglia: the influence of immune serum. More than fifty albino rabbits were inoculated into the right scarified cornea with 10(7) PFU of the Kupka strain of human herpes virus type 1 (HHV-1). At intervals ranging from 4--280 days post infection (p.i.), both gasserian ganglia, both trigeminal nerve trunks and pieces from brain stem and from both corneas were explanted. Activation of the latent HHV-1 was found mainly in the homolateral ganglion tissue, but also in explants originating from the opposite ganglia. Within 24--72 hours, prior to the release of virus into the medium, one infectious unit of HHV was recovered from 10(4)--10(5) cells of the ganglion explant. In addition, a few neurons and satellite cells revealed the presence of virus-specific antigens when the explants were examined by immunofluorescence in serial sections. If the gangia were explanted in the presence of immune serum, the virus recovery rate was at least twice lower as compared to the virus activation in explants kept in the absence of immune serum."}
{"id": "PMID:192183", "title": "In vitro and in vivo inhibition of virus multiplicaton by microwave hyperthemia.", "content": "The effect of microwave hyperthermia (41 degrees and 43 degrees C) on virus multiplication have been explored in vitro (HSV-1 infected primary rabbit kidney cultures) and in vivo (mice infected with HSV-1 or vaccinia). In vitro the cells were inoculated with HSV-1 and heated to 41 degrees or 43 degrees C either before or after infection. Virus yields were significantly decreased when the cells were exposed to hyperthemia within the first few hours after infection, while hyperthemia was without effect when applied before infection or with several hours delay after infection. In mice inoculated intranasally with HSV-1, mortality due to herpes encephalitis was significantly reduced upon daily exposure to microwave hyperthermia from the day of infection onward. In mice inoculated intravenously with vaccinia, a significant decrease in the number of specific tail lesions was observed if the animals were exposed to microwave hyperthermia within the first three days after infection, while irradiation prior to infection or delayed until several days after infection did not exhibit an appreciable effect. Our data suggest that microwave hyperthermia interferes directly with the virus multiplication cycle both in vitro and in vivo.", "contents": "In vitro and in vivo inhibition of virus multiplicaton by microwave hyperthemia. The effect of microwave hyperthermia (41 degrees and 43 degrees C) on virus multiplication have been explored in vitro (HSV-1 infected primary rabbit kidney cultures) and in vivo (mice infected with HSV-1 or vaccinia). In vitro the cells were inoculated with HSV-1 and heated to 41 degrees or 43 degrees C either before or after infection. Virus yields were significantly decreased when the cells were exposed to hyperthemia within the first few hours after infection, while hyperthemia was without effect when applied before infection or with several hours delay after infection. In mice inoculated intranasally with HSV-1, mortality due to herpes encephalitis was significantly reduced upon daily exposure to microwave hyperthermia from the day of infection onward. In mice inoculated intravenously with vaccinia, a significant decrease in the number of specific tail lesions was observed if the animals were exposed to microwave hyperthermia within the first three days after infection, while irradiation prior to infection or delayed until several days after infection did not exhibit an appreciable effect. Our data suggest that microwave hyperthermia interferes directly with the virus multiplication cycle both in vitro and in vivo."}
{"id": "PMID:192184", "title": "Conjunctival impression cytology.", "content": "A new technique is presented using impression of the conjunctiva with a plastic device to study the conjunctival response in various conjunctival disease states. When used with a rapid acting stain the impression technique proved to be accurate, reproducible, and nondestructive when compared to the standard spatula scraping of the conjunctiva using Giemsa stain.", "contents": "Conjunctival impression cytology. A new technique is presented using impression of the conjunctiva with a plastic device to study the conjunctival response in various conjunctival disease states. When used with a rapid acting stain the impression technique proved to be accurate, reproducible, and nondestructive when compared to the standard spatula scraping of the conjunctiva using Giemsa stain."}
{"id": "PMID:192185", "title": "Drug interaction in the eye. Concurrent corticosteroid-antibiotic therapy for inflammatory keratitis.", "content": "Concurrent instillation of individual preparations of a corticosteroid and an antibiotic resulted in significantly (P less than .05) lower peak corneal and aqueous humor steroid levels than those achieved by the steroid alone. Both the interval elapsing between instillation of the two drugs and the sequence in which they were administered influenced subsequent steroid bioavailability. Corticosteroid levels in the cornea after administration of a combination steroid-antibiotic preparation were not significantly different (P less than .05) from those detected after instillation of the same steroid alone, suggesting that, for the treatment of corneal disorders, use of a combination preparation may offer a method to circumvent certain drug interactions. The decrease in ocular steroid bioavailability could not be directly equated with differences in antinflammatory effectiveness, so that the therapeutic relevance of the demonstrated drug interaction is not known.", "contents": "Drug interaction in the eye. Concurrent corticosteroid-antibiotic therapy for inflammatory keratitis. Concurrent instillation of individual preparations of a corticosteroid and an antibiotic resulted in significantly (P less than .05) lower peak corneal and aqueous humor steroid levels than those achieved by the steroid alone. Both the interval elapsing between instillation of the two drugs and the sequence in which they were administered influenced subsequent steroid bioavailability. Corticosteroid levels in the cornea after administration of a combination steroid-antibiotic preparation were not significantly different (P less than .05) from those detected after instillation of the same steroid alone, suggesting that, for the treatment of corneal disorders, use of a combination preparation may offer a method to circumvent certain drug interactions. The decrease in ocular steroid bioavailability could not be directly equated with differences in antinflammatory effectiveness, so that the therapeutic relevance of the demonstrated drug interaction is not known."}
{"id": "PMID:192186", "title": "[Hormone therapy of the juvenile angiofibroma (author's transl)].", "content": "Four juvenile angiofibromas were examined with the electron microscope. Preceding the operation a hormonal therapy with stilbestrol disphosphate (Cytonal, Honvan) was carried out in the cases. The therapeutical effect after application of this drug is clearly correlated to especial changes in histology and cytology. The changes comprise reactions of the vascular component and of the stromal fibroblasts. Endothelial cells and pericytes show a markedly diminished cellular activity, a proliferation of vascular wall cells is not to be proved. The stromal fibroblasts may predominantly be classified as fibroblasts with histiocyte-like features, at which the organelle equipment speaks for a high activity of their metabolism. Furthermore an increased number of myofibroblasts and smooth muscle-like elements are encountered in the stroma. The striking diminution of lesion size and the reduction of disposition to bleeding from the beginning of the hormone therapy is suggested as a direct consequence of cellular contraction. Additionally alterations of synthesis of collagen fibers and ground substance by fibroblasts with histiocyte-like features contribute to a further gradual decrease of the growths.", "contents": "[Hormone therapy of the juvenile angiofibroma (author's transl)]. Four juvenile angiofibromas were examined with the electron microscope. Preceding the operation a hormonal therapy with stilbestrol disphosphate (Cytonal, Honvan) was carried out in the cases. The therapeutical effect after application of this drug is clearly correlated to especial changes in histology and cytology. The changes comprise reactions of the vascular component and of the stromal fibroblasts. Endothelial cells and pericytes show a markedly diminished cellular activity, a proliferation of vascular wall cells is not to be proved. The stromal fibroblasts may predominantly be classified as fibroblasts with histiocyte-like features, at which the organelle equipment speaks for a high activity of their metabolism. Furthermore an increased number of myofibroblasts and smooth muscle-like elements are encountered in the stroma. The striking diminution of lesion size and the reduction of disposition to bleeding from the beginning of the hormone therapy is suggested as a direct consequence of cellular contraction. Additionally alterations of synthesis of collagen fibers and ground substance by fibroblasts with histiocyte-like features contribute to a further gradual decrease of the growths."}
{"id": "PMID:192188", "title": "Adjuvant systemic therapy in \"early\" breast cancer.", "content": "\"Early\" breast cancer is a systemic disease in the majority of cases. Progress has been and is being made toward the determination of those women at risk of recurrence. Attractive as it seems, the value of systemic adjuvant therapy, given at the time of minimal tumour load i.e., after mastectomy, is not proven. Therefore, for the average case it is better to treat the cancer locally and to observe and leave further evaluation of systemic therapy to those centres which are able to conduct controlled, randomized trails.", "contents": "Adjuvant systemic therapy in \"early\" breast cancer. \"Early\" breast cancer is a systemic disease in the majority of cases. Progress has been and is being made toward the determination of those women at risk of recurrence. Attractive as it seems, the value of systemic adjuvant therapy, given at the time of minimal tumour load i.e., after mastectomy, is not proven. Therefore, for the average case it is better to treat the cancer locally and to observe and leave further evaluation of systemic therapy to those centres which are able to conduct controlled, randomized trails."}
{"id": "PMID:192190", "title": "Fine structure of a virilizing adrenocortical adenoma.", "content": "An adrenocortical adenoma associated with adrenogenital syndrome in a two-year-old boy was investigated light and electron microscopically. Urinary 17-ketosteroid excretion was considerably elevated and unresponsive to dexamethasone administration. The level returned to normal after surgical removal of the tumour. Adenomatous cells display striking cellular and nuclear pleomorphism. Megalocytes with huge nuclei and nucleoli frequently occur. Deep cytoplasmic indentations cause nuclear pseudoinclusions and bizarre shape of the nuclei. True nuclear inclusions are also seen, as well as nuclear fragmentation. Cytoplasmic organelles show striking morphological alterations. Mitochondria with lamellar and tubular cristae are transformed into round or ovoid organelles of vesicular type. Their internal compartment is reduced, matrix material increases relatively, and mitochondrial inclusion bodies develop. Mitochondrial inclusions are identified as corresponding to fuchsinophil (siderophil or argyrophil) granules seen in the light microscope. Their staining properties indicate their glycoprotein nature. Vesicular profiles of smooth endoplasmic reticulum predominate and stacks of rough endoplasmic reticulum are transformed into tubules and vesicles. In Golgi regions, only vesicular elements are enriched. Lipid droplets are scarce. It was not possible to demonstrate histochemically catalase activity in microbodies. Dense bodies only occur in small, undifferentiated tumour cells. Multivesicular bodies, autophagosomes and residual bodies are rare. Lipofuscin is absent. Tumour cells are thought to derive from a population of undifferentiated cells (\"germinative tumour cells\"). Their morphological features and organelle equipment during a hypothetical course of differentiation and following dedifferentiation is described and discussed with respect to exceeding androgen synthesis.", "contents": "Fine structure of a virilizing adrenocortical adenoma. An adrenocortical adenoma associated with adrenogenital syndrome in a two-year-old boy was investigated light and electron microscopically. Urinary 17-ketosteroid excretion was considerably elevated and unresponsive to dexamethasone administration. The level returned to normal after surgical removal of the tumour. Adenomatous cells display striking cellular and nuclear pleomorphism. Megalocytes with huge nuclei and nucleoli frequently occur. Deep cytoplasmic indentations cause nuclear pseudoinclusions and bizarre shape of the nuclei. True nuclear inclusions are also seen, as well as nuclear fragmentation. Cytoplasmic organelles show striking morphological alterations. Mitochondria with lamellar and tubular cristae are transformed into round or ovoid organelles of vesicular type. Their internal compartment is reduced, matrix material increases relatively, and mitochondrial inclusion bodies develop. Mitochondrial inclusions are identified as corresponding to fuchsinophil (siderophil or argyrophil) granules seen in the light microscope. Their staining properties indicate their glycoprotein nature. Vesicular profiles of smooth endoplasmic reticulum predominate and stacks of rough endoplasmic reticulum are transformed into tubules and vesicles. In Golgi regions, only vesicular elements are enriched. Lipid droplets are scarce. It was not possible to demonstrate histochemically catalase activity in microbodies. Dense bodies only occur in small, undifferentiated tumour cells. Multivesicular bodies, autophagosomes and residual bodies are rare. Lipofuscin is absent. Tumour cells are thought to derive from a population of undifferentiated cells (\"germinative tumour cells\"). Their morphological features and organelle equipment during a hypothetical course of differentiation and following dedifferentiation is described and discussed with respect to exceeding androgen synthesis."}
{"id": "PMID:192191", "title": "Pyrimidine biosynthesis in Serratia marcescens: a possible role for nonsequential enzyme interactions in mimicking coordinate gene expression.", "content": "The coordinate expression of four sequential enzymes in the de novo pyrimidine pathway may result from the interaction of the various polypeptides of the pathway in Serratia marcescens rather than represent some unit of transcriptional regulation. These interactions were defined by examining the polypeptide association observed in extracts of parental and mutant strains in a series of pleiotropic pyrimidine auxotrophs. Extracts of pyrE auxotrophs [processing dihydroorotate (DHOase) activity but no orotidine-5'-monophosphate pyrophosphorylase (OMPppase) activity] stimulate OMPppase activity in extracts of pyrC auxotrophs (posessing reduced OMPppase activity but no DHOase activity). Separation by molecular weight on Sephadex G200 has suggested an aggregation between the final two enzymes, OMPppase and OMPdecarboxylase (OMPdecase), and the earlier enzyme, DHOase. The reduction of OMPppase activity in pyrC auxotrophs (encoding either a defective polypeptide or reduced levels) is explained by the lack of adequate levels of DHOase for aggregate formation. Such polypeptide interactions appear to mimic the coordinate formation of polypeptides which are controlled as a unit of regulation. The measurable levels of enzymatic activity vary in a quantitatively identical manner, but the variation does not result directly from the regulation of polypeptide formation.", "contents": "Pyrimidine biosynthesis in Serratia marcescens: a possible role for nonsequential enzyme interactions in mimicking coordinate gene expression. The coordinate expression of four sequential enzymes in the de novo pyrimidine pathway may result from the interaction of the various polypeptides of the pathway in Serratia marcescens rather than represent some unit of transcriptional regulation. These interactions were defined by examining the polypeptide association observed in extracts of parental and mutant strains in a series of pleiotropic pyrimidine auxotrophs. Extracts of pyrE auxotrophs [processing dihydroorotate (DHOase) activity but no orotidine-5'-monophosphate pyrophosphorylase (OMPppase) activity] stimulate OMPppase activity in extracts of pyrC auxotrophs (posessing reduced OMPppase activity but no DHOase activity). Separation by molecular weight on Sephadex G200 has suggested an aggregation between the final two enzymes, OMPppase and OMPdecarboxylase (OMPdecase), and the earlier enzyme, DHOase. The reduction of OMPppase activity in pyrC auxotrophs (encoding either a defective polypeptide or reduced levels) is explained by the lack of adequate levels of DHOase for aggregate formation. Such polypeptide interactions appear to mimic the coordinate formation of polypeptides which are controlled as a unit of regulation. The measurable levels of enzymatic activity vary in a quantitatively identical manner, but the variation does not result directly from the regulation of polypeptide formation."}
{"id": "PMID:192192", "title": "The action of progesterone and diethylstilboestrol on the dehydrogenase and esterase activities of a purified aldehyde dehydrogenase from rabbit liver.", "content": "A steroid-sensitive aldehyde dehydrogenase (EC 1.2.1.3) was purified from rabbit liver and is homogeneous by the criterion of electrophoresis in polyacrylamide gels with or without sodium dodecyl sulphate. The enzyme is tetrameric, of subunit mo.wt. 48 300, and contains no tightly bound zinc. The fluorescence of the protein is decreased in the presence of progesterone, which is inhibitory to the reactions catalysed by the enzyme. When NADH is bound to the enzyme, the fluorescence of the coenzyme is augmented to an extent independent of the presence of steroids or acetaldehyde. The purified enzyme catalyses the oxidation of acetaldehyde and glucuronolactone, and the hydrolysis of 4-nitrophenyl acetate. Each of these reactions is inhibited by progesterone in such a manner as to suggest the formation of a catalytically active enzyme-hormone complex. Diethylstilboestrol inhibits the hydrolysis of esters by this enzyme, but stimulates the oxidation of aldehydes, except at low aldehyde concentrations; the ligand is then inhibitory. NADH inhibits the hydrolysis of 4-nitrophenyl acetate by the enzyme in a partially competitive fashion.", "contents": "The action of progesterone and diethylstilboestrol on the dehydrogenase and esterase activities of a purified aldehyde dehydrogenase from rabbit liver. A steroid-sensitive aldehyde dehydrogenase (EC 1.2.1.3) was purified from rabbit liver and is homogeneous by the criterion of electrophoresis in polyacrylamide gels with or without sodium dodecyl sulphate. The enzyme is tetrameric, of subunit mo.wt. 48 300, and contains no tightly bound zinc. The fluorescence of the protein is decreased in the presence of progesterone, which is inhibitory to the reactions catalysed by the enzyme. When NADH is bound to the enzyme, the fluorescence of the coenzyme is augmented to an extent independent of the presence of steroids or acetaldehyde. The purified enzyme catalyses the oxidation of acetaldehyde and glucuronolactone, and the hydrolysis of 4-nitrophenyl acetate. Each of these reactions is inhibited by progesterone in such a manner as to suggest the formation of a catalytically active enzyme-hormone complex. Diethylstilboestrol inhibits the hydrolysis of esters by this enzyme, but stimulates the oxidation of aldehydes, except at low aldehyde concentrations; the ligand is then inhibitory. NADH inhibits the hydrolysis of 4-nitrophenyl acetate by the enzyme in a partially competitive fashion."}
{"id": "PMID:192193", "title": "A functioning complex between tryptic fragments of cytochrome c. A route to the production of semisynthetic analogues.", "content": "We report the discovery of a functioning non-covalent complex between two peptides obtained from a limited tryptic digest of horse heart cytochrome c. We have used the phenomenon to produce three modified versions of the complex. We have replaced lysine-39 semisynthetically with ornithine in the first analogue, with p-fluorophenyl-alanine in the second, and removed it  entirely in the third.", "contents": "A functioning complex between tryptic fragments of cytochrome c. A route to the production of semisynthetic analogues. We report the discovery of a functioning non-covalent complex between two peptides obtained from a limited tryptic digest of horse heart cytochrome c. We have used the phenomenon to produce three modified versions of the complex. We have replaced lysine-39 semisynthetically with ornithine in the first analogue, with p-fluorophenyl-alanine in the second, and removed it  entirely in the third."}
{"id": "PMID:192194", "title": "Purification of glycolytic enzymes by using affinity-elution chromatography.", "content": "1. A systematic procedure for the purification of enzymes by affinity-elution chromatography is described. Enzymes are adsorbed on a cation-exchanger, and eluted with ligands specific for the enzyme concerned. 2. All of the glycolytic and some related enzymes present in rabbit muscle can be purified by the affinity-elution technique. The pH range for adsorption and elution of each enzyme was found, and the effects of minor variations of conditions are described. 3. A description of experimental conditions suitable for affinity elution of each enzyme is given, together with special features relevant to each individual enzyme. 4. Theoretical considerations of affinity elution chromatography are discussed, including its limitations, advantages and disadvantages compared with affinity-adsorption chromatography. Possible developments are suggested to cover enzymes which because of their adsorption characteristics are not at present amenable to affinity-elution procedures.", "contents": "Purification of glycolytic enzymes by using affinity-elution chromatography. 1. A systematic procedure for the purification of enzymes by affinity-elution chromatography is described. Enzymes are adsorbed on a cation-exchanger, and eluted with ligands specific for the enzyme concerned. 2. All of the glycolytic and some related enzymes present in rabbit muscle can be purified by the affinity-elution technique. The pH range for adsorption and elution of each enzyme was found, and the effects of minor variations of conditions are described. 3. A description of experimental conditions suitable for affinity elution of each enzyme is given, together with special features relevant to each individual enzyme. 4. Theoretical considerations of affinity elution chromatography are discussed, including its limitations, advantages and disadvantages compared with affinity-adsorption chromatography. Possible developments are suggested to cover enzymes which because of their adsorption characteristics are not at present amenable to affinity-elution procedures."}
{"id": "PMID:192195", "title": "The disulphide-bonded nature of procollagen and the role of the extension peptides in the assembly of the molecule.", "content": "1. The molecular weights of chick tendon and cartilage procollagens, and their constituent polypeptides, were determined by gel filtration and gel electrophoresis. The values obtained are in good agreement and indicate that the mol.wts. of the secreted procollagens (types I and II) and their individual pro-alpha-chains are of the order of 405 000-445 000 and 137 000-145 000 respectively.2. Digestion of tendon procollagen with human rheumatoid synovial collagenase gave products consistent with the presence of large non-helical peptide extensions at both N-and C-termini. Electrophoretic analysis gave apparent mol.wts. of 17 500 and 36 000 for the respective N- and C-terminal extensions of pro-alpha1(I)-and pro-alpha2-chains, and inter-chain disulphide bonds were restricted to the C-terminal location. 3. During the biosynthesis of procollagen by tendon and cartilage cells a close correlation was observed between the extent of inter-chain disulphide bonding and the proportion of procollagen polypeptides having a triple-helical conformation. These processes appeared to commence in the rough endoplasmic reticulum and be completed in the smooth endoplasmic reticulum, but the rate at which they occur in cartilage cells is markedly slower than that found in tendon cells. 4. When the intracellular [14C]procollagen polypeptides present in the rough-endoplasmic-reticulum fractions of tendon and cartilage cells were analysed under non-reducing conditions on agarose/polyacrylamide composite gels, no significant pools of dimeric intermediates were detected. 5. In both cell types, inter-chain disulphide-bond formation occurred even when hydroxylation, and hence triple-helix formation, was inhibited. The presence of pro-alpha1- and pro-alpha2-components in a ratio of 2:1 in the disulphide-linked unhydroxylated procollagen isolated from tendon cells demonstrated that correct chain association occurs in the absence of hydroxylation. This observation is consistent with a model for the assembly of pro-gamma112-chains in which the recognition and selection of pro-alpha1-and pro-alpha2-chains in a 2:1 ratio are directed by the non-helical C-terminal extension peptides of tendon procollagen.", "contents": "The disulphide-bonded nature of procollagen and the role of the extension peptides in the assembly of the molecule. 1. The molecular weights of chick tendon and cartilage procollagens, and their constituent polypeptides, were determined by gel filtration and gel electrophoresis. The values obtained are in good agreement and indicate that the mol.wts. of the secreted procollagens (types I and II) and their individual pro-alpha-chains are of the order of 405 000-445 000 and 137 000-145 000 respectively.2. Digestion of tendon procollagen with human rheumatoid synovial collagenase gave products consistent with the presence of large non-helical peptide extensions at both N-and C-termini. Electrophoretic analysis gave apparent mol.wts. of 17 500 and 36 000 for the respective N- and C-terminal extensions of pro-alpha1(I)-and pro-alpha2-chains, and inter-chain disulphide bonds were restricted to the C-terminal location. 3. During the biosynthesis of procollagen by tendon and cartilage cells a close correlation was observed between the extent of inter-chain disulphide bonding and the proportion of procollagen polypeptides having a triple-helical conformation. These processes appeared to commence in the rough endoplasmic reticulum and be completed in the smooth endoplasmic reticulum, but the rate at which they occur in cartilage cells is markedly slower than that found in tendon cells. 4. When the intracellular [14C]procollagen polypeptides present in the rough-endoplasmic-reticulum fractions of tendon and cartilage cells were analysed under non-reducing conditions on agarose/polyacrylamide composite gels, no significant pools of dimeric intermediates were detected. 5. In both cell types, inter-chain disulphide-bond formation occurred even when hydroxylation, and hence triple-helix formation, was inhibited. The presence of pro-alpha1- and pro-alpha2-components in a ratio of 2:1 in the disulphide-linked unhydroxylated procollagen isolated from tendon cells demonstrated that correct chain association occurs in the absence of hydroxylation. This observation is consistent with a model for the assembly of pro-gamma112-chains in which the recognition and selection of pro-alpha1-and pro-alpha2-chains in a 2:1 ratio are directed by the non-helical C-terminal extension peptides of tendon procollagen."}
{"id": "PMID:192196", "title": "Preparation and properties of nylon-tube-supported nicotinamide--adenine dinucleotide kinase.", "content": "Pigeon liver NAD kinase was covalently coupled to the inside surfaces of nylon tubes, both directly to the nylon and via polyamine specers Km values and the inactivation energy of the reaction changed upon immobilization, but the pH-dependence remained unaltered. The activities and stabilities of different preparations are compared.", "contents": "Preparation and properties of nylon-tube-supported nicotinamide--adenine dinucleotide kinase. Pigeon liver NAD kinase was covalently coupled to the inside surfaces of nylon tubes, both directly to the nylon and via polyamine specers Km values and the inactivation energy of the reaction changed upon immobilization, but the pH-dependence remained unaltered. The activities and stabilities of different preparations are compared."}
{"id": "PMID:192197", "title": "Studies in vitro of the effects of adenosine 3':5'-cyclic monophosphate on the phosphorylation of nuclear proteins in isolated rat heart nuclei.", "content": "Isolated rat heart nuclei were prepared by homogenization and sucrose-density-gradient centrifugation. The protein/DNA ratio of these nuclei was 3.1:1 (w/w), and the histones/non-histone proteins/DNA proportions were 1.4:1.6:1 (by wt.). Non-histone proteins were fractionated into six major groups by elution on a quaternized anion-exchanger (QAE-Sephadex A-50 column with increasing concentrations of NaCl in 5M-urea/0.01 M-Tris/HCl buffer (pH8.3). When isolated nuclei were incubated in a medium containing [gamma-32P]ATP, a differential distribution of 32P was observed in the six fractions of nonhistone proteins. The fractions eluted from the Sephadex column with 0.35M- and 0.6M-NaCl contained contained 80% of the total radioactivity incorporated into the non-histone proteins. This incorporation into the 0.35M- and 0.6M-NaCl fractions was increased by 66 and 112% respectively in the presence of cyclic AMP. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of these two particular fractions showed a selective increase in labelling of five protein bands in the presence of cyclic AMP.", "contents": "Studies in vitro of the effects of adenosine 3':5'-cyclic monophosphate on the phosphorylation of nuclear proteins in isolated rat heart nuclei. Isolated rat heart nuclei were prepared by homogenization and sucrose-density-gradient centrifugation. The protein/DNA ratio of these nuclei was 3.1:1 (w/w), and the histones/non-histone proteins/DNA proportions were 1.4:1.6:1 (by wt.). Non-histone proteins were fractionated into six major groups by elution on a quaternized anion-exchanger (QAE-Sephadex A-50 column with increasing concentrations of NaCl in 5M-urea/0.01 M-Tris/HCl buffer (pH8.3). When isolated nuclei were incubated in a medium containing [gamma-32P]ATP, a differential distribution of 32P was observed in the six fractions of nonhistone proteins. The fractions eluted from the Sephadex column with 0.35M- and 0.6M-NaCl contained contained 80% of the total radioactivity incorporated into the non-histone proteins. This incorporation into the 0.35M- and 0.6M-NaCl fractions was increased by 66 and 112% respectively in the presence of cyclic AMP. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of these two particular fractions showed a selective increase in labelling of five protein bands in the presence of cyclic AMP."}
{"id": "PMID:192198", "title": "Human collagen 'fingerprints' produced by clostridopeptidase A digestion and high-pressure liquid chromatography.", "content": "Samples (1-2mg) of purified human type I, II and III collagens and alpha1(I) and alpha2 chains were digested with clostridiopeptidase A and the released peptides analysed by ion-exchange high-pressure liquid chromatography. Specific 'fingerprints' were produced for each type of collagen. The reproducible nature of these 'fingerprints' and the reconstitution of the type I 'fingerprint' from the 'fingerprints' of the component alpha1(I) and alpha2 chains showed that the specificity of these 'fingerprints' was related to the primary structure of each type of collagen. In addition, some of the differences observed between the 'fingerprints' of the alpha1(I) and alpha2 chains of type I collagen were shown to be suitable for the quantitative analysis of these chains.", "contents": "Human collagen 'fingerprints' produced by clostridopeptidase A digestion and high-pressure liquid chromatography. Samples (1-2mg) of purified human type I, II and III collagens and alpha1(I) and alpha2 chains were digested with clostridiopeptidase A and the released peptides analysed by ion-exchange high-pressure liquid chromatography. Specific 'fingerprints' were produced for each type of collagen. The reproducible nature of these 'fingerprints' and the reconstitution of the type I 'fingerprint' from the 'fingerprints' of the component alpha1(I) and alpha2 chains showed that the specificity of these 'fingerprints' was related to the primary structure of each type of collagen. In addition, some of the differences observed between the 'fingerprints' of the alpha1(I) and alpha2 chains of type I collagen were shown to be suitable for the quantitative analysis of these chains."}
{"id": "PMID:192199", "title": "A latent form of collagenase in the involuting rat uterus and its activation by a serine proteinase.", "content": "1. The involuting rat uterus displays an extremely rapid breakdown of collagen. Collagenase activity can be assayed directly in the insoluble 6000g pellet of uterine homogenates. At 1 day post partum, about 85% of this collagenase activity is in a latent form. 2. This latent form can be activated by trypsin or by a serine proteinase present in the uterine pellets. 3. The activating enzyme of the tissue is inhibited by a wide spectrum of trypsin inhibitors, including Trasylol, soya-bean and lima-bean trypsin inhibitors, snail inhibitor and di-isopropyl phosphoro-fluoridate. Partial inhibition is produced by benzamidine, phenylmethanesulphonyl fluoride, epsilon-aminohexanoate, leupeptin, antipain and alpha1-antitrypsin. Ovomucoid, 7-amino-1-chloro-3-tosylamido-1-heptan-2-one and 1-chloro-4-phenyl-3-(N-benzyloxy-carbonyl)amino-L-butan-2-one are not inhibitory. 4. Extraction of uterine pellets with 0.1 M-CaCl2 at 60 degrees C releases both latent and active collagenase. Exclusion chromatography on Sephadex G-100 gives an apparent molecular weight of approx. 77000 for the latent form and 66000 for the active form. The latent form is suggested to be a zymogen of collagenase.", "contents": "A latent form of collagenase in the involuting rat uterus and its activation by a serine proteinase. 1. The involuting rat uterus displays an extremely rapid breakdown of collagen. Collagenase activity can be assayed directly in the insoluble 6000g pellet of uterine homogenates. At 1 day post partum, about 85% of this collagenase activity is in a latent form. 2. This latent form can be activated by trypsin or by a serine proteinase present in the uterine pellets. 3. The activating enzyme of the tissue is inhibited by a wide spectrum of trypsin inhibitors, including Trasylol, soya-bean and lima-bean trypsin inhibitors, snail inhibitor and di-isopropyl phosphoro-fluoridate. Partial inhibition is produced by benzamidine, phenylmethanesulphonyl fluoride, epsilon-aminohexanoate, leupeptin, antipain and alpha1-antitrypsin. Ovomucoid, 7-amino-1-chloro-3-tosylamido-1-heptan-2-one and 1-chloro-4-phenyl-3-(N-benzyloxy-carbonyl)amino-L-butan-2-one are not inhibitory. 4. Extraction of uterine pellets with 0.1 M-CaCl2 at 60 degrees C releases both latent and active collagenase. Exclusion chromatography on Sephadex G-100 gives an apparent molecular weight of approx. 77000 for the latent form and 66000 for the active form. The latent form is suggested to be a zymogen of collagenase."}
{"id": "PMID:192200", "title": "Studies on the mechanism and kinetics of the 2-oxoglutarate dehydrogenase system from pig heart.", "content": "1. The kinetic properties of the 2-oxoglutarate dehydrogenase system were investigated. To this end, initial-velocity studies were carried out by the method of Fromm [(1967) Biochim. Biophys. Acta 139, 221-230]. Reciprocal plots of the results did not agree with those expected for the Hexa Uni Ping Pong mechanism previously proposed for the system. 2. The measured initial velocities were fitted to initial-rate equations corresponding to several possible mechanisms by using a computer optimization technique. Statistical analyses performed on the results of the optimization studies indicated that one mechanism was a significantly better fit to the experimental data than the other mechanisms tested. This mechanism is one in which there is a random order of binding of NAD+ and CoA and release of succinyl-CoA, although the binding of 2-oxoglutarate and release of CO2 is still given a Ping Pong mechanism, which precedes the binding of the other substrates. These conclusions were supported by NADH-inhibition studies. 3. The usefulness of the method of fitting initial-rate data to rate equations and the applicability of the proposed enzymic mechanism to the enzyme complex are discussed.", "contents": "Studies on the mechanism and kinetics of the 2-oxoglutarate dehydrogenase system from pig heart. 1. The kinetic properties of the 2-oxoglutarate dehydrogenase system were investigated. To this end, initial-velocity studies were carried out by the method of Fromm [(1967) Biochim. Biophys. Acta 139, 221-230]. Reciprocal plots of the results did not agree with those expected for the Hexa Uni Ping Pong mechanism previously proposed for the system. 2. The measured initial velocities were fitted to initial-rate equations corresponding to several possible mechanisms by using a computer optimization technique. Statistical analyses performed on the results of the optimization studies indicated that one mechanism was a significantly better fit to the experimental data than the other mechanisms tested. This mechanism is one in which there is a random order of binding of NAD+ and CoA and release of succinyl-CoA, although the binding of 2-oxoglutarate and release of CO2 is still given a Ping Pong mechanism, which precedes the binding of the other substrates. These conclusions were supported by NADH-inhibition studies. 3. The usefulness of the method of fitting initial-rate data to rate equations and the applicability of the proposed enzymic mechanism to the enzyme complex are discussed."}
{"id": "PMID:192201", "title": "Adenosine diphosphate ribosylated histones.", "content": "When rat liver nuclei were incubated with [adenine-3H]NAD, besides histone 1, histone 2A and especially histone 2B accepted 3H radioactivity. 3H radioactivity was also found on the non-histone proteins and on the small amounts of histones 1 and 3 released into the supernatant during incubation. [14C]Adenine uptake in vivo by liver and thymus nuclei showed radioactivity in histones 1 and 3. After digestion with Pronase and leucine aminopeptidase 14C- or 32P-labelled histone 3 released a serine phosphate-containing nucleotide, which on acid hydrolysis yielded ADP-ribose and serine phosphate. Serine phosphate was also found in the material from the nucleotide peaks from histones 2A and 2B. ADP-ribosylated histones 1 and 3 were more easily released from nuclei than their unmodified forms and showed higher [32P]Pi and [3H]lysine uptakes in vivo [Ord & Stocken (1975) FEBS Meet. Proc. 34, 113-125].", "contents": "Adenosine diphosphate ribosylated histones. When rat liver nuclei were incubated with [adenine-3H]NAD, besides histone 1, histone 2A and especially histone 2B accepted 3H radioactivity. 3H radioactivity was also found on the non-histone proteins and on the small amounts of histones 1 and 3 released into the supernatant during incubation. [14C]Adenine uptake in vivo by liver and thymus nuclei showed radioactivity in histones 1 and 3. After digestion with Pronase and leucine aminopeptidase 14C- or 32P-labelled histone 3 released a serine phosphate-containing nucleotide, which on acid hydrolysis yielded ADP-ribose and serine phosphate. Serine phosphate was also found in the material from the nucleotide peaks from histones 2A and 2B. ADP-ribosylated histones 1 and 3 were more easily released from nuclei than their unmodified forms and showed higher [32P]Pi and [3H]lysine uptakes in vivo [Ord & Stocken (1975) FEBS Meet. Proc. 34, 113-125]."}
{"id": "PMID:192202", "title": "Cholera toxin requires oxidized nicotinamide-adenine dinucleotide to activate adenylate cyclase in purified rat liver plasma membranes.", "content": "Activation of adenylate cyclase in isolated rat liver plasma membranes by cholera toxin was demonstrated. The activation requires the presence of NAD+ and ATP and is irreversible.", "contents": "Cholera toxin requires oxidized nicotinamide-adenine dinucleotide to activate adenylate cyclase in purified rat liver plasma membranes. Activation of adenylate cyclase in isolated rat liver plasma membranes by cholera toxin was demonstrated. The activation requires the presence of NAD+ and ATP and is irreversible."}
{"id": "PMID:192203", "title": "Factors affecting the binding of [3H]adenosine 3':5'-cyclic monophosphate to protein kinase from bovine adrenal cortex.", "content": "Inorganic salts, several proteins and traces of protein precipitants were tested to find out by what mechanisms they modulate the binding of cyclic [3H]AMP to protein kinase (ATP-protein phosphotransferase; EC 2.7.1.37). The separation of free and bound cyclic AMP by (NH4)2SO4 precipitation was unaffected by the above agents and was more reliable than the Millipore filtration technique. Several binding sites for cyclic AMP were revealed in adrenal-cortex extract. When this extract was used as binding reagent in an assay for cyclic AMP, the standard curve was distorted in the presence of KCl because the salt affected the different binding sites to a varying extent. At high ionic strenth the protein kinase isoenzyme I dissociated and showed an extraordinarily high affinity for cyclic AMP. Trichloroacetate and perchlorate at very low concentrations were able to dissociate the protein kinase and modulate its binding characteristics as well. A progressive decrease in the cyclic AMP-binding capacity occurred on prolonged incubations. The binding protein was protected against inactivation by 2-mercaptoethanol, EDTA and several proteins. It was more resistant to denaturation when complexed to cyclic AMP. The enhancement of cyclic AMP binding by bovine serum albumin was investigated in some detail and appeared to be a pure stabilizing effect. It is proposed that the competitive-binding assays for cyclic AMP based on protein kinase be conducted at high ionic strength and in the presence of stabilizers (protein, EDTA, 2-mercaptoethanol). The interference from agents that may dissociate the protein kinase or influence its stability will thus be decreased.", "contents": "Factors affecting the binding of [3H]adenosine 3':5'-cyclic monophosphate to protein kinase from bovine adrenal cortex. Inorganic salts, several proteins and traces of protein precipitants were tested to find out by what mechanisms they modulate the binding of cyclic [3H]AMP to protein kinase (ATP-protein phosphotransferase; EC 2.7.1.37). The separation of free and bound cyclic AMP by (NH4)2SO4 precipitation was unaffected by the above agents and was more reliable than the Millipore filtration technique. Several binding sites for cyclic AMP were revealed in adrenal-cortex extract. When this extract was used as binding reagent in an assay for cyclic AMP, the standard curve was distorted in the presence of KCl because the salt affected the different binding sites to a varying extent. At high ionic strenth the protein kinase isoenzyme I dissociated and showed an extraordinarily high affinity for cyclic AMP. Trichloroacetate and perchlorate at very low concentrations were able to dissociate the protein kinase and modulate its binding characteristics as well. A progressive decrease in the cyclic AMP-binding capacity occurred on prolonged incubations. The binding protein was protected against inactivation by 2-mercaptoethanol, EDTA and several proteins. It was more resistant to denaturation when complexed to cyclic AMP. The enhancement of cyclic AMP binding by bovine serum albumin was investigated in some detail and appeared to be a pure stabilizing effect. It is proposed that the competitive-binding assays for cyclic AMP based on protein kinase be conducted at high ionic strength and in the presence of stabilizers (protein, EDTA, 2-mercaptoethanol). The interference from agents that may dissociate the protein kinase or influence its stability will thus be decreased."}
{"id": "PMID:192204", "title": "Effects of prostaglandin on substrate uptake and cell division in human diploid fibroblasts.", "content": "PG (prostaglandin) E1 inhibits the uptake of iridine, thymidine, 2-deoxy-D-glucose and L-isoleucine into human diploid WI38 fibroblasts. The inhibition occurs within seconds of the addition of the prostaglandin to the culture. PGE2, PGF1alpha and PGF2alpha behave similarly. Arachidonic acid and 8,11,14-eicosatrienoic acid also decrease uptake in the presence or absence of indomethacin. Other unsaturated fatty acids such as oleic acid, linoleic acid and linolenic acid are essentially inactive. Ricinoleic acid (the 9-hydroxyoleic acid), however, inhibits uptake to about the same degree, at concentrations similar to those of the prostaglandins. Results indicate that this rapid blockage by the prostaglandins and certain fatty acids is not cyclic AMP-mediated. For example, although PGF1alpha and PGF2alpha are much poorer stimulators of cyclic AMP formation than are PGE1 and PGE2, they are nevertheless effective inhibitors of substrate uptake. Adrenaline, a very effective stimulator of cyclic AMP formation in the cells, is not inhibitory. Also, the addition of 8-methylthioadenosine 3':5'-cyclic monophosphate (methylthio cyclic AMP) to the culture, methylthio cyclic AMP decreases the uptake of nucleotides into cultures undergoing active cell division, approximately to values found in quiescent cultures. PGE1 also has this effect on cells undergoing active growth. This gradual decrease is substrate uptake caused by PGE1 appears to be a separate event from its initial rapid inhibition of uptake.", "contents": "Effects of prostaglandin on substrate uptake and cell division in human diploid fibroblasts. PG (prostaglandin) E1 inhibits the uptake of iridine, thymidine, 2-deoxy-D-glucose and L-isoleucine into human diploid WI38 fibroblasts. The inhibition occurs within seconds of the addition of the prostaglandin to the culture. PGE2, PGF1alpha and PGF2alpha behave similarly. Arachidonic acid and 8,11,14-eicosatrienoic acid also decrease uptake in the presence or absence of indomethacin. Other unsaturated fatty acids such as oleic acid, linoleic acid and linolenic acid are essentially inactive. Ricinoleic acid (the 9-hydroxyoleic acid), however, inhibits uptake to about the same degree, at concentrations similar to those of the prostaglandins. Results indicate that this rapid blockage by the prostaglandins and certain fatty acids is not cyclic AMP-mediated. For example, although PGF1alpha and PGF2alpha are much poorer stimulators of cyclic AMP formation than are PGE1 and PGE2, they are nevertheless effective inhibitors of substrate uptake. Adrenaline, a very effective stimulator of cyclic AMP formation in the cells, is not inhibitory. Also, the addition of 8-methylthioadenosine 3':5'-cyclic monophosphate (methylthio cyclic AMP) to the culture, methylthio cyclic AMP decreases the uptake of nucleotides into cultures undergoing active cell division, approximately to values found in quiescent cultures. PGE1 also has this effect on cells undergoing active growth. This gradual decrease is substrate uptake caused by PGE1 appears to be a separate event from its initial rapid inhibition of uptake."}
{"id": "PMID:192205", "title": "Studies on sex-organ development. The hormonal regulation of steroidogenesis and adenosine 3':5'-cyclic monophosphate in embryonic-chick ovary.", "content": "1. We investigated the production of steroid hormones by the ovaries of the developing embryonic chick under conditions of organ culture. Radioimmunoassay techniques were used to measure the amount of steroid hormone released into the culture medium. Stimulation of the production of steroid hormones by choriogonadotropin from the urine of pregnant human was dose-dependent. Oestradio and testosterone production was optimal when 20 i.u. of gonadotropic hormone was present in the culture medium 2. During development, both left and right ovaries responded to gonadotropic hormone stimulation with a 2.5-3-fold increase in oestrogen production. However, the right ovary was twice as efficient in testosterone production as the left one. The presence of dibutyryl cyclic AMP in the culture medium of the embryonic ovaries mimicked the effect of the gonadotropic hormone. 3. The human choriogonadotropic hormone stimulated cyclic AMP production in the embryonic ovarian tissue. Thyrotropin, growth hormone and insulin had no stimulating effect. 3-Isobutyl-1-methylxanthine potentiated the gonadotropic hormone effect by increasing the concentration of cyclic AMP in the ovarian tissue. 4. The amount of cyclic AMP synthesized in the embryonic ovary was gradually increased (from 1.2 to 6.5 pmol/mg of tissue) when incubated with increasing doses of human choriogonadotropic hormone in vitro. The newly synthesized cyclic AMP reached the maximum concnentration after 30 min of incubation, then decreased at 2 h of incubation. A portion of the newly synthesized cyclic AMP was released into the culture medium. 5. At various developmental stages, both left and right embryonic-chick ovaries responded to stimulation by gonadotropic hormone with an increase in cyclic AMP production. The cyclic AMP concentration in the right ovary was 80% higher than that in the corresponding left ovary.", "contents": "Studies on sex-organ development. The hormonal regulation of steroidogenesis and adenosine 3':5'-cyclic monophosphate in embryonic-chick ovary. 1. We investigated the production of steroid hormones by the ovaries of the developing embryonic chick under conditions of organ culture. Radioimmunoassay techniques were used to measure the amount of steroid hormone released into the culture medium. Stimulation of the production of steroid hormones by choriogonadotropin from the urine of pregnant human was dose-dependent. Oestradio and testosterone production was optimal when 20 i.u. of gonadotropic hormone was present in the culture medium 2. During development, both left and right ovaries responded to gonadotropic hormone stimulation with a 2.5-3-fold increase in oestrogen production. However, the right ovary was twice as efficient in testosterone production as the left one. The presence of dibutyryl cyclic AMP in the culture medium of the embryonic ovaries mimicked the effect of the gonadotropic hormone. 3. The human choriogonadotropic hormone stimulated cyclic AMP production in the embryonic ovarian tissue. Thyrotropin, growth hormone and insulin had no stimulating effect. 3-Isobutyl-1-methylxanthine potentiated the gonadotropic hormone effect by increasing the concentration of cyclic AMP in the ovarian tissue. 4. The amount of cyclic AMP synthesized in the embryonic ovary was gradually increased (from 1.2 to 6.5 pmol/mg of tissue) when incubated with increasing doses of human choriogonadotropic hormone in vitro. The newly synthesized cyclic AMP reached the maximum concnentration after 30 min of incubation, then decreased at 2 h of incubation. A portion of the newly synthesized cyclic AMP was released into the culture medium. 5. At various developmental stages, both left and right embryonic-chick ovaries responded to stimulation by gonadotropic hormone with an increase in cyclic AMP production. The cyclic AMP concentration in the right ovary was 80% higher than that in the corresponding left ovary."}
{"id": "PMID:192206", "title": "Hormonal and ionic control of the glycogenolytic cascade in rat liver.", "content": "1. A parallel dose-dependent activation of histone kinase, phosphorylase kinase and phosphorylase was observed in isolated hepatocytes incubated in the presence of glucagon; the effect of suboptimal concentrations of glucagon was antagonized by insulin. 2. An activation of phosphorylase which was not accompanied by a stable change in the activity of phosphorylase kinase was observed in hepatocytes incubated with phenylephrine, isoproterenol or vasopressin as well as on decapitation of unanesthetized animals. A dissociation of the two enzymic activities was also observed in hepatocytes incubated in the presence of a high concentration of glucose, in which phosphorylase was strongly inactivated with no change in the activity of phosphorylase kinase. 3. The activation of phosphorylase by phenylephrine in isolated hepatocytes was counteracted by insulin, greatly decreased by the absence of Ca2+ from the incubation medium, and completely suppressed by the replacement of Na+ by K+. 4. In a liver extract, phosphorylase kinase could also be activated by trypsin. Control, glucagon-activated or trypsin-activated phosphorylase kinase was inhibited by about 70% by EGTA and the activity was restored by the addition of Ca2+. 5. The mechanisms that control the activity of phosphorylase kinase and of phosphorylase are discussed.", "contents": "Hormonal and ionic control of the glycogenolytic cascade in rat liver. 1. A parallel dose-dependent activation of histone kinase, phosphorylase kinase and phosphorylase was observed in isolated hepatocytes incubated in the presence of glucagon; the effect of suboptimal concentrations of glucagon was antagonized by insulin. 2. An activation of phosphorylase which was not accompanied by a stable change in the activity of phosphorylase kinase was observed in hepatocytes incubated with phenylephrine, isoproterenol or vasopressin as well as on decapitation of unanesthetized animals. A dissociation of the two enzymic activities was also observed in hepatocytes incubated in the presence of a high concentration of glucose, in which phosphorylase was strongly inactivated with no change in the activity of phosphorylase kinase. 3. The activation of phosphorylase by phenylephrine in isolated hepatocytes was counteracted by insulin, greatly decreased by the absence of Ca2+ from the incubation medium, and completely suppressed by the replacement of Na+ by K+. 4. In a liver extract, phosphorylase kinase could also be activated by trypsin. Control, glucagon-activated or trypsin-activated phosphorylase kinase was inhibited by about 70% by EGTA and the activity was restored by the addition of Ca2+. 5. The mechanisms that control the activity of phosphorylase kinase and of phosphorylase are discussed."}
{"id": "PMID:192207", "title": "The effect of insulin on the glycogenolytic cascade and on the activity of glycogen synthase in the liver of anaesthetized rabbits.", "content": "1. The administration of insulin to anaesthetized rabbits caused the inactivation of liver phosphorylase and phosphorylase kinase, but did not change either the hepatic concentration of cyclic AMP or the activity of cyclic AMP-dependent histone kinase. All measured parameters were increased by the subsequent administration of glucagon. 2. Activation of glycogen synthase by insulin was only observed when phosphorylase had been strongly inactivated.", "contents": "The effect of insulin on the glycogenolytic cascade and on the activity of glycogen synthase in the liver of anaesthetized rabbits. 1. The administration of insulin to anaesthetized rabbits caused the inactivation of liver phosphorylase and phosphorylase kinase, but did not change either the hepatic concentration of cyclic AMP or the activity of cyclic AMP-dependent histone kinase. All measured parameters were increased by the subsequent administration of glucagon. 2. Activation of glycogen synthase by insulin was only observed when phosphorylase had been strongly inactivated."}
{"id": "PMID:192208", "title": "Phosphorylation of rat thymus histones, its control and the effects thereon of gamma-irradiation.", "content": "The phosphate content of rat thymus histones was determined. As expected for a replicating tissue, histones 1 and 2B were more phosphorylated and had higher 32P uptakes than did histones from resting liver nuclei; the other histones all showed 32P uptake, but the phosphate content and uptake of histone 2A was about half that for liver histone 2A. When thymus nuclei were incubated in a slightly hypo-osmotic medium, non-histone proteins and phosphorylated histones were released into solution; this was enhanced if ATP was present in the medium. [gamma-32P]ATP was incorporated into non-histone proteins, including protein P1, and into the ADP-ribosylated form of histone 1; negligible 32P was incprporated into the other, bound, histones. Histones 1 and 2B added to the incubation medium were extensively, and histones 2A and 4 slightly, phosphorylated. Histones released by increasing the ionic strength of the medium were phosphorylated. Added lysozyme and cytochrome c were neither bound nor phosphorylated, but added non-histone protein P1 was phosphorylated, causing other histones to be released from the nuclei, especially histones 2A and 3. The released histones were phosphorylated. gamma-Irradiation decreased 32P uptake into the non-ADP-ribosylated histones 1 and 4; phosphorylation of histone 1 in vitro was unaffected. The importance of non-histone proteins, ATP availability and nuclear protein kinases to the control of histone phosphorylation in vivo is discussed.", "contents": "Phosphorylation of rat thymus histones, its control and the effects thereon of gamma-irradiation. The phosphate content of rat thymus histones was determined. As expected for a replicating tissue, histones 1 and 2B were more phosphorylated and had higher 32P uptakes than did histones from resting liver nuclei; the other histones all showed 32P uptake, but the phosphate content and uptake of histone 2A was about half that for liver histone 2A. When thymus nuclei were incubated in a slightly hypo-osmotic medium, non-histone proteins and phosphorylated histones were released into solution; this was enhanced if ATP was present in the medium. [gamma-32P]ATP was incorporated into non-histone proteins, including protein P1, and into the ADP-ribosylated form of histone 1; negligible 32P was incprporated into the other, bound, histones. Histones 1 and 2B added to the incubation medium were extensively, and histones 2A and 4 slightly, phosphorylated. Histones released by increasing the ionic strength of the medium were phosphorylated. Added lysozyme and cytochrome c were neither bound nor phosphorylated, but added non-histone protein P1 was phosphorylated, causing other histones to be released from the nuclei, especially histones 2A and 3. The released histones were phosphorylated. gamma-Irradiation decreased 32P uptake into the non-ADP-ribosylated histones 1 and 4; phosphorylation of histone 1 in vitro was unaffected. The importance of non-histone proteins, ATP availability and nuclear protein kinases to the control of histone phosphorylation in vivo is discussed."}
{"id": "PMID:192209", "title": "Collagenase is a component of the specific granules of human neutrophil leucocytes.", "content": "Azurophil and specific granules were isolated from human polymorphonuclear neutrophil leucocytes. Collagenase was almost exclusively a component of the specific granules. This finding is in contrast with the distribution of other proteolytic enzymes, which are localized in the azurophil (or lysosomal) granules.", "contents": "Collagenase is a component of the specific granules of human neutrophil leucocytes. Azurophil and specific granules were isolated from human polymorphonuclear neutrophil leucocytes. Collagenase was almost exclusively a component of the specific granules. This finding is in contrast with the distribution of other proteolytic enzymes, which are localized in the azurophil (or lysosomal) granules."}
{"id": "PMID:192210", "title": "The effects of bathophenanthroline, bathophenanthrolinesulphonate and 2-thenoyltrifluoroacetone on mung-bean mitochondria and submitochondrial particles.", "content": "The effects of bathophenanthroline, bathophenanthrolinesulphonate and 2-thenoyltrifluoroacetone on mung-bean mitochondria and submitochondrial particles were investigated. A variety of inhibitory effects on the oxidations of NADH, succinate and malate were observed. The results are discussed in relation to sites of inhibition and their relation to the effects on mammalian mitochondria.", "contents": "The effects of bathophenanthroline, bathophenanthrolinesulphonate and 2-thenoyltrifluoroacetone on mung-bean mitochondria and submitochondrial particles. The effects of bathophenanthroline, bathophenanthrolinesulphonate and 2-thenoyltrifluoroacetone on mung-bean mitochondria and submitochondrial particles were investigated. A variety of inhibitory effects on the oxidations of NADH, succinate and malate were observed. The results are discussed in relation to sites of inhibition and their relation to the effects on mammalian mitochondria."}
{"id": "PMID:192211", "title": "Factors controlling the activities of phosphatidate phosphohydrolase and phosphatidate cytidylyltransferase. The effects of chlorpromazine, demethylimipramine, cinchocaine, norfenfluramine, mepyramine and magnesium ions.", "content": "1. Microsomal membranes from rat liver were incubated with ATP, CoA, Mg2+, [14C]palmitate, F- and sn-glycerol 3-phosphate in order to label them with [14C]phosphatidate. These membranes were isolated and used in a second incubation in which [3H]CTP was present, and the simultaneous synthesis of [14C]diacylglycerol and [3H]CDP-diacylglycerol was measured. 2. The addition of phosphatidate phosphohydrolase, which had been partially purified from the particle-free supernatant, supplemented the activity of the endogenous phosphohydrolase, but it did not alter the rate of CDP-diacylglycerol formation. 3. Adding EDTA inhibited phosphatidate cytidylyl-transferase activity and stimulated the activity of the phosphohydrolases by removing excess of Mg2+. 4. Increasing the concentration of Mg2+, norfenfluramine or chlorpromazine in the assay system stimulated cytidylyltransferase activity, but decreased the activities of both phosphohydrolases. 5. The mechanism for the stimulation of cytidylyl=transferase activity by the cationic drugs and Mg2+ was investigated with emulsions of phosphatidate and the microsomal fraction of rat liver. 6. There was a threshold concentration of about 5mM-MgCl2 below which no cytidylyltransferase activity was detected in the presence or absence of norfenfluramine. Just above this threshold concentration norfenfluramine stimulated cytidylyltransferase activity, but this stimulation disappeared as the Mg2+ concentration was raised to its optimum of 20mM. Norfenfluramine therefore partially replaced the bivalent-cation requirement. 7. At 30 mM-MgCl2 amphiphilic cationic drugs inhibited cytidylyltransferase activity at relatively high concentrations in a non-competitive manner with respect to phosphatidate. 8. The implications of these results are discussed with respect to the regulation of the synthesis of the acidic phospholipids compared with the synthesis of phosphatidylcholine, phosphatidylethanolamine and triacylglycerol.", "contents": "Factors controlling the activities of phosphatidate phosphohydrolase and phosphatidate cytidylyltransferase. The effects of chlorpromazine, demethylimipramine, cinchocaine, norfenfluramine, mepyramine and magnesium ions. 1. Microsomal membranes from rat liver were incubated with ATP, CoA, Mg2+, [14C]palmitate, F- and sn-glycerol 3-phosphate in order to label them with [14C]phosphatidate. These membranes were isolated and used in a second incubation in which [3H]CTP was present, and the simultaneous synthesis of [14C]diacylglycerol and [3H]CDP-diacylglycerol was measured. 2. The addition of phosphatidate phosphohydrolase, which had been partially purified from the particle-free supernatant, supplemented the activity of the endogenous phosphohydrolase, but it did not alter the rate of CDP-diacylglycerol formation. 3. Adding EDTA inhibited phosphatidate cytidylyl-transferase activity and stimulated the activity of the phosphohydrolases by removing excess of Mg2+. 4. Increasing the concentration of Mg2+, norfenfluramine or chlorpromazine in the assay system stimulated cytidylyltransferase activity, but decreased the activities of both phosphohydrolases. 5. The mechanism for the stimulation of cytidylyl=transferase activity by the cationic drugs and Mg2+ was investigated with emulsions of phosphatidate and the microsomal fraction of rat liver. 6. There was a threshold concentration of about 5mM-MgCl2 below which no cytidylyltransferase activity was detected in the presence or absence of norfenfluramine. Just above this threshold concentration norfenfluramine stimulated cytidylyltransferase activity, but this stimulation disappeared as the Mg2+ concentration was raised to its optimum of 20mM. Norfenfluramine therefore partially replaced the bivalent-cation requirement. 7. At 30 mM-MgCl2 amphiphilic cationic drugs inhibited cytidylyltransferase activity at relatively high concentrations in a non-competitive manner with respect to phosphatidate. 8. The implications of these results are discussed with respect to the regulation of the synthesis of the acidic phospholipids compared with the synthesis of phosphatidylcholine, phosphatidylethanolamine and triacylglycerol."}
{"id": "PMID:192212", "title": "Inhibition of lipogenesis by halothane in isolated rat liver cells.", "content": "1. Halothane at clinically effective concentrations [2.5 and 4% (v/v) of the gas phase of the incubation flask] was found to inhibit significantly lipogenesis from endogenous substrates, e.g., glycogen, or from added lactate plus pyruvate. This was accompanied by a decrease in the ratio of the free [NAD+]/[NADH] of the mitochondrion and the cytoplasm, as shown by the [3-hydroxybutyrate]/[acetoacetate] ratio and the [lactate]/[pyruvate] ratio. 2. Acetoacetate or pyruvate decreased the inhibitory effect of halothane and restored lipogenesis to control rates. They were reduced rapidly by 3-hydroxybutyrate dehydrogenase or lactate dehydrogenase respectively, with the concomitant oxidation of NADH and the generation of NAD+. 3. These results suggest that the mechanism by which halothane inhibits lipogenesis from glycogen or lactate is by inhibition of the oxidation of NADH; this results in inhibition of flux of carbon through pyruvate dehydrogenase and a shortage of acetyl-CoA for fatty acid synthesis. Thus when NADH acceptors are added in the presence of halothane, the concentration of mitochondrial NAD+ is raised so that the flux of carbon through pyruvate dehydrogenase increases and lipogenesis is restored.", "contents": "Inhibition of lipogenesis by halothane in isolated rat liver cells. 1. Halothane at clinically effective concentrations [2.5 and 4% (v/v) of the gas phase of the incubation flask] was found to inhibit significantly lipogenesis from endogenous substrates, e.g., glycogen, or from added lactate plus pyruvate. This was accompanied by a decrease in the ratio of the free [NAD+]/[NADH] of the mitochondrion and the cytoplasm, as shown by the [3-hydroxybutyrate]/[acetoacetate] ratio and the [lactate]/[pyruvate] ratio. 2. Acetoacetate or pyruvate decreased the inhibitory effect of halothane and restored lipogenesis to control rates. They were reduced rapidly by 3-hydroxybutyrate dehydrogenase or lactate dehydrogenase respectively, with the concomitant oxidation of NADH and the generation of NAD+. 3. These results suggest that the mechanism by which halothane inhibits lipogenesis from glycogen or lactate is by inhibition of the oxidation of NADH; this results in inhibition of flux of carbon through pyruvate dehydrogenase and a shortage of acetyl-CoA for fatty acid synthesis. Thus when NADH acceptors are added in the presence of halothane, the concentration of mitochondrial NAD+ is raised so that the flux of carbon through pyruvate dehydrogenase increases and lipogenesis is restored."}
{"id": "PMID:192213", "title": "Acetylcholine increases the breakdown of triphosphoinositide of rabbit iris muscle prelabelled with [32P] phosphate.", "content": "1. Paired iris smooth muscles from rabbits were incubated for 30 min at 37 degrees C in an iso-osmotic salt medium containg glucose, inositol, cytidine and [32P]phosphate. 2. One of the pair was then incubated at 37 degrees C for 10 min in unlabelled medium containing 10mM-2-deoxyglucose and the other was incubated in the presence of acetylcholine plus eserine (0.05mM each). 2-Deoxyglucose, which was included in the incubation medium to minimize the biosynthesis of triphosphoinositide from ATP and diphosphoinositide, decreased the amount of labelled ATP by 71% and inhibited further 32P incorporation from ATP into triphosphoinositide by almost 30%. 3. Acetylcholine (0.05mM) increased significantly the loss of 32P from triphosphoinositide (the 'triphosphoinositide effect') in 32P-labelled iris muscle. This effect was measured both chemically and radiochemically. It was also observed when 32Pi was replaced by myo-[3H]inositol in the incubation medium. 4. The triphosphoinositide effect was blocked by atropine but not by D-tubocurarine. Further, muscarinic but not nicotinic agonists were found to provoke this effect. 5. Acetylcholine decreased by 28% the 32P incorporation into triphosphoinositide, presumably by stimulating its breakdown. This decrement in triphosphoinositide was blocked by atropine, but not by D-tubocurarine. 6. The triphosphoinositide effect was accompanied by a significant increase in 32P labelling, but not tissue concentration, of phosphatidylinositol and phosphatidic acid. The possible relationship between the loss of 32P label from triphosphoinositide in response to acetylcholine and the concomitant increase in that of phosphatidylinositol and phosphatidic acid is discussed. 7. The presence of triphosphoinositide phosphomonoesterase, the enzyme that might be stimulated in the iris smooth muscle by the neurotransmitter, was demonstrated, and, under our methods of homogenization and assay, more than 80% of its activity was localized in the particulate fraction.", "contents": "Acetylcholine increases the breakdown of triphosphoinositide of rabbit iris muscle prelabelled with [32P] phosphate. 1. Paired iris smooth muscles from rabbits were incubated for 30 min at 37 degrees C in an iso-osmotic salt medium containg glucose, inositol, cytidine and [32P]phosphate. 2. One of the pair was then incubated at 37 degrees C for 10 min in unlabelled medium containing 10mM-2-deoxyglucose and the other was incubated in the presence of acetylcholine plus eserine (0.05mM each). 2-Deoxyglucose, which was included in the incubation medium to minimize the biosynthesis of triphosphoinositide from ATP and diphosphoinositide, decreased the amount of labelled ATP by 71% and inhibited further 32P incorporation from ATP into triphosphoinositide by almost 30%. 3. Acetylcholine (0.05mM) increased significantly the loss of 32P from triphosphoinositide (the 'triphosphoinositide effect') in 32P-labelled iris muscle. This effect was measured both chemically and radiochemically. It was also observed when 32Pi was replaced by myo-[3H]inositol in the incubation medium. 4. The triphosphoinositide effect was blocked by atropine but not by D-tubocurarine. Further, muscarinic but not nicotinic agonists were found to provoke this effect. 5. Acetylcholine decreased by 28% the 32P incorporation into triphosphoinositide, presumably by stimulating its breakdown. This decrement in triphosphoinositide was blocked by atropine, but not by D-tubocurarine. 6. The triphosphoinositide effect was accompanied by a significant increase in 32P labelling, but not tissue concentration, of phosphatidylinositol and phosphatidic acid. The possible relationship between the loss of 32P label from triphosphoinositide in response to acetylcholine and the concomitant increase in that of phosphatidylinositol and phosphatidic acid is discussed. 7. The presence of triphosphoinositide phosphomonoesterase, the enzyme that might be stimulated in the iris smooth muscle by the neurotransmitter, was demonstrated, and, under our methods of homogenization and assay, more than 80% of its activity was localized in the particulate fraction."}
{"id": "PMID:192214", "title": "The oxidation-reduction potential of the reaction-centre chlorophyll (P700) in Photosystem I. Evidence for multiple components in electron-paramagnetic-resonance signal 1 at low temperature.", "content": "The oxidation-reduction potential of the reaction-centre chlorophyll of Photosystem I (P700) in spinach chloroplasts was determined by using the ability of the reaction centre to photoreduce the bound ferredoxin and to photo-oxidize P700 on illumination at 20K as an indicator of the oxidation state of P700. This procedure shows that P700 is oxidized with Em (pH8.0)(mid-point redox potential at pH8.0)congruent to +375mV. Further oxidation of the chloroplast preparations by high concentrations of K3Fe(CN)6(10mM) in the presence of mediating dyes leads to the appearance of a large radical signal with an apparent Em congruent to +470mVA second, light-inducible, radical also appears over the same potential range. We propose that these signals are due to bulk chlorophyll oxidation and not, as was previously thought [Knaff & Malkin (1973) Arch. Biochem. Biophys. 159, 555-562], to reaction-centre oxidation. A number of optical techniques were used to determine Em of P700. Dual-wavelength spectroscopy (697-720nm) indicates Em congruent to +460-+480mV. The spectrum of the sample during the titration showed a large contribution to the signal by bulk chlorophyll oxidation, in agreement with the electron-paramagnetic-resonance results and those of Ke, Sugahara & Shaw [(1975) Biochim. Biophys. Acta 408, 12-25]. The light-induced absorbance change at 435 nm, usually attributed to P700, showed a potential dependence similar to that of bulk chlorophyll oxidation. Determination of Em of P700 on the basis of the appearance of the P700 signal in oxidized-versus-reduced difference spectra showed Em (pH8.0) congruent to +360mV. Measurements of the effect of potential on the irreversible photo-oxidation of P700 at 77K showed that P700 became oxidized in this potential range. We conclude that the reaction-centre chlorophyll of Photosystem I has Em (pH8.0) congruent to +375mV.", "contents": "The oxidation-reduction potential of the reaction-centre chlorophyll (P700) in Photosystem I. Evidence for multiple components in electron-paramagnetic-resonance signal 1 at low temperature. The oxidation-reduction potential of the reaction-centre chlorophyll of Photosystem I (P700) in spinach chloroplasts was determined by using the ability of the reaction centre to photoreduce the bound ferredoxin and to photo-oxidize P700 on illumination at 20K as an indicator of the oxidation state of P700. This procedure shows that P700 is oxidized with Em (pH8.0)(mid-point redox potential at pH8.0)congruent to +375mV. Further oxidation of the chloroplast preparations by high concentrations of K3Fe(CN)6(10mM) in the presence of mediating dyes leads to the appearance of a large radical signal with an apparent Em congruent to +470mVA second, light-inducible, radical also appears over the same potential range. We propose that these signals are due to bulk chlorophyll oxidation and not, as was previously thought [Knaff & Malkin (1973) Arch. Biochem. Biophys. 159, 555-562], to reaction-centre oxidation. A number of optical techniques were used to determine Em of P700. Dual-wavelength spectroscopy (697-720nm) indicates Em congruent to +460-+480mV. The spectrum of the sample during the titration showed a large contribution to the signal by bulk chlorophyll oxidation, in agreement with the electron-paramagnetic-resonance results and those of Ke, Sugahara & Shaw [(1975) Biochim. Biophys. Acta 408, 12-25]. The light-induced absorbance change at 435 nm, usually attributed to P700, showed a potential dependence similar to that of bulk chlorophyll oxidation. Determination of Em of P700 on the basis of the appearance of the P700 signal in oxidized-versus-reduced difference spectra showed Em (pH8.0) congruent to +360mV. Measurements of the effect of potential on the irreversible photo-oxidation of P700 at 77K showed that P700 became oxidized in this potential range. We conclude that the reaction-centre chlorophyll of Photosystem I has Em (pH8.0) congruent to +375mV."}
{"id": "PMID:192215", "title": "Alloxan cytotoxicity in vitro. Inhibition of rubidium ion pumping in pancreatic beta-cells.", "content": "Exposing micro-dissected pancreatic islets of non-inbred ob/ob mice to 2-5 mM-alloxan for 10 min decreased the ability of the islets to accumulate Rb+. Rb+ accumulation in pieces of exocrine pancreas was unaffected by alloxan. When islets were treated with alloxan in the presence of 2-20 mM-D-glucose, the Rb+-accumulating ability was protected in a dose-dependent manner. The protective action of D-glucose was reproduced with 3-O-methyl-D-glucose but not with L-glucose or D-mannoheptulose; mannoheptulose prevented D-glucose from exerting its protective action. The inhibition of Rb+ accumulation was due to a decreased inward pumping, since alloxan did not affect Rb+ efflux from pre-loaded islets. The inhibitory effect of alloxan had a latency of about 1 min, as revealed by experiments with dispersed islet cells in suspension. Alloxan-treated islets showed only a marginal decrease in ATP and no change in glucose 6-phosphate concentration. Although alloxan slightly decreased the hydrolysis of ATP in a subcellular fraction enriched in plasma membranes, this effect could not be attributed to a ouabain-sensitive adenosine triphosphatase. The plasma membranes exhibited a K+-activated hydrolysis of p-nitrophenyl phosphate; this enzyme activity too was insensitive to alloxan. Glucose may protect the univalent-cation pump by preventing permeation of alloxan via a path coupled to the hexose-transport system. Inhibition of the pump may be fundamental to the induction of alloxan-diabetes.", "contents": "Alloxan cytotoxicity in vitro. Inhibition of rubidium ion pumping in pancreatic beta-cells. Exposing micro-dissected pancreatic islets of non-inbred ob/ob mice to 2-5 mM-alloxan for 10 min decreased the ability of the islets to accumulate Rb+. Rb+ accumulation in pieces of exocrine pancreas was unaffected by alloxan. When islets were treated with alloxan in the presence of 2-20 mM-D-glucose, the Rb+-accumulating ability was protected in a dose-dependent manner. The protective action of D-glucose was reproduced with 3-O-methyl-D-glucose but not with L-glucose or D-mannoheptulose; mannoheptulose prevented D-glucose from exerting its protective action. The inhibition of Rb+ accumulation was due to a decreased inward pumping, since alloxan did not affect Rb+ efflux from pre-loaded islets. The inhibitory effect of alloxan had a latency of about 1 min, as revealed by experiments with dispersed islet cells in suspension. Alloxan-treated islets showed only a marginal decrease in ATP and no change in glucose 6-phosphate concentration. Although alloxan slightly decreased the hydrolysis of ATP in a subcellular fraction enriched in plasma membranes, this effect could not be attributed to a ouabain-sensitive adenosine triphosphatase. The plasma membranes exhibited a K+-activated hydrolysis of p-nitrophenyl phosphate; this enzyme activity too was insensitive to alloxan. Glucose may protect the univalent-cation pump by preventing permeation of alloxan via a path coupled to the hexose-transport system. Inhibition of the pump may be fundamental to the induction of alloxan-diabetes."}
{"id": "PMID:192216", "title": "A phosphodiesterase in rat kidney cortex that hydrolyses glycerylphosphorylinositol.", "content": "1. A phosphodiesterase, active at an alkaline pH, is present in the outer cortex of rat kidney and hydrolyses glycerylphosphorylinositol into glycerol and phosphorylinositol. Some inositol cyclic phosphate can also be formed indicating that the enzyme can act as a cyclizing phosphotransferase. 2. The enzyme is stimulated by Ca2+(2-3mM) whereas Mg2+ is inhibitory. 3. The activity is markedly stimulated by low concentrations of thiol reagents (1-2mM) such as cysteine or dithiothreitol. 4. The properties of the enzyme have been compared with glycerylphosphinicocholine diesterase (EC 3.1.4.2), which is also present in the isolated enzyme complex, and it is concluded that the enzymes have separate identities.", "contents": "A phosphodiesterase in rat kidney cortex that hydrolyses glycerylphosphorylinositol. 1. A phosphodiesterase, active at an alkaline pH, is present in the outer cortex of rat kidney and hydrolyses glycerylphosphorylinositol into glycerol and phosphorylinositol. Some inositol cyclic phosphate can also be formed indicating that the enzyme can act as a cyclizing phosphotransferase. 2. The enzyme is stimulated by Ca2+(2-3mM) whereas Mg2+ is inhibitory. 3. The activity is markedly stimulated by low concentrations of thiol reagents (1-2mM) such as cysteine or dithiothreitol. 4. The properties of the enzyme have been compared with glycerylphosphinicocholine diesterase (EC 3.1.4.2), which is also present in the isolated enzyme complex, and it is concluded that the enzymes have separate identities."}
{"id": "PMID:192217", "title": "Protein determinants of myelination in different regions of developing rat central nervous system.", "content": "Measurements of several different protein determinants correlated with the time and rate of myelination in five areas of the central nervous system are presented. The deposition of protein in the subcellular fraction corresponding to the density of adult myelin, the appearance of basic protein characteristic myelin, the change in proportions of the individual myelin proteins, the appearance and distribution of the myelin marker 2':3'-cyclic nucleotide3'-phosphohydrolase, and the results of morphological studies of purified myelin are compared. According to these various criteria, and in agreement with the morphological observations of others, myelin appears earliest in the spinal cord, then in the brain stem, and latest in the cerebral hemispheres. Multilamellar myelin was observed in the rat brain stem and spinal cord as early as 5 days of age. The relative proportion of the individual myelin proteins changed with myelin maturation in all areas, with the larger basic protein decreasing reciprocally with increase of the smaller basic protein. The proportion of Wolfgram protein also decreased with maturation. Larger proportions of the enzyme 2':3'-cyclic nucleotide 3'-phosphohydrolase were located in the microsomal fraction at early ages. During development the enzyme activity gradually became associated more with a fraction of a density corresponding to adult myelin, suggesting the presence of precursor membrane fragments in microsomal fractions in the early stages of myelination before compact myelin formation. A significant proportion of the total nucleotide phosphohydrolase activity of the homogenate could not be recovered in subcellular fraction at early ages, but the recovers of the enzyme increased with maturation and the activity was found more in the myelin fraction.", "contents": "Protein determinants of myelination in different regions of developing rat central nervous system. Measurements of several different protein determinants correlated with the time and rate of myelination in five areas of the central nervous system are presented. The deposition of protein in the subcellular fraction corresponding to the density of adult myelin, the appearance of basic protein characteristic myelin, the change in proportions of the individual myelin proteins, the appearance and distribution of the myelin marker 2':3'-cyclic nucleotide3'-phosphohydrolase, and the results of morphological studies of purified myelin are compared. According to these various criteria, and in agreement with the morphological observations of others, myelin appears earliest in the spinal cord, then in the brain stem, and latest in the cerebral hemispheres. Multilamellar myelin was observed in the rat brain stem and spinal cord as early as 5 days of age. The relative proportion of the individual myelin proteins changed with myelin maturation in all areas, with the larger basic protein decreasing reciprocally with increase of the smaller basic protein. The proportion of Wolfgram protein also decreased with maturation. Larger proportions of the enzyme 2':3'-cyclic nucleotide 3'-phosphohydrolase were located in the microsomal fraction at early ages. During development the enzyme activity gradually became associated more with a fraction of a density corresponding to adult myelin, suggesting the presence of precursor membrane fragments in microsomal fractions in the early stages of myelination before compact myelin formation. A significant proportion of the total nucleotide phosphohydrolase activity of the homogenate could not be recovered in subcellular fraction at early ages, but the recovers of the enzyme increased with maturation and the activity was found more in the myelin fraction."}
{"id": "PMID:192218", "title": "Changes in enzymic activities of nucleoside diphosphate sugar interconversions during differentiation of cambium to xylem in sycamore and poplar.", "content": "During the transition from primary wall formation to secondary thickening there is a marked shift in the synthesis of pectin, hemicellulose and cellulose. The activities of the enzymes [UDP-D-galactose 4-epimerase (EC 5.1.3.2)8 UDP-l-arabinose 4-epimerase (EC 5.1.3.5), UDP-D-glucose dehydrogenase (EC 1.1.1.22) and UDP-D--glucuronate decarboxylase (EC 4.1.1.35)] were measured in cambial cells, differentiating xylem cells and differentiated xylem cells isolated from sycamore and poplar trees, and phloem cells from poplar. At the final stage of the differentiation of cambium to xylem there was a decrease in activity of the enzymes directly involved in producing the soluble precursors of pectin (DUP-D-galactose 4-epimerase and UDP-L-arabinose 4-epimerase and an increase in those producing the precursors of hemicellulose (UDP-D-glucose dehydrogenase and UDP-D-glucuronate decarboxylase). These results strongly suggest ahat the changes were correlated with the differences observed in the chemical composition of the wall during development. The changes found in the catalytic activity of the enzymes of nucleoside diphosphate sugar interconversion exert a coarse control over the synthesis of pectin and hemicelluloses. The tissues at all stages of development contained the necessary enzyme activities to produce all the precursors of pectin and hemicellulose, even at the final stage of differentiation when no pectin was formed.", "contents": "Changes in enzymic activities of nucleoside diphosphate sugar interconversions during differentiation of cambium to xylem in sycamore and poplar. During the transition from primary wall formation to secondary thickening there is a marked shift in the synthesis of pectin, hemicellulose and cellulose. The activities of the enzymes [UDP-D-galactose 4-epimerase (EC 5.1.3.2)8 UDP-l-arabinose 4-epimerase (EC 5.1.3.5), UDP-D-glucose dehydrogenase (EC 1.1.1.22) and UDP-D--glucuronate decarboxylase (EC 4.1.1.35)] were measured in cambial cells, differentiating xylem cells and differentiated xylem cells isolated from sycamore and poplar trees, and phloem cells from poplar. At the final stage of the differentiation of cambium to xylem there was a decrease in activity of the enzymes directly involved in producing the soluble precursors of pectin (DUP-D-galactose 4-epimerase and UDP-L-arabinose 4-epimerase and an increase in those producing the precursors of hemicellulose (UDP-D-glucose dehydrogenase and UDP-D-glucuronate decarboxylase). These results strongly suggest ahat the changes were correlated with the differences observed in the chemical composition of the wall during development. The changes found in the catalytic activity of the enzymes of nucleoside diphosphate sugar interconversion exert a coarse control over the synthesis of pectin and hemicelluloses. The tissues at all stages of development contained the necessary enzyme activities to produce all the precursors of pectin and hemicellulose, even at the final stage of differentiation when no pectin was formed."}
{"id": "PMID:192219", "title": "Changes in enzymic activities of nucleoside diphosphate sugar interconversions during differentiation of cambium to xylem in pine and fir.", "content": "A protein fraction [precipitate obtained between 40 and 65% (NH4)2SO4 satn.] prepared from cambial cells, differentiating xylem cells and differentiated xylem cells of pine and fir trees contained all the enzymes required for the nucleoside diphosphate sugar interconversions. By using UDP-D-[U-14C]glucose or UDP-D-[U-14C]galactose, UDP-D-[U-14C-]glucuronic acid and UDP-D-[U-14C]xylose as substrates, the activities of UDP-D-galactose 4-epimerase (DC 5.1.3.2), UDP-D-xylose 4-epimerase(EC 5.1.3.5), UDP-D-glucose dehydrogenase (EC 1.1.1.22) and UDP-D-glucuronate 4-epimerase (EC5.1.3.6), UDP-d-glucuronate decarboxylase (EC 4.1.1.35) were measured at different stages of cell-wall development. The specific activities and the activities per cell of these enzymes varied during differentiation of cambium to xylem according to the type polysaccharide synthesized. Variations were also found between the two species investigated. These data, compared with those obtained in out previous work on angiosperms [see the preceding paper, Dalessandro & Northcote (1977) Biochem. J. 162, 267-279], suggest that some control of polysaccharide synthesis operates at the level of the formation of the precursors of pectin and hemicellulose syntheses.", "contents": "Changes in enzymic activities of nucleoside diphosphate sugar interconversions during differentiation of cambium to xylem in pine and fir. A protein fraction [precipitate obtained between 40 and 65% (NH4)2SO4 satn.] prepared from cambial cells, differentiating xylem cells and differentiated xylem cells of pine and fir trees contained all the enzymes required for the nucleoside diphosphate sugar interconversions. By using UDP-D-[U-14C]glucose or UDP-D-[U-14C]galactose, UDP-D-[U-14C-]glucuronic acid and UDP-D-[U-14C]xylose as substrates, the activities of UDP-D-galactose 4-epimerase (DC 5.1.3.2), UDP-D-xylose 4-epimerase(EC 5.1.3.5), UDP-D-glucose dehydrogenase (EC 1.1.1.22) and UDP-D-glucuronate 4-epimerase (EC5.1.3.6), UDP-d-glucuronate decarboxylase (EC 4.1.1.35) were measured at different stages of cell-wall development. The specific activities and the activities per cell of these enzymes varied during differentiation of cambium to xylem according to the type polysaccharide synthesized. Variations were also found between the two species investigated. These data, compared with those obtained in out previous work on angiosperms [see the preceding paper, Dalessandro & Northcote (1977) Biochem. J. 162, 267-279], suggest that some control of polysaccharide synthesis operates at the level of the formation of the precursors of pectin and hemicellulose syntheses."}
{"id": "PMID:192220", "title": "Effects of anti-microtubular agents and cycloheximide on the metabolism of chylomicron cholesteryl esters by hepatocyte suspensions.", "content": "1. Post-heparin plasma that promoted rapid hydrolysis of about 90% of the triacylglycerol markedly stimulated the uptake or binding of chylomicron cholesteryl ester by suspended hepatocytes. The net hydrolysis of chyle cholesteryl ester after the uptake by the cells was, however, slower than in vivo. 2. The cholesteryl ester uptake in the presence of post-heparin plasma was larger if the cells had been preincubated for 2h. It was inhibited by the presence of colchicine, vinblastine or cycloheximide during the preincubation, and by mild trypsin treatment of the preincubated cells. 3. The results suggested that the anti-microtubular agents, but not cycloheximide, also inhibited the hydrolysis of chyle cholesteryl ester after uptake or binding to the cells. 4. The uptake of isolated chylomicron remnant particles was more efficient than that of native chyle lipoproteins. It was, however, still stimulated by heparin alone and by post-heparin plasma. The heparin-stimulated uptake was markedly decreased if cycloheximide was present during the preincubation period.", "contents": "Effects of anti-microtubular agents and cycloheximide on the metabolism of chylomicron cholesteryl esters by hepatocyte suspensions. 1. Post-heparin plasma that promoted rapid hydrolysis of about 90% of the triacylglycerol markedly stimulated the uptake or binding of chylomicron cholesteryl ester by suspended hepatocytes. The net hydrolysis of chyle cholesteryl ester after the uptake by the cells was, however, slower than in vivo. 2. The cholesteryl ester uptake in the presence of post-heparin plasma was larger if the cells had been preincubated for 2h. It was inhibited by the presence of colchicine, vinblastine or cycloheximide during the preincubation, and by mild trypsin treatment of the preincubated cells. 3. The results suggested that the anti-microtubular agents, but not cycloheximide, also inhibited the hydrolysis of chyle cholesteryl ester after uptake or binding to the cells. 4. The uptake of isolated chylomicron remnant particles was more efficient than that of native chyle lipoproteins. It was, however, still stimulated by heparin alone and by post-heparin plasma. The heparin-stimulated uptake was markedly decreased if cycloheximide was present during the preincubation period."}
{"id": "PMID:192221", "title": "Effect of thyroliberin on the concentration of adenosine 3':5'-phosphate and on the activity of adenosine 3':5'-phosphate-dependent protein kinase in prolactin-producing cells in culture.", "content": "1. The effects of thyroliberin were studied in cultured rat pituitary-tumour cells that synthesize and secrete prolactin (the GH4C1 cell strain). 2. Prolactin and cyclic AMP were measured by radioimmunological methods, and a cyclic AMP-dependent protein kinase was characterized by using histone as substrate. 3. Prolactin release was studied after 5-60min of treatment, and synthesis after 48h of treatment with thyroliberin. One-half maximum stimulation of release and synthesis were observed at 0.25 and at 4nM respectively. 4. Cyclic AMP was temporarily increased in cell suspensions after treatment with thyroliberin, and one-half maximum stimulation was observed at 25nM. 5. Dibutyryl cyclic AMP increased prolactin release and synthesis, one-half maximum effects being obtained at 20 micronM. 6. A cyclic AMP-dependent protein kinase, which was one-half maximally stimulated at 30 nM-cyclic AMP, was demonstrated. 7. An increase in the activity ratio (-cyclic AMP/+cyclic AMP) of the cyclic AMP-dependent protein kinase was observed after treatment with thyroliberin. Total protein kinase activity in the presence of cyclic AMP was unaltered. The time-course of enzyme activation was similar to that of cyclic AMP formation and corresponded to the time when prolactin release was first observed. 8. It is concluded that thyroliberin induces cyclic AMP formation, resulting in the activation of a cyclic AMP-dependent protein kinase.", "contents": "Effect of thyroliberin on the concentration of adenosine 3':5'-phosphate and on the activity of adenosine 3':5'-phosphate-dependent protein kinase in prolactin-producing cells in culture. 1. The effects of thyroliberin were studied in cultured rat pituitary-tumour cells that synthesize and secrete prolactin (the GH4C1 cell strain). 2. Prolactin and cyclic AMP were measured by radioimmunological methods, and a cyclic AMP-dependent protein kinase was characterized by using histone as substrate. 3. Prolactin release was studied after 5-60min of treatment, and synthesis after 48h of treatment with thyroliberin. One-half maximum stimulation of release and synthesis were observed at 0.25 and at 4nM respectively. 4. Cyclic AMP was temporarily increased in cell suspensions after treatment with thyroliberin, and one-half maximum stimulation was observed at 25nM. 5. Dibutyryl cyclic AMP increased prolactin release and synthesis, one-half maximum effects being obtained at 20 micronM. 6. A cyclic AMP-dependent protein kinase, which was one-half maximally stimulated at 30 nM-cyclic AMP, was demonstrated. 7. An increase in the activity ratio (-cyclic AMP/+cyclic AMP) of the cyclic AMP-dependent protein kinase was observed after treatment with thyroliberin. Total protein kinase activity in the presence of cyclic AMP was unaltered. The time-course of enzyme activation was similar to that of cyclic AMP formation and corresponded to the time when prolactin release was first observed. 8. It is concluded that thyroliberin induces cyclic AMP formation, resulting in the activation of a cyclic AMP-dependent protein kinase."}
{"id": "PMID:192222", "title": "Surface components involved in virally mediated membrane changes.", "content": "1. Virally mediated permeability changes are not brought about by neuraminidase or other enzyme. They are not mimicked by local anaesthetics such as benzyl alcohol or dibucaine. 2. Virus induces an increase in the exchange rate of membrane-bound Ca2+. The temperature-dependence, and sensitivity to concanavalin A, of the permeability change and of Ca2+ exchange are similar. 3. It is concluded that an increase in the exchangeability of membrane-bound Ca2+ constitutes an early and specific event after the attachment of Sendai virus to cultured cells.", "contents": "Surface components involved in virally mediated membrane changes. 1. Virally mediated permeability changes are not brought about by neuraminidase or other enzyme. They are not mimicked by local anaesthetics such as benzyl alcohol or dibucaine. 2. Virus induces an increase in the exchange rate of membrane-bound Ca2+. The temperature-dependence, and sensitivity to concanavalin A, of the permeability change and of Ca2+ exchange are similar. 3. It is concluded that an increase in the exchangeability of membrane-bound Ca2+ constitutes an early and specific event after the attachment of Sendai virus to cultured cells."}
{"id": "PMID:192223", "title": "The substrate specificity of adenosine 3':5'-cyclic monophosphate-dependent protein kinase of rabbit skeletal muscle.", "content": "The known amino acid sequences at the two sites on phosphorylase kinase that are phosphorylated by cyclic AMP-dependent protein kinase were extended. The sequences of 42 amino acids around the phosphorylation site on the alpha-subunit and of 14 amino acids around the phosphorylation site on the beta-subunit were shown to be: alpha-subunit Phe-Arg-Arg-Leu-Ser(P)-Ile-Ser-Thr-Glu-Ser-Glx-Pro-Asx-Gly-Gly-His-Ser-Leu-Gly-Ala-Asp-Leu-Met-Ser-Pro-Ser-Phe-Leu-Ser-Pro-Gly-Thr-Ser-Val-Phe(Ser,Pro,Gly)His-Thr-Ser-Lys; beta-subunit, Ala-Arg-Thr-Lys-Arg-Ser-Gly-Ser(P)-VALIle-Tyr-Glu-Pro-Leu-Lys. The sites on histone H2B which are phosphorylated by cyclic AMP-dependent protein kinase in vitro were identified as serine-36 and serine-32. The amino acid sequence in this region is: Lys-Lys-Arg-Lys-Arg-Ser32(P)-Arg-Lys-Glu-Ser36(P)-Tyr-Ser-Val-Tyr-Val- [Iwai, K., Ishikawa, K. & Hayashi, H. (1970) Nature (London) 226, 1056-1058]. Serine-36 was phosphorylated at 50% of the rate at which the beta-subunit of phosphorylase kinase was phosphorylated, and it was phosphorylated 6-7-fold more rapidly than was serine-32. The amino acid sequences when compared with those at the phosphorylation sites of other physiological substrates suggest that the presence of two adjacent basic amino acids on the N-terminal side of the susceptible serine residue may be critical for specific substrate recognition in vivo.", "contents": "The substrate specificity of adenosine 3':5'-cyclic monophosphate-dependent protein kinase of rabbit skeletal muscle. The known amino acid sequences at the two sites on phosphorylase kinase that are phosphorylated by cyclic AMP-dependent protein kinase were extended. The sequences of 42 amino acids around the phosphorylation site on the alpha-subunit and of 14 amino acids around the phosphorylation site on the beta-subunit were shown to be: alpha-subunit Phe-Arg-Arg-Leu-Ser(P)-Ile-Ser-Thr-Glu-Ser-Glx-Pro-Asx-Gly-Gly-His-Ser-Leu-Gly-Ala-Asp-Leu-Met-Ser-Pro-Ser-Phe-Leu-Ser-Pro-Gly-Thr-Ser-Val-Phe(Ser,Pro,Gly)His-Thr-Ser-Lys; beta-subunit, Ala-Arg-Thr-Lys-Arg-Ser-Gly-Ser(P)-VALIle-Tyr-Glu-Pro-Leu-Lys. The sites on histone H2B which are phosphorylated by cyclic AMP-dependent protein kinase in vitro were identified as serine-36 and serine-32. The amino acid sequence in this region is: Lys-Lys-Arg-Lys-Arg-Ser32(P)-Arg-Lys-Glu-Ser36(P)-Tyr-Ser-Val-Tyr-Val- [Iwai, K., Ishikawa, K. & Hayashi, H. (1970) Nature (London) 226, 1056-1058]. Serine-36 was phosphorylated at 50% of the rate at which the beta-subunit of phosphorylase kinase was phosphorylated, and it was phosphorylated 6-7-fold more rapidly than was serine-32. The amino acid sequences when compared with those at the phosphorylation sites of other physiological substrates suggest that the presence of two adjacent basic amino acids on the N-terminal side of the susceptible serine residue may be critical for specific substrate recognition in vivo."}
{"id": "PMID:192224", "title": "Comparison of the substrate specificities of protein phosphatases involved in the regulation of glycogen metabolism in rabbit skeletal muscle.", "content": "Muscle extracts were subjected to fractionation with ethanol, chromatography on DEAE-cellulose, precipitation with (NH4)2SO4 and gel filtration on Sephadex G-200. These fractions were assayed for protein phosphatase activities by using the following seven phosphoprotein substrates: phosphorylase a, glycogen synthase b1, glycogen synthase b2, phosphorylase kinase (phosphorylated in either the alpha-subunit or the beta-subunit), histone H1 and histone H2B. Three protein phosphatases with distinctive specificities were resolved by the final gel-filtration step and were termed I, II and III. Protein phosphatase-I, apparent mol.wt. 300000, was an active histone phosphatase, but it accounted for only 10-15% of the glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities and 2-3% of the phosphorylase kinase phosphatase and phosphorylase phosphatase activity recovered from the Sephadex G-200 column. Protein phosphatase-II, apparent mol.wt. 170000, possessed histone phosphatase activity similar to that of protein phosphatase-I. It possessed more than 95% of the activity towards the alpha-subunit of phosphorylase kinase that was recovered from Sephadex G-200. It accounted for 10-15% of the glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activity, but less than 5% of the activity against the beta-subunit of phosphorylase kinase and 1-2% of the phosphorylase phosphatase activity recovered from Sephadex G-200. Protein phosphatase-III was the most active histone phosphatase. It possessed 95% of the phosphorylase phosphatase and beta-phosphorylase kinase phosphatase activities, and 75% of the glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities recovered from Sephadex G-200. It accounted for less than 5% of the alpha-phosphorylase kinase phosphatase activity. Protein phosphatase-III was sometimes eluted from Sephadex-G-200 as a species of apparent mol.wt. 75000(termed IIIA), sometimes as a species of mol.wt. 46000(termed IIIB) and sometimes as a mixture of both components. The substrate specificities of protein phosphatases-IIA and -IIB were identical. These findings, taken with the observation that phosphorylase phosphatase, beta-phosphorylase kinase phosphatase, glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities co-purified up to the Sephadex G-200 step, suggest that a single protein phosphatase (protein phosphatase-III) catalyses each of the dephosphorylation reactions that inhibit glycogenolysis or stimulate glycogen synthesis. This contention is further supported by results presented in the following paper [Cohen, P., Nimmo, G.A. & Antoniw, J.F. (1977) Biochem. J. 1628 435-444] which describes a heat-stable protein that is a specific inhibitor of protein phosphatase-III.", "contents": "Comparison of the substrate specificities of protein phosphatases involved in the regulation of glycogen metabolism in rabbit skeletal muscle. Muscle extracts were subjected to fractionation with ethanol, chromatography on DEAE-cellulose, precipitation with (NH4)2SO4 and gel filtration on Sephadex G-200. These fractions were assayed for protein phosphatase activities by using the following seven phosphoprotein substrates: phosphorylase a, glycogen synthase b1, glycogen synthase b2, phosphorylase kinase (phosphorylated in either the alpha-subunit or the beta-subunit), histone H1 and histone H2B. Three protein phosphatases with distinctive specificities were resolved by the final gel-filtration step and were termed I, II and III. Protein phosphatase-I, apparent mol.wt. 300000, was an active histone phosphatase, but it accounted for only 10-15% of the glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities and 2-3% of the phosphorylase kinase phosphatase and phosphorylase phosphatase activity recovered from the Sephadex G-200 column. Protein phosphatase-II, apparent mol.wt. 170000, possessed histone phosphatase activity similar to that of protein phosphatase-I. It possessed more than 95% of the activity towards the alpha-subunit of phosphorylase kinase that was recovered from Sephadex G-200. It accounted for 10-15% of the glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activity, but less than 5% of the activity against the beta-subunit of phosphorylase kinase and 1-2% of the phosphorylase phosphatase activity recovered from Sephadex G-200. Protein phosphatase-III was the most active histone phosphatase. It possessed 95% of the phosphorylase phosphatase and beta-phosphorylase kinase phosphatase activities, and 75% of the glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities recovered from Sephadex G-200. It accounted for less than 5% of the alpha-phosphorylase kinase phosphatase activity. Protein phosphatase-III was sometimes eluted from Sephadex-G-200 as a species of apparent mol.wt. 75000(termed IIIA), sometimes as a species of mol.wt. 46000(termed IIIB) and sometimes as a mixture of both components. The substrate specificities of protein phosphatases-IIA and -IIB were identical. These findings, taken with the observation that phosphorylase phosphatase, beta-phosphorylase kinase phosphatase, glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities co-purified up to the Sephadex G-200 step, suggest that a single protein phosphatase (protein phosphatase-III) catalyses each of the dephosphorylation reactions that inhibit glycogenolysis or stimulate glycogen synthesis. This contention is further supported by results presented in the following paper [Cohen, P., Nimmo, G.A. & Antoniw, J.F. (1977) Biochem. J. 1628 435-444] which describes a heat-stable protein that is a specific inhibitor of protein phosphatase-III."}
{"id": "PMID:192225", "title": "Specificity of a protein phosphatase inhibitor from rabbit skeletal muscle.", "content": "A hear-stable protein, which is a specific inhibitor of protein phosphatase-III, was purified 700-fold from skeletal muscle by a procedure that involved heat-treatment at 95 degrees C, chromatography on DEAE-cellulose and gel filtration on Sephadex G-100. The final step completely resolved the protein phosphatase inhibitor from the protein inhibitor of cyclic AMP-dependent protein kinase. The phosphorylase phosphatase, beta-phosphorylase kinase phosphatase, glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities of protein phosphatase-III [Antoniw, J. F., Nimmo, H. G., Yeaman, S. J. & Cohen, P.(1977) Biochem.J. 162, 423-433] were inhibited in a very similar manner by the protein phosphatase inhibitor and at least 95% inhibition was observed at high concentrations of inhibitor. The two forms of protein phosphatase-III, termed IIIA and IIIB, were equally susceptible to the protein phosphatase inhibitor. The protein phosphatase inhibitor was at least 200 times less effective in inhibiting the activity of protein phosphatase-I and protein phosphatase-II. The high degree of specificity of the inhibitor for protein phosphatase-III was used to show that 90% of the phosphorylase phosphatase and glycogen synthase phosphatase activities measured in muscle extracts are catalysed by protein phosphatase-III. Protein phosphatase-III was tightly associated with the protein-glycogen complex that can be isolated from skeletal muscle, whereas the protein phosphatase inhibitor and protein phosphatase-II were not. The results provide further evidence that the enzyme that catalyses the dephosphorylation of the alpha-subunit of phosphorylase kinase (protein phosphatase-II) and the enzyme that catalyses the dephosphorylation of the beta-subunit of phosphorylase kinase (protein phosphatase-III) are distinct. The results suggest that the protein phosphatase inhibitor may be a useful probe for differentiating different classes of protein phosphatases in mammalian cells.", "contents": "Specificity of a protein phosphatase inhibitor from rabbit skeletal muscle. A hear-stable protein, which is a specific inhibitor of protein phosphatase-III, was purified 700-fold from skeletal muscle by a procedure that involved heat-treatment at 95 degrees C, chromatography on DEAE-cellulose and gel filtration on Sephadex G-100. The final step completely resolved the protein phosphatase inhibitor from the protein inhibitor of cyclic AMP-dependent protein kinase. The phosphorylase phosphatase, beta-phosphorylase kinase phosphatase, glycogen synthase phosphatase-1 and glycogen synthase phosphatase-2 activities of protein phosphatase-III [Antoniw, J. F., Nimmo, H. G., Yeaman, S. J. & Cohen, P.(1977) Biochem.J. 162, 423-433] were inhibited in a very similar manner by the protein phosphatase inhibitor and at least 95% inhibition was observed at high concentrations of inhibitor. The two forms of protein phosphatase-III, termed IIIA and IIIB, were equally susceptible to the protein phosphatase inhibitor. The protein phosphatase inhibitor was at least 200 times less effective in inhibiting the activity of protein phosphatase-I and protein phosphatase-II. The high degree of specificity of the inhibitor for protein phosphatase-III was used to show that 90% of the phosphorylase phosphatase and glycogen synthase phosphatase activities measured in muscle extracts are catalysed by protein phosphatase-III. Protein phosphatase-III was tightly associated with the protein-glycogen complex that can be isolated from skeletal muscle, whereas the protein phosphatase inhibitor and protein phosphatase-II were not. The results provide further evidence that the enzyme that catalyses the dephosphorylation of the alpha-subunit of phosphorylase kinase (protein phosphatase-II) and the enzyme that catalyses the dephosphorylation of the beta-subunit of phosphorylase kinase (protein phosphatase-III) are distinct. The results suggest that the protein phosphatase inhibitor may be a useful probe for differentiating different classes of protein phosphatases in mammalian cells."}
{"id": "PMID:192226", "title": "Co-ordinate changes in enzymes of fatty acid synthesis, activation and esterification in rabbit mammary gland druing pregnancy and lactation.", "content": "1. The activities of fatty acid synthetase, acyl-CoA synthetase, glycerol phosphate acyltransferase and phosphatidate phosphatase were measured in the mammary glands of rabbits from day 16 of pregnancy to day 15 of post partum. 2. There were significant correlations between the increases in activities of these enzymes during this period. This was the case whether the activities were expressed per mg of homogenate protein, per g wet wt. of tissue or per total wet weight of the whole glands. The only exception was the lack of correlation between the activities of fatty acid synthetase and of phosphatidate phosphatase per g wet wt. of tissue. 3. These co-ordinate increases are discussed in relation to the changes which occur in fatty acid metabolism in the mammary gland during pregnancy and lactation.", "contents": "Co-ordinate changes in enzymes of fatty acid synthesis, activation and esterification in rabbit mammary gland druing pregnancy and lactation. 1. The activities of fatty acid synthetase, acyl-CoA synthetase, glycerol phosphate acyltransferase and phosphatidate phosphatase were measured in the mammary glands of rabbits from day 16 of pregnancy to day 15 of post partum. 2. There were significant correlations between the increases in activities of these enzymes during this period. This was the case whether the activities were expressed per mg of homogenate protein, per g wet wt. of tissue or per total wet weight of the whole glands. The only exception was the lack of correlation between the activities of fatty acid synthetase and of phosphatidate phosphatase per g wet wt. of tissue. 3. These co-ordinate increases are discussed in relation to the changes which occur in fatty acid metabolism in the mammary gland during pregnancy and lactation."}
{"id": "PMID:192248", "title": "Behavior of blood acetaldehyde in alcohol-treated rats following administration of thiurams.", "content": "Single moderate doses of Na-dimethyldithiocarbamate and Na-diethyldithiocarbamate (thiocarb), respectively, did not influence the rate of elimination of ethanol i.p. in female rats, but there was a concurrent substantial increase in the blood acetaldehyde content. Tetramethylthiuram disulfide (thiram) produced a slight decrease in the rate of elimination of ethanol, while a comparable dose of tetramethylthiuram disulfide (disulfiram) failed to affect ethanol disappearance. At the same time, the blood acetaldehyde concentration showed a considerable increase which after thiram was much more significant than after disulfiram, Identical thiuram doses caused a significant reduction in the rate of elimination of acetaldehyde i.v., which suggests an inhibition of the aldehyde dehydrogenasel aldehyde oxidase and helps to explain the elevated blood acetaldehyde concentration which was observed in the presence of ethanol. It is concluded from these findings that thiuram activity decreases as the number of carbon atoms at the side-chains of the molecule is increasing.", "contents": "Behavior of blood acetaldehyde in alcohol-treated rats following administration of thiurams. Single moderate doses of Na-dimethyldithiocarbamate and Na-diethyldithiocarbamate (thiocarb), respectively, did not influence the rate of elimination of ethanol i.p. in female rats, but there was a concurrent substantial increase in the blood acetaldehyde content. Tetramethylthiuram disulfide (thiram) produced a slight decrease in the rate of elimination of ethanol, while a comparable dose of tetramethylthiuram disulfide (disulfiram) failed to affect ethanol disappearance. At the same time, the blood acetaldehyde concentration showed a considerable increase which after thiram was much more significant than after disulfiram, Identical thiuram doses caused a significant reduction in the rate of elimination of acetaldehyde i.v., which suggests an inhibition of the aldehyde dehydrogenasel aldehyde oxidase and helps to explain the elevated blood acetaldehyde concentration which was observed in the presence of ethanol. It is concluded from these findings that thiuram activity decreases as the number of carbon atoms at the side-chains of the molecule is increasing."}
{"id": "PMID:192249", "title": "[The protecting action of a combination of vasoactivating substances (CRP) on disturbances of the cerebral blood flow and metabolism and the cortical electrical activity (author's transl)].", "content": "The effect of anoxia and direct cortical stimulation was investigated in control, hypotensive and post reinfusional periods, before and after treatment with a combination of coumarin/rutin sulphate sodium salts/proxyphylline (CRP, Theokal). Theokal lowered the mean arterial pressure and a slight NADH oxidation appeared. Blood flow did not change after Theokal in spite of the 30 mm Hg blood pressure drop. This suggests an improved oxygen supply to the cortical cells. The increase in anoxic NADH reaction and the faster reoxidation kinetics of NADH following anoxia provided further evidence for the beneficial effect of Theokal on brain circulation and metabolism. It is to be emphasized that the described action of the drug can be observed only in hemorrhagic shock but not in normal animals.", "contents": "[The protecting action of a combination of vasoactivating substances (CRP) on disturbances of the cerebral blood flow and metabolism and the cortical electrical activity (author's transl)]. The effect of anoxia and direct cortical stimulation was investigated in control, hypotensive and post reinfusional periods, before and after treatment with a combination of coumarin/rutin sulphate sodium salts/proxyphylline (CRP, Theokal). Theokal lowered the mean arterial pressure and a slight NADH oxidation appeared. Blood flow did not change after Theokal in spite of the 30 mm Hg blood pressure drop. This suggests an improved oxygen supply to the cortical cells. The increase in anoxic NADH reaction and the faster reoxidation kinetics of NADH following anoxia provided further evidence for the beneficial effect of Theokal on brain circulation and metabolism. It is to be emphasized that the described action of the drug can be observed only in hemorrhagic shock but not in normal animals."}
{"id": "PMID:192250", "title": "[Human papilloma viruses (author's transl)].", "content": "Various types of human papillomas (warts) can be differentiated according to clinical parameters: Verrucae vulgares, plantares, planae and seborrheicae, in addition genital warts (Condylomata acuminata) and laryngeal papillomas. With the exception of Verrucae vulgares and plantares the epidemiology of these types of warts displays significantly different patterns. It was possible to demonstrate the heterogeneity of human wart viruses also by biochemical and serological means: we have identified 4 different types of human papilloma viruses so far, 3 of which are closely related with each other. Their potential role in the induction of malignant tumors in man is discussed.", "contents": "[Human papilloma viruses (author's transl)]. Various types of human papillomas (warts) can be differentiated according to clinical parameters: Verrucae vulgares, plantares, planae and seborrheicae, in addition genital warts (Condylomata acuminata) and laryngeal papillomas. With the exception of Verrucae vulgares and plantares the epidemiology of these types of warts displays significantly different patterns. It was possible to demonstrate the heterogeneity of human wart viruses also by biochemical and serological means: we have identified 4 different types of human papilloma viruses so far, 3 of which are closely related with each other. Their potential role in the induction of malignant tumors in man is discussed."}
{"id": "PMID:192251", "title": "Possible utilization of extracorporeal hemoperfusion in the treatment of coronary artery disease. A hypothesis and proposal for animal studies.", "content": "It is proposed that in vivo immunoadsorption may be utilized in the treatment of coronary artery disease. The proposed method is based on binding of low density lipoproteins and cholesterol to antibodies directed against low density lipoproteins which are bound to a matrix in an extracorporeal hemoperfusion column. The various observations that suggest the hypothesis are presented. The feasibility of the proposed method and some of the problems that may be encountered in its utilization are discussed. The method should be evaluated in animal studies prior to consideration of clinical trials in patients.", "contents": "Possible utilization of extracorporeal hemoperfusion in the treatment of coronary artery disease. A hypothesis and proposal for animal studies. It is proposed that in vivo immunoadsorption may be utilized in the treatment of coronary artery disease. The proposed method is based on binding of low density lipoproteins and cholesterol to antibodies directed against low density lipoproteins which are bound to a matrix in an extracorporeal hemoperfusion column. The various observations that suggest the hypothesis are presented. The feasibility of the proposed method and some of the problems that may be encountered in its utilization are discussed. The method should be evaluated in animal studies prior to consideration of clinical trials in patients."}
{"id": "PMID:192252", "title": "Effect of essential oil of onion and garlic on experimental atherosclerosis in rabbits.", "content": "The effects of the essential oils of onion (extracted from 2 g of raw onion per kg body weight) and garlic (extracted from 1 g of raw garlic per kg body weight) have been observed on experimental atherosclerosis produced by cholesterol feeding (0.5 g/kg) in rabbits. The rise in serum cholesterol and serum triglycerides was significantly reduced by both onion and garlic during the 4-month period of study. Cholesterol feeding significantly increased beta-(P less than 0.01) and pre-beta (P less than 0.001) lipoproteins while decreasing the alpha-fraction (P less than 0.001). Onion and garlic both prevented these changes. The beta/alpha ratio, which was initially 1.6 : 1, rose to 4.5 : 1 and 5.7 : 1 at the end of 2 months and 4 months of cholesterol feeding. However, this ratio did not increase significantly, both at the 2-month and 4-month period, when onion and garlic were added. Fibrinolytic activity significantly increased with onion (P less than 0.001) and garlic (P less than 0.001) while feeding only cholesterol actually decreased it (P less than 0.001). Onion and garlic reducec aortic atheroma by about half. It is suggested that the essential oils of onion and garlic protect against experimental atherosclerosis by preventing the fall in the alpha lipoprotein fraction and by enhancing fibrinolytic activity, as well as by lowering the serum cholesterol and triglyceride levels.", "contents": "Effect of essential oil of onion and garlic on experimental atherosclerosis in rabbits. The effects of the essential oils of onion (extracted from 2 g of raw onion per kg body weight) and garlic (extracted from 1 g of raw garlic per kg body weight) have been observed on experimental atherosclerosis produced by cholesterol feeding (0.5 g/kg) in rabbits. The rise in serum cholesterol and serum triglycerides was significantly reduced by both onion and garlic during the 4-month period of study. Cholesterol feeding significantly increased beta-(P less than 0.01) and pre-beta (P less than 0.001) lipoproteins while decreasing the alpha-fraction (P less than 0.001). Onion and garlic both prevented these changes. The beta/alpha ratio, which was initially 1.6 : 1, rose to 4.5 : 1 and 5.7 : 1 at the end of 2 months and 4 months of cholesterol feeding. However, this ratio did not increase significantly, both at the 2-month and 4-month period, when onion and garlic were added. Fibrinolytic activity significantly increased with onion (P less than 0.001) and garlic (P less than 0.001) while feeding only cholesterol actually decreased it (P less than 0.001). Onion and garlic reducec aortic atheroma by about half. It is suggested that the essential oils of onion and garlic protect against experimental atherosclerosis by preventing the fall in the alpha lipoprotein fraction and by enhancing fibrinolytic activity, as well as by lowering the serum cholesterol and triglyceride levels."}
{"id": "PMID:192257", "title": "The intermediate coronary care unit. A stage in continued coronary care.", "content": "The concept of continued and progressive coronary care rather than intermediate coronary care is proposed. At each clinical stage the patient may be at risk and his management needs to be planned appropriately--prevention of the development of coronary disease, prehospital care, acute coronary care, subacute coronary care, and late hospital stay. Meticulous continued care once the patient leaves the hospital and returns home may be needed for a long time. Although the benefit of an intermediate coronary care unit has not yet been proved, significant patient risk continues beyond 12 days of hospital admission. High risk patient subsets are emerging requiring careful continued monitoring and the ability to undertake emergency measures as needed, and this is particularly so in patients suffering large anterior infarction, in those with infarction associated with cardiac failure, when infarction is associated with fascicular block and other types of conduction disturbances, and in patients who continue with rhythm disturbances after their admission to the hospital. Electrocardiograph leads III and VI displayed simultaneously should be routinely monitored in patients with fascicular blocks and acute anterior infarction as a guide to instituting prophylactic transvenous pacemaking. The continuation of intensive patient care and monitoring beyond the usual 2 to 5 days in a coronary care unit allows early mobilisation of patients in safety, thus speeding their ultimate rehabilitation. There is, as yet, no satisfactory study documenting the need for intermediate coronary care units, but much presumptive evidence is available to indicate that this is so. A carefully controlled randomised study would be invaluable.", "contents": "The intermediate coronary care unit. A stage in continued coronary care. The concept of continued and progressive coronary care rather than intermediate coronary care is proposed. At each clinical stage the patient may be at risk and his management needs to be planned appropriately--prevention of the development of coronary disease, prehospital care, acute coronary care, subacute coronary care, and late hospital stay. Meticulous continued care once the patient leaves the hospital and returns home may be needed for a long time. Although the benefit of an intermediate coronary care unit has not yet been proved, significant patient risk continues beyond 12 days of hospital admission. High risk patient subsets are emerging requiring careful continued monitoring and the ability to undertake emergency measures as needed, and this is particularly so in patients suffering large anterior infarction, in those with infarction associated with cardiac failure, when infarction is associated with fascicular block and other types of conduction disturbances, and in patients who continue with rhythm disturbances after their admission to the hospital. Electrocardiograph leads III and VI displayed simultaneously should be routinely monitored in patients with fascicular blocks and acute anterior infarction as a guide to instituting prophylactic transvenous pacemaking. The continuation of intensive patient care and monitoring beyond the usual 2 to 5 days in a coronary care unit allows early mobilisation of patients in safety, thus speeding their ultimate rehabilitation. There is, as yet, no satisfactory study documenting the need for intermediate coronary care units, but much presumptive evidence is available to indicate that this is so. A carefully controlled randomised study would be invaluable."}
{"id": "PMID:192258", "title": "The actions of cyclic AMP, its butyryl derivatives and Na butyrate on the proliferation of malignant trophoblast cells in vitro.", "content": "Cyclic AMP, and its derivatives N6-monobutyryl cyclic AMP and dibutyryl cyclic AMP, have been found to inhibit the proliferation of trophoblast cells of the BeWo cell line in vitro. Sodium butyrate (1 mM), a possible degradation product of the butyrate derivatives, also inhibited cell proliferation, giving similar growth rates to equimolar dibutyryl cyclic AMP. The inhibition by butyrate was however, not sufficient to account for the action of 1 mM N6-monobutyryl cycli AMP, which, like cyclic AMP, completely inhibited cell proliferation. The potency, specificity and toxicity of the substances were compared. The results suggest different modes of action for cyclic AMP and dibutyryl cyclic AMP.", "contents": "The actions of cyclic AMP, its butyryl derivatives and Na butyrate on the proliferation of malignant trophoblast cells in vitro. Cyclic AMP, and its derivatives N6-monobutyryl cyclic AMP and dibutyryl cyclic AMP, have been found to inhibit the proliferation of trophoblast cells of the BeWo cell line in vitro. Sodium butyrate (1 mM), a possible degradation product of the butyrate derivatives, also inhibited cell proliferation, giving similar growth rates to equimolar dibutyryl cyclic AMP. The inhibition by butyrate was however, not sufficient to account for the action of 1 mM N6-monobutyryl cycli AMP, which, like cyclic AMP, completely inhibited cell proliferation. The potency, specificity and toxicity of the substances were compared. The results suggest different modes of action for cyclic AMP and dibutyryl cyclic AMP."}
{"id": "PMID:192259", "title": "Immunogenicity of tumour cells modified with various chemicals.", "content": "Mouse tumour cells were treated with various chemical modifiers. The number of modifying groups per cell was determined with labelled reagents. The effects of the different modifying groups on the immunogenicity of the tumour cells was tested in syngeneic mice for tumour protection using a challenge dose of viable cells at 1000 or 10,000 time LD100. Best protection was obtained after immunization of animals with tumour cells modified with dimethylsulphate or acetic anhydride, or with glutardialdehyde-fixed cells treated with a carbodiimide and methylamine. Up to 40% of the animals remained tumour-free. The other animals exhibited a greatly increased mean survival time. The post-challenge sera showed no detectable amounts of antibodies against the tumour cells.", "contents": "Immunogenicity of tumour cells modified with various chemicals. Mouse tumour cells were treated with various chemical modifiers. The number of modifying groups per cell was determined with labelled reagents. The effects of the different modifying groups on the immunogenicity of the tumour cells was tested in syngeneic mice for tumour protection using a challenge dose of viable cells at 1000 or 10,000 time LD100. Best protection was obtained after immunization of animals with tumour cells modified with dimethylsulphate or acetic anhydride, or with glutardialdehyde-fixed cells treated with a carbodiimide and methylamine. Up to 40% of the animals remained tumour-free. The other animals exhibited a greatly increased mean survival time. The post-challenge sera showed no detectable amounts of antibodies against the tumour cells."}
{"id": "PMID:192260", "title": "Cold lymphocytotoxic antibodies in nasopharyngeal carcinoma.", "content": "Sera from patients with nasopharyngeal carcinoma (NPC), a disease associated with Epstein-Barr virus (EBV), were found to be cytotoxic at 15% degrees C in the presence of complement for a panel of human lymphocytes, with a higher frequency than those of matched controls. The cold lymphocytotoxic antibodies (LTA) responsible for this activity have the same properties as those described in sera from individuals with acute viral infections. The frequency and geometric mean titres (GMT) of LTA varied with the origin of the patient (Chinese larger than North African larger than Caucasian) and the stage of the disease (Stage IV larger than Stage I). A positive correlation between LTA and anti-EBV titres was found with regard to antibodies to the viral capsid antigen (VCA) and the EBV-specified nuclear antigen (EBNA). The absence of correlation between LTA and anti-early antigen (EA) titres probable reflects the complex relationships existing between viral infection and LTA production, but is compatible with the hypothesis that LTA acts as an immune regulatory mechanism in viral infections.", "contents": "Cold lymphocytotoxic antibodies in nasopharyngeal carcinoma. Sera from patients with nasopharyngeal carcinoma (NPC), a disease associated with Epstein-Barr virus (EBV), were found to be cytotoxic at 15% degrees C in the presence of complement for a panel of human lymphocytes, with a higher frequency than those of matched controls. The cold lymphocytotoxic antibodies (LTA) responsible for this activity have the same properties as those described in sera from individuals with acute viral infections. The frequency and geometric mean titres (GMT) of LTA varied with the origin of the patient (Chinese larger than North African larger than Caucasian) and the stage of the disease (Stage IV larger than Stage I). A positive correlation between LTA and anti-EBV titres was found with regard to antibodies to the viral capsid antigen (VCA) and the EBV-specified nuclear antigen (EBNA). The absence of correlation between LTA and anti-early antigen (EA) titres probable reflects the complex relationships existing between viral infection and LTA production, but is compatible with the hypothesis that LTA acts as an immune regulatory mechanism in viral infections."}
{"id": "PMID:192261", "title": "Effects of theophylline and dibutyryl cyclic AMP on proliferation and keratinization of human keratinocytes.", "content": "Recent evidence suggested that cyclic adenosine 3',5'-monophosphate (cAMP) may be involved in the regulation of cell proliferation and differentiation. The effects of theophylline and dibutyryl cAMP on cell division and keratinization of human epidermal cultures were examined. Nine  to 12-day-old cultures were treated with these agents, separately and in combination, for various intervals. Both agents, either singly or in combination, depressed mitoses. The maximum mitotic inhibition was obtained in cultures treated with theophylline or theophylline plus dibutyryl cAMP. Tritiated thymidine studies showed that the test agents had no effect on labelling index (LI) at 4 h, but a 74% inhibition of LI was observed at 24 h. The maximum inhibition of LI (93%) occurred at 96 hours. In contrast to the control cultures, which rarely contain keratohyaline granules (KG), a marked increase in the production of these granules occurred in cultures treated with dibutyryl cAMP plus theophylline. The KG were present over the whole outgrowth. Theophylline alone also stimulated the production of KG, whereas dibutyryl cAMP had no effect. These data show that these agents inhibit cell division and this inhibition may be accompanied by an increased production of KG.", "contents": "Effects of theophylline and dibutyryl cyclic AMP on proliferation and keratinization of human keratinocytes. Recent evidence suggested that cyclic adenosine 3',5'-monophosphate (cAMP) may be involved in the regulation of cell proliferation and differentiation. The effects of theophylline and dibutyryl cAMP on cell division and keratinization of human epidermal cultures were examined. Nine  to 12-day-old cultures were treated with these agents, separately and in combination, for various intervals. Both agents, either singly or in combination, depressed mitoses. The maximum mitotic inhibition was obtained in cultures treated with theophylline or theophylline plus dibutyryl cAMP. Tritiated thymidine studies showed that the test agents had no effect on labelling index (LI) at 4 h, but a 74% inhibition of LI was observed at 24 h. The maximum inhibition of LI (93%) occurred at 96 hours. In contrast to the control cultures, which rarely contain keratohyaline granules (KG), a marked increase in the production of these granules occurred in cultures treated with dibutyryl cAMP plus theophylline. The KG were present over the whole outgrowth. Theophylline alone also stimulated the production of KG, whereas dibutyryl cAMP had no effect. These data show that these agents inhibit cell division and this inhibition may be accompanied by an increased production of KG."}
{"id": "PMID:192262", "title": "Hypertrichosis lanuginosa acquisita associated with pancreatic carcinoma.", "content": "A patient with hypertrichosis lanuginosa acquisita associated with pancreatic islet cell carcinoma, probably D cell type, is presented. The hypertrichosis antedated other evidence of malignancy.", "contents": "Hypertrichosis lanuginosa acquisita associated with pancreatic carcinoma. A patient with hypertrichosis lanuginosa acquisita associated with pancreatic islet cell carcinoma, probably D cell type, is presented. The hypertrichosis antedated other evidence of malignancy."}
{"id": "PMID:192263", "title": "Studies of the influence of cyclic nucleotides on in vitro haemoglobin synthesis.", "content": "The influence of various cyclic nucleotides on in vitro haemoglobin synthesis has been examined in suspension cultures of mammalian marrow cells. Over a wide range of concentrations, dibutyryl cyclic AMP (db-cAMP) was either ineffective or inhibited haemoglobin synthesis by marrow cells from rat, mouse and guinea-pig. However, 10(-3) M db-cAMP consistently stimulated haemoglobin synthesis in cultures of human, sheep, rabbit and canine cells, with the latter being most responsive. This effect, which approached in magnitude that of erythropoietin (ESF) itself, was specific for cAMP and its mono- and dibutyryl derivatives and was not inhibited by anti-ESF. Adenosine, AMP, ADP, ATP, cGMP, db-cGMP, cCMP, cIMP and sodium butyrate were either inactive or inhibitory at similar concentrations. Enhancement of haemoglobin synthesis was also observed with the phosphodiesterase inhibitor, RO-20-1724. The susceptibility to ionizing radiation of the response to ESF and db-cAMP was marked, indicating that the increased haemoglobin synthesis in this system was proliferation dependent, although the response to db-cAMP was less radiosensitive. Studies with tritiated thymidine showed that about 50% of the cells which were responding to either db-cAMP or ESF were actively engaged in DNA synthesis. However, the physical characteristics of db-cAMP-and ESF-responsive cells were dissimilar as analysed by their velocity sedimentation properties. These studies demonstrate that cAMP has a major stimulatory effect on haemoglobin synthesis with cells from selected mammalian species with activity approaching that of ESF, but the target cells most responsive to these agents appear different. The results suggest that cyclic nucleotide-related mechanisms may modulate in vitro erythropoiesis.", "contents": "Studies of the influence of cyclic nucleotides on in vitro haemoglobin synthesis. The influence of various cyclic nucleotides on in vitro haemoglobin synthesis has been examined in suspension cultures of mammalian marrow cells. Over a wide range of concentrations, dibutyryl cyclic AMP (db-cAMP) was either ineffective or inhibited haemoglobin synthesis by marrow cells from rat, mouse and guinea-pig. However, 10(-3) M db-cAMP consistently stimulated haemoglobin synthesis in cultures of human, sheep, rabbit and canine cells, with the latter being most responsive. This effect, which approached in magnitude that of erythropoietin (ESF) itself, was specific for cAMP and its mono- and dibutyryl derivatives and was not inhibited by anti-ESF. Adenosine, AMP, ADP, ATP, cGMP, db-cGMP, cCMP, cIMP and sodium butyrate were either inactive or inhibitory at similar concentrations. Enhancement of haemoglobin synthesis was also observed with the phosphodiesterase inhibitor, RO-20-1724. The susceptibility to ionizing radiation of the response to ESF and db-cAMP was marked, indicating that the increased haemoglobin synthesis in this system was proliferation dependent, although the response to db-cAMP was less radiosensitive. Studies with tritiated thymidine showed that about 50% of the cells which were responding to either db-cAMP or ESF were actively engaged in DNA synthesis. However, the physical characteristics of db-cAMP-and ESF-responsive cells were dissimilar as analysed by their velocity sedimentation properties. These studies demonstrate that cAMP has a major stimulatory effect on haemoglobin synthesis with cells from selected mammalian species with activity approaching that of ESF, but the target cells most responsive to these agents appear different. The results suggest that cyclic nucleotide-related mechanisms may modulate in vitro erythropoiesis."}
{"id": "PMID:192264", "title": "Effect of protein deficiency on absorption, transport and distribution of alpha-tocopherol in the rat.", "content": "The absorption, transport and distribution of alpha-[3H]tocopherol were greatly decreased in protein deficiency. This was reflected in the subcellular distribution of alpha-[3H]tocopherol in livers of protein-deficient rats. The ratio, bound:free for alpha-[3H]tocopherol, also decreased in both serum and liver cytosol. After protein refeeding, absorption, transport and distribution patterns of alpha-[3H]tocopherol for the protein-deficient rats were restored to patterns similar to those of control animals.", "contents": "Effect of protein deficiency on absorption, transport and distribution of alpha-tocopherol in the rat. The absorption, transport and distribution of alpha-[3H]tocopherol were greatly decreased in protein deficiency. This was reflected in the subcellular distribution of alpha-[3H]tocopherol in livers of protein-deficient rats. The ratio, bound:free for alpha-[3H]tocopherol, also decreased in both serum and liver cytosol. After protein refeeding, absorption, transport and distribution patterns of alpha-[3H]tocopherol for the protein-deficient rats were restored to patterns similar to those of control animals."}
{"id": "PMID:192265", "title": "Interaction of substrates and inhibitors with the homoserine dehydrogenase of kinase-inactivated aspartokinase I.", "content": "The aspartokinase activity of the aspartokinase-homoserine dehydrogenase complex of Escherichia coli was affinity labeled with substrates ATP, aspartate, and feedback inhibitor threonine. Exchange-inert ternary adducts of Co(III)-aspartokinase and either ATP, aspartate or threonine were formed by oxidation of corresponding Co(II) ternary complexes with H2O2. The ternary enzyme-Co(III)-threonine adduct (I) had 3.8 threonine binding sites per tetramer, one-half that of the native enzyme. The binding of threonine to I was still cooperative as determined by equilibrium dialysis (nH = 2.2) or by studying inhibition of residual dehydrogenase activity (nH = 2.7). Threonine still protected the SH groups of I against 5,5'-dithiobis(2-nitrobenzoate) (DTNB) reaction but the number of SH groups reacting with thiol reagents (DTNB) was reduced by 1-2 per subunit in the absence of threonine. This suggests either that Co(III) is bound to the enzyme via sulfhydryl groups or that 1-2SH groups are buried or rendered inaccessible in I. The binding of threonine to sites not blocked by the affinity labeling produced changes in the circular dichroism of the complex comparable to changes produced by threonine binding to native enzyme and also protected against proteolytic digestion. The major conformational changes produced by threonine are thus ascribable to binding at this one class of regulatory sites. The interactions of kinase substrates with various aspartokinase-Co(III) complexes containing ATP, aspartate, or threonine and a threonine-insensitive homoserine dehydrogenase produced by mild proteolysis were studied. The inhibition of homoserine dehydrogenase by kinase substrates is not due to binding of these inhibitors at the kinase active site but was shown to be due to binding to sites within the dehydrogenase domain of the enzyme. L-alpha-Aminobutyrate, a presumed threonine analogue, also inhibits the dehydrogenase by binding at the same or similar sites in the dehydrogenase domain and not at threonine regulatory site.", "contents": "Interaction of substrates and inhibitors with the homoserine dehydrogenase of kinase-inactivated aspartokinase I. The aspartokinase activity of the aspartokinase-homoserine dehydrogenase complex of Escherichia coli was affinity labeled with substrates ATP, aspartate, and feedback inhibitor threonine. Exchange-inert ternary adducts of Co(III)-aspartokinase and either ATP, aspartate or threonine were formed by oxidation of corresponding Co(II) ternary complexes with H2O2. The ternary enzyme-Co(III)-threonine adduct (I) had 3.8 threonine binding sites per tetramer, one-half that of the native enzyme. The binding of threonine to I was still cooperative as determined by equilibrium dialysis (nH = 2.2) or by studying inhibition of residual dehydrogenase activity (nH = 2.7). Threonine still protected the SH groups of I against 5,5'-dithiobis(2-nitrobenzoate) (DTNB) reaction but the number of SH groups reacting with thiol reagents (DTNB) was reduced by 1-2 per subunit in the absence of threonine. This suggests either that Co(III) is bound to the enzyme via sulfhydryl groups or that 1-2SH groups are buried or rendered inaccessible in I. The binding of threonine to sites not blocked by the affinity labeling produced changes in the circular dichroism of the complex comparable to changes produced by threonine binding to native enzyme and also protected against proteolytic digestion. The major conformational changes produced by threonine are thus ascribable to binding at this one class of regulatory sites. The interactions of kinase substrates with various aspartokinase-Co(III) complexes containing ATP, aspartate, or threonine and a threonine-insensitive homoserine dehydrogenase produced by mild proteolysis were studied. The inhibition of homoserine dehydrogenase by kinase substrates is not due to binding of these inhibitors at the kinase active site but was shown to be due to binding to sites within the dehydrogenase domain of the enzyme. L-alpha-Aminobutyrate, a presumed threonine analogue, also inhibits the dehydrogenase by binding at the same or similar sites in the dehydrogenase domain and not at threonine regulatory site."}
{"id": "PMID:192266", "title": "Fluorescence energy transfer between heterologous active sites of affinity-labeled aspartokinase of Escherichia coli.", "content": "The distance between aspartokinase and homoserine dehydrogenase active sites was determined using fluorescence energy transfer between modified substrates. The fluorescent 1,N(6)-ethenoadenosine 5'-triphosphate was bound at the kinase active site by Co(III) affinity labeling. Reduced thionicotinamide adenine dinucleotide phosphate quenched the fluorescence of bound nucleotide. Fluorescence depolarization measurements led to a delimitation of the value of the dipolar orientation factor to the range 0.3 to 2.8. The distance between the fluorescent probe and the quencher was 29 +/- 4 A. In the presence of threonine, this distance increased to 36 +/- 5 A. Threonine binding either increased the intersite distance by ca. 7 A or caused a reorientation of the probe at the dehydrogenase site.", "contents": "Fluorescence energy transfer between heterologous active sites of affinity-labeled aspartokinase of Escherichia coli. The distance between aspartokinase and homoserine dehydrogenase active sites was determined using fluorescence energy transfer between modified substrates. The fluorescent 1,N(6)-ethenoadenosine 5'-triphosphate was bound at the kinase active site by Co(III) affinity labeling. Reduced thionicotinamide adenine dinucleotide phosphate quenched the fluorescence of bound nucleotide. Fluorescence depolarization measurements led to a delimitation of the value of the dipolar orientation factor to the range 0.3 to 2.8. The distance between the fluorescent probe and the quencher was 29 +/- 4 A. In the presence of threonine, this distance increased to 36 +/- 5 A. Threonine binding either increased the intersite distance by ca. 7 A or caused a reorientation of the probe at the dehydrogenase site."}
{"id": "PMID:192267", "title": "Role of tryptophan in the spectral and catalytic properties of the copper enzyme, galactose oxidase.", "content": "Previous results indicate that a tryptophan residue(s) may interact with the sugar substrate and Cu(II) atom of galactose oxidase (Ettinger, M. J., and Kosman, D. J. (1974), Biochemistry 13, 1248). We now show that N-bromosuccinimide (NBS) reduces enzymatic activity to 2% as two tryptophans are oxidized; only four residues are easily oxidized in the holoenzyme. An enzymatic activity vs. number of residues oxidized profile suggests that this inactivation is probably associated with only one of the first 2 residues oxidized. There is no evidence for chain cleavage or modification of amino acids other than tryptophan. While substrate protection is not afforded by the sugar substrate, the activity-related tryptophan is placed within the active-site locus by spectral evidence. NBS oxidation of two tryptophans results in a marked diminution of the large copper optical-activity transition at 314 nm. Under some reaction conditions, a doubling of ellipticity in the 600-nm region of copper CD is also observed. The effects of the NBS oxidation on the CD spectra of galactose oxidase permit the assignment of the 314-nm CD band to a charge-transfer transition and the 229-nm extremum to a specific tryptophan contribution. The AZZ parameter from electron spin resonance spectra is also markedly reduced by the NBS oxidation. Moreover, while cyanide binds to the native enzyme without reducing the Cu(II) atom, cyanide rapidly reduces the Cu(II) atom to Cu(I) in the NBS-oxidized enzyme. These CD and ESR results are taken to suggest that one aspect of the inactivation by NBS oxidation may be a conversion of the pseudosquare planar copper complex in the native enzyme to a more distorted, towards tetrahedral, complex in the inactivated enzyme. Since the inactivation can be accomplished without affecting binding of the sugar substrate, tryptophan oxidation must affect catalysis per se.", "contents": "Role of tryptophan in the spectral and catalytic properties of the copper enzyme, galactose oxidase. Previous results indicate that a tryptophan residue(s) may interact with the sugar substrate and Cu(II) atom of galactose oxidase (Ettinger, M. J., and Kosman, D. J. (1974), Biochemistry 13, 1248). We now show that N-bromosuccinimide (NBS) reduces enzymatic activity to 2% as two tryptophans are oxidized; only four residues are easily oxidized in the holoenzyme. An enzymatic activity vs. number of residues oxidized profile suggests that this inactivation is probably associated with only one of the first 2 residues oxidized. There is no evidence for chain cleavage or modification of amino acids other than tryptophan. While substrate protection is not afforded by the sugar substrate, the activity-related tryptophan is placed within the active-site locus by spectral evidence. NBS oxidation of two tryptophans results in a marked diminution of the large copper optical-activity transition at 314 nm. Under some reaction conditions, a doubling of ellipticity in the 600-nm region of copper CD is also observed. The effects of the NBS oxidation on the CD spectra of galactose oxidase permit the assignment of the 314-nm CD band to a charge-transfer transition and the 229-nm extremum to a specific tryptophan contribution. The AZZ parameter from electron spin resonance spectra is also markedly reduced by the NBS oxidation. Moreover, while cyanide binds to the native enzyme without reducing the Cu(II) atom, cyanide rapidly reduces the Cu(II) atom to Cu(I) in the NBS-oxidized enzyme. These CD and ESR results are taken to suggest that one aspect of the inactivation by NBS oxidation may be a conversion of the pseudosquare planar copper complex in the native enzyme to a more distorted, towards tetrahedral, complex in the inactivated enzyme. Since the inactivation can be accomplished without affecting binding of the sugar substrate, tryptophan oxidation must affect catalysis per se."}
{"id": "PMID:192268", "title": "Human skin collagenase: isolation of precursor and active forms from both fibroblast and organ cultures.", "content": "Human skin procollagenase has been isolated, in pure form, from the medium of fibroblasts cultured in the presence or absence of added serum. Purification was achieved using a combination of cation-exchange (phosphocellulose or carboxymethylcellulose) and gel-filtration chromatography. Two forms (60 000 and 55 000 daltons) of the procollagenase were detected by electrophoresis in sodium dodecyl sulfatepolyacrylamide gels and could be separated by chromatography on Ultrogel AcA-44. Each form was converted to active enzyme by trypsin, producing species of 50 000 and 45 000 daltons, respectively. An autoactivation process also occurred, which yielded active enzyme without a detectable change in molecular weight. Procollagenase also was found in organ cultures of human skin but only when serum was added to the medium. This suggests that a serum-inhibitable proteolytic system is present in these cultures which, like trypsin, converts procollagenase to the active enzyme forms that can be isolated from serum-free organ culture medium. The collagenase species obtained from either fibroblast or organ culture medium were chromatographically and electrophoretically identical.", "contents": "Human skin collagenase: isolation of precursor and active forms from both fibroblast and organ cultures. Human skin procollagenase has been isolated, in pure form, from the medium of fibroblasts cultured in the presence or absence of added serum. Purification was achieved using a combination of cation-exchange (phosphocellulose or carboxymethylcellulose) and gel-filtration chromatography. Two forms (60 000 and 55 000 daltons) of the procollagenase were detected by electrophoresis in sodium dodecyl sulfatepolyacrylamide gels and could be separated by chromatography on Ultrogel AcA-44. Each form was converted to active enzyme by trypsin, producing species of 50 000 and 45 000 daltons, respectively. An autoactivation process also occurred, which yielded active enzyme without a detectable change in molecular weight. Procollagenase also was found in organ cultures of human skin but only when serum was added to the medium. This suggests that a serum-inhibitable proteolytic system is present in these cultures which, like trypsin, converts procollagenase to the active enzyme forms that can be isolated from serum-free organ culture medium. The collagenase species obtained from either fibroblast or organ culture medium were chromatographically and electrophoretically identical."}
{"id": "PMID:192269", "title": "Hydroxylation of (Pro-Pro-Gly)5 and (Pro-Pro-Gly)10 by prolyl hydroxylase. Evidence for an asymmetric active site in the enzyme.", "content": "Previous studies with 14C-labeled synthetic peptides demonstrated that prolyl hydroxylase, which synthesizes the hydroxyproline in collagen, preferentially hydroxylates the fourth triplet from the NH-terminal end of the peptide (Pro-Pro-Gly)5. In the experiments reported here, the prolyl hydroxylase reaction was investigated further by preparing chemically modified derivatives of (Pro-Pro-Gly)5 and by synthesizing 14C-labeled preparations of (Pro-Pro-Gly)10. Essentially, the same kcat value was found for the hydroxylation of (Pro-Pro-Gly)5, N-acetyl-(Pro-Pro-Gly)5, (Pro-Pro-Gly)5 methyl ester, (Pro-Pro-Gly)10, and for larger polypeptide substrates of the enzyme. It appeared therefore that preferential hydroxylation of specific triplets in peptides of the structure (Pro-Pro-Gly)n cannot be explained by differences in the kinetic constants for individual triplets. Hydroxylation of 14C-labeled preparations of (Pro-Pro-Gly)10 demonstrated that the ninth triplet was preferentially hydroxylated over any other triplet. The results were best explained by the hypothesis that prolyl hydroxylase has an asymmetric active site in which binding subsites are located adjacent to but not symmetrical with the catalytic subsite.", "contents": "Hydroxylation of (Pro-Pro-Gly)5 and (Pro-Pro-Gly)10 by prolyl hydroxylase. Evidence for an asymmetric active site in the enzyme. Previous studies with 14C-labeled synthetic peptides demonstrated that prolyl hydroxylase, which synthesizes the hydroxyproline in collagen, preferentially hydroxylates the fourth triplet from the NH-terminal end of the peptide (Pro-Pro-Gly)5. In the experiments reported here, the prolyl hydroxylase reaction was investigated further by preparing chemically modified derivatives of (Pro-Pro-Gly)5 and by synthesizing 14C-labeled preparations of (Pro-Pro-Gly)10. Essentially, the same kcat value was found for the hydroxylation of (Pro-Pro-Gly)5, N-acetyl-(Pro-Pro-Gly)5, (Pro-Pro-Gly)5 methyl ester, (Pro-Pro-Gly)10, and for larger polypeptide substrates of the enzyme. It appeared therefore that preferential hydroxylation of specific triplets in peptides of the structure (Pro-Pro-Gly)n cannot be explained by differences in the kinetic constants for individual triplets. Hydroxylation of 14C-labeled preparations of (Pro-Pro-Gly)10 demonstrated that the ninth triplet was preferentially hydroxylated over any other triplet. The results were best explained by the hypothesis that prolyl hydroxylase has an asymmetric active site in which binding subsites are located adjacent to but not symmetrical with the catalytic subsite."}
{"id": "PMID:192270", "title": "A confirmation of the phase behavior of Escherichia coli cytoplasmic membrane lipids by X-ray diffraction.", "content": "The lipid fatty acid composition of the cytoplasmic membranes of Escherichia coli can be varied by growing an unsaturated fatty acid auxotroph in the presence of different fatty acid supplements. Electron spin resonance (ESR) studies of spin-label partitioning into the cytoplasmic membranes of different lipid fatty acid compositions as a function of temperature have been interpreted as indicating a broad order-to-disorder transition in the membrane lipids, the end points of the transition depending upon the fatty acid composition. We have utilized x-ray diffraction to confirm the ESR studies for three different fatty acid supplements (oleic, elaidic, and bromostearic). We found that the characteristic end-point temperatures detected by ESR were indeed the end-point temperatures of a broad order-to-disorder transition of the cytoplasmic membrane lipids. In addition, Patterson functions calculated from lamellar x-ray diffraction from partially oriented cytoplasmic membranes indicate a decrease in average membrane thickness upon fatty acid chain melting.", "contents": "A confirmation of the phase behavior of Escherichia coli cytoplasmic membrane lipids by X-ray diffraction. The lipid fatty acid composition of the cytoplasmic membranes of Escherichia coli can be varied by growing an unsaturated fatty acid auxotroph in the presence of different fatty acid supplements. Electron spin resonance (ESR) studies of spin-label partitioning into the cytoplasmic membranes of different lipid fatty acid compositions as a function of temperature have been interpreted as indicating a broad order-to-disorder transition in the membrane lipids, the end points of the transition depending upon the fatty acid composition. We have utilized x-ray diffraction to confirm the ESR studies for three different fatty acid supplements (oleic, elaidic, and bromostearic). We found that the characteristic end-point temperatures detected by ESR were indeed the end-point temperatures of a broad order-to-disorder transition of the cytoplasmic membrane lipids. In addition, Patterson functions calculated from lamellar x-ray diffraction from partially oriented cytoplasmic membranes indicate a decrease in average membrane thickness upon fatty acid chain melting."}
{"id": "PMID:192271", "title": "Inhibition of Escherichia coli growth and respiration by polymyxin B covalently attached to agarose beads.", "content": "Polymyxin B was attached to agarose beads by stable covalent bonds and the antimicrobial activity of the immobilized peptide was examined. Polymyxin-agarose inhibited the growth of Escherichia coli and Pseudomonas aeruginosa, but not Bacillus subtilis. In addition, the respiration of E. coli, E. coli spheroplasts, and B. subtilis protoplasts was inhibited by immobilized polymyxin, whereas the respiration of B. subtilis was unaffected by polymyxin-agarose. The activity of polymyxin-agarose was not due to the release of free peptide from the derivative. These data indicate that polymyxin can inhibit the growth and respiration of gram-negative bacteria by interacting with the outer surface of these cells. It is proposed that perturbation of outer membrane structure by polymyxin-agarose indirectly affected the selective permeability of the inner membrane and inhibited respiration. The results of this study emphasize the importance of outer membrane structural integrity for the normal functions of gram-negative bacteria.", "contents": "Inhibition of Escherichia coli growth and respiration by polymyxin B covalently attached to agarose beads. Polymyxin B was attached to agarose beads by stable covalent bonds and the antimicrobial activity of the immobilized peptide was examined. Polymyxin-agarose inhibited the growth of Escherichia coli and Pseudomonas aeruginosa, but not Bacillus subtilis. In addition, the respiration of E. coli, E. coli spheroplasts, and B. subtilis protoplasts was inhibited by immobilized polymyxin, whereas the respiration of B. subtilis was unaffected by polymyxin-agarose. The activity of polymyxin-agarose was not due to the release of free peptide from the derivative. These data indicate that polymyxin can inhibit the growth and respiration of gram-negative bacteria by interacting with the outer surface of these cells. It is proposed that perturbation of outer membrane structure by polymyxin-agarose indirectly affected the selective permeability of the inner membrane and inhibited respiration. The results of this study emphasize the importance of outer membrane structural integrity for the normal functions of gram-negative bacteria."}
{"id": "PMID:192272", "title": "Near-infrared magnetic circular dichroism of cytochrome c'.", "content": "The near-infrared magnetic circular dichroism (MCD) of Rhodospirillum rubrum, Chromatium vinosum, and Rhodopseudomonas palustris cytochromes c' are reported. The spectra of the reduced protein are very similar to those of deoxymyoglobin. The spectra of the oxidized proteins in the pD range 1-13 can be analyzed on the basis of four species A, B, C, and D. The existence of nine species, reported in a recent electron paramagnetic resonance study, is not substantiated. The MCD spectra support the assignment of B as high spin and C and D as low spin. The MCD of species A is close to that of high-spin proteins and does not support the recently proposed assignment of a mixed high- and intermediate-spin ground state for this species. The energies of the near-IR electronic transitions of all four oxidized species point to axial ligation via oxygen, assuming histidine to be the opposite axial ligand. Unfortunately, insufficient model compounds with ligation by carboxyl or hydroxyl moieties exist to enable more precise assignments.", "contents": "Near-infrared magnetic circular dichroism of cytochrome c'. The near-infrared magnetic circular dichroism (MCD) of Rhodospirillum rubrum, Chromatium vinosum, and Rhodopseudomonas palustris cytochromes c' are reported. The spectra of the reduced protein are very similar to those of deoxymyoglobin. The spectra of the oxidized proteins in the pD range 1-13 can be analyzed on the basis of four species A, B, C, and D. The existence of nine species, reported in a recent electron paramagnetic resonance study, is not substantiated. The MCD spectra support the assignment of B as high spin and C and D as low spin. The MCD of species A is close to that of high-spin proteins and does not support the recently proposed assignment of a mixed high- and intermediate-spin ground state for this species. The energies of the near-IR electronic transitions of all four oxidized species point to axial ligation via oxygen, assuming histidine to be the opposite axial ligand. Unfortunately, insufficient model compounds with ligation by carboxyl or hydroxyl moieties exist to enable more precise assignments."}
{"id": "PMID:192273", "title": "Stereochemistry of the porphyrin-protein bond of cytochrome c. Stereochemical comparison of Rhodospirillum rubrum, yeast, and horse heart porphyrins c.", "content": "Porphyrins c have been obtained from Rhodospirillum rubrum cytochrome c2, yeast cytochrome c, and horse heart cytochrome c and compared using proton magnetic resonance and circular dichroism. Identity of the spectra establishes that chemically and stereochemically the three porphyrins c are identical. Since the stereochemistry of the porphyrin alpha-thioether linkage is not affected in the conversion to porphyrin c, the stereochemistry at the porphyrin alpha-thioether bonds among the corresponding cytochromes c also must be the same. Differences between the proton magnetic resonance of R. rubrum cytochrome c2 and horse heart cytochrome c which were rationalized by invoking an opposite stereochemistry at these condensation sites (Smith, G. M., and Kamen, M. D. (1974), Proc. Natl. Acad. Sci. U.S.A. 71, 4303) must therefore be attributed to other factors.", "contents": "Stereochemistry of the porphyrin-protein bond of cytochrome c. Stereochemical comparison of Rhodospirillum rubrum, yeast, and horse heart porphyrins c. Porphyrins c have been obtained from Rhodospirillum rubrum cytochrome c2, yeast cytochrome c, and horse heart cytochrome c and compared using proton magnetic resonance and circular dichroism. Identity of the spectra establishes that chemically and stereochemically the three porphyrins c are identical. Since the stereochemistry of the porphyrin alpha-thioether linkage is not affected in the conversion to porphyrin c, the stereochemistry at the porphyrin alpha-thioether bonds among the corresponding cytochromes c also must be the same. Differences between the proton magnetic resonance of R. rubrum cytochrome c2 and horse heart cytochrome c which were rationalized by invoking an opposite stereochemistry at these condensation sites (Smith, G. M., and Kamen, M. D. (1974), Proc. Natl. Acad. Sci. U.S.A. 71, 4303) must therefore be attributed to other factors."}
{"id": "PMID:192274", "title": "Synthesis and uptake of gangliosides by choleragen-responsive human fibroblasts.", "content": "Human fibroblasts, cultured in medium containing 10% fetal calf serum, responded dramatically to choleragen with an increase in cyclic adenosine monophosphate content to greater than 48 times basal levels. Analysis of these cells for gangliosides indicated that the major ganglioside was N-acetylneuraminylgalactosylglucosylceramide (GM3) with trace amounts (less than or equal to 100 pmol/mg of protein) of other gangliosides including GM1, the putative choleragen receptor. Although the cells contained three glycosyltransferases required for ganglioside synthesis, the N-acetylgalactosaminyltransferase activity necessary for the conversion of GM3 to more complex gangliosides was not detected. When the cells were grown in medium containing [14C]galactose or N-acety[3H]mannosamine, however, all of the gangliosides became labeled, indicating that the cells can synthesize complex gangliosides. Although fetal calf serum contains gangliosides including GM1, [3H]GM1 was taken up poorly from the growth medium and uptake at the rate observed could have accounted for less than 2% of the GM1 content of the cells. When the cells were incubated in chemically defined medium containing [3H]GM1 at the concentrations present in fetal calf serum, rapid uptake of the ganglioside occurred and the total GM1 content of the cells increased threefold in less than 3  h. Thus, although the cells are capable of binding exogenous gangliosides, the gangliosides in fetal calf serum are in a form not readily available to the cells.", "contents": "Synthesis and uptake of gangliosides by choleragen-responsive human fibroblasts. Human fibroblasts, cultured in medium containing 10% fetal calf serum, responded dramatically to choleragen with an increase in cyclic adenosine monophosphate content to greater than 48 times basal levels. Analysis of these cells for gangliosides indicated that the major ganglioside was N-acetylneuraminylgalactosylglucosylceramide (GM3) with trace amounts (less than or equal to 100 pmol/mg of protein) of other gangliosides including GM1, the putative choleragen receptor. Although the cells contained three glycosyltransferases required for ganglioside synthesis, the N-acetylgalactosaminyltransferase activity necessary for the conversion of GM3 to more complex gangliosides was not detected. When the cells were grown in medium containing [14C]galactose or N-acety[3H]mannosamine, however, all of the gangliosides became labeled, indicating that the cells can synthesize complex gangliosides. Although fetal calf serum contains gangliosides including GM1, [3H]GM1 was taken up poorly from the growth medium and uptake at the rate observed could have accounted for less than 2% of the GM1 content of the cells. When the cells were incubated in chemically defined medium containing [3H]GM1 at the concentrations present in fetal calf serum, rapid uptake of the ganglioside occurred and the total GM1 content of the cells increased threefold in less than 3  h. Thus, although the cells are capable of binding exogenous gangliosides, the gangliosides in fetal calf serum are in a form not readily available to the cells."}
{"id": "PMID:192275", "title": "Enzymatic and chemical oxidation of gangliosides in cultured cells: effects of choleragen.", "content": "Cell surface glycolipids of normal human fibroblasts and NCTC2071 cells (transformed mouse fibroblasts) were labeled by incubating the intact cells with either galactose oxidase or sodium periodate, followed by reduction of the oxidized sugar residues with NaB3H4. In intact human fibroblasts, incorporation of 3H was increased with increasing time of exposure to galactose oxidase prior to treatment with NaB3H4. Following limited exposure to galactose oxidase, more label was incorporated into the larger glycolipids. Although labeling of the monosialoganglioside GM1 was maximal by 16 h, not all of the GM1 in the intact cells appeared to be accessible to galactose oxidase, since 10 to 12 times more GM1 was labeled when cells were disrupted before incubation with the enzyme. The human fibroblasts contained approximately 8 X 10(6) molecules of GM1 per cell. Maximal binding of choleragen (5 X 10(5) molecules of [125I]choleragen per cell) completely prevented cholevented oxidation of GM1 in intact fibroblasts by galactose oxidase but only partially protected the sialic acid moiety of GM1 from oxidation by periodate. Choleragen had little effect on the enzymatic or chemical oxidation of other glycolipids. NCTC 2071 cells do not contain endogenous GM1 but incorporate exogenous GM1 from the culture medium. When bound to NCTC 2071 cells, exogenous GM1 was protected by choleragen from oxidation by galactose oxidase or whether endogenous or taken up from the incubation medium, are, after interaction with choleragen, less accessible to oxidation by periodate or galactose oxidase.", "contents": "Enzymatic and chemical oxidation of gangliosides in cultured cells: effects of choleragen. Cell surface glycolipids of normal human fibroblasts and NCTC2071 cells (transformed mouse fibroblasts) were labeled by incubating the intact cells with either galactose oxidase or sodium periodate, followed by reduction of the oxidized sugar residues with NaB3H4. In intact human fibroblasts, incorporation of 3H was increased with increasing time of exposure to galactose oxidase prior to treatment with NaB3H4. Following limited exposure to galactose oxidase, more label was incorporated into the larger glycolipids. Although labeling of the monosialoganglioside GM1 was maximal by 16 h, not all of the GM1 in the intact cells appeared to be accessible to galactose oxidase, since 10 to 12 times more GM1 was labeled when cells were disrupted before incubation with the enzyme. The human fibroblasts contained approximately 8 X 10(6) molecules of GM1 per cell. Maximal binding of choleragen (5 X 10(5) molecules of [125I]choleragen per cell) completely prevented cholevented oxidation of GM1 in intact fibroblasts by galactose oxidase but only partially protected the sialic acid moiety of GM1 from oxidation by periodate. Choleragen had little effect on the enzymatic or chemical oxidation of other glycolipids. NCTC 2071 cells do not contain endogenous GM1 but incorporate exogenous GM1 from the culture medium. When bound to NCTC 2071 cells, exogenous GM1 was protected by choleragen from oxidation by galactose oxidase or whether endogenous or taken up from the incubation medium, are, after interaction with choleragen, less accessible to oxidation by periodate or galactose oxidase."}
{"id": "PMID:192276", "title": "Use of a fluorescent probe to determine the viscosity of LM cell membranes with altered phospholipid compositions.", "content": "The phospholipid compostition of LM cells grown in tissue culture was altered by substituting ethanolamine for choline in the growth medium. The plasma membrane isolated from cells grown in medium conatining ethanolamine for 83 h had a sixfold increase in the ratio of phosphatidylethanolamine to phosphatidylcholine, the two major phospholipid classes. This was accompanied by small changes in other lipid components of the membrane. There was also a sixfold increase in the amount of triacylglycerols and alkyldiacylglycerols which were not associated with the membrane fraction of the cell. No significant changes occurred in the lipid composition of cells during growth in choline containing medium. The viscosity of plasma membranes was studied in whole cells and isolated membranes using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene. Plasma membranes isolated from ethanolamine-supplemented cells had greater viscosities than membranes isolated from choline-supplemented cells. When whole cells were labeled with the fluorescent probe, the opposite trend in the apparent membrane viscosity was observed. This was due primarily to the probe penetrating into nonmembranous neutral lipids rather than remaining localized in the surface membrane of the cells. Since the enthanolamine-supplemented cells contained more low viscosity neutral lipids, the whole cells gave an apparently lower viscosity as compared with choline-supplemented cells, thus, measurements carried out on whole cells gave an inaccurate determination of the viscosity of the surface membrane.", "contents": "Use of a fluorescent probe to determine the viscosity of LM cell membranes with altered phospholipid compositions. The phospholipid compostition of LM cells grown in tissue culture was altered by substituting ethanolamine for choline in the growth medium. The plasma membrane isolated from cells grown in medium conatining ethanolamine for 83 h had a sixfold increase in the ratio of phosphatidylethanolamine to phosphatidylcholine, the two major phospholipid classes. This was accompanied by small changes in other lipid components of the membrane. There was also a sixfold increase in the amount of triacylglycerols and alkyldiacylglycerols which were not associated with the membrane fraction of the cell. No significant changes occurred in the lipid composition of cells during growth in choline containing medium. The viscosity of plasma membranes was studied in whole cells and isolated membranes using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene. Plasma membranes isolated from ethanolamine-supplemented cells had greater viscosities than membranes isolated from choline-supplemented cells. When whole cells were labeled with the fluorescent probe, the opposite trend in the apparent membrane viscosity was observed. This was due primarily to the probe penetrating into nonmembranous neutral lipids rather than remaining localized in the surface membrane of the cells. Since the enthanolamine-supplemented cells contained more low viscosity neutral lipids, the whole cells gave an apparently lower viscosity as compared with choline-supplemented cells, thus, measurements carried out on whole cells gave an inaccurate determination of the viscosity of the surface membrane."}
{"id": "PMID:192277", "title": "Fluorescent derivatives of the pyruvate dehydrogenase component of the Escherichia coli pyruvate dehydrogenase complex.", "content": "One sulfhydryl group per polypeptide chain of the pyruvate dehydrogenase component of the pyruvate dehydrogenase multienzyme complex from Escherichia coli was selectively labeled with N-[P-(2-benzoxazoyl)phenyl]-maleimide (NBM), 4-dimethylamino-4-magnitude of-maleimidostilbene (NSM), and N-(4-dimethylamino-3,5-dinitrophenyl)maleimide (DDPM) in 0.05 M potassium phosphate (pH 7). Modification of the sulfhydryl group did not alter the enzymatic activity or the binding of 8-anilino-1-naphthalenesulfonate (ANS) or thiochrome diphosphate to the enzyme. The fluorescence of the NBM or NSM coupled to the sulfhydryl group on the enzyme was quenched by binding to the enzyme of the substrate pyruvate the coenzyme thiamine diphosphate, the coenzyme analogue thiochrome diphosphate, the regulatory ligands acetyl-CoA, GTP, and phosphoenolpyruvate, and the acetyl-CoA analogue, ANS. Fluorescence energy transfer measurements were carried out for the enzyme-bound donor-acceptor pairs NBM-ANS, NBM-thiochrome diphosphate ANS-DDPM, and thiochrome diphosphate-DDM. The results indicate that the modified sulfhydryl group is more than 40 A from the active site and approximately 49 A from the acetyl-CoA regulatory site. Thus, a conformational change must accompany the binding of ligands to the regulatory and catalytic sites. Anisotropy depolarization measurements with ANS bound on the isolated pyruvate dehydrogenase in 0.05 M potassium phosphate (pH 7.0) suggest that under these conditions the enzyme is dimeric.", "contents": "Fluorescent derivatives of the pyruvate dehydrogenase component of the Escherichia coli pyruvate dehydrogenase complex. One sulfhydryl group per polypeptide chain of the pyruvate dehydrogenase component of the pyruvate dehydrogenase multienzyme complex from Escherichia coli was selectively labeled with N-[P-(2-benzoxazoyl)phenyl]-maleimide (NBM), 4-dimethylamino-4-magnitude of-maleimidostilbene (NSM), and N-(4-dimethylamino-3,5-dinitrophenyl)maleimide (DDPM) in 0.05 M potassium phosphate (pH 7). Modification of the sulfhydryl group did not alter the enzymatic activity or the binding of 8-anilino-1-naphthalenesulfonate (ANS) or thiochrome diphosphate to the enzyme. The fluorescence of the NBM or NSM coupled to the sulfhydryl group on the enzyme was quenched by binding to the enzyme of the substrate pyruvate the coenzyme thiamine diphosphate, the coenzyme analogue thiochrome diphosphate, the regulatory ligands acetyl-CoA, GTP, and phosphoenolpyruvate, and the acetyl-CoA analogue, ANS. Fluorescence energy transfer measurements were carried out for the enzyme-bound donor-acceptor pairs NBM-ANS, NBM-thiochrome diphosphate ANS-DDPM, and thiochrome diphosphate-DDM. The results indicate that the modified sulfhydryl group is more than 40 A from the active site and approximately 49 A from the acetyl-CoA regulatory site. Thus, a conformational change must accompany the binding of ligands to the regulatory and catalytic sites. Anisotropy depolarization measurements with ANS bound on the isolated pyruvate dehydrogenase in 0.05 M potassium phosphate (pH 7.0) suggest that under these conditions the enzyme is dimeric."}
{"id": "PMID:192278", "title": "Lipoprotein lipase. Isolation and characterization of a second enzyme species from postheparin plasma.", "content": "A lipoprotein lipase species (mol wt 69 250) has been isolated from rat postheparin plasma, which differs from the low-molecular-weight species previously characterized in its amino acid composition and hexosamine content, and in its lower affinity for triglyceride-rich lipoprotein substrates. However, both enzymes are activated by the same coprotein (C-terminal glutamic acid, apo-C-2) from human very low density lipoprotein and have a similar specificity for lipid esters. Neither purified enzyme is activated by heparin. Both are inhibited by molar sodium chloride. Both enzyme species can be recovered from the same plasma samples. The possible relationship of these proteins to the different functional lipoprotein lipase activities of muscle and adipose tissues is discussed.", "contents": "Lipoprotein lipase. Isolation and characterization of a second enzyme species from postheparin plasma. A lipoprotein lipase species (mol wt 69 250) has been isolated from rat postheparin plasma, which differs from the low-molecular-weight species previously characterized in its amino acid composition and hexosamine content, and in its lower affinity for triglyceride-rich lipoprotein substrates. However, both enzymes are activated by the same coprotein (C-terminal glutamic acid, apo-C-2) from human very low density lipoprotein and have a similar specificity for lipid esters. Neither purified enzyme is activated by heparin. Both are inhibited by molar sodium chloride. Both enzyme species can be recovered from the same plasma samples. The possible relationship of these proteins to the different functional lipoprotein lipase activities of muscle and adipose tissues is discussed."}
{"id": "PMID:192279", "title": "Purification and characterization of Novikoff ascites tumor protein kinase.", "content": "A protein kinase, designed KII, has been purified 5000-fold from Novikoff ascites tumor cells. The purification procedure also allows for the purification of a second major protein kinase, designated KI, as well as RNA polymerase I and II. Purified KII has a sedimentation constant of 7.6 S and a Stokes radius of 39 A, suggesting a molecular weight of about 122000. Polyacrylamide gel electrophoresis of the enzyme in the presence of sodium dodecyl sulfate suggests the enzyme is composed of subunits of molecular weights 44 000, 40 000, and 26 000 present in a molar ratio of 1:1:2. Incubation of the enzyme alone in the presence of [gamma-32P]ATP results in the phosphorylation of the 26 000-dalton subunit. Protein kinase II actively phosphorylates phosvitin, casein, and nonhistone chromosomal proteins but does not phosphorylate basic proteins such as histones or protamine to an appreciable extent. Km values of 3.6 micron for ATP and 6.5 micronM for GTP were determined in the presence of 4mM Mg2+. The enzyme is neither stimulated by cyclic adenosine 3',5'-monophosphate or cyclic guanosine 3', 5'-monophosphate nor inhibited by the regulatory subunit of rabbit muscle protein kinase. Its activity is stimulated by KCl at concentrations below 0.2 M and inhibited by higher concentrations.", "contents": "Purification and characterization of Novikoff ascites tumor protein kinase. A protein kinase, designed KII, has been purified 5000-fold from Novikoff ascites tumor cells. The purification procedure also allows for the purification of a second major protein kinase, designated KI, as well as RNA polymerase I and II. Purified KII has a sedimentation constant of 7.6 S and a Stokes radius of 39 A, suggesting a molecular weight of about 122000. Polyacrylamide gel electrophoresis of the enzyme in the presence of sodium dodecyl sulfate suggests the enzyme is composed of subunits of molecular weights 44 000, 40 000, and 26 000 present in a molar ratio of 1:1:2. Incubation of the enzyme alone in the presence of [gamma-32P]ATP results in the phosphorylation of the 26 000-dalton subunit. Protein kinase II actively phosphorylates phosvitin, casein, and nonhistone chromosomal proteins but does not phosphorylate basic proteins such as histones or protamine to an appreciable extent. Km values of 3.6 micron for ATP and 6.5 micronM for GTP were determined in the presence of 4mM Mg2+. The enzyme is neither stimulated by cyclic adenosine 3',5'-monophosphate or cyclic guanosine 3', 5'-monophosphate nor inhibited by the regulatory subunit of rabbit muscle protein kinase. Its activity is stimulated by KCl at concentrations below 0.2 M and inhibited by higher concentrations."}
{"id": "PMID:192280", "title": "Analysis and computer simulation of aerobic oxidation of reduced nicotinamide adenine dinucleotide catalyzed by horseradish peroxidase.", "content": "Under suitable experimental conditions the aerobic oxidation of NADH catalyzed by horseradish peroxidase occurred in four characteristic phases: initial burst, induction phase, steady state, and termination. A trace amount of H2O2 present in the NADH solution brought about initial burst in the formation of oxyperoxidase. About 2 mol of oxyperoxidase was formed per mol of H2O2. When a considerable amount of the ferric enzyme still remained, the initial burst was followed by an induction phase. In this phase the rate of oxyperoxidase formation from the ferric enzyme increased with the decrease of the ferric enzyme and an approximately exponential increase of oxyperoxidase was observed. A rapid oxidation of NADH suddenly began at the end of the induction phase and the oxidation continued at a relatively constant rate. In the steady state, oxygen was consumed and H2O2 accumulated. A drastic terminating reaction suddenly set in when the oxygen concentration decreased under a certain level. During the reaction, H2O2 disappeared accompanying an accelerated oxidation of NADH and the enzyme returned to the ferric form after a transient increase of peroxidase compound II. Time courses of NADH oxidation, O2 consumption, H2O2 accumulation, and formation of enzyme intermediates could be simulated with an electronic computer using 11 elementary reactions and 9 rate equations. The results were also discussed in relation to the mechanism for oscillatory responses of the reaction that appeared in an open system with a continuous supply of oxygen.", "contents": "Analysis and computer simulation of aerobic oxidation of reduced nicotinamide adenine dinucleotide catalyzed by horseradish peroxidase. Under suitable experimental conditions the aerobic oxidation of NADH catalyzed by horseradish peroxidase occurred in four characteristic phases: initial burst, induction phase, steady state, and termination. A trace amount of H2O2 present in the NADH solution brought about initial burst in the formation of oxyperoxidase. About 2 mol of oxyperoxidase was formed per mol of H2O2. When a considerable amount of the ferric enzyme still remained, the initial burst was followed by an induction phase. In this phase the rate of oxyperoxidase formation from the ferric enzyme increased with the decrease of the ferric enzyme and an approximately exponential increase of oxyperoxidase was observed. A rapid oxidation of NADH suddenly began at the end of the induction phase and the oxidation continued at a relatively constant rate. In the steady state, oxygen was consumed and H2O2 accumulated. A drastic terminating reaction suddenly set in when the oxygen concentration decreased under a certain level. During the reaction, H2O2 disappeared accompanying an accelerated oxidation of NADH and the enzyme returned to the ferric form after a transient increase of peroxidase compound II. Time courses of NADH oxidation, O2 consumption, H2O2 accumulation, and formation of enzyme intermediates could be simulated with an electronic computer using 11 elementary reactions and 9 rate equations. The results were also discussed in relation to the mechanism for oscillatory responses of the reaction that appeared in an open system with a continuous supply of oxygen."}
{"id": "PMID:192281", "title": "Mechanism of thyroxine-mediated oxidation of reduced nicotinamide adenine dinucleotide in peroxidase-H2O2 system.", "content": "The oxidation of reduced nicotinamide adenine dinucleotide (NADH) by the horseradish peroxidase (HRP)-H2O2 system is greatly increased by the addition of thyroxine or related compounds. On the basis of a study of the rate of NADH oxidation in the presence of various concentrations of thyroxine, it is clear that thyroxine acts as a catalyst for NADH oxidation. Spectral changes of a HRP-H2O2 complex (compound I) indicate that thyroxine acts as an electron donor to both compounds I and II. The rate of electron donation from thyroxine is much faster than that from NADH. The HRP-H2O2 system requires 0.83 mol of O2 for the oxidation of 1 mol of NADH. Ferricytochrome c is reduced to ferrocytochrome c by the system, and causes an inhibition of O2 consumption which can be abolished by superoxide dismutase. JUDGING FROM THE INHIBITION OF O2 uptake by ferricytochrome c, about 54% of the total flux of electrons from NADH to oxygen appears to proceed by way of O2-. These results suggest that the initial step of thyroxine-mediated NADH oxidation by HRP and H2O2 is the formation of oxidized thyroxine, a phenoxy radical, which attacks NADH to produce NAD.", "contents": "Mechanism of thyroxine-mediated oxidation of reduced nicotinamide adenine dinucleotide in peroxidase-H2O2 system. The oxidation of reduced nicotinamide adenine dinucleotide (NADH) by the horseradish peroxidase (HRP)-H2O2 system is greatly increased by the addition of thyroxine or related compounds. On the basis of a study of the rate of NADH oxidation in the presence of various concentrations of thyroxine, it is clear that thyroxine acts as a catalyst for NADH oxidation. Spectral changes of a HRP-H2O2 complex (compound I) indicate that thyroxine acts as an electron donor to both compounds I and II. The rate of electron donation from thyroxine is much faster than that from NADH. The HRP-H2O2 system requires 0.83 mol of O2 for the oxidation of 1 mol of NADH. Ferricytochrome c is reduced to ferrocytochrome c by the system, and causes an inhibition of O2 consumption which can be abolished by superoxide dismutase. JUDGING FROM THE INHIBITION OF O2 uptake by ferricytochrome c, about 54% of the total flux of electrons from NADH to oxygen appears to proceed by way of O2-. These results suggest that the initial step of thyroxine-mediated NADH oxidation by HRP and H2O2 is the formation of oxidized thyroxine, a phenoxy radical, which attacks NADH to produce NAD."}
{"id": "PMID:192282", "title": "Metal sites of copper-zinc superoxide dismutase.", "content": "Silver-copper and silver-cobalt proteins have been prepared in which Ag+ resides in the native copper site of superoxide dismutase and either Cu2+ of Co2+ reside in the zinc site. The electron paramagnetic resonance (EPR) spectrum of the copper and the visible absorption spectrum of the cobalt greatly resemble those of either Cu4 of Cu2,Cu2,Co2 proteins, respectively, in which the copper of the native copper sites has been reduced. It was found that, unlike cyanide, azide anion would not perturb the EPR spectrum of Ag2,Cu2 protein. Since azide produces the same perturbation upon the EPR spectrum of native and Cu2 proteins, it must bind to the copper and not the zinc of superoxide dismutase. A model of the metal sites of the enzyme has been fitted to a 3-A electron-density map using an interactive molecular graphics display. The model shows that histidine-61, which appears to bind both copper and zinc, does not lie in the plane of the copper and its three other histidine ligands, but occupies a position intermediate between planar and axial. This feature probably accounts for the rhombicity of the EPR spectrum and the activity of the enzyme.", "contents": "Metal sites of copper-zinc superoxide dismutase. Silver-copper and silver-cobalt proteins have been prepared in which Ag+ resides in the native copper site of superoxide dismutase and either Cu2+ of Co2+ reside in the zinc site. The electron paramagnetic resonance (EPR) spectrum of the copper and the visible absorption spectrum of the cobalt greatly resemble those of either Cu4 of Cu2,Cu2,Co2 proteins, respectively, in which the copper of the native copper sites has been reduced. It was found that, unlike cyanide, azide anion would not perturb the EPR spectrum of Ag2,Cu2 protein. Since azide produces the same perturbation upon the EPR spectrum of native and Cu2 proteins, it must bind to the copper and not the zinc of superoxide dismutase. A model of the metal sites of the enzyme has been fitted to a 3-A electron-density map using an interactive molecular graphics display. The model shows that histidine-61, which appears to bind both copper and zinc, does not lie in the plane of the copper and its three other histidine ligands, but occupies a position intermediate between planar and axial. This feature probably accounts for the rhombicity of the EPR spectrum and the activity of the enzyme."}
{"id": "PMID:192283", "title": "Effect of spin-labeled maleimide on 14S and 30S dyneins in solution and on demembranated ciliary axonemes.", "content": "The effects of N-1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)maleimide(SLM) on the pellet height response and ATPase activity of glycerinated Triton X-100 extracted cilia of Tetrahymena pyriformis have been studied. Preincubation of cilia with SLM caused complete inhibition of the pellet height response and an initial increase in ATPase activity followed upon longer exposure to SLM by inhibition of ATPase. The effect of SLM on extracted 30S dynein was the reverse of that for whole cilia: ATPase activity was increased when 30S dynein was added to a mixture of ATP and SLM and inhibited when the 30S dynein was preincubated with SLM. The activity of 14S dynein was only inhibited by SLM. Electron spin resonance spectra of ciliary axonemes that had reacted with SLM for various times showed that much of the covalently bound SLM was strongly immobilized even after 1 min of reaction, when ATPase activity increased twofold. The proportion of strongly immobilized label increased with longer times of reaction. Addition of ATP to SLM-labeled axonemes caused a small decrease in the height of the spectral peak corresponding to strongly immobilized label as compared with that of weakly immobilized label, indicating an increase in rotational freedom of some covalently bound label. The results suggest that ATP causes a conformation change affecting a sulfhydryl group(s) involved in the mechanochemical system. It was also shown that beta,gamma-methylene ATP(AMP-PCP) is an inhibitor of dynein ATPase. This analogue of ATP is not hydrolyzed by whole cilia or by the extracted dyneins and does not cause a pellet height response. With Mg2+ as divalent cation, AMP-PCP inhibits 30S dynein more than it inhibits 14S dynein; with Ca2+, the inhibition of 30S dynein is reduced, and there is no inhibition of 14S dynein. Under conditions where AMP-PCP inhibited 30S dynein ATPase it was much less effective than ATP in protecting against the loss of ATPase activity by SLM. Although SLM inhibited Mg2+-activated 14S and 30S dyneins in solution, it did not inhibit ciliary ATPase activity. These results support the view that at least 2 SH groups are involved in ciliary motility and that their reactivity to SH reagents depends on whether the dyneins are in situ or have been extracted.", "contents": "Effect of spin-labeled maleimide on 14S and 30S dyneins in solution and on demembranated ciliary axonemes. The effects of N-1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)maleimide(SLM) on the pellet height response and ATPase activity of glycerinated Triton X-100 extracted cilia of Tetrahymena pyriformis have been studied. Preincubation of cilia with SLM caused complete inhibition of the pellet height response and an initial increase in ATPase activity followed upon longer exposure to SLM by inhibition of ATPase. The effect of SLM on extracted 30S dynein was the reverse of that for whole cilia: ATPase activity was increased when 30S dynein was added to a mixture of ATP and SLM and inhibited when the 30S dynein was preincubated with SLM. The activity of 14S dynein was only inhibited by SLM. Electron spin resonance spectra of ciliary axonemes that had reacted with SLM for various times showed that much of the covalently bound SLM was strongly immobilized even after 1 min of reaction, when ATPase activity increased twofold. The proportion of strongly immobilized label increased with longer times of reaction. Addition of ATP to SLM-labeled axonemes caused a small decrease in the height of the spectral peak corresponding to strongly immobilized label as compared with that of weakly immobilized label, indicating an increase in rotational freedom of some covalently bound label. The results suggest that ATP causes a conformation change affecting a sulfhydryl group(s) involved in the mechanochemical system. It was also shown that beta,gamma-methylene ATP(AMP-PCP) is an inhibitor of dynein ATPase. This analogue of ATP is not hydrolyzed by whole cilia or by the extracted dyneins and does not cause a pellet height response. With Mg2+ as divalent cation, AMP-PCP inhibits 30S dynein more than it inhibits 14S dynein; with Ca2+, the inhibition of 30S dynein is reduced, and there is no inhibition of 14S dynein. Under conditions where AMP-PCP inhibited 30S dynein ATPase it was much less effective than ATP in protecting against the loss of ATPase activity by SLM. Although SLM inhibited Mg2+-activated 14S and 30S dyneins in solution, it did not inhibit ciliary ATPase activity. These results support the view that at least 2 SH groups are involved in ciliary motility and that their reactivity to SH reagents depends on whether the dyneins are in situ or have been extracted."}
{"id": "PMID:192284", "title": "Detection of the kinetics of biochemical reactions with oxygen using exchange broadening in the ESR spectra of nitroxide radicals.", "content": "To detect changes in the oxygen concentration during biochemical reactions, the exchange broadening in the ESR spectra of nitroxide radicals caused by the dissolved oxygen, has been used. The measurements have been carried out using changes in the width either of the proton hyperfine structure components or of the nitrogen hyperfine structure line with an unresolved proton structure. Detection of mitochondrial respiration in a volume of about 10(-3) cm 3 and respiration for 100 +/- 5 liver cells in a volume of about 10(-4) cm3 has been carried out.", "contents": "Detection of the kinetics of biochemical reactions with oxygen using exchange broadening in the ESR spectra of nitroxide radicals. To detect changes in the oxygen concentration during biochemical reactions, the exchange broadening in the ESR spectra of nitroxide radicals caused by the dissolved oxygen, has been used. The measurements have been carried out using changes in the width either of the proton hyperfine structure components or of the nitrogen hyperfine structure line with an unresolved proton structure. Detection of mitochondrial respiration in a volume of about 10(-3) cm 3 and respiration for 100 +/- 5 liver cells in a volume of about 10(-4) cm3 has been carried out."}
{"id": "PMID:192285", "title": "Funiculosin: an antibiotic with antimycin-like inhibitory properties.", "content": "The antibiotic funiculosin mimics the action of antimycin in several ways. It inhibits the oxidation of NADH and succinate, but not TMPD+ascorbate. The titer for maximal inhibition in Mg2+-ATP particles (0.4-0.6 nmol/mg protein) is close to the concentrations of cytochromes b and cc1. Funiculosin also induces the oxidation of cytochromes cc1 and an extra reduction of cytochrome b in the aerobic steady state, and it inhibits duroquinol-cytochrome c reductase activity in isolated Complex III. The location of the funiculosin binding site is clearly similar to that of antimycin. In addition, funiculosin, like antimycin, prevents electron transport from duroquinol to cytochrome b in isolated Complex III if the complex is pre-reduced with ascorbate. Funiculosin and antimycin differ, however, in the manner in which they modulate the reduction of cytochrome b by ascorbate+TMPD.", "contents": "Funiculosin: an antibiotic with antimycin-like inhibitory properties. The antibiotic funiculosin mimics the action of antimycin in several ways. It inhibits the oxidation of NADH and succinate, but not TMPD+ascorbate. The titer for maximal inhibition in Mg2+-ATP particles (0.4-0.6 nmol/mg protein) is close to the concentrations of cytochromes b and cc1. Funiculosin also induces the oxidation of cytochromes cc1 and an extra reduction of cytochrome b in the aerobic steady state, and it inhibits duroquinol-cytochrome c reductase activity in isolated Complex III. The location of the funiculosin binding site is clearly similar to that of antimycin. In addition, funiculosin, like antimycin, prevents electron transport from duroquinol to cytochrome b in isolated Complex III if the complex is pre-reduced with ascorbate. Funiculosin and antimycin differ, however, in the manner in which they modulate the reduction of cytochrome b by ascorbate+TMPD."}
{"id": "PMID:192286", "title": "A study of calcium pump activity of lysosomes from rat renal cortex.", "content": "Fractions rich in either primary or secondary lysosomes were prepared from rat renal cortex by differential centrifugation and evaluated for their capacity for net calcium uptake. No uptake was observed in the absence of ATP. A vigorous uptake did take place in the presence of ATP but it was largely prevented by azide and other inhibitors of mitochondrial calcium uptake, suggesting that it was attributable to contamination by mitochondria. Evidence was obtained for an inhibitory influence of the secondary lysosomal fraction on mitochondrial calcium uptake.", "contents": "A study of calcium pump activity of lysosomes from rat renal cortex. Fractions rich in either primary or secondary lysosomes were prepared from rat renal cortex by differential centrifugation and evaluated for their capacity for net calcium uptake. No uptake was observed in the absence of ATP. A vigorous uptake did take place in the presence of ATP but it was largely prevented by azide and other inhibitors of mitochondrial calcium uptake, suggesting that it was attributable to contamination by mitochondria. Evidence was obtained for an inhibitory influence of the secondary lysosomal fraction on mitochondrial calcium uptake."}
{"id": "PMID:192287", "title": "Photooxidation of chlorophyll in spinach chloroplasts between 10 and 180 K.", "content": "Electron paramagnetic resonance (EPR) and optical absorbance difference spectra and kinetics upon illumination by saturating flashes and continuous light of spinach chloroplasts frozen under various conditions were measured between 10 and 180 K. 1. At 100 K illumination with continuous light caused an EPR signal which decayed during the light in about 30 ms. This change is probably due to the reduction of P+-680, the oxidized primary electron donor of Photosystem II, by a secondary electron donor, cytochrome b-559. Flash illumination yielded the previously observed rapid (2 ms) transient. This transient has been ascribed to a back-reaction of the two primary reagents of Photosystem II (Malkin, R. and Bearden, A.J. (1975) Biochim. Biophys. Acta 396, 250-259; Visser, J.W.M. (1975) Thesis, Leiden). 2. Between 10 and 40 K, illumination with continuous light showed a transient which decayed in about 500 ms. The extent decreased with increasing temperature. However, the half time appeared to be temperature independent. This signal was also attributed to P+-680. 3. At 180 K it appeared to be impossible to observe the 2 and 30 ms components in dark frozen chloroplasts. However, they could be observed again if two short saturating flashes were given shortly before freezing. These changes seem to be dependent on the S-state of the reaction center. 4. After oxidizing the sample with ferricyanide (Eh = 540 mV), the light induced absorbance difference spectrum showed a bleaching near 676 nm. This change is ascribed to the irreversible oxidation of a dimeric chlorophyll molecule which acts as electron donor to P+-680 under these conditions. 5. Titration curves of the irreversible light-induced absorbance change at 676 nm and the irreversible light-induced EPR change near g = 2.00 provide strong evidence that these two changes reflect the same compound. Finally, a model is given to explain the observed reactions of Photosystem II at 10-180 K. The model involves three different ultimate and one intermediate electron donor to P+-680 at these temperatures.", "contents": "Photooxidation of chlorophyll in spinach chloroplasts between 10 and 180 K. Electron paramagnetic resonance (EPR) and optical absorbance difference spectra and kinetics upon illumination by saturating flashes and continuous light of spinach chloroplasts frozen under various conditions were measured between 10 and 180 K. 1. At 100 K illumination with continuous light caused an EPR signal which decayed during the light in about 30 ms. This change is probably due to the reduction of P+-680, the oxidized primary electron donor of Photosystem II, by a secondary electron donor, cytochrome b-559. Flash illumination yielded the previously observed rapid (2 ms) transient. This transient has been ascribed to a back-reaction of the two primary reagents of Photosystem II (Malkin, R. and Bearden, A.J. (1975) Biochim. Biophys. Acta 396, 250-259; Visser, J.W.M. (1975) Thesis, Leiden). 2. Between 10 and 40 K, illumination with continuous light showed a transient which decayed in about 500 ms. The extent decreased with increasing temperature. However, the half time appeared to be temperature independent. This signal was also attributed to P+-680. 3. At 180 K it appeared to be impossible to observe the 2 and 30 ms components in dark frozen chloroplasts. However, they could be observed again if two short saturating flashes were given shortly before freezing. These changes seem to be dependent on the S-state of the reaction center. 4. After oxidizing the sample with ferricyanide (Eh = 540 mV), the light induced absorbance difference spectrum showed a bleaching near 676 nm. This change is ascribed to the irreversible oxidation of a dimeric chlorophyll molecule which acts as electron donor to P+-680 under these conditions. 5. Titration curves of the irreversible light-induced absorbance change at 676 nm and the irreversible light-induced EPR change near g = 2.00 provide strong evidence that these two changes reflect the same compound. Finally, a model is given to explain the observed reactions of Photosystem II at 10-180 K. The model involves three different ultimate and one intermediate electron donor to P+-680 at these temperatures."}
{"id": "PMID:192288", "title": "Cytochrome c-551.5 (c7) from Desulfuromonas acetoxidans.", "content": "Cytochrome c-551.5 of the anaerobic sulfur-reducing bacterium Desulfuromonas acetoxidans has been purified to homogeneity and characterized. It elicits absorption bands at 551.5, 522.5 and 418 nm in the reduced form; the absorptivity ratio Aalpha(red)/A280nm(ox) equals 3.8 for the pure preparation. The molecular weight was estimated to be 9800 by gel filtration. Determination of the amion acid composition and analysis of the N-terminal amino acid sequence showed the cytochrome to be identical with the threehaem cytochrome c-551.5 (c7) isolated from the syntrophic mixed culture Chloropseudomonas ethylica strain 2K. The occurrence of multihaem cytochromes c in bacteria is discussed.", "contents": "Cytochrome c-551.5 (c7) from Desulfuromonas acetoxidans. Cytochrome c-551.5 of the anaerobic sulfur-reducing bacterium Desulfuromonas acetoxidans has been purified to homogeneity and characterized. It elicits absorption bands at 551.5, 522.5 and 418 nm in the reduced form; the absorptivity ratio Aalpha(red)/A280nm(ox) equals 3.8 for the pure preparation. The molecular weight was estimated to be 9800 by gel filtration. Determination of the amion acid composition and analysis of the N-terminal amino acid sequence showed the cytochrome to be identical with the threehaem cytochrome c-551.5 (c7) isolated from the syntrophic mixed culture Chloropseudomonas ethylica strain 2K. The occurrence of multihaem cytochromes c in bacteria is discussed."}
{"id": "PMID:192289", "title": "The reduction of porphyrin cytochrome c by hydrated electrons and the subsequent electron transfer reaction from reduced porphyrin cytochrome c to ferricytochrome c.", "content": "1. Hydrated electrons, produced by pulse radiolysis react with porphyrin cytochrome c with a bimolecular rate constant of 3-10(10) M-1 S-1 at 21 degrees C and pH 7.4. 2. After the reduction step an absorbance change with a half-life of 5 microns is observed with the spectral range of 430-470 nm. A relatively stable intermediate then decays with a half-life of 15 s. 3. The spectrum of the intermediate observed 50 microns after the generation of hydrated electrons shows a broad absorption band between 600 and 700 nm and a peak at 408 nm. The spectrum is attributed to the protonated form of an initially produced porphyrin anion radical. 4. Reduced porphyrin cytochrome c reacts with ferricytochrome c with a bimolecular constant of 2-10(5) M-1- S-1 in 2 mM phosphate pH 7.4, at 21 degrees C and of 2 - 10(6) M-1-S-1 under the same conditions but at 1 M ionic strength. It is proposed that electron transfer in an analogous exchange reaction between ferrocytochrome c and ferricytochrome c occurs via the exposed part of the haem.", "contents": "The reduction of porphyrin cytochrome c by hydrated electrons and the subsequent electron transfer reaction from reduced porphyrin cytochrome c to ferricytochrome c. 1. Hydrated electrons, produced by pulse radiolysis react with porphyrin cytochrome c with a bimolecular rate constant of 3-10(10) M-1 S-1 at 21 degrees C and pH 7.4. 2. After the reduction step an absorbance change with a half-life of 5 microns is observed with the spectral range of 430-470 nm. A relatively stable intermediate then decays with a half-life of 15 s. 3. The spectrum of the intermediate observed 50 microns after the generation of hydrated electrons shows a broad absorption band between 600 and 700 nm and a peak at 408 nm. The spectrum is attributed to the protonated form of an initially produced porphyrin anion radical. 4. Reduced porphyrin cytochrome c reacts with ferricytochrome c with a bimolecular constant of 2-10(5) M-1- S-1 in 2 mM phosphate pH 7.4, at 21 degrees C and of 2 - 10(6) M-1-S-1 under the same conditions but at 1 M ionic strength. It is proposed that electron transfer in an analogous exchange reaction between ferrocytochrome c and ferricytochrome c occurs via the exposed part of the haem."}
{"id": "PMID:192290", "title": "The effect of inhibitors on the oxygen kinetics of cytochrome c oxidase.", "content": "1. The oxygen kinetics of purified beef heart cytochrome c oxidase were investigated. 2. The effect of addition of various fixed concentrations of the inhibitors CO, HN3, HCOOH, HCN and H2S on the double reciprocal plot of respiration rate against oxygen concentration was studied. 3. CO is strictly competitive, azide and formate are uncompetitive, and cyanide and sulfide are non-competitive inhibitors towards oxygen. 4. Binding constants for the various inhibitors from secondary plots of the oxygen kinetics at pH 7.4 are: CO: Ki = 0.32 micronM, azide: Ki = 33 micronM; formate: Ki = 15 mM; cyanide: Ki = 0.2 micronM and sulfide: Ki = 0.2 micronM. 5. The possible significance of these results in the elucidation of the reaction mechanism is discussed.", "contents": "The effect of inhibitors on the oxygen kinetics of cytochrome c oxidase. 1. The oxygen kinetics of purified beef heart cytochrome c oxidase were investigated. 2. The effect of addition of various fixed concentrations of the inhibitors CO, HN3, HCOOH, HCN and H2S on the double reciprocal plot of respiration rate against oxygen concentration was studied. 3. CO is strictly competitive, azide and formate are uncompetitive, and cyanide and sulfide are non-competitive inhibitors towards oxygen. 4. Binding constants for the various inhibitors from secondary plots of the oxygen kinetics at pH 7.4 are: CO: Ki = 0.32 micronM, azide: Ki = 33 micronM; formate: Ki = 15 mM; cyanide: Ki = 0.2 micronM and sulfide: Ki = 0.2 micronM. 5. The possible significance of these results in the elucidation of the reaction mechanism is discussed."}
{"id": "PMID:192291", "title": "Activation of (Na+ + K+)-dependent ATPase by lipid vesicles of negative phospholipids.", "content": "1. Kidney (Na+ + K+)-stimulated ATPase was depleted of phospholipids by extraction with lubrol and inserted in lipid structures of known composition. Both ouabain-sensitive ATPase and phosphatase reactions could be partially restored by lipid replacement. 2. Lipid vesicles of natural and synthetic negative phospholipids proved to be effective. The low activity of uncharged liposomes was increased when negative charges were included into the bilayer structure. 3. Reactivation by negative phospholipids was accompanied by spontaneous re-assembly of a stable lipid-protein complex. By contrast, the interaction of lipid deficient ATPase complex with uncharged lamellae was possible only after sonication of lipid-protein suspension. Reactivation did not ensue. 4. The ouabain-sensitive ATPase reactivated by synthetic dioleoylphosphatidylglycerol yielded curvilinear Arrhenius plots. The same pattern was seen with the original undepleted microsomal preparation. A discontinuity close to the temperature of fluid-order transition was found with dimyristoyl phosphatidylglycerol. 5. It is concluded that reassembly of lipid-deficient (Na+ + K+)-stimulated ATPase requires the addition of diacylphospholipids with fluid acyl-chains and negatively charged polar heads able to assemble in an expanded lamellar configuration.", "contents": "Activation of (Na+ + K+)-dependent ATPase by lipid vesicles of negative phospholipids. 1. Kidney (Na+ + K+)-stimulated ATPase was depleted of phospholipids by extraction with lubrol and inserted in lipid structures of known composition. Both ouabain-sensitive ATPase and phosphatase reactions could be partially restored by lipid replacement. 2. Lipid vesicles of natural and synthetic negative phospholipids proved to be effective. The low activity of uncharged liposomes was increased when negative charges were included into the bilayer structure. 3. Reactivation by negative phospholipids was accompanied by spontaneous re-assembly of a stable lipid-protein complex. By contrast, the interaction of lipid deficient ATPase complex with uncharged lamellae was possible only after sonication of lipid-protein suspension. Reactivation did not ensue. 4. The ouabain-sensitive ATPase reactivated by synthetic dioleoylphosphatidylglycerol yielded curvilinear Arrhenius plots. The same pattern was seen with the original undepleted microsomal preparation. A discontinuity close to the temperature of fluid-order transition was found with dimyristoyl phosphatidylglycerol. 5. It is concluded that reassembly of lipid-deficient (Na+ + K+)-stimulated ATPase requires the addition of diacylphospholipids with fluid acyl-chains and negatively charged polar heads able to assemble in an expanded lamellar configuration."}
{"id": "PMID:192292", "title": "CMP-N-acetylneuraminic acid hydrolase, an ectoenzyme distributed unevenly over the hepatocyte surface.", "content": "The regional localization of CMP-N-acetylneuramic acid hydrolase at the hepatocyte surface was studied by using plasma membranes and hepatocytes isolated from rat liver. 1. By homogenization of the rat liver plasma membrane preparations and subsequent discontinuous sucrose gradient centrifugation, one light and two heavy membrane fractions were obtained. The origin of these three subfractions is discussed based on the specific activities in the three fractions of 5'-nucleotidase, alakaline phosphatase and Mg2+-ATPase and on electron microscopic examination of the fractions. Evidence is given suggesting that the light fraction is derived from the bile canalicular surface of the plasma membrane, and that the heavy fractions are derived predominantly from the sinusoidal and lateral surfaces of the liver cell membrane. CMP-AcNeu hydrolase was present at highest specific activity in one of the heavy subfractions. Therefore it is concluded that CMP-AcNeu hdyrolase is located preferentially in the sinusoidal and/or lateral plasma membrane parts of the liver cell. 2. Experiments with intact and disintegrated hepatocytes isolated from rat liver indicated that CMP-AcNeu hydrolase is located at the surface of the cell membrane, with its functional group directed to the outside.", "contents": "CMP-N-acetylneuraminic acid hydrolase, an ectoenzyme distributed unevenly over the hepatocyte surface. The regional localization of CMP-N-acetylneuramic acid hydrolase at the hepatocyte surface was studied by using plasma membranes and hepatocytes isolated from rat liver. 1. By homogenization of the rat liver plasma membrane preparations and subsequent discontinuous sucrose gradient centrifugation, one light and two heavy membrane fractions were obtained. The origin of these three subfractions is discussed based on the specific activities in the three fractions of 5'-nucleotidase, alakaline phosphatase and Mg2+-ATPase and on electron microscopic examination of the fractions. Evidence is given suggesting that the light fraction is derived from the bile canalicular surface of the plasma membrane, and that the heavy fractions are derived predominantly from the sinusoidal and lateral surfaces of the liver cell membrane. CMP-AcNeu hydrolase was present at highest specific activity in one of the heavy subfractions. Therefore it is concluded that CMP-AcNeu hdyrolase is located preferentially in the sinusoidal and/or lateral plasma membrane parts of the liver cell. 2. Experiments with intact and disintegrated hepatocytes isolated from rat liver indicated that CMP-AcNeu hydrolase is located at the surface of the cell membrane, with its functional group directed to the outside."}
{"id": "PMID:192293", "title": "Studies on spin-labelled egg lecithin dispersions.", "content": "ESR spectra of egg lecithin dispersions labelled with 5-nitroxide stearic acid are recorded with a 50 G field sweep, and also with a new technique which \"expands\" the spectrum by (1) recording pairs of adjoining peaks with a smaller field sweep and (2) superposing the common peaks. The expansion technique improves the precision of the order parameters determined from the hyperfine splitting measurements, and may prove useful in future spin label membrane studies. Approximate order parameters are derived to describe the fluidity of fatty acid spin-labelled membranes in those cases where either the inner or outer hyperfine extrema are not well defined. The ability of these expressions to measure the fluidity of labelled egg lecithin disperions for the temperature range 14-42 degrees C is examined.", "contents": "Studies on spin-labelled egg lecithin dispersions. ESR spectra of egg lecithin dispersions labelled with 5-nitroxide stearic acid are recorded with a 50 G field sweep, and also with a new technique which \"expands\" the spectrum by (1) recording pairs of adjoining peaks with a smaller field sweep and (2) superposing the common peaks. The expansion technique improves the precision of the order parameters determined from the hyperfine splitting measurements, and may prove useful in future spin label membrane studies. Approximate order parameters are derived to describe the fluidity of fatty acid spin-labelled membranes in those cases where either the inner or outer hyperfine extrema are not well defined. The ability of these expressions to measure the fluidity of labelled egg lecithin disperions for the temperature range 14-42 degrees C is examined."}
{"id": "PMID:192294", "title": "The intermediate monoclinic phase of phosphatidylcholines.", "content": "Two pure phospholipids, dimyristoyl phosphatidylcholine and dipalmitoyl phosphatidylcholine, have been studied using freeze-fracture electron microscopy and the partitioning of the spin label, TEMPO. It is found that the characteristic band pattern, corresponding to monoclinic symmetry in multilamellar liposomes, is observed only in freeze-fracture electron microphotographs when samples are quenched from temperatures intermediate between the chain melting transition temperature and the pretransition temperature of the membrane. Markings are also observed on fracture faces of samples quenched from below the pretransition, but these \"bands\" are few in number and are widely and irregularly spaced. The lipid membranes used for freeze-fracture were prepared using detergent dialysis and are thought to consist of one, two, or some small number of concentric bilayer shells. These observations are in excellent accord with the recent, prior studies of Janiak, M.J., Small, D.M. and Shirley, G.G., ((1976) Biochemistry 15, 4575--4580), who found monoclinic symmetry (Pbeta' structure) in multilamellar liposomes of these phospholipids only when the sample temperature was intermediate between the main, chain melting transition temperature, and the pretransition temperature. The significance of these results for relating freeze-fracture electron microphotographis to phase diagrams derived from spin label or calorimetric data is discussed briefly. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) partitioning data show distinct differences between liposomal preparations of these lipids, and other preparations having fewer bilayers per vesicular structure, with respect to the position, width, and hysteresis of the pretransition.", "contents": "The intermediate monoclinic phase of phosphatidylcholines. Two pure phospholipids, dimyristoyl phosphatidylcholine and dipalmitoyl phosphatidylcholine, have been studied using freeze-fracture electron microscopy and the partitioning of the spin label, TEMPO. It is found that the characteristic band pattern, corresponding to monoclinic symmetry in multilamellar liposomes, is observed only in freeze-fracture electron microphotographs when samples are quenched from temperatures intermediate between the chain melting transition temperature and the pretransition temperature of the membrane. Markings are also observed on fracture faces of samples quenched from below the pretransition, but these \"bands\" are few in number and are widely and irregularly spaced. The lipid membranes used for freeze-fracture were prepared using detergent dialysis and are thought to consist of one, two, or some small number of concentric bilayer shells. These observations are in excellent accord with the recent, prior studies of Janiak, M.J., Small, D.M. and Shirley, G.G., ((1976) Biochemistry 15, 4575--4580), who found monoclinic symmetry (Pbeta' structure) in multilamellar liposomes of these phospholipids only when the sample temperature was intermediate between the main, chain melting transition temperature, and the pretransition temperature. The significance of these results for relating freeze-fracture electron microphotographis to phase diagrams derived from spin label or calorimetric data is discussed briefly. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) partitioning data show distinct differences between liposomal preparations of these lipids, and other preparations having fewer bilayers per vesicular structure, with respect to the position, width, and hysteresis of the pretransition."}
{"id": "PMID:192295", "title": "Stimulation of calcium uptake in platelet membrane vesicles by adenosine 3',5'-cyclic monophosphate and protein kinase.", "content": "The events involved in platelet shape change, aggregation, the release reaction and contraction are thought to be mediated by the availability of Ca2+. Increased cytoplasmic calcium, released from intracellular stores, triggers platelet activity, and increased concentration of adenosine 3',5'-cyclic monophosphate (cyclic AMP) inhibits platelet alterations. We have studied the hypothesis that cyclic AMP may regulate the level of platelet cytoplasmic calcium by stimulating calcium removal by a membrane system. Such a hypothesis would be consistent with the reversibility of most manifestations of platelet activation. Human platelets were sonicated and unlysed platelets, mitochondria and granules were removed by centrifugation at 19 000 X g. Electron microscopy shows that the sediment, after centrifugation of the supernatant at 40 000 X g consists to a large extent of membrane vesicles. Such preparations actively concentrate calcium, as measured by the uptake of 45Ca, and also have the maximal calcium-stimulated ATPase activity. Optimal calcium uptake requires ATP and oxalate, and release of calcium from loaded vesicles was stimulated by the calcium ionophore A23187 and inhibited by LaCl3. These data indicate that calcium was being actively concentrated within membrane vesicles. After washing of such preparations in the absence of ATP, their capacity to take up Ca2+ is reduced to an initial value of 2.8 nmol/mg protein per min. In the presence of 2 - 10(6) M cyclic AMP to which was added a protein kinase preparation from human platelets, up to a 3-fold increase of this rate of uptake was observed. These results suggest that in platelets, as in muscle, cyclic AMP is a regulatory factor in the control of cytoplasmic calcium. Although the cyclic nucleotide may have still other functions, it appears likely that the well-known inhibition of many platelet activities by high intracellular cyclic AMP concentrations is directly linked to the stimulation of the removal of Ca2+ from the cytoplasm.", "contents": "Stimulation of calcium uptake in platelet membrane vesicles by adenosine 3',5'-cyclic monophosphate and protein kinase. The events involved in platelet shape change, aggregation, the release reaction and contraction are thought to be mediated by the availability of Ca2+. Increased cytoplasmic calcium, released from intracellular stores, triggers platelet activity, and increased concentration of adenosine 3',5'-cyclic monophosphate (cyclic AMP) inhibits platelet alterations. We have studied the hypothesis that cyclic AMP may regulate the level of platelet cytoplasmic calcium by stimulating calcium removal by a membrane system. Such a hypothesis would be consistent with the reversibility of most manifestations of platelet activation. Human platelets were sonicated and unlysed platelets, mitochondria and granules were removed by centrifugation at 19 000 X g. Electron microscopy shows that the sediment, after centrifugation of the supernatant at 40 000 X g consists to a large extent of membrane vesicles. Such preparations actively concentrate calcium, as measured by the uptake of 45Ca, and also have the maximal calcium-stimulated ATPase activity. Optimal calcium uptake requires ATP and oxalate, and release of calcium from loaded vesicles was stimulated by the calcium ionophore A23187 and inhibited by LaCl3. These data indicate that calcium was being actively concentrated within membrane vesicles. After washing of such preparations in the absence of ATP, their capacity to take up Ca2+ is reduced to an initial value of 2.8 nmol/mg protein per min. In the presence of 2 - 10(6) M cyclic AMP to which was added a protein kinase preparation from human platelets, up to a 3-fold increase of this rate of uptake was observed. These results suggest that in platelets, as in muscle, cyclic AMP is a regulatory factor in the control of cytoplasmic calcium. Although the cyclic nucleotide may have still other functions, it appears likely that the well-known inhibition of many platelet activities by high intracellular cyclic AMP concentrations is directly linked to the stimulation of the removal of Ca2+ from the cytoplasm."}
{"id": "PMID:192296", "title": "Further studies of the action of methionyl adenylate on chick embryo fibroblasts.", "content": "Methionyl adenylate (Met-AMP) inhibits protein synthesis by interacting with methionyl-tRNA synthetase. Addition of 1--3 mM inhibitor to chick embryo fibroblasts rapidly stops protein synthesis and DNA synthesis but not RNA synthesis. These effects can be reversed by renewal of the medium. The extent and reversibility of protein and DNA syntheses depend on the concentration of MetAMP in the cultures, the length of exposure and the cellular density. MetAMP is recognised by several enzymes as substrate and/or as inhibitor. MetAmp is degraded to methionol plus 5'-adenylic acid by 5'-phosphodiesterase. Adenosine deaminase, adenylic acid deaminase and 3':5'-phosphodiesterase cannot use MetAMP as substrate but the last enzyme is inhibited. The presence of MetAMP in cultures provokes a small but reproducible increase in the level of methionyl-tRNA synthetase and 5'-phosphodiesterase.", "contents": "Further studies of the action of methionyl adenylate on chick embryo fibroblasts. Methionyl adenylate (Met-AMP) inhibits protein synthesis by interacting with methionyl-tRNA synthetase. Addition of 1--3 mM inhibitor to chick embryo fibroblasts rapidly stops protein synthesis and DNA synthesis but not RNA synthesis. These effects can be reversed by renewal of the medium. The extent and reversibility of protein and DNA syntheses depend on the concentration of MetAMP in the cultures, the length of exposure and the cellular density. MetAMP is recognised by several enzymes as substrate and/or as inhibitor. MetAmp is degraded to methionol plus 5'-adenylic acid by 5'-phosphodiesterase. Adenosine deaminase, adenylic acid deaminase and 3':5'-phosphodiesterase cannot use MetAMP as substrate but the last enzyme is inhibited. The presence of MetAMP in cultures provokes a small but reproducible increase in the level of methionyl-tRNA synthetase and 5'-phosphodiesterase."}
{"id": "PMID:192297", "title": "DNA synthesis in detergent-treated mouse ascites sarcoma cells.", "content": "Mouse ascites sarcoma cells (SR-C3H/He cells) were made  permeable to nucleoside triphosphates by treatment with nonionic detergents in a nearly isotonic condition. The permeable cells synthesized DNA in the presence of the four deoxyribonucleoside triphosphates, ATP, Mg2+, and the proper ionic environment. The optimum detergent concentration for DNA synthesis was 0.015--0.020% with Triton X-100, 0.020% with Nonidet P-40, and about 0.0025% with Brij 58. Higher concentrations of detergents were rather inhibitory to DNA synthesis. DNA synthesis in Triton-permeabilized cells was thought to be replicative, and the activity in the optimum conditions was much higher than that measured in hypotonic permeable cells or in isolated nuclei. These studies show the potential usefulness of detergent treatment for examining DNA replication in mammalian cells in vitro.", "contents": "DNA synthesis in detergent-treated mouse ascites sarcoma cells. Mouse ascites sarcoma cells (SR-C3H/He cells) were made  permeable to nucleoside triphosphates by treatment with nonionic detergents in a nearly isotonic condition. The permeable cells synthesized DNA in the presence of the four deoxyribonucleoside triphosphates, ATP, Mg2+, and the proper ionic environment. The optimum detergent concentration for DNA synthesis was 0.015--0.020% with Triton X-100, 0.020% with Nonidet P-40, and about 0.0025% with Brij 58. Higher concentrations of detergents were rather inhibitory to DNA synthesis. DNA synthesis in Triton-permeabilized cells was thought to be replicative, and the activity in the optimum conditions was much higher than that measured in hypotonic permeable cells or in isolated nuclei. These studies show the potential usefulness of detergent treatment for examining DNA replication in mammalian cells in vitro."}
{"id": "PMID:192298", "title": "Resolution and general properties of different types of ribosomal protein kinases in mouse plasmocytoma.", "content": "Three different types of protein kinases (ATP: protein phosphotransferase, EC 2.7.1.37) were isolated and partially purified from a mouse plasmacytoma microsomal KCl wash fraction, then chromatographed on DEAE cellulose and phosphocellulose. The three protein kinase activities designated by protein kinase I, II and III were characterized with respect to their capacity to utilize [gamma-32P]ATP and [gamma-32P]GTP, to interact with cyclic AMP, stimulation by cyclic AMP, substrate specificity and sedimentation behaviour on glycerol gradient centrifugation. Protein kinase I was found to be cyclic AMP dependent and preferentially phosphorylated histones. Protein kinase II and III were insensitive to cyclic AMP, protein kinase II preferentially phosphorylated histones and the protein(s) of a ribosomal KCl wash fraction eluted from DEAE cellulose between 0.2 and 0.35 M KCl and termed \"PPx\". Protein kinase III phosphorylated casein and ribosomal proteins to a great extent. Studies with glycerol density gradient centrifugation indicated that protein kinase I sediments as a component of about 4.4 S, protein kinase II of 4.3 S and protein kinase III of 3 S. Chromatography on phosphocellulose of the protein kinases isolated from purified free polysomes showed the same type of protein kinases as those from microsomes. So it appears unlikely that protein kinase I and II were contaminants from the cytosol.", "contents": "Resolution and general properties of different types of ribosomal protein kinases in mouse plasmocytoma. Three different types of protein kinases (ATP: protein phosphotransferase, EC 2.7.1.37) were isolated and partially purified from a mouse plasmacytoma microsomal KCl wash fraction, then chromatographed on DEAE cellulose and phosphocellulose. The three protein kinase activities designated by protein kinase I, II and III were characterized with respect to their capacity to utilize [gamma-32P]ATP and [gamma-32P]GTP, to interact with cyclic AMP, stimulation by cyclic AMP, substrate specificity and sedimentation behaviour on glycerol gradient centrifugation. Protein kinase I was found to be cyclic AMP dependent and preferentially phosphorylated histones. Protein kinase II and III were insensitive to cyclic AMP, protein kinase II preferentially phosphorylated histones and the protein(s) of a ribosomal KCl wash fraction eluted from DEAE cellulose between 0.2 and 0.35 M KCl and termed \"PPx\". Protein kinase III phosphorylated casein and ribosomal proteins to a great extent. Studies with glycerol density gradient centrifugation indicated that protein kinase I sediments as a component of about 4.4 S, protein kinase II of 4.3 S and protein kinase III of 3 S. Chromatography on phosphocellulose of the protein kinases isolated from purified free polysomes showed the same type of protein kinases as those from microsomes. So it appears unlikely that protein kinase I and II were contaminants from the cytosol."}
{"id": "PMID:192299", "title": "Arylamidases of rat liver and chemically induced hepatomas. II. Preparation and characterization of monospecific antisera against two distinct arylamidase-active antigens.", "content": "Monospecific antisera were prepared against the most prominent arylamidase (alpha-aminoacyl-peptide hydrolase (microsomal), EC 3.4.11.2) active antigen in plasma membranes (the plasma membrane arylamidase) and lysomal content (the lysosomal content arylamidase), respectively. Plasma membrane extract and lysosomal content were allowed to react in crossed immunoelectrophoresis against their homologous antisera. The electrophoretic plates were washed extensively, dried and subsequently stained for arylamidase activity. The particular immunoprecipitates were thus identified and could be excised to be used for immunizations. The two resulting antisera precipitated the arylamidase used for immunization, but failed to be monospecific as they precipitated additional antigens. These antisera with restricted specificity against some plasma membrane and lysosomal content antigens, respectively, were used to produce immunoprecipitates intended for new attempts to prepare monospecific antisera by a second cycle of immunizations. A monospecific antiserum against the plasma membrane arylamidase was thus obtained, while a third cycle of immunizations was needed to get a monospecific anti-lysosomal content antiserum. The plasma membrane arylamidase showed ATPase activity also after precipitation with the monospecific antiserum, thus still retaining its characteristics as a multienzyme complex.", "contents": "Arylamidases of rat liver and chemically induced hepatomas. II. Preparation and characterization of monospecific antisera against two distinct arylamidase-active antigens. Monospecific antisera were prepared against the most prominent arylamidase (alpha-aminoacyl-peptide hydrolase (microsomal), EC 3.4.11.2) active antigen in plasma membranes (the plasma membrane arylamidase) and lysomal content (the lysosomal content arylamidase), respectively. Plasma membrane extract and lysosomal content were allowed to react in crossed immunoelectrophoresis against their homologous antisera. The electrophoretic plates were washed extensively, dried and subsequently stained for arylamidase activity. The particular immunoprecipitates were thus identified and could be excised to be used for immunizations. The two resulting antisera precipitated the arylamidase used for immunization, but failed to be monospecific as they precipitated additional antigens. These antisera with restricted specificity against some plasma membrane and lysosomal content antigens, respectively, were used to produce immunoprecipitates intended for new attempts to prepare monospecific antisera by a second cycle of immunizations. A monospecific antiserum against the plasma membrane arylamidase was thus obtained, while a third cycle of immunizations was needed to get a monospecific anti-lysosomal content antiserum. The plasma membrane arylamidase showed ATPase activity also after precipitation with the monospecific antiserum, thus still retaining its characteristics as a multienzyme complex."}
{"id": "PMID:192300", "title": "Triacylglycerol and very low density lipoprotein secretion into plasma of squirrel monkeys.", "content": "We determined the effects of varying the types and level of dietary fat and cholesterol on the increase in plasma total triacylglycerol concentrations after injection of Triton WR-1339, an inhibitor of lipoprotein lipase, into monkeys that had been subjected to an overnight fast. The monkeys that had been treated with Triton WR-1339 were then given a test meal by intragastric intubation. Dietary cholesterol, high levels of fat and saturated fat in the habitual diet reduced the rate of release of triacylglycerol to plasma in the fasted monkey. We also determined the changes in protein and lipid concentrations of the different lipoprotein fractions. The injection of Triton WR-1339 resulted in a linear increase with time in the concentration of protein and triacylglycerol in the very low density (chylomicron-free and d less than 1.006) lipoproteins, but there was an increase in the ratio of traicylglycerol to protein in that fraction. Most of the increase (96%) in very low density protein was in the B protein. Regardless of the habitual diet, a test meal accentuated the rate of triacylglycerol appearance in whole plasma and in the very low density lipoproteins of Triton WR-1339-treated monkeys, and the rate of increase of the protein component after feeding was slightly higher. Thus the administration of a meal to the fasted Triton WR-1339-treated squirrel monkey further increased the proportion of triacylglycerol in very low density lipoproteins. Although dietary cholesterol and saturated fat in the habitual diet depressed the rate of increase in very low density triacylglycerol during fasting, the rate of protein synthesis was not significantly affected. After administration of a test meal the rates of increase in triacylglycerol and protein in the very low density lipoproteins were similar for monkeys from the different diet groups. Triton WR-1339 administration caused a slight and progressive increase in the intermediate density (d 1.006-1.019) lipoproteins and a marked and progressive decrease in the low density (d 1.019-1.063) lipoproteins. There was an immediate (by 5 min) drop of 70% or more in high density (d 1.063-1.21) lipoprotein protein, but the lipids except triacylglycerol remained unchanged. There was a decrease in both the A (the major fraction) and C proteins. The rates of very low density B protein secretion were comparable to the rates of low density lipoprotein catabolism that had been previously demonstrated for this species.", "contents": "Triacylglycerol and very low density lipoprotein secretion into plasma of squirrel monkeys. We determined the effects of varying the types and level of dietary fat and cholesterol on the increase in plasma total triacylglycerol concentrations after injection of Triton WR-1339, an inhibitor of lipoprotein lipase, into monkeys that had been subjected to an overnight fast. The monkeys that had been treated with Triton WR-1339 were then given a test meal by intragastric intubation. Dietary cholesterol, high levels of fat and saturated fat in the habitual diet reduced the rate of release of triacylglycerol to plasma in the fasted monkey. We also determined the changes in protein and lipid concentrations of the different lipoprotein fractions. The injection of Triton WR-1339 resulted in a linear increase with time in the concentration of protein and triacylglycerol in the very low density (chylomicron-free and d less than 1.006) lipoproteins, but there was an increase in the ratio of traicylglycerol to protein in that fraction. Most of the increase (96%) in very low density protein was in the B protein. Regardless of the habitual diet, a test meal accentuated the rate of triacylglycerol appearance in whole plasma and in the very low density lipoproteins of Triton WR-1339-treated monkeys, and the rate of increase of the protein component after feeding was slightly higher. Thus the administration of a meal to the fasted Triton WR-1339-treated squirrel monkey further increased the proportion of triacylglycerol in very low density lipoproteins. Although dietary cholesterol and saturated fat in the habitual diet depressed the rate of increase in very low density triacylglycerol during fasting, the rate of protein synthesis was not significantly affected. After administration of a test meal the rates of increase in triacylglycerol and protein in the very low density lipoproteins were similar for monkeys from the different diet groups. Triton WR-1339 administration caused a slight and progressive increase in the intermediate density (d 1.006-1.019) lipoproteins and a marked and progressive decrease in the low density (d 1.019-1.063) lipoproteins. There was an immediate (by 5 min) drop of 70% or more in high density (d 1.063-1.21) lipoprotein protein, but the lipids except triacylglycerol remained unchanged. There was a decrease in both the A (the major fraction) and C proteins. The rates of very low density B protein secretion were comparable to the rates of low density lipoprotein catabolism that had been previously demonstrated for this species."}
{"id": "PMID:192301", "title": "Branched blood group A-active fucolipids of hog gastric mucosa.", "content": "New complex glycolipids have been extracted from hog gastric mucosa with the mixture of 0.4 M sodium acetate in methanol/chloroform/water. Three A-active fucolipids having branched carbohydrate chains have been purified from this extract. The postulated structures of these glycolipids are based on the results of partial acid hydrolysis, oxidation with periodate and chromium trioxide, and permethylation studies.", "contents": "Branched blood group A-active fucolipids of hog gastric mucosa. New complex glycolipids have been extracted from hog gastric mucosa with the mixture of 0.4 M sodium acetate in methanol/chloroform/water. Three A-active fucolipids having branched carbohydrate chains have been purified from this extract. The postulated structures of these glycolipids are based on the results of partial acid hydrolysis, oxidation with periodate and chromium trioxide, and permethylation studies."}
{"id": "PMID:192302", "title": "High density lipoprotein and low density lipoprotein catabolism by human liver and parenchymal and non-parenchymal cells from rat liver.", "content": "The capacity of the homogenates from human liver, rat parenchymal cells, rat non-parenchymal cells and total rat liver for the breakdown of human and rat high density lipoprotein (HDL) and human low density lipoprotein (LDL) was determined. Human HDL was catabolized by human liver, in contrast to human LDL, the protein degradation of which was low or absent. Human and rat HDL were catabolized by both the rat parenchymal and non-parenchymal cell homogenates with, on protein base, a 10-times higher activity in the non-parenchymal liver cells. This implies that more than 50% of the total liver capacity for HDL protein degradation is localized in these cell types. Human LDL degradation in the rat could only be detected in the non-parenchymal cell homogenates. These findings are discussed in view of the function of HDL and LDL as carriers for cholesterol.", "contents": "High density lipoprotein and low density lipoprotein catabolism by human liver and parenchymal and non-parenchymal cells from rat liver. The capacity of the homogenates from human liver, rat parenchymal cells, rat non-parenchymal cells and total rat liver for the breakdown of human and rat high density lipoprotein (HDL) and human low density lipoprotein (LDL) was determined. Human HDL was catabolized by human liver, in contrast to human LDL, the protein degradation of which was low or absent. Human and rat HDL were catabolized by both the rat parenchymal and non-parenchymal cell homogenates with, on protein base, a 10-times higher activity in the non-parenchymal liver cells. This implies that more than 50% of the total liver capacity for HDL protein degradation is localized in these cell types. Human LDL degradation in the rat could only be detected in the non-parenchymal cell homogenates. These findings are discussed in view of the function of HDL and LDL as carriers for cholesterol."}
{"id": "PMID:192303", "title": "Uptake and degradation of cholesterol ester-labelled rat plasma lipoproteins in purified rat hepatocytes and nonparenchymal liver cells.", "content": "1. A new method for isolation and purification of rat liver hepatocytes and nonparenchymal cells by differential centrifugation is described. 2. Cholesterol ester-labelled lipoproteins (prepared by the action of lecithin: cholesterol acyltransferase) intravenously injected were taken up by hepatocytes and nonparenchymal cells. 3. Hepatocytes and nonparenchymal cells in suspension were able to take up and hydrolyse the cholesterol ester portion of lipoproteins. 4. Uptake of cholesterol ester labelled whole rat plasma and high density lipoproteins (HDL) increased with increasing concentrations until a distinct saturation level was reached in hepatocytes. In nonparenchymal cells there was no saturation of lipoprotein uptake. 5. Concanavalin A inhibited cholesterol ester-labelled lipoprotein uptake in hepatocytes, indicating that the uptake at least partially depends on carbohydrate sites on the cell surface. The uptake in nonparenchymal cells was unaffected of concanavalin A. 6. The specific activity of the acid cholesterol ester hydrolase was the same in homogenates from hepatocytes and nonparenchymal cells while acyl-CoA: cholesterol acyltransferase was found almost exclusively in hepatocytes.", "contents": "Uptake and degradation of cholesterol ester-labelled rat plasma lipoproteins in purified rat hepatocytes and nonparenchymal liver cells. 1. A new method for isolation and purification of rat liver hepatocytes and nonparenchymal cells by differential centrifugation is described. 2. Cholesterol ester-labelled lipoproteins (prepared by the action of lecithin: cholesterol acyltransferase) intravenously injected were taken up by hepatocytes and nonparenchymal cells. 3. Hepatocytes and nonparenchymal cells in suspension were able to take up and hydrolyse the cholesterol ester portion of lipoproteins. 4. Uptake of cholesterol ester labelled whole rat plasma and high density lipoproteins (HDL) increased with increasing concentrations until a distinct saturation level was reached in hepatocytes. In nonparenchymal cells there was no saturation of lipoprotein uptake. 5. Concanavalin A inhibited cholesterol ester-labelled lipoprotein uptake in hepatocytes, indicating that the uptake at least partially depends on carbohydrate sites on the cell surface. The uptake in nonparenchymal cells was unaffected of concanavalin A. 6. The specific activity of the acid cholesterol ester hydrolase was the same in homogenates from hepatocytes and nonparenchymal cells while acyl-CoA: cholesterol acyltransferase was found almost exclusively in hepatocytes."}
{"id": "PMID:192304", "title": "Thermal behavior of human plasma high density lipoprotein.", "content": "Human plasma low density lipoprotein displays a reversible thermal transition between 20 and 40 degrees C, due to a phase transition of its core cholesterol ester from a smectic to a more liquid-like state. To determine if the cholesterol of high density lipoprotein (HDL) displays similar thermal behavior, the human lipoprotein and its extracted lipid have been examined by differential scanning calorimetry, low angle X-ray scattering and polarizing microscopy. Neither HDL2**(d 1.063--1.125--1.21 g/ml) nor HDL3(d1.125--1.21g/ml) show thermal transitions between O and 60 degrees C. By contrast cholesterol ester isolated from HDL and mixtures of cholesterol oleate and linoleate show reversible liquid crystalline transitions between 20 and 40 degreesC. X-ray scattering studies of HDL2 and HDL3 performed at 10 degreesC show no scattering fringes attributable to a smectic phase of cholesterol ester. When HDL is heated to temperatures above 60 degreesC a broad, double-peaked endotherm is observed. The first component (peak temperature=71 degreesC) corresponds to a selective release of apoprotein A-1 from the lipoprotein, and the second component (peak temperature=90 degreesC) to a more generalized disruption of lipoprotein structure with release of cholesterol ester and apoprotein A-2. Following the thermal disruption of HDL, reversible liquid crystalline transitions of cholesterol ester can be seen by differential scanning calorimetry and polarizing microscopy, showing the presence of large domains of cholesterol ester. The absence of cholesterol ester transitions in intact HDL may indicate an interaction of cholesterol ester molecules with the protein-phospholipid surface of HDL that prevents the formation of an organized lipid phase. The high temperature behavior of HDL indicates that apoprotein A-1 is less important than apoprotein A-2 in maintaining the HDL apolar lipids in the form of a stable miroemulsion.", "contents": "Thermal behavior of human plasma high density lipoprotein. Human plasma low density lipoprotein displays a reversible thermal transition between 20 and 40 degrees C, due to a phase transition of its core cholesterol ester from a smectic to a more liquid-like state. To determine if the cholesterol of high density lipoprotein (HDL) displays similar thermal behavior, the human lipoprotein and its extracted lipid have been examined by differential scanning calorimetry, low angle X-ray scattering and polarizing microscopy. Neither HDL2**(d 1.063--1.125--1.21 g/ml) nor HDL3(d1.125--1.21g/ml) show thermal transitions between O and 60 degrees C. By contrast cholesterol ester isolated from HDL and mixtures of cholesterol oleate and linoleate show reversible liquid crystalline transitions between 20 and 40 degreesC. X-ray scattering studies of HDL2 and HDL3 performed at 10 degreesC show no scattering fringes attributable to a smectic phase of cholesterol ester. When HDL is heated to temperatures above 60 degreesC a broad, double-peaked endotherm is observed. The first component (peak temperature=71 degreesC) corresponds to a selective release of apoprotein A-1 from the lipoprotein, and the second component (peak temperature=90 degreesC) to a more generalized disruption of lipoprotein structure with release of cholesterol ester and apoprotein A-2. Following the thermal disruption of HDL, reversible liquid crystalline transitions of cholesterol ester can be seen by differential scanning calorimetry and polarizing microscopy, showing the presence of large domains of cholesterol ester. The absence of cholesterol ester transitions in intact HDL may indicate an interaction of cholesterol ester molecules with the protein-phospholipid surface of HDL that prevents the formation of an organized lipid phase. The high temperature behavior of HDL indicates that apoprotein A-1 is less important than apoprotein A-2 in maintaining the HDL apolar lipids in the form of a stable miroemulsion."}
{"id": "PMID:192305", "title": "Odd-and even-numbered fatty acids. Their contrasting behavior in normal and fowlpox virus-infected epithelium.", "content": "Upon infection with fowlpox virus, the amount of odd-numbered fatty acids in chick scalp epithelium shows a significant decrease compared with control values. This effect begins quite early and progresses throughout the period of infection. Individual members of the odd-numbered family (C15--C27 inclusive) were quantitatively related to the group as a whole during most of the infection. Experiments involving the administration of labeled acetate in vivo demonstrated an increase in the synthesis of even-numbered fatty acids and a decrease in the synthesis of odd-numbered fatty acids in infected epithelium. The reduced synthesis of odd-numbered fatty acids in infected epithelium could also be demonstrated with labeled propionate. The influence of the alpha-oxidation pathway was assayed in chick scalp epithelium in vivo by the administration of [1-14C,9,10-3H] stearic acid. The C17 acids formed had a 3H/14C ratio similar to that of the C16 acids, indicating that most label incorporation into C17 was due to beta-oxidation to acetate followed by resynthesis into fatty acids. C17 fatty acids from control and infected epithelium had similar 3H/14C ratios, indicating that the alpha-oxidation pathway probably does not contribute to the differences in odd-numbered fatty acid content observed. In assays for fatty acid synthetase activty, both [14C] acetyl-CoA and [14C]-propionyl-CoA were used as initial acceptors. The specific activities of preparations from infected scalp were similar to those of control preparations with both substrates. These results suggest that there is no decline in the ability to utilize propionate for fatty acid synthesis in infected epithelium.", "contents": "Odd-and even-numbered fatty acids. Their contrasting behavior in normal and fowlpox virus-infected epithelium. Upon infection with fowlpox virus, the amount of odd-numbered fatty acids in chick scalp epithelium shows a significant decrease compared with control values. This effect begins quite early and progresses throughout the period of infection. Individual members of the odd-numbered family (C15--C27 inclusive) were quantitatively related to the group as a whole during most of the infection. Experiments involving the administration of labeled acetate in vivo demonstrated an increase in the synthesis of even-numbered fatty acids and a decrease in the synthesis of odd-numbered fatty acids in infected epithelium. The reduced synthesis of odd-numbered fatty acids in infected epithelium could also be demonstrated with labeled propionate. The influence of the alpha-oxidation pathway was assayed in chick scalp epithelium in vivo by the administration of [1-14C,9,10-3H] stearic acid. The C17 acids formed had a 3H/14C ratio similar to that of the C16 acids, indicating that most label incorporation into C17 was due to beta-oxidation to acetate followed by resynthesis into fatty acids. C17 fatty acids from control and infected epithelium had similar 3H/14C ratios, indicating that the alpha-oxidation pathway probably does not contribute to the differences in odd-numbered fatty acid content observed. In assays for fatty acid synthetase activty, both [14C] acetyl-CoA and [14C]-propionyl-CoA were used as initial acceptors. The specific activities of preparations from infected scalp were similar to those of control preparations with both substrates. These results suggest that there is no decline in the ability to utilize propionate for fatty acid synthesis in infected epithelium."}
{"id": "PMID:192307", "title": "1H NMR studies of the heme iron coordination in cytochrome c-552 from Euglena gracilis.", "content": "The coordination of the heme iron in cytochrome c-552 from Euglena gracilis was investigated by 1H NMR studies at 360 MHz. The data imply that the axial heme ligands are His-14 and Met-56 in both the oxidized and the reduced protein. Studies of mixed solutions of ferro- and ferricytochrome c-552, which provided much of the information on the heme structure, also showed that the intermolecular electron exchange is characterized by a bimolecular rate constant of 5-10(6) mol-1-s-1 at 29 degrees C, which is three orders of magnitude faster than the corresponding reaction in solutions of mammalian cytochromes c.", "contents": "1H NMR studies of the heme iron coordination in cytochrome c-552 from Euglena gracilis. The coordination of the heme iron in cytochrome c-552 from Euglena gracilis was investigated by 1H NMR studies at 360 MHz. The data imply that the axial heme ligands are His-14 and Met-56 in both the oxidized and the reduced protein. Studies of mixed solutions of ferro- and ferricytochrome c-552, which provided much of the information on the heme structure, also showed that the intermolecular electron exchange is characterized by a bimolecular rate constant of 5-10(6) mol-1-s-1 at 29 degrees C, which is three orders of magnitude faster than the corresponding reaction in solutions of mammalian cytochromes c."}
{"id": "PMID:192308", "title": "1H NMR studies at 360 MHz of the aromatic amino acid residues in ferrocytochrome c-552 from Euglena gracilis.", "content": "The resonances of the aromatic rings in the 1H NMR spectra at 360 MHz of ferrocytochrome c-552 of Euglena gracilis were investigated by double resonance techniques. The spin systems of the two tryptophan and four of the tyrosine residues could be identified. This analysis of the aromatic region of the 1H NMR spectrum provided evidence that His-14 is bound to the heme iron. It gave also some insight into the molecular dynamics of ferrocytochrome c-552 in that it showed that of the six aromatic rings, four tyrosines were rotating rapidly about the Cbeta-Cgamma bond, while one tyrosine and the single phenylalanine were restricted in their rotational mobilities by their environmnent in the protein.", "contents": "1H NMR studies at 360 MHz of the aromatic amino acid residues in ferrocytochrome c-552 from Euglena gracilis. The resonances of the aromatic rings in the 1H NMR spectra at 360 MHz of ferrocytochrome c-552 of Euglena gracilis were investigated by double resonance techniques. The spin systems of the two tryptophan and four of the tyrosine residues could be identified. This analysis of the aromatic region of the 1H NMR spectrum provided evidence that His-14 is bound to the heme iron. It gave also some insight into the molecular dynamics of ferrocytochrome c-552 in that it showed that of the six aromatic rings, four tyrosines were rotating rapidly about the Cbeta-Cgamma bond, while one tyrosine and the single phenylalanine were restricted in their rotational mobilities by their environmnent in the protein."}
{"id": "PMID:192309", "title": "Study of steroid-proteininteractions by electron spin resonance spectroscopy. Binding of a spin-labelled dihydrotestosterone to bovine serum albumin.", "content": "The interaction of bovine serum albumin with dihydrotestosterone bearing a spin label at C-3 was studied using electron spin resonance (ESR) spectroscopy. Quantitative binding parameters (Ka approximately 10(5) M-1; maximum binding capacity; two sites/mol albumin) obtained by ESR were in good agreement with those given by equilibrium dialysis. ESR study at various temperatures allowed the calculation of the thermodynamic parameters of the steroid-protein interaction: deltaG=-6.8 kcal/mol; deltaH=-7.9 kcal/mol; deltaS=-3.2 cal/mol per degree and confirmed a transition temperature of about 65 degrees C for albumin. Na, Liland Ca salts had a generally favorable effect on the interaction whereas other ions (e.g. Hg, Cu) impaired the binding process. Study of the width of the ESR spectra of the protein-bound spin-labelled steroid and extrapolation of a 2 T value to infinite viscosity (Azz coupling constant) indicated a non-polar binding site, which became increasingly hydrophobic as the temperature was raised. Since this methodology can give both pertinent quantitative and qualitative data, ESR spectroscopy should be of value in the study of steroid-protein interactions of biological significance.", "contents": "Study of steroid-proteininteractions by electron spin resonance spectroscopy. Binding of a spin-labelled dihydrotestosterone to bovine serum albumin. The interaction of bovine serum albumin with dihydrotestosterone bearing a spin label at C-3 was studied using electron spin resonance (ESR) spectroscopy. Quantitative binding parameters (Ka approximately 10(5) M-1; maximum binding capacity; two sites/mol albumin) obtained by ESR were in good agreement with those given by equilibrium dialysis. ESR study at various temperatures allowed the calculation of the thermodynamic parameters of the steroid-protein interaction: deltaG=-6.8 kcal/mol; deltaH=-7.9 kcal/mol; deltaS=-3.2 cal/mol per degree and confirmed a transition temperature of about 65 degrees C for albumin. Na, Liland Ca salts had a generally favorable effect on the interaction whereas other ions (e.g. Hg, Cu) impaired the binding process. Study of the width of the ESR spectra of the protein-bound spin-labelled steroid and extrapolation of a 2 T value to infinite viscosity (Azz coupling constant) indicated a non-polar binding site, which became increasingly hydrophobic as the temperature was raised. Since this methodology can give both pertinent quantitative and qualitative data, ESR spectroscopy should be of value in the study of steroid-protein interactions of biological significance."}
{"id": "PMID:192310", "title": "Arylamidases of rat liver and chemically induced hepatomas. 1. Subcellular distribution of L-leucine. 2. Naphthylamidase-active antigens.", "content": "The subcellular distribution of arylamidase-active antigens in rat liver and in two chemically induced hepatomas (D23 and D33) was investigated. Soluble antigens or detergent-solubilized membrane antigens from isolated subcellular fractions were tested in fused rocket immunoelectrophoresis against antisera prepared against each of the fractions. The arylamidase active antigens were identified by means of a zymogram technique using L-leucine 2-naphthylamide as substrate. Two arylamidase-active antigens were shown to be shared between plasma membranes, microsomes, lysosomal membranes and lysosomal content of the hepatocytes. One of these occurred predominantly in the plasma membranes (the plasma membrane arylamidase) while the other was preferentially found in the lysosomal content (the lysosomal content arylamidase). Also a third arylamidase-active antigen was identified and was shown to be restricted to the microsomes and the lysosomal membranes (the microsomal/lysosomal arylamidase). The rat liver plasma membrane arylamidase-active antigen was also present in plasma membrane, microsomal and cell-sap fractions of both the hepatomas. However, in the hepatomas this antigen occurred predominantly in the microsomal fraction. The plasma membrane arylamidase was the only arylamidase-active antigen found in the hepatoma D33 while the plasma membrane and microsomal fractions of hepatoma D23 also contained another antigen with this activity. Neither the lysosomal content arylamidase nor the microsomal/lysosomal arylamidase could be detected in any of the hepatoma fractions.", "contents": "Arylamidases of rat liver and chemically induced hepatomas. 1. Subcellular distribution of L-leucine. 2. Naphthylamidase-active antigens. The subcellular distribution of arylamidase-active antigens in rat liver and in two chemically induced hepatomas (D23 and D33) was investigated. Soluble antigens or detergent-solubilized membrane antigens from isolated subcellular fractions were tested in fused rocket immunoelectrophoresis against antisera prepared against each of the fractions. The arylamidase active antigens were identified by means of a zymogram technique using L-leucine 2-naphthylamide as substrate. Two arylamidase-active antigens were shown to be shared between plasma membranes, microsomes, lysosomal membranes and lysosomal content of the hepatocytes. One of these occurred predominantly in the plasma membranes (the plasma membrane arylamidase) while the other was preferentially found in the lysosomal content (the lysosomal content arylamidase). Also a third arylamidase-active antigen was identified and was shown to be restricted to the microsomes and the lysosomal membranes (the microsomal/lysosomal arylamidase). The rat liver plasma membrane arylamidase-active antigen was also present in plasma membrane, microsomal and cell-sap fractions of both the hepatomas. However, in the hepatomas this antigen occurred predominantly in the microsomal fraction. The plasma membrane arylamidase was the only arylamidase-active antigen found in the hepatoma D33 while the plasma membrane and microsomal fractions of hepatoma D23 also contained another antigen with this activity. Neither the lysosomal content arylamidase nor the microsomal/lysosomal arylamidase could be detected in any of the hepatoma fractions."}
{"id": "PMID:192311", "title": "Calcium ion effects on cyclic adenosine 3':5'-monophosphate bindings to the plasma membrane of Dictyostelium discoideum.", "content": "The study of cell surface cyclic adenosine 3':5'-monophosphate binding to Dictyostelium discoideum amoebae indicates that Ca2+ increases the number of binding sites without significantly affecting their affinity constant(s). The effects of the ion are observed immediately (within 4 s after addition) and appear to be readily reversible. Ca2+ effects are observed at various temperatures and pH values and are not blocked by the presence of various metabolic inhibitors. Increases, and decreases, in the apparent number of cyclic nucleotide binding sites could also be effected by concanavalin A treatments which respectively stimulate, and inhibit cell differentiation.", "contents": "Calcium ion effects on cyclic adenosine 3':5'-monophosphate bindings to the plasma membrane of Dictyostelium discoideum. The study of cell surface cyclic adenosine 3':5'-monophosphate binding to Dictyostelium discoideum amoebae indicates that Ca2+ increases the number of binding sites without significantly affecting their affinity constant(s). The effects of the ion are observed immediately (within 4 s after addition) and appear to be readily reversible. Ca2+ effects are observed at various temperatures and pH values and are not blocked by the presence of various metabolic inhibitors. Increases, and decreases, in the apparent number of cyclic nucleotide binding sites could also be effected by concanavalin A treatments which respectively stimulate, and inhibit cell differentiation."}
{"id": "PMID:192312", "title": "Localization of the metabolic processes affected by calcium during corticotropin action.", "content": "To define the role of calcium during corticotropin-induced steroidogenesis, adrenal sections were incubated under conditions of varying degrees of calcium depletion. Corticosterone production, [14C]leucine incorporation into protein, and tissue cyclic AMP levels were measured concomitantly. Omitting calcium from the incubation media inhibited all three processes to variable extents, thus limiting conclusions regarding which process is most dependent on calcium. While calcium was required during the early phase of corticotropin action, it was not required during later phases: rapid induction of calcium deficiency did not diminish the heightened rate of steroidogenesis previously induced by corticotropin in the presence of calcium. Thus, while calcium is required for induction of steroidogenesis factor(s), the operation of the latter is not dependent upon calcium in the extracellular fluid.", "contents": "Localization of the metabolic processes affected by calcium during corticotropin action. To define the role of calcium during corticotropin-induced steroidogenesis, adrenal sections were incubated under conditions of varying degrees of calcium depletion. Corticosterone production, [14C]leucine incorporation into protein, and tissue cyclic AMP levels were measured concomitantly. Omitting calcium from the incubation media inhibited all three processes to variable extents, thus limiting conclusions regarding which process is most dependent on calcium. While calcium was required during the early phase of corticotropin action, it was not required during later phases: rapid induction of calcium deficiency did not diminish the heightened rate of steroidogenesis previously induced by corticotropin in the presence of calcium. Thus, while calcium is required for induction of steroidogenesis factor(s), the operation of the latter is not dependent upon calcium in the extracellular fluid."}
{"id": "PMID:192313", "title": "Hyperglucagonemia and altered responsiveness of hepatic adenylate cyclase-adenosine 3',5'-monophosphate system to hormonal stimulation during chronic ingestion of DL-ethionine.", "content": "Basal activity and hormonal responsiveness of the adenylate cyclase-adenosine 3',5'-monophosphate system were examined in premalignant liver from rats chronically fed the hepatic carcinogen DL-ethionine, and these data were correlated with endogenous levels of plasma glucagon. By 2 weeks basal hepatic cyclic AMP levels, determined in tissues quick-frozen in situ, were 2-fold higher in rats ingesting ethionine than in the pair-fed control. Enhanced tissue cyclic AM content was associated with an increase in the adenylate cyclase activity of whole homogenates of fresh liver from rats fed ethionine (68 +/- 5 pmol cyclic AMP/10 min per mg protein) compared to control (48 +/- 4). Cyclic AMP-dependent protein kinase activity ratios were also significantly higher (control, 0.38 +/- 0.04; ethionine 0.55 +/- 0.05) and the percent glycogen synthetase activity in the glucose 6-phosphate-independent form was markedly reduced (control, 52 +/- 7%; ethionine, 15 +/- 1.5%) in the livers of ethionine-fed rats compared to the controls, suggesting that the high total hepatic cyclic AMP which accompanied ethionine ingestion was bilogically effective. These changes persisted throughout the 38 weeks of drug ingestion. Immunoreactive glucagon levels, determined in portal venous plasma, were 8-fold higher than control after 2 weeks of the ethionine diet (control, 185 +/- 24 pg/ml; ethionine, 1532 +/- 195). Analogous to the changes in hepatic parameters, plasma glucagon levels remained elevated during the entire period of drug ingestion until the development of hepatomas. The hepatic cyclic AMP response to a maximal stimulatory dose of injected glucagon was blunted in vivo in ethionine-fed rats (control, 14 -fold increase over basal, to 8.63 +/- 1.1 pmol/mg wet weight; ethionine, 4.6-fold rise over basal, to 5.42 +/- 0.9). Reduced cyclic AMP responses to both maximal and submaximal glucagon stimulation were also evident in vitro in hepatic slices prepared from rats fed the drug, and the reduction was specific to glucagon. Absolute or relative hepatic cyclic AMP responses to maximally effective concentrations of protaglandin E1 or isoproterenol in hepatic slices from ethionine-fed rats were greater than or equal to those observed in control slices. Parallel alterations in hormonal responsiveness were observed in adenylate cyclase activity of whole homogenates of these livers, implying that the changes in cyclic AMP accumulation following hormone stimulation were related to an alteration in cyclic AMP generation in the premalignant tissue. In view of the recognized hepatic actions of glucagon and the desensitization of adenylate cyclase which can occur during sustained stimulation of the liver with this hormone, the endogenous hyperglucagonemia that accompanies ethionine ingestion could play a role in the pathogenesis of both the basal alterations in hepatic cyclic AMP metabolism and the reduced responsiveness to glucagon observed in liver from rats fed this carcinogen.", "contents": "Hyperglucagonemia and altered responsiveness of hepatic adenylate cyclase-adenosine 3',5'-monophosphate system to hormonal stimulation during chronic ingestion of DL-ethionine. Basal activity and hormonal responsiveness of the adenylate cyclase-adenosine 3',5'-monophosphate system were examined in premalignant liver from rats chronically fed the hepatic carcinogen DL-ethionine, and these data were correlated with endogenous levels of plasma glucagon. By 2 weeks basal hepatic cyclic AMP levels, determined in tissues quick-frozen in situ, were 2-fold higher in rats ingesting ethionine than in the pair-fed control. Enhanced tissue cyclic AM content was associated with an increase in the adenylate cyclase activity of whole homogenates of fresh liver from rats fed ethionine (68 +/- 5 pmol cyclic AMP/10 min per mg protein) compared to control (48 +/- 4). Cyclic AMP-dependent protein kinase activity ratios were also significantly higher (control, 0.38 +/- 0.04; ethionine 0.55 +/- 0.05) and the percent glycogen synthetase activity in the glucose 6-phosphate-independent form was markedly reduced (control, 52 +/- 7%; ethionine, 15 +/- 1.5%) in the livers of ethionine-fed rats compared to the controls, suggesting that the high total hepatic cyclic AMP which accompanied ethionine ingestion was bilogically effective. These changes persisted throughout the 38 weeks of drug ingestion. Immunoreactive glucagon levels, determined in portal venous plasma, were 8-fold higher than control after 2 weeks of the ethionine diet (control, 185 +/- 24 pg/ml; ethionine, 1532 +/- 195). Analogous to the changes in hepatic parameters, plasma glucagon levels remained elevated during the entire period of drug ingestion until the development of hepatomas. The hepatic cyclic AMP response to a maximal stimulatory dose of injected glucagon was blunted in vivo in ethionine-fed rats (control, 14 -fold increase over basal, to 8.63 +/- 1.1 pmol/mg wet weight; ethionine, 4.6-fold rise over basal, to 5.42 +/- 0.9). Reduced cyclic AMP responses to both maximal and submaximal glucagon stimulation were also evident in vitro in hepatic slices prepared from rats fed the drug, and the reduction was specific to glucagon. Absolute or relative hepatic cyclic AMP responses to maximally effective concentrations of protaglandin E1 or isoproterenol in hepatic slices from ethionine-fed rats were greater than or equal to those observed in control slices. Parallel alterations in hormonal responsiveness were observed in adenylate cyclase activity of whole homogenates of these livers, implying that the changes in cyclic AMP accumulation following hormone stimulation were related to an alteration in cyclic AMP generation in the premalignant tissue. In view of the recognized hepatic actions of glucagon and the desensitization of adenylate cyclase which can occur during sustained stimulation of the liver with this hormone, the endogenous hyperglucagonemia that accompanies ethionine ingestion could play a role in the pathogenesis of both the basal alterations in hepatic cyclic AMP metabolism and the reduced responsiveness to glucagon observed in liver from rats fed this carcinogen."}
{"id": "PMID:192314", "title": "Solubilization and characterization of hormone- responsive phosphodiesterase activity of rat fat cells.", "content": "Fat cells particulate phosphodiesterase activity can be solubilized in high yield (80--100%) in a buffer system (30 mM Tris - HCl, pH 8.0) containing non-ionic detergents (0.1% Brij 30, 1.0% Triton X-100), salt (3.0 mM MgSO4, 5.0 mM NaBr) and dithiothreitol (5.0 mM). Polyacrylamide gel electrophoresis of the solubilized enzyme activity indicated the presence of two bands of activities of different electrophoretic mobilities, both of which  hydrolyzed cyclic AMP and cyclic GMP. The solubilized activity eluted from DEAE Bio-Gel columns as a somewhat broad profile with at least two peaks of activity. Activity against both cyclic AMP and cyclic GMP eluted in similar but not identical patterns. The solubilized enzyme and DEAE column eluates wxhibited low (less than 1 micronM) Michaelis constants for cyclic AMP and cyclic GMP. In addition, the increases in phosphodiesterase activity induced by incubation of intact fat cells with insulin or adrenocorticotropic hormone are maintained in the solubilized state.", "contents": "Solubilization and characterization of hormone- responsive phosphodiesterase activity of rat fat cells. Fat cells particulate phosphodiesterase activity can be solubilized in high yield (80--100%) in a buffer system (30 mM Tris - HCl, pH 8.0) containing non-ionic detergents (0.1% Brij 30, 1.0% Triton X-100), salt (3.0 mM MgSO4, 5.0 mM NaBr) and dithiothreitol (5.0 mM). Polyacrylamide gel electrophoresis of the solubilized enzyme activity indicated the presence of two bands of activities of different electrophoretic mobilities, both of which  hydrolyzed cyclic AMP and cyclic GMP. The solubilized activity eluted from DEAE Bio-Gel columns as a somewhat broad profile with at least two peaks of activity. Activity against both cyclic AMP and cyclic GMP eluted in similar but not identical patterns. The solubilized enzyme and DEAE column eluates wxhibited low (less than 1 micronM) Michaelis constants for cyclic AMP and cyclic GMP. In addition, the increases in phosphodiesterase activity induced by incubation of intact fat cells with insulin or adrenocorticotropic hormone are maintained in the solubilized state."}
{"id": "PMID:192315", "title": "Stimulation of the activity of prolyl hydroxylase in 3T3 fibroblasts by 1,10-phenanthroline.", "content": "In confluent cultures of 3T3 fibroblasts, incubated for 24 h with 1,10-phenanthroline at 10(-5)--10(-9) M, the activity of prolyl hydroxylase was significantly increased. 1,10-Phenanthroline was inhibitory at concentrations greater than 10(-4) M. The stimulatory effect of 1,10-phenanthroline manifests itself after 6 h incubation and increased with time up to 48 h. 2,2'-dipyridyl and 5,6-dimethyl-1,10-phenanthroline were also stimulatory; a nonchelating analog, 1,7-phenanthroline had no effect. Cycloheximide did not modify the 1,10-phenanthroline effect. The stimulatory effect does not seem to depend on the shift of an inactive precursor of prolyl hydroxylase to an active form because 1,10-phenanthroline was shown to be ineffective in logarithmically growing cells. While dialysis of washed and homogenized cells significantly increased prolyl hydroxylase activity in cell extracts, undialyzed 1,10-phenanthroline treated samples exhibited higher prolyl hydroxylase activity than dialyzed controls. These data suggested to us that 1,10-phenanthroline and other chelating agents may be forming complexes with certain metal ions or protein-metal ions which are inhibitory towards prolyl hydroxylase.", "contents": "Stimulation of the activity of prolyl hydroxylase in 3T3 fibroblasts by 1,10-phenanthroline. In confluent cultures of 3T3 fibroblasts, incubated for 24 h with 1,10-phenanthroline at 10(-5)--10(-9) M, the activity of prolyl hydroxylase was significantly increased. 1,10-Phenanthroline was inhibitory at concentrations greater than 10(-4) M. The stimulatory effect of 1,10-phenanthroline manifests itself after 6 h incubation and increased with time up to 48 h. 2,2'-dipyridyl and 5,6-dimethyl-1,10-phenanthroline were also stimulatory; a nonchelating analog, 1,7-phenanthroline had no effect. Cycloheximide did not modify the 1,10-phenanthroline effect. The stimulatory effect does not seem to depend on the shift of an inactive precursor of prolyl hydroxylase to an active form because 1,10-phenanthroline was shown to be ineffective in logarithmically growing cells. While dialysis of washed and homogenized cells significantly increased prolyl hydroxylase activity in cell extracts, undialyzed 1,10-phenanthroline treated samples exhibited higher prolyl hydroxylase activity than dialyzed controls. These data suggested to us that 1,10-phenanthroline and other chelating agents may be forming complexes with certain metal ions or protein-metal ions which are inhibitory towards prolyl hydroxylase."}
{"id": "PMID:192316", "title": "Regulation of cyclic AMP level and lactic acid production in Ehrlich ascites tumor cells.", "content": "1. Quercetin (3.3',4',5,7-pentahydroxy flavone) at the concentration of 10(-4) M, as well as 2-10(-2) M theophylline and 1.5 - 10(-4) M prostaglandin E2 caused maximal rise of cyclic AMP in Ehrlich ascites tumor cells. 2. No additional increase of cyclic AMP level in these cells was found when both quercetin (10(-4) M) and theophylline (2-10(-2) M) were present in the incubation medium, while combination of quercetin (10(-4) M) and prostaglandin E2 (1.5 - 10(-4) M) has a synergistic effect on the level of cyclic AMP. 3. Degradation of cyclic AMP by homogenate of Ehrlich ascites tumor cells was inhibited by both quercetin and theophylline. 4. Quercetin, and to a smaller but significant extent theophylline, inhibited the lactic acid production in Ehrlich ascites tumor cells while prostaglandin E2 did not change the glycolytic rate in these cells. No synergistic inhibitory effect on lactic acid production was found when combinations of quercetin and prostaglandin E2, quercetin and theophylline or prostaglandin E2 and theophylline were tested. 5. Treatment of Ehrlich ascites tumor cells with dextran sulfate abolished the inhibitory effect of quercetin on lactic acid production, while the effect of the bioflavonoid on cyclic AMP levels was not altered.", "contents": "Regulation of cyclic AMP level and lactic acid production in Ehrlich ascites tumor cells. 1. Quercetin (3.3',4',5,7-pentahydroxy flavone) at the concentration of 10(-4) M, as well as 2-10(-2) M theophylline and 1.5 - 10(-4) M prostaglandin E2 caused maximal rise of cyclic AMP in Ehrlich ascites tumor cells. 2. No additional increase of cyclic AMP level in these cells was found when both quercetin (10(-4) M) and theophylline (2-10(-2) M) were present in the incubation medium, while combination of quercetin (10(-4) M) and prostaglandin E2 (1.5 - 10(-4) M) has a synergistic effect on the level of cyclic AMP. 3. Degradation of cyclic AMP by homogenate of Ehrlich ascites tumor cells was inhibited by both quercetin and theophylline. 4. Quercetin, and to a smaller but significant extent theophylline, inhibited the lactic acid production in Ehrlich ascites tumor cells while prostaglandin E2 did not change the glycolytic rate in these cells. No synergistic inhibitory effect on lactic acid production was found when combinations of quercetin and prostaglandin E2, quercetin and theophylline or prostaglandin E2 and theophylline were tested. 5. Treatment of Ehrlich ascites tumor cells with dextran sulfate abolished the inhibitory effect of quercetin on lactic acid production, while the effect of the bioflavonoid on cyclic AMP levels was not altered."}
{"id": "PMID:192317", "title": "Oxidation of C1-compounds in Pseudomonas C.", "content": "Extracts of Pseudomonas C grown on methanol as a sole carbon and energy source contain a methanol dehydrogenase activity which can be coupled to phenazine methosulfate. This enzyme catalyzes two reactions namely the conversion of methanol to formaldehyde (phenazine methosulfate coupled) and the oxidation of formaldehyde to formate (2,6-dichloroindophenol-coupled). Activities of glutathione-dependent formaldehyde dehydrogenase (NAD+) and formate dehydrogenase (NAD+) were also detected in the extracts. The addition of D-ribulose 5-phosphate to the reaction mixtures caused a marked increase in the formaldehyde-dependent reduction of NAD+ or NADP+. In addition, the oxidation of [14C]formaldehyde to CO2, by extracts of Pseudomonas C, increased when D-ribulose 5-phosphate was present in the assay mixtures. The amount of radioactivity found in CO2, was 6;8-times higher when extracts of methanol-grown Pseudomonas C were incubated for a short period of time with [1-14C]glucose 6-phosphate than with [U-14C]glucose 6-phosphate. These data, and the presence of high specific activities of hexulose phosphate synthase, phosphoglucoisomerase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase indicate that in methanol-grown Pseudomonas C, formaldehyde carbon is oxidized to CO2 both via a cyclic pathway which includes the enzymes mentioned and via formate as an oxidation intermediate, with the former predominant.", "contents": "Oxidation of C1-compounds in Pseudomonas C. Extracts of Pseudomonas C grown on methanol as a sole carbon and energy source contain a methanol dehydrogenase activity which can be coupled to phenazine methosulfate. This enzyme catalyzes two reactions namely the conversion of methanol to formaldehyde (phenazine methosulfate coupled) and the oxidation of formaldehyde to formate (2,6-dichloroindophenol-coupled). Activities of glutathione-dependent formaldehyde dehydrogenase (NAD+) and formate dehydrogenase (NAD+) were also detected in the extracts. The addition of D-ribulose 5-phosphate to the reaction mixtures caused a marked increase in the formaldehyde-dependent reduction of NAD+ or NADP+. In addition, the oxidation of [14C]formaldehyde to CO2, by extracts of Pseudomonas C, increased when D-ribulose 5-phosphate was present in the assay mixtures. The amount of radioactivity found in CO2, was 6;8-times higher when extracts of methanol-grown Pseudomonas C were incubated for a short period of time with [1-14C]glucose 6-phosphate than with [U-14C]glucose 6-phosphate. These data, and the presence of high specific activities of hexulose phosphate synthase, phosphoglucoisomerase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase indicate that in methanol-grown Pseudomonas C, formaldehyde carbon is oxidized to CO2 both via a cyclic pathway which includes the enzymes mentioned and via formate as an oxidation intermediate, with the former predominant."}
{"id": "PMID:192318", "title": "An electron paramagnetic resonance study of free radicals in cells.", "content": "An electron paramagnetic resonance study was performed on cell lines of the following strains: HeLa, 37RC, L, FLC, NRK/RSV, 3T3/SV40. Unsynchronized and synchronized HeLa cells were studied with particular attention paid to the relation between growth and free radical concentration. Free radical levels were shown to be a function of the growth stage and different phases of the cell cycle.", "contents": "An electron paramagnetic resonance study of free radicals in cells. An electron paramagnetic resonance study was performed on cell lines of the following strains: HeLa, 37RC, L, FLC, NRK/RSV, 3T3/SV40. Unsynchronized and synchronized HeLa cells were studied with particular attention paid to the relation between growth and free radical concentration. Free radical levels were shown to be a function of the growth stage and different phases of the cell cycle."}
{"id": "PMID:192319", "title": "Production of superoxide anions and hydrogen peroxide in Ehrlich ascites tumour cell nuclei.", "content": "Nuclei isolated from Ehrlich-Lettr\u00e9 ascites tumour cells catalyze the co-oxidation of epinephrine to adrenochrome in the presence of NADPH. Adrenochrome formation is sensitive to superoxide dismutase but not to scavengers of hydroxyl radicals or singlet oxygen. Addition of NADPH also initiates the production of hydrogen peroxide. Moreover measurements of superoxide dismutase activity indicate the presence of this enzyme in the ascites cell nuclei, although the sensitivity of adrenochrome formation to externally added superoxide dismutase indicates that the endogenous enzyme is not sufficient for a complete protection from superoxide radicals.", "contents": "Production of superoxide anions and hydrogen peroxide in Ehrlich ascites tumour cell nuclei. Nuclei isolated from Ehrlich-Lettr\u00e9 ascites tumour cells catalyze the co-oxidation of epinephrine to adrenochrome in the presence of NADPH. Adrenochrome formation is sensitive to superoxide dismutase but not to scavengers of hydroxyl radicals or singlet oxygen. Addition of NADPH also initiates the production of hydrogen peroxide. Moreover measurements of superoxide dismutase activity indicate the presence of this enzyme in the ascites cell nuclei, although the sensitivity of adrenochrome formation to externally added superoxide dismutase indicates that the endogenous enzyme is not sufficient for a complete protection from superoxide radicals."}
{"id": "PMID:192320", "title": "Reductive dechlorination of DDT by haem proteins.", "content": "DDT1 is converted to DDD by reduced myoglobin (rapidly), cytochrome c oxidase, and a haem-containing undecapeptide derived from cytochrome c. Cytochrome c itself is inactive. This demonstrates that an accessible haem site is necessary for the reaction. Spectrophotometric evidence is presented for an interaction between DDT and the undecapeptide. These results cast light on one of the biological pathways for the breakdown of DDT.", "contents": "Reductive dechlorination of DDT by haem proteins. DDT1 is converted to DDD by reduced myoglobin (rapidly), cytochrome c oxidase, and a haem-containing undecapeptide derived from cytochrome c. Cytochrome c itself is inactive. This demonstrates that an accessible haem site is necessary for the reaction. Spectrophotometric evidence is presented for an interaction between DDT and the undecapeptide. These results cast light on one of the biological pathways for the breakdown of DDT."}
{"id": "PMID:192324", "title": "Thermosensitive respiratory deficiency in yeast associated with specific effects on particulate cytochrome oxidase.", "content": "A mutant of Saccharomyces cerevisiae, unable to grow at the expense of non fermentable carbon sources at 37 degrees C, has been selected; at 25 degrees C the mutant strain behaves like the parental wild strain. Evaluations of respiration rates during aerobic growth at restrictive temperature on one hand, enzymatic and/or spectral evaluations of the individual components of the respiratory chain on the other hand show that the respiratory deficiency is specifically correlated with a reduced level of cytochrome oxidase. The decrease of enzyme activity is the direct consequence of a lowering of hemoprotein (a,a3) concentration. Temperature-activity relationship of cytochrome oxidase elaborated at the permissive temperature by the mutant strain is modified as far as the particulate enzyme is concerned, but no difference is observed after partial solubilization of the enzyme by non ionic surfactant. Genetic analysis shows that the mutant phenotype results from a nuclear gene mutation.", "contents": "Thermosensitive respiratory deficiency in yeast associated with specific effects on particulate cytochrome oxidase. A mutant of Saccharomyces cerevisiae, unable to grow at the expense of non fermentable carbon sources at 37 degrees C, has been selected; at 25 degrees C the mutant strain behaves like the parental wild strain. Evaluations of respiration rates during aerobic growth at restrictive temperature on one hand, enzymatic and/or spectral evaluations of the individual components of the respiratory chain on the other hand show that the respiratory deficiency is specifically correlated with a reduced level of cytochrome oxidase. The decrease of enzyme activity is the direct consequence of a lowering of hemoprotein (a,a3) concentration. Temperature-activity relationship of cytochrome oxidase elaborated at the permissive temperature by the mutant strain is modified as far as the particulate enzyme is concerned, but no difference is observed after partial solubilization of the enzyme by non ionic surfactant. Genetic analysis shows that the mutant phenotype results from a nuclear gene mutation."}
{"id": "PMID:192325", "title": "Multiple molecular forms of phosphorylase phosphatase associated with particulate glycogen and extracted from the cytosol of dog liver.", "content": "The glycogen pellet of dog liver extracts contains a phosphorylase phosphatase which has characteristics different from those of the phosphatases extracted from the cytosol. The phosphatase associated with glycogen is characterized by a M, of 51,000, a half maximal inhibition at 0.3 mM ATP (Hill coefficient : 2) and a Ki for Mg2+ of 1 mM. Treatment with urea or mercaptoethanol of the phosphatase associated with glycogen does not influence the activity, the Mr or the half maximal inhibition by ATP, but a decrease of the Hill coefficient for ATP is observed. A similar treatment of the phosphatases extracted from the high speed supernatant results in a decrease of the Mr of the spontaneously active form from 215,000 to 43,000, without an effect on the Ki for ATP (7 micronM), but accompanied by an increase in activity. The ATP-Mg dependent form of the phosphatase from the high speed supernatant (Mr : 138,000 ; Ka for ATP in the presence of 0.1 mM Mg2+ : 0.3 micronM), is denatured by urea or mercaptoethanol. The phosphatase associated with particulate glycogen cannot be found in the supernatant, nor the phosphorylase phosphatases present in the supernatant in the glycogen pellet. When all the glycogen is mobilized (starvation, glucagon) the phosphatase specifically associated with glycogen cannot be found as such in the cytosol. No activation of synthase beta can be detected neither with the phosphatases extracted from the cytosol nor with the enzyme released from the glycogen pellet.", "contents": "Multiple molecular forms of phosphorylase phosphatase associated with particulate glycogen and extracted from the cytosol of dog liver. The glycogen pellet of dog liver extracts contains a phosphorylase phosphatase which has characteristics different from those of the phosphatases extracted from the cytosol. The phosphatase associated with glycogen is characterized by a M, of 51,000, a half maximal inhibition at 0.3 mM ATP (Hill coefficient : 2) and a Ki for Mg2+ of 1 mM. Treatment with urea or mercaptoethanol of the phosphatase associated with glycogen does not influence the activity, the Mr or the half maximal inhibition by ATP, but a decrease of the Hill coefficient for ATP is observed. A similar treatment of the phosphatases extracted from the high speed supernatant results in a decrease of the Mr of the spontaneously active form from 215,000 to 43,000, without an effect on the Ki for ATP (7 micronM), but accompanied by an increase in activity. The ATP-Mg dependent form of the phosphatase from the high speed supernatant (Mr : 138,000 ; Ka for ATP in the presence of 0.1 mM Mg2+ : 0.3 micronM), is denatured by urea or mercaptoethanol. The phosphatase associated with particulate glycogen cannot be found in the supernatant, nor the phosphorylase phosphatases present in the supernatant in the glycogen pellet. When all the glycogen is mobilized (starvation, glucagon) the phosphatase specifically associated with glycogen cannot be found as such in the cytosol. No activation of synthase beta can be detected neither with the phosphatases extracted from the cytosol nor with the enzyme released from the glycogen pellet."}
{"id": "PMID:192326", "title": "The use of a complementary DNA probe to detect accumulation of mengo RNA in infected cells pretreated with interferon.", "content": "Complementary DNA (cDNA) from Mengo virus RNA has been synthesized and used as a probe to measure the synthesis and accumulation of viral RNA in Mengo infected L cell cultures, treated or untreated with interferon. Under experimental conditions used (200 units interferon/ml and 50 virus plaque-forming units/cell) results show that there is some synthesis of Mengo virus RNA in cells treated with interferon. One hour after infection, treated cells contain three times less viral RNA than untreated cells; five hours after infection, this difference has increased to ten fold. As in the control, no fragmented Mengo virus RNA molecules were found in interferon treated cells. The smaller recovery of infectious particles from interferon treated cells as compared to RNA accumulation suggests that not only RNA accumulation is inhibited but also a step posterior in viral maturation.", "contents": "The use of a complementary DNA probe to detect accumulation of mengo RNA in infected cells pretreated with interferon. Complementary DNA (cDNA) from Mengo virus RNA has been synthesized and used as a probe to measure the synthesis and accumulation of viral RNA in Mengo infected L cell cultures, treated or untreated with interferon. Under experimental conditions used (200 units interferon/ml and 50 virus plaque-forming units/cell) results show that there is some synthesis of Mengo virus RNA in cells treated with interferon. One hour after infection, treated cells contain three times less viral RNA than untreated cells; five hours after infection, this difference has increased to ten fold. As in the control, no fragmented Mengo virus RNA molecules were found in interferon treated cells. The smaller recovery of infectious particles from interferon treated cells as compared to RNA accumulation suggests that not only RNA accumulation is inhibited but also a step posterior in viral maturation."}
{"id": "PMID:192329", "title": "[Some characteristics of isoenzymic spectrum of hexokinase and glucose levels in hepatomas and liver of the host].", "content": "The total activity of hexokinase (HK) and HK isoenzymic spectrum of the normal liver and slowly groming hepatoma 49 did not show any essential differences. However, the HK total activity and the relative and absolute contents of isoenzyme HK-3 were increased in hepatomas 61 and especially in the rapidly growing hepatoma 22-a. The glucokinase activity decreases in the hepatiomas 49 and 61 and disappears in the rapidly growing hepatoma 22-a. The glucose content in hepatoma 49 was slightly lower than in the normal liver, whereas in other hepatoma no traces of glucose could be detected. At low glucose concentration in the medium (0,1 mM), i.e. under conditions simulating those characteristic of tumors in vivo, the predominant form of HK in all hepatomas studied was found to be HK-3. In the liver of hepatoma-bearing mice some shifts in the value of total HK activity and its isoenzymic spectrum, reminding one of those found in hepatomas themselves, were observed. Unequal deviations in the total HK activity and its isoenzymic spectrum in hepatomas with different degrees of malignancy indicate that these characteristics are secondary rather than primary events depending on tumour progression.", "contents": "[Some characteristics of isoenzymic spectrum of hexokinase and glucose levels in hepatomas and liver of the host]. The total activity of hexokinase (HK) and HK isoenzymic spectrum of the normal liver and slowly groming hepatoma 49 did not show any essential differences. However, the HK total activity and the relative and absolute contents of isoenzyme HK-3 were increased in hepatomas 61 and especially in the rapidly growing hepatoma 22-a. The glucokinase activity decreases in the hepatiomas 49 and 61 and disappears in the rapidly growing hepatoma 22-a. The glucose content in hepatoma 49 was slightly lower than in the normal liver, whereas in other hepatoma no traces of glucose could be detected. At low glucose concentration in the medium (0,1 mM), i.e. under conditions simulating those characteristic of tumors in vivo, the predominant form of HK in all hepatomas studied was found to be HK-3. In the liver of hepatoma-bearing mice some shifts in the value of total HK activity and its isoenzymic spectrum, reminding one of those found in hepatomas themselves, were observed. Unequal deviations in the total HK activity and its isoenzymic spectrum in hepatomas with different degrees of malignancy indicate that these characteristics are secondary rather than primary events depending on tumour progression."}
{"id": "PMID:192330", "title": "[Phosphorylation of some thiamine analogs by yeast thiamine pyrophosphokinase].", "content": "A rapid efficient method of separation of the thiamine pyrophosphokinase reaction products (ATP: thiamine pyrophosphotransferase) on the column packed with DEAE-Sephadex A-25 and their subsequent identification by direct spectrophotometry is suggested. Phosphorylation of some thiamine analogs substituted at the second position of the pyrimidine ring was studied. It was shown that in addition to thiamine, the enzyme transfers the pyrophosphate group to some of its derivatives. The vitamin analogs devoid of quaternary nitrogen in the thiazole cycle, do not form pyrophosphate ethers (thus being unable to act as substrates), whereas 2'-phenoxythiamine, 2'-methoxythiamine and especially 2'-phenylthiamine are phosphorylated at a greater rate than does the \"true\" substrate, thiamine, under similar conditions.", "contents": "[Phosphorylation of some thiamine analogs by yeast thiamine pyrophosphokinase]. A rapid efficient method of separation of the thiamine pyrophosphokinase reaction products (ATP: thiamine pyrophosphotransferase) on the column packed with DEAE-Sephadex A-25 and their subsequent identification by direct spectrophotometry is suggested. Phosphorylation of some thiamine analogs substituted at the second position of the pyrimidine ring was studied. It was shown that in addition to thiamine, the enzyme transfers the pyrophosphate group to some of its derivatives. The vitamin analogs devoid of quaternary nitrogen in the thiazole cycle, do not form pyrophosphate ethers (thus being unable to act as substrates), whereas 2'-phenoxythiamine, 2'-methoxythiamine and especially 2'-phenylthiamine are phosphorylated at a greater rate than does the \"true\" substrate, thiamine, under similar conditions."}
{"id": "PMID:192331", "title": "[Mitochondrial menadione reductase: kinetics and mechanism of the action in situ].", "content": "The formal mechanism of action of menadion reductase localized in the membrane of intact mitochondria in the rebox reaction of 4-N (p-sulfoanilin)-5-methoxy-1,2-benzoquinone with NADH as an electron donor has been studied by the stationary kinetics method. It has been shown that the mitochondrial menadion reductase incorporated into the membrane functions according to the \"ping-pong\" mechanism, similar to the functioning of the free enzyme. However, in this case an inhibitory effect of NADH has been noticed. A phenomenological equation, which is in a good accordance with the experimental data, has been suggested. Luminescence studies showed that a specific NADH-binding site located outside the active centre exists in the enzyme molecule. The model of the mechanism of the enzyme substrate inhibition in situ, responsible for a change in the conformation of the apoenzyme occurs upon NADH binding, is discussed.", "contents": "[Mitochondrial menadione reductase: kinetics and mechanism of the action in situ]. The formal mechanism of action of menadion reductase localized in the membrane of intact mitochondria in the rebox reaction of 4-N (p-sulfoanilin)-5-methoxy-1,2-benzoquinone with NADH as an electron donor has been studied by the stationary kinetics method. It has been shown that the mitochondrial menadion reductase incorporated into the membrane functions according to the \"ping-pong\" mechanism, similar to the functioning of the free enzyme. However, in this case an inhibitory effect of NADH has been noticed. A phenomenological equation, which is in a good accordance with the experimental data, has been suggested. Luminescence studies showed that a specific NADH-binding site located outside the active centre exists in the enzyme molecule. The model of the mechanism of the enzyme substrate inhibition in situ, responsible for a change in the conformation of the apoenzyme occurs upon NADH binding, is discussed."}
{"id": "PMID:192332", "title": "[Comparative characteristics of cytosol glucocorticoid receptors from normal liver, the liver of tumor-bearing rats and hormone unresponsive Zajdela hepatoma].", "content": "Specific dexametasone (D) and cortisol (F) receptors have been found both in liver and Zajdela hepatoma. Rat liver cytosol receptors are characterized by the association constant (Kas) = 3,8 X 10(8) M-1 for D and 0,57 X 10(8) M-1 for F as well as by a number of binding sites (NBS)=4,9 X 10(-13) moles/mg protein and 4,06 X 10(-13) moles/mg protein, respectively. The receptors show stric specificity to glucocorticoids. Cytosol glucocorticoid-receptor complexes from liver and hepatoma sediment at 6-7S, when centrifuged in the buffer of a low ionic strength, and at 3-4S in the buffer of a high ionic strength (0,4 M KCl). The properties of cytosol receptors in the course of in vivo hepatoma growth were found to be gradually altering: Kas for D dropped whereas that for F increased; the NBS is decreased 3-4 fold as compared to normal liver cytosol--which may partially be accounted for by the unresponsiveness of the tumour to the hormones.", "contents": "[Comparative characteristics of cytosol glucocorticoid receptors from normal liver, the liver of tumor-bearing rats and hormone unresponsive Zajdela hepatoma]. Specific dexametasone (D) and cortisol (F) receptors have been found both in liver and Zajdela hepatoma. Rat liver cytosol receptors are characterized by the association constant (Kas) = 3,8 X 10(8) M-1 for D and 0,57 X 10(8) M-1 for F as well as by a number of binding sites (NBS)=4,9 X 10(-13) moles/mg protein and 4,06 X 10(-13) moles/mg protein, respectively. The receptors show stric specificity to glucocorticoids. Cytosol glucocorticoid-receptor complexes from liver and hepatoma sediment at 6-7S, when centrifuged in the buffer of a low ionic strength, and at 3-4S in the buffer of a high ionic strength (0,4 M KCl). The properties of cytosol receptors in the course of in vivo hepatoma growth were found to be gradually altering: Kas for D dropped whereas that for F increased; the NBS is decreased 3-4 fold as compared to normal liver cytosol--which may partially be accounted for by the unresponsiveness of the tumour to the hormones."}
{"id": "PMID:192333", "title": "[The formation of ATP from adenosine 5'-phosphoroimidazolide and pyrophosphate catalyzed by valyl-tRNA-synthetase].", "content": "The formation of 32P-ATP from adenosine 5'-phosphoroimidazolide and 32P-pyrophosphate brought about valine: tRNA-ligase of E. coli is demonstrated in the standard conditions of pyrophosphate exchange for aminoacyl-tRNA synthetases. The role the enzyme as specific matrix is suggested.", "contents": "[The formation of ATP from adenosine 5'-phosphoroimidazolide and pyrophosphate catalyzed by valyl-tRNA-synthetase]. The formation of 32P-ATP from adenosine 5'-phosphoroimidazolide and 32P-pyrophosphate brought about valine: tRNA-ligase of E. coli is demonstrated in the standard conditions of pyrophosphate exchange for aminoacyl-tRNA synthetases. The role the enzyme as specific matrix is suggested."}
{"id": "PMID:192334", "title": "[Comparative study of nuclear RNA of the liver and experimental hepatoma by the method of DNA-RNA molecular hybridization].", "content": "DNA:RNA molecular hybridization of rat liver and hepatoma nyclear RNAs was carried out under controlled conditions as to nucleotide composition and quantitative ratios of competing RNAs and the time of labelling. These factors are shown to influence the results of competition hybridization experiments. For instance a lower competitive ability of rat liver nuclear RNA as compared to that of hepatoma nuclear RNA stems to certain from a relatively higher GC-content of the former. However differences in the competitive efficiency of nuclear RNAs studied could be revealed even with preparations of equal nucleotide composition, these differences being but of quantitative character. The results of the experiments suggest that hepatoma nuclear RNAs are relatively rich in the fast-hybridizable fraction which does not differ qualitatively from the corresponding fraction is characterized by a high metabolic activity and certain tissue specifity.", "contents": "[Comparative study of nuclear RNA of the liver and experimental hepatoma by the method of DNA-RNA molecular hybridization]. DNA:RNA molecular hybridization of rat liver and hepatoma nyclear RNAs was carried out under controlled conditions as to nucleotide composition and quantitative ratios of competing RNAs and the time of labelling. These factors are shown to influence the results of competition hybridization experiments. For instance a lower competitive ability of rat liver nuclear RNA as compared to that of hepatoma nuclear RNA stems to certain from a relatively higher GC-content of the former. However differences in the competitive efficiency of nuclear RNAs studied could be revealed even with preparations of equal nucleotide composition, these differences being but of quantitative character. The results of the experiments suggest that hepatoma nuclear RNAs are relatively rich in the fast-hybridizable fraction which does not differ qualitatively from the corresponding fraction is characterized by a high metabolic activity and certain tissue specifity."}
{"id": "PMID:192335", "title": "[Halidor, 1-benzyl-1-(3'-dimethylaminopropoxy)-cyclohep tane fumarate as an uncoupler and inhibitor of the respiratory chain].", "content": "Halidor 1-benzyl-1-(3'-dimethylaminopropoxy)-cycloheptane fumarate, activates succinate oxidation in mitochondria and inhibits reverse electron transport from succinate to NAD+ in submitochondrial partides preparations at doses of 2-10(-5)--10(-3) M. At a dose of 5--7-10(-4) M halidor cause a swelling of mitochondria incubated in 0.1 M NH4NO3. At higher concentrations (10(-3)--10(-2) M) halidor practically completely inhibits NADH and succinate oxidase activity of mitochondria and submitochondrial particles. It is suggested that vasodilating effect of halidor is due to the uncoupling of oxidative phosphorylation, thus causing a deficiency of ATP for contracting function of blood vessel muscles.", "contents": "[Halidor, 1-benzyl-1-(3'-dimethylaminopropoxy)-cyclohep tane fumarate as an uncoupler and inhibitor of the respiratory chain]. Halidor 1-benzyl-1-(3'-dimethylaminopropoxy)-cycloheptane fumarate, activates succinate oxidation in mitochondria and inhibits reverse electron transport from succinate to NAD+ in submitochondrial partides preparations at doses of 2-10(-5)--10(-3) M. At a dose of 5--7-10(-4) M halidor cause a swelling of mitochondria incubated in 0.1 M NH4NO3. At higher concentrations (10(-3)--10(-2) M) halidor practically completely inhibits NADH and succinate oxidase activity of mitochondria and submitochondrial particles. It is suggested that vasodilating effect of halidor is due to the uncoupling of oxidative phosphorylation, thus causing a deficiency of ATP for contracting function of blood vessel muscles."}
{"id": "PMID:192336", "title": "[Mitochondrial thymidine kinase and ribonucleotide reductase from rat liver and rat hepatoma 27].", "content": "Fractions of heavy and light mitochondria are isolated from homogenates of homologous rat tissues (intact liver, regenerating liver within 24 hours after hepatectomy and 27 hepatoma) by means of differential centrifugation. It is found that tumour mitochondria have higher heterogeneity and lower buyoant density than mitochondria from normal hepatocytes. The activity of two enzymes of DNA precursors synthesis (ribonucleotide reductase and thymidine kinase) in subcellular fractions is demonstrated to correlate with the tissue growth rate. A single injection of cyclic AMP into hepatectomised rats resulted in the retardation of the regeneration process, and the activity of both enzymes reached its normal level in all the fractions studied after 24 hours after the operation. Thymidine kinase and ribonucleotide reductase are located mainly in the mitochondrial matrix, however, pronounced enzyme activity is observed also in membrane fractions. The activity of the enzymes in the fraction of external mitochondria membranes in rapidly growing tissues is 2--3 times as high as in the same fraction from normal rat liver.", "contents": "[Mitochondrial thymidine kinase and ribonucleotide reductase from rat liver and rat hepatoma 27]. Fractions of heavy and light mitochondria are isolated from homogenates of homologous rat tissues (intact liver, regenerating liver within 24 hours after hepatectomy and 27 hepatoma) by means of differential centrifugation. It is found that tumour mitochondria have higher heterogeneity and lower buyoant density than mitochondria from normal hepatocytes. The activity of two enzymes of DNA precursors synthesis (ribonucleotide reductase and thymidine kinase) in subcellular fractions is demonstrated to correlate with the tissue growth rate. A single injection of cyclic AMP into hepatectomised rats resulted in the retardation of the regeneration process, and the activity of both enzymes reached its normal level in all the fractions studied after 24 hours after the operation. Thymidine kinase and ribonucleotide reductase are located mainly in the mitochondrial matrix, however, pronounced enzyme activity is observed also in membrane fractions. The activity of the enzymes in the fraction of external mitochondria membranes in rapidly growing tissues is 2--3 times as high as in the same fraction from normal rat liver."}
{"id": "PMID:192337", "title": "[Biosynthesis of cardiolipin in the rat hepatoma 27 and Jensen sarcoma].", "content": "The localization of cardiolipin biosynthesis in rat hepatoma 27 and Jensen sarcoma cells was investigated. In both tumors cardiolipin was found to be synthesized only in the mitochondria as is the case in normal rat liver. It is concluded that the occurrence of cardiolipin in the microsomes of the tumor cells may be connected with a transmembrane exchange of phospholipids in vivo.", "contents": "[Biosynthesis of cardiolipin in the rat hepatoma 27 and Jensen sarcoma]. The localization of cardiolipin biosynthesis in rat hepatoma 27 and Jensen sarcoma cells was investigated. In both tumors cardiolipin was found to be synthesized only in the mitochondria as is the case in normal rat liver. It is concluded that the occurrence of cardiolipin in the microsomes of the tumor cells may be connected with a transmembrane exchange of phospholipids in vivo."}
{"id": "PMID:192338", "title": "[Potentiation of in vitro lipolytic effect of ACTH by its fragment].", "content": "The influence of fragment ACTH 11-14 analogues with amino acid sequences H-Lys-Pro-Val-Gly-OH (fragment I) and H-Lys-Pro-Val-Gly-NH2 (fragment II), possessing structural elements, similar for certain groups of peptide hormones and kinins, on lipolytic effect of ACTH in adipose tissue and isolated epydidymal fat cells of rat, was studied. Both fragments have no effect on the lipolysis; they potentiate the ACTH-induced lipolysis 1,5--2,0 fold, but do not alter the maximal effect at concentrations 0,1--1,0 mkg/ml in tissue and fragment I--at concentrations from 0,01 to 0,1 mkg/ml in isolated fat cell system. The role of \"common\" fragments in hormone-receptor interactions as well as mechanism of their potentiating effect is discussed. It is assumed that the \"common\" fragment of ACTH--ACTH11-14--is a second, non-specific active site of hormone directly involved in secondary signal formation.", "contents": "[Potentiation of in vitro lipolytic effect of ACTH by its fragment]. The influence of fragment ACTH 11-14 analogues with amino acid sequences H-Lys-Pro-Val-Gly-OH (fragment I) and H-Lys-Pro-Val-Gly-NH2 (fragment II), possessing structural elements, similar for certain groups of peptide hormones and kinins, on lipolytic effect of ACTH in adipose tissue and isolated epydidymal fat cells of rat, was studied. Both fragments have no effect on the lipolysis; they potentiate the ACTH-induced lipolysis 1,5--2,0 fold, but do not alter the maximal effect at concentrations 0,1--1,0 mkg/ml in tissue and fragment I--at concentrations from 0,01 to 0,1 mkg/ml in isolated fat cell system. The role of \"common\" fragments in hormone-receptor interactions as well as mechanism of their potentiating effect is discussed. It is assumed that the \"common\" fragment of ACTH--ACTH11-14--is a second, non-specific active site of hormone directly involved in secondary signal formation."}
{"id": "PMID:192339", "title": "[Estimation of kinetic constants and study of site specificity of Zajdela ascite hepatoma and rat liver tRNA-methylases].", "content": "Individual yeast tRNAVal1 was used as a substrate for estimation of kinetic constants and study of site specificity of m5C-and m1A-methylases of Zajdela ascite hepatoma and rat liver. It was demonstrated that the rate of yeast tRNAVal1 methylation by hepatoma tRNA-methylases is 4--5 times higher than that induced by liver tRNA-methylases. The rates of 1-hour methyl groups incorporation into tRNAVal1 were 3.7 and 4.7 times higher in case of m5C-and m1A-methylases and 9.4 and 4.5 times higher in case of m1G-and m7G-methylases of hepatoma than the respective rates obtained for corresponding liver methylases. The main products of methylation were m5C and m1A containing about 90% of total radioactivity incorporated into tRNA. m5C-methylases of liver and hepatoma had similar affinity for S-Ad-Met. The Km value for both enzymes was 2.66 micronmole; the Km values for m1A-methylases of liver and hepatoma with respect to S-Ad-Met were the same and equal to 0,25 micronmole. m5C and m1A methylases of liver and hepatoma had adequate affinity for yeast tRNAVal1; their site specificity was the same, since they methylated in yeast tRNAVal1 cytosine in the tetracytidylic sequence of C49--C52 and adenine in the 59th position from the 5'-end of the molecule.", "contents": "[Estimation of kinetic constants and study of site specificity of Zajdela ascite hepatoma and rat liver tRNA-methylases]. Individual yeast tRNAVal1 was used as a substrate for estimation of kinetic constants and study of site specificity of m5C-and m1A-methylases of Zajdela ascite hepatoma and rat liver. It was demonstrated that the rate of yeast tRNAVal1 methylation by hepatoma tRNA-methylases is 4--5 times higher than that induced by liver tRNA-methylases. The rates of 1-hour methyl groups incorporation into tRNAVal1 were 3.7 and 4.7 times higher in case of m5C-and m1A-methylases and 9.4 and 4.5 times higher in case of m1G-and m7G-methylases of hepatoma than the respective rates obtained for corresponding liver methylases. The main products of methylation were m5C and m1A containing about 90% of total radioactivity incorporated into tRNA. m5C-methylases of liver and hepatoma had similar affinity for S-Ad-Met. The Km value for both enzymes was 2.66 micronmole; the Km values for m1A-methylases of liver and hepatoma with respect to S-Ad-Met were the same and equal to 0,25 micronmole. m5C and m1A methylases of liver and hepatoma had adequate affinity for yeast tRNAVal1; their site specificity was the same, since they methylated in yeast tRNAVal1 cytosine in the tetracytidylic sequence of C49--C52 and adenine in the 59th position from the 5'-end of the molecule."}
{"id": "PMID:192340", "title": "[On hexokinase isozymes].", "content": "Electrophoretic study of hexokinase (HK) associated with the soluble fraction of mouse transplantable hepatoma 22a revealed that almost all bands of HK activities overlapped the bands of glucose-6-P dehydrogenase (G6PDH) activities in the gels. Similar results were obtained for liver, muscle and brain soluble fractions, as well as for various extracts from hepatoma 22a mitochondria and commercial preparation of yeast HK. A single type of HK, which does not overlap G6PDH activity, was located between types I and II (according to the Katzen classification) as a diffuse band of 1 hour manifestation. A possibility of structural organization of glycolytic enzymes in the cell essential for the quantitative estimation of the isozyme pattern is discussed.", "contents": "[On hexokinase isozymes]. Electrophoretic study of hexokinase (HK) associated with the soluble fraction of mouse transplantable hepatoma 22a revealed that almost all bands of HK activities overlapped the bands of glucose-6-P dehydrogenase (G6PDH) activities in the gels. Similar results were obtained for liver, muscle and brain soluble fractions, as well as for various extracts from hepatoma 22a mitochondria and commercial preparation of yeast HK. A single type of HK, which does not overlap G6PDH activity, was located between types I and II (according to the Katzen classification) as a diffuse band of 1 hour manifestation. A possibility of structural organization of glycolytic enzymes in the cell essential for the quantitative estimation of the isozyme pattern is discussed."}
{"id": "PMID:192341", "title": "[Cytochrome c immobilized on Sepharose 4B and its participation in photochemical reactions of chloroplasts].", "content": "Cytochrome c immobilized on cyanogen bromide-activated Sepharose 4B may be used to study photochemical reactions in chloroplasts. Chloroplast reduction of both immobilized and soluble forms of the cytochrome occurs along the exogenous and endogenous pathways which results in a weaker reduction of the immobilized protein as compared to that of the soluble one. The time of the reduced immobilized cytochrome c oxidation in the dark is two orders of magnitude greater than that of the soluble one. This fact may be interpreted in terms of spatial dissociation of reductase and oxidase centers of chloroplasts with reference to the cytochrome. The optimal ionic strength for cytochrome reduction, i.e. ionic strength causing an in vitro destruction of the ferredoxin-NADP-reductase complex was found to equal to 0.2 M.", "contents": "[Cytochrome c immobilized on Sepharose 4B and its participation in photochemical reactions of chloroplasts]. Cytochrome c immobilized on cyanogen bromide-activated Sepharose 4B may be used to study photochemical reactions in chloroplasts. Chloroplast reduction of both immobilized and soluble forms of the cytochrome occurs along the exogenous and endogenous pathways which results in a weaker reduction of the immobilized protein as compared to that of the soluble one. The time of the reduced immobilized cytochrome c oxidation in the dark is two orders of magnitude greater than that of the soluble one. This fact may be interpreted in terms of spatial dissociation of reductase and oxidase centers of chloroplasts with reference to the cytochrome. The optimal ionic strength for cytochrome reduction, i.e. ionic strength causing an in vitro destruction of the ferredoxin-NADP-reductase complex was found to equal to 0.2 M."}
{"id": "PMID:192342", "title": "[Tumor growth and protein synthesis in mouse hepatoma 22A cells under antitumor effect of N-methyl-N-nitrosourea].", "content": "A single injection of N-methyl-N-nitrosourea results in simultaneous long-term inhibition of tumor growth and protein synthesis in mouse hepatoma 22a cells. These effects are tightly connected: onset of tumor regrowth starts only after a full recovery of the activity of the protein synthetic machinery of tumor cells.", "contents": "[Tumor growth and protein synthesis in mouse hepatoma 22A cells under antitumor effect of N-methyl-N-nitrosourea]. A single injection of N-methyl-N-nitrosourea results in simultaneous long-term inhibition of tumor growth and protein synthesis in mouse hepatoma 22a cells. These effects are tightly connected: onset of tumor regrowth starts only after a full recovery of the activity of the protein synthetic machinery of tumor cells."}
{"id": "PMID:192344", "title": "[Interaction of thiamine pyrophosphokinase from brewer's yeast with thiamine and adenosine-5'-triphosphate].", "content": "The interaction of thiamine pyrophosphokinase (Thiaminkinase EC 2.7.6.2) with thiamine and ATP was studied. It was shown that the mechanism of the thiaminokinase reactions is Rapid Equilibrium Random Bi -- Bi. The enzyme binds 8 moles ATP and 1 mole thiamine per mole protein Ks = 0,8-10(-3) and 4.10(-6) M for ATP and thiamine respectively.", "contents": "[Interaction of thiamine pyrophosphokinase from brewer's yeast with thiamine and adenosine-5'-triphosphate]. The interaction of thiamine pyrophosphokinase (Thiaminkinase EC 2.7.6.2) with thiamine and ATP was studied. It was shown that the mechanism of the thiaminokinase reactions is Rapid Equilibrium Random Bi -- Bi. The enzyme binds 8 moles ATP and 1 mole thiamine per mole protein Ks = 0,8-10(-3) and 4.10(-6) M for ATP and thiamine respectively."}
{"id": "PMID:192345", "title": "[The use of certain new O-benzoquinone derivatives as acceptor substrates in enzymatic oxidation of NADH].", "content": "A possibility of the use of new aliphatic and aminoarylic o-benzoquinone derivatives as acceptor substrates in NADH oxidation catalyzed by NAD(P)H: (acceptor)-oxidoreductase (EC 1.6.99.2) was demonstrated. The kinetic mechanism of this reaction was studied in a monosubstrate approach and the effective kinetic constants were determined. The stability of these o-benzoquinone derivatives in the oxidation-reduction reactions, including anzymic reduction and subsequent auto-oxidation of their diphenolic forms by oxygen, was substantiated using spectrophotometric techniques.", "contents": "[The use of certain new O-benzoquinone derivatives as acceptor substrates in enzymatic oxidation of NADH]. A possibility of the use of new aliphatic and aminoarylic o-benzoquinone derivatives as acceptor substrates in NADH oxidation catalyzed by NAD(P)H: (acceptor)-oxidoreductase (EC 1.6.99.2) was demonstrated. The kinetic mechanism of this reaction was studied in a monosubstrate approach and the effective kinetic constants were determined. The stability of these o-benzoquinone derivatives in the oxidation-reduction reactions, including anzymic reduction and subsequent auto-oxidation of their diphenolic forms by oxygen, was substantiated using spectrophotometric techniques."}
{"id": "PMID:192346", "title": "[Use of a fluorescent probe for the study of the active center of D-glyceraldehyde-3-phosphate dehydrogenase].", "content": "The effect of NAD on the binding of 1-anilino-8-naphthalene sulfonate (ANS) to yeast glyceraldehyde-3-phosphate dehydrogenase has been studied using difference spectrophotometric and fluorescence techniques. Coenzyme addition causes the displacement of ANS from its complex with  the dehydrogenase, as suggested by the effect of NAD on the fluorescence of the enzyme--ANS complex, as well as on the magnitude of the difference spectrum of the complex. Adenine containing NAD fragments, adenosine, 5'-AMP, and ADP were shown to compete with ANS for the common site on the enzyme using fluorimetric technique; in the case of adenosine and 5'-AMP a direct method of analytical ultracentrifugation was also employed. The results obtained by both methods suggest the dye binding at the adenine subsite of the dehydrogenase. The interaction with ANS causes no detectable conformational changes of the protein. The fluorescence of the dye-enzyme complex increases and the emission maximum shifts to shorter wavelengths on addition of nicotinamide mononucleotide. This suggest some conformational changes to occur in the microenvironment of the bound dye in response to the interaction with the ligand in the nicotinamide subsite. The participation of the nicotinamide subsite of the active center in determining the character of conformational transitions associated with coenzyme binding to glyceraldehyde-3-phosphate dehydrogenase is discussed.", "contents": "[Use of a fluorescent probe for the study of the active center of D-glyceraldehyde-3-phosphate dehydrogenase]. The effect of NAD on the binding of 1-anilino-8-naphthalene sulfonate (ANS) to yeast glyceraldehyde-3-phosphate dehydrogenase has been studied using difference spectrophotometric and fluorescence techniques. Coenzyme addition causes the displacement of ANS from its complex with  the dehydrogenase, as suggested by the effect of NAD on the fluorescence of the enzyme--ANS complex, as well as on the magnitude of the difference spectrum of the complex. Adenine containing NAD fragments, adenosine, 5'-AMP, and ADP were shown to compete with ANS for the common site on the enzyme using fluorimetric technique; in the case of adenosine and 5'-AMP a direct method of analytical ultracentrifugation was also employed. The results obtained by both methods suggest the dye binding at the adenine subsite of the dehydrogenase. The interaction with ANS causes no detectable conformational changes of the protein. The fluorescence of the dye-enzyme complex increases and the emission maximum shifts to shorter wavelengths on addition of nicotinamide mononucleotide. This suggest some conformational changes to occur in the microenvironment of the bound dye in response to the interaction with the ligand in the nicotinamide subsite. The participation of the nicotinamide subsite of the active center in determining the character of conformational transitions associated with coenzyme binding to glyceraldehyde-3-phosphate dehydrogenase is discussed."}
{"id": "PMID:192347", "title": "[Interrelationship between NAD metabolism and DNA synthesis in chicken liver nuclei during ontogenesis].", "content": "The content of NAD and DNA, the activity of DNA-polymerase the velocity of NAD pyrophosphorolysis have been studied in liver nuclei of 8, 14, 18 day-old chicken embryos and 1--2 month- and 6 month-old chickens. It has been found that during ontogenesis the NAD content in chicken liver nuclei is increased, whereas the DNA content is decreased, the correlation coefficient being--0,93. The DNA-polymerase activity is the highest in the liver nuclei of 8--14 day-old embryos. During ontogenesis the DNA-polymerase activity is decreased. The excess of inorganic pyrophosphate shifts the NAD synthesis reaction to the left and activates the NAD pyrophosphorolytic degradation. During chicken ontogenesis the maximal NAD pyrophosphorolytic degradation is observed during the embrionic period.", "contents": "[Interrelationship between NAD metabolism and DNA synthesis in chicken liver nuclei during ontogenesis]. The content of NAD and DNA, the activity of DNA-polymerase the velocity of NAD pyrophosphorolysis have been studied in liver nuclei of 8, 14, 18 day-old chicken embryos and 1--2 month- and 6 month-old chickens. It has been found that during ontogenesis the NAD content in chicken liver nuclei is increased, whereas the DNA content is decreased, the correlation coefficient being--0,93. The DNA-polymerase activity is the highest in the liver nuclei of 8--14 day-old embryos. During ontogenesis the DNA-polymerase activity is decreased. The excess of inorganic pyrophosphate shifts the NAD synthesis reaction to the left and activates the NAD pyrophosphorolytic degradation. During chicken ontogenesis the maximal NAD pyrophosphorolytic degradation is observed during the embrionic period."}
{"id": "PMID:192348", "title": "[Structurally functional organization of corticotropin: lipolytic and steroidogenic activity of some of its fragments].", "content": "The influence of ACTH fragments, possessing structural elements, common for certain groups of peptide hormones and kinins--\"common\" fragments and cluster of basic amino-acids--(Lys 17,18-ACTH 11-18-NH2--I; ACTH 11-13-NH2--II; NH2CO-ACTH18-20-NH2--III) on lipolytic effect of ACTH in rat isolated fat cells and on the steroidogenic effect of ACTH in isolated rat adrenal cells was studied. Fragment I exerts a steroidogenic effect (alpha=0,84) at concentrations of 1--100 microng/ml. At low concentrations (10(-8)--10(-3) microng/ml) fragment I potentiates ACTH-induced steroidogenesis. Fragment I has no effect on the lipolysis;however, it potentiates ACTH-induced lipolysis at concentrations of 10--100 microng/ml. The results obtained support our previous supposition that \"common\" fragments are essential secondary non-specific active sites of hormones.", "contents": "[Structurally functional organization of corticotropin: lipolytic and steroidogenic activity of some of its fragments]. The influence of ACTH fragments, possessing structural elements, common for certain groups of peptide hormones and kinins--\"common\" fragments and cluster of basic amino-acids--(Lys 17,18-ACTH 11-18-NH2--I; ACTH 11-13-NH2--II; NH2CO-ACTH18-20-NH2--III) on lipolytic effect of ACTH in rat isolated fat cells and on the steroidogenic effect of ACTH in isolated rat adrenal cells was studied. Fragment I exerts a steroidogenic effect (alpha=0,84) at concentrations of 1--100 microng/ml. At low concentrations (10(-8)--10(-3) microng/ml) fragment I potentiates ACTH-induced steroidogenesis. Fragment I has no effect on the lipolysis;however, it potentiates ACTH-induced lipolysis at concentrations of 10--100 microng/ml. The results obtained support our previous supposition that \"common\" fragments are essential secondary non-specific active sites of hormones."}
{"id": "PMID:192349", "title": "[Functional interrelations between isozymes of dehydrogenases in the intact and denervated rabbit muscles].", "content": "A correlation is shown to exist between malate dehydrogenase (MDH), lactate dehydrogenase (LDH) and glycerol-3-phosphate dehydrogenase (glycerol-3-PDH activity values, lactate/pyruvate and malate/oxaloacetate coefficients, MDH and LDH isozyme spectra and kinetic properties of LDH isozymes in soluble fractions of cytoplasm from intact rabbit m. soleus (red), m. gastrocnemius (mixed) and m. quadratus lumborum (white). In denervated soleus and gastrocnemius the cytoplasmic MDH/LDH, mitochondrial MDH/LDH, MDH mitochondrial/MDH cytoplasmic activity ratios, concentrations of substrates and isozyme spectra of MDH and LDH tend to equalize. The obtained results indicate the importance of isozyme composition and total activity ratios of the dehydrogenases for regulation of pyruvate and NADH metabolic pathways.", "contents": "[Functional interrelations between isozymes of dehydrogenases in the intact and denervated rabbit muscles]. A correlation is shown to exist between malate dehydrogenase (MDH), lactate dehydrogenase (LDH) and glycerol-3-phosphate dehydrogenase (glycerol-3-PDH activity values, lactate/pyruvate and malate/oxaloacetate coefficients, MDH and LDH isozyme spectra and kinetic properties of LDH isozymes in soluble fractions of cytoplasm from intact rabbit m. soleus (red), m. gastrocnemius (mixed) and m. quadratus lumborum (white). In denervated soleus and gastrocnemius the cytoplasmic MDH/LDH, mitochondrial MDH/LDH, MDH mitochondrial/MDH cytoplasmic activity ratios, concentrations of substrates and isozyme spectra of MDH and LDH tend to equalize. The obtained results indicate the importance of isozyme composition and total activity ratios of the dehydrogenases for regulation of pyruvate and NADH metabolic pathways."}
{"id": "PMID:192350", "title": "[Fatty acid composition and unsaturated of intracellular membrane phospholipids from rat liver and hepatoma 27].", "content": "The fatty acid composition of phospholipids of mitochondria and microsomes from rat liver and hepatoma 27 was investigated. Basing on the fatty acid and phospholipid composition the unsaturation of the lipid bilayer of the intracellular membranes was calculated. The unsaturation of the phospholipids of the hepatoma mitochondria and microsomes was found to be much lower than that of the corresponding rat liver membranes. The lipid bilayer of the rat liver and hepatoma plasma membranes was shown to be more saturated than that of the intracellular membranes.", "contents": "[Fatty acid composition and unsaturated of intracellular membrane phospholipids from rat liver and hepatoma 27]. The fatty acid composition of phospholipids of mitochondria and microsomes from rat liver and hepatoma 27 was investigated. Basing on the fatty acid and phospholipid composition the unsaturation of the lipid bilayer of the intracellular membranes was calculated. The unsaturation of the phospholipids of the hepatoma mitochondria and microsomes was found to be much lower than that of the corresponding rat liver membranes. The lipid bilayer of the rat liver and hepatoma plasma membranes was shown to be more saturated than that of the intracellular membranes."}
{"id": "PMID:192351", "title": "[Comparison of structural and functional organization of adrenocorticotropic hormone and wasp kinin].", "content": "A comparative study of structural and functional organization of the polypeptides -- ACTH and wasp kinin was made. The effects of fragments Lys 17, 18-ACTH11(-18)-NH2--(I) and WK4(-12)--(II), possessing \"common\" fragments and a cluster of basic amino-acids, on the lipolytic and steroidogenic effects of ACTH and myotropic effects of bradykinin were studied. Both fragments I and II potentiate ACTH-induced lipolysis and steroidogenesis in isolated rat fat and adrenal cells but suppress the myotropic effect of bradykinin on guinea pig ileum. The similarity of biological effects of ACTH and WK fragments support our supposition on the similarity in structurally functional organization of these peptides.", "contents": "[Comparison of structural and functional organization of adrenocorticotropic hormone and wasp kinin]. A comparative study of structural and functional organization of the polypeptides -- ACTH and wasp kinin was made. The effects of fragments Lys 17, 18-ACTH11(-18)-NH2--(I) and WK4(-12)--(II), possessing \"common\" fragments and a cluster of basic amino-acids, on the lipolytic and steroidogenic effects of ACTH and myotropic effects of bradykinin were studied. Both fragments I and II potentiate ACTH-induced lipolysis and steroidogenesis in isolated rat fat and adrenal cells but suppress the myotropic effect of bradykinin on guinea pig ileum. The similarity of biological effects of ACTH and WK fragments support our supposition on the similarity in structurally functional organization of these peptides."}
{"id": "PMID:192352", "title": "Plasma indolethylamine-n-methyltransferase activity and growth hormone level during sleep: a pilot study.", "content": "Polygraphic recordings and sequential growth hormone (GH) samplings were performed in eight healthy adult males. In the plasma samples from seven of the subjects, indolethylamine-N-methyltransferase (INMT) activity was also determined. Five of eight subjects showed significant fluctuation in plasma GH level, and six of seven subjects showed significant fluctuation in plasma INMT activity level. There were also significant positive correlations between plasma GH and INMT activity level during the second episode of NREM sleep stage 1 and during the third episode of NREM sleep stage 2. A significant negative correlation between plasma GH and INMT activity level during the seventh episode of sleep stage 2 and during the fifth episode of post sleep-onset wake was found. In view of a previous finding that INMT activity in the serum of psychiatric patients is positively correlated with severity of delusions, the observation that NREM sleep is associated with mental activity characterized by repetitive thoughts, and the result that GH level in plasma is increased in NREM sleep early at night, our present findings suggest the hypotheses that increased plasma INMT activity during sleep is indicative of both increased INMT activity in the central nervous system (CNS) and the activation or maintenance of NREM mental activity during sleep. Additional research will be needed in order to validate our observations and test these hypotheses.", "contents": "Plasma indolethylamine-n-methyltransferase activity and growth hormone level during sleep: a pilot study. Polygraphic recordings and sequential growth hormone (GH) samplings were performed in eight healthy adult males. In the plasma samples from seven of the subjects, indolethylamine-N-methyltransferase (INMT) activity was also determined. Five of eight subjects showed significant fluctuation in plasma GH level, and six of seven subjects showed significant fluctuation in plasma INMT activity level. There were also significant positive correlations between plasma GH and INMT activity level during the second episode of NREM sleep stage 1 and during the third episode of NREM sleep stage 2. A significant negative correlation between plasma GH and INMT activity level during the seventh episode of sleep stage 2 and during the fifth episode of post sleep-onset wake was found. In view of a previous finding that INMT activity in the serum of psychiatric patients is positively correlated with severity of delusions, the observation that NREM sleep is associated with mental activity characterized by repetitive thoughts, and the result that GH level in plasma is increased in NREM sleep early at night, our present findings suggest the hypotheses that increased plasma INMT activity during sleep is indicative of both increased INMT activity in the central nervous system (CNS) and the activation or maintenance of NREM mental activity during sleep. Additional research will be needed in order to validate our observations and test these hypotheses."}
{"id": "PMID:192353", "title": "The effects of gamma-hydroxybutyrate on sleep.", "content": "Sodium gamma-hydroxybutyrate (GHB) is a remarkably safe and nontoxic hypnotic agent which is reported to be free of addicting properties. It is also a normal metabolite of the mammalian nervous system. We examined its effects on the sleep-EEG of eight patients with histories of impaired sleep, as a prelude to a more detailed study of its clinical potential. Sleep induced with GHB was indistinguishable subjectively from natural sleep as well as by behavioral and electroencephalographic criteria. Unlike most synthetic hypnotics, GHB increased delta sleep and did not suppress REM sleep. It shortened the REM sleep latency and shifted REM sleep into the first third of the night. On one occasion it induced a sleep onset REM period which was experienced as an attack of sleep paralysis. Withdrawal was simple; there was no REM sleep rebound and sleep patterns immediately returned to their pre-drug form. Its major clinical drawback was its short duration of action: its hypnotic effect lasting only 2 to 3 hr. We suggest that GHB may serve as the prototype for a new class of hypnotic compounds derived from natural sources and capable of activating the neurological mechanisms of normal human sleep.", "contents": "The effects of gamma-hydroxybutyrate on sleep. Sodium gamma-hydroxybutyrate (GHB) is a remarkably safe and nontoxic hypnotic agent which is reported to be free of addicting properties. It is also a normal metabolite of the mammalian nervous system. We examined its effects on the sleep-EEG of eight patients with histories of impaired sleep, as a prelude to a more detailed study of its clinical potential. Sleep induced with GHB was indistinguishable subjectively from natural sleep as well as by behavioral and electroencephalographic criteria. Unlike most synthetic hypnotics, GHB increased delta sleep and did not suppress REM sleep. It shortened the REM sleep latency and shifted REM sleep into the first third of the night. On one occasion it induced a sleep onset REM period which was experienced as an attack of sleep paralysis. Withdrawal was simple; there was no REM sleep rebound and sleep patterns immediately returned to their pre-drug form. Its major clinical drawback was its short duration of action: its hypnotic effect lasting only 2 to 3 hr. We suggest that GHB may serve as the prototype for a new class of hypnotic compounds derived from natural sources and capable of activating the neurological mechanisms of normal human sleep."}
{"id": "PMID:192356", "title": "Erythrocyte membrane phosphorylation in hereditary spherocytosis.", "content": "Phosphorylation of erythrocyte membrane proteins by membrane protein kinases was studied in 10 normal subjects and 8 patients with hereditary spherocytosis. No difference between the two groups of subjects was observed in the total phosphorylation, and, the phosphorylation of spectrin and components III and IV 5 in presence and in absence of 3',5'-cyclic AMP. So, no deficiency of membrane protein kinase activity seems to be present in hereditary spherocytosis.", "contents": "Erythrocyte membrane phosphorylation in hereditary spherocytosis. Phosphorylation of erythrocyte membrane proteins by membrane protein kinases was studied in 10 normal subjects and 8 patients with hereditary spherocytosis. No difference between the two groups of subjects was observed in the total phosphorylation, and, the phosphorylation of spectrin and components III and IV 5 in presence and in absence of 3',5'-cyclic AMP. So, no deficiency of membrane protein kinase activity seems to be present in hereditary spherocytosis."}
{"id": "PMID:192377", "title": "[Characteristics of cerebral electrical activity in rabbits with experimental herpetic encephalitis].", "content": "Examinations carried out on 33 rabbits with an experimental herpetic encpehalitis showed changes in the electrical activity of the brain correlating with the clinical picture of the disease. A diffus slowing down of the biopotentials and paroxysmal activity of two types--the paroxysmal periodic complexes and the complexes 'spike +the paroxysmal 3/sec' was revealed during the acute period of encephalitis.", "contents": "[Characteristics of cerebral electrical activity in rabbits with experimental herpetic encephalitis]. Examinations carried out on 33 rabbits with an experimental herpetic encpehalitis showed changes in the electrical activity of the brain correlating with the clinical picture of the disease. A diffus slowing down of the biopotentials and paroxysmal activity of two types--the paroxysmal periodic complexes and the complexes 'spike +the paroxysmal 3/sec' was revealed during the acute period of encephalitis."}
{"id": "PMID:192378", "title": "[Role of specific iodothyronine-binding proteins in the process of nuclear-cytoplasmic thyroid hormone interrelationships in liver cells].", "content": "A study was made of the role played by specific iodinethyrodine-binding proteins of rat hepatocytes in the process of nucleo-cytoplasmic interrelations of the thyroid hormones under normal conditions in thyroidectomy and in experimental thyrotoxicosis. The concentration of the hormone-binding sites in the cell depended on the thyroid hormone level outside the cell. An important role of the cytosol hormone-binding proteins in the accumulation and interacellular distribution of the thyroid cell hormones is emphasized. The absence of any participation of cytosol triiodine-thyronine binding proteins in the process ofpenetration of the hormone into the nucleus was revealed. Triiodine-thyronine level in the nuclei depended directly on the concentration of the recptor proteins in them and the degree of occupation of the acceptor sites in the receptors proper.", "contents": "[Role of specific iodothyronine-binding proteins in the process of nuclear-cytoplasmic thyroid hormone interrelationships in liver cells]. A study was made of the role played by specific iodinethyrodine-binding proteins of rat hepatocytes in the process of nucleo-cytoplasmic interrelations of the thyroid hormones under normal conditions in thyroidectomy and in experimental thyrotoxicosis. The concentration of the hormone-binding sites in the cell depended on the thyroid hormone level outside the cell. An important role of the cytosol hormone-binding proteins in the accumulation and interacellular distribution of the thyroid cell hormones is emphasized. The absence of any participation of cytosol triiodine-thyronine binding proteins in the process ofpenetration of the hormone into the nucleus was revealed. Triiodine-thyronine level in the nuclei depended directly on the concentration of the recptor proteins in them and the degree of occupation of the acceptor sites in the receptors proper."}
{"id": "PMID:192380", "title": "[Mechanism of action of ouabain and cyclic-3',5'-adenosine monophosphate on calcium ion transport in rat cardiac mitochondria].", "content": "Ouabain and cyclic AMP action on the Ca2+-accumulating capacity and the efflux of Ca2+ions from the loaded mitochondria of the rat heart was investigated by the tetracycline probe method. On the basis of the experimental results a conclusion was drawn that ouabain failed to act on these processes. Cyclic AMP didn't act on the Ca binding by the mitochondrial membrane; at the same time it induced rapid release of calcium from the loaded mitochondria.", "contents": "[Mechanism of action of ouabain and cyclic-3',5'-adenosine monophosphate on calcium ion transport in rat cardiac mitochondria]. Ouabain and cyclic AMP action on the Ca2+-accumulating capacity and the efflux of Ca2+ions from the loaded mitochondria of the rat heart was investigated by the tetracycline probe method. On the basis of the experimental results a conclusion was drawn that ouabain failed to act on these processes. Cyclic AMP didn't act on the Ca binding by the mitochondrial membrane; at the same time it induced rapid release of calcium from the loaded mitochondria."}
{"id": "PMID:192381", "title": "[Fluorimetric determination of the concentration of histamine and serotonin in the mast cells of ordinary and germ-free rats following administration of reserpine and cyclic adenosine-3',5'-monophosphate].", "content": "The microspectrometric method was applied to the determination of the content of histamine (a test with orthophthalic aldehyde) and serotonin (Falk's test) in the mast cells of the mesentery of common and germfree rats. Reserpine (10 mg/kg of body weight, intramuscularly) failed to alter histamine content, whereas serotonin content fell by 50%. Administration of cyclic AMP (3.5 mg/kg of body weight, intraperitoneally) led to the increase in serotonin content by 80%, and histamine--by 280--320%.", "contents": "[Fluorimetric determination of the concentration of histamine and serotonin in the mast cells of ordinary and germ-free rats following administration of reserpine and cyclic adenosine-3',5'-monophosphate]. The microspectrometric method was applied to the determination of the content of histamine (a test with orthophthalic aldehyde) and serotonin (Falk's test) in the mast cells of the mesentery of common and germfree rats. Reserpine (10 mg/kg of body weight, intramuscularly) failed to alter histamine content, whereas serotonin content fell by 50%. Administration of cyclic AMP (3.5 mg/kg of body weight, intraperitoneally) led to the increase in serotonin content by 80%, and histamine--by 280--320%."}
{"id": "PMID:192382", "title": "[Effect of cyclic nucleotides and isopropylnoradrenaline on oxygen tension and absorption].", "content": "Isopropylnoradrenaline (ISO), 3',5'-AMP and dibutyryl-3',5'-AMP decreased the oxygen tension (pO2) in the liver and the spleen and increased the body oxygen consumption (VO2). Time dynamics of these two effects was closely correlated for ISO and 3',5'-AMP. An increase of heat output was not accompanied by any significant changes in the respiration coefficient. Pempidine and dihydroergotamine failed to prevent 3',5'-AMP effects; inderal somewhat decreased these effects. Apparently, the catecholamine influence upon pO2 was a result of the VO2 increase through 3'5'-AMP effects are largely direct, but they include the in vivo and beta-receptor component; 2',3'-AMP decreased pO2 and VO2.", "contents": "[Effect of cyclic nucleotides and isopropylnoradrenaline on oxygen tension and absorption]. Isopropylnoradrenaline (ISO), 3',5'-AMP and dibutyryl-3',5'-AMP decreased the oxygen tension (pO2) in the liver and the spleen and increased the body oxygen consumption (VO2). Time dynamics of these two effects was closely correlated for ISO and 3',5'-AMP. An increase of heat output was not accompanied by any significant changes in the respiration coefficient. Pempidine and dihydroergotamine failed to prevent 3',5'-AMP effects; inderal somewhat decreased these effects. Apparently, the catecholamine influence upon pO2 was a result of the VO2 increase through 3'5'-AMP effects are largely direct, but they include the in vivo and beta-receptor component; 2',3'-AMP decreased pO2 and VO2."}
{"id": "PMID:192383", "title": "[Effect of etimizol on energy metabolism in rat brain].", "content": "Intraperitoneal injection of ethimizol in a dose of 25 mg/kg caused in intensification of the oxidative phosphorylion, an increase in creatine phosphate and a reduction of inorganic phosphorus concentration in the tissue of the rat brain. It is supposed that stimulation of the energy metabolism by ethimizol was caused by its activating effect on adenyylcyclase.", "contents": "[Effect of etimizol on energy metabolism in rat brain]. Intraperitoneal injection of ethimizol in a dose of 25 mg/kg caused in intensification of the oxidative phosphorylion, an increase in creatine phosphate and a reduction of inorganic phosphorus concentration in the tissue of the rat brain. It is supposed that stimulation of the energy metabolism by ethimizol was caused by its activating effect on adenyylcyclase."}
{"id": "PMID:192384", "title": "[Rate of progress of the 1st post-stimulation division of the mitotic cycle by cells of ascitic hepatoma 22A of different ages].", "content": "A study was made of the progress rate of cells of the ascitic hepatoma 22A of different age during the iirst mitotic cycle after the stimulation of division. The \"ageing\" (11-day), terminal (14-day), and \"delayed\" (4 days older than the terminal stage) ascitic fluids were used. The maximal values of the labeled nuclei index was found to be reached by 9--12 hours (it was mainly due to the transtion of the quiescent to the S-period) and the maximal mitotic index--by 18--21 hours after the inoculation, independently of the tumour age. These results suggest that the duration of both the prereplicative (G1) period and of the whole first mitotic cycle after the stimulation were independent of the time during which the cells of the ascitic hepatoma 22A were at the resting stage or at the very prolonged G1-period.", "contents": "[Rate of progress of the 1st post-stimulation division of the mitotic cycle by cells of ascitic hepatoma 22A of different ages]. A study was made of the progress rate of cells of the ascitic hepatoma 22A of different age during the iirst mitotic cycle after the stimulation of division. The \"ageing\" (11-day), terminal (14-day), and \"delayed\" (4 days older than the terminal stage) ascitic fluids were used. The maximal values of the labeled nuclei index was found to be reached by 9--12 hours (it was mainly due to the transtion of the quiescent to the S-period) and the maximal mitotic index--by 18--21 hours after the inoculation, independently of the tumour age. These results suggest that the duration of both the prereplicative (G1) period and of the whole first mitotic cycle after the stimulation were independent of the time during which the cells of the ascitic hepatoma 22A were at the resting stage or at the very prolonged G1-period."}
{"id": "PMID:192385", "title": "[Role of adrenergic structures of the central nervous system in altering the function of the hypothalamo-hypophyseo-adrenal system in exogenous hyperthermia].", "content": "Subcutaneous injection of chlorpromazine to rats caused a lesser increase in body temperature and a higher content of the corticotropin-releasing factor (CRF) in the hypothalamus and the ACTH in the hypophysis under conditions of exogenous hyperthermia. The ascorbic acid content in the adrenal glands decreased in the same way as in the animals overheated without any chlorpromazine. There was no significant change in the weight of the adrenal gland. A conclusion was drawn on the participation of the central adrenergic structure in the regulation of the synthesis or the secretion of the CRF.", "contents": "[Role of adrenergic structures of the central nervous system in altering the function of the hypothalamo-hypophyseo-adrenal system in exogenous hyperthermia]. Subcutaneous injection of chlorpromazine to rats caused a lesser increase in body temperature and a higher content of the corticotropin-releasing factor (CRF) in the hypothalamus and the ACTH in the hypophysis under conditions of exogenous hyperthermia. The ascorbic acid content in the adrenal glands decreased in the same way as in the animals overheated without any chlorpromazine. There was no significant change in the weight of the adrenal gland. A conclusion was drawn on the participation of the central adrenergic structure in the regulation of the synthesis or the secretion of the CRF."}
{"id": "PMID:192386", "title": "[Change in the resistance of partially hepatectomized mice to transplanted tumors in the period of liver regeneration completion].", "content": "There were two inhibition periods of the growth of ascitic hepatoma 22a when its cells were transplanted intraperitoneally to partially hepatectomized A/he mice 1 to 12 days after the operation. The first inhibition took place when the transplantation was performed one day, and the second--3 to 10 days, after partial hepatectomy. The animals which were most resistant to this tumour (5 to 8 days after the operation) proved to be resistant, although to a lesser extent, to the intraperitoneal transplantation of sarcoma 37 and Ehrlich's adenocarcinoma.", "contents": "[Change in the resistance of partially hepatectomized mice to transplanted tumors in the period of liver regeneration completion]. There were two inhibition periods of the growth of ascitic hepatoma 22a when its cells were transplanted intraperitoneally to partially hepatectomized A/he mice 1 to 12 days after the operation. The first inhibition took place when the transplantation was performed one day, and the second--3 to 10 days, after partial hepatectomy. The animals which were most resistant to this tumour (5 to 8 days after the operation) proved to be resistant, although to a lesser extent, to the intraperitoneal transplantation of sarcoma 37 and Ehrlich's adenocarcinoma."}
{"id": "PMID:192387", "title": "[Binding of 2-acetylaminofluorene-9-14C with rat liver nucleic acids during malignization and in primary hepatomas].", "content": "The residual binding of 9-14C-2-Acetylaminofluorene (9-14C-2-AAF) with rat liver nuclei acids was investigated during hepatocarcinogenesis two weeks after a single injection of 9-14C-2-AAF. Up to 6 months feeding of the animals with unlabeled 2-AAF, the RNA of their liver proved to bind increased amounts of 9-14C-2-AAF in comparison with normal liver. The binding of 9-14C-2-AAF with DNA in primary hepatomas was mainly due to the RNA heterodispersed components with the maximum level in the 18S-fraction, as well as with the biopolymere fractions with the sedimentation constant of 10 and 5S enriched with polyadenylate fragments.", "contents": "[Binding of 2-acetylaminofluorene-9-14C with rat liver nucleic acids during malignization and in primary hepatomas]. The residual binding of 9-14C-2-Acetylaminofluorene (9-14C-2-AAF) with rat liver nuclei acids was investigated during hepatocarcinogenesis two weeks after a single injection of 9-14C-2-AAF. Up to 6 months feeding of the animals with unlabeled 2-AAF, the RNA of their liver proved to bind increased amounts of 9-14C-2-AAF in comparison with normal liver. The binding of 9-14C-2-AAF with DNA in primary hepatomas was mainly due to the RNA heterodispersed components with the maximum level in the 18S-fraction, as well as with the biopolymere fractions with the sedimentation constant of 10 and 5S enriched with polyadenylate fragments."}
{"id": "PMID:192388", "title": "[Role of macrophage destruction products in the alveolar phagocytosis reaction].", "content": "Peritoneal macrophages (PM) of Wistar rats harvested after the intraperitoneal injection of paraffin oil were destroyed by repeated freezing-thawing. When injected intratracheally to control rats or to those after 4 daily exposured to TiO2 dust, these macrophage destruction products (MDP) caused a significant rise of both the alveolar macrophages (AM) and the neutrophilic leukocytes (NL) counts in the pulmonary washing-outs; the mean NL/AM ratio increased several times as compared to rats injected with normal saline intratracheally. Thus, the response to the inert dust particles plus the exogenous MDP became similar to the one observed after the cytotoxic (for instance silica) particles inhalation. Enhancing the NL contribution to the inhaled particles phagocytosis, the MDP led to a significant decrease of the mean \"Dust load\" of a single AM, although the total number of the engulfed particles increased. The predominant attraction of granulocytes and particularly of the NL as compared to the peritoneal macrophages was also found in the peritoneal exudates of rats injected with the MDP or silica suspension intraperitoneally, while the alveolar phagocytosis was not influenced. In vitro the MDP was shown to stimulate the NL migration and to facilitate the O2 consumption by PM. A possible role of the MDP as a multipotent controlling factor of phagocytosis response is briefly discussed.", "contents": "[Role of macrophage destruction products in the alveolar phagocytosis reaction]. Peritoneal macrophages (PM) of Wistar rats harvested after the intraperitoneal injection of paraffin oil were destroyed by repeated freezing-thawing. When injected intratracheally to control rats or to those after 4 daily exposured to TiO2 dust, these macrophage destruction products (MDP) caused a significant rise of both the alveolar macrophages (AM) and the neutrophilic leukocytes (NL) counts in the pulmonary washing-outs; the mean NL/AM ratio increased several times as compared to rats injected with normal saline intratracheally. Thus, the response to the inert dust particles plus the exogenous MDP became similar to the one observed after the cytotoxic (for instance silica) particles inhalation. Enhancing the NL contribution to the inhaled particles phagocytosis, the MDP led to a significant decrease of the mean \"Dust load\" of a single AM, although the total number of the engulfed particles increased. The predominant attraction of granulocytes and particularly of the NL as compared to the peritoneal macrophages was also found in the peritoneal exudates of rats injected with the MDP or silica suspension intraperitoneally, while the alveolar phagocytosis was not influenced. In vitro the MDP was shown to stimulate the NL migration and to facilitate the O2 consumption by PM. A possible role of the MDP as a multipotent controlling factor of phagocytosis response is briefly discussed."}
{"id": "PMID:192389", "title": "[Cell cultures obtained using collalytin from the pancreases of cattle fetuses].", "content": "The authors present morphological characteristics of primary monolayer cultures prepared from the pancreas of bovine fetuses. Combined treatment with trypsin and collalytine solutions (a preparation with collagenase activity) was used for dispersion of the tissue of the pancreas. Numerous epithelial cells corresponding by morphofunctional characteristics to beta-cells of the islets of Langerhans were contained in be cultures obtained; an aldehyde-fuchsin-positive granularity was revealed in the cytoplasm of these cells. Degranulation of these cells occurred under the effect of an increased glucose concentration in the nutrient medium.", "contents": "[Cell cultures obtained using collalytin from the pancreases of cattle fetuses]. The authors present morphological characteristics of primary monolayer cultures prepared from the pancreas of bovine fetuses. Combined treatment with trypsin and collalytine solutions (a preparation with collagenase activity) was used for dispersion of the tissue of the pancreas. Numerous epithelial cells corresponding by morphofunctional characteristics to beta-cells of the islets of Langerhans were contained in be cultures obtained; an aldehyde-fuchsin-positive granularity was revealed in the cytoplasm of these cells. Degranulation of these cells occurred under the effect of an increased glucose concentration in the nutrient medium."}
{"id": "PMID:192390", "title": "[Relationship between a state of sleep and wakefulness and transmission of an afferent signal through the posterior ventral nucleus of the thalamus].", "content": "Chronic experiments were carried out on nonanesthetized cats. A study was made of peculiarities attending the transmission of the afferent signals and the following inhibitory processes in the posterior ventral nucleus of the thalamus, depending on the state of sleep and wakefulness. Transmission of the signals decreases during the dreaming condition and the slow-wave sleep, and increases during the active states of alert cats. In paradoxical sleep the signal transmission is at the same level as such at resting wakeful condition. A marked transmission fluctuation is seen during the dreaming state and in the course of the first phase of sleep. The level of signal transmission is the most stable during the active states. The degree of the trance inhibitory process after the afferent signal transmission depends on the level of anesthesia, wakefulness and natural sleep. Processes following the afferent signal transmission in the posterior ventral nucleus of the thalamus show a radical difference in the barbituiate-anesthetized in comparison with nonanesthetized animals. The trace inhibition, so characteristic of anesthesia, was expressed in the dreaming state of the animal but insignificantly; in the wakeful condition it is not manifested at all.", "contents": "[Relationship between a state of sleep and wakefulness and transmission of an afferent signal through the posterior ventral nucleus of the thalamus]. Chronic experiments were carried out on nonanesthetized cats. A study was made of peculiarities attending the transmission of the afferent signals and the following inhibitory processes in the posterior ventral nucleus of the thalamus, depending on the state of sleep and wakefulness. Transmission of the signals decreases during the dreaming condition and the slow-wave sleep, and increases during the active states of alert cats. In paradoxical sleep the signal transmission is at the same level as such at resting wakeful condition. A marked transmission fluctuation is seen during the dreaming state and in the course of the first phase of sleep. The level of signal transmission is the most stable during the active states. The degree of the trance inhibitory process after the afferent signal transmission depends on the level of anesthesia, wakefulness and natural sleep. Processes following the afferent signal transmission in the posterior ventral nucleus of the thalamus show a radical difference in the barbituiate-anesthetized in comparison with nonanesthetized animals. The trace inhibition, so characteristic of anesthesia, was expressed in the dreaming state of the animal but insignificantly; in the wakeful condition it is not manifested at all."}
{"id": "PMID:192391", "title": "[Depressor reactions to sural nerve stimulation in intact unanesthetized cats].", "content": "Changes in the arterial pressure, in the heart and respiratory rate evoked by the gastrocnemuis nerve stimulation were studied on conscious cats before and during intravenous injection of noradrenaline. Stimulation of the gastrocnemius nerve increased the arterial pressure, the heart and respiratory rates. The same stimulation of the nerve during hypertension caused by noradrenaline injection led to the fall of arterial pressure and tachycardia. The depressor response failed to change under the effect of the beta-adrenoreceptor block and disappeared after the m-cholinoreceptor block with methylatropine. The depressor response was absent in the unanesthetized decerebrated cats. It is supposed that the depressor response of the arterial pressure depended on the strong cholinergic vasodilatation, reflexively evoked by stimulation of the motor nerve in the intact cats.", "contents": "[Depressor reactions to sural nerve stimulation in intact unanesthetized cats]. Changes in the arterial pressure, in the heart and respiratory rate evoked by the gastrocnemuis nerve stimulation were studied on conscious cats before and during intravenous injection of noradrenaline. Stimulation of the gastrocnemius nerve increased the arterial pressure, the heart and respiratory rates. The same stimulation of the nerve during hypertension caused by noradrenaline injection led to the fall of arterial pressure and tachycardia. The depressor response failed to change under the effect of the beta-adrenoreceptor block and disappeared after the m-cholinoreceptor block with methylatropine. The depressor response was absent in the unanesthetized decerebrated cats. It is supposed that the depressor response of the arterial pressure depended on the strong cholinergic vasodilatation, reflexively evoked by stimulation of the motor nerve in the intact cats."}
{"id": "PMID:192392", "title": "[Concentration of prostaglandins and cyclic adenosine-3',5'-monophosphate in the tissues of rats].", "content": "The content of prostaglandines (PG) and cyclic 3',5'-adenosine monphosphate (cAMP) was investigated in rat tissues by the radioisotopic method of competitive binding. Maximum quantities of both PG and cAMP were revealed in the same most actively functioning organs: the brain, incretory glands, small intestine. Fatty tissue showed minimum quantities of these substances. Results indicate a close functional relationship between the PG synthesis and adenylatecyclase activity in the body tissues.", "contents": "[Concentration of prostaglandins and cyclic adenosine-3',5'-monophosphate in the tissues of rats]. The content of prostaglandines (PG) and cyclic 3',5'-adenosine monphosphate (cAMP) was investigated in rat tissues by the radioisotopic method of competitive binding. Maximum quantities of both PG and cAMP were revealed in the same most actively functioning organs: the brain, incretory glands, small intestine. Fatty tissue showed minimum quantities of these substances. Results indicate a close functional relationship between the PG synthesis and adenylatecyclase activity in the body tissues."}
{"id": "PMID:192393", "title": "[Changes in rat liver mitochondria under conditions of bilateral subdiaphramatic vagotomy].", "content": "A study was made of the changes in the mitochondria of the rat liver under conditions of bilateral subphrenic vagotomy. Two stages in the dynamics of the response of the mitochondrial apparatus to denervation were distingished. During the first stage (0.5-3 days after vagotomy) there occurred reversible functional disturbances of the mitochondria caused by the postoperative stress. The second stage (7 to 60 days after the denervation) was charaterized by more marked structural-functional changes having a number od common features with those seen in hypoxia and being result of vagotomy proper.", "contents": "[Changes in rat liver mitochondria under conditions of bilateral subdiaphramatic vagotomy]. A study was made of the changes in the mitochondria of the rat liver under conditions of bilateral subphrenic vagotomy. Two stages in the dynamics of the response of the mitochondrial apparatus to denervation were distingished. During the first stage (0.5-3 days after vagotomy) there occurred reversible functional disturbances of the mitochondria caused by the postoperative stress. The second stage (7 to 60 days after the denervation) was charaterized by more marked structural-functional changes having a number od common features with those seen in hypoxia and being result of vagotomy proper."}
{"id": "PMID:192394", "title": "[Antiviral activity of preparations of RNA isolated from cells treated with interferon (messenger RNA for an antiviral protein?)].", "content": "Chick embryo cultures treated with interferon yielded a biologically active RNA which, upon inoculation into chick embryo cells, created an antiviral condition in them. The level of vesicular stomatitis virus reproduction in such cells was  2-30% of that observed in the cells treated with control RNA. The maximum activity of the experimental RNA was seen 3 hours after the treatment with interferon.", "contents": "[Antiviral activity of preparations of RNA isolated from cells treated with interferon (messenger RNA for an antiviral protein?)]. Chick embryo cultures treated with interferon yielded a biologically active RNA which, upon inoculation into chick embryo cells, created an antiviral condition in them. The level of vesicular stomatitis virus reproduction in such cells was  2-30% of that observed in the cells treated with control RNA. The maximum activity of the experimental RNA was seen 3 hours after the treatment with interferon."}
{"id": "PMID:192395", "title": "[Electron-cytochemical and morphometric study of the activity of several enzymes in thyrocyte metochondria during malignant degeneration].", "content": "Cytochrome oxidase and succinic dehydrogenase activities were studied in the mitochondria of rat thyroid cell during experimental malignization by means of the electron-cytochemical and morphometric methods. The activity of these enzymes in the mitochondria changed depending on the stage of malignization: at the early stages it approached the normal activity, and at the later stages (precancer)--it decreased and approached the mitochondrial activity of cancer cells. A sharp decrease in the activity of the enzymes under study in the morphologically changed mitochondria of cancer cells may characterize their qualitative changes.", "contents": "[Electron-cytochemical and morphometric study of the activity of several enzymes in thyrocyte metochondria during malignant degeneration]. Cytochrome oxidase and succinic dehydrogenase activities were studied in the mitochondria of rat thyroid cell during experimental malignization by means of the electron-cytochemical and morphometric methods. The activity of these enzymes in the mitochondria changed depending on the stage of malignization: at the early stages it approached the normal activity, and at the later stages (precancer)--it decreased and approached the mitochondrial activity of cancer cells. A sharp decrease in the activity of the enzymes under study in the morphologically changed mitochondria of cancer cells may characterize their qualitative changes."}
{"id": "PMID:192396", "title": "Cyclic 3',5'-adenosine monophosphate level and adenylate cyclase activity in human blood platelets during storage in ACD solution.", "content": "The level of cyclic 3',5'-adenosine monophosphate (cAMP) in human platelets and the activity of platelet adenylate cyclase in response to prostaglandin E1 stimulation do not change during two days storage at room temperature in ACD solution. However, the level of cyclic AMP is lower in platelets stored in ACD solution than in platelets from blood anticoagulated by ethylenediamine tetra-acetic acid.", "contents": "Cyclic 3',5'-adenosine monophosphate level and adenylate cyclase activity in human blood platelets during storage in ACD solution. The level of cyclic 3',5'-adenosine monophosphate (cAMP) in human platelets and the activity of platelet adenylate cyclase in response to prostaglandin E1 stimulation do not change during two days storage at room temperature in ACD solution. However, the level of cyclic AMP is lower in platelets stored in ACD solution than in platelets from blood anticoagulated by ethylenediamine tetra-acetic acid."}
{"id": "PMID:192402", "title": "Profile of beta-adrenoceptors in femoral, superior mesenteric and renal vascular beds of dogs.", "content": "1. The homogeneity of beta-adrenoceptors in femoral, superior mesenteric and renal vascular beds was investigated by the use of the regional perfusion technique in dogs. 2. Isoprenaline and salbutamol produced dose-related increases in femoral and superior mesenteric blood flow. The dose-response curves for the two agonists were parallel, but salbutamol was approximately 1/15 as potent as isoprenaline on a weight basis. 3. Isoprenaline and salbutamol increased renal blood flow in a dose-related manner. However, salbutamol was approximately 1/240 as potent as isoprenaline on a weight basis, and the slope of the dose-response curve for salbutamol was less steep than that for isoprenaline. 4. The dose-response curves to isoprenaline for increase in femoral and superior mesenteric blood flow were shifted to the right by intravenous pindolol but not by intravenous or intra-arterial practolol. 5. The dose-response curves to isoprenaline for increase in renal blood flow were shifted to the right more markedly by intravenous pindolol than by intravenous or intra-arterial practolol. 6. The results indicate that beta-adrenoceptors of the renal vascular bed consist of beta1-type and beta2-type whereas the femoral and superior mesenteric vascular beds contain only beta2-adrenoceptors.", "contents": "Profile of beta-adrenoceptors in femoral, superior mesenteric and renal vascular beds of dogs. 1. The homogeneity of beta-adrenoceptors in femoral, superior mesenteric and renal vascular beds was investigated by the use of the regional perfusion technique in dogs. 2. Isoprenaline and salbutamol produced dose-related increases in femoral and superior mesenteric blood flow. The dose-response curves for the two agonists were parallel, but salbutamol was approximately 1/15 as potent as isoprenaline on a weight basis. 3. Isoprenaline and salbutamol increased renal blood flow in a dose-related manner. However, salbutamol was approximately 1/240 as potent as isoprenaline on a weight basis, and the slope of the dose-response curve for salbutamol was less steep than that for isoprenaline. 4. The dose-response curves to isoprenaline for increase in femoral and superior mesenteric blood flow were shifted to the right by intravenous pindolol but not by intravenous or intra-arterial practolol. 5. The dose-response curves to isoprenaline for increase in renal blood flow were shifted to the right more markedly by intravenous pindolol than by intravenous or intra-arterial practolol. 6. The results indicate that beta-adrenoceptors of the renal vascular bed consist of beta1-type and beta2-type whereas the femoral and superior mesenteric vascular beds contain only beta2-adrenoceptors."}
{"id": "PMID:192405", "title": "Conjugated equine oestrogens and blood clotting: a follow-up report.", "content": "A follow-up study of blood clotting and platelet aggregation was performed on 21 women who had received long-term hormone replacement treatment with conjugated equine oestrogens. The prothrombin time and factor VII and X values were significantly accelerated after three months, but there was no further increase with continual administration for 18 months. After 12 to 18 months' treatment, however, thrombin-induced platelet aggregation (Chandler's tube) was also significantly accelerated, which suggested a widening spectrum of effect. No overall acceleration of \"intrinsic\" clotting (partial thromboplastin time and thromboelastography) was found during the study, but the relatively small numbers may have been responsible. Further efforts are therefore required to find formulations and doses of oestrogens which, while relieving menopausal symptoms, cause less acceleration of blood clotting and platelet aggregation.", "contents": "Conjugated equine oestrogens and blood clotting: a follow-up report. A follow-up study of blood clotting and platelet aggregation was performed on 21 women who had received long-term hormone replacement treatment with conjugated equine oestrogens. The prothrombin time and factor VII and X values were significantly accelerated after three months, but there was no further increase with continual administration for 18 months. After 12 to 18 months' treatment, however, thrombin-induced platelet aggregation (Chandler's tube) was also significantly accelerated, which suggested a widening spectrum of effect. No overall acceleration of \"intrinsic\" clotting (partial thromboplastin time and thromboelastography) was found during the study, but the relatively small numbers may have been responsible. Further efforts are therefore required to find formulations and doses of oestrogens which, while relieving menopausal symptoms, cause less acceleration of blood clotting and platelet aggregation."}
{"id": "PMID:192408", "title": "Plasma immunoreactive corticotrophin and lipotrophin in Cushing's syndrome and Addison's disease.", "content": "Plasma immunoreactive corticotrophin (ACTH) and lipotrophin (LPH) were measured in patients with raised circulating concentrations from a pituitary or an ectopic source. They were measured again in seven patients after they had received hydrocortisone. Plasma ACTH concentrations were higher than LPH concentrations in patients with a pituitary source of their hormones, whereas this relation was reversed when the source was ectopic. After hydrocortisone administration the half life of immunoreactive ACTH was 40 minutes and that of LPH 95 minutes, resulting in a reversal of the normal relation of ACTH to LPH. The use of two antisera with different specificities for measuring LPH has further shown that pituitary LPH differs from ectopic LPH. Relatively less gamma-LPH than beta-LPH was produced from ectopic sources, the relation being reversed in patients with a pituitary source for their raised concentrations. Measuring plasma LPH as well as ACTH might therefore help in deciding whether a patient with Cushing's syndrome has a pituitary or ectopic source of ACTH, which sometimes presents a difficult clinical problem.", "contents": "Plasma immunoreactive corticotrophin and lipotrophin in Cushing's syndrome and Addison's disease. Plasma immunoreactive corticotrophin (ACTH) and lipotrophin (LPH) were measured in patients with raised circulating concentrations from a pituitary or an ectopic source. They were measured again in seven patients after they had received hydrocortisone. Plasma ACTH concentrations were higher than LPH concentrations in patients with a pituitary source of their hormones, whereas this relation was reversed when the source was ectopic. After hydrocortisone administration the half life of immunoreactive ACTH was 40 minutes and that of LPH 95 minutes, resulting in a reversal of the normal relation of ACTH to LPH. The use of two antisera with different specificities for measuring LPH has further shown that pituitary LPH differs from ectopic LPH. Relatively less gamma-LPH than beta-LPH was produced from ectopic sources, the relation being reversed in patients with a pituitary source for their raised concentrations. Measuring plasma LPH as well as ACTH might therefore help in deciding whether a patient with Cushing's syndrome has a pituitary or ectopic source of ACTH, which sometimes presents a difficult clinical problem."}
{"id": "PMID:192412", "title": "Longitudinal fibre splitting in neurogenic muscular disorders--its relation to the pathogenesis of \"myopathic\" change.", "content": "In 15 patients with neurogenic muscular disorders, including cases of motor neuron disease, Wohlfart-Kugelberg-Welander disease, Davidenkow's scapuloperoneal syndrome, peripheral neuropathy and traumatic neuropathies, muscle biopsies were carried out, usually after EMG or single fibre EMG investigation. Enzyme histochemical and electronmicroscopic techniques were used to study longitudinal fibre splitting and its quantitative relation to the general changes in the biopsies. In 9 cases serial sections were used to study the longitudinal extent and character of fibre splitting. Longitudinal fibre splitting was found in 14 cases. It was prominent in Type 1 fibres, and in those biopsies in which hypertrophy was most marked. It was often associated with central migration of sarcolemmal nuclei. Ultrastructurally there was evidence that splitting consisted of mechanical disruption of the myofibrillar pattern, followed by an active process of membrane formation. We suggest that longitudinal splitting of muscle fibres, induced by overload of poorly innervated, hypertrophied fibres, can account for many of the \"myopathic\" changes found in neurogenic muscular disorders.", "contents": "Longitudinal fibre splitting in neurogenic muscular disorders--its relation to the pathogenesis of \"myopathic\" change. In 15 patients with neurogenic muscular disorders, including cases of motor neuron disease, Wohlfart-Kugelberg-Welander disease, Davidenkow's scapuloperoneal syndrome, peripheral neuropathy and traumatic neuropathies, muscle biopsies were carried out, usually after EMG or single fibre EMG investigation. Enzyme histochemical and electronmicroscopic techniques were used to study longitudinal fibre splitting and its quantitative relation to the general changes in the biopsies. In 9 cases serial sections were used to study the longitudinal extent and character of fibre splitting. Longitudinal fibre splitting was found in 14 cases. It was prominent in Type 1 fibres, and in those biopsies in which hypertrophy was most marked. It was often associated with central migration of sarcolemmal nuclei. Ultrastructurally there was evidence that splitting consisted of mechanical disruption of the myofibrillar pattern, followed by an active process of membrane formation. We suggest that longitudinal splitting of muscle fibres, induced by overload of poorly innervated, hypertrophied fibres, can account for many of the \"myopathic\" changes found in neurogenic muscular disorders."}
{"id": "PMID:192413", "title": "The neurological complications of cardiac transplantation.", "content": "Review of the neurological complications encountered in 83 patients who received cardiac homografts over a seven-year period leads to the following conclusions: (1) Neurological disorders are common in transplant recipients, occurring in over 50 per cent of patients. (2) Infection was the single most frequent cause of the neurological dysfunction, being responsible for one-third of all CNS complications. (3) The infective organisms were typically those considered to be usually of low pathogenicity: fungi, viruses, protozoa and an uncommon bacterial strain. (4) Other clinical neurological syndromes were related to vascular lesions, often apparently from cerebral ischaemia or infarction occurring during the surgical procedure, metabolic encephalopathies, cerebral microglioma, acute psychotic episodes and back pain from vertebral compression fractures. (5) The infectious complications and probably the development of neoplasms de novo, are related to immunosuppressive therapy which impairs virtually all host defence mechanisms and alters the nature of the host's response to infective agents or other foreign antigens. (6) Because neurological symptoms and signs were usually those of behavioural changes or deterioration in intellectual performance, the neurological examination was often of little value in diagnosing the nature or even the anatomical site of the neuropathological process. (7) The possibility of an infectious origin of the neurological manifestations must be aggressively pursued even in the absence of fever and a significantly abnormal spinal fluid examination. The diagnostic error made most frequently was to ascribe neurological symptoms erroneously to metabolic disturbances or to \"intensive care unit psychosis\" when they were in fact due to unrecognized CNS infection. (8) Maintenance of mean cardiopulmonary bypass pressures above 70 mmHg, particularly in patients with known arteriosclerosis, may reduce operative morbidity. (9) Though increased diagnostic accuracy is possible with routine use of a variety of radiological and laboratory techniques, two further requirements probably must be met before a significant reduction in the frequency of neurological complications will occur: the advent of greater immunospecificity in suppressing rejection of the grafted organ while preserving defences against infection; and a more effective armamentarium of antiviral and antifungal drugs.", "contents": "The neurological complications of cardiac transplantation. Review of the neurological complications encountered in 83 patients who received cardiac homografts over a seven-year period leads to the following conclusions: (1) Neurological disorders are common in transplant recipients, occurring in over 50 per cent of patients. (2) Infection was the single most frequent cause of the neurological dysfunction, being responsible for one-third of all CNS complications. (3) The infective organisms were typically those considered to be usually of low pathogenicity: fungi, viruses, protozoa and an uncommon bacterial strain. (4) Other clinical neurological syndromes were related to vascular lesions, often apparently from cerebral ischaemia or infarction occurring during the surgical procedure, metabolic encephalopathies, cerebral microglioma, acute psychotic episodes and back pain from vertebral compression fractures. (5) The infectious complications and probably the development of neoplasms de novo, are related to immunosuppressive therapy which impairs virtually all host defence mechanisms and alters the nature of the host's response to infective agents or other foreign antigens. (6) Because neurological symptoms and signs were usually those of behavioural changes or deterioration in intellectual performance, the neurological examination was often of little value in diagnosing the nature or even the anatomical site of the neuropathological process. (7) The possibility of an infectious origin of the neurological manifestations must be aggressively pursued even in the absence of fever and a significantly abnormal spinal fluid examination. The diagnostic error made most frequently was to ascribe neurological symptoms erroneously to metabolic disturbances or to \"intensive care unit psychosis\" when they were in fact due to unrecognized CNS infection. (8) Maintenance of mean cardiopulmonary bypass pressures above 70 mmHg, particularly in patients with known arteriosclerosis, may reduce operative morbidity. (9) Though increased diagnostic accuracy is possible with routine use of a variety of radiological and laboratory techniques, two further requirements probably must be met before a significant reduction in the frequency of neurological complications will occur: the advent of greater immunospecificity in suppressing rejection of the grafted organ while preserving defences against infection; and a more effective armamentarium of antiviral and antifungal drugs."}
{"id": "PMID:192414", "title": "Effects of locus coeruleus lesions upon cerebral monoamine content, sleep-wakefulness states and the response to amphetamine in the cat.", "content": "The purpose of the present study was to investigate the effects of complete lesions of the noradrenaline locus coeruleus neurons upon wakefulness and paradoxical sleep. Radiofrequency lesions of the nucleus were performed in 8 chronically implanted cats which were continuously recorded with an EEG for 5 days prior to and 21 days following the lesions, when they were sacrificed. In 3 of these animals amphetamine (2 mg/kg) was administered on one control day and on the 10th day post-lesion. Following sacrifice, monoamine content was assayed in discrete brain regions, and the lesion was examined in Nissl-stained sections of the pons. (1) The majority (x 69%) of the locus coeruleus was bilaterally destroyed by the lesions which only minimally exceeded the boundaries of the nucleus within the dorsolateral pontine tegmentum. Noradrenaline was depleted by a mean of 85% in the paleo- and neocortex and by a mean of 60% in the thalamus and midbrain. (2) EEG activation reappeared within 12-48 h following the lesion and represented a normal percentage of recording time on the 3rd and subsequent days post-lesion. The behavioral arousal and long-lasting EEG activation produced by amphetamine was qualitatively and quantitatively the same pre- and post-lesion. (3) Despite alteration of certain components, paradoxical sleep reappeared within 48 h and recovered to normal amounts by the second week post-lesion. Muscle atonia was permanently absent in 7 animals. Ponto-geniculo-occipital (PGO) spiking was acutely redistributed across all states and chronically reduced in frequency (by a mean of 50%) within paradoxical sleep. These results indicate that the noradrenaline locus coeruleus neurons are not necessary for the tonic maintenance of EEG activation that occurs in normal wakefulness and in amphetamine-produced arousal. Furthermore, these neurons are not necessary for the occurrence of paradoxical sleep, although they may be involved in modulation of PGO spiking.", "contents": "Effects of locus coeruleus lesions upon cerebral monoamine content, sleep-wakefulness states and the response to amphetamine in the cat. The purpose of the present study was to investigate the effects of complete lesions of the noradrenaline locus coeruleus neurons upon wakefulness and paradoxical sleep. Radiofrequency lesions of the nucleus were performed in 8 chronically implanted cats which were continuously recorded with an EEG for 5 days prior to and 21 days following the lesions, when they were sacrificed. In 3 of these animals amphetamine (2 mg/kg) was administered on one control day and on the 10th day post-lesion. Following sacrifice, monoamine content was assayed in discrete brain regions, and the lesion was examined in Nissl-stained sections of the pons. (1) The majority (x 69%) of the locus coeruleus was bilaterally destroyed by the lesions which only minimally exceeded the boundaries of the nucleus within the dorsolateral pontine tegmentum. Noradrenaline was depleted by a mean of 85% in the paleo- and neocortex and by a mean of 60% in the thalamus and midbrain. (2) EEG activation reappeared within 12-48 h following the lesion and represented a normal percentage of recording time on the 3rd and subsequent days post-lesion. The behavioral arousal and long-lasting EEG activation produced by amphetamine was qualitatively and quantitatively the same pre- and post-lesion. (3) Despite alteration of certain components, paradoxical sleep reappeared within 48 h and recovered to normal amounts by the second week post-lesion. Muscle atonia was permanently absent in 7 animals. Ponto-geniculo-occipital (PGO) spiking was acutely redistributed across all states and chronically reduced in frequency (by a mean of 50%) within paradoxical sleep. These results indicate that the noradrenaline locus coeruleus neurons are not necessary for the tonic maintenance of EEG activation that occurs in normal wakefulness and in amphetamine-produced arousal. Furthermore, these neurons are not necessary for the occurrence of paradoxical sleep, although they may be involved in modulation of PGO spiking."}
{"id": "PMID:192416", "title": "Temporal patterns, their distribution and redundancy in trains of spontaneous neuronal spike intervals of the feline hippocampus studied with a non-parametric technique.", "content": "A modification of the non-parametric technique for the analysis of temporal patterns in long trains of single neuronal spike intervals has been described and tested empiracally. The technique is based on inequality testing of sequential pairs of intervals. If the second interval in a pair is longer or shorter than or equal to the first interval, a(+), a(-), and a (0) is recorded respectively in sequential bins of the computer memory. Subsequently, the long sequences of signs are arranged into transition frequency matrices which are then converted into transition probability matrices of various complexity. In this manner, the sign permutations composed of 4, 5, 6, etc. signs were studied. First of all, the theoretical distribution of various sign permutations was derived, assuming that the arrangement of intervals that generate the signs is totally independent. The theoretical distribution of signs permutations in tetragrams, pentagrams and hexagrams constitute the 'controls' with which the empirical data can be compared. In this manner, using the chi-square test, the total deviation of a studied neuronal output from an independent state can be quantified. The empirical data showed a consistent deviation from the theoretical distribution of sign permutations during REM sleep, as compared to slow wave sleep which was characterized by an almost perfect theoretical distribution of sign permutations. This indicates that slow wave sleep is associated with relaxation of constraints that are responsible for the emergence of specific patterns. In addition, redundancies in the occurrence of sign permutations, and the linear relationships between them, have been defined and tested empirically. The apparent discrepancies between the redundancies, based on theoretical symmetry in sign distribution and the linear redundancy that fits the empirical data, have been defined and discussed.", "contents": "Temporal patterns, their distribution and redundancy in trains of spontaneous neuronal spike intervals of the feline hippocampus studied with a non-parametric technique. A modification of the non-parametric technique for the analysis of temporal patterns in long trains of single neuronal spike intervals has been described and tested empiracally. The technique is based on inequality testing of sequential pairs of intervals. If the second interval in a pair is longer or shorter than or equal to the first interval, a(+), a(-), and a (0) is recorded respectively in sequential bins of the computer memory. Subsequently, the long sequences of signs are arranged into transition frequency matrices which are then converted into transition probability matrices of various complexity. In this manner, the sign permutations composed of 4, 5, 6, etc. signs were studied. First of all, the theoretical distribution of various sign permutations was derived, assuming that the arrangement of intervals that generate the signs is totally independent. The theoretical distribution of signs permutations in tetragrams, pentagrams and hexagrams constitute the 'controls' with which the empirical data can be compared. In this manner, using the chi-square test, the total deviation of a studied neuronal output from an independent state can be quantified. The empirical data showed a consistent deviation from the theoretical distribution of sign permutations during REM sleep, as compared to slow wave sleep which was characterized by an almost perfect theoretical distribution of sign permutations. This indicates that slow wave sleep is associated with relaxation of constraints that are responsible for the emergence of specific patterns. In addition, redundancies in the occurrence of sign permutations, and the linear relationships between them, have been defined and tested empirically. The apparent discrepancies between the redundancies, based on theoretical symmetry in sign distribution and the linear redundancy that fits the empirical data, have been defined and discussed."}
{"id": "PMID:192417", "title": "Ontogeny of beta-adrenergic receptors in rat cerebral cortex.", "content": "The ontogeny of beta-adrenergic receptors in rat cerebral cortex has been studied using [125I]iodohydroxybenzylpindolol as a ligand in an in vitro binding assay. The concentration of beta-adrenergic receptors was very low during the first week after birth. Between days 7 and 14 there was a rapid increase in the density of receptors. Adult levels were reached by the end of the second week. The affinities of 1-isoproterenol and iodohydroxybenzylpindolol for beta-adrenergic receptors did not vary with the age of the animal. Fluoride stimulated adenylate cyclase activity in the cerebral cortex was 40% of the adult level at birth and gradually increased to maximal levels over the next two weeks. On the other hand, catecholamine stimulated cyclic-3',5'-adenosine monophosphate accumulation was barely detectable during the first week after birth, but it increased rapidly to adult levels between days 7 and 14. The results suggest that it is the development of beta-adrenergic receptors that permits the expression of catecholamine sensitive adenylate cyclase activity. Norepinephrine stores in the cerebral cortex developed slowly reaching adult levels approximately two months after birth. There is therefore little correlation between the ontogeny of presynaptic adrenergic nerve terminals and the postsynaptic development of beta-adrenergic receptors.", "contents": "Ontogeny of beta-adrenergic receptors in rat cerebral cortex. The ontogeny of beta-adrenergic receptors in rat cerebral cortex has been studied using [125I]iodohydroxybenzylpindolol as a ligand in an in vitro binding assay. The concentration of beta-adrenergic receptors was very low during the first week after birth. Between days 7 and 14 there was a rapid increase in the density of receptors. Adult levels were reached by the end of the second week. The affinities of 1-isoproterenol and iodohydroxybenzylpindolol for beta-adrenergic receptors did not vary with the age of the animal. Fluoride stimulated adenylate cyclase activity in the cerebral cortex was 40% of the adult level at birth and gradually increased to maximal levels over the next two weeks. On the other hand, catecholamine stimulated cyclic-3',5'-adenosine monophosphate accumulation was barely detectable during the first week after birth, but it increased rapidly to adult levels between days 7 and 14. The results suggest that it is the development of beta-adrenergic receptors that permits the expression of catecholamine sensitive adenylate cyclase activity. Norepinephrine stores in the cerebral cortex developed slowly reaching adult levels approximately two months after birth. There is therefore little correlation between the ontogeny of presynaptic adrenergic nerve terminals and the postsynaptic development of beta-adrenergic receptors."}
{"id": "PMID:192418", "title": "Cyclic AMP-stimulated phosphorylation of a high molecular weight endogenous protein substrate in sub-cellular fractions of molluscan nervous system.", "content": "Cyclic AMP stimulated the incorporation of radioactive phosphate from ATP into endogenous phosphoproteins in a 20,000 X g supernatant, as well as in a 150,000 X g supernatant, prepared from Helix nervous system homogenates. No effect of cyclic AMP was observed in the respective pellet fractions. A part (but not all) of the cyclic AMP-stimulated activity in both supernatants was due to phosphorylation of an endogenous protein substrate, of apparent molecular weight 120,000 daltons as determined from its mobility in polyacrylamide gels. Little phosphorylation of 120,000 dalton material was observed in the particulate fractions, both in the presence and absence of cyclic AMP. When the 20,000 X g pellet was incubated with radioactive ATP and an exogenous calf ovary protein kinase, cyclic AMP stimulated the phosphorylation of the 120,000 dalton material. The results suggest that both membranes and cytosol from Helix nervous system contain 120,000 dalton substrates for cyclic AMP-dependent protein kinase. However, no kinase catalyzing phosphorylation of these substrates is recovered in membrane fractions following homogenization of the tissue.", "contents": "Cyclic AMP-stimulated phosphorylation of a high molecular weight endogenous protein substrate in sub-cellular fractions of molluscan nervous system. Cyclic AMP stimulated the incorporation of radioactive phosphate from ATP into endogenous phosphoproteins in a 20,000 X g supernatant, as well as in a 150,000 X g supernatant, prepared from Helix nervous system homogenates. No effect of cyclic AMP was observed in the respective pellet fractions. A part (but not all) of the cyclic AMP-stimulated activity in both supernatants was due to phosphorylation of an endogenous protein substrate, of apparent molecular weight 120,000 daltons as determined from its mobility in polyacrylamide gels. Little phosphorylation of 120,000 dalton material was observed in the particulate fractions, both in the presence and absence of cyclic AMP. When the 20,000 X g pellet was incubated with radioactive ATP and an exogenous calf ovary protein kinase, cyclic AMP stimulated the phosphorylation of the 120,000 dalton material. The results suggest that both membranes and cytosol from Helix nervous system contain 120,000 dalton substrates for cyclic AMP-dependent protein kinase. However, no kinase catalyzing phosphorylation of these substrates is recovered in membrane fractions following homogenization of the tissue."}
{"id": "PMID:192419", "title": "Distribution of a behaviorally highly potent ACTH4-9 analog in rat brain after intraventricular administration.", "content": "Distribution within the brain of a 3-fold modified ACTH4-9 analog with a remarkably potentiated behavioral activity, 4-MET (O2), 8-d-Lys, 9-Phe-ACTH4-9, was investigated. The radioactive labeled [7-3H-Phe]ACTH4-9 analog was administered intraventricularly in urethane anesthetized rats in a dose of approximately 170 ng. Total radioactivity in CSF, measured in samples drawn from the cisterna magna, decreased over the period of 0.5-4 h after injection from 51 to 2% of the injected dose. Intraventricular injection of the ACTH4-9 analog resulted in high intact peptide levels in the brain. At 2 h after injection the distribution of radioactivity over 2500 micronm and 300 micronm frontal cut brain slices was rather homogenous. Data from distribution studies over topographically defined gross brain structures indicated that the septal area, which is involved in eliciting behavioral activities of ACTH-like neuropeptides, accumulated most of the injected radioactivity per gram wet weight. The distribution profiles within the brain of the [3H]ACTH4-9 analog and [3H]Phe showed considerable differences. Uptake studies in various brain nuclei after intraventricular administration of the [3H]ACTH4-9 analog demonstrated that the greatest part of the investigated nuclei exhibited relative low or medium uptake of radioactivity. This was also true for hippocampal and thalamic nuclei, which have been suggested as effected sites of action for ACTH peptides. Very high accumulation of radioactivity occurred only in the septal nuclei, particularly the dorsal and fimbrial septal nuclei. The results indicate selective uptake of the ACTH4-9 analog in the septal area, suggesting a possible significance of this area as a site of action of ACTH neuro-peptides.", "contents": "Distribution of a behaviorally highly potent ACTH4-9 analog in rat brain after intraventricular administration. Distribution within the brain of a 3-fold modified ACTH4-9 analog with a remarkably potentiated behavioral activity, 4-MET (O2), 8-d-Lys, 9-Phe-ACTH4-9, was investigated. The radioactive labeled [7-3H-Phe]ACTH4-9 analog was administered intraventricularly in urethane anesthetized rats in a dose of approximately 170 ng. Total radioactivity in CSF, measured in samples drawn from the cisterna magna, decreased over the period of 0.5-4 h after injection from 51 to 2% of the injected dose. Intraventricular injection of the ACTH4-9 analog resulted in high intact peptide levels in the brain. At 2 h after injection the distribution of radioactivity over 2500 micronm and 300 micronm frontal cut brain slices was rather homogenous. Data from distribution studies over topographically defined gross brain structures indicated that the septal area, which is involved in eliciting behavioral activities of ACTH-like neuropeptides, accumulated most of the injected radioactivity per gram wet weight. The distribution profiles within the brain of the [3H]ACTH4-9 analog and [3H]Phe showed considerable differences. Uptake studies in various brain nuclei after intraventricular administration of the [3H]ACTH4-9 analog demonstrated that the greatest part of the investigated nuclei exhibited relative low or medium uptake of radioactivity. This was also true for hippocampal and thalamic nuclei, which have been suggested as effected sites of action for ACTH peptides. Very high accumulation of radioactivity occurred only in the septal nuclei, particularly the dorsal and fimbrial septal nuclei. The results indicate selective uptake of the ACTH4-9 analog in the septal area, suggesting a possible significance of this area as a site of action of ACTH neuro-peptides."}
{"id": "PMID:192421", "title": "[The endogenous metabolism of Pseudomonas fluorescens in relation to the oxidation of ethanol, serine, and pyruvate].", "content": "Studies of the oxidation of ethanol, serine and pyruvate by non proliferating suspensions of P. fluorescens show that the rate of oxidation of these substrates is appreciably increased by the addition of NADH. The observed effects are interpreted on the basis of apparent oxidation quotients of NADH which exceed the theoretical values.", "contents": "[The endogenous metabolism of Pseudomonas fluorescens in relation to the oxidation of ethanol, serine, and pyruvate]. Studies of the oxidation of ethanol, serine and pyruvate by non proliferating suspensions of P. fluorescens show that the rate of oxidation of these substrates is appreciably increased by the addition of NADH. The observed effects are interpreted on the basis of apparent oxidation quotients of NADH which exceed the theoretical values."}
{"id": "PMID:192422", "title": "[The effect of previous administration of adrenaline or isoprenaline on the activity of several hypnotics in mice].", "content": "Previous administration of adrenaline (0.5 mg/kg i.p.) and isoprenaline (10 mg/kg i.p.) enhances activity of several hypnotic drugs (pentobarbital, barbital, chloral hydrate) in mice but is without effect upon hypnotic activity of ethanol. This potentialisation is blocked by previous administration of pindolol, but not by phentolamine. Administration of SKF 525 A demonstrates that metabolism of pentobarbital is modified by this enzymatic inhibitor, which is not the case for other hypnotics.", "contents": "[The effect of previous administration of adrenaline or isoprenaline on the activity of several hypnotics in mice]. Previous administration of adrenaline (0.5 mg/kg i.p.) and isoprenaline (10 mg/kg i.p.) enhances activity of several hypnotic drugs (pentobarbital, barbital, chloral hydrate) in mice but is without effect upon hypnotic activity of ethanol. This potentialisation is blocked by previous administration of pindolol, but not by phentolamine. Administration of SKF 525 A demonstrates that metabolism of pentobarbital is modified by this enzymatic inhibitor, which is not the case for other hypnotics."}
{"id": "PMID:192423", "title": "[The effect of some pharmacological agents and electroshock on the level of cyclic AMP of the total mouse brain].", "content": "Amphetamin, pentobarbital, pargyline, parachlorophenylalanine, pentetrasol and maximal electroshock all increased significantly cyclic AMP in mice whole brain conversely reserpine induced a decrease of cyclic nucleotide. All those changes were tentatively correlated toward central monoaminergic systems activation.", "contents": "[The effect of some pharmacological agents and electroshock on the level of cyclic AMP of the total mouse brain]. Amphetamin, pentobarbital, pargyline, parachlorophenylalanine, pentetrasol and maximal electroshock all increased significantly cyclic AMP in mice whole brain conversely reserpine induced a decrease of cyclic nucleotide. All those changes were tentatively correlated toward central monoaminergic systems activation."}
{"id": "PMID:192424", "title": "[A new technic to evaluate the sensitivity of the renal parathyroid hormone receptor in man].", "content": "We propose a simplified assessment of response to parathyroid hormone which could replace the traditional Ellsworth Howard test for the differential diagnosis of pseudohypoparathyroidism in man. We have demonstrated that bovine parathyroid hormone in normal and hypoparathyroid subject increases plasma cAMP except in pseudohypoparathyroid subjects. It is an efficient, reliable method without any collection of urine samples.", "contents": "[A new technic to evaluate the sensitivity of the renal parathyroid hormone receptor in man]. We propose a simplified assessment of response to parathyroid hormone which could replace the traditional Ellsworth Howard test for the differential diagnosis of pseudohypoparathyroidism in man. We have demonstrated that bovine parathyroid hormone in normal and hypoparathyroid subject increases plasma cAMP except in pseudohypoparathyroid subjects. It is an efficient, reliable method without any collection of urine samples."}
{"id": "PMID:192425", "title": "[Immunocytochemical study using semi-thin sections of the phenomena of early differentiation in several cell populations of the human fetal adenohypophysis].", "content": "Immunocytological investigations have been performed on semi-thin sections of human fetal pituitaries ranging in fetal age from 6 to 26 weeks. Corticotrophs can be revealed by anti-ACTH (1-24), anti-ACTH (17-39) and anti-beta MSH but not by anti-alpha MSH immunesera from the 8th week. Somatotrophs are revealed with anti-human STH from 9th week. Differentiating cells containing only alpha subunits of glycoproteic hormones are present from 8th to 12th week. At 13th week beta subunits of TSH can be revealed immunocytologically in thyreotrophs. Beta subunits of LH or FSH can be detected in same gonadotrophic cells only from 15th week.", "contents": "[Immunocytochemical study using semi-thin sections of the phenomena of early differentiation in several cell populations of the human fetal adenohypophysis]. Immunocytological investigations have been performed on semi-thin sections of human fetal pituitaries ranging in fetal age from 6 to 26 weeks. Corticotrophs can be revealed by anti-ACTH (1-24), anti-ACTH (17-39) and anti-beta MSH but not by anti-alpha MSH immunesera from the 8th week. Somatotrophs are revealed with anti-human STH from 9th week. Differentiating cells containing only alpha subunits of glycoproteic hormones are present from 8th to 12th week. At 13th week beta subunits of TSH can be revealed immunocytologically in thyreotrophs. Beta subunits of LH or FSH can be detected in same gonadotrophic cells only from 15th week."}
{"id": "PMID:192426", "title": "Selection of a stable clone of the MVPK-1 fetal porcine kidney cell for assays of foot-and-month disease virus.", "content": "The MVPK-1 cell line, derived from fetal porcine kidney cells, supports the replication of foot-and-mouth disease (FMD) virus. The cell line was adapted to grow in medium containing 5% bovine serum. The susceptibility of the adapted cells decreased as they aged at 37 degrees C. Various clones were isolated from the adapted cells and their growth characteristics and sustained susceptibility to FMD virus were compared. Clone 7 maintained uniform susceptibility to FMD virus over a 3-day period at 37 degrees C and proved superior to other clones in the characteristics studied. The clone has maintained satisfactory susceptibility to FMD virus through 40 subcultures. Clone 7 can replace primary bovine kidney cells for routine viral assays, but cannot detect as much FMD virus in animal specimens as primary bovine kidney, bovine thyroid, or swine kidney cells.", "contents": "Selection of a stable clone of the MVPK-1 fetal porcine kidney cell for assays of foot-and-month disease virus. The MVPK-1 cell line, derived from fetal porcine kidney cells, supports the replication of foot-and-mouth disease (FMD) virus. The cell line was adapted to grow in medium containing 5% bovine serum. The susceptibility of the adapted cells decreased as they aged at 37 degrees C. Various clones were isolated from the adapted cells and their growth characteristics and sustained susceptibility to FMD virus were compared. Clone 7 maintained uniform susceptibility to FMD virus over a 3-day period at 37 degrees C and proved superior to other clones in the characteristics studied. The clone has maintained satisfactory susceptibility to FMD virus through 40 subcultures. Clone 7 can replace primary bovine kidney cells for routine viral assays, but cannot detect as much FMD virus in animal specimens as primary bovine kidney, bovine thyroid, or swine kidney cells."}
{"id": "PMID:192428", "title": "Hypothalamic hypopituitarism after hemiparesis.", "content": "Anterior pituitary insufficiency developed over 15 years in a man who had had a sudden episode of left hemiparesis and slurred speech at the age of 45 years. At age 60 radiographic studies revealed no evidence of a sellar or suprasellar neoplasm, and endocrinologic studies, including stimulation with thyrotropin releasing hormone and luteinizing hormone releasing hormone, yielded results consistent with hypopituitarism of hypothalamic origin. Response to thyroid, adrenocortical and testosterone therapy was good.", "contents": "Hypothalamic hypopituitarism after hemiparesis. Anterior pituitary insufficiency developed over 15 years in a man who had had a sudden episode of left hemiparesis and slurred speech at the age of 45 years. At age 60 radiographic studies revealed no evidence of a sellar or suprasellar neoplasm, and endocrinologic studies, including stimulation with thyrotropin releasing hormone and luteinizing hormone releasing hormone, yielded results consistent with hypopituitarism of hypothalamic origin. Response to thyroid, adrenocortical and testosterone therapy was good."}
{"id": "PMID:192429", "title": "Renal vein plasma adenosine 3',5'-cyclic monophosphate in renovascular hypertension.", "content": "The concentration of plasma adenosine 3',5'-cyclic monophosphate (cyclic AMP) and plasma renin activity (PRA) were measured concomitantly in blood from both renal veins and in arterial blood in 22 hypertensive patients. In the nine patients with true renovascular hypertension the concentration of plasma cyclic AMP was greater in the venous effluent of the kidney affected by the renal artery stenosis than in that of the unaffected or less affected kidney. The arteriovenous difference in cyclic AMP concentration was less on the affected side in all but one patient. The arteriovenous differences in PRA identified the affected kidney as the source of hyper-reninemia and showed that renin release from the other kidney was suppressed. In the 13 patients with hypertension associated with but unrelated to renal artery stenosis there were no consistent patterns of cyclic AMP concentration or PRA in the venous effluent of the kidneys or of their arteriovenous differences. In renovascular hypertension the venous effluent of the kidney affected by renal artery stenosis contains not only more renin but also more cyclic AMP, owing to either increased cyclic AMP production or decreased excretion or extraction of cyclic AMP by the affected kidney.  This unilateral increase in cyclic AMP concentration may become a complementary diagnostic feature of true renovascular hypertension.", "contents": "Renal vein plasma adenosine 3',5'-cyclic monophosphate in renovascular hypertension. The concentration of plasma adenosine 3',5'-cyclic monophosphate (cyclic AMP) and plasma renin activity (PRA) were measured concomitantly in blood from both renal veins and in arterial blood in 22 hypertensive patients. In the nine patients with true renovascular hypertension the concentration of plasma cyclic AMP was greater in the venous effluent of the kidney affected by the renal artery stenosis than in that of the unaffected or less affected kidney. The arteriovenous difference in cyclic AMP concentration was less on the affected side in all but one patient. The arteriovenous differences in PRA identified the affected kidney as the source of hyper-reninemia and showed that renin release from the other kidney was suppressed. In the 13 patients with hypertension associated with but unrelated to renal artery stenosis there were no consistent patterns of cyclic AMP concentration or PRA in the venous effluent of the kidneys or of their arteriovenous differences. In renovascular hypertension the venous effluent of the kidney affected by renal artery stenosis contains not only more renin but also more cyclic AMP, owing to either increased cyclic AMP production or decreased excretion or extraction of cyclic AMP by the affected kidney.  This unilateral increase in cyclic AMP concentration may become a complementary diagnostic feature of true renovascular hypertension."}
{"id": "PMID:192430", "title": "Adjuvant chemotherapy in lung cancer: review and prospects.", "content": "The results of trials testing combined surgery and chemotherapy in lung cancer are reviewed. Fifteen adjuvant trials using various chemotherapeutic agents were analyzed to determine reasons for their lack of success. Current trials with adjuvant therapy in lung cancer are briefly outlined. In addition, analysis of the activity of chemotherapeutic agents in advanced lung cancer and its implications in the design of future adjuvant studies are detailed.", "contents": "Adjuvant chemotherapy in lung cancer: review and prospects. The results of trials testing combined surgery and chemotherapy in lung cancer are reviewed. Fifteen adjuvant trials using various chemotherapeutic agents were analyzed to determine reasons for their lack of success. Current trials with adjuvant therapy in lung cancer are briefly outlined. In addition, analysis of the activity of chemotherapeutic agents in advanced lung cancer and its implications in the design of future adjuvant studies are detailed."}
{"id": "PMID:192431", "title": "Intrahepatic arterial infusion of combination of mitomycin-C and 5-fluorouracil in treatment of primary and metastatic liver carcinoma.", "content": "Improvement in drug response and reduction of toxicity were observed after continuous intrahepatic arterial infusion of mytomycin-C (MMC) and 5-fluorouracil (5-FU) in 15 of 26 patients with primary or metastatic carcinoma of the liver. Serum bilirubin values of 10 mg/100 ml absence of ascites, extreme cachexia and impending hepatic failure were used as the criteria for admission of these patients into the study. The patients were given MMC in a dose of 0.08 mg/kg on day 1,5-FU in a dose of 8-10 mg/kg on days 2-5, and MMC on day 6. This schedule was reinitiated on days 8 and 15 for total mean duration of 18 days. Maintenance therapy was carried out by the administration of these drugs at induction dosage alternated each week as a single 24 hourly intravenous infusion. Objective response to combination therapy was defined as decrease of at least 50% in the liver size and in the abnormal levels of serum alkaline phosphatase and glutamic oxaloacetic transaminase (SGOT), and near normal levels of serum bilirubin for a minimum period of 2 months. The duration of objective response ranged from 3-16 months with a median of 8.2 months. The median survival time for the responders was 7.2 months for patients with primary carcinoma and 9.4 months for patients with metastatic carcinoma of the liver as compared to 2 months for patients who failed to respond to the treatment. Five out of 12 patients who were refractory to MMC or 5-FU by intravenous infusion responded to the present combination drug therapy. Of four patients who died during induction therapy, three had liver failure and the fourth suffered pulmonary embolism. These studies provide evidence that combination therapy with MMC and 5-FU increases the survival time of patients with hepatic cancer, presumably due to the synergistic action of these drugs which permits the use of a low dosage schedule and has less toxic effects.", "contents": "Intrahepatic arterial infusion of combination of mitomycin-C and 5-fluorouracil in treatment of primary and metastatic liver carcinoma. Improvement in drug response and reduction of toxicity were observed after continuous intrahepatic arterial infusion of mytomycin-C (MMC) and 5-fluorouracil (5-FU) in 15 of 26 patients with primary or metastatic carcinoma of the liver. Serum bilirubin values of 10 mg/100 ml absence of ascites, extreme cachexia and impending hepatic failure were used as the criteria for admission of these patients into the study. The patients were given MMC in a dose of 0.08 mg/kg on day 1,5-FU in a dose of 8-10 mg/kg on days 2-5, and MMC on day 6. This schedule was reinitiated on days 8 and 15 for total mean duration of 18 days. Maintenance therapy was carried out by the administration of these drugs at induction dosage alternated each week as a single 24 hourly intravenous infusion. Objective response to combination therapy was defined as decrease of at least 50% in the liver size and in the abnormal levels of serum alkaline phosphatase and glutamic oxaloacetic transaminase (SGOT), and near normal levels of serum bilirubin for a minimum period of 2 months. The duration of objective response ranged from 3-16 months with a median of 8.2 months. The median survival time for the responders was 7.2 months for patients with primary carcinoma and 9.4 months for patients with metastatic carcinoma of the liver as compared to 2 months for patients who failed to respond to the treatment. Five out of 12 patients who were refractory to MMC or 5-FU by intravenous infusion responded to the present combination drug therapy. Of four patients who died during induction therapy, three had liver failure and the fourth suffered pulmonary embolism. These studies provide evidence that combination therapy with MMC and 5-FU increases the survival time of patients with hepatic cancer, presumably due to the synergistic action of these drugs which permits the use of a low dosage schedule and has less toxic effects."}
{"id": "PMID:192432", "title": "Malignant (fibrous) histiocytoma of bone--fact or fancy?.", "content": "Malignant (fibrous) histiocytoma is currently defined as a malignant primary bone tumor that contains a mixture of fibrogenic cells and cells that are histologically similar but which appear to be histiocytic. In this type of histiocytoma the nuclei are often indented; cytoplasm is usually abundant and may be slightly foamy; nucleoli are often large; and multinucleated malignant cells are usually a prominent feature. Many dedifferentiated chondrosarcomas, osteosarcomas, and fibrosarcomas of bone contain areas that resemble what we regard as malignant (fibrous) histiocytoma. When the entirety of a malignant tumor of bone fits the outlined histologic pattern, the designation of malignant (fibrous) histiocytoma seems appropriate. From 158 fibrosarcomas of bone and 962 osteosarcomas of bone in our files, 35 tumors were segregated because they appeared to be properly designated as malignant (fibrous) histiocytoma. A wide age range was represented by affected patients, and a large variety of bones harbored these tumors. Approximately one-third of patients eligible for 5-year follow-up were long-term, symptom-free survivors. Four deaths occurred from the tumor after more than 5 years, and one patient had radiographic evidence of pulmonary metastasis 7 years after amputation. Radiation therapy has been curative in at least two cases. The correct designation for these tumors in the light of current knowledge is malignant tumor, consistent with malignant (fibrous) histiocytoma.", "contents": "Malignant (fibrous) histiocytoma of bone--fact or fancy?. Malignant (fibrous) histiocytoma is currently defined as a malignant primary bone tumor that contains a mixture of fibrogenic cells and cells that are histologically similar but which appear to be histiocytic. In this type of histiocytoma the nuclei are often indented; cytoplasm is usually abundant and may be slightly foamy; nucleoli are often large; and multinucleated malignant cells are usually a prominent feature. Many dedifferentiated chondrosarcomas, osteosarcomas, and fibrosarcomas of bone contain areas that resemble what we regard as malignant (fibrous) histiocytoma. When the entirety of a malignant tumor of bone fits the outlined histologic pattern, the designation of malignant (fibrous) histiocytoma seems appropriate. From 158 fibrosarcomas of bone and 962 osteosarcomas of bone in our files, 35 tumors were segregated because they appeared to be properly designated as malignant (fibrous) histiocytoma. A wide age range was represented by affected patients, and a large variety of bones harbored these tumors. Approximately one-third of patients eligible for 5-year follow-up were long-term, symptom-free survivors. Four deaths occurred from the tumor after more than 5 years, and one patient had radiographic evidence of pulmonary metastasis 7 years after amputation. Radiation therapy has been curative in at least two cases. The correct designation for these tumors in the light of current knowledge is malignant tumor, consistent with malignant (fibrous) histiocytoma."}
{"id": "PMID:192433", "title": "The changing histopathology of lung cancer: a review of 1682 cases.", "content": "We have reviewed the histopathology of lung cancer patients seen over the past 13 years at RPMI. Assessment of this data indicates that adenocarcinoma is becoming progressively more prevalent as related to the other forms of lung cancer. Factors which in part may account for this increased prevalence are: 1) changes in criteria for reading histopathology of lung cancer, particularly since 1967; 2) the increased incidence of lung cancer among the female population who have a propensity for adenocarcinoma; and 3) occupational and environmental factors. In 1974 adenocarcinoma for the first time became the most prevalent type of lung cancer at RPMI. Whatever the reason, if our data are truly representative of a national trend, adenocarcinoma will soon become the most prevalent type of lung cancer in the United States. This fact may result in an increasing death rate since the present 18-month survival rate for adenocarcinoma is substantially less than for squamous cell carcinoma, which has in the past been the prevalent form of the disease. As the smoking habits of women more closely approximate those of men, we expect that the incidence and mortality of lung cancer will prove to be quite similar in both sexes.", "contents": "The changing histopathology of lung cancer: a review of 1682 cases. We have reviewed the histopathology of lung cancer patients seen over the past 13 years at RPMI. Assessment of this data indicates that adenocarcinoma is becoming progressively more prevalent as related to the other forms of lung cancer. Factors which in part may account for this increased prevalence are: 1) changes in criteria for reading histopathology of lung cancer, particularly since 1967; 2) the increased incidence of lung cancer among the female population who have a propensity for adenocarcinoma; and 3) occupational and environmental factors. In 1974 adenocarcinoma for the first time became the most prevalent type of lung cancer at RPMI. Whatever the reason, if our data are truly representative of a national trend, adenocarcinoma will soon become the most prevalent type of lung cancer in the United States. This fact may result in an increasing death rate since the present 18-month survival rate for adenocarcinoma is substantially less than for squamous cell carcinoma, which has in the past been the prevalent form of the disease. As the smoking habits of women more closely approximate those of men, we expect that the incidence and mortality of lung cancer will prove to be quite similar in both sexes."}
{"id": "PMID:192434", "title": "Myxoid variant of malignant fibrous histiocytoma.", "content": "It has been generally recognized that malignant fibrous histiocytoma (MFH) may assume a highly myxoid, hypocellular appearance. Eighty cases of malignant fibrous histiocytoma having varying degrees of myxoid change were reviewed. These tumors typically arose on the extremities (leg, 61%; arm, 21%) of adults (peak age incidence, 60-69 years). They were usually attached to fascia (31%) or involved skeletal muscle (51%) and had a mucoid or translucent appearance. The myxoid areas consisted of widely spaced spindled and pleomorphic cells embedded in a matrix of acid mucopolysaccharides. The cellular areas were indistinguishable from those of the typical pleomorphic MFH. The rate of local recurrence of these tumors was 61%, and of metastasis, 23%, but metastasis was less likely when the tumor was small, superficially located, or had a prominent myxoid component. In fact, the degree of myxoid change was inversely related to the rate of metastasis. Therefore, because of the more favorable prognosis of the myxoid variant, it seems appropriate to separate it from the usual nonmyxoid form of MFH. The myxoid variant must also be clearly distinguished from benign myxoid lesions such as myxoma or nodular fasciitis, with which it is often confused.", "contents": "Myxoid variant of malignant fibrous histiocytoma. It has been generally recognized that malignant fibrous histiocytoma (MFH) may assume a highly myxoid, hypocellular appearance. Eighty cases of malignant fibrous histiocytoma having varying degrees of myxoid change were reviewed. These tumors typically arose on the extremities (leg, 61%; arm, 21%) of adults (peak age incidence, 60-69 years). They were usually attached to fascia (31%) or involved skeletal muscle (51%) and had a mucoid or translucent appearance. The myxoid areas consisted of widely spaced spindled and pleomorphic cells embedded in a matrix of acid mucopolysaccharides. The cellular areas were indistinguishable from those of the typical pleomorphic MFH. The rate of local recurrence of these tumors was 61%, and of metastasis, 23%, but metastasis was less likely when the tumor was small, superficially located, or had a prominent myxoid component. In fact, the degree of myxoid change was inversely related to the rate of metastasis. Therefore, because of the more favorable prognosis of the myxoid variant, it seems appropriate to separate it from the usual nonmyxoid form of MFH. The myxoid variant must also be clearly distinguished from benign myxoid lesions such as myxoma or nodular fasciitis, with which it is often confused."}
{"id": "PMID:192435", "title": "Diet and cancer.", "content": "Differences in food intake patterns are positively correlated with differences in the incidence of various cancers in world populations. It is postulated here that dietary factors play a vital role in the genesis of several major neoplasms, specifically gastric and colon carcinomas. In addition to the food consumed, such variables as total caloric intake, nutrtional excess or deficit, exposure to carcinogens and consumption of alcohol also increase the risk of cancer. Through recognition of these factors and subsequent long-term manipulation of diet, it should be possible to reduce cancer morbidity and mortality.", "contents": "Diet and cancer. Differences in food intake patterns are positively correlated with differences in the incidence of various cancers in world populations. It is postulated here that dietary factors play a vital role in the genesis of several major neoplasms, specifically gastric and colon carcinomas. In addition to the food consumed, such variables as total caloric intake, nutrtional excess or deficit, exposure to carcinogens and consumption of alcohol also increase the risk of cancer. Through recognition of these factors and subsequent long-term manipulation of diet, it should be possible to reduce cancer morbidity and mortality."}
{"id": "PMID:192436", "title": "Immunodiagnostic potential of a virus-coded, tumor-associated antigen (AG-4) in cervical cancer.", "content": "The central theme of this communication is the recognition of an immunodiagnostic potential in a herpes virus antigen, the molecular interrelationship of which with cervical tumor cells is described. In addition to the productive infection caused by herpes simplex virus type 2 (HSV-2) we are confronted by latency and, as suggested by recent studies, by cancer. These different types of virus-host cell interactions are discussed at the host, as well as at the cellular level. A defined level of molecular interaction between host and viral gene products must exist if the virus is to co-exist with the host, as is the case in latency and carcinogenesis. The molecular interpretations posit the presence, in the squamous cervical tumor cells, of a product of the expression of the viral genome that has immunodiagnostic potential. The antigen designated AG-4 fulfills these predictions and appears to have immunodiagnostic potential. AG-4 is present in cervical tumor biopsies, but not in normal cervical tissue. It is a structural component of the HSV-2 virion that, in tissue cultures infected with HSV-2, is synthesized preferentially under conditions that prevent the normal replication of the virus. In view of its structural nature it is most probably virus-coded. AG-4 antibody identified in complement fixation assays with antigen prepared in tissue culture, disappears following successful tumor removal and reappears during cancer recurrence. This antibody also potentially identifies those patients with cervical atypia that are at high risk of neoplastic progression. The clinical benefits of the assay are evident.", "contents": "Immunodiagnostic potential of a virus-coded, tumor-associated antigen (AG-4) in cervical cancer. The central theme of this communication is the recognition of an immunodiagnostic potential in a herpes virus antigen, the molecular interrelationship of which with cervical tumor cells is described. In addition to the productive infection caused by herpes simplex virus type 2 (HSV-2) we are confronted by latency and, as suggested by recent studies, by cancer. These different types of virus-host cell interactions are discussed at the host, as well as at the cellular level. A defined level of molecular interaction between host and viral gene products must exist if the virus is to co-exist with the host, as is the case in latency and carcinogenesis. The molecular interpretations posit the presence, in the squamous cervical tumor cells, of a product of the expression of the viral genome that has immunodiagnostic potential. The antigen designated AG-4 fulfills these predictions and appears to have immunodiagnostic potential. AG-4 is present in cervical tumor biopsies, but not in normal cervical tissue. It is a structural component of the HSV-2 virion that, in tissue cultures infected with HSV-2, is synthesized preferentially under conditions that prevent the normal replication of the virus. In view of its structural nature it is most probably virus-coded. AG-4 antibody identified in complement fixation assays with antigen prepared in tissue culture, disappears following successful tumor removal and reappears during cancer recurrence. This antibody also potentially identifies those patients with cervical atypia that are at high risk of neoplastic progression. The clinical benefits of the assay are evident."}
{"id": "PMID:192437", "title": "The epidemiology of the feline leukemia virus (FeLV).", "content": "Clustering of cases of feline lymphosarcoma (LSA) has been observed by veterinarians for many years. In 1964 it was discovered that feline LSA was caused by an oncornavirus, the feline leukemia virus (FeLV). In 1970, a simple, indirect immunoflourescent antibody (IFA) test for FeLV was developed which enabled large numbers of cats, living in their natural (household) environments, to be tested for the virus. In one study, over 2,000 cats were tested and the results showed conclusively that FeLV is a contagious agent for cats. This finding was independently confirmed by several other investigators using different testing procedures. After discovering the contagious nature of FeLV a test and removal program was devised which successfully prevents the spread of FeLV and the development of FeLV diseases in the pet cat population. There is, at present, no evidence that FeLV infects humans living with FeLV infected cats.", "contents": "The epidemiology of the feline leukemia virus (FeLV). Clustering of cases of feline lymphosarcoma (LSA) has been observed by veterinarians for many years. In 1964 it was discovered that feline LSA was caused by an oncornavirus, the feline leukemia virus (FeLV). In 1970, a simple, indirect immunoflourescent antibody (IFA) test for FeLV was developed which enabled large numbers of cats, living in their natural (household) environments, to be tested for the virus. In one study, over 2,000 cats were tested and the results showed conclusively that FeLV is a contagious agent for cats. This finding was independently confirmed by several other investigators using different testing procedures. After discovering the contagious nature of FeLV a test and removal program was devised which successfully prevents the spread of FeLV and the development of FeLV diseases in the pet cat population. There is, at present, no evidence that FeLV infects humans living with FeLV infected cats."}
{"id": "PMID:192438", "title": "Cancer induction by exogenous hormones: possible androgen-induced cancer.", "content": "Since 1973, there has been an increase in the reported number of cases of liver tumors (both benign and malignant), associated with the intake of male hormones as anabolic steroids and oral contraceptives. Because these tumors are very rare in the younger age groups, and because there are approximately 50 million women taking oral contraceptives at the present time, there is a definite need for a large-scale epidemiological investigation to clarify this possible association.", "contents": "Cancer induction by exogenous hormones: possible androgen-induced cancer. Since 1973, there has been an increase in the reported number of cases of liver tumors (both benign and malignant), associated with the intake of male hormones as anabolic steroids and oral contraceptives. Because these tumors are very rare in the younger age groups, and because there are approximately 50 million women taking oral contraceptives at the present time, there is a definite need for a large-scale epidemiological investigation to clarify this possible association."}
{"id": "PMID:192439", "title": "Venereal factors in human cervical cancer: evidence from marital clusters.", "content": "All Caucasian women in a large Eastern city who developed pathologically confirmed cervical cancer between 1950 and 1969 are being prospectively followed in an epidemiological test of the venereal hypothesis of cervical carcinogenesis. We are attempting to identify all men who were married to these probands at any time prior to the date of their cancer diagnosis. The ultimate objective is the identification of all the other wives of the proband husbands in order that their risk of cervical cancer be assessed. A random sample of control wives similar to the other wives in age, race, date and place of marriage as well as prior marital status is also being followed. To date, a total of 1,087 other wives and 659 control wives has been fully traced. Cervical cancer or carcinoma in situ was detected in 29 (2.7%) of the other wives and in seven (1.1%) of the control wives. A total of 14.0% of the other wives had either cervical cancer or a cervical cytological specimen which was other than normal. The corresponding statistic for the control wives was 8.0%. These differences in the prevalence of cervical cancer and of non-normal cervical cytology are statistically significant. In the course of this investigation so far, we have identified 29 \"marital clusters\" of cervical cancer in which two women married to the same man have all developed cervical neoplasms. The observed number of 29 clusters may be compared with an expected number of 11.6. This investigation, as yet incomplete, offers confirmatory evidence of the possible role of venereal factors in the pathogenesis of human cervical neoplasia. While the genital herpesvirus is the likeliest candidate, other venereal elements might also be involved.", "contents": "Venereal factors in human cervical cancer: evidence from marital clusters. All Caucasian women in a large Eastern city who developed pathologically confirmed cervical cancer between 1950 and 1969 are being prospectively followed in an epidemiological test of the venereal hypothesis of cervical carcinogenesis. We are attempting to identify all men who were married to these probands at any time prior to the date of their cancer diagnosis. The ultimate objective is the identification of all the other wives of the proband husbands in order that their risk of cervical cancer be assessed. A random sample of control wives similar to the other wives in age, race, date and place of marriage as well as prior marital status is also being followed. To date, a total of 1,087 other wives and 659 control wives has been fully traced. Cervical cancer or carcinoma in situ was detected in 29 (2.7%) of the other wives and in seven (1.1%) of the control wives. A total of 14.0% of the other wives had either cervical cancer or a cervical cytological specimen which was other than normal. The corresponding statistic for the control wives was 8.0%. These differences in the prevalence of cervical cancer and of non-normal cervical cytology are statistically significant. In the course of this investigation so far, we have identified 29 \"marital clusters\" of cervical cancer in which two women married to the same man have all developed cervical neoplasms. The observed number of 29 clusters may be compared with an expected number of 11.6. This investigation, as yet incomplete, offers confirmatory evidence of the possible role of venereal factors in the pathogenesis of human cervical neoplasia. While the genital herpesvirus is the likeliest candidate, other venereal elements might also be involved."}
{"id": "PMID:192440", "title": "Oral fluorouracil therapy of hepatoma.", "content": "Oral fluorouracil was administered weekly to 12 consecutive patients with unresectable hepatoma. Six patients showed an objective response with a significant increase in survival duration compared to nonresponders and to untreated patients. The clinical features of these cases are discussed, along with details of therapy, and possible reasons for the encouraging results noted with this treatment regimen.", "contents": "Oral fluorouracil therapy of hepatoma. Oral fluorouracil was administered weekly to 12 consecutive patients with unresectable hepatoma. Six patients showed an objective response with a significant increase in survival duration compared to nonresponders and to untreated patients. The clinical features of these cases are discussed, along with details of therapy, and possible reasons for the encouraging results noted with this treatment regimen."}
{"id": "PMID:192441", "title": "5-Flourouracil in hepatocellular carcinoma: report of twenty-one cases.", "content": "Twenty-one patients with biopsy-proven hepatocellular carcinoma were treated with oral or intravenous 5-Fluorouracil according to a randomized treatment schedule. Twenty-one patients were evaluable for response and toxicity. The two groups were comparable in distribution of pretreatment characteristics. There were no objective responses in either group. This is the largest reported group of patients with hepatocellular carcinoma treated with 5-Fluorouracil. Toxicity occurred in 46% of patients treated, but was tolerable. In contrast to previous reports, we have found that weekly 5-Fluorouracil given orally or intravenously is not of significant value in the treatment of hepatocellular carcinoma.", "contents": "5-Flourouracil in hepatocellular carcinoma: report of twenty-one cases. Twenty-one patients with biopsy-proven hepatocellular carcinoma were treated with oral or intravenous 5-Fluorouracil according to a randomized treatment schedule. Twenty-one patients were evaluable for response and toxicity. The two groups were comparable in distribution of pretreatment characteristics. There were no objective responses in either group. This is the largest reported group of patients with hepatocellular carcinoma treated with 5-Fluorouracil. Toxicity occurred in 46% of patients treated, but was tolerable. In contrast to previous reports, we have found that weekly 5-Fluorouracil given orally or intravenously is not of significant value in the treatment of hepatocellular carcinoma."}
{"id": "PMID:192442", "title": "Combination chemotherapy for small cell carcinoma of the lung.", "content": "Sixty-one patients with proven small cell carcinoma of the bronchus were treated by a five-drug pulsed chemotherapy schedule involving cyclophosphamide, vincristine, Adriamycin, methotrexate and prednisolone, given at four-week intervals. The response rate was 60%. All patients also received radiotherapy (4000-5000 rad) to the primary lesion. Survival was identical whether radiotherapy was given first or between the second and third courses of chemotherapy. The survival of responding patients was significantly prolonged as compared both with the non-responders in this series and with a similar group of patients treated only by radiotherapy in this hospital in 1970. The poor results in patients resistant to chemotherapy reflect the fact that 88% of the patients had disseminated disease at the time of diagnosis. The survival of responding patients was not improved over that reported by others as a result of incorporating Adriamycin and prednisolone into the schedule, so there seems no justification for using them in future treatments based on this pattern of chemotherapy. It was possible to identify all responding patients within six weeks of initiating chemotherapy, and a delay of this duration did not affect the efficacy of radiotherapy. Radiotherapy, however, frequently interfered with the subsequent assessment of response to chemotherapy. It therefore seems obligatory to give chemotherapy before radiotherapy in order to determine which patients will benefit from subsequent drug treatment.", "contents": "Combination chemotherapy for small cell carcinoma of the lung. Sixty-one patients with proven small cell carcinoma of the bronchus were treated by a five-drug pulsed chemotherapy schedule involving cyclophosphamide, vincristine, Adriamycin, methotrexate and prednisolone, given at four-week intervals. The response rate was 60%. All patients also received radiotherapy (4000-5000 rad) to the primary lesion. Survival was identical whether radiotherapy was given first or between the second and third courses of chemotherapy. The survival of responding patients was significantly prolonged as compared both with the non-responders in this series and with a similar group of patients treated only by radiotherapy in this hospital in 1970. The poor results in patients resistant to chemotherapy reflect the fact that 88% of the patients had disseminated disease at the time of diagnosis. The survival of responding patients was not improved over that reported by others as a result of incorporating Adriamycin and prednisolone into the schedule, so there seems no justification for using them in future treatments based on this pattern of chemotherapy. It was possible to identify all responding patients within six weeks of initiating chemotherapy, and a delay of this duration did not affect the efficacy of radiotherapy. Radiotherapy, however, frequently interfered with the subsequent assessment of response to chemotherapy. It therefore seems obligatory to give chemotherapy before radiotherapy in order to determine which patients will benefit from subsequent drug treatment."}
{"id": "PMID:192443", "title": "Malignant mixed tumors arising in salivary glands. I. Carcinomas arising in benign mixed tumors: a clinicopathologic study.", "content": "Forty-seven cases of malignant mixed tumor (MMT) arising in major and minor salivary glands are presented. By definition, all these lesions contained both a benign mixed tumor (BMT) as well as a malignant neoplasm, usually a poorly differentiated carcinoma. In some cases, the carcinoma developed in a previously untreated salivary gland mass which was known to have been present for many years, others evolved in a recurrent previously resected BMT and still others originated in a previously undetected BMT. Adverse prognostic factors included: carcinomatous involvement of the resection lines, perineural invasion, metastases in lymph nodes, and origin in a major salivary gland. Lesions arising in the palate had a better prognosis as compared to major salivary gland tumors. Some patients died of locally uncontrollable tumor and others because of metastatic disease. Local recurrences of MMT were seen frequently; 18 patients (38%) had a total of 32 local recurrences. Of patients followed five years or more, seven (35%) had died of tumor, 11 (55%) had no evidence of disease, and two (10%) had died of other causes. Prolonged follow-up is required because recurrences and death from tumor may be seen many years following the diagnosis of MMT. Recommendations for therapy are made. Criteria for differentiating MMT from recurrent BMT and from cylindromatous carcinoma are discussed.", "contents": "Malignant mixed tumors arising in salivary glands. I. Carcinomas arising in benign mixed tumors: a clinicopathologic study. Forty-seven cases of malignant mixed tumor (MMT) arising in major and minor salivary glands are presented. By definition, all these lesions contained both a benign mixed tumor (BMT) as well as a malignant neoplasm, usually a poorly differentiated carcinoma. In some cases, the carcinoma developed in a previously untreated salivary gland mass which was known to have been present for many years, others evolved in a recurrent previously resected BMT and still others originated in a previously undetected BMT. Adverse prognostic factors included: carcinomatous involvement of the resection lines, perineural invasion, metastases in lymph nodes, and origin in a major salivary gland. Lesions arising in the palate had a better prognosis as compared to major salivary gland tumors. Some patients died of locally uncontrollable tumor and others because of metastatic disease. Local recurrences of MMT were seen frequently; 18 patients (38%) had a total of 32 local recurrences. Of patients followed five years or more, seven (35%) had died of tumor, 11 (55%) had no evidence of disease, and two (10%) had died of other causes. Prolonged follow-up is required because recurrences and death from tumor may be seen many years following the diagnosis of MMT. Recommendations for therapy are made. Criteria for differentiating MMT from recurrent BMT and from cylindromatous carcinoma are discussed."}
{"id": "PMID:192444", "title": "Massive infantile nephroblastomatosis: a clinical, radiological, and pathological analysis of four cases.", "content": "Four cases of massive infantile nephroblastomatosis with up to three and one-half years follow-up are described. Great similarity was found clinically, radiologically and pathologically, which distinguishes this entity from true Wilms' tumor. The course of the renal lesion following treatment was monitored by sequential radiological and biopsy studies. The pathogenesis, natural history, and management are discussed.", "contents": "Massive infantile nephroblastomatosis: a clinical, radiological, and pathological analysis of four cases. Four cases of massive infantile nephroblastomatosis with up to three and one-half years follow-up are described. Great similarity was found clinically, radiologically and pathologically, which distinguishes this entity from true Wilms' tumor. The course of the renal lesion following treatment was monitored by sequential radiological and biopsy studies. The pathogenesis, natural history, and management are discussed."}
{"id": "PMID:192445", "title": "Comparison of nuclear nonhistone phosphoproteins of rat liver and Novikoff hepatoma.", "content": "As part of a continuing comparison of nuclear proteins of tumors and other tissues, 32P-labeled nuclear proteins were extracted successively with 0.15 and 0.35 m NaC1 from the nuclei of normal, regenerating, and thioacetamide-treated rat liver as well as Novikoff hepatoma 3 hr after injection of 32Pi into rats. Separation of proteins of these fractions with aqueous phenol was carried out before two-dimensional electrophoresis on polyacrylamide gels. By autoradiography many common spots were found, but four 32P-labeled protein spots, CU', C13p, C21p, and CMp, were found in the Novikoff hepatoma and not in the various liver samples studied. Two spots, B6 and B10, were found in the liver patterns and not in the tumor. Sot B33 was very dense in regenerating liver but was only a faint spot in thioacetamide-treated liver. The greater density of Spots CU', C13p, C21p, and CMp in the tumor patterns is consistent with the increased density reported earlier for spots of the C-region of a variety of tumors.", "contents": "Comparison of nuclear nonhistone phosphoproteins of rat liver and Novikoff hepatoma. As part of a continuing comparison of nuclear proteins of tumors and other tissues, 32P-labeled nuclear proteins were extracted successively with 0.15 and 0.35 m NaC1 from the nuclei of normal, regenerating, and thioacetamide-treated rat liver as well as Novikoff hepatoma 3 hr after injection of 32Pi into rats. Separation of proteins of these fractions with aqueous phenol was carried out before two-dimensional electrophoresis on polyacrylamide gels. By autoradiography many common spots were found, but four 32P-labeled protein spots, CU', C13p, C21p, and CMp, were found in the Novikoff hepatoma and not in the various liver samples studied. Two spots, B6 and B10, were found in the liver patterns and not in the tumor. Sot B33 was very dense in regenerating liver but was only a faint spot in thioacetamide-treated liver. The greater density of Spots CU', C13p, C21p, and CMp in the tumor patterns is consistent with the increased density reported earlier for spots of the C-region of a variety of tumors."}
{"id": "PMID:192446", "title": "Specific non-immunoglobulin G antibodies and cell-mediated response to herpes simplex virus antigens in women with cervical carcinoma.", "content": "Non-immunoglobulin G-neutralizing antibodies to herpes simplex virus (HSV) type 2 were assayed in sera adsorbed with Staphylococcus aureus Cowan I. They were present in 8% of women with normal cervical smear and in 20, 41, and 74% of women with atypia, dysplasia, and cervical carcinoma, respectively. Lymphocytes of the patients were tested for in vitro transformation by killed HSV type 1 and HSV type 2 (HSV-2), as well as by mitomycin C-treated hamster cells transformed by HSV or other viruses or not transformed. Specific stimulation by the HSV-transformed cells occurred in 2, 22, and 40% of women with normal cervical smear, dysplasia, and carcinoma of the cervix, respectively. This frequency rose to 82% during treatment with irradiation and decreased to 0% after surgery. When HSV-2 virions were used as antigens to stimulate the lymphocytes, similar differences were found between the various groups, but they were less clear-cut, since 16% of the control women had lymphocytes responding to HSV. Non-immunoglobulin G antibodies to HSV-2 were not present in blood at the same time as cell response to HSV-2-transformed cells. There was also a negative correlation between neutralizing activities of the sera and the indices of lymphocyte stimulation, indicating a regulation between humoral and cell-mediated responses.", "contents": "Specific non-immunoglobulin G antibodies and cell-mediated response to herpes simplex virus antigens in women with cervical carcinoma. Non-immunoglobulin G-neutralizing antibodies to herpes simplex virus (HSV) type 2 were assayed in sera adsorbed with Staphylococcus aureus Cowan I. They were present in 8% of women with normal cervical smear and in 20, 41, and 74% of women with atypia, dysplasia, and cervical carcinoma, respectively. Lymphocytes of the patients were tested for in vitro transformation by killed HSV type 1 and HSV type 2 (HSV-2), as well as by mitomycin C-treated hamster cells transformed by HSV or other viruses or not transformed. Specific stimulation by the HSV-transformed cells occurred in 2, 22, and 40% of women with normal cervical smear, dysplasia, and carcinoma of the cervix, respectively. This frequency rose to 82% during treatment with irradiation and decreased to 0% after surgery. When HSV-2 virions were used as antigens to stimulate the lymphocytes, similar differences were found between the various groups, but they were less clear-cut, since 16% of the control women had lymphocytes responding to HSV. Non-immunoglobulin G antibodies to HSV-2 were not present in blood at the same time as cell response to HSV-2-transformed cells. There was also a negative correlation between neutralizing activities of the sera and the indices of lymphocyte stimulation, indicating a regulation between humoral and cell-mediated responses."}
{"id": "PMID:192447", "title": "Association of the glycolipid pattern with antigenic alterations in mouse fibroblasts transformed by murine sarcoma virus.", "content": "The level of the neutral glycolipid, Galnac beta 1 leads to 4 Gal beta 1 leads to 4Glc leads to Cer (asialo GM2), in BALB/c 3T3 mouse fibroblasts transformed by Kirsten murine sarcoma virus (3T3KIMSV) was greatly increased compared to the nontransformed parental cells (3T3). This elevated chemical quantity was found to be localized on the surface of intact cells and accessible to external reagents, as detected by immunofluorescence and labeling with galactose oxidase: NaB3H4. Furthermore, immunization of rabbits with 3T3KiMSV cells but not with 3T3 cells resulted in antibody production against asialo GM2. These results demonstrate the potential usefulness of glycolipids as tumor-associated cell surface markers.", "contents": "Association of the glycolipid pattern with antigenic alterations in mouse fibroblasts transformed by murine sarcoma virus. The level of the neutral glycolipid, Galnac beta 1 leads to 4 Gal beta 1 leads to 4Glc leads to Cer (asialo GM2), in BALB/c 3T3 mouse fibroblasts transformed by Kirsten murine sarcoma virus (3T3KIMSV) was greatly increased compared to the nontransformed parental cells (3T3). This elevated chemical quantity was found to be localized on the surface of intact cells and accessible to external reagents, as detected by immunofluorescence and labeling with galactose oxidase: NaB3H4. Furthermore, immunization of rabbits with 3T3KiMSV cells but not with 3T3 cells resulted in antibody production against asialo GM2. These results demonstrate the potential usefulness of glycolipids as tumor-associated cell surface markers."}
{"id": "PMID:192448", "title": "Effect of tumor promoters on the activity of cyclic adenosine 3':5'-monophosphate-dependent and -independent protein kinases from mouse epidermis.", "content": "Cyclic adenosine 3'5'-monophosphate (cyclic AMP)-dependent and -independent protein kinases were detected and partially characterized in soluble extracts from mouse epidermis. Cylic AMP-dependent histone kinase activity was separated rom cyclic AMP-independent casein kinase activity by DEAE-Sephadex chromatography. The application of the tumor promoters croton oil or 12-o-tetradecanoyl-phorbol-13-acetate to mouse skin caused a rapid increase in the soluble protein extractable from the epidermis resulting in a decrease in the specific activity of both classes of protein kinase when expressed on a protein basis. No change in the activities of either the cyclic AMP-dependent or -independent enzymes was observed when expressed relative to the DNA content.", "contents": "Effect of tumor promoters on the activity of cyclic adenosine 3':5'-monophosphate-dependent and -independent protein kinases from mouse epidermis. Cyclic adenosine 3'5'-monophosphate (cyclic AMP)-dependent and -independent protein kinases were detected and partially characterized in soluble extracts from mouse epidermis. Cylic AMP-dependent histone kinase activity was separated rom cyclic AMP-independent casein kinase activity by DEAE-Sephadex chromatography. The application of the tumor promoters croton oil or 12-o-tetradecanoyl-phorbol-13-acetate to mouse skin caused a rapid increase in the soluble protein extractable from the epidermis resulting in a decrease in the specific activity of both classes of protein kinase when expressed on a protein basis. No change in the activities of either the cyclic AMP-dependent or -independent enzymes was observed when expressed relative to the DNA content."}
{"id": "PMID:192449", "title": "Investigation of the rate-determining microsomal reaction of cholesterol biosynthesis from lanosterol in Morris hepatomas and liver.", "content": "Previously, we reported that the properties or microsomal 4-methyl sterol demethylase isolated from liver and Morris hepatomas 5123C and 7777 are grossly similar. The individual enzymic steps of this multicomponent system have now been studied, and the rate-determining step has been determined and shown to be identical for liver and these hepatomas. The rates of microsomal oxidative attacks of the 4alpha-methyl, 4alpha-hydroxymethyl, and 4-aldehydic groups are similar for microsomes prepared from rat liver and hepatoma 7777. The rates of mixed-function oxidative attack appear to increase in the order;--CH3 less than --CH2OH less than --CHO. Furthermore, the hepatic and hepatoma NAD-dependent decarboxylase, which catalyzes the reaction following the three oxidative attacks is similar in properties and velocity. The fifth step, an NADPH-dependent reduction of the 3 ketosteroid that is produced by decarboxylation, is also similar. For both tissues, the latter two reactions, under in vitro conditions, proceed at rates that exceed the initial oxidative process. Thus, for elimination of both of the 4-methyl groups of lanosterol, the 10 individual reactions catalyzed in this multicomponent system are identical in liver and hepatoma 7777 microsomes, and the rate-determining stop for both liver and hepatoma is the inital oxidative attack on the 4alpha-methyl group of cholesterol procursors. When the rate-determining reaction of both liver and hepatoma 7777 microsomes is assayed at different temperatures, the same activation energies and the same characteristic breaks in the arrhenius plots are observed. Thus, for both liver and hepatoma, both the nature and the site of rate determination in this multienzymic system must be similar. Since the microsomal enzymes of liver nad hepatoma appear to be catalytically similar and rate determination appears to be similar, too, the characteristic lact of response of tumor microsomes to treatments in vivo that alter host liver microsomal demethylation activity suggests that the insensitivity of these tumors to dietary cholesterol should not be ascribed to alterations in the catalytic proteins. Evidence in this report suggests that the postmicrosomal supernatant fraction of both liver and hepatoma contains a cytosolic protein that may participate in the regulation of the rate-determining attack of 4alpha-methyl sterol substrates. Thus, either qualitative or quantitative differences between the postmicrosomal supernatant fractions obtained from liver and heptomas may account for the observed differences in rates of cholesterol biosynthesis.", "contents": "Investigation of the rate-determining microsomal reaction of cholesterol biosynthesis from lanosterol in Morris hepatomas and liver. Previously, we reported that the properties or microsomal 4-methyl sterol demethylase isolated from liver and Morris hepatomas 5123C and 7777 are grossly similar. The individual enzymic steps of this multicomponent system have now been studied, and the rate-determining step has been determined and shown to be identical for liver and these hepatomas. The rates of microsomal oxidative attacks of the 4alpha-methyl, 4alpha-hydroxymethyl, and 4-aldehydic groups are similar for microsomes prepared from rat liver and hepatoma 7777. The rates of mixed-function oxidative attack appear to increase in the order;--CH3 less than --CH2OH less than --CHO. Furthermore, the hepatic and hepatoma NAD-dependent decarboxylase, which catalyzes the reaction following the three oxidative attacks is similar in properties and velocity. The fifth step, an NADPH-dependent reduction of the 3 ketosteroid that is produced by decarboxylation, is also similar. For both tissues, the latter two reactions, under in vitro conditions, proceed at rates that exceed the initial oxidative process. Thus, for elimination of both of the 4-methyl groups of lanosterol, the 10 individual reactions catalyzed in this multicomponent system are identical in liver and hepatoma 7777 microsomes, and the rate-determining stop for both liver and hepatoma is the inital oxidative attack on the 4alpha-methyl group of cholesterol procursors. When the rate-determining reaction of both liver and hepatoma 7777 microsomes is assayed at different temperatures, the same activation energies and the same characteristic breaks in the arrhenius plots are observed. Thus, for both liver and hepatoma, both the nature and the site of rate determination in this multienzymic system must be similar. Since the microsomal enzymes of liver nad hepatoma appear to be catalytically similar and rate determination appears to be similar, too, the characteristic lact of response of tumor microsomes to treatments in vivo that alter host liver microsomal demethylation activity suggests that the insensitivity of these tumors to dietary cholesterol should not be ascribed to alterations in the catalytic proteins. Evidence in this report suggests that the postmicrosomal supernatant fraction of both liver and hepatoma contains a cytosolic protein that may participate in the regulation of the rate-determining attack of 4alpha-methyl sterol substrates. Thus, either qualitative or quantitative differences between the postmicrosomal supernatant fractions obtained from liver and heptomas may account for the observed differences in rates of cholesterol biosynthesis."}
{"id": "PMID:192450", "title": "Effect of inhibiting DNA, RNA, and protein synthesis of tumor cells on their susceptibility to killing by antibody and complement.", "content": "A number of metabolic inhibitors and chemotherapeutic agents have been found to increase the sensitivity of a chemically induced guinea pig hepatoma (line 1) to killing by antibody and complement. We have investigated whether the mechanism whereby these drugs increase sensitivity to killing is attributable to their primary action of inhibiting DNA, RNA, or protein synthesis. Line 1 cells incubated for 1, 4, or 17 hr with actinomycin D (25 microng/ml), adriamycin (40 microng/ml), or puromycin (5 micron/ml) or with 5-fold lower concentrations of these drugs were maximally inhibited (greater than 90%) in their ability to synthesize DNA, RNA, and protein within 1 hr. However, only cells incubated for 17 hr with the high concentrations of drugs showed increased sensitivity to killing by antibody and complement. Line 1 cells incubated with high concentrations of these drugs of 17 hr, washed, and resuspended in drug-free medium recovered their resistance to killing by antibody and complement within 4 hr. These cells ever after culture for 24 hr in drug-free medium did not regain their ability to synthesize DNA, RNA, or protein. A similar lack of correlation between synthesis of these macromolecules and sensitivity to antibody-complement-mediated killing was observed after the cells were treated with physical agents that inhibit macromolecular synthesis. Both heat-treated and X-irradiated cells were inhibited in their ability to synthesize DNA, RNA, and protein immediately after treatment; however, only X-irradiated cells (6 and 16 hr postirradiation) were increased in their sensitivity to antibody-complement-mediated killing. Our data show that the ability of line 1 tumor cells to resist humoral immune attack does not depend solely on their ability to synthesize DNA, RNA, or protein.", "contents": "Effect of inhibiting DNA, RNA, and protein synthesis of tumor cells on their susceptibility to killing by antibody and complement. A number of metabolic inhibitors and chemotherapeutic agents have been found to increase the sensitivity of a chemically induced guinea pig hepatoma (line 1) to killing by antibody and complement. We have investigated whether the mechanism whereby these drugs increase sensitivity to killing is attributable to their primary action of inhibiting DNA, RNA, or protein synthesis. Line 1 cells incubated for 1, 4, or 17 hr with actinomycin D (25 microng/ml), adriamycin (40 microng/ml), or puromycin (5 micron/ml) or with 5-fold lower concentrations of these drugs were maximally inhibited (greater than 90%) in their ability to synthesize DNA, RNA, and protein within 1 hr. However, only cells incubated for 17 hr with the high concentrations of drugs showed increased sensitivity to killing by antibody and complement. Line 1 cells incubated with high concentrations of these drugs of 17 hr, washed, and resuspended in drug-free medium recovered their resistance to killing by antibody and complement within 4 hr. These cells ever after culture for 24 hr in drug-free medium did not regain their ability to synthesize DNA, RNA, or protein. A similar lack of correlation between synthesis of these macromolecules and sensitivity to antibody-complement-mediated killing was observed after the cells were treated with physical agents that inhibit macromolecular synthesis. Both heat-treated and X-irradiated cells were inhibited in their ability to synthesize DNA, RNA, and protein immediately after treatment; however, only X-irradiated cells (6 and 16 hr postirradiation) were increased in their sensitivity to antibody-complement-mediated killing. Our data show that the ability of line 1 tumor cells to resist humoral immune attack does not depend solely on their ability to synthesize DNA, RNA, or protein."}
{"id": "PMID:192451", "title": "Procedures for radioimmunoassay of the mouse mammary tumor virus.", "content": "A procedure for radioimmunoassay of the major glycoprotein antigen derived from murine mammary tumor virus is described. The assay is sensitive to 0.05 ng of antigen and is highly reproducible. The antigen, gp55, has been found to be group specific and will detect viruses in 13 separate mouse strains, as wel  .l as from continuous cell lines. Factors affecting the assay have been examined.", "contents": "Procedures for radioimmunoassay of the mouse mammary tumor virus. A procedure for radioimmunoassay of the major glycoprotein antigen derived from murine mammary tumor virus is described. The assay is sensitive to 0.05 ng of antigen and is highly reproducible. The antigen, gp55, has been found to be group specific and will detect viruses in 13 separate mouse strains, as wel  .l as from continuous cell lines. Factors affecting the assay have been examined."}
{"id": "PMID:192452", "title": "Cross-neutralization of ovine and bovine C-type leukemia virus-induced syncytia formation.", "content": "Ovine leukemia virus (OLV) could not be distinguished from bovine leukemia virus (BLV) morphologically. Both C-type RNA tumor virus-producing cells induced syncytia when cocultivated with several indicator cells including XC and KC cells. Syncytia formation could be blocked by antibodies against OLV and BLV, indicating that fusion was virus mediated. Furthermore, antibodies against OLV and BLV exhibited reciprocal syncytial blocking properties, suggesting that OLV and BLV were closely related viruses.", "contents": "Cross-neutralization of ovine and bovine C-type leukemia virus-induced syncytia formation. Ovine leukemia virus (OLV) could not be distinguished from bovine leukemia virus (BLV) morphologically. Both C-type RNA tumor virus-producing cells induced syncytia when cocultivated with several indicator cells including XC and KC cells. Syncytia formation could be blocked by antibodies against OLV and BLV, indicating that fusion was virus mediated. Furthermore, antibodies against OLV and BLV exhibited reciprocal syncytial blocking properties, suggesting that OLV and BLV were closely related viruses."}
{"id": "PMID:192453", "title": "Glycosyltransferases and glycosidases in Morris hepatomas.", "content": "The following three parameters were studied in Morris hepatomas of different growth rates: (a) the specific activity of guanosine dephosphate (GDP)-fucose:glycoprotein fucosyltransferase and cytidine monophosphate (CMP)-N-acetylneuraminic acid:glycoprotein sialyltransferase, (B) the content of GDP-fucosee and CMP-N-acetylneuraminic acid, and (c) the activity of alpha-L-fucosidase and neuraminidase. Fucosyltrasferase activities were significantly elevated in all hepatomas investigated. Especially high levels of enzyme were measured in the rapidly growing tumors 7777, 66, and 3924A. The increase varied between 2- and 3-fold when compared with the corresponding host liver. Conversely, the activity of the sialytransferase was greatly decreased in all hepatoma lines with a rapid or intermediate growth rate. In the fast-growing tumor 9618A2, the activity was reduced to 8%. GDP-fucose and CMP-N-acetylneuraminic acid were determined by the isotope dilution technique. In normal rat liver from Buffalo or ACl rats, the concentration of GDP-fucose was 6.5+/-0.9 and 9.5+/-1.1nmoles/g, wet weight, respectively. In the fast-growing hepatomas 3924A and 9121, levels up to 21.5 nmoles/g, wet weight, were found, However, the content of CMP-N-acetylneuraminic acid in hepatomas was indluenced to a lesser extent by the degree of differentiation of the tumor. In the most rapidly growing tumor, 9618A2, a level of alpha-L- fucosidase seven times higher than in host liver was determined. Moreover, there existed a correlation bewteen the age of the hepatoma and enzyme activity. Within the 2nd week after inoculation, fucosidase activity increased from 130 to 343 nmoles/hr/mg of protein. Neuraminidase was measured in a new linked assay system. The activity of this enzyme was lowered by 50% or was at least unchanged when compared to the activity in host liver. Our results indicate that specific alterations of fucose metabolism are a characteristic feature of Morris hepatomas.", "contents": "Glycosyltransferases and glycosidases in Morris hepatomas. The following three parameters were studied in Morris hepatomas of different growth rates: (a) the specific activity of guanosine dephosphate (GDP)-fucose:glycoprotein fucosyltransferase and cytidine monophosphate (CMP)-N-acetylneuraminic acid:glycoprotein sialyltransferase, (B) the content of GDP-fucosee and CMP-N-acetylneuraminic acid, and (c) the activity of alpha-L-fucosidase and neuraminidase. Fucosyltrasferase activities were significantly elevated in all hepatomas investigated. Especially high levels of enzyme were measured in the rapidly growing tumors 7777, 66, and 3924A. The increase varied between 2- and 3-fold when compared with the corresponding host liver. Conversely, the activity of the sialytransferase was greatly decreased in all hepatoma lines with a rapid or intermediate growth rate. In the fast-growing tumor 9618A2, the activity was reduced to 8%. GDP-fucose and CMP-N-acetylneuraminic acid were determined by the isotope dilution technique. In normal rat liver from Buffalo or ACl rats, the concentration of GDP-fucose was 6.5+/-0.9 and 9.5+/-1.1nmoles/g, wet weight, respectively. In the fast-growing hepatomas 3924A and 9121, levels up to 21.5 nmoles/g, wet weight, were found, However, the content of CMP-N-acetylneuraminic acid in hepatomas was indluenced to a lesser extent by the degree of differentiation of the tumor. In the most rapidly growing tumor, 9618A2, a level of alpha-L- fucosidase seven times higher than in host liver was determined. Moreover, there existed a correlation bewteen the age of the hepatoma and enzyme activity. Within the 2nd week after inoculation, fucosidase activity increased from 130 to 343 nmoles/hr/mg of protein. Neuraminidase was measured in a new linked assay system. The activity of this enzyme was lowered by 50% or was at least unchanged when compared to the activity in host liver. Our results indicate that specific alterations of fucose metabolism are a characteristic feature of Morris hepatomas."}
{"id": "PMID:192454", "title": "Elevated expression of T-antigen in simian papovavirus 40-infected skin fibroblasts from individuals with cytogenetic defects.", "content": "A number of cytogenetic conditions were examined for expression of simian papovavirus 40 T-antigen in vitro. Skin fibroblasts from patients with Turner's syndrome and trisomy 18 syndrome and most cell lines from Klinefelter's syndrome, trisomy 13 syndrome, chromosomal translocations, chromosome 21 deletions, and single cases of 18q- and 4p- exhibited elevated T-antigen expression, compared to a clinically and cytogenetically normal control population. Thus, T-antigen expression was generally elevated in cells with increased, decreased, or rearranged genetic material involving many different chromosomes. Variation in T-antigen expression among cell lines may reflect two factors. Individual cell line factors may account for differences within homogeneous clinical groups, whereas population factors appear to account for differences between the various clinical groups and the control population. The observation of elevated T-antigen expression in diverse cytogenetic conditions suggests that this phenomenon may be a manifestation of chromosomal aberration unrelated to cancer susceptibility.", "contents": "Elevated expression of T-antigen in simian papovavirus 40-infected skin fibroblasts from individuals with cytogenetic defects. A number of cytogenetic conditions were examined for expression of simian papovavirus 40 T-antigen in vitro. Skin fibroblasts from patients with Turner's syndrome and trisomy 18 syndrome and most cell lines from Klinefelter's syndrome, trisomy 13 syndrome, chromosomal translocations, chromosome 21 deletions, and single cases of 18q- and 4p- exhibited elevated T-antigen expression, compared to a clinically and cytogenetically normal control population. Thus, T-antigen expression was generally elevated in cells with increased, decreased, or rearranged genetic material involving many different chromosomes. Variation in T-antigen expression among cell lines may reflect two factors. Individual cell line factors may account for differences within homogeneous clinical groups, whereas population factors appear to account for differences between the various clinical groups and the control population. The observation of elevated T-antigen expression in diverse cytogenetic conditions suggests that this phenomenon may be a manifestation of chromosomal aberration unrelated to cancer susceptibility."}
{"id": "PMID:192455", "title": "Characterization of pyrimidine nucleoside monophosphokinase in normal and malignant tissues.", "content": "It was found that there are two kinds of pyrimidine nucleoside, monophosphokinase deoxythymidine 5'-monophosphate-deoxyuridine 5'-monophosphate (dTMP-dUMP) kinase and cytidine 5'-monophosphate-deoxycytidine 5'-monophosphate-uridine 5'-monophosphate-doexyuridine 5'-monophosphate (CMP-dCMP-UMP-dUMP) kinase, and their molecular weights were calculated to be 46,000 and 26,000, respectively, by gel filtration. dTMP-dUMP kinase phosphorylated dTMP with a Km of 3.1 X 10(-5)M and dUMP with a Km of 7.7 X 10(-4) M. dTMP phosphorylation catalyzed by dTMP-dUMP kinase was inhibited competively by dUMP with a Ki of 2.0 X 10(-3) M. Similarly, phosphorylation of dUMP by this enzyme was inhibited competively by dTMP with a Ki of 2.5 X 10 (-5) M. CMP-dCMP-UMP-dUMP kinase of Yoshida sarcoma phosphorylated dUMP with a Km of 3.1 X 10(-3) M and dCMP with a Km of 7.1 X 10 (-4) M, but it did not phosphorylate dTMP. Phosphorylation of dUMP BY CMP-dCMP-UMP-dUMP kinase was inhibited competitively by DCMP and dTMP with Ki's of 6.9 X 10(-4) and 3.0 X 10(-3) M, respectively, and phosphorylation of dCMP was inhibited completely by dUMP a Ki of 2.2 X 10(-3) M. Relative Vmax activity of this enzyme was 345 nmoles/mg protein with dCMP and 127 nmoles/mg protein with dUMP.", "contents": "Characterization of pyrimidine nucleoside monophosphokinase in normal and malignant tissues. It was found that there are two kinds of pyrimidine nucleoside, monophosphokinase deoxythymidine 5'-monophosphate-deoxyuridine 5'-monophosphate (dTMP-dUMP) kinase and cytidine 5'-monophosphate-deoxycytidine 5'-monophosphate-uridine 5'-monophosphate-doexyuridine 5'-monophosphate (CMP-dCMP-UMP-dUMP) kinase, and their molecular weights were calculated to be 46,000 and 26,000, respectively, by gel filtration. dTMP-dUMP kinase phosphorylated dTMP with a Km of 3.1 X 10(-5)M and dUMP with a Km of 7.7 X 10(-4) M. dTMP phosphorylation catalyzed by dTMP-dUMP kinase was inhibited competively by dUMP with a Ki of 2.0 X 10(-3) M. Similarly, phosphorylation of dUMP by this enzyme was inhibited competively by dTMP with a Ki of 2.5 X 10 (-5) M. CMP-dCMP-UMP-dUMP kinase of Yoshida sarcoma phosphorylated dUMP with a Km of 3.1 X 10(-3) M and dCMP with a Km of 7.1 X 10 (-4) M, but it did not phosphorylate dTMP. Phosphorylation of dUMP BY CMP-dCMP-UMP-dUMP kinase was inhibited competitively by DCMP and dTMP with Ki's of 6.9 X 10(-4) and 3.0 X 10(-3) M, respectively, and phosphorylation of dCMP was inhibited completely by dUMP a Ki of 2.2 X 10(-3) M. Relative Vmax activity of this enzyme was 345 nmoles/mg protein with dCMP and 127 nmoles/mg protein with dUMP."}
{"id": "PMID:192456", "title": "Estrogen receptors in androgen-induced breast tumor regression.", "content": "The hormone-dependent 7,12-dimethylbenz(a)anthracene rat mammary tumor has been shown to regress when administered pharmacological doses of testosterone propionate. Tumor regression was correlated with estrogen receptor before and 15 to 20 days following testosterone therapy. A dramatic decline of receptor occurred in all regressing tumors, whereas those administered sesame oil alone maintained both growth and receptor content. Although receptor in regressing tumor was significantly less than in the untreated biopsies, the small amount of remaining receptor maintained the same binding affinity to estradiol, showing that testosterone affects the number and not estrogen affinity of the estrogen receptor. These studies suggest that testosterone depletion of estrogen receptor may be causally related to tumor regression.", "contents": "Estrogen receptors in androgen-induced breast tumor regression. The hormone-dependent 7,12-dimethylbenz(a)anthracene rat mammary tumor has been shown to regress when administered pharmacological doses of testosterone propionate. Tumor regression was correlated with estrogen receptor before and 15 to 20 days following testosterone therapy. A dramatic decline of receptor occurred in all regressing tumors, whereas those administered sesame oil alone maintained both growth and receptor content. Although receptor in regressing tumor was significantly less than in the untreated biopsies, the small amount of remaining receptor maintained the same binding affinity to estradiol, showing that testosterone affects the number and not estrogen affinity of the estrogen receptor. These studies suggest that testosterone depletion of estrogen receptor may be causally related to tumor regression."}
{"id": "PMID:192457", "title": "Influence of age at inoculation on avian oncornavirus-induced brain tumor incidence, tumor morphology, and postinoculation survival in F344 rats.", "content": "Intracranial neoplasms were induced by intracerebral inoculation of a standardized, cell-free inoculum of the Bratislava-77 strain of avian sarcoma virus in F344 rats at 1, 9,97 to 99, and 528 days of age. Deaths from diseases that occur spontaneously in aged F344 rats complicated assessment of tumor incidence in rats inoculated at 528 days; 20 of 30 rats inoculated at this age developed brain tumors. All rats inoculated at age 1 day (47 rats), at age 9 days (37 rats), and at 97 to 99 days of age (41 rats) developed brain tumors. The incidence of animals developing tumors was 100% in these three groups, but the incidence of multiple tumors declined with increasing age at inoculation. The mean and variance of postinoculation survival increased from 83.8 +/- 21.5 days for rats inoculated at 1 day of age to 284.6 +/- 151.5 days for rats inoculated at 97 to 99 days of age. Poorly differentiated astrocytomas and astrocytomas of mixed morphology were common among rats inoculated as neonates. Solitary, pilocytic astrocytomas were the most common tumors among rats inoculated as adults.", "contents": "Influence of age at inoculation on avian oncornavirus-induced brain tumor incidence, tumor morphology, and postinoculation survival in F344 rats. Intracranial neoplasms were induced by intracerebral inoculation of a standardized, cell-free inoculum of the Bratislava-77 strain of avian sarcoma virus in F344 rats at 1, 9,97 to 99, and 528 days of age. Deaths from diseases that occur spontaneously in aged F344 rats complicated assessment of tumor incidence in rats inoculated at 528 days; 20 of 30 rats inoculated at this age developed brain tumors. All rats inoculated at age 1 day (47 rats), at age 9 days (37 rats), and at 97 to 99 days of age (41 rats) developed brain tumors. The incidence of animals developing tumors was 100% in these three groups, but the incidence of multiple tumors declined with increasing age at inoculation. The mean and variance of postinoculation survival increased from 83.8 +/- 21.5 days for rats inoculated at 1 day of age to 284.6 +/- 151.5 days for rats inoculated at 97 to 99 days of age. Poorly differentiated astrocytomas and astrocytomas of mixed morphology were common among rats inoculated as neonates. Solitary, pilocytic astrocytomas were the most common tumors among rats inoculated as adults."}
{"id": "PMID:192458", "title": "Comparison of the blood supply to diethylnitrosamine-induced hyperplastic nodules and hepatomas and to the surrounding liver.", "content": "Intravascular injection of radionuclide-labeled microspheres was used to compare the blood supply to diethylnitrosamine-induced hyperplastic liver nodules and hepatomas with the blood supply to the surrounding, histologically normal liver. Microspheres injected into the heart or portal vein lodged in the organs of control and diethylnitrosamine-treated rats providing a quantitative index of blood supply to the microvascular bed. The blood supply is expressed as percentage of cardiac output (arterial) or cpm (portal) per organ, lobe, g tissue, etc. The fraction of the cardiac output received by lung, kidneys, spleen, and liver was similar in control and carcinogen-treated animals. The arterial blood supply of 23 nodules and hepatomas was variable [1.17 +/- 0.22% (S.E.) cardiac output per g, fixed weight], but it was similar to the arterial supply to the surrounding tissue (1.12 +/- 0.21% cardiac output per g, fixed weight). In contrast the portal blood supply to 25 selected lesions wa 39 +/- 6% that of the surrounding liver tissue. There was no apparent relationship between blood supply and lesion size or histological appearance. While only 0.13 +/- 0.04% of the microspheres injected via the portal system were recovered in the lungs of control rats, approximately 100 times this number bypassed or escaped the liver containing nodules and hepatomas and lodged in the lungs. Such alterations in blood flow could contribute to biological diversification of hepatic lesions in successive stages of cancer evolution and could facilitate metastasis from the liver.", "contents": "Comparison of the blood supply to diethylnitrosamine-induced hyperplastic nodules and hepatomas and to the surrounding liver. Intravascular injection of radionuclide-labeled microspheres was used to compare the blood supply to diethylnitrosamine-induced hyperplastic liver nodules and hepatomas with the blood supply to the surrounding, histologically normal liver. Microspheres injected into the heart or portal vein lodged in the organs of control and diethylnitrosamine-treated rats providing a quantitative index of blood supply to the microvascular bed. The blood supply is expressed as percentage of cardiac output (arterial) or cpm (portal) per organ, lobe, g tissue, etc. The fraction of the cardiac output received by lung, kidneys, spleen, and liver was similar in control and carcinogen-treated animals. The arterial blood supply of 23 nodules and hepatomas was variable [1.17 +/- 0.22% (S.E.) cardiac output per g, fixed weight], but it was similar to the arterial supply to the surrounding tissue (1.12 +/- 0.21% cardiac output per g, fixed weight). In contrast the portal blood supply to 25 selected lesions wa 39 +/- 6% that of the surrounding liver tissue. There was no apparent relationship between blood supply and lesion size or histological appearance. While only 0.13 +/- 0.04% of the microspheres injected via the portal system were recovered in the lungs of control rats, approximately 100 times this number bypassed or escaped the liver containing nodules and hepatomas and lodged in the lungs. Such alterations in blood flow could contribute to biological diversification of hepatic lesions in successive stages of cancer evolution and could facilitate metastasis from the liver."}
{"id": "PMID:192459", "title": "DNA transfection of ecotropic murine leukemia viruses in mouse cell cultures.", "content": "DNA's were isolated from cells chronically infected with N-, B-, or NB-tropic murine leukemia viruses and tested for infectious activity in various mouse cell cultures. Early detection of the DNA transfection is facilitated by growing the DNA-recipient cells in medium containing 10(-6) M hydrocortisone. Appropriate shearing of the DNA preparations may increase the efficiency of the transfection. With these procedures virus production of the transfected cells can be detected by XC plaque assay as early as 4 days after DNA inoculation in NIH 3T3 cells. Susceptibility of the mouse cell cultures to DNA transfection does not parallel their susceptibility to virion infection. Progeny viruses derived from the transfection show the same N- or B-tropic host range property as do the parent viruses.", "contents": "DNA transfection of ecotropic murine leukemia viruses in mouse cell cultures. DNA's were isolated from cells chronically infected with N-, B-, or NB-tropic murine leukemia viruses and tested for infectious activity in various mouse cell cultures. Early detection of the DNA transfection is facilitated by growing the DNA-recipient cells in medium containing 10(-6) M hydrocortisone. Appropriate shearing of the DNA preparations may increase the efficiency of the transfection. With these procedures virus production of the transfected cells can be detected by XC plaque assay as early as 4 days after DNA inoculation in NIH 3T3 cells. Susceptibility of the mouse cell cultures to DNA transfection does not parallel their susceptibility to virion infection. Progeny viruses derived from the transfection show the same N- or B-tropic host range property as do the parent viruses."}
{"id": "PMID:192460", "title": "Elevated concentration of a dexamethasone-receptor translocation inhibitor in Novikoff hepatoma cells.", "content": "Despite the apparent similarity of the dexamethasone-receptor concentration in the rat liver and Novikoff hepatoma cytoplasms, the in vitro translocation of the dexamethasone-receptor complex into liver or hepatoma nuclei was three times greater from liver as compared to hepatoma cytosol; both cytosols showed an apparent saturation of nuclear receptor sites. Although the competitive interaction of the receptor complex with nuclei suggested that they were qualitatively similar, the translocation of additional dexamethasone-receptor from liver cytosol into nuclei presaturated with the receptor complex from hepatoma cytosol suggested that they were different. However, the latter observation, as well as the initial differential nuclear uptake of the dexamethasone-receptor complex from liver and hepatoma cytosols, can be accounted for by a higher concentration of a translocation inhibitor in the hepatoma cytosol. Thus hepatoma cytosol, at a protein concentration of 6 mg/ml and free of activated receptor complex, was four times more inhibitory to nuclear uptake of the activated complex than was a comparable preparation of liver cytosol. A study of the kinetics of nuclear uptake of the partially purified dexamethasone-receptor complex from hepatoma confirmed that, in the absence of cytoplasmic translocation inhibitor, nuclear acceptor sites were not limiting in vitro. Evidence is presented which suggests, but does not prove, that the cytoplasmic translocation inhibitor functions as such in the intact cell.", "contents": "Elevated concentration of a dexamethasone-receptor translocation inhibitor in Novikoff hepatoma cells. Despite the apparent similarity of the dexamethasone-receptor concentration in the rat liver and Novikoff hepatoma cytoplasms, the in vitro translocation of the dexamethasone-receptor complex into liver or hepatoma nuclei was three times greater from liver as compared to hepatoma cytosol; both cytosols showed an apparent saturation of nuclear receptor sites. Although the competitive interaction of the receptor complex with nuclei suggested that they were qualitatively similar, the translocation of additional dexamethasone-receptor from liver cytosol into nuclei presaturated with the receptor complex from hepatoma cytosol suggested that they were different. However, the latter observation, as well as the initial differential nuclear uptake of the dexamethasone-receptor complex from liver and hepatoma cytosols, can be accounted for by a higher concentration of a translocation inhibitor in the hepatoma cytosol. Thus hepatoma cytosol, at a protein concentration of 6 mg/ml and free of activated receptor complex, was four times more inhibitory to nuclear uptake of the activated complex than was a comparable preparation of liver cytosol. A study of the kinetics of nuclear uptake of the partially purified dexamethasone-receptor complex from hepatoma confirmed that, in the absence of cytoplasmic translocation inhibitor, nuclear acceptor sites were not limiting in vitro. Evidence is presented which suggests, but does not prove, that the cytoplasmic translocation inhibitor functions as such in the intact cell."}
{"id": "PMID:192461", "title": "Murine sarcoma virus pseudotypes used as immunogens against viral and chemical oncogenesis.", "content": "The purpose of this study was to develop an animal system of protective immunity against oncornaviruses and to test whether such immunization had an inhibitory effect upon chemical sarcomagenesis. Several murine sarcoma virus (MSV) pseudotypes were used as immunogens and tested against themselves, against other pseudotypes, against leukemogenesis by their helper viruses, and against sarcomagenesis by 3-methylcholanthrene. Five MSV pseudotypes were obtained by rescuing complete MSV from MSV-genome carrier, nonproducer hamster tumor cells, using five different leukemia viruses as helpers. The immunogenic properties of these pseudotypes could be specified on the basis of the following observations. 1) They all induced sarcomas in newborn mice and regressing sarcoma nodules in young adult mice. After regression, most mice remained free of neoplastic disease, but some developed sarcoma or leukemia relapses. 2) They had an individual host range pattern, usually determined by the helper virus, as tested by inoculation of a constant virus dose in BALB/c, C57BL/Ka, and Swiss mice. 3) They were all immunogenic, in the sense that the first virus inoculation prevented sarcoma induction by a second challenge, either viral or cellular. 4) They were cross-reactive in vivo, one pseudotype immunizing against another, in the combinations tested. 5) They were able to immunize against leukemogenesis induced by their helper viruses. This was shown by prevention of leukemic deaths by Rauscher and Friend viruses, by a slight prolongation of survival after challenge with the Precerutti-Law leukemia virus, and by inhibition of splenomegaly by Moloney leukemia virus. In a second stage of the study, we investigated whether immunization with any of the MSV psuedotypes had an inhibitory effect upon sarcomagenesis induced by near-threshold doses of 3-methylcholanthrene. The incidence of these sarcomas was essentially the same in virus-immunized and control mice. It was concluded that immunizing procedures able to prevent sarcomagenesis when the inducer is a virus did not have any consistent preventive effect when the inducer was a chemical.", "contents": "Murine sarcoma virus pseudotypes used as immunogens against viral and chemical oncogenesis. The purpose of this study was to develop an animal system of protective immunity against oncornaviruses and to test whether such immunization had an inhibitory effect upon chemical sarcomagenesis. Several murine sarcoma virus (MSV) pseudotypes were used as immunogens and tested against themselves, against other pseudotypes, against leukemogenesis by their helper viruses, and against sarcomagenesis by 3-methylcholanthrene. Five MSV pseudotypes were obtained by rescuing complete MSV from MSV-genome carrier, nonproducer hamster tumor cells, using five different leukemia viruses as helpers. The immunogenic properties of these pseudotypes could be specified on the basis of the following observations. 1) They all induced sarcomas in newborn mice and regressing sarcoma nodules in young adult mice. After regression, most mice remained free of neoplastic disease, but some developed sarcoma or leukemia relapses. 2) They had an individual host range pattern, usually determined by the helper virus, as tested by inoculation of a constant virus dose in BALB/c, C57BL/Ka, and Swiss mice. 3) They were all immunogenic, in the sense that the first virus inoculation prevented sarcoma induction by a second challenge, either viral or cellular. 4) They were cross-reactive in vivo, one pseudotype immunizing against another, in the combinations tested. 5) They were able to immunize against leukemogenesis induced by their helper viruses. This was shown by prevention of leukemic deaths by Rauscher and Friend viruses, by a slight prolongation of survival after challenge with the Precerutti-Law leukemia virus, and by inhibition of splenomegaly by Moloney leukemia virus. In a second stage of the study, we investigated whether immunization with any of the MSV psuedotypes had an inhibitory effect upon sarcomagenesis induced by near-threshold doses of 3-methylcholanthrene. The incidence of these sarcomas was essentially the same in virus-immunized and control mice. It was concluded that immunizing procedures able to prevent sarcomagenesis when the inducer is a virus did not have any consistent preventive effect when the inducer was a chemical."}
{"id": "PMID:192462", "title": "Repair of DNA in human cells after treatment with activated aflatoxin B1.", "content": "Repair replication was examined in cultured human cells exposed to the hepatocarcinogen aflatoxin B1 using the combined bromodeoxyuridine density label and radioisotopic label method. Semiconservative DNA synthesis was strongly inhibited, and the repair replication mode was stimulated in diploid fibroblasts (W138) and in their SV40 transformants (VA13) only when exposure to aflatoxin B1 was in the presence of an activating system containing rat liver microsomal enzymes. The maximum amount of repair synthesis was about 20% of that obtained after saturating doses of ultraviolet light (UV). The time course of repair synthesis was similar to that seen after UV, and most of the synthesis was in 30- to 50-nucleotide \"short patches.\" A line of SV40-transformed xeroderma pigmentosum cells (Group A) deficient in repair after exposure to UV was similarly deficient in repair replication after aflatoxin treatment. Treatment with aflatoxin resulted in a 25 to 45% inhibition of UV-induced repair replication, suggesting that in addition to producing lesions in DNA, which are substrates for the excision repair system, the toxin also inhibits excision repair. CsC1 gradients of DNA treated in vitro with activated aflatoxin demonstrated binding of the drug to DNA. Alkaline sucrose gradient sedimentation gave no indication that single-strand breaks or alkali labile bonds were introduced into DNA by treatment of cells with activated aflatoxin.", "contents": "Repair of DNA in human cells after treatment with activated aflatoxin B1. Repair replication was examined in cultured human cells exposed to the hepatocarcinogen aflatoxin B1 using the combined bromodeoxyuridine density label and radioisotopic label method. Semiconservative DNA synthesis was strongly inhibited, and the repair replication mode was stimulated in diploid fibroblasts (W138) and in their SV40 transformants (VA13) only when exposure to aflatoxin B1 was in the presence of an activating system containing rat liver microsomal enzymes. The maximum amount of repair synthesis was about 20% of that obtained after saturating doses of ultraviolet light (UV). The time course of repair synthesis was similar to that seen after UV, and most of the synthesis was in 30- to 50-nucleotide \"short patches.\" A line of SV40-transformed xeroderma pigmentosum cells (Group A) deficient in repair after exposure to UV was similarly deficient in repair replication after aflatoxin treatment. Treatment with aflatoxin resulted in a 25 to 45% inhibition of UV-induced repair replication, suggesting that in addition to producing lesions in DNA, which are substrates for the excision repair system, the toxin also inhibits excision repair. CsC1 gradients of DNA treated in vitro with activated aflatoxin demonstrated binding of the drug to DNA. Alkaline sucrose gradient sedimentation gave no indication that single-strand breaks or alkali labile bonds were introduced into DNA by treatment of cells with activated aflatoxin."}
{"id": "PMID:192463", "title": "Leukemogenesis in vitro induced by thymus epithelial reticulum cells transmitting murine leukemia viruses.", "content": "The role of the thymus in induction of leukemia was studied in vitro. Curltivation of normal thymus cells on thymus epithelial reticulum cell monolayers that had been grown from radiation leukemia virus-induced leukemic thymuses rendered the thymocytes leukemic. C57BL/6 thymocytes were cultivated for 3 days on leukemic thymus reticulum monolayers, and 106 thymocytes were injected i.p. into young adult C57BL/6 mice. After 3 to 4 weeks all mice died of disseminated lymphatic leukemia. Mice given thymocytes that had been cultivated on thymus epithelial reticulum monolayers from normal mice did not develop lymphomas. The leukemic thymus epithelial reticulum cells were shown to produce thymotropic as well as ecotropic and xenotropic radiation leukemia virus. (Thymotropic virus has affinity for thymus lymphocytes but noes not infect fibroblasts.) The cells were brightly positive for murine leukemia virus group-specific antigen in immunofluorescence tests. Leukemic thymus epithelial reticulum cells produced ample infectious exotropic virus in the culture supernatant, although the cells were negative in the XC syncytia test. Upon infection of mouse fibroblasts with ecotropic virus produced by the leukemic reticulum cells, XC syncytia were readily obtained. Thymocytes that were cultivated on leukemic thymus reticulum cells became positive for murine leukemia virus group-specific antigen and produced syncytia in the XC test. Thus, in vitro lymphomagenesis of the thymocytes that were cultured on leukemic thymus reticulum cells was associated with their infection with thymotropic and ecotropic radiation leukemia virus.", "contents": "Leukemogenesis in vitro induced by thymus epithelial reticulum cells transmitting murine leukemia viruses. The role of the thymus in induction of leukemia was studied in vitro. Curltivation of normal thymus cells on thymus epithelial reticulum cell monolayers that had been grown from radiation leukemia virus-induced leukemic thymuses rendered the thymocytes leukemic. C57BL/6 thymocytes were cultivated for 3 days on leukemic thymus reticulum monolayers, and 106 thymocytes were injected i.p. into young adult C57BL/6 mice. After 3 to 4 weeks all mice died of disseminated lymphatic leukemia. Mice given thymocytes that had been cultivated on thymus epithelial reticulum monolayers from normal mice did not develop lymphomas. The leukemic thymus epithelial reticulum cells were shown to produce thymotropic as well as ecotropic and xenotropic radiation leukemia virus. (Thymotropic virus has affinity for thymus lymphocytes but noes not infect fibroblasts.) The cells were brightly positive for murine leukemia virus group-specific antigen in immunofluorescence tests. Leukemic thymus epithelial reticulum cells produced ample infectious exotropic virus in the culture supernatant, although the cells were negative in the XC syncytia test. Upon infection of mouse fibroblasts with ecotropic virus produced by the leukemic reticulum cells, XC syncytia were readily obtained. Thymocytes that were cultivated on leukemic thymus reticulum cells became positive for murine leukemia virus group-specific antigen and produced syncytia in the XC test. Thus, in vitro lymphomagenesis of the thymocytes that were cultured on leukemic thymus reticulum cells was associated with their infection with thymotropic and ecotropic radiation leukemia virus."}
{"id": "PMID:192465", "title": "Comparison of the growth properties in vitro and transplantability of continuous mouse mammary tumor cell lines and clonal derivatives.", "content": "Five continuous mouse mammary tumor cell lines and 12 clonal derivatives have been established from tumors arising in BALB/c or C3H mice either spontaneously or in response to viral (mammary tumor virus), hormonal (17 beta-estradiol), or chemical [7,12-dimethylbenz(alpha)anthracene] stimuli in vivo. The cell lines were examined for the following in vitro growth parameters:plating efficiency, saturation density, population-doubling times, colony formation on plastic surfaces, and anchorage-independent growth in methylcellulose. The majority of the mammary tumor cell lines were transplantable in syngeneic, immunocompetent mice and gave rise to tumors composed of epithelial cells. There was no growth parameter in vitro which invariably correlated with tumorigenicity in vivo. Most of the mammary tumor cell lines appeared to produce C-type virus. Only one, a C3H derivative, appeared to respond to stimulation by glucocorticoids with the enhanced production of B-type virus. Analysis of the growth properties exhibited in culture by transformed mammary epithelial cells revealed marked differences from those previously reported for transformed fibroblasts.", "contents": "Comparison of the growth properties in vitro and transplantability of continuous mouse mammary tumor cell lines and clonal derivatives. Five continuous mouse mammary tumor cell lines and 12 clonal derivatives have been established from tumors arising in BALB/c or C3H mice either spontaneously or in response to viral (mammary tumor virus), hormonal (17 beta-estradiol), or chemical [7,12-dimethylbenz(alpha)anthracene] stimuli in vivo. The cell lines were examined for the following in vitro growth parameters:plating efficiency, saturation density, population-doubling times, colony formation on plastic surfaces, and anchorage-independent growth in methylcellulose. The majority of the mammary tumor cell lines were transplantable in syngeneic, immunocompetent mice and gave rise to tumors composed of epithelial cells. There was no growth parameter in vitro which invariably correlated with tumorigenicity in vivo. Most of the mammary tumor cell lines appeared to produce C-type virus. Only one, a C3H derivative, appeared to respond to stimulation by glucocorticoids with the enhanced production of B-type virus. Analysis of the growth properties exhibited in culture by transformed mammary epithelial cells revealed marked differences from those previously reported for transformed fibroblasts."}
{"id": "PMID:192466", "title": "Factors affecting deoxycytidylate deaminase activity in some transplantable rat hepatomas.", "content": "Dunning hepatoma has a low activity of deoxycytidylate deaminase, comparable to that of normal adult rat liver. This activity seems inconsistent with the rapid proliferation rate of the tumor. Factors which might affect the activity of deoxycytidylate deaminase in the Dunning hepatoma have been examined in it and compared to the Novikoff hepatoma which has high activity of this enzyme. The low activity in Dunning hepatoma does not appear to be the result of any inhibition or, possibly, proteolytic enzyme as judged by mixing experiments, nor does it appear to be due to in vivo differences in nucleotide concentrations especially deoxycytidine 5'-monophosphate, deoxycytidine 5'-triphosphate, or deoxyguanosine 5'-monophosphate which might either help stabilize the enzyme, allosterically increase its activity, or inhibit it. The Dunning hepatoma does not convert cytosine deoxyriboside to uridine deoxyriboside at a significant rate, and the formation of uridine deoxyriboside from deoxyuridine monophosphate is 1% or less during a 30-min incubation of high-speed supernatant fraction from the tumor in either the presence or absence of fluoride. It is concluded that the Dunning hepatoma probably has intrinsically low deoxycytidylate deaminase activity.", "contents": "Factors affecting deoxycytidylate deaminase activity in some transplantable rat hepatomas. Dunning hepatoma has a low activity of deoxycytidylate deaminase, comparable to that of normal adult rat liver. This activity seems inconsistent with the rapid proliferation rate of the tumor. Factors which might affect the activity of deoxycytidylate deaminase in the Dunning hepatoma have been examined in it and compared to the Novikoff hepatoma which has high activity of this enzyme. The low activity in Dunning hepatoma does not appear to be the result of any inhibition or, possibly, proteolytic enzyme as judged by mixing experiments, nor does it appear to be due to in vivo differences in nucleotide concentrations especially deoxycytidine 5'-monophosphate, deoxycytidine 5'-triphosphate, or deoxyguanosine 5'-monophosphate which might either help stabilize the enzyme, allosterically increase its activity, or inhibit it. The Dunning hepatoma does not convert cytosine deoxyriboside to uridine deoxyriboside at a significant rate, and the formation of uridine deoxyriboside from deoxyuridine monophosphate is 1% or less during a 30-min incubation of high-speed supernatant fraction from the tumor in either the presence or absence of fluoride. It is concluded that the Dunning hepatoma probably has intrinsically low deoxycytidylate deaminase activity."}
{"id": "PMID:192467", "title": "The reduction of uridine 5'-diphosphate and uridine 5'-triphosphate in some transplantable rat hepatomas.", "content": "The reduction of uridine 5'-diphosphate (UDP) and uridine 5'-triphosphate (UTP) has been studied in normal adult rat liver, the Dunning hepatoma, and Morris 5123D and 7793 hepatomas. A new paper chromatographic method that separates and quantitates all the major products of the reduction and hydrolysis or other reactions of the substrate has been devised. All of the above tissues were able to reduce UDP and UTP at relatively slow rates ranging from 0.25 nmole of deoxycompound formed (deoxyuridine 5'-triphosphate) per mg protein per hr for liver to 3.5 nmoles deoxyuridine 5'-triphosphate for the Morris 7793 hepatoma when UTP was the substrate. In general, UTP was a better substrate than UDP. The method may also be used to measure cytidine 5'-diphosphate (CDP) reduction, and under the same conditions, the reduction of CDP proceeded at about 6 times the rate of UTP reduction in the Dunning hepatoma. Like CDP reduction, the reduction of UTP was strongly modulated by ATP. Reduction of UTP was insignificant with no ATP or 1.5 micronmoles ATP added to the reaction mixture and was maximal with 0.25 micronmole. The reduction of UTP was inhibited by deoxyuridine 5'-monophosphate, deoxythymidine 5'-triphosphate, deoxycytidine 5'-triphosphate, and deoxyribose 1'-phosphate. The effects of deoxyadenosine 5'-triphosphate varied, depending on its concentration in the reaction medium and whether UDP or UTP was a substrate. However, hydroxyurea did not inhibit reduction of UDP or UTP at concentrations that strongly inhibited CPD reduction. All of the tissues were able to hydrolyze [alpha-32P]deoxyuridine 5'-triphosphate readily to the diphosphate and monophosphate. It is suggested that the enzyme that reduces UTP or UDP may be different in these tissues from the enzyme that reduces CDP.", "contents": "The reduction of uridine 5'-diphosphate and uridine 5'-triphosphate in some transplantable rat hepatomas. The reduction of uridine 5'-diphosphate (UDP) and uridine 5'-triphosphate (UTP) has been studied in normal adult rat liver, the Dunning hepatoma, and Morris 5123D and 7793 hepatomas. A new paper chromatographic method that separates and quantitates all the major products of the reduction and hydrolysis or other reactions of the substrate has been devised. All of the above tissues were able to reduce UDP and UTP at relatively slow rates ranging from 0.25 nmole of deoxycompound formed (deoxyuridine 5'-triphosphate) per mg protein per hr for liver to 3.5 nmoles deoxyuridine 5'-triphosphate for the Morris 7793 hepatoma when UTP was the substrate. In general, UTP was a better substrate than UDP. The method may also be used to measure cytidine 5'-diphosphate (CDP) reduction, and under the same conditions, the reduction of CDP proceeded at about 6 times the rate of UTP reduction in the Dunning hepatoma. Like CDP reduction, the reduction of UTP was strongly modulated by ATP. Reduction of UTP was insignificant with no ATP or 1.5 micronmoles ATP added to the reaction mixture and was maximal with 0.25 micronmole. The reduction of UTP was inhibited by deoxyuridine 5'-monophosphate, deoxythymidine 5'-triphosphate, deoxycytidine 5'-triphosphate, and deoxyribose 1'-phosphate. The effects of deoxyadenosine 5'-triphosphate varied, depending on its concentration in the reaction medium and whether UDP or UTP was a substrate. However, hydroxyurea did not inhibit reduction of UDP or UTP at concentrations that strongly inhibited CPD reduction. All of the tissues were able to hydrolyze [alpha-32P]deoxyuridine 5'-triphosphate readily to the diphosphate and monophosphate. It is suggested that the enzyme that reduces UTP or UDP may be different in these tissues from the enzyme that reduces CDP."}
{"id": "PMID:192471", "title": "Growth stimulation of sparse, serum deprived and of confluent, contact inhibited mammalian fibroblasts by a preparation of 3':5'-cyclic AMP phosphodiesterase.", "content": "Resting mammalian fibroblasts, either sparse and maintained in a serum-free medium, or confluent and contact inhibited, are stimulated to divide by treatment with a preparation of 3':5'-cyclic AMP phosphodiesterase. This enzyme preparation contained a low level of trypsin-like and alpha-chymotrypsin-like activity, but its effect on cell growth could not be mimicked by pure, crystallized trypsin and alpha-chymotrypsin at concentration equivalent to their contamination in the above preparation. Preincubation of the 3':5'-cyclic AMP phosphodiesterase preparation with the protease inhibitor, phenyl methane sulfonyl fulride, did not affect, either, its stimulation of DNA synthesis in fibroblasts, or its enzymatic hydrolysis of cyclic AMP.", "contents": "Growth stimulation of sparse, serum deprived and of confluent, contact inhibited mammalian fibroblasts by a preparation of 3':5'-cyclic AMP phosphodiesterase. Resting mammalian fibroblasts, either sparse and maintained in a serum-free medium, or confluent and contact inhibited, are stimulated to divide by treatment with a preparation of 3':5'-cyclic AMP phosphodiesterase. This enzyme preparation contained a low level of trypsin-like and alpha-chymotrypsin-like activity, but its effect on cell growth could not be mimicked by pure, crystallized trypsin and alpha-chymotrypsin at concentration equivalent to their contamination in the above preparation. Preincubation of the 3':5'-cyclic AMP phosphodiesterase preparation with the protease inhibitor, phenyl methane sulfonyl fulride, did not affect, either, its stimulation of DNA synthesis in fibroblasts, or its enzymatic hydrolysis of cyclic AMP."}
{"id": "PMID:192472", "title": "Lateral enzyme topology in the rough endoplasmic reticulum of rat liver.", "content": "Rough microsomes were subfractionated on the basis of different properties in order to investigate the nature and extent of the enzyme heterogeneity of these vesicles. A discontinuous gradient, containing monovalent cations allowed the separation of a ribosome-poor membrane fraction which was enriched in electron transport enzymes and relatively poor in phosphatases. Zonal centrifugation on a stabilizing gradient separated 3 fractions characterized by enrichment of electron transport enzymes, glucose-6-phosphatase and adenosinetriphosphatase, respectively. An essentially similar pattern was seen when ribosomes were removed with EDTA and the denuded vesicles subfractionated on a sucrose gradient. Rough microsomes from phenobarbital-treated rats exhibited the same pattern both qualitatively and quantitatively. It appears that electron transport enzymes and two types of phosphatases are heterogeneously distributed among rough microsomal vesicles.", "contents": "Lateral enzyme topology in the rough endoplasmic reticulum of rat liver. Rough microsomes were subfractionated on the basis of different properties in order to investigate the nature and extent of the enzyme heterogeneity of these vesicles. A discontinuous gradient, containing monovalent cations allowed the separation of a ribosome-poor membrane fraction which was enriched in electron transport enzymes and relatively poor in phosphatases. Zonal centrifugation on a stabilizing gradient separated 3 fractions characterized by enrichment of electron transport enzymes, glucose-6-phosphatase and adenosinetriphosphatase, respectively. An essentially similar pattern was seen when ribosomes were removed with EDTA and the denuded vesicles subfractionated on a sucrose gradient. Rough microsomes from phenobarbital-treated rats exhibited the same pattern both qualitatively and quantitatively. It appears that electron transport enzymes and two types of phosphatases are heterogeneously distributed among rough microsomal vesicles."}
{"id": "PMID:192473", "title": "Morphological equivalent of the bifunctional role of somatostatin.", "content": "Using the immunoenzyme bridge-technique at the light and electron microscopic levels, somatostatin can be demonstrated in the perikarya of the anterior periventricular nucleus, in the median eminence and in the parvocellular hypothalamic nuclei of the rat. In the latter regions the perikarya are negative, whereas a positive reaction for somatostatin is found in a delicate network of fibers and middle-sized granules of very small axons. In light of these results, the double function of somatostatin-as release inhibiting hormone and as transmitter-is discussed. The positive staining reaction in the organum vasculosum laminae terminalis of male and female rats as well as in the subfornical organ, the nucleus dorsalis thalami and the nucleus medialis habenulae in female controls and pregnant rats is not due to somatostatin-containing structures, but partly to substance P and partlly to a substance which could not be defined.", "contents": "Morphological equivalent of the bifunctional role of somatostatin. Using the immunoenzyme bridge-technique at the light and electron microscopic levels, somatostatin can be demonstrated in the perikarya of the anterior periventricular nucleus, in the median eminence and in the parvocellular hypothalamic nuclei of the rat. In the latter regions the perikarya are negative, whereas a positive reaction for somatostatin is found in a delicate network of fibers and middle-sized granules of very small axons. In light of these results, the double function of somatostatin-as release inhibiting hormone and as transmitter-is discussed. The positive staining reaction in the organum vasculosum laminae terminalis of male and female rats as well as in the subfornical organ, the nucleus dorsalis thalami and the nucleus medialis habenulae in female controls and pregnant rats is not due to somatostatin-containing structures, but partly to substance P and partlly to a substance which could not be defined."}
{"id": "PMID:192474", "title": "Disruption of multicellular organization in the cellular slime molds by cyclic AMP.", "content": "Addition of cyclic AMP causes disorder in the multicellular stage of a number of species of cellular slime molds. In those which produce fruits with cellular stalks, the addition of cyclic AMP stimulates prestalk cells to differentiate into mature stalk cells. Prespore cells do not differentiate into spores under the influence of cyclic AMP, most degenerate and seem to die. I hypothesize that the normal course of differentiation from vegetative cells is one leading to spores, but that cyclic AMP can divert this course to one leading to the stalk cell. Dibutyryl cyclic AMP, cyclic GMP and cyclic AMP disrupt slugs of Polysphondylium pallidum, while species of Dictyostelium are disrupted by only cyclic AMP. The multicellular stage of P. violaceum is unaffected by high concentrations of exogenous cyclic nucleotides. Cell organization of Acytostelium ellipticum, a species with an acellular stalk, was disrupted by cyclic AMP, but no stalk cells were formed; only spores.", "contents": "Disruption of multicellular organization in the cellular slime molds by cyclic AMP. Addition of cyclic AMP causes disorder in the multicellular stage of a number of species of cellular slime molds. In those which produce fruits with cellular stalks, the addition of cyclic AMP stimulates prestalk cells to differentiate into mature stalk cells. Prespore cells do not differentiate into spores under the influence of cyclic AMP, most degenerate and seem to die. I hypothesize that the normal course of differentiation from vegetative cells is one leading to spores, but that cyclic AMP can divert this course to one leading to the stalk cell. Dibutyryl cyclic AMP, cyclic GMP and cyclic AMP disrupt slugs of Polysphondylium pallidum, while species of Dictyostelium are disrupted by only cyclic AMP. The multicellular stage of P. violaceum is unaffected by high concentrations of exogenous cyclic nucleotides. Cell organization of Acytostelium ellipticum, a species with an acellular stalk, was disrupted by cyclic AMP, but no stalk cells were formed; only spores."}
{"id": "PMID:192475", "title": "The effect of adenosine-3':5'-cyclic monophosphate on the mitotic rate in regenerating Dugesia dorotocephala.", "content": "Regenerating posterior sections of the flatworm, Dugesia dorotocephala, were treated with varying concentrations of 5'-adenosine monophosphate (AMP), cyclic AMP (cAMP) and dibutyryl cyclic AMP (Bt2cAMP) for 24 h. M/2000 colchicine was added to the medium during the final 4 h of treatment to collect mitotic figures. The mitotic rate was significantly increased at 0.5, 0.1 and 0.01 mM concentrations of Bt2-cAMP. While Bt2cAMP and cAMP produced comparable results at 0.01 mM, only the Bt2-cAMP-treated organisms exhibited a significantly higher mitotic rate at the 0.1 mM concentration. Theophylline and sodium butyrate did not evoke any stimulatory effect on mitotic rate.", "contents": "The effect of adenosine-3':5'-cyclic monophosphate on the mitotic rate in regenerating Dugesia dorotocephala. Regenerating posterior sections of the flatworm, Dugesia dorotocephala, were treated with varying concentrations of 5'-adenosine monophosphate (AMP), cyclic AMP (cAMP) and dibutyryl cyclic AMP (Bt2cAMP) for 24 h. M/2000 colchicine was added to the medium during the final 4 h of treatment to collect mitotic figures. The mitotic rate was significantly increased at 0.5, 0.1 and 0.01 mM concentrations of Bt2-cAMP. While Bt2cAMP and cAMP produced comparable results at 0.01 mM, only the Bt2-cAMP-treated organisms exhibited a significantly higher mitotic rate at the 0.1 mM concentration. Theophylline and sodium butyrate did not evoke any stimulatory effect on mitotic rate."}
{"id": "PMID:192479", "title": "Spin label study of detergents in the region of critical micelle concentration.", "content": "A series of spin probes was employed to examine the behavior of the detergent sodium dodecyl sulfate (SDS) at concentrations above and below the critical micelle concentration (cmc). The existence of detergent aggregates below the cmc was evidenced by the appearance of composite electron spin resonance (ESR) spectra for probes that have measurable solubility in water. The spectra were indicative of two probe populations: one in an aqueous environment and another in detergent aggregates. The ESR spectra of probes which are highly insoluble in water exhibited line broadening due to intermolecular spin exchange interactions, indicating that the probes were concentrated in detergent aggregates present below the experimental cmc. The results are discussed in terms of their significance for the study of the mechanisms of micelle formation and for the detection of detergent aggregates at very low concentrations.", "contents": "Spin label study of detergents in the region of critical micelle concentration. A series of spin probes was employed to examine the behavior of the detergent sodium dodecyl sulfate (SDS) at concentrations above and below the critical micelle concentration (cmc). The existence of detergent aggregates below the cmc was evidenced by the appearance of composite electron spin resonance (ESR) spectra for probes that have measurable solubility in water. The spectra were indicative of two probe populations: one in an aqueous environment and another in detergent aggregates. The ESR spectra of probes which are highly insoluble in water exhibited line broadening due to intermolecular spin exchange interactions, indicating that the probes were concentrated in detergent aggregates present below the experimental cmc. The results are discussed in terms of their significance for the study of the mechanisms of micelle formation and for the detection of detergent aggregates at very low concentrations."}
{"id": "PMID:192480", "title": "Wilms' tumor: evaluation of histological features.", "content": "In order to evaluate the factors relating to prognosis, a clinico-pathological study was made in 27 patients with Wilms' tumor. Among these 27 cases, 10 survived more than two years after nephrectomy, 16 died within four days up to two years, and one patient could not be followed up. The younger age group and earlier stage of the disease showed more favorable prognosis. The tumor size, location, and number of tumor nodules had no effect on prognosis. Both the lymphatic and capsular invasions were common in the fatal cases. No vascular invasion was seen in any patient that had preoperative radiotherapy. Among the 10 survivors, six patients had received preoperative irradiation, whose tumors revealed a mesoblastic pattern. Polycystic structures were found in two surviving cases. One survivor's tumor contained prominent squamous epithelium. Another case showed predominance of undifferentiated spindle cells. The undifferentiated mesenchymal type with sarcomatous pattern would not always represent unfavorable prognosis. The tumor with mesoblastic pattern after radiotherapy and those with polycystic structure showed low-grade malignancy and maturation of stromal cells and tubules, respectively.", "contents": "Wilms' tumor: evaluation of histological features. In order to evaluate the factors relating to prognosis, a clinico-pathological study was made in 27 patients with Wilms' tumor. Among these 27 cases, 10 survived more than two years after nephrectomy, 16 died within four days up to two years, and one patient could not be followed up. The younger age group and earlier stage of the disease showed more favorable prognosis. The tumor size, location, and number of tumor nodules had no effect on prognosis. Both the lymphatic and capsular invasions were common in the fatal cases. No vascular invasion was seen in any patient that had preoperative radiotherapy. Among the 10 survivors, six patients had received preoperative irradiation, whose tumors revealed a mesoblastic pattern. Polycystic structures were found in two surviving cases. One survivor's tumor contained prominent squamous epithelium. Another case showed predominance of undifferentiated spindle cells. The undifferentiated mesenchymal type with sarcomatous pattern would not always represent unfavorable prognosis. The tumor with mesoblastic pattern after radiotherapy and those with polycystic structure showed low-grade malignancy and maturation of stromal cells and tubules, respectively."}
{"id": "PMID:192481", "title": "[Different sensitivities to ultraviolet rays of various functions of the polyoma virus. Stimulation of the synthesis of cellular DNA].", "content": "Peritoneal Mouse macrophage were used to study the stimulation of cell DNA synthesis by polyoma virus. Using ultraviolet-irradiated polyoma virus, it was possible to show a difference between the inactivations of infectivity and of induction of DNA synthesis. By statistically analysis of these two phenomena it was found that 39% of the viral genome is necessary for the induction of cell DNA synthesis.", "contents": "[Different sensitivities to ultraviolet rays of various functions of the polyoma virus. Stimulation of the synthesis of cellular DNA]. Peritoneal Mouse macrophage were used to study the stimulation of cell DNA synthesis by polyoma virus. Using ultraviolet-irradiated polyoma virus, it was possible to show a difference between the inactivations of infectivity and of induction of DNA synthesis. By statistically analysis of these two phenomena it was found that 39% of the viral genome is necessary for the induction of cell DNA synthesis."}
{"id": "PMID:192482", "title": "[Age-and sex-related development of ACTH in the pars distalis and neurointermedia of rat pituitary].", "content": "The content of ACTH of the pars distalis and neurointermedia of the pituitary of adult Rats is higher in the male than in the female. This differenciation of content, according to sex, appears at puberty at the site of pars distalis; it only appears around the 60th day of life at the site of the pars intermedia. The androgens seem to be responsible for the higher percentages observed in the males.", "contents": "[Age-and sex-related development of ACTH in the pars distalis and neurointermedia of rat pituitary]. The content of ACTH of the pars distalis and neurointermedia of the pituitary of adult Rats is higher in the male than in the female. This differenciation of content, according to sex, appears at puberty at the site of pars distalis; it only appears around the 60th day of life at the site of the pars intermedia. The androgens seem to be responsible for the higher percentages observed in the males."}
{"id": "PMID:192483", "title": "[Histochemical localization of lactate dehydrogenase in the trout embryo (Salmo irideus, Gibb) during early organogenesis of the cord and the neural tube].", "content": "The histochemical study of the LDH in the Trout embryo during the early organogenesis shows a specific localization in notochord cells, in mesodermic cells of the terminal knob and in some prosencephalic neuroblasts. The role of the LDH in the metabolism of NAD as well as in the energetic metabolism of embryonic cells is discussed.", "contents": "[Histochemical localization of lactate dehydrogenase in the trout embryo (Salmo irideus, Gibb) during early organogenesis of the cord and the neural tube]. The histochemical study of the LDH in the Trout embryo during the early organogenesis shows a specific localization in notochord cells, in mesodermic cells of the terminal knob and in some prosencephalic neuroblasts. The role of the LDH in the metabolism of NAD as well as in the energetic metabolism of embryonic cells is discussed."}
{"id": "PMID:192484", "title": "[Immunofluorescence identification of cells with corticotropic and alpha-melanotropic activity in the hypophysis of the grass snake Natrix natrix L].", "content": "The use of anti ACTH (17-39) and alpha-MSH allowed us to detect by immunofluorescence in the Pituitary gland of Grass Snake the site of elaboration of ACTH and alpha-MSH. Corticotropic cells are located in the rostral part of the Pars Distalis and in the Pars intermedia. Melanotropic cells occupy the whole part of the Pars intermedia.", "contents": "[Immunofluorescence identification of cells with corticotropic and alpha-melanotropic activity in the hypophysis of the grass snake Natrix natrix L]. The use of anti ACTH (17-39) and alpha-MSH allowed us to detect by immunofluorescence in the Pituitary gland of Grass Snake the site of elaboration of ACTH and alpha-MSH. Corticotropic cells are located in the rostral part of the Pars Distalis and in the Pars intermedia. Melanotropic cells occupy the whole part of the Pars intermedia."}
{"id": "PMID:192485", "title": "[Potentiating effect of cycloheximide on viral interference].", "content": "The degradation of the antiviral state can be delayed in vitro by antimetabolites, when added between 5-7 hours after interferon. We explore in this chronological order whether antiviral resistance induced by Newcastle disease virus (N.D.V.) in vivo could be modified by an antimetabolite. Cycloheximide was selected for this study because of its reversible biological effect and lack of toxicity in our experimental conditions. The model system employed was Syrian Hamsters, using N.D.V. as an interferon inducer and encephalomyocarditis virus (E.M.C.) as a challenge virus. A constant and significant increase in survival of animals treated with N.D.V.+cycloheximide is probably related to a delay in the degradation of the antiviral state and not to interferon superinduction.", "contents": "[Potentiating effect of cycloheximide on viral interference]. The degradation of the antiviral state can be delayed in vitro by antimetabolites, when added between 5-7 hours after interferon. We explore in this chronological order whether antiviral resistance induced by Newcastle disease virus (N.D.V.) in vivo could be modified by an antimetabolite. Cycloheximide was selected for this study because of its reversible biological effect and lack of toxicity in our experimental conditions. The model system employed was Syrian Hamsters, using N.D.V. as an interferon inducer and encephalomyocarditis virus (E.M.C.) as a challenge virus. A constant and significant increase in survival of animals treated with N.D.V.+cycloheximide is probably related to a delay in the degradation of the antiviral state and not to interferon superinduction."}
{"id": "PMID:192486", "title": "Contractile and biochemical responses of cardiac and skeletal muscle to isoproterenol covalently linked to glass beads.", "content": "The effects of (-)-isoproterenol covalently linked to glass beads on inotropic state, cyclic AMP concentration, and phosphorylase b to a conversion was studied in cat and guinea pig papillary muscles. Biochemical responses also were measured in mouse diaphragm sections. In cat papillary muscles under normal conditions and in guinea pig muscles partly depolarized with 22 mM K+ an increased inotropic state and phosphorylase activation could be dissociated from the formation of cyclic AMP. This contrasts with close correlation reported between isometric tension and cyclic AMP concentration in guinea pig papillary muscles exposed to varying concentrations of isoproterenol dissolved in the bath medium. The cyclic nucleotide did increase in guinea pig papillary muscles exposed to a freshly prepared batch of isoproterenol beads and in the mouse diaphragms. The type and age of the bead preparation had marked effects on all responses that were measured and on the rate of leakage of biologically active products from the beads. Nevertheless, experimental conditions could be obtained under which the initiation of the contractile and biochemical responses was probably limited to intense stimulation of receptors at or near the points of contact between beads and muscle and not due to gross leakage into the bath. The results indicate that cyclic AMP is probably involved in the initiation but not the propagation of the inotropic response of papillary muscles exposed to isoproterenol glass beads.", "contents": "Contractile and biochemical responses of cardiac and skeletal muscle to isoproterenol covalently linked to glass beads. The effects of (-)-isoproterenol covalently linked to glass beads on inotropic state, cyclic AMP concentration, and phosphorylase b to a conversion was studied in cat and guinea pig papillary muscles. Biochemical responses also were measured in mouse diaphragm sections. In cat papillary muscles under normal conditions and in guinea pig muscles partly depolarized with 22 mM K+ an increased inotropic state and phosphorylase activation could be dissociated from the formation of cyclic AMP. This contrasts with close correlation reported between isometric tension and cyclic AMP concentration in guinea pig papillary muscles exposed to varying concentrations of isoproterenol dissolved in the bath medium. The cyclic nucleotide did increase in guinea pig papillary muscles exposed to a freshly prepared batch of isoproterenol beads and in the mouse diaphragms. The type and age of the bead preparation had marked effects on all responses that were measured and on the rate of leakage of biologically active products from the beads. Nevertheless, experimental conditions could be obtained under which the initiation of the contractile and biochemical responses was probably limited to intense stimulation of receptors at or near the points of contact between beads and muscle and not due to gross leakage into the bath. The results indicate that cyclic AMP is probably involved in the initiation but not the propagation of the inotropic response of papillary muscles exposed to isoproterenol glass beads."}
{"id": "PMID:192487", "title": "Defective calcium transport by cardiac sarcoplasmic reticulum in spontaneously hypertensive rats.", "content": "Ca2+ uptake and binding and Ca2+-ATPase activity of cardiac sarcoplasmic reticulum (SR) from spontaneously hypertensive rats (SHR) were compared to that obtained from normotensive Wistar-Kyoto (WKY) rats. Ca2+ uptake (172 +/- 3.7 nmol/mg of protein per min in WKY vs. 112 +/- 2.6 in the SHR, P less than 0.001) and binding (154 +/- 3.0 nmol/mg per min in WKY vs. 101 +/- 1.8 in the SHR, P less than 0.01) were decreased in the SHR. Ca2+-ATPase activity, however, was significantly higher in the SHR (118 +/- 3.1 nmol of P per mg of protein per min vs. 86 +/- 1.1 in the WKY, P less than 0.001), suggesting \"uncoupling\" of the ATPase to calcium transport. Cyclic AMP-dependent phosphorylation of SR was significantly decreased in SHR (0.71 +/- 0.05 vs 0.32 +/- 0.07 nmol of P/mg of protein per 10 min, P less than 0.001) and there was an excellent correlation between cyclic AMP-induced phosphorylation of SR and Ca2+ uptake (r = 0.81). Differences in both cyclic AMP-dependent phosphorylation and Ca2+ uptake between the two groups were evident at 10 weeks and increased progressively to 22 weeks of age. Differences in endogenous cyclic AMP-dependent protein kinase activity may partly explain the decreased Ca2+ transport in SHR.", "contents": "Defective calcium transport by cardiac sarcoplasmic reticulum in spontaneously hypertensive rats. Ca2+ uptake and binding and Ca2+-ATPase activity of cardiac sarcoplasmic reticulum (SR) from spontaneously hypertensive rats (SHR) were compared to that obtained from normotensive Wistar-Kyoto (WKY) rats. Ca2+ uptake (172 +/- 3.7 nmol/mg of protein per min in WKY vs. 112 +/- 2.6 in the SHR, P less than 0.001) and binding (154 +/- 3.0 nmol/mg per min in WKY vs. 101 +/- 1.8 in the SHR, P less than 0.01) were decreased in the SHR. Ca2+-ATPase activity, however, was significantly higher in the SHR (118 +/- 3.1 nmol of P per mg of protein per min vs. 86 +/- 1.1 in the WKY, P less than 0.001), suggesting \"uncoupling\" of the ATPase to calcium transport. Cyclic AMP-dependent phosphorylation of SR was significantly decreased in SHR (0.71 +/- 0.05 vs 0.32 +/- 0.07 nmol of P/mg of protein per 10 min, P less than 0.001) and there was an excellent correlation between cyclic AMP-induced phosphorylation of SR and Ca2+ uptake (r = 0.81). Differences in both cyclic AMP-dependent phosphorylation and Ca2+ uptake between the two groups were evident at 10 weeks and increased progressively to 22 weeks of age. Differences in endogenous cyclic AMP-dependent protein kinase activity may partly explain the decreased Ca2+ transport in SHR."}
{"id": "PMID:192488", "title": "Cholesterol determination in high-density lipoproteins separated by three different methods.", "content": "We describe a simplified method for measuring high-density lipoprotein cholesterol in serum after very-low- and low-density lipoproteins have been precipitated from the specimen with sodium phosphotungstate and Mg2+. Values so obtained correlate well with values obtained with the heparin-Mn2+ precipitation technique (r = 0.95, CV less than 5% in 66% of the subjects studied and between 5 and 10% in the remaining ones) or by ultracentrifugal separation (r = 0.82, CV less than 5% in 80% of the subjects studied and between 5 and 10% in the remaining ones). Our precipitation technique is more appropriate for routine clinical laboratory use.", "contents": "Cholesterol determination in high-density lipoproteins separated by three different methods. We describe a simplified method for measuring high-density lipoprotein cholesterol in serum after very-low- and low-density lipoproteins have been precipitated from the specimen with sodium phosphotungstate and Mg2+. Values so obtained correlate well with values obtained with the heparin-Mn2+ precipitation technique (r = 0.95, CV less than 5% in 66% of the subjects studied and between 5 and 10% in the remaining ones) or by ultracentrifugal separation (r = 0.82, CV less than 5% in 80% of the subjects studied and between 5 and 10% in the remaining ones). Our precipitation technique is more appropriate for routine clinical laboratory use."}
{"id": "PMID:192490", "title": "The beta-lipoprotein doublet in type 3 hyperlipoproteinemia.", "content": "We used a previously reported agarose-gel electrophoresis system to study the lipoprotein patterns in patients with type 3 hyperlipoproteinemia. All samples from 20 subjects tested revealed the presence of two bands with beta-lipoprotein mobility, irrespective of quantitative changes in plasma lipids induced by diet or by the administration of drugs. If these observations are confirmed, the method will permit the diagnosis of type 3 hyperlipoproteinemia without resort to preparative ultracentrifugation and chemical measurement of the very-low-density lipoproteins.", "contents": "The beta-lipoprotein doublet in type 3 hyperlipoproteinemia. We used a previously reported agarose-gel electrophoresis system to study the lipoprotein patterns in patients with type 3 hyperlipoproteinemia. All samples from 20 subjects tested revealed the presence of two bands with beta-lipoprotein mobility, irrespective of quantitative changes in plasma lipids induced by diet or by the administration of drugs. If these observations are confirmed, the method will permit the diagnosis of type 3 hyperlipoproteinemia without resort to preparative ultracentrifugation and chemical measurement of the very-low-density lipoproteins."}
{"id": "PMID:192491", "title": "Effect of glucagon infusion on plasma cyclic AMP in patients with cholestatic hepatitis and obstructive jaundice. New test of hepatic cholestasis.", "content": "Plasma cyclic AMP concentration during glucagon infusion at various time intervals was determined in 8 normal subjects, 9 patients with extrahepatic obstructive jaundice and 10 patients with cholestatic hepatitis (hepatitis A and B). Plasma cyclic AMP concentrations (pmol/ml) during glucagon infusion in patients with both obstructive jaundice and cholestatic hepatitis were found to be greater than those in control subjects. In addition, a significant difference in plasma cyclic AMP concentrations was found between patients with cholestatic hepatitis and obstructive jaundice at the 10th minute of glucagon infusion. These results indicate that plasma cyclic AMP levels at the 10th minute of glucagon infusion represent a reliable diagnostic index of cholestatic jaundice.", "contents": "Effect of glucagon infusion on plasma cyclic AMP in patients with cholestatic hepatitis and obstructive jaundice. New test of hepatic cholestasis. Plasma cyclic AMP concentration during glucagon infusion at various time intervals was determined in 8 normal subjects, 9 patients with extrahepatic obstructive jaundice and 10 patients with cholestatic hepatitis (hepatitis A and B). Plasma cyclic AMP concentrations (pmol/ml) during glucagon infusion in patients with both obstructive jaundice and cholestatic hepatitis were found to be greater than those in control subjects. In addition, a significant difference in plasma cyclic AMP concentrations was found between patients with cholestatic hepatitis and obstructive jaundice at the 10th minute of glucagon infusion. These results indicate that plasma cyclic AMP levels at the 10th minute of glucagon infusion represent a reliable diagnostic index of cholestatic jaundice."}
{"id": "PMID:192492", "title": "Urinary cyclic AMP and post-traumatic acute renal failure.", "content": "Consecutive daily urinary excretion of cyclic AMP has been investigated in 16 patients with severe trauma or illness, five of whom developed acute renal failure (ARF). Fluctuations in the nucleotide excretion exceeded the range found in 20 healthy volunteers (1.26-14.74, mean 7.13+/-1.18 vs. 2.04-10.10, mean 5.07+/-2.21 micronmol/24 h). This resulted in a 41% increase of cAMP excretion in the group with normal renal function (P less than 0.003) with the highest individual increase of 87%. The excretion usually reached its peak by 24 h after trauma and its lowest value by the third day, (first day vs. third day; 7.82+/-4.23 vs. 3.96+/-2.58 micronmol/24 h, P less than 0.05 for a group of 11 patients), while creatinine clearance remained normal. In four patients with severe ARF, the mean urine volume was above control value but the cAMP excretion was reduced to 3.9 to 14.4% and in one patient with a mild ARF to 60.6%. Creatinine excretion of the group was less reduced than that of cAMP (41.2% vs. 19.6%, resp.). cAMP excretion declined proportionally with diminishing creatinine clearance. In the category of 33-65 ml/min it decreased by 33.4% to 3.39 micronmol+/-1.16 micronmol/24 h. cAMP/creatinine ratio proved to be a less sensitive indicator than cAMP/24 h. Daily output of cAMP and creatinine correlated highly with diuresis in ARF patients, controls (always P less than 0.001) and less in patients with normal renal function (P less than 0.02). Urinary cAMP appears to be a very sensitive and early indicator of the onset of ARF and subsequent recovery. This warrants its further study.", "contents": "Urinary cyclic AMP and post-traumatic acute renal failure. Consecutive daily urinary excretion of cyclic AMP has been investigated in 16 patients with severe trauma or illness, five of whom developed acute renal failure (ARF). Fluctuations in the nucleotide excretion exceeded the range found in 20 healthy volunteers (1.26-14.74, mean 7.13+/-1.18 vs. 2.04-10.10, mean 5.07+/-2.21 micronmol/24 h). This resulted in a 41% increase of cAMP excretion in the group with normal renal function (P less than 0.003) with the highest individual increase of 87%. The excretion usually reached its peak by 24 h after trauma and its lowest value by the third day, (first day vs. third day; 7.82+/-4.23 vs. 3.96+/-2.58 micronmol/24 h, P less than 0.05 for a group of 11 patients), while creatinine clearance remained normal. In four patients with severe ARF, the mean urine volume was above control value but the cAMP excretion was reduced to 3.9 to 14.4% and in one patient with a mild ARF to 60.6%. Creatinine excretion of the group was less reduced than that of cAMP (41.2% vs. 19.6%, resp.). cAMP excretion declined proportionally with diminishing creatinine clearance. In the category of 33-65 ml/min it decreased by 33.4% to 3.39 micronmol+/-1.16 micronmol/24 h. cAMP/creatinine ratio proved to be a less sensitive indicator than cAMP/24 h. Daily output of cAMP and creatinine correlated highly with diuresis in ARF patients, controls (always P less than 0.001) and less in patients with normal renal function (P less than 0.02). Urinary cAMP appears to be a very sensitive and early indicator of the onset of ARF and subsequent recovery. This warrants its further study."}
{"id": "PMID:192493", "title": "Comparison of plasma hormonal levels between heroin-addicted and normal subjects.", "content": "The serum concentrations of ACTH, cortisol, aldosterone, thyroxine, cyclic AMP and cholesterol were compared between normal and heroin-addicted subjects. Significantly lower ACTH, cyclic AMP and cholesterol levels were observed to be associated with the heroin addicts, but their plasma thyroxine level was significantly elevated. The possible physiopsychological effect resulting from these changes is discussed.", "contents": "Comparison of plasma hormonal levels between heroin-addicted and normal subjects. The serum concentrations of ACTH, cortisol, aldosterone, thyroxine, cyclic AMP and cholesterol were compared between normal and heroin-addicted subjects. Significantly lower ACTH, cyclic AMP and cholesterol levels were observed to be associated with the heroin addicts, but their plasma thyroxine level was significantly elevated. The possible physiopsychological effect resulting from these changes is discussed."}
{"id": "PMID:192494", "title": "Electrophoretic mobility in agarose of very low density lipoprotein subfractions in type III hyperlipoproteinaemia.", "content": "The electrophoretic mobilities in agarose gel of the very low density lipoprotein (VLDL) subfractions of Sf greater than 100, 60-100 and 20-60 from six subjects with type III hyperlipoproteinaemia (HLP) have been compared with those from eight normal volunteers. In type III HLP beta or near-beta (slower VLDL) electrophoretic mobility was not necessarily confined to the VLDL fraction of Sf 20-60 in which it may normally be detected.", "contents": "Electrophoretic mobility in agarose of very low density lipoprotein subfractions in type III hyperlipoproteinaemia. The electrophoretic mobilities in agarose gel of the very low density lipoprotein (VLDL) subfractions of Sf greater than 100, 60-100 and 20-60 from six subjects with type III hyperlipoproteinaemia (HLP) have been compared with those from eight normal volunteers. In type III HLP beta or near-beta (slower VLDL) electrophoretic mobility was not necessarily confined to the VLDL fraction of Sf 20-60 in which it may normally be detected."}
{"id": "PMID:192495", "title": "Collagenase activity of rat kidney with glomerulonephritis during the heterologous phase.", "content": "By means of a biological assay the collagenolytic activity of kidneys from rats with Masugi type glomerulonephritis in the heterologous phase and organs from control animals that were given normal heterologous serum was tested. Collagenolysis was found in both examples, but there wre quantitative and qualitative differences in the collagenase activity. In kidneys from animals with Masugi nephritis we found higher activity than in the controls. Normal rat serum inhibits the enzymatic process at a mean percentage of 9.1% whereas EDTA, a selective inhibitor of granulocytic collagenase inhibited the reaction up to 34%. It is concluded that this collagenolytic system is involved in the pathogenesis of the disease by degrading the structural associated collagen of the glomerular basement membrane.", "contents": "Collagenase activity of rat kidney with glomerulonephritis during the heterologous phase. By means of a biological assay the collagenolytic activity of kidneys from rats with Masugi type glomerulonephritis in the heterologous phase and organs from control animals that were given normal heterologous serum was tested. Collagenolysis was found in both examples, but there wre quantitative and qualitative differences in the collagenase activity. In kidneys from animals with Masugi nephritis we found higher activity than in the controls. Normal rat serum inhibits the enzymatic process at a mean percentage of 9.1% whereas EDTA, a selective inhibitor of granulocytic collagenase inhibited the reaction up to 34%. It is concluded that this collagenolytic system is involved in the pathogenesis of the disease by degrading the structural associated collagen of the glomerular basement membrane."}
{"id": "PMID:192496", "title": "[Activators for sphingohydrolases and the nature of the sphingomyelinase deficiency in Niemann-Pick disease types A, B and C (author's transl)].", "content": "Sphingomyelinase activities have been assayed either in the presence of detergents or by an activator method, in control subjects and patients with Niemann-Pick disease types A, B and C. The activity of this enzyme assayed with detergents compared with that for control subjects is markedly reduced in Niemann-Pick disease types A or B but not in type C. With the activator method, the enzymic activity is strongly reduced in patients with type C (30%) of the control data). This paper describes a reasonably satisfactory method for enzymic diagnosis of Niemann-Pick disease type C. Hypotheses for enzymic mutations in these three types of Niemann-Pick disease are put forward.", "contents": "[Activators for sphingohydrolases and the nature of the sphingomyelinase deficiency in Niemann-Pick disease types A, B and C (author's transl)]. Sphingomyelinase activities have been assayed either in the presence of detergents or by an activator method, in control subjects and patients with Niemann-Pick disease types A, B and C. The activity of this enzyme assayed with detergents compared with that for control subjects is markedly reduced in Niemann-Pick disease types A or B but not in type C. With the activator method, the enzymic activity is strongly reduced in patients with type C (30%) of the control data). This paper describes a reasonably satisfactory method for enzymic diagnosis of Niemann-Pick disease type C. Hypotheses for enzymic mutations in these three types of Niemann-Pick disease are put forward."}
{"id": "PMID:192497", "title": "Low density lipoproteins and immunoglobulins in human pleural effusions.", "content": "Pleural effusions in patients with bacterial pleurisy contain low density lipoproteins (33 per cent of the blood serum LDL-concentration on average) but almost no very-low density lipoproteins (about 1 percent of the blood serum VLDL-concentration on average). Immunoglobulins are present in large amounts forming a series declining from the IgG (70 per cent of the blood serum concentration, found in effusions) to the IgM (50 per cent of the blood serum concentration). The observations are discussed in relation to morphological aspects of molecular transport through the capillary wall, and the consequences of the LDL- and IgL-accumulation in pleural fluids are briefly discussed.", "contents": "Low density lipoproteins and immunoglobulins in human pleural effusions. Pleural effusions in patients with bacterial pleurisy contain low density lipoproteins (33 per cent of the blood serum LDL-concentration on average) but almost no very-low density lipoproteins (about 1 percent of the blood serum VLDL-concentration on average). Immunoglobulins are present in large amounts forming a series declining from the IgG (70 per cent of the blood serum concentration, found in effusions) to the IgM (50 per cent of the blood serum concentration). The observations are discussed in relation to morphological aspects of molecular transport through the capillary wall, and the consequences of the LDL- and IgL-accumulation in pleural fluids are briefly discussed."}
{"id": "PMID:192498", "title": "Thyroxine binding globulin deficiency in a family with type I hyperlipoproteinaemia.", "content": "A familial type I hyperlipoproteinaemia is described in three members of a family of eleven; on the basis of LPL activity and HDL content of plasma three other members of the family have been diagnosed to be heterozygotes without other disturbances in their lipid spectrum. The distribution of this lipid disorder is in accordance with an autosomal recessive inheritance pattern. In this family a second hereditary condition, thyroxine binding globulin deficiency, was found in addition to the hyperlipoproteinaemia. The inheritance of this condition appears to be as an autosomal dominant. An interrelated inheritance pattern of both conditions could not be proved, but both traits may be located on the same chromosome at some distance from another to allow recombination.", "contents": "Thyroxine binding globulin deficiency in a family with type I hyperlipoproteinaemia. A familial type I hyperlipoproteinaemia is described in three members of a family of eleven; on the basis of LPL activity and HDL content of plasma three other members of the family have been diagnosed to be heterozygotes without other disturbances in their lipid spectrum. The distribution of this lipid disorder is in accordance with an autosomal recessive inheritance pattern. In this family a second hereditary condition, thyroxine binding globulin deficiency, was found in addition to the hyperlipoproteinaemia. The inheritance of this condition appears to be as an autosomal dominant. An interrelated inheritance pattern of both conditions could not be proved, but both traits may be located on the same chromosome at some distance from another to allow recombination."}
{"id": "PMID:192503", "title": "Variable X-linked recessive hypopituitarism with evidence of gonadotropin deficiency in two pre-pubertal males.", "content": "Two half-brothers with short stature secondary to growth hormone deficiency and a family history implicating X-linked transmission were studied extensively for other endocrine abnormalities. The proband had a normal physical examination, except for small stature and small external genitalia. ACTH and TSH release were normal. LH and FSH responses during an i.v. GnRH test were severely blunted. His half-brother also had a normal physical examination, except for severe short stature and very small external genitalia. Deficiencies of ACTH, and TSH as well as GH were documented. An i.v. GnRH test showed no LH or FSH response. These studies support the existence of an X-linked recessive form of hypopituitarism and portend the clinical usefulness of the i.v. GnRH test in evaluating gonadotropin reserve.", "contents": "Variable X-linked recessive hypopituitarism with evidence of gonadotropin deficiency in two pre-pubertal males. Two half-brothers with short stature secondary to growth hormone deficiency and a family history implicating X-linked transmission were studied extensively for other endocrine abnormalities. The proband had a normal physical examination, except for small stature and small external genitalia. ACTH and TSH release were normal. LH and FSH responses during an i.v. GnRH test were severely blunted. His half-brother also had a normal physical examination, except for severe short stature and very small external genitalia. Deficiencies of ACTH, and TSH as well as GH were documented. An i.v. GnRH test showed no LH or FSH response. These studies support the existence of an X-linked recessive form of hypopituitarism and portend the clinical usefulness of the i.v. GnRH test in evaluating gonadotropin reserve."}
{"id": "PMID:192504", "title": "Heterogeneity in maple syrup urine disease: aspects of cofactor requirement and complementation in cultured fibroblasts.", "content": "Fibroblast strains derived from six patients with maple syrup urine disease have been investigated for their requirements of the cofactors NAD, CoASH, Mg++ and TPP in comparison with 10 normal control strains. The reconstitution of the decarboxylase function of branched chain alpha-keto acid (BCKA) dehydrogenase complex in lysed cells was studied with respect to the substrates alpha-keto-isocaproic acid, alpha-keto-isovaleric acid, and alpha-keto-beta-methylvaleric acid (KIC, KIVA, MEVA). The enzyme activity of all normal control strains for the substrates KIC and KIVA was not reconstituted by TPP + Mg++ alone, but CoASH + NAD could reconstitute the enzyme activity with KIC and KIVA in different degrees. Only two control strains were tested with MEVA as substrate, and these showed in contrast that TPP + Mg++ could partly reconstitute the enzyme activity. In contrast to the relative homogeneity in the reconstitution profiles of normal strains, the five classical and one intermittent MSUD strains showed heterogeneity in cofactor requirements. Complementation analysis using heterokaryons prepared from fibroblasts of four patients with classical MSUD and one patient with intermittent MSUD showed, in contrast to experiments with normal controls, a partial amelioration of the defect in two combinations; it is suggested that the defect in these strains is located at different functional subunits of the multienzyme complex.", "contents": "Heterogeneity in maple syrup urine disease: aspects of cofactor requirement and complementation in cultured fibroblasts. Fibroblast strains derived from six patients with maple syrup urine disease have been investigated for their requirements of the cofactors NAD, CoASH, Mg++ and TPP in comparison with 10 normal control strains. The reconstitution of the decarboxylase function of branched chain alpha-keto acid (BCKA) dehydrogenase complex in lysed cells was studied with respect to the substrates alpha-keto-isocaproic acid, alpha-keto-isovaleric acid, and alpha-keto-beta-methylvaleric acid (KIC, KIVA, MEVA). The enzyme activity of all normal control strains for the substrates KIC and KIVA was not reconstituted by TPP + Mg++ alone, but CoASH + NAD could reconstitute the enzyme activity with KIC and KIVA in different degrees. Only two control strains were tested with MEVA as substrate, and these showed in contrast that TPP + Mg++ could partly reconstitute the enzyme activity. In contrast to the relative homogeneity in the reconstitution profiles of normal strains, the five classical and one intermittent MSUD strains showed heterogeneity in cofactor requirements. Complementation analysis using heterokaryons prepared from fibroblasts of four patients with classical MSUD and one patient with intermittent MSUD showed, in contrast to experiments with normal controls, a partial amelioration of the defect in two combinations; it is suggested that the defect in these strains is located at different functional subunits of the multienzyme complex."}
{"id": "PMID:192505", "title": "Herpesnephropathy.", "content": "Two cases of acute renal insufficiency occurred in association with episodes of severe encephalitis due to herpes simplex type I. The possibility was considered that the renal failure was due to viral infection of the kidneys, and animal experiments were carried out in an attempt to confirm this. Young New Zealand albino rabbits were infected i. v. with HSV type I; the virus antigen was detected in the kidney of 8 of 10 animals, and IgG was found on the GBM in 9 of 19 animals. Viruria was observed in 12 of the 29 infected animals, and electronmicroscopic examination confirmed the presence of immune complexes in the glomeruli.", "contents": "Herpesnephropathy. Two cases of acute renal insufficiency occurred in association with episodes of severe encephalitis due to herpes simplex type I. The possibility was considered that the renal failure was due to viral infection of the kidneys, and animal experiments were carried out in an attempt to confirm this. Young New Zealand albino rabbits were infected i. v. with HSV type I; the virus antigen was detected in the kidney of 8 of 10 animals, and IgG was found on the GBM in 9 of 19 animals. Viruria was observed in 12 of the 29 infected animals, and electronmicroscopic examination confirmed the presence of immune complexes in the glomeruli."}
{"id": "PMID:192506", "title": "Oestrogens and endometrial cancer: a point of view.", "content": "The medical profession has been disturbed and bewildered by a number of recent communications which discussed a possible relationship between contraceptive sequential therapy and the incidence of endometrial cancer and between the postmenopausal application of conjugated oestrogens and endometrial carcinoma. An analysis of these reports is made critically and in detail and supplemented with observations on the risk of carcinoma of the breast. The practical aspects are delineated and a precise guide to postmenopausal oestrogen therapy presented.", "contents": "Oestrogens and endometrial cancer: a point of view. The medical profession has been disturbed and bewildered by a number of recent communications which discussed a possible relationship between contraceptive sequential therapy and the incidence of endometrial cancer and between the postmenopausal application of conjugated oestrogens and endometrial carcinoma. An analysis of these reports is made critically and in detail and supplemented with observations on the risk of carcinoma of the breast. The practical aspects are delineated and a precise guide to postmenopausal oestrogen therapy presented."}
{"id": "PMID:192508", "title": "Electron spin resonance as a useful technique in the management of Hodgkin's disease.", "content": "Electron spin resonance spectroscopy has proved a useful and simple technique for the measurement of levels of caeruloplasmin and iron transferrin in whole blood from 50 patients with Hodgkin's disease. Those patients with clinically active disease show higher caeruloplasmin levels and lower iron transferrin levels than those with inactive disease. The results indicate that these tests are good indicators of the state of the disease and that serial measurement of these parameters may help in early prediction of clinical reactivity and in monitoring response to treatment. The combined information from iron transferrin and caeruloplasmin levels appears to be more predictive than that from the erythrocyte sedimentation rate and neutrophil alkaline phosphatase score.", "contents": "Electron spin resonance as a useful technique in the management of Hodgkin's disease. Electron spin resonance spectroscopy has proved a useful and simple technique for the measurement of levels of caeruloplasmin and iron transferrin in whole blood from 50 patients with Hodgkin's disease. Those patients with clinically active disease show higher caeruloplasmin levels and lower iron transferrin levels than those with inactive disease. The results indicate that these tests are good indicators of the state of the disease and that serial measurement of these parameters may help in early prediction of clinical reactivity and in monitoring response to treatment. The combined information from iron transferrin and caeruloplasmin levels appears to be more predictive than that from the erythrocyte sedimentation rate and neutrophil alkaline phosphatase score."}
{"id": "PMID:192509", "title": "Electron spin resonance measurements of blood caeruloplasmin and iron transferrin levels in patients with non-Hodgkin's lymphoma.", "content": "Caeruloplasmin and iron transferrin level were measured in blood of patients with non-Hodgkin's lymphoma in different stages of disease activity and compared with erythrocyte sedimentation rate and NAP level in the same samples. It was found that both caeruloplasmin level and sedimentation rate showed a slight increase in mean level in patients with active disease as compared with those in remission, particularly in the group of patients with poorly or undifferentiated diffuse disease. No difference was observed in levels of iron transferrin or NAP. Both caeruloplasmin and sedimentation rate showed occasional abnormal values in patients in remission but in most cases where both were elevated the patients subsequently entered a more active phase of the disease.", "contents": "Electron spin resonance measurements of blood caeruloplasmin and iron transferrin levels in patients with non-Hodgkin's lymphoma. Caeruloplasmin and iron transferrin level were measured in blood of patients with non-Hodgkin's lymphoma in different stages of disease activity and compared with erythrocyte sedimentation rate and NAP level in the same samples. It was found that both caeruloplasmin level and sedimentation rate showed a slight increase in mean level in patients with active disease as compared with those in remission, particularly in the group of patients with poorly or undifferentiated diffuse disease. No difference was observed in levels of iron transferrin or NAP. Both caeruloplasmin and sedimentation rate showed occasional abnormal values in patients in remission but in most cases where both were elevated the patients subsequently entered a more active phase of the disease."}
{"id": "PMID:192510", "title": "The nature of the beta-adrenoreceptor controlling plasma renin activity in man.", "content": "1. Seven healthy sodium-replete male volunteer subjects remained supine during and for at least 1 h before the study. Heart rate and blood pressure were recorded continuously, and peripheral venous blood samples were taken every 15 min for determinations of plasma renin activity. 2. All subjects were studied twice: after 3 days of oral practolol (100 mg, three times daily) and after a similar period on placebo. Each study consisted of an intravenous infusion of isoprenaline in graded doses (0-20 microng/min in the placebo phase; 0-16 microng/min in the practolol phase), followed after rest for 2 h by an intravenous infusion of salbutamol (0-20 microng/min after placebo; 0-80 microng/min after practolol). 3. Both salbutamol and isoprenaline produced dose-related increases in systolic blood pressure, heart rate and plasma renin activity and decreases in diastolic pressure. 4. The increases in heart rate and plasma renin activity induced by either agonist were competitively blocked by practolol, as was the fall in diastolic blood pressure induced by isoprenaline; the salbutamol-induced fall of diastolic blood pressure was unaffected by practolol. 5. Comparison of dose ratio--1 estimates confirmed that practolol selectively blocked increases in heart rate and plasma renin activity due to salbutamol; no selective blockade against isoprenaline-induced changes was shown. 6. Selective blockade of salbutamol-induced changes indicate that a beta1-adrenoreceptor mediates changes in plasma renin activity.", "contents": "The nature of the beta-adrenoreceptor controlling plasma renin activity in man. 1. Seven healthy sodium-replete male volunteer subjects remained supine during and for at least 1 h before the study. Heart rate and blood pressure were recorded continuously, and peripheral venous blood samples were taken every 15 min for determinations of plasma renin activity. 2. All subjects were studied twice: after 3 days of oral practolol (100 mg, three times daily) and after a similar period on placebo. Each study consisted of an intravenous infusion of isoprenaline in graded doses (0-20 microng/min in the placebo phase; 0-16 microng/min in the practolol phase), followed after rest for 2 h by an intravenous infusion of salbutamol (0-20 microng/min after placebo; 0-80 microng/min after practolol). 3. Both salbutamol and isoprenaline produced dose-related increases in systolic blood pressure, heart rate and plasma renin activity and decreases in diastolic pressure. 4. The increases in heart rate and plasma renin activity induced by either agonist were competitively blocked by practolol, as was the fall in diastolic blood pressure induced by isoprenaline; the salbutamol-induced fall of diastolic blood pressure was unaffected by practolol. 5. Comparison of dose ratio--1 estimates confirmed that practolol selectively blocked increases in heart rate and plasma renin activity due to salbutamol; no selective blockade against isoprenaline-induced changes was shown. 6. Selective blockade of salbutamol-induced changes indicate that a beta1-adrenoreceptor mediates changes in plasma renin activity."}
{"id": "PMID:192511", "title": "Noradrenaline sensitivity of an isolated perfused artery: effects of normal and hypertensive plasma.", "content": "1. The noradrenaline sensitivity of the isolated perfused rabbit artery was studied, during perfusion with Krebs solution, normal plasma, hypertensive plasma and a low-density lipoprotein (LDL) extract of normal plasma. 2. There was no difference in noradrenaline sensitivity between arteries perfused with Krebs and normal plasma. 3. Both hypertensive plasma and LDL potentiated the noradrenaline-induced vasoconstriction. 4. This potentiation was associated with increases in both the intrinsic activity of the drug-receptor complex and the drug-receptor affinity. 5. There is a circulating factor in the plasma of hypertensive patients which sensitizes arteries to noradrenaline, and this factor may be LDL.", "contents": "Noradrenaline sensitivity of an isolated perfused artery: effects of normal and hypertensive plasma. 1. The noradrenaline sensitivity of the isolated perfused rabbit artery was studied, during perfusion with Krebs solution, normal plasma, hypertensive plasma and a low-density lipoprotein (LDL) extract of normal plasma. 2. There was no difference in noradrenaline sensitivity between arteries perfused with Krebs and normal plasma. 3. Both hypertensive plasma and LDL potentiated the noradrenaline-induced vasoconstriction. 4. This potentiation was associated with increases in both the intrinsic activity of the drug-receptor complex and the drug-receptor affinity. 5. There is a circulating factor in the plasma of hypertensive patients which sensitizes arteries to noradrenaline, and this factor may be LDL."}
{"id": "PMID:192512", "title": "Isolation of renal membranes that contain kallikrein, angiotensin I-converting enzyme (kininase II) and angiotensinase in the rat.", "content": "1. Fractions highly enriched in plasma membrane, endoplasmic reticulum or brush border were prepared from rat kidney cortex. Kallikrein was concentrated in the plasma membrane fraction, but not in the brush border fraction. Angiotensin I-converting enzyme (kininase II) and angiotensinase were localized in the brush border membrane. 2. It is suggested that kallikrein in the urine may originate from plasma membrane distal to the brush border of proximal tubules and the conversion of angiotensin I and the inactivation of bradykinin and angiotensin II may occur on the lumen membrane of the proximal tubular cells.", "contents": "Isolation of renal membranes that contain kallikrein, angiotensin I-converting enzyme (kininase II) and angiotensinase in the rat. 1. Fractions highly enriched in plasma membrane, endoplasmic reticulum or brush border were prepared from rat kidney cortex. Kallikrein was concentrated in the plasma membrane fraction, but not in the brush border fraction. Angiotensin I-converting enzyme (kininase II) and angiotensinase were localized in the brush border membrane. 2. It is suggested that kallikrein in the urine may originate from plasma membrane distal to the brush border of proximal tubules and the conversion of angiotensin I and the inactivation of bradykinin and angiotensin II may occur on the lumen membrane of the proximal tubular cells."}
{"id": "PMID:192513", "title": "Functional-morphological correlates of renomedullary interstitial cells.", "content": "1. Indomethacin treatment of renomedullary interstitial cells (RIC) causes a marked increase in number and size of their lipid droplets. The anti-hypertensive function is retained. 2. After multiple passages in tissue culture, RIC lose their ability to produce an anti-hypertensive effect in hypertensive animals. Along with this functional loss, lipid droplets and a prominent cisternal system become attenuated or disappear. 3. We conclude that preservation of the lipid granule-cisternal organelle relationship is important in preservation of the anti-hypertensive endocrine function of RIC.", "contents": "Functional-morphological correlates of renomedullary interstitial cells. 1. Indomethacin treatment of renomedullary interstitial cells (RIC) causes a marked increase in number and size of their lipid droplets. The anti-hypertensive function is retained. 2. After multiple passages in tissue culture, RIC lose their ability to produce an anti-hypertensive effect in hypertensive animals. Along with this functional loss, lipid droplets and a prominent cisternal system become attenuated or disappear. 3. We conclude that preservation of the lipid granule-cisternal organelle relationship is important in preservation of the anti-hypertensive endocrine function of RIC."}
{"id": "PMID:192514", "title": "Further unravelling of the causes of ACTH-induced hypertension in the sheep.", "content": "1. Acute severe sodium subtraction (20-25% of total exchangeable sodium) before or during treatment with adrenocorticotrophic hormone (ACTH) does little to modify the increase in blood pressure induced by ACTH. 2. Chronic low salt diet, less than 5 mmol/day, abolishes the blood pressure increase, but the response can be restored by increasing the sodium intake to as little as 10 mmol/day. 3. 17alpha,20alpha-Dihydroxyprogesterone infused concurrently with other adrenal steroids will mimic ACTH hypertension and perhaps represents a new class of steroid capable of influencing blood pressure.", "contents": "Further unravelling of the causes of ACTH-induced hypertension in the sheep. 1. Acute severe sodium subtraction (20-25% of total exchangeable sodium) before or during treatment with adrenocorticotrophic hormone (ACTH) does little to modify the increase in blood pressure induced by ACTH. 2. Chronic low salt diet, less than 5 mmol/day, abolishes the blood pressure increase, but the response can be restored by increasing the sodium intake to as little as 10 mmol/day. 3. 17alpha,20alpha-Dihydroxyprogesterone infused concurrently with other adrenal steroids will mimic ACTH hypertension and perhaps represents a new class of steroid capable of influencing blood pressure."}
{"id": "PMID:192515", "title": "Aldosterone regulation in primary aldosteronism: differences between adenoma and bilateral hyperplasia.", "content": "1. The diurnal patterns of plasma aldosterone, plasma renin activity (PRA), cortisol and adrenocorticotrophic hormone (ACTH) in the supine and in the upright position have been studied in fourteen patients with primary aldosteronism, five with adenoma and nine with bilateral hyperplasia. Blood samples were drawn at intervals from 6 h to 30 min. 2. Supine patients with an adenoma showed marked diurnal variations of aldosterone, with maximal values at 08.00 hours and minimal values of 18.00 hours and secretory spurts beginning after 02.00 hours. Plasma cortisol paralleled aldosterone, and ACTH seemed to anticipate aldosterone and cortisol variations; PRA remained unchanged. In patients with hyperplasia, aldosterone was significantly lower than in the adenoma group at 08.00 hours, and its decline during the day was less marked; fluctuations rather than secretory episodes were seen. 3. After patients assumed the upright posture, aldosterone remained unchanged or decreased in patients with adenoma, whereas it significantly increased in hyperplasia; PRA remained low, although a slight increment was seen in the latter group. The different response of aldosterone in the two groups was not modified by the administration of propranolol, apparently excluding a renin-dependent mechanism. On the other hand, dexamethasone seemed to affect the response of aldosterone to the upright posture in both groups; in adenoma there was a slight but significant increase, and in hyperplasia the usual rise was partially suppressed. 4. It is concluded that ACTH has a predominant role in regulating aldosterone secretion in primary aldosteronism due to adenoma, whereas its action in bilateral hyperplasia is only permissive.", "contents": "Aldosterone regulation in primary aldosteronism: differences between adenoma and bilateral hyperplasia. 1. The diurnal patterns of plasma aldosterone, plasma renin activity (PRA), cortisol and adrenocorticotrophic hormone (ACTH) in the supine and in the upright position have been studied in fourteen patients with primary aldosteronism, five with adenoma and nine with bilateral hyperplasia. Blood samples were drawn at intervals from 6 h to 30 min. 2. Supine patients with an adenoma showed marked diurnal variations of aldosterone, with maximal values at 08.00 hours and minimal values of 18.00 hours and secretory spurts beginning after 02.00 hours. Plasma cortisol paralleled aldosterone, and ACTH seemed to anticipate aldosterone and cortisol variations; PRA remained unchanged. In patients with hyperplasia, aldosterone was significantly lower than in the adenoma group at 08.00 hours, and its decline during the day was less marked; fluctuations rather than secretory episodes were seen. 3. After patients assumed the upright posture, aldosterone remained unchanged or decreased in patients with adenoma, whereas it significantly increased in hyperplasia; PRA remained low, although a slight increment was seen in the latter group. The different response of aldosterone in the two groups was not modified by the administration of propranolol, apparently excluding a renin-dependent mechanism. On the other hand, dexamethasone seemed to affect the response of aldosterone to the upright posture in both groups; in adenoma there was a slight but significant increase, and in hyperplasia the usual rise was partially suppressed. 4. It is concluded that ACTH has a predominant role in regulating aldosterone secretion in primary aldosteronism due to adenoma, whereas its action in bilateral hyperplasia is only permissive."}
{"id": "PMID:192516", "title": "Selective hypoaldosteronism: a study of steroid biosynthetic pathways under adrenocorticotrophin and angiotensin II infusion.", "content": "1. The functional integrity of the adrenal cortex has been tested in a case of selective hypoaldosteronism by adrenocorticotrophin (ACTH) and angiotensin II (AII) infusion. 2. During ACTH infusion a normal functioning zona fasciculata was indicated by the impressive increase of the ACTH-dependent plasma steroids; the aldosterone response was moderate. 3. During AII infusion the plasma aldosterone response was blunted with an unexpected dose-dependent increase in pregnenolone, resulting in abnormal decreasing progesterone/pregnenolone ratios during the infusion, suggesting a slow-down in the conversion of pregnenolone into progesterone. 4. This defect, a probable consequence of chronic renin deficiency on the zona glomerulosa, could be a contributing factor to the hypoaldosteronism.", "contents": "Selective hypoaldosteronism: a study of steroid biosynthetic pathways under adrenocorticotrophin and angiotensin II infusion. 1. The functional integrity of the adrenal cortex has been tested in a case of selective hypoaldosteronism by adrenocorticotrophin (ACTH) and angiotensin II (AII) infusion. 2. During ACTH infusion a normal functioning zona fasciculata was indicated by the impressive increase of the ACTH-dependent plasma steroids; the aldosterone response was moderate. 3. During AII infusion the plasma aldosterone response was blunted with an unexpected dose-dependent increase in pregnenolone, resulting in abnormal decreasing progesterone/pregnenolone ratios during the infusion, suggesting a slow-down in the conversion of pregnenolone into progesterone. 4. This defect, a probable consequence of chronic renin deficiency on the zona glomerulosa, could be a contributing factor to the hypoaldosteronism."}
{"id": "PMID:192520", "title": "Cadmium-induced proximal tubular dysfunction in a cadmium-polluted area.", "content": "Health examinations were performed in 147 people living in a cadmium-polluted area, Kosaka Town, Japan. 33 of 147 residents had some indications of proximal tubular dysfunction, such as renal glucosuria, tubular proteinuria, and aminoaciduria, and 10 of them were diagnosed as having multiple proximal tubular dysfunctions. Detailed examinations revealed that none of the cases had any causal diseases other than chronic cadmium poisoning. Residents' mean cadmium intake and mean urinary cadmium concentration were over 3 times as high as those in control areas. From these findings, renal lesions identified in these residents were concluded as chronic cadmium poisoning induced by environmental cadmium pollution.", "contents": "Cadmium-induced proximal tubular dysfunction in a cadmium-polluted area. Health examinations were performed in 147 people living in a cadmium-polluted area, Kosaka Town, Japan. 33 of 147 residents had some indications of proximal tubular dysfunction, such as renal glucosuria, tubular proteinuria, and aminoaciduria, and 10 of them were diagnosed as having multiple proximal tubular dysfunctions. Detailed examinations revealed that none of the cases had any causal diseases other than chronic cadmium poisoning. Residents' mean cadmium intake and mean urinary cadmium concentration were over 3 times as high as those in control areas. From these findings, renal lesions identified in these residents were concluded as chronic cadmium poisoning induced by environmental cadmium pollution."}
{"id": "PMID:192521", "title": "Orderly bioelectric phenomena and myelin integrity: an hypothesis.", "content": "The classical approach to myelin function, in light of current data, is deemed inadequate. Electron microscopic data is used to support the novel hypothesis of interneuronal communication at nodes of Ranvier in the central nervous system of higher organisms. It is hypothesized that myelin plays a role in imposing order hypothesis, use is made of both developmental and degenerative aspects of myelin.", "contents": "Orderly bioelectric phenomena and myelin integrity: an hypothesis. The classical approach to myelin function, in light of current data, is deemed inadequate. Electron microscopic data is used to support the novel hypothesis of interneuronal communication at nodes of Ranvier in the central nervous system of higher organisms. It is hypothesized that myelin plays a role in imposing order hypothesis, use is made of both developmental and degenerative aspects of myelin."}
{"id": "PMID:192530", "title": "1-alpha-acetylmethadol (LAAM), methadone and morphine abstinence in dependent rats: EEG and behavioral correlates.", "content": "Adult female Sprague-Dawley rats were prepared with chronic intravenous cannulas and cortical and muscle electrodes for recording electroencephalograms and electromyograms, respectively. They were made physically dependent on morphine by automatic intravenous injections and then trained to lever press in order to self-administer morphine on a FR-20 schedule of reinforcement. Upon stabilization of morphine self-administration, one group continued to self-administer morphine, while two other groups were switched to methadone or 1-alpha-acetylmethadol (LAAM) self-administration for an additional five to ten days. Continuous EEG and EMG recordings were collected. Initially, automatic injections of morphine suppressed rapid eye movement (REM) sleep time, then tolerance developed to this effect. REM sleep time in rats self-administering LAAM, methadone or morphine was within the lower limit of the normal range. Following withdrawal, REM sleep was severely suppressed during the first 24 h with morphine and methadone, but only moderately suppressed with LAAM. Increases in lever pressing during withdrawal from morphine and methadone occurred earlier and were more intense and prolonged than for LAAM. The incidence of head shakes peaked earlier and was higher for morphine and methadone during withdrawal than for LAAM. Irritability scores increased for morphine and methadone during the first day of withdrawal, but did not show any increase until the third day for LAAM. These findings suggest that in dependent rats withdrawal from LAAM is less severe than withdrawal from morphine or methadone.", "contents": "1-alpha-acetylmethadol (LAAM), methadone and morphine abstinence in dependent rats: EEG and behavioral correlates. Adult female Sprague-Dawley rats were prepared with chronic intravenous cannulas and cortical and muscle electrodes for recording electroencephalograms and electromyograms, respectively. They were made physically dependent on morphine by automatic intravenous injections and then trained to lever press in order to self-administer morphine on a FR-20 schedule of reinforcement. Upon stabilization of morphine self-administration, one group continued to self-administer morphine, while two other groups were switched to methadone or 1-alpha-acetylmethadol (LAAM) self-administration for an additional five to ten days. Continuous EEG and EMG recordings were collected. Initially, automatic injections of morphine suppressed rapid eye movement (REM) sleep time, then tolerance developed to this effect. REM sleep time in rats self-administering LAAM, methadone or morphine was within the lower limit of the normal range. Following withdrawal, REM sleep was severely suppressed during the first 24 h with morphine and methadone, but only moderately suppressed with LAAM. Increases in lever pressing during withdrawal from morphine and methadone occurred earlier and were more intense and prolonged than for LAAM. The incidence of head shakes peaked earlier and was higher for morphine and methadone during withdrawal than for LAAM. Irritability scores increased for morphine and methadone during the first day of withdrawal, but did not show any increase until the third day for LAAM. These findings suggest that in dependent rats withdrawal from LAAM is less severe than withdrawal from morphine or methadone."}
{"id": "PMID:192531", "title": "[Developmental anomalies of the liver and carcinoma of the liver in infants and children (author's transl)].", "content": "Several forms of intrahepatic developmental anomalies were found on histological examination in 40 children, among them several siblings and polyovular twins. These anomalies affect in principle all structural elements of the liver. In several cases--some of them complicated by cholangitis-there was cholangiofibrosis and cholangiodysplastic pseudo-cirrhosis. In addition, in six children there developed hepatocellular carcinoma between the ages of six months and twelve years. In the course of the development of hepatic carcinoma obligatory nodular for occur. They are made up of light, glycogen-loaded epithelial cells, which later are transformed into small atypical, basophilic cells. These dark cells have a high mitosis rate, have already escaped from the physiological regulation of proliferation. Presumably the various embryonic disorders of liver structure and carcinoma of the liver are based on the action of the same causative factor, which may be of chemical-toxic origin and transferred across the placenta.", "contents": "[Developmental anomalies of the liver and carcinoma of the liver in infants and children (author's transl)]. Several forms of intrahepatic developmental anomalies were found on histological examination in 40 children, among them several siblings and polyovular twins. These anomalies affect in principle all structural elements of the liver. In several cases--some of them complicated by cholangitis-there was cholangiofibrosis and cholangiodysplastic pseudo-cirrhosis. In addition, in six children there developed hepatocellular carcinoma between the ages of six months and twelve years. In the course of the development of hepatic carcinoma obligatory nodular for occur. They are made up of light, glycogen-loaded epithelial cells, which later are transformed into small atypical, basophilic cells. These dark cells have a high mitosis rate, have already escaped from the physiological regulation of proliferation. Presumably the various embryonic disorders of liver structure and carcinoma of the liver are based on the action of the same causative factor, which may be of chemical-toxic origin and transferred across the placenta."}
{"id": "PMID:192535", "title": "A-cell behavior in organ culture of isolated rat islets: secretion and tissue content of glucagon and insulin.", "content": "The present study was done to characterize the hormone secretion and content of isolated rat islets in organ culture dependent on the glucose concentration and the number of cultivated islets per culture bottle (10 or 30). For the calculation of the recovery rate the glucagon and insulin breakdown in the culture medium containing 10% calf serum was assayed. The glucagon recovery after incubation for 24 h at 37 degrees C varied from 2 to 92% and that of insulin from 75--105% depending on the serum batches. The cultivated islet responded to 16 mmol glucose by a significant enhancement of insulin release, whereas the glucagon release was not influenced. The glucagon release fell progressively with the duration of cultivation. 2 mmol dibutyryl cyclic AMP augmented insulin and glucagon release in the presence of 5 and 16 mmol glucose and significantly enhanced the glucagon content in the cultivated islets.", "contents": "A-cell behavior in organ culture of isolated rat islets: secretion and tissue content of glucagon and insulin. The present study was done to characterize the hormone secretion and content of isolated rat islets in organ culture dependent on the glucose concentration and the number of cultivated islets per culture bottle (10 or 30). For the calculation of the recovery rate the glucagon and insulin breakdown in the culture medium containing 10% calf serum was assayed. The glucagon recovery after incubation for 24 h at 37 degrees C varied from 2 to 92% and that of insulin from 75--105% depending on the serum batches. The cultivated islet responded to 16 mmol glucose by a significant enhancement of insulin release, whereas the glucagon release was not influenced. The glucagon release fell progressively with the duration of cultivation. 2 mmol dibutyryl cyclic AMP augmented insulin and glucagon release in the presence of 5 and 16 mmol glucose and significantly enhanced the glucagon content in the cultivated islets."}
{"id": "PMID:192536", "title": "Effect of thyroxine and of thyrotropin releasing hormone on cyclic AMP concentration in the anterior pituitary gland in vitro.", "content": "The effect TRH and thyroxine (T4) in vitro on the content of cAMP in the anterior pituitary gland in rat have been investigated. Thyroxine did not significantly affect this concentration, but TRH produced approximately a two-fold increase in the pituitary cAMP content. Preincubation of the anterior pituitary together with T4--under the conditions when the latter inhibited both proliferative and secretory response of the gland to TRH--did not prevent the elevation of cAMP due to TRH. It is assumed that T4 must have exerted its inhibitory effect outside of the cyclic AMP system.", "contents": "Effect of thyroxine and of thyrotropin releasing hormone on cyclic AMP concentration in the anterior pituitary gland in vitro. The effect TRH and thyroxine (T4) in vitro on the content of cAMP in the anterior pituitary gland in rat have been investigated. Thyroxine did not significantly affect this concentration, but TRH produced approximately a two-fold increase in the pituitary cAMP content. Preincubation of the anterior pituitary together with T4--under the conditions when the latter inhibited both proliferative and secretory response of the gland to TRH--did not prevent the elevation of cAMP due to TRH. It is assumed that T4 must have exerted its inhibitory effect outside of the cyclic AMP system."}
{"id": "PMID:192537", "title": "Modulation of pituitary thyrotropin releasing hormone receptor levels by estrogens and thyroid hormones.", "content": "The effect of estradiol and thyroid hormone treatment on pituitary TRH binding and TSH and PRL responses to the neurohormone was studied. A significant increase in the number of pituitary TRH binding sites was observed between 2 and 4 days after daily administration of estradiol benzoate with a plateau at 300% of control being reached at 7 days. Plasma PRL levels showed a similar early pattern of response. In animals rendered hypothyroid by a 2-month treatment with propylthiouracil or 1 month after surgical thyroidectomy, the level of pituitary TRH receptors was increased approximately 2-fold, this elevation being completely reversed by treatment with thyroid hormone. Estradiol-17beta administered with L-thyroxine partially reversed the inhibitory effect of thyroid hormone on TRH receptor levels in hypothyroid animals. The antagonism between estrogens and thyroid hormone is also apparent on the TSH response to TRH since estrogen administration can reverse the marked inhibition by thyroxine of the TSH response to TRH either partially or completely in intact and hypothyroid animals, respectively. The PRL response to TRH is 55 and 40% inhibited in hypothyroid and intact rats, respectively, by thyroid hormone when combined with estrogen treatment. The present data clearly show that estrogens and thyroid hormones can affect TSH and PRL secretion, the effect of estrogens being predominantly on PRL secretion while thyroid hormone affects mainly TSH. The close correlation observed between the level of TRH receptors and PRL and TSH responses to TRH suggests that estrogens and, to a lesser extent, thyroid hormones, exert their action by modulation of the level of receptors for the neurohormone in both thyrotrophs and mammotrophs.", "contents": "Modulation of pituitary thyrotropin releasing hormone receptor levels by estrogens and thyroid hormones. The effect of estradiol and thyroid hormone treatment on pituitary TRH binding and TSH and PRL responses to the neurohormone was studied. A significant increase in the number of pituitary TRH binding sites was observed between 2 and 4 days after daily administration of estradiol benzoate with a plateau at 300% of control being reached at 7 days. Plasma PRL levels showed a similar early pattern of response. In animals rendered hypothyroid by a 2-month treatment with propylthiouracil or 1 month after surgical thyroidectomy, the level of pituitary TRH receptors was increased approximately 2-fold, this elevation being completely reversed by treatment with thyroid hormone. Estradiol-17beta administered with L-thyroxine partially reversed the inhibitory effect of thyroid hormone on TRH receptor levels in hypothyroid animals. The antagonism between estrogens and thyroid hormone is also apparent on the TSH response to TRH since estrogen administration can reverse the marked inhibition by thyroxine of the TSH response to TRH either partially or completely in intact and hypothyroid animals, respectively. The PRL response to TRH is 55 and 40% inhibited in hypothyroid and intact rats, respectively, by thyroid hormone when combined with estrogen treatment. The present data clearly show that estrogens and thyroid hormones can affect TSH and PRL secretion, the effect of estrogens being predominantly on PRL secretion while thyroid hormone affects mainly TSH. The close correlation observed between the level of TRH receptors and PRL and TSH responses to TRH suggests that estrogens and, to a lesser extent, thyroid hormones, exert their action by modulation of the level of receptors for the neurohormone in both thyrotrophs and mammotrophs."}
{"id": "PMID:192538", "title": "Changes of pituitary thyrotropin releasing hormone (TRH) receptor level and prolactin response to TRH during the rat estrous cycle.", "content": "The plasma PRL and TSH responses to TRH injected iv at different stages of the estrous cycle in normal rats under Surital anesthesia were maximal during the afternoon of proestrus and morning of estrus and lowest on diestrus I. As calculated from the areas under the plasma response curves, a 10-fold difference was found between the maximal and minimal PRL responses while a 2-fold difference was measured for TSH. The plasma PRL and TSH responses to TRH showed a correlation with the binding of [3H]TRH to anterior pituitary gland, a 3-fold difference being observed between the minimal binding measured on the morning of diestrus II and the maximal value found on the evening of proestrus. Contrary to findings with LHRH and LH, repeated injections of a small dose  (10 ng) of TRH in the afternoon of proestrus abolished PRL and TSH responses to subsequent injection of the neurohormone.", "contents": "Changes of pituitary thyrotropin releasing hormone (TRH) receptor level and prolactin response to TRH during the rat estrous cycle. The plasma PRL and TSH responses to TRH injected iv at different stages of the estrous cycle in normal rats under Surital anesthesia were maximal during the afternoon of proestrus and morning of estrus and lowest on diestrus I. As calculated from the areas under the plasma response curves, a 10-fold difference was found between the maximal and minimal PRL responses while a 2-fold difference was measured for TSH. The plasma PRL and TSH responses to TRH showed a correlation with the binding of [3H]TRH to anterior pituitary gland, a 3-fold difference being observed between the minimal binding measured on the morning of diestrus II and the maximal value found on the evening of proestrus. Contrary to findings with LHRH and LH, repeated injections of a small dose  (10 ng) of TRH in the afternoon of proestrus abolished PRL and TSH responses to subsequent injection of the neurohormone."}
{"id": "PMID:192539", "title": "Triiodothyronine receptors during maturation.", "content": "Capacity of rat liver nuclear triiodothyronine (T3) binding protein (NTBP) for T3 more than quadruples from birth through 50-120 days, whether related to DNA or weight of tissue. Ka for T3 doubles during this interval. T3 content of nuclei nearly parallels capacity. The proportion of receptors occupied by T3 is 0.3 at birth, falling to .16 in old rats. In contrast to these changes in liver content of T3-receptor complex, mitochondrial alpha-glycerophosphate dehydrogenase activity changes relatively less during maturation. Administration of estrogen, testosterone, and dexamethasone to immature female rats did not alter NTBP capacity of affinity.", "contents": "Triiodothyronine receptors during maturation. Capacity of rat liver nuclear triiodothyronine (T3) binding protein (NTBP) for T3 more than quadruples from birth through 50-120 days, whether related to DNA or weight of tissue. Ka for T3 doubles during this interval. T3 content of nuclei nearly parallels capacity. The proportion of receptors occupied by T3 is 0.3 at birth, falling to .16 in old rats. In contrast to these changes in liver content of T3-receptor complex, mitochondrial alpha-glycerophosphate dehydrogenase activity changes relatively less during maturation. Administration of estrogen, testosterone, and dexamethasone to immature female rats did not alter NTBP capacity of affinity."}
{"id": "PMID:192540", "title": "Reevaluation of the role of cyclic adenosine 3',5'-monophosphate and protein kinase in the stimulation of steroidogenesis by luteinizing hormone in bovine corpus luteum slices.", "content": "Incubation of bovine corpus luteum slices at 37 C with luteinizing hormone showed that 10.0 microng LH/ml caused a maximum rise in tissue cyclic AMP content within 15 min. Slices incubated with 1.0 or 0.1 microng LH/ml showed a much more gradual accumulation of this nucleotide. In the absence of added LH, a marked decline in the amount of cyclic AMP was observed during the first 60 min. The possible role of cyclic AMP in the action of LH was reexamined by studying the dose-response effect of LH on the stimulation of progesterone synthesis, cyclic AMP-dependent protein kinase activation, and cyclic AMP accumulation. After a 2-h incubatin, the results showed that the dose required to elicit a minimal significant stimulation of steroidogenesis was 0.01 microng/ml LH. At this and higher concentrations of LH, a concomitant stimulation of protein kinase activity and progesterone synthesis was also consistently observed. However, significant accumulation of cyclic AMP became consistently detectable only at 0.1 microng/ml LH. This report is the first to show a positive correlation between the activation of cyclic AMP-dependent protein kinase and the stimulation of steroidogenesis in the corpus luteum at the same minimal effective level of LH. These results indicate that cyclic AMP and the cyclic AMP-dependent protein kinase probably play important intermediary roles in the stimulation of steroidogenesis by LH in the bovine corpus luteum.", "contents": "Reevaluation of the role of cyclic adenosine 3',5'-monophosphate and protein kinase in the stimulation of steroidogenesis by luteinizing hormone in bovine corpus luteum slices. Incubation of bovine corpus luteum slices at 37 C with luteinizing hormone showed that 10.0 microng LH/ml caused a maximum rise in tissue cyclic AMP content within 15 min. Slices incubated with 1.0 or 0.1 microng LH/ml showed a much more gradual accumulation of this nucleotide. In the absence of added LH, a marked decline in the amount of cyclic AMP was observed during the first 60 min. The possible role of cyclic AMP in the action of LH was reexamined by studying the dose-response effect of LH on the stimulation of progesterone synthesis, cyclic AMP-dependent protein kinase activation, and cyclic AMP accumulation. After a 2-h incubatin, the results showed that the dose required to elicit a minimal significant stimulation of steroidogenesis was 0.01 microng/ml LH. At this and higher concentrations of LH, a concomitant stimulation of protein kinase activity and progesterone synthesis was also consistently observed. However, significant accumulation of cyclic AMP became consistently detectable only at 0.1 microng/ml LH. This report is the first to show a positive correlation between the activation of cyclic AMP-dependent protein kinase and the stimulation of steroidogenesis in the corpus luteum at the same minimal effective level of LH. These results indicate that cyclic AMP and the cyclic AMP-dependent protein kinase probably play important intermediary roles in the stimulation of steroidogenesis by LH in the bovine corpus luteum."}
{"id": "PMID:192541", "title": "Perchlorate ion enhances mouse thyroid responsiveness to thyrotropin, human chorionic gonadotropin and long acting thyroid stimulator.", "content": "Perchlorate treatment of mice increased by 1.5-2-fold the thyroid secretory response to TSH, hCG and LATS, in the McKenzie bioassay. Perchlorate alone did not increase basal plasma radioactivity. Perchlorate augmentation of the secretory response index was roughly proportional to the level of stimulation; it was similar for all three stimulators despite their different time courses of action which were unaltered by perchlorate; it was the same whether perchlorate administration preceded, coincided with or shortly followed injection of the stimulator, a finding in keeping with the slow clearance of this ion. The perchlorate effect was dose-related, although within a narrow range (6.25-12.5 microng/mouse). Near-maximal per chlorate effect was obtained with a dose (12.5 microng) which, when tested in different experimental conditions (MMI-blocked thyroid), discharged 80% of intrathyroidal radioiodide. Perchlorate exerted its augmenting effect by enhancing thyroid secretion: it increased plasma radioiodothyronines and radioiodide concentrations without decreaseing the blood disappearance rates of iodide and iodothyronines. The potentiating effect of perchlorate probably takes place at a step prior to cyclic AMP action since it did not affect dbcAMP-stimulated secretion. The perchlorate effect may be indirect, through mobilization of minute amounts of intrathyroidal iodide.", "contents": "Perchlorate ion enhances mouse thyroid responsiveness to thyrotropin, human chorionic gonadotropin and long acting thyroid stimulator. Perchlorate treatment of mice increased by 1.5-2-fold the thyroid secretory response to TSH, hCG and LATS, in the McKenzie bioassay. Perchlorate alone did not increase basal plasma radioactivity. Perchlorate augmentation of the secretory response index was roughly proportional to the level of stimulation; it was similar for all three stimulators despite their different time courses of action which were unaltered by perchlorate; it was the same whether perchlorate administration preceded, coincided with or shortly followed injection of the stimulator, a finding in keeping with the slow clearance of this ion. The perchlorate effect was dose-related, although within a narrow range (6.25-12.5 microng/mouse). Near-maximal per chlorate effect was obtained with a dose (12.5 microng) which, when tested in different experimental conditions (MMI-blocked thyroid), discharged 80% of intrathyroidal radioiodide. Perchlorate exerted its augmenting effect by enhancing thyroid secretion: it increased plasma radioiodothyronines and radioiodide concentrations without decreaseing the blood disappearance rates of iodide and iodothyronines. The potentiating effect of perchlorate probably takes place at a step prior to cyclic AMP action since it did not affect dbcAMP-stimulated secretion. The perchlorate effect may be indirect, through mobilization of minute amounts of intrathyroidal iodide."}
{"id": "PMID:192542", "title": "Female steroid hormones and lipoprotein synthesis in the cockerel: effects of progesterone and nafoxidine on the estrogenic stimulation of very low density lipoproteins (VLDL) synthesis.", "content": "Since progesterone is known to modulate the effects of estradiol in a number of organ systems, we have studied the effects of the two hormones on very low density lipoproteins (VLDL) synthesis in the cockerel. We have also examined the effect of an estrogen antagonist, nafoxidine-HCl, on the process. When three week-old cockerels were treated with a single injection of estradiol (1 mg) or estradiol (1 mg) + progesterone (2 mg), plasma VLDL increased within 5 h, reached a peak at 48 h and returned to baseline values at 68 h. There was no significant difference between estradiol or estradiol + progesterone treated animals. Liver slices were prepared from similarly treated animals and incubated in vitro with L-[3H]lysine for 2 h. Following homogenization and centrifugation at 105,000 X g, newly synthesized VLDL were quantitiated in the supernatant fluid by immunoprecipitation with a monospecific antibody. Radioactivity incorporated into VLDL was found to increase from low baseline levels to a peak at about 17 h after treatment. There was, again, no significant difference between estradiol and estradiol + progesterone-treated animals. Estrogen priming or progesterone pretreatment also did not significantly alter the VLDL biosynthetic response in liver slices to estradiol alone or in combination with progesterone. When the estrogen-antagonist nafoxidine-HCl (5 mg) was administered simultaneously with estradiol (1 mg), it totally inhibited the VLDL biosynthetic response in liver slices in vitro. The interaction of estradio, progesterone and nafoxidine-HCl on the hepatic synthesis of VLDL should serve as a valuable model for the study of VLDL synthesis and its regulation as well as the mode of action of the sex steroid hormones in the liver.", "contents": "Female steroid hormones and lipoprotein synthesis in the cockerel: effects of progesterone and nafoxidine on the estrogenic stimulation of very low density lipoproteins (VLDL) synthesis. Since progesterone is known to modulate the effects of estradiol in a number of organ systems, we have studied the effects of the two hormones on very low density lipoproteins (VLDL) synthesis in the cockerel. We have also examined the effect of an estrogen antagonist, nafoxidine-HCl, on the process. When three week-old cockerels were treated with a single injection of estradiol (1 mg) or estradiol (1 mg) + progesterone (2 mg), plasma VLDL increased within 5 h, reached a peak at 48 h and returned to baseline values at 68 h. There was no significant difference between estradiol or estradiol + progesterone treated animals. Liver slices were prepared from similarly treated animals and incubated in vitro with L-[3H]lysine for 2 h. Following homogenization and centrifugation at 105,000 X g, newly synthesized VLDL were quantitiated in the supernatant fluid by immunoprecipitation with a monospecific antibody. Radioactivity incorporated into VLDL was found to increase from low baseline levels to a peak at about 17 h after treatment. There was, again, no significant difference between estradiol and estradiol + progesterone-treated animals. Estrogen priming or progesterone pretreatment also did not significantly alter the VLDL biosynthetic response in liver slices to estradiol alone or in combination with progesterone. When the estrogen-antagonist nafoxidine-HCl (5 mg) was administered simultaneously with estradiol (1 mg), it totally inhibited the VLDL biosynthetic response in liver slices in vitro. The interaction of estradio, progesterone and nafoxidine-HCl on the hepatic synthesis of VLDL should serve as a valuable model for the study of VLDL synthesis and its regulation as well as the mode of action of the sex steroid hormones in the liver."}
{"id": "PMID:192543", "title": "Relationship of biochemical and morphological changes in rat thyroid and proton spin-relaxation of the tissue water.", "content": "The effect was studied of biochemical and morphological changes induced by antithyroid substances (PTU, C10(-4)) on proton spin-relaxation properties of rat thyroid gland. It was found that thyroid stimulated by PTU (0.05%) or C10(-4) (1.0%) exhibit marked morphological changes (hyperplasia and epithelial hypertrophy) with alteration of the soluble iodoprotein pattern (content and composition.). Both relaxation times spin-lattice (T1) and spin-spin (T2) were increasing with the lenght of treatment with antithyroid drugs. Reversibility of the process was noted in accordance with biochemical and morphological data. The relaxation rate (formula: see text) for thyroid tissue water was in positive correlation with the suluble protein concentration and particularly with the TG content in the gland. There was no difference in relaxation times between normal thyroid and gland of rats treated chronically with excess iodide. The observed difference in T1 between normal glands and glands of PTU,-C10(-4)--treated rats was comparable with that found in cases of human thyroid cancer. This finding is of importance when the diagnostic potential of NMR in the detection of malignancy is considered. In conclusion, a strong correlation was found between microstructural and biochemical changes of the thyroid gland and proton magnetic relaxation of tissue water. The striking difference between the proton spin-relaxation times in normal and in goiter thyroid glands of rats suggests that pulsed NMR spectroscopy could be a method for evaluation of some disturbances in thyroid gland.", "contents": "Relationship of biochemical and morphological changes in rat thyroid and proton spin-relaxation of the tissue water. The effect was studied of biochemical and morphological changes induced by antithyroid substances (PTU, C10(-4)) on proton spin-relaxation properties of rat thyroid gland. It was found that thyroid stimulated by PTU (0.05%) or C10(-4) (1.0%) exhibit marked morphological changes (hyperplasia and epithelial hypertrophy) with alteration of the soluble iodoprotein pattern (content and composition.). Both relaxation times spin-lattice (T1) and spin-spin (T2) were increasing with the lenght of treatment with antithyroid drugs. Reversibility of the process was noted in accordance with biochemical and morphological data. The relaxation rate (formula: see text) for thyroid tissue water was in positive correlation with the suluble protein concentration and particularly with the TG content in the gland. There was no difference in relaxation times between normal thyroid and gland of rats treated chronically with excess iodide. The observed difference in T1 between normal glands and glands of PTU,-C10(-4)--treated rats was comparable with that found in cases of human thyroid cancer. This finding is of importance when the diagnostic potential of NMR in the detection of malignancy is considered. In conclusion, a strong correlation was found between microstructural and biochemical changes of the thyroid gland and proton magnetic relaxation of tissue water. The striking difference between the proton spin-relaxation times in normal and in goiter thyroid glands of rats suggests that pulsed NMR spectroscopy could be a method for evaluation of some disturbances in thyroid gland."}
{"id": "PMID:192544", "title": "Fine structure of adrenal cortex in ectopic ACTH syndrome.", "content": "A 49-year-old man with pancreatic adenocarcinoma, suggestive of islet cell origin, showed clinical and biochemical features of ectopic ACTH syndrome and underwent bilateral adrenalectomy. Light microscopy revealed adrenocortical compact cell hyperplasia and lipid depletion. The zona glomerulosa was detected in small foci and fasciculata cells extended up to the capsule. Electron microscopy disclosed enlargement of adrenocortical cells, massive SER accumulation, RER increase, lipid depletion, prominence of the Golgi apparatus and development of complex interdigitations between closely apposed cell membranes. These changes were attributed to the stimulative effect of ACTH discharged from the non-pituitary tumor. Mitochondria exhibited enlargement, pleomorphism and cavitation. Most of the adrenocortical cells contained mitochondria with vesicular cristae--a characteristic feature of fasciculata cells. In a few cells, under the capsule, some mitochondria possessed lamellar cristae. Gradual transformation to the vesicular type was, however, apparent indicating that mitochondria are not rigidly constant structures.", "contents": "Fine structure of adrenal cortex in ectopic ACTH syndrome. A 49-year-old man with pancreatic adenocarcinoma, suggestive of islet cell origin, showed clinical and biochemical features of ectopic ACTH syndrome and underwent bilateral adrenalectomy. Light microscopy revealed adrenocortical compact cell hyperplasia and lipid depletion. The zona glomerulosa was detected in small foci and fasciculata cells extended up to the capsule. Electron microscopy disclosed enlargement of adrenocortical cells, massive SER accumulation, RER increase, lipid depletion, prominence of the Golgi apparatus and development of complex interdigitations between closely apposed cell membranes. These changes were attributed to the stimulative effect of ACTH discharged from the non-pituitary tumor. Mitochondria exhibited enlargement, pleomorphism and cavitation. Most of the adrenocortical cells contained mitochondria with vesicular cristae--a characteristic feature of fasciculata cells. In a few cells, under the capsule, some mitochondria possessed lamellar cristae. Gradual transformation to the vesicular type was, however, apparent indicating that mitochondria are not rigidly constant structures."}
{"id": "PMID:192545", "title": "Post-EEG seizure depression of human limbic neurons is not determined by their response to probable hypoxia.", "content": "A subclinical EEG seizure occurred in each of 2 patients during a test that repeatedly evoked probable mild cerebral hypoxia. The firing rate of the neurons was unaffected until the EEG seizure had been ongoing for over a minute. After the EEG seizures, all neurons were profoundly depressed regardless of whether their responses to hypoxia had been an increase, decrease, or no change in firing rate. These observations indicate that the mechanism responsible for post-EEG seizure depression of neuronal firing is probably not cerebral hypoxia.", "contents": "Post-EEG seizure depression of human limbic neurons is not determined by their response to probable hypoxia. A subclinical EEG seizure occurred in each of 2 patients during a test that repeatedly evoked probable mild cerebral hypoxia. The firing rate of the neurons was unaffected until the EEG seizure had been ongoing for over a minute. After the EEG seizures, all neurons were profoundly depressed regardless of whether their responses to hypoxia had been an increase, decrease, or no change in firing rate. These observations indicate that the mechanism responsible for post-EEG seizure depression of neuronal firing is probably not cerebral hypoxia."}
{"id": "PMID:192547", "title": "Prostaglandin E2 production in 3T3 cells transformed by polyoma virus raises the intracellular adenosine 3':5'-monophosphate levels.", "content": "High cellular adenosine 3':5'-monophosphate (cyclic AMP) were found in a polyoma-virus-transformed 3T3 fibroblast line, which produces comparatively high prostaglandin E2 concentrations. Prostaglandin E2 and cyclic AMP increased with time during 6 days of growth. Both effects were prevented by three different cyclo-oxygenase inhibitors. Addition of prostaglandin E2, at a concentration which would been synthesized in the absence of inhibitor, reversed the effect of indomethacin, one of the cyclo-oxygenase inhibitors, on cyclic AMP. It is concluded that endogenous prostaglandin E2 production in these transformed cells influences their cellular cyclic AMP levels.", "contents": "Prostaglandin E2 production in 3T3 cells transformed by polyoma virus raises the intracellular adenosine 3':5'-monophosphate levels. High cellular adenosine 3':5'-monophosphate (cyclic AMP) were found in a polyoma-virus-transformed 3T3 fibroblast line, which produces comparatively high prostaglandin E2 concentrations. Prostaglandin E2 and cyclic AMP increased with time during 6 days of growth. Both effects were prevented by three different cyclo-oxygenase inhibitors. Addition of prostaglandin E2, at a concentration which would been synthesized in the absence of inhibitor, reversed the effect of indomethacin, one of the cyclo-oxygenase inhibitors, on cyclic AMP. It is concluded that endogenous prostaglandin E2 production in these transformed cells influences their cellular cyclic AMP levels."}
{"id": "PMID:192548", "title": "Prostaglandin production by normal and transformed 3T3 fibroblasts in cell culture.", "content": "Prostaglandin E2 and prostaglandin F2alpha were quantitatively determined in culture media from Balb/c 3T3 fibroblasts and two virus-transformed derivatives of these cells. Regular and (simian virus 40)-transformed 3T3 cells produced low and almost identical prostaglandin E2 concentrations. The levels were maximal (10 ng/ml) 24 h after planting and decreased during the next 96 h to 2.5 ng/ml. In contrast, polyoma-virus-transformed 3T3 cells produced prostaglandin E2 continuously for 120 h, giving a final concentration of 270 ng/ml. Fresh medium supplemented with calf serum reinitiated prostaglandin production in confluent 3T3 cells. Maximal prostaglandin E2 concentrations were obtained between 6 and 18 h after medium change and were proportional to the serum concentration of the medium. Indomethacin (10(-6) M) completely inhibited prostaglandin E2 production but not prostaglandin F2alpha production by these cells.", "contents": "Prostaglandin production by normal and transformed 3T3 fibroblasts in cell culture. Prostaglandin E2 and prostaglandin F2alpha were quantitatively determined in culture media from Balb/c 3T3 fibroblasts and two virus-transformed derivatives of these cells. Regular and (simian virus 40)-transformed 3T3 cells produced low and almost identical prostaglandin E2 concentrations. The levels were maximal (10 ng/ml) 24 h after planting and decreased during the next 96 h to 2.5 ng/ml. In contrast, polyoma-virus-transformed 3T3 cells produced prostaglandin E2 continuously for 120 h, giving a final concentration of 270 ng/ml. Fresh medium supplemented with calf serum reinitiated prostaglandin production in confluent 3T3 cells. Maximal prostaglandin E2 concentrations were obtained between 6 and 18 h after medium change and were proportional to the serum concentration of the medium. Indomethacin (10(-6) M) completely inhibited prostaglandin E2 production but not prostaglandin F2alpha production by these cells."}
{"id": "PMID:192549", "title": "Phospholipid binding and self-association of the major apoprotein of human and baboon high-density lipoproteins.", "content": "The purpose of this study was to establish a relationship between self-association and phospholipid binding of the human and the baboon apoA-I protein. The enthalpy changes on binding dimyristoyl lecithin and lysolecithin to either the human or the baboon native apoA-I protein were measured in a microcalorimeter. An endothermal process, most pronounced for the human apoprotein, was observed at low phospholipid levels. At higher phospholipid to protein ratios the binding was exothermal. Gel filtration experiments on Sephadex G-200 showed that the native apoprotein of both species consists of dimers and tetramers. The baboon native apoA-I protein contained a higher amount of dimers. After preincubation of the apoA-I protein with lysolecithin, the enthalpy changes measured on subsequent binding of dimyristoyl lecithin were shifted towards more exothermal values compared to the curve for the native apoprotein. The amplitude of this shift corresponds to that of the endothermal process observed on binding dimyristoyl lecithin to the native apoprotein. This process was attributed to a phospholipid-induced disaggregation of the apoA-I protein. Gel filtration data showed a decreased extent of aggregation in the apoA-I protein preincubated with lysolecithin. This sample consisted exclusively of dimers. Ultracentrifugal flotation of the complexes formed between the apoA-I protein, and respectively dimyristoyl lecithin and sphingomyelin indicated that preincubation with lysolecithin increased the extent of complex formation. These results suggest that the dimeric form of the apoA-I protein possesses the highest affinity for phospholipids. Any dissociation of higher polymers enhances the phospholipid-binding capacity of the human and the baboon apoA-I protein.", "contents": "Phospholipid binding and self-association of the major apoprotein of human and baboon high-density lipoproteins. The purpose of this study was to establish a relationship between self-association and phospholipid binding of the human and the baboon apoA-I protein. The enthalpy changes on binding dimyristoyl lecithin and lysolecithin to either the human or the baboon native apoA-I protein were measured in a microcalorimeter. An endothermal process, most pronounced for the human apoprotein, was observed at low phospholipid levels. At higher phospholipid to protein ratios the binding was exothermal. Gel filtration experiments on Sephadex G-200 showed that the native apoprotein of both species consists of dimers and tetramers. The baboon native apoA-I protein contained a higher amount of dimers. After preincubation of the apoA-I protein with lysolecithin, the enthalpy changes measured on subsequent binding of dimyristoyl lecithin were shifted towards more exothermal values compared to the curve for the native apoprotein. The amplitude of this shift corresponds to that of the endothermal process observed on binding dimyristoyl lecithin to the native apoprotein. This process was attributed to a phospholipid-induced disaggregation of the apoA-I protein. Gel filtration data showed a decreased extent of aggregation in the apoA-I protein preincubated with lysolecithin. This sample consisted exclusively of dimers. Ultracentrifugal flotation of the complexes formed between the apoA-I protein, and respectively dimyristoyl lecithin and sphingomyelin indicated that preincubation with lysolecithin increased the extent of complex formation. These results suggest that the dimeric form of the apoA-I protein possesses the highest affinity for phospholipids. Any dissociation of higher polymers enhances the phospholipid-binding capacity of the human and the baboon apoA-I protein."}
{"id": "PMID:192550", "title": "Thyrotropin binding to and adenylate cyclase activity of porcine thyroid plasma membranes.", "content": "Plasma membranes have been purified from porcine thyroid gland homogenate by discontinuous sucrose gradient centrifugation. The preparations contained specific binding sites for thyrotropin but not for luteinizing hormone or the beta subunits of thyrotropin and luteinizing hormone. Optimum conditions of 125I-labeled thyrotropin binding were pH 6.0-6.5 and 37 degrees C. Thyrotropin binding was reduced by divalent (Ca2+, Mg2+) and monovalent cations (Na+, K+, Li+), 50% inhibition being obtained at 10 mM and 50 mM respectively. Displacement curves of 125I-labeled bovine or porcine thyrotropin by the unlabeled hormone from three species was in the order of increasing concentrations (bovine greater than porcine greater than human) which is the order of decreasing biological activity of these hormone preparations in the assay in vivo in the mouse. The validity of the results was established by controlling that porcine membranes bound the native and the 125I-labeled hormones with equal affinity. A single type of high-affinity (Kd = 0.28 nM) binding sites was detected for bovine and porcine thyrotropins. In contrast, porcine plasma membranes bound human thyrotropin with a lower affinity (Kd = 70 nM). A good correlation was found at equilibrium and in the conditions of the cyclase assay, between receptor occupancy and adenylate cyclase activation for the three hormones.", "contents": "Thyrotropin binding to and adenylate cyclase activity of porcine thyroid plasma membranes. Plasma membranes have been purified from porcine thyroid gland homogenate by discontinuous sucrose gradient centrifugation. The preparations contained specific binding sites for thyrotropin but not for luteinizing hormone or the beta subunits of thyrotropin and luteinizing hormone. Optimum conditions of 125I-labeled thyrotropin binding were pH 6.0-6.5 and 37 degrees C. Thyrotropin binding was reduced by divalent (Ca2+, Mg2+) and monovalent cations (Na+, K+, Li+), 50% inhibition being obtained at 10 mM and 50 mM respectively. Displacement curves of 125I-labeled bovine or porcine thyrotropin by the unlabeled hormone from three species was in the order of increasing concentrations (bovine greater than porcine greater than human) which is the order of decreasing biological activity of these hormone preparations in the assay in vivo in the mouse. The validity of the results was established by controlling that porcine membranes bound the native and the 125I-labeled hormones with equal affinity. A single type of high-affinity (Kd = 0.28 nM) binding sites was detected for bovine and porcine thyrotropins. In contrast, porcine plasma membranes bound human thyrotropin with a lower affinity (Kd = 70 nM). A good correlation was found at equilibrium and in the conditions of the cyclase assay, between receptor occupancy and adenylate cyclase activation for the three hormones."}
{"id": "PMID:192551", "title": "UDP-apiose/UDP-xylose synthase. Subunit composition and binding studies.", "content": "The UDP-apiose/UDP-xylose synthase from cell suspension cultures of parsley has been purified 1400-fold by an improved method. The ratio of apiose to xylose formed from UDP-D-glucuronic acid (UDP-GlcUA) remained constant throughout the purification procedure. Dodecylsulfate-gel electrophoresis and sedimentation equilibrium measurements showed that this enzyme preparation is  composed of two proteins with molecular weights of 65000 and 86000. The two proteins which are present in a molar ratio of about 1:0.7 to 1:0.9 could not be separated by ammonium sulfate fractionation, chromatography on DEAE-cellulose at different pH-values, and on omega-aminoalkyl-Sepharose, and by gel filtration on Acrylex P-100. Each protein is composed of two apparently identical subunits. The presence of only two different subunits was confirmed by end group analysis in which glycine was found as N-terminal amino acid for the larger and lysine for the smaller protein. Crosslinking with dimethylsuberimidate gave dimers of the identical subunits but no hybrids. Separation of the two proteins was achieved on DEAE-cellulose in the presence of urea. After dialysis only the 86000-Mr protein showed enzyme activity with no significant change in the apiose/xylose ratio. However, in the absence of the 65000-Mr protein enzyme stability was decreased drastically. By equilibrium dialysis it was found that 0.5 mol UDP-GlcUA are bound per mole of 86000-Mr protein. NAD+ alone was not bound, but in the presence of UDP it was also bound in a ratio of 0.5 mol/mol catalytic protein. Experiments in which sodium borohydride was added to the enzyme incubation gave no indication that the 4-keto intermediate is bound as a Schiff base to the enzyme. Also no evidence for epimerization at C-3 of the 4-ulose intermediate prior to ring contraction to apiose was found.", "contents": "UDP-apiose/UDP-xylose synthase. Subunit composition and binding studies. The UDP-apiose/UDP-xylose synthase from cell suspension cultures of parsley has been purified 1400-fold by an improved method. The ratio of apiose to xylose formed from UDP-D-glucuronic acid (UDP-GlcUA) remained constant throughout the purification procedure. Dodecylsulfate-gel electrophoresis and sedimentation equilibrium measurements showed that this enzyme preparation is  composed of two proteins with molecular weights of 65000 and 86000. The two proteins which are present in a molar ratio of about 1:0.7 to 1:0.9 could not be separated by ammonium sulfate fractionation, chromatography on DEAE-cellulose at different pH-values, and on omega-aminoalkyl-Sepharose, and by gel filtration on Acrylex P-100. Each protein is composed of two apparently identical subunits. The presence of only two different subunits was confirmed by end group analysis in which glycine was found as N-terminal amino acid for the larger and lysine for the smaller protein. Crosslinking with dimethylsuberimidate gave dimers of the identical subunits but no hybrids. Separation of the two proteins was achieved on DEAE-cellulose in the presence of urea. After dialysis only the 86000-Mr protein showed enzyme activity with no significant change in the apiose/xylose ratio. However, in the absence of the 65000-Mr protein enzyme stability was decreased drastically. By equilibrium dialysis it was found that 0.5 mol UDP-GlcUA are bound per mole of 86000-Mr protein. NAD+ alone was not bound, but in the presence of UDP it was also bound in a ratio of 0.5 mol/mol catalytic protein. Experiments in which sodium borohydride was added to the enzyme incubation gave no indication that the 4-keto intermediate is bound as a Schiff base to the enzyme. Also no evidence for epimerization at C-3 of the 4-ulose intermediate prior to ring contraction to apiose was found."}
{"id": "PMID:192552", "title": "Determination of the solution conformation of adenosein 2':3'-monophosphate by nuclear magnetic resonance with lanthanide probes.", "content": "The aqueous solution conformation of adenosine 2':3'-monophosphate at pH 2.5 has been determined by a nuclear magnetic resonance method utilizing lanthanide ions as shift and relaxation probes. The ribose conformation is best described as a rapid equilibrium of 2'-endo(3'-exo) and 3'-endo(2'-exo) conformations in a ratio of approximately 2 to 1. The orientation of the base relative to ribose is restricted to a narrow range about chiCN=-70 degrees.", "contents": "Determination of the solution conformation of adenosein 2':3'-monophosphate by nuclear magnetic resonance with lanthanide probes. The aqueous solution conformation of adenosine 2':3'-monophosphate at pH 2.5 has been determined by a nuclear magnetic resonance method utilizing lanthanide ions as shift and relaxation probes. The ribose conformation is best described as a rapid equilibrium of 2'-endo(3'-exo) and 3'-endo(2'-exo) conformations in a ratio of approximately 2 to 1. The orientation of the base relative to ribose is restricted to a narrow range about chiCN=-70 degrees."}
{"id": "PMID:192553", "title": "Role of divalent ions in folding of tRNA.", "content": "The native structure of tRNA is not achieved in low salt (4.5 mM Na+, 25 degrees C), but can be restored by addition of divalent ions. We have explored the structure of the central region in Escherichia coli tRNAfMet by absorption and emission spectroscopy of 4-thiouracil, and the structure of the anticodon loop in yeast tRNAPhe by fluorescence of the 'Y' base, versus the number of manganese ions bound to tRNA, which was derived from electron spin resonance. The fluorescence of the reduced 8-13 photoproduct (in which 4-thiouracil at position 8 is crosslinked to cytosine at position 13) was also analysed. In low salt (e.g. 4.5 mM Na+), the region of 4-thiouracil is affected strongly as the first eight Mn2+ bind to tRNA, whereas the fluorescence of the 'Y' base is affected only after four Mn2+ are bound. Considering the structural similarities of the two tRNAs, this suggests that the reorganisation brought about by divalent ions starts in the central region, the anticodon loop being affected later. The binding of divalent ions to each region starts together with its restructuration. Monovalent ions can substitute for divalent ions in this process, a 15 mM sodium concentration being equivalent to the binding of the first five Mn2+. If divalent ions are then added, even the first ones distribute themselves between both the central and the anticodon region. Alternatively, the renaturation may be achieved by monovalent ions only, implying that no sites exist whose occupancy by divalent ions is crucial for the native structure. These observations suggest that the  role and means of divalent ion binding to tRNA are largely explainable in terms of a simple maganese-phosphate binding supplemented by electrostatic interaction with distant phosphates.", "contents": "Role of divalent ions in folding of tRNA. The native structure of tRNA is not achieved in low salt (4.5 mM Na+, 25 degrees C), but can be restored by addition of divalent ions. We have explored the structure of the central region in Escherichia coli tRNAfMet by absorption and emission spectroscopy of 4-thiouracil, and the structure of the anticodon loop in yeast tRNAPhe by fluorescence of the 'Y' base, versus the number of manganese ions bound to tRNA, which was derived from electron spin resonance. The fluorescence of the reduced 8-13 photoproduct (in which 4-thiouracil at position 8 is crosslinked to cytosine at position 13) was also analysed. In low salt (e.g. 4.5 mM Na+), the region of 4-thiouracil is affected strongly as the first eight Mn2+ bind to tRNA, whereas the fluorescence of the 'Y' base is affected only after four Mn2+ are bound. Considering the structural similarities of the two tRNAs, this suggests that the reorganisation brought about by divalent ions starts in the central region, the anticodon loop being affected later. The binding of divalent ions to each region starts together with its restructuration. Monovalent ions can substitute for divalent ions in this process, a 15 mM sodium concentration being equivalent to the binding of the first five Mn2+. If divalent ions are then added, even the first ones distribute themselves between both the central and the anticodon region. Alternatively, the renaturation may be achieved by monovalent ions only, implying that no sites exist whose occupancy by divalent ions is crucial for the native structure. These observations suggest that the  role and means of divalent ion binding to tRNA are largely explainable in terms of a simple maganese-phosphate binding supplemented by electrostatic interaction with distant phosphates."}
{"id": "PMID:192554", "title": "Stimulatory and inhibitory effects of dimethyl sulfoxide and ethylene glycol on ATPase activity and calcium transport of sarcoplasmic membranes.", "content": "1. The effect of dimethyl sulfoxide (Me2SO) and ethylene glycol on two different preparations of the sarcoplasmic reticulum, i.e. native membranes and membranes whose phospholipids were hydrolyzed by phospholipase A, were investigated using ATP and p-nitrophenylphosphate as substrates. 2. Me2SO and ethylene glycol inhibit both calcium-dependent ATP hydrolysis and ATP-supported calcium transport by native vesicles. 3. In contrast, calcium-dependent p-nitrophenylphosphatase activity as well as p-nitrophenyl-phosphate-supported calcium transport are activated by both agents at concentrations lower than 30% (v/v). 4. Me2SO strongly stimulates p-nitrophenylphosphate activity of vesicles treated with phospholipase A, but has relatively little effect on p-nitrophenylphosphatase activity of native vesicles. 5. Up to a concentration of approximately 40% Me2SO (v/v) the inhibiting effect on the calcium-dependent ATPase is fully reversible, but only partially reversible on calcium transport. 6. In the concentration range where Me2SO inhibits ATP hydrolysis and calcium transport, it does not affect ATP binding to the membranes nor calcium-dependent formation of phospho-protein. 7. The rate of dephosphorylation as well as the rate of Pi exchange between ATP and ADP are markedly reduced by the presence of 30% Me2SO (v/v). 8. While Me2SO inhibits passive calcium efflux, ethylene glycol produces a considerable activation. 9. ADP-dependent calcium efflux and ATP synthesis are activated by 15% Me2SO (v/v). Ethylene glycol reduces both activities. 10. The results suggest that the respective substrate-enzyme complexes are differently affected by the agents, resulting either in inhibition or stimulation", "contents": "Stimulatory and inhibitory effects of dimethyl sulfoxide and ethylene glycol on ATPase activity and calcium transport of sarcoplasmic membranes. 1. The effect of dimethyl sulfoxide (Me2SO) and ethylene glycol on two different preparations of the sarcoplasmic reticulum, i.e. native membranes and membranes whose phospholipids were hydrolyzed by phospholipase A, were investigated using ATP and p-nitrophenylphosphate as substrates. 2. Me2SO and ethylene glycol inhibit both calcium-dependent ATP hydrolysis and ATP-supported calcium transport by native vesicles. 3. In contrast, calcium-dependent p-nitrophenylphosphatase activity as well as p-nitrophenyl-phosphate-supported calcium transport are activated by both agents at concentrations lower than 30% (v/v). 4. Me2SO strongly stimulates p-nitrophenylphosphate activity of vesicles treated with phospholipase A, but has relatively little effect on p-nitrophenylphosphatase activity of native vesicles. 5. Up to a concentration of approximately 40% Me2SO (v/v) the inhibiting effect on the calcium-dependent ATPase is fully reversible, but only partially reversible on calcium transport. 6. In the concentration range where Me2SO inhibits ATP hydrolysis and calcium transport, it does not affect ATP binding to the membranes nor calcium-dependent formation of phospho-protein. 7. The rate of dephosphorylation as well as the rate of Pi exchange between ATP and ADP are markedly reduced by the presence of 30% Me2SO (v/v). 8. While Me2SO inhibits passive calcium efflux, ethylene glycol produces a considerable activation. 9. ADP-dependent calcium efflux and ATP synthesis are activated by 15% Me2SO (v/v). Ethylene glycol reduces both activities. 10. The results suggest that the respective substrate-enzyme complexes are differently affected by the agents, resulting either in inhibition or stimulation"}
{"id": "PMID:192555", "title": "Juvenile familial hypertriglyceridemia and growth retardation. Clinical and biochemical observations in three siblings.", "content": "Familial hypertriglyceridemia or hyperlipoproteinemia type I was detected in three siblings aged 6, 11, and 14 of an otherwise normal Turkish family of 10 members. Initial values ranged from 1780 to 3750 mg/100 ml triglycerides in the milky white serum; cholesterol was normal. Lipoprotein pattern on agarose and acrylamide gel revealed a heavy band of chylomicrons and missing HDL; post-heparin lipolytic activity was decreased to about 30% of normal. Chylomicronemia could be induced by a fat-rich (50% of total calories) diet, but not by carbohydrates. On a low fat diet (5%) during hospitalization chylomicrons disappeared, and triglycerides decreased to about 450 mg/100 ml. Phenocopies of hypertriglyceridemia could be excluded. All three patients were the only members of the family who were small, below the third percentile. Their bone age was retarded from 18 to 30 months. There was no indication for an endocrine cause of the growth retardation: four different stimulation tests revealed normal growth hormone response, thyroid and adrenal functions were not impaired; sexual development was normal. Increased glucose assimilation was observed during intravenous and oral glucose load. Peak serum insulin response was above normal during stimulation tests. The possible etiologic role of hypertriglyceridemia in this concomitant growth retardation is discussed.", "contents": "Juvenile familial hypertriglyceridemia and growth retardation. Clinical and biochemical observations in three siblings. Familial hypertriglyceridemia or hyperlipoproteinemia type I was detected in three siblings aged 6, 11, and 14 of an otherwise normal Turkish family of 10 members. Initial values ranged from 1780 to 3750 mg/100 ml triglycerides in the milky white serum; cholesterol was normal. Lipoprotein pattern on agarose and acrylamide gel revealed a heavy band of chylomicrons and missing HDL; post-heparin lipolytic activity was decreased to about 30% of normal. Chylomicronemia could be induced by a fat-rich (50% of total calories) diet, but not by carbohydrates. On a low fat diet (5%) during hospitalization chylomicrons disappeared, and triglycerides decreased to about 450 mg/100 ml. Phenocopies of hypertriglyceridemia could be excluded. All three patients were the only members of the family who were small, below the third percentile. Their bone age was retarded from 18 to 30 months. There was no indication for an endocrine cause of the growth retardation: four different stimulation tests revealed normal growth hormone response, thyroid and adrenal functions were not impaired; sexual development was normal. Increased glucose assimilation was observed during intravenous and oral glucose load. Peak serum insulin response was above normal during stimulation tests. The possible etiologic role of hypertriglyceridemia in this concomitant growth retardation is discussed."}
{"id": "PMID:192556", "title": "Gamma-aminobutyric acid (GABA) and sleep. The influence of di-n-propylacetic acid on sleep in man.", "content": "The effects of di-n-propylacetic acid (DPA) on sleep, for some years used as an anticonvulsive drug, has been investigated in 11 healthy volunteers using all-night sleep EEG recordings. DPA acts by an enhancement of the gamma-aminobutyric acid (GABA) level of the brain. Its influence on sleep seemed to be of interest on account of the metabolic relationship of GABA to other short chain fatty acids. After short-term application only a shortening of the time to fall asleep and of the waking time could be found, whereas under long-term administration a decrease in deep synchronous sleep could be observed. In contrast to the results known from animal studies no marked influence on REM sleep was observed. The action of DPA on sleep is similar to that of diphenylhydantoin. No so-called matitudinal 'hangover' could be revelaed in either drug;", "contents": "Gamma-aminobutyric acid (GABA) and sleep. The influence of di-n-propylacetic acid on sleep in man. The effects of di-n-propylacetic acid (DPA) on sleep, for some years used as an anticonvulsive drug, has been investigated in 11 healthy volunteers using all-night sleep EEG recordings. DPA acts by an enhancement of the gamma-aminobutyric acid (GABA) level of the brain. Its influence on sleep seemed to be of interest on account of the metabolic relationship of GABA to other short chain fatty acids. After short-term application only a shortening of the time to fall asleep and of the waking time could be found, whereas under long-term administration a decrease in deep synchronous sleep could be observed. In contrast to the results known from animal studies no marked influence on REM sleep was observed. The action of DPA on sleep is similar to that of diphenylhydantoin. No so-called matitudinal 'hangover' could be revelaed in either drug;"}
{"id": "PMID:192560", "title": "Controlled clinical investigation of trimeprazine as a sleep-inducer in normal subjects.", "content": "The effects of acute introduction and withdrawal of trimeprazine (Vallergan), an antihistaminic phenothiazine derivative with known sedative effects, were investigated by a single blind polygraphic study in 8 healthy volunteers. A baseline placebo was given on Nights 1-3, followed either by 10 mg or 20 mg of the drug on Nights 4-6, and then withdrawal effects were recorded on Nights 7-9. The subjective effects of the drug and EEG sleep variables were determined on these nights. The results showed that the drug might have had dose related effects. REM-sleep was increased by 10 mg doses, which also caused an increase in SW sleep. There was no significant change after the 20 mg dose. Significant REM rebound was not observed after withdrawal of either dose. These characteristics may be of value in the treatment of certain aspects of sleep disturbances.", "contents": "Controlled clinical investigation of trimeprazine as a sleep-inducer in normal subjects. The effects of acute introduction and withdrawal of trimeprazine (Vallergan), an antihistaminic phenothiazine derivative with known sedative effects, were investigated by a single blind polygraphic study in 8 healthy volunteers. A baseline placebo was given on Nights 1-3, followed either by 10 mg or 20 mg of the drug on Nights 4-6, and then withdrawal effects were recorded on Nights 7-9. The subjective effects of the drug and EEG sleep variables were determined on these nights. The results showed that the drug might have had dose related effects. REM-sleep was increased by 10 mg doses, which also caused an increase in SW sleep. There was no significant change after the 20 mg dose. Significant REM rebound was not observed after withdrawal of either dose. These characteristics may be of value in the treatment of certain aspects of sleep disturbances."}
{"id": "PMID:192561", "title": "Effects of several catecholamines on sympathetic transmission to the myocardium: role of presynaptic alpha-adrenoceptors.", "content": "Effects of several alpha-adrenoceptor agonists on presynaptic alpha-adrenoceptors were evaluated by studying chronotropic responses to cardioaccelerator nerve stimulation in anesthetized dogs. I.v. infusions of norepinephrine (NE), methylnorepinephrine (MNE), epinephrine (E) or phenylephrine (PHE) in desipramine-treated dogs caused significant attenuation of nerve stimulation responses. The inhibitory influence of all these agents could be prevented by prior treatment with phentolamine, but not with haloperidol. Comparisons of relative pressor and presynaptic inhibitory actions of these compounds revealed that in equipressor doses, MNE caused a significantly greater attenuation of nerve stimmulation responses than NE, while PHE had similar pressor and presynaptic inhibitory activity to that of NE. The inhibition of chronotropic responses to nerve stimulation observed following E was significantly greater compared to its relative pressor effect. These results demonstrate the existence of a presynaptic alpha-adrenoceptor mechanism modulating cardiac rate in intact dogs and indicate that the false transmitter MNE may be more potent than NE in imparing neuronal transmission by an action on presynaptic alpha-adrenoceptors.", "contents": "Effects of several catecholamines on sympathetic transmission to the myocardium: role of presynaptic alpha-adrenoceptors. Effects of several alpha-adrenoceptor agonists on presynaptic alpha-adrenoceptors were evaluated by studying chronotropic responses to cardioaccelerator nerve stimulation in anesthetized dogs. I.v. infusions of norepinephrine (NE), methylnorepinephrine (MNE), epinephrine (E) or phenylephrine (PHE) in desipramine-treated dogs caused significant attenuation of nerve stimulation responses. The inhibitory influence of all these agents could be prevented by prior treatment with phentolamine, but not with haloperidol. Comparisons of relative pressor and presynaptic inhibitory actions of these compounds revealed that in equipressor doses, MNE caused a significantly greater attenuation of nerve stimmulation responses than NE, while PHE had similar pressor and presynaptic inhibitory activity to that of NE. The inhibition of chronotropic responses to nerve stimulation observed following E was significantly greater compared to its relative pressor effect. These results demonstrate the existence of a presynaptic alpha-adrenoceptor mechanism modulating cardiac rate in intact dogs and indicate that the false transmitter MNE may be more potent than NE in imparing neuronal transmission by an action on presynaptic alpha-adrenoceptors."}
{"id": "PMID:192562", "title": "Dopamine receptors in the femoral vascular bed of the dog as mediators of a vasodilator and sympathoinhibitory effect.", "content": "ET 495 and apomorphine, injected in small doses (0.1--1 microng/kg) into the femoral artery, induced a dose-dependent increase in femoral blood flow. This dilator effect was abolished by section of the ipsilateral femoral nerve and sciatic nerve, transection of the spinal cord, alpha-adrenoceptor blockade, ganglionic blockade and guanethidine. In addition, the increase in blood flow was inhibited by intravenous administration of haloperiol (2 mg/kg i.v.) or pimozide (2 mg/kg i.v.) and by injection of small doses (10--50 microng/kg) of these drugs into the femoral artery. It was concluded that a dopaminergic component located in the femoral vascular bed of the dog may be involved in the local vasodilator and sympathoinhibitory effect of apomorphine and ET 495.", "contents": "Dopamine receptors in the femoral vascular bed of the dog as mediators of a vasodilator and sympathoinhibitory effect. ET 495 and apomorphine, injected in small doses (0.1--1 microng/kg) into the femoral artery, induced a dose-dependent increase in femoral blood flow. This dilator effect was abolished by section of the ipsilateral femoral nerve and sciatic nerve, transection of the spinal cord, alpha-adrenoceptor blockade, ganglionic blockade and guanethidine. In addition, the increase in blood flow was inhibited by intravenous administration of haloperiol (2 mg/kg i.v.) or pimozide (2 mg/kg i.v.) and by injection of small doses (10--50 microng/kg) of these drugs into the femoral artery. It was concluded that a dopaminergic component located in the femoral vascular bed of the dog may be involved in the local vasodilator and sympathoinhibitory effect of apomorphine and ET 495."}
{"id": "PMID:192563", "title": "The mechanism of action of nicotine on vascular adrenergic neuroeffector transmission.", "content": "The aim of this study was to determine the site and mechanism of action of nicotine on sympathetic neuroeffector transmission in the isolated pulmonary artery of the rabbit. Nicotine and cocaine potentiated the constrictor response elicited by electrical-field stimulation of postganglionic adrenergic neurones. The potentiation was reversible and in the case of nicotine, no tachyphylaxis developed. The nicotine-induced potentiation was characterized by a rapid onset and an initial, transitory peak, while the enhancement caused by cocaine progressed more slowly and was monophasic. Hexamethonium and (+)-tubocurarine prevented the potentiation caused by nicotine. Nicotine did not prevent the adrenergic neurone blocking effect of bretylium on the response to field stimulation. Nicotine increased the stimulation-induced outflow of tritium from pulmonary artery preloaded with 3H-(--)-noradrenaline. Contractions of the artery elicited by tyramine were enhanced by pargyline, unaltered by nicotine and blocked by cocaine. Nicotine did not alter the concentration--response curve of exogenous (--)-noradrenaline while cocaine moved it to the left. The accumulation of 3H-(--)-noradrenaline by rabbit isolated aorta was not altered by nicotine, hexamethonium and (+)-tubocurarine. The accumulation of 3H-nicotine by the aorta was much lower than that seen with 3H-(--)-noradrenaline. The disposition of the 3H-nicotine accumulation into adventitia and media was concentration-independent. These results suggest (1) that nicotine potentiates the neurogenic vasoconstriction response in part by increasing the stimulation-induced release of transmitter from adrenergic neurone terminals; (2) that the site of the nicotinic receptors mediating this action is located on the outer surface of the neurones; and (3) that the potentiation is not due to blockade of noradrenaline re-uptake.", "contents": "The mechanism of action of nicotine on vascular adrenergic neuroeffector transmission. The aim of this study was to determine the site and mechanism of action of nicotine on sympathetic neuroeffector transmission in the isolated pulmonary artery of the rabbit. Nicotine and cocaine potentiated the constrictor response elicited by electrical-field stimulation of postganglionic adrenergic neurones. The potentiation was reversible and in the case of nicotine, no tachyphylaxis developed. The nicotine-induced potentiation was characterized by a rapid onset and an initial, transitory peak, while the enhancement caused by cocaine progressed more slowly and was monophasic. Hexamethonium and (+)-tubocurarine prevented the potentiation caused by nicotine. Nicotine did not prevent the adrenergic neurone blocking effect of bretylium on the response to field stimulation. Nicotine increased the stimulation-induced outflow of tritium from pulmonary artery preloaded with 3H-(--)-noradrenaline. Contractions of the artery elicited by tyramine were enhanced by pargyline, unaltered by nicotine and blocked by cocaine. Nicotine did not alter the concentration--response curve of exogenous (--)-noradrenaline while cocaine moved it to the left. The accumulation of 3H-(--)-noradrenaline by rabbit isolated aorta was not altered by nicotine, hexamethonium and (+)-tubocurarine. The accumulation of 3H-nicotine by the aorta was much lower than that seen with 3H-(--)-noradrenaline. The disposition of the 3H-nicotine accumulation into adventitia and media was concentration-independent. These results suggest (1) that nicotine potentiates the neurogenic vasoconstriction response in part by increasing the stimulation-induced release of transmitter from adrenergic neurone terminals; (2) that the site of the nicotinic receptors mediating this action is located on the outer surface of the neurones; and (3) that the potentiation is not due to blockade of noradrenaline re-uptake."}
{"id": "PMID:192564", "title": "The inhibitory effect of cadmium on neuromuscular transmission in the rat.", "content": "Cadmium (0.125-1 mM) was found to inhibit the isometric response of the isolated rat hemidiaphragm during indirect stimulation, but not during direct stimulation. This effect of cadmium (1 mM) was completely reversed by ethyleneglycol bis-(aminoethyl)-N,N,N',N'-tetra-acetic acid (2 mM) or by L-cysteine (2 mM) but only partially by increased calcium. Cadmium (10 micronM) significantly reduced the quantal release of transmitter in the isolated phrenic diaphragm and a concentration of 0.1 mM frequently caused a complete failure of the endplate response after 30 min. The effect of cadmium on neuromuscular transmission could not be readily reversed by washing with cadmium-free solution. Miniature endplate potential frequency and amplitude were not significantly affected by cadmium (0.1 or 0.5 mM). The results suggest that the effect of cadmium on the isolated phrenic nerve-diaphragm is due largely to inhibition of calcium function at presynaptic nerve terminals.", "contents": "The inhibitory effect of cadmium on neuromuscular transmission in the rat. Cadmium (0.125-1 mM) was found to inhibit the isometric response of the isolated rat hemidiaphragm during indirect stimulation, but not during direct stimulation. This effect of cadmium (1 mM) was completely reversed by ethyleneglycol bis-(aminoethyl)-N,N,N',N'-tetra-acetic acid (2 mM) or by L-cysteine (2 mM) but only partially by increased calcium. Cadmium (10 micronM) significantly reduced the quantal release of transmitter in the isolated phrenic diaphragm and a concentration of 0.1 mM frequently caused a complete failure of the endplate response after 30 min. The effect of cadmium on neuromuscular transmission could not be readily reversed by washing with cadmium-free solution. Miniature endplate potential frequency and amplitude were not significantly affected by cadmium (0.1 or 0.5 mM). The results suggest that the effect of cadmium on the isolated phrenic nerve-diaphragm is due largely to inhibition of calcium function at presynaptic nerve terminals."}
{"id": "PMID:192572", "title": "Potentiation by crude kallikrein of the myotropic effect of angiotensin I in the isolated rabbit aortic strip.", "content": "Crude kallikrein (Padutin), but not pure kallikrein, when preincubated with angiotensin I caused a potentiation of the myotropic effect of decapeptide on the isolated continuously superfused rabbit aortic strip. Addition of converting enzyme inhibitor, SQ 20881, to the medium inhibited this potentiation. The potentiation by crude kallikrein of the myotropic effect of angiotensin I is probably due to the conversion of decapeptide to octapeptide angiotensin II. This study indicates that Padutin is not a pure kallikrein preparation and probably contains a kininase fraction which causes the conversion of angiotensin I.", "contents": "Potentiation by crude kallikrein of the myotropic effect of angiotensin I in the isolated rabbit aortic strip. Crude kallikrein (Padutin), but not pure kallikrein, when preincubated with angiotensin I caused a potentiation of the myotropic effect of decapeptide on the isolated continuously superfused rabbit aortic strip. Addition of converting enzyme inhibitor, SQ 20881, to the medium inhibited this potentiation. The potentiation by crude kallikrein of the myotropic effect of angiotensin I is probably due to the conversion of decapeptide to octapeptide angiotensin II. This study indicates that Padutin is not a pure kallikrein preparation and probably contains a kininase fraction which causes the conversion of angiotensin I."}
{"id": "PMID:192573", "title": "The effect of levamisole on phosphodiesterase activity.", "content": "Phosphodiesterase activity of mouse liver homogenates was estimated in presence and absence of levamisole. The enzyme activity was 1394 and 1399 nmoles/mg protein/30 min respectively. Our data show that levamisole does not affect the phosphodiesterase activity.", "contents": "The effect of levamisole on phosphodiesterase activity. Phosphodiesterase activity of mouse liver homogenates was estimated in presence and absence of levamisole. The enzyme activity was 1394 and 1399 nmoles/mg protein/30 min respectively. Our data show that levamisole does not affect the phosphodiesterase activity."}
{"id": "PMID:192574", "title": "Dexamethasone suppression of ovulation in PMS-treated immature rats.", "content": "A single injection of 2.0 mg/kg dexamethasone (DXM) administered at 51 h after pregnant mare serum gonadatropin (PMS) treatment inhibited both ovulation and luteinization. S.c. injection of human chorionic gonadotropin (HGG) caused ovulation and luteinization in DXM-PMS-treated rats, whereas treatment with ACTH failed to overcome the DXM inhibitory effect. These findings are interpreted to indicate that DXM inhibits ovulation through a mechanism which might involve the central nervous system.", "contents": "Dexamethasone suppression of ovulation in PMS-treated immature rats. A single injection of 2.0 mg/kg dexamethasone (DXM) administered at 51 h after pregnant mare serum gonadatropin (PMS) treatment inhibited both ovulation and luteinization. S.c. injection of human chorionic gonadotropin (HGG) caused ovulation and luteinization in DXM-PMS-treated rats, whereas treatment with ACTH failed to overcome the DXM inhibitory effect. These findings are interpreted to indicate that DXM inhibits ovulation through a mechanism which might involve the central nervous system."}
{"id": "PMID:192582", "title": "[Antiviral agents. XIX. Amantadine derivatives and several others].", "content": "The synthesis and pharmacological activity of several adamantane derivatives and analogs of tilorone are described as part of a systematic research on potential antiviral compounds and/or interferon inducers.", "contents": "[Antiviral agents. XIX. Amantadine derivatives and several others]. The synthesis and pharmacological activity of several adamantane derivatives and analogs of tilorone are described as part of a systematic research on potential antiviral compounds and/or interferon inducers."}
{"id": "PMID:192600", "title": "Evolution of neurohypophyseal hormones and their receptors.", "content": "Nine active neurohypophyseal principles have been isolated and identified among the vertebrates. Arginine-vasotocin is the most ubiquitous, occurring in pituitary glands from representatives of all the major vertebrate groups. There is much more variation in structure among the principles that resemble oxytocin. The manner in which these evolved remains unclear. Arginine-vasotocin stimulates smooth muscles from a wide variety of vertebrate species. It can stimulate contraction of oviducts from many jawed fishes and tetrapods. The oxytocin-like peptides are usually less active in this respect. Among adult mammals arginine-vasotocin is replaced by arginine-vasopressin which has much less oxytocin activity. Thus, although arginine-vasotocin may both stimulate oviducts and cause water retention in nonmammalian tetrapods, oxytocic and antidiuretic functions can be regulated independently by oxytocin and vasopressin in mammals. Arginine-vasotocin elicits vasoconstrictor responses in even the most primitive vertebrates. These may be systemic or regional. Their distribution may determine whether arginine-vasotocin acts as a diuretic or an antidiuretic agent. It is possible that the most primitive neurohypophyseal functions were related to cardiovascular regulation and that the neurohypophysis acquired its osmoregulatory functions later in vertebrate evolution.", "contents": "Evolution of neurohypophyseal hormones and their receptors. Nine active neurohypophyseal principles have been isolated and identified among the vertebrates. Arginine-vasotocin is the most ubiquitous, occurring in pituitary glands from representatives of all the major vertebrate groups. There is much more variation in structure among the principles that resemble oxytocin. The manner in which these evolved remains unclear. Arginine-vasotocin stimulates smooth muscles from a wide variety of vertebrate species. It can stimulate contraction of oviducts from many jawed fishes and tetrapods. The oxytocin-like peptides are usually less active in this respect. Among adult mammals arginine-vasotocin is replaced by arginine-vasopressin which has much less oxytocin activity. Thus, although arginine-vasotocin may both stimulate oviducts and cause water retention in nonmammalian tetrapods, oxytocic and antidiuretic functions can be regulated independently by oxytocin and vasopressin in mammals. Arginine-vasotocin elicits vasoconstrictor responses in even the most primitive vertebrates. These may be systemic or regional. Their distribution may determine whether arginine-vasotocin acts as a diuretic or an antidiuretic agent. It is possible that the most primitive neurohypophyseal functions were related to cardiovascular regulation and that the neurohypophysis acquired its osmoregulatory functions later in vertebrate evolution."}
{"id": "PMID:192601", "title": "Characterization of oxytocin receptors in the uterus and mammary gland.", "content": "High affinity binding sites for 3[H] oxytocin have been demonstrated in particulate fractions from rat uterus and oviduct, myometrium from the sow, ewe and human, ewe endometrium, and mammary gland from the lactating rat. The binding activity has been localized to enriched plasma membrane fractions from the rat uterus and mammary gland; cells isolated from the mammary gland also bind oxytocin. The apparent dissociation constant (Kd) for the interaction of oxytocin with its binding sites in a variety of tissue preparations is in the nanomolar range. The concentration of oxytocin eliciting half-maximal contraction of the rat isolated uterus corresponds to the apparent Kd of oxytocin interaction with uterine particulate fractions. Binding is specific with respect to the target tissue or cell, as well as to the ligand. The affinity of binding sites for oxytocin analogues corresponds generally to their potencies as agonists or antagonists. Factors that affect the binding of oxytocin affect the biological response in the same way. For example, certain divalent metal ions, which increase oxytocin binding activity, enhance the sensitivity of the contractile response of the uterus and mammary gland to oxytocin. Estrogen administration, which increases the uterine binding of oxytocin, increases the sensitivity of the myometrium to oxytocin. The myometrium binds the most oxytocin at estrus and is most sensitive to oxtocin at that time. The dgree of stimulation by oxytocin of prostaglandin F2alpha synthesis by ewe endometrium is paralleled by an increased concentration of oxytocin binding sites. The marked increase in sensitivity to oxytocin of the rat uterus occurring on the day of parturition also is reflected by the amount of oxytocin bound by the uterus. Because of the many correlations between oxytocin binding and bioactivity, it appears that oxytocin binding sites on the plasma membrane of target cells constitute the recognition part of oxytocin receptors.", "contents": "Characterization of oxytocin receptors in the uterus and mammary gland. High affinity binding sites for 3[H] oxytocin have been demonstrated in particulate fractions from rat uterus and oviduct, myometrium from the sow, ewe and human, ewe endometrium, and mammary gland from the lactating rat. The binding activity has been localized to enriched plasma membrane fractions from the rat uterus and mammary gland; cells isolated from the mammary gland also bind oxytocin. The apparent dissociation constant (Kd) for the interaction of oxytocin with its binding sites in a variety of tissue preparations is in the nanomolar range. The concentration of oxytocin eliciting half-maximal contraction of the rat isolated uterus corresponds to the apparent Kd of oxytocin interaction with uterine particulate fractions. Binding is specific with respect to the target tissue or cell, as well as to the ligand. The affinity of binding sites for oxytocin analogues corresponds generally to their potencies as agonists or antagonists. Factors that affect the binding of oxytocin affect the biological response in the same way. For example, certain divalent metal ions, which increase oxytocin binding activity, enhance the sensitivity of the contractile response of the uterus and mammary gland to oxytocin. Estrogen administration, which increases the uterine binding of oxytocin, increases the sensitivity of the myometrium to oxytocin. The myometrium binds the most oxytocin at estrus and is most sensitive to oxtocin at that time. The dgree of stimulation by oxytocin of prostaglandin F2alpha synthesis by ewe endometrium is paralleled by an increased concentration of oxytocin binding sites. The marked increase in sensitivity to oxytocin of the rat uterus occurring on the day of parturition also is reflected by the amount of oxytocin bound by the uterus. Because of the many correlations between oxytocin binding and bioactivity, it appears that oxytocin binding sites on the plasma membrane of target cells constitute the recognition part of oxytocin receptors."}
{"id": "PMID:192602", "title": "Cyclic nucleotides in the cellular action of neurohypophyseal hormones.", "content": "Cyclic 3',5'-nucleotides play an important role in the action of neurohypophyseal hormones on peripheral tissues. All available evidence indicates that cyclic AMP serves as an intracellular mediator in the regulatory action of neurohypophyseal hormones on transport of fluids and solutes across both mammalian and nonmammalian epithelial membranes. There is a close association among binding of neurohypophyseal hormones on membrane, stimulation of cyclic AMP generation, and the functional response. On the other hand, neurohypophyseal hormones have no similar effect on cyclic AMP metabolism in contractile tissues such as smooth muscle. It appears likely that neurohypophyseal hormones stimulate primarily generation of cyclic GMP in contractile tissues, and the increase in cyclic GMP levels may be associated with the contractile response. While the role of cyclic AMP in neurohypophyseal hormone effects in epithelia is firmly established, the possible role of cyclic GMP in contractile responses is largely hypothetical at the present time.", "contents": "Cyclic nucleotides in the cellular action of neurohypophyseal hormones. Cyclic 3',5'-nucleotides play an important role in the action of neurohypophyseal hormones on peripheral tissues. All available evidence indicates that cyclic AMP serves as an intracellular mediator in the regulatory action of neurohypophyseal hormones on transport of fluids and solutes across both mammalian and nonmammalian epithelial membranes. There is a close association among binding of neurohypophyseal hormones on membrane, stimulation of cyclic AMP generation, and the functional response. On the other hand, neurohypophyseal hormones have no similar effect on cyclic AMP metabolism in contractile tissues such as smooth muscle. It appears likely that neurohypophyseal hormones stimulate primarily generation of cyclic GMP in contractile tissues, and the increase in cyclic GMP levels may be associated with the contractile response. While the role of cyclic AMP in neurohypophyseal hormone effects in epithelia is firmly established, the possible role of cyclic GMP in contractile responses is largely hypothetical at the present time."}
{"id": "PMID:192603", "title": "Indentification of sites in oxytocin involved in uterine receptor recognition and activation.", "content": "Following a brief review of the preferred three-dimensional structured proposed for oxytocin in dimethylsulfoxide and in aqueous medium, the \"cooperative model\" for the biologically active conformation of oxytocin is discussed. An approach to conformation-activity analysis is described. The importance of determining the peptide backbone conformation and the functional contribution of peptide backbone and amino acid side chains to hormone receptor interactions are analyzed. Sites are proposed that are thought to be involved in the binding process of oxytocin to the smooth muscle receptor in rat uterus, as well as sites that are thought to be responsible for receptor activation.", "contents": "Indentification of sites in oxytocin involved in uterine receptor recognition and activation. Following a brief review of the preferred three-dimensional structured proposed for oxytocin in dimethylsulfoxide and in aqueous medium, the \"cooperative model\" for the biologically active conformation of oxytocin is discussed. An approach to conformation-activity analysis is described. The importance of determining the peptide backbone conformation and the functional contribution of peptide backbone and amino acid side chains to hormone receptor interactions are analyzed. Sites are proposed that are thought to be involved in the binding process of oxytocin to the smooth muscle receptor in rat uterus, as well as sites that are thought to be responsible for receptor activation."}
{"id": "PMID:192604", "title": "The biological effects of polybrominated biphenyls in avian species.", "content": "Polybrominated biphenyl (PBB), structurally similar to polychlorinated biphenyl (PCB), affects feed intake, egg production, and hatchability of fertile eggs in chickens and quail. Subcutaneous edema of the neck and shoulder are common abnormalities of hatched chicks from PBB-fed dams. No characteristic teratogenicity is evident. Offspring hatched are less viable during their first 3 weeks of life. PBB does not produce thinner egg shells or lower egg weights. The ratio of PBB egg content to dietary level is 1.3-1.5:1.0. The biological half-life of PBB in eggs is calculated to be 17 days. Tissue residues are higher in males than females because egg production is a major excretory route for PBB. Polybrominated biphenyl feeding causes tissue changes in size, structure and/or function in the liver, thyroid, testes, comb, heart, spleen, bursa of Fabricus, and blood. Liver enlargement, porphyria and microsomal enzyme induction results from PBB administration. The spleen, bursa and comb are reduced in size, whereas the thyroid increases after PBB feeding. A characteristic of PBB and PCB toxicity is hydropericardium and general edema.", "contents": "The biological effects of polybrominated biphenyls in avian species. Polybrominated biphenyl (PBB), structurally similar to polychlorinated biphenyl (PCB), affects feed intake, egg production, and hatchability of fertile eggs in chickens and quail. Subcutaneous edema of the neck and shoulder are common abnormalities of hatched chicks from PBB-fed dams. No characteristic teratogenicity is evident. Offspring hatched are less viable during their first 3 weeks of life. PBB does not produce thinner egg shells or lower egg weights. The ratio of PBB egg content to dietary level is 1.3-1.5:1.0. The biological half-life of PBB in eggs is calculated to be 17 days. Tissue residues are higher in males than females because egg production is a major excretory route for PBB. Polybrominated biphenyl feeding causes tissue changes in size, structure and/or function in the liver, thyroid, testes, comb, heart, spleen, bursa of Fabricus, and blood. Liver enlargement, porphyria and microsomal enzyme induction results from PBB administration. The spleen, bursa and comb are reduced in size, whereas the thyroid increases after PBB feeding. A characteristic of PBB and PCB toxicity is hydropericardium and general edema."}
{"id": "PMID:192606", "title": "[Mechanisms of participation of the sensomotor cortex in controlling movements].", "content": "Neuromorphological, neurophysiological and biomechanical studies in cats revealed cortical structural neuronal modules and functional units of different grades of complexity. Single systemic principle was determined for the sensorimotor cortex activity: structurally organized neuronal modules, having distributed outputs, can be involved in different functional units for purposeful movements. Specific lemniscal signals concerning the movements are the factor which filters inflow of teleceptive information to the neuronal modules and determines exact torographical relations of cortical motor outputs.", "contents": "[Mechanisms of participation of the sensomotor cortex in controlling movements]. Neuromorphological, neurophysiological and biomechanical studies in cats revealed cortical structural neuronal modules and functional units of different grades of complexity. Single systemic principle was determined for the sensorimotor cortex activity: structurally organized neuronal modules, having distributed outputs, can be involved in different functional units for purposeful movements. Specific lemniscal signals concerning the movements are the factor which filters inflow of teleceptive information to the neuronal modules and determines exact torographical relations of cortical motor outputs."}
{"id": "PMID:192607", "title": "[Sensitivity to adrenocorticotropic hormone during adaptation to increased muscle activity].", "content": "Systematical muscle exercises increased sensitivity of adrenals to ACTH in adult albino rats, while fatigue decreased it. The sensitivity of adenylatecyclase of fat cells to ACTH does not change during the adaptation of organism to increased muscular activity. Activation of adenylate cyclase of fat cells with epinephrine is abolished by sympatholytin which, however, has no effect on the ACTH activation. These findings confirm that the adenylate cyclase receptors for epinephrine and for ACTH are different.", "contents": "[Sensitivity to adrenocorticotropic hormone during adaptation to increased muscle activity]. Systematical muscle exercises increased sensitivity of adrenals to ACTH in adult albino rats, while fatigue decreased it. The sensitivity of adenylatecyclase of fat cells to ACTH does not change during the adaptation of organism to increased muscular activity. Activation of adenylate cyclase of fat cells with epinephrine is abolished by sympatholytin which, however, has no effect on the ACTH activation. These findings confirm that the adenylate cyclase receptors for epinephrine and for ACTH are different."}
{"id": "PMID:192610", "title": "The effect of insulin treatment on the metabolic response to glucagon in diabetes.", "content": "The metabolic response to intravenous glucagon was studied in insulin requiring diabetes before, 1 week and 1 month after treatment with insulin. The rise in plasma 3-hydroxybutyrate following glucagon in the untreated state was converted to a fall after 1 month on insulin. It is suggested that this response could provide a measure of the biological effectiveness of circulating insulin. There was no change in plasma cyclic AMP response to glucagon after treatment with insulin.", "contents": "The effect of insulin treatment on the metabolic response to glucagon in diabetes. The metabolic response to intravenous glucagon was studied in insulin requiring diabetes before, 1 week and 1 month after treatment with insulin. The rise in plasma 3-hydroxybutyrate following glucagon in the untreated state was converted to a fall after 1 month on insulin. It is suggested that this response could provide a measure of the biological effectiveness of circulating insulin. There was no change in plasma cyclic AMP response to glucagon after treatment with insulin."}
{"id": "PMID:192611", "title": "Androgen stimulation of prolactin receptors in rat prostate.", "content": "Specific receptors for iodine-labelled human prolactin ([125I]hPrl) are present in membrane preparations of the rat ventral prostate. The binding is saturable with an apparent association constant (Ka) of 2.2 X 10(9) M-1 and a binding capacity of about 1 pmol/100mg prostatic tissue. The binding of [125I]hPrl is inhibited by hPrl, ovine Prl (otprl) and human growth hormone, but not by ovine FSH or LH. Serum from rats having Prl-producing pituitary tumors caused a displacement of the [125I]hPrl from the receptors, and the displacement curve was parallel with that of the hPrl standard. Treatment of immature rats with varying doses of dihydrotestosterone propionate (10-5000 microng) causes a dose-dependent stimulation of Prl receptors calculated both as binding sites per mg of membrane protein and as binding sites per prostate. Androgen stimulation of prostatic Prl receptors increases the tissue sensitivity for circulating Prl and may be one reason for the known increases in endogenous cAMP levels in prostatic tissue after androgen treatment in vivo.", "contents": "Androgen stimulation of prolactin receptors in rat prostate. Specific receptors for iodine-labelled human prolactin ([125I]hPrl) are present in membrane preparations of the rat ventral prostate. The binding is saturable with an apparent association constant (Ka) of 2.2 X 10(9) M-1 and a binding capacity of about 1 pmol/100mg prostatic tissue. The binding of [125I]hPrl is inhibited by hPrl, ovine Prl (otprl) and human growth hormone, but not by ovine FSH or LH. Serum from rats having Prl-producing pituitary tumors caused a displacement of the [125I]hPrl from the receptors, and the displacement curve was parallel with that of the hPrl standard. Treatment of immature rats with varying doses of dihydrotestosterone propionate (10-5000 microng) causes a dose-dependent stimulation of Prl receptors calculated both as binding sites per mg of membrane protein and as binding sites per prostate. Androgen stimulation of prostatic Prl receptors increases the tissue sensitivity for circulating Prl and may be one reason for the known increases in endogenous cAMP levels in prostatic tissue after androgen treatment in vivo."}
{"id": "PMID:192612", "title": "HCG-dependent regulation of gonadotropin receptor sites: negative control in testicular Leydig cells.", "content": "A single injection of human chorionic gonadotropin (hCG 500 IU) to prepubertal male rats increases plasma testosterone level and decreases hCG receptors in the testicular Leydig cells for more than 120 h. Injected hCG, measured in plasma using a specific radioreceptor assay for gonadotropins, is maximal at 2 h and decreases thereafter with an apparent half-life of 16 h. Plasma testosterone exhibits a rapid increase (30-40 ng/ml) within 1h after hCG injection. A delayed paradoxical increase (20-30 ng/ml) is observed between 48 and 120 h after the injection. The number of hCG binding sites in the isolated Leydig cells membranes decreases to less than 10% of the control value within 10 h and remains almost undetectable until 96 h after hCG injection. Reappearance of the binding sites is observed around 120 h. Similar, but less pronounced effects are found after the injection of 10 IU hCG. Since receptor occupancy cannot explain such a phenomenon, it is concluded that hCG is exerting a negative control on its own receptors in the Leydig cells.", "contents": "HCG-dependent regulation of gonadotropin receptor sites: negative control in testicular Leydig cells. A single injection of human chorionic gonadotropin (hCG 500 IU) to prepubertal male rats increases plasma testosterone level and decreases hCG receptors in the testicular Leydig cells for more than 120 h. Injected hCG, measured in plasma using a specific radioreceptor assay for gonadotropins, is maximal at 2 h and decreases thereafter with an apparent half-life of 16 h. Plasma testosterone exhibits a rapid increase (30-40 ng/ml) within 1h after hCG injection. A delayed paradoxical increase (20-30 ng/ml) is observed between 48 and 120 h after the injection. The number of hCG binding sites in the isolated Leydig cells membranes decreases to less than 10% of the control value within 10 h and remains almost undetectable until 96 h after hCG injection. Reappearance of the binding sites is observed around 120 h. Similar, but less pronounced effects are found after the injection of 10 IU hCG. Since receptor occupancy cannot explain such a phenomenon, it is concluded that hCG is exerting a negative control on its own receptors in the Leydig cells."}
{"id": "PMID:192613", "title": "Active transport of iodide in isolated porcine thyroid cells. Application to an in vitro bioassay of thyrotropin.", "content": "Porcine thyroid cells were cultured for 2 days with or without dibutyryl cyclic AMP or thyrotropin (TSH). Then they were isolated post-culture by a gentle treatment with a calcium chelating agent. Some characteristics of the iodide transport system were studied in these thyroid cell suspensions. Iodide influx is a saturable, temperature- and energy-dependent phenomenon. It is blocked by ouaba\u00efn, N-ethylmaleimide, dinitrophenol, cardiotoxin, low Na+ concentration and harmaline. Only 3% of the intracellular iodide is trichloracetic-acid-insoluble at equilibrium. The apparent Michaelis constant (Km) of the transport system is 30 micronM. For monolayer cells, the decrease of C/M ratio, increase of apparent Km, and decrease of Vmax between day 0 (freshly isolated cells) and day 6, indicate a loss of iodide-trapping ability up to passive diffusion. To the contrary, high values of C/M and normal Km (30 micronM) are observed in TSH follicles from reassociated cells. At iodide equilibrium, thryotropin, prostaglandins E1 and E2 and long-acting thyroid stimulator (LATS), induce a fast release of iodide. This release is dose-dependent in the first 5 min. It has been used to develop a bioassay of TSH and a fast detection of LATS.", "contents": "Active transport of iodide in isolated porcine thyroid cells. Application to an in vitro bioassay of thyrotropin. Porcine thyroid cells were cultured for 2 days with or without dibutyryl cyclic AMP or thyrotropin (TSH). Then they were isolated post-culture by a gentle treatment with a calcium chelating agent. Some characteristics of the iodide transport system were studied in these thyroid cell suspensions. Iodide influx is a saturable, temperature- and energy-dependent phenomenon. It is blocked by ouaba\u00efn, N-ethylmaleimide, dinitrophenol, cardiotoxin, low Na+ concentration and harmaline. Only 3% of the intracellular iodide is trichloracetic-acid-insoluble at equilibrium. The apparent Michaelis constant (Km) of the transport system is 30 micronM. For monolayer cells, the decrease of C/M ratio, increase of apparent Km, and decrease of Vmax between day 0 (freshly isolated cells) and day 6, indicate a loss of iodide-trapping ability up to passive diffusion. To the contrary, high values of C/M and normal Km (30 micronM) are observed in TSH follicles from reassociated cells. At iodide equilibrium, thryotropin, prostaglandins E1 and E2 and long-acting thyroid stimulator (LATS), induce a fast release of iodide. This release is dose-dependent in the first 5 min. It has been used to develop a bioassay of TSH and a fast detection of LATS."}
{"id": "PMID:192614", "title": "Thyrotropin-specific binding to human peripheral blood monocytes and polymorphonuclear leukocytes.", "content": "[125I]Labeled thyrotropin binding to leukocytes has been studied using lymphocyte-, monocyte- and polymorphonuclear leukocytes-enriched preparations obtained by centrifugation of Ficoll-Angiocontrix gradients and Sephadex G-10 adherence. From the relation between thyrotropin binding and phagocytosis as shown by latex beads ingestion, it is concluded that the hormone binds essentially to monocytes and polymorphonuclear leukocytes. Equilibrium association constants of the high-affinity, low-capacity sites (1 nM-1) are similar to those found in isolated thyroid cells or in thyroid plasma membranes. The role of thyrotropin in the regulation of phagocytosis by leukocytes is discussed.", "contents": "Thyrotropin-specific binding to human peripheral blood monocytes and polymorphonuclear leukocytes. [125I]Labeled thyrotropin binding to leukocytes has been studied using lymphocyte-, monocyte- and polymorphonuclear leukocytes-enriched preparations obtained by centrifugation of Ficoll-Angiocontrix gradients and Sephadex G-10 adherence. From the relation between thyrotropin binding and phagocytosis as shown by latex beads ingestion, it is concluded that the hormone binds essentially to monocytes and polymorphonuclear leukocytes. Equilibrium association constants of the high-affinity, low-capacity sites (1 nM-1) are similar to those found in isolated thyroid cells or in thyroid plasma membranes. The role of thyrotropin in the regulation of phagocytosis by leukocytes is discussed."}
{"id": "PMID:192615", "title": "Binding characteristics of L-triiodothyronine to isolated rat liver chromatin.", "content": "The binding characteristics of [125I]-labeled L-triiodothyronine (T3) to chromatin isolated from rat liver nuclei were investigated. Binding of T3 to chromatin showed temperature-, incubation time-, and DNA concentration-dependence. According to Scatchard analysis, the apparent equilibrium dissociation constant was 225 pM, with a maximum binding capacity of about 0.2 pmoles per mg DNA. Displacement studies with unlabeled thyroxine (T4) and T3 showed that the binding sites for T4 might be the same as T3 but the binding affinity of the former was less than that of the latter. The binding was completely inhibited by the eukaryotic RNA polymerase inhibitor, rifampicin AF/021, but not by the prokaryotic inhibitor, rifampicin and alpha-amanitin. These observations indicate that the receptors for T3 have certain properties in common with RNA polymerase or other enzyme proteins which are sensitive to the rifampicin derivative. The hormone--chromatin fragments complex was solubilized from residual chromatin by digestion with DNase, but not with RNase, suggesting that the T3 receptors localize in the DNase-sensitive regions of DNA in the chromatin. This provides a useful method to use to investigate the localization of the receptor proteins in the chromatin and the interaction of the hormone-receptor complex with DNA.", "contents": "Binding characteristics of L-triiodothyronine to isolated rat liver chromatin. The binding characteristics of [125I]-labeled L-triiodothyronine (T3) to chromatin isolated from rat liver nuclei were investigated. Binding of T3 to chromatin showed temperature-, incubation time-, and DNA concentration-dependence. According to Scatchard analysis, the apparent equilibrium dissociation constant was 225 pM, with a maximum binding capacity of about 0.2 pmoles per mg DNA. Displacement studies with unlabeled thyroxine (T4) and T3 showed that the binding sites for T4 might be the same as T3 but the binding affinity of the former was less than that of the latter. The binding was completely inhibited by the eukaryotic RNA polymerase inhibitor, rifampicin AF/021, but not by the prokaryotic inhibitor, rifampicin and alpha-amanitin. These observations indicate that the receptors for T3 have certain properties in common with RNA polymerase or other enzyme proteins which are sensitive to the rifampicin derivative. The hormone--chromatin fragments complex was solubilized from residual chromatin by digestion with DNase, but not with RNase, suggesting that the T3 receptors localize in the DNase-sensitive regions of DNA in the chromatin. This provides a useful method to use to investigate the localization of the receptor proteins in the chromatin and the interaction of the hormone-receptor complex with DNA."}
{"id": "PMID:192616", "title": "Monozygotic triplets with discordance for diabetes mellitus and diabetic microangiopathy.", "content": "A set of monozygotic triplets (PE.K., P.K., S.K.) has been studied. There is no diabetes in first-degree relatives. PE.K. developed insulin-requiring (60 U. NPH) diabetes at the age of 13 years. Over a period of 11 years since that time, numerous studies of insulin and growth-hormone secretion were performed on P.K. and S.K., including multiple oral glucose tolerance tests (OGTTs), cortisone-primed oral glucose tolerance tests (C-OGTTs), intravenous glucose tolerance tests (IVGTTs), and intravenous tolbutamide tests (IVTTs). The results of each test were compared with age- and sex-matched control subjects. P. K. developed insulin-requiring (56 U. NPH) diabetes after remaining discordant for eight years. Glucose, insilin, and growth-hormone responses during all tests were normal except during the IVGTT performed four months prior to the onset of diabetes. This last IVGTT revealed a glucose disappearance rate of 0.98 per cent per minute, and the slope of the regression line of serum-insulin response (IRI) on blood glucose (BG) was markedly decreased to 0.005 micronU./ml. IRI/mg./dl. BG (controls 0.340 +/- 0.04; mean +/- S.E.M.). The insulin responses in P.K. and S.K. were similar during all OGTTs, C-OGTTs, and IVTTs. S.K. has continued to maintain normal glucose tolerance and normal insulin and growth-hormone responses during all tests. The histocompability antigen studies have revealed HLA-A2, AW24, BW15, and BW40 phenotype in these monozygotic triplets. Muscle capillary basement membranes of the nondiabetic triplet were normal, whereas both diabetic triplets manifested evidence of capillary basement membrane thickening. The clinical and biochemical profiles in these triplets and the capillary basement membrane data lend strong credence to the role of \"nongenetic\" determinants in the development of \"genetic\" diabetes as well as diabetic microangiopathy in juvenile-onset-type diabetes.", "contents": "Monozygotic triplets with discordance for diabetes mellitus and diabetic microangiopathy. A set of monozygotic triplets (PE.K., P.K., S.K.) has been studied. There is no diabetes in first-degree relatives. PE.K. developed insulin-requiring (60 U. NPH) diabetes at the age of 13 years. Over a period of 11 years since that time, numerous studies of insulin and growth-hormone secretion were performed on P.K. and S.K., including multiple oral glucose tolerance tests (OGTTs), cortisone-primed oral glucose tolerance tests (C-OGTTs), intravenous glucose tolerance tests (IVGTTs), and intravenous tolbutamide tests (IVTTs). The results of each test were compared with age- and sex-matched control subjects. P. K. developed insulin-requiring (56 U. NPH) diabetes after remaining discordant for eight years. Glucose, insilin, and growth-hormone responses during all tests were normal except during the IVGTT performed four months prior to the onset of diabetes. This last IVGTT revealed a glucose disappearance rate of 0.98 per cent per minute, and the slope of the regression line of serum-insulin response (IRI) on blood glucose (BG) was markedly decreased to 0.005 micronU./ml. IRI/mg./dl. BG (controls 0.340 +/- 0.04; mean +/- S.E.M.). The insulin responses in P.K. and S.K. were similar during all OGTTs, C-OGTTs, and IVTTs. S.K. has continued to maintain normal glucose tolerance and normal insulin and growth-hormone responses during all tests. The histocompability antigen studies have revealed HLA-A2, AW24, BW15, and BW40 phenotype in these monozygotic triplets. Muscle capillary basement membranes of the nondiabetic triplet were normal, whereas both diabetic triplets manifested evidence of capillary basement membrane thickening. The clinical and biochemical profiles in these triplets and the capillary basement membrane data lend strong credence to the role of \"nongenetic\" determinants in the development of \"genetic\" diabetes as well as diabetic microangiopathy in juvenile-onset-type diabetes."}
{"id": "PMID:192617", "title": "Potentiation of the hepatic action of insulin by chlorpropamide.", "content": "In perfused livers of fed rats, chlorpropamide inhibits glucagon-stimulated glucose production by augmenting the action of insulin. This effect is associated with a decrease in cyclic AMP accumulation in liver and perfusate. Alterations in glucose production appear to correlate more closely with changes in the amount of cyclic AMP in the perfusate than with changes in intrahepatic concentration of nucleotide. Potenitation by chlorpropamide of the hepatic action of insulin does not require administration of the drug prior to perfusion. Further, it is demonstrable at concentrations of insulin and glucagon (10(-11M) that approximate the normal plasma levels of these hormones.", "contents": "Potentiation of the hepatic action of insulin by chlorpropamide. In perfused livers of fed rats, chlorpropamide inhibits glucagon-stimulated glucose production by augmenting the action of insulin. This effect is associated with a decrease in cyclic AMP accumulation in liver and perfusate. Alterations in glucose production appear to correlate more closely with changes in the amount of cyclic AMP in the perfusate than with changes in intrahepatic concentration of nucleotide. Potenitation by chlorpropamide of the hepatic action of insulin does not require administration of the drug prior to perfusion. Further, it is demonstrable at concentrations of insulin and glucagon (10(-11M) that approximate the normal plasma levels of these hormones."}
{"id": "PMID:192618", "title": "Metabolic approaches to studies on diabetic microangiopathy.", "content": "The chief purposes of this report are (a) to focus attention on various metabolic and pathophysiologic parameters relating prostaglandins (PGs) and thromboxanes to the slow but inexorable progression of vascular and blood cell dysfunction in diabetes mellitus and (b) to suggest areas of investigation that may be of fundamental importance for expanded areas of diabetes research. The prime thrust of these investigations would be to correlate these metabolic and pathophysiologic parameters with the vasculopathy of diabetes mellitus.", "contents": "Metabolic approaches to studies on diabetic microangiopathy. The chief purposes of this report are (a) to focus attention on various metabolic and pathophysiologic parameters relating prostaglandins (PGs) and thromboxanes to the slow but inexorable progression of vascular and blood cell dysfunction in diabetes mellitus and (b) to suggest areas of investigation that may be of fundamental importance for expanded areas of diabetes research. The prime thrust of these investigations would be to correlate these metabolic and pathophysiologic parameters with the vasculopathy of diabetes mellitus."}
{"id": "PMID:192619", "title": "Sleep state, apnea and bradycardia in pre-term infants.", "content": "Respiratory pattern and heart rate were studied in 28 pre-term infants and four full-term infants during the first weeks of life. Sleep state was identified by standard neurological and EEG criteria. Apneic spells lasting 10 seconds or more were most frequent in the least mature infants, and their frequency tended to diminish with increasing maturity. When these apneic attacks were related to sleep state they were found to occur more frequently during non-REM sleep in infants of 30 to 33 weeks gestation. This was the only statistically significant difference found. No over-all pattern relating sleep state to frequency of apnea could be detected for individual infants. It was also difficult to relate the occurrence of bradycardia to apnea in terms of sleep state or gestational age. It is concluded that no simple relationship between sleep state, apnea and bradycardia exists and that a complex interrelation between central and peripheral factors is involved in these events.", "contents": "Sleep state, apnea and bradycardia in pre-term infants. Respiratory pattern and heart rate were studied in 28 pre-term infants and four full-term infants during the first weeks of life. Sleep state was identified by standard neurological and EEG criteria. Apneic spells lasting 10 seconds or more were most frequent in the least mature infants, and their frequency tended to diminish with increasing maturity. When these apneic attacks were related to sleep state they were found to occur more frequently during non-REM sleep in infants of 30 to 33 weeks gestation. This was the only statistically significant difference found. No over-all pattern relating sleep state to frequency of apnea could be detected for individual infants. It was also difficult to relate the occurrence of bradycardia to apnea in terms of sleep state or gestational age. It is concluded that no simple relationship between sleep state, apnea and bradycardia exists and that a complex interrelation between central and peripheral factors is involved in these events."}
{"id": "PMID:192620", "title": "Effect of experimental diabetes and glucagon on cAMP-dependent protein kinase in rat liver.", "content": "Liver protein kinase was determined in the absence and presence of cAMP4. Experimental alloxan diabetes resulted in a decrease in total protein kinase (+cAMP) and an increase in the activity ratio (-cAMP) divided by (+cAMP) in liver. Insulin treatment of diabetic rats reversed the observed changes in protein kinase in liver. Glucagon administered in vivo to normal rats caused an increase in the activity ratio and a decrease in total protein kinase activity in liver. The changes are similar to those in diabetes. A decrease in the ratio of insulin to glucagon in diabetes may account for the changes in protein kinase observed.", "contents": "Effect of experimental diabetes and glucagon on cAMP-dependent protein kinase in rat liver. Liver protein kinase was determined in the absence and presence of cAMP4. Experimental alloxan diabetes resulted in a decrease in total protein kinase (+cAMP) and an increase in the activity ratio (-cAMP) divided by (+cAMP) in liver. Insulin treatment of diabetic rats reversed the observed changes in protein kinase in liver. Glucagon administered in vivo to normal rats caused an increase in the activity ratio and a decrease in total protein kinase activity in liver. The changes are similar to those in diabetes. A decrease in the ratio of insulin to glucagon in diabetes may account for the changes in protein kinase observed."}
{"id": "PMID:192621", "title": "Permissive effect of glucose on the glucagon-induced accumulation of cAMP in isolated rat pancreatic islets.", "content": "Glucose stimulation increased the cAMP content of collagenase-isolated rat pancreatic islets fourfold above baseline values. The elevation was transient, lasting about 5 min, and was dose-dependent. Insulin release continued at a constant rate throughout the incubation. Glucagon, in the absence of glucose, increased cAMP for about 1 min but only slightly, and had no effect on insulin release. In the presence of glucose, however, glucagon enhanced islet cAMP content 15-fold and increased the release of insulin. Glucagon was most effective at high glucose concentrations (16.6 and 25 mM). This indicates that glucagon is critically dependent on the presence of glucose in order to increase the islet cAMP content and to stimulate insulin release. The inability of glucagon to generate sufficient cAMP in the absence of glucose might be one of the reasons why the hormone is a potentiator rather than an initiator of insulin release.", "contents": "Permissive effect of glucose on the glucagon-induced accumulation of cAMP in isolated rat pancreatic islets. Glucose stimulation increased the cAMP content of collagenase-isolated rat pancreatic islets fourfold above baseline values. The elevation was transient, lasting about 5 min, and was dose-dependent. Insulin release continued at a constant rate throughout the incubation. Glucagon, in the absence of glucose, increased cAMP for about 1 min but only slightly, and had no effect on insulin release. In the presence of glucose, however, glucagon enhanced islet cAMP content 15-fold and increased the release of insulin. Glucagon was most effective at high glucose concentrations (16.6 and 25 mM). This indicates that glucagon is critically dependent on the presence of glucose in order to increase the islet cAMP content and to stimulate insulin release. The inability of glucagon to generate sufficient cAMP in the absence of glucose might be one of the reasons why the hormone is a potentiator rather than an initiator of insulin release."}
{"id": "PMID:192624", "title": "A spontaneous transplantable osteogenic sarcoma in AKR/Ms mice.", "content": "A transplantable osteogenic sarcoma originally arising in the right femur of an AKR/Ms male mouse is described. The original tumor showed a conspicuous bone and cartilage formation, but the capability of forming the bone was lost in the 4th transplant generation and that of cartilage formation was lost in the 7th generation. Alkaline phosphatase activity was histochemically demonstrated in only a few tumor cells, and the activity did not rise in the host serum. Intracisternal type-A particles of an average diameter of 70 nm were abundant in the rough endoplasmic reticulum, while type-C particles were rarely found to be budding from the cell surface or free in the extracellular spaces by electron microscopy. Three of the 27 thymectomized AKR mice that had been neonatally injected with cell-free material of the transplanted tumor developed osteomas, but no osteogenic sarcoma was found.", "contents": "A spontaneous transplantable osteogenic sarcoma in AKR/Ms mice. A transplantable osteogenic sarcoma originally arising in the right femur of an AKR/Ms male mouse is described. The original tumor showed a conspicuous bone and cartilage formation, but the capability of forming the bone was lost in the 4th transplant generation and that of cartilage formation was lost in the 7th generation. Alkaline phosphatase activity was histochemically demonstrated in only a few tumor cells, and the activity did not rise in the host serum. Intracisternal type-A particles of an average diameter of 70 nm were abundant in the rough endoplasmic reticulum, while type-C particles were rarely found to be budding from the cell surface or free in the extracellular spaces by electron microscopy. Three of the 27 thymectomized AKR mice that had been neonatally injected with cell-free material of the transplanted tumor developed osteomas, but no osteogenic sarcoma was found."}
{"id": "PMID:192622", "title": "[Aspecific inhibitors of rubella virus hemagglutination in normal and thyroidectomized rats].", "content": "Thyroidectomized rats show alterations in serum lipoprotein distribution with an high increase of low density lipoproteins (LDL): however inhibitors titre was the same both in control and in treated animals. Also removal of nonspecific inhibitors by precipitation with heparin-MnCl2 or D.S. CaCl2 methods did not show differences between control and treated animals.", "contents": "[Aspecific inhibitors of rubella virus hemagglutination in normal and thyroidectomized rats]. Thyroidectomized rats show alterations in serum lipoprotein distribution with an high increase of low density lipoproteins (LDL): however inhibitors titre was the same both in control and in treated animals. Also removal of nonspecific inhibitors by precipitation with heparin-MnCl2 or D.S. CaCl2 methods did not show differences between control and treated animals."}
{"id": "PMID:192623", "title": "[Hemagglutinating activity of various viruses on trypsinized erythrocytes].", "content": "Mengo, Vesicular stomatitis and Semliki forest viruses titered with trypsin modified mouse, goose, pigeon and human erythrocytes show HA titers 2-32 fold higher than with the same untreated cells.", "contents": "[Hemagglutinating activity of various viruses on trypsinized erythrocytes]. Mengo, Vesicular stomatitis and Semliki forest viruses titered with trypsin modified mouse, goose, pigeon and human erythrocytes show HA titers 2-32 fold higher than with the same untreated cells."}
{"id": "PMID:192626", "title": "Antibody to hepatitis B core antigen in patients with hepatocellular carcinoma.", "content": "Hepatitis B surface antigen (HBsAg), anti-HBs, and anti-HB core (HBc) were measured in 124 patients with hepatocellular carcinoma (HCC) in comparison with 299 control subjects of comparable ages, and in 48 cases of chronic hepatitis and 52 cases of hepatic cirrhosis. It was found that 72.6% of the HCC patients were positive for anti-HBc, and 80.6% were positive for at least one test, whereas in the control, anti-HBc was positive in 30.1% and 34.1% were positive for at least one test, the differences between the two groups being significant (P less than 0.01). The frequencies of positive tests for HBsAg and anti-HBc were the highest in HCC followed in decreasing order by cirrhosis, chronic hepatitis and the control group. A possible role of HB virus infection in hepatocellular carcinoma is discussed in relation to other factors.", "contents": "Antibody to hepatitis B core antigen in patients with hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg), anti-HBs, and anti-HB core (HBc) were measured in 124 patients with hepatocellular carcinoma (HCC) in comparison with 299 control subjects of comparable ages, and in 48 cases of chronic hepatitis and 52 cases of hepatic cirrhosis. It was found that 72.6% of the HCC patients were positive for anti-HBc, and 80.6% were positive for at least one test, whereas in the control, anti-HBc was positive in 30.1% and 34.1% were positive for at least one test, the differences between the two groups being significant (P less than 0.01). The frequencies of positive tests for HBsAg and anti-HBc were the highest in HCC followed in decreasing order by cirrhosis, chronic hepatitis and the control group. A possible role of HB virus infection in hepatocellular carcinoma is discussed in relation to other factors."}
{"id": "PMID:192627", "title": "Cytomegalovirus inclusions in patients with ulcerative colitis and toxic dilation requiring colonic resection.", "content": "Microscopic examination of 50 colon resection specimens from 46 patients with ulcerative colitis revealed 6 patients whose colons contained intranuclear inclusions characteristic for cytomegalovirus (CMV). All patients were male, 47 years of age or older, and all had marked severe and fulminating courses. Five of the 6 patients had toxic dilation of the colon. Three of our patients had received no steroid therapy before their toxic dilation, however, all received steroids during attempts at medical management. Two other patients were found to have toxic dilation of the colon among our 46 patients, however, no evidence of CMV could be found in these 2 cases. There were 6 patients without toxic dilation whose colon specimens showed destructive inflammation and granulation tissue extending into the muscularis propria or transmurally. None of the colons from these 6 patients contained CMV inclusions. In our patients, the finding of CMV may be coincidental, but it is suggested that in our group of patients with ulcerative colitis, the CMV may play a role in altering the clinical course of these patients.", "contents": "Cytomegalovirus inclusions in patients with ulcerative colitis and toxic dilation requiring colonic resection. Microscopic examination of 50 colon resection specimens from 46 patients with ulcerative colitis revealed 6 patients whose colons contained intranuclear inclusions characteristic for cytomegalovirus (CMV). All patients were male, 47 years of age or older, and all had marked severe and fulminating courses. Five of the 6 patients had toxic dilation of the colon. Three of our patients had received no steroid therapy before their toxic dilation, however, all received steroids during attempts at medical management. Two other patients were found to have toxic dilation of the colon among our 46 patients, however, no evidence of CMV could be found in these 2 cases. There were 6 patients without toxic dilation whose colon specimens showed destructive inflammation and granulation tissue extending into the muscularis propria or transmurally. None of the colons from these 6 patients contained CMV inclusions. In our patients, the finding of CMV may be coincidental, but it is suggested that in our group of patients with ulcerative colitis, the CMV may play a role in altering the clinical course of these patients."}
{"id": "PMID:192628", "title": "Transpyloric prolapse of polypoid gastric carcinoma.", "content": "Four patients with discrete intraluminal filling defects in the duodenal bulb secondary to transpyloric prolapse of polypoid gastric carcinoma are reported. The lesions were pedunculated in 2 cases and sessile in the remaining 2. The clinical, radiological,and pathological findings are discussed. Prolapsed gastric carcinoma should be included in the differential diagnosis of localized intraluminal filling defects in the duodenal bulb and endoscopy and biopsy performed in patients with appropriate clinical and radiological findings.", "contents": "Transpyloric prolapse of polypoid gastric carcinoma. Four patients with discrete intraluminal filling defects in the duodenal bulb secondary to transpyloric prolapse of polypoid gastric carcinoma are reported. The lesions were pedunculated in 2 cases and sessile in the remaining 2. The clinical, radiological,and pathological findings are discussed. Prolapsed gastric carcinoma should be included in the differential diagnosis of localized intraluminal filling defects in the duodenal bulb and endoscopy and biopsy performed in patients with appropriate clinical and radiological findings."}
{"id": "PMID:192625", "title": "The influence of bacillary dysentery on the efficiency of oral poliovaccine in Egypt.", "content": "The rate of poliovirus excretion was found to be 64.6% in a group of 108 normal children and 11.95% in 184 diarrheal children. Diarrhea was due to Shigella in 70% of cases. This drew our attention to the presence of an etiologic relationship between the two findings, which may have a direct effect on the low efficiency of oral poliovaccine in our Country. Effect of Shigella infection on the take of oral poliovaccine was investigated in 14 normal and 10 children having acute diarrhea due to Shigella. Vaccine virus excretion was detected in 64.2% of normal children and only in 10% of diarrheal children. In vitro studies were done to determine the effect of killed Shigella suspensions or their endotoxin on the replication of poliovirus in tissue culture. Reduction of virus titre from 1-3 logs in the presence of killed Shigella or its endotoxin was observed. The sites of action and interfering factor (s) are discussed.", "contents": "The influence of bacillary dysentery on the efficiency of oral poliovaccine in Egypt. The rate of poliovirus excretion was found to be 64.6% in a group of 108 normal children and 11.95% in 184 diarrheal children. Diarrhea was due to Shigella in 70% of cases. This drew our attention to the presence of an etiologic relationship between the two findings, which may have a direct effect on the low efficiency of oral poliovaccine in our Country. Effect of Shigella infection on the take of oral poliovaccine was investigated in 14 normal and 10 children having acute diarrhea due to Shigella. Vaccine virus excretion was detected in 64.2% of normal children and only in 10% of diarrheal children. In vitro studies were done to determine the effect of killed Shigella suspensions or their endotoxin on the replication of poliovirus in tissue culture. Reduction of virus titre from 1-3 logs in the presence of killed Shigella or its endotoxin was observed. The sites of action and interfering factor (s) are discussed."}
{"id": "PMID:192629", "title": "[The excretion of chorionic gonadetropin in 55 cases of hydatidiform mole (author's transl)].", "content": "In 55 cases of hydatidiform mole, 323 quantitative assays of chorionic gonadotropin were evaluated. In cases of molar degeneration the mean HCG excretion was 20% below normal. In cases of hydatidiform mole and invasive mole the mean HCG excretion was significantly above normal. Many cases of hydatidiform mole and all cases of invasive mole showed a repeat rise of the HCG titres after curettage. The pattern of HCG excretion in hydatidiform mole is shown in diagrams.", "contents": "[The excretion of chorionic gonadetropin in 55 cases of hydatidiform mole (author's transl)]. In 55 cases of hydatidiform mole, 323 quantitative assays of chorionic gonadotropin were evaluated. In cases of molar degeneration the mean HCG excretion was 20% below normal. In cases of hydatidiform mole and invasive mole the mean HCG excretion was significantly above normal. Many cases of hydatidiform mole and all cases of invasive mole showed a repeat rise of the HCG titres after curettage. The pattern of HCG excretion in hydatidiform mole is shown in diagrams."}
{"id": "PMID:192634", "title": "Age-related alterations in membrane lipid and protein interactions: Arrhenius studies of microsomal glucose-6-phosphatase.", "content": "Arrhenius plots of glucose-6-phosphatase (EC 3.1.3.9) activity in liver microsomes from 6-month-old rats (young) showed discontinuities at 39, 30, 20 and 12 degrees C and change in activation energy at 20 degrees C. The enzyme activity in kidney microsomes of young rats showed essentially the same thermal discontinuities. In liver microsomes of 24-month-old rats (old) the enzyme showed discontinuities at 38, 30, 24 and 16 degrees C but not at 12 degrees C and the activation energy changed at 24 degrees C. In kidney microsomes of old rats discontinuities were seen at 38, 31, 22, 16 and 12 degrees C and the activation energy was constant from 0 to 41 degrees C. These results indicate that the interactions of membrane components are altered with age.", "contents": "Age-related alterations in membrane lipid and protein interactions: Arrhenius studies of microsomal glucose-6-phosphatase. Arrhenius plots of glucose-6-phosphatase (EC 3.1.3.9) activity in liver microsomes from 6-month-old rats (young) showed discontinuities at 39, 30, 20 and 12 degrees C and change in activation energy at 20 degrees C. The enzyme activity in kidney microsomes of young rats showed essentially the same thermal discontinuities. In liver microsomes of 24-month-old rats (old) the enzyme showed discontinuities at 38, 30, 24 and 16 degrees C but not at 12 degrees C and the activation energy changed at 24 degrees C. In kidney microsomes of old rats discontinuities were seen at 38, 31, 22, 16 and 12 degrees C and the activation energy was constant from 0 to 41 degrees C. These results indicate that the interactions of membrane components are altered with age."}
{"id": "PMID:192637", "title": "Transmission of rotavirus gastroenteritis from children to a monkey.", "content": "A pooled suspension of rotavirus was prepared from the stools of eight children with acute non-bacterial gastroenteritis. The suspension was infused into the duodenum and stomach of an infant monkey (Nemestrina macaque). Biopsy samples of duodenal mucosa were taken at several intervals after inoculation, examined by light and electron microscopy, and assayed for lysosomal activity. Virus-like particles were seen within and around microvilli and intracellularly within vesicles as early as 20 minutes after the infusion. On the fourth and fifth days, large lysosomal bodies containing numerous virus-like particles were found within epithelial cells of the duodenal villi. No such particles were seen in the pre-inoculation sample or at days 16 or 25 after infection. The present study would appear to be the first demonstration of the transmission of this human virus to another species.", "contents": "Transmission of rotavirus gastroenteritis from children to a monkey. A pooled suspension of rotavirus was prepared from the stools of eight children with acute non-bacterial gastroenteritis. The suspension was infused into the duodenum and stomach of an infant monkey (Nemestrina macaque). Biopsy samples of duodenal mucosa were taken at several intervals after inoculation, examined by light and electron microscopy, and assayed for lysosomal activity. Virus-like particles were seen within and around microvilli and intracellularly within vesicles as early as 20 minutes after the infusion. On the fourth and fifth days, large lysosomal bodies containing numerous virus-like particles were found within epithelial cells of the duodenal villi. No such particles were seen in the pre-inoculation sample or at days 16 or 25 after infection. The present study would appear to be the first demonstration of the transmission of this human virus to another species."}
{"id": "PMID:192640", "title": "Certain aspects of the use of new method of microscopy in oncology.", "content": "Electron microscopic studies on human neoplasms demonstrated that the typical cells fo individual neoplasms retain the ability of showing their specific ultrastructural differentiation. This fact provides theoretical basis for the use of electron microscopy in oncological practice for purposes of differential diagnosis. It also allows rejection of the concept of \"dedifferentiation\" and ultrastructural \"simplification\" as main ways of formation of neoplastic cells.", "contents": "Certain aspects of the use of new method of microscopy in oncology. Electron microscopic studies on human neoplasms demonstrated that the typical cells fo individual neoplasms retain the ability of showing their specific ultrastructural differentiation. This fact provides theoretical basis for the use of electron microscopy in oncological practice for purposes of differential diagnosis. It also allows rejection of the concept of \"dedifferentiation\" and ultrastructural \"simplification\" as main ways of formation of neoplastic cells."}
{"id": "PMID:192641", "title": "Ultrastructural localization of enzymes of the membranes and RNP-structures of the nuclei of normal and neoplastic cells.", "content": "Ultrastructural localization of some oxidative and dephosphorylating enzymes was investigated in isolated rat and mouse liver nuclei and in nuclei isolated from various rat hepatomas. In the discussion the significance of changes in the activity of these enzymes in neoplastic cells is considered.", "contents": "Ultrastructural localization of enzymes of the membranes and RNP-structures of the nuclei of normal and neoplastic cells. Ultrastructural localization of some oxidative and dephosphorylating enzymes was investigated in isolated rat and mouse liver nuclei and in nuclei isolated from various rat hepatomas. In the discussion the significance of changes in the activity of these enzymes in neoplastic cells is considered."}
{"id": "PMID:192642", "title": "Hydrolysis of nucleoside triphosphate in plasma membranes of the hepatocytes of normal, regenerating and foetal livers and in cancer cells of hepatomas.", "content": "Electron histochemical studies show that changes in the nucleoside triphosphatase activity in plasma membranes of cancer cells can proceed in different directions. Some cells show a high activity of magnesium-dependent NTPase over the whole membrane surface (perimeter), while others have a low enzymic activity which is present only in certain  regions of the membranes, the remaining cells possessing no enzyme activity at all. These changes are not strictly characteristic of cancer cells alone.", "contents": "Hydrolysis of nucleoside triphosphate in plasma membranes of the hepatocytes of normal, regenerating and foetal livers and in cancer cells of hepatomas. Electron histochemical studies show that changes in the nucleoside triphosphatase activity in plasma membranes of cancer cells can proceed in different directions. Some cells show a high activity of magnesium-dependent NTPase over the whole membrane surface (perimeter), while others have a low enzymic activity which is present only in certain  regions of the membranes, the remaining cells possessing no enzyme activity at all. These changes are not strictly characteristic of cancer cells alone."}
{"id": "PMID:192643", "title": "Histochemical methods in the diagnosis of precancerous states and early forms of cancer of the uterine cervix.", "content": "Histochemical characteristics of displasia, various forms of the cancer in situ and initial invasive cancer together with histochemical criteria for differential diagnoses of these processes are given.", "contents": "Histochemical methods in the diagnosis of precancerous states and early forms of cancer of the uterine cervix. Histochemical characteristics of displasia, various forms of the cancer in situ and initial invasive cancer together with histochemical criteria for differential diagnoses of these processes are given."}
{"id": "PMID:192644", "title": "Ultrastructural localization of cytoplasmic phosphatases in preimplantation mouse embryos.", "content": "The appearance and localization of the cytoplasmic phosphatases [acid phosphatase (AcPase) as a marker of lysosomes, TPPase as a marker of the Golgi apparatus, and NDPase (IDPase) as enzymatic marker of the endoplasmic reticulum (ER)] were cytochemically studied on the ultrastructural level in secondary oocytes and in preimplantation mouse embryos. The detectable AcPase activity, located on the inner surface of the membrane delimiting some cytoplasmic vacuoles (lysosomes and autophagic vacuoles), appears at the eight-cell stage and grows pregressively stronger up to the blastocyst stage. Golgi-associated reaction for TPPase was detectable in oocytes, dropped in one-cell embryos and became negative in the two-cell embryos. The reaction for TPPase and IDPase was present in plasma membranes of oocytes and early embryos and appeared in the delimiting membrane of some cytoplasmic vesicles in eight-cell embryos. Some activity of IDPase was found in small segments of the ER at the morula and blastocyst stage. The observed results suggest that the lysosomes are the first organelles in early embryos showing activity of the marker enzymes of the phosphatase type, while the activity of other marker enzymes is mainly concentrated in the plasma membrane of blastomeres. It cannot be excluded, however, that positive reaction for TPPase and IDPase in the plasma membrane results from nonspecific action of other phosphatases.", "contents": "Ultrastructural localization of cytoplasmic phosphatases in preimplantation mouse embryos. The appearance and localization of the cytoplasmic phosphatases [acid phosphatase (AcPase) as a marker of lysosomes, TPPase as a marker of the Golgi apparatus, and NDPase (IDPase) as enzymatic marker of the endoplasmic reticulum (ER)] were cytochemically studied on the ultrastructural level in secondary oocytes and in preimplantation mouse embryos. The detectable AcPase activity, located on the inner surface of the membrane delimiting some cytoplasmic vacuoles (lysosomes and autophagic vacuoles), appears at the eight-cell stage and grows pregressively stronger up to the blastocyst stage. Golgi-associated reaction for TPPase was detectable in oocytes, dropped in one-cell embryos and became negative in the two-cell embryos. The reaction for TPPase and IDPase was present in plasma membranes of oocytes and early embryos and appeared in the delimiting membrane of some cytoplasmic vesicles in eight-cell embryos. Some activity of IDPase was found in small segments of the ER at the morula and blastocyst stage. The observed results suggest that the lysosomes are the first organelles in early embryos showing activity of the marker enzymes of the phosphatase type, while the activity of other marker enzymes is mainly concentrated in the plasma membrane of blastomeres. It cannot be excluded, however, that positive reaction for TPPase and IDPase in the plasma membrane results from nonspecific action of other phosphatases."}
{"id": "PMID:192645", "title": "Activities of oxidative enzymes in thyroid follicles of Xiphophorin fishes.", "content": "The activity of some intracellular oxidative enzymes was studied histochemically in the cells of the thyroid follicles of teleost fishes of the genus Xiphophorus. The experimental material consisted of animals of the red swordtail and Mexican swordtail breeds of Xiphophorus helleri and of melanotic Xiphophorus maculatus fishes. Observations were carried out on adult specimens of both sexes, including pregnant femals of Mexican swordtail. Moreover, immature Mexican swordtails of both sexes were examined. Thyroid follicles were found to be present in the subpharyngeal region of all fishes studied. The distribution of these follicles as well as their number and form depended on sex, age and on the analysed stage of prenancy. A smaller number and size of thyroid follicles were characteristic of immature specimens, whereas they were most numerous in the thyroids of pregnant fishes. The follicles were arranged in characteristic dense aggregations, especially in the melanotic platyfish. The follicular eipthelium in the fishes under study was usually cubical, but pregnant and non-pregnant adult females also contained a considerable number of larger follicles with flattened epithelium. Besides, thyroid follicles of multilayer epithelium were rather frequently encountered, especially in male fishes, irrespective of their age. The thyroid follicle cells of these fishes demonstrated invariably high activities of reduced NAD and NADP dehydrogenases and of beta-hydroxybutyrate dehydrogenase, and a low activity of succinat dehydrogenase. The intensities of alpha-glycerophosphate and lactate dehydrogenases and of cytochrome oxidase varied with sex, age and breed of the studied fishes. The immature and pregnant fishes showed the most clearly pronounced differences in the intensity of enzymic activity, the thyroid follicles of immature specimens revealing a high activity of lactate dehydrogenase and low activity of cytochrome oxidase, an inverse picture being seen in pregnant fishes. The adult forms of both sexes exhibited an enhanced activity of cytochrome oxidase and a decline in that of lactate dehydrogenase. The observed differences in the intensities of enzymic acitivities in the thyroids of the studied fishes are related with functions of this gland which in the period of growth are different from those in the period of sexual maturity, and certainly also with individual metabolic characteristics of the studied fishes.", "contents": "Activities of oxidative enzymes in thyroid follicles of Xiphophorin fishes. The activity of some intracellular oxidative enzymes was studied histochemically in the cells of the thyroid follicles of teleost fishes of the genus Xiphophorus. The experimental material consisted of animals of the red swordtail and Mexican swordtail breeds of Xiphophorus helleri and of melanotic Xiphophorus maculatus fishes. Observations were carried out on adult specimens of both sexes, including pregnant femals of Mexican swordtail. Moreover, immature Mexican swordtails of both sexes were examined. Thyroid follicles were found to be present in the subpharyngeal region of all fishes studied. The distribution of these follicles as well as their number and form depended on sex, age and on the analysed stage of prenancy. A smaller number and size of thyroid follicles were characteristic of immature specimens, whereas they were most numerous in the thyroids of pregnant fishes. The follicles were arranged in characteristic dense aggregations, especially in the melanotic platyfish. The follicular eipthelium in the fishes under study was usually cubical, but pregnant and non-pregnant adult females also contained a considerable number of larger follicles with flattened epithelium. Besides, thyroid follicles of multilayer epithelium were rather frequently encountered, especially in male fishes, irrespective of their age. The thyroid follicle cells of these fishes demonstrated invariably high activities of reduced NAD and NADP dehydrogenases and of beta-hydroxybutyrate dehydrogenase, and a low activity of succinat dehydrogenase. The intensities of alpha-glycerophosphate and lactate dehydrogenases and of cytochrome oxidase varied with sex, age and breed of the studied fishes. The immature and pregnant fishes showed the most clearly pronounced differences in the intensity of enzymic activity, the thyroid follicles of immature specimens revealing a high activity of lactate dehydrogenase and low activity of cytochrome oxidase, an inverse picture being seen in pregnant fishes. The adult forms of both sexes exhibited an enhanced activity of cytochrome oxidase and a decline in that of lactate dehydrogenase. The observed differences in the intensities of enzymic acitivities in the thyroids of the studied fishes are related with functions of this gland which in the period of growth are different from those in the period of sexual maturity, and certainly also with individual metabolic characteristics of the studied fishes."}
{"id": "PMID:192646", "title": "The ammocoetes endostyle: its oxidative enzymes as an evidence of its homology with the thyroid of higher chordates.", "content": "Histochemical methods were used for the demonstration of activity of the following intracellular oxidative enzymes, unstudied hitherto, in the epithelial cells of the endostyle of the river lampre (Lampertr aluviatilis L.) ammocoetes: reduced NAD dehydrogenase (NADD), lactate dehydrogenase (LD), cytochrome oxidase (CO), succinate dehydrogenase (SD), alpha-glycerophosphate dehydrogenase (alphaGPD) and glucose-6-phosphate dehydrogenase (G6PD). The activities of NADD and LD in the iodophil and throidogenic cells of type 3, then of subtype 2c and partly types 4 and 5 of the endostylar epithelium and the hypobranchial duct-lining epithelium were particularly ithe larva proves the possibility of their participation in the formation of the thyroid gland in the period of metamorphosis. In type 1 cells of the ammocoetes, despite their fairly strong enzymatic reactivity, the oxidative activity does not change significantly during the ontogenetic stages examined. The data obtained make it possible to modify the present views on the genesis of the thyroid gland of the adult  lamprey, namely, they indicate the participation of the type 6 cells of the hypobranchial duct-lining epithelium in the process of thyroidogenesis.", "contents": "The ammocoetes endostyle: its oxidative enzymes as an evidence of its homology with the thyroid of higher chordates. Histochemical methods were used for the demonstration of activity of the following intracellular oxidative enzymes, unstudied hitherto, in the epithelial cells of the endostyle of the river lampre (Lampertr aluviatilis L.) ammocoetes: reduced NAD dehydrogenase (NADD), lactate dehydrogenase (LD), cytochrome oxidase (CO), succinate dehydrogenase (SD), alpha-glycerophosphate dehydrogenase (alphaGPD) and glucose-6-phosphate dehydrogenase (G6PD). The activities of NADD and LD in the iodophil and throidogenic cells of type 3, then of subtype 2c and partly types 4 and 5 of the endostylar epithelium and the hypobranchial duct-lining epithelium were particularly ithe larva proves the possibility of their participation in the formation of the thyroid gland in the period of metamorphosis. In type 1 cells of the ammocoetes, despite their fairly strong enzymatic reactivity, the oxidative activity does not change significantly during the ontogenetic stages examined. The data obtained make it possible to modify the present views on the genesis of the thyroid gland of the adult  lamprey, namely, they indicate the participation of the type 6 cells of the hypobranchial duct-lining epithelium in the process of thyroidogenesis."}
{"id": "PMID:192650", "title": "[The angiographic picture of arteriovenous fistulae (author's transl)].", "content": "The angiographic appearances and the significance of various angiographic signs are discussed in relation to 12 arteriovenous fistulae demonstrated angiographically in 11 patients. Dilatation of the supplying artery is an indication of the size of the shunt and is particularly prominent in the presence of multiple, congenital microfistulae. The technique developed in our clinic for investigating suspected or known A-V fistulae is described. This technique simplifies the differential diagnosis between the Klippel-Tr\u00e9naunay syndrome and the prognostically less favourable Weber syndrome.", "contents": "[The angiographic picture of arteriovenous fistulae (author's transl)]. The angiographic appearances and the significance of various angiographic signs are discussed in relation to 12 arteriovenous fistulae demonstrated angiographically in 11 patients. Dilatation of the supplying artery is an indication of the size of the shunt and is particularly prominent in the presence of multiple, congenital microfistulae. The technique developed in our clinic for investigating suspected or known A-V fistulae is described. This technique simplifies the differential diagnosis between the Klippel-Tr\u00e9naunay syndrome and the prognostically less favourable Weber syndrome."}
{"id": "PMID:192651", "title": "[Polyneuropathies as a diagnostic and therapeutic task].", "content": "Despite their variety the syndromes of peripheral neuropathy are variations of just one subject. The most different lesions might be their cause. Therefore, one should not be satisfied with the diagnosis peripheral neuropathy, but should always try to clarify the etiology. Form and extension of the disturbances give essential hints. As far as possible, therapy should be directed against the respective causes. For several types of neuropathy prevention is possible. Symptomatic treatment is also important and in many cases even essential for survival.", "contents": "[Polyneuropathies as a diagnostic and therapeutic task]. Despite their variety the syndromes of peripheral neuropathy are variations of just one subject. The most different lesions might be their cause. Therefore, one should not be satisfied with the diagnosis peripheral neuropathy, but should always try to clarify the etiology. Form and extension of the disturbances give essential hints. As far as possible, therapy should be directed against the respective causes. For several types of neuropathy prevention is possible. Symptomatic treatment is also important and in many cases even essential for survival."}
{"id": "PMID:192652", "title": "[Chemodectoma in the carotid triangle region].", "content": "The only treatment of the extensive and infiltrative carotid body tumors is radical resection. Exact preoperative diagnosis in unknown tumors of the neck avoid hazardous complications during operative resection. This report contains diagnosis and definition of these rare tumors. Various operative procedures of tumor-resection are discussed. Carotid angiographies and operative photographs from three cases demonstrate the extent and close relation of the carotid artery.", "contents": "[Chemodectoma in the carotid triangle region]. The only treatment of the extensive and infiltrative carotid body tumors is radical resection. Exact preoperative diagnosis in unknown tumors of the neck avoid hazardous complications during operative resection. This report contains diagnosis and definition of these rare tumors. Various operative procedures of tumor-resection are discussed. Carotid angiographies and operative photographs from three cases demonstrate the extent and close relation of the carotid artery."}
{"id": "PMID:192653", "title": "[Prevention and therapy of viral diseases with special reference to interferon].", "content": "Human leukocyte interferon (HLI) was used for treatment of human diploid fibroblasts before and after infection with vaccinia virus, herpes simplex virus type 1 (HSV 1), herpes simplex virus type 2 (HSV 2), and varicella zoster virus (VZV). Vero cells were infected with Medical Lake macaque herpes virus (MLMV), and treated with HLI in the same way. In all of these systems HLI exhibited an antiviral effect when administered before infection, and this effect could be increased by additional HLI treatment after infection. In vivo studies with HLI treatment were performed in monkeys experimentally infected with vaccinia virus, HSV 1, and MLMV. Vaccinia and herpes keratitis were prevented by local, prophylactic administration of HLI. Generalized infections with vaccinia virus and MLMV in monkeys immunosuppressed by antilymphocyte globulin, were significantly modified by either prophylactic or therapeutic systemic treatment with HLI.", "contents": "[Prevention and therapy of viral diseases with special reference to interferon]. Human leukocyte interferon (HLI) was used for treatment of human diploid fibroblasts before and after infection with vaccinia virus, herpes simplex virus type 1 (HSV 1), herpes simplex virus type 2 (HSV 2), and varicella zoster virus (VZV). Vero cells were infected with Medical Lake macaque herpes virus (MLMV), and treated with HLI in the same way. In all of these systems HLI exhibited an antiviral effect when administered before infection, and this effect could be increased by additional HLI treatment after infection. In vivo studies with HLI treatment were performed in monkeys experimentally infected with vaccinia virus, HSV 1, and MLMV. Vaccinia and herpes keratitis were prevented by local, prophylactic administration of HLI. Generalized infections with vaccinia virus and MLMV in monkeys immunosuppressed by antilymphocyte globulin, were significantly modified by either prophylactic or therapeutic systemic treatment with HLI."}
{"id": "PMID:192654", "title": "Localization of chymotrypsin-like cationic protein, collagenase and elastase in azurophil granules of human neutrophilic polymorphonuclear leukocytes.", "content": "The subcellular localization of granulocyte collagenase, elastase and chymotrypsin-like cationic protein was determined using velocity centrifugation of cytoplasmic granules of human polymorphonuclear leukocytes. The proteases were assayed by immunochemical and enzymatic methods. Measurements of lactoferrin and myeloperoxidase distinguish exactly between constituents of specific and azurophil granules. Collagenase, elastase and chymotrypsin-like cationic proteins showed an almost identical sharp and unimodal distribution. They co-sedimented with myeloperoxidase demonstrating that these enzymes are localized exclusively in the azurophil granules.", "contents": "Localization of chymotrypsin-like cationic protein, collagenase and elastase in azurophil granules of human neutrophilic polymorphonuclear leukocytes. The subcellular localization of granulocyte collagenase, elastase and chymotrypsin-like cationic protein was determined using velocity centrifugation of cytoplasmic granules of human polymorphonuclear leukocytes. The proteases were assayed by immunochemical and enzymatic methods. Measurements of lactoferrin and myeloperoxidase distinguish exactly between constituents of specific and azurophil granules. Collagenase, elastase and chymotrypsin-like cationic proteins showed an almost identical sharp and unimodal distribution. They co-sedimented with myeloperoxidase demonstrating that these enzymes are localized exclusively in the azurophil granules."}
{"id": "PMID:192656", "title": "Patients released after Wyatt: where did they go?", "content": "The author investigated the posthospital outcome of a random sample of 228 patients released from Bryce Hospital between June 1972 and June 1973. Approximately 72% of the ex-patients participating in the follow-up study had been released from the hospital to a household containing a member of the family. At the time of the follow-up interviews, conducted between May 1975 and June 1976, approximately 63% of the ex-patients were found to be living in non-institutional settings. The study also found that a majority of the patients had not been readmitted to a state psychiatric facility since their release.", "contents": "Patients released after Wyatt: where did they go? The author investigated the posthospital outcome of a random sample of 228 patients released from Bryce Hospital between June 1972 and June 1973. Approximately 72% of the ex-patients participating in the follow-up study had been released from the hospital to a household containing a member of the family. At the time of the follow-up interviews, conducted between May 1975 and June 1976, approximately 63% of the ex-patients were found to be living in non-institutional settings. The study also found that a majority of the patients had not been readmitted to a state psychiatric facility since their release."}
{"id": "PMID:192657", "title": "Myofibroblasts and related cells in malignant fibrous and fibrohistiocytic tumors.", "content": "Myofibroblasts were detected by electron microscopy in five of five cases of fibrosarcoma and in five of six cases of malignant fibrous histiocytoma. In some areas myofibroblasts constituted up to 75 per cent of the tumor cells. Most myofibroblasts contained only sheaves of myofilaments along the margins of the cells, but some cells contained larger bundles of myofilaments and very closely resembled smooth muscle cells. An additional related type of cell was seen in several cases; it was large and possessed abundant eosinophilic cytoplasm, resembling a rhabdomyoblast at the light microscopic level. By electron microscopy this type of cell was seen to contain plentiful rough endoplasmic reticulum and large aggregates of fine filaments with rare dense bodies. These findings suggest that fibrosarcomas and malignant fibrous histiocytomas contain cells showing a spectrum of differentiation from fibrocytic to myogenic and that at the ultrastructural level the distinction between fibroblast and smooth muscle tumors may be blurred.", "contents": "Myofibroblasts and related cells in malignant fibrous and fibrohistiocytic tumors. Myofibroblasts were detected by electron microscopy in five of five cases of fibrosarcoma and in five of six cases of malignant fibrous histiocytoma. In some areas myofibroblasts constituted up to 75 per cent of the tumor cells. Most myofibroblasts contained only sheaves of myofilaments along the margins of the cells, but some cells contained larger bundles of myofilaments and very closely resembled smooth muscle cells. An additional related type of cell was seen in several cases; it was large and possessed abundant eosinophilic cytoplasm, resembling a rhabdomyoblast at the light microscopic level. By electron microscopy this type of cell was seen to contain plentiful rough endoplasmic reticulum and large aggregates of fine filaments with rare dense bodies. These findings suggest that fibrosarcomas and malignant fibrous histiocytomas contain cells showing a spectrum of differentiation from fibrocytic to myogenic and that at the ultrastructural level the distinction between fibroblast and smooth muscle tumors may be blurred."}
{"id": "PMID:192658", "title": "Morphologic aspects of nuclear bodies in a case of bronchiolar-alveolar carcinoma of the lung.", "content": "The ultrastructural features of a bronchiolar-alveolar carcinoma of the lung are described wherein the presence of nuclear bodies in many of the tumor cells were noted. Although these bodies are not viral elements, it is surmised that they may be virus associated and consequently possibly related to the etiology of this tumor. A review of the ultrastructural findings in the pulmonary adenomatosis of sheep is presented, and these are compared with those in human disease. Experimental evidence of an infectious agent responsible for human lung carcinomas is discussed, and possible avenues for future investigation are delineated.", "contents": "Morphologic aspects of nuclear bodies in a case of bronchiolar-alveolar carcinoma of the lung. The ultrastructural features of a bronchiolar-alveolar carcinoma of the lung are described wherein the presence of nuclear bodies in many of the tumor cells were noted. Although these bodies are not viral elements, it is surmised that they may be virus associated and consequently possibly related to the etiology of this tumor. A review of the ultrastructural findings in the pulmonary adenomatosis of sheep is presented, and these are compared with those in human disease. Experimental evidence of an infectious agent responsible for human lung carcinomas is discussed, and possible avenues for future investigation are delineated."}
{"id": "PMID:192659", "title": "Benign hepatic lesions and orally administered contraceptives. A report of seven cases and a critical analysis of the literature.", "content": "A consecutive series of 12 benign hepatic lesions in women consisted of six cases of focal nodular hyperplasia and six cases of liver cell adenoma. Five of the six women with liver cell adenoma and two of the six with focal nodular hyperplasia had taken orally active contraceptive hormones. These few cases reflect a similar impression gained from a critical analysis of the literature, namely, that focal nodular hyperplasia may be unrelated to the oral administration of contraceptive hormones, whereas the increase in liver cell adenoma reported in recent years is probably related to such therapy. Two women with liver cell adenomas were asymptomatic six and four years after incomplete resection of the tumor. These are the longest intervals thus far reported for uncomplicated survival in incompletely resected liver cell adenoma.", "contents": "Benign hepatic lesions and orally administered contraceptives. A report of seven cases and a critical analysis of the literature. A consecutive series of 12 benign hepatic lesions in women consisted of six cases of focal nodular hyperplasia and six cases of liver cell adenoma. Five of the six women with liver cell adenoma and two of the six with focal nodular hyperplasia had taken orally active contraceptive hormones. These few cases reflect a similar impression gained from a critical analysis of the literature, namely, that focal nodular hyperplasia may be unrelated to the oral administration of contraceptive hormones, whereas the increase in liver cell adenoma reported in recent years is probably related to such therapy. Two women with liver cell adenomas were asymptomatic six and four years after incomplete resection of the tumor. These are the longest intervals thus far reported for uncomplicated survival in incompletely resected liver cell adenoma."}
{"id": "PMID:192660", "title": "Cytomegalovirus oophoritis: ovarian cortical necrosis.", "content": "Three of eight female patients with cytomegalovirus disease had evidence of ovarian infection at autopsy. All three patients with ovarian lesions were postmenopausal; the remaining five were premenopausal. The lesions, which may be bilateral and may occur without evidence of cytomegalovirus infection elsewhere, are distinctive macroscopically, pathognomonic microscopically, and characterized by acute focal ovarian cortical necrosis with numerous cytomegalic cells and a variable but usually severe inflammatory reaction. It is suggested that reduced ovarian cortical vascular perfusion reactivates a latent infection in cortical stromal cells. This elicits inflammatory necrosis and the characteristic morphological lesions. This previously unreported lesion is not likely to have clinical importance.", "contents": "Cytomegalovirus oophoritis: ovarian cortical necrosis. Three of eight female patients with cytomegalovirus disease had evidence of ovarian infection at autopsy. All three patients with ovarian lesions were postmenopausal; the remaining five were premenopausal. The lesions, which may be bilateral and may occur without evidence of cytomegalovirus infection elsewhere, are distinctive macroscopically, pathognomonic microscopically, and characterized by acute focal ovarian cortical necrosis with numerous cytomegalic cells and a variable but usually severe inflammatory reaction. It is suggested that reduced ovarian cortical vascular perfusion reactivates a latent infection in cortical stromal cells. This elicits inflammatory necrosis and the characteristic morphological lesions. This previously unreported lesion is not likely to have clinical importance."}
{"id": "PMID:192661", "title": "Red cell adenylate kinase phenotypes in the affective disorders.", "content": "The red cell adenylate kinase (AK) phenotype was determined by starch gel electrophoresis in 96 adult Caucasian subjects with affective disorders (24 with bipolar illness and 72 with unipolar illness). The phenotype frequencies and the gene frequencies of the bipolar group closely resembled that of the control subjects (180 subjects drawn from the population of a large institution for the mentally retarded), the unipolar group however, showed a significant increase in the frequency of the AK2 allele. The significance of these results have been discussed in relation to the known genetic and biochemical findings in the affective disorders. It is suggested that the mechanism involved may be a reduction of the enzyme activity in the tissues of subjects with the AK 2:1 phenotype. This may present a selective disadvantage in the form of a decrease in control of energy metabolism in general, and control of adenine nucleotide levels in nervous tissue in particular.", "contents": "Red cell adenylate kinase phenotypes in the affective disorders. The red cell adenylate kinase (AK) phenotype was determined by starch gel electrophoresis in 96 adult Caucasian subjects with affective disorders (24 with bipolar illness and 72 with unipolar illness). The phenotype frequencies and the gene frequencies of the bipolar group closely resembled that of the control subjects (180 subjects drawn from the population of a large institution for the mentally retarded), the unipolar group however, showed a significant increase in the frequency of the AK2 allele. The significance of these results have been discussed in relation to the known genetic and biochemical findings in the affective disorders. It is suggested that the mechanism involved may be a reduction of the enzyme activity in the tissues of subjects with the AK 2:1 phenotype. This may present a selective disadvantage in the form of a decrease in control of energy metabolism in general, and control of adenine nucleotide levels in nervous tissue in particular."}
{"id": "PMID:192663", "title": "Isolation of cell lines from embryos of the cockroach, Blattella germanica.", "content": "Cell lines were isolated from three stages of embryos of Blattella germanica dissociated with trypsin. The lines have been subcultured 50 to 134 times in 3 years. Line UM-BGE-1 was isolated from germ band embryos at stages of segmentation and limb-bud formation (5 days old). Line UM-BGE-2 was derived from embryos at dorsal closure (7 days old). Line UM-BGE-4 arose from embryos in the germ band and dorsal closure stages (5 and 7 days old): these cells colonize as hollow spheres or vesicles. Line UM-BGE-5, isolated during organogenesis (10 days old), developed into two distinct sublines. Subline alpha is composed of round cells that do not attach to the flask. Subline beta grows as an attached monolayer; the cells can be removed with a saline solution containing 20 mM disodium dihydrogen Versenate. Most of the cells of these lines have the diploid chromosome number (23 or 24) excepting line UM-BGE-1 in which the tetraploid number predominates", "contents": "Isolation of cell lines from embryos of the cockroach, Blattella germanica. Cell lines were isolated from three stages of embryos of Blattella germanica dissociated with trypsin. The lines have been subcultured 50 to 134 times in 3 years. Line UM-BGE-1 was isolated from germ band embryos at stages of segmentation and limb-bud formation (5 days old). Line UM-BGE-2 was derived from embryos at dorsal closure (7 days old). Line UM-BGE-4 arose from embryos in the germ band and dorsal closure stages (5 and 7 days old): these cells colonize as hollow spheres or vesicles. Line UM-BGE-5, isolated during organogenesis (10 days old), developed into two distinct sublines. Subline alpha is composed of round cells that do not attach to the flask. Subline beta grows as an attached monolayer; the cells can be removed with a saline solution containing 20 mM disodium dihydrogen Versenate. Most of the cells of these lines have the diploid chromosome number (23 or 24) excepting line UM-BGE-1 in which the tetraploid number predominates"}
{"id": "PMID:192664", "title": "Cyclic AMP and serum arrest of the mitotic activity of human diploid fibroblasts.", "content": "Mitotic activity in confluent cultures of human diploid fibroblasts was arrested by the reduction of the serum concentration of the incubation medium to 0.5% or by the addition of 0.5 mM 6-N, 2'-O-dibutyryl-adenosine 3':5'-cyclic monophosphate (db cAMP). Under either of these conditions, cultures maintained a constant cell number for 14 days; cultures continuously exposed to medium containing 10% serum doubled their cell number during this 14-day period. The protein cotent per cell decreased by 20% when cells were maintained with 0.5% serum whereas that of cells exposed to db cAMP remained constant. Ultrastructural studies revealed that cells exposed to db cAMP exhibited a morphology typical of cells cultures with 10% serum alone, whereas cells incubated with 0.5% serum showed the ultrastructural changes in mitochondria, endoplasmic reticulum and Golgi complex previously identified with low-serum arrest. Cellular adenosine 3':5'-cyclic monophosphate (cAMP) levels remained constant during the 7-day growth period in which confluency was attained, as well as during the 14-day arrested period with 0.5% serum. These results indicated that the mitotic inhibition induced by reducing the serum concentration of the incubation medium was not mediated by increased intracellular levels of cAMP and differed from that induced by the addition of exogenous db cAMP.", "contents": "Cyclic AMP and serum arrest of the mitotic activity of human diploid fibroblasts. Mitotic activity in confluent cultures of human diploid fibroblasts was arrested by the reduction of the serum concentration of the incubation medium to 0.5% or by the addition of 0.5 mM 6-N, 2'-O-dibutyryl-adenosine 3':5'-cyclic monophosphate (db cAMP). Under either of these conditions, cultures maintained a constant cell number for 14 days; cultures continuously exposed to medium containing 10% serum doubled their cell number during this 14-day period. The protein cotent per cell decreased by 20% when cells were maintained with 0.5% serum whereas that of cells exposed to db cAMP remained constant. Ultrastructural studies revealed that cells exposed to db cAMP exhibited a morphology typical of cells cultures with 10% serum alone, whereas cells incubated with 0.5% serum showed the ultrastructural changes in mitochondria, endoplasmic reticulum and Golgi complex previously identified with low-serum arrest. Cellular adenosine 3':5'-cyclic monophosphate (cAMP) levels remained constant during the 7-day growth period in which confluency was attained, as well as during the 14-day arrested period with 0.5% serum. These results indicated that the mitotic inhibition induced by reducing the serum concentration of the incubation medium was not mediated by increased intracellular levels of cAMP and differed from that induced by the addition of exogenous db cAMP."}
{"id": "PMID:192668", "title": "Cholera toxin, ganglioside receptors and the immune response.", "content": "Cholera toxin activates plasma membrane adenylate cyclase in all mammalian cell types. The structure-function relationship of the toxin has recently been clarified, and the cell membrane receptor identified. This information has made cholera toxin the \"agent of choice\" for studies in many biological systems of the possible regulatory role of adenylate cyclase/cyclic AMP. This article describes briefly our current knowledge about the toxin and its receptor. It then reviews recent research which has revealed that cholera toxin has strong modulating influences on the proliferation of normal and malignant lympocytes as well as on the initiation and expression of immune responses. The toxin has been found to inhibit DNA synthesis of B and T lymphocytes in vitro without inducing cell death and also to inhibit seems to decrease antibody secretion from plasma cells in vitro, and might also interfere with the release of other soluble immunological mediator subtances. In vivo cholera toxin induces a transient involution of the spleen and a more prolonged lymphocyte depletion of the thymus in mice; these effects appear to be mediated through the adrenal glands. The toxin inhibitors allograft rejection, and either stimulates or suppresses antibody formation depending on the timing of the toxin in relation to the antigen administration. It increases the capacity of the spleen cells to induce graft-vs-host reactions and the \"allogeneic effect\" on antibody production. An inhibitory effect on a normal suppressor population among the spleen cells has been identified. The findings illustrate the complex effects induced on the immune system by the probably most discriminative investigative tool available for stimulation of the adenylate cyclase/cyclic AMP system.", "contents": "Cholera toxin, ganglioside receptors and the immune response. Cholera toxin activates plasma membrane adenylate cyclase in all mammalian cell types. The structure-function relationship of the toxin has recently been clarified, and the cell membrane receptor identified. This information has made cholera toxin the \"agent of choice\" for studies in many biological systems of the possible regulatory role of adenylate cyclase/cyclic AMP. This article describes briefly our current knowledge about the toxin and its receptor. It then reviews recent research which has revealed that cholera toxin has strong modulating influences on the proliferation of normal and malignant lympocytes as well as on the initiation and expression of immune responses. The toxin has been found to inhibit DNA synthesis of B and T lymphocytes in vitro without inducing cell death and also to inhibit seems to decrease antibody secretion from plasma cells in vitro, and might also interfere with the release of other soluble immunological mediator subtances. In vivo cholera toxin induces a transient involution of the spleen and a more prolonged lymphocyte depletion of the thymus in mice; these effects appear to be mediated through the adrenal glands. The toxin inhibitors allograft rejection, and either stimulates or suppresses antibody formation depending on the timing of the toxin in relation to the antigen administration. It increases the capacity of the spleen cells to induce graft-vs-host reactions and the \"allogeneic effect\" on antibody production. An inhibitory effect on a normal suppressor population among the spleen cells has been identified. The findings illustrate the complex effects induced on the immune system by the probably most discriminative investigative tool available for stimulation of the adenylate cyclase/cyclic AMP system."}
{"id": "PMID:192671", "title": "Role of macrophages in hepatitis induced by Herpes simplex virus types 1 and 2 in mice.", "content": "A marked difference was found between herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in the induction of hepatic necrotic lesions in mice inoculated intraperitoneally. Although HSV-2 produced many large, progressive liver lesions in 4-week-old BALB/c mice, HSV-1 only occasionally induced a few, self-limiting foci, which eventually healed. This was reflected in the isolation of HSV from the liver and spleen, two organs that are rich in macrophages. Although HSV-1 could be only temporarily isolated, HSV-2 was found in the two organs until the mice died. On the other hand, no such difference was found in the isolation of virus from the brain, which contains no macrophages, and the mice eventually died from encephalitis. This difference in hepatic involvement caused by the two virus types was found to parallel a marked difference in the restriction of HSV-1 and HSV-2 replication by macrophages as measured by an infectious center assay in vitro. HSV-2 produced 17 times as many infectious centers in infected peritoneal macrophage cultures as did HSV-1. Furthermore, the HSV-2 plaques in the cell overlay were large and increasing in size, whereas the HSV-1 plaques were small and showed regression on prolonged incubation. It was shown that this diversity was unique to the macrophage population and not caused by differences in the uptake of virus by macrophages. This model involving two closely related virus types shows the importance of tissue macrophages in the primary host defense against virus infections.", "contents": "Role of macrophages in hepatitis induced by Herpes simplex virus types 1 and 2 in mice. A marked difference was found between herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in the induction of hepatic necrotic lesions in mice inoculated intraperitoneally. Although HSV-2 produced many large, progressive liver lesions in 4-week-old BALB/c mice, HSV-1 only occasionally induced a few, self-limiting foci, which eventually healed. This was reflected in the isolation of HSV from the liver and spleen, two organs that are rich in macrophages. Although HSV-1 could be only temporarily isolated, HSV-2 was found in the two organs until the mice died. On the other hand, no such difference was found in the isolation of virus from the brain, which contains no macrophages, and the mice eventually died from encephalitis. This difference in hepatic involvement caused by the two virus types was found to parallel a marked difference in the restriction of HSV-1 and HSV-2 replication by macrophages as measured by an infectious center assay in vitro. HSV-2 produced 17 times as many infectious centers in infected peritoneal macrophage cultures as did HSV-1. Furthermore, the HSV-2 plaques in the cell overlay were large and increasing in size, whereas the HSV-1 plaques were small and showed regression on prolonged incubation. It was shown that this diversity was unique to the macrophage population and not caused by differences in the uptake of virus by macrophages. This model involving two closely related virus types shows the importance of tissue macrophages in the primary host defense against virus infections."}
{"id": "PMID:192672", "title": "Mechanisms of resistant of herpesviruses: comparison of the effectiveness of different cell types in mediating antibody-dependent cell-mediated cytotoxicity.", "content": "Enriched populations of polymorphonuclear leukocytes (PMN) and macrophages obtained from the mammary gland and of granulocytes (PBG) and lymphocytes (PBL) prepared from peripheral blood of the same animal were compared for their ability to mediate antibody-dependent cell cytotoxocity against antibody-sensitized infectious bovine rhinotracheitis virus-infected target cells (IBR-GBK) and antibody-sensitized chicken erythrocyte targest (CRBC). The order of effectiveness was PMN leads to macrophages leads to PBG leads to PBL. The reason why PBG (86% PMN) were less than 50% as active as mammary PMN (99% PMN) was explored and discussed. The findings that PMN were more effective on a cell-to-cell basis, required less antiserum to sensitize for cytotoxicity, and destroyed IBR-GBK cells faster and more completely than other cell types could mean that PMN may be the cell type most importnat in causing early recovery from herpesvirus infections.", "contents": "Mechanisms of resistant of herpesviruses: comparison of the effectiveness of different cell types in mediating antibody-dependent cell-mediated cytotoxicity. Enriched populations of polymorphonuclear leukocytes (PMN) and macrophages obtained from the mammary gland and of granulocytes (PBG) and lymphocytes (PBL) prepared from peripheral blood of the same animal were compared for their ability to mediate antibody-dependent cell cytotoxocity against antibody-sensitized infectious bovine rhinotracheitis virus-infected target cells (IBR-GBK) and antibody-sensitized chicken erythrocyte targest (CRBC). The order of effectiveness was PMN leads to macrophages leads to PBG leads to PBL. The reason why PBG (86% PMN) were less than 50% as active as mammary PMN (99% PMN) was explored and discussed. The findings that PMN were more effective on a cell-to-cell basis, required less antiserum to sensitize for cytotoxicity, and destroyed IBR-GBK cells faster and more completely than other cell types could mean that PMN may be the cell type most importnat in causing early recovery from herpesvirus infections."}
{"id": "PMID:192673", "title": "Effect of water temperature on a herpesvirus infection of sea turtles.", "content": "The role of water temperature in the induction and maintenance of a dermal herpesvirus infection (gray-patch disease) of young, green sea turtles (Chelonia mydas) was studied under carefully controlled experimental conditions, in which the influence of other recognized stress factors was negligible. A nimals that were subjected to a gradual temperature increase from 25 to 30 degrees C, with subsequent maintenance at 30 degrees C, and those that were abruptly shifted from water at 25 degrees C to water at 30 degrees C showed a significantly shorter period before the onset of clinical signs and an increase in the severity of the lesions when compared with control animals. Animals that were subjected to a gradual increase in water temperature from 25 to 30 degrees C and a subsequent decrease to 25 degrees C, where they were maintained, had a period before onset of clinical signs and severity closer to that of control animals. Our findings indicate that both the induction of clinical gray-patch disease and the severity of the lesions are affected by water temperature and suggest that one possible means of control of this herpesvirus infection under intensive aquaculture conditions might be water temperature manipulation.", "contents": "Effect of water temperature on a herpesvirus infection of sea turtles. The role of water temperature in the induction and maintenance of a dermal herpesvirus infection (gray-patch disease) of young, green sea turtles (Chelonia mydas) was studied under carefully controlled experimental conditions, in which the influence of other recognized stress factors was negligible. A nimals that were subjected to a gradual temperature increase from 25 to 30 degrees C, with subsequent maintenance at 30 degrees C, and those that were abruptly shifted from water at 25 degrees C to water at 30 degrees C showed a significantly shorter period before the onset of clinical signs and an increase in the severity of the lesions when compared with control animals. Animals that were subjected to a gradual increase in water temperature from 25 to 30 degrees C and a subsequent decrease to 25 degrees C, where they were maintained, had a period before onset of clinical signs and severity closer to that of control animals. Our findings indicate that both the induction of clinical gray-patch disease and the severity of the lesions are affected by water temperature and suggest that one possible means of control of this herpesvirus infection under intensive aquaculture conditions might be water temperature manipulation."}
{"id": "PMID:192674", "title": "Capsular polysaccharide of Clostridium perfringens Hobbs 9.", "content": "Several closely related capsular polysaccharides were isolated from a strain of Clostridium perfringens Hobbs 9 type A by extraction of encapsulated cells with cold 0.85% NaCl. The soluble polymers were precipitated with alcohol and purified by (NH4)2SO4 fractionation, enzymatic digestion with papain and ribonuclease, and chromatography on diethylaminoethyl-Sephadex A25. The polysaccharides were composed mainly of glucose, galactose, and galactosamine. The major fraction contained these constituents (representing 77% of the dry weight) in a molar ratio of 1:1.6:1.1. All of the fractions contained phosphate and peptide material that was not removed during purification. The polysaccharides were closely related but not identical as indicated by double-diffusion-in-gel experiments. Immunoelectrophoresis in agarose demonstrated that the polysaccharides had identical mobilities and that no resolution into additional fractions occurred. The immunological activity of all the purified polysaccharides was destroyed by periodate oxidation but was unaffected by protease.", "contents": "Capsular polysaccharide of Clostridium perfringens Hobbs 9. Several closely related capsular polysaccharides were isolated from a strain of Clostridium perfringens Hobbs 9 type A by extraction of encapsulated cells with cold 0.85% NaCl. The soluble polymers were precipitated with alcohol and purified by (NH4)2SO4 fractionation, enzymatic digestion with papain and ribonuclease, and chromatography on diethylaminoethyl-Sephadex A25. The polysaccharides were composed mainly of glucose, galactose, and galactosamine. The major fraction contained these constituents (representing 77% of the dry weight) in a molar ratio of 1:1.6:1.1. All of the fractions contained phosphate and peptide material that was not removed during purification. The polysaccharides were closely related but not identical as indicated by double-diffusion-in-gel experiments. Immunoelectrophoresis in agarose demonstrated that the polysaccharides had identical mobilities and that no resolution into additional fractions occurred. The immunological activity of all the purified polysaccharides was destroyed by periodate oxidation but was unaffected by protease."}
{"id": "PMID:192675", "title": "Reliable in vivo model for latent herpes simplex virus reactivation with peripheral virus shedding.", "content": "A long-sought laboratory model, a reliable system for in vivo reactivization of latent herpes simplex infection with peripheral shedding of active virus, is present. Results demonstrate that surgical stimulation of latently infected rabbit trigeminal ganglia induces peripheral release of infectious herpes simplex virus. Virus could be cultured from the tear film in 83% of the stimulated animals' eyes within 48 h.", "contents": "Reliable in vivo model for latent herpes simplex virus reactivation with peripheral virus shedding. A long-sought laboratory model, a reliable system for in vivo reactivization of latent herpes simplex infection with peripheral shedding of active virus, is present. Results demonstrate that surgical stimulation of latently infected rabbit trigeminal ganglia induces peripheral release of infectious herpes simplex virus. Virus could be cultured from the tear film in 83% of the stimulated animals' eyes within 48 h."}
{"id": "PMID:192676", "title": "Antigenic relationships among several simian varicella-like viruses and varicella-zoster virus.", "content": "Cross-neutralization and complement fixation tests demonstrated the immunological identity of the Delta herpesvirus, the 592S virus, the Liverpool vervet monkey virus, the herpesvirus of patas monkeys, and the Medical Lake macaque virus. These viruses were isolated from diverse outbreaks of varicella-like disease in simians and from various simian species. All of the simian viruses were shown to be related to human varicella-zoster (V-Z) virus, as evidenced by the fact that immunization of monkeys with each of the simian viruses elicited the production of both neutralizing and complement-fixing antibodies to V-Z virus. However, cross-complement fixation tests indicated that the simian viruses are not so closely related to V-Z virus as they are to one another. Varicella or zoster infections in humans produced neutralizing and complement-fixing antibody responses to each of the simian viruses; the responses were more marked in zoster infections than in varicella infections but, in most patients, antibody levels produced to the simian viruses were much lower than those to the homologous V-Z virus.", "contents": "Antigenic relationships among several simian varicella-like viruses and varicella-zoster virus. Cross-neutralization and complement fixation tests demonstrated the immunological identity of the Delta herpesvirus, the 592S virus, the Liverpool vervet monkey virus, the herpesvirus of patas monkeys, and the Medical Lake macaque virus. These viruses were isolated from diverse outbreaks of varicella-like disease in simians and from various simian species. All of the simian viruses were shown to be related to human varicella-zoster (V-Z) virus, as evidenced by the fact that immunization of monkeys with each of the simian viruses elicited the production of both neutralizing and complement-fixing antibodies to V-Z virus. However, cross-complement fixation tests indicated that the simian viruses are not so closely related to V-Z virus as they are to one another. Varicella or zoster infections in humans produced neutralizing and complement-fixing antibody responses to each of the simian viruses; the responses were more marked in zoster infections than in varicella infections but, in most patients, antibody levels produced to the simian viruses were much lower than those to the homologous V-Z virus."}
{"id": "PMID:192677", "title": "Complement-fixing reactivity of Varicella-Zoster virus subunit antigens with sera from homotypic infections and heterotypic Herpes simplex virus infections.", "content": "Various subunit antigens of varicella-zoster (V-Z) virus were examined for complement-fixing (CF) activity with sera from homotypic infections and from herpes simplex virus (HSV) infections in which a CF antibody titer rise was demonstrated with crude V-Z antigen. The subunit antigens included nucleocapsids, envelopes, a soluble antigen produced from infected culture fluids by sucrose density gradient centrifugation, a soluble antigen produced by reducing the volume of clarified infected culture fluids, a soluble antigen derived from infected cell lysates, a \"viral\" antigen consisting largely of enveloped particles with a few nucleocapsids, and a cell membrane-associated antigen. None was more suitable than crude V-Z antigen for serodifferentiation of V-Z virus and HSV infections. The envelope antigen, cell membrane antigen, and the soluble antigen prepared by density gradient centrifugation showed little reactivity with sera from varicella and HSV infections, but gave high antibody titers with sera from zoster infections, suggesting that a secondary V-Z virus infection is required to produce an antibody response to these subunit antigens. Patients with varicella and zoster infections and the selected patients with HSV infections all showed significant CF antibody responses to the other V-Z subunit antigens.", "contents": "Complement-fixing reactivity of Varicella-Zoster virus subunit antigens with sera from homotypic infections and heterotypic Herpes simplex virus infections. Various subunit antigens of varicella-zoster (V-Z) virus were examined for complement-fixing (CF) activity with sera from homotypic infections and from herpes simplex virus (HSV) infections in which a CF antibody titer rise was demonstrated with crude V-Z antigen. The subunit antigens included nucleocapsids, envelopes, a soluble antigen produced from infected culture fluids by sucrose density gradient centrifugation, a soluble antigen produced by reducing the volume of clarified infected culture fluids, a soluble antigen derived from infected cell lysates, a \"viral\" antigen consisting largely of enveloped particles with a few nucleocapsids, and a cell membrane-associated antigen. None was more suitable than crude V-Z antigen for serodifferentiation of V-Z virus and HSV infections. The envelope antigen, cell membrane antigen, and the soluble antigen prepared by density gradient centrifugation showed little reactivity with sera from varicella and HSV infections, but gave high antibody titers with sera from zoster infections, suggesting that a secondary V-Z virus infection is required to produce an antibody response to these subunit antigens. Patients with varicella and zoster infections and the selected patients with HSV infections all showed significant CF antibody responses to the other V-Z subunit antigens."}
{"id": "PMID:192678", "title": "Solid-phase radioimmunoassay of human immunoglobulin M and immunoglobulin G antibodies against herpes simplex virus type 1 capsid, envelope, and excreted antigens.", "content": "A solid-phase radioimmunoassay developed in our laboratory for detection of human viral immunoglobulin M (IgM) and IgG antibodies was applied to demonstrate human class-specific antibody response against capsid, envelope, and excreted antigens of herpes simplex virus type 1. In primary infections, a clear IgM and IgG antibody response was found predominantly against the envelope components, whereas the IgM and IgG antibodies to the capsid antigen appeared more slowly. Increasing IgG antibody titers to the excreted antigen were also found in primary infections, though appearing more slowly than antibodies to the other subunit antigens. The antibody response against capsid and envelope antigens was not type specific, whereas in primary infections IgG class antibodies against the excreted antigen showed distinct type specificity. In recurrent infections, no significant level of IgM class antibodies was demonstrated, but in the patients with a severe secondary herpes simplex virus infection a definite IgM class antibody response was found against the envelope antigen. In addition, during severe secondary infections the antibody response against the excreted antigen was enhanced. The host IgG antibody response in recurrent infections was directed against the envelope and excreted antigens, whereas the level of the capsid antibodies was relatively stable.", "contents": "Solid-phase radioimmunoassay of human immunoglobulin M and immunoglobulin G antibodies against herpes simplex virus type 1 capsid, envelope, and excreted antigens. A solid-phase radioimmunoassay developed in our laboratory for detection of human viral immunoglobulin M (IgM) and IgG antibodies was applied to demonstrate human class-specific antibody response against capsid, envelope, and excreted antigens of herpes simplex virus type 1. In primary infections, a clear IgM and IgG antibody response was found predominantly against the envelope components, whereas the IgM and IgG antibodies to the capsid antigen appeared more slowly. Increasing IgG antibody titers to the excreted antigen were also found in primary infections, though appearing more slowly than antibodies to the other subunit antigens. The antibody response against capsid and envelope antigens was not type specific, whereas in primary infections IgG class antibodies against the excreted antigen showed distinct type specificity. In recurrent infections, no significant level of IgM class antibodies was demonstrated, but in the patients with a severe secondary herpes simplex virus infection a definite IgM class antibody response was found against the envelope antigen. In addition, during severe secondary infections the antibody response against the excreted antigen was enhanced. The host IgG antibody response in recurrent infections was directed against the envelope and excreted antigens, whereas the level of the capsid antibodies was relatively stable."}
{"id": "PMID:192679", "title": "Contrasting effects of immunosuppression on Theiler's virus infection in mice.", "content": "In the present study, cyclophosphamide and rabbit anti-mouse thymocyte serum were used to immunosuppress SJL/J mice infected with Theiler's mouse encephalomyelitis virus (TMEV) in order to delineate the potential mechanism(s) of virus-induced cellular injury in this infection. Whereas both immunosuppressive agents produced a significant increase in mortality, this treatment had differing effects on the pathological involvement of gray and white-matter structures in the central nervous system. The central nervous system of immunosuppressed TMEV-infected mice had increased microglial cell proliferation and neuronal necrosis, longer maintenance of high virus levels and spread of virus antigen to involve the neocortex and hippocampal complex. These observations indicate that TMEV causes a cytolotic infection of neurons and possibly other cells in gray matter. In contrast, immunosuppression produced a dramatic reduction in mononuclear inflammatory cells in the leptomeninges and spinal cord white matter of infected mice and prevented demyelination. Further, virus antigen was not detected in the leptomeninges and white matter of immunosuppressed and infected mice. These findings suggest that demyelination of TMEV infection is immune mediated.", "contents": "Contrasting effects of immunosuppression on Theiler's virus infection in mice. In the present study, cyclophosphamide and rabbit anti-mouse thymocyte serum were used to immunosuppress SJL/J mice infected with Theiler's mouse encephalomyelitis virus (TMEV) in order to delineate the potential mechanism(s) of virus-induced cellular injury in this infection. Whereas both immunosuppressive agents produced a significant increase in mortality, this treatment had differing effects on the pathological involvement of gray and white-matter structures in the central nervous system. The central nervous system of immunosuppressed TMEV-infected mice had increased microglial cell proliferation and neuronal necrosis, longer maintenance of high virus levels and spread of virus antigen to involve the neocortex and hippocampal complex. These observations indicate that TMEV causes a cytolotic infection of neurons and possibly other cells in gray matter. In contrast, immunosuppression produced a dramatic reduction in mononuclear inflammatory cells in the leptomeninges and spinal cord white matter of infected mice and prevented demyelination. Further, virus antigen was not detected in the leptomeninges and white matter of immunosuppressed and infected mice. These findings suggest that demyelination of TMEV infection is immune mediated."}
{"id": "PMID:192680", "title": "Effect of Clostridium perfrongens enterotoxin in mitochondrial respiration.", "content": "Clostridium perfringens enterotoxin caused a 26 to 41% reduction in the rate of oxygen consumption by rat liver mitochondria when various tricarboxylic acid cycle intermediates were used as substrate. However, P/O ratios were unaltered.", "contents": "Effect of Clostridium perfrongens enterotoxin in mitochondrial respiration. Clostridium perfringens enterotoxin caused a 26 to 41% reduction in the rate of oxygen consumption by rat liver mitochondria when various tricarboxylic acid cycle intermediates were used as substrate. However, P/O ratios were unaltered."}
{"id": "PMID:192681", "title": "Recent advances in pulmonary gas exchange.", "content": "Abnormal gas exchange frequently accompanies general anesthesia, and the mechanisms are probably variable and multiple. This chapter has focused on recent advances in both experimental and theoretical approaches to gas exchange in general, with emphasis on the potentially important areas for the anesthesiologist wishing to study gas during anesthesia. Experimentally it is clear that if complex multifactorial mechanisms of abnormal gas exchange are to be described, methods must developed that give significantly more information than is available by standard techniques. Even while such methods are beginning to appear, it is probable that even the most sophisticated of approaches cannot give all of the fine detail one might seek, and that critical evaluation of just what information can be obtained is of great importance. Notwithstanding the practical limitations of such methods, much can be gained by taking advantage of digital computer models of the lung. In only ten years since such models were first introduced, the understanding of complex interactions in pulmonary gas exchange has certainly exceeded the sum of previous knowledge in this area and has allowed clear-cut conclusions of fundamental importance to be reached.", "contents": "Recent advances in pulmonary gas exchange. Abnormal gas exchange frequently accompanies general anesthesia, and the mechanisms are probably variable and multiple. This chapter has focused on recent advances in both experimental and theoretical approaches to gas exchange in general, with emphasis on the potentially important areas for the anesthesiologist wishing to study gas during anesthesia. Experimentally it is clear that if complex multifactorial mechanisms of abnormal gas exchange are to be described, methods must developed that give significantly more information than is available by standard techniques. Even while such methods are beginning to appear, it is probable that even the most sophisticated of approaches cannot give all of the fine detail one might seek, and that critical evaluation of just what information can be obtained is of great importance. Notwithstanding the practical limitations of such methods, much can be gained by taking advantage of digital computer models of the lung. In only ten years since such models were first introduced, the understanding of complex interactions in pulmonary gas exchange has certainly exceeded the sum of previous knowledge in this area and has allowed clear-cut conclusions of fundamental importance to be reached."}
{"id": "PMID:192682", "title": "Detection by indirect immunofluorescence of Fc receptors in cells acutely infected with Herpes simplex virus.", "content": "In attempting to use the indirect fluorescent antibody test (IFA) to measure antibodies to herpes simplex virus (HSV), we found that all human sera gave a positive reaction with Chang liver cells infected with type 1 (HSV). All sera gave equivalent titers of 320-640 for acetone-fixed cells and about 40 for live cells (membrane fluorescence) in the presence of fluorescein-labeled antisera to human Ig; none of the sera reacted with uninfected cells. The fluorescence seen in fixed cells was primarily cytoplasmic; some cells showed a diffuse fluorescence, obscuring the demarcation between the nucleus and cytoplasm. Purified IgG from antibody-negative human sera and a purified Fc fragment of IgG were positive both for cytoplasmic and membrane fluorescence, whereas F(ab')2, IgM and IgA were unreactive. The reaction was also seen when an antiserum conjugate specific for the Fc fragment of IgG was used. The reactive IgG was present in freshly prepared plasma and serum; it could not be removed from serum either by ultracentrifugation or by serial absorption with HSV-infected cells. These findings suggest that the nonspecificity of the IFA results from the formation of low-avidity bonds between the large mass of native serum IgG and an Fc receptor on the plasma membrane and in the cytoplasm of cells infected with HSV. The results also suggest that extreme caution be exercised in attempting to use the IFA in the serodiagnosis of infections with HSV and perhaps the other human herpes-viruses.", "contents": "Detection by indirect immunofluorescence of Fc receptors in cells acutely infected with Herpes simplex virus. In attempting to use the indirect fluorescent antibody test (IFA) to measure antibodies to herpes simplex virus (HSV), we found that all human sera gave a positive reaction with Chang liver cells infected with type 1 (HSV). All sera gave equivalent titers of 320-640 for acetone-fixed cells and about 40 for live cells (membrane fluorescence) in the presence of fluorescein-labeled antisera to human Ig; none of the sera reacted with uninfected cells. The fluorescence seen in fixed cells was primarily cytoplasmic; some cells showed a diffuse fluorescence, obscuring the demarcation between the nucleus and cytoplasm. Purified IgG from antibody-negative human sera and a purified Fc fragment of IgG were positive both for cytoplasmic and membrane fluorescence, whereas F(ab')2, IgM and IgA were unreactive. The reaction was also seen when an antiserum conjugate specific for the Fc fragment of IgG was used. The reactive IgG was present in freshly prepared plasma and serum; it could not be removed from serum either by ultracentrifugation or by serial absorption with HSV-infected cells. These findings suggest that the nonspecificity of the IFA results from the formation of low-avidity bonds between the large mass of native serum IgG and an Fc receptor on the plasma membrane and in the cytoplasm of cells infected with HSV. The results also suggest that extreme caution be exercised in attempting to use the IFA in the serodiagnosis of infections with HSV and perhaps the other human herpes-viruses."}
{"id": "PMID:192685", "title": "Hypolipidemic effect of tibric acid. A comparison with clofibrate and placebo in type IV hyperlipoproteinemia.", "content": "The effects of tibric acid, clofibrate, and placebo were compared in type IV hyperlipidemic patients for a 6-month period. The patients were divided into two pathological level groups according to their baseline triglyceride levels. Compared to the placebo, both tibric acid and clofibrate reduced the mean serum triglyceride concentration in the high pathological level group; however, clofibrate was also effective in the low pathological level group. The effects on total cholesterol were less pronounced with the two drugs. No effect was observed on esterified cholesterol, phospholipids, free fatty acids, and fasting blood sugar. After a 6-week follow-up period under placebo, no rebound of the  triglyceride and cholesterol levels could be observed after discontinuation of the two active drugs. The other biochemical changes observed after each active treatment are discussed in relation to the different degree of activity of each active drug and to the different baseline levels of triglycerides.", "contents": "Hypolipidemic effect of tibric acid. A comparison with clofibrate and placebo in type IV hyperlipoproteinemia. The effects of tibric acid, clofibrate, and placebo were compared in type IV hyperlipidemic patients for a 6-month period. The patients were divided into two pathological level groups according to their baseline triglyceride levels. Compared to the placebo, both tibric acid and clofibrate reduced the mean serum triglyceride concentration in the high pathological level group; however, clofibrate was also effective in the low pathological level group. The effects on total cholesterol were less pronounced with the two drugs. No effect was observed on esterified cholesterol, phospholipids, free fatty acids, and fasting blood sugar. After a 6-week follow-up period under placebo, no rebound of the  triglyceride and cholesterol levels could be observed after discontinuation of the two active drugs. The other biochemical changes observed after each active treatment are discussed in relation to the different degree of activity of each active drug and to the different baseline levels of triglycerides."}
{"id": "PMID:192687", "title": "Free-radical formation in gamma-irradiated oriented DNA containing electron-affinic radiosensitizers.", "content": "Electron paramagnetic resonance (e.p.r.) was used to study the free radicals induced by gamma-irradiation at 77 K in oriented DNA with incorporated electronaffinic radiosensitizing compounds (4-nitroacetophenone, metronidazole, and Ro-07-0582). The observed e.p.r. spectra were compared with those obtained from pure oriented DNA, which had previously been analysed in detail and found to consist mainly of two components, arising from anion redicals on thymine, and cation radicals on guanine. The major spectral changes caused by the radiosensitizers could be explained as a considerable increase in the formation of cationic free radicals on guanine. There were also indications of the formation of anion radicals on the radiosensitizer molecules. No hydrogen-addition free radicals on thymine were observed when the radiosensitized samples were annealed, in contrast to the pure DNA samples.", "contents": "Free-radical formation in gamma-irradiated oriented DNA containing electron-affinic radiosensitizers. Electron paramagnetic resonance (e.p.r.) was used to study the free radicals induced by gamma-irradiation at 77 K in oriented DNA with incorporated electronaffinic radiosensitizing compounds (4-nitroacetophenone, metronidazole, and Ro-07-0582). The observed e.p.r. spectra were compared with those obtained from pure oriented DNA, which had previously been analysed in detail and found to consist mainly of two components, arising from anion redicals on thymine, and cation radicals on guanine. The major spectral changes caused by the radiosensitizers could be explained as a considerable increase in the formation of cationic free radicals on guanine. There were also indications of the formation of anion radicals on the radiosensitizer molecules. No hydrogen-addition free radicals on thymine were observed when the radiosensitized samples were annealed, in contrast to the pure DNA samples."}
{"id": "PMID:192688", "title": "Attenuation of Japanese encephalitis virus by brain passage of guinea pigs.", "content": "JE virus was difficult to keep alive in guinea pig brain beyond 3 days and the virus was lost after 3 days. Ten cross passages from guinea pig to mice attenuated JE virus (GP10) and the result indicated that 3 passages could induce illness in guinea pig (GP4). GP4 and GP10 did not induce viremia to mice. 0.1 ml of 1:100,000 and 1:10,000 mouse suspension of GP4 inoculated into the author subcutaneously did not cause any uncomfortable symptom.", "contents": "Attenuation of Japanese encephalitis virus by brain passage of guinea pigs. JE virus was difficult to keep alive in guinea pig brain beyond 3 days and the virus was lost after 3 days. Ten cross passages from guinea pig to mice attenuated JE virus (GP10) and the result indicated that 3 passages could induce illness in guinea pig (GP4). GP4 and GP10 did not induce viremia to mice. 0.1 ml of 1:100,000 and 1:10,000 mouse suspension of GP4 inoculated into the author subcutaneously did not cause any uncomfortable symptom."}
{"id": "PMID:192689", "title": "Ultrastructure of human prostatic epithelium. Secretion granules or virus particles?", "content": "The objective of this report is to demonstrate that only slight and superficial similarities exist between true virus particles and secretion granules in human prostatic epithelium. In spite of this, secretion granules have sometimes been called virus or virus-like particles. With the current interest in the possible role of viruses in the etiology of some human cancers, many investigations are in progress in search of human tumor viruses. The presence of RNA virus particles in normal as well as tumor tissues derived from animals and man, further complicates the picture. Also, in view of the fact that recent studies indicate an association between herpes simplex type 2 virus and cervical cancer, the possibility of the involvement of the same virus, which has a venereal mode of transmission, in prostatic and other genitourinary cancers in the human male has been considered. Investigators with peripheral interests in such studies are cautioned against making quick decisions on the nature of the \"virus-like particles\" often observed in secretory cells because these particles often happen to be cell organelles.", "contents": "Ultrastructure of human prostatic epithelium. Secretion granules or virus particles? The objective of this report is to demonstrate that only slight and superficial similarities exist between true virus particles and secretion granules in human prostatic epithelium. In spite of this, secretion granules have sometimes been called virus or virus-like particles. With the current interest in the possible role of viruses in the etiology of some human cancers, many investigations are in progress in search of human tumor viruses. The presence of RNA virus particles in normal as well as tumor tissues derived from animals and man, further complicates the picture. Also, in view of the fact that recent studies indicate an association between herpes simplex type 2 virus and cervical cancer, the possibility of the involvement of the same virus, which has a venereal mode of transmission, in prostatic and other genitourinary cancers in the human male has been considered. Investigators with peripheral interests in such studies are cautioned against making quick decisions on the nature of the \"virus-like particles\" often observed in secretory cells because these particles often happen to be cell organelles."}
{"id": "PMID:192690", "title": "Purification of Sendai virions with glutaraldehyde-treated red blood cells.", "content": "The use of glutaraldehyde (GA)-treated chicken red blood cells (RBC) for purification of Sendai virions by adsorption and elution was found to be advantageous over the use of untreated RBC. Biologic and enzymatic activities and structural components of the purified virions were compared with those of the original virions. The purified virions lost glucosamine-labeled non-proteinous materials. These materials did not relate to the expression of infectivity or cell fusion activity of Sendai virus. No evidence of disruption of Sendai virions during interaction with GA-RBC was observed. The use of GA-RBC provides a new method to prepare an unadsorbed virus fraction with a minimum contamination of hemagglutinins. The unadsorbed fraction consisted of Sendai virions with weak hemagglutinating activity and smaller amounts of the gp1(HN) polypeptide and with negligible hemolytic and cell fusion activities. The origin of these particles is discussed.", "contents": "Purification of Sendai virions with glutaraldehyde-treated red blood cells. The use of glutaraldehyde (GA)-treated chicken red blood cells (RBC) for purification of Sendai virions by adsorption and elution was found to be advantageous over the use of untreated RBC. Biologic and enzymatic activities and structural components of the purified virions were compared with those of the original virions. The purified virions lost glucosamine-labeled non-proteinous materials. These materials did not relate to the expression of infectivity or cell fusion activity of Sendai virus. No evidence of disruption of Sendai virions during interaction with GA-RBC was observed. The use of GA-RBC provides a new method to prepare an unadsorbed virus fraction with a minimum contamination of hemagglutinins. The unadsorbed fraction consisted of Sendai virions with weak hemagglutinating activity and smaller amounts of the gp1(HN) polypeptide and with negligible hemolytic and cell fusion activities. The origin of these particles is discussed."}
{"id": "PMID:192686", "title": "Psychiatric consultation services in the large general hospital: a review and a new report.", "content": "Studies are reviewed documenting increased interest in psychiatric consultation services in the general hospital, and disparities between the need for and the availability/utilization of consultation services are examined. The emergence of the eclectrically trained psychiatrist as the most acceptable consultant in the general hospital is discussed. An exploratory attiduinal questionnaire, developed and circulated to a sample of attending physicians in a midwestern university teaching hospital, yielded the following data. Thirty-nine per cent (N=96) of the 244 physicians who received the questionnaire responded. Ninety-nine per cent of the respondents agreed that readily available psychiatric consultation services should be fully operative in all large general hospitals; 88% agreed that psychiatric consultations in the general hospital must be performed by a physician with special training in  psychological medicine; 50% indicated a preference for a biologically-oriented psychiatrist, and 26% preferred a family practitioner or internist who had subsequently become a psychiatrist. The majority of respondents indicated that between July 1974 and July 1975, 1-5% of their private hospitalized patients received inhospital psychiatric consultation. Eighty-six per cent of the respondents felt the patients should be billed directly at a rate equal to other medical/surgical consultations. These data are correlated with issues involved in the utilization of psychiatric consultation in the general hospital.", "contents": "Psychiatric consultation services in the large general hospital: a review and a new report. Studies are reviewed documenting increased interest in psychiatric consultation services in the general hospital, and disparities between the need for and the availability/utilization of consultation services are examined. The emergence of the eclectrically trained psychiatrist as the most acceptable consultant in the general hospital is discussed. An exploratory attiduinal questionnaire, developed and circulated to a sample of attending physicians in a midwestern university teaching hospital, yielded the following data. Thirty-nine per cent (N=96) of the 244 physicians who received the questionnaire responded. Ninety-nine per cent of the respondents agreed that readily available psychiatric consultation services should be fully operative in all large general hospitals; 88% agreed that psychiatric consultations in the general hospital must be performed by a physician with special training in  psychological medicine; 50% indicated a preference for a biologically-oriented psychiatrist, and 26% preferred a family practitioner or internist who had subsequently become a psychiatrist. The majority of respondents indicated that between July 1974 and July 1975, 1-5% of their private hospitalized patients received inhospital psychiatric consultation. Eighty-six per cent of the respondents felt the patients should be billed directly at a rate equal to other medical/surgical consultations. These data are correlated with issues involved in the utilization of psychiatric consultation in the general hospital."}
{"id": "PMID:192691", "title": "Comparative analysis of polypeptides induced by type 1 and type 2 strains of herpes simplex virus.", "content": "The polypeptides synthesized in HEp-2 cells infected with 7 type 1 and 8 type 2 strains of herpes simplex virus were examined by PAGE. The polypeptides produced were consistent for each type and clearly different from those produced by infection with the other type.", "contents": "Comparative analysis of polypeptides induced by type 1 and type 2 strains of herpes simplex virus. The polypeptides synthesized in HEp-2 cells infected with 7 type 1 and 8 type 2 strains of herpes simplex virus were examined by PAGE. The polypeptides produced were consistent for each type and clearly different from those produced by infection with the other type."}
{"id": "PMID:192692", "title": "DNA-binding proteins in mouse cells infected with polyoma virus.", "content": "DNA-binding proteins from uninfected or polyoma virus-infected mouse cells (3T6) were isolated and compared by DNA-cellulose chromatography and SDS-PAGE. During the early phase of infection, few but significant and reproducible differences were observed. In the 0.4 M NaCl eluate, four major new polypeptides were detected in infected cells, with approximate molecular weights of 160 K, 130 K, 86 K and 81 K, the last two being compatible with previous estimates for polyoma T antigen molecular weight.", "contents": "DNA-binding proteins in mouse cells infected with polyoma virus. DNA-binding proteins from uninfected or polyoma virus-infected mouse cells (3T6) were isolated and compared by DNA-cellulose chromatography and SDS-PAGE. During the early phase of infection, few but significant and reproducible differences were observed. In the 0.4 M NaCl eluate, four major new polypeptides were detected in infected cells, with approximate molecular weights of 160 K, 130 K, 86 K and 81 K, the last two being compatible with previous estimates for polyoma T antigen molecular weight."}
{"id": "PMID:192693", "title": "Structural polypeptides of Sendai virus: analysis by tryptic peptide mapping.", "content": "Tryptic peptide patterns identified Sendai virus polypeptides polypeptides HN, HN, P,F0, NP, and M as unique gene products, and confirmed the precursor-product relationship of polypeptides F0 and F. By the same criterion, the major nucleocapsid polypeptides, P and NP, in virions were derived from the same genes as their counterparts in nucleocapsids obtained from infected cells.", "contents": "Structural polypeptides of Sendai virus: analysis by tryptic peptide mapping. Tryptic peptide patterns identified Sendai virus polypeptides polypeptides HN, HN, P,F0, NP, and M as unique gene products, and confirmed the precursor-product relationship of polypeptides F0 and F. By the same criterion, the major nucleocapsid polypeptides, P and NP, in virions were derived from the same genes as their counterparts in nucleocapsids obtained from infected cells."}
{"id": "PMID:192694", "title": "Effect of virus infection and cycloheximide treatment on the labeling of cellular phospholipids with 32 P.", "content": "The total amount and the relative proportions of labeled phospholipids were studied in chorioallantoic membrane cells (CAM), chick embryo cells (CEC) and L cells which were either infected with Newcastle disease virus (NDV), fowl plague virus (FPV) and mouse encephalomyocarditis (EMC) virus or treated with cycloheximide. In productively infected or nonproductively infected cells, the total amount of labeled phospholipids was not altered, but the relative proportions of individual phospholipids were modified. These modifications were related to the presence of viral proteins. Blocking of protein synthesis for 6 h with 7 microng cycloheximide/ml did not modify the total amount of labeled phospholipids in CAM and CEC. Less label was incorporated into cyclohexidime-treated L cells than in controls. The relative proportions of the labeled individual phospholipids were modified in all three cell types and these modifications were different from those in virus-infected cells.", "contents": "Effect of virus infection and cycloheximide treatment on the labeling of cellular phospholipids with 32 P. The total amount and the relative proportions of labeled phospholipids were studied in chorioallantoic membrane cells (CAM), chick embryo cells (CEC) and L cells which were either infected with Newcastle disease virus (NDV), fowl plague virus (FPV) and mouse encephalomyocarditis (EMC) virus or treated with cycloheximide. In productively infected or nonproductively infected cells, the total amount of labeled phospholipids was not altered, but the relative proportions of individual phospholipids were modified. These modifications were related to the presence of viral proteins. Blocking of protein synthesis for 6 h with 7 microng cycloheximide/ml did not modify the total amount of labeled phospholipids in CAM and CEC. Less label was incorporated into cyclohexidime-treated L cells than in controls. The relative proportions of the labeled individual phospholipids were modified in all three cell types and these modifications were different from those in virus-infected cells."}
{"id": "PMID:192695", "title": "The effect of phosphonoacetic acid on the in vitro replication of varicella-zoster virus.", "content": "Phosphonoacetic acid (PAA) was found to inhibit in vitro varicella-zoster virus (VZV) replication. At 100 microng/ml, PAA blocked the development and spread of VZV cytopathology in both growing and contact-inhibited cultures. Formation of virus plaques by infected cells and cell-free virus was effectively blocked at concentrations as low as 25 microng/ml. The development of nuclear and cytoplasmic virus antigens was also inhibited by PAA. Inhibition by PAA suggests that VZV DNA replication, like that of other herpes-viruses, involves a virus-specific DNA polymerase.", "contents": "The effect of phosphonoacetic acid on the in vitro replication of varicella-zoster virus. Phosphonoacetic acid (PAA) was found to inhibit in vitro varicella-zoster virus (VZV) replication. At 100 microng/ml, PAA blocked the development and spread of VZV cytopathology in both growing and contact-inhibited cultures. Formation of virus plaques by infected cells and cell-free virus was effectively blocked at concentrations as low as 25 microng/ml. The development of nuclear and cytoplasmic virus antigens was also inhibited by PAA. Inhibition by PAA suggests that VZV DNA replication, like that of other herpes-viruses, involves a virus-specific DNA polymerase."}
{"id": "PMID:192696", "title": "Isolation of Aleutian disease virus of mink in cell culture.", "content": "Aleutian disease virus, the causative agent of a persistent infection in mink, was isolated in a continuous line of feline renal cells when the cultures were maintained at reduced temperature (31.8 degrees). After serial in vitro passage of the virus at this temperature it had an optimum replication temperature of 37 degrees. An immunofluorescence focus assay was found to be suitable for virus quantitation. The cultured virus reproduced Aleutian disease in mink, and the virus could be reisolated from the mink 10--180 days after inoculation. The properties of the virus suggest that it is a member of the parvovirus group.", "contents": "Isolation of Aleutian disease virus of mink in cell culture. Aleutian disease virus, the causative agent of a persistent infection in mink, was isolated in a continuous line of feline renal cells when the cultures were maintained at reduced temperature (31.8 degrees). After serial in vitro passage of the virus at this temperature it had an optimum replication temperature of 37 degrees. An immunofluorescence focus assay was found to be suitable for virus quantitation. The cultured virus reproduced Aleutian disease in mink, and the virus could be reisolated from the mink 10--180 days after inoculation. The properties of the virus suggest that it is a member of the parvovirus group."}
{"id": "PMID:192697", "title": "Morphological transformation of rat embryonic fibroblasts by abortive herpes simplex virus infection: increased transformation rate correlated to a defective viral genotype.", "content": "Rat embryo fibroblasts were abortively infected with various stocks of herpes simplex virus type 1 strain ANG at 42 degrees. In uninfected controls all of the cells died during an 8-day incubation period at the elevated temperature, whereas varying numbers of cells in the infected cultures survived and formed colonies during subsequent incubation for 3--4 weeks at 37 degrees. All of the survivors appeared to be morphologically transformed. Two types of survivors, epithelial- and spindle-like cells, which occurred at a ratio of approximately 1:1 in all assays, could be distinguished. The observed survival rates increased from about 1 x 10-7 to 3 x 10-5, corresponding to increasing fractions (0--50%) of a defective genotype present in the infecting virus stocks. The individual survival rates do not depend exclusively on the quantity of defective virions. The existence of different subtypes of defective genomes as a further parameter is discussed.", "contents": "Morphological transformation of rat embryonic fibroblasts by abortive herpes simplex virus infection: increased transformation rate correlated to a defective viral genotype. Rat embryo fibroblasts were abortively infected with various stocks of herpes simplex virus type 1 strain ANG at 42 degrees. In uninfected controls all of the cells died during an 8-day incubation period at the elevated temperature, whereas varying numbers of cells in the infected cultures survived and formed colonies during subsequent incubation for 3--4 weeks at 37 degrees. All of the survivors appeared to be morphologically transformed. Two types of survivors, epithelial- and spindle-like cells, which occurred at a ratio of approximately 1:1 in all assays, could be distinguished. The observed survival rates increased from about 1 x 10-7 to 3 x 10-5, corresponding to increasing fractions (0--50%) of a defective genotype present in the infecting virus stocks. The individual survival rates do not depend exclusively on the quantity of defective virions. The existence of different subtypes of defective genomes as a further parameter is discussed."}
{"id": "PMID:192698", "title": "A sensitive method for the detection of herpes simplex virus type 2 specific thymidine kinase.", "content": "Thymidine kinase (TK) activity of uninfected and in vitro herpes simplex virus type 2 (HSV-2) infected human fetal lung cells was analyzed. Polyacrylamide gel electrophoresis was carried out, and subsequent incubation of equally divided gel slices in the presence of normal or anti-HSV-2 specific TK serum, together with different substrates, was performed. Small amounts of virus-specific enzyme could be detected using this combination of electrophoresis and antibodies and replacing ATP by CTP in the substrate medium.", "contents": "A sensitive method for the detection of herpes simplex virus type 2 specific thymidine kinase. Thymidine kinase (TK) activity of uninfected and in vitro herpes simplex virus type 2 (HSV-2) infected human fetal lung cells was analyzed. Polyacrylamide gel electrophoresis was carried out, and subsequent incubation of equally divided gel slices in the presence of normal or anti-HSV-2 specific TK serum, together with different substrates, was performed. Small amounts of virus-specific enzyme could be detected using this combination of electrophoresis and antibodies and replacing ATP by CTP in the substrate medium."}
{"id": "PMID:192700", "title": "Ultrastructural cytochemistry of the secretory granules of the hamster submandibular gland.", "content": "The ultrastructure and cytochemistry of the secretory granules of the male hamster submandibular salivary gland were studied; After fixation in glutaraldehyde followed by osmium tetroxide the granules exhibit a characteristic bipartite substructure, with an electron lucid crescenteric rim and a more dense central core. A differentiation into two regions of the granules could also be visualized in specimens primarily fixed in Millonig's osmium tetroxide or in potassium permanganate. The electron lucid peripheral portion of the membrane bounded secretory granules further displays a strong positive reaction after staining of ultrathin sections with the periodic acid-chromic acid-(PA-CrA)-silver technique. The strong periodate reactivity of the rim relative to the core, suggests a difference in mucin composition of the two granule regions. With the PA-CrA-silver straining technique a positive reaction was also observed within the Golgi apparatus of the acinar cells.", "contents": "Ultrastructural cytochemistry of the secretory granules of the hamster submandibular gland. The ultrastructure and cytochemistry of the secretory granules of the male hamster submandibular salivary gland were studied; After fixation in glutaraldehyde followed by osmium tetroxide the granules exhibit a characteristic bipartite substructure, with an electron lucid crescenteric rim and a more dense central core. A differentiation into two regions of the granules could also be visualized in specimens primarily fixed in Millonig's osmium tetroxide or in potassium permanganate. The electron lucid peripheral portion of the membrane bounded secretory granules further displays a strong positive reaction after staining of ultrathin sections with the periodic acid-chromic acid-(PA-CrA)-silver technique. The strong periodate reactivity of the rim relative to the core, suggests a difference in mucin composition of the two granule regions. With the PA-CrA-silver straining technique a positive reaction was also observed within the Golgi apparatus of the acinar cells."}
{"id": "PMID:192701", "title": "Cellular distribution of sarcoplasmic calcium-binding proteins by immunofluorescence.", "content": "Specific antibodies against carp paravalbumin, crayfish calcium binding protein and crayfish arginine kinase were used for indirect immunofluorescence localization of the respective proteins. Simultaneous staining of the same muscle sections with human serum containing anti-actin autoantibodies served as a probe to identify the isotropic band. Parvalbumin appears to be evenly distributed in carp white muscle. The crayfish calcium binding protein however shows a distinct localization, in the isotropic band, coincident with the actin staining. Arginine kinase, which has the same molecular weight and is extractible in the same way as the calcium binding protein does not show this distinct localization, but is evenly present in crayfish tail muscle, similarly to parvalbumin. The possible meaning of the different distribution of the two calcium binding proteins is discussed.", "contents": "Cellular distribution of sarcoplasmic calcium-binding proteins by immunofluorescence. Specific antibodies against carp paravalbumin, crayfish calcium binding protein and crayfish arginine kinase were used for indirect immunofluorescence localization of the respective proteins. Simultaneous staining of the same muscle sections with human serum containing anti-actin autoantibodies served as a probe to identify the isotropic band. Parvalbumin appears to be evenly distributed in carp white muscle. The crayfish calcium binding protein however shows a distinct localization, in the isotropic band, coincident with the actin staining. Arginine kinase, which has the same molecular weight and is extractible in the same way as the calcium binding protein does not show this distinct localization, but is evenly present in crayfish tail muscle, similarly to parvalbumin. The possible meaning of the different distribution of the two calcium binding proteins is discussed."}
{"id": "PMID:192702", "title": "[Synovial sarcoma of the neck (author's transl)].", "content": "Two cases of synovial sarcoma of the neck are reported. As it is already known from comparable literature, the extraoridinary localisation and the unusual histological pattern showing sarcomatous and synovial elements may cause major difficulties in diagnosis. In both cases the treatment consisted of radical surgical removal.", "contents": "[Synovial sarcoma of the neck (author's transl)]. Two cases of synovial sarcoma of the neck are reported. As it is already known from comparable literature, the extraoridinary localisation and the unusual histological pattern showing sarcomatous and synovial elements may cause major difficulties in diagnosis. In both cases the treatment consisted of radical surgical removal."}
{"id": "PMID:192704", "title": "Nine simultaneous primary tumors in a Boxer dog.", "content": "An aged Boxer dog had 9 distinct primary tumors: chemodectoma, osteosarcoma, bronchiolo-alveolar adenocarcinoma, interstitial cell tumor, seminoma, basal cell tumor, fibropapilloma, adrenal cortical adenoma, and pancreatic adenoma. From this report, as well as from other studies, it is clear that Boxers have special susceptibilities to a variety of tumors. Analysis of clinical data on canine tumors indicated that the risk of Boxers for multiple tumors is only slightly higher than all tumors, indicating little or no specific predisposition for multiple tumors. In Boxers, however, certain tumor types occurred more frequently as multiple primary tumors than would be expected by chance.", "contents": "Nine simultaneous primary tumors in a Boxer dog. An aged Boxer dog had 9 distinct primary tumors: chemodectoma, osteosarcoma, bronchiolo-alveolar adenocarcinoma, interstitial cell tumor, seminoma, basal cell tumor, fibropapilloma, adrenal cortical adenoma, and pancreatic adenoma. From this report, as well as from other studies, it is clear that Boxers have special susceptibilities to a variety of tumors. Analysis of clinical data on canine tumors indicated that the risk of Boxers for multiple tumors is only slightly higher than all tumors, indicating little or no specific predisposition for multiple tumors. In Boxers, however, certain tumor types occurred more frequently as multiple primary tumors than would be expected by chance."}
{"id": "PMID:192705", "title": "An estimation of the fibre type compostion of eleven skeletal muscles from New Zealand White rabbits between weaning and early maturity.", "content": "Fibre types in 11 skeletal muscles from New Zealand White rabbits were differentiated on the basis of histochemical staining reactions for Ca2+-adenosine triphosphatase (Ca2+ATPase) at pH 9-4, cytochrome oxidase, succinate dehydrogenase and L-glycerol-3-phosphate:menadione oxidoreductase activities. Using these enzyme reactions it was convenient to divide muscle fibres into three main categories in 'white' muscles and two in 'red' muscles. Between weaning and early maturity most muscles showed little change in fibre type composition, particularly when Ca2+-ATPase activity was used as the criterion. Many muscles showed an uneven distribution of fibre types in transverse sections; this was particularly so in the cases of longissimus, semitendinosus, soleus and semimembranosus proprius. The methods successful in resolving fibre types in mature muscles were not so capable of resolving fibre types in neonatal muscles.", "contents": "An estimation of the fibre type compostion of eleven skeletal muscles from New Zealand White rabbits between weaning and early maturity. Fibre types in 11 skeletal muscles from New Zealand White rabbits were differentiated on the basis of histochemical staining reactions for Ca2+-adenosine triphosphatase (Ca2+ATPase) at pH 9-4, cytochrome oxidase, succinate dehydrogenase and L-glycerol-3-phosphate:menadione oxidoreductase activities. Using these enzyme reactions it was convenient to divide muscle fibres into three main categories in 'white' muscles and two in 'red' muscles. Between weaning and early maturity most muscles showed little change in fibre type composition, particularly when Ca2+-ATPase activity was used as the criterion. Many muscles showed an uneven distribution of fibre types in transverse sections; this was particularly so in the cases of longissimus, semitendinosus, soleus and semimembranosus proprius. The methods successful in resolving fibre types in mature muscles were not so capable of resolving fibre types in neonatal muscles."}
{"id": "PMID:192707", "title": "Sensitive silica gel-packed flowcell for fluorometric detection of aflatoxins by high pressure liquid chromatography.", "content": "Aflatoxins B1, B2, G1, and G2 were quantitatively detected by high pressure liquid chromatography on a 5 micronm Lichrosorb column, using a Lichrosorb-packed flowcell in the fluorometric detector. The relationship between peak height and the amount injected was linear only up to about 2 ng but showed a linear loglog relationship. Methods for constructing and packing the flowcell are given. A guard column and venting valve were used to minimize deterioration of the analytical column and the adsorbent-packed flowcell. The method was applied to a peanut butter extract, although with the cleanup procedure used, the life expectancy of the flowcell is limited.", "contents": "Sensitive silica gel-packed flowcell for fluorometric detection of aflatoxins by high pressure liquid chromatography. Aflatoxins B1, B2, G1, and G2 were quantitatively detected by high pressure liquid chromatography on a 5 micronm Lichrosorb column, using a Lichrosorb-packed flowcell in the fluorometric detector. The relationship between peak height and the amount injected was linear only up to about 2 ng but showed a linear loglog relationship. Methods for constructing and packing the flowcell are given. A guard column and venting valve were used to minimize deterioration of the analytical column and the adsorbent-packed flowcell. The method was applied to a peanut butter extract, although with the cleanup procedure used, the life expectancy of the flowcell is limited."}
{"id": "PMID:192708", "title": "Detection and semiquantitative estimation of thyroxine and diiodothyronine in liothyronine sodium.", "content": "A method is presented for the detection and semiquantitative estimation of thyroxine and diiodothyronine in liothyronine sodium. Thyroxine is detected by thin layer chromatography, using silica gel H plates developed in butanol-acetone-ammonia (30 + 55 + 15) and sprayed with a 2,7-dichlorofluorescein solution, and estimated by comparison with standard spots. For quantitative results, a larger amount of sample is applied as a streak on a fluorescent silica gel H plate. After a 5 hr development, the band is scraped off and extracted in a small volume of 0.1N NaOH; the extract is centrifuged, transferred to a 2 cm microcell, and examined spectrophotometrically. The diiodothyronine content of liothyronine sodium is estimated by liquid chromatography on a Bondapak C18 column with 0.01N sodium perchloratebutanol-acetonitrile (1000 +62 + 188) as the eluting solvent.", "contents": "Detection and semiquantitative estimation of thyroxine and diiodothyronine in liothyronine sodium. A method is presented for the detection and semiquantitative estimation of thyroxine and diiodothyronine in liothyronine sodium. Thyroxine is detected by thin layer chromatography, using silica gel H plates developed in butanol-acetone-ammonia (30 + 55 + 15) and sprayed with a 2,7-dichlorofluorescein solution, and estimated by comparison with standard spots. For quantitative results, a larger amount of sample is applied as a streak on a fluorescent silica gel H plate. After a 5 hr development, the band is scraped off and extracted in a small volume of 0.1N NaOH; the extract is centrifuged, transferred to a 2 cm microcell, and examined spectrophotometrically. The diiodothyronine content of liothyronine sodium is estimated by liquid chromatography on a Bondapak C18 column with 0.01N sodium perchloratebutanol-acetonitrile (1000 +62 + 188) as the eluting solvent."}
{"id": "PMID:192711", "title": "Transcription of the hut operons of Salmonella typhimurium.", "content": "We have measured, by ribonucleic acid-deoxyribonucleic acid hybrid formation, the amounts of hut-specific ribonucleic acid contained in extracts of various mutant strains of Salmonella typhimurium. Our data are consistent with a model in which regulation of Hut enzyme production occurs at the level of transcription and support earlier genetic evidence indicating that all of the hut genes are transcribed in the clockwise direction on the S. typhimurium chromosome. These results also suggest that promoter sites of the two hut operons may differ in their ability to initiate transcription.", "contents": "Transcription of the hut operons of Salmonella typhimurium. We have measured, by ribonucleic acid-deoxyribonucleic acid hybrid formation, the amounts of hut-specific ribonucleic acid contained in extracts of various mutant strains of Salmonella typhimurium. Our data are consistent with a model in which regulation of Hut enzyme production occurs at the level of transcription and support earlier genetic evidence indicating that all of the hut genes are transcribed in the clockwise direction on the S. typhimurium chromosome. These results also suggest that promoter sites of the two hut operons may differ in their ability to initiate transcription."}
{"id": "PMID:192712", "title": "Resolution and purification of three periplasmic phosphatases of Salmonella typhimurium.", "content": "A survey of Salmonella typhimurium enzymes possessing phosphatase or phosphodiesterase activity was made using several different growth conditions. These studies revealed the presence of three major enzymes, all of which were subsequently purified: a cyclic 2' ,3'-nucleotide phosphodiesterase (EC 3.1.4.d), an acid hexose phosphatase (EC 3.1.3.2), and a nonspecific acid phosphatase (EC 3.1.3.2). A fourth enzyme hydrolyzed bis-(p-nitrophenyl)phosphate but none of the other substrates tested. No evidence was found for the existence of an alkaline phosphatase (EC 3.1.3.1) or a specific 5'-nucleotidase (EC 3.1.3.5) in S. typhimurium LT2. All three phosphatases could be measured efficiently in intact cells, which suggested a periplasmic location; however, they were not readily released by osmotic shock procedures. The nonspecific acid phosphatase, which was purified to apparent homogeneity, yielded a single polypeptide band on both sodium dodecyl sulfate and acidic urea gel electrophoretic systems.", "contents": "Resolution and purification of three periplasmic phosphatases of Salmonella typhimurium. A survey of Salmonella typhimurium enzymes possessing phosphatase or phosphodiesterase activity was made using several different growth conditions. These studies revealed the presence of three major enzymes, all of which were subsequently purified: a cyclic 2' ,3'-nucleotide phosphodiesterase (EC 3.1.4.d), an acid hexose phosphatase (EC 3.1.3.2), and a nonspecific acid phosphatase (EC 3.1.3.2). A fourth enzyme hydrolyzed bis-(p-nitrophenyl)phosphate but none of the other substrates tested. No evidence was found for the existence of an alkaline phosphatase (EC 3.1.3.1) or a specific 5'-nucleotidase (EC 3.1.3.5) in S. typhimurium LT2. All three phosphatases could be measured efficiently in intact cells, which suggested a periplasmic location; however, they were not readily released by osmotic shock procedures. The nonspecific acid phosphatase, which was purified to apparent homogeneity, yielded a single polypeptide band on both sodium dodecyl sulfate and acidic urea gel electrophoretic systems."}
{"id": "PMID:192713", "title": "Regulation of two phosphatases and a cyclic phosphodiesterase of Salmonella typhimurium.", "content": "The regulation of three Salmonella typhimurium phosphatases in reponse to different nutritional limitations has been studied. Two enzymes, an acid hexose phosphatase (EC 3.1.3.2) and a cyclic phosphodiesterase (EC 3.1.4.d), appear to be regulated by the cyclic adenosine 3' ,5'-monophosphate (AMP) catabolite repression system. Levels of these enzymes increased in cells grown on poor carbon sources but not in cells grown on poor nitrogen or phosphorus sources. Mutants lacking adenyl cyclase did not produce elevated levels of these enzymes in response to carbon limitation unless cyclic AMP was supplied. Mutants lacking the cyclic AMP receptor protein did not produce elevated levels of these enzymes in response to carbon limitation regardless of the presence of cyclic AMP. Since no specific induction of either enzyme could be demonstrated, these enzymes appear to be controlled solely by the cyclic AMP system. Nonspecific acid phsphatase activity (EC 3.1.3.2) increased in response to carbon, nitrogen, phosphorus, or sulfur limitation. The extent of the increase depended on growth rate, with slower growth rates favoring greater increases, and on the type of limitation. Limitation for either carbon or phosphorus resulted in maximum increases, whereas severe limitation of Mg2+ caused only a slight increase. The increase in nonspecific acid phosphatase during carbon limitation was apparently not mediated by the catabolite repression system since mutants lacking adenyl cyclase or the cyclic AMP receptor protein still produced elevated levels of this enzyme during carbon starvation. Nor did the increase during phosphorus limitation appear to be mediated by the alkaline phosphatase regulatory system. A strain of Salmonella bearing a chromosomal mutation, which caused constitutive production of alkaline phosphatase (introduced by an episome from Escherichia coli), did not have constitutive levels of nonspecific acid phosphatase.", "contents": "Regulation of two phosphatases and a cyclic phosphodiesterase of Salmonella typhimurium. The regulation of three Salmonella typhimurium phosphatases in reponse to different nutritional limitations has been studied. Two enzymes, an acid hexose phosphatase (EC 3.1.3.2) and a cyclic phosphodiesterase (EC 3.1.4.d), appear to be regulated by the cyclic adenosine 3' ,5'-monophosphate (AMP) catabolite repression system. Levels of these enzymes increased in cells grown on poor carbon sources but not in cells grown on poor nitrogen or phosphorus sources. Mutants lacking adenyl cyclase did not produce elevated levels of these enzymes in response to carbon limitation unless cyclic AMP was supplied. Mutants lacking the cyclic AMP receptor protein did not produce elevated levels of these enzymes in response to carbon limitation regardless of the presence of cyclic AMP. Since no specific induction of either enzyme could be demonstrated, these enzymes appear to be controlled solely by the cyclic AMP system. Nonspecific acid phsphatase activity (EC 3.1.3.2) increased in response to carbon, nitrogen, phosphorus, or sulfur limitation. The extent of the increase depended on growth rate, with slower growth rates favoring greater increases, and on the type of limitation. Limitation for either carbon or phosphorus resulted in maximum increases, whereas severe limitation of Mg2+ caused only a slight increase. The increase in nonspecific acid phosphatase during carbon limitation was apparently not mediated by the catabolite repression system since mutants lacking adenyl cyclase or the cyclic AMP receptor protein still produced elevated levels of this enzyme during carbon starvation. Nor did the increase during phosphorus limitation appear to be mediated by the alkaline phosphatase regulatory system. A strain of Salmonella bearing a chromosomal mutation, which caused constitutive production of alkaline phosphatase (introduced by an episome from Escherichia coli), did not have constitutive levels of nonspecific acid phosphatase."}
{"id": "PMID:192714", "title": "Inactivation of fructose diphosphatase by sucrose in yeast.", "content": "In Saccharomyces carlsbergensis, the addition of sucrose to the medium led to the inactivation of fructose diphosphatase. Sucrose itself probably triggered this process.", "contents": "Inactivation of fructose diphosphatase by sucrose in yeast. In Saccharomyces carlsbergensis, the addition of sucrose to the medium led to the inactivation of fructose diphosphatase. Sucrose itself probably triggered this process."}
{"id": "PMID:192715", "title": "Mutational analysis of serine-glycine biosynthesis in Rhodopseudomonas capsulata.", "content": "Rhodopseudomonas capsulata possesses the enzymes of both the \"phosphorylated\" and the \"non-phosphorylated\" pathways of serine biosynthesis. Certain mutants with lesions in the phosphorylated pathway are serine-glycine auxotrophs, though they still produce enzymes of the non-phosphorylated sequence. These results indicate that the phosphorylated pathway is essential for the synthesis of serine and glycine in R. capsulata under the condtions tested.", "contents": "Mutational analysis of serine-glycine biosynthesis in Rhodopseudomonas capsulata. Rhodopseudomonas capsulata possesses the enzymes of both the \"phosphorylated\" and the \"non-phosphorylated\" pathways of serine biosynthesis. Certain mutants with lesions in the phosphorylated pathway are serine-glycine auxotrophs, though they still produce enzymes of the non-phosphorylated sequence. These results indicate that the phosphorylated pathway is essential for the synthesis of serine and glycine in R. capsulata under the condtions tested."}
{"id": "PMID:192716", "title": "Specific thiamine monophosphate phosphohydrolase in Micrococcus denitrificans.", "content": "A phosphohydrolase specific for thiamine monophosphate was isolated from Micrococcus denitrificans, partially purified approximately 100-fold, and separated from acid phosphatase.", "contents": "Specific thiamine monophosphate phosphohydrolase in Micrococcus denitrificans. A phosphohydrolase specific for thiamine monophosphate was isolated from Micrococcus denitrificans, partially purified approximately 100-fold, and separated from acid phosphatase."}
{"id": "PMID:192717", "title": "Biochemical characterization of an Escherichia coli hisT strain.", "content": "An Escherichia coli hisT strain was characterized biochemically and shown to contain altered transfer ribonucleic acid and to be altered in the regulation of amino acid biosynthesis.", "contents": "Biochemical characterization of an Escherichia coli hisT strain. An Escherichia coli hisT strain was characterized biochemically and shown to contain altered transfer ribonucleic acid and to be altered in the regulation of amino acid biosynthesis."}
{"id": "PMID:192718", "title": "Differential binding of cyclic adenosine 3' ,5'-monophosphate to the cyclic adenosine 3' ,5'-monophosphate receptor protein in Escherichia coli.", "content": "Binding of cyclic adenosine 3' ,5'-monophosphate (cAMP) by the cAMP receptor protein in crude cell-free extracts of Escherichia coli was characterized. When cell were grown in glucose, binding was inhibited 50% relative to extracts from cells grown with succinate as carbon source . This inhibition could be relieved by dialysis.", "contents": "Differential binding of cyclic adenosine 3' ,5'-monophosphate to the cyclic adenosine 3' ,5'-monophosphate receptor protein in Escherichia coli. Binding of cyclic adenosine 3' ,5'-monophosphate (cAMP) by the cAMP receptor protein in crude cell-free extracts of Escherichia coli was characterized. When cell were grown in glucose, binding was inhibited 50% relative to extracts from cells grown with succinate as carbon source . This inhibition could be relieved by dialysis."}
{"id": "PMID:192719", "title": "Purification and characterization of catalytic subunit of skeletal muscle adenosine 3':5'-monophosphate-dependent protein kinase.", "content": "The catalytic subunit of rabbit skeletal muscle cyclic adenosine 3':5'-monophosphate-dependent protein kinase has been isolated in pure form. It has a molecular weight of 41,300, as determined by sedimentation equilibrium, which is in good agreement with the value of 41,000 determined by electrophoresis in the presence of sodium dodecyl sulfate. Sedimentation velocity determinations indicate that the subunit has an S20,w value of 3.12 which is essentially independent of protein concentration. These experiments are interpreted as indicating that the catalytic subunit dissociated from the holoenzyme exists as a monomer in solution. The least abundant amino acid is half-cystine, which was calculated to be present at 2.8 mol/mol of protein. The sulfhydryl reagents, N-ethylmaleimide, p-chloromercuribenzoic acid, and 5,5'-dithiobis(2-nitrobenzoic acid) inhibit the enzymatic activity of the subunit; inhibition by the two latter compounds can be reversed by 2-mercaptoethanol. Binding of 1 mol of N-ethylmaleimide/mol of protein results in almost complete inhibition. The isolated catalytic subunit contains 2.2 mol of tightly bound phosphate/mol of protein. Identification of either O-phosphoserine or O-phosphothreonine after partial acid hydrolysis indicates that at least part of the endogeneous phosphate exists as the phospho ester of one of these amino acids. Two peaks of catalytic activity corresponding to isoelectric points of pH 7.4 and 8.5 were identified by isoelectric focusing. Both forms utilize the same substrates and have similar sedimentation constants.", "contents": "Purification and characterization of catalytic subunit of skeletal muscle adenosine 3':5'-monophosphate-dependent protein kinase. The catalytic subunit of rabbit skeletal muscle cyclic adenosine 3':5'-monophosphate-dependent protein kinase has been isolated in pure form. It has a molecular weight of 41,300, as determined by sedimentation equilibrium, which is in good agreement with the value of 41,000 determined by electrophoresis in the presence of sodium dodecyl sulfate. Sedimentation velocity determinations indicate that the subunit has an S20,w value of 3.12 which is essentially independent of protein concentration. These experiments are interpreted as indicating that the catalytic subunit dissociated from the holoenzyme exists as a monomer in solution. The least abundant amino acid is half-cystine, which was calculated to be present at 2.8 mol/mol of protein. The sulfhydryl reagents, N-ethylmaleimide, p-chloromercuribenzoic acid, and 5,5'-dithiobis(2-nitrobenzoic acid) inhibit the enzymatic activity of the subunit; inhibition by the two latter compounds can be reversed by 2-mercaptoethanol. Binding of 1 mol of N-ethylmaleimide/mol of protein results in almost complete inhibition. The isolated catalytic subunit contains 2.2 mol of tightly bound phosphate/mol of protein. Identification of either O-phosphoserine or O-phosphothreonine after partial acid hydrolysis indicates that at least part of the endogeneous phosphate exists as the phospho ester of one of these amino acids. Two peaks of catalytic activity corresponding to isoelectric points of pH 7.4 and 8.5 were identified by isoelectric focusing. Both forms utilize the same substrates and have similar sedimentation constants."}
{"id": "PMID:192720", "title": "Intracellular utilization of superoxide anion by indoleamine 2,3-dioxygenase of rabbit enterocytes.", "content": "The participation of superoxide anion (O2-) in the intracellular indoleamine 2,3-dioxygenase activity was studied using the dispersed cell suspension of the rabbit small intestine. The dioxygenase activity was assayed by measuring [14C]formate released from DL-[ring-2-14C]tryptophan. The addition of diethyldiethiocarbamate, a superoxide dismutase inhibitor, markedly accelerated the intracellular dioxygenase activity while the superoxide dismutase activity decreased concomitantly. Furthermore, substrates of xanthine oxidase such as inosine, adenosine, and hypoxanthine also increased the dioxygenase activity in the cells, particularly in the presence of methylene blue. This increase was completely abolished by the addition of allopurinol, a specific inhibitor of xanthine oxidase. These results, taken together, indicate that the intracellular accumulation of O2- results in acceleration of the in situ dioxygenase activity, and that indoleamine 2,3-dioxygenase utilizes O2- in the isolated intestinal cells.", "contents": "Intracellular utilization of superoxide anion by indoleamine 2,3-dioxygenase of rabbit enterocytes. The participation of superoxide anion (O2-) in the intracellular indoleamine 2,3-dioxygenase activity was studied using the dispersed cell suspension of the rabbit small intestine. The dioxygenase activity was assayed by measuring [14C]formate released from DL-[ring-2-14C]tryptophan. The addition of diethyldiethiocarbamate, a superoxide dismutase inhibitor, markedly accelerated the intracellular dioxygenase activity while the superoxide dismutase activity decreased concomitantly. Furthermore, substrates of xanthine oxidase such as inosine, adenosine, and hypoxanthine also increased the dioxygenase activity in the cells, particularly in the presence of methylene blue. This increase was completely abolished by the addition of allopurinol, a specific inhibitor of xanthine oxidase. These results, taken together, indicate that the intracellular accumulation of O2- results in acceleration of the in situ dioxygenase activity, and that indoleamine 2,3-dioxygenase utilizes O2- in the isolated intestinal cells."}
{"id": "PMID:192721", "title": "Self-phosphorylation of cyclic guanosine 3':5'-monophosphate-dependent protein kinase from bovine lung. Effect of cyclic adenosine 3':5'-monophosphate, cyclic guanosine 3':5'-monophosphate and histone.", "content": "Incubation of purified cyclic guanosine 3':5'-monophospate-dependent protein kinase with [gamma-32P]ATP and Mg2+ led to formation of one 32P-labeled protein, Mr = 75,000, which corresponded to the single protein band detected after polyacrylamide gel electrophoresis in sodium dodecyl sulfate. When electrophoresis was performed without detergent, the labeled protein coincided with the position of cGMP-dependent protein kinase activity. Phosphorylation was enhanced severalfold by either histone or cAMP and was inhibited by the addition of cGMP. Low concentrations of cGMP blocked the stimulatory effects of cAMP or histone (or both). Since neither cAMP-dependent protein kinase nor cGMP-dependent phosphoprotein phosphatase activities were detected in the purified enzyme, we concluded that the cGMP-dependent protein kinase is a substrate for its own phosphotransferase activity and that other protein substrates (histone) and cyclic nucleotides modulate the process of self-phosphorylation.", "contents": "Self-phosphorylation of cyclic guanosine 3':5'-monophosphate-dependent protein kinase from bovine lung. Effect of cyclic adenosine 3':5'-monophosphate, cyclic guanosine 3':5'-monophosphate and histone. Incubation of purified cyclic guanosine 3':5'-monophospate-dependent protein kinase with [gamma-32P]ATP and Mg2+ led to formation of one 32P-labeled protein, Mr = 75,000, which corresponded to the single protein band detected after polyacrylamide gel electrophoresis in sodium dodecyl sulfate. When electrophoresis was performed without detergent, the labeled protein coincided with the position of cGMP-dependent protein kinase activity. Phosphorylation was enhanced severalfold by either histone or cAMP and was inhibited by the addition of cGMP. Low concentrations of cGMP blocked the stimulatory effects of cAMP or histone (or both). Since neither cAMP-dependent protein kinase nor cGMP-dependent phosphoprotein phosphatase activities were detected in the purified enzyme, we concluded that the cGMP-dependent protein kinase is a substrate for its own phosphotransferase activity and that other protein substrates (histone) and cyclic nucleotides modulate the process of self-phosphorylation."}
{"id": "PMID:192722", "title": "Mechanism of C-5 double bond introduction in the biosynthesis of cholesterol by rat liver microsomes.", "content": "The dehydrogenation reaction of cholest-7-en-3beta-ol (I) to cholesta-5,7-dien-3beta-ol (II) in the presence of NADH was studied in rat liver microsomes and in microsomal acetone powder preparations, using [3alpha-3H]cholest-7-en-3beta-ol. It was found that the reaction was inhibited by menadione, adenosine diphosphate, potassium ferricyanide, and cytochrome c while p-cresol had no effect. These results indicated the participation of a microsomal electron transport system in the dehydrogenation of cholest-7-en-3beta-ol. The conversion of cholest-7-en-3beta-ol to cholesta-5,7-dien-3beta-ol was also observed in the absence of NADH when ascorbic acid was included in the incubation mixture. However, the ascorbic acid-catalyzed dehydrogenation was not inhibited by potassium ferricyanide. Immunological evidence that microsomal cytochrome b5 is involved in the dehydrogenation of (I) to (II) was obtained. Antibodies specific for rat liver microsomal cytochrome b5 were elicited in rabbits. The anticytochrome b5 immunoglobulin fraction inhibited rat liver microsomal NADH-cytochrome c reductase but not NADPH-cytochrome c reductase. Also, the extent of reduction of cytochrome b5 was not affected by the antibodies. The conversion of (I) to (II) by rat liver microsomes was inhibited (73%) by anticytochrome b5 immunoglobulin at a ratio of microsomal protein:immunoglobulin of 1:5.6. These results are consistent with the participation of microsomal cytochrome b5 in the introduction of the C-5 double bond in cholesterol biosynthesis. A close analogy of the microsomal dehydrogenation of fatty acids and of cholest-7-en-3beta-ol is apparent and this suggests a possible similarity in the mechanisms of the two reactions.", "contents": "Mechanism of C-5 double bond introduction in the biosynthesis of cholesterol by rat liver microsomes. The dehydrogenation reaction of cholest-7-en-3beta-ol (I) to cholesta-5,7-dien-3beta-ol (II) in the presence of NADH was studied in rat liver microsomes and in microsomal acetone powder preparations, using [3alpha-3H]cholest-7-en-3beta-ol. It was found that the reaction was inhibited by menadione, adenosine diphosphate, potassium ferricyanide, and cytochrome c while p-cresol had no effect. These results indicated the participation of a microsomal electron transport system in the dehydrogenation of cholest-7-en-3beta-ol. The conversion of cholest-7-en-3beta-ol to cholesta-5,7-dien-3beta-ol was also observed in the absence of NADH when ascorbic acid was included in the incubation mixture. However, the ascorbic acid-catalyzed dehydrogenation was not inhibited by potassium ferricyanide. Immunological evidence that microsomal cytochrome b5 is involved in the dehydrogenation of (I) to (II) was obtained. Antibodies specific for rat liver microsomal cytochrome b5 were elicited in rabbits. The anticytochrome b5 immunoglobulin fraction inhibited rat liver microsomal NADH-cytochrome c reductase but not NADPH-cytochrome c reductase. Also, the extent of reduction of cytochrome b5 was not affected by the antibodies. The conversion of (I) to (II) by rat liver microsomes was inhibited (73%) by anticytochrome b5 immunoglobulin at a ratio of microsomal protein:immunoglobulin of 1:5.6. These results are consistent with the participation of microsomal cytochrome b5 in the introduction of the C-5 double bond in cholesterol biosynthesis. A close analogy of the microsomal dehydrogenation of fatty acids and of cholest-7-en-3beta-ol is apparent and this suggests a possible similarity in the mechanisms of the two reactions."}
{"id": "PMID:192723", "title": "Purification of phosphoprotein phosphatase from bovine cardiac muscle that catalyzes dephosphorylation of cyclic AMP-binding protein component of protein kinase.", "content": "A phosphoprotein phosphatase that catalyzes the dephosphorylation of cyclic adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase from bovine cardiac muscle has been purified to homogeneity by a modification of the procedure of Brandt et al. (Brandt, H., Capulong, Z.L., and Lee, E. Y. C. (1975) J. Biol. Chem. 250, 8038-8044). Treatment of the enzyme preparation with ethanol during the early stages of purification results in activation concomitant with reduction in molecular weight to 30,000. The purified activated enzyme has a Km for phospho-protein kinase in the presence or absence of 1.2 mM Mn2+ of 5 and 22 micronM, respectively. Phosphatase activity on phospho-protein kinase but not on other phosphoprotein substrates was cAMP-dependent. This selective activation by cAMP reflects the preference of the phosphatase for the free, phosphorylated cAMP-binding protein rather than the phosphoholoenzyme.", "contents": "Purification of phosphoprotein phosphatase from bovine cardiac muscle that catalyzes dephosphorylation of cyclic AMP-binding protein component of protein kinase. A phosphoprotein phosphatase that catalyzes the dephosphorylation of cyclic adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase from bovine cardiac muscle has been purified to homogeneity by a modification of the procedure of Brandt et al. (Brandt, H., Capulong, Z.L., and Lee, E. Y. C. (1975) J. Biol. Chem. 250, 8038-8044). Treatment of the enzyme preparation with ethanol during the early stages of purification results in activation concomitant with reduction in molecular weight to 30,000. The purified activated enzyme has a Km for phospho-protein kinase in the presence or absence of 1.2 mM Mn2+ of 5 and 22 micronM, respectively. Phosphatase activity on phospho-protein kinase but not on other phosphoprotein substrates was cAMP-dependent. This selective activation by cAMP reflects the preference of the phosphatase for the free, phosphorylated cAMP-binding protein rather than the phosphoholoenzyme."}
{"id": "PMID:192724", "title": "Glucuronosyl-N-acetylglucosaminyl pyrophosphoryldolichol. Formation in SV40-transformed human lung fibroblasts and biosynthesis in rat lung microsomal preparations.", "content": "Incubation of SV40-transformed human lung fibroblasts with [3H]glucosamine for 1 h. followed by chloroform:methanol extraction and thin layer chromatographic analysis, revealed the presence of a major radioactive lipid that was isolated and characterized as GIcUA-(1 leads to 4)-GlcNAc-P-P-dolichol. An identical lipid was formed in smaller quantities under similar incubation conditions in several fibroblastic lines, HeLa cells, and in mouse L cells. Rat lung microsomal preparations catalyze the synthesis of the disaccharide lipid in the following sequence of reactions: UDP-[3H]GlcNAc + dolichol-P leads to [3H]GlcNAc-P-P-dolichol (1) [3H]GlcNAc-P-P-dolichol + UDP-[14C]GlcUA leads to [14C]GlcUA-[3H]GlcNAc-P-P-dolichol (2) The double-labeled lipid was identical to the lipid isolated from SV40-transformed fibroblasts with regard to its behavior on thin layer and silicic acid chromatography. Further, the double-labeled disaccharide released from the lipid by mild acid hydrolysis was identical to GlcUA-(1 leads to 4)-GlcNAc in its chromatographic and electrophoretic behavior and in its composition. The occurrence of a polyprenol derivative of GlcUA-(1 leads to 4)-GlcNAc suggests a possible role for this lipid in the biosynthesis of the repeating disaccharide units of proteoglycans, such as heparin.", "contents": "Glucuronosyl-N-acetylglucosaminyl pyrophosphoryldolichol. Formation in SV40-transformed human lung fibroblasts and biosynthesis in rat lung microsomal preparations. Incubation of SV40-transformed human lung fibroblasts with [3H]glucosamine for 1 h. followed by chloroform:methanol extraction and thin layer chromatographic analysis, revealed the presence of a major radioactive lipid that was isolated and characterized as GIcUA-(1 leads to 4)-GlcNAc-P-P-dolichol. An identical lipid was formed in smaller quantities under similar incubation conditions in several fibroblastic lines, HeLa cells, and in mouse L cells. Rat lung microsomal preparations catalyze the synthesis of the disaccharide lipid in the following sequence of reactions: UDP-[3H]GlcNAc + dolichol-P leads to [3H]GlcNAc-P-P-dolichol (1) [3H]GlcNAc-P-P-dolichol + UDP-[14C]GlcUA leads to [14C]GlcUA-[3H]GlcNAc-P-P-dolichol (2) The double-labeled lipid was identical to the lipid isolated from SV40-transformed fibroblasts with regard to its behavior on thin layer and silicic acid chromatography. Further, the double-labeled disaccharide released from the lipid by mild acid hydrolysis was identical to GlcUA-(1 leads to 4)-GlcNAc in its chromatographic and electrophoretic behavior and in its composition. The occurrence of a polyprenol derivative of GlcUA-(1 leads to 4)-GlcNAc suggests a possible role for this lipid in the biosynthesis of the repeating disaccharide units of proteoglycans, such as heparin."}
{"id": "PMID:192725", "title": "Ionic inhibition of catalytic phosphorylation of histone by bovine brain protein kinase.", "content": "The effects of various ions commonly found in protein kinase assays upon the rate of histone phosphorylation catalyzed by the highly purified bovine brain enzyme, protein kinase I, have been investigated. Sodium, potassium, and magnesium were found to inhibit histone phosphorylation by protein kinase I  in a similar manner. The degree of inhibition by any of these cations was demonstrated to be directly proportional to the square root of the ionic strength of the assay medium. The relationship between the ionic strength of the assay medium and the rate of histone phosphorylation catalyzed by protein kinase I was employed to correct the rate of histone phosphorylation at various magnesium acetate concentrations to a standard ionic strength. When this was done an analysis of the previously postulated rate law for histone phosphorylation c atalyzed by protein kinase I gave a binding constant for the magnesium-ATP complex which was in agreement with that expected for this complex on  the basis of various binding constants available in the literature. These results demonstrate that it is unnecessary to postulate a specific ion inhibition process for protein kinase I by the ions employed in this study. They also support the reasonable assumption that magnesium ion binds to ATP at or prior to the rate-determining step in histone phosphorylation catalyzed by protein kinase I. The expression developed in this paper for the effect of ionic strength upon protein kinase I activity can now be used to correct activity measurements made under various assay conditions to a standard assay state, allowing facile comparisons of kinetic data. It should be possible to develop similar expressions for other protein kinases and substrates to permit useful interpretation of kinetic data.", "contents": "Ionic inhibition of catalytic phosphorylation of histone by bovine brain protein kinase. The effects of various ions commonly found in protein kinase assays upon the rate of histone phosphorylation catalyzed by the highly purified bovine brain enzyme, protein kinase I, have been investigated. Sodium, potassium, and magnesium were found to inhibit histone phosphorylation by protein kinase I  in a similar manner. The degree of inhibition by any of these cations was demonstrated to be directly proportional to the square root of the ionic strength of the assay medium. The relationship between the ionic strength of the assay medium and the rate of histone phosphorylation catalyzed by protein kinase I was employed to correct the rate of histone phosphorylation at various magnesium acetate concentrations to a standard ionic strength. When this was done an analysis of the previously postulated rate law for histone phosphorylation c atalyzed by protein kinase I gave a binding constant for the magnesium-ATP complex which was in agreement with that expected for this complex on  the basis of various binding constants available in the literature. These results demonstrate that it is unnecessary to postulate a specific ion inhibition process for protein kinase I by the ions employed in this study. They also support the reasonable assumption that magnesium ion binds to ATP at or prior to the rate-determining step in histone phosphorylation catalyzed by protein kinase I. The expression developed in this paper for the effect of ionic strength upon protein kinase I activity can now be used to correct activity measurements made under various assay conditions to a standard assay state, allowing facile comparisons of kinetic data. It should be possible to develop similar expressions for other protein kinases and substrates to permit useful interpretation of kinetic data."}
{"id": "PMID:192726", "title": "Ca2+-dependent effect of ATP on spin-labeled sarcoplasmic reticulum.", "content": "Vesicular fragments of sarcoplasmic reticulum (SR) were labeled with the --SH-directed spin label 2,2,6,6-tetra-methyl,4-amino(N-iodoacetamide). Colorimetric titrations of the remaining --SH residues and determinations of unbound spin label indicated that primarily 3 residues/enzyme molecule were labeled under saturating conditions. This labeling was accompanied by minimal losses in activity, providing precautions were taken to prevent sulfhydryl oxidation during the labeling process.  Additions of ATP produced a new \"highly constrained\" component in the ESR spectrum of the labeled SR, an effect not noted in previous studies. It is demonstrated that the changes produced by ATP are reversible, and require both substrate binding and Ca2+ binding. However, hydrolysis of the substrate is not required. It is further demonstrated that the labeled residue(s) responsible for the spectral change is not in the immediate vicinity of the ATP binding site. It is apparent that the observed spectral change is related to a conformational effect of ATP and Ca2+ on the ATPase protein, which is associated with a large free energy change occurring on binding. It is also suggested that the conformational effect extends to a significant distance from the nucleotide binding site and may be a precursory step to Ca2+ translocation.", "contents": "Ca2+-dependent effect of ATP on spin-labeled sarcoplasmic reticulum. Vesicular fragments of sarcoplasmic reticulum (SR) were labeled with the --SH-directed spin label 2,2,6,6-tetra-methyl,4-amino(N-iodoacetamide). Colorimetric titrations of the remaining --SH residues and determinations of unbound spin label indicated that primarily 3 residues/enzyme molecule were labeled under saturating conditions. This labeling was accompanied by minimal losses in activity, providing precautions were taken to prevent sulfhydryl oxidation during the labeling process.  Additions of ATP produced a new \"highly constrained\" component in the ESR spectrum of the labeled SR, an effect not noted in previous studies. It is demonstrated that the changes produced by ATP are reversible, and require both substrate binding and Ca2+ binding. However, hydrolysis of the substrate is not required. It is further demonstrated that the labeled residue(s) responsible for the spectral change is not in the immediate vicinity of the ATP binding site. It is apparent that the observed spectral change is related to a conformational effect of ATP and Ca2+ on the ATPase protein, which is associated with a large free energy change occurring on binding. It is also suggested that the conformational effect extends to a significant distance from the nucleotide binding site and may be a precursory step to Ca2+ translocation."}
{"id": "PMID:192727", "title": "Phospholipid synthesis in isolated fat cells. Studies of microsomal diacylglycerol cholinephosphotransferase and diacylglycerol ethanolaminephosphotransferase activities.", "content": "Diacylglycerol cholinephosphotransferase (EC 2.7.8.2) and diacylglycerol ethanolaminephosphotransferase (EC 2.7.8.1) activities were investigated in microsomes from isolated rat fat cells. Assays based on the conversion of CDP-[14C]choline of CDP-[14C]ethanolamine to phosphatidylcholine or phosphatidylethanolamine utilized ethanol-dispersed diacylglycerols and 1 to 5 microng of protein. Cholinephosphotransferase and ethanolaminephosphotransferase activities had similar dependences on MgCl2 and pH, and were inhibited similarly by CaCl2, organic solvents, Triton X-100, Tween 20, and dithiothreitol. Ethylene glycol bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid stimulated both activities similarly. With 1,2-dioleoyl-sn-glycerol, the cholinephosphotransferase activity had an apparent Km for CDP-choline of 23.9 micronM and a V max of 8.54 nmol/min/mg. CDP-ethanolamine and CDP were competitive inhibitors of the cholinephosphotransferase activity (apparent Kl values of 227 micronM and 360 micronM, respectively). With 1,2-dioleoyl-sn-glycerol, the ethanolaminephosphotransferase activity had an apparent Km of 18.3 micronM for CDP-ethanolamine and a V max of 1.14 nmol/min/mg. CDP-choline appeared to be a noncompetitive inhibitor of the ethanolaminephosphotransferase activity (apparent Kl of 1620 micronM). Inhibition of the ethanolaminephosphotransferase activity by CDP appeared to be of a mixed type. The dependences on diacylglycerols containing fatty acids 6 to 18 carbons in length were investigated...", "contents": "Phospholipid synthesis in isolated fat cells. Studies of microsomal diacylglycerol cholinephosphotransferase and diacylglycerol ethanolaminephosphotransferase activities. Diacylglycerol cholinephosphotransferase (EC 2.7.8.2) and diacylglycerol ethanolaminephosphotransferase (EC 2.7.8.1) activities were investigated in microsomes from isolated rat fat cells. Assays based on the conversion of CDP-[14C]choline of CDP-[14C]ethanolamine to phosphatidylcholine or phosphatidylethanolamine utilized ethanol-dispersed diacylglycerols and 1 to 5 microng of protein. Cholinephosphotransferase and ethanolaminephosphotransferase activities had similar dependences on MgCl2 and pH, and were inhibited similarly by CaCl2, organic solvents, Triton X-100, Tween 20, and dithiothreitol. Ethylene glycol bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid stimulated both activities similarly. With 1,2-dioleoyl-sn-glycerol, the cholinephosphotransferase activity had an apparent Km for CDP-choline of 23.9 micronM and a V max of 8.54 nmol/min/mg. CDP-ethanolamine and CDP were competitive inhibitors of the cholinephosphotransferase activity (apparent Kl values of 227 micronM and 360 micronM, respectively). With 1,2-dioleoyl-sn-glycerol, the ethanolaminephosphotransferase activity had an apparent Km of 18.3 micronM for CDP-ethanolamine and a V max of 1.14 nmol/min/mg. CDP-choline appeared to be a noncompetitive inhibitor of the ethanolaminephosphotransferase activity (apparent Kl of 1620 micronM). Inhibition of the ethanolaminephosphotransferase activity by CDP appeared to be of a mixed type. The dependences on diacylglycerols containing fatty acids 6 to 18 carbons in length were investigated..."}
{"id": "PMID:192728", "title": "Preliminary results using superfractionation in the treatment of glioblastoma multiforme.", "content": "Preliminary results of a phase I--phase II trial of the use of superfractionation radiation treatment in the treatment of Glioblastoma Multiforme are presented with the rationale for this form of treatment. A comparison is made with an historic control group from the same institution, and a significant improvement in survival is noted in the experimental group over this control group.", "contents": "Preliminary results using superfractionation in the treatment of glioblastoma multiforme. Preliminary results of a phase I--phase II trial of the use of superfractionation radiation treatment in the treatment of Glioblastoma Multiforme are presented with the rationale for this form of treatment. A comparison is made with an historic control group from the same institution, and a significant improvement in survival is noted in the experimental group over this control group."}
{"id": "PMID:192729", "title": "Putrescine transport is greatly increased in human fibroblasts initiated to proliferate.", "content": "Putrescine (diaminobutane) was previously found to stimulate proliferation of human fibroblasts in tissue culture, and a growth factor produced by these cells was identified as putrescine. In the present paper putrescine transport is studied. The rate of putrescine transport was dependent on temperature, and most of the labeled putrescine was retained by the cells after washing with excess unlabeled putrescine. The concentration of radioactivity after a [14 C]putrescine pulse was 85 times higher in the cells than in the medium, and over 95% of the radioactivity in the cells was as unchanged putrescine. Butanol treatment removed 70% of the radioactivity from the cells. The calculated Km was about the same for rapidly growing and for starved cultures, while Vmax was higher for the former than for the latter cultures. Putrescine transport was inhibited to varying degrees by other polyamines, but not by amino acids or divalent cations. Stimulation of cell proliferation by serum was followed by an 18-100-fold increase in the rate of putrescine transport, which was not inhibitable with cyclic AMP, dibutyryl cyclic AMP, or prostaglandin E1. Removal of serum resulted in a rapid decrease in the rate of putrescine transport. Insulin in low serum medium and trypsin in the absence of serum also accelerated putrescine transport. Moreover, the rate of putrescine transport was dependent on cell density. It was faster in sparsely populated than in densely populated cultures. SV40-transformed human fibroblasts responded to addition and removal of serum in the same way as the untransformed parent cell line.", "contents": "Putrescine transport is greatly increased in human fibroblasts initiated to proliferate. Putrescine (diaminobutane) was previously found to stimulate proliferation of human fibroblasts in tissue culture, and a growth factor produced by these cells was identified as putrescine. In the present paper putrescine transport is studied. The rate of putrescine transport was dependent on temperature, and most of the labeled putrescine was retained by the cells after washing with excess unlabeled putrescine. The concentration of radioactivity after a [14 C]putrescine pulse was 85 times higher in the cells than in the medium, and over 95% of the radioactivity in the cells was as unchanged putrescine. Butanol treatment removed 70% of the radioactivity from the cells. The calculated Km was about the same for rapidly growing and for starved cultures, while Vmax was higher for the former than for the latter cultures. Putrescine transport was inhibited to varying degrees by other polyamines, but not by amino acids or divalent cations. Stimulation of cell proliferation by serum was followed by an 18-100-fold increase in the rate of putrescine transport, which was not inhibitable with cyclic AMP, dibutyryl cyclic AMP, or prostaglandin E1. Removal of serum resulted in a rapid decrease in the rate of putrescine transport. Insulin in low serum medium and trypsin in the absence of serum also accelerated putrescine transport. Moreover, the rate of putrescine transport was dependent on cell density. It was faster in sparsely populated than in densely populated cultures. SV40-transformed human fibroblasts responded to addition and removal of serum in the same way as the untransformed parent cell line."}
{"id": "PMID:192730", "title": "Characterization of surface glycoproteins of mouse lymphoid cells.", "content": "We have labeled exposed surface glycoproteins of mouse lymphoid cells by the galactose oxidase-tritated sodium borohydride technique. The labeled glyco-proteins were separated by polyacrylamide slab gel electrophoresis and visualized by autoradiography (fluorography). The major thymocyte surface proteins have molecular weights of 170,000 and 125,000. Thymocytes from TL antigen-positive mouse strains showed an additional band with a molecular weight of 27,000. Highly purified T lymphocytes contain two major surface glycoproteins with molecular weights of 180,000 and 125,000. Purified B lymphocytes have one major surface glycoprotein with a molecular weight of 210,000. When T lymphocytes are stimulated in vitro by concanavalin A or phytohemag-glutinin, the major proteins characteristic of T cells are relatively weakly labeled, but new components of lower molecular weights appear on the cell surface. A similar change is seen in B lymphocytes stimulated by Escherichia coli lipopolysaccharide. T lymphoblasts isolated from mixed lymphocyte cultures show a slightly different surface glycoprotein pattern. A polypeptide with a molecular weight of 57,000, which was labeled without enzymatic treatment by tritiated sodium borohydride alone, is strongly labeled in proliferating cells.", "contents": "Characterization of surface glycoproteins of mouse lymphoid cells. We have labeled exposed surface glycoproteins of mouse lymphoid cells by the galactose oxidase-tritated sodium borohydride technique. The labeled glyco-proteins were separated by polyacrylamide slab gel electrophoresis and visualized by autoradiography (fluorography). The major thymocyte surface proteins have molecular weights of 170,000 and 125,000. Thymocytes from TL antigen-positive mouse strains showed an additional band with a molecular weight of 27,000. Highly purified T lymphocytes contain two major surface glycoproteins with molecular weights of 180,000 and 125,000. Purified B lymphocytes have one major surface glycoprotein with a molecular weight of 210,000. When T lymphocytes are stimulated in vitro by concanavalin A or phytohemag-glutinin, the major proteins characteristic of T cells are relatively weakly labeled, but new components of lower molecular weights appear on the cell surface. A similar change is seen in B lymphocytes stimulated by Escherichia coli lipopolysaccharide. T lymphoblasts isolated from mixed lymphocyte cultures show a slightly different surface glycoprotein pattern. A polypeptide with a molecular weight of 57,000, which was labeled without enzymatic treatment by tritiated sodium borohydride alone, is strongly labeled in proliferating cells."}
{"id": "PMID:192731", "title": "Identification and transmembranous localization of active cytochrome oxidase in reconstituted membranes of purified phospholipids by electron microscopy.", "content": "Cytochrome oxidase vesicles with high oxidase activity and respiratory control ratio (greater than 3.5) were characterized by the freeze-etch technique for electron microscopy. By the use of this technique, cytochrome oxidase is shown to be an inner membrane particle. By locating cross-fractured vesicles in the same preparation, cytochrome oxidase particles are shown to extend across the phospholipid bilayer membranes. When cytochrome oxidase is added to preformed liposomes respiratory control is not observed, but high oxidase activity is maintained. In this preparation the cytochrome oxidase particles are located on the outer vesicle membrane surface. These observations provide direct evidence that cytochrome oxidase is found in a transmembranous position in closed, activecytochrome oxidase vesicles having respiratory control.", "contents": "Identification and transmembranous localization of active cytochrome oxidase in reconstituted membranes of purified phospholipids by electron microscopy. Cytochrome oxidase vesicles with high oxidase activity and respiratory control ratio (greater than 3.5) were characterized by the freeze-etch technique for electron microscopy. By the use of this technique, cytochrome oxidase is shown to be an inner membrane particle. By locating cross-fractured vesicles in the same preparation, cytochrome oxidase particles are shown to extend across the phospholipid bilayer membranes. When cytochrome oxidase is added to preformed liposomes respiratory control is not observed, but high oxidase activity is maintained. In this preparation the cytochrome oxidase particles are located on the outer vesicle membrane surface. These observations provide direct evidence that cytochrome oxidase is found in a transmembranous position in closed, activecytochrome oxidase vesicles having respiratory control."}
{"id": "PMID:192732", "title": "Nuclear mutations affecting mitochondrial structure and function in Chlamydomonas.", "content": "Wild type cells of the green alga Chlamydomonas reinhardtii can grow in the in the dark by taking up and respiring exogenously supplied acetate. Obligate photoautotrophic (dark dier, dk) mutants of this alga have been selected which grow at near wild type rates in the light, but rapidly die when transferred to darkness because of defects in mitochondrial structure and function. In crosses of the dk mutants to wild type, the majority of the mutants are inherited in a mendelian fashion, although two have been isolated which are inherited in a clearly nonmendelian fashion. Nine mendelian dk mutants have been analyzed in detail, and belong to eight different complementation groups representing eight gene loci. These mutants have been tentatively grouped into three classes on the basis of the pleiotropic nature of their phenotypic defects. Mutants in Class I have gross alterations in the ultrastructure of their mitochondrial inner membranes together with deficiencies in cytochrome oxidase and antimycin/rotenone-sensitive NADH-cytochrome c reductase activities. Mutants in Class II have a variety of less severe alterations in mitochondrial ultrastructure and deficiencies in cytochrome oxidase activity. Mutants in Class III have normal or near normal mitochondrial ultrastructure and reduced cytochrome oxidase activity. Eight of the nine mutants show corresponding reductions in cyanide-sensitive respiration.", "contents": "Nuclear mutations affecting mitochondrial structure and function in Chlamydomonas. Wild type cells of the green alga Chlamydomonas reinhardtii can grow in the in the dark by taking up and respiring exogenously supplied acetate. Obligate photoautotrophic (dark dier, dk) mutants of this alga have been selected which grow at near wild type rates in the light, but rapidly die when transferred to darkness because of defects in mitochondrial structure and function. In crosses of the dk mutants to wild type, the majority of the mutants are inherited in a mendelian fashion, although two have been isolated which are inherited in a clearly nonmendelian fashion. Nine mendelian dk mutants have been analyzed in detail, and belong to eight different complementation groups representing eight gene loci. These mutants have been tentatively grouped into three classes on the basis of the pleiotropic nature of their phenotypic defects. Mutants in Class I have gross alterations in the ultrastructure of their mitochondrial inner membranes together with deficiencies in cytochrome oxidase and antimycin/rotenone-sensitive NADH-cytochrome c reductase activities. Mutants in Class II have a variety of less severe alterations in mitochondrial ultrastructure and deficiencies in cytochrome oxidase activity. Mutants in Class III have normal or near normal mitochondrial ultrastructure and reduced cytochrome oxidase activity. Eight of the nine mutants show corresponding reductions in cyanide-sensitive respiration."}
{"id": "PMID:192733", "title": "Lipogenesis and the synthesis and secretion of very low density lipoprotein by avian liver cells in nonproliferating monolayer culture. Hormonal effects.", "content": "The nonproliferating chicken liver cell culture system described yields cell monolayers with morphological and lipogenic properties characteristic of the physiological-nutritional state of donor animals. Synthesis and secretion of fatty acid, cholesterol, and very low density lipoprotein (VLDL) occur at in vivo rates and respond to hormones and agents which affect these processes in vivo. Cells derived from fed chickens maintain high rates of synthesis of fatty acid and cholesterol for several days if insulin is present in the medium. High rates of fatty acid synthesis are correlated with the appearance of membrane-enclosed triglyceride-rich vesicles in the cytoplasm; deletion of insulin causes a decrease (T1/2 = 22 h) in fatty acid synthetic activity. Addition of glucagon or cyclic AMP (cAMP) causes an immediate cessation of fatty acid synthesis and blocks the appearance of the triglyceride-rich vesicles. Fatty acid synthesis in liver cells prepared from fasted chickens is less than 5% that of cells from fed animals. After 2-3 days in culture with serum-free medium containing insulin +/- triiodothyronine, fatty acid synthesis is restored to normal; glucagon or dibutyryl cAMP blocks this recovery. Liver cells derived from estradiol-treated chickens synthesize and secrete VLDL for at least 48 h in culture. Electron micrographs of these cells reveal more extensive development of the rough endoplasmic reticulum and Golgi complex compared to cells from untreated chickens. Whereas [3H]leucine incorporation into total protein is unaffected by estrogen treatment, [3H]leucine incorporation into cellular and secreted immunoprecipitable VLDL is markedly increased indicating specific activation of VLDL apopeptide synthesis; 8-10% of the labeled protein synthesized and secreted is VLDL. Dodecyl sulfate-acrylamide gel electrophoresis of immunoprecipitated 3H-VLDL reveals three major apopepetides of 300,000, 11,000, and 8,000 daltons corresponding to those of purified chicken VLDL.", "contents": "Lipogenesis and the synthesis and secretion of very low density lipoprotein by avian liver cells in nonproliferating monolayer culture. Hormonal effects. The nonproliferating chicken liver cell culture system described yields cell monolayers with morphological and lipogenic properties characteristic of the physiological-nutritional state of donor animals. Synthesis and secretion of fatty acid, cholesterol, and very low density lipoprotein (VLDL) occur at in vivo rates and respond to hormones and agents which affect these processes in vivo. Cells derived from fed chickens maintain high rates of synthesis of fatty acid and cholesterol for several days if insulin is present in the medium. High rates of fatty acid synthesis are correlated with the appearance of membrane-enclosed triglyceride-rich vesicles in the cytoplasm; deletion of insulin causes a decrease (T1/2 = 22 h) in fatty acid synthetic activity. Addition of glucagon or cyclic AMP (cAMP) causes an immediate cessation of fatty acid synthesis and blocks the appearance of the triglyceride-rich vesicles. Fatty acid synthesis in liver cells prepared from fasted chickens is less than 5% that of cells from fed animals. After 2-3 days in culture with serum-free medium containing insulin +/- triiodothyronine, fatty acid synthesis is restored to normal; glucagon or dibutyryl cAMP blocks this recovery. Liver cells derived from estradiol-treated chickens synthesize and secrete VLDL for at least 48 h in culture. Electron micrographs of these cells reveal more extensive development of the rough endoplasmic reticulum and Golgi complex compared to cells from untreated chickens. Whereas [3H]leucine incorporation into total protein is unaffected by estrogen treatment, [3H]leucine incorporation into cellular and secreted immunoprecipitable VLDL is markedly increased indicating specific activation of VLDL apopeptide synthesis; 8-10% of the labeled protein synthesized and secreted is VLDL. Dodecyl sulfate-acrylamide gel electrophoresis of immunoprecipitated 3H-VLDL reveals three major apopepetides of 300,000, 11,000, and 8,000 daltons corresponding to those of purified chicken VLDL."}
{"id": "PMID:192734", "title": "Estradiol-induced redistribution of lysosomal proteins in rat preputial gland. Evidence from immunologic probes.", "content": "The influence of estrogen on the subcellular localization and distribution of lysosomal components of preputial gland was investigated in the ovariectomized rat. Antisera of high titer and specificity toward high-density lysosomal lipoproteins of this organ were raised in rabbits. The immunologic effectiveness of the IgG fraction so obtained was confirmed by microcomplement fixation, immunodiffusion, and immunoelectrophoresis. By both direct and indirect immunofluorescence techniques, cryostat sections of preputial gland from the control animals exhibited pinpoint cytoplasmic fluorescence, of dimensions corresponding to those of lysosomes. In contrast, specific immunoreactive material in corresponding target cells from animals receiving 0.1 microng of estradiol-17 beta/100 g body wt only 2 min earlier was distributed more homogeneously, indicating release of antigen from the membrane-bounded organelles. Moreover, specific immunofluorescence became evident at cell surfaces and in peri- and supranuclear localization, sites essentially negative in the controls. These effects were intensified at 15 min, as well as by maximal physiologic dose (0.5 microng/100 g body wt) of hormone. The relatively less active epimer, estradiol-17 alpha, exhibited only very limited effectiveness by some of these criteria. These observations, taken together with independent biochemical and ultrastructural evidence, lead to the conclusion that structural labilization of lysosomal constituents and their translocation to the nuclear compartment are early correlates of estrogen action.", "contents": "Estradiol-induced redistribution of lysosomal proteins in rat preputial gland. Evidence from immunologic probes. The influence of estrogen on the subcellular localization and distribution of lysosomal components of preputial gland was investigated in the ovariectomized rat. Antisera of high titer and specificity toward high-density lysosomal lipoproteins of this organ were raised in rabbits. The immunologic effectiveness of the IgG fraction so obtained was confirmed by microcomplement fixation, immunodiffusion, and immunoelectrophoresis. By both direct and indirect immunofluorescence techniques, cryostat sections of preputial gland from the control animals exhibited pinpoint cytoplasmic fluorescence, of dimensions corresponding to those of lysosomes. In contrast, specific immunoreactive material in corresponding target cells from animals receiving 0.1 microng of estradiol-17 beta/100 g body wt only 2 min earlier was distributed more homogeneously, indicating release of antigen from the membrane-bounded organelles. Moreover, specific immunofluorescence became evident at cell surfaces and in peri- and supranuclear localization, sites essentially negative in the controls. These effects were intensified at 15 min, as well as by maximal physiologic dose (0.5 microng/100 g body wt) of hormone. The relatively less active epimer, estradiol-17 alpha, exhibited only very limited effectiveness by some of these criteria. These observations, taken together with independent biochemical and ultrastructural evidence, lead to the conclusion that structural labilization of lysosomal constituents and their translocation to the nuclear compartment are early correlates of estrogen action."}
{"id": "PMID:192735", "title": "Isolation and characterization of the urothelial lumenal plasma membrane.", "content": "The lumenal plasma membrane has been isolated from transitional epithelial cells (urothelium) lining the urinary bladder in sheep by a modified technique involving treatment with hypotonic thioglycolate. The isolated membranes, like those in situ, are distinguished morphologically by arrays of hexagonal particles (in plague regions) separated by smooth interplaque regions. These plaque regions, specifically, can be isolated from the lumenal plasma membrane. Of the proteins constituting the lumenal plasma membrane, five were found to characterize the plaque regions and, in particular, the 33,000-dalton species appears to be most heavily concentrated in the sodium dodecyl sulfate-polyacrylamide gel pattern of the isolated plaque regions. Lipid analyses showed that there are approximately 0.93 mg of phospholipid and 0.27 mg of cholesterol for each milligram of protein, giving a value of 55% lipids and 45% proteins for the composition of the lumenal plasma membrane. The total sialic acid content was measured to be approximately 0.038 micronmol/mg protein for the plasma membrane. Several plasma membrane marker enzymes were found to be associated with the lumenal plasma membrane fraction, but only the 5'-nucleotidase activity was found to be further enriched in the plaque region fraction. Amino acid analysis of the intrinsic proteins of the plaques indicated a polarity index of 45%.", "contents": "Isolation and characterization of the urothelial lumenal plasma membrane. The lumenal plasma membrane has been isolated from transitional epithelial cells (urothelium) lining the urinary bladder in sheep by a modified technique involving treatment with hypotonic thioglycolate. The isolated membranes, like those in situ, are distinguished morphologically by arrays of hexagonal particles (in plague regions) separated by smooth interplaque regions. These plaque regions, specifically, can be isolated from the lumenal plasma membrane. Of the proteins constituting the lumenal plasma membrane, five were found to characterize the plaque regions and, in particular, the 33,000-dalton species appears to be most heavily concentrated in the sodium dodecyl sulfate-polyacrylamide gel pattern of the isolated plaque regions. Lipid analyses showed that there are approximately 0.93 mg of phospholipid and 0.27 mg of cholesterol for each milligram of protein, giving a value of 55% lipids and 45% proteins for the composition of the lumenal plasma membrane. The total sialic acid content was measured to be approximately 0.038 micronmol/mg protein for the plasma membrane. Several plasma membrane marker enzymes were found to be associated with the lumenal plasma membrane fraction, but only the 5'-nucleotidase activity was found to be further enriched in the plaque region fraction. Amino acid analysis of the intrinsic proteins of the plaques indicated a polarity index of 45%."}
{"id": "PMID:192736", "title": "Growth and biochemical characteristics of a detachment variant of CHO cells.", "content": "A variant subline of Chinese hamster cells (line CHO) was isolated that had increased resistance to detachment from the substratum. Comparisons between parental and variant cells of the complex carbohydrates liberated during trypsin detachment showed that the variant cells synthesized little or no hyaluronic acid. These cells also had reduced amounts of other complex carbohydrates in the cell periphery. However, parental and variant cells did not differ in morphology, growth control, or cyclic AMP concentration. Profound changes in the physical nature of the cell periphery, in themselves, evidently are insufficient to cause changes in many aspects of cell behavior.", "contents": "Growth and biochemical characteristics of a detachment variant of CHO cells. A variant subline of Chinese hamster cells (line CHO) was isolated that had increased resistance to detachment from the substratum. Comparisons between parental and variant cells of the complex carbohydrates liberated during trypsin detachment showed that the variant cells synthesized little or no hyaluronic acid. These cells also had reduced amounts of other complex carbohydrates in the cell periphery. However, parental and variant cells did not differ in morphology, growth control, or cyclic AMP concentration. Profound changes in the physical nature of the cell periphery, in themselves, evidently are insufficient to cause changes in many aspects of cell behavior."}
{"id": "PMID:192737", "title": "Comparative studies of glucose-fed and glucose-starved hamster cell cultures: responses in galactose metabolism.", "content": "The metabolic flow of trace amounts of D-[14C]-galactose was followed in cultures of transformed and untransformed hamster cells over a period ranging from five minutes to two hours. The results of chromatographic and enzymatic analyses of the soluble pools are described. Non-glycolytic cells(previously deprived of sugar periods of up to 24 hours) convert D-galactose to galactose-1-phosphate and uridine diphosphoglucuronic acid in 10 to 20 minutes. In the same short assay time, glycolytic cells which have been maintained for 24 hours in media containing glucose or galactose convert D-galactose to uridine diphsphogalactose and uridine diphosphoglucose (ratio 1.4:1). Long term diprivation of sugar also results in 3- to 4-fold increases in the uptake of galactose. In addition, the incorporation of galactose label into chloroformethanol soluble material appears to be influenced by the culture conditions of the untransformed cells while incorporation in the transformed cells appears unaffected. When cycloheximide is included in the maintenance medium for extended periods, the non-glycolytic cells also show increases in galactose uptake rates but the glucose-fed, glycolytic cells llose uptake ability. UDPhexose is the main galactose metabolic peak in the soluble pools of the cycloheximide-treated, glycolytic and the cycloheximide-treated, non-glycolytic cells. The results of these experiments suggests that uptake of galactose and its subsequent metabolism are under separate control.", "contents": "Comparative studies of glucose-fed and glucose-starved hamster cell cultures: responses in galactose metabolism. The metabolic flow of trace amounts of D-[14C]-galactose was followed in cultures of transformed and untransformed hamster cells over a period ranging from five minutes to two hours. The results of chromatographic and enzymatic analyses of the soluble pools are described. Non-glycolytic cells(previously deprived of sugar periods of up to 24 hours) convert D-galactose to galactose-1-phosphate and uridine diphosphoglucuronic acid in 10 to 20 minutes. In the same short assay time, glycolytic cells which have been maintained for 24 hours in media containing glucose or galactose convert D-galactose to uridine diphsphogalactose and uridine diphosphoglucose (ratio 1.4:1). Long term diprivation of sugar also results in 3- to 4-fold increases in the uptake of galactose. In addition, the incorporation of galactose label into chloroformethanol soluble material appears to be influenced by the culture conditions of the untransformed cells while incorporation in the transformed cells appears unaffected. When cycloheximide is included in the maintenance medium for extended periods, the non-glycolytic cells also show increases in galactose uptake rates but the glucose-fed, glycolytic cells llose uptake ability. UDPhexose is the main galactose metabolic peak in the soluble pools of the cycloheximide-treated, glycolytic and the cycloheximide-treated, non-glycolytic cells. The results of these experiments suggests that uptake of galactose and its subsequent metabolism are under separate control."}
{"id": "PMID:192738", "title": "The relative amounts of the cytoplasmic RNA species in normal, transformed and senescent cultured cell lines.", "content": "We have examined the relative quantities of 18S and 28S rRNA, 4S RNA and poly (A) + mRNA in the following cultured cells: the mouse fibroblast lines 3T3 and 3T6 in the resting (contact inhibited) and growing (sparse) states, 3T3 clones transformed with SV40 (SV3T3) and with both SV40 and polyoma SV-Py 3T3), hamster lung fibrobalsts (v79), human cervical carcinoma cells (HeLa), and human diploid fibroblasts at early and late passage. The relative quantities of the RNA species were determined by labeling the cells to equilibrium with 32PO4 and measuring the amount of label in each RNA species. The ratio of mRNA to rRNA varied form 1.1% to 2.7% in the different cell lines, the more rapidly growing cell lines usually giving a higher ratio. In cells experiencing growth limitation either by contact inhibition or due to senescence, the ratio of mRNA to rRNA was about 30% lower than in the corresponding cells in the growing state. In most cell lines the ratio of 4S RNA to 18S rRNA was between 0.8 and 1.2, but in seescent fibroblasts, this ratio increased to greater than 1.7. Senescent fibroblasts also contained much more total RNA per unit of DNA than the same cells at early passage or than 3T6 or 3T3 cells.", "contents": "The relative amounts of the cytoplasmic RNA species in normal, transformed and senescent cultured cell lines. We have examined the relative quantities of 18S and 28S rRNA, 4S RNA and poly (A) + mRNA in the following cultured cells: the mouse fibroblast lines 3T3 and 3T6 in the resting (contact inhibited) and growing (sparse) states, 3T3 clones transformed with SV40 (SV3T3) and with both SV40 and polyoma SV-Py 3T3), hamster lung fibrobalsts (v79), human cervical carcinoma cells (HeLa), and human diploid fibroblasts at early and late passage. The relative quantities of the RNA species were determined by labeling the cells to equilibrium with 32PO4 and measuring the amount of label in each RNA species. The ratio of mRNA to rRNA varied form 1.1% to 2.7% in the different cell lines, the more rapidly growing cell lines usually giving a higher ratio. In cells experiencing growth limitation either by contact inhibition or due to senescence, the ratio of mRNA to rRNA was about 30% lower than in the corresponding cells in the growing state. In most cell lines the ratio of 4S RNA to 18S rRNA was between 0.8 and 1.2, but in seescent fibroblasts, this ratio increased to greater than 1.7. Senescent fibroblasts also contained much more total RNA per unit of DNA than the same cells at early passage or than 3T6 or 3T3 cells."}
{"id": "PMID:192739", "title": "Surface exposure of glycosaminoglycans in resting, growing and virus transformed 3T3 cells.", "content": "Glycosaminoglycans (GAG's) were released by trypsin from the surface of cultured mouse cells (3T3) in two different growing states: during log-growth phase and during resting due to serum starvation. Doubly labelled molecules from resting cells were compared with those from growing as well as from trnsformed cells. Reproducible differences in the elution pattern during ion exchange chromatography and in susceptibility to specific hydrolytic enzymes have been demonstrated: the GAGs pattern of growing normal cells is similar to the pattern of the cells transformed by either Polyoma or SV-40 viruses and very different from the pattern of resting cells. Growing and transformed 3T3 show a relatively low amount of trypsin removable heparan sulphate (HS) and a relatively high amount of hyaluronic acid (HA) while resting cells exhibit an opposite ratio between the two GAG'S. The lowering of HS and the increase of HA in the cell coat is therefore suspected to be more dependent upon growth than upon transformation.", "contents": "Surface exposure of glycosaminoglycans in resting, growing and virus transformed 3T3 cells. Glycosaminoglycans (GAG's) were released by trypsin from the surface of cultured mouse cells (3T3) in two different growing states: during log-growth phase and during resting due to serum starvation. Doubly labelled molecules from resting cells were compared with those from growing as well as from trnsformed cells. Reproducible differences in the elution pattern during ion exchange chromatography and in susceptibility to specific hydrolytic enzymes have been demonstrated: the GAGs pattern of growing normal cells is similar to the pattern of the cells transformed by either Polyoma or SV-40 viruses and very different from the pattern of resting cells. Growing and transformed 3T3 show a relatively low amount of trypsin removable heparan sulphate (HS) and a relatively high amount of hyaluronic acid (HA) while resting cells exhibit an opposite ratio between the two GAG'S. The lowering of HS and the increase of HA in the cell coat is therefore suspected to be more dependent upon growth than upon transformation."}
{"id": "PMID:192740", "title": "Cell cycle changes in transformed cells growing under serum-free conditions.", "content": "Polyoma transformed hamster cells (PyBHK) and SV40 transformed mouse cells (SV3T3) were transferred in culture using crystalline trypsin followed by neutralisation with soybean trypsin inhibitor. Such cells were able to proliferate freely in defined medium without any serum supplement and without any intervening period of adaptation. However, growth rates were reduced under serum-free conditions. Re-establishment of rapid growth rates could be achieved by addition of serum, with the rate attained being proportional to the serum concentration. Irrespective of the prevailing rates of growth, percentages of cells synthesising DNA were the same. However, the rate at which DNA was being synthesised was found to change proportionately with the changes in overall growth rate.", "contents": "Cell cycle changes in transformed cells growing under serum-free conditions. Polyoma transformed hamster cells (PyBHK) and SV40 transformed mouse cells (SV3T3) were transferred in culture using crystalline trypsin followed by neutralisation with soybean trypsin inhibitor. Such cells were able to proliferate freely in defined medium without any serum supplement and without any intervening period of adaptation. However, growth rates were reduced under serum-free conditions. Re-establishment of rapid growth rates could be achieved by addition of serum, with the rate attained being proportional to the serum concentration. Irrespective of the prevailing rates of growth, percentages of cells synthesising DNA were the same. However, the rate at which DNA was being synthesised was found to change proportionately with the changes in overall growth rate."}
{"id": "PMID:192741", "title": "Quantitative recovery of free and esterified fatty acids from thin-layer plates coated with silica gel.", "content": "A method is described for the recovery of fatty acids from silica gel on thin-layer plates. The method is simple and rapid and depends on the conversion of silica gel to potassium silicate, using potassium hydroxide, followed by acidification in such a way that the silicic acid is kept in solution. Fatty acids are then extracted by shaking with solvent. Fatty acid recovery from free fatty acid, phospholipid, glyceride and cholesterol ester zones is more than 90% efficient. There is no oxidation or isomerization of unsaturated fatty acids.", "contents": "Quantitative recovery of free and esterified fatty acids from thin-layer plates coated with silica gel. A method is described for the recovery of fatty acids from silica gel on thin-layer plates. The method is simple and rapid and depends on the conversion of silica gel to potassium silicate, using potassium hydroxide, followed by acidification in such a way that the silicic acid is kept in solution. Fatty acids are then extracted by shaking with solvent. Fatty acid recovery from free fatty acid, phospholipid, glyceride and cholesterol ester zones is more than 90% efficient. There is no oxidation or isomerization of unsaturated fatty acids."}
{"id": "PMID:192744", "title": "Dry column chromatography of phospholipids.", "content": "Separation of common phospholipids can be effected by dry column chromatography on silica gel. The method involves packing the column with dry gel and developing it in solvent mixtures used for thin-layer chromatography of the same lipids. Solvent is allowed to migrate only to the end of the column; access to the bands of separated material is obtained by using columns with a removable glass front. RF values of lipids on development columns and those on thin-layer plates are nearly identical when the column is packed with thin-layer chromatography gel. Such columns, however, develop very slowly. Columns packed with fine silica gel designed for elution column chromatography develop very rapidly and yield separations that are still quite comparable to those obtainable from thin-layer plates. Such columns are convenient for the purification of phospholipids in amounts of 10 mg to about 10 g. Column design and construction are described in detail.", "contents": "Dry column chromatography of phospholipids. Separation of common phospholipids can be effected by dry column chromatography on silica gel. The method involves packing the column with dry gel and developing it in solvent mixtures used for thin-layer chromatography of the same lipids. Solvent is allowed to migrate only to the end of the column; access to the bands of separated material is obtained by using columns with a removable glass front. RF values of lipids on development columns and those on thin-layer plates are nearly identical when the column is packed with thin-layer chromatography gel. Such columns, however, develop very slowly. Columns packed with fine silica gel designed for elution column chromatography develop very rapidly and yield separations that are still quite comparable to those obtainable from thin-layer plates. Such columns are convenient for the purification of phospholipids in amounts of 10 mg to about 10 g. Column design and construction are described in detail."}
{"id": "PMID:192745", "title": "Sequence analysis of synthetic oligonucleotides by high-performance liquid anion-exchange chromatography.", "content": "A simple procedure for the sequential anlysis of small oligonucleotides is reported. The method is based on the simultaneous identification and quantitation of monomers released by venom phosphodiesterase digestion of oligonucleotides using high-performance anion-exchange chromatography on Permaphase AAX at room temperature and by applying isocratic elution conditions. In this way, the correct sequence of five oligomers, e.g., r-ACCUCC, r-CUGUU, r-AGGA, d-ATTACC and d-GGTAAT, could easily be established unambiguously.", "contents": "Sequence analysis of synthetic oligonucleotides by high-performance liquid anion-exchange chromatography. A simple procedure for the sequential anlysis of small oligonucleotides is reported. The method is based on the simultaneous identification and quantitation of monomers released by venom phosphodiesterase digestion of oligonucleotides using high-performance anion-exchange chromatography on Permaphase AAX at room temperature and by applying isocratic elution conditions. In this way, the correct sequence of five oligomers, e.g., r-ACCUCC, r-CUGUU, r-AGGA, d-ATTACC and d-GGTAAT, could easily be established unambiguously."}
{"id": "PMID:192749", "title": "[Determination of indolalkylamines after selective derivatisation (author's transl)].", "content": "The 1N-TMS-omegan-TFA-derivatives of indolalkylamines are suitable for estimation by combined gas chromatography and mass spectrometry for two reasons, viz. (1) Under electron impact charge stabilisation at the indole nucleus is favoured, so structure-specific ions form the base peak. For unsubstituted indoles m/e values of 202 are found and for hydroxyl-substituted indoles m/e values of 290. (2) The calibration curves of the derivatives are linear, even in the femtomole range. The 1N-TMS-omegan-derivatives can easily be obtained by trimethylsilylation with N-methyl-N-trimethylsilyltrifluoroacetamide containing catalytic amounts of N-trimethylsilylimidazole followed by acylation with N-methyl bis(trifluoroacetamide). The serotonin concentrations in different rat tissues are determined by this method of selective omegaN-trifluoroacylation-1N-trimethylsilylation and compared with the values obtained by pertrimethylsilylation.", "contents": "[Determination of indolalkylamines after selective derivatisation (author's transl)]. The 1N-TMS-omegan-TFA-derivatives of indolalkylamines are suitable for estimation by combined gas chromatography and mass spectrometry for two reasons, viz. (1) Under electron impact charge stabilisation at the indole nucleus is favoured, so structure-specific ions form the base peak. For unsubstituted indoles m/e values of 202 are found and for hydroxyl-substituted indoles m/e values of 290. (2) The calibration curves of the derivatives are linear, even in the femtomole range. The 1N-TMS-omegan-derivatives can easily be obtained by trimethylsilylation with N-methyl-N-trimethylsilyltrifluoroacetamide containing catalytic amounts of N-trimethylsilylimidazole followed by acylation with N-methyl bis(trifluoroacetamide). The serotonin concentrations in different rat tissues are determined by this method of selective omegaN-trifluoroacylation-1N-trimethylsilylation and compared with the values obtained by pertrimethylsilylation."}
{"id": "PMID:192750", "title": "Preliminary study of the use of dansyl chloride to determine cyclic-3',5'-AMP in tissues.", "content": "A highly sensitive method for the determination of cyclic-3',5'-AMP has been developed which involves the reaction of the substance with dansyl chloride and the subsequent separation of the dansyl-cyclic-3',5'-AMP derivative by thin-layer chromatography. Experiments with standard solutions of 3H-cyclic-3',5'-AMP have shown that there is a direct relationship between the amount of dansyl-3H-cyclic-3',5'-AMP recovered and that dansylated. The procedure is exceedingly sensitive, allowing milligram quantities of material to be analysed for its endogeneous cyclic-3',5'-AMP content. With the use of 14C-adenine as substrate, this method permits the separation of 14C-cyclic-3',5'-AMP formed from the substrate and other 14C-containing compounds, thus allowing the turn-over of cyclic-3'-5'-AMP to be studied. The usefullness of the method is demonstrated by analysing the turn-over and endogenous content of cyclic-3'-5'-AMP in rat nervous tissue.", "contents": "Preliminary study of the use of dansyl chloride to determine cyclic-3',5'-AMP in tissues. A highly sensitive method for the determination of cyclic-3',5'-AMP has been developed which involves the reaction of the substance with dansyl chloride and the subsequent separation of the dansyl-cyclic-3',5'-AMP derivative by thin-layer chromatography. Experiments with standard solutions of 3H-cyclic-3',5'-AMP have shown that there is a direct relationship between the amount of dansyl-3H-cyclic-3',5'-AMP recovered and that dansylated. The procedure is exceedingly sensitive, allowing milligram quantities of material to be analysed for its endogeneous cyclic-3',5'-AMP content. With the use of 14C-adenine as substrate, this method permits the separation of 14C-cyclic-3',5'-AMP formed from the substrate and other 14C-containing compounds, thus allowing the turn-over of cyclic-3'-5'-AMP to be studied. The usefullness of the method is demonstrated by analysing the turn-over and endogenous content of cyclic-3'-5'-AMP in rat nervous tissue."}
{"id": "PMID:192752", "title": "Identification of a receptor for somatomedin-like polypeptides in human fibroblasts.", "content": "We have demonstrated a specific receptor for somatomedin-like growth polypeptides in human fibroblasts in culture using the closely related polypeptide, multiplication stimulating activity (MSA), as the radioligand. Polypeptides purified from human plasma, somatomedin A and acid soluble nonsuppressible insulin-like activity (NSILA-s), competed potently for 125I-MSA binding, as did unlabeled MSA. Although insulin and proinsulin also strongly inhibited MSA binding, the properties of the growth peptide receptor differed from those of the human fibroblasts insulin receptor. Somatomedin A, NSILA-s, MSA, insulin and proinsulin all stimulated the incorporation of [3H]thymidine into DNA in human fibroblasts. We propose that these polypeptides induce DNA synthesis through their interaction with the growth peptide receptor.", "contents": "Identification of a receptor for somatomedin-like polypeptides in human fibroblasts. We have demonstrated a specific receptor for somatomedin-like growth polypeptides in human fibroblasts in culture using the closely related polypeptide, multiplication stimulating activity (MSA), as the radioligand. Polypeptides purified from human plasma, somatomedin A and acid soluble nonsuppressible insulin-like activity (NSILA-s), competed potently for 125I-MSA binding, as did unlabeled MSA. Although insulin and proinsulin also strongly inhibited MSA binding, the properties of the growth peptide receptor differed from those of the human fibroblasts insulin receptor. Somatomedin A, NSILA-s, MSA, insulin and proinsulin all stimulated the incorporation of [3H]thymidine into DNA in human fibroblasts. We propose that these polypeptides induce DNA synthesis through their interaction with the growth peptide receptor."}
{"id": "PMID:192753", "title": "Reactivity of non-primate growth hormones and prolactins with human growth hormone receptors on cultured human lymphocytes.", "content": "Ovine placental lactogen is as reactive as human growth hormone with the human growth hormone receptor of cultured human (IM-9) lymphocytes, which confirms the findings of Carr and Friesen with receptors of human liver. We now also show that bovine and ovine growth hormones and ovine prolactin have reactivity for the human growth hormone receptor on IM-9 lymphocytes that is of the same order of magnitude (0.03%) as that previously reported for human placental lactogen. The binding studies predict that these non-primate hormones will have biological effects on skeletal growth in primates, either as agonists or antagonists. Previous studies have shown that when IM-9 lymphocytes are exposed to human growth hormone for 18 h at 37 C, there is a time and concentration dependent loss of human growth hormone receptors, and the magnitude of the loss of receptors after preincubation for 18 h at 37 C is greater than the average occupancy of receptors under steady state conditions for 90 min at 30 C. In the present study we show that human and ovine placental lactogens, ovine prolactin, and bovine and ovine growth hormones also produce this effect on the human growth hormone receptor. Since the cellular process by which a hormone induces loss of its own receptors appears to require binding of the hormone to its receptor as well as one or more subsequent steps in hormone action, it is likely that all of the preparations that induce receptor loss will be shown to have some agonist activity of human growth hormone in promoting skeletal growth in primates. Further, these studies extend the interrelationships between primate and non-primate pituitary and placental hormones from what has been suggested previously from biological and structural studies.", "contents": "Reactivity of non-primate growth hormones and prolactins with human growth hormone receptors on cultured human lymphocytes. Ovine placental lactogen is as reactive as human growth hormone with the human growth hormone receptor of cultured human (IM-9) lymphocytes, which confirms the findings of Carr and Friesen with receptors of human liver. We now also show that bovine and ovine growth hormones and ovine prolactin have reactivity for the human growth hormone receptor on IM-9 lymphocytes that is of the same order of magnitude (0.03%) as that previously reported for human placental lactogen. The binding studies predict that these non-primate hormones will have biological effects on skeletal growth in primates, either as agonists or antagonists. Previous studies have shown that when IM-9 lymphocytes are exposed to human growth hormone for 18 h at 37 C, there is a time and concentration dependent loss of human growth hormone receptors, and the magnitude of the loss of receptors after preincubation for 18 h at 37 C is greater than the average occupancy of receptors under steady state conditions for 90 min at 30 C. In the present study we show that human and ovine placental lactogens, ovine prolactin, and bovine and ovine growth hormones also produce this effect on the human growth hormone receptor. Since the cellular process by which a hormone induces loss of its own receptors appears to require binding of the hormone to its receptor as well as one or more subsequent steps in hormone action, it is likely that all of the preparations that induce receptor loss will be shown to have some agonist activity of human growth hormone in promoting skeletal growth in primates. Further, these studies extend the interrelationships between primate and non-primate pituitary and placental hormones from what has been suggested previously from biological and structural studies."}
{"id": "PMID:192754", "title": "MSH/ACTH 4-10 influences behavioral and physiological measures of attention.", "content": "Eleven healthy male volunteers were infused with MSH/ACTH 4-10 and a control solution in a completely crossed and balanced procedure. Perception, attention and memory were tested as were heart rate and cephalic pulse amplitude in response to changes in the environment. Treatment of subjects with MSH/ACTH 4-10 raised their perceptual threshold for detection of simple stimuli and facilitated perceptual integration of patterned information. Administration of the heptapeptide improved the subjects' ability to discriminate tests of relevant from irrelevant information and augmented the heart-rate deceleratory response during presentation of novel stimuli. It was speculated that MSH/ACTH 4-10 has a predominant influence on attentional processes and that it may be uniquely coded for attentional/perceptual functioning.", "contents": "MSH/ACTH 4-10 influences behavioral and physiological measures of attention. Eleven healthy male volunteers were infused with MSH/ACTH 4-10 and a control solution in a completely crossed and balanced procedure. Perception, attention and memory were tested as were heart rate and cephalic pulse amplitude in response to changes in the environment. Treatment of subjects with MSH/ACTH 4-10 raised their perceptual threshold for detection of simple stimuli and facilitated perceptual integration of patterned information. Administration of the heptapeptide improved the subjects' ability to discriminate tests of relevant from irrelevant information and augmented the heart-rate deceleratory response during presentation of novel stimuli. It was speculated that MSH/ACTH 4-10 has a predominant influence on attentional processes and that it may be uniquely coded for attentional/perceptual functioning."}
{"id": "PMID:192755", "title": "HCG binding and stimulation of testosterone biosynthesis in the human fetal testis.", "content": "The role of hCG in the regulation of testicular steroid production in human fetuses from 14 to 20 weeks gestational age was studied. Saturable binding of 125I-hCG to testicular homogenates was demonstrated, and physiologic concentrations of hCG were able to stimulate testosterone formation in testicular minces without the addition of exogenous precursors. In five fetses of 16-20 weeks gestational age, the capacity to bind hCG varied from 25.6 to 42.2 pg/mg wet tissue. The association constant of binding was 1.07+/-0.12 X 10(10) M-1. Testicular minces from six other fetuses (gestational age 14-19 weeks) were incubated in the presence of concentrations of 0, 0.5, 5 or 50 ng/ml NIH-hCG (1 mg=10,000 IU), which are within the physiologic range. Preincubation of 30 min in excess buffer was necessary to observe clear differences in testosterone production rates between controls and hCG stimulated testicular tissues. The greatest increase in testosterone production occurred when the hCG concentration was increased from 0.5 to 5 ng/ml. Little additional stimulation was observed at a concentration of 50 ng/ml. Maximal production rates of up to 12 ng/mg tissue/h were seen. It is concluded that human fetal testes bind hCG, and that physiologic levels of hCG stimulate fetal testicular testosterone formation in vitro at this stage of gestation.", "contents": "HCG binding and stimulation of testosterone biosynthesis in the human fetal testis. The role of hCG in the regulation of testicular steroid production in human fetuses from 14 to 20 weeks gestational age was studied. Saturable binding of 125I-hCG to testicular homogenates was demonstrated, and physiologic concentrations of hCG were able to stimulate testosterone formation in testicular minces without the addition of exogenous precursors. In five fetses of 16-20 weeks gestational age, the capacity to bind hCG varied from 25.6 to 42.2 pg/mg wet tissue. The association constant of binding was 1.07+/-0.12 X 10(10) M-1. Testicular minces from six other fetuses (gestational age 14-19 weeks) were incubated in the presence of concentrations of 0, 0.5, 5 or 50 ng/ml NIH-hCG (1 mg=10,000 IU), which are within the physiologic range. Preincubation of 30 min in excess buffer was necessary to observe clear differences in testosterone production rates between controls and hCG stimulated testicular tissues. The greatest increase in testosterone production occurred when the hCG concentration was increased from 0.5 to 5 ng/ml. Little additional stimulation was observed at a concentration of 50 ng/ml. Maximal production rates of up to 12 ng/mg tissue/h were seen. It is concluded that human fetal testes bind hCG, and that physiologic levels of hCG stimulate fetal testicular testosterone formation in vitro at this stage of gestation."}
{"id": "PMID:192756", "title": "Inactivation of classical and alternative pathway-activated bactericidal activity of human serum by sodium polyanetholsulfonate.", "content": "Sodium polyanetholsulfonate (SPS) at a final concentration of at least 250 microng/ml (0.025%) was required for inhibition of the bactericidal activity of 80% (vol/vol) of fresh human serum against \"promptly serum-sensitive\" strains of Serratia marcescens and control strain Escherichia coli C, i.e., for inhibition of the classical pathway of complement activation. In contrast, SPS at 125 microng/ml (0.0125%) was sufficient for neutralization of the bactericidal activity of 80% (vol/vol) fresh human serum against \"delayed serum-sensitive\" strains of S. marcescens known to activate the alternative pathway of human complement. Addition of up to 500 microng of SPS per ml to 80% (vol/vol) fresh human serum failed to neutralize transferrin-mediated, \"late\" bacteriostasis against control strain E. coli C, an effect that was demonstrable only after prolonged, i.e., overnight, incubation of the test strain. However, this late inhibitory effect against E. coli C was not observed in SPS-treated 20% (vol/vol) fresh human serum or in 10 or 20% (vol/vol) conventionally heat-inactivated human serum. Immunoelectrophoretic examination disclosed that SPS did not precipitate transferrin from either fresh or heat-inactivated human serum. Thus, SPS, at 250 microng/ml, was demonstrated to be sufficient for the inhibition of both classical and alternative complement pathway-activated bactericidal activity of 80% (vol/vol) human serum. However, SPS at a concentration of 500 microng/ml failed to antagonize one antimicrobial system of 80% (vol/vol) human serum, namely transferrin-mediated bacteriostasis.", "contents": "Inactivation of classical and alternative pathway-activated bactericidal activity of human serum by sodium polyanetholsulfonate. Sodium polyanetholsulfonate (SPS) at a final concentration of at least 250 microng/ml (0.025%) was required for inhibition of the bactericidal activity of 80% (vol/vol) of fresh human serum against \"promptly serum-sensitive\" strains of Serratia marcescens and control strain Escherichia coli C, i.e., for inhibition of the classical pathway of complement activation. In contrast, SPS at 125 microng/ml (0.0125%) was sufficient for neutralization of the bactericidal activity of 80% (vol/vol) fresh human serum against \"delayed serum-sensitive\" strains of S. marcescens known to activate the alternative pathway of human complement. Addition of up to 500 microng of SPS per ml to 80% (vol/vol) fresh human serum failed to neutralize transferrin-mediated, \"late\" bacteriostasis against control strain E. coli C, an effect that was demonstrable only after prolonged, i.e., overnight, incubation of the test strain. However, this late inhibitory effect against E. coli C was not observed in SPS-treated 20% (vol/vol) fresh human serum or in 10 or 20% (vol/vol) conventionally heat-inactivated human serum. Immunoelectrophoretic examination disclosed that SPS did not precipitate transferrin from either fresh or heat-inactivated human serum. Thus, SPS, at 250 microng/ml, was demonstrated to be sufficient for the inhibition of both classical and alternative complement pathway-activated bactericidal activity of 80% (vol/vol) human serum. However, SPS at a concentration of 500 microng/ml failed to antagonize one antimicrobial system of 80% (vol/vol) human serum, namely transferrin-mediated bacteriostasis."}
{"id": "PMID:192757", "title": "Infectious causes of equine respiratory disease on Ontario standardbred racetracks.", "content": "Upper respiratory disease has been a serious problem in Standardbred horses on racetracks in Ontario, with outbreaks occurring once or twice annually in late winter and early spring seasons. To determine the causes of these epidemics, a 3-year investigation was carried out in which nasal swabs and serum samples were obtained at intervals from apparently healthy horses and from horses suffering from upper respiratory disease. The nasal swabs were used to isolate bacteria and viruses. The serum samples were examined for the presence and level of antibodies to equine influenza viruses and equine herpesvirus 1. None of the bacteria isolated were associated with the outbreaks of disease. Equine herpesvirus 2 was isolated 72 times from both diseased and apparently healthy horses. Equine herpesvirus 1 was isolated 10 times from horses with respiratory disease, both during and between epidemics. Influenza equine/1 virus was isolated seven times and influenza equine/2 was isolated once during severe outbreaks of upper respiratory disease. Serological evidence confirmed that influenza viruses were the causes of the major epidemics, with the equine/1 strain being involved most often.", "contents": "Infectious causes of equine respiratory disease on Ontario standardbred racetracks. Upper respiratory disease has been a serious problem in Standardbred horses on racetracks in Ontario, with outbreaks occurring once or twice annually in late winter and early spring seasons. To determine the causes of these epidemics, a 3-year investigation was carried out in which nasal swabs and serum samples were obtained at intervals from apparently healthy horses and from horses suffering from upper respiratory disease. The nasal swabs were used to isolate bacteria and viruses. The serum samples were examined for the presence and level of antibodies to equine influenza viruses and equine herpesvirus 1. None of the bacteria isolated were associated with the outbreaks of disease. Equine herpesvirus 2 was isolated 72 times from both diseased and apparently healthy horses. Equine herpesvirus 1 was isolated 10 times from horses with respiratory disease, both during and between epidemics. Influenza equine/1 virus was isolated seven times and influenza equine/2 was isolated once during severe outbreaks of upper respiratory disease. Serological evidence confirmed that influenza viruses were the causes of the major epidemics, with the equine/1 strain being involved most often."}
{"id": "PMID:192758", "title": "Correlation of cytopathic effect, fluorescent-antibody microneutralization, and plaque reduction test results for determining avian infectious bronchitis virus antibodies.", "content": "A microneutralization fluorescent-antibody (MFA) test was effective in determining the level of antibodies to avian infectious bronchitis virus. A comparison of the MFA test with the cytopathic effect microneutralization (MNT) test and 50% plaque reduction (PR) test resulted in positive correlations that were significant (P less than 0.001). The PR test was more sensitive than either the MFA or the MNT test, but there was no significant difference between the sensitivities of the MFA and MNT tests. The MFA test has advantages over the PR test in the capacity to test large numbers of sera in a shorter period of time. The MFA test also can be completed in one-half the time required for the MNT test.", "contents": "Correlation of cytopathic effect, fluorescent-antibody microneutralization, and plaque reduction test results for determining avian infectious bronchitis virus antibodies. A microneutralization fluorescent-antibody (MFA) test was effective in determining the level of antibodies to avian infectious bronchitis virus. A comparison of the MFA test with the cytopathic effect microneutralization (MNT) test and 50% plaque reduction (PR) test resulted in positive correlations that were significant (P less than 0.001). The PR test was more sensitive than either the MFA or the MNT test, but there was no significant difference between the sensitivities of the MFA and MNT tests. The MFA test has advantages over the PR test in the capacity to test large numbers of sera in a shorter period of time. The MFA test also can be completed in one-half the time required for the MNT test."}
{"id": "PMID:192759", "title": "Purification of infectious feline leukemia virus from large volumes of tissue culture fluids.", "content": "Feline leukemia virus from tissue culture fluids was concentrated 100 times by continuous-flow molecular filtration. Virus concentrates retained 100% of their original infectivity. Further purification was accomplished by a single sucrose density gradient centrifugation.", "contents": "Purification of infectious feline leukemia virus from large volumes of tissue culture fluids. Feline leukemia virus from tissue culture fluids was concentrated 100 times by continuous-flow molecular filtration. Virus concentrates retained 100% of their original infectivity. Further purification was accomplished by a single sucrose density gradient centrifugation."}
{"id": "PMID:192760", "title": "Microcalorimetry as a tool for evaluation of blood culture media.", "content": "Evaluation of optimal compositions of blood culture media has called for extensive and laborious work in comparative studies of large series of clincal specimens. Bacterial growth is accompanied by heat production, and calorimetry provides an analytical tool for its detection and quantification. A twin microcalorimeter of the heat conduction type was used to register heat effects in experimentally infected blood cultures. When studying Escherichia coli and Staphylococcus aureus, larger heat effects were produced with 0.05% sodium polyanetholsulfonate than with 600 IU of heparin per ml, which was also the case when using 10% sucrose. The addition of IsoVitaleX (BBL) increased the heat effects produced by the two species mentioned, whereas it had the opposite effect in cultures of Neisseria meningitidis. The present study indicates that microcalorimetry is a valuable and time-saving tool for the evaluation of optimal compositions of bacterial culture media.", "contents": "Microcalorimetry as a tool for evaluation of blood culture media. Evaluation of optimal compositions of blood culture media has called for extensive and laborious work in comparative studies of large series of clincal specimens. Bacterial growth is accompanied by heat production, and calorimetry provides an analytical tool for its detection and quantification. A twin microcalorimeter of the heat conduction type was used to register heat effects in experimentally infected blood cultures. When studying Escherichia coli and Staphylococcus aureus, larger heat effects were produced with 0.05% sodium polyanetholsulfonate than with 600 IU of heparin per ml, which was also the case when using 10% sucrose. The addition of IsoVitaleX (BBL) increased the heat effects produced by the two species mentioned, whereas it had the opposite effect in cultures of Neisseria meningitidis. The present study indicates that microcalorimetry is a valuable and time-saving tool for the evaluation of optimal compositions of bacterial culture media."}
{"id": "PMID:192761", "title": "Effect of dilution on recovery of bacteria from blood.", "content": "The multiplication rate of bacteria in undiluted blood containing sodium polyanethol sulfonate was compared with growth rates obtained in dilutions of blood ranging from 1:2 to 1:8. Although all organisms tested grew in the undiluted blood, increased growth rates were seen in the 1:2 dilution. Further dilution resulted in growth rates equivalent to that obtained with the 1:2 dilution. In view of these results, we question the present recommendations that blood be diluted 1:10 or 1:20.", "contents": "Effect of dilution on recovery of bacteria from blood. The multiplication rate of bacteria in undiluted blood containing sodium polyanethol sulfonate was compared with growth rates obtained in dilutions of blood ranging from 1:2 to 1:8. Although all organisms tested grew in the undiluted blood, increased growth rates were seen in the 1:2 dilution. Further dilution resulted in growth rates equivalent to that obtained with the 1:2 dilution. In view of these results, we question the present recommendations that blood be diluted 1:10 or 1:20."}
{"id": "PMID:192762", "title": "Comparative complement fixation and serum neutralization antibody titers to herpes simplex virus type 1 and Herpesvirus simiae in Macaca mulatta and humans.", "content": "The serological relationship of herpes simplex type 1 virus and Herpesvirus simiae was studied. Antibody titers to these viruses were determined in 163 Macaca mulatta sera and 67 human sera by serum neutralization (SN) and complement fixation (CF) tests. Both groups of sera were also tested by CF with envelope and capsid antigens of herpes simplex type 1. By SN, the majority of the monkeys and all of the humans had a higher titer to herpes simplex type 1 than to H. simiae. By CF, with crude antigens the titers in the monkey sera were greater to H. simiae than to herpes simplex type 1, although four sera had equal titers to both antigens; the titers in the human sera were conversely higher with the herpes simplex type 1 antigen, except for four sera which had equal titers to both antigens. The capsid CF antigen of herpes simplex type 1 was reactive with the human sera but virtually nonreactive with the monkey sera; the envelope CF antigen of herpes simplex type 1 was reactive with both monkey and human sera but was somewhat less reactive than the crude herpes simplex type 1 CF antigen. In addition, serum samples from a patient recently infected with H. simiae were examined by CF and SN for antibody to both herpes simplex type 1 and H. simiae viruses. The serological profile indicated a positive correlation with the infecting virus. Although the SN titers did not conclusively reflect an infection with H. simiae, the CF titers were higher to H. simiae than to herpes simplex in later sera and thus appeared to be compatible with H. simiae infection.", "contents": "Comparative complement fixation and serum neutralization antibody titers to herpes simplex virus type 1 and Herpesvirus simiae in Macaca mulatta and humans. The serological relationship of herpes simplex type 1 virus and Herpesvirus simiae was studied. Antibody titers to these viruses were determined in 163 Macaca mulatta sera and 67 human sera by serum neutralization (SN) and complement fixation (CF) tests. Both groups of sera were also tested by CF with envelope and capsid antigens of herpes simplex type 1. By SN, the majority of the monkeys and all of the humans had a higher titer to herpes simplex type 1 than to H. simiae. By CF, with crude antigens the titers in the monkey sera were greater to H. simiae than to herpes simplex type 1, although four sera had equal titers to both antigens; the titers in the human sera were conversely higher with the herpes simplex type 1 antigen, except for four sera which had equal titers to both antigens. The capsid CF antigen of herpes simplex type 1 was reactive with the human sera but virtually nonreactive with the monkey sera; the envelope CF antigen of herpes simplex type 1 was reactive with both monkey and human sera but was somewhat less reactive than the crude herpes simplex type 1 CF antigen. In addition, serum samples from a patient recently infected with H. simiae were examined by CF and SN for antibody to both herpes simplex type 1 and H. simiae viruses. The serological profile indicated a positive correlation with the infecting virus. Although the SN titers did not conclusively reflect an infection with H. simiae, the CF titers were higher to H. simiae than to herpes simplex in later sera and thus appeared to be compatible with H. simiae infection."}
{"id": "PMID:192763", "title": "The role of 1 alpha, 25-dihydroxyvitamin D in the mediation of intestinal hyperabsorption of calcium in primary hyperparathyroidism and absorptive hypercalciuria.", "content": "The cuase for the intestinal hyperabsorptionof calcium (Ca) in various forms of hypercalciurias was explored by a careful measurement of plasma 1 alpha, 25-dihydroxycholecalciferol [1 alpha, 25-(OH)I D] and by an assessment of intestinal Ca absorption and of parathyroid function. In 18 cases of primary hyperparathyroidism (PHPT), the mean plasma concentration of 1 alpha, 25-(OH)2D was significantly increased (4.9 +/- 2.2 SD ng/dl vs. 3.4 +/- 0.9 ng/dl for the control group), and was significantly correlated with fractional Ca absorption (alpha) (r = 0.80, P less than 0.001). Plasma 1 alpha, 25-(OH)2D was also correlated with urinary Ca (P less than 0.05), but not with serum Ca or phosphorus (P), P clearance, urinary cyclic AMP, or serum immunoreactive parathyroid hormone. In 21 cases of absorptive hypercalciuria (AH), plasma 1 alpha, 25-(OH)2D was elevated in one-third of cases, and the mean value of 4.5 +/- 1.1 ng/dl was significantly higher than that of the control group (P less than 0.01). Since relative hypoparathyroidism may be present, the normal absolute value of plasma 1 alpha, 25-(OH)2D, found in two-thirds of cases of AH, may be considered to be inappropriately high. Moreover, in the majority of cases of AH, the data points relating plasma 1 alpha, 25-(OH)2D and alpha fell within 95% confidence limits of values found in non-AH groups (including PHPT). The results suggest that the intestinal hyperabsorption of Ca in PHPT aw AH may be vitamin D dependent. However, the disturbance in vitamin D metabolism may not be the sole cause for the high Ca absorption in AH, since in some patients with AH, the intestinal Ca absorption appears to be inapp", "contents": "The role of 1 alpha, 25-dihydroxyvitamin D in the mediation of intestinal hyperabsorption of calcium in primary hyperparathyroidism and absorptive hypercalciuria. The cuase for the intestinal hyperabsorptionof calcium (Ca) in various forms of hypercalciurias was explored by a careful measurement of plasma 1 alpha, 25-dihydroxycholecalciferol [1 alpha, 25-(OH)I D] and by an assessment of intestinal Ca absorption and of parathyroid function. In 18 cases of primary hyperparathyroidism (PHPT), the mean plasma concentration of 1 alpha, 25-(OH)2D was significantly increased (4.9 +/- 2.2 SD ng/dl vs. 3.4 +/- 0.9 ng/dl for the control group), and was significantly correlated with fractional Ca absorption (alpha) (r = 0.80, P less than 0.001). Plasma 1 alpha, 25-(OH)2D was also correlated with urinary Ca (P less than 0.05), but not with serum Ca or phosphorus (P), P clearance, urinary cyclic AMP, or serum immunoreactive parathyroid hormone. In 21 cases of absorptive hypercalciuria (AH), plasma 1 alpha, 25-(OH)2D was elevated in one-third of cases, and the mean value of 4.5 +/- 1.1 ng/dl was significantly higher than that of the control group (P less than 0.01). Since relative hypoparathyroidism may be present, the normal absolute value of plasma 1 alpha, 25-(OH)2D, found in two-thirds of cases of AH, may be considered to be inappropriately high. Moreover, in the majority of cases of AH, the data points relating plasma 1 alpha, 25-(OH)2D and alpha fell within 95% confidence limits of values found in non-AH groups (including PHPT). The results suggest that the intestinal hyperabsorption of Ca in PHPT aw AH may be vitamin D dependent. However, the disturbance in vitamin D metabolism may not be the sole cause for the high Ca absorption in AH, since in some patients with AH, the intestinal Ca absorption appears to be inapp"}
{"id": "PMID:192764", "title": "Stimulation of hepatic sodium and potassium-activated adenosine triphosphatase activity by phenobarbital. Its possible role in regulation of bile flow.", "content": "Since phenobarbital administration produces a profound increase in bile flow without changing bile acid secretion, we examined whether this drug increases the activity of hepatic sodium-potassium-activated ATPase [Na+-K+)-ATPase], the postulated regulating enzyme in the secretion of bile salt independent bile flow. After freeze-thawing to increase substrate accessibility, (Na+-K+) ATPase activity was determined by ouabain inhibition of total ATPase activity. Its activity was highest in isolated liver surface membrane fractions enriched in bile canalicult. Phenobarbital administration significatly increased (Na+-K+)-ATPase activity in both liver surface membrane fractions as well as liver homogenates. This enhanced activity is apparently selective for other membrane phosphatases and the enzyme activity in other tissues is either unaltered or decreased. Kinetic analysis of (Ka+-K+)-ATPase indicates that phenobarbital treatment increased maximum velocity and half-maximum activation constant was unchanged, consistent with activation of latent molecules or an increased number of enzyme molecules. The latter process seems more likely because cycloheximide prevented phenobarbital induction and activators were not demonstrated in vitro. Examination of the full time course of phenobarbital induction to determine whether phenobarbital increased synthesis or decreased degradation was consistent with increased synthesis since the apparent degradation rates were similar with or without phenobarbital treatment. The apparent half-life for (Na+-K+)-ATPase was estimated to be approximately 2.5 days, consistent with liver surface membrane protein turnover. The correlation of changes in bile flow with (Na+-K+)-ATPase was examined under several experimental situations. Phenobarbital caused a parallel increase in each during the 1st 2 days of greatment: thereafter other factors become rate limiting for flow, since enzyme activity doesn't reach a new steady state until 4-days. Consistent with increased sodium-potassium exchange, bile sodium was unchanged while potasium concentrations were significantly reduced. Changes in both bile flow and (Na+-K+)-ATPase induced by phenobarbital are independent of thyroid hormone. These studies support the postulate that (Na+-K+)-ATPase is an important factor in regulation of bile flow. In addition, phenobarbital enhancement of both bile flow and (Na+-K+)-ATPase is dependent upon de novo protein synthesis.", "contents": "Stimulation of hepatic sodium and potassium-activated adenosine triphosphatase activity by phenobarbital. Its possible role in regulation of bile flow. Since phenobarbital administration produces a profound increase in bile flow without changing bile acid secretion, we examined whether this drug increases the activity of hepatic sodium-potassium-activated ATPase [Na+-K+)-ATPase], the postulated regulating enzyme in the secretion of bile salt independent bile flow. After freeze-thawing to increase substrate accessibility, (Na+-K+) ATPase activity was determined by ouabain inhibition of total ATPase activity. Its activity was highest in isolated liver surface membrane fractions enriched in bile canalicult. Phenobarbital administration significatly increased (Na+-K+)-ATPase activity in both liver surface membrane fractions as well as liver homogenates. This enhanced activity is apparently selective for other membrane phosphatases and the enzyme activity in other tissues is either unaltered or decreased. Kinetic analysis of (Ka+-K+)-ATPase indicates that phenobarbital treatment increased maximum velocity and half-maximum activation constant was unchanged, consistent with activation of latent molecules or an increased number of enzyme molecules. The latter process seems more likely because cycloheximide prevented phenobarbital induction and activators were not demonstrated in vitro. Examination of the full time course of phenobarbital induction to determine whether phenobarbital increased synthesis or decreased degradation was consistent with increased synthesis since the apparent degradation rates were similar with or without phenobarbital treatment. The apparent half-life for (Na+-K+)-ATPase was estimated to be approximately 2.5 days, consistent with liver surface membrane protein turnover. The correlation of changes in bile flow with (Na+-K+)-ATPase was examined under several experimental situations. Phenobarbital caused a parallel increase in each during the 1st 2 days of greatment: thereafter other factors become rate limiting for flow, since enzyme activity doesn't reach a new steady state until 4-days. Consistent with increased sodium-potassium exchange, bile sodium was unchanged while potasium concentrations were significantly reduced. Changes in both bile flow and (Na+-K+)-ATPase induced by phenobarbital are independent of thyroid hormone. These studies support the postulate that (Na+-K+)-ATPase is an important factor in regulation of bile flow. In addition, phenobarbital enhancement of both bile flow and (Na+-K+)-ATPase is dependent upon de novo protein synthesis."}
{"id": "PMID:192765", "title": "Effects of levamisole on normal and abnormal leukocyte locomotion.", "content": "The anti-helminthic drug levamisole hydrochloride has been reported to stimulate immune responses in humans and experimental animals. We have investigated levamisole effects on human leukocyte locomotion in vitro in studies of neutrophils and mononuclear cells from normal adults, from patients with Chediak-Higashi disease and from patients with the syndrome of hyperimmunoglobulin E, recurrent pyogenic infections, and defective leukocyte chemotaxis. Directed migration (chemotaxis) of neutrophils and mononuclear cells from normal adults and from the hyperimmunoglobulin E syndrome patients, but not from Chediak-Higashi patients, were stimulated by levamisole at concentrations of 0.01-1.0 micronM, with stimulation observed most consistently at 0.1 micronM. These concentrations of drug also increased cyclic GMP levels in mononuclear cells and enhanced hexose monophosphate shunt activity in neutrophils, but did not alter chemotactic factor-induced changes in the surface charge of neutrophils. Other concentrations of levamisole did not affect leukocyte locomotion except for a high concentration (5.0 mM) which stimulated both random and directed leukocyte migration. When patients with the hyperimmunoglobulin E syndrome took levamisole by mouth, the abnormal chemotactic responses of their neutrophils were significantly improved towards normal. These studies are the first to show pharmacologic improvement of in vitro leukocyte locomotion in patients in whom recurrent infections have been attributed to a defect of this leukocyte function.", "contents": "Effects of levamisole on normal and abnormal leukocyte locomotion. The anti-helminthic drug levamisole hydrochloride has been reported to stimulate immune responses in humans and experimental animals. We have investigated levamisole effects on human leukocyte locomotion in vitro in studies of neutrophils and mononuclear cells from normal adults, from patients with Chediak-Higashi disease and from patients with the syndrome of hyperimmunoglobulin E, recurrent pyogenic infections, and defective leukocyte chemotaxis. Directed migration (chemotaxis) of neutrophils and mononuclear cells from normal adults and from the hyperimmunoglobulin E syndrome patients, but not from Chediak-Higashi patients, were stimulated by levamisole at concentrations of 0.01-1.0 micronM, with stimulation observed most consistently at 0.1 micronM. These concentrations of drug also increased cyclic GMP levels in mononuclear cells and enhanced hexose monophosphate shunt activity in neutrophils, but did not alter chemotactic factor-induced changes in the surface charge of neutrophils. Other concentrations of levamisole did not affect leukocyte locomotion except for a high concentration (5.0 mM) which stimulated both random and directed leukocyte migration. When patients with the hyperimmunoglobulin E syndrome took levamisole by mouth, the abnormal chemotactic responses of their neutrophils were significantly improved towards normal. These studies are the first to show pharmacologic improvement of in vitro leukocyte locomotion in patients in whom recurrent infections have been attributed to a defect of this leukocyte function."}
{"id": "PMID:192766", "title": "Enhancement of platelet function by superoxide anion.", "content": "During the aerobic conversion of xanthine to uric acid by xanthine oxidase, superoxide anion and hydrogen peroxide are produced along with the hydroxyl radical. Our studies demonstrate that washed human platelets incubated with xanthine and xanthine oxidase aggregated and released [14C]serotonin. Aggregation and release were dependent on the duration of exposure to xanthine oxidase as well as the concentration of enzyme. Both reactions were inhibited by the superoxide scavenger enzyme superoxide dismutase but not by catalase, or the free radical scavenger mannitol, suggesting that they were induced by superoxide anion. Superoxide-dependent release was inhibited by prior incubation of platelets with 1 mM EDTA, 1 micronM prostaglandin E1, or 1 mM dibutyryl cyclic AMP, but was unaffected by 1 mM acetylsalicylic acid or 1 micronM indomethacin. After prolonged incubation with xanthine and xanthine oxidase there was also efflux of up to 15% of intraplatelet 51Cr, a cytosol marker. This leakage was prevented by the addition of catalase to the media but not by superoxide dismutase. Incubation with xanthine and xanthine oxidase did not produce malonyldialdehyde, the three-carbon fatty acid fragment produced during prostaglandin endoperoxide synthesis and lipid peroxidation. Prior exposure of platelets to low fluxes of superoxide anion lowered the threshold for release by subsequent addition of thrombin, suggesting a synergistic effect. We conclude that superoxide-dependent aggregation and release may be a physiologically important method to modulate hemostatic reactions particularly in areas of inflammation or vessel injury which could have high local concentrations of superoxide anion.", "contents": "Enhancement of platelet function by superoxide anion. During the aerobic conversion of xanthine to uric acid by xanthine oxidase, superoxide anion and hydrogen peroxide are produced along with the hydroxyl radical. Our studies demonstrate that washed human platelets incubated with xanthine and xanthine oxidase aggregated and released [14C]serotonin. Aggregation and release were dependent on the duration of exposure to xanthine oxidase as well as the concentration of enzyme. Both reactions were inhibited by the superoxide scavenger enzyme superoxide dismutase but not by catalase, or the free radical scavenger mannitol, suggesting that they were induced by superoxide anion. Superoxide-dependent release was inhibited by prior incubation of platelets with 1 mM EDTA, 1 micronM prostaglandin E1, or 1 mM dibutyryl cyclic AMP, but was unaffected by 1 mM acetylsalicylic acid or 1 micronM indomethacin. After prolonged incubation with xanthine and xanthine oxidase there was also efflux of up to 15% of intraplatelet 51Cr, a cytosol marker. This leakage was prevented by the addition of catalase to the media but not by superoxide dismutase. Incubation with xanthine and xanthine oxidase did not produce malonyldialdehyde, the three-carbon fatty acid fragment produced during prostaglandin endoperoxide synthesis and lipid peroxidation. Prior exposure of platelets to low fluxes of superoxide anion lowered the threshold for release by subsequent addition of thrombin, suggesting a synergistic effect. We conclude that superoxide-dependent aggregation and release may be a physiologically important method to modulate hemostatic reactions particularly in areas of inflammation or vessel injury which could have high local concentrations of superoxide anion."}
{"id": "PMID:192768", "title": "Antiproliferative effects of 9-beta-d-arabinofuranosyladenine in a mammalian cell line devoid of adenosine deaminase activity.", "content": "The effect of ara-A on cellular growth, DNA synthesis, and RNA synthesis, and RNA synthesis was measured in an established cell line (B-mix K-44/6) devoid of adenosine deaminase activity. Cells adapted to growth in a medium supplemented with horse serum provided an environment totally lacking adenosine deaminase activity whereas cultivation of cells in a medium supplemented with calf serum provided a system capable of deaminating ara-A to ara-H (half-life = 14 hours). Under deaminase-free conditions early log phase cells underwent 1.5 population doublings during 28 hours compared with 0.25 doublings in the presence of 37 micronM ara-A. When cells were grown in medium supplemented with calf serum the additionof 37 to 225 micronM ara-A resulted in a cessation of mitosis for periods of 5 to 30 hours respectively. Following this quiescent period growth resumed at the original rate. With 600 micronM ara-A mitosis was reversibly inhibited up to 35 hours after drug addition. The effects of ara-A on RNA and DNA synthesis were monitored by continuously or pulse labeling B-mix K-44/6 cells with [3H]-uridine or [3H]thymidine. Ara-A did not influence RNA synthesis as judged by labeled uridine incorporation. Under deaminase-free conditions, 5.4 micronM ara-A inhibited labeled thymidine incorporation by 50%. In the presence of the enzyme, approximately twice the ara-A concentration was required for the same inhibition; furthermore the initial inhibition was followed by a partial recovery in the rate of thymidine incorporation. Examination of thymidine incorporation. Examination of thymidine nucleotide pools during ara-A treatment revealed to changes in the labeling of dTMP, dTDP, and dTTP. Thus inhibition of [3H]thymidine incorporation by ara-A accurately reflected inhibition of DNA synthesis. We conclude that, in spite of an initial inhibition of DNA synthesis and mitosis by ara-A, B-mix K-44/6 cells recover from the inhibitory effects if the drug is removed either by a change in the culture medium or by metabolism to ara-H.", "contents": "Antiproliferative effects of 9-beta-d-arabinofuranosyladenine in a mammalian cell line devoid of adenosine deaminase activity. The effect of ara-A on cellular growth, DNA synthesis, and RNA synthesis, and RNA synthesis was measured in an established cell line (B-mix K-44/6) devoid of adenosine deaminase activity. Cells adapted to growth in a medium supplemented with horse serum provided an environment totally lacking adenosine deaminase activity whereas cultivation of cells in a medium supplemented with calf serum provided a system capable of deaminating ara-A to ara-H (half-life = 14 hours). Under deaminase-free conditions early log phase cells underwent 1.5 population doublings during 28 hours compared with 0.25 doublings in the presence of 37 micronM ara-A. When cells were grown in medium supplemented with calf serum the additionof 37 to 225 micronM ara-A resulted in a cessation of mitosis for periods of 5 to 30 hours respectively. Following this quiescent period growth resumed at the original rate. With 600 micronM ara-A mitosis was reversibly inhibited up to 35 hours after drug addition. The effects of ara-A on RNA and DNA synthesis were monitored by continuously or pulse labeling B-mix K-44/6 cells with [3H]-uridine or [3H]thymidine. Ara-A did not influence RNA synthesis as judged by labeled uridine incorporation. Under deaminase-free conditions, 5.4 micronM ara-A inhibited labeled thymidine incorporation by 50%. In the presence of the enzyme, approximately twice the ara-A concentration was required for the same inhibition; furthermore the initial inhibition was followed by a partial recovery in the rate of thymidine incorporation. Examination of thymidine incorporation. Examination of thymidine nucleotide pools during ara-A treatment revealed to changes in the labeling of dTMP, dTDP, and dTTP. Thus inhibition of [3H]thymidine incorporation by ara-A accurately reflected inhibition of DNA synthesis. We conclude that, in spite of an initial inhibition of DNA synthesis and mitosis by ara-A, B-mix K-44/6 cells recover from the inhibitory effects if the drug is removed either by a change in the culture medium or by metabolism to ara-H."}
{"id": "PMID:192769", "title": "Correlation between increased bronchial responsiveness to histamine and diminished plasma cyclic adenosine monophosphate response after epinephrine in asthmatic children. Diminished plasma cyclic adenosine monophosphate response after epinephrine in moderate childhood asthma.", "content": "The respiratory threshold to histamine and the plasma cyclic adenosine monophosphate (AMP) every 5 min for 40 min after subcutaneous epinephrine were determined in 21 children with moderate bronchial asthma who were without symptoms at the time of study. There was a statistically significant correlation between a high respiratory sensitivity to histamine and a low plasma cyclic AMP response to epinephrine. The plasma cyclic AMP response was compared with that in 16 control subjects. The asthmatic patients had significantly diminished responses; the difference was greatest for the values 25 min after stimulation. This study supports the hypotheses that the bronchial hyperresponsiveness in asthma is due partly to a defective beta adrenergic system and that the defect is permanent, existing also during periods without symptoms or medication and in patients with moderate asthma.", "contents": "Correlation between increased bronchial responsiveness to histamine and diminished plasma cyclic adenosine monophosphate response after epinephrine in asthmatic children. Diminished plasma cyclic adenosine monophosphate response after epinephrine in moderate childhood asthma. The respiratory threshold to histamine and the plasma cyclic adenosine monophosphate (AMP) every 5 min for 40 min after subcutaneous epinephrine were determined in 21 children with moderate bronchial asthma who were without symptoms at the time of study. There was a statistically significant correlation between a high respiratory sensitivity to histamine and a low plasma cyclic AMP response to epinephrine. The plasma cyclic AMP response was compared with that in 16 control subjects. The asthmatic patients had significantly diminished responses; the difference was greatest for the values 25 min after stimulation. This study supports the hypotheses that the bronchial hyperresponsiveness in asthma is due partly to a defective beta adrenergic system and that the defect is permanent, existing also during periods without symptoms or medication and in patients with moderate asthma."}
{"id": "PMID:192770", "title": "Comparison of cyclic adenosine monophosphate response of lymphocytes in normal and asthmatic subjects to norepinephrine and salbutamol.", "content": "Reduced response of beta adrenergic receptors, especially beta-2 receptors, has been suggested as a contributing factor in the etiology of asthma. Cyclic adenosine monophosphate (AMP) production in lymphocytes after exposure to 10(-3) M salbutamol, predominantly a beta-2 receptor stimulant, was significantly less in asthmatic subjects than in normal subjects, while there was no significant difference in cyclic AMP response to 10(-3) M norepinephrine, predominantly a beta-1 receptor stimulant. Both drugs evoked the maximum response at 10(-3) M. The cyclic AMP response to salbutamol of 5 asthmatic subjects being treated with steroids was diminished significantly compared with that of 7 patients not treated with steroids; however, the response to norepinephrine was similar in both groups. The degree of the abnormality in the beta-2 receptor response seems to be related to the severity of the asthma.", "contents": "Comparison of cyclic adenosine monophosphate response of lymphocytes in normal and asthmatic subjects to norepinephrine and salbutamol. Reduced response of beta adrenergic receptors, especially beta-2 receptors, has been suggested as a contributing factor in the etiology of asthma. Cyclic adenosine monophosphate (AMP) production in lymphocytes after exposure to 10(-3) M salbutamol, predominantly a beta-2 receptor stimulant, was significantly less in asthmatic subjects than in normal subjects, while there was no significant difference in cyclic AMP response to 10(-3) M norepinephrine, predominantly a beta-1 receptor stimulant. Both drugs evoked the maximum response at 10(-3) M. The cyclic AMP response to salbutamol of 5 asthmatic subjects being treated with steroids was diminished significantly compared with that of 7 patients not treated with steroids; however, the response to norepinephrine was similar in both groups. The degree of the abnormality in the beta-2 receptor response seems to be related to the severity of the asthma."}
{"id": "PMID:192771", "title": "Subsensitivity of beta responses during therapy with a long-acting beta-2 preparation.", "content": "The question whether some tolerance or subsensitivity of various beta receptors develops during therapy with long-acting oral beta-2 agents has practical and theoretical importance. We applied a strong beta-2 stimulus (terbutaline, 5.0 mg orally) at weekly intervals for up to three weeks in 19 stable asthmatics and bronchitics while commencing 5.0 mg terbutaline three times daily. The evening dose was omitted before each morning challenge. Challenges were continued at one and two weeks off terbutaline in some patients to test return of beta function. Patients received no ephedrine for two weeks before the study but were allowed aminophylline or isoproterenol inhalations up to 18 and 4 hr before challenges, respectively. Pulmonary function, pulse, and blood pressure were monitored at 0, 60, 120, and 180 min, and metabolic parameters measured at 0 and 180 min. There was significant drug tolerance in the drop and minimum diastolic pressure reached, rise in lactate, cyclic AMP, and blood glucose, and drop in eosinophils. Peak FEV1 and V50 dropped slightly, but vital capacity and minimal airway resistance did not change significantly. During continuous therapy this slight bronchial subsensitivity is probably obscured by elevated baseline function. It might assume importance during periods of excessive inhaler use or abrupt drug withdrawal.", "contents": "Subsensitivity of beta responses during therapy with a long-acting beta-2 preparation. The question whether some tolerance or subsensitivity of various beta receptors develops during therapy with long-acting oral beta-2 agents has practical and theoretical importance. We applied a strong beta-2 stimulus (terbutaline, 5.0 mg orally) at weekly intervals for up to three weeks in 19 stable asthmatics and bronchitics while commencing 5.0 mg terbutaline three times daily. The evening dose was omitted before each morning challenge. Challenges were continued at one and two weeks off terbutaline in some patients to test return of beta function. Patients received no ephedrine for two weeks before the study but were allowed aminophylline or isoproterenol inhalations up to 18 and 4 hr before challenges, respectively. Pulmonary function, pulse, and blood pressure were monitored at 0, 60, 120, and 180 min, and metabolic parameters measured at 0 and 180 min. There was significant drug tolerance in the drop and minimum diastolic pressure reached, rise in lactate, cyclic AMP, and blood glucose, and drop in eosinophils. Peak FEV1 and V50 dropped slightly, but vital capacity and minimal airway resistance did not change significantly. During continuous therapy this slight bronchial subsensitivity is probably obscured by elevated baseline function. It might assume importance during periods of excessive inhaler use or abrupt drug withdrawal."}
{"id": "PMID:192776", "title": "Aortic medial calcification in progeria-like syndrome.", "content": "Aortic medial calcification was investigated in rats in which the progeria-like syndrome (PLS) was evoked by administering dihydrotachysterol. In 35 experimental rats and 15 controls, calcification was studied morphologically by light and electron microscopy, and by enzyme histochemistry. Body weight, food intake and serum calcium levels were also determined. Calcification occurred along and on the elastic lamellae in association with the accumulation of ground substance. In the smooth-muscle cells surrounding the calcified foci, the activities of various lysosomal enzymes increased concomitantly with a tendency toward transformation of smooth-muscle cells to a modified form. From these observations, the role of ground-substance formation by smooth-muscle cells is postulated, and participation in the catabolism of ground substance by the lysosomal enzymes of these cells is suggested. It appears the increased activity of adenosine monophosphatase should be linked to the calcification. The etiology of weight loss, skin manifestations and aortic calcification in PLS rats seems to be different from that in human progeric diseases. Therefore, the PLS rat should not be readily accepted as an animal model for the study of progeric diseases.", "contents": "Aortic medial calcification in progeria-like syndrome. Aortic medial calcification was investigated in rats in which the progeria-like syndrome (PLS) was evoked by administering dihydrotachysterol. In 35 experimental rats and 15 controls, calcification was studied morphologically by light and electron microscopy, and by enzyme histochemistry. Body weight, food intake and serum calcium levels were also determined. Calcification occurred along and on the elastic lamellae in association with the accumulation of ground substance. In the smooth-muscle cells surrounding the calcified foci, the activities of various lysosomal enzymes increased concomitantly with a tendency toward transformation of smooth-muscle cells to a modified form. From these observations, the role of ground-substance formation by smooth-muscle cells is postulated, and participation in the catabolism of ground substance by the lysosomal enzymes of these cells is suggested. It appears the increased activity of adenosine monophosphatase should be linked to the calcification. The etiology of weight loss, skin manifestations and aortic calcification in PLS rats seems to be different from that in human progeric diseases. Therefore, the PLS rat should not be readily accepted as an animal model for the study of progeric diseases."}
{"id": "PMID:192796", "title": "Immunological study of cytomegalovirus complement-fixing antibodies in the population of the CSR.", "content": "The population from different regions of the CSR was examined serologically for the presence of cytomegalovirus (CMV) antibodies. Exclusively persons showing no signs of disease, chosen by random selection, were examined. The immunological survey was carried out by the complement fixation reaction with CMV antigen prepared in the laboratory from the international strain AD 169. The high incidence found in normal population is suggestive of a considerable dispersion of cytomegalovirus infection. The contact with the virus is followed by antibody response, manifested in most cases only subclinically and asymptomatically. The incidence of CMV antibodies increases with increasing age. In young age groups, antibodies were found in approximately 20%. The number of persons showing positive reactions increased gradually and in the oldest age groups antibodies were found in 70%. The significance of factors causing the incidence of cytomegalovirus antibodies in the population is discussed.", "contents": "Immunological study of cytomegalovirus complement-fixing antibodies in the population of the CSR. The population from different regions of the CSR was examined serologically for the presence of cytomegalovirus (CMV) antibodies. Exclusively persons showing no signs of disease, chosen by random selection, were examined. The immunological survey was carried out by the complement fixation reaction with CMV antigen prepared in the laboratory from the international strain AD 169. The high incidence found in normal population is suggestive of a considerable dispersion of cytomegalovirus infection. The contact with the virus is followed by antibody response, manifested in most cases only subclinically and asymptomatically. The incidence of CMV antibodies increases with increasing age. In young age groups, antibodies were found in approximately 20%. The number of persons showing positive reactions increased gradually and in the oldest age groups antibodies were found in 70%. The significance of factors causing the incidence of cytomegalovirus antibodies in the population is discussed."}
{"id": "PMID:192797", "title": "Effect of concanavalin A on the killing of tumor cells by antibody and complement.", "content": "Concanavalin A (Con A) was found to inhibit the killing of antibody-sensitized line-1 tumor cells (TA) by guinea pig complement (GPC) but not by human complement (HuC). Other plant lectins (wheat germ, leucoagglutinin, and pokeweed mitogen) were also tested but Con A was the only lectin found to inhibit antibody-GPC-mediated killing. The inhibitory effect of Con A was observed when the GPC was mixed with Con A or when the antibody-sensitized cells were pretreated with Con A (TA-Con A) before the addition of GPC. The effect could be reversed by treatment of such cells with alpha-D-methylglucopyranoside or by incubation at 37 degrees C for approximately 2 hr. Con A appeared to act by preventing the binding of the first component of GPC (GPC1) to antibody-sensitized tumor cells. Differences in the binding of the first component of HuC (HuC1) and GPC1 to TA-Con A suggested that a difference in the binding site for HuC1 and GPC1 might exist. There was no difference in the number of GPC1 molecules fixed to antibody-sensitized sheep erythrocytes (EA) or EA treated with Con A in experiments using the same antibody as used with the tumor cells and the same Con A preparation. It would consequently appear that the inhibitory effect of Con A on the binding of GPC1 to TA is not due solely to an interaction of Con A with the antibody.", "contents": "Effect of concanavalin A on the killing of tumor cells by antibody and complement. Concanavalin A (Con A) was found to inhibit the killing of antibody-sensitized line-1 tumor cells (TA) by guinea pig complement (GPC) but not by human complement (HuC). Other plant lectins (wheat germ, leucoagglutinin, and pokeweed mitogen) were also tested but Con A was the only lectin found to inhibit antibody-GPC-mediated killing. The inhibitory effect of Con A was observed when the GPC was mixed with Con A or when the antibody-sensitized cells were pretreated with Con A (TA-Con A) before the addition of GPC. The effect could be reversed by treatment of such cells with alpha-D-methylglucopyranoside or by incubation at 37 degrees C for approximately 2 hr. Con A appeared to act by preventing the binding of the first component of GPC (GPC1) to antibody-sensitized tumor cells. Differences in the binding of the first component of HuC (HuC1) and GPC1 to TA-Con A suggested that a difference in the binding site for HuC1 and GPC1 might exist. There was no difference in the number of GPC1 molecules fixed to antibody-sensitized sheep erythrocytes (EA) or EA treated with Con A in experiments using the same antibody as used with the tumor cells and the same Con A preparation. It would consequently appear that the inhibitory effect of Con A on the binding of GPC1 to TA is not due solely to an interaction of Con A with the antibody."}
{"id": "PMID:192798", "title": "Studies of viral antibody responses among Amish families.", "content": "Serum antibodies to adenovirus (ADN), cytomegalovirus (CMV), herpes simplex virus (HSV), influenza (INF), para-influenza (PAR), mumps (MUM), coxsackie B4 (Cox B4) and B5 (Cox B5) viruses were measured from 584 individuals belonging to 21 Indiana Amish families. Sex and age effects on antibody responses to cytomegalovirus were observed. Age effect on CMV, HSV, INF, PAR, MUM responses were also found. The percentage of responders to some of the viruses was shown to be age dependent, but the levels of antibody response were not affected by the difference in age. A familial basis for the antibody response was demonstrated. Attempts at demonstrating association between HLA haplotypes and responses were not successful. The unlikelihood of predominantly HLA-associated control of viral antibody response was discussed.", "contents": "Studies of viral antibody responses among Amish families. Serum antibodies to adenovirus (ADN), cytomegalovirus (CMV), herpes simplex virus (HSV), influenza (INF), para-influenza (PAR), mumps (MUM), coxsackie B4 (Cox B4) and B5 (Cox B5) viruses were measured from 584 individuals belonging to 21 Indiana Amish families. Sex and age effects on antibody responses to cytomegalovirus were observed. Age effect on CMV, HSV, INF, PAR, MUM responses were also found. The percentage of responders to some of the viruses was shown to be age dependent, but the levels of antibody response were not affected by the difference in age. A familial basis for the antibody response was demonstrated. Attempts at demonstrating association between HLA haplotypes and responses were not successful. The unlikelihood of predominantly HLA-associated control of viral antibody response was discussed."}
{"id": "PMID:192799", "title": "The in vitro effects of histamine and metiamide on neutrophil motility and their relationship to intracellular cyclic nucleotide levels.", "content": "Histamine at concentrations of 1 x 10(-5) M to 5 x 10(-5) M consistently increased neutrophil movement as measured in Boyden chambers. This effect was entirely caused by stimulation of chemokinesis (stimulated random migration) and true chemotaxis was inhibited by these concentrations. This inhibition of chemotaxis could be abolished by pretreatment with metiamide, an H-2 receptor antagonist, and levamisole, but not by diphenylhydramine, an H-1 receptor antagonist. Metiamide at similar concentrations produced a mild stimulation of chemokinesis but has no effect on true chemotaxis. The histamine effects on neutrophil motility were associated with increased levels of intracellular cAMP wehreas cAMP levels were unaffected. Agents known to elevate intracellular cAMP levels produced effects on neutrophil motility similar to those of histamine. It is suggested that histamine exerts a 2-fold effect on neutrophil motility mediated via an H-2 receptor site and associated with elevated levels of cAMP.", "contents": "The in vitro effects of histamine and metiamide on neutrophil motility and their relationship to intracellular cyclic nucleotide levels. Histamine at concentrations of 1 x 10(-5) M to 5 x 10(-5) M consistently increased neutrophil movement as measured in Boyden chambers. This effect was entirely caused by stimulation of chemokinesis (stimulated random migration) and true chemotaxis was inhibited by these concentrations. This inhibition of chemotaxis could be abolished by pretreatment with metiamide, an H-2 receptor antagonist, and levamisole, but not by diphenylhydramine, an H-1 receptor antagonist. Metiamide at similar concentrations produced a mild stimulation of chemokinesis but has no effect on true chemotaxis. The histamine effects on neutrophil motility were associated with increased levels of intracellular cAMP wehreas cAMP levels were unaffected. Agents known to elevate intracellular cAMP levels produced effects on neutrophil motility similar to those of histamine. It is suggested that histamine exerts a 2-fold effect on neutrophil motility mediated via an H-2 receptor site and associated with elevated levels of cAMP."}
{"id": "PMID:192800", "title": "Induction of phenotypic lymphocyte differentiation in LPS unresponsive mice by an LPS-induced serum factor and by lipid A-associated protein.", "content": "Spleen cells from C3H/HeJ mice are known to be unresponsive to mitogenic stimulation by LPS. We show here that T and B cell precursors of C3H/HeJ mice are unresponsive to induction of differentiation by LPS. Phenotypic differentiation of C3H/HeJ lymphocytes can be induced with DB-cAMP, Lipid A-associated protein, and with a serum factor induced by LPS in LPS responder strains.", "contents": "Induction of phenotypic lymphocyte differentiation in LPS unresponsive mice by an LPS-induced serum factor and by lipid A-associated protein. Spleen cells from C3H/HeJ mice are known to be unresponsive to mitogenic stimulation by LPS. We show here that T and B cell precursors of C3H/HeJ mice are unresponsive to induction of differentiation by LPS. Phenotypic differentiation of C3H/HeJ lymphocytes can be induced with DB-cAMP, Lipid A-associated protein, and with a serum factor induced by LPS in LPS responder strains."}
{"id": "PMID:192802", "title": "Relationships between H-2 and viral antigens in murine oncornavirus-induced tumours.", "content": "Cytolytic T lymphocytes (CTL) from murine sarcoma virus (MSV) or Friend leukaemia virus (FLV) inoculated mice lyse syngeneic much more efficiently than allogeneic FMRGi+ lymphoma cells. By comparing the cytolysis of various H-2 different 51Cr lymphomas by CTL from several inbred and congenic lines differing at H-2, and by competition experiments using unlabelled cells, one can demonstrate that this phenomenon is due to an H-2 barrier. H-2b/H-2d hybrid-anti-MSV-CTL immunized by H-2b, H-2d or H-2b/H-2d tumours lyse only FMRGi+ lymphomas of the same H-2, and their activity for a given target is inhibited only by H-2-identical competitive cells. H-2 antigens are therefore directly involved in the interaction between tumour cells and immune CTL which probably react with an 'H-2 modified' antigen of the tumour cells surface. The use of CTL from intra-H-2 recombinant lines shows that H-2D and probably H-2K molecules are involved, but vary according to the tumour cells. A possible role of the I region is discussed as well as the implications of these results in immunosurveillance against viral neoplasia.", "contents": "Relationships between H-2 and viral antigens in murine oncornavirus-induced tumours. Cytolytic T lymphocytes (CTL) from murine sarcoma virus (MSV) or Friend leukaemia virus (FLV) inoculated mice lyse syngeneic much more efficiently than allogeneic FMRGi+ lymphoma cells. By comparing the cytolysis of various H-2 different 51Cr lymphomas by CTL from several inbred and congenic lines differing at H-2, and by competition experiments using unlabelled cells, one can demonstrate that this phenomenon is due to an H-2 barrier. H-2b/H-2d hybrid-anti-MSV-CTL immunized by H-2b, H-2d or H-2b/H-2d tumours lyse only FMRGi+ lymphomas of the same H-2, and their activity for a given target is inhibited only by H-2-identical competitive cells. H-2 antigens are therefore directly involved in the interaction between tumour cells and immune CTL which probably react with an 'H-2 modified' antigen of the tumour cells surface. The use of CTL from intra-H-2 recombinant lines shows that H-2D and probably H-2K molecules are involved, but vary according to the tumour cells. A possible role of the I region is discussed as well as the implications of these results in immunosurveillance against viral neoplasia."}
{"id": "PMID:192803", "title": "Leukocyte and lymphocyte cyclic AMP responses in atopic eczema.", "content": "Lymphocytes from subjects with mild and severe atopic eczema were compared with normal control subjects in regard to their cAMP (3';5'-cyclic adenosine monophosphate) responses to a variety of stimulatory agents. Individuals in the severe eczema group were shown to have a significant diminution in their unstimulated lymphocyte cAMP levels and absolute cAMP responses to 0.5 mM theophylline, 0.5 mM theophyline + 1 micronM epinephrine, 10 mM isoproternol, 1 mM isoproterenol, 10 mM salbutamol, and 3 micron M PGE1. Individuals with mild eczema had a reduced response to 0.5 mM theophylline. The severe eczema groups also differed in a number of these responses from a group of 5 subjects with severe psoriasis. Mixed leukocyte cAMP responses to 10 mM isoproterenol also were examined and found to be diminished in individuals with eczema.", "contents": "Leukocyte and lymphocyte cyclic AMP responses in atopic eczema. Lymphocytes from subjects with mild and severe atopic eczema were compared with normal control subjects in regard to their cAMP (3';5'-cyclic adenosine monophosphate) responses to a variety of stimulatory agents. Individuals in the severe eczema group were shown to have a significant diminution in their unstimulated lymphocyte cAMP levels and absolute cAMP responses to 0.5 mM theophylline, 0.5 mM theophyline + 1 micronM epinephrine, 10 mM isoproternol, 1 mM isoproterenol, 10 mM salbutamol, and 3 micron M PGE1. Individuals with mild eczema had a reduced response to 0.5 mM theophylline. The severe eczema groups also differed in a number of these responses from a group of 5 subjects with severe psoriasis. Mixed leukocyte cAMP responses to 10 mM isoproterenol also were examined and found to be diminished in individuals with eczema."}
{"id": "PMID:192804", "title": "Suppressed response to interferon inducation in mice infected with encephalomyocarditis virus, Semliki forest virus, influenza A2 virus, Herpesvirus hominis type 2, or murine cytomegalovirus.", "content": "Mice infected with encephalomyocarditis virus, Semliki Forest virus, influenza A2 virus, Herpesvirus hominis type 2, or murine cytomegalovirus developed a state of hyporeactivity to interferon induction. In general, the capacity of infected animals to produce interferon in response to inducers became progressively impaired during the course of infection. The severity and time of onset of hyporeactivity, however, were dependent upon the inducer and the nature of the viral infection. During viral infections associated with generalized hyporesponsiveness, a factor that could inhibit interferon production by murine cells in culture was identified in the serum. This serum hyporeactive factor may have mediated the development of hyporeactivity in vivo. Hyporeactivity of the host's interferon response was associated with progression of viral infection and may be partially responsible for the limited effectiveness of interferon inducers in the modification of viral infections, when administered after onset of symptoms.", "contents": "Suppressed response to interferon inducation in mice infected with encephalomyocarditis virus, Semliki forest virus, influenza A2 virus, Herpesvirus hominis type 2, or murine cytomegalovirus. Mice infected with encephalomyocarditis virus, Semliki Forest virus, influenza A2 virus, Herpesvirus hominis type 2, or murine cytomegalovirus developed a state of hyporeactivity to interferon induction. In general, the capacity of infected animals to produce interferon in response to inducers became progressively impaired during the course of infection. The severity and time of onset of hyporeactivity, however, were dependent upon the inducer and the nature of the viral infection. During viral infections associated with generalized hyporesponsiveness, a factor that could inhibit interferon production by murine cells in culture was identified in the serum. This serum hyporeactive factor may have mediated the development of hyporeactivity in vivo. Hyporeactivity of the host's interferon response was associated with progression of viral infection and may be partially responsible for the limited effectiveness of interferon inducers in the modification of viral infections, when administered after onset of symptoms."}
{"id": "PMID:192805", "title": "Genital Herpesvirus homonis infection in mice. II. Treatment with phosphonoacetic acid, adenine arabinoside, and adenine arabinoside 5'-monophosphate.", "content": "Genital infection of mice with Herpesvirus hominis type 2 provides an experimental model for screening potential antiviral chemotherapeutic agents before clinical trials in humans. Intravaginal treatment with phosphonoacetic acid (at a dose of 500 mg/kg in saline or as a 5% cream) initiated 3 hr after inoculation with H. hominis type 2 completely inhibited viral replication in the genital tract and prevented subsequent mortality. Although therapy initiated 24-72 hr after infection significantly reduced titers of virus in vaginal secretions from three- to 100-fold, most mice eventually died of encephalitis. Topical treatment with either adenine arabinoside or adenine arabinoside 5'-monophosphate at a dose of 500 mg/kg in saline or as a 10% cream failed to alter viral replication in the genital tract or to protect the mice from death due to encephalitis. Treatment by the intraperitoneal route with any of these three agents had no effect on local viral replication or final mortality.", "contents": "Genital Herpesvirus homonis infection in mice. II. Treatment with phosphonoacetic acid, adenine arabinoside, and adenine arabinoside 5'-monophosphate. Genital infection of mice with Herpesvirus hominis type 2 provides an experimental model for screening potential antiviral chemotherapeutic agents before clinical trials in humans. Intravaginal treatment with phosphonoacetic acid (at a dose of 500 mg/kg in saline or as a 5% cream) initiated 3 hr after inoculation with H. hominis type 2 completely inhibited viral replication in the genital tract and prevented subsequent mortality. Although therapy initiated 24-72 hr after infection significantly reduced titers of virus in vaginal secretions from three- to 100-fold, most mice eventually died of encephalitis. Topical treatment with either adenine arabinoside or adenine arabinoside 5'-monophosphate at a dose of 500 mg/kg in saline or as a 10% cream failed to alter viral replication in the genital tract or to protect the mice from death due to encephalitis. Treatment by the intraperitoneal route with any of these three agents had no effect on local viral replication or final mortality."}
{"id": "PMID:192806", "title": "Clinical and pathogenetic studies of Medical Lake macaque virus infections in cynomolgus monkeys (simian varicella).", "content": "The Medical Lake macaque (MLM) virus produced varicelliform eruptions in cynomolgus monkeys. Not all experimentally infected monkeys developed overt disease; viremia was found, and specific antibodies were detected. Specific lesions were found in skin, lymph nodes, and spleen. Focal inflammatory lesions were present in liver, pancreas, and lung (after intratracheal instillation of virus). MLM virus was recovered from these and other organs. The temporal movements of MLM virus in and out of primary and secondary target organs remained partially unsolved. MLM virus is related to the Wu strain of varicella virus.", "contents": "Clinical and pathogenetic studies of Medical Lake macaque virus infections in cynomolgus monkeys (simian varicella). The Medical Lake macaque (MLM) virus produced varicelliform eruptions in cynomolgus monkeys. Not all experimentally infected monkeys developed overt disease; viremia was found, and specific antibodies were detected. Specific lesions were found in skin, lymph nodes, and spleen. Focal inflammatory lesions were present in liver, pancreas, and lung (after intratracheal instillation of virus). MLM virus was recovered from these and other organs. The temporal movements of MLM virus in and out of primary and secondary target organs remained partially unsolved. MLM virus is related to the Wu strain of varicella virus."}
{"id": "PMID:192807", "title": "A longitudinal study of varicella-zoster virus infections in renal transplant recipients.", "content": "A serum bank maintained for renal transplant recipients allowed for a longitudinal study of antibody responses before and after herpes zoster. Renal transplant recipients without herpes zoster served as controls. Antibody responses to varicella-zoster virus, herpes simplex virus type 1, and cytomegalovirus were measured. The serological responses following herpes zoster were prompt and sustained (in the majority of cases), transient, or not present at all. Zoster without an eruption occurred (apparent only on retrospective chart review) and furnished an explanation for unexplained unilateral pain syndromes in these patients. Asymptomatic rises in titer of antibody to varicella-zoster virus not explained by rises in antibody to herpes simplex virus occurred in both groups. This latter finding points to an unstable relation between virus and host and supports and hypothesis of Hope-Simpson that subclinical release of virus with resulting antigenic stimulation may maintain immunity to varicella-zoster virus. Patients with herpes zoster and controls did not differ in several humoral immune parameters that might have explained the occurrence of herpes zoster. There was no evidence that herpes zoster precipitated renal graft rejection.", "contents": "A longitudinal study of varicella-zoster virus infections in renal transplant recipients. A serum bank maintained for renal transplant recipients allowed for a longitudinal study of antibody responses before and after herpes zoster. Renal transplant recipients without herpes zoster served as controls. Antibody responses to varicella-zoster virus, herpes simplex virus type 1, and cytomegalovirus were measured. The serological responses following herpes zoster were prompt and sustained (in the majority of cases), transient, or not present at all. Zoster without an eruption occurred (apparent only on retrospective chart review) and furnished an explanation for unexplained unilateral pain syndromes in these patients. Asymptomatic rises in titer of antibody to varicella-zoster virus not explained by rises in antibody to herpes simplex virus occurred in both groups. This latter finding points to an unstable relation between virus and host and supports and hypothesis of Hope-Simpson that subclinical release of virus with resulting antigenic stimulation may maintain immunity to varicella-zoster virus. Patients with herpes zoster and controls did not differ in several humoral immune parameters that might have explained the occurrence of herpes zoster. There was no evidence that herpes zoster precipitated renal graft rejection."}
{"id": "PMID:192808", "title": "Cellular immune responses to herpesviruses during treatment with adenine arabinoside.", "content": "Thirteen patients severely infected with herpesvirus were treated with intravenous adenine arabinoside (ara-A), and two patients received placebo therapy. Blastogenic and cytotoxic responses specific for the virus infecting each patient were determined before, during, and after treatment. Blastogenic responses to three mitogens (phytohemagglutinin, pokeweed, and concanavalin-A) were examined, as were titers of viral antibody. In vitro responses during and after treatment with ara-A were unchanged or often enhanced as compared with values before treatment. Newborn infants, presumably infected at or shortly before birth, did not demonstrate cellular immune reactivity to the infecting virus until after four days of life. In this series of patients, prognosis appeared to be in part determined by the cellular immune competence of the host at the time of infection.", "contents": "Cellular immune responses to herpesviruses during treatment with adenine arabinoside. Thirteen patients severely infected with herpesvirus were treated with intravenous adenine arabinoside (ara-A), and two patients received placebo therapy. Blastogenic and cytotoxic responses specific for the virus infecting each patient were determined before, during, and after treatment. Blastogenic responses to three mitogens (phytohemagglutinin, pokeweed, and concanavalin-A) were examined, as were titers of viral antibody. In vitro responses during and after treatment with ara-A were unchanged or often enhanced as compared with values before treatment. Newborn infants, presumably infected at or shortly before birth, did not demonstrate cellular immune reactivity to the infecting virus until after four days of life. In this series of patients, prognosis appeared to be in part determined by the cellular immune competence of the host at the time of infection."}
{"id": "PMID:192809", "title": "Virological and serological studies of neurological complications of acute hemorrhagic conjunctivitis in Thailand.", "content": "An extensive outbreak of acute hemorrhagic conjunctivitis (AHC) occurred from September to December 1974 in Thailand. At least 29 patients with polio-like motor paralysis that complicated AHC were hospitalized in Bangkok. Paired or triplicate samples of serum from 16 patients were tested for neutralizing antibody to enterovirus type 70 (EV70). A significant rise in titer of antibody was found for two patients, and the other 14 had neutralizing antibody titers ranging from 1:8 to 1:512 without an increasf larger than or equal to 1:16, a level which is considered to be diagnostically significant. Neutralizing antibody to EV70 was detected in 19S fractions of nine sera examined, but neutralizing antibody to three types of poliovirus was confined to 7S fractions. EV70 was isolated from one of seven stool specimens collected on day 37 after the onset of AHC and none of 10 samples of cerebrospinal fluid. These results and additional clinical and epidemiologic findings gave further support to the hypothesis that EV70 infection can cause polio-like motor paralysis as a complication of AHC.", "contents": "Virological and serological studies of neurological complications of acute hemorrhagic conjunctivitis in Thailand. An extensive outbreak of acute hemorrhagic conjunctivitis (AHC) occurred from September to December 1974 in Thailand. At least 29 patients with polio-like motor paralysis that complicated AHC were hospitalized in Bangkok. Paired or triplicate samples of serum from 16 patients were tested for neutralizing antibody to enterovirus type 70 (EV70). A significant rise in titer of antibody was found for two patients, and the other 14 had neutralizing antibody titers ranging from 1:8 to 1:512 without an increasf larger than or equal to 1:16, a level which is considered to be diagnostically significant. Neutralizing antibody to EV70 was detected in 19S fractions of nine sera examined, but neutralizing antibody to three types of poliovirus was confined to 7S fractions. EV70 was isolated from one of seven stool specimens collected on day 37 after the onset of AHC and none of 10 samples of cerebrospinal fluid. These results and additional clinical and epidemiologic findings gave further support to the hypothesis that EV70 infection can cause polio-like motor paralysis as a complication of AHC."}
{"id": "PMID:192810", "title": "Effect of immunization on acute and latent infections of vaginouterine tissue with herpes simplex virus types 1 and 2.", "content": "Inoculation of mice with herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) by the vaginal route resulted in viral shedding during the acute phase of the infection and the development of a latent infection in vaginouterine tissue lasting up to one year in greater than 25% of the animals. Immunization with either serotype of HSV markedly reduced viral shedding when animals were subsequently challenged with the homologous serotype, but immunization with HSV-2 was significantly less effective in preventing the development of a latent infection in the vaginouterine tissue after challenge than was immunization with HSV-1.", "contents": "Effect of immunization on acute and latent infections of vaginouterine tissue with herpes simplex virus types 1 and 2. Inoculation of mice with herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) by the vaginal route resulted in viral shedding during the acute phase of the infection and the development of a latent infection in vaginouterine tissue lasting up to one year in greater than 25% of the animals. Immunization with either serotype of HSV markedly reduced viral shedding when animals were subsequently challenged with the homologous serotype, but immunization with HSV-2 was significantly less effective in preventing the development of a latent infection in the vaginouterine tissue after challenge than was immunization with HSV-1."}
{"id": "PMID:192811", "title": "Immunomodulation of host resistance to experimental viral infections in mice: effects of Corynebacterium acnes, Corynebacterium parvum, and Bacille calmette-gu\u00e9rin.", "content": "Resistance to a representative group of experimental virual infections in mice was significantly enhanced by nonspecific modulation of host defense mechanisms. Corynebacterium acnes, Corynebacterium parvum, and bacille Calmette-Gu\u00e9rin were effective in enhancing host resistance. Animals treated seven to 10 days before inoculation of virus were protected against a lethal infection with Herpesvirus hominis type 2, encephalomyocarditis virus, murine cytomegalovirus, or Semliki Forest virus. The protection of experimental animals against encephalomyocarditis virus infection intitiated by either the intraperitoneal or the respiratory route indicated that C. acnes exerted a systemic, rather than local, effect. A maturation process was required for host defense mechanisms stimulated by C. acnes, as indicated by the failure to enhance resistance in suckling animals. Involvement of cells of the lymphoreticular system was demonstrated by transfer of enhanced resistance against H. hominis type 2 to recipient animals with peritoneal exudate cells harvested from mice pretreated with C. acnes. Finally, these same cells inhibited the progression of herpetic infection in tissue culture. The data suggest that immunomodulation, possibly through activation of macrophages, may offer a method for enhancement of host resistance to viral infections.", "contents": "Immunomodulation of host resistance to experimental viral infections in mice: effects of Corynebacterium acnes, Corynebacterium parvum, and Bacille calmette-gu\u00e9rin. Resistance to a representative group of experimental virual infections in mice was significantly enhanced by nonspecific modulation of host defense mechanisms. Corynebacterium acnes, Corynebacterium parvum, and bacille Calmette-Gu\u00e9rin were effective in enhancing host resistance. Animals treated seven to 10 days before inoculation of virus were protected against a lethal infection with Herpesvirus hominis type 2, encephalomyocarditis virus, murine cytomegalovirus, or Semliki Forest virus. The protection of experimental animals against encephalomyocarditis virus infection intitiated by either the intraperitoneal or the respiratory route indicated that C. acnes exerted a systemic, rather than local, effect. A maturation process was required for host defense mechanisms stimulated by C. acnes, as indicated by the failure to enhance resistance in suckling animals. Involvement of cells of the lymphoreticular system was demonstrated by transfer of enhanced resistance against H. hominis type 2 to recipient animals with peritoneal exudate cells harvested from mice pretreated with C. acnes. Finally, these same cells inhibited the progression of herpetic infection in tissue culture. The data suggest that immunomodulation, possibly through activation of macrophages, may offer a method for enhancement of host resistance to viral infections."}
{"id": "PMID:192812", "title": "Slow virus infection: replication and mechanisms of persistence of visna virus in sheep.", "content": "The influence of the age and immune status of the host on the slow replication and persistence of visna virus in sheep was studied. Twenty-five randomly bred fetal American lambs were inoculated intracerebrally with visna virus. Eight of these fetuses were immunosuppressed by thymectomy and antiserum to lymphocytes before inoculation. Fetuses were sacrificed sequentially, and tissues were processed for viral quantitation. No exponential increase of virus occurred in either the normal or immunosuppressed fetuses, and virus was recovered mainly by explanation of tissues. This finding indicated that the viral genome was present in tissue cells but that the extent of replication in the early phase of infection was restricted by factors unassociated with maturation or immune status of the host. In addition, virus isolated from the peripheral blood leukocytes of a sheep one year after inoculation was antigenically distinct from the plaque-purified virus used for inoculation. This distinction suggested that a major antigenic shift of the agent had occurred and provided another mechanism for the maintenance of the persistent infection.", "contents": "Slow virus infection: replication and mechanisms of persistence of visna virus in sheep. The influence of the age and immune status of the host on the slow replication and persistence of visna virus in sheep was studied. Twenty-five randomly bred fetal American lambs were inoculated intracerebrally with visna virus. Eight of these fetuses were immunosuppressed by thymectomy and antiserum to lymphocytes before inoculation. Fetuses were sacrificed sequentially, and tissues were processed for viral quantitation. No exponential increase of virus occurred in either the normal or immunosuppressed fetuses, and virus was recovered mainly by explanation of tissues. This finding indicated that the viral genome was present in tissue cells but that the extent of replication in the early phase of infection was restricted by factors unassociated with maturation or immune status of the host. In addition, virus isolated from the peripheral blood leukocytes of a sheep one year after inoculation was antigenically distinct from the plaque-purified virus used for inoculation. This distinction suggested that a major antigenic shift of the agent had occurred and provided another mechanism for the maintenance of the persistent infection."}
{"id": "PMID:192813", "title": "Infection and fertilization of mice after artificial insemination with a mixture of sperm and murine cytomegalovirus.", "content": "Female mice were artificially inseminated with a solution of sperm and cytomegalovirus (experimental) or sperm alone (control). Maternal infection was usually induced when virus accompanied sperm at insemination. Fertilization occurred in the presence of virus, and embryogenesis appeared normal on gross examination, although a slight reduction in the number of embryos was observed in the experimental group. Tissue cultures were prepared after gestation for 14 days from individual and pooled embryos. In one of 28 instances, virus was recovered from blind-passaged, experimental, embryonic fibroblasts. All control cultures were negative. This model may prove useful in further study of the pathogenesis of intrauterine cytomegalovirus infection.", "contents": "Infection and fertilization of mice after artificial insemination with a mixture of sperm and murine cytomegalovirus. Female mice were artificially inseminated with a solution of sperm and cytomegalovirus (experimental) or sperm alone (control). Maternal infection was usually induced when virus accompanied sperm at insemination. Fertilization occurred in the presence of virus, and embryogenesis appeared normal on gross examination, although a slight reduction in the number of embryos was observed in the experimental group. Tissue cultures were prepared after gestation for 14 days from individual and pooled embryos. In one of 28 instances, virus was recovered from blind-passaged, experimental, embryonic fibroblasts. All control cultures were negative. This model may prove useful in further study of the pathogenesis of intrauterine cytomegalovirus infection."}
{"id": "PMID:192814", "title": "Transmission and activation of cytomegalovirus with blood transfusion: a mouse model.", "content": "A mouse model that mimics many features of human cytomegalovirus (CMV) infections associated with transfusion and perfusion is described. The concept of antigenic activation of CMV was tested by infusion of blood from latently infected mice, which were found to be virus-negative by tissue culture asssay, into uninfected allogeneic and isogenic hosts. After a latent period, virus was detectable invariably in allogeneic and only rarely in isogenic recipients. Transfusions from uninfected donors into latently infected mice activated CMV in heterologous and homologous recipients. These observations should assist in definition of relevant pathogenetic principles and may explain the failure to recover CMV from healthy human blood donors in spite of predictions of a carrier state based on epidemiologic observations.", "contents": "Transmission and activation of cytomegalovirus with blood transfusion: a mouse model. A mouse model that mimics many features of human cytomegalovirus (CMV) infections associated with transfusion and perfusion is described. The concept of antigenic activation of CMV was tested by infusion of blood from latently infected mice, which were found to be virus-negative by tissue culture asssay, into uninfected allogeneic and isogenic hosts. After a latent period, virus was detectable invariably in allogeneic and only rarely in isogenic recipients. Transfusions from uninfected donors into latently infected mice activated CMV in heterologous and homologous recipients. These observations should assist in definition of relevant pathogenetic principles and may explain the failure to recover CMV from healthy human blood donors in spite of predictions of a carrier state based on epidemiologic observations."}
{"id": "PMID:192815", "title": "Anaerobic bacteria in biliary disease in elderly patients.", "content": "Gallbladder bile from 52 elderly subjects who had undergone biliary tract surgery was examined for the presence of bacteria. Twelve patients had sterile bile, 18 specimens of bile yielded anaerobes as well as aerobes, and 22 yielded aerobic bacteria only. Escherichia coli was the most commonly isolated organism (30 strains). Bacteroides fragilis was the most frequently encountered anaerobic bacterium and was found in 15 patients. The Klebsiella-Enterobacter group was the second most commonly isolated group and B. fragilis was third. Clostridium perfringens was recovered in 10 specimens of bile. Anaerobic bacteria were recovered more frequently in patients with ductal obstruction. The relatively frequent isolation of anaerobes, especially of B. fragilis, in this study may be related to the anaerobic techniques used, to the age of the patients, and to the high incidence of pigment stones among the subjects.", "contents": "Anaerobic bacteria in biliary disease in elderly patients. Gallbladder bile from 52 elderly subjects who had undergone biliary tract surgery was examined for the presence of bacteria. Twelve patients had sterile bile, 18 specimens of bile yielded anaerobes as well as aerobes, and 22 yielded aerobic bacteria only. Escherichia coli was the most commonly isolated organism (30 strains). Bacteroides fragilis was the most frequently encountered anaerobic bacterium and was found in 15 patients. The Klebsiella-Enterobacter group was the second most commonly isolated group and B. fragilis was third. Clostridium perfringens was recovered in 10 specimens of bile. Anaerobic bacteria were recovered more frequently in patients with ductal obstruction. The relatively frequent isolation of anaerobes, especially of B. fragilis, in this study may be related to the anaerobic techniques used, to the age of the patients, and to the high incidence of pigment stones among the subjects."}
{"id": "PMID:192817", "title": "Aquanititave semimicro, semiautomated colorimetric assay for interferon.", "content": "The colorimetric assay for interferon, which utilizes a vital dye uptake for determination of cell viability, was adapted for semimicro quantities of cells and reagents and semiautomated techinques. Factors affecting interferon titer included the duration if interferon treatment of cells prior to viral challenge, the multiplicity of viral challenge, and the number of viral replicative cycles. Only the multiplicity of the volume, of the interferon sample determined final titer, emphasizing that introduction of a volume term in a statement of interferon titer expresses interferon mass. The semimicroassay for interferon in both human and mouse cells proved precise, sensitive, convenient, reliable, and relatively simple and rapid.", "contents": "Aquanititave semimicro, semiautomated colorimetric assay for interferon. The colorimetric assay for interferon, which utilizes a vital dye uptake for determination of cell viability, was adapted for semimicro quantities of cells and reagents and semiautomated techinques. Factors affecting interferon titer included the duration if interferon treatment of cells prior to viral challenge, the multiplicity of viral challenge, and the number of viral replicative cycles. Only the multiplicity of the volume, of the interferon sample determined final titer, emphasizing that introduction of a volume term in a statement of interferon titer expresses interferon mass. The semimicroassay for interferon in both human and mouse cells proved precise, sensitive, convenient, reliable, and relatively simple and rapid."}
{"id": "PMID:192819", "title": "Some experiments on the role of the foetal pituitary in the maturation of the foetal adrenal and the induction of parturition in sheep.", "content": "The effect of repeated increases in plasma ACTH on the production of corticosteroids and androstenedione in the sheep foetus has been investigated. Elevation of foetal plasma ACTH for up to 2 h every 24 h by repeated periods of hypoxia increased the output of cortisol. No consistent effects on foetal or maternal androstenedione concentrations or on maternal oestrogen levels were observed. Repeated short periods of increased foetal plasma ACTH concentration may promote maturation of the foetal adrenal, but there is no increase in androgen secretion by the gland nor is there an increase in oestrogen production by the placenta under such conditions.", "contents": "Some experiments on the role of the foetal pituitary in the maturation of the foetal adrenal and the induction of parturition in sheep. The effect of repeated increases in plasma ACTH on the production of corticosteroids and androstenedione in the sheep foetus has been investigated. Elevation of foetal plasma ACTH for up to 2 h every 24 h by repeated periods of hypoxia increased the output of cortisol. No consistent effects on foetal or maternal androstenedione concentrations or on maternal oestrogen levels were observed. Repeated short periods of increased foetal plasma ACTH concentration may promote maturation of the foetal adrenal, but there is no increase in androgen secretion by the gland nor is there an increase in oestrogen production by the placenta under such conditions."}
{"id": "PMID:192820", "title": "Developmental changes in the responses of the adrenal glands of foetal sheep to endogenous adrenocorticotrophin, as indicated by hormone responses to hypoxaemia.", "content": "The change in plasma ACTH and corticosteroid concentrations in response to a 60 min period of hypoxaemia were studied in foetal and adult sheep during the latter half of pregnancy. Hypoxaemia consistently caused large rises in the concentration of ACTH in foetal plasma, the magnitude of which did not change with gestational age but was related to the physiological state of the foetus. Before 139 days small and slow rises in corticosteroid (predominantly cortisol) concentration in foetal plasma were observed during hypoxaemia, and these may have been of maternal origin. After 139 days, hypoxaemia caused a rapid and large rise in the concentration of cortisol and corticosterone in foetal plasma, which was largely of foetal origin. Hypoxaemia caused no consistent change in maternal plasma ACTH concentration but was associated with progressive increases in plasma cortisol concentrations. The cortisol: corticosterone ratio in foetal plasma was 1-5 before 139 days and increased to 4-1 several days before term which was lower than the value of 9 in maternal plasma. Small concentrations of 11-deoxycortisol and cortisone were detected in maternal and foetal plasma, the changes of which were small during hypoxaemia. The results indicate that a maturational change in the sensitivity of the foetal adrenal to endogenous ACTH occurs several days before term.", "contents": "Developmental changes in the responses of the adrenal glands of foetal sheep to endogenous adrenocorticotrophin, as indicated by hormone responses to hypoxaemia. The change in plasma ACTH and corticosteroid concentrations in response to a 60 min period of hypoxaemia were studied in foetal and adult sheep during the latter half of pregnancy. Hypoxaemia consistently caused large rises in the concentration of ACTH in foetal plasma, the magnitude of which did not change with gestational age but was related to the physiological state of the foetus. Before 139 days small and slow rises in corticosteroid (predominantly cortisol) concentration in foetal plasma were observed during hypoxaemia, and these may have been of maternal origin. After 139 days, hypoxaemia caused a rapid and large rise in the concentration of cortisol and corticosterone in foetal plasma, which was largely of foetal origin. Hypoxaemia caused no consistent change in maternal plasma ACTH concentration but was associated with progressive increases in plasma cortisol concentrations. The cortisol: corticosterone ratio in foetal plasma was 1-5 before 139 days and increased to 4-1 several days before term which was lower than the value of 9 in maternal plasma. Small concentrations of 11-deoxycortisol and cortisone were detected in maternal and foetal plasma, the changes of which were small during hypoxaemia. The results indicate that a maturational change in the sensitivity of the foetal adrenal to endogenous ACTH occurs several days before term."}
{"id": "PMID:192821", "title": "Changes in the concentration of adrenocorticotrophin and corticosteroid in the plasma of foetal sheep in the latter half of pregnancy and during labour.", "content": "The changes in plasma ACTH concentration of pregnant sheep and their foetuses during the latter half of pregnancy and during labour were studied. Before 140 days of gestation the mean concentration in foetal arterial plasma was 117+/-19 (S.E.M.) pg/ml which rose to a mean of 286+/-63 pg/ml. The rise in ACTH occurred at about the same time as, but not before, the rise in corticosteroid concentration in foetal plasma. The maternal plasma ACTH concentration did not change during the latter half of pregnancy and had a mean concentration of 64+/-9 pg/ml. During labour there was a progressive rise in the ACTH concentration in foetal plasma which was not associated with any corticosteroid changes. Ethanol did not suppress labour but reduced the ACTH concentration in foetal plasma.", "contents": "Changes in the concentration of adrenocorticotrophin and corticosteroid in the plasma of foetal sheep in the latter half of pregnancy and during labour. The changes in plasma ACTH concentration of pregnant sheep and their foetuses during the latter half of pregnancy and during labour were studied. Before 140 days of gestation the mean concentration in foetal arterial plasma was 117+/-19 (S.E.M.) pg/ml which rose to a mean of 286+/-63 pg/ml. The rise in ACTH occurred at about the same time as, but not before, the rise in corticosteroid concentration in foetal plasma. The maternal plasma ACTH concentration did not change during the latter half of pregnancy and had a mean concentration of 64+/-9 pg/ml. During labour there was a progressive rise in the ACTH concentration in foetal plasma which was not associated with any corticosteroid changes. Ethanol did not suppress labour but reduced the ACTH concentration in foetal plasma."}
{"id": "PMID:192822", "title": "Control of adrenocorticotrophin secretion by catecholamines in the pregnant and foetal sheep.", "content": "The effect of adrenaline on the maternal and foetal plasma ACTH concentration of twelve pregnant sheep with chronically implanted vascular catheters has been studied. Adrenaline infused into the jugular vein of the ewe or foetus produced carotid arterial adrenaline concentrations of 1-9 ng/ml. The foetal plasma ACTH was 253 +/- 73 pg/ml and it showed a fivefold increase during adrenaline infusion; the ACTH concentration achieved was proportional to the plasma adrenaline. In the ewe plasma ACTH was 99 +/- 23 pg/ml. During adrenaline infusion to the ewe this rose by an amount dependent on the adrenaline concentration achieved and there was also a rise in foetal plasma ACTH but no consistent change in foetal plasma adrenaline. There was no reproducible change in plasma corticosteroid concentration during adrenaline infusion into the foetus but a rise in maternal plasma corticosteroid concentration during infusion into the ewes. Because the adrenaline concentrations achieved during the infusions were within the physiological range, the results indicate that circulating catecholamines may directly or indirectly influence the concentration of ACTH in the circulation. Also, physiological rises in plasma catecholamines in pregnant animals may stimulate the release of ACTH from the foetal pituitary.", "contents": "Control of adrenocorticotrophin secretion by catecholamines in the pregnant and foetal sheep. The effect of adrenaline on the maternal and foetal plasma ACTH concentration of twelve pregnant sheep with chronically implanted vascular catheters has been studied. Adrenaline infused into the jugular vein of the ewe or foetus produced carotid arterial adrenaline concentrations of 1-9 ng/ml. The foetal plasma ACTH was 253 +/- 73 pg/ml and it showed a fivefold increase during adrenaline infusion; the ACTH concentration achieved was proportional to the plasma adrenaline. In the ewe plasma ACTH was 99 +/- 23 pg/ml. During adrenaline infusion to the ewe this rose by an amount dependent on the adrenaline concentration achieved and there was also a rise in foetal plasma ACTH but no consistent change in foetal plasma adrenaline. There was no reproducible change in plasma corticosteroid concentration during adrenaline infusion into the foetus but a rise in maternal plasma corticosteroid concentration during infusion into the ewes. Because the adrenaline concentrations achieved during the infusions were within the physiological range, the results indicate that circulating catecholamines may directly or indirectly influence the concentration of ACTH in the circulation. Also, physiological rises in plasma catecholamines in pregnant animals may stimulate the release of ACTH from the foetal pituitary."}
{"id": "PMID:192825", "title": "Differences between in-vitro and in-vivo potencies of corticotrophins: an interpretation in terms of metabolic stability.", "content": "Relative activities of a series of corticotrophin analogues have been measured by means of five different bioassays using the rat. Similarities in the relative potencies of various ACTH analogues determined using lipolysis or steroidogenesis in vivo and for the lipolytic and steroidogenic responses of fat pads and adrenal slices in vitro emerged and support the concept of a close structural relationship between the ACTH receptors in adipose and adrenal tissues in the rat. Potencies based on the steroidogenic response of isolated adrenal cells, adrenal slices or in-vivo experiments differed markedly from each other. Inactivation of peptides did not occur in the isolated cell assay, so it is likely that this assay estimates potency at the receptor level. A number of arguments suggest that the difference between the isolated cell assay and the other steroidogenic assays lies solely in the effects of peptide inactivation in the latter, and this allows the relative metabolic stabilities for the peptide analogues in these assays to be calculated. In this way it can be shown that: (1) Replacement of L-Ser by D-Ser in amino acid position 1 markedly increases the metabolic stability of the peptide and has only a slight effect on receptor properties. (2) Shortening at the NH2-terminus reduces the activity of peptides at the receptor level by several orders of magnitude, but increases their relative metabolic stability. (3) Introduction of amide groups at the CO2H-terminus markedly increases receptor potency of (1-16), (1-17) and (1-18) ACTH without affecting their metabolic stability in vivo. However, amidation of the CO2H-terminus does have a large effect on metabolic stability in the adrenal slice assay. (4) Replacement of Arg by Lys in positions 17 and 18 of (1-18) ACTH increases potency at the receptor level (adrenal cells) but has little effect on metabolic stability. The comparison of potencies obtained in the various assays, therefore, throws light on the significance of each assay. In addition, the effects of structural modification of analogues can be separately evaluated with respect to the metabolic stability of a peptide and its potency at the receptor level.", "contents": "Differences between in-vitro and in-vivo potencies of corticotrophins: an interpretation in terms of metabolic stability. Relative activities of a series of corticotrophin analogues have been measured by means of five different bioassays using the rat. Similarities in the relative potencies of various ACTH analogues determined using lipolysis or steroidogenesis in vivo and for the lipolytic and steroidogenic responses of fat pads and adrenal slices in vitro emerged and support the concept of a close structural relationship between the ACTH receptors in adipose and adrenal tissues in the rat. Potencies based on the steroidogenic response of isolated adrenal cells, adrenal slices or in-vivo experiments differed markedly from each other. Inactivation of peptides did not occur in the isolated cell assay, so it is likely that this assay estimates potency at the receptor level. A number of arguments suggest that the difference between the isolated cell assay and the other steroidogenic assays lies solely in the effects of peptide inactivation in the latter, and this allows the relative metabolic stabilities for the peptide analogues in these assays to be calculated. In this way it can be shown that: (1) Replacement of L-Ser by D-Ser in amino acid position 1 markedly increases the metabolic stability of the peptide and has only a slight effect on receptor properties. (2) Shortening at the NH2-terminus reduces the activity of peptides at the receptor level by several orders of magnitude, but increases their relative metabolic stability. (3) Introduction of amide groups at the CO2H-terminus markedly increases receptor potency of (1-16), (1-17) and (1-18) ACTH without affecting their metabolic stability in vivo. However, amidation of the CO2H-terminus does have a large effect on metabolic stability in the adrenal slice assay. (4) Replacement of Arg by Lys in positions 17 and 18 of (1-18) ACTH increases potency at the receptor level (adrenal cells) but has little effect on metabolic stability. The comparison of potencies obtained in the various assays, therefore, throws light on the significance of each assay. In addition, the effects of structural modification of analogues can be separately evaluated with respect to the metabolic stability of a peptide and its potency at the receptor level."}
{"id": "PMID:192826", "title": "Induction of melanogenesis in the epidermal melanoblasts of newborn mouse skin by MSH.", "content": "The number of melanocytes positive to the dopa reaction in the epidermis was shown to increase after newborn mice were injected with alpha-MSH or DBc-AMP. The agents seemed to induce the initiation of melanogenesis in the pre-existing melanoblasts. Electron-microscopic observation also demonstrated that alpha-MSH induced not only maturation of melanosomes but also the formation of melanosomes.", "contents": "Induction of melanogenesis in the epidermal melanoblasts of newborn mouse skin by MSH. The number of melanocytes positive to the dopa reaction in the epidermis was shown to increase after newborn mice were injected with alpha-MSH or DBc-AMP. The agents seemed to induce the initiation of melanogenesis in the pre-existing melanoblasts. Electron-microscopic observation also demonstrated that alpha-MSH induced not only maturation of melanosomes but also the formation of melanosomes."}
{"id": "PMID:192827", "title": "Electrical potentials from the eye and optic nerve of Strombus: effects of electrical stimulation of the optic nerve.", "content": "1. Photic stimulation of the mature eye of Strombus can evoke in the optic nerve 'on' activity in numerous small afferent fibres and repetitive 'off' bursts of afferent impulses in a smaller number of larger fibres. 2. Synchronous invasion of the eye by electrically evoked impulses in small optic nerve fibres (apparently the 'on' afferents, antidromically activated) can evoke a burst of impulses in the larger 'off' fibres which propagate away from the eye. Invasion of the eye via one branch of optic nerve can evoke an answering burst in another branch. 3. Such electrically evoked bursts are similar to light-evoked 'off' bursts with respect to their impulse composition, their ability to be inhibited by illumination of the eye, and their susceptibility to MgCl2 anaesthesia. 4. Invasion of the eye by a train of repetitive electrically evoked impulses in the absence of photic stimulation can give rise to repetitive 'off' bursts as well as concomitant oscillatory potentials in the eye which are similar to those normally evoked by cessation of a photic stimulus. 5. The electrically evoked 'off' bursts appear to be caused by an excitatory rebound following the cessation of inhibitory synaptic input from photoreceptors which can be antidromically activated by electrical stimulation of the optic nerve. 6. The experimental results suggest that the rhythmic discharge of the 'off' fibres evoked by the cessation of a photic stimulus is mediated by the abrupt decrease of inhibitory synaptic input from the receptors.", "contents": "Electrical potentials from the eye and optic nerve of Strombus: effects of electrical stimulation of the optic nerve. 1. Photic stimulation of the mature eye of Strombus can evoke in the optic nerve 'on' activity in numerous small afferent fibres and repetitive 'off' bursts of afferent impulses in a smaller number of larger fibres. 2. Synchronous invasion of the eye by electrically evoked impulses in small optic nerve fibres (apparently the 'on' afferents, antidromically activated) can evoke a burst of impulses in the larger 'off' fibres which propagate away from the eye. Invasion of the eye via one branch of optic nerve can evoke an answering burst in another branch. 3. Such electrically evoked bursts are similar to light-evoked 'off' bursts with respect to their impulse composition, their ability to be inhibited by illumination of the eye, and their susceptibility to MgCl2 anaesthesia. 4. Invasion of the eye by a train of repetitive electrically evoked impulses in the absence of photic stimulation can give rise to repetitive 'off' bursts as well as concomitant oscillatory potentials in the eye which are similar to those normally evoked by cessation of a photic stimulus. 5. The electrically evoked 'off' bursts appear to be caused by an excitatory rebound following the cessation of inhibitory synaptic input from photoreceptors which can be antidromically activated by electrical stimulation of the optic nerve. 6. The experimental results suggest that the rhythmic discharge of the 'off' fibres evoked by the cessation of a photic stimulus is mediated by the abrupt decrease of inhibitory synaptic input from the receptors."}
{"id": "PMID:192828", "title": "Lymphocyte surface modulation and cyclic nucleotides I. Topographic correlation of cyclic adenosine 3':5'-monophosphate and immunoglobulin immunofluorescence during lymphocyte capping.", "content": "The cross-linking of human peripheral lymphocyte surface Ig results in an early association of cyclic adenosine 3':5'-monophosphate (cAMP) and the cell surface Ig patches. Examination of the subsequent stages of cap formation reveals the continued relationship of cAMP and the clustered surface Ig. In addition, the generalized influx of calcium produced by the ionophore A-23187 disrupts human lymphocyte caps. During the process of cap dissolution cAMP is still associated with surface Ig. Therefore, it is hypothesized that the localized concentration of cyclic nucleotide and calcium ion regulates the movement of cell surface constituents by coordinating the function of the cell's contractile and structural elements.", "contents": "Lymphocyte surface modulation and cyclic nucleotides I. Topographic correlation of cyclic adenosine 3':5'-monophosphate and immunoglobulin immunofluorescence during lymphocyte capping. The cross-linking of human peripheral lymphocyte surface Ig results in an early association of cyclic adenosine 3':5'-monophosphate (cAMP) and the cell surface Ig patches. Examination of the subsequent stages of cap formation reveals the continued relationship of cAMP and the clustered surface Ig. In addition, the generalized influx of calcium produced by the ionophore A-23187 disrupts human lymphocyte caps. During the process of cap dissolution cAMP is still associated with surface Ig. Therefore, it is hypothesized that the localized concentration of cyclic nucleotide and calcium ion regulates the movement of cell surface constituents by coordinating the function of the cell's contractile and structural elements."}
{"id": "PMID:192829", "title": "Lymphoma in cotton-top marmosets after inoculation with Epstein-Barr virus: tumor incidence, histologic spectrum antibody responses, demonstration of viral DNA, and characterization of viruses.", "content": "6 of 20 cotton-top tamarins (Saguinus oedipus) inoculated with Epstein-Barr virus (EBV) developed diffuse malignant lymphoma resembling reticulum cell or immunoblastic sarcoma of man. Hyperplastic lymphoreticular lesions were induced in three additional animals; in two instances the hyperplastic lesions regressed. Inapparent infection with development of antibody occured in eight animals. In two animals there was no evidence of EBV infection. One animal died in the first week after inoculation of parasitic infection. 10 animals uninoculated or mock-inoculated developed neither lymphoproliferative disease nor antibody. The malignant lymphoma appeared to arise from a cell with an uncleaved vesicular nucleus found in the center of the germinal follicle. The prominent cytologic features of this cell were extensive formation or rough endoplasmic reticulum and elaboration of the cytoplasmic membrane with microvilli. Cell lines derived from these tumors did not have receptors for complement. IgFc, or sheep erythrocytes, and the cell lines adhered to glass and plastic. EB nuclear antigen was found in imprints of two lymph nodes, one with lymphoma and one with hyperplasia. EB virus DNA was detected directly in the tumors of three animals and in cell lines from two lymphomas. Typical herpes virus particles were found in supernatant fluids from cell lines obtained from lymph nodes with tumors and hyperplasia, as well as in lines derived from blood leukocytes of marmosets with inapparent infection. These virus preparations had the biologic property characteristic of EBV, namely, stimulation of cellular DNA synthesis and immortalization of human lymphocytes. The virus derived from two cell lines was neutralized by reference human sera with EBV antibody and not by antibody-negative human sera. The virus derived from the experimental lesions is thus indistinghishable from human EBV. The marmoset has enhanced susceptibility to oncogenesis by EB virus. Among identified factors which may play a role in the heightened tumorigenicity of EB virus in this species are the increased production of virus by transformed cells and the absence of membrane receptors for complement or IgFc on transformed cells.", "contents": "Lymphoma in cotton-top marmosets after inoculation with Epstein-Barr virus: tumor incidence, histologic spectrum antibody responses, demonstration of viral DNA, and characterization of viruses. 6 of 20 cotton-top tamarins (Saguinus oedipus) inoculated with Epstein-Barr virus (EBV) developed diffuse malignant lymphoma resembling reticulum cell or immunoblastic sarcoma of man. Hyperplastic lymphoreticular lesions were induced in three additional animals; in two instances the hyperplastic lesions regressed. Inapparent infection with development of antibody occured in eight animals. In two animals there was no evidence of EBV infection. One animal died in the first week after inoculation of parasitic infection. 10 animals uninoculated or mock-inoculated developed neither lymphoproliferative disease nor antibody. The malignant lymphoma appeared to arise from a cell with an uncleaved vesicular nucleus found in the center of the germinal follicle. The prominent cytologic features of this cell were extensive formation or rough endoplasmic reticulum and elaboration of the cytoplasmic membrane with microvilli. Cell lines derived from these tumors did not have receptors for complement. IgFc, or sheep erythrocytes, and the cell lines adhered to glass and plastic. EB nuclear antigen was found in imprints of two lymph nodes, one with lymphoma and one with hyperplasia. EB virus DNA was detected directly in the tumors of three animals and in cell lines from two lymphomas. Typical herpes virus particles were found in supernatant fluids from cell lines obtained from lymph nodes with tumors and hyperplasia, as well as in lines derived from blood leukocytes of marmosets with inapparent infection. These virus preparations had the biologic property characteristic of EBV, namely, stimulation of cellular DNA synthesis and immortalization of human lymphocytes. The virus derived from two cell lines was neutralized by reference human sera with EBV antibody and not by antibody-negative human sera. The virus derived from the experimental lesions is thus indistinghishable from human EBV. The marmoset has enhanced susceptibility to oncogenesis by EB virus. Among identified factors which may play a role in the heightened tumorigenicity of EB virus in this species are the increased production of virus by transformed cells and the absence of membrane receptors for complement or IgFc on transformed cells."}
{"id": "PMID:192830", "title": "Plasma levels of a viral protein as a diagnostic signal for the presence of mammary tumor: the effect of tumor removal.", "content": "We have previously shown (1, 2) that mice with mammary tumors can always be identified by their very high plasma levels of gp52, a 52,000 mol wt glycoprotein of the mouse mammary tumor virus (MMTV). The present investigation demostrates that the tumor is the principal source of the plasma gp52 since surgical excision is invariably followed in the first 9 days by a sharp decreasing (10-100-fold) of the gp52 levels. Control animals in which the tumors were left in place by a \"sham\" surgical procedure maintained their high level of gp52, which continued to increase as the disease progressed. The behavior of the gp52 after surgical removal suggests that gp52 plasma concentrations are diagnostically and prognostically informative, as indicated by the following finding: (a) All tumor recurrences were correctly diagnosed by increases in gp52 levels, and some were detected 4-7 days before they were found by palpation. (b) Tumor regrowths were accompanied by continued increases in plasma gp52 concentrations at rates that usually matched the speed of tumor development. (c) The only animals that remained tumor free at the termination of the experiment were those that maintained their gp52 levels at or below 15 ng/ml. (d) The probability of a tumor-free animal relapsing within 2 wk is much higher if its gp52 level is above the mean. (e) More remarkably, the plasma levels of gp52 at the time of surgery are superior to the size of the tumors removed as prognostic indicators of eventual surgical \"cures\". The availability of a specific and sensitive systemic measure of disease status should augment the usefulness of the murine mammary tumor model by catalyzing a more rapid acquisition of information on the therapeutic effectiveness of the new and varied drug combinations being tested for adjuvant chemotherapy.", "contents": "Plasma levels of a viral protein as a diagnostic signal for the presence of mammary tumor: the effect of tumor removal. We have previously shown (1, 2) that mice with mammary tumors can always be identified by their very high plasma levels of gp52, a 52,000 mol wt glycoprotein of the mouse mammary tumor virus (MMTV). The present investigation demostrates that the tumor is the principal source of the plasma gp52 since surgical excision is invariably followed in the first 9 days by a sharp decreasing (10-100-fold) of the gp52 levels. Control animals in which the tumors were left in place by a \"sham\" surgical procedure maintained their high level of gp52, which continued to increase as the disease progressed. The behavior of the gp52 after surgical removal suggests that gp52 plasma concentrations are diagnostically and prognostically informative, as indicated by the following finding: (a) All tumor recurrences were correctly diagnosed by increases in gp52 levels, and some were detected 4-7 days before they were found by palpation. (b) Tumor regrowths were accompanied by continued increases in plasma gp52 concentrations at rates that usually matched the speed of tumor development. (c) The only animals that remained tumor free at the termination of the experiment were those that maintained their gp52 levels at or below 15 ng/ml. (d) The probability of a tumor-free animal relapsing within 2 wk is much higher if its gp52 level is above the mean. (e) More remarkably, the plasma levels of gp52 at the time of surgery are superior to the size of the tumors removed as prognostic indicators of eventual surgical \"cures\". The availability of a specific and sensitive systemic measure of disease status should augment the usefulness of the murine mammary tumor model by catalyzing a more rapid acquisition of information on the therapeutic effectiveness of the new and varied drug combinations being tested for adjuvant chemotherapy."}
{"id": "PMID:192831", "title": "Changes in cyclic GMP levels during forelimb regeneration in adult Notophthalmus viridescens.", "content": "Cyclic 3', 5'-guanosine monophosphate (cGMP) was measured at eight stages of forelimb regeneration in adult newts and compared with the cGMP levels of non-regenerating control limbs. There was a significant increase in cGMP content during dedifferentiation followed by a sharp decrease to minimal levels at the cone stage. A second smaller increase in cGMP occurred between the cone stage and mid-differentiation, followed by a decrease to relatively constant levels approaching control values as differentiation progressed. The changes in cGMP during dedifferentiation and during the period of highest cell proliferation indicate that cGMP may play a role in these processes. The smaller increases in cGMP levels during differentiation may reflect a reduced rate of cell division in the differentiating tissues.", "contents": "Changes in cyclic GMP levels during forelimb regeneration in adult Notophthalmus viridescens. Cyclic 3', 5'-guanosine monophosphate (cGMP) was measured at eight stages of forelimb regeneration in adult newts and compared with the cGMP levels of non-regenerating control limbs. There was a significant increase in cGMP content during dedifferentiation followed by a sharp decrease to minimal levels at the cone stage. A second smaller increase in cGMP occurred between the cone stage and mid-differentiation, followed by a decrease to relatively constant levels approaching control values as differentiation progressed. The changes in cGMP during dedifferentiation and during the period of highest cell proliferation indicate that cGMP may play a role in these processes. The smaller increases in cGMP levels during differentiation may reflect a reduced rate of cell division in the differentiating tissues."}
{"id": "PMID:192832", "title": "The effect of sodium chloride and NADH on the growth of six strains of haemophilus species pathogenic to chickens.", "content": "Six strains of Haemophilus species, pathogenic to chickens, required 1-0 to 1-5% (w/v) NaCl for optimum growth. The requirement was for Na+ rather than NaCl. A sodium salt buffer influenced the optimum NaCl requirement and enhanced growth. Each strain required a different concentration of NADH for an optimum rate of growth.", "contents": "The effect of sodium chloride and NADH on the growth of six strains of haemophilus species pathogenic to chickens. Six strains of Haemophilus species, pathogenic to chickens, required 1-0 to 1-5% (w/v) NaCl for optimum growth. The requirement was for Na+ rather than NaCl. A sodium salt buffer influenced the optimum NaCl requirement and enhanced growth. Each strain required a different concentration of NADH for an optimum rate of growth."}
{"id": "PMID:192833", "title": "Expression of Klebsiella nif and his genes in Salmonella typhimurium.", "content": "Derivatives of Salmonella typhimurium carrying F prime or P prime plasmids with Klebsiella nif and his genes had specific nitrogenase activities similar to Klebsiella in selective conditions, even to showing \"hyperinduction\" under argon. No evidence was obtained for catabolite repression of normal nif expression but dibutyl cyclic AMP often augmented \"hyperinduction\". In non-selective conditions the Klebsiella his nif determinants were rapidly lost from the plasmids; the low levels of nif expression and temperature-sensitive his expression previously reported were probably due to ready loss of his nif in the test conditions used.", "contents": "Expression of Klebsiella nif and his genes in Salmonella typhimurium. Derivatives of Salmonella typhimurium carrying F prime or P prime plasmids with Klebsiella nif and his genes had specific nitrogenase activities similar to Klebsiella in selective conditions, even to showing \"hyperinduction\" under argon. No evidence was obtained for catabolite repression of normal nif expression but dibutyl cyclic AMP often augmented \"hyperinduction\". In non-selective conditions the Klebsiella his nif determinants were rapidly lost from the plasmids; the low levels of nif expression and temperature-sensitive his expression previously reported were probably due to ready loss of his nif in the test conditions used."}
{"id": "PMID:192834", "title": "Induction of Marek's disease virus antigens by IdUrd in a chicken lymphoblastoid cell line.", "content": "Marek's disease virus (MDV) antigens, as detected by immunofluorescence, were induced in a lymphoblastoid cell line, MSB-I, in the presence of IdUrd. When treated with 20 microng/ml of IdUrd there was no increase in the number of cells producing virus particles. If IdUrd was removed, an increase in virus production followed. Activation of the MDV genome appeared to require incorporation of IdUrd into cellular DNA and occurred during the first 12 h of culture. Expression of the activated genome required de novo protein synthesis and occurred during the next 12 h. The MDV genome in high producer MSB-I cells could be activated with low concentrations of IdUrd, whereas low producer MSB-I cells could not be activated with IdUrd to any great extent.", "contents": "Induction of Marek's disease virus antigens by IdUrd in a chicken lymphoblastoid cell line. Marek's disease virus (MDV) antigens, as detected by immunofluorescence, were induced in a lymphoblastoid cell line, MSB-I, in the presence of IdUrd. When treated with 20 microng/ml of IdUrd there was no increase in the number of cells producing virus particles. If IdUrd was removed, an increase in virus production followed. Activation of the MDV genome appeared to require incorporation of IdUrd into cellular DNA and occurred during the first 12 h of culture. Expression of the activated genome required de novo protein synthesis and occurred during the next 12 h. The MDV genome in high producer MSB-I cells could be activated with low concentrations of IdUrd, whereas low producer MSB-I cells could not be activated with IdUrd to any great extent."}
{"id": "PMID:192835", "title": "Comparison of the polypeptides of several strains of human cytomegalovirus.", "content": "Analysis of purified human cytomegalovirus (CMV) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed 32 polypeptides with mol. wt. ranging from 13,500 to 235,000. Similar analysis of purified preparations of four strains of CMV showed a remarkable similarity in polypeptide composition. Results indicate that the four strains may be related.", "contents": "Comparison of the polypeptides of several strains of human cytomegalovirus. Analysis of purified human cytomegalovirus (CMV) by sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed 32 polypeptides with mol. wt. ranging from 13,500 to 235,000. Similar analysis of purified preparations of four strains of CMV showed a remarkable similarity in polypeptide composition. Results indicate that the four strains may be related."}
{"id": "PMID:192836", "title": "Differences in the physical properties of dense and standard poliovirus particles.", "content": "Dense poliovirus particles (DP) differ in buoyant density, sedimentation coefficient and lability from standard poliovirus particles. Dense particles band at a density of 1-44 g/ml in isopycnic CsCl gradients and sediment in sucrose gradients at 220S. However, when DP are centrifuged in sucrose gradients containing 1-5 M-KCl, NaCl or LiCl, two types of particles are observed, one sedimenting at 220S and the other at 160S. Particles sedimenting at 220S are converted into particles sedimenting at 160S by incubation at 37 degrees C in 1-5 M-KCl. The high buoyant density seems to be correlated with the high lability of DP. Dense particles are extremely labile in isotonic phosphate-buffered saline. Their degradation proceeds through an RNA-containing particle lacking polypeptide VP4, to RNA and empty capsids.", "contents": "Differences in the physical properties of dense and standard poliovirus particles. Dense poliovirus particles (DP) differ in buoyant density, sedimentation coefficient and lability from standard poliovirus particles. Dense particles band at a density of 1-44 g/ml in isopycnic CsCl gradients and sediment in sucrose gradients at 220S. However, when DP are centrifuged in sucrose gradients containing 1-5 M-KCl, NaCl or LiCl, two types of particles are observed, one sedimenting at 220S and the other at 160S. Particles sedimenting at 220S are converted into particles sedimenting at 160S by incubation at 37 degrees C in 1-5 M-KCl. The high buoyant density seems to be correlated with the high lability of DP. Dense particles are extremely labile in isotonic phosphate-buffered saline. Their degradation proceeds through an RNA-containing particle lacking polypeptide VP4, to RNA and empty capsids."}
{"id": "PMID:192837", "title": "Electron microscopy of herpes simplex virus DNA molecules isolated from infected cells by centrifugation in CsCl density gradients.", "content": "Herpes simplex virus (HSV) DNA molecules were isolated from infected BSC 1 cells and centrifuged in CsCl-ethidium bromide density gradients. Both newly labelled and mature virus DNA molecules were found to have a linear conformation. The morphology of virus DNA molecules at different stages of the virus growth cycle in BSC 1 cells, was studied by electron microscopy after separation of virus DNA from cellular DNA by centrifugation in CsCl gradients. In each sample, about 200 virus DNA molecules were photographed and the different morphological forms were studied. Four classes of virus DNA molecules were observed: (a) mature linear DNA molecules, 52-4 +/- 3-3 micronm in length, (b) DNA intermediates, (c) virus DNA molecules having one or more single-stranded filaments attached to them and (d) molecules with collapsed regions or with branches. A few circular molecules as well as linear DNA molecules longer than unit length were also observed. The virus DNA molecules resembling replicative intermediates gradually increased in number and reached a maximal amount of about 5% of the virus DNA population at 12 h after infection. The other forms of virus DNA were found to persist after the number of replicating DNA molecules decreased.", "contents": "Electron microscopy of herpes simplex virus DNA molecules isolated from infected cells by centrifugation in CsCl density gradients. Herpes simplex virus (HSV) DNA molecules were isolated from infected BSC 1 cells and centrifuged in CsCl-ethidium bromide density gradients. Both newly labelled and mature virus DNA molecules were found to have a linear conformation. The morphology of virus DNA molecules at different stages of the virus growth cycle in BSC 1 cells, was studied by electron microscopy after separation of virus DNA from cellular DNA by centrifugation in CsCl gradients. In each sample, about 200 virus DNA molecules were photographed and the different morphological forms were studied. Four classes of virus DNA molecules were observed: (a) mature linear DNA molecules, 52-4 +/- 3-3 micronm in length, (b) DNA intermediates, (c) virus DNA molecules having one or more single-stranded filaments attached to them and (d) molecules with collapsed regions or with branches. A few circular molecules as well as linear DNA molecules longer than unit length were also observed. The virus DNA molecules resembling replicative intermediates gradually increased in number and reached a maximal amount of about 5% of the virus DNA population at 12 h after infection. The other forms of virus DNA were found to persist after the number of replicating DNA molecules decreased."}
{"id": "PMID:192838", "title": "Lipids of transmissible gastroenteritis virus and their relation to those of two different host cells.", "content": "The lipids of two cell types (primary pig kidney and secondary adult pig thyroid) and those of transmissible gastroenteritis virus (TGEV) grown in these cells were studied using 14C-palmitic acid. Differences were demonstrated between the incorporation of isotopically labelled lipid precursors in the two cell types and it was found that the phospholipid and glycolipid profiles of purified TGEV closely resembled those of the host cell in which it was grown.", "contents": "Lipids of transmissible gastroenteritis virus and their relation to those of two different host cells. The lipids of two cell types (primary pig kidney and secondary adult pig thyroid) and those of transmissible gastroenteritis virus (TGEV) grown in these cells were studied using 14C-palmitic acid. Differences were demonstrated between the incorporation of isotopically labelled lipid precursors in the two cell types and it was found that the phospholipid and glycolipid profiles of purified TGEV closely resembled those of the host cell in which it was grown."}
{"id": "PMID:192839", "title": "Effects of ouabain on the anticellular and antiviral activities of human and mouse interferon.", "content": "When transformed human embryonic cells, RSa and RSb, were treated for 48 h with both 10(-7) M-ouabain and 1000 units/ml of human leucocyte inteferon, there was an additive suppression of cell growth. In contrast, the antiviral action of the human interferon was inhibited by this concentration of ouabain. Similar effects of combined treatment with interferon and ouabain were found with IFr cells (which are relatively resistant to the anticellular effect of interferon), and with mouse cells of the K3b line.", "contents": "Effects of ouabain on the anticellular and antiviral activities of human and mouse interferon. When transformed human embryonic cells, RSa and RSb, were treated for 48 h with both 10(-7) M-ouabain and 1000 units/ml of human leucocyte inteferon, there was an additive suppression of cell growth. In contrast, the antiviral action of the human interferon was inhibited by this concentration of ouabain. Similar effects of combined treatment with interferon and ouabain were found with IFr cells (which are relatively resistant to the anticellular effect of interferon), and with mouse cells of the K3b line."}
{"id": "PMID:192840", "title": "Genetic control of resistance to subgroup A and subgroup C tumour viruses in Rhode Island Red fowl: evidence for linkage between the tumour virus a (tva) and tumour virus c (tvc) loci.", "content": "A study, using the Rhode Island Red (RIR) strain of fowl maintained at Houghton Poultry Research Station, was made to investigate the genetic control of cellular response to infection with viruses of subgroups A and C. Family matings within the RIR strain and test-crosses between the RIR parents and White Leghorn (WL) parents of known ararcrcr genotype were set up to ascertain linkage between the tumour virus a (tva) and tumour virus c (tvc) loci. The results confirmed that in this RIR strain, the two loci, tva and tvc, control the cellular response to viruses of subgroups A and C, respectively, as reported in other breeds of fowl (WL and New Hampshire). As in WL fowl, the two loci are linked. The linkage value of 0-22 in the male sex agreed well with that reported in the WL male sex, indicating that the two loci are located in the same sites in homologous chromosomes in the two breeds. However, in the RIR strain, no sex difference in crossing over between the two linked loci was found, contrary to that reported in WL fowl where the absence of crossing over between the two loci was observed in the heterogametic female sex.", "contents": "Genetic control of resistance to subgroup A and subgroup C tumour viruses in Rhode Island Red fowl: evidence for linkage between the tumour virus a (tva) and tumour virus c (tvc) loci. A study, using the Rhode Island Red (RIR) strain of fowl maintained at Houghton Poultry Research Station, was made to investigate the genetic control of cellular response to infection with viruses of subgroups A and C. Family matings within the RIR strain and test-crosses between the RIR parents and White Leghorn (WL) parents of known ararcrcr genotype were set up to ascertain linkage between the tumour virus a (tva) and tumour virus c (tvc) loci. The results confirmed that in this RIR strain, the two loci, tva and tvc, control the cellular response to viruses of subgroups A and C, respectively, as reported in other breeds of fowl (WL and New Hampshire). As in WL fowl, the two loci are linked. The linkage value of 0-22 in the male sex agreed well with that reported in the WL male sex, indicating that the two loci are located in the same sites in homologous chromosomes in the two breeds. However, in the RIR strain, no sex difference in crossing over between the two linked loci was found, contrary to that reported in WL fowl where the absence of crossing over between the two loci was observed in the heterogametic female sex."}
{"id": "PMID:192841", "title": "Immunogenic and cell attachment sites of FMDV: further evidence for their location in a single capsid polypeptide.", "content": "Chymotrypsin cleaves only one of the four major polypeptides of foot-and-mouth disease virus (FMDV serotype O) in situ. This polypeptide (VP1, mol. wt. 29 X 10(3) was first cleaved into fragments of mol. wt. 20 and 9 X 10(3) and further cleavage could be prevented by the addition of a large excess of bovine serum albumin. The infectivity of the virus particles at this stage was the same as that of the intact virus although the rate of attachment to BHK 21 cells was slower and the immunogenic activity was reduced. If hydrolysis was allowed to continue, VP1 was cleaved into fragments with mol. wt. 18 and less than 9 X 10(3), similar to those obtained with trypsin and the virus particles then had a greatly  reduced infectivity and a lower immunogenicity. Treatment of strains from five other serotypes of the virus with the two enzymes cleaved only VP1 in each instance and there was a corresponding loss of infectivity. The results are discussed in relation to the location and biological activity of the virus polypeptides.", "contents": "Immunogenic and cell attachment sites of FMDV: further evidence for their location in a single capsid polypeptide. Chymotrypsin cleaves only one of the four major polypeptides of foot-and-mouth disease virus (FMDV serotype O) in situ. This polypeptide (VP1, mol. wt. 29 X 10(3) was first cleaved into fragments of mol. wt. 20 and 9 X 10(3) and further cleavage could be prevented by the addition of a large excess of bovine serum albumin. The infectivity of the virus particles at this stage was the same as that of the intact virus although the rate of attachment to BHK 21 cells was slower and the immunogenic activity was reduced. If hydrolysis was allowed to continue, VP1 was cleaved into fragments with mol. wt. 18 and less than 9 X 10(3), similar to those obtained with trypsin and the virus particles then had a greatly  reduced infectivity and a lower immunogenicity. Treatment of strains from five other serotypes of the virus with the two enzymes cleaved only VP1 in each instance and there was a corresponding loss of infectivity. The results are discussed in relation to the location and biological activity of the virus polypeptides."}
{"id": "PMID:192842", "title": "Thymidine transport in herpesvirus hominis type 1 and 2 infected BHK 21 cells.", "content": "Increase of dThd-uptake 4 to 12 h after infection of BHK or primary rabbit kidney cells with Herpesvirus hominis of type 1 or 2 can be considered as an early function of the virus genome, because the presence of Cyd-Ara does not prevent the increase of uptake. However, increase of uptake can be prevented by addition of actinomycin D and cycloheximide early in the synthetic cycle. Two modes of uptake have been differentiated by kinetic analysis: at low substrate concentration dThd is taken up by 'facilitated transport', whereas at high substrate concentration (above 2-5 micronM) simple diffusion takes place. The Km of transport of normal BHK or primary rabbit kidney cells (1-4 or 0-5 micronM respectively) is not changed after infection. Only the Vmax increases from 8 to 26-6 pmol in BHK cells or from 2-9 to 9-0 pmol in primary rabbit kidney cells. This indicates that 'carrier sites' with identical affinity for dThd-transport are responsible for the increase of transport after infection. This increase of transport is correlated with the induction of a virus coded thymidine kinase (TK) and not with different types of c.p.e. or cellular damage. Transport of BdUrd increases in a similar manner to that of dThd after infection; transport of dCyd or dUrd increases only slightly, whereas the mechanism of dAdo or Urd uptake by infected cells is quite different.", "contents": "Thymidine transport in herpesvirus hominis type 1 and 2 infected BHK 21 cells. Increase of dThd-uptake 4 to 12 h after infection of BHK or primary rabbit kidney cells with Herpesvirus hominis of type 1 or 2 can be considered as an early function of the virus genome, because the presence of Cyd-Ara does not prevent the increase of uptake. However, increase of uptake can be prevented by addition of actinomycin D and cycloheximide early in the synthetic cycle. Two modes of uptake have been differentiated by kinetic analysis: at low substrate concentration dThd is taken up by 'facilitated transport', whereas at high substrate concentration (above 2-5 micronM) simple diffusion takes place. The Km of transport of normal BHK or primary rabbit kidney cells (1-4 or 0-5 micronM respectively) is not changed after infection. Only the Vmax increases from 8 to 26-6 pmol in BHK cells or from 2-9 to 9-0 pmol in primary rabbit kidney cells. This indicates that 'carrier sites' with identical affinity for dThd-transport are responsible for the increase of transport after infection. This increase of transport is correlated with the induction of a virus coded thymidine kinase (TK) and not with different types of c.p.e. or cellular damage. Transport of BdUrd increases in a similar manner to that of dThd after infection; transport of dCyd or dUrd increases only slightly, whereas the mechanism of dAdo or Urd uptake by infected cells is quite different."}
{"id": "PMID:192843", "title": "Radioactive labelling of viruses: an iodination technique preserving biological properties.", "content": "An iodination procedure suitable for the radioactive labelling of viruses to be used in biological experiments is described. It is characterized by the addition of carrier protein to small amounts of virus before iodination with chloramine T, the use of low concentrations of chemicals, and a rapid purification of the labelled virus to minimize radiation inactivation. Using this procedure, polyoma virus was labelled to a specific activity 100 times greater than that which can be obtained with tritiated amino acids, while its sedimentation coefficient, buoyant density, decapsidation and hamagglutinating activity remained unaffected. Reduction in infectivity, possibly due to radiation inactivation, was slight. Similar results were obtained with adenovirus.", "contents": "Radioactive labelling of viruses: an iodination technique preserving biological properties. An iodination procedure suitable for the radioactive labelling of viruses to be used in biological experiments is described. It is characterized by the addition of carrier protein to small amounts of virus before iodination with chloramine T, the use of low concentrations of chemicals, and a rapid purification of the labelled virus to minimize radiation inactivation. Using this procedure, polyoma virus was labelled to a specific activity 100 times greater than that which can be obtained with tritiated amino acids, while its sedimentation coefficient, buoyant density, decapsidation and hamagglutinating activity remained unaffected. Reduction in infectivity, possibly due to radiation inactivation, was slight. Similar results were obtained with adenovirus."}
{"id": "PMID:192844", "title": "Role of sialic acid in infection with vesicular stomatitis virus.", "content": "The role of sialic acid in the infection of tissue culture cells and mice with vesicular stomatitis virus has been studied. No loss of infectivity of the Indiana serotype of the virus was detected by incubating with neuraminidase although the virus particles had lost sialic acid as judged by their ability to inhibit the agglutination of red blood cells by influenza virus. The results did not depend on the type of cell used for growth and assay of the virus since essentially similar findings were made in BHK cells, L cells or mice. Similar results were obtained with Brazil virus, a subtype of the Indiana serotype and with the New Jersey serotype. We consider that the sialic acid of the virus which is removed by neuraminidase does not play a major role in the infectivity of the virus.", "contents": "Role of sialic acid in infection with vesicular stomatitis virus. The role of sialic acid in the infection of tissue culture cells and mice with vesicular stomatitis virus has been studied. No loss of infectivity of the Indiana serotype of the virus was detected by incubating with neuraminidase although the virus particles had lost sialic acid as judged by their ability to inhibit the agglutination of red blood cells by influenza virus. The results did not depend on the type of cell used for growth and assay of the virus since essentially similar findings were made in BHK cells, L cells or mice. Similar results were obtained with Brazil virus, a subtype of the Indiana serotype and with the New Jersey serotype. We consider that the sialic acid of the virus which is removed by neuraminidase does not play a major role in the infectivity of the virus."}
{"id": "PMID:192845", "title": "Heterotypic exclusion between vesicular stomatitis viruses of the New Jersey and Indiana serotypes.", "content": "Co-infection of cells with vesicular stomatitis viruses of the Indiana and New Jersey serotypes results in interference. Using specifically-labelled immunofluorescent antibodies, it was demonstrated that within any one co-infected cell, one virus serotype replicated to the relative exclusion of the other serotype. This result was further substantiated by an examination of the virus serotypes released by infectious centres co-infected with both viruses. Dominance of one serotype over the other was shown to be a function of the relative multiplicity of the two viruses. Superinfection by the second serotype at a higher multiplicity resulted in dominance by the second virus during the early period (up to 1-5 h) post-infection. After this time, the minority virus was able to overcome this dominance. Dominance of the majority virus was also abolished by u.v; inactivation. Cell protein synthesis appeared to be less affected in cells infected with both serotypes than when infection was with a single serotype.", "contents": "Heterotypic exclusion between vesicular stomatitis viruses of the New Jersey and Indiana serotypes. Co-infection of cells with vesicular stomatitis viruses of the Indiana and New Jersey serotypes results in interference. Using specifically-labelled immunofluorescent antibodies, it was demonstrated that within any one co-infected cell, one virus serotype replicated to the relative exclusion of the other serotype. This result was further substantiated by an examination of the virus serotypes released by infectious centres co-infected with both viruses. Dominance of one serotype over the other was shown to be a function of the relative multiplicity of the two viruses. Superinfection by the second serotype at a higher multiplicity resulted in dominance by the second virus during the early period (up to 1-5 h) post-infection. After this time, the minority virus was able to overcome this dominance. Dominance of the majority virus was also abolished by u.v; inactivation. Cell protein synthesis appeared to be less affected in cells infected with both serotypes than when infection was with a single serotype."}
{"id": "PMID:192846", "title": "Requirement of the bacteriopahge T7 0.7 gene for phage growth in the presence of the Col 1b factor.", "content": "A variety of colicinogenic factors were examined for their effect on the growth of phages related to T7. Col B1 and Col B4 inhibited the growth of every phage tested. Col B2, however, did not interfere with T3 and H. Col E2 interfered only with growth of T3, while Col Ib produced abortive infection with some T7 mutants. The abortive infection associated with Col Ib seems to be correlated with the absence of the virus phosphokinase; mixed infection with T7 wild type and a phosphokinase deficient mutant was productive but the phage yield was depressed. The abortively infected cells lysed.", "contents": "Requirement of the bacteriopahge T7 0.7 gene for phage growth in the presence of the Col 1b factor. A variety of colicinogenic factors were examined for their effect on the growth of phages related to T7. Col B1 and Col B4 inhibited the growth of every phage tested. Col B2, however, did not interfere with T3 and H. Col E2 interfered only with growth of T3, while Col Ib produced abortive infection with some T7 mutants. The abortive infection associated with Col Ib seems to be correlated with the absence of the virus phosphokinase; mixed infection with T7 wild type and a phosphokinase deficient mutant was productive but the phage yield was depressed. The abortively infected cells lysed."}
{"id": "PMID:192851", "title": "The adrenal medulla may mediate the increase in pineal melatonin synthesis induced by stress, but not that caused by exposure to darkness.", "content": "As previously shown (Lynch et al.: Proc. Nat. Acad. Sci. [U.S.A.] 70, 1704-1707 [1973]), the activity of the enzyme serotonin-N-acetyltransferase (NAT) in the rat pineal increases when the animal is placed in darkness or is subjected to the stress of physical immobilization; partial sympathetic denervation (i.e., pretreatment of the animal with intravenous 6-hydroxydopamine [6-OHDA]) does not block either response. The present studies explored the roles of the pineal sympathetic nerves and the adrenal medullas in mediating these responses. The stress-induced increase in pineal NAT activity was blocked by bilateral adrenalectomy, but not by bilateral superior cervical ganglionectomy or by treatment with 6-OHDA (both of which potentiate the NAT response in normal rats and restore it in adrenalectomized ones). The increase in pineal melatonin content caused by immobilization was also blocked by adrenalectomy, but potentiated by pineal sympathetic denervation. In contrast, bilateral adrenalectomy did not affect the darkness-induced rise in pineal NAT activity, although pineal sympathetic denervation (by bilateral superior cervical ganglionectomy) did block this response. 6-OHDA pretreatment neither blocked the response to darkness nor restored it in ganglionectomized animals; thus, this treatment apparently fails to produce a complete pineal denervation. The pineal response to stress has previously been shown to be blocked by beta-adrenergic blocking agents. The present studies demonstrate that alpha-adrenergic blockade (with phenoxybenzamine) potentiates this response in intact animals and restores it in adrenalectomized rats (possibly by acting presynaptically on receptors on pineal sympathetic terminals and thereby augmenting norepinephrine release). These observations show that the rat pineal organ normally receives information from two \"channels\", i.e., trans-synaptically (from pineal sympathetic nerves) and via the circulation (from the adrenal medullas and, perhaps, from distant sympathetic nerves).", "contents": "The adrenal medulla may mediate the increase in pineal melatonin synthesis induced by stress, but not that caused by exposure to darkness. As previously shown (Lynch et al.: Proc. Nat. Acad. Sci. [U.S.A.] 70, 1704-1707 [1973]), the activity of the enzyme serotonin-N-acetyltransferase (NAT) in the rat pineal increases when the animal is placed in darkness or is subjected to the stress of physical immobilization; partial sympathetic denervation (i.e., pretreatment of the animal with intravenous 6-hydroxydopamine [6-OHDA]) does not block either response. The present studies explored the roles of the pineal sympathetic nerves and the adrenal medullas in mediating these responses. The stress-induced increase in pineal NAT activity was blocked by bilateral adrenalectomy, but not by bilateral superior cervical ganglionectomy or by treatment with 6-OHDA (both of which potentiate the NAT response in normal rats and restore it in adrenalectomized ones). The increase in pineal melatonin content caused by immobilization was also blocked by adrenalectomy, but potentiated by pineal sympathetic denervation. In contrast, bilateral adrenalectomy did not affect the darkness-induced rise in pineal NAT activity, although pineal sympathetic denervation (by bilateral superior cervical ganglionectomy) did block this response. 6-OHDA pretreatment neither blocked the response to darkness nor restored it in ganglionectomized animals; thus, this treatment apparently fails to produce a complete pineal denervation. The pineal response to stress has previously been shown to be blocked by beta-adrenergic blocking agents. The present studies demonstrate that alpha-adrenergic blockade (with phenoxybenzamine) potentiates this response in intact animals and restores it in adrenalectomized rats (possibly by acting presynaptically on receptors on pineal sympathetic terminals and thereby augmenting norepinephrine release). These observations show that the rat pineal organ normally receives information from two \"channels\", i.e., trans-synaptically (from pineal sympathetic nerves) and via the circulation (from the adrenal medullas and, perhaps, from distant sympathetic nerves)."}
{"id": "PMID:192854", "title": "Comparative effects of herpes simplex virus types 1 and 2 in organotypic cultures of mouse dorsal root ganglion.", "content": "Mature organized cultures of mouse dorsal root ganglion (MDRG) were infected with herpes simplex virus, type 1 (HSV 1) and type 2 (HSV 2). Onset of infectious virus production occurred faster and reached higher levels in HSV 2-infected cultures. Neurons, supporting cells and myelin were affected in both types of infection, but morphological changes occurred significantly earlier and more dramatically with the type 2 infection. The pattern of myelin changes was distinctly different in the two types of infection. Within 20 hours post infection nerve cells infected with HSV 2 developed several types of intranuclear inclusions consisting of membranes and filaments; no such neuronal inclusions were seen with HSV 1 infection. HSV 2 infection showed frequent, large, membranous inclusions in supporting cell nuclei whereas, only rare, small inclusions of this type were seen in supporting cells infected with HSV 1. The observations demonstrate that the two virus types produced different virus replication patterns and different morphologic changes in long term cultures of MDRG. There appears to be a differential response of neurons and non-neuronal elements to the virus in this tissue substrate. Viral latency was not induced in this system by direct inoculation of the virus under the conditions described.", "contents": "Comparative effects of herpes simplex virus types 1 and 2 in organotypic cultures of mouse dorsal root ganglion. Mature organized cultures of mouse dorsal root ganglion (MDRG) were infected with herpes simplex virus, type 1 (HSV 1) and type 2 (HSV 2). Onset of infectious virus production occurred faster and reached higher levels in HSV 2-infected cultures. Neurons, supporting cells and myelin were affected in both types of infection, but morphological changes occurred significantly earlier and more dramatically with the type 2 infection. The pattern of myelin changes was distinctly different in the two types of infection. Within 20 hours post infection nerve cells infected with HSV 2 developed several types of intranuclear inclusions consisting of membranes and filaments; no such neuronal inclusions were seen with HSV 1 infection. HSV 2 infection showed frequent, large, membranous inclusions in supporting cell nuclei whereas, only rare, small inclusions of this type were seen in supporting cells infected with HSV 1. The observations demonstrate that the two virus types produced different virus replication patterns and different morphologic changes in long term cultures of MDRG. There appears to be a differential response of neurons and non-neuronal elements to the virus in this tissue substrate. Viral latency was not induced in this system by direct inoculation of the virus under the conditions described."}
{"id": "PMID:192855", "title": "Computerized tomography as a possible aid to histological grading of supratentorial gliomas.", "content": "Computerized tomography (CT) is known to be very helpful in demostrating the presence and extent of supratentorial gliomas, practically in combination with intravenous injection of contrast material. Certain specific density patterns were found to exist and enabled us to differentiate with confidence the low-grade gliomas from the glioblastomas. Overlapping did occur, however, as was to be expected, since histological proof was sometimes obtained by the needle biopsy with its inherent doubt as to true tumor representation. Future CT techniques such as sequential scanning after intravenous injection of contrast material may further increase the usefulness of CT scans in the diagnosis and therapeutic approach to the patient with a suspected glioma.", "contents": "Computerized tomography as a possible aid to histological grading of supratentorial gliomas. Computerized tomography (CT) is known to be very helpful in demostrating the presence and extent of supratentorial gliomas, practically in combination with intravenous injection of contrast material. Certain specific density patterns were found to exist and enabled us to differentiate with confidence the low-grade gliomas from the glioblastomas. Overlapping did occur, however, as was to be expected, since histological proof was sometimes obtained by the needle biopsy with its inherent doubt as to true tumor representation. Future CT techniques such as sequential scanning after intravenous injection of contrast material may further increase the usefulness of CT scans in the diagnosis and therapeutic approach to the patient with a suspected glioma."}
{"id": "PMID:192856", "title": "Intracranial biopsy assisted by computerized tomography.", "content": "A technique is described for biopsying intracranial tumors and aspirating cysts or abscesses using flexible non-metallic needle guides and computerized tomography a guidance system. Three cases are described in which this technique was used.", "contents": "Intracranial biopsy assisted by computerized tomography. A technique is described for biopsying intracranial tumors and aspirating cysts or abscesses using flexible non-metallic needle guides and computerized tomography a guidance system. Three cases are described in which this technique was used."}
{"id": "PMID:192857", "title": "The scintigraphic investigation of sacroiliac disease.", "content": "Bone scintigraphs obtained with both Technetium-99m polyphosphate and Technetium-99m pyrophosphate have been abnormal at the sacroiliac joints of 44 patients with definite ankylosing spondylitis (AS). Because of the normal registration of the sacroiliac joints on bone scintigraphy, it has been necessary to develop a profile-scan technique to quantify the abnormality that proves to be significantly different from the normal finding. In 17 patients with a strong clinical suspicion of AS but normal radiographs, the sacroiliac joints have frequently been abnormal. This finding is meaningful because there is a common occurence in this group of the histocompatibility antigen HL A-B27, known to be a marker of AS. We also note the frequency of abnormal sacroiliac scinitigrams in 26 patients with rheumatoid arthritis and in a group of other diseases-Crohn's disease, uveitis, psoriasis, ulcerative colitis, and Reiter's disease-all of which share some of the manifestations of AS.", "contents": "The scintigraphic investigation of sacroiliac disease. Bone scintigraphs obtained with both Technetium-99m polyphosphate and Technetium-99m pyrophosphate have been abnormal at the sacroiliac joints of 44 patients with definite ankylosing spondylitis (AS). Because of the normal registration of the sacroiliac joints on bone scintigraphy, it has been necessary to develop a profile-scan technique to quantify the abnormality that proves to be significantly different from the normal finding. In 17 patients with a strong clinical suspicion of AS but normal radiographs, the sacroiliac joints have frequently been abnormal. This finding is meaningful because there is a common occurence in this group of the histocompatibility antigen HL A-B27, known to be a marker of AS. We also note the frequency of abnormal sacroiliac scinitigrams in 26 patients with rheumatoid arthritis and in a group of other diseases-Crohn's disease, uveitis, psoriasis, ulcerative colitis, and Reiter's disease-all of which share some of the manifestations of AS."}
{"id": "PMID:192859", "title": "Evaluation of formamidine sulfinic acid and other reducing agents for use in the preparation of Tc-99m labeled radiopharmaceuticals.", "content": "Various reducing agents have been evaluated for their potential usefulness in the preparation of 99mTc labeled radiopharmaceuticals for use in nuclear medicine. Adequate labeling of various radiopharmaceuticals was accomplished using formamidine sulfinic acid. Nitrogen-purging of solutions is not required, which is an advantage for in-house preparation. Tagging requires heating, however, so heat-labile material cannot be used. Various compounds that could not be labeled when stannous chloride was used, could be tagged with 99mTc when formanidine sulfinic acid was used as the reducing agent.", "contents": "Evaluation of formamidine sulfinic acid and other reducing agents for use in the preparation of Tc-99m labeled radiopharmaceuticals. Various reducing agents have been evaluated for their potential usefulness in the preparation of 99mTc labeled radiopharmaceuticals for use in nuclear medicine. Adequate labeling of various radiopharmaceuticals was accomplished using formamidine sulfinic acid. Nitrogen-purging of solutions is not required, which is an advantage for in-house preparation. Tagging requires heating, however, so heat-labile material cannot be used. Various compounds that could not be labeled when stannous chloride was used, could be tagged with 99mTc when formanidine sulfinic acid was used as the reducing agent."}
{"id": "PMID:192860", "title": "Effect of adaptation to meal-feeding on insulin, glucagon and the cyclic nucleotide-protein kinase system in rats.", "content": "Diurnal changes in insulin, glucagon and the cyclic nucleotide-protein kinase system were examined in rats trained to eat a 2-hour daily meal and in control rats fed ad libitum. Sharp increases in both insulin and glucagon were observed in response to feeding in trained rats. However, throughout most of the rest of the day, the plasma concentrations of both hormones were lower in meal-fed than in control rats. In adipose tissue, diurnal changes in cyclic AMP concentration were inversely correlated with changes in plasma insulin concentration. In general, cyclic AMP concentrations were depressed and cyclic GMP elevated in adipose tissue of meal-fed rats compared with those fed ad libitum. Diurnal changes in cyclic GMP concentration tended to parallel those of cyclic AMP. Cyclic AMP-activated protein kinase was elevated in adipose tissue of meal-fed rats. However, with the exception of fasting rats, the percentage of the enzyme in the active form was decreased. In liver, there was no clear relation significant differenced were observed with the protein kinase. It can be concluded that the magnitude of the adaptive response of the cyclic nucleotide-protein kinase system to meal-feeding in rats is greater in adipose tissue than in liver.", "contents": "Effect of adaptation to meal-feeding on insulin, glucagon and the cyclic nucleotide-protein kinase system in rats. Diurnal changes in insulin, glucagon and the cyclic nucleotide-protein kinase system were examined in rats trained to eat a 2-hour daily meal and in control rats fed ad libitum. Sharp increases in both insulin and glucagon were observed in response to feeding in trained rats. However, throughout most of the rest of the day, the plasma concentrations of both hormones were lower in meal-fed than in control rats. In adipose tissue, diurnal changes in cyclic AMP concentration were inversely correlated with changes in plasma insulin concentration. In general, cyclic AMP concentrations were depressed and cyclic GMP elevated in adipose tissue of meal-fed rats compared with those fed ad libitum. Diurnal changes in cyclic GMP concentration tended to parallel those of cyclic AMP. Cyclic AMP-activated protein kinase was elevated in adipose tissue of meal-fed rats. However, with the exception of fasting rats, the percentage of the enzyme in the active form was decreased. In liver, there was no clear relation significant differenced were observed with the protein kinase. It can be concluded that the magnitude of the adaptive response of the cyclic nucleotide-protein kinase system to meal-feeding in rats is greater in adipose tissue than in liver."}
{"id": "PMID:192861", "title": "Effect of zinc deficiency on the ultrastructure of the pancreatic acinar cell and intestinal epithelium in the rat.", "content": "Ultrastructural changes in the pancreatic acinar cell and intestinal epithelium were studied in rats fed a zinc-deficient diet as compared with those of pair-fed and ad libitum fed zinc-supplemented controls. The pancreatic acinar cells of zinc-deficient rats showed marked cellular alterations: a reduction in zymogen granules, rupture of zymogen granules, basal accumulation lipid droplets, prominent lysosome-like bodies, focal degradation of the cytoplasm, and intracistenal granules within the dilated cisternae of the endoplasmic reticulum. The Golgi complex appeared inactive, and nuclear pyknosis was noted. Defects in the endoplasmic reticulum and ribosomes were  shown by their presence in the foci of cytoplasmic degradation, which were subsequently subject to lysosomal digestion and degeneration. The microvilli of the intestinal epithelium in the zinc deficient rats were well organized and normal in size, demonstrating a typical geometric array when cross-sectioned. The intercellular boundaries, the junctional complexes, and the terminal web were well developed and appeared intact. However, the cell cytoplasm showed prominent cellular changes: an abundance of lysosome-like bodies, membrane-bound autopraphic vacuoles, sparse endoplasmic reticulum, a quiescent-appearing Golgi complex with tightly packed lamellae containing few vacuoles, pyknotic nuclei, and a dilated nuclear periphery.", "contents": "Effect of zinc deficiency on the ultrastructure of the pancreatic acinar cell and intestinal epithelium in the rat. Ultrastructural changes in the pancreatic acinar cell and intestinal epithelium were studied in rats fed a zinc-deficient diet as compared with those of pair-fed and ad libitum fed zinc-supplemented controls. The pancreatic acinar cells of zinc-deficient rats showed marked cellular alterations: a reduction in zymogen granules, rupture of zymogen granules, basal accumulation lipid droplets, prominent lysosome-like bodies, focal degradation of the cytoplasm, and intracistenal granules within the dilated cisternae of the endoplasmic reticulum. The Golgi complex appeared inactive, and nuclear pyknosis was noted. Defects in the endoplasmic reticulum and ribosomes were  shown by their presence in the foci of cytoplasmic degradation, which were subsequently subject to lysosomal digestion and degeneration. The microvilli of the intestinal epithelium in the zinc deficient rats were well organized and normal in size, demonstrating a typical geometric array when cross-sectioned. The intercellular boundaries, the junctional complexes, and the terminal web were well developed and appeared intact. However, the cell cytoplasm showed prominent cellular changes: an abundance of lysosome-like bodies, membrane-bound autopraphic vacuoles, sparse endoplasmic reticulum, a quiescent-appearing Golgi complex with tightly packed lamellae containing few vacuoles, pyknotic nuclei, and a dilated nuclear periphery."}
{"id": "PMID:192862", "title": "Effect of zinc deficiency on intestinal transport triglyceride in the rat.", "content": "Ultrastructural and biochemical changes in the intestinal epithelium during the process of active triglyceride absorption were studied in rats fed a zinc-deficient diet as compared with those of pair-fed and ad libitum-fed zinc-supplemented controls. The rate of triglyceride absorption markedly decreased in zinc-deficient rats. Despite a significant reduction in pancreatic lipase activity, the digestion of triglycerides proceeded normally in the zinc deficient rats, as evidenced by  no apparent signs of diarrhea (or steatorrhea) and by the appearance of the hydrolytic products such as free-fatty acids and monoglycerides in the intestinal mucosa. The mucosa uptake of digested lipids and resynthesis of triglycerides in the mucosa from deficient rats were normal. Ultrastructural and chromatographic analysis of the mucosal lipids indicated a massive accumulation of lipid droplets, predominantly in the form of triglycerides. The primary defect in lipid absorptive processes in zinc-deficient rats occurred in the formation of chylomicrons. The lipid droplets in the mucosa of  deficient rats were physically unstable. This instability was shown by coalescence of droplets which did not appear to be membrane-bound. Coalescing lipid droplets ranged from 2.0 to 4.0 micron in diameter. The absorptive cells were not able to discharge lipid droplets of this size into the intercellular spaces and hence into the lamina propria, resulting in the accumulation of the large droplets within the mucosa. This exit block to the movement of lipid droplets out of the mucosal cell appeared to be due to the failure, in zinc-deficiency, of the mucosal synthesis of proteins required for the formation of chylomicrons. Ultrastructural observations demonstrated changes in the subcellular organelles related to protein synthesis, including a marked reduction in granular endoplasmic reticulum and a quiescent appearance of the Golgi-complex.", "contents": "Effect of zinc deficiency on intestinal transport triglyceride in the rat. Ultrastructural and biochemical changes in the intestinal epithelium during the process of active triglyceride absorption were studied in rats fed a zinc-deficient diet as compared with those of pair-fed and ad libitum-fed zinc-supplemented controls. The rate of triglyceride absorption markedly decreased in zinc-deficient rats. Despite a significant reduction in pancreatic lipase activity, the digestion of triglycerides proceeded normally in the zinc deficient rats, as evidenced by  no apparent signs of diarrhea (or steatorrhea) and by the appearance of the hydrolytic products such as free-fatty acids and monoglycerides in the intestinal mucosa. The mucosa uptake of digested lipids and resynthesis of triglycerides in the mucosa from deficient rats were normal. Ultrastructural and chromatographic analysis of the mucosal lipids indicated a massive accumulation of lipid droplets, predominantly in the form of triglycerides. The primary defect in lipid absorptive processes in zinc-deficient rats occurred in the formation of chylomicrons. The lipid droplets in the mucosa of  deficient rats were physically unstable. This instability was shown by coalescence of droplets which did not appear to be membrane-bound. Coalescing lipid droplets ranged from 2.0 to 4.0 micron in diameter. The absorptive cells were not able to discharge lipid droplets of this size into the intercellular spaces and hence into the lamina propria, resulting in the accumulation of the large droplets within the mucosa. This exit block to the movement of lipid droplets out of the mucosal cell appeared to be due to the failure, in zinc-deficiency, of the mucosal synthesis of proteins required for the formation of chylomicrons. Ultrastructural observations demonstrated changes in the subcellular organelles related to protein synthesis, including a marked reduction in granular endoplasmic reticulum and a quiescent appearance of the Golgi-complex."}
{"id": "PMID:192863", "title": "Role of dietary calcium and calcium binding protein in cadmium toxicity in rats.", "content": "Growing male rats were fed a purified diet containing 0.6% Ca (two groups) or 0.1% Ca (two groups) for 8 weeks. One 0.6% Ca group and one 0.1% Ca group received 25 ppm Cd (as CdC12) in the drinking water. Diets were fed on an equalized basis with the 0.1% Ca + Cd group determining the amount of diet fed to the other groups. Water was provided ad libitum. Terminal body weights were not different among the four groups. Packed cell volumes were depressed in the Cd-exposed groups, especially the 0.1% Ca + Cd group. The highest concentrations of Cd were found in the lungs, liver, and kidneys of the 0.1% Ca + Cd group. More Cd was bound to low molecular weight proteins of the intestinal mucosa from the 0.1% Ca + Cd group than the 0.6% Ca + Cd group. Rats fed the 0.1% Ca diet appeared to have a greater capacity to absorb either Ca or Cd than rats fed the 0.6% Ca diet, as shown by an enhanced binding of 45Ca and  115mCd to intestinal calcium-binding protein (CaBP) in the rats fed the low calcium diet. A portion of the mucosal Cd was accounted for as Cd bound to metallothionein. It was concluded, based upon these experiments, that cadmium retention and signs of toxicity are enhanced by feeding low Ca diet and that the increased CaBP activity due to Ca restrictions is responsible for the increased Cd uptake observed.", "contents": "Role of dietary calcium and calcium binding protein in cadmium toxicity in rats. Growing male rats were fed a purified diet containing 0.6% Ca (two groups) or 0.1% Ca (two groups) for 8 weeks. One 0.6% Ca group and one 0.1% Ca group received 25 ppm Cd (as CdC12) in the drinking water. Diets were fed on an equalized basis with the 0.1% Ca + Cd group determining the amount of diet fed to the other groups. Water was provided ad libitum. Terminal body weights were not different among the four groups. Packed cell volumes were depressed in the Cd-exposed groups, especially the 0.1% Ca + Cd group. The highest concentrations of Cd were found in the lungs, liver, and kidneys of the 0.1% Ca + Cd group. More Cd was bound to low molecular weight proteins of the intestinal mucosa from the 0.1% Ca + Cd group than the 0.6% Ca + Cd group. Rats fed the 0.1% Ca diet appeared to have a greater capacity to absorb either Ca or Cd than rats fed the 0.6% Ca diet, as shown by an enhanced binding of 45Ca and  115mCd to intestinal calcium-binding protein (CaBP) in the rats fed the low calcium diet. A portion of the mucosal Cd was accounted for as Cd bound to metallothionein. It was concluded, based upon these experiments, that cadmium retention and signs of toxicity are enhanced by feeding low Ca diet and that the increased CaBP activity due to Ca restrictions is responsible for the increased Cd uptake observed."}
{"id": "PMID:192865", "title": "Problem of sex ratio in cases of type I syndactyly.", "content": "Fifty pedigrees of type I syndactyly were analysed for sex ratio and segreation pattern. Thirty-four of the pedigrees were from the published reports; 16 were collected in the State of Utah. Pedigrees with affected individuals showing webbing between the second and third toes are characterized by a sex ratio of affected individuals favouring males and a highly significant excess of affected sons of heterozygous fathers. A similar distorted segregation pattern is present in those pedigrees when the webbing involves the second and third toes and/or the third and fourth fingers, but not in those pedigrees when the webbing involves other digits. The reason for the distorted segregation pattern is unknown. Hypothesis include abnormal chromosome segregation and gametic selection.", "contents": "Problem of sex ratio in cases of type I syndactyly. Fifty pedigrees of type I syndactyly were analysed for sex ratio and segreation pattern. Thirty-four of the pedigrees were from the published reports; 16 were collected in the State of Utah. Pedigrees with affected individuals showing webbing between the second and third toes are characterized by a sex ratio of affected individuals favouring males and a highly significant excess of affected sons of heterozygous fathers. A similar distorted segregation pattern is present in those pedigrees when the webbing involves the second and third toes and/or the third and fourth fingers, but not in those pedigrees when the webbing involves other digits. The reason for the distorted segregation pattern is unknown. Hypothesis include abnormal chromosome segregation and gametic selection."}
{"id": "PMID:192866", "title": "A partial long arm deletion of chromosome 7:46,XY,del(7)(q32).", "content": "We have identified a partial deletion of the long arm of chromosome 7 in a newborn baby boy. His major anomalies were microcephaly, synbrachydactyly, diastisis recti, hypospadias, short neck, and widely spaced nipples.", "contents": "A partial long arm deletion of chromosome 7:46,XY,del(7)(q32). We have identified a partial deletion of the long arm of chromosome 7 in a newborn baby boy. His major anomalies were microcephaly, synbrachydactyly, diastisis recti, hypospadias, short neck, and widely spaced nipples."}
{"id": "PMID:192867", "title": "Reovirus-like agent as a cause of nosocomial diarrhea in infants.", "content": "Surveillance for nosocomial diarrhea due to a reovirus-like agent was maintained on the pediatric wards of a large metropolitan hospital in January and February, 1976, during a large community outbreak of that illness. During this period, 30 (27%) of 111 children under surveillance were admitted for dehydration secondary to diarrhea; 21 (70%) of these 30 children had RLA in stool samples obtained at admission. Ten (17%) of the 60 children admitted without diarrhea, hence at risk of acquiring nosocomial RLA infection, contracted the illness. With human RLA as an antigen, no hospital personnel had serologic (complement fixation test) evidence of infection. Early attempts to control the diarrhea at home and in the outpatient department by the use of oral fluid rehydration, isolation of patients with severe symptoms requiring hospitalization, and strict attention by hospital personnel to hand washing between examination of patients may limit nosocomial spread of the disease.", "contents": "Reovirus-like agent as a cause of nosocomial diarrhea in infants. Surveillance for nosocomial diarrhea due to a reovirus-like agent was maintained on the pediatric wards of a large metropolitan hospital in January and February, 1976, during a large community outbreak of that illness. During this period, 30 (27%) of 111 children under surveillance were admitted for dehydration secondary to diarrhea; 21 (70%) of these 30 children had RLA in stool samples obtained at admission. Ten (17%) of the 60 children admitted without diarrhea, hence at risk of acquiring nosocomial RLA infection, contracted the illness. With human RLA as an antigen, no hospital personnel had serologic (complement fixation test) evidence of infection. Early attempts to control the diarrhea at home and in the outpatient department by the use of oral fluid rehydration, isolation of patients with severe symptoms requiring hospitalization, and strict attention by hospital personnel to hand washing between examination of patients may limit nosocomial spread of the disease."}
{"id": "PMID:192873", "title": "Endocrine function following the treatment of acute leukemia in childhood.", "content": "Pituitary function has been studied in 25 children after treatment of acute leukemia. Impaired growth hormone responses both to hypoglycemia and to Bovril were found in 11 subjects. Elevated basal thyroid-stimulating hormone levels were seen in five children, three of whom had an augmented TSH response to thyrotrophin-releasing hormone. Radiation-induced damage to the hypothalamic-pituitary region is thought to be the cause of these abnormalities in growth hormone and in secretion of TSH. The peak cortisol response to hypoglycaemia is significantly decreased in the group of subjects who received the higher dose of cranial radiation therapy, but no individual child is hypothyroid or shows impaired adrenal function, clinically or biochemically. Three prepubertal girls studied have biochemical evidence of ovarian failure following the use of combination chemotherapy.", "contents": "Endocrine function following the treatment of acute leukemia in childhood. Pituitary function has been studied in 25 children after treatment of acute leukemia. Impaired growth hormone responses both to hypoglycemia and to Bovril were found in 11 subjects. Elevated basal thyroid-stimulating hormone levels were seen in five children, three of whom had an augmented TSH response to thyrotrophin-releasing hormone. Radiation-induced damage to the hypothalamic-pituitary region is thought to be the cause of these abnormalities in growth hormone and in secretion of TSH. The peak cortisol response to hypoglycaemia is significantly decreased in the group of subjects who received the higher dose of cranial radiation therapy, but no individual child is hypothyroid or shows impaired adrenal function, clinically or biochemically. Three prepubertal girls studied have biochemical evidence of ovarian failure following the use of combination chemotherapy."}
{"id": "PMID:192874", "title": "The detection of the heterozygous carrier for congenital virilizing adrenal hyperplasia.", "content": "The response of plasma progesterone, 17 alpha-hydroxyprogesterone (17-OHP), and cortisol to intravenous ACTH was determined in 16 control subjects and seven sets of parents of children with congenital virilizing adrenal hyperplasia. The baseline and poststimulation concentrations of hormones (of each group) were similar except for those of 17-OHP in the parents which were significantly greater following administration of ACTH. When rates of increase were determined, those of progesterone and 17-OHP but not cortisol were significantly greater in the parents. The combined rate of increase of progesterone and 17-OHP was calculated; 10 of the 14 parents had a combined rate of increase greater than the mean plus two standard deviations of the control group. This test provides a simple method for the detection of some heterozygous carriers for CVAH.", "contents": "The detection of the heterozygous carrier for congenital virilizing adrenal hyperplasia. The response of plasma progesterone, 17 alpha-hydroxyprogesterone (17-OHP), and cortisol to intravenous ACTH was determined in 16 control subjects and seven sets of parents of children with congenital virilizing adrenal hyperplasia. The baseline and poststimulation concentrations of hormones (of each group) were similar except for those of 17-OHP in the parents which were significantly greater following administration of ACTH. When rates of increase were determined, those of progesterone and 17-OHP but not cortisol were significantly greater in the parents. The combined rate of increase of progesterone and 17-OHP was calculated; 10 of the 14 parents had a combined rate of increase greater than the mean plus two standard deviations of the control group. This test provides a simple method for the detection of some heterozygous carriers for CVAH."}
{"id": "PMID:192875", "title": "\"Flecked retina\" --an association with primary hyperoxaluria.", "content": "A child with hyperoxaluria, probable Type I, was noted to have a \"flecked retina\" on funduscopic examination at age 2 1/2 months; it persisted throughout his seven years of life. The relationship of the ocular findings to his metabolic disease is discussed.", "contents": "\"Flecked retina\" --an association with primary hyperoxaluria. A child with hyperoxaluria, probable Type I, was noted to have a \"flecked retina\" on funduscopic examination at age 2 1/2 months; it persisted throughout his seven years of life. The relationship of the ocular findings to his metabolic disease is discussed."}
{"id": "PMID:192878", "title": "GLC assay of conjugated estrogen formulations.", "content": "A procedure is described for the enzyme hydrolysis and GLC assay of conjugated estrogens in commercial formulations. Resolution of up to nine of the components is achieved on a methyl phenyl cyanopropyl silicone-coated column using a dual-derivatization and dual-injection technique. Replicate results from analyses of a commercial tablet formulation yielded coefficients of variation between 1.0 and 17.2%, depending mainly on the quantity present; a coefficient of variation of 0.4% was obtained for the assay for total conjugated estrogens. Similar results were obtained with other commercial formulations.", "contents": "GLC assay of conjugated estrogen formulations. A procedure is described for the enzyme hydrolysis and GLC assay of conjugated estrogens in commercial formulations. Resolution of up to nine of the components is achieved on a methyl phenyl cyanopropyl silicone-coated column using a dual-derivatization and dual-injection technique. Replicate results from analyses of a commercial tablet formulation yielded coefficients of variation between 1.0 and 17.2%, depending mainly on the quantity present; a coefficient of variation of 0.4% was obtained for the assay for total conjugated estrogens. Similar results were obtained with other commercial formulations."}
{"id": "PMID:192879", "title": "Cutaneous facilitation of transmission in reflex pathways from Ib afferents to motoneurones.", "content": "1. The effect of volleys in low threshold cutaneous afferents upon transmission of synaptic action from Ib afferents to motoneurones has been investigated with intracellular recording from alpha motoneurones to hind limb muscles. 2. There was facilitation from cutaneous afferents of transmission in excitatory and inhibitory reflex pathways from Ib afferents without any evidence for difference in effect on di- and trisynaptic pathways. It is postulated that volleys in cutaneous afferents evoke excitatory action in interneurones of these reflex pathways. 3. The time course of the facilitation suggest that cutaneous afferents have disynaptic excitatory connexions with the interneurones intercalated in the disynaptic Ib inhibitory pathways to motoneurones. 4. Some observations are reported suggesting that interneuronal transmission in Ib inhibitory pathways to motoneurones might be facilitated from Ia afferents. 5. The findings are discussed in relation to the presumed role of Ib reflex action in regulating muscle tension.", "contents": "Cutaneous facilitation of transmission in reflex pathways from Ib afferents to motoneurones. 1. The effect of volleys in low threshold cutaneous afferents upon transmission of synaptic action from Ib afferents to motoneurones has been investigated with intracellular recording from alpha motoneurones to hind limb muscles. 2. There was facilitation from cutaneous afferents of transmission in excitatory and inhibitory reflex pathways from Ib afferents without any evidence for difference in effect on di- and trisynaptic pathways. It is postulated that volleys in cutaneous afferents evoke excitatory action in interneurones of these reflex pathways. 3. The time course of the facilitation suggest that cutaneous afferents have disynaptic excitatory connexions with the interneurones intercalated in the disynaptic Ib inhibitory pathways to motoneurones. 4. Some observations are reported suggesting that interneuronal transmission in Ib inhibitory pathways to motoneurones might be facilitated from Ia afferents. 5. The findings are discussed in relation to the presumed role of Ib reflex action in regulating muscle tension."}
{"id": "PMID:192880", "title": "Effect of implantation of an extra nerve on the recovery of neuromuscular transmission from botulinum toxin.", "content": "1. The common peroneal nerve was implanted into soleus in the mouse and 2 weeks later a sublethal dose of botulinum toxin injected causing a block of neuromuscular transmission at the terminals of the soleus nerve. Most muscle fibres became innervated by the common peroneal nerve. 2. Recovery of neuromuscular transmission at the soleus nerve terminals was delayed in the common peroneal nerve implanted muscles. 3. Stimulation of the soleus nerve after botulinum-evoked subthreshold end-plate potentials (e.p.p.s) in virtually every fibre tested in unoperated muscles. In common peroneal nerve-implanted muscles stimulation of the soleus nerve failed to evoke e.p.p.s in about 40% of fibres tested and where e.p.p.s were recorded their amplitudes were generally smaller. 4. When the common peroneal nerve was cut 2 months after botulinum, neuromuscular transmission at soleus nerve terminals occurred after 4 weeks. When the common peroneal nerve was cut 6 months after botulinum, transmission was found at soleus nerve terminals within 1 week. 5. Recovery of transmission at soleus nerve terminals from the effects of botulinum toxin is delayed if the muscle fibres become innervated by the common peroneal nerve and a proportion of soleus nerve terminals cease to release acetylcholine (ACh) until after the peroneal nerve has been cut.", "contents": "Effect of implantation of an extra nerve on the recovery of neuromuscular transmission from botulinum toxin. 1. The common peroneal nerve was implanted into soleus in the mouse and 2 weeks later a sublethal dose of botulinum toxin injected causing a block of neuromuscular transmission at the terminals of the soleus nerve. Most muscle fibres became innervated by the common peroneal nerve. 2. Recovery of neuromuscular transmission at the soleus nerve terminals was delayed in the common peroneal nerve implanted muscles. 3. Stimulation of the soleus nerve after botulinum-evoked subthreshold end-plate potentials (e.p.p.s) in virtually every fibre tested in unoperated muscles. In common peroneal nerve-implanted muscles stimulation of the soleus nerve failed to evoke e.p.p.s in about 40% of fibres tested and where e.p.p.s were recorded their amplitudes were generally smaller. 4. When the common peroneal nerve was cut 2 months after botulinum, neuromuscular transmission at soleus nerve terminals occurred after 4 weeks. When the common peroneal nerve was cut 6 months after botulinum, transmission was found at soleus nerve terminals within 1 week. 5. Recovery of transmission at soleus nerve terminals from the effects of botulinum toxin is delayed if the muscle fibres become innervated by the common peroneal nerve and a proportion of soleus nerve terminals cease to release acetylcholine (ACh) until after the peroneal nerve has been cut."}
{"id": "PMID:192882", "title": "Effects of guanidine on transmitter release and neuronal excitability.", "content": "1. Guanidine hydrochloride (CH5N3-HCl) was applied to frog neuromuscular junctions blocked by reduced external Ca2+, or increased external Mg2+ concentration, or by both. Guanidine produced a dose-dependent increase in the average number of quanta released by presynaptic action potentials, the threshold dose being 0-1-0-2 mM. No post-synaptic effects were observed. 2. Guanidine also increased the excitability of the motor nerve fibres, as evidenced by multiple firing to single electrical stimuli and finally by spontaneous action potentials. These effects were studied in greater detail in giant axons (M\u00fcller axons) in the spinal cord of lamprey. Exposure to guanidine produced in these axons a progressive increase in excitability, manifested by repetitive firing to a single electrical stimulus, spontaneous membrane potential oscillations and spontaneous bursts of action potentials. Guanidine had no effect on the resting potential. 3. The effect of guanidine on the excitability of M\u00fcller axons was mimicked in every detail simply by reducing the divalent cation concentration of the bathing solution. 4. Guanidine also produced dose-dependent increases in the duration of action potentials in M\u00fcller axons. This effect always preceded in time the appearance of the excitability effects and was not mimicked by reducing the divalent cation concentration. It is suggested that the broadening of the action potential is separate from the excitability effects and may reflect a decrease of delayed rectification. 5. Guanidine (0-3 mM) increased the frequency of miniature end-plate potentials (min. e.p.p.) in solutions containing 2-11 mM-K+ in such a way as to shift the relationship between min. e.p.p. frequency and extracellular K+ toward lower values of K+. This effect was interpreted to mean that guanidine produced a depolarization of the nerve terminal which summed with the depolarization produced by a given concentration of K+. The calculated depolarization produced by 0-3 mM guanidine was 5-7 mV. 6. The effects of guanidine on evoked transmitter release, excitability, and min. e.p.p. frequency are consistent with a hypothesis which states that guanidine binds at or near fixed negative changes on the outside of nerve membrane and reduces the screening effect of divalent cations.", "contents": "Effects of guanidine on transmitter release and neuronal excitability. 1. Guanidine hydrochloride (CH5N3-HCl) was applied to frog neuromuscular junctions blocked by reduced external Ca2+, or increased external Mg2+ concentration, or by both. Guanidine produced a dose-dependent increase in the average number of quanta released by presynaptic action potentials, the threshold dose being 0-1-0-2 mM. No post-synaptic effects were observed. 2. Guanidine also increased the excitability of the motor nerve fibres, as evidenced by multiple firing to single electrical stimuli and finally by spontaneous action potentials. These effects were studied in greater detail in giant axons (M\u00fcller axons) in the spinal cord of lamprey. Exposure to guanidine produced in these axons a progressive increase in excitability, manifested by repetitive firing to a single electrical stimulus, spontaneous membrane potential oscillations and spontaneous bursts of action potentials. Guanidine had no effect on the resting potential. 3. The effect of guanidine on the excitability of M\u00fcller axons was mimicked in every detail simply by reducing the divalent cation concentration of the bathing solution. 4. Guanidine also produced dose-dependent increases in the duration of action potentials in M\u00fcller axons. This effect always preceded in time the appearance of the excitability effects and was not mimicked by reducing the divalent cation concentration. It is suggested that the broadening of the action potential is separate from the excitability effects and may reflect a decrease of delayed rectification. 5. Guanidine (0-3 mM) increased the frequency of miniature end-plate potentials (min. e.p.p.) in solutions containing 2-11 mM-K+ in such a way as to shift the relationship between min. e.p.p. frequency and extracellular K+ toward lower values of K+. This effect was interpreted to mean that guanidine produced a depolarization of the nerve terminal which summed with the depolarization produced by a given concentration of K+. The calculated depolarization produced by 0-3 mM guanidine was 5-7 mV. 6. The effects of guanidine on evoked transmitter release, excitability, and min. e.p.p. frequency are consistent with a hypothesis which states that guanidine binds at or near fixed negative changes on the outside of nerve membrane and reduces the screening effect of divalent cations."}
{"id": "PMID:192883", "title": "On the effect of calcium on the frequency of miniature end-plate potentials at the frog neuromuscular junction.", "content": "1. The effect of the extracellular Ca concentration on the frequency of miniature end-plate potentials (min. e.p.p.s) at the frog neuromuscular junction was studied. 2. In saline containing elevated K (5 or 11 mM), the frequency of min. e.p.p.s increased as Ca concentration was increased from 0-1 to 1-3 mM. However, with further increases of Ca concentration up to 10 mM, min. E.P.P. frequency declined. 3. In saline containing the normal concentration of K (2 mM), increasing Ca concentration from 0-1 to 10 mM produced a slight, monotonic increase in min. e.p.p. frequency. 4. The non-monotonic effect of Ca on min. e.p.p. frequency in preparations depolarized by elevated K is consistent with the existence of two opposing effects of Ca on transmitter release. Firstly, raising the external concentration of Ca increases the electrochemical potential for Ca entry, which tends to increase Ca influx and transmitter release. Secondly, increasing external Ca concentration increases electrostatic screening of fixed negative charges on the outer surface of the nerve terminal membrane. Such an increase in screening of charges near voltage-sensitive Ca gates would produce a hyperpolarization across the gates and they would tend to close, an effect which would tend to decrease Ca influx. The monotonic increase in min. e.p.p. frequency with increasing Ca concentration in 2 mM-K is consistent with the voltage insensitivity of the Ca gates at potentials close to the normal resting potential.", "contents": "On the effect of calcium on the frequency of miniature end-plate potentials at the frog neuromuscular junction. 1. The effect of the extracellular Ca concentration on the frequency of miniature end-plate potentials (min. e.p.p.s) at the frog neuromuscular junction was studied. 2. In saline containing elevated K (5 or 11 mM), the frequency of min. e.p.p.s increased as Ca concentration was increased from 0-1 to 1-3 mM. However, with further increases of Ca concentration up to 10 mM, min. E.P.P. frequency declined. 3. In saline containing the normal concentration of K (2 mM), increasing Ca concentration from 0-1 to 10 mM produced a slight, monotonic increase in min. e.p.p. frequency. 4. The non-monotonic effect of Ca on min. e.p.p. frequency in preparations depolarized by elevated K is consistent with the existence of two opposing effects of Ca on transmitter release. Firstly, raising the external concentration of Ca increases the electrochemical potential for Ca entry, which tends to increase Ca influx and transmitter release. Secondly, increasing external Ca concentration increases electrostatic screening of fixed negative charges on the outer surface of the nerve terminal membrane. Such an increase in screening of charges near voltage-sensitive Ca gates would produce a hyperpolarization across the gates and they would tend to close, an effect which would tend to decrease Ca influx. The monotonic increase in min. e.p.p. frequency with increasing Ca concentration in 2 mM-K is consistent with the voltage insensitivity of the Ca gates at potentials close to the normal resting potential."}
{"id": "PMID:192884", "title": "Metiamide and stimulated acid secretion from the isolated non-distended and distended mouse stomach.", "content": "1. The action of metiamide, a specific histamine H2-receptor antagonist, on the acid secretory response to various gastric stimuli in the perfused isolated whole mouse stomach is described. 2. Two kinds of stomach preparations, the non-distended stomach and distended stomach, were used. The distended stomach gave a marked and dose-related acid secretory response to histamine (10(-6) to 10(-3) M), pentagastrin (10(-8) to 10(-5) M), acetylcholine (5 X 10(-5) to 10(-5) M), eserine (10(-5) to 10(-3) M) to dibutyryl cyclic AMP (5 X 10(-5) to 10(-3) M). In the nondistended stomach, dibutyryl cyclic AMP regularly stimulated acid secretion in a dose-dependent manner; in contrast to dibutyryl cyclic AMP, histamine, pentagastrin or acetylcholine did not always stimulate acid secretion. 3. Histamine or pentagastrin but not acetylcholine always caused significant stimulation of acid secretion from the non-distended stomach in the presence of a phosphodiesterase inhibitor such as caffeine, theophylline or the I.C.I. compound, 63197. At the concentration of 10(-4) M, these phosphodiesterase inhibitors markedly potentiated the stimulatory effect of histamine or pentagastrin on acid secretion and the order of effectiveness was 63197 greater than theophylline greater than caffeine. 63197 also produced profound potentiation of histamine- or pentagastrin-stimulated acid secretion in the distended stomach. 4. Metiamide (5 X 10(-5) to 10(-4) M) did not antagonize stimulation of acid secretion by dibutyryl cyclic AMP in the non-distended or distended stomach. 5. In the distended stomach, metiamide (5 X 10(-4) M) produced significant inhibition of histamine-stimulated acid secretion with a linear and parallel displacement of the histamine dose--response curve to the right. Although at this concentration metiamide did not depress maximal acid secretory response to histamine, it caused marked reduction of the maximal acid secretory response attainable with pentagastrin. 6. In the distended stomach, metiamide (5 X 10(-5) M) did not cause significant inhibition of acetylcholine-induced acid secretion. Atropine (5 X 10(-6) M) abolished the stimulatory effect of acetylcholine; it also produced marked inhibition of pentagastrin-stimulated acid secretion but it had little effect on acid secretion induced by histamine. 7. The present results indicate that metiamide inhibited histamine-induced acid secretion by competitive antagonism of the histamine H2-receptor, but its inhibitory effect on pentagastrin-induced acid secretion seemed to be of non-competitive nature. The failure of metiamide to inhibit acid secretion induced by dibutyryl cyclic AMP suggests that cyclic AMP might regulate gastric acid secretion at a site beyond the histamine H2-receptor activation. It is also considered that the present results support the hypothesis that cyclic AMP may be involved in histamine- or pentagastrin-induced acid secretion in the isolated mouse stomach. 8...", "contents": "Metiamide and stimulated acid secretion from the isolated non-distended and distended mouse stomach. 1. The action of metiamide, a specific histamine H2-receptor antagonist, on the acid secretory response to various gastric stimuli in the perfused isolated whole mouse stomach is described. 2. Two kinds of stomach preparations, the non-distended stomach and distended stomach, were used. The distended stomach gave a marked and dose-related acid secretory response to histamine (10(-6) to 10(-3) M), pentagastrin (10(-8) to 10(-5) M), acetylcholine (5 X 10(-5) to 10(-5) M), eserine (10(-5) to 10(-3) M) to dibutyryl cyclic AMP (5 X 10(-5) to 10(-3) M). In the nondistended stomach, dibutyryl cyclic AMP regularly stimulated acid secretion in a dose-dependent manner; in contrast to dibutyryl cyclic AMP, histamine, pentagastrin or acetylcholine did not always stimulate acid secretion. 3. Histamine or pentagastrin but not acetylcholine always caused significant stimulation of acid secretion from the non-distended stomach in the presence of a phosphodiesterase inhibitor such as caffeine, theophylline or the I.C.I. compound, 63197. At the concentration of 10(-4) M, these phosphodiesterase inhibitors markedly potentiated the stimulatory effect of histamine or pentagastrin on acid secretion and the order of effectiveness was 63197 greater than theophylline greater than caffeine. 63197 also produced profound potentiation of histamine- or pentagastrin-stimulated acid secretion in the distended stomach. 4. Metiamide (5 X 10(-5) to 10(-4) M) did not antagonize stimulation of acid secretion by dibutyryl cyclic AMP in the non-distended or distended stomach. 5. In the distended stomach, metiamide (5 X 10(-4) M) produced significant inhibition of histamine-stimulated acid secretion with a linear and parallel displacement of the histamine dose--response curve to the right. Although at this concentration metiamide did not depress maximal acid secretory response to histamine, it caused marked reduction of the maximal acid secretory response attainable with pentagastrin. 6. In the distended stomach, metiamide (5 X 10(-5) M) did not cause significant inhibition of acetylcholine-induced acid secretion. Atropine (5 X 10(-6) M) abolished the stimulatory effect of acetylcholine; it also produced marked inhibition of pentagastrin-stimulated acid secretion but it had little effect on acid secretion induced by histamine. 7. The present results indicate that metiamide inhibited histamine-induced acid secretion by competitive antagonism of the histamine H2-receptor, but its inhibitory effect on pentagastrin-induced acid secretion seemed to be of non-competitive nature. The failure of metiamide to inhibit acid secretion induced by dibutyryl cyclic AMP suggests that cyclic AMP might regulate gastric acid secretion at a site beyond the histamine H2-receptor activation. It is also considered that the present results support the hypothesis that cyclic AMP may be involved in histamine- or pentagastrin-induced acid secretion in the isolated mouse stomach. 8..."}
{"id": "PMID:192885", "title": "An analysis of the action of a false transmitter at the neuromuscular junction.", "content": "1. The action of monoethylcholine (MECh) on neuromuscular transmission has been studied by electrophysiological methods. 2. End-plate potentials (e.p.p.s.) in curarized rat muscle were unaffected or slightly increased in amplitude by MECh (0-1-1 mM). Stimulation at 3 Hz for about 30 min in the presence of MECh caused a progressive decline in e.p.p. amplitude, and a shortening of the e.p.p. time course. These changes were reversed by addition of choline to the medium. Similar changes in amplitude, but no change in time course, occurred when the preparation was stimulated in the presence of hemicholinium or triethylcholine. 3. Extracellular recordings of miniature end-plate potentials in frog muscle showed that stimulation in the presence of MECh caused the time constant of the exponential decay of the m.e.p.p.s. to decrease by 42%. The amplitude of intracellular m.e.p.p.s. was reduced by 45%. These changes were maximal by the time about 3 X 10(5) quanta had been released. 4. Voltage clamp experiments in rat muscle in which miniature end-plate currents (m.e.p.c.s) were recorded showed that stimulation in the presence of MECh reduced the amplitude (by 33%) and the decay time constant (by 42%). 5. Analysis of end-plate current flucutations produced by local application of acetylcholine (ACh) and acetylmonoethycholine (AMECh) to voltage clamped rat end-plates showed that the amplitude of the elementary current events was the same for both compounds whereas the average channel lifetime was 44% shorter for AMECh than for ACh. 6. The voltage-sensitivity of the channel lifetime (measured from end-plate current fluctuations) was the same for ACh and AMECh. The voltage-sensitivity of the m.e.p.c. decay time constant was the same as that found from noise measurements. The shortened m.e.p.c.s. (false m.e.p.c.s.) occurring after stimulation in the presence of MECh also showed the same voltage-sensitivity. 7. Both normal and false m.e.p.c.s. were prolonged by neostigmine by almost the same factor; false m.e.p.c.s. were thus shorter than normal m.e.p.c.s. even when cholinesterase was inactivated. Experiments with progressive curarization of neostigmine-treated end-plates suggested that the fraction of transmitter molecules bound is smaller for false than for normal m.e.p.c.s. The difference implies that the false transmitter has one quarter of the affinity of ACh for the receptors. 8. It is concluded that stimulation in the presence of MECh gives rise to a false transmitter, presumably AMECh, which has a lower affinity for receptors than ACh, and gives rise to ionic channels with a shorter average lifetime than those activated by ACh.", "contents": "An analysis of the action of a false transmitter at the neuromuscular junction. 1. The action of monoethylcholine (MECh) on neuromuscular transmission has been studied by electrophysiological methods. 2. End-plate potentials (e.p.p.s.) in curarized rat muscle were unaffected or slightly increased in amplitude by MECh (0-1-1 mM). Stimulation at 3 Hz for about 30 min in the presence of MECh caused a progressive decline in e.p.p. amplitude, and a shortening of the e.p.p. time course. These changes were reversed by addition of choline to the medium. Similar changes in amplitude, but no change in time course, occurred when the preparation was stimulated in the presence of hemicholinium or triethylcholine. 3. Extracellular recordings of miniature end-plate potentials in frog muscle showed that stimulation in the presence of MECh caused the time constant of the exponential decay of the m.e.p.p.s. to decrease by 42%. The amplitude of intracellular m.e.p.p.s. was reduced by 45%. These changes were maximal by the time about 3 X 10(5) quanta had been released. 4. Voltage clamp experiments in rat muscle in which miniature end-plate currents (m.e.p.c.s) were recorded showed that stimulation in the presence of MECh reduced the amplitude (by 33%) and the decay time constant (by 42%). 5. Analysis of end-plate current flucutations produced by local application of acetylcholine (ACh) and acetylmonoethycholine (AMECh) to voltage clamped rat end-plates showed that the amplitude of the elementary current events was the same for both compounds whereas the average channel lifetime was 44% shorter for AMECh than for ACh. 6. The voltage-sensitivity of the channel lifetime (measured from end-plate current fluctuations) was the same for ACh and AMECh. The voltage-sensitivity of the m.e.p.c. decay time constant was the same as that found from noise measurements. The shortened m.e.p.c.s. (false m.e.p.c.s.) occurring after stimulation in the presence of MECh also showed the same voltage-sensitivity. 7. Both normal and false m.e.p.c.s. were prolonged by neostigmine by almost the same factor; false m.e.p.c.s. were thus shorter than normal m.e.p.c.s. even when cholinesterase was inactivated. Experiments with progressive curarization of neostigmine-treated end-plates suggested that the fraction of transmitter molecules bound is smaller for false than for normal m.e.p.c.s. The difference implies that the false transmitter has one quarter of the affinity of ACh for the receptors. 8. It is concluded that stimulation in the presence of MECh gives rise to a false transmitter, presumably AMECh, which has a lower affinity for receptors than ACh, and gives rise to ionic channels with a shorter average lifetime than those activated by ACh."}
{"id": "PMID:192886", "title": "Multiple unit activity recording in the corticotropic area of the deafferented hypothalamus and corticosteronemia in the pigeon.", "content": "10 Diurnal variations in both multiple unit activity and plasma corticosterone level were suppressed after complete neural isolation of the basal hypothalamus in the pigeon. 20 It is suggested that the circadian activity of the hypothalamic pituitary corticotropic unit partially depends upon the inhibiting influence from the hippocampic-septal structures.", "contents": "Multiple unit activity recording in the corticotropic area of the deafferented hypothalamus and corticosteronemia in the pigeon. 10 Diurnal variations in both multiple unit activity and plasma corticosterone level were suppressed after complete neural isolation of the basal hypothalamus in the pigeon. 20 It is suggested that the circadian activity of the hypothalamic pituitary corticotropic unit partially depends upon the inhibiting influence from the hippocampic-septal structures."}
{"id": "PMID:192887", "title": "[Inhibitory mechanisms within the receptive fields of X-and Y-type retinal ganglion cells of the cat (author's transl)].", "content": "Two-stages of the inhibitory mechanisms were assumed within the on-center receptive field (RF) of the cat's retinal ganglion cell on the basis of the following two experiments: 1) Effect of background intensity upon the magnitude of the response to the RF-centered spot of stimulus, and 2) the time course of the inhibitory effect when the additional spot of light is presented in the same RF center region. The first stage is an inhibitory feed-back from horizontal cell to the photoreceptor. Both X-and Y-fields have this feed-back route. By this gain control machanisms, the ganglion cell will respond to the intensity ratio of the spot to the background. [corrected] The second stage of inhibitory mechanism in X-field is the feed-back from sustained amacrine cell to the bipolar cell. Above two stages of feed-back mechanism in X-field explain the strong maintained suppressive effect produced by the additional spot of light. On the other hand, the Y-type ganglion cell will recive the inhibitory input via feed-forward path from trannsient amacrine cell. This explains the transient on- and of f-suppressive effects", "contents": "[Inhibitory mechanisms within the receptive fields of X-and Y-type retinal ganglion cells of the cat (author's transl)]. Two-stages of the inhibitory mechanisms were assumed within the on-center receptive field (RF) of the cat's retinal ganglion cell on the basis of the following two experiments: 1) Effect of background intensity upon the magnitude of the response to the RF-centered spot of stimulus, and 2) the time course of the inhibitory effect when the additional spot of light is presented in the same RF center region. The first stage is an inhibitory feed-back from horizontal cell to the photoreceptor. Both X-and Y-fields have this feed-back route. By this gain control machanisms, the ganglion cell will respond to the intensity ratio of the spot to the background. [corrected] The second stage of inhibitory mechanism in X-field is the feed-back from sustained amacrine cell to the bipolar cell. Above two stages of feed-back mechanism in X-field explain the strong maintained suppressive effect produced by the additional spot of light. On the other hand, the Y-type ganglion cell will recive the inhibitory input via feed-forward path from trannsient amacrine cell. This explains the transient on- and of f-suppressive effects"}
{"id": "PMID:192891", "title": "The activity of polymyxins against Escherichia coli in an in-vitro model of the urinary bladder.", "content": "The activities against a strain of Escherichia coli of polymyxin B, colistin (polymyxin E) and their sulphomethyl derivatives sulphomyxin and colistin sulphomethate have been examined in an in-vitro model of the urinary bladder under conditions similar to those that may operate in the therapeutic situation. In the dynamic conditions of the model, polymyxins exhibited a reduced activity against E. coli in comparison with activity against exponentially growing cultures in a static system. Nevertheless, long-term suppression of bacterial growth was achieved with levels of polymyxin B and colistin that can be attained during therapy, whereas sulphomethylpolymyxins had little effect on bacterial growth even on prolonged exposure.", "contents": "The activity of polymyxins against Escherichia coli in an in-vitro model of the urinary bladder. The activities against a strain of Escherichia coli of polymyxin B, colistin (polymyxin E) and their sulphomethyl derivatives sulphomyxin and colistin sulphomethate have been examined in an in-vitro model of the urinary bladder under conditions similar to those that may operate in the therapeutic situation. In the dynamic conditions of the model, polymyxins exhibited a reduced activity against E. coli in comparison with activity against exponentially growing cultures in a static system. Nevertheless, long-term suppression of bacterial growth was achieved with levels of polymyxin B and colistin that can be attained during therapy, whereas sulphomethylpolymyxins had little effect on bacterial growth even on prolonged exposure."}
{"id": "PMID:192892", "title": "Electron spin resonance studies of an animal model of human congenital myotonia: increased erythrocyte membrane fluidity in rats with 20,25-diazacholesterol-induced myotonia.", "content": "Electron spin resonance experiments have been performed on erythrocyte membranes from rats with myotonia induced by treatment with 20,25-diazacholesterol. The results suggest that erythrocyte membranes in this animal model of human congenital myotonia possess a highly significantly increased surface membrane fluidity compared to that of controls. Alterations in the physical state of membrane proteins were not apparent. These findings, also present in human congenital myotonia [Butterfield, Chesnut, Roses & Appel, 1976, Nature (London) 263:159; Butterfield, 1977 (Submitted for publication)], strengthen the concepts that increased membrane fluidity is associated with the presence of myotonia and that congenital myotonia may be a diffuse membrane disease.", "contents": "Electron spin resonance studies of an animal model of human congenital myotonia: increased erythrocyte membrane fluidity in rats with 20,25-diazacholesterol-induced myotonia. Electron spin resonance experiments have been performed on erythrocyte membranes from rats with myotonia induced by treatment with 20,25-diazacholesterol. The results suggest that erythrocyte membranes in this animal model of human congenital myotonia possess a highly significantly increased surface membrane fluidity compared to that of controls. Alterations in the physical state of membrane proteins were not apparent. These findings, also present in human congenital myotonia [Butterfield, Chesnut, Roses & Appel, 1976, Nature (London) 263:159; Butterfield, 1977 (Submitted for publication)], strengthen the concepts that increased membrane fluidity is associated with the presence of myotonia and that congenital myotonia may be a diffuse membrane disease."}
{"id": "PMID:192893", "title": "Spironolactone antagonism of aldosterone action on Na+ transport and RNA metabolism in toad bladder epithelium.", "content": "In earlier studies, aldosterone increased the incorporation of precursors into a class of cytoplasmic RNA with the characteristics of messenger RNA (mRNA), in toad bladder epithelium. In the present studies, this effect was analyzed further with a competitive antagonist, spironolactone (SC-9420). Paired hemibladders were labeled with 3H-uridine (30 min pulse - 140 min chase), with or without aldosterone (3.5 x 10(-8) M, 7 X 10(-8) M) in the presence or absence of SC-9420 (7 X 10(-6) M, 2.5 X 10(-5) M) at molar ratios of 200:1 to 280:1. Cytoplasmic RNA, either the total phenol-SDS extract or polyadenylated-RNA (poly(A)(+)-RNA) obtained by oligo-deoxythymidylate-cellulose (oligo(dT)-cellulose) chromatography was analyzed in linear 5 -- 20% sucrose gradients. Eight sets of experiments were completed in which the short-circuit current (scc) was monitored for 180 min and the incorporation of 3H-uridine (30 min pulse -- 150 min chase) was simultaneously determined on pools of epithelia from 5 to 10 hemibladders. The fractional change in scc correlated linearly with the fractional change in 3H-uridine of 12S cytoplasmic RNA (r=0.95, p less than 0.001). The poly(A)(+)-RNA fraction had no detectable rRNA or tRNA and gave a heterogeneous pattern, typical of mRNA, in the sucrose gradients. In the presence of exogenous aldosterone, SC-9420 inhibited the incorporation of 3H-uridine into poly(A)(+)-RNA (particularly 12S). These results support the inference that induction of mRNA mediates the action of aldosterone on Na+ transport.", "contents": "Spironolactone antagonism of aldosterone action on Na+ transport and RNA metabolism in toad bladder epithelium. In earlier studies, aldosterone increased the incorporation of precursors into a class of cytoplasmic RNA with the characteristics of messenger RNA (mRNA), in toad bladder epithelium. In the present studies, this effect was analyzed further with a competitive antagonist, spironolactone (SC-9420). Paired hemibladders were labeled with 3H-uridine (30 min pulse - 140 min chase), with or without aldosterone (3.5 x 10(-8) M, 7 X 10(-8) M) in the presence or absence of SC-9420 (7 X 10(-6) M, 2.5 X 10(-5) M) at molar ratios of 200:1 to 280:1. Cytoplasmic RNA, either the total phenol-SDS extract or polyadenylated-RNA (poly(A)(+)-RNA) obtained by oligo-deoxythymidylate-cellulose (oligo(dT)-cellulose) chromatography was analyzed in linear 5 -- 20% sucrose gradients. Eight sets of experiments were completed in which the short-circuit current (scc) was monitored for 180 min and the incorporation of 3H-uridine (30 min pulse -- 150 min chase) was simultaneously determined on pools of epithelia from 5 to 10 hemibladders. The fractional change in scc correlated linearly with the fractional change in 3H-uridine of 12S cytoplasmic RNA (r=0.95, p less than 0.001). The poly(A)(+)-RNA fraction had no detectable rRNA or tRNA and gave a heterogeneous pattern, typical of mRNA, in the sucrose gradients. In the presence of exogenous aldosterone, SC-9420 inhibited the incorporation of 3H-uridine into poly(A)(+)-RNA (particularly 12S). These results support the inference that induction of mRNA mediates the action of aldosterone on Na+ transport."}
{"id": "PMID:192894", "title": "Epstein-Barr virus genome studies in Burkitt's and non-Burkitt's lymphomas in Uganda.", "content": "Burkitt's lymphoma (BL) has been widely investigated and has attracted attention because of the possible etiologic role of the Epstein-Barr virus (EBV). To further determine the role of EBV in the causation of this tumor, we measured EBV-specific nuclear antigen (EBNA) and EBV DNA using immunofluorescence and nucleic acid hybridization techniques, respectively. Of 34 BL biopsies, 27 tissues (79%) were EBNA-positive, whereas none of the 25 non-BL biopsy tissues were EBNA-positive. Of 15 BL tumors tested, 14 (93%) were EBV DNA-positive with a mean of 39 (range, 8-86) EBV genome equivalents per cell. Each of the 15 non-BL biopsy specimens subjected to nucleic acid hybridization had less than two virus genome equivalents per cell, although all had serologic evidence of past EBV infection. The findings further supported the possible etiologic role of EBV in African BL and negated the passenger hypothesis. The EBV genome could, therefore, be used as a separating marker between African BL and non-BL lymphomas.", "contents": "Epstein-Barr virus genome studies in Burkitt's and non-Burkitt's lymphomas in Uganda. Burkitt's lymphoma (BL) has been widely investigated and has attracted attention because of the possible etiologic role of the Epstein-Barr virus (EBV). To further determine the role of EBV in the causation of this tumor, we measured EBV-specific nuclear antigen (EBNA) and EBV DNA using immunofluorescence and nucleic acid hybridization techniques, respectively. Of 34 BL biopsies, 27 tissues (79%) were EBNA-positive, whereas none of the 25 non-BL biopsy tissues were EBNA-positive. Of 15 BL tumors tested, 14 (93%) were EBV DNA-positive with a mean of 39 (range, 8-86) EBV genome equivalents per cell. Each of the 15 non-BL biopsy specimens subjected to nucleic acid hybridization had less than two virus genome equivalents per cell, although all had serologic evidence of past EBV infection. The findings further supported the possible etiologic role of EBV in African BL and negated the passenger hypothesis. The EBV genome could, therefore, be used as a separating marker between African BL and non-BL lymphomas."}
{"id": "PMID:192895", "title": "Hepatitis B virus infection and primary hepatocellular carcinoma.", "content": "Ninety-three patients with biopsy-proven primary hepatocellular carcinoma (PHC) from Uganda, Zambia, and the United States were examined for serologic evidence of hepatitis B virus (HBV) infection. Patients were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs), antibody to the hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg), and its antibody (anti-HBe). Active HBV infection, as indicated by positive tests for HBsAg (with or without anti-HBs) and anti-HBc (without anti-HBs), was present in 62% of PHC patients (58 of 93), in contrast with 10% of African controls (9 of 90), and less than 1% of most United States adult populations reported in the literature. The presence of HBeAg or anti-HBe was rare among PHC patients and controls.", "contents": "Hepatitis B virus infection and primary hepatocellular carcinoma. Ninety-three patients with biopsy-proven primary hepatocellular carcinoma (PHC) from Uganda, Zambia, and the United States were examined for serologic evidence of hepatitis B virus (HBV) infection. Patients were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs), antibody to the hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg), and its antibody (anti-HBe). Active HBV infection, as indicated by positive tests for HBsAg (with or without anti-HBs) and anti-HBc (without anti-HBs), was present in 62% of PHC patients (58 of 93), in contrast with 10% of African controls (9 of 90), and less than 1% of most United States adult populations reported in the literature. The presence of HBeAg or anti-HBe was rare among PHC patients and controls."}
{"id": "PMID:192896", "title": "A solid-phase radioimmunoassay for Epstein-Barr virus-associated membrane antigen prepared from B95-8 cell culture supernatants.", "content": "Epstein-Barr virus(EBV)-associated membrane antigen (MA) was concentrated from B95-8 cell culture media by precipitation with polyethylene glycol followed by chromatography on Bio-Gel A-50m. In a RAJI cell-binding assay, MA-positive material could only be found in the void volume of the column. After ultracentrifugation all antigenic activity appeared in the pellet, which suggested that MA was present in aggregates, presumably fragments of cellular membranes and/or virus envelopes. The MA-containing preparation was photopolymerized in polyacrylamide gel. The homogenized gel was used in a solidphase radioimmunoassay with 125l-labeled IgG from an Anti-MA positive reference serum and an anti-MA negative control serum. The specificity of the reaction was confirmed in blocking tests with anti-EBV positive and negative sera. A good correlation was found between the results obtained in the radioimmunoassay and the results obtained in direct immunofluorescence tests for the detection of MA. The existence of at least two subspecificities of the MA complex could be confirmed by this radioimmunoassay.", "contents": "A solid-phase radioimmunoassay for Epstein-Barr virus-associated membrane antigen prepared from B95-8 cell culture supernatants. Epstein-Barr virus(EBV)-associated membrane antigen (MA) was concentrated from B95-8 cell culture media by precipitation with polyethylene glycol followed by chromatography on Bio-Gel A-50m. In a RAJI cell-binding assay, MA-positive material could only be found in the void volume of the column. After ultracentrifugation all antigenic activity appeared in the pellet, which suggested that MA was present in aggregates, presumably fragments of cellular membranes and/or virus envelopes. The MA-containing preparation was photopolymerized in polyacrylamide gel. The homogenized gel was used in a solidphase radioimmunoassay with 125l-labeled IgG from an Anti-MA positive reference serum and an anti-MA negative control serum. The specificity of the reaction was confirmed in blocking tests with anti-EBV positive and negative sera. A good correlation was found between the results obtained in the radioimmunoassay and the results obtained in direct immunofluorescence tests for the detection of MA. The existence of at least two subspecificities of the MA complex could be confirmed by this radioimmunoassay."}
{"id": "PMID:192897", "title": "Epidemiology of cancer of the testis in upstate New York.", "content": "We collected data on the 434 individuals reported with cancer of the testis to the New York State Tumor Registry, 1960-64, from upstate New York. We compared these with the 410 members of a random sample of the upstate population interviewed from 1959 to 1962. A high risk of developing cancer of the testis was associated with professional occupations, native-born parentage, rural residence, and having been married, especially while young. These findings paralleled some other studies, as well as our earlier inquiry. Each of these factors carried a higher risk even when considered in the context of the other traits, and risk increased with an increase in the number of characteristics possessed.", "contents": "Epidemiology of cancer of the testis in upstate New York. We collected data on the 434 individuals reported with cancer of the testis to the New York State Tumor Registry, 1960-64, from upstate New York. We compared these with the 410 members of a random sample of the upstate population interviewed from 1959 to 1962. A high risk of developing cancer of the testis was associated with professional occupations, native-born parentage, rural residence, and having been married, especially while young. These findings paralleled some other studies, as well as our earlier inquiry. Each of these factors carried a higher risk even when considered in the context of the other traits, and risk increased with an increase in the number of characteristics possessed."}
{"id": "PMID:192898", "title": "Activation of Epstein-Barr virus in hybrid cells.", "content": "Human-primate hybrid cell lines were established by fusion of African green monkey kidney cells (VERO) with lymphoblastoid cells from patients with infectious mononucleosis (IM)(IMK101) and from Burkitt's lymphoma culture (HR1K). Both Epstein-Barr virus (EBV)-specific antigens and EBV particle-containing cells increased in the hybrid lines (IMK1-1/VERO,HR1K/VERO). Treatment of the hybrids with 5-bromodeoxyuridine induced more antigen-positive and more virus-containing cells. EBV could be activated from IM lymphoblastoid cells by fusion of the lymphoblastoid cells with the VERO cells. The increase of viral antigens and virus particles may have been due to the cellular interaction between VERO cells and the lymphoblastoid cells or to a possible derepressor supplied by the VERO component of the hybrid. Virus derived from the HR1K cell line was replicated in the human-primate hybrid, but further investigation may be necessary to determine if it was identical to the EBV derived from the human cell line.", "contents": "Activation of Epstein-Barr virus in hybrid cells. Human-primate hybrid cell lines were established by fusion of African green monkey kidney cells (VERO) with lymphoblastoid cells from patients with infectious mononucleosis (IM)(IMK101) and from Burkitt's lymphoma culture (HR1K). Both Epstein-Barr virus (EBV)-specific antigens and EBV particle-containing cells increased in the hybrid lines (IMK1-1/VERO,HR1K/VERO). Treatment of the hybrids with 5-bromodeoxyuridine induced more antigen-positive and more virus-containing cells. EBV could be activated from IM lymphoblastoid cells by fusion of the lymphoblastoid cells with the VERO cells. The increase of viral antigens and virus particles may have been due to the cellular interaction between VERO cells and the lymphoblastoid cells or to a possible derepressor supplied by the VERO component of the hybrid. Virus derived from the HR1K cell line was replicated in the human-primate hybrid, but further investigation may be necessary to determine if it was identical to the EBV derived from the human cell line."}
{"id": "PMID:192899", "title": "Ultracytochemical localization of glucose-6-phosphatase in Chang rat hepatoma in vivo and in vitro.", "content": "The standard lead precipitation method was used for ultracytochemical localization of glucose-6-phosphatase (G-6-Pase) in the in vivo and in vitro forms of the Chang rat hepatoma and in the normal adult rat liver. Reaction product was visualized as very fine particulate within the cisternae of the nuclear envelope and endoplasmic reticulum. Cytochemically, the amount of the G-6-Pase reaction product in both forms of the tumor cells was obviously less than that in the normal hepatocytes. Apparently, the enzyme was not completely deleted from the hepatoma cells. The results supported some biochemical data of certain other hepatomas. The successful ultracytochemical localization of G-6-Pase in cultured hepatoma cells has not been reported previously.", "contents": "Ultracytochemical localization of glucose-6-phosphatase in Chang rat hepatoma in vivo and in vitro. The standard lead precipitation method was used for ultracytochemical localization of glucose-6-phosphatase (G-6-Pase) in the in vivo and in vitro forms of the Chang rat hepatoma and in the normal adult rat liver. Reaction product was visualized as very fine particulate within the cisternae of the nuclear envelope and endoplasmic reticulum. Cytochemically, the amount of the G-6-Pase reaction product in both forms of the tumor cells was obviously less than that in the normal hepatocytes. Apparently, the enzyme was not completely deleted from the hepatoma cells. The results supported some biochemical data of certain other hepatomas. The successful ultracytochemical localization of G-6-Pase in cultured hepatoma cells has not been reported previously."}
{"id": "PMID:192900", "title": "Lamella-particle complexes in nuclei of owl monkey kidney cells infected with herpesvirus saimiri.", "content": "A complex consisting of ribosome-like particles and a striated lamella occurring in stacked, tubular, and twisted ribbon-like configurations was observed in the nuclei of confluent monolayer cultures of primary owl monkey kidney cells infected with Herpesvirus saimiri. They were similar to the cytoplasmic cylindroid structures seen in some human leukemias and in the lymphoma of the northern pike.", "contents": "Lamella-particle complexes in nuclei of owl monkey kidney cells infected with herpesvirus saimiri. A complex consisting of ribosome-like particles and a striated lamella occurring in stacked, tubular, and twisted ribbon-like configurations was observed in the nuclei of confluent monolayer cultures of primary owl monkey kidney cells infected with Herpesvirus saimiri. They were similar to the cytoplasmic cylindroid structures seen in some human leukemias and in the lymphoma of the northern pike."}
{"id": "PMID:192901", "title": "Degradation of basement membrane by murine tumor cells.", "content": "Tumor cells from the murine T241 fibrosarcoma, which rapidly and reproducibility produces pulmonary metastases, were tested in vitro for their ability to degrade isolated pulmonary basement membrane. Degradation of basement membrane substrate was quantified by the culture of the substrate with tumor cells and measurement of the solubilized hydroxyproline and hexose glycoprotein at neutral pH. It was found that tumor cells collected in the tumor venous drainage were associated with a significantly greater solubilization of basement membrane than were tumor cells obtained from the primary tumor mass. Tumor cells were also assayed for their ability to solubilize type I collagen purified from human dura. Venous effluent tumor cells solubilized collagen to a significantly greater level than primary tumor cells, spleen cells, or liver cells. These findings raised the possibility that metastasizing tumor cells may be a distinct tumor subpopulation with regard to invasive potential.", "contents": "Degradation of basement membrane by murine tumor cells. Tumor cells from the murine T241 fibrosarcoma, which rapidly and reproducibility produces pulmonary metastases, were tested in vitro for their ability to degrade isolated pulmonary basement membrane. Degradation of basement membrane substrate was quantified by the culture of the substrate with tumor cells and measurement of the solubilized hydroxyproline and hexose glycoprotein at neutral pH. It was found that tumor cells collected in the tumor venous drainage were associated with a significantly greater solubilization of basement membrane than were tumor cells obtained from the primary tumor mass. Tumor cells were also assayed for their ability to solubilize type I collagen purified from human dura. Venous effluent tumor cells solubilized collagen to a significantly greater level than primary tumor cells, spleen cells, or liver cells. These findings raised the possibility that metastasizing tumor cells may be a distinct tumor subpopulation with regard to invasive potential."}
{"id": "PMID:192902", "title": "Heterogeneity of karyotype and growth potential in simian virus 40-transformed Chinese hamster cell clones.", "content": "Five clones of Chinese hamster cells transformed with simian virus 40 (SV40) were isolated from methylcellulose and characterized as to Giemsa-banded karyotype, DNA content, saturation density, agglutination with concanavalin A, and tumorigenicity. Chromosome analysis and DNA content studies at early passage revealed that the genetic complement for all clones was predominantly near tetraploid. All cultures examined contained a proportion of hypertetraploid cells. Nonrandom chromosome changes included at least one broken No 1 chromosone in 80% or more of the cells in each clone, and fewer sex chromosomes than anticipated from the ploidy of the cells. Several abnormal marker chromosomes tended to recur. These changes were more pronounced in the cells cultured from tumors formed by three of the clones. A karyotypically stable stem line was not noted for any of the clones or tumors. The functional significance of the karyotypic heterogeneity was assessed by means of cloning efficiencies both on plastic and in methylcellulose.", "contents": "Heterogeneity of karyotype and growth potential in simian virus 40-transformed Chinese hamster cell clones. Five clones of Chinese hamster cells transformed with simian virus 40 (SV40) were isolated from methylcellulose and characterized as to Giemsa-banded karyotype, DNA content, saturation density, agglutination with concanavalin A, and tumorigenicity. Chromosome analysis and DNA content studies at early passage revealed that the genetic complement for all clones was predominantly near tetraploid. All cultures examined contained a proportion of hypertetraploid cells. Nonrandom chromosome changes included at least one broken No 1 chromosone in 80% or more of the cells in each clone, and fewer sex chromosomes than anticipated from the ploidy of the cells. Several abnormal marker chromosomes tended to recur. These changes were more pronounced in the cells cultured from tumors formed by three of the clones. A karyotypically stable stem line was not noted for any of the clones or tumors. The functional significance of the karyotypic heterogeneity was assessed by means of cloning efficiencies both on plastic and in methylcellulose."}
{"id": "PMID:192903", "title": "Nucleotide-induced inhibition of surface sialyl transferase activity on cultured Burkitt's lymphoma cells.", "content": "Sialyl transferase activity was demonstrated on the surfaces of intact, cultured lymphoblastoid cells (RAJI) derived from a Burkitt's lymphoma. Pretreatment of the cells with neuraminidase increased the labeled sialoprotein by severalfold. A nunber of nucleotides were effective in decreasing the amount of sialoprotein assembly. CMP was the most effective inhibitor. UMP, AMP, and GMP were also inhibitory, but to a lesser degree. The diphosphate derivatives were similarly inhibitory, but generally less active than their monophosphate counterparts. The cyclic nucleotides were the least effective of all nucleotides tested; cCMP and cAMP showed a small degree of activity, whereas cUMP and cGMP were without effect. These studies indicated that a number of noncyclic and cyclic nucleotides can influence the activity of the sialyl transferase system.", "contents": "Nucleotide-induced inhibition of surface sialyl transferase activity on cultured Burkitt's lymphoma cells. Sialyl transferase activity was demonstrated on the surfaces of intact, cultured lymphoblastoid cells (RAJI) derived from a Burkitt's lymphoma. Pretreatment of the cells with neuraminidase increased the labeled sialoprotein by severalfold. A nunber of nucleotides were effective in decreasing the amount of sialoprotein assembly. CMP was the most effective inhibitor. UMP, AMP, and GMP were also inhibitory, but to a lesser degree. The diphosphate derivatives were similarly inhibitory, but generally less active than their monophosphate counterparts. The cyclic nucleotides were the least effective of all nucleotides tested; cCMP and cAMP showed a small degree of activity, whereas cUMP and cGMP were without effect. These studies indicated that a number of noncyclic and cyclic nucleotides can influence the activity of the sialyl transferase system."}
{"id": "PMID:192904", "title": "Concanavalin A and the production of bovine leukemia virus antigen in short-term lymphocyte cultures.", "content": "The influence of the mitogen concanavalin A (Con A) on the production of bovine leukemia virus (BLV) antigen in short-term lymphocyte cultures was determined by means of a single radial immunodiffusion test. Con A did not affect viral antigen production in peripheral blood lymphocytes from 60% of both experimentally and naturally infected cattle. Antigen production was stimulated by Con A in lymphocytes from 28% of the cattle, but it was inhibited in lymphocytes from 12%. Similar results were also obtained with lymphocytes from both blood and lymph nodes from 10 cattle with lymphosarcoma and from 10 clinically normal cattle with histologically normal lymph nodes. In sheep and goats, Con A had no effect on lymphocytes from 50%, stimulated BLV production in 43%, and inhibited BLV production in 7%. These results indicated that lymphocytes should be cultured with and without Con A to identify every BLV-infected animal.", "contents": "Concanavalin A and the production of bovine leukemia virus antigen in short-term lymphocyte cultures. The influence of the mitogen concanavalin A (Con A) on the production of bovine leukemia virus (BLV) antigen in short-term lymphocyte cultures was determined by means of a single radial immunodiffusion test. Con A did not affect viral antigen production in peripheral blood lymphocytes from 60% of both experimentally and naturally infected cattle. Antigen production was stimulated by Con A in lymphocytes from 28% of the cattle, but it was inhibited in lymphocytes from 12%. Similar results were also obtained with lymphocytes from both blood and lymph nodes from 10 cattle with lymphosarcoma and from 10 clinically normal cattle with histologically normal lymph nodes. In sheep and goats, Con A had no effect on lymphocytes from 50%, stimulated BLV production in 43%, and inhibited BLV production in 7%. These results indicated that lymphocytes should be cultured with and without Con A to identify every BLV-infected animal."}
{"id": "PMID:192905", "title": "Macrophage-mediated in vitro sensitization of T-lymphocytes. I; Detection of murine leukemia virus-associated antigens.", "content": "Cytotoxic effector T-lymphocytes were produced in vitro by sensitization of spleen cells on monolayers of syngeneic macrophages that had been fed with radiation leukemia virus-containing cell extracts or with supernatants of virus-producing cell cultures. The sensitized lymphocytes were cytotoxic to cell lines that expressed viral antigens. Secondary mouse embryo fibroblasts were little affected. Sensitization via macrophages appeared to be a useful system for identification of viral antigens on surfaces of various target cells, as well as for tests of the protective effect of such lymphocytes against tumor growth in vivo.", "contents": "Macrophage-mediated in vitro sensitization of T-lymphocytes. I; Detection of murine leukemia virus-associated antigens. Cytotoxic effector T-lymphocytes were produced in vitro by sensitization of spleen cells on monolayers of syngeneic macrophages that had been fed with radiation leukemia virus-containing cell extracts or with supernatants of virus-producing cell cultures. The sensitized lymphocytes were cytotoxic to cell lines that expressed viral antigens. Secondary mouse embryo fibroblasts were little affected. Sensitization via macrophages appeared to be a useful system for identification of viral antigens on surfaces of various target cells, as well as for tests of the protective effect of such lymphocytes against tumor growth in vivo."}
{"id": "PMID:192906", "title": "Liver and skeletal muscle mitochondrial function following burn injury.", "content": "The possibility of altered mitochondrial function consequent to burn injury was investigated. Mitochondria isolated from liver or skeletal muscle of burn-injured rats (20% tbs) were compared at 3 days postburn to shams and normal controls. Mitochondrial yields were the same for all groups. ADP;O ratios were in the theoretical ranges expected and did not differ among burn, sham, and normal animals. Respiratory control ratios (RCR's) were decreased in liver mitochondria, averaging 71.7% of normal for burned animals compared to 95.8% for the sham group. The loss of respiratory control in liver mitochondria implies inefficient use of substrate chemical energy and could contribute to postburn hypermetabolism. The different response of muscle mitochondria as compared to liver suggests that alterations may be organ specific.", "contents": "Liver and skeletal muscle mitochondrial function following burn injury. The possibility of altered mitochondrial function consequent to burn injury was investigated. Mitochondria isolated from liver or skeletal muscle of burn-injured rats (20% tbs) were compared at 3 days postburn to shams and normal controls. Mitochondrial yields were the same for all groups. ADP;O ratios were in the theoretical ranges expected and did not differ among burn, sham, and normal animals. Respiratory control ratios (RCR's) were decreased in liver mitochondria, averaging 71.7% of normal for burned animals compared to 95.8% for the sham group. The loss of respiratory control in liver mitochondria implies inefficient use of substrate chemical energy and could contribute to postburn hypermetabolism. The different response of muscle mitochondria as compared to liver suggests that alterations may be organ specific."}
{"id": "PMID:192908", "title": "Solubilization of the Epstein-Barr virus-determined nuclear antigen and its characterization as a DNA-binding protein.", "content": "The Eptstein-Barr virus (EBV)-determined nuclear antigen (EBNA) was solubilized from isolate nuclei of two EBV-transformed cell lines- Raji and AW-Ramos, by high-salt treatment. Its DNA-binding properties were studied by DNA-cellulose chromatography and a 51Cr release complement fixation assay. EBNA binds to both double-stranded and single-stranded calf thymus DNA, showing a higher affinity to double-stranded DNA. There was no detectable difference in the DNA binding of EBNA prepared from Raji and AW-Ramos cells.", "contents": "Solubilization of the Epstein-Barr virus-determined nuclear antigen and its characterization as a DNA-binding protein. The Eptstein-Barr virus (EBV)-determined nuclear antigen (EBNA) was solubilized from isolate nuclei of two EBV-transformed cell lines- Raji and AW-Ramos, by high-salt treatment. Its DNA-binding properties were studied by DNA-cellulose chromatography and a 51Cr release complement fixation assay. EBNA binds to both double-stranded and single-stranded calf thymus DNA, showing a higher affinity to double-stranded DNA. There was no detectable difference in the DNA binding of EBNA prepared from Raji and AW-Ramos cells."}
{"id": "PMID:192909", "title": "Polyacrylamide gel electrophoretic analysis of herpes simplex virus type 1 immunoprecipitates obtained by quantitative immunoelectrophoresis in antibody-containing agarose gel.", "content": "Crossed immunoelectrophoresis was used to characterize herpes simplex virus type 1 (HSV-1) antigens produced by infected HEp-2 cells. We report on a method for analyzing the polypeptide content in individual antigen-antibody precipitates eluted from the second-dimensional agarose gel. Four glycoprotein antigens of HSV-1, Ag-8, Ag-11, Ag-6, and Ag-3, were isolated and analyzed for polypeptide content. The molecular weights of the polypeptides are presented.", "contents": "Polyacrylamide gel electrophoretic analysis of herpes simplex virus type 1 immunoprecipitates obtained by quantitative immunoelectrophoresis in antibody-containing agarose gel. Crossed immunoelectrophoresis was used to characterize herpes simplex virus type 1 (HSV-1) antigens produced by infected HEp-2 cells. We report on a method for analyzing the polypeptide content in individual antigen-antibody precipitates eluted from the second-dimensional agarose gel. Four glycoprotein antigens of HSV-1, Ag-8, Ag-11, Ag-6, and Ag-3, were isolated and analyzed for polypeptide content. The molecular weights of the polypeptides are presented."}
{"id": "PMID:192910", "title": "Inhibition of viral RNA methylation in herpes simplex virus type 1-infected cells by 5' S-isobutyl-adenosine.", "content": "5' S-isobutyl-adenosine (SIBA), a structural analogue of S-adenosylhomocysteine, reversibly blocks the multiplication of herpes simplex type 1 virus. In the presence of SIBA, viral protein synthesis is inhibited. After removing SIBA the synthesis of proteins starts rapidly again. The new polypeptides are mainly alpha proteins (Honess and Roizman, J. Virol. 14:8-19, 1974,), normally the first to be synthesized after infection. The rapid synthesis of proteins after release of inhibition seems to be directed by mRNA formed in the presence of SIBA as indicated by experiments using actinomycin D but which was undermethylated as shown by analysis of methyl groups on RNA. SIBA inhibits the methylation of mRNA and especially that of the 5' cap. Capping of mRNA thus seems to be essential for efficient translation. The analogue affected various methylations to different extents.", "contents": "Inhibition of viral RNA methylation in herpes simplex virus type 1-infected cells by 5' S-isobutyl-adenosine. 5' S-isobutyl-adenosine (SIBA), a structural analogue of S-adenosylhomocysteine, reversibly blocks the multiplication of herpes simplex type 1 virus. In the presence of SIBA, viral protein synthesis is inhibited. After removing SIBA the synthesis of proteins starts rapidly again. The new polypeptides are mainly alpha proteins (Honess and Roizman, J. Virol. 14:8-19, 1974,), normally the first to be synthesized after infection. The rapid synthesis of proteins after release of inhibition seems to be directed by mRNA formed in the presence of SIBA as indicated by experiments using actinomycin D but which was undermethylated as shown by analysis of methyl groups on RNA. SIBA inhibits the methylation of mRNA and especially that of the 5' cap. Capping of mRNA thus seems to be essential for efficient translation. The analogue affected various methylations to different extents."}
{"id": "PMID:192911", "title": "Isolation and comparison of murine leukemia virus-related glycoproteins from AKR and New Zealand mice.", "content": "The major glycoprotein (gp70) of murine leukemia virus occurs free of virus in the serum and body fluids of certain strains of mice. These glycoproteins were isolated from New Zealand Black mouse (NZB) ascites fluid and from AKR and New Zealand White mouse (NZW) serum by immunoaffinity chromatography and were compared by immunological tests and peptide mapping. Glycoproteins gp70-NZB and gp70-NZW were indistinguishable by all criteria tested and were more closely related to gp70 from Moloney leukemia virus than was gp70-AKR.", "contents": "Isolation and comparison of murine leukemia virus-related glycoproteins from AKR and New Zealand mice. The major glycoprotein (gp70) of murine leukemia virus occurs free of virus in the serum and body fluids of certain strains of mice. These glycoproteins were isolated from New Zealand Black mouse (NZB) ascites fluid and from AKR and New Zealand White mouse (NZW) serum by immunoaffinity chromatography and were compared by immunological tests and peptide mapping. Glycoproteins gp70-NZB and gp70-NZW were indistinguishable by all criteria tested and were more closely related to gp70 from Moloney leukemia virus than was gp70-AKR."}
{"id": "PMID:192912", "title": "Biological and biochemical studies of cells transformed by simian virus 40 temperature-sensitive gene A mutants and A mutant revertants.", "content": "The growth properties of hamster cells transformed by wild-type Simian virus 40 (SV40), by early SV40 temperature-sensitive mutants of the A complementation group, and by spontaneous revertants of these mutants were studied. All of the tsA mutant-transformed cells were temperature sensitive in their ability to form clones in soft agar and on monolayers of normal cells except for CHLA-30L1, which was not temperature sensitive in the latter property. All cells transformed by stable revertants of well-characterized tsA mutants possessed certain growth properties in common with wild-type-transformed cells at both temperatures. Virus rescued from tsA transformants including CHLA30L1 was temperature sensitive for viral DNA replication, whereas that rescued from revertant and wild-type transformants was not thermolabile in this regard. T antigen present in crude extracts of tsA-transformed cells including CHLA30L1, grown at 33 degreeC, was temperature sensitive by in vitro immunoassay, whereas that from wild-type-transformed cells was relatively stable. T antigen from revertant transformants was more stable than the tsA protein. Partially purified T antigen from revertant-transformed cells was nearly as stable as wild-type antigen in its ability to bind DNA after heating at 44 degrees C, whereas T antigen from tsA30 mutant-transformed cells was relatively thermolabile. These results further indicate that T antigen is a product of the SV40 A gene. Significantly more T antigen was found in extracts of CHLA30L1 grown to high density at the nonpermissive temperature than in any other tsA-transformed cell similarly grown. This is consistent with the suggestion that the amount of T antigen synthesized in CHLA30L1 is large enoughto allow partial expression of the transformed phenotype at the restrictive temperature. Alternatively, the increase in T antigen concentration may be secondary to one or more genetic alterations that independently affect the transformed phenotype of these cells.", "contents": "Biological and biochemical studies of cells transformed by simian virus 40 temperature-sensitive gene A mutants and A mutant revertants. The growth properties of hamster cells transformed by wild-type Simian virus 40 (SV40), by early SV40 temperature-sensitive mutants of the A complementation group, and by spontaneous revertants of these mutants were studied. All of the tsA mutant-transformed cells were temperature sensitive in their ability to form clones in soft agar and on monolayers of normal cells except for CHLA-30L1, which was not temperature sensitive in the latter property. All cells transformed by stable revertants of well-characterized tsA mutants possessed certain growth properties in common with wild-type-transformed cells at both temperatures. Virus rescued from tsA transformants including CHLA30L1 was temperature sensitive for viral DNA replication, whereas that rescued from revertant and wild-type transformants was not thermolabile in this regard. T antigen present in crude extracts of tsA-transformed cells including CHLA30L1, grown at 33 degreeC, was temperature sensitive by in vitro immunoassay, whereas that from wild-type-transformed cells was relatively stable. T antigen from revertant transformants was more stable than the tsA protein. Partially purified T antigen from revertant-transformed cells was nearly as stable as wild-type antigen in its ability to bind DNA after heating at 44 degrees C, whereas T antigen from tsA30 mutant-transformed cells was relatively thermolabile. These results further indicate that T antigen is a product of the SV40 A gene. Significantly more T antigen was found in extracts of CHLA30L1 grown to high density at the nonpermissive temperature than in any other tsA-transformed cell similarly grown. This is consistent with the suggestion that the amount of T antigen synthesized in CHLA30L1 is large enoughto allow partial expression of the transformed phenotype at the restrictive temperature. Alternatively, the increase in T antigen concentration may be secondary to one or more genetic alterations that independently affect the transformed phenotype of these cells."}
{"id": "PMID:192913", "title": "Purification of hepatitis A virus from chimpanzee stools.", "content": "Hepatitis A virus antigen was purified from early acute-phase chimpanzee stools by a rapid three-step procedure using 7% polyethylene glycol precipitation, CsCl banding, and Sepharose 2B column chromatography. Electron microscopic examination of the hepatitis A virus entigen preparation revealed highly purified hepatitis A virus particles.", "contents": "Purification of hepatitis A virus from chimpanzee stools. Hepatitis A virus antigen was purified from early acute-phase chimpanzee stools by a rapid three-step procedure using 7% polyethylene glycol precipitation, CsCl banding, and Sepharose 2B column chromatography. Electron microscopic examination of the hepatitis A virus entigen preparation revealed highly purified hepatitis A virus particles."}
{"id": "PMID:192914", "title": "Inverted repetition in the chromosome of pseudorabies virus.", "content": "An electron microscope examination of pseudorabies virus DNA single strands after self-annealing shows a loop of single-stranded DNA at one end of the molecule contiguous to a double-strand region. The molecule then terminates in a further single-stranded region that does not form a loop. It is suggested that the DNA contains a sequence of 13.3 x 106 daltons at one end, which is repeated internally with opposite polarity. The segment of the genome separating the repeats has a double-strand molecular weight of 5.4 x 106. The whole native DNA has a molecular weight of 90 x 106 to 95 x 106.", "contents": "Inverted repetition in the chromosome of pseudorabies virus. An electron microscope examination of pseudorabies virus DNA single strands after self-annealing shows a loop of single-stranded DNA at one end of the molecule contiguous to a double-strand region. The molecule then terminates in a further single-stranded region that does not form a loop. It is suggested that the DNA contains a sequence of 13.3 x 106 daltons at one end, which is repeated internally with opposite polarity. The segment of the genome separating the repeats has a double-strand molecular weight of 5.4 x 106. The whole native DNA has a molecular weight of 90 x 106 to 95 x 106."}
{"id": "PMID:192915", "title": "Strandedness of Pichinde virus RNA.", "content": "The Pichinde virus RNA did not possess the following characteristics of eucaryotic mRNA: polyadenylic acid sequence, capped methylated structure, and ability to direct protein synthesis in vitro. Polysomal RNA extracted from cells infected with Pichinde virus reannealed with 32P-labeled virus RNA, protecting about 60% of the latter against RNase degestion. The polyadenylic acid-containing polysomal RNA also reannealed to the 32P-labeled virus RNA to approximately the same extent. These indicate that the major part of the genomic RNA of Pichinde virus is negative stranded.", "contents": "Strandedness of Pichinde virus RNA. The Pichinde virus RNA did not possess the following characteristics of eucaryotic mRNA: polyadenylic acid sequence, capped methylated structure, and ability to direct protein synthesis in vitro. Polysomal RNA extracted from cells infected with Pichinde virus reannealed with 32P-labeled virus RNA, protecting about 60% of the latter against RNase degestion. The polyadenylic acid-containing polysomal RNA also reannealed to the 32P-labeled virus RNA to approximately the same extent. These indicate that the major part of the genomic RNA of Pichinde virus is negative stranded."}
{"id": "PMID:192916", "title": "Virus-secific transcription in 3T3 cells transformed by the ts-a mutant of polyoma virus.", "content": "Virus-specific RNA transcription has been measured in 3T3 cells transformed by the ts-a mutant of polyoma virus by RNA-excess hybridization to the separated strands of polyoma DNA. In two cloned sublines maintained at 39 degrees C, the nonpermissive temperature for the A gene function, RNA transcripts of a large fraction of the \"early\" strand are detected in both nuclear and cytoplasmic RNA fractions, but no \"late\" strand transcription is detected. Temperature shift to 31.5 degrees C, the permissive temperature, induces viral DNA replication and virus production accompanied by late strand transcription. In two independently derived noninducible cell lines, L strand transcription is never observed, even after cultivation at the permissive temperature. A smaller fraction of the E strand is transcribed in each noninducible cell than in its inducible parent, and this difference is further characterized as a lack of transcripts of portions of HpaII restriction endonuclease fragments 2 and 6.", "contents": "Virus-secific transcription in 3T3 cells transformed by the ts-a mutant of polyoma virus. Virus-specific RNA transcription has been measured in 3T3 cells transformed by the ts-a mutant of polyoma virus by RNA-excess hybridization to the separated strands of polyoma DNA. In two cloned sublines maintained at 39 degrees C, the nonpermissive temperature for the A gene function, RNA transcripts of a large fraction of the \"early\" strand are detected in both nuclear and cytoplasmic RNA fractions, but no \"late\" strand transcription is detected. Temperature shift to 31.5 degrees C, the permissive temperature, induces viral DNA replication and virus production accompanied by late strand transcription. In two independently derived noninducible cell lines, L strand transcription is never observed, even after cultivation at the permissive temperature. A smaller fraction of the E strand is transcribed in each noninducible cell than in its inducible parent, and this difference is further characterized as a lack of transcripts of portions of HpaII restriction endonuclease fragments 2 and 6."}
{"id": "PMID:192917", "title": "Analysis of intracellular feline leukemia virus proteins II. Generation of feline leukemia virus structural proteins from precursor polypeptides.", "content": "The synthesis and processing of feline leukemia virus (FeLV) polypeptides were studied in a chronically infected feline thymus tumor cell line, F-422, which produces the Rickard strain of FeLV. Immune precipitation with antiserum to FeLV p30 and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used to isolate intracellular FeLV p30 and possible precursor polypeptides. SDS-PAGE of immune precipitates from cells pulse-labeled for 2.5 min with [35S]methionin revealed the presence of a 60,000-dalton precursor polypeptide (Pp60) as well as a 30,000-dalton polypeptide. When cells were grown in the presence of the proline analogue L-azetidine-2-carboxylic acid, a 70,000-dalton precursor polypeptide (Pp70) was found in addition to Pp60 after a 2.5-min pulse. The cleavage of Pp60 could be partially inhibited by the general protease inhibitor phenyl methyl sulfonyl fluoride (PMSF). This partial inhibition was found to occur only if PMSF was present during pulse-labeling. Intracellular Pp70 and Pp60 and FeLV virion p70, p30, p15, p11, and p10 were subjected to tryptic peptide analysis. The results of this tryptic peptide analysis demonstrated that intracellular Pp70 and virion p70 were identical and that both contained the tryptic peptides of FeLV p30, p15, p11, and p10. Pp60 contained the tryptic peptides of FeLV P30, P15, and P10, but lacked the tryptic peptides of P11. The results of pactamycin gene ordering experiments indicated that the small structural proteins of FeLV are ordered p11-p15-p10-p30. The data indicate that the small structural proteins of FeLV are synthesized as part of a 70,000-dalton precursor. A cleavage scheme for the generation of FeLV p70, p30, p15, p11, and p10 from precursor polypeptides is proposed.", "contents": "Analysis of intracellular feline leukemia virus proteins II. Generation of feline leukemia virus structural proteins from precursor polypeptides. The synthesis and processing of feline leukemia virus (FeLV) polypeptides were studied in a chronically infected feline thymus tumor cell line, F-422, which produces the Rickard strain of FeLV. Immune precipitation with antiserum to FeLV p30 and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were used to isolate intracellular FeLV p30 and possible precursor polypeptides. SDS-PAGE of immune precipitates from cells pulse-labeled for 2.5 min with [35S]methionin revealed the presence of a 60,000-dalton precursor polypeptide (Pp60) as well as a 30,000-dalton polypeptide. When cells were grown in the presence of the proline analogue L-azetidine-2-carboxylic acid, a 70,000-dalton precursor polypeptide (Pp70) was found in addition to Pp60 after a 2.5-min pulse. The cleavage of Pp60 could be partially inhibited by the general protease inhibitor phenyl methyl sulfonyl fluoride (PMSF). This partial inhibition was found to occur only if PMSF was present during pulse-labeling. Intracellular Pp70 and Pp60 and FeLV virion p70, p30, p15, p11, and p10 were subjected to tryptic peptide analysis. The results of this tryptic peptide analysis demonstrated that intracellular Pp70 and virion p70 were identical and that both contained the tryptic peptides of FeLV p30, p15, p11, and p10. Pp60 contained the tryptic peptides of FeLV P30, P15, and P10, but lacked the tryptic peptides of P11. The results of pactamycin gene ordering experiments indicated that the small structural proteins of FeLV are ordered p11-p15-p10-p30. The data indicate that the small structural proteins of FeLV are synthesized as part of a 70,000-dalton precursor. A cleavage scheme for the generation of FeLV p70, p30, p15, p11, and p10 from precursor polypeptides is proposed."}
{"id": "PMID:192918", "title": "Genetic studies of the ploidy of Moloney murine leukemia virus.", "content": "An assay for Moloney murine leukemia virus was developed that made use of the production of morphologically altered foci in nonproducer mouse cells (15F) carrying murine sarcoma virus. Wild-type (wt) virus gave a ratio of titers at 39 degrees C/34degrees C = 1.05 +/- 0.45 (standard deviation;n = 20). A spontaneous, thermosensitive (ts) mutant of Moloney murine leukemia virus, ts3, defective in a late viral function, gave 39 degrees C/34degrees C = 0. A murine cell line (TB) was mixedly infected with ts3 and wt (multiplicities of infection, 7.8:4.3), cloned after infection, and shown to be infected by both viruses. At 34 degrees C it produced wt, ts, and particles of mixed parentage. The heterozygotes (hz) had ratios of assays 39 degrees C/34 degrees C = 0.06 to 0.84 (mean, 0.36). To eliminate possible interference by multiploid particles with determination of the proportions of the three types of particles, the virus produced by the mixedly infected, cloned cell line at 34 degrees C was distributed by velocity sedimentation in a sucrose gradient, and virus was picked from the lightest part of the gradient. The proportions of ts, wt, and hz were 0.27, 0.26, and 0.47. Those particles identified as hz segreated ts, wt, and hz in the proportions 0.24, 0.27, and 0.49, respectively. These values were not significantly different from those predicted from a diploid model of the genome.", "contents": "Genetic studies of the ploidy of Moloney murine leukemia virus. An assay for Moloney murine leukemia virus was developed that made use of the production of morphologically altered foci in nonproducer mouse cells (15F) carrying murine sarcoma virus. Wild-type (wt) virus gave a ratio of titers at 39 degrees C/34degrees C = 1.05 +/- 0.45 (standard deviation;n = 20). A spontaneous, thermosensitive (ts) mutant of Moloney murine leukemia virus, ts3, defective in a late viral function, gave 39 degrees C/34degrees C = 0. A murine cell line (TB) was mixedly infected with ts3 and wt (multiplicities of infection, 7.8:4.3), cloned after infection, and shown to be infected by both viruses. At 34 degrees C it produced wt, ts, and particles of mixed parentage. The heterozygotes (hz) had ratios of assays 39 degrees C/34 degrees C = 0.06 to 0.84 (mean, 0.36). To eliminate possible interference by multiploid particles with determination of the proportions of the three types of particles, the virus produced by the mixedly infected, cloned cell line at 34 degrees C was distributed by velocity sedimentation in a sucrose gradient, and virus was picked from the lightest part of the gradient. The proportions of ts, wt, and hz were 0.27, 0.26, and 0.47. Those particles identified as hz segreated ts, wt, and hz in the proportions 0.24, 0.27, and 0.49, respectively. These values were not significantly different from those predicted from a diploid model of the genome."}
{"id": "PMID:192921", "title": "Isolated trigeminal neuropathy. An unusual complication of carcinoma of the lung.", "content": "The occurrence of isolated metastasis to the trigeminal nerve or ganglion form a distant, solid tumor is rare. This communication describes a patient with carcinoma of the lung; an isolated trigeminal neuropathy developed and at autopsy proved to be secondary to metastasis to the trigeminal ganglion. The appearance of a trigeminal neuropathy in a patient with an active solid tumor elsewhere in the body is most likely due to metastasis.", "contents": "Isolated trigeminal neuropathy. An unusual complication of carcinoma of the lung. The occurrence of isolated metastasis to the trigeminal nerve or ganglion form a distant, solid tumor is rare. This communication describes a patient with carcinoma of the lung; an isolated trigeminal neuropathy developed and at autopsy proved to be secondary to metastasis to the trigeminal ganglion. The appearance of a trigeminal neuropathy in a patient with an active solid tumor elsewhere in the body is most likely due to metastasis."}
{"id": "PMID:192922", "title": "Control of renin secretion.", "content": "The present study was designed to examine the interrelationship between the intrarenal vascular receptor and the sympathetic nerve, beta-adrenergic system, for renin secretion in the anesthetized dog. 1) A reduction in renal arterial pressure from a control pressure to 100 mmHg changed neither ther flow rates of all cortex zones nor renin secretion. Further reduction of renal arterial pressure to 75 mmHg resulted in a significant increase of renin secretion and a decrease of blood flow in the outer cortex. Intrarenal arterial infusion of norepinephrine at a control pressure increased a renin secretion. However, norepinephrine infusion at a reduced pressure suppressed the renin release with a recovery of the vascular resistance to the control level. These results suggest that the changes in the degree of blood flow and pressure in the renal afferent arterioles are not essential for the renin secretion,but renin secretion by the pressure reduction might be related to the autoregulatory capacity of afferent arterioles in the outer cortex. 2) At 5 min of hemorrhagic period (75 mmHg) arterial PRA elevated in control, and phenoxybenzamine and propranolol treated groups and any significant difference in responses was not observed among groups. However, at 60 min of hemorrhagic hypotensive period PRA in control and phenoxybenzamine treated groups further increased, but PRA in propranolol treated group was not alter from its 15 min value. These results indicated that the roles of vascular receptor and renal sympathetic nervous sytem in receptor and renal sympathetic nervous system in renin secretion might be separated, and that the renal sympathetic nervous system did not relate to the early response of renin release, but related to the late response. 3) Intrarenal arterial infusion of cAMP and DbcAMP resulted in a significant increase of renin release. In addition, CaC12 solution was infuesed into the renal artery and a significant rise in renal venous PRA was observed within 5 min of infusion. These data suggested that a beta-adrenergic receptor-adenyl cyclase-cAMP system was involved in the control of renin secretion, and that since the intracellular effect of cAMP was partly related to the change of intracellular Ca distribution, its change resulted in an increase in renin secretion.", "contents": "Control of renin secretion. The present study was designed to examine the interrelationship between the intrarenal vascular receptor and the sympathetic nerve, beta-adrenergic system, for renin secretion in the anesthetized dog. 1) A reduction in renal arterial pressure from a control pressure to 100 mmHg changed neither ther flow rates of all cortex zones nor renin secretion. Further reduction of renal arterial pressure to 75 mmHg resulted in a significant increase of renin secretion and a decrease of blood flow in the outer cortex. Intrarenal arterial infusion of norepinephrine at a control pressure increased a renin secretion. However, norepinephrine infusion at a reduced pressure suppressed the renin release with a recovery of the vascular resistance to the control level. These results suggest that the changes in the degree of blood flow and pressure in the renal afferent arterioles are not essential for the renin secretion,but renin secretion by the pressure reduction might be related to the autoregulatory capacity of afferent arterioles in the outer cortex. 2) At 5 min of hemorrhagic period (75 mmHg) arterial PRA elevated in control, and phenoxybenzamine and propranolol treated groups and any significant difference in responses was not observed among groups. However, at 60 min of hemorrhagic hypotensive period PRA in control and phenoxybenzamine treated groups further increased, but PRA in propranolol treated group was not alter from its 15 min value. These results indicated that the roles of vascular receptor and renal sympathetic nervous sytem in receptor and renal sympathetic nervous system in renin secretion might be separated, and that the renal sympathetic nervous system did not relate to the early response of renin release, but related to the late response. 3) Intrarenal arterial infusion of cAMP and DbcAMP resulted in a significant increase of renin release. In addition, CaC12 solution was infuesed into the renal artery and a significant rise in renal venous PRA was observed within 5 min of infusion. These data suggested that a beta-adrenergic receptor-adenyl cyclase-cAMP system was involved in the control of renin secretion, and that since the intracellular effect of cAMP was partly related to the change of intracellular Ca distribution, its change resulted in an increase in renin secretion."}
{"id": "PMID:192925", "title": "Viral growth in splenic megakaryocytes of mice experimentally infected with mouse hepatitis virus, MHV-2.", "content": "Electron microscopic and immunofluorescence studies were made on the spleen of mice infected intraperitoneally with mouse hepatitis virus, MHV-2. Virions and their budding process were demonstrable in reticulum cells as well as megakaryocytes at early stage of infection with a marked decrease in number of peripheral platelets, while histiocytes and macrophages were also found to have a large number of virions at later stage.", "contents": "Viral growth in splenic megakaryocytes of mice experimentally infected with mouse hepatitis virus, MHV-2. Electron microscopic and immunofluorescence studies were made on the spleen of mice infected intraperitoneally with mouse hepatitis virus, MHV-2. Virions and their budding process were demonstrable in reticulum cells as well as megakaryocytes at early stage of infection with a marked decrease in number of peripheral platelets, while histiocytes and macrophages were also found to have a large number of virions at later stage."}
{"id": "PMID:192926", "title": "Isolation and some properties of temperature-sensitive mutants of mouse fibroblasts with respect to morphological transformation.", "content": "We have isolated from a mouse fibroblast strain C3H2K several temperature-sensitive mutants that express their transformed phenotype at low (33 degress C) but not at high (38 degrees C) temperature. The mutant clones exhibited a piled up and criss-cross pattern of growth and a high saturation density at 33 degrees C, but flat density-inhibited monolayer and a low saturation density at 38 degrees C. The temperature-dependent exprestion of transformed phenotype was fully reversible upon temperature shift, and seemed to require cell division. Plating efficiencies of the clones in liquid medium were slightly higher at 33 degrees C than at 38 degrees C, but the cells were unable to form colonies in soft  agar medium.", "contents": "Isolation and some properties of temperature-sensitive mutants of mouse fibroblasts with respect to morphological transformation. We have isolated from a mouse fibroblast strain C3H2K several temperature-sensitive mutants that express their transformed phenotype at low (33 degress C) but not at high (38 degrees C) temperature. The mutant clones exhibited a piled up and criss-cross pattern of growth and a high saturation density at 33 degrees C, but flat density-inhibited monolayer and a low saturation density at 38 degrees C. The temperature-dependent exprestion of transformed phenotype was fully reversible upon temperature shift, and seemed to require cell division. Plating efficiencies of the clones in liquid medium were slightly higher at 33 degrees C than at 38 degrees C, but the cells were unable to form colonies in soft  agar medium."}
{"id": "PMID:192927", "title": "Nasoencephalopathy of mice infected intrananasally with a mouse hepatitis virus, JHM strain.", "content": "A mouse hepatitis virus, strain JHM, grown on DBT cell culture was inoculated intranasally into ICR-SLC weanling mice, and histopathological lesions were studied in relation to viral growth. In the spleen virus titer reached a peak of 10(3) PFU/0.2G 48 H after inoculation, and later it decreased gradually. No virus was detected from the liver throughout the experiment, while some early inflammatory reactions appeared in the spleen and liver without any further development. At 48 h postinoculation there existed degeneration and necrosis in the nasal mucosa and submocosa. In the brain and spinal cord active viral growth was seen at 48 h postinfection or later. In the olfactory bulb mitral cells were also affected with accumulation of glial cells and some meningitis. At 72 to 96 h postinoculation, degeneration of neurons and glial cells were remarkable in the tructus olfactorius, cortex of lobus piriformis, septa pellucidum and commissura anterior accompanying meningitis. At 120 h postinfection, pyramidal cells in the hippocumpus were also degenerated and necrotized, and nodular proliferation and collapse of glial cells, small foci of demyelination and perivascular cuffing were seen in the interbrain. At 144 h postinoculation or later, the lesions developed through the whole brain including the pons and medulla oblongata as well as spinal cord. Brain virus titers showed 10(5) PFU/0.2g at 120 h and 10(4) PFU/0.2g at 144 h postinfection. In mice surviving at 168 hr after inoculation severe demyelinating lesions were observed despite of a decreased virus titer. These findings suggest that intranasally inoculated virus might invade the olfactory bulb through the tractus olfactorius and then produce necrotizing lesions, extending later towards the posterior parts of the central nervous system.", "contents": "Nasoencephalopathy of mice infected intrananasally with a mouse hepatitis virus, JHM strain. A mouse hepatitis virus, strain JHM, grown on DBT cell culture was inoculated intranasally into ICR-SLC weanling mice, and histopathological lesions were studied in relation to viral growth. In the spleen virus titer reached a peak of 10(3) PFU/0.2G 48 H after inoculation, and later it decreased gradually. No virus was detected from the liver throughout the experiment, while some early inflammatory reactions appeared in the spleen and liver without any further development. At 48 h postinoculation there existed degeneration and necrosis in the nasal mucosa and submocosa. In the brain and spinal cord active viral growth was seen at 48 h postinfection or later. In the olfactory bulb mitral cells were also affected with accumulation of glial cells and some meningitis. At 72 to 96 h postinoculation, degeneration of neurons and glial cells were remarkable in the tructus olfactorius, cortex of lobus piriformis, septa pellucidum and commissura anterior accompanying meningitis. At 120 h postinfection, pyramidal cells in the hippocumpus were also degenerated and necrotized, and nodular proliferation and collapse of glial cells, small foci of demyelination and perivascular cuffing were seen in the interbrain. At 144 h postinoculation or later, the lesions developed through the whole brain including the pons and medulla oblongata as well as spinal cord. Brain virus titers showed 10(5) PFU/0.2g at 120 h and 10(4) PFU/0.2g at 144 h postinfection. In mice surviving at 168 hr after inoculation severe demyelinating lesions were observed despite of a decreased virus titer. These findings suggest that intranasally inoculated virus might invade the olfactory bulb through the tractus olfactorius and then produce necrotizing lesions, extending later towards the posterior parts of the central nervous system."}
{"id": "PMID:192928", "title": "Experimental double infection of Japanese encephalitis virus and herpes simplex virus in mouse brain.", "content": "In our laboratory, 64 autopsy cases of Japanese encephalitis patients were examined by immunofluorescence. Three patients showed some evidences of double infection of Japanese encephalitis virus and herpes simplex virus. Experiments were done to see the mechanisms of double infection. In doubly infected mice, Japanese encephalitis virus antigen was localized in the herpes simplex virus infected areas in the brain. These results suggested that \"blood brain barrier\" was broken by herpes simplex virus infection and Japanese encephalitis virus gained access to the susceptible cells.", "contents": "Experimental double infection of Japanese encephalitis virus and herpes simplex virus in mouse brain. In our laboratory, 64 autopsy cases of Japanese encephalitis patients were examined by immunofluorescence. Three patients showed some evidences of double infection of Japanese encephalitis virus and herpes simplex virus. Experiments were done to see the mechanisms of double infection. In doubly infected mice, Japanese encephalitis virus antigen was localized in the herpes simplex virus infected areas in the brain. These results suggested that \"blood brain barrier\" was broken by herpes simplex virus infection and Japanese encephalitis virus gained access to the susceptible cells."}
{"id": "PMID:192930", "title": "Production and properties of theta-toxin of Clostridium perfringens with special reference to lethal activity.", "content": "theta-Toxin of Clostridium perfringens produced in a synthetic medium showed high toxicity. The mouse was killed with 5-10 hemolytic units of the toxin. Neutralization experiments showed that lethal and hemolytic activities were due to the same toxic entity. The amount of theta-toxin expressed in lethal activity reached more than 30% that of alpha-toxin in the synthetic medium SM67. Although the activities of alpha-and theta-toxins were not additive in terms of LD50, increase in the ratio of theta-toxin to alpha-toxin resulted in reduction of the survival time of the mouse injected with a lethal dosis of the mixture of the two toxins when compared with alpha-toxin alone. Unlike those produced in other media, the hemolytic and lethal activities of theta-toxin produced in the synthetic medium was not activated by reduction with thioglycollate, even after partial purification. In other respects, the toxin was not different significantly from those reported in the past. The toxic form was detected also in complex medium. It was suggested that theta-toxin may be produced as a nascent entity.", "contents": "Production and properties of theta-toxin of Clostridium perfringens with special reference to lethal activity. theta-Toxin of Clostridium perfringens produced in a synthetic medium showed high toxicity. The mouse was killed with 5-10 hemolytic units of the toxin. Neutralization experiments showed that lethal and hemolytic activities were due to the same toxic entity. The amount of theta-toxin expressed in lethal activity reached more than 30% that of alpha-toxin in the synthetic medium SM67. Although the activities of alpha-and theta-toxins were not additive in terms of LD50, increase in the ratio of theta-toxin to alpha-toxin resulted in reduction of the survival time of the mouse injected with a lethal dosis of the mixture of the two toxins when compared with alpha-toxin alone. Unlike those produced in other media, the hemolytic and lethal activities of theta-toxin produced in the synthetic medium was not activated by reduction with thioglycollate, even after partial purification. In other respects, the toxin was not different significantly from those reported in the past. The toxic form was detected also in complex medium. It was suggested that theta-toxin may be produced as a nascent entity."}
{"id": "PMID:192931", "title": "Ascending spinal tracts of the spino-bulbo-spinal reflex in cats.", "content": "Twenty-six chloralosed cats were employed in order to determine spinal ascending pathways of the spino-bulbo-spinal (SBS) reflex evoked by stimulation of the sural nerve. 1. Partial spinal transection of the dorsal part of the lateral funiculus abolished the SBS reflex ipsilateral to sural nerve stimulation. 2. By recording spinal cord potentials in response to sural nerve stimulation two pathways were established in the dorsolateral funiculus as the spinal ascending tracts of the SBS reflex; one is the direct pathway to the bulbar reticular-formation (direct spino-reticular tract) and the other one (indirect spino-reticular tract) is the relayed by the lateral cervical nucleus. Direct stimulation of the dorsolateral funiculus at the lumbar level elicited the SBS reflex. 3. Short-latency unit discharges were recorded from axons of the direct spino-reticular tract by sural nerve stimulation. These axons were discharged antidromically by stimulation of the bulbar reticular formation. 4. Intracellular recordings from the neurons of the lateral cervical nucleus revealed that spike potentials, riding on EPSPs, were induced by sural nerve stimulation and antidromic firings were obtained by stimulation of the bulbar reticular formation. 5. Neurons originating the spino-reticular tract, direct and indirect, were located in the Rexed V-VII laminae in the lower lumbar segments. They were fired monosynaptically by sural nerve stimulation and antidromically by stimulating the dorsolateral funiculus of the lumbar segments. Among them, some were activated antidromically by stimulating the bulbar reticular formation.", "contents": "Ascending spinal tracts of the spino-bulbo-spinal reflex in cats. Twenty-six chloralosed cats were employed in order to determine spinal ascending pathways of the spino-bulbo-spinal (SBS) reflex evoked by stimulation of the sural nerve. 1. Partial spinal transection of the dorsal part of the lateral funiculus abolished the SBS reflex ipsilateral to sural nerve stimulation. 2. By recording spinal cord potentials in response to sural nerve stimulation two pathways were established in the dorsolateral funiculus as the spinal ascending tracts of the SBS reflex; one is the direct pathway to the bulbar reticular-formation (direct spino-reticular tract) and the other one (indirect spino-reticular tract) is the relayed by the lateral cervical nucleus. Direct stimulation of the dorsolateral funiculus at the lumbar level elicited the SBS reflex. 3. Short-latency unit discharges were recorded from axons of the direct spino-reticular tract by sural nerve stimulation. These axons were discharged antidromically by stimulation of the bulbar reticular formation. 4. Intracellular recordings from the neurons of the lateral cervical nucleus revealed that spike potentials, riding on EPSPs, were induced by sural nerve stimulation and antidromic firings were obtained by stimulation of the bulbar reticular formation. 5. Neurons originating the spino-reticular tract, direct and indirect, were located in the Rexed V-VII laminae in the lower lumbar segments. They were fired monosynaptically by sural nerve stimulation and antidromically by stimulating the dorsolateral funiculus of the lumbar segments. Among them, some were activated antidromically by stimulating the bulbar reticular formation."}
{"id": "PMID:192936", "title": "[Relationship between the kininase- and angiotensin- converting activity under normal conditions and in experimental myocardial infarct].", "content": "In rat experiments the depressor and pressor responses to kinins and angiotensins recorded in the carotid artery were compared as to the different methods of their administration. With intravenous injection, the responses to bradykinin and kallidin were lower, and to angiotensin I--higher, than with their intra-aortic administration. The responses to angiotensin II remain identical under these conditions. The administration of all the preparations against the background of 2,3-dimercaptopropanol (unithiol) resulted in levelling of the responses irrespective of the mode of administration. In experimental myocardial infarction induced in rats by ligation of the coronary artery a reduction of the kinin-destructing and an increase of the angiotensin-converting activity was noted in the early postinfarction period. The response of the peripheral vessels to angiotensin, bradykinin and noradrenaline is decreased, while that to isoproterenol remain unchanged. The obtained results support the concept of the existence of the kininase and angiotensin-converting activity connected with a common biochemical factor of pulmonary circulation. Changes in the proportion of these functions under normal conditions and in cases of pathological states are interpreted as a particular regulation mechanism of the vascular tone and arterial pressure.", "contents": "[Relationship between the kininase- and angiotensin- converting activity under normal conditions and in experimental myocardial infarct]. In rat experiments the depressor and pressor responses to kinins and angiotensins recorded in the carotid artery were compared as to the different methods of their administration. With intravenous injection, the responses to bradykinin and kallidin were lower, and to angiotensin I--higher, than with their intra-aortic administration. The responses to angiotensin II remain identical under these conditions. The administration of all the preparations against the background of 2,3-dimercaptopropanol (unithiol) resulted in levelling of the responses irrespective of the mode of administration. In experimental myocardial infarction induced in rats by ligation of the coronary artery a reduction of the kinin-destructing and an increase of the angiotensin-converting activity was noted in the early postinfarction period. The response of the peripheral vessels to angiotensin, bradykinin and noradrenaline is decreased, while that to isoproterenol remain unchanged. The obtained results support the concept of the existence of the kininase and angiotensin-converting activity connected with a common biochemical factor of pulmonary circulation. Changes in the proportion of these functions under normal conditions and in cases of pathological states are interpreted as a particular regulation mechanism of the vascular tone and arterial pressure."}
{"id": "PMID:192938", "title": "[Chiasmatic syndromes-diagnostic possibilities with computerized tomography (CT)].", "content": "The normal suprasellar subarachnoid space (so-called \"suprasellar hexagon\") and its content are fairly well demonstrated by CT. Abnormal appearance (obstruction, stenosis, asymmetry) of this space is always suspect of a suprasellar space occupying lesion. Enhancing (intravenous application of iodine containing contrast medium) helps to delineate the exact tumor extension. The point of origin--important for deciding on the nature of a lesion--is often difficult to determine. The CT-pattern itself is not specific for a certain kind of tumor. We have observed a typical chiasmatic syndrome with all meningiomas of the tuberculum sellae, with 75% of the chromophobe adenomas and with 50% of the craniopharyngiomas. Absence of this syndrome was due to high position of the tumor (craniopharyngiomas) or to parasellar extension of the lesion (chromophobe adenomas). Diagnosis of recurrent tumor is difficult; it must be based on the post-operative CT-examination. Chiasmatic syndromes not due to the pressure effect of a space occupying lesion (i.e. chiasmatic syndromes of vascular, toxic or degenerative origin) can not be assessed directly by CT.", "contents": "[Chiasmatic syndromes-diagnostic possibilities with computerized tomography (CT)]. The normal suprasellar subarachnoid space (so-called \"suprasellar hexagon\") and its content are fairly well demonstrated by CT. Abnormal appearance (obstruction, stenosis, asymmetry) of this space is always suspect of a suprasellar space occupying lesion. Enhancing (intravenous application of iodine containing contrast medium) helps to delineate the exact tumor extension. The point of origin--important for deciding on the nature of a lesion--is often difficult to determine. The CT-pattern itself is not specific for a certain kind of tumor. We have observed a typical chiasmatic syndrome with all meningiomas of the tuberculum sellae, with 75% of the chromophobe adenomas and with 50% of the craniopharyngiomas. Absence of this syndrome was due to high position of the tumor (craniopharyngiomas) or to parasellar extension of the lesion (chromophobe adenomas). Diagnosis of recurrent tumor is difficult; it must be based on the post-operative CT-examination. Chiasmatic syndromes not due to the pressure effect of a space occupying lesion (i.e. chiasmatic syndromes of vascular, toxic or degenerative origin) can not be assessed directly by CT."}
{"id": "PMID:192939", "title": "[Endocrinology of the chiasma syndromes (author's transl)].", "content": "A wealth of new knowledge about the function of the hypothalamo-hypophyseal system has been accumulated over the past ten years and progress keeps going at a fast pace. Several factors have contributed to this explosive growth: Pituitary hormones can now be measured by radio-immunoassay in body fluids, hypothalamic stimulating and inhibiting factors have been identified and are available for clinical studies and dynamic tests have been developed for detailed investigations of minor disturbances in the pituitary control system. A tremendous gain in accuracy of clinical diagnosis and endocrine follow-up is one of the consequences. Furthermore, new clinical pictures have emerged such as several variants of the hyperprolactinemia-hypogonadism syndrome or the concept of pituitary microadenoma. At the same time, neuropharmacology is also developing at a tremendous pace and exceedingly interesting perspectives linking neurotransmission with endocrinology and with various diseases of the brain are emerging. One highlight is the discovery of bromoergocryptine as a dopaminergic agonist, active in suppressing prolactin secretion as well as in treating Parkinsonism. In a second part of this presentation 5 cases with pituitary disease are presented. They were selected to cover part of the wide range of clinical signs and symptoms produced by tumours of the pituitary region. There is indeed no good relationship between ophthalmo-neurologic symptoms, destruction of the bony sella and endocrine disturbances.", "contents": "[Endocrinology of the chiasma syndromes (author's transl)]. A wealth of new knowledge about the function of the hypothalamo-hypophyseal system has been accumulated over the past ten years and progress keeps going at a fast pace. Several factors have contributed to this explosive growth: Pituitary hormones can now be measured by radio-immunoassay in body fluids, hypothalamic stimulating and inhibiting factors have been identified and are available for clinical studies and dynamic tests have been developed for detailed investigations of minor disturbances in the pituitary control system. A tremendous gain in accuracy of clinical diagnosis and endocrine follow-up is one of the consequences. Furthermore, new clinical pictures have emerged such as several variants of the hyperprolactinemia-hypogonadism syndrome or the concept of pituitary microadenoma. At the same time, neuropharmacology is also developing at a tremendous pace and exceedingly interesting perspectives linking neurotransmission with endocrinology and with various diseases of the brain are emerging. One highlight is the discovery of bromoergocryptine as a dopaminergic agonist, active in suppressing prolactin secretion as well as in treating Parkinsonism. In a second part of this presentation 5 cases with pituitary disease are presented. They were selected to cover part of the wide range of clinical signs and symptoms produced by tumours of the pituitary region. There is indeed no good relationship between ophthalmo-neurologic symptoms, destruction of the bony sella and endocrine disturbances."}
{"id": "PMID:192940", "title": "[Functional histopathology of pituitary neoplasms (author's transl)].", "content": "The generally accepted classification of pituitary adenomas into eosinophilic, basophilic, mixed, and chromophobe types has not been very useful since no clear correlation exists between the staining character of the tumor cells and the clinical syndrome produced. The ultrastructural examination of different adenoma types with clinically manifest endocrine activity (acromegaly, amenorrhea-galactorrhea-syndrome, Cushing's disease) shows that the type of hormone secreted can only be determined in few cases. The ultrastructure is more representative of the activity of the secretory process than of the type of the product. Histoimmunological methods achieve the specific identification of the various types of adenomas with endocrine symptomatology. The so-called \"chromophobe\" adenomas, which only manifest signs of a space occupying lesion with pituitary insufficiency of varying degree and compression of the visual pathways, represent a mixed group. The majority of the cases (about 60%) shows increased prolactin secretion with amenorrhea or loss of potency, but without galactorrhea or gynecomastia. A small group of cases may either produce normal hormones (growth hormone or prolactin) at a very low rate, or secrete hormone fragments or abnormal, as yet undeterminable substances. The oncocytomas, which stain with eosin in light microscopy, seem to suffer from a defective metabolism and therefore may have lost the ability of hormone production.", "contents": "[Functional histopathology of pituitary neoplasms (author's transl)]. The generally accepted classification of pituitary adenomas into eosinophilic, basophilic, mixed, and chromophobe types has not been very useful since no clear correlation exists between the staining character of the tumor cells and the clinical syndrome produced. The ultrastructural examination of different adenoma types with clinically manifest endocrine activity (acromegaly, amenorrhea-galactorrhea-syndrome, Cushing's disease) shows that the type of hormone secreted can only be determined in few cases. The ultrastructure is more representative of the activity of the secretory process than of the type of the product. Histoimmunological methods achieve the specific identification of the various types of adenomas with endocrine symptomatology. The so-called \"chromophobe\" adenomas, which only manifest signs of a space occupying lesion with pituitary insufficiency of varying degree and compression of the visual pathways, represent a mixed group. The majority of the cases (about 60%) shows increased prolactin secretion with amenorrhea or loss of potency, but without galactorrhea or gynecomastia. A small group of cases may either produce normal hormones (growth hormone or prolactin) at a very low rate, or secrete hormone fragments or abnormal, as yet undeterminable substances. The oncocytomas, which stain with eosin in light microscopy, seem to suffer from a defective metabolism and therefore may have lost the ability of hormone production."}
{"id": "PMID:192942", "title": "Adverse effects of mouse hepatitis virus on ascites myeloma passage in the BALB/eJ mouse.", "content": "During experimental serial passage of ascites myelomas through BALB/cJ mice, unexpected illness and premature deaths occurred. Postmortem examination of affected mice revealed focal or diffuse discolored depressed areas in the liver and, in some cases, splenomegaly. Histopathologic findings consisted of focal to diffuse areas of necrosis with minimal leukocytic infiltration. Aerobic and anaerobic bacterial cultures of livers and spleens from affected mice were negative. Mouse hepatitis virus (MHV) was isolated from livers of clinically ill mice and from the ascites myeloma lines. An MHV contaminated ascites myeloma line, when passed into nude (nu/nu) mice, killed the animals in 6 days; the virus was isolated from livers of inoculated mice. Attempts to determine the source of the infection were unsuccessful. Serologic survey of newly acquired mice indicated no evidence of antibodies to MHV while mice in holding rooms had titers that ranged from 1:10 to 1:40. Two solid myeloma lines (being maintained by subcutaneous passage) were negative for MHV when tested by virus isolation techniques, and nine lines were negative to 11 murine viruses when tested by mouse antibody production assay. Attempts to demonstrate Eperythrozoon coccoides in control BALB/cJ mice were unsuccessful. Because of the outbreak, changes were made in animal handling procedures. A colony of BALB/cAn mice negative to MHV antibodies was established to provide animals for experimental passage of tumors, and animals in both the breeding and transfer room were placed under filter tops. The results were encouraging. In the four newly established tumor lines, one having been passed 46 times, no illness or unexplained deaths were observed.", "contents": "Adverse effects of mouse hepatitis virus on ascites myeloma passage in the BALB/eJ mouse. During experimental serial passage of ascites myelomas through BALB/cJ mice, unexpected illness and premature deaths occurred. Postmortem examination of affected mice revealed focal or diffuse discolored depressed areas in the liver and, in some cases, splenomegaly. Histopathologic findings consisted of focal to diffuse areas of necrosis with minimal leukocytic infiltration. Aerobic and anaerobic bacterial cultures of livers and spleens from affected mice were negative. Mouse hepatitis virus (MHV) was isolated from livers of clinically ill mice and from the ascites myeloma lines. An MHV contaminated ascites myeloma line, when passed into nude (nu/nu) mice, killed the animals in 6 days; the virus was isolated from livers of inoculated mice. Attempts to determine the source of the infection were unsuccessful. Serologic survey of newly acquired mice indicated no evidence of antibodies to MHV while mice in holding rooms had titers that ranged from 1:10 to 1:40. Two solid myeloma lines (being maintained by subcutaneous passage) were negative for MHV when tested by virus isolation techniques, and nine lines were negative to 11 murine viruses when tested by mouse antibody production assay. Attempts to demonstrate Eperythrozoon coccoides in control BALB/cJ mice were unsuccessful. Because of the outbreak, changes were made in animal handling procedures. A colony of BALB/cAn mice negative to MHV antibodies was established to provide animals for experimental passage of tumors, and animals in both the breeding and transfer room were placed under filter tops. The results were encouraging. In the four newly established tumor lines, one having been passed 46 times, no illness or unexplained deaths were observed."}
{"id": "PMID:192952", "title": "Radiological evidence of lymphatic drainage of bone marrow cavity in long bones.", "content": "Injection of Lipiodol UF into the distal epiphyses of tibia and femur in the dog was followed within several minutes by visualization of lymphatics draining the bone. Some of the radioopaque material was retained in the bone marrow cavity and tiny lymph vessels originating in that area could be seen.  Contrast medium filled also the popliteal lymph node. The problem of migration of bone marrow lymphocytes through the lymphatics to the regional lymph nodes is discussed.", "contents": "Radiological evidence of lymphatic drainage of bone marrow cavity in long bones. Injection of Lipiodol UF into the distal epiphyses of tibia and femur in the dog was followed within several minutes by visualization of lymphatics draining the bone. Some of the radioopaque material was retained in the bone marrow cavity and tiny lymph vessels originating in that area could be seen.  Contrast medium filled also the popliteal lymph node. The problem of migration of bone marrow lymphocytes through the lymphatics to the regional lymph nodes is discussed."}
{"id": "PMID:192954", "title": "The role of the adrenal cortex in human essential hypertension: keynote address.", "content": "The data presented establish that in early or mild essential hypertension there is a state of inappropriate hypermineralocorticoid activity represented by the sum of aldosterone and 18-hydroxy-11-deoxycorticosterone concentrations in the plasma. This disturbance, associated with a \"normal\" or excessive salt intake, would produce the arteriolar cationic changes in sodium, potassium, calcium, or magnesium leading to hypersensitivity or hyperresponsiveness of the arteriolar actomyosin to normal levels of circulating norepinephrine or angiotensin. The nature of the cationic changes in the arteriolar cells responsible for the increased tonicity of the arteriolar actomyosin, which is the fundamental cause of essential hypertension, remains to be elucidated.", "contents": "The role of the adrenal cortex in human essential hypertension: keynote address. The data presented establish that in early or mild essential hypertension there is a state of inappropriate hypermineralocorticoid activity represented by the sum of aldosterone and 18-hydroxy-11-deoxycorticosterone concentrations in the plasma. This disturbance, associated with a \"normal\" or excessive salt intake, would produce the arteriolar cationic changes in sodium, potassium, calcium, or magnesium leading to hypersensitivity or hyperresponsiveness of the arteriolar actomyosin to normal levels of circulating norepinephrine or angiotensin. The nature of the cationic changes in the arteriolar cells responsible for the increased tonicity of the arteriolar actomyosin, which is the fundamental cause of essential hypertension, remains to be elucidated."}
{"id": "PMID:192953", "title": "Hypothesis about the mechanism of protein folding.", "content": "A three-step mechanism of protein folding, proposed in our previous paper, is applied here to postulate the nature of the intermediates in the folding of rubredoxin, ferricytochrome c, and lysozyme. Contact maps are calculated for these three proteins, and it is shown that they contain much information (such as the polarity of residues in contact regions) about the structure of the native protein. Elementary processes are described for the formation of contact regions. Based on these concepts, details of the pathways of folding these three proteins from the unfolded to the native structure are postulated, focusing on the formation of ordered backbone structures (such as alpha-helical, extended, and chain-reversal conformations) in step A of the three-step mechanism and on the formation of contact regions in response to medium-and long-range interactions in steps B and C. It was found that chain reversals can often play an important role in forming contact regions in step A (short-range interactions) and in step B (medium-range interactions) but not in step C.", "contents": "Hypothesis about the mechanism of protein folding. A three-step mechanism of protein folding, proposed in our previous paper, is applied here to postulate the nature of the intermediates in the folding of rubredoxin, ferricytochrome c, and lysozyme. Contact maps are calculated for these three proteins, and it is shown that they contain much information (such as the polarity of residues in contact regions) about the structure of the native protein. Elementary processes are described for the formation of contact regions. Based on these concepts, details of the pathways of folding these three proteins from the unfolded to the native structure are postulated, focusing on the formation of ordered backbone structures (such as alpha-helical, extended, and chain-reversal conformations) in step A of the three-step mechanism and on the formation of contact regions in response to medium-and long-range interactions in steps B and C. It was found that chain reversals can often play an important role in forming contact regions in step A (short-range interactions) and in step B (medium-range interactions) but not in step C."}
{"id": "PMID:192973", "title": "Use of the telephone for short-term follow-up.", "content": "We have instituted a telephone appointment system (TAS) to follow patients with well-defined relatively minor problems. The patient is asked to call a special phone number at a specified date and time to obtain test results or information. A senior physician reviews each chart beforehand and indicates in lay terms, the information to be given to the patient by the clerk. Initial contact was made with 235 (58%) of the 404 scheduled telephone appointments reviewed during a four-week period. Physician data review time averaged one minute per chart and two full-time clerks were required. Although no improvement in patient compliance was found, significant savings of patient, physician, and nursing time are obvious. Additional advantages include decreased total patient load and the opportunity for senior physicians to assess the quality of care and provide feedback to the emergency department house officers.", "contents": "Use of the telephone for short-term follow-up. We have instituted a telephone appointment system (TAS) to follow patients with well-defined relatively minor problems. The patient is asked to call a special phone number at a specified date and time to obtain test results or information. A senior physician reviews each chart beforehand and indicates in lay terms, the information to be given to the patient by the clerk. Initial contact was made with 235 (58%) of the 404 scheduled telephone appointments reviewed during a four-week period. Physician data review time averaged one minute per chart and two full-time clerks were required. Although no improvement in patient compliance was found, significant savings of patient, physician, and nursing time are obvious. Additional advantages include decreased total patient load and the opportunity for senior physicians to assess the quality of care and provide feedback to the emergency department house officers."}
{"id": "PMID:192983", "title": "Metabolism of cholesteryl esters of very low density lipoproteins in the guinea pig.", "content": "Very low density lipoproteins from guinea pig plasma, endogenously labeled with 3H in both the esterified and free cholesterol moieties, were obtained from serum collected 20 hr after the intravenous injection of 3H-cholesterol into donor animals. When these lipoproteins were injected into recipient guinea pigs, the esterified 3H-cholesterol was rapidly cleared from the plasma; 24% was in the liver in 5 min and 54% in 15 min. A smaller fraction of the esterified cholesterol appeared in other plasma lipoprotein fractions, with 3H in the low density lipoproteins reaching a peak of 9%-18% of the injected esterified 3H-cholesterol between 30 and 60 min after the injection. The results indicate that most of the esterified cholesterol in very low density lipoproteins of guinea pig plasma is removed directly by the liver and a minor fraction is transferred to low density lipoproteins. The pattern of labeling of cholesteryl esters of high density lipoproteins in these experiments suggests that their low concentration in the guinea pig is accompanied by a rapid turnover rate.", "contents": "Metabolism of cholesteryl esters of very low density lipoproteins in the guinea pig. Very low density lipoproteins from guinea pig plasma, endogenously labeled with 3H in both the esterified and free cholesterol moieties, were obtained from serum collected 20 hr after the intravenous injection of 3H-cholesterol into donor animals. When these lipoproteins were injected into recipient guinea pigs, the esterified 3H-cholesterol was rapidly cleared from the plasma; 24% was in the liver in 5 min and 54% in 15 min. A smaller fraction of the esterified cholesterol appeared in other plasma lipoprotein fractions, with 3H in the low density lipoproteins reaching a peak of 9%-18% of the injected esterified 3H-cholesterol between 30 and 60 min after the injection. The results indicate that most of the esterified cholesterol in very low density lipoproteins of guinea pig plasma is removed directly by the liver and a minor fraction is transferred to low density lipoproteins. The pattern of labeling of cholesteryl esters of high density lipoproteins in these experiments suggests that their low concentration in the guinea pig is accompanied by a rapid turnover rate."}
{"id": "PMID:192984", "title": "Studies on the minimum reproducible unit of staphylococcal L-forms.", "content": "The minimum size of a reproducible unit of staphylococcal L-forms was determined by filtration and electron microscopic methods. Ultrathin sections of an induced strain of Staphylococcal L-forms (STA-EMT-1) in liquid medium revealed several types of structures, all of which were bound by a single membrane and most of which possessed ribosome-like granules. Many of the small granules were less than 0.3 micron and were attached to the membrane of the large bodies. Using a serial filtration method, it was observed that viable L-forms were still detected in 0.22 micron filtrate, but the viable cell count of L-forms decreased in number with the decrease in pore size of membrane filters. A fractionation technique, using L-forms filtered through a membrane filter with a 0.45 micron pore size, revealed that there were three classes of small bodies but only the first class with ribosome-like granules over approximately 0.2 micron in diameter seems to be able to reproduce.", "contents": "Studies on the minimum reproducible unit of staphylococcal L-forms. The minimum size of a reproducible unit of staphylococcal L-forms was determined by filtration and electron microscopic methods. Ultrathin sections of an induced strain of Staphylococcal L-forms (STA-EMT-1) in liquid medium revealed several types of structures, all of which were bound by a single membrane and most of which possessed ribosome-like granules. Many of the small granules were less than 0.3 micron and were attached to the membrane of the large bodies. Using a serial filtration method, it was observed that viable L-forms were still detected in 0.22 micron filtrate, but the viable cell count of L-forms decreased in number with the decrease in pore size of membrane filters. A fractionation technique, using L-forms filtered through a membrane filter with a 0.45 micron pore size, revealed that there were three classes of small bodies but only the first class with ribosome-like granules over approximately 0.2 micron in diameter seems to be able to reproduce."}
{"id": "PMID:192986", "title": "Screening for breast cancer by mammography: an Australian experience.", "content": "Four years' experience of screening well women for breast cancer by mammography is described. Twenty-six cancers were detected in 11,927 women (2-2 per 1,000), of which 20 were unsuspected by the patient and 12 were impalpable. Of the 26 cancers detected, 18 had no histological evidence of tumour in axillary lymph nodes, and 10 were impalpable and had unaffected axillary nodes. Four patients whose mammograms did not suggest malignant disease were subsequently found to have cancer, within 12 months.", "contents": "Screening for breast cancer by mammography: an Australian experience. Four years' experience of screening well women for breast cancer by mammography is described. Twenty-six cancers were detected in 11,927 women (2-2 per 1,000), of which 20 were unsuspected by the patient and 12 were impalpable. Of the 26 cancers detected, 18 had no histological evidence of tumour in axillary lymph nodes, and 10 were impalpable and had unaffected axillary nodes. Four patients whose mammograms did not suggest malignant disease were subsequently found to have cancer, within 12 months."}
{"id": "PMID:192985", "title": "Viral infections of the autonomic nervous system and its target organs: pathogenetic mechanisms.", "content": "The possibility that viruses can infect the peripheral autonomic nervous system (ANS) and cause a variety of acute, chronic or recurrent diseases, including such disorders as peptic ulcer, is proposed. By altering the functional activity of autonomic neurons or by seeding the target organs of these neurons with virus, infection of the ANS may produce a broad spectrum of clinical manifestations. Whether these manifestations are anatomically circumscribed or widespread will depend upon the route by which autonomic infection is acquired as well as the character of interaction between the virus and the infected autonomic neuron. In addition, it is proposed that autonomic ganglia may serve as reservoirs of latent viruses, insuring their preservation and intermittent transmission in the human community.", "contents": "Viral infections of the autonomic nervous system and its target organs: pathogenetic mechanisms. The possibility that viruses can infect the peripheral autonomic nervous system (ANS) and cause a variety of acute, chronic or recurrent diseases, including such disorders as peptic ulcer, is proposed. By altering the functional activity of autonomic neurons or by seeding the target organs of these neurons with virus, infection of the ANS may produce a broad spectrum of clinical manifestations. Whether these manifestations are anatomically circumscribed or widespread will depend upon the route by which autonomic infection is acquired as well as the character of interaction between the virus and the infected autonomic neuron. In addition, it is proposed that autonomic ganglia may serve as reservoirs of latent viruses, insuring their preservation and intermittent transmission in the human community."}
{"id": "PMID:192994", "title": "Detection of [3H]cyclic AMP in the transcription complex of rat liver mitochondria.", "content": "By equilibrium ultracentrifugation and electrophoresis in agarose gel data were obtained on the binding of [3H]cyclic adenosine monophosphate ([3H]cAMP) to the transcriptional complex of mitochondria with the density 1.825 g/ml in CsCl ethydium bromide. Treatment of the complex with RNase, DNase and pronase change the density of [3H]cAMP bound material; rifampicin prevents detection of [3H]cAMP. Study of inner membrane lysates showed that [3H]cAMP is bound to structures active in RNA and protein synthesis in mitochondria. The conclusion is made that cAMP is involved in formation of the transcriptional complex much as it is involved in initiation of transcription in bacterial operons.", "contents": "Detection of [3H]cyclic AMP in the transcription complex of rat liver mitochondria. By equilibrium ultracentrifugation and electrophoresis in agarose gel data were obtained on the binding of [3H]cyclic adenosine monophosphate ([3H]cAMP) to the transcriptional complex of mitochondria with the density 1.825 g/ml in CsCl ethydium bromide. Treatment of the complex with RNase, DNase and pronase change the density of [3H]cAMP bound material; rifampicin prevents detection of [3H]cAMP. Study of inner membrane lysates showed that [3H]cAMP is bound to structures active in RNA and protein synthesis in mitochondria. The conclusion is made that cAMP is involved in formation of the transcriptional complex much as it is involved in initiation of transcription in bacterial operons."}
{"id": "PMID:192995", "title": "Studies on the synthesis and structure of mitochondrial DNA in cells infected by Rous sarcoma viruses and on the occurrence of intramitochondrial virus-like particles in certain RSV-induced tumor cells.", "content": "1. The synthesis of mitochondrial DNA in CEF in vivo at 3,4 and 6 days after infection with RSV (Schmidt-Ruppin, subgroup A) was progressively stimulated 2 to 4-fold as compared with that in uninfected CEF cells grown in parallel. 2. The stimulation of mtDNA synthesis in vivo upon transformation was found to be temperature dependent when the thermosensitive mutant of RSV, T5, was used to infect the cells. 3. In contrast to mtDNA synthesis, nuclear DNA synthesis did not differ in transformed and uninfected cells, nor did it change significantly upon temperature shifts. 4. MtDNA (monomeric and catenated dimeric forms) in transformed and uninfected CEF replicate by displacement synthesis. Various replication intermediates are described. 5. The restriction endonuclease EcoRI cleaves closed circular mtDNA from CEF at one specific site. 6. Heteroduplex molecules formed between nicked circular and/or EcoRI cleaved mt DNA molecules from uninfected and transformed CEF revealed, with a few exceptions, no detectable base sequence heterogeneity in at least 98% of cases. 7. Intramitochondrial virus like particles (IMV) are described in hamster tumor cells. The evidence suggests both engulfment of cytoplasmic particles by mitochondria and the presence of intramitochondrial incomplete forms of particles. Bromodeoxyuridine was found to enhance the frequency of IMV.", "contents": "Studies on the synthesis and structure of mitochondrial DNA in cells infected by Rous sarcoma viruses and on the occurrence of intramitochondrial virus-like particles in certain RSV-induced tumor cells. 1. The synthesis of mitochondrial DNA in CEF in vivo at 3,4 and 6 days after infection with RSV (Schmidt-Ruppin, subgroup A) was progressively stimulated 2 to 4-fold as compared with that in uninfected CEF cells grown in parallel. 2. The stimulation of mtDNA synthesis in vivo upon transformation was found to be temperature dependent when the thermosensitive mutant of RSV, T5, was used to infect the cells. 3. In contrast to mtDNA synthesis, nuclear DNA synthesis did not differ in transformed and uninfected cells, nor did it change significantly upon temperature shifts. 4. MtDNA (monomeric and catenated dimeric forms) in transformed and uninfected CEF replicate by displacement synthesis. Various replication intermediates are described. 5. The restriction endonuclease EcoRI cleaves closed circular mtDNA from CEF at one specific site. 6. Heteroduplex molecules formed between nicked circular and/or EcoRI cleaved mt DNA molecules from uninfected and transformed CEF revealed, with a few exceptions, no detectable base sequence heterogeneity in at least 98% of cases. 7. Intramitochondrial virus like particles (IMV) are described in hamster tumor cells. The evidence suggests both engulfment of cytoplasmic particles by mitochondria and the presence of intramitochondrial incomplete forms of particles. Bromodeoxyuridine was found to enhance the frequency of IMV."}
{"id": "PMID:192996", "title": "Biosynthesis of subviral oncogenic particles (virosomes) in mitochondria of Rous sarcoma and Rauscher murine leukemia cells.", "content": "Experimental evidence for the presence and biosynthesis of subviral, leukemogenic particles in the isolated mitochondria of spleen cells of mice infected with Rauscher murine leukemia (RML) virus is presented. These subviral particles sediment at a density of 1.27-1.29 g/ml and induce splenomegaly and RML three weeks after i.v. or i.p. administration to white mice. Virosomes have been labelled with [32P]phosphate in the isolated mitochondria from RML spleen cells and high molecular weight (70S) [32P]RNA has been isolated from these subviral, leukemogenic particles. Rauscher virus group specific antigens were detected by immunodiffusion in the inner membrane and matrix fraction of the mitochondria of RML spleen cells. These results together with our earlier findings strongly suggest that mitochondria of the transformed cells participate in the biosynthesis of RNA tumor viruses. Possible mechanism of the penetration of viral genetic information of RNA tumor viruses into mitochondria of tumor cells in vivo is discussed.", "contents": "Biosynthesis of subviral oncogenic particles (virosomes) in mitochondria of Rous sarcoma and Rauscher murine leukemia cells. Experimental evidence for the presence and biosynthesis of subviral, leukemogenic particles in the isolated mitochondria of spleen cells of mice infected with Rauscher murine leukemia (RML) virus is presented. These subviral particles sediment at a density of 1.27-1.29 g/ml and induce splenomegaly and RML three weeks after i.v. or i.p. administration to white mice. Virosomes have been labelled with [32P]phosphate in the isolated mitochondria from RML spleen cells and high molecular weight (70S) [32P]RNA has been isolated from these subviral, leukemogenic particles. Rauscher virus group specific antigens were detected by immunodiffusion in the inner membrane and matrix fraction of the mitochondria of RML spleen cells. These results together with our earlier findings strongly suggest that mitochondria of the transformed cells participate in the biosynthesis of RNA tumor viruses. Possible mechanism of the penetration of viral genetic information of RNA tumor viruses into mitochondria of tumor cells in vivo is discussed."}
{"id": "PMID:192997", "title": "Integration and regulation of mitochondrial assembly in yeast.", "content": "The interactions between the mitochondrial and nucleocytoplasmic systems required for mitochondriogenesis have been investigated at several different levels. Those involved in the formation of functional enzyme complexes have been studied using cytochrome oxidase: this multimeric (2 X 7 and 2 X 6 subunits for enzymes from yeast and beef heart respectively) has been resolved, and the mitochondrial contribution has been shown to be dispensible for catalytic function proper. Using novel mutants, with a mitochondrial mode of inheritance, a mitochondrial gene product localized in the oligomycin-sensitive ATPase has been implicated in the assembly not only of this complex, but of cytochrome oxidase as well. Interactions required for the genetic competence of the mitochondrial system have become apparent as a result of studies in the mechanism of action of the highly effective mitochondrial mutagen ethidium bromide. This agent first becomes covalently inserted into mitochondrial DNA and, after its excision, eventually results in extensive degradation of the macromolecule. The excision reaction has now been shown to be performed by a complex between the oligomycin-sensitive ATPase and a DNA-binding protein presumably involved in recognizing the damage. On the level of replication and expression of the mitochondrial genome studies using thermolabile mutants have demonstrated that these processes appear independent of the replication of nuclear DNA but not of its expression.", "contents": "Integration and regulation of mitochondrial assembly in yeast. The interactions between the mitochondrial and nucleocytoplasmic systems required for mitochondriogenesis have been investigated at several different levels. Those involved in the formation of functional enzyme complexes have been studied using cytochrome oxidase: this multimeric (2 X 7 and 2 X 6 subunits for enzymes from yeast and beef heart respectively) has been resolved, and the mitochondrial contribution has been shown to be dispensible for catalytic function proper. Using novel mutants, with a mitochondrial mode of inheritance, a mitochondrial gene product localized in the oligomycin-sensitive ATPase has been implicated in the assembly not only of this complex, but of cytochrome oxidase as well. Interactions required for the genetic competence of the mitochondrial system have become apparent as a result of studies in the mechanism of action of the highly effective mitochondrial mutagen ethidium bromide. This agent first becomes covalently inserted into mitochondrial DNA and, after its excision, eventually results in extensive degradation of the macromolecule. The excision reaction has now been shown to be performed by a complex between the oligomycin-sensitive ATPase and a DNA-binding protein presumably involved in recognizing the damage. On the level of replication and expression of the mitochondrial genome studies using thermolabile mutants have demonstrated that these processes appear independent of the replication of nuclear DNA but not of its expression."}
{"id": "PMID:192998", "title": "Structure of cytochrome c oxidase from baker's yeast - a progress report. Preparation of four subunits for amino acid sequence determination and attempts to localize the cytochrome c binding site.", "content": "Cytochrome c oxidase from the inner membrane of yeast mitochondria consists of seven nonidentical protein subunits, three being synthesized on mitochondrial ribosomes (molecular weights I: 43 K, II: 34 K, and III: 24 K) and four being made on cytoplasmic ribosomes (molecular weights IV: 14 K, V: 12 K, VI: 12 K, and VII: 4.5 K). In the present study all four cytoplasmically synthesized subunits of the enzyme were isolated on a large scale using ion exchange chromatography and gel filtration. Their amino acid composition as well as their amino- and carbosy-terminal amino acid residues have been determined. Sequence determinations of subunits IV and VI are already in an advanced state. The sequence of subunit VI is characterized by a large amino-terminal stretch dominated by charged amino acid residues followed by a cluster of hydrophobic amino acids. The binding site of yeast cytochrome oxidase for cytochrome c was studied by chemical crosslinking experiments. The formation of a disulfide bridge between the two proteins was observed by using cytochrome c from yeast modified with 5-thionitrobenzoate at the cysteinyl residue in position 107. Alternatively, a disulfide between yeast cytochrome c and the oxidase could be formed directly by oxidation with copper phenanthroline. Gel electrophoresis of the crosslinked complexes in sodium dodecyl sulfate revealed a new protein band with an apparent molecular weight of 38 K. This new band appears to be derived from cytochrome c and from subunit III of cytochrome oxidase.", "contents": "Structure of cytochrome c oxidase from baker's yeast - a progress report. Preparation of four subunits for amino acid sequence determination and attempts to localize the cytochrome c binding site. Cytochrome c oxidase from the inner membrane of yeast mitochondria consists of seven nonidentical protein subunits, three being synthesized on mitochondrial ribosomes (molecular weights I: 43 K, II: 34 K, and III: 24 K) and four being made on cytoplasmic ribosomes (molecular weights IV: 14 K, V: 12 K, VI: 12 K, and VII: 4.5 K). In the present study all four cytoplasmically synthesized subunits of the enzyme were isolated on a large scale using ion exchange chromatography and gel filtration. Their amino acid composition as well as their amino- and carbosy-terminal amino acid residues have been determined. Sequence determinations of subunits IV and VI are already in an advanced state. The sequence of subunit VI is characterized by a large amino-terminal stretch dominated by charged amino acid residues followed by a cluster of hydrophobic amino acids. The binding site of yeast cytochrome oxidase for cytochrome c was studied by chemical crosslinking experiments. The formation of a disulfide bridge between the two proteins was observed by using cytochrome c from yeast modified with 5-thionitrobenzoate at the cysteinyl residue in position 107. Alternatively, a disulfide between yeast cytochrome c and the oxidase could be formed directly by oxidation with copper phenanthroline. Gel electrophoresis of the crosslinked complexes in sodium dodecyl sulfate revealed a new protein band with an apparent molecular weight of 38 K. This new band appears to be derived from cytochrome c and from subunit III of cytochrome oxidase."}
{"id": "PMID:192999", "title": "Studies of the UV-sensitivity of virus-specific RNA synthesis in cells infected or transformed by adenovirus 5 and SV 40.", "content": "The effect of UV-irradiation on host and virus-specific RNA synthesis in cells infected or transformed by tumor viruses (Ad 5 and SV 40) was studied. It was found that the synthesis of host and Ad 5 RNA in infected KB cells was almost euqally inhibited upon UV-irradiation; the transcription of the EcoRI produced fragements--fragment B was inhibited to a greater extent than fragment A, suggesting that the transcription of the whole Ad 5 genome starts from the left side. The transcription of viral sequences in transformed cells, on the other hand, was more resistant to UV-irradiation than the transcription of the host ones. The results obtained suggest that the small size of the virus transcriptions, or their location at the beginning of large host transcriptions, may be responsible for the observed data.", "contents": "Studies of the UV-sensitivity of virus-specific RNA synthesis in cells infected or transformed by adenovirus 5 and SV 40. The effect of UV-irradiation on host and virus-specific RNA synthesis in cells infected or transformed by tumor viruses (Ad 5 and SV 40) was studied. It was found that the synthesis of host and Ad 5 RNA in infected KB cells was almost euqally inhibited upon UV-irradiation; the transcription of the EcoRI produced fragements--fragment B was inhibited to a greater extent than fragment A, suggesting that the transcription of the whole Ad 5 genome starts from the left side. The transcription of viral sequences in transformed cells, on the other hand, was more resistant to UV-irradiation than the transcription of the host ones. The results obtained suggest that the small size of the virus transcriptions, or their location at the beginning of large host transcriptions, may be responsible for the observed data."}
{"id": "PMID:193000", "title": "[A new diet for inducing early experimental atherosclerosis in rabbits].", "content": "Authors by a new combined diet consisting of cholesterol vitamin D3 and sour cream produced clinico-biochemical changes characteristic for atherosclerosis in a very short period in rabbits. This diet caused severe lipoproteinaemia, hypercholesterinaemia and microscopis and macroscopic changes in the aortic wall. Authors assume, that this diet is suitable for producin atherosclerosis in a short period.", "contents": "[A new diet for inducing early experimental atherosclerosis in rabbits]. Authors by a new combined diet consisting of cholesterol vitamin D3 and sour cream produced clinico-biochemical changes characteristic for atherosclerosis in a very short period in rabbits. This diet caused severe lipoproteinaemia, hypercholesterinaemia and microscopis and macroscopic changes in the aortic wall. Authors assume, that this diet is suitable for producin atherosclerosis in a short period."}
{"id": "PMID:193001", "title": "Immunoblastic lymphadenopathy with centrofollicular PAS-positive inclusions.", "content": "The authors describe the clinical and histopathologic picture of immunoblastic lymphadenomegaly in a 66-year-old patient with allergic antecedents. The condition of the patient ameliorated following cortisone and antibiotic therapy, but adenomegalia relapsed after several months. PAS-positive granular inclusions were found in the macrophage cells in the germinative centres of the follicles, showing the aspect of a blockade with nuclear significance.", "contents": "Immunoblastic lymphadenopathy with centrofollicular PAS-positive inclusions. The authors describe the clinical and histopathologic picture of immunoblastic lymphadenomegaly in a 66-year-old patient with allergic antecedents. The condition of the patient ameliorated following cortisone and antibiotic therapy, but adenomegalia relapsed after several months. PAS-positive granular inclusions were found in the macrophage cells in the germinative centres of the follicles, showing the aspect of a blockade with nuclear significance."}
{"id": "PMID:193004", "title": "Congenital cytomegalovirus infection.", "content": "The overall prevalence of congenital cytomegalovirus infection among the offspring of a highly immune young female population was 2.4 per cent (23 of 939). To ascertain whether the presence of anticytomegalovirus antibodies protects the developing fetus, we examined the offspring of 239 prospectively studied women. Despite substantial levels of preconceptional antibodies, intrauterine cytomegalovirus infection occured in seven of 208 (3.4 per cent) seroimmune women. Three neonates with congenital infection were born to 31 initially seronegative women. All the congenitally infected infants had subclinical involvement. Maternal humoral immunity may not protect the fetus against congenital cytomegalovirus infection. Neutralization kinetics and restriction enzyme analysis with endonucleases (EcoR-1 and HinD 111) demonstrated antigenic and genetic homology between viral strains isolated from two siblings consecutively infected in utero, indicating that repeat maternal infection with the same virus is transmissible to sequential products of conception.", "contents": "Congenital cytomegalovirus infection. The overall prevalence of congenital cytomegalovirus infection among the offspring of a highly immune young female population was 2.4 per cent (23 of 939). To ascertain whether the presence of anticytomegalovirus antibodies protects the developing fetus, we examined the offspring of 239 prospectively studied women. Despite substantial levels of preconceptional antibodies, intrauterine cytomegalovirus infection occured in seven of 208 (3.4 per cent) seroimmune women. Three neonates with congenital infection were born to 31 initially seronegative women. All the congenitally infected infants had subclinical involvement. Maternal humoral immunity may not protect the fetus against congenital cytomegalovirus infection. Neutralization kinetics and restriction enzyme analysis with endonucleases (EcoR-1 and HinD 111) demonstrated antigenic and genetic homology between viral strains isolated from two siblings consecutively infected in utero, indicating that repeat maternal infection with the same virus is transmissible to sequential products of conception."}
{"id": "PMID:193007", "title": "Hypoglycemia of infancy and nesidioblastosis. Studies with somatostatin.", "content": "We treated a two-month-old infant with servere intractable hypoglycemia and nesidioblastosis with continuous glucose infusions (0.75 g per kilogram per hour) via a central venous catheter. Preprandial glucose levels on this regimen were 37+/-2 mg per deciliter (+/-S.E.M.). Basal serum insulin levels were within normal fasting levels for this age group but inappropriately elevated for the blood glucose levels. The beta cells were exquisitely sensitive to infusions of synthetic cyclic somatostatin, with a dose-dependent rise in blood glucose and concomitant suppression of serum insulin levels. There was only minimal suppression of plasma glucagon levels. Single subcutaneous injections of 50 microng of protamine zinc somatostatin raised preprandial blood glucose levels to 83+/-3 mg per deciliter for four to five days although preprandial hormone levels were unchanged. These findings indicate that hypoglycemia of infancy is a hyperinsulin state with abnormal basal regulation of insulin secretion.", "contents": "Hypoglycemia of infancy and nesidioblastosis. Studies with somatostatin. We treated a two-month-old infant with servere intractable hypoglycemia and nesidioblastosis with continuous glucose infusions (0.75 g per kilogram per hour) via a central venous catheter. Preprandial glucose levels on this regimen were 37+/-2 mg per deciliter (+/-S.E.M.). Basal serum insulin levels were within normal fasting levels for this age group but inappropriately elevated for the blood glucose levels. The beta cells were exquisitely sensitive to infusions of synthetic cyclic somatostatin, with a dose-dependent rise in blood glucose and concomitant suppression of serum insulin levels. There was only minimal suppression of plasma glucagon levels. Single subcutaneous injections of 50 microng of protamine zinc somatostatin raised preprandial blood glucose levels to 83+/-3 mg per deciliter for four to five days although preprandial hormone levels were unchanged. These findings indicate that hypoglycemia of infancy is a hyperinsulin state with abnormal basal regulation of insulin secretion."}
{"id": "PMID:193008", "title": "Cellular immunity and herpesvirus infections in cardiac-transplant patients.", "content": "We observed severe infection with herpes simplex virus in cardiac-transplant patients despite their high serum antibody levels to this virus. Therefore, we sought to correlate clinical susceptibility to two herpesvirus (simplex and zoster) infections with specific cellular immunity, assessed by the transformation and interferon responses of peripheral blood mononuclear cells to heat-inactivated antigens. Transformation and interferon response to herps simplex virus was maximally depressed immediately after transplantation, the time when severe and prolonged infection with herps simplex virus occurred. Six months to six years after transplantation, both clinical susceptibility and cellular immunity to herpes simplex virus were normal. Herpes zoster infections were more frequent than normal at all times after cardiac transplantation; depressed or absent cellular responses to the varicella zoster virus paralleled that susceptibility. In these patients the risk of severe herpesvirus infections correlated with depressed cellular immune responses to the specific viral agent involved.", "contents": "Cellular immunity and herpesvirus infections in cardiac-transplant patients. We observed severe infection with herpes simplex virus in cardiac-transplant patients despite their high serum antibody levels to this virus. Therefore, we sought to correlate clinical susceptibility to two herpesvirus (simplex and zoster) infections with specific cellular immunity, assessed by the transformation and interferon responses of peripheral blood mononuclear cells to heat-inactivated antigens. Transformation and interferon response to herps simplex virus was maximally depressed immediately after transplantation, the time when severe and prolonged infection with herps simplex virus occurred. Six months to six years after transplantation, both clinical susceptibility and cellular immunity to herpes simplex virus were normal. Herpes zoster infections were more frequent than normal at all times after cardiac transplantation; depressed or absent cellular responses to the varicella zoster virus paralleled that susceptibility. In these patients the risk of severe herpesvirus infections correlated with depressed cellular immune responses to the specific viral agent involved."}
{"id": "PMID:193014", "title": "[Determination of vitamin D3 in premixes and mixed feeds].", "content": "The authors developed a two-dimensional thin-layer chromatographic method for the qualitative and quantitative determination of vitamin D3 in premixes and mixed feeds. The procedure permits to determine I.U. = 0.128 micrograms of vitamin D3. The method is illustrated by the description of the analyses of 3 premixes and 5 mixed feeds.", "contents": "[Determination of vitamin D3 in premixes and mixed feeds]. The authors developed a two-dimensional thin-layer chromatographic method for the qualitative and quantitative determination of vitamin D3 in premixes and mixed feeds. The procedure permits to determine I.U. = 0.128 micrograms of vitamin D3. The method is illustrated by the description of the analyses of 3 premixes and 5 mixed feeds."}
{"id": "PMID:193015", "title": "[Antistatic finishing of plastics from food hygiene and toxicological viewpoints].", "content": "The authors investigated experimentally the migration behaviour of formed plastics with antistatic finish. The degree of molecular coating on the surface and the rate of diffusion of the antistatics used (ethoxylated amines and alkyl sulphonate) were calculated from the results of washing-off and continuous extraction experiments. The findings are indicative of a good depot effect, i.e. the antistatic action is steadily regenerated by secondary migration. Certain agents such as  polyethylene glycol enhance diffusion whereby the values for the migration in normal polystyrene are increased; but this increase is acceptable from the viewpoint of safety. In impact polystyrene, the limiting value for total migration is largely exceeded so that considerable contamination may be expected when it comes in contact with foods. From the viewpoint of food-toxicology, there are concerns about the high specific migration values of alkyl sulphonate. For this reason, its use in the food sector should be limited to such cases where direct contact with foods is excluded.", "contents": "[Antistatic finishing of plastics from food hygiene and toxicological viewpoints]. The authors investigated experimentally the migration behaviour of formed plastics with antistatic finish. The degree of molecular coating on the surface and the rate of diffusion of the antistatics used (ethoxylated amines and alkyl sulphonate) were calculated from the results of washing-off and continuous extraction experiments. The findings are indicative of a good depot effect, i.e. the antistatic action is steadily regenerated by secondary migration. Certain agents such as  polyethylene glycol enhance diffusion whereby the values for the migration in normal polystyrene are increased; but this increase is acceptable from the viewpoint of safety. In impact polystyrene, the limiting value for total migration is largely exceeded so that considerable contamination may be expected when it comes in contact with foods. From the viewpoint of food-toxicology, there are concerns about the high specific migration values of alkyl sulphonate. For this reason, its use in the food sector should be limited to such cases where direct contact with foods is excluded."}
{"id": "PMID:193016", "title": "Immune surveillance--a powerful mechanism with a limited range.", "content": "There is excellent evidence for the belief that immune surveillance mechanisms prevent the outgrowth of potentially neoplastic cells induced by horizontally transmitted, ubiquitous, potentially oncogenic viruses, indigenous to natural populations. Polyoma virus in mice, Marek's disease in the chicken, Herpesvirus saimiri in the squirrel monkey, and the Epstein-Barr virus in man are examples. There is much less evidence for immune surveillance against chemically induced tumors. It is argued that surveillance against the virus-induced tumors may have evolved by the selective fixation of appropriate immune responsiveness (IR) genes. It is important to distinguish between the breakdown of an existing surveillance mechanism, e.g., by immunosuppresion, and the lack of immune recognition, due to the deficiency of the IR gene equipment. Presently available in vitro lymphocytotoxicity tests are not yet developed to the point where they can reliably distinguish between these alternatives.", "contents": "Immune surveillance--a powerful mechanism with a limited range. There is excellent evidence for the belief that immune surveillance mechanisms prevent the outgrowth of potentially neoplastic cells induced by horizontally transmitted, ubiquitous, potentially oncogenic viruses, indigenous to natural populations. Polyoma virus in mice, Marek's disease in the chicken, Herpesvirus saimiri in the squirrel monkey, and the Epstein-Barr virus in man are examples. There is much less evidence for immune surveillance against chemically induced tumors. It is argued that surveillance against the virus-induced tumors may have evolved by the selective fixation of appropriate immune responsiveness (IR) genes. It is important to distinguish between the breakdown of an existing surveillance mechanism, e.g., by immunosuppresion, and the lack of immune recognition, due to the deficiency of the IR gene equipment. Presently available in vitro lymphocytotoxicity tests are not yet developed to the point where they can reliably distinguish between these alternatives."}
{"id": "PMID:193017", "title": "Spontaneous tumor regression: possible relationship to in vitro parameters of tumor immunity.", "content": "Evidence is discussed from three animal systems (Shope papillomas in rabbits, Moloney sarcomas in mice, Schmidt-Ruppin-Rous sarcomas in Japanese quail) that immune reactions can be important in spontaneous tumor regression. In vitro studies performed in these systems indicate that blocking serum factors can thwart cell-mediated immune responses and that \"unblocking\" antibodies are often found in animals whose tumors have regressed. To what extent spontaneous regressions of human neoplasms are due to immunologic mechanisms is unknown; in 2 patients who had undergone spontaneous tumor regression, tumor cell cytotoxic lymphocytes and unblocking serum factors were detected. Better animal models and better knowledge about the mechanisms of tumor immune reactions are needed before tumor regression can be more successfully induced by immunologic manipulation (to what extent that will even be feasible in man is unknown).", "contents": "Spontaneous tumor regression: possible relationship to in vitro parameters of tumor immunity. Evidence is discussed from three animal systems (Shope papillomas in rabbits, Moloney sarcomas in mice, Schmidt-Ruppin-Rous sarcomas in Japanese quail) that immune reactions can be important in spontaneous tumor regression. In vitro studies performed in these systems indicate that blocking serum factors can thwart cell-mediated immune responses and that \"unblocking\" antibodies are often found in animals whose tumors have regressed. To what extent spontaneous regressions of human neoplasms are due to immunologic mechanisms is unknown; in 2 patients who had undergone spontaneous tumor regression, tumor cell cytotoxic lymphocytes and unblocking serum factors were detected. Better animal models and better knowledge about the mechanisms of tumor immune reactions are needed before tumor regression can be more successfully induced by immunologic manipulation (to what extent that will even be feasible in man is unknown)."}
{"id": "PMID:193018", "title": "Mechanisms of escape from immune surveillance.", "content": "The escape from immune rejection is, like the development of drug resistance in microorganisms, a multi-pathway process. Selection favors the phenotype, i.e., the cell that can grow in spite of the immune rejection process, not the underlying mechanism. Experimental evidence documents the roles of host immunosuppression (genetic or environmental), immunoresistance at the cellular level, \"sneaking through\" (i.e., growth of a tumor to irreversible size prior to the mobilization of an appropriate immune response), lack of antigenic recognition, and blocking enhancement type reactions.", "contents": "Mechanisms of escape from immune surveillance. The escape from immune rejection is, like the development of drug resistance in microorganisms, a multi-pathway process. Selection favors the phenotype, i.e., the cell that can grow in spite of the immune rejection process, not the underlying mechanism. Experimental evidence documents the roles of host immunosuppression (genetic or environmental), immunoresistance at the cellular level, \"sneaking through\" (i.e., growth of a tumor to irreversible size prior to the mobilization of an appropriate immune response), lack of antigenic recognition, and blocking enhancement type reactions."}
{"id": "PMID:193020", "title": "A pathologist looks at spontaneous regression of cancer.", "content": "We  are all subjected to varying amounts of mutating, potential cancer-inducing events, which are cumulative. In most instances, the accumulations are repaired or are lethal. If a viable clone survives, it must proliferate in order to become manifest and eventually to overpower the host's normal regulatory and defense mechanisms. The proliferation may be incited and sustained by cocarcinogens, hormone excess, chronic infections such as schistosomiasis, and in the case of lymphoid cells, by immune incompetence. On the other side are the protective reparing enzymes, which serve to cut out the damaged segments of DNA and repair them as fast as they can. The normal homeostatic mechanisms tend to keep cell proliferation and activity within the beneficial bounds of need. The controlling forces that cause cells to stop reproducing themselves and differentiate to perform a useful function also tend to slow or even stop the useless proliferation if all the cells can undergo maturation to a postmitotic state. There are also the protective mechanisms of immunity: Sensitized B lymphocytes tag the antigenic sites of tumor cells and activate the T-cell macrophages to destroy the tagged cells.", "contents": "A pathologist looks at spontaneous regression of cancer. We  are all subjected to varying amounts of mutating, potential cancer-inducing events, which are cumulative. In most instances, the accumulations are repaired or are lethal. If a viable clone survives, it must proliferate in order to become manifest and eventually to overpower the host's normal regulatory and defense mechanisms. The proliferation may be incited and sustained by cocarcinogens, hormone excess, chronic infections such as schistosomiasis, and in the case of lymphoid cells, by immune incompetence. On the other side are the protective reparing enzymes, which serve to cut out the damaged segments of DNA and repair them as fast as they can. The normal homeostatic mechanisms tend to keep cell proliferation and activity within the beneficial bounds of need. The controlling forces that cause cells to stop reproducing themselves and differentiate to perform a useful function also tend to slow or even stop the useless proliferation if all the cells can undergo maturation to a postmitotic state. There are also the protective mechanisms of immunity: Sensitized B lymphocytes tag the antigenic sites of tumor cells and activate the T-cell macrophages to destroy the tagged cells."}
{"id": "PMID:193021", "title": "Spontaneous regression of bronchogenic carcinoma.", "content": "Two cases of spontaneous regression of bronchogenic carcinoma were discovered in the literature, and the pertinent findings are described. Six equivocal cases of spontaneous regression are also presented. The reasons for the scarcity of spontaneous regression of bronchogenic carcinoma are discussed; no apparent reasons for spontaneous regression in these two cases could be determined.", "contents": "Spontaneous regression of bronchogenic carcinoma. Two cases of spontaneous regression of bronchogenic carcinoma were discovered in the literature, and the pertinent findings are described. Six equivocal cases of spontaneous regression are also presented. The reasons for the scarcity of spontaneous regression of bronchogenic carcinoma are discussed; no apparent reasons for spontaneous regression in these two cases could be determined."}
{"id": "PMID:193022", "title": "Spontaneous regression in choriocarcinoma and related gestational trophobalstic neoplasms.", "content": "Gestational trophoblastic neoplasia represents a biologic spectrum of tumors progressing from the hydatid mole, to invasive mole, and to choriocarcinoma. This progression is reflected in increasing degrees of aneuploidy in the respective lesions. Just as there is a natural tendency for the rejection of the trophoblast of a normal pregnancy culminating either in parturition or in spontaneous abortion, rejection of tumors of trophoblast occurs at any point in the progression of the disease spectrum. The unusual effectiveness of chemotherapy in trophoblastic disease may be related to this natural tendency to rejection. This tendency, in turn, is thought to derive from the genetic disparity between the maternal host and the tumor tissue of fetal origin, since the fetus possesses both maternal and fetal antigens.", "contents": "Spontaneous regression in choriocarcinoma and related gestational trophobalstic neoplasms. Gestational trophoblastic neoplasia represents a biologic spectrum of tumors progressing from the hydatid mole, to invasive mole, and to choriocarcinoma. This progression is reflected in increasing degrees of aneuploidy in the respective lesions. Just as there is a natural tendency for the rejection of the trophoblast of a normal pregnancy culminating either in parturition or in spontaneous abortion, rejection of tumors of trophoblast occurs at any point in the progression of the disease spectrum. The unusual effectiveness of chemotherapy in trophoblastic disease may be related to this natural tendency to rejection. This tendency, in turn, is thought to derive from the genetic disparity between the maternal host and the tumor tissue of fetal origin, since the fetus possesses both maternal and fetal antigens."}
{"id": "PMID:193026", "title": "Photochemical attachment of cyclic AMP binding protein(s) to the nuclear genome.", "content": "The nature of the cyclic AMP-receptor-nucleus interactions was examined by a novel combination of two photoreactions. A photosensitive derivative of cyclic AMP, N6-butyryl cyclic AMP, was covalently attached to its cytoplasmic receptod by photo-affinity labelling and this receptor complex was photo-crosslinked by the DNA in the rat liver nuclei. The photolytic reactions seemed to be specific since stable links were formed only when substantial noncovalent binding occured.", "contents": "Photochemical attachment of cyclic AMP binding protein(s) to the nuclear genome. The nature of the cyclic AMP-receptor-nucleus interactions was examined by a novel combination of two photoreactions. A photosensitive derivative of cyclic AMP, N6-butyryl cyclic AMP, was covalently attached to its cytoplasmic receptod by photo-affinity labelling and this receptor complex was photo-crosslinked by the DNA in the rat liver nuclei. The photolytic reactions seemed to be specific since stable links were formed only when substantial noncovalent binding occured."}
{"id": "PMID:193030", "title": "Sequence and structure of D-glyceraldehyde 3-phosphate dehydrogenase from Bacillus stearothermophilus.", "content": "The glyceraldehyde 3-phosphate dehydogenase holoenzyme of Bacillus stearothermophilus possesses precise 222 symmetry: in this respect it differs from the reported structure of the lobster muscle enzyme. Pairs of active sites are linked through a flexible polypeptide loop which probably mediates the structural changes giving rise to cooperative effects. Three additional salt bridges made by each subunit to others would make a major contribution to thermostability of the tetramer.", "contents": "Sequence and structure of D-glyceraldehyde 3-phosphate dehydrogenase from Bacillus stearothermophilus. The glyceraldehyde 3-phosphate dehydogenase holoenzyme of Bacillus stearothermophilus possesses precise 222 symmetry: in this respect it differs from the reported structure of the lobster muscle enzyme. Pairs of active sites are linked through a flexible polypeptide loop which probably mediates the structural changes giving rise to cooperative effects. Three additional salt bridges made by each subunit to others would make a major contribution to thermostability of the tetramer."}
{"id": "PMID:193039", "title": "Polymorphism of the major envelope glycoprotein (gp70) of murine C-type viruses: virion associated and differentiation antigens encoded by a multi-gene family.", "content": "Structural comparison of the major envelope glycoproteins (gp70) from 35 different murine type C viruses and free gp70 expressed at various anatomical sites in the mouse showed that the gp70s are polymorphic products of a large multi-gene family encoding viral and differentiation antigens. Different proviruses are expressed in cells following distinct pathways of differentiation. When the various gp70s are grouped according to primary structure they fall naturally into viral host range classes, confirming the suspicion that C-type viral tropism is largely determined by the nature of the gp70 product expressed.", "contents": "Polymorphism of the major envelope glycoprotein (gp70) of murine C-type viruses: virion associated and differentiation antigens encoded by a multi-gene family. Structural comparison of the major envelope glycoproteins (gp70) from 35 different murine type C viruses and free gp70 expressed at various anatomical sites in the mouse showed that the gp70s are polymorphic products of a large multi-gene family encoding viral and differentiation antigens. Different proviruses are expressed in cells following distinct pathways of differentiation. When the various gp70s are grouped according to primary structure they fall naturally into viral host range classes, confirming the suspicion that C-type viral tropism is largely determined by the nature of the gp70 product expressed."}
{"id": "PMID:193046", "title": "Dopamine\"autoreceptors\": pharmacological characterization by microiontophoretic single cell recording studies.", "content": "The effects on the firing of single dopamine (DA) neurons in the substantia nigra (and adjacent ventral tegmental area) of a representative group of catecholamine agonists and antagonists were studied in rats using single cell recording and microiontophoretic techniques. Microiontophoretic application of DA or the DA agonist apomorphine depressed the firing of these cells; the DA antagonist trifluoperazine blocked this effect. However, the alpha-agonist clonidine had no depressant effect and the beta-agonist isoproteronol had only a weak depressant action on DA neurons. Furthermore, the alpha-antagonist piperoxane and the beta-antagonist sotolol were completely ineffective in blocking the depressant effects of DA. These results show that DA-sensitive receptors on the soma of DA neurons are pharmacologically distinct from alpha or beta adrenoreceptors. Because of their location and selective responsiveness to DA agonists, the catecholamine receptors on the soma of DA neurons appear best classified as DA \"autoreceptors\".", "contents": "Dopamine\"autoreceptors\": pharmacological characterization by microiontophoretic single cell recording studies. The effects on the firing of single dopamine (DA) neurons in the substantia nigra (and adjacent ventral tegmental area) of a representative group of catecholamine agonists and antagonists were studied in rats using single cell recording and microiontophoretic techniques. Microiontophoretic application of DA or the DA agonist apomorphine depressed the firing of these cells; the DA antagonist trifluoperazine blocked this effect. However, the alpha-agonist clonidine had no depressant effect and the beta-agonist isoproteronol had only a weak depressant action on DA neurons. Furthermore, the alpha-antagonist piperoxane and the beta-antagonist sotolol were completely ineffective in blocking the depressant effects of DA. These results show that DA-sensitive receptors on the soma of DA neurons are pharmacologically distinct from alpha or beta adrenoreceptors. Because of their location and selective responsiveness to DA agonists, the catecholamine receptors on the soma of DA neurons appear best classified as DA \"autoreceptors\"."}
{"id": "PMID:193047", "title": "Possible feed-back inhibition of noradrenaline release by purine compounds.", "content": "The contractile responses to transmural stimulation of, and the overflow of tritium from the rat portal vein prelabelled with 3H-noradrenaline were studied. The contractile responses of the rat portal vein were sustained throughout the period of stimulation. The tension developed did not decline when two consecutive periods of stimulation were compared. In contrast, the tritium overflow decreased during the second period of stimulation. Preincubation with 3 micronM phenoxybenzamine during 30 min increased 3-fold the tritium overflow during stimulation. Phentolamine and phenoxybenzamine were nearly equipotent in reducing the vascular response to stimulation. In contrast, phentolamine was less potent than phenoxybenzamine in increasing the 3H-noradrenaline overflow elicited by stimulation. The results obtained with phentolamine are interpreted in terms of a different potency of phentolamine to produce blockade of prejunctional and postjunctional alpha-adrenoceptors in the rat portal vein. ATP inhibited by 70% the tritium overflow induced by stimulation. The potency of ATP in inhibiting the overflow increased when the prejunction alpha-adrenoceptors were blocked. The purine compounds ATP, ADP, AMP and adenosine were roughly equipotent in inhibiting stimulation-induced tritium overflow. The tritium released by stimulation decreased when uptake and metabolism of adenosine were inhibited. Under physiological conditions, a prejunctional purinergic inhibition of noradrenaline release might be involved in an endogenously mediated negative feed-back regulatory mechanism. It is possible that the purinergic inhibition of the noradrenaline liberation elicited by stimulation plays a physiological role in tissues with both purinergic and adrenergic innervation.", "contents": "Possible feed-back inhibition of noradrenaline release by purine compounds. The contractile responses to transmural stimulation of, and the overflow of tritium from the rat portal vein prelabelled with 3H-noradrenaline were studied. The contractile responses of the rat portal vein were sustained throughout the period of stimulation. The tension developed did not decline when two consecutive periods of stimulation were compared. In contrast, the tritium overflow decreased during the second period of stimulation. Preincubation with 3 micronM phenoxybenzamine during 30 min increased 3-fold the tritium overflow during stimulation. Phentolamine and phenoxybenzamine were nearly equipotent in reducing the vascular response to stimulation. In contrast, phentolamine was less potent than phenoxybenzamine in increasing the 3H-noradrenaline overflow elicited by stimulation. The results obtained with phentolamine are interpreted in terms of a different potency of phentolamine to produce blockade of prejunctional and postjunctional alpha-adrenoceptors in the rat portal vein. ATP inhibited by 70% the tritium overflow induced by stimulation. The potency of ATP in inhibiting the overflow increased when the prejunction alpha-adrenoceptors were blocked. The purine compounds ATP, ADP, AMP and adenosine were roughly equipotent in inhibiting stimulation-induced tritium overflow. The tritium released by stimulation decreased when uptake and metabolism of adenosine were inhibited. Under physiological conditions, a prejunctional purinergic inhibition of noradrenaline release might be involved in an endogenously mediated negative feed-back regulatory mechanism. It is possible that the purinergic inhibition of the noradrenaline liberation elicited by stimulation plays a physiological role in tissues with both purinergic and adrenergic innervation."}
{"id": "PMID:193048", "title": "The effect of metacaine (MS-222) on the activity of the efferent and afferent nerves in the teleost lateral-line system.", "content": "1. Free-swimming fish (Tilapia leucosticta and Rutilus rutilus) were used to determine threshold concentrations required for general anesthesia with metacaine (MS-222). The criterion for anesthesia was reached at a concentration of 1:1500 (w/w) with both fish, although the symptoms were somewhat more pronounced in Rutilus. 2. Recordings of efferent spontaneous activity in the lateral-line nerve were used as a measure of the central effect of metacaine during administration in the respiratory stream, as compared with respiration of fresh water. The reduction of activity at the end of a 3-min exposure to the drug was 70%. 3. Maximum recovery (90% of the initial activity) was reached after 30 min application of fresh water. 4. The various efferent impulse types were differentially affected by the anesthetic. 5. Direct recordings from sound-sensitive neurons in the medulla confirm the strong central effect of metacaine. 6. Irrigation of the lateral-line system with anesthetic solution also produced a reduction in afferent spontaneous activity; there was a distinct peripheral effect even at the threshold concentration. 7. Reactions of trigeminal nerve fibers to mechanical stimulation of the skin were reduced after application of a metacaine solution to the skin. This finding confirms the local anesthetic effect of the drug. 8. The anesthetic solution at a given concentration had a greater effect on the CNS than on the peripheral receptors. 9. The implications of the results with respect to the risk of misjudging the depth of general anesthesia are discussed. 10. Because of the complexity of its anesthetic efficacy, it is recommended that metacaine not be used for neurophysiological investigations, but rather that the animals be immobilized by means of muscle relaxants.", "contents": "The effect of metacaine (MS-222) on the activity of the efferent and afferent nerves in the teleost lateral-line system. 1. Free-swimming fish (Tilapia leucosticta and Rutilus rutilus) were used to determine threshold concentrations required for general anesthesia with metacaine (MS-222). The criterion for anesthesia was reached at a concentration of 1:1500 (w/w) with both fish, although the symptoms were somewhat more pronounced in Rutilus. 2. Recordings of efferent spontaneous activity in the lateral-line nerve were used as a measure of the central effect of metacaine during administration in the respiratory stream, as compared with respiration of fresh water. The reduction of activity at the end of a 3-min exposure to the drug was 70%. 3. Maximum recovery (90% of the initial activity) was reached after 30 min application of fresh water. 4. The various efferent impulse types were differentially affected by the anesthetic. 5. Direct recordings from sound-sensitive neurons in the medulla confirm the strong central effect of metacaine. 6. Irrigation of the lateral-line system with anesthetic solution also produced a reduction in afferent spontaneous activity; there was a distinct peripheral effect even at the threshold concentration. 7. Reactions of trigeminal nerve fibers to mechanical stimulation of the skin were reduced after application of a metacaine solution to the skin. This finding confirms the local anesthetic effect of the drug. 8. The anesthetic solution at a given concentration had a greater effect on the CNS than on the peripheral receptors. 9. The implications of the results with respect to the risk of misjudging the depth of general anesthesia are discussed. 10. Because of the complexity of its anesthetic efficacy, it is recommended that metacaine not be used for neurophysiological investigations, but rather that the animals be immobilized by means of muscle relaxants."}
{"id": "PMID:193049", "title": "The actions of aminopyridines on avian muscle.", "content": "The effects of 2-, 3-, and 4-aminopyridines were investigated on the isolated chick biventer cervicis nerve-muscle preparation and on nerve-free cell cultures of embryonic chick skeletal muscle.  All 3 compounds reversed tubocurarine blockade and augmented twitch height in indirectly stimulated biventer cervicis preparations. 4-Aminopyridine was approximately 10 times more potent than 2-, or 3-aminopyridine. Twitch augmentation was also seen in directly stimulated preparations but to a much lesser extent. The compounds did not have significant anticholinesterase activity, nor did they have any depolarizing activity when tested on nerve-free cultured muscle fibres. At high concentrations the aminopyridines produced a maintained contracture in the biventer preparations which was enhanced by neostigmine and inhibited by tubocurarine. It is suggested that the aminopyridines facilitate neuromuscular transmission by increasing acetylcholine release in response to nerve stimulation, and that the compounds can also increase spontaneous transmitter release.", "contents": "The actions of aminopyridines on avian muscle. The effects of 2-, 3-, and 4-aminopyridines were investigated on the isolated chick biventer cervicis nerve-muscle preparation and on nerve-free cell cultures of embryonic chick skeletal muscle.  All 3 compounds reversed tubocurarine blockade and augmented twitch height in indirectly stimulated biventer cervicis preparations. 4-Aminopyridine was approximately 10 times more potent than 2-, or 3-aminopyridine. Twitch augmentation was also seen in directly stimulated preparations but to a much lesser extent. The compounds did not have significant anticholinesterase activity, nor did they have any depolarizing activity when tested on nerve-free cultured muscle fibres. At high concentrations the aminopyridines produced a maintained contracture in the biventer preparations which was enhanced by neostigmine and inhibited by tubocurarine. It is suggested that the aminopyridines facilitate neuromuscular transmission by increasing acetylcholine release in response to nerve stimulation, and that the compounds can also increase spontaneous transmitter release."}
{"id": "PMID:193050", "title": "Catecholamine synthesis in rat brain after axotomy: interaction between apomorphine and haloperidol.", "content": "Axotomy of the ascending monoaminergic fibers by means of a complete cerebral hemitransection stimulated the formation of dopa during 30 min after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCl, 100 mg/kg i.p., in c. striatum and the dopamine-rich part of the limbic system. Apomorphine, 0.5 mg/kg i.p., antagonized the accumulation of dopa not only on the intact but also on the lesioned side. Haloperidol, 2 mg/kg i.p., stimulated dopa accumulation on the intact side but could not further stimulate the increase in dopa caused by transection. When both drugs were given together, the inhibitory effect of apomorphine was fully counteracted by haloperidol on both sides. In the predominantly noradrenaline-innervated occipito-temporal cortex dopa formation was slightly higher on the lesioned than on the intact side and was not markedly influenced by apomorphine. In the rest of the hemispheres the apomorphine-induced decrease in  dopa formation was more pronounced on the intact than on the lesioned side and was fully antagonized by haloperidol. The dopamine concentration was slightly higher in the lesioned c. striatum as compared to the intact side irrespective of the drugs administered. In c. striatum and the limbic system haloperidol caused a decrease in dopamine on the intact side which was not antagonized by additional treatment with apomorphine. Hemitransection caused a decrease in noradrenaline especially in the hemisphere portion. Neither apomorphine nor haloperidol or both drugs in combination changed the latter effect. In general, the tyrosine concentration tended to be higher on the lesioned than on the  intact side in all brain structures investigated. The data support the view that a local receptor-mediated feedback mechanism exists which is controlling dopamine synthesis even in the absence of impulse flow.", "contents": "Catecholamine synthesis in rat brain after axotomy: interaction between apomorphine and haloperidol. Axotomy of the ascending monoaminergic fibers by means of a complete cerebral hemitransection stimulated the formation of dopa during 30 min after inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCl, 100 mg/kg i.p., in c. striatum and the dopamine-rich part of the limbic system. Apomorphine, 0.5 mg/kg i.p., antagonized the accumulation of dopa not only on the intact but also on the lesioned side. Haloperidol, 2 mg/kg i.p., stimulated dopa accumulation on the intact side but could not further stimulate the increase in dopa caused by transection. When both drugs were given together, the inhibitory effect of apomorphine was fully counteracted by haloperidol on both sides. In the predominantly noradrenaline-innervated occipito-temporal cortex dopa formation was slightly higher on the lesioned than on the intact side and was not markedly influenced by apomorphine. In the rest of the hemispheres the apomorphine-induced decrease in  dopa formation was more pronounced on the intact than on the lesioned side and was fully antagonized by haloperidol. The dopamine concentration was slightly higher in the lesioned c. striatum as compared to the intact side irrespective of the drugs administered. In c. striatum and the limbic system haloperidol caused a decrease in dopamine on the intact side which was not antagonized by additional treatment with apomorphine. Hemitransection caused a decrease in noradrenaline especially in the hemisphere portion. Neither apomorphine nor haloperidol or both drugs in combination changed the latter effect. In general, the tyrosine concentration tended to be higher on the lesioned than on the  intact side in all brain structures investigated. The data support the view that a local receptor-mediated feedback mechanism exists which is controlling dopamine synthesis even in the absence of impulse flow."}
{"id": "PMID:193054", "title": "Opiate receptor identification in vitro and in vivo.", "content": "Using tritiated opiates with a high specific radioactivity, a high affinity binding to brain homogenates has been observed in vitro. Strong evidence was given that this type of binding is due to the interaction of labelled opiates with their specific receptors in the brain, since the ability of a wide variety of opiates to inhibit this binding corresponds very well with the potency of the drugs to produce their pharmacological effects in vivo. We have found that the simultaneous injection of labelled opiates into animals together with high doses of nonradioactive opiates decreases the brain concentration of the labelled drug. This displacement from brain satisfies criteria similar to those used for the identification of the opiate receptor in vitro. Furthermore, opiates produce their pharmacological effects in the same dose range in which they are able to displace a radiolabelled opiate from the brain. This strongly suggests that the receptor occupation by opiates can be identified by concentration changes in the brain of living animals.", "contents": "Opiate receptor identification in vitro and in vivo. Using tritiated opiates with a high specific radioactivity, a high affinity binding to brain homogenates has been observed in vitro. Strong evidence was given that this type of binding is due to the interaction of labelled opiates with their specific receptors in the brain, since the ability of a wide variety of opiates to inhibit this binding corresponds very well with the potency of the drugs to produce their pharmacological effects in vivo. We have found that the simultaneous injection of labelled opiates into animals together with high doses of nonradioactive opiates decreases the brain concentration of the labelled drug. This displacement from brain satisfies criteria similar to those used for the identification of the opiate receptor in vitro. Furthermore, opiates produce their pharmacological effects in the same dose range in which they are able to displace a radiolabelled opiate from the brain. This strongly suggests that the receptor occupation by opiates can be identified by concentration changes in the brain of living animals."}
{"id": "PMID:193055", "title": "Endogenous ligands of opiate receptors.", "content": "From brain and from pituitary tissue of vertebrates several peptides - with molecular weights between 500 and 3500 daltons - have been isolated, which behave like opiates in opiate receptor binding assays, in isolated tissue preparations and in the intact animal.", "contents": "Endogenous ligands of opiate receptors. From brain and from pituitary tissue of vertebrates several peptides - with molecular weights between 500 and 3500 daltons - have been isolated, which behave like opiates in opiate receptor binding assays, in isolated tissue preparations and in the intact animal."}
{"id": "PMID:193059", "title": "[Transmission of reticulofugal activity through the ventromedial group of propriospinal neurons in cats].", "content": "Responses of propriospinal interneurons localized in the ventromedial regions of the cat lumbar cord to the reticulospinal tract stimulation were studied. Monosynaptic excitatory action usually accompanied by di- and polysynaptic components was found in most units. Strong single stimuli were able to evoke discharges only in some cells, while temporal summation was necessary in many others. Excitation of neurons was followed by a short postactivation inhibition limiting the maximal discharge frequency.", "contents": "[Transmission of reticulofugal activity through the ventromedial group of propriospinal neurons in cats]. Responses of propriospinal interneurons localized in the ventromedial regions of the cat lumbar cord to the reticulospinal tract stimulation were studied. Monosynaptic excitatory action usually accompanied by di- and polysynaptic components was found in most units. Strong single stimuli were able to evoke discharges only in some cells, while temporal summation was necessary in many others. Excitation of neurons was followed by a short postactivation inhibition limiting the maximal discharge frequency."}
{"id": "PMID:193060", "title": "[Extracranial metastasis of primary brain tumours].", "content": "This study deals with the visceral metastasis of glioblastomas, ependymomas, oligodendrogliomas and medulloblastomas. Taking a sery fo four cases in the medical literature out of one hundred and fifteen cases published since 1961 and selected according the WEISS criterias, allows to indicate the delay in apparition of these metastasis as well as their elective localisation depending on the anatomopathological type of the original cerebral tumor. It does not give any precise indication to why these visceral metastasis appear. It seems to be very likely that the apparition of these secondary tumors is due to the failure of the shole defence systems of the body, favoured by the relative long survical of these patients and the surgical opening of the brain envelops.", "contents": "[Extracranial metastasis of primary brain tumours]. This study deals with the visceral metastasis of glioblastomas, ependymomas, oligodendrogliomas and medulloblastomas. Taking a sery fo four cases in the medical literature out of one hundred and fifteen cases published since 1961 and selected according the WEISS criterias, allows to indicate the delay in apparition of these metastasis as well as their elective localisation depending on the anatomopathological type of the original cerebral tumor. It does not give any precise indication to why these visceral metastasis appear. It seems to be very likely that the apparition of these secondary tumors is due to the failure of the shole defence systems of the body, favoured by the relative long survical of these patients and the surgical opening of the brain envelops."}
{"id": "PMID:193064", "title": "Cyclic 3'5'-adenosine monophosphate in the hypothalamo-neurohypophysial system of normal, NaCl-treated and lactating rats.", "content": "The presence and production of cyclic 3', 5'-adenosine monophosphate (cAMP) were investigated in the hypothalamus and neural lobe of the rat. Theophylline (concentrations from 10(-3) to 8 X 10(-3) M) increased the in vitro content of cAMP in the isolated neural lobe and in hypothalamic tissue samples containing supraoptic (SO) or paraventricular (PV) nuclei. Acetylcholine (ACH; 10(-2) and 10(-4) M) or carbachol (10(-4) M) did not increase cAMP content in the isolated neural lobe. Small increases were apparent (p less than 0.05, t-test for paired samples) in the hypothalamus. The amounts of cAMP were significantly higher in isolated neural lobes but not in hypothalami of NaCl-treated or lactating as compared to control rats. Presence of cAMP in the neural lobe and activation of adenylate cyclase under stimulated hormone release conditions indicate a possible involvement of cAMP in the process of neurohypophysial hormone secretion.", "contents": "Cyclic 3'5'-adenosine monophosphate in the hypothalamo-neurohypophysial system of normal, NaCl-treated and lactating rats. The presence and production of cyclic 3', 5'-adenosine monophosphate (cAMP) were investigated in the hypothalamus and neural lobe of the rat. Theophylline (concentrations from 10(-3) to 8 X 10(-3) M) increased the in vitro content of cAMP in the isolated neural lobe and in hypothalamic tissue samples containing supraoptic (SO) or paraventricular (PV) nuclei. Acetylcholine (ACH; 10(-2) and 10(-4) M) or carbachol (10(-4) M) did not increase cAMP content in the isolated neural lobe. Small increases were apparent (p less than 0.05, t-test for paired samples) in the hypothalamus. The amounts of cAMP were significantly higher in isolated neural lobes but not in hypothalami of NaCl-treated or lactating as compared to control rats. Presence of cAMP in the neural lobe and activation of adenylate cyclase under stimulated hormone release conditions indicate a possible involvement of cAMP in the process of neurohypophysial hormone secretion."}
{"id": "PMID:193065", "title": "Rat hypothalamic corticotropin-releasing factor (CRF) content remains constant despite marked acute or chronic changes in ACTH secretion.", "content": "Hypothalamic corticotropin-releasing factor (CRF) activity was only slightly increased by 1 min ether stress and was unaltered by 2.5-10 min ether stress, 15-day adrenalectomy, 11-day hypophysectomy or 3-day dexamethasone treatment. There was a slight tendency for the hypothalamic CRF activity to be higher in the p.m. than in the a.m. Basal hypothalamic deafferentation did not significantly affect hypothalamic CRF content in the a.m. or p.m. compared to intact controls. We conclude that hypothalamic CRF content maintains relative constancy under conditions of marked acute or chronic stimulation or suppression of ACTH secretion.", "contents": "Rat hypothalamic corticotropin-releasing factor (CRF) content remains constant despite marked acute or chronic changes in ACTH secretion. Hypothalamic corticotropin-releasing factor (CRF) activity was only slightly increased by 1 min ether stress and was unaltered by 2.5-10 min ether stress, 15-day adrenalectomy, 11-day hypophysectomy or 3-day dexamethasone treatment. There was a slight tendency for the hypothalamic CRF activity to be higher in the p.m. than in the a.m. Basal hypothalamic deafferentation did not significantly affect hypothalamic CRF content in the a.m. or p.m. compared to intact controls. We conclude that hypothalamic CRF content maintains relative constancy under conditions of marked acute or chronic stimulation or suppression of ACTH secretion."}
{"id": "PMID:193061", "title": "[Sleep characteristics during 1st night in laboratory].", "content": "Three goups, each composed of five individuals were investigated: students, patients and controls aged 20--45 years. The characteristic features of the first sleep in the laboratory were compared with the sleep during experimental pre-examination stress in students and preoperative stress in patients. It was found that the first sleep in the laboratory had the same features as the sleep in experimental stress. The process of adaptation to the conditions of sleep in the laboratory during the 2nd and 3rd night was studied. In the case of patients no adaptation was observed during three successive nights.", "contents": "[Sleep characteristics during 1st night in laboratory]. Three goups, each composed of five individuals were investigated: students, patients and controls aged 20--45 years. The characteristic features of the first sleep in the laboratory were compared with the sleep during experimental pre-examination stress in students and preoperative stress in patients. It was found that the first sleep in the laboratory had the same features as the sleep in experimental stress. The process of adaptation to the conditions of sleep in the laboratory during the 2nd and 3rd night was studied. In the case of patients no adaptation was observed during three successive nights."}
{"id": "PMID:193062", "title": "[Cytochemical studies of peripheral white blood cells in Wilson's disease].", "content": "Using cytochemical methods the authors studied the activity of certain lysosomal enzymes and cytochrome oxidase in peripheral blood leucoytes in 22 patients with Wilson's disease. The control group comprised 50 healthy blood donors. It was found that the activity of acid phosphatase in the lymphocytes of patients was higher than in controls, the mean indices being respectively 90.50 +/- 8.95 and 60.38 +/- 3.95. The activity of beta-glucuronidase was found to be lower in the lymphocytes of patients, the mean value was 25.10 +/- 8.59 in patients and 64.91 +/- 5.78 in controls. The activity of cytochrome oxidase was lower in the granulocytes of patients with Wilson's disease than in controls, the mean values being 54.5 +/- 12.14 and 156 +/- 15.41 respectively. The activity of acid phosphatase in granulocytes as well as that of non-specific esterase in lymphocytes was similar in both groups. Decreased antigen degradation in Wilson's disease may be due not only to liver cirrhosis but also to disturbances in the metabolism of white blood cells, including, among others, decreased activity of cytochrome oxidase. The rise of the activity of acid phosphatase and reduced activity of beta-glucuronidase indicate chronic antigenic stimulation of lymphoid system.", "contents": "[Cytochemical studies of peripheral white blood cells in Wilson's disease]. Using cytochemical methods the authors studied the activity of certain lysosomal enzymes and cytochrome oxidase in peripheral blood leucoytes in 22 patients with Wilson's disease. The control group comprised 50 healthy blood donors. It was found that the activity of acid phosphatase in the lymphocytes of patients was higher than in controls, the mean indices being respectively 90.50 +/- 8.95 and 60.38 +/- 3.95. The activity of beta-glucuronidase was found to be lower in the lymphocytes of patients, the mean value was 25.10 +/- 8.59 in patients and 64.91 +/- 5.78 in controls. The activity of cytochrome oxidase was lower in the granulocytes of patients with Wilson's disease than in controls, the mean values being 54.5 +/- 12.14 and 156 +/- 15.41 respectively. The activity of acid phosphatase in granulocytes as well as that of non-specific esterase in lymphocytes was similar in both groups. Decreased antigen degradation in Wilson's disease may be due not only to liver cirrhosis but also to disturbances in the metabolism of white blood cells, including, among others, decreased activity of cytochrome oxidase. The rise of the activity of acid phosphatase and reduced activity of beta-glucuronidase indicate chronic antigenic stimulation of lymphoid system."}
{"id": "PMID:193063", "title": "[Case of spinal cord injury at the site of its junction with the medulla].", "content": "The authors describe a case of spinal cord injury close to the site of its junction with the medulla. The injury was caused by the sharp end of joiner file. Following the injury a neurological syndrome developed indicating selective direct injury to the pyramidal tract in the left lateral funiculi of the cord and to the pathways of deep sensation on the left side, as well a transient injury to the pathways of superficial sensation on the side.", "contents": "[Case of spinal cord injury at the site of its junction with the medulla]. The authors describe a case of spinal cord injury close to the site of its junction with the medulla. The injury was caused by the sharp end of joiner file. Following the injury a neurological syndrome developed indicating selective direct injury to the pyramidal tract in the left lateral funiculi of the cord and to the pathways of deep sensation on the left side, as well a transient injury to the pathways of superficial sensation on the side."}
{"id": "PMID:193069", "title": "[Osteopetrosis (Albers-Schoenberg disease). III. Current nosographic aspects and relations to other condensing osteopathies].", "content": "A malignant paediatric variety and an adult variety of Albers-Sch\u00f6nberg disease are normally distinguished. On the basis of recent findings and personal observation it would appear advisable to accept two different courses of Albers-Sch\u00f6nberg disease in adults: one resembling the malignant infant form and the other with slow, practically asymptomatic (apart, obviously, from the skeletal lesions) course allowing for prolonged survival. This classification is of considerable practical importance for prognosis and therapeutic purposes. Other hereditary-familial and constitutional condensing osteopathy pictures exist that present radiological stigmata similar to those seen in Albers-Sch\u00f6nberg disease. The interest of the relations between A-S disease and certain of these condensing osteopathic conditions is obvious.", "contents": "[Osteopetrosis (Albers-Schoenberg disease). III. Current nosographic aspects and relations to other condensing osteopathies]. A malignant paediatric variety and an adult variety of Albers-Sch\u00f6nberg disease are normally distinguished. On the basis of recent findings and personal observation it would appear advisable to accept two different courses of Albers-Sch\u00f6nberg disease in adults: one resembling the malignant infant form and the other with slow, practically asymptomatic (apart, obviously, from the skeletal lesions) course allowing for prolonged survival. This classification is of considerable practical importance for prognosis and therapeutic purposes. Other hereditary-familial and constitutional condensing osteopathy pictures exist that present radiological stigmata similar to those seen in Albers-Sch\u00f6nberg disease. The interest of the relations between A-S disease and certain of these condensing osteopathic conditions is obvious."}
{"id": "PMID:193070", "title": "[Analysis of surgical treatment of 592 cases of cancer of the stomach].", "content": "A series of 592 cases of gastric carcinoma operated on between January 1960 and December 1974 at the S. Croce Hospital at Cuneo is reported. The following observations were made: greater frequency in males (68.25%). The following localizations: cardiac portion 31 cases; fundus 20; body 93 and antropyloric 249. Cancer ulcer in 5.06% of cases. Cancer on the gastric stump in ulcer resections in two cases. The following operations were performed: Gastric resection in 325 cases: operative mortality (O.M.) 5%; 5-year survival: 18%. Total gastrectomy in 38 cases: O.M. 13.1%; 2-year survival: 21%, 5-year survival 5.2%. E.A.G. in 61 cases; O.M. 17.8%; survival: 6 months; maximum 26 months. Gastrostomy in 16 cases; Expl. laparotomy in 150 cases. Survival was only a few months in these two latter groups. Out of all operations 5-year survival was 6.7% and 27.4% in so-called curative interventions. In principle, gastric resection is still considered to be the most valid approach.", "contents": "[Analysis of surgical treatment of 592 cases of cancer of the stomach]. A series of 592 cases of gastric carcinoma operated on between January 1960 and December 1974 at the S. Croce Hospital at Cuneo is reported. The following observations were made: greater frequency in males (68.25%). The following localizations: cardiac portion 31 cases; fundus 20; body 93 and antropyloric 249. Cancer ulcer in 5.06% of cases. Cancer on the gastric stump in ulcer resections in two cases. The following operations were performed: Gastric resection in 325 cases: operative mortality (O.M.) 5%; 5-year survival: 18%. Total gastrectomy in 38 cases: O.M. 13.1%; 2-year survival: 21%, 5-year survival 5.2%. E.A.G. in 61 cases; O.M. 17.8%; survival: 6 months; maximum 26 months. Gastrostomy in 16 cases; Expl. laparotomy in 150 cases. Survival was only a few months in these two latter groups. Out of all operations 5-year survival was 6.7% and 27.4% in so-called curative interventions. In principle, gastric resection is still considered to be the most valid approach."}
{"id": "PMID:193072", "title": "Estrogens and endometrial carcinoma.", "content": "A group of 205 women with endometrial carcinoma was matched for age, parity, and year of operation with a group of 205 women who had had hysterectomies for benign disease. In the former group, 32 patients had used conjugated estrogens, while in the latter group 12 had used this hormone, yielding a relative risk of 3.1 (P = 0.0008). Users of other forms of systemic estrogens showed similar elevations in relative risk. Relative risk was related to duration of use, progressing from no evidence of risk among those using the hormone for less than 5 years to an 11.5-fold greater risk for those using it for 10 years or more. Risk was also related to the strength of the medication. The relative risk for users of the 1.25-mg tablets was 12.7 as compared to a two- to fourfold greater risk among users of lesser strength tablets.", "contents": "Estrogens and endometrial carcinoma. A group of 205 women with endometrial carcinoma was matched for age, parity, and year of operation with a group of 205 women who had had hysterectomies for benign disease. In the former group, 32 patients had used conjugated estrogens, while in the latter group 12 had used this hormone, yielding a relative risk of 3.1 (P = 0.0008). Users of other forms of systemic estrogens showed similar elevations in relative risk. Relative risk was related to duration of use, progressing from no evidence of risk among those using the hormone for less than 5 years to an 11.5-fold greater risk for those using it for 10 years or more. Risk was also related to the strength of the medication. The relative risk for users of the 1.25-mg tablets was 12.7 as compared to a two- to fourfold greater risk among users of lesser strength tablets."}
{"id": "PMID:193073", "title": "Endometrial carcinoma and oral contraceptive agents.", "content": "Six patients who took oral contraceptive agents for 5 to 18 years developed endometrial neoplasia. Endometrial adenocarcinoma occurred in 4 of these patients and severe adenomatous hyperplasia occured in 2. Five of the 6 patients took sequential agents; 1 patient used a combined agent. An additional patient who took Premarin and Provera sequentially developed adenocarcinoma of the endometrium. Eighteen cases of endometrial adenocarcinoma and 7 cases of adenomatous hyperplasia in patients with long-term sequential oral contraceptive use have previously been reported by others. Progestogens may not be completely protective against the endometrial cancer-causing potential of the estrogens, especially in the sequential regimens.", "contents": "Endometrial carcinoma and oral contraceptive agents. Six patients who took oral contraceptive agents for 5 to 18 years developed endometrial neoplasia. Endometrial adenocarcinoma occurred in 4 of these patients and severe adenomatous hyperplasia occured in 2. Five of the 6 patients took sequential agents; 1 patient used a combined agent. An additional patient who took Premarin and Provera sequentially developed adenocarcinoma of the endometrium. Eighteen cases of endometrial adenocarcinoma and 7 cases of adenomatous hyperplasia in patients with long-term sequential oral contraceptive use have previously been reported by others. Progestogens may not be completely protective against the endometrial cancer-causing potential of the estrogens, especially in the sequential regimens."}
{"id": "PMID:193075", "title": "[Keractoconjunctivitis caused by type 10 adenovirus].", "content": "4 cases in which type 10 adenovirus was isolated are described in connection with a new form of viral keratoconjunctivitis. The predominant symptoms, after disappearance of the benign-type conjunctivitis signs by the 5th day, are those of edema of the lids, chemosis, multiple corneal erosions and folds in Descemet's membrane, reaching their maxima by the 15th day. The course of the disease is of roughly 30 days.", "contents": "[Keractoconjunctivitis caused by type 10 adenovirus]. 4 cases in which type 10 adenovirus was isolated are described in connection with a new form of viral keratoconjunctivitis. The predominant symptoms, after disappearance of the benign-type conjunctivitis signs by the 5th day, are those of edema of the lids, chemosis, multiple corneal erosions and folds in Descemet's membrane, reaching their maxima by the 15th day. The course of the disease is of roughly 30 days."}
{"id": "PMID:193077", "title": "[HLA-SD-antigens in cervix cancer and recurrent herpes genitalis patients (author's transl)].", "content": "The frequency of 36 HLA-SD antigens were investigated in 42 patients with cervix cancer, 36 female patients with recurrent Herpes genitalis and 450 healthy controls. The only significant difference between the 3 groups was an increase in the frequency of BW 15 in the cervix cancer patients. The patients with recurrent Herpes genitalis--who were sero-epidemiologically determined to have a higher risk of developing a cervix carcinoma-showed no significant difference in their HLA-SD antigen frequencies in comparison with the controls and the cervix carcinoma patients.", "contents": "[HLA-SD-antigens in cervix cancer and recurrent herpes genitalis patients (author's transl)]. The frequency of 36 HLA-SD antigens were investigated in 42 patients with cervix cancer, 36 female patients with recurrent Herpes genitalis and 450 healthy controls. The only significant difference between the 3 groups was an increase in the frequency of BW 15 in the cervix cancer patients. The patients with recurrent Herpes genitalis--who were sero-epidemiologically determined to have a higher risk of developing a cervix carcinoma-showed no significant difference in their HLA-SD antigen frequencies in comparison with the controls and the cervix carcinoma patients."}
{"id": "PMID:193078", "title": "[On the histogenesis of uterine mixed tumors (author's transl)].", "content": "Heterologous tumors of the uterus are commonly designated as M\u00fcllerian mixed tumors. Their origin is attributed to dispersed embryogenic isles of M\u00fcllerian duct. The always high age of the afflicted woman plus the localization in post-climacteric polyps, speak against this assumption. Five personal observations have motivated the more intensive occupation with the histiogenesis of these cases. This has led to the conclusion that these mixed tissue formations do not come from dispersed cell isles, but that the multipotency of proliferated cells has only appeared in later age in connection with a metaplasia.", "contents": "[On the histogenesis of uterine mixed tumors (author's transl)]. Heterologous tumors of the uterus are commonly designated as M\u00fcllerian mixed tumors. Their origin is attributed to dispersed embryogenic isles of M\u00fcllerian duct. The always high age of the afflicted woman plus the localization in post-climacteric polyps, speak against this assumption. Five personal observations have motivated the more intensive occupation with the histiogenesis of these cases. This has led to the conclusion that these mixed tissue formations do not come from dispersed cell isles, but that the multipotency of proliferated cells has only appeared in later age in connection with a metaplasia."}
{"id": "PMID:193079", "title": "The tumor enhancing property of herpes simplex virus type-2 (HSV-2).", "content": "The s.c. infection of DBF-1 mice with HSV-2 has a tumor enhancing effect on simultaneously i.m. implanted MCA-induced syngeneic spindle cell sarcoma. Thus with the dosage used here, the first palpable tumors appeared on day 6 in the virus treated group as compared to day 9 p.i. in the sham treated batch. Further, more tumors were formed: 75% among the infected and 40% among the sham injected. The tumor yield could be modulated: no difference between the 2 groups was found when the tumor cell dose was increased sufficiently to advance the first appearance of tumors to less than 6 days. The same result was obtained when the neoplastic cells were implanted 3 days ahead of injection of the virus. When the dose of the cells was decreased, no tumors were found in the sham treated batch, whereas there were some in the infected group. Previous in vitro mixing of the neoplastic cells with virus completely prevented tumor formation, probably due to their lysis by the virus. In fact, in tissue cultures, MCA cells become lytically infected with HSV-2. It is speculated that a similar situation occurs in acutely ill mice which die before the 13th day p.i., i.e., the tumor cells are destroyed by the virus. In fact, those animals, as a rule are free of neoplasmas. Thus it appears that an acute HSV-2 infection prevents MCA sarcoma whereas a latent infection promotes its growth. The possible reasons for this tumor enhancement caused by HSV-2 infection are discussed.", "contents": "The tumor enhancing property of herpes simplex virus type-2 (HSV-2). The s.c. infection of DBF-1 mice with HSV-2 has a tumor enhancing effect on simultaneously i.m. implanted MCA-induced syngeneic spindle cell sarcoma. Thus with the dosage used here, the first palpable tumors appeared on day 6 in the virus treated group as compared to day 9 p.i. in the sham treated batch. Further, more tumors were formed: 75% among the infected and 40% among the sham injected. The tumor yield could be modulated: no difference between the 2 groups was found when the tumor cell dose was increased sufficiently to advance the first appearance of tumors to less than 6 days. The same result was obtained when the neoplastic cells were implanted 3 days ahead of injection of the virus. When the dose of the cells was decreased, no tumors were found in the sham treated batch, whereas there were some in the infected group. Previous in vitro mixing of the neoplastic cells with virus completely prevented tumor formation, probably due to their lysis by the virus. In fact, in tissue cultures, MCA cells become lytically infected with HSV-2. It is speculated that a similar situation occurs in acutely ill mice which die before the 13th day p.i., i.e., the tumor cells are destroyed by the virus. In fact, those animals, as a rule are free of neoplasmas. Thus it appears that an acute HSV-2 infection prevents MCA sarcoma whereas a latent infection promotes its growth. The possible reasons for this tumor enhancement caused by HSV-2 infection are discussed."}
{"id": "PMID:193080", "title": "Neoplasms of the nasopharynx in children.", "content": "Neoplasms of the nasopharynx are rare in children, but they threaten the child's life when they do occur. The nasopharynx tends to harbor dysontogenetic neoplasms. After classification into benign and malignant groups, nasopharyngeal neoplasms in children can be further characterized according to the age of the patients in which the clinical manifestations usually appear. Dermoids and teratomas are the most frequently encountered neoplasms of the nasopharynx in infants and may produce airway obstruction and dysphagia. Among the benign tumors of the nasopharynx in children, the juvenile angiofibroma deserves the most attention. With the onset in puberty, these neoplasms may cause recurrent massive bleeding and orbital and intracranial complications. Evaluation of the extent of the neoplasm and the source of the blood supply has been improved with bilateral selective internal and external carotid angiography. Intracranial and orbital invasion is regarded as an indication for radiotherapy. Surgery has been made somewhat safer by preoperative estrogen therapy and angiographic embolization of the major arterial supply. Patients with squamous cell carcinoma of the nasopharynx have immunologic similarities to patients with Burkitt's lymphomia and infectious mononucleosis; The etiologic role of the Epstein-Barr virus is considered. The parts played by radiation therapy, surgery, chemotherapy, and cryosurgery in the treatment of children with carcinoma of the nasopharynx are discussed. The value of radical neck dissection after radiation therapy is critically reviewed. The prognosis in patients with carcinoma of the nasopharynx is better in females than in males and better in children than in adults.", "contents": "Neoplasms of the nasopharynx in children. Neoplasms of the nasopharynx are rare in children, but they threaten the child's life when they do occur. The nasopharynx tends to harbor dysontogenetic neoplasms. After classification into benign and malignant groups, nasopharyngeal neoplasms in children can be further characterized according to the age of the patients in which the clinical manifestations usually appear. Dermoids and teratomas are the most frequently encountered neoplasms of the nasopharynx in infants and may produce airway obstruction and dysphagia. Among the benign tumors of the nasopharynx in children, the juvenile angiofibroma deserves the most attention. With the onset in puberty, these neoplasms may cause recurrent massive bleeding and orbital and intracranial complications. Evaluation of the extent of the neoplasm and the source of the blood supply has been improved with bilateral selective internal and external carotid angiography. Intracranial and orbital invasion is regarded as an indication for radiotherapy. Surgery has been made somewhat safer by preoperative estrogen therapy and angiographic embolization of the major arterial supply. Patients with squamous cell carcinoma of the nasopharynx have immunologic similarities to patients with Burkitt's lymphomia and infectious mononucleosis; The etiologic role of the Epstein-Barr virus is considered. The parts played by radiation therapy, surgery, chemotherapy, and cryosurgery in the treatment of children with carcinoma of the nasopharynx are discussed. The value of radical neck dissection after radiation therapy is critically reviewed. The prognosis in patients with carcinoma of the nasopharynx is better in females than in males and better in children than in adults."}
{"id": "PMID:193082", "title": "[Tubular and intestinal phosphate transport in vitamin D-resistant (hypophosphatemic) rickets (author's transl)].", "content": "Renal clearance and intestinal absorption studies were performed to investigate the renal and intestinal handling of phosphate under various conditions in two female patients with VDRR. The two types of transepithelial phosphate transport in the renal proximal tubule and intestinal mucosa are discussed. The defective parathormone sensible transport mechanism is slightly depressed under the influence of parathormone and activated after treatment of vitamin D in one patient, in the other no further inhibition by PTH could be observed. Electrolyte excretion in urine remains stable during treatment with vitamin D 3. Therapy consists of administration of oral phosphate and of pharmacologic doses of vitamin D.", "contents": "[Tubular and intestinal phosphate transport in vitamin D-resistant (hypophosphatemic) rickets (author's transl)]. Renal clearance and intestinal absorption studies were performed to investigate the renal and intestinal handling of phosphate under various conditions in two female patients with VDRR. The two types of transepithelial phosphate transport in the renal proximal tubule and intestinal mucosa are discussed. The defective parathormone sensible transport mechanism is slightly depressed under the influence of parathormone and activated after treatment of vitamin D in one patient, in the other no further inhibition by PTH could be observed. Electrolyte excretion in urine remains stable during treatment with vitamin D 3. Therapy consists of administration of oral phosphate and of pharmacologic doses of vitamin D."}
{"id": "PMID:193085", "title": "Cyclic nucleotide phosphodiesterase activities of the fetal and mature human cerebral cortex.", "content": "Phosphodiesterase activities were examined in the supernatant and pellet fractions of a 30,000 X g preparation of brain tissues from human fetuses and young adults. Differences in total activity and distribution of the high and low Km activity enzymes for adenosine and guanosine 3',5'-monophosphate (cyclic AMP and cyclic GMP, respectively) were found. The mature cortex had 10 times more activity than the fetal brain for cyclic AMP hydrolysis and 15-20 times more activity for cyclic GMP hydrolysis. In the fetus, more activity for both nucleotides at both high and low concentrations is associated with the supernatant fraction. With maturity, a shift in localization of high Km activity for cyclic GMP and low Km activities for both nucleotides to the particulate fraction is observed. Michaelis constants for both mature and immature brains are similar. The Km values for cyclic AMP are 10(-4) and 10(-5) M and 10(-4) and 10(-6) M for cyclic GMP. The Vmax values differed by a factor of 10 between the high Km and the low Km forms for each substrate. Differences were observed between the fetus and the adult when the hydrolysis of one nucleotide was measured in the presence of varying amounts of the other nucleotide. Low concentrations of either nucleotide stimulated the hydrolysis of low concentrations of the other in the adult whereas, in the fetus, low concentrations of cyclic AMP inhibited cyclic GMP hydrolysis. At higher concentrations of either nucleotide, the addition of the other over a wide range of concentrations resulted in inhibition which was exaggerated in the fetus.", "contents": "Cyclic nucleotide phosphodiesterase activities of the fetal and mature human cerebral cortex. Phosphodiesterase activities were examined in the supernatant and pellet fractions of a 30,000 X g preparation of brain tissues from human fetuses and young adults. Differences in total activity and distribution of the high and low Km activity enzymes for adenosine and guanosine 3',5'-monophosphate (cyclic AMP and cyclic GMP, respectively) were found. The mature cortex had 10 times more activity than the fetal brain for cyclic AMP hydrolysis and 15-20 times more activity for cyclic GMP hydrolysis. In the fetus, more activity for both nucleotides at both high and low concentrations is associated with the supernatant fraction. With maturity, a shift in localization of high Km activity for cyclic GMP and low Km activities for both nucleotides to the particulate fraction is observed. Michaelis constants for both mature and immature brains are similar. The Km values for cyclic AMP are 10(-4) and 10(-5) M and 10(-4) and 10(-6) M for cyclic GMP. The Vmax values differed by a factor of 10 between the high Km and the low Km forms for each substrate. Differences were observed between the fetus and the adult when the hydrolysis of one nucleotide was measured in the presence of varying amounts of the other nucleotide. Low concentrations of either nucleotide stimulated the hydrolysis of low concentrations of the other in the adult whereas, in the fetus, low concentrations of cyclic AMP inhibited cyclic GMP hydrolysis. At higher concentrations of either nucleotide, the addition of the other over a wide range of concentrations resulted in inhibition which was exaggerated in the fetus."}
{"id": "PMID:193086", "title": "Auditory and visual defects resulting from symptomatic and subclinical congenital cytomegaloviral and toxoplasma infections.", "content": "Sensorineural hearing loss was present in ten of 59 (17%) patients with congenital cytomegalovirus (CMV) infection (three of eight born with symptomatic and seven of 51 born with subclinical infection). The defect was bilateral in eight, moderate to profound in eight, and of progressive nature in two. Hearing loss did not occur in 21 patients with natal CMV infection nor in seven of 12 patients with congenital toxoplasmosis. Histopathologic and immunofluorescent studies of the inner ear in two of three neonates who died with severe infection revealed that viral antigens were widely distributed in cochlear structures. Eye pathology was associated only with congenital Toxoplasma (nine of 12) and CMV (seven of 43) infections. Visual impairments were more prominent and severe in those born with symptomatic infections, exclusively so with CMV. However, ocular defects, in particular chorioretinitis, developed after birth in five of eight patients born with asymptomatic congenital toxoplasmosis. These data firmly establish clinically inapparent congenital CMV infection as a major public health problem and confirm the fact that congenital toxoplasmosis may be associated with late-appearing, debilitating chorioretinitis.", "contents": "Auditory and visual defects resulting from symptomatic and subclinical congenital cytomegaloviral and toxoplasma infections. Sensorineural hearing loss was present in ten of 59 (17%) patients with congenital cytomegalovirus (CMV) infection (three of eight born with symptomatic and seven of 51 born with subclinical infection). The defect was bilateral in eight, moderate to profound in eight, and of progressive nature in two. Hearing loss did not occur in 21 patients with natal CMV infection nor in seven of 12 patients with congenital toxoplasmosis. Histopathologic and immunofluorescent studies of the inner ear in two of three neonates who died with severe infection revealed that viral antigens were widely distributed in cochlear structures. Eye pathology was associated only with congenital Toxoplasma (nine of 12) and CMV (seven of 43) infections. Visual impairments were more prominent and severe in those born with symptomatic infections, exclusively so with CMV. However, ocular defects, in particular chorioretinitis, developed after birth in five of eight patients born with asymptomatic congenital toxoplasmosis. These data firmly establish clinically inapparent congenital CMV infection as a major public health problem and confirm the fact that congenital toxoplasmosis may be associated with late-appearing, debilitating chorioretinitis."}
{"id": "PMID:193087", "title": "Dose-response curve of glutamate applied by superfusion to crayfish muscle synapses.", "content": "Single muscle fibers were space clamped to a membrane potential of -75 to -80 mV, and the synaptic currents elicited by L-glutamate (gEPSCs) were recorded. The bathing solutions flowing across the fibers at high speed could be switched rapidly and repeatedly through valves actuated by solenoids. Glutamate solutions were applied for periods of 7 s or 1 s, and the responses to repeated applications were averaged. For glutamate concentrations of 10-50 mumol/l, applied for 7 s, the gEPSCs reached a steady state. In this concentration range the amplitude of the gEPSC rose steeply proportional to the power n=2.5 to n=6 (average of 12 experiments n=4.0) of the glutamate concentration. At higher concentrations, after rising for a few seconds the gEPSC was reduced by desensitization. At 500 mumol/l glutamate complete desensitization was reached with an approximate time constant of less than 1 s. The glutamate concentration that elicited a half maximum gEPSC was K=70 mumol/l. If glutamate was superfused only for 1 s, similar dose-response curves were observed. In these experiments n was between 4 and 6. The results obtained by superfusion agree quantitatively with those published for electrophoretic applications.", "contents": "Dose-response curve of glutamate applied by superfusion to crayfish muscle synapses. Single muscle fibers were space clamped to a membrane potential of -75 to -80 mV, and the synaptic currents elicited by L-glutamate (gEPSCs) were recorded. The bathing solutions flowing across the fibers at high speed could be switched rapidly and repeatedly through valves actuated by solenoids. Glutamate solutions were applied for periods of 7 s or 1 s, and the responses to repeated applications were averaged. For glutamate concentrations of 10-50 mumol/l, applied for 7 s, the gEPSCs reached a steady state. In this concentration range the amplitude of the gEPSC rose steeply proportional to the power n=2.5 to n=6 (average of 12 experiments n=4.0) of the glutamate concentration. At higher concentrations, after rising for a few seconds the gEPSC was reduced by desensitization. At 500 mumol/l glutamate complete desensitization was reached with an approximate time constant of less than 1 s. The glutamate concentration that elicited a half maximum gEPSC was K=70 mumol/l. If glutamate was superfused only for 1 s, similar dose-response curves were observed. In these experiments n was between 4 and 6. The results obtained by superfusion agree quantitatively with those published for electrophoretic applications."}
{"id": "PMID:193088", "title": "[Changes in plasma level of corticotropin after intravenous injection of metyrapone. Value of this test in pituitary pathology].", "content": "The Metyrapone was given, the morning, in perfusion intravenous of saline serum over 2 hours. A.C.T.H. levels were determined before and at 2, 4, 8 and 24 hours. Sixteen normal subjects adults served on controls with 1 g of Metyrapone. Sixteen other normal subjects with 2 g of Metyrapone are best responses. With this maximum dose 2 g were studied nine hypophysal adenomas with three low responses, three normal and three high responses; thirteen hypophysectomised subjects with very low peak value at 4 hours, and only two responses higher than the controls, five Cushing's syndromes with variable responses. The I.V. Metyrapone test seems to offer several advantages: it eliminates the questions about gastro-intestinal absorption of Metyrapone (oral) and the difficulties of urine collection. With the A.C.T.H. dosage on 4 hours, this is a rapid test able to put in combination other hypophysal tests.", "contents": "[Changes in plasma level of corticotropin after intravenous injection of metyrapone. Value of this test in pituitary pathology]. The Metyrapone was given, the morning, in perfusion intravenous of saline serum over 2 hours. A.C.T.H. levels were determined before and at 2, 4, 8 and 24 hours. Sixteen normal subjects adults served on controls with 1 g of Metyrapone. Sixteen other normal subjects with 2 g of Metyrapone are best responses. With this maximum dose 2 g were studied nine hypophysal adenomas with three low responses, three normal and three high responses; thirteen hypophysectomised subjects with very low peak value at 4 hours, and only two responses higher than the controls, five Cushing's syndromes with variable responses. The I.V. Metyrapone test seems to offer several advantages: it eliminates the questions about gastro-intestinal absorption of Metyrapone (oral) and the difficulties of urine collection. With the A.C.T.H. dosage on 4 hours, this is a rapid test able to put in combination other hypophysal tests."}
{"id": "PMID:193089", "title": "[Thecal tumors of the ovary. 14 cases].", "content": "Out of 524 tumours of the ovary seen over a 20 year period, the diagnosis was that of a thecal tumour in 14 cases. In addition to the symptoms common to all ovarian tumours, in 7 cases there was metrorrhagia, including 4 post-menopausal. Vaginal cytology after the menopause was abnormally young in 6 cases. In 7 cases out of 13 the endometrium was hyperplasic. In only 5 cases were urinary oestrogen levels increased. At operation, the tumour was bilateral in 3 cases and ascites was present in 4. Histological findings were as follows: 6 thecomas, 4 fibro-thecomas, 1 luteinised thecal tumour, 3 tumours with granular cells and 1 case associated with a Brenner tumour. Two of these \"mixed tumours\" were malignant, with a fatal outcome. All the others were cured by operation. In young women in whom conservative procedures were used there were 4 subsequent pregnancies. The following questions were posed: The coexistence of ascites with tumours totally free of secretory cells (3 cases); The existence in true thecal tumours of signs of hyperoestrogenism (5 out of 6) whilst fibro-thecomas are not associated with any abnormal production of oestrogen.", "contents": "[Thecal tumors of the ovary. 14 cases]. Out of 524 tumours of the ovary seen over a 20 year period, the diagnosis was that of a thecal tumour in 14 cases. In addition to the symptoms common to all ovarian tumours, in 7 cases there was metrorrhagia, including 4 post-menopausal. Vaginal cytology after the menopause was abnormally young in 6 cases. In 7 cases out of 13 the endometrium was hyperplasic. In only 5 cases were urinary oestrogen levels increased. At operation, the tumour was bilateral in 3 cases and ascites was present in 4. Histological findings were as follows: 6 thecomas, 4 fibro-thecomas, 1 luteinised thecal tumour, 3 tumours with granular cells and 1 case associated with a Brenner tumour. Two of these \"mixed tumours\" were malignant, with a fatal outcome. All the others were cured by operation. In young women in whom conservative procedures were used there were 4 subsequent pregnancies. The following questions were posed: The coexistence of ascites with tumours totally free of secretory cells (3 cases); The existence in true thecal tumours of signs of hyperoestrogenism (5 out of 6) whilst fibro-thecomas are not associated with any abnormal production of oestrogen."}
{"id": "PMID:193094", "title": "Hematologic and oncologic implications of alcoholism.", "content": "Hematologic complications of alcoholism are common. Folic acid deficiency can lead to pancytopenia. Iron-deficiency anemia, various hemolytic states, and abnormalities in both function and number of platelets can occur. There is a great deal of interest in the adverse effects of alcohol on pyridoxine (vitamin B6) and folic acid metabolism. Malignant disease often complicates alcoholism and should always be suspected.", "contents": "Hematologic and oncologic implications of alcoholism. Hematologic complications of alcoholism are common. Folic acid deficiency can lead to pancytopenia. Iron-deficiency anemia, various hemolytic states, and abnormalities in both function and number of platelets can occur. There is a great deal of interest in the adverse effects of alcohol on pyridoxine (vitamin B6) and folic acid metabolism. Malignant disease often complicates alcoholism and should always be suspected."}
{"id": "PMID:193095", "title": "Facial nerve injury. A short review.", "content": "Despite considerable advances in technique, experience and skill, the precise place of surgery in the treatment of facial nerve injury remains uncertain. The mechanism of delayed facial palsy is not yet clear, and there is still debate about the value of tests for early evidence of denervation. Recent literature has been reviewed.", "contents": "Facial nerve injury. A short review. Despite considerable advances in technique, experience and skill, the precise place of surgery in the treatment of facial nerve injury remains uncertain. The mechanism of delayed facial palsy is not yet clear, and there is still debate about the value of tests for early evidence of denervation. Recent literature has been reviewed."}
{"id": "PMID:193092", "title": "Synthesis and some biological properties of 6-aminopenicillanic derivatives.", "content": "The properties of 33 6-aminopenicillanic derivates were described, the majority of which and particularly all 3,4-disubstituted phenyl derivatives, are new compounds. These derivatives were synthesized by three different methods consisting in treating of 6-aminopenicillanic acid (6-APA) with appropriate phenylthio -- and phenoxyalkanecarboxylic acids. The method consisting in use of aryloxyketenes is new and claimed by the patent applications. All synthesized compounds were screened for their biological activity against 21 different strains of pathogenic microorganisms of species: Staphylococcus, Sarcina, Streptococcus, Escherichia, Proteus, Klebsiella, Neisseria, Pseudomonas, Bacillus subtilis and Candida albicans. In the present paper only the most interesting results of microbiological tests and some data concerning pharmacological investigations performed on rats, were presented. Among selected compounds both substances 30 and 32 showed animals weight growth stimulating activity.", "contents": "Synthesis and some biological properties of 6-aminopenicillanic derivatives. The properties of 33 6-aminopenicillanic derivates were described, the majority of which and particularly all 3,4-disubstituted phenyl derivatives, are new compounds. These derivatives were synthesized by three different methods consisting in treating of 6-aminopenicillanic acid (6-APA) with appropriate phenylthio -- and phenoxyalkanecarboxylic acids. The method consisting in use of aryloxyketenes is new and claimed by the patent applications. All synthesized compounds were screened for their biological activity against 21 different strains of pathogenic microorganisms of species: Staphylococcus, Sarcina, Streptococcus, Escherichia, Proteus, Klebsiella, Neisseria, Pseudomonas, Bacillus subtilis and Candida albicans. In the present paper only the most interesting results of microbiological tests and some data concerning pharmacological investigations performed on rats, were presented. Among selected compounds both substances 30 and 32 showed animals weight growth stimulating activity."}
{"id": "PMID:193093", "title": "The effect of apomorphine, amantadine and dimethylaminoadamantane on the level of cyclic AMP in the rat striatum.", "content": "The content of cyclic AMP (cAMP) in the slices of rat striatum and cerebral cortex was tested after incubation with various concentrations (10(-6)--10(4) M) of dopamine (DA), apomorphine (APM), amantadine (AMD), and dimethylaminoadamatane (DMAD), and incubation with DA, AMD and DMAD in combination with KCl (43 mM) or haloperidol (HP) (10(-5) M). APM, AMD, and DMAD act synergistically with DA, elevate the c-AMP content in the striatum less than DA dose and do not affect the level c-AMP in the slices of cerebral cortex. KCl potentiated the action of DA, but inhibited that of APM, AMD, and DMAD. HP was most effective in blocking the action of DA, and blocked more weakly the action of APM AMD, DMAD, and the action of DA, APM, AMD, and DMAD in the presence of high concentration of KCl. The results indicate that APM, AMD, and DMAD, are less specific stimulants of central dopaminergic structures than DA, and that the increase of c-AMP content in the slices of rat striatum caused by APM, AMD, and DMAD is due to depolarizing action of these compounds.", "contents": "The effect of apomorphine, amantadine and dimethylaminoadamantane on the level of cyclic AMP in the rat striatum. The content of cyclic AMP (cAMP) in the slices of rat striatum and cerebral cortex was tested after incubation with various concentrations (10(-6)--10(4) M) of dopamine (DA), apomorphine (APM), amantadine (AMD), and dimethylaminoadamatane (DMAD), and incubation with DA, AMD and DMAD in combination with KCl (43 mM) or haloperidol (HP) (10(-5) M). APM, AMD, and DMAD act synergistically with DA, elevate the c-AMP content in the striatum less than DA dose and do not affect the level c-AMP in the slices of cerebral cortex. KCl potentiated the action of DA, but inhibited that of APM, AMD, and DMAD. HP was most effective in blocking the action of DA, and blocked more weakly the action of APM AMD, DMAD, and the action of DA, APM, AMD, and DMAD in the presence of high concentration of KCl. The results indicate that APM, AMD, and DMAD, are less specific stimulants of central dopaminergic structures than DA, and that the increase of c-AMP content in the slices of rat striatum caused by APM, AMD, and DMAD is due to depolarizing action of these compounds."}
{"id": "PMID:193096", "title": "Characterization of the 3' terminus of RNA isolated from vesicular stomatitis virus and from its defective interfering particles.", "content": "The 3' termini of RNA from vesicular stomatitis virus and from three widely dissimilar defective interfering particles of the virus are PypGpU-OH. The possible relevance of these findings to autointerference and to replication of vesicular stomatitis virus is discussed.", "contents": "Characterization of the 3' terminus of RNA isolated from vesicular stomatitis virus and from its defective interfering particles. The 3' termini of RNA from vesicular stomatitis virus and from three widely dissimilar defective interfering particles of the virus are PypGpU-OH. The possible relevance of these findings to autointerference and to replication of vesicular stomatitis virus is discussed."}
{"id": "PMID:193097", "title": "Mapping of sequences with 2-fold symmetry on the simian virus 40 genome: a photochemical crosslinking approach.", "content": "Sequences with 2-fold axes of symmetry have been detected and mapped on the simian virus 40 (SV40) genome by their ability to form hairpin turns in single-stranded SV40 DNA. Supercoiled SV40 DNA (SV40 I) was digested with restriction enzymes EcoRI and HpaII. The resulting linear DNA molecules with lengths of the complete SV40 genome were then denatured and photochemically reacted with 4,5',8-trimethylpsoralen (trioxsalen) at 16.0 +/- 0.5 degrees and different ionic strengths. Secondary structures on the single-stranded SV40 DNA were crosslinked and their positions analyzed by electron microscopy. There were no observable hairpin turns on the denatured SV40 DNA when it was photoreacted in 1 mM Tris-HCl/0.1 mM EDTA at pH 7.0. In 20 mM NaCl, one specific hairpin turn was detected at 0.17 +/- 0.02 map units on the map of EcoRI-digested SV40 DNA, where the 3' ends of early 19S mRNA, late 19S mRNA, and 16S mRNA of SV40 have been mapped. In 30 mM NaCl there are five more major hairpin turns besides the most stable one. The centers of four of these specific hairpin turns were mapped at 0.26 +/- 0.02, 0.68 +/- 0.03, 0.84 +/- 0.02, and 0.94 +/- 0.01 units on the map of EcoRI-digested SV40. The fifth one is at or near the unique EcoRI cleavage site on SV40 DNA. The possible functions of these sequences are discussed in terms of the nature of the promoter sites, the replication origin, the processing of RNA precursors, and regulation at the translational level.", "contents": "Mapping of sequences with 2-fold symmetry on the simian virus 40 genome: a photochemical crosslinking approach. Sequences with 2-fold axes of symmetry have been detected and mapped on the simian virus 40 (SV40) genome by their ability to form hairpin turns in single-stranded SV40 DNA. Supercoiled SV40 DNA (SV40 I) was digested with restriction enzymes EcoRI and HpaII. The resulting linear DNA molecules with lengths of the complete SV40 genome were then denatured and photochemically reacted with 4,5',8-trimethylpsoralen (trioxsalen) at 16.0 +/- 0.5 degrees and different ionic strengths. Secondary structures on the single-stranded SV40 DNA were crosslinked and their positions analyzed by electron microscopy. There were no observable hairpin turns on the denatured SV40 DNA when it was photoreacted in 1 mM Tris-HCl/0.1 mM EDTA at pH 7.0. In 20 mM NaCl, one specific hairpin turn was detected at 0.17 +/- 0.02 map units on the map of EcoRI-digested SV40 DNA, where the 3' ends of early 19S mRNA, late 19S mRNA, and 16S mRNA of SV40 have been mapped. In 30 mM NaCl there are five more major hairpin turns besides the most stable one. The centers of four of these specific hairpin turns were mapped at 0.26 +/- 0.02, 0.68 +/- 0.03, 0.84 +/- 0.02, and 0.94 +/- 0.01 units on the map of EcoRI-digested SV40. The fifth one is at or near the unique EcoRI cleavage site on SV40 DNA. The possible functions of these sequences are discussed in terms of the nature of the promoter sites, the replication origin, the processing of RNA precursors, and regulation at the translational level."}
{"id": "PMID:193098", "title": "Cellular uptake and nuclear binding of insulin in human cultured lymphocytes: evidence for potential intracellular sites of insulin action.", "content": "Human cultured lymphocytes (IM-9) were used to demonstrate that insulin can enter the intact cell and bind to the nucleus. When these lymphocytes were incubated with 125I-labeled insulin, specific cellular uptake reached a maximum within 2 min and remained at a plateau for 90 min or longer. Partially purified nuclei from such cells contained approximately 15-20% of the total cellular radioactivity. Nuclei freed of all other cellular fractions (by washing the partially purified nucleic with Triton X-100) bound approximately 7% of the total cellular radioactivity. In contrast to the rapid uptake of labeled insulin into the intact cell, specific binding to the nucleus was half-maximal after 5 min of incubation and maximal after 90 min. Both the cellular uptake and subsequent nuclear binding of labeled insulin were progressively inhibited by increasing concentrations of unlabeled hormone. Independent evidence for the nuclear binding of insulin was obtained by preparing autoradiographs of lymphocytes incubated for various times with labeled insulin. Such preparations strongly suggest that insulin binds to the plasma membrane, enters the cytosol, and then binds to the nucleus.", "contents": "Cellular uptake and nuclear binding of insulin in human cultured lymphocytes: evidence for potential intracellular sites of insulin action. Human cultured lymphocytes (IM-9) were used to demonstrate that insulin can enter the intact cell and bind to the nucleus. When these lymphocytes were incubated with 125I-labeled insulin, specific cellular uptake reached a maximum within 2 min and remained at a plateau for 90 min or longer. Partially purified nuclei from such cells contained approximately 15-20% of the total cellular radioactivity. Nuclei freed of all other cellular fractions (by washing the partially purified nucleic with Triton X-100) bound approximately 7% of the total cellular radioactivity. In contrast to the rapid uptake of labeled insulin into the intact cell, specific binding to the nucleus was half-maximal after 5 min of incubation and maximal after 90 min. Both the cellular uptake and subsequent nuclear binding of labeled insulin were progressively inhibited by increasing concentrations of unlabeled hormone. Independent evidence for the nuclear binding of insulin was obtained by preparing autoradiographs of lymphocytes incubated for various times with labeled insulin. Such preparations strongly suggest that insulin binds to the plasma membrane, enters the cytosol, and then binds to the nucleus."}
{"id": "PMID:193099", "title": "Gene cloning for the isolation of enzymes of membrane lipid synthesis: phosphatidylserine synthase overproduction in Escherichia coli.", "content": "We have screened a bank of 2000 E. coli strains carrying hybrid ColE1 plasmids [Clarke, L. & Carbon, J. (1976) Cell 9, 91-99] for those that correct the temperature sensitivity of a mutant in CDP-1,2-diacyl sn-glycerol:L-serine O-phosphatidyltransferase (EC 2.7.8.8, phosphatidylserine synthase). Two hybrid plasmids of this kind (pLC34-44 and pLC34-46) were identified and characterized. Strains carrying these plasmids overproduce the synthase by 6- to 15-fold, as demonstrated by assays of extracts and purification to homogeneity of the overproduced enzyme. The overproduced synthase, like the wild-type enzyme, is found associated predominately with the ribosomal fraction of crude cell extracts. Because the membrane phospholipid composition of these overproducers is not greatly altered, we suggest that the synthase is normally present in excess.", "contents": "Gene cloning for the isolation of enzymes of membrane lipid synthesis: phosphatidylserine synthase overproduction in Escherichia coli. We have screened a bank of 2000 E. coli strains carrying hybrid ColE1 plasmids [Clarke, L. & Carbon, J. (1976) Cell 9, 91-99] for those that correct the temperature sensitivity of a mutant in CDP-1,2-diacyl sn-glycerol:L-serine O-phosphatidyltransferase (EC 2.7.8.8, phosphatidylserine synthase). Two hybrid plasmids of this kind (pLC34-44 and pLC34-46) were identified and characterized. Strains carrying these plasmids overproduce the synthase by 6- to 15-fold, as demonstrated by assays of extracts and purification to homogeneity of the overproduced enzyme. The overproduced synthase, like the wild-type enzyme, is found associated predominately with the ribosomal fraction of crude cell extracts. Because the membrane phospholipid composition of these overproducers is not greatly altered, we suggest that the synthase is normally present in excess."}
{"id": "PMID:193100", "title": "Partial reaction of peptide initiation inhibited by phosphorylation of either initiation factor eIF-2 or 40S ribosomal proteins.", "content": "Preparations of the hemin-controlled repressor (HCR) from rabbit reticulocytes contain 3':5'-cyclic-AMP-independent protein kinase activity for the smallest subunit of the peptide initiation factor eIF-2 and for proteins of reticulocyte 40S ribosomal subunits. Binding of the ternary complex formed between Met-tRNAf, GTP, and eIF-2 to 40S ribosomal subunits is shown to be inhibited by phosphorylation of either the ribosomal subunits or eIF-2. The protein kinase activity responsible for phosphorylation of eIF-2 has been separated from the activity for phosphorylation of 40S ribosomal subunits and shown to independently block the same partial reaction of peptide initiation. It appears that different enzymes are involved, each capable of regulating peptide initiation at the same step but by a different mechanism.", "contents": "Partial reaction of peptide initiation inhibited by phosphorylation of either initiation factor eIF-2 or 40S ribosomal proteins. Preparations of the hemin-controlled repressor (HCR) from rabbit reticulocytes contain 3':5'-cyclic-AMP-independent protein kinase activity for the smallest subunit of the peptide initiation factor eIF-2 and for proteins of reticulocyte 40S ribosomal subunits. Binding of the ternary complex formed between Met-tRNAf, GTP, and eIF-2 to 40S ribosomal subunits is shown to be inhibited by phosphorylation of either the ribosomal subunits or eIF-2. The protein kinase activity responsible for phosphorylation of eIF-2 has been separated from the activity for phosphorylation of 40S ribosomal subunits and shown to independently block the same partial reaction of peptide initiation. It appears that different enzymes are involved, each capable of regulating peptide initiation at the same step but by a different mechanism."}
{"id": "PMID:193101", "title": "Role of 3':5'-cyclic-AMP-dependent protein kinase in regulation of protein synthesis in reticulocyte lysates.", "content": "The initiation inhibitor of reticulocyte lysates has been shown by others to be associated with a 3':5'-cyclic-AMP-independent protein kinase that catalyzes the phosphorylation of the small (38,000 daltons) subunit of the polypeptide chain initiation factor eIF-2. This factor forms a ternary complex with Met-tRNAi and GTP which, on interaction with a 40S ribosome, gives rise to a 40S complex. Ternary complex formation is inhibited by prior incubation of partially purified eIF-2 with reticulocyte inhibitor and ATP. The relation between phosphorylation and inactivation of eIF-2 is indicated by the lack of inhibition when ATP is omitted. Translation in hemin-containing reticulocyte lysates is also inhibited by cyclic-AMP-dependent protein kinases or their catalytic subunits. They act by converting proinhibitor (inactive eIF-2 kinase) present in lysates to inhibitor (active eIF-2 kinase). This reaction is analogous to the conversion of inactive phosphorylase kinase to active phosphorylase kinase.", "contents": "Role of 3':5'-cyclic-AMP-dependent protein kinase in regulation of protein synthesis in reticulocyte lysates. The initiation inhibitor of reticulocyte lysates has been shown by others to be associated with a 3':5'-cyclic-AMP-independent protein kinase that catalyzes the phosphorylation of the small (38,000 daltons) subunit of the polypeptide chain initiation factor eIF-2. This factor forms a ternary complex with Met-tRNAi and GTP which, on interaction with a 40S ribosome, gives rise to a 40S complex. Ternary complex formation is inhibited by prior incubation of partially purified eIF-2 with reticulocyte inhibitor and ATP. The relation between phosphorylation and inactivation of eIF-2 is indicated by the lack of inhibition when ATP is omitted. Translation in hemin-containing reticulocyte lysates is also inhibited by cyclic-AMP-dependent protein kinases or their catalytic subunits. They act by converting proinhibitor (inactive eIF-2 kinase) present in lysates to inhibitor (active eIF-2 kinase). This reaction is analogous to the conversion of inactive phosphorylase kinase to active phosphorylase kinase."}
{"id": "PMID:193102", "title": "Mechanism for acute control of fatty acid synthesis by glucagon and 3':5'-cyclic AMP in the liver cell.", "content": "Labeling experiments with chicken liver cell monolayers and suspensions show that glucagon and N6, O2-dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP) block fatty acid synthesis from acetate without appreciably affecting cholesterogenesis from acetate or acylglyceride synthesis from palmitate. Neither acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] activity assayed in the presence of citrate nor fatty acid synthetase activity is decreased in extracts of cells treated with glucagon. However, the cytoplasmic concentration of citrate, a required allosteric activator of acetyl-CoA carboxylase, is depressed more than 90% by glucagon or dibutyrl cyclic AMP. Pyruvate or lactate largely prevents the inhibitory action of these effectors on fatty acid synthesis by causing a large increase in cytoplasmic citrate level. Thus, it appears that glucagon, acting via cyclic AMP, inhibits fatty acid synthesis by blocking the formation of citrate, an essential activator of acetyl-CoA carboxylase.", "contents": "Mechanism for acute control of fatty acid synthesis by glucagon and 3':5'-cyclic AMP in the liver cell. Labeling experiments with chicken liver cell monolayers and suspensions show that glucagon and N6, O2-dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP) block fatty acid synthesis from acetate without appreciably affecting cholesterogenesis from acetate or acylglyceride synthesis from palmitate. Neither acetyl-CoA carboxylase [acetyl-CoA:carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] activity assayed in the presence of citrate nor fatty acid synthetase activity is decreased in extracts of cells treated with glucagon. However, the cytoplasmic concentration of citrate, a required allosteric activator of acetyl-CoA carboxylase, is depressed more than 90% by glucagon or dibutyrl cyclic AMP. Pyruvate or lactate largely prevents the inhibitory action of these effectors on fatty acid synthesis by causing a large increase in cytoplasmic citrate level. Thus, it appears that glucagon, acting via cyclic AMP, inhibits fatty acid synthesis by blocking the formation of citrate, an essential activator of acetyl-CoA carboxylase."}
{"id": "PMID:193103", "title": "Purified DNAs are transcribed after microinjection into Xenopus oocytes.", "content": "The possibility of using DNA-injected Xenopus laevis oocytes and eggs for studying the control of transcription in eukaryotes has been investigated. When purified DNA of simian virus 40 (SV40) is injected into Xenopus laevis oocytes, tritiated RNA precursors are incorporated into DNase-I-resistant, RNase-A- and alkali-sensitive material that hybridizes specifically to SV40 DNA. This viral transcription continues for at least 5 days and occurs only when the injected DNA is directed to the nucleus of the oocyte. The quantity of SV40-specific RNA produced is roughly proportional to the amount of DNA injected; above 1 ng per oocyte, most of the nonribosomal RNA made in successfully injected oocytes is virus-specific. Transcription also occurs, although at a lower efficiency, after injection of the DNA into unfertilized eggs. The DNAs of adenovirus 5, cloned Drosophila melanogaster histone genes, and even bacteriophage phiX174 replicative form, bacteriophage phi80plac, and the ColE1 plasmid are also transcribed after injection into oocytes or eggs.", "contents": "Purified DNAs are transcribed after microinjection into Xenopus oocytes. The possibility of using DNA-injected Xenopus laevis oocytes and eggs for studying the control of transcription in eukaryotes has been investigated. When purified DNA of simian virus 40 (SV40) is injected into Xenopus laevis oocytes, tritiated RNA precursors are incorporated into DNase-I-resistant, RNase-A- and alkali-sensitive material that hybridizes specifically to SV40 DNA. This viral transcription continues for at least 5 days and occurs only when the injected DNA is directed to the nucleus of the oocyte. The quantity of SV40-specific RNA produced is roughly proportional to the amount of DNA injected; above 1 ng per oocyte, most of the nonribosomal RNA made in successfully injected oocytes is virus-specific. Transcription also occurs, although at a lower efficiency, after injection of the DNA into unfertilized eggs. The DNAs of adenovirus 5, cloned Drosophila melanogaster histone genes, and even bacteriophage phiX174 replicative form, bacteriophage phi80plac, and the ColE1 plasmid are also transcribed after injection into oocytes or eggs."}
{"id": "PMID:193104", "title": "Synthesis and glycosylation in vitro of glycoprotein of vesicular stomatitis virus.", "content": "Coupling of ribonucleoprotein particles from L cells infected with vesicular stomatitis virus to a pre-incubated ribosomal system obtained from uninfected HeLa cells allowed synthesis of two proteins. G1 (molecular weight 63,000) and G2 (molecular weight 67,000), and all other proteins of vesicular stomatitis virus except the spike protein G (molecular weight 69,000). Analyses of the tryptic peptides showed that G1, G2, and G had identical peptide sequences. The synthesis of G2 required the presence of membranes; only G1 was synthesized in the absence of any membranes. G2 but not G1 was shown to be a glycoprotein by affinity chromatography on a concanavalin A-Sepharose column. Removal of sialic acid residues from G by neuraminidase resulted in a product having an identical mobility to G2. Digestion of G2 or G with a mixture of neuraminidase (EC 3.2.1.18), beta-galactosidase (EC 3.2.1.23), and beta-N-acetylglucosaminidase (EC 3.2.1.30), however, produced a protein of molecular weight 65,000. These data suggest that G2 is the desialated G and is formed by glycosylation of G1, which is the unglycosylated polypeptide backbone of G.", "contents": "Synthesis and glycosylation in vitro of glycoprotein of vesicular stomatitis virus. Coupling of ribonucleoprotein particles from L cells infected with vesicular stomatitis virus to a pre-incubated ribosomal system obtained from uninfected HeLa cells allowed synthesis of two proteins. G1 (molecular weight 63,000) and G2 (molecular weight 67,000), and all other proteins of vesicular stomatitis virus except the spike protein G (molecular weight 69,000). Analyses of the tryptic peptides showed that G1, G2, and G had identical peptide sequences. The synthesis of G2 required the presence of membranes; only G1 was synthesized in the absence of any membranes. G2 but not G1 was shown to be a glycoprotein by affinity chromatography on a concanavalin A-Sepharose column. Removal of sialic acid residues from G by neuraminidase resulted in a product having an identical mobility to G2. Digestion of G2 or G with a mixture of neuraminidase (EC 3.2.1.18), beta-galactosidase (EC 3.2.1.23), and beta-N-acetylglucosaminidase (EC 3.2.1.30), however, produced a protein of molecular weight 65,000. These data suggest that G2 is the desialated G and is formed by glycosylation of G1, which is the unglycosylated polypeptide backbone of G."}
{"id": "PMID:193105", "title": "Unified mechanism for relay and oscillation of cyclic AMP in Dictyostelium discoideum.", "content": "A modified version of an allosteric model for adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] previously analyzed for sustained oscillations of adenosine 3':5'-cyclic monophosphate (cAMP) in Dictyostelium discoideum [Goldbeter, A. (1975) Nature 253, 540-542] is examined to see whether it can account for the relay of cAMP pulses. Oscillations occur around a nonequilibrium, unstable stationary state when system parameters are in a certain domain. It is found that relay can occur outside this domain, in a restricted set of parameter values for which the solution ultimately tends to a stable steady state. A suprathreshold level of extracellular cAMP is needed to elicit relay which consists in a pulsatory synthesis of intracellular cAMP. Theoretical predictions are compared with the results of experiments on cAMP relay and oscillation in aggregation-competent cells of D. discoideum. The model suggests an explanation for the emergence of aggregation centers and for a sequence of developmental events observed in interphase amoebae.", "contents": "Unified mechanism for relay and oscillation of cyclic AMP in Dictyostelium discoideum. A modified version of an allosteric model for adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] previously analyzed for sustained oscillations of adenosine 3':5'-cyclic monophosphate (cAMP) in Dictyostelium discoideum [Goldbeter, A. (1975) Nature 253, 540-542] is examined to see whether it can account for the relay of cAMP pulses. Oscillations occur around a nonequilibrium, unstable stationary state when system parameters are in a certain domain. It is found that relay can occur outside this domain, in a restricted set of parameter values for which the solution ultimately tends to a stable steady state. A suprathreshold level of extracellular cAMP is needed to elicit relay which consists in a pulsatory synthesis of intracellular cAMP. Theoretical predictions are compared with the results of experiments on cAMP relay and oscillation in aggregation-competent cells of D. discoideum. The model suggests an explanation for the emergence of aggregation centers and for a sequence of developmental events observed in interphase amoebae."}
{"id": "PMID:193106", "title": "Electron spin resonance absorption of tissue constituents.", "content": "The electron spin resonance spectra at g = 2 of the structural and soluble proteins of mouse liver have been investigated separately. The structural materials have signals an order of magnitude stronger. Radicals with important similarities to those occurring in natural tissue can be induced by treating casein with methylglyoxal or crotonaldehyde. The structural proteins of cancer give little or no signal. The color of the proteins and their electron spin resonance signal seem closely related.", "contents": "Electron spin resonance absorption of tissue constituents. The electron spin resonance spectra at g = 2 of the structural and soluble proteins of mouse liver have been investigated separately. The structural materials have signals an order of magnitude stronger. Radicals with important similarities to those occurring in natural tissue can be induced by treating casein with methylglyoxal or crotonaldehyde. The structural proteins of cancer give little or no signal. The color of the proteins and their electron spin resonance signal seem closely related."}
{"id": "PMID:193107", "title": "Generation of macrophage migration inhibitory activity by plasminogen activators.", "content": "Medium from cultures of simian virus 40-transformed mouse 3T3 cells (SV3T3) inhibits the migration in vitro of peritoneal exudate cells (macrophages) from guinea pigs while medium from untransformed 3T3 cultures does not [Hammond, M. E., Robbin, R. D., Dvorak, A. M., Selvaggio, S. S., Black, P. H. & Dvorak, H. F. (1974) Science 185, 955-957]. The present paper describes the generation of migration inhibitory factor (MIF)-like activity for peritoneal exudate cells from guinea pigs after incubation of a serum-free harvest fluid from SV3T3 cells with guinea pig serum. Inhibited macrophages lose a densely staining material from the cell surface coat compared with uninhibited guinea pig peritoneal exudate cells. The factor in SV3T3 harvest fluids which generates the migration inhibitory activity appears to be plasminogen activator, i.e., a serine protease, because (i) plasminogen activator activity and the factor which generates MIF-like activity copurify, and co-chromatograph on Sephadex G-200 columns, and (ii) plasminogen activator activity and capacity to generate MIF-like activity are simultaneously lost upon treatment with [3H]diisopropylfluorophosphate. In addition, a purified preparation of a known plasminogen activator, human urokinase, can also generate MIF-like activity upon reaction with guinea pig serum. Because transformation of 3T3 cells by SV40 increases their plasminogen activator secretion, enhanced secretion of plasminogen activator by SV3T3 cells may explain why formation of MIF-like activity is observed in SV3T3 but not 3T3 cultures. These results reveal a biochemical pathway whereby a product secreted by virus-transformed cells affects one function of a cell central to the host's immunological defense system.", "contents": "Generation of macrophage migration inhibitory activity by plasminogen activators. Medium from cultures of simian virus 40-transformed mouse 3T3 cells (SV3T3) inhibits the migration in vitro of peritoneal exudate cells (macrophages) from guinea pigs while medium from untransformed 3T3 cultures does not [Hammond, M. E., Robbin, R. D., Dvorak, A. M., Selvaggio, S. S., Black, P. H. & Dvorak, H. F. (1974) Science 185, 955-957]. The present paper describes the generation of migration inhibitory factor (MIF)-like activity for peritoneal exudate cells from guinea pigs after incubation of a serum-free harvest fluid from SV3T3 cells with guinea pig serum. Inhibited macrophages lose a densely staining material from the cell surface coat compared with uninhibited guinea pig peritoneal exudate cells. The factor in SV3T3 harvest fluids which generates the migration inhibitory activity appears to be plasminogen activator, i.e., a serine protease, because (i) plasminogen activator activity and the factor which generates MIF-like activity copurify, and co-chromatograph on Sephadex G-200 columns, and (ii) plasminogen activator activity and capacity to generate MIF-like activity are simultaneously lost upon treatment with [3H]diisopropylfluorophosphate. In addition, a purified preparation of a known plasminogen activator, human urokinase, can also generate MIF-like activity upon reaction with guinea pig serum. Because transformation of 3T3 cells by SV40 increases their plasminogen activator secretion, enhanced secretion of plasminogen activator by SV3T3 cells may explain why formation of MIF-like activity is observed in SV3T3 but not 3T3 cultures. These results reveal a biochemical pathway whereby a product secreted by virus-transformed cells affects one function of a cell central to the host's immunological defense system."}
{"id": "PMID:193108", "title": "Transfer of the gene for thymidine kinase to thymidine kinase-deficient human cells by purified herpes simplex viral DNA.", "content": "Transformation of human cells from a thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75)-negative to a thymidine kinase-positive phenotype has been achieved by using purified DNA from herpes simplex virus type 2. The specific activity of the DNA was in the range 0.5 to 2.0 transformants per microng and the efficiency of gene transfer was up to 1 transformant per 10(5) recipient cells. Several transformed lines able to grow continuously in medium selective for thymidine kinase-positive cells have been established. All of these lines express a thymidine kinase activity of viral origin but they differ from each other in the stability of enzyme expression. Subclones derived from a given transformed line inherited the degree of stability of the parental line.", "contents": "Transfer of the gene for thymidine kinase to thymidine kinase-deficient human cells by purified herpes simplex viral DNA. Transformation of human cells from a thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75)-negative to a thymidine kinase-positive phenotype has been achieved by using purified DNA from herpes simplex virus type 2. The specific activity of the DNA was in the range 0.5 to 2.0 transformants per microng and the efficiency of gene transfer was up to 1 transformant per 10(5) recipient cells. Several transformed lines able to grow continuously in medium selective for thymidine kinase-positive cells have been established. All of these lines express a thymidine kinase activity of viral origin but they differ from each other in the stability of enzyme expression. Subclones derived from a given transformed line inherited the degree of stability of the parental line."}
{"id": "PMID:193109", "title": "Microinjection analysis of envelope-glycoprotein messenger activities of avian leukosis viral RNAs.", "content": "Virion RNA from the avian leukosis virus Rous-associated virus 2 (RAV-2) and poly(A)-containing RNAs from RAV-2-infected chick embryo fibroblasts were microinjected into fibroblasts transformed by the Bryan high-titer strain of Rous sarcoma virus (RSV), which is deficient in viral envelope glycoprotein. Production of infectious RSV following these injections depended upon the viral envelope-messenger activity of the injected RNA. This system constituted a sensitive and rigorous assay system for viral envelope-messenger RNA. It was found that 21S mRNA from RAV-2-infected cells expressed the highest activity, while 35S mRNA expressed comparatively little. In addition, RAV-2-virion RNA expressed little messenger activity. The rate of formation of infectious RSV following 21S mRNA injections reached a peak near 9 hr, which was followed by a rapid decline. Evidence has been obtained that a small fraction of both 35S virion RNA and 35S mRNA from virus-infected cells was encapsulated into virus particles following their injection into virus-producing cells.", "contents": "Microinjection analysis of envelope-glycoprotein messenger activities of avian leukosis viral RNAs. Virion RNA from the avian leukosis virus Rous-associated virus 2 (RAV-2) and poly(A)-containing RNAs from RAV-2-infected chick embryo fibroblasts were microinjected into fibroblasts transformed by the Bryan high-titer strain of Rous sarcoma virus (RSV), which is deficient in viral envelope glycoprotein. Production of infectious RSV following these injections depended upon the viral envelope-messenger activity of the injected RNA. This system constituted a sensitive and rigorous assay system for viral envelope-messenger RNA. It was found that 21S mRNA from RAV-2-infected cells expressed the highest activity, while 35S mRNA expressed comparatively little. In addition, RAV-2-virion RNA expressed little messenger activity. The rate of formation of infectious RSV following 21S mRNA injections reached a peak near 9 hr, which was followed by a rapid decline. Evidence has been obtained that a small fraction of both 35S virion RNA and 35S mRNA from virus-infected cells was encapsulated into virus particles following their injection into virus-producing cells."}
{"id": "PMID:193110", "title": "Quantitative determination of transformed cells in a mixed population by stimultaneous fluorescence analysis of cell surface and DNA an individual cells.", "content": "Cell-surface labeling with fluorescamine indicates that the fluorescence of Balb 3T3 A31 cells in considerably decreased after both viral and chemical transformation. This phenomenon, coupled with the technique of flow microfluorometry, enabled nontransformed and transformed cells to be distinguished. A second fluroescent probe, propidium iodide, which intercalates into DNA, was used in combination with fluorescamine in order to obtain a ratio of cell-surface labeling to DNA content. This manipulation allowed enhanced resolution of two populations and the detection of small numbers of transformants in a predominantly normal population.", "contents": "Quantitative determination of transformed cells in a mixed population by stimultaneous fluorescence analysis of cell surface and DNA an individual cells. Cell-surface labeling with fluorescamine indicates that the fluorescence of Balb 3T3 A31 cells in considerably decreased after both viral and chemical transformation. This phenomenon, coupled with the technique of flow microfluorometry, enabled nontransformed and transformed cells to be distinguished. A second fluroescent probe, propidium iodide, which intercalates into DNA, was used in combination with fluorescamine in order to obtain a ratio of cell-surface labeling to DNA content. This manipulation allowed enhanced resolution of two populations and the detection of small numbers of transformants in a predominantly normal population."}
{"id": "PMID:193111", "title": "Mapping of inverted repeated DNA sequences within the genome of simian virus 40.", "content": "Single-stranded, linear DNA of simian virus 40 (SV40) created by denaturing the endonuclease EcoRI- or Hpa II-generated, linear, double-stranded products from form I DNA of SV40 was analyzed for regions of inverted repeated sequences by visualization with the electron microscope. Six hairpin loops were found at positions 0.11-0.30 (two loops forming a \"rabbit ears\" structure), 0.47-0.52, 0.63-0.68, 0.70-0.76, and 0.90-0.96. The nucleotide sequences within all of these inverted repeats may be related since the looped regions can crosshybridize with one another and, thus, the SV40 genome may contain regions of interspersed repeated and unique sequences. The map positions of the 3' and 5' ends of the early and late messenger RNAs, as determined by others, lie within regions of inverted repeated sequences. Previously recorded recombination events that occurred either within the SV40 genome or between SV40 DNA and other genomes have apparently occurred frequently at positions of inverted repeated sequences within the SV40 DNA.", "contents": "Mapping of inverted repeated DNA sequences within the genome of simian virus 40. Single-stranded, linear DNA of simian virus 40 (SV40) created by denaturing the endonuclease EcoRI- or Hpa II-generated, linear, double-stranded products from form I DNA of SV40 was analyzed for regions of inverted repeated sequences by visualization with the electron microscope. Six hairpin loops were found at positions 0.11-0.30 (two loops forming a \"rabbit ears\" structure), 0.47-0.52, 0.63-0.68, 0.70-0.76, and 0.90-0.96. The nucleotide sequences within all of these inverted repeats may be related since the looped regions can crosshybridize with one another and, thus, the SV40 genome may contain regions of interspersed repeated and unique sequences. The map positions of the 3' and 5' ends of the early and late messenger RNAs, as determined by others, lie within regions of inverted repeated sequences. Previously recorded recombination events that occurred either within the SV40 genome or between SV40 DNA and other genomes have apparently occurred frequently at positions of inverted repeated sequences within the SV40 DNA."}
{"id": "PMID:193112", "title": "Immunoprevention of x-ray-induced leukemias in the C57BL mouse.", "content": "An attempt to prevent irradiation-induced thymic lymphomas in C57BL mice was made by inducing active immunity to endogenous type-C virus with inactivated Rauscher murine leukemia virus (MuLV) or inactivated Gross MuLV or by transferring passive immunity to endogenous type-C virus with goat anti-Gross MuLV IgG. Control groups received the following immunogen or treatment: inactivated simian sarcoma virus, complete Freund's adjuvant, normal goat IgG, and diluent, in both irradiated and nonirradiated C57BL mice Active immunity to the 70,000 molecular weight glycoprotein AKR-gp70 by immunization with Rauscher MuLV and passive immunity to AKR-gp70 by passive transfer of goat anti-Gross-MuLV IgG was measurable throughout some of the latent period of tumor development; in these two groups a significant reduction in tumor incidence was observed, as compared to the other experimental and control groups. Thus, the present findings support the concept of a type-C virus etiology of irradiation-induced leukemias and demonstrate the applicability of immunologic techniques directed against the endogenous type-C virus in the prevention of this disease.", "contents": "Immunoprevention of x-ray-induced leukemias in the C57BL mouse. An attempt to prevent irradiation-induced thymic lymphomas in C57BL mice was made by inducing active immunity to endogenous type-C virus with inactivated Rauscher murine leukemia virus (MuLV) or inactivated Gross MuLV or by transferring passive immunity to endogenous type-C virus with goat anti-Gross MuLV IgG. Control groups received the following immunogen or treatment: inactivated simian sarcoma virus, complete Freund's adjuvant, normal goat IgG, and diluent, in both irradiated and nonirradiated C57BL mice Active immunity to the 70,000 molecular weight glycoprotein AKR-gp70 by immunization with Rauscher MuLV and passive immunity to AKR-gp70 by passive transfer of goat anti-Gross-MuLV IgG was measurable throughout some of the latent period of tumor development; in these two groups a significant reduction in tumor incidence was observed, as compared to the other experimental and control groups. Thus, the present findings support the concept of a type-C virus etiology of irradiation-induced leukemias and demonstrate the applicability of immunologic techniques directed against the endogenous type-C virus in the prevention of this disease."}
{"id": "PMID:193113", "title": "Application of imidazole as a selective inhibitor thromboxane synthetase in human platelets.", "content": "Human platelet suspensions release a rabbit-aorta-contracting substance (previously identified as thromboxane A2) during aggregation produced by arachidonic acid, prostaglandin endoperoxide, thrombin, and collagen. Incubation of platelets with imidazole did not interfere with the aggregation produced by these agonists but markedly reduced the generation of the rabbit-aorta-contracting substance. We find that imidazole inhibited the conversion of exogenous or endogenous prostaglandin endoperoxide into thromboxane A2-Imidazole selectively inhibits thromboxane synthetase in intact human platelets, because this agent blocks the conversion of [14C]arachidonate into [14C]thromboxane B2 but does not inhibit the conversion of [14C]arachidonate into [14C]prostaglandin E2. The inhibition of thromboxane synthetase by imidazole is not the result of an alteration in platelet 3':5'-cyclic AMP levels. These results illustrate the utility of imidazole as a pharmacological tool and demonstrate the two unique and dissociable properties of the endoperoxides themselves--their ability to aggregate platelets and their enzymatic conversion to the potent vasoconstrictor thromboxane.", "contents": "Application of imidazole as a selective inhibitor thromboxane synthetase in human platelets. Human platelet suspensions release a rabbit-aorta-contracting substance (previously identified as thromboxane A2) during aggregation produced by arachidonic acid, prostaglandin endoperoxide, thrombin, and collagen. Incubation of platelets with imidazole did not interfere with the aggregation produced by these agonists but markedly reduced the generation of the rabbit-aorta-contracting substance. We find that imidazole inhibited the conversion of exogenous or endogenous prostaglandin endoperoxide into thromboxane A2-Imidazole selectively inhibits thromboxane synthetase in intact human platelets, because this agent blocks the conversion of [14C]arachidonate into [14C]thromboxane B2 but does not inhibit the conversion of [14C]arachidonate into [14C]prostaglandin E2. The inhibition of thromboxane synthetase by imidazole is not the result of an alteration in platelet 3':5'-cyclic AMP levels. These results illustrate the utility of imidazole as a pharmacological tool and demonstrate the two unique and dissociable properties of the endoperoxides themselves--their ability to aggregate platelets and their enzymatic conversion to the potent vasoconstrictor thromboxane."}
{"id": "PMID:193114", "title": "Relationship between serum sex hormones and glucose, insulin and lipid abnormalities in men with myocardial infarction.", "content": "Fifteen patients who had had a myocardial infarction before the age of 43 were compared with thirteen age-matched normal subjects. Twelve of the patients and three of the controls had a delayed glucose and insulin peak in the glucose and insulin areas than normal curves. When the measurements of the four patients with the largest areas under the glucose tolerance curve were separated, significant correlations were observed in the remaining patients and controls. The ratio in serum of the concentrations of estradiol-17beta to testosterone (E/T) correlated with serum glucose area (r equals + 0.69, P is less than 0.001), insulin area (r equals + 0.80, P is less than 0.001), and the ratio of insulin area to glucose area (I/G) (r equals + 0.64, P is less than 0.005) in the glucose tolerance test. Serum cholesterol concentration correlated with E/T, insulin area, and I/G, and serum triglyceride concentration correlated with glucose area, I/G, and serum cholesterol concentration. The hypothesis is presented (i) that in men who have had a myocardial infarction, an abnormality in glucose tolerance and insulin response and elevation in serum cholesterol and triglyceride concentrations are all part of the same defect (glucose-insulin-lipid defect), (ii) that this glucose-insulin-lipid defect when glucose intolerance is present is the \"mild diabetes\" commonly associated with myocardial infarction but is based on a mechanism different from that of classical diabetes, (iii) that this glucose-insulin-lipid defect is secondary to an elevation in E/T, and (iv) that an alteration in the sex hormone milieu is the major predisposing factor for myocardial infarction.", "contents": "Relationship between serum sex hormones and glucose, insulin and lipid abnormalities in men with myocardial infarction. Fifteen patients who had had a myocardial infarction before the age of 43 were compared with thirteen age-matched normal subjects. Twelve of the patients and three of the controls had a delayed glucose and insulin peak in the glucose and insulin areas than normal curves. When the measurements of the four patients with the largest areas under the glucose tolerance curve were separated, significant correlations were observed in the remaining patients and controls. The ratio in serum of the concentrations of estradiol-17beta to testosterone (E/T) correlated with serum glucose area (r equals + 0.69, P is less than 0.001), insulin area (r equals + 0.80, P is less than 0.001), and the ratio of insulin area to glucose area (I/G) (r equals + 0.64, P is less than 0.005) in the glucose tolerance test. Serum cholesterol concentration correlated with E/T, insulin area, and I/G, and serum triglyceride concentration correlated with glucose area, I/G, and serum cholesterol concentration. The hypothesis is presented (i) that in men who have had a myocardial infarction, an abnormality in glucose tolerance and insulin response and elevation in serum cholesterol and triglyceride concentrations are all part of the same defect (glucose-insulin-lipid defect), (ii) that this glucose-insulin-lipid defect when glucose intolerance is present is the \"mild diabetes\" commonly associated with myocardial infarction but is based on a mechanism different from that of classical diabetes, (iii) that this glucose-insulin-lipid defect is secondary to an elevation in E/T, and (iv) that an alteration in the sex hormone milieu is the major predisposing factor for myocardial infarction."}
{"id": "PMID:193115", "title": "Induction of deoxycytidine deaminase activity in mammalian cell lines by infection with herpes simplex virus type 1.", "content": "Herpes simplex virus type 1 induces deoxycytidine deaminase (cytidine/deoxycytidine aminohydrolase, EC 3.5.4.5) activity when it lytically infects a number of mammalian cell lines. The deaminase activity is induced in a mouse cell line that is deficient in this enzyme. The induction of the enzyme in this mutant cell line does not occur in the presence of actinomycin D and the induced enzyme is more thermolabile than the enzyme of the wild-type mouse cell line. Furthermore, a new deoxycytidine deaminase species with a characteristic electrophoretic mobility that is different from that of the host cell enzyme is found in cell extracts prepared from a human cell line infected with herpesvirus. These results strongly suggest that the virus-induced deoxycytidine deaminase is coded by the viral genome. Because a deficiency in this enzyme is conditionally lethal for cells growing in a medium containing 5-methyldeoxycytidine as the sole source of thymidylate, this enzyme can be utilized as a selective marker for selecting mutant cells that have regained deoxycytidine deaminase activity as the result of infection by ultraviolet-inactivated herpes simplex virus.", "contents": "Induction of deoxycytidine deaminase activity in mammalian cell lines by infection with herpes simplex virus type 1. Herpes simplex virus type 1 induces deoxycytidine deaminase (cytidine/deoxycytidine aminohydrolase, EC 3.5.4.5) activity when it lytically infects a number of mammalian cell lines. The deaminase activity is induced in a mouse cell line that is deficient in this enzyme. The induction of the enzyme in this mutant cell line does not occur in the presence of actinomycin D and the induced enzyme is more thermolabile than the enzyme of the wild-type mouse cell line. Furthermore, a new deoxycytidine deaminase species with a characteristic electrophoretic mobility that is different from that of the host cell enzyme is found in cell extracts prepared from a human cell line infected with herpesvirus. These results strongly suggest that the virus-induced deoxycytidine deaminase is coded by the viral genome. Because a deficiency in this enzyme is conditionally lethal for cells growing in a medium containing 5-methyldeoxycytidine as the sole source of thymidylate, this enzyme can be utilized as a selective marker for selecting mutant cells that have regained deoxycytidine deaminase activity as the result of infection by ultraviolet-inactivated herpes simplex virus."}
{"id": "PMID:193128", "title": "Insulin and fetal growth.", "content": "This review has examined the evidence from both clinical and experimental data that insulin has a key role in stimulating fetal growth. Human disorders where excessive insulin secretion and beta cell hyperplasia are present result in fetal overgrowth. Experimental models confirm an important anabolic effect of insulin in utero. Contrasted with this data is the evidence of intrauterine growth retardation occurring in association with insulinopenia or total absence of fetal insulin. Without the anabolic effect of insulin, no amount of substrate will induce optimal growth. It is evident from both the clinical and experimental data that sensitivity to insulin (probably individual receptor sites) develops in the latter stages of pregnancy. This point of sensitivity to the anabolic action of insulin has yet to be identified in a number of fetal tissues.", "contents": "Insulin and fetal growth. This review has examined the evidence from both clinical and experimental data that insulin has a key role in stimulating fetal growth. Human disorders where excessive insulin secretion and beta cell hyperplasia are present result in fetal overgrowth. Experimental models confirm an important anabolic effect of insulin in utero. Contrasted with this data is the evidence of intrauterine growth retardation occurring in association with insulinopenia or total absence of fetal insulin. Without the anabolic effect of insulin, no amount of substrate will induce optimal growth. It is evident from both the clinical and experimental data that sensitivity to insulin (probably individual receptor sites) develops in the latter stages of pregnancy. This point of sensitivity to the anabolic action of insulin has yet to be identified in a number of fetal tissues."}
{"id": "PMID:193132", "title": "Bactericidal mechanisms of the granulocyte.", "content": "Antimicrobial action of polymorphonuclear leukocytes depends on an array of substances carried in their cell membranes and cytoplasmic granules. These substances mediate killing in several systems. Some depend on molecular oxygen while others are independent of it. Some of the systems that depend on oxygen also require myeloperoxidase. The different systems seem able to act in primary or in reserve capacities backing each other up in times of stress or failure. Thus a deficiency in one system does not necessarily leave the polymorphs completely incapable of antimicrobial action although impairment may be severe as in chronic granulomatous disease. In general a poorly functioning polymorph is better than no polymorph at all.", "contents": "Bactericidal mechanisms of the granulocyte. Antimicrobial action of polymorphonuclear leukocytes depends on an array of substances carried in their cell membranes and cytoplasmic granules. These substances mediate killing in several systems. Some depend on molecular oxygen while others are independent of it. Some of the systems that depend on oxygen also require myeloperoxidase. The different systems seem able to act in primary or in reserve capacities backing each other up in times of stress or failure. Thus a deficiency in one system does not necessarily leave the polymorphs completely incapable of antimicrobial action although impairment may be severe as in chronic granulomatous disease. In general a poorly functioning polymorph is better than no polymorph at all."}
{"id": "PMID:193133", "title": "Extent of mitogen receptor occupancy and modulation of mitogen receptor exposure: possible mechanisms for the regulation of cell growth.", "content": "125I-Insulin was used as a model mitogen to examine the relationships of mitogen receptor occupancy and exposure in controlling cell replication. Labeled hormone was bound to substratum-attached, confluent fibroblasts with two affinities, K1 approximately equal to 2 X 108 M-1 and K2 approximately equal to 0.8 X 107 M-1. Approximately 9,000 receptors per cell were calculated from a scatchboard plot analysis with 80% of them of the affinity type. Treatment of confluent fibroblasts with 1.0 to 10 microng/ml of trypsin for 10 min increasd the number of exposed K2 sites by a factor of 2 to 3. Culturing the fibroblasts in the absence of serum for 12 to 24 hr also increased the quantity of exposed K2 sites to 60,000 per cell. The addition of unlabeled insulin to untreated, trypsin-treated, or serum-starved fibroblasts resulted in a stimulation of 2-deoxyglucose transport and thymidine incorporation activity that was proportional to the observed level of 125I-insulin binding. The quantity of exposed insulin receptors on uninfected fibroblasts decreases as the cell culture density increases. Hormone binding to B77 virus-transformed fibroblasts also decreases with culture density but plateaus at a density of 6 X 105 cells/plate. This resulted in a 2- to 3-fold difference in the level of exposed receptors between the uninfected and virus-transformed cells in confluent cultures, and proportionally higher rates of sugar transport and thymidine incorporation activity. Trypsin treatment and 12 hr of growth in the absence of serum did not result in an increase in the level of recepto exposure in the virus-transformed cells. The results of this study suggest that the pleotypic events associated with the stimulation of cell replication as represented by sugar transport and DNA synthesis are dependent upon and proportional to mitogen receptor occupancy. The control of cell replication, however, appears to be linked by a presently unknown mechanism with the degree of exposure of mitogen recipotrs. Receptor concentration is high and is similar in rapidly growing uninfected and virus-transformed cells, but the subsequent decrease observed with an increase in culture density reaches an early plateau for the transformed cells. This difference in exposed receptors could provide the growth advantage that is the hallmark of transformed cells.", "contents": "Extent of mitogen receptor occupancy and modulation of mitogen receptor exposure: possible mechanisms for the regulation of cell growth. 125I-Insulin was used as a model mitogen to examine the relationships of mitogen receptor occupancy and exposure in controlling cell replication. Labeled hormone was bound to substratum-attached, confluent fibroblasts with two affinities, K1 approximately equal to 2 X 108 M-1 and K2 approximately equal to 0.8 X 107 M-1. Approximately 9,000 receptors per cell were calculated from a scatchboard plot analysis with 80% of them of the affinity type. Treatment of confluent fibroblasts with 1.0 to 10 microng/ml of trypsin for 10 min increasd the number of exposed K2 sites by a factor of 2 to 3. Culturing the fibroblasts in the absence of serum for 12 to 24 hr also increased the quantity of exposed K2 sites to 60,000 per cell. The addition of unlabeled insulin to untreated, trypsin-treated, or serum-starved fibroblasts resulted in a stimulation of 2-deoxyglucose transport and thymidine incorporation activity that was proportional to the observed level of 125I-insulin binding. The quantity of exposed insulin receptors on uninfected fibroblasts decreases as the cell culture density increases. Hormone binding to B77 virus-transformed fibroblasts also decreases with culture density but plateaus at a density of 6 X 105 cells/plate. This resulted in a 2- to 3-fold difference in the level of exposed receptors between the uninfected and virus-transformed cells in confluent cultures, and proportionally higher rates of sugar transport and thymidine incorporation activity. Trypsin treatment and 12 hr of growth in the absence of serum did not result in an increase in the level of recepto exposure in the virus-transformed cells. The results of this study suggest that the pleotypic events associated with the stimulation of cell replication as represented by sugar transport and DNA synthesis are dependent upon and proportional to mitogen receptor occupancy. The control of cell replication, however, appears to be linked by a presently unknown mechanism with the degree of exposure of mitogen recipotrs. Receptor concentration is high and is similar in rapidly growing uninfected and virus-transformed cells, but the subsequent decrease observed with an increase in culture density reaches an early plateau for the transformed cells. This difference in exposed receptors could provide the growth advantage that is the hallmark of transformed cells."}
{"id": "PMID:193134", "title": "Further studies on the C5-derived chemotactic factor for tumor cells.", "content": "A factor has been studied that is chemotactic in vitro for Walker carcinosarcoma and Novikoff hepatoma cells of rats and for murine mastocytoma cells, but not for neutrophils. This chemotactic factor is generated by the incubation of normal serum with a crude extract from tumor cells. The generation of the tumor cell chemotactic factor is time and temperature dependent and results in greater than 30% reduction of serum complement activity. The tumor cell chemotatic factor appears to be a small cleavage product of the fifth complement component (C5) which binds to serum globulin. This has been shown by the use of agammaglobulinemic serum. By the use of isolated C5 fragments there is direct evidence that the tumor cell chemotactic factor is structurally derived from a larger C5 leukotactic fragment. The study of tumor cell chemotaxis, particularly the involvement of the complement system in this phenomenon, may suggest a novel approach to the investigation of the mechanism of metastasis in the malignant process.", "contents": "Further studies on the C5-derived chemotactic factor for tumor cells. A factor has been studied that is chemotactic in vitro for Walker carcinosarcoma and Novikoff hepatoma cells of rats and for murine mastocytoma cells, but not for neutrophils. This chemotactic factor is generated by the incubation of normal serum with a crude extract from tumor cells. The generation of the tumor cell chemotactic factor is time and temperature dependent and results in greater than 30% reduction of serum complement activity. The tumor cell chemotatic factor appears to be a small cleavage product of the fifth complement component (C5) which binds to serum globulin. This has been shown by the use of agammaglobulinemic serum. By the use of isolated C5 fragments there is direct evidence that the tumor cell chemotactic factor is structurally derived from a larger C5 leukotactic fragment. The study of tumor cell chemotaxis, particularly the involvement of the complement system in this phenomenon, may suggest a novel approach to the investigation of the mechanism of metastasis in the malignant process."}
{"id": "PMID:193138", "title": "Initial evaluation and management of patients with suspected pituitary tumors.", "content": "While pituitary tumors are not as rare as was once thought, it is difficult to assess how many are of clinical significance. Trans-sphenoidal pituitary exploration is a technique which can be performed with low operative morbidity and mortality, and when instituted early can prevent subsequent visual and endocrine impairment from an expanding lesion. Thus early recognition has increased importance.", "contents": "Initial evaluation and management of patients with suspected pituitary tumors. While pituitary tumors are not as rare as was once thought, it is difficult to assess how many are of clinical significance. Trans-sphenoidal pituitary exploration is a technique which can be performed with low operative morbidity and mortality, and when instituted early can prevent subsequent visual and endocrine impairment from an expanding lesion. Thus early recognition has increased importance."}
{"id": "PMID:193139", "title": "Adenosine 3'5' cyclic monophosphate metabolism in patients with severe depressive illness.", "content": "The daily excretion of adenosine 3'5' cyclic monophosphate (c-AMP) in a group of 19 patients with a severe depressive illness was found to be significantly decreased when compared with that from a group of euthymic patients being treated for other disorders in the same ward. The daily excretion of the depressed patients increased during the period of treatment and recovery from the illness. Treatment with a tricyclic antidepressant caused a greater increase than electroconvulsive treatment (ECT). There was no difference between the mean plasma c-AMP concentration of the depressed and euthymic groups. The mean CSF-c-AMP concentration was not different from the mean plasma c-AMP concentration in 12 patients with severe depression. There was no direct correlation between the CSF and plasma concentrations within patients. It was concluded that there may be a reversible disturbance in the renal metabolism of c-AMP in patients with severe depression.", "contents": "Adenosine 3'5' cyclic monophosphate metabolism in patients with severe depressive illness. The daily excretion of adenosine 3'5' cyclic monophosphate (c-AMP) in a group of 19 patients with a severe depressive illness was found to be significantly decreased when compared with that from a group of euthymic patients being treated for other disorders in the same ward. The daily excretion of the depressed patients increased during the period of treatment and recovery from the illness. Treatment with a tricyclic antidepressant caused a greater increase than electroconvulsive treatment (ECT). There was no difference between the mean plasma c-AMP concentration of the depressed and euthymic groups. The mean CSF-c-AMP concentration was not different from the mean plasma c-AMP concentration in 12 patients with severe depression. There was no direct correlation between the CSF and plasma concentrations within patients. It was concluded that there may be a reversible disturbance in the renal metabolism of c-AMP in patients with severe depression."}
{"id": "PMID:193141", "title": "[Statistical research on the lipides electrophoresis and on double pre-beta lipoprotein (author's transl)].", "content": "On 442 healthy subjects statistical research on cholesterol, triglycerides and lipoprotein electrophoresis on agarose was carried out. The results of statistical elaborations concerning average and standard deviation of the three lipoproteic bands (beta, pre-beta and alpha) are explained. 22 cases with double pre-beta lipoprotein (both normal and hyperlipoproteinaemic subjects) are described. The importance of this anomaly and its correlation with coronary atherosclerosis are pointed out.", "contents": "[Statistical research on the lipides electrophoresis and on double pre-beta lipoprotein (author's transl)]. On 442 healthy subjects statistical research on cholesterol, triglycerides and lipoprotein electrophoresis on agarose was carried out. The results of statistical elaborations concerning average and standard deviation of the three lipoproteic bands (beta, pre-beta and alpha) are explained. 22 cases with double pre-beta lipoprotein (both normal and hyperlipoproteinaemic subjects) are described. The importance of this anomaly and its correlation with coronary atherosclerosis are pointed out."}
{"id": "PMID:193136", "title": "Tissular cycli AMP levels after treatments with prostaglandins.", "content": "In this study both prostaglandin A1 (PGA1) and prostaglandin F2alpha (PGF2alpha) have been shown to be effective long-lasting stimulators of the cyclic AMP (cAMP) synthesis in the liver, intestinal mucosa and brain, whereas prostaglandin E1 (PGE1) was found to have a similar effect on the cerebral cAMP synthesis and a dissimilar effect (decrease) on the hepatic one. A lack of sensitivity of the intestinal mucosa cAMP to PGE1 was also observed.", "contents": "Tissular cycli AMP levels after treatments with prostaglandins. In this study both prostaglandin A1 (PGA1) and prostaglandin F2alpha (PGF2alpha) have been shown to be effective long-lasting stimulators of the cyclic AMP (cAMP) synthesis in the liver, intestinal mucosa and brain, whereas prostaglandin E1 (PGE1) was found to have a similar effect on the cerebral cAMP synthesis and a dissimilar effect (decrease) on the hepatic one. A lack of sensitivity of the intestinal mucosa cAMP to PGE1 was also observed."}
{"id": "PMID:193147", "title": "The postoperative myelogram. Radiographic evaluation of arachnoiditis and dural/arachnoidal tears.", "content": "Either arachnoriditis or dural/arachnoidal tears may cause symptoms in the postoperative spinal patient. Surgery and myelography as causes of arachnoiditis are discussed. Intradural arachnoid cyst formation and intramedullary cavitation may present as unusual sequelae of arachnoiditis. Extra-dural cysts and cerebrospinal fluid fistulas resulting from dural/arachnoidal tears are unusual postoperative complications presenting striking myelographic features. Their mechanisms of formation, clinical significance, and radiographic features are discussed.", "contents": "The postoperative myelogram. Radiographic evaluation of arachnoiditis and dural/arachnoidal tears. Either arachnoriditis or dural/arachnoidal tears may cause symptoms in the postoperative spinal patient. Surgery and myelography as causes of arachnoiditis are discussed. Intradural arachnoid cyst formation and intramedullary cavitation may present as unusual sequelae of arachnoiditis. Extra-dural cysts and cerebrospinal fluid fistulas resulting from dural/arachnoidal tears are unusual postoperative complications presenting striking myelographic features. Their mechanisms of formation, clinical significance, and radiographic features are discussed."}
{"id": "PMID:193152", "title": "The role of the blood in metabolism of prostaglandin E1 in the cat lung.", "content": "We found that when 15-keto-PGE1 was added to cat blood, it was converted to 13, 14-dihydro-15-keto-PGE1 (dihydro-keto-PGE1) by a NADH-dependent enzyme associated with some formed element(s) in the blood. When PGE1 was injected into the pulmonary artery of blood-perfused lungs, the only metabolite detectable in the pulmonary venous blood was the dihydro-keto-PGE1. However, when the lungs were perfused with an artificial perfusate containing no blood cells, a small amount of 15-keto-PGE1 was detected in the venous effluent. Therefore it would appear that a blood-borne delta13 reductase was partially responsible for the conversion of PGE1 to dihydro-keto-PGE1 on passage through blood-perfused cat lungs.", "contents": "The role of the blood in metabolism of prostaglandin E1 in the cat lung. We found that when 15-keto-PGE1 was added to cat blood, it was converted to 13, 14-dihydro-15-keto-PGE1 (dihydro-keto-PGE1) by a NADH-dependent enzyme associated with some formed element(s) in the blood. When PGE1 was injected into the pulmonary artery of blood-perfused lungs, the only metabolite detectable in the pulmonary venous blood was the dihydro-keto-PGE1. However, when the lungs were perfused with an artificial perfusate containing no blood cells, a small amount of 15-keto-PGE1 was detected in the venous effluent. Therefore it would appear that a blood-borne delta13 reductase was partially responsible for the conversion of PGE1 to dihydro-keto-PGE1 on passage through blood-perfused cat lungs."}
{"id": "PMID:193153", "title": "Inhibition of PGE1-stimulated cAMP accumulation in human platelets by thromboxane a2.", "content": "The prostaglandin endoperoxide PGH2, HHT, HETE, thromboxane A2, and thromboxane B2, which are all products of arachidonic acid metabolism of human platelets, were tested for their ability to modulate platelet cyclic nucleotide levels. None of the compounds tested altered the basal level of cAMP or cGMP, and only PGH2 and thromboxane A2 inhibited PGE1-stimulated cAMP accumulation. Thromboxane A2 was found to be a more potent inhibitor of PGE1-stimulated cAMP accumulation and inducer of platelet aggregation than PGH2.", "contents": "Inhibition of PGE1-stimulated cAMP accumulation in human platelets by thromboxane a2. The prostaglandin endoperoxide PGH2, HHT, HETE, thromboxane A2, and thromboxane B2, which are all products of arachidonic acid metabolism of human platelets, were tested for their ability to modulate platelet cyclic nucleotide levels. None of the compounds tested altered the basal level of cAMP or cGMP, and only PGH2 and thromboxane A2 inhibited PGE1-stimulated cAMP accumulation. Thromboxane A2 was found to be a more potent inhibitor of PGE1-stimulated cAMP accumulation and inducer of platelet aggregation than PGH2."}
{"id": "PMID:193154", "title": "Free and conjugated dihydroxyphenylacetic acid: effect of alterations in impulse flow in rat neostriatum and frontal cortex.", "content": "Stimulation of the nigro-neostriatal dopamine pathway results in an accumulation of both free and conjugated dihydroxy-phenylacetic acid (DOPAC) in the rat neostriatum. Drugs which have previously been shown to alter impulse flow in central dopaminergic neurons also produce predictable changes in the levels of both free and conjugated DOPAC in both the neostriatum and, in most cases, in the frontal cortex. Drugs such as the antipsychotics which increase impulse flow in the nigro-neostriatal dopamine neurons increase both free and conjugated DOPAC levels in both the neostriatum and frontal cortex. Drugs which reduce impulse flow, such as d-amphetamine and apomorphine, cause a reduction in free DOPAC in both the neostriatum and frontal cortex but reduce DOPAC conjugate only in the neostriatum. Pargyline, a monoamine oxidase inhibitor, causes an extensive depletion of free and conjugated DOPAC in both the striatum and frontal cortex, indicating that these metabolites are rapidly cleared from both of these brain areas.", "contents": "Free and conjugated dihydroxyphenylacetic acid: effect of alterations in impulse flow in rat neostriatum and frontal cortex. Stimulation of the nigro-neostriatal dopamine pathway results in an accumulation of both free and conjugated dihydroxy-phenylacetic acid (DOPAC) in the rat neostriatum. Drugs which have previously been shown to alter impulse flow in central dopaminergic neurons also produce predictable changes in the levels of both free and conjugated DOPAC in both the neostriatum and, in most cases, in the frontal cortex. Drugs such as the antipsychotics which increase impulse flow in the nigro-neostriatal dopamine neurons increase both free and conjugated DOPAC levels in both the neostriatum and frontal cortex. Drugs which reduce impulse flow, such as d-amphetamine and apomorphine, cause a reduction in free DOPAC in both the neostriatum and frontal cortex but reduce DOPAC conjugate only in the neostriatum. Pargyline, a monoamine oxidase inhibitor, causes an extensive depletion of free and conjugated DOPAC in both the striatum and frontal cortex, indicating that these metabolites are rapidly cleared from both of these brain areas."}
{"id": "PMID:193156", "title": "[Study of 67Ga distribution in neoplasms and in liver by a cell fractionation method].", "content": "Subcellular distribution of 67Ga was quantitatively determined to evaluate the role of lysosome in accumulation of 67Ga in malignant tumor tissue and liver. The following animals and transplanted tumors were used: rats implanted with Yoshida sarcoma and hepatoma AH109A; mice implanted with Ehrlich tumor. 67Ga-citrate were injected to the rats intravenously and to the mice intraperitoneally. Ten minutes to 48 hours after the administration of 67Ga-citrate, the animal were sacrificed, and the tumor tissues and liver were excised. Subcellular fractionation of tumor tissues and livers were carried out according to the method of Hogeboom and Schneider. Radioactivity of each fraction was counted by a well type scintillation counter, and protein of each fraction was measured according to Lowry's method. In Yoshida sarcoma and Ehrlich tumor, most of the radioactivity was localized in the supernatant fraction, and small amount of radioactivity was localized in the mitochodrial fraction (lysosome contains in this fraction). But in the liver, most of the radioactivity was concentrated in the mitochondrial fraction and the radioactivity of this fraction was increased with the passage of time after administration. Twenty-four hours later, about 50% of total radioactivity was accumulated in this fraction. In the case of hepatoma AH109A, radioactivity of mitochondrial fraction was increased with the passage of time after administration, and about 30% of total activity was concentrated in this fraction at 24 hours after administration. From these results it is concluded that lysosome doses not play an important role in the tumor concentration of 67Ga and lysosome plays an important role in the liver concentration of 67Ga. In the case of hepatoma AH109A it is presumed that lysosome plays considerably important role in the tumor concentration of 67Ga, hepatoma AH109A having some nature of liver.", "contents": "[Study of 67Ga distribution in neoplasms and in liver by a cell fractionation method]. Subcellular distribution of 67Ga was quantitatively determined to evaluate the role of lysosome in accumulation of 67Ga in malignant tumor tissue and liver. The following animals and transplanted tumors were used: rats implanted with Yoshida sarcoma and hepatoma AH109A; mice implanted with Ehrlich tumor. 67Ga-citrate were injected to the rats intravenously and to the mice intraperitoneally. Ten minutes to 48 hours after the administration of 67Ga-citrate, the animal were sacrificed, and the tumor tissues and liver were excised. Subcellular fractionation of tumor tissues and livers were carried out according to the method of Hogeboom and Schneider. Radioactivity of each fraction was counted by a well type scintillation counter, and protein of each fraction was measured according to Lowry's method. In Yoshida sarcoma and Ehrlich tumor, most of the radioactivity was localized in the supernatant fraction, and small amount of radioactivity was localized in the mitochodrial fraction (lysosome contains in this fraction). But in the liver, most of the radioactivity was concentrated in the mitochondrial fraction and the radioactivity of this fraction was increased with the passage of time after administration. Twenty-four hours later, about 50% of total radioactivity was accumulated in this fraction. In the case of hepatoma AH109A, radioactivity of mitochondrial fraction was increased with the passage of time after administration, and about 30% of total activity was concentrated in this fraction at 24 hours after administration. From these results it is concluded that lysosome doses not play an important role in the tumor concentration of 67Ga and lysosome plays an important role in the liver concentration of 67Ga. In the case of hepatoma AH109A it is presumed that lysosome plays considerably important role in the tumor concentration of 67Ga, hepatoma AH109A having some nature of liver."}
{"id": "PMID:193163", "title": "[Effect of the bilateral olfactory bulbs removal on the daily fluctuations on the plasmatic corticosterone levels (author's transl)].", "content": "The influence of the bilateral destruction of the olfactory bulbs on the circadian rhythm of plasmatic corticosterone in rat was investigated. Twentyfive days after bulbectomy, the values of corticosterone in the morning and in the evening were not significantly different. The possible involvement of the stria medularis, habenula, septum and preoptic area in the determination of this phenomenon is discussed.", "contents": "[Effect of the bilateral olfactory bulbs removal on the daily fluctuations on the plasmatic corticosterone levels (author's transl)]. The influence of the bilateral destruction of the olfactory bulbs on the circadian rhythm of plasmatic corticosterone in rat was investigated. Twentyfive days after bulbectomy, the values of corticosterone in the morning and in the evening were not significantly different. The possible involvement of the stria medularis, habenula, septum and preoptic area in the determination of this phenomenon is discussed."}
{"id": "PMID:193167", "title": "Autonomic and cardiovascular effects of chronic delta9-tetrahydrocannabinol administration in mongrel dogs.", "content": "Chronic administration of delta9-tetrahydrocannabinol (delta9-THC) 1mg/1kg, s.c., twice a day for 7 days failed to produce any major changes in the pulmonary or systemic hemodynamics and in the myocardial contractility of the mongrel dogs. Chronic delta9-THC treatment did not result in any significant alterations either in the transmission in the lumbar sympathetic chain or in the activity of autonomic receptors within the cardiovascular system. Further systemic pressor responses to bilateral carotid occlusion and reflexly mediated alterations in the perfused hindlimb vascular resistance were essentially identical in both the treated and placebo groups. Pressure-flow curves obtained from the perfused hindlimb preparations suggested that in contrast to the acute studies, neurogenic tone to the hindlimb vasculature was unaltered by chronic delta9-THC and intrinsic tone of the vascular smooth muscle was significantly depressed in the treated animals; in addition it appears that the tone due to circulating catecholamines was significantly enhanced in treated animals. The results of this investigation demonstrated that several acute cardiovascular and autonomic effects of delta9-THC may not be evident following chronic THC-treatment, however, prolonged use may demonstrate certain new pharmacological properties and/or mechanism of actions which cannot readily be seen in the acute studies.", "contents": "Autonomic and cardiovascular effects of chronic delta9-tetrahydrocannabinol administration in mongrel dogs. Chronic administration of delta9-tetrahydrocannabinol (delta9-THC) 1mg/1kg, s.c., twice a day for 7 days failed to produce any major changes in the pulmonary or systemic hemodynamics and in the myocardial contractility of the mongrel dogs. Chronic delta9-THC treatment did not result in any significant alterations either in the transmission in the lumbar sympathetic chain or in the activity of autonomic receptors within the cardiovascular system. Further systemic pressor responses to bilateral carotid occlusion and reflexly mediated alterations in the perfused hindlimb vascular resistance were essentially identical in both the treated and placebo groups. Pressure-flow curves obtained from the perfused hindlimb preparations suggested that in contrast to the acute studies, neurogenic tone to the hindlimb vasculature was unaltered by chronic delta9-THC and intrinsic tone of the vascular smooth muscle was significantly depressed in the treated animals; in addition it appears that the tone due to circulating catecholamines was significantly enhanced in treated animals. The results of this investigation demonstrated that several acute cardiovascular and autonomic effects of delta9-THC may not be evident following chronic THC-treatment, however, prolonged use may demonstrate certain new pharmacological properties and/or mechanism of actions which cannot readily be seen in the acute studies."}
{"id": "PMID:193168", "title": "Enhancement of the cardiac phosphorylase activating effect of dibutyryl cyclic AMP by thyroid hormone.", "content": "The injection of dibutyryl cyclic AMP into the perfused rat heart resulted in dose-dependent increases in contractile force and phosphorylase a activity. In hearts from hyperthyroid animals both responses were markedly enhanced. The data indicate that the hyperthyroid state may produce changes in the heart making it more responsive to cyclic AMP. Such a change could occur at the level of protein kinase. The data may also indicate that, in hyperthyroidism, the heart is more capable of taking up dibutyryl cyclic AMP or of converting it to an active product.", "contents": "Enhancement of the cardiac phosphorylase activating effect of dibutyryl cyclic AMP by thyroid hormone. The injection of dibutyryl cyclic AMP into the perfused rat heart resulted in dose-dependent increases in contractile force and phosphorylase a activity. In hearts from hyperthyroid animals both responses were markedly enhanced. The data indicate that the hyperthyroid state may produce changes in the heart making it more responsive to cyclic AMP. Such a change could occur at the level of protein kinase. The data may also indicate that, in hyperthyroidism, the heart is more capable of taking up dibutyryl cyclic AMP or of converting it to an active product."}
{"id": "PMID:193169", "title": "Affinities of opiate agonists and antagonists for the enkephalin receptors of rat brain.", "content": "The binding of 3H-enkephalin (methionine-enkephalin) to membranes of rat brain is inhibited by enkephalin and levorphanol with IC50 values of 5 and 1.6 nM, respectively. Dextrorphan, the optical isomer of levorphanol, is over 6,000 times less effective. Opiate agonists, morphine, dihydromorphine and l-methadone and opiate antagonists, naltrexone and naloxone are less effective inhibitors of 3H-enkephalin than in 3H-dihydromorphine and 3H-naloxone binding. However, opiates without the oxygen bridge as in the structure of morphine, such as levorphanol and the benzomorphans show affinities for the receptors of 3H-enkephalin equal or greater than their affinities for the receptors of 3H-opiates.", "contents": "Affinities of opiate agonists and antagonists for the enkephalin receptors of rat brain. The binding of 3H-enkephalin (methionine-enkephalin) to membranes of rat brain is inhibited by enkephalin and levorphanol with IC50 values of 5 and 1.6 nM, respectively. Dextrorphan, the optical isomer of levorphanol, is over 6,000 times less effective. Opiate agonists, morphine, dihydromorphine and l-methadone and opiate antagonists, naltrexone and naloxone are less effective inhibitors of 3H-enkephalin than in 3H-dihydromorphine and 3H-naloxone binding. However, opiates without the oxygen bridge as in the structure of morphine, such as levorphanol and the benzomorphans show affinities for the receptors of 3H-enkephalin equal or greater than their affinities for the receptors of 3H-opiates."}
{"id": "PMID:193170", "title": "Composition of some urinary calculi of ruminants in Western Australia.", "content": "Forty ruminant urinary calculi, selected as being essentially inorganic and mainly obtained from sheep grazing in the drier wheatbelt areas of Western Australia, were examined by optical and X-ray diffraction techniques. Four mineral types-silica (SiO2-nH2O), weddellite (CaC2O4-2H2O), calcite (CaCO3) and aragonite (CaCO3)--were found. These minerals were present respectively in 30, 17, 13 and 1 of the 40 calculi examined and were the sole component in 12, 0, 7, and 0 calculi. One calculus was found to be composed of organic material which was subsequently shown to consist mainly of 4'-O methyl equol (4'-methoxy-7-isoflavanol, C16H16O3) with a small amount of equol and a trace of formononetin. This is the first report of a calculus of this composition. Determinative data useful for identification of 4'o-methyl equol, equol and a related substance are presented in an appendix.", "contents": "Composition of some urinary calculi of ruminants in Western Australia. Forty ruminant urinary calculi, selected as being essentially inorganic and mainly obtained from sheep grazing in the drier wheatbelt areas of Western Australia, were examined by optical and X-ray diffraction techniques. Four mineral types-silica (SiO2-nH2O), weddellite (CaC2O4-2H2O), calcite (CaCO3) and aragonite (CaCO3)--were found. These minerals were present respectively in 30, 17, 13 and 1 of the 40 calculi examined and were the sole component in 12, 0, 7, and 0 calculi. One calculus was found to be composed of organic material which was subsequently shown to consist mainly of 4'-O methyl equol (4'-methoxy-7-isoflavanol, C16H16O3) with a small amount of equol and a trace of formononetin. This is the first report of a calculus of this composition. Determinative data useful for identification of 4'o-methyl equol, equol and a related substance are presented in an appendix."}
{"id": "PMID:193171", "title": "Immunoglobulins in the serum and nasal secretions of lambs following vaccination and aerosol challenge with parainfluenza 3 virus.", "content": "Serial changes in the concentrations of IgM, IgG and IgA were compared in specific pathogen free (SPF) lambs which had been vaccinated with live or inactivated parainfluenza 3 virus (PI 3) by either intramuscular (IM) or intranasal (IN) routes followed by aerosol challenge with PI 3. In the serum, an increase in IgM was associated with the primary antibody response to the aerosol challenge, whereas increased IgG was associated with the secondary antibody response. No changes in immunoglobulin concentrations were observed in the nasal secretions of lambs administered live or inactivated virus IM or IN without adjuvant. Marked increases in IgG were found in the serum and nasal secretions of lambs vaccinated IM with inactivated virus in Freund's complete adjuvant (FCA) and fractionation by gel filtration confirmed that the antibody was associated with IgG in both these fluids.", "contents": "Immunoglobulins in the serum and nasal secretions of lambs following vaccination and aerosol challenge with parainfluenza 3 virus. Serial changes in the concentrations of IgM, IgG and IgA were compared in specific pathogen free (SPF) lambs which had been vaccinated with live or inactivated parainfluenza 3 virus (PI 3) by either intramuscular (IM) or intranasal (IN) routes followed by aerosol challenge with PI 3. In the serum, an increase in IgM was associated with the primary antibody response to the aerosol challenge, whereas increased IgG was associated with the secondary antibody response. No changes in immunoglobulin concentrations were observed in the nasal secretions of lambs administered live or inactivated virus IM or IN without adjuvant. Marked increases in IgG were found in the serum and nasal secretions of lambs vaccinated IM with inactivated virus in Freund's complete adjuvant (FCA) and fractionation by gel filtration confirmed that the antibody was associated with IgG in both these fluids."}
{"id": "PMID:193172", "title": "The immunodepressive effect of infectious bursal agent on vaccination against Newcastle disease.", "content": "Immunodepression due to an infectious bursal agent (IBA) infection depends on the age of the birds, the time of Newcastle disease (ND) vaccination and the IBA strain used. The immunodepressive effect of IBA on ND vaccination can be avoided by vaccinating the chicks against ND at day old or by using attenuated strains of IBA in all commercial vaccines.", "contents": "The immunodepressive effect of infectious bursal agent on vaccination against Newcastle disease. Immunodepression due to an infectious bursal agent (IBA) infection depends on the age of the birds, the time of Newcastle disease (ND) vaccination and the IBA strain used. The immunodepressive effect of IBA on ND vaccination can be avoided by vaccinating the chicks against ND at day old or by using attenuated strains of IBA in all commercial vaccines."}
{"id": "PMID:193176", "title": "[Contribution of superselective arteriography and embolization in maxillofacial surgery. Apropos of 2 cases].", "content": "After describing the technique of embolisation and its therapeutic indications,the authors present two cases of different indications:--embolisation as the sole treatment,--pre-operative embolisation of a haemorrhagec tumour. These two cases illustrate two applications of the technique of embolisation:--Medical therapeutic value: making possible the reduction or stabilisation of the size of a vascular tumour difficult to excise surgically, in addition to eliminating the complications (haemorrhage, local trophic disturbance, pain);--Surgical interest: elective lesional embolisation such as is carried out at present greatly facilitates the surgical procedure in operations which may be associated with severe bleeding. Problems of healing are avoided. The procedure is carried out at the same time as selective arteriography. When in the hands of a skilled team, scarcely any risk is involved.", "contents": "[Contribution of superselective arteriography and embolization in maxillofacial surgery. Apropos of 2 cases]. After describing the technique of embolisation and its therapeutic indications,the authors present two cases of different indications:--embolisation as the sole treatment,--pre-operative embolisation of a haemorrhagec tumour. These two cases illustrate two applications of the technique of embolisation:--Medical therapeutic value: making possible the reduction or stabilisation of the size of a vascular tumour difficult to excise surgically, in addition to eliminating the complications (haemorrhage, local trophic disturbance, pain);--Surgical interest: elective lesional embolisation such as is carried out at present greatly facilitates the surgical procedure in operations which may be associated with severe bleeding. Problems of healing are avoided. The procedure is carried out at the same time as selective arteriography. When in the hands of a skilled team, scarcely any risk is involved."}
{"id": "PMID:193177", "title": "[Psychosomatic insomnia].", "content": "In presenting a case of extreme hyposomnia, psychosomatic insomnia is elaborated as a special type of primary insomnia. The case study of a 60 years old man is based on psychiatric examinations, an intersive one-week observation including polygraphic sleep recordings, and on reviewing medical data over a period of 35 years. In this case, the insomnia developed during a life situation with social stress and continued over 30 years with a gradual sleep reduction to 2-4 hours. Our sleep recordings confirmed a total sleep time of nearly 3 hours, a marked rhythmicity of sleep and day-time activities, fragmentation of sleep, and psychogenic extrasystoles, all symptoms having been reported by the subject previously. Autonomic functions indicated a good efficiency of NREM sleep, whereas a first night effect with subsequent adaptation revealed a good regulatory function of the sleep-waking-system. In addition to a detailed documentation of this extraordinary case, an interpretation is undertaken in order to explain, how the insomnia developed and continued. Psychodynamic aspects show a set of characteristics which are most typical for psychosomatic syndroms. The authors expect, that the knowledge about psychosomatic insomnia will be helpful in diagnosis and treatment of severe insomnias.", "contents": "[Psychosomatic insomnia]. In presenting a case of extreme hyposomnia, psychosomatic insomnia is elaborated as a special type of primary insomnia. The case study of a 60 years old man is based on psychiatric examinations, an intersive one-week observation including polygraphic sleep recordings, and on reviewing medical data over a period of 35 years. In this case, the insomnia developed during a life situation with social stress and continued over 30 years with a gradual sleep reduction to 2-4 hours. Our sleep recordings confirmed a total sleep time of nearly 3 hours, a marked rhythmicity of sleep and day-time activities, fragmentation of sleep, and psychogenic extrasystoles, all symptoms having been reported by the subject previously. Autonomic functions indicated a good efficiency of NREM sleep, whereas a first night effect with subsequent adaptation revealed a good regulatory function of the sleep-waking-system. In addition to a detailed documentation of this extraordinary case, an interpretation is undertaken in order to explain, how the insomnia developed and continued. Psychodynamic aspects show a set of characteristics which are most typical for psychosomatic syndroms. The authors expect, that the knowledge about psychosomatic insomnia will be helpful in diagnosis and treatment of severe insomnias."}
{"id": "PMID:193173", "title": "[Uremic neuropathy. Study of the motor conduction rate in patients treated with maintenance hemodialysis and peritoneal dialysis].", "content": "Forty-four patients, treated with different systems of dialysis (peritoneal dialysis, two-weekly and three-weekly hemodialysis) have been controlled by electroneurographic, electromyographic and ematochimical examinations during a six months to five years period. The results can be summarized as follow: a) motor nerve conduction velocity of the peroneal nerve is reduced proportionally to the clinical status in all patients. Motor nerve conduction velocity of the ulnar nerve is reduced only in the most severe cases; b) there are no significant correlations between the examined ematochimical data and the maximal motor nerve conduction velocity; c) there is a slight improvement of the maximal motor nerve conduction velocity of the peroneal nerve when passing from a twelve hours two weekly dialytic treatment to a five hours three weekly hemodialytic treatment. Motor nerve conduction velocity is therefore a reliable index of insufficient or adequate dialysis. Moreover it is confirmed the efficacy of a treatment with short and frequent dialytic sessions.", "contents": "[Uremic neuropathy. Study of the motor conduction rate in patients treated with maintenance hemodialysis and peritoneal dialysis]. Forty-four patients, treated with different systems of dialysis (peritoneal dialysis, two-weekly and three-weekly hemodialysis) have been controlled by electroneurographic, electromyographic and ematochimical examinations during a six months to five years period. The results can be summarized as follow: a) motor nerve conduction velocity of the peroneal nerve is reduced proportionally to the clinical status in all patients. Motor nerve conduction velocity of the ulnar nerve is reduced only in the most severe cases; b) there are no significant correlations between the examined ematochimical data and the maximal motor nerve conduction velocity; c) there is a slight improvement of the maximal motor nerve conduction velocity of the peroneal nerve when passing from a twelve hours two weekly dialytic treatment to a five hours three weekly hemodialytic treatment. Motor nerve conduction velocity is therefore a reliable index of insufficient or adequate dialysis. Moreover it is confirmed the efficacy of a treatment with short and frequent dialytic sessions."}
{"id": "PMID:193178", "title": "[Early mobilization in the acute stage of myocardial infarction long term results].", "content": "A report is presented on the continuation of a controlled study on early mobilization after acute myocardial infarction performed at the Cantonal Hospital of Geneva. Detailed follow-up studies were made in the patients from the original study 4 years on average after the myocardial infarction. It is well known that early mobilization offers many advantages over prolonged bed rest. The present study demonstrates that early mobilization after acute myocardial infarction involves no longterm risks.", "contents": "[Early mobilization in the acute stage of myocardial infarction long term results]. A report is presented on the continuation of a controlled study on early mobilization after acute myocardial infarction performed at the Cantonal Hospital of Geneva. Detailed follow-up studies were made in the patients from the original study 4 years on average after the myocardial infarction. It is well known that early mobilization offers many advantages over prolonged bed rest. The present study demonstrates that early mobilization after acute myocardial infarction involves no longterm risks."}
{"id": "PMID:193180", "title": "Problems in the diagnosis of Cushing's syndrome.", "content": "The diagnosis of florid Cushing's syndrome is usually made without difficulty but diagnostic problems may arise. Five such cases are described. Difficulties may occur when the features of the syndrome are incomplete. Three such cases were encountered. In each only one clinical feature was present; these respectively were hypertension, osteoporosis and obesity. The diagnosis was confirmed, however, biochemically and eventually histologically and there was a good response to surgery in each case. Another diagnostic problem, both clinically and biochemically is the obese, hirsute, hypertensive female. Two such cases are described, in whom Cushing's syndrome was diagnosed clinically and biochemically but in whom there was no response to adrenalectomy. Retrospectively the validity of the original diagnosis is questioned. It is concluded that Cushing's syndrome may present in a very incomplete form and should be considered in the differential diagnosis, even if only one feature is present. It is stressed that obesity, hirsutism, hypertension and depression are commonly found in association with normal adrenal function. Urinary free cortisol and cortisol response to insulin induced hypoglycaemia may be of value in distinguishing these cases from those with endocrine disease.", "contents": "Problems in the diagnosis of Cushing's syndrome. The diagnosis of florid Cushing's syndrome is usually made without difficulty but diagnostic problems may arise. Five such cases are described. Difficulties may occur when the features of the syndrome are incomplete. Three such cases were encountered. In each only one clinical feature was present; these respectively were hypertension, osteoporosis and obesity. The diagnosis was confirmed, however, biochemically and eventually histologically and there was a good response to surgery in each case. Another diagnostic problem, both clinically and biochemically is the obese, hirsute, hypertensive female. Two such cases are described, in whom Cushing's syndrome was diagnosed clinically and biochemically but in whom there was no response to adrenalectomy. Retrospectively the validity of the original diagnosis is questioned. It is concluded that Cushing's syndrome may present in a very incomplete form and should be considered in the differential diagnosis, even if only one feature is present. It is stressed that obesity, hirsutism, hypertension and depression are commonly found in association with normal adrenal function. Urinary free cortisol and cortisol response to insulin induced hypoglycaemia may be of value in distinguishing these cases from those with endocrine disease."}
{"id": "PMID:193181", "title": "Tumor cell collagenase and its inhibition by a cartilage-derived protease inhibitor.", "content": "Human osteosarcoma and mammary carcinoma cells were cultured separately in a medium supplemented with fetal calf serum, until they were confluent. The medium was then replaced by serum-free medium supplemented with heparin. Both cell cultures secreted collagenase, and this activity was inhibited by a cartilage-derived protein of low molecular weight. Since cartilage is rarely invaded by neoplasms, the presence of this inhibitor may play an important role in the regulation of tumor invasion.", "contents": "Tumor cell collagenase and its inhibition by a cartilage-derived protease inhibitor. Human osteosarcoma and mammary carcinoma cells were cultured separately in a medium supplemented with fetal calf serum, until they were confluent. The medium was then replaced by serum-free medium supplemented with heparin. Both cell cultures secreted collagenase, and this activity was inhibited by a cartilage-derived protein of low molecular weight. Since cartilage is rarely invaded by neoplasms, the presence of this inhibitor may play an important role in the regulation of tumor invasion."}
{"id": "PMID:193179", "title": "Studies on the mechanisms of abortion induction by Trichosanthin.", "content": "Radix trichosanthis, an abortifacient drug of mid-gestation, is extracted from the root tuber of Trichosanthes kirilowii Maxim, Cucurbitaceae. Its purified effective principle is a basic protein of molecular weight of approximately 18,000 and is named trichosanthin. By authorization it has been proved to be very effective in abortion induction of mid-gestation, particularly effective in curing ectopic pregnancy, hydatidiform mole, and invasive mole, and it has also some therapeutic action on choriocarcinoma. From the analysis of the experimental results on its initial site of action, the morphological and functional injury of trophoblast cells of placenta and of cultures in vitro and the effect on prostaglandin synthesis, the following conclusions are drawn concerning the mechanisms of abortion induction by trichosanthin: (1) Trichosanthin exerts its action directly on the placental trophoblasts and possesses a certain degree of specificity; (2) It selectively causes the necrotic denaturation of the syncytiotrophoblasts of placental villi, which makes fragments of the disintegrated cells clumped in the blood sinus, hence the coagulation of blood and the circulation hindrance, and tissue necrosis over large areas follows. The necrosis of placental villi is the primary response, and circulation hindrance secondary; (3) Structural injuries have been reflected on the impairment of functional activities; the concentrations of HCG and steroid hormones fall rapidly below the threshold values of threatened abortion. Serious structural and functional injuries bring about destructive disturbances on the normal endocrine relationship between the mother and the fetus and on metabolic exchanges. It is further postulated that through certain unknown mechanism the synthesis of prostaglandins increases, uterine contraction is initiated and abortion ensues. In summary, trichosanthin, a plant protein discovered from Chinese medicinal herbs, is a drug effective in abortion induction and against trophoblastic neoplasms. Preliminary elucidation of the mechanisms of abortion induction by trichosanthin has afforded a basis for the clinical application with better efficacy and its possible abortifacient use in early pregnancy and for the discovery of newer cancer chemotherapeutic agents.", "contents": "Studies on the mechanisms of abortion induction by Trichosanthin. Radix trichosanthis, an abortifacient drug of mid-gestation, is extracted from the root tuber of Trichosanthes kirilowii Maxim, Cucurbitaceae. Its purified effective principle is a basic protein of molecular weight of approximately 18,000 and is named trichosanthin. By authorization it has been proved to be very effective in abortion induction of mid-gestation, particularly effective in curing ectopic pregnancy, hydatidiform mole, and invasive mole, and it has also some therapeutic action on choriocarcinoma. From the analysis of the experimental results on its initial site of action, the morphological and functional injury of trophoblast cells of placenta and of cultures in vitro and the effect on prostaglandin synthesis, the following conclusions are drawn concerning the mechanisms of abortion induction by trichosanthin: (1) Trichosanthin exerts its action directly on the placental trophoblasts and possesses a certain degree of specificity; (2) It selectively causes the necrotic denaturation of the syncytiotrophoblasts of placental villi, which makes fragments of the disintegrated cells clumped in the blood sinus, hence the coagulation of blood and the circulation hindrance, and tissue necrosis over large areas follows. The necrosis of placental villi is the primary response, and circulation hindrance secondary; (3) Structural injuries have been reflected on the impairment of functional activities; the concentrations of HCG and steroid hormones fall rapidly below the threshold values of threatened abortion. Serious structural and functional injuries bring about destructive disturbances on the normal endocrine relationship between the mother and the fetus and on metabolic exchanges. It is further postulated that through certain unknown mechanism the synthesis of prostaglandins increases, uterine contraction is initiated and abortion ensues. In summary, trichosanthin, a plant protein discovered from Chinese medicinal herbs, is a drug effective in abortion induction and against trophoblastic neoplasms. Preliminary elucidation of the mechanisms of abortion induction by trichosanthin has afforded a basis for the clinical application with better efficacy and its possible abortifacient use in early pregnancy and for the discovery of newer cancer chemotherapeutic agents."}
{"id": "PMID:193182", "title": "Human breast cancer: biologically active estrogen receptor in the absence of estrogen?", "content": "The human breast cancer cell line MCF-7 does not require estrogen for growth, but paradoxically its growth is inhibited by antiestrogens. Our results show that, unlike normal target cells, MCF-7 cells carry most of their estrogen receptors in their nuclei even when these receptors are not charged with estrogens. The receptors for androgen and for progesterone, on the other hand, are localized in the cytoplasm as usual. Therefore, it is possible that the growth of these abnormal cells is stimulated by estrogen receptor in spite of the absence of the hormone and that the binding of antiestrogen molecules antagonize this stimulation.", "contents": "Human breast cancer: biologically active estrogen receptor in the absence of estrogen? The human breast cancer cell line MCF-7 does not require estrogen for growth, but paradoxically its growth is inhibited by antiestrogens. Our results show that, unlike normal target cells, MCF-7 cells carry most of their estrogen receptors in their nuclei even when these receptors are not charged with estrogens. The receptors for androgen and for progesterone, on the other hand, are localized in the cytoplasm as usual. Therefore, it is possible that the growth of these abnormal cells is stimulated by estrogen receptor in spite of the absence of the hormone and that the binding of antiestrogen molecules antagonize this stimulation."}
{"id": "PMID:193183", "title": "Cyclic GMP accumulation causes degeneration of photoreceptor cells: simulation of an inherited disease.", "content": "Guanosine 3',5'-monophosphate (cyclic GMP) metabolism in developing eye rudiments of Xenopus laevis embryos in culture is disrupted by the phosphodiesterase inhibitor isobutylmethylxanthine. At low concentrations of inhibitor the rudiments develop normally, but at higher concentrations of the inhibitor, cyclic GMP accumulates in the rudiments and the retinal photoreceptor cells degenerate selectively. The isobutylmethylxanthine-induced photoreceptor degeneration is associated with an accumulation of cyclic GMP and, in this respect, it stimulates an early biochemical defect in the inherited degenerative disease of rd mice.", "contents": "Cyclic GMP accumulation causes degeneration of photoreceptor cells: simulation of an inherited disease. Guanosine 3',5'-monophosphate (cyclic GMP) metabolism in developing eye rudiments of Xenopus laevis embryos in culture is disrupted by the phosphodiesterase inhibitor isobutylmethylxanthine. At low concentrations of inhibitor the rudiments develop normally, but at higher concentrations of the inhibitor, cyclic GMP accumulates in the rudiments and the retinal photoreceptor cells degenerate selectively. The isobutylmethylxanthine-induced photoreceptor degeneration is associated with an accumulation of cyclic GMP and, in this respect, it stimulates an early biochemical defect in the inherited degenerative disease of rd mice."}
{"id": "PMID:193184", "title": "Chlamydiae (with phages), mycoplasmas, and richettsiae in Chesapeake Bay bivalves.", "content": "Intracytoplasmic chlamydia-like organisms, some with phages, rickettsia-like organisms, and mycoplasma-like organisms have been found in clams and oysters from the Chesapeake Bay area by electron microscopy. None of these organisms have been previously detected in mollusks, nor have phages been previously observed in Chlamydia sp.", "contents": "Chlamydiae (with phages), mycoplasmas, and richettsiae in Chesapeake Bay bivalves. Intracytoplasmic chlamydia-like organisms, some with phages, rickettsia-like organisms, and mycoplasma-like organisms have been found in clams and oysters from the Chesapeake Bay area by electron microscopy. None of these organisms have been previously detected in mollusks, nor have phages been previously observed in Chlamydia sp."}
{"id": "PMID:193185", "title": "Pontine reticular formation neurons: relationship of discharge to motor activity.", "content": "The discharge correlates of pontine reticular formation units were investigated in unrestrained cats. In agreement with previous investigations using immobilized preparations, we found that these cells had high rates of activity in rapid eye movement sleep, and responded in waking to somatic, auditory, and vestibular stimuli at short latencies, many having polysensory responses and exhibiting rapid \"habituation.\" However, despite the sensory responses of these cells, most unit activity could not be explained by the presence of sensory stimuli. Intense firing occurred in association with specific movements. Units deprived of their adequate somatic, vestibular, and auditory stimuli showed undiminished discharge rates during motor activity. Discrete sensory stimuli evoked sustained unit firing only when they also evoked a motor response. We conclude that activity in pontine reticular formation neurons is more closely related to motor output than to sensory input.", "contents": "Pontine reticular formation neurons: relationship of discharge to motor activity. The discharge correlates of pontine reticular formation units were investigated in unrestrained cats. In agreement with previous investigations using immobilized preparations, we found that these cells had high rates of activity in rapid eye movement sleep, and responded in waking to somatic, auditory, and vestibular stimuli at short latencies, many having polysensory responses and exhibiting rapid \"habituation.\" However, despite the sensory responses of these cells, most unit activity could not be explained by the presence of sensory stimuli. Intense firing occurred in association with specific movements. Units deprived of their adequate somatic, vestibular, and auditory stimuli showed undiminished discharge rates during motor activity. Discrete sensory stimuli evoked sustained unit firing only when they also evoked a motor response. We conclude that activity in pontine reticular formation neurons is more closely related to motor output than to sensory input."}
{"id": "PMID:193186", "title": "Drug tolerance in biomembranes: a spin label study of the effects of ethanol.", "content": "Ethanol in vitro increased the fluidity of spin-labeled membranes from normal mice. Membranes from mice that had been subjected to long-term ethanol treatment were relatively resistant to this fluidizing effect. The data suggest that the membranes themselves had adapted to the drug, a novel form of drug tolerance.", "contents": "Drug tolerance in biomembranes: a spin label study of the effects of ethanol. Ethanol in vitro increased the fluidity of spin-labeled membranes from normal mice. Membranes from mice that had been subjected to long-term ethanol treatment were relatively resistant to this fluidizing effect. The data suggest that the membranes themselves had adapted to the drug, a novel form of drug tolerance."}
{"id": "PMID:193187", "title": "Hormone-induced cyclic guanosine monophosphate secretion from guinea pig pancreatic lobules.", "content": "Carbamylcholine (30 micronM) increased the concentration of guanosine 3',5'-monophosphate (cyclic GMP) in guinea pig pancreatic lobules about eight-to tenfold over the basal concentration in 30 seconds with a concomitant increase in the rate of amylase secretion. The concentration of cyclic GMP rapidly declined to a plateau value of about 16 percent of the peak level in 10 minutes. Cellular cyclic GMP decreased, mostly because the nucleotide was secreted into medium; cellular adenosine 3',5'-monophosphate (cyclic AMP), however did not change, nor was this nucleotide secreted into the medium. An immunocytochemical technique showed that cyclic GMP was distributed in the apical plasmalemma membrane and lumen of the pancreas. Carbamylcholine increased the cyclic GMP fluorescence in tha apical plasmalemma membrane within 30 seconds, and in zymogen granules and the plasma membrane in the apical part of acinar cells in 10 minutes. The islets of Langerhans did not show any change in cyclic GMP. Fluorescence of cyclic AMP in pancreatic lobules was not altered by carbamylcholine and was localized along the apical portion of plasmalemma and cytoplasm. Cyclic GMP  may thus participate either in the process of exocytosis or in the activation of enzymes secreted from the pancreas.", "contents": "Hormone-induced cyclic guanosine monophosphate secretion from guinea pig pancreatic lobules. Carbamylcholine (30 micronM) increased the concentration of guanosine 3',5'-monophosphate (cyclic GMP) in guinea pig pancreatic lobules about eight-to tenfold over the basal concentration in 30 seconds with a concomitant increase in the rate of amylase secretion. The concentration of cyclic GMP rapidly declined to a plateau value of about 16 percent of the peak level in 10 minutes. Cellular cyclic GMP decreased, mostly because the nucleotide was secreted into medium; cellular adenosine 3',5'-monophosphate (cyclic AMP), however did not change, nor was this nucleotide secreted into the medium. An immunocytochemical technique showed that cyclic GMP was distributed in the apical plasmalemma membrane and lumen of the pancreas. Carbamylcholine increased the cyclic GMP fluorescence in tha apical plasmalemma membrane within 30 seconds, and in zymogen granules and the plasma membrane in the apical part of acinar cells in 10 minutes. The islets of Langerhans did not show any change in cyclic GMP. Fluorescence of cyclic AMP in pancreatic lobules was not altered by carbamylcholine and was localized along the apical portion of plasmalemma and cytoplasm. Cyclic GMP  may thus participate either in the process of exocytosis or in the activation of enzymes secreted from the pancreas."}
{"id": "PMID:193188", "title": "Cytochrome c: immunofluorescent localization of the testis-specific form.", "content": "Mouse testes contain a unique form of cytochrome c. As demonstrated by the indirect immunofluorescence technique, the testis-specific cytochrome c is detectable in the primary spermatocyte and in cell types comprising the later stages of spermatogenesis. Interstitial cells, Sertoli cells, and spermatogonia contain the somatic form of cytochrome c, as does heart muscle.", "contents": "Cytochrome c: immunofluorescent localization of the testis-specific form. Mouse testes contain a unique form of cytochrome c. As demonstrated by the indirect immunofluorescence technique, the testis-specific cytochrome c is detectable in the primary spermatocyte and in cell types comprising the later stages of spermatogenesis. Interstitial cells, Sertoli cells, and spermatogonia contain the somatic form of cytochrome c, as does heart muscle."}
{"id": "PMID:193189", "title": "Cerebrospinal fluid production: stimulation by cholera toxin.", "content": "Large increases in the production of cerebrospinal fluid have been observed after the intraventricular administration of cholera toxin. Because cholera toxin stimulates adenylate cyclase, the data suggest that adenosine 3',5'-monophosphate plays a role in cerebrospinal fluid production.", "contents": "Cerebrospinal fluid production: stimulation by cholera toxin. Large increases in the production of cerebrospinal fluid have been observed after the intraventricular administration of cholera toxin. Because cholera toxin stimulates adenylate cyclase, the data suggest that adenosine 3',5'-monophosphate plays a role in cerebrospinal fluid production."}
{"id": "PMID:193191", "title": "Synapse formation between two clonal cell lines.", "content": "Clonal neuroblastoma x glioma hybrid cells frequently formed synapses with clonal mouse striated muscle cells. Clonal myotubes were similar to cultured mouse embryo myotubes with respect to acetylcholine sensitivity and other membrane properties examined. However, acetylcholine sensitivity measurements indicate that acetylcholine receptors of clonal myotubes are distributed more uniformly over the cell surface than the receptors of cultured mouse embryo myotubes.", "contents": "Synapse formation between two clonal cell lines. Clonal neuroblastoma x glioma hybrid cells frequently formed synapses with clonal mouse striated muscle cells. Clonal myotubes were similar to cultured mouse embryo myotubes with respect to acetylcholine sensitivity and other membrane properties examined. However, acetylcholine sensitivity measurements indicate that acetylcholine receptors of clonal myotubes are distributed more uniformly over the cell surface than the receptors of cultured mouse embryo myotubes."}
{"id": "PMID:193192", "title": "Gating of neuronal transmission in the hippocampus: efficacy of transmission varies with behavioral state.", "content": "Electrical stimuli were applied to the angular bundle of the freely moving rat, and the neuronal responses were recorded ipsilaterally in the dentate gyrus and the CA1 field of the hippocampus. The number of neurons responding monosynaptically in the dentate gyrus was relatively small when the animal was alert and not moving but was much greater both during slow-wave sleep and during rapid eye movement sleep. In Ca1, however, the trisynaptic population response was considerably smaller during rapid eye movement sleep and when the animal was alert than during slow-wave sleep. These findings are interpreted in terms of a set of behaviorally dependent \"neural gates\". Measurement of the synaptic current at the dentate gyrus induced monosynaptically by stimulation of the angular bundle further suggests that the mechanism by which gating occurs at this level is either a tonic inhibitory synaptic influence exerted upon the granule cells during the alert state, a tonic excitatory influence during slow-wave sleep, or both.", "contents": "Gating of neuronal transmission in the hippocampus: efficacy of transmission varies with behavioral state. Electrical stimuli were applied to the angular bundle of the freely moving rat, and the neuronal responses were recorded ipsilaterally in the dentate gyrus and the CA1 field of the hippocampus. The number of neurons responding monosynaptically in the dentate gyrus was relatively small when the animal was alert and not moving but was much greater both during slow-wave sleep and during rapid eye movement sleep. In Ca1, however, the trisynaptic population response was considerably smaller during rapid eye movement sleep and when the animal was alert than during slow-wave sleep. These findings are interpreted in terms of a set of behaviorally dependent \"neural gates\". Measurement of the synaptic current at the dentate gyrus induced monosynaptically by stimulation of the angular bundle further suggests that the mechanism by which gating occurs at this level is either a tonic inhibitory synaptic influence exerted upon the granule cells during the alert state, a tonic excitatory influence during slow-wave sleep, or both."}
{"id": "PMID:193193", "title": "The complementary role of computerized axial transmission tomography and radionuclide imaging of the brain.", "content": "Computerized axial transmission tomography and radionuclide imaging are complementary procedures, and the following recommendations are made as to their use. Where there is no real clinical suspicion of intracranial disease, either modality can be used for \"rule out\" screening; the choice can frequently be made on the basis of which modality is cheaper or more quickly available. It should be remembered that \"quicker\" is often \"cheaper\". Total cost is determined, not only by the cost of the procedure, but also the per diem costs incurred in waiting for that procedure. Thus the more expensive modality may, in effect, be cheaper if delays are shorter. Screening of the elderly patient, particularly when atrophy or communicating hydrocephalus is of clinical concern, should be by the CT method because of its ability to visualize cerebrospinal fluid spaces. When clinical signs and symptoms point to intracranial abnormality, both modalities should be utilized. If either study done first is normal, use of the other modality is mandatory. When the first study is positive with pathognomonic findings for a specific disease, which totally explains the patient's neurologic problems, the second study need not be employed. Such examples might include the fresh cerebral hemorrhage demonstrated by CT imaging, the AV malformation defined by dynamic-static radionuclide imaging, or multifocal metastatic lesions defined by either. However, when the clinical picture is not totally and satisfactorily explained by the demonstrated disease, the other modality should also be employed. Under many circumstances, neither study will be so reliable, specific, and free of false-negative or false-positive findings as to warrant ignoring the additional information potentially available from the other study.", "contents": "The complementary role of computerized axial transmission tomography and radionuclide imaging of the brain. Computerized axial transmission tomography and radionuclide imaging are complementary procedures, and the following recommendations are made as to their use. Where there is no real clinical suspicion of intracranial disease, either modality can be used for \"rule out\" screening; the choice can frequently be made on the basis of which modality is cheaper or more quickly available. It should be remembered that \"quicker\" is often \"cheaper\". Total cost is determined, not only by the cost of the procedure, but also the per diem costs incurred in waiting for that procedure. Thus the more expensive modality may, in effect, be cheaper if delays are shorter. Screening of the elderly patient, particularly when atrophy or communicating hydrocephalus is of clinical concern, should be by the CT method because of its ability to visualize cerebrospinal fluid spaces. When clinical signs and symptoms point to intracranial abnormality, both modalities should be utilized. If either study done first is normal, use of the other modality is mandatory. When the first study is positive with pathognomonic findings for a specific disease, which totally explains the patient's neurologic problems, the second study need not be employed. Such examples might include the fresh cerebral hemorrhage demonstrated by CT imaging, the AV malformation defined by dynamic-static radionuclide imaging, or multifocal metastatic lesions defined by either. However, when the clinical picture is not totally and satisfactorily explained by the demonstrated disease, the other modality should also be employed. Under many circumstances, neither study will be so reliable, specific, and free of false-negative or false-positive findings as to warrant ignoring the additional information potentially available from the other study."}
{"id": "PMID:193194", "title": "Computerized cranial tomography and radionuclide imaging in the detection of intracranial mass lesions.", "content": "Computerized cranial tomography (CCT) and radionuclide imaging (RI) of the brain are both accurate techniques for detecting intracranial mass lesions. CCT is superior in detecting low-grade gliomas, cystic lesions, parasellar tumors, and brain stem lesions. Overall, CCT detection rates are slightly higher than those with RI, but the use of iodinated contrast media with CCT increases the risk of this examination. There is a significant difference in the generally binary (positive/negative) type of information offered by RI and the more specific information offered by CCT about the pathologic nature of a lesion and its precise location. In the evaluation of patients with suspected intracranial mass lesions, CCT is generally the preferable initial diagnostic test. However, RI may still serve as a satisfactory screening examination in certain well-defined clinical situations.", "contents": "Computerized cranial tomography and radionuclide imaging in the detection of intracranial mass lesions. Computerized cranial tomography (CCT) and radionuclide imaging (RI) of the brain are both accurate techniques for detecting intracranial mass lesions. CCT is superior in detecting low-grade gliomas, cystic lesions, parasellar tumors, and brain stem lesions. Overall, CCT detection rates are slightly higher than those with RI, but the use of iodinated contrast media with CCT increases the risk of this examination. There is a significant difference in the generally binary (positive/negative) type of information offered by RI and the more specific information offered by CCT about the pathologic nature of a lesion and its precise location. In the evaluation of patients with suspected intracranial mass lesions, CCT is generally the preferable initial diagnostic test. However, RI may still serve as a satisfactory screening examination in certain well-defined clinical situations."}
{"id": "PMID:193197", "title": "Hyperkalemia due to selective hypoaldosteronism.", "content": "Hyperkalemia secondary to hyporeninemic hypoaldosteronism with a normal glucocorticoid function was diagnosed in a 47-year-old man with moderate renal insufficiency. Mineralocorticoid administration corrected the hyperkalemia. A probable explanation for hyporeninemia and hypoaldosteronism in this syndrome is that the primary defect is an inability to release renin and the resultant angiotensin deficiency leads to an aldosterone deficiency.", "contents": "Hyperkalemia due to selective hypoaldosteronism. Hyperkalemia secondary to hyporeninemic hypoaldosteronism with a normal glucocorticoid function was diagnosed in a 47-year-old man with moderate renal insufficiency. Mineralocorticoid administration corrected the hyperkalemia. A probable explanation for hyporeninemia and hypoaldosteronism in this syndrome is that the primary defect is an inability to release renin and the resultant angiotensin deficiency leads to an aldosterone deficiency."}
{"id": "PMID:193200", "title": "Current chemotherapy of schistosomiasis japonica in the Philippines.", "content": "For the past several decades, the drug being used for the treatment of schistosomiasis in the Philippines has been Stibophen. It is administered intramuscularly at a dose of 1 ml per 10 kg body weight with a maximum of 5 ml every other day after 2 initial daily smaller sensitivity doses at a total dose of 45 to 70 ml fof adult patients. In recent years, a number of drugs for the treatment of schistosomiasis have been developed. These were evaluated clinically either in the hospital or in field trials in Leyte. Unfortunately, none of these were found to be suitable for mass treatment on account of toxicity to prolonged course of treatment. In view of the pressing need for a safe and effective schistosomicidal agent, the search for a better drug is imperative.", "contents": "Current chemotherapy of schistosomiasis japonica in the Philippines. For the past several decades, the drug being used for the treatment of schistosomiasis in the Philippines has been Stibophen. It is administered intramuscularly at a dose of 1 ml per 10 kg body weight with a maximum of 5 ml every other day after 2 initial daily smaller sensitivity doses at a total dose of 45 to 70 ml fof adult patients. In recent years, a number of drugs for the treatment of schistosomiasis have been developed. These were evaluated clinically either in the hospital or in field trials in Leyte. Unfortunately, none of these were found to be suitable for mass treatment on account of toxicity to prolonged course of treatment. In view of the pressing need for a safe and effective schistosomicidal agent, the search for a better drug is imperative."}
{"id": "PMID:193201", "title": "Drug trial of Schistosoma japonicum enfection in Indonesia.", "content": "A limited drug trial was carried out on 42 cases with schistosomiasis japonica from an endemic area of Central Sulawesi. The drugs used were niridazole and stibophen. The effects of treatment were reported and discussed. The results of this study offer promise for treating S. japonicum infection in Central Sulawesi on a larger scale.", "contents": "Drug trial of Schistosoma japonicum enfection in Indonesia. A limited drug trial was carried out on 42 cases with schistosomiasis japonica from an endemic area of Central Sulawesi. The drugs used were niridazole and stibophen. The effects of treatment were reported and discussed. The results of this study offer promise for treating S. japonicum infection in Central Sulawesi on a larger scale."}
{"id": "PMID:193204", "title": "Comparison of some methods for the detection of antigen-antibody reactions in amoebiasis.", "content": "The indirect hemagglutination test (IHA) and counterimmuno-electrophoresis (CIE) were used to test for antibodies to Entamoeba histolytica in human sera using antigens from axenic cultures of the HK9 strain. Correlation between the test was excellent with most sera from patients with amoebiasis demonstrating precipitin lines by CIE at IHA titers considered diagnostically positive, larger than or equal to 1:128. Precipitin reactions with positive sera were also compared by CIE, immunoelectrophoresis (IEP) and two-dimensional electrophoresis is (2D-IEP). The greatest number of antigen-antibody components were demonstrated by 2D-IEP. Further studies utilizing 2D-IEP should be of value in the antigenic analysis of E. histolytica.", "contents": "Comparison of some methods for the detection of antigen-antibody reactions in amoebiasis. The indirect hemagglutination test (IHA) and counterimmuno-electrophoresis (CIE) were used to test for antibodies to Entamoeba histolytica in human sera using antigens from axenic cultures of the HK9 strain. Correlation between the test was excellent with most sera from patients with amoebiasis demonstrating precipitin lines by CIE at IHA titers considered diagnostically positive, larger than or equal to 1:128. Precipitin reactions with positive sera were also compared by CIE, immunoelectrophoresis (IEP) and two-dimensional electrophoresis is (2D-IEP). The greatest number of antigen-antibody components were demonstrated by 2D-IEP. Further studies utilizing 2D-IEP should be of value in the antigenic analysis of E. histolytica."}
{"id": "PMID:193205", "title": "Future geriatric needs in South Africa. Hospital and teaching aspects.", "content": "Noteworthy factors in geriatric care, derived from experience in a geriatric clinic, are that symptoms are often wrongly attributed to the ageing process; the aged are often overtreated and subjected to unnecessary diagnostic procedures; and functional abilities of the elderly and social factors are important in planning comprehensive care for the aged. To render total care the services of a visiting sister attached to the clinic are an absolute necessity. The elderly are often prematurely discharged from hospital. The combination of multiple pathology, functional derangement and social factors necessitates a period of aftercare which entails physiotherapy, occupational therapy and the services of a social worker. Medical students, nurses, students in social work, psysiotherapists, and occupational therapists should be enlightened on gerontology and geriatrics during their undergraduate years.", "contents": "Future geriatric needs in South Africa. Hospital and teaching aspects. Noteworthy factors in geriatric care, derived from experience in a geriatric clinic, are that symptoms are often wrongly attributed to the ageing process; the aged are often overtreated and subjected to unnecessary diagnostic procedures; and functional abilities of the elderly and social factors are important in planning comprehensive care for the aged. To render total care the services of a visiting sister attached to the clinic are an absolute necessity. The elderly are often prematurely discharged from hospital. The combination of multiple pathology, functional derangement and social factors necessitates a period of aftercare which entails physiotherapy, occupational therapy and the services of a social worker. Medical students, nurses, students in social work, psysiotherapists, and occupational therapists should be enlightened on gerontology and geriatrics during their undergraduate years."}
{"id": "PMID:193214", "title": "Feto-maternal amino acid patterns and cyclic AMP in the human placenta with abnormal pregnancies, particularly with SFD.", "content": "To clarify the causes of SFD from the view-point of placental function, investigations were made on feto-maternal amino acid circumstances and on how cyclic AMP behaves in the placenta, particularly in relation to the transport of amino acid across the placenta. Amino acids were measured by gas liquid chromatography (hydrogen-flame ion detector), c-AMP by the binding protein method, adenyl cyclase activity by Krishna's method, and proteins by Lowry's method. Results show: (1) The levels of maternal amino acids were indistinctive between the SFD group and the normal pregnancy group. (2) The feto-maternal ratio of amino acid concentrations (f/m ratio) was lower in the SFD group than in the normal control. (3) The level of c-AMP in the placenta was lower in the SFD group than in the control. (4) The lower level of placenta c-AMP in the SFD placenta seems partly attributable to the decreased adenyl cyclase activity. (5) There was a positive correlation (gamma=0.61) between the content of c-AMP in the placenta and the f/m ratio of amino acid concentrations. These findings suggest a decline in placental active transport of acids in SFD; adenyl cyclase and c-AMP in the placenta presumably play a key role in such course.", "contents": "Feto-maternal amino acid patterns and cyclic AMP in the human placenta with abnormal pregnancies, particularly with SFD. To clarify the causes of SFD from the view-point of placental function, investigations were made on feto-maternal amino acid circumstances and on how cyclic AMP behaves in the placenta, particularly in relation to the transport of amino acid across the placenta. Amino acids were measured by gas liquid chromatography (hydrogen-flame ion detector), c-AMP by the binding protein method, adenyl cyclase activity by Krishna's method, and proteins by Lowry's method. Results show: (1) The levels of maternal amino acids were indistinctive between the SFD group and the normal pregnancy group. (2) The feto-maternal ratio of amino acid concentrations (f/m ratio) was lower in the SFD group than in the normal control. (3) The level of c-AMP in the placenta was lower in the SFD group than in the control. (4) The lower level of placenta c-AMP in the SFD placenta seems partly attributable to the decreased adenyl cyclase activity. (5) There was a positive correlation (gamma=0.61) between the content of c-AMP in the placenta and the f/m ratio of amino acid concentrations. These findings suggest a decline in placental active transport of acids in SFD; adenyl cyclase and c-AMP in the placenta presumably play a key role in such course."}
{"id": "PMID:193215", "title": "Biochemical differences between human malignant and benign insulinoma tissues.", "content": "Five cases of malignant insulinoma and 2 cases of benign insulinoma were studied lipid-chemically. Tissues were collected by surgical operation or biopsy under peritoneoscopy. The total lipid was extracted from each tissue, and one part of each total lipid was separated into phospholipid, triglyceride and other lipid fractions by a thin-layer chromatography (TLC) on silica gel. The fatty acid composition and fatty acid content of each lipid fraction were measured by a gas-liquid chromatography (GLC). The most remarkable difference between malignant and benign isulinoma tissues was a higher percentage value of eicosatrienoic acid in the phospholipid of malignant insulinoma tissues when compared with that of non-malignant insulinoma tissues; the values mentioned above distributed between 9.82 and 3.32 in 5 malignant cases, but were 2.89 and 2.57 in 2 benign cases. Those changes in the phospholipid fatty acid composition of malignant insulinoma tissues may represent one of the mechanisms of malignant growth in the malignant neoplastic tissue.", "contents": "Biochemical differences between human malignant and benign insulinoma tissues. Five cases of malignant insulinoma and 2 cases of benign insulinoma were studied lipid-chemically. Tissues were collected by surgical operation or biopsy under peritoneoscopy. The total lipid was extracted from each tissue, and one part of each total lipid was separated into phospholipid, triglyceride and other lipid fractions by a thin-layer chromatography (TLC) on silica gel. The fatty acid composition and fatty acid content of each lipid fraction were measured by a gas-liquid chromatography (GLC). The most remarkable difference between malignant and benign isulinoma tissues was a higher percentage value of eicosatrienoic acid in the phospholipid of malignant insulinoma tissues when compared with that of non-malignant insulinoma tissues; the values mentioned above distributed between 9.82 and 3.32 in 5 malignant cases, but were 2.89 and 2.57 in 2 benign cases. Those changes in the phospholipid fatty acid composition of malignant insulinoma tissues may represent one of the mechanisms of malignant growth in the malignant neoplastic tissue."}
{"id": "PMID:193221", "title": "Plasmodium chabaudi-infection of mice: specific activities of erythrocyte membrane-associated enzymes and patterns of proteins and glycoproteins of erythrocyte membrane preparations.", "content": "Membrane preparations of erythrocytes from normal and P. chabaudi-infected mice and membrane preparations of P. chabaudi-infected and uninfected erythrocytes from infected mice and separated by zonal centrifugation were characterized by the pattern of proteins and extracted glycoproteins obtained by SDS-polyacrylamide gel electrophoresis and by the specific activities of membrane associated enzymes. The protein pattern of the membrane preparation of infected erythrocytes showed similar differences from membrane preparations of normal erythrocytes as those described by Weidekamm et al. for P. berghei. The pattern of glycoproteins extracted by the chloroform-methanol method showed characteristic differences as compared to the controls. A new band (PASi) with a molecular weight of about 165,000 corresponds with the protein band IIa. In membrane preparations of normal erythrocytes and of nonparasitized erythrocytes separated from parasitized erythrocytes by zonal centrifugation was no difference in specific activities of ATPase, adenylate kinase and acetylcholinesterase. Adenylate kinase activity was markedly increased and acetyl-cholinesterase activity was slightly increased in membrane preparations of infected cells. Specific activities of ATPase of membrane preparations of normal and parasitized erythrocytes did not show significant differences. There was a decrease in enzyme activity of ATPase and an increase of acetylcholinesterase in Triton X 100 containing samples. Specific activities of an acid phosphatase were lower in membrane preparations of parasitized cells than in the controls.", "contents": "Plasmodium chabaudi-infection of mice: specific activities of erythrocyte membrane-associated enzymes and patterns of proteins and glycoproteins of erythrocyte membrane preparations. Membrane preparations of erythrocytes from normal and P. chabaudi-infected mice and membrane preparations of P. chabaudi-infected and uninfected erythrocytes from infected mice and separated by zonal centrifugation were characterized by the pattern of proteins and extracted glycoproteins obtained by SDS-polyacrylamide gel electrophoresis and by the specific activities of membrane associated enzymes. The protein pattern of the membrane preparation of infected erythrocytes showed similar differences from membrane preparations of normal erythrocytes as those described by Weidekamm et al. for P. berghei. The pattern of glycoproteins extracted by the chloroform-methanol method showed characteristic differences as compared to the controls. A new band (PASi) with a molecular weight of about 165,000 corresponds with the protein band IIa. In membrane preparations of normal erythrocytes and of nonparasitized erythrocytes separated from parasitized erythrocytes by zonal centrifugation was no difference in specific activities of ATPase, adenylate kinase and acetylcholinesterase. Adenylate kinase activity was markedly increased and acetyl-cholinesterase activity was slightly increased in membrane preparations of infected cells. Specific activities of ATPase of membrane preparations of normal and parasitized erythrocytes did not show significant differences. There was a decrease in enzyme activity of ATPase and an increase of acetylcholinesterase in Triton X 100 containing samples. Specific activities of an acid phosphatase were lower in membrane preparations of parasitized cells than in the controls."}
{"id": "PMID:193217", "title": "Apolipoprotein B (apoB) retention in atherosclerotic intracranial arteries.", "content": "Low (LDL) and very low (VLDL) density lipoproteins retained in grossly normal and atherosclerotic human intracranial arteries have been quantitated using an electro-immunoassay directed against apolipoprotein B (apoB), the major protein of these two lipoprotein fractions. Buffer-homogenates of grossly normal arteries contained apoB amounts ranging from less than 0.04 to 1.58 microng/mg tissue dry weight, while those of atherosclerotic plaques gave values ranging from 0.80 to 3.9 microng per mg tissue dry weight. These results were consistent with immunofluorescence studies localizing apoB in these arteries. Plaques also contained a remaining fraction of tightly-bound apoB as evidenced by positive immunofluorescence in sections of pellets from buffer homogenates. This was in contrast to the negative results from grossly normal arteries. These results would suggest that retention of apoB by intracranial arteries correlates positively with vessel lesions. Arterial apoB is present in both grossly normal regions and plaques in a loosely-bound form, possibly representing intact lipoprotein. ApoB is also present in a tightly-bound form in plaques.", "contents": "Apolipoprotein B (apoB) retention in atherosclerotic intracranial arteries. Low (LDL) and very low (VLDL) density lipoproteins retained in grossly normal and atherosclerotic human intracranial arteries have been quantitated using an electro-immunoassay directed against apolipoprotein B (apoB), the major protein of these two lipoprotein fractions. Buffer-homogenates of grossly normal arteries contained apoB amounts ranging from less than 0.04 to 1.58 microng/mg tissue dry weight, while those of atherosclerotic plaques gave values ranging from 0.80 to 3.9 microng per mg tissue dry weight. These results were consistent with immunofluorescence studies localizing apoB in these arteries. Plaques also contained a remaining fraction of tightly-bound apoB as evidenced by positive immunofluorescence in sections of pellets from buffer homogenates. This was in contrast to the negative results from grossly normal arteries. These results would suggest that retention of apoB by intracranial arteries correlates positively with vessel lesions. Arterial apoB is present in both grossly normal regions and plaques in a loosely-bound form, possibly representing intact lipoprotein. ApoB is also present in a tightly-bound form in plaques."}
{"id": "PMID:193218", "title": "Dibutyryl cyclic adenosine monophosphate effects in the ischemic-hypoxic cat.", "content": "The effects of dibutyryl cyclic adenosine monophosphate (dB-cAMP) were studied in fifty cats, twenty anesthetized with pentobarbital and thirty with halothane. Nasopharyngeal temperature and Paco2 were maintained at normal values. Somatosensory evoked response was monitored and used as an indicator of cerebral cortical function. Ischemic hypoxic injury was produced by an orthopedic tourniquet snugly applied around the animal's neck and inflated for a period of fifteen minutes. This method produces a reliable and reproducible injury. Times for recovery of the evoked response to 10% of control value, as well as immediate and long-term animal survival, were noted. The dBcAMP was administered at the end of the hypoxic insult. Treated animals recovered the evoked response earlier than the untreated controls and had better immediate and long-term survival rates.", "contents": "Dibutyryl cyclic adenosine monophosphate effects in the ischemic-hypoxic cat. The effects of dibutyryl cyclic adenosine monophosphate (dB-cAMP) were studied in fifty cats, twenty anesthetized with pentobarbital and thirty with halothane. Nasopharyngeal temperature and Paco2 were maintained at normal values. Somatosensory evoked response was monitored and used as an indicator of cerebral cortical function. Ischemic hypoxic injury was produced by an orthopedic tourniquet snugly applied around the animal's neck and inflated for a period of fifteen minutes. This method produces a reliable and reproducible injury. Times for recovery of the evoked response to 10% of control value, as well as immediate and long-term animal survival, were noted. The dBcAMP was administered at the end of the hypoxic insult. Treated animals recovered the evoked response earlier than the untreated controls and had better immediate and long-term survival rates."}
{"id": "PMID:193225", "title": "Helium pressure alteration of function in squid giant synapse.", "content": "The squid giant synapse, which permits intracellular electrical measurements in a single, excitatory synapse, was exposed to helium pressures up to 204 atm. By stimulating presynaptically and recording postsynaptically with an intracellular electrode it was found that pressure alters, but does not prevent, synaptic transmission of action potentials. Synaptically transmitted action potentials are prolonged in the same way as in the directly stimulated axon. However, slowing of the excitatory postsynaptic potential and marked increases in synaptic fatigue were observed at pressures as low as 35 atm. These changes may contribute to high pressure nervous effects by interfering with information transfer within the nervous system.", "contents": "Helium pressure alteration of function in squid giant synapse. The squid giant synapse, which permits intracellular electrical measurements in a single, excitatory synapse, was exposed to helium pressures up to 204 atm. By stimulating presynaptically and recording postsynaptically with an intracellular electrode it was found that pressure alters, but does not prevent, synaptic transmission of action potentials. Synaptically transmitted action potentials are prolonged in the same way as in the directly stimulated axon. However, slowing of the excitatory postsynaptic potential and marked increases in synaptic fatigue were observed at pressures as low as 35 atm. These changes may contribute to high pressure nervous effects by interfering with information transfer within the nervous system."}
{"id": "PMID:193223", "title": "Herpes simplex virus nuclear nonvirion antigens detected by anticomplement immunofluorescence.", "content": "The finding of a nuclear antigen by anticomplement immunofluorescence in cells treated with cytosine-arabinoside after infection of Herpes Simplex Virus (HSV), opens a new approach to the problem of the role of this virus in certain human cancers. Complement-fixing tests of HSV markers with cancer and control human sera as well as with hyperimmune guinea pig antisera are discussed, suggesting another parameter for studies of squamous cell carcinomas. The finding of HSV antigens in selected tumors as the expression of repressed viral genome proves a continuing release of virus specific message and supports the important role of the virus in the development of the tumor.", "contents": "Herpes simplex virus nuclear nonvirion antigens detected by anticomplement immunofluorescence. The finding of a nuclear antigen by anticomplement immunofluorescence in cells treated with cytosine-arabinoside after infection of Herpes Simplex Virus (HSV), opens a new approach to the problem of the role of this virus in certain human cancers. Complement-fixing tests of HSV markers with cancer and control human sera as well as with hyperimmune guinea pig antisera are discussed, suggesting another parameter for studies of squamous cell carcinomas. The finding of HSV antigens in selected tumors as the expression of repressed viral genome proves a continuing release of virus specific message and supports the important role of the virus in the development of the tumor."}
{"id": "PMID:193224", "title": "Herpes simplex virus tumor-associated antigens in cancer patients.", "content": "Data are reported on the HSV nonstructural antigens detected in GPK and RK cells after infection with the same strain of virus. Both the HSV types 1 and 2 NV antigens consist of more than one component for which the immunized guinea pigs produce distinct antibodies. It was possible to separate by PAGE, HSV-induced markers not only from cells undergoing lytic infection by the virus but also from viable cells from squamous cell carcinoma of the head and neck and the urogenital tract. These fractions were tested with sera from cancer patients, and the percentages of their CF reactivity are reported. The specificity of the antibody to the antigen from the cancer cells was less high than that of the antibody to the antigen from HSV-infected cells. It is suggested that the use of these PAGE separate antigens would eliminate the need for removal of the virion antibody from the cancer sera prior to testing them for the NV-specific antibody.", "contents": "Herpes simplex virus tumor-associated antigens in cancer patients. Data are reported on the HSV nonstructural antigens detected in GPK and RK cells after infection with the same strain of virus. Both the HSV types 1 and 2 NV antigens consist of more than one component for which the immunized guinea pigs produce distinct antibodies. It was possible to separate by PAGE, HSV-induced markers not only from cells undergoing lytic infection by the virus but also from viable cells from squamous cell carcinoma of the head and neck and the urogenital tract. These fractions were tested with sera from cancer patients, and the percentages of their CF reactivity are reported. The specificity of the antibody to the antigen from the cancer cells was less high than that of the antibody to the antigen from HSV-infected cells. It is suggested that the use of these PAGE separate antigens would eliminate the need for removal of the virion antibody from the cancer sera prior to testing them for the NV-specific antibody."}
{"id": "PMID:193233", "title": "[Obtaining pig pulmonary macrophages for the cultivation of swine cytomegaloviruses].", "content": "A method of obtaining and cultivating pig pulmonary macrophages (PPM) is described and documented. The results obtained with its use in the cultivation of pig cytomegalovirus of the ADRI-1 reference strain are shown. In PPM cell cultures, the virus was demonstrated cytologically cytologically and by electron microscopy. After 18 passages on cell cultures, the virus, applied intranasally, infectious to colostrum.", "contents": "[Obtaining pig pulmonary macrophages for the cultivation of swine cytomegaloviruses]. A method of obtaining and cultivating pig pulmonary macrophages (PPM) is described and documented. The results obtained with its use in the cultivation of pig cytomegalovirus of the ADRI-1 reference strain are shown. In PPM cell cultures, the virus was demonstrated cytologically cytologically and by electron microscopy. After 18 passages on cell cultures, the virus, applied intranasally, infectious to colostrum."}
{"id": "PMID:193234", "title": "Allergy in cattle after foot-and-mouth disease vaccination.", "content": "BHK cell derivatives, saponin and aluminium hydroxide, all of which are commonly present in foot-and-mouth disease vaccines, were injected subcutaneously into 10 cattle and the serum levels of anti-BHK reagins and passive haemagglutinating antibodies were followed. The reaginic antibodies rose to a peak titre one to two weeks after the stimuli and waned during the third week. They had a serum half life of about three days, assuming exponential decay, and were generally undetectable four weeks after last contact with antigen. Passive haemagglutinins were slower to develop and two or more stimuli were usually required to produce detectable antibody levels. They were also slower to subside and were demonstrable for at least 10 weeks after last contact with antigen in most cases. Clinical reactions provoked by the intradermal injection of lysate into sensitised cattle were not correlated with the serum reagin or passive haemagglutinin levels or their ratio to one another at time of the reactions. The reasons for this are discussed.", "contents": "Allergy in cattle after foot-and-mouth disease vaccination. BHK cell derivatives, saponin and aluminium hydroxide, all of which are commonly present in foot-and-mouth disease vaccines, were injected subcutaneously into 10 cattle and the serum levels of anti-BHK reagins and passive haemagglutinating antibodies were followed. The reaginic antibodies rose to a peak titre one to two weeks after the stimuli and waned during the third week. They had a serum half life of about three days, assuming exponential decay, and were generally undetectable four weeks after last contact with antigen. Passive haemagglutinins were slower to develop and two or more stimuli were usually required to produce detectable antibody levels. They were also slower to subside and were demonstrable for at least 10 weeks after last contact with antigen in most cases. Clinical reactions provoked by the intradermal injection of lysate into sensitised cattle were not correlated with the serum reagin or passive haemagglutinin levels or their ratio to one another at time of the reactions. The reasons for this are discussed."}
{"id": "PMID:193237", "title": "[Effect of chemical modifiers on the antigen-binding capacity of antibodies].", "content": "The effect was followed up of the chemical modifications \"carbamylation\" and \"benzylation\" on the antigen-fixing activity of the foot-and-mouth disease immunoglobulins G and M. The chemical agents used - potassium cyanate and 2-hydroxi-5-nitrobenzylbromide--modified a considerable number of side lysine chains and tryptophane radicals, however, had no effect on the precipitation activity of the foot-and-mouth disease antibodies IgG and IgM manifested with the respective antigens. The lowered ability of the modified (to a higher degree) antibodies to form precipitations with the homologous virus was due to secondary reactions between the two components of the system, the functional groups of the active center remaining intact. The higher affinity of the IgM antibody to the homologous antigen was due to its polyvalent capacity (as compared to the bivalent immunoglobulin G).", "contents": "[Effect of chemical modifiers on the antigen-binding capacity of antibodies]. The effect was followed up of the chemical modifications \"carbamylation\" and \"benzylation\" on the antigen-fixing activity of the foot-and-mouth disease immunoglobulins G and M. The chemical agents used - potassium cyanate and 2-hydroxi-5-nitrobenzylbromide--modified a considerable number of side lysine chains and tryptophane radicals, however, had no effect on the precipitation activity of the foot-and-mouth disease antibodies IgG and IgM manifested with the respective antigens. The lowered ability of the modified (to a higher degree) antibodies to form precipitations with the homologous virus was due to secondary reactions between the two components of the system, the functional groups of the active center remaining intact. The higher affinity of the IgM antibody to the homologous antigen was due to its polyvalent capacity (as compared to the bivalent immunoglobulin G)."}
{"id": "PMID:193238", "title": "[Study of foot-and-mouth disease virus inhibitors in cell cultures and experimental animals].", "content": "Studied was the inhibiting action of some synthetic agents conditionally denoted No. 3 (benzamidazol), No. 76, and No. 78 (imidazolins) on the reproduction of the foot-and-mouth disease virus in cell cultures, newborn mice and guinea pigs. It was irrefutably demonstrated that all three agents produce an inhibiting effect on the virus. This effect was enhanced by the combined use of these inhibitors. It was found that best effect on the virus' replication produced the combination of agent No. 3 and some of the other two inhibitors. Discussed is the mechanism of action of these compounds.", "contents": "[Study of foot-and-mouth disease virus inhibitors in cell cultures and experimental animals]. Studied was the inhibiting action of some synthetic agents conditionally denoted No. 3 (benzamidazol), No. 76, and No. 78 (imidazolins) on the reproduction of the foot-and-mouth disease virus in cell cultures, newborn mice and guinea pigs. It was irrefutably demonstrated that all three agents produce an inhibiting effect on the virus. This effect was enhanced by the combined use of these inhibitors. It was found that best effect on the virus' replication produced the combination of agent No. 3 and some of the other two inhibitors. Discussed is the mechanism of action of these compounds."}
{"id": "PMID:193239", "title": "[Effect of somatotropic hormone on certain indices related to carbohydrate and fat metabolism in sheep].", "content": "Investigated was the effect of the somatotropic hormone (STH) at doses of 0.3 mg/kg and 1 mg/kg liveweight on the amount of insulin, glucose, and free fatty acids (FFA) in the serum up to the 12th hour following treatment. The activity of glucose-6-phosphatase and the amount of glycogen were studied in tissue samples taken through biopsy of the liver at the 2nd, 4th, 6th, and 8th hour after treatment with STH. The content of blood sugar decreased, and that of insulin increased in the course of one hour following treatment. The values shown by FFA first dropped (at the end of the 1st hour), and then rose by the 6th hour after treatment. The amount of glycogen and the activity of glucose-6-phosphatase increased at the 6th hour following treatment with STH. The variations shown by the investigated indices depend on the size of the STH doses.", "contents": "[Effect of somatotropic hormone on certain indices related to carbohydrate and fat metabolism in sheep]. Investigated was the effect of the somatotropic hormone (STH) at doses of 0.3 mg/kg and 1 mg/kg liveweight on the amount of insulin, glucose, and free fatty acids (FFA) in the serum up to the 12th hour following treatment. The activity of glucose-6-phosphatase and the amount of glycogen were studied in tissue samples taken through biopsy of the liver at the 2nd, 4th, 6th, and 8th hour after treatment with STH. The content of blood sugar decreased, and that of insulin increased in the course of one hour following treatment. The values shown by FFA first dropped (at the end of the 1st hour), and then rose by the 6th hour after treatment. The amount of glycogen and the activity of glucose-6-phosphatase increased at the 6th hour following treatment with STH. The variations shown by the investigated indices depend on the size of the STH doses."}
{"id": "PMID:193240", "title": "[Action of actidione on the multiplication of Aujeszky's disease virus].", "content": "Studied was the effect of actidione on the propagation of the Aujeszky's disease virus (strains 2,7,10--virulent,, and strain MK--avirulent virus mutant). It was found that at a concentration of 2 microng/cm3 actidione discontinues the reproduction of the most virulent strain 2 when the antibiotic was added immediately after the adsorption of the virus on the cells. The decrease in the virulence of the virus strain was associated with the decrease in the concentration of the antibiotic needed for the inhibition of its propagation. Thus, the reproduction of the more slightly virulent strain 10 was fully inhibited at actidione concentration of 0.75 microng/cm3, while that of the avirulent strain MK was discontinued at 0.4 microng/cm3. The preliminary cultivation of the cells with 1 microng/cm3 actidione for 24 hours and the adsorption of the virus on the cells jointly with actidione showed no effect on the vitality of the virus particles.", "contents": "[Action of actidione on the multiplication of Aujeszky's disease virus]. Studied was the effect of actidione on the propagation of the Aujeszky's disease virus (strains 2,7,10--virulent,, and strain MK--avirulent virus mutant). It was found that at a concentration of 2 microng/cm3 actidione discontinues the reproduction of the most virulent strain 2 when the antibiotic was added immediately after the adsorption of the virus on the cells. The decrease in the virulence of the virus strain was associated with the decrease in the concentration of the antibiotic needed for the inhibition of its propagation. Thus, the reproduction of the more slightly virulent strain 10 was fully inhibited at actidione concentration of 0.75 microng/cm3, while that of the avirulent strain MK was discontinued at 0.4 microng/cm3. The preliminary cultivation of the cells with 1 microng/cm3 actidione for 24 hours and the adsorption of the virus on the cells jointly with actidione showed no effect on the vitality of the virus particles."}
{"id": "PMID:193241", "title": "[Demonstration and type determination of Clostridium perfringens isolated from meat semipreserves].", "content": "Investigated were a total of 92 samples of pasteurized cans of different batches. Six strains of Clostridium perfringens were isolated from a sample of pasteurized ham. To demonstrate a toxin and present its type differentiation a strain was investigated with the use of dermonecrotic test after Williams along with the cross toxin neutralization after the internationally accepted method, and the neutralization of the lecithinase activity after Williams. The use of native toxins at the type differentiation of slightly toxigenic strains of Clostridium perfringens isolated from food products proved inappropriate. The production of dry toxin and the application of cross toxinneutralization proved to be most suitable in the typing of such strains. The type differentiation carried out as described above showed that the studied strain belonged to type A.", "contents": "[Demonstration and type determination of Clostridium perfringens isolated from meat semipreserves]. Investigated were a total of 92 samples of pasteurized cans of different batches. Six strains of Clostridium perfringens were isolated from a sample of pasteurized ham. To demonstrate a toxin and present its type differentiation a strain was investigated with the use of dermonecrotic test after Williams along with the cross toxin neutralization after the internationally accepted method, and the neutralization of the lecithinase activity after Williams. The use of native toxins at the type differentiation of slightly toxigenic strains of Clostridium perfringens isolated from food products proved inappropriate. The production of dry toxin and the application of cross toxinneutralization proved to be most suitable in the typing of such strains. The type differentiation carried out as described above showed that the studied strain belonged to type A."}
{"id": "PMID:193242", "title": "[Study of the immunity in swine vaccinated with type C anti-foot-and-mouth disease vaccine].", "content": "Experiments were carried out to adapt a cell culture strain of the foot-and-mouth disease virus, type C, to the organism of susceptible pigs. It was established that 4 to 5 passages are needed to adapt the virus, all treated animals showing the symptoms of the disease from the 24 hour following infection which assumed a generalized course. In determining the index of protection (P) of a given F.M.D. vaccine through challenging immunized pigs its value proves to be 4.5. It is stressed that this is a suitable and economic method to evaluate the immunogenic properties of F.M.D. vaccines for pigs.", "contents": "[Study of the immunity in swine vaccinated with type C anti-foot-and-mouth disease vaccine]. Experiments were carried out to adapt a cell culture strain of the foot-and-mouth disease virus, type C, to the organism of susceptible pigs. It was established that 4 to 5 passages are needed to adapt the virus, all treated animals showing the symptoms of the disease from the 24 hour following infection which assumed a generalized course. In determining the index of protection (P) of a given F.M.D. vaccine through challenging immunized pigs its value proves to be 4.5. It is stressed that this is a suitable and economic method to evaluate the immunogenic properties of F.M.D. vaccines for pigs."}
{"id": "PMID:193243", "title": "[Participation of Aujeszky's disease virus in the respiratory diseases of swine].", "content": "Clinical, virologic and seroligic investigations on vaccinated and unvaccinated pigs fattened on two farms with a record of a stationary Aujeszky's disease infection were carried out. Aujeszky's virus was isolated from the lungs of all pigs and partially of other viscera of some of the animals. The serologic studies revealed the dynamics of the antibody titer reise which spoke of the development of an infectious process. The clinical signs observed along with the morphologic changes characteristic of pneumonia, coupled with the advancement of the Aujeszky's disease infection demonstrated that on stationary fattening pig farms Aujeszky's disease assumed the course of a respiratory affection. The discripancy between the results obtained with vaccinated and unvaccinated animals, which were negligible on one of the farms and considerable on the other, was due to variations in the intensity of the infection as well as to the level of passive immunity.", "contents": "[Participation of Aujeszky's disease virus in the respiratory diseases of swine]. Clinical, virologic and seroligic investigations on vaccinated and unvaccinated pigs fattened on two farms with a record of a stationary Aujeszky's disease infection were carried out. Aujeszky's virus was isolated from the lungs of all pigs and partially of other viscera of some of the animals. The serologic studies revealed the dynamics of the antibody titer reise which spoke of the development of an infectious process. The clinical signs observed along with the morphologic changes characteristic of pneumonia, coupled with the advancement of the Aujeszky's disease infection demonstrated that on stationary fattening pig farms Aujeszky's disease assumed the course of a respiratory affection. The discripancy between the results obtained with vaccinated and unvaccinated animals, which were negligible on one of the farms and considerable on the other, was due to variations in the intensity of the infection as well as to the level of passive immunity."}
{"id": "PMID:193244", "title": "[Ultrastructure of liver damage in chronic vinyl chloride intoxication (author's transl)].", "content": "Liver biopsies taken from 15 workers at a PVC-producing factory were examined by electron microscopy. The hepatocytes showed focal hydropic swelling, disseminated toxic steatosis, peculiar para-crystalline inclusions in enlarged mitochondria, focal cytoplasmic degradations, and occasional single cell necroses. These regressive changes were more prominent in cases with a shorter interval of non-exposure prior to the biopsy. Further, a focal compensatory hyperplasia of the smooth endoplasmatic reticulum was found. With increase of the non-exposure time interval, a regression of the degree of steatosis as well as an age-independent excessive lipofuscin deposition was seen in the hepatocytes. Apparently, these are sequelae of increased autophagia of lipids and increased lipid oxidation by the vinylchloride. In the sinusoids, activation, enlargement and proliferation of Kupffer cells was noted. The tendency of these cells to proliferate is apparently caused by the cancerogenic stimulation by vinylchloride. The prominent hyperplasia of lipocytes is probably connected with the deposition of collagen and the peculiar perisinusoidal fibrosis.", "contents": "[Ultrastructure of liver damage in chronic vinyl chloride intoxication (author's transl)]. Liver biopsies taken from 15 workers at a PVC-producing factory were examined by electron microscopy. The hepatocytes showed focal hydropic swelling, disseminated toxic steatosis, peculiar para-crystalline inclusions in enlarged mitochondria, focal cytoplasmic degradations, and occasional single cell necroses. These regressive changes were more prominent in cases with a shorter interval of non-exposure prior to the biopsy. Further, a focal compensatory hyperplasia of the smooth endoplasmatic reticulum was found. With increase of the non-exposure time interval, a regression of the degree of steatosis as well as an age-independent excessive lipofuscin deposition was seen in the hepatocytes. Apparently, these are sequelae of increased autophagia of lipids and increased lipid oxidation by the vinylchloride. In the sinusoids, activation, enlargement and proliferation of Kupffer cells was noted. The tendency of these cells to proliferate is apparently caused by the cancerogenic stimulation by vinylchloride. The prominent hyperplasia of lipocytes is probably connected with the deposition of collagen and the peculiar perisinusoidal fibrosis."}
{"id": "PMID:193246", "title": "[Iron containing nuclear inclusions in human pigmentary cirrhosis (author's transl)].", "content": "In human pigmentary cirrhosis nuclear (pseudo-)inclusions of cytoplasmic material, containing less or more degenerated and therefore faintly stained hemosiderin granules, are to be observed. But sometimes there are also finely fibrillar or granular proteinaceous materials, stainable by the Prussian-blue reaction, lying between the chromatin-strands or occupying the whole nucleus and displacing the chromatin to the nuclear envelope (margination of chromatin). Such uncoloured substances may condense into homogeneous masses and nearly hexagonal (0r related) crystals with a diameter up to 14 micron and a yellow-brownish colour, giving a strongly positive PERL's reaction. In contrast to the preceding stages intranuclear crystals of this kind have been observed in one case only. After destruction of the nuclear envelope and the marginated chromatin the crystals are lying free in the cytoplasm and later on, the cytoplasm being destroyed too, they may be ingested by von Kupffer cells. All the iron containing crystals, to be found in the cytoplasm, derive from former intranuclear inclusions. The intranuclear deposits of iron containing protein are interpreted as ferritin-aggregates. It is supposed that ferritin molecules, built up in the cytoplasm, do enter the nucleus via the pores of the nuclear envelope. Such an event not only signalizes a cytopathologic reaction but in turn may give rise to such additional cytopathologic lesions as cell shrinking and cell death.", "contents": "[Iron containing nuclear inclusions in human pigmentary cirrhosis (author's transl)]. In human pigmentary cirrhosis nuclear (pseudo-)inclusions of cytoplasmic material, containing less or more degenerated and therefore faintly stained hemosiderin granules, are to be observed. But sometimes there are also finely fibrillar or granular proteinaceous materials, stainable by the Prussian-blue reaction, lying between the chromatin-strands or occupying the whole nucleus and displacing the chromatin to the nuclear envelope (margination of chromatin). Such uncoloured substances may condense into homogeneous masses and nearly hexagonal (0r related) crystals with a diameter up to 14 micron and a yellow-brownish colour, giving a strongly positive PERL's reaction. In contrast to the preceding stages intranuclear crystals of this kind have been observed in one case only. After destruction of the nuclear envelope and the marginated chromatin the crystals are lying free in the cytoplasm and later on, the cytoplasm being destroyed too, they may be ingested by von Kupffer cells. All the iron containing crystals, to be found in the cytoplasm, derive from former intranuclear inclusions. The intranuclear deposits of iron containing protein are interpreted as ferritin-aggregates. It is supposed that ferritin molecules, built up in the cytoplasm, do enter the nucleus via the pores of the nuclear envelope. Such an event not only signalizes a cytopathologic reaction but in turn may give rise to such additional cytopathologic lesions as cell shrinking and cell death."}
{"id": "PMID:193245", "title": "The endocrine cells of the pancreas and related tumours. Ultrastructural study and classification.", "content": "Up to seven endocrine cell types have been identified ultrastructurally in the pancreas, including glucagon A cells, insulin B cells, somatostatin D cells, pancreatic peptide F cells and 5-hydroxytryptamine EC cells. In addition, D1 cells, which have been proposed as the cell type producing VIP and possible P cells of unknown function are seen. Various patterns of endocrine cell differentiation have been found in 20 endocrine pancreatic tumours. Well and poorly differentiated B cells have been identified in 6 insulinomas, diagnostic G cells in 3 out of 7 gastrinomas, D1 and/or F cells in 7 diarrheogenic tumours. Moreover, cells apparently unrelated to the prevalent clinical syndrome have been noted in 8 of the 20 tumours. Granular non diagnostic cells (poorly diagnostic gastrin cells? D1 cells?) were particularly frequent in gastrinomas; agranular or poorly granular cells, either by \"active\" or \"Stem cell\" type, were present in nearly all tumours, particularly in diarrheogenic tumours, gastrinomas and malignant insulinomas. A cytological classification of pancreatic endocrine tumours is proposed.", "contents": "The endocrine cells of the pancreas and related tumours. Ultrastructural study and classification. Up to seven endocrine cell types have been identified ultrastructurally in the pancreas, including glucagon A cells, insulin B cells, somatostatin D cells, pancreatic peptide F cells and 5-hydroxytryptamine EC cells. In addition, D1 cells, which have been proposed as the cell type producing VIP and possible P cells of unknown function are seen. Various patterns of endocrine cell differentiation have been found in 20 endocrine pancreatic tumours. Well and poorly differentiated B cells have been identified in 6 insulinomas, diagnostic G cells in 3 out of 7 gastrinomas, D1 and/or F cells in 7 diarrheogenic tumours. Moreover, cells apparently unrelated to the prevalent clinical syndrome have been noted in 8 of the 20 tumours. Granular non diagnostic cells (poorly diagnostic gastrin cells? D1 cells?) were particularly frequent in gastrinomas; agranular or poorly granular cells, either by \"active\" or \"Stem cell\" type, were present in nearly all tumours, particularly in diarrheogenic tumours, gastrinomas and malignant insulinomas. A cytological classification of pancreatic endocrine tumours is proposed."}
{"id": "PMID:193247", "title": "Effects of galactoflavin-induced riboflavin deficiency upon rat hepatic cell ultrastructure.", "content": "The primary cytoplasmic effect of galactoflavin-induced riboflavin deficiency upon rat liver cells involved focal sites of degradation which were manifested by the formation of membranous whorls. The nuclear effect of riboflavin deficiency concerned fluctuations in the total number of perichromatin granules per nucleus. These granules increased in number during the deficiency reaching a peak at three weeks. Nucleoli appeared compact with no evidence for segregation of nucleolar components. The possible correlation between increased synthesis of perichromatin granules and altered protein synthesis is discussed.", "contents": "Effects of galactoflavin-induced riboflavin deficiency upon rat hepatic cell ultrastructure. The primary cytoplasmic effect of galactoflavin-induced riboflavin deficiency upon rat liver cells involved focal sites of degradation which were manifested by the formation of membranous whorls. The nuclear effect of riboflavin deficiency concerned fluctuations in the total number of perichromatin granules per nucleus. These granules increased in number during the deficiency reaching a peak at three weeks. Nucleoli appeared compact with no evidence for segregation of nucleolar components. The possible correlation between increased synthesis of perichromatin granules and altered protein synthesis is discussed."}
{"id": "PMID:193254", "title": "Complementation between temperature-sensitive (ts) and host range nontransforming (hr-t) mutants of polyoma virus.", "content": "Two major classes of polyoma mutants are defective in cell transformation: early temperature-sensitive mutants of the tsA type which are defective in viral DNA synthesis and transformation at 39 degrees, but not at 32 degrees; and host range nontransforming (hr-t) mutants which fail to transform at either temperature. Mixed infection of mouse 3T3 cells by hr-t mutants and early tsA-type mutants results in enhanced growth of the tsA-type mutants at 39 degrees, indicating that the hr-t mutants can supply the early viral function required for viral DNA synthesis. The hr-t mutants also complement late is mutants which fail to produce infectious progeny at 39 degrees because of alterations in the 45,000-dalton major virion protein. Mixed infection of hamster BHK or rat Y1 cells by hr-t and tsA-type mutants results in efficient transformation at 39 degrees, indicating that the two classes of mutants can complement for transformation. No complementation is observed in pair-wise crosses among the early tsA-type mutants alone. The tsA-type mutants are located in the distal portion of the early region of the polyoma genome [Miller, L. K., and Fried, M. (1976) J. Virol. 18, 824-832]. The hr-t mutants are located in the proximal portion [Feunteun, J., Sompayrac, L., Fluck, M., and Benjamin, T. (1976) Proc. Nat. Acad. Sci. USA]. These results suggest that the early region of the polyoma genome is divided into two functional regions which can complement for transformation. The ts3 mutant of polyoma is located in the proximal portion of the late region.", "contents": "Complementation between temperature-sensitive (ts) and host range nontransforming (hr-t) mutants of polyoma virus. Two major classes of polyoma mutants are defective in cell transformation: early temperature-sensitive mutants of the tsA type which are defective in viral DNA synthesis and transformation at 39 degrees, but not at 32 degrees; and host range nontransforming (hr-t) mutants which fail to transform at either temperature. Mixed infection of mouse 3T3 cells by hr-t mutants and early tsA-type mutants results in enhanced growth of the tsA-type mutants at 39 degrees, indicating that the hr-t mutants can supply the early viral function required for viral DNA synthesis. The hr-t mutants also complement late is mutants which fail to produce infectious progeny at 39 degrees because of alterations in the 45,000-dalton major virion protein. Mixed infection of hamster BHK or rat Y1 cells by hr-t and tsA-type mutants results in efficient transformation at 39 degrees, indicating that the two classes of mutants can complement for transformation. No complementation is observed in pair-wise crosses among the early tsA-type mutants alone. The tsA-type mutants are located in the distal portion of the early region of the polyoma genome [Miller, L. K., and Fried, M. (1976) J. Virol. 18, 824-832]. The hr-t mutants are located in the proximal portion [Feunteun, J., Sompayrac, L., Fluck, M., and Benjamin, T. (1976) Proc. Nat. Acad. Sci. USA]. These results suggest that the early region of the polyoma genome is divided into two functional regions which can complement for transformation. The ts3 mutant of polyoma is located in the proximal portion of the late region."}
{"id": "PMID:193281", "title": "[Presence of iron in the composition of prolyl hydroxylase].", "content": "Binding of iron with the molecule of prolyl hydroxylase was studied using 59Fe. The label was administered into one-day-old rats and within 36 hours the enzyme was isolated from skin. After the final step of purification (DEAE cellulose) 59Fe was not found in fractions of prolyl hydroxylase. The purity of the enzyme preparations was controlled by polyacrylamide gel disc electrophoresis. The data obtained suggest that Fe ions are not inherent in the enzyme molecule.", "contents": "[Presence of iron in the composition of prolyl hydroxylase]. Binding of iron with the molecule of prolyl hydroxylase was studied using 59Fe. The label was administered into one-day-old rats and within 36 hours the enzyme was isolated from skin. After the final step of purification (DEAE cellulose) 59Fe was not found in fractions of prolyl hydroxylase. The purity of the enzyme preparations was controlled by polyacrylamide gel disc electrophoresis. The data obtained suggest that Fe ions are not inherent in the enzyme molecule."}
{"id": "PMID:193282", "title": "[Hypoxia and tissue permeability for non-electrolytes].", "content": "The activity of cytochrome oxidase in tissues was decreased in short-term adaptation to reduce pO2 and administration of KCN in small doses. In the former case the activities of peroxidase and catalase were increased in blood. These effects as well as administration of Na2ATP into rats led to an increase in water content in tissues, to soption of acidic vital stain (phenol red) and to decrease in the ether-soluble fraction of lipids. The alterations were accompanied by decreased permeability of cells to n-hexane (estimation by gas-liquid chromatography). The decrease in cell permeability for nonelectrolytes was apparently due to conformational alterations in protein molecule of cytoplasmic membranes.", "contents": "[Hypoxia and tissue permeability for non-electrolytes]. The activity of cytochrome oxidase in tissues was decreased in short-term adaptation to reduce pO2 and administration of KCN in small doses. In the former case the activities of peroxidase and catalase were increased in blood. These effects as well as administration of Na2ATP into rats led to an increase in water content in tissues, to soption of acidic vital stain (phenol red) and to decrease in the ether-soluble fraction of lipids. The alterations were accompanied by decreased permeability of cells to n-hexane (estimation by gas-liquid chromatography). The decrease in cell permeability for nonelectrolytes was apparently due to conformational alterations in protein molecule of cytoplasmic membranes."}
{"id": "PMID:193283", "title": "[Possible significance of hexokinase binding to mitochondrial membranes].", "content": "A magnitude of the Pasteur's effect and content of bound hexokinase were studied in various malignant and normal tissues. In all cases studied these two values were practically the same. Dynamics of changes in subcellular localization of hexokinase and the Pasteur's effect were similarly altered in liver tissue during ontogenesis. Binding hexokinase with mitochondrial membranes was assumed to be the cytophysiological mechanism for regulation of glycolytic activity by respiration.", "contents": "[Possible significance of hexokinase binding to mitochondrial membranes]. A magnitude of the Pasteur's effect and content of bound hexokinase were studied in various malignant and normal tissues. In all cases studied these two values were practically the same. Dynamics of changes in subcellular localization of hexokinase and the Pasteur's effect were similarly altered in liver tissue during ontogenesis. Binding hexokinase with mitochondrial membranes was assumed to be the cytophysiological mechanism for regulation of glycolytic activity by respiration."}
{"id": "PMID:193285", "title": "[Activity and stability of NAD.H-oxidase, succinate oxidase and cytochrome oxidase of rat liver and pancreatic mitochondria in chronic allergic colitis].", "content": "A comparative study of thermostability of NADH-, succinate- and cytochrome oxidases was carried out in liver mitochondria and pancreas of rats in normal state and in chronic allergic colitis. In the pathology degradative alterations occurred in mitochondria, which were manifested as a decrease in the stability of mitochondrial mutinzyme systems of tissues studies. The results suggested occurrence of latent impairments in structure of mitochondria.", "contents": "[Activity and stability of NAD.H-oxidase, succinate oxidase and cytochrome oxidase of rat liver and pancreatic mitochondria in chronic allergic colitis]. A comparative study of thermostability of NADH-, succinate- and cytochrome oxidases was carried out in liver mitochondria and pancreas of rats in normal state and in chronic allergic colitis. In the pathology degradative alterations occurred in mitochondria, which were manifested as a decrease in the stability of mitochondrial mutinzyme systems of tissues studies. The results suggested occurrence of latent impairments in structure of mitochondria."}
{"id": "PMID:193287", "title": "[Effect of carboxycathepsin on biological activity of bradykinin].", "content": "An effect of carboxycathepsin (peptidyl-dipeptidase EC 3.4.15.1) from bovine kidney on bradikinine was studied. The bradikinine activity was determined by monitoring the rat uterine horn retraction. Carboxycathepsin caused rapid inactivation of bradikinine (440-500 mcg of bradikinine/mg/min). The rate of bradikinine inactivation depended on the incubation time, content of the enzyme and substrate in the samples. In presence of EDTA carboxycathepsin did not inactivate bradikinine.", "contents": "[Effect of carboxycathepsin on biological activity of bradykinin]. An effect of carboxycathepsin (peptidyl-dipeptidase EC 3.4.15.1) from bovine kidney on bradikinine was studied. The bradikinine activity was determined by monitoring the rat uterine horn retraction. Carboxycathepsin caused rapid inactivation of bradikinine (440-500 mcg of bradikinine/mg/min). The rate of bradikinine inactivation depended on the incubation time, content of the enzyme and substrate in the samples. In presence of EDTA carboxycathepsin did not inactivate bradikinine."}
{"id": "PMID:193294", "title": "[Hexokinase activity in blood serum during carcinogenesis].", "content": "During carcinogenesis, induced by diethylnitrosamine in rats Wistar (in doses of 2.5 mg per Kg of weight daily with drinking water), the hexokinase (HK) activity in blood serum was observed with the appearance of the first morphological symptoms of tumor growth. It is observed mainly starting from the first months. At the end of the experimental period (8-9th month), when hepatomas develop in the liver, the HK activity in blood serum was noted almost in all cases. No serum HK activity was found in control rats.", "contents": "[Hexokinase activity in blood serum during carcinogenesis]. During carcinogenesis, induced by diethylnitrosamine in rats Wistar (in doses of 2.5 mg per Kg of weight daily with drinking water), the hexokinase (HK) activity in blood serum was observed with the appearance of the first morphological symptoms of tumor growth. It is observed mainly starting from the first months. At the end of the experimental period (8-9th month), when hepatomas develop in the liver, the HK activity in blood serum was noted almost in all cases. No serum HK activity was found in control rats."}
{"id": "PMID:193288", "title": "[Molecular aspects of the action of insulin].", "content": "Molecular aspects of the insulin action in an organism are discussed. The following mechanisms of the hormone effect are considered: induction of the synthesis of glycolytic enzymes in cell-targets under effect of insulin; mechanisms of the insulin reception in cell-enzymes in cell-targets; the possible role of cyclic nucleotides as mediators in the effect of insulin in cell targets.", "contents": "[Molecular aspects of the action of insulin]. Molecular aspects of the insulin action in an organism are discussed. The following mechanisms of the hormone effect are considered: induction of the synthesis of glycolytic enzymes in cell-targets under effect of insulin; mechanisms of the insulin reception in cell-enzymes in cell-targets; the possible role of cyclic nucleotides as mediators in the effect of insulin in cell targets."}
{"id": "PMID:193291", "title": "[Role of cyclic adenosine-3',5'-monophosphate in the regulation of histidase in the skin in the process of ontogeny].", "content": "In rat skin the histidase activity was observed 2--3 days before delivery; it was increased at the first days of postnatal development, achieving a maximal level at the 5th day and then it was decreased (within 2--3 weeks of postnatal development) to the level activity, which was found in adult animals. Concentration of urocaninic acid in skin correlated with the histidase activity. Content of urocaninic acid in skin and the histidase activity were altered under effect of administration of cylic-3',5'-AMP, dibutyryl cyclic-3',5'-AMP, glucagon, sodium fluoride, theophylline, actinomycin D and cycloheximide.", "contents": "[Role of cyclic adenosine-3',5'-monophosphate in the regulation of histidase in the skin in the process of ontogeny]. In rat skin the histidase activity was observed 2--3 days before delivery; it was increased at the first days of postnatal development, achieving a maximal level at the 5th day and then it was decreased (within 2--3 weeks of postnatal development) to the level activity, which was found in adult animals. Concentration of urocaninic acid in skin correlated with the histidase activity. Content of urocaninic acid in skin and the histidase activity were altered under effect of administration of cylic-3',5'-AMP, dibutyryl cyclic-3',5'-AMP, glucagon, sodium fluoride, theophylline, actinomycin D and cycloheximide."}
{"id": "PMID:193296", "title": "[Growth and the cellular transformation of undifferentiated nephroblastoma in tissue culture].", "content": "Cultivated undifferentiated malignant nephroblastoma would produce fibroblastoid zones of growth. The tumor cells differed from normal renal fibroblasts by an abundance of mitochondria; cell boundaries were not distinguished. No differentiations in tumor cells cultures absent in the primary material were noted.", "contents": "[Growth and the cellular transformation of undifferentiated nephroblastoma in tissue culture]. Cultivated undifferentiated malignant nephroblastoma would produce fibroblastoid zones of growth. The tumor cells differed from normal renal fibroblasts by an abundance of mitochondria; cell boundaries were not distinguished. No differentiations in tumor cells cultures absent in the primary material were noted."}
{"id": "PMID:193290", "title": "[Properties and action specificity of carboxycathepsin (peptidyl dipepsidase) from bovine kidneys].", "content": "Carboxycathepsin from bovine kidney split the dipeptide fragments from the C-terminal part of peptides of different structure. Peptides containing the proline residue at the second position from the C-terminal amino acid residue and also peptides with substituted terminal alpha-carboxyl group were not hydrolyzed by carboxycathepsin. The enzyme was activated by Cl, Zn2+, Co2+ and Mn2+. The substances which formed the chelate complexes with ions of two-valent metals and also heavy metal ions, inhibited the enzymatic activity. Diisopropyl fluorophosphate did not inhibit carboxycathepsin. The homogeneous preparation of carboxycathepsin converted angiotensin 1 into angiotensin 11 and hydrolyzed bradikinine, splitting off C-terminal dipeptides consequentially.", "contents": "[Properties and action specificity of carboxycathepsin (peptidyl dipepsidase) from bovine kidneys]. Carboxycathepsin from bovine kidney split the dipeptide fragments from the C-terminal part of peptides of different structure. Peptides containing the proline residue at the second position from the C-terminal amino acid residue and also peptides with substituted terminal alpha-carboxyl group were not hydrolyzed by carboxycathepsin. The enzyme was activated by Cl, Zn2+, Co2+ and Mn2+. The substances which formed the chelate complexes with ions of two-valent metals and also heavy metal ions, inhibited the enzymatic activity. Diisopropyl fluorophosphate did not inhibit carboxycathepsin. The homogeneous preparation of carboxycathepsin converted angiotensin 1 into angiotensin 11 and hydrolyzed bradikinine, splitting off C-terminal dipeptides consequentially."}
{"id": "PMID:193289", "title": "[Effect of amizil on phospholipid metabolism in different parts of the brain].", "content": "Effect of central M-cholinolytic amizyle on incorporation of 2-14C-acetate in phospholipids of big hemispheres, cortex of big hemispheres, cerebellum and stem was studied. In administration of amizyle the most distinct alterations were observed in cortex of big hemispheres and cerebellum. In cortex of big hemispheres the specific activity of inosine monophosphate and phosphatidyl choline were increased by 77% and 97%, respectively; the specific activity of phosphatidic acid was decreased by 63%. In cerebellum the specific activity of inosine monophosphate was decreased by 52.5% and of phosphatidyl serine was increased by 95%. Distinct alterations were not observed in the intensity of incorporation of labelled precursor into phospholipids of stem. In big hemispheres the specific activity of the only inosine monophosphate was decreased by 57%.", "contents": "[Effect of amizil on phospholipid metabolism in different parts of the brain]. Effect of central M-cholinolytic amizyle on incorporation of 2-14C-acetate in phospholipids of big hemispheres, cortex of big hemispheres, cerebellum and stem was studied. In administration of amizyle the most distinct alterations were observed in cortex of big hemispheres and cerebellum. In cortex of big hemispheres the specific activity of inosine monophosphate and phosphatidyl choline were increased by 77% and 97%, respectively; the specific activity of phosphatidic acid was decreased by 63%. In cerebellum the specific activity of inosine monophosphate was decreased by 52.5% and of phosphatidyl serine was increased by 95%. Distinct alterations were not observed in the intensity of incorporation of labelled precursor into phospholipids of stem. In big hemispheres the specific activity of the only inosine monophosphate was decreased by 57%."}
{"id": "PMID:193293", "title": "[Comparison of lipoprotein spectrum and lipids in maternal blood and in umbilical cord blood of newborn infant].", "content": "Content of beta- and pre-beta-lipoprotein fractions, total cholesterol and triglycerides was distinctly lower in blood serum of infant than in maternal one. In serum of funicular blood content of free fatty acids was 2.5-fold higher than in maternal blood serum; in erythrocytes of infant content of cholesterol was found to be higher by 40%, as compared with maternal erythrocytes. In blood serum of infant content of free cholesterol amounted to 28% of the total cholesterol at the same time in maternal blood it was equal to 37%. The highest proportion of cholesterol was found in alpha-lipoproteins of infant, in mother it was observed in beta-lipoproteins. In blood of infant and mother the same types of lipoproteins were present but their quantitative ratio was different. The main lipoproteins of infant were shown to be alpha-lipoproteins. Relationship between the content of cholesterol in pre-beta-lipoproteins (correlation coefficient 0.64) was noted in blood of mother and infant.", "contents": "[Comparison of lipoprotein spectrum and lipids in maternal blood and in umbilical cord blood of newborn infant]. Content of beta- and pre-beta-lipoprotein fractions, total cholesterol and triglycerides was distinctly lower in blood serum of infant than in maternal one. In serum of funicular blood content of free fatty acids was 2.5-fold higher than in maternal blood serum; in erythrocytes of infant content of cholesterol was found to be higher by 40%, as compared with maternal erythrocytes. In blood serum of infant content of free cholesterol amounted to 28% of the total cholesterol at the same time in maternal blood it was equal to 37%. The highest proportion of cholesterol was found in alpha-lipoproteins of infant, in mother it was observed in beta-lipoproteins. In blood of infant and mother the same types of lipoproteins were present but their quantitative ratio was different. The main lipoproteins of infant were shown to be alpha-lipoproteins. Relationship between the content of cholesterol in pre-beta-lipoproteins (correlation coefficient 0.64) was noted in blood of mother and infant."}
{"id": "PMID:193297", "title": "[Nutrition and state of health of older persons during physiologic aging].", "content": "Features peculiar to actual nutritional pattern (in family) of persons of advanced and old age in physiological ageing were studied. According to a fairly broad range of characteristics (cardio-vascular function, blood coagulation system, lipids metabolism parameters, body weight, general clinical diagnosis, etc.) their health status was determined. The alimentation of the examined is shown to be characterized by marked individual peculiarities. On the whole it conforms to the existing recommendations, although there is noted a certain deficiency of proteins, vitamins and mineral elements. Differences in the nutrition of males and females were established. The calorific value of the nutrition declines parallel with the increasing age. Its comparison with the health characteristics of the examined testifies to the presence of a close relationship between them. More favourable indices of the bioelectric activity of the heart, myocardial contractility, the trends in the lipids metabolism, body weight, the blood clotting activity were registered in persons with reduced calorific value of the alimentation.", "contents": "[Nutrition and state of health of older persons during physiologic aging]. Features peculiar to actual nutritional pattern (in family) of persons of advanced and old age in physiological ageing were studied. According to a fairly broad range of characteristics (cardio-vascular function, blood coagulation system, lipids metabolism parameters, body weight, general clinical diagnosis, etc.) their health status was determined. The alimentation of the examined is shown to be characterized by marked individual peculiarities. On the whole it conforms to the existing recommendations, although there is noted a certain deficiency of proteins, vitamins and mineral elements. Differences in the nutrition of males and females were established. The calorific value of the nutrition declines parallel with the increasing age. Its comparison with the health characteristics of the examined testifies to the presence of a close relationship between them. More favourable indices of the bioelectric activity of the heart, myocardial contractility, the trends in the lipids metabolism, body weight, the blood clotting activity were registered in persons with reduced calorific value of the alimentation."}
{"id": "PMID:193292", "title": "[HCO3- -stimulated ATPase of rat kidneys].", "content": "In homogenate and mitochondria of cortex and medulla of rat kidney a stimulating effect of different concentrations of bicarbonate on the ATPase activity was studied. By the rate of inhibition of Mg2+-ATPase and HCO3-ATPase, thiocyanate, perchlorate and azide were distributed as follows: N3 greater than CNS greater than ClO4. Thiocyanate inhibited non-competitively the HCO3-stimulated ATPase activity. The similarity was observed between HCO3-stimulated ATPase from rat kidney and bicarbonate-stimulated ATPase from other cells.", "contents": "[HCO3- -stimulated ATPase of rat kidneys]. In homogenate and mitochondria of cortex and medulla of rat kidney a stimulating effect of different concentrations of bicarbonate on the ATPase activity was studied. By the rate of inhibition of Mg2+-ATPase and HCO3-ATPase, thiocyanate, perchlorate and azide were distributed as follows: N3 greater than CNS greater than ClO4. Thiocyanate inhibited non-competitively the HCO3-stimulated ATPase activity. The similarity was observed between HCO3-stimulated ATPase from rat kidney and bicarbonate-stimulated ATPase from other cells."}
{"id": "PMID:193305", "title": "[New concepts on central regulation of the blood pressure. Mode of action of clonidine and alpha-methyl DOPA (author's transl)].", "content": "A review is presented of several reports which strongly indicate that the reaction pattern of \"cardiovascular depression\" (decrease in blood pressure, heart rate and cardiac output) is triggered off by the stimulation of alpha-adrenoceptors in the brain. The efferent information is mediated by an inhibition of the sympathetic and by an activation of the cardiac vagal system. The central alpha-adrenoceptors, which are localized within the medulla, are stimulated by the antihypertensive agents clonidine and alpha-methyl-DOPA, and also by central administration of other sympathomimetic drugs such as naphazoline, oxymetazoline, amphetamine and others. It can be assumed  that these drugs mimic the action of endogenous nor-adrenaline, which is present in considerable amounts in the brain stem, and which might, under physiological conditions, mediate the pattern of cardiovascular depression.", "contents": "[New concepts on central regulation of the blood pressure. Mode of action of clonidine and alpha-methyl DOPA (author's transl)]. A review is presented of several reports which strongly indicate that the reaction pattern of \"cardiovascular depression\" (decrease in blood pressure, heart rate and cardiac output) is triggered off by the stimulation of alpha-adrenoceptors in the brain. The efferent information is mediated by an inhibition of the sympathetic and by an activation of the cardiac vagal system. The central alpha-adrenoceptors, which are localized within the medulla, are stimulated by the antihypertensive agents clonidine and alpha-methyl-DOPA, and also by central administration of other sympathomimetic drugs such as naphazoline, oxymetazoline, amphetamine and others. It can be assumed  that these drugs mimic the action of endogenous nor-adrenaline, which is present in considerable amounts in the brain stem, and which might, under physiological conditions, mediate the pattern of cardiovascular depression."}
{"id": "PMID:193302", "title": "[Mutual stimulation of oncornavirus and herpetic infections in experiments in vivo and in vitro].", "content": "The evidence of mutual stimulation of herpes simplex virus (HSV) and oncornaviruses (OV) reproduction was obtained. HSV titers in mice pre-infected with Rauscher leukosis virus (RLV) were 2.25-3.0 lg LD50 higher than in mice of the same batch but without RLV infection. The continuous HEp-2 culture chronically infected with oncornaviruses was found to be more sensitive to the cytopathic effect of HSV strains, types 1 and 2, and in the culture fluid HSV accumulated to a greater titer than in primarily trypsinized culture of chick embryo fibroblasts. Electron microscope examinations of the continuous J-96 cell culture chronically infected with OV and HSV simultaneously revealed an 8.3-fold increase in the number of oncornavirus particles as compared to the control culture, infected with OV alone.", "contents": "[Mutual stimulation of oncornavirus and herpetic infections in experiments in vivo and in vitro]. The evidence of mutual stimulation of herpes simplex virus (HSV) and oncornaviruses (OV) reproduction was obtained. HSV titers in mice pre-infected with Rauscher leukosis virus (RLV) were 2.25-3.0 lg LD50 higher than in mice of the same batch but without RLV infection. The continuous HEp-2 culture chronically infected with oncornaviruses was found to be more sensitive to the cytopathic effect of HSV strains, types 1 and 2, and in the culture fluid HSV accumulated to a greater titer than in primarily trypsinized culture of chick embryo fibroblasts. Electron microscope examinations of the continuous J-96 cell culture chronically infected with OV and HSV simultaneously revealed an 8.3-fold increase in the number of oncornavirus particles as compared to the control culture, infected with OV alone."}
{"id": "PMID:193299", "title": "[Effect of a new food product--cryl paste--on chemical carcinogenesis].", "content": "The influence of a new food product obtained from oceanic shrimp--the cryl on the development of tumours under the effect of chemical carcinogens was investigated. DAB (n-dimethylaminobenzene) induced tumours of the liver in 90.8% of the test rats against the background of a caseine-rich diet and in 21.7% of the animals receiving the cryl paste as a part of their alimentation. With the diethylnitrosamine (DENA) induced tumours the lowest percentage (43) and inhibited development were noted with the rats fed on the cryl paste, and the highest--when feeding the animals of beef (74), whereas in the case of a caseine-rich diet--tumours developed in 50% of the animals. Features specific for morphogenesis of tumours induced with DENA with the animals kept on a diet containing different types of protein and also histo- and biochemical changes in the liver in carcinogenesis were studied.", "contents": "[Effect of a new food product--cryl paste--on chemical carcinogenesis]. The influence of a new food product obtained from oceanic shrimp--the cryl on the development of tumours under the effect of chemical carcinogens was investigated. DAB (n-dimethylaminobenzene) induced tumours of the liver in 90.8% of the test rats against the background of a caseine-rich diet and in 21.7% of the animals receiving the cryl paste as a part of their alimentation. With the diethylnitrosamine (DENA) induced tumours the lowest percentage (43) and inhibited development were noted with the rats fed on the cryl paste, and the highest--when feeding the animals of beef (74), whereas in the case of a caseine-rich diet--tumours developed in 50% of the animals. Features specific for morphogenesis of tumours induced with DENA with the animals kept on a diet containing different types of protein and also histo- and biochemical changes in the liver in carcinogenesis were studied."}
{"id": "PMID:193308", "title": "[Effect of Cu++ ions on the morphological, cytological, and physiological state of Candida utilis cells in continuous culture].", "content": "Cells of Candida utilis grown in continuous culture under the influence of rather high concentrations of copper ions have been studied biochemically, morphologically, and cytologically. Although under these conditions a new steady state has been adjusted, the population is much more differentiated than under control conditions. With regard to their size, structure, and viability the cells have been arranged into 4 groups. Generally, the \"copper cells\" in comparison with the \"normal cells\" are more voluminous (average: 2.5 times; maximum: 4 times) and of altered structure. The appearance of dense particles (\"copper containing particles\"), globules (\"lipid globules\"), vacuoles, and the thickening of the cell wall, as well as the disappearance of the mitochondrial cristae have been shown as characteristic indications for damage in the cell substructure caused by the influence of copper ions. Occasionally abnormal cell shapes can be observed. A permanent influence of copper ions in the concentration used was followed also by striking disturbances of the cell metabolism. The cells take up more carbon, phosphorus, and nitrogen, whereas protein synthesis and respiratory activity decrease. Both the synthesis of lipids and polysaccharides and the phosphohydrolase activity increase. A discussion of the experimental data is presented.", "contents": "[Effect of Cu++ ions on the morphological, cytological, and physiological state of Candida utilis cells in continuous culture]. Cells of Candida utilis grown in continuous culture under the influence of rather high concentrations of copper ions have been studied biochemically, morphologically, and cytologically. Although under these conditions a new steady state has been adjusted, the population is much more differentiated than under control conditions. With regard to their size, structure, and viability the cells have been arranged into 4 groups. Generally, the \"copper cells\" in comparison with the \"normal cells\" are more voluminous (average: 2.5 times; maximum: 4 times) and of altered structure. The appearance of dense particles (\"copper containing particles\"), globules (\"lipid globules\"), vacuoles, and the thickening of the cell wall, as well as the disappearance of the mitochondrial cristae have been shown as characteristic indications for damage in the cell substructure caused by the influence of copper ions. Occasionally abnormal cell shapes can be observed. A permanent influence of copper ions in the concentration used was followed also by striking disturbances of the cell metabolism. The cells take up more carbon, phosphorus, and nitrogen, whereas protein synthesis and respiratory activity decrease. Both the synthesis of lipids and polysaccharides and the phosphohydrolase activity increase. A discussion of the experimental data is presented."}
{"id": "PMID:193309", "title": "Antiviral activity of certain hetarylhydrazones in Mengo virus infected mice.", "content": "Out of a series of eleven related hetarylhydrazones four derivatives (ZIMET 124/73, ZIMET 38/74, ZIMET 44/69, and IMET 98/69), after subcutaneous administration (0.5 mmole/kg per injection), were found to possess significant antiviral activity against rapidly progressing and highly lethal Mengo virus encephalitis in mice. After peroral administration (2 mmole/kg per injection) only with IMET 98/69 significant protection was achieved. Drug treatments were given twice daily for 5 days. The effectiveness of compounds was evidenced by significant \"rates of protection\". Possible relationships between the antiviral activity and the structure of compounds are discussed.", "contents": "Antiviral activity of certain hetarylhydrazones in Mengo virus infected mice. Out of a series of eleven related hetarylhydrazones four derivatives (ZIMET 124/73, ZIMET 38/74, ZIMET 44/69, and IMET 98/69), after subcutaneous administration (0.5 mmole/kg per injection), were found to possess significant antiviral activity against rapidly progressing and highly lethal Mengo virus encephalitis in mice. After peroral administration (2 mmole/kg per injection) only with IMET 98/69 significant protection was achieved. Drug treatments were given twice daily for 5 days. The effectiveness of compounds was evidenced by significant \"rates of protection\". Possible relationships between the antiviral activity and the structure of compounds are discussed."}
{"id": "PMID:193303", "title": "[Antibodies to Epstein-Barr virus in the sera of children with different neoplasms].", "content": "The presence of antibody to virus capsid antigen (VCA) of Epstein-Barr virus (EBV) was determined in sera from children with various forms of neoplasia by the indirect immunofluorescence procedure of Henle. Eighty-one sera from children with Wilms tumor, teratoblastoma, reticulosarcoma, neuroblastoma, soft tissue sarcoma, as well as from children with benign tumors were examined. The controls included sera from normal children of the same ages. The test cells synthesizing VCA were suspension cultures of P3HR-1 cells which are one of the clones of Burkitt lymphoma. The studies showed no increase in the content of antibody to EBV in any of the groups of children with tumors as compared with the controls. It was also found that the percentage of EBV infection in various groups of sick and normal children varied from 82 to 100.", "contents": "[Antibodies to Epstein-Barr virus in the sera of children with different neoplasms]. The presence of antibody to virus capsid antigen (VCA) of Epstein-Barr virus (EBV) was determined in sera from children with various forms of neoplasia by the indirect immunofluorescence procedure of Henle. Eighty-one sera from children with Wilms tumor, teratoblastoma, reticulosarcoma, neuroblastoma, soft tissue sarcoma, as well as from children with benign tumors were examined. The controls included sera from normal children of the same ages. The test cells synthesizing VCA were suspension cultures of P3HR-1 cells which are one of the clones of Burkitt lymphoma. The studies showed no increase in the content of antibody to EBV in any of the groups of children with tumors as compared with the controls. It was also found that the percentage of EBV infection in various groups of sick and normal children varied from 82 to 100."}
{"id": "PMID:193311", "title": "[Oncogeny of herpes simplex viruses and lupidon].", "content": "The part of the herpes simplex virus type 2 in the development of the cervex carcinoma of women is still an open question. After the serological findings that patients with cervix carcinoma have a higher rate of antibodies against type 2 than healthy women, which were initially published with great expectation, the molecular-virological examinations which were meanwhile carried out by several work groups to find traces of the herpes simplex virus type 2 in the carcinoma cells were negative, except some few but not confirmed cases. Hitherto but the results of transformation of embryonic hamster cells by UV-inactivated virus were the strongest indication for the herpes simplex virus possibly having oncogenic power, although one of the most important demonstrations, i.e. that of the virus DNA, is still lacking even for these transformed cells, which induce fibrosarcoma if injected to newborn hamsters. Possibly the transformation of the normal hamster cell into a tumor cell requires but such a small quantity of the herpes simplex virus DNA that it cannot be traced with the present methods. In connection with the question of the herpes simplex virus being oncogenic also LUPIDON which contains heat-inactivated herpes simplex virus, was examined. For this purpose extended transformation experiments in vitro and animal experiments with new-born hamsters were carried out. All these experiments had a negative result. There is thus no indication for LUPIDON having oncogenic properties.", "contents": "[Oncogeny of herpes simplex viruses and lupidon]. The part of the herpes simplex virus type 2 in the development of the cervex carcinoma of women is still an open question. After the serological findings that patients with cervix carcinoma have a higher rate of antibodies against type 2 than healthy women, which were initially published with great expectation, the molecular-virological examinations which were meanwhile carried out by several work groups to find traces of the herpes simplex virus type 2 in the carcinoma cells were negative, except some few but not confirmed cases. Hitherto but the results of transformation of embryonic hamster cells by UV-inactivated virus were the strongest indication for the herpes simplex virus possibly having oncogenic power, although one of the most important demonstrations, i.e. that of the virus DNA, is still lacking even for these transformed cells, which induce fibrosarcoma if injected to newborn hamsters. Possibly the transformation of the normal hamster cell into a tumor cell requires but such a small quantity of the herpes simplex virus DNA that it cannot be traced with the present methods. In connection with the question of the herpes simplex virus being oncogenic also LUPIDON which contains heat-inactivated herpes simplex virus, was examined. For this purpose extended transformation experiments in vitro and animal experiments with new-born hamsters were carried out. All these experiments had a negative result. There is thus no indication for LUPIDON having oncogenic properties."}
{"id": "PMID:193312", "title": "[Epidemiology of herpes simplex diseases].", "content": "The epidemiological principle of the herpes simplex virus (HSV) infections is to have the affected host survive, to persist in it and thus to make it to be a life long starting point for new infection chains. There is an accurately tuned correlation between virus and host organism, in which the persistence of the virus as a latent infection in the ganglion cells of sensory neurones is of central importance. In this state the virus cannot be attacked by the defensive power of the body. When changing from latency in the ganglion cell to activity in the periphery it utilizes the nerve conduction. It has not yet been cleared which factors are responsible for the change-over from the productive, cytocide infection to the latent infection, how the latency is being stabilized and how the reactivation to the herpes recidivans takes place. The organ and tissue specifity of both the HSV types 1 and 2 seems to be bound to the entire pathogenetic complex so that inspite of occasional reverse infections HSV type 1 remains epidemiologically the facial virus type and HSV type 2 the genital one. Apparent and inapparent rimary infections and relapes lead to numerous uncontrolled contacts so that the rate of infection is 50% until the age of puberty and 80% in middle-age adults. The contamination with the mainly venerically transmitted HSV type 2 starts with the age of puberty and reaches abt. 10 to 15% of our population. In patients suffering from cervix carcinoma antibodies against herpes simplex virus type 2 are more frequently demonstrated. Comparative examinations have shown that an increased exposition cannot be the sole cause for this prevalence. The kind of relationship between herpes genitalis and cervix carcinoma remains, however, unclear.", "contents": "[Epidemiology of herpes simplex diseases]. The epidemiological principle of the herpes simplex virus (HSV) infections is to have the affected host survive, to persist in it and thus to make it to be a life long starting point for new infection chains. There is an accurately tuned correlation between virus and host organism, in which the persistence of the virus as a latent infection in the ganglion cells of sensory neurones is of central importance. In this state the virus cannot be attacked by the defensive power of the body. When changing from latency in the ganglion cell to activity in the periphery it utilizes the nerve conduction. It has not yet been cleared which factors are responsible for the change-over from the productive, cytocide infection to the latent infection, how the latency is being stabilized and how the reactivation to the herpes recidivans takes place. The organ and tissue specifity of both the HSV types 1 and 2 seems to be bound to the entire pathogenetic complex so that inspite of occasional reverse infections HSV type 1 remains epidemiologically the facial virus type and HSV type 2 the genital one. Apparent and inapparent rimary infections and relapes lead to numerous uncontrolled contacts so that the rate of infection is 50% until the age of puberty and 80% in middle-age adults. The contamination with the mainly venerically transmitted HSV type 2 starts with the age of puberty and reaches abt. 10 to 15% of our population. In patients suffering from cervix carcinoma antibodies against herpes simplex virus type 2 are more frequently demonstrated. Comparative examinations have shown that an increased exposition cannot be the sole cause for this prevalence. The kind of relationship between herpes genitalis and cervix carcinoma remains, however, unclear."}
{"id": "PMID:193313", "title": "[Histochemistry of the carbohydrate metabolism in cysts of Toxoplasma gondii (author's transl)].", "content": "Mice were infected with cysts of the ALT strain Toxoplasma by intraperitoneal injection. After 2-8 weeks disseminated cysts could be demonstrated in the brain tissue. All cysts showed identical histochemical characteristics, independent of their sizes or their cell number. The encysted organisms were intensely stained after the PAS-reaction. This polysaccharide is highly diastase and acid resistant. Glycogen synthetase activity could not be demonstrated, but phosphorylase activity was very high. The energy metabolism was characterized by a high lactate dehydrogenase activity, whereas the reaction for succinate dehydrogenase activity only leads to sparse deposits of reaction products. The carbohydrate content is interpreted to be not only a store of energy substrate but also a store of biosynthetic substrate. It is assumed that a part of the liberated glucose at high activities of G-6-P-DH and 6-P-G-DH is metabolized by the hexose monophosphate shunt, the pentoses of which may contribute to nucleic acid synthesis which is necessary for the proliferation of the encysted organisms.", "contents": "[Histochemistry of the carbohydrate metabolism in cysts of Toxoplasma gondii (author's transl)]. Mice were infected with cysts of the ALT strain Toxoplasma by intraperitoneal injection. After 2-8 weeks disseminated cysts could be demonstrated in the brain tissue. All cysts showed identical histochemical characteristics, independent of their sizes or their cell number. The encysted organisms were intensely stained after the PAS-reaction. This polysaccharide is highly diastase and acid resistant. Glycogen synthetase activity could not be demonstrated, but phosphorylase activity was very high. The energy metabolism was characterized by a high lactate dehydrogenase activity, whereas the reaction for succinate dehydrogenase activity only leads to sparse deposits of reaction products. The carbohydrate content is interpreted to be not only a store of energy substrate but also a store of biosynthetic substrate. It is assumed that a part of the liberated glucose at high activities of G-6-P-DH and 6-P-G-DH is metabolized by the hexose monophosphate shunt, the pentoses of which may contribute to nucleic acid synthesis which is necessary for the proliferation of the encysted organisms."}
{"id": "PMID:193314", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. III. Occurence of diphosphatases in muscular tissue (authors' transl)].", "content": "After a review on the present knowledge of the occurence of diphosphatases in muscular tissue own data of the diphosphatase acitivity in the bovine longissimus muscle of nine animals are reported. Remarkable differences between animals were observed, the diphosphatase activity being much lower than the tripolyphosphatase activity.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. III. Occurence of diphosphatases in muscular tissue (authors' transl)]. After a review on the present knowledge of the occurence of diphosphatases in muscular tissue own data of the diphosphatase acitivity in the bovine longissimus muscle of nine animals are reported. Remarkable differences between animals were observed, the diphosphatase activity being much lower than the tripolyphosphatase activity."}
{"id": "PMID:193315", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. IV. Change in the tripolyphosphatase activity of muscle post mortem (author's transl)].", "content": "The triphosphatase (TPase) activity of minced bovine muscle increased during storage of the intact muscle post mortem; after development of rigor mortis it remained constant. The TPase activity of porcine muscle is influenced by the rate ofpost mortem glycolysis.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. IV. Change in the tripolyphosphatase activity of muscle post mortem (author's transl)]. The triphosphatase (TPase) activity of minced bovine muscle increased during storage of the intact muscle post mortem; after development of rigor mortis it remained constant. The TPase activity of porcine muscle is influenced by the rate ofpost mortem glycolysis."}
{"id": "PMID:193316", "title": "Production of aflatoxin B1 and G1 by Aspergillus parasiticus on silica gels.", "content": "Silica gels were prepared by acidifying alkaline silicate solutions with phosphoric or tartaric acid. Various combinations of glucose, sucrose, yeast extract, and salts were included in the gels an nutrients. Maximum production of aflatoxins B1 and G1 occurred when silica gel (0.4 to 0.5 cm deep in a petri dish) containing 20% sucrose and 2% yeast extract, and gelled with tartaric acid, was inoculated with approximately 120 to 12000 spores of Aspergillus parasiticus per plate; and plates were incubated at 28 degrees C for 10 days.", "contents": "Production of aflatoxin B1 and G1 by Aspergillus parasiticus on silica gels. Silica gels were prepared by acidifying alkaline silicate solutions with phosphoric or tartaric acid. Various combinations of glucose, sucrose, yeast extract, and salts were included in the gels an nutrients. Maximum production of aflatoxins B1 and G1 occurred when silica gel (0.4 to 0.5 cm deep in a petri dish) containing 20% sucrose and 2% yeast extract, and gelled with tartaric acid, was inoculated with approximately 120 to 12000 spores of Aspergillus parasiticus per plate; and plates were incubated at 28 degrees C for 10 days."}
{"id": "PMID:193317", "title": "[Genetical investigation of adenylate kinase in the population of the L\u00fcbeck area using agarose-thin-layer electrophoresis (author's transl)].", "content": "Adenylate kinase phenotypes were determined in a sample of 604 persons in the vicinity of L\u00fcbeck by means of thin-layer agarose-electrophoresis: A gene frequency of 0,9577 was estimated for AK1 and 0.0423 for AK2.", "contents": "[Genetical investigation of adenylate kinase in the population of the L\u00fcbeck area using agarose-thin-layer electrophoresis (author's transl)]. Adenylate kinase phenotypes were determined in a sample of 604 persons in the vicinity of L\u00fcbeck by means of thin-layer agarose-electrophoresis: A gene frequency of 0,9577 was estimated for AK1 and 0.0423 for AK2."}
{"id": "PMID:193324", "title": "[Use of the passive hemagglutination test for the purpose of determining antibody levels following animal immunization with Cl. perfringens toxoid].", "content": "Data are presented on the study of possibilities of the application of the passive hemagglutination test for titration of the blood sera of mice, guinea pigs and rabbits immunized with Cl. perfringens toxoid. A diagnostic agent obtained by the sensitization of formalin- and tannin-treated sheep erythrocytes with the serologically pure toxoid, and homologous sera (as standard) were used in this test. A high immune response of BALB/c and C3H mice to the Cl. perfringens toxoid permits to suggest inbred mice as a model for the immunological and immunogenetic studies connected with this toxoid.", "contents": "[Use of the passive hemagglutination test for the purpose of determining antibody levels following animal immunization with Cl. perfringens toxoid]. Data are presented on the study of possibilities of the application of the passive hemagglutination test for titration of the blood sera of mice, guinea pigs and rabbits immunized with Cl. perfringens toxoid. A diagnostic agent obtained by the sensitization of formalin- and tannin-treated sheep erythrocytes with the serologically pure toxoid, and homologous sera (as standard) were used in this test. A high immune response of BALB/c and C3H mice to the Cl. perfringens toxoid permits to suggest inbred mice as a model for the immunological and immunogenetic studies connected with this toxoid."}
{"id": "PMID:193325", "title": "[Epidemiologic features of acute viral respiratory infections in familial foci].", "content": "A study was made of the epidemiological peculiarities of viral respiratory infections of various etiology in the familial foci with the use of a methodical approach permitting to detect the true spread of infection in the familial foci, with consideration to the subclinical forme fruste of the disease and \"carrier state\". It appeared that in the familial foci the infectiousness of the majority of respiratory viral infections was greater than in the closed collective bodies uniting persons of the same age. The age composition of the family influences the manifestness (particularly in parainfluenza infection) and the intensity of the epidemic process characterized by the coefficient of the secondary affections. The type of the apartment, the floor on which it is located, and the number of persons residing in it had no significant influence on the spread of the viral infections in the familial foci. A definite role in this process is played by the level of specific serum antibodies in the members of the family surrounding the patient. The association of morbidity level with the antibody level proved to be the most distinct in children with influenza and adenoviral infection; this association was less significant in adults.", "contents": "[Epidemiologic features of acute viral respiratory infections in familial foci]. A study was made of the epidemiological peculiarities of viral respiratory infections of various etiology in the familial foci with the use of a methodical approach permitting to detect the true spread of infection in the familial foci, with consideration to the subclinical forme fruste of the disease and \"carrier state\". It appeared that in the familial foci the infectiousness of the majority of respiratory viral infections was greater than in the closed collective bodies uniting persons of the same age. The age composition of the family influences the manifestness (particularly in parainfluenza infection) and the intensity of the epidemic process characterized by the coefficient of the secondary affections. The type of the apartment, the floor on which it is located, and the number of persons residing in it had no significant influence on the spread of the viral infections in the familial foci. A definite role in this process is played by the level of specific serum antibodies in the members of the family surrounding the patient. The association of morbidity level with the antibody level proved to be the most distinct in children with influenza and adenoviral infection; this association was less significant in adults."}
{"id": "PMID:193328", "title": "Proteolytic activity of subcellular fractions from Streptomyces griseus no. 45-H.", "content": "Subcellular fractions were prepared from Streptomyces griseus No. 45-H at different stages of life cycle, and their proteolytic activity was examined. The highest proteolytic activity was found in the 24- and 72- h-old vegetative hyphae, the lowest in the resting spores. Spores contained about 9--30% of the proteolytic activity of vegetative cells. At the age of 16 h about 80%, at 26 h 70%, at 72 h 40%, and in spores about 60% of the proteolytic activity was particulate. The greatest part of the proteolytic activity could be inhibited by EDTA, lower levels of serine and sulfhydryl protease activities were detected in the cell-free extracts of vegetative cells.", "contents": "Proteolytic activity of subcellular fractions from Streptomyces griseus no. 45-H. Subcellular fractions were prepared from Streptomyces griseus No. 45-H at different stages of life cycle, and their proteolytic activity was examined. The highest proteolytic activity was found in the 24- and 72- h-old vegetative hyphae, the lowest in the resting spores. Spores contained about 9--30% of the proteolytic activity of vegetative cells. At the age of 16 h about 80%, at 26 h 70%, at 72 h 40%, and in spores about 60% of the proteolytic activity was particulate. The greatest part of the proteolytic activity could be inhibited by EDTA, lower levels of serine and sulfhydryl protease activities were detected in the cell-free extracts of vegetative cells."}
{"id": "PMID:193330", "title": "Cyclic AMP and metabolic substrates in hemorrhagic shock of the rat.", "content": "Hemorrhagic shock was induced in rats by bleeding to 35 mmHg for a period of 4 h. Plasma glucose increased rapidly following the onset of bleeding and reached twice the control value after 30 min. After 2 h hypotension the liver content of glycogen was depleted and subsequently the rats became hypoglycemic. The rise in plasma glucose was accompanied by a rise in plasma cyclic AMP, which was 10-fold after 1 h, but returned towards control values at the end of the hypotensive period. There were no corresponding changes in the cyclic AMP contents of liver, heart or adipose tissue. Blood lactate was increased 10-fold and the lactate/pyruvate ratio was more than doubled, suggesting an increased anaerobic metabolism. Plasma FFA levels fell significantly, while plasma glycerol was unchanged during the hypotensive period. In this hemorrhagic shock model there is an initial phase of glucose mobilization from the liver, which is accompanied by elevated plasma cyclic AMP. This phase is followed by a period of depressed levels of glucose as well as FFA and thus a lack of metabolizable substrates in plasma.", "contents": "Cyclic AMP and metabolic substrates in hemorrhagic shock of the rat. Hemorrhagic shock was induced in rats by bleeding to 35 mmHg for a period of 4 h. Plasma glucose increased rapidly following the onset of bleeding and reached twice the control value after 30 min. After 2 h hypotension the liver content of glycogen was depleted and subsequently the rats became hypoglycemic. The rise in plasma glucose was accompanied by a rise in plasma cyclic AMP, which was 10-fold after 1 h, but returned towards control values at the end of the hypotensive period. There were no corresponding changes in the cyclic AMP contents of liver, heart or adipose tissue. Blood lactate was increased 10-fold and the lactate/pyruvate ratio was more than doubled, suggesting an increased anaerobic metabolism. Plasma FFA levels fell significantly, while plasma glycerol was unchanged during the hypotensive period. In this hemorrhagic shock model there is an initial phase of glucose mobilization from the liver, which is accompanied by elevated plasma cyclic AMP. This phase is followed by a period of depressed levels of glucose as well as FFA and thus a lack of metabolizable substrates in plasma."}
{"id": "PMID:193327", "title": "[Functional state of the adrenal cortex in patients with Parkinsonism before and after surgical treatment].", "content": "The results of biochemical examinations of the hormonal function of the adrenal cortex in 22 patients with Parkinson's disease are presented as seen prior and following stereotaxic operations on the ventro-lateral nucleus of the thalamus. It was found that parkinsonics have a decreased androgenic, glucocorticoid and mineralocorticoid function of the adrenal cortex. Long history and growing severity of the disease manifest themselves in a distinct inhibition of the adrenal cortex function. The importance of the changes in the functional state of the hypothalamo-hypophyseal system in the revealed disorders in the hormonal activity is emphasized. Along with a beneficial clinical effect surgery brings about an improvement of the functional state of the adrenal cortex.", "contents": "[Functional state of the adrenal cortex in patients with Parkinsonism before and after surgical treatment]. The results of biochemical examinations of the hormonal function of the adrenal cortex in 22 patients with Parkinson's disease are presented as seen prior and following stereotaxic operations on the ventro-lateral nucleus of the thalamus. It was found that parkinsonics have a decreased androgenic, glucocorticoid and mineralocorticoid function of the adrenal cortex. Long history and growing severity of the disease manifest themselves in a distinct inhibition of the adrenal cortex function. The importance of the changes in the functional state of the hypothalamo-hypophyseal system in the revealed disorders in the hormonal activity is emphasized. Along with a beneficial clinical effect surgery brings about an improvement of the functional state of the adrenal cortex."}
{"id": "PMID:193335", "title": "Urinary aldosterone excretion rate and plasma aldosterone concentration in the rat: effect of ACTH, DOC, furosemide and of changes in sodium balance.", "content": "In rats kept under standard conditions urinary aldosterone exretion rate (UAER) and plasma aldosterone concentration (PAC) showed a circadian rhythm with peak values at the beginning of the dark perioith a single dose of DOC (2 mg/kg sc) or given saline as drinking water UAER and PAC decreased to very low levels. Restriction of dietary sodium for 5 weeks increased UAER and PAC 60-fold and 100-fold, respectively. Treatment with ACTH (250 or 500 microng/kg iv) stimulated UAER 8 h following injection and PAC 1 h after injection. In rats treated with a single dose of furosemide (25 mg/kg sc) PAC increased to maximal values within 90 min and reached control values within 24 h. Twenty-four hours-UAER also increased after furosemide treatment. UAER paralleled PAC under all experimental conditions tested. Therefore, our results suggest that UAER is a reliable index of the activity of the renin-angiotensin-aldosterone system in rats under conditions of low and high aldosterone secretion. Measurement of UAER is a useful tool for studies on aldosterone levels in rats over a long period of time.", "contents": "Urinary aldosterone excretion rate and plasma aldosterone concentration in the rat: effect of ACTH, DOC, furosemide and of changes in sodium balance. In rats kept under standard conditions urinary aldosterone exretion rate (UAER) and plasma aldosterone concentration (PAC) showed a circadian rhythm with peak values at the beginning of the dark perioith a single dose of DOC (2 mg/kg sc) or given saline as drinking water UAER and PAC decreased to very low levels. Restriction of dietary sodium for 5 weeks increased UAER and PAC 60-fold and 100-fold, respectively. Treatment with ACTH (250 or 500 microng/kg iv) stimulated UAER 8 h following injection and PAC 1 h after injection. In rats treated with a single dose of furosemide (25 mg/kg sc) PAC increased to maximal values within 90 min and reached control values within 24 h. Twenty-four hours-UAER also increased after furosemide treatment. UAER paralleled PAC under all experimental conditions tested. Therefore, our results suggest that UAER is a reliable index of the activity of the renin-angiotensin-aldosterone system in rats under conditions of low and high aldosterone secretion. Measurement of UAER is a useful tool for studies on aldosterone levels in rats over a long period of time."}
{"id": "PMID:193336", "title": "Effect of local or parenteral application of ACTH or hydrocortisone on bovine corpus luteum function.", "content": "Studies were conducted to determine the effect on corpus luteum (CL) function of ACTH or hydrocortisone administered by ovarian perfusion on day 11 of the oestrous cycle or by carotid infusion on days 2-9 of the oestrous cycle. No significant local effects on CL function were observed during the ovarian perfusion study. Continuous carotid infusion of ACTH or hydrocortisone on days 2-9 resulted in a decreased slope of the progesterone increase during the infusion period. However, no difference in plasma progesterone level on days 9-11 between control and treated cycles was detected and there was no difference between treated and control CL at day 11 with regard to CL weight or progesterone content. The data suggest a possible direct effect of hydrocortisone on either the hypothalamus or pituitary which results in decreased progesterone secretion but not CL development. No residual effect was observed.", "contents": "Effect of local or parenteral application of ACTH or hydrocortisone on bovine corpus luteum function. Studies were conducted to determine the effect on corpus luteum (CL) function of ACTH or hydrocortisone administered by ovarian perfusion on day 11 of the oestrous cycle or by carotid infusion on days 2-9 of the oestrous cycle. No significant local effects on CL function were observed during the ovarian perfusion study. Continuous carotid infusion of ACTH or hydrocortisone on days 2-9 resulted in a decreased slope of the progesterone increase during the infusion period. However, no difference in plasma progesterone level on days 9-11 between control and treated cycles was detected and there was no difference between treated and control CL at day 11 with regard to CL weight or progesterone content. The data suggest a possible direct effect of hydrocortisone on either the hypothalamus or pituitary which results in decreased progesterone secretion but not CL development. No residual effect was observed."}
{"id": "PMID:193333", "title": "Clinical and virological findings in patients with cytologically diagnosed gynecologic herpes simplex infections.", "content": "Amoung 57,117 routinely collected Papanicolaou smears from the female genital tract there were 90 slides (0.16%) from 85 patients on which a cytologic diagnosis of herpes simplex virus (HSV) infection was made. The characteristic cytologic changes occurred predominantly on the ectocervical part of the smears. The changes were transient but occasionally remained detectable on the corresponding histologic specimens up to 2.5 months. Viral isolation was successful in a majority of cases when performed simultaneously with or less than a week after the cytologic diagnosis. The rate of success rapidly decreased thereafter. Positive fluorescent antibody assays of viral antigens on cytologic smears behaved similarly. Cases with apparent primary infection as well as with secondary infection (recurrences) were included in the material but no differences in the morphology of virally altered cells and be found, indicating that primary and secondary infections could not be distinguished on this basis. There were significantly more cytologic dysplastic changes as well as assorted micro-organism infections in the HSV group as compared to the controls.", "contents": "Clinical and virological findings in patients with cytologically diagnosed gynecologic herpes simplex infections. Amoung 57,117 routinely collected Papanicolaou smears from the female genital tract there were 90 slides (0.16%) from 85 patients on which a cytologic diagnosis of herpes simplex virus (HSV) infection was made. The characteristic cytologic changes occurred predominantly on the ectocervical part of the smears. The changes were transient but occasionally remained detectable on the corresponding histologic specimens up to 2.5 months. Viral isolation was successful in a majority of cases when performed simultaneously with or less than a week after the cytologic diagnosis. The rate of success rapidly decreased thereafter. Positive fluorescent antibody assays of viral antigens on cytologic smears behaved similarly. Cases with apparent primary infection as well as with secondary infection (recurrences) were included in the material but no differences in the morphology of virally altered cells and be found, indicating that primary and secondary infections could not be distinguished on this basis. There were significantly more cytologic dysplastic changes as well as assorted micro-organism infections in the HSV group as compared to the controls."}
{"id": "PMID:193337", "title": "A simple and rapid method to measure non-protein-bound fractions of cortisol, testosterone and oestradiol by equilibrium dialysis: comparison with centrifugal filtration.", "content": "A simple method for measuring the free, non-protein-bound steroid fraction in plasma by equilibrium dialysis is described. The alteration occurring in the volume of the inner phase (undiluted plasma) is corrected by the difference in weight before and after dialysis. Total cortisol was determined by radioimmunoassay. Although it is not possible to differentiate between values for total cortisol after ACTH stimulation (242.2+/-shing's syndrome (n: 15)), and women treated with oestrogens (211.8+/-42.0 ng/ml (n: 20)), there were significant differences for free cortisol (ACTH stimulation: 29.3+/-5.6 ng/ml; Cushing's syndrome: 31.5+/-8.6 ng/ml; women under increased oestrogenic activity: 10.0+/-2.1 ng/ml; pregnant women: 13.7+/-5.1 ng/ml plasma). Compared with normal values for healthy women and men (9.3+/-1.4 ng/ml), women with increased oestrogenic activity showed slight elevations of free cortisol. Compared to cortisol, the percentage of dialysable testosterone and oestradiol was lower in women than in men (1.57 vs. 2.08% for testosterone and 1.68 vs. 2.15% for oestradiol). In healthy men the concentration of free steroid was 13.1+/-1.0 ng free testosterone/100 ml plasma (0.44+/-0.045 pg free oestradiol/ml plasma), in healthy women 0.64+/-0.07 ng/100 ml (0.98+/-0.10 pg/ml) and in women receiving oestrogens 0.37+/-0.04 ng/100 ml (0.01+/-0.015 pg/ml). When the method described here for determing the free fractions of cortisol (n: 45), oestradiol (n: 18) and testosterone (n: 18) at 37 degrees C is compared with the method of centrifugal filtration, the correlation was r: 0.80 r: 0.86 and r: 0.91, respectively. In practice, equilibrium dialysis with undiluted plasma is simple, fast and can be applied to all steroid hormones. It allows direct measurements of non-protein-bound steroids under nearly physiological conditions.", "contents": "A simple and rapid method to measure non-protein-bound fractions of cortisol, testosterone and oestradiol by equilibrium dialysis: comparison with centrifugal filtration. A simple method for measuring the free, non-protein-bound steroid fraction in plasma by equilibrium dialysis is described. The alteration occurring in the volume of the inner phase (undiluted plasma) is corrected by the difference in weight before and after dialysis. Total cortisol was determined by radioimmunoassay. Although it is not possible to differentiate between values for total cortisol after ACTH stimulation (242.2+/-shing's syndrome (n: 15)), and women treated with oestrogens (211.8+/-42.0 ng/ml (n: 20)), there were significant differences for free cortisol (ACTH stimulation: 29.3+/-5.6 ng/ml; Cushing's syndrome: 31.5+/-8.6 ng/ml; women under increased oestrogenic activity: 10.0+/-2.1 ng/ml; pregnant women: 13.7+/-5.1 ng/ml plasma). Compared with normal values for healthy women and men (9.3+/-1.4 ng/ml), women with increased oestrogenic activity showed slight elevations of free cortisol. Compared to cortisol, the percentage of dialysable testosterone and oestradiol was lower in women than in men (1.57 vs. 2.08% for testosterone and 1.68 vs. 2.15% for oestradiol). In healthy men the concentration of free steroid was 13.1+/-1.0 ng free testosterone/100 ml plasma (0.44+/-0.045 pg free oestradiol/ml plasma), in healthy women 0.64+/-0.07 ng/100 ml (0.98+/-0.10 pg/ml) and in women receiving oestrogens 0.37+/-0.04 ng/100 ml (0.01+/-0.015 pg/ml). When the method described here for determing the free fractions of cortisol (n: 45), oestradiol (n: 18) and testosterone (n: 18) at 37 degrees C is compared with the method of centrifugal filtration, the correlation was r: 0.80 r: 0.86 and r: 0.91, respectively. In practice, equilibrium dialysis with undiluted plasma is simple, fast and can be applied to all steroid hormones. It allows direct measurements of non-protein-bound steroids under nearly physiological conditions."}
{"id": "PMID:193338", "title": "Triodothyronine and thyroxine nuclear receptors in lyphocytes from normal, hyper- and hypothyroid subjects.", "content": "In an investigation of thyroxine (T4) and triiodothyronine (T3) receptors in humans, the lymphocyte was chosen as the target cell. This study was performed to elucidate whether T3 and T4 bind to different receptors, if T4 is bound only after conversion into T3, and whether there is any modification of the receptors in hyper- and hypothyroidism. Lymphocytes were found to possess a high-affinity, limited-capacity bindings sites for both T4 and T3. The mean equilibrium affinity constant (Ka) was 2.28-10(10 +/- 0.21 m-1 for T3, and 0.98 - 10(10) +/- 0.16 m-1 for T4. The mean number of saturable binding sites was 115 for T3, and 102 for T4. The binding capacities and affinities also determined in the lymphocyte nuclei isolated after incubation of the intact cell, were similar to those observed in the intact cells. In competition experiments, labelled T4 was as readily displaced by T3 as by T4 itself, whereas labelled T3 was displaced only by a 40 times higher concentration of T4 than T3. These observations suggest identical receptors for the two hormones and a binding of T4 as such, provided it is not in competition with T3. In lymphocytes from hyperthyroid patients, receptor affinities and numbers remained unchanged. In lymphocytes from hypothyroid patients, the affinity was normal, but the mean number of T3 binding sites was increased to 310 (P less than 0.0001), to return to normal after a few months of treatment.", "contents": "Triodothyronine and thyroxine nuclear receptors in lyphocytes from normal, hyper- and hypothyroid subjects. In an investigation of thyroxine (T4) and triiodothyronine (T3) receptors in humans, the lymphocyte was chosen as the target cell. This study was performed to elucidate whether T3 and T4 bind to different receptors, if T4 is bound only after conversion into T3, and whether there is any modification of the receptors in hyper- and hypothyroidism. Lymphocytes were found to possess a high-affinity, limited-capacity bindings sites for both T4 and T3. The mean equilibrium affinity constant (Ka) was 2.28-10(10 +/- 0.21 m-1 for T3, and 0.98 - 10(10) +/- 0.16 m-1 for T4. The mean number of saturable binding sites was 115 for T3, and 102 for T4. The binding capacities and affinities also determined in the lymphocyte nuclei isolated after incubation of the intact cell, were similar to those observed in the intact cells. In competition experiments, labelled T4 was as readily displaced by T3 as by T4 itself, whereas labelled T3 was displaced only by a 40 times higher concentration of T4 than T3. These observations suggest identical receptors for the two hormones and a binding of T4 as such, provided it is not in competition with T3. In lymphocytes from hyperthyroid patients, receptor affinities and numbers remained unchanged. In lymphocytes from hypothyroid patients, the affinity was normal, but the mean number of T3 binding sites was increased to 310 (P less than 0.0001), to return to normal after a few months of treatment."}
{"id": "PMID:193339", "title": "Significance of 17alpha OH progesterone assay in the evaluation of ovarian and adrenal function.", "content": "Plasma 17alpha OH progesterone was assayed radioimmunologically, using an anti-17-OH-progesterone BSA antiserum as specific binding antigen. The method consisted in extracting steroids with ethyl ether from 1 ml plasm (to which 17alpha OH progesterone-1,2-3H had been added for the assessment of losses); the extract was then submitted to chromatography on a Sephadex LH-20 column, antiserum was added and the free steroid was separated from the bound form by Charcoal-dextran. Average recovery of 17alpha OH progesterone-1,2-3H was 75+/-5%. Minimum sensitivity of the method oscillated about 7-10 pg. MIF (Method Interfering Factors) were evaluated. The method was used for the assay of 17alpha OH progesterone plasma levels during normal menstrual cycles, in women undergoing ovarian stimulation with HMG and HCG in the follicular and luteal phase respectively. Finally, changes of plasma 17alpha OH progesterone levels were assessed during adrenal stimulation and suppression in various stages of the menstrual cycle.", "contents": "Significance of 17alpha OH progesterone assay in the evaluation of ovarian and adrenal function. Plasma 17alpha OH progesterone was assayed radioimmunologically, using an anti-17-OH-progesterone BSA antiserum as specific binding antigen. The method consisted in extracting steroids with ethyl ether from 1 ml plasm (to which 17alpha OH progesterone-1,2-3H had been added for the assessment of losses); the extract was then submitted to chromatography on a Sephadex LH-20 column, antiserum was added and the free steroid was separated from the bound form by Charcoal-dextran. Average recovery of 17alpha OH progesterone-1,2-3H was 75+/-5%. Minimum sensitivity of the method oscillated about 7-10 pg. MIF (Method Interfering Factors) were evaluated. The method was used for the assay of 17alpha OH progesterone plasma levels during normal menstrual cycles, in women undergoing ovarian stimulation with HMG and HCG in the follicular and luteal phase respectively. Finally, changes of plasma 17alpha OH progesterone levels were assessed during adrenal stimulation and suppression in various stages of the menstrual cycle."}
{"id": "PMID:193340", "title": "Neither cyclic AMP nor cyclic GMP appear to mediate antral gastrin release in the dog.", "content": "To evaluate whether cyclic nucleotides play a role as mediators in antral gastrin release, the following in vivo experiments were performed in dogs. An antral pouch was constructed and the rest of the stomach, the pancreas and small and large intestine were resected. A gastric artery supplying the pouch was cannulated, and after a basal period with saline infusion either dibutyryl cyclic 3',5'-adenosine monophosphate (cyclic AMP, 0.2 mg per kg per min), dibutyryl cyclic 3',5'-guanosine monophosphate (cyclic GMP, 0.05 mg per kg per min) or saline were infused over a period of 60 min. To prove the viability of the pouch and to show its ability to release gastrin with proper stimulation, bethanechol chloride (urecholine) was infused into the gastric artery at the end of the experiment. Blood samples were taken from the portal vein and assayed for gastrin. Neither cyclic AMP nor cyclic GMP infusion was found to increase portal gastrin concentration to a significant degree. A marked increase in portal gastrin concentration however, was observed when bethanechol chloride was infused. These studies lend no support to the thesis that cyclic nucleotides mediate gastrin release in the dog.", "contents": "Neither cyclic AMP nor cyclic GMP appear to mediate antral gastrin release in the dog. To evaluate whether cyclic nucleotides play a role as mediators in antral gastrin release, the following in vivo experiments were performed in dogs. An antral pouch was constructed and the rest of the stomach, the pancreas and small and large intestine were resected. A gastric artery supplying the pouch was cannulated, and after a basal period with saline infusion either dibutyryl cyclic 3',5'-adenosine monophosphate (cyclic AMP, 0.2 mg per kg per min), dibutyryl cyclic 3',5'-guanosine monophosphate (cyclic GMP, 0.05 mg per kg per min) or saline were infused over a period of 60 min. To prove the viability of the pouch and to show its ability to release gastrin with proper stimulation, bethanechol chloride (urecholine) was infused into the gastric artery at the end of the experiment. Blood samples were taken from the portal vein and assayed for gastrin. Neither cyclic AMP nor cyclic GMP infusion was found to increase portal gastrin concentration to a significant degree. A marked increase in portal gastrin concentration however, was observed when bethanechol chloride was infused. These studies lend no support to the thesis that cyclic nucleotides mediate gastrin release in the dog."}
{"id": "PMID:193341", "title": "The effect of ACTH and cortisone on the behaviour of arylsulphatases in the salivary glands of white rat.", "content": "Many reports show (DAVIDOFF 1973, HOOK et al. 1970, KOSTULAK 1974, MILSOM 1970, THYBERG 1972) that arylsulphatases are widely present in the tissues of many animals, and a high activity has been observed, among other things, in secretory epithelia (HSU and TAPPEL 1965, KOSTULAK 1975, MAKITA and SANBORN 1971). The occurrence of these enzymes some authors connect with the metabolism of sulphated polysaccharides (DOGSON 1968, MARTIN et al. 1969, MEYER 1969). However, although the specificity and intracellular localization of these enzymes in different tissues have been described perviously, there are only a few reports about their localization in the salivary gland, and the functional role of arylsulphatases in the physiological function of the salivary glands. The observations reported by numerous authors (KOZLOWSKA 1973, KYAW and MELLORS 1972, SACHS and DE DUVE 1962), and in ours studies (KOSTULAK 1975) indicate that the activity of lysosomal enzymes, including arylsulphatases, is modified by steroid hormones. Moreover, it is known that these hormones have an influence on the composition and nature of the carbohydrate-protein complexes produced by the salivary glands (KOFOED et al. 1973, KOSTULAK et al. 1972). Therefore it seemed interesting to examine the behaviour of arylsolphatases in the salivary glands after treatment with large doses of ACTH and cortisone, and find if there is any correlation between the activity of these enzymes and the changes of sulphated polysaccharides observed previously in the cell of the salivary glands after applying ACTH and cortisone.", "contents": "The effect of ACTH and cortisone on the behaviour of arylsulphatases in the salivary glands of white rat. Many reports show (DAVIDOFF 1973, HOOK et al. 1970, KOSTULAK 1974, MILSOM 1970, THYBERG 1972) that arylsulphatases are widely present in the tissues of many animals, and a high activity has been observed, among other things, in secretory epithelia (HSU and TAPPEL 1965, KOSTULAK 1975, MAKITA and SANBORN 1971). The occurrence of these enzymes some authors connect with the metabolism of sulphated polysaccharides (DOGSON 1968, MARTIN et al. 1969, MEYER 1969). However, although the specificity and intracellular localization of these enzymes in different tissues have been described perviously, there are only a few reports about their localization in the salivary gland, and the functional role of arylsulphatases in the physiological function of the salivary glands. The observations reported by numerous authors (KOZLOWSKA 1973, KYAW and MELLORS 1972, SACHS and DE DUVE 1962), and in ours studies (KOSTULAK 1975) indicate that the activity of lysosomal enzymes, including arylsulphatases, is modified by steroid hormones. Moreover, it is known that these hormones have an influence on the composition and nature of the carbohydrate-protein complexes produced by the salivary glands (KOFOED et al. 1973, KOSTULAK et al. 1972). Therefore it seemed interesting to examine the behaviour of arylsolphatases in the salivary glands after treatment with large doses of ACTH and cortisone, and find if there is any correlation between the activity of these enzymes and the changes of sulphated polysaccharides observed previously in the cell of the salivary glands after applying ACTH and cortisone."}
{"id": "PMID:193342", "title": "Infantile chronic peripheral neuropathy with giant axons. Report of a case.", "content": "An 8-year-old boy with a slowly progressive motor neuropathy is described. The first signs appeared at the age of 3 years. Histological examination of the sural nerve showed the presence of numerous segmental axonal swellings and features of demyelination as well as remyelination. These enlargements were filled with irregularly orientated 10 nm filaments. The case resembled the previously described cases of giant axonal neuropathy but differed from them in absence of kinky hair.", "contents": "Infantile chronic peripheral neuropathy with giant axons. Report of a case. An 8-year-old boy with a slowly progressive motor neuropathy is described. The first signs appeared at the age of 3 years. Histological examination of the sural nerve showed the presence of numerous segmental axonal swellings and features of demyelination as well as remyelination. These enlargements were filled with irregularly orientated 10 nm filaments. The case resembled the previously described cases of giant axonal neuropathy but differed from them in absence of kinky hair."}
{"id": "PMID:193343", "title": "Department of Neurology, Northwestern University Medical School, Chicago, Illinois.", "content": "A case of non-progressive congenital myopathy is described in which there was absence of muscles and scapulo-peroneal distribution of weakness. The muscle biopsy showed preferential atrophy of Type I fibers and subsarcolemal bodies. These bodies were composed of an acidic protein with sulphahydryl groups which showed acid stable adenosine triphosphatase activity. The possibility of a maturational arrest as a cause is presented.", "contents": "Department of Neurology, Northwestern University Medical School, Chicago, Illinois. A case of non-progressive congenital myopathy is described in which there was absence of muscles and scapulo-peroneal distribution of weakness. The muscle biopsy showed preferential atrophy of Type I fibers and subsarcolemal bodies. These bodies were composed of an acidic protein with sulphahydryl groups which showed acid stable adenosine triphosphatase activity. The possibility of a maturational arrest as a cause is presented."}
{"id": "PMID:193344", "title": "Filamentous and multilamellated cytoplasmic inclusions in progressive multifocal leukoencephalopathy.", "content": "Inclusions identical to those described in multiple sclerosis (MS) brain by Prineas (1975) have been seen by ultrastructural study of cerebral tissue in two elsewhere reported cases of Progressive Multifocal Leukoencephalopathy (PML). The meaning of these formations, which have been suggested to be related to a special process of demyelination in MS, is discussed in the light of the hypotheses concerning the demyelination mechanism in  PML. Whatever might be their significance, these cytoplasmic non viral inclusions are not specific for MS.", "contents": "Filamentous and multilamellated cytoplasmic inclusions in progressive multifocal leukoencephalopathy. Inclusions identical to those described in multiple sclerosis (MS) brain by Prineas (1975) have been seen by ultrastructural study of cerebral tissue in two elsewhere reported cases of Progressive Multifocal Leukoencephalopathy (PML). The meaning of these formations, which have been suggested to be related to a special process of demyelination in MS, is discussed in the light of the hypotheses concerning the demyelination mechanism in  PML. Whatever might be their significance, these cytoplasmic non viral inclusions are not specific for MS."}
{"id": "PMID:193345", "title": "Microprobe scanning of normal and pathological human peripheral nerve.", "content": "The localization of calcium (Ca) and phosphorus (P) by scanning with the electron microprobe of Casting, provides a morphological outline of the normal nerve which can be used qualitatively and quantitatively for comparison with abnormal nerves. The normal saphenous nerves of eight cadavers and the abnormal saphenous nerves of two cases of diabetic neuropathy, were scanned and the results compared.", "contents": "Microprobe scanning of normal and pathological human peripheral nerve. The localization of calcium (Ca) and phosphorus (P) by scanning with the electron microprobe of Casting, provides a morphological outline of the normal nerve which can be used qualitatively and quantitatively for comparison with abnormal nerves. The normal saphenous nerves of eight cadavers and the abnormal saphenous nerves of two cases of diabetic neuropathy, were scanned and the results compared."}
{"id": "PMID:193346", "title": "The role of the subependymal plate in avian sarcoma virus brain tumor induction: comparison of incipient tumors in neonatal and adult rats.", "content": "F-344 rats were inoculated intracerebrally at 1 and at 133 days of age with the Bratislava-77 strain of avian sarcoma virus. Groups of rats were sequentially sacrificed following inoculation so that early stages of microtumor formation could be evaluated. In neonatally inoculated rats incipient tumors developed in the subependymal region of the lateral ventricles in close juxtaposition to clusters of poorly differentiated germinal cells. Among these animals microtumors were detected as soon as 2 weeks after inoculation; by 4 weeks post-inoculation all rats inoculated at 1 day of age had tumors. In contrast among rats inoculated as adults incipient tumors developed in the cerebral cortex away from the subependymal region but adjacent to the locus of inoculation. Incipient tumors were uncommon in rats inoculated as adults during the first 2 months after inoculation.", "contents": "The role of the subependymal plate in avian sarcoma virus brain tumor induction: comparison of incipient tumors in neonatal and adult rats. F-344 rats were inoculated intracerebrally at 1 and at 133 days of age with the Bratislava-77 strain of avian sarcoma virus. Groups of rats were sequentially sacrificed following inoculation so that early stages of microtumor formation could be evaluated. In neonatally inoculated rats incipient tumors developed in the subependymal region of the lateral ventricles in close juxtaposition to clusters of poorly differentiated germinal cells. Among these animals microtumors were detected as soon as 2 weeks after inoculation; by 4 weeks post-inoculation all rats inoculated at 1 day of age had tumors. In contrast among rats inoculated as adults incipient tumors developed in the cerebral cortex away from the subependymal region but adjacent to the locus of inoculation. Incipient tumors were uncommon in rats inoculated as adults during the first 2 months after inoculation."}
{"id": "PMID:193347", "title": "[Electron microscopic study of nerve, muscle and skin lesions induced by perhexiline maleate (author's transl)].", "content": "The pathological findings in four nerves and muscles and in one skin biopsies from four patients treated with perhexiline maleate for angina pectoris are reported. In every case, a muscular denervation atrophy and a decrease in the large diameter myelinated fibers were observed. Only one case showed a decrease of the total number of myelinated fibers, on quantitative studies. The electron microscopic study of each nerve displayed findings consistent with a predominant schwannian degeneration, associated with a few onion bulbs formations and, in two cases, with a mild wallerian degeneration. The most striking finding consisted in  the presence of polymorphous membrane-bound inclusions reminding the morphology of lysosomal complex lipids. These structures were very abundant in Schwann cells, but they were seen also in fibrocytes, endothelial and pericytic cells. Similar inclusions were present in the single muscle and skin biopsies studied by electron microscopy. In the muscle, they were seen in muscular cells as well as in endothelial and pericytic cells. In the skin, similar inclusions were observed in endothelial, smooth muscle and sweat gland cells. These inclusions were difficult to identify in one micron thick sections, emphazing the need of ultrastructural study for diagnostic purposes.", "contents": "[Electron microscopic study of nerve, muscle and skin lesions induced by perhexiline maleate (author's transl)]. The pathological findings in four nerves and muscles and in one skin biopsies from four patients treated with perhexiline maleate for angina pectoris are reported. In every case, a muscular denervation atrophy and a decrease in the large diameter myelinated fibers were observed. Only one case showed a decrease of the total number of myelinated fibers, on quantitative studies. The electron microscopic study of each nerve displayed findings consistent with a predominant schwannian degeneration, associated with a few onion bulbs formations and, in two cases, with a mild wallerian degeneration. The most striking finding consisted in  the presence of polymorphous membrane-bound inclusions reminding the morphology of lysosomal complex lipids. These structures were very abundant in Schwann cells, but they were seen also in fibrocytes, endothelial and pericytic cells. Similar inclusions were present in the single muscle and skin biopsies studied by electron microscopy. In the muscle, they were seen in muscular cells as well as in endothelial and pericytic cells. In the skin, similar inclusions were observed in endothelial, smooth muscle and sweat gland cells. These inclusions were difficult to identify in one micron thick sections, emphazing the need of ultrastructural study for diagnostic purposes."}
{"id": "PMID:193352", "title": "I-cell disease (mucolipidosis 11). Pathological and biochemical studies of an autopsy case.", "content": "An autopsy case of I-cell disease was examined by histological, histochemical, ultrastructural and biochemical methods. Cultured fibroblasts contained numerous PAS- and oil-red O positive granules consistent with lysosomes. The beta-galactosidase activity was specifically low in liver of the patient. The fiboblast-like cells including the cardiac valves, periosteum and stromal cells of the organs were closely similar to those found in mucopolysaccharidoses histochemically as well as ultrastructurally. Lipid-like materials were observed massively in the myocardium and in the neurons of spinal ganglia, and from these organs excessive amount of ceramide tri-hexosides (CTH) was extracted. In a few hepatocytes the dense membrane-bound bodies suggestive of lipids were found by electron microscopy. Swollen glomerular epithelium contained strongly colloidal-iron positive material, but the amount of mucopolysaccharides in kidney was not elevated. In this paper, the relationship among the morphology, the material stored and the enzymes was discussed.", "contents": "I-cell disease (mucolipidosis 11). Pathological and biochemical studies of an autopsy case. An autopsy case of I-cell disease was examined by histological, histochemical, ultrastructural and biochemical methods. Cultured fibroblasts contained numerous PAS- and oil-red O positive granules consistent with lysosomes. The beta-galactosidase activity was specifically low in liver of the patient. The fiboblast-like cells including the cardiac valves, periosteum and stromal cells of the organs were closely similar to those found in mucopolysaccharidoses histochemically as well as ultrastructurally. Lipid-like materials were observed massively in the myocardium and in the neurons of spinal ganglia, and from these organs excessive amount of ceramide tri-hexosides (CTH) was extracted. In a few hepatocytes the dense membrane-bound bodies suggestive of lipids were found by electron microscopy. Swollen glomerular epithelium contained strongly colloidal-iron positive material, but the amount of mucopolysaccharides in kidney was not elevated. In this paper, the relationship among the morphology, the material stored and the enzymes was discussed."}
{"id": "PMID:193353", "title": "Immunohistological study on the ACTH producing islet cell carcinoma of the pancreas.", "content": "ACTH producing cells in islet cell carcinoma associated with Cushing's syndrome were studied by an improved immunoperoxidase as well as immunofluorescence technique. The cells which contained ACTH antigen were distributed throughout the tumor tissue of both primary and metastatic lesions in rather small numbers. In the small cancer nests they were present in an irregular or mosaic pattern and, on the contrary, they tend to line along the margin in the larger nests. The intracytoplasmic localization of the ACTH antigen was characteristically demonstrated in the infranuclear area of the tumor cells, closely simulating that of the argentaffin granules of the enterochromaffin cells. The electron microscopic observation identified membrane enclosed, cored granules, 200-300 nm in diameter, present in clusters in the infranuclear area of some tumor cells, which were considered corresponding well to the ACTH positive cells in immune staining.", "contents": "Immunohistological study on the ACTH producing islet cell carcinoma of the pancreas. ACTH producing cells in islet cell carcinoma associated with Cushing's syndrome were studied by an improved immunoperoxidase as well as immunofluorescence technique. The cells which contained ACTH antigen were distributed throughout the tumor tissue of both primary and metastatic lesions in rather small numbers. In the small cancer nests they were present in an irregular or mosaic pattern and, on the contrary, they tend to line along the margin in the larger nests. The intracytoplasmic localization of the ACTH antigen was characteristically demonstrated in the infranuclear area of the tumor cells, closely simulating that of the argentaffin granules of the enterochromaffin cells. The electron microscopic observation identified membrane enclosed, cored granules, 200-300 nm in diameter, present in clusters in the infranuclear area of some tumor cells, which were considered corresponding well to the ACTH positive cells in immune staining."}
{"id": "PMID:193354", "title": "Viral placentitis - a case report.", "content": "A case of viral placentitis, in a 20 year-old pregnant woman suffering from chronic glomerulonephritis, was presented. In light microscopic findings of the placenta, many necrotic foci with intranuclear inclusion - bearing cells revealed in chorionic villi and by electron microscopy numerous immature and mature virus particles, probably herpes simplex were proved in intranuclear inclusion-bearing cells.", "contents": "Viral placentitis - a case report. A case of viral placentitis, in a 20 year-old pregnant woman suffering from chronic glomerulonephritis, was presented. In light microscopic findings of the placenta, many necrotic foci with intranuclear inclusion - bearing cells revealed in chorionic villi and by electron microscopy numerous immature and mature virus particles, probably herpes simplex were proved in intranuclear inclusion-bearing cells."}
{"id": "PMID:193355", "title": "Demonstration of host antigens in the myxovirus memebrane: lysis of virus by antibody and complement.", "content": "Complement-mediated lesions developed in myxovirus membranes in the presence of antibody to host antigens. Intact virions reacted with antibody to the keratosulphate-like host antigen present in the spike layer. Spike-deprived influenza virus reacted in the same way when an antiserum to the Forssman glycolipid was used. The holes in the membrane varied considerably in size, but were otherwise similar to those found in erythrocyte membranes. This immune electron microscopy method proved useful for the localization of host material in viral membranes.", "contents": "Demonstration of host antigens in the myxovirus memebrane: lysis of virus by antibody and complement. Complement-mediated lesions developed in myxovirus membranes in the presence of antibody to host antigens. Intact virions reacted with antibody to the keratosulphate-like host antigen present in the spike layer. Spike-deprived influenza virus reacted in the same way when an antiserum to the Forssman glycolipid was used. The holes in the membrane varied considerably in size, but were otherwise similar to those found in erythrocyte membranes. This immune electron microscopy method proved useful for the localization of host material in viral membranes."}
{"id": "PMID:193356", "title": "Classification of coagulase-negative staphylococci in the diagnostic laboratory.", "content": "One hundred and ninety-eight coagulase-negative staphylococci isolated from urines, blood cultures, and pus samples were classified by means of two identification schemes, and their wall teichoic acids were determined serologically. S. epidermidis, S. saprophyticus, and S. cohnii were identified reliably by the use of five criteria: acid aerobically from sucrose, trehalose, and mannitol, phosphatase production, and sensitivity to novobiocin. Further species, notably S. haemolyticus and S. hominis, could be identified when haemolysis on blood agar plates was included in the criteria group. The investigation shows, that a considerable number of coagulase-negative staphylococci isolated from human specimens belong to species other than S. epidermidis and S. saprophyticus. These staphylococci can cause human infections and should be identified in the diagnostic laboratory. S. epidermidis and S. saprophyticus were found to contain the teichoic acids previously identified in these species. S. cohnii contained the same teichoic acids as S. saprophyticus. No characteristic teichoic acid was demonstrated in the other species, but several strains contained poly C (beta-N-acetylglucosaminylglycerol teichoic acid).", "contents": "Classification of coagulase-negative staphylococci in the diagnostic laboratory. One hundred and ninety-eight coagulase-negative staphylococci isolated from urines, blood cultures, and pus samples were classified by means of two identification schemes, and their wall teichoic acids were determined serologically. S. epidermidis, S. saprophyticus, and S. cohnii were identified reliably by the use of five criteria: acid aerobically from sucrose, trehalose, and mannitol, phosphatase production, and sensitivity to novobiocin. Further species, notably S. haemolyticus and S. hominis, could be identified when haemolysis on blood agar plates was included in the criteria group. The investigation shows, that a considerable number of coagulase-negative staphylococci isolated from human specimens belong to species other than S. epidermidis and S. saprophyticus. These staphylococci can cause human infections and should be identified in the diagnostic laboratory. S. epidermidis and S. saprophyticus were found to contain the teichoic acids previously identified in these species. S. cohnii contained the same teichoic acids as S. saprophyticus. No characteristic teichoic acid was demonstrated in the other species, but several strains contained poly C (beta-N-acetylglucosaminylglycerol teichoic acid)."}
{"id": "PMID:193357", "title": "Alpha-receptor subsensitivity of isolated atria from rats following physical training or repeated ACTH-injections.", "content": "Decreased chronotropic and inotropic sensitivity of isolated atria to phenylephrine but not to isoprenaline was found in rats following repeated physical training by swimming or repeated ACTH-injections. These changes were induced within a week of subjection of animals to these treatments. It is concluded, that these effects are mediated by increased adrenergic activity which results in this subsensitivity of alpha-receptors.", "contents": "Alpha-receptor subsensitivity of isolated atria from rats following physical training or repeated ACTH-injections. Decreased chronotropic and inotropic sensitivity of isolated atria to phenylephrine but not to isoprenaline was found in rats following repeated physical training by swimming or repeated ACTH-injections. These changes were induced within a week of subjection of animals to these treatments. It is concluded, that these effects are mediated by increased adrenergic activity which results in this subsensitivity of alpha-receptors."}
{"id": "PMID:193359", "title": "Effects of ACTH 4-10 on ECT-induced memory dysfunctions.", "content": "Double-blind studies of ACTH 4-10 and placebo were conducted in psychiatric patients receiving bilateral ECT to determine whether the polypeptide exerted anti-amnesic effects. Observations after a single ECT were suggestive of some positive effects, but studies between seizures after five or six ECTs showed no significant drug-placebo differences. Although the findings were largely negative, they do not rule out positive effects of ACTH 4-10 on memory. Possibly the designs and timing of the experiments and/or the dosages of ACTH 4-10 employed were unsuitable for demonstrating such influences.", "contents": "Effects of ACTH 4-10 on ECT-induced memory dysfunctions. Double-blind studies of ACTH 4-10 and placebo were conducted in psychiatric patients receiving bilateral ECT to determine whether the polypeptide exerted anti-amnesic effects. Observations after a single ECT were suggestive of some positive effects, but studies between seizures after five or six ECTs showed no significant drug-placebo differences. Although the findings were largely negative, they do not rule out positive effects of ACTH 4-10 on memory. Possibly the designs and timing of the experiments and/or the dosages of ACTH 4-10 employed were unsuitable for demonstrating such influences."}
{"id": "PMID:193360", "title": "Electron microscopic studies of various cells in the alveolar wall of mice with special reference to spheroid alveolar epithelial cells after intravenous injection of squid-ink (sepia-melanin) solution.", "content": "The effect of an intravenous injection of squid-ink (sepia-melanin) solution on adult mouse spheroid alveolar epithelial cells was observed by the electron microscope. Sepia-melanin particles were seen in all alveolar wall cells examined that seems to suggest the entrance of sepia-melanin particles into the spheroid alveolar epithlial cells from the alveolar blood capillary. In cases of large penetrations of sepia-melanin particles into spheroid alveolar epithelial cells, a greater increase was found in the intramitochondrial granules. In addition, the so-called inclusion body believed to be formed by the degeneration of mitochondria had very high electron density and its quantity was abundant. On the contrary, in cases where the quantity of sepia-melanin entrance into the spheroid alveolar epithelial cell was small, neither an increase of intramitochondrial granules, an increase of the electron density nor an increase in the quantity of specific inclusion body was found.", "contents": "Electron microscopic studies of various cells in the alveolar wall of mice with special reference to spheroid alveolar epithelial cells after intravenous injection of squid-ink (sepia-melanin) solution. The effect of an intravenous injection of squid-ink (sepia-melanin) solution on adult mouse spheroid alveolar epithelial cells was observed by the electron microscope. Sepia-melanin particles were seen in all alveolar wall cells examined that seems to suggest the entrance of sepia-melanin particles into the spheroid alveolar epithlial cells from the alveolar blood capillary. In cases of large penetrations of sepia-melanin particles into spheroid alveolar epithelial cells, a greater increase was found in the intramitochondrial granules. In addition, the so-called inclusion body believed to be formed by the degeneration of mitochondria had very high electron density and its quantity was abundant. On the contrary, in cases where the quantity of sepia-melanin entrance into the spheroid alveolar epithelial cell was small, neither an increase of intramitochondrial granules, an increase of the electron density nor an increase in the quantity of specific inclusion body was found."}
{"id": "PMID:193361", "title": "Tissue localization of C1q in HBs antigen positive liver disease patients by direct immunofluorescent technique.", "content": "Tissue localization of a subcomponent of the first component of complement (CLq) was examined in one postmortem case of HBs antigen (HBs Ag) positive hepatocellular carcinoma and in six cases of chronic hepatitis from liver biopsy specimens. The direct immunofluorescent method was used after fixation with 2% para-formaldehyde in concentrated ammonium sulfate. CLq localization was found in collagen fibers and the cytoplasm of fibroblasts in the connective tissues of specimens examined. The localization was particularly marked in the region of the fundal glands of the gastric wall. Apart from collagen fibers, other sites of localization included the surface membrane of lymphocytes, especially those cells of the mesenteric lymph nodes. In HBs Ag positive specimens, immune deposit-like substances appeared localized intra-hepatically and in the renal glomeruli. Since C3 and C4 were identified concomitantly, it indicates that these substances were indeed immune diposits. Despite the finding that C3 and C4 were identified together in the hepatic cell cytoplasm, C1q itself was not demonstrated in all hepatic cell cytoplasms.", "contents": "Tissue localization of C1q in HBs antigen positive liver disease patients by direct immunofluorescent technique. Tissue localization of a subcomponent of the first component of complement (CLq) was examined in one postmortem case of HBs antigen (HBs Ag) positive hepatocellular carcinoma and in six cases of chronic hepatitis from liver biopsy specimens. The direct immunofluorescent method was used after fixation with 2% para-formaldehyde in concentrated ammonium sulfate. CLq localization was found in collagen fibers and the cytoplasm of fibroblasts in the connective tissues of specimens examined. The localization was particularly marked in the region of the fundal glands of the gastric wall. Apart from collagen fibers, other sites of localization included the surface membrane of lymphocytes, especially those cells of the mesenteric lymph nodes. In HBs Ag positive specimens, immune deposit-like substances appeared localized intra-hepatically and in the renal glomeruli. Since C3 and C4 were identified concomitantly, it indicates that these substances were indeed immune diposits. Despite the finding that C3 and C4 were identified together in the hepatic cell cytoplasm, C1q itself was not demonstrated in all hepatic cell cytoplasms."}
{"id": "PMID:193358", "title": "After-care services for schizophrenic patients.", "content": "The multi-dimensional therapeutic requirements of an aftercare programme for schizophrenic patients are emphasized. The manipulation of a single variable, e.g. a drug, without paying attention to the social, demographic and ecological context of the programme, may lead not only to disappointing results but to non-valid comparisons of effectiveness between results in different centers. In face of the multiple contraints, the after-care of the schizophrenic patient will long remain a task of therapeutic skill.", "contents": "After-care services for schizophrenic patients. The multi-dimensional therapeutic requirements of an aftercare programme for schizophrenic patients are emphasized. The manipulation of a single variable, e.g. a drug, without paying attention to the social, demographic and ecological context of the programme, may lead not only to disappointing results but to non-valid comparisons of effectiveness between results in different centers. In face of the multiple contraints, the after-care of the schizophrenic patient will long remain a task of therapeutic skill."}
{"id": "PMID:193364", "title": "Use of elution marker for the intratypic characterization of poliovirus strains.", "content": "Elution marker was used for intratypic characterization of poliovirus strains with Al(OH)3 gel as adsorbent. The virion suspensions to be tested were partially purified by chromatography and labelled with 32P. In the labelled preparations of wild virus strains practically all radioactivity was found in virus-specific bond, whereas in those of the vaccine strains and isolates of vaccine origin a considerable, but variable, proportion of the activity was bound to residual cell components. For this reason, the EC50 value (i.e. the phosphate molarity corresponding to the 50% adsorption equilibrium of virions), for the vaccine and vaccine-like strains showed a wide scattering. The activity bound to cell components was removable from the gel with 0.005 M phosphate buffer, whereas the elution maxima for all the poliovirus strains examined so far were over 0.02 M. The elution marker was calculated for 25 type-2 and 30 type-3 strains, all isolated during or soon after vaccination periods from cases suspect of poliomyelitis, both with and without taking into account the cell-bound activity. In the latter case, the EC50 values agreed with that for the corresponding reference vaccine strain much better than in the former; furthermore, the type-2 reference vaccine strain and the type-2 isolates, indistinguishable from the wild reference strain by the original method, could easily be differentiated on the basis of the corrected EC50 value. The possibility that the lack of an appreciable proportion of cell-bound radioactivity may reflect the pathogenicity of poliovirus strains is discussed.", "contents": "Use of elution marker for the intratypic characterization of poliovirus strains. Elution marker was used for intratypic characterization of poliovirus strains with Al(OH)3 gel as adsorbent. The virion suspensions to be tested were partially purified by chromatography and labelled with 32P. In the labelled preparations of wild virus strains practically all radioactivity was found in virus-specific bond, whereas in those of the vaccine strains and isolates of vaccine origin a considerable, but variable, proportion of the activity was bound to residual cell components. For this reason, the EC50 value (i.e. the phosphate molarity corresponding to the 50% adsorption equilibrium of virions), for the vaccine and vaccine-like strains showed a wide scattering. The activity bound to cell components was removable from the gel with 0.005 M phosphate buffer, whereas the elution maxima for all the poliovirus strains examined so far were over 0.02 M. The elution marker was calculated for 25 type-2 and 30 type-3 strains, all isolated during or soon after vaccination periods from cases suspect of poliomyelitis, both with and without taking into account the cell-bound activity. In the latter case, the EC50 values agreed with that for the corresponding reference vaccine strain much better than in the former; furthermore, the type-2 reference vaccine strain and the type-2 isolates, indistinguishable from the wild reference strain by the original method, could easily be differentiated on the basis of the corrected EC50 value. The possibility that the lack of an appreciable proportion of cell-bound radioactivity may reflect the pathogenicity of poliovirus strains is discussed."}
{"id": "PMID:193374", "title": "Studies on the regulation of the biosynthesis of myocardial adenine nucleotides.", "content": "1) Changes in the rates of biosynthesis of adenine nucleotides in rat hearts under various experimental conditions are paralleled by corresponding alterations in the concentration of cyclic AMP. 2) Pentoses and pentitols cause an acceleration of the de novo synthesis of adenine nucleotides in the normal heart and a further amplification of the increase of adenine nucleotide synthesis in isoproterenol-stimulated hearts. 3) The enhancement of de novo synthesis of adenine and nucleotides induced by isoproterenol as well as by pentoses and pentitols appears to be causally related to a greater availability of 5-phos-phoribosyl-1-pyrophosphate.", "contents": "Studies on the regulation of the biosynthesis of myocardial adenine nucleotides. 1) Changes in the rates of biosynthesis of adenine nucleotides in rat hearts under various experimental conditions are paralleled by corresponding alterations in the concentration of cyclic AMP. 2) Pentoses and pentitols cause an acceleration of the de novo synthesis of adenine nucleotides in the normal heart and a further amplification of the increase of adenine nucleotide synthesis in isoproterenol-stimulated hearts. 3) The enhancement of de novo synthesis of adenine and nucleotides induced by isoproterenol as well as by pentoses and pentitols appears to be causally related to a greater availability of 5-phos-phoribosyl-1-pyrophosphate."}
{"id": "PMID:193375", "title": "Immunological aspects of purine metabolism.", "content": "The development of our knowledge of the immune system has been reviewed and evidence presented of the need for a rapid rate of purine synthesis de novo for the proliferative events in this process. The mechanism of the inhibition of the immune system in a model of ADA deficiency has been studied intensively and considerable indirect evidence obtained of adenosine toxicity as a possible mediator of a reversible inhibition of proliferation of T-cells and to a slightly lesser extent B-cells. A secondary inhibition of ADA by inosine accumulation in PNP deficiency is proposed as a unifying hypothesis in which a somewhat lesser adenosine toxicity would inhibit proliferation only only of T-cells. The correction of the immune response by addition of ADA both in vitro and in vivo provides strong evidence in favor of this view. In HPRT deficiency no evidence was found of a gross impairment of the immune system; however, the HPRT enzyme is required for inhibition of the immune response by 6MP in a variety of systems using different mitogenic stimuli.", "contents": "Immunological aspects of purine metabolism. The development of our knowledge of the immune system has been reviewed and evidence presented of the need for a rapid rate of purine synthesis de novo for the proliferative events in this process. The mechanism of the inhibition of the immune system in a model of ADA deficiency has been studied intensively and considerable indirect evidence obtained of adenosine toxicity as a possible mediator of a reversible inhibition of proliferation of T-cells and to a slightly lesser extent B-cells. A secondary inhibition of ADA by inosine accumulation in PNP deficiency is proposed as a unifying hypothesis in which a somewhat lesser adenosine toxicity would inhibit proliferation only only of T-cells. The correction of the immune response by addition of ADA both in vitro and in vivo provides strong evidence in favor of this view. In HPRT deficiency no evidence was found of a gross impairment of the immune system; however, the HPRT enzyme is required for inhibition of the immune response by 6MP in a variety of systems using different mitogenic stimuli."}
{"id": "PMID:193383", "title": "H1 - and H2-receptor mediated responses to histamine on contractility and cyclic AMP of atrial and papillary muscles from guinea-pig hearts.", "content": "On guinea-pig heart we investigated whether cyclic AMP serves as a messenger for H1 - and/or H2-mediated responses to histamine. (1) On papillary muscle histamine elicited positive inotropic responses which were antagonized by burimamide but not by promethazine. The stimulation of H2-receptors was not only associated with an increase in contractility but also with an increase in cAMP. As shown by the time course of effects for 10(-5) M histamine, the maximal increase in cAMP preceded the maximum in contractility. The mechanical and biochemical responses to histamine were potentiated by the phosphodiesterase inhibitor papaverine, but antagonized by burimamide. (2) On the left guinea-pig atrium containing H1-receptors the inotropic response to histamine (10(-5) M) was not accompanied by increases in cAMP at stimulation frequencies of 0.5 and 2 Hz, respectively. In addition, in the presence of papaverine (3 X 10 (-5) M) no change in the cyclic AMP level occurred after application of histamine. Papaverine by itself, however, concomitantly increased contractility and cyclic AMP at a stimulation frequency of 0.5 Hz. In contrast, at 2 Hz papaverine increased only cAMP leaving the contractility unchanged. At this frequency the well-known Ca2+-antagonistic effect comes into prominence, thus masking the positive inotropic effect attributable to the inhibition of the phosphodiesterase. (3) On the right guinea-pig atrium the mediation of the positive chronotropic response to histamine by H2-receptors which is partly involved in the inotropic effect via the frequency-force relationship does not lead to a concomitant increase in cAMP. Also, in the presence of papaverine, histamine had no influence on the cAMP. However, papaverine potentiated the cardioacceleration produced by histamine. Although it is very likely that the cAMP in the sinus node rises, we were not able to detect an increase in cAMP in the whole atrial tissue. From the present results the conclusion can be drawn that the mediation of the inotropic effect due to stimulation of H2-receptors by histamine is associated with an increase of cyclic AMP, whereas that of H1-receptors is not. The view that cAMP may be the second messenger in the chronotropic action of histamine needs further elucidation by experiments on sino-atrial cells.", "contents": "H1 - and H2-receptor mediated responses to histamine on contractility and cyclic AMP of atrial and papillary muscles from guinea-pig hearts. On guinea-pig heart we investigated whether cyclic AMP serves as a messenger for H1 - and/or H2-mediated responses to histamine. (1) On papillary muscle histamine elicited positive inotropic responses which were antagonized by burimamide but not by promethazine. The stimulation of H2-receptors was not only associated with an increase in contractility but also with an increase in cAMP. As shown by the time course of effects for 10(-5) M histamine, the maximal increase in cAMP preceded the maximum in contractility. The mechanical and biochemical responses to histamine were potentiated by the phosphodiesterase inhibitor papaverine, but antagonized by burimamide. (2) On the left guinea-pig atrium containing H1-receptors the inotropic response to histamine (10(-5) M) was not accompanied by increases in cAMP at stimulation frequencies of 0.5 and 2 Hz, respectively. In addition, in the presence of papaverine (3 X 10 (-5) M) no change in the cyclic AMP level occurred after application of histamine. Papaverine by itself, however, concomitantly increased contractility and cyclic AMP at a stimulation frequency of 0.5 Hz. In contrast, at 2 Hz papaverine increased only cAMP leaving the contractility unchanged. At this frequency the well-known Ca2+-antagonistic effect comes into prominence, thus masking the positive inotropic effect attributable to the inhibition of the phosphodiesterase. (3) On the right guinea-pig atrium the mediation of the positive chronotropic response to histamine by H2-receptors which is partly involved in the inotropic effect via the frequency-force relationship does not lead to a concomitant increase in cAMP. Also, in the presence of papaverine, histamine had no influence on the cAMP. However, papaverine potentiated the cardioacceleration produced by histamine. Although it is very likely that the cAMP in the sinus node rises, we were not able to detect an increase in cAMP in the whole atrial tissue. From the present results the conclusion can be drawn that the mediation of the inotropic effect due to stimulation of H2-receptors by histamine is associated with an increase of cyclic AMP, whereas that of H1-receptors is not. The view that cAMP may be the second messenger in the chronotropic action of histamine needs further elucidation by experiments on sino-atrial cells."}
{"id": "PMID:193385", "title": "Role of phosphate, pyrophosphate, adenine nucleotides and sulfate in activating production of the superoxide radical by macrophages, and in formation of rat paw edema.", "content": "The presence of anions of phosphate (Pi), pyrophosphate (PPi), adenine nucleotides and sulfate greatly enhanced the production of superoxide radical (-O-2) by isolated guinea-pig macrophages. These anions, however, failed to enhance the production of -O-2 by the xanthine oxidase system, suggesting that they serve only as activators of -O-2 generating enzyme(s) located on the macrophage cell membrane. Many other common anions  were ineffective in the macrophage system. In the presence of concentrations of Pi, PPi, adenine-5'-triphosphate (ATP) reported to be in the synovial fluid, -O-2 was produced efficiently and was inhibited by diclofenac sodium. These anions induced rat paw edema, maintained the swelling at least up to 6 h. The edema was suppressed partially by repeated injection of superoxide dismutase (SOD). High doses of sodium chloride and nitrate failed to maintain the swelling.", "contents": "Role of phosphate, pyrophosphate, adenine nucleotides and sulfate in activating production of the superoxide radical by macrophages, and in formation of rat paw edema. The presence of anions of phosphate (Pi), pyrophosphate (PPi), adenine nucleotides and sulfate greatly enhanced the production of superoxide radical (-O-2) by isolated guinea-pig macrophages. These anions, however, failed to enhance the production of -O-2 by the xanthine oxidase system, suggesting that they serve only as activators of -O-2 generating enzyme(s) located on the macrophage cell membrane. Many other common anions  were ineffective in the macrophage system. In the presence of concentrations of Pi, PPi, adenine-5'-triphosphate (ATP) reported to be in the synovial fluid, -O-2 was produced efficiently and was inhibited by diclofenac sodium. These anions induced rat paw edema, maintained the swelling at least up to 6 h. The edema was suppressed partially by repeated injection of superoxide dismutase (SOD). High doses of sodium chloride and nitrate failed to maintain the swelling."}
{"id": "PMID:193386", "title": "A mechanism of action for non-steroidal anti-inflammatory agents in calcium pyrophosphate dihydrate (CPPD) crystal induced arthritis.", "content": "The acute inflammatory response to calcium pyrophosphate dihydrate crystals follows the meeting of neutrophils and crystals. The ensuing phagocytosis leads to the generation of a glycoprotein chemotactically active for neutrophils and to the release of lysosomal enzymes. Indomethacin and phenylbutazone, at therapeutic concentrations, impaired phagocytosis of the crystals and generation of chemotactic factor activity. Colchicine had no effect upon phagocytosis but significantly impaired the appearance of chemotactic factor activity.", "contents": "A mechanism of action for non-steroidal anti-inflammatory agents in calcium pyrophosphate dihydrate (CPPD) crystal induced arthritis. The acute inflammatory response to calcium pyrophosphate dihydrate crystals follows the meeting of neutrophils and crystals. The ensuing phagocytosis leads to the generation of a glycoprotein chemotactically active for neutrophils and to the release of lysosomal enzymes. Indomethacin and phenylbutazone, at therapeutic concentrations, impaired phagocytosis of the crystals and generation of chemotactic factor activity. Colchicine had no effect upon phagocytosis but significantly impaired the appearance of chemotactic factor activity."}
{"id": "PMID:193387", "title": "Primary adrenocortical insufficiency (Addison's disease).", "content": "In the United States the etiology of most cases of adrenal gland atrophy or destruction is unknown. Autoimmune processes may be responsible. With rare exceptions, all three zones of the adrenal cortex are destroyed and there is reduced glucocorticoid, mineralocorticoid and androgen secretion. Although the deficiency of glucocorticoid is probably the most severe threat to life, treatment is available to correct all the deficiencies. Patient education and preparedness can prevent serious complications.", "contents": "Primary adrenocortical insufficiency (Addison's disease). In the United States the etiology of most cases of adrenal gland atrophy or destruction is unknown. Autoimmune processes may be responsible. With rare exceptions, all three zones of the adrenal cortex are destroyed and there is reduced glucocorticoid, mineralocorticoid and androgen secretion. Although the deficiency of glucocorticoid is probably the most severe threat to life, treatment is available to correct all the deficiencies. Patient education and preparedness can prevent serious complications."}
{"id": "PMID:193388", "title": "Significance and treatment of nocturnal angina preceding myocardial infarction.", "content": "The presence of nocturnal angina and congestive heart failure within the month prior to admission was evaluated in the 174 patients with acute myocardial infarction. Heart size was evaluated radiographically at the time of admission. Twenty-three patients (13 per cent) experienced nocturnal angina. The incidence of nocturnal angina was significantly higher in those with anterior myocardial infarction (p less than 0.005) and subendocardial infarction (p less than 0.02) when compared with patients with inferior MI. Congestive heart failure was more common prior to admission in those with nocturnal angina (9/23) as opposed to those without (3/141) (p less than 0.001). Cardiomegaly was seen in 9/23 patients with nocturnal angina and 22/141 without (p less than 0.02). We conclude that the presence of nocturnal angina in those who develop MI increases the likelihood that the infarction will be either anterior or subendocardial rather than inferior. The association of nocturnal angina and congestive heart failure to anterior myocardial infarction is probably due to more severe and probably significant left coronary artery disease.", "contents": "Significance and treatment of nocturnal angina preceding myocardial infarction. The presence of nocturnal angina and congestive heart failure within the month prior to admission was evaluated in the 174 patients with acute myocardial infarction. Heart size was evaluated radiographically at the time of admission. Twenty-three patients (13 per cent) experienced nocturnal angina. The incidence of nocturnal angina was significantly higher in those with anterior myocardial infarction (p less than 0.005) and subendocardial infarction (p less than 0.02) when compared with patients with inferior MI. Congestive heart failure was more common prior to admission in those with nocturnal angina (9/23) as opposed to those without (3/141) (p less than 0.001). Cardiomegaly was seen in 9/23 patients with nocturnal angina and 22/141 without (p less than 0.02). We conclude that the presence of nocturnal angina in those who develop MI increases the likelihood that the infarction will be either anterior or subendocardial rather than inferior. The association of nocturnal angina and congestive heart failure to anterior myocardial infarction is probably due to more severe and probably significant left coronary artery disease."}
{"id": "PMID:193389", "title": "Morphological and histochemical organization of the flexor carpi radialis muscle in the cat.", "content": "Most studies concerning the structure and function of skeletal muscle have utilized the hind limb of the experimental animal. However, it has been shown that the number of behavioral tasks performed by the cat's forelimb is greater than that of the hind limb. In addition, the forelimb muscles exhibit a functional complexity not observed in hind-limb musculature. The purpose of this study was to investigate the distribution of fast-twitch and slow-twitch muscle fibers and muscle spindles in the flexor carpi radialis muscle (FCR) and to correlate the distributional patterns in these structures with muscle tendon architecture and muscle function. It was found that the FCR, a wrist flexor, contains 37% slow-twitch fibers and 63% fast-twitch fibers. However, the slow-twitch fibers were concentrated in the deep region located between the tendons of origin and insertion, while the fast-twitch-glycolytic fibers were concentrated more peripherally. Muscle spindles were associated with the slow-twitch region and were never found in the region containing high concentrations of fast-twitch-glycolytic fibers. Fast-twitch-oxidative-glycolytic fibers were uniformly distributed throughout the muscle. It is proposed that the association of muscle spindles with slow-twitch fibers and the differential distribution of muscle fibers into slow-twitch and fast-twitch regions might allow these regions to function independently of one another when called upon to perform complex behavioral tasks.", "contents": "Morphological and histochemical organization of the flexor carpi radialis muscle in the cat. Most studies concerning the structure and function of skeletal muscle have utilized the hind limb of the experimental animal. However, it has been shown that the number of behavioral tasks performed by the cat's forelimb is greater than that of the hind limb. In addition, the forelimb muscles exhibit a functional complexity not observed in hind-limb musculature. The purpose of this study was to investigate the distribution of fast-twitch and slow-twitch muscle fibers and muscle spindles in the flexor carpi radialis muscle (FCR) and to correlate the distributional patterns in these structures with muscle tendon architecture and muscle function. It was found that the FCR, a wrist flexor, contains 37% slow-twitch fibers and 63% fast-twitch fibers. However, the slow-twitch fibers were concentrated in the deep region located between the tendons of origin and insertion, while the fast-twitch-glycolytic fibers were concentrated more peripherally. Muscle spindles were associated with the slow-twitch region and were never found in the region containing high concentrations of fast-twitch-glycolytic fibers. Fast-twitch-oxidative-glycolytic fibers were uniformly distributed throughout the muscle. It is proposed that the association of muscle spindles with slow-twitch fibers and the differential distribution of muscle fibers into slow-twitch and fast-twitch regions might allow these regions to function independently of one another when called upon to perform complex behavioral tasks."}
{"id": "PMID:193390", "title": "Plasma triglyceride lowering by exercise despite increased food intake in patients with type IV hyperlipoproteinemia.", "content": "Exercise can lower fasting triglyceride levels (TG). This study was undertaken to determine whether the exercise-induced decrease in TG is the result of a negative caloric balance. Five subjects with primary type IV hyperlipoproteinemia were given diets comparable in composition to their usual diets. During one experimental period the subjects exercised while maintaining their usual caloric intakes. During another experimental period their caloric intake was increased to compensate for the exercise-induced increase in energy expenditure. The exercise, which consisted of 30 min of treadmill walking per day for 4 days, resulted in a progressive decrease in TG. The reduction in TG, which averaged 120 mg/100 ml, occurred regardless of whether or not the increase in caloric expenditure was compensated for by an increase in food intake. The decrease in TG was limited to the very low density lipoprotein fraction. No significant changes occurred in total plasma cholesterol concentration or in the distribution of cholesterol between the lipoprotein fractions. Fasting plasma glucagon concentration was constant for each individual and was unaffected by the exercise. The finding that exercise induces a decrease in TG despite increased food intake indicates that the TG lowering effect of exercise is not mediated by a negative caloric balance.", "contents": "Plasma triglyceride lowering by exercise despite increased food intake in patients with type IV hyperlipoproteinemia. Exercise can lower fasting triglyceride levels (TG). This study was undertaken to determine whether the exercise-induced decrease in TG is the result of a negative caloric balance. Five subjects with primary type IV hyperlipoproteinemia were given diets comparable in composition to their usual diets. During one experimental period the subjects exercised while maintaining their usual caloric intakes. During another experimental period their caloric intake was increased to compensate for the exercise-induced increase in energy expenditure. The exercise, which consisted of 30 min of treadmill walking per day for 4 days, resulted in a progressive decrease in TG. The reduction in TG, which averaged 120 mg/100 ml, occurred regardless of whether or not the increase in caloric expenditure was compensated for by an increase in food intake. The decrease in TG was limited to the very low density lipoprotein fraction. No significant changes occurred in total plasma cholesterol concentration or in the distribution of cholesterol between the lipoprotein fractions. Fasting plasma glucagon concentration was constant for each individual and was unaffected by the exercise. The finding that exercise induces a decrease in TG despite increased food intake indicates that the TG lowering effect of exercise is not mediated by a negative caloric balance."}
{"id": "PMID:193391", "title": "The \"post-heparin pattern\" in routine serum protein immunoelectrophoresis.", "content": "For some time following intravenous administration of heparin to non-fasting normal subjects, routine immunoelectrophoretic preparations show characteristic changes in serum lipoproteins. These alterations are of two types: (1) marked anodal mobility increase, the alpha-2 (beta) component locating in the alpha-1 region while the alpha-1 appears as a pre-albumin; (2) conformational alterations of the immunoprecipitin arcs comprising elongation of the alpha-2 (beta) arc, and splitting of the alpha-1 arc into two distinct entities. Familiarity with these patterns should minimize the possibility of interpretative errors with specimens from patients receiving heparin.", "contents": "The \"post-heparin pattern\" in routine serum protein immunoelectrophoresis. For some time following intravenous administration of heparin to non-fasting normal subjects, routine immunoelectrophoretic preparations show characteristic changes in serum lipoproteins. These alterations are of two types: (1) marked anodal mobility increase, the alpha-2 (beta) component locating in the alpha-1 region while the alpha-1 appears as a pre-albumin; (2) conformational alterations of the immunoprecipitin arcs comprising elongation of the alpha-2 (beta) arc, and splitting of the alpha-1 arc into two distinct entities. Familiarity with these patterns should minimize the possibility of interpretative errors with specimens from patients receiving heparin."}
{"id": "PMID:193392", "title": "Anti-\"i\" antibody and hemolytic anemia associated with spontaneous cytomegalovirus mononucleosis.", "content": "Hemolytic anemia occurred in a 23-year-old woman with spontaneous cytomegalovirus mononucleosis who had not received a blood transfusion. The patient's serum gave positive reactions in Coombs' antiglobulin test with human cord erythrocytes but did not react with adult \"O\" cells. Complement-fixation antibody titers against cytomegalovirus and levels of activity against cord erythrocytes increased as the anemia worsened and remained at high levels when recovery from the anemia occurred.", "contents": "Anti-\"i\" antibody and hemolytic anemia associated with spontaneous cytomegalovirus mononucleosis. Hemolytic anemia occurred in a 23-year-old woman with spontaneous cytomegalovirus mononucleosis who had not received a blood transfusion. The patient's serum gave positive reactions in Coombs' antiglobulin test with human cord erythrocytes but did not react with adult \"O\" cells. Complement-fixation antibody titers against cytomegalovirus and levels of activity against cord erythrocytes increased as the anemia worsened and remained at high levels when recovery from the anemia occurred."}
{"id": "PMID:193393", "title": "Bordetella parapertussis. Recent experience and a review of the literature.", "content": "During 1974, eight of 37 (22%) Bordetella organisms isolated from patients in Cincinnate were Bordetella parapertussis. This is in contrast to other experience in the United States where parapertussis has comprised less than5% of the Bordetella species isolated and suggest that B parapertussis infection may be more common in this country than generally recognized. The failure to appreciate the presence of this infection may result from the lack of cultures taken from children with mild disease and the failure todistinguish B parapertussis from B pertussis. Ccultures were obtained from family members of three of the children with B parapertussis, and  B pertussis was isolated from members of two families, including the mother and sister of a child who died of pneumonia and encephalopathy. These cases suggest that patients with severe disease associated with B parapertussis should be carefully evaluated for the possibility of dual infection caused by b pertussis.", "contents": "Bordetella parapertussis. Recent experience and a review of the literature. During 1974, eight of 37 (22%) Bordetella organisms isolated from patients in Cincinnate were Bordetella parapertussis. This is in contrast to other experience in the United States where parapertussis has comprised less than5% of the Bordetella species isolated and suggest that B parapertussis infection may be more common in this country than generally recognized. The failure to appreciate the presence of this infection may result from the lack of cultures taken from children with mild disease and the failure todistinguish B parapertussis from B pertussis. Ccultures were obtained from family members of three of the children with B parapertussis, and  B pertussis was isolated from members of two families, including the mother and sister of a child who died of pneumonia and encephalopathy. These cases suggest that patients with severe disease associated with B parapertussis should be carefully evaluated for the possibility of dual infection caused by b pertussis."}
{"id": "PMID:193394", "title": "Multicystic cerebral degeneration in neonatal herpes simplex virus encephalitis.", "content": "Typical herpetic papulovesicular skin lesions developed in an apparently normal infant at 12 days of age and were followed within 48 hours by signs and symptoms of acute encephalitis. Herpes simplex virus type 2 was cultured from the intact skin vesicles, and a fourfold increase in complement fixation titer to herpes simplex virus type 2 was found over the ensuing 24 days. The infant survived her acute illness, but was left with severe neurologic sequelae manifested as microcephaly with multicystic cerebral degeneration. The short-term and convalescent course is documented by serial, clinical, and EEG examinations, and the nature of the cerebral damage is demonstrated by computerized transaxial tomography.", "contents": "Multicystic cerebral degeneration in neonatal herpes simplex virus encephalitis. Typical herpetic papulovesicular skin lesions developed in an apparently normal infant at 12 days of age and were followed within 48 hours by signs and symptoms of acute encephalitis. Herpes simplex virus type 2 was cultured from the intact skin vesicles, and a fourfold increase in complement fixation titer to herpes simplex virus type 2 was found over the ensuing 24 days. The infant survived her acute illness, but was left with severe neurologic sequelae manifested as microcephaly with multicystic cerebral degeneration. The short-term and convalescent course is documented by serial, clinical, and EEG examinations, and the nature of the cerebral damage is demonstrated by computerized transaxial tomography."}
{"id": "PMID:193395", "title": "Cancer in chronic ulcerative colitis. Diagnostic role of segmental colonic lavage.", "content": "Saline colonic lavage in 74 patients with chronic ulcerative colitis was performed utilizing a commercially available dental irrigating unit through a polyethylene catheter in the biopsy channel of a colonoscope or through a sigmoidoscope via a lavage-aspirating double-lumen probe. Six patients were found with colonic carcinoma. Two diagnoses of malignancy were established by cytologic smears and cell block alone. Two patients had positive mucosal biopsies and cell block. One patient with a hepatic flexure carcinoma and a second patient with a malignancy proximal to the left colon stricture were missed by these techniques. Considering the established proclivity for carcinoma in these patients, it is felt that segmental lavage in areas of stricutre, grossly dostorted mucosa, or endoscopically inaccessible areas represents a valuable adjunct in the diagnosis of carcinoma in chronic ulcerative colitis.", "contents": "Cancer in chronic ulcerative colitis. Diagnostic role of segmental colonic lavage. Saline colonic lavage in 74 patients with chronic ulcerative colitis was performed utilizing a commercially available dental irrigating unit through a polyethylene catheter in the biopsy channel of a colonoscope or through a sigmoidoscope via a lavage-aspirating double-lumen probe. Six patients were found with colonic carcinoma. Two diagnoses of malignancy were established by cytologic smears and cell block alone. Two patients had positive mucosal biopsies and cell block. One patient with a hepatic flexure carcinoma and a second patient with a malignancy proximal to the left colon stricture were missed by these techniques. Considering the established proclivity for carcinoma in these patients, it is felt that segmental lavage in areas of stricutre, grossly dostorted mucosa, or endoscopically inaccessible areas represents a valuable adjunct in the diagnosis of carcinoma in chronic ulcerative colitis."}
{"id": "PMID:193397", "title": "Early acquisition of cytomegalovirus and Epstein-Barr virus antibody in several isolated Melanesian populations.", "content": "Significant differences among diverse human populations have been found in the seroepidemiology of cytomegalovirus (CMV) and Epstein-Barr virus (EBV). The present report documents a very high rate of early acquisition of antibody to CMV and EBV among three remote populations living in the Eastern Highlands of Papua New Guinea, the Solomon Islands, and the New Hebrides, respectively. These three genetically distinct populations, living in widely different ecologies and social settings, each had the same pattern of early acquisition of infection with both viruses. It is suggested that spread of CMV and EBV is determined by patterns of interpersonal contact as well as by the prevalence of virus-shedders. The large number of handlers of each infant in these studied groups appears directly related to the early acquisition of these viruses.", "contents": "Early acquisition of cytomegalovirus and Epstein-Barr virus antibody in several isolated Melanesian populations. Significant differences among diverse human populations have been found in the seroepidemiology of cytomegalovirus (CMV) and Epstein-Barr virus (EBV). The present report documents a very high rate of early acquisition of antibody to CMV and EBV among three remote populations living in the Eastern Highlands of Papua New Guinea, the Solomon Islands, and the New Hebrides, respectively. These three genetically distinct populations, living in widely different ecologies and social settings, each had the same pattern of early acquisition of infection with both viruses. It is suggested that spread of CMV and EBV is determined by patterns of interpersonal contact as well as by the prevalence of virus-shedders. The large number of handlers of each infant in these studied groups appears directly related to the early acquisition of these viruses."}
{"id": "PMID:193398", "title": "High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study.", "content": "Lipid and lipoprotein values, including fasting triglycerides and high density lipoproteins (HDL), low density lipoproteins (LDL) and total cholesterol levels, were obtained on 2,815 men and women aged 49 to 82 years chiefly between 1969 and 1971 at Framingham. In the approximately four years following the characterization of lipids, coronary heart disease developed in 79 of the 1,025 men and 63 of the 1,445 women free of coronary heart diseases. At these older ages the major potent lipid risk factor was HDL cholesterol, which had an inverse association with the incidence of coronary heart disease (p less than 0.001) in either men or women. This lipid was associated with each major manifestation of coronary heart disease. These associations were equally significant even when other lipids and other standard risk factors for coronary heart disease were taken into consideration. A weaker association with the incidence of coronary heart disease (p less than 0.05) was observed for LDL cholesterol. Triglycerides were associated with the incidence of coronary heart disease only in women and then only when the level of other lipids was not taken into account. At these ages total cholesterol was not associated with the risk of coronary heart disease.", "contents": "High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Lipid and lipoprotein values, including fasting triglycerides and high density lipoproteins (HDL), low density lipoproteins (LDL) and total cholesterol levels, were obtained on 2,815 men and women aged 49 to 82 years chiefly between 1969 and 1971 at Framingham. In the approximately four years following the characterization of lipids, coronary heart disease developed in 79 of the 1,025 men and 63 of the 1,445 women free of coronary heart diseases. At these older ages the major potent lipid risk factor was HDL cholesterol, which had an inverse association with the incidence of coronary heart disease (p less than 0.001) in either men or women. This lipid was associated with each major manifestation of coronary heart disease. These associations were equally significant even when other lipids and other standard risk factors for coronary heart disease were taken into consideration. A weaker association with the incidence of coronary heart disease (p less than 0.05) was observed for LDL cholesterol. Triglycerides were associated with the incidence of coronary heart disease only in women and then only when the level of other lipids was not taken into account. At these ages total cholesterol was not associated with the risk of coronary heart disease."}
{"id": "PMID:193400", "title": "The influence of ovarian denervation and nerve stimulation on ovarian contractions.", "content": "Two techniques were used to study the neuromuscular control of rabbit ovarian contractions. First, the ovary was denervated by stripping its artery. Spontaneous contractions were noted, as was a normal response to exogenously administered adrenergic agents. Second, the ovarian nerves were electrically stimulated in an in vitro perfused ovary system. Inhibition of ovarian contractions was noted, and the additive effects with adrenergic agents suggested a betamimetic effect of nerve stimulation in the estrous rabbit. After administration of exogenous human chorionic gonadotropin, the response was reversed. The significance of the contribution of a neuromuscular mechanism to the control of ovulation is discussed.", "contents": "The influence of ovarian denervation and nerve stimulation on ovarian contractions. Two techniques were used to study the neuromuscular control of rabbit ovarian contractions. First, the ovary was denervated by stripping its artery. Spontaneous contractions were noted, as was a normal response to exogenously administered adrenergic agents. Second, the ovarian nerves were electrically stimulated in an in vitro perfused ovary system. Inhibition of ovarian contractions was noted, and the additive effects with adrenergic agents suggested a betamimetic effect of nerve stimulation in the estrous rabbit. After administration of exogenous human chorionic gonadotropin, the response was reversed. The significance of the contribution of a neuromuscular mechanism to the control of ovulation is discussed."}
{"id": "PMID:193401", "title": "Cyclic 3',5' -adenosine monophosphate in umbilical cord and maternal plasma before and after the onset of parturition.", "content": "Significant arteriovenous differences in cord cyclic 3',5'-adenosine monophosphate (cAMP) levels and between the maternal plasma (MP) and each cord vessel (mean umbilical artery [UA] greater than umbilical vein [UV] greater than MP) was observed. cAMP levels were significantly higher in the umbilical cord vessels and maternal plasma after vaginal delivery than they were following delivery by elective cesarean section before the onset of labor. The higher mean cAMP levels observed after parturition appeared to be more pronounced in the fetoplacental unit than in the maternal compartment. A significant positive correlation in cAMP levels between the UA and UV was also observed.", "contents": "Cyclic 3',5' -adenosine monophosphate in umbilical cord and maternal plasma before and after the onset of parturition. Significant arteriovenous differences in cord cyclic 3',5'-adenosine monophosphate (cAMP) levels and between the maternal plasma (MP) and each cord vessel (mean umbilical artery [UA] greater than umbilical vein [UV] greater than MP) was observed. cAMP levels were significantly higher in the umbilical cord vessels and maternal plasma after vaginal delivery than they were following delivery by elective cesarean section before the onset of labor. The higher mean cAMP levels observed after parturition appeared to be more pronounced in the fetoplacental unit than in the maternal compartment. A significant positive correlation in cAMP levels between the UA and UV was also observed."}
{"id": "PMID:193402", "title": "A comparison of two methods for the microscopic determination of age at death.", "content": "The precision and accuracy of the Kerley and Ahlqvist-Damsten microscopic methods of age determination are compared. Both methods were applied to the same sample of 40 femoral thin sections of documented age at death. The results indicate that (1) both methods can be used with equal precision, as suggested by comparable observer errors; and (2) the Kerley method produces overall more accurate age estimates. The low previously published standard error of the Ahlqvist-Damsten method (6.71 years) apparently results from the uneven age distribution and small size (20) of their sample.", "contents": "A comparison of two methods for the microscopic determination of age at death. The precision and accuracy of the Kerley and Ahlqvist-Damsten microscopic methods of age determination are compared. Both methods were applied to the same sample of 40 femoral thin sections of documented age at death. The results indicate that (1) both methods can be used with equal precision, as suggested by comparable observer errors; and (2) the Kerley method produces overall more accurate age estimates. The low previously published standard error of the Ahlqvist-Damsten method (6.71 years) apparently results from the uneven age distribution and small size (20) of their sample."}
{"id": "PMID:193403", "title": "Cortical bone measurements in Turner's syndrome.", "content": "Cortical bone width measurements taken at midshaft on the second metacarpal were obtained from 156 hand X-rays of 80 karyotypically documented individuals with Turner's syndrome age 1 to 25 years. Total shaft width, medullary width, cortical width and percent cortical area were grouped by bone age and compared with normal female standards. Total width was significantly and increasingly below normal; medullary width was not consistently different from normal; cortical width was significantly lower from normal from age 14 onward, although it did rise at age 17 (adult bone age); percent cortical area was significantly below normal at ages 14 and 15, but was normal by adulthood. Values for percent cortical area did not indicate severe or widespread osteoporosis. Within the Turners sample cortical bone measurement were not significantly decreased in the presence of the XO sex chromosome constitution compared with other sex chromosome variants. Nor were the measurements decreased in the presence of positive metacarpal sign or a combination of typical Turner stigmata (web neck, low posterior hairline, shield chest). There was evidence that cortical width and percent cortical area increased significantly following estrogen treatment or spontaneous menarche.", "contents": "Cortical bone measurements in Turner's syndrome. Cortical bone width measurements taken at midshaft on the second metacarpal were obtained from 156 hand X-rays of 80 karyotypically documented individuals with Turner's syndrome age 1 to 25 years. Total shaft width, medullary width, cortical width and percent cortical area were grouped by bone age and compared with normal female standards. Total width was significantly and increasingly below normal; medullary width was not consistently different from normal; cortical width was significantly lower from normal from age 14 onward, although it did rise at age 17 (adult bone age); percent cortical area was significantly below normal at ages 14 and 15, but was normal by adulthood. Values for percent cortical area did not indicate severe or widespread osteoporosis. Within the Turners sample cortical bone measurement were not significantly decreased in the presence of the XO sex chromosome constitution compared with other sex chromosome variants. Nor were the measurements decreased in the presence of positive metacarpal sign or a combination of typical Turner stigmata (web neck, low posterior hairline, shield chest). There was evidence that cortical width and percent cortical area increased significantly following estrogen treatment or spontaneous menarche."}
{"id": "PMID:193404", "title": "Radiological anthropometry of the hand in Turner's syndrome.", "content": "Metacarpal-phalangeal (M-P) lengths, metacarpal sign, and carpal angle were studied using 142 pairs of hand X-rays from 81 individuals with Turner's syndrome age 6 to 25 years. Left M-P lengths, grouped by bone age, were compared with normal female standards and Z-score pattern profiles calculated for each bone age. Differences between Turners and normals in most M-P lengths increased with age, particularly after puberty. Calculation of inter-individual and intra-individual variability yielded good evidence for a M-P pattern profile typical of Turner's syndrome, with increasing growth deficiency from distal to proximal and lateral to medial. The incidence of positive metacarpal sign was 33.8%, with no significant difference between XO and non-XO Turners. It did not appear that M4 ceased growth prematurely, suggesting that short M4 is not the result of early epiphyseal fusion. Carpal angle, reported to be abnormally decreased in Turners, was not found to differ from normal. There was no difference between right and left sides or between XO and non-XO Turners, but carpal angle did decrease significantly with both decreasing ulnar deviation in positioning of the hand and increasing age. In the latter respect Turners differ from normals who show an increase in carpal angle with age.", "contents": "Radiological anthropometry of the hand in Turner's syndrome. Metacarpal-phalangeal (M-P) lengths, metacarpal sign, and carpal angle were studied using 142 pairs of hand X-rays from 81 individuals with Turner's syndrome age 6 to 25 years. Left M-P lengths, grouped by bone age, were compared with normal female standards and Z-score pattern profiles calculated for each bone age. Differences between Turners and normals in most M-P lengths increased with age, particularly after puberty. Calculation of inter-individual and intra-individual variability yielded good evidence for a M-P pattern profile typical of Turner's syndrome, with increasing growth deficiency from distal to proximal and lateral to medial. The incidence of positive metacarpal sign was 33.8%, with no significant difference between XO and non-XO Turners. It did not appear that M4 ceased growth prematurely, suggesting that short M4 is not the result of early epiphyseal fusion. Carpal angle, reported to be abnormally decreased in Turners, was not found to differ from normal. There was no difference between right and left sides or between XO and non-XO Turners, but carpal angle did decrease significantly with both decreasing ulnar deviation in positioning of the hand and increasing age. In the latter respect Turners differ from normals who show an increase in carpal angle with age."}
{"id": "PMID:193405", "title": "Response of mitochondria of different types of skeletal muscle to thyrotoxicosis.", "content": "To determine the effect of long-term thyrotoxicosis on muscle mitochondria, we measured representative mitochondrial enzymes from three different types of skeletal muscle (fast-twitch red and fast-twitch white from the quadriceps, and slow-twitch red from the soleus) in rats given 3 mg L-thyroxine and 1 mg triiodo-L-thyronine per kilogram of diet for 12 wk. Marker enzymes of the electron transport chain and citric acid cycle (cytochrome oxidase, cytochrome c, and citrate synthase) increase approximately twofold in soleus muscle in response to this treatment. The fast-twitch muscles exhibit no more than 44% increases in these enzymes in response to the same treatment. Relative to initial concentration, 3-hydroxybutyrate dehydrogenase increased to the same extent in fast-twitch red muscle as it did in the soleus (70%). Mitochondrial alpha-glycerophosphate dehydrogenase increased 76% in red quadriceps and 170% in soleus, but did not change in white muscle in the thyrotoxic rats. This differential sensitivity of the three types of muscle provides a tool for studying the mechanisms underlying the action of thyroid hormones on muscle mitochondria.", "contents": "Response of mitochondria of different types of skeletal muscle to thyrotoxicosis. To determine the effect of long-term thyrotoxicosis on muscle mitochondria, we measured representative mitochondrial enzymes from three different types of skeletal muscle (fast-twitch red and fast-twitch white from the quadriceps, and slow-twitch red from the soleus) in rats given 3 mg L-thyroxine and 1 mg triiodo-L-thyronine per kilogram of diet for 12 wk. Marker enzymes of the electron transport chain and citric acid cycle (cytochrome oxidase, cytochrome c, and citrate synthase) increase approximately twofold in soleus muscle in response to this treatment. The fast-twitch muscles exhibit no more than 44% increases in these enzymes in response to the same treatment. Relative to initial concentration, 3-hydroxybutyrate dehydrogenase increased to the same extent in fast-twitch red muscle as it did in the soleus (70%). Mitochondrial alpha-glycerophosphate dehydrogenase increased 76% in red quadriceps and 170% in soleus, but did not change in white muscle in the thyrotoxic rats. This differential sensitivity of the three types of muscle provides a tool for studying the mechanisms underlying the action of thyroid hormones on muscle mitochondria."}
{"id": "PMID:193406", "title": "Thyroid hormone control of Na+-K+-ATPase and K+-dependent phosphatase in rat heart.", "content": "To assess the possible role of the Na+ pump in mediating physiological responses to thyroid hormone in the rat myocardium, we examined the effects of L-3,5,3'-triiodothyronine (T3) on the activities of the closely associated enzymes, Na+-K+-dependent adenosine triphosphatase (Na-K-ATPase) and K+-dependent p-nitrophenyl phosphatase (K-dep-pNPPase). In hypothyroid rats, administration of T3 (50 microng/100 g body wt) resulted in significant increases (greater than 50%) in Na-K-ATPase and K-dep-pNPPase activities in both crude homogenates and microsomal fractions of the rat ventricle. Significant effects on Na-K-ATPase activity were also attained with low doses (1 microng/100 g body wt) of T3. A method was developed for assaying K-dep-pNPPase activity in cardiac slices. With this technique, enhancement in K-dep-pNPPase activity of 89.2% was found in ventricle slices after treatment of hypothyroid rats with T3 (50 microng/100 g body wt), implying that augmentation of the capacity of the Na+ pump is achieved in vivo. The potent analogue, L-3,5-diiodo-3' isopropyl thyronine (isopropyl T2) had the same effects on cardiac growth and Na-K-ATPase as T3, in hypothyroid rats. In contrast, the relatively inactive isomer, L-3,3',5'-triiodothyronine (reverse T3) had no significant effect on the heart weight-to-body weight ratio or on ventricular Na-K-ATPase activity.", "contents": "Thyroid hormone control of Na+-K+-ATPase and K+-dependent phosphatase in rat heart. To assess the possible role of the Na+ pump in mediating physiological responses to thyroid hormone in the rat myocardium, we examined the effects of L-3,5,3'-triiodothyronine (T3) on the activities of the closely associated enzymes, Na+-K+-dependent adenosine triphosphatase (Na-K-ATPase) and K+-dependent p-nitrophenyl phosphatase (K-dep-pNPPase). In hypothyroid rats, administration of T3 (50 microng/100 g body wt) resulted in significant increases (greater than 50%) in Na-K-ATPase and K-dep-pNPPase activities in both crude homogenates and microsomal fractions of the rat ventricle. Significant effects on Na-K-ATPase activity were also attained with low doses (1 microng/100 g body wt) of T3. A method was developed for assaying K-dep-pNPPase activity in cardiac slices. With this technique, enhancement in K-dep-pNPPase activity of 89.2% was found in ventricle slices after treatment of hypothyroid rats with T3 (50 microng/100 g body wt), implying that augmentation of the capacity of the Na+ pump is achieved in vivo. The potent analogue, L-3,5-diiodo-3' isopropyl thyronine (isopropyl T2) had the same effects on cardiac growth and Na-K-ATPase as T3, in hypothyroid rats. In contrast, the relatively inactive isomer, L-3,3',5'-triiodothyronine (reverse T3) had no significant effect on the heart weight-to-body weight ratio or on ventricular Na-K-ATPase activity."}
{"id": "PMID:193407", "title": "Evidence for interference of 25 (OH) vitamin D3 with phosphaturic action of calcitonin.", "content": "The present study evaluated the effect of 25(OH)vitamin D3[25(OH)vit D3] on the phosphaturic action of calcitonin in anesthetized parathyroidectomized rats. In group 1, calcitonin was given intravenously over six clearance periods. In group 2, after three periods of calcitonin given intravenously, 25(OH)vit D3 was added and given together with calcitonin for three additional periods. During calcitonin infusion, Cp/CIn 0.18 +/- 0.02 (mean +/- SE) in group 1 was not different from the corresponding Cp/CIn 0.18 +/- 0.03 in group 2; but when 25(OH)vit D3 was added, Cp/CIn 0.12 +/- 0.01 in group 2 was lower (P less than 0.001) than the corresponding Cp/CIn 0.26 +/- 0.02 in group 1. With intravenous calcitonin the urinary excretion of cycle AMP (UcAMP) 97 +/- 29 in group 1 did not differ from the corresponding UcAMP 86 +/- 27 pmol/min in group 2, but when 25(OH)vit D3 was added UcAMP 41 +/- 12 in group 2 was lower (P less than 0.001) than the corresponding UcAMP 131 +/- 14 pmol/min in group 1. This study demonstrated that 25(OH)vit D3 blocks the phosphaturic action of calcitonin. The associated fall in Uctamp suggests that25 (OV)vit D3 acts possibly by inhibiting the calcitonin-induced activation of adenylate cyclase in the kidney. However, other alternative mechanisms of action have not been excluded.", "contents": "Evidence for interference of 25 (OH) vitamin D3 with phosphaturic action of calcitonin. The present study evaluated the effect of 25(OH)vitamin D3[25(OH)vit D3] on the phosphaturic action of calcitonin in anesthetized parathyroidectomized rats. In group 1, calcitonin was given intravenously over six clearance periods. In group 2, after three periods of calcitonin given intravenously, 25(OH)vit D3 was added and given together with calcitonin for three additional periods. During calcitonin infusion, Cp/CIn 0.18 +/- 0.02 (mean +/- SE) in group 1 was not different from the corresponding Cp/CIn 0.18 +/- 0.03 in group 2; but when 25(OH)vit D3 was added, Cp/CIn 0.12 +/- 0.01 in group 2 was lower (P less than 0.001) than the corresponding Cp/CIn 0.26 +/- 0.02 in group 1. With intravenous calcitonin the urinary excretion of cycle AMP (UcAMP) 97 +/- 29 in group 1 did not differ from the corresponding UcAMP 86 +/- 27 pmol/min in group 2, but when 25(OH)vit D3 was added UcAMP 41 +/- 12 in group 2 was lower (P less than 0.001) than the corresponding UcAMP 131 +/- 14 pmol/min in group 1. This study demonstrated that 25(OH)vit D3 blocks the phosphaturic action of calcitonin. The associated fall in Uctamp suggests that25 (OV)vit D3 acts possibly by inhibiting the calcitonin-induced activation of adenylate cyclase in the kidney. However, other alternative mechanisms of action have not been excluded."}
{"id": "PMID:193408", "title": "Dependence of tonin activity in rat submaxillary gland on growth hormone and testosterone.", "content": "Tonin, an enzyme present in rat submaxillary gland, converts angiotensin I to angiotensin II and is able to form angiotensin II directly from renin substrates. This enzyme was previously shown to be different from renin, tissue isorenins, and angiotensin I converting enzyme. The specific activity of tonin in rat submaxillary gland increases with the age of the animal and is much higher in male than in female rats; this sex difference is apparent from 60 to 70 days of age. There is a sharp drop of tonin activity in hypophysectomized animals, whereas adrenalectomy, thyroidectomy, and gonadectomy have have little effect. The marked increase in tonin activity was observed in animals bearing MtT-F4 transplantable tumors known to produce ACTH, prolactin, and growth hormone. Tonin specific activity in hypophysectomized male rats is restored to control levels by combined treatment with growth hormone and testosterone. Prolactin alone or in combination with testosterone, as well as transplanted pituitaries, has no effect in hypophysectomized animals. There is a significant specific binding of 125I-labeled growth hormone to isolated membranes of rat submaxillary gland.", "contents": "Dependence of tonin activity in rat submaxillary gland on growth hormone and testosterone. Tonin, an enzyme present in rat submaxillary gland, converts angiotensin I to angiotensin II and is able to form angiotensin II directly from renin substrates. This enzyme was previously shown to be different from renin, tissue isorenins, and angiotensin I converting enzyme. The specific activity of tonin in rat submaxillary gland increases with the age of the animal and is much higher in male than in female rats; this sex difference is apparent from 60 to 70 days of age. There is a sharp drop of tonin activity in hypophysectomized animals, whereas adrenalectomy, thyroidectomy, and gonadectomy have have little effect. The marked increase in tonin activity was observed in animals bearing MtT-F4 transplantable tumors known to produce ACTH, prolactin, and growth hormone. Tonin specific activity in hypophysectomized male rats is restored to control levels by combined treatment with growth hormone and testosterone. Prolactin alone or in combination with testosterone, as well as transplanted pituitaries, has no effect in hypophysectomized animals. There is a significant specific binding of 125I-labeled growth hormone to isolated membranes of rat submaxillary gland."}
{"id": "PMID:193409", "title": "Depriving rats of REM sleep: the identification of a methodological problem.", "content": "Several studies that used Jouvet's platform-in-the-water technique to deprive rats of REM sleep are reviewed. It is observed that a consistent feature of the design of these studies was to ignore the ratio between the size of the animal and the diameter of the platform when the REM deprivation was manipulated. Some contradictory studies are considered, and it is shown that the discrepant outcomes in the literature could be the result of inattention to that ratio.", "contents": "Depriving rats of REM sleep: the identification of a methodological problem. Several studies that used Jouvet's platform-in-the-water technique to deprive rats of REM sleep are reviewed. It is observed that a consistent feature of the design of these studies was to ignore the ratio between the size of the animal and the diameter of the platform when the REM deprivation was manipulated. Some contradictory studies are considered, and it is shown that the discrepant outcomes in the literature could be the result of inattention to that ratio."}
{"id": "PMID:193410", "title": "Subselective angiography in localizing insulinomas of the pancreas.", "content": "Preoperative angiography was performed on 10 patients who had insulin-producing islet cell adenomas. Eight of the 10 islet cell tumors were localized. Seven of the eight adenomas were demonstrated only on subselective injections into the small intrapancreatic arteries, and one was demonstrated by a selective injection into a large artery. Failure to localize two islet cell adenomas was probably caused by the inability to subselect the small intrapancreatic arteries supplying the tumor. One tumor was seen only with subtraction techniques, which were used in all cases. Localization was not related to vascularity, size of tumor, or location within the pancreas. Vasoconstrictive pharmacoangiography was not helpful; magnification was helpful but not essential. The most important factor in localizing islet cell tumors is demonstrating the complete pancreatic blood supply with subselective injections into the small intrapancreatic arteries supplying the tumor (inferior and superior pancreaticoduodenal and dorsal arteries).", "contents": "Subselective angiography in localizing insulinomas of the pancreas. Preoperative angiography was performed on 10 patients who had insulin-producing islet cell adenomas. Eight of the 10 islet cell tumors were localized. Seven of the eight adenomas were demonstrated only on subselective injections into the small intrapancreatic arteries, and one was demonstrated by a selective injection into a large artery. Failure to localize two islet cell adenomas was probably caused by the inability to subselect the small intrapancreatic arteries supplying the tumor. One tumor was seen only with subtraction techniques, which were used in all cases. Localization was not related to vascularity, size of tumor, or location within the pancreas. Vasoconstrictive pharmacoangiography was not helpful; magnification was helpful but not essential. The most important factor in localizing islet cell tumors is demonstrating the complete pancreatic blood supply with subselective injections into the small intrapancreatic arteries supplying the tumor (inferior and superior pancreaticoduodenal and dorsal arteries)."}
{"id": "PMID:193411", "title": "Antimicrobial systems of the surgical wound. I. A comparison of oxidative metabolism and microbicidal capacity of phagocytes from wounds and from peripheral blood.", "content": "Oxygen consumption glucose oxidation via the hexose monophosphate shunt, and superoxide production by resting and stimulated leukocytes derived from rabbit blood and from experimental rabbit wounds five to seventeen days old were measured and compared. In vitro killing of staphylococci by blood and wound leukocytes was also measured. In all of these studies there were no significant functional differences between blood and wound cells. The data presented suggest that under the same in vitro conditions, blood and wound leukocytes are functionally equivalent, that tissue mobilization does not cause alteration of wound leukocytes, and that aging of the wound does not impair the microbicidal capacity of wound leukocytes.", "contents": "Antimicrobial systems of the surgical wound. I. A comparison of oxidative metabolism and microbicidal capacity of phagocytes from wounds and from peripheral blood. Oxygen consumption glucose oxidation via the hexose monophosphate shunt, and superoxide production by resting and stimulated leukocytes derived from rabbit blood and from experimental rabbit wounds five to seventeen days old were measured and compared. In vitro killing of staphylococci by blood and wound leukocytes was also measured. In all of these studies there were no significant functional differences between blood and wound cells. The data presented suggest that under the same in vitro conditions, blood and wound leukocytes are functionally equivalent, that tissue mobilization does not cause alteration of wound leukocytes, and that aging of the wound does not impair the microbicidal capacity of wound leukocytes."}
{"id": "PMID:193413", "title": "Cytochemical localiztion of nucleoside diphosphatase and thiamine pyrophosphatase activities in the rabbit corneal endothelium.", "content": "Localization of NDPase and TPPase activities in the rabbit corneal endothelium was investigated by cytochemical methods. After incubation at both pH 7.0 and 8.0, the NDPase activity was detected in cisternae of ER, nuclear envelope, and Golgi saccules, while the TPPase activity was demonstrated only in Golgi saccules. The reaction products of both enzymes were decreased when incubated at pH 8.0. The NDPase activity was inhibited by uranyl nitrate but not by sodium fluoride, while the TPPase was inhibited by fluoride but not by uranium.", "contents": "Cytochemical localiztion of nucleoside diphosphatase and thiamine pyrophosphatase activities in the rabbit corneal endothelium. Localization of NDPase and TPPase activities in the rabbit corneal endothelium was investigated by cytochemical methods. After incubation at both pH 7.0 and 8.0, the NDPase activity was detected in cisternae of ER, nuclear envelope, and Golgi saccules, while the TPPase activity was demonstrated only in Golgi saccules. The reaction products of both enzymes were decreased when incubated at pH 8.0. The NDPase activity was inhibited by uranyl nitrate but not by sodium fluoride, while the TPPase was inhibited by fluoride but not by uranium."}
{"id": "PMID:193418", "title": "[The origin of histological changes in amebiasis].", "content": "On microscopic examination of histological specimens from an autopsy case with severe amoebiasis, extensive ulcerative-necrotic lesions in the colon were found associated with an amoebic peritonitis and severe degenerative lesions of the ganglion-cells of the plexus myentericus induced by Entamoeba histolytica. There was also an infiltration of a mesenteric lymphnode by amoebae carried by the lymph through the vasa afferentiae lymphaticae. In the liver several granulomas (amoebic granulomas) and numerous small necrotic areas, surrounded by a dense leucocytic infiltration, were observed. The origin of the lesions in the colon could be attributed to the motility of the amoebae and the secretion of lytic substances (ferments) by the amoebae, whereas the lesions in the liver (amoebic granulomas and necrotic areas) must be considered as the residues of the destroyed amoebae which were brought by the circulation into the liver parenchyma. These lesions are similar to those seen in experimentally produced amoebiasis.", "contents": "[The origin of histological changes in amebiasis]. On microscopic examination of histological specimens from an autopsy case with severe amoebiasis, extensive ulcerative-necrotic lesions in the colon were found associated with an amoebic peritonitis and severe degenerative lesions of the ganglion-cells of the plexus myentericus induced by Entamoeba histolytica. There was also an infiltration of a mesenteric lymphnode by amoebae carried by the lymph through the vasa afferentiae lymphaticae. In the liver several granulomas (amoebic granulomas) and numerous small necrotic areas, surrounded by a dense leucocytic infiltration, were observed. The origin of the lesions in the colon could be attributed to the motility of the amoebae and the secretion of lytic substances (ferments) by the amoebae, whereas the lesions in the liver (amoebic granulomas and necrotic areas) must be considered as the residues of the destroyed amoebae which were brought by the circulation into the liver parenchyma. These lesions are similar to those seen in experimentally produced amoebiasis."}
{"id": "PMID:193419", "title": "Decreased granulocyte response to isoproterenol in asthma during upper respiratory infections.", "content": "Isoproterenol inhibits zymosan-stimulated release of lysosomal enzymes from granulocytes. Using this as an in vitro cell model to study beta-adrenergic response, granulocyte reaction to isoproterenol was examined in asthma. There was a significantly decreased response to isoproterenol (10(-7) to 10(+-5) M) in patients with mild asthma who had not taken bronchodilators for 2 weeks before study and also in patients with severe asthma requiring bronchodilators and corticosteroids. During respiratory infections that provoked an attack of asthma, the granulocyte response to isoproterenol was further decreased. The change in granulocyte response to isoproterenol may reflect a similar change in beta-adrenergic tone of the airways and provide one explanation for asthma during colds.", "contents": "Decreased granulocyte response to isoproterenol in asthma during upper respiratory infections. Isoproterenol inhibits zymosan-stimulated release of lysosomal enzymes from granulocytes. Using this as an in vitro cell model to study beta-adrenergic response, granulocyte reaction to isoproterenol was examined in asthma. There was a significantly decreased response to isoproterenol (10(-7) to 10(+-5) M) in patients with mild asthma who had not taken bronchodilators for 2 weeks before study and also in patients with severe asthma requiring bronchodilators and corticosteroids. During respiratory infections that provoked an attack of asthma, the granulocyte response to isoproterenol was further decreased. The change in granulocyte response to isoproterenol may reflect a similar change in beta-adrenergic tone of the airways and provide one explanation for asthma during colds."}
{"id": "PMID:193415", "title": "The activity of some nucleolytic enzymes in semen and in the secretion of the male reproductive tract.", "content": "The activity of 5'-nucleotidase (EC 1.3.5), cyclic nucleotide phosphodiesterase (EC 2.1.4.17), non-specific phosphodiesterase (EC 3.1.4.1) and ribonuclease (EC 1.7.7.16)has been investigated in the seminal plasma of whole semen and in the secretions of the seminal vesicle, prostate and epididymis of the bull, boar, ram, stallion, jackass, rabbit and man. Bull seminal plasma showed the highest activity for 5'-nucleotidase, cyclic nucleotide phosphodiesterase and ribonuclease; in contrast, stallion and jackass semen were very poor in these enzymes. Ram, rabbit and boar seminal plasma showed intermediate levels for all enzymes studied. In the bull and ram, nucleolytic enzymes were found to be secreted by the seminal vesicles but in the boar, rabbit and stallion they originate mostly from the epididymis. In human seminal plasma all of the enzymes studied exhibited activity but the levels were generally lower than those recorded for the other species.", "contents": "The activity of some nucleolytic enzymes in semen and in the secretion of the male reproductive tract. The activity of 5'-nucleotidase (EC 1.3.5), cyclic nucleotide phosphodiesterase (EC 2.1.4.17), non-specific phosphodiesterase (EC 3.1.4.1) and ribonuclease (EC 1.7.7.16)has been investigated in the seminal plasma of whole semen and in the secretions of the seminal vesicle, prostate and epididymis of the bull, boar, ram, stallion, jackass, rabbit and man. Bull seminal plasma showed the highest activity for 5'-nucleotidase, cyclic nucleotide phosphodiesterase and ribonuclease; in contrast, stallion and jackass semen were very poor in these enzymes. Ram, rabbit and boar seminal plasma showed intermediate levels for all enzymes studied. In the bull and ram, nucleolytic enzymes were found to be secreted by the seminal vesicles but in the boar, rabbit and stallion they originate mostly from the epididymis. In human seminal plasma all of the enzymes studied exhibited activity but the levels were generally lower than those recorded for the other species."}
{"id": "PMID:193420", "title": "[Etiology of acute respiratory infection in hospitalized children (author's transl)].", "content": "Incidence of respiratory tract infection represents 23% of the total number of admissions between 1-24 months of age, during a period of 18 months. The diagnosis were: bronchiolities, 143 cases; bronchopneumonia, 134 cases; tracheobronchitis, 50 cases; laryngitis, four cases, and bacterial pneumonia, 61 cases. Monthly incidence was maximal in December of each year. From the total group, 144 cases were included in the present study to determine etiology of the infection. In 19% of the cases a serological diagnosis was posible. The adenovirus group was the most frequently found, followed by mycoplasma pneumoniae, parainfluenza 2, RS virus and M. parotiditis. RS virus was associated with a clinical picture of bronchopneumonia, mycoplasma pneumoniae with one of bronchiolitis and adenovirus was indistinctly associated with features either bronchopneumonia or bronchiolitis. In two cases it was detected a mixed infection by two virus: influenza 2 and mycoplasma pneumoniae. In four cases a bacterial surinfection was demonstrated: in two cases with coagulase-positive staphilococus and other two with klebsiella pneumoniae.", "contents": "[Etiology of acute respiratory infection in hospitalized children (author's transl)]. Incidence of respiratory tract infection represents 23% of the total number of admissions between 1-24 months of age, during a period of 18 months. The diagnosis were: bronchiolities, 143 cases; bronchopneumonia, 134 cases; tracheobronchitis, 50 cases; laryngitis, four cases, and bacterial pneumonia, 61 cases. Monthly incidence was maximal in December of each year. From the total group, 144 cases were included in the present study to determine etiology of the infection. In 19% of the cases a serological diagnosis was posible. The adenovirus group was the most frequently found, followed by mycoplasma pneumoniae, parainfluenza 2, RS virus and M. parotiditis. RS virus was associated with a clinical picture of bronchopneumonia, mycoplasma pneumoniae with one of bronchiolitis and adenovirus was indistinctly associated with features either bronchopneumonia or bronchiolitis. In two cases it was detected a mixed infection by two virus: influenza 2 and mycoplasma pneumoniae. In four cases a bacterial surinfection was demonstrated: in two cases with coagulase-positive staphilococus and other two with klebsiella pneumoniae."}
{"id": "PMID:193416", "title": "Gonadotrophin levels in male rats following impairment of Leydig cell function by ethylene dimethanesulphonate.", "content": "The effects of the antispermatogenic compound, ethylene dimethanesulphonate on anterior pituitary and serum FSH, LH and prolactin levels in male rats were investigated. A rapid and sustained rise in serum LH, reaching castrate levels, indictated a normal pituitary response to androgen deprivation. Whilst no change in prolactin was observed, serum FSH showed a biphasic increase which is discussed in relation to the spermatogenic process.", "contents": "Gonadotrophin levels in male rats following impairment of Leydig cell function by ethylene dimethanesulphonate. The effects of the antispermatogenic compound, ethylene dimethanesulphonate on anterior pituitary and serum FSH, LH and prolactin levels in male rats were investigated. A rapid and sustained rise in serum LH, reaching castrate levels, indictated a normal pituitary response to androgen deprivation. Whilst no change in prolactin was observed, serum FSH showed a biphasic increase which is discussed in relation to the spermatogenic process."}
{"id": "PMID:193423", "title": "Subcellular localization of enzymes.", "content": "Localization of enzyme activity at the subcellular level requires techniques that have been essentially developed for the conventional light microscopic histochemistry and modified to fulfull the requirements of high resolution. Such procedures are manipulated in a certain sequence that starts with a short period of fixation, capture of the enzyme activity, postosmication and then dehydration followed by embedding of the specimen in a suitable plastic medium. References for the study of some selected enzymes pertinent to the hepatocytic organelles and their response under varied conditions are given as an example of the various procedures applied. Absence of glucose-6-phosphatase activity is currently used as a marker for the detection of early formation of preneoplastic cells in the liver of experimental animals treated with hepatocarcinogens and other agents.", "contents": "Subcellular localization of enzymes. Localization of enzyme activity at the subcellular level requires techniques that have been essentially developed for the conventional light microscopic histochemistry and modified to fulfull the requirements of high resolution. Such procedures are manipulated in a certain sequence that starts with a short period of fixation, capture of the enzyme activity, postosmication and then dehydration followed by embedding of the specimen in a suitable plastic medium. References for the study of some selected enzymes pertinent to the hepatocytic organelles and their response under varied conditions are given as an example of the various procedures applied. Absence of glucose-6-phosphatase activity is currently used as a marker for the detection of early formation of preneoplastic cells in the liver of experimental animals treated with hepatocarcinogens and other agents."}
{"id": "PMID:193421", "title": "[Massive tumours of the parotid. A description of 12 cases (author's transl)].", "content": "A number of useful conclusions can be drawn from this research involving twelve personal cases. In the southern half of Madagascar, malignant tumours of the parotid are much more frequent than mixed tumours. This appears to be true whatever the age or sex of the patient or the clinical characteristics encountered. The absence of facial paralysis and adenopathy should never be considered to invalidate this theory. Mixed tumours exist but in about the same proportion as other tumours (cysts or vascular tumours) which are to be found here. When faced with any large latero-cervical tumour with no O.R.L. entrypoint or homo- or contro-lateral adenopathy, where there is no arteriography or extemporaneous biopsy available, the parotid should always spring to mind, and when surgery is carried out, the cervico-facial branch of the VIIth nerve at the lower pole or at the lower external face of the tumour should first be singled out.", "contents": "[Massive tumours of the parotid. A description of 12 cases (author's transl)]. A number of useful conclusions can be drawn from this research involving twelve personal cases. In the southern half of Madagascar, malignant tumours of the parotid are much more frequent than mixed tumours. This appears to be true whatever the age or sex of the patient or the clinical characteristics encountered. The absence of facial paralysis and adenopathy should never be considered to invalidate this theory. Mixed tumours exist but in about the same proportion as other tumours (cysts or vascular tumours) which are to be found here. When faced with any large latero-cervical tumour with no O.R.L. entrypoint or homo- or contro-lateral adenopathy, where there is no arteriography or extemporaneous biopsy available, the parotid should always spring to mind, and when surgery is carried out, the cervico-facial branch of the VIIth nerve at the lower pole or at the lower external face of the tumour should first be singled out."}
{"id": "PMID:193429", "title": "Cytomegalovirus (CMV) in the compromised host(s).", "content": "Cytomegalovirus infection in compromised hosts occurs most frequently as asymptomatic shedding of a reactivated virus. Reactivation occurs when cellular immunity is compromised owing to either immune-deficiency disease or iatrogenic intervention. When intervention is modest, most antibody-positive patients do not shed virus (19); when the group is treated with a higher mean dose of cytotoxic agents, almost all antibody-positive patients shed virus (6). In the instance where the chemotherapeutic program includes massive doses of these agents, as in heart or marrow transplantation, or when dysfunction of all cellular activity is extreme, as in the case of severe combined immune deficiency and far-advanced neoplasia, dissemination of infection with multiple-organ involvement ensues (17, 20-22). Primary infection may occur in some patients with neoplasia or in marrow-transplant recipients from either blood transfusions or from marrow, although data are insufficient to be certain (22). It has been conclusively shown, however, that seronegative renal-allograft recipients usually develop primary infection when they acquire a kidney from a seropositive donor. Clinical illness related to virus infection in the first few months after transplantation occurs in almost all patients with primary infection and seldom in those with reactivation infection (6, 25, 26). Three very intriguing observations have been made that should suggest avenues for future research: (a) Since illness occurs more closely related to development of antibody than it does to onset of virus shedding, this suggests that host response plays an important role in the disease that is obviously caused by a virus; a definition of the mechanism of this interaction could lead to an understanding of host-induced disease processes in man; (b) Graft-versus-host disease in marrow transplantation; and (c) allograft rejection in renal-graft recipients correlate with development of CMV infection (16, 22, 24, 26). Taken together, these observations are consistent with the hypothesis that virus antigens interrelate with most antigens in such a way as to lead to immune response to both antigens. Exploration of this clinical observation could lead to a greater understanding of the function of the HL-A system in man.", "contents": "Cytomegalovirus (CMV) in the compromised host(s). Cytomegalovirus infection in compromised hosts occurs most frequently as asymptomatic shedding of a reactivated virus. Reactivation occurs when cellular immunity is compromised owing to either immune-deficiency disease or iatrogenic intervention. When intervention is modest, most antibody-positive patients do not shed virus (19); when the group is treated with a higher mean dose of cytotoxic agents, almost all antibody-positive patients shed virus (6). In the instance where the chemotherapeutic program includes massive doses of these agents, as in heart or marrow transplantation, or when dysfunction of all cellular activity is extreme, as in the case of severe combined immune deficiency and far-advanced neoplasia, dissemination of infection with multiple-organ involvement ensues (17, 20-22). Primary infection may occur in some patients with neoplasia or in marrow-transplant recipients from either blood transfusions or from marrow, although data are insufficient to be certain (22). It has been conclusively shown, however, that seronegative renal-allograft recipients usually develop primary infection when they acquire a kidney from a seropositive donor. Clinical illness related to virus infection in the first few months after transplantation occurs in almost all patients with primary infection and seldom in those with reactivation infection (6, 25, 26). Three very intriguing observations have been made that should suggest avenues for future research: (a) Since illness occurs more closely related to development of antibody than it does to onset of virus shedding, this suggests that host response plays an important role in the disease that is obviously caused by a virus; a definition of the mechanism of this interaction could lead to an understanding of host-induced disease processes in man; (b) Graft-versus-host disease in marrow transplantation; and (c) allograft rejection in renal-graft recipients correlate with development of CMV infection (16, 22, 24, 26). Taken together, these observations are consistent with the hypothesis that virus antigens interrelate with most antigens in such a way as to lead to immune response to both antigens. Exploration of this clinical observation could lead to a greater understanding of the function of the HL-A system in man."}
{"id": "PMID:193424", "title": "Enzymes in amniotic fluid.", "content": "The determination of enzyme levels in cell-free amniotic fluid has proven useful in assessing fetal maturity and fetal well being, and is being utilized for the prenatal diagnosis of genetic disorders. The activities of amylase, alpha-galactosidase, phosphatidic acid phosphohydrolase, lysozyme and heat-stable alkaline phosphatase in amniotic fluid increase with gestational age and have an established relationship to fetal maturity. The ratio of amniotic fluid diamine oxidase activity to maternal serum activity (amniotic DAO/serum DAO) may be used as an indicator of the degree of rhesus isoimmunization after 28 weeks gestation. Creatine phosphokinase in amniotic fluid is elevated in cases of in utero fetal death and is of diagnostic significance. The prenatal diagnosis of Tay-Sachs disease, Sandhoff's disease, fucosidosis, GM1-gangliosidosis and I-cell disease have been made from the analysis of appropriate enzymes in cell-free amniotic fluid.", "contents": "Enzymes in amniotic fluid. The determination of enzyme levels in cell-free amniotic fluid has proven useful in assessing fetal maturity and fetal well being, and is being utilized for the prenatal diagnosis of genetic disorders. The activities of amylase, alpha-galactosidase, phosphatidic acid phosphohydrolase, lysozyme and heat-stable alkaline phosphatase in amniotic fluid increase with gestational age and have an established relationship to fetal maturity. The ratio of amniotic fluid diamine oxidase activity to maternal serum activity (amniotic DAO/serum DAO) may be used as an indicator of the degree of rhesus isoimmunization after 28 weeks gestation. Creatine phosphokinase in amniotic fluid is elevated in cases of in utero fetal death and is of diagnostic significance. The prenatal diagnosis of Tay-Sachs disease, Sandhoff's disease, fucosidosis, GM1-gangliosidosis and I-cell disease have been made from the analysis of appropriate enzymes in cell-free amniotic fluid."}
{"id": "PMID:193430", "title": "Diagnosis of hyperparathyroidism.", "content": "States of hypersecretion of PTH may occur primarily, or in response to other physiologic abnormalities. Primary hyperparathyroidism must be considered in the differential diagnosis of hypercalcemia, nephrolithiasis, metabolic bone disease, and pancreatitis and peptic-ulcer disease. The clinical manifestations of this disease have become more subtle with improved detection. The serum calcium level is almost always elevated, and when it it accompanied by relatively high serum PTH levels or increased urinary cAMP excretion, the diagnosis is usually secure. Findings of hypophosphatemia, decreased renal tubular reabsorption of phosphorus, hypercalciuria, and characteristic roentgenographic changes support the diagnosis of hyperparathyroidism, but are not prerequisites for that diagnosis. Most cases will come to operation, and experienced intraoperative assessment is necessary for the correct distinction between multiglandular disease and that involving only a single gland. We expect that a clearer understanding of the histopathologic features of these diseases, and improvement in the methods for measurement of PTH will be the main areas of advancement in the diagnosis of hyperparathyroidism in the next few years.", "contents": "Diagnosis of hyperparathyroidism. States of hypersecretion of PTH may occur primarily, or in response to other physiologic abnormalities. Primary hyperparathyroidism must be considered in the differential diagnosis of hypercalcemia, nephrolithiasis, metabolic bone disease, and pancreatitis and peptic-ulcer disease. The clinical manifestations of this disease have become more subtle with improved detection. The serum calcium level is almost always elevated, and when it it accompanied by relatively high serum PTH levels or increased urinary cAMP excretion, the diagnosis is usually secure. Findings of hypophosphatemia, decreased renal tubular reabsorption of phosphorus, hypercalciuria, and characteristic roentgenographic changes support the diagnosis of hyperparathyroidism, but are not prerequisites for that diagnosis. Most cases will come to operation, and experienced intraoperative assessment is necessary for the correct distinction between multiglandular disease and that involving only a single gland. We expect that a clearer understanding of the histopathologic features of these diseases, and improvement in the methods for measurement of PTH will be the main areas of advancement in the diagnosis of hyperparathyroidism in the next few years."}
{"id": "PMID:193433", "title": "Pathophysiology of psoriasis.", "content": "Psoriasis is a disease characterized by benign but unrestricted epithelial growth. The molecular pathophysiology of this unregulated growth has been discussed. A better understanding of the role of the cell surface, cyclic nucleotides, arachidonic acid-prostaglandin metabolism, and polyamines in psoriasis may clarify our understanding of this disease and produce clues pertinent to a general understanding of growth regulation.", "contents": "Pathophysiology of psoriasis. Psoriasis is a disease characterized by benign but unrestricted epithelial growth. The molecular pathophysiology of this unregulated growth has been discussed. A better understanding of the role of the cell surface, cyclic nucleotides, arachidonic acid-prostaglandin metabolism, and polyamines in psoriasis may clarify our understanding of this disease and produce clues pertinent to a general understanding of growth regulation."}
{"id": "PMID:193434", "title": "Surgical adjuvant chemotherapy.", "content": "The evidence that the principles of surgical adjuvant chemotherapy developed in experimental animal systems also apply to a variety of neoplastic diseases in man has been clearly demonstrated. Micrometastatic disease can be eradicated with effective chemotherapy in several diseases. Prolongation of disease-free interval, if not cure, is now possible in diseases in which curative surgery alone or in combination with radiotherapy does not achieve these goals. The previously fatal childhood solid tumors--Wilms', Ewings' sarcoma, embryonal rhabdomyosarcoma--are curable in a high percentage of patients appropriately treated with combinations of surgery, radiotherapy, and chemotherapy. The prolongation of the disease-free interval in osteogenic sarcoma has permitted consideration of entirely new surgical approaches for this tumor in which radical amputation has traditionally been employed. The spectacular results achieved in the treatment of Stage II breast cancer may potentially save hundreds of thousands of lives in the coming decade. Clinically recognizable metastatic disease is rarely curable by any currently available treatment modality. The prolongation of disease-free intervals and production of cures when surgical adjuvant chemotherapy is employed may be partly explained by relatively more circulation, and thus drug delivery to each tumor cell, more favorable cellular kinetics, and a healthier and more immunocompetent host who is better able to withstand drug effects on normal tissues, and to participate in tumor destruction. Cures of certain patients with neoplastic diseases using surgical adjuvant chemotherapy has increased the incentive to learn more about new and old drugs and their effective use alone and in combination. Chemotherapy, in appropriate combinations with surgery, radiotherapy, and immunotherapy, may well be more efficacious in many clinical situations than the traditional use of single-modality treatment. The data presented in this paper relate solid evidence that the possibility of cure in a variety of neoplastic diseases is real.", "contents": "Surgical adjuvant chemotherapy. The evidence that the principles of surgical adjuvant chemotherapy developed in experimental animal systems also apply to a variety of neoplastic diseases in man has been clearly demonstrated. Micrometastatic disease can be eradicated with effective chemotherapy in several diseases. Prolongation of disease-free interval, if not cure, is now possible in diseases in which curative surgery alone or in combination with radiotherapy does not achieve these goals. The previously fatal childhood solid tumors--Wilms', Ewings' sarcoma, embryonal rhabdomyosarcoma--are curable in a high percentage of patients appropriately treated with combinations of surgery, radiotherapy, and chemotherapy. The prolongation of the disease-free interval in osteogenic sarcoma has permitted consideration of entirely new surgical approaches for this tumor in which radical amputation has traditionally been employed. The spectacular results achieved in the treatment of Stage II breast cancer may potentially save hundreds of thousands of lives in the coming decade. Clinically recognizable metastatic disease is rarely curable by any currently available treatment modality. The prolongation of disease-free intervals and production of cures when surgical adjuvant chemotherapy is employed may be partly explained by relatively more circulation, and thus drug delivery to each tumor cell, more favorable cellular kinetics, and a healthier and more immunocompetent host who is better able to withstand drug effects on normal tissues, and to participate in tumor destruction. Cures of certain patients with neoplastic diseases using surgical adjuvant chemotherapy has increased the incentive to learn more about new and old drugs and their effective use alone and in combination. Chemotherapy, in appropriate combinations with surgery, radiotherapy, and immunotherapy, may well be more efficacious in many clinical situations than the traditional use of single-modality treatment. The data presented in this paper relate solid evidence that the possibility of cure in a variety of neoplastic diseases is real."}
{"id": "PMID:193437", "title": "Cytochemical and biochemical studies of yeasts after in vitro exposure to miconazole.", "content": "Yeast cells exposed to different doses of the antimycotic agent miconazole revealed important cytochemical changes in the topographic distribution of the phosphatases. A strong effect was observed on the behavior of oxidative and peroxidative enzymes. Decreased cytochrome c oxidase and peroxidase activity and increased catalase activity were seen after treatment with a fungistatic dose of miconazole, whereas a complete disappearance of these enzymes was observed after treatment with a minimal fungicidal dose of miconazole. This was in complete agreement with the quantitative biochemical data. A hypothesis is advanced concerning the possible involvement of peroxidase and catalase in the mechanism of action of this drug.", "contents": "Cytochemical and biochemical studies of yeasts after in vitro exposure to miconazole. Yeast cells exposed to different doses of the antimycotic agent miconazole revealed important cytochemical changes in the topographic distribution of the phosphatases. A strong effect was observed on the behavior of oxidative and peroxidative enzymes. Decreased cytochrome c oxidase and peroxidase activity and increased catalase activity were seen after treatment with a fungistatic dose of miconazole, whereas a complete disappearance of these enzymes was observed after treatment with a minimal fungicidal dose of miconazole. This was in complete agreement with the quantitative biochemical data. A hypothesis is advanced concerning the possible involvement of peroxidase and catalase in the mechanism of action of this drug."}
{"id": "PMID:193438", "title": "Inhibition of cellular and viral protein synthesis by 3-methyleneoxindole.", "content": "The effect of 3-methyleneoxindole (MO) on mengovirus and L-cell protein synthesis was investigated. MO was found to inhibit mengovirus multiplication and the incorporation of radioactive amino acids into both viral and cellular proteins. These results suggest that the antiviral effect of this compound is not specific but rather stems from its inhibition of the cellular translational machinery upon which mengovirus depends. We have also found that MO inhibits natural messenger ribonucleic acid (mengovirus and globin messenger ribonucleic acid) translation in cell-free extracts from Ehrlich ascites tumor cells but has no significant effect on polyuridylic acid translation. Additional data which suggest that MO inhibits protein synthesis at the level of initiation are shown.", "contents": "Inhibition of cellular and viral protein synthesis by 3-methyleneoxindole. The effect of 3-methyleneoxindole (MO) on mengovirus and L-cell protein synthesis was investigated. MO was found to inhibit mengovirus multiplication and the incorporation of radioactive amino acids into both viral and cellular proteins. These results suggest that the antiviral effect of this compound is not specific but rather stems from its inhibition of the cellular translational machinery upon which mengovirus depends. We have also found that MO inhibits natural messenger ribonucleic acid (mengovirus and globin messenger ribonucleic acid) translation in cell-free extracts from Ehrlich ascites tumor cells but has no significant effect on polyuridylic acid translation. Additional data which suggest that MO inhibits protein synthesis at the level of initiation are shown."}
{"id": "PMID:193439", "title": "Comparison of the effects of mecillinam and 6-aminopenicillanic acid on Proteus mirabilis, Escherichia coli, and Staphylococcus aureus.", "content": "Single strains of Proteus mirabilis, Escherichia coli, and Staphylococcus aureus were grown on filter membranes placed on agar containing concentration series of mecillinam (FL 1060), 6-aminopenicillanic acid (6-APA), or ampicillin. P. mirabilis and E. coli were also exposed to combinations of mecillinam or 6-APA with ampicillin. Colony-forming units were counted, and cells were examined by interference phase-contrast and transmission electron microscopy. Mecillinam and 6-APA were very effective in reducing the viability of the two gram-negative species, but they were less effective against S. aureus. Combinations of mecillinam and 6-APA with ampicillin acted synergistically against the gram-negative bacilli. When the antibiotics were presented consecutively, their effects on viability were usually no greater than the effects of the individual antibiotics acting alone. When P. mirabilis and E. coli were exposed to mecillinam alone or in combination with ampicillin, the cells became rounded. 6-APA alone or in combination with ampicillin produced elongated polymorphic cells in these species. The most unusual morphological effects were ultrastructural. Mecillinam and, to a lesser extent, 6-APA produced inward growth of numerous pairs of trilamellar membranous structures within the cells. It is possible that these membranes represent the growth initiation of aberrant cross walls. Both mecillinam and 6-APA produced multiple, thick cross walls in S. aureus.", "contents": "Comparison of the effects of mecillinam and 6-aminopenicillanic acid on Proteus mirabilis, Escherichia coli, and Staphylococcus aureus. Single strains of Proteus mirabilis, Escherichia coli, and Staphylococcus aureus were grown on filter membranes placed on agar containing concentration series of mecillinam (FL 1060), 6-aminopenicillanic acid (6-APA), or ampicillin. P. mirabilis and E. coli were also exposed to combinations of mecillinam or 6-APA with ampicillin. Colony-forming units were counted, and cells were examined by interference phase-contrast and transmission electron microscopy. Mecillinam and 6-APA were very effective in reducing the viability of the two gram-negative species, but they were less effective against S. aureus. Combinations of mecillinam and 6-APA with ampicillin acted synergistically against the gram-negative bacilli. When the antibiotics were presented consecutively, their effects on viability were usually no greater than the effects of the individual antibiotics acting alone. When P. mirabilis and E. coli were exposed to mecillinam alone or in combination with ampicillin, the cells became rounded. 6-APA alone or in combination with ampicillin produced elongated polymorphic cells in these species. The most unusual morphological effects were ultrastructural. Mecillinam and, to a lesser extent, 6-APA produced inward growth of numerous pairs of trilamellar membranous structures within the cells. It is possible that these membranes represent the growth initiation of aberrant cross walls. Both mecillinam and 6-APA produced multiple, thick cross walls in S. aureus."}
{"id": "PMID:193440", "title": "Susceptibility of clinical isolates of cytomegalovirus to human interferon.", "content": "Human cell culture-derived interferon was shown to inhibit human cytomegalovirus in vitro. A prototype strain, Davis, and six clinical isolates of cytomegalovirus were tested. All six isolates showed uniform susceptibility to interferon, exceeding that of the Davis strain by two- to fourfold. The latter virus was found to be 32 to 4 times less susceptible than the sensitive indicator, vesicular stomatitis virus. However, the laboratory finding of susceptibility to an antiviral material may not relate to its clinical effectiveness.", "contents": "Susceptibility of clinical isolates of cytomegalovirus to human interferon. Human cell culture-derived interferon was shown to inhibit human cytomegalovirus in vitro. A prototype strain, Davis, and six clinical isolates of cytomegalovirus were tested. All six isolates showed uniform susceptibility to interferon, exceeding that of the Davis strain by two- to fourfold. The latter virus was found to be 32 to 4 times less susceptible than the sensitive indicator, vesicular stomatitis virus. However, the laboratory finding of susceptibility to an antiviral material may not relate to its clinical effectiveness."}
{"id": "PMID:193441", "title": "Susceptibility of Clostridium perfringens isolated from human infections to twenty antibiotics.", "content": "The proper choice of antibiotic for Clostridium perfringens infections in patients allergic to penicillin is not clear; the usual recommendations and recent in vitro studies disagree. We tested the susceptibility of 57 strains of C. perfringens to eight penicillins, seven cephalosporins, two tetracyclines, clindamycin, chloramphenicol, and rifampin by the agar dilution method. All strains were inhibited by (per milliliter) 4 mug or less of any of the penicillins, chloramphenicol, or clindamycin and 8 mug or less of any of the cephalosporins tested. Penicillin G and amoxicillin inhibited all strains at 0.12 mug or less per ml. Only 54% of the strains were inhibited by 1 mug of tetracycline per ml. Penicillin G remains the drug of first choice for infections with C. perfringens; it need not be added to a regimen containing a penicillinase-resistant penicillin given parenterally in high doses. The cephalosporins should be considered as alternative drugs for penicillin-allergic patients. Clindamycin and chloramphenicol are also effective. Tetracyclines cannot be depended upon in clostridial infections without in vitro testing, which is impracticable for initial empirical therapy.", "contents": "Susceptibility of Clostridium perfringens isolated from human infections to twenty antibiotics. The proper choice of antibiotic for Clostridium perfringens infections in patients allergic to penicillin is not clear; the usual recommendations and recent in vitro studies disagree. We tested the susceptibility of 57 strains of C. perfringens to eight penicillins, seven cephalosporins, two tetracyclines, clindamycin, chloramphenicol, and rifampin by the agar dilution method. All strains were inhibited by (per milliliter) 4 mug or less of any of the penicillins, chloramphenicol, or clindamycin and 8 mug or less of any of the cephalosporins tested. Penicillin G and amoxicillin inhibited all strains at 0.12 mug or less per ml. Only 54% of the strains were inhibited by 1 mug of tetracycline per ml. Penicillin G remains the drug of first choice for infections with C. perfringens; it need not be added to a regimen containing a penicillinase-resistant penicillin given parenterally in high doses. The cephalosporins should be considered as alternative drugs for penicillin-allergic patients. Clindamycin and chloramphenicol are also effective. Tetracyclines cannot be depended upon in clostridial infections without in vitro testing, which is impracticable for initial empirical therapy."}
{"id": "PMID:193445", "title": "(3H)-isoproterenol binding to subcellular fractions of mouse parotid: relationship to cyclic nucleotide formation and the stimulation of DNA synthesis.", "content": "(3H) Isoproterenol binding to subcellular fractions of mouse parotid: Relationship to cyclic nucleotide formation and the stimulation of DNA synthesis. (Uni\u00f3n the (3H) Isoproterenol a fracciones subcelulares de par\u00f3tida de rat\u00f3n y su relac\u00f3n con la formac\u00f3n de nucle\u00f3tidos c\u00edclicos y la estimulaci\u00f3n de la s\u00edntesis de DNA). Arch. Biol. Med. Exper. 10: 105-114, 1976. Tritiated isoproterenol binds to all subcellular fractions of mouse parotid but 70% of the binding is to the nuclear fraction. Binding to other mouse tissues was less than to the parotid. The patterns of binding did not correlate with the distribution of adenylate cyclase, guanylate cyclase or catechol-O-methyl transferase among the fractions or tissues nor with the extent of response in stimulation of DNA synthesis among the tissues. Inhibition of (3H) Isoproterenol binding to parotid fractions by catecholamine analogs was studied. There was no correlation between their ability to inhibit binding and the ability of the analogs themselves to raise cyclic AMP levels or stimulate DNA synthesis.", "contents": "(3H)-isoproterenol binding to subcellular fractions of mouse parotid: relationship to cyclic nucleotide formation and the stimulation of DNA synthesis. (3H) Isoproterenol binding to subcellular fractions of mouse parotid: Relationship to cyclic nucleotide formation and the stimulation of DNA synthesis. (Uni\u00f3n the (3H) Isoproterenol a fracciones subcelulares de par\u00f3tida de rat\u00f3n y su relac\u00f3n con la formac\u00f3n de nucle\u00f3tidos c\u00edclicos y la estimulaci\u00f3n de la s\u00edntesis de DNA). Arch. Biol. Med. Exper. 10: 105-114, 1976. Tritiated isoproterenol binds to all subcellular fractions of mouse parotid but 70% of the binding is to the nuclear fraction. Binding to other mouse tissues was less than to the parotid. The patterns of binding did not correlate with the distribution of adenylate cyclase, guanylate cyclase or catechol-O-methyl transferase among the fractions or tissues nor with the extent of response in stimulation of DNA synthesis among the tissues. Inhibition of (3H) Isoproterenol binding to parotid fractions by catecholamine analogs was studied. There was no correlation between their ability to inhibit binding and the ability of the analogs themselves to raise cyclic AMP levels or stimulate DNA synthesis."}
{"id": "PMID:193446", "title": "Salt extraction of chromatin from normal diploid and SV-40 transformed human fibroblasts.", "content": "Regulation of cell proliferation is a complex but exceedingly interesting form of gene expression. Overwhelming evidence in the past ten years has shown that the flow of cells through the cell cycle, and the regulation of cell population  density, are under the control of the eukaryotic genome. Changes in the function and structure of chromatin have been reported when G0 cells are stimulated to proliferate and when continuously dividing cells move through the different phases of the cell cycle from G1 to S, G2 and mitosis. The changes occurring in the structure and function of chromatin seem to be related to changes occurring in the chromosomal proteins, especially non-histone chromosomal proteins and chromatin-bound protein kinases. Studies are now in progress to isolate the genes, with their respective proteins, that regulate the different steps of the cell cycle.", "contents": "Salt extraction of chromatin from normal diploid and SV-40 transformed human fibroblasts. Regulation of cell proliferation is a complex but exceedingly interesting form of gene expression. Overwhelming evidence in the past ten years has shown that the flow of cells through the cell cycle, and the regulation of cell population  density, are under the control of the eukaryotic genome. Changes in the function and structure of chromatin have been reported when G0 cells are stimulated to proliferate and when continuously dividing cells move through the different phases of the cell cycle from G1 to S, G2 and mitosis. The changes occurring in the structure and function of chromatin seem to be related to changes occurring in the chromosomal proteins, especially non-histone chromosomal proteins and chromatin-bound protein kinases. Studies are now in progress to isolate the genes, with their respective proteins, that regulate the different steps of the cell cycle."}
{"id": "PMID:193448", "title": "Immunological disorders and malignancies in five young brothers.", "content": "Five brothers of from 6 to 18 years of age experienced immunological or neoplastic disorders during an 8-year interval. 2 boys succumbed to glioblastoma multiforme, another to metastatic carcinoma, and the 2 surviving brothers had a histiocytic lymphoma and idiopathic thrombocytopenia purpura, respectively. The mother of the boys was healthy, but her twin sister died in utero of birth defects. We suggest that an intrinsic cellular defect inherited from their mother rendered the boys vulnerable to oncogenesis.", "contents": "Immunological disorders and malignancies in five young brothers. Five brothers of from 6 to 18 years of age experienced immunological or neoplastic disorders during an 8-year interval. 2 boys succumbed to glioblastoma multiforme, another to metastatic carcinoma, and the 2 surviving brothers had a histiocytic lymphoma and idiopathic thrombocytopenia purpura, respectively. The mother of the boys was healthy, but her twin sister died in utero of birth defects. We suggest that an intrinsic cellular defect inherited from their mother rendered the boys vulnerable to oncogenesis."}
{"id": "PMID:193449", "title": "[On the biologic phenomenon of epidermotropism (author's transl)].", "content": "The biologic phenomenon of epidermotropism is mirrored in the dynamic equilibrium between different cell types within the epidermis. In various pathological conditions, this balance may be upset, or foreign epithelial, neuroectodermal and mesenchymal tissue may selectively infiltrate epidermal or other epithelial structures. The importance of the concept of epidermal symbiosis in these conditions and resulting similarities in the clinical picture and biologic behavior are pointed out.", "contents": "[On the biologic phenomenon of epidermotropism (author's transl)]. The biologic phenomenon of epidermotropism is mirrored in the dynamic equilibrium between different cell types within the epidermis. In various pathological conditions, this balance may be upset, or foreign epithelial, neuroectodermal and mesenchymal tissue may selectively infiltrate epidermal or other epithelial structures. The importance of the concept of epidermal symbiosis in these conditions and resulting similarities in the clinical picture and biologic behavior are pointed out."}
{"id": "PMID:193450", "title": "The impact of long term estrogen support after hysterectomy. A report of 1016 cases.", "content": "1016 Women were placed on estrogen support following hysterectomy and have been followed for a total of 14,318 patient/years. Support was principally conjugated estrogen with the customary dose 1.5 mg/day. The follow-up studies in this group of women shows a marked drop in deaths from all causes over those which might have been expected. This improvement in mortality is principally the result of diminished number of deaths from heart attack and from cancer. Those causes of death which would not be expected to be related to hormonal therapy show the anticipated number of mortalities. There is also a marked improvement in the clinical evidence of osteoporosis. In this group there is an increase in the number of breast cancers over those which might have been expected, but there is a lower mortality from breast cancer than the anticipated mortality. The general impact of long-term estrogen therapy following hysterectomy is favorable over those figures for the expected incidence of cancer and heart disease.", "contents": "The impact of long term estrogen support after hysterectomy. A report of 1016 cases. 1016 Women were placed on estrogen support following hysterectomy and have been followed for a total of 14,318 patient/years. Support was principally conjugated estrogen with the customary dose 1.5 mg/day. The follow-up studies in this group of women shows a marked drop in deaths from all causes over those which might have been expected. This improvement in mortality is principally the result of diminished number of deaths from heart attack and from cancer. Those causes of death which would not be expected to be related to hormonal therapy show the anticipated number of mortalities. There is also a marked improvement in the clinical evidence of osteoporosis. In this group there is an increase in the number of breast cancers over those which might have been expected, but there is a lower mortality from breast cancer than the anticipated mortality. The general impact of long-term estrogen therapy following hysterectomy is favorable over those figures for the expected incidence of cancer and heart disease."}
{"id": "PMID:193451", "title": "Clinical significance of circulating C-peptide in diabetes mellitus and hypoglycemic disorders.", "content": "Proinsulin is converted to insulin and C-peptide in the pancreatic in the pancreatic beta cells: the latter two peptides are secreted in equimolar concentrations. Thus, measurements of serum C-peptide provide a means of assessing pancreatic beta cell function in addition to that of insulin. This technique has proved particularly useful in insulin treated diabetic patients in whom the development of circulating insulin antibodies interferes with the radioimmunoassay of the hormone. The C-peptide assay has also been used to facilitate the diagnosis of various hypoglycemic conditions, including islet cell tumors and factitious injection of insulin. The extraction of C-peptide in the urine reflects average serum values over a period of time and urine C-peptide measurements are especially useful in children or individuals in whom repeated blood sampling is difficult.", "contents": "Clinical significance of circulating C-peptide in diabetes mellitus and hypoglycemic disorders. Proinsulin is converted to insulin and C-peptide in the pancreatic in the pancreatic beta cells: the latter two peptides are secreted in equimolar concentrations. Thus, measurements of serum C-peptide provide a means of assessing pancreatic beta cell function in addition to that of insulin. This technique has proved particularly useful in insulin treated diabetic patients in whom the development of circulating insulin antibodies interferes with the radioimmunoassay of the hormone. The C-peptide assay has also been used to facilitate the diagnosis of various hypoglycemic conditions, including islet cell tumors and factitious injection of insulin. The extraction of C-peptide in the urine reflects average serum values over a period of time and urine C-peptide measurements are especially useful in children or individuals in whom repeated blood sampling is difficult."}
{"id": "PMID:193452", "title": "Single units activities in ventral posterior and posterior group thalamic nuclei during nociceptive and non nociceptive stimulations in the cat.", "content": "The purpose of this study was to define, in hyperventilated and unanesthetized cats, the role of the posterior thalamic nuclei in pain mechanisms. Unit activities of these structures were compared to those of the ventro-posterior nucleus during non-noxious (touch, brushing) and noxious stimulations (pinches and intra-arterial injections of bradykinin into the limbs). 135 cells with somatic inputs and clear peripheral excitatory receptive field were studied. The cells driven by noxious stimulations were located in the posterior group nuclei as anatomically defined by Rinvik. These units, preferentially excited from contralateral receptive fields, were localized in POm, POl, suprageniculate nuclei, the magnocellular division of the medial geniculate body (Mgmc) and the ventral part of the lateral posterior nucleus. At this level two groups of units were found: those driven only by noxious stimulations and those driven by both noxious and non-noxious stimulations. On contrast, cells recorded at the levels of the VPm and VPl were not activated by noxious stimuli. These results emphasize the role of the posterior thalamic nuclei in pain processing.", "contents": "Single units activities in ventral posterior and posterior group thalamic nuclei during nociceptive and non nociceptive stimulations in the cat. The purpose of this study was to define, in hyperventilated and unanesthetized cats, the role of the posterior thalamic nuclei in pain mechanisms. Unit activities of these structures were compared to those of the ventro-posterior nucleus during non-noxious (touch, brushing) and noxious stimulations (pinches and intra-arterial injections of bradykinin into the limbs). 135 cells with somatic inputs and clear peripheral excitatory receptive field were studied. The cells driven by noxious stimulations were located in the posterior group nuclei as anatomically defined by Rinvik. These units, preferentially excited from contralateral receptive fields, were localized in POm, POl, suprageniculate nuclei, the magnocellular division of the medial geniculate body (Mgmc) and the ventral part of the lateral posterior nucleus. At this level two groups of units were found: those driven only by noxious stimulations and those driven by both noxious and non-noxious stimulations. On contrast, cells recorded at the levels of the VPm and VPl were not activated by noxious stimuli. These results emphasize the role of the posterior thalamic nuclei in pain processing."}
{"id": "PMID:193456", "title": "Adenoid cystic carcinoma of the breast. Light and electron microscopy and a brief review of the literature.", "content": "The case of two patients with adenoid cystic carcinoma of the breast are reported. In case 1, the predominant pattern was that of a solid, basaloid, cylindromatous tumor, whereas case 2 showed the typical adenoid cystic appearance. Results of electron microscopical study confirmed that many of the cystic spaces seen by light microscopy were extracellular compartments enclosed by tumor cells. Many of the tumor cells contained densely packed fibrils, which support the myoepithelial origin of these tumors. Approximately 92 well-documented reports of this lesion are briefly reviewed.", "contents": "Adenoid cystic carcinoma of the breast. Light and electron microscopy and a brief review of the literature. The case of two patients with adenoid cystic carcinoma of the breast are reported. In case 1, the predominant pattern was that of a solid, basaloid, cylindromatous tumor, whereas case 2 showed the typical adenoid cystic appearance. Results of electron microscopical study confirmed that many of the cystic spaces seen by light microscopy were extracellular compartments enclosed by tumor cells. Many of the tumor cells contained densely packed fibrils, which support the myoepithelial origin of these tumors. Approximately 92 well-documented reports of this lesion are briefly reviewed."}
{"id": "PMID:193457", "title": "Pseudoadenoid cystic carcinoma of the breast.", "content": "An example of a cribriform intraductal carcinoma that closely resembled adenoid cystic carcinoma is described. The true nature of the tumor was revealed by electron microscopy and the case is used to demonstrate that the diagnosis of this tumor cannot be safely made by routine histologic techniques alone. Review of conflicting views othe value of mucin histochemistry expressed in the literature suggest that ultrastructural examination is a useful alternative tool in the differentiation of adenoid cystic carcinoma of the breast from cribriform intraductal carcinoma.", "contents": "Pseudoadenoid cystic carcinoma of the breast. An example of a cribriform intraductal carcinoma that closely resembled adenoid cystic carcinoma is described. The true nature of the tumor was revealed by electron microscopy and the case is used to demonstrate that the diagnosis of this tumor cannot be safely made by routine histologic techniques alone. Review of conflicting views othe value of mucin histochemistry expressed in the literature suggest that ultrastructural examination is a useful alternative tool in the differentiation of adenoid cystic carcinoma of the breast from cribriform intraductal carcinoma."}
{"id": "PMID:193458", "title": "Tubular carcinoma of the breast. Clinical, histological, and ultrastructural observations.", "content": "Tubular carcinoma is a neoplasm with good prognosis of features that warrant its differentiation from other mammary carcinomas and from sclerosing adenosis. Cases of nine primary unilateral neoplasms are presented and ultrastructural observations in three discussed. The mean diameter was 1.2 cm and the mean patient age was 48.7 years. None of the patients died and only one of six had residual tumor in the mastectomy specimens. Three patients had an excisional biopsy, one followed by radiation. All biopsy specimens showed infiltrating angular tubules with single-lining epithelium, minimal anaplasia, rare mitosis, and scant or absent myoepithelium. The tumor cells related to each other by desmosomes, cytoplasmic interlocking processes, and tight junctions. Myoepithelial cells were rare. Since tubular carcinomas are distinct variety of ductal epithelial neoplasms of the breast, and are well differentiated with low malignant biological behavior, a less radical approach may be the treatment of choice.", "contents": "Tubular carcinoma of the breast. Clinical, histological, and ultrastructural observations. Tubular carcinoma is a neoplasm with good prognosis of features that warrant its differentiation from other mammary carcinomas and from sclerosing adenosis. Cases of nine primary unilateral neoplasms are presented and ultrastructural observations in three discussed. The mean diameter was 1.2 cm and the mean patient age was 48.7 years. None of the patients died and only one of six had residual tumor in the mastectomy specimens. Three patients had an excisional biopsy, one followed by radiation. All biopsy specimens showed infiltrating angular tubules with single-lining epithelium, minimal anaplasia, rare mitosis, and scant or absent myoepithelium. The tumor cells related to each other by desmosomes, cytoplasmic interlocking processes, and tight junctions. Myoepithelial cells were rare. Since tubular carcinomas are distinct variety of ductal epithelial neoplasms of the breast, and are well differentiated with low malignant biological behavior, a less radical approach may be the treatment of choice."}
{"id": "PMID:193459", "title": "Paget disease of the male breast.", "content": "Twenty-two fully documented cases of Paget disease of the male breast are reviewed, and an additional patient is reported. The most common initial symptom was ulceration and excoriation, while a breast mass was palpable in the majority of patients. Nipple changes were surprisingly rare, in contrast to the female. The prognosis of the disease in the male appears to be worse than in the female, with the Paget carcinoma carrying a worse prognosis than the \"ordinary\" male breast cancer. The subareolar location and the meager volume of tissue interposed between the tumor and chest wall may be an important factor in this regard. Nipple changes or symptoms (ulceration, discharge, enlargement) are mroe apt to be due to cancer in the male than in the female. Therefore, prompt diagnosis is mandatory.", "contents": "Paget disease of the male breast. Twenty-two fully documented cases of Paget disease of the male breast are reviewed, and an additional patient is reported. The most common initial symptom was ulceration and excoriation, while a breast mass was palpable in the majority of patients. Nipple changes were surprisingly rare, in contrast to the female. The prognosis of the disease in the male appears to be worse than in the female, with the Paget carcinoma carrying a worse prognosis than the \"ordinary\" male breast cancer. The subareolar location and the meager volume of tissue interposed between the tumor and chest wall may be an important factor in this regard. Nipple changes or symptoms (ulceration, discharge, enlargement) are mroe apt to be due to cancer in the male than in the female. Therefore, prompt diagnosis is mandatory."}
{"id": "PMID:193460", "title": "Progesterone receptor in cystosarcoma phyllodes.", "content": "A specific receptor for progesterone has been found in a cystosarcoma phyllodes, as determined by charcoal adsorption and sucrose gradient analysis. Similar assays for estrogen receptors were negative. The tumor consisted almost entirely of stroma that contained the progesterone receptors. The epidemiology and natural history of cystosarcoma do not strongly support the hypothesis that it is controlled by female sex hormones, but the presence of the progesterone receptors suggests that some cystosarcomas are hormonally regulated, and thus may be responsive to therapeutic hormonal manipulation.", "contents": "Progesterone receptor in cystosarcoma phyllodes. A specific receptor for progesterone has been found in a cystosarcoma phyllodes, as determined by charcoal adsorption and sucrose gradient analysis. Similar assays for estrogen receptors were negative. The tumor consisted almost entirely of stroma that contained the progesterone receptors. The epidemiology and natural history of cystosarcoma do not strongly support the hypothesis that it is controlled by female sex hormones, but the presence of the progesterone receptors suggests that some cystosarcomas are hormonally regulated, and thus may be responsive to therapeutic hormonal manipulation."}
{"id": "PMID:193461", "title": "Surgical management of hepatic vein occlusion by tumor: Budd-Chiari syndrome.", "content": "We report new operative approaches to the treatment of hepatic vein occlusion due to malignant tumors in the liver and their results in four patients. Two patients had hepatoma, one had metastatic melanoma, and one had metastatic leiomyosarcoma. All of them had abdominal pain, abdominal distention secondary to ascites, and massive hepatomegaly. The right lobe and medial segment of the left lobe of the liver were involved in three patients, and the involvement was diffuse throughout the liver in one. Hepatic veins were occluded completely in one patient, and two of three veins were occluded in the others. Two patients were treated by hepatic resection and removal of tumor thrombus from the hepatic vein under isolation-perfusion technique. They lived 18 and six months, respectively, without recurrence of Budd-Chiari syndrome. Tumors in the other patients were diffuse and could not be resected. The hepatic artery was ligated and chemotherapy was given postoperatively. Ascites and abdominal pain disappeared completely in one, who survived 17 months. The other patient had significant palliation and lived nine months.", "contents": "Surgical management of hepatic vein occlusion by tumor: Budd-Chiari syndrome. We report new operative approaches to the treatment of hepatic vein occlusion due to malignant tumors in the liver and their results in four patients. Two patients had hepatoma, one had metastatic melanoma, and one had metastatic leiomyosarcoma. All of them had abdominal pain, abdominal distention secondary to ascites, and massive hepatomegaly. The right lobe and medial segment of the left lobe of the liver were involved in three patients, and the involvement was diffuse throughout the liver in one. Hepatic veins were occluded completely in one patient, and two of three veins were occluded in the others. Two patients were treated by hepatic resection and removal of tumor thrombus from the hepatic vein under isolation-perfusion technique. They lived 18 and six months, respectively, without recurrence of Budd-Chiari syndrome. Tumors in the other patients were diffuse and could not be resected. The hepatic artery was ligated and chemotherapy was given postoperatively. Ascites and abdominal pain disappeared completely in one, who survived 17 months. The other patient had significant palliation and lived nine months."}
{"id": "PMID:193462", "title": "IgM antibodies to cytomegalovirus during pregnancy.", "content": "IgM antibodies to cytomegalovirus (CMV) could be detected in about 7 per cent of 629 pregnant women whereas in 225 nonpregnant control women of similar age distribution only 2.6 per cent showed CMV IgM antibodies. Intrauterine CMV infections were almost exclusively detected among the CMV IgM positive gravides. The high incidence of CMV IgM antibodies in pregnant women can be possibly explained by an increased rate of CMV reactivations during pregnancy. We were able to show that during CMV reactivation an intrauterine infection might occur.", "contents": "IgM antibodies to cytomegalovirus during pregnancy. IgM antibodies to cytomegalovirus (CMV) could be detected in about 7 per cent of 629 pregnant women whereas in 225 nonpregnant control women of similar age distribution only 2.6 per cent showed CMV IgM antibodies. Intrauterine CMV infections were almost exclusively detected among the CMV IgM positive gravides. The high incidence of CMV IgM antibodies in pregnant women can be possibly explained by an increased rate of CMV reactivations during pregnancy. We were able to show that during CMV reactivation an intrauterine infection might occur."}
{"id": "PMID:193463", "title": "Herpesvirus group antibodies in children with Hodgkin's disease.", "content": "During the period of three years ((1972-1974), serum samples from 60 patients (children and adolescents) with lympho-hematopoietic system diseases were examined for antibodies to all four human herpesviruses. Among these were 26 active Hodgkin's disease (AHD) patients and 6 HD patients with a minimum five years' remission. Simultaneously matched controls (age, sex) of AHD patients were examined. Antibody levels against the viral capsid antigen of Epstein-Barr virus (EBV/VCA) in AHD patients were significantly higher, with overrepresentation of higher titres (greater than or equal to 1:160), than in matched controls. The lowest EBV/VCA antibody titres were in the leukemia-non-Hodgkin's lymphoma patients. We could not prove any significant relationship between cytomegalovirus or herpes simplex virus type 1 antibody titres and AHD or any other disease of lympho-hematopoietic system. The varicella-zoster virus antibody titres in AHD patients were significantly higher than in matched controls. No significant differences in antibodies against EBV/VCA and the other human herpes viruses between the evolution and remission period of AHD patients could be detected. No differences in EBV/VCA antibody titres were observed between the healthy school-children aged 10 to 15 years who were and who were not in contact with a HD patient.", "contents": "Herpesvirus group antibodies in children with Hodgkin's disease. During the period of three years ((1972-1974), serum samples from 60 patients (children and adolescents) with lympho-hematopoietic system diseases were examined for antibodies to all four human herpesviruses. Among these were 26 active Hodgkin's disease (AHD) patients and 6 HD patients with a minimum five years' remission. Simultaneously matched controls (age, sex) of AHD patients were examined. Antibody levels against the viral capsid antigen of Epstein-Barr virus (EBV/VCA) in AHD patients were significantly higher, with overrepresentation of higher titres (greater than or equal to 1:160), than in matched controls. The lowest EBV/VCA antibody titres were in the leukemia-non-Hodgkin's lymphoma patients. We could not prove any significant relationship between cytomegalovirus or herpes simplex virus type 1 antibody titres and AHD or any other disease of lympho-hematopoietic system. The varicella-zoster virus antibody titres in AHD patients were significantly higher than in matched controls. No significant differences in antibodies against EBV/VCA and the other human herpes viruses between the evolution and remission period of AHD patients could be detected. No differences in EBV/VCA antibody titres were observed between the healthy school-children aged 10 to 15 years who were and who were not in contact with a HD patient."}
{"id": "PMID:193464", "title": "A comparative electrophoretic examination of swine vesicular disease virus and Coxsackie B5 virus.", "content": "Purified suspensions of Coxsackie B5 virus and swine vesicular disease virus (SVDV) were prepared by harvesting and purifying cell pack virus. Crossed immunoelectrophoresis was carried out with purified N and H antigen fractions (full and empty particles). Relative migration velocity (RMV) was calculated for the N antigen fraction of 3 SVD viruses (UKG72, HK71 and Italy 66) and 2 Coxsackie B5 viruses (Faulkner and 8068). The prototype strain of Coxsackie B5 virus (Faulkner) had a low RMV almost identical to that of the first isolated strain of SVDV, Italy 66. A recent isolate of Coxsackie B5 virus (8068, isolated in UK in 1973) had a relatively high RMV very close to that of the UKG72 strain of SVDV isolated in the UK in 1972. Also the Hong Kong strain of SVDV (HK71) had a high RMV value. These observations are considered in relation to the emergence of swine vesicular disease.", "contents": "A comparative electrophoretic examination of swine vesicular disease virus and Coxsackie B5 virus. Purified suspensions of Coxsackie B5 virus and swine vesicular disease virus (SVDV) were prepared by harvesting and purifying cell pack virus. Crossed immunoelectrophoresis was carried out with purified N and H antigen fractions (full and empty particles). Relative migration velocity (RMV) was calculated for the N antigen fraction of 3 SVD viruses (UKG72, HK71 and Italy 66) and 2 Coxsackie B5 viruses (Faulkner and 8068). The prototype strain of Coxsackie B5 virus (Faulkner) had a low RMV almost identical to that of the first isolated strain of SVDV, Italy 66. A recent isolate of Coxsackie B5 virus (8068, isolated in UK in 1973) had a relatively high RMV very close to that of the UKG72 strain of SVDV isolated in the UK in 1972. Also the Hong Kong strain of SVDV (HK71) had a high RMV value. These observations are considered in relation to the emergence of swine vesicular disease."}
{"id": "PMID:193467", "title": "[Histochemical study of the phosphomonoesterases of cells producing steroid hormones].", "content": "The results of detection of phosphatases with different substrates in the cells forming steroid hormones in ovaries, testes and adrenals of newborn seals, ovaries of adult seals and adrenals of adult rabbits, dogs and man were compared. The first group of substrates includes sodium glycerophosphate, glucose-1-phosphate, nitrophenylphosphate (Gomori's sulfide method). The second group includes naphthol phosphates AS-BI, AS-MX and AS-BS, whose hydrolysis is determined by simultaneous and successive azocoupling with diazotized benzidine and stable diazotates by fast blue and fast cherry-coloured. Detection of phosphomonesterases in the cells forming steroid hormones with these two groups of substrates gives absolutely different results which are presented in the table. These results are thought to be associated with presence of the isoenzyme, intensively splitting azotholphosphates, but inhibited by the diazonium salt. This isoenzyme is found mainly in the cells producing steroid hormones.", "contents": "[Histochemical study of the phosphomonoesterases of cells producing steroid hormones]. The results of detection of phosphatases with different substrates in the cells forming steroid hormones in ovaries, testes and adrenals of newborn seals, ovaries of adult seals and adrenals of adult rabbits, dogs and man were compared. The first group of substrates includes sodium glycerophosphate, glucose-1-phosphate, nitrophenylphosphate (Gomori's sulfide method). The second group includes naphthol phosphates AS-BI, AS-MX and AS-BS, whose hydrolysis is determined by simultaneous and successive azocoupling with diazotized benzidine and stable diazotates by fast blue and fast cherry-coloured. Detection of phosphomonesterases in the cells forming steroid hormones with these two groups of substrates gives absolutely different results which are presented in the table. These results are thought to be associated with presence of the isoenzyme, intensively splitting azotholphosphates, but inhibited by the diazonium salt. This isoenzyme is found mainly in the cells producing steroid hormones."}
{"id": "PMID:193468", "title": "[Morphogenesis and features of the pathogenesis of adenovirus and chlamydial infections of the conjunctiva].", "content": "Morphogenesis of adenovirus (epidemic keratoconjunctivitis) and chlamydia (paratrachoma) infections was studied on the material consisting of scrapings of the conjunctiva and biopsy specimens taken from 410 patients, by histological, cytological, histo- and cytochemical electron-microscopic and immunohistochemical methods. The investigations conducted showed that the morphogenesis of adenovirus and chlamydia infection of the conjunctiva was underlaid by a complex of pathological disorders including changes in the epithelium, where the cytopathogenic effect of the pathogene was realized, and changes in the conjunctiva tissue proper, the latter being transformed in these infections into the organ of immunogenesis.", "contents": "[Morphogenesis and features of the pathogenesis of adenovirus and chlamydial infections of the conjunctiva]. Morphogenesis of adenovirus (epidemic keratoconjunctivitis) and chlamydia (paratrachoma) infections was studied on the material consisting of scrapings of the conjunctiva and biopsy specimens taken from 410 patients, by histological, cytological, histo- and cytochemical electron-microscopic and immunohistochemical methods. The investigations conducted showed that the morphogenesis of adenovirus and chlamydia infection of the conjunctiva was underlaid by a complex of pathological disorders including changes in the epithelium, where the cytopathogenic effect of the pathogene was realized, and changes in the conjunctiva tissue proper, the latter being transformed in these infections into the organ of immunogenesis."}
{"id": "PMID:193469", "title": "[Several features of cardiac lipid metabolism under conditions of diphteritic intoxication].", "content": "Basing on the collation of data of histochemical and electron-microscopic investigations of the myocardium of rabbits under conditions of diphtherial intoxication and in blocade of the lipolysis processes in the intact and damaged heart, the authors singled out three ways of utilization of lipids by the cardiac muscle. The first way is associated with adsorption of fatty acids from the circulating blood. This way depends on catecholamines and is blocked with nicotinic acid. The second way is determined by splitting of myocardial triacylglycerols. It does not depend on concentrations of catecholamines and can be blocked only following prolonged exposure to nicotinic acid. The third way is associated with intensity of functioning of mitochondria; destruction of the latter brings about liberation of membrane phospholipids which later are transformed into nonesterified fatty acids. This way does not depend on catecholamines and can be inhibited by acid lipids accumulating in the myocardium as a result of impairment of utilization of these lipids.", "contents": "[Several features of cardiac lipid metabolism under conditions of diphteritic intoxication]. Basing on the collation of data of histochemical and electron-microscopic investigations of the myocardium of rabbits under conditions of diphtherial intoxication and in blocade of the lipolysis processes in the intact and damaged heart, the authors singled out three ways of utilization of lipids by the cardiac muscle. The first way is associated with adsorption of fatty acids from the circulating blood. This way depends on catecholamines and is blocked with nicotinic acid. The second way is determined by splitting of myocardial triacylglycerols. It does not depend on concentrations of catecholamines and can be blocked only following prolonged exposure to nicotinic acid. The third way is associated with intensity of functioning of mitochondria; destruction of the latter brings about liberation of membrane phospholipids which later are transformed into nonesterified fatty acids. This way does not depend on catecholamines and can be inhibited by acid lipids accumulating in the myocardium as a result of impairment of utilization of these lipids."}
{"id": "PMID:193470", "title": "[Current trends in the study of phagocytosis and non-specific resistance].", "content": "Phagocytosis begins with exocytosis--\"extrarapid\" discharge of bactericidal proteins and factors of permeability into the extracellular medium. A viewpoint was put forward on an \"avalanch-like\" character of the outcome of cationic proteins from leukocyte granules in inflammation and their participation in formation of a nonphagocytic type of resistance. In phagocytosis bacteria perish due to the myeloperoxidase system, lysozyme,  lactoferin and nonenzymic cationic proteins. Hereditary deficit of the above-mentioned substances leads to intraleukocytic microbicidal insufficiency, a drastic decrease in the nonspecific resistance of the organism and to development of fatal granulomatous disease, and to other forms of pathology associated with genetic defects of the bactericidal systems of leukocytes.", "contents": "[Current trends in the study of phagocytosis and non-specific resistance]. Phagocytosis begins with exocytosis--\"extrarapid\" discharge of bactericidal proteins and factors of permeability into the extracellular medium. A viewpoint was put forward on an \"avalanch-like\" character of the outcome of cationic proteins from leukocyte granules in inflammation and their participation in formation of a nonphagocytic type of resistance. In phagocytosis bacteria perish due to the myeloperoxidase system, lysozyme,  lactoferin and nonenzymic cationic proteins. Hereditary deficit of the above-mentioned substances leads to intraleukocytic microbicidal insufficiency, a drastic decrease in the nonspecific resistance of the organism and to development of fatal granulomatous disease, and to other forms of pathology associated with genetic defects of the bactericidal systems of leukocytes."}
{"id": "PMID:193471", "title": "[Russel bodies in the duodenal mucosa in ulcer disease].", "content": "A total of 103 specimens of the duodenum mucosa incised during the resection of the stomach in different variants of the course of peptic ulcer were studied. It was shown that Russell's bodies (RB) in the mucosa's layer proper were formed by cellular elements analogous to immunoglobulinocytes of the lymph nodes and spleen of the laboratory animals which had been subjected to an experimental stimulation of immunogenesis. Peculiar patterns of contacts of RB with the mast cells and possible significance of these contacts are discussed. On the basis of the data obtained the conclusion was drawn that elimination of the RB substrate in the duodenum mucosa was realized in two directions: a) centripetal by penetration of the substrate into the lymphatic and blood vessels; and b) centrifugal, by its evacuation into the lumen of the alimentary canal.", "contents": "[Russel bodies in the duodenal mucosa in ulcer disease]. A total of 103 specimens of the duodenum mucosa incised during the resection of the stomach in different variants of the course of peptic ulcer were studied. It was shown that Russell's bodies (RB) in the mucosa's layer proper were formed by cellular elements analogous to immunoglobulinocytes of the lymph nodes and spleen of the laboratory animals which had been subjected to an experimental stimulation of immunogenesis. Peculiar patterns of contacts of RB with the mast cells and possible significance of these contacts are discussed. On the basis of the data obtained the conclusion was drawn that elimination of the RB substrate in the duodenum mucosa was realized in two directions: a) centripetal by penetration of the substrate into the lymphatic and blood vessels; and b) centrifugal, by its evacuation into the lumen of the alimentary canal."}
{"id": "PMID:193472", "title": "[Genetic syndromes of multiple congenital developmental defects].", "content": "Analysis of developmental defects in 615 children who had died in hospitals in Minsk during the 5-year period (1971--1975)showed that in 274 children defects were multiple. This number includes 78 children with chromosomal diseases and 37 children with genic syndromes of multiple congenital malformations (MCM). The total number of genic syndromes of MCM is extremely great, at present over 250 of them are known. Analysis of the available literature and the authors' own findings made it possible to develop criteria of morphological diagnosis of genic syndromes of MCM with due account for different diagnostic significance of various defects. Genealogical studies and estimation of population incidence of individual malformations are also necessary for diagnosis of genic syndromes of MCM and identification of new syndromes. An etiological classification of MCM and that of genic syndromes of MCM are considered on the basis of isolation of similar clinical forms, which are of important for differential diagnosis.", "contents": "[Genetic syndromes of multiple congenital developmental defects]. Analysis of developmental defects in 615 children who had died in hospitals in Minsk during the 5-year period (1971--1975)showed that in 274 children defects were multiple. This number includes 78 children with chromosomal diseases and 37 children with genic syndromes of multiple congenital malformations (MCM). The total number of genic syndromes of MCM is extremely great, at present over 250 of them are known. Analysis of the available literature and the authors' own findings made it possible to develop criteria of morphological diagnosis of genic syndromes of MCM with due account for different diagnostic significance of various defects. Genealogical studies and estimation of population incidence of individual malformations are also necessary for diagnosis of genic syndromes of MCM and identification of new syndromes. An etiological classification of MCM and that of genic syndromes of MCM are considered on the basis of isolation of similar clinical forms, which are of important for differential diagnosis."}
{"id": "PMID:193473", "title": "[Tumors of the liver, biliary tracts and pancreas in monkeys].", "content": "The article deals with spontaneous tumours of the liver, biliary tract, and pancreas observed in monkeys of the Sukhumi Simian Nursery during the period of 1960--1974. Among tumours of the liver hepatoadenomas predominated: they were revealed in 4 macaco rhesuses, one green marmoset. In a young baboon hamadryad adenomatous hyperplasia was observed to be developed against the background of hepatocirrhosis. All three cases of tumours of the biliary tract in baboons hamadryad were classified as adenocarcinomas. Descriptions of liver cell anaplastic carcinoma with extensive metastasizing in Macaco rhesus, those of insuloma of the pancreas in the same species, and of papilary duct carcinoma of the head of the pancreas in a red ape (Erythrocebus patas) are presented for the first time. All the monkeys with tumours, but one, were at the age over 10 years and were born in the Nursery, or had been brought to it more than 7 years before.", "contents": "[Tumors of the liver, biliary tracts and pancreas in monkeys]. The article deals with spontaneous tumours of the liver, biliary tract, and pancreas observed in monkeys of the Sukhumi Simian Nursery during the period of 1960--1974. Among tumours of the liver hepatoadenomas predominated: they were revealed in 4 macaco rhesuses, one green marmoset. In a young baboon hamadryad adenomatous hyperplasia was observed to be developed against the background of hepatocirrhosis. All three cases of tumours of the biliary tract in baboons hamadryad were classified as adenocarcinomas. Descriptions of liver cell anaplastic carcinoma with extensive metastasizing in Macaco rhesus, those of insuloma of the pancreas in the same species, and of papilary duct carcinoma of the head of the pancreas in a red ape (Erythrocebus patas) are presented for the first time. All the monkeys with tumours, but one, were at the age over 10 years and were born in the Nursery, or had been brought to it more than 7 years before."}
{"id": "PMID:193474", "title": "Blindness of cerebral origin in acute intermittent porphyria. Report of a case and postmortem examination.", "content": "Sudden permanent blindness of cerebral origin, in addition to severe abdominal pain, hypertension, convulsions, and peripheral neuropathy developed in a 21-year-old woman, a victim of acute intermittent porphyria. Findings of the pathological examination of the brain showed extensive infarction in both occipital lobes. The pathological changes were consistent with anoxia. We discuss and review the literature of the possibility of \"vasospasm\" of both posterior cerebral arteries. Follow-up studies with serial EEG showed either focal epileptogenic activity or diffuse slow waves. The most consistent epileptic discharges were found in the occipital regions. The favorable response to the treatment of seizures with carbamazepine in this patient might encourage further clinical trials.", "contents": "Blindness of cerebral origin in acute intermittent porphyria. Report of a case and postmortem examination. Sudden permanent blindness of cerebral origin, in addition to severe abdominal pain, hypertension, convulsions, and peripheral neuropathy developed in a 21-year-old woman, a victim of acute intermittent porphyria. Findings of the pathological examination of the brain showed extensive infarction in both occipital lobes. The pathological changes were consistent with anoxia. We discuss and review the literature of the possibility of \"vasospasm\" of both posterior cerebral arteries. Follow-up studies with serial EEG showed either focal epileptogenic activity or diffuse slow waves. The most consistent epileptic discharges were found in the occipital regions. The favorable response to the treatment of seizures with carbamazepine in this patient might encourage further clinical trials."}
{"id": "PMID:193476", "title": "Effects of a single methylprednisolone dose on a facilitatory response of mammalian motor nerve.", "content": "Long-term glucocorticoid dosing directly enhances a facilitatory function of cat soleus motor nerve terminals. Posttetanic potentiation (PTP) of soleus contraction is a manifestation of this prejunctional facilitation. The present study demonstrates that the same enhancement of facilitation is produced with a single large intravenous dose methylprednisolone. The single dosing method, however, showed an initial suppression of facilitation that neared recovery in four hours. Thereafter, the characteristic augmentation of prejunctional facilitation emerged, peaking in 24 hours. Return to control required four days. Knowledge of this time course enabled centrally disconnected motor nerve endings to be identified as the site of both phases of the steroid action. Since the neuromuscular facilitation studied is equivalent to that triggered by neostigmine-like drugs, the results infer that the antimyasthenic effect of glucocorticoids may involve a direct action on motor nerve endings.", "contents": "Effects of a single methylprednisolone dose on a facilitatory response of mammalian motor nerve. Long-term glucocorticoid dosing directly enhances a facilitatory function of cat soleus motor nerve terminals. Posttetanic potentiation (PTP) of soleus contraction is a manifestation of this prejunctional facilitation. The present study demonstrates that the same enhancement of facilitation is produced with a single large intravenous dose methylprednisolone. The single dosing method, however, showed an initial suppression of facilitation that neared recovery in four hours. Thereafter, the characteristic augmentation of prejunctional facilitation emerged, peaking in 24 hours. Return to control required four days. Knowledge of this time course enabled centrally disconnected motor nerve endings to be identified as the site of both phases of the steroid action. Since the neuromuscular facilitation studied is equivalent to that triggered by neostigmine-like drugs, the results infer that the antimyasthenic effect of glucocorticoids may involve a direct action on motor nerve endings."}
{"id": "PMID:193477", "title": "Antimyasthenic action of corticosteroids.", "content": "Tests were made in vitro fo the action of prednisolone on nerve backfiring, muscle twitches, tetanus decay rates, miniature end-plate potential amplitude and frequency, and the block induced by curare, hemicholinium, and excess magnesium. At about 0.1 mM concentration, the steroid showed no 'veratrinic' or decurarizing action, and the probability of transmitter release was not increased in 10mM Mg++. Moreover, when acetylcholine stores were depleted in hemicholinium, there was no evidence of repair by steroid. The results are taken to mean that prednisolone and congeners do not owe their therapeutic efficacy in myasthenia to actions at the neuromuscular junction. It is therefore concluded that the clinical benefits from steroids are related to systemic, possibly immunosuppressive effects.", "contents": "Antimyasthenic action of corticosteroids. Tests were made in vitro fo the action of prednisolone on nerve backfiring, muscle twitches, tetanus decay rates, miniature end-plate potential amplitude and frequency, and the block induced by curare, hemicholinium, and excess magnesium. At about 0.1 mM concentration, the steroid showed no 'veratrinic' or decurarizing action, and the probability of transmitter release was not increased in 10mM Mg++. Moreover, when acetylcholine stores were depleted in hemicholinium, there was no evidence of repair by steroid. The results are taken to mean that prednisolone and congeners do not owe their therapeutic efficacy in myasthenia to actions at the neuromuscular junction. It is therefore concluded that the clinical benefits from steroids are related to systemic, possibly immunosuppressive effects."}
{"id": "PMID:193478", "title": "Characteristic early electroencephalographic changes in herpes simplex encephalitis.", "content": "We review electroencephalograms taken from 17 patients with severe meningoencephalitis within seven days of onset of CNS symptoms and prior to cortical brain biopsies. All patients had CNS disease clinically compatible with the diagnosis of herpes simplex encephalitis (HSE). The diagnosis was demonstrated by the isolation of virus from the brain in five patients (group 1) but considered highly unlikely in the other 12 patients (group 2) by negative immunofluorescent studies and failure of viral isolation from the brain tissue. Abnormal but nonspecific EEGs with diffuse or focal slowing were found in all patients. Distinctive high-voltage, 1-cycle-per-2-to-3 seconds periodic sharp waves from unilateral temporal lobes were seen only in three of the five patients with virologically proved HSE but in none of the 12 patients without viral isolation. This EEG pattern is strikingly similar in all three patients, regardless of their age, and may be specific for the early diagnosis of HSE prior to brain biopsy. The EEGs of the other two patients with proved HSE did not contain such abnormalities. Athough periodic EEGs with some resemblance to those previously described may occur in other CNS disorders, their presence strongly suggests the diagnosis of HSE when recorded from patients with viral meningoencephalitis. Moreover, EEGs may help locate the best site for cerebral biopsy since maximal yield of the virus in this study was from unilateral temperoal lobes corresponding with the site of local EEG changes.", "contents": "Characteristic early electroencephalographic changes in herpes simplex encephalitis. We review electroencephalograms taken from 17 patients with severe meningoencephalitis within seven days of onset of CNS symptoms and prior to cortical brain biopsies. All patients had CNS disease clinically compatible with the diagnosis of herpes simplex encephalitis (HSE). The diagnosis was demonstrated by the isolation of virus from the brain in five patients (group 1) but considered highly unlikely in the other 12 patients (group 2) by negative immunofluorescent studies and failure of viral isolation from the brain tissue. Abnormal but nonspecific EEGs with diffuse or focal slowing were found in all patients. Distinctive high-voltage, 1-cycle-per-2-to-3 seconds periodic sharp waves from unilateral temporal lobes were seen only in three of the five patients with virologically proved HSE but in none of the 12 patients without viral isolation. This EEG pattern is strikingly similar in all three patients, regardless of their age, and may be specific for the early diagnosis of HSE prior to brain biopsy. The EEGs of the other two patients with proved HSE did not contain such abnormalities. Athough periodic EEGs with some resemblance to those previously described may occur in other CNS disorders, their presence strongly suggests the diagnosis of HSE when recorded from patients with viral meningoencephalitis. Moreover, EEGs may help locate the best site for cerebral biopsy since maximal yield of the virus in this study was from unilateral temperoal lobes corresponding with the site of local EEG changes."}
{"id": "PMID:193479", "title": "Increased cellular responsiveness to epinephrine in primary open-angle glaucoma.", "content": "The concentration of I-epinephrine hydrochloride necessary to inhibit lymphocyte transformation by 50% (I50 value) was determined in vitro for nine patients with primary open-angle glaucoma (POAG) and in seven controls. The lymphocytes of the patients with POAG were significantly (P less than .05) more responsive. This result is consistent with the hypothesis that patients with POAG have an increased responsiveness to agents that elevate intracellular cyclic adenosine monophosphate levels.", "contents": "Increased cellular responsiveness to epinephrine in primary open-angle glaucoma. The concentration of I-epinephrine hydrochloride necessary to inhibit lymphocyte transformation by 50% (I50 value) was determined in vitro for nine patients with primary open-angle glaucoma (POAG) and in seven controls. The lymphocytes of the patients with POAG were significantly (P less than .05) more responsive. This result is consistent with the hypothesis that patients with POAG have an increased responsiveness to agents that elevate intracellular cyclic adenosine monophosphate levels."}
{"id": "PMID:193482", "title": "Watery diarrhoea (WDHA) syndrome associated with carcinoma of the lung.", "content": "A patient with bronchial carcinoma presented with profuse watery diarrhoea, hypokalaemia and hypochlorhydria. Laparotomy appeared to exclude the usual cause, a pancreatic islet-cell tumour. Relief of the diarrhoea was achieved only with prednisone therapy. Evidence is adduced to implicate a humoral factor produced by the tumour, although in this case, the serum VIP level was not elevated.", "contents": "Watery diarrhoea (WDHA) syndrome associated with carcinoma of the lung. A patient with bronchial carcinoma presented with profuse watery diarrhoea, hypokalaemia and hypochlorhydria. Laparotomy appeared to exclude the usual cause, a pancreatic islet-cell tumour. Relief of the diarrhoea was achieved only with prednisone therapy. Evidence is adduced to implicate a humoral factor produced by the tumour, although in this case, the serum VIP level was not elevated."}
{"id": "PMID:193486", "title": "Enzyme histochemistry of rat folic acid nephropathy.", "content": "One hour after a single i.v. dose of 250 mg/kg folic acid, the straight portion of distal tubules in the outer medulla of rat kidneys showed a distinct reduction in succinate dehydrogenase, NADH2-diaphorase, glutamate dehydrogenase, cytochrome oxydase, Na+/K+-ATPase, and acid phosphatase activity. In contrast, the proximal tubules exhibited only a reduction in glutamate dehydrogenase and alkaline phosphatase activity. At this time the straight portion of the distal tubules, whose enzyme activity had changed, showed partly regressive epithelial changes. 24 hours after folic acid administration an even greater reduction in enzyme activity had occurred in the straight portion of distal tubules; these structures also became dilated. The adjacent collecting tubules and the corresponding proximal tubules were also severely dilated, the proximal tubules showing a loss in enzyme acitivities similar to those observed in the distal tubules. 48 hours after folic acid administration the changes largely resembled those observed after 24 hours, but were more pronounced. At this time a tubular regeneration was observed. 72 hours after folic administration extensive normalization of the histological and histochemical changes had occured. It is postulated that a disturbance of the hairpin counter-current mechanism occurs as a result of a direct, concentration-dependent effect of folic acid on the enzymes of the energy supplying metabolism. A dilation in the region of the loop of Henle and the collecting tubules occurs subsequently.", "contents": "Enzyme histochemistry of rat folic acid nephropathy. One hour after a single i.v. dose of 250 mg/kg folic acid, the straight portion of distal tubules in the outer medulla of rat kidneys showed a distinct reduction in succinate dehydrogenase, NADH2-diaphorase, glutamate dehydrogenase, cytochrome oxydase, Na+/K+-ATPase, and acid phosphatase activity. In contrast, the proximal tubules exhibited only a reduction in glutamate dehydrogenase and alkaline phosphatase activity. At this time the straight portion of the distal tubules, whose enzyme activity had changed, showed partly regressive epithelial changes. 24 hours after folic acid administration an even greater reduction in enzyme activity had occurred in the straight portion of distal tubules; these structures also became dilated. The adjacent collecting tubules and the corresponding proximal tubules were also severely dilated, the proximal tubules showing a loss in enzyme acitivities similar to those observed in the distal tubules. 48 hours after folic acid administration the changes largely resembled those observed after 24 hours, but were more pronounced. At this time a tubular regeneration was observed. 72 hours after folic administration extensive normalization of the histological and histochemical changes had occured. It is postulated that a disturbance of the hairpin counter-current mechanism occurs as a result of a direct, concentration-dependent effect of folic acid on the enzymes of the energy supplying metabolism. A dilation in the region of the loop of Henle and the collecting tubules occurs subsequently."}
{"id": "PMID:193485", "title": "Evidence for head-head interactions in myosin from cardiac and skeletal muscles.", "content": "1. Binding of MG-ADP to both heart and fast skeletal myosin was found with 3 methods to proceed in 2 steps. One mole of MG-ADP binds with high affinity (K approximately equal to 10(6) M-1) and subsequently a second with lower affinity (K approximately equal to 10(2)-10(4) M-1) per myosin. Only one mole of MG-ADP was found to bind with the high affinity to isolated myosin heads. This implies that binding of MG-ADP to intact myosin exhibits negative cooperativity. 2. When a nucleotide is bound, the 2 heads of a single myosin molecule adopt different conformations since on each head a different type of essential thiol group was found to be the most reactive towards N-ethylmaleimide. In the presence of MG-pyrophosphate a thiol-1 is the most reactive essential group in both heads. Therefore, the nucleoside moiety seems to be required for this latter type of head-head interaction.", "contents": "Evidence for head-head interactions in myosin from cardiac and skeletal muscles. 1. Binding of MG-ADP to both heart and fast skeletal myosin was found with 3 methods to proceed in 2 steps. One mole of MG-ADP binds with high affinity (K approximately equal to 10(6) M-1) and subsequently a second with lower affinity (K approximately equal to 10(2)-10(4) M-1) per myosin. Only one mole of MG-ADP was found to bind with the high affinity to isolated myosin heads. This implies that binding of MG-ADP to intact myosin exhibits negative cooperativity. 2. When a nucleotide is bound, the 2 heads of a single myosin molecule adopt different conformations since on each head a different type of essential thiol group was found to be the most reactive towards N-ethylmaleimide. In the presence of MG-pyrophosphate a thiol-1 is the most reactive essential group in both heads. Therefore, the nucleoside moiety seems to be required for this latter type of head-head interaction."}
{"id": "PMID:193520", "title": "[Dose-dependent effects on phenobarbital on microsomal liver enzymes of chicken embryos (author's transl)].", "content": "Levels of cytochrome P-450 and the activities of amino-pyrinedemethylase and p-nitrophenol-UDP-glucuronyltransferase were measured in homogenates and microsomes of 16 to 19 day old chicken embryos exposed in ovo to phenobarbital. The activities of glucose-6-phosphatase were measured on the 19th day of incubation. After the highest dose of 3 X 8 mg phenobarbital, cytochrome P-450 increased 3-6fold, aminopyrinedemethylase activity 7fold and the activity of p-nitrophenol-UDP-glucuronyltransferase 3fold. Glucose-6-phosphatase activity was not increased but decreased. Corresponding to the given dose of phenobarbital (3X3, 3X4, 3X6, 3X8 mg) into the yolk sac an increase in enzyme activity levels mentioned above could as a rule be demonstrated at the level of p less than 0.0025. Calculated microsomal protein amounted to 43.0+/-6.5 mg/g liver.", "contents": "[Dose-dependent effects on phenobarbital on microsomal liver enzymes of chicken embryos (author's transl)]. Levels of cytochrome P-450 and the activities of amino-pyrinedemethylase and p-nitrophenol-UDP-glucuronyltransferase were measured in homogenates and microsomes of 16 to 19 day old chicken embryos exposed in ovo to phenobarbital. The activities of glucose-6-phosphatase were measured on the 19th day of incubation. After the highest dose of 3 X 8 mg phenobarbital, cytochrome P-450 increased 3-6fold, aminopyrinedemethylase activity 7fold and the activity of p-nitrophenol-UDP-glucuronyltransferase 3fold. Glucose-6-phosphatase activity was not increased but decreased. Corresponding to the given dose of phenobarbital (3X3, 3X4, 3X6, 3X8 mg) into the yolk sac an increase in enzyme activity levels mentioned above could as a rule be demonstrated at the level of p less than 0.0025. Calculated microsomal protein amounted to 43.0+/-6.5 mg/g liver."}
{"id": "PMID:193521", "title": "Myogenic foam cells in explants of fatty dots and streaks from rabbit aorta. Morphological studies.", "content": "Present studies indicate that in explants of early atherosclerotic lesions removed from aortae of young rabbits on a 1% hypercholesterolemic diet for four and seven weeks respectively, myogenic foam cells (MCF's) were capable of emigrating into the culture medium and maintained their ability to produce microfibrils, elastic tissue elements, and collagen fibrils. In explants of the smallest lesions (fatty dots and small streaks) the MFC's divided prior to, or while emigrating. At the interphase between the primary tissue and the culture medium they contained in intracytoplasmic vacuoles fragments of elastic tissue and extraneous substances which were reminiscent of cellular debris. It is possible that this phenomenon represents a true phagocytic property of the MFC's. All formed extracellular connective tissue components were also produced by the emigrated MFC's in the tissue surrounding the cellular outgrowth. In the large fatty streaks cell division was observed at the interphase between the tissue and culture medium, but not within the substance of the explant; here cellular necrosis was prominent. The fat inclusions in the MFC's of explants and the outgrowth had the appearance of conglomerateds of unorganized, and only at times concentric, membranous profiles rather than that of homogeneous droplets observed by electron microscopy in these cells in tissue sections. In the outgrowth from explants of normal aortic areas adjacent to the lesions a moderate number of smoot muscle cells contained fat inclusions; these were almost totally absent in cells of the primary aortic cultures from normal aortae. It is conceivable that the migratory and phagocytic properties of the MFC's observed in the present study relate to some aspects of regression of atherosclerotic lesions; this, however, remains highly speculative at present.", "contents": "Myogenic foam cells in explants of fatty dots and streaks from rabbit aorta. Morphological studies. Present studies indicate that in explants of early atherosclerotic lesions removed from aortae of young rabbits on a 1% hypercholesterolemic diet for four and seven weeks respectively, myogenic foam cells (MCF's) were capable of emigrating into the culture medium and maintained their ability to produce microfibrils, elastic tissue elements, and collagen fibrils. In explants of the smallest lesions (fatty dots and small streaks) the MFC's divided prior to, or while emigrating. At the interphase between the primary tissue and the culture medium they contained in intracytoplasmic vacuoles fragments of elastic tissue and extraneous substances which were reminiscent of cellular debris. It is possible that this phenomenon represents a true phagocytic property of the MFC's. All formed extracellular connective tissue components were also produced by the emigrated MFC's in the tissue surrounding the cellular outgrowth. In the large fatty streaks cell division was observed at the interphase between the tissue and culture medium, but not within the substance of the explant; here cellular necrosis was prominent. The fat inclusions in the MFC's of explants and the outgrowth had the appearance of conglomerateds of unorganized, and only at times concentric, membranous profiles rather than that of homogeneous droplets observed by electron microscopy in these cells in tissue sections. In the outgrowth from explants of normal aortic areas adjacent to the lesions a moderate number of smoot muscle cells contained fat inclusions; these were almost totally absent in cells of the primary aortic cultures from normal aortae. It is conceivable that the migratory and phagocytic properties of the MFC's observed in the present study relate to some aspects of regression of atherosclerotic lesions; this, however, remains highly speculative at present."}
{"id": "PMID:193522", "title": "Cholesterol ester accumulation in cultured aortic smooth muscle cells. Induction of cholesterol ester retention by chloroquine and low density lipoprotein and its reversion by mixtures of high density apolipoprotein and sphingomyelin.", "content": "Accretion of cholesterol ester was studied in rat aortic smooth muscle cells in culture. Confluent multilayers of smooth muscle cells were exposed to human low density lipoprotein (LDL) and chloroquine and this treatment resulted in a very marked increase in cellular cholesterol ester. The degree of enrichment in cholesterol ester was related inversely to the cell density in the petri dish and was maximal in 48 h. The morphological changes after 48 h incubation with chloroquine and LDL consisted of accumulation of numerous membrane-bound inclusions containing electron-dense and electron-lucent material, some of which resembled secondary lysosomes. These changes resembled some of the changes observed in human and experimental atheromatosis. Similar inclusions were seen also in cultured human skin fibroblasts which accumulated large amounts of cholesterol ester during 48 h incubation with LDL and chloroquine. Removal of the accumulated cellular cholesterol ester was studied in the two cell types and it was markedly enhanced in the presence of lipoprotein-deficient serum and high density apolipoprotein-sphingomyelin mixture. The morphological findings after 24 h of post incubation revealed the presence of empty vacuoles, membrane whorls and cytoplasmic lipid droplets. The present results indicate that aortic smooth muscle cells in culture can serve as a good model to study the role of the lysosomal system in atherogenesis.", "contents": "Cholesterol ester accumulation in cultured aortic smooth muscle cells. Induction of cholesterol ester retention by chloroquine and low density lipoprotein and its reversion by mixtures of high density apolipoprotein and sphingomyelin. Accretion of cholesterol ester was studied in rat aortic smooth muscle cells in culture. Confluent multilayers of smooth muscle cells were exposed to human low density lipoprotein (LDL) and chloroquine and this treatment resulted in a very marked increase in cellular cholesterol ester. The degree of enrichment in cholesterol ester was related inversely to the cell density in the petri dish and was maximal in 48 h. The morphological changes after 48 h incubation with chloroquine and LDL consisted of accumulation of numerous membrane-bound inclusions containing electron-dense and electron-lucent material, some of which resembled secondary lysosomes. These changes resembled some of the changes observed in human and experimental atheromatosis. Similar inclusions were seen also in cultured human skin fibroblasts which accumulated large amounts of cholesterol ester during 48 h incubation with LDL and chloroquine. Removal of the accumulated cellular cholesterol ester was studied in the two cell types and it was markedly enhanced in the presence of lipoprotein-deficient serum and high density apolipoprotein-sphingomyelin mixture. The morphological findings after 24 h of post incubation revealed the presence of empty vacuoles, membrane whorls and cytoplasmic lipid droplets. The present results indicate that aortic smooth muscle cells in culture can serve as a good model to study the role of the lysosomal system in atherogenesis."}
{"id": "PMID:193523", "title": "Effect of lipoprotein-X on hepatic cholesterol synthesis.", "content": "The effect of different lipoproteins (lipoprotein-X and lipoprotein-B; LP-X and LP-B) on hepatic cholesterol synthesis was studied in vivo in rats. Lipoproteins were continuously infused into rats for 16 hours so that 24 mg cholesterol/100 g body weight were applied. Serum cholesterol level was nearly doubled after the infusion period. Lipoprotein electrophoresis revealed the predominance of the infused lipoprotein in the serum. LP-B infusion caused a reduction of cholesterol synthesis (42% of control values) and reduced the increased cholesterol synthesis of bile fistula rats to values below normal. LP-X did not reduce hepatic cholesterol synthesis significantly nor did it normalize the enhanced synthesis following biliary diversion. However, hepatic free cholesterol concentration increased after LP-X infusion. The effect of LP-X on liver cholesterol synthesis is similar to that of lecithin: cholesterol dispersions. The failure of LP-X to exert a feedback inhibition on cholesterol synthesis may therefore contribute to the mechanism of hypercholesterolemia in obstructive jaundice.", "contents": "Effect of lipoprotein-X on hepatic cholesterol synthesis. The effect of different lipoproteins (lipoprotein-X and lipoprotein-B; LP-X and LP-B) on hepatic cholesterol synthesis was studied in vivo in rats. Lipoproteins were continuously infused into rats for 16 hours so that 24 mg cholesterol/100 g body weight were applied. Serum cholesterol level was nearly doubled after the infusion period. Lipoprotein electrophoresis revealed the predominance of the infused lipoprotein in the serum. LP-B infusion caused a reduction of cholesterol synthesis (42% of control values) and reduced the increased cholesterol synthesis of bile fistula rats to values below normal. LP-X did not reduce hepatic cholesterol synthesis significantly nor did it normalize the enhanced synthesis following biliary diversion. However, hepatic free cholesterol concentration increased after LP-X infusion. The effect of LP-X on liver cholesterol synthesis is similar to that of lecithin: cholesterol dispersions. The failure of LP-X to exert a feedback inhibition on cholesterol synthesis may therefore contribute to the mechanism of hypercholesterolemia in obstructive jaundice."}
{"id": "PMID:193524", "title": "Pharmacokinetics of clofibrate in familial hypercholesterolemia.", "content": "Some patients with familial hypercholesterolemia (FHC, type II) are highly responsive to the cholesterol-lowering effect of clofibrate, while others are not only resistant to this effect but may even show an increase in plasma beta-lipoproteins. In an attempt to find an explanation for these striking differences, we have studied the pharmacokinetics of clofibrate in FHC patients at both extremes of responsiveness. The results disclosed several major differences between the two groups. Plasma clofibric acid (CPIB) measured during the chronic administration of the drug was significantly higher in the responders than in the non-responders, whether all patients in each group or only those with tendon xanthomas were considered. Plasma CPIB concentrations were negatively correlated with body weight in the responders but not in CPIB-resistant patients. They were also inversely proportional to decreases in plasma beta-lipoprotein cholesterol after chronic clofibrate administration in the responsive group, but directly proportional to increases in the non-responders. Increasing the dose of clofibrate from 2 to 3 g/day in CPIB-resistant patients always resulted in an increase in plasma CPIB levels, but this was followed in some patients by a decrease and in others by an increase in plasma beta-lipoprotein cholesterol concentrations, so that the overall effect was not statistically significant. The half-life of plasma CPIB was measured over 48 h after a single 1-g dose of clofibrate in patients who had not received this drug for at least 3 weeks. Half-life was significantly longer in the responsive patients. In addition, the bioavailability and the rate of absorption of clofibrate tended to be higher in this group than in the resistant patients. We suspect that both groups differ not only in the metabolic handling of clofibrate but also in some aspect of their beta-lipoprotein cholesterol metabolism.", "contents": "Pharmacokinetics of clofibrate in familial hypercholesterolemia. Some patients with familial hypercholesterolemia (FHC, type II) are highly responsive to the cholesterol-lowering effect of clofibrate, while others are not only resistant to this effect but may even show an increase in plasma beta-lipoproteins. In an attempt to find an explanation for these striking differences, we have studied the pharmacokinetics of clofibrate in FHC patients at both extremes of responsiveness. The results disclosed several major differences between the two groups. Plasma clofibric acid (CPIB) measured during the chronic administration of the drug was significantly higher in the responders than in the non-responders, whether all patients in each group or only those with tendon xanthomas were considered. Plasma CPIB concentrations were negatively correlated with body weight in the responders but not in CPIB-resistant patients. They were also inversely proportional to decreases in plasma beta-lipoprotein cholesterol after chronic clofibrate administration in the responsive group, but directly proportional to increases in the non-responders. Increasing the dose of clofibrate from 2 to 3 g/day in CPIB-resistant patients always resulted in an increase in plasma CPIB levels, but this was followed in some patients by a decrease and in others by an increase in plasma beta-lipoprotein cholesterol concentrations, so that the overall effect was not statistically significant. The half-life of plasma CPIB was measured over 48 h after a single 1-g dose of clofibrate in patients who had not received this drug for at least 3 weeks. Half-life was significantly longer in the responsive patients. In addition, the bioavailability and the rate of absorption of clofibrate tended to be higher in this group than in the resistant patients. We suspect that both groups differ not only in the metabolic handling of clofibrate but also in some aspect of their beta-lipoprotein cholesterol metabolism."}
{"id": "PMID:193525", "title": "Treatment of hypertriglyceridemia with metformin. Effectiveness and anal\u1ef3sis of results.", "content": "The triglyceride-lowering effect of metformin (N,N-dimethylbiguanide) was tested in a series of patients with stable hypertriglyceridemia (types IIB, III and IV) and with variable degrees of glucose intolerance. Metformin caused a 38% mean decrease of plasma triglycerides. A selective decrease of very low density lipoprotein cholesterol was observed without reciprocal increase of low density lipoproteins. Thirty patients completed the study. Eighteen, who showed a hypotriglyceridemic effect exceeding 30%, were considered as \"Responders\"; the other 12, where the effect was negligible, were considered as \"Non-Responder\". Analysis of the pre-and post-treatment glucose tolerance tests of Responders and Non-Responders showed that the former had, on the average, a normal glucose tolerance and insulin secretion, whereas the latter had an impaired glucose tolerance with increased insulin secretion. These parameters were only slightly modified by metformin. The conclusions of this study support the hypothesis that biguanides exert a triglyceride-lowering effect by decreasing lipoprotein secretion, independent of changes in glucose tolerance and/or insulin secretion.", "contents": "Treatment of hypertriglyceridemia with metformin. Effectiveness and anal\u1ef3sis of results. The triglyceride-lowering effect of metformin (N,N-dimethylbiguanide) was tested in a series of patients with stable hypertriglyceridemia (types IIB, III and IV) and with variable degrees of glucose intolerance. Metformin caused a 38% mean decrease of plasma triglycerides. A selective decrease of very low density lipoprotein cholesterol was observed without reciprocal increase of low density lipoproteins. Thirty patients completed the study. Eighteen, who showed a hypotriglyceridemic effect exceeding 30%, were considered as \"Responders\"; the other 12, where the effect was negligible, were considered as \"Non-Responder\". Analysis of the pre-and post-treatment glucose tolerance tests of Responders and Non-Responders showed that the former had, on the average, a normal glucose tolerance and insulin secretion, whereas the latter had an impaired glucose tolerance with increased insulin secretion. These parameters were only slightly modified by metformin. The conclusions of this study support the hypothesis that biguanides exert a triglyceride-lowering effect by decreasing lipoprotein secretion, independent of changes in glucose tolerance and/or insulin secretion."}
{"id": "PMID:193526", "title": "On the rise in low density and high density lipoproteins in response to the treatment of hypertriglyceridaemias in type IV and type V hyperlipoproteinaemias.", "content": "In Type V hyperlipoproteinaemia the concentration of LDL and HDL cholesterol is low. When the hypertriglyceridaemia is normalized, either by diet or micotinic acid, both LDL and HDL increase. In Type IV hyperlipoproteinaemia both LDL and HDL cholesterol decrease with increasing VLDL levels. During treatment of Type IV the change in LDL cholesterol is linearly related to the pretreatment LDL concentration so that higher LDL levels will fall and the lower will rise. HDL levels will also rise. The fall in VLDL during treatment is rapid and the rise in LDL also occurs rapidly indicating a relationship between these two reciprocal changes. HDL cholesterol, however, however, remains constant some time after VLDL has reached its lowest level and the rise occurs later indicating another mechanism than for LDL. These changes in the three major lipoprotein classes deserve clinical attention. While both the fall in VLDL and the rise in HDL may be benefical from the point of view of atherosclerosis the rise in LDL may be harmful. These is at present no way to evaluate the effect of these complex changes. However, these findings stress the imporance of considering changes in lipoprotein levels and not only in total serum triglycerides and cholesterol during treatment of hyperlipoproteinaemia.", "contents": "On the rise in low density and high density lipoproteins in response to the treatment of hypertriglyceridaemias in type IV and type V hyperlipoproteinaemias. In Type V hyperlipoproteinaemia the concentration of LDL and HDL cholesterol is low. When the hypertriglyceridaemia is normalized, either by diet or micotinic acid, both LDL and HDL increase. In Type IV hyperlipoproteinaemia both LDL and HDL cholesterol decrease with increasing VLDL levels. During treatment of Type IV the change in LDL cholesterol is linearly related to the pretreatment LDL concentration so that higher LDL levels will fall and the lower will rise. HDL levels will also rise. The fall in VLDL during treatment is rapid and the rise in LDL also occurs rapidly indicating a relationship between these two reciprocal changes. HDL cholesterol, however, however, remains constant some time after VLDL has reached its lowest level and the rise occurs later indicating another mechanism than for LDL. These changes in the three major lipoprotein classes deserve clinical attention. While both the fall in VLDL and the rise in HDL may be benefical from the point of view of atherosclerosis the rise in LDL may be harmful. These is at present no way to evaluate the effect of these complex changes. However, these findings stress the imporance of considering changes in lipoprotein levels and not only in total serum triglycerides and cholesterol during treatment of hyperlipoproteinaemia."}
{"id": "PMID:193527", "title": "Effect of estrogens on the concentration and composition of arterial sterols and steryl esters in male white carneau pigeons.", "content": "The effect of short-term (6 months) administration of conjugated equine estrogen (Premarin) on content and composition of the aortic sterols in male shite Carneau pigeons while they were on a cholesterol-free grain diet was investigated. Estrogen treatment resulted in a 38% increase (P less than 0.05) in free sterol concentration, with a 28.8% concomitant decrease (P less than 0.05) in the percent of cholesteryl esters. The total sterol concentration remained unchanged. This finding suggests that estrogens might influence the synthetic or hydrolytic (or both) processes that control the concentration of cholesteryl  esters in the aorta. Fatty acid composition of steryl esters did not change significantly. The cholesterol content of plasma showed a mild reduction (14%) whereas the triglycerides increased significantly (30%).", "contents": "Effect of estrogens on the concentration and composition of arterial sterols and steryl esters in male white carneau pigeons. The effect of short-term (6 months) administration of conjugated equine estrogen (Premarin) on content and composition of the aortic sterols in male shite Carneau pigeons while they were on a cholesterol-free grain diet was investigated. Estrogen treatment resulted in a 38% increase (P less than 0.05) in free sterol concentration, with a 28.8% concomitant decrease (P less than 0.05) in the percent of cholesteryl esters. The total sterol concentration remained unchanged. This finding suggests that estrogens might influence the synthetic or hydrolytic (or both) processes that control the concentration of cholesteryl  esters in the aorta. Fatty acid composition of steryl esters did not change significantly. The cholesterol content of plasma showed a mild reduction (14%) whereas the triglycerides increased significantly (30%)."}
{"id": "PMID:193528", "title": "Hypertension-accelerated atherogenesis in cholesterol-fed rabbits.", "content": "Entry of 125I-labelled low density lipoprotein ([125I]LDL) into the aortic intima was studied over 6 hours in normotenisve and hypertensive rabbits fed a 1% cholesterol diet for 9 and 4 weeks respectively. Studies were also made in hypertensive and normotensive cholesterol-fed rabbits in which blood pressure was reduced acutely with parenteral hydralazine. In all groups the entry of E1125I]LDL was greatest in the aortic arch and significantly less in both the descending thoracic and abdominal regions. Lipoprotein entry into the aorta of cholesterol-fed rabbits was increased some 10-fold over the corresponding value previously found in rabbits fed a normal diet [1]. This increase was due to increased vascular permeability as well as to increased plasma LDL concentration. The hypertensive cholesterol-fed rabbits did not show significantly greater entry of [125I]LDL than the normotensive cholesterol-fed rabbits. Comparison of the rate of LDL entry over 6 house and the quanitity of cholesterol accumulated in the aortic segments over the period of cholesterol feeding indicated that lipoprotein fractions other than LDL must contribute singificant amounts of cholesterol to the developing lesion. The finding that LDL entry paralledled accumulation during cholesterol feeding, together with the finding that acute reversal of hypertension did not reduce the entry of [125I] LDL suggest that mechanisms other than increased filtration of plasma low density lipoprotein contribute significantly to the accelerated development of atherosclerosis in hypertension.", "contents": "Hypertension-accelerated atherogenesis in cholesterol-fed rabbits. Entry of 125I-labelled low density lipoprotein ([125I]LDL) into the aortic intima was studied over 6 hours in normotenisve and hypertensive rabbits fed a 1% cholesterol diet for 9 and 4 weeks respectively. Studies were also made in hypertensive and normotensive cholesterol-fed rabbits in which blood pressure was reduced acutely with parenteral hydralazine. In all groups the entry of E1125I]LDL was greatest in the aortic arch and significantly less in both the descending thoracic and abdominal regions. Lipoprotein entry into the aorta of cholesterol-fed rabbits was increased some 10-fold over the corresponding value previously found in rabbits fed a normal diet [1]. This increase was due to increased vascular permeability as well as to increased plasma LDL concentration. The hypertensive cholesterol-fed rabbits did not show significantly greater entry of [125I]LDL than the normotensive cholesterol-fed rabbits. Comparison of the rate of LDL entry over 6 house and the quanitity of cholesterol accumulated in the aortic segments over the period of cholesterol feeding indicated that lipoprotein fractions other than LDL must contribute singificant amounts of cholesterol to the developing lesion. The finding that LDL entry paralledled accumulation during cholesterol feeding, together with the finding that acute reversal of hypertension did not reduce the entry of [125I] LDL suggest that mechanisms other than increased filtration of plasma low density lipoprotein contribute significantly to the accelerated development of atherosclerosis in hypertension."}
{"id": "PMID:193529", "title": "Transplacental acquisition of cytomegalovirus antibody. Observations with two different CMV strains.", "content": "Titrations of complement fixing antibody (c.f.a.) were done in paired sera of 127 women at delivery and cord blood of their babies using two different cytomegalovirus strains both of which had undergone many passages in WI-38 cells, With High strain 74% of the mother and 41% of the babies were negative at the serum dilution 1:4. With Towne strain the incidence of negative was 5% both among the mother and the newborns. Worth of mention is the study of correlation of the titers in the matched pairs of sera according to the strain. With High strain 23 of the babies had c.f.a. titers significantly higher than their mothers and 14 of them were from negative women. This situation could be suggestive of an active placental transfer of IgG globulins. No such disparities were found using Towne strain as antigen. 48 pairs of sera were then tested with both strains by indirect hemagglutination, indirect immunofluorescence and gel precipitin test. Results are discussed in relation to the possible differences in the antigenic composition of the two cytomegalovirus strains.", "contents": "Transplacental acquisition of cytomegalovirus antibody. Observations with two different CMV strains. Titrations of complement fixing antibody (c.f.a.) were done in paired sera of 127 women at delivery and cord blood of their babies using two different cytomegalovirus strains both of which had undergone many passages in WI-38 cells, With High strain 74% of the mother and 41% of the babies were negative at the serum dilution 1:4. With Towne strain the incidence of negative was 5% both among the mother and the newborns. Worth of mention is the study of correlation of the titers in the matched pairs of sera according to the strain. With High strain 23 of the babies had c.f.a. titers significantly higher than their mothers and 14 of them were from negative women. This situation could be suggestive of an active placental transfer of IgG globulins. No such disparities were found using Towne strain as antigen. 48 pairs of sera were then tested with both strains by indirect hemagglutination, indirect immunofluorescence and gel precipitin test. Results are discussed in relation to the possible differences in the antigenic composition of the two cytomegalovirus strains."}
{"id": "PMID:193530", "title": "Complement fixing antibody to varicella-zoster virus in different age groups and after zoster.", "content": "The titer of complement fixing antibody to Varicella-Zoster virus was studied in sera from 215 normal persons living in Padua and its province and from 39 Zoster patients. About 74% of sera from normal persons aged 21-80 years had antibody titers larger than or equal to 1/4. Lower titers were present in the age groups 1-20 years and 81-90 years. Sera from Zoster patients had high titers from the second week following the onset of the rash. They were still comparatively high until the fifth month, sometimes remaining detectable even after a year or more.", "contents": "Complement fixing antibody to varicella-zoster virus in different age groups and after zoster. The titer of complement fixing antibody to Varicella-Zoster virus was studied in sera from 215 normal persons living in Padua and its province and from 39 Zoster patients. About 74% of sera from normal persons aged 21-80 years had antibody titers larger than or equal to 1/4. Lower titers were present in the age groups 1-20 years and 81-90 years. Sera from Zoster patients had high titers from the second week following the onset of the rash. They were still comparatively high until the fifth month, sometimes remaining detectable even after a year or more."}
{"id": "PMID:193531", "title": "Neurobiology of aggressive behavior.", "content": "Causality, neurological mechanisms, and behavioral manifestations may be heterogeneous in different forms of aggressive behavior, but some elements are shared by all forms of violence, including the necessity of sensory inputs, the coding and decoding of information according to acquired frames of reference, and the activation of pre-established patterns of response. Understanding and prevention of violence requires a simultaneous study of its social, cultural, and economic aspects, at parity with an investigation of its neurological mechanisms. Part of the latter information may be obtained through animal experimentation, preferably in non-human primates. Feline predatory behavior has no equivalent in man, and therefore its hypothalamic representation probably does not exist in the human brain. Codes of information, frames of reference for sensory perception, axis to evaluate threats, and formulas for aggressive performance are not established genetically but must be learned individually. We are born with the capacity to learn aggressive behavior, but not with established patterns of violence. Mechanisms for fighting which are acquired by individual experience may be triggered in a similar way by sensory cues, volition, and by electrical stimulation of specific cerebral areas. In monkeys, aggressive responses may be modified by changing the hierarchical position of the stimulated animal, indicating the physiological quality of the neurological mechanisms electrically activated.", "contents": "Neurobiology of aggressive behavior. Causality, neurological mechanisms, and behavioral manifestations may be heterogeneous in different forms of aggressive behavior, but some elements are shared by all forms of violence, including the necessity of sensory inputs, the coding and decoding of information according to acquired frames of reference, and the activation of pre-established patterns of response. Understanding and prevention of violence requires a simultaneous study of its social, cultural, and economic aspects, at parity with an investigation of its neurological mechanisms. Part of the latter information may be obtained through animal experimentation, preferably in non-human primates. Feline predatory behavior has no equivalent in man, and therefore its hypothalamic representation probably does not exist in the human brain. Codes of information, frames of reference for sensory perception, axis to evaluate threats, and formulas for aggressive performance are not established genetically but must be learned individually. We are born with the capacity to learn aggressive behavior, but not with established patterns of violence. Mechanisms for fighting which are acquired by individual experience may be triggered in a similar way by sensory cues, volition, and by electrical stimulation of specific cerebral areas. In monkeys, aggressive responses may be modified by changing the hierarchical position of the stimulated animal, indicating the physiological quality of the neurological mechanisms electrically activated."}
{"id": "PMID:193541", "title": "[Peripheral nerve disease associated with acute renal failure due to bromate poisoning].", "content": "A case of 21 year old male with neuropathy caused by renal insufficiency was present. He had taken bromate (mixed powder of potassium bromate and sodium bromate) for the purpose of suicide and suffered from acute renal insufficiency and hard of hearing. Renal dysfunction improved gradually by peritoneal dialysis and hemodialysis. However, on the 32th day after the onset, burning pain appeared in the bilateral feets. Following this, he began to complain of the disturbances of superficial and deep sensory below the ankle jerks and the weakness of his toes. Considering the clinical features, we supposed that the disturbance of the peripheral nerve was caused by uremia due to taking bromate. N. suralis was biopsied on the 80th day after the onset and examined electron microscopically. Electroscopical findings was as follows. Degeneration of the Schwann cells and irregularity or destruction of the myelin sheaths were observed. The axoplasm of the myelinated nerve fiber were relatively preserved as compared with the changes of the myelin sheaths. In the unmyelinated nerve fibers, cavity formations were observed. The findings of regeneration were not observed. From the electron microscopical findings, we speculate that the changes of the Schwann cells and the myelin sheaths are primary resulting from the disturbance of the metabolism of the Schwann cells. We speculate that anemia and hypoproteinemia caused by bromate disturbed regeneration.", "contents": "[Peripheral nerve disease associated with acute renal failure due to bromate poisoning]. A case of 21 year old male with neuropathy caused by renal insufficiency was present. He had taken bromate (mixed powder of potassium bromate and sodium bromate) for the purpose of suicide and suffered from acute renal insufficiency and hard of hearing. Renal dysfunction improved gradually by peritoneal dialysis and hemodialysis. However, on the 32th day after the onset, burning pain appeared in the bilateral feets. Following this, he began to complain of the disturbances of superficial and deep sensory below the ankle jerks and the weakness of his toes. Considering the clinical features, we supposed that the disturbance of the peripheral nerve was caused by uremia due to taking bromate. N. suralis was biopsied on the 80th day after the onset and examined electron microscopically. Electroscopical findings was as follows. Degeneration of the Schwann cells and irregularity or destruction of the myelin sheaths were observed. The axoplasm of the myelinated nerve fiber were relatively preserved as compared with the changes of the myelin sheaths. In the unmyelinated nerve fibers, cavity formations were observed. The findings of regeneration were not observed. From the electron microscopical findings, we speculate that the changes of the Schwann cells and the myelin sheaths are primary resulting from the disturbance of the metabolism of the Schwann cells. We speculate that anemia and hypoproteinemia caused by bromate disturbed regeneration."}
{"id": "PMID:193547", "title": "Immunological mechanisms in metastatic spread and the antimetastatic effects of C. parvum.", "content": "The effects of the host's immune response on metastatic spread was investigated by observing the numbers of pulmonary metastases that developed from an s.c. implant of the Lewis lung carcinoma in C57BL mice in which different cell populations had been suppressed. Macrophage function was impaired by treatment with silica (Si), cortisone acetate (CA), or trypan blue (TB). T-cell function was depressed by adult thymectomy and sublethal irradiation, or by treatment with antilymphocyte serum (ALS). Metastasis was significantly increased and phagocytic activity decreased by Si and CA, but were unaffected by TB. Thymectomy and irradiation had no effect on metastases, whereas ALS when given before, but not after tumour growth, reduced their number. The antimetastatic action of the immunopotentiating agent C. parvum was investigated in these immunologically impaired mice. It was unaffected by Si, CA or TB. However, the inhibiting effect of these agents on phagocytic activity was overcome by treatment with C. parvum. Its antimetastatic action was unaffected in mice which had been thymectomized and irradiated, but could be abrogated by ALS. However, ALS was only able to prevent this activity if given before tumour growth; it was ineffective if given after tumour growth. This study showed that metastatic spread was inversely related to phagocytic activity. The antimetastatic effect of C. parvum appears to be mediated through macrophages in concert with a subpopulation of T lymphocytes, which were considered to be necessary in the sensitization arm of the response as opposed to the effector arm of this response.", "contents": "Immunological mechanisms in metastatic spread and the antimetastatic effects of C. parvum. The effects of the host's immune response on metastatic spread was investigated by observing the numbers of pulmonary metastases that developed from an s.c. implant of the Lewis lung carcinoma in C57BL mice in which different cell populations had been suppressed. Macrophage function was impaired by treatment with silica (Si), cortisone acetate (CA), or trypan blue (TB). T-cell function was depressed by adult thymectomy and sublethal irradiation, or by treatment with antilymphocyte serum (ALS). Metastasis was significantly increased and phagocytic activity decreased by Si and CA, but were unaffected by TB. Thymectomy and irradiation had no effect on metastases, whereas ALS when given before, but not after tumour growth, reduced their number. The antimetastatic action of the immunopotentiating agent C. parvum was investigated in these immunologically impaired mice. It was unaffected by Si, CA or TB. However, the inhibiting effect of these agents on phagocytic activity was overcome by treatment with C. parvum. Its antimetastatic action was unaffected in mice which had been thymectomized and irradiated, but could be abrogated by ALS. However, ALS was only able to prevent this activity if given before tumour growth; it was ineffective if given after tumour growth. This study showed that metastatic spread was inversely related to phagocytic activity. The antimetastatic effect of C. parvum appears to be mediated through macrophages in concert with a subpopulation of T lymphocytes, which were considered to be necessary in the sensitization arm of the response as opposed to the effector arm of this response."}
{"id": "PMID:193548", "title": "Possible transformation of nasopharyngeal epithelial cells in culture with Epstein-Barr virus from B95-8 cells.", "content": "Explants of fresh biopsy specimens from non-neoplastic nasopharyngeal (NP) mucosa, nasopharyngeal carcinoma (NPC), other tumours (OT) of the head and neck and freshly removed tonsils were treated with an Epstein-Barr virus (EBV) preparation from B95-8 cells and cultured. The mainly epitheloid outgrowths from these infected explants were then compared with those from their respective uninfected controls at 14 days. Growth stimulation occurred with a significantly higher frequency, and the degree of stimulation was generally higher with the infected NP explants than those of the similarly infected explants of other origins. Furthermore, after treatment with the virus preparation, several of the outgrowths from the NP explants showed growth characteristics and cellular morphology typical of those of transformed cells. Light microscopy has shown the changed NP cells to have epithelial characteristics. This is now being verified by electron microscopy, which has so far shown the presence of keratin fibrils and desmosomes in one specimen examined. They are also being examined for the presence of EBV-DNA and EBNA, and other features of transformation, including malignant tendency, by passage through athymic nude mice.", "contents": "Possible transformation of nasopharyngeal epithelial cells in culture with Epstein-Barr virus from B95-8 cells. Explants of fresh biopsy specimens from non-neoplastic nasopharyngeal (NP) mucosa, nasopharyngeal carcinoma (NPC), other tumours (OT) of the head and neck and freshly removed tonsils were treated with an Epstein-Barr virus (EBV) preparation from B95-8 cells and cultured. The mainly epitheloid outgrowths from these infected explants were then compared with those from their respective uninfected controls at 14 days. Growth stimulation occurred with a significantly higher frequency, and the degree of stimulation was generally higher with the infected NP explants than those of the similarly infected explants of other origins. Furthermore, after treatment with the virus preparation, several of the outgrowths from the NP explants showed growth characteristics and cellular morphology typical of those of transformed cells. Light microscopy has shown the changed NP cells to have epithelial characteristics. This is now being verified by electron microscopy, which has so far shown the presence of keratin fibrils and desmosomes in one specimen examined. They are also being examined for the presence of EBV-DNA and EBNA, and other features of transformation, including malignant tendency, by passage through athymic nude mice."}
{"id": "PMID:193549", "title": "Ultrastructural changes of intercellular junctions in rat ascites hepatoma cells with calcium depletion.", "content": "To analyse the effect of ethylenediamine tetraacetate (EDTA) on tumour cell adhesiveness, fine structure of intercellular junctions of rat ascites hepatoma cells AH136B and AH7974 (both forming cell islands in vivo) was first compared. The close contact of the apical portion of both cell islands was composed of tight junctions with a narrow gap. The close contact of the inner portion of AH136B cell islands was largely by simple apposition, while that of AH7974 cell islands had many intermediate junctions and desmosomes. Treatment with EDTA (2 mM) induced morphological alteration of simple apposition, intermediate junctions and desmosomes, but tight junctions remained intact. The effect of EDTA on such junctional complexes seemed to be partially reversible on readministration of Ca ions. Changes in desmosomes, as confirmed on AH7974 cells, were initiated by disappearance of the central disc of electron-dense materials, followed by marked opening of intercellular space and disappearance of endoplasmic laminar plaque. These results suggest that Ca ions may be concerned with maintaining the integrity of junctional complexes other than tight junctions.", "contents": "Ultrastructural changes of intercellular junctions in rat ascites hepatoma cells with calcium depletion. To analyse the effect of ethylenediamine tetraacetate (EDTA) on tumour cell adhesiveness, fine structure of intercellular junctions of rat ascites hepatoma cells AH136B and AH7974 (both forming cell islands in vivo) was first compared. The close contact of the apical portion of both cell islands was composed of tight junctions with a narrow gap. The close contact of the inner portion of AH136B cell islands was largely by simple apposition, while that of AH7974 cell islands had many intermediate junctions and desmosomes. Treatment with EDTA (2 mM) induced morphological alteration of simple apposition, intermediate junctions and desmosomes, but tight junctions remained intact. The effect of EDTA on such junctional complexes seemed to be partially reversible on readministration of Ca ions. Changes in desmosomes, as confirmed on AH7974 cells, were initiated by disappearance of the central disc of electron-dense materials, followed by marked opening of intercellular space and disappearance of endoplasmic laminar plaque. These results suggest that Ca ions may be concerned with maintaining the integrity of junctional complexes other than tight junctions."}
{"id": "PMID:193550", "title": "Experimental infection of rabbits with the virus of infectious bovine rhinotracheitis.", "content": "Adult and newborn rabbits were infected with the LA strain of infectious bovine rhinotracheitis virus. Adult rabbits developed only mild, self-limiting conjunctivitis, but had microscopic inflammatory foci in the liver and adrenal glands. Newborn rabbits developed a severe, sometimes fatal, generalized infection with focal and diffuse necrosis of the liver and adrenal glands.", "contents": "Experimental infection of rabbits with the virus of infectious bovine rhinotracheitis. Adult and newborn rabbits were infected with the LA strain of infectious bovine rhinotracheitis virus. Adult rabbits developed only mild, self-limiting conjunctivitis, but had microscopic inflammatory foci in the liver and adrenal glands. Newborn rabbits developed a severe, sometimes fatal, generalized infection with focal and diffuse necrosis of the liver and adrenal glands."}
{"id": "PMID:193551", "title": "Interspecies homology of RNA tumor virus proteins.", "content": "We report the application of a highly sensitive column chromatographic technique to the comparison of tryptic peptide maps of some RNA tumor virus proteins. By combining microbore ion-exchange chromatography with a sensitive fluorescent assay using o-phthalaldehyde, we obtained high-resolution peptide maps starting with only microgram amounts of protein. Our discovery of coincident peptides from the 15,000 and 30,000 molecular weight proteins from murine and feline leukemia viruses supports serological evidence for interspecies antigenic determinants; coincident peptides were also found for the 10,000 molecular weight proteins from these viruses, although immunochemical data did not reveal interspecies determinants. The relatively large number of coeluting peptides found in the 15,000 and 10,000 molecular weight proteins is strong evidence for the existence of homology.", "contents": "Interspecies homology of RNA tumor virus proteins. We report the application of a highly sensitive column chromatographic technique to the comparison of tryptic peptide maps of some RNA tumor virus proteins. By combining microbore ion-exchange chromatography with a sensitive fluorescent assay using o-phthalaldehyde, we obtained high-resolution peptide maps starting with only microgram amounts of protein. Our discovery of coincident peptides from the 15,000 and 30,000 molecular weight proteins from murine and feline leukemia viruses supports serological evidence for interspecies antigenic determinants; coincident peptides were also found for the 10,000 molecular weight proteins from these viruses, although immunochemical data did not reveal interspecies determinants. The relatively large number of coeluting peptides found in the 15,000 and 10,000 molecular weight proteins is strong evidence for the existence of homology."}
{"id": "PMID:193552", "title": "Studies on conformation of soluble and immobilized enzymes using differential scanning calorimetry. 1. Thermal stability of nicotinamide adenine dinucleotide dependent dehydrogenases.", "content": "The technique of differential scanning calorimetry (DSC) has been applied to the study of temperature-induced irreversible denturation and thus to the heat stability of soluble and Sepharose-bound liver alcohol dehydrogenase (LADH, EC 1.1.1.1) and lactate dehydrogenase (LDH, EC 1.1.1.27) in the presence of various coenzymes or coenzyme fragments. The transition temperature (Ttr) of 82.5 degrees C obtained for soluble LADH was increased by 12.5 degrees C in the presence of a saturating concentration of NACH. In the presence of NAD+, Ttr increased by 8.5 degrees C, whereas ADP-ribose and AMP caused an increase in Ttr of only 2 and 1 degree C, respectively. The Ttr of 85.5 degrees C obtained for Sepharose-bound LADH was increased by about 12 degrees C after the addition of free NADH. However, when the enzyme was immobilized simultaneously with a NADH analogue (which also binds to the matrix), a broad endotherm with a Ttr of 91.5 degrees C was obtained, indicating the presence of immobilized enzyme molecules both with, and without, associated NADH. Corresponding increases in heat stability were observed for LDH in solution in the presence of NADH, NAD+, and AMP, leading to increases in Ttr from 72 to 79.5 and 74 and 73 degrees C, respectively. The addition of pyruvate and NAD+ to the enzyme to form an abortive ternary complex led to the same stabilization as that observed with NADH, attendant with a large increase in the enthalpy of transition, deltaHtr. In these studies the technique of DSC was utilized because it is applicable both to soluble and immobilized enzymes and (1) provides rapid information about Ttr and thus thermal stability of enzymes, (2) different energetic states of an enzyme molecule can be identified, and (3) an overall picture of the thermal process is rapidly obtained.", "contents": "Studies on conformation of soluble and immobilized enzymes using differential scanning calorimetry. 1. Thermal stability of nicotinamide adenine dinucleotide dependent dehydrogenases. The technique of differential scanning calorimetry (DSC) has been applied to the study of temperature-induced irreversible denturation and thus to the heat stability of soluble and Sepharose-bound liver alcohol dehydrogenase (LADH, EC 1.1.1.1) and lactate dehydrogenase (LDH, EC 1.1.1.27) in the presence of various coenzymes or coenzyme fragments. The transition temperature (Ttr) of 82.5 degrees C obtained for soluble LADH was increased by 12.5 degrees C in the presence of a saturating concentration of NACH. In the presence of NAD+, Ttr increased by 8.5 degrees C, whereas ADP-ribose and AMP caused an increase in Ttr of only 2 and 1 degree C, respectively. The Ttr of 85.5 degrees C obtained for Sepharose-bound LADH was increased by about 12 degrees C after the addition of free NADH. However, when the enzyme was immobilized simultaneously with a NADH analogue (which also binds to the matrix), a broad endotherm with a Ttr of 91.5 degrees C was obtained, indicating the presence of immobilized enzyme molecules both with, and without, associated NADH. Corresponding increases in heat stability were observed for LDH in solution in the presence of NADH, NAD+, and AMP, leading to increases in Ttr from 72 to 79.5 and 74 and 73 degrees C, respectively. The addition of pyruvate and NAD+ to the enzyme to form an abortive ternary complex led to the same stabilization as that observed with NADH, attendant with a large increase in the enthalpy of transition, deltaHtr. In these studies the technique of DSC was utilized because it is applicable both to soluble and immobilized enzymes and (1) provides rapid information about Ttr and thus thermal stability of enzymes, (2) different energetic states of an enzyme molecule can be identified, and (3) an overall picture of the thermal process is rapidly obtained."}
{"id": "PMID:193553", "title": "Iodinated neurohypophyseal hormones as potential ligands for receptor binding and intermediates in synthesis of tritiated hormones.", "content": "[3-Iodo-Tyr2]oxytocin (MIOT), [3,5-diiodo-Tyr2]oxytocin (DIOT), [3-iodo-Tyr2,Lys8]vasopressin (MILVP), [3,5-diiodo-Tyr2,Lys8]vasopressin (DILVP), [3-iodo-Tyr2,Arg8]vasopressin (MIAVP), and [3,5-diiodo-Tyr2,Arg8]vasopressin (DIAVP) were synthesized by iodination of the respective hormones, pruified, and characterized. All the monoiodo hormones had to be freshly prepared prior to bioassays, since on storage they gave rise to hormonal-like biological activity. The biological activities of these iodo analogues were measured in an adenylate cyclase assay employing neurohypophyseal hormone (NHH) sensitive bovine renal medullary membranes, and/or the rat oxytocic assay. In the cyclase assay, DIOT, DILVP, and DIAVP were inactive as agonists or antagonists. MIOT shows no agonistic activity in the renal cyclase system and uterus, but is a weak reversible inhibitor of oxytocin (OT) in both systems. When MIOT (10(-4) M) was preincubated with renal membranes for 10 min at 37 degrees C before addition of OT, it behaved as a noncompetitive inhibitor of NHH-stimulated adenylate cyclase. MILVP and MIAVP appear to be partial agonists with Km (half maximal response) 3 X 10(-6) and 3 X 10(-7) M, respectively, as determined in the cyclase assay. Upon preincubation with renal medullary membranes, MILVP (10(-6) M) behaves as a more potent noncompetitive inhibitor of OT than MIOT. Accordingly, iodo derivatives of NHH do not exhibit sufficient affinity to serve an specific ligands to measure OT, LVP, or AVP receptors in the uterus and kidney. Study of the specificity of inhibition produced by MIOT revealed that this analogue does not act selectively upon NHH receptors. Thus, MIOT modified adenylate cyclase systems which do not have NHH receptors, e.g., the PTH-sensitive adenylate cyclase in bovine renal cortex and the glucagon-sensitive adenylate cyclase in rat liver. DIOT, DILVP, and DIAVP were subjected to catalytic tritiation (employing carrier free tritium) and were converted to [3H]OT (25, 31, and 25 Ci/mmol), [3H]LVP (26 and 23 Ci/mmol), and [3H]AVP (17 Ci/mmol), respectively. These tritiated ligands have been successfully used to measure NHH receptor sites both in kidney and uterine membranes as described in other studies.", "contents": "Iodinated neurohypophyseal hormones as potential ligands for receptor binding and intermediates in synthesis of tritiated hormones. [3-Iodo-Tyr2]oxytocin (MIOT), [3,5-diiodo-Tyr2]oxytocin (DIOT), [3-iodo-Tyr2,Lys8]vasopressin (MILVP), [3,5-diiodo-Tyr2,Lys8]vasopressin (DILVP), [3-iodo-Tyr2,Arg8]vasopressin (MIAVP), and [3,5-diiodo-Tyr2,Arg8]vasopressin (DIAVP) were synthesized by iodination of the respective hormones, pruified, and characterized. All the monoiodo hormones had to be freshly prepared prior to bioassays, since on storage they gave rise to hormonal-like biological activity. The biological activities of these iodo analogues were measured in an adenylate cyclase assay employing neurohypophyseal hormone (NHH) sensitive bovine renal medullary membranes, and/or the rat oxytocic assay. In the cyclase assay, DIOT, DILVP, and DIAVP were inactive as agonists or antagonists. MIOT shows no agonistic activity in the renal cyclase system and uterus, but is a weak reversible inhibitor of oxytocin (OT) in both systems. When MIOT (10(-4) M) was preincubated with renal membranes for 10 min at 37 degrees C before addition of OT, it behaved as a noncompetitive inhibitor of NHH-stimulated adenylate cyclase. MILVP and MIAVP appear to be partial agonists with Km (half maximal response) 3 X 10(-6) and 3 X 10(-7) M, respectively, as determined in the cyclase assay. Upon preincubation with renal medullary membranes, MILVP (10(-6) M) behaves as a more potent noncompetitive inhibitor of OT than MIOT. Accordingly, iodo derivatives of NHH do not exhibit sufficient affinity to serve an specific ligands to measure OT, LVP, or AVP receptors in the uterus and kidney. Study of the specificity of inhibition produced by MIOT revealed that this analogue does not act selectively upon NHH receptors. Thus, MIOT modified adenylate cyclase systems which do not have NHH receptors, e.g., the PTH-sensitive adenylate cyclase in bovine renal cortex and the glucagon-sensitive adenylate cyclase in rat liver. DIOT, DILVP, and DIAVP were subjected to catalytic tritiation (employing carrier free tritium) and were converted to [3H]OT (25, 31, and 25 Ci/mmol), [3H]LVP (26 and 23 Ci/mmol), and [3H]AVP (17 Ci/mmol), respectively. These tritiated ligands have been successfully used to measure NHH receptor sites both in kidney and uterine membranes as described in other studies."}
{"id": "PMID:193554", "title": "Physical properties of the dimyristoylphosphatidylcholine vesicle and of complexes formed by its interaction with apolipoprotein C-III.", "content": "The structure of a single bilayer vesicle of dimyristoylphosphatidylcholine has been characterized by sedimentation, densimetry, and light-scattering measurements. The molecular weight, partial specific volume, Stokes radius, and degree by hydration were found to be 2.68 X 10(6), 0.972 cm3/g, 125 A, and 0.86 g/g, respectively. From these quantities, a spherically symmetrical model has been derived that features a phospholipid bilayer 35.5 A thick and a hydration shell 9.3 A thick. This particle was shown to bind apolipoprotein C-III (apoC-III) up to 0.08 g/g without loss of its original vesicular structure. At protein-lipid ratios in excess of 0.08 g/g, sedimentation, gel chromatography, and light-scattering measurement indicated a dramatic decrease in Stokes radius and molecular weight. The sedimentation data showed these parameters to become constant at protein-lipid ratios in excess of 0.25 g/g. In this region, the Stokes radius and molecular weight were found to be approximately 80 A and 442 000, respectively. Within the constraints of these values and other data, several models for this complex are discussed.", "contents": "Physical properties of the dimyristoylphosphatidylcholine vesicle and of complexes formed by its interaction with apolipoprotein C-III. The structure of a single bilayer vesicle of dimyristoylphosphatidylcholine has been characterized by sedimentation, densimetry, and light-scattering measurements. The molecular weight, partial specific volume, Stokes radius, and degree by hydration were found to be 2.68 X 10(6), 0.972 cm3/g, 125 A, and 0.86 g/g, respectively. From these quantities, a spherically symmetrical model has been derived that features a phospholipid bilayer 35.5 A thick and a hydration shell 9.3 A thick. This particle was shown to bind apolipoprotein C-III (apoC-III) up to 0.08 g/g without loss of its original vesicular structure. At protein-lipid ratios in excess of 0.08 g/g, sedimentation, gel chromatography, and light-scattering measurement indicated a dramatic decrease in Stokes radius and molecular weight. The sedimentation data showed these parameters to become constant at protein-lipid ratios in excess of 0.25 g/g. In this region, the Stokes radius and molecular weight were found to be approximately 80 A and 442 000, respectively. Within the constraints of these values and other data, several models for this complex are discussed."}
{"id": "PMID:193555", "title": "Characterization of baboon plasma high-density lipoproteins and of their major apoproteins.", "content": "Baboon high-density lipoproteins (HDL) were isolated by preparative ultracentrifugation between d = 1.063 and 1.215 g/mL. The HDL contains 48.8% protein and a lipid distribution similar to human HDL. The phospholipid distribution shows a low sphingomyelin value (5.9%), and the fatty acid composition of HDL is comparable to the human data except for the 18:1/18:2 ratio as a result of a higher 18:1 content in the CE and a lower 18:2 concentration in the PL. The major HDL apoproteins isolated on diethylaminoethyl-cellulose had a mobility on sodium dodecyl sulfate--polyacrylamide gel electrophoresis and a molecular weight and an amino acid composition similar to human apoA-I. However, the amino acid sequence of the first 30 residues of baboon apoA-I differed from the human apoprotein in residues 15 and 21. Treatment of apoA-I with carboxypeptidase A indicated a carboxyl-terminal sequence of Leu-Ser-Thr-Gln. Baboon apoHDL contained monomeric apoA-II with the mobility of monomeric human apoA-II and a molecular weight of 8500. The amino acid composition differed from the human apoA-II by the presence of arginine and by the absence of half-cystine and isoleucine. The circular dichroic spectra of apoA-I and apoA-II demonstrated a higher helicity compared to the human apoproteins. Recombination studies by microcalorimetry of apoHDL with dimyristoylphosphatidylcholine (DMPC) indicated similarities in the thermodynamic binding properties of the HDL apoproteins from man and baboon. The maximal-binding enthalpies of DMPC to apoHDL, apoA-I, and apoA-II were lower for the baboon than for the human apoprotein.", "contents": "Characterization of baboon plasma high-density lipoproteins and of their major apoproteins. Baboon high-density lipoproteins (HDL) were isolated by preparative ultracentrifugation between d = 1.063 and 1.215 g/mL. The HDL contains 48.8% protein and a lipid distribution similar to human HDL. The phospholipid distribution shows a low sphingomyelin value (5.9%), and the fatty acid composition of HDL is comparable to the human data except for the 18:1/18:2 ratio as a result of a higher 18:1 content in the CE and a lower 18:2 concentration in the PL. The major HDL apoproteins isolated on diethylaminoethyl-cellulose had a mobility on sodium dodecyl sulfate--polyacrylamide gel electrophoresis and a molecular weight and an amino acid composition similar to human apoA-I. However, the amino acid sequence of the first 30 residues of baboon apoA-I differed from the human apoprotein in residues 15 and 21. Treatment of apoA-I with carboxypeptidase A indicated a carboxyl-terminal sequence of Leu-Ser-Thr-Gln. Baboon apoHDL contained monomeric apoA-II with the mobility of monomeric human apoA-II and a molecular weight of 8500. The amino acid composition differed from the human apoA-II by the presence of arginine and by the absence of half-cystine and isoleucine. The circular dichroic spectra of apoA-I and apoA-II demonstrated a higher helicity compared to the human apoproteins. Recombination studies by microcalorimetry of apoHDL with dimyristoylphosphatidylcholine (DMPC) indicated similarities in the thermodynamic binding properties of the HDL apoproteins from man and baboon. The maximal-binding enthalpies of DMPC to apoHDL, apoA-I, and apoA-II were lower for the baboon than for the human apoprotein."}
{"id": "PMID:193556", "title": "Bovine liver fructokinase: purification and kinetic properties.", "content": "Fructokinase from beef liver has been purified 2300-fold by acid and heat treatment, ammonium sulfate fractionation, and chromatography on Sephadex G-100, DEAE- and CM-cellulose. The purified enzyme is homogeneous by all criteria examined, has a molecular weight of 56 000, and is a dimer of equal molecular weight subunits. The isoelectric point is 5.7. The Michaelis constant for activation by K+ is 15 mM, and the enzyme is also activated by Na+, Rb+, Cs+, NH4+, and TL+. The kinetic mechanism has been determined at pH 7.0, 25 degrees C. The initial velocity, product, and dead-end inhibition patterns for CrATP, CrADP, and 1-deoxy-D-fructose are consistent with a random kinetic mechanism with the formation of two dead-end complexes. Substrates for fructokinase include: D-fructose, L-sorbose, D-tagatose, D-psicose, D-xylulose, L-ribulose, D-sedoheptulose, L-galactoheptulose, D-mannoheptulose, 5-keto-D-fructose, D-ribose, 2,5-anhydro-D-mannitol, 2,5-anhydro-D-glucitol, 2,5-anhydro-D-mannose, 2,5-anhydro-D-lyxito.l, and D-ribono-gamma-lactone. 5-Thio-D-fructose was not a substate, but was a competitive inhibitor vs. D-fructose. Thus the minimum molecular for substrate activity seems to be (2R)-2-hydroxy-methyl-3,4-dihydroxytetrahydrofuran. The configuration of the substituents at carbons 3, 4, and 5 appears not to be critical, but the hydroxymethyl group must have the configuration corresponding to beta-D-(or alpha-L-) keto sugars. The anomeric hydroxyl on carbon 2 is not required (although it contributes to binding), and a wide variety of groups may be present at carbon 5.", "contents": "Bovine liver fructokinase: purification and kinetic properties. Fructokinase from beef liver has been purified 2300-fold by acid and heat treatment, ammonium sulfate fractionation, and chromatography on Sephadex G-100, DEAE- and CM-cellulose. The purified enzyme is homogeneous by all criteria examined, has a molecular weight of 56 000, and is a dimer of equal molecular weight subunits. The isoelectric point is 5.7. The Michaelis constant for activation by K+ is 15 mM, and the enzyme is also activated by Na+, Rb+, Cs+, NH4+, and TL+. The kinetic mechanism has been determined at pH 7.0, 25 degrees C. The initial velocity, product, and dead-end inhibition patterns for CrATP, CrADP, and 1-deoxy-D-fructose are consistent with a random kinetic mechanism with the formation of two dead-end complexes. Substrates for fructokinase include: D-fructose, L-sorbose, D-tagatose, D-psicose, D-xylulose, L-ribulose, D-sedoheptulose, L-galactoheptulose, D-mannoheptulose, 5-keto-D-fructose, D-ribose, 2,5-anhydro-D-mannitol, 2,5-anhydro-D-glucitol, 2,5-anhydro-D-mannose, 2,5-anhydro-D-lyxito.l, and D-ribono-gamma-lactone. 5-Thio-D-fructose was not a substate, but was a competitive inhibitor vs. D-fructose. Thus the minimum molecular for substrate activity seems to be (2R)-2-hydroxy-methyl-3,4-dihydroxytetrahydrofuran. The configuration of the substituents at carbons 3, 4, and 5 appears not to be critical, but the hydroxymethyl group must have the configuration corresponding to beta-D-(or alpha-L-) keto sugars. The anomeric hydroxyl on carbon 2 is not required (although it contributes to binding), and a wide variety of groups may be present at carbon 5."}
{"id": "PMID:193557", "title": "Enzymic formation of glycolate in Chromatium. Role of superoxide radical in a transketolase-type mechanism.", "content": "Chromatophores prepared from Chromatium exhibit a light-dependent O2 uptake in the presence of reduced 2,6-dichlorophenolindophenol, the maximum rate observed being 10.8 micronmol (mg of Bchl)-1 h-1 (air-saturated condition). As it was found that the uptake of O2 was markedly inhibited by superoxide dismutase, it is suggested that molecular oxygen is subject to light-dependent monovalent reduction, resulting in the formation of the superoxide anion radical (O2-). By coupling baker's yeast transketolase with illuminated chromatophore preparations, it was demonstrated that [U-14C]-fructose 6-phosphate (6-P) is oxidatively split to produce glycolate, and that the reaction was markedly inhibited by superoxide dismutase and less strongly by catalase. A coupled system containing yeast transketolase and xanthine plus xanthine oxidase showed a similar oxidative formation of glycolate from [U-14C] fructose 6-P. It is thus suggested that photogenerated O2- serves as an oxidant in the transketolase-catalyzed formation of glycolate from the alpha, beta-dihydroxyethyl (C2) thiamine pyrophosphate complex, whereas H2O2 is not an efficient oxidant. The rate of glycolate formation in vitro utilizing O2- does not account for the in vivo rate of glycolate photosynthesis in Chromatium cells exposed to an O2 atmosphere (10 micronmol (mg of Bchl)-1 h-1). However, the enhancement of glycolate formation by the autoxidizable electron acceptor methyl viologen in Chromatium cells in O2, as well as the strong suppression by 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron), an O2- scavenger, suggest that O2- is involved in the light-dependent formation of glycolate in vivo.", "contents": "Enzymic formation of glycolate in Chromatium. Role of superoxide radical in a transketolase-type mechanism. Chromatophores prepared from Chromatium exhibit a light-dependent O2 uptake in the presence of reduced 2,6-dichlorophenolindophenol, the maximum rate observed being 10.8 micronmol (mg of Bchl)-1 h-1 (air-saturated condition). As it was found that the uptake of O2 was markedly inhibited by superoxide dismutase, it is suggested that molecular oxygen is subject to light-dependent monovalent reduction, resulting in the formation of the superoxide anion radical (O2-). By coupling baker's yeast transketolase with illuminated chromatophore preparations, it was demonstrated that [U-14C]-fructose 6-phosphate (6-P) is oxidatively split to produce glycolate, and that the reaction was markedly inhibited by superoxide dismutase and less strongly by catalase. A coupled system containing yeast transketolase and xanthine plus xanthine oxidase showed a similar oxidative formation of glycolate from [U-14C] fructose 6-P. It is thus suggested that photogenerated O2- serves as an oxidant in the transketolase-catalyzed formation of glycolate from the alpha, beta-dihydroxyethyl (C2) thiamine pyrophosphate complex, whereas H2O2 is not an efficient oxidant. The rate of glycolate formation in vitro utilizing O2- does not account for the in vivo rate of glycolate photosynthesis in Chromatium cells exposed to an O2 atmosphere (10 micronmol (mg of Bchl)-1 h-1). However, the enhancement of glycolate formation by the autoxidizable electron acceptor methyl viologen in Chromatium cells in O2, as well as the strong suppression by 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron), an O2- scavenger, suggest that O2- is involved in the light-dependent formation of glycolate in vivo."}
{"id": "PMID:193558", "title": "Isolation and characterization of nonhistone chromosomal protein C-14 which stimulates RNA synthesis.", "content": "The nonhistone chromatin protein, C-14, was extracted from chromatin of Novikoff hepatoma ascites cells and isolated in high purity as shown by its migration as a single dense spot on two-dimensional polyacrylamide gels. Its mobility on sodium dodecyl sulfate gels is consistent with a molecular weight of approximately 70 000. The amino acid composition shows that protein C-14 has an acidic:basic amino acid ratio of 1.8. Its amino terminal amino acid is lysine. Protein C-14 stimulated the incorporation of [3H]UMP into RNA by approximately 30% when added to naked DNA and homologous RNA polymerase I. A 30% stimulation of [3H]UMP incorporation into RNA was also found when protein C-14 was added to an E. coli RNA polymerase system containing either E. coli or Novikoff hepatoma DNA.", "contents": "Isolation and characterization of nonhistone chromosomal protein C-14 which stimulates RNA synthesis. The nonhistone chromatin protein, C-14, was extracted from chromatin of Novikoff hepatoma ascites cells and isolated in high purity as shown by its migration as a single dense spot on two-dimensional polyacrylamide gels. Its mobility on sodium dodecyl sulfate gels is consistent with a molecular weight of approximately 70 000. The amino acid composition shows that protein C-14 has an acidic:basic amino acid ratio of 1.8. Its amino terminal amino acid is lysine. Protein C-14 stimulated the incorporation of [3H]UMP into RNA by approximately 30% when added to naked DNA and homologous RNA polymerase I. A 30% stimulation of [3H]UMP incorporation into RNA was also found when protein C-14 was added to an E. coli RNA polymerase system containing either E. coli or Novikoff hepatoma DNA."}
{"id": "PMID:193561", "title": "Substrate form of D-frutose 1,6-bisphosphate utilized by fructose 1,6-bisphosphatase.", "content": "Rapid quench kinetic experiments on fructose 1,6-bisphosphatase demonstrate a stereospecificity for the alpha anomer of fructose 1,6-bisphosphate relative to the beta configuration. The beta anomer is only utilized after mutarotation to the alpha form in a process that is not enzyme catalyzed. Studies employing analogues of the acyclic keto configuration indicate that the keto form is utilized at a rate less than 5% that of the alpha anomer, a finding also confirmed by computer simulation of the rapid quench data. Chemical trapping experiments of the keto analogue, xylulose 1,5-bisphosphate, and the normal substrate suggest that interconversion of the acyclic and anomeric configurations is retarded by their binding to the enzyme. A hypothesis is advanced attributing substrate inhibition of fructose 1,6-bisphosphatase to possible binding of the keto species.", "contents": "Substrate form of D-frutose 1,6-bisphosphate utilized by fructose 1,6-bisphosphatase. Rapid quench kinetic experiments on fructose 1,6-bisphosphatase demonstrate a stereospecificity for the alpha anomer of fructose 1,6-bisphosphate relative to the beta configuration. The beta anomer is only utilized after mutarotation to the alpha form in a process that is not enzyme catalyzed. Studies employing analogues of the acyclic keto configuration indicate that the keto form is utilized at a rate less than 5% that of the alpha anomer, a finding also confirmed by computer simulation of the rapid quench data. Chemical trapping experiments of the keto analogue, xylulose 1,5-bisphosphate, and the normal substrate suggest that interconversion of the acyclic and anomeric configurations is retarded by their binding to the enzyme. A hypothesis is advanced attributing substrate inhibition of fructose 1,6-bisphosphatase to possible binding of the keto species."}
{"id": "PMID:193562", "title": "Binding of CO to mutant alpha chains of hemoglobin M Iwate; evidence for distal imidazole ligation.", "content": "The optical contribution of the beta chains to the spectrum of hemoglobin M Iwate (alpha87his leads to tyr)2beta2a was subtracted with the aid of a computer so that the spectrum of ferric alpha chains was obtained. Tyrosinate binding to the heme is suggested from spectral resemblance to ferric heme phenolate in dimethyl sulfoxide. The slow reduction of the abnormal ferric alpha chains in hemoglobin M Iwate by dithionite was studied spectrophotometrically both in the presence and absence of CO. The rate of reduction was found to be dependent on the state of ligation of the normal beta chains. The CO-ligated form of the reduced alpha chains bears strong spectral resemblance to the CO-ligated form of the reduced beta chains suggesting similar structures for the heme-ligand complex. A model compound with similar optical properties to the CO-ligated protein can be prepared in dimethyl sulfoxide from hemin chloride, imidazole, and CO using chromous acetate as the heme reductant. Substitution of phenolate for imidazole produces a spectral entity so different from that observed in the protein as to rule out tyrosinate ligation to ferrous heme of the alpha chains when CO is bound.", "contents": "Binding of CO to mutant alpha chains of hemoglobin M Iwate; evidence for distal imidazole ligation. The optical contribution of the beta chains to the spectrum of hemoglobin M Iwate (alpha87his leads to tyr)2beta2a was subtracted with the aid of a computer so that the spectrum of ferric alpha chains was obtained. Tyrosinate binding to the heme is suggested from spectral resemblance to ferric heme phenolate in dimethyl sulfoxide. The slow reduction of the abnormal ferric alpha chains in hemoglobin M Iwate by dithionite was studied spectrophotometrically both in the presence and absence of CO. The rate of reduction was found to be dependent on the state of ligation of the normal beta chains. The CO-ligated form of the reduced alpha chains bears strong spectral resemblance to the CO-ligated form of the reduced beta chains suggesting similar structures for the heme-ligand complex. A model compound with similar optical properties to the CO-ligated protein can be prepared in dimethyl sulfoxide from hemin chloride, imidazole, and CO using chromous acetate as the heme reductant. Substitution of phenolate for imidazole produces a spectral entity so different from that observed in the protein as to rule out tyrosinate ligation to ferrous heme of the alpha chains when CO is bound."}
{"id": "PMID:193565", "title": "Plasma membranes from cardiac cells in culture. Enzymatic radio-iodination, evaluation of preparation and properties of the sarcolema.", "content": "Plasma membranes from heart (sarcolemma) were prepared by the method of Kidwai, A.M. (1975) Methods in Enzymology (Fleischer, S. and Packer, L., eds.), Vol XXXIA, pp. 134--144, Academic Press, New York). On many occasions the sarcolemmal fraction identified by the enzyme markers such as (Na+ + K+)-ATPase banded at heavier densities (d greater than 1.25 g/ml) than expected for plasma membrane (d less than 1.15 g/ml). Radio-iodination of the membrane was added as an independent marker and conditions for the reproducible preparation of the sarcolemma were studied. Cultured heart cells were enzymatically iodinated under conditions which did not affect viability and labeled primarily the sarcolemma. The distribution of radioactivity in homogenates of cultured cells on the density gradient corresponded to that of the enzymes' activity. The best sarcolemma preparation was obtained with 0.3 M KCl extraction of heart homogenates in the presence of 0.05 M pyrophosphate, especially if the salt was also present during the fractionation by density gradient centrifugation. Alterations in the density were also observed with erythrocytes and cultured liver cells' plasma membrane. The data suggests a meta-stable state of the plasma membranes due to handling or storage which could cause alterations of some of their physical properties (e.g. density).", "contents": "Plasma membranes from cardiac cells in culture. Enzymatic radio-iodination, evaluation of preparation and properties of the sarcolema. Plasma membranes from heart (sarcolemma) were prepared by the method of Kidwai, A.M. (1975) Methods in Enzymology (Fleischer, S. and Packer, L., eds.), Vol XXXIA, pp. 134--144, Academic Press, New York). On many occasions the sarcolemmal fraction identified by the enzyme markers such as (Na+ + K+)-ATPase banded at heavier densities (d greater than 1.25 g/ml) than expected for plasma membrane (d less than 1.15 g/ml). Radio-iodination of the membrane was added as an independent marker and conditions for the reproducible preparation of the sarcolemma were studied. Cultured heart cells were enzymatically iodinated under conditions which did not affect viability and labeled primarily the sarcolemma. The distribution of radioactivity in homogenates of cultured cells on the density gradient corresponded to that of the enzymes' activity. The best sarcolemma preparation was obtained with 0.3 M KCl extraction of heart homogenates in the presence of 0.05 M pyrophosphate, especially if the salt was also present during the fractionation by density gradient centrifugation. Alterations in the density were also observed with erythrocytes and cultured liver cells' plasma membrane. The data suggests a meta-stable state of the plasma membranes due to handling or storage which could cause alterations of some of their physical properties (e.g. density)."}
{"id": "PMID:193566", "title": "ESR and optical absorption evidence for free radical involvement in the photosensitizing action of furocoumarin derivatives and for their singlet oxygen production.", "content": "Frozen aqueous solutions of thymine and its derivatives were irradiated with visible light (lambda greater than 320 nm) in the presence of various furocoumarins. ESR analysis revealed the induction of hydrogen adduct free radicals at C-6 position of thymine, only with those furocoumarin derivatives which show a skin-photosensitizing ability. It has been shown, moreover, that the photocycloaddition of psoralen to thymine, which is responsible for the biological effects of this dye, is inhibited when the induction of free radicals in thymine moiety has been prevented by electron scavengers. It is suggested that the free radicals observed could be involved in the biological photosensitization. The mechanism of free radical generation and singlet oxygen production by furoccoumarins were also investigated.", "contents": "ESR and optical absorption evidence for free radical involvement in the photosensitizing action of furocoumarin derivatives and for their singlet oxygen production. Frozen aqueous solutions of thymine and its derivatives were irradiated with visible light (lambda greater than 320 nm) in the presence of various furocoumarins. ESR analysis revealed the induction of hydrogen adduct free radicals at C-6 position of thymine, only with those furocoumarin derivatives which show a skin-photosensitizing ability. It has been shown, moreover, that the photocycloaddition of psoralen to thymine, which is responsible for the biological effects of this dye, is inhibited when the induction of free radicals in thymine moiety has been prevented by electron scavengers. It is suggested that the free radicals observed could be involved in the biological photosensitization. The mechanism of free radical generation and singlet oxygen production by furoccoumarins were also investigated."}
{"id": "PMID:193567", "title": "Specific effects of spermine on ouabain-sensitive and potassium-dependent phosphatase activity of kidney plasma membranes. Specificity of the potassium sites.", "content": "Specific inhibition of ouabain-sensitive and K+-dependent p-nitrophenyl-phosphatase activity of rabbit kidney plasma membranes by spermine (N,N'-bis(3-aminopropyl)-1,4-butanediamine) was characterized kinetically. 1. Inhibition by spermine was competitive with K+. The Ki for spermine was 31 micronM in the presence of 1 mM Mg2+. 2. Excess Mg2+ inhibited the ouabain-sensitive phosphatase activity in competition with K+. The Ki for Mg2+ was 2.6 mM. 3. Increasing Mg2+ concentrations reduced the spermine inhibition. This could be observed at Mg2+ concentrations higher than that of K+. 4. In the absence of inhibition by Mg2+, spermine was noncompetitive with Mg2+ which was essential for the ouabain-sensitive phosphatase activity. This could be observed at Mg2+ concentrations lower than that of K+. 5. Although Ca2+ was a strong inhibitor of the ouabain-sensitive phosphatase activity in the presence of K+, it produced a small stimulation of the activity in the absence of K+. Approximately 0.1 mM Ca2+ gave the maximum stimulation. 6. The observed Ca2+- and Mg2+-dependent phosphatase activity was inhibited strongly by ouabain and by spermine. The half-maximal inhibition concentrations of ouabain and spermine were 0.1 and 63 micronM, respectively. It is likely that Mg2+, Ca2+ and spermine bind to the same site as does K+.", "contents": "Specific effects of spermine on ouabain-sensitive and potassium-dependent phosphatase activity of kidney plasma membranes. Specificity of the potassium sites. Specific inhibition of ouabain-sensitive and K+-dependent p-nitrophenyl-phosphatase activity of rabbit kidney plasma membranes by spermine (N,N'-bis(3-aminopropyl)-1,4-butanediamine) was characterized kinetically. 1. Inhibition by spermine was competitive with K+. The Ki for spermine was 31 micronM in the presence of 1 mM Mg2+. 2. Excess Mg2+ inhibited the ouabain-sensitive phosphatase activity in competition with K+. The Ki for Mg2+ was 2.6 mM. 3. Increasing Mg2+ concentrations reduced the spermine inhibition. This could be observed at Mg2+ concentrations higher than that of K+. 4. In the absence of inhibition by Mg2+, spermine was noncompetitive with Mg2+ which was essential for the ouabain-sensitive phosphatase activity. This could be observed at Mg2+ concentrations lower than that of K+. 5. Although Ca2+ was a strong inhibitor of the ouabain-sensitive phosphatase activity in the presence of K+, it produced a small stimulation of the activity in the absence of K+. Approximately 0.1 mM Ca2+ gave the maximum stimulation. 6. The observed Ca2+- and Mg2+-dependent phosphatase activity was inhibited strongly by ouabain and by spermine. The half-maximal inhibition concentrations of ouabain and spermine were 0.1 and 63 micronM, respectively. It is likely that Mg2+, Ca2+ and spermine bind to the same site as does K+."}
{"id": "PMID:193568", "title": "Lipoamide dehyrogenase immobilized on porous glass.", "content": "Lipoamide dehydrogenase (NADH:lipoamide oxidoreductase, EC 1.6.4.3) isolate from pig heart and Escherichia coli was covalently coupled by both diazonium and amide bonds to controlled pore glass beads (96% silica). When the enzyme was immobilized in the presence of NAD+, the enzyme no longer exhibited its normal requirement for NAD+ for full activity. If the immobilized enzyme was then treated with NADase, the requirement for NAD+ was restored. Enzyme immobilized in the absence of NAD+ exhibited normal NAD+ dependence both prior to an after NADase treatment. These results are discussed in terms of co-immobilization of NAD+ at or near the allosteric site of the enzyme.", "contents": "Lipoamide dehyrogenase immobilized on porous glass. Lipoamide dehydrogenase (NADH:lipoamide oxidoreductase, EC 1.6.4.3) isolate from pig heart and Escherichia coli was covalently coupled by both diazonium and amide bonds to controlled pore glass beads (96% silica). When the enzyme was immobilized in the presence of NAD+, the enzyme no longer exhibited its normal requirement for NAD+ for full activity. If the immobilized enzyme was then treated with NADase, the requirement for NAD+ was restored. Enzyme immobilized in the absence of NAD+ exhibited normal NAD+ dependence both prior to an after NADase treatment. These results are discussed in terms of co-immobilization of NAD+ at or near the allosteric site of the enzyme."}
{"id": "PMID:193569", "title": "Radial diffusion assay of tissue collagenase and its application in evaluation of collagenase inhibitors.", "content": "A radial diffusion assay for tissue collagenase (EC 3.4.24.3) has been devised which is simple, sensitive and capable of application to large numbers of samples. The assay employs an agarose matrix containing solubilized lathyritic rat skin collagen as substrate. Fibril formation is induced for 2 h at 37 degrees C subsequent to 41 h digestion at 28 degrees C. The procedure results in sharply defined zones of lysis which may be measured directly or after photography. The characteristics of the procedure are otherwise similar to those reported for other radial diffusion assays. The new method was used to examine the action of 10 compounds which were known or potential inhibitors of tadpole collagenase. The concentration of inhibitor required to produce 50% inhibition is reported for the following compounds: alpha2-macroglobulin, 142 microng/ml; N-acetylcysteine, greater than or equal to 100 mM; cysteine, 8.7 mM; EDTA, 0.46 mM; histidine, greater than or equal to 100 mM; 2,3-dimercaptopropanol, 0.5 mM and mercaptoacetic acid, 70 mM. The procedure also has potential for clinical determinations (e.g. tears, synovial fluid) since assay dishes may be prepared in advance and only 15 micronl of sample is required.", "contents": "Radial diffusion assay of tissue collagenase and its application in evaluation of collagenase inhibitors. A radial diffusion assay for tissue collagenase (EC 3.4.24.3) has been devised which is simple, sensitive and capable of application to large numbers of samples. The assay employs an agarose matrix containing solubilized lathyritic rat skin collagen as substrate. Fibril formation is induced for 2 h at 37 degrees C subsequent to 41 h digestion at 28 degrees C. The procedure results in sharply defined zones of lysis which may be measured directly or after photography. The characteristics of the procedure are otherwise similar to those reported for other radial diffusion assays. The new method was used to examine the action of 10 compounds which were known or potential inhibitors of tadpole collagenase. The concentration of inhibitor required to produce 50% inhibition is reported for the following compounds: alpha2-macroglobulin, 142 microng/ml; N-acetylcysteine, greater than or equal to 100 mM; cysteine, 8.7 mM; EDTA, 0.46 mM; histidine, greater than or equal to 100 mM; 2,3-dimercaptopropanol, 0.5 mM and mercaptoacetic acid, 70 mM. The procedure also has potential for clinical determinations (e.g. tears, synovial fluid) since assay dishes may be prepared in advance and only 15 micronl of sample is required."}
{"id": "PMID:193570", "title": "An essential arginine residue in the ATP-binding centre of (Na+ + K+)-ATPase.", "content": "1. Incubation of purified (Na+ + K+)-ATPase (ATP phosphohydrolase EC 3.6.1.3) from rabbit kidney outer medulla with butanedione in borate buffer leads to reversible inactivation of the (Na+ + K+)-ATPase activity. 2. The reaction shows second-outer kinetics, suggesting that modification of a single amino acid residue is involved in the inactivation of the enzyme. 3. The pH dependence of the reaction and the effect of borate ions strongly suggest that modification of an arginine residue is involved. 4. Replacement of Na+ by K+ in the butanedione medium decreases inactivation. 5. ATP, ADP and adenylyl imido diphosphate, particularly in the presence of trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid to complex Mg2+, protect the enzyme very efficiently against inactivation by butanedione. 6. The (Na+ + Mg2+)-dependent phosphorylation capacity of the enzyme is inhibited in the same degree as the (Na+ + K+)-ATPase activity by butanedione. 7. The K+-stimulated p-nitrophenylphosphatase activity is much less inhibited than the (Na+ + K+)ATPase activity. 8. The ATP stimulation of the K+-stimulated p-nitrophenylphosphatase activity is inhibited by butanedione to the same extent as the (Na+ + K+)-ATPase activity. 9. Modification of sulfhydryl groups with 5,5'-dithiobis(2-nitrobenzoic acid) protects partially against the inactivating effect of butanedione. 10. The results suggest that an arginine residue is present in the nucleotide binding centre of the enzyme.", "contents": "An essential arginine residue in the ATP-binding centre of (Na+ + K+)-ATPase. 1. Incubation of purified (Na+ + K+)-ATPase (ATP phosphohydrolase EC 3.6.1.3) from rabbit kidney outer medulla with butanedione in borate buffer leads to reversible inactivation of the (Na+ + K+)-ATPase activity. 2. The reaction shows second-outer kinetics, suggesting that modification of a single amino acid residue is involved in the inactivation of the enzyme. 3. The pH dependence of the reaction and the effect of borate ions strongly suggest that modification of an arginine residue is involved. 4. Replacement of Na+ by K+ in the butanedione medium decreases inactivation. 5. ATP, ADP and adenylyl imido diphosphate, particularly in the presence of trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid to complex Mg2+, protect the enzyme very efficiently against inactivation by butanedione. 6. The (Na+ + Mg2+)-dependent phosphorylation capacity of the enzyme is inhibited in the same degree as the (Na+ + K+)-ATPase activity by butanedione. 7. The K+-stimulated p-nitrophenylphosphatase activity is much less inhibited than the (Na+ + K+)ATPase activity. 8. The ATP stimulation of the K+-stimulated p-nitrophenylphosphatase activity is inhibited by butanedione to the same extent as the (Na+ + K+)-ATPase activity. 9. Modification of sulfhydryl groups with 5,5'-dithiobis(2-nitrobenzoic acid) protects partially against the inactivating effect of butanedione. 10. The results suggest that an arginine residue is present in the nucleotide binding centre of the enzyme."}
{"id": "PMID:193571", "title": "Altered regulation of cyclic AMP-dependent protein kinase in a mouse lymphoma cell line.", "content": "The ability of cyclic AMP to inhibit growth, cause cytolysis and induce synthesis of cyclic AMP-phosphodiesterase in S49.1 mouse lymphoma cells is deficient in cells selected on the basis of their resistance to killing by 2 mM dibutyryl cyclic AMP. The properties of the cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) in the cyclic AMP-sensitive (S) and cyclic AMP-resistant (R) lymphoma cells were comparatively studied. The cyclic AMP-dependent protein kinase activity or R cells cytosol exhibits an apparent Ka for activation by cyclic AMP 100-fold greater than that of the enzyme from the parental S cells. The free regulatory and catalytic subunits from both S and R kinase are thermolabile, when associated in the holoenzyme the two subunits are more stable to heat inactivation in R kinase than in S kinase. The increased heat stability of R kinase is observed however only for the enzyme in which the catalytic and cyclic AMP-binding activities are expressed at high cyclic AMP concentrations (10(-5)--10(-4) M), the activities expressed at low cyclic AMP concentrations (10(-9)--10(-6) M) being thermolabile. The regulatory subunit of S kinase can be stabilized against heat inactivation by cyclic AMP binding both at 2-10(-7) and 10(-5) M cyclic AMP concentrations. In contrast, the regulatory subunit-cyclic AMP complex from R kinase is stable to heat inactivation only when formed in the presence of high cyclic AMP concentrations (10(-5)M). The findings indicate that the transition from a cyclic AMP-sensitive to a cyclic AMP-resistant lymphoma cell phenotype is related to a structural alteration in the regulatory subunit of the cyclic AMP-dependent protein kinase which has affected the protein's affinity for cyclic AMP and its interaction with the catalytic subunit.", "contents": "Altered regulation of cyclic AMP-dependent protein kinase in a mouse lymphoma cell line. The ability of cyclic AMP to inhibit growth, cause cytolysis and induce synthesis of cyclic AMP-phosphodiesterase in S49.1 mouse lymphoma cells is deficient in cells selected on the basis of their resistance to killing by 2 mM dibutyryl cyclic AMP. The properties of the cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) in the cyclic AMP-sensitive (S) and cyclic AMP-resistant (R) lymphoma cells were comparatively studied. The cyclic AMP-dependent protein kinase activity or R cells cytosol exhibits an apparent Ka for activation by cyclic AMP 100-fold greater than that of the enzyme from the parental S cells. The free regulatory and catalytic subunits from both S and R kinase are thermolabile, when associated in the holoenzyme the two subunits are more stable to heat inactivation in R kinase than in S kinase. The increased heat stability of R kinase is observed however only for the enzyme in which the catalytic and cyclic AMP-binding activities are expressed at high cyclic AMP concentrations (10(-5)--10(-4) M), the activities expressed at low cyclic AMP concentrations (10(-9)--10(-6) M) being thermolabile. The regulatory subunit of S kinase can be stabilized against heat inactivation by cyclic AMP binding both at 2-10(-7) and 10(-5) M cyclic AMP concentrations. In contrast, the regulatory subunit-cyclic AMP complex from R kinase is stable to heat inactivation only when formed in the presence of high cyclic AMP concentrations (10(-5)M). The findings indicate that the transition from a cyclic AMP-sensitive to a cyclic AMP-resistant lymphoma cell phenotype is related to a structural alteration in the regulatory subunit of the cyclic AMP-dependent protein kinase which has affected the protein's affinity for cyclic AMP and its interaction with the catalytic subunit."}
{"id": "PMID:193572", "title": "Purification and molecular properties of the AMP-activated pyruvate kinase from Escherichia coli.", "content": "The AMP-activated pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) from Escherichia coli has been purified 200 times through a three-step procedure which gives a homogeneous preparation with a specific activity of 110. The enzyme appears to be a tetramer of molecular weight 190 000. Subunits (molecular weight 51 000) show a single amino-terminal amino acid (serine) and appear as a single band in polyacrylamide gel electrophoresis in sodium dodecyl sulphate. The enzyme crystallizes in conditions of reduced dielectric constant of the solvent in the pH range 6.5-7.5. Kinetic and regulatory properties of the purified enzyme are similar to those described for crude preparations of the enzyme.", "contents": "Purification and molecular properties of the AMP-activated pyruvate kinase from Escherichia coli. The AMP-activated pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) from Escherichia coli has been purified 200 times through a three-step procedure which gives a homogeneous preparation with a specific activity of 110. The enzyme appears to be a tetramer of molecular weight 190 000. Subunits (molecular weight 51 000) show a single amino-terminal amino acid (serine) and appear as a single band in polyacrylamide gel electrophoresis in sodium dodecyl sulphate. The enzyme crystallizes in conditions of reduced dielectric constant of the solvent in the pH range 6.5-7.5. Kinetic and regulatory properties of the purified enzyme are similar to those described for crude preparations of the enzyme."}
{"id": "PMID:193573", "title": "The role of bound thiamine pyrophosphate in the synthesis of thiamine triphosphate in rat liver.", "content": "Thiamine pyrophosphate-ATP phosphoryltransferase, the enzyme that catalyzes the synthesis of thiamine triphosphate, has been found in the supernatant fraction of rat liver. The substrate for the enzyme is endogenous, bound thiamine pyrophosphate, since the addition of exogenous thiamine pyrophosphate had no effect. Thus, when a rat liver supernatant was incubated with gamma-labelled [32P]ATP, thiamine [32P]triphosphate was formed whereas the incubation of thiamine [32P]pyrophosphate with ATP did not produce thiamine [32P]triphosphate. The endogenous thiamine pyrophosphate was found to be bound to a high molecular weight protein which comes out in the void volume of Sephadex G-75, and is not dialyzable. The activity that catalyzes the formation of thiamine triphosphate has an optimum pH between 6 and 6.5, a linear time course of thiamine triphosphate synthesis up to 30 min, and is not affected by Ca2+, cyclic GMP and sulfhydryl reagents.", "contents": "The role of bound thiamine pyrophosphate in the synthesis of thiamine triphosphate in rat liver. Thiamine pyrophosphate-ATP phosphoryltransferase, the enzyme that catalyzes the synthesis of thiamine triphosphate, has been found in the supernatant fraction of rat liver. The substrate for the enzyme is endogenous, bound thiamine pyrophosphate, since the addition of exogenous thiamine pyrophosphate had no effect. Thus, when a rat liver supernatant was incubated with gamma-labelled [32P]ATP, thiamine [32P]triphosphate was formed whereas the incubation of thiamine [32P]pyrophosphate with ATP did not produce thiamine [32P]triphosphate. The endogenous thiamine pyrophosphate was found to be bound to a high molecular weight protein which comes out in the void volume of Sephadex G-75, and is not dialyzable. The activity that catalyzes the formation of thiamine triphosphate has an optimum pH between 6 and 6.5, a linear time course of thiamine triphosphate synthesis up to 30 min, and is not affected by Ca2+, cyclic GMP and sulfhydryl reagents."}
{"id": "PMID:193574", "title": "The proteolytic action of bacterial proteases from Clostridium histolyticum on bovine fibrinogen.", "content": "Bacterial proteases from Clostridium histolyticum bring about the polymerization of fibrinogen into structured fibres, the period being 9 nm when the ionic strength (I)  of the solution is between 0.1 and 0.2. At I=0.3 no polymerization occurs, but the successive actions of bacterial proteases and thrombin induce polymerization, the fibres obtained showing a periodic structure: the major period is 23 nm with two minor striations. The striation pattern is different from that obtained with fibrin which shows a major period of 23 nm with three minor striations. The degree of degradation of fibrinogen monitored by disc gel electrophoresis shows that the Aalpha polypeptide chain (mol. wt.=68 000) is degraded into Aalpha1 (mol. wt.=32 000) and Aalpha2 (mol. wt.=29 000), whilst the mobility of Bbeta increases and gamma remains unchanged; the molecular weight is estimated between 272 000 and 269 000. These results emphasize that the charge distribution differences which are compatible with the loss of different portions of the molecule, lead to variations in fibre structures.", "contents": "The proteolytic action of bacterial proteases from Clostridium histolyticum on bovine fibrinogen. Bacterial proteases from Clostridium histolyticum bring about the polymerization of fibrinogen into structured fibres, the period being 9 nm when the ionic strength (I)  of the solution is between 0.1 and 0.2. At I=0.3 no polymerization occurs, but the successive actions of bacterial proteases and thrombin induce polymerization, the fibres obtained showing a periodic structure: the major period is 23 nm with two minor striations. The striation pattern is different from that obtained with fibrin which shows a major period of 23 nm with three minor striations. The degree of degradation of fibrinogen monitored by disc gel electrophoresis shows that the Aalpha polypeptide chain (mol. wt.=68 000) is degraded into Aalpha1 (mol. wt.=32 000) and Aalpha2 (mol. wt.=29 000), whilst the mobility of Bbeta increases and gamma remains unchanged; the molecular weight is estimated between 272 000 and 269 000. These results emphasize that the charge distribution differences which are compatible with the loss of different portions of the molecule, lead to variations in fibre structures."}
{"id": "PMID:193575", "title": "[Extraction of deuterated compounds from Chlorella sp. K. grown in D20].", "content": "A comparison of the three known methods made it possible to work out methods of complex extraction of deutero amino acids, deutero sugars and deutero vitamins from algae Chlorella sp. K., grown autotrophically in heavy water. An analysis of the isotopic composition of deutero amino acids by PMR indicates that treatment with HCl introduces 1H into side chains of some amino acids by chemical exchange (C2, 6H of tyrosine, C2H of histidine, rho-H of phenylalanin, beta-CH2-aspartate and gamma-CH2-glutamate. These exchanges made the amino acids convenient to be used as the substrates for the growth of heterotrophic selective deuterated organisms as a source of selective deuterated proteins.", "contents": "[Extraction of deuterated compounds from Chlorella sp. K. grown in D20]. A comparison of the three known methods made it possible to work out methods of complex extraction of deutero amino acids, deutero sugars and deutero vitamins from algae Chlorella sp. K., grown autotrophically in heavy water. An analysis of the isotopic composition of deutero amino acids by PMR indicates that treatment with HCl introduces 1H into side chains of some amino acids by chemical exchange (C2, 6H of tyrosine, C2H of histidine, rho-H of phenylalanin, beta-CH2-aspartate and gamma-CH2-glutamate. These exchanges made the amino acids convenient to be used as the substrates for the growth of heterotrophic selective deuterated organisms as a source of selective deuterated proteins."}
{"id": "PMID:193581", "title": "[Cooperative properties of D-glyceraldehyde-3-phosphate dehydrogenase].", "content": "The structure of the active center of glyceraldehyde-3-phosphate dehydrogenase and the arrangement of subunits in the tetrameric molecule is delineated. The mechanism of cooperative effects in the oligomer is considered, and the involvement of various regions of the active center and of different-subunit contact area in the realization of the cooperative phenomena is discussed. A special attention is paid to the effect of NAD+ bound to one of the subunits of the tetramer on the structure of an adjacent subunit and to the problem of the participation of the coenzyme in the creation of anion-binding sites of the enzyme. The conditions of reversible dissociation of the tetrameric apoenzyme molecule into dimers are depicted, and the role of NAD+ in the organization of the quaternary structure of the dehydrogenase is discussed. The problem of catalytic activity of the dimeric form of the enzyme is argued.", "contents": "[Cooperative properties of D-glyceraldehyde-3-phosphate dehydrogenase]. The structure of the active center of glyceraldehyde-3-phosphate dehydrogenase and the arrangement of subunits in the tetrameric molecule is delineated. The mechanism of cooperative effects in the oligomer is considered, and the involvement of various regions of the active center and of different-subunit contact area in the realization of the cooperative phenomena is discussed. A special attention is paid to the effect of NAD+ bound to one of the subunits of the tetramer on the structure of an adjacent subunit and to the problem of the participation of the coenzyme in the creation of anion-binding sites of the enzyme. The conditions of reversible dissociation of the tetrameric apoenzyme molecule into dimers are depicted, and the role of NAD+ in the organization of the quaternary structure of the dehydrogenase is discussed. The problem of catalytic activity of the dimeric form of the enzyme is argued."}
{"id": "PMID:193580", "title": "[2 types of reduction of P700+ reaction centers in the leaves of green plants].", "content": "It is shown that in the leaves of Hibiscous sp. the ESR signal I rises under weak far red light after its partial inhibition with a short white flash is slower than after adaptation to 710 nm light and short dark exposition. It is suggested that this divergence in the ESR kinetics is due to the fact that only part of reduced intermediates generated by the photosystem 2 under flash is readily available to P700+, whereas other reducing reagents slowly react with the photosystem 1 reaction centres.", "contents": "[2 types of reduction of P700+ reaction centers in the leaves of green plants]. It is shown that in the leaves of Hibiscous sp. the ESR signal I rises under weak far red light after its partial inhibition with a short white flash is slower than after adaptation to 710 nm light and short dark exposition. It is suggested that this divergence in the ESR kinetics is due to the fact that only part of reduced intermediates generated by the photosystem 2 under flash is readily available to P700+, whereas other reducing reagents slowly react with the photosystem 1 reaction centres."}
{"id": "PMID:193585", "title": "Thyroxine effect upon activity of uridine kinase in developing rat cerebellum.", "content": "Experimental hyperthyroidism in the neonatal rat is known to accelerate cerebellar DNA biosynthesis resulting ultimately in a deficit in cell number at maturity. Because of the know shift to an earlier age in the developmental curve for cerebellar thymidine kinase activity in rats treated with thyroxine, we studied the activity of uridine kinase and DNA biosynthesis during rat cerebellar development under hyperthyroid conditions. Body weight and cerebellar wet weight in treated animals were noted to be significantly decreased below control values on days 4 and 12, respectively. Cerebellar DNA was significantly elevated above control values on days 4 and 6 (132 and 129% of control, respectively). Subsequently, DNA content fell significantly below control values through day 18. Uridine kinase activity was found to be increased significantly above control values at ages 2, 4, and 6 days (maximum 119% of control at age 4 days) following which activity fell significantly below control values by 15 days of age. Uridine kinase activity from both treated and control animals fell only moderately after the time of peak activity between 9 and 15 days of age, although the peak of the developmental curve for the enzyme appeared earlier in the treated animals. The data show a less pronounced early stimulation of cerebellar uridine kinase by thyroxine compared with previously reported thyroxine enhancement of thymidine kinase activity, although both enzymes are affected by thyroxine throughout cerebellar ontogenesis. The study thus provides evidence that uridine kinase is sensitive to hormonal stimulation during early stages of active cerebellar cell division, and that the enzyme may relate most closely in brain to the synthesis of RNA as well as the sustaining of cell function after the most active phase of cellular proliferation. In addition, the study emphasizes the use of enzyme-hormone relationships during development to provide information concerning critical interrelationships between metabolic pathways contributing to nucleic acid biosynthesis.", "contents": "Thyroxine effect upon activity of uridine kinase in developing rat cerebellum. Experimental hyperthyroidism in the neonatal rat is known to accelerate cerebellar DNA biosynthesis resulting ultimately in a deficit in cell number at maturity. Because of the know shift to an earlier age in the developmental curve for cerebellar thymidine kinase activity in rats treated with thyroxine, we studied the activity of uridine kinase and DNA biosynthesis during rat cerebellar development under hyperthyroid conditions. Body weight and cerebellar wet weight in treated animals were noted to be significantly decreased below control values on days 4 and 12, respectively. Cerebellar DNA was significantly elevated above control values on days 4 and 6 (132 and 129% of control, respectively). Subsequently, DNA content fell significantly below control values through day 18. Uridine kinase activity was found to be increased significantly above control values at ages 2, 4, and 6 days (maximum 119% of control at age 4 days) following which activity fell significantly below control values by 15 days of age. Uridine kinase activity from both treated and control animals fell only moderately after the time of peak activity between 9 and 15 days of age, although the peak of the developmental curve for the enzyme appeared earlier in the treated animals. The data show a less pronounced early stimulation of cerebellar uridine kinase by thyroxine compared with previously reported thyroxine enhancement of thymidine kinase activity, although both enzymes are affected by thyroxine throughout cerebellar ontogenesis. The study thus provides evidence that uridine kinase is sensitive to hormonal stimulation during early stages of active cerebellar cell division, and that the enzyme may relate most closely in brain to the synthesis of RNA as well as the sustaining of cell function after the most active phase of cellular proliferation. In addition, the study emphasizes the use of enzyme-hormone relationships during development to provide information concerning critical interrelationships between metabolic pathways contributing to nucleic acid biosynthesis."}
{"id": "PMID:193586", "title": "Behavioral and psychological correlates of a difference in chronic sleep duration.", "content": "The relationship between chronic differences in sleep duration and waking behaviors was explored by comparing two groups of 10 healthy male university students who regularly slept nocturnally for 7-8 h or for 9.5-10.5 h. Measurements were obtained of sublingual temperature, from a 45 min Wilkinson auditory vigilance task and a mood adjective check list 30 min after awakening in the morning, at midday ind in the early evening following an electroencephalographically recorded night of sleep. In both subject groups body temperature increased from morning to early evening, while misses on the vigilance task correspondingly declined during the day. The average daily level of oral temperature and performance were significantly lower in the 7-8 h (control) group than in the long sleepers. Positive mood states (Cheerful, Energetic, General Activation, High Activation) were significantly  greater and negative affects (Anger-Hostility, Depression) significantly less in the long sleepers. As a result of the mean difference in total sleep time existing between groups control subjects averaged significantly less stage 2, and stage REM sleep. It was postulated that there were behavioral deficits in the control group attirbutable either to selective sleep stage deprivation or to the general consequence of reduced sleep per se or to both of these factors.", "contents": "Behavioral and psychological correlates of a difference in chronic sleep duration. The relationship between chronic differences in sleep duration and waking behaviors was explored by comparing two groups of 10 healthy male university students who regularly slept nocturnally for 7-8 h or for 9.5-10.5 h. Measurements were obtained of sublingual temperature, from a 45 min Wilkinson auditory vigilance task and a mood adjective check list 30 min after awakening in the morning, at midday ind in the early evening following an electroencephalographically recorded night of sleep. In both subject groups body temperature increased from morning to early evening, while misses on the vigilance task correspondingly declined during the day. The average daily level of oral temperature and performance were significantly lower in the 7-8 h (control) group than in the long sleepers. Positive mood states (Cheerful, Energetic, General Activation, High Activation) were significantly  greater and negative affects (Anger-Hostility, Depression) significantly less in the long sleepers. As a result of the mean difference in total sleep time existing between groups control subjects averaged significantly less stage 2, and stage REM sleep. It was postulated that there were behavioral deficits in the control group attirbutable either to selective sleep stage deprivation or to the general consequence of reduced sleep per se or to both of these factors."}
{"id": "PMID:193587", "title": "EEG theta waves and psychological phenomena: a review and analysis.", "content": "In this paper, studies which have explored the relation between EEG theta waves and psychological phenomena in normal human subjects are reviewed. It is noted that increases in theta activity occur in conjunction with several kinds of psychological processes. The importance of ocnsidering properties of theta activity, such as amplitude, rhythmicity and scalp topography when analyzing the relation between theta and psychological processes is emphasized. Although there is some evidence for a relationship between theta and psychological processes, it is concluded that the degree to which properties of theta activity are systematically related to specific psychological processes is not yet known.", "contents": "EEG theta waves and psychological phenomena: a review and analysis. In this paper, studies which have explored the relation between EEG theta waves and psychological phenomena in normal human subjects are reviewed. It is noted that increases in theta activity occur in conjunction with several kinds of psychological processes. The importance of ocnsidering properties of theta activity, such as amplitude, rhythmicity and scalp topography when analyzing the relation between theta and psychological processes is emphasized. Although there is some evidence for a relationship between theta and psychological processes, it is concluded that the degree to which properties of theta activity are systematically related to specific psychological processes is not yet known."}
{"id": "PMID:193589", "title": "Children sea-blue histiocytosis (2 cases) compared with phospholipidosis induced by 4-4' DET (4-4' p (diethylamino-2-ethoxy phenyl) 3-4 hexane) in rat.", "content": "Two cases of children with liver and spleen enlargement are reported. Sea-blue histiocytes and Pick cells were found in both cases in liver, spleen, bone marrow and blood. Further more, lysobisphodphatidic acids were identified in phospholipid analysis of liver  biopsies and cultived liver cells. Absence of neurologic involvement at 14 and 18 years fo age suggest a Crocker type C of Niemann-Pick disease, i.e. a not yet well defined entity. Resemblance of these morphological and biochemical abnormalities with certain cases of drug poisoning (especially the well-known intoxication by 4-4' DET)  is discussed on the basis of results from experimental studies with this drug in the rat.", "contents": "Children sea-blue histiocytosis (2 cases) compared with phospholipidosis induced by 4-4' DET (4-4' p (diethylamino-2-ethoxy phenyl) 3-4 hexane) in rat. Two cases of children with liver and spleen enlargement are reported. Sea-blue histiocytes and Pick cells were found in both cases in liver, spleen, bone marrow and blood. Further more, lysobisphodphatidic acids were identified in phospholipid analysis of liver  biopsies and cultived liver cells. Absence of neurologic involvement at 14 and 18 years fo age suggest a Crocker type C of Niemann-Pick disease, i.e. a not yet well defined entity. Resemblance of these morphological and biochemical abnormalities with certain cases of drug poisoning (especially the well-known intoxication by 4-4' DET)  is discussed on the basis of results from experimental studies with this drug in the rat."}
{"id": "PMID:193590", "title": "Early syncytium formation induced by bovine leukemia virus in mixed cultures.", "content": "Early syncytium formation was obtained in mixed cultures in the presence of BLV (Bovine Leukemia Virus). The phenomenon is specifically dependent upon the presence of BLV.", "contents": "Early syncytium formation induced by bovine leukemia virus in mixed cultures. Early syncytium formation was obtained in mixed cultures in the presence of BLV (Bovine Leukemia Virus). The phenomenon is specifically dependent upon the presence of BLV."}
{"id": "PMID:193591", "title": "[Quantitative analysis of the process of stimulation frequency transformation in the neuromuscular apparatus].", "content": "Dependence of parameters of the neuromuscular transmission on the stimulation frequency was determined. This dependence was analyzed as applied to the processes of synapsis \"fatigue\" occurring in prolonged rhythmic muscle stimulation. The suggested mathematical model and the method of statistical analysis of the EMG of the sum total muscle responses following from it offered a possibility of determination by the experimental data of the approximate parameters giving a quanititative expression of the frequency properties of the neuromuscular transmission.", "contents": "[Quantitative analysis of the process of stimulation frequency transformation in the neuromuscular apparatus]. Dependence of parameters of the neuromuscular transmission on the stimulation frequency was determined. This dependence was analyzed as applied to the processes of synapsis \"fatigue\" occurring in prolonged rhythmic muscle stimulation. The suggested mathematical model and the method of statistical analysis of the EMG of the sum total muscle responses following from it offered a possibility of determination by the experimental data of the approximate parameters giving a quanititative expression of the frequency properties of the neuromuscular transmission."}
{"id": "PMID:193592", "title": "[Formation of cyclic adenosine-3',5'-monophosphate in phagocytosis].", "content": "The content of cAMP in the phagocytizing macrophages increased, especially in the phagocytosis of live microbes. cAMP formed in phagocytosis was determined in the incubation medium, whereas in the cells its content remained practically unchanged. In the administration of E. coli 055 to the germ-free guinea pigs the concentration of cAMP was found to be increased in the mucosa cells of the small intestine and in the blood serum; this fact indicated that adenylcyclase system participated in the reactions of the interrelations of the microorganisms with the epithelial cells of the smal intestiine.", "contents": "[Formation of cyclic adenosine-3',5'-monophosphate in phagocytosis]. The content of cAMP in the phagocytizing macrophages increased, especially in the phagocytosis of live microbes. cAMP formed in phagocytosis was determined in the incubation medium, whereas in the cells its content remained practically unchanged. In the administration of E. coli 055 to the germ-free guinea pigs the concentration of cAMP was found to be increased in the mucosa cells of the small intestine and in the blood serum; this fact indicated that adenylcyclase system participated in the reactions of the interrelations of the microorganisms with the epithelial cells of the smal intestiine."}
{"id": "PMID:193593", "title": "[Spontaneous fluctuations in the activity of rabbit skeletal muscle NAD-kinase].", "content": "Spontaneous fluctuations in the time of the activity of the 280-300-fold purified NAD-kinase preparation from rabbit skeletal muscle following its dilution are described. Defrosted but undiluted enzyme preparation failed to exhibit any fluctuations in its activity.", "contents": "[Spontaneous fluctuations in the activity of rabbit skeletal muscle NAD-kinase]. Spontaneous fluctuations in the time of the activity of the 280-300-fold purified NAD-kinase preparation from rabbit skeletal muscle following its dilution are described. Defrosted but undiluted enzyme preparation failed to exhibit any fluctuations in its activity."}
{"id": "PMID:193594", "title": "[Changes in the kinin system components and structure of the myocardium under the influence of antikinin preparations in allergic myocarditis in rabbits].", "content": "Experimental allergic myocarditis was induced in rabbits; a study was made of the effect on the kininogen content and on the activity of kininase in the myocardium, and on its morphological structure produced by anginine, contrical, aspirin, indometacine and epsilon-aminocapronic acid. The former two preparations were much more potent (in comparison with the others) in inhibiting the activation of the myocardial kinin system and promoted restoration of the morphological structure of the myocardium. Development of an allergic inflammation in the myocardium could be arrested or decreased by inhibition of the kinin system of the plasma and myocardium by specific agents.", "contents": "[Changes in the kinin system components and structure of the myocardium under the influence of antikinin preparations in allergic myocarditis in rabbits]. Experimental allergic myocarditis was induced in rabbits; a study was made of the effect on the kininogen content and on the activity of kininase in the myocardium, and on its morphological structure produced by anginine, contrical, aspirin, indometacine and epsilon-aminocapronic acid. The former two preparations were much more potent (in comparison with the others) in inhibiting the activation of the myocardial kinin system and promoted restoration of the morphological structure of the myocardium. Development of an allergic inflammation in the myocardium could be arrested or decreased by inhibition of the kinin system of the plasma and myocardium by specific agents."}
{"id": "PMID:193595", "title": "Antagonism by PGF2alpha of the vasodilation induced by PGE1, PGE2 and PGA1 in the canine uterus.", "content": "Prostaglandins appear to play an important role in a number of reproductive processes. The present study was designed to determine if the vasodilator action of prostaglandins of the A and E series on uterine vascular smooth muscle was mediated via a receptor and if PGF2alpha could compete for this same receptor. The data demonstrate that PGF2alpha, which by itself has no uterine vascular effect, can produce a parallel shift in the dose-response curves for certain vasodilator prostaglandins. This action, which suggests competitive antagonism, may well play a role in regulating blood flow in the nonpregnant uterus.", "contents": "Antagonism by PGF2alpha of the vasodilation induced by PGE1, PGE2 and PGA1 in the canine uterus. Prostaglandins appear to play an important role in a number of reproductive processes. The present study was designed to determine if the vasodilator action of prostaglandins of the A and E series on uterine vascular smooth muscle was mediated via a receptor and if PGF2alpha could compete for this same receptor. The data demonstrate that PGF2alpha, which by itself has no uterine vascular effect, can produce a parallel shift in the dose-response curves for certain vasodilator prostaglandins. This action, which suggests competitive antagonism, may well play a role in regulating blood flow in the nonpregnant uterus."}
{"id": "PMID:193596", "title": "Current status of population kinetics in gliomas.", "content": "One must know tumor cell kinetics in order to devise a rational drug regimen for gliomas. With tritiated thymidine, the Labelling Index of astrocytomas is less than 1 per 100; of glioblastomas from 5-10 per 100. The duration of S phase is fairly constant, ranging from 7 to 10 hours. Double radioautography reveals a cell cycle time of 2 to 3 days and a Growth Fraction of 10 to 30 per 100 in glioblastomas. Calculations based on volume of tumor at recurrence after a gross total resection, analysis of primer dependent D.N.A. polymerase (P.D.P.), and analysis of cells by Flow Microfluorometer, all confirm these approximate figures. Thus most of the cells of a glioma are not sensitive to a cell-cycle phase specific drug. Such an agent, if given, should be administered over a 2 to 3 day period, in order to affect as many cells as possible. The most important part of a drug regimen should be an agent which attacks non-proliferating as well as proliferating cells, such as an alkylating agent. The effects of various drugs and schedules can be examined by animal models with the technqiue of colony forming efficiency.", "contents": "Current status of population kinetics in gliomas. One must know tumor cell kinetics in order to devise a rational drug regimen for gliomas. With tritiated thymidine, the Labelling Index of astrocytomas is less than 1 per 100; of glioblastomas from 5-10 per 100. The duration of S phase is fairly constant, ranging from 7 to 10 hours. Double radioautography reveals a cell cycle time of 2 to 3 days and a Growth Fraction of 10 to 30 per 100 in glioblastomas. Calculations based on volume of tumor at recurrence after a gross total resection, analysis of primer dependent D.N.A. polymerase (P.D.P.), and analysis of cells by Flow Microfluorometer, all confirm these approximate figures. Thus most of the cells of a glioma are not sensitive to a cell-cycle phase specific drug. Such an agent, if given, should be administered over a 2 to 3 day period, in order to affect as many cells as possible. The most important part of a drug regimen should be an agent which attacks non-proliferating as well as proliferating cells, such as an alkylating agent. The effects of various drugs and schedules can be examined by animal models with the technqiue of colony forming efficiency."}
{"id": "PMID:193597", "title": "[Treatment of inoperable glioblastomas using a combination of adriamycin, VM 26 and CCNU].", "content": "46 non resectable malignant gliomas adult patients were treated with a combination protocol of chemotherapy with administration of adriamycin, VM 26 and CCNU. The tolerance to this treatment was good except for the delayed hematological toxicity related to cumulative doses of CCNU, which limited after 5 courses of chemotherapy the possibility of further treatment with the same combination. As far as the neurological responses are concerned, 66 per 100 patients were good responders, but we found a poor relation (50%) between the degree of clinical response and regression of tumour volume in brain scan. The median survival of this group of patients was 9 months and 11 patients/46 are still alive in good state 14 months after they entered into this trial. According to these data we discuss the introduction of chemotherapy at the early stage of the disease.", "contents": "[Treatment of inoperable glioblastomas using a combination of adriamycin, VM 26 and CCNU]. 46 non resectable malignant gliomas adult patients were treated with a combination protocol of chemotherapy with administration of adriamycin, VM 26 and CCNU. The tolerance to this treatment was good except for the delayed hematological toxicity related to cumulative doses of CCNU, which limited after 5 courses of chemotherapy the possibility of further treatment with the same combination. As far as the neurological responses are concerned, 66 per 100 patients were good responders, but we found a poor relation (50%) between the degree of clinical response and regression of tumour volume in brain scan. The median survival of this group of patients was 9 months and 11 patients/46 are still alive in good state 14 months after they entered into this trial. According to these data we discuss the introduction of chemotherapy at the early stage of the disease."}
{"id": "PMID:193598", "title": "[Concentrated irradiation of malignant astrocytoma and glioblastoma].", "content": "Since 1965, 118 glioblastoma and 18 malignant astrocytomas of the adult have been treated by concentrated irradiation after a more or less complete surgical excision of the tumor. Three types of irradiation have been used; at present 3 600 rads whole brain irradiation are delivered in 2 series of 1 800 rads over 3 days 20 to 30 spaced a part. All patients receive ACTH and the tolerance has been excellent. The results of this rapid palliative therapy are quite comparable to those of more classical irradiation. Because of the very short survival of these patients, it would appear advantageous to treat them in as short a time interval as possible.", "contents": "[Concentrated irradiation of malignant astrocytoma and glioblastoma]. Since 1965, 118 glioblastoma and 18 malignant astrocytomas of the adult have been treated by concentrated irradiation after a more or less complete surgical excision of the tumor. Three types of irradiation have been used; at present 3 600 rads whole brain irradiation are delivered in 2 series of 1 800 rads over 3 days 20 to 30 spaced a part. All patients receive ACTH and the tolerance has been excellent. The results of this rapid palliative therapy are quite comparable to those of more classical irradiation. Because of the very short survival of these patients, it would appear advantageous to treat them in as short a time interval as possible."}
{"id": "PMID:193599", "title": "[Intramammary spread of breast cancer].", "content": "At the conclusion of this study based on a careful histological analysis of 454 mastectomy specimens carried out at the Institut Gustave-Roussy between 1966 and 1971 it appears that 39 per cent of tumours which are neither central nor deep to the nipple have microscopic foci outside the main focus of tumour of which 24 per cent are at the level of the single nipple. The importance of these extensions is bound up with the size and histological type of the adenocarcinoma: pure intraduct and infiltrating lobular forms are accompanied frequently by microscopic intramammary foci at a distance (89% and 72%) the opposite of findings in the case of well differentiated and medullary forms. On the other hand no connection between the Scarff and Bloom grading is apparent except where the nipple only is involved. Finally there is a strong relationship between intramammary dissemination and regional lymph node metastases.", "contents": "[Intramammary spread of breast cancer]. At the conclusion of this study based on a careful histological analysis of 454 mastectomy specimens carried out at the Institut Gustave-Roussy between 1966 and 1971 it appears that 39 per cent of tumours which are neither central nor deep to the nipple have microscopic foci outside the main focus of tumour of which 24 per cent are at the level of the single nipple. The importance of these extensions is bound up with the size and histological type of the adenocarcinoma: pure intraduct and infiltrating lobular forms are accompanied frequently by microscopic intramammary foci at a distance (89% and 72%) the opposite of findings in the case of well differentiated and medullary forms. On the other hand no connection between the Scarff and Bloom grading is apparent except where the nipple only is involved. Finally there is a strong relationship between intramammary dissemination and regional lymph node metastases."}
{"id": "PMID:193602", "title": "Enteroviruses other than poliovirus.", "content": "The role of enteroviruses in certain specific disease--cardiac disease, nephritis, diabetes, and hemorrhagic conjunctivitis--is examined. It has now been well documented that Coxsackievirus B (types CB1 through CB5 but not CB6) is the main pathogen involved in various clinical forms of viral heart disease. Coxsackievirus A (CA4 and CA16) and echovirus (types 9 and 22) may also be associated with viral heart disease. In regard to the etiologic role of enteroviruses in nephritis, pancreatitis, and diabetes, again CBV, especially CB3 and CB4, has been suspected, but the data are controversial and further studies are needed. Hemorrhagic conjunctivitis, a newly observed clinical entity, is caused by enterovirus 70. It has spread to four continents (not including the Americas) in a pandemic fashion since 1969 and is now one of the common eye infections in these areas. The virus has some neurovirulence, and motor paralysis is known to occur as a complication; hence it should be carefully watched in the future.", "contents": "Enteroviruses other than poliovirus. The role of enteroviruses in certain specific disease--cardiac disease, nephritis, diabetes, and hemorrhagic conjunctivitis--is examined. It has now been well documented that Coxsackievirus B (types CB1 through CB5 but not CB6) is the main pathogen involved in various clinical forms of viral heart disease. Coxsackievirus A (CA4 and CA16) and echovirus (types 9 and 22) may also be associated with viral heart disease. In regard to the etiologic role of enteroviruses in nephritis, pancreatitis, and diabetes, again CBV, especially CB3 and CB4, has been suspected, but the data are controversial and further studies are needed. Hemorrhagic conjunctivitis, a newly observed clinical entity, is caused by enterovirus 70. It has spread to four continents (not including the Americas) in a pandemic fashion since 1969 and is now one of the common eye infections in these areas. The virus has some neurovirulence, and motor paralysis is known to occur as a complication; hence it should be carefully watched in the future."}
{"id": "PMID:193607", "title": "Blocked beds.", "content": "In a cross-sectional survey of 325 surgical and orthopaedic beds 43 (16%) of the 265 occupied beds were filled by patients who had no medical need to be in an acute ward. They had been in hospital for a median time of 40 weeks up to the survey date. Of the 43 patients, 11 were awaiting transfer to a geriatric ward; 13 to community residential care; and seven to their homes. There was no plan for discharge or transfer for the remaining 12 (28%). Those \"at risk\" of becoming long-stay patients for social reasons on these wards were women, over 75, living alone or with one relative, who had been admitted to hospital in emergency with a fractured femur, head injury, or other trauma. Action necessary to reduce the number of social long-stay patients includes (a) changing attitudes to the solving of social case problems; (b) revising procedures of assessment and planning of future care; (c) improving teamwork and record keeping within the hospital and the community services; (d) providing a better balance of acute, medium and long-stay hospital beds; and (e) putting more resources into rehabilitation.", "contents": "Blocked beds. In a cross-sectional survey of 325 surgical and orthopaedic beds 43 (16%) of the 265 occupied beds were filled by patients who had no medical need to be in an acute ward. They had been in hospital for a median time of 40 weeks up to the survey date. Of the 43 patients, 11 were awaiting transfer to a geriatric ward; 13 to community residential care; and seven to their homes. There was no plan for discharge or transfer for the remaining 12 (28%). Those \"at risk\" of becoming long-stay patients for social reasons on these wards were women, over 75, living alone or with one relative, who had been admitted to hospital in emergency with a fractured femur, head injury, or other trauma. Action necessary to reduce the number of social long-stay patients includes (a) changing attitudes to the solving of social case problems; (b) revising procedures of assessment and planning of future care; (c) improving teamwork and record keeping within the hospital and the community services; (d) providing a better balance of acute, medium and long-stay hospital beds; and (e) putting more resources into rehabilitation."}
{"id": "PMID:193610", "title": "The ultrastructural characteristics of the abnormal cytosomes in Batten-Kufs' disease.", "content": "Patients with Batten-Kufs' disease may be divided into three groups by electronmicroscopy of their storage deposits. In the first group, those characterized by curvilinear profiles, there is a strong correlation with a particular clinical syndrome, the late infantile form of the disease. In the second group, characterized by finger-print profiles, there is great diversity as to age and type of presentation. This is paralleled by diversity in the deposits. To the third group belongs the infantile form of the disease, as well as rare patients with later onset. Pathological diagnosis can be reliably, conveniently and consistently made from biopsy of skin by electronmicroscopy, and usually from biopsy of skeletal muscle as well.", "contents": "The ultrastructural characteristics of the abnormal cytosomes in Batten-Kufs' disease. Patients with Batten-Kufs' disease may be divided into three groups by electronmicroscopy of their storage deposits. In the first group, those characterized by curvilinear profiles, there is a strong correlation with a particular clinical syndrome, the late infantile form of the disease. In the second group, characterized by finger-print profiles, there is great diversity as to age and type of presentation. This is paralleled by diversity in the deposits. To the third group belongs the infantile form of the disease, as well as rare patients with later onset. Pathological diagnosis can be reliably, conveniently and consistently made from biopsy of skin by electronmicroscopy, and usually from biopsy of skeletal muscle as well."}
{"id": "PMID:193614", "title": "Isolation of glial cell-enriched and -depleted populations from mouse cerebellum by density gradient centrifugation and electronic cell sorting.", "content": "Preparative amounts of populations enriched and depleted in glial cells have been isolated from 10-day-old mouse cerebella. Discontinuous density bovine serum albumin (BSA) gradients provide two distinct populations: the one derived from the 10-15% BSA interface is enriched in cyclic nucleotide phosphohydrolase (CNPase) activity, and a percentage of S-100, GFA protein, and NS-1 antigen-positive cells; the other, located as the 15-31% interface, contains a cell population depleted in these compounds. This report also describes the first use of flow microfluorimetry and electronic cell sorting techniques for the analysis and isolation of cell populations derived from the mammalian central nervous system. Glial cell-enriched and -depleted populations obtained by BSA density gradient centrifugation were analyzed for their forward angle light scattering properties and their capacity to bind anti-corpus anti-serum to the cell surface. The glial cell-enriched fraction shows a different frequency distribution of light scattering than the glial-depleted fraction. Anti-corpus callosum antiserum binds preferentially to the glial cell-rich fraction. Cells can be sorted into corpus callosum antigen-positive and -negative cell fractions and recovered with a viability of more than 95% as judged by trypan blue exclusion. Anti-corpus callosum-positive sorted cells are enriched in CNPase activity, S-100, and glial fibrillary acidic proteins.", "contents": "Isolation of glial cell-enriched and -depleted populations from mouse cerebellum by density gradient centrifugation and electronic cell sorting. Preparative amounts of populations enriched and depleted in glial cells have been isolated from 10-day-old mouse cerebella. Discontinuous density bovine serum albumin (BSA) gradients provide two distinct populations: the one derived from the 10-15% BSA interface is enriched in cyclic nucleotide phosphohydrolase (CNPase) activity, and a percentage of S-100, GFA protein, and NS-1 antigen-positive cells; the other, located as the 15-31% interface, contains a cell population depleted in these compounds. This report also describes the first use of flow microfluorimetry and electronic cell sorting techniques for the analysis and isolation of cell populations derived from the mammalian central nervous system. Glial cell-enriched and -depleted populations obtained by BSA density gradient centrifugation were analyzed for their forward angle light scattering properties and their capacity to bind anti-corpus anti-serum to the cell surface. The glial cell-enriched fraction shows a different frequency distribution of light scattering than the glial-depleted fraction. Anti-corpus callosum antiserum binds preferentially to the glial cell-rich fraction. Cells can be sorted into corpus callosum antigen-positive and -negative cell fractions and recovered with a viability of more than 95% as judged by trypan blue exclusion. Anti-corpus callosum-positive sorted cells are enriched in CNPase activity, S-100, and glial fibrillary acidic proteins."}
{"id": "PMID:193620", "title": "[Cyto-immunological study of the Pleurodele pituitary gland].", "content": "In the pituitary of an Amphibian (Urodela), various cell types were localized by cytoimmunological techniques: corticotrophs located in a rostral zone near the median eminence, ventral orangeophilic cells secreting a prolactin-like hormone and erythrosinophilic cells in a more dorso-caudal situation secreting growth hormone. Alpha-MSH and beta-MSH produceng cell were identified in the intermediate lobe; these cells were also labelled with antibodies against 1-24 ACTH and 17-39 ACTH. These data are in accordance with results obtained after an experimental study of the prolactin cells.", "contents": "[Cyto-immunological study of the Pleurodele pituitary gland]. In the pituitary of an Amphibian (Urodela), various cell types were localized by cytoimmunological techniques: corticotrophs located in a rostral zone near the median eminence, ventral orangeophilic cells secreting a prolactin-like hormone and erythrosinophilic cells in a more dorso-caudal situation secreting growth hormone. Alpha-MSH and beta-MSH produceng cell were identified in the intermediate lobe; these cells were also labelled with antibodies against 1-24 ACTH and 17-39 ACTH. These data are in accordance with results obtained after an experimental study of the prolactin cells."}
{"id": "PMID:193616", "title": "Changes in CNS myelin proteins and glycoproteins after in situ autolysis.", "content": "The effects of postmortem autolysis in situ on myelin proteins and glycoproteins were studied in 25- and 125-day-old mouse brain and in adult bovine brainstem. In bovine myelin a loss of the major myelin glycoprotein was the only difference observed when the tissue was left at 19 degrees C for 24 hours compared to immediately frozen material. In the autolysed mouse brain, the myelin major glycoprotein was the most affected component with a 55% decrease. Both myelin basic protein components were degraded with a 35% loss. The other myelin proteins did not change under the conditions used for this study. There was also no change in the specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, a myelin-associated enzyme. Using the double labelling technique with [3H]fucose and [3 5S] sulfate as precursors injected intracranially, a shift of the major myelin glycoprotein labelled with radioactive sulfate towards a smaller apparent molecular size was observed as a result of the autolysis whereas the electrophoretic mobility of the fucose labelled major peak was unaffected.", "contents": "Changes in CNS myelin proteins and glycoproteins after in situ autolysis. The effects of postmortem autolysis in situ on myelin proteins and glycoproteins were studied in 25- and 125-day-old mouse brain and in adult bovine brainstem. In bovine myelin a loss of the major myelin glycoprotein was the only difference observed when the tissue was left at 19 degrees C for 24 hours compared to immediately frozen material. In the autolysed mouse brain, the myelin major glycoprotein was the most affected component with a 55% decrease. Both myelin basic protein components were degraded with a 35% loss. The other myelin proteins did not change under the conditions used for this study. There was also no change in the specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, a myelin-associated enzyme. Using the double labelling technique with [3H]fucose and [3 5S] sulfate as precursors injected intracranially, a shift of the major myelin glycoprotein labelled with radioactive sulfate towards a smaller apparent molecular size was observed as a result of the autolysis whereas the electrophoretic mobility of the fucose labelled major peak was unaffected."}
{"id": "PMID:193621", "title": "[Identification by immunofluorescence of various categories of anterior pituitary gland cells (somatotropin, prolactin, corticotropin, melanotropin, gonadotropin, and thyrotropin cells) in the spermophile (Citellus variegatus)].", "content": "Using antibodies against human STH, rat prolactin, 1-24, 17-39-synthetic ACTH, alpha- and beta-synthetic MSH, ovine LH, porcine LH beta, bovine TSH saturated with LH, it is possible to identify somatotropic, prolactin, corticotropic, melanotropic, gonadotropic and thyreotropic cells in the adenohypophysis of rodents Citellus variegatus and Graphiurus murinus. The topographical repartition and morphological characters of these cells are described.", "contents": "[Identification by immunofluorescence of various categories of anterior pituitary gland cells (somatotropin, prolactin, corticotropin, melanotropin, gonadotropin, and thyrotropin cells) in the spermophile (Citellus variegatus)]. Using antibodies against human STH, rat prolactin, 1-24, 17-39-synthetic ACTH, alpha- and beta-synthetic MSH, ovine LH, porcine LH beta, bovine TSH saturated with LH, it is possible to identify somatotropic, prolactin, corticotropic, melanotropic, gonadotropic and thyreotropic cells in the adenohypophysis of rodents Citellus variegatus and Graphiurus murinus. The topographical repartition and morphological characters of these cells are described."}
{"id": "PMID:193622", "title": "Field trial evaluation of a reo-coronavirus calf diarrhea vaccine.", "content": "Field trials were conducted using an experimental, modified live virus, oral vaccine for prevention of reo- and coronavirus calf diarrhea. Prior to the trials, one or both of the specific causative agents were identified from affected calves in each participating herd. In 21 herds, sequential trials were conducted in which results of uninterrupted vaccination were compared with disease rates during a preceding or subsequent control period. In these herds there was a statistically significant reduction in the morbidity and mortality from disease in 1,598 vaccinates compared with the rates in 829 prevaccination control calves. Morbidity and mortality in 206 post-vaccination control calves rose marginally above the rates in the same vaccinates. In 26 other herds, where double blind trials were conducted, rates of morbidity and mortality from disease were virtually the same for 1,080 vaccinated calves and 355 placebo calves. Vaccinates in the sequential trials had the lowest morbidity and mortality rates of any test group in either field trial format. In a selected dairy herd, both field trial formats were implemented and the results compared. In the double blind trial, vaccinates and placebo calves had comparable rates of morbidity and mortality from disease. When a sequential trial was later implemented, a statistically significant reduction in morbidity and mortality occurred in vaccinates compared with rates in control calves.", "contents": "Field trial evaluation of a reo-coronavirus calf diarrhea vaccine. Field trials were conducted using an experimental, modified live virus, oral vaccine for prevention of reo- and coronavirus calf diarrhea. Prior to the trials, one or both of the specific causative agents were identified from affected calves in each participating herd. In 21 herds, sequential trials were conducted in which results of uninterrupted vaccination were compared with disease rates during a preceding or subsequent control period. In these herds there was a statistically significant reduction in the morbidity and mortality from disease in 1,598 vaccinates compared with the rates in 829 prevaccination control calves. Morbidity and mortality in 206 post-vaccination control calves rose marginally above the rates in the same vaccinates. In 26 other herds, where double blind trials were conducted, rates of morbidity and mortality from disease were virtually the same for 1,080 vaccinated calves and 355 placebo calves. Vaccinates in the sequential trials had the lowest morbidity and mortality rates of any test group in either field trial format. In a selected dairy herd, both field trial formats were implemented and the results compared. In the double blind trial, vaccinates and placebo calves had comparable rates of morbidity and mortality from disease. When a sequential trial was later implemented, a statistically significant reduction in morbidity and mortality occurred in vaccinates compared with rates in control calves."}
{"id": "PMID:193623", "title": "An outbreak of infectious laryngotracheitis in commercial poultry flocks in Ontario.", "content": "An outbreak of infectious laryngotracheitis was observed in Ontario commercial poultry flocks from September 1974 to June 1975. Fifty-five flocks, totalling over 848,770 birds were clinically affected by this disease in the southern region of the province. Sixty-nine percent (38/55) of the exposed flocks were in Wentworth country and the regional municipality of Niagara. Hemorrhagic tracheitis with histological evidence of intranuclear inclusion bodies in syncytia of tracheal epithelial cells were the salient pathological findings.", "contents": "An outbreak of infectious laryngotracheitis in commercial poultry flocks in Ontario. An outbreak of infectious laryngotracheitis was observed in Ontario commercial poultry flocks from September 1974 to June 1975. Fifty-five flocks, totalling over 848,770 birds were clinically affected by this disease in the southern region of the province. Sixty-nine percent (38/55) of the exposed flocks were in Wentworth country and the regional municipality of Niagara. Hemorrhagic tracheitis with histological evidence of intranuclear inclusion bodies in syncytia of tracheal epithelial cells were the salient pathological findings."}
{"id": "PMID:193624", "title": "Neutralizing activity in the gastrointestinal contents of piglets vaccinated with an ethylenimine-inactivated porcine enterovirus.", "content": "The T80 strain of porcine enterovirus was rapidly and completely inactiviated by ethylenimine in a reaction which appeared to follow first order kinetics. The virus was effectively concentrated 35- to 88-fold, with recovery rates of 23 t0 53%, by adsorption to the polyelectrolyte PE60. Multiple doses of adjuvanted, PE60-concentrated, ethylenimine-inactivated T80 virus given by both the oral and subcutaneous routes induced the appearance of significant levels of virus neutralizing activity in the gastrointestinal tract of piglets vaccinated at four weeks of age. This activity, found predominantly in large intestine, was present 14 days after administration of the first dose of vaccine and significant levels of activity were still detectable six weeks later. Titres of serum virus neutralizing activity were higher and more persistent than in piglets which received live or formaldehyde-inactivated T80 virus by the oral or intramuscular routes.", "contents": "Neutralizing activity in the gastrointestinal contents of piglets vaccinated with an ethylenimine-inactivated porcine enterovirus. The T80 strain of porcine enterovirus was rapidly and completely inactiviated by ethylenimine in a reaction which appeared to follow first order kinetics. The virus was effectively concentrated 35- to 88-fold, with recovery rates of 23 t0 53%, by adsorption to the polyelectrolyte PE60. Multiple doses of adjuvanted, PE60-concentrated, ethylenimine-inactivated T80 virus given by both the oral and subcutaneous routes induced the appearance of significant levels of virus neutralizing activity in the gastrointestinal tract of piglets vaccinated at four weeks of age. This activity, found predominantly in large intestine, was present 14 days after administration of the first dose of vaccine and significant levels of activity were still detectable six weeks later. Titres of serum virus neutralizing activity were higher and more persistent than in piglets which received live or formaldehyde-inactivated T80 virus by the oral or intramuscular routes."}
{"id": "PMID:193625", "title": "Demonstration of heavy and light density populations of Aleutian disease virus.", "content": "A highly purified and concentrated suspension of aleutian disease virus was prepared from large quantities of early infected mink tissues using repeated fluorocarbon extraction procedures. Equilibrium centrifugation of the aleutian disease virus preparation in a cesium chloride gradient yielded three distinct bands at buoyant densities of 1.295, 1.332, and 1.405--1.416 g/cm(3). Electron microscopic observations of these three bands revealed mainly empty particles in the first band. In the second band complete particles with a flattened appearnce predominated and there were also some empty particles. In the third band both complete and empty particles were observed. The size of the aleutian disease virus particles observed in all of the three densities was 23 nm. Light aleutian disease virions (density of 1.332 g/cm3) had a particle to counterimmunoelectrophoresis antigen ratio comparable to that of dense aleutian disease virions (density of 1.405--1.416 g/cm3) but possessed much lower infectivity as determined by mink inoculation.", "contents": "Demonstration of heavy and light density populations of Aleutian disease virus. A highly purified and concentrated suspension of aleutian disease virus was prepared from large quantities of early infected mink tissues using repeated fluorocarbon extraction procedures. Equilibrium centrifugation of the aleutian disease virus preparation in a cesium chloride gradient yielded three distinct bands at buoyant densities of 1.295, 1.332, and 1.405--1.416 g/cm(3). Electron microscopic observations of these three bands revealed mainly empty particles in the first band. In the second band complete particles with a flattened appearnce predominated and there were also some empty particles. In the third band both complete and empty particles were observed. The size of the aleutian disease virus particles observed in all of the three densities was 23 nm. Light aleutian disease virions (density of 1.332 g/cm3) had a particle to counterimmunoelectrophoresis antigen ratio comparable to that of dense aleutian disease virions (density of 1.405--1.416 g/cm3) but possessed much lower infectivity as determined by mink inoculation."}
{"id": "PMID:193626", "title": "The significance of cAMP induced alterations in the cellular structure of Phycomyces.", "content": "Effect of cyclic AMP (cAMP) on Phycomyces blakesleeanus was studied by growing sporangiospores on glucose-asparagine agar or liquid medium containing three different levels of cAMP (10, 20 and 40 micronM) in addition to the control (no cAMP added). The response of Phycomyces to the exogenous cAMP concentration in the medium is as follows: (1) the time required for germ tube emergence is reduced; (2) the diameter of the mycelium is increased (sometimes more than 10 times) and frequency of branching is also increased; (3) the cell wall of the mycelium is thickened (in some cases more than 5 times); (4) the glycogen in the cytoplasm is decreased as visualized in thin sections and also demonstrated in biochemical quantitation; and (5) the distribution of intercalated membranous particles (Imp) on plasma membrane is altered and this can be easily detected in freeze-fractured replica. Such a change in Imp is seen in the formation of small clusters of aggregated particles on the plasmic half (PF) and craters on the complementary exoplasmic half (EF) of the plasma membrane. Although the mechanism of cAMP action requires further exploration, it is possible that the addition of cAMP to the culture medium leads to degradation of glycogen and enhancement of chitin synthesis since the cell wall is largely composed of chitin. The alteration in Imp may be related to a change in the activity of chitin synthetase which is a plasma membrane-bound enzyme.", "contents": "The significance of cAMP induced alterations in the cellular structure of Phycomyces. Effect of cyclic AMP (cAMP) on Phycomyces blakesleeanus was studied by growing sporangiospores on glucose-asparagine agar or liquid medium containing three different levels of cAMP (10, 20 and 40 micronM) in addition to the control (no cAMP added). The response of Phycomyces to the exogenous cAMP concentration in the medium is as follows: (1) the time required for germ tube emergence is reduced; (2) the diameter of the mycelium is increased (sometimes more than 10 times) and frequency of branching is also increased; (3) the cell wall of the mycelium is thickened (in some cases more than 5 times); (4) the glycogen in the cytoplasm is decreased as visualized in thin sections and also demonstrated in biochemical quantitation; and (5) the distribution of intercalated membranous particles (Imp) on plasma membrane is altered and this can be easily detected in freeze-fractured replica. Such a change in Imp is seen in the formation of small clusters of aggregated particles on the plasmic half (PF) and craters on the complementary exoplasmic half (EF) of the plasma membrane. Although the mechanism of cAMP action requires further exploration, it is possible that the addition of cAMP to the culture medium leads to degradation of glycogen and enhancement of chitin synthesis since the cell wall is largely composed of chitin. The alteration in Imp may be related to a change in the activity of chitin synthetase which is a plasma membrane-bound enzyme."}
{"id": "PMID:193628", "title": "The effect of N-nitrosobis(2-oxopropyl)amine after oral administration to hamsters.", "content": "Oral administration of N-nitrosobis(2-oxopropyl)amine (BOP) in drinking water to Syrian golden hamsters for 90 days resulted in a high incidence of intra- and extrahepatic bile duct neoplasms. Only a few pancreatic neoplasms and no lung and kidney tumors developed, in contrast to results obtained after subcutaneous BOP administration.", "contents": "The effect of N-nitrosobis(2-oxopropyl)amine after oral administration to hamsters. Oral administration of N-nitrosobis(2-oxopropyl)amine (BOP) in drinking water to Syrian golden hamsters for 90 days resulted in a high incidence of intra- and extrahepatic bile duct neoplasms. Only a few pancreatic neoplasms and no lung and kidney tumors developed, in contrast to results obtained after subcutaneous BOP administration."}
{"id": "PMID:193629", "title": "Presence of ribonucleotide sequences complementary to Rous sarcoma virus (RSV) RNA in chicken cells infected with RSV.", "content": "RNA--RNA molecular hybridization between [125I] RNA from Rous sarcoma virus virions and RNAs isolated from various subcellular fractions, i.e. nuclei, mitochondria, free and membrane-bound polyribosomes, from tumors induced by RSV in chickens resulted in the formation of RNAase-resistant hybrids only with the RNA of mitochondria and membrane-bound polysomes. The origin of complementary regions in the RNAs from these organelles is discussed.", "contents": "Presence of ribonucleotide sequences complementary to Rous sarcoma virus (RSV) RNA in chicken cells infected with RSV. RNA--RNA molecular hybridization between [125I] RNA from Rous sarcoma virus virions and RNAs isolated from various subcellular fractions, i.e. nuclei, mitochondria, free and membrane-bound polyribosomes, from tumors induced by RSV in chickens resulted in the formation of RNAase-resistant hybrids only with the RNA of mitochondria and membrane-bound polysomes. The origin of complementary regions in the RNAs from these organelles is discussed."}
{"id": "PMID:193630", "title": "Hormone binding by human mammary carcinoma.", "content": "The specific binding of labeled porcine insulin, human prolactin, and human growth hormone was studied in 63 human breast tumors and 15 nonmalignant breast tissues. Most (90%) of the tumors demonstrated significant binding of insulin, as did 80% of nonmalignant tissues. Autoradiographic studies indicated that insulin bound dominantly to tumor cells, rather than to fat and fibrous tissue contained within tumors. Specific binding of prolactin and growth hormone of greater than 1% was seen in 20 and 12% of tumors, respectively, and one tumor studied in detail showed a small amount of saturable, high-affinity prolactin binding. The affinity of binding of insulin and prolactin to tumor was similar to that seen in target tissues in subprimate species (Kd = 4 X 10(-10) M), but the prolactin-binding capacity in the one tumor studied in detail was very low (10 fmoles/mg membrane protein), compared with prolactin-responsive experimental mammary carcinoma.", "contents": "Hormone binding by human mammary carcinoma. The specific binding of labeled porcine insulin, human prolactin, and human growth hormone was studied in 63 human breast tumors and 15 nonmalignant breast tissues. Most (90%) of the tumors demonstrated significant binding of insulin, as did 80% of nonmalignant tissues. Autoradiographic studies indicated that insulin bound dominantly to tumor cells, rather than to fat and fibrous tissue contained within tumors. Specific binding of prolactin and growth hormone of greater than 1% was seen in 20 and 12% of tumors, respectively, and one tumor studied in detail showed a small amount of saturable, high-affinity prolactin binding. The affinity of binding of insulin and prolactin to tumor was similar to that seen in target tissues in subprimate species (Kd = 4 X 10(-10) M), but the prolactin-binding capacity in the one tumor studied in detail was very low (10 fmoles/mg membrane protein), compared with prolactin-responsive experimental mammary carcinoma."}
{"id": "PMID:193632", "title": "Levels of mammary tumor virus in hormone-dependent and -independent mouse mammary tumor cells.", "content": "Levels of mammary tumor virus particles (types A and B) and levels of the virus antigen were assayed in hormone-dependent and -independent mammary tumors of GR mice. Various transplant generations of seven separate tumor lines were investigated. The results indicated that the tumors consisted of different cell clones, each of which exhibited a separate progressive expression and subsequent loss of the mammary tumor virus. When the tumors were transplanted, levels of B particles first declined in the hormone-dependent cells, but in later transplant generations, the B particle content of the autonomous cells also dropped. In some tumor lines, this was accompanied by a decrease in viral antigens and/or A particles, but in other lines these concentrations remained high. One tumor line (line V) that remained hormone-dependent throughout nine transplantations was practically devoid of B particles but contained high levels of A particles and mammary tumor antigen.", "contents": "Levels of mammary tumor virus in hormone-dependent and -independent mouse mammary tumor cells. Levels of mammary tumor virus particles (types A and B) and levels of the virus antigen were assayed in hormone-dependent and -independent mammary tumors of GR mice. Various transplant generations of seven separate tumor lines were investigated. The results indicated that the tumors consisted of different cell clones, each of which exhibited a separate progressive expression and subsequent loss of the mammary tumor virus. When the tumors were transplanted, levels of B particles first declined in the hormone-dependent cells, but in later transplant generations, the B particle content of the autonomous cells also dropped. In some tumor lines, this was accompanied by a decrease in viral antigens and/or A particles, but in other lines these concentrations remained high. One tumor line (line V) that remained hormone-dependent throughout nine transplantations was practically devoid of B particles but contained high levels of A particles and mammary tumor antigen."}
{"id": "PMID:193633", "title": "Immunoelectron microscopic studies of antibodies in mouse sera directed against mouse mammary tumor virus.", "content": "Indirect immunoferritin and fixed immunofluorescence tests were carried out on (a) sera of mice hyperimmunized with isologous mouse mammary tumor virus (MMTV) particles or isologous MMTV-producing mammary tumor cells grown in tissue culture and (b) sera of mammary tumor-bearing and tumor-free mice of several inbred strains. Sera were tested against MMTV produced by C3H/HEJ/Tex tissue culture cells (MMT-1). Mammary tumor-bearing A/Dm, C3H/HeTex, and RIII/Dm mice and apparently tumor-free A/Dm mice were found to develop naturally occurring nonprotective anti-MMTV antibodies, whereas sera of tumor-free C3H/HeTex, RIII/Dm, and C57BL/6/Tex female mice and A/Dm, C3H/HeTex, and RIII/Dm male mice did not contain anti-MMTV antibodies. Indirect immunoferritin and fixed immunofluorescence labeling of MMTV particles was prevented by absorbing sera with purified MMTV particles. The results demonstrate the relationship of naturally occurring anti-MMTV antibodies in mouse sera to the presence of mammary tumors, confirm previous reports that mice are not tolerant to MMTV, and further establish the usefulness of the indirect immunoferritin procedure in studies of the immune response of mice.", "contents": "Immunoelectron microscopic studies of antibodies in mouse sera directed against mouse mammary tumor virus. Indirect immunoferritin and fixed immunofluorescence tests were carried out on (a) sera of mice hyperimmunized with isologous mouse mammary tumor virus (MMTV) particles or isologous MMTV-producing mammary tumor cells grown in tissue culture and (b) sera of mammary tumor-bearing and tumor-free mice of several inbred strains. Sera were tested against MMTV produced by C3H/HEJ/Tex tissue culture cells (MMT-1). Mammary tumor-bearing A/Dm, C3H/HeTex, and RIII/Dm mice and apparently tumor-free A/Dm mice were found to develop naturally occurring nonprotective anti-MMTV antibodies, whereas sera of tumor-free C3H/HeTex, RIII/Dm, and C57BL/6/Tex female mice and A/Dm, C3H/HeTex, and RIII/Dm male mice did not contain anti-MMTV antibodies. Indirect immunoferritin and fixed immunofluorescence labeling of MMTV particles was prevented by absorbing sera with purified MMTV particles. The results demonstrate the relationship of naturally occurring anti-MMTV antibodies in mouse sera to the presence of mammary tumors, confirm previous reports that mice are not tolerant to MMTV, and further establish the usefulness of the indirect immunoferritin procedure in studies of the immune response of mice."}
{"id": "PMID:193636", "title": "Alterations in glycosphingolipids of plasma membranes from Morris hepatoma 5123TC.", "content": "Neutral glycosphingolipids and gangliosides were quantified in lipid extracts from normal rat liver and Morris hepatoma 5123TC and their isolated plasma membranes to determine differences in these components in the cell surface membranes of malignant cells. Glycosphingolipids present in rat liver and hepatoma were concentrated in plasma membranes, and glycosphingolipid patterns in plasma membranes reflected those of their respective whole cells. Neutral glycospingolipids of plasma membranes from normal liver and from hepatoma consisted of ceramide mono- and dihexosides, together accounting for 83 to 86% of the total neutral glycosphingolipids and some ceramide tri- and tetrahexosides. In plasma membranes from hepatoma, the concentration of neutral glycosphingolipids was generally greater than in plasma membranes from normal liver. Gangliosides of plasma membranes from hepatoma were altered more drastically, since trisialogangliosides, present in plasma membranes from normal liver, were absent, while hematosides, monosialogangliosides, and disialogangliosides were increased an average eight-fold. These data are compatible with a concept of incomplete synthesis of trisialogangliosides in hepatoma and an accumulation precursor gangliosides.", "contents": "Alterations in glycosphingolipids of plasma membranes from Morris hepatoma 5123TC. Neutral glycosphingolipids and gangliosides were quantified in lipid extracts from normal rat liver and Morris hepatoma 5123TC and their isolated plasma membranes to determine differences in these components in the cell surface membranes of malignant cells. Glycosphingolipids present in rat liver and hepatoma were concentrated in plasma membranes, and glycosphingolipid patterns in plasma membranes reflected those of their respective whole cells. Neutral glycospingolipids of plasma membranes from normal liver and from hepatoma consisted of ceramide mono- and dihexosides, together accounting for 83 to 86% of the total neutral glycosphingolipids and some ceramide tri- and tetrahexosides. In plasma membranes from hepatoma, the concentration of neutral glycosphingolipids was generally greater than in plasma membranes from normal liver. Gangliosides of plasma membranes from hepatoma were altered more drastically, since trisialogangliosides, present in plasma membranes from normal liver, were absent, while hematosides, monosialogangliosides, and disialogangliosides were increased an average eight-fold. These data are compatible with a concept of incomplete synthesis of trisialogangliosides in hepatoma and an accumulation precursor gangliosides."}
{"id": "PMID:193637", "title": "Mechanism of action of inosine dialdehyde (NSC 118994) in the inhibition of proliferation of tumor cells in culture.", "content": "Inosine dialdehyde (INOX), the periodate oxidation product of inosine, inhibited the proliferation of various tumor cell lines in suspension culture in a concentration-dependent manner. A concentration of about 1 mM was required to completely inhibit the proliferation of Novikoff rat hepatoma and mouse L-cells, whereas about 0.1 mM completely inhibited the proliferation of L1210 and P388 mouse leukemia and Chinese hamster ovary cells. INOX inhibited in a similar time- and concentration-dependent manner the synthesis of protein, RNA, and DNA, as measured by the incorporation of labeled amino acid, uridine, and thymidine, into acid-insoluble material, without significantly affecting the incorporation of these precursors into the acid-soluble pool. Flow microfluorometric analyses showed that many of the INOX-treated cells became arrested in G2 + M. The results are consistent with the view that INOX affects multiple metabolic steps. The effects of INOX were quite different from those caused  by typical inhibitors of ribonucleotide reductase, hydroxyurea, and 2,3-dihydro-1H-pyrazolo(2,3-a)imidazole, which very rapidly inhibited DNA synthesis and caused arrest of the cells in G1, with minimal effects on RNA and protein synthesis.", "contents": "Mechanism of action of inosine dialdehyde (NSC 118994) in the inhibition of proliferation of tumor cells in culture. Inosine dialdehyde (INOX), the periodate oxidation product of inosine, inhibited the proliferation of various tumor cell lines in suspension culture in a concentration-dependent manner. A concentration of about 1 mM was required to completely inhibit the proliferation of Novikoff rat hepatoma and mouse L-cells, whereas about 0.1 mM completely inhibited the proliferation of L1210 and P388 mouse leukemia and Chinese hamster ovary cells. INOX inhibited in a similar time- and concentration-dependent manner the synthesis of protein, RNA, and DNA, as measured by the incorporation of labeled amino acid, uridine, and thymidine, into acid-insoluble material, without significantly affecting the incorporation of these precursors into the acid-soluble pool. Flow microfluorometric analyses showed that many of the INOX-treated cells became arrested in G2 + M. The results are consistent with the view that INOX affects multiple metabolic steps. The effects of INOX were quite different from those caused  by typical inhibitors of ribonucleotide reductase, hydroxyurea, and 2,3-dihydro-1H-pyrazolo(2,3-a)imidazole, which very rapidly inhibited DNA synthesis and caused arrest of the cells in G1, with minimal effects on RNA and protein synthesis."}
{"id": "PMID:193638", "title": "Mutagenicity of cancer chemotherapeutic agents in the Salmonella/microsome test.", "content": "Seventeen cancer chemotherapeutic agents were tested for their ability to mutate Salmonella typhimurium tester strains in the Salmonella/microsome mutagenicity test. There was a high correlation between the mutagenicity and carcinogenicity of a given agent. Carcinogens positive in the test were Adriamycin, daunomycin, 1-propanol-3,3'-iminodimethanesulfonate, cyclophosphamide, isophosphamide, hycanthone, chlornaphazin, nitrogen mustard, uracil mustard, melphalan, and thio-tepa. Two carcinogesn, actinomycin D and bleomycin, were not detected as mutagens. The presumptive noncarcinogen, methotrexate, was negative in the test. Tilorone and 6-mercaptopurine, tentatively classified as noncarcinogens, were mutagenic. The carcinogenicity of cis-dichlorodiammineplatinum(II), which was positive in the test, has not been determined.", "contents": "Mutagenicity of cancer chemotherapeutic agents in the Salmonella/microsome test. Seventeen cancer chemotherapeutic agents were tested for their ability to mutate Salmonella typhimurium tester strains in the Salmonella/microsome mutagenicity test. There was a high correlation between the mutagenicity and carcinogenicity of a given agent. Carcinogens positive in the test were Adriamycin, daunomycin, 1-propanol-3,3'-iminodimethanesulfonate, cyclophosphamide, isophosphamide, hycanthone, chlornaphazin, nitrogen mustard, uracil mustard, melphalan, and thio-tepa. Two carcinogesn, actinomycin D and bleomycin, were not detected as mutagens. The presumptive noncarcinogen, methotrexate, was negative in the test. Tilorone and 6-mercaptopurine, tentatively classified as noncarcinogens, were mutagenic. The carcinogenicity of cis-dichlorodiammineplatinum(II), which was positive in the test, has not been determined."}
{"id": "PMID:193640", "title": "Occurrence of steroid glucuronyltransferases in a hepatoma.", "content": "Occurrence of estrone, estradiol, and testosterone glucuronyltranferase activities was tested in a well-differentiated hepatoma, Reuber H35. Transferase activities for estrone and estradiol were found in the hepatoma. The Michaelis-Menten kinetics of these two microsomal glucuronyltransferase activities were similar in hepatoma and in liver preparations, except for a somewhat higher apparent Km for estradiol in the hepatoma preparations. Under the same experimental conditions, only trace amounts of testosterone glucuronyltransferase activity could be detected in the hepatoma preparations. By contrast, in liver microsomal preparations, testosterone glucuronyltransferase activity was the highest among the steroid glucuronyltransferase activities tested.", "contents": "Occurrence of steroid glucuronyltransferases in a hepatoma. Occurrence of estrone, estradiol, and testosterone glucuronyltranferase activities was tested in a well-differentiated hepatoma, Reuber H35. Transferase activities for estrone and estradiol were found in the hepatoma. The Michaelis-Menten kinetics of these two microsomal glucuronyltransferase activities were similar in hepatoma and in liver preparations, except for a somewhat higher apparent Km for estradiol in the hepatoma preparations. Under the same experimental conditions, only trace amounts of testosterone glucuronyltransferase activity could be detected in the hepatoma preparations. By contrast, in liver microsomal preparations, testosterone glucuronyltransferase activity was the highest among the steroid glucuronyltransferase activities tested."}
{"id": "PMID:193641", "title": "Cell surface markers on epithelial-Burkitt hybrid cells superinfected with Epstein-Barr virus.", "content": "Attempts were made to superinfect two epithelial-Burkitt hybrid cell lines, designated D98/HR-1 and D98/Raji, with Epstein-Barr virus (EBV) and to investigate the expression of some cell surfacr markers including histocompatibility antigens, and the presence of B-cell markers, such as receptors for the third complement component and for monkey red blood cells. Successful superinfection of D98/HR-1 cells with EBV was made evident by the expression of early antigen and, to a lesser extent, virus capsid antigen. Only a rare D98/Raji cell was found to be positive for early antigen. The histocompatibility antigens of the parental cell lines D98, HR-1, and Raji were expressed on the surfaces of the hybrid cells. Receptors for third complement components b and d were not detected on the hybrid cells or on the D98P OR HR-1 cell lines; they were found, however, on the Raji cells, indicating that EBV receptors and complement receptors can be separated. The significance of the infection of the hybrid cells with EBV and the expression of cell surface markers is described.", "contents": "Cell surface markers on epithelial-Burkitt hybrid cells superinfected with Epstein-Barr virus. Attempts were made to superinfect two epithelial-Burkitt hybrid cell lines, designated D98/HR-1 and D98/Raji, with Epstein-Barr virus (EBV) and to investigate the expression of some cell surfacr markers including histocompatibility antigens, and the presence of B-cell markers, such as receptors for the third complement component and for monkey red blood cells. Successful superinfection of D98/HR-1 cells with EBV was made evident by the expression of early antigen and, to a lesser extent, virus capsid antigen. Only a rare D98/Raji cell was found to be positive for early antigen. The histocompatibility antigens of the parental cell lines D98, HR-1, and Raji were expressed on the surfaces of the hybrid cells. Receptors for third complement components b and d were not detected on the hybrid cells or on the D98P OR HR-1 cell lines; they were found, however, on the Raji cells, indicating that EBV receptors and complement receptors can be separated. The significance of the infection of the hybrid cells with EBV and the expression of cell surface markers is described."}
{"id": "PMID:193643", "title": "[Structure of periodated ribonucleosides and ribonucleotides].", "content": "Periodate oxidation converted adenosine, guanosine, cytidine, and uridine into the corresponding dialdehydes. No free dialdehydes are present in solution, but several hydrated species occur (i.r. and n.m.r.). In the solid state, the dialdehydes are completely polymerized. The m.s. molecular peaks corresponding to the free daildehydes were of very low intensity. The c.d spectra of adenosine- and cytidinedialdehyde showed heavily diminished Cotton effects in comparison to the parent nucleosides. For uridine-dialdehyde, the signal intensity of the strongest transition was diminished by about one half, indicating a looser structure allowing free rotation of the base. By contrast, the c.d. signal of guanosine-dialdehyde was increased, indicating self-association of oligomers. The nucleoside-dialdehydes gave, with hydrazides, morpholine derivatives, which posses rigid, stable structures (c.d).", "contents": "[Structure of periodated ribonucleosides and ribonucleotides]. Periodate oxidation converted adenosine, guanosine, cytidine, and uridine into the corresponding dialdehydes. No free dialdehydes are present in solution, but several hydrated species occur (i.r. and n.m.r.). In the solid state, the dialdehydes are completely polymerized. The m.s. molecular peaks corresponding to the free daildehydes were of very low intensity. The c.d spectra of adenosine- and cytidinedialdehyde showed heavily diminished Cotton effects in comparison to the parent nucleosides. For uridine-dialdehyde, the signal intensity of the strongest transition was diminished by about one half, indicating a looser structure allowing free rotation of the base. By contrast, the c.d. signal of guanosine-dialdehyde was increased, indicating self-association of oligomers. The nucleoside-dialdehydes gave, with hydrazides, morpholine derivatives, which posses rigid, stable structures (c.d)."}
{"id": "PMID:193642", "title": "Combined modality treatment for oat cell carcinoma of the lung: a randomized trial 1,2,3.", "content": "Twenty-three patients with oat cell cancer of the lung were randomized to receive chemotherapy with POCC (procarbazine, 100 mg/m2/day orally, Days 1-14; vincristine, 2 mg iv, Days 1 and 8; cyclophosphamide, 600 mg/m2 iv, Days 1 and 8; and CCNU, 60 mg/m2 orally, Day 1) or COM (cyclophosphamide, 2000 mg/m2 iv, Day 1; vincristine, 2 mg iv, Day 1; and methotrexate, 30 mg/m2 iv, Day 15). After two to three cycles of chemotherapy, all patients were to receive radiotherapy to initially involved sites and then have chemotherapy continued. Patients treated with POCC had a median survival of 14 months vs 10 months for those treated with COM (P = 0.055). Eight of 15 first sites of relapse were intrathoracic and five of these eight had received radiotherapy to that site. Six central nervous system (CNS) failures were evenly divided between the two chemotherapy programs. Thus, the CNS penetration of procarbazine and CCNU in the POCC combination did not prevent CNS relapse. All future patients will receive prophylactic brain radiotherapy.", "contents": "Combined modality treatment for oat cell carcinoma of the lung: a randomized trial 1,2,3. Twenty-three patients with oat cell cancer of the lung were randomized to receive chemotherapy with POCC (procarbazine, 100 mg/m2/day orally, Days 1-14; vincristine, 2 mg iv, Days 1 and 8; cyclophosphamide, 600 mg/m2 iv, Days 1 and 8; and CCNU, 60 mg/m2 orally, Day 1) or COM (cyclophosphamide, 2000 mg/m2 iv, Day 1; vincristine, 2 mg iv, Day 1; and methotrexate, 30 mg/m2 iv, Day 15). After two to three cycles of chemotherapy, all patients were to receive radiotherapy to initially involved sites and then have chemotherapy continued. Patients treated with POCC had a median survival of 14 months vs 10 months for those treated with COM (P = 0.055). Eight of 15 first sites of relapse were intrathoracic and five of these eight had received radiotherapy to that site. Six central nervous system (CNS) failures were evenly divided between the two chemotherapy programs. Thus, the CNS penetration of procarbazine and CCNU in the POCC combination did not prevent CNS relapse. All future patients will receive prophylactic brain radiotherapy."}
{"id": "PMID:193645", "title": "Structural investigation of Klebsiella serotype K36 polysaccharide.", "content": "Klebsiella D36 capsular polysaccharide has been investigated by methylation, Smith-periodate oxidation and partial hydrolysis techniques. The structure was found to consist of a hexasaccharide repeating unit as shown. The anomeric configurations of the sugar residues were determined by 1H and 13Cn.m.r.spectroscopy on isolated oligomers obtained during the degradative studies and on the intact polysaccharide.", "contents": "Structural investigation of Klebsiella serotype K36 polysaccharide. Klebsiella D36 capsular polysaccharide has been investigated by methylation, Smith-periodate oxidation and partial hydrolysis techniques. The structure was found to consist of a hexasaccharide repeating unit as shown. The anomeric configurations of the sugar residues were determined by 1H and 13Cn.m.r.spectroscopy on isolated oligomers obtained during the degradative studies and on the intact polysaccharide."}
{"id": "PMID:193646", "title": "Chicken macrochromosomes contain an endogenous provirus and microchromosomes contain sequences related to the transforming gene of ASV.", "content": "Chicken chromosomes from a euploid Marek's lymphoma cell line have been partially fractionated according to size by rate zonal centrifugation in a zonal rotor. DNA-DNA hybridization tests, using unlabeled DNA extracted from gradient fractions and labeled single-stranded, virus-specific DNAs prepared in vitro, indicate that large macrochromosomes harbor the provirus for the endogenous RNA tumor virus of chickens (RAVO), whereas a cellular sequence related to the transforming gene of avian sarcoma virus (ASV) is located in microchromosomes. In support of the method, we have also shown that the single gene for ovalbumin can be assigned to macrochromosomes.", "contents": "Chicken macrochromosomes contain an endogenous provirus and microchromosomes contain sequences related to the transforming gene of ASV. Chicken chromosomes from a euploid Marek's lymphoma cell line have been partially fractionated according to size by rate zonal centrifugation in a zonal rotor. DNA-DNA hybridization tests, using unlabeled DNA extracted from gradient fractions and labeled single-stranded, virus-specific DNAs prepared in vitro, indicate that large macrochromosomes harbor the provirus for the endogenous RNA tumor virus of chickens (RAVO), whereas a cellular sequence related to the transforming gene of avian sarcoma virus (ASV) is located in microchromosomes. In support of the method, we have also shown that the single gene for ovalbumin can be assigned to macrochromosomes."}
{"id": "PMID:193650", "title": "Alkylation of cytosine and 5-hydroxymethyl-cytosine by methyl methanesulphonate and N-methyl-N-nitrosourea: its relevance to mutagenesis.", "content": "The reaction of cytosine and 5-hydroxymethyl-cytosine (OHMeCyt) with a variety of monofunctional alkylating agents has been investigated to evaluate further the possible role of cytosine alkylation in mutagenesis and the possibility that the immunity of T-even phages to mutation by methyl methanesulphonate (MMS) was due to the unreactivity of OHMeCyt towards this agent. Both cytosine and OHMeCyt reacted equally well with the methylating agents MMS and N-methyl-N-nitrosourea (MNU) affording 6% and less than 1% respectively of the 3-substituted derivative. No product was isolated following subjection of the bases to reaction with ethyl methane-sulphonate (EMS), N-ethyl-N-nitrosourea (ENU) or iso-propyl methane-sulphonate (iPMS).", "contents": "Alkylation of cytosine and 5-hydroxymethyl-cytosine by methyl methanesulphonate and N-methyl-N-nitrosourea: its relevance to mutagenesis. The reaction of cytosine and 5-hydroxymethyl-cytosine (OHMeCyt) with a variety of monofunctional alkylating agents has been investigated to evaluate further the possible role of cytosine alkylation in mutagenesis and the possibility that the immunity of T-even phages to mutation by methyl methanesulphonate (MMS) was due to the unreactivity of OHMeCyt towards this agent. Both cytosine and OHMeCyt reacted equally well with the methylating agents MMS and N-methyl-N-nitrosourea (MNU) affording 6% and less than 1% respectively of the 3-substituted derivative. No product was isolated following subjection of the bases to reaction with ethyl methane-sulphonate (EMS), N-ethyl-N-nitrosourea (ENU) or iso-propyl methane-sulphonate (iPMS)."}
{"id": "PMID:193651", "title": "Comparison of the photochemical and enzymic generation of excited states of oxygen on the induction of benzo(alpha)pyrene mono-oxygenase in liver cell cultures.", "content": "The photochemical generation of excited states of oxygen such as the superoxide ion(O-2) and singlet oxygen (1o2) by the mild illumination of culture medium containing riboflavin induces benzo(alpha)pyrene mono-oxygenase in 3 different cell lines derived from rat liver. Similar rates of O-2 generation can be produced by the action of xanthine oxidase on xanthine yet this system does not induce the mono-oxygenase. This result confirms that the mono-oxygenase induction is not mediated by O-2 is not mediated by O-2 and that 1O2 is the most likely candidate for stimulating the mono-oxygenase activity.", "contents": "Comparison of the photochemical and enzymic generation of excited states of oxygen on the induction of benzo(alpha)pyrene mono-oxygenase in liver cell cultures. The photochemical generation of excited states of oxygen such as the superoxide ion(O-2) and singlet oxygen (1o2) by the mild illumination of culture medium containing riboflavin induces benzo(alpha)pyrene mono-oxygenase in 3 different cell lines derived from rat liver. Similar rates of O-2 generation can be produced by the action of xanthine oxidase on xanthine yet this system does not induce the mono-oxygenase. This result confirms that the mono-oxygenase induction is not mediated by O-2 is not mediated by O-2 and that 1O2 is the most likely candidate for stimulating the mono-oxygenase activity."}
{"id": "PMID:193653", "title": "[Demonstration of specific receptors for angiotensin III in rat adrenal glands].", "content": "Distinct and specific binding sites for 3H-angiotensin II (A II) AND 3H-angiotensin III (A III) have been demonstrated in Rat adrenal gland preparations. A III binding sites have the highest affinity (KD29C1-2.10(-10)M) for the 2-8 heptapeptide. This suggests the possibility of a separate and distinct physiological role for the 2-8 heptapeptide, mediated via such A III binding sites.", "contents": "[Demonstration of specific receptors for angiotensin III in rat adrenal glands]. Distinct and specific binding sites for 3H-angiotensin II (A II) AND 3H-angiotensin III (A III) have been demonstrated in Rat adrenal gland preparations. A III binding sites have the highest affinity (KD29C1-2.10(-10)M) for the 2-8 heptapeptide. This suggests the possibility of a separate and distinct physiological role for the 2-8 heptapeptide, mediated via such A III binding sites."}
{"id": "PMID:193654", "title": "[Stimulation by ACTH of protein synthesis in cultured adrenal cells. Absence of an effect by cyclin AMP].", "content": "ACTH stimulates the incorporation of 14C-leucine into proteins of adrenal tumor cells in culture. This stimulation though about 20% over controls is statistically significant. Cyclic AMP did not reproduce the stimulation observed with ACTH.", "contents": "[Stimulation by ACTH of protein synthesis in cultured adrenal cells. Absence of an effect by cyclin AMP]. ACTH stimulates the incorporation of 14C-leucine into proteins of adrenal tumor cells in culture. This stimulation though about 20% over controls is statistically significant. Cyclic AMP did not reproduce the stimulation observed with ACTH."}
{"id": "PMID:193655", "title": "Regulation of norepinephrine release from cardiac sympathetic fibers in the dog by presynaptic alpha- and beta-receptors.", "content": "The effect of phenoxybenzamine (PBA), desmethylimipramine (DMI), clonidine (CLND), sotalol (STL), and isoproterenol (ISPR) on the release of endogenous norepinephrine (NE) from the heart on right cardioaccelerator nerve stimulation was studied in anesthetized dogs. Under control conditions, the catecholamine levels in coronary sinus blood increased linearly with increasing frequencies of stimulation up to 10 Hz and did not increase further at 30 Hz. The release of NE was markedly enhanced after PBA (1 mg/kg, iv) and DMI (1 mg/kg, iv). The enhanced release of NE after DMI, but not after PBA, was associated with a prolonged response in heart rate. In contrast, NE release was reduced after CLND (15 microgram/kg, iv) at stimulation frequencies of 1 and 2 Hz and this was associated with reduced responses in heart rate and left ventricular dtp/dt. STL (5 mg/kg, iv) reduced significantly the release of NE at stimulation frequencies of 1-5 Hz, whereas ISPR enhanced NE outflow at frequencies of 1-4 Hz. These results support the existence of both negative and positive feedback mechanisms on the release of norepinephrine by cardiac sympathetic fibers mediated through presynaptic alpha- and beta-adrenoreceptors, respectively. The functional significance of these mechanisms is also suggested by the correlation found between changes in NE release and variations in cardiac responses under the various drug treatements.", "contents": "Regulation of norepinephrine release from cardiac sympathetic fibers in the dog by presynaptic alpha- and beta-receptors. The effect of phenoxybenzamine (PBA), desmethylimipramine (DMI), clonidine (CLND), sotalol (STL), and isoproterenol (ISPR) on the release of endogenous norepinephrine (NE) from the heart on right cardioaccelerator nerve stimulation was studied in anesthetized dogs. Under control conditions, the catecholamine levels in coronary sinus blood increased linearly with increasing frequencies of stimulation up to 10 Hz and did not increase further at 30 Hz. The release of NE was markedly enhanced after PBA (1 mg/kg, iv) and DMI (1 mg/kg, iv). The enhanced release of NE after DMI, but not after PBA, was associated with a prolonged response in heart rate. In contrast, NE release was reduced after CLND (15 microgram/kg, iv) at stimulation frequencies of 1 and 2 Hz and this was associated with reduced responses in heart rate and left ventricular dtp/dt. STL (5 mg/kg, iv) reduced significantly the release of NE at stimulation frequencies of 1-5 Hz, whereas ISPR enhanced NE outflow at frequencies of 1-4 Hz. These results support the existence of both negative and positive feedback mechanisms on the release of norepinephrine by cardiac sympathetic fibers mediated through presynaptic alpha- and beta-adrenoreceptors, respectively. The functional significance of these mechanisms is also suggested by the correlation found between changes in NE release and variations in cardiac responses under the various drug treatements."}
{"id": "PMID:193656", "title": "Concentration and composition of the lipoprotein classes in human umbilical cord serum.", "content": "The concentration and composition of the lipoprotein density classes d less than 1.006 (VLDL), d = 1.006 - 1.064 (LDL), and d = 1.064 - 1.21 (HDL) of human umbilical cord serum were investigated by means of preparative ultracentrifugation. The concentrations of all the density classes, in particular that of the VLDL, are lower than in adults; the values correspond to 8.1 (VLDL), 59.2 (LDL), and 77.4 (HDL) mg/100 ml. About 15% of the total cholesterol and roughly 40% of the total lipid phosphorus did not float at the highest density of 1.21. The composition of the LDL and the HDL was principally in agreement with the pattern obtained in adults. The VLDL of the cord serum, however, showed a lower amount of triglycerides (45%) and a higher content of proteins (22%) than the VLDL from serum of adults. In cord serum only 25% of the total triglycerides are associated with the VLDL fraction, while more than 50% of the triglycerides circulate as a constituent of the LDL.", "contents": "Concentration and composition of the lipoprotein classes in human umbilical cord serum. The concentration and composition of the lipoprotein density classes d less than 1.006 (VLDL), d = 1.006 - 1.064 (LDL), and d = 1.064 - 1.21 (HDL) of human umbilical cord serum were investigated by means of preparative ultracentrifugation. The concentrations of all the density classes, in particular that of the VLDL, are lower than in adults; the values correspond to 8.1 (VLDL), 59.2 (LDL), and 77.4 (HDL) mg/100 ml. About 15% of the total cholesterol and roughly 40% of the total lipid phosphorus did not float at the highest density of 1.21. The composition of the LDL and the HDL was principally in agreement with the pattern obtained in adults. The VLDL of the cord serum, however, showed a lower amount of triglycerides (45%) and a higher content of proteins (22%) than the VLDL from serum of adults. In cord serum only 25% of the total triglycerides are associated with the VLDL fraction, while more than 50% of the triglycerides circulate as a constituent of the LDL."}
{"id": "PMID:193657", "title": "Plasma triglyceride secretion and metabolism in chronic renal failure.", "content": "Endogenous very low density lipoprotein triglyceride (VLDL-TG) production rate has been studied in 13 patients with chronic renal failure who were not on dialysis treatment. In these patients the VLDL-TG plasma concentration was significanlty raised when compared with the control group; the fractional turnover rate was reduced but the absolute turnover rate was increased. The results suggest that increased hepatic production of VLDL-TG is a contributory factor to the hypertriglyceridaemia of chronic renal failure.", "contents": "Plasma triglyceride secretion and metabolism in chronic renal failure. Endogenous very low density lipoprotein triglyceride (VLDL-TG) production rate has been studied in 13 patients with chronic renal failure who were not on dialysis treatment. In these patients the VLDL-TG plasma concentration was significanlty raised when compared with the control group; the fractional turnover rate was reduced but the absolute turnover rate was increased. The results suggest that increased hepatic production of VLDL-TG is a contributory factor to the hypertriglyceridaemia of chronic renal failure."}
{"id": "PMID:193658", "title": "The combined effect of growth hormone and methandrostenolone on the linear growth of patients with multiple pituitary hormone deficiencies.", "content": "Six patients with multiple pituitary hormone deficiencies (MPHD) were initially treated with separate courses of methandrostenolone and growth hormone and later with the two drugs combined. During the basal period the mean growth velocity was 2.8 cm/year. Methandrostenolone alone, 0.02-0.05 mg/kg/day given to four of the patients led to an acceleration of the growth velocity to a mean of 5.0 cm/year, while growth hormone 6 mg/week alone accelerated the growth rate to a mean of 6.0 cm/year. Combined therapy led to a striking increase in the mean growth rate to 9.3 cm/year. The shortcoming of the combined growth hormone-androgen therapy was the fast acceleration in skeletal maturation even after short-term administration.", "contents": "The combined effect of growth hormone and methandrostenolone on the linear growth of patients with multiple pituitary hormone deficiencies. Six patients with multiple pituitary hormone deficiencies (MPHD) were initially treated with separate courses of methandrostenolone and growth hormone and later with the two drugs combined. During the basal period the mean growth velocity was 2.8 cm/year. Methandrostenolone alone, 0.02-0.05 mg/kg/day given to four of the patients led to an acceleration of the growth velocity to a mean of 5.0 cm/year, while growth hormone 6 mg/week alone accelerated the growth rate to a mean of 6.0 cm/year. Combined therapy led to a striking increase in the mean growth rate to 9.3 cm/year. The shortcoming of the combined growth hormone-androgen therapy was the fast acceleration in skeletal maturation even after short-term administration."}
{"id": "PMID:193659", "title": "Evaluation of 3 hour metyrapone test in children and adolescents.", "content": "An evaluation of a new 3 h metyrapone test is presented. The test consists of one oral dose of metyrapone given at 08.00-09.00 hours, and determination of plasma deoxycortisol from a single capillary blood sample taken 3 h later. The test has been assessed in children and adolescents in conjunction with a 5 day metyrapone test, insulin test, vasopressin test, and ACTH test in forty-five reference subjects, in thirty-six hypopituitary subjects with normal or deficient ACTH secretion, in three subjects with primary adrenocortical disease and in ten subjects prior to and after pharmacological prednisone medication. During the first hour after metyrapone the plasma cortisol level decreased to almost the low level maintained for the rest of the 3 h period. The plasma deoxycortisol concentration was basally less than or equal to 35 nmol/l and increased continuously during the 3 h period to the mean level of 299 (95% confidence interval 133-669) nmol/l in the reference subjects. The new test proved to be as accurate as the insulin test in detecting ACTH deficiency. No significant rise was observed in the plasma somatotrophin (GH) level in those children who had a normal GH response to insulin hypoglycaemia.", "contents": "Evaluation of 3 hour metyrapone test in children and adolescents. An evaluation of a new 3 h metyrapone test is presented. The test consists of one oral dose of metyrapone given at 08.00-09.00 hours, and determination of plasma deoxycortisol from a single capillary blood sample taken 3 h later. The test has been assessed in children and adolescents in conjunction with a 5 day metyrapone test, insulin test, vasopressin test, and ACTH test in forty-five reference subjects, in thirty-six hypopituitary subjects with normal or deficient ACTH secretion, in three subjects with primary adrenocortical disease and in ten subjects prior to and after pharmacological prednisone medication. During the first hour after metyrapone the plasma cortisol level decreased to almost the low level maintained for the rest of the 3 h period. The plasma deoxycortisol concentration was basally less than or equal to 35 nmol/l and increased continuously during the 3 h period to the mean level of 299 (95% confidence interval 133-669) nmol/l in the reference subjects. The new test proved to be as accurate as the insulin test in detecting ACTH deficiency. No significant rise was observed in the plasma somatotrophin (GH) level in those children who had a normal GH response to insulin hypoglycaemia."}
{"id": "PMID:193661", "title": "Human polymorphonuclear leucocytes as mediators of antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells.", "content": "Human polymorphonuclear leucocytes (PML) were able to mediate antibody-dependent cellular cytotoxicity (ADCC) against target cells acutely infected with type 1 Herpes simplex virus. The reaction mediated by PML occurred more slowly and required higher concentrations of immune serum than that mediated by human mononuclear cells (MC). At the same ratio of effector cells to target cells, PML-mediated ADCC was less than MC-mediated ADCC. The observed relationship between the number of effector cells added, and the number of target cells lysed, showed that cytolysis mediated by both PML and MC was consistent with 'one hit' probability predictions. This suggested that target cell death resulted from an interaction with a single effector cell. The calculated frequency of effector cells in PML preparation was similar to that in MC, approximately 3-5%. Preliminary examination of the nature of the effector cells suggested that they did not comprise a morphologically distinct subclass of PML. These experiments demonstrate a possible new role for PML in host defence against viral infections.", "contents": "Human polymorphonuclear leucocytes as mediators of antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells. Human polymorphonuclear leucocytes (PML) were able to mediate antibody-dependent cellular cytotoxicity (ADCC) against target cells acutely infected with type 1 Herpes simplex virus. The reaction mediated by PML occurred more slowly and required higher concentrations of immune serum than that mediated by human mononuclear cells (MC). At the same ratio of effector cells to target cells, PML-mediated ADCC was less than MC-mediated ADCC. The observed relationship between the number of effector cells added, and the number of target cells lysed, showed that cytolysis mediated by both PML and MC was consistent with 'one hit' probability predictions. This suggested that target cell death resulted from an interaction with a single effector cell. The calculated frequency of effector cells in PML preparation was similar to that in MC, approximately 3-5%. Preliminary examination of the nature of the effector cells suggested that they did not comprise a morphologically distinct subclass of PML. These experiments demonstrate a possible new role for PML in host defence against viral infections."}
{"id": "PMID:193662", "title": "Smooth muscle antibody in Burkitt's lymphoma and in nasopharyngeal carcinoma.", "content": "Smooth muscle antibodies (SMA) with specificity for actin, were found with a higher frequency in sera from Burkitt's lymphoma (BL) and nasopharyngeal carcinoma (NPC) patients than in sera from matched controls. No correlation could be found between SMA and anti-Epstein-Barr virus (EBV) antibody titres. There was no parallelism, in individual sera, between the finding of SMA and the occurrence of cold lymphocytotoxins, aother antibody activity found with an abnormally high frequency among BL and NPC patients. The reason why actin, a weak antigen in experimental animals, may become immunogenic in humans remains unexplained.", "contents": "Smooth muscle antibody in Burkitt's lymphoma and in nasopharyngeal carcinoma. Smooth muscle antibodies (SMA) with specificity for actin, were found with a higher frequency in sera from Burkitt's lymphoma (BL) and nasopharyngeal carcinoma (NPC) patients than in sera from matched controls. No correlation could be found between SMA and anti-Epstein-Barr virus (EBV) antibody titres. There was no parallelism, in individual sera, between the finding of SMA and the occurrence of cold lymphocytotoxins, aother antibody activity found with an abnormally high frequency among BL and NPC patients. The reason why actin, a weak antigen in experimental animals, may become immunogenic in humans remains unexplained."}
{"id": "PMID:193663", "title": "Inhibition of the in vitro outgrowth of Epstein-Barr virus-transformed lymphocytes by thymus-dependent lymphocytes from infectious mononucleosis patients.", "content": "Known numbers of thymus-dependent (T) lymphocytes, obtained by positive selection from the blood of acute infectious mononucleosis (IM) patients and from control donors, were added to target cultures of foetal mononuclear cells within 0-7 days of exposure of the target cells to one of a range of doses of Epstein-Barr (EB) virus. The subsequent outgrowth of virus-transformed foetal cells was markedly inhibited by the presence in the cultures of IM-derived T cells, whilst similar numbers of T cells prepared either from cord blood or from adult donors seronegative for EB virus had little or no inhibitory effect. Target foetal cells treated with papain to remove any viral envelope material remaining on the cell surface after infection, were just as sensitive as untreated cells to the addition of IM-derived T cells. It is concluded that the inhibition cannot be mediated through recognition either of viral envelope structures on the surface of infected cells or of the antigenically related virus-determined membrane antigen, MA, but must depend upon recognition of the lymphocyte-detected membrane antigen, LYDMA. The regularity with which IM-derived T cells block the outgrowth of virus-transformed foetal cells suggests that LYDMA consistently appears on the surface of infected foetal cells before the establishment of transformed foci, but is unlikely to be directly associated with the cells' existing histocompatibility antigens.", "contents": "Inhibition of the in vitro outgrowth of Epstein-Barr virus-transformed lymphocytes by thymus-dependent lymphocytes from infectious mononucleosis patients. Known numbers of thymus-dependent (T) lymphocytes, obtained by positive selection from the blood of acute infectious mononucleosis (IM) patients and from control donors, were added to target cultures of foetal mononuclear cells within 0-7 days of exposure of the target cells to one of a range of doses of Epstein-Barr (EB) virus. The subsequent outgrowth of virus-transformed foetal cells was markedly inhibited by the presence in the cultures of IM-derived T cells, whilst similar numbers of T cells prepared either from cord blood or from adult donors seronegative for EB virus had little or no inhibitory effect. Target foetal cells treated with papain to remove any viral envelope material remaining on the cell surface after infection, were just as sensitive as untreated cells to the addition of IM-derived T cells. It is concluded that the inhibition cannot be mediated through recognition either of viral envelope structures on the surface of infected cells or of the antigenically related virus-determined membrane antigen, MA, but must depend upon recognition of the lymphocyte-detected membrane antigen, LYDMA. The regularity with which IM-derived T cells block the outgrowth of virus-transformed foetal cells suggests that LYDMA consistently appears on the surface of infected foetal cells before the establishment of transformed foci, but is unlikely to be directly associated with the cells' existing histocompatibility antigens."}
{"id": "PMID:193666", "title": "Non-stedy-state studies of low-density-liproprotein turnover in familial hypercholesterolaemia.", "content": "1. The non-steady-state turnover of low-density lipoprotein (LDL), labelled in its apoprotein moiety (apo-B) with 131I, was determined in four patients with familial hypercholesterolaemia, three of them homozygotes. 2. The fractional and absolute catabolic rates (FCR and ACR) of LDL-apo-B were determined by relating the excretion of radioactivity, measured in urine in vitro and by whole-body counter in vivo, to plasma radioactivity and to LDL specific radioactivity respectively. 3. The FCR remained relatively constant, even after marked reduction of LDL pool size by means of plasma exchange. This confirms the existence of an intrinsic defect in LDL catabolism in familial hypercholesterolaemia. 4. LDL-apo-B synthesis, determined by summing the ACR and the daily increment in plasma LDL, was much higher in the three homozygotes than in the one heterozygote, in whom the synthetic rate was normal. 5. These results illustrate the usefulness of combining plasma exchange and whole-body radioactivy counting as a means of examining the relationship between the turnover and pool size of a 131I-labelled protein, such as LDL.", "contents": "Non-stedy-state studies of low-density-liproprotein turnover in familial hypercholesterolaemia. 1. The non-steady-state turnover of low-density lipoprotein (LDL), labelled in its apoprotein moiety (apo-B) with 131I, was determined in four patients with familial hypercholesterolaemia, three of them homozygotes. 2. The fractional and absolute catabolic rates (FCR and ACR) of LDL-apo-B were determined by relating the excretion of radioactivity, measured in urine in vitro and by whole-body counter in vivo, to plasma radioactivity and to LDL specific radioactivity respectively. 3. The FCR remained relatively constant, even after marked reduction of LDL pool size by means of plasma exchange. This confirms the existence of an intrinsic defect in LDL catabolism in familial hypercholesterolaemia. 4. LDL-apo-B synthesis, determined by summing the ACR and the daily increment in plasma LDL, was much higher in the three homozygotes than in the one heterozygote, in whom the synthetic rate was normal. 5. These results illustrate the usefulness of combining plasma exchange and whole-body radioactivy counting as a means of examining the relationship between the turnover and pool size of a 131I-labelled protein, such as LDL."}
{"id": "PMID:193669", "title": "Variations in the number of uterine angiotensin receptors following changes in plasma angiotensin levels.", "content": "3H-labelled angiotensin II binding to receptor sites was studied in plasma membranes isolated from myometrial homogenates of uterine horns. Removal of the kidneys, which results in the disappearance of plasma angiotensin II, was followed by an increase in the number of uterine receptor sites without significant variation in the apparent dissociation constant, which became significant 15 h after nephrectomy. Acute pressor intravenous injection of angiotensin II into nephrectomized rats immediately before removing uteri, did not affect the number of uterine angiotensin receptors, whereas long-lasting angiotensin infusion did reduce the number of receptors. These results provided an explanation for the specific supersensitivity to angiotensin II, observed in uteri excised from nephrectomized rats, which cannot be accounted for by variations in the occupancy of receptor sites. These results also demonstrate that the number of angiotensin receptors, at least in uterine contractile cells, is affected by chronic variations of endogenous angiotensin levels.", "contents": "Variations in the number of uterine angiotensin receptors following changes in plasma angiotensin levels. 3H-labelled angiotensin II binding to receptor sites was studied in plasma membranes isolated from myometrial homogenates of uterine horns. Removal of the kidneys, which results in the disappearance of plasma angiotensin II, was followed by an increase in the number of uterine receptor sites without significant variation in the apparent dissociation constant, which became significant 15 h after nephrectomy. Acute pressor intravenous injection of angiotensin II into nephrectomized rats immediately before removing uteri, did not affect the number of uterine angiotensin receptors, whereas long-lasting angiotensin infusion did reduce the number of receptors. These results provided an explanation for the specific supersensitivity to angiotensin II, observed in uteri excised from nephrectomized rats, which cannot be accounted for by variations in the occupancy of receptor sites. These results also demonstrate that the number of angiotensin receptors, at least in uterine contractile cells, is affected by chronic variations of endogenous angiotensin levels."}
{"id": "PMID:193672", "title": "Nuclear envelope inclusions demonstrated by freeze-fracture.", "content": "Inclusions in the perinuclear space of the nuclear envelope of human diploid (MRC-5) fibroblasts, limpet (Patella vulgata) haemocytes, and yeast (Saccharomyces cerevisiae) as observed with the freeze-fracture technique are described. The significance of these inclusions is discussed and it is tentatively concluded that they represent vesicles engaged in transporting macromolecules between nucleus and cytoplasm. Although the inclusions were infrequently observed, their demonstration in mammalian, invertebrate and lower eukaryotic cell types raises the possibility that this form of nucleocytoplasmic exchange may potentially be adopted under appropriate circumstances by the eukaryotic cell in general.", "contents": "Nuclear envelope inclusions demonstrated by freeze-fracture. Inclusions in the perinuclear space of the nuclear envelope of human diploid (MRC-5) fibroblasts, limpet (Patella vulgata) haemocytes, and yeast (Saccharomyces cerevisiae) as observed with the freeze-fracture technique are described. The significance of these inclusions is discussed and it is tentatively concluded that they represent vesicles engaged in transporting macromolecules between nucleus and cytoplasm. Although the inclusions were infrequently observed, their demonstration in mammalian, invertebrate and lower eukaryotic cell types raises the possibility that this form of nucleocytoplasmic exchange may potentially be adopted under appropriate circumstances by the eukaryotic cell in general."}
{"id": "PMID:193673", "title": "[Criteria for surgical therapy of hypothalamo-hypophyseal Cushing's syndrome].", "content": "This article tries to give criteria for the two possible modes of treatment of the pituitary-dependent Cushing's syndrome. Patients (n = 6) who show no secondary complications on Cushing's disease should undergo implantation of 90Y and/or 192Ir into the pituitary gland. After implantation, the excessive secretion of ACTH is suppressed to normal values. The symptoms of Cushing's syndrome disappear. Following the operation, certain patients must also receive hormonal replacement therapy. Fertility is not always preserved. Total adrenalectomy as the alternative procedure is performed in adults with advanced symptoms of the disease (n = 3) and in children (n = 3). Following removal of the adrenal glands, the symptoms of Cushing's syndrome disappear. The appearance of Nelson's tumor after adrenalectomy (10% in the literature) is discussed.", "contents": "[Criteria for surgical therapy of hypothalamo-hypophyseal Cushing's syndrome]. This article tries to give criteria for the two possible modes of treatment of the pituitary-dependent Cushing's syndrome. Patients (n = 6) who show no secondary complications on Cushing's disease should undergo implantation of 90Y and/or 192Ir into the pituitary gland. After implantation, the excessive secretion of ACTH is suppressed to normal values. The symptoms of Cushing's syndrome disappear. Following the operation, certain patients must also receive hormonal replacement therapy. Fertility is not always preserved. Total adrenalectomy as the alternative procedure is performed in adults with advanced symptoms of the disease (n = 3) and in children (n = 3). Following removal of the adrenal glands, the symptoms of Cushing's syndrome disappear. The appearance of Nelson's tumor after adrenalectomy (10% in the literature) is discussed."}
{"id": "PMID:193675", "title": "Lacrimal flow.", "content": "Syncinetic reflex or isolated orbicularis muscle contraction squeezes the tearsac between Horner's muscle and the inner palpebral ligament, closes the canaliculi and prevents conjunctival fornix backflow, while the tears are expressed (pseudo-peristaltism) towards the nose through the flexible naso-lacrimal canal. The diameter at the level of the canaliculi should be kept optimal in order to allow proper suction towards the tearsac and free capillarity since surface tension varies to a lesser extent. Scopy of contrast lacrimal outflow-channels provides important information on the morphology and the physiopathology of the lacrimal ducts, ruling out eventual functional origin of the lacrimation. The technique is especially important in decision making for treatment (allergic conditions, congenital dacryocystitis) for evaluation of dacryocystorhinostomy, for the early diagnosis and management of infection, inflammation and posttraumatic conditions of the face and anterior skull.", "contents": "Lacrimal flow. Syncinetic reflex or isolated orbicularis muscle contraction squeezes the tearsac between Horner's muscle and the inner palpebral ligament, closes the canaliculi and prevents conjunctival fornix backflow, while the tears are expressed (pseudo-peristaltism) towards the nose through the flexible naso-lacrimal canal. The diameter at the level of the canaliculi should be kept optimal in order to allow proper suction towards the tearsac and free capillarity since surface tension varies to a lesser extent. Scopy of contrast lacrimal outflow-channels provides important information on the morphology and the physiopathology of the lacrimal ducts, ruling out eventual functional origin of the lacrimation. The technique is especially important in decision making for treatment (allergic conditions, congenital dacryocystitis) for evaluation of dacryocystorhinostomy, for the early diagnosis and management of infection, inflammation and posttraumatic conditions of the face and anterior skull."}
{"id": "PMID:193676", "title": "[Herpes simplex causing a therapy-resistant panaritium (author's transl)].", "content": "In an eight-month-old child an inflammation developed in the region of the nail bed of the right middle finger. It showed no improvement after immobilisation, extraction of the nail and antibiotics. After ten months unsuccessful treatment electron microscopy of the inflammatory tissue showed numerous Herpes simplex viruses. These increased rapidly in tissue culture and could be neutralised with antibodies against Herpes simplex virus.", "contents": "[Herpes simplex causing a therapy-resistant panaritium (author's transl)]. In an eight-month-old child an inflammation developed in the region of the nail bed of the right middle finger. It showed no improvement after immobilisation, extraction of the nail and antibiotics. After ten months unsuccessful treatment electron microscopy of the inflammatory tissue showed numerous Herpes simplex viruses. These increased rapidly in tissue culture and could be neutralised with antibodies against Herpes simplex virus."}
{"id": "PMID:193674", "title": "Extragenital mixed heterologous tumor of M\u00fcllerian type arising in the cecal peritoneum: report of a case.", "content": "A mixed heterologous tumor of m\u00fcllerian type arising in the cecal serosa of an elderly woman is reported. There was no history of endometriosis, and no evidence of the latter was found in the surgical specimen or at autopsy. Evidence of mesothelial origin was found microscopically in the adjacent cecal peritoneum. A review of medical literature on mixed heterologous tumors of m\u00fcllerian type reveals that heretofore they have originated only in the genital system.", "contents": "Extragenital mixed heterologous tumor of M\u00fcllerian type arising in the cecal peritoneum: report of a case. A mixed heterologous tumor of m\u00fcllerian type arising in the cecal serosa of an elderly woman is reported. There was no history of endometriosis, and no evidence of the latter was found in the surgical specimen or at autopsy. Evidence of mesothelial origin was found microscopically in the adjacent cecal peritoneum. A review of medical literature on mixed heterologous tumors of m\u00fcllerian type reveals that heretofore they have originated only in the genital system."}
{"id": "PMID:193678", "title": "[EEG in neuropediatrics (author's transl)].", "content": "After remarks about the history of pediatric electroencephalography some particularly important neurophysiological and especially electroencephalographical studies out-of the last ten years are reviewed: polygraphic studies in healthy and sick newborns, spectralanalytical investigations of the EEG in twins, infants and older children. The review is closed by some critical considerations about possibilities and limitations of the automatic analysis of the childhood EEG.", "contents": "[EEG in neuropediatrics (author's transl)]. After remarks about the history of pediatric electroencephalography some particularly important neurophysiological and especially electroencephalographical studies out-of the last ten years are reviewed: polygraphic studies in healthy and sick newborns, spectralanalytical investigations of the EEG in twins, infants and older children. The review is closed by some critical considerations about possibilities and limitations of the automatic analysis of the childhood EEG."}
{"id": "PMID:193681", "title": "Inhibition of thyrotropin- and dibutyryl cyclic AMP-induced secretion of thyroxine and triiodothyronine by catecholamines.", "content": "Thyrotropin (TSH), 1 MU/ml and N6, O2'-dibutyryl adenosine 3',5-cyclic monophosphoric acid (dbcAMP) greatly enhanced the release of thyroxine (T4) and triiodothyronine (T3) from mouse thyroids incubated in vitro. L-Epinephrine (E) and L-norepinephrine (NE) strongly inhibited the TSH and dbcAMP-stimulated release of thyroid hormones; L-isoproterenol (IPNE) exerted a relatively weak inhibition. The inhibition by catecholamines was prevented by the alpha-adrenergic blocker, phentolamine; L-propranolol, a beta-adrenergic blocker, had no effect on the inhibition. The TSH-induced release of thyroid hormones was not affected by adrenergic blockers. Epinephrine did not affect the increase in thyroidal cAMP content induced by TSH. These results indicate that catecholamines act by way of an alpha-adrenergic receptor to suppress TSH-stimulated release of thyroid hormones at a point beyond cAMP formation.", "contents": "Inhibition of thyrotropin- and dibutyryl cyclic AMP-induced secretion of thyroxine and triiodothyronine by catecholamines. Thyrotropin (TSH), 1 MU/ml and N6, O2'-dibutyryl adenosine 3',5-cyclic monophosphoric acid (dbcAMP) greatly enhanced the release of thyroxine (T4) and triiodothyronine (T3) from mouse thyroids incubated in vitro. L-Epinephrine (E) and L-norepinephrine (NE) strongly inhibited the TSH and dbcAMP-stimulated release of thyroid hormones; L-isoproterenol (IPNE) exerted a relatively weak inhibition. The inhibition by catecholamines was prevented by the alpha-adrenergic blocker, phentolamine; L-propranolol, a beta-adrenergic blocker, had no effect on the inhibition. The TSH-induced release of thyroid hormones was not affected by adrenergic blockers. Epinephrine did not affect the increase in thyroidal cAMP content induced by TSH. These results indicate that catecholamines act by way of an alpha-adrenergic receptor to suppress TSH-stimulated release of thyroid hormones at a point beyond cAMP formation."}
{"id": "PMID:193682", "title": "Site of action of growth hormone on adrenocortical steroidogenesis in rats.", "content": "Studies were carried out to define the mechanism of action of growth hormone on adrenocortical steroidogenesis in hypophysectomized female rats. ACTH administration for 7 days increased corticosterone secretion in vivo and corticosterone production by adrenal tissue in vitro. Adrenal mitochondrial and microsomal cytochrome P-450 concentrations as well as the activities of cytochrome P-450-dependent enzymes (cholesterol sidechain cleavage, 11beta-hydroxylase, 21-hydroxylase) were also increased by ACTH. Administration of bovine growth hormone alone to hypophysectomized rats had no effect on any of the parameters evaluated. However, when given in combination with ACTH, growth hormone synergistically enhanced the effects of ACTH on cholesterol sidechain cleavage activity and corticosterone secretion. The magnitude of the pregnenolone-induced difference spectrum in adrenal mitochondria, indicative of cholesterol binding to cytochrome P-450, was also increased by growth hormone, but neither cytochrome P-450 content nor the activities of other steroidogenic enzymes were affected. The results indicate that growth hormone interacts with ACTH to promote corticosterone secretion by increasing the association of cholesterol with adrenal mitochondrial cytochrome P-450, thereby increasing the activity of cholesterol sidechain cleavage, the rate-limiting step in steroidogenesis.", "contents": "Site of action of growth hormone on adrenocortical steroidogenesis in rats. Studies were carried out to define the mechanism of action of growth hormone on adrenocortical steroidogenesis in hypophysectomized female rats. ACTH administration for 7 days increased corticosterone secretion in vivo and corticosterone production by adrenal tissue in vitro. Adrenal mitochondrial and microsomal cytochrome P-450 concentrations as well as the activities of cytochrome P-450-dependent enzymes (cholesterol sidechain cleavage, 11beta-hydroxylase, 21-hydroxylase) were also increased by ACTH. Administration of bovine growth hormone alone to hypophysectomized rats had no effect on any of the parameters evaluated. However, when given in combination with ACTH, growth hormone synergistically enhanced the effects of ACTH on cholesterol sidechain cleavage activity and corticosterone secretion. The magnitude of the pregnenolone-induced difference spectrum in adrenal mitochondria, indicative of cholesterol binding to cytochrome P-450, was also increased by growth hormone, but neither cytochrome P-450 content nor the activities of other steroidogenic enzymes were affected. The results indicate that growth hormone interacts with ACTH to promote corticosterone secretion by increasing the association of cholesterol with adrenal mitochondrial cytochrome P-450, thereby increasing the activity of cholesterol sidechain cleavage, the rate-limiting step in steroidogenesis."}
{"id": "PMID:193685", "title": "Thyrotropin binding and long acting thyroid stimulator absorbing activities in subcellular fractions from isolated thyroid cells and thyroid homogenates.", "content": "The ability of various thyroid subcellular fractions to bind [125I]iodo TSH and to absorb long-acting thyroid stimulator (LATS) and thyroid stimulating immunoglobulins (TSI) activities was examined. Membranes purified from thyroid homogenates or isolated thyroid cells absorbed LATS/TSI activities and specifically bound [125I]iodo TSH. Purified thyroglobulin, nuclei, mitochondria and ribosomes did not bind [125I]iodo TSH nor did they absorb LATS/TSI activities. Cell sap obtained by gentle lysis of isolated thyroid cells failed to absorb LATS/TSI activities and to bind labeled hormone. However, freeze-thawing of the cells fragmented the membranes, releasing [125I]iodo TSH binding as well as LATS/TSI absorbing activities into the soluble (cell sap) fraction. The results suggest that the LATS/TSI antigen is of cell surface origin, includes the TSH receptor or larger membrane fragments containing the receptor, and that its release into the soluble fraction is due to the fragmentation of the thyroid membrane during homogenization and preparative procedures.", "contents": "Thyrotropin binding and long acting thyroid stimulator absorbing activities in subcellular fractions from isolated thyroid cells and thyroid homogenates. The ability of various thyroid subcellular fractions to bind [125I]iodo TSH and to absorb long-acting thyroid stimulator (LATS) and thyroid stimulating immunoglobulins (TSI) activities was examined. Membranes purified from thyroid homogenates or isolated thyroid cells absorbed LATS/TSI activities and specifically bound [125I]iodo TSH. Purified thyroglobulin, nuclei, mitochondria and ribosomes did not bind [125I]iodo TSH nor did they absorb LATS/TSI activities. Cell sap obtained by gentle lysis of isolated thyroid cells failed to absorb LATS/TSI activities and to bind labeled hormone. However, freeze-thawing of the cells fragmented the membranes, releasing [125I]iodo TSH binding as well as LATS/TSI absorbing activities into the soluble (cell sap) fraction. The results suggest that the LATS/TSI antigen is of cell surface origin, includes the TSH receptor or larger membrane fragments containing the receptor, and that its release into the soluble fraction is due to the fragmentation of the thyroid membrane during homogenization and preparative procedures."}
{"id": "PMID:193686", "title": "Effects of prostaglandin E1 and indomethacin on ACTH, prolactin, GH and LH from rat pituitary in vitro.", "content": "The effects of prostaglandin E1 (PGE1) and indomethacin (IDM) on the release of several pituitary hormones from the rat pituitary were investigated in vitro. An addition of 2 microng/ml of PGE1 to the medium elicited the release of growth hormone (GH) and prolactin, but not of adrenocorticotropin (ACTH) and luteinizing hormone (LH). Although the addition of 1 microng/ml of IDM alone resulted in no effect on the basal release of these hormones, IDM diminished the release of ACTH induced by crude rat hypothalamic extracts (HE) or lysine-8-vasopressin (LVP), and LH induced by HE or luteinizing hormone-releasing hormone (LH-RH). These findings implicate that a part of PGE1 action might be a direct one on the pituitary gland and PGE1 might release GH and prolactin, whereas IDM might have a direct action on the pituitary gland, and that blunt the release of these pituitary hormones induced by several stimuli.", "contents": "Effects of prostaglandin E1 and indomethacin on ACTH, prolactin, GH and LH from rat pituitary in vitro. The effects of prostaglandin E1 (PGE1) and indomethacin (IDM) on the release of several pituitary hormones from the rat pituitary were investigated in vitro. An addition of 2 microng/ml of PGE1 to the medium elicited the release of growth hormone (GH) and prolactin, but not of adrenocorticotropin (ACTH) and luteinizing hormone (LH). Although the addition of 1 microng/ml of IDM alone resulted in no effect on the basal release of these hormones, IDM diminished the release of ACTH induced by crude rat hypothalamic extracts (HE) or lysine-8-vasopressin (LVP), and LH induced by HE or luteinizing hormone-releasing hormone (LH-RH). These findings implicate that a part of PGE1 action might be a direct one on the pituitary gland and PGE1 might release GH and prolactin, whereas IDM might have a direct action on the pituitary gland, and that blunt the release of these pituitary hormones induced by several stimuli."}
{"id": "PMID:193687", "title": "Diagnosis of insulin secreting tumour by retrograde pancreatography.", "content": "The case of a 26-year-old male with insulinoma is presented. An insulin secreting tumour was indicated by laboratory data. The tumour was accurately localized by endoscopic retrograde pancreatography, as verified by subsequent surgery.", "contents": "Diagnosis of insulin secreting tumour by retrograde pancreatography. The case of a 26-year-old male with insulinoma is presented. An insulin secreting tumour was indicated by laboratory data. The tumour was accurately localized by endoscopic retrograde pancreatography, as verified by subsequent surgery."}
{"id": "PMID:193688", "title": "Multicentric early gastric carcinoma mimicking type I (10 years after B-I-surgery).", "content": "10 YEARS AFTER B-I-partial gastrectomy for a proven benign gastric ulcer a multicentric early gastric carcinoma type II b, c was detected by endoscopy and histology. This early carcinoma differed from published cases in respect of its macroscopic classification, localization and expansion. The carcinoma situated next to the anastomosis invaded the duodenal mucosa. It also invaded a polypoid fold caused by the previous surgery, thus imitating an early gastric carcinoma type I.", "contents": "Multicentric early gastric carcinoma mimicking type I (10 years after B-I-surgery). 10 YEARS AFTER B-I-partial gastrectomy for a proven benign gastric ulcer a multicentric early gastric carcinoma type II b, c was detected by endoscopy and histology. This early carcinoma differed from published cases in respect of its macroscopic classification, localization and expansion. The carcinoma situated next to the anastomosis invaded the duodenal mucosa. It also invaded a polypoid fold caused by the previous surgery, thus imitating an early gastric carcinoma type I."}
{"id": "PMID:193690", "title": "Intrasplenic autotransplantation of canine pancreatic tissues. Maintenance of normoglycaemia after total pancreatectomy.", "content": "In mongrel dogs, the horizontal part of the pancreas was infiltrated with collagenase, cut in pieces, incubated with collagenase, rinsed twice by centrifugation or sedimentation, and implanted into the spleen of the same animal. The operations were terminated by the removal of the rest of the pancreas. Of 26 operated dogs, one died because of a duodenal perforation, five developed severe hyperglycaemia without remission, and 20 were long-term normoglycaemic survivors followed for up to 10 weeks. These 20 animals became spontaneously normoglycaemic in the course of the first 10 postoperative days. Later, during glucose loading tests, the pattern of blood sugar values was the same in the transplanted animals as in those of a group of non-operated dogs, but the insulin release, although immediate, attained half the control values. The plasma insulin in the splenic vein was more than seven times higher than in the peripheral circulation. Splenectomies performed in seven animals were followed by severe hyperglycaemia and death. Light and electron microscopy demonstrated the presence of the intact endocrine and exocrine pancreatic tissues in the spleens of all animals investigated. It is concluded that laborious separations of endocrine from exocrine tissue are not mandatory for ulterior endocrine function, and that in an animal larger than rodents it is possible to obtain a diabetes-preventing function after the transplantation of only a part of the gland.", "contents": "Intrasplenic autotransplantation of canine pancreatic tissues. Maintenance of normoglycaemia after total pancreatectomy. In mongrel dogs, the horizontal part of the pancreas was infiltrated with collagenase, cut in pieces, incubated with collagenase, rinsed twice by centrifugation or sedimentation, and implanted into the spleen of the same animal. The operations were terminated by the removal of the rest of the pancreas. Of 26 operated dogs, one died because of a duodenal perforation, five developed severe hyperglycaemia without remission, and 20 were long-term normoglycaemic survivors followed for up to 10 weeks. These 20 animals became spontaneously normoglycaemic in the course of the first 10 postoperative days. Later, during glucose loading tests, the pattern of blood sugar values was the same in the transplanted animals as in those of a group of non-operated dogs, but the insulin release, although immediate, attained half the control values. The plasma insulin in the splenic vein was more than seven times higher than in the peripheral circulation. Splenectomies performed in seven animals were followed by severe hyperglycaemia and death. Light and electron microscopy demonstrated the presence of the intact endocrine and exocrine pancreatic tissues in the spleens of all animals investigated. It is concluded that laborious separations of endocrine from exocrine tissue are not mandatory for ulterior endocrine function, and that in an animal larger than rodents it is possible to obtain a diabetes-preventing function after the transplantation of only a part of the gland."}
{"id": "PMID:193691", "title": "Thorotrast-induced renal tumours after retrograde pyelogram.", "content": "Seven cases of 'thorotrast kidney' after retrograde pyelogram with reflux are dealt with. In five instances cancer of the kidney developed, four of them obvious renal pelvic carcinoma between 14 and 41 years after the thorotrast pyelogram. In some cases the contrast deposits were misinterpreted and in one case the follow-up was also inadequate. There is a high risk of malignancy to connection with 'thorotrast kidneys'. These cases should be follewed up with intravenous pyelogram and exfoliative cytology from renal pelvis. Provided these tests are negative, nephro-ureterectomy should be put off.", "contents": "Thorotrast-induced renal tumours after retrograde pyelogram. Seven cases of 'thorotrast kidney' after retrograde pyelogram with reflux are dealt with. In five instances cancer of the kidney developed, four of them obvious renal pelvic carcinoma between 14 and 41 years after the thorotrast pyelogram. In some cases the contrast deposits were misinterpreted and in one case the follow-up was also inadequate. There is a high risk of malignancy to connection with 'thorotrast kidneys'. These cases should be follewed up with intravenous pyelogram and exfoliative cytology from renal pelvis. Provided these tests are negative, nephro-ureterectomy should be put off."}
{"id": "PMID:193695", "title": "Presynaptic alpha-adenoceptors: the depression of self-stimulation by clonidine and its restoration by piperoxane but not by phentolamine or phenoxybenzamine.", "content": "Depression of self-stimulation by clonidine has been ascribed to continuous direct stimulation of alpha-adrenoceptors with consequent disruption of reinforcement signals thought to be conveyed by noradrenergic pathways. This suggestion was tested by administration of alpha-receptor blocking agents (piperoxane, phentolamine and phenoxybenzamine, PBZ) differing in their affinity for pre- and post-synaptic receptor sites. Piperoxane in low doses (0.55-5.0 mg/kg) previously reported to cause specific blockade of pre-synaptic receptors implicated in negative feedback circuits, caused a significant increase in self-stimulation rate and strongly antagonized the depression of self-stimulation by clonidine (0.15 mg/kg). A larger dose of piperoxane (45 mg/kg) and graded doses of phentolamine and PBZ, affecting both pre- and post-synaptic receptors, depressed self-stimulation, and did not antagonize clonidine-induced depression of self-stimulation. It is concluded that depression of self-stimulation by clonidine may depend on clonidine-induced inhibition of NA release exerted via presynaptic receptors, and that the effect of clonidine is not necessarily evidence that noncontingent adrenergic stimulation disrupts reinforcement.", "contents": "Presynaptic alpha-adenoceptors: the depression of self-stimulation by clonidine and its restoration by piperoxane but not by phentolamine or phenoxybenzamine. Depression of self-stimulation by clonidine has been ascribed to continuous direct stimulation of alpha-adrenoceptors with consequent disruption of reinforcement signals thought to be conveyed by noradrenergic pathways. This suggestion was tested by administration of alpha-receptor blocking agents (piperoxane, phentolamine and phenoxybenzamine, PBZ) differing in their affinity for pre- and post-synaptic receptor sites. Piperoxane in low doses (0.55-5.0 mg/kg) previously reported to cause specific blockade of pre-synaptic receptors implicated in negative feedback circuits, caused a significant increase in self-stimulation rate and strongly antagonized the depression of self-stimulation by clonidine (0.15 mg/kg). A larger dose of piperoxane (45 mg/kg) and graded doses of phentolamine and PBZ, affecting both pre- and post-synaptic receptors, depressed self-stimulation, and did not antagonize clonidine-induced depression of self-stimulation. It is concluded that depression of self-stimulation by clonidine may depend on clonidine-induced inhibition of NA release exerted via presynaptic receptors, and that the effect of clonidine is not necessarily evidence that noncontingent adrenergic stimulation disrupts reinforcement."}
{"id": "PMID:193696", "title": "Discriminative and motor performance in rats after interference with dopamine neurotransmission with spiroperidol.", "content": "The disruption of instrumental conditioning after block of central dopamine neurotransmission with drugs or lesions has been explained as an inability to initiate movements rather than as a disruption of learning mechanisms per se. To further investigate this we have developed an under-water swim maze which is a test situation that partly counteracts the akinesia of the animals. The maze has been used to test the effect of dopamine receptor inhibition by spiroperidol on a brightness and a spatial discrimination task. Aquisition was blocked and the behaviour randomized after 0.05 mg/kg and higher doses. Swim speed, however, was not affected by 0.05 mg/kg. This suggests that spiroperidol affects the acquisition of this brightness discrimination task independently of its effects on motor performance. Spatial acquisition was not affected even at 5.0 mg/kg which shows that the deficit can not be generalized to all types of acquisition.", "contents": "Discriminative and motor performance in rats after interference with dopamine neurotransmission with spiroperidol. The disruption of instrumental conditioning after block of central dopamine neurotransmission with drugs or lesions has been explained as an inability to initiate movements rather than as a disruption of learning mechanisms per se. To further investigate this we have developed an under-water swim maze which is a test situation that partly counteracts the akinesia of the animals. The maze has been used to test the effect of dopamine receptor inhibition by spiroperidol on a brightness and a spatial discrimination task. Aquisition was blocked and the behaviour randomized after 0.05 mg/kg and higher doses. Swim speed, however, was not affected by 0.05 mg/kg. This suggests that spiroperidol affects the acquisition of this brightness discrimination task independently of its effects on motor performance. Spatial acquisition was not affected even at 5.0 mg/kg which shows that the deficit can not be generalized to all types of acquisition."}
{"id": "PMID:193697", "title": "Effect of indomethacin on the renal actions of theophylline.", "content": "The effects of theophylline ethylenediamine (15 mg/kg i.v.) on plasma renin activity (PRA), diuresis, creatinine clearance and plasma and urinary adenosine 3',5'-monophosphate (cyclic AMP) concentrations were studied in urethane-anaesthetized rabbits with and without pretreatment with indomethacin (5 mg/kg i.v.). Theophylline induced a several-fold increase in urinary sodium and water excretion, raised PRA from 76 +/- 15 TO 239 +/- 83 (S.E.M) ng/ml/h (p less than 0.05) and increased urinary cyclic AMP excretion from 0.21 +/- 0.04 to 0.50 +/- 0.08 nmol/min/kg/kidney (p less than 0.05) without any change in arterial plasma cyclic AMP concentration. The ratio between the clearance of creatinine and cyclic AMP was unchanged. After indomethacin pretreatment the theophylline-induced natriuresis was significantly reduced (p less than 0.05), while the effects of theophylline on PRA and urinary cyclic AMP excretion were unchanged. Under the present experimental conditions, indomethacin reduces renal prostaglandin biosynthesis by over 95%. our results indicate that prostaglandins might be concerned with the natriuretic effects of theophylline but not with the effect on PRA.", "contents": "Effect of indomethacin on the renal actions of theophylline. The effects of theophylline ethylenediamine (15 mg/kg i.v.) on plasma renin activity (PRA), diuresis, creatinine clearance and plasma and urinary adenosine 3',5'-monophosphate (cyclic AMP) concentrations were studied in urethane-anaesthetized rabbits with and without pretreatment with indomethacin (5 mg/kg i.v.). Theophylline induced a several-fold increase in urinary sodium and water excretion, raised PRA from 76 +/- 15 TO 239 +/- 83 (S.E.M) ng/ml/h (p less than 0.05) and increased urinary cyclic AMP excretion from 0.21 +/- 0.04 to 0.50 +/- 0.08 nmol/min/kg/kidney (p less than 0.05) without any change in arterial plasma cyclic AMP concentration. The ratio between the clearance of creatinine and cyclic AMP was unchanged. After indomethacin pretreatment the theophylline-induced natriuresis was significantly reduced (p less than 0.05), while the effects of theophylline on PRA and urinary cyclic AMP excretion were unchanged. Under the present experimental conditions, indomethacin reduces renal prostaglandin biosynthesis by over 95%. our results indicate that prostaglandins might be concerned with the natriuretic effects of theophylline but not with the effect on PRA."}
{"id": "PMID:193712", "title": "Serum cholinesterase: function in lipoprotein metabolism.", "content": "Human serum beta-lipoproteins, isolated by percipitation with heparin-calcium mixture, showed cholinesterase activity. The enzyme activity was almost proportional to the lipoprotein concentration. Rats, treated with neostigmine, a cholinesterase inhibitor, showed a significant decrease in serum beta-lipoprotein and in the incorporation of H3-lysine into the lipoprotein compared to untreated controls. The decreased incorporation of H3-lysine into beta-lipoprotein was associated with increased labelling of alpha-lopoprotein. There was no significant difference in the labelling of pre-beta-lipoprotein. We propose that LDL is formed from VLDL in the presence of cholinesterase.", "contents": "Serum cholinesterase: function in lipoprotein metabolism. Human serum beta-lipoproteins, isolated by percipitation with heparin-calcium mixture, showed cholinesterase activity. The enzyme activity was almost proportional to the lipoprotein concentration. Rats, treated with neostigmine, a cholinesterase inhibitor, showed a significant decrease in serum beta-lipoprotein and in the incorporation of H3-lysine into the lipoprotein compared to untreated controls. The decreased incorporation of H3-lysine into beta-lipoprotein was associated with increased labelling of alpha-lopoprotein. There was no significant difference in the labelling of pre-beta-lipoprotein. We propose that LDL is formed from VLDL in the presence of cholinesterase."}
{"id": "PMID:193725", "title": "[Comparative effect of chlorpromazine, imipramine and papaverine on the blood platelet function].", "content": "With a view of decoding the mechanisms of their action the effect of papaverine, chlorpromazine and imipramine produced on a number of blood platelets hemostatic functions was studied. All the three drugs suppress in a characteristic fashion the aggregation on blood platelets caused by thrombin in the Tyrode solution and in a plasma defibrilated by heating, as well as by collogen and ADP in the citrated plasma. Unlike chlorpromazine and imipramine papaverine exerts a strong inhibiting action on the phosphodiesterase activity. Chlorpromazine and imipramine suppress the absorption of serotonin and retraction more intensively than this is done by papaverine and call forth morphological changes in the blood platelets that proceed parallel with changes in the intensity of the photodiffusion and liberation of endogenous serotonin. It is postulated that chlorpromazine and imipramine manifest their inhibitory effect through nonspecific damage of the blood platelets membranes, whereas papaverine does this through exchange of adenine-nucleotides and, especially, of 3',5'-AMP.", "contents": "[Comparative effect of chlorpromazine, imipramine and papaverine on the blood platelet function]. With a view of decoding the mechanisms of their action the effect of papaverine, chlorpromazine and imipramine produced on a number of blood platelets hemostatic functions was studied. All the three drugs suppress in a characteristic fashion the aggregation on blood platelets caused by thrombin in the Tyrode solution and in a plasma defibrilated by heating, as well as by collogen and ADP in the citrated plasma. Unlike chlorpromazine and imipramine papaverine exerts a strong inhibiting action on the phosphodiesterase activity. Chlorpromazine and imipramine suppress the absorption of serotonin and retraction more intensively than this is done by papaverine and call forth morphological changes in the blood platelets that proceed parallel with changes in the intensity of the photodiffusion and liberation of endogenous serotonin. It is postulated that chlorpromazine and imipramine manifest their inhibitory effect through nonspecific damage of the blood platelets membranes, whereas papaverine does this through exchange of adenine-nucleotides and, especially, of 3',5'-AMP."}
{"id": "PMID:193737", "title": "Perifused adipose cells, quantitation and kinetics of lipolysis.", "content": "The perifused fat cell system is a system with which lipolytic activity can be monitored on a minute-to-minute basis. Thus, the rate at which lipolysis changes following the addition and removal of hormones can be followed. Catecholamines and other lipolytic agents produced a time-dependent increase in lipolysis following addition of agents, and a time-dependent decrease in lipolysis occurred following removal of the agent. ACTH also produced an increase in lipolysis. However, on termination of ACTH infusion, the lipolytic rate did not return to basal level but remained elevated for at least an additional 30 min (persistent phase). The persistent phase could be terminated by removal of Ca2+. Readdition of Ca2+ in the absence of additional ACTH resulted in a rapid increase in glycerol release. No persistant phase occurred following ACTH if the adipocytes were perifused in a Ca2+-free buffer. However, if Ca2+ was added to the system 20 min after termination of ACTH infusion, lipolysis increased to a rate greater than that obtained initially by infusing ACTH in a Ca2+-free buffer. It is concluded that ACTH is bound to some component of the fat cell in a Ca2+ independent, tenacious manner, and the full manifestation of that binding is dependent on the presence of Ca2+.", "contents": "Perifused adipose cells, quantitation and kinetics of lipolysis. The perifused fat cell system is a system with which lipolytic activity can be monitored on a minute-to-minute basis. Thus, the rate at which lipolysis changes following the addition and removal of hormones can be followed. Catecholamines and other lipolytic agents produced a time-dependent increase in lipolysis following addition of agents, and a time-dependent decrease in lipolysis occurred following removal of the agent. ACTH also produced an increase in lipolysis. However, on termination of ACTH infusion, the lipolytic rate did not return to basal level but remained elevated for at least an additional 30 min (persistent phase). The persistent phase could be terminated by removal of Ca2+. Readdition of Ca2+ in the absence of additional ACTH resulted in a rapid increase in glycerol release. No persistant phase occurred following ACTH if the adipocytes were perifused in a Ca2+-free buffer. However, if Ca2+ was added to the system 20 min after termination of ACTH infusion, lipolysis increased to a rate greater than that obtained initially by infusing ACTH in a Ca2+-free buffer. It is concluded that ACTH is bound to some component of the fat cell in a Ca2+ independent, tenacious manner, and the full manifestation of that binding is dependent on the presence of Ca2+."}
{"id": "PMID:193738", "title": "Regulation of triglyceride metabolism in the isotopically prelabeled perfused heart.", "content": "Utilization of 14C-prelabeled endogenous triglycerides was studied in isolated perfused working rat hearts. Lipolysis was estimated by the disappearance of 14C-labeled and total triglycerides. Metabolic 14CO2 production was continuously monitored to evaluate triglyceride fatty acid oxidation. Triglyceride utilization was enhanced by an increase in ventricular pressure development as evidenced by a faster rate of triglyceride mobilization and oxidation. Added catecholamines stimulated lipolysis in hearts perfused with glucose-containing buffer but were without effect in the presence of exogenous fatty acids; the latter were shown to be potent and, possibly, direct inhibitors of myocardial lipolysis. Mediation of catecholamine-induced lipolysis by cyclic AMP has not been settled. Dibutyryl cyclic AMP produced only a slight lipolytic effect, although theophylline, a known phosphodiesterase inhibitor, was a potent lipolytic agent. Theophylline may have exerted its lipolytic effect through an alternative mechanism. Hypoxia per se was a strong inhibitor of heart triglyceride utilization. Furthermore, added epinephrine was without effect on triglyceride lipolysis in hypoxic hearts. Thus, cardiac muscle triglyceride utilization is influenced by such factors as mechanical function, exogenous substrates, hormones, and oxygen availability. The mechanisms involved in these areas of regulation need to be resolved.", "contents": "Regulation of triglyceride metabolism in the isotopically prelabeled perfused heart. Utilization of 14C-prelabeled endogenous triglycerides was studied in isolated perfused working rat hearts. Lipolysis was estimated by the disappearance of 14C-labeled and total triglycerides. Metabolic 14CO2 production was continuously monitored to evaluate triglyceride fatty acid oxidation. Triglyceride utilization was enhanced by an increase in ventricular pressure development as evidenced by a faster rate of triglyceride mobilization and oxidation. Added catecholamines stimulated lipolysis in hearts perfused with glucose-containing buffer but were without effect in the presence of exogenous fatty acids; the latter were shown to be potent and, possibly, direct inhibitors of myocardial lipolysis. Mediation of catecholamine-induced lipolysis by cyclic AMP has not been settled. Dibutyryl cyclic AMP produced only a slight lipolytic effect, although theophylline, a known phosphodiesterase inhibitor, was a potent lipolytic agent. Theophylline may have exerted its lipolytic effect through an alternative mechanism. Hypoxia per se was a strong inhibitor of heart triglyceride utilization. Furthermore, added epinephrine was without effect on triglyceride lipolysis in hypoxic hearts. Thus, cardiac muscle triglyceride utilization is influenced by such factors as mechanical function, exogenous substrates, hormones, and oxygen availability. The mechanisms involved in these areas of regulation need to be resolved."}
{"id": "PMID:193739", "title": "Integration of lipid utilization with Krebs cycle activity in muscle.", "content": "This essay illustrates the ways in which beta-oxidation and the citric acid cycle interact. These included: 1) competition for CoASH, 2) competition for NAD+, and 3) competition for FADH2 oxidation. By means of the above, the cell is able to maintain a precise coordination between the activation of fatty acids in the cytosol, beta-oxidation in the mitochondria, and the complete oxidation of acetyl-CoA to CO2 via the citric acid cycle throughout a wide range of energy demands and oxygen availability.", "contents": "Integration of lipid utilization with Krebs cycle activity in muscle. This essay illustrates the ways in which beta-oxidation and the citric acid cycle interact. These included: 1) competition for CoASH, 2) competition for NAD+, and 3) competition for FADH2 oxidation. By means of the above, the cell is able to maintain a precise coordination between the activation of fatty acids in the cytosol, beta-oxidation in the mitochondria, and the complete oxidation of acetyl-CoA to CO2 via the citric acid cycle throughout a wide range of energy demands and oxygen availability."}
{"id": "PMID:193741", "title": "The effect of shearing of XC DNA on its RSV transfecting activity.", "content": "XC DNA fragments having the average molecular weight of 10(7) daltons were obtained by hydrodynamic shearing followed by sucrose gradient centrifugation or BUdR treatment of XC cells used for DNA preparation. Such DNA molecules, even after long-term storage, were found to be active in transfection.", "contents": "The effect of shearing of XC DNA on its RSV transfecting activity. XC DNA fragments having the average molecular weight of 10(7) daltons were obtained by hydrodynamic shearing followed by sucrose gradient centrifugation or BUdR treatment of XC cells used for DNA preparation. Such DNA molecules, even after long-term storage, were found to be active in transfection."}
{"id": "PMID:193742", "title": "The study of the rous virus synthesis in mammalian embryonic tissues growing in vitro.", "content": "The genome of Rous sarcoma virus was found in mouse and hamster embryo cells growing in vitro shortly after the infection and long before cell transformation occurred. The virus genome was not detected in embryo cells when they were treated with actinomycin D or when the temperature of incubation was lowered to +20 degrees C. This suggested that the synthesis of Rous virus genome could have taken place de novo in the cells investigated. Furthermore, the experiments showed that the life cycle of Rous virus in mammalian and avian cells had at least one phase in common, i.e., that sensitive to the action of actinomycin D.", "contents": "The study of the rous virus synthesis in mammalian embryonic tissues growing in vitro. The genome of Rous sarcoma virus was found in mouse and hamster embryo cells growing in vitro shortly after the infection and long before cell transformation occurred. The virus genome was not detected in embryo cells when they were treated with actinomycin D or when the temperature of incubation was lowered to +20 degrees C. This suggested that the synthesis of Rous virus genome could have taken place de novo in the cells investigated. Furthermore, the experiments showed that the life cycle of Rous virus in mammalian and avian cells had at least one phase in common, i.e., that sensitive to the action of actinomycin D."}
{"id": "PMID:193743", "title": "A double-blind comparative study of Otoseptil Ear Drops and Otosporin Ear Drops in otitis externa.", "content": "A double-blind comparative study of Otoseptil Ear Drops and Otosporin Ear Drops in otitis externa in fifty-eight patients revealed them both to be equally effective in a series with very few fungal infections. In view of the normally high proportion of infections including fungi, there are obvious advantages in using Otoseptil Ear Drops.", "contents": "A double-blind comparative study of Otoseptil Ear Drops and Otosporin Ear Drops in otitis externa. A double-blind comparative study of Otoseptil Ear Drops and Otosporin Ear Drops in otitis externa in fifty-eight patients revealed them both to be equally effective in a series with very few fungal infections. In view of the normally high proportion of infections including fungi, there are obvious advantages in using Otoseptil Ear Drops."}
{"id": "PMID:193745", "title": "Statistical evaluation of polygraphic investigations of pentoxifylline.", "content": "Changes in the electro-encephalogram, and in the electro-oculogram electromyogram, ECG, blood supply, blood pressure, electrical skin activity and neurological/psychiatric findings, were investigated in 100 patients given single administrations of 200 mg of pentoxifylline (BL 191). It is concluded from the changes in the EEG wave patterns that pentoxifylline produces a beneficial effect on the cerebral processes contributing to bio-electrical brain activity. Pentoxifylline can be classed as a substance with microcirculatory/metabolic effects on the brain, which lead to stimulation of psychomotor behaviour.", "contents": "Statistical evaluation of polygraphic investigations of pentoxifylline. Changes in the electro-encephalogram, and in the electro-oculogram electromyogram, ECG, blood supply, blood pressure, electrical skin activity and neurological/psychiatric findings, were investigated in 100 patients given single administrations of 200 mg of pentoxifylline (BL 191). It is concluded from the changes in the EEG wave patterns that pentoxifylline produces a beneficial effect on the cerebral processes contributing to bio-electrical brain activity. Pentoxifylline can be classed as a substance with microcirculatory/metabolic effects on the brain, which lead to stimulation of psychomotor behaviour."}
{"id": "PMID:193748", "title": "Visual stimulation and wake-sleep behavior in human neonates.", "content": "Sixteen male and 16 female infants were exposed to 1 of 4 visual stimulus conditions during pre- and postprandial wakefulness. Whereas a nonpatterned gray stimulus minimized the amount of alert inactivity and maximized the amount of subsequent rapid eye movement (REM) sleep, black-and-white checkerboard patterned stimuli produced greater amounts of alert inactivity and correspondingly lesser amounts of subsequent REM sleep. Amounts of alert inactivity and of subsequent REM sleep produced by the checkerboard patterns depended upon pattern size, infant gender, and stimulus presentation strategy. Inversely correlated stimulus control of wakefulness and subsequent REM sleep was proposed as the functional basis of the inversely correlated ontogenesis of wakefulness and REM sleep.", "contents": "Visual stimulation and wake-sleep behavior in human neonates. Sixteen male and 16 female infants were exposed to 1 of 4 visual stimulus conditions during pre- and postprandial wakefulness. Whereas a nonpatterned gray stimulus minimized the amount of alert inactivity and maximized the amount of subsequent rapid eye movement (REM) sleep, black-and-white checkerboard patterned stimuli produced greater amounts of alert inactivity and correspondingly lesser amounts of subsequent REM sleep. Amounts of alert inactivity and of subsequent REM sleep produced by the checkerboard patterns depended upon pattern size, infant gender, and stimulus presentation strategy. Inversely correlated stimulus control of wakefulness and subsequent REM sleep was proposed as the functional basis of the inversely correlated ontogenesis of wakefulness and REM sleep."}
{"id": "PMID:193752", "title": "Role of DNA repair in natural resistance of rat ascites hepatomas to nitrogen mustard.", "content": "Mechanism of natural resistance of rat ascites hepatomas to nitrogen mustard was examined with tumors, especially AH-13 and AH-44, sensitive and resistant to the chemical, respectively. There was found little difference in the uptake and binding of the chemical among the two lines. In contrast, DNA repair activity of the resistant line was higher than that of the sensitive line. This result suggested that natural resistance of AH-44 to the drug may be, at least partially, due to its higher activity of repairing DNA damage.", "contents": "Role of DNA repair in natural resistance of rat ascites hepatomas to nitrogen mustard. Mechanism of natural resistance of rat ascites hepatomas to nitrogen mustard was examined with tumors, especially AH-13 and AH-44, sensitive and resistant to the chemical, respectively. There was found little difference in the uptake and binding of the chemical among the two lines. In contrast, DNA repair activity of the resistant line was higher than that of the sensitive line. This result suggested that natural resistance of AH-44 to the drug may be, at least partially, due to its higher activity of repairing DNA damage."}
{"id": "PMID:193753", "title": "A case of minimal deviation hepatoma in man with elevated liver-type pyruvate kinase isozyme.", "content": "A surgical specimen of solitary, encapsulated tumor tissue obtained from a 52-year-old male, diagnosed histologically as well-differentiated hepatocellular carcinoma (Grade II, Edmondson and Steiner) with liver cirrhosis, Type A' (and B is some parts), was found to have a supernormal level of pyruvate kinase Type L and subnormal level of Type M2; the activities (units/mg protein) being 1.21 and 0.12 respectively. The resulting isozyme pattern was apparently \"superdifferentiated\" as compared with those of not only the tumor-bearing, cirrhotic liver (Type L, 0.19; Type M2, 0.67) but also the normal liver (Type L, 0.47+/-0.05; Type M2, 0.18+/-0.02). The electrophoretic and kinetic properties of the type L isozyme were identical with those of the cirrhotic host liver and a non-cirrhotic control liver. Other enzyme levels in the hepatoma tissue were as follows: Glucose-6-phosphatase, norma; fructose-1,6-bisphosphatase, reduced; glucokinase, absent; and hexokinase Types I and III, and glucose-6-phosphate dehydrogenase, slightly increased. The serum alpha-fetoprotein level was 95 ng/ml. The whole enzyme profile is consistent with the minimal deviation hepatomas in rats. The results were compared with those of other human hepatomas, and the mechanisms of disordered regulation in hepatoma gene expression were discussed.", "contents": "A case of minimal deviation hepatoma in man with elevated liver-type pyruvate kinase isozyme. A surgical specimen of solitary, encapsulated tumor tissue obtained from a 52-year-old male, diagnosed histologically as well-differentiated hepatocellular carcinoma (Grade II, Edmondson and Steiner) with liver cirrhosis, Type A' (and B is some parts), was found to have a supernormal level of pyruvate kinase Type L and subnormal level of Type M2; the activities (units/mg protein) being 1.21 and 0.12 respectively. The resulting isozyme pattern was apparently \"superdifferentiated\" as compared with those of not only the tumor-bearing, cirrhotic liver (Type L, 0.19; Type M2, 0.67) but also the normal liver (Type L, 0.47+/-0.05; Type M2, 0.18+/-0.02). The electrophoretic and kinetic properties of the type L isozyme were identical with those of the cirrhotic host liver and a non-cirrhotic control liver. Other enzyme levels in the hepatoma tissue were as follows: Glucose-6-phosphatase, norma; fructose-1,6-bisphosphatase, reduced; glucokinase, absent; and hexokinase Types I and III, and glucose-6-phosphate dehydrogenase, slightly increased. The serum alpha-fetoprotein level was 95 ng/ml. The whole enzyme profile is consistent with the minimal deviation hepatomas in rats. The results were compared with those of other human hepatomas, and the mechanisms of disordered regulation in hepatoma gene expression were discussed."}
{"id": "PMID:193754", "title": "Relationship between transcerebral passage of tumor cells and brain metastasis.", "content": "Quantitative study was carried out on transcerebral passage of tumor cells using Yoshida sarcoma and 6 strains of rat ascites hepatoma. The counting was done every second for 40 sec. In relation to the results obtained, histological study was made on the cerebral metastasis of these tumor cells. Metastatic foci in the brain parenchyma, except the meninges and choroid plexus, were formed by island-forming strains (AH-130, AH-272, and AH-7971) which showed comparatively low passage rate and not be single-cell strains (Yoshida sarcoma, AH-7974F, AH-66F, and AH-13) which showed comparatively high rates. Accordingly, it is obvious that there is a correlation between transcerebral passage rates and brain metastasis formation. The mechanisms of metastasis formation were discussed with special reference to arrest of tumor cells in blood vessels.", "contents": "Relationship between transcerebral passage of tumor cells and brain metastasis. Quantitative study was carried out on transcerebral passage of tumor cells using Yoshida sarcoma and 6 strains of rat ascites hepatoma. The counting was done every second for 40 sec. In relation to the results obtained, histological study was made on the cerebral metastasis of these tumor cells. Metastatic foci in the brain parenchyma, except the meninges and choroid plexus, were formed by island-forming strains (AH-130, AH-272, and AH-7971) which showed comparatively low passage rate and not be single-cell strains (Yoshida sarcoma, AH-7974F, AH-66F, and AH-13) which showed comparatively high rates. Accordingly, it is obvious that there is a correlation between transcerebral passage rates and brain metastasis formation. The mechanisms of metastasis formation were discussed with special reference to arrest of tumor cells in blood vessels."}
{"id": "PMID:193755", "title": "Altered growth behavior of virus-transformed cells after treatment with dextran sulfate.", "content": "Growth behavior in vitro of 3T3 cells and the cells transformed by polyoma or SV40 virus was studied after their treatment with dextran sulfate. The transformed cells treated with dextran sulfated showed decreased saturation density compared with untreated cells, whereas saturation density of 3T3 cells was hardly affected by treatment with dextran sulfate. The ratio of saturation density of untreated SV3T3 cells to that of the treated cells was 64.1% at 5 microng/ml and was 43.4% at 10 microng/ml of dextran sulfate. In Py3T3 cells the ratio was 45.0% at both concentrations of 10 and 20 microng/ml. Plating efficiency was not affected in 3 cell lines tested after treatment with dextran sulfate. The treated cells showed a tendency to form thin and not piled-up colonies in the central area. The treated SV3T3 and Py3T3 cells were flattened in shape compared with the untreated cells. In agar medium the treated SU 3T3 and Py 3T3 cells showed the tendency to stop growing after forming small colonies, whereas the untreated cells kept growing anf formed large colonies. These results suggested that dextran sulfate altered temporarily the growth of the transformed cells to that of untransformed cells.", "contents": "Altered growth behavior of virus-transformed cells after treatment with dextran sulfate. Growth behavior in vitro of 3T3 cells and the cells transformed by polyoma or SV40 virus was studied after their treatment with dextran sulfate. The transformed cells treated with dextran sulfated showed decreased saturation density compared with untreated cells, whereas saturation density of 3T3 cells was hardly affected by treatment with dextran sulfate. The ratio of saturation density of untreated SV3T3 cells to that of the treated cells was 64.1% at 5 microng/ml and was 43.4% at 10 microng/ml of dextran sulfate. In Py3T3 cells the ratio was 45.0% at both concentrations of 10 and 20 microng/ml. Plating efficiency was not affected in 3 cell lines tested after treatment with dextran sulfate. The treated cells showed a tendency to form thin and not piled-up colonies in the central area. The treated SV3T3 and Py3T3 cells were flattened in shape compared with the untreated cells. In agar medium the treated SU 3T3 and Py 3T3 cells showed the tendency to stop growing after forming small colonies, whereas the untreated cells kept growing anf formed large colonies. These results suggested that dextran sulfate altered temporarily the growth of the transformed cells to that of untransformed cells."}
{"id": "PMID:193756", "title": "Infectious murine type-C viruses released from human cancer cells transplated into nude mice.", "content": "Type-C virus particles were revealed by electron microscope in 6 of 9 tumours of cultured and biopsied human cancers heterotransplanted into nude mice. Some tumours in nude mice were explanted for in vitro cultivation. The virus particles were also found in the cultures derived from the virus-positive tumors. They were mostly found extracellularly, but the particles in budding process were also encountered frequently. Cytological study and karyotype analysis of the cultured cells proved these virus-releasing cells as of hus of human origin. From the close correlation between the statistical virus counts and the complement fixation titers for murine gs antigen of the tumors and their cultures, these viruses propagated in human cancer cells were confirmed to be infectious viruses of nude mouse origin. The virus replicating in human cancer cells was readily infected in some of innocent human cancer cells by co-cultivation. It is to be emphasized that infection of animal endogenous viruses on heterotransplanted human cancer cells is a bothersome contamination for human cancer research, especially when searching for a human tumor virus candidate.", "contents": "Infectious murine type-C viruses released from human cancer cells transplated into nude mice. Type-C virus particles were revealed by electron microscope in 6 of 9 tumours of cultured and biopsied human cancers heterotransplanted into nude mice. Some tumours in nude mice were explanted for in vitro cultivation. The virus particles were also found in the cultures derived from the virus-positive tumors. They were mostly found extracellularly, but the particles in budding process were also encountered frequently. Cytological study and karyotype analysis of the cultured cells proved these virus-releasing cells as of hus of human origin. From the close correlation between the statistical virus counts and the complement fixation titers for murine gs antigen of the tumors and their cultures, these viruses propagated in human cancer cells were confirmed to be infectious viruses of nude mouse origin. The virus replicating in human cancer cells was readily infected in some of innocent human cancer cells by co-cultivation. It is to be emphasized that infection of animal endogenous viruses on heterotransplanted human cancer cells is a bothersome contamination for human cancer research, especially when searching for a human tumor virus candidate."}
{"id": "PMID:193757", "title": "Liver protocollagen proline hydroxylase in human liver diseases and experimental liver fibrosis.", "content": "Liver protocallagen proline hydroxylase activity (PPH activity) was determined in patients with various liver diseases, CCl4-induced liver fibrosis rats and cholin deficiency (tcd) fatty liver rats. The following results were obtained: Liver PPH activity in patients with chronic hepatitis was higher than that in patients with acute hepatitis, while the activity in patients with liver cirrhosis was much higher than that in patients with chronic hepatitis. The activity was higher in patients with chronic active hepatitis than in those with chronic inactive hepatitis. Patients with active and progressive liver cirrhosis were found to have an especially high PPH activity, in whom the activity reflected well the degree of liver fibrosis. Even though fibrosis in persistent hepatitis was almost negligible or slight, the degree of liver PPH activity in persistent hepatitis was similar to that in liver cirrhosis. Liver PPH activities in CCl4-induced liver fibrosis rats and CD fatty liver rats elevated proportionally to the lapse of time. Whilst liver PPH activity in rats of CD fatty liver without fibrosis in 23 to 31 weeks after the start of the experiment was slightly lower than that in rats of CD fatty liver with fibrosis. But liver PPH activity of the former was considerably higher than that of control rats.", "contents": "Liver protocollagen proline hydroxylase in human liver diseases and experimental liver fibrosis. Liver protocallagen proline hydroxylase activity (PPH activity) was determined in patients with various liver diseases, CCl4-induced liver fibrosis rats and cholin deficiency (tcd) fatty liver rats. The following results were obtained: Liver PPH activity in patients with chronic hepatitis was higher than that in patients with acute hepatitis, while the activity in patients with liver cirrhosis was much higher than that in patients with chronic hepatitis. The activity was higher in patients with chronic active hepatitis than in those with chronic inactive hepatitis. Patients with active and progressive liver cirrhosis were found to have an especially high PPH activity, in whom the activity reflected well the degree of liver fibrosis. Even though fibrosis in persistent hepatitis was almost negligible or slight, the degree of liver PPH activity in persistent hepatitis was similar to that in liver cirrhosis. Liver PPH activities in CCl4-induced liver fibrosis rats and CD fatty liver rats elevated proportionally to the lapse of time. Whilst liver PPH activity in rats of CD fatty liver without fibrosis in 23 to 31 weeks after the start of the experiment was slightly lower than that in rats of CD fatty liver with fibrosis. But liver PPH activity of the former was considerably higher than that of control rats."}
{"id": "PMID:193760", "title": "Mediation of guinea pig gastric secretion in vitro by cyclic nucleotides.", "content": "The effect of methacholine, theophylline, and cyclic adenyl and guanyl nucleotides on gastric secretion from antral and proximal duodenal mucosa of the guinea pig was studied. Both 2 mM dibutyryl (db) cAMP and 5 mM theophylline produced significant increases in gastrin secretion, 4.3 +/- 0.7 (P less than 0.001) and 9.3  +/- 2.4 pg mg-1 min-1 (P less than 0.005) respectively, above basal gastrin secretion (1.5 +/- 0.4 pg mg-1 min-1). The combined effect of the two agents was additive (14.5 +/- 3.6 pg mg-1 min-1). Db cGMP (2 mM) had no effect on gastrin secretion. Methacholine produced a dose-related increase in gastrin secretion which at maximum equaled the combined effect of theophylline and db cAMP. The results suggest that gastrin secretion is mediated in part by intracellular cAMP but do not exclude a cooperative involvement of cGMP.", "contents": "Mediation of guinea pig gastric secretion in vitro by cyclic nucleotides. The effect of methacholine, theophylline, and cyclic adenyl and guanyl nucleotides on gastric secretion from antral and proximal duodenal mucosa of the guinea pig was studied. Both 2 mM dibutyryl (db) cAMP and 5 mM theophylline produced significant increases in gastrin secretion, 4.3 +/- 0.7 (P less than 0.001) and 9.3  +/- 2.4 pg mg-1 min-1 (P less than 0.005) respectively, above basal gastrin secretion (1.5 +/- 0.4 pg mg-1 min-1). The combined effect of the two agents was additive (14.5 +/- 3.6 pg mg-1 min-1). Db cGMP (2 mM) had no effect on gastrin secretion. Methacholine produced a dose-related increase in gastrin secretion which at maximum equaled the combined effect of theophylline and db cAMP. The results suggest that gastrin secretion is mediated in part by intracellular cAMP but do not exclude a cooperative involvement of cGMP."}
{"id": "PMID:193761", "title": "Effects of calcitonin and substance P on the transport of Ca, Na and Cl across rat ileum in vitro.", "content": "Both salmon calcitonin (SCT) and substance P decreased ileal Na absorption, changed Cl transport from net absorption to net secretion and elevated the short circuit current when added in vitro at concentrations of 10 microng per ml to solutions bathing the serosal surface of rat ileum which had been stripped of its serosal muscle coat. The effects of substance P were of greater magnitude but shorter duration than SCT. Both peptides also increased the bidirectional fluxes of Ca but did not alter net Ca movement. The changes in Na and Cl fluxes and short circuit current are identifical to those which occur when cellular levels of cyclic AMP increased. However, incubation of ileal mucosa with SCT or substance P did not cause a detectable change in cellular levels of cyclic AMP or cyclic GMP. Both the mechanism of action and the possible physiological functions of SCT and substance P in the regulation of electrolyte transport require further investigation. The results with SCT appear to confirm prior suggestions that calcitonin may act directly to produce secretory diarrhea under pathophysiological conditions.", "contents": "Effects of calcitonin and substance P on the transport of Ca, Na and Cl across rat ileum in vitro. Both salmon calcitonin (SCT) and substance P decreased ileal Na absorption, changed Cl transport from net absorption to net secretion and elevated the short circuit current when added in vitro at concentrations of 10 microng per ml to solutions bathing the serosal surface of rat ileum which had been stripped of its serosal muscle coat. The effects of substance P were of greater magnitude but shorter duration than SCT. Both peptides also increased the bidirectional fluxes of Ca but did not alter net Ca movement. The changes in Na and Cl fluxes and short circuit current are identifical to those which occur when cellular levels of cyclic AMP increased. However, incubation of ileal mucosa with SCT or substance P did not cause a detectable change in cellular levels of cyclic AMP or cyclic GMP. Both the mechanism of action and the possible physiological functions of SCT and substance P in the regulation of electrolyte transport require further investigation. The results with SCT appear to confirm prior suggestions that calcitonin may act directly to produce secretory diarrhea under pathophysiological conditions."}
{"id": "PMID:193763", "title": "A cytogenetic analysis of cyclic nucleotide phosphodiesterase activities in Drosophila.", "content": "The genome of Drosophila melanogaster has been surveyed for chromosomal regions which exert a dosage effect on the activities of cAMP phosphodiesterase or cGMP phosphodiesterase. Two regions increase cAMP phosphodiesterase activity when present as duplications. A region of the X chromosome increases cAMP phosphodiesterase activity when duplicated and decreases that activity when deficient. This region has been delimited to chromomeres 3D3 and 3D4, with 3D4 being the most probable locus, and may contain a structural gene for cAMP phosphodiesterase. A region on the third chromosome, 90E-91B, increases cAMP phosphodiesterase activity when duplicated but has no effect on the activity when deficient. Two regions increase cGMP phosphodiesterase activity when present as duplications. A region of the X chromosome, 5D-9C, increases cGMP phosphodiesterase activity when duplicated, but smaller duplications covering this region fail to show such an increase, indicating that a single locus is not responsible for the increase observed for the larger duplication. A region of the third chromosome, 88C-91B, also increases cGMP phosphodiesterase activity when duplicated. Smaller duplications covering this region show smaller increases than that observed for the larger duplication, suggesting that at least three loci between 88C and 91B contribute to the observed increase by that region. Deficiencies covering region 88C-91B do not affect cGMP phosphodiesterase activity. No locus for a presumptive structural gene for cGMP phosphodiesterase has been found. Limitations of the use of segmental aneuploidy in locating structural genes for enzymes are discussed.", "contents": "A cytogenetic analysis of cyclic nucleotide phosphodiesterase activities in Drosophila. The genome of Drosophila melanogaster has been surveyed for chromosomal regions which exert a dosage effect on the activities of cAMP phosphodiesterase or cGMP phosphodiesterase. Two regions increase cAMP phosphodiesterase activity when present as duplications. A region of the X chromosome increases cAMP phosphodiesterase activity when duplicated and decreases that activity when deficient. This region has been delimited to chromomeres 3D3 and 3D4, with 3D4 being the most probable locus, and may contain a structural gene for cAMP phosphodiesterase. A region on the third chromosome, 90E-91B, increases cAMP phosphodiesterase activity when duplicated but has no effect on the activity when deficient. Two regions increase cGMP phosphodiesterase activity when present as duplications. A region of the X chromosome, 5D-9C, increases cGMP phosphodiesterase activity when duplicated, but smaller duplications covering this region fail to show such an increase, indicating that a single locus is not responsible for the increase observed for the larger duplication. A region of the third chromosome, 88C-91B, also increases cGMP phosphodiesterase activity when duplicated. Smaller duplications covering this region show smaller increases than that observed for the larger duplication, suggesting that at least three loci between 88C and 91B contribute to the observed increase by that region. Deficiencies covering region 88C-91B do not affect cGMP phosphodiesterase activity. No locus for a presumptive structural gene for cGMP phosphodiesterase has been found. Limitations of the use of segmental aneuploidy in locating structural genes for enzymes are discussed."}
{"id": "PMID:193764", "title": "The consequences of nullosomy for a chromosomal region affecting cyclic AMP phosphodiesterase activity in Drosophila.", "content": "A study of Drosophila nullosomic for chromomere 3D4 shows that this region of the genome is necessary for male fertility, normal female fertility and normal oogenesis. Males nullosomic for 3D4 lack normal, motile sperm. Females nullosomic for this region exert a maternal influence on their progeny which results in a diversity of imaginal defects. The observation that chromomere 3D4 is the most probable locus for a chromosomal region which affects cAMP phosphodiesterase activity, and which may contain a structural gene for the enzyme, prompts the hypothesis that the diverse physiological effects caused by nullosomy for 3D4 are the result of an aberrant cAMP metabolism.", "contents": "The consequences of nullosomy for a chromosomal region affecting cyclic AMP phosphodiesterase activity in Drosophila. A study of Drosophila nullosomic for chromomere 3D4 shows that this region of the genome is necessary for male fertility, normal female fertility and normal oogenesis. Males nullosomic for 3D4 lack normal, motile sperm. Females nullosomic for this region exert a maternal influence on their progeny which results in a diversity of imaginal defects. The observation that chromomere 3D4 is the most probable locus for a chromosomal region which affects cAMP phosphodiesterase activity, and which may contain a structural gene for the enzyme, prompts the hypothesis that the diverse physiological effects caused by nullosomy for 3D4 are the result of an aberrant cAMP metabolism."}
{"id": "PMID:193766", "title": "The effect of environmental factors of the coking plant on the enzymatic activity of rabbit oral mucosa.", "content": "Histochemical methods were used to investigate the activities of some intracellular enzymes in the oral mucosa of the rabbits which had been kept in selected work-stands of a coking-plant for 3 months. The findings were compared with the results for the enzymatic activity of the oral mucosa of control rabbits. The epithelium of the oral mucosa of the experimental rabbits was found to be proliferated acanthotically; moreover, there occurred some other morphological changes of the mucosa which often resembled precancerous states of leukoplakia type. In comparison with the control group, the activities of the studied enzymes, i.e. reduced NAD dehydrogenase (NADD), glucose-6-phosphate dehydrogenase (G6PD), lactate dehydrogenase (LDS), succinate dehydrogenase (SD), cytochrome oxidase (CO), and phosphorylase a+b in the epithelium and the connective-tissue cells of the studied mucosa of the experimental animals were as a rule markedly lowered, this decline being especially pronounced for the three last-mentioned enzymes. It was only the proliferating stratum basale of the experimental rabbit epithelium that frequently exhibited enhanced activities of NADD and LDS. Besides, the activities of NADD, G6PD and LDS were of a markedly diverse intensity in the cells of the chaotically proliferating stratum spinosum of the experimental rabbit mucosa. The results point to the noxious modifying effect of chemical and physical agents of the investigated environment on the oral mucosa of the animals studied.", "contents": "The effect of environmental factors of the coking plant on the enzymatic activity of rabbit oral mucosa. Histochemical methods were used to investigate the activities of some intracellular enzymes in the oral mucosa of the rabbits which had been kept in selected work-stands of a coking-plant for 3 months. The findings were compared with the results for the enzymatic activity of the oral mucosa of control rabbits. The epithelium of the oral mucosa of the experimental rabbits was found to be proliferated acanthotically; moreover, there occurred some other morphological changes of the mucosa which often resembled precancerous states of leukoplakia type. In comparison with the control group, the activities of the studied enzymes, i.e. reduced NAD dehydrogenase (NADD), glucose-6-phosphate dehydrogenase (G6PD), lactate dehydrogenase (LDS), succinate dehydrogenase (SD), cytochrome oxidase (CO), and phosphorylase a+b in the epithelium and the connective-tissue cells of the studied mucosa of the experimental animals were as a rule markedly lowered, this decline being especially pronounced for the three last-mentioned enzymes. It was only the proliferating stratum basale of the experimental rabbit epithelium that frequently exhibited enhanced activities of NADD and LDS. Besides, the activities of NADD, G6PD and LDS were of a markedly diverse intensity in the cells of the chaotically proliferating stratum spinosum of the experimental rabbit mucosa. The results point to the noxious modifying effect of chemical and physical agents of the investigated environment on the oral mucosa of the animals studied."}
{"id": "PMID:193767", "title": "[Effects of several catecholamine-related drugs on aggressive behavior, brain noradrenaline content and tyramine uptake by isolated mice].", "content": "Such effects were studied in male albino mice maintained under isolation circumstances for 7 weeks in order to induce aggressiveness. L-DOPA (25 mg/kg) was given concomitantly with DDC (75 mg/kg) or reserpine (0.1 mg/kg), or each was administered signly and intraperitoneally to subjects twice weekly. Two peaks on the aggressive degree were observed at the 3rd-4th and 6th weeks, respectively. At the first peak, mice treated with L-DOPA and/or reserpine demonstrated aggressive behavior to a higher degree than control mice but at the second peak, to a lower degree. Mice treated with L-DOPA and DDC showed the highest degree at the second peak. Tyramine uptake in the brain measured at the 6th week was enhanced in mice treated with combinations of L-DOPA with reserpine or DDC. Noradrenaline content in the brain was lowered in mice treated with L-DOPA and/or reserpine, in comparison with each control value; It is thus concluded that catecholamine-related drugs influence the degree of enhancement of aggressiveness in modes which vary depending on the form of action of each drug.", "contents": "[Effects of several catecholamine-related drugs on aggressive behavior, brain noradrenaline content and tyramine uptake by isolated mice]. Such effects were studied in male albino mice maintained under isolation circumstances for 7 weeks in order to induce aggressiveness. L-DOPA (25 mg/kg) was given concomitantly with DDC (75 mg/kg) or reserpine (0.1 mg/kg), or each was administered signly and intraperitoneally to subjects twice weekly. Two peaks on the aggressive degree were observed at the 3rd-4th and 6th weeks, respectively. At the first peak, mice treated with L-DOPA and/or reserpine demonstrated aggressive behavior to a higher degree than control mice but at the second peak, to a lower degree. Mice treated with L-DOPA and DDC showed the highest degree at the second peak. Tyramine uptake in the brain measured at the 6th week was enhanced in mice treated with combinations of L-DOPA with reserpine or DDC. Noradrenaline content in the brain was lowered in mice treated with L-DOPA and/or reserpine, in comparison with each control value; It is thus concluded that catecholamine-related drugs influence the degree of enhancement of aggressiveness in modes which vary depending on the form of action of each drug."}
{"id": "PMID:193768", "title": "Study on the partial differential REM deprivation (PDRD).", "content": "With an aim to make observations on the rebound elevation of REM sleep, we have devised the partial differential REM deprivation (PDRD) method whereby the subjects are awakened forciby at a fixed time early in the morning. By this method, REM sleep is deprivated by about a half and stage 2 sleep by about one third of the baseline value; but stage SWS is not deprivated. When the test set of PDRD is performed repeatedly on an identical subject, the REM sleep time during PDRD night and recovery night is almost always constant. Our PDRD, we believe, is an excellent method that relieves the disconfort of the subject and the physical burden of research workers and yet is capable of measuring almost accurately the magnitude of rebound elevation of REM sleep in each subject.", "contents": "Study on the partial differential REM deprivation (PDRD). With an aim to make observations on the rebound elevation of REM sleep, we have devised the partial differential REM deprivation (PDRD) method whereby the subjects are awakened forciby at a fixed time early in the morning. By this method, REM sleep is deprivated by about a half and stage 2 sleep by about one third of the baseline value; but stage SWS is not deprivated. When the test set of PDRD is performed repeatedly on an identical subject, the REM sleep time during PDRD night and recovery night is almost always constant. Our PDRD, we believe, is an excellent method that relieves the disconfort of the subject and the physical burden of research workers and yet is capable of measuring almost accurately the magnitude of rebound elevation of REM sleep in each subject."}
{"id": "PMID:193769", "title": "[Clinical and histopathological studies of cases of lafora-like inclusion bodies].", "content": "In case 1, 41-year-old male, developed progressive demetia, paretic gait disturbance and pyramidal signs with the duration of three years. The neuropathological study revealed systemic atrophy as type Pick-disease i.e., lobal atrophy in the frontal and the parieto-occipital regions, degenerative changes in the basal ganglia and in the thalamus, nerve cell loss in the substantia nigra and myelin pallor in the pyramidal tract. Lafora-like inclusions were found in the cerebral cortex and in the cochleal nucleus. In case 2, 45-year-old male, showed character change, cerebellar symptomes and mental deteriotation, and ulcers on the oral mucosa during about 15 years long period. Neuropathological examination showed chronic encephalitis in the brain stem, vacuolar change in the neuron in the olivary nucleus and Lafora-like inclusions in the cochlear nucleus. Though neither generalized conversion nor myoclonus were clinicaly observed in these cases, the inclusions showed histochemically strong similarity with that of the Lafora-disease. These Lafora-like inclusions were compared with those in the literatur, which were reported on various disease of CNS. Finally in respect of predilection of the inclusions, it is likely that the inclusions result from same metabolic disturbance in the cochlear neurons in the Lafora-disease as well as in the present cases.", "contents": "[Clinical and histopathological studies of cases of lafora-like inclusion bodies]. In case 1, 41-year-old male, developed progressive demetia, paretic gait disturbance and pyramidal signs with the duration of three years. The neuropathological study revealed systemic atrophy as type Pick-disease i.e., lobal atrophy in the frontal and the parieto-occipital regions, degenerative changes in the basal ganglia and in the thalamus, nerve cell loss in the substantia nigra and myelin pallor in the pyramidal tract. Lafora-like inclusions were found in the cerebral cortex and in the cochleal nucleus. In case 2, 45-year-old male, showed character change, cerebellar symptomes and mental deteriotation, and ulcers on the oral mucosa during about 15 years long period. Neuropathological examination showed chronic encephalitis in the brain stem, vacuolar change in the neuron in the olivary nucleus and Lafora-like inclusions in the cochlear nucleus. Though neither generalized conversion nor myoclonus were clinicaly observed in these cases, the inclusions showed histochemically strong similarity with that of the Lafora-disease. These Lafora-like inclusions were compared with those in the literatur, which were reported on various disease of CNS. Finally in respect of predilection of the inclusions, it is likely that the inclusions result from same metabolic disturbance in the cochlear neurons in the Lafora-disease as well as in the present cases."}
{"id": "PMID:193770", "title": "[Blood protein synthesis in isolated liver cells].", "content": "Cells obtained by continuous perfusion with collagenase maintained their ultrastructure and their capacity for protein synthesis in contrast to mechanically isolated rat liver cells. Albumin and angiotensinogen (renin substrate) are synthesized and secreted and the synthesis of both proteins is stimulated by addition of hydrocortisone. As cell suspensions allow the simultaneous investigation of several samples under well defined conditions they can serve as an excellent model for the study of regulatory mechanisms of serum protein synthesis.", "contents": "[Blood protein synthesis in isolated liver cells]. Cells obtained by continuous perfusion with collagenase maintained their ultrastructure and their capacity for protein synthesis in contrast to mechanically isolated rat liver cells. Albumin and angiotensinogen (renin substrate) are synthesized and secreted and the synthesis of both proteins is stimulated by addition of hydrocortisone. As cell suspensions allow the simultaneous investigation of several samples under well defined conditions they can serve as an excellent model for the study of regulatory mechanisms of serum protein synthesis."}
{"id": "PMID:193771", "title": "Phosphofructokinase (isozymes) activation by theophylline or by 3',5' cyclic AMP administration.", "content": "Phosphofructokinase activity of rat thyroid, kidney and muscle can be enhanced by in vivo administration of theophylline or cyclic AMP. This enhancement occurs in the different tissues to a different extent depending on the tissue-specific isozymes. Thyroid and muscle phosphofructokinase which is mainly A-type, is strongly stimulated after administering theophylline in the drinking water over a 8 days period. The kidney enzyme which encompasses about 50% of each A and B type is activated to a lesser extent. Liver phosphofructokinase which is pure B-type shows very little response if any. Comparable results have been obtained with either the muscle or liver enzyme after two to four hours treatment with a single injection of 10 mg/rat of either cyclic AMP or theophylline. This short-term activation could be eliminated by treating the animals with Actinomycin D, 30 min prior to theophylline or cyclic AMP. The possible mechanisms leading to the enhancement of phosphofructokinase activity are discussed.", "contents": "Phosphofructokinase (isozymes) activation by theophylline or by 3',5' cyclic AMP administration. Phosphofructokinase activity of rat thyroid, kidney and muscle can be enhanced by in vivo administration of theophylline or cyclic AMP. This enhancement occurs in the different tissues to a different extent depending on the tissue-specific isozymes. Thyroid and muscle phosphofructokinase which is mainly A-type, is strongly stimulated after administering theophylline in the drinking water over a 8 days period. The kidney enzyme which encompasses about 50% of each A and B type is activated to a lesser extent. Liver phosphofructokinase which is pure B-type shows very little response if any. Comparable results have been obtained with either the muscle or liver enzyme after two to four hours treatment with a single injection of 10 mg/rat of either cyclic AMP or theophylline. This short-term activation could be eliminated by treating the animals with Actinomycin D, 30 min prior to theophylline or cyclic AMP. The possible mechanisms leading to the enhancement of phosphofructokinase activity are discussed."}
{"id": "PMID:193772", "title": "Chemical proof of lipid-protein interactions by crosslinking photosensitive lipids to apoproteins. Intermolecular cross-linkage between high-density apolipoprotein A-I and lecithins and sphingomyelins.", "content": "The molecular interactions and spatial arrangements of phospholipids and apoproteins of human high-density lipoprotein were studied by a chemical approach. Phosphatidylcholines and sphingomyelins substituted with fatty acyl residues of high specific radioactivity and labelled with the photosensitive azido group in specific positions were prepared by chemical synthesis. They were recombined with apolipoprotein A-I of human serum high density lipoprotein. The lipoprotein complexes containing either azido lecithins or azidosphingo-myelins were purified by agarose chromatography from excess lipids. The irradiation was performed under conditions which prohibit the interference with the apoprotein structure as proven by circular dichroism, fluorescence spectroscopy, immunodiffusion test and disc electrophoresis. Non-covalently bound lipid molecules were removed by Sephadex LH 20 chromatography. Mild alkaline treatment liberated radioactive fatty acids which were not directly linked to the polypeptide chain, but rather via neighbouring phospholipid molecules. The lipoprotein appeared as a single radioactive band in dodecylsulfate polyacrylamide gel electrophoresis as seen by radioscanning, which further proved the covalent linkage of the fatty acyl residues to the polypeptide chain. In the immunodiffusion test, there is no difference between covalently crosslinked phospholipid-apoLp A-I complex and the non-photolyticall treated complex. This is the first chemical proof of the spatial relationship of the hydrophobic side chains of the lipid and polypeptide chains in a lipoprotein complex.", "contents": "Chemical proof of lipid-protein interactions by crosslinking photosensitive lipids to apoproteins. Intermolecular cross-linkage between high-density apolipoprotein A-I and lecithins and sphingomyelins. The molecular interactions and spatial arrangements of phospholipids and apoproteins of human high-density lipoprotein were studied by a chemical approach. Phosphatidylcholines and sphingomyelins substituted with fatty acyl residues of high specific radioactivity and labelled with the photosensitive azido group in specific positions were prepared by chemical synthesis. They were recombined with apolipoprotein A-I of human serum high density lipoprotein. The lipoprotein complexes containing either azido lecithins or azidosphingo-myelins were purified by agarose chromatography from excess lipids. The irradiation was performed under conditions which prohibit the interference with the apoprotein structure as proven by circular dichroism, fluorescence spectroscopy, immunodiffusion test and disc electrophoresis. Non-covalently bound lipid molecules were removed by Sephadex LH 20 chromatography. Mild alkaline treatment liberated radioactive fatty acids which were not directly linked to the polypeptide chain, but rather via neighbouring phospholipid molecules. The lipoprotein appeared as a single radioactive band in dodecylsulfate polyacrylamide gel electrophoresis as seen by radioscanning, which further proved the covalent linkage of the fatty acyl residues to the polypeptide chain. In the immunodiffusion test, there is no difference between covalently crosslinked phospholipid-apoLp A-I complex and the non-photolyticall treated complex. This is the first chemical proof of the spatial relationship of the hydrophobic side chains of the lipid and polypeptide chains in a lipoprotein complex."}
{"id": "PMID:193773", "title": "Shutoff of histone synthesis by Mengovirus infection of Ehrlich ascites tumor cells.", "content": "The histone synthesizing capacity of mengovirus-infected Ehrlich ascites tumor cells and of their corresponding postnuclear supernatants was investigated as a funcion of time post-infection. In addition, histone synthesis was compared with the synthesis of other basic host proteins under identical conditions. In the scope of mengovirus infection of Ehrlich ascites tumor cells the less complex fraction comprising basic protein, separated from the acidic proteins by carboxymethyl cellulose chromatography, can be regarded as a representative of total host protein. Histones and the remaining basic host proteins therefore are well suited as easily identifiable indicators of the host protein synthesizing potential of mengovirus-infected Ehrlich ascites tumor cells. The cessation of histone synthesis proceeds faster than the arrest of the synthesis of other basic host protein.", "contents": "Shutoff of histone synthesis by Mengovirus infection of Ehrlich ascites tumor cells. The histone synthesizing capacity of mengovirus-infected Ehrlich ascites tumor cells and of their corresponding postnuclear supernatants was investigated as a funcion of time post-infection. In addition, histone synthesis was compared with the synthesis of other basic host proteins under identical conditions. In the scope of mengovirus infection of Ehrlich ascites tumor cells the less complex fraction comprising basic protein, separated from the acidic proteins by carboxymethyl cellulose chromatography, can be regarded as a representative of total host protein. Histones and the remaining basic host proteins therefore are well suited as easily identifiable indicators of the host protein synthesizing potential of mengovirus-infected Ehrlich ascites tumor cells. The cessation of histone synthesis proceeds faster than the arrest of the synthesis of other basic host protein."}
{"id": "PMID:193774", "title": "[A rheological study on plasma lipoproteins (author's transl)].", "content": "Lipoproteins of the types LpB and LP-X are studied in a microviscometer to measure intrinsic viscosity. Up to a shear rate of 1700s-1 no shear dependence of viscosity is observed. Intrinsic viscosities are 3.5 and 4.0 for LpB, and 8.5 ml/g for LP-X. Density measurements are used to calculate apparent specific volumes. The results are compatible with a spherical model. An upper limit of 0.45 is estimated for the hydration.", "contents": "[A rheological study on plasma lipoproteins (author's transl)]. Lipoproteins of the types LpB and LP-X are studied in a microviscometer to measure intrinsic viscosity. Up to a shear rate of 1700s-1 no shear dependence of viscosity is observed. Intrinsic viscosities are 3.5 and 4.0 for LpB, and 8.5 ml/g for LP-X. Density measurements are used to calculate apparent specific volumes. The results are compatible with a spherical model. An upper limit of 0.45 is estimated for the hydration."}
{"id": "PMID:193780", "title": "Characterization of immunoglobulins eluted from hamster SV40 tumors.", "content": "In order to determine if progressively growing tumors specifically bind antitumor antibody, which might play a role in blocking tumor specific cell-mediated immunity, low pH elutions were performed on autochthonous and transplantable SV40 tumors growing in situ for various lengths of time. Ouchterlony analysis revealed that IgG2 was present in all tumor eluates, while IgG1 was present only in eluates from tumors that grew in situ for more than sixty days. IgA and IgM were also found in most eluates but their presence did not correlate with duration of in situ growth. While no antibody to cell surface antigens could be detected, the eluates did possess antibody activity directed to the SV40 nuclear T-antigen. The tumor eluates did not block in vitro lymphocyte dependent microcytotoxicity of immune lymphocytes against cultured SV40 tumor cells. The biological role and significance of different classes of immunoglobulins bound to the surface of growing tumor cells is still poorly understood and requires further study.", "contents": "Characterization of immunoglobulins eluted from hamster SV40 tumors. In order to determine if progressively growing tumors specifically bind antitumor antibody, which might play a role in blocking tumor specific cell-mediated immunity, low pH elutions were performed on autochthonous and transplantable SV40 tumors growing in situ for various lengths of time. Ouchterlony analysis revealed that IgG2 was present in all tumor eluates, while IgG1 was present only in eluates from tumors that grew in situ for more than sixty days. IgA and IgM were also found in most eluates but their presence did not correlate with duration of in situ growth. While no antibody to cell surface antigens could be detected, the eluates did possess antibody activity directed to the SV40 nuclear T-antigen. The tumor eluates did not block in vitro lymphocyte dependent microcytotoxicity of immune lymphocytes against cultured SV40 tumor cells. The biological role and significance of different classes of immunoglobulins bound to the surface of growing tumor cells is still poorly understood and requires further study."}
{"id": "PMID:193786", "title": "Variation between strains of hamsters in the lethality of Pichinde virus infections.", "content": "Infection by Pichinde virus, a member of the arenavirus group, was studied in Golden Syrian hamsters (Mesocricetus auratus) with regard to possible mechanisms of resistance to virus infection in adult hamsters. Two hamster strains were found to differ in their susceptibility to lethal Pichinde virus infection. LVG/Lak randomly bred hamsters were found to be 100% susceptible to low doses of Pichinde virus during the first 6 days of life, but after 8 days of life, mortality was uncommon. Peak virus titers in the serum of animals infected at 3 days of life were 4 logs greater than in animals infected at 12 days. MHA/Lak inbred hamsters, in contrast, were found to be susceptible to lethal virus infection both as newborns and as adults. Peak virus titers of greater than 10(8) plaque-forming units/ml were observed in serum 8 days after infection of adult MHA hamsters as compared with less than 10(3) plaque-forming units/ml in the serum of adult LVG hamsters. Cultured primary kidney cells and peritoneal macrophages from either hamster strain supported Pichinde virus replication equally well in vitro. Antibodies to the complement-fixing antigens and to antigens at the surface of virus-infected cells were produced by both strains of hamsters. Cyclophosphamide immunosuppression rendered adult LVG animals susceptible to lethal infections, and virus grew to high titers in the treated animals. These findings suggest that immunological factors that appear early in life in LVG hamsters and are deficient in MHA hamsters limit Pichinde virus infection. Unlike previously reported arenavirus diseases, the observations suggest that death is produced by a direct viral effect and not through immunopathological mechanisms.", "contents": "Variation between strains of hamsters in the lethality of Pichinde virus infections. Infection by Pichinde virus, a member of the arenavirus group, was studied in Golden Syrian hamsters (Mesocricetus auratus) with regard to possible mechanisms of resistance to virus infection in adult hamsters. Two hamster strains were found to differ in their susceptibility to lethal Pichinde virus infection. LVG/Lak randomly bred hamsters were found to be 100% susceptible to low doses of Pichinde virus during the first 6 days of life, but after 8 days of life, mortality was uncommon. Peak virus titers in the serum of animals infected at 3 days of life were 4 logs greater than in animals infected at 12 days. MHA/Lak inbred hamsters, in contrast, were found to be susceptible to lethal virus infection both as newborns and as adults. Peak virus titers of greater than 10(8) plaque-forming units/ml were observed in serum 8 days after infection of adult MHA hamsters as compared with less than 10(3) plaque-forming units/ml in the serum of adult LVG hamsters. Cultured primary kidney cells and peritoneal macrophages from either hamster strain supported Pichinde virus replication equally well in vitro. Antibodies to the complement-fixing antigens and to antigens at the surface of virus-infected cells were produced by both strains of hamsters. Cyclophosphamide immunosuppression rendered adult LVG animals susceptible to lethal infections, and virus grew to high titers in the treated animals. These findings suggest that immunological factors that appear early in life in LVG hamsters and are deficient in MHA hamsters limit Pichinde virus infection. Unlike previously reported arenavirus diseases, the observations suggest that death is produced by a direct viral effect and not through immunopathological mechanisms."}
{"id": "PMID:193787", "title": "Polymyxins as inhibitors of polyclonal B-cell activators in murine lymphocyte cultures.", "content": "The polymyxin antibiotics polymyxin B sulfate and colistin methane sulfonate were examined for their ability to inhibit responses to the polyclonal B-cell activators (PBA) bacterial lipopolysaccharide (LPS), dextran sulfate (DS), pneumococcal polysaccharide (SIII), and purified protein derivative of tuberculin (PPD) in spleen cell cultures. Polymyxin concentrations of 1 and 10 microng/ml significantly inhibited both the deoxyribonucleic acid synthetic and polyclonal antibody responses stimulated by LPS, DS, and SIII. At these concentrations of polymyxins, responses to PPD and to the T-cell mitogens concanavalin A and phytohemagglutinin were not affected. Inhibition was not caused by a generalized lymphocyte toxicity. After dialysis of LPS-polymyxin and DS-polymyxin mixtures, the PBA preparations showed decreased mitogenic activity. Thus, the polymyxins probably interacted directly with the LPS and DS molecules. The mitogenic response to DS was more significantly inhibited than the response to a nonsulfated dextran. The cationic property of the polymyxins probably allows attachment to negatively charged groups in the mitogenically relevant parts of some but not all PBA molecules,, this attachment resulting in the loss of PBA activity.", "contents": "Polymyxins as inhibitors of polyclonal B-cell activators in murine lymphocyte cultures. The polymyxin antibiotics polymyxin B sulfate and colistin methane sulfonate were examined for their ability to inhibit responses to the polyclonal B-cell activators (PBA) bacterial lipopolysaccharide (LPS), dextran sulfate (DS), pneumococcal polysaccharide (SIII), and purified protein derivative of tuberculin (PPD) in spleen cell cultures. Polymyxin concentrations of 1 and 10 microng/ml significantly inhibited both the deoxyribonucleic acid synthetic and polyclonal antibody responses stimulated by LPS, DS, and SIII. At these concentrations of polymyxins, responses to PPD and to the T-cell mitogens concanavalin A and phytohemagglutinin were not affected. Inhibition was not caused by a generalized lymphocyte toxicity. After dialysis of LPS-polymyxin and DS-polymyxin mixtures, the PBA preparations showed decreased mitogenic activity. Thus, the polymyxins probably interacted directly with the LPS and DS molecules. The mitogenic response to DS was more significantly inhibited than the response to a nonsulfated dextran. The cationic property of the polymyxins probably allows attachment to negatively charged groups in the mitogenically relevant parts of some but not all PBA molecules,, this attachment resulting in the loss of PBA activity."}
{"id": "PMID:193788", "title": "Characterization of antigens from type A and B yeast cells of Histoplasma capsulatum.", "content": "The antigenic composition of cytoplasmic extract and culture filtrate antigens of type A and B yeast cells of Histoplasma capsulatum grown in a synthetic medium was studied. These preparations from type A and B yeast cells contained varying amounts of protein, carbohydrates, and protein-carbohydrate complexes. The antigenic analysis of these preparations was performed by antigen-antiserum absorption with subsequent immunodiffusion and cross-immunoelectrophoresis with absorption in situ in an intermediate gel. All protein antigens observed in culture filtrate of either type A or B yeast cells were also present in the cytoplasmic extracts of the same type. The cytoplasmic extract of type A and B yeast cells each contained certain characteristic antigens that were not shared by the other type. Rocket immunoelectrophoresis with different molecular weight fractions of the antigenic preparations from both types indicated the polydisperse nature of Histoplasma yeast cell antigens.", "contents": "Characterization of antigens from type A and B yeast cells of Histoplasma capsulatum. The antigenic composition of cytoplasmic extract and culture filtrate antigens of type A and B yeast cells of Histoplasma capsulatum grown in a synthetic medium was studied. These preparations from type A and B yeast cells contained varying amounts of protein, carbohydrates, and protein-carbohydrate complexes. The antigenic analysis of these preparations was performed by antigen-antiserum absorption with subsequent immunodiffusion and cross-immunoelectrophoresis with absorption in situ in an intermediate gel. All protein antigens observed in culture filtrate of either type A or B yeast cells were also present in the cytoplasmic extracts of the same type. The cytoplasmic extract of type A and B yeast cells each contained certain characteristic antigens that were not shared by the other type. Rocket immunoelectrophoresis with different molecular weight fractions of the antigenic preparations from both types indicated the polydisperse nature of Histoplasma yeast cell antigens."}
{"id": "PMID:193789", "title": "Human nasal epithelial cell culture system: evaluation of response to human interferons.", "content": "This report describes the response of human nasal epithelial cells to exogenously applied human interferon (IF). To measure the response, a system developed to study human nasal epithelial cells in vitro was used. Nasal epithelial cells responded equally to both leukocyte and fibroblast IF, with development of resistance to virus replication that was time and dose dependent. Cells required contact with 1,000 U of IF (400 69/19 reference units) for 4 h to produce consistently a significant reduction in virus yield. This in vitro cell cultured system may be useful in predicting the in vivo response of human IF in respiratory viral infections.", "contents": "Human nasal epithelial cell culture system: evaluation of response to human interferons. This report describes the response of human nasal epithelial cells to exogenously applied human interferon (IF). To measure the response, a system developed to study human nasal epithelial cells in vitro was used. Nasal epithelial cells responded equally to both leukocyte and fibroblast IF, with development of resistance to virus replication that was time and dose dependent. Cells required contact with 1,000 U of IF (400 69/19 reference units) for 4 h to produce consistently a significant reduction in virus yield. This in vitro cell cultured system may be useful in predicting the in vivo response of human IF in respiratory viral infections."}
{"id": "PMID:193790", "title": "Biochemical and immunological characterization of deoxythymidine kinase of thymidine kinaseless HeLa cells biochemically transformed by herpes simplex virus type.", "content": "Thymidine kinase (TK) from herpes simplex virus type 1 (HSV-1) biochemically transformed HeLa cells, purified by affinity chromatography, has been characterized with respect to its electrophoretic mobility, molecular weight, activation energy, substrate specificity, and immunological specificity. TK purified from HSV-1-transformed HeLa cells has the same electrophoretic mobility as TK purified from HeLa cells lytically infected with HSV-1. The sedimentation velocity of purified TK from transformed cells was similar to that previously reported for the lytic enzyme, and its molecular weight was estimated to be 70,000. The activation energy of purified transformed-cell TK was 18.3 kcal/mol. Antiserum prepared against purified HSV-1 TK, although it showed some cross-reactivity, preferentially neutralized homologous TK. The transformed-cell TK antiserum also neutralized the deoxycytidine kinase activity of HSV-1-infected cell extracts but had no effect on deoxycytidine kinase activity of HSV-2-infected cell extract. These results further support the notion that TK acquired by HeLa cells transformed by HSV-1 is of viral and not of cellular origin.", "contents": "Biochemical and immunological characterization of deoxythymidine kinase of thymidine kinaseless HeLa cells biochemically transformed by herpes simplex virus type. Thymidine kinase (TK) from herpes simplex virus type 1 (HSV-1) biochemically transformed HeLa cells, purified by affinity chromatography, has been characterized with respect to its electrophoretic mobility, molecular weight, activation energy, substrate specificity, and immunological specificity. TK purified from HSV-1-transformed HeLa cells has the same electrophoretic mobility as TK purified from HeLa cells lytically infected with HSV-1. The sedimentation velocity of purified TK from transformed cells was similar to that previously reported for the lytic enzyme, and its molecular weight was estimated to be 70,000. The activation energy of purified transformed-cell TK was 18.3 kcal/mol. Antiserum prepared against purified HSV-1 TK, although it showed some cross-reactivity, preferentially neutralized homologous TK. The transformed-cell TK antiserum also neutralized the deoxycytidine kinase activity of HSV-1-infected cell extracts but had no effect on deoxycytidine kinase activity of HSV-2-infected cell extract. These results further support the notion that TK acquired by HeLa cells transformed by HSV-1 is of viral and not of cellular origin."}
{"id": "PMID:193791", "title": "Indirect fluorescent-antibody test for human cytomegalovirus infection in the absence of interfering immunoglobulin G receptors.", "content": "The presence of immunoglobulin G receptors in human fibroblasts infected with human cytomegalovirus (CMV) resulted in a nonspecific cytoplasmic reaction in the indirect fluorescent-antibody test. Both CMV antibody-positive and antibody-negative sera from human or other animal species produced the cytoplasmic reaction. The substitution of a simian CMV strain for the human virus successfully eliminated this cytoplasmic reaction and, thus, allowed for the observation of virus-induced fluorescent intranuclear inclusions. With the latter system, CMV antibody titers in human sera were equivalent to those obtained by using the human virus and, in addition, allowed for the detection of relatively low-titered serum samples in which antibody measurement was difficult when human CMV-infected cells were used in the indirect fluorescent-antibody test.", "contents": "Indirect fluorescent-antibody test for human cytomegalovirus infection in the absence of interfering immunoglobulin G receptors. The presence of immunoglobulin G receptors in human fibroblasts infected with human cytomegalovirus (CMV) resulted in a nonspecific cytoplasmic reaction in the indirect fluorescent-antibody test. Both CMV antibody-positive and antibody-negative sera from human or other animal species produced the cytoplasmic reaction. The substitution of a simian CMV strain for the human virus successfully eliminated this cytoplasmic reaction and, thus, allowed for the observation of virus-induced fluorescent intranuclear inclusions. With the latter system, CMV antibody titers in human sera were equivalent to those obtained by using the human virus and, in addition, allowed for the detection of relatively low-titered serum samples in which antibody measurement was difficult when human CMV-infected cells were used in the indirect fluorescent-antibody test."}
{"id": "PMID:193792", "title": "Antibody-dependent cellular protection against herpes simplex virus dissemination as revealed by viral plauqe and infectivity assays.", "content": "Mouse nonimmune peripheral blood lymphocytes (PBL) plus antibody to herpes simplex virus inhibited virus dissemination in herpes simplex virus-infected 3T3 cell culture as revealed by development of viral plaque, size of immunofluorescent foci, appearance of polycaryocytes, and viral infectivity appearing in the culture. These nonimmune PBL did not act alone in inibiting virus dissemination, but did act synergistically in combination with antibody. The ratio of PBL to target monolayer cells needed to produce this effect was 20. Splenic lymphocytes had weak activity, whereas thymocytes were without effect, even in the presence of antibody. Neither interferon nor lymphotoxin was detected in this lymphocyte-mediated response. These findings support previous observations, based on cytotoxicity assays, that antibody-dependent cellular immune processes could be important in control of and recovery from herpesvirus infection.", "contents": "Antibody-dependent cellular protection against herpes simplex virus dissemination as revealed by viral plauqe and infectivity assays. Mouse nonimmune peripheral blood lymphocytes (PBL) plus antibody to herpes simplex virus inhibited virus dissemination in herpes simplex virus-infected 3T3 cell culture as revealed by development of viral plaque, size of immunofluorescent foci, appearance of polycaryocytes, and viral infectivity appearing in the culture. These nonimmune PBL did not act alone in inibiting virus dissemination, but did act synergistically in combination with antibody. The ratio of PBL to target monolayer cells needed to produce this effect was 20. Splenic lymphocytes had weak activity, whereas thymocytes were without effect, even in the presence of antibody. Neither interferon nor lymphotoxin was detected in this lymphocyte-mediated response. These findings support previous observations, based on cytotoxicity assays, that antibody-dependent cellular immune processes could be important in control of and recovery from herpesvirus infection."}
{"id": "PMID:193793", "title": "Direct serological assay for the heat-labile enterotoxin of Escherichia coli, using passive immune hemolysis.", "content": "Sheep erythrocytes sensitized with the heat-labile enterotoxin (LT) of Escherichia coli exhibited passive immune hemolysis (PIH) when exposed to specific antitoxin and complement. Thus, PIH serves as the basis for an in vitro serological assay for LT that is sufficiently specific and sensitive to differentiate  LT-positive and LT-negative E. coli isolates. The PIH assay for E. coli LT has been performed with the standard Microtiter system and also by a tube method employing the spectrophotometric determination of hemoglobin release. The spectrophotometric method enhances the sensitivity, accuracy, and objectivity of the PIH assay. The increased sensitivity of the spectrophotometric method also facilitates the identification of LT-positive cultures employing polymyxin \"mini-extracts\" of whole overnight (18 h) broth cultures of 2.0% Casamino Acid-0.6% yeast extract-salts medium rather than mini-extracts of cells derived from 3.5-h subcultures. Thus, large numbers of E. coli isolates can be individually tested for LT in less than 24 h after broth inoculation by a rapid in vitro assay which requires anti-LT serum as the only specific reagent.", "contents": "Direct serological assay for the heat-labile enterotoxin of Escherichia coli, using passive immune hemolysis. Sheep erythrocytes sensitized with the heat-labile enterotoxin (LT) of Escherichia coli exhibited passive immune hemolysis (PIH) when exposed to specific antitoxin and complement. Thus, PIH serves as the basis for an in vitro serological assay for LT that is sufficiently specific and sensitive to differentiate  LT-positive and LT-negative E. coli isolates. The PIH assay for E. coli LT has been performed with the standard Microtiter system and also by a tube method employing the spectrophotometric determination of hemoglobin release. The spectrophotometric method enhances the sensitivity, accuracy, and objectivity of the PIH assay. The increased sensitivity of the spectrophotometric method also facilitates the identification of LT-positive cultures employing polymyxin \"mini-extracts\" of whole overnight (18 h) broth cultures of 2.0% Casamino Acid-0.6% yeast extract-salts medium rather than mini-extracts of cells derived from 3.5-h subcultures. Thus, large numbers of E. coli isolates can be individually tested for LT in less than 24 h after broth inoculation by a rapid in vitro assay which requires anti-LT serum as the only specific reagent."}
{"id": "PMID:193794", "title": "Regulation of staphylococcal enterotoxin B.", "content": "The effect of glucose and the glucose analogues 2-deoxyglucose and alpha-methyl-glucoside on the synthesis and regulation of staphylococcal enterotoxin B was examined. The attenuating effect of glucose on staphylococcal enterotoxin B synthesis was observed. However, when this effect was examined with analogues of glucose, contradictory responses were seen. alpha-Methylglucoside had a slight stimulatory effect on enterotoxin production and other extracellular proteins, whereas 2-deoxyglucose markedly inhibited enterotoxin production. beta-hemolysin and staphylococcal nuclease were also inhibited by 2-deoxy glucose but the synthesis of nuclease could be rescued by the addition of glucose to 2-deoxyglucose-containing cultures. Enterotoxin and beta-hemolysin synthesis were not subject to glucose rescue. The cells used in this study were permeable to cyclic 3',5'-adenosine monophosphate, but the addition of this compound did not reverse glucose repression or 2-deoxyglucose inhibition of enterotoxin B synthesis. We conclude from these data that the regulation of enterotoxin is not under catabolite control as previously reported.", "contents": "Regulation of staphylococcal enterotoxin B. The effect of glucose and the glucose analogues 2-deoxyglucose and alpha-methyl-glucoside on the synthesis and regulation of staphylococcal enterotoxin B was examined. The attenuating effect of glucose on staphylococcal enterotoxin B synthesis was observed. However, when this effect was examined with analogues of glucose, contradictory responses were seen. alpha-Methylglucoside had a slight stimulatory effect on enterotoxin production and other extracellular proteins, whereas 2-deoxyglucose markedly inhibited enterotoxin production. beta-hemolysin and staphylococcal nuclease were also inhibited by 2-deoxy glucose but the synthesis of nuclease could be rescued by the addition of glucose to 2-deoxyglucose-containing cultures. Enterotoxin and beta-hemolysin synthesis were not subject to glucose rescue. The cells used in this study were permeable to cyclic 3',5'-adenosine monophosphate, but the addition of this compound did not reverse glucose repression or 2-deoxyglucose inhibition of enterotoxin B synthesis. We conclude from these data that the regulation of enterotoxin is not under catabolite control as previously reported."}
{"id": "PMID:193795", "title": "Thymidine kinaseless revertants of Ltk- cells transformed by herpes simplex virus type 1 are resistant to retransformation by homologous virus.", "content": "Mouse L cells lacking thymidine kinase (Ltk-) that had been transformed to the thymidine kinase-positive (tk+) phenotype by herpes simplex virus type 1 (HSV-1) were cultured in medium containing tritiated thymidine. Six clonal lines of cells surviving this treatment were found to have the following properties: (i) the cells were tk- and had spontaneous back-reversion frequencies to the tk+ phenotype of 10(-5) or less, (ii) the cells contained HSV antigens, although in lesser amounts than in the parental transformed cells, and (iii) the cells were retransformable to the tk+ phenotype by HSV-1 at frequencies of about 1 to 13% of the frequency of the primary transformation of LtK- cells. HSV-1 plaqued as efficiently on monolayers of these cells and replicated in them to the same extent as it did in Ltk- cells. These results indicate that HSV-1-transformed L cells surviving selection with tritiated thymidine are unlike the parental Ltk- cells in that they are damaged in such a way that the cells are resistant to retransformation by homologous virus, although they remain fully permissive for virus replication.", "contents": "Thymidine kinaseless revertants of Ltk- cells transformed by herpes simplex virus type 1 are resistant to retransformation by homologous virus. Mouse L cells lacking thymidine kinase (Ltk-) that had been transformed to the thymidine kinase-positive (tk+) phenotype by herpes simplex virus type 1 (HSV-1) were cultured in medium containing tritiated thymidine. Six clonal lines of cells surviving this treatment were found to have the following properties: (i) the cells were tk- and had spontaneous back-reversion frequencies to the tk+ phenotype of 10(-5) or less, (ii) the cells contained HSV antigens, although in lesser amounts than in the parental transformed cells, and (iii) the cells were retransformable to the tk+ phenotype by HSV-1 at frequencies of about 1 to 13% of the frequency of the primary transformation of LtK- cells. HSV-1 plaqued as efficiently on monolayers of these cells and replicated in them to the same extent as it did in Ltk- cells. These results indicate that HSV-1-transformed L cells surviving selection with tritiated thymidine are unlike the parental Ltk- cells in that they are damaged in such a way that the cells are resistant to retransformation by homologous virus, although they remain fully permissive for virus replication."}
{"id": "PMID:193796", "title": "Adenovirus of ring-necked pheasants: purification and partial characterization of marble spleen disease virus.", "content": "A method for purification of marble spleen disease virus (MSDV) from the spleens of infected turkeys and pheasants is described. It combines chloroform or fluorocarbon extraction with subsequent purification by centrifugation on a cushion of cesium chloride (CsCl). Further purification of MSDV was accomplished with a CsCl equilibrium density gradient. A viral buoyant density of approximately 1.32 to 1.33 g/cm3 was determined. Negative-stain electron microscopy revealed that virus isopycnically banded by CsCl gradient had non-enveloped icosahedral capsids composed of 252 capsomeres. The direct colorimetric diphenylamine assay indicated that MSDV has deoxyribonucleic acid as its nucleic acid. The above evidence demonstrates that MSDV is an avian adenovirus, the first recognized in the ring-necked pheasant (Phasianus colchicus L.).", "contents": "Adenovirus of ring-necked pheasants: purification and partial characterization of marble spleen disease virus. A method for purification of marble spleen disease virus (MSDV) from the spleens of infected turkeys and pheasants is described. It combines chloroform or fluorocarbon extraction with subsequent purification by centrifugation on a cushion of cesium chloride (CsCl). Further purification of MSDV was accomplished with a CsCl equilibrium density gradient. A viral buoyant density of approximately 1.32 to 1.33 g/cm3 was determined. Negative-stain electron microscopy revealed that virus isopycnically banded by CsCl gradient had non-enveloped icosahedral capsids composed of 252 capsomeres. The direct colorimetric diphenylamine assay indicated that MSDV has deoxyribonucleic acid as its nucleic acid. The above evidence demonstrates that MSDV is an avian adenovirus, the first recognized in the ring-necked pheasant (Phasianus colchicus L.)."}
{"id": "PMID:193797", "title": "Affinity of Sendai virus for the inner ear of mice.", "content": "The direct immunofluorescent antibody method revealed that Sendai virus, which was thought to be most prevalent in respiratory diseases in mice, infected the inner ear of mice when the virus was injected intracerebrally. Specific immunofluorescence that indicated the presence of antigens of Sendai virus was observed in both perilymphatic and endolymphatic structures. The routes of virus spread are discussed. This experimental study, using newborn mice and Sendai virus, may be useful for the investigation of the pathogenesis of viral labyrinthitis not only because of the high frequency of inner ear infection, but also because of long-time survivors which facilitate prolonged observation.", "contents": "Affinity of Sendai virus for the inner ear of mice. The direct immunofluorescent antibody method revealed that Sendai virus, which was thought to be most prevalent in respiratory diseases in mice, infected the inner ear of mice when the virus was injected intracerebrally. Specific immunofluorescence that indicated the presence of antigens of Sendai virus was observed in both perilymphatic and endolymphatic structures. The routes of virus spread are discussed. This experimental study, using newborn mice and Sendai virus, may be useful for the investigation of the pathogenesis of viral labyrinthitis not only because of the high frequency of inner ear infection, but also because of long-time survivors which facilitate prolonged observation."}
{"id": "PMID:193798", "title": "Efficacy of herpes simplex virus type 1 immunization in protecting against acute and latent infection by herpes simplex virus type 2 in mice.", "content": "ICR mice were immunized with herpes simplex virus type 1 (HSV-1) and later challenged with HSV-2 by footpad inoculation. Both immunized animals and age-matched, nonimmunized controls were observed for ascending neurological disease and latent infection of spinal ganglia resulting from the HSV-2 challenge. Control animals had a 78% incidence of acute and latent infection compared with a 1.7% incidence in immunized mice. The data show immunity to HSV-1 is protective against both acute and latent infection by HSV-2.", "contents": "Efficacy of herpes simplex virus type 1 immunization in protecting against acute and latent infection by herpes simplex virus type 2 in mice. ICR mice were immunized with herpes simplex virus type 1 (HSV-1) and later challenged with HSV-2 by footpad inoculation. Both immunized animals and age-matched, nonimmunized controls were observed for ascending neurological disease and latent infection of spinal ganglia resulting from the HSV-2 challenge. Control animals had a 78% incidence of acute and latent infection compared with a 1.7% incidence in immunized mice. The data show immunity to HSV-1 is protective against both acute and latent infection by HSV-2."}
{"id": "PMID:193799", "title": "Effects of Bordetella pertussis on the sensitivity of inbred mice to vasoactive amines.", "content": "Pretreatment with Bordetella pertussis was determined to increase significantly the hypovolemia induced by intravenous injections of histamine either alone or in mixture with serotonin in a total of 26 different strains of mice. Two factors affecting the mortality rates observed by challenge after B. pertussis treatment were: the sensitivity of the strains to vasoactive amines before B. pertussis treatment, and their resistance to acute hypovolemic shock. Appropriate crosses and backcrosses between resistant and susceptible strains failed to demonstrate a clear pattern of inheritance of the susceptibility to B. pertussis effects.", "contents": "Effects of Bordetella pertussis on the sensitivity of inbred mice to vasoactive amines. Pretreatment with Bordetella pertussis was determined to increase significantly the hypovolemia induced by intravenous injections of histamine either alone or in mixture with serotonin in a total of 26 different strains of mice. Two factors affecting the mortality rates observed by challenge after B. pertussis treatment were: the sensitivity of the strains to vasoactive amines before B. pertussis treatment, and their resistance to acute hypovolemic shock. Appropriate crosses and backcrosses between resistant and susceptible strains failed to demonstrate a clear pattern of inheritance of the susceptibility to B. pertussis effects."}
{"id": "PMID:193800", "title": "Histopathological changes in mice treated with extracts of the histamine-sensitizing factor of Bordetella pertussis.", "content": "The histamine-sensitizing factor (HSF) of Bordetella pertussis was isolated in a highly purified form. In addition to inducing profound sensitization to histamine, it also caused a significant lymphocytosis and produced an enhancement of reaginic antibody production in animals upon immunization with antigen. Biologically active doses of HSF produced significant pathological changes in mice including congestion and edema of the lung and a marked depletion of cells in the thymus, white pulp of the spleen, and lymph nodes. The lymphocytosis and histological changes in the lungs and lymphoid organs were observed in different strains of mice injected with HSF (even those that are resistant to its histamine-sensitizing effects). Heating HSF at 80 degrees C for 30 min, a treatment that destroys histamine sensitizing and lymphocytosis promoting activities, completely abolishes the ability to induce the changes observed in the lungs and lymphoid organs.", "contents": "Histopathological changes in mice treated with extracts of the histamine-sensitizing factor of Bordetella pertussis. The histamine-sensitizing factor (HSF) of Bordetella pertussis was isolated in a highly purified form. In addition to inducing profound sensitization to histamine, it also caused a significant lymphocytosis and produced an enhancement of reaginic antibody production in animals upon immunization with antigen. Biologically active doses of HSF produced significant pathological changes in mice including congestion and edema of the lung and a marked depletion of cells in the thymus, white pulp of the spleen, and lymph nodes. The lymphocytosis and histological changes in the lungs and lymphoid organs were observed in different strains of mice injected with HSF (even those that are resistant to its histamine-sensitizing effects). Heating HSF at 80 degrees C for 30 min, a treatment that destroys histamine sensitizing and lymphocytosis promoting activities, completely abolishes the ability to induce the changes observed in the lungs and lymphoid organs."}
{"id": "PMID:193801", "title": "Neutralizing EBV-specific IgA in throat washings of nasopharyngeal carcinoma (NPC) patients.", "content": "Throat washings from 26 nasopharyngeal carcinoma (NPC) patients from Hong Kong and Tunisia were studied for the presence of transforming EBV. Only six (23%) were found positive which led to the hypothesis of a neutralizing factor in such salivas. The search for EBV-specific antibodies showed that NPC saliva contained neutralizing VCA and EA IgA (54 and 27% respectively) and VCA and EA IgG (73 AND 54% respectively). Both transforming and non-transforming throat washings contained virus particles as visualized by electron microscopy, but in non-transforming salivas (containing IgA and IgG) the particles were found to be clumped. Comparative study of throat washings from patients with Burkitt's lymphoma (BL); infectious mononucleosis (IM), immunodeficiencies, other cancers, and healthy subjects showed that IgA were restricted to NPC cases.", "contents": "Neutralizing EBV-specific IgA in throat washings of nasopharyngeal carcinoma (NPC) patients. Throat washings from 26 nasopharyngeal carcinoma (NPC) patients from Hong Kong and Tunisia were studied for the presence of transforming EBV. Only six (23%) were found positive which led to the hypothesis of a neutralizing factor in such salivas. The search for EBV-specific antibodies showed that NPC saliva contained neutralizing VCA and EA IgA (54 and 27% respectively) and VCA and EA IgG (73 AND 54% respectively). Both transforming and non-transforming throat washings contained virus particles as visualized by electron microscopy, but in non-transforming salivas (containing IgA and IgG) the particles were found to be clumped. Comparative study of throat washings from patients with Burkitt's lymphoma (BL); infectious mononucleosis (IM), immunodeficiencies, other cancers, and healthy subjects showed that IgA were restricted to NPC cases."}
{"id": "PMID:193802", "title": "Immune response of athymic nude mice to papovavirus SV40 tumor-associated antigens.", "content": "The requirement of T cell functions in the induction of immune response to SV40-specific transplantation rejection antigen and intranuclear tumor antigen was studied using athymic nude mice. The results obtained indicate that virus-immunized athymic nude mice were unable to reject SV40 tumor cell challenge, and sensitized lymphocytes capable of inhibiting tumor growth in vivo could not be demonstrated in the spleens of virus-immunized mice. Athymic nude mice bearing tumor induced by virus-free SV40-transformed BALB/c cells failed to develop antibodies to intranuclear T antigen. Athymic nude mice also failed to respond to viral antigens. Thus it can be concluded that T cell functions are required in the induction of cellular immune response to SV40-specific transplantation rejection antigen and in humoral immune response to SV40-specific T antigen and virion antigen.", "contents": "Immune response of athymic nude mice to papovavirus SV40 tumor-associated antigens. The requirement of T cell functions in the induction of immune response to SV40-specific transplantation rejection antigen and intranuclear tumor antigen was studied using athymic nude mice. The results obtained indicate that virus-immunized athymic nude mice were unable to reject SV40 tumor cell challenge, and sensitized lymphocytes capable of inhibiting tumor growth in vivo could not be demonstrated in the spleens of virus-immunized mice. Athymic nude mice bearing tumor induced by virus-free SV40-transformed BALB/c cells failed to develop antibodies to intranuclear T antigen. Athymic nude mice also failed to respond to viral antigens. Thus it can be concluded that T cell functions are required in the induction of cellular immune response to SV40-specific transplantation rejection antigen and in humoral immune response to SV40-specific T antigen and virion antigen."}
{"id": "PMID:193804", "title": "Hepatography and liver lymphography by retrograde biliary ethiodol infusion: an experimental study in the dog.", "content": "Ethiodol in dosages of 0.5-3 ml/kg was retrogradely infused with hydrostatic pressure of 50--100 cm water into the biliary system of nine cholecystectomized dogs equipped with a Thomas cannula in the second portion of the duodenum, allowing cannulation of the common bile duct with a Foley catheter under direct vision. A total of 18 examinations were performed. A dense hepatogram and complete visualization of the hepatic lymph nodes were obtained when the infused Ethiodol dosage exceeded the capacity of the biliary system by 10 ml or more. The hepatogram lasted for three to four months and the lymph nodes were opacified for a year and longer. Contrary to angiographic contrast agents, Ethiodol retrogradely infused into the biliary system primarily refluxes from the biliary system to the lymph and not to the blood. Judged by serial chest radiographs and lung scans, pulmonary Ethiodol emboli did not occur. A significant temporary increase in serum bilirubin and liver enzymes followed the procedure but these returned to normal within a week to a month. Periodic needle biopsies of the liver showed Ethiodol droplets initially in the interstitium and lymphatics, and subsequently in hepatocytes, Kupffer's cells and the epithelium of small bile ductules. No hepatic damage was found histologically on long-time follow-up examinations.", "contents": "Hepatography and liver lymphography by retrograde biliary ethiodol infusion: an experimental study in the dog. Ethiodol in dosages of 0.5-3 ml/kg was retrogradely infused with hydrostatic pressure of 50--100 cm water into the biliary system of nine cholecystectomized dogs equipped with a Thomas cannula in the second portion of the duodenum, allowing cannulation of the common bile duct with a Foley catheter under direct vision. A total of 18 examinations were performed. A dense hepatogram and complete visualization of the hepatic lymph nodes were obtained when the infused Ethiodol dosage exceeded the capacity of the biliary system by 10 ml or more. The hepatogram lasted for three to four months and the lymph nodes were opacified for a year and longer. Contrary to angiographic contrast agents, Ethiodol retrogradely infused into the biliary system primarily refluxes from the biliary system to the lymph and not to the blood. Judged by serial chest radiographs and lung scans, pulmonary Ethiodol emboli did not occur. A significant temporary increase in serum bilirubin and liver enzymes followed the procedure but these returned to normal within a week to a month. Periodic needle biopsies of the liver showed Ethiodol droplets initially in the interstitium and lymphatics, and subsequently in hepatocytes, Kupffer's cells and the epithelium of small bile ductules. No hepatic damage was found histologically on long-time follow-up examinations."}
{"id": "PMID:193809", "title": "Oxidative enzymes in the sebaceous glands of the domestic cat.", "content": "The distribution and activities of several oxidative enzymes in various regions of the sebaceous glands of the domestic cat have been studied. The results obtained emphasize the outstanding importance of NADP-linked dehydrogenases for lipogenesis during sebum production. In particular, the reactions for glucose-6-phosphate dehydrogenase were very strong. Among the NAD-linked dehydrogenases investigated, lactate dehydrogenase showed strong activity in the peripheral cells of the sebaceous gland. The reactions for cytochrome oxidase and succinate dehydrogenase were weaker.", "contents": "Oxidative enzymes in the sebaceous glands of the domestic cat. The distribution and activities of several oxidative enzymes in various regions of the sebaceous glands of the domestic cat have been studied. The results obtained emphasize the outstanding importance of NADP-linked dehydrogenases for lipogenesis during sebum production. In particular, the reactions for glucose-6-phosphate dehydrogenase were very strong. Among the NAD-linked dehydrogenases investigated, lactate dehydrogenase showed strong activity in the peripheral cells of the sebaceous gland. The reactions for cytochrome oxidase and succinate dehydrogenase were weaker."}
{"id": "PMID:193827", "title": "Supersaturation by counterperfusion and diffusion of gases.", "content": "Gaseous supersaturation can be induced under steady-state conditions when two inert gases are transmitted in opposite directions across any system comprising a diffusion barrier adjacent to a zone of limited convective capacity. This has many implications for bubble formation in vivo and can explain the occurence of symptoms of decompression sickness without decompression.", "contents": "Supersaturation by counterperfusion and diffusion of gases. Gaseous supersaturation can be induced under steady-state conditions when two inert gases are transmitted in opposite directions across any system comprising a diffusion barrier adjacent to a zone of limited convective capacity. This has many implications for bubble formation in vivo and can explain the occurence of symptoms of decompression sickness without decompression."}
{"id": "PMID:193829", "title": "In vivo aminoacylation of transfer ribonucleic acid in Bacillus subtilis and evidence for differential utilization of lysine-isoaccepting transfer ribonucleic acid species.", "content": "The presence or absence of certain amino acids has different effects on the ability of Bacillus subtilis to sporulate, and the intracellular pool size of amino acids has been reported to vary during sporulation. The idea that these variations might exert a regulatory effect through aminoacylation of transfer ribonucleic acid (tRNA) was investigated by studying the levels of aminoacylation in vivo in the logarithmic or stationary phase of growth. Both the periodate oxidation method and the amino acid analyzer were used to evaluate in vivo aminoacylation. The results indicated that in general the level of aminoacylation of tRNA's remained constant through stage III of sporulation, although there were detectable variations for specific amino acid groups. Our studies also showed that periodate oxidation damaged certain tRNA's; therefore, the results obtained by such a method should be interpreted with caution. Because the damage can affect certain isoaccepting species specifically, the periodate oxidation method cannot be used to establish which isoaccepting species are acylated in vivo. We also investigated the possibility of preferential use of particular tRNA species by polyribosomes. These results demonstrated a preferential use of lysyl-tRNA's at different growth stages. Control mechanisms operating during the early stages of sporulation, therefore, do not affect the overall level of aminoacylation. However, there is an effect on the levels of aminoacylation of specific amino acids and on which isoaccepting species are utilized by the polyribosome system.", "contents": "In vivo aminoacylation of transfer ribonucleic acid in Bacillus subtilis and evidence for differential utilization of lysine-isoaccepting transfer ribonucleic acid species. The presence or absence of certain amino acids has different effects on the ability of Bacillus subtilis to sporulate, and the intracellular pool size of amino acids has been reported to vary during sporulation. The idea that these variations might exert a regulatory effect through aminoacylation of transfer ribonucleic acid (tRNA) was investigated by studying the levels of aminoacylation in vivo in the logarithmic or stationary phase of growth. Both the periodate oxidation method and the amino acid analyzer were used to evaluate in vivo aminoacylation. The results indicated that in general the level of aminoacylation of tRNA's remained constant through stage III of sporulation, although there were detectable variations for specific amino acid groups. Our studies also showed that periodate oxidation damaged certain tRNA's; therefore, the results obtained by such a method should be interpreted with caution. Because the damage can affect certain isoaccepting species specifically, the periodate oxidation method cannot be used to establish which isoaccepting species are acylated in vivo. We also investigated the possibility of preferential use of particular tRNA species by polyribosomes. These results demonstrated a preferential use of lysyl-tRNA's at different growth stages. Control mechanisms operating during the early stages of sporulation, therefore, do not affect the overall level of aminoacylation. However, there is an effect on the levels of aminoacylation of specific amino acids and on which isoaccepting species are utilized by the polyribosome system."}
{"id": "PMID:193830", "title": "Levels of small molecules and enzymes in the mother cell compartment and the forespore of sporulating Bacillus megaterium.", "content": "We have determined the amounts of a number of small molecules and enzymes in the mother cell compartment and the developing forespore during sporulation of Bacillus megaterium. Significant amounts of adenosine 5'-triphosphate and reduced nicotinamide adenine dinucleotide were present in the forespore compartment before accumulation of dipicolinic acid (DPA), but these compounds disappeared as DPA was accumulated. 3-Phosphoglyceric acid (3-PGA) accumulated only within the developing forespore, beginning 1 to 2 h before DPA accumulation. Throughout its development the forespore contained constant levels of enzymes of both 3-PGA synthesis (phosphoglycerate kinase and glyceraldehyde-3-phosphate dehydrogenase) and 3-PGA utilization (phosphoglycerate mutase, enolase, and pyruvate kinase) at levels similar to those in the mother cell and the dormant spore. Despite the presence of enzymes for 3-PGA utilization, this compound was stable within isolated forespores. Two acid-soluble proteins (A and B proteins) also accumulated only in the forespore, beginning 1 to 2 h before DPA accumulation. At this time the specific protease involved in degradation of the A and B proteins during germination also appeared, but only in the forespore compartment. Nevertheless, the A and B proteins were stable within isolated forespores. Arginine and glutamic acid accumulated within the forespore in parallel with DPA accumulation. The forespore also contained the enzyme arginase at a level similar to that in the mother cell and a level of glutamic acid decarboxylase 2- to 25-fold higher than that in the mother cell, depending on when in sporulation the forespores were isolated. The specific activities of several other enzymes (protease active on hemoglobin, ornithine transcarbamylase, malate dehydrogenase, aconitase, and isocitrate dehydrogenase) in forespores were about 10% or less of the values in the mother cell. Aminopeptidase was present at similar levels in both compartments; threonine deaminase was not found in either compartment.", "contents": "Levels of small molecules and enzymes in the mother cell compartment and the forespore of sporulating Bacillus megaterium. We have determined the amounts of a number of small molecules and enzymes in the mother cell compartment and the developing forespore during sporulation of Bacillus megaterium. Significant amounts of adenosine 5'-triphosphate and reduced nicotinamide adenine dinucleotide were present in the forespore compartment before accumulation of dipicolinic acid (DPA), but these compounds disappeared as DPA was accumulated. 3-Phosphoglyceric acid (3-PGA) accumulated only within the developing forespore, beginning 1 to 2 h before DPA accumulation. Throughout its development the forespore contained constant levels of enzymes of both 3-PGA synthesis (phosphoglycerate kinase and glyceraldehyde-3-phosphate dehydrogenase) and 3-PGA utilization (phosphoglycerate mutase, enolase, and pyruvate kinase) at levels similar to those in the mother cell and the dormant spore. Despite the presence of enzymes for 3-PGA utilization, this compound was stable within isolated forespores. Two acid-soluble proteins (A and B proteins) also accumulated only in the forespore, beginning 1 to 2 h before DPA accumulation. At this time the specific protease involved in degradation of the A and B proteins during germination also appeared, but only in the forespore compartment. Nevertheless, the A and B proteins were stable within isolated forespores. Arginine and glutamic acid accumulated within the forespore in parallel with DPA accumulation. The forespore also contained the enzyme arginase at a level similar to that in the mother cell and a level of glutamic acid decarboxylase 2- to 25-fold higher than that in the mother cell, depending on when in sporulation the forespores were isolated. The specific activities of several other enzymes (protease active on hemoglobin, ornithine transcarbamylase, malate dehydrogenase, aconitase, and isocitrate dehydrogenase) in forespores were about 10% or less of the values in the mother cell. Aminopeptidase was present at similar levels in both compartments; threonine deaminase was not found in either compartment."}
{"id": "PMID:193831", "title": "Selective incorporation of membrane proteins into proteoliposomes of different compositions.", "content": "1. Cytochrome oxidase was incorporated into preformed liposomes containing phosphatidylserine. When confronted with a mixture of liposomes, some containing phosphatidylserine and some without it, the enzyme was incorporated only into the phosphatidylserine-containing liposomes. 2. The hydrophobic proteins of the oligomycin-sensitive ATPase incubated in the presence of a mixture of liposomes with and without cytochrome oxidase were preferentially incorporated into cytochrome oxidase-containing liposomes. This selectivity was abolished by either cytochrome c or ascorbate. 3. Cytochrome oxidase incubated in the presence of a mixture of liposomes with and without the hydrophobic proteins of the ATPase was preferentially incorporated into liposomes that did not contain the hydrophobic proteins. 4. Cytochrome oxidase and the oligomycin-sensitive ATPase were preferentially incorporated into pure liposomes over bacteriorhodopsin-containing vesicles. 5. Reduced coenzyme Q (QH2)-cytochrome c reductase was incorporated randomly when incubated in the presence of a mixture of pure liposomes and liposomes containing the hydrophobic proteins of the ATPase complex. 6. The significance of the incorporation procedure as a model for membrane biogenesis is discussed.", "contents": "Selective incorporation of membrane proteins into proteoliposomes of different compositions. 1. Cytochrome oxidase was incorporated into preformed liposomes containing phosphatidylserine. When confronted with a mixture of liposomes, some containing phosphatidylserine and some without it, the enzyme was incorporated only into the phosphatidylserine-containing liposomes. 2. The hydrophobic proteins of the oligomycin-sensitive ATPase incubated in the presence of a mixture of liposomes with and without cytochrome oxidase were preferentially incorporated into cytochrome oxidase-containing liposomes. This selectivity was abolished by either cytochrome c or ascorbate. 3. Cytochrome oxidase incubated in the presence of a mixture of liposomes with and without the hydrophobic proteins of the ATPase was preferentially incorporated into liposomes that did not contain the hydrophobic proteins. 4. Cytochrome oxidase and the oligomycin-sensitive ATPase were preferentially incorporated into pure liposomes over bacteriorhodopsin-containing vesicles. 5. Reduced coenzyme Q (QH2)-cytochrome c reductase was incorporated randomly when incubated in the presence of a mixture of pure liposomes and liposomes containing the hydrophobic proteins of the ATPase complex. 6. The significance of the incorporation procedure as a model for membrane biogenesis is discussed."}
{"id": "PMID:193832", "title": "Effects of estrogen, glucocorticoid, glucagon, and adenosine 3':5'-monophosphate on catalytic activity, amount, and rate of de novo synthesis of hepatic histidase.", "content": "The mechanisms by which estrogen, glucocorticoid, glucagon, and adenosine 3':5'-monophosphate (cAMP), regulators which participate in the postnatal development of rat liver histidase, elevate the catalytic activity of this enzyme have been explored. A monospecific antibody against homogeneously purified preparations of rat liver histidase has been elaborated in the goat. Employing this antibody in immunotitration experiments, it has been demonstrated that the elevations of hepatic histidase activity elicited by administration in vivo of estradiol-17beta, cortisol acetate, glucagon, and N6,O2'-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cAMP) are paralleled, in each instance, by equivalent increments in immunoprecipitable histidase protein. Following administration of each of the three hormones and dibutyryl cAMP, rates of [14C]leucine incorporation in vivo into rat liver histidase, isolated by immunoprecipitation, relative to incorporation rates into total soluble hepatic protein, increase in magnitudes which are comparable to increases in enzyme amount and catalytic activity. It is thus inferred that estrogen, glucocorticoids, and glucagon, via cAMP, each regulate rat liver histidase development at specific postnatal stages by inducing increases in histidase biosynthetic rates.", "contents": "Effects of estrogen, glucocorticoid, glucagon, and adenosine 3':5'-monophosphate on catalytic activity, amount, and rate of de novo synthesis of hepatic histidase. The mechanisms by which estrogen, glucocorticoid, glucagon, and adenosine 3':5'-monophosphate (cAMP), regulators which participate in the postnatal development of rat liver histidase, elevate the catalytic activity of this enzyme have been explored. A monospecific antibody against homogeneously purified preparations of rat liver histidase has been elaborated in the goat. Employing this antibody in immunotitration experiments, it has been demonstrated that the elevations of hepatic histidase activity elicited by administration in vivo of estradiol-17beta, cortisol acetate, glucagon, and N6,O2'-dibutyryl adenosine 3':5'-monophosphate (dibutyryl cAMP) are paralleled, in each instance, by equivalent increments in immunoprecipitable histidase protein. Following administration of each of the three hormones and dibutyryl cAMP, rates of [14C]leucine incorporation in vivo into rat liver histidase, isolated by immunoprecipitation, relative to incorporation rates into total soluble hepatic protein, increase in magnitudes which are comparable to increases in enzyme amount and catalytic activity. It is thus inferred that estrogen, glucocorticoids, and glucagon, via cAMP, each regulate rat liver histidase development at specific postnatal stages by inducing increases in histidase biosynthetic rates."}
{"id": "PMID:193834", "title": "Effects of chaotropic agents versus detergents on dihydroorotate dehydrogenase.", "content": "As chaotropic salts are generally believed to affect water structure in a manner which increases lipophilicity of water, they may seem to be capable of substituting for detergents in the solubilization of particulate enzyme. Although solubilization either by detergents or by chaotropic salts has been demonstrated with several membrane proteins, the effects these agents have on the properties and activity of an enzyme may be quite different. This is illustrated by the effects on mammalian mitochondrial dihydroorotate dehydrogenase. Stability of the solubilized enzymic activity is dependnet on the presence of a detergent and maximum enzymic activity is observed at the critical micelle concentration of the detergent. Addition of low concentrations of various anions of the chaotropic series further enhances activity while higher concentrations of these anions, although increasing solubility of the enzyme, irreversibly inhibit catalysis.", "contents": "Effects of chaotropic agents versus detergents on dihydroorotate dehydrogenase. As chaotropic salts are generally believed to affect water structure in a manner which increases lipophilicity of water, they may seem to be capable of substituting for detergents in the solubilization of particulate enzyme. Although solubilization either by detergents or by chaotropic salts has been demonstrated with several membrane proteins, the effects these agents have on the properties and activity of an enzyme may be quite different. This is illustrated by the effects on mammalian mitochondrial dihydroorotate dehydrogenase. Stability of the solubilized enzymic activity is dependnet on the presence of a detergent and maximum enzymic activity is observed at the critical micelle concentration of the detergent. Addition of low concentrations of various anions of the chaotropic series further enhances activity while higher concentrations of these anions, although increasing solubility of the enzyme, irreversibly inhibit catalysis."}
{"id": "PMID:193835", "title": "Determination of the nucleotide sequence of part of the regulatory region for the galactose operon from Escherichia coli.", "content": "We have determined the sequence of 59 base pairs in the DNA preceding the site for initiation of transcription in the galactose operon. DNA from a lambdagal transducing phage was digested with restriction endonucleases to obtain a DNA fragment from the gal regulatory region. This fragment extends from 59 base pairs prior to the transcription initiation site through the 45 base pairs which specify the 5'-terminal sequence of gal mRNA. Analyses of RNA transcripts derived from this fragment and a variety of direct DNA sequence analyses allowed us to deduce the following sequence for the DNA in this fragment: (formula: see text) Position +1 corresponds to the site for initiation of gal mRNA synthesized in the presence of cyclic AMP and its receptor protein, CRP. Transcription experiments indicate, however, that this fragment lacks some element of the gal promoter required for the stimulation of transcription by CRP-cAMP. There are, nonetheless, some similarities between the gal sequence preceding the transcription start site and the sequences of other promoter regions. These include the heptamer sequence T-A-T-G-G-T-T (--12 to --8) and the sequence A-C-A-C-T-T-T (--36 to --30).", "contents": "Determination of the nucleotide sequence of part of the regulatory region for the galactose operon from Escherichia coli. We have determined the sequence of 59 base pairs in the DNA preceding the site for initiation of transcription in the galactose operon. DNA from a lambdagal transducing phage was digested with restriction endonucleases to obtain a DNA fragment from the gal regulatory region. This fragment extends from 59 base pairs prior to the transcription initiation site through the 45 base pairs which specify the 5'-terminal sequence of gal mRNA. Analyses of RNA transcripts derived from this fragment and a variety of direct DNA sequence analyses allowed us to deduce the following sequence for the DNA in this fragment: (formula: see text) Position +1 corresponds to the site for initiation of gal mRNA synthesized in the presence of cyclic AMP and its receptor protein, CRP. Transcription experiments indicate, however, that this fragment lacks some element of the gal promoter required for the stimulation of transcription by CRP-cAMP. There are, nonetheless, some similarities between the gal sequence preceding the transcription start site and the sequences of other promoter regions. These include the heptamer sequence T-A-T-G-G-T-T (--12 to --8) and the sequence A-C-A-C-T-T-T (--36 to --30)."}
{"id": "PMID:193837", "title": "Acquisition of increased hormone sensitivity during in vitro adipocyte development.", "content": "Murine 3T3-L1 fibroblasts enter a differentiation program subsequent to prolonged maintenance in the confluent state and develop into adipocytes. The hormone sensitivity of adenylate cyclase and the physiological responsiveness to insulin were compared in 3T3-L1 preadipocytes and adipocytes. The following observations, comprising several distinct categories of hormone responsiveness, were made. (a) (2.5 micronM) isoproterenol stimulated adenylate cyclase 15-fold in adipocyte homogenates, but only 2.5-fold in preadipocyte preparations, suggesting a considerable magnification in beta-adrenergic responsiveness during development. (b) A totally new control element, adrenocorticotropic hormone responsiveness, was incorporated into the adenylate cyclase system of the adipocytes. (c) Sensitivity to prostaglandin E1 was observed in both preadipocytes and adipocytes, but no change in responsiveness could be detected in the differentiated cells. (d) Glucagon-sensitive adenylate cyclase could not be detected in either preadipocytes or adipocytes. (e) Both preadipocytes and adipocytes possess considerable insulin binding activity, but near physiological levels of insulin stimulate the conversion of glucose to CO2 and lipid only in the differentiated cells.", "contents": "Acquisition of increased hormone sensitivity during in vitro adipocyte development. Murine 3T3-L1 fibroblasts enter a differentiation program subsequent to prolonged maintenance in the confluent state and develop into adipocytes. The hormone sensitivity of adenylate cyclase and the physiological responsiveness to insulin were compared in 3T3-L1 preadipocytes and adipocytes. The following observations, comprising several distinct categories of hormone responsiveness, were made. (a) (2.5 micronM) isoproterenol stimulated adenylate cyclase 15-fold in adipocyte homogenates, but only 2.5-fold in preadipocyte preparations, suggesting a considerable magnification in beta-adrenergic responsiveness during development. (b) A totally new control element, adrenocorticotropic hormone responsiveness, was incorporated into the adenylate cyclase system of the adipocytes. (c) Sensitivity to prostaglandin E1 was observed in both preadipocytes and adipocytes, but no change in responsiveness could be detected in the differentiated cells. (d) Glucagon-sensitive adenylate cyclase could not be detected in either preadipocytes or adipocytes. (e) Both preadipocytes and adipocytes possess considerable insulin binding activity, but near physiological levels of insulin stimulate the conversion of glucose to CO2 and lipid only in the differentiated cells."}
{"id": "PMID:193838", "title": "Inhibition of carbamyl phosphate synthetase by P1, P5-di(adenosine 5')-pentaphosphate: evidence for two ATP binding sites.", "content": "Studies on the effect of a series of alpha, omega-diadenosine 5'-polyphosphate (ApnA; n = 2 to 6) on carbamyl phosphate synthetase showed that only Ap5A is an effective inhibitor. Ap5A also inhibits two partial reactions catalyzed by the enzyme: bicarbonate-dependent ATPase and ATP synthesis from carbamyl phosphate and ADP. The data indicate that Ap5A binds to the enzyme sites that interact with ATP. Of a variety of ATP-utilizing enzymes (kinases, hydrolases, synthetases), only adenylate kinase (Leinhard, G. E., and Secemski, I. I. (1973) J. Biol. Chem. 248, 1121--1123) and carbamyl phosphate synthetase are inhibited by Ap5A. The present findings provide strong evidence that carbamyl phosphate synthetase has two separate binding sites for ATP in which the gamma-phosphate moeities of ATP are bound in close proximity to the bicarbonate binding site of the enzyme.", "contents": "Inhibition of carbamyl phosphate synthetase by P1, P5-di(adenosine 5')-pentaphosphate: evidence for two ATP binding sites. Studies on the effect of a series of alpha, omega-diadenosine 5'-polyphosphate (ApnA; n = 2 to 6) on carbamyl phosphate synthetase showed that only Ap5A is an effective inhibitor. Ap5A also inhibits two partial reactions catalyzed by the enzyme: bicarbonate-dependent ATPase and ATP synthesis from carbamyl phosphate and ADP. The data indicate that Ap5A binds to the enzyme sites that interact with ATP. Of a variety of ATP-utilizing enzymes (kinases, hydrolases, synthetases), only adenylate kinase (Leinhard, G. E., and Secemski, I. I. (1973) J. Biol. Chem. 248, 1121--1123) and carbamyl phosphate synthetase are inhibited by Ap5A. The present findings provide strong evidence that carbamyl phosphate synthetase has two separate binding sites for ATP in which the gamma-phosphate moeities of ATP are bound in close proximity to the bicarbonate binding site of the enzyme."}
{"id": "PMID:193839", "title": "Reduced concentrations of Z protein in Morris hepatomas. Possible role in abnormal regulation of lipid metabolism.", "content": "The cytoplasmic concentration of Z protein (Mr approximately 12,000) was significantly reduced in a series of implanted Morris hepatomas with varying degrees of differentiation. Approximately half of the [14C]palmitoyl-CoA added to cytosol fractions from control or host livers was bound to the Z protein region whereas a much smaller proportion was bound to this region in the cytosol of nine Morris hepatomas studied. The possible implications of these findings are discussed in relation to the abnormal regulation of lipid metabolism in hepatomas.", "contents": "Reduced concentrations of Z protein in Morris hepatomas. Possible role in abnormal regulation of lipid metabolism. The cytoplasmic concentration of Z protein (Mr approximately 12,000) was significantly reduced in a series of implanted Morris hepatomas with varying degrees of differentiation. Approximately half of the [14C]palmitoyl-CoA added to cytosol fractions from control or host livers was bound to the Z protein region whereas a much smaller proportion was bound to this region in the cytosol of nine Morris hepatomas studied. The possible implications of these findings are discussed in relation to the abnormal regulation of lipid metabolism in hepatomas."}
{"id": "PMID:193840", "title": "Calcium fluxes in isolated acinar cells from rat parotid. Effect of adrenergic and cholinergic stimulation.", "content": "Rat parotid acinar cells dispersed by a combination of enzymatic treatments remain sensitive to adrenergic and cholinergic agonists. Previous studies have implicated Ca2+ in both adrenergic and cholinergic responses. This paper describes the effects of adrenergic and cholinergic stimulation upon 45Ca2+ fluxes in isolated parotid acinar cells. Suspensions of dispersed cells took up 45Ca2+ from the medium. The net rate of isotope influx was increased by the adrenergic agonists epinephrine, norepinephrine, isoproterenol, and phenylephrine, and by the cholinergic agonists acetylcholine and carbamylcholine. In 1 mM Ca2+, epinephrine was capable of increasing the 45Ca2+ influx in 40 min to three times that of resting cells. Isoproterenol, a beta-adrenergic agonist, was only half as effective as epinephrine in stimulating maximal calcium uptake although it was equally effective in stimulating maximal amylase release in the same cells. Experiments with the alpha-adrenergic antagonist phentolamine, the beta-adrenergic antagonist propranolol, and the cholinergic antagonist atropine confirmed that alpha- and beta-adrenergic and cholinergic stimulation each had a direct stimulatory effect on 45Ca2+ uptake. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate also caused some stimulation of net calcium uptake. Direct measurement of Ca2+ efflux indicated that the increased calcium uptake in the presence of epinephrine was not the indirect result of a decrease in efflux. The rates of both basal and epinephrine-stimulated calcium uptake increased with increasing calcium concentration in the medium. Epinephrine had little effect on the rate of calcium uptake at 0.15 mM Ca2+. Although the energy poison NaCN had little effect on the basal rate of calcium uptake, the stimulable component of calcium uptake was inhibited by NaCN at all calcium concentrations tested (0.2 to 4.1 mM).", "contents": "Calcium fluxes in isolated acinar cells from rat parotid. Effect of adrenergic and cholinergic stimulation. Rat parotid acinar cells dispersed by a combination of enzymatic treatments remain sensitive to adrenergic and cholinergic agonists. Previous studies have implicated Ca2+ in both adrenergic and cholinergic responses. This paper describes the effects of adrenergic and cholinergic stimulation upon 45Ca2+ fluxes in isolated parotid acinar cells. Suspensions of dispersed cells took up 45Ca2+ from the medium. The net rate of isotope influx was increased by the adrenergic agonists epinephrine, norepinephrine, isoproterenol, and phenylephrine, and by the cholinergic agonists acetylcholine and carbamylcholine. In 1 mM Ca2+, epinephrine was capable of increasing the 45Ca2+ influx in 40 min to three times that of resting cells. Isoproterenol, a beta-adrenergic agonist, was only half as effective as epinephrine in stimulating maximal calcium uptake although it was equally effective in stimulating maximal amylase release in the same cells. Experiments with the alpha-adrenergic antagonist phentolamine, the beta-adrenergic antagonist propranolol, and the cholinergic antagonist atropine confirmed that alpha- and beta-adrenergic and cholinergic stimulation each had a direct stimulatory effect on 45Ca2+ uptake. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate also caused some stimulation of net calcium uptake. Direct measurement of Ca2+ efflux indicated that the increased calcium uptake in the presence of epinephrine was not the indirect result of a decrease in efflux. The rates of both basal and epinephrine-stimulated calcium uptake increased with increasing calcium concentration in the medium. Epinephrine had little effect on the rate of calcium uptake at 0.15 mM Ca2+. Although the energy poison NaCN had little effect on the basal rate of calcium uptake, the stimulable component of calcium uptake was inhibited by NaCN at all calcium concentrations tested (0.2 to 4.1 mM)."}
{"id": "PMID:193841", "title": "Imidazole, the ligand trans to mercaptide in ferric cytochrome P-450. An EPR study of proteins and model compounds.", "content": "A crystal field analysis of EPR data for various low spin ferric cytochromes P-450 suggests that in all of them, regardless of source or method of induction, the heme ligands are a sulfur atom, presumably from cysteine, and an imidazole from histidine. The imidazole can be displaced in the ferric protein by cyanide, guanidine, or by an amine, analogous to its displacement by CO or NO in the ferrous protein. The resulting changes in the EPR parameters for the ferric protein are consistent with similar substitutions in heme thiol model compounds. The analysis of the latter can be understood on the basis of alterations of the electronic structure of the ligands to the heme iron.", "contents": "Imidazole, the ligand trans to mercaptide in ferric cytochrome P-450. An EPR study of proteins and model compounds. A crystal field analysis of EPR data for various low spin ferric cytochromes P-450 suggests that in all of them, regardless of source or method of induction, the heme ligands are a sulfur atom, presumably from cysteine, and an imidazole from histidine. The imidazole can be displaced in the ferric protein by cyanide, guanidine, or by an amine, analogous to its displacement by CO or NO in the ferrous protein. The resulting changes in the EPR parameters for the ferric protein are consistent with similar substitutions in heme thiol model compounds. The analysis of the latter can be understood on the basis of alterations of the electronic structure of the ligands to the heme iron."}
{"id": "PMID:193843", "title": "L-Arginine kinase from tobacco hornworm, Manduca sexta (L.). Purification, properties, and interaction with L-canavanine.", "content": "Arginine kinase (adenosine 5'-triphosphate: L-arginine phosphotransferase, EC 2.7.3.3) was purified from the larvae of the tobacco hornworm, Manduca sexta (L). This enzyme catalyzes the production of L-phosphoarginine, which is the principal reserve of high energy phosphate compounds in insect muscle. The enzyme also phosphorylates L-canavanine, a guanidinooxy analogue of arginine which severely disrupts all developmental stages of this insect. Evaluations of certain kinetic and thermodynamic parameters of the reactions with arginine and canavanine suggest that reactions known to be much more sensitive to canavanine, such as protein synthesis or genome expression, rather than phosphagen formation and function account for the pronounced toxicity of canavanine in this insect. Sedimentation equilibrium and electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate indicate that this insect enzyme has a molecular weight of about 40,000. This value is consistent with molecular weights of arginine kinases of non-insect arthropods. Its amino acid composition is also very similar to that of other arthropod arginine kinases. Km values for the enzyme are: L-arginine, 0.5 mM; Mg-ATP, 2.5 mM; L-canavanine, 22 mM; L-phosphoarginine, 0.7 mM; Mg-ADP, 0.45 mM; and L-phosphocanavanine, 27 mM. Turnover numbers (expressed as moles of product per min per mol of enzyme) are: L-arginine, 8,320; L-canavanine, 1,635; L-phosphoarginine, 25,875; and L-phosphocanavanine, 3,040. The apparent equilibrium constants at 37 degrees for phosphagen formation are 0.44 with arginine and 0.1 with canavanine. A procedure for L-phosphocanavanine synthesis is also presented.", "contents": "L-Arginine kinase from tobacco hornworm, Manduca sexta (L.). Purification, properties, and interaction with L-canavanine. Arginine kinase (adenosine 5'-triphosphate: L-arginine phosphotransferase, EC 2.7.3.3) was purified from the larvae of the tobacco hornworm, Manduca sexta (L). This enzyme catalyzes the production of L-phosphoarginine, which is the principal reserve of high energy phosphate compounds in insect muscle. The enzyme also phosphorylates L-canavanine, a guanidinooxy analogue of arginine which severely disrupts all developmental stages of this insect. Evaluations of certain kinetic and thermodynamic parameters of the reactions with arginine and canavanine suggest that reactions known to be much more sensitive to canavanine, such as protein synthesis or genome expression, rather than phosphagen formation and function account for the pronounced toxicity of canavanine in this insect. Sedimentation equilibrium and electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate indicate that this insect enzyme has a molecular weight of about 40,000. This value is consistent with molecular weights of arginine kinases of non-insect arthropods. Its amino acid composition is also very similar to that of other arthropod arginine kinases. Km values for the enzyme are: L-arginine, 0.5 mM; Mg-ATP, 2.5 mM; L-canavanine, 22 mM; L-phosphoarginine, 0.7 mM; Mg-ADP, 0.45 mM; and L-phosphocanavanine, 27 mM. Turnover numbers (expressed as moles of product per min per mol of enzyme) are: L-arginine, 8,320; L-canavanine, 1,635; L-phosphoarginine, 25,875; and L-phosphocanavanine, 3,040. The apparent equilibrium constants at 37 degrees for phosphagen formation are 0.44 with arginine and 0.1 with canavanine. A procedure for L-phosphocanavanine synthesis is also presented."}
{"id": "PMID:193844", "title": "Characterization of triton X-100-solubilized prostaglandin E binding protein of rat liver plasma membranes.", "content": "Rat liver plasma membranes bind prostaglandins E1 and E2 (PGE) with high affinity and specificity. We have solubilized plasma membranes, prelabeled with radioactive PGE1, in water solutions of Triton X-100. We sedimented this material into sucrose density gradient containing H2O and D2O. From numerical integration of the sedimentation equation, taking explicitly into account the density and viscosity gradients present during the centrifugation, we have determined a value of s20,w = 5.6 to 5.7 X 10(-13) s and a partial specific volume, v = 0.80 to 0.81 cm3/g, for the PGE binding protein-Triton X-100 composed of 60% (w/w) protein and 40% (w/w) detergent. Gel filtration in water solutions of Triton X-100 gives a Stokes radius of 53 A for the complex. These data imply a molecular weight of 105,000 for the detergent-free binding protein and a frictional ratio of 1.3 for the complex. If the detergent is bound to the protein in a monolayer, about 40% of the PGE binding protein's surface would be covered with detergent. The procedures used in the analysis of the sedimentation behavior of the PGE binding protein-detergent complex, when coupled with a gel filtration measurement of the Stokes radius, allow valid determination of the size, shape, and extent of detergent binding of a wide variety of membrane proteins, even when they are present as minor components of complex mixtures.", "contents": "Characterization of triton X-100-solubilized prostaglandin E binding protein of rat liver plasma membranes. Rat liver plasma membranes bind prostaglandins E1 and E2 (PGE) with high affinity and specificity. We have solubilized plasma membranes, prelabeled with radioactive PGE1, in water solutions of Triton X-100. We sedimented this material into sucrose density gradient containing H2O and D2O. From numerical integration of the sedimentation equation, taking explicitly into account the density and viscosity gradients present during the centrifugation, we have determined a value of s20,w = 5.6 to 5.7 X 10(-13) s and a partial specific volume, v = 0.80 to 0.81 cm3/g, for the PGE binding protein-Triton X-100 composed of 60% (w/w) protein and 40% (w/w) detergent. Gel filtration in water solutions of Triton X-100 gives a Stokes radius of 53 A for the complex. These data imply a molecular weight of 105,000 for the detergent-free binding protein and a frictional ratio of 1.3 for the complex. If the detergent is bound to the protein in a monolayer, about 40% of the PGE binding protein's surface would be covered with detergent. The procedures used in the analysis of the sedimentation behavior of the PGE binding protein-detergent complex, when coupled with a gel filtration measurement of the Stokes radius, allow valid determination of the size, shape, and extent of detergent binding of a wide variety of membrane proteins, even when they are present as minor components of complex mixtures."}
{"id": "PMID:193846", "title": "3(17)beta-Hydroxysteroid Dehydrogenase of Pseudomonas testosteroni. Ligand binding properties.", "content": "The binding of NAD and NADH to electrophoretically pure 3(17)beta-hydroxysteroid dehydrogenase of Pseudomonas testosteroni was determined by Fluorescence spectroscopy and gel filtration. Four moles of cofactor are bound/mol of tetrameric enzyme; the binding sites are equivalent and independent. The dissociation constants for NAD and NADH are 16 and 0.25 micronM, respectively. As measured by gel filtration in the absence of cofactor, 0.4 mol of estradiol-17 beta is bound/mol of tetrameric enzyme. Data obtained from isotope exchange at equilibrium indicate that the binding of the cofactor to the enzyme is favored over the binding of steroid, although each may bind in the absence of the other. The rates of cofactor dissociation from the ternary complexes are slower than the rates of steroid dissociation; cofactor dissociation is probably the rate-limiting step. Cofactor analogs modified in the pyridine moiety are cosubstrates, whereas modified adenine derivatives are not. The enzyme also utilized as substrate a number of potential steroid affinity labels; no enzyme inactivation by these compounds was observed.", "contents": "3(17)beta-Hydroxysteroid Dehydrogenase of Pseudomonas testosteroni. Ligand binding properties. The binding of NAD and NADH to electrophoretically pure 3(17)beta-hydroxysteroid dehydrogenase of Pseudomonas testosteroni was determined by Fluorescence spectroscopy and gel filtration. Four moles of cofactor are bound/mol of tetrameric enzyme; the binding sites are equivalent and independent. The dissociation constants for NAD and NADH are 16 and 0.25 micronM, respectively. As measured by gel filtration in the absence of cofactor, 0.4 mol of estradiol-17 beta is bound/mol of tetrameric enzyme. Data obtained from isotope exchange at equilibrium indicate that the binding of the cofactor to the enzyme is favored over the binding of steroid, although each may bind in the absence of the other. The rates of cofactor dissociation from the ternary complexes are slower than the rates of steroid dissociation; cofactor dissociation is probably the rate-limiting step. Cofactor analogs modified in the pyridine moiety are cosubstrates, whereas modified adenine derivatives are not. The enzyme also utilized as substrate a number of potential steroid affinity labels; no enzyme inactivation by these compounds was observed."}
{"id": "PMID:193848", "title": "Endogenous protein kinase inhibitors. Purification, characterization, and distribution in different tissues.", "content": "A thermostable inhibition of ATP-protein phosphotransferase (EC 2.7.1.37) (protein kinase) which is present in crude tissue extracts has been resolved by gel chromatography (Sephadex G-100) into two molecular forms. These two forms will be referred to as type I and type II inhibitor. The type I inhibitor (Mr approximately or equal to 24,000) is specific for cAMP-dependent protein kinase and corresponds to the inhibitor described earlier (Walsh, D. A., Ashby, C. D., Gonzalez, C., Calkins, D., Fisher, E. H., and Krebs, E. G. (1971) J. Biol. Chem. 246, 1977-1985). The type II inhibitor (Mr approximately or equal to 15,000) competes for the enzyme with various substrate proteins (histone, alpha-casein, and Leu-Arg-Arg-Ala-Ser-Leu-Gly (kemptide). The type II inhibitor blocks protein phosphorylation catalyzed by several types of protein kinases (cAMP- and cGMP-dependent or cyclic nucleotide-independent protein kinases). The type II inhibitor from rat brain has been purified 1500-fold; this protein is thermostable, has acidic characteristics, and does not require Ca2+ ions for its activity. Different ratios and concentrations of type I and type II inhibitors of protein kinase are found in rat skeletal muscle, pancreas, cerebellum and corpus striatum, and in lobster tail muscle.", "contents": "Endogenous protein kinase inhibitors. Purification, characterization, and distribution in different tissues. A thermostable inhibition of ATP-protein phosphotransferase (EC 2.7.1.37) (protein kinase) which is present in crude tissue extracts has been resolved by gel chromatography (Sephadex G-100) into two molecular forms. These two forms will be referred to as type I and type II inhibitor. The type I inhibitor (Mr approximately or equal to 24,000) is specific for cAMP-dependent protein kinase and corresponds to the inhibitor described earlier (Walsh, D. A., Ashby, C. D., Gonzalez, C., Calkins, D., Fisher, E. H., and Krebs, E. G. (1971) J. Biol. Chem. 246, 1977-1985). The type II inhibitor (Mr approximately or equal to 15,000) competes for the enzyme with various substrate proteins (histone, alpha-casein, and Leu-Arg-Arg-Ala-Ser-Leu-Gly (kemptide). The type II inhibitor blocks protein phosphorylation catalyzed by several types of protein kinases (cAMP- and cGMP-dependent or cyclic nucleotide-independent protein kinases). The type II inhibitor from rat brain has been purified 1500-fold; this protein is thermostable, has acidic characteristics, and does not require Ca2+ ions for its activity. Different ratios and concentrations of type I and type II inhibitors of protein kinase are found in rat skeletal muscle, pancreas, cerebellum and corpus striatum, and in lobster tail muscle."}
{"id": "PMID:193851", "title": "Interaction of canine and swine lipoproteins with the low density lipoprotein receptor of fibroblasts as correlated with heparin/manganese precipitability.", "content": "Canine HDL1 and canine and swine HDLc were fractionated into several lipoprotein subpopulations by heparin/manganese precipitation. The ability of the various subfractions of HDL1 or HDLc to compete with 125I-labeled low density lipoproteins (LDL) for binding and degradation by human fibroblasts was compared. The HDL1 or HDLc which precipitated at the lowest concentration of heparin (a concentration which precipitates LDL) were the most effective in competing with 125I-LDL for binding, internalization, and degradation. A striking characteristic of these lipoproteins was the occurrence of a prominence of the arginine-rich apoprotein. The HDL1 or HDLc subfractions which were not precipitated by heparin/managanese lacked detectable arginine-rich apoprotein and did not compete significantly with the 125I-LDL for binding and degradation. Furthermore, the lipid to protein ratio differed in the precipitable and nonprecipitable lipoproteins, with those which were most efficiently bound and degraded containing more cholesterol. Specific lipoprotein interaction with heparin and with the cell surface receptors may occur by a common mechanism; namely, through a positively charged region on the lipoprotein surface which may reside with the B and arginine-rich apoproteins.", "contents": "Interaction of canine and swine lipoproteins with the low density lipoprotein receptor of fibroblasts as correlated with heparin/manganese precipitability. Canine HDL1 and canine and swine HDLc were fractionated into several lipoprotein subpopulations by heparin/manganese precipitation. The ability of the various subfractions of HDL1 or HDLc to compete with 125I-labeled low density lipoproteins (LDL) for binding and degradation by human fibroblasts was compared. The HDL1 or HDLc which precipitated at the lowest concentration of heparin (a concentration which precipitates LDL) were the most effective in competing with 125I-LDL for binding, internalization, and degradation. A striking characteristic of these lipoproteins was the occurrence of a prominence of the arginine-rich apoprotein. The HDL1 or HDLc subfractions which were not precipitated by heparin/managanese lacked detectable arginine-rich apoprotein and did not compete significantly with the 125I-LDL for binding and degradation. Furthermore, the lipid to protein ratio differed in the precipitable and nonprecipitable lipoproteins, with those which were most efficiently bound and degraded containing more cholesterol. Specific lipoprotein interaction with heparin and with the cell surface receptors may occur by a common mechanism; namely, through a positively charged region on the lipoprotein surface which may reside with the B and arginine-rich apoproteins."}
{"id": "PMID:193852", "title": "Fatty acid enhancement of human serum albumin binding properties. A spin label study.", "content": "The introduction of a new spin-labeled anionic ligand, 1-gamma-aminobutyrate-5-N-(1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidinyl)-2,4-dinitrobenzene, is reported. Under the experimental conditions, the first molar equivalent of this ligand is 93% bound to human serum albumin. With the addition of palmitate, the free spin label concentration decreases greatly, by almost 80%, in the presence of a fatty acid:albumin ratio of 3:1 to 4:1. The spectral characteristics of the bound spin label are also affected. The changes seen in the intensity of and the splitting between the high and low field extrema are indicative of perturbations of the protein molecule. It is seen then that the binding of each molar equivalent of fatty acid effects the conformation state of albumin and allosterically affects albumin binding properties. Computer spectral subtractions, furthermore, suggest that the binding of the first molar equivalent of palmitate specifically increases the affinity of the first two 1-gamma-amino-butyrate-5-N-(1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidinyl)-2,4-dinitrobenzene binding sites. The present results indicate that fluctuations in serum free fatty acid levels within the physiological range may have a major modulatory effect on the free serum levels of certain drugs and/or physiological substances that bind to albumin.", "contents": "Fatty acid enhancement of human serum albumin binding properties. A spin label study. The introduction of a new spin-labeled anionic ligand, 1-gamma-aminobutyrate-5-N-(1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidinyl)-2,4-dinitrobenzene, is reported. Under the experimental conditions, the first molar equivalent of this ligand is 93% bound to human serum albumin. With the addition of palmitate, the free spin label concentration decreases greatly, by almost 80%, in the presence of a fatty acid:albumin ratio of 3:1 to 4:1. The spectral characteristics of the bound spin label are also affected. The changes seen in the intensity of and the splitting between the high and low field extrema are indicative of perturbations of the protein molecule. It is seen then that the binding of each molar equivalent of fatty acid effects the conformation state of albumin and allosterically affects albumin binding properties. Computer spectral subtractions, furthermore, suggest that the binding of the first molar equivalent of palmitate specifically increases the affinity of the first two 1-gamma-amino-butyrate-5-N-(1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidinyl)-2,4-dinitrobenzene binding sites. The present results indicate that fluctuations in serum free fatty acid levels within the physiological range may have a major modulatory effect on the free serum levels of certain drugs and/or physiological substances that bind to albumin."}
{"id": "PMID:193854", "title": "Cyclic AMP gradient in migrating pseudoplasmodia of the cellular slime mold Dictyostelium discoideum.", "content": "Several lines of experimental evidence suggest that an anterior-posterior gradient of cyclic AMP exists in migrating pseudoplasmodia of the cellular slime mold Dictyostelium discoideum, and that this gradient may be responsible for control of the proportions of stalk and spore cells that form during culmination. In experiments reported here, the amounts of cyclic AMP present in the anterior and posterior portions of pseudoplasmodia were measured using a protein binding assay, and the levels obtained normalized to protein and DNA. For a variety of pseudoplasmodia migration conditions examined, the anterior portion was found to contain cyclic AMP concentrations 40 to 70% higher than the posterior portions.", "contents": "Cyclic AMP gradient in migrating pseudoplasmodia of the cellular slime mold Dictyostelium discoideum. Several lines of experimental evidence suggest that an anterior-posterior gradient of cyclic AMP exists in migrating pseudoplasmodia of the cellular slime mold Dictyostelium discoideum, and that this gradient may be responsible for control of the proportions of stalk and spore cells that form during culmination. In experiments reported here, the amounts of cyclic AMP present in the anterior and posterior portions of pseudoplasmodia were measured using a protein binding assay, and the levels obtained normalized to protein and DNA. For a variety of pseudoplasmodia migration conditions examined, the anterior portion was found to contain cyclic AMP concentrations 40 to 70% higher than the posterior portions."}
{"id": "PMID:193862", "title": "Purification and subunit composition of guanosine 3':5'-monophosphate-dependent protein kinase from bovine lung.", "content": "The guanosine 3':5'-monophosphate-dependent protein kinase from bovine lung was purified to apparent homogeneity by affinity chromography using 8-2-aminoethylthio-cGMP coupled to Sepharose 4B. The kinase activity was purified approximately 6000-fold with an overall recovery of approximately 20%. The product isolated by affinity chromatography contained both cGMP-binding and cGMP-dependent histone kinase activity, indicating that the enzyme was not dissociated into regulatory and catalytic components by the immobilized cGMP derivative. The enzyme had a molecular weight of approximately 165,000 and a sedimentation coefficient of 7.8 S. The purified kinase displayed several characteristics similar to that of the partially purified enzyme including specificity for cGMP and stimulation by high concentrations of magnesium. On sodium dodecyl sulfate gels, only one major polypeptide chain was present having a molecular weight of approximately 81,000. This subunit bound 1 mol of cGMP and exhibited cGMP-dependent protein kinase activity. It is proposed that the native enzyme consists of two identical subunits (Mr=81,000), each of which binds cGMP and catalyzes protein phosphorylation.", "contents": "Purification and subunit composition of guanosine 3':5'-monophosphate-dependent protein kinase from bovine lung. The guanosine 3':5'-monophosphate-dependent protein kinase from bovine lung was purified to apparent homogeneity by affinity chromography using 8-2-aminoethylthio-cGMP coupled to Sepharose 4B. The kinase activity was purified approximately 6000-fold with an overall recovery of approximately 20%. The product isolated by affinity chromatography contained both cGMP-binding and cGMP-dependent histone kinase activity, indicating that the enzyme was not dissociated into regulatory and catalytic components by the immobilized cGMP derivative. The enzyme had a molecular weight of approximately 165,000 and a sedimentation coefficient of 7.8 S. The purified kinase displayed several characteristics similar to that of the partially purified enzyme including specificity for cGMP and stimulation by high concentrations of magnesium. On sodium dodecyl sulfate gels, only one major polypeptide chain was present having a molecular weight of approximately 81,000. This subunit bound 1 mol of cGMP and exhibited cGMP-dependent protein kinase activity. It is proposed that the native enzyme consists of two identical subunits (Mr=81,000), each of which binds cGMP and catalyzes protein phosphorylation."}
{"id": "PMID:193863", "title": "Preparation and properties of N6-monobutyryl adenosine 5'-monophosphate. A major hepatic metabolite of N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate.", "content": "The synthesis and properties of N6-monobutyryl adenosine 5'-monophosphate are described. The properties of synthesized monobutyryl nucleotide have been compared to those of a metabolite recognized in previous studies (Castagna, M. C., Palmer, W.K., and Walsh, D.A. (1977) Arch. Biochem. Biophys. 181, 46-60) as the major radioactive product produced in the liver upon perfusion with N6,O2'-dibutyryl cyclic [3H]adenosine 3':5'-monophosphate. By the criteria of cochromatography on DEAE-cellulose and in three thin layer chromatographic systems and from equivalent rates of alkaline hydrolysis, N6-monobutyryl adenosine 5'-monophosphate has been identified as a major hepatic metabolite of N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate.", "contents": "Preparation and properties of N6-monobutyryl adenosine 5'-monophosphate. A major hepatic metabolite of N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate. The synthesis and properties of N6-monobutyryl adenosine 5'-monophosphate are described. The properties of synthesized monobutyryl nucleotide have been compared to those of a metabolite recognized in previous studies (Castagna, M. C., Palmer, W.K., and Walsh, D.A. (1977) Arch. Biochem. Biophys. 181, 46-60) as the major radioactive product produced in the liver upon perfusion with N6,O2'-dibutyryl cyclic [3H]adenosine 3':5'-monophosphate. By the criteria of cochromatography on DEAE-cellulose and in three thin layer chromatographic systems and from equivalent rates of alkaline hydrolysis, N6-monobutyryl adenosine 5'-monophosphate has been identified as a major hepatic metabolite of N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate."}
{"id": "PMID:193864", "title": "The dissociation of the surface architecture described by enhanced lectin agglutinability and the transformed phenotype expressed as anchorage independence.", "content": "Using a series of cold-sensitive variants of chemically transformed BHK-21 cells, revertants to the normal phenotype derived from a dimethyl-nitrosamine transformed clone of BHK-21 as well as revertants to the normal phenotype derived from polyoma transformed BHK-21 cells we have demonstrated that the surface phenotype described by enhanced agglutinability with Con A and WGA can be dissociated from the transformed phenotype described by anchorage independence (growth in semisolid medium). Specifically we have demonstrated that the surface characteristic of enhanced agglutinability may be found in a variety of cell lines which fail to display to grow in agar. Our work clearly shows that the two phenotypes described are not concomitantly controlled and tends to suggest that the phenotype of enhanced lectin agglutinability may be dissociated from the transformed phenotype.", "contents": "The dissociation of the surface architecture described by enhanced lectin agglutinability and the transformed phenotype expressed as anchorage independence. Using a series of cold-sensitive variants of chemically transformed BHK-21 cells, revertants to the normal phenotype derived from a dimethyl-nitrosamine transformed clone of BHK-21 as well as revertants to the normal phenotype derived from polyoma transformed BHK-21 cells we have demonstrated that the surface phenotype described by enhanced agglutinability with Con A and WGA can be dissociated from the transformed phenotype described by anchorage independence (growth in semisolid medium). Specifically we have demonstrated that the surface characteristic of enhanced agglutinability may be found in a variety of cell lines which fail to display to grow in agar. Our work clearly shows that the two phenotypes described are not concomitantly controlled and tends to suggest that the phenotype of enhanced lectin agglutinability may be dissociated from the transformed phenotype."}
{"id": "PMID:193865", "title": "Regulation of intracellular calcium in chick embryo fibroblast: calcium uptake by the microsomal fraction.", "content": "The total membrane fraction of a chick embryo fibroblast (CEF) homogenate accumulates calcium in an energy-dependent manner. This activity can be dissociated into azide-sensitive and azide-insensitive components. The azide-sensitive component of calcium uptake is believed to represent mitochondrial calcium uptake. The azide-insensitive component of calcium uptake is enhanced by the presence of a calcium trapping agent such as oxalate, and cannot utilize, ADP, inorganic phosphate and a Krebs cycle substrate to support uptake. The distribution of the azide-insensitive calcium uptake in subcellular fractions suggests that this uptake occurs in other than mitochondrial membranes. The membranes most likely to contribute to the azide-insensitive component of calcium uptake are the endoplasmic reticulum and plasma membrane. A microsomal preparation from CEF cells is essentially devoid of the azide-sensitive calcium uptake activity. This microsomal activity is similar in characteristics to the sarcoplasmic reticulum of skeletal muscle. However the specific activity of CEF microsomal calcium uptake system is much less than that found in the skeletal muscle system. The transport of calcium by these membranes provide a mechanism for the regulation of cytosol calcium levels and may play a role in the control of movement and growth of cultured cells.", "contents": "Regulation of intracellular calcium in chick embryo fibroblast: calcium uptake by the microsomal fraction. The total membrane fraction of a chick embryo fibroblast (CEF) homogenate accumulates calcium in an energy-dependent manner. This activity can be dissociated into azide-sensitive and azide-insensitive components. The azide-sensitive component of calcium uptake is believed to represent mitochondrial calcium uptake. The azide-insensitive component of calcium uptake is enhanced by the presence of a calcium trapping agent such as oxalate, and cannot utilize, ADP, inorganic phosphate and a Krebs cycle substrate to support uptake. The distribution of the azide-insensitive calcium uptake in subcellular fractions suggests that this uptake occurs in other than mitochondrial membranes. The membranes most likely to contribute to the azide-insensitive component of calcium uptake are the endoplasmic reticulum and plasma membrane. A microsomal preparation from CEF cells is essentially devoid of the azide-sensitive calcium uptake activity. This microsomal activity is similar in characteristics to the sarcoplasmic reticulum of skeletal muscle. However the specific activity of CEF microsomal calcium uptake system is much less than that found in the skeletal muscle system. The transport of calcium by these membranes provide a mechanism for the regulation of cytosol calcium levels and may play a role in the control of movement and growth of cultured cells."}
{"id": "PMID:193866", "title": "Colloidal iron hydroxide-binding to the surfaces of chick embryo fibroblasts transformed by wild-type and a temperature-sensitive mutant of Rous sarcoma virus.", "content": "The densities of colloidal iron hydroxide (CIH) particles binding to the surfaces of chick embryo fibroblasts were determined before and after transformation with wild type Rous sarcoma virus and a temperature sensitive (ts) mutant of this virus. On the basis of in vitro behavior, cells transformed by the ts virus manifest a malignant phenotype at 36 degrees C (permissive temperature) and appear normal at 41 degrees C (non-permissive temperature). At the permissive temperatures there is a significant increase in CIH particle-binding to spaces of cell surface between microvilli on the wild type and ts transformed cells. At the non-permissive temperature this significant increase in binding is only observed on the wild type transformant, while the density found on the ts transformant is not significantly different from the untransformed state. Therefore, in vitro characteristics of normalcy and malignancy are reflected in changes in the CIH binding properties of the cell surface spaces between microvilli. The CIH densities observed on the microvilli are significantly different from the density on the spaces between them for each of the classes of cells studied at either temperature. The microvilli are found to bind a lower density of particles in five of the six cases. No correlations between microvilli particle density and transformation to in vitro malignant characteristics were observed.", "contents": "Colloidal iron hydroxide-binding to the surfaces of chick embryo fibroblasts transformed by wild-type and a temperature-sensitive mutant of Rous sarcoma virus. The densities of colloidal iron hydroxide (CIH) particles binding to the surfaces of chick embryo fibroblasts were determined before and after transformation with wild type Rous sarcoma virus and a temperature sensitive (ts) mutant of this virus. On the basis of in vitro behavior, cells transformed by the ts virus manifest a malignant phenotype at 36 degrees C (permissive temperature) and appear normal at 41 degrees C (non-permissive temperature). At the permissive temperatures there is a significant increase in CIH particle-binding to spaces of cell surface between microvilli on the wild type and ts transformed cells. At the non-permissive temperature this significant increase in binding is only observed on the wild type transformant, while the density found on the ts transformant is not significantly different from the untransformed state. Therefore, in vitro characteristics of normalcy and malignancy are reflected in changes in the CIH binding properties of the cell surface spaces between microvilli. The CIH densities observed on the microvilli are significantly different from the density on the spaces between them for each of the classes of cells studied at either temperature. The microvilli are found to bind a lower density of particles in five of the six cases. No correlations between microvilli particle density and transformation to in vitro malignant characteristics were observed."}
{"id": "PMID:193870", "title": "The storage lipids in Tangier disease. A physical chemical study.", "content": "The physical states and phase behavior of the lipids of the spleen, liver, and splenic artery from a 38-yr-old man with Tangier disease were studied. Many intracellular lipid droplets in the smectic liquid crystalline state were identified by polarizing microscopy in macrophages in both the spleen and liver, but not in the splenic artery. The droplets within individual cells melted sharply over a narrow temperature range, indicating a uniform lipid composition of the droplets of each cell. However different cells melted over a wide range, 20-53 degrees C indicating heterogeneity of lipid droplet composition between cells. Furthermore, most of the cells (81%) had droplets in the liquid crystalline state at 37 degrees C. X-ray diffraction studies of splenic tissue at 37 degrees C revealed a diffraction pattern typical of cholesterol esters in the smectic liquid crystalline state. Differential scanning calorimetry of spleen showed a broad reversible transition from 29-52 degrees C, with a maximum mean transition temperature at 42 degrees C, correlating closely with the polarizing microscopy observations. The enthalpy of the transition, 0.86+/-0.07 cal/g of cholesterol ester, was quantitatively similar to that of the liquid crystalline to liquid transition of pure cholesterol esters indicating that nearly all of the cholesterol esters in the tissue were free to undergo the smectic-isotropic phase transition. Lipid compositions of spleen and liver were determined, and when plotted on the cholesterol-phospholipid-cholesterol ester phase diagram, fell within the two phase zone. The two phases, cholesterol ester droplets and phospholipid bilayers were isolated by ultracentrifugation of tissue homogenates. Lipid compositions of the separated phases approximated those predicted by the phase diagram. Extracted lipids from the spleen, when dispersed in water and ultracentrifuged, underwent phase separation in a similar way. Thus (a) most of the storage lipids in the liver and spleen of this patient were in the liquid crystalline state at body temperature, (b) the phase behavior of the storage lipids conformed to that predicted by lipid model systems indicating lipid-lipid interactions predominate in affected cells, (c) lipid droplets within individual cells have similar compositions, whereas droplet composition varies from cell to cell, and (d) cholesterol ester does not accumulate in the splenic artery. Since Tangier patients lack high density lipoprotein, we conclude that high density lipoprotein-mediated cholesterol removal from cells is essential only for those cells which have an obligate intake of cholesterol (macrophages).", "contents": "The storage lipids in Tangier disease. A physical chemical study. The physical states and phase behavior of the lipids of the spleen, liver, and splenic artery from a 38-yr-old man with Tangier disease were studied. Many intracellular lipid droplets in the smectic liquid crystalline state were identified by polarizing microscopy in macrophages in both the spleen and liver, but not in the splenic artery. The droplets within individual cells melted sharply over a narrow temperature range, indicating a uniform lipid composition of the droplets of each cell. However different cells melted over a wide range, 20-53 degrees C indicating heterogeneity of lipid droplet composition between cells. Furthermore, most of the cells (81%) had droplets in the liquid crystalline state at 37 degrees C. X-ray diffraction studies of splenic tissue at 37 degrees C revealed a diffraction pattern typical of cholesterol esters in the smectic liquid crystalline state. Differential scanning calorimetry of spleen showed a broad reversible transition from 29-52 degrees C, with a maximum mean transition temperature at 42 degrees C, correlating closely with the polarizing microscopy observations. The enthalpy of the transition, 0.86+/-0.07 cal/g of cholesterol ester, was quantitatively similar to that of the liquid crystalline to liquid transition of pure cholesterol esters indicating that nearly all of the cholesterol esters in the tissue were free to undergo the smectic-isotropic phase transition. Lipid compositions of spleen and liver were determined, and when plotted on the cholesterol-phospholipid-cholesterol ester phase diagram, fell within the two phase zone. The two phases, cholesterol ester droplets and phospholipid bilayers were isolated by ultracentrifugation of tissue homogenates. Lipid compositions of the separated phases approximated those predicted by the phase diagram. Extracted lipids from the spleen, when dispersed in water and ultracentrifuged, underwent phase separation in a similar way. Thus (a) most of the storage lipids in the liver and spleen of this patient were in the liquid crystalline state at body temperature, (b) the phase behavior of the storage lipids conformed to that predicted by lipid model systems indicating lipid-lipid interactions predominate in affected cells, (c) lipid droplets within individual cells have similar compositions, whereas droplet composition varies from cell to cell, and (d) cholesterol ester does not accumulate in the splenic artery. Since Tangier patients lack high density lipoprotein, we conclude that high density lipoprotein-mediated cholesterol removal from cells is essential only for those cells which have an obligate intake of cholesterol (macrophages)."}
{"id": "PMID:193871", "title": "Decreased H2 histamine response of granulocytes of asthmatic patients.", "content": "Increased bronchial sensitivity to inhaled histamine in asthma is well known. The mechanism of this increased bronchial sensitivity is not known nor has it been demonstrated that isolated cells respond abnormally to histamine. Polymorpho-nuclear leukocytes (PMNs) provide a homogeneous cell population to study agonist response. Release of granulocyte lysosomal enzymes is inhibited by agonists increasing the PMN cyclic AMP concentration. The release of the lysosomal enzyme beta glucuronidase by serum-activated particles of zymosan was similar in PMNs isolated from normal and asthma subjects. Histamine (100-0.01 muM) inhibited enzyme release. Except at the maximal concentration of histamine (100 muM), the response to histamine was decreased in asthma. The inhibition of enzyme release paralleled an increase in intracellular PMN cyclic AMP. In asthma, the cyclic AMP response to histamine was reduced. The H2 antihistamine metiamide blocked histamine inhibition of lysosomal enzyme release and the increase in cyclic AMP. The effect was maximal at concentrations equimolar to those of histamine. The H1 antihistamine chlorpheniramine had no effect on histamine inhibition of granulocyte lysosomal enzyme release. A decrease in the inhibition of the release of the inflammatory lysosomal enzymes from granulocytes in asthma may contribute to an enhanced bronchial inflammatory reaction.", "contents": "Decreased H2 histamine response of granulocytes of asthmatic patients. Increased bronchial sensitivity to inhaled histamine in asthma is well known. The mechanism of this increased bronchial sensitivity is not known nor has it been demonstrated that isolated cells respond abnormally to histamine. Polymorpho-nuclear leukocytes (PMNs) provide a homogeneous cell population to study agonist response. Release of granulocyte lysosomal enzymes is inhibited by agonists increasing the PMN cyclic AMP concentration. The release of the lysosomal enzyme beta glucuronidase by serum-activated particles of zymosan was similar in PMNs isolated from normal and asthma subjects. Histamine (100-0.01 muM) inhibited enzyme release. Except at the maximal concentration of histamine (100 muM), the response to histamine was decreased in asthma. The inhibition of enzyme release paralleled an increase in intracellular PMN cyclic AMP. In asthma, the cyclic AMP response to histamine was reduced. The H2 antihistamine metiamide blocked histamine inhibition of lysosomal enzyme release and the increase in cyclic AMP. The effect was maximal at concentrations equimolar to those of histamine. The H1 antihistamine chlorpheniramine had no effect on histamine inhibition of granulocyte lysosomal enzyme release. A decrease in the inhibition of the release of the inflammatory lysosomal enzymes from granulocytes in asthma may contribute to an enhanced bronchial inflammatory reaction."}
{"id": "PMID:193872", "title": "Hydrogen peroxide production in chronic granulomatous disease. A cytochemical study of reduced pyridine nucleotide oxidases.", "content": "The ability of polymorphonuclear leukocytes (PMN) to produce H(2)O(2) in response to phagocytic stimulation was examined cytochemically using leukocytes from normal individuals and patients with chronic granulomatous disease (CGD). Normal PMN oxidized diaminobenzidine within the phagocytic vacuole by a reaction dependent upon endogenous H(2)O(2) and myeloperoxidase. CGD PMN failed to oxidize diaminobenzidine, which is consistent with the biochemical data showing a lack of H(2)O(2)-generating capacity. A plasma membrane enzyme (oxidase) activated by phagocytosis is capable of H(2)O(2) production in PMN. The localization of this oxidase activity was explored in CGD PMN using a cytochemical technique specific for H(2)O(2). The enzyme activity is stimulated by exogenous NADH, but not NADPH. Reaction product formation, indicative of activity of the oxidase, is dependent upon precipitation of cerium ions by the enzymatically generated H(2)O(2). The advantage of this approach is that enzyme activity of individual cells can be assessed, allowing determination of numbers of reactive cells in the population and their relative degrees of reactivity. NADH oxidase was found to be active both on the plasma membrane and within the phagocytic vacuoles of control PMN, whereas those cells from three CGD patients showed greatly reduced activity in both these sites. Assessment of the reactivity of individual cells showed the number of cells with oxidase activity in CGD to be significantly reduced when compared to control values. Additionally, of those cells that do react, a higher percentage of them are only weakly reactive. Omission of NADH from the incubation medium reduced the percentage of control cells showing enzyme activity but had no effect on CGD PMN, implying that the enzyme is not saturated with substrate in control cells, but in CGD the diminished enzyme is fully saturated. The defect may lie in the fact that in CGD patients there are fewer cells capable of peroxide generation, and a majority of these reactive cells produce only reduced amounts of this bactericidal agent.", "contents": "Hydrogen peroxide production in chronic granulomatous disease. A cytochemical study of reduced pyridine nucleotide oxidases. The ability of polymorphonuclear leukocytes (PMN) to produce H(2)O(2) in response to phagocytic stimulation was examined cytochemically using leukocytes from normal individuals and patients with chronic granulomatous disease (CGD). Normal PMN oxidized diaminobenzidine within the phagocytic vacuole by a reaction dependent upon endogenous H(2)O(2) and myeloperoxidase. CGD PMN failed to oxidize diaminobenzidine, which is consistent with the biochemical data showing a lack of H(2)O(2)-generating capacity. A plasma membrane enzyme (oxidase) activated by phagocytosis is capable of H(2)O(2) production in PMN. The localization of this oxidase activity was explored in CGD PMN using a cytochemical technique specific for H(2)O(2). The enzyme activity is stimulated by exogenous NADH, but not NADPH. Reaction product formation, indicative of activity of the oxidase, is dependent upon precipitation of cerium ions by the enzymatically generated H(2)O(2). The advantage of this approach is that enzyme activity of individual cells can be assessed, allowing determination of numbers of reactive cells in the population and their relative degrees of reactivity. NADH oxidase was found to be active both on the plasma membrane and within the phagocytic vacuoles of control PMN, whereas those cells from three CGD patients showed greatly reduced activity in both these sites. Assessment of the reactivity of individual cells showed the number of cells with oxidase activity in CGD to be significantly reduced when compared to control values. Additionally, of those cells that do react, a higher percentage of them are only weakly reactive. Omission of NADH from the incubation medium reduced the percentage of control cells showing enzyme activity but had no effect on CGD PMN, implying that the enzyme is not saturated with substrate in control cells, but in CGD the diminished enzyme is fully saturated. The defect may lie in the fact that in CGD patients there are fewer cells capable of peroxide generation, and a majority of these reactive cells produce only reduced amounts of this bactericidal agent."}
{"id": "PMID:193873", "title": "Structural features of Salmonella typhimurium lipopolysaccharide required for activation of tissue factor in human mononuclear cells.", "content": "Activation of mononuclear cell tissue factor was examined utilizing lipopolysaccharides obtained from wild-type and both Rc and Re mutants of Salmonella typhimurium. Wild-type (smooth) lipopolysaccharide, galactose-deficient (Rc) lipopolysaccharide, heptose-deficient (Re) lipopolysaccharide, and lipid A preparations were all active in their ability to generate tissue factor activity in human mononuclear cells grown in tissue culture. Polymyxin B has been reported to prevent some of the lethal effects of endotoxin in vivo, and the drug reportedly binds to the 2-keto-3-deoxyoctulosonate-lipid A region of the lipopolysaccharide molecule. Polymyxin B was effective in inhibiting the tissue factor generating activity of wild-type lipopolysaccharide, Re lipopolysaccharide, and lipid A in a dose-dependent fashion. Treatment of lipid A preparations with mild alkali abolished the ability of these preparations to activate tissue factor in cells. Analogous to many of the other biologic properties of lipopolysaccharide, tissue factor activation in human mononuclear cells appears to depend upon the integrity of the lipid A portion of the molecule.", "contents": "Structural features of Salmonella typhimurium lipopolysaccharide required for activation of tissue factor in human mononuclear cells. Activation of mononuclear cell tissue factor was examined utilizing lipopolysaccharides obtained from wild-type and both Rc and Re mutants of Salmonella typhimurium. Wild-type (smooth) lipopolysaccharide, galactose-deficient (Rc) lipopolysaccharide, heptose-deficient (Re) lipopolysaccharide, and lipid A preparations were all active in their ability to generate tissue factor activity in human mononuclear cells grown in tissue culture. Polymyxin B has been reported to prevent some of the lethal effects of endotoxin in vivo, and the drug reportedly binds to the 2-keto-3-deoxyoctulosonate-lipid A region of the lipopolysaccharide molecule. Polymyxin B was effective in inhibiting the tissue factor generating activity of wild-type lipopolysaccharide, Re lipopolysaccharide, and lipid A in a dose-dependent fashion. Treatment of lipid A preparations with mild alkali abolished the ability of these preparations to activate tissue factor in cells. Analogous to many of the other biologic properties of lipopolysaccharide, tissue factor activation in human mononuclear cells appears to depend upon the integrity of the lipid A portion of the molecule."}
{"id": "PMID:193874", "title": "Overloading human aortic smooth muscle cells with low density lipoprotein-cholesteryl esters reproduces features of atherosclerosis in vitro.", "content": "Human aortic smooth muscle cells accumulate only small amounts of cholesteryl esters in tissue culture, even when incubated for prolonged periods with high levels of plasma low density lipoprotein (LDL). This failure to overaccumulate LDL-cholesteryl esters is due to an LDL-mediated feedback suppression of the activity of the cell surface LDL receptor, a regulatory action that limits the rate at which the cells take up LDL. This regulatory system can be bypassed by incubating smooth muscle cells with LDL that has been given a strong positive charge by covalent linkage with N,N-dimethyl-1,3-propanediamine (DMPA-LDL). The unregulated uptake of DMPA-LDL produces a massive deposition of cholesteryl esters in the form of inclusions within the cell. These inclusions take up lipid stains and exhibit positive birefringence with form\u00e9e crosses that are typical of liquid crystals of cholesteryl esters. By electron microscopy, the cholesteryl ester inclusions appear as homogeneous gray cytoplasmic lipid droplets. The current studies demonstrate that the unregulated uptake of LDL-cholesteryl esters by human aortic smooth muscle cells can reproduce in vitro the major biochemical and morphological alterations that occur within smooth muscle cells in vivo during the process of atherosclerosis.", "contents": "Overloading human aortic smooth muscle cells with low density lipoprotein-cholesteryl esters reproduces features of atherosclerosis in vitro. Human aortic smooth muscle cells accumulate only small amounts of cholesteryl esters in tissue culture, even when incubated for prolonged periods with high levels of plasma low density lipoprotein (LDL). This failure to overaccumulate LDL-cholesteryl esters is due to an LDL-mediated feedback suppression of the activity of the cell surface LDL receptor, a regulatory action that limits the rate at which the cells take up LDL. This regulatory system can be bypassed by incubating smooth muscle cells with LDL that has been given a strong positive charge by covalent linkage with N,N-dimethyl-1,3-propanediamine (DMPA-LDL). The unregulated uptake of DMPA-LDL produces a massive deposition of cholesteryl esters in the form of inclusions within the cell. These inclusions take up lipid stains and exhibit positive birefringence with form\u00e9e crosses that are typical of liquid crystals of cholesteryl esters. By electron microscopy, the cholesteryl ester inclusions appear as homogeneous gray cytoplasmic lipid droplets. The current studies demonstrate that the unregulated uptake of LDL-cholesteryl esters by human aortic smooth muscle cells can reproduce in vitro the major biochemical and morphological alterations that occur within smooth muscle cells in vivo during the process of atherosclerosis."}
{"id": "PMID:193876", "title": "Polybrominated biphenyls in raw milk and processed dairy products.", "content": "Milk from four dairy herds identified by the Michigan Department of Agriculture as containing less than .3 ppm (fat basis) physiologically incorporated polybrominated biphenyls was processed individually into cream, skim milk, butter, and stirred curd cheese. Pasteurized and freeze-dried whole milk, skim milk, and cream, spray-dried whole milk and skim milk, and condensed whole milk were made also. Polybrominated biphenyls were concentrated in the high-fat products. Pasteurized skim milk, buttermilk, and whey had slightly more polybrominated biphenyls than pasteurized whole milk on a fat basis. Spray-drying reduced the polybrominated biphenyls in whole milk and skim milk while pasteurization, freeze-drying, aging of cheese, and condensation were not effective.", "contents": "Polybrominated biphenyls in raw milk and processed dairy products. Milk from four dairy herds identified by the Michigan Department of Agriculture as containing less than .3 ppm (fat basis) physiologically incorporated polybrominated biphenyls was processed individually into cream, skim milk, butter, and stirred curd cheese. Pasteurized and freeze-dried whole milk, skim milk, and cream, spray-dried whole milk and skim milk, and condensed whole milk were made also. Polybrominated biphenyls were concentrated in the high-fat products. Pasteurized skim milk, buttermilk, and whey had slightly more polybrominated biphenyls than pasteurized whole milk on a fat basis. Spray-drying reduced the polybrominated biphenyls in whole milk and skim milk while pasteurization, freeze-drying, aging of cheese, and condensation were not effective."}
{"id": "PMID:193878", "title": "Shock and the kidney: pathophysiology and pharmacological support.", "content": "This article reviews current knowledge as to the physiological mechanisms that control renal vascular resistence. The contribution of both extrinsic and intrinsic neuro-humoral regulation of both blood flow and glomerular filtration rate are described. The changes that occur both to the renal blood flow and glomerular filtration rate in the pathophysiological situation of \"pre-renal uraemia\" as well as \"acute tubular necrosis\" are described. Within this setting pharmacological manoeuvres that may improve both renal blood flow and glomerular filtration rate are discussed. In addition, the indications for and general principles of haemo-and peritoneal dialysis are described.", "contents": "Shock and the kidney: pathophysiology and pharmacological support. This article reviews current knowledge as to the physiological mechanisms that control renal vascular resistence. The contribution of both extrinsic and intrinsic neuro-humoral regulation of both blood flow and glomerular filtration rate are described. The changes that occur both to the renal blood flow and glomerular filtration rate in the pathophysiological situation of \"pre-renal uraemia\" as well as \"acute tubular necrosis\" are described. Within this setting pharmacological manoeuvres that may improve both renal blood flow and glomerular filtration rate are discussed. In addition, the indications for and general principles of haemo-and peritoneal dialysis are described."}
{"id": "PMID:193987", "title": "Target cells for interferon production in human leukocytes stimulated by sendai virus.", "content": "Whole leukocytes, mononuclear cells, polymorphonuclear cells (PMN), MONOCYTES, PURIFIED LYMPHOCYTES, AND T (rosette-forming cells, RFC) and non-T (nonrosette-forming cells, nonRFC) lymphocytes isolated from the human peripheral blood were stimulated by Sendai virus, respectively, and examined for interferon production in their culture fluids. High levels of interferon were produced by mononuclear cells, but not by PMN. Removal of monocytes from the mononuclear cell population did not affect at all the levels of interferon produced, although it strongly suppressed interferon induction by polyinosinic-polycytidylic acid (poly IC) and mitogenic response to phytohemagglutinin (PHA) of the lymphocytes. Purified monocytes and T lymphocytes were unresponsive to the virus. In contrast, a population of purified non-T lymphocytes produced high levels of interferon. Addition of monocytes to the interferon-producing non-T lymphocytes did not affect the levels of interferon produced. No detectable levels of interferon were produced in the mixture of T lymphocytes and monocytes. It is concluded that non-T lymphocytes may be a major target for interferon induction of human leukocytes by Sendai virus.", "contents": "Target cells for interferon production in human leukocytes stimulated by sendai virus. Whole leukocytes, mononuclear cells, polymorphonuclear cells (PMN), MONOCYTES, PURIFIED LYMPHOCYTES, AND T (rosette-forming cells, RFC) and non-T (nonrosette-forming cells, nonRFC) lymphocytes isolated from the human peripheral blood were stimulated by Sendai virus, respectively, and examined for interferon production in their culture fluids. High levels of interferon were produced by mononuclear cells, but not by PMN. Removal of monocytes from the mononuclear cell population did not affect at all the levels of interferon produced, although it strongly suppressed interferon induction by polyinosinic-polycytidylic acid (poly IC) and mitogenic response to phytohemagglutinin (PHA) of the lymphocytes. Purified monocytes and T lymphocytes were unresponsive to the virus. In contrast, a population of purified non-T lymphocytes produced high levels of interferon. Addition of monocytes to the interferon-producing non-T lymphocytes did not affect the levels of interferon produced. No detectable levels of interferon were produced in the mixture of T lymphocytes and monocytes. It is concluded that non-T lymphocytes may be a major target for interferon induction of human leukocytes by Sendai virus."}
{"id": "PMID:193988", "title": "Somatic cell hybrids between mouse peritoneal macrophages and SV40-transformed human cells. III. Identification of surface antigens coded for by human chromosomes 7 and 17.", "content": "Somatic cell hybrids between SV40-transformed human cell lines and mouse peritoneal macrophages (MPM) containing either human chromosome 7 or 17 carrying the SV40 genome were injected into mice syngeneic to the mouse parental cells. Since either chromosome 7 or 17 was the only human chromosome present in the hybrids used as immunogens, the humoral immune response to gene products coded for by either chromosome was assayed. Using a sensitive radioimmunoassay, we were able to identify noncross-reactive cell-surface antigen(s) specifically coded for by either human chromosome 7 or 17, and present in normal, tumor-derived and virus-transformed human cells. However, no reactivity against SV40 tumor-specific surface antigen (TSSA) could be detected in the antisera.", "contents": "Somatic cell hybrids between mouse peritoneal macrophages and SV40-transformed human cells. III. Identification of surface antigens coded for by human chromosomes 7 and 17. Somatic cell hybrids between SV40-transformed human cell lines and mouse peritoneal macrophages (MPM) containing either human chromosome 7 or 17 carrying the SV40 genome were injected into mice syngeneic to the mouse parental cells. Since either chromosome 7 or 17 was the only human chromosome present in the hybrids used as immunogens, the humoral immune response to gene products coded for by either chromosome was assayed. Using a sensitive radioimmunoassay, we were able to identify noncross-reactive cell-surface antigen(s) specifically coded for by either human chromosome 7 or 17, and present in normal, tumor-derived and virus-transformed human cells. However, no reactivity against SV40 tumor-specific surface antigen (TSSA) could be detected in the antisera."}
{"id": "PMID:193989", "title": "The role of neutrophils in antiviral defense--in vitro studies on the mechanism of antiviral inhibition.", "content": "Highly enriched populations of bovine neutrophils were added, in the presence of antiviral antibody, to herpesvirus-infected bovine cell cultures. A cell dose-dependent reduction in virus-induced cytopathology was observed. The mechanism of inhibition was presumed to be mediated by a subcellular neutrophil product and not the result of either direct cytotoxicity or antibody-dependent cell-mediated cytotoxicity (ADCC). Thus, inhibition of comparable magnitude was observed when neutrophils and virus-infected cells were separated by cell impermeable membranes. In addition, plaque reduction occurred when antiviral immunoglobulins or fragments unable to mediate ADCC were used in the assays. Killed neutrophils and sonicates were unable to mediate plaque inhibition. Speculations were made as to the origin of the virus-inhibitory substances and the role that neutrophils might assume in mediating recovery from virus infection.", "contents": "The role of neutrophils in antiviral defense--in vitro studies on the mechanism of antiviral inhibition. Highly enriched populations of bovine neutrophils were added, in the presence of antiviral antibody, to herpesvirus-infected bovine cell cultures. A cell dose-dependent reduction in virus-induced cytopathology was observed. The mechanism of inhibition was presumed to be mediated by a subcellular neutrophil product and not the result of either direct cytotoxicity or antibody-dependent cell-mediated cytotoxicity (ADCC). Thus, inhibition of comparable magnitude was observed when neutrophils and virus-infected cells were separated by cell impermeable membranes. In addition, plaque reduction occurred when antiviral immunoglobulins or fragments unable to mediate ADCC were used in the assays. Killed neutrophils and sonicates were unable to mediate plaque inhibition. Speculations were made as to the origin of the virus-inhibitory substances and the role that neutrophils might assume in mediating recovery from virus infection."}
{"id": "PMID:193990", "title": "Effect of LDL-In, a normal immunoregulatory human serum low density lipoprotein, on the interaction of macrophages with lymphocytes proliferating in response to mitogen and allogeneic stimulation.", "content": "The immunoregulatory properties of LDL-In, a normal species of human serum low density lipoprotein which suppresses indictive events involved in triggering of lymphoid cells by lectins and antigens, were analyzed in order to distinguish between a primary effect on macrophages and lymphocytes. LDL-In was found to be equally effective in suppression of the response of human lymphocytes to tpha at concentrations of lectin demonstrated to impart apparent macrophage-independence or macrophage-dependence to the culture system. Exposure of only the macrophages to LDL-In was shown to be without effect on subsequent in vitro lymphocyte responses to either PHA or allogeneic cells, whereas exposure of only the lymphocytes to LDL-In was fully effective. The cellular locus was further identified by demonstrating that the responder lymphocytes, but not the stimulator lymphocytes, were the target of the suppressive activity in mixed lymphocyte reactions. These data considered in conjunction with previous studies suggest that the primary untriggered lymphocyte is the most probable cellular target for the bioregulatory effects of LDL-In.", "contents": "Effect of LDL-In, a normal immunoregulatory human serum low density lipoprotein, on the interaction of macrophages with lymphocytes proliferating in response to mitogen and allogeneic stimulation. The immunoregulatory properties of LDL-In, a normal species of human serum low density lipoprotein which suppresses indictive events involved in triggering of lymphoid cells by lectins and antigens, were analyzed in order to distinguish between a primary effect on macrophages and lymphocytes. LDL-In was found to be equally effective in suppression of the response of human lymphocytes to tpha at concentrations of lectin demonstrated to impart apparent macrophage-independence or macrophage-dependence to the culture system. Exposure of only the macrophages to LDL-In was shown to be without effect on subsequent in vitro lymphocyte responses to either PHA or allogeneic cells, whereas exposure of only the lymphocytes to LDL-In was fully effective. The cellular locus was further identified by demonstrating that the responder lymphocytes, but not the stimulator lymphocytes, were the target of the suppressive activity in mixed lymphocyte reactions. These data considered in conjunction with previous studies suggest that the primary untriggered lymphocyte is the most probable cellular target for the bioregulatory effects of LDL-In."}
{"id": "PMID:193992", "title": "The elimination of herpes simplex plaques by antibody and the emergence of resistant strains.", "content": "Established type 1 HSV plaques were eliminated by antibody. Antibody had to remain in contact with infected cells for several days to have a maxi;mum effect. It did not prevent the production of viral induced antigens in a cell when applied after the cell was infected but did prevent the transmission of infection to contiguous cells. Strains which were resistant to elimination by antibody formed syncytia, did not grow to significantly higher titers than nonresistant strains, and were as easily neutralized by antiserum as nonresistant strains.", "contents": "The elimination of herpes simplex plaques by antibody and the emergence of resistant strains. Established type 1 HSV plaques were eliminated by antibody. Antibody had to remain in contact with infected cells for several days to have a maxi;mum effect. It did not prevent the production of viral induced antigens in a cell when applied after the cell was infected but did prevent the transmission of infection to contiguous cells. Strains which were resistant to elimination by antibody formed syncytia, did not grow to significantly higher titers than nonresistant strains, and were as easily neutralized by antiserum as nonresistant strains."}
{"id": "PMID:193993", "title": "Antibody-dependent, eosinophil-mediated damage to 51Cr-labeled schistosomula of Schistosoma mansoni: effect of metabolic inhibitors and other agents which alter cell function.", "content": "The effect of drugs known to inhibit different metabolic pathways or cell functions on antibody-dependent, eosinophil-mediated damage to schistosomula was determined. Eosinophil-mediated damage was completely inhibited by cytochalasin B, inhibitors of glycolysis, aminophylline, and treatment of cells with diazotized sulfanilic acid and tosyl-lysyl-chloromethyl ketone. The effects of cytochalasin and 2-deoxyglucose were reversible. On the other hand, eosinophil-mediated damage was unaffected by agents which inhibit DNA replication, protein synthesis, oxidative respiration, prostaglandin synthesis, and microtubule aggregation. The findings suggest that alteration of the cell surface membrane and microfilaments prevents damage by interfering with cell-target interactions, that energy derived from glycolysis is required for cytotoxicity, that cell-associated esterases are probably involved, and that cytotoxicity may be modulated by cyclic nucleotides. Some of the attributes of eosinophils that allow it and not other cells to mediate this reaction are discussed.", "contents": "Antibody-dependent, eosinophil-mediated damage to 51Cr-labeled schistosomula of Schistosoma mansoni: effect of metabolic inhibitors and other agents which alter cell function. The effect of drugs known to inhibit different metabolic pathways or cell functions on antibody-dependent, eosinophil-mediated damage to schistosomula was determined. Eosinophil-mediated damage was completely inhibited by cytochalasin B, inhibitors of glycolysis, aminophylline, and treatment of cells with diazotized sulfanilic acid and tosyl-lysyl-chloromethyl ketone. The effects of cytochalasin and 2-deoxyglucose were reversible. On the other hand, eosinophil-mediated damage was unaffected by agents which inhibit DNA replication, protein synthesis, oxidative respiration, prostaglandin synthesis, and microtubule aggregation. The findings suggest that alteration of the cell surface membrane and microfilaments prevents damage by interfering with cell-target interactions, that energy derived from glycolysis is required for cytotoxicity, that cell-associated esterases are probably involved, and that cytotoxicity may be modulated by cyclic nucleotides. Some of the attributes of eosinophils that allow it and not other cells to mediate this reaction are discussed."}
{"id": "PMID:193994", "title": "Development of cellular anti-tumor immunity in chickens bearing tumors induced by Rous sarcoma virus.", "content": "The technique of peripheral lymphocyte stimulation in response to antigen was used to demonstrate the existence of cell-mediated anti-tumor immunity in chickens bearing tumors induced by avian sarcoma viruses. The expression of this anti-tumor response against virus-containing transformed cell culture supernatant fluids and cell extracts varied among animals in terms of time after inoculation with the oncogenic agent. Animals whose tumors had completely regressed rapidly lost the ability to mount such continuing immunity. In addition, we found evidence that some normal animals express endogenous levels of natural immunity against neoplasms induced by these viruses and/or against the viruses themselves.", "contents": "Development of cellular anti-tumor immunity in chickens bearing tumors induced by Rous sarcoma virus. The technique of peripheral lymphocyte stimulation in response to antigen was used to demonstrate the existence of cell-mediated anti-tumor immunity in chickens bearing tumors induced by avian sarcoma viruses. The expression of this anti-tumor response against virus-containing transformed cell culture supernatant fluids and cell extracts varied among animals in terms of time after inoculation with the oncogenic agent. Animals whose tumors had completely regressed rapidly lost the ability to mount such continuing immunity. In addition, we found evidence that some normal animals express endogenous levels of natural immunity against neoplasms induced by these viruses and/or against the viruses themselves."}
{"id": "PMID:193995", "title": "In vitro primary induction of cytotoxic T cells against virus-infected syngeneic cells.", "content": "An in vitro method is described for primary induction of murine cytotoxic T cells against syngeneic cells infected with ectromelia or lymphocytic choriomeningitis (LCM) virus. Cytotoxicity was assayed by 51Cr release from macrophage or L929 target cells. Cytotoxic activity was sensitive to anti-theta and complement and was expressed only against target cells infected with the same virus and sharing H-2K or H-2D genes with the infected stimulator cells. The crucial factors in generating responses were mouse strain, responder: stimulator ratio, nature of infected stimulator cells, and presence of sufficient macrophages. C57BL/6 cells were less demanding than CBA/H and BALB/c cells. Under optimal conditions defined here, the in vitro response had similar kinetics and potency to the primary response in the spleen in vivo.", "contents": "In vitro primary induction of cytotoxic T cells against virus-infected syngeneic cells. An in vitro method is described for primary induction of murine cytotoxic T cells against syngeneic cells infected with ectromelia or lymphocytic choriomeningitis (LCM) virus. Cytotoxicity was assayed by 51Cr release from macrophage or L929 target cells. Cytotoxic activity was sensitive to anti-theta and complement and was expressed only against target cells infected with the same virus and sharing H-2K or H-2D genes with the infected stimulator cells. The crucial factors in generating responses were mouse strain, responder: stimulator ratio, nature of infected stimulator cells, and presence of sufficient macrophages. C57BL/6 cells were less demanding than CBA/H and BALB/c cells. Under optimal conditions defined here, the in vitro response had similar kinetics and potency to the primary response in the spleen in vivo."}
{"id": "PMID:193997", "title": "Immune adherence hemagglutination: further observations on demonstration of antibody to varicella-zoster virus.", "content": "The immune adherence hemagglutination test for measurement of antibody to varicella-zoster (V-Z) virus is well suited to performance in a routine serology laboratory. This test is useful in assessing susceptibility to varicella, measuring antibody to V-Z virus in  globulin preparations, and evaluating some effects of passive immunization. Since the complement-fixation test for antibody to V-Z virus lacks sensitivity and the fluorescent antibody to membrane antigen test is not readily available, the immune adherence hemagglutination test may be of practical value in patient management.", "contents": "Immune adherence hemagglutination: further observations on demonstration of antibody to varicella-zoster virus. The immune adherence hemagglutination test for measurement of antibody to varicella-zoster (V-Z) virus is well suited to performance in a routine serology laboratory. This test is useful in assessing susceptibility to varicella, measuring antibody to V-Z virus in  globulin preparations, and evaluating some effects of passive immunization. Since the complement-fixation test for antibody to V-Z virus lacks sensitivity and the fluorescent antibody to membrane antigen test is not readily available, the immune adherence hemagglutination test may be of practical value in patient management."}
{"id": "PMID:193998", "title": "Synergistic infection with murine cytomegalovirus and Candida albicans in mice.", "content": "A previous report from this laboratory demonstrated that mice infected intraperitoneally with a 20% lethal inoculation of murine cytomegalovirus (CMV) exhibited markedly enhanced mortality rates (80%-100%) after an intravenous injection of a 0-20% lethal inoculum of Candida albicans. The current study revealed that mice infected with murine CMV alone had high titers of virus in spleen, liver, lung, and kidney from days 3 through 20, whereas those inoculated with C. albicans alone had a self-limited fungal infection involving only the kidney. In the combined murine CMV-C. albicans infection, the titers of murine CMV in tissues were changed very little. In contrast, C. albicans was recovered from multiple organs, and a progressive renal infection developed. This altered pathogenesis of the candida infection in murine CMV-infected mice resembled that produced by a 100% lethal inoculum of C. albicans alone. These results indicate that the murine CMV infection enhanced the susceptibility of mice to infection with C. albicans and suggest that death was due to progressive fungal infection of the kidney.", "contents": "Synergistic infection with murine cytomegalovirus and Candida albicans in mice. A previous report from this laboratory demonstrated that mice infected intraperitoneally with a 20% lethal inoculation of murine cytomegalovirus (CMV) exhibited markedly enhanced mortality rates (80%-100%) after an intravenous injection of a 0-20% lethal inoculum of Candida albicans. The current study revealed that mice infected with murine CMV alone had high titers of virus in spleen, liver, lung, and kidney from days 3 through 20, whereas those inoculated with C. albicans alone had a self-limited fungal infection involving only the kidney. In the combined murine CMV-C. albicans infection, the titers of murine CMV in tissues were changed very little. In contrast, C. albicans was recovered from multiple organs, and a progressive renal infection developed. This altered pathogenesis of the candida infection in murine CMV-infected mice resembled that produced by a 100% lethal inoculum of C. albicans alone. These results indicate that the murine CMV infection enhanced the susceptibility of mice to infection with C. albicans and suggest that death was due to progressive fungal infection of the kidney."}
{"id": "PMID:193999", "title": "Fecal excretion of hepatitis A virus in humans.", "content": "To define more completely the period of fecal excretion of virus during hepatitis A virus infection, we studied 24 fecal samples from six children with clinical illness during an epidemic of type A hepatitis. As determined by immune electron microscopy, the six patients had detectable viral excretion before or by the time of the first abnormality in serum glutamic-pyruvic transaminase (alanine aminotransferase). Viral excretion reached a peak early and declined to undetectable levels before levels of serum enzyme reached a peak. These data accord with epidemiologic evidence that the person who already has symptoms and signs of type A hepatitis is unlikely to transmit the infection to others. Immune electron microscopy, therefore, may be a better index to the period of communicability than studies of experimental infection in human subjects. This conclusion would imply that precautions against fecal contamination are not usually necessary for patients hospitalized with type A hepatitis.", "contents": "Fecal excretion of hepatitis A virus in humans. To define more completely the period of fecal excretion of virus during hepatitis A virus infection, we studied 24 fecal samples from six children with clinical illness during an epidemic of type A hepatitis. As determined by immune electron microscopy, the six patients had detectable viral excretion before or by the time of the first abnormality in serum glutamic-pyruvic transaminase (alanine aminotransferase). Viral excretion reached a peak early and declined to undetectable levels before levels of serum enzyme reached a peak. These data accord with epidemiologic evidence that the person who already has symptoms and signs of type A hepatitis is unlikely to transmit the infection to others. Immune electron microscopy, therefore, may be a better index to the period of communicability than studies of experimental infection in human subjects. This conclusion would imply that precautions against fecal contamination are not usually necessary for patients hospitalized with type A hepatitis."}
{"id": "PMID:194000", "title": "Inhibition of simian virus 40-induced tumors by antisera to fetal hamster tissue.", "content": "Growth of tumors induced in hamsters with simian virus 40 (SV40) or SV40-transformed cells was inhibited by antisera to fetal hamster thymocytes or liver. This result was in contrast to the enhancement of tumor growth by antisera to adult hamster thymocytes.", "contents": "Inhibition of simian virus 40-induced tumors by antisera to fetal hamster tissue. Growth of tumors induced in hamsters with simian virus 40 (SV40) or SV40-transformed cells was inhibited by antisera to fetal hamster thymocytes or liver. This result was in contrast to the enhancement of tumor growth by antisera to adult hamster thymocytes."}
{"id": "PMID:194005", "title": "The effect of sodium azide on the chemiluminescence of granulocytes--evidence for the generation of multiple oxygen radicals.", "content": "It has been established that granulocytes generate superoxide (O-2) as well as hydrogen peroxide (H2O2) during phagocytosis. The chemiluminescence (CL) generated by phagocytes appears dependent on these oxygen radicals (or). however, recent studies suggest that oxygen molecules, including singlet oxygen (1O2) or hydroxyl radicals (OH-), may also be generated during phagocytosis and contribute to CL. We have tested this possibility by studying human granulocyte CL in the presence of 0.1 mM sodium azide, a known inhibitor of myeloperoxidase and catalase and a scavenger of 1O2. The effects of azide on CL were correlated with the effects of this compound on hexose monophosphate shunt (hmps) activity, nitroblue tetrazolium (NBT) dye reduction, formate oxidation, and cytochrome c reduction. CL generated by granulocytes during the phagocytosis of zymosan particles was markedly impaired by azide (24% to 47% of control values). On the other hand, phenomena dependent in part on the presence of O2 radicals, i.e., reduction of NBT dye and cytochrome c, were not impaired by the presence of azide. As would be expected, inhibition of catalase by azide virtually abolished the oxidation of formate, but the burst in HMPS activity associated with phagocytosis was augmented further. The latter observation indicated that azide did not impair generation of H2O2 but increased the relative amount detoxified via the HMPS. The experiment provides evidence that radicals other than O-2 and H2O2 are generated during phagocytosis and that these radicals are major contributors to the CL phenomenon.", "contents": "The effect of sodium azide on the chemiluminescence of granulocytes--evidence for the generation of multiple oxygen radicals. It has been established that granulocytes generate superoxide (O-2) as well as hydrogen peroxide (H2O2) during phagocytosis. The chemiluminescence (CL) generated by phagocytes appears dependent on these oxygen radicals (or). however, recent studies suggest that oxygen molecules, including singlet oxygen (1O2) or hydroxyl radicals (OH-), may also be generated during phagocytosis and contribute to CL. We have tested this possibility by studying human granulocyte CL in the presence of 0.1 mM sodium azide, a known inhibitor of myeloperoxidase and catalase and a scavenger of 1O2. The effects of azide on CL were correlated with the effects of this compound on hexose monophosphate shunt (hmps) activity, nitroblue tetrazolium (NBT) dye reduction, formate oxidation, and cytochrome c reduction. CL generated by granulocytes during the phagocytosis of zymosan particles was markedly impaired by azide (24% to 47% of control values). On the other hand, phenomena dependent in part on the presence of O2 radicals, i.e., reduction of NBT dye and cytochrome c, were not impaired by the presence of azide. As would be expected, inhibition of catalase by azide virtually abolished the oxidation of formate, but the burst in HMPS activity associated with phagocytosis was augmented further. The latter observation indicated that azide did not impair generation of H2O2 but increased the relative amount detoxified via the HMPS. The experiment provides evidence that radicals other than O-2 and H2O2 are generated during phagocytosis and that these radicals are major contributors to the CL phenomenon."}
{"id": "PMID:194006", "title": "Automated microdensitometry and quantification of lipoproteins by agarose gel electrophoresis.", "content": "A major obstacle in the application of quantitative microelectrophoresis has been tedious manipulations and calculations. To overcome these difficulties, we have developed an automatic system for the microdensitometry and calculations as part of a quantitative agarose gel electrophoresis facility. Results are internally standardized by serum cholesterol and/or triglyceride measurements. The hardware consists of a densitometer, an analog to digital converter, a cathode ray tube terminal, a teleprinter, and a small computer. A program in 4K words allows sample coding, electrophoretic scan display, indexing, and systematic identification of each peak. Data are acquired from scans of electrophoretic patterns of serum alone or in combination with the 1.006 gm/ml VLDL top and/or bottom preparative lipoprotein fractions. As many as 30 scans can be stored in 4K words of memory and then sent via high-speed telephone line to a larger computer for remote processing. The analysis corrects for baseline drifts and pre-beta asymmetry and will properly identify and quantify the amount of VLDL, LDL, and HDL with corrections for \"sinking pre-beta\" and \"floating beta\" in LDL and VLDL, respectively. Results are given in milligrams per 100 milliliter as well as percentile rank and standard deviation score ranking of each lipoprotein class as compared to an appropriate normal reference population. The latter data are in a form more meaningful to the physician and patient and provide a quantitative dimension to lipoprotein phenotyping.", "contents": "Automated microdensitometry and quantification of lipoproteins by agarose gel electrophoresis. A major obstacle in the application of quantitative microelectrophoresis has been tedious manipulations and calculations. To overcome these difficulties, we have developed an automatic system for the microdensitometry and calculations as part of a quantitative agarose gel electrophoresis facility. Results are internally standardized by serum cholesterol and/or triglyceride measurements. The hardware consists of a densitometer, an analog to digital converter, a cathode ray tube terminal, a teleprinter, and a small computer. A program in 4K words allows sample coding, electrophoretic scan display, indexing, and systematic identification of each peak. Data are acquired from scans of electrophoretic patterns of serum alone or in combination with the 1.006 gm/ml VLDL top and/or bottom preparative lipoprotein fractions. As many as 30 scans can be stored in 4K words of memory and then sent via high-speed telephone line to a larger computer for remote processing. The analysis corrects for baseline drifts and pre-beta asymmetry and will properly identify and quantify the amount of VLDL, LDL, and HDL with corrections for \"sinking pre-beta\" and \"floating beta\" in LDL and VLDL, respectively. Results are given in milligrams per 100 milliliter as well as percentile rank and standard deviation score ranking of each lipoprotein class as compared to an appropriate normal reference population. The latter data are in a form more meaningful to the physician and patient and provide a quantitative dimension to lipoprotein phenotyping."}
{"id": "PMID:194007", "title": "The lecithin-cholesterol acyl transferase activity of rat intestinal lymph.", "content": "The lecithin-cholesterol acyl transferase (LCAT) activity in rat mesenteric lymph was examined as a possible source of chylomicron cholesteryl ester. Lymph activity was only 2-3% of rat serum activity. Removal of d less than 1.006 lipoproteins increased lymph LCAT activity, but only to 6-8% of that of serum. Relative to total cholesterol in the d greater than 1.08 g/ml fractions, lymph LCAT activity in lymph from fasting rats was less than serum, but in lymph from nonfasting rats the ratio LCAT/HDL-cholesterol reached levels greater than serum, suggesting a contribution of enzyme from the gut. Both LCAT activity and HDL concentration in mesenteric lymph increased during feeding. Subfractions of lymph that inhibited serum LCAT were: chylomicrons, VLDL, chylomicron lipid, VLDL apoprotein, and HDL apoprotein. In the rat, the low LCAT activity of mesenteric lymph was in part due to the low enzyme concentration present, and the activity was apparently lowered further by lipid-rich lipoproteins that inhibited the reaction. Enzyme inhibition due to the apoprotein fractions of lipoproteins is probably minor in the rat in vivo.", "contents": "The lecithin-cholesterol acyl transferase activity of rat intestinal lymph. The lecithin-cholesterol acyl transferase (LCAT) activity in rat mesenteric lymph was examined as a possible source of chylomicron cholesteryl ester. Lymph activity was only 2-3% of rat serum activity. Removal of d less than 1.006 lipoproteins increased lymph LCAT activity, but only to 6-8% of that of serum. Relative to total cholesterol in the d greater than 1.08 g/ml fractions, lymph LCAT activity in lymph from fasting rats was less than serum, but in lymph from nonfasting rats the ratio LCAT/HDL-cholesterol reached levels greater than serum, suggesting a contribution of enzyme from the gut. Both LCAT activity and HDL concentration in mesenteric lymph increased during feeding. Subfractions of lymph that inhibited serum LCAT were: chylomicrons, VLDL, chylomicron lipid, VLDL apoprotein, and HDL apoprotein. In the rat, the low LCAT activity of mesenteric lymph was in part due to the low enzyme concentration present, and the activity was apparently lowered further by lipid-rich lipoproteins that inhibited the reaction. Enzyme inhibition due to the apoprotein fractions of lipoproteins is probably minor in the rat in vivo."}
{"id": "PMID:194008", "title": "Alterations of the plasma lipoproteins and apoproteins following cholesterol feeding in the rat.", "content": "The feeding of cholesterol to rats resulted in marked alterations in the type and distribution of the plasma lipoproteins and their apoproteins. The hyperlipoproteinemia was characterized by an increase in the d < 1.006 lipoproteins (B-VLDL and VLDL), an increase in the intermediate and low density lipoproteins (LDL), and the appearance of HDL(c). Associated with these lipoproteins was a prominence of the arginine-rich apoprotein. The high density lipoproteins (HDL) were decreased. A two-dimensional immunoelectrophoretic procedure was adapted to quantitate the changes in distribution of the arginine-rich apoprotein in the plasma and various ultracentrifugal fractions obtained from control and cholesterol-fed rats. In rats fed the cholesterol diet, the total plasma arginine-rich apoprotein increased from a control value of approximately 29 mg/dl to 47 mg/dl. The method of ultracentrifugation, however, was found to markedly alter the quantitative results. When the 60 Ti rotor was used at maximum speed to isolate the ultracentrifugal fractions, less than 50% of the total plasma arginine-rich apoprotein was associated with the lipoproteins in the d < 1.006 or the d 1.006-1.02, 1.02-1.063, or 1.063-1.21 ultracentrifugal fractions. By contrast, after limited ultracentrifugation with the 40 rotor, much less arginine-rich apoprotein was lost, with approximately 20% of the arginine-rich apoprotein in control rats and 10% in cholesterol-fed rats found in the d > 1.21 fraction. Significant alterations in the arginine-rich apoprotein quantitation notwithstanding, the observations of increased arginine-rich apoprotein in the B-VLDL, intermediate fraction, and HDL(c) following cholesterol feeding remained valid. However, precise quantitation awaits refinements in lipoprotein isolation techniques.", "contents": "Alterations of the plasma lipoproteins and apoproteins following cholesterol feeding in the rat. The feeding of cholesterol to rats resulted in marked alterations in the type and distribution of the plasma lipoproteins and their apoproteins. The hyperlipoproteinemia was characterized by an increase in the d < 1.006 lipoproteins (B-VLDL and VLDL), an increase in the intermediate and low density lipoproteins (LDL), and the appearance of HDL(c). Associated with these lipoproteins was a prominence of the arginine-rich apoprotein. The high density lipoproteins (HDL) were decreased. A two-dimensional immunoelectrophoretic procedure was adapted to quantitate the changes in distribution of the arginine-rich apoprotein in the plasma and various ultracentrifugal fractions obtained from control and cholesterol-fed rats. In rats fed the cholesterol diet, the total plasma arginine-rich apoprotein increased from a control value of approximately 29 mg/dl to 47 mg/dl. The method of ultracentrifugation, however, was found to markedly alter the quantitative results. When the 60 Ti rotor was used at maximum speed to isolate the ultracentrifugal fractions, less than 50% of the total plasma arginine-rich apoprotein was associated with the lipoproteins in the d < 1.006 or the d 1.006-1.02, 1.02-1.063, or 1.063-1.21 ultracentrifugal fractions. By contrast, after limited ultracentrifugation with the 40 rotor, much less arginine-rich apoprotein was lost, with approximately 20% of the arginine-rich apoprotein in control rats and 10% in cholesterol-fed rats found in the d > 1.21 fraction. Significant alterations in the arginine-rich apoprotein quantitation notwithstanding, the observations of increased arginine-rich apoprotein in the B-VLDL, intermediate fraction, and HDL(c) following cholesterol feeding remained valid. However, precise quantitation awaits refinements in lipoprotein isolation techniques."}
{"id": "PMID:194009", "title": "Parturition in goats: studies on the interactions between the foetus, placenta, prostaglandin F and progesterone before parturition, at term or at parturition induced prematurely by corticotrophin infusion of the foetus.", "content": "Relationships between foetal corticosteroid concentrations, utero-ovarian prostaglandin F (PGF) and maternal peripheral progesterone have been examined in detail in goats shortly before spontaneous parturition at term. Foetal corticosteroids increased during the last 13-11 days of gestation and particularly sharply during the last 3 days and even during advanced labour. About 24 h before parturition, acute releases of PGF were evident in the vein draining the pregnant uterine horn, and these corresponded closely to the time of luteal regression. Further release of PGF occured when progesterone declined to low levels, probably reflecting in the course of labour. The changes observed before premature parturition, induced by infusing ACTH into foetal goats, were similar except for the more rapid increase in foetal corticosteoid concentrations. Immature neonates born after ACTH treatment were viable, placental delivery was normal and lactogenesis occurred in the mothers indicating that the treatment promoted full expression of the critical perinatal events. The early, acute releases of PGF were ipsilateral to the ACTH-infused foetus and were luteolytic provided the corpora lutea were also on that side. Luteolysis failed or was abnormally delayed if the corpora lutea were contralateral and prolonged ACTH treatment of the foetuses in such cases caused foetal death probably because of premature failure of the placenta. Similar findings were noted if ACTH infusion of the foetus was accompanied by simultaneous progesterone treatment of the mothers in order block the induction of labour. It was suggested that placental changes occurring during foetal hypercortisolism might be caused by increased placental oestrogen synthesis and the effect of this on the foeto-maternal junction along with a stimulatory action on PG synthesis in the maternal placenta. Experimental disruption of the normal sequence of events, when labour was blocked by progesterone, proved to be lethal to the foetus if the loss of placental integrity progressed sufficiently. The chain of regulatory signals linking increased activity of the foetal adrenal with parturition thus appears to involve stimulation of oestrogen biosynthesis, PGF release from the maternal placenta and the start of physical changes at the placental junction. Provided the foetus and corpora lutea are ipsilateral, the early releases of PGF effect luteolysis and a withdrawal of progesterone from the maternal circulation. When progesterone concentrations are sufficiently low, labour is initiated and its progress reflected by further release of PGF. The control mechanisms, which also provide for the final maturation of the foetus, clearly enable a close synchronization of the various perinatal events which are essential for the transition from foetal to postnatal life.", "contents": "Parturition in goats: studies on the interactions between the foetus, placenta, prostaglandin F and progesterone before parturition, at term or at parturition induced prematurely by corticotrophin infusion of the foetus. Relationships between foetal corticosteroid concentrations, utero-ovarian prostaglandin F (PGF) and maternal peripheral progesterone have been examined in detail in goats shortly before spontaneous parturition at term. Foetal corticosteroids increased during the last 13-11 days of gestation and particularly sharply during the last 3 days and even during advanced labour. About 24 h before parturition, acute releases of PGF were evident in the vein draining the pregnant uterine horn, and these corresponded closely to the time of luteal regression. Further release of PGF occured when progesterone declined to low levels, probably reflecting in the course of labour. The changes observed before premature parturition, induced by infusing ACTH into foetal goats, were similar except for the more rapid increase in foetal corticosteoid concentrations. Immature neonates born after ACTH treatment were viable, placental delivery was normal and lactogenesis occurred in the mothers indicating that the treatment promoted full expression of the critical perinatal events. The early, acute releases of PGF were ipsilateral to the ACTH-infused foetus and were luteolytic provided the corpora lutea were also on that side. Luteolysis failed or was abnormally delayed if the corpora lutea were contralateral and prolonged ACTH treatment of the foetuses in such cases caused foetal death probably because of premature failure of the placenta. Similar findings were noted if ACTH infusion of the foetus was accompanied by simultaneous progesterone treatment of the mothers in order block the induction of labour. It was suggested that placental changes occurring during foetal hypercortisolism might be caused by increased placental oestrogen synthesis and the effect of this on the foeto-maternal junction along with a stimulatory action on PG synthesis in the maternal placenta. Experimental disruption of the normal sequence of events, when labour was blocked by progesterone, proved to be lethal to the foetus if the loss of placental integrity progressed sufficiently. The chain of regulatory signals linking increased activity of the foetal adrenal with parturition thus appears to involve stimulation of oestrogen biosynthesis, PGF release from the maternal placenta and the start of physical changes at the placental junction. Provided the foetus and corpora lutea are ipsilateral, the early releases of PGF effect luteolysis and a withdrawal of progesterone from the maternal circulation. When progesterone concentrations are sufficiently low, labour is initiated and its progress reflected by further release of PGF. The control mechanisms, which also provide for the final maturation of the foetus, clearly enable a close synchronization of the various perinatal events which are essential for the transition from foetal to postnatal life."}
{"id": "PMID:194010", "title": "Urinary steroid excretion by the squirrel monkey (Saimuri sciureus).", "content": "Urinary steroids and steroid conjugates were measured in the squirrel monkey (Saimuri sciureus). The principal steroids excreted were cortisol, 11beta,17alpha,20beta,21-tetrahydroxy-4-pregnen-3-one (20beta-dihydrocortisol), alpha- and beta-cortol and alpha- and beta-cortolone. The majority of the steroids were excreted unconjugated and a conspicuous feature of the pattern was the large amount of urinary free cortisol. Unlike man there was an insignificant excretion of 3alpha,17alpha,21-trihydroxy-5beta-pregnane-11,20-dione (tetrahydrocortisone) and 3alpha,11beta,17alpha,21-tetrahydroxy-5beta-pregnan-20-one (tetrahydrocortisol). A steroid not previously identified in urine from any species was one of the major glucuronide conjugates; it was characterized as having the structure 3beta,17alpha,20xi,21-tetrahydroxy-5beta-pregnan-11-one. Administration of dexamethosone resulted in complete suppression of steroid output, whilst the response to adrenocorticotrophic hormone was inconstant.", "contents": "Urinary steroid excretion by the squirrel monkey (Saimuri sciureus). Urinary steroids and steroid conjugates were measured in the squirrel monkey (Saimuri sciureus). The principal steroids excreted were cortisol, 11beta,17alpha,20beta,21-tetrahydroxy-4-pregnen-3-one (20beta-dihydrocortisol), alpha- and beta-cortol and alpha- and beta-cortolone. The majority of the steroids were excreted unconjugated and a conspicuous feature of the pattern was the large amount of urinary free cortisol. Unlike man there was an insignificant excretion of 3alpha,17alpha,21-trihydroxy-5beta-pregnane-11,20-dione (tetrahydrocortisone) and 3alpha,11beta,17alpha,21-tetrahydroxy-5beta-pregnan-20-one (tetrahydrocortisol). A steroid not previously identified in urine from any species was one of the major glucuronide conjugates; it was characterized as having the structure 3beta,17alpha,20xi,21-tetrahydroxy-5beta-pregnan-11-one. Administration of dexamethosone resulted in complete suppression of steroid output, whilst the response to adrenocorticotrophic hormone was inconstant."}
{"id": "PMID:194011", "title": "Regulation of cholesterol synthesis by low density lipoprotein in isolated human lymphocytes. Comparison of cells from normal subjects and patients with homozygous familial hypercholesterolemia and abetalipoproteinemia.", "content": "The rate of cholesterol synthesis from [14C]acetate was low in circulating blood lymphocytes freshly isolated from 17 normal subjects and 4 subjects with homozygous FH. On the other hand, the rate of cholesterol synthesis was two to fourfold above normal in freshly isolated lymphocytes from two subjects with abetalipoproteinemia. When the lymphocytes from subjects with all three genotypes were incubated for 48-72 h in the absence of lipoproteins, the rate of cholesterol synthesis increased by 5-15-fold. The subsequent addition of plasma LDL, but not HDL, rapidly suppressed cholesterol synthesis in the lymphocytes from normal subjects. In contrast, lymphocytes from the FH homozygotes, which have been shown previously to be deficient in cell surface LDL receptors, were resistant to LDL-mediated suppression of cholesterol synthesis. In addition to its ability to suppress cholesterol synthesis after it had been elevated by incubation of the cells in the absence of lipoproteins, LDL was able to suppress the induction of the enhanced rate of sterol synthesis when added to normal lymphocytes immediately after their isolation from the bloodstream. In contrast to the former action of LDL, the latter action of LDL-i.e., the suppression of induction of sterol synthesis-also occurred to a limited extent in lymphocytes from FH homozygotes. However, the FH lymphocytes, but not the normal cells, could be made resistant to this action of LDL by inclusion in the incubation medium of lipoprotein-deficient serum (30 percent, vol/vol) plus HDL (1 mg protein/ml). Considered together with previous data demonstrating a deficiency of LDL receptors in freshly isolated lymphocytes from FH homozygotes, the current studies provide evidence in support of the hypothesis that the interaction of plasma LDL with its cell surface receptor serves to regulate cholesterol synthesis in human lymphocytes.", "contents": "Regulation of cholesterol synthesis by low density lipoprotein in isolated human lymphocytes. Comparison of cells from normal subjects and patients with homozygous familial hypercholesterolemia and abetalipoproteinemia. The rate of cholesterol synthesis from [14C]acetate was low in circulating blood lymphocytes freshly isolated from 17 normal subjects and 4 subjects with homozygous FH. On the other hand, the rate of cholesterol synthesis was two to fourfold above normal in freshly isolated lymphocytes from two subjects with abetalipoproteinemia. When the lymphocytes from subjects with all three genotypes were incubated for 48-72 h in the absence of lipoproteins, the rate of cholesterol synthesis increased by 5-15-fold. The subsequent addition of plasma LDL, but not HDL, rapidly suppressed cholesterol synthesis in the lymphocytes from normal subjects. In contrast, lymphocytes from the FH homozygotes, which have been shown previously to be deficient in cell surface LDL receptors, were resistant to LDL-mediated suppression of cholesterol synthesis. In addition to its ability to suppress cholesterol synthesis after it had been elevated by incubation of the cells in the absence of lipoproteins, LDL was able to suppress the induction of the enhanced rate of sterol synthesis when added to normal lymphocytes immediately after their isolation from the bloodstream. In contrast to the former action of LDL, the latter action of LDL-i.e., the suppression of induction of sterol synthesis-also occurred to a limited extent in lymphocytes from FH homozygotes. However, the FH lymphocytes, but not the normal cells, could be made resistant to this action of LDL by inclusion in the incubation medium of lipoprotein-deficient serum (30 percent, vol/vol) plus HDL (1 mg protein/ml). Considered together with previous data demonstrating a deficiency of LDL receptors in freshly isolated lymphocytes from FH homozygotes, the current studies provide evidence in support of the hypothesis that the interaction of plasma LDL with its cell surface receptor serves to regulate cholesterol synthesis in human lymphocytes."}
{"id": "PMID:194012", "title": "On the occurrence of cytochrome P-450 and aryl hydrocarbon hydroxylase activity in rat brain.", "content": "The difference spectra of the carbon monoxide-complex of dithionite-reduced rat brain microsomes, compared with both reduced microsomes, alone, and the carbon monoxide-complex of oxidized microsomes, indicate the presence of small amounts of cytochrome P-450 in brain. As in liver, cytochrome P-450 in brain is degraded in vitro to its inactive form, cytochrome P-420 by methylmercury chloride. Aryl hydrocarbon hydroxylase activity is also present in rat brain microsomes and, at lower specific activity, in brain homogenates. This carcinogen metabolizing activity is increased four-fold in rats pretreated with 3-methylcholanthrene.", "contents": "On the occurrence of cytochrome P-450 and aryl hydrocarbon hydroxylase activity in rat brain. The difference spectra of the carbon monoxide-complex of dithionite-reduced rat brain microsomes, compared with both reduced microsomes, alone, and the carbon monoxide-complex of oxidized microsomes, indicate the presence of small amounts of cytochrome P-450 in brain. As in liver, cytochrome P-450 in brain is degraded in vitro to its inactive form, cytochrome P-420 by methylmercury chloride. Aryl hydrocarbon hydroxylase activity is also present in rat brain microsomes and, at lower specific activity, in brain homogenates. This carcinogen metabolizing activity is increased four-fold in rats pretreated with 3-methylcholanthrene."}
{"id": "PMID:194013", "title": "Guanosine 3',5'-cyclic monophosphate and the in vitro physiology of frog photoreceptor membranes.", "content": "Frog rod outer segments freshly detached from dark-adapted retinas contain approximately 1-2 molecules of guanosine 3',5'-cyclic monophosphate (cyclic GMP) for every 100 molecules of visual pigment present. This cyclic GMP decays to 5'-GMP, and the conversion is accelerated upon illumination of the outer segments. Bleaching one rhodopsin molecule can lead to the hydrolysis of 1,000-2,000 molecules of cyclic GMP within 100-300 ms. The decline in cyclic GMP concentration becomes larger as illumination increases, and varies with the logarithm of light intensity at levels which bleach between 5 X 10(2) and 5 X 10(5) rhodopsin molecules per outer segment-second. Light suppression of plasma membrane permeability, assayed in vitro as light suppression of outer segment swelling in a modified Ringer's solution, occurs over this same range of light intensity. The correlation between cyclic GMP and permeability or swelling is maintained in the presence of two pharmacological perturbations: papaverine, a phosphodiesterase inhibitor, increases both cyclic GMP levels and the dark permeability of the plasma membrane; and beta,gamma-methylene ATP increases the effectiveness of light in suppressing both permeability and cyclic GMP levels.", "contents": "Guanosine 3',5'-cyclic monophosphate and the in vitro physiology of frog photoreceptor membranes. Frog rod outer segments freshly detached from dark-adapted retinas contain approximately 1-2 molecules of guanosine 3',5'-cyclic monophosphate (cyclic GMP) for every 100 molecules of visual pigment present. This cyclic GMP decays to 5'-GMP, and the conversion is accelerated upon illumination of the outer segments. Bleaching one rhodopsin molecule can lead to the hydrolysis of 1,000-2,000 molecules of cyclic GMP within 100-300 ms. The decline in cyclic GMP concentration becomes larger as illumination increases, and varies with the logarithm of light intensity at levels which bleach between 5 X 10(2) and 5 X 10(5) rhodopsin molecules per outer segment-second. Light suppression of plasma membrane permeability, assayed in vitro as light suppression of outer segment swelling in a modified Ringer's solution, occurs over this same range of light intensity. The correlation between cyclic GMP and permeability or swelling is maintained in the presence of two pharmacological perturbations: papaverine, a phosphodiesterase inhibitor, increases both cyclic GMP levels and the dark permeability of the plasma membrane; and beta,gamma-methylene ATP increases the effectiveness of light in suppressing both permeability and cyclic GMP levels."}
{"id": "PMID:194014", "title": "Single case study. A head movement disorder occurring in dreaming sleep.", "content": "A movement disorder specifically associated with dreaming sleep was observed in an otherwise healthy young woman. It was characterized by gross head movements, nightly occurrence, and no awakening. The patient had a lifelong history of the disorder, as did her brother.", "contents": "Single case study. A head movement disorder occurring in dreaming sleep. A movement disorder specifically associated with dreaming sleep was observed in an otherwise healthy young woman. It was characterized by gross head movements, nightly occurrence, and no awakening. The patient had a lifelong history of the disorder, as did her brother."}
{"id": "PMID:194020", "title": "Fatal cases of lipid storage myopathy with carnitine deficiency.", "content": "Three patients affected by a progressive myopathy with rapid lethal evolution are presented. Excessive lipid storage was found in type 1 fibres of muscle and in liver, kidney, and myocardium. Carnitine concentrations were markedly reduced in muscle, plasma, and heart, significantly lower in the liver, and normal in kidney. D-L carnitine replacement therapy was ineffective in the only case treated. The relationship of the present cases with the syndrome of lipid storage myopathy and carnitine deficiency is discussed.", "contents": "Fatal cases of lipid storage myopathy with carnitine deficiency. Three patients affected by a progressive myopathy with rapid lethal evolution are presented. Excessive lipid storage was found in type 1 fibres of muscle and in liver, kidney, and myocardium. Carnitine concentrations were markedly reduced in muscle, plasma, and heart, significantly lower in the liver, and normal in kidney. D-L carnitine replacement therapy was ineffective in the only case treated. The relationship of the present cases with the syndrome of lipid storage myopathy and carnitine deficiency is discussed."}
{"id": "PMID:194021", "title": "Antagonism of the paralysis produced by botulinum toxin in the rat. The effects of tetraethylammonium, guanidine and 4-aminopyridine.", "content": "The injection of botulinum toxin type A into the hind-leg of adult rats causes complete paralysis of the leg lasting for several weeks. In the extensor digitorum longus (EDL) muscle transmitter release is reduced to a level of less than 1% of normal. Tetraethylammonium (TEA) and guanidine in concentrations of about 3 mM restore, in EDL muslces in vitro, neuromuscular transmission to about the normal level, provided that the external calcium concentration is 4 mM or higher. 4-Aminopyridine (4-AP) has similar restorative effect but is about 20-30 times more potent. Unlike TEA and guanidine, 4-AP is effective when the ambient calcium concentration is 2 mM; this drug is therefore also active in vivo. The intravenous injection of 4-AP (5 mg/kg body weight) restores neuromuscular transmission from complete paralysis by botulinum toxin to a normal level as shown by the recording of almost normal twitch and tetanic tensions in the EDL muscle. In rats paralysed by a lethal dose of botulinum toxin, the intraperitoneal administration of 4-AP restores general motor activity, the effect lasting 1-2 hours. A study of the effects of these drugs on spontaneous and evoked transmitter release suggests that all three compounds increase the level of free calcium inside the nerve terminals. In botulinum poisoning the transmitter release mechanism appears to be intact, but a reduced sensitivity to calcium has been shown (Cull-Candy et al. 1976), and this could explain why the drugs restore evoked transmitter release in botulinum poisoning.", "contents": "Antagonism of the paralysis produced by botulinum toxin in the rat. The effects of tetraethylammonium, guanidine and 4-aminopyridine. The injection of botulinum toxin type A into the hind-leg of adult rats causes complete paralysis of the leg lasting for several weeks. In the extensor digitorum longus (EDL) muscle transmitter release is reduced to a level of less than 1% of normal. Tetraethylammonium (TEA) and guanidine in concentrations of about 3 mM restore, in EDL muslces in vitro, neuromuscular transmission to about the normal level, provided that the external calcium concentration is 4 mM or higher. 4-Aminopyridine (4-AP) has similar restorative effect but is about 20-30 times more potent. Unlike TEA and guanidine, 4-AP is effective when the ambient calcium concentration is 2 mM; this drug is therefore also active in vivo. The intravenous injection of 4-AP (5 mg/kg body weight) restores neuromuscular transmission from complete paralysis by botulinum toxin to a normal level as shown by the recording of almost normal twitch and tetanic tensions in the EDL muscle. In rats paralysed by a lethal dose of botulinum toxin, the intraperitoneal administration of 4-AP restores general motor activity, the effect lasting 1-2 hours. A study of the effects of these drugs on spontaneous and evoked transmitter release suggests that all three compounds increase the level of free calcium inside the nerve terminals. In botulinum poisoning the transmitter release mechanism appears to be intact, but a reduced sensitivity to calcium has been shown (Cull-Candy et al. 1976), and this could explain why the drugs restore evoked transmitter release in botulinum poisoning."}
{"id": "PMID:194022", "title": "Immunobiology of primary intracranial tumors.", "content": "The avian sarcoma virus-induced glioma model in rats was used to study the effectiveness of immunotherapy, namely, Bacillus Calmette-Gu\u00e9rin (BCG) with or without sarcoma cells and/or chemotherapy with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), upon survival times. The most consistent prolongation of survival time was produced by triple therapy: BCG + intraperitoneally administered sarcoma cells + intravenously administered BCNU.", "contents": "Immunobiology of primary intracranial tumors. The avian sarcoma virus-induced glioma model in rats was used to study the effectiveness of immunotherapy, namely, Bacillus Calmette-Gu\u00e9rin (BCG) with or without sarcoma cells and/or chemotherapy with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), upon survival times. The most consistent prolongation of survival time was produced by triple therapy: BCG + intraperitoneally administered sarcoma cells + intravenously administered BCNU."}
{"id": "PMID:194023", "title": "Relative toxicity and metabolic effects of cholecalciferol and 25-hydroxycholecalciferol in chicks.", "content": "The relative toxicity and metabolic effectiveness of cholecalciferol (CC) and 25-hydroxycholecalciferol (25-HCC) in chicks were evaluated by feeding six graded levels of each and observing gross and microscopic pathology as well as several metabolic parameters of calcium metabolism. Renal tubular calcification was observed when CC was fed at the rate of 10.0 mg/kg of diet and when 25-HCC was fed at the rate of 0.1 mg/kg diet. Thus, 100-fold increase in toxicity results when the hydroxylated form of CC is fed. Both microscopic renal lesions and increased renal calcium and inorganic phosphate concentrations occurred in chicks with normal serum calcium concentrations.", "contents": "Relative toxicity and metabolic effects of cholecalciferol and 25-hydroxycholecalciferol in chicks. The relative toxicity and metabolic effectiveness of cholecalciferol (CC) and 25-hydroxycholecalciferol (25-HCC) in chicks were evaluated by feeding six graded levels of each and observing gross and microscopic pathology as well as several metabolic parameters of calcium metabolism. Renal tubular calcification was observed when CC was fed at the rate of 10.0 mg/kg of diet and when 25-HCC was fed at the rate of 0.1 mg/kg diet. Thus, 100-fold increase in toxicity results when the hydroxylated form of CC is fed. Both microscopic renal lesions and increased renal calcium and inorganic phosphate concentrations occurred in chicks with normal serum calcium concentrations."}
{"id": "PMID:194026", "title": "Beta adrenergic receptor labeling in intact animals with 125I-hydroxybenzylpindolol.", "content": "After the intravenous administration to mice of 125I-hydroxybenzylpindolol (125I-HYP), a potent beta adrenergic antagonist, particulate bound radioactivity in brain, heart and lung is selectively associated with beta adrenergic receptor binding sites. The amount of total and bound radioactivity in these tissues is time dependent, reaching peak values at about 5 minutes after injection, and increases approximately linearly with increasing 125I-HYP doses. The lung has the highest levels of radioactivity as well as the highest proportion of bound to total radioactivity. The amount of specifically bound 125I-HYP is markedly reduced by simultaneously injecting a beta adrenergic bound 125I-HYP is markedly reduced by simultaneously injecting a beta adrenergic agonist or antagonist, although the total amount of radioactivity in the tissues is not affected. The beta antagonist (-)-propranolol reduces specific 125I-HYP binding 50% at doses of 0.01, 0.03 and 0.004 mg/kg in brain, heart and lung, respectively. Specific 125I-HYP binding is stereospecific in these tissues as (+)-propranolol is only 1 to 2% as effective as (-)-propranolol in reducing binding. The beta agonist (-)-isoproterenol has ID50 values in the range of 2 to 20 mg/kg, whereas the alpha adrenergic antagonist, phentolamine does not reduce 125I-HYP binding. Although some radioactivity is associated with particulate fractions from the liver, little, if any, specific binding of 125I-HYP to a beta adrenergic receptor is demonstrable. The characteristics of 125I-HYP binding in mouse heart, lung and brain are those expected for the recognition site of the beta adrenergic receptor and thus provide a method for labeling the beta adrenergic receptor in vivo.", "contents": "Beta adrenergic receptor labeling in intact animals with 125I-hydroxybenzylpindolol. After the intravenous administration to mice of 125I-hydroxybenzylpindolol (125I-HYP), a potent beta adrenergic antagonist, particulate bound radioactivity in brain, heart and lung is selectively associated with beta adrenergic receptor binding sites. The amount of total and bound radioactivity in these tissues is time dependent, reaching peak values at about 5 minutes after injection, and increases approximately linearly with increasing 125I-HYP doses. The lung has the highest levels of radioactivity as well as the highest proportion of bound to total radioactivity. The amount of specifically bound 125I-HYP is markedly reduced by simultaneously injecting a beta adrenergic bound 125I-HYP is markedly reduced by simultaneously injecting a beta adrenergic agonist or antagonist, although the total amount of radioactivity in the tissues is not affected. The beta antagonist (-)-propranolol reduces specific 125I-HYP binding 50% at doses of 0.01, 0.03 and 0.004 mg/kg in brain, heart and lung, respectively. Specific 125I-HYP binding is stereospecific in these tissues as (+)-propranolol is only 1 to 2% as effective as (-)-propranolol in reducing binding. The beta agonist (-)-isoproterenol has ID50 values in the range of 2 to 20 mg/kg, whereas the alpha adrenergic antagonist, phentolamine does not reduce 125I-HYP binding. Although some radioactivity is associated with particulate fractions from the liver, little, if any, specific binding of 125I-HYP to a beta adrenergic receptor is demonstrable. The characteristics of 125I-HYP binding in mouse heart, lung and brain are those expected for the recognition site of the beta adrenergic receptor and thus provide a method for labeling the beta adrenergic receptor in vivo."}
{"id": "PMID:194029", "title": "Side effects of immersion-type cleansers on the metal components of dentures.", "content": "Three metals were immersed in eight denture cleansing solutions for a period of 240 hours to determine the relative side effects of these cleansers upon various metal components of complete and removable partial dentures. Conclusions drawn from this study are: 1. Commercial bleaches and unbuffered hypochlorite solutions should not be used on dentures with metal components. 2. Routine use of buffered hypochlorite solutions may cause surface damage to aluminum-base material. 3. Stainless steel (orthodontic wire) will tarnish after continued exposure to buffered and unbuffered hypochlorite solutions. 4. Further research is necessary to delineate the effects of existing denture cleansers and to improve on their effectiveness and safety.", "contents": "Side effects of immersion-type cleansers on the metal components of dentures. Three metals were immersed in eight denture cleansing solutions for a period of 240 hours to determine the relative side effects of these cleansers upon various metal components of complete and removable partial dentures. Conclusions drawn from this study are: 1. Commercial bleaches and unbuffered hypochlorite solutions should not be used on dentures with metal components. 2. Routine use of buffered hypochlorite solutions may cause surface damage to aluminum-base material. 3. Stainless steel (orthodontic wire) will tarnish after continued exposure to buffered and unbuffered hypochlorite solutions. 4. Further research is necessary to delineate the effects of existing denture cleansers and to improve on their effectiveness and safety."}
{"id": "PMID:194028", "title": "Microiontophoretic studies of the effects of cylic nucleotides on excitability of neurones in the rat cerebral cortex.", "content": "1. Responses of cerebral cortical neurones to the microiontophoretic application of acetylcholine, noradrenaline, cyclic adenosine 3',5'-monophosphate (cyclic AMP) and cyclic guanosine 3',5'-monophosphate (cyclic GMP) were examined.2. The application of acetylcholine and cyclic GMP to identified pyramidal tract neurones resulted in an increased frequency of firing in a large number of cells. Upon application of both substances to cells which could not be identified as pyramidal tract cells, a reduction in the frequency of spontaneous firing was sometimes observed.3. Careful current controls had no effect on the cells discussed here, indicating that the observed responses were not due to the iontophoretic currents. Also, the electro-osmotic ejection of cyclic GMP (outward current) produced similar changes of cell firing to those which followed iontophoretic application (inward current).4. The microiontophoretic application of atropine resulted in a blockade of acetylcholine responses while leaving responses to cyclic GMP unaffected. This suggests that cyclic GMP was not acting indirectly by releasing acetylcholine from presynaptic endings.5. Ejection of cyclic GMP from solutions containing calcium ions produced responses comparable to those produced by cyclic GMP alone. It is unlikely therefore that cyclic GMP was causing excitation by chelating calcium.6. Applications of noradrenaline and cyclic AMP produced a reduction in the spontaneous discharge rate of most neurones tested.7. Phosphodiesterase inhibitors such as ICI 63,197 caused a potentiation of the noradrenaline responses of pyramidal tract neurones.8. 5'-adenosine monophosphate produced a powerful depression of all cells to which it was applied. This action was blocked by aminophylline, suggesting the effect was mediated through an adenosine receptor. Responses to cyclic AMP were usually not abolished, but were reduced by about 50% in amplitude.9. These results are consistent with the hypothesis that cyclic AMP may mediate some neuronal effects of noradrenaline and cyclic GMP may mediate some effects of acetylcholine. The results are also consistent with the suggestion that the two nucleotides may sometimes mediate opposite cellular responses to humoral stimuli.", "contents": "Microiontophoretic studies of the effects of cylic nucleotides on excitability of neurones in the rat cerebral cortex. 1. Responses of cerebral cortical neurones to the microiontophoretic application of acetylcholine, noradrenaline, cyclic adenosine 3',5'-monophosphate (cyclic AMP) and cyclic guanosine 3',5'-monophosphate (cyclic GMP) were examined.2. The application of acetylcholine and cyclic GMP to identified pyramidal tract neurones resulted in an increased frequency of firing in a large number of cells. Upon application of both substances to cells which could not be identified as pyramidal tract cells, a reduction in the frequency of spontaneous firing was sometimes observed.3. Careful current controls had no effect on the cells discussed here, indicating that the observed responses were not due to the iontophoretic currents. Also, the electro-osmotic ejection of cyclic GMP (outward current) produced similar changes of cell firing to those which followed iontophoretic application (inward current).4. The microiontophoretic application of atropine resulted in a blockade of acetylcholine responses while leaving responses to cyclic GMP unaffected. This suggests that cyclic GMP was not acting indirectly by releasing acetylcholine from presynaptic endings.5. Ejection of cyclic GMP from solutions containing calcium ions produced responses comparable to those produced by cyclic GMP alone. It is unlikely therefore that cyclic GMP was causing excitation by chelating calcium.6. Applications of noradrenaline and cyclic AMP produced a reduction in the spontaneous discharge rate of most neurones tested.7. Phosphodiesterase inhibitors such as ICI 63,197 caused a potentiation of the noradrenaline responses of pyramidal tract neurones.8. 5'-adenosine monophosphate produced a powerful depression of all cells to which it was applied. This action was blocked by aminophylline, suggesting the effect was mediated through an adenosine receptor. Responses to cyclic AMP were usually not abolished, but were reduced by about 50% in amplitude.9. These results are consistent with the hypothesis that cyclic AMP may mediate some neuronal effects of noradrenaline and cyclic GMP may mediate some effects of acetylcholine. The results are also consistent with the suggestion that the two nucleotides may sometimes mediate opposite cellular responses to humoral stimuli."}
{"id": "PMID:194036", "title": "Anaerobiosis and symbiosis with bacteria in free-living ciliates.", "content": "Marine, sediment-dwelling ciliates were examined for cytochrome oxidase activity by a cytochemical method and for fine structural details. Species of Plagiopylidae (Trichostomatida), i.e. Plagiopyla frontata, Sonderia vorax and Sonderia sp., and of Heterotrichda, i.e., Parablepharisma pellitum, Parablepharisma sp., Metopus contortus, Metopus vestitus and Caenomorpha capucina; previously considered to be obligate anaerobes because of their sulfide-containing habitat, do not have cytochrome oxidase activity or mitochondria with cristae or tubuli. The evolutionary origin and significance of anaerobic ciliates is discussed. Most of the anaerobic ciliates harbor a flora of ecto- and endosymbiotic bacteria as demonstrated by transmission and scanning electron micrographs. It is speculated that the bacteria may utilize the metabolic end products of the protozoa for growth and energy yielding processes. These associations are also compared with other, previously described cases of symbiosis involving prokaryotes and protozoa.", "contents": "Anaerobiosis and symbiosis with bacteria in free-living ciliates. Marine, sediment-dwelling ciliates were examined for cytochrome oxidase activity by a cytochemical method and for fine structural details. Species of Plagiopylidae (Trichostomatida), i.e. Plagiopyla frontata, Sonderia vorax and Sonderia sp., and of Heterotrichda, i.e., Parablepharisma pellitum, Parablepharisma sp., Metopus contortus, Metopus vestitus and Caenomorpha capucina; previously considered to be obligate anaerobes because of their sulfide-containing habitat, do not have cytochrome oxidase activity or mitochondria with cristae or tubuli. The evolutionary origin and significance of anaerobic ciliates is discussed. Most of the anaerobic ciliates harbor a flora of ecto- and endosymbiotic bacteria as demonstrated by transmission and scanning electron micrographs. It is speculated that the bacteria may utilize the metabolic end products of the protozoa for growth and energy yielding processes. These associations are also compared with other, previously described cases of symbiosis involving prokaryotes and protozoa."}
{"id": "PMID:194037", "title": "Some biochemical properties of mitochondria isolated from Euglena gracilis.", "content": "Mitochondria were isolated from Euglena gracilis strain Z by pressure-breakage of the cells and sucrose-cushion centrifugation. Multiple peaks (2-4) were observed in the rate of phosphorylation with Mg-ADP-phosphate concentration curves. The phosphorylative and oxidative activities were highest with NADH as the substrate, moderate with succinate, and lowest with glutamate. Inhibition of phosphorylation with 2,4-dinitrophenol and carbonyl cyanide, m-chlorophenylhydrazone gave sigmoidal concentration curves, with the extent of inhibition by DNP depending on the substrate used. Inhibition of phosphorylation by valinomycin, atractyloside, or carboxyatractyloside was only approximately 60%. Oligomycin inhibited phosphorylation in 2 phases at low and high concentrations; it inhibited Mg-ATPase in a sigmoidal fashion. Both phosphorylation and oxidation had discontinuities in Arrhenius plots at 34 C and 18 C. The relative Mg2+-dependent nucleoside triphosphatase activity was: 1 for ATP and GTP, 0.6 for ITP, 0.15 for CTP and UTP; with Ca2+ in place pf Mg2+ this activity was 0.35. Both DNP and CCCP stimulated the Mg-ATPase 50-200%. The optimal pH for the stimulation was approximately 7 regardless of the uncoupler used, and approximately 8 without the uncouplers. The few differences observed between mitochodria from Euglena and those from other sources are probably due to the fragmentation of the reticular mitochondrial structure during isolation and not to unique characteristics of these mitochondria.", "contents": "Some biochemical properties of mitochondria isolated from Euglena gracilis. Mitochondria were isolated from Euglena gracilis strain Z by pressure-breakage of the cells and sucrose-cushion centrifugation. Multiple peaks (2-4) were observed in the rate of phosphorylation with Mg-ADP-phosphate concentration curves. The phosphorylative and oxidative activities were highest with NADH as the substrate, moderate with succinate, and lowest with glutamate. Inhibition of phosphorylation with 2,4-dinitrophenol and carbonyl cyanide, m-chlorophenylhydrazone gave sigmoidal concentration curves, with the extent of inhibition by DNP depending on the substrate used. Inhibition of phosphorylation by valinomycin, atractyloside, or carboxyatractyloside was only approximately 60%. Oligomycin inhibited phosphorylation in 2 phases at low and high concentrations; it inhibited Mg-ATPase in a sigmoidal fashion. Both phosphorylation and oxidation had discontinuities in Arrhenius plots at 34 C and 18 C. The relative Mg2+-dependent nucleoside triphosphatase activity was: 1 for ATP and GTP, 0.6 for ITP, 0.15 for CTP and UTP; with Ca2+ in place pf Mg2+ this activity was 0.35. Both DNP and CCCP stimulated the Mg-ATPase 50-200%. The optimal pH for the stimulation was approximately 7 regardless of the uncoupler used, and approximately 8 without the uncouplers. The few differences observed between mitochodria from Euglena and those from other sources are probably due to the fragmentation of the reticular mitochondrial structure during isolation and not to unique characteristics of these mitochondria."}
{"id": "PMID:194038", "title": "Cyclic AMP and the preparation of the mouse uterus for implantation.", "content": "Experiments are described that demonstrate the ability of dibutyryl cyclic AMP (dcAMP) to induced oestrogen-like changes in the uteri of ovariectomized mice treated with progesterone. A single intraluminal injection of 6-14 micrograms dcAMP in 0-02 ml phosphate-buffered saline promoted cell division in the uterine stroma and sensitized the endometrium so that a decidual reaction could be induced by a subsequent injection of arachis oil into the uterine lumen. Since dcAMP has already been shown to induce implantation of diapausing mouse blastocysts in the absence of oestrogen, it is suggested that cyclic AMP is involved in egg implantation in rodents.", "contents": "Cyclic AMP and the preparation of the mouse uterus for implantation. Experiments are described that demonstrate the ability of dibutyryl cyclic AMP (dcAMP) to induced oestrogen-like changes in the uteri of ovariectomized mice treated with progesterone. A single intraluminal injection of 6-14 micrograms dcAMP in 0-02 ml phosphate-buffered saline promoted cell division in the uterine stroma and sensitized the endometrium so that a decidual reaction could be induced by a subsequent injection of arachis oil into the uterine lumen. Since dcAMP has already been shown to induce implantation of diapausing mouse blastocysts in the absence of oestrogen, it is suggested that cyclic AMP is involved in egg implantation in rodents."}
{"id": "PMID:194039", "title": "Spontaneous malignant histiocytoma with metastasis in a rhesus monkey [Macaca mulatta].", "content": "A malignant histiocytoma was observed on the left arm of a recently imported rhesus monkey. Rapid invasion of deep tissues and tumor growth on the face prompted euthanasia. Necropsy revealed additional neoplastic foci in the lungs, diaphragm, intercostal muscles, pericardium and liver. Microscopically the predominant cell type was histiocytic; some cells had a distinct epithelioid appearance and other were spindle-shaped.", "contents": "Spontaneous malignant histiocytoma with metastasis in a rhesus monkey [Macaca mulatta]. A malignant histiocytoma was observed on the left arm of a recently imported rhesus monkey. Rapid invasion of deep tissues and tumor growth on the face prompted euthanasia. Necropsy revealed additional neoplastic foci in the lungs, diaphragm, intercostal muscles, pericardium and liver. Microscopically the predominant cell type was histiocytic; some cells had a distinct epithelioid appearance and other were spindle-shaped."}
{"id": "PMID:194040", "title": "Expression of Thy 1 antigen in normal and neoplastic mammary cells of mice.", "content": "The expression of Thy 1.2 (theta C3H) antigen was measured on the membranes of normal and neoplastic RIII and C3H mammary cells. Competitive inhibition assays revealed that the average membrane content of Thy 1.2 in mammary tissues was about equal to that of lymph node cells. Higher percentages of Thy 1.2-positive cells than mammary tumor virus (MuMTV)-positive cells were observed by immunofluorescence, which suggested that not all the Thy 1.2-positive cells recovered from tumors were also MuMTV-positive. Established tissue culture cell lines C3H and RIII MT expressed lower levels of Thy 1.2 than did cells from mammary tumors. Treatment with the synthetic gluco-corticoid dexamethasone increased the average Thy 1.2 expression in cultured mammary tumor cells as well as the levels of RNA-directed DNA polymerase. Since the percentages of Thy 1.2-positive cells also were greater in steroid-treated cultures, while fewer cells were needed to absorb a standard amount of anti-Thy 1.2 activity, it was concluded that dexamethasone enhanced membrane Thy 1.2 expression as well as MuMTV production by the cultured cells.", "contents": "Expression of Thy 1 antigen in normal and neoplastic mammary cells of mice. The expression of Thy 1.2 (theta C3H) antigen was measured on the membranes of normal and neoplastic RIII and C3H mammary cells. Competitive inhibition assays revealed that the average membrane content of Thy 1.2 in mammary tissues was about equal to that of lymph node cells. Higher percentages of Thy 1.2-positive cells than mammary tumor virus (MuMTV)-positive cells were observed by immunofluorescence, which suggested that not all the Thy 1.2-positive cells recovered from tumors were also MuMTV-positive. Established tissue culture cell lines C3H and RIII MT expressed lower levels of Thy 1.2 than did cells from mammary tumors. Treatment with the synthetic gluco-corticoid dexamethasone increased the average Thy 1.2 expression in cultured mammary tumor cells as well as the levels of RNA-directed DNA polymerase. Since the percentages of Thy 1.2-positive cells also were greater in steroid-treated cultures, while fewer cells were needed to absorb a standard amount of anti-Thy 1.2 activity, it was concluded that dexamethasone enhanced membrane Thy 1.2 expression as well as MuMTV production by the cultured cells."}
{"id": "PMID:194041", "title": "Vitamin A contents of rat intestinal epithelium and jejunal mucinous adenocarcinoma.", "content": "Concentrations of retinol and tetinyl esters were assayed in rat intestinal mucosa and in chemically induced transplanted mucinous adenocarcinoma of the jejunum. Lipid extract from the tissues was chromatographed on deactivated alumina to isolate retinol and retinyl esters, which were determined by specific spectrofluorometry. Normal intestinal mucosa tissue contains 556 ng of retinol equivalents as retinyl esters and 303 ng of free retinol/g of wet tissue. The concentration of retinyl esters in the intestinal mucosa from rats carrying the transplanted tumor was 341 ng/g wet tissue; no free retinol was detected in the small intestinal epithelium of these rats. Liver tissue from the tumor-bearing rats contained 157 microng of retinol equivalents as retinyl esters and 136 microng of free retinol/g of wet tissue. The concentration of vitamin A per cell in the adenocarcinoma tissue was about 20 times less than that in intestinal epithelium.", "contents": "Vitamin A contents of rat intestinal epithelium and jejunal mucinous adenocarcinoma. Concentrations of retinol and tetinyl esters were assayed in rat intestinal mucosa and in chemically induced transplanted mucinous adenocarcinoma of the jejunum. Lipid extract from the tissues was chromatographed on deactivated alumina to isolate retinol and retinyl esters, which were determined by specific spectrofluorometry. Normal intestinal mucosa tissue contains 556 ng of retinol equivalents as retinyl esters and 303 ng of free retinol/g of wet tissue. The concentration of retinyl esters in the intestinal mucosa from rats carrying the transplanted tumor was 341 ng/g wet tissue; no free retinol was detected in the small intestinal epithelium of these rats. Liver tissue from the tumor-bearing rats contained 157 microng of retinol equivalents as retinyl esters and 136 microng of free retinol/g of wet tissue. The concentration of vitamin A per cell in the adenocarcinoma tissue was about 20 times less than that in intestinal epithelium."}
{"id": "PMID:194043", "title": "Growth of murine sarcoma virus-transformed rat kidney cells in nude mice: absence of induction of host endogenous viruses.", "content": "Clonal isolates of the normal rat kidney cell line (NRK) transformed by a defective murine sarcoma virus (Kirsten strain) were injected into nude mice of BALB/c background to determine whether the growth of these cells as tumors was accompanied by the induction of host endogenous type C viruses. All the virus-transformed clones produced rapidly growing tumors in nude mice, but neither the induction of mouse endogenous viruses nor the rescue and spread of the transforming sarcoma virus were observed during the growth of tumors. The degree of expression of the tumor virus structural proteins in the transformed cells did not determine the cellular phenotype with regard to tumorigenicity in nude mice, nor did it modify the cellular growth properties in vitro. Consistent with earlier observations with simian virus 40-transformed mouse and rat cells, the ability of sarcoma virus-transformed NRK cells to initiate tumor growth in nude mice appeared to be correlated with anchorage-independent growth in vitro.", "contents": "Growth of murine sarcoma virus-transformed rat kidney cells in nude mice: absence of induction of host endogenous viruses. Clonal isolates of the normal rat kidney cell line (NRK) transformed by a defective murine sarcoma virus (Kirsten strain) were injected into nude mice of BALB/c background to determine whether the growth of these cells as tumors was accompanied by the induction of host endogenous type C viruses. All the virus-transformed clones produced rapidly growing tumors in nude mice, but neither the induction of mouse endogenous viruses nor the rescue and spread of the transforming sarcoma virus were observed during the growth of tumors. The degree of expression of the tumor virus structural proteins in the transformed cells did not determine the cellular phenotype with regard to tumorigenicity in nude mice, nor did it modify the cellular growth properties in vitro. Consistent with earlier observations with simian virus 40-transformed mouse and rat cells, the ability of sarcoma virus-transformed NRK cells to initiate tumor growth in nude mice appeared to be correlated with anchorage-independent growth in vitro."}
{"id": "PMID:194044", "title": "Growth curve of an experimental solid tumor following radiotherapy.", "content": "Because it has long been recognized that the growth of most untreated tumors is well described by Gompertzian or exponential growth curves but that the growth of treated tumors has never been well characterized mathematically, we developed and applied an equation that, while not dependent on restrictive assumptions or unmeasurable variables, was nevertheless capable of describing perturbed as well as unperturbed growth. For the 3964A rat hepatoma, a functional relationship between dose level of radiotherapy and growth-curve response was derived and used for predictive purposes. An implied relationship between tumor size and sensitivity to therapy and some clinical implications were examined.", "contents": "Growth curve of an experimental solid tumor following radiotherapy. Because it has long been recognized that the growth of most untreated tumors is well described by Gompertzian or exponential growth curves but that the growth of treated tumors has never been well characterized mathematically, we developed and applied an equation that, while not dependent on restrictive assumptions or unmeasurable variables, was nevertheless capable of describing perturbed as well as unperturbed growth. For the 3964A rat hepatoma, a functional relationship between dose level of radiotherapy and growth-curve response was derived and used for predictive purposes. An implied relationship between tumor size and sensitivity to therapy and some clinical implications were examined."}
{"id": "PMID:194045", "title": "Quantitative in vivo studies of soluble simian virus 40 tumor-specific transplantation antigens of the mouse.", "content": "Quantitative studies have been performed on the immunogenicity of a membrane-bound antigen of a simian virus 40 (SV40) -induced sarcoma in syngeneic BALB/c mice and of subcellular fractions derived from this tumor. The objectives of the investigation were: a) to develop a quantitative in vivo assay of the tumor-specific transplantation antigen (TSTA) and b) to compare the distribution of histocompatibility antigens, H-2, with that of the SV40 TSTA during several fractionation steps. The immunogenicity of the TSTA-containing fractions was assessed from dose-response curves relating tumor size and the amount of protein used for immunization. After digestion of the tumor cell membranes with a limited amount of papain, H-2 as well as TSTA were present in a soluble form. A single immunization with only 2 microng of the solubilized TSTA reduced the tumor size by 70% compared to that in nonimmunized control animals. The results of several fractionation steps suggest that H-2 and the TSTA are not tightly associated in the solubilized immunogenic material.", "contents": "Quantitative in vivo studies of soluble simian virus 40 tumor-specific transplantation antigens of the mouse. Quantitative studies have been performed on the immunogenicity of a membrane-bound antigen of a simian virus 40 (SV40) -induced sarcoma in syngeneic BALB/c mice and of subcellular fractions derived from this tumor. The objectives of the investigation were: a) to develop a quantitative in vivo assay of the tumor-specific transplantation antigen (TSTA) and b) to compare the distribution of histocompatibility antigens, H-2, with that of the SV40 TSTA during several fractionation steps. The immunogenicity of the TSTA-containing fractions was assessed from dose-response curves relating tumor size and the amount of protein used for immunization. After digestion of the tumor cell membranes with a limited amount of papain, H-2 as well as TSTA were present in a soluble form. A single immunization with only 2 microng of the solubilized TSTA reduced the tumor size by 70% compared to that in nonimmunized control animals. The results of several fractionation steps suggest that H-2 and the TSTA are not tightly associated in the solubilized immunogenic material."}
{"id": "PMID:194047", "title": "Bioactivity of C3H and RIII mammary tumor viruses in virgin female BALB/c mice.", "content": "The bioactivities of C3H and RIII mammary tumor virus (MuMTV) in virgin female BALB/c mice differed. The average number of mammary hyperplastic alveolar nodules per mouse after noduligenic tests was 20.1 in BALB/cfC3H and 10.7 in BALB/cfRIII females. Spontaneous mammary tumor incidence after 20 months of observation was 47.5% in BALB/cfC3H and 14.6% in BALB/cfRIII females (P less than 0.01).  The frequency of lung metastases in mammary tumor-bearing mice was 63.1% in BALB/cfC3H and 16.6% in BALB/cfRIII females (P less than 0.05), although the clinical duration of mammary tumors was the same. These data demonstrated a lower bioactivity of RIII MuMTV when compared to C3H MuMTV in BALB/c mice and suggested that the causative virus may control all the steps of mouse mammary tumor development, including metastasis.", "contents": "Bioactivity of C3H and RIII mammary tumor viruses in virgin female BALB/c mice. The bioactivities of C3H and RIII mammary tumor virus (MuMTV) in virgin female BALB/c mice differed. The average number of mammary hyperplastic alveolar nodules per mouse after noduligenic tests was 20.1 in BALB/cfC3H and 10.7 in BALB/cfRIII females. Spontaneous mammary tumor incidence after 20 months of observation was 47.5% in BALB/cfC3H and 14.6% in BALB/cfRIII females (P less than 0.01).  The frequency of lung metastases in mammary tumor-bearing mice was 63.1% in BALB/cfC3H and 16.6% in BALB/cfRIII females (P less than 0.05), although the clinical duration of mammary tumors was the same. These data demonstrated a lower bioactivity of RIII MuMTV when compared to C3H MuMTV in BALB/c mice and suggested that the causative virus may control all the steps of mouse mammary tumor development, including metastasis."}
{"id": "PMID:194048", "title": "Suppression of infectious murine leukemia virus in wild mice (Mus musculus) by passive immunization.", "content": "Passive immunization with heterologous antivirus antiserum beginning at birth successfully suppressed infectious murine leukemia virus expression in Lake Casitas wild mice (Musmusculus) at 5-7 weeks of age.", "contents": "Suppression of infectious murine leukemia virus in wild mice (Mus musculus) by passive immunization. Passive immunization with heterologous antivirus antiserum beginning at birth successfully suppressed infectious murine leukemia virus expression in Lake Casitas wild mice (Musmusculus) at 5-7 weeks of age."}
{"id": "PMID:194050", "title": "Antibody production and complement system in protein energy malnutrition.", "content": "Antibody production in kwashiorkor and marasmic infants was studied by dividing them into three groups and giving the first group a single dose of trivalent live attenuated polio virus, the second group live attenuated measles virus and the third group diphtheriatoxoid. The production of antibodies was found to be deficient in PEM as compared to normals and diminished more in kwashiorkor than in marasmus cases. The individuals of the complement system were significantly lower in kwashiorkor than in normal controls. However, C3 was the only fraction which is significantly diminished in marasmic infants. The results are discussed and as a conclusion it is suggested that deficient production of antibodies and diminution in the complement system in PEM may explain the susceptibility of such infants to repeated attacks of infection.", "contents": "Antibody production and complement system in protein energy malnutrition. Antibody production in kwashiorkor and marasmic infants was studied by dividing them into three groups and giving the first group a single dose of trivalent live attenuated polio virus, the second group live attenuated measles virus and the third group diphtheriatoxoid. The production of antibodies was found to be deficient in PEM as compared to normals and diminished more in kwashiorkor than in marasmus cases. The individuals of the complement system were significantly lower in kwashiorkor than in normal controls. However, C3 was the only fraction which is significantly diminished in marasmic infants. The results are discussed and as a conclusion it is suggested that deficient production of antibodies and diminution in the complement system in PEM may explain the susceptibility of such infants to repeated attacks of infection."}
{"id": "PMID:194053", "title": "Properties of permissive monkey cells transformed by UV-irradiated simian virus 40.", "content": "African green monkey cells (CV1 line) were infected with UV-irradiated simian virus 40 (SV40), and permissive lines of stably transformed cells were established. These cell lines display the SV40 T-antigen and the growth characteristics typical of nonpermissive transformed cells (e.g., reduced cell density inhibition, reduced serum dependence, ability to overgrow normal cells, and colony formation in soft agar). The level of permissiveness to superinfecting SV40 is fully comparable with that of nontransformed CV1 and BSC-1 lines. The transformed monkey lines also support SV40 plaque production under agar. By Cot analysis, the transformed permissive cells contain, on an average, 1 to 2 SV40 genome equivalents, and the majority of the viral sequences are associated with the high-molecular-weight cellular DNA. No spontaneous production of infectious SV40 has been observed. The transformed permissive monkey cells failed to support the replication of SV40 tsA mutants at the restrictive temperature. To account for this, it is suggested that the gene A product has separate functions for transformation and initiation of viral DNA synthesis, and only the former function is expressed in the transformed permissive monkey cells.", "contents": "Properties of permissive monkey cells transformed by UV-irradiated simian virus 40. African green monkey cells (CV1 line) were infected with UV-irradiated simian virus 40 (SV40), and permissive lines of stably transformed cells were established. These cell lines display the SV40 T-antigen and the growth characteristics typical of nonpermissive transformed cells (e.g., reduced cell density inhibition, reduced serum dependence, ability to overgrow normal cells, and colony formation in soft agar). The level of permissiveness to superinfecting SV40 is fully comparable with that of nontransformed CV1 and BSC-1 lines. The transformed monkey lines also support SV40 plaque production under agar. By Cot analysis, the transformed permissive cells contain, on an average, 1 to 2 SV40 genome equivalents, and the majority of the viral sequences are associated with the high-molecular-weight cellular DNA. No spontaneous production of infectious SV40 has been observed. The transformed permissive monkey cells failed to support the replication of SV40 tsA mutants at the restrictive temperature. To account for this, it is suggested that the gene A product has separate functions for transformation and initiation of viral DNA synthesis, and only the former function is expressed in the transformed permissive monkey cells."}
{"id": "PMID:194054", "title": "Cell cycle dependency of murine cytomegalovirus replication in synchronized 3T3 cells.", "content": "Synchronized murine 3T3 cells have been used to investigate the possible dependency of murine cytomegalovirus replication upon the cell cycle. The normal latent period of 12 h characteristic of asynchronous 3T3 cells was protracted to more than 24 h after an early G1 infection in synchronous cells. In this case viral progeny were not detected until after the initiation of the host S-phase. Cells maintained in the G1 phase did not replicate virus. This failure could not be explained by a decrease in virus penetration but was apparently due to a requirement for an event associated with the host S-phase. Thymidine-induced inhibition of cell cycle traverse also blocked virus replication. Viral DNA synthesis did not initiate until after the initiation of host DNA. In contrast, herpes simplex virus type 1 replicated in 3T3 cells independently of the cell cycle.", "contents": "Cell cycle dependency of murine cytomegalovirus replication in synchronized 3T3 cells. Synchronized murine 3T3 cells have been used to investigate the possible dependency of murine cytomegalovirus replication upon the cell cycle. The normal latent period of 12 h characteristic of asynchronous 3T3 cells was protracted to more than 24 h after an early G1 infection in synchronous cells. In this case viral progeny were not detected until after the initiation of the host S-phase. Cells maintained in the G1 phase did not replicate virus. This failure could not be explained by a decrease in virus penetration but was apparently due to a requirement for an event associated with the host S-phase. Thymidine-induced inhibition of cell cycle traverse also blocked virus replication. Viral DNA synthesis did not initiate until after the initiation of host DNA. In contrast, herpes simplex virus type 1 replicated in 3T3 cells independently of the cell cycle."}
{"id": "PMID:194055", "title": "Expression of tumor-specific transplantation antigen in cell lines transformed by wild-type of tsA mutant simian virus 40.", "content": "The simian virus 40-induced tumor-specific surface antigen(s) (TSSA) and tumor-specific transplantation antigen(s) (TSTA)were detected in cells transformed by wild-type or temperature-sensitive mutant simian virus 40 by an antibody-mediated cytolytic assay for TSSA and an immunization test for TSTA. Cells transformed by tsA mutants, which lose their transformed phenotype when grown at nonpermissive temperatures, nonetheless do express TSSA and TSTA as well as T-antigen at both temperatures.", "contents": "Expression of tumor-specific transplantation antigen in cell lines transformed by wild-type of tsA mutant simian virus 40. The simian virus 40-induced tumor-specific surface antigen(s) (TSSA) and tumor-specific transplantation antigen(s) (TSTA)were detected in cells transformed by wild-type or temperature-sensitive mutant simian virus 40 by an antibody-mediated cytolytic assay for TSSA and an immunization test for TSTA. Cells transformed by tsA mutants, which lose their transformed phenotype when grown at nonpermissive temperatures, nonetheless do express TSSA and TSTA as well as T-antigen at both temperatures."}
{"id": "PMID:194056", "title": "Epstein-barr virus-specific RNA. II. Analysis of polyadenylated viral RNA in restringent, abortive, and prooductive infections.", "content": "The complexity and abundance of Epstein-Barr (EBV)-specific RNA in cell cultures restringently, abortively, and productively infected with EBV has been analyed by hybridization of the infected cell RNA with purified viral DNA. The data indicate the following. (i) Cultures containing productively infected cells contain viral RNA encoded by at least 45% of EBV DNA, and almost all of the species of viral RNA are present in the polyadenylated and polyribosomal RNA fractions. (ii) Restringently infected Namalwa and Raji cultures, which contain only intranuclear antigen, EBNA, and enhanced capacity for growth in vitro, contain EBV RNA encoded by at least 16 and 30% of the EBV DNA, respectively. The polyadenylated and polyribosomal RNA fractions of Raji and Namalwa cells are enriched for a class of EBV RNA encoded by approximately 5% of EBV DNA. The same EBV DNA sequences encode the polyadenylated and polyribosomal RNA of both Raji and Namalwa cells. (iii) After superinfection of Raji cultures with EBV (HR-1), the abortively infected cells contain RNA encoded by at least 41% of EBV DNA. The polyadenylated RNA of superinfected Raji cells is enriched for a class of EBV RNA encoded by approximately 20% of EBV HR-1 DNA. Summation hybridization experiments suggest that the polyadenylated RNA in superinfected Raji cells is encoded by the same DNA sequences as encode RNA present in Raji cells before superinfection, most of which is not polyadenylated. That the same EBV RNA sequences are present in the polyadenylated and polyribosomal fractions of two independently derived, restringently infected cell lines suggests that these RNAs may specify functions related to maintenance of the transformed state. The complexity of this class of RNA is adequate to specify a sequence of a least 5,000 amino acids. That only some RNA species are polyadenylated in restringent and abortive infection suggests that polyadenylation or whatever determines polyadenylation may play a role in  the restricted expression of the EVB genome.", "contents": "Epstein-barr virus-specific RNA. II. Analysis of polyadenylated viral RNA in restringent, abortive, and prooductive infections. The complexity and abundance of Epstein-Barr (EBV)-specific RNA in cell cultures restringently, abortively, and productively infected with EBV has been analyed by hybridization of the infected cell RNA with purified viral DNA. The data indicate the following. (i) Cultures containing productively infected cells contain viral RNA encoded by at least 45% of EBV DNA, and almost all of the species of viral RNA are present in the polyadenylated and polyribosomal RNA fractions. (ii) Restringently infected Namalwa and Raji cultures, which contain only intranuclear antigen, EBNA, and enhanced capacity for growth in vitro, contain EBV RNA encoded by at least 16 and 30% of the EBV DNA, respectively. The polyadenylated and polyribosomal RNA fractions of Raji and Namalwa cells are enriched for a class of EBV RNA encoded by approximately 5% of EBV DNA. The same EBV DNA sequences encode the polyadenylated and polyribosomal RNA of both Raji and Namalwa cells. (iii) After superinfection of Raji cultures with EBV (HR-1), the abortively infected cells contain RNA encoded by at least 41% of EBV DNA. The polyadenylated RNA of superinfected Raji cells is enriched for a class of EBV RNA encoded by approximately 20% of EBV HR-1 DNA. Summation hybridization experiments suggest that the polyadenylated RNA in superinfected Raji cells is encoded by the same DNA sequences as encode RNA present in Raji cells before superinfection, most of which is not polyadenylated. That the same EBV RNA sequences are present in the polyadenylated and polyribosomal fractions of two independently derived, restringently infected cell lines suggests that these RNAs may specify functions related to maintenance of the transformed state. The complexity of this class of RNA is adequate to specify a sequence of a least 5,000 amino acids. That only some RNA species are polyadenylated in restringent and abortive infection suggests that polyadenylation or whatever determines polyadenylation may play a role in  the restricted expression of the EVB genome."}
{"id": "PMID:194057", "title": "Increase in lipid fluidity of cellular membranes induced by adsorption of RNA and DNA virions.", "content": "Changes in the dynamic behavior of membrane lipids of mammalian cells induced by adsorption of animal viruses were quantitatively monitored by fluorescence polarization analysis with the aid of the fluorescent probe 1,6-diphenyl 1,3,5-hexatriene embedded in the surface membrane lipid core of intact cells. Adsorption of encephalomyocarditis, West Nile, and polyoma viruses to hamster (baby hamster kidney) and mouse (3T3) cells is accompanied by a rapid and significant increase in the degree of fluidity of membrane lipids of the infected cells. These changes in membrane fluidity, which are virus dose dependent, are inhibited by low temperature and by treatment of the cells before-hand with compounds known to block viral receptors on the cell surface. It is suggested that increase in membrane lipid fluidity, induced by the adsorption of virions, is an early event in the process of cell-virus interactions.", "contents": "Increase in lipid fluidity of cellular membranes induced by adsorption of RNA and DNA virions. Changes in the dynamic behavior of membrane lipids of mammalian cells induced by adsorption of animal viruses were quantitatively monitored by fluorescence polarization analysis with the aid of the fluorescent probe 1,6-diphenyl 1,3,5-hexatriene embedded in the surface membrane lipid core of intact cells. Adsorption of encephalomyocarditis, West Nile, and polyoma viruses to hamster (baby hamster kidney) and mouse (3T3) cells is accompanied by a rapid and significant increase in the degree of fluidity of membrane lipids of the infected cells. These changes in membrane fluidity, which are virus dose dependent, are inhibited by low temperature and by treatment of the cells before-hand with compounds known to block viral receptors on the cell surface. It is suggested that increase in membrane lipid fluidity, induced by the adsorption of virions, is an early event in the process of cell-virus interactions."}
{"id": "PMID:194058", "title": "Friend strain of spleen focus-forming virus: a recombinant between mouse type C ecotropic viral sequences and sequences related to xenotropic virus.", "content": "The genome of the Friend strain of the spleen focus-forming virus (SFFV) has been analyzed by molecular hybridization. SFFV is composed of genetic sequences homologous to Friend type C helper virus (F-MuLV) and SFFV-specific sequences not present in F-MuLV. These SFFV-specific sequences are present in both the Friend and Rauscher strains of murine erythroleukemia virus. The SFFV-specific sequences are partially homologous to three separate strains of mouse xenotropic virus but not to several cloned mouse ecotropic viruses. Thus, the Friend strain of SFFV appears to be a recombinant between a portion of the F-MuLV genome and RNA sequences that are highly related to murine xenotropic viruses. The implications of the acquisition of the xenotropic virus-related sequences are discussed in relation to the leukemogenicity of SFFV, and a model for the pathogenicity of other murine leukemia-inducing viruses is proposed.", "contents": "Friend strain of spleen focus-forming virus: a recombinant between mouse type C ecotropic viral sequences and sequences related to xenotropic virus. The genome of the Friend strain of the spleen focus-forming virus (SFFV) has been analyzed by molecular hybridization. SFFV is composed of genetic sequences homologous to Friend type C helper virus (F-MuLV) and SFFV-specific sequences not present in F-MuLV. These SFFV-specific sequences are present in both the Friend and Rauscher strains of murine erythroleukemia virus. The SFFV-specific sequences are partially homologous to three separate strains of mouse xenotropic virus but not to several cloned mouse ecotropic viruses. Thus, the Friend strain of SFFV appears to be a recombinant between a portion of the F-MuLV genome and RNA sequences that are highly related to murine xenotropic viruses. The implications of the acquisition of the xenotropic virus-related sequences are discussed in relation to the leukemogenicity of SFFV, and a model for the pathogenicity of other murine leukemia-inducing viruses is proposed."}
{"id": "PMID:194059", "title": "Circular Epstein-Barr virus genomes of reduced size in a human lymphoid cell line of infectious mononucleosis origin.", "content": "Circular Epstein-Barr virus (EBV) DNA molecules have been purified and characterized from a human lymphoid cell line derived from a case of heterophile antibody-positive, blood transfusion-induced infectious mononucleosis, 883L. The circular EBV DNA in three cell lines obtained by transformation of human umbilical cord blood leukocytes with a strain of EBV originally derived from 883L was also studied. As estimated from sedimentation velocity data and electron microscopy, the circular EBV DNA molecules are 10 to 15% smaller than either the circular EBV DNA previously found intracellularly in several other types of EBV-transformed cells or the linear EBV DNA present extracellularly in virus particles. In addition, the EBV-transformed cord blood cell lines studied here differed from other EBV-transformed cells in that integrated virus DNA sequences could not be detected.", "contents": "Circular Epstein-Barr virus genomes of reduced size in a human lymphoid cell line of infectious mononucleosis origin. Circular Epstein-Barr virus (EBV) DNA molecules have been purified and characterized from a human lymphoid cell line derived from a case of heterophile antibody-positive, blood transfusion-induced infectious mononucleosis, 883L. The circular EBV DNA in three cell lines obtained by transformation of human umbilical cord blood leukocytes with a strain of EBV originally derived from 883L was also studied. As estimated from sedimentation velocity data and electron microscopy, the circular EBV DNA molecules are 10 to 15% smaller than either the circular EBV DNA previously found intracellularly in several other types of EBV-transformed cells or the linear EBV DNA present extracellularly in virus particles. In addition, the EBV-transformed cord blood cell lines studied here differed from other EBV-transformed cells in that integrated virus DNA sequences could not be detected."}
{"id": "PMID:194060", "title": "Temperature-dependent host range mutation in vesicular stomatitis virus affecting polypeptide L.", "content": "We established previously that the temperature-dependent host range mutant, td CE 3, of vesicular stomatitis virus (VSV) New Jersey possesses temperature-sensitive RNA transcriptase activity. In this paper, we describe dissociation and reconstitution experiments designed to determine which VSV polypeptide is affected by the td CE 3 mutation. Wild-type VSV New Jersey (ts+), the temperature-dependent host range mutant (td CE 3), and the revertant of this mutant (td CE/R1) were used. Transcribing nucleoprotein preparations, isolated from purified virus particles, were treated in the presence of digitonin with either 0.9 M LiCl to produce supernatants containing virtually only the L polypeptide or 2.0 M LiCl to produce ribonucleoprotein pellets containing only the polypeptides N and NS. Supernatant and pellet fractions synthesized either no or only trace amounts of RNA in vitro. Reconstitution of the supernatants with the pellets in all combinations at 31 degrees C restored much of the transcriptase activity of the transcribing nucleoprotein preparations. RNA synthesis occurred at 39 degrees C when the three pellets were reconstituted with wild-type and revertant supernatants. However, supernatant of the mutant td CE 3 reconstituted with any of the three pellets resulted in little or no detectable transcriptase activity at 39 degrees C. This implies that the polypeptide affected by the td CE 3 mutation is the L polypeptide.", "contents": "Temperature-dependent host range mutation in vesicular stomatitis virus affecting polypeptide L. We established previously that the temperature-dependent host range mutant, td CE 3, of vesicular stomatitis virus (VSV) New Jersey possesses temperature-sensitive RNA transcriptase activity. In this paper, we describe dissociation and reconstitution experiments designed to determine which VSV polypeptide is affected by the td CE 3 mutation. Wild-type VSV New Jersey (ts+), the temperature-dependent host range mutant (td CE 3), and the revertant of this mutant (td CE/R1) were used. Transcribing nucleoprotein preparations, isolated from purified virus particles, were treated in the presence of digitonin with either 0.9 M LiCl to produce supernatants containing virtually only the L polypeptide or 2.0 M LiCl to produce ribonucleoprotein pellets containing only the polypeptides N and NS. Supernatant and pellet fractions synthesized either no or only trace amounts of RNA in vitro. Reconstitution of the supernatants with the pellets in all combinations at 31 degrees C restored much of the transcriptase activity of the transcribing nucleoprotein preparations. RNA synthesis occurred at 39 degrees C when the three pellets were reconstituted with wild-type and revertant supernatants. However, supernatant of the mutant td CE 3 reconstituted with any of the three pellets resulted in little or no detectable transcriptase activity at 39 degrees C. This implies that the polypeptide affected by the td CE 3 mutation is the L polypeptide."}
{"id": "PMID:194061", "title": "Specificity of initiation of transcription of simian virus 40 DNA I by Escherichia coli RNA polymerase: identification and localization of five sites for initiation with [gamma-32P]ATP.", "content": "Simian virus 40 (SV40) DNA I was transcribed with Escherichia coli RNA polymerase in the presence of gamma-32P-labeled ribonucleoside triphosphates in order to investigate the specificity of initiation of in vitro transcription. ATP and GTP served as predominant initiating nucleotides, the former being incorporated about twice as much as the latter. Cleavage of [gamma-32P]ATP-labeled SV40 complementary RNA (cRNA) with T1 RNase followed by homochromatographic analysis of the resultant 5' initiation fragments revealed the presence of four specific initiation fragments 6 to 9 nucleotides in length, designated AI, AII, AIIIa, and AIIIb. By means of hybridization of [gamma-32P]ATP-labeled SV40 cRNA to DNA from specific adenovirus 2-SV40 hybrids and specific restriction endonuclease fragments of SV40 DNA before chromatographic analysis, it was possible to identify and determine approximate localizations of five [gamma-32P]ATP initiation sites on the SV40 genome: one in Hin-G close to the Hin-G-B junction, giving rise to the AII fragment, two in the overalpping fragment Hin-A-Hae-A,giving rise to AI and AIII fragments, and two in the fragment Hin-A-Hae-E, also giving rise to AI and AIII fragments. All five sites either fall within or lie near regions of the genome that are cleaved by S1 nuclease and subject to partial alkaline denaturation. These five sites lie on the minus strand of SV40 DNA and initiate RNAs that are copied in a leftward direction. Cleavage of [gamma-32P]GTP-labeled cRNA with pancreatic RNase liberated three major 5' initiation fragments of short length, GI, GII, and GIII, suggesting the presence of three principal GTP initiation sites.", "contents": "Specificity of initiation of transcription of simian virus 40 DNA I by Escherichia coli RNA polymerase: identification and localization of five sites for initiation with [gamma-32P]ATP. Simian virus 40 (SV40) DNA I was transcribed with Escherichia coli RNA polymerase in the presence of gamma-32P-labeled ribonucleoside triphosphates in order to investigate the specificity of initiation of in vitro transcription. ATP and GTP served as predominant initiating nucleotides, the former being incorporated about twice as much as the latter. Cleavage of [gamma-32P]ATP-labeled SV40 complementary RNA (cRNA) with T1 RNase followed by homochromatographic analysis of the resultant 5' initiation fragments revealed the presence of four specific initiation fragments 6 to 9 nucleotides in length, designated AI, AII, AIIIa, and AIIIb. By means of hybridization of [gamma-32P]ATP-labeled SV40 cRNA to DNA from specific adenovirus 2-SV40 hybrids and specific restriction endonuclease fragments of SV40 DNA before chromatographic analysis, it was possible to identify and determine approximate localizations of five [gamma-32P]ATP initiation sites on the SV40 genome: one in Hin-G close to the Hin-G-B junction, giving rise to the AII fragment, two in the overalpping fragment Hin-A-Hae-A,giving rise to AI and AIII fragments, and two in the fragment Hin-A-Hae-E, also giving rise to AI and AIII fragments. All five sites either fall within or lie near regions of the genome that are cleaved by S1 nuclease and subject to partial alkaline denaturation. These five sites lie on the minus strand of SV40 DNA and initiate RNAs that are copied in a leftward direction. Cleavage of [gamma-32P]GTP-labeled cRNA with pancreatic RNase liberated three major 5' initiation fragments of short length, GI, GII, and GIII, suggesting the presence of three principal GTP initiation sites."}
{"id": "PMID:194062", "title": "Changes in synthesis of DNA-binding proteins during the onset of transformation in NRK cells transformed by a temperature-sensitive mutant of Rous sarcoma virus.", "content": "Synthesis of cytoplasmic DNA-binding proteins was investigated after a shift from the nonpermissive to the permissive temperature in NRK cells transformed by a temperature-sensitive mutant of Rous sarcoma virus [ts339(RSV)]. Cells were labeled for several generations in [3H]leucine and were pulse-labeled with [35S]methionine for 1 h at the nonpermissive temperature (39 degrees C) and at the permissive temperature (33 degrees C, 5 h after shift from 39 degrees C). Proteins binding to sequential columns of double-stranded and single-stranded DNA-cellulose were examined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and the 35S/3H ratios were obtained for each column fraction and for individual polypeptides. The protein fractions binding to single-stranded, but not double-stranded, DNA and eluting at high salt concentrations (greater than 0.60 M NaCl) showed elevated 35S/3H ratios. This indicated increased synthesis of these proteins within 5 h after the onset of transformation. The majority of the polypeptides in these fractions showed increased synthesis as a consequence of transformation. One prominent polypeptide among them constituted 0.1% of the cytosol protein and had a molecular weight of 93,000. We conclude that the synthesis of proteins binding tightly to single-stranded DNA is increased early after the onset of transformation.", "contents": "Changes in synthesis of DNA-binding proteins during the onset of transformation in NRK cells transformed by a temperature-sensitive mutant of Rous sarcoma virus. Synthesis of cytoplasmic DNA-binding proteins was investigated after a shift from the nonpermissive to the permissive temperature in NRK cells transformed by a temperature-sensitive mutant of Rous sarcoma virus [ts339(RSV)]. Cells were labeled for several generations in [3H]leucine and were pulse-labeled with [35S]methionine for 1 h at the nonpermissive temperature (39 degrees C) and at the permissive temperature (33 degrees C, 5 h after shift from 39 degrees C). Proteins binding to sequential columns of double-stranded and single-stranded DNA-cellulose were examined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and the 35S/3H ratios were obtained for each column fraction and for individual polypeptides. The protein fractions binding to single-stranded, but not double-stranded, DNA and eluting at high salt concentrations (greater than 0.60 M NaCl) showed elevated 35S/3H ratios. This indicated increased synthesis of these proteins within 5 h after the onset of transformation. The majority of the polypeptides in these fractions showed increased synthesis as a consequence of transformation. One prominent polypeptide among them constituted 0.1% of the cytosol protein and had a molecular weight of 93,000. We conclude that the synthesis of proteins binding tightly to single-stranded DNA is increased early after the onset of transformation."}
{"id": "PMID:194063", "title": "Spatial relationships of the proteins of vesicular stomatitis virus: induction of reversible oligomers by cleavable protein cross-linkers and oxidation.", "content": "To delineate the proximity and spatial arrangement of the major structural proteins of intact vesicular stomatitis (VS) virions, protein complexes formed by oxidation or by bivalent cross-linkers were analyzed by two-dimensional electrophoresis on polyacrylamide slab gels. H2O2 oxidation of VS virions produced an N-polypeptide dimer (molecular weight, approximately equal to 110,000) on a first dimension gel that could be reduced to N monomers (molecular weight, approximately equal to 50,000). Proteins extracted from unreduced and unoxidized VS virions contained dimeric and trimeric forms of M-protein complexes as well as a heterodimer of M and N protein. Qualitatively similar VS viral protein complexes were generated by exposing VS virions to the reversible protein cross-linkers methyl-4-mercaptobutyrimidate (MMB), tartryl diazide (TDA), and dithiobis(succinimidyl proprionate) (DTBSP); cross-linked complexes on first-dimension gels were cleaved by reduction with 2-mercaptoethanol (MMB or DTBSP cross-linked) or by periodate oxidation (TDA cross-linked). In addition to covalently linked homodiamers of M and N proteins and a protein M-N heterodimer, the protein cross-linkers also generated homo-oligomers of G protein and a G-M heterodimer. These data suggest that the glycoprotein spike of VS virus is composed of more than one G protein. The existence of N-M and G-M heterodimers is consistent with the hypothesis that the matrix (M) protein may serve as a bridge between the G and N proteins in assembly of the VS virion.", "contents": "Spatial relationships of the proteins of vesicular stomatitis virus: induction of reversible oligomers by cleavable protein cross-linkers and oxidation. To delineate the proximity and spatial arrangement of the major structural proteins of intact vesicular stomatitis (VS) virions, protein complexes formed by oxidation or by bivalent cross-linkers were analyzed by two-dimensional electrophoresis on polyacrylamide slab gels. H2O2 oxidation of VS virions produced an N-polypeptide dimer (molecular weight, approximately equal to 110,000) on a first dimension gel that could be reduced to N monomers (molecular weight, approximately equal to 50,000). Proteins extracted from unreduced and unoxidized VS virions contained dimeric and trimeric forms of M-protein complexes as well as a heterodimer of M and N protein. Qualitatively similar VS viral protein complexes were generated by exposing VS virions to the reversible protein cross-linkers methyl-4-mercaptobutyrimidate (MMB), tartryl diazide (TDA), and dithiobis(succinimidyl proprionate) (DTBSP); cross-linked complexes on first-dimension gels were cleaved by reduction with 2-mercaptoethanol (MMB or DTBSP cross-linked) or by periodate oxidation (TDA cross-linked). In addition to covalently linked homodiamers of M and N proteins and a protein M-N heterodimer, the protein cross-linkers also generated homo-oligomers of G protein and a G-M heterodimer. These data suggest that the glycoprotein spike of VS virus is composed of more than one G protein. The existence of N-M and G-M heterodimers is consistent with the hypothesis that the matrix (M) protein may serve as a bridge between the G and N proteins in assembly of the VS virion."}
{"id": "PMID:194064", "title": "Inclusion body disease of falcons (Herpesvirus infection) in an American kestrel.", "content": "Postmortem examination of a captive-bred American kestrel (Falco sparverius) showed numerous white necrotic foci 1-2 mm in diameter throughout the liver and spleen. The results of light and spleen. The results of light and electron microscopic studies and experimental transmission to a captive American kestrel and a barred owl (Strix varia) suggests a herpesvirus similar to those dsecribed for owls and other falcons in the U.S. This is the first report of a naturally occurring case of inclusion body disease of falcons in the American kestrel.", "contents": "Inclusion body disease of falcons (Herpesvirus infection) in an American kestrel. Postmortem examination of a captive-bred American kestrel (Falco sparverius) showed numerous white necrotic foci 1-2 mm in diameter throughout the liver and spleen. The results of light and spleen. The results of light and electron microscopic studies and experimental transmission to a captive American kestrel and a barred owl (Strix varia) suggests a herpesvirus similar to those dsecribed for owls and other falcons in the U.S. This is the first report of a naturally occurring case of inclusion body disease of falcons in the American kestrel."}
{"id": "PMID:194065", "title": "Demeclocycline. Treatment for syndrome of inappropriate antidiuretic hormone secretion.", "content": "The efficacy of demeclocycline hydrochloride in suppressing the tubular action of tumoral antidiuretic products was tested in seven patients with the syndrome of inappropriate antidiuretic hormone secretion. In all patients, demeclocycline hydrochloride (1,200 mg/day) induced production of hypotonic urine and corrected hyponatremia despite large fluid intakes. Comparison of the response to a standard water load before and during treatment showed a notable improvement in the response to water ingestion. Even though demeclocycline moderately impairs renal function, it appears to be the treatment of choice in the chronic form of the syndrome.", "contents": "Demeclocycline. Treatment for syndrome of inappropriate antidiuretic hormone secretion. The efficacy of demeclocycline hydrochloride in suppressing the tubular action of tumoral antidiuretic products was tested in seven patients with the syndrome of inappropriate antidiuretic hormone secretion. In all patients, demeclocycline hydrochloride (1,200 mg/day) induced production of hypotonic urine and corrected hyponatremia despite large fluid intakes. Comparison of the response to a standard water load before and during treatment showed a notable improvement in the response to water ingestion. Even though demeclocycline moderately impairs renal function, it appears to be the treatment of choice in the chronic form of the syndrome."}
{"id": "PMID:194066", "title": "Modern day menstrual folklore. Some clinical implications.", "content": "Clinicians are often unaware of the folk medical beliefs of their patients or consider them to be harmless and unimportant. Such beliefs are instrumental in shaping patient behavior, however, and may contribute to negative health practices. The information presented here demonstrates that attitudes toward a single bodily function, menstruation, may adversely affect women's body image, perception of disease causation, diet, willingness to take medication, contraceptive use, and the ability to plan pregnancies. The data are part of a pilot study in which patients in a clinic serving a multiethnic low-income population were questioned about their knowledge and beliefs concerning the female reproductive cycle. It is concluded that health personnel should strive to learn what women know and believe about their bodies and how they function, to improve health care provision.", "contents": "Modern day menstrual folklore. Some clinical implications. Clinicians are often unaware of the folk medical beliefs of their patients or consider them to be harmless and unimportant. Such beliefs are instrumental in shaping patient behavior, however, and may contribute to negative health practices. The information presented here demonstrates that attitudes toward a single bodily function, menstruation, may adversely affect women's body image, perception of disease causation, diet, willingness to take medication, contraceptive use, and the ability to plan pregnancies. The data are part of a pilot study in which patients in a clinic serving a multiethnic low-income population were questioned about their knowledge and beliefs concerning the female reproductive cycle. It is concluded that health personnel should strive to learn what women know and believe about their bodies and how they function, to improve health care provision."}
{"id": "PMID:194069", "title": "Lung carcinoma in young adults.", "content": "Twenty-four patients less than 40 years of age were diagnosed at Walter Red Army Medical Center between 1971 and 1976 as having lung cancer. The youngest patient was 19 years old. Only one was a nonsmoker. Most patients were symptomatic at the time of examination. The chest roentgenogram showed an infiltrate or consolidation in 9, a mass lesion in 13, and a pleural effusion in 1. Thirty-eight percent had adenocarcinoma, 21% had squamous cell carcinoma, and 21% large cell carcinoma. Nineteen patients had stage II or III disease at the time of initial examination, and only six had resectable tumors. Survival rates were poor.", "contents": "Lung carcinoma in young adults. Twenty-four patients less than 40 years of age were diagnosed at Walter Red Army Medical Center between 1971 and 1976 as having lung cancer. The youngest patient was 19 years old. Only one was a nonsmoker. Most patients were symptomatic at the time of examination. The chest roentgenogram showed an infiltrate or consolidation in 9, a mass lesion in 13, and a pleural effusion in 1. Thirty-eight percent had adenocarcinoma, 21% had squamous cell carcinoma, and 21% large cell carcinoma. Nineteen patients had stage II or III disease at the time of initial examination, and only six had resectable tumors. Survival rates were poor."}
{"id": "PMID:194073", "title": "Age-dependent response of mice to a mouse hepatitis virus, MHV-S.", "content": "To a mouse hepatitis virus strain MHV-S, 4 week-old ICR mice were shown to be fully resistant irrespective of route and dose of inoculation, and fatal infection was produced only with cortisone treatment. Two-week-old mice also showed high resistance to MHV-S except for after intracerebral inoculation, and 60% of infected mice died. Mice aged 1 week or less, however, died after intracerebral, intraperitoneal, subcutaneous and intranasal inoculation, while some of them survived after peroral inoculation. Between mice aged 4 weeks and those aged 1 week or less, there was a significant difference in viral growth in the liver after intranasal inoculation, whereas almost the same degree of viral multiplication was seen in the brain of both age groups. Such age-dependent difference in susceptibility to a low-virulent mouse hepatitis virus especially after nasal inoculation is discussed in relation to natural infection in mouse breeding colonies.", "contents": "Age-dependent response of mice to a mouse hepatitis virus, MHV-S. To a mouse hepatitis virus strain MHV-S, 4 week-old ICR mice were shown to be fully resistant irrespective of route and dose of inoculation, and fatal infection was produced only with cortisone treatment. Two-week-old mice also showed high resistance to MHV-S except for after intracerebral inoculation, and 60% of infected mice died. Mice aged 1 week or less, however, died after intracerebral, intraperitoneal, subcutaneous and intranasal inoculation, while some of them survived after peroral inoculation. Between mice aged 4 weeks and those aged 1 week or less, there was a significant difference in viral growth in the liver after intranasal inoculation, whereas almost the same degree of viral multiplication was seen in the brain of both age groups. Such age-dependent difference in susceptibility to a low-virulent mouse hepatitis virus especially after nasal inoculation is discussed in relation to natural infection in mouse breeding colonies."}
{"id": "PMID:194076", "title": "Action of 5-hydroxytryptamine on isolated spinal cord of bullfrogs.", "content": "Slow depolarizations of dorsal root nerve terminals and motoneurons, which were produced by 5-hydroxytryptamine (5-HT) applied directly to isolated bullfrog spinal cords, were recorded by the sucrose-gap method. These depolarizations were eliminated in the Ca-deficient Ringer's solution containing Mg, suggesting that these 5-HT depolarizations were not caused by a direct action of 5-HT on dorsal root nerve terminals or motoneurons but rather by actions of transmitters released from interneurons. Indeed, mephenesin, which is a selective blocker of polysynaptic transmission in the spinal cord, inhibited more markedly the 5-HT depolarization than the L-glutamate or GABA depolarization. The transmitter directly responsible for the generation of the 5-HT depolarization of dorsal root nerve terminals was not considered to be GABA as the 5-HT depolarization was not antagonized by picrotoxin. It would thus appear that 5-HT stimulates interneurons in the amphibian spinal cord and unknown transmitters released from these interneurons depolarize the dorsal root nerve terminals.", "contents": "Action of 5-hydroxytryptamine on isolated spinal cord of bullfrogs. Slow depolarizations of dorsal root nerve terminals and motoneurons, which were produced by 5-hydroxytryptamine (5-HT) applied directly to isolated bullfrog spinal cords, were recorded by the sucrose-gap method. These depolarizations were eliminated in the Ca-deficient Ringer's solution containing Mg, suggesting that these 5-HT depolarizations were not caused by a direct action of 5-HT on dorsal root nerve terminals or motoneurons but rather by actions of transmitters released from interneurons. Indeed, mephenesin, which is a selective blocker of polysynaptic transmission in the spinal cord, inhibited more markedly the 5-HT depolarization than the L-glutamate or GABA depolarization. The transmitter directly responsible for the generation of the 5-HT depolarization of dorsal root nerve terminals was not considered to be GABA as the 5-HT depolarization was not antagonized by picrotoxin. It would thus appear that 5-HT stimulates interneurons in the amphibian spinal cord and unknown transmitters released from these interneurons depolarize the dorsal root nerve terminals."}
{"id": "PMID:194077", "title": "Phosphodiesterase inhibitors: their comparative effectiveness in vitro in various organs.", "content": "The inhibitor constants of several inhibitors for cyclic AMP- and cyclic GMP-phosphodiesterase from various organs are compared. The inhibitors were classical theophyline, papaverine, and some of newly developed inhibitors: an imidazolidinone compound, RO20-1724, and two phthalazinol compounds, EG 467 and EG 626. Among the inhibitors tested, papaverine and EG 626 were found to be the most potent. Both compounds were extremely inhibitory to platelet and arterial phosphodiesterases. EG 626 was much more inhibitory to cyclic AMP phosphodiesterase than to cyclic GMP phosphodiesterase in platelet- and brain-extract and RO20-1724 was inhibitory to cyclic AMP- but not cyclic GMP-phosphodiesterase in brain-extract. When the skin adenyl cyclase was activated by AMP, the addition of theophylline blocked this activation, but EG 626 or EG 467 further potentiated the activation. These in vitro studies may serve as basic screening tests for the effectiveness of the specific phosphodiesterase inhibitors.", "contents": "Phosphodiesterase inhibitors: their comparative effectiveness in vitro in various organs. The inhibitor constants of several inhibitors for cyclic AMP- and cyclic GMP-phosphodiesterase from various organs are compared. The inhibitors were classical theophyline, papaverine, and some of newly developed inhibitors: an imidazolidinone compound, RO20-1724, and two phthalazinol compounds, EG 467 and EG 626. Among the inhibitors tested, papaverine and EG 626 were found to be the most potent. Both compounds were extremely inhibitory to platelet and arterial phosphodiesterases. EG 626 was much more inhibitory to cyclic AMP phosphodiesterase than to cyclic GMP phosphodiesterase in platelet- and brain-extract and RO20-1724 was inhibitory to cyclic AMP- but not cyclic GMP-phosphodiesterase in brain-extract. When the skin adenyl cyclase was activated by AMP, the addition of theophylline blocked this activation, but EG 626 or EG 467 further potentiated the activation. These in vitro studies may serve as basic screening tests for the effectiveness of the specific phosphodiesterase inhibitors."}
{"id": "PMID:194082", "title": "Breast carcinoma, thyroid carcinoma, and T3 thyrotoxicosis in a male cretin.", "content": "A male patient with clinical and radiographic evidence of cretinism was found to have T3 thyrotoxicosis. The cause was thought to be a well-differentiated follicular carcinoma of the thyroid. Although the disease was not documented, the patient probably had long-standing hypothyroidism. Untreated primary thyroid failure accompanied by high serum thyroid stimulating hormone (TSH) may be carcinogenic to the thyroid. The association of thyroid abnormalities and male breast carcinoma is discussed.", "contents": "Breast carcinoma, thyroid carcinoma, and T3 thyrotoxicosis in a male cretin. A male patient with clinical and radiographic evidence of cretinism was found to have T3 thyrotoxicosis. The cause was thought to be a well-differentiated follicular carcinoma of the thyroid. Although the disease was not documented, the patient probably had long-standing hypothyroidism. Untreated primary thyroid failure accompanied by high serum thyroid stimulating hormone (TSH) may be carcinogenic to the thyroid. The association of thyroid abnormalities and male breast carcinoma is discussed."}
{"id": "PMID:194109", "title": "The cellular lesions of Farber's disease and their experimental reproduction in tissue culture.", "content": "In a case of Farber's disease, lysosomal inclusions were shown to contain lamellar, rectilinear, or curvilinear material. In tissue culture, when fibroblasts from the patient were overloaded with ceramides containing nonhydroxylated fatty acids a lysosomal accumulation of small curvilinear structures identical with those observed at autopsy were seen. These inclusions persisted for several weeks after the cells were replaced in a normal culture medium. Normal fibroblasts overloaded in the same experimental conditions showed identical, although less numerous, lysosomal inclusions, which disappeared rapidly in a ceramide-free culture medium. No inclusions were found after overloading normal or pathologic fibroblasts with ceramides containing hydroxylated fatty acids.", "contents": "The cellular lesions of Farber's disease and their experimental reproduction in tissue culture. In a case of Farber's disease, lysosomal inclusions were shown to contain lamellar, rectilinear, or curvilinear material. In tissue culture, when fibroblasts from the patient were overloaded with ceramides containing nonhydroxylated fatty acids a lysosomal accumulation of small curvilinear structures identical with those observed at autopsy were seen. These inclusions persisted for several weeks after the cells were replaced in a normal culture medium. Normal fibroblasts overloaded in the same experimental conditions showed identical, although less numerous, lysosomal inclusions, which disappeared rapidly in a ceramide-free culture medium. No inclusions were found after overloading normal or pathologic fibroblasts with ceramides containing hydroxylated fatty acids."}
{"id": "PMID:194110", "title": "Arginine-rich cationic proteins of human eosinophil granules: comparison of the constituents of eosinophilic and neutrophilic leukocytes.", "content": "Several arginine-rich cationic proteins previously isolated from granules of leukemic myeloid cells have been found to reside primarily in human eosinophil leukocytes. The major component has a molecular weight of 21,000 and it contains approximately 2.6 moles of zinc per mole of protein. Velocity centrifugation of cytoplasm from leukocytes of patients with marked eosinophilia showed that this group of proteins is packaged in the crystalloid-containing large eosinophil granules. Approximately 30% of the protein content of eosinophil granules belonged to this group of cationic proteins. Bactericidal or esterolytic activities of the cationic proteins were not detected, nor did they inhibit guinea pig anaphylatoxin or histamine-induced contraction. The basic protein previously demonstrated in guinea pig eosinophils may be analogous to the group of basic proteins of human eosinophils but great differences are found for molecular weight and amino acid composition.", "contents": "Arginine-rich cationic proteins of human eosinophil granules: comparison of the constituents of eosinophilic and neutrophilic leukocytes. Several arginine-rich cationic proteins previously isolated from granules of leukemic myeloid cells have been found to reside primarily in human eosinophil leukocytes. The major component has a molecular weight of 21,000 and it contains approximately 2.6 moles of zinc per mole of protein. Velocity centrifugation of cytoplasm from leukocytes of patients with marked eosinophilia showed that this group of proteins is packaged in the crystalloid-containing large eosinophil granules. Approximately 30% of the protein content of eosinophil granules belonged to this group of cationic proteins. Bactericidal or esterolytic activities of the cationic proteins were not detected, nor did they inhibit guinea pig anaphylatoxin or histamine-induced contraction. The basic protein previously demonstrated in guinea pig eosinophils may be analogous to the group of basic proteins of human eosinophils but great differences are found for molecular weight and amino acid composition."}
{"id": "PMID:194111", "title": "Metabolism of kinins and angiotensins in the isolated glomerulus and brush border of rat kidney.", "content": "In order to localize the activities of kallikrein, kininase, angiotensin I converting enzyme, and angiotensinase in the kidney, rat kidneys were homogenized and glomeruli and brush border were isolated. The yield and purity of glomeruli preparations were high. The similarity of the structure of the isolated glomeruli in situ was established by scanning and transmission electron microscopy and freeze-fracture. The morphology of isolated brush border of proximal tubules was compared to brush border in situ. Isolated brush border, devoid of core material, retained its converting enzyme, kininase, and angiotensinase activity confirming our previous findings that these enzymes are bound to plasma membrane. Isolated glomeruli contained little or no kallikrein. In addition, compared to renal brush border, renal glomeruli contained a relatively low concentration of kininase, angiotensin I converting enzyme, and angiotensinase. The results of these experiments support the idea that the brush border of the proximal tubule is the major site of inactivation of kinins and angiotensins and that renal kallikrein enters the tubular filtrate distal to the glomeruli and proximal tubule.", "contents": "Metabolism of kinins and angiotensins in the isolated glomerulus and brush border of rat kidney. In order to localize the activities of kallikrein, kininase, angiotensin I converting enzyme, and angiotensinase in the kidney, rat kidneys were homogenized and glomeruli and brush border were isolated. The yield and purity of glomeruli preparations were high. The similarity of the structure of the isolated glomeruli in situ was established by scanning and transmission electron microscopy and freeze-fracture. The morphology of isolated brush border of proximal tubules was compared to brush border in situ. Isolated brush border, devoid of core material, retained its converting enzyme, kininase, and angiotensinase activity confirming our previous findings that these enzymes are bound to plasma membrane. Isolated glomeruli contained little or no kallikrein. In addition, compared to renal brush border, renal glomeruli contained a relatively low concentration of kininase, angiotensin I converting enzyme, and angiotensinase. The results of these experiments support the idea that the brush border of the proximal tubule is the major site of inactivation of kinins and angiotensins and that renal kallikrein enters the tubular filtrate distal to the glomeruli and proximal tubule."}
{"id": "PMID:194112", "title": "Induction of brain tumors in hamsters with BK virus, a human papovavirus.", "content": "The oncogenicity of BK virus for the central nervous system was studied in newborn hamsters. The virus was weakly oncogenic after intracerebral inoculation. Two of 45 hamsters treated with antithymocyte serum developed tumors whereas no untreated hamsters developed tumors. Both tumors were choroid plexus papillomas by histologic and electron microscopic examination. Cells cultured from one tumor had growth characteristics of transformed cells and had intranuclear T antigen; but infectious virus could not be rescued. Cultured tumor cells were weakly oncogenic for hamsters, but theoncogenicity of these cells was enhanced when the recipient animals were treated with antithymocyte serum. The possible role of host immune response as a basis for the weak oncogenicity of BK virus is discussed.", "contents": "Induction of brain tumors in hamsters with BK virus, a human papovavirus. The oncogenicity of BK virus for the central nervous system was studied in newborn hamsters. The virus was weakly oncogenic after intracerebral inoculation. Two of 45 hamsters treated with antithymocyte serum developed tumors whereas no untreated hamsters developed tumors. Both tumors were choroid plexus papillomas by histologic and electron microscopic examination. Cells cultured from one tumor had growth characteristics of transformed cells and had intranuclear T antigen; but infectious virus could not be rescued. Cultured tumor cells were weakly oncogenic for hamsters, but theoncogenicity of these cells was enhanced when the recipient animals were treated with antithymocyte serum. The possible role of host immune response as a basis for the weak oncogenicity of BK virus is discussed."}
{"id": "PMID:194114", "title": "Prospects for the clinical use of exogenous interferon.", "content": "Sufficient quantities of human leukocyte interferon have become available for small-scale clinical studies during the past years. The present status of the interferon treatment of respiratory infections, herpes keratitis, hepatitis B, osteogenic sarcoma, and some other tumours is surveyed. The pharmaco-kinetic and toxicological data obtained are summarized. The first clinical experiments with human fibroblast interferon have also been started. The prospects for mass production of human interferons for clinical use are discussed briefly.", "contents": "Prospects for the clinical use of exogenous interferon. Sufficient quantities of human leukocyte interferon have become available for small-scale clinical studies during the past years. The present status of the interferon treatment of respiratory infections, herpes keratitis, hepatitis B, osteogenic sarcoma, and some other tumours is surveyed. The pharmaco-kinetic and toxicological data obtained are summarized. The first clinical experiments with human fibroblast interferon have also been started. The prospects for mass production of human interferons for clinical use are discussed briefly."}
{"id": "PMID:194115", "title": "Distribution of exogenous cyclic adenosine 3', 5'-monophosphate in rabbits and cats.", "content": "The appearance and disapperance of total radioactivity in plasma and cerebrospinal fluid (CSF) were studied after a single intravenous injection of tritium-labelled cyclic adenosine 3', 5'-monophosphate (cAMP) into rabbits and cats. The radioactivity was rapidly cleared both from plasma and relatively stable when compared to plasma cAMP level. Exogenous cAMP in plasma does not seen to distribute into CSF by a simple diffusion.", "contents": "Distribution of exogenous cyclic adenosine 3', 5'-monophosphate in rabbits and cats. The appearance and disapperance of total radioactivity in plasma and cerebrospinal fluid (CSF) were studied after a single intravenous injection of tritium-labelled cyclic adenosine 3', 5'-monophosphate (cAMP) into rabbits and cats. The radioactivity was rapidly cleared both from plasma and relatively stable when compared to plasma cAMP level. Exogenous cAMP in plasma does not seen to distribute into CSF by a simple diffusion."}
{"id": "PMID:194130", "title": "Tumors of the major salivary glands.", "content": "Tumors of the major salivary glands are reviewed according to classification, location, surgical procedure and end results. Our data of the incidence of benign and malignant tumors show that the most commonly involved area is the parotid gland and the most frequent is of the mixed variety. In the parotid region 80 percent are benign and 20 percent are malignant; whereas, in the submandibular gland, the malignant and benign tumors are equally distributed. The need for an extensive surgical attack and inclusion of contiguous structure is dictated by the nature of the malignant disease. The role of postoperative irradiation is discussed as is the indication for neck dissection. Management of the facial nerve, relative to malignant tumors of the parotid gland, is considered in detail.", "contents": "Tumors of the major salivary glands. Tumors of the major salivary glands are reviewed according to classification, location, surgical procedure and end results. Our data of the incidence of benign and malignant tumors show that the most commonly involved area is the parotid gland and the most frequent is of the mixed variety. In the parotid region 80 percent are benign and 20 percent are malignant; whereas, in the submandibular gland, the malignant and benign tumors are equally distributed. The need for an extensive surgical attack and inclusion of contiguous structure is dictated by the nature of the malignant disease. The role of postoperative irradiation is discussed as is the indication for neck dissection. Management of the facial nerve, relative to malignant tumors of the parotid gland, is considered in detail."}
{"id": "PMID:194134", "title": "Detection of poliovirus antigens and antibodies: microindirect haemagglutination and haemagglutination inhibition tests for poliovirus types I, II, and III.", "content": "Microtitre indirect haemagglutination (IHA) and IHA-inhibition (IHAI) procedures were adapted to determine the reactivities of type I, II, and III poliovirus antibodies and antigens. Glutaraldehyde-fixed sheep erythrocytes were sensitized for these tests with concentrated, partially purified preparations of type I, II, and III poliovirus. Antibody titres by IHA were generally 10 to 100 times greater than serum microneutralization (SN) titres. The SN and IHA reactivities of three kinds of sera were compared. Of these sera, virus type specific antibodies, in monospecific guinea pig sera one week after immunization and in sera from hyperimmunized horses, could be readily differentiated and measured; antibodies in human diagnostic specimens, however, showed some intertypic cross reactivity. Monovalent one-week immune guinea pig sera reacted specifically in the IHAI test to differentiate viruses, and could be used for virus typing and differentiating strains of poliovirus type III.", "contents": "Detection of poliovirus antigens and antibodies: microindirect haemagglutination and haemagglutination inhibition tests for poliovirus types I, II, and III. Microtitre indirect haemagglutination (IHA) and IHA-inhibition (IHAI) procedures were adapted to determine the reactivities of type I, II, and III poliovirus antibodies and antigens. Glutaraldehyde-fixed sheep erythrocytes were sensitized for these tests with concentrated, partially purified preparations of type I, II, and III poliovirus. Antibody titres by IHA were generally 10 to 100 times greater than serum microneutralization (SN) titres. The SN and IHA reactivities of three kinds of sera were compared. Of these sera, virus type specific antibodies, in monospecific guinea pig sera one week after immunization and in sera from hyperimmunized horses, could be readily differentiated and measured; antibodies in human diagnostic specimens, however, showed some intertypic cross reactivity. Monovalent one-week immune guinea pig sera reacted specifically in the IHAI test to differentiate viruses, and could be used for virus typing and differentiating strains of poliovirus type III."}
{"id": "PMID:194139", "title": "Control of the Production of orthophosphate repressible extracellular enzymes in Neurospora crassa.", "content": "The abilities of purine- and pyrimidine-requiring mutants to produce six orthophosphate repressible extracellular enzymes, alkaline phosphatase, 5'-nucleotidase, acid phosphatase, two nucleases and ribonuclease N1 were examined by culturing these mutants in low and high phosphate media containing nucleotide or nucleoside. All the purine requiring mutants produced significantly reduced amounts of alkaline phosphatase, 5'-nucleotidase, acid phosphatase, alkaline nuclease and acid nuclease ranging 0.5-4.2, 5.0-17.4, 25.0-100, 20.3-67.5 and 6.2-48.5%, respectively. Production of ribonuclease N1 was found to be rather stimulated (150-564%) in these mutants. Essentially the same results were obtained for pyrimidine requiring mutants. Among those mutants ad-2 and ad-9 showed relatively high enzyme producing activity. Especially the production of ribonuclease N1 in ad-2 and ad-9 ranged to 4.9- and 5.6-fold that in the wild type. Though nuc-1 mutant (A1) has no ability to produce all these six repressible enzymes, double mutants A1ad-2 and A1ad-9 produced a significant amount of ribonuclease N1 in low and high phosphate media and acid phosphatase in low phosphate media.", "contents": "Control of the Production of orthophosphate repressible extracellular enzymes in Neurospora crassa. The abilities of purine- and pyrimidine-requiring mutants to produce six orthophosphate repressible extracellular enzymes, alkaline phosphatase, 5'-nucleotidase, acid phosphatase, two nucleases and ribonuclease N1 were examined by culturing these mutants in low and high phosphate media containing nucleotide or nucleoside. All the purine requiring mutants produced significantly reduced amounts of alkaline phosphatase, 5'-nucleotidase, acid phosphatase, alkaline nuclease and acid nuclease ranging 0.5-4.2, 5.0-17.4, 25.0-100, 20.3-67.5 and 6.2-48.5%, respectively. Production of ribonuclease N1 was found to be rather stimulated (150-564%) in these mutants. Essentially the same results were obtained for pyrimidine requiring mutants. Among those mutants ad-2 and ad-9 showed relatively high enzyme producing activity. Especially the production of ribonuclease N1 in ad-2 and ad-9 ranged to 4.9- and 5.6-fold that in the wild type. Though nuc-1 mutant (A1) has no ability to produce all these six repressible enzymes, double mutants A1ad-2 and A1ad-9 produced a significant amount of ribonuclease N1 in low and high phosphate media and acid phosphatase in low phosphate media."}
{"id": "PMID:194140", "title": "Genetics of carbon catabolite repression in Saccharomycess cerevisiae: genes involved in the derepression process.", "content": "A recessive mutant cat1-1, wild type CAT1, was isolated in Saccharomyces cerevisiae. It did not grow on glycerol nor ferment maltose even with fully constitutive, glucose resistant maltase synthesis. It prevented derepression of isocitrate lyase, fructose-1,6-diphosphatase and maltase in a constitutive but glucose sensitive maltase mutant. Derepression of malate dehydrogenase was retarded and slowed down. Sucrose fermentation and invertase synthesis was not affected. Respiration was normal. From this mutant, two reverse mutants were isolated. One was recessive, acted as a suppressor of cat1-1 and was called cat2-1, wild type CAT2; the other was dominant and allelic to CAT1 and designated CAT1-2d and cat2-1 caused an earlier derepression of enzymes studied but did not affect the repressed nor the fully derepressed enzyme levels. CAT1-2d and cat2-1 did not show any additive effects. It is proposed that carbon catabolite repression acts in two ways. The direct way represses synthesis of sensitive enzymes, during growth on repressing carbon sources whereas the other way regulates the derepression process. After alleviation of carbon catabolite repression, gene CAT1 becomes active and prevents the activity of CAT2 which functions as a repressor of sensitive enzyme synthesis. The CAT2 gene product has to be eliminated before derepression can actually occur. The time required for this causes a delay in derepression after the depletion of a repressible carbon source. cat1-1 cannot block CAT2 activity and therefore, derepression is blocked. cat2-1 is inactive and derepression can start after carbon catabolite repression has ceased. CAT1-2d permanently active as a repressor of CAT2 and eliminates the delay in derepression.", "contents": "Genetics of carbon catabolite repression in Saccharomycess cerevisiae: genes involved in the derepression process. A recessive mutant cat1-1, wild type CAT1, was isolated in Saccharomyces cerevisiae. It did not grow on glycerol nor ferment maltose even with fully constitutive, glucose resistant maltase synthesis. It prevented derepression of isocitrate lyase, fructose-1,6-diphosphatase and maltase in a constitutive but glucose sensitive maltase mutant. Derepression of malate dehydrogenase was retarded and slowed down. Sucrose fermentation and invertase synthesis was not affected. Respiration was normal. From this mutant, two reverse mutants were isolated. One was recessive, acted as a suppressor of cat1-1 and was called cat2-1, wild type CAT2; the other was dominant and allelic to CAT1 and designated CAT1-2d and cat2-1 caused an earlier derepression of enzymes studied but did not affect the repressed nor the fully derepressed enzyme levels. CAT1-2d and cat2-1 did not show any additive effects. It is proposed that carbon catabolite repression acts in two ways. The direct way represses synthesis of sensitive enzymes, during growth on repressing carbon sources whereas the other way regulates the derepression process. After alleviation of carbon catabolite repression, gene CAT1 becomes active and prevents the activity of CAT2 which functions as a repressor of sensitive enzyme synthesis. The CAT2 gene product has to be eliminated before derepression can actually occur. The time required for this causes a delay in derepression after the depletion of a repressible carbon source. cat1-1 cannot block CAT2 activity and therefore, derepression is blocked. cat2-1 is inactive and derepression can start after carbon catabolite repression has ceased. CAT1-2d permanently active as a repressor of CAT2 and eliminates the delay in derepression."}
{"id": "PMID:194141", "title": "Comparative studies on the '5'-cap' and in vitro translational activity of cytoplasmic and nuclear poly A(+) RNA1.", "content": "The translational activities of cytoplasmic poly A(+)RNA of normal rat liver and Novikoff hepatoma cells in the wheat germ cell free system were found to be approximately 15-20 times greater than tose of the corresponding nuclear poly A(+) RNA. The translationsl activities were 85 and 62 pmoles 3H-leucine incorporated/micron g cytoglasmic poly A(+) RNA for the liver and tumor respectively and 3-4 pmoles 3H-leucine incoporated/micron g nuclear poly A(+)RNA. Inasmuch as intergity of the '5'-cap' of mRNA is essential for its translational activity, quantitative comparisons were made of its content in these RNA fractions. Of the total 32P incorporated into the tumor cytoplasmic poly A(+) RNA, 0.41% was in the '5'-cap'; in nuclear poly A(+) RNA, the '5'-cap' contained 0.11%. After periodate oxidation and labeling with KB3H4, m7 guanosine, the 5'-terminal nucleoside in both liver and Novikoff hepatoma nuclear poly A(+) RNA contained approximately 20% as much isotope as in the cytoplasmic poly A(+) RNA. These results suggest the lower translational activity of nuclear poly A(+) RNA is partly related to its lower content of the '5'-cap'. Molecular selection of poly A(+) RNA for transport out of the nucleus or further cytoplasmic processing may account for the higher percentage of the '5-cap' and the greater translational activity of the cytoplasmic poly A(+) RNA. During these studies, it was also found that the m7 guanosine of the '5'-cap' was not removed during translation of the mRNA in the wheat germ system; this result suggests that the '5'-cap' may associate with allosteric binding sites of initiation factor(s).", "contents": "Comparative studies on the '5'-cap' and in vitro translational activity of cytoplasmic and nuclear poly A(+) RNA1. The translational activities of cytoplasmic poly A(+)RNA of normal rat liver and Novikoff hepatoma cells in the wheat germ cell free system were found to be approximately 15-20 times greater than tose of the corresponding nuclear poly A(+) RNA. The translationsl activities were 85 and 62 pmoles 3H-leucine incorporated/micron g cytoglasmic poly A(+) RNA for the liver and tumor respectively and 3-4 pmoles 3H-leucine incoporated/micron g nuclear poly A(+)RNA. Inasmuch as intergity of the '5'-cap' of mRNA is essential for its translational activity, quantitative comparisons were made of its content in these RNA fractions. Of the total 32P incorporated into the tumor cytoplasmic poly A(+) RNA, 0.41% was in the '5'-cap'; in nuclear poly A(+) RNA, the '5'-cap' contained 0.11%. After periodate oxidation and labeling with KB3H4, m7 guanosine, the 5'-terminal nucleoside in both liver and Novikoff hepatoma nuclear poly A(+) RNA contained approximately 20% as much isotope as in the cytoplasmic poly A(+) RNA. These results suggest the lower translational activity of nuclear poly A(+) RNA is partly related to its lower content of the '5'-cap'. Molecular selection of poly A(+) RNA for transport out of the nucleus or further cytoplasmic processing may account for the higher percentage of the '5-cap' and the greater translational activity of the cytoplasmic poly A(+) RNA. During these studies, it was also found that the m7 guanosine of the '5'-cap' was not removed during translation of the mRNA in the wheat germ system; this result suggests that the '5'-cap' may associate with allosteric binding sites of initiation factor(s)."}
{"id": "PMID:194142", "title": "Integration of genomes on infectious viruses.", "content": "The article contains a review relating to the integration of genomes of infectious viruses in Eukaryotic cells. Data are presented that were obtained in the study of tissue cultures chronically infected with viruses, in the study of pathologic and ecologic processes. Based on the evidence accumulated, some theoretical and applied aspects of the problem are discussed.", "contents": "Integration of genomes on infectious viruses. The article contains a review relating to the integration of genomes of infectious viruses in Eukaryotic cells. Data are presented that were obtained in the study of tissue cultures chronically infected with viruses, in the study of pathologic and ecologic processes. Based on the evidence accumulated, some theoretical and applied aspects of the problem are discussed."}
{"id": "PMID:194144", "title": "[The significance of dietary fat in arteriosclerosis. An outmoded theory? (author's transl)].", "content": "The high cholesterol content of an atheroma, the frequent occurrence of myocardial infarction with high serum cholesterol, the extensive arteriosclerotic changes in diseases with high serum cholesterol (nephrosis, myxedema) and the occurrence of cholesterol deposits in the aorta in some animals fed with cholesterol are the principal arguments for the lipid theory of arteriosclerosis. But since many observations contradict this theory and the composition of the atheroma is the same as for many granulation tissues which are interpreted as a healing process, it is postulated that atheroma tissue is also to be interpreted as part of a reparative process. Such a hypothesis could explain all the well-known arteriosclerotic changes. Longterm studies in man for testing the serum cholesterol-lowering action of the \"unsaturated\" vegetable oils include serious errors of method and permit no confirmed conclusions.", "contents": "[The significance of dietary fat in arteriosclerosis. An outmoded theory? (author's transl)]. The high cholesterol content of an atheroma, the frequent occurrence of myocardial infarction with high serum cholesterol, the extensive arteriosclerotic changes in diseases with high serum cholesterol (nephrosis, myxedema) and the occurrence of cholesterol deposits in the aorta in some animals fed with cholesterol are the principal arguments for the lipid theory of arteriosclerosis. But since many observations contradict this theory and the composition of the atheroma is the same as for many granulation tissues which are interpreted as a healing process, it is postulated that atheroma tissue is also to be interpreted as part of a reparative process. Such a hypothesis could explain all the well-known arteriosclerotic changes. Longterm studies in man for testing the serum cholesterol-lowering action of the \"unsaturated\" vegetable oils include serious errors of method and permit no confirmed conclusions."}
{"id": "PMID:194145", "title": "[Significance of diabetes mellitus in the activation of the varicella zoster virus (author's transl)].", "content": "Eruptive herpes zoster infection (VZV) and its primary and secondary diseases are reported in 28 patients aged between 25 and 85 years. In 2 cases, malignant primary diseases were found. In 16 patients, a disorder of glucose utilization was diagnosed, 8 of them accompanied by a disorder of fat metabolism and 5 by a hyperuricemia. In one case a severe encephalomyelitis was observed. In 2 patients the activation of the VZV infection was related to the cytostatic or immunosuppressive therapy of a generalized Hodgkin's disease and a multiple sclerosis. Once a liver abscess as a sequel to amebic dysentery was diagnosed and once a megaloplastic anemia with symptoms of a funicular myelopathy following a vitamin B12 deficiency syndrome. In VZV infection the search for basal metabolic disorders is of particular importance.", "contents": "[Significance of diabetes mellitus in the activation of the varicella zoster virus (author's transl)]. Eruptive herpes zoster infection (VZV) and its primary and secondary diseases are reported in 28 patients aged between 25 and 85 years. In 2 cases, malignant primary diseases were found. In 16 patients, a disorder of glucose utilization was diagnosed, 8 of them accompanied by a disorder of fat metabolism and 5 by a hyperuricemia. In one case a severe encephalomyelitis was observed. In 2 patients the activation of the VZV infection was related to the cytostatic or immunosuppressive therapy of a generalized Hodgkin's disease and a multiple sclerosis. Once a liver abscess as a sequel to amebic dysentery was diagnosed and once a megaloplastic anemia with symptoms of a funicular myelopathy following a vitamin B12 deficiency syndrome. In VZV infection the search for basal metabolic disorders is of particular importance."}
{"id": "PMID:194146", "title": "[Vaccinations of animals and human health (author's transl)].", "content": "Vaccination of animals may have both positive and negative effects on human health. The negative consequences largely occur with live vaccines. The protection provided by vaccination to animals is taken advantage of for human health in the most diverse ways, both directly and indirectly. Typical examples are vaccination of dogs and cats against against rabies and inoculation against diseases of cattle, horses and dogs in which reoviruses of serotypes 1, 2 and 3 are involved. An important contribution to the protection of human health is also provided by vaccination with inactivated pathogens against leptospirosis and salmonellosis, against stomatitis vesicularis and American equine encephalitis and in developing countries against brucellosis.", "contents": "[Vaccinations of animals and human health (author's transl)]. Vaccination of animals may have both positive and negative effects on human health. The negative consequences largely occur with live vaccines. The protection provided by vaccination to animals is taken advantage of for human health in the most diverse ways, both directly and indirectly. Typical examples are vaccination of dogs and cats against against rabies and inoculation against diseases of cattle, horses and dogs in which reoviruses of serotypes 1, 2 and 3 are involved. An important contribution to the protection of human health is also provided by vaccination with inactivated pathogens against leptospirosis and salmonellosis, against stomatitis vesicularis and American equine encephalitis and in developing countries against brucellosis."}
{"id": "PMID:194147", "title": "Alkaline sucrose sedimentation studies of MMS-induced DNA single-strand breakage and rejoining in the wild type and in UV-sensitive mutants of Saccharomyces cerevisiae.", "content": "MMS-induced DNA single-strand breakage and rejoining was studied in the RAD strain and in rad6 and rad21 mutants, both very sensitive to this treatment as compared with the wild type. Alkaline sucrose gradient centrifugation showed that MMS treatment reduced the molecular weight of DNA in the RAD strain and in rad6 and rad21 mutants to the same extent. Four hours of post-incubation in synthetic growth medium after treatment with a dose of 0.4% MMS which reduces cell survival of RAD, rad21 and rad6 to 50, 20 and less than 0.01%, respectively, resulted in a significant increase in the molecular weight of DNA in the wild type, but in only slight increase in mutant strains. When the strains were exposed to a lower dose of MMS (0.04%) which led to 100% survival of RAD and 50 and 20% survival of rad21 and rad6, respectively, wild-type DNA sedimented to the position of control DNA, while in both mutants the increase in molecular weight of DNA was less pronounced.", "contents": "Alkaline sucrose sedimentation studies of MMS-induced DNA single-strand breakage and rejoining in the wild type and in UV-sensitive mutants of Saccharomyces cerevisiae. MMS-induced DNA single-strand breakage and rejoining was studied in the RAD strain and in rad6 and rad21 mutants, both very sensitive to this treatment as compared with the wild type. Alkaline sucrose gradient centrifugation showed that MMS treatment reduced the molecular weight of DNA in the RAD strain and in rad6 and rad21 mutants to the same extent. Four hours of post-incubation in synthetic growth medium after treatment with a dose of 0.4% MMS which reduces cell survival of RAD, rad21 and rad6 to 50, 20 and less than 0.01%, respectively, resulted in a significant increase in the molecular weight of DNA in the wild type, but in only slight increase in mutant strains. When the strains were exposed to a lower dose of MMS (0.04%) which led to 100% survival of RAD and 50 and 20% survival of rad21 and rad6, respectively, wild-type DNA sedimented to the position of control DNA, while in both mutants the increase in molecular weight of DNA was less pronounced."}
{"id": "PMID:194148", "title": "Caffeine toxicity in drosophila strains having different MMS sensitivities.", "content": "Larvae of Drosophila melanogaster were fed with caffeine, and the induced lethality was recorded using two different methods. With a wild-type strain a whole dose-response curve was obtained. The two sexes were equally sensitive. Four genetically different strains, showing different MMS sensitivities, were tested with two caffeine doses. The strains differed significantly in their caffeine sensitivity, but there existed no correlation between MMS and caffeine sensitivity.", "contents": "Caffeine toxicity in drosophila strains having different MMS sensitivities. Larvae of Drosophila melanogaster were fed with caffeine, and the induced lethality was recorded using two different methods. With a wild-type strain a whole dose-response curve was obtained. The two sexes were equally sensitive. Four genetically different strains, showing different MMS sensitivities, were tested with two caffeine doses. The strains differed significantly in their caffeine sensitivity, but there existed no correlation between MMS and caffeine sensitivity."}
{"id": "PMID:194149", "title": "Asbestos and glass fibres in bacterial mutation tests.", "content": "Asbestos fibres are carcinogenic in man and experimental animals but fine glass fibres are known, at present, only to be carcinogenic in experimental animals. Asbestos and glass fibres have been studied in mutation tests using auxotrophic strains of Escherichia coli and Salmonella typhimurium. The mutagenic activities of the positive control mutagens ultraviolet light, potassium chromate, ethyl methanesulphonate and benzo(a)pyrene were detected in the experiments. However, no mutagenic activity was found to be associted with any of the asbestos and glass fibres tested over a wide range of concentrations. The implications of these findings for the mode of action of asbestos and glass fibres as carcinogens are discussed.", "contents": "Asbestos and glass fibres in bacterial mutation tests. Asbestos fibres are carcinogenic in man and experimental animals but fine glass fibres are known, at present, only to be carcinogenic in experimental animals. Asbestos and glass fibres have been studied in mutation tests using auxotrophic strains of Escherichia coli and Salmonella typhimurium. The mutagenic activities of the positive control mutagens ultraviolet light, potassium chromate, ethyl methanesulphonate and benzo(a)pyrene were detected in the experiments. However, no mutagenic activity was found to be associted with any of the asbestos and glass fibres tested over a wide range of concentrations. The implications of these findings for the mode of action of asbestos and glass fibres as carcinogens are discussed."}
{"id": "PMID:194151", "title": "Familial hemochromatosis. Physiologic studies in the precirrhotic stage of the disease.", "content": "We studied 12 members of a family with precirrhotic hemochromatosis to define the physiologic abnormalities in the asymptomatic phase of the disease. Six of 12 had increased iron stores; the mode of inheritance was consistent with an autosomal dominant trait. Serum ferritin levels were no more predictive of tissue iron levels than measurements of serum iron, transferrin saturation or chelatable iron excretion. In three affected family members intestinal iron content was normal. Liver proline hydroxylase activity and urinary hydroxyproline excretion did not correlate with tissue iron content, suggesting that, in addition to the possible role of tissue iron, hepatic fibrosis may involve other factors. \"Borderline diabetes mellitus\" was present in three affected family members, but extensive studies revealed that pituitary dysfunction is uncommon in early hemochromatosis. Increased levels of liver iron proved to be the most reliable marker for the disease.", "contents": "Familial hemochromatosis. Physiologic studies in the precirrhotic stage of the disease. We studied 12 members of a family with precirrhotic hemochromatosis to define the physiologic abnormalities in the asymptomatic phase of the disease. Six of 12 had increased iron stores; the mode of inheritance was consistent with an autosomal dominant trait. Serum ferritin levels were no more predictive of tissue iron levels than measurements of serum iron, transferrin saturation or chelatable iron excretion. In three affected family members intestinal iron content was normal. Liver proline hydroxylase activity and urinary hydroxyproline excretion did not correlate with tissue iron content, suggesting that, in addition to the possible role of tissue iron, hepatic fibrosis may involve other factors. \"Borderline diabetes mellitus\" was present in three affected family members, but extensive studies revealed that pituitary dysfunction is uncommon in early hemochromatosis. Increased levels of liver iron proved to be the most reliable marker for the disease."}
{"id": "PMID:194152", "title": "Plasma high-density lipoprotein concentrations in chronic-hemodialysis and renal-transplant patients.", "content": "Since epidemiologic studies show that the risk of clinically evident atherosclerosis correlates negatively with concentrations of high-density lipoprotein, we sought to determine whether patients on chronic hemodialysis or recipients of renal transplants had alterations in this lipoprotein similar to those described in other disorders associated with accelerated forms of atherosclerosis. High-density-lipoprotein cholesterol concentrations in both groups of renal patients were significantly lower than control values (P less than 0.01), and their ratios of low-density-lipoprotein to high-density-lipoprotein cholesterol were significantly higher (P less than 0.01) than those observed in both randomly selected controls and in controls matched for plasma lipid levels (control, 2.4 +/- 1.2, dialysis, 3.7 +/- 2.1, and transplant, 5.4 +/- 2.3 mg per 100 ml [mean +/- S.D.]) if, as experimental evidence suggests, high-density lipoprotein retards the development of atherosclerosis, and low-density lipoprotein has opposite effects, the higher ratio of low-density-lipoprotein to high-density-lipoprotein cholesterol found in chronic-dialysis and renal-transplant patients may be related to their premature morbidity and mortality from cardiovascular causes.", "contents": "Plasma high-density lipoprotein concentrations in chronic-hemodialysis and renal-transplant patients. Since epidemiologic studies show that the risk of clinically evident atherosclerosis correlates negatively with concentrations of high-density lipoprotein, we sought to determine whether patients on chronic hemodialysis or recipients of renal transplants had alterations in this lipoprotein similar to those described in other disorders associated with accelerated forms of atherosclerosis. High-density-lipoprotein cholesterol concentrations in both groups of renal patients were significantly lower than control values (P less than 0.01), and their ratios of low-density-lipoprotein to high-density-lipoprotein cholesterol were significantly higher (P less than 0.01) than those observed in both randomly selected controls and in controls matched for plasma lipid levels (control, 2.4 +/- 1.2, dialysis, 3.7 +/- 2.1, and transplant, 5.4 +/- 2.3 mg per 100 ml [mean +/- S.D.]) if, as experimental evidence suggests, high-density lipoprotein retards the development of atherosclerosis, and low-density lipoprotein has opposite effects, the higher ratio of low-density-lipoprotein to high-density-lipoprotein cholesterol found in chronic-dialysis and renal-transplant patients may be related to their premature morbidity and mortality from cardiovascular causes."}
{"id": "PMID:194153", "title": "Adherence of human peripheral blood lymphycytes to measles-infected cells. Enhancement by prostaglandin E1.", "content": "We studied the effect of prostaglandins in vitro on an immune reaction mediated by T cells; adherence of lymphocytes to measles-virus-infected human epithelial cells. Normal human lymphocytes adhered to a mean +/- S.D. 20.1 +/- 5.2 per cent of these HEp-2 cells. The percentage positive cells increased to 50.3 +/- 5.7 when lymphocytes were incubated with 10(-6) M prostaglandin E1 (P less than 0.01 vs. untreated lymphocytes); 10(-8) M and 10(-10) M were as effective. Prostaglandin F2alpha had no effect on lymphocyte adherence. Prostaglandin E1 increased lymphocyte cyclic AMP five to 10 times whereas prostagladin F2alpha did not affect cellular levels of this nucleotide. Dibutyryl cyclic AMP (10(-8) M) increased lymphocyte adherence: positive human epithelial cells increased from 16.0 +/- 2.4 to 38.7 +/- 1.1 per cent (P less than 0.01). Prostagladin E1 also increased adherence of lymphocytes from patients with systemic lupus erythematosus from 21.8 +/- 5.8 to 52.5 +/- 9.2 per cent (P less than 0.01). These results indicate that prostagladin E1 and cyclic AMP may serve to stimulate T-cell function and cell-mediated immunity.", "contents": "Adherence of human peripheral blood lymphycytes to measles-infected cells. Enhancement by prostaglandin E1. We studied the effect of prostaglandins in vitro on an immune reaction mediated by T cells; adherence of lymphocytes to measles-virus-infected human epithelial cells. Normal human lymphocytes adhered to a mean +/- S.D. 20.1 +/- 5.2 per cent of these HEp-2 cells. The percentage positive cells increased to 50.3 +/- 5.7 when lymphocytes were incubated with 10(-6) M prostaglandin E1 (P less than 0.01 vs. untreated lymphocytes); 10(-8) M and 10(-10) M were as effective. Prostaglandin F2alpha had no effect on lymphocyte adherence. Prostaglandin E1 increased lymphocyte cyclic AMP five to 10 times whereas prostagladin F2alpha did not affect cellular levels of this nucleotide. Dibutyryl cyclic AMP (10(-8) M) increased lymphocyte adherence: positive human epithelial cells increased from 16.0 +/- 2.4 to 38.7 +/- 1.1 per cent (P less than 0.01). Prostagladin E1 also increased adherence of lymphocytes from patients with systemic lupus erythematosus from 21.8 +/- 5.8 to 52.5 +/- 9.2 per cent (P less than 0.01). These results indicate that prostagladin E1 and cyclic AMP may serve to stimulate T-cell function and cell-mediated immunity."}
{"id": "PMID:194157", "title": "The natural history of recurrent herpes simplex labialis: implications for antiviral therapy.", "content": "We performed daily examination of 80 patients with recurrent herpes simplex labialis to define the course of the disease and to identify quantitative and objective measurements for use in monitoring the efficacy of antiviral chemotherapy. Pain, lesion size, mean virus titers from lesion swabs (10(5) plaque-forming units [PFU]) and frequency of virus-positive lesions (89 per cent) were maximal during the first 24 hours and decreased thereafter. Lesion punch-biopsy virus titers increased from a mean of less than 10(1) PFU in the prodromal and erythema stages to a mean of 10(4.7) in the vesicle stage. MEasurements potentially useful in monitoring antiviral efficacy include: time to loss of crust, time to complete healing, intensity and duration of lesion pain, area defined by lesion virus titer and duration of lesion virus excretion, and maximum lesion virus titer after the first visit. Early application of topical antiviral therapy should theoretically be able to alter the course of this disease.", "contents": "The natural history of recurrent herpes simplex labialis: implications for antiviral therapy. We performed daily examination of 80 patients with recurrent herpes simplex labialis to define the course of the disease and to identify quantitative and objective measurements for use in monitoring the efficacy of antiviral chemotherapy. Pain, lesion size, mean virus titers from lesion swabs (10(5) plaque-forming units [PFU]) and frequency of virus-positive lesions (89 per cent) were maximal during the first 24 hours and decreased thereafter. Lesion punch-biopsy virus titers increased from a mean of less than 10(1) PFU in the prodromal and erythema stages to a mean of 10(4.7) in the vesicle stage. MEasurements potentially useful in monitoring antiviral efficacy include: time to loss of crust, time to complete healing, intensity and duration of lesion pain, area defined by lesion virus titer and duration of lesion virus excretion, and maximum lesion virus titer after the first visit. Early application of topical antiviral therapy should theoretically be able to alter the course of this disease."}
{"id": "PMID:194158", "title": "Defective interfering particles with covalently linked [+/-]RNA induce interferon.", "content": "Defective interfering (DI) particles of vesicular stomatitis virus which contain covalently linked complementary [+]message and [-]anti-message RNA as a single-stranded ribonucleoprotein complex within the particle, are extremely efficient inducers of interferon. A single particle can induce a quantum yield of interferon. A single molecule of double-stranded RNA presumed to form, at least in part, on entry into the cell is thought to induce interferon synthesis. Conventional [-]RNA DI particles with the same polypeptide composition as [+/-]RNA DI particles fail to induce interferon.", "contents": "Defective interfering particles with covalently linked [+/-]RNA induce interferon. Defective interfering (DI) particles of vesicular stomatitis virus which contain covalently linked complementary [+]message and [-]anti-message RNA as a single-stranded ribonucleoprotein complex within the particle, are extremely efficient inducers of interferon. A single particle can induce a quantum yield of interferon. A single molecule of double-stranded RNA presumed to form, at least in part, on entry into the cell is thought to induce interferon synthesis. Conventional [-]RNA DI particles with the same polypeptide composition as [+/-]RNA DI particles fail to induce interferon."}
{"id": "PMID:194167", "title": "The cell-growth inhibitory effect of interferon. Studies of a resistant cell-subline.", "content": "Studies performed in the CSV subline of mouse L-cells suggest that activated endogenous and/or exogenous viral infection might be the factor that modifies the cell surface and, in consequence, the sensitivity of the cell to the cell-growth inhibitory action of interferon. In contrast with the parental L-cells, the CSV subline obtained by prolonged passage of L-cells in the presence of interferon shows an altered electron microscopic morphology, absence of C type particles and a decreased agglutinability with Concanavalin A. It is resistant to the cell-growth inhibitory effect of interferon but retains the sensitivity toward its antiviral effect. However, the sensitivity of the CSV subline toward the cell-growth inhibitory effect of interferon increased significantly after treatment with 5-iododexyuridine, infection with the Harvey strain of mouse sarcoma virus and/or prolonged passages in vitro. In this respect, the CSV subline resembles the primary mouse embryonic cells. Since sensitivity of CSV cells increased also after treatment with cyclic 3'-5' adenosine monophosphate and/or prostaglandin E2, it is possible that the cell-growth inhibitory effect of interferon is mediated through the \"second messenger\" system.", "contents": "The cell-growth inhibitory effect of interferon. Studies of a resistant cell-subline. Studies performed in the CSV subline of mouse L-cells suggest that activated endogenous and/or exogenous viral infection might be the factor that modifies the cell surface and, in consequence, the sensitivity of the cell to the cell-growth inhibitory action of interferon. In contrast with the parental L-cells, the CSV subline obtained by prolonged passage of L-cells in the presence of interferon shows an altered electron microscopic morphology, absence of C type particles and a decreased agglutinability with Concanavalin A. It is resistant to the cell-growth inhibitory effect of interferon but retains the sensitivity toward its antiviral effect. However, the sensitivity of the CSV subline toward the cell-growth inhibitory effect of interferon increased significantly after treatment with 5-iododexyuridine, infection with the Harvey strain of mouse sarcoma virus and/or prolonged passages in vitro. In this respect, the CSV subline resembles the primary mouse embryonic cells. Since sensitivity of CSV cells increased also after treatment with cyclic 3'-5' adenosine monophosphate and/or prostaglandin E2, it is possible that the cell-growth inhibitory effect of interferon is mediated through the \"second messenger\" system."}
{"id": "PMID:194168", "title": "Physical, chemical and serological properties of C-type virus associated with transplantable rat Thurzo-Svee leukemia.", "content": "Cells of rat Thurzo-Svee leukemia produce C-type virus. Viral particles are shown to contain high-molecular weight RNA and RNA-dependent DNA polymerase the virus possesses mammalian gs-3 antigen and rat species-specific gs-1 antigen and thus appears to be of rat origin.", "contents": "Physical, chemical and serological properties of C-type virus associated with transplantable rat Thurzo-Svee leukemia. Cells of rat Thurzo-Svee leukemia produce C-type virus. Viral particles are shown to contain high-molecular weight RNA and RNA-dependent DNA polymerase the virus possesses mammalian gs-3 antigen and rat species-specific gs-1 antigen and thus appears to be of rat origin."}
{"id": "PMID:194169", "title": "Skeletal changes and growth in experimental uremia.", "content": "Longitudinal growth; bone and growth zone histology; growth cartilage and bone mineralization (tetracycline technique); bone Ca content (neutron activation analysis); bone radiology; serum and urine chemistry; urinary cAMP and serum 25-OH-vitamin D3 were studied in a long-term model of experimental uremia in the rat. Uremia was induced by two-stage subtotal nephrectomy with irradiation of the remaining parenchyma. Ccr in the experimental group was 113 +/- 5.8 micron1/min X 100 g (19.8% of controls) and serum creatinine 1.67 +/- 0.04 mg% (5.1 X control value). Uremic animals were pair-fed with sham-operated controls. In the proximal tibia delayed transformation of cartilage into primary spongiosa with appearance of chondro-osteoid and delayed transformation of primary spongiosa into secondary spongiosa was observed (rickets). Increased amounts of osteoid were present although 25-OH-vitamin D3-levels were high. There were only modest signs of secondary hyperparathyroidism (osteoclast counts; urinary cAMP). In spite of the presence of bone disease, longitudinal growth was not reduced in uremic animals as compared with pair-fed sham-operated animals, but was significantly reduced as compared with ad lib fed control animals. In contrast, weight gain was significantly diminished in uremic animals as compared with pair-fed sham-operated control animals. It is concluded that diminished intake of food is the major determinant of growth retardation in preterminal experimental renal failure.", "contents": "Skeletal changes and growth in experimental uremia. Longitudinal growth; bone and growth zone histology; growth cartilage and bone mineralization (tetracycline technique); bone Ca content (neutron activation analysis); bone radiology; serum and urine chemistry; urinary cAMP and serum 25-OH-vitamin D3 were studied in a long-term model of experimental uremia in the rat. Uremia was induced by two-stage subtotal nephrectomy with irradiation of the remaining parenchyma. Ccr in the experimental group was 113 +/- 5.8 micron1/min X 100 g (19.8% of controls) and serum creatinine 1.67 +/- 0.04 mg% (5.1 X control value). Uremic animals were pair-fed with sham-operated controls. In the proximal tibia delayed transformation of cartilage into primary spongiosa with appearance of chondro-osteoid and delayed transformation of primary spongiosa into secondary spongiosa was observed (rickets). Increased amounts of osteoid were present although 25-OH-vitamin D3-levels were high. There were only modest signs of secondary hyperparathyroidism (osteoclast counts; urinary cAMP). In spite of the presence of bone disease, longitudinal growth was not reduced in uremic animals as compared with pair-fed sham-operated animals, but was significantly reduced as compared with ad lib fed control animals. In contrast, weight gain was significantly diminished in uremic animals as compared with pair-fed sham-operated control animals. It is concluded that diminished intake of food is the major determinant of growth retardation in preterminal experimental renal failure."}
{"id": "PMID:194171", "title": "Coxsackie A9 focal encephalitis associated with acute infantile hemiplegia and porencephaly.", "content": "The factors underlying acute infantile hemiplegia are seldom identified. Coxsackie A9 focal encephalitis was documented for the first time in a 3-month-old infant with fever, hemiconvulsions, and hemiplegia followed by a static motor deficit and epilepsy. It has been suggested that the acute infantile hemiplegia associated with encephalitis results from an arteritis or venous sinus thrombosis with subsequent cerebral infarction. However, this was not observed in our patient. Rather, a series of brain scans, computerized tomograms, and a cerebral angiogram clearly documented the evolution of a focal necrotizing encephaloclastic process resulting in a porencephalic cyst. Serial cerebrospinal fluid viral cultures were necessary to isolate the etiologic agent (tcoxsackie A9). The infant did not have a neutralizing antibody response to the infecting viral agent despite an apparently intact immune system, which possibly may be explained by the developed of immune tolerance or an insufficient amount of infecting viral antigen. This emphasizes that serologic studies alone may not be adequate to document an acute central nervous system viral infection. This patient also typifies the poor prognosis in infants presenting with acute hemiplegia, fever, and convulsions in the absence of cerebrovascular occlusion.", "contents": "Coxsackie A9 focal encephalitis associated with acute infantile hemiplegia and porencephaly. The factors underlying acute infantile hemiplegia are seldom identified. Coxsackie A9 focal encephalitis was documented for the first time in a 3-month-old infant with fever, hemiconvulsions, and hemiplegia followed by a static motor deficit and epilepsy. It has been suggested that the acute infantile hemiplegia associated with encephalitis results from an arteritis or venous sinus thrombosis with subsequent cerebral infarction. However, this was not observed in our patient. Rather, a series of brain scans, computerized tomograms, and a cerebral angiogram clearly documented the evolution of a focal necrotizing encephaloclastic process resulting in a porencephalic cyst. Serial cerebrospinal fluid viral cultures were necessary to isolate the etiologic agent (tcoxsackie A9). The infant did not have a neutralizing antibody response to the infecting viral agent despite an apparently intact immune system, which possibly may be explained by the developed of immune tolerance or an insufficient amount of infecting viral antigen. This emphasizes that serologic studies alone may not be adequate to document an acute central nervous system viral infection. This patient also typifies the poor prognosis in infants presenting with acute hemiplegia, fever, and convulsions in the absence of cerebrovascular occlusion."}
{"id": "PMID:194173", "title": "[A case of recurrent hemoperitoneum caused by hepatocarcinoma].", "content": "A case of recurring haemoperitoneum caused by liver cancer is presented. This neoplasia, rare itself in Italy, may have a variety of clinical pictures. Recurring haemoperitoneum is quite exceptional and mistaken diagnosis and aetiopathogenetic interpretation are the likely results. The symptomatology is illustrated and the problem of diagnosis is discussed.", "contents": "[A case of recurrent hemoperitoneum caused by hepatocarcinoma]. A case of recurring haemoperitoneum caused by liver cancer is presented. This neoplasia, rare itself in Italy, may have a variety of clinical pictures. Recurring haemoperitoneum is quite exceptional and mistaken diagnosis and aetiopathogenetic interpretation are the likely results. The symptomatology is illustrated and the problem of diagnosis is discussed."}
{"id": "PMID:194175", "title": "[Contribution of laparoscopy-biopsy to the diagnosis of primary liver neoplasms].", "content": "After a review of the literature, personal observations of primary benign and malignant tumours of the liver, studied using laparoscopic biopsy are presented and the importance of this examination in the early diagnosis of primary hepatic tumours is stressed. This examination, particularly when associated with biopsy, is very useful since it reduces diagnosis time with little or no risk to the patient with a high percentage of positive results.", "contents": "[Contribution of laparoscopy-biopsy to the diagnosis of primary liver neoplasms]. After a review of the literature, personal observations of primary benign and malignant tumours of the liver, studied using laparoscopic biopsy are presented and the importance of this examination in the early diagnosis of primary hepatic tumours is stressed. This examination, particularly when associated with biopsy, is very useful since it reduces diagnosis time with little or no risk to the patient with a high percentage of positive results."}
{"id": "PMID:194178", "title": "Endometrial cancer associated with feminizing ovarian tumor and polycystic ovarian disease.", "content": "Feminizing ovarian tumors and polycystic ovarian disease may cause endometrial cancer by abnormal, unopposed endogenous estrogenic stimulation. We reviewed the clinical course of 72 endometrial cancer patients with a concomitant feminizing ovarian tumor or polycystic ovarian disease and compared tumor characteristics and treatment results with those exhibited by 523 patients treated for endometrial cancer alone. With functioning ovarian tumor and with polycystic ovaries, the cancer tended to be more often low-grade, low-stage, and superficial than did endometrial cancer alone. The high 5-year and 10-year survival rates observed in our functioning ovarian tumor-polycystic ovary patients support the conclusion that endometrial carcinoma with a coexistent endogenous estrogenic stimulus has a more favorable prognosis (P less than 0.01) than endometrial carcinoma alone.", "contents": "Endometrial cancer associated with feminizing ovarian tumor and polycystic ovarian disease. Feminizing ovarian tumors and polycystic ovarian disease may cause endometrial cancer by abnormal, unopposed endogenous estrogenic stimulation. We reviewed the clinical course of 72 endometrial cancer patients with a concomitant feminizing ovarian tumor or polycystic ovarian disease and compared tumor characteristics and treatment results with those exhibited by 523 patients treated for endometrial cancer alone. With functioning ovarian tumor and with polycystic ovaries, the cancer tended to be more often low-grade, low-stage, and superficial than did endometrial cancer alone. The high 5-year and 10-year survival rates observed in our functioning ovarian tumor-polycystic ovary patients support the conclusion that endometrial carcinoma with a coexistent endogenous estrogenic stimulus has a more favorable prognosis (P less than 0.01) than endometrial carcinoma alone."}
{"id": "PMID:194194", "title": "Inhibition of glycolytic enzymes of rat liver and hepatomas by free fatty acids.", "content": "The action of free fatty acids on glycolytic enzymes was compared in normal and neoplastic tissues. Preincubation of tissue supernatant fractions with octanoate or laurate caused an inhibition of the activities of hexokinase and phosphofructokinase. An inhibition was also observed of lactate production with either glucose or glucose 6-phosphate as substrate. A similar degree of inhibition was observed for actions on normal liver and kidney, on the 7800 and 3924-A hepatomas and on the MK-3 renal cortical tumor. The possible relationship between the inhibition of glycolytic enzymes by fatty acids and anti-tumor activity previously observed with these compounds was noted.", "contents": "Inhibition of glycolytic enzymes of rat liver and hepatomas by free fatty acids. The action of free fatty acids on glycolytic enzymes was compared in normal and neoplastic tissues. Preincubation of tissue supernatant fractions with octanoate or laurate caused an inhibition of the activities of hexokinase and phosphofructokinase. An inhibition was also observed of lactate production with either glucose or glucose 6-phosphate as substrate. A similar degree of inhibition was observed for actions on normal liver and kidney, on the 7800 and 3924-A hepatomas and on the MK-3 renal cortical tumor. The possible relationship between the inhibition of glycolytic enzymes by fatty acids and anti-tumor activity previously observed with these compounds was noted."}
{"id": "PMID:194195", "title": "The effect of crocetin on skin papillomas and Rous sarcoma.", "content": "A carotenoid compound, crocetin, was used in two different types of tests involving animal tumors. These tests showed that crocetin both decreased the numbers of tumors as well as delaying onset.", "contents": "The effect of crocetin on skin papillomas and Rous sarcoma. A carotenoid compound, crocetin, was used in two different types of tests involving animal tumors. These tests showed that crocetin both decreased the numbers of tumors as well as delaying onset."}
{"id": "PMID:194196", "title": "Scanning electron microscopic studies of herpes simplex virus transformed cells.", "content": "The surface morphology of herpes simplex virus transformed cells was examined by scanning electron microscopy in exponentially growing and density inhibited rat embryo fibroblast cultures. The cell surface of oncogenically-transformed cells became more villated and many microvilli showed branching. C-type virus particles budding from the cell surface were commonly observed. Virus induced cytopathic effects observed by scanning electron microscopy, included rounding up and detachment of degenerating cells from the substrate.", "contents": "Scanning electron microscopic studies of herpes simplex virus transformed cells. The surface morphology of herpes simplex virus transformed cells was examined by scanning electron microscopy in exponentially growing and density inhibited rat embryo fibroblast cultures. The cell surface of oncogenically-transformed cells became more villated and many microvilli showed branching. C-type virus particles budding from the cell surface were commonly observed. Virus induced cytopathic effects observed by scanning electron microscopy, included rounding up and detachment of degenerating cells from the substrate."}
{"id": "PMID:194197", "title": "A status report: human prostatic carcinoma, with emphasis on potential for viral etiology.", "content": "Several parameters of the biology of cancer of the prostate have been reviewed with a continuing assessment of the possible etiologic role of virus. These aspects include epidemiology, clinical studies, morphology, pathology, enzymology, immunology, endocrinology, model animal studies, in vitro systems, and viral investigations. From available literature it is concluded that, to date, the association with several urogenital tissues of herpes-type viruses has been best documented. It is suggested that a fundamental barrier to more sophisticated virologic and biologic studies is the lack of long term cell cultures of normal and pathologic prostate epithelium from males of all ages.", "contents": "A status report: human prostatic carcinoma, with emphasis on potential for viral etiology. Several parameters of the biology of cancer of the prostate have been reviewed with a continuing assessment of the possible etiologic role of virus. These aspects include epidemiology, clinical studies, morphology, pathology, enzymology, immunology, endocrinology, model animal studies, in vitro systems, and viral investigations. From available literature it is concluded that, to date, the association with several urogenital tissues of herpes-type viruses has been best documented. It is suggested that a fundamental barrier to more sophisticated virologic and biologic studies is the lack of long term cell cultures of normal and pathologic prostate epithelium from males of all ages."}
{"id": "PMID:194198", "title": "[Somatic hybridization and oncogenesis: induction of tumors in mice by administration of mixtures of cells of the homologous organs and their hybrids].", "content": "The 2 months old C57BL/6J mice were injected with the mixtures of kidney and spleen cells from mice of the same strain or of the same cells following the hybridization induced by Sendai virus. The tumours of liver, kidney and lymphoid system appeared in 25% of recipients within 12--14 months. The result obtained is predicted by the general theory of oncogenesis proposed early by L. B. Mekler.", "contents": "[Somatic hybridization and oncogenesis: induction of tumors in mice by administration of mixtures of cells of the homologous organs and their hybrids]. The 2 months old C57BL/6J mice were injected with the mixtures of kidney and spleen cells from mice of the same strain or of the same cells following the hybridization induced by Sendai virus. The tumours of liver, kidney and lymphoid system appeared in 25% of recipients within 12--14 months. The result obtained is predicted by the general theory of oncogenesis proposed early by L. B. Mekler."}
{"id": "PMID:194199", "title": "Blindness following blowout orbital fractures.", "content": "Blindness following blowout fractures is an unfortunate complication. The ophthalmologist must be aware of the events and sites of injury to the optic nerve which lead to visual problems. Preventive measures include immediate recognition of the signs of impending optic nerve compression and execution of treatment without delay. The importance of monitoring vision cannot be overstressed. Judicious surgery involves a post-injury delay in cases that are improving daily. The avoidance of additional surgical trauma with implant insertion during that period may help prevent postoperative blowout blindness.", "contents": "Blindness following blowout orbital fractures. Blindness following blowout fractures is an unfortunate complication. The ophthalmologist must be aware of the events and sites of injury to the optic nerve which lead to visual problems. Preventive measures include immediate recognition of the signs of impending optic nerve compression and execution of treatment without delay. The importance of monitoring vision cannot be overstressed. Judicious surgery involves a post-injury delay in cases that are improving daily. The avoidance of additional surgical trauma with implant insertion during that period may help prevent postoperative blowout blindness."}
{"id": "PMID:194200", "title": "Incidence of recurrent herpes labialis and upper respiratory infection: a prospective study of the influence of biologic, social and psychologic predictors.", "content": "In a 3-year prospective study of recurrent herpes labialis (RHL) in a population of 149 student nurses, 40 to 50 per cent of the variance in incidence could be explained by a small group of variables. Measures of previous experience with RHL accounted for the largest fraction of the explained variance, followed by upper respiratory infection (URI) rate, socioeconomic status, and mood trait, in order of declining influence. Timing of RHL episodes was not related to phase of the menstrual cycle.", "contents": "Incidence of recurrent herpes labialis and upper respiratory infection: a prospective study of the influence of biologic, social and psychologic predictors. In a 3-year prospective study of recurrent herpes labialis (RHL) in a population of 149 student nurses, 40 to 50 per cent of the variance in incidence could be explained by a small group of variables. Measures of previous experience with RHL accounted for the largest fraction of the explained variance, followed by upper respiratory infection (URI) rate, socioeconomic status, and mood trait, in order of declining influence. Timing of RHL episodes was not related to phase of the menstrual cycle."}
{"id": "PMID:194204", "title": "The role of cutaneous mechanoreceptors in thermal sensation and pain.", "content": "The functional behavior of slowly adapting cutaneous mechanoreceptors under combined thermal-mechanical stimulation was investigated by single-unit recordings from the lumbar dorsal roots of the cat. Increased sensitivity to bimodal stimulation was observed in 24 of the 28 units studied, employing stimulus-response functional behavior as the basis for judgment. Low-threshold receptors generally did not exhibit increased spontaneous firing as accompaniment to heightened sensitivity, while such enhanced basal activity was usually observed in moderate-threshold units in addition to increased reactivity. Information theory calculations performed on these stimulus-response data revealed that 15 of the 24 \"heat-sensitive\" receptors were additionally characterized by an enhanced ability to transmit neural information under bimodal  stimulation. These results were interpreted as supporting pattern theories of pain as opposed to the concept of receptor specificity. No contradiction was observed, however, between the present results and those of other investigators. The present conclusions derive from new criteria for thermal reactivity based upon innovative stimulus conditions.", "contents": "The role of cutaneous mechanoreceptors in thermal sensation and pain. The functional behavior of slowly adapting cutaneous mechanoreceptors under combined thermal-mechanical stimulation was investigated by single-unit recordings from the lumbar dorsal roots of the cat. Increased sensitivity to bimodal stimulation was observed in 24 of the 28 units studied, employing stimulus-response functional behavior as the basis for judgment. Low-threshold receptors generally did not exhibit increased spontaneous firing as accompaniment to heightened sensitivity, while such enhanced basal activity was usually observed in moderate-threshold units in addition to increased reactivity. Information theory calculations performed on these stimulus-response data revealed that 15 of the 24 \"heat-sensitive\" receptors were additionally characterized by an enhanced ability to transmit neural information under bimodal  stimulation. These results were interpreted as supporting pattern theories of pain as opposed to the concept of receptor specificity. No contradiction was observed, however, between the present results and those of other investigators. The present conclusions derive from new criteria for thermal reactivity based upon innovative stimulus conditions."}
{"id": "PMID:194206", "title": "Long-term alloxan diabetes in the rat. Study of mesangial cell morphology by serial biopsies.", "content": "Experimental diabetes in the rat was induced by alloxan (40 mg/kg body weight) and resulted in permanent hyperglycaemia (mean glycaemia: 403.0 mg/100 ml). The animals were left untreated for more than 16 months. The mesangial cell of the renal glomerulus was studied by serial biopsies performed each month under light anaesthesia in the diabetic animals and in normal controls of the same age. Large dense bodies appeared in the cytoplasm after 3 months in the diabetics and after 10 months in the controls. With time, a larger number of mesangial cells contained these dense bodies. At the end stage they seem to be mainly lipidic. When NO3Ag is given in the drinking water the dense bodies accumulate particles of silver, suggesting that they contain fragments of the basement membrane. While the acid phosphatase reaction was negative in biopsy specimens from diabetic animals, it remains possible that the large dense bodies belong to the lysosomial system. This point, as well as the pathologic significance of the dense bodies is currently investigated.", "contents": "Long-term alloxan diabetes in the rat. Study of mesangial cell morphology by serial biopsies. Experimental diabetes in the rat was induced by alloxan (40 mg/kg body weight) and resulted in permanent hyperglycaemia (mean glycaemia: 403.0 mg/100 ml). The animals were left untreated for more than 16 months. The mesangial cell of the renal glomerulus was studied by serial biopsies performed each month under light anaesthesia in the diabetic animals and in normal controls of the same age. Large dense bodies appeared in the cytoplasm after 3 months in the diabetics and after 10 months in the controls. With time, a larger number of mesangial cells contained these dense bodies. At the end stage they seem to be mainly lipidic. When NO3Ag is given in the drinking water the dense bodies accumulate particles of silver, suggesting that they contain fragments of the basement membrane. While the acid phosphatase reaction was negative in biopsy specimens from diabetic animals, it remains possible that the large dense bodies belong to the lysosomial system. This point, as well as the pathologic significance of the dense bodies is currently investigated."}
{"id": "PMID:194207", "title": "Tissue culture, electron microscopic and enzyme histochemical investigations of extraadrenal paragangliomas.", "content": "Light and electromicroscopical as well as histochemical investigations were performed on three cases of extraadrenal paragangliomas. They were localized in the carotid body, tympanicum and cauda equina region. Tissue of two cases was cultivated in vitro in nutrient medium TCM 199. The tumours were classified as paragangliomas of the paraganglionic type with typical cell clusters, of the adenomatous and angiomatous type. The enzyme histochemistry showed a very high dehydrogenase activity. Ultrastructurally numerous typical osmiophilic granules could be observed in the cytoplasm of the tumour cells. In tissue culture only a minimal cellular proliferative activity could be detected. The few proliferating cell colonies showed mostly characteristics of epithelial tissue and sometimes a similar behaviour to cells of a ganglioneuroblastoma. The minimal proliferative activity in vitro is in good agreement with the proliferative behaviour of the extraadrenal paragangliomas in vivo.", "contents": "Tissue culture, electron microscopic and enzyme histochemical investigations of extraadrenal paragangliomas. Light and electromicroscopical as well as histochemical investigations were performed on three cases of extraadrenal paragangliomas. They were localized in the carotid body, tympanicum and cauda equina region. Tissue of two cases was cultivated in vitro in nutrient medium TCM 199. The tumours were classified as paragangliomas of the paraganglionic type with typical cell clusters, of the adenomatous and angiomatous type. The enzyme histochemistry showed a very high dehydrogenase activity. Ultrastructurally numerous typical osmiophilic granules could be observed in the cytoplasm of the tumour cells. In tissue culture only a minimal cellular proliferative activity could be detected. The few proliferating cell colonies showed mostly characteristics of epithelial tissue and sometimes a similar behaviour to cells of a ganglioneuroblastoma. The minimal proliferative activity in vitro is in good agreement with the proliferative behaviour of the extraadrenal paragangliomas in vivo."}
{"id": "PMID:194208", "title": "The alveolar lining film in experimental pulmonary collapse.", "content": "Obstructive pulmonary collapse was produced by ligation of lobar bronchus in 41 healthy dogs. The atelectatic lung was examined electronmicroscopically by means of vapour fixation, ruthenium red procedure and tricomplex flocculation. The equilibration stability index of Pattle was determined and compared to the electromicroscopic findings. The experimentally produced obstructive pulmonary collapse was a mechanical phenomenon which secondarily caused qualitative changes in the production of the alveolar lining layer.", "contents": "The alveolar lining film in experimental pulmonary collapse. Obstructive pulmonary collapse was produced by ligation of lobar bronchus in 41 healthy dogs. The atelectatic lung was examined electronmicroscopically by means of vapour fixation, ruthenium red procedure and tricomplex flocculation. The equilibration stability index of Pattle was determined and compared to the electromicroscopic findings. The experimentally produced obstructive pulmonary collapse was a mechanical phenomenon which secondarily caused qualitative changes in the production of the alveolar lining layer."}
{"id": "PMID:194205", "title": "[Ultrastructure of the excretory system of the tick Ornithodoros papillipes (Argasidae)].", "content": "The ultafine structure of the Malpighian tubes in O. papillipes (Argasidae) was studied. It has been shown that the cells of different parts of the Malpighian tubes have their own peculiarities. The distal cells are characterized by the inclusions which can be interpreted as mucopolysaccharide ones. The main part of the tube was found to contain cells of two types. Most of the cells belonging to the first type have well developed microvilli and poorly developed basal invaginations. The cells of the second type, the number of which increases towards the proximal end of the tube, have small microvilli and narrow folds of the basal labyrinth entering deeply the cytoplasm. The cells of the second type are rich in mitochondria. The ultrastructure of the rectal sac has been studied. The cells of this organ have a polar structure: the apical surface is covered with microvilli, the plasmotic membrane forms deep folds at the base.", "contents": "[Ultrastructure of the excretory system of the tick Ornithodoros papillipes (Argasidae)]. The ultafine structure of the Malpighian tubes in O. papillipes (Argasidae) was studied. It has been shown that the cells of different parts of the Malpighian tubes have their own peculiarities. The distal cells are characterized by the inclusions which can be interpreted as mucopolysaccharide ones. The main part of the tube was found to contain cells of two types. Most of the cells belonging to the first type have well developed microvilli and poorly developed basal invaginations. The cells of the second type, the number of which increases towards the proximal end of the tube, have small microvilli and narrow folds of the basal labyrinth entering deeply the cytoplasm. The cells of the second type are rich in mitochondria. The ultrastructure of the rectal sac has been studied. The cells of this organ have a polar structure: the apical surface is covered with microvilli, the plasmotic membrane forms deep folds at the base."}
{"id": "PMID:194211", "title": "Rapid eye movement sleep, motoneurone inhibition, and apneic spells in preterm infants.", "content": "Not principally different from the results obtained in more mature subjects, monosynaptic reflex excitability of spinal motoneurones in preterm infants decreases during active sleep. However, in preterm infants the electric reflex response is not abolished, and is not even continuously depressed during the entire active sleep period. Spinal motoneurone inhibition is demonstrable only during certain periods of active sleep, and it is during this state of decreased spinal motoneurone excitability when apneic spells predominantly occur.", "contents": "Rapid eye movement sleep, motoneurone inhibition, and apneic spells in preterm infants. Not principally different from the results obtained in more mature subjects, monosynaptic reflex excitability of spinal motoneurones in preterm infants decreases during active sleep. However, in preterm infants the electric reflex response is not abolished, and is not even continuously depressed during the entire active sleep period. Spinal motoneurone inhibition is demonstrable only during certain periods of active sleep, and it is during this state of decreased spinal motoneurone excitability when apneic spells predominantly occur."}
{"id": "PMID:194212", "title": "Separation and characterization of cord serum lipoproteins.", "content": "Blood was collected from the umbilical cord of infants with a 1-min Apgar score of 9 to 10. Total cord serum lipoproteins were isolated by ultracentrifugation, at a density of 1.220 g/ml. The isolated serum lopoproteins were then separated by gel filtration chromatography on 6% agarose. The overall recovery of the separated lipoprotein cholesterol was 90% or greater. In cord serum, four lipoprotein peaks were found, whereas three peaks were present in adult lipoproteins. The major lipoproteins of cord serum correspond to low density lipoprotein (LDL) and high density lipoprotein (HDL). Very low density lipoproteins (VLDL) were heterogeneous in cord serum. After gel filtration chromatography, the distribution of cord serum cholesterol is about 5% in peak 1, 10% in peak 2, 40% in peak 3 (LDL), and 45% in peak 4 (HDL). An additional difference between the lipoproteins isolated from cord serum and those from adult serum was the slower electrophoretic mobility of cord serum VLDL in agarose gel.", "contents": "Separation and characterization of cord serum lipoproteins. Blood was collected from the umbilical cord of infants with a 1-min Apgar score of 9 to 10. Total cord serum lipoproteins were isolated by ultracentrifugation, at a density of 1.220 g/ml. The isolated serum lopoproteins were then separated by gel filtration chromatography on 6% agarose. The overall recovery of the separated lipoprotein cholesterol was 90% or greater. In cord serum, four lipoprotein peaks were found, whereas three peaks were present in adult lipoproteins. The major lipoproteins of cord serum correspond to low density lipoprotein (LDL) and high density lipoprotein (HDL). Very low density lipoproteins (VLDL) were heterogeneous in cord serum. After gel filtration chromatography, the distribution of cord serum cholesterol is about 5% in peak 1, 10% in peak 2, 40% in peak 3 (LDL), and 45% in peak 4 (HDL). An additional difference between the lipoproteins isolated from cord serum and those from adult serum was the slower electrophoretic mobility of cord serum VLDL in agarose gel."}
{"id": "PMID:194213", "title": "Lung phosphatidylcholine synthesis and cholinephosphotransferase activity in anencephalic rat fetuses with corticosteroid deficiency.", "content": "Adrenocortical insufficiency was produced in rat fetuses by surgical decapitation. These animals show low plasma corticosterone levels compared to littermate controls. Lung slices from anencephalic fetuses were found to have reduced incorporation of [14C]choline into phosphatidylcholine, hence diminished choline pathway activity; this abnoramlity was present at 21 days of gestation but not at term. Cholinephosphotransferase (CPT), the terminal catalyst of the choline pathway, also showed diminished activity in lungs of anencephalic fetuses, with a mean of 120 pmol/min/mg protein compared to a control value of 190. Dexamethasone treatment of these animals for 6-12 hr led to enhanced choline incorporation rates. Corticosteroid administration also restored CPT activity and even elevated the enzyme to a mean level (340 pmol/min/mg protein) greater than that found in normal fetuses at 21-22 days of gestation. The early pulmonary biochemical effects of dexamethasone in this model were not accompanied by recognizable ultrastructural changes.", "contents": "Lung phosphatidylcholine synthesis and cholinephosphotransferase activity in anencephalic rat fetuses with corticosteroid deficiency. Adrenocortical insufficiency was produced in rat fetuses by surgical decapitation. These animals show low plasma corticosterone levels compared to littermate controls. Lung slices from anencephalic fetuses were found to have reduced incorporation of [14C]choline into phosphatidylcholine, hence diminished choline pathway activity; this abnoramlity was present at 21 days of gestation but not at term. Cholinephosphotransferase (CPT), the terminal catalyst of the choline pathway, also showed diminished activity in lungs of anencephalic fetuses, with a mean of 120 pmol/min/mg protein compared to a control value of 190. Dexamethasone treatment of these animals for 6-12 hr led to enhanced choline incorporation rates. Corticosteroid administration also restored CPT activity and even elevated the enzyme to a mean level (340 pmol/min/mg protein) greater than that found in normal fetuses at 21-22 days of gestation. The early pulmonary biochemical effects of dexamethasone in this model were not accompanied by recognizable ultrastructural changes."}
{"id": "PMID:194214", "title": "Prolonged sleep apnea and respiratory instability: a discriminative study.", "content": "This report is based on a study of 53 infants, 28 of whom had clinically observed prolonged apnea (greater than or equal to 20 seconds) during sleep whereas the remaining did not. In addition to the clinical observations, each infant was studied in a sleep laboratory during a complete nap, and a continuous recording was made of respiratory activity and rapid eye movements. Measurements were made of all apneic pauses (greater than or equal to 2 seconds) observed in the laboratory and the two groups of infants were compared in terms of the frequency and average duration of apneic pauses, the longest apneic pause, the amount of periodic apnea, and the relative amount of apnea. The infants with prolonged sleep apnea had, during a single nap, more frequent and longer apneic pauses and more periodic apnea. This supports the hypothesis that respiratory instability during sleep and prolonged apnea have a common etiology. By employing a multiple linear regression model and including all laboratory apnea measures in a single analysis, a composite laboratory score was developed to differentiate members of the two groups. It would thus appear that the study of infants during a single nap could assist in the identification of infants at risk for prolonged sleep apnea and provide an indirect method for determining the influence of a number of variables on the occurrence of prolonged sleep apnea. Pediatrics, 59:962-970, 1977, SLEEP, APNEA, RESPIRATORY INSTABILITY.", "contents": "Prolonged sleep apnea and respiratory instability: a discriminative study. This report is based on a study of 53 infants, 28 of whom had clinically observed prolonged apnea (greater than or equal to 20 seconds) during sleep whereas the remaining did not. In addition to the clinical observations, each infant was studied in a sleep laboratory during a complete nap, and a continuous recording was made of respiratory activity and rapid eye movements. Measurements were made of all apneic pauses (greater than or equal to 2 seconds) observed in the laboratory and the two groups of infants were compared in terms of the frequency and average duration of apneic pauses, the longest apneic pause, the amount of periodic apnea, and the relative amount of apnea. The infants with prolonged sleep apnea had, during a single nap, more frequent and longer apneic pauses and more periodic apnea. This supports the hypothesis that respiratory instability during sleep and prolonged apnea have a common etiology. By employing a multiple linear regression model and including all laboratory apnea measures in a single analysis, a composite laboratory score was developed to differentiate members of the two groups. It would thus appear that the study of infants during a single nap could assist in the identification of infants at risk for prolonged sleep apnea and provide an indirect method for determining the influence of a number of variables on the occurrence of prolonged sleep apnea. Pediatrics, 59:962-970, 1977, SLEEP, APNEA, RESPIRATORY INSTABILITY."}
{"id": "PMID:194215", "title": "A comparative study of the calcium accumulation by mitochondria and microsomes isolated from the smooth muscle of the guinea-pig taenia coli.", "content": "The calcium uptake by mitochondria and microsomes isolated from the guinea-pig taenia coli was studied at physiological Ca2+ concentrations, buffered by Ca-EGTA mixtures. The Ca accumulation by the mitochondria was measured from the difference between the amount of Ca taken up in the presence and in the absence of a specific mitochondrial inhibitor. The Ca uptake by the microsomes was determined in a solution containing oxalate and a mitochondrial inhibitor. It was calculated from the difference in Ca uptake measured with and without ATP. By using this procedure, the necessity of extensive purification of the isolated fractions was avoided. The (Ca2+) for half-maximal transport in the mitochondria is 7 X 10(-6) M. At (Ca2+) lower than 2 X 10(-7) M, Ca is taken up in an energy-dependent way. In the microsomes the apparent Km for Ca is 7 X 10(-7) m. accumulation is still stimulated by ATP at a (Ca2+) as low as 4 X 10(-8) M. The results show that the rate of Ca uptake by the cell organelles corresponding to the microsomal vesicles is sufficiently fast to explain the speed of relaxation of the taenia coli. The results also suggest that these cell organelles are more important than the mitochondria in regulating the cytoplasmic Ca concentration.", "contents": "A comparative study of the calcium accumulation by mitochondria and microsomes isolated from the smooth muscle of the guinea-pig taenia coli. The calcium uptake by mitochondria and microsomes isolated from the guinea-pig taenia coli was studied at physiological Ca2+ concentrations, buffered by Ca-EGTA mixtures. The Ca accumulation by the mitochondria was measured from the difference between the amount of Ca taken up in the presence and in the absence of a specific mitochondrial inhibitor. The Ca uptake by the microsomes was determined in a solution containing oxalate and a mitochondrial inhibitor. It was calculated from the difference in Ca uptake measured with and without ATP. By using this procedure, the necessity of extensive purification of the isolated fractions was avoided. The (Ca2+) for half-maximal transport in the mitochondria is 7 X 10(-6) M. At (Ca2+) lower than 2 X 10(-7) M, Ca is taken up in an energy-dependent way. In the microsomes the apparent Km for Ca is 7 X 10(-7) m. accumulation is still stimulated by ATP at a (Ca2+) as low as 4 X 10(-8) M. The results show that the rate of Ca uptake by the cell organelles corresponding to the microsomal vesicles is sufficiently fast to explain the speed of relaxation of the taenia coli. The results also suggest that these cell organelles are more important than the mitochondria in regulating the cytoplasmic Ca concentration."}
{"id": "PMID:194216", "title": "Pharmacological evidence in vitro and in vivo for functional beta1 receptors in the cerebral circulation.", "content": "Blood flow in the caudate nucleus was measured by the thermoclearance technique in non-anesthetized rabbits, accompanied by recording of electrocorticogram, systemic blood pressure, and Pao2 and Paco2 (mass spectrometry). Isoprenaline increased caudate nucleus blood flow and reduced systemic blood pressure. The beta2-receptor agonist, terbutaline, on the other hand, had only peripheral effects. The caudate nucleus flow response was selectively blocked by the beta1-receptor antagonist, practolol, whereas propranolol inhibited all effects of both agonists. Isoprenaline dilated isolated pieces of the tributary artery (middle cerebral) tested in cats, the effect being inhibited not only by propranolol but also by practolol. The results offer further evidence for the view that the beta-receptors in the cerebral vascular bed are of the beta1-type.", "contents": "Pharmacological evidence in vitro and in vivo for functional beta1 receptors in the cerebral circulation. Blood flow in the caudate nucleus was measured by the thermoclearance technique in non-anesthetized rabbits, accompanied by recording of electrocorticogram, systemic blood pressure, and Pao2 and Paco2 (mass spectrometry). Isoprenaline increased caudate nucleus blood flow and reduced systemic blood pressure. The beta2-receptor agonist, terbutaline, on the other hand, had only peripheral effects. The caudate nucleus flow response was selectively blocked by the beta1-receptor antagonist, practolol, whereas propranolol inhibited all effects of both agonists. Isoprenaline dilated isolated pieces of the tributary artery (middle cerebral) tested in cats, the effect being inhibited not only by propranolol but also by practolol. The results offer further evidence for the view that the beta-receptors in the cerebral vascular bed are of the beta1-type."}
{"id": "PMID:194219", "title": "[Scanning of the myocardium with pyrophosphate-technetium 99m. 367 cases].", "content": "Pyrophosphate-99m Tc injected intravenously is almost invariably fixed in the infarcted zone in transmural infarctions less than 8 days old. Fixation occurs in only 2/3 of cases of rudimentary infarction. The degree of fixation is more or less proportional to the size of the peak of creatine phosphokinase. After the 8th day following infarction, fixation is slight or nil. It is inconstant in pre-infarction syndrome or simple angina. This examination complements clinical, electrocardiographic and enzyme findings, in particular in the case of difficult diagnosis.", "contents": "[Scanning of the myocardium with pyrophosphate-technetium 99m. 367 cases]. Pyrophosphate-99m Tc injected intravenously is almost invariably fixed in the infarcted zone in transmural infarctions less than 8 days old. Fixation occurs in only 2/3 of cases of rudimentary infarction. The degree of fixation is more or less proportional to the size of the peak of creatine phosphokinase. After the 8th day following infarction, fixation is slight or nil. It is inconstant in pre-infarction syndrome or simple angina. This examination complements clinical, electrocardiographic and enzyme findings, in particular in the case of difficult diagnosis."}
{"id": "PMID:194221", "title": "[Scintigraphy using Technetium 99 m pyrophosphate in detection of bone metastasis of breast cancers. Analysis of 310 examinations].", "content": "Three hundred and ten bone scintigraphies were carried out in patients with a carcinoma of the breast. The results of these studies were compared not only with radiological findings but also the clinical and paraclinical course of the patients, the period of observation being between 8 and 44 months. Amongst the scintigrams in which no abnormality was detected, approximately 3.3% were obtained in patients with osteolytic metastases, the majority of these patients also having a rapidly growing primary tumourmamongst the patients with zones of hyperfixation and, at the same time, non-fixing metastases, 14/22 diedvery rapidly with diffuse bone metastases, this confirming the notion of poor prognosis in this \"false negative\" group. 11.3% of the abnormal results involved patients who showed no bone lesions more than 6 months after radio-isotopic examination \"false positives\". Of these, 12/18 were single lessions (41%). 14% of examinations carried out on a routine basis demonstrated metastases for which clinical and/or radiological confirmation was obtained only 2 to 9 months later.", "contents": "[Scintigraphy using Technetium 99 m pyrophosphate in detection of bone metastasis of breast cancers. Analysis of 310 examinations]. Three hundred and ten bone scintigraphies were carried out in patients with a carcinoma of the breast. The results of these studies were compared not only with radiological findings but also the clinical and paraclinical course of the patients, the period of observation being between 8 and 44 months. Amongst the scintigrams in which no abnormality was detected, approximately 3.3% were obtained in patients with osteolytic metastases, the majority of these patients also having a rapidly growing primary tumourmamongst the patients with zones of hyperfixation and, at the same time, non-fixing metastases, 14/22 diedvery rapidly with diffuse bone metastases, this confirming the notion of poor prognosis in this \"false negative\" group. 11.3% of the abnormal results involved patients who showed no bone lesions more than 6 months after radio-isotopic examination \"false positives\". Of these, 12/18 were single lessions (41%). 14% of examinations carried out on a routine basis demonstrated metastases for which clinical and/or radiological confirmation was obtained only 2 to 9 months later."}
{"id": "PMID:194222", "title": "Heterogeneity of 5' -termini of nucleolar 45S, 32S and 28S RNA in mouse hepatoma.", "content": "The 5'-termini of nucleolar 45S, 32S and 28S RNA's were analyzed by means of thin layer chromatography and Dowex-1 colum chromatography. 45S RNA did not bear a triphosphate at the 5'-terminus, but various monophosphates are found. 5'-termini of 32S and 28S RNA's were also heterogeneous. These results indicate that 45S molecules as isolated with the conventional procedure may not contains the primary transcript of the ribosomal gene, but a collection of large precursors with different degrees of processing at the 5'-terminus. The processing of the primary transcript may thus involve some unknown trimming processes at the 5'-terminus before the first major cleavage takes place.", "contents": "Heterogeneity of 5' -termini of nucleolar 45S, 32S and 28S RNA in mouse hepatoma. The 5'-termini of nucleolar 45S, 32S and 28S RNA's were analyzed by means of thin layer chromatography and Dowex-1 colum chromatography. 45S RNA did not bear a triphosphate at the 5'-terminus, but various monophosphates are found. 5'-termini of 32S and 28S RNA's were also heterogeneous. These results indicate that 45S molecules as isolated with the conventional procedure may not contains the primary transcript of the ribosomal gene, but a collection of large precursors with different degrees of processing at the 5'-terminus. The processing of the primary transcript may thus involve some unknown trimming processes at the 5'-terminus before the first major cleavage takes place."}
{"id": "PMID:194223", "title": "Specificity of DNA basic polypeptide interactions. II+ Influence of aromatic amino acid residues investigated with agarose bound lysine copolypeptides.", "content": "Binding affinities towards DNA and base pair specificities of lysine copolymers, containing different amounts of Phe, Tyr or Trp residues, were estimated using a previously described chromatographic method. Incorporation of few aromatic residues into polylysine causes a decrease in the binding affinity, however, further raising the aromatic residue - lysine ratio results in a continous increase of affinity, which is most pronounced with the Tyr copolymers and not observed with polymers containing neutral aliphatic amino acid residues. AT-specificity increases concomitant with binding affinity in the case of the Tyr copolymers but not with the Phe copolymers. The interaction of DNA with the alternating Phe-Lys polymer is significantly stronger than with the random copolymer of equal residue composition. The molecular and conformational reasons determining specificity are discussed.", "contents": "Specificity of DNA basic polypeptide interactions. II+ Influence of aromatic amino acid residues investigated with agarose bound lysine copolypeptides. Binding affinities towards DNA and base pair specificities of lysine copolymers, containing different amounts of Phe, Tyr or Trp residues, were estimated using a previously described chromatographic method. Incorporation of few aromatic residues into polylysine causes a decrease in the binding affinity, however, further raising the aromatic residue - lysine ratio results in a continous increase of affinity, which is most pronounced with the Tyr copolymers and not observed with polymers containing neutral aliphatic amino acid residues. AT-specificity increases concomitant with binding affinity in the case of the Tyr copolymers but not with the Phe copolymers. The interaction of DNA with the alternating Phe-Lys polymer is significantly stronger than with the random copolymer of equal residue composition. The molecular and conformational reasons determining specificity are discussed."}
{"id": "PMID:194224", "title": "The control of SV40 transcription during a lytic infection: late RNA synthesis in the presence of inhibitors of DNA replication.", "content": "The transition from early to late transcription of SV40 DNA in productively infected BSC-1 cells was analyzed using both inhibitors of DNA replication, and early (Group A) temperature sensitive (ts) mutants of SV40. Late virus specific cytoplasmic RNA sedimenting at 16S in neutral sucrose gradients and complementary to the plus (L) DNA strand of SV40 was detected in cultures infected in the presence of three inhibitors of DNA replication (Ara-C, FdU, and chloroquine), even though the inhibition of viral DNA replication appeared to be essentially complete. After infection with the early SV40 mutant tsA58, no DNA replication was detected at the restrictive temperature (41 degrees C) and no significant late RNA complementary to the plus (L) strand was found, in either the cytoplasm or nuclei of infected cells. These data support the concept that expression of late viral functions requires the initiation of viral DNA synthesis or a functional gene A protein, or both.", "contents": "The control of SV40 transcription during a lytic infection: late RNA synthesis in the presence of inhibitors of DNA replication. The transition from early to late transcription of SV40 DNA in productively infected BSC-1 cells was analyzed using both inhibitors of DNA replication, and early (Group A) temperature sensitive (ts) mutants of SV40. Late virus specific cytoplasmic RNA sedimenting at 16S in neutral sucrose gradients and complementary to the plus (L) DNA strand of SV40 was detected in cultures infected in the presence of three inhibitors of DNA replication (Ara-C, FdU, and chloroquine), even though the inhibition of viral DNA replication appeared to be essentially complete. After infection with the early SV40 mutant tsA58, no DNA replication was detected at the restrictive temperature (41 degrees C) and no significant late RNA complementary to the plus (L) strand was found, in either the cytoplasm or nuclei of infected cells. These data support the concept that expression of late viral functions requires the initiation of viral DNA synthesis or a functional gene A protein, or both."}
{"id": "PMID:194225", "title": "Nucleotide sequence of the restriction fragment Hind F-Eco RI2 of SV40 DNA.", "content": "The nucleotide sequence of the SV40 genome region between the Hind K fragment and the Eco RI cleavage site has been determined by a combination of three different approaches : analysis of RNA products obtained by transcription with Escherichia coli DNA dependent RNA polymerase, partial degradations with snake venom exonuclease and base-specific chemical degradation of 5'-terminal labeled restriction fragments. This nucleotide sequence shows only one open reading frame and allows the deduction of a small segment of the amino acid sequence of VP1, the major structural protein.", "contents": "Nucleotide sequence of the restriction fragment Hind F-Eco RI2 of SV40 DNA. The nucleotide sequence of the SV40 genome region between the Hind K fragment and the Eco RI cleavage site has been determined by a combination of three different approaches : analysis of RNA products obtained by transcription with Escherichia coli DNA dependent RNA polymerase, partial degradations with snake venom exonuclease and base-specific chemical degradation of 5'-terminal labeled restriction fragments. This nucleotide sequence shows only one open reading frame and allows the deduction of a small segment of the amino acid sequence of VP1, the major structural protein."}
{"id": "PMID:194226", "title": "Nucleotide sequence of the SV40 DNA restriction fragment Hind C-Hap 2.", "content": "We here report the nucleotide sequence of the SV40 DNA fragment Hind C - Hap 2. The fragment was labeled at the 5'-ends by means of polynucleotide kinase and gamma-(32P) ATP and digested with a suitable restriction enzyme. The separated products were then partially degraded with the base-specific reagents dimethyl-sulphate or hydrazine followed by direct analysis on polyacrylamide gel. The Hind C - Hap 2 sequence is 126 base pairs long and one of the three possible reading frames for translation does not contain any termination codon. So, although no protein is known to be encoded by this region, the possibility cannot yet be completely ruled out. The sequence also contains several AT-rich blocks.", "contents": "Nucleotide sequence of the SV40 DNA restriction fragment Hind C-Hap 2. We here report the nucleotide sequence of the SV40 DNA fragment Hind C - Hap 2. The fragment was labeled at the 5'-ends by means of polynucleotide kinase and gamma-(32P) ATP and digested with a suitable restriction enzyme. The separated products were then partially degraded with the base-specific reagents dimethyl-sulphate or hydrazine followed by direct analysis on polyacrylamide gel. The Hind C - Hap 2 sequence is 126 base pairs long and one of the three possible reading frames for translation does not contain any termination codon. So, although no protein is known to be encoded by this region, the possibility cannot yet be completely ruled out. The sequence also contains several AT-rich blocks."}
{"id": "PMID:194227", "title": "The sequence specificity of vertebrate DNA methylation.", "content": "The relative quantity of 5-methyl cytosine in vertebrate nuclear DNA shows species and tissue variation. To determine whether this is due to the action of species or cell specific DNA methylases the sequence specificity of the 5-methyl cytosine distribution in the DNA of a range of cells has been partially characterised. The pattern of methylation was found to be remarkably constant and indicates stringent evolutionary conservation of the characteristics of vertebrate DNA methylation.", "contents": "The sequence specificity of vertebrate DNA methylation. The relative quantity of 5-methyl cytosine in vertebrate nuclear DNA shows species and tissue variation. To determine whether this is due to the action of species or cell specific DNA methylases the sequence specificity of the 5-methyl cytosine distribution in the DNA of a range of cells has been partially characterised. The pattern of methylation was found to be remarkably constant and indicates stringent evolutionary conservation of the characteristics of vertebrate DNA methylation."}
{"id": "PMID:194228", "title": "Histone Hl-DNA interaction. Influence of phosphorylation on the interaction of histone Hl with linear fragmented DNA.", "content": "By measuring the fluorescence polarization of fluorescent histone H1 derivatives complexed with DNA, binding of the histone to DNA was studied as a function of ionic strength in the solution prior to and after the H1 phosphorylation on Ser-37 residue. Fluorescent labels were covalently linked either specifically to Tyr-72 residues or unspecifically to lysine residues in the H1 polypeptide chain. The values of the corresponding rotational relaxation times showed that at low ionic strength all the segments of the H1 molecule were immobilized on binding to DNA. The gradual increasing NaC1 concentration in the solution of H1-DNA complex was accompanied at first by additional retardation of the histone mobility in the complex, and then by progressive release of histone H1 from from the complex which was completed at 0.5-0.6 M NaC1 irrespective of phosphorylation. tat the same time the phosphorylation of histone H1 led to removal of the central and, presumably, N-terminal regions of H1 from DNA.", "contents": "Histone Hl-DNA interaction. Influence of phosphorylation on the interaction of histone Hl with linear fragmented DNA. By measuring the fluorescence polarization of fluorescent histone H1 derivatives complexed with DNA, binding of the histone to DNA was studied as a function of ionic strength in the solution prior to and after the H1 phosphorylation on Ser-37 residue. Fluorescent labels were covalently linked either specifically to Tyr-72 residues or unspecifically to lysine residues in the H1 polypeptide chain. The values of the corresponding rotational relaxation times showed that at low ionic strength all the segments of the H1 molecule were immobilized on binding to DNA. The gradual increasing NaC1 concentration in the solution of H1-DNA complex was accompanied at first by additional retardation of the histone mobility in the complex, and then by progressive release of histone H1 from from the complex which was completed at 0.5-0.6 M NaC1 irrespective of phosphorylation. tat the same time the phosphorylation of histone H1 led to removal of the central and, presumably, N-terminal regions of H1 from DNA."}
{"id": "PMID:194229", "title": "Nursing care of patients with viral hepatitis.", "content": "The nurse's role in the care of clients with acute viral hepatitis is based upon a nursing assessment of the client and his family system, diagnosis and planning for the individual needs of the client, and anticipatory guidance related to the client's return to the family and community.", "contents": "Nursing care of patients with viral hepatitis. The nurse's role in the care of clients with acute viral hepatitis is based upon a nursing assessment of the client and his family system, diagnosis and planning for the individual needs of the client, and anticipatory guidance related to the client's return to the family and community."}
{"id": "PMID:194233", "title": "Covalent attachment of peptides to cytochrome C for automated sequence determination.", "content": "Because small peptides are lost into the organic solvents used, it is virtually impossible to obtain the complete amino acid sequence of a small peptide using only an automated peptide sequencer of the spinning cup type. To overcome this problem we have extended peptides at the carboxy terminus by attachment to equine cytochrome c by a water soluble carbodiimide, relying on the acetylated N-terminus of the cytochrome to minimize its direct contribution to recovery of PTH-amino acids. The Model Peptide H-Leu-Trp-Met-Arg-phe-Ala-OH was used for most experiments. After reaction of 3H-peptide with cytochrome c, about one-third of the tritium counts migrated with cytochrome c during gel filtration. After attachment, the amino acid sequence of the hexapeptide was readily determined with a single cleavage Quadrol program in a Beckman 890B sequencer, whereas only the N-terminal residue was recovered without attachment. The repetitive yield after attachment was 95-96%, with 21-27+ overlap and an initial yield of 18-20%. Sequence data with other peptides illustrate applications and present limitations of our approach.", "contents": "Covalent attachment of peptides to cytochrome C for automated sequence determination. Because small peptides are lost into the organic solvents used, it is virtually impossible to obtain the complete amino acid sequence of a small peptide using only an automated peptide sequencer of the spinning cup type. To overcome this problem we have extended peptides at the carboxy terminus by attachment to equine cytochrome c by a water soluble carbodiimide, relying on the acetylated N-terminus of the cytochrome to minimize its direct contribution to recovery of PTH-amino acids. The Model Peptide H-Leu-Trp-Met-Arg-phe-Ala-OH was used for most experiments. After reaction of 3H-peptide with cytochrome c, about one-third of the tritium counts migrated with cytochrome c during gel filtration. After attachment, the amino acid sequence of the hexapeptide was readily determined with a single cleavage Quadrol program in a Beckman 890B sequencer, whereas only the N-terminal residue was recovered without attachment. The repetitive yield after attachment was 95-96%, with 21-27+ overlap and an initial yield of 18-20%. Sequence data with other peptides illustrate applications and present limitations of our approach."}
{"id": "PMID:194234", "title": "Purification of thioredoxin reductase from the Novikoff rat tumor.", "content": "Thioredoxin reductase (E.C.1.6.4.5.) has been purified to about 95% homogeneity from the Novikoff ascites rat tumor. The enzyme contained two subunits of approximately 58,000 daltons, with one FAD per subunit. The amino acid analysis is reported. An immunoadsorbent was prepared and used for affinity chromatography in order to improve the yield of the enzyme.", "contents": "Purification of thioredoxin reductase from the Novikoff rat tumor. Thioredoxin reductase (E.C.1.6.4.5.) has been purified to about 95% homogeneity from the Novikoff ascites rat tumor. The enzyme contained two subunits of approximately 58,000 daltons, with one FAD per subunit. The amino acid analysis is reported. An immunoadsorbent was prepared and used for affinity chromatography in order to improve the yield of the enzyme."}
{"id": "PMID:194235", "title": "[Characteristics of extracellular proteolytic enzymes of Actinomyces fradiae 0072].", "content": "The composition of extracellular proteinases from Actinomyces fradiae 0072 and their effect on proteins and synthetic substrates were studied. The enzyme preparation was found to have keratinolytic, caseinolytic, collagenolytic, collagenase, trypsin-like, carboxy- and aminopeptidase activities. Five low molecular weight proteinases capable to hydrolyse keratin, casein, azocollagen were obtained via fractionation of the enzyme preparation on DEAE-cellulose and Sephadex columns. Proteinases from Act. fradiae and aminopeptidase with a molecular weight of 31,000 were shown to be different enzymes. In hydrolysis of L-leucyl-2-naphthylamide the Michaelis constant and Vmax of the enzyme were found to be 3.02 X 10(-3) M and 0.35 X 10(2) micronM/ml-min, respectively.", "contents": "[Characteristics of extracellular proteolytic enzymes of Actinomyces fradiae 0072]. The composition of extracellular proteinases from Actinomyces fradiae 0072 and their effect on proteins and synthetic substrates were studied. The enzyme preparation was found to have keratinolytic, caseinolytic, collagenolytic, collagenase, trypsin-like, carboxy- and aminopeptidase activities. Five low molecular weight proteinases capable to hydrolyse keratin, casein, azocollagen were obtained via fractionation of the enzyme preparation on DEAE-cellulose and Sephadex columns. Proteinases from Act. fradiae and aminopeptidase with a molecular weight of 31,000 were shown to be different enzymes. In hydrolysis of L-leucyl-2-naphthylamide the Michaelis constant and Vmax of the enzyme were found to be 3.02 X 10(-3) M and 0.35 X 10(2) micronM/ml-min, respectively."}
{"id": "PMID:194239", "title": "On the bonding of FeO2 in hemoglobin and related dioxygen complexes.", "content": "The celebrated Fe(II)0(2) versus Fe(III) (02-) debate over the formal representation of the Fe02 moiety in hemoglobin can be resolved by consideration of the utility of each formalism. In the context of rationalizing the gross structural and electronic features of end-bound dioxygen, particularly in light of a new closely related chromium complex, the M(III)-(02-) formulation is both chemically reasonable and most useful. In conjunction with a qualitative molecular orbital overlap picture, the differing magnetic states of enc-bound M02 complexes and other geometrical features can be rationalized or predicted.", "contents": "On the bonding of FeO2 in hemoglobin and related dioxygen complexes. The celebrated Fe(II)0(2) versus Fe(III) (02-) debate over the formal representation of the Fe02 moiety in hemoglobin can be resolved by consideration of the utility of each formalism. In the context of rationalizing the gross structural and electronic features of end-bound dioxygen, particularly in light of a new closely related chromium complex, the M(III)-(02-) formulation is both chemically reasonable and most useful. In conjunction with a qualitative molecular orbital overlap picture, the differing magnetic states of enc-bound M02 complexes and other geometrical features can be rationalized or predicted."}
{"id": "PMID:194236", "title": "[Change in the activity of lysosomal collagenase during autolysis of intramuscular connective tissue].", "content": "Changes in the total, free and bound activity of collagenase of the intramuscular connective tissue were studied during beef muscle maturation (2 degrees C). Lysosomes were isolated by differential centrifugation. The studies showed a relatively rapid release of collagenase from lysosomes and a comparatively high stability of the enzyme during slow autolysis of muscles.", "contents": "[Change in the activity of lysosomal collagenase during autolysis of intramuscular connective tissue]. Changes in the total, free and bound activity of collagenase of the intramuscular connective tissue were studied during beef muscle maturation (2 degrees C). Lysosomes were isolated by differential centrifugation. The studies showed a relatively rapid release of collagenase from lysosomes and a comparatively high stability of the enzyme during slow autolysis of muscles."}
{"id": "PMID:194240", "title": "Lipid-protein interaction in the phosphatidylcholine exchange protein.", "content": "Incorporation of 2-acyl spin-labeled lecithin into the phosphatidylcholine protein from bovine liver results in an immobilization of the spin-label at the methyl and the carboxyl terminal end of the acyl chain. The nitroxide group on the protein-bound lecithin molecule is not accessible to ascorbate. This suggests that lecithin is buried in a pocket on the protein, which effectively shields the acyl chains from the medium.", "contents": "Lipid-protein interaction in the phosphatidylcholine exchange protein. Incorporation of 2-acyl spin-labeled lecithin into the phosphatidylcholine protein from bovine liver results in an immobilization of the spin-label at the methyl and the carboxyl terminal end of the acyl chain. The nitroxide group on the protein-bound lecithin molecule is not accessible to ascorbate. This suggests that lecithin is buried in a pocket on the protein, which effectively shields the acyl chains from the medium."}
{"id": "PMID:194237", "title": "[Cobalamin levels in rats with transplanted Zajdela ascites hepatoma].", "content": "The level of cobalamines in the kidney and liver of healthy rats and rats with implanted Zajdela ascites hepatoma (ZAH) was examined. The results were compared with the data obtained from the rats with sarcoma M-1. It was shown that different tumors had dissimilar effects upon the level of total cobalamines. However, the ratio of free cobalamines to protein-bound cobalamines (cobalamine-protein complexes) varied. The concentration of cobalamine-protein complexes increased in the liver, kidney and in the tumor. The experiments with ZAH demonstrated that ZAH cells contained appreciable amounts of cobalamines, whereas the supernatant contained only a minor quantity of cobalamines. Injections of 5'-deoxyadenosyl-B12 increased the level of cobalamines in ZAH cells and had a low effect on the level of cobalamines in the supernatant.", "contents": "[Cobalamin levels in rats with transplanted Zajdela ascites hepatoma]. The level of cobalamines in the kidney and liver of healthy rats and rats with implanted Zajdela ascites hepatoma (ZAH) was examined. The results were compared with the data obtained from the rats with sarcoma M-1. It was shown that different tumors had dissimilar effects upon the level of total cobalamines. However, the ratio of free cobalamines to protein-bound cobalamines (cobalamine-protein complexes) varied. The concentration of cobalamine-protein complexes increased in the liver, kidney and in the tumor. The experiments with ZAH demonstrated that ZAH cells contained appreciable amounts of cobalamines, whereas the supernatant contained only a minor quantity of cobalamines. Injections of 5'-deoxyadenosyl-B12 increased the level of cobalamines in ZAH cells and had a low effect on the level of cobalamines in the supernatant."}
{"id": "PMID:194241", "title": "In vitro synthesis of messenger RNA by a defective interfering particle of vesicular stomatitis virus.", "content": "A defective interfering particle derived from the heat-resistant strain of vesicular stomatitis virus was analyzed for the presence of virion-associated RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) activtiy. The RNA synthesizing capacity of the defective particles in vitro was similar to that of the wild-type virus. Characterization of the RNA produced in vitro indicated that the defective particles were able to synthesize vesicular stomatitis virus leader RNA and four virus mRNA species that sediment at 12-18 S. These RNA products were identical to the mRNAs synthesized in vitro by the wild-type virus in regard to size, polyadenylation, capping, and methylation. In contrast to the wild-type virus, the purified defective particles did not synthesize the large mRNA species sedimenting at 31 S in vitro. Possible mechanisms of homotypic and heterotypic interferences shown by this defective particle are discussed.", "contents": "In vitro synthesis of messenger RNA by a defective interfering particle of vesicular stomatitis virus. A defective interfering particle derived from the heat-resistant strain of vesicular stomatitis virus was analyzed for the presence of virion-associated RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) activtiy. The RNA synthesizing capacity of the defective particles in vitro was similar to that of the wild-type virus. Characterization of the RNA produced in vitro indicated that the defective particles were able to synthesize vesicular stomatitis virus leader RNA and four virus mRNA species that sediment at 12-18 S. These RNA products were identical to the mRNAs synthesized in vitro by the wild-type virus in regard to size, polyadenylation, capping, and methylation. In contrast to the wild-type virus, the purified defective particles did not synthesize the large mRNA species sedimenting at 31 S in vitro. Possible mechanisms of homotypic and heterotypic interferences shown by this defective particle are discussed."}
{"id": "PMID:194238", "title": "[Ketometabolite of vitamine A, its structure and enzymatic transformation].", "content": "The structure and enzymatic transformations of vitamin A keto-metabolite isolated from the rat liver were investigated. With the aid of physico-chemical methods, using isotopes 3/ and 18O, PMR and mass-spectrometry it was demonstrated that the metabolite was an ester of 4-keto-retinol with palmitic acid. The structure of 4-keto-retinal was confirmed by the chemical synthesis and by the enzymatic production of its derivatives. Under the influence of alcohol dehydrogenase 4-keto-retinol in the presence of NAD transformed into 4-keto-retinal which was oxidized into 4-keto-retinoic acid with the participation ofaldehyde oxidase. Similar oxidative enzymatic transformations occurred with the reduced form of the metabolite--4-hydroxyretinol. All the products were characterized in detail. Metabolism of 4-keto-retinyl-palmitate in vivo is realized via the same pathway as metabolism of retinyl-palmitate. The general pattern of oxidation of beta-ionone ring in position 4 of vitamin A and carotenoids is discussed.", "contents": "[Ketometabolite of vitamine A, its structure and enzymatic transformation]. The structure and enzymatic transformations of vitamin A keto-metabolite isolated from the rat liver were investigated. With the aid of physico-chemical methods, using isotopes 3/ and 18O, PMR and mass-spectrometry it was demonstrated that the metabolite was an ester of 4-keto-retinol with palmitic acid. The structure of 4-keto-retinal was confirmed by the chemical synthesis and by the enzymatic production of its derivatives. Under the influence of alcohol dehydrogenase 4-keto-retinol in the presence of NAD transformed into 4-keto-retinal which was oxidized into 4-keto-retinoic acid with the participation ofaldehyde oxidase. Similar oxidative enzymatic transformations occurred with the reduced form of the metabolite--4-hydroxyretinol. All the products were characterized in detail. Metabolism of 4-keto-retinyl-palmitate in vivo is realized via the same pathway as metabolism of retinyl-palmitate. The general pattern of oxidation of beta-ionone ring in position 4 of vitamin A and carotenoids is discussed."}
{"id": "PMID:194242", "title": "Sendai virus-induced hemolysis: reduction in heterogeneity of erythrocyte lipid bilayer fluidity.", "content": "Hemolysis of human or chicken erythrocytes by Sendai virus causes a change in the structure of the erythrocyte membrane lipid bilayer that can be detected by spin label electron spin resonance. In the intact erythrocyte, the phosphatidylcholine derivative spin label exists in a more rigid environment than the corresponding phosphatidylethanolamine label. Virus-induced hemolysis tends to abolish this difference in fluidity, i.e., the region of the phosphatidylcholine spin label becomes more fluid and that of the phosphatidylethanolamine spin label becomes more rigid. Fatty acid derivative spin labels, which may detect some \"average\" environment, show no change in fluidity. The fluidity change is detected at several different positions in the fatty acyl chain of the phosphatidylcholine spin label. Sendai virions grown in Madin-Darby bovine kidney (MDBK) cells or grown in eggs and harvested early, which lack hemolytic activity, cause no significant change in bilayer structure. Hemolytic activity and the ability to alter erythrocyte bilayer fluidity can be activated in MDBK-grown Sendai virions by trypsin treatment in vitro and in early-harvest egg-grown Sendai virions by freezing and thawing. Erythrocyte ghosts prepared by osmotic hemolysis and resealed by treatment with Mg2+ or elevated ionic strength exhibit a difference in fluidity between phosphatidylcholine and phosphatidylethanolamine spin labels, although less than that observed in whole cells. Incubation of resealed ghosts with Sendai virus abolishes the difference in fluidity. Unsealed ghosts that have been extensively washed show no heterogeneity in membrane bilayer fluidity, and incubation with Sendai virus causes no further fluidity change. Virus-induced hemolysis as measured by hemoglobin release is more sensitive to inhibition by Ca2+ than is the associated fluidity change in the bilayer.", "contents": "Sendai virus-induced hemolysis: reduction in heterogeneity of erythrocyte lipid bilayer fluidity. Hemolysis of human or chicken erythrocytes by Sendai virus causes a change in the structure of the erythrocyte membrane lipid bilayer that can be detected by spin label electron spin resonance. In the intact erythrocyte, the phosphatidylcholine derivative spin label exists in a more rigid environment than the corresponding phosphatidylethanolamine label. Virus-induced hemolysis tends to abolish this difference in fluidity, i.e., the region of the phosphatidylcholine spin label becomes more fluid and that of the phosphatidylethanolamine spin label becomes more rigid. Fatty acid derivative spin labels, which may detect some \"average\" environment, show no change in fluidity. The fluidity change is detected at several different positions in the fatty acyl chain of the phosphatidylcholine spin label. Sendai virions grown in Madin-Darby bovine kidney (MDBK) cells or grown in eggs and harvested early, which lack hemolytic activity, cause no significant change in bilayer structure. Hemolytic activity and the ability to alter erythrocyte bilayer fluidity can be activated in MDBK-grown Sendai virions by trypsin treatment in vitro and in early-harvest egg-grown Sendai virions by freezing and thawing. Erythrocyte ghosts prepared by osmotic hemolysis and resealed by treatment with Mg2+ or elevated ionic strength exhibit a difference in fluidity between phosphatidylcholine and phosphatidylethanolamine spin labels, although less than that observed in whole cells. Incubation of resealed ghosts with Sendai virus abolishes the difference in fluidity. Unsealed ghosts that have been extensively washed show no heterogeneity in membrane bilayer fluidity, and incubation with Sendai virus causes no further fluidity change. Virus-induced hemolysis as measured by hemoglobin release is more sensitive to inhibition by Ca2+ than is the associated fluidity change in the bilayer."}
{"id": "PMID:194243", "title": "Pineal protein phosphorylation during serotonin N-acetyltransferase induction.", "content": "The activity of soluble protein kinase (ATP:protein phosphotransferase,EC 2.7.1.37) and pattern of nuclear protein phosphorylation was monitored in cultured rat pineal glands during the induction of serotonin N-acetyltransferase (acetyl-CoA:serotonin N-acetyltransferase;EC 2.3.1.5)by l-isoproterenol. A nuclear protein appears to be phosphorylated during the early stages of enzyme induction but is not phosphorylated at later stages of induction. This correlates well with the need for RNA synthesis associated with the induction process. The nuclear protein was also phosphorylated when the pineal glands were treated with dibutyryl 3':5'-cyclic AMP. The soluble protein kinase activity appeared to decline during mid-to-late stages of enzyme induction, but there was no concomitant increase in the particulate protein kinase activity.", "contents": "Pineal protein phosphorylation during serotonin N-acetyltransferase induction. The activity of soluble protein kinase (ATP:protein phosphotransferase,EC 2.7.1.37) and pattern of nuclear protein phosphorylation was monitored in cultured rat pineal glands during the induction of serotonin N-acetyltransferase (acetyl-CoA:serotonin N-acetyltransferase;EC 2.3.1.5)by l-isoproterenol. A nuclear protein appears to be phosphorylated during the early stages of enzyme induction but is not phosphorylated at later stages of induction. This correlates well with the need for RNA synthesis associated with the induction process. The nuclear protein was also phosphorylated when the pineal glands were treated with dibutyryl 3':5'-cyclic AMP. The soluble protein kinase activity appeared to decline during mid-to-late stages of enzyme induction, but there was no concomitant increase in the particulate protein kinase activity."}
{"id": "PMID:194244", "title": "Primary structure of very low density apolipoprotein C-II of human plasma.", "content": "Apolipoprotein C-II (apoC-II), a protein constituent of very low density lipoproteins of human plasma and the activator protein of lipoprotein lipase, has been isolated and its amino acid sequence has been studied. The protein has 78 amino acid residues and is lacking cysteine, cystine, and histidine. Chromatography on Bio-Gel P-30 in 25% formic acid of the cyanogen bromide digest of apoC-II yields three fragments designated as CNBr-I, -II, and -III. They contained 50, 19, and 9 residues, respectively. The alignment of the cyanogen bromide fragments has been established as CNBr-III-I-II by isolation and sequence of the tryptic peptides of the intact protein. The amino acid sequences of the tryptic and CNBr peptides were determined by conventional methods. With this information, it was possible to establish the complete amino acid sequence of apoC-II.", "contents": "Primary structure of very low density apolipoprotein C-II of human plasma. Apolipoprotein C-II (apoC-II), a protein constituent of very low density lipoproteins of human plasma and the activator protein of lipoprotein lipase, has been isolated and its amino acid sequence has been studied. The protein has 78 amino acid residues and is lacking cysteine, cystine, and histidine. Chromatography on Bio-Gel P-30 in 25% formic acid of the cyanogen bromide digest of apoC-II yields three fragments designated as CNBr-I, -II, and -III. They contained 50, 19, and 9 residues, respectively. The alignment of the cyanogen bromide fragments has been established as CNBr-III-I-II by isolation and sequence of the tryptic peptides of the intact protein. The amino acid sequences of the tryptic and CNBr peptides were determined by conventional methods. With this information, it was possible to establish the complete amino acid sequence of apoC-II."}
{"id": "PMID:194245", "title": "Solid tumor models for assessment of different treatment modalities: therapeutic strategy for sequential chemotherapy with radiotherapy.", "content": "A therapeutic strategy for combined radiotherapy and chemotherapy of experimental solid tumors has been devised. More effective utilization of combined chemotherapy and radiotherapy may be realized clinically if comparable information is obtained in man. The overall treatment efficiency of successive courses of treatment has been determined by a method that defines tumor response quantitatively over an entire spectrum of tumor responses. The findings of this study have shown that an individual tumor that responds well to the first course of therapy will respond well to the second and third courses of combined modality therapy. Various solid tumors in different animal species have demonstrated variability of response to treatment, analogous to the many types of response found clinically.", "contents": "Solid tumor models for assessment of different treatment modalities: therapeutic strategy for sequential chemotherapy with radiotherapy. A therapeutic strategy for combined radiotherapy and chemotherapy of experimental solid tumors has been devised. More effective utilization of combined chemotherapy and radiotherapy may be realized clinically if comparable information is obtained in man. The overall treatment efficiency of successive courses of treatment has been determined by a method that defines tumor response quantitatively over an entire spectrum of tumor responses. The findings of this study have shown that an individual tumor that responds well to the first course of therapy will respond well to the second and third courses of combined modality therapy. Various solid tumors in different animal species have demonstrated variability of response to treatment, analogous to the many types of response found clinically."}
{"id": "PMID:194246", "title": "Cell-free synthesis of two proteins unique to RNA of transforming virions of Rous sarcoma virus.", "content": "We have utilized a reticulocyte lysate system to translate the 35S RNA of Rous sarcoma virus. Autoradiograms of the protein products separated on sodium dodecyl sulfate/polyacrylamide gels reveal a heterogeneous mixture of proteins of sizes ranging from 13,000 to 180,000 daltons. In comparing the translational products from 35S RNA of Prague B Rous sarcoma virus with those formed from the RNA of a transformation-defective deletion mutant derived from Prague B, we have found that two proteins, 25,000 and 18,000 daltons, are missing from the latter. Neither of these proteins is immunoprecipitated by monospecific antisera against the structural proteins of avian RNA tumor viruses. The combined atomic mass of 43,000 daltons corresponds to the amount of genetic coding capacity (40,000-50,000 daltons in terms of protein products) deleted from the RNA of the transformation-defective viruses. We propose that these proteins are coded for by the putative oncogene (onc) or sarc (src) gene and that one or both of them may be responsible for the oncogenic transformation caused by these viruses in infected cells.", "contents": "Cell-free synthesis of two proteins unique to RNA of transforming virions of Rous sarcoma virus. We have utilized a reticulocyte lysate system to translate the 35S RNA of Rous sarcoma virus. Autoradiograms of the protein products separated on sodium dodecyl sulfate/polyacrylamide gels reveal a heterogeneous mixture of proteins of sizes ranging from 13,000 to 180,000 daltons. In comparing the translational products from 35S RNA of Prague B Rous sarcoma virus with those formed from the RNA of a transformation-defective deletion mutant derived from Prague B, we have found that two proteins, 25,000 and 18,000 daltons, are missing from the latter. Neither of these proteins is immunoprecipitated by monospecific antisera against the structural proteins of avian RNA tumor viruses. The combined atomic mass of 43,000 daltons corresponds to the amount of genetic coding capacity (40,000-50,000 daltons in terms of protein products) deleted from the RNA of the transformation-defective viruses. We propose that these proteins are coded for by the putative oncogene (onc) or sarc (src) gene and that one or both of them may be responsible for the oncogenic transformation caused by these viruses in infected cells."}
{"id": "PMID:194247", "title": "Immune surveillance against virus-induced tumors and nonrejectability of spontaneous tumors: contrasting consequences of host versus tumor evolution.", "content": "Spontaneous tumours are defined as tumors that develop in the absence of all experimental interference. In contrast to the widely documented, strong rejection reactions against most virus-induced tumors, spontaneous tumors evoke little or no detectable rejection reaction in intact or preimmunized syngeneic hosts. The difference can be viewed in relation to the contrasting natural history of the two conditions. Spontaneous tumors evolve in several steps, as a fule. \"Tumor progression\" is a microevolutionary process at the level of the somatic tissue where successive clonal variants replace each other. Each new variant gains the upper hand due to its greater independence of some restricting host mechanism. Independence of immune restrictions must be part of this process. Host selection for immune resistance apparently plays no major role here, presumably because most of the naturally occurring tumors arise after the host has passed the peak of its reproductive period. Protection against the oncogenic effects of ubiquitous tumor viruses is, on the other hand, the result of host selection for immune mechanisms favoring prompt rejection of virus-transformed cells. This is neither synonymous with nor related to protection against the viral infection per se, which is frequently successful and usually quite harmless. A certain relationship can be perceived between the degree of viral ubiquity and the strength of immune protection against the corresponding tumor cells. Natural selection for host recognition of commonly occurring, virally induced changes in neoplastic cell membranes can be surmised to occur, at least in part, by the fixation of appropriate immune responsiveness (Ir) genes. The role of Ir genes for tumor recognition can be approached by the genetic analysis of the F1 hybrid resistance effect. Unresponsiveness to spontaneous tumors may be overcome by target-cell modification, e.g., by chemical coupling, somatic cell hybridization, or viral \"xenogenization\".", "contents": "Immune surveillance against virus-induced tumors and nonrejectability of spontaneous tumors: contrasting consequences of host versus tumor evolution. Spontaneous tumours are defined as tumors that develop in the absence of all experimental interference. In contrast to the widely documented, strong rejection reactions against most virus-induced tumors, spontaneous tumors evoke little or no detectable rejection reaction in intact or preimmunized syngeneic hosts. The difference can be viewed in relation to the contrasting natural history of the two conditions. Spontaneous tumors evolve in several steps, as a fule. \"Tumor progression\" is a microevolutionary process at the level of the somatic tissue where successive clonal variants replace each other. Each new variant gains the upper hand due to its greater independence of some restricting host mechanism. Independence of immune restrictions must be part of this process. Host selection for immune resistance apparently plays no major role here, presumably because most of the naturally occurring tumors arise after the host has passed the peak of its reproductive period. Protection against the oncogenic effects of ubiquitous tumor viruses is, on the other hand, the result of host selection for immune mechanisms favoring prompt rejection of virus-transformed cells. This is neither synonymous with nor related to protection against the viral infection per se, which is frequently successful and usually quite harmless. A certain relationship can be perceived between the degree of viral ubiquity and the strength of immune protection against the corresponding tumor cells. Natural selection for host recognition of commonly occurring, virally induced changes in neoplastic cell membranes can be surmised to occur, at least in part, by the fixation of appropriate immune responsiveness (Ir) genes. The role of Ir genes for tumor recognition can be approached by the genetic analysis of the F1 hybrid resistance effect. Unresponsiveness to spontaneous tumors may be overcome by target-cell modification, e.g., by chemical coupling, somatic cell hybridization, or viral \"xenogenization\"."}
{"id": "PMID:194248", "title": "Biogenesis of poxviruses: analysis of the morphogenetic sequence using a conditional lethal mutant defective in envelope self-assembly.", "content": "A conditional lethal, temperature-sensitive mutant of vaccinia, defective in assembly of the virus envelope and maturation, was characterized and shown to mimic exactly the aberrations produced by rifampicin. Analyses of the infection at restrictive and permissive temperatures were conducted with electron microscopy, isotopic pulse-chase experiments in which polypeptides were separated by polyacrylamide slab gels, and assays of core enzymatic activities. The data collected by several approaches reveal that assembly and maturation of vaccinia involves a tightly coupled sequence of interrelated events including the assembly of the envelope, post-translational cleavage of several virion polypeptides, and induction of the core enzymes.", "contents": "Biogenesis of poxviruses: analysis of the morphogenetic sequence using a conditional lethal mutant defective in envelope self-assembly. A conditional lethal, temperature-sensitive mutant of vaccinia, defective in assembly of the virus envelope and maturation, was characterized and shown to mimic exactly the aberrations produced by rifampicin. Analyses of the infection at restrictive and permissive temperatures were conducted with electron microscopy, isotopic pulse-chase experiments in which polypeptides were separated by polyacrylamide slab gels, and assays of core enzymatic activities. The data collected by several approaches reveal that assembly and maturation of vaccinia involves a tightly coupled sequence of interrelated events including the assembly of the envelope, post-translational cleavage of several virion polypeptides, and induction of the core enzymes."}
{"id": "PMID:194249", "title": "Opioid peptide enkephalin: immunohistochemical mapping in rat central nervous system.", "content": "Using specific antisera to methionine-enkephalin and leucine-enkephalin, we have visualized apparent enkephalin-containing neuronal fibers and terminals throughout the central nervous system of the rat. Immunoreactive enkephalin displays sharply defined localizations. Regions of highest immunofluorescent density include the laminae I and II of the spinal cord, the substantia gelatinosa of the caudal nucleus of nerve V, the vagal nuclei of the medulla, the periventricular and periaqueductal areas of the upper medulla and midbrain, dorsomedial thalamic regions, specific hypothalamic nuclei, the basal ganglia, particularly the globus pallidus and the central nucleus of the amygdala, and the lateral septum. In certain regions enkephalin immunofluorescence corresponds closely with the distribution of autoradiographic opiate receptor grains.", "contents": "Opioid peptide enkephalin: immunohistochemical mapping in rat central nervous system. Using specific antisera to methionine-enkephalin and leucine-enkephalin, we have visualized apparent enkephalin-containing neuronal fibers and terminals throughout the central nervous system of the rat. Immunoreactive enkephalin displays sharply defined localizations. Regions of highest immunofluorescent density include the laminae I and II of the spinal cord, the substantia gelatinosa of the caudal nucleus of nerve V, the vagal nuclei of the medulla, the periventricular and periaqueductal areas of the upper medulla and midbrain, dorsomedial thalamic regions, specific hypothalamic nuclei, the basal ganglia, particularly the globus pallidus and the central nucleus of the amygdala, and the lateral septum. In certain regions enkephalin immunofluorescence corresponds closely with the distribution of autoradiographic opiate receptor grains."}
{"id": "PMID:194250", "title": "3':5'-cyclic AMP and hormonal control of puparium formation in the fleshfly Sarcophaga bullata.", "content": "Injection of 3':5'-cyclic AMP (cAMP) into larvae of the fly Sarcophaga bullata 3-4 hr before the beginning of puparium formation (red-spiracle stage) greatly accelerates the onset of tanning without affecting initiation of puparium formation (anterior retraction). Accelerated tanning resembles real tanning in two important respects: the solubility of cuticular proteins becomes reduced and [U-14C]tyrosine is incorporated into the cuticle. Of a number of cAMP analogues tested, 3':5'- cyclic GMP, 2':3'-cyclic AMP, and 5'-AMP were inactive, dibutyryl-3':5'-cAMP had only slight activity, and cyclic IMP and deoxy-3':5'-cAMP showed some activity. Theophylline enhanced the effect of small doses of cAMP or of blood, diluted 1:8, active in the puparium tanning factor. Injection of dopa, dopamine, acetyldopamine, or epinephrine, but not of tyrosine, had an accelerating effect similar to that of cAMP. The tanning-inhibiting effect of DL-alpha-methyl-alpha-hydrazino-beta-(3,4-dihydroxyphenyl)propionic acid monohydrate is reversed by dopamine or epinephrine, but not by tyrosine, dopa, or cAMP. Evidence is presented to indicate that the responses to cAMP are not artifacts but reflect actual biochemical events during tanning.", "contents": "3':5'-cyclic AMP and hormonal control of puparium formation in the fleshfly Sarcophaga bullata. Injection of 3':5'-cyclic AMP (cAMP) into larvae of the fly Sarcophaga bullata 3-4 hr before the beginning of puparium formation (red-spiracle stage) greatly accelerates the onset of tanning without affecting initiation of puparium formation (anterior retraction). Accelerated tanning resembles real tanning in two important respects: the solubility of cuticular proteins becomes reduced and [U-14C]tyrosine is incorporated into the cuticle. Of a number of cAMP analogues tested, 3':5'- cyclic GMP, 2':3'-cyclic AMP, and 5'-AMP were inactive, dibutyryl-3':5'-cAMP had only slight activity, and cyclic IMP and deoxy-3':5'-cAMP showed some activity. Theophylline enhanced the effect of small doses of cAMP or of blood, diluted 1:8, active in the puparium tanning factor. Injection of dopa, dopamine, acetyldopamine, or epinephrine, but not of tyrosine, had an accelerating effect similar to that of cAMP. The tanning-inhibiting effect of DL-alpha-methyl-alpha-hydrazino-beta-(3,4-dihydroxyphenyl)propionic acid monohydrate is reversed by dopamine or epinephrine, but not by tyrosine, dopa, or cAMP. Evidence is presented to indicate that the responses to cAMP are not artifacts but reflect actual biochemical events during tanning."}
{"id": "PMID:194267", "title": "Drinking behavior in water deprived rats after angiotensin receptor blockade.", "content": "Angiotensin II is a peptide normally present in the bloodstream and central nervous system. Exogenous angiotensin induces drinking which is inhibited by saralasin, a specific receptor antagonist. Administration of saralasin does not reduce endogenously stimulated drinking. Angiotensin is dipsogenic after intravenous or intracerebroventricular infusion, raising the possibility of multiple access routes to the brain. Water deprived rats were given saralasin by both routes simultaneously to block the access of endogenous angiotensin to recentors reached from blood and ventricular cerebrospinal fluid (CSF). Water deprivation increased plasma (Na+), hematocrit, vasopressin content and renin activity but saralasin treatment did not reduce water intake after 30 or 60 min. Therefore, blood or CSF-bore angiotensin does not appear to be an absolute requirement for water deprivation drinking behavior.", "contents": "Drinking behavior in water deprived rats after angiotensin receptor blockade. Angiotensin II is a peptide normally present in the bloodstream and central nervous system. Exogenous angiotensin induces drinking which is inhibited by saralasin, a specific receptor antagonist. Administration of saralasin does not reduce endogenously stimulated drinking. Angiotensin is dipsogenic after intravenous or intracerebroventricular infusion, raising the possibility of multiple access routes to the brain. Water deprived rats were given saralasin by both routes simultaneously to block the access of endogenous angiotensin to recentors reached from blood and ventricular cerebrospinal fluid (CSF). Water deprivation increased plasma (Na+), hematocrit, vasopressin content and renin activity but saralasin treatment did not reduce water intake after 30 or 60 min. Therefore, blood or CSF-bore angiotensin does not appear to be an absolute requirement for water deprivation drinking behavior."}
{"id": "PMID:194273", "title": "Accuracy of computed tomography of the liver and biliary tract.", "content": "Computed tomography (CT) is a highly accurate method of detecting and clarifying the nature of space-occupying lesions within the liver. Obstructive (surgical) jaundice can be differentiated from nonobstructive (medical) jaundice very accurately using CT scanning; when obstruction is present, its level and cause can often be diagnosed. CT is not a sensitive method of detecting hepatocellular disease. Sources of error in CT scan interpretation are analyzed.", "contents": "Accuracy of computed tomography of the liver and biliary tract. Computed tomography (CT) is a highly accurate method of detecting and clarifying the nature of space-occupying lesions within the liver. Obstructive (surgical) jaundice can be differentiated from nonobstructive (medical) jaundice very accurately using CT scanning; when obstruction is present, its level and cause can often be diagnosed. CT is not a sensitive method of detecting hepatocellular disease. Sources of error in CT scan interpretation are analyzed."}
{"id": "PMID:194274", "title": "Cardiac localization of 99mTc-(Sn)-pyrophosphate following irradiation of the chest.", "content": "Of 70 consecutive cancer patients referred from radiotherapy for bone scans, 32% showed cardiac uptake of 99mTc-(Sn)-pyrophosphate; only 9% of a control group showed this uptake. Of those with prior left hemithorax irradiation, 60% showed cardiac uptake; only 12% of those with irradiation elsewhere showed this phenomenon (p less than .01). The patients who had no increased uptake tended to have shorter irradiation-to-scan time intervals (less than 10 months) than those who did show increased uptake (mean of 22 months).", "contents": "Cardiac localization of 99mTc-(Sn)-pyrophosphate following irradiation of the chest. Of 70 consecutive cancer patients referred from radiotherapy for bone scans, 32% showed cardiac uptake of 99mTc-(Sn)-pyrophosphate; only 9% of a control group showed this uptake. Of those with prior left hemithorax irradiation, 60% showed cardiac uptake; only 12% of those with irradiation elsewhere showed this phenomenon (p less than .01). The patients who had no increased uptake tended to have shorter irradiation-to-scan time intervals (less than 10 months) than those who did show increased uptake (mean of 22 months)."}
{"id": "PMID:194275", "title": "Ultrastructure and microanalysis of \"benign\" and \"malignant\" breast calcifications.", "content": "Differences in morphology between \"benign\" and \"malignant\" breast calcifications were observed in a pilot study utilizing scanning electron microscopy and x-ray analysis. Preliminary data suggest that there may also be chemical differences between calcifications and in the surrounding tissue.", "contents": "Ultrastructure and microanalysis of \"benign\" and \"malignant\" breast calcifications. Differences in morphology between \"benign\" and \"malignant\" breast calcifications were observed in a pilot study utilizing scanning electron microscopy and x-ray analysis. Preliminary data suggest that there may also be chemical differences between calcifications and in the surrounding tissue."}
{"id": "PMID:194276", "title": "Angiographic demonstration of growth of hepatocellular carcinoma in the hepatic vein and inferior vena cava.", "content": "A total of 141 patients with hepatocellular carcinoma were examined by selective celiac and hepatic arteriography. In 7 the so-called \"thread and streaks\" sign or its equivalent was observed along the vertebral column at the level of the diaphragm where the hepatic veins enter the inferior vena cava. Extensive tumor growth in the hepatic vein and invading the vena cava was confirmed by autopsy in 3 and hepatic venography in 1.", "contents": "Angiographic demonstration of growth of hepatocellular carcinoma in the hepatic vein and inferior vena cava. A total of 141 patients with hepatocellular carcinoma were examined by selective celiac and hepatic arteriography. In 7 the so-called \"thread and streaks\" sign or its equivalent was observed along the vertebral column at the level of the diaphragm where the hepatic veins enter the inferior vena cava. Extensive tumor growth in the hepatic vein and invading the vena cava was confirmed by autopsy in 3 and hepatic venography in 1."}
{"id": "PMID:194277", "title": "Delination of lesions of the base of the skull by computed tomography.", "content": "It is possible to delineate the extent of tumors related to the base of the skull by computed tomography in two planes. With current scanners, thin sections are possible and the artifacts produced by the bone are minimal. Bone and soft-tissue details can be visualized with clinically useful resolution. Precise evaluation of the extent of such lesions is important in determining surgical or radiotherapeutic approaches. Six illustrative cases are presented.", "contents": "Delination of lesions of the base of the skull by computed tomography. It is possible to delineate the extent of tumors related to the base of the skull by computed tomography in two planes. With current scanners, thin sections are possible and the artifacts produced by the bone are minimal. Bone and soft-tissue details can be visualized with clinically useful resolution. Precise evaluation of the extent of such lesions is important in determining surgical or radiotherapeutic approaches. Six illustrative cases are presented."}
{"id": "PMID:194286", "title": "Rat osteogenic sarcoma cells:effects of some prostaglandins, their metabolites and analogues on cyclic AMP production.", "content": "Cyclic AMP production by freshly isolated cells, from a 32P-induced transplantable rat osteogenic sarcoma, was stimulated by PGE1, PGE2 and to a less extent by PGF2alpha and PGA2. In the case of PGE2, the cyclic AMP content of cells was maximal within 5 min. The 13,14-dihydroderivatives of PGE1, PGE2 and PGF2alpha had approximately 40% of the activity of the parent prostaglandin whilst, in every case, the metabolites (15-keto and 13,14-dihydro-15-keto) had very little activity. Two prostaglandin endoperoxide analogues (U44069 and U46619) had only 10% of the activity of an equimolar dose of PGE2. The data presented in this paper demonstrates similarities between the responses of these cells and cells derived from bony tissue in terms of the ability of prostaglandins to stimulate bone resorption in tissue culture.", "contents": "Rat osteogenic sarcoma cells:effects of some prostaglandins, their metabolites and analogues on cyclic AMP production. Cyclic AMP production by freshly isolated cells, from a 32P-induced transplantable rat osteogenic sarcoma, was stimulated by PGE1, PGE2 and to a less extent by PGF2alpha and PGA2. In the case of PGE2, the cyclic AMP content of cells was maximal within 5 min. The 13,14-dihydroderivatives of PGE1, PGE2 and PGF2alpha had approximately 40% of the activity of the parent prostaglandin whilst, in every case, the metabolites (15-keto and 13,14-dihydro-15-keto) had very little activity. Two prostaglandin endoperoxide analogues (U44069 and U46619) had only 10% of the activity of an equimolar dose of PGE2. The data presented in this paper demonstrates similarities between the responses of these cells and cells derived from bony tissue in terms of the ability of prostaglandins to stimulate bone resorption in tissue culture."}
{"id": "PMID:194287", "title": "Relations between prostaglandin E2, F2alpha, and cyclic nucleotides levels in rat brain and induction of convulsions.", "content": "Fully convulsant doses of pentamethylenetetrazole cause marked increase in rat brain cortical PGF2alpha, PGE2, cGMP and cAMP during seizures, whereas subconvulsant doses cause an increase of rat brain cortical PGF2alpha without affecting the other biochemical parameters considered. Rat cerebellar prostaglandins were not modified by the convulsant agent at either dosage.", "contents": "Relations between prostaglandin E2, F2alpha, and cyclic nucleotides levels in rat brain and induction of convulsions. Fully convulsant doses of pentamethylenetetrazole cause marked increase in rat brain cortical PGF2alpha, PGE2, cGMP and cAMP during seizures, whereas subconvulsant doses cause an increase of rat brain cortical PGF2alpha without affecting the other biochemical parameters considered. Rat cerebellar prostaglandins were not modified by the convulsant agent at either dosage."}
{"id": "PMID:194291", "title": "[Care for single paraplegics by conscentious objectors (author's transl)].", "content": "A practical example shows that the rehabilitation of a single, dependent paraplegic cannot be terminated with the completion of the medical rehabilitation phase and the provision of an adequate job. The complete integration necessitates well organized care and assistance. In the described case this has been achieved by personal initiative, because for this problem complex there is a gap in the state rehabilitation system. Private care by conscentious objectors is described and put to discussion.", "contents": "[Care for single paraplegics by conscentious objectors (author's transl)]. A practical example shows that the rehabilitation of a single, dependent paraplegic cannot be terminated with the completion of the medical rehabilitation phase and the provision of an adequate job. The complete integration necessitates well organized care and assistance. In the described case this has been achieved by personal initiative, because for this problem complex there is a gap in the state rehabilitation system. Private care by conscentious objectors is described and put to discussion."}
{"id": "PMID:194293", "title": "[Proton relaxation times of water in normal and transformed cells infected with temperature sensitive virus mutants (author's transl)].", "content": "Nuclear magnetic resonance spin-lattice relaxation times (T1) of tissue water protons are elevated in samples from tumors when compared to the corresponding normal tissues. In order to exclude differences between the normal and the tumorous tissue samples other than transformation as far as possible the T1values of cells infected by temperature sensitive transforming mutants of Rous sarcoma virus were measured. In this model genetic homogeneity of the host cells as well as identity of the viruses in the normal and transformed state is assured. In the transformed cells the protons relaxed more slowly than in the cells of normal phenotype which were kept at an only slightly higher incubation temperature.", "contents": "[Proton relaxation times of water in normal and transformed cells infected with temperature sensitive virus mutants (author's transl)]. Nuclear magnetic resonance spin-lattice relaxation times (T1) of tissue water protons are elevated in samples from tumors when compared to the corresponding normal tissues. In order to exclude differences between the normal and the tumorous tissue samples other than transformation as far as possible the T1values of cells infected by temperature sensitive transforming mutants of Rous sarcoma virus were measured. In this model genetic homogeneity of the host cells as well as identity of the viruses in the normal and transformed state is assured. In the transformed cells the protons relaxed more slowly than in the cells of normal phenotype which were kept at an only slightly higher incubation temperature."}
{"id": "PMID:194294", "title": "The association of Wilms' tumor with second primary malignancies.", "content": "Medulloblastoma occurs uncommonly in the neonatal period. Metastatic Wilm's tumor in a newborn is extremely rare. The coincidence of these two neoplasms in one infant, and an equally uncommon combination of Wilms' tumor and a cerebellar medulloephithelioma in another child prompted this report. The authors speculate on the mechanism of oncogenesis in these and other infants with neonatal malignancies.", "contents": "The association of Wilms' tumor with second primary malignancies. Medulloblastoma occurs uncommonly in the neonatal period. Metastatic Wilm's tumor in a newborn is extremely rare. The coincidence of these two neoplasms in one infant, and an equally uncommon combination of Wilms' tumor and a cerebellar medulloephithelioma in another child prompted this report. The authors speculate on the mechanism of oncogenesis in these and other infants with neonatal malignancies."}
{"id": "PMID:194301", "title": "Prevalence of hyperlipoproteinemia in men with gallstone disease.", "content": "Lipoprotein disorders are associated with changes in the bile lipid composition, and gallstone disease has been reported to be common in hyperlipoproteinemic patients. To find out whether there is a significant correlation between hyperlipoproteinemia and gallstone disease, we compared the prealence of hyperlipoproteinemia in a consecutive series of male gallstone patients with that in an age-matched consecutive series of gallstone-free patients. The gallstone patients were hyperlipoproteinemic in 43.5% as compared with 22.5% in the control patients. This difference was statistically significant. Prebetahyperlipoproteinemia (type IV) was the most common lipoprotein disorder in gallstone patients as well as in control patients.", "contents": "Prevalence of hyperlipoproteinemia in men with gallstone disease. Lipoprotein disorders are associated with changes in the bile lipid composition, and gallstone disease has been reported to be common in hyperlipoproteinemic patients. To find out whether there is a significant correlation between hyperlipoproteinemia and gallstone disease, we compared the prealence of hyperlipoproteinemia in a consecutive series of male gallstone patients with that in an age-matched consecutive series of gallstone-free patients. The gallstone patients were hyperlipoproteinemic in 43.5% as compared with 22.5% in the control patients. This difference was statistically significant. Prebetahyperlipoproteinemia (type IV) was the most common lipoprotein disorder in gallstone patients as well as in control patients."}
{"id": "PMID:194305", "title": "[Pancreatic island cell tumors and their syndromes. I. Insulinomas, organic hypertinsulinism].", "content": "Based on a retrospective investigation of 61 surgical and autopsy specimens, the histopathologic features and clinical manifestations of islet cell tumors are described. In 33 cases reviewed in the first part of this study there existed indications of primary hyperinsulinism (HI) which was generally verified through fast test, stimulation tests or by insulin determination. In 25 cases the HI was caused by benign B-cell adenomas and in 3 cases by metastasizing carcinomas. In another case, polymacronesia of the pancreas with all patterns from abnormally structured islets to true adenomas was found. This patient was free of symptoms after subtotal pancreatectomy. In 4 other cases neither adenomas nor evident islet changes were identified; subtotal pancreatectomy cured only one patient. The insulinomas were surgically removed in 16 cases locally and in 9 cases by partial pancreatectomy. In two patients the adenomas were detected only after a second operation, and a third suffered from HI despite removal of two adenomas. The majority of insulinomas were characterized by staining and immunohistological technique, and a few electronmicroscopically. Two types of differentiation could be distinguished. The symptomatology of the three carcinoma patients was complex. Two of these patients suffered from severe ulcer disease reminiscent of Zollinger-Ellison syndrome. The third patient fell ill with erythema and other symptoms known from the \"glucagonoma syndrome\". These malignant tumors could only be incompletely characterized by staining, immunohistology and electronmicroscopy.", "contents": "[Pancreatic island cell tumors and their syndromes. I. Insulinomas, organic hypertinsulinism]. Based on a retrospective investigation of 61 surgical and autopsy specimens, the histopathologic features and clinical manifestations of islet cell tumors are described. In 33 cases reviewed in the first part of this study there existed indications of primary hyperinsulinism (HI) which was generally verified through fast test, stimulation tests or by insulin determination. In 25 cases the HI was caused by benign B-cell adenomas and in 3 cases by metastasizing carcinomas. In another case, polymacronesia of the pancreas with all patterns from abnormally structured islets to true adenomas was found. This patient was free of symptoms after subtotal pancreatectomy. In 4 other cases neither adenomas nor evident islet changes were identified; subtotal pancreatectomy cured only one patient. The insulinomas were surgically removed in 16 cases locally and in 9 cases by partial pancreatectomy. In two patients the adenomas were detected only after a second operation, and a third suffered from HI despite removal of two adenomas. The majority of insulinomas were characterized by staining and immunohistological technique, and a few electronmicroscopically. Two types of differentiation could be distinguished. The symptomatology of the three carcinoma patients was complex. Two of these patients suffered from severe ulcer disease reminiscent of Zollinger-Ellison syndrome. The third patient fell ill with erythema and other symptoms known from the \"glucagonoma syndrome\". These malignant tumors could only be incompletely characterized by staining, immunohistology and electronmicroscopy."}
{"id": "PMID:194306", "title": "[The problem of surgical therapy of malignant kidney tumors].", "content": "Critical examination of the results of surgical treatment and new surgical techniques have produced changes in the operative treatment of hypernephroid kidney cancer and nephroblastoma. The limits to operative treatment are, first, the local extension and infiltration of the tumor and, second, the grade and degree of metastases. Surgical removal of the hypernephroma seems to have a positive effect on metastasis regression only in the case of bone metastases. Nephrectomy is indicated only in cases with solitary metastases which can be removed at a second operation. The possibility of arterial embolization in renal hemorrhage in inoperable patients is demonstrated. Current aspects of the operative treatment of nephroblastoma are discussed.", "contents": "[The problem of surgical therapy of malignant kidney tumors]. Critical examination of the results of surgical treatment and new surgical techniques have produced changes in the operative treatment of hypernephroid kidney cancer and nephroblastoma. The limits to operative treatment are, first, the local extension and infiltration of the tumor and, second, the grade and degree of metastases. Surgical removal of the hypernephroma seems to have a positive effect on metastasis regression only in the case of bone metastases. Nephrectomy is indicated only in cases with solitary metastases which can be removed at a second operation. The possibility of arterial embolization in renal hemorrhage in inoperable patients is demonstrated. Current aspects of the operative treatment of nephroblastoma are discussed."}
{"id": "PMID:194307", "title": "[Herpes simplex encephalitis. A case report with support of the diagnosis by means of brain biopsy].", "content": "The pathogenesis, differential diagnosis and therapeutic problems of herpes simplex encephalitis are discussed. Early diagosis of herpes simplex as a leading, and possibly the sole, cause of acute necrotizing encephalitis is crucial to effective management. Decompressive craniotomy in the presence of fulminating cerebral swelling associated with acute onset of the disease is of value as an adjuvant to definitive therapy with antiviral agents.", "contents": "[Herpes simplex encephalitis. A case report with support of the diagnosis by means of brain biopsy]. The pathogenesis, differential diagnosis and therapeutic problems of herpes simplex encephalitis are discussed. Early diagosis of herpes simplex as a leading, and possibly the sole, cause of acute necrotizing encephalitis is crucial to effective management. Decompressive craniotomy in the presence of fulminating cerebral swelling associated with acute onset of the disease is of value as an adjuvant to definitive therapy with antiviral agents."}
{"id": "PMID:194308", "title": "[Daily excretion of antidiuretic hormone in bronchial carcinoma].", "content": "Daily arginine-vasopressin (AVP) excretion was determined by radioimmunoassay in 60 consecutive cases of untreated lung carcinoma. Control excretion was 61 +/- 34 (SD) in 41 healthy subjects and 50 +/- 38 ng/24 h in 10 patients with chronic lung diseases. Overall 20 out of the 60 cases of lung carcinoma presented with abnormally elevated urinary AVP; In the group with anaplastic oat-cell carcinoma, 15 of 23 had elevated urinary AVP with a mean of 370 +/- 331 (SD) ng/24 h if 2 cases with extremely high values of 11 100 and 55 300 ng/24 h respectively are excluded. None of the 9 patients with large-cell carcinoma had elevated urinary AVP, while only 3 of the 19 cases of epidermoid carcinoma and 2 of the 9 cases of adenocarcinoma had high urinary AVP, with means of 127 +/- 8 and 125 +/- 12 ng/24 h respectively. Plasma osmolality and sodium correlated inversely with AVP excretion. However, only 10 of 23 patients with increased urinary AVP had decreased plasma sodium, although one became hyponatremic 9 weeks later. In one patient AVP excretion normalized after radiotherapy. Plasma renin activity and urinary aldosterone were usually low when urinary AVP was high. Two cases with elevated plasma luteotrophic hormone and another with elevated plasma ACTH, all three presenting with oat-cell carcinoma, were found;", "contents": "[Daily excretion of antidiuretic hormone in bronchial carcinoma]. Daily arginine-vasopressin (AVP) excretion was determined by radioimmunoassay in 60 consecutive cases of untreated lung carcinoma. Control excretion was 61 +/- 34 (SD) in 41 healthy subjects and 50 +/- 38 ng/24 h in 10 patients with chronic lung diseases. Overall 20 out of the 60 cases of lung carcinoma presented with abnormally elevated urinary AVP; In the group with anaplastic oat-cell carcinoma, 15 of 23 had elevated urinary AVP with a mean of 370 +/- 331 (SD) ng/24 h if 2 cases with extremely high values of 11 100 and 55 300 ng/24 h respectively are excluded. None of the 9 patients with large-cell carcinoma had elevated urinary AVP, while only 3 of the 19 cases of epidermoid carcinoma and 2 of the 9 cases of adenocarcinoma had high urinary AVP, with means of 127 +/- 8 and 125 +/- 12 ng/24 h respectively. Plasma osmolality and sodium correlated inversely with AVP excretion. However, only 10 of 23 patients with increased urinary AVP had decreased plasma sodium, although one became hyponatremic 9 weeks later. In one patient AVP excretion normalized after radiotherapy. Plasma renin activity and urinary aldosterone were usually low when urinary AVP was high. Two cases with elevated plasma luteotrophic hormone and another with elevated plasma ACTH, all three presenting with oat-cell carcinoma, were found;"}
{"id": "PMID:194310", "title": "Feline oncornavirus-associated cell membrane antigen: expression in transformed nonproducer mink cells.", "content": "The feline oncornavirus-associated cell membrane antigen (FOCMA) is a target for naturally occurring immunity that protects the cat against development of fibrosarcoma and leukemia. Feline sarcoma virus-transformed \"nonproducer\" mink cells express high levels of FOCMA, but not the major viral structural proteins. Transformation of the same cells by murine sarcoma virus, or infection with feline leukemia virus, which is nontransforming for epithelial or fibroblastic cells, did not induce FOCMA. Thus, FOCMA expression in mind lung cells is specifically associated with transformation by feline sarcoma virus.", "contents": "Feline oncornavirus-associated cell membrane antigen: expression in transformed nonproducer mink cells. The feline oncornavirus-associated cell membrane antigen (FOCMA) is a target for naturally occurring immunity that protects the cat against development of fibrosarcoma and leukemia. Feline sarcoma virus-transformed \"nonproducer\" mink cells express high levels of FOCMA, but not the major viral structural proteins. Transformation of the same cells by murine sarcoma virus, or infection with feline leukemia virus, which is nontransforming for epithelial or fibroblastic cells, did not induce FOCMA. Thus, FOCMA expression in mind lung cells is specifically associated with transformation by feline sarcoma virus."}
{"id": "PMID:194311", "title": "Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophages in culture.", "content": "Dexamethasone and prednisone in physiologic range increased angiotensin converting enzyme 7- to 16-fold in comparison to control in 3 days at maximal stimulation (4 nM steroid) in rabbit alveolar macrophages in culture. The increase was inhibited by actinomycin D (0.1 microng/ml) and 1 micronM cycloheximide, suggesting that de novo transcription and enzyme synthesis are responsible for the increased enzyme activity. This result is evidence for a regulatory mechanism for angiotensin converting enzyme, which is important in blood pressure control.", "contents": "Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophages in culture. Dexamethasone and prednisone in physiologic range increased angiotensin converting enzyme 7- to 16-fold in comparison to control in 3 days at maximal stimulation (4 nM steroid) in rabbit alveolar macrophages in culture. The increase was inhibited by actinomycin D (0.1 microng/ml) and 1 micronM cycloheximide, suggesting that de novo transcription and enzyme synthesis are responsible for the increased enzyme activity. This result is evidence for a regulatory mechanism for angiotensin converting enzyme, which is important in blood pressure control."}
{"id": "PMID:194312", "title": "Physiological evidence for habenula as major link between forebrain and midbrain raphe.", "content": "The lateral habenula is one of the few forebrain areas that project to the midbrain raphe nuclei. Electrical stimulation of the habenula markedly suppressed serotonergic neurons in the midbrain raphe. The suppression was blocked by systemic or microiontophoretic administration of picrotoxin, which suggests that gamma-aminobutyric acid is the inhibitory transmitter in the habenula-raphe pathway. These results support the concept that the habenula may serve a pivotal role in funneling information from the forebrain to the midbrain raphe.", "contents": "Physiological evidence for habenula as major link between forebrain and midbrain raphe. The lateral habenula is one of the few forebrain areas that project to the midbrain raphe nuclei. Electrical stimulation of the habenula markedly suppressed serotonergic neurons in the midbrain raphe. The suppression was blocked by systemic or microiontophoretic administration of picrotoxin, which suggests that gamma-aminobutyric acid is the inhibitory transmitter in the habenula-raphe pathway. These results support the concept that the habenula may serve a pivotal role in funneling information from the forebrain to the midbrain raphe."}
{"id": "PMID:194313", "title": "Circadian rhythm of synaptic excitability in rat and monkey central nervous system.", "content": "Synaptic responses in hippocampal granule cells to stimulation of their afferent fibers from the entorhinal cortex fluctuate with a 24-hour period. The phase of this cycle for rats and monkeys depends on whether the animal is naturally nocturnal or diurnal. In a rat blinded by enucleation, the rhythm persists but drifts out of phase with the rhythm of sighted controls.", "contents": "Circadian rhythm of synaptic excitability in rat and monkey central nervous system. Synaptic responses in hippocampal granule cells to stimulation of their afferent fibers from the entorhinal cortex fluctuate with a 24-hour period. The phase of this cycle for rats and monkeys depends on whether the animal is naturally nocturnal or diurnal. In a rat blinded by enucleation, the rhythm persists but drifts out of phase with the rhythm of sighted controls."}
{"id": "PMID:194314", "title": "[Coagulation and acute disseminated lupus erythematosus. Apropos of 25 cases].", "content": "It is important to study coagulation during lupus disease, not only to detect circulating anticoagulants, which may be the cause of hemorrhage, but also in order to seek chronic hypercoagulability, which is more dangerous as it may favour the development of thrombosis on inflammatory arteritis or aggravate the development of glomerular lesions. We have thus explored in this way 25 patients with systemic lupus of which 17 had histologically confirmed renal disease. 25% had hypocoagulability, but 50% had hypercoagulability which justitied treatment with heparin.", "contents": "[Coagulation and acute disseminated lupus erythematosus. Apropos of 25 cases]. It is important to study coagulation during lupus disease, not only to detect circulating anticoagulants, which may be the cause of hemorrhage, but also in order to seek chronic hypercoagulability, which is more dangerous as it may favour the development of thrombosis on inflammatory arteritis or aggravate the development of glomerular lesions. We have thus explored in this way 25 patients with systemic lupus of which 17 had histologically confirmed renal disease. 25% had hypocoagulability, but 50% had hypercoagulability which justitied treatment with heparin."}
{"id": "PMID:194315", "title": "[Auriculo-ventricular perforation in bacterial endocarditis. Surgical treatment].", "content": "The authors report a case of bacterial endocarditis during which the precise nature of the heart lesions were only discovered at operation. There left ventricle and right atrium. The characteristics of the systolic murmur and the findings on phonocardiography together with left ventricular angiography had suggested mitral incompetence. There were no conduction disorders in this patient which might have helped in preoperative diagnosis. In connection with this case, the authors recall the characteristics of aneuryms of the membranous septum and congenital or acquired communications between the left venticle and the right atrium.", "contents": "[Auriculo-ventricular perforation in bacterial endocarditis. Surgical treatment]. The authors report a case of bacterial endocarditis during which the precise nature of the heart lesions were only discovered at operation. There left ventricle and right atrium. The characteristics of the systolic murmur and the findings on phonocardiography together with left ventricular angiography had suggested mitral incompetence. There were no conduction disorders in this patient which might have helped in preoperative diagnosis. In connection with this case, the authors recall the characteristics of aneuryms of the membranous septum and congenital or acquired communications between the left venticle and the right atrium."}
{"id": "PMID:194319", "title": "[Variation in serum nonesterified fatty acids during glucose tolerance test in undernourished patients with anorexia nervosa and in obese patients].", "content": "Intravenous glucose tolerance tests (0,33 g glucose per kg body weight) are performed in 11 self starved women suffering from anorexia nervosa, 10 obese and 8 normal women. They have no genetic or chemical diabetes and belong to the same age group. Plasma concentrations of immuno-reactive insuline (IRI) and non esterified fatty acids (NEFA) are determined during these tests. The basal concentrations of NEFA are very high in the obese patients. In the starved women the elevation of the basal plasma NEFA concentration is less striking and statistically not significant. The plasma level of NEFA is reduced in all subjects by hyperinsulinism secondary to hyperglycemia. This drop in NEFA concentration is significantly reduced in the obese patients and markedly inhibited in the starved women. This observation points toward an increased resistance to the antilipolytic action of insulin in anorexia nervosa because, in these patients, the glucose load determines a normal increase in plasma IRI but the fall in plasma NEFA concentration is severely impaired.", "contents": "[Variation in serum nonesterified fatty acids during glucose tolerance test in undernourished patients with anorexia nervosa and in obese patients]. Intravenous glucose tolerance tests (0,33 g glucose per kg body weight) are performed in 11 self starved women suffering from anorexia nervosa, 10 obese and 8 normal women. They have no genetic or chemical diabetes and belong to the same age group. Plasma concentrations of immuno-reactive insuline (IRI) and non esterified fatty acids (NEFA) are determined during these tests. The basal concentrations of NEFA are very high in the obese patients. In the starved women the elevation of the basal plasma NEFA concentration is less striking and statistically not significant. The plasma level of NEFA is reduced in all subjects by hyperinsulinism secondary to hyperglycemia. This drop in NEFA concentration is significantly reduced in the obese patients and markedly inhibited in the starved women. This observation points toward an increased resistance to the antilipolytic action of insulin in anorexia nervosa because, in these patients, the glucose load determines a normal increase in plasma IRI but the fall in plasma NEFA concentration is severely impaired."}
{"id": "PMID:194320", "title": "[Angiofollicular lymphoid hyperplasia (Castelman's tumor) in the mediastinum. Apropos of 2 cases].", "content": "The authors report two new cases of angiofollicular hyperplasia of the mediastinum (Castelman's tumour). The only clinical peculiarity was a rapid increase in volume. The authors then review about 200 published cases. Emphasising the existence of 3 different histological types (plasma cell form, vascular hyaline form and intermediate form) and on the association in certain cases of hematological disorders such as anemia and hypergamma globulinemia. The significance of this lesion is discussed. An inflammatory theory with reactional hyperplasia of the beta-lymphocytes is proposed. It was supported by a direct immunofluorescent study of two cases (first study of this type carried out on such lesions) which showed polyclonal plasma cell hyperplasia predominating on the IgG.", "contents": "[Angiofollicular lymphoid hyperplasia (Castelman's tumor) in the mediastinum. Apropos of 2 cases]. The authors report two new cases of angiofollicular hyperplasia of the mediastinum (Castelman's tumour). The only clinical peculiarity was a rapid increase in volume. The authors then review about 200 published cases. Emphasising the existence of 3 different histological types (plasma cell form, vascular hyaline form and intermediate form) and on the association in certain cases of hematological disorders such as anemia and hypergamma globulinemia. The significance of this lesion is discussed. An inflammatory theory with reactional hyperplasia of the beta-lymphocytes is proposed. It was supported by a direct immunofluorescent study of two cases (first study of this type carried out on such lesions) which showed polyclonal plasma cell hyperplasia predominating on the IgG."}
{"id": "PMID:194321", "title": "[Inappropriate secretion of antidiuretic hormone: true and false Schwartz-Bartter syndrome. Apropos of 2 cases].", "content": "The authors report two cases and consider the various physiopathological mechanisms of inappropriate hypersecretion of antidiuretic hormone. An exploration including clearance of free water and, in some cases, estimation of ADH before and after a water load, then before and after administration of ethyl alcohol, permits one to determine the mechanism. It seems advisable to reserve the term Schwartz-Bartter syndrome to paraneoplasic syndromes linked to ectopic and autonomous secretion of ADH.", "contents": "[Inappropriate secretion of antidiuretic hormone: true and false Schwartz-Bartter syndrome. Apropos of 2 cases]. The authors report two cases and consider the various physiopathological mechanisms of inappropriate hypersecretion of antidiuretic hormone. An exploration including clearance of free water and, in some cases, estimation of ADH before and after a water load, then before and after administration of ethyl alcohol, permits one to determine the mechanism. It seems advisable to reserve the term Schwartz-Bartter syndrome to paraneoplasic syndromes linked to ectopic and autonomous secretion of ADH."}
{"id": "PMID:194322", "title": "[Anemia in chronic lead poisoning. Apropos of 2 cases].", "content": "The authors report two cases of lead poisoning in which the diagnosis was made following anemia. They recall the clinical, laboratory and physiopathological characteristics of the blood signs of chronic lead poisoning. Anemia is the result of more rapid aging of the red cells, and of the effect of lead on erythropoiesis. The diagnosis is based on the finding of stippled red cells, on the rise in urinary delta-levulinic acid and on urinary lead after chelation.", "contents": "[Anemia in chronic lead poisoning. Apropos of 2 cases]. The authors report two cases of lead poisoning in which the diagnosis was made following anemia. They recall the clinical, laboratory and physiopathological characteristics of the blood signs of chronic lead poisoning. Anemia is the result of more rapid aging of the red cells, and of the effect of lead on erythropoiesis. The diagnosis is based on the finding of stippled red cells, on the rise in urinary delta-levulinic acid and on urinary lead after chelation."}
{"id": "PMID:194323", "title": "[Chronic atrophying polychrondritis].", "content": "After the description of the clinical signs (chondritis, arthritis, eye signs, cardiovascular signs) and laboratory signs of chronic atrophying polychrondritis, the authors study its pathology and the electron microscope findings, its diagnosis and the most recently proposed criteria, its course and therapeutic difficulties, its classification and finally discuss recent biochemical and immunologic data and the pathogenesis.", "contents": "[Chronic atrophying polychrondritis]. After the description of the clinical signs (chondritis, arthritis, eye signs, cardiovascular signs) and laboratory signs of chronic atrophying polychrondritis, the authors study its pathology and the electron microscope findings, its diagnosis and the most recently proposed criteria, its course and therapeutic difficulties, its classification and finally discuss recent biochemical and immunologic data and the pathogenesis."}
{"id": "PMID:194329", "title": "[Cutaneous manifestations in trisomy 21].", "content": "The possibility of cutaneous manifestations in Down's syndromes not a surprise because we known that this affection affects the three embryonic parts. This cutaneous disorder is described by many authors but it is variable and not specific. The authors had occasion to see four cases of alopecia areata in mongolian children. They do an analytic study of variable manifestations. They insist on frequency of hyperkeratotic lesions, alopecia areata, alterations of vasomotricity and elastic dystrophies. In the group of chromosomic aberrations, down's syndrome is alone where the cutaneous manifestations are studied because the patients have a good survival.", "contents": "[Cutaneous manifestations in trisomy 21]. The possibility of cutaneous manifestations in Down's syndromes not a surprise because we known that this affection affects the three embryonic parts. This cutaneous disorder is described by many authors but it is variable and not specific. The authors had occasion to see four cases of alopecia areata in mongolian children. They do an analytic study of variable manifestations. They insist on frequency of hyperkeratotic lesions, alopecia areata, alterations of vasomotricity and elastic dystrophies. In the group of chromosomic aberrations, down's syndrome is alone where the cutaneous manifestations are studied because the patients have a good survival."}
{"id": "PMID:194330", "title": "[Tuberculosis of migrant black Africans].", "content": "A study of 357 cases of tuberculosis in African negro immigrants seen between 1967 and 1971 showed the predominance of respiratory lesions especially pulmonary and/or hilar ganglio-mediastinal lesions compared with lesions elsewhere, e.g. lymph nodes, bones, joints, pericardium, peritoneum, livers, and the frequency of multiple lesions. Routine detection should be more frequent in high risk subjects, who are almost always allergic on arrival in France. In spite of frequent resistance, above all primary, treatment gave good results in 83% of cases. In future, we will have to take into consideration the possibility of relapses and perhaps more numerous resistances, including to rifamycin and ethambutol.", "contents": "[Tuberculosis of migrant black Africans]. A study of 357 cases of tuberculosis in African negro immigrants seen between 1967 and 1971 showed the predominance of respiratory lesions especially pulmonary and/or hilar ganglio-mediastinal lesions compared with lesions elsewhere, e.g. lymph nodes, bones, joints, pericardium, peritoneum, livers, and the frequency of multiple lesions. Routine detection should be more frequent in high risk subjects, who are almost always allergic on arrival in France. In spite of frequent resistance, above all primary, treatment gave good results in 83% of cases. In future, we will have to take into consideration the possibility of relapses and perhaps more numerous resistances, including to rifamycin and ethambutol."}
{"id": "PMID:194331", "title": "[Hyperlipemias and their manifestations in the rheumatological sphere].", "content": "It is fairly frequent to encounter hyperlipemia on a rheumatic unit. Firstly the symptoms of certain idiopathic hyperlipemias sometimes include rheumatic changes. The latter include firstly, arthritis and tendinitis, above all observed in Type II hyperlipoproteinemia but also mentionned in Type IV, and secondly, exceptional bony lesions (generally of xanthoma type) which seem to occur exclusively in severe hyperglyceridemia. A few bone and joint diseases, such as gout or aseptic necrosis, frequently coexist with dyslipemia. Furthermore, various diseases may be simultaneously responsible for secondary hyperlipemia and involvement of the locomotor apparatus. Finally, the iatrogenic manifestations of the locomotor system appear mainly due to hypolipemic drugs, e.g. the muscle disorders seen in a few patients treated with clofibrate.", "contents": "[Hyperlipemias and their manifestations in the rheumatological sphere]. It is fairly frequent to encounter hyperlipemia on a rheumatic unit. Firstly the symptoms of certain idiopathic hyperlipemias sometimes include rheumatic changes. The latter include firstly, arthritis and tendinitis, above all observed in Type II hyperlipoproteinemia but also mentionned in Type IV, and secondly, exceptional bony lesions (generally of xanthoma type) which seem to occur exclusively in severe hyperglyceridemia. A few bone and joint diseases, such as gout or aseptic necrosis, frequently coexist with dyslipemia. Furthermore, various diseases may be simultaneously responsible for secondary hyperlipemia and involvement of the locomotor apparatus. Finally, the iatrogenic manifestations of the locomotor system appear mainly due to hypolipemic drugs, e.g. the muscle disorders seen in a few patients treated with clofibrate."}
{"id": "PMID:194332", "title": "[Treatment of the syndrome of inappropriate secretion of antidiuretic hormone with demethylchlortetracycline. Apropos of 2 cases].", "content": "Two cases of inappropriate antidiuresis are reported, one associated with small cell anaplastic bronchial carcinoma, the other secondary to acute hydrocephalus. ttreatment with demethylchlortetracycline proved effective in both cases. Treatment of the inappropriate antidiuretic syndrome is discussed and the advantages of demethylchlortetracycline emphasised. This antibiotic seems to represent the treatment of choice of the chronic syndrome of inappropriate antidiuresis.", "contents": "[Treatment of the syndrome of inappropriate secretion of antidiuretic hormone with demethylchlortetracycline. Apropos of 2 cases]. Two cases of inappropriate antidiuresis are reported, one associated with small cell anaplastic bronchial carcinoma, the other secondary to acute hydrocephalus. ttreatment with demethylchlortetracycline proved effective in both cases. Treatment of the inappropriate antidiuretic syndrome is discussed and the advantages of demethylchlortetracycline emphasised. This antibiotic seems to represent the treatment of choice of the chronic syndrome of inappropriate antidiuresis."}
{"id": "PMID:194333", "title": "[Intestinal bacterial flora in patients with colopathies. Study of samples obtained by colonoscopy].", "content": "This enquiry, the limits of which are easy to determine, permits one to note that in patients with chronic hemorrhagic colonic disease samples of digestive juice, carried, out at the level of the colonic mucosa, permit isolation of a large number of pseudomonadaceae, these bacteria are extremely various. A single patient may harbour 10 to 12 species. These bacteria, usually harmless, belong to the natural microbiocenoses, but they may under certain circumstances, increase in number and, according to Fabiani, induce severe symptoms or even be fatal. The mass of bacteria isolated and identified did not permit a study of bacterial sensitivity. The most seriously affected subjects clinically, usually had various bacteria which excludes the accusation of one species and eliminates any idea of bacterial specificity in the constitution of the syndromes observed. The disturbance seems to be a consequence of these chronic diseases and not the cause. In fact, no pathogenic germ was isolated, which one might consider to be responsible for the disease. Finally, it is wise to conclude that patients with irritable colon syndromes who formed part of this investigation, simply presented some imbalance in the bacterial flora which was sometimes very marked with a predominance of proteolytic Pseudomonas.", "contents": "[Intestinal bacterial flora in patients with colopathies. Study of samples obtained by colonoscopy]. This enquiry, the limits of which are easy to determine, permits one to note that in patients with chronic hemorrhagic colonic disease samples of digestive juice, carried, out at the level of the colonic mucosa, permit isolation of a large number of pseudomonadaceae, these bacteria are extremely various. A single patient may harbour 10 to 12 species. These bacteria, usually harmless, belong to the natural microbiocenoses, but they may under certain circumstances, increase in number and, according to Fabiani, induce severe symptoms or even be fatal. The mass of bacteria isolated and identified did not permit a study of bacterial sensitivity. The most seriously affected subjects clinically, usually had various bacteria which excludes the accusation of one species and eliminates any idea of bacterial specificity in the constitution of the syndromes observed. The disturbance seems to be a consequence of these chronic diseases and not the cause. In fact, no pathogenic germ was isolated, which one might consider to be responsible for the disease. Finally, it is wise to conclude that patients with irritable colon syndromes who formed part of this investigation, simply presented some imbalance in the bacterial flora which was sometimes very marked with a predominance of proteolytic Pseudomonas."}
{"id": "PMID:194334", "title": "[Polyradiculoneuritis in visceral cancer. Review of the literature. Apropos of 2 cases].", "content": "One should distinguish two types of polyradiculoneuritis during visceral carcinoma. Metastic polyneuritis and paraneoplastic polyneuritis. They fulfil distinct anatomical criteria and their pathogenesis is different. Both, however, have clinical analogies and a similar course. The survival time in both types is usually a few weeks. It rarely exceeds one year.", "contents": "[Polyradiculoneuritis in visceral cancer. Review of the literature. Apropos of 2 cases]. One should distinguish two types of polyradiculoneuritis during visceral carcinoma. Metastic polyneuritis and paraneoplastic polyneuritis. They fulfil distinct anatomical criteria and their pathogenesis is different. Both, however, have clinical analogies and a similar course. The survival time in both types is usually a few weeks. It rarely exceeds one year."}
{"id": "PMID:194342", "title": "A mastoid osteoma causing intracranial complications. A case report.", "content": "A case report of a mastoid sinus osteoma with intracranial complications is presented. This is the first report of a mastoid osteoma causing intracranial complications. The tumour is one of the paranasal osteoma group. It produced displacement and compression of the posterior fossa structures. The patient was operated on by means of a combined intra- and extradural approach.", "contents": "A mastoid osteoma causing intracranial complications. A case report. A case report of a mastoid sinus osteoma with intracranial complications is presented. This is the first report of a mastoid osteoma causing intracranial complications. The tumour is one of the paranasal osteoma group. It produced displacement and compression of the posterior fossa structures. The patient was operated on by means of a combined intra- and extradural approach."}
{"id": "PMID:194345", "title": "Reactivation of chick erythrocyte nuclei after fusion with enucleated cells.", "content": "Inactivated Sendai virus was used to fuse nucleated chick erythrocytes with mouse L and A9 cells which had been enucleated by centrifugation in the presence of cytochalasinB. The enucleation step removed the nuclei from more than 99% of the cells. During the fusion step, chick erythrocyte nuclei were introduced into 20% of the enucleated mouse cytoplasms. This resulted in the formation of a large number of \"reconstituted cells\" where practically all the cytoplasm originated from the mouse cell while the nucleus was of chick origin. The chick erythrocyte nuclei appeared to become well integrated into the mouse cytoplasms since they increased dramatically in size and dry mass, formed nucleolus-like bodies, and resumed RNA synthesis. This, however, did not prevent a gradual decrease in the rate of protein synthesis in the cytoplasm after the removal of the mouse nucleus. Protein synthesis decayed at a similar rate in both reconstituted and enucleated cells. The majority of these \"cells\" died within 48 h and all of them within 5 days after enucleation/fusion. By contrast, the small number of L cells which failed to become enucleated multiplied rapidly. The results obtained suggest that the reactivation of the chick erythrocyte nuclei is not fast enough to rescue the enucleated mouse cytoplasms.", "contents": "Reactivation of chick erythrocyte nuclei after fusion with enucleated cells. Inactivated Sendai virus was used to fuse nucleated chick erythrocytes with mouse L and A9 cells which had been enucleated by centrifugation in the presence of cytochalasinB. The enucleation step removed the nuclei from more than 99% of the cells. During the fusion step, chick erythrocyte nuclei were introduced into 20% of the enucleated mouse cytoplasms. This resulted in the formation of a large number of \"reconstituted cells\" where practically all the cytoplasm originated from the mouse cell while the nucleus was of chick origin. The chick erythrocyte nuclei appeared to become well integrated into the mouse cytoplasms since they increased dramatically in size and dry mass, formed nucleolus-like bodies, and resumed RNA synthesis. This, however, did not prevent a gradual decrease in the rate of protein synthesis in the cytoplasm after the removal of the mouse nucleus. Protein synthesis decayed at a similar rate in both reconstituted and enucleated cells. The majority of these \"cells\" died within 48 h and all of them within 5 days after enucleation/fusion. By contrast, the small number of L cells which failed to become enucleated multiplied rapidly. The results obtained suggest that the reactivation of the chick erythrocyte nuclei is not fast enough to rescue the enucleated mouse cytoplasms."}
{"id": "PMID:194346", "title": "Control of the expression of a herpes simplex virus thymidine kinase gene incorporated into thymidine kinase-deficient mouse cells.", "content": "When thymidine kinase-deficient mouse cells \"transformed\" by in activated herpes simplex virus and expressing the viral thymidine kinase (TK) are grown in nonselective medium, there is an exponential decay in the proportion of cells that continue to express the viral enzyme. However, the viral TK can be reactivated at a frequency of approximately 1 cell in 10(6) in every population that has lost TK activity. When cells in which the viral TK has been reactivated are grown in nonselective medium, a decay in the expression of the viral enzyme occurs again at the same rate as in the initial transformed population. Studies on the reactivation of viral TK indicate that reappearance of the enzyme is not induced by the selective medium (HAT) used to detect cells in which the enzyme has reappeared. Furthermore, treatments known to induce latent viruses in other systems--eg, exposure of the cells to mutagens or cell fusion--do not affect the frequency with which viral TK is reactivated.", "contents": "Control of the expression of a herpes simplex virus thymidine kinase gene incorporated into thymidine kinase-deficient mouse cells. When thymidine kinase-deficient mouse cells \"transformed\" by in activated herpes simplex virus and expressing the viral thymidine kinase (TK) are grown in nonselective medium, there is an exponential decay in the proportion of cells that continue to express the viral enzyme. However, the viral TK can be reactivated at a frequency of approximately 1 cell in 10(6) in every population that has lost TK activity. When cells in which the viral TK has been reactivated are grown in nonselective medium, a decay in the expression of the viral enzyme occurs again at the same rate as in the initial transformed population. Studies on the reactivation of viral TK indicate that reappearance of the enzyme is not induced by the selective medium (HAT) used to detect cells in which the enzyme has reappeared. Furthermore, treatments known to induce latent viruses in other systems--eg, exposure of the cells to mutagens or cell fusion--do not affect the frequency with which viral TK is reactivated."}
{"id": "PMID:194347", "title": "The dose-response relationship for ethyl methanesulfonate-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells.", "content": "The frequency of ethyl methanesulfonate (EMS)-induced mutations to 6-thioguanine resistance in a Chinese hamster ovary cells clone K1-BH4 was studied at many EMS doses including the minimally lethal range (0-100 microng/ml) as well as the exponential killing portion (100-800 microng/ml) of the survival curve. The mutation frequency increases approximately in proportion with increasing EMS concentration at a fixed treatment time. The pooled data for the observed mutation frequency, f(X), as a function of EMS dose X, is adequately described by a linear function f(X)=10(-6)(8.73+3.45 X), where 0 less than or equal to X less than or equal to 800 microng/ml. One interpretation of the linear dose-response is that, as a result of EMS treatment, ethylation of cellular constituents occurs, which is directly responsible for the mutation. Biochemical analyses demonstrate that most of the randomly isolated 6-thioguanine-resistant variants possess a highly reduced or undetectable level of HGPRT activity suggesting that the EMS-induced mutations to 6-thioguanine resistance affect primarily, if not exclusively, the HGPRT locus.", "contents": "The dose-response relationship for ethyl methanesulfonate-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells. The frequency of ethyl methanesulfonate (EMS)-induced mutations to 6-thioguanine resistance in a Chinese hamster ovary cells clone K1-BH4 was studied at many EMS doses including the minimally lethal range (0-100 microng/ml) as well as the exponential killing portion (100-800 microng/ml) of the survival curve. The mutation frequency increases approximately in proportion with increasing EMS concentration at a fixed treatment time. The pooled data for the observed mutation frequency, f(X), as a function of EMS dose X, is adequately described by a linear function f(X)=10(-6)(8.73+3.45 X), where 0 less than or equal to X less than or equal to 800 microng/ml. One interpretation of the linear dose-response is that, as a result of EMS treatment, ethylation of cellular constituents occurs, which is directly responsible for the mutation. Biochemical analyses demonstrate that most of the randomly isolated 6-thioguanine-resistant variants possess a highly reduced or undetectable level of HGPRT activity suggesting that the EMS-induced mutations to 6-thioguanine resistance affect primarily, if not exclusively, the HGPRT locus."}
{"id": "PMID:194344", "title": "Simultaneous isolation of herpesvirus hominis type 2 and cytomegalovirus from the genital tract of a woman.", "content": "Herpesvirus hominis and cytomegalovirus are closely related deoxyribonucleic acid viruses which have been isolated from the genital tract. This report describes the simultaneous isolation of Herpesvirus hominis type 2 and cytomegalovirus from the genital tract of a woman preceded by the isolation of cytomegalovirus from the semen and a probable herpetic penile infection in her sexual partner.", "contents": "Simultaneous isolation of herpesvirus hominis type 2 and cytomegalovirus from the genital tract of a woman. Herpesvirus hominis and cytomegalovirus are closely related deoxyribonucleic acid viruses which have been isolated from the genital tract. This report describes the simultaneous isolation of Herpesvirus hominis type 2 and cytomegalovirus from the genital tract of a woman preceded by the isolation of cytomegalovirus from the semen and a probable herpetic penile infection in her sexual partner."}
{"id": "PMID:194348", "title": "Heterotopic chondrogenesis and osteogenesis induced by transformed cells: use of nude mice as a model system.", "content": "A subline of HeLa cells was shown to induce cartilage and bone formation in congenitally athymic (nude) mice when injected intramuscularly. The chondrogenesis and osteogenesis observed was similar to that found when other inducing epithelia are injected intramuscularly into cortisone-treated mice. A tumorigenic SV40 T antigen-positive human-mouse somatic cell hybrid with human chromosomes C7 and C6 did not induce cartilage or bone formation under similar conditions. The nude mouse may thus provide a system in which to investigate experimental host-cell differentiation without the complications of immunosuppression.", "contents": "Heterotopic chondrogenesis and osteogenesis induced by transformed cells: use of nude mice as a model system. A subline of HeLa cells was shown to induce cartilage and bone formation in congenitally athymic (nude) mice when injected intramuscularly. The chondrogenesis and osteogenesis observed was similar to that found when other inducing epithelia are injected intramuscularly into cortisone-treated mice. A tumorigenic SV40 T antigen-positive human-mouse somatic cell hybrid with human chromosomes C7 and C6 did not induce cartilage or bone formation under similar conditions. The nude mouse may thus provide a system in which to investigate experimental host-cell differentiation without the complications of immunosuppression."}
{"id": "PMID:194350", "title": "Intrathoracic chemodectoma with multiple localisations.", "content": "In 1958 a mediastinal tumour was discovered in an asymptomatic woman with a history of vomiting and an oesophageal anomaly which had not been treated. A tumour of the anterosuperior mediastinum in relation to the aortic arch was extirpated and proved to be a chemodectoma or non-chromaffin paraganglioma. At subsequent follow-ups the mediastinum was never normal and the heart size progressively increased, the oesophageal anomaly remaining unchanged. A small opacity appeared in the left lung in 1974. An operation performed in 1975 revealed an osteochondroma in the lung, pericarditis, and an intrapericardial chemodectoma. The oesophagus was not explored. An intrathoracic chemodectoma is rare. The importance of angiography in its diagnosis is emphasised. Malignant degeneration is seldom observed. Therapy is surgical, the tumour being radioresistant. The possibility to be considered in our patient was either relapse of the tumour with degeneration or multiple localisations of the tumour.", "contents": "Intrathoracic chemodectoma with multiple localisations. In 1958 a mediastinal tumour was discovered in an asymptomatic woman with a history of vomiting and an oesophageal anomaly which had not been treated. A tumour of the anterosuperior mediastinum in relation to the aortic arch was extirpated and proved to be a chemodectoma or non-chromaffin paraganglioma. At subsequent follow-ups the mediastinum was never normal and the heart size progressively increased, the oesophageal anomaly remaining unchanged. A small opacity appeared in the left lung in 1974. An operation performed in 1975 revealed an osteochondroma in the lung, pericarditis, and an intrapericardial chemodectoma. The oesophagus was not explored. An intrathoracic chemodectoma is rare. The importance of angiography in its diagnosis is emphasised. Malignant degeneration is seldom observed. Therapy is surgical, the tumour being radioresistant. The possibility to be considered in our patient was either relapse of the tumour with degeneration or multiple localisations of the tumour."}
{"id": "PMID:194359", "title": "Acute effects of intravenous infusion of conjugated estrogen on serum levels of LH and FSH in post-menopausal and castrated women.", "content": "In order to quantify the changes of feed-back effect of estrogen on the release of pituitary gonadotropin which is regulated by the hypothalamic-pituitary-ovarian system, the responses of LH and FSH to the intravenous infusion of 20 mg of conjugated estrogen were studied in 49 post-menopausal and 20 castrated women. In the group of women within 1 year after menopause, serum LH levels were elevated following the infusion of the conjugated estrogen. The responses of serum LH and FSH levels were different between post-menopausal and castrated women. The data indicated that the difference between the two groups was probably due to the difference of secrection patterns of the gonadotropins in post-menopausal and castrated women.", "contents": "Acute effects of intravenous infusion of conjugated estrogen on serum levels of LH and FSH in post-menopausal and castrated women. In order to quantify the changes of feed-back effect of estrogen on the release of pituitary gonadotropin which is regulated by the hypothalamic-pituitary-ovarian system, the responses of LH and FSH to the intravenous infusion of 20 mg of conjugated estrogen were studied in 49 post-menopausal and 20 castrated women. In the group of women within 1 year after menopause, serum LH levels were elevated following the infusion of the conjugated estrogen. The responses of serum LH and FSH levels were different between post-menopausal and castrated women. The data indicated that the difference between the two groups was probably due to the difference of secrection patterns of the gonadotropins in post-menopausal and castrated women."}
{"id": "PMID:194360", "title": "A trial of quantitative classification of surgical stress.", "content": "The severity of various surgical stresses was classified quantitatively on the basis of degree of adrenocortical stimulation by ACTH-Z. Urinary 17-OHCS (total, free and individual fractions) were dtermined in sixteen patients who underwent various operations and were injected some doses of ACTH-Z. The following quantitative classification of surgical stress was possible. In the group of ureterolithotomy and pyeloithotomy, the severity of operative stress appeared to be equivalent to the adrenocortical stimulation caused by injection of 0.125 mg to 0.25 mg of ACTH-Z. The severity in the group of ureterotomia externa was nearly the same as that in the above group. In the group of nephrectomy by oblique incision, the severity of stress appeared to correspond to the stimulation by injection of 0.25 mg or more of ACTH-Z. The group of total nephroureterectomy with partial cystectomy showed the severity which would correspond to the degree of stimulation by injection of about 0.5 mg ACTH-Z, and the group of transperitoneal nephrectomy, by injection of 0.25 mg to 0.5 mg of ACTH-Z.", "contents": "A trial of quantitative classification of surgical stress. The severity of various surgical stresses was classified quantitatively on the basis of degree of adrenocortical stimulation by ACTH-Z. Urinary 17-OHCS (total, free and individual fractions) were dtermined in sixteen patients who underwent various operations and were injected some doses of ACTH-Z. The following quantitative classification of surgical stress was possible. In the group of ureterolithotomy and pyeloithotomy, the severity of operative stress appeared to be equivalent to the adrenocortical stimulation caused by injection of 0.125 mg to 0.25 mg of ACTH-Z. The severity in the group of ureterotomia externa was nearly the same as that in the above group. In the group of nephrectomy by oblique incision, the severity of stress appeared to correspond to the stimulation by injection of 0.25 mg or more of ACTH-Z. The group of total nephroureterectomy with partial cystectomy showed the severity which would correspond to the degree of stimulation by injection of about 0.5 mg ACTH-Z, and the group of transperitoneal nephrectomy, by injection of 0.25 mg to 0.5 mg of ACTH-Z."}
{"id": "PMID:194364", "title": "Blood production rates of estrogens in women with differing ratios of urinary estrogen conjugates.", "content": "On the basis of the ratios of the estrogen conjugates in their urine (estriol/estrone + estradiol: E3/[E1+E2]), 19 women were divided into two groups: 9 women had ratios less than 0.6 and 10 women had ratios greater than 1.3. All women had measurements made of endogenous estrogens in their plasma by radioimmunoassay. They were then given constant infusions of 3H-estrone, 3H-estradiol and 14C-estriol during days 5-7 and days 20-22 of their cycles, and metabolic clearance rates (MCR) and blood production rates (PB) of estrone, estradiol and estriol were determined. Despite the wide disparity in their ratios of urinary estrogens, no differences could be found between the groups for the MCR's and PB's for all estrogens at either time of the cycle. The mean ratios of PB's (PB3/[PB2+PB1]) of estrone, estradiol and estriol ranged from 0.07 to 0.10 for each group during the cycle. The amounts of estriol entering the blood are small compared to the amounts of estrone and estradiol and do not correlate with the ratios of their urinary conjugates.", "contents": "Blood production rates of estrogens in women with differing ratios of urinary estrogen conjugates. On the basis of the ratios of the estrogen conjugates in their urine (estriol/estrone + estradiol: E3/[E1+E2]), 19 women were divided into two groups: 9 women had ratios less than 0.6 and 10 women had ratios greater than 1.3. All women had measurements made of endogenous estrogens in their plasma by radioimmunoassay. They were then given constant infusions of 3H-estrone, 3H-estradiol and 14C-estriol during days 5-7 and days 20-22 of their cycles, and metabolic clearance rates (MCR) and blood production rates (PB) of estrone, estradiol and estriol were determined. Despite the wide disparity in their ratios of urinary estrogens, no differences could be found between the groups for the MCR's and PB's for all estrogens at either time of the cycle. The mean ratios of PB's (PB3/[PB2+PB1]) of estrone, estradiol and estriol ranged from 0.07 to 0.10 for each group during the cycle. The amounts of estriol entering the blood are small compared to the amounts of estrone and estradiol and do not correlate with the ratios of their urinary conjugates."}
{"id": "PMID:194366", "title": "Rejectability of virus-induced tumors and nonrejectability of spontaneous tumors: a lesson in contrasts.", "content": "In contrast to the excellent surveillance against tumors induced by the ubiquitous viruses in their natural host species, spontaneous tumors developing naturally, without experimental interference, evoke little or no rejection reaction. This may be viewed in relation to the natural history of tumors. In most cases, tumors evolve in several steps, with a successful of clonal variants following each other, characterized by increasing independence of host regulations (including immune restrictions). This process is commonly designated as tumor progression. In all probability, selection for nonrejectability is part of this process. Selection of the host for rejecting capacity is unlikely to play any major role, since the overwhelming majority of the naturally occurring tumors arise after the host has passed the peak of its reproductive period. The nonrejectability of spontaneous tumors may be overcome by target-cell modification, e.g., by chemical coupling, somatic cell hybridization, or viral xenogenization. Furthermore, genetic analysis of the F1 resistance effect in relation to seemingly nonrejectable tumors may reveal the existence of specific immune-response (Ir) genes that can influence the recognition of tumor-associated membrane changes by the host immune system.", "contents": "Rejectability of virus-induced tumors and nonrejectability of spontaneous tumors: a lesson in contrasts. In contrast to the excellent surveillance against tumors induced by the ubiquitous viruses in their natural host species, spontaneous tumors developing naturally, without experimental interference, evoke little or no rejection reaction. This may be viewed in relation to the natural history of tumors. In most cases, tumors evolve in several steps, with a successful of clonal variants following each other, characterized by increasing independence of host regulations (including immune restrictions). This process is commonly designated as tumor progression. In all probability, selection for nonrejectability is part of this process. Selection of the host for rejecting capacity is unlikely to play any major role, since the overwhelming majority of the naturally occurring tumors arise after the host has passed the peak of its reproductive period. The nonrejectability of spontaneous tumors may be overcome by target-cell modification, e.g., by chemical coupling, somatic cell hybridization, or viral xenogenization. Furthermore, genetic analysis of the F1 resistance effect in relation to seemingly nonrejectable tumors may reveal the existence of specific immune-response (Ir) genes that can influence the recognition of tumor-associated membrane changes by the host immune system."}
{"id": "PMID:194375", "title": "[Effect of ascorbic acid on glucocorticoid metabolism in guinea pigs].", "content": "Ascorbic acid administered for 18-20 days (daily by 100 mg per 1 kg of weight per os) causes redistribution of certain fractions of 17-OCS excreted with urine (a decrease in the content of free F and F/E ratio, an increase in the content of THF, THE and THS, a more frequent appearance of substances). In the blood plasm and adrenals concentration of 11-OCS rises. When determining the available functional reserves of the adrenal cortex under these conditions, an increase in the content of F, E and S unchanged forms is observed in response to ACTH administration as distinct from the initial state. The rise in concentration of 11-OCS in the adrenals and blood plasm is less pronounced than in the control. A conclusion is drawn that ascorbic acid affects metabolism of glucocorticoids and changes the reaction of the adrenaocortical system on the action of ACTH.", "contents": "[Effect of ascorbic acid on glucocorticoid metabolism in guinea pigs]. Ascorbic acid administered for 18-20 days (daily by 100 mg per 1 kg of weight per os) causes redistribution of certain fractions of 17-OCS excreted with urine (a decrease in the content of free F and F/E ratio, an increase in the content of THF, THE and THS, a more frequent appearance of substances). In the blood plasm and adrenals concentration of 11-OCS rises. When determining the available functional reserves of the adrenal cortex under these conditions, an increase in the content of F, E and S unchanged forms is observed in response to ACTH administration as distinct from the initial state. The rise in concentration of 11-OCS in the adrenals and blood plasm is less pronounced than in the control. A conclusion is drawn that ascorbic acid affects metabolism of glucocorticoids and changes the reaction of the adrenaocortical system on the action of ACTH."}
{"id": "PMID:194376", "title": "[Changes in alanine and aspartate aminotransferase activity in rabbit tissues following administration of hydrocortisone and ACTH].", "content": "Hydrocortisone and ACTH administration induced AlT- and AsT-activity changes in the brain hemispheres, liver, spleen, muscles and blood plasm of rabbits. The direction and rate of changes of the studied enzymes activity in the tissues was not the same after hydrocortisone and ACTH injections and depended on duration of the hormones administration. The changes in the AlT-activity were more essential than those in the AsT-activity for all tissues.", "contents": "[Changes in alanine and aspartate aminotransferase activity in rabbit tissues following administration of hydrocortisone and ACTH]. Hydrocortisone and ACTH administration induced AlT- and AsT-activity changes in the brain hemispheres, liver, spleen, muscles and blood plasm of rabbits. The direction and rate of changes of the studied enzymes activity in the tissues was not the same after hydrocortisone and ACTH injections and depended on duration of the hormones administration. The changes in the AlT-activity were more essential than those in the AsT-activity for all tissues."}
{"id": "PMID:194377", "title": "[Adenylate system of rat liver tissue during chemical carcinogenesis].", "content": "The ratio of adenylic nucleotides, activity of adenylatekinase and ATPase were studied in the liver subcellular fractions and in tumours of rats with cancerogenesis induced by diethylnitrozamine and p-dimethylaminoazobenzene. The adenylatekinase activity increases in the liver hyaloplasm of rats with tumours and in the tissue of the tumours themselves, the activity of ATPase is unchanged. An increase in the adenylatekinase activity in hyaloplasm is accompanied by a decrease in the level of ATP with the absence of changes in ADP and AMP, that results in a drop \"of the adenylate energy charge\" value (Atkinson reflecting the balance of adenyl nucleotides in a cell.", "contents": "[Adenylate system of rat liver tissue during chemical carcinogenesis]. The ratio of adenylic nucleotides, activity of adenylatekinase and ATPase were studied in the liver subcellular fractions and in tumours of rats with cancerogenesis induced by diethylnitrozamine and p-dimethylaminoazobenzene. The adenylatekinase activity increases in the liver hyaloplasm of rats with tumours and in the tissue of the tumours themselves, the activity of ATPase is unchanged. An increase in the adenylatekinase activity in hyaloplasm is accompanied by a decrease in the level of ATP with the absence of changes in ADP and AMP, that results in a drop \"of the adenylate energy charge\" value (Atkinson reflecting the balance of adenyl nucleotides in a cell."}
{"id": "PMID:194379", "title": "[Mechanism of calcium ion transport in brain microsome fractions].", "content": "The influence of Ca2+ in rising concentrations on the ATP-dependent Ca2+-binding system of the brain microsome fraction, the inhibitory effect of SH-reagents on it and the protective effect of ATP correlate with the properties of the Mg2+-dependent Ca2+-activated ATPase of this fraction. Such properties of the system as inactivation with an increase in Ca2+-concentration effect of phosphate and oxalate, relation to detergents cannot be explained from the view point of the tri-phosphoinozitid-dependent binding of Ca2+. These data indicate that the general mechanism of Ca2+ transport in the brain microsome fraction is similar to the mechanism of this process in the sarcoplasmatic reticulum and is realized with participation of Mg2+, Ca2+-ATPase.", "contents": "[Mechanism of calcium ion transport in brain microsome fractions]. The influence of Ca2+ in rising concentrations on the ATP-dependent Ca2+-binding system of the brain microsome fraction, the inhibitory effect of SH-reagents on it and the protective effect of ATP correlate with the properties of the Mg2+-dependent Ca2+-activated ATPase of this fraction. Such properties of the system as inactivation with an increase in Ca2+-concentration effect of phosphate and oxalate, relation to detergents cannot be explained from the view point of the tri-phosphoinozitid-dependent binding of Ca2+. These data indicate that the general mechanism of Ca2+ transport in the brain microsome fraction is similar to the mechanism of this process in the sarcoplasmatic reticulum and is realized with participation of Mg2+, Ca2+-ATPase."}
{"id": "PMID:194380", "title": "[Activity of carbohydrate metabolism enzymes in loach embryos under the influence of hormones].", "content": "The activities of hexokinase, glucokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and fructose-1,6-diphosphatase were determined in loach embryos developed in solutions of insulin, hydrocortisone, estrone and thyroxin at different stages of embryogenesis. Glucokinase and fructose-1,6-diphosphatase activties are shown not to change markedly under the influence of the above-mentioned hormones. During some periods of early development the hexokinase activity is inhibited by insulin, estrone and thyroxin. The glucose-6-phosphate dehydrogenase activity is suppressed by each of the used hormones at all the stages of early embryogenesis while the glocose-6-phosphatase activity decreased only under the influence of insulin at the cleavage, blastula and gastrula stages. Insulin increased the activity of phosphofructokinase at the cleavage, blastula and early gastrula stages and hydrocortisone, estrone and thyroxine during certain periods of these stages. From middle gastrula two last hormones decreased the phosphofructokinase activity in the loach embryos.", "contents": "[Activity of carbohydrate metabolism enzymes in loach embryos under the influence of hormones]. The activities of hexokinase, glucokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and fructose-1,6-diphosphatase were determined in loach embryos developed in solutions of insulin, hydrocortisone, estrone and thyroxin at different stages of embryogenesis. Glucokinase and fructose-1,6-diphosphatase activties are shown not to change markedly under the influence of the above-mentioned hormones. During some periods of early development the hexokinase activity is inhibited by insulin, estrone and thyroxin. The glucose-6-phosphate dehydrogenase activity is suppressed by each of the used hormones at all the stages of early embryogenesis while the glocose-6-phosphatase activity decreased only under the influence of insulin at the cleavage, blastula and gastrula stages. Insulin increased the activity of phosphofructokinase at the cleavage, blastula and early gastrula stages and hydrocortisone, estrone and thyroxine during certain periods of these stages. From middle gastrula two last hormones decreased the phosphofructokinase activity in the loach embryos."}
{"id": "PMID:194383", "title": "Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease.", "content": "The prostaglandins produce elevation of intraocular pressure and breakdown of the blood-aqueous barrier. They act via the secondary messenger system, cyclic AMP. Although the pathogenesis of many forms of ocular inflammation, both external and internal, is unclear, it is evident that some forms of ocular inflammation are prostaglandin-mediated, at least in part. Others may be totally mediated by prostaglandin synthesis. At present the corticosteroids are the mainstay of therapy of these conditions. However, the corticosteroids are poor inhibitors of prostaglandin synthesis and have many deleterious side effects such as induction of ocular hypertension, cataract, and infection. The search for new agents that will obviate these side effects and be more specific for the disease process is crucial. The discovery that the mode of action of many nonsteroidal anti-inflammatory agents is via inhibition of prostaglandin synthesis places a premium on elucidating which of these agents is most effective and least toxic in the eye and by which route of administration. The arachidonic acid screening model is ideal for initially choosing which agent has the greatest potential clinically. Arachidonic acid, a PGE2 precursor, when given topically also elevates intraocular pressure and aqueous humor protein, and these effects are blocked by the nonsteroidal anti-inflammatory drugs. This occurs if the arachidonic acid is injected into the vitreous humor, too, providing evidence that this in vivo model involves intraocular mechanisms. Utilizing the arachidonic acid system, a comparative study of nonsteroidal inhibitors of prostaglandin synthesis shows that the most effective of 14 agents were flurbiprofen solution and suspensions of polysorbate-dispersed indoxole, meclofenamic acid, indomethacin, and clonixin. Animal uveitis is not an ideal model for the human condition. Nevertheless, proving the superior efficacy of a screened drug in this system will identify those drugs to be tested in the human disease states. Only after the very few best drugs of this nature are identified should the ultimate steps of human testing be initiated.", "contents": "Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease. The prostaglandins produce elevation of intraocular pressure and breakdown of the blood-aqueous barrier. They act via the secondary messenger system, cyclic AMP. Although the pathogenesis of many forms of ocular inflammation, both external and internal, is unclear, it is evident that some forms of ocular inflammation are prostaglandin-mediated, at least in part. Others may be totally mediated by prostaglandin synthesis. At present the corticosteroids are the mainstay of therapy of these conditions. However, the corticosteroids are poor inhibitors of prostaglandin synthesis and have many deleterious side effects such as induction of ocular hypertension, cataract, and infection. The search for new agents that will obviate these side effects and be more specific for the disease process is crucial. The discovery that the mode of action of many nonsteroidal anti-inflammatory agents is via inhibition of prostaglandin synthesis places a premium on elucidating which of these agents is most effective and least toxic in the eye and by which route of administration. The arachidonic acid screening model is ideal for initially choosing which agent has the greatest potential clinically. Arachidonic acid, a PGE2 precursor, when given topically also elevates intraocular pressure and aqueous humor protein, and these effects are blocked by the nonsteroidal anti-inflammatory drugs. This occurs if the arachidonic acid is injected into the vitreous humor, too, providing evidence that this in vivo model involves intraocular mechanisms. Utilizing the arachidonic acid system, a comparative study of nonsteroidal inhibitors of prostaglandin synthesis shows that the most effective of 14 agents were flurbiprofen solution and suspensions of polysorbate-dispersed indoxole, meclofenamic acid, indomethacin, and clonixin. Animal uveitis is not an ideal model for the human condition. Nevertheless, proving the superior efficacy of a screened drug in this system will identify those drugs to be tested in the human disease states. Only after the very few best drugs of this nature are identified should the ultimate steps of human testing be initiated."}
{"id": "PMID:194389", "title": "Morphology of human cells, carrier of measles virus, using nomarski optics and scanning electron microscopy.", "content": "A human cell line (Lu106) carrier of measles virus was studied in a Nomarski interference-contrast microscope (NICM) and a scanning electron microscope (SEM). The results from this were correlated with fine structure findings obtained from analyses made in the transmission electron microscope (TEM). In both the NICM and SEM it was possible to identify intracellular perinuclear structures, which most likely represent aggregates of measles nucleocapsids. These structures appeared in the NICM as opaque vesicles and in the SEM as bulges in the flattened cells. The SEM also proved to be used for determining cell surface characteristics specific for the carrier culture, which were lacking in uninfected Lu106 cells. In the carrier culture, there were vesiculated cells with bled-like polymorphic and ridged projections, and cells with webbed cytoplasmic extensions. Ridges and transverse striations observed on these cellular protrusions and on microvilli possibly denote oriented viral nucleocapsids at the cell membrane. Furthermore in the carrier cells, the microvilli were more heterogenous in length and diameter and were more frequently branched or fused together when compared to microvilli in uninfected cells. The results are discussed in view of the available information on the appearance of virus-infected or virus-transformed cells in the SEM, also inregard to the various factors, other than virus infection, which play a role in determining the surface features of monolayer cells.", "contents": "Morphology of human cells, carrier of measles virus, using nomarski optics and scanning electron microscopy. A human cell line (Lu106) carrier of measles virus was studied in a Nomarski interference-contrast microscope (NICM) and a scanning electron microscope (SEM). The results from this were correlated with fine structure findings obtained from analyses made in the transmission electron microscope (TEM). In both the NICM and SEM it was possible to identify intracellular perinuclear structures, which most likely represent aggregates of measles nucleocapsids. These structures appeared in the NICM as opaque vesicles and in the SEM as bulges in the flattened cells. The SEM also proved to be used for determining cell surface characteristics specific for the carrier culture, which were lacking in uninfected Lu106 cells. In the carrier culture, there were vesiculated cells with bled-like polymorphic and ridged projections, and cells with webbed cytoplasmic extensions. Ridges and transverse striations observed on these cellular protrusions and on microvilli possibly denote oriented viral nucleocapsids at the cell membrane. Furthermore in the carrier cells, the microvilli were more heterogenous in length and diameter and were more frequently branched or fused together when compared to microvilli in uninfected cells. The results are discussed in view of the available information on the appearance of virus-infected or virus-transformed cells in the SEM, also inregard to the various factors, other than virus infection, which play a role in determining the surface features of monolayer cells."}
{"id": "PMID:194390", "title": "In vitro binding of 3H-estradiol to eosinophil and neutrophil granulocytes in various tissues (normal and neoplastic) of newborn and adult rats.", "content": "In vitro uptake and binding of tritiated estradiol to the specific granules of eosinophil granulocytes has been observed by ultrastructural radioautography in various tissues of the rat (liver and spleen of newborn, small intestine and bone marrow of adult animals). Binding of 3H-estradiol to granules present in the cytoplasm of neutrophil granulocytes has also been observed in bone marrow and in a cholangioma produced by chemical carcinogenesis. Neither type of granulocyte bound 3H-testosterone.", "contents": "In vitro binding of 3H-estradiol to eosinophil and neutrophil granulocytes in various tissues (normal and neoplastic) of newborn and adult rats. In vitro uptake and binding of tritiated estradiol to the specific granules of eosinophil granulocytes has been observed by ultrastructural radioautography in various tissues of the rat (liver and spleen of newborn, small intestine and bone marrow of adult animals). Binding of 3H-estradiol to granules present in the cytoplasm of neutrophil granulocytes has also been observed in bone marrow and in a cholangioma produced by chemical carcinogenesis. Neither type of granulocyte bound 3H-testosterone."}
{"id": "PMID:194391", "title": "Mitotic histiocytes and intranuclear Langerhans cell granules in histiocytosis X.", "content": "Several mitotic histiocytes containing Langerhans cell granules were found in the lymph nodes of Letterer-Siwe disease. Some histiocytes of Hand-Sch\u00fcller-Christian disease contained Langerhans cell granules within the nuclei. These Langerhans cell granules were not in 'nuclear pseudo-inclusions,' but were freely scattered inside the nuclei. We suggest that the Langerhans cell granules may get trapped in the nucleus during mitosis, since several investigators have suggested that mitosis causes other intranuclear organelles to get trapped. We also speculate that cells containing Langerhans cell granules may divide and increase by mitosis.", "contents": "Mitotic histiocytes and intranuclear Langerhans cell granules in histiocytosis X. Several mitotic histiocytes containing Langerhans cell granules were found in the lymph nodes of Letterer-Siwe disease. Some histiocytes of Hand-Sch\u00fcller-Christian disease contained Langerhans cell granules within the nuclei. These Langerhans cell granules were not in 'nuclear pseudo-inclusions,' but were freely scattered inside the nuclei. We suggest that the Langerhans cell granules may get trapped in the nucleus during mitosis, since several investigators have suggested that mitosis causes other intranuclear organelles to get trapped. We also speculate that cells containing Langerhans cell granules may divide and increase by mitosis."}
{"id": "PMID:194392", "title": "Immunoelectrophoretic investigations on Sendai virus envelope antigens in relation to host antigens.", "content": "The different antigenic fractions characteristic of egg-cultivated Sendai virus envelopes were studied by immunoelectrophoresis. Virus-specific and host-specific fractions were identified. It was proved that incorporation of the host membrane fragments into the viral envelopes is not a passive phenomenon. During the last stages of its assembly and release, the virus incorporates into the envelopes some host glycoproteins, after an active biochemical processing resulting in a considerable reduction of their molecular weight, while the host antigenic determinants remain almost unaltered.", "contents": "Immunoelectrophoretic investigations on Sendai virus envelope antigens in relation to host antigens. The different antigenic fractions characteristic of egg-cultivated Sendai virus envelopes were studied by immunoelectrophoresis. Virus-specific and host-specific fractions were identified. It was proved that incorporation of the host membrane fragments into the viral envelopes is not a passive phenomenon. During the last stages of its assembly and release, the virus incorporates into the envelopes some host glycoproteins, after an active biochemical processing resulting in a considerable reduction of their molecular weight, while the host antigenic determinants remain almost unaltered."}
{"id": "PMID:194393", "title": "The role of some viruses in acute pneumonias in adults.", "content": "Virological and bacteriological investigations were performed in 85 patients with acute pneumonias and virus isolation or serological evidence of virus infection were obtained in 37.6% of the cases. Influenza A2 and B viruses were incriminated in 14.1% of the patients; parainfluenza viruses in 7% and adenoviruses in 17.2% of the cases. Coxsackie virus was isolated from one patient's blood, and poliovirus 3 was recovered in 3 cases. In 5 cases associated virus infections were detected.", "contents": "The role of some viruses in acute pneumonias in adults. Virological and bacteriological investigations were performed in 85 patients with acute pneumonias and virus isolation or serological evidence of virus infection were obtained in 37.6% of the cases. Influenza A2 and B viruses were incriminated in 14.1% of the patients; parainfluenza viruses in 7% and adenoviruses in 17.2% of the cases. Coxsackie virus was isolated from one patient's blood, and poliovirus 3 was recovered in 3 cases. In 5 cases associated virus infections were detected."}
{"id": "PMID:194412", "title": "[Phosphoribosyl pyrophosphate and its metabolic enzymes in the erythrocytes in certain forms of anemia].", "content": "Content of phosphoribosyl pyrophosphate and the activity of ribose phosphate pyrophosphokinase and AMP-pyrophosphorylase were studied in erythrocytes of healthy persons and of patients with various types of anemia. Deficiency of phosphoribosyl pyrophosphate and a decrease in the activity of enzymes studied were observed in erythrocytes under microspherocytic and hypoplastic anemia. The alterations correlated with impairments in energy metabolism. At the same time an activation of phosphoribosyl pyrophosphate enzymatic system and an increase of its content in erythrocytes did not depend on energy metabolism in Marchiafava--Micheli disease.", "contents": "[Phosphoribosyl pyrophosphate and its metabolic enzymes in the erythrocytes in certain forms of anemia]. Content of phosphoribosyl pyrophosphate and the activity of ribose phosphate pyrophosphokinase and AMP-pyrophosphorylase were studied in erythrocytes of healthy persons and of patients with various types of anemia. Deficiency of phosphoribosyl pyrophosphate and a decrease in the activity of enzymes studied were observed in erythrocytes under microspherocytic and hypoplastic anemia. The alterations correlated with impairments in energy metabolism. At the same time an activation of phosphoribosyl pyrophosphate enzymatic system and an increase of its content in erythrocytes did not depend on energy metabolism in Marchiafava--Micheli disease."}
{"id": "PMID:194413", "title": "[Insulin-like effects of taurine].", "content": "A single administration of taurine at a dose of 200 mg per kg of body weight increased the insulin-like activity in blood plasma, elevated two-fold the content of glycogen in liver tissue, decreased content of sugars in blood. In vitro taurine increased the consumption of glucose by isolated diaphragm and increased the insulin activity. The adenilate cyclase activity was increased in incubation mixture, containing the diaphragms and taurine added. The data obtained and the recognized insulin-like effect of 3',5'-AMP and theophylline suggest that the insulin-like action of taurine is mediated through the cyclic 3',5'-AMP.", "contents": "[Insulin-like effects of taurine]. A single administration of taurine at a dose of 200 mg per kg of body weight increased the insulin-like activity in blood plasma, elevated two-fold the content of glycogen in liver tissue, decreased content of sugars in blood. In vitro taurine increased the consumption of glucose by isolated diaphragm and increased the insulin activity. The adenilate cyclase activity was increased in incubation mixture, containing the diaphragms and taurine added. The data obtained and the recognized insulin-like effect of 3',5'-AMP and theophylline suggest that the insulin-like action of taurine is mediated through the cyclic 3',5'-AMP."}
{"id": "PMID:194414", "title": "[Study of the role of endogenous 3',5'-cyclic AMP in the radioresistance of the cell].", "content": "A survival period of irradiated rat thymocytes was studied after administration of several possible modifiers of intracellular 3',5'-cyclo AMP. Theophylline, which inhibits 3',5'-cyclo AMP phosphodiesterase, adrenaline, ATP and adenosine possessed a radioprotective effect if they were added before the irradiation or just immediately after it. Imidazole activated 3',5'-cyclo AMP phosphodiesterase and, being added within the above-mentioned periods, it shortened the survival period at the irradiated cells. When theophylline and imidazole were added within 30 min after the irradiation, their effect was completely altered: imidazole increased but theophylline decreased the survival period of the irradiated cells. 3',5'-cyclo AMP and N6-2'-0-dibutyryl-3',5'-cyclo AMP did not affect the viability of thymocytes after the irradiation.", "contents": "[Study of the role of endogenous 3',5'-cyclic AMP in the radioresistance of the cell]. A survival period of irradiated rat thymocytes was studied after administration of several possible modifiers of intracellular 3',5'-cyclo AMP. Theophylline, which inhibits 3',5'-cyclo AMP phosphodiesterase, adrenaline, ATP and adenosine possessed a radioprotective effect if they were added before the irradiation or just immediately after it. Imidazole activated 3',5'-cyclo AMP phosphodiesterase and, being added within the above-mentioned periods, it shortened the survival period at the irradiated cells. When theophylline and imidazole were added within 30 min after the irradiation, their effect was completely altered: imidazole increased but theophylline decreased the survival period of the irradiated cells. 3',5'-cyclo AMP and N6-2'-0-dibutyryl-3',5'-cyclo AMP did not affect the viability of thymocytes after the irradiation."}
{"id": "PMID:194415", "title": "[Enzymatic activity of glucose-6-phosphate metabolism in the liver during the administration of a hepatic carcinogen].", "content": "In liver tissue of mice, administered with diethyl nitrosamine (2.5 mg/kg of body weight) within 2-8 months, activities of hexokinase and glucoso-6-phosphate dehydrogenase were increased and the activity of glucose-6-phosphatase was decreased . Termination of the administration of diethyl nitrosamine, which was carried out during 1-2 months, caused the temporary normalization of the enzymatic activity, but later on the alterations typical for carcinogensis were developed. After more prolonged administration of diethyl nitrosamine the period of normalization gradually disappeared. The distinct alterations in the enzymatic activity, after termination of diethyl-nitrosamine administration, were closely related to development of tumors in liver tissue.", "contents": "[Enzymatic activity of glucose-6-phosphate metabolism in the liver during the administration of a hepatic carcinogen]. In liver tissue of mice, administered with diethyl nitrosamine (2.5 mg/kg of body weight) within 2-8 months, activities of hexokinase and glucoso-6-phosphate dehydrogenase were increased and the activity of glucose-6-phosphatase was decreased . Termination of the administration of diethyl nitrosamine, which was carried out during 1-2 months, caused the temporary normalization of the enzymatic activity, but later on the alterations typical for carcinogensis were developed. After more prolonged administration of diethyl nitrosamine the period of normalization gradually disappeared. The distinct alterations in the enzymatic activity, after termination of diethyl-nitrosamine administration, were closely related to development of tumors in liver tissue."}
{"id": "PMID:194416", "title": "[Effect of cortisol on the state of adenyl cyclase system in rabbits].", "content": "Content of 3',5'-cycloAMP was estimated in rabbit blood plasma and urine; activities of adenylcyclase and phosphodiesterase were determined in liver tissue, adipose tissue and adrenal glands within 5, 24 and 48 hrs after hydrocortisone administration. Concentration of 3',5'-cycloAMP was found to be increased 4-6-fold in plasma and urine after the hormone administration. Cortisol was shown to increase also the activity of adenylcyclase and phosphodiesterase in liver tissue within 5 hrs and in adipose tissue--within 24 hrs and 48 hrs after the administration. In adrenal glands hydrocortisone caused an inhibitory effect on the adenylcyclase activity at early steps of the experiment.", "contents": "[Effect of cortisol on the state of adenyl cyclase system in rabbits]. Content of 3',5'-cycloAMP was estimated in rabbit blood plasma and urine; activities of adenylcyclase and phosphodiesterase were determined in liver tissue, adipose tissue and adrenal glands within 5, 24 and 48 hrs after hydrocortisone administration. Concentration of 3',5'-cycloAMP was found to be increased 4-6-fold in plasma and urine after the hormone administration. Cortisol was shown to increase also the activity of adenylcyclase and phosphodiesterase in liver tissue within 5 hrs and in adipose tissue--within 24 hrs and 48 hrs after the administration. In adrenal glands hydrocortisone caused an inhibitory effect on the adenylcyclase activity at early steps of the experiment."}
{"id": "PMID:194417", "title": "[Subcellular distribution of hexokinase in hepatoma and its electrophoretic properties].", "content": "In hepatomas of various malignancy contrary to normal and regenerating liver tissue a considerable part of hexokinase (HK) activity was bound with mitochondria. The HK activity, estimated in nuclei, microsomes and apparently in cytoplasma membranes, was due to contamination with mitochondrial fraction. High specific activity of HK in mitochondria of tumors might be responsible for the increased glycolysis, when these organelle preparations were added to the soluble fraction of cells. The HK of tumors was extracted from the preparations by alternative pathways. Reversible binding of some part of the enzyme with mitochondria was regulated by concentration of metabolites (ATP and G6P) similarly to the bound HK from normal tissues (brain, retina). At the same time the other part of unregulated HK activity (isozyme I only) was found in hepatomas to be intercalated into lipoprotein membranes; it was not controlled by metabolites.", "contents": "[Subcellular distribution of hexokinase in hepatoma and its electrophoretic properties]. In hepatomas of various malignancy contrary to normal and regenerating liver tissue a considerable part of hexokinase (HK) activity was bound with mitochondria. The HK activity, estimated in nuclei, microsomes and apparently in cytoplasma membranes, was due to contamination with mitochondrial fraction. High specific activity of HK in mitochondria of tumors might be responsible for the increased glycolysis, when these organelle preparations were added to the soluble fraction of cells. The HK of tumors was extracted from the preparations by alternative pathways. Reversible binding of some part of the enzyme with mitochondria was regulated by concentration of metabolites (ATP and G6P) similarly to the bound HK from normal tissues (brain, retina). At the same time the other part of unregulated HK activity (isozyme I only) was found in hepatomas to be intercalated into lipoprotein membranes; it was not controlled by metabolites."}
{"id": "PMID:194418", "title": "[Biosynthesis and properties of collagen forming in the cartilage of chick embryos in the presence of various proline analogs].", "content": "Effect of proline analogues on biosynthesis and properties of collagen in chick embryo cartilage was studied. Azethidine-2-carboxylic acid, 3,4-dehydroproline, cis-fluoro-proline, cis-hydroxyproline and thiazolidine-4-carboxylic acid were found to inhibit the incorporation of 14C-proline into proteins by 66-89%. Introduction of proline analogues, instead of the amino acid, into the polypeptide chains of collagen caused the impairment of the enzymatic hydroxylation of the proline residues (formation of hydroxyproline). 3,4-dehydroproline possessed the highest inhibitory effect (80%) on formation of hydroxyproline. When it was introduced into alpha-chains of protocollagen, 3,4-dehydroproline inhibited 1.5-6-fold the cleavage of the protein by bacterial collagenase.", "contents": "[Biosynthesis and properties of collagen forming in the cartilage of chick embryos in the presence of various proline analogs]. Effect of proline analogues on biosynthesis and properties of collagen in chick embryo cartilage was studied. Azethidine-2-carboxylic acid, 3,4-dehydroproline, cis-fluoro-proline, cis-hydroxyproline and thiazolidine-4-carboxylic acid were found to inhibit the incorporation of 14C-proline into proteins by 66-89%. Introduction of proline analogues, instead of the amino acid, into the polypeptide chains of collagen caused the impairment of the enzymatic hydroxylation of the proline residues (formation of hydroxyproline). 3,4-dehydroproline possessed the highest inhibitory effect (80%) on formation of hydroxyproline. When it was introduced into alpha-chains of protocollagen, 3,4-dehydroproline inhibited 1.5-6-fold the cleavage of the protein by bacterial collagenase."}
{"id": "PMID:194423", "title": "Transsphenoidal microsurgery for selective removal of functional pituitary microadenomas.", "content": "The transphenoidal approach to the pituitary gland is emerging as the safest and most efficacious procedure for the management of pituitary tumors. With the aid of the microscope large tumors producing visual symptoms can be removed and microadenomata producing only signs and symptoms of endocrinopathies can be safely and adequately approached. The procedure is described in this report. The results of its use in 29 patients with selected illustrative case reports are described.", "contents": "Transsphenoidal microsurgery for selective removal of functional pituitary microadenomas. The transphenoidal approach to the pituitary gland is emerging as the safest and most efficacious procedure for the management of pituitary tumors. With the aid of the microscope large tumors producing visual symptoms can be removed and microadenomata producing only signs and symptoms of endocrinopathies can be safely and adequately approached. The procedure is described in this report. The results of its use in 29 patients with selected illustrative case reports are described."}
{"id": "PMID:194425", "title": "[Determination of 11-hydroxycorticosteroids in stress-evoking interventions as an endocrinological test].", "content": "Determinations of the 11-hydroxycorticosteroids (11-OHCS) in intervention evoking stress proved as advantageous method for the estimation of the ACTH-reserve. After pneumencephalography or transethmoidal-transsphenoidal operations of the hypophysis intensive increase of 11-OHCS in the plasma and urine were observed, when the ACTH-reserve was intact. The investigations give the possibility of renouncing additional special functional tests.", "contents": "[Determination of 11-hydroxycorticosteroids in stress-evoking interventions as an endocrinological test]. Determinations of the 11-hydroxycorticosteroids (11-OHCS) in intervention evoking stress proved as advantageous method for the estimation of the ACTH-reserve. After pneumencephalography or transethmoidal-transsphenoidal operations of the hypophysis intensive increase of 11-OHCS in the plasma and urine were observed, when the ACTH-reserve was intact. The investigations give the possibility of renouncing additional special functional tests."}
{"id": "PMID:194426", "title": "E1The mechanism of action of Lupidon.", "content": "Since quite some time relapsing herpes simplex virus infections of the skin are clinically successfully treated with a heat-inactivated vaccine Lupidon G and Lupidon H respectively, although nothing is known as yet regarding the working principle of this therapy, which bases on immunological reflections. It was, therefore, examined by the complement fixing and neutralizing antibodies against herpes simplex virus of 11 patients and 3 control individuals if repeated injections of this vaccine cause alterations of the specific antibody titer. Skin tests were made in addition with 9 patient prior to and 8 weeks after therapy at the earliest. During the entire eamination period of at least 8 weeks up to 9 months the complement fixing as well as the neutralizing antibody titer remained practically constant and in none of the examined cases the skin tests caused any reaction. Since it is, however, known, e.g. from the examinations by Lehner, that seropositive individuals reacta to herpes virus with symptoms of an allergy of the delayed type, is must particularly be considered in furture examinations on the working mechanism of Lupidon that the Lupidon solutions for intracutaneous testing must be of considerably higher concentration. The questition of the site of action of Lupidon at the interferon mechanism remains pending in addition.", "contents": "E1The mechanism of action of Lupidon. Since quite some time relapsing herpes simplex virus infections of the skin are clinically successfully treated with a heat-inactivated vaccine Lupidon G and Lupidon H respectively, although nothing is known as yet regarding the working principle of this therapy, which bases on immunological reflections. It was, therefore, examined by the complement fixing and neutralizing antibodies against herpes simplex virus of 11 patients and 3 control individuals if repeated injections of this vaccine cause alterations of the specific antibody titer. Skin tests were made in addition with 9 patient prior to and 8 weeks after therapy at the earliest. During the entire eamination period of at least 8 weeks up to 9 months the complement fixing as well as the neutralizing antibody titer remained practically constant and in none of the examined cases the skin tests caused any reaction. Since it is, however, known, e.g. from the examinations by Lehner, that seropositive individuals reacta to herpes virus with symptoms of an allergy of the delayed type, is must particularly be considered in furture examinations on the working mechanism of Lupidon that the Lupidon solutions for intracutaneous testing must be of considerably higher concentration. The questition of the site of action of Lupidon at the interferon mechanism remains pending in addition."}
{"id": "PMID:194427", "title": "[Therapy of recurrent herpes simplex].", "content": "The topical and systemic possibilities of treatment of herpes simplex recidivans are discussed in a brief report. The antigen therapy with Lupidon is mentioned in detail. A selection of important clinical reports on Lupidon is commented. These reports demonstrate a good to very good therapeutic effect of Lupidon in relapsing herpes simplex with more than 1500 controlled patients. A statistically confirmed result of the long-term antigen therapy with Lupidon was particularly demonstrated in controlled double blank tests. Up to now there were not observed any severe side effects with this great number of patients.", "contents": "[Therapy of recurrent herpes simplex]. The topical and systemic possibilities of treatment of herpes simplex recidivans are discussed in a brief report. The antigen therapy with Lupidon is mentioned in detail. A selection of important clinical reports on Lupidon is commented. These reports demonstrate a good to very good therapeutic effect of Lupidon in relapsing herpes simplex with more than 1500 controlled patients. A statistically confirmed result of the long-term antigen therapy with Lupidon was particularly demonstrated in controlled double blank tests. Up to now there were not observed any severe side effects with this great number of patients."}
{"id": "PMID:194435", "title": "[Long-term effect of hormonal contraceptives on the behavior of serum lipids].", "content": "In order to check the long-term effects of oral contraceptives used in the GDR on certain serum-lipid-fractions, triglycerides, phospholipids, total and free cholesterol, and beta-lipoproteins were determined in four groups of 15 women each, taking the contraceptive preparations Ovosiston, Nonovlon, Gravistat, and Deposiston. Determinations were carried out before and following 3, 6, 12, and 18 month of drug administration. Statistically significant increases of triglycerides occurred under the combined preparations, of phospholipids under Ovosiston and Deposiston and of the beta-lipoproteins under Ovosiston and Gravistat. Total cholesterol showed a slight decrease under all preparations tested. At present the prognostic significance of these slight alterations of serum-lipid-concentrations cannot be estimated completely.", "contents": "[Long-term effect of hormonal contraceptives on the behavior of serum lipids]. In order to check the long-term effects of oral contraceptives used in the GDR on certain serum-lipid-fractions, triglycerides, phospholipids, total and free cholesterol, and beta-lipoproteins were determined in four groups of 15 women each, taking the contraceptive preparations Ovosiston, Nonovlon, Gravistat, and Deposiston. Determinations were carried out before and following 3, 6, 12, and 18 month of drug administration. Statistically significant increases of triglycerides occurred under the combined preparations, of phospholipids under Ovosiston and Deposiston and of the beta-lipoproteins under Ovosiston and Gravistat. Total cholesterol showed a slight decrease under all preparations tested. At present the prognostic significance of these slight alterations of serum-lipid-concentrations cannot be estimated completely."}
{"id": "PMID:194432", "title": "[Neurophysiologic analysis of the effect of ACTH and hydrocortisone on conditioned reflex behavior in cats].", "content": "In defensive behaviour of cats, ACTH eliminated extinction delay, evoked by electrical stimulation (with constant parameters) of the midbrain reticular formation, and enhanced the activating influence of the thalamus reticular zone. Hydrocortisone produced opposite effects. In alimentary behaviour, the adaptive hormones enhanced the facilitating effect on extinction, induced by stimulation of non-specific structures and the hypothalamus. However, during hydrocortisone action, encephalographic signs of the reflex remained for a long time after extinction of effector manifestations. Thus, ACTH and hydrocortizone, by changing the interaction between brain structures, exert certain influences on the behavioral processes. The hormonal effects, in turn, depend on the initial co-excitation of the centres.", "contents": "[Neurophysiologic analysis of the effect of ACTH and hydrocortisone on conditioned reflex behavior in cats]. In defensive behaviour of cats, ACTH eliminated extinction delay, evoked by electrical stimulation (with constant parameters) of the midbrain reticular formation, and enhanced the activating influence of the thalamus reticular zone. Hydrocortisone produced opposite effects. In alimentary behaviour, the adaptive hormones enhanced the facilitating effect on extinction, induced by stimulation of non-specific structures and the hypothalamus. However, during hydrocortisone action, encephalographic signs of the reflex remained for a long time after extinction of effector manifestations. Thus, ACTH and hydrocortizone, by changing the interaction between brain structures, exert certain influences on the behavioral processes. The hormonal effects, in turn, depend on the initial co-excitation of the centres."}
{"id": "PMID:194436", "title": "Electron-microscopical observations on the development of vaccinia, cowpox and monkeypox viruses in pig skin.", "content": "Multiformal abnormal configurations of virus particles and virus factories were observed in pig skin inoculated with vaccinia, cowpox and monkeypox viruses. The discussion is based on the data of multiplication of the viruses and production of circulating antibody.", "contents": "Electron-microscopical observations on the development of vaccinia, cowpox and monkeypox viruses in pig skin. Multiformal abnormal configurations of virus particles and virus factories were observed in pig skin inoculated with vaccinia, cowpox and monkeypox viruses. The discussion is based on the data of multiplication of the viruses and production of circulating antibody."}
{"id": "PMID:194433", "title": "[Biochemical characteristics of subcellular components of the visual system following light deprivation].", "content": "A study was made of the influence of prolonged light deprivation (ten weeks) at early stages of the rabbit postnatal ontogenesis on the state of specific enzyme activity (of cytochromoxidase, AChEase, K-Na-ATPase, monoaminoxidase and ATPase) in the synaptosomes and cellular mitochondria of the visual cortex and superior colliculi. A specific and oppositely directed change has been found ro each enzyme and subcellular structures. Restoration of sensory impulse activity in two weeks was attended with normalization of the revealed metabolism changes, likewise dissimilar for different subcellular components.", "contents": "[Biochemical characteristics of subcellular components of the visual system following light deprivation]. A study was made of the influence of prolonged light deprivation (ten weeks) at early stages of the rabbit postnatal ontogenesis on the state of specific enzyme activity (of cytochromoxidase, AChEase, K-Na-ATPase, monoaminoxidase and ATPase) in the synaptosomes and cellular mitochondria of the visual cortex and superior colliculi. A specific and oppositely directed change has been found ro each enzyme and subcellular structures. Restoration of sensory impulse activity in two weeks was attended with normalization of the revealed metabolism changes, likewise dissimilar for different subcellular components."}
{"id": "PMID:194439", "title": "[Effect of alcoholic intoxication on the body's natural resistance to exposure to infectious and toxic agents].", "content": "The influence of alcoholic intoxication on the resistance of albino mice to bacterial toxins and staphylococcus cultures was investigated. Five-day administration of 40% ethyl alcohol to the animals was accompanied by a significant increase of their resistance to the intoxication caused by C1. perfringens toxins and staphylococcus. Thirty-day alcoholic intoxication promoted a marked reduction of albino mice resistance to the both toxins used and the staphylococcus cultures.", "contents": "[Effect of alcoholic intoxication on the body's natural resistance to exposure to infectious and toxic agents]. The influence of alcoholic intoxication on the resistance of albino mice to bacterial toxins and staphylococcus cultures was investigated. Five-day administration of 40% ethyl alcohol to the animals was accompanied by a significant increase of their resistance to the intoxication caused by C1. perfringens toxins and staphylococcus. Thirty-day alcoholic intoxication promoted a marked reduction of albino mice resistance to the both toxins used and the staphylococcus cultures."}
{"id": "PMID:194440", "title": "Interaction of elongation factor 2 from wheat germ with guanosine nucleotides and ribosomes.", "content": "1. The amino acid composition of wheat germ EF2 differs to some extent from that of elongation factors from mammals and bacteria. 2. The purified wheat germ EF2, similarly as the factors from other sources, is active in the: EF1-dependent polymerization of phenylalanine; ribosome-dependent GTP hydrolysis; binding of guanosine nucleotides; and ADP-ribosylation in the presence of diphtheria toxin. Fusidic acid at a concentration of 1 mM inhibits all these EF2-dependent reactions. 3. Diphtheria toxin in the presence of NAD+ inhibits polymerization of phenylalanine but does not effect GTP binding to EF2. 4. Binding of GDP to wheat germ EF2 is inhibited by ribosomes. During interaction with ribosomes, GTP in EF2-GTP complex is rapidly hydrolysed to GDP. Both GTP and 5'-guanylmethylenediphosphonate competitively inhibit formation of the ribosome-EF2-GDP complex due to the replacement of GDP from the complex. The latter is stabilized by fusidic acid.", "contents": "Interaction of elongation factor 2 from wheat germ with guanosine nucleotides and ribosomes. 1. The amino acid composition of wheat germ EF2 differs to some extent from that of elongation factors from mammals and bacteria. 2. The purified wheat germ EF2, similarly as the factors from other sources, is active in the: EF1-dependent polymerization of phenylalanine; ribosome-dependent GTP hydrolysis; binding of guanosine nucleotides; and ADP-ribosylation in the presence of diphtheria toxin. Fusidic acid at a concentration of 1 mM inhibits all these EF2-dependent reactions. 3. Diphtheria toxin in the presence of NAD+ inhibits polymerization of phenylalanine but does not effect GTP binding to EF2. 4. Binding of GDP to wheat germ EF2 is inhibited by ribosomes. During interaction with ribosomes, GTP in EF2-GTP complex is rapidly hydrolysed to GDP. Both GTP and 5'-guanylmethylenediphosphonate competitively inhibit formation of the ribosome-EF2-GDP complex due to the replacement of GDP from the complex. The latter is stabilized by fusidic acid."}
{"id": "PMID:194437", "title": "[Comparative-biochemical study of phosphoinositides as functionally active components of excitable nerve fiber membranes].", "content": "The effect of acetylcholine (ACh) and cyclic 3',5'-adenosine monophosphate (cAMP) on phosphoinositide (PI) metabolism and associated changes of the permeability of the nervous fibers in the crustaceans Carcinum maenas and Eriphia spinifrons, as well as in the frog Rana temporaria, has been investigated. It was shown that ACh induces a significant decrease in the content of triphosphoinositides (TPI) in the nervous fibers of the crabs and increases their potassium permeability, which in its turn results in depolarization of the fibers. ACh did not affect frog nervous fibers. cAMP significantly increases the incorporation of 32P into TPI fraction of crab nervous fibers during conduction of excitation and also facilitates repolarization of the fibers after application of ACh. Proserine effectively protects nervous fibers from the influence of ACh, indicating possible participation of acetylcholinesterase in TPI hydrolysis. The data obtained suggest that PI are involved into the regulation of membrane permeability of crab nervous fibers to potassium ions.", "contents": "[Comparative-biochemical study of phosphoinositides as functionally active components of excitable nerve fiber membranes]. The effect of acetylcholine (ACh) and cyclic 3',5'-adenosine monophosphate (cAMP) on phosphoinositide (PI) metabolism and associated changes of the permeability of the nervous fibers in the crustaceans Carcinum maenas and Eriphia spinifrons, as well as in the frog Rana temporaria, has been investigated. It was shown that ACh induces a significant decrease in the content of triphosphoinositides (TPI) in the nervous fibers of the crabs and increases their potassium permeability, which in its turn results in depolarization of the fibers. ACh did not affect frog nervous fibers. cAMP significantly increases the incorporation of 32P into TPI fraction of crab nervous fibers during conduction of excitation and also facilitates repolarization of the fibers after application of ACh. Proserine effectively protects nervous fibers from the influence of ACh, indicating possible participation of acetylcholinesterase in TPI hydrolysis. The data obtained suggest that PI are involved into the regulation of membrane permeability of crab nervous fibers to potassium ions."}
{"id": "PMID:194441", "title": "Analysis of diameters of human pituitary hormone secretory granules.", "content": "Measurements were made on electron micrographs of six human anterior pituitary glands of the maximal diameters of secretory granules in 130 cells, average 91 granules per cell. This was done in an attempt to classify the various hormone types solely by differences in the mean diameters of the secretory granules. The range of diameters in nanometers could be segregated into six subgroups of the following suggested functions: 135.5 +/- 13.6 TSH, 181.6 +/- 9.3 LH, 226.0 +/- 19.4 FSH, 356.8 +/- 30.5 ACTH/MSH, 452.9 +/- 23.8 GH, 559.9 +/- 38.0 prolactin.", "contents": "Analysis of diameters of human pituitary hormone secretory granules. Measurements were made on electron micrographs of six human anterior pituitary glands of the maximal diameters of secretory granules in 130 cells, average 91 granules per cell. This was done in an attempt to classify the various hormone types solely by differences in the mean diameters of the secretory granules. The range of diameters in nanometers could be segregated into six subgroups of the following suggested functions: 135.5 +/- 13.6 TSH, 181.6 +/- 9.3 LH, 226.0 +/- 19.4 FSH, 356.8 +/- 30.5 ACTH/MSH, 452.9 +/- 23.8 GH, 559.9 +/- 38.0 prolactin."}
{"id": "PMID:194442", "title": "Studies on the mechanisms of somatostatin action on insulin release. IV. effect of somatostatin on cyclic AMP levels and phosphodiesterase activity in isolated rat pancreatic islets.", "content": "The effects of somatostatin on insulin release and cyclic AMP metabolism were studied in collagenase-isolated islets of Langerhans from the rat. Ceoncentrations from 500 to 2000 ng/ml significantly inhibited glucose stimulated insulin release, while 100 and 200 ng/ml were ineffective. Somatostatin (2000 ng/ml) inhibited insulin release and [3H]-cyclic AMP accumulation induced by 16.7 mM glucose after 10 and 30 min of incubation. In dose-response studies, the inhibition by somatostatin of the effect of glucose on [3H]cyclic AMP and insulin release could be overcome by a high concentration of the hexose (44.9 mM), suggesting competitive inhibition. In the absence of glucose, somatostatin inhibited [3H]cyclic AMP accumulation induced by the phosphodiesterase inhibitor, IBMX, while no inhibition was seen, again in the absence of hexose, when the [3H]cyclic AMP levels had been raised by the adenyl cyclase stimulator, cholera toxin. Somatostatin did not affect phosphodiesterase activity when added to islet homogenates, but preincubation of the islets with the peptide before homogenization decreased the activity by about 30%. It is suggested that somatostatin-induced inhibition of insulin release is, at least partially, mediated by cyclic AMP, probably through an action on islet adenyl cyclase.", "contents": "Studies on the mechanisms of somatostatin action on insulin release. IV. effect of somatostatin on cyclic AMP levels and phosphodiesterase activity in isolated rat pancreatic islets. The effects of somatostatin on insulin release and cyclic AMP metabolism were studied in collagenase-isolated islets of Langerhans from the rat. Ceoncentrations from 500 to 2000 ng/ml significantly inhibited glucose stimulated insulin release, while 100 and 200 ng/ml were ineffective. Somatostatin (2000 ng/ml) inhibited insulin release and [3H]-cyclic AMP accumulation induced by 16.7 mM glucose after 10 and 30 min of incubation. In dose-response studies, the inhibition by somatostatin of the effect of glucose on [3H]cyclic AMP and insulin release could be overcome by a high concentration of the hexose (44.9 mM), suggesting competitive inhibition. In the absence of glucose, somatostatin inhibited [3H]cyclic AMP accumulation induced by the phosphodiesterase inhibitor, IBMX, while no inhibition was seen, again in the absence of hexose, when the [3H]cyclic AMP levels had been raised by the adenyl cyclase stimulator, cholera toxin. Somatostatin did not affect phosphodiesterase activity when added to islet homogenates, but preincubation of the islets with the peptide before homogenization decreased the activity by about 30%. It is suggested that somatostatin-induced inhibition of insulin release is, at least partially, mediated by cyclic AMP, probably through an action on islet adenyl cyclase."}
{"id": "PMID:194443", "title": "Physiological regulation of rat liver phosphoenolpyruvate carboxykinase (GTP) by insulin. Insignificance of a cyclic AMP-independent mechanism.", "content": "The effect of re-feeding glucose, protein or fat and the effect of insulin injection on the activity of hepatic phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating) EC 4.1.1.32), the concentration of hepatic cyclic AMP and the level of serum insulin was investigated in starved rats. Under all conditions examined the concentration of serum insulin was elevated to a high degree. However, only rats re-fed with glucose responded to the increase in serum insulin with a decrease in PEP carboxykinase activity, while the activity of the enzyme remained unchanged or was elevated after re-feeding protein or fat or after insulin injection, respectively. Since under all conditions there was a close correlation between cyclic AMP concentration and PEP carboxykinase activity, but not between the insulin level and enzyme activity, it is concluded that the hormone physiologically regulates PEP carboxykinase activity by decreasing the intrahepatic cyclic AMP concentration rather than by the postulated cyclic AMP-independent inhibition of specific mRNA translation.", "contents": "Physiological regulation of rat liver phosphoenolpyruvate carboxykinase (GTP) by insulin. Insignificance of a cyclic AMP-independent mechanism. The effect of re-feeding glucose, protein or fat and the effect of insulin injection on the activity of hepatic phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating) EC 4.1.1.32), the concentration of hepatic cyclic AMP and the level of serum insulin was investigated in starved rats. Under all conditions examined the concentration of serum insulin was elevated to a high degree. However, only rats re-fed with glucose responded to the increase in serum insulin with a decrease in PEP carboxykinase activity, while the activity of the enzyme remained unchanged or was elevated after re-feeding protein or fat or after insulin injection, respectively. Since under all conditions there was a close correlation between cyclic AMP concentration and PEP carboxykinase activity, but not between the insulin level and enzyme activity, it is concluded that the hormone physiologically regulates PEP carboxykinase activity by decreasing the intrahepatic cyclic AMP concentration rather than by the postulated cyclic AMP-independent inhibition of specific mRNA translation."}
{"id": "PMID:194444", "title": "Extremely high levels of corticosteroids and low levels of corticosteroid binding macromolecule in plasma of marmoset monkeys.", "content": "Marmoset monkeys were shown to have extremely high resting plasma corticosteroid levels compared to those of macaque monkeys and humans. A major component of corticosteroids seems to be cortisol. Levels of total 11-deoxy-17-KS in plasma of marmoset monkeys were very low (less than 0.01-0.04 microng/ml). Following the injection of ACTH, plasma corticosteroid levels of marmoset monkeys increased by 18-62% (at 1 h), and by 62-160% (at 2 h). Concentrations of plasma corticosteroid binding macromolecule in marmoset monkeys were extremely low (less than 10 nM). It was suggested that in these monkeys, the majority of plasma corticosteroids exists in non-protein bound forms.", "contents": "Extremely high levels of corticosteroids and low levels of corticosteroid binding macromolecule in plasma of marmoset monkeys. Marmoset monkeys were shown to have extremely high resting plasma corticosteroid levels compared to those of macaque monkeys and humans. A major component of corticosteroids seems to be cortisol. Levels of total 11-deoxy-17-KS in plasma of marmoset monkeys were very low (less than 0.01-0.04 microng/ml). Following the injection of ACTH, plasma corticosteroid levels of marmoset monkeys increased by 18-62% (at 1 h), and by 62-160% (at 2 h). Concentrations of plasma corticosteroid binding macromolecule in marmoset monkeys were extremely low (less than 10 nM). It was suggested that in these monkeys, the majority of plasma corticosteroids exists in non-protein bound forms."}
{"id": "PMID:194445", "title": "The effect of calcium and dibutryl-cAMP on the secretion of parathyroid hormone by human parathyroid adenomas in organ culture.", "content": "The effect of different calcium concentrations as well as dibutyryl-cyclic adenosine 3',5'-monophosphate (DB-cAMP) on the secretion of parathyroid hormone by human parathyroid adenomas taken from patients with primary hyperparathyroidism (pHPT) was studied in organ culture. Their influence on the release of hormone was determined. The tissue was incubated in culture medium for 4 h; the medium was changed hourly and analyzed for immunoreactive parathyroid hormone (PTH) by radioimmunoassay. The hormone secretion showed an inverse relationship to different calcium concentrations in the medium and could be stimulated independently of the calcium concentration by adding DB-cAMP. These results suggest that the examined parathyroid adenomas are sensitive to physiological stimuli.", "contents": "The effect of calcium and dibutryl-cAMP on the secretion of parathyroid hormone by human parathyroid adenomas in organ culture. The effect of different calcium concentrations as well as dibutyryl-cyclic adenosine 3',5'-monophosphate (DB-cAMP) on the secretion of parathyroid hormone by human parathyroid adenomas taken from patients with primary hyperparathyroidism (pHPT) was studied in organ culture. Their influence on the release of hormone was determined. The tissue was incubated in culture medium for 4 h; the medium was changed hourly and analyzed for immunoreactive parathyroid hormone (PTH) by radioimmunoassay. The hormone secretion showed an inverse relationship to different calcium concentrations in the medium and could be stimulated independently of the calcium concentration by adding DB-cAMP. These results suggest that the examined parathyroid adenomas are sensitive to physiological stimuli."}
{"id": "PMID:194446", "title": "Studies on the mechanism of somatostatin action on insulin release. V. Effect of somatostatin analogues on arginine induced release of insulin and glucagon from the perfused rat pancreas.", "content": "Eighteen analogues of somatostatin have been used in order to elucidate the structure-activity relationship of the peptide on the release of insulin and glucagon from the isolated perfused rat pancreas. Neither the amino terminal nor a free carboxyl terminal seemed to be essential for the activity of the cyclic peptide. Addition of amino acids to the amino terminal did not decrease the activity. On the other hand, minor changes in the structure of linear somatostatin, which lead to the loss of ability to form a cyclic peptide, impaired the activity. Deletion of Asn5 was accompanied by decreased action on glucagon but not on insulin release. It seems that the major actions of somatostatin on the pancreas are bound to the amino acid sequence 4-13 in the molecule and to the ability of the molecule to cyclize.", "contents": "Studies on the mechanism of somatostatin action on insulin release. V. Effect of somatostatin analogues on arginine induced release of insulin and glucagon from the perfused rat pancreas. Eighteen analogues of somatostatin have been used in order to elucidate the structure-activity relationship of the peptide on the release of insulin and glucagon from the isolated perfused rat pancreas. Neither the amino terminal nor a free carboxyl terminal seemed to be essential for the activity of the cyclic peptide. Addition of amino acids to the amino terminal did not decrease the activity. On the other hand, minor changes in the structure of linear somatostatin, which lead to the loss of ability to form a cyclic peptide, impaired the activity. Deletion of Asn5 was accompanied by decreased action on glucagon but not on insulin release. It seems that the major actions of somatostatin on the pancreas are bound to the amino acid sequence 4-13 in the molecule and to the ability of the molecule to cyclize."}
{"id": "PMID:194447", "title": "Lack of effect of prolactin inhibition by alpha-bromoergocriptine (CB 154) on plasma aldosterone in anephric and non-nephrectomized patients on regular haemodialysis.", "content": "To investigate whether a direct influence exists between the prolactin suppressive effect of alpha-bromoergocriptine (CB 154) and the aldosterone response to a potassium stimulation, the present study was performed in 7 anephric patients and in 7 non-nephrectomized patients, all on regular haemodialysis. The increase in the plasma potassium concentration between dialysis was used as a stimulus to the adrenals, and was correlated to the increase in the plasma aldosterone concentration (PAC). Plasma samples were obtained during a control period and during a corresponding period of treatment with bromocriptine. Despite a significant fall in the prolactin levels during the bromocriptine treatment, no differences in the aldosterone response to the increasing potassium concentration in the two periods were found neither in the anephric nor in the non-nephrectomized patients. It is concluded that depression of prolactin levels by the dopamine agonist (bromocriptine) has no influence on the ability of the adrenals to react with an increase in aldosterone secretion following potassium stimulation in dialysis patients with and without preserved renin-angiotensin system.", "contents": "Lack of effect of prolactin inhibition by alpha-bromoergocriptine (CB 154) on plasma aldosterone in anephric and non-nephrectomized patients on regular haemodialysis. To investigate whether a direct influence exists between the prolactin suppressive effect of alpha-bromoergocriptine (CB 154) and the aldosterone response to a potassium stimulation, the present study was performed in 7 anephric patients and in 7 non-nephrectomized patients, all on regular haemodialysis. The increase in the plasma potassium concentration between dialysis was used as a stimulus to the adrenals, and was correlated to the increase in the plasma aldosterone concentration (PAC). Plasma samples were obtained during a control period and during a corresponding period of treatment with bromocriptine. Despite a significant fall in the prolactin levels during the bromocriptine treatment, no differences in the aldosterone response to the increasing potassium concentration in the two periods were found neither in the anephric nor in the non-nephrectomized patients. It is concluded that depression of prolactin levels by the dopamine agonist (bromocriptine) has no influence on the ability of the adrenals to react with an increase in aldosterone secretion following potassium stimulation in dialysis patients with and without preserved renin-angiotensin system."}
{"id": "PMID:194449", "title": "Effects of ACTH and dexamethasone on the zona glomerulosa of the rat adrenal cortex: an ultrastructural stereologic study.", "content": "The effects of a chronic treatment with ACTH and dexamethasone on the zona glomerulosa of intact rat adrenals were investigated by morphometric methods and electron microscopy. It was found that ACTH increases the volume of the zona glomerulosa, of the cells, nuclei mitochondrial compartment as well as the surface of SER and mitochondrial compartment as well as the surface of SER and mitochondrial cristae. Also noticeable was the hypertrophy of the Golgi apparatus. Opposite effects were obtained after dexamethasone treatment. These findings are interpreted as indicating that ACTH is involved in the maintenance and stimulation of the growth and steroidogenic capacity of the adrenal zona glomerulosa.", "contents": "Effects of ACTH and dexamethasone on the zona glomerulosa of the rat adrenal cortex: an ultrastructural stereologic study. The effects of a chronic treatment with ACTH and dexamethasone on the zona glomerulosa of intact rat adrenals were investigated by morphometric methods and electron microscopy. It was found that ACTH increases the volume of the zona glomerulosa, of the cells, nuclei mitochondrial compartment as well as the surface of SER and mitochondrial compartment as well as the surface of SER and mitochondrial cristae. Also noticeable was the hypertrophy of the Golgi apparatus. Opposite effects were obtained after dexamethasone treatment. These findings are interpreted as indicating that ACTH is involved in the maintenance and stimulation of the growth and steroidogenic capacity of the adrenal zona glomerulosa."}
{"id": "PMID:194450", "title": "Demonstration of an FSH receptor in a functioning granulosa cell tumour. The effect of gonadotrophin treatment on its viability following transplantation to nude mice.", "content": "Hormone production in a patient suffering from a late recurrence of a granulosa cell tumour has been studied pre- and post-operatively, and a vein on the tumour surface was cannulated at operation to collect tumour vein blood for pre-operative studies. Elevation in the plasma oestradiol level and depression in FSH and LH were found pre-operatively, and elevations were found in tumour vein oestradiol and 17alpha-hydroxyprogsterone. Plasma oestradiol level returned to normal postoperatively whereas FSH and LH levels were persistently depressed. FSH receptors were found in this tumour, and on the basis of this finding, gonadotrophins were given to athymic nude mice in an attempt to support the growth of the granulosa cell tumour implanted in these animals. We demonstrated that gonadotrophins have supported the tumour tissue, but not promoted growth.", "contents": "Demonstration of an FSH receptor in a functioning granulosa cell tumour. The effect of gonadotrophin treatment on its viability following transplantation to nude mice. Hormone production in a patient suffering from a late recurrence of a granulosa cell tumour has been studied pre- and post-operatively, and a vein on the tumour surface was cannulated at operation to collect tumour vein blood for pre-operative studies. Elevation in the plasma oestradiol level and depression in FSH and LH were found pre-operatively, and elevations were found in tumour vein oestradiol and 17alpha-hydroxyprogsterone. Plasma oestradiol level returned to normal postoperatively whereas FSH and LH levels were persistently depressed. FSH receptors were found in this tumour, and on the basis of this finding, gonadotrophins were given to athymic nude mice in an attempt to support the growth of the granulosa cell tumour implanted in these animals. We demonstrated that gonadotrophins have supported the tumour tissue, but not promoted growth."}
{"id": "PMID:194452", "title": "Erythrocyte galactose-1-phosphate uridyltransferase and galactokinase levels in twins.", "content": "The levels of the two enzymes, GAL-1-PUT and GAL-KIN, have been examined in a sample of 35 MZ and 45 DZ twin pairs of both sexes. The activities of these enzymes do not appear to be influenced by sex. The role of genetic factors appears to be rather limited in the case of GAL-1-PUT, but much higher in the case of GAL-KIN.", "contents": "Erythrocyte galactose-1-phosphate uridyltransferase and galactokinase levels in twins. The levels of the two enzymes, GAL-1-PUT and GAL-KIN, have been examined in a sample of 35 MZ and 45 DZ twin pairs of both sexes. The activities of these enzymes do not appear to be influenced by sex. The role of genetic factors appears to be rather limited in the case of GAL-1-PUT, but much higher in the case of GAL-KIN."}
{"id": "PMID:194453", "title": "Transmission of excitation from muscle to nerve under in situ conditions.", "content": "In order to investigate the excitatory effect of the muscle on the adjacent nerve experiments were performed on nerve-muscle and whole leg preparations of the frog. The results showed that muscular activity could generate excitation of the nerve in contact with the muscle under in situ circumstances, and that a well-defined part of the muscle could play a significant role in the transmission of excitation from muscle to nerve. The results support the hypothesis of being an additional way for muscle activity to influence the regulatory mechanism of the nerve-muscle function during excitatory processes.", "contents": "Transmission of excitation from muscle to nerve under in situ conditions. In order to investigate the excitatory effect of the muscle on the adjacent nerve experiments were performed on nerve-muscle and whole leg preparations of the frog. The results showed that muscular activity could generate excitation of the nerve in contact with the muscle under in situ circumstances, and that a well-defined part of the muscle could play a significant role in the transmission of excitation from muscle to nerve. The results support the hypothesis of being an additional way for muscle activity to influence the regulatory mechanism of the nerve-muscle function during excitatory processes."}
{"id": "PMID:194454", "title": "The clinical classification of maculopathies in adults. A survey.", "content": "The development of fluorescein angiography and the introduction of laser technology into the treatment of macular diseases has considerably widened our knowledge of the pathological processes in the macular region. A number of clinicopathological reports have confirmed the angiographic findings and interpretations. The aetiological factors that lay behind the clinical lesions are, however, still unknown. The clinical pictures have, as a result of the above, more relation to the histological than to the aetiological classifications. Clinical classification includes an analysis and categorization of the individual diseases. This process takes place daily in the surgery of every ophthalmologist by means of the ophthalmoscope. The ophthalmoscopical examination is enhanced by knowledge of the angiographic picture of the lesion. This means that in the great majority of cases it is possible using the ophthalmoscope alone, to evaluate the type and anatomical localization of the pathological lesions. Fluorescein angiography is the most important single supplementary examination, both with regard to the diagnosis, indication for treatment and the follow-up. The present work describes 9 clinically and histopathologically well-defined lesions, which isolated or in combination are seen in the majority of adult macular diseases.", "contents": "The clinical classification of maculopathies in adults. A survey. The development of fluorescein angiography and the introduction of laser technology into the treatment of macular diseases has considerably widened our knowledge of the pathological processes in the macular region. A number of clinicopathological reports have confirmed the angiographic findings and interpretations. The aetiological factors that lay behind the clinical lesions are, however, still unknown. The clinical pictures have, as a result of the above, more relation to the histological than to the aetiological classifications. Clinical classification includes an analysis and categorization of the individual diseases. This process takes place daily in the surgery of every ophthalmologist by means of the ophthalmoscope. The ophthalmoscopical examination is enhanced by knowledge of the angiographic picture of the lesion. This means that in the great majority of cases it is possible using the ophthalmoscope alone, to evaluate the type and anatomical localization of the pathological lesions. Fluorescein angiography is the most important single supplementary examination, both with regard to the diagnosis, indication for treatment and the follow-up. The present work describes 9 clinically and histopathologically well-defined lesions, which isolated or in combination are seen in the majority of adult macular diseases."}
{"id": "PMID:194456", "title": "Mesenteric vascular occlusion in infants and children: report of two cases and review of the literature.", "content": "Mesenteric vascular occlusion is a rare disease in the paediatric age group. The pertaining literature is reviewed and two cases are reported. In the first one the vascular obstruction developed after a Wilms tumour on the right side had been removed. Following bowel resection and end-to-end anastomosis the patient died of uraemia. Post mortem examination revealed a diffuse membranous glomerulonephritis and pseudoxanthomatosis in the remaining left kidney, the function of which had probably been affected by the shock associated with mesenteric thrombosis. In the second case a mixed mesenteric vascular occlusion was found without any previous disease; after ileal resection and ileo-coecal anastomosis the baby made a smooth recovery.", "contents": "Mesenteric vascular occlusion in infants and children: report of two cases and review of the literature. Mesenteric vascular occlusion is a rare disease in the paediatric age group. The pertaining literature is reviewed and two cases are reported. In the first one the vascular obstruction developed after a Wilms tumour on the right side had been removed. Following bowel resection and end-to-end anastomosis the patient died of uraemia. Post mortem examination revealed a diffuse membranous glomerulonephritis and pseudoxanthomatosis in the remaining left kidney, the function of which had probably been affected by the shock associated with mesenteric thrombosis. In the second case a mixed mesenteric vascular occlusion was found without any previous disease; after ileal resection and ileo-coecal anastomosis the baby made a smooth recovery."}
{"id": "PMID:194457", "title": "Severe disseminated adenovirus infection successfully treated with a thymic humoral factor, THF.", "content": "Adenovirus and other usually benign viral infections may occasionally be associated with severe fulminant disease, often accompanied by acute acquired cellular immunodeficiency. Thymic humoral factor derived from calf thymuses has been demonstrated to have the capacity to restore the immunocompetence of immature, incompetent T cells. This factor was used in the treatment of a 3 1/2-year-old boy who was critically ill with an adenovirus infection and presented evidence of immunocellular deficiency. Within less than 48 hours after the institution of treatment with thymic humoral factor there was a dramatic, progressive clinical improvement, with restoration of the cellular immunocompetence. It is suggested that thymic humoral factor may be beneficial in the treatment of severe viral infections associated with depressed cellular immunocompetence.", "contents": "Severe disseminated adenovirus infection successfully treated with a thymic humoral factor, THF. Adenovirus and other usually benign viral infections may occasionally be associated with severe fulminant disease, often accompanied by acute acquired cellular immunodeficiency. Thymic humoral factor derived from calf thymuses has been demonstrated to have the capacity to restore the immunocompetence of immature, incompetent T cells. This factor was used in the treatment of a 3 1/2-year-old boy who was critically ill with an adenovirus infection and presented evidence of immunocellular deficiency. Within less than 48 hours after the institution of treatment with thymic humoral factor there was a dramatic, progressive clinical improvement, with restoration of the cellular immunocompetence. It is suggested that thymic humoral factor may be beneficial in the treatment of severe viral infections associated with depressed cellular immunocompetence."}
{"id": "PMID:194458", "title": "Cord serum lipid and lipoprotein-cholesterol values in normal and betamethasone-treated newborns of varying gestational age.", "content": "Cord serum total cholesterol, very low density lipoprotein-, low density lipoprotein-, high density lipoprotein-cholesterol and triglyceride was determined in 30 AGA infants and 35 SGA infants born between the larger than or equal to 37th less than or equal to 42th week of gestation and in 26 AGA infants born between the larger than or equal to 33th less than 37th week of gestation. In SGA infants significantly higher VLDL-cholesterol and triglyceride values were found than in AGA infants. In AGA infants less than 37 weeks of gestation total cholesterol, LDL-, and HDL-cholesterol concentrations were higher than in AGA infants larger than or equal to 37 weeks of gestation. In 10 betamethasone-treated AGA infants less than 37 weeks of gestation HDL-cholesterol was higher than in 16 untreated AGA infants less than 37 weeks of gestation.", "contents": "Cord serum lipid and lipoprotein-cholesterol values in normal and betamethasone-treated newborns of varying gestational age. Cord serum total cholesterol, very low density lipoprotein-, low density lipoprotein-, high density lipoprotein-cholesterol and triglyceride was determined in 30 AGA infants and 35 SGA infants born between the larger than or equal to 37th less than or equal to 42th week of gestation and in 26 AGA infants born between the larger than or equal to 33th less than 37th week of gestation. In SGA infants significantly higher VLDL-cholesterol and triglyceride values were found than in AGA infants. In AGA infants less than 37 weeks of gestation total cholesterol, LDL-, and HDL-cholesterol concentrations were higher than in AGA infants larger than or equal to 37 weeks of gestation. In 10 betamethasone-treated AGA infants less than 37 weeks of gestation HDL-cholesterol was higher than in 16 untreated AGA infants less than 37 weeks of gestation."}
{"id": "PMID:194459", "title": "Infantile convulsions: transient infantile hypocalcemia associated with skeletal deformities.", "content": "An infant with skeletal deformities and hypocalcemic convulsions is described. The convulsions, which were first noted in the 5th week of life, as well as the low serum calcium level were transient. The skeletal deformities consited of deformation of the terminal phalanges of the right third finger and right second toe, syndactyly of the third and fourth finger of both hands and left pes equinovarus. X-ray examination revealed abnormal shape and structure of some bones of the hands. The most likely diagnosis is transient congenital idiopathic hypoparathyroidism, which has not yet been described in association with congenital skeletal anomalies.", "contents": "Infantile convulsions: transient infantile hypocalcemia associated with skeletal deformities. An infant with skeletal deformities and hypocalcemic convulsions is described. The convulsions, which were first noted in the 5th week of life, as well as the low serum calcium level were transient. The skeletal deformities consited of deformation of the terminal phalanges of the right third finger and right second toe, syndactyly of the third and fourth finger of both hands and left pes equinovarus. X-ray examination revealed abnormal shape and structure of some bones of the hands. The most likely diagnosis is transient congenital idiopathic hypoparathyroidism, which has not yet been described in association with congenital skeletal anomalies."}
{"id": "PMID:194461", "title": "Adaptation of neuromuscular junction to transmission of impulses after inactivation of acetylcholinesterase.", "content": "Adaptation of neuromuscular junction to transmission of impulses after inactivation of acetylcholinesterase. Acta Physiol. Pol., 1977, 28 (1): 23-30. Isolated preparation of rat diaphragm with phrenic nerve was incubated in paraoxon solutions which caused complete inactivation of acetylcholinesterase. This inactivation was associated with disturbances of neuromuscular transmission in the form of blockade of the tetanic response, post-tetanic inhibition of twitch responses and a decreased amplitude of the second response after the first one when two stimuli at a short interval were used. These disturbances were withdrawn somewhat during further incubation of the preparation, although it was kept in paraoxon solution which maintained complete inactivation of acetylcholinesterase. It is suggested that the observed recession of transmission disturbances may be caused by partial adaptation of blockade of the tetanic response, post-tetanic inhibition of twitch blockade of enzymatic hydrolysis of acetylcholine.", "contents": "Adaptation of neuromuscular junction to transmission of impulses after inactivation of acetylcholinesterase. Adaptation of neuromuscular junction to transmission of impulses after inactivation of acetylcholinesterase. Acta Physiol. Pol., 1977, 28 (1): 23-30. Isolated preparation of rat diaphragm with phrenic nerve was incubated in paraoxon solutions which caused complete inactivation of acetylcholinesterase. This inactivation was associated with disturbances of neuromuscular transmission in the form of blockade of the tetanic response, post-tetanic inhibition of twitch responses and a decreased amplitude of the second response after the first one when two stimuli at a short interval were used. These disturbances were withdrawn somewhat during further incubation of the preparation, although it was kept in paraoxon solution which maintained complete inactivation of acetylcholinesterase. It is suggested that the observed recession of transmission disturbances may be caused by partial adaptation of blockade of the tetanic response, post-tetanic inhibition of twitch blockade of enzymatic hydrolysis of acetylcholine."}
{"id": "PMID:194462", "title": "The effect of lipiodol injected into the pulmonary artery on blood pressure in pulmonary artery and thoracic aorta in dogs.", "content": "The effect of lipiodol injected into the pulmonary artery on blood pressure in pulmonary artery and thoracic aorta in dogs. Acta Physiol. Pol. 1977, 28 (2): 143--151. The purpose of the experiments, carried out on 10 anaesthetized dogs, was to trace changes in pressure in aorta and pulmonary artery within 2 hours after injection of lipiodol Ultra-Fluide into the pulmonary artery of dogs. In individual experiments a gradual fall, rise or maintenance of normal pressure was found in the aorta. Pressure changes in the pulmonary artery were similar. Statistical analysis failed to demonstrate any significant correlation between the pressure in the aorta or in the pulmonary artery and the time of measurements of these pressures during the two-hour experiment.", "contents": "The effect of lipiodol injected into the pulmonary artery on blood pressure in pulmonary artery and thoracic aorta in dogs. The effect of lipiodol injected into the pulmonary artery on blood pressure in pulmonary artery and thoracic aorta in dogs. Acta Physiol. Pol. 1977, 28 (2): 143--151. The purpose of the experiments, carried out on 10 anaesthetized dogs, was to trace changes in pressure in aorta and pulmonary artery within 2 hours after injection of lipiodol Ultra-Fluide into the pulmonary artery of dogs. In individual experiments a gradual fall, rise or maintenance of normal pressure was found in the aorta. Pressure changes in the pulmonary artery were similar. Statistical analysis failed to demonstrate any significant correlation between the pressure in the aorta or in the pulmonary artery and the time of measurements of these pressures during the two-hour experiment."}
{"id": "PMID:194469", "title": "X-ray analysis of enzymically purified elastin from bovine ligamentum nuchae.", "content": "Insoluble elastin has been isolated from bovine ligamentum nuchae by treatment with quanidine and dithiothreitol followed by digestion with collagenase, purified by affinity chromatography. The preparation was subjected to both wide- and low-angle X-ray analysis. The wide-angle diffraction patterns of relaxed and stretched specimens showed only two broad diffraction rings, corresponding to spacings of 4.5 and 9.3 A. No significant reflections were visible in the low-angle diffraction pattern of unstretched specimens, but on stretching an equatorial reflection was produced, corresponding to spacings of between 45 and 50 A.", "contents": "X-ray analysis of enzymically purified elastin from bovine ligamentum nuchae. Insoluble elastin has been isolated from bovine ligamentum nuchae by treatment with quanidine and dithiothreitol followed by digestion with collagenase, purified by affinity chromatography. The preparation was subjected to both wide- and low-angle X-ray analysis. The wide-angle diffraction patterns of relaxed and stretched specimens showed only two broad diffraction rings, corresponding to spacings of 4.5 and 9.3 A. No significant reflections were visible in the low-angle diffraction pattern of unstretched specimens, but on stretching an equatorial reflection was produced, corresponding to spacings of between 45 and 50 A."}
{"id": "PMID:194473", "title": "Myospherulosis. An electron-microscopic study of a human case.", "content": "An electronmicroscopic study of a human case of myospherulosis, which involved the nose and maxillary sinus, is reported. Large parent bodies limited by a thick electron-dense wall, enclosing variable numbers of spherules, were seen in cystic tissue spaces or adjacent connective tissue. Free spherules and shrunken degenerative forms were present as well. Similarity of these bodies to sporangium-like structures is suggested. The etiology of the disease remains unsettled.", "contents": "Myospherulosis. An electron-microscopic study of a human case. An electronmicroscopic study of a human case of myospherulosis, which involved the nose and maxillary sinus, is reported. Large parent bodies limited by a thick electron-dense wall, enclosing variable numbers of spherules, were seen in cystic tissue spaces or adjacent connective tissue. Free spherules and shrunken degenerative forms were present as well. Similarity of these bodies to sporangium-like structures is suggested. The etiology of the disease remains unsettled."}
{"id": "PMID:194475", "title": "A case of cerebral gigantism and hepatocarcinoma.", "content": "A 14-year-old boy, who had the physical and neurological characteristics of cerebral gigantism (Sotos syndrome), developed hepatocarcinoma. This tumor is rare in children and has never, to our knowledge, been recorded in a patient with cerebral gigantism. An autopsy was performed, the first we are aware of in a patient with cerebral gigantism without increased size in ventricles.", "contents": "A case of cerebral gigantism and hepatocarcinoma. A 14-year-old boy, who had the physical and neurological characteristics of cerebral gigantism (Sotos syndrome), developed hepatocarcinoma. This tumor is rare in children and has never, to our knowledge, been recorded in a patient with cerebral gigantism. An autopsy was performed, the first we are aware of in a patient with cerebral gigantism without increased size in ventricles."}
{"id": "PMID:194476", "title": "Prevention or modification of varicella using zoster immune plasma.", "content": "Zoster immune plasma (ZIP) was given to 31 susceptible immunocompromised children one to seven days (median, two days) following household, playmate, or hospital exposures to varicella. The average amount of ZIP transfused was 7 ml/kg. Twenty-one children did not develop varicella or persistent antibodies to varicella-zoster virus (VZV). Eight (26%) of the 31 contracted clinical varicella. Seven cases were mild, but in one child, who was given ZIP seven days after exposure, visceral disease developed and the child died. Two children had subclinical varicella that was documented by persistence of VZV antibodies for at least ten months after passive immunization. Because none of the 30 children given ZIP one to six days following exposure had severe varicella, we conclude that ZIP is effective in preventing or modifying varicella in immunocompromised patients if given shortly after exposure.", "contents": "Prevention or modification of varicella using zoster immune plasma. Zoster immune plasma (ZIP) was given to 31 susceptible immunocompromised children one to seven days (median, two days) following household, playmate, or hospital exposures to varicella. The average amount of ZIP transfused was 7 ml/kg. Twenty-one children did not develop varicella or persistent antibodies to varicella-zoster virus (VZV). Eight (26%) of the 31 contracted clinical varicella. Seven cases were mild, but in one child, who was given ZIP seven days after exposure, visceral disease developed and the child died. Two children had subclinical varicella that was documented by persistence of VZV antibodies for at least ten months after passive immunization. Because none of the 30 children given ZIP one to six days following exposure had severe varicella, we conclude that ZIP is effective in preventing or modifying varicella in immunocompromised patients if given shortly after exposure."}
{"id": "PMID:194477", "title": "SV40 T-antigen expression in skin fibroblasts from clinically normal individuals and from ten cases of Fanconi anemia.", "content": "Previous studies of the expression of SV40 genetic information by skin fibroblasts included limited numbers of cell donors and failed to adequately consider possible effects of age, sex, and ethnic origin on assay results. A population of 76 healthy subjects were selected for study following determination of personal and family disease history and karyological analysis. Skin fibroblasts from these individuals were tested for expression of SV40 T-antigen by indirect immunofluorescent assay. The data were normally distributed and showed no significant differences between the age, sex, or ethnic groups tested. The occurrence of rare karyological anomalies in this control population had no effect on T-antigen expression. Fibroblasts from 10 Fanconi anemia patients demonstrated significantly elevated expression of T antigen compared to the well-defined control population, based on simple statistical criteria. T-antigen expression was elevated in two young patients prior to the onset of anemia and did not appear to correlate with the incidence or severity of other specific symptoms. Thus, elevated T-antigen expression in Fanconi anemia fibroblasts reflects an actual defect at the cellular level, rather than clinical, age, sex or ethnic factors not previously considered.", "contents": "SV40 T-antigen expression in skin fibroblasts from clinically normal individuals and from ten cases of Fanconi anemia. Previous studies of the expression of SV40 genetic information by skin fibroblasts included limited numbers of cell donors and failed to adequately consider possible effects of age, sex, and ethnic origin on assay results. A population of 76 healthy subjects were selected for study following determination of personal and family disease history and karyological analysis. Skin fibroblasts from these individuals were tested for expression of SV40 T-antigen by indirect immunofluorescent assay. The data were normally distributed and showed no significant differences between the age, sex, or ethnic groups tested. The occurrence of rare karyological anomalies in this control population had no effect on T-antigen expression. Fibroblasts from 10 Fanconi anemia patients demonstrated significantly elevated expression of T antigen compared to the well-defined control population, based on simple statistical criteria. T-antigen expression was elevated in two young patients prior to the onset of anemia and did not appear to correlate with the incidence or severity of other specific symptoms. Thus, elevated T-antigen expression in Fanconi anemia fibroblasts reflects an actual defect at the cellular level, rather than clinical, age, sex or ethnic factors not previously considered."}
{"id": "PMID:194478", "title": "The Philadelphia variant of galactokinase.", "content": "We have previously reported the existence of a polymorphism that causes black populations to have lower mean RBC galactokinase activity than comparable white populations. We have designated this allele the Philadelphia variant, GALKP, and have suggested that it is common in blacks and rare in whites. GALKP individuals have normal WBC GALK activity, in contrast to the half normal WBC GALK activities of heterozygotes for the allele (GALKG) that causes the galactokinase-deficient form of galactosemia. In one family, we have presented evidence for the existence of two sisters heterozygous for both GALKG and GALKP alleles. These individuals have 50% normal WBC GALK activity and less than 50% normal red cell activity. The latter finding indicates that the two variant GALK alleles additively affect RBC activity. The WBC results suggest that the low activity of GALK in RBC of individuals with the GALKP allele is due to its relative instability. We could obtain no evidence for such instability from studies of high reticulocyte bloods or RBC fractionation. Furthermore, we could not demonstrate that the GALK in WBC from GALKP individuals has altered electrophoretic migration.", "contents": "The Philadelphia variant of galactokinase. We have previously reported the existence of a polymorphism that causes black populations to have lower mean RBC galactokinase activity than comparable white populations. We have designated this allele the Philadelphia variant, GALKP, and have suggested that it is common in blacks and rare in whites. GALKP individuals have normal WBC GALK activity, in contrast to the half normal WBC GALK activities of heterozygotes for the allele (GALKG) that causes the galactokinase-deficient form of galactosemia. In one family, we have presented evidence for the existence of two sisters heterozygous for both GALKG and GALKP alleles. These individuals have 50% normal WBC GALK activity and less than 50% normal red cell activity. The latter finding indicates that the two variant GALK alleles additively affect RBC activity. The WBC results suggest that the low activity of GALK in RBC of individuals with the GALKP allele is due to its relative instability. We could obtain no evidence for such instability from studies of high reticulocyte bloods or RBC fractionation. Furthermore, we could not demonstrate that the GALK in WBC from GALKP individuals has altered electrophoretic migration."}
{"id": "PMID:194480", "title": "Clinical and laboratory correlates of molar pregnancy and trophoblastic disease.", "content": "From January 1, 1970 to July 1, 1976, 128 women had hydatidiform moles evacuated at the Los Angeles County-University of Southern California Women's Hospitals. Of the 121 patients with follow-up, persistent trophoblastic disease (TD) was diagnosed in 32 (26.4 per cent). Remission was achieved in all treated patients. The frequency of TD was significantly increased in pregnancies large for dates (47.8 per cent), with a uterus greater than 20 weeks' gestational size (45.0 per cent) or with theca-lutein cysts greater than 5 cm. in diameter (50.0 per cent). A normal regression curve for serum beta-human gonadotropin as measured by radioimmunoassay has been constructed as an aid to the early recognition of postmolar TD (invasive mole and choriocarcinoma).", "contents": "Clinical and laboratory correlates of molar pregnancy and trophoblastic disease. From January 1, 1970 to July 1, 1976, 128 women had hydatidiform moles evacuated at the Los Angeles County-University of Southern California Women's Hospitals. Of the 121 patients with follow-up, persistent trophoblastic disease (TD) was diagnosed in 32 (26.4 per cent). Remission was achieved in all treated patients. The frequency of TD was significantly increased in pregnancies large for dates (47.8 per cent), with a uterus greater than 20 weeks' gestational size (45.0 per cent) or with theca-lutein cysts greater than 5 cm. in diameter (50.0 per cent). A normal regression curve for serum beta-human gonadotropin as measured by radioimmunoassay has been constructed as an aid to the early recognition of postmolar TD (invasive mole and choriocarcinoma)."}
{"id": "PMID:194482", "title": "Immunosuppression and eye disease. First Vail lecture.", "content": "Several viral, fungal, and protozoal diseases of the eye are significantly associated with immunologic deficiencies. Of the viral agents, cytomegaly and herpes simplex and zoster cause a discrete necrotizing retinopathy that has the characteristics of vascular occlusion. Measles may result in a delayed retinopathy that is predominantly macular and associated with subacute progressive encephalopathy. Of the fungal agents, Candida and Aspergillus are apt to involve the eye, beginning as choroidal lesions with extension forward to involve the pigment epithelium and retina secondarily. Mucor and Cryptococcus are less common. Toxoplasmosis is the one ocular protozoal disease whose incidence is increased by immunosuppression, and, like the viral diseases, is characterized by a discrete necrotizing retinopathy and probably results from activation of dormant organisms in the retina. Autoimmunity undoubtedly plays an important role in eye disease but its ocular pathogenesis is obscure.", "contents": "Immunosuppression and eye disease. First Vail lecture. Several viral, fungal, and protozoal diseases of the eye are significantly associated with immunologic deficiencies. Of the viral agents, cytomegaly and herpes simplex and zoster cause a discrete necrotizing retinopathy that has the characteristics of vascular occlusion. Measles may result in a delayed retinopathy that is predominantly macular and associated with subacute progressive encephalopathy. Of the fungal agents, Candida and Aspergillus are apt to involve the eye, beginning as choroidal lesions with extension forward to involve the pigment epithelium and retina secondarily. Mucor and Cryptococcus are less common. Toxoplasmosis is the one ocular protozoal disease whose incidence is increased by immunosuppression, and, like the viral diseases, is characterized by a discrete necrotizing retinopathy and probably results from activation of dormant organisms in the retina. Autoimmunity undoubtedly plays an important role in eye disease but its ocular pathogenesis is obscure."}
{"id": "PMID:194479", "title": "Cutaneous dissemination of herpes simplex virus in individuals fifteen years of age and older.", "content": "We have reported the case histories of two individuals with underlying atopic dermatitis who developed extensive vesicular eruptions. In both cases herpes simplex virus type l was isolated from skin lesions and both individuals ultimately recovered. These two cases represent only the third and fourth instances of this syndrome proven to be caused by herpes simplex virus type l that have been reported in older individuals. In addition we have reviewed the literature relative to cutaneous disseminated herpes simplex virus infections occurring in individuals over the age of 15 and have presented a comprehensive overview of this disease.", "contents": "Cutaneous dissemination of herpes simplex virus in individuals fifteen years of age and older. We have reported the case histories of two individuals with underlying atopic dermatitis who developed extensive vesicular eruptions. In both cases herpes simplex virus type l was isolated from skin lesions and both individuals ultimately recovered. These two cases represent only the third and fourth instances of this syndrome proven to be caused by herpes simplex virus type l that have been reported in older individuals. In addition we have reviewed the literature relative to cutaneous disseminated herpes simplex virus infections occurring in individuals over the age of 15 and have presented a comprehensive overview of this disease."}
{"id": "PMID:194483", "title": "Assessment of physical maturation and somatomedin levels during puberty.", "content": "The chronologic age, skeletal age, and somatomedin level of thirty-nine Caucasian girls of various developmental stages were compared. The results showed that there was a significant difference between the somatomedin levels in the plasma of circumpubertal and postpubertal females. No significant difference was noted between the prepubertal and the circumpubertal subjects tested. In addition, the skeletal age appears to be a better indicator of physical maturation than does the chronologic age of an individual. In order to substantiate the concept of somatomedin as a true marker for the pubertal growth spurt, this study should be continued on a longitudinal basis utilizing rate-of-growth data.", "contents": "Assessment of physical maturation and somatomedin levels during puberty. The chronologic age, skeletal age, and somatomedin level of thirty-nine Caucasian girls of various developmental stages were compared. The results showed that there was a significant difference between the somatomedin levels in the plasma of circumpubertal and postpubertal females. No significant difference was noted between the prepubertal and the circumpubertal subjects tested. In addition, the skeletal age appears to be a better indicator of physical maturation than does the chronologic age of an individual. In order to substantiate the concept of somatomedin as a true marker for the pubertal growth spurt, this study should be continued on a longitudinal basis utilizing rate-of-growth data."}
{"id": "PMID:194484", "title": "Effect of dichloromethane diphosphonate on calcium homeostatic mechanisms in pregnant cows.", "content": "The administration of 4 mg/kg/day of dichloromethane diphosphonate (Cl2MDP) subcutaneously to pregnant cows fed a low-calcium diet significantly reduced bone resorption as indicated by microradiographic evaluation of endosteal surfaces of cross sections of ribs. Plasma parathyroid hormone levels were similar between Cl2MDP-treated and control cows prepartum, during EDTA infusions, and near parturition. Ultrastructurally, chief cells of the parathyroid glands of both groups of cows were in the active stage of the secretory cycle. The chronically stimulated chief cell from cows administered Cl2MDP had a large cytoplasmic area containing many lipofuscin granules and lysosomal bodies and a few secretory granules near the large Golgi apparatus or aligned along the plasma membrane. Uptake of calcium 45 by the duodenal mucosa incubated in vitro was greater in Cl2MDP-treated cows compared to control cows. The administration of Cl2MDP significantly reduced rapidly mobilization calcium reserves. Following an intravenous EDTA infusion and the spontaneous calcium drain associated with parturition and the beginning of lactation, Cl2MDP-treated cows developed severe hypocalcemia. The rapid mobilization of calcium reserves in cows administered Cl2MDP prepartum was impaired mainly because of diminished resorption of bone despite adequate parathyroid hormone secretion in response to severe postpartal or EDTA-induced hypocalcemia.", "contents": "Effect of dichloromethane diphosphonate on calcium homeostatic mechanisms in pregnant cows. The administration of 4 mg/kg/day of dichloromethane diphosphonate (Cl2MDP) subcutaneously to pregnant cows fed a low-calcium diet significantly reduced bone resorption as indicated by microradiographic evaluation of endosteal surfaces of cross sections of ribs. Plasma parathyroid hormone levels were similar between Cl2MDP-treated and control cows prepartum, during EDTA infusions, and near parturition. Ultrastructurally, chief cells of the parathyroid glands of both groups of cows were in the active stage of the secretory cycle. The chronically stimulated chief cell from cows administered Cl2MDP had a large cytoplasmic area containing many lipofuscin granules and lysosomal bodies and a few secretory granules near the large Golgi apparatus or aligned along the plasma membrane. Uptake of calcium 45 by the duodenal mucosa incubated in vitro was greater in Cl2MDP-treated cows compared to control cows. The administration of Cl2MDP significantly reduced rapidly mobilization calcium reserves. Following an intravenous EDTA infusion and the spontaneous calcium drain associated with parturition and the beginning of lactation, Cl2MDP-treated cows developed severe hypocalcemia. The rapid mobilization of calcium reserves in cows administered Cl2MDP prepartum was impaired mainly because of diminished resorption of bone despite adequate parathyroid hormone secretion in response to severe postpartal or EDTA-induced hypocalcemia."}
{"id": "PMID:194485", "title": "Virus-induced lysosomal enzyme dissolution of nasal turbinate cartilage.", "content": "The mechanism of laryngotracheitis virus-induced dissolution of chick nasal turbinate cartilage was studied by lysosomal enzyme histochemistry. Five-day-old chicks were infected by intranasal instillation, and changes in lysosomal enzyme distribution were followed at daily intervals through the tissue regeneration stage, Day 28. In the mucosa the lysosomes were activated beginning on Day 1, and glycerol acid phosphatase and a diffuse form of beta-glucuronidase were released concomitant with tissue cell destruction. In the chondrocytes (where glycerol acid phosphatase was absent), beginning on Day 2, particulate (lysosomal) beta-glucuronidase decreased as diffuse beta-glucuronidase increased and extended out into the matrix. The cartilage lost its metachromatic staining properties and became soft and pliable. Regeneration of the mucosa started on Day 6 and gradual reappearance of metachromatic staining of the cartilage began on Day 8 with considerable recovery of original turbinate structure by Day 12. A lysosomal membrane labilizer, vitamin A, exacerbated the cartilage pathology, whereas a stabilizer, cortisone, retarded it.", "contents": "Virus-induced lysosomal enzyme dissolution of nasal turbinate cartilage. The mechanism of laryngotracheitis virus-induced dissolution of chick nasal turbinate cartilage was studied by lysosomal enzyme histochemistry. Five-day-old chicks were infected by intranasal instillation, and changes in lysosomal enzyme distribution were followed at daily intervals through the tissue regeneration stage, Day 28. In the mucosa the lysosomes were activated beginning on Day 1, and glycerol acid phosphatase and a diffuse form of beta-glucuronidase were released concomitant with tissue cell destruction. In the chondrocytes (where glycerol acid phosphatase was absent), beginning on Day 2, particulate (lysosomal) beta-glucuronidase decreased as diffuse beta-glucuronidase increased and extended out into the matrix. The cartilage lost its metachromatic staining properties and became soft and pliable. Regeneration of the mucosa started on Day 6 and gradual reappearance of metachromatic staining of the cartilage began on Day 8 with considerable recovery of original turbinate structure by Day 12. A lysosomal membrane labilizer, vitamin A, exacerbated the cartilage pathology, whereas a stabilizer, cortisone, retarded it."}
{"id": "PMID:194487", "title": "An examination of the federal psychiatric training grant peer review process.", "content": "The authors present some of the criticisms that have been leveled against the federal peer review system of approving or disapproving monetary grants. They then summarize the process used by the National Institute of Mental Health's Psychiatry Education Branch to judge grant applications, focusing on the disposition of 527 applications reviewed in November 1974-January 1975. They found that the wide distribution of the reviewers by geography, subspecialty, experience, sex, and ethnicity, plus the steps taken to guard against bias and ensure fairness, were effective, refuting many of the criticisms of the group peer review process.", "contents": "An examination of the federal psychiatric training grant peer review process. The authors present some of the criticisms that have been leveled against the federal peer review system of approving or disapproving monetary grants. They then summarize the process used by the National Institute of Mental Health's Psychiatry Education Branch to judge grant applications, focusing on the disposition of 527 applications reviewed in November 1974-January 1975. They found that the wide distribution of the reviewers by geography, subspecialty, experience, sex, and ethnicity, plus the steps taken to guard against bias and ensure fairness, were effective, refuting many of the criticisms of the group peer review process."}
{"id": "PMID:194490", "title": "Definition of the antigenic pattern of Entamoeba histolytica, and immunoelectrophoretic analysis of the variation of patient response to amebic disease.", "content": "The antigenic anatomy of Entamoeba histolytica and the variation in response of 148 patients with amebic disease are described. Immunoelectrophoretic patterns and indirect hemagglutination titers were studied in sera obtained from patients with amebic disease acquired in several areas of the world, i.e. Canada, Vietnam, Afric, India, Central America, and southern United States. The various populations are compared and similarities and differences are discussed.", "contents": "Definition of the antigenic pattern of Entamoeba histolytica, and immunoelectrophoretic analysis of the variation of patient response to amebic disease. The antigenic anatomy of Entamoeba histolytica and the variation in response of 148 patients with amebic disease are described. Immunoelectrophoretic patterns and indirect hemagglutination titers were studied in sera obtained from patients with amebic disease acquired in several areas of the world, i.e. Canada, Vietnam, Afric, India, Central America, and southern United States. The various populations are compared and similarities and differences are discussed."}
{"id": "PMID:194491", "title": "Experimental amebiasis. I. Pathogenicity of axenically cultured Entamoeba histolytica in the brain of the newborn mouse.", "content": "Axenically cultured Entamoeba histolytica inoculated intracerebrally into newborn Swiss mice invaded the cerebrum and produced multiple abscesses containing viable trophozoites. As few as 20 amebae of a virulent strain (HM-1:IMSS) occasionally produced fatal disease, 200 killed about 75% of animals and higher doses regularly killed all animals. In contrast, avirulent strains (HK-9 and HB-301:NIH) failed to produce acute brain disease in comparable time periods even when mice were inoculated with as many as 20,000 amebae. Two other strains (1295 and H-458:CDC) were of intermediate virulence. High doses of avirulent amebae often produced hydrocephalus as a late manifestation. In newborn, 3 week-old, and 6-week-old mice resistance to infection increased with age, and older animals often responded late to virulent strains by developing hydrocephalus.", "contents": "Experimental amebiasis. I. Pathogenicity of axenically cultured Entamoeba histolytica in the brain of the newborn mouse. Axenically cultured Entamoeba histolytica inoculated intracerebrally into newborn Swiss mice invaded the cerebrum and produced multiple abscesses containing viable trophozoites. As few as 20 amebae of a virulent strain (HM-1:IMSS) occasionally produced fatal disease, 200 killed about 75% of animals and higher doses regularly killed all animals. In contrast, avirulent strains (HK-9 and HB-301:NIH) failed to produce acute brain disease in comparable time periods even when mice were inoculated with as many as 20,000 amebae. Two other strains (1295 and H-458:CDC) were of intermediate virulence. High doses of avirulent amebae often produced hydrocephalus as a late manifestation. In newborn, 3 week-old, and 6-week-old mice resistance to infection increased with age, and older animals often responded late to virulent strains by developing hydrocephalus."}
{"id": "PMID:194492", "title": "Experimental amebiasis. II. Hepatic amebiasis in the newborn hamster.", "content": "Newborn hamsters inoculated intrahepatically were highly susceptible to infection by axenically cultured Entamoeba histolytica. Inoculations were performed through the abdominal wall, and lesions could be observed through the skin as early as 4 days after inoculation. The most virulent amebal strain, HM-1:IMSS, produced liver lesions in 19% of newborn animals inoculated with 20 amebae, and in about 90% receiving 2,000 amebae. Eleven other strains similarly tested either produced no lesions with 20,000 amebae or were of intermediate virulence. Two hamster strains did not show appreciable differences in susceptibility to the HM-1:IMSS amebal strain. Newborn hamsters were more susceptible to HM-1:IMSS amebae than animals which were 2, 4, or 7 days old at the time of inoculation. Three-week-old animals were resistant to doses below 20,000 virulent amebae.", "contents": "Experimental amebiasis. II. Hepatic amebiasis in the newborn hamster. Newborn hamsters inoculated intrahepatically were highly susceptible to infection by axenically cultured Entamoeba histolytica. Inoculations were performed through the abdominal wall, and lesions could be observed through the skin as early as 4 days after inoculation. The most virulent amebal strain, HM-1:IMSS, produced liver lesions in 19% of newborn animals inoculated with 20 amebae, and in about 90% receiving 2,000 amebae. Eleven other strains similarly tested either produced no lesions with 20,000 amebae or were of intermediate virulence. Two hamster strains did not show appreciable differences in susceptibility to the HM-1:IMSS amebal strain. Newborn hamsters were more susceptible to HM-1:IMSS amebae than animals which were 2, 4, or 7 days old at the time of inoculation. Three-week-old animals were resistant to doses below 20,000 virulent amebae."}
{"id": "PMID:194493", "title": "Vascular exclusion in surgery of the liver: experimental basis, technic, and clinical results.", "content": "Because liver exeresis and surgery for liver trauma still carry  a great mortality by hemorrhage or air embolism due to suprahepatic or vena cava  injuries, temporary vascular exclusion of the liver is considered. Based on hemodynamic, biologic, and anatomopathologic experimental and clinical data, a catheter was designed that allows isolation of the retro-and suprahepatic portions of the inferior vena cava and consequently vascular exclusion of the liver for 30 minutes. We report on seven patients in whom this technic was utilized (4 requiring hepatectomy and 3 traumatized), confirming the utility, ease, and efficacy of this method.", "contents": "Vascular exclusion in surgery of the liver: experimental basis, technic, and clinical results. Because liver exeresis and surgery for liver trauma still carry  a great mortality by hemorrhage or air embolism due to suprahepatic or vena cava  injuries, temporary vascular exclusion of the liver is considered. Based on hemodynamic, biologic, and anatomopathologic experimental and clinical data, a catheter was designed that allows isolation of the retro-and suprahepatic portions of the inferior vena cava and consequently vascular exclusion of the liver for 30 minutes. We report on seven patients in whom this technic was utilized (4 requiring hepatectomy and 3 traumatized), confirming the utility, ease, and efficacy of this method."}
{"id": "PMID:194494", "title": "Prognosis and treatment in minimal breast cancer.", "content": "Of 176 patients with minimal breast cancer, 138 had intraductal carcinoma in situ, 21 minimally invasive carcinoma, and 17 lobular carcinoma in situ. Various modalities of treatment were used including radical, modified radical, and simple mastectomy with and without radiation therapy. Long-term postoperative follow-up was available in all but five patients and ranged from one year to twenty-one years. Actuarial analysis projected a twenty year survival of 93.2 per cent for the entire group. Analysis of survival figures based on each of the several treatment modalities showed no definite advantage of one form of treatment over another. The data suggest that minimal breast cancer is a prognostically favorable diagnosis, provided invasive carcinoma is not present or does not develop in the opposite breast. It is also indicated that breast cancer is potentially a bilateral disease and that follow-up and treatment of the opposite breast must be of major concern in the care of these patients.", "contents": "Prognosis and treatment in minimal breast cancer. Of 176 patients with minimal breast cancer, 138 had intraductal carcinoma in situ, 21 minimally invasive carcinoma, and 17 lobular carcinoma in situ. Various modalities of treatment were used including radical, modified radical, and simple mastectomy with and without radiation therapy. Long-term postoperative follow-up was available in all but five patients and ranged from one year to twenty-one years. Actuarial analysis projected a twenty year survival of 93.2 per cent for the entire group. Analysis of survival figures based on each of the several treatment modalities showed no definite advantage of one form of treatment over another. The data suggest that minimal breast cancer is a prognostically favorable diagnosis, provided invasive carcinoma is not present or does not develop in the opposite breast. It is also indicated that breast cancer is potentially a bilateral disease and that follow-up and treatment of the opposite breast must be of major concern in the care of these patients."}
{"id": "PMID:194495", "title": "Evidence for the involvement of microtubules in wound contraction.", "content": "Many theories have been proposed for the mechanism of wound contraction, that phenomenon of wound closure in which the skin surrounding the tissue defect is drawn into the open wound. When agents that inhibit microtubular function, such as vinblastine and colchicine, were topically applied to actively contracting wounds, contraction stopped. Cytochalasin B, an agent that reportedly disrupts microfilaments, did not alter contraction. These results suggest that wound contraction is related to the functioning of microtubules in fibroblasts within the wound and is proceeding at its maximal rate. The results tend not to support the theory that the microfilament components of cells are involved in wound contraction.", "contents": "Evidence for the involvement of microtubules in wound contraction. Many theories have been proposed for the mechanism of wound contraction, that phenomenon of wound closure in which the skin surrounding the tissue defect is drawn into the open wound. When agents that inhibit microtubular function, such as vinblastine and colchicine, were topically applied to actively contracting wounds, contraction stopped. Cytochalasin B, an agent that reportedly disrupts microfilaments, did not alter contraction. These results suggest that wound contraction is related to the functioning of microtubules in fibroblasts within the wound and is proceeding at its maximal rate. The results tend not to support the theory that the microfilament components of cells are involved in wound contraction."}
{"id": "PMID:194497", "title": "Recovery of neuromuscular transmission following desensitization block.", "content": "Depolarization and desensitization neuromuscular blockade was induced with suxamethonium. Rate of recovery of neuromuscular transmission did not vary with the nature of the blockade.", "contents": "Recovery of neuromuscular transmission following desensitization block. Depolarization and desensitization neuromuscular blockade was induced with suxamethonium. Rate of recovery of neuromuscular transmission did not vary with the nature of the blockade."}
{"id": "PMID:194496", "title": "Effect of cytosine arabinoside on Herpes virus infection in renal allograft recipients.", "content": "Cytosine arabinoside (Ara-C) was used for treatment of severe symptomatic cytomegalovirus (CMV)-herpes infections that were seen in nineteen of 174 renal allograft recipients. Ara-C was administered by continuous intravenous infusion at a mean dose of 35 mg/m2 daily for three to four days. Side effects were few and minor in nature. All cases of herpes simplex and herpes zoster, which usually have a prolonged and sometimes unfavorable course in immunosuppressed patients, cleared promptly with no recurrence. All nine patients, except one who had CMV infection with the symptom complex of fever and retinitis or pneumonitis, responded satisfactorily. In the three patients in whom the CMV titers were available, there was a significant decrease in titer within two weeks after treatment. This pilot study of Ara-C in treatment of CMV-herpes infections in immunosuppressed renal allograft recipients suggests a degree of efficacy and safety in the drug that would justify a carefully designed, controlled study.", "contents": "Effect of cytosine arabinoside on Herpes virus infection in renal allograft recipients. Cytosine arabinoside (Ara-C) was used for treatment of severe symptomatic cytomegalovirus (CMV)-herpes infections that were seen in nineteen of 174 renal allograft recipients. Ara-C was administered by continuous intravenous infusion at a mean dose of 35 mg/m2 daily for three to four days. Side effects were few and minor in nature. All cases of herpes simplex and herpes zoster, which usually have a prolonged and sometimes unfavorable course in immunosuppressed patients, cleared promptly with no recurrence. All nine patients, except one who had CMV infection with the symptom complex of fever and retinitis or pneumonitis, responded satisfactorily. In the three patients in whom the CMV titers were available, there was a significant decrease in titer within two weeks after treatment. This pilot study of Ara-C in treatment of CMV-herpes infections in immunosuppressed renal allograft recipients suggests a degree of efficacy and safety in the drug that would justify a carefully designed, controlled study."}
{"id": "PMID:194503", "title": "Investigations on the turnover of adrenocortical mitochondria. VI. An autoradiographic study of the effect of ACTH on the radioactivity decay in the mitochondrial compartment from the zona fasciculata of 3H-thymidine injected rats.", "content": "The radioactivity decay of the mitochondrial compartment from the zona fasciculata of the adrenal cortex of 3H-thymidine-injected rats was followed by high resolution autoradiography. The number of days in which the radioactivity of the mitochondrial compartment was reduced to a half was calculated from the semilogarithmic plots of radioactivity versus time. Since DNA is a very stable molecule, it was assumed that this parameter can be an estimate of the half-life of adrenocortical mitochondria. The half-life of mitochondria from the zona fasciculata of the normal rat averaged 11.17 days, and ACTH was found to increase significantly this figure to about 15 days. It is hypothesized that the ACTH-elicited stimulation of the growth of rat adrenal zona fasciculata mitochondria involves not only hypertrophy and proliferation of the organelles (Nussdorfer et al., '74b), but also the slowing down of the degeneration rate of mitochondria.", "contents": "Investigations on the turnover of adrenocortical mitochondria. VI. An autoradiographic study of the effect of ACTH on the radioactivity decay in the mitochondrial compartment from the zona fasciculata of 3H-thymidine injected rats. The radioactivity decay of the mitochondrial compartment from the zona fasciculata of the adrenal cortex of 3H-thymidine-injected rats was followed by high resolution autoradiography. The number of days in which the radioactivity of the mitochondrial compartment was reduced to a half was calculated from the semilogarithmic plots of radioactivity versus time. Since DNA is a very stable molecule, it was assumed that this parameter can be an estimate of the half-life of adrenocortical mitochondria. The half-life of mitochondria from the zona fasciculata of the normal rat averaged 11.17 days, and ACTH was found to increase significantly this figure to about 15 days. It is hypothesized that the ACTH-elicited stimulation of the growth of rat adrenal zona fasciculata mitochondria involves not only hypertrophy and proliferation of the organelles (Nussdorfer et al., '74b), but also the slowing down of the degeneration rate of mitochondria."}
{"id": "PMID:194506", "title": "Effect of isometric handgrip on systolic time intervals in patients with ischemic heart disease and cyclic amp phosphodiesterase inhibitor pretreatment.", "content": "The effect of cAMP phosphodiesterase inhibitor EG626 on the left ventricular function was studied in 23 patients with ischemic heart disease at rest and during the IHG test. Administration of a single dose of the substance produced changes in STIs indicating an increase in cardiac output and a possible enhancement of myocardial contractility during the IHG test. EG626 may have a beneficial effect on impaired left ventricular function in patients with ischemic heart disease.", "contents": "Effect of isometric handgrip on systolic time intervals in patients with ischemic heart disease and cyclic amp phosphodiesterase inhibitor pretreatment. The effect of cAMP phosphodiesterase inhibitor EG626 on the left ventricular function was studied in 23 patients with ischemic heart disease at rest and during the IHG test. Administration of a single dose of the substance produced changes in STIs indicating an increase in cardiac output and a possible enhancement of myocardial contractility during the IHG test. EG626 may have a beneficial effect on impaired left ventricular function in patients with ischemic heart disease."}
{"id": "PMID:194504", "title": "Comparative neuromuscular effects of lincomycin and clindamycin.", "content": "The effects of lincomycin and clindamycin on neuromuscular transmission in vitro were studied. Standard microelectrode technics were used to measure miniature endplate potential (MEPP) amplitude and frequency, and endplate sensitivity to acetycholine on the frog sartorius muscle. Twitch tension and nerve terminal acetycholine release were also studied. In the drug concentration range where twitch tension changes occurred, both drugs caused marked decreases in MEPP amplitude and decreases in endplate sensitivity to iontophoretically applied acetylcholine. Lincomycin did not alter MEPP frequency but decreased acetylcholine release. Clindamycin increased MEPP frequency and increased acetylcholine release. The study shows that both lincomycin and clindamycin cause blockade of neuromuscular transmission through a postsynaptic action. However, at high concentrations, lincomycin has a nerve-terminal depressant effect, while clindamycin has a marked presynaptic stimulatory effect.", "contents": "Comparative neuromuscular effects of lincomycin and clindamycin. The effects of lincomycin and clindamycin on neuromuscular transmission in vitro were studied. Standard microelectrode technics were used to measure miniature endplate potential (MEPP) amplitude and frequency, and endplate sensitivity to acetycholine on the frog sartorius muscle. Twitch tension and nerve terminal acetycholine release were also studied. In the drug concentration range where twitch tension changes occurred, both drugs caused marked decreases in MEPP amplitude and decreases in endplate sensitivity to iontophoretically applied acetylcholine. Lincomycin did not alter MEPP frequency but decreased acetylcholine release. Clindamycin increased MEPP frequency and increased acetylcholine release. The study shows that both lincomycin and clindamycin cause blockade of neuromuscular transmission through a postsynaptic action. However, at high concentrations, lincomycin has a nerve-terminal depressant effect, while clindamycin has a marked presynaptic stimulatory effect."}
{"id": "PMID:194505", "title": "Neuromuscular block by antibiotics: polymyxin B.", "content": "Characteristics of neuromuscular block produced by polymyxin B (PXB) were examined in 12 anesthetized cats, using sciatic nervetibialis anticus muscle preparations. The ED50 was 6.7 (+/- 1.4, SD) PXB base/kg body weight. The ED95 was 10.8 (+/- 2.4) mg/kg. Spontaneous recovery from 25 percent of control to 75 percent of control required 72 (+/- 16) minutes. During a 50 percent block, train-of-four twitches elicited at 2 Hz faded with a train-of-four ratio of 0.42 (+/- 0.13), but the tetanus did not fade. Edrophonium Cl, neostigmine methylsulfate, and pyridostigmine Br at sub-clinical dosages weakly antagonized the block but enhanced the block at anti-curare dosages. All 3 cholinesterase inhibitors were short acting, lasting 10 to 15 minutes, and noncumulative on repeated injection. The potency ratio was approximately 20:10:1 in the order of edrophonium, neostigmine, and pyridostigmine on a weight-for-weight basis. Calcium partially antagonized the block. The authors conclude that neuromuscular blocks produced by various antibiotics differ from each other and from that produced by other groups of neuromuscular blocking agents, including curare.", "contents": "Neuromuscular block by antibiotics: polymyxin B. Characteristics of neuromuscular block produced by polymyxin B (PXB) were examined in 12 anesthetized cats, using sciatic nervetibialis anticus muscle preparations. The ED50 was 6.7 (+/- 1.4, SD) PXB base/kg body weight. The ED95 was 10.8 (+/- 2.4) mg/kg. Spontaneous recovery from 25 percent of control to 75 percent of control required 72 (+/- 16) minutes. During a 50 percent block, train-of-four twitches elicited at 2 Hz faded with a train-of-four ratio of 0.42 (+/- 0.13), but the tetanus did not fade. Edrophonium Cl, neostigmine methylsulfate, and pyridostigmine Br at sub-clinical dosages weakly antagonized the block but enhanced the block at anti-curare dosages. All 3 cholinesterase inhibitors were short acting, lasting 10 to 15 minutes, and noncumulative on repeated injection. The potency ratio was approximately 20:10:1 in the order of edrophonium, neostigmine, and pyridostigmine on a weight-for-weight basis. Calcium partially antagonized the block. The authors conclude that neuromuscular blocks produced by various antibiotics differ from each other and from that produced by other groups of neuromuscular blocking agents, including curare."}
{"id": "PMID:194513", "title": "Discussion paper: dual effects of tumor antigens: induction of tumor resistance or tumor growth enhancement.", "content": "TA3-HA nonspecific tumors growing in ascites form shed their membrane components into the ascites fluid. This product can induce tumor growth enhancement if given together with or after i.p. tumor inoculation in relatively large quantities, but if given i.m. in small quantities, several days before tumor challenge, the mice show an elevated resistance to the tumor. The strictly strain-specific TA3-St line does not release such membrane components into the ascites fluid. It has also been found that the TA3-HA cells have a larger membrane fluidity than the TA3-St cells, as measured by membrane microviscosity, using the Shinitzki procedure. Isolation and gross chemical analysis of the TA3-Ha ascites fluid component was carried out. Results, so far, indicate that the active site of this product is probably carbohydrate in nature. The possible mode of action of such component in tumor growth enhancement is most probably by overwhelming and neutralizing immunocytes capable of recognition and eventually cytotoxic action.", "contents": "Discussion paper: dual effects of tumor antigens: induction of tumor resistance or tumor growth enhancement. TA3-HA nonspecific tumors growing in ascites form shed their membrane components into the ascites fluid. This product can induce tumor growth enhancement if given together with or after i.p. tumor inoculation in relatively large quantities, but if given i.m. in small quantities, several days before tumor challenge, the mice show an elevated resistance to the tumor. The strictly strain-specific TA3-St line does not release such membrane components into the ascites fluid. It has also been found that the TA3-HA cells have a larger membrane fluidity than the TA3-St cells, as measured by membrane microviscosity, using the Shinitzki procedure. Isolation and gross chemical analysis of the TA3-Ha ascites fluid component was carried out. Results, so far, indicate that the active site of this product is probably carbohydrate in nature. The possible mode of action of such component in tumor growth enhancement is most probably by overwhelming and neutralizing immunocytes capable of recognition and eventually cytotoxic action."}
{"id": "PMID:194515", "title": "Discussion paper: loss of cellular antigens during malignant transformation.", "content": "Normal human diploid cells, such as WE-38, transformed by an oncogenic virus, SV40, are greatly depleted of a cathodal esterase isozyme using both immunological and enzymatic criteria. This cathodal esterase is primate-specific and associated with lysosomes of many different tissue cells. It provides a clear example of antigenic loss associated with malignant change.", "contents": "Discussion paper: loss of cellular antigens during malignant transformation. Normal human diploid cells, such as WE-38, transformed by an oncogenic virus, SV40, are greatly depleted of a cathodal esterase isozyme using both immunological and enzymatic criteria. This cathodal esterase is primate-specific and associated with lysosomes of many different tissue cells. It provides a clear example of antigenic loss associated with malignant change."}
{"id": "PMID:194516", "title": "Discussion paper: specific paralysis of the antitumor cellular immune response produced by growing tumors studied with a radioisotope footpad assay.", "content": "The kinetics of the antitumor cellular immune response of mice with progressively growing syngeneic tumors were determined in vivo using a quantitative radioisotopic footpad assay. A close correlation was found between the size of the tumor and the degree of the cellular immune response. An initial phase of cellular immune stimulation was followed by specific suppression and subsequent immunologic paralysis as the tumor grew larger. This immune paralysis was attributed to increased tumor load since a homogenate of an SV40 transformed fibrosarcoma injected intraperitoneally into tumor-immune mice specifically depressed their cellular immune response. The fraction of the tumor homogenate that brought about this depression was present in the high speed supernatant and pellet of a 3M KCl extract of the tumor. The specificity of the depression was determined in vivo by the radioisotopic footpad assay and in vitro by a 51Cr cytolysis assay. Unwashed spleen cells harvested from mice bearing large tumors were unreactive in a local adoptive footpad assay. However, reactivity could be restored by repeatedly washing the spleen cells.", "contents": "Discussion paper: specific paralysis of the antitumor cellular immune response produced by growing tumors studied with a radioisotope footpad assay. The kinetics of the antitumor cellular immune response of mice with progressively growing syngeneic tumors were determined in vivo using a quantitative radioisotopic footpad assay. A close correlation was found between the size of the tumor and the degree of the cellular immune response. An initial phase of cellular immune stimulation was followed by specific suppression and subsequent immunologic paralysis as the tumor grew larger. This immune paralysis was attributed to increased tumor load since a homogenate of an SV40 transformed fibrosarcoma injected intraperitoneally into tumor-immune mice specifically depressed their cellular immune response. The fraction of the tumor homogenate that brought about this depression was present in the high speed supernatant and pellet of a 3M KCl extract of the tumor. The specificity of the depression was determined in vivo by the radioisotopic footpad assay and in vitro by a 51Cr cytolysis assay. Unwashed spleen cells harvested from mice bearing large tumors were unreactive in a local adoptive footpad assay. However, reactivity could be restored by repeatedly washing the spleen cells."}
{"id": "PMID:194518", "title": "Inhibition of tumor and fetal tissue growth in newborn recipients.", "content": "A comparative study of growth of a variety of fetal tissues and transplantable tumors in syngeneic newborn and adult mice was carried out. Tumors used in the experiments arose spontaneously (hepatomas, mammary gland adenocarcinoma) or resulted from malignant conversion of ectopic transplants either of fetal tissues (urinary bladder carcinoma, adenocarcinoma of small intestine, stomach sarcoma) or of adult animal tissues (ovary carcinoma) in syngeneic system. The growth of \"teratomas\" developed after transplantation of minced tissues of 18-20-day fetuses was considerably inferior in newborn syngeneic recipients as compared to analogous transplants in adults. Inhibition of tumor growth was also observed in newborn animals. It was manifested in prolongation of latent period before tumor node appearance as well as in slowing down of growth rate of developed tumors. Only one tumor, mammary gland adenocarcinoma, proved to be an exception, its growth being equally progressive in newborn and adult recipients. At transplantation of tumor cells mixed with lymphocytes of adult mouse spleen, stimulation of tumor growth in newborns and inhibition of growth in adult recipients was observed. It is suggested that there exists a special type of cellular or humoral mechanism controlling tumor growth in newborns. The activity of such factors is conceivably based on fetal antigens as targets.", "contents": "Inhibition of tumor and fetal tissue growth in newborn recipients. A comparative study of growth of a variety of fetal tissues and transplantable tumors in syngeneic newborn and adult mice was carried out. Tumors used in the experiments arose spontaneously (hepatomas, mammary gland adenocarcinoma) or resulted from malignant conversion of ectopic transplants either of fetal tissues (urinary bladder carcinoma, adenocarcinoma of small intestine, stomach sarcoma) or of adult animal tissues (ovary carcinoma) in syngeneic system. The growth of \"teratomas\" developed after transplantation of minced tissues of 18-20-day fetuses was considerably inferior in newborn syngeneic recipients as compared to analogous transplants in adults. Inhibition of tumor growth was also observed in newborn animals. It was manifested in prolongation of latent period before tumor node appearance as well as in slowing down of growth rate of developed tumors. Only one tumor, mammary gland adenocarcinoma, proved to be an exception, its growth being equally progressive in newborn and adult recipients. At transplantation of tumor cells mixed with lymphocytes of adult mouse spleen, stimulation of tumor growth in newborns and inhibition of growth in adult recipients was observed. It is suggested that there exists a special type of cellular or humoral mechanism controlling tumor growth in newborns. The activity of such factors is conceivably based on fetal antigens as targets."}
{"id": "PMID:194521", "title": "Optochiasmatic syndrome from adhesive arachnoiditis with coexisting hypophyseal adenoma: case report.", "content": "Adhesive arachnoiditis is an occasional finding during neurosurgical operations for pituitary adenoma, previously treated by radiation therapy. A case where an arachnoidal process was found in combination with an eosinophilic pituitary adenoma, which had never been treated by irradiation, is reported. A 44-year-old woman at the time of surgery with scarce endocrinologic symptoms had suffered visual loss from 2 episodes, 18 years apart. Analysis of her symptoms, neuro-ophthalmologic findings and neurodadiologic features suggest that her visual damage was due to an optochiasmatic arachnoiditis, rather than to the tumor itself.", "contents": "Optochiasmatic syndrome from adhesive arachnoiditis with coexisting hypophyseal adenoma: case report. Adhesive arachnoiditis is an occasional finding during neurosurgical operations for pituitary adenoma, previously treated by radiation therapy. A case where an arachnoidal process was found in combination with an eosinophilic pituitary adenoma, which had never been treated by irradiation, is reported. A 44-year-old woman at the time of surgery with scarce endocrinologic symptoms had suffered visual loss from 2 episodes, 18 years apart. Analysis of her symptoms, neuro-ophthalmologic findings and neurodadiologic features suggest that her visual damage was due to an optochiasmatic arachnoiditis, rather than to the tumor itself."}
{"id": "PMID:194525", "title": "[Histochemical and ultrastructural study of cytochrome-oxydase in basal cell epithelioma].", "content": "The activity of cytochrome-oxydase is less pronounced in the basal cell epithelioma than in the basal cells of the surrounding normal epidermis. The electron microscopic study of the localisation of the enzyme reveals that the cells of the basal cell epithelioma contain two types of mitochondria, the first of which having the same size as the epidermal mitochondria, and the other being giant mitochondria. The latter seem to be less active. The weak reactivity of the basal cell epithelioma for cytochrome-oxydase is probably due to the reduction of the cristae in mitochondria and to the functional deficiency of the giant mitochondria.", "contents": "[Histochemical and ultrastructural study of cytochrome-oxydase in basal cell epithelioma]. The activity of cytochrome-oxydase is less pronounced in the basal cell epithelioma than in the basal cells of the surrounding normal epidermis. The electron microscopic study of the localisation of the enzyme reveals that the cells of the basal cell epithelioma contain two types of mitochondria, the first of which having the same size as the epidermal mitochondria, and the other being giant mitochondria. The latter seem to be less active. The weak reactivity of the basal cell epithelioma for cytochrome-oxydase is probably due to the reduction of the cristae in mitochondria and to the functional deficiency of the giant mitochondria."}
{"id": "PMID:194526", "title": "Prognosis of carcinoma of the breast in women under 25 years of age.", "content": "In 1960 to 1969 twenty six women below 25 years were operated on because of mammary carcinoma. All eighteen patients in stage 0 and I had a five-year cure. The corresponding rate for seven women in stage II was 43%. Of eight women with a poorly differentiated or anaplastic growth, 38% survived for more than five years. The corresponding figure for those with a well differentiated tumour was 100%. The prognosis in young women is thus good provided the malignant breast tumour is diagnosed and treated in good time, and it is better than that in elderly women.", "contents": "Prognosis of carcinoma of the breast in women under 25 years of age. In 1960 to 1969 twenty six women below 25 years were operated on because of mammary carcinoma. All eighteen patients in stage 0 and I had a five-year cure. The corresponding rate for seven women in stage II was 43%. Of eight women with a poorly differentiated or anaplastic growth, 38% survived for more than five years. The corresponding figure for those with a well differentiated tumour was 100%. The prognosis in young women is thus good provided the malignant breast tumour is diagnosed and treated in good time, and it is better than that in elderly women."}
{"id": "PMID:194522", "title": "Adenoidcystic carcinoma (cylindroma) of the parotid gland.", "content": "Adenoidcystic carcinoma or cylindroma of the parotid gland is a slow-growing, relentless, and often lethal disease which kills usually by local occurrence and direct extension of the disease. The reported incidence of adenoidcystic carcinoma with reference to other parotid malignancies varies from 5% to 37%. The incidence in this series is 36%. The presence of facial nerve involvement adversely affects the long-term survival. Some authors regard facial nerve involvement as an indication of noncurability. The incidence of local pain is reported to be as high as 50% and is thought to be caused by perineural invasion by the tumor. This is well-documented histopathologically. There is no uniform or standard treatment for this disorder. Extensive resection of the parotid gland (including the facial nerve if there is any indication of involvement), followed by external irradiation to the parotid area and upper neck is the most rational approach to the problem. This is supported both in the review of the literature and from the present series. A radical neck dissection is not included as part of initial therapy unless there are clinically suspicious cervical nodes. Postoperative radiotherapy appears indicated in all cases of adenoidcystic carcinoma of the parotid gland. Four case histories are presented which demonstrate the hallmark characteristics of the disease, i.e. multiple cranial nerve deficits, facial pain and subsequent death by direct intracranial extension of disease. The protracted, relentless course of the disease is well-documented in one case in which 25 local recurrences developed over an 18-year period.", "contents": "Adenoidcystic carcinoma (cylindroma) of the parotid gland. Adenoidcystic carcinoma or cylindroma of the parotid gland is a slow-growing, relentless, and often lethal disease which kills usually by local occurrence and direct extension of the disease. The reported incidence of adenoidcystic carcinoma with reference to other parotid malignancies varies from 5% to 37%. The incidence in this series is 36%. The presence of facial nerve involvement adversely affects the long-term survival. Some authors regard facial nerve involvement as an indication of noncurability. The incidence of local pain is reported to be as high as 50% and is thought to be caused by perineural invasion by the tumor. This is well-documented histopathologically. There is no uniform or standard treatment for this disorder. Extensive resection of the parotid gland (including the facial nerve if there is any indication of involvement), followed by external irradiation to the parotid area and upper neck is the most rational approach to the problem. This is supported both in the review of the literature and from the present series. A radical neck dissection is not included as part of initial therapy unless there are clinically suspicious cervical nodes. Postoperative radiotherapy appears indicated in all cases of adenoidcystic carcinoma of the parotid gland. Four case histories are presented which demonstrate the hallmark characteristics of the disease, i.e. multiple cranial nerve deficits, facial pain and subsequent death by direct intracranial extension of disease. The protracted, relentless course of the disease is well-documented in one case in which 25 local recurrences developed over an 18-year period."}
{"id": "PMID:194527", "title": "A quantitative study of the ABH red cell antigens in the Kulamwo of Ivory Coast.", "content": "The agglutination percentages given by various erythrocytes with reference sera have been compared in blood samples from Kulamwos living in the Ivory Coast and of blood donors of the regional transfusion centre of Toulouse. The study of O, A, B and AB phenotypes shows: 1. in O Kulamwos a higher agglutination percentage with anti-H than in Toulousains; 2. in B Kulamwos a higher agglutination percentage with anti-B than in Toulousains; 3. in A Kulamwos a very marked frequency of A intermediate which can be classified in different categories due to the variability of their agglutination percentage with anti-A1 and anti-H sera.", "contents": "A quantitative study of the ABH red cell antigens in the Kulamwo of Ivory Coast. The agglutination percentages given by various erythrocytes with reference sera have been compared in blood samples from Kulamwos living in the Ivory Coast and of blood donors of the regional transfusion centre of Toulouse. The study of O, A, B and AB phenotypes shows: 1. in O Kulamwos a higher agglutination percentage with anti-H than in Toulousains; 2. in B Kulamwos a higher agglutination percentage with anti-B than in Toulousains; 3. in A Kulamwos a very marked frequency of A intermediate which can be classified in different categories due to the variability of their agglutination percentage with anti-A1 and anti-H sera."}
{"id": "PMID:194528", "title": "Experience with a new agar culture medium for demonstrating the presence of anaerobic bacteria.", "content": "In view of the fact that anaerobic diagnostics have become a matter of primary importance, the authors have developed the RCM medium with certain modifications. Owing to its good keeping quality, this medium can be used also on smaller laboratories for demonstrating the presence of anaerobic bacteria and for carrying out germ counts. It constitutes and adequate base for the anaerobic blood medium and for the Wilson-Blair medium, and also for the determination of the antibiotic resistance of the anaerobic bacteria. The sensitivity of this medium surpasses that of the thioglycollate medium, and is suitable in its carbohydrate-free form also for testing the strains for their sugar-fermentative capactiy. Our work was aimed at serving the anaerobic diagnostics of clinical laboratories, and at serving at the same time the method of demonstrating the presence of anaerobes becoming increasingle important in the food industry.", "contents": "Experience with a new agar culture medium for demonstrating the presence of anaerobic bacteria. In view of the fact that anaerobic diagnostics have become a matter of primary importance, the authors have developed the RCM medium with certain modifications. Owing to its good keeping quality, this medium can be used also on smaller laboratories for demonstrating the presence of anaerobic bacteria and for carrying out germ counts. It constitutes and adequate base for the anaerobic blood medium and for the Wilson-Blair medium, and also for the determination of the antibiotic resistance of the anaerobic bacteria. The sensitivity of this medium surpasses that of the thioglycollate medium, and is suitable in its carbohydrate-free form also for testing the strains for their sugar-fermentative capactiy. Our work was aimed at serving the anaerobic diagnostics of clinical laboratories, and at serving at the same time the method of demonstrating the presence of anaerobes becoming increasingle important in the food industry."}
{"id": "PMID:194524", "title": "Diffuse otitis externa: clinical and microbiologic findings in the course of a multicenter study on a new otic solution.", "content": "This report reviews the literature on the epidemiology, pathogenesis and bacteriology of diffuse otitis externa. Four departments of otolaryngology undertook identical studies of these factors, as well as the efficacy and safety of two similar antibiotic-corticosteroid formulations; one a suspension and the other a clear solution. A total of 239 patients, or 283 ears, were studied, utilizing objective clinical as well as correlative bacteriologic criteria. A high degree of clinical and bacteriologic efficacy was demonstrated by the medications irrespective of the formulation, infecting organism, patient's age, length of disease history, severity, or geographic location. There was no statistical difference between either formulation, both achieving a clinical efficacy rate of 97% and a bacteriologic efficacy rate of 83%. Drug related side effects occurred in 1.9% of the patients given the solution and in 1.1% of those given the suspension.", "contents": "Diffuse otitis externa: clinical and microbiologic findings in the course of a multicenter study on a new otic solution. This report reviews the literature on the epidemiology, pathogenesis and bacteriology of diffuse otitis externa. Four departments of otolaryngology undertook identical studies of these factors, as well as the efficacy and safety of two similar antibiotic-corticosteroid formulations; one a suspension and the other a clear solution. A total of 239 patients, or 283 ears, were studied, utilizing objective clinical as well as correlative bacteriologic criteria. A high degree of clinical and bacteriologic efficacy was demonstrated by the medications irrespective of the formulation, infecting organism, patient's age, length of disease history, severity, or geographic location. There was no statistical difference between either formulation, both achieving a clinical efficacy rate of 97% and a bacteriologic efficacy rate of 83%. Drug related side effects occurred in 1.9% of the patients given the solution and in 1.1% of those given the suspension."}
{"id": "PMID:194534", "title": "Mannitol oxidation in two Micromonospora isolates and in representative species of other actinomycetes.", "content": "Mannitol kinase and mannitol-1-phosphate dehydrogenase activities were detected in two Micromonospora isolates. The presence of these enzyme activities indicates that mannitol is catabolized first to mannitol-1-phosphate and then to fructose-6-phosphate. Mannitol-oxidizing enzymes were also surveyed in representative species of four other genera of actinomycetes. Mannitol-1-phosphate dehydrogenase was detected in cell-free extracts of Streptomyces lactamdurans. In contrast, cell-free extracts of Mycobacterium smegmatis, Nocardia erythrophila, Streptomyces lavendulae, and Actinoplanes missouriensis contained mannitol dehydrogenase activity but no detectable mannitol-1-phosphate dehydrogenase activity. The mannitol dehydrogenase activities in the latter species support the operation of a pathway for catabolism of mannitol that involves the oxidation of mannitol to fructose, followed by phosphorylation to fructose-6-phosphate.", "contents": "Mannitol oxidation in two Micromonospora isolates and in representative species of other actinomycetes. Mannitol kinase and mannitol-1-phosphate dehydrogenase activities were detected in two Micromonospora isolates. The presence of these enzyme activities indicates that mannitol is catabolized first to mannitol-1-phosphate and then to fructose-6-phosphate. Mannitol-oxidizing enzymes were also surveyed in representative species of four other genera of actinomycetes. Mannitol-1-phosphate dehydrogenase was detected in cell-free extracts of Streptomyces lactamdurans. In contrast, cell-free extracts of Mycobacterium smegmatis, Nocardia erythrophila, Streptomyces lavendulae, and Actinoplanes missouriensis contained mannitol dehydrogenase activity but no detectable mannitol-1-phosphate dehydrogenase activity. The mannitol dehydrogenase activities in the latter species support the operation of a pathway for catabolism of mannitol that involves the oxidation of mannitol to fructose, followed by phosphorylation to fructose-6-phosphate."}
{"id": "PMID:194535", "title": "Comparison of sulfite-polymyxin-sulfadiazine medium and tryptose-sulfite-cycloserine medium without egg yolk for recovering Clostridium perfringens.", "content": "The overall recoveries of spores and of actively growing, heat-stressed, coldshocked, and frozen cells of five strains of Clostridium perfringens were significantly greater (95% confidence limits) on tryptose-sulfite-cycloserine medium without egg yolk than on sulfite-polymyxin-sulfadiazine medium.", "contents": "Comparison of sulfite-polymyxin-sulfadiazine medium and tryptose-sulfite-cycloserine medium without egg yolk for recovering Clostridium perfringens. The overall recoveries of spores and of actively growing, heat-stressed, coldshocked, and frozen cells of five strains of Clostridium perfringens were significantly greater (95% confidence limits) on tryptose-sulfite-cycloserine medium without egg yolk than on sulfite-polymyxin-sulfadiazine medium."}
{"id": "PMID:194536", "title": "Glucagonoma syndrome. Report of two cases and literature review.", "content": "The glucagonoma syndrome is characterized by dermatitis, stomatitis, elevated serum glucagon levels, abnormal glucose tolerance, weight loss, and anemia--all in association with a glucagon-secreting alpha-cell tumor of the pancreas. A review of 21 cases showed strikingly similar features. A generalized, symmetrical dermatitis initially appeared to be asteatotic or eczematous over the perineum, buttocks, and lower extremities. Gradually, a more characteristic migratory necrolytic erythema with transient bulla formation and erosions developed in intertriginous and dependent areas. Histologically, the most specific features included necrolysis of the upper epidermis, with liquefaction necrosis of the granular cell layer and subcorneal clefting or blister formation. The dermatologist is often first to examine such patients; early recognition of this syndrome with prompt surgical removal of the primary pancreatic lesion may afford cure of the neoplasm.", "contents": "Glucagonoma syndrome. Report of two cases and literature review. The glucagonoma syndrome is characterized by dermatitis, stomatitis, elevated serum glucagon levels, abnormal glucose tolerance, weight loss, and anemia--all in association with a glucagon-secreting alpha-cell tumor of the pancreas. A review of 21 cases showed strikingly similar features. A generalized, symmetrical dermatitis initially appeared to be asteatotic or eczematous over the perineum, buttocks, and lower extremities. Gradually, a more characteristic migratory necrolytic erythema with transient bulla formation and erosions developed in intertriginous and dependent areas. Histologically, the most specific features included necrolysis of the upper epidermis, with liquefaction necrosis of the granular cell layer and subcorneal clefting or blister formation. The dermatologist is often first to examine such patients; early recognition of this syndrome with prompt surgical removal of the primary pancreatic lesion may afford cure of the neoplasm."}
{"id": "PMID:194537", "title": "Necrolytic migratory erythema. Distinctive dermatosis of the glucagonoma syndrome.", "content": "Glucagon-secreting tumors of the pancreatic islets (glucagonomas) produce a distinctive syndrome in which weight loss, diabetes mellitus, anemia,and prominent mucocutaneous findings occur. The cutaneous component-necrolytic migratory erythema--may be polymorphous, but most commonly manifests as erosions and crusts of the groin, perineum, buttocks, distal part of the extremities, and central area of the face. Alternatively, scaly papules and plaques may predominate in these areas. The eruption may resemble such dermatoses as pemphigus foliaceus, acrodermatitis enteropathica, chronic mucocutaneous candidiasis, psoriasis, and severe seborrheic dermatitis. Two patients with chronic, previously undiagnosed dermatoses had necrolytic migratory erythemia, which led to the discovery of glucagonomas present in each. In one patient surgical resection of the tumor resulted in total clearing of the rash within 48 hours. Awareness of this distinctive entity may lead to early diagnosis and, possibly, cure.", "contents": "Necrolytic migratory erythema. Distinctive dermatosis of the glucagonoma syndrome. Glucagon-secreting tumors of the pancreatic islets (glucagonomas) produce a distinctive syndrome in which weight loss, diabetes mellitus, anemia,and prominent mucocutaneous findings occur. The cutaneous component-necrolytic migratory erythema--may be polymorphous, but most commonly manifests as erosions and crusts of the groin, perineum, buttocks, distal part of the extremities, and central area of the face. Alternatively, scaly papules and plaques may predominate in these areas. The eruption may resemble such dermatoses as pemphigus foliaceus, acrodermatitis enteropathica, chronic mucocutaneous candidiasis, psoriasis, and severe seborrheic dermatitis. Two patients with chronic, previously undiagnosed dermatoses had necrolytic migratory erythemia, which led to the discovery of glucagonomas present in each. In one patient surgical resection of the tumor resulted in total clearing of the rash within 48 hours. Awareness of this distinctive entity may lead to early diagnosis and, possibly, cure."}
{"id": "PMID:194538", "title": "Generalized acute mucocutaneous herpes simplex type 2 with fatal outcome.", "content": "To our knowledge, we present the first culturally documented case of generalized acute mucocutaneous herpes simplex type 2 in an immunosuppressed adult who died during the course of the disease. The picture of the clinical spectrum of herpetic disease in immunosuppressed patients is detailed, and the need for typing the virus, particularly in the disseminated form, and for clarifying possible differences in epidemiology, clinical expression, and prognosis is emphasized.", "contents": "Generalized acute mucocutaneous herpes simplex type 2 with fatal outcome. To our knowledge, we present the first culturally documented case of generalized acute mucocutaneous herpes simplex type 2 in an immunosuppressed adult who died during the course of the disease. The picture of the clinical spectrum of herpetic disease in immunosuppressed patients is detailed, and the need for typing the virus, particularly in the disseminated form, and for clarifying possible differences in epidemiology, clinical expression, and prognosis is emphasized."}
{"id": "PMID:194539", "title": "Perinatal cytomegalovirus infection in man.", "content": "In a prospective study of 148 children from urbanized southern Finland 3 were found to be congenitally and 48 perinatally infected with cytomegalovirus (CMV), while 6 developed \"late\" infection during the first year of life. During pregnancy and the first year after delivery 23 of the mothers had no CMV antibodies; none of the children of these seronegative mothers developed any type of CMV infection. Fresh blood exchange transfusions did not increase the risk of CMV infection. The data support the hypothesis that the mother is the source of perinatal CMV infection. Children with a low birthweight not due to prematurity, and first children seem to run a greater risk of acquiring perinatal CMV infection. If the child is breast fed up to the age of 2 months the risk seems to be increased. Perinatal CMV infection gave rise to no symptoms or signs and had no effect on growth or on motor and psychosocial development during the first year of life.", "contents": "Perinatal cytomegalovirus infection in man. In a prospective study of 148 children from urbanized southern Finland 3 were found to be congenitally and 48 perinatally infected with cytomegalovirus (CMV), while 6 developed \"late\" infection during the first year of life. During pregnancy and the first year after delivery 23 of the mothers had no CMV antibodies; none of the children of these seronegative mothers developed any type of CMV infection. Fresh blood exchange transfusions did not increase the risk of CMV infection. The data support the hypothesis that the mother is the source of perinatal CMV infection. Children with a low birthweight not due to prematurity, and first children seem to run a greater risk of acquiring perinatal CMV infection. If the child is breast fed up to the age of 2 months the risk seems to be increased. Perinatal CMV infection gave rise to no symptoms or signs and had no effect on growth or on motor and psychosocial development during the first year of life."}
{"id": "PMID:194540", "title": "Lack of effect of phototherapy on plasma cyclic-AMP in newborn infants.", "content": "The effect of phototherapy on plasma cyclic-AMP in newborn infants has been studied. Our results suggest that phototherapy does not produce appreciable changes in plasma cyclic-AMP levels.", "contents": "Lack of effect of phototherapy on plasma cyclic-AMP in newborn infants. The effect of phototherapy on plasma cyclic-AMP in newborn infants has been studied. Our results suggest that phototherapy does not produce appreciable changes in plasma cyclic-AMP levels."}
{"id": "PMID:194541", "title": "Thoracic neurolophomas.", "content": "Neural crest cells are unique. Few tissues found in the embryo are expressed with such diversity in adults. Cellular differentiation occurs simultaneously with widespread migration. Neural crest cell neoplasia results in some of the most common tumors clinically encountered. As a group, these tumors are called neurolophomas. This report describes the neural crest formation, the tissues normally derived from it, a classification of the neural crest tumors, and a review of such tumors as they arise in the thorax.", "contents": "Thoracic neurolophomas. Neural crest cells are unique. Few tissues found in the embryo are expressed with such diversity in adults. Cellular differentiation occurs simultaneously with widespread migration. Neural crest cell neoplasia results in some of the most common tumors clinically encountered. As a group, these tumors are called neurolophomas. This report describes the neural crest formation, the tissues normally derived from it, a classification of the neural crest tumors, and a review of such tumors as they arise in the thorax."}
{"id": "PMID:194542", "title": "The effect of enkephalin and enkephalin analogs on the guinea-pig ileum and rat brain opilate receptor.", "content": "We have synthesized the two naturally occurring enkephalins (Methionine-Enkephalin and Leucine-Enkephalin) as well as four other analogs (Methinonine-Enkephalin amide, S-Benzyl sulphonium analog of Methionine-Enkephalin, 3-Benzyl-tyrosine analog of Methionine-Enkephalin and 3-Benzyl-tyrosine analog of Leucine-Enkephalin) in order to study their relative potency and their inactivation of different tissues. Morphine-like activity of the peptides was determined by measuring their inhibitory effect in the guinea-pig ileum and their interaction with the brain opiate receptor; the order of affinity of the three most active peptides (Methionine-Enkephalin amide greater than Methionine-Enkephalin greater than Leucine-Enkephalin) for the rat brain opiate receptor was found to be the same in the guinea-pig ileum. The rate of inactivation of the peptides was also studied in the guinea-pig ileum and in the rat brain membrane preparation. Methionine-Enkephalin amide was relatively more resistant to the ileum peptidases than the other peptides, but was destroyed at the same rate by brain membranes; this variation in inactivation of Methionine-Enkephalin amide probably indicates the presence of differnet peptidases in each tissue preparation.", "contents": "The effect of enkephalin and enkephalin analogs on the guinea-pig ileum and rat brain opilate receptor. We have synthesized the two naturally occurring enkephalins (Methionine-Enkephalin and Leucine-Enkephalin) as well as four other analogs (Methinonine-Enkephalin amide, S-Benzyl sulphonium analog of Methionine-Enkephalin, 3-Benzyl-tyrosine analog of Methionine-Enkephalin and 3-Benzyl-tyrosine analog of Leucine-Enkephalin) in order to study their relative potency and their inactivation of different tissues. Morphine-like activity of the peptides was determined by measuring their inhibitory effect in the guinea-pig ileum and their interaction with the brain opiate receptor; the order of affinity of the three most active peptides (Methionine-Enkephalin amide greater than Methionine-Enkephalin greater than Leucine-Enkephalin) for the rat brain opiate receptor was found to be the same in the guinea-pig ileum. The rate of inactivation of the peptides was also studied in the guinea-pig ileum and in the rat brain membrane preparation. Methionine-Enkephalin amide was relatively more resistant to the ileum peptidases than the other peptides, but was destroyed at the same rate by brain membranes; this variation in inactivation of Methionine-Enkephalin amide probably indicates the presence of differnet peptidases in each tissue preparation."}
{"id": "PMID:194543", "title": "Salt-wasting bronchorrhea and its mechanisms.", "content": "A 56-year old woman, with the diffuse form of bronchioloalveolar cell carcinoma, developed massive bronchorrhea, resulting in severe fluid and electrolyte depletion when her oral intake was compromised. Chemical analysis of the bronchial secretions and the ultrastructural features of the tumor cells support the concept of an active secretory process. The lactic dehydrogenase (LDH) isoenzyme pattern of the fluid is similar to that found in fetal cells. The neoplastic cells may acquire a more primitive LDH pattern.", "contents": "Salt-wasting bronchorrhea and its mechanisms. A 56-year old woman, with the diffuse form of bronchioloalveolar cell carcinoma, developed massive bronchorrhea, resulting in severe fluid and electrolyte depletion when her oral intake was compromised. Chemical analysis of the bronchial secretions and the ultrastructural features of the tumor cells support the concept of an active secretory process. The lactic dehydrogenase (LDH) isoenzyme pattern of the fluid is similar to that found in fetal cells. The neoplastic cells may acquire a more primitive LDH pattern."}
{"id": "PMID:194544", "title": "[Albright's type II osteodystrophy and hypothyroidism due to TSH deficiency. Apropos of a case in a child].", "content": "The report is dealing with a 10 year-old girl. The diagnosis of Albright's type II osteodystrophy relied on clinical, radiological and biological symptoms: evocative dysmorphic syndrome and absence of disturbances in the phosphocalcic metabolism. Hypothyroidism was secondary to an isolated defect in TSH, and a TRH stimulation test did not induce an increase in plasma TSH.", "contents": "[Albright's type II osteodystrophy and hypothyroidism due to TSH deficiency. Apropos of a case in a child]. The report is dealing with a 10 year-old girl. The diagnosis of Albright's type II osteodystrophy relied on clinical, radiological and biological symptoms: evocative dysmorphic syndrome and absence of disturbances in the phosphocalcic metabolism. Hypothyroidism was secondary to an isolated defect in TSH, and a TRH stimulation test did not induce an increase in plasma TSH."}
{"id": "PMID:194545", "title": "[A symptomatic parathyroid adenoma. Value of parathyroid hormone determination through selective catheterization of the thyroid veins].", "content": "A parathyroid adenoma is reported in a girl aged 12 years in whom hypercalcaemia was discovered by chance. Investigation of calcium metabolism suggested the diagnosis of hyperparathyroidism and studies of the urinary cyclic AMP and determination of the plasma parathyroid hormone concentration further added to the evidence. The diagnosis of parathyroid adenoma was made after determination of the parathyroid hormone concentration at various sights during selective catheterization of the tyroid veins. This was confirmed at surgery. In this patient the place of catheterization of the inferior thyroid veins in the early diagnosis of primary hyperparathyroidism is discussed.", "contents": "[A symptomatic parathyroid adenoma. Value of parathyroid hormone determination through selective catheterization of the thyroid veins]. A parathyroid adenoma is reported in a girl aged 12 years in whom hypercalcaemia was discovered by chance. Investigation of calcium metabolism suggested the diagnosis of hyperparathyroidism and studies of the urinary cyclic AMP and determination of the plasma parathyroid hormone concentration further added to the evidence. The diagnosis of parathyroid adenoma was made after determination of the parathyroid hormone concentration at various sights during selective catheterization of the tyroid veins. This was confirmed at surgery. In this patient the place of catheterization of the inferior thyroid veins in the early diagnosis of primary hyperparathyroidism is discussed."}
{"id": "PMID:194546", "title": "[Islet cell adenoma with neonatal onset. Clinical, hormonological and ultrastructural study of a case].", "content": "A case of hyperinsulinism occuring in a newborn, with a birthweight of 4,050 g, is reported. The hypoglycaemia was refractory to the usual therapy (increase of glucose administration per os, and I.V., corticosteroids, glucagon, diazoxide). At surgery, undertaken at 9 days of age, an adenomatous nodule was removed along with the left part of the pancreas. Death occurred at 18 days, after the child had developed a transitory acidoketosic diabetes and an encephalopathy. Measurement of insulin by radio-immunoassay revealed a strong increase in the ratio insulin/glycaemia, characteristic of nesidioblastoma, as well as a high concentration of insulin in the tumor as compared to normal tissue. On the ultrastructural level, the observed features differed from those seen in children and adults and showed an abnormal overload of dense deposits in the cytoplasm of some histiocytes.", "contents": "[Islet cell adenoma with neonatal onset. Clinical, hormonological and ultrastructural study of a case]. A case of hyperinsulinism occuring in a newborn, with a birthweight of 4,050 g, is reported. The hypoglycaemia was refractory to the usual therapy (increase of glucose administration per os, and I.V., corticosteroids, glucagon, diazoxide). At surgery, undertaken at 9 days of age, an adenomatous nodule was removed along with the left part of the pancreas. Death occurred at 18 days, after the child had developed a transitory acidoketosic diabetes and an encephalopathy. Measurement of insulin by radio-immunoassay revealed a strong increase in the ratio insulin/glycaemia, characteristic of nesidioblastoma, as well as a high concentration of insulin in the tumor as compared to normal tissue. On the ultrastructural level, the observed features differed from those seen in children and adults and showed an abnormal overload of dense deposits in the cytoplasm of some histiocytes."}
{"id": "PMID:194547", "title": "Family intervention with severely disturbed inpatients.", "content": "Although there is considerable evidence that family variables and interaction patterns affect the duration of hospitalization and frequency of readmission of psychiatric patients, it is rare to find inpatient facilities having psychotherapeutic programs that systematically stress family interventions. This article discusses the difficulties encountered by both families and staff as they cope with the issues of hospitalization, suggests a structured, patient-oriented family approach, and recommends some specific techniques for short-term work with families of severely disturbed inpatients.", "contents": "Family intervention with severely disturbed inpatients. Although there is considerable evidence that family variables and interaction patterns affect the duration of hospitalization and frequency of readmission of psychiatric patients, it is rare to find inpatient facilities having psychotherapeutic programs that systematically stress family interventions. This article discusses the difficulties encountered by both families and staff as they cope with the issues of hospitalization, suggests a structured, patient-oriented family approach, and recommends some specific techniques for short-term work with families of severely disturbed inpatients."}
{"id": "PMID:194548", "title": "Invasion of malignant cells into cultured embryonic substrates.", "content": "To study malignant invasion, we associated tissue and cell culture fragments, with adhesive and non-adhesive living substrates in vitro (11). Non malignant mesonephros, quail heart and BHK-cells, as well as malignant HeLa-, Hepatoma-, Harding-Passey melanoma-, Py-, TLX5 lymphoma- and Schmidt-Ruppin sarcoma cells, were transplanted into cultured organ fragments of chick embryos and chick blastoderms. Malignant invasion was evaluated on the basis of the following histological criteria: 1. changes in organization of the graft. 2. infiltration of cells from the graft into the substrate, 3. degenerative alterations of the substrate. It was shown that adhesion of the graft to the substrate is a prerequisite for malignant invasion. Invasion into non-adhesive substrates, such as the apical side of epithelia, was never observed. Contrary, all malignant cells did invade into adhesive substrates. Interposition of a vitelline membrane always inhibited the expression of invasiveness. The morphological pattern of invasion depended mainly on the architecture of the substrate and differential resistance of its various components explained well all histological pictures. From the latter observation and from the localization of degenerative changes in the substrate we inferred that malignant cells exert their deleterious effect most probably upon immediate contact with their host.", "contents": "Invasion of malignant cells into cultured embryonic substrates. To study malignant invasion, we associated tissue and cell culture fragments, with adhesive and non-adhesive living substrates in vitro (11). Non malignant mesonephros, quail heart and BHK-cells, as well as malignant HeLa-, Hepatoma-, Harding-Passey melanoma-, Py-, TLX5 lymphoma- and Schmidt-Ruppin sarcoma cells, were transplanted into cultured organ fragments of chick embryos and chick blastoderms. Malignant invasion was evaluated on the basis of the following histological criteria: 1. changes in organization of the graft. 2. infiltration of cells from the graft into the substrate, 3. degenerative alterations of the substrate. It was shown that adhesion of the graft to the substrate is a prerequisite for malignant invasion. Invasion into non-adhesive substrates, such as the apical side of epithelia, was never observed. Contrary, all malignant cells did invade into adhesive substrates. Interposition of a vitelline membrane always inhibited the expression of invasiveness. The morphological pattern of invasion depended mainly on the architecture of the substrate and differential resistance of its various components explained well all histological pictures. From the latter observation and from the localization of degenerative changes in the substrate we inferred that malignant cells exert their deleterious effect most probably upon immediate contact with their host."}
{"id": "PMID:194549", "title": "The role of cyclic adenosine 3',5'-monophosphate (cAMP) in the mechanism of action of tricyclic antiderpressants.", "content": "In the course of investigations on experimental arterial hypertension in rats, it has been stated, that imipramine prevents the development of hypertension and that is simultaneously causes an accumulation of cAMP in the vessel walls. The relationship between the two phenomena has been discussed.", "contents": "The role of cyclic adenosine 3',5'-monophosphate (cAMP) in the mechanism of action of tricyclic antiderpressants. In the course of investigations on experimental arterial hypertension in rats, it has been stated, that imipramine prevents the development of hypertension and that is simultaneously causes an accumulation of cAMP in the vessel walls. The relationship between the two phenomena has been discussed."}
{"id": "PMID:194550", "title": "Degeneration of aortic smooth muscle cells in swine fed excess vitamin D3.", "content": "Twenty-eight weanling swine were divided into two groups and fed a basal ration of corn and soybean meal or one containing a high fat and cholesterol supplement. One subgroup of each received 220,000 IU of vitamin D3 per kilogram. Grossly normal areas of the distal abdominal aorta were used for quantitative comparison of degenerated smooth muscle cells by electron microscopical cell counts. Degeneration was classified into rarefaction, condensation, and frequency per 100 nucleated cells. The frequency of dead cells was demonstrable between the swine fed excess vitamin D3 with or without high fat and cholesterol and those fed the basal ration alone, or frequencies of 7.9, 7.4, and 5.6 at 3 months of age (P less than .05) and 7.3, 6.2, and 5.1 at 6 months (P less than .05), respectively. No significant difference was demonstrable between the swine fed high fat and cholesterol without excess vitamin D3 and those fed the basal ration alone, or frequencies of 5.7 and 5.6 at 3 months of age and 5.5 and 5.1 at 6 months.", "contents": "Degeneration of aortic smooth muscle cells in swine fed excess vitamin D3. Twenty-eight weanling swine were divided into two groups and fed a basal ration of corn and soybean meal or one containing a high fat and cholesterol supplement. One subgroup of each received 220,000 IU of vitamin D3 per kilogram. Grossly normal areas of the distal abdominal aorta were used for quantitative comparison of degenerated smooth muscle cells by electron microscopical cell counts. Degeneration was classified into rarefaction, condensation, and frequency per 100 nucleated cells. The frequency of dead cells was demonstrable between the swine fed excess vitamin D3 with or without high fat and cholesterol and those fed the basal ration alone, or frequencies of 7.9, 7.4, and 5.6 at 3 months of age (P less than .05) and 7.3, 6.2, and 5.1 at 6 months (P less than .05), respectively. No significant difference was demonstrable between the swine fed high fat and cholesterol without excess vitamin D3 and those fed the basal ration alone, or frequencies of 5.7 and 5.6 at 3 months of age and 5.5 and 5.1 at 6 months."}
{"id": "PMID:194551", "title": "Interferon production and response to exogenous interferon in two cell lines of mouse brain origin persistently infected with Sendai virus.", "content": "Two persistently infected cell lines established from C3H mouse brain cells infected in vivo with Sendai virus were shown to differ with respect to interferon (IF) production and response to exogenous IF. MB/Sen carrier cells contained 1-5 per cent antigen positive cells when examined by immunofluorescence, and virus was occasionally recovered from the culture medium. MB/SenAS carrier cells were maintained with 0.16 per cent Sendai antiserum in the supernatant medium. All MB/SenAS cells contained viral antigen and infectious virus was present in the culture medium. MB/Sen released IF spontaneously into the culture medium. Further IF production could be stimulated in MB/Sen by superinfection with Newcastle disease virus (NDV) or vesicular stomatitis virus (VSV). Exogenous IF provided good protection against VSV challenge. In contrast, MB/SenAS produced no IF spontaneously but could be stimulated by NDV and VSV to produce IF. Exogenous IF failed to reduce the amount of VSV released into the supernatant fluid. Replication of VSV was restricted in MB/SenAS as shown by a 2.3 log10 lower virus yield compared to MB/Sen.", "contents": "Interferon production and response to exogenous interferon in two cell lines of mouse brain origin persistently infected with Sendai virus. Two persistently infected cell lines established from C3H mouse brain cells infected in vivo with Sendai virus were shown to differ with respect to interferon (IF) production and response to exogenous IF. MB/Sen carrier cells contained 1-5 per cent antigen positive cells when examined by immunofluorescence, and virus was occasionally recovered from the culture medium. MB/SenAS carrier cells were maintained with 0.16 per cent Sendai antiserum in the supernatant medium. All MB/SenAS cells contained viral antigen and infectious virus was present in the culture medium. MB/Sen released IF spontaneously into the culture medium. Further IF production could be stimulated in MB/Sen by superinfection with Newcastle disease virus (NDV) or vesicular stomatitis virus (VSV). Exogenous IF provided good protection against VSV challenge. In contrast, MB/SenAS produced no IF spontaneously but could be stimulated by NDV and VSV to produce IF. Exogenous IF failed to reduce the amount of VSV released into the supernatant fluid. Replication of VSV was restricted in MB/SenAS as shown by a 2.3 log10 lower virus yield compared to MB/Sen."}
{"id": "PMID:194552", "title": "Components of parainfluenza-3 virus, SLP-strain, reacting in assays of cell-mediated immunity in cattle.", "content": "Parainfluenza-3 virus was isolated by affinity chromatography, including a purification step with immobilized lectin Vicia erwilia. The peplomers of disintegrated virus were similarily isolated using another carbohydrate-specific lectin Vicia crotalaria. The whole virion and the peplomers were both active as antigens in the leucocyte migration inhibition, lymphocyte stimulation and skin hypersensitivity tests. The remaining virus material, freed of detergents used for virus disintegration and containing nucleocapsids, did not act as antigen in these tests of cell-mediated immunity.", "contents": "Components of parainfluenza-3 virus, SLP-strain, reacting in assays of cell-mediated immunity in cattle. Parainfluenza-3 virus was isolated by affinity chromatography, including a purification step with immobilized lectin Vicia erwilia. The peplomers of disintegrated virus were similarily isolated using another carbohydrate-specific lectin Vicia crotalaria. The whole virion and the peplomers were both active as antigens in the leucocyte migration inhibition, lymphocyte stimulation and skin hypersensitivity tests. The remaining virus material, freed of detergents used for virus disintegration and containing nucleocapsids, did not act as antigen in these tests of cell-mediated immunity."}
{"id": "PMID:194554", "title": "[Enzymomorphology of the vaccinal process in connection with formation of immunity to plague].", "content": "The studies conducted showed that the beginning of immunogenesis following the administration of live plague vaccine was preceded by a period of primary toxic action of multiplying microbes when the activity of a number of enzymes in the organs of guinea-pigs was temporarily reduced. Subsequently, inductive and productive phases of formation of antibodies started against the background of normalization and growth of the enzymatic activity associated with mobilization of energy. The earliest hyperplastic changes during immunogenesis occurred in the thymus-dependent areas of the lymphoid organs. Somewhat later, hyperplasia of B-structures dependent on the bone marrow started to prevail.", "contents": "[Enzymomorphology of the vaccinal process in connection with formation of immunity to plague]. The studies conducted showed that the beginning of immunogenesis following the administration of live plague vaccine was preceded by a period of primary toxic action of multiplying microbes when the activity of a number of enzymes in the organs of guinea-pigs was temporarily reduced. Subsequently, inductive and productive phases of formation of antibodies started against the background of normalization and growth of the enzymatic activity associated with mobilization of energy. The earliest hyperplastic changes during immunogenesis occurred in the thymus-dependent areas of the lymphoid organs. Somewhat later, hyperplasia of B-structures dependent on the bone marrow started to prevail."}
{"id": "PMID:194555", "title": "[Activity of different antigenic preparations from the retina to induce experimental auto-immune uveo-retinitis (EAU) in guinea pigs (author's transl)].", "content": "24 different antigenic preparations from bovine or guinea pig retina and 3 from bovine uvea were tested for their ability to induce uveo-retinitis in guinea pigs. Each animal received one injection into the hind foot pads of 0.1 ml og the tissue preparation mixed with an equal volume of complete Freund's adjuvant. The intensity of the disease was assessed by clinical and histological criteria. Homogenates and extracts from whole guinea pig retina are more active than the same preparations from bovine retina. Autologous retinal extract is slightly more active than homologous in low doses. In bovine retina, the autoantigen(s) is localized in the photoreceptor structures and the pigment epithelium. Bovine uveal preparations seem to be inactive when the epithelium has been removed. Purified outer segments are very active, as well as soluble extracts of outer segments. Highly purified bovine rhodopsin has no immunopathogenic activity. A soluble autoantigen (autoantigen S) has been isolated by preparative isoelectrofocusing from retinas of several species. Autoantigen S from guinea pig induces the disease in guinea pigs at a dose of a few micrograms.", "contents": "[Activity of different antigenic preparations from the retina to induce experimental auto-immune uveo-retinitis (EAU) in guinea pigs (author's transl)]. 24 different antigenic preparations from bovine or guinea pig retina and 3 from bovine uvea were tested for their ability to induce uveo-retinitis in guinea pigs. Each animal received one injection into the hind foot pads of 0.1 ml og the tissue preparation mixed with an equal volume of complete Freund's adjuvant. The intensity of the disease was assessed by clinical and histological criteria. Homogenates and extracts from whole guinea pig retina are more active than the same preparations from bovine retina. Autologous retinal extract is slightly more active than homologous in low doses. In bovine retina, the autoantigen(s) is localized in the photoreceptor structures and the pigment epithelium. Bovine uveal preparations seem to be inactive when the epithelium has been removed. Purified outer segments are very active, as well as soluble extracts of outer segments. Highly purified bovine rhodopsin has no immunopathogenic activity. A soluble autoantigen (autoantigen S) has been isolated by preparative isoelectrofocusing from retinas of several species. Autoantigen S from guinea pig induces the disease in guinea pigs at a dose of a few micrograms."}
{"id": "PMID:194558", "title": "[Relaps of a nasopharyngeal fibroma after 20 years (author's transl)].", "content": "In a 38 year old patient there was a relapse of a nasopharyngeal fibroma in the buccal mucous membrane which had been operatively removed from the nasopharynx 20 years ago. Both tumors were histologically identical. The patient did not suffer from hormonal disturbances.", "contents": "[Relaps of a nasopharyngeal fibroma after 20 years (author's transl)]. In a 38 year old patient there was a relapse of a nasopharyngeal fibroma in the buccal mucous membrane which had been operatively removed from the nasopharynx 20 years ago. Both tumors were histologically identical. The patient did not suffer from hormonal disturbances."}
{"id": "PMID:194559", "title": "Malignant disease in childhood: the problems in general practice.", "content": "The role of the family doctor with regard to malignant disease in childhood, can be summarized as follows: To act appropriately so that early diagnosis, which to an important degree determines the prognosis, is not delayed by a justifiably low index of suspicion. To assist the family, including the siblings, to cope with the severe emotional stress inherpent in the diagnosis of a malignancy in a child. To recognize the extreme danger of chicken pox and measles when contracted during chemotherapy, for cytotoxic drugs are also immune-suppressants, and appropriate immune globulins can be life-saving. To arrange for and cooperate in the support necessary when a child is nursed at home in the terminal stages.", "contents": "Malignant disease in childhood: the problems in general practice. The role of the family doctor with regard to malignant disease in childhood, can be summarized as follows: To act appropriately so that early diagnosis, which to an important degree determines the prognosis, is not delayed by a justifiably low index of suspicion. To assist the family, including the siblings, to cope with the severe emotional stress inherpent in the diagnosis of a malignancy in a child. To recognize the extreme danger of chicken pox and measles when contracted during chemotherapy, for cytotoxic drugs are also immune-suppressants, and appropriate immune globulins can be life-saving. To arrange for and cooperate in the support necessary when a child is nursed at home in the terminal stages."}
{"id": "PMID:194560", "title": "The role of adherent cells in the secondary cell-mediated response in vitro to a natural poxvirus pathogen.", "content": "The role of adherent cells in an in vitro secondary response to ectromelia virus infection was investigated. Spleen cells from ectromelia-primed mice (\"responder\" cells) depleted of adherent cells by either carbonyl iron treatment, adherence to plastic or passage through cotton wool columns had a markedly decreased capacity to produce a secondary response, as indicated by decreased T cell-mediated cytotoxicity against virus-infected target cells, when cultured with virus-infected \"stimulator\" cells. The secondary response was restored by the addition of peritoneal cells from either normal or ectromelia-immune mice. Small numbers of peritoneal cells completely reconstituted the response within a certain dose range but larger numbers produced a marked inhibition of the response. Spleen cells were less effective in restoring the response. The peritoneal cells were not merely acting as additional, infected \"stimulator\" or antigen-presenting cells, since they could be added as late as 3 days after culture. Reconstituting activity was not affected by pretreatment with anti-theta serum and complement and cell separation studies showed that the activity was associated mainly with Ig-negative cells and that the active cell probably bears Ia antigens on its surface. These results indicate that the adherent cells involved are probably macrophages and that they act non-specifically to produce optimum conditions for the specific response of T cells.", "contents": "The role of adherent cells in the secondary cell-mediated response in vitro to a natural poxvirus pathogen. The role of adherent cells in an in vitro secondary response to ectromelia virus infection was investigated. Spleen cells from ectromelia-primed mice (\"responder\" cells) depleted of adherent cells by either carbonyl iron treatment, adherence to plastic or passage through cotton wool columns had a markedly decreased capacity to produce a secondary response, as indicated by decreased T cell-mediated cytotoxicity against virus-infected target cells, when cultured with virus-infected \"stimulator\" cells. The secondary response was restored by the addition of peritoneal cells from either normal or ectromelia-immune mice. Small numbers of peritoneal cells completely reconstituted the response within a certain dose range but larger numbers produced a marked inhibition of the response. Spleen cells were less effective in restoring the response. The peritoneal cells were not merely acting as additional, infected \"stimulator\" or antigen-presenting cells, since they could be added as late as 3 days after culture. Reconstituting activity was not affected by pretreatment with anti-theta serum and complement and cell separation studies showed that the activity was associated mainly with Ig-negative cells and that the active cell probably bears Ia antigens on its surface. These results indicate that the adherent cells involved are probably macrophages and that they act non-specifically to produce optimum conditions for the specific response of T cells."}
{"id": "PMID:194561", "title": "Interrelationships of copper, cytochrome oxidase, phospholipid synthesis and adenine nucleotide binding.", "content": "Studies are reported on the interrelationships in liver mitochondria of copper status, cytochrome oxidase activity, adenine nucleotide binding capacity and phospholipid synthesis. Direct exposure of mitochondria to cyanide or diethyldithiocarbamate depressed cytochrome oxidase activity; ADP-binding and phospholipid synthesis. Fractionation of mitochondria to increase the specific activity of cytochrome oxidase about 10-fold did not increase the affinity to bind ADP. Ageing of mitochondria or dialysis of mitochondria or mitochondrial membrane preparations against water or diethyldithiocarbamate at 0--2 degrees for 18 h did not decrease cytochrome oxidase activity or copper content of reisolated and resuspended mitochondria or mitochondrial membrane preparations, but considerably reduced the affinity to bind ADP. The respiratory inhibitors, fluoride and azide, at concentrations inhibitory to cytochrome oxidase did not reduce ADP-binding or phospholipid synthesis. Atractyloside did not inhibit cytochrome oxidase activity but did inhibit ADP-binding and phospholipid synthesis. Pre-incubation of mitochondrial membrane preparations with Cu++ increased the copper content and ADP-binding affinity. The results indicate that cytochrome oxidase is not the ADP-binding site of the mitochondrial membrane system and that reduced cytochrome oxidase activity per se does not depress binding affinity. Copper appears to be a component of the adenine nucleotide binding sites of mitochondrial membranes because the copper-complexing agents, cyanide and diethyldithiocarbamate, depressed ADP-binding, while increased mitochondrial membrane copper content increased ADP-binding.", "contents": "Interrelationships of copper, cytochrome oxidase, phospholipid synthesis and adenine nucleotide binding. Studies are reported on the interrelationships in liver mitochondria of copper status, cytochrome oxidase activity, adenine nucleotide binding capacity and phospholipid synthesis. Direct exposure of mitochondria to cyanide or diethyldithiocarbamate depressed cytochrome oxidase activity; ADP-binding and phospholipid synthesis. Fractionation of mitochondria to increase the specific activity of cytochrome oxidase about 10-fold did not increase the affinity to bind ADP. Ageing of mitochondria or dialysis of mitochondria or mitochondrial membrane preparations against water or diethyldithiocarbamate at 0--2 degrees for 18 h did not decrease cytochrome oxidase activity or copper content of reisolated and resuspended mitochondria or mitochondrial membrane preparations, but considerably reduced the affinity to bind ADP. The respiratory inhibitors, fluoride and azide, at concentrations inhibitory to cytochrome oxidase did not reduce ADP-binding or phospholipid synthesis. Atractyloside did not inhibit cytochrome oxidase activity but did inhibit ADP-binding and phospholipid synthesis. Pre-incubation of mitochondrial membrane preparations with Cu++ increased the copper content and ADP-binding affinity. The results indicate that cytochrome oxidase is not the ADP-binding site of the mitochondrial membrane system and that reduced cytochrome oxidase activity per se does not depress binding affinity. Copper appears to be a component of the adenine nucleotide binding sites of mitochondrial membranes because the copper-complexing agents, cyanide and diethyldithiocarbamate, depressed ADP-binding, while increased mitochondrial membrane copper content increased ADP-binding."}
{"id": "PMID:194562", "title": "Watery diarrhoea syndrome with episodic hypercalcaemia.", "content": "A patient with the Watery-Diarrhoea syndrome and episodic hypercalcaemia is reported. Plasma levels of vasoactive intestinal peptide (VIP) were elevated, and an islet cell adenoma of the pancreas was removed following which VIP levels decreased and diarrhoea ceased. During a hypercalcaemic episode, serum parathyroid hormone (PTh) levels were suppressed indicating the hypercalcaemia was independent of PTh and probably due to a direct action of VIP on calcium turnover.", "contents": "Watery diarrhoea syndrome with episodic hypercalcaemia. A patient with the Watery-Diarrhoea syndrome and episodic hypercalcaemia is reported. Plasma levels of vasoactive intestinal peptide (VIP) were elevated, and an islet cell adenoma of the pancreas was removed following which VIP levels decreased and diarrhoea ceased. During a hypercalcaemic episode, serum parathyroid hormone (PTh) levels were suppressed indicating the hypercalcaemia was independent of PTh and probably due to a direct action of VIP on calcium turnover."}
{"id": "PMID:194564", "title": "Congenital cerebellar hypoplasia in jersey calves.", "content": "Congenital cerebellar hypoplasia and hydrocephalus is reported in 8 Jersey calves. The possible relationship between this entity and BVDMD virus is discussed.", "contents": "Congenital cerebellar hypoplasia in jersey calves. Congenital cerebellar hypoplasia and hydrocephalus is reported in 8 Jersey calves. The possible relationship between this entity and BVDMD virus is discussed."}
{"id": "PMID:194566", "title": "A fluorescent-antibody study of the pathogenesis of infectious laryngotracheitis.", "content": "A study of the pathogenesis of infectious laryngotracheitis (ILT) by the fluorescent-antibody (FA) technique in birds inoculated ocularly, intratracheally, by vent brush, and by aerosol revealed that the epithelium of the conjunctiva and respiratory tract are the tissues actively infected by natural routes of infection. The virus propagated at the sites of initial exposure but there was no evidence of spread by viremia. Viral antigen was detected 2-7 days postexposure and rarely thereafter. Birds infected intratracheally showed intense infection in the nasal turbinates, suggesting that high concentrations of virus were expelled as an aerosol from infected tracheas. Virus applied to the dorsal lip of the vent by drop or brush was rapidly transferred mechanically to the bursa of Fabricius; the epithelial lining between follicles and between follicular cortex and medulla was positive in FA tests 48-72 hours postexposure.", "contents": "A fluorescent-antibody study of the pathogenesis of infectious laryngotracheitis. A study of the pathogenesis of infectious laryngotracheitis (ILT) by the fluorescent-antibody (FA) technique in birds inoculated ocularly, intratracheally, by vent brush, and by aerosol revealed that the epithelium of the conjunctiva and respiratory tract are the tissues actively infected by natural routes of infection. The virus propagated at the sites of initial exposure but there was no evidence of spread by viremia. Viral antigen was detected 2-7 days postexposure and rarely thereafter. Birds infected intratracheally showed intense infection in the nasal turbinates, suggesting that high concentrations of virus were expelled as an aerosol from infected tracheas. Virus applied to the dorsal lip of the vent by drop or brush was rapidly transferred mechanically to the bursa of Fabricius; the epithelial lining between follicles and between follicular cortex and medulla was positive in FA tests 48-72 hours postexposure."}
{"id": "PMID:194567", "title": "Influence of environment on airsacculitis: effects of relative humidity and air temperature on broilers infected with Mycoplasma synoviae and infectious bronchitis.", "content": "Mycoplasma synoviae (MS) obtained from broiler chickens condemned for airsacculitis was used to determine the influence of air temperature and relative humidity on the severity of airsacculitis produced experimentally. Infectious bronchitis virus was administered to 3-week-old broilers 5 days before aerosol exposure to MS broth cultures, producing extensive airsacculitis within 21-day study periods. High (31-32 C), medium (19-24 C), and low (7-10 C) air temperatures were studied in conjection with high (75-90%), medium (38-56%), and low (23-26%) relative humidities. Airsacculitis was most extensive (45%) at low temperatures regradless of high or medium humidity. The incidence of airsacculitis was greater (39%) at low humidity than at high humidity (17%) when air temperatures were medium. At high temperature, the trend was toward more airsacculitis (12%) at high humidity than (5%) at low humidity. However, the effect of cold air temperature was more dominant than the effect of relative humidity.", "contents": "Influence of environment on airsacculitis: effects of relative humidity and air temperature on broilers infected with Mycoplasma synoviae and infectious bronchitis. Mycoplasma synoviae (MS) obtained from broiler chickens condemned for airsacculitis was used to determine the influence of air temperature and relative humidity on the severity of airsacculitis produced experimentally. Infectious bronchitis virus was administered to 3-week-old broilers 5 days before aerosol exposure to MS broth cultures, producing extensive airsacculitis within 21-day study periods. High (31-32 C), medium (19-24 C), and low (7-10 C) air temperatures were studied in conjection with high (75-90%), medium (38-56%), and low (23-26%) relative humidities. Airsacculitis was most extensive (45%) at low temperatures regradless of high or medium humidity. The incidence of airsacculitis was greater (39%) at low humidity than at high humidity (17%) when air temperatures were medium. At high temperature, the trend was toward more airsacculitis (12%) at high humidity than (5%) at low humidity. However, the effect of cold air temperature was more dominant than the effect of relative humidity."}
{"id": "PMID:194568", "title": "Pacheco's parrot disease of psittacine birds.", "content": "Pacheco's parrot disease was identified as the cause of death of 3 psittacine birds at an aviary. Confirming a previous report, a herpesvirus was found to be the etiologic agent. The virus induced mortality in embryonated chicken eggs and budgerigars. The virus was characterized by electron microscopy, filtration experiments, and ether-sensitivity. Hepatic lesions in chick embryos and budgerigars were similar by light- and electron-microscope studies. Naked and enveloped nucleocapsids were seen in the nucleus and cytoplasm of infected hepatocytes, and naked virions were present in the sinusoids of the liver. Multinucleated cells in the liver contained virus in both intranuclear and intracytoplasmic inclusions; the latter inclusions were both membrane-bound and not. Vaccination of budgerigars with a commercial lyophilized Marek's disease vaccine did not prevent infection with the Pacheco's disease herpesvirus.", "contents": "Pacheco's parrot disease of psittacine birds. Pacheco's parrot disease was identified as the cause of death of 3 psittacine birds at an aviary. Confirming a previous report, a herpesvirus was found to be the etiologic agent. The virus induced mortality in embryonated chicken eggs and budgerigars. The virus was characterized by electron microscopy, filtration experiments, and ether-sensitivity. Hepatic lesions in chick embryos and budgerigars were similar by light- and electron-microscope studies. Naked and enveloped nucleocapsids were seen in the nucleus and cytoplasm of infected hepatocytes, and naked virions were present in the sinusoids of the liver. Multinucleated cells in the liver contained virus in both intranuclear and intracytoplasmic inclusions; the latter inclusions were both membrane-bound and not. Vaccination of budgerigars with a commercial lyophilized Marek's disease vaccine did not prevent infection with the Pacheco's disease herpesvirus."}
{"id": "PMID:194569", "title": "Virus-neutralizing antibody titers against 8 avian adenovirus serotypes in breeder hens in Georgia by a microneutralization procedure.", "content": "Serums from 16 chicken-breeder flocks in Georgia were tested for virus-neutralizing antibody to 8 serotypes of avian adenovirus. Titers to all 8 serotypes were demonstrated in 8 of the flocks, titers to 7 in 6, and titers to fewer than 7 in the other 2 flocks. Although titers were high overall to some serotypes (types 2 and 8) and low to others (types 1, 4, and 5), with statistically significant differences between many titers, the data were difficult to interpret because of possible heterotypic responses of chickens infected with avian adeno-viruses. Used for titrations of serum antibody was a microneutralization procedure that is inexpensive. It proved also to provide reproducibility since titers from replicate tests differed by less than 3 twofold dilutions. In addition, there was a strong linear relation between titers obtained with the microneutralization procedure and a conventional plaque-assay titration procedure. The microneutralization procedure was less sensitive than the conventional procedure by a factor of about 5.5, but that was considered a disadvantage only with low-titered serums.", "contents": "Virus-neutralizing antibody titers against 8 avian adenovirus serotypes in breeder hens in Georgia by a microneutralization procedure. Serums from 16 chicken-breeder flocks in Georgia were tested for virus-neutralizing antibody to 8 serotypes of avian adenovirus. Titers to all 8 serotypes were demonstrated in 8 of the flocks, titers to 7 in 6, and titers to fewer than 7 in the other 2 flocks. Although titers were high overall to some serotypes (types 2 and 8) and low to others (types 1, 4, and 5), with statistically significant differences between many titers, the data were difficult to interpret because of possible heterotypic responses of chickens infected with avian adeno-viruses. Used for titrations of serum antibody was a microneutralization procedure that is inexpensive. It proved also to provide reproducibility since titers from replicate tests differed by less than 3 twofold dilutions. In addition, there was a strong linear relation between titers obtained with the microneutralization procedure and a conventional plaque-assay titration procedure. The microneutralization procedure was less sensitive than the conventional procedure by a factor of about 5.5, but that was considered a disadvantage only with low-titered serums."}
{"id": "PMID:194570", "title": "The pathology of necrotic enteritis of chickens following infusion of broth cultures of Clostridium perfringens into the duodenum.", "content": "Necrotic enteritis was consistently reproduced when enough active broth culture of Clostridium perfringens type A was infused intraduodenally. Typical lesions of necrotic enteritis were seen as early as 5 hr after infusion was begun. The histologic lesions observed at 1 hr were characterized by edema in the lamina propria and desquamation of epithelial cells. Large numbers of clostridia were seen among these sloughed cells. Coagulation necrosis of the tips of villi became evident at 3 hr and was marked at 5 hr. Many clumps of clostridia were obvious among the necrotic tissue. At 8 and 12 hr the necrotic lesions extended to involve most of the villus structures. Morphologically abnormal erythrocytes were evident in the visceral organs at 12 hr.", "contents": "The pathology of necrotic enteritis of chickens following infusion of broth cultures of Clostridium perfringens into the duodenum. Necrotic enteritis was consistently reproduced when enough active broth culture of Clostridium perfringens type A was infused intraduodenally. Typical lesions of necrotic enteritis were seen as early as 5 hr after infusion was begun. The histologic lesions observed at 1 hr were characterized by edema in the lamina propria and desquamation of epithelial cells. Large numbers of clostridia were seen among these sloughed cells. Coagulation necrosis of the tips of villi became evident at 3 hr and was marked at 5 hr. Many clumps of clostridia were obvious among the necrotic tissue. At 8 and 12 hr the necrotic lesions extended to involve most of the villus structures. Morphologically abnormal erythrocytes were evident in the visceral organs at 12 hr."}
{"id": "PMID:194571", "title": "The pathology of necrotic enteritis of chickens following infusion of crude toxins of Clostridium perfringens into the duodenum.", "content": "Necrotic enteritis was produced in 4-week-old chickens with bacteria-free crude toxins of Clostridium perfringens. Typical gross lesions could be seen as early as 3 hr after intraduodenal infusion of toxin was begun. Early microscopic lesions were observed at 20 minutes, progressing with time to involve most of the mucosa. Death was related to the amount of toxin administered. Because systemic absorption of toxin is likely, acutely affected birds may die from toxemia.", "contents": "The pathology of necrotic enteritis of chickens following infusion of crude toxins of Clostridium perfringens into the duodenum. Necrotic enteritis was produced in 4-week-old chickens with bacteria-free crude toxins of Clostridium perfringens. Typical gross lesions could be seen as early as 3 hr after intraduodenal infusion of toxin was begun. Early microscopic lesions were observed at 20 minutes, progressing with time to involve most of the mucosa. Death was related to the amount of toxin administered. Because systemic absorption of toxin is likely, acutely affected birds may die from toxemia."}
{"id": "PMID:194572", "title": "The interaction of Clostridium perfringens and its toxins in the production of necrotic enteritis of chickens.", "content": "The intraduodenal administration of large numbers of Clostridium perfringens cells harvested from broth cultures and resuspended in PBS or fresh sterile thioglycollate broth produced a very mild form of necrotic enteritis. Administering an appropriate number of cells in culture supernatant, however, produced typical field-type disease. Alpha toxin was shown to be the significant toxin recoverable from broth-culture supernatant fluids. Requirements to produce the disease are minor intestinal damage and sufficient numbers of toxigenic C. perfringens in the intestine.", "contents": "The interaction of Clostridium perfringens and its toxins in the production of necrotic enteritis of chickens. The intraduodenal administration of large numbers of Clostridium perfringens cells harvested from broth cultures and resuspended in PBS or fresh sterile thioglycollate broth produced a very mild form of necrotic enteritis. Administering an appropriate number of cells in culture supernatant, however, produced typical field-type disease. Alpha toxin was shown to be the significant toxin recoverable from broth-culture supernatant fluids. Requirements to produce the disease are minor intestinal damage and sufficient numbers of toxigenic C. perfringens in the intestine."}
{"id": "PMID:194573", "title": "Preparation of antisera to group-specific antigens of avian leukosis-sarcoma viruses: an alternate approach.", "content": "Immunization of rabbits with a pooled preparation of chromato-graphically purified avian myeloblastosis virus (AMV) group-specific (gs) antigens produced relatively large volumes of antiserum that was as broadly reactive in complement-fixation (CF) tests as antiserum produced in hamsters with tumors induced by Rous sarcoma virus. This alternate procedure should be of value for routine preparation of leukosis virus gs antiserum. Other antisera prepared against disrupted AMV had spurious reactivities that confused CF testing of embryos and tissue extracts. This artifact was attributed to the high affinity of serum albumin for AMV virions and the resultant production of antibodies when plasma-derived AMV was used as immunogen. A high-molecular-weight AMV CF antigen was also found in early fractions eluted from an agarose-gel column.", "contents": "Preparation of antisera to group-specific antigens of avian leukosis-sarcoma viruses: an alternate approach. Immunization of rabbits with a pooled preparation of chromato-graphically purified avian myeloblastosis virus (AMV) group-specific (gs) antigens produced relatively large volumes of antiserum that was as broadly reactive in complement-fixation (CF) tests as antiserum produced in hamsters with tumors induced by Rous sarcoma virus. This alternate procedure should be of value for routine preparation of leukosis virus gs antiserum. Other antisera prepared against disrupted AMV had spurious reactivities that confused CF testing of embryos and tissue extracts. This artifact was attributed to the high affinity of serum albumin for AMV virions and the resultant production of antibodies when plasma-derived AMV was used as immunogen. A high-molecular-weight AMV CF antigen was also found in early fractions eluted from an agarose-gel column."}
{"id": "PMID:194577", "title": "Adenylate cyclase activity in lymphocyte subcellular fractions. Characterization of non-nuclear adenylate cyclase.", "content": "Human peripheral lymphocytes were broken in a Dounce homogenizer and subcellular fractions enriched in plasma membranes or microsomal particles and mitochondria were isolated by centrifugation through a discontinuous sucrose gradient. Various agents that promote cyclic AMP accumulation in intact lymphocytes were compared in their ability to stimulate adenylate cyclase activity in the individual fractions. Plasma-membrane-rich fractions that were essentially free of other subcellular particles as judged by electron microscopy and marker enzyme measurements responded to fluoride, but weakly or not at all to prostaglandin E1 and other prostaglandins. Microsomal and mitochondrial-rich fractions responded markedly to both prostaglandin E1 and fluoride. In some, but not all, experiments phytohaemagglutinin produced a modest increase in enzyme activity in plasma-membrane-rich fractions. Catecholamines, histamine, parathyrin, glucagon and corticotropin produced little or no response. In the absence of theophylline, adenosine (1-10 micronM) stimulated basal enzyme activity, although at higher concentrations the responses to prostaglandin E1 and fluoride were inhibited. GTP (1-100 micronM) and GMP(5-1000 micronM) respectively inhibited or stimulated the response to fluoride, whereas the converse was true with prostaglandin E1.", "contents": "Adenylate cyclase activity in lymphocyte subcellular fractions. Characterization of non-nuclear adenylate cyclase. Human peripheral lymphocytes were broken in a Dounce homogenizer and subcellular fractions enriched in plasma membranes or microsomal particles and mitochondria were isolated by centrifugation through a discontinuous sucrose gradient. Various agents that promote cyclic AMP accumulation in intact lymphocytes were compared in their ability to stimulate adenylate cyclase activity in the individual fractions. Plasma-membrane-rich fractions that were essentially free of other subcellular particles as judged by electron microscopy and marker enzyme measurements responded to fluoride, but weakly or not at all to prostaglandin E1 and other prostaglandins. Microsomal and mitochondrial-rich fractions responded markedly to both prostaglandin E1 and fluoride. In some, but not all, experiments phytohaemagglutinin produced a modest increase in enzyme activity in plasma-membrane-rich fractions. Catecholamines, histamine, parathyrin, glucagon and corticotropin produced little or no response. In the absence of theophylline, adenosine (1-10 micronM) stimulated basal enzyme activity, although at higher concentrations the responses to prostaglandin E1 and fluoride were inhibited. GTP (1-100 micronM) and GMP(5-1000 micronM) respectively inhibited or stimulated the response to fluoride, whereas the converse was true with prostaglandin E1."}
{"id": "PMID:194574", "title": "Use of polyethylene glycol and fluorocarbon for the purification of avian encephalomyelitis virus.", "content": "A simple method is described for isolating avian encephalomyelitis virus (AEV) from a bulk amount of proteins and lipids in a homogenate of infected whole chicken embryos. More than 90% of the virus in the homogenate was precipitated by 4% polyethylene glycol (PEG), and the precipitate was free of approximately 90% of the total nonviral protein. When the homogenate was extracted with fluorocarbon, the aqueous fraction retained the full virus infectivity and about 70% of the protein but was free from most lipid materials. A two-step procedure (precipitation of the homogenate by 4% PEG, followed by extraction of the precipitate by fluorocarbon) gave a 50-fold purification of AEV over the original homogenate. The procedure is simple, rapid, and effective in removing nonviral proteins and lipids from host tissues. It is useful as an initial treatment of embryonic materials for the purification of AEV.", "contents": "Use of polyethylene glycol and fluorocarbon for the purification of avian encephalomyelitis virus. A simple method is described for isolating avian encephalomyelitis virus (AEV) from a bulk amount of proteins and lipids in a homogenate of infected whole chicken embryos. More than 90% of the virus in the homogenate was precipitated by 4% polyethylene glycol (PEG), and the precipitate was free of approximately 90% of the total nonviral protein. When the homogenate was extracted with fluorocarbon, the aqueous fraction retained the full virus infectivity and about 70% of the protein but was free from most lipid materials. A two-step procedure (precipitation of the homogenate by 4% PEG, followed by extraction of the precipitate by fluorocarbon) gave a 50-fold purification of AEV over the original homogenate. The procedure is simple, rapid, and effective in removing nonviral proteins and lipids from host tissues. It is useful as an initial treatment of embryonic materials for the purification of AEV."}
{"id": "PMID:194578", "title": "Adenylate cyclase activity in lymphocyte subcellular fractions. Characterization of a nuclear adenylate cyclase.", "content": "Nuclei from purified human peripheral lymphocytes were prepared by incubations with Triton X-100 to disrupt the cells, followed by sucrose-density gradient centrifugation. The nuclei were pure as judged by phase-contrast microscopy and had low contents of non-nuclear marker enzymes. In addition, nuclei prepared from lymphocytes surface-labelled with 125I had only 2-7% of the radioactivity bound to intact lymphocytes. At 3.3 mM-Ca2+ and 100 micronM-ATP a fluoride-sensitive adenylate cyclase was demonstrated in nuclei prepared in 0.2% Triton X-100 or 0.33% Triton X-100. There was linear accumulation of cyclic AMP for 10 min in both preparations. The apparent Km for ATP was 90 micronM. Adenylate cyclase activity was augmented by 1.0 mM-Mn2+ and inhibited at higher concentrations. Ca2+ showed two peaks of stimulation, at 1.0-2.5 mM- and above 10 mM-Ca2+. Mg2+ was inhibitory at all concentrations. EDTA OR EGTA only slightly decreased adenylate cyclase activity, suggesting that another metal ion may be necessary for activity. Adenylate cyclase activity was stimulated by 10mM-isoproterenol and 10 micronM-adrenaline in the presence of a phosphodiesterase inhibitor. Phytohaemagglutinin and prostaglandin E1 alone or in combination with isoproterenol had no effect on nuclear adenylate cyclase activity in either nuclei preparation. These results indicate that human lymphocyte nuclei contain one or several adenylate cyclases which differ from adenylate cyclases found in other subcellular fractions of these cells with regard to their bivalentcation requirements and responsiveness to pharmacological agents.", "contents": "Adenylate cyclase activity in lymphocyte subcellular fractions. Characterization of a nuclear adenylate cyclase. Nuclei from purified human peripheral lymphocytes were prepared by incubations with Triton X-100 to disrupt the cells, followed by sucrose-density gradient centrifugation. The nuclei were pure as judged by phase-contrast microscopy and had low contents of non-nuclear marker enzymes. In addition, nuclei prepared from lymphocytes surface-labelled with 125I had only 2-7% of the radioactivity bound to intact lymphocytes. At 3.3 mM-Ca2+ and 100 micronM-ATP a fluoride-sensitive adenylate cyclase was demonstrated in nuclei prepared in 0.2% Triton X-100 or 0.33% Triton X-100. There was linear accumulation of cyclic AMP for 10 min in both preparations. The apparent Km for ATP was 90 micronM. Adenylate cyclase activity was augmented by 1.0 mM-Mn2+ and inhibited at higher concentrations. Ca2+ showed two peaks of stimulation, at 1.0-2.5 mM- and above 10 mM-Ca2+. Mg2+ was inhibitory at all concentrations. EDTA OR EGTA only slightly decreased adenylate cyclase activity, suggesting that another metal ion may be necessary for activity. Adenylate cyclase activity was stimulated by 10mM-isoproterenol and 10 micronM-adrenaline in the presence of a phosphodiesterase inhibitor. Phytohaemagglutinin and prostaglandin E1 alone or in combination with isoproterenol had no effect on nuclear adenylate cyclase activity in either nuclei preparation. These results indicate that human lymphocyte nuclei contain one or several adenylate cyclases which differ from adenylate cyclases found in other subcellular fractions of these cells with regard to their bivalentcation requirements and responsiveness to pharmacological agents."}
{"id": "PMID:194579", "title": "Effects of adenosine 3':5'-cyclic monophosphate and serum on synthesis of hyaluronic acid in confluent rat fibroblasts.", "content": "A small amount of hyaluronic acid is synthesized in confluent cultures of rat fibroblasts, which have a high content of cyclic AMP. Addition of calf serum caused a rapid decrease in the cellular cyclic AMP content and large increases in hyaluronic acid synthetase activity and hyaluronic acid production. Addition of cyclic AMP also caused a marked increase in hyaluronic acid synthetase activity within 2h and then increased hyaluronic acid production. The effects of cyclic AMP and serum on hyaluronic acid synthesis were additive. Prostaglandin E2, which increased the cyclic AMP by stimulating adenylate cyclase, was as effective as cyclic AMP in increasing hyaluronic acid synthetase activity, but AMP was far less effective than cyclic AMP. These results indicate that cyclic AMP itself stimulates the mucopolysaccharide synthesis and that the effect of serum is not due to a decrease in cyclic AMP in the cells.", "contents": "Effects of adenosine 3':5'-cyclic monophosphate and serum on synthesis of hyaluronic acid in confluent rat fibroblasts. A small amount of hyaluronic acid is synthesized in confluent cultures of rat fibroblasts, which have a high content of cyclic AMP. Addition of calf serum caused a rapid decrease in the cellular cyclic AMP content and large increases in hyaluronic acid synthetase activity and hyaluronic acid production. Addition of cyclic AMP also caused a marked increase in hyaluronic acid synthetase activity within 2h and then increased hyaluronic acid production. The effects of cyclic AMP and serum on hyaluronic acid synthesis were additive. Prostaglandin E2, which increased the cyclic AMP by stimulating adenylate cyclase, was as effective as cyclic AMP in increasing hyaluronic acid synthetase activity, but AMP was far less effective than cyclic AMP. These results indicate that cyclic AMP itself stimulates the mucopolysaccharide synthesis and that the effect of serum is not due to a decrease in cyclic AMP in the cells."}
{"id": "PMID:194580", "title": "Effects of glucose, glucose metabolites and calcium ions on adenylate cyclase activity in homogenates of mouse pancreatic islets.", "content": "The effects of glucose, a series of glucose metabolites, nicotinamide nucleotides, Ca2+ and p-chloromercuribenzenesulphonate on adenylate cyclase activity in homogenates of mouse pancreatic islets were studied. The basal activity of the adenylate cyclase was approx. 6 pmol of cyclic AMP formed/30 min per microng of DNA at 30 degrees C. The enzyme activity was stimulated by some 150% by fluoride. Starvation of the animals for 48h had no effect on either the basal or the fluoride-stimulated activity. The adenylate cyclase activity was increased by 40-50% when 17 mM-glucose, 10 micronM-phosphoenolpyruvate or 10 micronM-pyruvate was added to the assay medium. The effect of glucose was unchanged in the presence of 17 mM-mannoheptulose, and mannoheptulose alone had no effect. The other glycolytic intermediates, and the coenzymes NAD+, NADH and NADPH, at concentrations up to 1 mM were without any detectable effect on the rate of formation of cyclic AMP. The insulin secretagogue p-chloromercuribenzenesulphonate inhibited the adenylate cyclase markedly even at a concentration of 10 micronM. Calculated concentrations of free Ca2+ of 10 micronM and 0.1 mM inhibited adenylate cyclase by 29 and 71% respectively. It is concluded that both glucose itself and phosphoenolpyruvate and/or pyruvate are true activating ligands for islet and adenylate cyclase and that inhibition of the cyclase by Ca2+ may be of physiological significance.", "contents": "Effects of glucose, glucose metabolites and calcium ions on adenylate cyclase activity in homogenates of mouse pancreatic islets. The effects of glucose, a series of glucose metabolites, nicotinamide nucleotides, Ca2+ and p-chloromercuribenzenesulphonate on adenylate cyclase activity in homogenates of mouse pancreatic islets were studied. The basal activity of the adenylate cyclase was approx. 6 pmol of cyclic AMP formed/30 min per microng of DNA at 30 degrees C. The enzyme activity was stimulated by some 150% by fluoride. Starvation of the animals for 48h had no effect on either the basal or the fluoride-stimulated activity. The adenylate cyclase activity was increased by 40-50% when 17 mM-glucose, 10 micronM-phosphoenolpyruvate or 10 micronM-pyruvate was added to the assay medium. The effect of glucose was unchanged in the presence of 17 mM-mannoheptulose, and mannoheptulose alone had no effect. The other glycolytic intermediates, and the coenzymes NAD+, NADH and NADPH, at concentrations up to 1 mM were without any detectable effect on the rate of formation of cyclic AMP. The insulin secretagogue p-chloromercuribenzenesulphonate inhibited the adenylate cyclase markedly even at a concentration of 10 micronM. Calculated concentrations of free Ca2+ of 10 micronM and 0.1 mM inhibited adenylate cyclase by 29 and 71% respectively. It is concluded that both glucose itself and phosphoenolpyruvate and/or pyruvate are true activating ligands for islet and adenylate cyclase and that inhibition of the cyclase by Ca2+ may be of physiological significance."}
{"id": "PMID:194581", "title": "The appearance of gluconeogenesis at birth in sheep. Activation of the pathway associated with blood oxygenation.", "content": "1. Measurements of pyruvate carboxylase, mitochondrial phosphoenolpyruvate carboxykinase (GTP), hexose bisphosphatase and glucose 6-phosphatase in developing sheep liver showed substantial activities of all enzymes in the foetus, especially towards the end of gestation. Cytosol phosphoenolpyruvate carboxykinase (GTP) in livers of mid-term foetuses was only 10% of the activity at birth. 2. All enzymes except pyruvate carboxylase showed 1.5-2-fold increases after birth. 3. Gluconeogenesis form [14C]actate could not be detected in chronically cannulated sheep foetuses at any developmental stage and was not initiated by the infusion of adrenaline or glucagon. 4. An active pathway of gluconeogenesis was evident in vivo within 2 min after natural birth or within 4 min after Caesarian delivery of term lambs, and was delayed in prematurely delivered lambs until breathing was established and the blood fully oxygenated. 5. It is proposed that oxygen availability initiates gluconeogenesis in the newborn lamb.", "contents": "The appearance of gluconeogenesis at birth in sheep. Activation of the pathway associated with blood oxygenation. 1. Measurements of pyruvate carboxylase, mitochondrial phosphoenolpyruvate carboxykinase (GTP), hexose bisphosphatase and glucose 6-phosphatase in developing sheep liver showed substantial activities of all enzymes in the foetus, especially towards the end of gestation. Cytosol phosphoenolpyruvate carboxykinase (GTP) in livers of mid-term foetuses was only 10% of the activity at birth. 2. All enzymes except pyruvate carboxylase showed 1.5-2-fold increases after birth. 3. Gluconeogenesis form [14C]actate could not be detected in chronically cannulated sheep foetuses at any developmental stage and was not initiated by the infusion of adrenaline or glucagon. 4. An active pathway of gluconeogenesis was evident in vivo within 2 min after natural birth or within 4 min after Caesarian delivery of term lambs, and was delayed in prematurely delivered lambs until breathing was established and the blood fully oxygenated. 5. It is proposed that oxygen availability initiates gluconeogenesis in the newborn lamb."}
{"id": "PMID:194582", "title": "Some properties of aldehyde dehydrogenase from sheep liver mitochondria.", "content": "Aldehyde dehydrogenase from sheep liver mitochondria was purified to homogeneity as judged by electrophoresis on polyacrylamide gels, and by sedimentation-equilibrium experiments in the analytical ultracentrifuge. The enzyme has a molecular weight of 198000 and a subunit size of 48000, indicating that the molecule is a tetramer. Fluorescence and spectrophotometric titrations indicate that each subunit can bind 1 molecule of NADH. Enzymic activity is completely blocked by reaction of 4mol of 5,5'-dithiobis-(2-nitrobenzoate)/mol of enzyme. Excess of disulfiram or iodoacetamide decreases activity to only 50% of the control value, and only two thiol groups per molecule are apparently modified by these reagents.", "contents": "Some properties of aldehyde dehydrogenase from sheep liver mitochondria. Aldehyde dehydrogenase from sheep liver mitochondria was purified to homogeneity as judged by electrophoresis on polyacrylamide gels, and by sedimentation-equilibrium experiments in the analytical ultracentrifuge. The enzyme has a molecular weight of 198000 and a subunit size of 48000, indicating that the molecule is a tetramer. Fluorescence and spectrophotometric titrations indicate that each subunit can bind 1 molecule of NADH. Enzymic activity is completely blocked by reaction of 4mol of 5,5'-dithiobis-(2-nitrobenzoate)/mol of enzyme. Excess of disulfiram or iodoacetamide decreases activity to only 50% of the control value, and only two thiol groups per molecule are apparently modified by these reagents."}
{"id": "PMID:194583", "title": "The allosteric mechanism of bovine liver glutamate dehydrogenase. Evidence from circular-dichroism studies for a conformational change in the ternary complex enzyme-(oxidized nicotinamide-adenine dinucleotide)-glutarate.", "content": "1. Computer averaging of multiple scans was used to refine the circular dichroism spectrum of bovine liver glutamate dehydrogenase, revealing well-defined structure in the aromatic region. 2. The circular dichroism of NAD+ bound to glutamate dehydrogenase is strongly negative at 260nm, probably owing to immobilization of the adenosine moiety. Loss of the characteristic adenine-nicotinamide interaction suggests that the coenzyme is bound in an unstacked conformation. 3. Glutarate and succinate, substrate analogues that are both inhibitors competitive with glutamate, do not significantly perturb the circular-dichroism spectrum of the enzyme in the absence of NAD+. 4. In the presence of NAD+, 150nM-succinate decreases the negative circular dichroism corresponding to bound coenzyme, but does not affect the protein circular dichroism. However, ISOmM-glutarate causes profound alternations of the circular-dichroism spectra of the bound NAD+ and of the enzyme, indicative of a protein conformational change. This direct evidence of conformational change specifically promoted by C5 dicarboxylates confirms the previous inference from protection studies. 5. The conformational change is discussed in relation to the allosteric mechanism of glutamate dehydrogenase.", "contents": "The allosteric mechanism of bovine liver glutamate dehydrogenase. Evidence from circular-dichroism studies for a conformational change in the ternary complex enzyme-(oxidized nicotinamide-adenine dinucleotide)-glutarate. 1. Computer averaging of multiple scans was used to refine the circular dichroism spectrum of bovine liver glutamate dehydrogenase, revealing well-defined structure in the aromatic region. 2. The circular dichroism of NAD+ bound to glutamate dehydrogenase is strongly negative at 260nm, probably owing to immobilization of the adenosine moiety. Loss of the characteristic adenine-nicotinamide interaction suggests that the coenzyme is bound in an unstacked conformation. 3. Glutarate and succinate, substrate analogues that are both inhibitors competitive with glutamate, do not significantly perturb the circular-dichroism spectrum of the enzyme in the absence of NAD+. 4. In the presence of NAD+, 150nM-succinate decreases the negative circular dichroism corresponding to bound coenzyme, but does not affect the protein circular dichroism. However, ISOmM-glutarate causes profound alternations of the circular-dichroism spectra of the bound NAD+ and of the enzyme, indicative of a protein conformational change. This direct evidence of conformational change specifically promoted by C5 dicarboxylates confirms the previous inference from protection studies. 5. The conformational change is discussed in relation to the allosteric mechanism of glutamate dehydrogenase."}
{"id": "PMID:194584", "title": "Evidence that latent collagenases are enzyme-inhibitor complexes.", "content": "Specific collagenase from the culture media of various rabbit tissues and cells exists in active and latent forms. Latent collagenase is most effectively activated with 4-aminophenylmercuric acetate, a thiol-blocking reagent, strongly suggesting that latent forms are enzyme-inhibitor complexes. A collagenase inhibitor from bone cultures, which may be closely related to the inhibitor of such latent enzyme complexes, was partially characterized.", "contents": "Evidence that latent collagenases are enzyme-inhibitor complexes. Specific collagenase from the culture media of various rabbit tissues and cells exists in active and latent forms. Latent collagenase is most effectively activated with 4-aminophenylmercuric acetate, a thiol-blocking reagent, strongly suggesting that latent forms are enzyme-inhibitor complexes. A collagenase inhibitor from bone cultures, which may be closely related to the inhibitor of such latent enzyme complexes, was partially characterized."}
{"id": "PMID:194585", "title": "The amino acid sequence of cytochrome c from the locust, Schistocerca gregaria Forskal.", "content": "The amino acid sequence of locust cytochrome c was determined, although the overlap between chymotryptic and tryptic peptides at residues tyrosine-97 and leucine-98 was not observed, owing to an anomalous tryptic break duplicating the chymotryptic digestion. The molecule consists of a single polypeptide chain of 107 residues, homologous with other mitochondrial cytochromes c. In common with other known insect cytochromes c, it possesses a non-acetylated, four-residue tail at the N-terminus relative to glycine-1 of the standard alignment. A molecular phylogeny for 17 species was constructed relating the cytochrome c molecules of Schistocerca gregaria and other invertebrates with those of representative taxonomic groups. Experimental details are given in a supplementary paper deposited as Supplementary Publication SUP 50077 (24 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can obtained on the terms indicated in Biochem. J. (1977) 161, 1.", "contents": "The amino acid sequence of cytochrome c from the locust, Schistocerca gregaria Forskal. The amino acid sequence of locust cytochrome c was determined, although the overlap between chymotryptic and tryptic peptides at residues tyrosine-97 and leucine-98 was not observed, owing to an anomalous tryptic break duplicating the chymotryptic digestion. The molecule consists of a single polypeptide chain of 107 residues, homologous with other mitochondrial cytochromes c. In common with other known insect cytochromes c, it possesses a non-acetylated, four-residue tail at the N-terminus relative to glycine-1 of the standard alignment. A molecular phylogeny for 17 species was constructed relating the cytochrome c molecules of Schistocerca gregaria and other invertebrates with those of representative taxonomic groups. Experimental details are given in a supplementary paper deposited as Supplementary Publication SUP 50077 (24 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can obtained on the terms indicated in Biochem. J. (1977) 161, 1."}
{"id": "PMID:194604", "title": "The influence of the calcium antagonist fendiline on tone and motility of the guinea pig gut smooth muscle and the cAMP and cGMP concentrations of the isolated terminal ileum.", "content": "In various parts of the guinea pig gastrointestinal tract the calcium antagonist N-(2-benzhydryl-ethyl)-N-(1-phenyl-ethyl)-amine hydrochloride (fendiline, Sensit) decreases the smooth muscle tone elevated by K+-induced depolarisation. This effect is antagonized by addition of extra-Ca++. The muscle relaxation is dos-dependent and amounts to 45-90% after 1-5 microng/ml fendiline. Proportionally to this effect the tissue concentration in cGMP is decreased whereas cAMP remains unchanged. After 54 micron/ml theophylline the cAMP level in the terminal ileum is increased significantly whereas cGMP does not change. Theophylline has no influence on the relaxing effect of 1 microng/ml fendiline. By contrast, the increase in cAMP after theophylline is prevented by fendiline. These findings are explained by the antagonistic effect of fendiline to Ca++, which activates the guanylate cyclase and inhibits the adenylate cyclase. Furthermore, fendiline seems to prevent the binding of theophylline to guinea pig ileal phosphodiesterase. It is discussed that cGMP plays a physiological role in controlling the intestinal smolth muscle tone and motility.", "contents": "The influence of the calcium antagonist fendiline on tone and motility of the guinea pig gut smooth muscle and the cAMP and cGMP concentrations of the isolated terminal ileum. In various parts of the guinea pig gastrointestinal tract the calcium antagonist N-(2-benzhydryl-ethyl)-N-(1-phenyl-ethyl)-amine hydrochloride (fendiline, Sensit) decreases the smooth muscle tone elevated by K+-induced depolarisation. This effect is antagonized by addition of extra-Ca++. The muscle relaxation is dos-dependent and amounts to 45-90% after 1-5 microng/ml fendiline. Proportionally to this effect the tissue concentration in cGMP is decreased whereas cAMP remains unchanged. After 54 micron/ml theophylline the cAMP level in the terminal ileum is increased significantly whereas cGMP does not change. Theophylline has no influence on the relaxing effect of 1 microng/ml fendiline. By contrast, the increase in cAMP after theophylline is prevented by fendiline. These findings are explained by the antagonistic effect of fendiline to Ca++, which activates the guanylate cyclase and inhibits the adenylate cyclase. Furthermore, fendiline seems to prevent the binding of theophylline to guinea pig ileal phosphodiesterase. It is discussed that cGMP plays a physiological role in controlling the intestinal smolth muscle tone and motility."}
{"id": "PMID:194605", "title": "Changes in muscle action potentials of patients with diseases of motor units following the infusion of a peptide fragment of ACTH.", "content": "The polypeptides ACTH and ATCH4-10 (OI 63) witha sequence of amino acids H-Met-Glu-His-Phe-Arg-Trp-Gly-OH, have similar stimulating effects  on motor units in lower mammals. Their actions differ primarily in that ACTH4-10 is not corticotropic. Since the corticotropic action of ACTH frequently presents a problem during its clinical use in treatment of motor unit diseases, the action of ACTH4-10 was studied in two patients with muscular atrophy. Prior to administration of ACTH4-10, stimulation of M. oppenens pollicis through the median nerve evoked muscle action potentials in both patients which progressively declined in amplitude. This decline was not observed subsequent to the infuscion of ACTH4-10 (3, 6 and 15 mg). The effect lasted partially in excess of at least 2 h. It is suggested that ACTH4-10 produces this effect by direct action on a peripheral component of the motor unit and/or indirectly by an action on the central nervous system.", "contents": "Changes in muscle action potentials of patients with diseases of motor units following the infusion of a peptide fragment of ACTH. The polypeptides ACTH and ATCH4-10 (OI 63) witha sequence of amino acids H-Met-Glu-His-Phe-Arg-Trp-Gly-OH, have similar stimulating effects  on motor units in lower mammals. Their actions differ primarily in that ACTH4-10 is not corticotropic. Since the corticotropic action of ACTH frequently presents a problem during its clinical use in treatment of motor unit diseases, the action of ACTH4-10 was studied in two patients with muscular atrophy. Prior to administration of ACTH4-10, stimulation of M. oppenens pollicis through the median nerve evoked muscle action potentials in both patients which progressively declined in amplitude. This decline was not observed subsequent to the infuscion of ACTH4-10 (3, 6 and 15 mg). The effect lasted partially in excess of at least 2 h. It is suggested that ACTH4-10 produces this effect by direct action on a peripheral component of the motor unit and/or indirectly by an action on the central nervous system."}
{"id": "PMID:194606", "title": "Effect of vinblastine on rat liver ultrastructure.", "content": "A single injection of vinblastine given i.v. to rats lead to the disappearance of microtubules, development of crystalline inclusions, dilation of Golgi sacculi, formation of multivesicular bodies and cytosegresomes as well as accumulation of lysosomes in the cytoplasm of liver cells. The endoplasmic reticulum and mitochondria do not seem to be affected. The question of whether or not these fine structural alterations are causally related has yet to be elucidated.", "contents": "Effect of vinblastine on rat liver ultrastructure. A single injection of vinblastine given i.v. to rats lead to the disappearance of microtubules, development of crystalline inclusions, dilation of Golgi sacculi, formation of multivesicular bodies and cytosegresomes as well as accumulation of lysosomes in the cytoplasm of liver cells. The endoplasmic reticulum and mitochondria do not seem to be affected. The question of whether or not these fine structural alterations are causally related has yet to be elucidated."}
{"id": "PMID:194607", "title": "[The immune response of the fetus in the diagnosis of intrauterine infections: IgM and IgA concentrations in the umbilical cord blood and titers of rubella and cytomegalic virus antibodies].", "content": "Two serological methods, hemagglutination and complement fixation, have been used respectively to determine HAI titers to rubella virus and C fixing antibodies to cytomegalovirus in cord blood of newborn infants delivered in Turin from August 1973 to April 1974. Sera have been divided according to antibody titer and aspecific IgM and IgA concentrations. By statistical analysis we observed a highly significant association between both IgM and IgA concentration and antibody titers to rubella virus.", "contents": "[The immune response of the fetus in the diagnosis of intrauterine infections: IgM and IgA concentrations in the umbilical cord blood and titers of rubella and cytomegalic virus antibodies]. Two serological methods, hemagglutination and complement fixation, have been used respectively to determine HAI titers to rubella virus and C fixing antibodies to cytomegalovirus in cord blood of newborn infants delivered in Turin from August 1973 to April 1974. Sera have been divided according to antibody titer and aspecific IgM and IgA concentrations. By statistical analysis we observed a highly significant association between both IgM and IgA concentration and antibody titers to rubella virus."}
{"id": "PMID:194613", "title": "Neuromuscular facilitation during train-of-four and tetanic stimulation in healthy volunteers: observations with half-refractory paired responses.", "content": "The compound electromyographic response of the thenar musculature was elicited by supramaximal stimulation of the ulnar nerve in 12 awake healthy volunteers. The half-refractory period of the neuromuscular transmission was determined. Twin stimuli separated by the half-refractory interval were repeated as a unit at 2 Hz and at 50 Hz. Thus two trains of responses, one beginning with a maximal response, the other with a half-maximal response, were obtained with each frequently of stimulation. Marked facilitation of the electromyographic response began with the train of stimulation, especially with tetanic stimulation. A secondary fade occurred occasionally. These changes were more remarkable in the train of half-refractory responses. We conclude that nerve stimulation facilitates neuromuscular transmission and deduce that the characteristic fade observed with a curariform block, rather than being an uncovered physiological phenomenon, is caused by tubocurarine and related drugs.", "contents": "Neuromuscular facilitation during train-of-four and tetanic stimulation in healthy volunteers: observations with half-refractory paired responses. The compound electromyographic response of the thenar musculature was elicited by supramaximal stimulation of the ulnar nerve in 12 awake healthy volunteers. The half-refractory period of the neuromuscular transmission was determined. Twin stimuli separated by the half-refractory interval were repeated as a unit at 2 Hz and at 50 Hz. Thus two trains of responses, one beginning with a maximal response, the other with a half-maximal response, were obtained with each frequently of stimulation. Marked facilitation of the electromyographic response began with the train of stimulation, especially with tetanic stimulation. A secondary fade occurred occasionally. These changes were more remarkable in the train of half-refractory responses. We conclude that nerve stimulation facilitates neuromuscular transmission and deduce that the characteristic fade observed with a curariform block, rather than being an uncovered physiological phenomenon, is caused by tubocurarine and related drugs."}
{"id": "PMID:194615", "title": "C-type and intracisternal A-type virus particles during epidermal carcinogenesis by tobacco smoke condensate in BALB/c mice.", "content": "Electron microscopic observations of sequential stages of skin carcinogenesis induced by tobacco smoke condensate (SC) and a cyclohexane fraction of tobacco smoke condensate (G) revealed an increase in incidence of intracisternal A particles within the epidermal cells. Tumours induced by SC also contained C-type particles, but these were not seen in G-induced tumours or after irritant or solvent treatment. There was no evidence of an increase in intracisternal A particles after irritant or solvent treatment. A direct relationship between the proliferation of A particles and neoplastic growth of BALB/c mouse epidermis appears likely. The data suggest possible activation of a latent C-type virus by SC.", "contents": "C-type and intracisternal A-type virus particles during epidermal carcinogenesis by tobacco smoke condensate in BALB/c mice. Electron microscopic observations of sequential stages of skin carcinogenesis induced by tobacco smoke condensate (SC) and a cyclohexane fraction of tobacco smoke condensate (G) revealed an increase in incidence of intracisternal A particles within the epidermal cells. Tumours induced by SC also contained C-type particles, but these were not seen in G-induced tumours or after irritant or solvent treatment. There was no evidence of an increase in intracisternal A particles after irritant or solvent treatment. A direct relationship between the proliferation of A particles and neoplastic growth of BALB/c mouse epidermis appears likely. The data suggest possible activation of a latent C-type virus by SC."}
{"id": "PMID:194616", "title": "Calcitonin-responsive adenylate cyclase in a calcitonin-producing human cancer cell line.", "content": "A calcitonin-responsive adenylate cyclase has been found in a cell line of a poorly differentiated bronchial carcinoma (BEN cells). The cells have previously been shown to secrete an immunoreactive form of calcitonin in culture. Salmon calcitonin (SCT), porcine calcitonin (PCT) and human calcitonin (CT-M) all stimulated adenylate cyclase activity in particulate preparations. CT-M sulphoxide had little effect. The concentrations of the calcitonins required for half the maximum activation of adenylate cyclase were 6-8, 18 and 90 nm respectively. SCT (30pm) and CT-M (60 pm) increased the intracellular concentration of cyclic AMP from 11-2+/-0-2 (s.e.) to 18-2+/-0-2 and 16-7+/-0-2 respectively over a 2-5-min period. SCT (labelled with 125I) bound to particulate preparations of Ben cells, and competition for binding occurred with unlabelled SCT and CT-M. The concentration of SCT required for half the maximum inhibition of [125I]SCT binding was 11 nm. CT-M sulphoxide inhibited only at high concentration (3 micron). The characteristics of the adenylate cyclase response to SCT did not change over the period between cell adhesion (after subculture) and confluence. However, pre-incubation of cells for 4 h with SCT (150 nm) abolished the subsequent adenylate cyclase response of particulate preparations to further hormone. The practical difficulties encountered in purifying and quantifying the large-mol.-wt. form of CT-M secreted by BEN cells has precluded direct investigation of the potential relationship between hormone secretion and the occurrence of the calcitonin receptor. This relationship is discussed in terms of its possible biological significance.", "contents": "Calcitonin-responsive adenylate cyclase in a calcitonin-producing human cancer cell line. A calcitonin-responsive adenylate cyclase has been found in a cell line of a poorly differentiated bronchial carcinoma (BEN cells). The cells have previously been shown to secrete an immunoreactive form of calcitonin in culture. Salmon calcitonin (SCT), porcine calcitonin (PCT) and human calcitonin (CT-M) all stimulated adenylate cyclase activity in particulate preparations. CT-M sulphoxide had little effect. The concentrations of the calcitonins required for half the maximum activation of adenylate cyclase were 6-8, 18 and 90 nm respectively. SCT (30pm) and CT-M (60 pm) increased the intracellular concentration of cyclic AMP from 11-2+/-0-2 (s.e.) to 18-2+/-0-2 and 16-7+/-0-2 respectively over a 2-5-min period. SCT (labelled with 125I) bound to particulate preparations of Ben cells, and competition for binding occurred with unlabelled SCT and CT-M. The concentration of SCT required for half the maximum inhibition of [125I]SCT binding was 11 nm. CT-M sulphoxide inhibited only at high concentration (3 micron). The characteristics of the adenylate cyclase response to SCT did not change over the period between cell adhesion (after subculture) and confluence. However, pre-incubation of cells for 4 h with SCT (150 nm) abolished the subsequent adenylate cyclase response of particulate preparations to further hormone. The practical difficulties encountered in purifying and quantifying the large-mol.-wt. form of CT-M secreted by BEN cells has precluded direct investigation of the potential relationship between hormone secretion and the occurrence of the calcitonin receptor. This relationship is discussed in terms of its possible biological significance."}
{"id": "PMID:194617", "title": "Properties of a cell line from human adenocarcinoma of the rectum.", "content": "A new, highly differentiated line of cells derived from adenocarcinoma of the rectum (HT55) is described. This line is noteworthy for the following features: 1. The role played in its development by the use of UV-inactivated Sendai virus to attach tumour cell clumps to plastic bottles. 2. Evidence that it produces RNA-containing material of density 1-5--1-16 g/ml. 3. Induction of bone formation in the stroma when grown in athymic mice. 4. Stimulation of primary CBA mouse embryo fibroblasts to form a transient nodule when mixed with them and injected into adult CBA mice. The karyotype and growth-cycle characteristics of the line are described.", "contents": "Properties of a cell line from human adenocarcinoma of the rectum. A new, highly differentiated line of cells derived from adenocarcinoma of the rectum (HT55) is described. This line is noteworthy for the following features: 1. The role played in its development by the use of UV-inactivated Sendai virus to attach tumour cell clumps to plastic bottles. 2. Evidence that it produces RNA-containing material of density 1-5--1-16 g/ml. 3. Induction of bone formation in the stroma when grown in athymic mice. 4. Stimulation of primary CBA mouse embryo fibroblasts to form a transient nodule when mixed with them and injected into adult CBA mice. The karyotype and growth-cycle characteristics of the line are described."}
{"id": "PMID:194618", "title": "Evaluation of 51Cr release for detecting cell-mediated cytotoxic responses to solid chemically induced rat tumours.", "content": "A 51Cr-release test was developed for the detection of cell-mediated cytotoxicity against transplanted solid chemically induced rat tumours, and the findings were compared with those obtained in parallel tests using a microcytotoxicity assay. It was necessary to incorporate several modifications of the original Brunner assay (Brunner et al., 1968) in order to increase the sensitivity of the test as applied to long-term tumour lines maintained as glass-adherent cultures. These included: 1. preincubation of labelled tumour cells at 37 degrees C for 3-4 h before addition of effector cells; 2. preincubation of effector cells at 37 degrees C for 12 h before addition to target cells; 3. upon admixture of target and effector cells, intimate cell contact was established by gentle centrifugation; 4. after incubation of target and effector cells at 37 degrees C, a further incubation for 1 h at 45 degrees C was included to complete the release of 51Cr from non-viable cells. Maximal cytotoxicity of tumour-bearer effector cells was detected after 12 h incubation of lymphoid and target cells at a ratio of 200:1. Spleen cells from tumour-bearing rats during the first 2 weeks of tumour growth exhibited the same pattern of reactivity in the 51Cr-release test and the microcytotoxicity assay, although significant reduction in target-cell numbers was more frequently recorded using the microcytotoxicity assay. Tumour-bearer spleen cells showed reactivity against the homologous tumour as well as against unrelated tumours. Using either assay, pre-exposure of effector cells to 3M KC1 extracts of tumour was found to inhibit their effect on tumour cells most frequently in tests in which the effector-cell donor, soluble extract and target cell were of the same tumour line.", "contents": "Evaluation of 51Cr release for detecting cell-mediated cytotoxic responses to solid chemically induced rat tumours. A 51Cr-release test was developed for the detection of cell-mediated cytotoxicity against transplanted solid chemically induced rat tumours, and the findings were compared with those obtained in parallel tests using a microcytotoxicity assay. It was necessary to incorporate several modifications of the original Brunner assay (Brunner et al., 1968) in order to increase the sensitivity of the test as applied to long-term tumour lines maintained as glass-adherent cultures. These included: 1. preincubation of labelled tumour cells at 37 degrees C for 3-4 h before addition of effector cells; 2. preincubation of effector cells at 37 degrees C for 12 h before addition to target cells; 3. upon admixture of target and effector cells, intimate cell contact was established by gentle centrifugation; 4. after incubation of target and effector cells at 37 degrees C, a further incubation for 1 h at 45 degrees C was included to complete the release of 51Cr from non-viable cells. Maximal cytotoxicity of tumour-bearer effector cells was detected after 12 h incubation of lymphoid and target cells at a ratio of 200:1. Spleen cells from tumour-bearing rats during the first 2 weeks of tumour growth exhibited the same pattern of reactivity in the 51Cr-release test and the microcytotoxicity assay, although significant reduction in target-cell numbers was more frequently recorded using the microcytotoxicity assay. Tumour-bearer spleen cells showed reactivity against the homologous tumour as well as against unrelated tumours. Using either assay, pre-exposure of effector cells to 3M KC1 extracts of tumour was found to inhibit their effect on tumour cells most frequently in tests in which the effector-cell donor, soluble extract and target cell were of the same tumour line."}
{"id": "PMID:194620", "title": "Abnormal platelet function in Chediak-Higashi syndrome.", "content": "Platelets in an infant with Chediak-Higashi (C-H) syndrome without bleeding manifestations and not in the accelerated phase showed abnormal function consistent with storage pool disorder as shown by abnormal aggregation, decreased storage capacity and release of [14C]5-HT, low endogenous 5-HT, reduced ATP and ADP with an increased ATP/ADP ratio, increased specific radioactivity of ADP after [14C]adenine labelling, decreased release of adenine nucleotides after stimulation, impaired secretion of acid hydrolases despite normal stores, and decreased calcium content. Incorporation of [14C]adenine into metabolic pool adenine nucleotides was normal. Nucleotide conversion to hypoxanthine in stimulated platelets was mildly impaired. Platelet cyclic-AMP (c-AMP) was initially elevated, but even when c-AMP returned to normal levels after ascorbate treatment, platelet function was not improved. Elevated intracellular c-AMP was not solely responsible for the abnormal platelet function.", "contents": "Abnormal platelet function in Chediak-Higashi syndrome. Platelets in an infant with Chediak-Higashi (C-H) syndrome without bleeding manifestations and not in the accelerated phase showed abnormal function consistent with storage pool disorder as shown by abnormal aggregation, decreased storage capacity and release of [14C]5-HT, low endogenous 5-HT, reduced ATP and ADP with an increased ATP/ADP ratio, increased specific radioactivity of ADP after [14C]adenine labelling, decreased release of adenine nucleotides after stimulation, impaired secretion of acid hydrolases despite normal stores, and decreased calcium content. Incorporation of [14C]adenine into metabolic pool adenine nucleotides was normal. Nucleotide conversion to hypoxanthine in stimulated platelets was mildly impaired. Platelet cyclic-AMP (c-AMP) was initially elevated, but even when c-AMP returned to normal levels after ascorbate treatment, platelet function was not improved. Elevated intracellular c-AMP was not solely responsible for the abnormal platelet function."}
{"id": "PMID:194621", "title": "Simultaneous presence of receptors for complement and sheep red blood cells on human fetal thymocytes.", "content": "The cells of four thymus glands, two at 12 weeks, one at 16 weeks and one at 22 weeks gestational age, were examined cytochemically for enzymic activity and for surface markers. The reactions for chloroacetate esterase, peroxidase, and alkaline phosphatase were negative and the reaction for nonspecific esterase was only weakly positive in some of the cells. In contrast, nearly all thymocytes at the 12th gestational week showed strong focal acid phosphatase (acP) activity. The number of acP-stainable cells and the staining intensity declined progressively. A high percentage of thymocytes in early fetal life express a complement receptor (CR); the proportion of CR-bearing cells decreased while cells forming rosettes with sheep erythrocytes (possessing erythrocyte receptors: ER) correspondingly increased during fetal life. Using a mixed rosette assay, up to 30% of the thymocytes at 12 weeks gestation were found to bear CR and ER simultaneously. The number of CR- and ER-positive cells also declined progressively with fetal age. These findings show that CR-positive, ER-negative thymus cells mature into CR-negative, ER-positive thymocytes via a CR-positive and ER-positive intermediate cell, indicating that mature ER-positive thymocytes do not originate from another cell line lacking CR. The changes in surface markers during early T cell maturation is relevant to certain lymphomas whose cells also show strong focal acP activity and also express both CR and ER. These lymphoma cells may correspond to fetal thymocytes or T precursor cells present in small numbers after birth.", "contents": "Simultaneous presence of receptors for complement and sheep red blood cells on human fetal thymocytes. The cells of four thymus glands, two at 12 weeks, one at 16 weeks and one at 22 weeks gestational age, were examined cytochemically for enzymic activity and for surface markers. The reactions for chloroacetate esterase, peroxidase, and alkaline phosphatase were negative and the reaction for nonspecific esterase was only weakly positive in some of the cells. In contrast, nearly all thymocytes at the 12th gestational week showed strong focal acid phosphatase (acP) activity. The number of acP-stainable cells and the staining intensity declined progressively. A high percentage of thymocytes in early fetal life express a complement receptor (CR); the proportion of CR-bearing cells decreased while cells forming rosettes with sheep erythrocytes (possessing erythrocyte receptors: ER) correspondingly increased during fetal life. Using a mixed rosette assay, up to 30% of the thymocytes at 12 weeks gestation were found to bear CR and ER simultaneously. The number of CR- and ER-positive cells also declined progressively with fetal age. These findings show that CR-positive, ER-negative thymus cells mature into CR-negative, ER-positive thymocytes via a CR-positive and ER-positive intermediate cell, indicating that mature ER-positive thymocytes do not originate from another cell line lacking CR. The changes in surface markers during early T cell maturation is relevant to certain lymphomas whose cells also show strong focal acP activity and also express both CR and ER. These lymphoma cells may correspond to fetal thymocytes or T precursor cells present in small numbers after birth."}
{"id": "PMID:194622", "title": "Effect of hyperoxia on superoxide anion and hydrogen peroxide production of polymorphonuclear leucocytes and alveolar macrophages.", "content": "Hyperoxia activates superoxide dismutase (SOD) while inactivating catalase and glutathione peroxidase in polymorphonuclear leucocytes (PMN) and alveolar marcophages (AM) obtained from guinea-pigs exposed to 85% oxygen for 90 h. The influence of these altered enzyme activities on the rate of oxygen consumption and release of superoxide anion (O--2) and hydrogen peroxide (H2O2) was investigated. By 18 h O--2 released from resting PMN increased two-fold and remained elevated through the entire periods of the study, whereas H2O2 release and oxygen consumption at the same time points remained normal. At 66 h PMN phagocytizing opsonized zymosan particles released additional quantities of O--2 and H2O2 and consumed significantly more oxygen compared to the usual increase noted at earlier time points. Although oxygen consumption was almost two-fold higher in AM than PMN, phagocytizing AM released three-fold less O--2 and five-fold less H2O2 than did PMN. Furthermore, AM of animals exposed to hyperoxia no longer exhibited enhanced O--2 production upon exposure to opsonized zymosan. Hydrogen peroxide release progressively decreased at rest but progressively increased during phagocytosis of opsonized zymosan during the 90 h exposure to hyperoxia. No changes in oxygen consumption of AM occurred during hyperoxia. The divergent oxidative responses in PMN and AM of guinea-pigs exposed to hyperoxia suggest different biochemical adaptive mechanisms.", "contents": "Effect of hyperoxia on superoxide anion and hydrogen peroxide production of polymorphonuclear leucocytes and alveolar macrophages. Hyperoxia activates superoxide dismutase (SOD) while inactivating catalase and glutathione peroxidase in polymorphonuclear leucocytes (PMN) and alveolar marcophages (AM) obtained from guinea-pigs exposed to 85% oxygen for 90 h. The influence of these altered enzyme activities on the rate of oxygen consumption and release of superoxide anion (O--2) and hydrogen peroxide (H2O2) was investigated. By 18 h O--2 released from resting PMN increased two-fold and remained elevated through the entire periods of the study, whereas H2O2 release and oxygen consumption at the same time points remained normal. At 66 h PMN phagocytizing opsonized zymosan particles released additional quantities of O--2 and H2O2 and consumed significantly more oxygen compared to the usual increase noted at earlier time points. Although oxygen consumption was almost two-fold higher in AM than PMN, phagocytizing AM released three-fold less O--2 and five-fold less H2O2 than did PMN. Furthermore, AM of animals exposed to hyperoxia no longer exhibited enhanced O--2 production upon exposure to opsonized zymosan. Hydrogen peroxide release progressively decreased at rest but progressively increased during phagocytosis of opsonized zymosan during the 90 h exposure to hyperoxia. No changes in oxygen consumption of AM occurred during hyperoxia. The divergent oxidative responses in PMN and AM of guinea-pigs exposed to hyperoxia suggest different biochemical adaptive mechanisms."}
{"id": "PMID:194623", "title": "[Phospholipid composition of nuclear membranes and cell nuclei of rat liver and hepatoma 27].", "content": "Phospholipid composition of nuclei and nuclear membranes from rat liver and hepatoma-27 were investigated. Hepatoma nuclei and nuclear membranes were found to contain cardiolipin which was absent in the same fractions of rat liver. In the nuclei and nuclear membranes of hepatoma the content of sphingomyelin was higher and that of lecithin is lower than in the corresponding subcellular fractions of  rat liver. The content of acid phospholipids was much higher in hepatoma nuclear membranes than those of the normal liver. The data obtained show that the general trend of lipid dedifferentiation which earlier was demonstrated for various membranes of different tumor cells is observed also in the case of nuclear membranes.", "contents": "[Phospholipid composition of nuclear membranes and cell nuclei of rat liver and hepatoma 27]. Phospholipid composition of nuclei and nuclear membranes from rat liver and hepatoma-27 were investigated. Hepatoma nuclei and nuclear membranes were found to contain cardiolipin which was absent in the same fractions of rat liver. In the nuclei and nuclear membranes of hepatoma the content of sphingomyelin was higher and that of lecithin is lower than in the corresponding subcellular fractions of  rat liver. The content of acid phospholipids was much higher in hepatoma nuclear membranes than those of the normal liver. The data obtained show that the general trend of lipid dedifferentiation which earlier was demonstrated for various membranes of different tumor cells is observed also in the case of nuclear membranes."}
{"id": "PMID:194624", "title": "[Use of specific angiotensin inhibitors in the study of hormone-receptor interaction].", "content": "The specificity of receptors participating in the interaction with angiotensin II (AT 1--8) fragments, e. g. N-terminal tri-(AT 1--3), C-terminal penta-(AT 4--8), and middle tetrapeptide (at 3--6), was studied in experiments on rat ascending colon which were performed to investigate the influence of a specific angiotensin antagonist, /1-hydantoic acid, 5-valine, 8-alanine/-angiotensin (HAAT 1--8), on myotropic effects of these fragments as well as the influence of the fragments on the myotropic activity of the whole hormone molecule. Competitive antagonism was found between HAAT 1--8 and AT 4--8 and AT 3--6 and between these fragments and AT 1--8. No antagonisma was revealed between AT 1--3 and HAAT 1--8, and between AT 1--3 and AT 1--8. It is assumed that the fragments AT 4--8 and AT 3--6 interact at the level of angiotensin receptors, and that of AT 1--3 at the level of non-specific receptors. A new model for the structural and functional organization of angiotensin is proposed.", "contents": "[Use of specific angiotensin inhibitors in the study of hormone-receptor interaction]. The specificity of receptors participating in the interaction with angiotensin II (AT 1--8) fragments, e. g. N-terminal tri-(AT 1--3), C-terminal penta-(AT 4--8), and middle tetrapeptide (at 3--6), was studied in experiments on rat ascending colon which were performed to investigate the influence of a specific angiotensin antagonist, /1-hydantoic acid, 5-valine, 8-alanine/-angiotensin (HAAT 1--8), on myotropic effects of these fragments as well as the influence of the fragments on the myotropic activity of the whole hormone molecule. Competitive antagonism was found between HAAT 1--8 and AT 4--8 and AT 3--6 and between these fragments and AT 1--8. No antagonisma was revealed between AT 1--3 and HAAT 1--8, and between AT 1--3 and AT 1--8. It is assumed that the fragments AT 4--8 and AT 3--6 interact at the level of angiotensin receptors, and that of AT 1--3 at the level of non-specific receptors. A new model for the structural and functional organization of angiotensin is proposed."}
{"id": "PMID:194625", "title": "[Electrogenic function of submitochondrial particles at the water-octane interphases].", "content": "Studies on submitochondrial particles (SMP) preparation showed that in the sourse of the redox reactions at the octane-water interface, catalyzed by SMP enzymes, the charges are transferred from the aqueous to the octane phase. The effects were detected by a shift of the Volta potential, using the vibrating electrode method. In the presence of 2-N-methyl-amino-1,4-naphthoquinone in octane, acting as electron acceptor, the negative charges were transferred from water to octane following the oxidation of NADH, succinate and ascorbate. The charging of the octane phase was sensitive to the inhibitors of the respiratory chain, e. g. rotenone, antimycin and cyanide. In the presence of 2,4-DNP in octane, acting as a proton acceptor, the oxidation of NADH and succinate by ferricyanide, catalyzed by CMP in the presence of antimycin and cyanide correspondingly, was followed by a transfer of positive charges from water to octane. The positive charging of the octane phase, coupled with NADH oxidation, was found insensitive to rotenone, and that coupled with succinate oxidation, was completely inhibited by antimycin. The positive charging of the octane phase was also observed during the reverse transhydrogenase reaction, catalyzed by SMP at the division of the phases. The effect was inhibited by palmitoyl-CoA.", "contents": "[Electrogenic function of submitochondrial particles at the water-octane interphases]. Studies on submitochondrial particles (SMP) preparation showed that in the sourse of the redox reactions at the octane-water interface, catalyzed by SMP enzymes, the charges are transferred from the aqueous to the octane phase. The effects were detected by a shift of the Volta potential, using the vibrating electrode method. In the presence of 2-N-methyl-amino-1,4-naphthoquinone in octane, acting as electron acceptor, the negative charges were transferred from water to octane following the oxidation of NADH, succinate and ascorbate. The charging of the octane phase was sensitive to the inhibitors of the respiratory chain, e. g. rotenone, antimycin and cyanide. In the presence of 2,4-DNP in octane, acting as a proton acceptor, the oxidation of NADH and succinate by ferricyanide, catalyzed by CMP in the presence of antimycin and cyanide correspondingly, was followed by a transfer of positive charges from water to octane. The positive charging of the octane phase, coupled with NADH oxidation, was found insensitive to rotenone, and that coupled with succinate oxidation, was completely inhibited by antimycin. The positive charging of the octane phase was also observed during the reverse transhydrogenase reaction, catalyzed by SMP at the division of the phases. The effect was inhibited by palmitoyl-CoA."}
{"id": "PMID:194626", "title": "[Detection of multiple forms of polyphosphate phosphohydrolase from Endomyces magnusii].", "content": "Labile polyphosphate phosphohydrolase from Endomyces magnusii is 27-fold purified by means of fractionation with ammonium sulphate, gel filtration on Sephadex G-75 and Biogel P-60 and chromatography on DEAE cellulose. Chromatography on DEAE Sephadex A-50, isoelelctric focusing and polyacrylamide gel electrophoresis of the enzyme preparation revealed 3 different fractions with polyphosphate phosphohydrolase activity (PPPH1, PPPH2 and PPPH3). Relative content of these fractions in E. magnusii cells is 30%, 55% and 15% respectively. Isoelectric points are: PPPH1--pH 5.1--5.2; PPPH2--pH 6.0--6.1; PPPH3--pH 6.3--6.4. PPPH1 and PPPH2 are found to be the most labile. PPPH3 is more stable under isolation procedure and storage. The fractions have similar molecular weight (48 000 +/- 3000).", "contents": "[Detection of multiple forms of polyphosphate phosphohydrolase from Endomyces magnusii]. Labile polyphosphate phosphohydrolase from Endomyces magnusii is 27-fold purified by means of fractionation with ammonium sulphate, gel filtration on Sephadex G-75 and Biogel P-60 and chromatography on DEAE cellulose. Chromatography on DEAE Sephadex A-50, isoelelctric focusing and polyacrylamide gel electrophoresis of the enzyme preparation revealed 3 different fractions with polyphosphate phosphohydrolase activity (PPPH1, PPPH2 and PPPH3). Relative content of these fractions in E. magnusii cells is 30%, 55% and 15% respectively. Isoelectric points are: PPPH1--pH 5.1--5.2; PPPH2--pH 6.0--6.1; PPPH3--pH 6.3--6.4. PPPH1 and PPPH2 are found to be the most labile. PPPH3 is more stable under isolation procedure and storage. The fractions have similar molecular weight (48 000 +/- 3000)."}
{"id": "PMID:194627", "title": "[Sulfhydryl groups of cyclic AMP-dependent histone kinase from pig brain].", "content": "A preparative method of isolation of the histone kinase regulatory subunit has been developed. The total number of cysteine residues in the enzyme (13 residues) and in each of its subunits (3 residues in the catalytic subunit and 10 residues in the regulatory one), has been determined. Two disulfide bridges have been found in the regulatory subunits. The relative availability of the sulfhydryl groups with respect to different modifying agents has been studied. It has been demonstrated that SH-groups blocking does not change essentially the enzyme activity.", "contents": "[Sulfhydryl groups of cyclic AMP-dependent histone kinase from pig brain]. A preparative method of isolation of the histone kinase regulatory subunit has been developed. The total number of cysteine residues in the enzyme (13 residues) and in each of its subunits (3 residues in the catalytic subunit and 10 residues in the regulatory one), has been determined. Two disulfide bridges have been found in the regulatory subunits. The relative availability of the sulfhydryl groups with respect to different modifying agents has been studied. It has been demonstrated that SH-groups blocking does not change essentially the enzyme activity."}
{"id": "PMID:194628", "title": "[Structural-functional changes in the synaptic membranes of the cerebral cortex of rats during electric stimulation in vitro].", "content": "Electric stimulation (EC) of a suspension of native synaptic membranes of rat brain cortex in the Krebs-Ringer-glucose medium revealed Ca-dependent inhibition of Na+, K+-ATPase and inhibition of transport Ca-activated, Mg-dependent ATPase. The effects observed are not induced by a change in the SH-groups of the membrane proteins and are removed by an addition of total lipids of the brain (membrane protein: lipid = 5:1) or 0.35 mM novocaine. Cyclic 3',5'-AMP in concentrations of 0.1--1.0 mM causes an inhibition (up to 50%) of Na+, K+-ATPase of native synaptic membranes. The Na+, K+-ATPase activity of purified membrane preparations is not changed either by the cyclic nucleotide, or by EC. It is assumed that depolarization of excitable membranes results in structural changes, mediated by the activation of protein kinase, and manifesting themselves as labilization of protein-lipid ratios.", "contents": "[Structural-functional changes in the synaptic membranes of the cerebral cortex of rats during electric stimulation in vitro]. Electric stimulation (EC) of a suspension of native synaptic membranes of rat brain cortex in the Krebs-Ringer-glucose medium revealed Ca-dependent inhibition of Na+, K+-ATPase and inhibition of transport Ca-activated, Mg-dependent ATPase. The effects observed are not induced by a change in the SH-groups of the membrane proteins and are removed by an addition of total lipids of the brain (membrane protein: lipid = 5:1) or 0.35 mM novocaine. Cyclic 3',5'-AMP in concentrations of 0.1--1.0 mM causes an inhibition (up to 50%) of Na+, K+-ATPase of native synaptic membranes. The Na+, K+-ATPase activity of purified membrane preparations is not changed either by the cyclic nucleotide, or by EC. It is assumed that depolarization of excitable membranes results in structural changes, mediated by the activation of protein kinase, and manifesting themselves as labilization of protein-lipid ratios."}
{"id": "PMID:194629", "title": "[Various enzymes of isolated nuclear membranes and cell nuclei of the liver and hepatoma 27 of rats].", "content": "A comparative study of glucose-6-phosphatase, alcaline RNase, ATPase, inosine diphosphatase and 5'-nucleotidase activities in isolated rat liver and hepatoma-27 nuclei and nuclear envelopes was performed. The tumor nuclear membranes were shown to be free from G-6-Pase activity in contrast to the liver nuclear membranes. The nuclear RNase activity was strongly inhibited in the hepatoma and could be unmasked in the presence of 3-10(-4) M pCMB. Hepatoma nuclear and nuclear envelopes ATP-ase activity was found to be moderately decreased as compared to those of the normal tissue. The values of inosine diphosphatase activity in hepatoma were similar to those in liver. The role of the nuclear envelope in nuclear-cytoplasmic interactions as well as nuclear location of G-6-Pase are discussed.", "contents": "[Various enzymes of isolated nuclear membranes and cell nuclei of the liver and hepatoma 27 of rats]. A comparative study of glucose-6-phosphatase, alcaline RNase, ATPase, inosine diphosphatase and 5'-nucleotidase activities in isolated rat liver and hepatoma-27 nuclei and nuclear envelopes was performed. The tumor nuclear membranes were shown to be free from G-6-Pase activity in contrast to the liver nuclear membranes. The nuclear RNase activity was strongly inhibited in the hepatoma and could be unmasked in the presence of 3-10(-4) M pCMB. Hepatoma nuclear and nuclear envelopes ATP-ase activity was found to be moderately decreased as compared to those of the normal tissue. The values of inosine diphosphatase activity in hepatoma were similar to those in liver. The role of the nuclear envelope in nuclear-cytoplasmic interactions as well as nuclear location of G-6-Pase are discussed."}
{"id": "PMID:194632", "title": "Possible mechanisms involved in the stereotyped behavior elicited by amphetamine.", "content": "In a variety of animals, amphetamine administration produces an increase in locomotor behavior and an induction of repetitive, stereotyped behaviors. There is now considerable evidence to suggest that the induction of stereotyped behaviors is accomplished, in part, by alterations in catecholaminergic transmission in the central nervous system. By recording the spontaneous activity of neurons in the rat brain substantia nigra, reticular formation, basal ganglia, and elsewhere during systemic administration of amphetamine and related drugs, or during administration by means of microinfusions directly into these brain regions, relationships may be drawn between the biochemical and behavioral effects of these drugs and drug-induced changes in neuronal activity in the central nerovous system. Current evidence, for example, suggests that amphetamine produces an inhibition of neuronal activity in the neostriatum and pars compacta of the substantia nigra by means of dopamine released from dopaminergic terminals in the neostriatum and dopaminergic dendrites in the substantia nigra respectively. In addition, current evidence suggests the possibility of a GABA-mediated functional antagonism between excitatory cortical and/or thalamic input to the neostriatum and dopaminergic input from the substantia nigra which could be involved in the apparently mutually exclusive occurrence of amphetamine-induced locomotion and stereotyped behaviors that follow amphetamine administration. Such evidence may also have relevance to a variety of behavioral disorders involving the basal ganglia and catecholaminergic transmission in the central nervous system.", "contents": "Possible mechanisms involved in the stereotyped behavior elicited by amphetamine. In a variety of animals, amphetamine administration produces an increase in locomotor behavior and an induction of repetitive, stereotyped behaviors. There is now considerable evidence to suggest that the induction of stereotyped behaviors is accomplished, in part, by alterations in catecholaminergic transmission in the central nervous system. By recording the spontaneous activity of neurons in the rat brain substantia nigra, reticular formation, basal ganglia, and elsewhere during systemic administration of amphetamine and related drugs, or during administration by means of microinfusions directly into these brain regions, relationships may be drawn between the biochemical and behavioral effects of these drugs and drug-induced changes in neuronal activity in the central nerovous system. Current evidence, for example, suggests that amphetamine produces an inhibition of neuronal activity in the neostriatum and pars compacta of the substantia nigra by means of dopamine released from dopaminergic terminals in the neostriatum and dopaminergic dendrites in the substantia nigra respectively. In addition, current evidence suggests the possibility of a GABA-mediated functional antagonism between excitatory cortical and/or thalamic input to the neostriatum and dopaminergic input from the substantia nigra which could be involved in the apparently mutually exclusive occurrence of amphetamine-induced locomotion and stereotyped behaviors that follow amphetamine administration. Such evidence may also have relevance to a variety of behavioral disorders involving the basal ganglia and catecholaminergic transmission in the central nervous system."}
{"id": "PMID:194633", "title": "The pathophysiologic basis of tardive dyskinesia.", "content": "The prolonged course of tardive dyskinesia (TD) associated with antipsychotic drugs suggests that permanent structural alterations of the brain occur, though neurohistopathological studies have provided little to support this view. An alternative view is that functional adaptive changes may account for the manifestations of TD. A currently popular hypothesis is that there may be a functional excess in the activity of dopamine (DA) as a synaptic neurotransmitter in the basal ganglia. A cholinergic mechanism has also been implicated in TD, but the clinical effects of acetylcholine agonists and antagonists in TD are variable. In animals, nigrostriatal neurons respond to the blockade of DA synapses by treatment with antipsychotic agents in several ways, including acute and transient increases in the turnover of DA, and more slowly evolving \"disuse\" supersensitivity, possibly of postsynaptic receptors. The latter effects have been studied extensively in animal models of presumably DA-mediated behavior, by chemical studies of DA-sensitive adenylate cyclase in caudate nucleus in vitro, and by studies of labeled dopamine receptors. The phenomenon of DA-supersensitivity might help to explain some of the acute \"withdrawal dyskinesias\" that follow the abrupt discontinuation of high doses of antipsychotic agents, and might contribute to other reversible forms of the syndrome, but may be too short-lived to explain the persistent forms of TD. It must be concluded that an explanation of the latter syndrome of persistent drug-related TD remains uncertain.", "contents": "The pathophysiologic basis of tardive dyskinesia. The prolonged course of tardive dyskinesia (TD) associated with antipsychotic drugs suggests that permanent structural alterations of the brain occur, though neurohistopathological studies have provided little to support this view. An alternative view is that functional adaptive changes may account for the manifestations of TD. A currently popular hypothesis is that there may be a functional excess in the activity of dopamine (DA) as a synaptic neurotransmitter in the basal ganglia. A cholinergic mechanism has also been implicated in TD, but the clinical effects of acetylcholine agonists and antagonists in TD are variable. In animals, nigrostriatal neurons respond to the blockade of DA synapses by treatment with antipsychotic agents in several ways, including acute and transient increases in the turnover of DA, and more slowly evolving \"disuse\" supersensitivity, possibly of postsynaptic receptors. The latter effects have been studied extensively in animal models of presumably DA-mediated behavior, by chemical studies of DA-sensitive adenylate cyclase in caudate nucleus in vitro, and by studies of labeled dopamine receptors. The phenomenon of DA-supersensitivity might help to explain some of the acute \"withdrawal dyskinesias\" that follow the abrupt discontinuation of high doses of antipsychotic agents, and might contribute to other reversible forms of the syndrome, but may be too short-lived to explain the persistent forms of TD. It must be concluded that an explanation of the latter syndrome of persistent drug-related TD remains uncertain."}
{"id": "PMID:194635", "title": "Human cytomegalovirus: a review of developments between 1970 and 1976. Part II. Experimental developments.", "content": "Over the last 6 years, our knowledge of the basic characteristics of human cytomegalovirus (HCMV) has been greatly enhanced, especially as concerns the microbiology of this virus. DNA relatedness studies show that there is 80% homology between different strains, regardless of their origin. Studies on the relationships between HCMV and host-cell metabolism reveal that it  induces both a virus specific and a cellular DNA polymerase, stimulates ribosomal RNA, induces early protein synthesis and results in the liberation of \"intrinsic\" interferon. The sequence of appearance of virus-specific antigens, as well as the presence of virus-induced IgG-Fc receptors has been described. New morphological aspects of the virus itself, as well as of the lesions which it provokes, have been observed. Last, but perhaps most important, evidence is accumulating in favor of the oncogenic potential of this virus. These basic aspects of HCMV are presented and discussed herein, along with the effects of various drugs and supra-optimal temperature on the virus and the possibility of preparing a vaccine against it.", "contents": "Human cytomegalovirus: a review of developments between 1970 and 1976. Part II. Experimental developments. Over the last 6 years, our knowledge of the basic characteristics of human cytomegalovirus (HCMV) has been greatly enhanced, especially as concerns the microbiology of this virus. DNA relatedness studies show that there is 80% homology between different strains, regardless of their origin. Studies on the relationships between HCMV and host-cell metabolism reveal that it  induces both a virus specific and a cellular DNA polymerase, stimulates ribosomal RNA, induces early protein synthesis and results in the liberation of \"intrinsic\" interferon. The sequence of appearance of virus-specific antigens, as well as the presence of virus-induced IgG-Fc receptors has been described. New morphological aspects of the virus itself, as well as of the lesions which it provokes, have been observed. Last, but perhaps most important, evidence is accumulating in favor of the oncogenic potential of this virus. These basic aspects of HCMV are presented and discussed herein, along with the effects of various drugs and supra-optimal temperature on the virus and the possibility of preparing a vaccine against it."}
{"id": "PMID:194636", "title": "Health of the intensively treated hemophiliac, with special reference to abnormal liver chemistries and splenomegaly.", "content": "Liver function abnormalities have been noted in intensively treated hemophiliacs, and have led to less aggressive application of pooled plasma products by some physicians. In a prospective study, liver function was abnormal in 68 of 98 hemophiliacs. The abnormalities of hepatic function tended to persist over a 1-yr study period. There was no correlation between these abnormalities and the age of the patient, the presence of hepatitis-associated antigen or antibody, the presence or absence of splenomegaly (which was found in 26 of 98 patients), the number of infusions of plasma products, the type of hemophilia, or the type of product infused. Titers of antibodies to cytomegalovirus were generally higher in hemophilic patients than in a control group of healthy volunteers. These abnormalities did not suggest that a less aggressive infusion regimen was indicated for the hemophiliac, but did suggest the need for careful long-term observation of such patients.", "contents": "Health of the intensively treated hemophiliac, with special reference to abnormal liver chemistries and splenomegaly. Liver function abnormalities have been noted in intensively treated hemophiliacs, and have led to less aggressive application of pooled plasma products by some physicians. In a prospective study, liver function was abnormal in 68 of 98 hemophiliacs. The abnormalities of hepatic function tended to persist over a 1-yr study period. There was no correlation between these abnormalities and the age of the patient, the presence of hepatitis-associated antigen or antibody, the presence or absence of splenomegaly (which was found in 26 of 98 patients), the number of infusions of plasma products, the type of hemophilia, or the type of product infused. Titers of antibodies to cytomegalovirus were generally higher in hemophilic patients than in a control group of healthy volunteers. These abnormalities did not suggest that a less aggressive infusion regimen was indicated for the hemophiliac, but did suggest the need for careful long-term observation of such patients."}
{"id": "PMID:194639", "title": "Intracellular enzymes of collagen biosynthesis in human platelets.", "content": "Activities of four intracellular enzymes of collagen biosynthesis--prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase, and collagen glucosyltransferase--were demonstrated in human platelets, and the presence of prolyl hydroxylase protein was further demonstrated by direct radioimmunoassay. The ratio of the specific activities of the four enzymes in the four enzymes in the human platelet extract to those in human adult skin extract varied from about 0.1 to 1, the lowest relative activity being found with prolyl hydroxylase and the highest with collagen glucosyltransferase. Only a very small amount of prolyl hydroxylase protein, probably 1%, was in the form of the active enzyme tetramer. The collagen glucosyltransferase from human platelets readily glucosylated galactosylhydroxylysine in denatured collagen, but did not glucosylate native collagen. Also, native collagen did not act as an inhibitor of the glucosylation reaction. Therefore, platelet collagen glucosyltransferase cannot form either an enzyme--substrate complex or an enzyme--inhibitor complex with native collagen. The results thus argue against the theory which maintains that platelet collagen glucosyltransferase is involved in collagen--platelet adhesion.", "contents": "Intracellular enzymes of collagen biosynthesis in human platelets. Activities of four intracellular enzymes of collagen biosynthesis--prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase, and collagen glucosyltransferase--were demonstrated in human platelets, and the presence of prolyl hydroxylase protein was further demonstrated by direct radioimmunoassay. The ratio of the specific activities of the four enzymes in the four enzymes in the human platelet extract to those in human adult skin extract varied from about 0.1 to 1, the lowest relative activity being found with prolyl hydroxylase and the highest with collagen glucosyltransferase. Only a very small amount of prolyl hydroxylase protein, probably 1%, was in the form of the active enzyme tetramer. The collagen glucosyltransferase from human platelets readily glucosylated galactosylhydroxylysine in denatured collagen, but did not glucosylate native collagen. Also, native collagen did not act as an inhibitor of the glucosylation reaction. Therefore, platelet collagen glucosyltransferase cannot form either an enzyme--substrate complex or an enzyme--inhibitor complex with native collagen. The results thus argue against the theory which maintains that platelet collagen glucosyltransferase is involved in collagen--platelet adhesion."}
{"id": "PMID:194640", "title": "Parallel tubular arrays in severe combined immunodeficiency disease: an ultrastructural study of peripheral blood lymphocytes.", "content": "The ultrastructure of the lymphocytes from three children with severe combined immunodeficiency disease (SCID) is described. Parallel tubular arrays (PTA) were found in a large percentage of circulating lymphocytes (53%, 41%, and 13%) in three SCID patients when compared to age-matched controls. The size of these inclusions was quite variable, with some attaining a length of 1.7 micrometer. They contained a tubular substructure with a diameter of 36--44 nm. The PTA were mostly located in the centriolar and Golgi regions of the cytoplasm, and were sometimes membrane bound. A centriolar origin of the inclusion was suggested. A second inclusion, the tubuloreticular structure, was found in only 1.4% of the circulating lymphocytes from one SCID patient. The origin of the PTA and its occurrence in severe combined immunodeficiency disease are discussed.", "contents": "Parallel tubular arrays in severe combined immunodeficiency disease: an ultrastructural study of peripheral blood lymphocytes. The ultrastructure of the lymphocytes from three children with severe combined immunodeficiency disease (SCID) is described. Parallel tubular arrays (PTA) were found in a large percentage of circulating lymphocytes (53%, 41%, and 13%) in three SCID patients when compared to age-matched controls. The size of these inclusions was quite variable, with some attaining a length of 1.7 micrometer. They contained a tubular substructure with a diameter of 36--44 nm. The PTA were mostly located in the centriolar and Golgi regions of the cytoplasm, and were sometimes membrane bound. A centriolar origin of the inclusion was suggested. A second inclusion, the tubuloreticular structure, was found in only 1.4% of the circulating lymphocytes from one SCID patient. The origin of the PTA and its occurrence in severe combined immunodeficiency disease are discussed."}
{"id": "PMID:194641", "title": "Myeloperoxidase--H2O2--halide system: cytotoxic effect on human blood leukocytes.", "content": "Myeloperoxidase, H2O2, and a halide form a potent antimicrobial and cytotoxic system of the polymorphonuclear leukocyte. A cytotoxic effect of this system on human blood leukocytes is demonstrated, employing 51Cr release and dye exclusion assays. Cytotoxicity is dependent on enzymatically active myeloperoxidase, H2O2, or a peroxide-generating enzyme system and either chloride or iodide. Cell damage is rapid, with maximal levels of 51Cr release occurring within 30--60 min. Approximately equal sensitivity to the peroxidase system is observed for polymorphonuclear leukocytes and mononuclear leukocytes. Since myeloperoxidase and H2O2 are released from polymorphonuclear leukocytes under certain conditions, such as during particle ingestion, it is suggested that peroxidase-mediated leukocyte injury may be an important feature of the inflammatory response.", "contents": "Myeloperoxidase--H2O2--halide system: cytotoxic effect on human blood leukocytes. Myeloperoxidase, H2O2, and a halide form a potent antimicrobial and cytotoxic system of the polymorphonuclear leukocyte. A cytotoxic effect of this system on human blood leukocytes is demonstrated, employing 51Cr release and dye exclusion assays. Cytotoxicity is dependent on enzymatically active myeloperoxidase, H2O2, or a peroxide-generating enzyme system and either chloride or iodide. Cell damage is rapid, with maximal levels of 51Cr release occurring within 30--60 min. Approximately equal sensitivity to the peroxidase system is observed for polymorphonuclear leukocytes and mononuclear leukocytes. Since myeloperoxidase and H2O2 are released from polymorphonuclear leukocytes under certain conditions, such as during particle ingestion, it is suggested that peroxidase-mediated leukocyte injury may be an important feature of the inflammatory response."}
{"id": "PMID:194642", "title": "Metabolic activity of phagocytosing granulocytes in chronic granulocytic leukemia: ultrastructural observation of a degranulation defect.", "content": "The functional capacities of granulocytes in patients with chronic granulocytic leukemia are still a subject of controversy, probably due to the heterogeneity of the abnormalities observed from patient to patient. For a better definition of these abnormalities, 14 patients with untreated chronic granulocytic leukemia were studied. The patients were divided into three groups on the basis of the functional activities of their phagocytosing granulocytes. In four patients (group I), the granulocytes were normal in respect to particle ingestion, nitroblue tetrazolium (NBT)-stimulated reduction, cyanide-insensitive oxygen (O2) consumption, superoxide anion (O2-)-stimulated production, hydrogen peroxide (H2O2) production, and iodination. They also had a normal myeloperoxidase (MPO) content. In four patients (group III), the granulocytes were significantly defective in all of these activities. In the six remaining patients (group II), all the initial metabolic steps of the phagocytosing granulocytes (ingestion, NBT reduction, O2 consumption, O2-production, H2O2 production) were normal, as were the MPO content of the granulocytes, while iodination was strikingly decreased. These metabolic features suggested a degranulation defect which was observed ultrastructurally in the only patient studied among these six. The phagocytosing granulocytes of this patient did not degranulate and no deposits of MPO activity were seen in the phagosomes.", "contents": "Metabolic activity of phagocytosing granulocytes in chronic granulocytic leukemia: ultrastructural observation of a degranulation defect. The functional capacities of granulocytes in patients with chronic granulocytic leukemia are still a subject of controversy, probably due to the heterogeneity of the abnormalities observed from patient to patient. For a better definition of these abnormalities, 14 patients with untreated chronic granulocytic leukemia were studied. The patients were divided into three groups on the basis of the functional activities of their phagocytosing granulocytes. In four patients (group I), the granulocytes were normal in respect to particle ingestion, nitroblue tetrazolium (NBT)-stimulated reduction, cyanide-insensitive oxygen (O2) consumption, superoxide anion (O2-)-stimulated production, hydrogen peroxide (H2O2) production, and iodination. They also had a normal myeloperoxidase (MPO) content. In four patients (group III), the granulocytes were significantly defective in all of these activities. In the six remaining patients (group II), all the initial metabolic steps of the phagocytosing granulocytes (ingestion, NBT reduction, O2 consumption, O2-production, H2O2 production) were normal, as were the MPO content of the granulocytes, while iodination was strikingly decreased. These metabolic features suggested a degranulation defect which was observed ultrastructurally in the only patient studied among these six. The phagocytosing granulocytes of this patient did not degranulate and no deposits of MPO activity were seen in the phagosomes."}
{"id": "PMID:194643", "title": "Cold agglutinins in infectious mononucleosis and heterophil-antibody-negative mononucleosis-like syndromes.", "content": "Cold agglutinins (CA) were evaluated prospectively in patients with various mononucleosis syndromes and in a large control group. Cold agglutinins with anti-i specificity were seen mainly in heterophil-positive or -negative Epstein-Barr virus (EBV)-induced infectious mononucleosis (31.8% of cases). Unclassified CA with equal reactivity against cord and adult erythrocytes were seen in 56 of 150 (37.3%) cases of heterophil-antibody-positive infectious mononucleosis (IM), in 1 of 7 (14.3%) cases of heterophil-negative EBV-induced IM, and in 12 of 31 (38.7%) cases of the heterophil-negative mononucleosis-like syndrome due to cytomegalovirus or other unspecified agents. One patient with heterophil-positive IM had a persistent, partially papain sensitive CA with anti-Pr-like activity. Anti-i CA were seen in less than 1.0% of healthy young adults (500) or patients without mononucleosis (500) submitted for heterophil studies. Unclassified CA were noted in 3.2% of the latter 1000 samples.", "contents": "Cold agglutinins in infectious mononucleosis and heterophil-antibody-negative mononucleosis-like syndromes. Cold agglutinins (CA) were evaluated prospectively in patients with various mononucleosis syndromes and in a large control group. Cold agglutinins with anti-i specificity were seen mainly in heterophil-positive or -negative Epstein-Barr virus (EBV)-induced infectious mononucleosis (31.8% of cases). Unclassified CA with equal reactivity against cord and adult erythrocytes were seen in 56 of 150 (37.3%) cases of heterophil-antibody-positive infectious mononucleosis (IM), in 1 of 7 (14.3%) cases of heterophil-negative EBV-induced IM, and in 12 of 31 (38.7%) cases of the heterophil-negative mononucleosis-like syndrome due to cytomegalovirus or other unspecified agents. One patient with heterophil-positive IM had a persistent, partially papain sensitive CA with anti-Pr-like activity. Anti-i CA were seen in less than 1.0% of healthy young adults (500) or patients without mononucleosis (500) submitted for heterophil studies. Unclassified CA were noted in 3.2% of the latter 1000 samples."}
{"id": "PMID:194644", "title": "Induction of human granulocyte differentiation in vitro by ubiquitin and thymopoietin.", "content": "Human bone marrow cells were separated according to density by centrifugation on Ficoll-Hypaque gradients and then according to size by velocity sedimentation. This procedure resulted in fractions enriched for immature granulocytes, mature granulocytes, and lymphocytes. Cells in these fractions were analyzed for their expression of certain surface and functional differentiation markers and for their ability to respond to thymopoietin and ubiquitin with the expression of additional differentiation markers. A higher percentage of band form and segmented granulocytes than of more immature granulocytes expressed complement receptors on their surfaces. Thymopoietin and ubiquitin induced a significant percentage of the cells in the immature granulocyte fraction to express this marker. These data suggested that the complement receptor may be viewed as a differentiation marker on human granulocytes, the expression of which can be induced in vitro by thymopoietin and ubiquitin. Furthermore, fractions containing predominantly band form granulocytes were induced by ubiquitin (but not thymopoietin) to develop the capacity to respond to chemotactic agents, and cell fractions containing predominantly myelocytes and metamyelocytes were induced by thymopoietin and ubiquitin to develop the capacity to phagocytose latex particles. These findings indicated that thymopoietin and ubiquitin, two agents known to induce a number of stages of human and mouse lymphocyte differentiation, are also capable of inducing some stages of human granulocyte differentiation in vitro.", "contents": "Induction of human granulocyte differentiation in vitro by ubiquitin and thymopoietin. Human bone marrow cells were separated according to density by centrifugation on Ficoll-Hypaque gradients and then according to size by velocity sedimentation. This procedure resulted in fractions enriched for immature granulocytes, mature granulocytes, and lymphocytes. Cells in these fractions were analyzed for their expression of certain surface and functional differentiation markers and for their ability to respond to thymopoietin and ubiquitin with the expression of additional differentiation markers. A higher percentage of band form and segmented granulocytes than of more immature granulocytes expressed complement receptors on their surfaces. Thymopoietin and ubiquitin induced a significant percentage of the cells in the immature granulocyte fraction to express this marker. These data suggested that the complement receptor may be viewed as a differentiation marker on human granulocytes, the expression of which can be induced in vitro by thymopoietin and ubiquitin. Furthermore, fractions containing predominantly band form granulocytes were induced by ubiquitin (but not thymopoietin) to develop the capacity to respond to chemotactic agents, and cell fractions containing predominantly myelocytes and metamyelocytes were induced by thymopoietin and ubiquitin to develop the capacity to phagocytose latex particles. These findings indicated that thymopoietin and ubiquitin, two agents known to induce a number of stages of human and mouse lymphocyte differentiation, are also capable of inducing some stages of human granulocyte differentiation in vitro."}
{"id": "PMID:194648", "title": "Memory performance after arousal from different sleep stages.", "content": "Learning material was presented to independent groups of subjects either after arousal from non-Rapid Eye Movement (non-REM) sleep, after arousal from REM sleep, or under conditions of no prior sleep. Measures of immediate and subsequent free recall were taken. Memory performance was found to be impaired where learning took place after non-REM arousal. This was manifest in the number of categories recalled, over both immediate and subsequent recall, and in the number of items recalled per category over subsequent recall. It was suggested that the memory performance decrement after non-REM arousal may be understood in terms of a retrieval deficit as well as a coding deficit. It is possible that the former is consequent upon a lower general level of arousal, whereas the latter is specific to memory.", "contents": "Memory performance after arousal from different sleep stages. Learning material was presented to independent groups of subjects either after arousal from non-Rapid Eye Movement (non-REM) sleep, after arousal from REM sleep, or under conditions of no prior sleep. Measures of immediate and subsequent free recall were taken. Memory performance was found to be impaired where learning took place after non-REM arousal. This was manifest in the number of categories recalled, over both immediate and subsequent recall, and in the number of items recalled per category over subsequent recall. It was suggested that the memory performance decrement after non-REM arousal may be understood in terms of a retrieval deficit as well as a coding deficit. It is possible that the former is consequent upon a lower general level of arousal, whereas the latter is specific to memory."}
{"id": "PMID:194650", "title": "Evolution of poliovirus since introduction of attenuated vaccine.", "content": "Genetic marker tests were performed on 997 strains of poliovirus isolated from patients with neurological disease and from healthy people in England and Wales. Before the introduction of live attenuated vaccine most strains could multiply at raised temperatures. Now, however, many strains isolated from cases of poliomyelitis or from healthy persons with no known contact with vaccine cannot grow above 37 degrees C, and in this respect resemble the vaccine strains. The three serotypes are also much more evenly represented. Hence probably to a limited extent the vaccine-like strains have established themselves in the community.", "contents": "Evolution of poliovirus since introduction of attenuated vaccine. Genetic marker tests were performed on 997 strains of poliovirus isolated from patients with neurological disease and from healthy people in England and Wales. Before the introduction of live attenuated vaccine most strains could multiply at raised temperatures. Now, however, many strains isolated from cases of poliomyelitis or from healthy persons with no known contact with vaccine cannot grow above 37 degrees C, and in this respect resemble the vaccine strains. The three serotypes are also much more evenly represented. Hence probably to a limited extent the vaccine-like strains have established themselves in the community."}
{"id": "PMID:194654", "title": "Estradiol and testosterone binding in normal and mutant mouse cerebellum: biochemical and cellular specificity.", "content": "Estradiol and testosterone binding macromolecules are demonstrated in normal mouse cerebellum. Identity of the estradiol binder as the 'receptor' is provided by its binding to DNA-cellulose, which does not occur for other estradiol binding proteins. The androgen binder is identified as 'receptor' by its specific deficiency (85% reduced) in the androgen-insensitive mutant mouse, testicular feminization (Tfm). The relative amounts of these two components are reversed in cerebellum compared to hypothalamus-preoptic area. Neurological mouse mutants, which lack specified neurons, are examined to test for the cells in which these hormone binding proteins are located. Experiments with Purkinje cell degeneration (pcd), weaver (wv) and staggerer (sg), suggest that the majority of these receptors are present in granule cells.", "contents": "Estradiol and testosterone binding in normal and mutant mouse cerebellum: biochemical and cellular specificity. Estradiol and testosterone binding macromolecules are demonstrated in normal mouse cerebellum. Identity of the estradiol binder as the 'receptor' is provided by its binding to DNA-cellulose, which does not occur for other estradiol binding proteins. The androgen binder is identified as 'receptor' by its specific deficiency (85% reduced) in the androgen-insensitive mutant mouse, testicular feminization (Tfm). The relative amounts of these two components are reversed in cerebellum compared to hypothalamus-preoptic area. Neurological mouse mutants, which lack specified neurons, are examined to test for the cells in which these hormone binding proteins are located. Experiments with Purkinje cell degeneration (pcd), weaver (wv) and staggerer (sg), suggest that the majority of these receptors are present in granule cells."}
{"id": "PMID:194655", "title": "Prostaglandin E2, cyclic adenosine monophosphate and morphine analgesia.", "content": "Intravenous administration of prostaglandin E2 (PGE2) to mice results in a significant distribution of PGE2 into the brain and an elevation of cyclic adenosine monophosphate (cAMP) in the midhindbrain and corpus striatum. Neither acute morphine administration nor morphine tolerance alters this response. Morphine alone also elevates cAMP levels. Although these elevations are blocked by the narcotic antagonist, naloxone, they only occur at supra-analgesic doses. Therefore morphine analgesia does not correlate with either elevation of cAMP levels of antagonism of PGE2-induced elevations of cAMP.", "contents": "Prostaglandin E2, cyclic adenosine monophosphate and morphine analgesia. Intravenous administration of prostaglandin E2 (PGE2) to mice results in a significant distribution of PGE2 into the brain and an elevation of cyclic adenosine monophosphate (cAMP) in the midhindbrain and corpus striatum. Neither acute morphine administration nor morphine tolerance alters this response. Morphine alone also elevates cAMP levels. Although these elevations are blocked by the narcotic antagonist, naloxone, they only occur at supra-analgesic doses. Therefore morphine analgesia does not correlate with either elevation of cAMP levels of antagonism of PGE2-induced elevations of cAMP."}
{"id": "PMID:194656", "title": "Purkinje cell activity during motor learning.", "content": "Monkeys were trained to grasp a handle and move it in a horizontal arc to a central position by flexing or extending the wrist. A torque motor applied forces to the handle that switched at random intervals to alternately load flexor and extensor muscles. At each load switch, the handle was displaced transiently from the central position, and then moved back by the monkeys and held there steadily again. Recordings were made from cerebellar Purkinje cells (P-cells) whose simple spike (SS) activity was related to the task. The magnitude of one of the oppositely directed loads was then altered and the monkeys took about 12-100 trials with the novel load before performing as regularly as previously. During this period with one known and one novel load, some P-cells underwent increases in complex spike (CS) frequency at specific times after the load switch. This increased CS frequency would last for a similar number of trials as that taken by the monkey to adapt to the novel load before decreasing to near its previous level. Associated with the increased CS frequency ther were decreases in SS frequency that persisted after the CS frequency had decreased to near its previous level. These results are consistent with theoretical proposals that motor learning takes place in the cerebellum through changes in the strength of transmission of parallel fiber synapses on P-cells caused by the climbing fiber input. These results further suggest that climbing fiber firing causes a decrease in the strength of parallel fiber synapses.", "contents": "Purkinje cell activity during motor learning. Monkeys were trained to grasp a handle and move it in a horizontal arc to a central position by flexing or extending the wrist. A torque motor applied forces to the handle that switched at random intervals to alternately load flexor and extensor muscles. At each load switch, the handle was displaced transiently from the central position, and then moved back by the monkeys and held there steadily again. Recordings were made from cerebellar Purkinje cells (P-cells) whose simple spike (SS) activity was related to the task. The magnitude of one of the oppositely directed loads was then altered and the monkeys took about 12-100 trials with the novel load before performing as regularly as previously. During this period with one known and one novel load, some P-cells underwent increases in complex spike (CS) frequency at specific times after the load switch. This increased CS frequency would last for a similar number of trials as that taken by the monkey to adapt to the novel load before decreasing to near its previous level. Associated with the increased CS frequency ther were decreases in SS frequency that persisted after the CS frequency had decreased to near its previous level. These results are consistent with theoretical proposals that motor learning takes place in the cerebellum through changes in the strength of transmission of parallel fiber synapses on P-cells caused by the climbing fiber input. These results further suggest that climbing fiber firing causes a decrease in the strength of parallel fiber synapses."}
{"id": "PMID:194658", "title": "Autoradiographic localization of opiate receptors in rat brain. II. The brain stem.", "content": "The distribution of opiate receptors, determined by the autoradiographic localization of stereospecific [3H]diprenorphine binding sites, was studied in the brain stem. Areas showing very dense or dense localizations of receptors included the parabrachial nuclei, the superior colliculus, the ventral median raphe nucleus, components of the accessory optic system, portions of the habenulo-interpeduncular complex, the pretectal nuclei and the ventral lateral geniculate, the infundibulum and the medial thalamus. Moderate grain densities were found in broad areas of the upper medulla, midbrain and diencephalon. The significance of these findings are discussed in terms of pain mechanisms, association of some receptors with small diameter axons, pupillary reflexes, hormonal control, and effects of opiates on neurotransmitter systems.", "contents": "Autoradiographic localization of opiate receptors in rat brain. II. The brain stem. The distribution of opiate receptors, determined by the autoradiographic localization of stereospecific [3H]diprenorphine binding sites, was studied in the brain stem. Areas showing very dense or dense localizations of receptors included the parabrachial nuclei, the superior colliculus, the ventral median raphe nucleus, components of the accessory optic system, portions of the habenulo-interpeduncular complex, the pretectal nuclei and the ventral lateral geniculate, the infundibulum and the medial thalamus. Moderate grain densities were found in broad areas of the upper medulla, midbrain and diencephalon. The significance of these findings are discussed in terms of pain mechanisms, association of some receptors with small diameter axons, pupillary reflexes, hormonal control, and effects of opiates on neurotransmitter systems."}
{"id": "PMID:194661", "title": "Effect of clofibrate treatment on chronic hyperlipidemia induced by an ACTH-producing tumor.", "content": "Plasma triglyceride and cholesterol levels were significantly increased in rats bearing an MtT-F4 tumor for 31-41 days. Addition of clofibrate at a dose of 30 mg kg-1 to the diet of rats bearing the tumor resulted in the complete elimination of the tumor effect on the plasma triglycerides, and to a great extent prevented the rise in the plasma cholesterol.", "contents": "Effect of clofibrate treatment on chronic hyperlipidemia induced by an ACTH-producing tumor. Plasma triglyceride and cholesterol levels were significantly increased in rats bearing an MtT-F4 tumor for 31-41 days. Addition of clofibrate at a dose of 30 mg kg-1 to the diet of rats bearing the tumor resulted in the complete elimination of the tumor effect on the plasma triglycerides, and to a great extent prevented the rise in the plasma cholesterol."}
{"id": "PMID:194662", "title": "Cyclic AMP and the positive inotropic effect of norepinephrine and phenylephrine.", "content": "Time-response studies of the effects of norepinephrine and phenylephrine revealed that both agonists caused an increase in cyclic AMP levels before increases in contractile force in either the electrically stimulated left atria or spontaneously beating right atria of the rat. Norepinephrine caused a nearly sixfold increase in cyclic AMP, whereas phenylephrine produced only a 50% increase in the nucleotide. Pretreatment with reserpine did not affect the norepinephrine cyclic AMP response; however, the phenylephrine cyclic AMP response was abolished. Reserpine pretreatment did not significantly affect the contractile responses of either amine. In the presence of propranolol, norepinephrine was found to have the ability to produce an increace in contractile force in which cyclic AMP was apparently not involved. The time course of the contractile response induced by adrenergic amines was found to be remarkably influenced by the chronotropic response in spontaneously beating preparations while the cyclic AMP response was not greatly affected. This difference in the contractile response may be due to the ability of the chronotropic response to influence the flux of calcium through the cell membrane.", "contents": "Cyclic AMP and the positive inotropic effect of norepinephrine and phenylephrine. Time-response studies of the effects of norepinephrine and phenylephrine revealed that both agonists caused an increase in cyclic AMP levels before increases in contractile force in either the electrically stimulated left atria or spontaneously beating right atria of the rat. Norepinephrine caused a nearly sixfold increase in cyclic AMP, whereas phenylephrine produced only a 50% increase in the nucleotide. Pretreatment with reserpine did not affect the norepinephrine cyclic AMP response; however, the phenylephrine cyclic AMP response was abolished. Reserpine pretreatment did not significantly affect the contractile responses of either amine. In the presence of propranolol, norepinephrine was found to have the ability to produce an increace in contractile force in which cyclic AMP was apparently not involved. The time course of the contractile response induced by adrenergic amines was found to be remarkably influenced by the chronotropic response in spontaneously beating preparations while the cyclic AMP response was not greatly affected. This difference in the contractile response may be due to the ability of the chronotropic response to influence the flux of calcium through the cell membrane."}
{"id": "PMID:194663", "title": "Pyocin sensitivity of pseudomonas aeruginosa pretreated with antibiotics.", "content": "Strains of Pseudomonas aeruginosa exposed to subinhibitory concentrations of either polymyxin B, gentamicin, or carbenicillin were compared with untreated organisms for changes in sensitivity to pyocin. Pretreatment with polymyxin B or gentamicin resulted in a decreased sensitivity to pyocin, while carbenicllin pretreatment did not alter pyocin sensitivity.", "contents": "Pyocin sensitivity of pseudomonas aeruginosa pretreated with antibiotics. Strains of Pseudomonas aeruginosa exposed to subinhibitory concentrations of either polymyxin B, gentamicin, or carbenicillin were compared with untreated organisms for changes in sensitivity to pyocin. Pretreatment with polymyxin B or gentamicin resulted in a decreased sensitivity to pyocin, while carbenicllin pretreatment did not alter pyocin sensitivity."}
{"id": "PMID:194664", "title": "The structure of cellulose-producing bacteria, Acetobacter xylinum and Acetobacter acetigenus.", "content": "The structure of the pellicles and cells of the cellulose-producing bacteria, Acetobacter xylinum and Acetobacter acetigenus, was studied by transmission electron microscopy of thin sections and freeze-etch replicas of glucose-stimulated cell suspensions, quiescent cell suspensions, and discrete pellicles. These bacteria have a relatively thin cell wall in section, with several irregular features superimposed on an otherwise simple, Gram-negative morphology. There are no flagella or pili. Unfixed, unextracted cells, viewed as whole mounts, show spherical or ellipsoidal bodies of undetermined composition which disappear after extraction with water or ethanol and propylene oxide. For both species, there are several kinds of cell surface irregularities, some of which are localized protrusions of the cell envelope. A variety of irregularities is seen frequently on cells in the first minutes of glucose incubation, on cells in a discrete pellicle, on quiescent cells, and on starved cells. Immediately after the addition of glucose to cellulose-free cells in suspension culture, fine fibrils appear on and (or) near the cell envelope. The fine fibrils are frequently as small as 3 nm in diameter in both freeze-etch and thin-section preparations and are frequently associated with freshly synthesized cellulose fibrils. Starved cells in suspensions free of (classical) microfibrils sometimes reveal stubs of an extracellular structure whose morphology resembles that of a nascent cellulose fibril.", "contents": "The structure of cellulose-producing bacteria, Acetobacter xylinum and Acetobacter acetigenus. The structure of the pellicles and cells of the cellulose-producing bacteria, Acetobacter xylinum and Acetobacter acetigenus, was studied by transmission electron microscopy of thin sections and freeze-etch replicas of glucose-stimulated cell suspensions, quiescent cell suspensions, and discrete pellicles. These bacteria have a relatively thin cell wall in section, with several irregular features superimposed on an otherwise simple, Gram-negative morphology. There are no flagella or pili. Unfixed, unextracted cells, viewed as whole mounts, show spherical or ellipsoidal bodies of undetermined composition which disappear after extraction with water or ethanol and propylene oxide. For both species, there are several kinds of cell surface irregularities, some of which are localized protrusions of the cell envelope. A variety of irregularities is seen frequently on cells in the first minutes of glucose incubation, on cells in a discrete pellicle, on quiescent cells, and on starved cells. Immediately after the addition of glucose to cellulose-free cells in suspension culture, fine fibrils appear on and (or) near the cell envelope. The fine fibrils are frequently as small as 3 nm in diameter in both freeze-etch and thin-section preparations and are frequently associated with freshly synthesized cellulose fibrils. Starved cells in suspensions free of (classical) microfibrils sometimes reveal stubs of an extracellular structure whose morphology resembles that of a nascent cellulose fibril."}
{"id": "PMID:194665", "title": "Carcinoembryonic antigen in cancer of the female reproductive system. Serial plasma values correlated with disease state.", "content": "The results of plasma carcinoembryonic antigen (CEA) determinations done over 600 patients with gynecologic malignancy will be presented. It would appear from this extensive survey that the likelihood of a patient having a positive value is increased with advancing stage and bulk of disease. The incidence of positive values in patients with clinical recurrence is quite impressive and presents a possible mode of follow-up for patients after standard treatment techniques have been administered for cervical cancer. Most interesting is the effect of radiation therapy or surgery on squamous cell cancer of the cervix and vulva in patients who have a positive value of the onset. Treatment of the disease by either modality appears to be associated with a precipitous drop in plasma value of CEA. Unfortunately, the presence or absence of CEA is not reliable and to date it is impossible to predict which patients with gynecologic malignancy will manifest a positive plasma value. Comments will be made concerning retro-de-differentiation and de-repression as a mechanism for the production of this antigen in patients with gynecologic cancer.", "contents": "Carcinoembryonic antigen in cancer of the female reproductive system. Serial plasma values correlated with disease state. The results of plasma carcinoembryonic antigen (CEA) determinations done over 600 patients with gynecologic malignancy will be presented. It would appear from this extensive survey that the likelihood of a patient having a positive value is increased with advancing stage and bulk of disease. The incidence of positive values in patients with clinical recurrence is quite impressive and presents a possible mode of follow-up for patients after standard treatment techniques have been administered for cervical cancer. Most interesting is the effect of radiation therapy or surgery on squamous cell cancer of the cervix and vulva in patients who have a positive value of the onset. Treatment of the disease by either modality appears to be associated with a precipitous drop in plasma value of CEA. Unfortunately, the presence or absence of CEA is not reliable and to date it is impossible to predict which patients with gynecologic malignancy will manifest a positive plasma value. Comments will be made concerning retro-de-differentiation and de-repression as a mechanism for the production of this antigen in patients with gynecologic cancer."}
{"id": "PMID:194666", "title": "Membranous basal cell adenoma of parotid gland, dermal cylindromas, and trichoepitheliomas. Comparative histochemistry and ultrastructure.", "content": "A basal cell adenoma of parotid, eccrine dermal cylindromas and trichoepitheliomas occurring in the same patient were examined by light and electron microscopy and histochemistry. The eccrine and parotid adenomas were similar both structurally and histochemically except for the presence of Langerhans cells in the cutaneous adenoma and well differentiated mucinous cells in the parotid tumor. The three different hamartomas found in this individual may represent the effect of a single pleiotropic gene acting on ontogenetically related stem cells.", "contents": "Membranous basal cell adenoma of parotid gland, dermal cylindromas, and trichoepitheliomas. Comparative histochemistry and ultrastructure. A basal cell adenoma of parotid, eccrine dermal cylindromas and trichoepitheliomas occurring in the same patient were examined by light and electron microscopy and histochemistry. The eccrine and parotid adenomas were similar both structurally and histochemically except for the presence of Langerhans cells in the cutaneous adenoma and well differentiated mucinous cells in the parotid tumor. The three different hamartomas found in this individual may represent the effect of a single pleiotropic gene acting on ontogenetically related stem cells."}
{"id": "PMID:194667", "title": "Extramammary Paget's disease of the vulva. A clinicopathologic study of 13 cases.", "content": "The clinicopathologic findings of 13 patients having extramammary Paget's disease of the vulva are discussed with emphasis on its histogenesis and biological behavior. For the purpose of study and assessment of prognosis, these cases were divided into two groups, those with an underlying invasive cutaneous adnexal adenocarcinoma, and those lacking an underlying invasive lesion. Four cases contained invasive cutaneous adnexal adenocarcinoma; in one of these the invasion was superficial. Three of the cases with an invasive lesion and three other cases showed in situ adenocarcinoma of sweat glands. Surgical treatment is mandatory for both groups of patients. The prognosis was excellent for the patients having Paget's disease without an underlying invasive carcinoma. From the literature, the prognosis of those with an underlying invasive carcinoma of the vulva appears to be less favorable. Multiple surgical excisions may be required to control the recurrences and metastases. A frequent association with other internal malignancy was observed. In four cases, second malignancies were found. Of special interest was the demonstration in one case of columns of neoplastic cells extending from involved sweat glands to the surface epithelium via the intradermal sweat duct. Our study leads us to support the concept that the Paget's cells, in a number of cases, are derived from an underlying carcinoma in situ of sweat gland origin.", "contents": "Extramammary Paget's disease of the vulva. A clinicopathologic study of 13 cases. The clinicopathologic findings of 13 patients having extramammary Paget's disease of the vulva are discussed with emphasis on its histogenesis and biological behavior. For the purpose of study and assessment of prognosis, these cases were divided into two groups, those with an underlying invasive cutaneous adnexal adenocarcinoma, and those lacking an underlying invasive lesion. Four cases contained invasive cutaneous adnexal adenocarcinoma; in one of these the invasion was superficial. Three of the cases with an invasive lesion and three other cases showed in situ adenocarcinoma of sweat glands. Surgical treatment is mandatory for both groups of patients. The prognosis was excellent for the patients having Paget's disease without an underlying invasive carcinoma. From the literature, the prognosis of those with an underlying invasive carcinoma of the vulva appears to be less favorable. Multiple surgical excisions may be required to control the recurrences and metastases. A frequent association with other internal malignancy was observed. In four cases, second malignancies were found. Of special interest was the demonstration in one case of columns of neoplastic cells extending from involved sweat glands to the surface epithelium via the intradermal sweat duct. Our study leads us to support the concept that the Paget's cells, in a number of cases, are derived from an underlying carcinoma in situ of sweat gland origin."}
{"id": "PMID:194668", "title": "The relationship between nephroblastoma and neurofibromatosis (Von Recklinghausen's disease).", "content": "Three cases with co-existent Wilm's tumor and Von Recklinghausen's Disease from a series of 342 nephroblastomas are discussed as to the significance of this association. Biological arguments favor a positive link because of the multiplicity of associative lesions which parallel each other, the co-existence of which suggests a common genetic bond. An embryologic association is described whereby early mutational events, i.e. neural induction of nephrogenesis, may link these two entities in utero. Further interconnection is stated statistically, in that nephroblastoma patients in this series had a 29 fold higher incidence of multiple neurofibromatosis than predicted for in the general population. The co-existent diseases in the three cases observed are approximately 33-50% more than can be accounted for by chance in the United States population. Malignant transformation in neurofibromatosis is discussed because of the therapeutic implications presented by two of the three Wilms' tumor patients studied.", "contents": "The relationship between nephroblastoma and neurofibromatosis (Von Recklinghausen's disease). Three cases with co-existent Wilm's tumor and Von Recklinghausen's Disease from a series of 342 nephroblastomas are discussed as to the significance of this association. Biological arguments favor a positive link because of the multiplicity of associative lesions which parallel each other, the co-existence of which suggests a common genetic bond. An embryologic association is described whereby early mutational events, i.e. neural induction of nephrogenesis, may link these two entities in utero. Further interconnection is stated statistically, in that nephroblastoma patients in this series had a 29 fold higher incidence of multiple neurofibromatosis than predicted for in the general population. The co-existent diseases in the three cases observed are approximately 33-50% more than can be accounted for by chance in the United States population. Malignant transformation in neurofibromatosis is discussed because of the therapeutic implications presented by two of the three Wilms' tumor patients studied."}
{"id": "PMID:194669", "title": "Mucinous (adenocystic) carcinoma of sweat glands with widespread metastasis. Case report with ultrastructural study.", "content": "An unusual case of mucinous adenocarcinoma of the sweat glands originating from the right axilla is described. Despite complete control of the primary tumor after local excision, diffuse metastatic lesions continued to appear in the scalp, face, upper and lower extremities, sacral and pelvic bones, and left posterior iliac bone marrow space. The tumors were radioresistant. Multiple trials of various chemotherapeutic regimens, including alkylating agents, antifolates, antipyrimidines, vinca alkaloids, and antineoplastic antibiotics, were ineffective. The cutaneous neoplasms were grossly round, smooth, red, glistening, and cystic and were filled with a gelatinous mucinous material. Microscopic and ultrastructural findings are described.", "contents": "Mucinous (adenocystic) carcinoma of sweat glands with widespread metastasis. Case report with ultrastructural study. An unusual case of mucinous adenocarcinoma of the sweat glands originating from the right axilla is described. Despite complete control of the primary tumor after local excision, diffuse metastatic lesions continued to appear in the scalp, face, upper and lower extremities, sacral and pelvic bones, and left posterior iliac bone marrow space. The tumors were radioresistant. Multiple trials of various chemotherapeutic regimens, including alkylating agents, antifolates, antipyrimidines, vinca alkaloids, and antineoplastic antibiotics, were ineffective. The cutaneous neoplasms were grossly round, smooth, red, glistening, and cystic and were filled with a gelatinous mucinous material. Microscopic and ultrastructural findings are described."}
{"id": "PMID:194670", "title": "Bone-marrow examination in the staging of small-cell anaplastic carcinoma of the lung with special reference to subtyping. An evaluation of 203 consecutive patients.", "content": "Histologic examination of bone-marrow from the posterior iliac crest was routinely done as a pretreatment staging procedure in 203 consecutive patients with small-cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 27.8% with \"fusiform\" cell type (WHO II,1), 28.3% with \"polygonal\" cell type (WHO II,2), 42.8% with \"lymphocyte-like\" cell type (WHO II,3), and 1.1% with mixed types (WHO II,4). Bone-marrow involvement was found in 17.2%. No significant difference was observed among the histological subtypes with regard to bone-marrow involvement. A comparison of bone-marrow biopsy and aspiration in patients investigated with both procedures showed that aspiration alone was diagnostic in nine of 24 (38%) positive patients as compared with two of 24 (8%) with biopsy alone, while in the remaining 13 patients (54%) both procedures were positive. Of the 35 patients with positive bone-marrow examination, 77% had no other evidence of distant metastatic disease if liver metastases identified by peritoneoscopy and liver biopsy are excluded as a staging procedure. With the exception of thrombocytopenia which was observed in six patients, with bone-marrow metastases, hematological findings were of little value in detecting bone-marrow involvement.", "contents": "Bone-marrow examination in the staging of small-cell anaplastic carcinoma of the lung with special reference to subtyping. An evaluation of 203 consecutive patients. Histologic examination of bone-marrow from the posterior iliac crest was routinely done as a pretreatment staging procedure in 203 consecutive patients with small-cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 27.8% with \"fusiform\" cell type (WHO II,1), 28.3% with \"polygonal\" cell type (WHO II,2), 42.8% with \"lymphocyte-like\" cell type (WHO II,3), and 1.1% with mixed types (WHO II,4). Bone-marrow involvement was found in 17.2%. No significant difference was observed among the histological subtypes with regard to bone-marrow involvement. A comparison of bone-marrow biopsy and aspiration in patients investigated with both procedures showed that aspiration alone was diagnostic in nine of 24 (38%) positive patients as compared with two of 24 (8%) with biopsy alone, while in the remaining 13 patients (54%) both procedures were positive. Of the 35 patients with positive bone-marrow examination, 77% had no other evidence of distant metastatic disease if liver metastases identified by peritoneoscopy and liver biopsy are excluded as a staging procedure. With the exception of thrombocytopenia which was observed in six patients, with bone-marrow metastases, hematological findings were of little value in detecting bone-marrow involvement."}
{"id": "PMID:194671", "title": "Lung cancer type in relation to cigarette dosage.", "content": "In a retrospective study of 1,228 white males with histologically confirmed bronchogenic carcinoma, the proportion of squamous cell carcinoma increased with increasing age at diagnosis. Since the distribution of cell types was much the same in the 73% of cases aged 50-69, the relationship of cancer type to daily cigarette dosage was studied in this group. Squamous cell carcinoma increased from 48% of those men who smoked less than 20 cigarettes per day to 61% of those who smoked 40 or more cigarettes per day. Comparison with other studies showed conflicting results.", "contents": "Lung cancer type in relation to cigarette dosage. In a retrospective study of 1,228 white males with histologically confirmed bronchogenic carcinoma, the proportion of squamous cell carcinoma increased with increasing age at diagnosis. Since the distribution of cell types was much the same in the 73% of cases aged 50-69, the relationship of cancer type to daily cigarette dosage was studied in this group. Squamous cell carcinoma increased from 48% of those men who smoked less than 20 cigarettes per day to 61% of those who smoked 40 or more cigarettes per day. Comparison with other studies showed conflicting results."}
{"id": "PMID:194672", "title": "Congenital hepatic fibrosis, liver cell carcinoma and adult polycystic kidneys.", "content": "In reviewing the literature, we found no liver cell carcinoma (LCC) or well-documented adult polycystic kidneys (APK) associated with congenital hepatic fibrosis (CHF). We report a 69-year-old man with CHF, LCC, APK, duplication cyst of distal portion of stomach, two calcified splenic artery aneurysms, myocardial fibrosis and muscular hypertrophy of esophagus. The LCC was grossly predunculated and microscopically showed prominent fibrosis and hyaline intracytoplasmic inclusions in the tumor cells.", "contents": "Congenital hepatic fibrosis, liver cell carcinoma and adult polycystic kidneys. In reviewing the literature, we found no liver cell carcinoma (LCC) or well-documented adult polycystic kidneys (APK) associated with congenital hepatic fibrosis (CHF). We report a 69-year-old man with CHF, LCC, APK, duplication cyst of distal portion of stomach, two calcified splenic artery aneurysms, myocardial fibrosis and muscular hypertrophy of esophagus. The LCC was grossly predunculated and microscopically showed prominent fibrosis and hyaline intracytoplasmic inclusions in the tumor cells."}
{"id": "PMID:194673", "title": "Double primary cancers in 2 young sibs, leukemia in another, and dextrocardia in a fourth.", "content": "Two brothers developed multiple primary neoplasms in childhood; one had glioblastoma and non-Hodgkin's lymphoma at age 11 years, and the other brain tumor and acute leukemia at six years. A third brother died with myelogenous leukemia at thre years, and a fourth with cyanotic congenital heart disease at 11 weeks. Each child also had at least one hamartomatous lesion of the skin. The clinical features suggested von Recklinghausen's neurofibromatosis or other inherited cancer syndrome, but laboratory studies identified no markers of susceptibility to familial neoplasia.", "contents": "Double primary cancers in 2 young sibs, leukemia in another, and dextrocardia in a fourth. Two brothers developed multiple primary neoplasms in childhood; one had glioblastoma and non-Hodgkin's lymphoma at age 11 years, and the other brain tumor and acute leukemia at six years. A third brother died with myelogenous leukemia at thre years, and a fourth with cyanotic congenital heart disease at 11 weeks. Each child also had at least one hamartomatous lesion of the skin. The clinical features suggested von Recklinghausen's neurofibromatosis or other inherited cancer syndrome, but laboratory studies identified no markers of susceptibility to familial neoplasia."}
{"id": "PMID:194674", "title": "Hepatoblastoma in infant sister and brother.", "content": "Two infants, a sister with motor retardation and brother with slight microcephaly and an undescended testis, died of hepatoblastoma. Only another documented familial occurrence of this tumor, affecting siblings of the same sex, can be found in the literature. The two patients described in this paper exhibited high platelet counts prior to liver resection. Although iron deficiency may have contributed to the thrombocytosis, the finding of many megakariocytes within the hepatoblastomas suggests an intra-tumoral production of platelets. An epidemiological investigation of the family under study failed to yield conclusive data. Hepatoblastoma is a rare tumor, but it may affect more than one sibling. Therefore, periodic clinical and laboratory evaluations of the siblings at risk appear to be justified.", "contents": "Hepatoblastoma in infant sister and brother. Two infants, a sister with motor retardation and brother with slight microcephaly and an undescended testis, died of hepatoblastoma. Only another documented familial occurrence of this tumor, affecting siblings of the same sex, can be found in the literature. The two patients described in this paper exhibited high platelet counts prior to liver resection. Although iron deficiency may have contributed to the thrombocytosis, the finding of many megakariocytes within the hepatoblastomas suggests an intra-tumoral production of platelets. An epidemiological investigation of the family under study failed to yield conclusive data. Hepatoblastoma is a rare tumor, but it may affect more than one sibling. Therefore, periodic clinical and laboratory evaluations of the siblings at risk appear to be justified."}
{"id": "PMID:194675", "title": "Differences in mouse mammary tumor viruses. Relationship to early and late occurring mammary tumors.", "content": "The murine model has been used extensively to study the various factors involved in the etiology of mammary carcinoma. Inbred mouse strains have been classically categorized into (i) high incidence stains with tumors occurring relatively early in the life of the animal, or (ii) low or moderate incidence strains with tumors occurring later on in life. We have radioactively labeled the RNA genome of the mouse mammary tumor virus (MMTV) from each of several mouse strains. We report here, using the technique of molecular hybridization, that the class of MMTVs responsible for the early occurring mammary tumors in high incidence strains can be clearly distinguished from the MMTVs associated with late occurring mammary tumors in low or moderate incidence strains; we also demonstrate that minor differences in MMTV genomes can also exist within these classes. Our findings show that MMTVs are transmitted via the germ line (as a germinal provirus) in some mouse strains, whereas in other strains, a non-germ line transmission is clearly demonstrated. Biochemical techniques can thus be used to track the mode of transmission of oncogenic viruses. The relationship of these findings to an understanding of the etiology of mammary carcinoma is discussed.", "contents": "Differences in mouse mammary tumor viruses. Relationship to early and late occurring mammary tumors. The murine model has been used extensively to study the various factors involved in the etiology of mammary carcinoma. Inbred mouse strains have been classically categorized into (i) high incidence stains with tumors occurring relatively early in the life of the animal, or (ii) low or moderate incidence strains with tumors occurring later on in life. We have radioactively labeled the RNA genome of the mouse mammary tumor virus (MMTV) from each of several mouse strains. We report here, using the technique of molecular hybridization, that the class of MMTVs responsible for the early occurring mammary tumors in high incidence strains can be clearly distinguished from the MMTVs associated with late occurring mammary tumors in low or moderate incidence strains; we also demonstrate that minor differences in MMTV genomes can also exist within these classes. Our findings show that MMTVs are transmitted via the germ line (as a germinal provirus) in some mouse strains, whereas in other strains, a non-germ line transmission is clearly demonstrated. Biochemical techniques can thus be used to track the mode of transmission of oncogenic viruses. The relationship of these findings to an understanding of the etiology of mammary carcinoma is discussed."}
{"id": "PMID:194676", "title": "Biology of breast preneoplasia.", "content": "The literature dealing with mammary cancer and the presence of the identifiable preneoplastic lesions in the mammary gland of several species has been reviewed. A discrete morphologically identifiable lesion with a high malignant potential is considered preneoplastic. Lobuloalveolar lesions have been identified in the human mammary gland which fit most of the criteria for preneoplasia. The lesions, hyperplastic atypical lobules, are multicentric, have a high statistical association with breast cancer and demonstrate a morphological progression through dysplasia to frank carcinoma. Other breast lesions have a high statistical association but no morphological progression can be seen and their neoplastic potential remains unknown. The significance of these correlations is enhanced by the occurrence of homologous breast lesions in outbred and inbred animal models. Statistical correlation with breast cancer and aberrant morphology has been accepted as presumptive evidence of preneoplasia in some animals. Definitive proof of the  neoplastic potential has been obtained in rodent models by transplantation of the suspected lesions and their subsequent development into cancers. Although a strong morphological and statistical analogy exists between the human and animal models, the causes and biological potential of the human lesions await experimental proof.", "contents": "Biology of breast preneoplasia. The literature dealing with mammary cancer and the presence of the identifiable preneoplastic lesions in the mammary gland of several species has been reviewed. A discrete morphologically identifiable lesion with a high malignant potential is considered preneoplastic. Lobuloalveolar lesions have been identified in the human mammary gland which fit most of the criteria for preneoplasia. The lesions, hyperplastic atypical lobules, are multicentric, have a high statistical association with breast cancer and demonstrate a morphological progression through dysplasia to frank carcinoma. Other breast lesions have a high statistical association but no morphological progression can be seen and their neoplastic potential remains unknown. The significance of these correlations is enhanced by the occurrence of homologous breast lesions in outbred and inbred animal models. Statistical correlation with breast cancer and aberrant morphology has been accepted as presumptive evidence of preneoplasia in some animals. Definitive proof of the  neoplastic potential has been obtained in rodent models by transplantation of the suspected lesions and their subsequent development into cancers. Although a strong morphological and statistical analogy exists between the human and animal models, the causes and biological potential of the human lesions await experimental proof."}
{"id": "PMID:194678", "title": "The concept of minimal breast cancer and the pathologist's role in the diagnosis of \"early carcinoma\".", "content": "Minimal breast cancer has been variously defined as a lesion 1 cm or less, or even 5 mm or less. Some authorities consider intraductal cancer and lobular carcinoma in situ as minimal, but we believe that these should be excluded from consideration. Minimal cancer is not early cancer inasmuch as a 1 cm lesion represents 30 doubling times, and a certain percentage of these small cancers have already disseminated. The pathologist's responsibility in diagnosing minimal cancer has become more difficult. His problem is in three major areas: Is this proliferative cystic lesion cancer? Is this lobular or intraductal proliferative lesion in situ carcinoma? And if so, he must be concerned also with the treatment as well as the diagnosis. In any screening program, these minimal cancers, either invasive or in situ, should be evaluated by a group of experts in order that the program be entirely accurate.", "contents": "The concept of minimal breast cancer and the pathologist's role in the diagnosis of \"early carcinoma\". Minimal breast cancer has been variously defined as a lesion 1 cm or less, or even 5 mm or less. Some authorities consider intraductal cancer and lobular carcinoma in situ as minimal, but we believe that these should be excluded from consideration. Minimal cancer is not early cancer inasmuch as a 1 cm lesion represents 30 doubling times, and a certain percentage of these small cancers have already disseminated. The pathologist's responsibility in diagnosing minimal cancer has become more difficult. His problem is in three major areas: Is this proliferative cystic lesion cancer? Is this lobular or intraductal proliferative lesion in situ carcinoma? And if so, he must be concerned also with the treatment as well as the diagnosis. In any screening program, these minimal cancers, either invasive or in situ, should be evaluated by a group of experts in order that the program be entirely accurate."}
{"id": "PMID:194680", "title": "Chemotherapy of disseminated breast cancer. Current status and prospects.", "content": "Chemotherapy once relegated to end stage patients has markedly improved with the use of combinations. Response rates with single agents have improved from 15 to 35%, to 50 to 70%, using combinations with an increase in complete response rates to about 25%. A series of four studies completed by the Eastern Cooperative Oncology Group over the past eight years typifies the improvement in response rates achieved by combinations as compared to single agents. Survival gain can be demonstrated for responders vs non-responders; however with current combinations, there is an apparent plateau in response rates (55 to 60%), durations of response (eight months) and survival for responders (18-22 months) as compared to survival of non-responders (six to eight months). Further improvement in response rates may occur by searching for new agents, combining hormonal and immunostimulation with chemotherapy or by sequencing non-crossresistant combinations. However, since most patients with breast cancer present with local or regional disease but go on to die of disseminated cancer, major improvements in survival are most likely to occur by treating this neoplasm as a systemic disease through cobmining effective local therapy with systemic treatments.", "contents": "Chemotherapy of disseminated breast cancer. Current status and prospects. Chemotherapy once relegated to end stage patients has markedly improved with the use of combinations. Response rates with single agents have improved from 15 to 35%, to 50 to 70%, using combinations with an increase in complete response rates to about 25%. A series of four studies completed by the Eastern Cooperative Oncology Group over the past eight years typifies the improvement in response rates achieved by combinations as compared to single agents. Survival gain can be demonstrated for responders vs non-responders; however with current combinations, there is an apparent plateau in response rates (55 to 60%), durations of response (eight months) and survival for responders (18-22 months) as compared to survival of non-responders (six to eight months). Further improvement in response rates may occur by searching for new agents, combining hormonal and immunostimulation with chemotherapy or by sequencing non-crossresistant combinations. However, since most patients with breast cancer present with local or regional disease but go on to die of disseminated cancer, major improvements in survival are most likely to occur by treating this neoplasm as a systemic disease through cobmining effective local therapy with systemic treatments."}
{"id": "PMID:194681", "title": "Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer.", "content": "Approximately one-third of patients with metastatic breast carcinoma respond to surgical ablative therapy but the morbidity associated with these procedures has limited their use to highly selected patients. Consequently, a chemical method of adrenal suppression was developed using a potent inhibitor of adrenal steroid synthesis, aminoglutethimide, in combination with a synthetic glucocorticoid, dexamethasone. While this regimen effectively blocked adrenal function, it was complicated by a drug interaction in which aminoglutethimide accelerated the metabolism and reduced the bioavailability of dexamethasone. To overcome this problem, a new regime using aminoglutethimide and hydrocortisone, a glucocorticoid less susceptible to altered metabolism, was developed. Kinetic studies confirmed that aminoglutethimide does not interact with hydrocortisone to alter its rate of metabolism. Hormone measurements established that 1000 mg of aminoglutethimide and 40 mg of hydrocortisone daily suppressed DHA-sulfate, androstenedione, estrone, estradiol and aldosterone to a greater extent than the prior protocol using aminoglutethimide and 2-3 mg of dexamethasone. Patients experienced objective tumor regression with equal frequency while receiving the aminoglutethimide-hydrocortisone regimen or aminoglutethimide and dexamethasone and the overall rate of response in 50 evaluable patients was 38%. Side effects occurred frequently in the first few weeks of treatment but disappeared nearly uniformly thereafter. The present aminoglutethimide-hydrocortisone regimen is simple, non-toxic, effective in inhibiting estradiol synthesis and capable of inducing tumor regression as frequently as previously reported with adrenalectomy.", "contents": "Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer. Approximately one-third of patients with metastatic breast carcinoma respond to surgical ablative therapy but the morbidity associated with these procedures has limited their use to highly selected patients. Consequently, a chemical method of adrenal suppression was developed using a potent inhibitor of adrenal steroid synthesis, aminoglutethimide, in combination with a synthetic glucocorticoid, dexamethasone. While this regimen effectively blocked adrenal function, it was complicated by a drug interaction in which aminoglutethimide accelerated the metabolism and reduced the bioavailability of dexamethasone. To overcome this problem, a new regime using aminoglutethimide and hydrocortisone, a glucocorticoid less susceptible to altered metabolism, was developed. Kinetic studies confirmed that aminoglutethimide does not interact with hydrocortisone to alter its rate of metabolism. Hormone measurements established that 1000 mg of aminoglutethimide and 40 mg of hydrocortisone daily suppressed DHA-sulfate, androstenedione, estrone, estradiol and aldosterone to a greater extent than the prior protocol using aminoglutethimide and 2-3 mg of dexamethasone. Patients experienced objective tumor regression with equal frequency while receiving the aminoglutethimide-hydrocortisone regimen or aminoglutethimide and dexamethasone and the overall rate of response in 50 evaluable patients was 38%. Side effects occurred frequently in the first few weeks of treatment but disappeared nearly uniformly thereafter. The present aminoglutethimide-hydrocortisone regimen is simple, non-toxic, effective in inhibiting estradiol synthesis and capable of inducing tumor regression as frequently as previously reported with adrenalectomy."}
{"id": "PMID:194683", "title": "Gonadotropin receptors in experimentally induced ovarian tumors in mice.", "content": "Gonadotropic hormones are required for the induction and maintenance of tumors arising in ovaries that have been transplanted to the spleens of gonadectomized mice. The characteristics of gonadotropin receptors for human chorionic gonadotropin (HCG)-luteinizing hormone on cells from these tumors of varying size, age, and morphology have been determined. The specific binding of 125I-labeled HCG to cells obtained by collagenase digestion, 15 to 65 weeks postimplantation from granulosa cell or luteinized cell, or mixed granulosa-luteal tumors was analyzed by Scatchard plot. Neither the size, weight, duration of implantation, nor histological morphology affected the receptor-binding affinity [equilibrium dissociation constant (Kd), 6 X 10(-10) M], and, presumably, the receptor is qualitatively similar. In contrast, the number of HCG receptors per cell increased 17-fold and was related to the degree of morphological luteinization of the tumor. HCG-sensitive adenyl cyclase was also demonstrated and compared to HCG binding in a highly luteinized tumor.", "contents": "Gonadotropin receptors in experimentally induced ovarian tumors in mice. Gonadotropic hormones are required for the induction and maintenance of tumors arising in ovaries that have been transplanted to the spleens of gonadectomized mice. The characteristics of gonadotropin receptors for human chorionic gonadotropin (HCG)-luteinizing hormone on cells from these tumors of varying size, age, and morphology have been determined. The specific binding of 125I-labeled HCG to cells obtained by collagenase digestion, 15 to 65 weeks postimplantation from granulosa cell or luteinized cell, or mixed granulosa-luteal tumors was analyzed by Scatchard plot. Neither the size, weight, duration of implantation, nor histological morphology affected the receptor-binding affinity [equilibrium dissociation constant (Kd), 6 X 10(-10) M], and, presumably, the receptor is qualitatively similar. In contrast, the number of HCG receptors per cell increased 17-fold and was related to the degree of morphological luteinization of the tumor. HCG-sensitive adenyl cyclase was also demonstrated and compared to HCG binding in a highly luteinized tumor."}
{"id": "PMID:194684", "title": "Effect of somatostatin on growth hormone release by MtT-F4 rat pituitary tumor in vitro.", "content": "Fluoride-stimulated adenylate cyclase is demonstrated inisolated tumor cells of transplantable rat pituitary tumor MtT-F4 in vitro. The intracellular cyclic adenosine 3':5'-monophosphate is lowered in the cells incubated in the presence of synthetic somatostatin. Contrary to the findings reported for normal pituitary, however, the immunoreactive growth hormone release does not change when either somatostatin or phosphodiesterase inhibitors are present in the incubation medium. The presence of dibutyryl cyclic adenosine 3':5'-monophosphate (5 mM) in the incubation medium does not change the rate of growth hormone release by isolated tumor cells.", "contents": "Effect of somatostatin on growth hormone release by MtT-F4 rat pituitary tumor in vitro. Fluoride-stimulated adenylate cyclase is demonstrated inisolated tumor cells of transplantable rat pituitary tumor MtT-F4 in vitro. The intracellular cyclic adenosine 3':5'-monophosphate is lowered in the cells incubated in the presence of synthetic somatostatin. Contrary to the findings reported for normal pituitary, however, the immunoreactive growth hormone release does not change when either somatostatin or phosphodiesterase inhibitors are present in the incubation medium. The presence of dibutyryl cyclic adenosine 3':5'-monophosphate (5 mM) in the incubation medium does not change the rate of growth hormone release by isolated tumor cells."}
{"id": "PMID:194689", "title": "Epidemiologic study of prostatic cancer: preliminary report.", "content": "In a preliminary report on a small fraction of the projected subject population, some evidence in support of both sexual activity and venereal transmission hypotheses is accumulating. Prostatic cancer cases, in contrast to hospitalized and/or neighborhood controls, are beginning to show greater proportions of selected sexual activities compatible with venereal transmission of an infectious agent, such as number of sexual partners, use of prostitutes, prior venereal disease, and genital infections in the spouse. Patients with prostatic cancer also appear to have had higher fertility and more prostatic cancer in blood relatives than controls. Age at first intercourse and at first marriage are lower among the cancer patients than among the controls. Antibody titrations for herpesvirus and cytomegalic virus, although currently not revealing striking disparities in positivity, tend to show higher titers among the cancer cases.", "contents": "Epidemiologic study of prostatic cancer: preliminary report. In a preliminary report on a small fraction of the projected subject population, some evidence in support of both sexual activity and venereal transmission hypotheses is accumulating. Prostatic cancer cases, in contrast to hospitalized and/or neighborhood controls, are beginning to show greater proportions of selected sexual activities compatible with venereal transmission of an infectious agent, such as number of sexual partners, use of prostitutes, prior venereal disease, and genital infections in the spouse. Patients with prostatic cancer also appear to have had higher fertility and more prostatic cancer in blood relatives than controls. Age at first intercourse and at first marriage are lower among the cancer patients than among the controls. Antibody titrations for herpesvirus and cytomegalic virus, although currently not revealing striking disparities in positivity, tend to show higher titers among the cancer cases."}
{"id": "PMID:194691", "title": "Intensive chemotherapy of small cell bronchogenic carcinoma.", "content": "Thirty-two patients (27, extensive disease; five, regional disease) with histologically documented small cell carcinoma entered a randomized study to determine the efficacy of intensive induction chemotherapy. The necessity of a protected environment (laminar air flow room) during this treatment was also evaluated. Patients received high-dose or standard-dose cyclophosphamide, methotrexate, and CCNU (CMC) during the first 6 weeks of treatment. Subsequent maintenance therapy consisted of standard-dose CMC until disease progression. In 23 patients treated with high-dose chemotherapy there were responses in 96% (30% complete). Standard-dose chemotherapy gave responses in 45%, none of which were complete. Median survival correlated with completeness of response and was 16+ months for the seven complete responders. Patients receiving high-dose CMC spent an average of 10 days with neutrophil counts less than 1000/mm3. There was only one documented, non-fatal infection. High-dose chemotherapy gives better responses and longer survival than previously utilized standard doses of the same drugs. Patients could safely be treated in the hospital ward.", "contents": "Intensive chemotherapy of small cell bronchogenic carcinoma. Thirty-two patients (27, extensive disease; five, regional disease) with histologically documented small cell carcinoma entered a randomized study to determine the efficacy of intensive induction chemotherapy. The necessity of a protected environment (laminar air flow room) during this treatment was also evaluated. Patients received high-dose or standard-dose cyclophosphamide, methotrexate, and CCNU (CMC) during the first 6 weeks of treatment. Subsequent maintenance therapy consisted of standard-dose CMC until disease progression. In 23 patients treated with high-dose chemotherapy there were responses in 96% (30% complete). Standard-dose chemotherapy gave responses in 45%, none of which were complete. Median survival correlated with completeness of response and was 16+ months for the seven complete responders. Patients receiving high-dose CMC spent an average of 10 days with neutrophil counts less than 1000/mm3. There was only one documented, non-fatal infection. High-dose chemotherapy gives better responses and longer survival than previously utilized standard doses of the same drugs. Patients could safely be treated in the hospital ward."}
{"id": "PMID:194696", "title": "Properties of the H-4-II-E tumor cell system. I. Growth and cell proliferation kinetics of an experimental hepatoma.", "content": "Growth and cell proliferation kinetics of hepatoma H-4-II-E and its tissue culture derivative have been studied to establish the characteristics of an in vivo--in vitro solid tumor model. The H-4-II-E line, originating from the Reuber H-35 hepatoma, can be maintained and studied either in cell culture or as a transplantable solid tumor in ACI male rats. In addition it allows for the in vitro assay of cell survival following treatment of animal tumors in situ. In vivo, hepatoma H-4-II-E is rapidly growing tumor with a mean doubling time of 49-2 hr. The cell cyle time is 39-1 hr with a cell loss factor of 0-32. Retrospective examination of tumor specimens obtained during the establishment of the H-4-II-E tumor system demonstrates that both structural as well as cell population changes have occurred. The biological characteristics of the primary tumor (H-35) and an early intermediate stage (H-35tc2) are compared with H-4-II-E and the histopathological, growth and cell kinetic changes are discussed.", "contents": "Properties of the H-4-II-E tumor cell system. I. Growth and cell proliferation kinetics of an experimental hepatoma. Growth and cell proliferation kinetics of hepatoma H-4-II-E and its tissue culture derivative have been studied to establish the characteristics of an in vivo--in vitro solid tumor model. The H-4-II-E line, originating from the Reuber H-35 hepatoma, can be maintained and studied either in cell culture or as a transplantable solid tumor in ACI male rats. In addition it allows for the in vitro assay of cell survival following treatment of animal tumors in situ. In vivo, hepatoma H-4-II-E is rapidly growing tumor with a mean doubling time of 49-2 hr. The cell cyle time is 39-1 hr with a cell loss factor of 0-32. Retrospective examination of tumor specimens obtained during the establishment of the H-4-II-E tumor system demonstrates that both structural as well as cell population changes have occurred. The biological characteristics of the primary tumor (H-35) and an early intermediate stage (H-35tc2) are compared with H-4-II-E and the histopathological, growth and cell kinetic changes are discussed."}
{"id": "PMID:194697", "title": "Properties of the H-4-II-E tumor cell system. II. In vitro characteristics of an experimental tumor cell line.", "content": "The growth and cell proliferation characteristics of the H-4-II-E cell line, giving rise to hepatoma H-4-II-E when inoculated into male ACI rats, were studied in vitro. Following seedling of 2 x 10(5) cells into culture dishes, exponential cell growth occurs in cultures fed both at 24 hr and 48 hr intervals with a population doubling time of 18-4 hr. Plateau phase growth conditions are established on day 7 and day 5 for cultures fed at 24 hr and 48 hr intervals respectively. Both the plateau phase cell density and the maintenance of plateau phase appear dependent on the frequency of feeding. For cultures fed daily, the transition from exponetial growth to plateau phase results from both a reduction in the number of proliferating cells (99% v. 35%) as well as an elongation of the cell cycle (17-7 hr v. 128-4 hr). The cell proliferation characteristics of the culture are further discussed in reference to both cell growth and feeding schedules of other cell lines.", "contents": "Properties of the H-4-II-E tumor cell system. II. In vitro characteristics of an experimental tumor cell line. The growth and cell proliferation characteristics of the H-4-II-E cell line, giving rise to hepatoma H-4-II-E when inoculated into male ACI rats, were studied in vitro. Following seedling of 2 x 10(5) cells into culture dishes, exponential cell growth occurs in cultures fed both at 24 hr and 48 hr intervals with a population doubling time of 18-4 hr. Plateau phase growth conditions are established on day 7 and day 5 for cultures fed at 24 hr and 48 hr intervals respectively. Both the plateau phase cell density and the maintenance of plateau phase appear dependent on the frequency of feeding. For cultures fed daily, the transition from exponetial growth to plateau phase results from both a reduction in the number of proliferating cells (99% v. 35%) as well as an elongation of the cell cycle (17-7 hr v. 128-4 hr). The cell proliferation characteristics of the culture are further discussed in reference to both cell growth and feeding schedules of other cell lines."}
{"id": "PMID:194698", "title": "Modulation of in vitro erythropoiesis: enhancement of erythroid colony growth by cyclic nucleotides.", "content": "Mammalian erythropoiesis, as assayed by erythroid colony formation in vitro, is enhanced by cyclic adenosine nucleotides and agents which are capable of raising intracellular cyclic AMP (cAMP) levels. With canine marrow cells as target, this enhancement was shown to be specific for cAMP and its mono- and dibutyryl derivatives. Adenosine and its derivatives, such as AMP, ADP and ATP, and other cyclic nucleotides, such as cGMP, dibutyryl-cGMP, cCMP and cIMP and sodium butyrate were inactive. The phosphodiesterase inhibitor, RO-20-1724, and the adenyl cyclase stimulator, cholera enterotoxin, both markedly increased colony numbers. Studies with tritiated thymidine showed that about 50% of the cells responding to either erythropoietin (ESF) or dibutyryl cAMP (db-cAMP) were in DNA synthesis. However, by unit gravity sedimentation velocity analysis, the peak of ESF-responsive colony forming cells sedimented more rapidly (8-7 +/- 0-2 mm/hr) than the peak of db-cAMP-responsive cells (7-5 +/- 0 mm/hr). These results demonstrate that adenyl cyclase-linked mechanisms influence in vitro erythropoietic proliferation and suggest that other hormones and simple molecules might interact with surface receptors and thus modulate the action of ESF at the cellular level.", "contents": "Modulation of in vitro erythropoiesis: enhancement of erythroid colony growth by cyclic nucleotides. Mammalian erythropoiesis, as assayed by erythroid colony formation in vitro, is enhanced by cyclic adenosine nucleotides and agents which are capable of raising intracellular cyclic AMP (cAMP) levels. With canine marrow cells as target, this enhancement was shown to be specific for cAMP and its mono- and dibutyryl derivatives. Adenosine and its derivatives, such as AMP, ADP and ATP, and other cyclic nucleotides, such as cGMP, dibutyryl-cGMP, cCMP and cIMP and sodium butyrate were inactive. The phosphodiesterase inhibitor, RO-20-1724, and the adenyl cyclase stimulator, cholera enterotoxin, both markedly increased colony numbers. Studies with tritiated thymidine showed that about 50% of the cells responding to either erythropoietin (ESF) or dibutyryl cAMP (db-cAMP) were in DNA synthesis. However, by unit gravity sedimentation velocity analysis, the peak of ESF-responsive colony forming cells sedimented more rapidly (8-7 +/- 0-2 mm/hr) than the peak of db-cAMP-responsive cells (7-5 +/- 0 mm/hr). These results demonstrate that adenyl cyclase-linked mechanisms influence in vitro erythropoietic proliferation and suggest that other hormones and simple molecules might interact with surface receptors and thus modulate the action of ESF at the cellular level."}
{"id": "PMID:194699", "title": "Relationships between membranous organelles in amoebae studied by electron microscopic cytochemical staining.", "content": "The intracellular location of a variety of enzymes was studied in Amoeba proteus with the use of electron microscopic cytochemical methods, in an attempt to assess the relationships between different membranous organelles. One group of enzymes, including nucleoside diphosphatases (IDPase, UDPase, GDPase, ADPase), carbamoyl phosphatase, alkaline phosphatase, and BAXD oxidase was localized mainly in the rough endoplasmic reticulum, nuclear envelope, and convex side of the Golgi apparatus. Esterase activity had a similar localization except that the Golgi apparatus was \"stained\" throughout most of its extent. A second group of enzymes was found in Golgi cisternae and vesicles, and in come vacuoles. This group included acid phosphatase, thiamine pyrophosphatase, and aryl sulfatase. Some enzymes previously detected in cytoplasmic membranes of other cells, including glucose-6-phosphatase, showed little or no activity in amoebae. The results suggest that there are chemical similarities and probable functional relationships between the rough endoplasmic reticulum, the nuclear envelope, and the convex side of the Golgi apparatus. On the other hand, the concave pole of the Golgi apparatus, aggregates of smooth tubules and vesicles, and the cell surface appear more closely related to one another than to the endoplasmic reticulum and the convex side of the Golgi apparatus. The cytochemical similarity between the Golgi apparatus and certain vacuoles such as food vacuoles may reflect the role of the Golgi apparatus in the formation of lysosomes. The locations of reaction products of the various enzymes in amoebae are compared with observations reported for other cell types.", "contents": "Relationships between membranous organelles in amoebae studied by electron microscopic cytochemical staining. The intracellular location of a variety of enzymes was studied in Amoeba proteus with the use of electron microscopic cytochemical methods, in an attempt to assess the relationships between different membranous organelles. One group of enzymes, including nucleoside diphosphatases (IDPase, UDPase, GDPase, ADPase), carbamoyl phosphatase, alkaline phosphatase, and BAXD oxidase was localized mainly in the rough endoplasmic reticulum, nuclear envelope, and convex side of the Golgi apparatus. Esterase activity had a similar localization except that the Golgi apparatus was \"stained\" throughout most of its extent. A second group of enzymes was found in Golgi cisternae and vesicles, and in come vacuoles. This group included acid phosphatase, thiamine pyrophosphatase, and aryl sulfatase. Some enzymes previously detected in cytoplasmic membranes of other cells, including glucose-6-phosphatase, showed little or no activity in amoebae. The results suggest that there are chemical similarities and probable functional relationships between the rough endoplasmic reticulum, the nuclear envelope, and the convex side of the Golgi apparatus. On the other hand, the concave pole of the Golgi apparatus, aggregates of smooth tubules and vesicles, and the cell surface appear more closely related to one another than to the endoplasmic reticulum and the convex side of the Golgi apparatus. The cytochemical similarity between the Golgi apparatus and certain vacuoles such as food vacuoles may reflect the role of the Golgi apparatus in the formation of lysosomes. The locations of reaction products of the various enzymes in amoebae are compared with observations reported for other cell types."}
{"id": "PMID:194700", "title": "Developmental immunohistology of melanotrophs in Xenopus laevis tadpoles.", "content": "The adenohypophysial primordium of Xenopus laevis tadpoles at stages 33/34 to 46 (Nieuwkoop and Faber, 1956) were examined immunohistologically for alpha-MSH, beta-MSH and ACTH. beta-MSH was demonstrated from stage 37/38 onwards, and alpha-MSH from stage 39. No signs of ACTH production were detected. alpha-MSH and beta-MSH occurred in the same cells. No differences were found in the intensity of immunofluorescence between tadpoles which were kept on a black and a white background. The present study lends no support to the hypothesis concerning the derivation of alpha-MSH from ACTH. The observations made suggest that the morphological formation of the pars intermedia is accomplished during stages 37/38 to 39.", "contents": "Developmental immunohistology of melanotrophs in Xenopus laevis tadpoles. The adenohypophysial primordium of Xenopus laevis tadpoles at stages 33/34 to 46 (Nieuwkoop and Faber, 1956) were examined immunohistologically for alpha-MSH, beta-MSH and ACTH. beta-MSH was demonstrated from stage 37/38 onwards, and alpha-MSH from stage 39. No signs of ACTH production were detected. alpha-MSH and beta-MSH occurred in the same cells. No differences were found in the intensity of immunofluorescence between tadpoles which were kept on a black and a white background. The present study lends no support to the hypothesis concerning the derivation of alpha-MSH from ACTH. The observations made suggest that the morphological formation of the pars intermedia is accomplished during stages 37/38 to 39."}
{"id": "PMID:194701", "title": "Morphological aspects of the hypothalamic-hypophyseal system. VII. The tanycytes: Their relation to the hypophyseal adrenocorticotrophic function. An ultrastructural study.", "content": "The ultrastruct of the tanycyte ependyma in male 160-180 g Wistar albino rats was studied under normal conditions and in experiments involving long-term suppression of ACTH secretion and its long-term stimulation. The former was accomplished by daily (for 8 days) intraperitoneal administration of dexamethasone phosphate at low (5 microgram/100 g) and high (100 microgram/100 g) concentrations. The effectiveness of suppression of the hypothalamic-hypophyseal-adrenal system in the experimental animals was judged by their reaction to two-minute ether stress (determination of plasma corticosterone) and by the results of measurement of the adrenal weights. Stimulation of ACTH secretion was achieved by bilateral adrenalectomy; the animals were examined on days 8, 10, 14, and 22 following the operation. The results obtained were in agreement with the previously established fact that there is a negative correlation between tanycyte activity and hypophyseal adrenocorticotropic function (Akmayed and Fidelina, 1974). They also testified to the predominant involvement of the median eminence tanycyte ependyma (beta-tanycytes according to the author's nomenclature) in these relationships. It is supposed that correlations are regulated by a feedback mechanism and attest to the involvement of beta-tanycytes in the inhibiting control of hypophyseal adrenocorticotrophic function. The mechanism of this control may be explained alternatively: either the tanycytes transport ACTH-suppression substances (catecholamines, corticosteroids, ACTH) from the CSF to the hypophyseal portal system or they themselves secrete substances possessing ACTH-suppressive activity. The authors distinguish several types of vesicles in the beta-tanycytes, the number of which changed with experimentally induced shifts in hypophyseal adrenocorticotrophic function. These vesicles are discussed in connection with the transport and secretory activity of the tanycytes and are considered to be a possible substrate of the hypothalamic inhibiting effect on ACTH secretion.", "contents": "Morphological aspects of the hypothalamic-hypophyseal system. VII. The tanycytes: Their relation to the hypophyseal adrenocorticotrophic function. An ultrastructural study. The ultrastruct of the tanycyte ependyma in male 160-180 g Wistar albino rats was studied under normal conditions and in experiments involving long-term suppression of ACTH secretion and its long-term stimulation. The former was accomplished by daily (for 8 days) intraperitoneal administration of dexamethasone phosphate at low (5 microgram/100 g) and high (100 microgram/100 g) concentrations. The effectiveness of suppression of the hypothalamic-hypophyseal-adrenal system in the experimental animals was judged by their reaction to two-minute ether stress (determination of plasma corticosterone) and by the results of measurement of the adrenal weights. Stimulation of ACTH secretion was achieved by bilateral adrenalectomy; the animals were examined on days 8, 10, 14, and 22 following the operation. The results obtained were in agreement with the previously established fact that there is a negative correlation between tanycyte activity and hypophyseal adrenocorticotropic function (Akmayed and Fidelina, 1974). They also testified to the predominant involvement of the median eminence tanycyte ependyma (beta-tanycytes according to the author's nomenclature) in these relationships. It is supposed that correlations are regulated by a feedback mechanism and attest to the involvement of beta-tanycytes in the inhibiting control of hypophyseal adrenocorticotrophic function. The mechanism of this control may be explained alternatively: either the tanycytes transport ACTH-suppression substances (catecholamines, corticosteroids, ACTH) from the CSF to the hypophyseal portal system or they themselves secrete substances possessing ACTH-suppressive activity. The authors distinguish several types of vesicles in the beta-tanycytes, the number of which changed with experimentally induced shifts in hypophyseal adrenocorticotrophic function. These vesicles are discussed in connection with the transport and secretory activity of the tanycytes and are considered to be a possible substrate of the hypothalamic inhibiting effect on ACTH secretion."}
{"id": "PMID:194702", "title": "Cyclic AMP-induced cytolysis in S49 cells: selection of an unresponsive \"deathless\" mutant.", "content": "Wild-type S49 lymphoma cells respond to cyclic adenosine 3', 5'-monophosphate (cAMP) by inducing cAMP phosphodiesterase, halting growth in the G1 phase of the cell cycle and subsequently dying. By using a counter selection procedure, we have isolated a new class of mutants of S49 cells termed \"deathless\" that are resistant to cytolysis, but otherwise respond like the wild-type cells to cAMP. Upon removal of the cyclic nucleotide, D-cells resume their normal growth. Unlike all other cAMP-resistant mutants of S49 cells isolated until now, the D- mutant has a functionally normal cAMP-dependent protein kinase and retains normal ability to induce phosphodiesterase and arrest cell growth in G1. It is probable that the altered gene product of the D- mutant is distal to protein kinase and in a biochemical pathway separate from that of cAMP induction of phosphodiesterase or growth arrest. The D- mutant may facilitate studies of the mechanism of cAMP-induced cytolysis and growth regulation in S49 cells.", "contents": "Cyclic AMP-induced cytolysis in S49 cells: selection of an unresponsive \"deathless\" mutant. Wild-type S49 lymphoma cells respond to cyclic adenosine 3', 5'-monophosphate (cAMP) by inducing cAMP phosphodiesterase, halting growth in the G1 phase of the cell cycle and subsequently dying. By using a counter selection procedure, we have isolated a new class of mutants of S49 cells termed \"deathless\" that are resistant to cytolysis, but otherwise respond like the wild-type cells to cAMP. Upon removal of the cyclic nucleotide, D-cells resume their normal growth. Unlike all other cAMP-resistant mutants of S49 cells isolated until now, the D- mutant has a functionally normal cAMP-dependent protein kinase and retains normal ability to induce phosphodiesterase and arrest cell growth in G1. It is probable that the altered gene product of the D- mutant is distal to protein kinase and in a biochemical pathway separate from that of cAMP induction of phosphodiesterase or growth arrest. The D- mutant may facilitate studies of the mechanism of cAMP-induced cytolysis and growth regulation in S49 cells."}
{"id": "PMID:194703", "title": "Developmentally regulated cyclic AMP-dependent protein kinases in Dictyostelium discoideum.", "content": "Two apparently distinct species of cyclic AMP-dependent protein kinase appear during the first 1-2 hr of development in Dictyostelium discoideum; no such activity can be detected in vegetative cell extracts. These two kinases are similar in properties to the type I and II cyclic AMP-dependent protein kinases found in a number of mammalian tissues. Their time of appearance supports the idea that one or both mediate the effects of cyclic AMP on gene expression early in Dictyostelium development.", "contents": "Developmentally regulated cyclic AMP-dependent protein kinases in Dictyostelium discoideum. Two apparently distinct species of cyclic AMP-dependent protein kinase appear during the first 1-2 hr of development in Dictyostelium discoideum; no such activity can be detected in vegetative cell extracts. These two kinases are similar in properties to the type I and II cyclic AMP-dependent protein kinases found in a number of mammalian tissues. Their time of appearance supports the idea that one or both mediate the effects of cyclic AMP on gene expression early in Dictyostelium development."}
{"id": "PMID:194705", "title": "Biochemical transformation of mouse cells by fragments of herpes simplex virus DNA.", "content": "Mouse L cells lacking the enzyme thymidine kinase (LMTK-) have been converted to a TK+ phenotype by infection with fragmented HSV2 strain 333 DNA. The DNA fragments used were either unique, produced by cleavage with the restriction endonucleases Eco RI and Hild III, or randomly produced by mechanical shearing. Survival in HAT medium was used initially to establish the TK+ phenotype; clones possessing the ability to grow in selective medium were picked on the basis of differing morphology and growth rates. Cytosol extracts of these clones possessed virus-specified TK activity identical to that present in cells lytically infected with HSV2, as indicated by thermolability and mobility on polyacrylamide gel electrophoresis. The transformed cells also exhibit HSV-specific immunofluorescence. Based on these transformation studies, it is possible to assign a map location to the TK gene on the HSV genome.", "contents": "Biochemical transformation of mouse cells by fragments of herpes simplex virus DNA. Mouse L cells lacking the enzyme thymidine kinase (LMTK-) have been converted to a TK+ phenotype by infection with fragmented HSV2 strain 333 DNA. The DNA fragments used were either unique, produced by cleavage with the restriction endonucleases Eco RI and Hild III, or randomly produced by mechanical shearing. Survival in HAT medium was used initially to establish the TK+ phenotype; clones possessing the ability to grow in selective medium were picked on the basis of differing morphology and growth rates. Cytosol extracts of these clones possessed virus-specified TK activity identical to that present in cells lytically infected with HSV2, as indicated by thermolability and mobility on polyacrylamide gel electrophoresis. The transformed cells also exhibit HSV-specific immunofluorescence. Based on these transformation studies, it is possible to assign a map location to the TK gene on the HSV genome."}
{"id": "PMID:194706", "title": "Suppression of replication of SV40 and polyoma virus in mouse-human hybrids.", "content": "Mouse-human heterokaryons are permissive for the replication of both SV40 virus and polyoma virus. If the hybrids which develop from these heterokaryons segregate human chromosomes (mouse greater than human hybrids), the hybrids are permissive for replication of polyoma virus but not for replication of SV40 virus. If the subsequent hybrids segregate mouse chromosomes (human greater than mouse hybrids), such hybrids support the replication of SV40 virus but not the replication of polyoma virus, even when the hybrids contain at least one copy of each mouse chromosome. This indicates that during the transition from heterokaryon to hybrid cell, suppression of expression of species-specific function(s) required for the replication of these species-specific viruses occurs in parallel with the direction of chromosome loss and suppression of nucleolus organizer activity.", "contents": "Suppression of replication of SV40 and polyoma virus in mouse-human hybrids. Mouse-human heterokaryons are permissive for the replication of both SV40 virus and polyoma virus. If the hybrids which develop from these heterokaryons segregate human chromosomes (mouse greater than human hybrids), the hybrids are permissive for replication of polyoma virus but not for replication of SV40 virus. If the subsequent hybrids segregate mouse chromosomes (human greater than mouse hybrids), such hybrids support the replication of SV40 virus but not the replication of polyoma virus, even when the hybrids contain at least one copy of each mouse chromosome. This indicates that during the transition from heterokaryon to hybrid cell, suppression of expression of species-specific function(s) required for the replication of these species-specific viruses occurs in parallel with the direction of chromosome loss and suppression of nucleolus organizer activity."}
{"id": "PMID:194709", "title": "Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail.", "content": "Several continuous tissue culture cell lines were established from methylcholanthrene-induced fibrosarcomas of Japanese quail. The lines consist either of fibroblastic elements, round refractile cells or polygonal cells. They show transformed characteristics in agar colony formation and hexose uptake, and most are tumorigenic. Their cloning efficiency in plastic dishes is not increased over that of normal quail embryo fibroblasts. The quail tumor cell lines do not produce endogenous avian oncoviruses and fail to complement the Bryan high titer strain of Rous sarcoma virus; those tested lack the p27 protein of avian oncoviruses. Most of the cell lines are susceptible to subgroup A avian sarcoma viruses, but are relatively resistant to viruses of subgroups C, E and F as compared to normal quail embryo fibroblasts.", "contents": "Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail. Several continuous tissue culture cell lines were established from methylcholanthrene-induced fibrosarcomas of Japanese quail. The lines consist either of fibroblastic elements, round refractile cells or polygonal cells. They show transformed characteristics in agar colony formation and hexose uptake, and most are tumorigenic. Their cloning efficiency in plastic dishes is not increased over that of normal quail embryo fibroblasts. The quail tumor cell lines do not produce endogenous avian oncoviruses and fail to complement the Bryan high titer strain of Rous sarcoma virus; those tested lack the p27 protein of avian oncoviruses. Most of the cell lines are susceptible to subgroup A avian sarcoma viruses, but are relatively resistant to viruses of subgroups C, E and F as compared to normal quail embryo fibroblasts."}
{"id": "PMID:194718", "title": "Similarities of two hepatitis A virus strains.", "content": "In outbreaks of type A hepatitis in Los Angeles, USA, and Rosario, Argentina, virus particles were isolated from faeces. The geographically diverse strains were identical in appearance and serological reactivity. They differed only in buoyant density, but other workers have also obtained inconsistent results in estimating this. We conclude that the virus strains in the two epidemics were identical.", "contents": "Similarities of two hepatitis A virus strains. In outbreaks of type A hepatitis in Los Angeles, USA, and Rosario, Argentina, virus particles were isolated from faeces. The geographically diverse strains were identical in appearance and serological reactivity. They differed only in buoyant density, but other workers have also obtained inconsistent results in estimating this. We conclude that the virus strains in the two epidemics were identical."}
{"id": "PMID:194719", "title": "[Degradation by phytohemagglutinin of the antiviral state induced by interferon].", "content": "Phytohaemagglutinin (PHA M and P forms), when added to L 929 cells previously treated by murine interferon, degrades the antiviral state and restores virus sensitivity in the cells. This degradation depends on the amount of the lectin, the contact period with the cell and the presence of PHA membrane receptors. The importance of membrane configuration not only in the induction but also in the maintenance of the antiviral state is discussed.", "contents": "[Degradation by phytohemagglutinin of the antiviral state induced by interferon]. Phytohaemagglutinin (PHA M and P forms), when added to L 929 cells previously treated by murine interferon, degrades the antiviral state and restores virus sensitivity in the cells. This degradation depends on the amount of the lectin, the contact period with the cell and the presence of PHA membrane receptors. The importance of membrane configuration not only in the induction but also in the maintenance of the antiviral state is discussed."}
{"id": "PMID:194720", "title": "[Ontogenetic analysis of the theta rhythm during paradoxical sleep in rats].", "content": "In the rat, an ontogenetic study of theta rhythm during paradoxical sleep shows a clear evolution between the 14th and the 30th postnatal day. During this period, its mean frequency increases from 5 to 7 cycles per second, and its spectrum shows significant changes. These parameters (mean frequency and spectral components) of the theta rhythm could be a useful index of brain maturation in the rat.", "contents": "[Ontogenetic analysis of the theta rhythm during paradoxical sleep in rats]. In the rat, an ontogenetic study of theta rhythm during paradoxical sleep shows a clear evolution between the 14th and the 30th postnatal day. During this period, its mean frequency increases from 5 to 7 cycles per second, and its spectrum shows significant changes. These parameters (mean frequency and spectral components) of the theta rhythm could be a useful index of brain maturation in the rat."}
{"id": "PMID:194721", "title": "[Transformation, in vitro, of cerebral hamster cells by polyoma virus].", "content": "A cell line called HCxPy was obtained in vitro by transformation of dissociated hamster brain cell cultures by polyoma virus. The first foci of transformed cells became evident 90 to 120 days after viral infection. This cell line is now at the 46th passage. The cells appear tumorigenic for hamsters after subcutaneous and intracerebral injection. They carry the polyoma virus T and cell surface antigens. Good evidence for astrocytic differentiation can be found by morphological examination of the tumours and of the cultured cells.", "contents": "[Transformation, in vitro, of cerebral hamster cells by polyoma virus]. A cell line called HCxPy was obtained in vitro by transformation of dissociated hamster brain cell cultures by polyoma virus. The first foci of transformed cells became evident 90 to 120 days after viral infection. This cell line is now at the 46th passage. The cells appear tumorigenic for hamsters after subcutaneous and intracerebral injection. They carry the polyoma virus T and cell surface antigens. Good evidence for astrocytic differentiation can be found by morphological examination of the tumours and of the cultured cells."}
{"id": "PMID:194722", "title": "[Does the diabetes caused by viral infection in mice depend on immune reactions?].", "content": "Normal DBA2 mice become highly diabetic after infection with the EMC virus. But 500 R X-irradiation before infection inhibits the increase of mean blood glucose levels thus indicating the participation of immune reactions in the appearance of diabetes.", "contents": "[Does the diabetes caused by viral infection in mice depend on immune reactions?]. Normal DBA2 mice become highly diabetic after infection with the EMC virus. But 500 R X-irradiation before infection inhibits the increase of mean blood glucose levels thus indicating the participation of immune reactions in the appearance of diabetes."}
{"id": "PMID:194723", "title": "[Desensitization by human chorionic gonadotropin (hCG): demonstration of a negative control of gonadotropin receptors by hCG at the level of testicular Leydig cells].", "content": "A single injection of hCG (500 IU) to intact and hypophysectomized prepubertal rat increases plasma testosterone levels and decreases hCG receptors in the testicular Leydig cells for 4 to 5 days. In intact animals testosterone exhibit a rapid increase within hours and a delayed paradoxical increase between 60 and 96 hours. In hypophysectomized animals the first peak is not present. In both intact and hypophysectomized rats hCG receptors are almost undetectable between 10 and 96 hours following hCG injection. Since receptor occupancy cannot account for this phenomenon it is concluded that hCG is exerting a negative control on its own receptors.", "contents": "[Desensitization by human chorionic gonadotropin (hCG): demonstration of a negative control of gonadotropin receptors by hCG at the level of testicular Leydig cells]. A single injection of hCG (500 IU) to intact and hypophysectomized prepubertal rat increases plasma testosterone levels and decreases hCG receptors in the testicular Leydig cells for 4 to 5 days. In intact animals testosterone exhibit a rapid increase within hours and a delayed paradoxical increase between 60 and 96 hours. In hypophysectomized animals the first peak is not present. In both intact and hypophysectomized rats hCG receptors are almost undetectable between 10 and 96 hours following hCG injection. Since receptor occupancy cannot account for this phenomenon it is concluded that hCG is exerting a negative control on its own receptors."}
{"id": "PMID:194724", "title": "[Detection, by direct lymphocyte immunocytotoxicity, of antigens in cells transformed by Rous virus].", "content": "The hamster cells transformed by the Rous Sarcoma Virus (V.S.R.) evidenced surface antigenic alterations that were detected by a method of cellular mediated immunocytotoxicity. Immune hamster lymphocytes were added to tritiated proline prelabeled target cells. These lymphocytes were able to lyse specifically the V.S.R. transformed cells.", "contents": "[Detection, by direct lymphocyte immunocytotoxicity, of antigens in cells transformed by Rous virus]. The hamster cells transformed by the Rous Sarcoma Virus (V.S.R.) evidenced surface antigenic alterations that were detected by a method of cellular mediated immunocytotoxicity. Immune hamster lymphocytes were added to tritiated proline prelabeled target cells. These lymphocytes were able to lyse specifically the V.S.R. transformed cells."}
{"id": "PMID:194725", "title": "[Demonstration of an alpha adrenergic effect on the adipocytes of dog adipose tissue].", "content": "Phentolamine, an alpha blocking agent, potentializes the adrenergical lipolytic effect of isolated fat cells of Canine omental adipose tissue when their average diameter is greater than 80 micrometers. This effect can be found also in isolated fat cells of mesenteric adipose tissue, spontaneously less sensitive with catecholamines. Phenylephrine, alpha sympathomimetic, partially inhibits the lipolytic effect stimulated by isoprenaline.", "contents": "[Demonstration of an alpha adrenergic effect on the adipocytes of dog adipose tissue]. Phentolamine, an alpha blocking agent, potentializes the adrenergical lipolytic effect of isolated fat cells of Canine omental adipose tissue when their average diameter is greater than 80 micrometers. This effect can be found also in isolated fat cells of mesenteric adipose tissue, spontaneously less sensitive with catecholamines. Phenylephrine, alpha sympathomimetic, partially inhibits the lipolytic effect stimulated by isoprenaline."}
{"id": "PMID:194726", "title": "[Induction of endogenous murine C-type viruses. Attempt at discrimination by the pI of polypeptide p30 and the aspect of cellular transformation].", "content": "Endogenous ecotropic and xenotropic murine C-type viruses induced in K-Balb-3T3 cells treated with iododeoxyuridine (IdU) were selected by infection of appropriate indicator cells. The isoelectric point (p1) of the major viral polypeptide (p30) was found to be 6.1 for the ecotropic virus (class I), and 5.7 for the xenotropic virus (class II). An isoelectric form (iso p30) of pl 6.5 was observed in the initial induction peak. In addition, the pattern of cellular alteration in NRK cells at its onset varied according to the pseudotype, the class I pseudotype inducing round cell foci while the foci associated with the class II pseudotype consisted of fusiform cells.", "contents": "[Induction of endogenous murine C-type viruses. Attempt at discrimination by the pI of polypeptide p30 and the aspect of cellular transformation]. Endogenous ecotropic and xenotropic murine C-type viruses induced in K-Balb-3T3 cells treated with iododeoxyuridine (IdU) were selected by infection of appropriate indicator cells. The isoelectric point (p1) of the major viral polypeptide (p30) was found to be 6.1 for the ecotropic virus (class I), and 5.7 for the xenotropic virus (class II). An isoelectric form (iso p30) of pl 6.5 was observed in the initial induction peak. In addition, the pattern of cellular alteration in NRK cells at its onset varied according to the pseudotype, the class I pseudotype inducing round cell foci while the foci associated with the class II pseudotype consisted of fusiform cells."}
{"id": "PMID:194728", "title": "Angiotensin (A I, A II, A III) receptor characterization. Correlation of prostaglandin release with peptide degradation.", "content": "We examined the ability of the angiotensins (A I, A II, A III) to release a prostaglandin E (PGE)-like substance in the isolated Krebs' perfused kidney and mesenteric vasculature of the rabbit by parallel bioassay. In the kidney, the order of potency for PGE release was A II greater than A III greater than A I with ED50's of 36, 100, and 500 pmol, respectively. In the mesenteric preparation, on the other hand, the order of potency was A III greater than A II greater than A I with ED50's of 75, 125, and 500 pmol, respectively. During one transit through the kidney 72-76% of bioassayable A I and A II was degraded. A III was 89% metabolized. In contrast, the mesenteric vasculature inactivated only 27% of A II and 23% of A III. This data suggests an inverse relationship between renal peptide degradation and PGE release. For characterization of the renal angiotensin receptor-mediating PGE release, dissociation constants (KB) of the competitive angiotensin antagonists [IIe7]-A III and [Sar1, IIe3]-A II were determined with each angiotensin. KB values of the individual antaganists were not significantly different with A I, A II, or A III; this finding suggests that one renal angiotensin receptor is involved with PGE release.", "contents": "Angiotensin (A I, A II, A III) receptor characterization. Correlation of prostaglandin release with peptide degradation. We examined the ability of the angiotensins (A I, A II, A III) to release a prostaglandin E (PGE)-like substance in the isolated Krebs' perfused kidney and mesenteric vasculature of the rabbit by parallel bioassay. In the kidney, the order of potency for PGE release was A II greater than A III greater than A I with ED50's of 36, 100, and 500 pmol, respectively. In the mesenteric preparation, on the other hand, the order of potency was A III greater than A II greater than A I with ED50's of 75, 125, and 500 pmol, respectively. During one transit through the kidney 72-76% of bioassayable A I and A II was degraded. A III was 89% metabolized. In contrast, the mesenteric vasculature inactivated only 27% of A II and 23% of A III. This data suggests an inverse relationship between renal peptide degradation and PGE release. For characterization of the renal angiotensin receptor-mediating PGE release, dissociation constants (KB) of the competitive angiotensin antagonists [IIe7]-A III and [Sar1, IIe3]-A II were determined with each angiotensin. KB values of the individual antaganists were not significantly different with A I, A II, or A III; this finding suggests that one renal angiotensin receptor is involved with PGE release."}
{"id": "PMID:194730", "title": "Evaluation of the dual-precipitation method by comparison with the ultracentrifugation method for measurement of lipoproteins in serum.", "content": "We evaluated the dual-precipitation method for quantitative measurement of lipoproteins as described by Wilson and Spiger [J. Lab. Clin. Med. 82, 473 (1973)] for normo- and hyperlipemic sera, by comparison with the results obtained with ultracentrifugation. If serum with an above-normal triglyceride concentration is analyzed, the very-low-density lipoprotein cholesterol value obtained with the precipitation method is usually too low. For measurement of high-density lipoprotein cholesterol the ultracentrifugation and precipitation procedures give comparable results, but the latter method is preferred because sinking pre-beta-lipoproteins present in the high-density lipoprotein fraction isolated by means of the ultracentrifuge may result in falsely high values for cholesterol in that fraction. Therefore, at least for the determination of very-low-density lipoprotein cholesterol in hyperlipemic serum, the use of an ultracentrifuge remains necessary. Because few laboratories have an ultracentrifuge at their disposal, it seemed important to look at the stability of sera in view of the forwarding of samples. Also, a way of increasing the efficiency of the ultracentrifuge was studied. Sera can be stored for a week at 4 degrees C or for 54 h at room temperature without noticeable effect on lipoprotein values. Moreover, reliable values can be obtained with an ultracentrifugation time of 8 h (0.8 X 10(8) g-min).", "contents": "Evaluation of the dual-precipitation method by comparison with the ultracentrifugation method for measurement of lipoproteins in serum. We evaluated the dual-precipitation method for quantitative measurement of lipoproteins as described by Wilson and Spiger [J. Lab. Clin. Med. 82, 473 (1973)] for normo- and hyperlipemic sera, by comparison with the results obtained with ultracentrifugation. If serum with an above-normal triglyceride concentration is analyzed, the very-low-density lipoprotein cholesterol value obtained with the precipitation method is usually too low. For measurement of high-density lipoprotein cholesterol the ultracentrifugation and precipitation procedures give comparable results, but the latter method is preferred because sinking pre-beta-lipoproteins present in the high-density lipoprotein fraction isolated by means of the ultracentrifuge may result in falsely high values for cholesterol in that fraction. Therefore, at least for the determination of very-low-density lipoprotein cholesterol in hyperlipemic serum, the use of an ultracentrifuge remains necessary. Because few laboratories have an ultracentrifuge at their disposal, it seemed important to look at the stability of sera in view of the forwarding of samples. Also, a way of increasing the efficiency of the ultracentrifuge was studied. Sera can be stored for a week at 4 degrees C or for 54 h at room temperature without noticeable effect on lipoprotein values. Moreover, reliable values can be obtained with an ultracentrifugation time of 8 h (0.8 X 10(8) g-min)."}
{"id": "PMID:194731", "title": "Optimal conditions for assaying human lactate dehydrogenase by the lactate-to-pyruvate reaction: Arrhenium relationships for lactate dehydrogenase isoenzymes 1 and 5.", "content": "Optimal reaction conditions to sassay human lactate dehydrogenase (lactate-to-pyruvate) were established for isoenzymes 1 and 5 at 25, 30, and 37 degrees C in diethanolamine and 2-amino-2-methyl-1,3-propanediol. Different substrate concentrations are required at each temperature. The conditions permit measurement of lactate dehydrogenase 1 and 5 with the lowest substrate concentrations that allow for the highest equal sustainable efficiency in measuring both isoenzymes. About 95% of each isoenzyme activity is measured if the assay is performed within the first minute after the reaction is initiated even for activities as high as triple the upper limit of normal. The Arrhenius relationship is different for each isoenzyme, but results obtained for each at one temperature can be compared with results at another temperature by use of simple conversion equations. Assays at 25 and 30 degrees C are more economical and less variable than assays at 37 degrees C.", "contents": "Optimal conditions for assaying human lactate dehydrogenase by the lactate-to-pyruvate reaction: Arrhenium relationships for lactate dehydrogenase isoenzymes 1 and 5. Optimal reaction conditions to sassay human lactate dehydrogenase (lactate-to-pyruvate) were established for isoenzymes 1 and 5 at 25, 30, and 37 degrees C in diethanolamine and 2-amino-2-methyl-1,3-propanediol. Different substrate concentrations are required at each temperature. The conditions permit measurement of lactate dehydrogenase 1 and 5 with the lowest substrate concentrations that allow for the highest equal sustainable efficiency in measuring both isoenzymes. About 95% of each isoenzyme activity is measured if the assay is performed within the first minute after the reaction is initiated even for activities as high as triple the upper limit of normal. The Arrhenius relationship is different for each isoenzyme, but results obtained for each at one temperature can be compared with results at another temperature by use of simple conversion equations. Assays at 25 and 30 degrees C are more economical and less variable than assays at 37 degrees C."}
{"id": "PMID:194732", "title": "Separation of hydroxyproline-containing protein from C1q (a subcomponent of complement) in serum.", "content": "Precipitation of the euglobulin fraction from serum separates C1q from another hydroxyproline-containing protein(s), which remains in the serum-minus-euglobulin fraction. The presence of C1q in the euglobulin fraction has been verified by radial immunodiffusion assay, by sensitivity to collagenase, by hydroxyproline content, and by electrofocusing. The presence of another hydroxyproline-containing protein(s) in the serum-minus-euglobulin fraction has been verified by the same criteria. The isoelectric pH range of C1q is 6.1-7.0; the isoelectric pH range of the other hydroxyproline-containing protein(s) is 4.2-5.5.", "contents": "Separation of hydroxyproline-containing protein from C1q (a subcomponent of complement) in serum. Precipitation of the euglobulin fraction from serum separates C1q from another hydroxyproline-containing protein(s), which remains in the serum-minus-euglobulin fraction. The presence of C1q in the euglobulin fraction has been verified by radial immunodiffusion assay, by sensitivity to collagenase, by hydroxyproline content, and by electrofocusing. The presence of another hydroxyproline-containing protein(s) in the serum-minus-euglobulin fraction has been verified by the same criteria. The isoelectric pH range of C1q is 6.1-7.0; the isoelectric pH range of the other hydroxyproline-containing protein(s) is 4.2-5.5."}
{"id": "PMID:194735", "title": "Enzyme kinetics in single cells: concept and model.", "content": "We describe a technique whereby it is possible to measure enzyme activity in a singel cell. The model chosen involved the measurement of myeloperoxidase activity in a polymorphonuclear neutrophil leukocyte. Details of the apparatus are described. The experiments necessary to optimize the reaction conditions are summarized. The nature of the phases of the reaction are described. The technique appears to have further application in measurement of the activities of other enzymes in leukocytes or other cells.", "contents": "Enzyme kinetics in single cells: concept and model. We describe a technique whereby it is possible to measure enzyme activity in a singel cell. The model chosen involved the measurement of myeloperoxidase activity in a polymorphonuclear neutrophil leukocyte. Details of the apparatus are described. The experiments necessary to optimize the reaction conditions are summarized. The nature of the phases of the reaction are described. The technique appears to have further application in measurement of the activities of other enzymes in leukocytes or other cells."}
{"id": "PMID:194737", "title": "Studies on the pre-alpha-lipoprotein in patients with familial lecithin: cholesterol acyltransferase deficiency.", "content": "The present study shows that regular alpha1- and pre-alpha-lipoproteins cannot be detected in serum of patients with familial lecithin: cholesterol acyltransferase (LCAT) deficiency. After electrophoresis on agarose gel only one single band of albumin mobility was observed in the alpha1-pre-alpha-region. In contrast to sera of normal subjects neither the anodic front nor the cathodic part of this region revealed any lipoprotein bands in the patients studied. The lack of the cathodic part might be related to a low amount of alpha1-lipoprotein. The apparent lack of the anodic front could be related to a low amount of \"albumin-Apo-A-I-containing lipoprotein\" (AAL). AAL was not detected with conventional methods in LCAT deficient sera. The alpha1-lipoprotein was made up of two immunologically identical peaks, both of which had a Sudanophilic character. After incubation of lysolecithin with albumin and AAL and subsequent thin layer chromatography, a significant lysolecithin-binding capacity of AAL was demonstrated, superior to that possessed by albumin.", "contents": "Studies on the pre-alpha-lipoprotein in patients with familial lecithin: cholesterol acyltransferase deficiency. The present study shows that regular alpha1- and pre-alpha-lipoproteins cannot be detected in serum of patients with familial lecithin: cholesterol acyltransferase (LCAT) deficiency. After electrophoresis on agarose gel only one single band of albumin mobility was observed in the alpha1-pre-alpha-region. In contrast to sera of normal subjects neither the anodic front nor the cathodic part of this region revealed any lipoprotein bands in the patients studied. The lack of the cathodic part might be related to a low amount of alpha1-lipoprotein. The apparent lack of the anodic front could be related to a low amount of \"albumin-Apo-A-I-containing lipoprotein\" (AAL). AAL was not detected with conventional methods in LCAT deficient sera. The alpha1-lipoprotein was made up of two immunologically identical peaks, both of which had a Sudanophilic character. After incubation of lysolecithin with albumin and AAL and subsequent thin layer chromatography, a significant lysolecithin-binding capacity of AAL was demonstrated, superior to that possessed by albumin."}
{"id": "PMID:194743", "title": "Radiotheraphy in chemodectoma of the glomus jugulare.", "content": "Twenty-five patients treated for glomus jugulare tumours over a 13-year period are reviewed, the majority (20) receiving radiotherapy only. Only two patients developed tumour recurrence, one following inadequate-dose radiotherapy, the other after surgery. Both are doing well following radiotherapy for their recurrent disease. Two patients were lost to follow-up and five have died of unrelated disease, four with no tumour reactivation over a prolonged period. The remaining 16 patients have been maintained in continuous tumour control for periods ranging from 4 to 15 years. While these tumours are by nature slow growing and usually not malignant, they demand radical treatment due to the symptomatology they create. Radiotherapy would seem to offer excellent prospect of satisfactory tumour control.", "contents": "Radiotheraphy in chemodectoma of the glomus jugulare. Twenty-five patients treated for glomus jugulare tumours over a 13-year period are reviewed, the majority (20) receiving radiotherapy only. Only two patients developed tumour recurrence, one following inadequate-dose radiotherapy, the other after surgery. Both are doing well following radiotherapy for their recurrent disease. Two patients were lost to follow-up and five have died of unrelated disease, four with no tumour reactivation over a prolonged period. The remaining 16 patients have been maintained in continuous tumour control for periods ranging from 4 to 15 years. While these tumours are by nature slow growing and usually not malignant, they demand radical treatment due to the symptomatology they create. Radiotherapy would seem to offer excellent prospect of satisfactory tumour control."}
{"id": "PMID:194757", "title": "Endodermal sinus tumor of the mediastinum. Ultrastructural study.", "content": "This is the eighth case report of an endodermal sinus tumor of the mediastinum (first case studied by electron microscopy). The ultrastructure of the tumor was found to mimic that of the normal yolk sac and was also similar to that of three previously reported cases of endodermal sinus tumor of the ovary, thus confirming the correctness of Teilum's original interpretation of the tumor as arising in germ cells and differentiating towards extraembryonic structures.", "contents": "Endodermal sinus tumor of the mediastinum. Ultrastructural study. This is the eighth case report of an endodermal sinus tumor of the mediastinum (first case studied by electron microscopy). The ultrastructure of the tumor was found to mimic that of the normal yolk sac and was also similar to that of three previously reported cases of endodermal sinus tumor of the ovary, thus confirming the correctness of Teilum's original interpretation of the tumor as arising in germ cells and differentiating towards extraembryonic structures."}
{"id": "PMID:194762", "title": "[Tryptic pancreatitis in small-cell bronchial carcinoma (author's transl)].", "content": "In two cases of typical small-cell bronchial carcinoma (one of them peripheral, small and clinically not diagnosed) destructive parenchylmal metastases in the pancreas, carcinomatous lymphoangiosis and infiltration of the larger excretory ducts by tumour cells were demonstrated. In both the clinical course was dominated by tryptic pancreatitis with treatment-refractory hypokalaemia. Since pancreatic metastases occur in about 10% of bronchial carcinomas, tryptic pancreatitis is, however, only rarely observed. It is, therefore, likely that autodigestion occurs only if in addition to parenchymal destruction by the metastases there are other factors. These may be blockage of lymphatic flow by carcinomatous lymphangiosis and duct stenosis by tumour infiltration of the walls. Hypercorticism due to ectopic ACTH production by the small-cell carcinoma may also be factor, but is without proof.", "contents": "[Tryptic pancreatitis in small-cell bronchial carcinoma (author's transl)]. In two cases of typical small-cell bronchial carcinoma (one of them peripheral, small and clinically not diagnosed) destructive parenchylmal metastases in the pancreas, carcinomatous lymphoangiosis and infiltration of the larger excretory ducts by tumour cells were demonstrated. In both the clinical course was dominated by tryptic pancreatitis with treatment-refractory hypokalaemia. Since pancreatic metastases occur in about 10% of bronchial carcinomas, tryptic pancreatitis is, however, only rarely observed. It is, therefore, likely that autodigestion occurs only if in addition to parenchymal destruction by the metastases there are other factors. These may be blockage of lymphatic flow by carcinomatous lymphangiosis and duct stenosis by tumour infiltration of the walls. Hypercorticism due to ectopic ACTH production by the small-cell carcinoma may also be factor, but is without proof."}
{"id": "PMID:194759", "title": "Extramammary perianal Paget's disease: report of a case.", "content": "The case report of a patient with extramammary perianal Paget's disease who developed three histologic types of adenocarcinoma of the rectum over a period of six years is described.", "contents": "Extramammary perianal Paget's disease: report of a case. The case report of a patient with extramammary perianal Paget's disease who developed three histologic types of adenocarcinoma of the rectum over a period of six years is described."}
{"id": "PMID:194769", "title": "A radioreceptor assay for insulin: direct measurement of dog pancreatic vein serum insulin.", "content": "A simple radioreceptor assay for insulin rat liver membranes as receptor sites, with sufficient specificity precision, and sensitivity to detect 10 ng or 276 muU/ml of serum insulin, has been developed. In the presence of standard porcine insulin at the concentration of 1.0 ng/tube, approximately 8% of 125I-porcine insulin was bound to the plasma membranes and ninety-five per cent of this binding was inhibited by 1.0 microgram of standard insulin per tube. Four animal insulins inhibited the binding of 125I-insulin while ACTH, glucagon, human growth hormone, and oxytocin were inert. Insulin values in dog pancreatic vein sera obtained during and after glucose loading and measured by the present radioreceptor assay agreed well with immunoreactive insulin. The ratio of IRI to the measurement by radioreceptor assay was 1.09 +/- 0.18 for the same sera.", "contents": "A radioreceptor assay for insulin: direct measurement of dog pancreatic vein serum insulin. A simple radioreceptor assay for insulin rat liver membranes as receptor sites, with sufficient specificity precision, and sensitivity to detect 10 ng or 276 muU/ml of serum insulin, has been developed. In the presence of standard porcine insulin at the concentration of 1.0 ng/tube, approximately 8% of 125I-porcine insulin was bound to the plasma membranes and ninety-five per cent of this binding was inhibited by 1.0 microgram of standard insulin per tube. Four animal insulins inhibited the binding of 125I-insulin while ACTH, glucagon, human growth hormone, and oxytocin were inert. Insulin values in dog pancreatic vein sera obtained during and after glucose loading and measured by the present radioreceptor assay agreed well with immunoreactive insulin. The ratio of IRI to the measurement by radioreceptor assay was 1.09 +/- 0.18 for the same sera."}
{"id": "PMID:194770", "title": "Effect of 1alphaOH-vitamin D3 in a case of pseudohypoparathyroidism.", "content": "A 37-year-old woman with typical features of pseudohypoparathyroidism (chronic tetany, paresthesia, persistent hypocalcemia, round face, short stature, short metacarpals and metatarsals, cucutaneous calcification and lack of response to exogenous and endogenous parathyroid hormone as regards urinary phosphate and cyclic AMP excretion) was treated with oral administration of 2 microgram/day of 1alphaOH-vitamin D3. Serum calcium started to rise within 3 days returning to the normal level with disappearance of symptoms referrable to hypocalcemia. Such a favorable effect of a small dose of 1alphaOH-vitamin D3 in a patient with typical hypoparathyroidism suggests an important role of disturbance of 1alpha-hydroxylation of vitamin D3 by the kidney in the pathogenesis of calcium and phosphorus abnormality in this disease. Forty-four cases of pseudohypoparathyroidism in the Japanese literature were briefly reviewed.", "contents": "Effect of 1alphaOH-vitamin D3 in a case of pseudohypoparathyroidism. A 37-year-old woman with typical features of pseudohypoparathyroidism (chronic tetany, paresthesia, persistent hypocalcemia, round face, short stature, short metacarpals and metatarsals, cucutaneous calcification and lack of response to exogenous and endogenous parathyroid hormone as regards urinary phosphate and cyclic AMP excretion) was treated with oral administration of 2 microgram/day of 1alphaOH-vitamin D3. Serum calcium started to rise within 3 days returning to the normal level with disappearance of symptoms referrable to hypocalcemia. Such a favorable effect of a small dose of 1alphaOH-vitamin D3 in a patient with typical hypoparathyroidism suggests an important role of disturbance of 1alpha-hydroxylation of vitamin D3 by the kidney in the pathogenesis of calcium and phosphorus abnormality in this disease. Forty-four cases of pseudohypoparathyroidism in the Japanese literature were briefly reviewed."}
{"id": "PMID:194771", "title": "Cyclic AMP accumulation in cerebral cortical slices: effect of carbamazepine, phenobarbital, and phenytoin.", "content": "Recent investigations have suggested that abnormal increases in brain cyclic 3',5'-adenosine monophosphate (cAMP) may play a role in epileptogenesis. Therefore, the effect of three commonly used antiepileptic drugs on cAMP accumulation in rat cortex slices was investigated. Ouabain, a depolarizing agent which produces seizures when applied to rat cortex, produced a five- to sevenfold increase in cAMP accumulation, and both carbamazepine and and phenytoin inhibited this increase. Ouabain stimulation may be mediated by the release of endogenous adenosine, and carbamazepine antagonized adenosine stimulation of cAMP accumulation whereas phenytoin did not. Carbamazepine had no effect on adenosine efflux. The augmentation of cAMP accumulation by norepinephrine was inhibited by carbamazepine and phenobarbital but slightly increased by phenytoin. If increases in brain cAMP are involved in epileptogenesis, the antagonism of cAMP accumulation by antiepileptic drugs may play a role in their anticonvulsant action.", "contents": "Cyclic AMP accumulation in cerebral cortical slices: effect of carbamazepine, phenobarbital, and phenytoin. Recent investigations have suggested that abnormal increases in brain cyclic 3',5'-adenosine monophosphate (cAMP) may play a role in epileptogenesis. Therefore, the effect of three commonly used antiepileptic drugs on cAMP accumulation in rat cortex slices was investigated. Ouabain, a depolarizing agent which produces seizures when applied to rat cortex, produced a five- to sevenfold increase in cAMP accumulation, and both carbamazepine and and phenytoin inhibited this increase. Ouabain stimulation may be mediated by the release of endogenous adenosine, and carbamazepine antagonized adenosine stimulation of cAMP accumulation whereas phenytoin did not. Carbamazepine had no effect on adenosine efflux. The augmentation of cAMP accumulation by norepinephrine was inhibited by carbamazepine and phenobarbital but slightly increased by phenytoin. If increases in brain cAMP are involved in epileptogenesis, the antagonism of cAMP accumulation by antiepileptic drugs may play a role in their anticonvulsant action."}
{"id": "PMID:194772", "title": "Effect of carbamazepine on the in vitro uptake and release of norepinephrine in adrenergic nerves of rabbit aorta and in whole brain synaptosomes.", "content": "The effects of carbamazepine, in vitro, on adrenergic neuronal and whole brain synaptosomal uptake and release of tritiated norepinephrine (3H-NE) were assessed. At 10(-4) M, carbamazepine inhibited 3H-NE uptake by 22% in rabbit thoracic aorta and in brain synaptosomes. At the same concentration, carbamazepine inhibited stimulation-induced release of 3H-NE by 42.6% and inhibited isometric contraction in rabbit ear artery helical strips by 31.6%. At 10(-5) M, carbamazepine exhibited a 17.6% inhibition of 3H-NE uptake in brain synaptosomes in the absence of effects on transmitter release. Cocaine, 10(-4) M, and imipramine, 10(-4) M, inhibited uptake by 88% and 85%, respectively, in aorta, and cocaine, 10(-4) M, inhibited synaptosomal uptake by 67.7%. Since antiepileptic blood levels of carbamazepine range between 1.3 and 3.0 X 10(-5) M, it was concluded that the observed effects of carbamazepine are insufficient to account for the anticonvulsant action of the drug. However, the blockade of 3H-NE uptake by brain synaptosomes at 10(-5) M serves to explain the recently described analeptic activity of this agent.", "contents": "Effect of carbamazepine on the in vitro uptake and release of norepinephrine in adrenergic nerves of rabbit aorta and in whole brain synaptosomes. The effects of carbamazepine, in vitro, on adrenergic neuronal and whole brain synaptosomal uptake and release of tritiated norepinephrine (3H-NE) were assessed. At 10(-4) M, carbamazepine inhibited 3H-NE uptake by 22% in rabbit thoracic aorta and in brain synaptosomes. At the same concentration, carbamazepine inhibited stimulation-induced release of 3H-NE by 42.6% and inhibited isometric contraction in rabbit ear artery helical strips by 31.6%. At 10(-5) M, carbamazepine exhibited a 17.6% inhibition of 3H-NE uptake in brain synaptosomes in the absence of effects on transmitter release. Cocaine, 10(-4) M, and imipramine, 10(-4) M, inhibited uptake by 88% and 85%, respectively, in aorta, and cocaine, 10(-4) M, inhibited synaptosomal uptake by 67.7%. Since antiepileptic blood levels of carbamazepine range between 1.3 and 3.0 X 10(-5) M, it was concluded that the observed effects of carbamazepine are insufficient to account for the anticonvulsant action of the drug. However, the blockade of 3H-NE uptake by brain synaptosomes at 10(-5) M serves to explain the recently described analeptic activity of this agent."}
{"id": "PMID:194773", "title": "Acrodermatitis enteropathica. II. Zinc deficiency and ultrastructural findings.", "content": "The basic defect in acrodermatitis enteropathica (A.E.) is zinc deficiency caused by zinc malabsorption. The clinical symptoms disappear and serum zinc levels normalize after oral treatment with zinc. A report is given on two siblings suffering from A.E., both treated with oxyquinolines for a long period with changing clinical success. A permanent clinical remission could be achieved by treatment with zinc-sulphate at doses of 110-220 mg daily. The serum zinc levels normalized. The correlation between the zinc concentration of the hair and the kind of therapy was not very close. As we have shown in our first communication, the Paneth cells of the intestinal mucosa display ultrastructural changes in form of an unhomogeneous structure of the cytoplasm, formation of giant granules, and inclusion bodies. The zinc-therapy led to a complete normalization of the pathological changes in the Paneth cells. Thus, the changes in the Paneth cells in A.E. are the result and not the cause of zinc deficiency.", "contents": "Acrodermatitis enteropathica. II. Zinc deficiency and ultrastructural findings. The basic defect in acrodermatitis enteropathica (A.E.) is zinc deficiency caused by zinc malabsorption. The clinical symptoms disappear and serum zinc levels normalize after oral treatment with zinc. A report is given on two siblings suffering from A.E., both treated with oxyquinolines for a long period with changing clinical success. A permanent clinical remission could be achieved by treatment with zinc-sulphate at doses of 110-220 mg daily. The serum zinc levels normalized. The correlation between the zinc concentration of the hair and the kind of therapy was not very close. As we have shown in our first communication, the Paneth cells of the intestinal mucosa display ultrastructural changes in form of an unhomogeneous structure of the cytoplasm, formation of giant granules, and inclusion bodies. The zinc-therapy led to a complete normalization of the pathological changes in the Paneth cells. Thus, the changes in the Paneth cells in A.E. are the result and not the cause of zinc deficiency."}
{"id": "PMID:194774", "title": "Prognosis in carcinoma of the urachus.", "content": "The literature regarding the prognosis of carcinoma of the urachus is reviewed. Factors affecting the prognosis are discussed. En bloc partial cystectomy, if feasible, is the form of treatment which gives the best long-term survival rate. A series of 5 cases is presented with a 13-year survival rate of 40%.", "contents": "Prognosis in carcinoma of the urachus. The literature regarding the prognosis of carcinoma of the urachus is reviewed. Factors affecting the prognosis are discussed. En bloc partial cystectomy, if feasible, is the form of treatment which gives the best long-term survival rate. A series of 5 cases is presented with a 13-year survival rate of 40%."}
{"id": "PMID:194775", "title": "Age changes in the neuromuscular system of rats.", "content": "Data relating to the effects of aging on the neuromuscular system of rats have been reviewed and summarized. Age effects of muscle, nerve and neuromuscular junction are presented only in a descriptive, qualitative manner, primarily due to paucity of well controlled experimentation in this area. Certain morphological and biochemical changes taking place with aging of the neuromuscular system are discussed, but no conclusive hypotheses can be presented at this time explaining diminution of motor activity in old animals.", "contents": "Age changes in the neuromuscular system of rats. Data relating to the effects of aging on the neuromuscular system of rats have been reviewed and summarized. Age effects of muscle, nerve and neuromuscular junction are presented only in a descriptive, qualitative manner, primarily due to paucity of well controlled experimentation in this area. Certain morphological and biochemical changes taking place with aging of the neuromuscular system are discussed, but no conclusive hypotheses can be presented at this time explaining diminution of motor activity in old animals."}
{"id": "PMID:194781", "title": "Differentiation of opiate and neuroleptic receptor binding in rat brain.", "content": "For 6 large series of compounds derived from the piperidine moieties of spiperone, pimozide, haloperidol, pethidine, fentanyl and 4-methocarboxy-fentanyl, IC50 values were determined in the opiate and neuroleptic binding assay using [3H]-fentanyl and [3H]-haloperidol as ligands, respectively. The specificity and difference between both receptors were demonstrated on the basis of several criteria (1) the sterospecificity of the binding (2) the significant correlation between the in vitro activity of the drugs and their pharmacological potency in vivo, not withstanding some discrepancies which are probably of pharmacokinetic and/or metabolic origin (3) the ability to discriminate between morphinomimetic and neuroleptic drugs by the differential affinity for their specific receptro (4) the structure--activity relationships derived from the in vitro data indicating that the structural requirements for high affinity binding in vitro parallel those for high in vivo potency (5) a demonstration, on the basis of physicochemical principles, of the difference in binding mechanism between morphinomimetics and neuroleptics to their respective receptor.", "contents": "Differentiation of opiate and neuroleptic receptor binding in rat brain. For 6 large series of compounds derived from the piperidine moieties of spiperone, pimozide, haloperidol, pethidine, fentanyl and 4-methocarboxy-fentanyl, IC50 values were determined in the opiate and neuroleptic binding assay using [3H]-fentanyl and [3H]-haloperidol as ligands, respectively. The specificity and difference between both receptors were demonstrated on the basis of several criteria (1) the sterospecificity of the binding (2) the significant correlation between the in vitro activity of the drugs and their pharmacological potency in vivo, not withstanding some discrepancies which are probably of pharmacokinetic and/or metabolic origin (3) the ability to discriminate between morphinomimetic and neuroleptic drugs by the differential affinity for their specific receptro (4) the structure--activity relationships derived from the in vitro data indicating that the structural requirements for high affinity binding in vitro parallel those for high in vivo potency (5) a demonstration, on the basis of physicochemical principles, of the difference in binding mechanism between morphinomimetics and neuroleptics to their respective receptor."}
{"id": "PMID:194787", "title": "[Effect of insulin, adrenaline and cyclic adenosine monophosphate on the activity of transport adenosine triphosphatases and pyruvate dehydrogenase of the rat myocardium under normal conditions and in insular insufficiency].", "content": "Experiments with rats were set up to study the interaction of hormones with Na+, K+-ATP-ase and Ca2+-ATP-ase of the sarcoplasmatic reticulum fragments and with pyruvate-dehydrogenase of the myocardial mitochondria in healthy rats and the ones with alloxan diabetes. Insulin was found to activate, while epinephrine and c-AMP to inhibit Na+, K+-ATP-ase. The Ca2+-ATP-ase is activated with epinephrine and c-AMP. In alloxan diabetes Na+, K+-ATP-ase is inhibited and Ca2+-ATP-ase and pyruvate-dehydrogenase--activated.", "contents": "[Effect of insulin, adrenaline and cyclic adenosine monophosphate on the activity of transport adenosine triphosphatases and pyruvate dehydrogenase of the rat myocardium under normal conditions and in insular insufficiency]. Experiments with rats were set up to study the interaction of hormones with Na+, K+-ATP-ase and Ca2+-ATP-ase of the sarcoplasmatic reticulum fragments and with pyruvate-dehydrogenase of the myocardial mitochondria in healthy rats and the ones with alloxan diabetes. Insulin was found to activate, while epinephrine and c-AMP to inhibit Na+, K+-ATP-ase. The Ca2+-ATP-ase is activated with epinephrine and c-AMP. In alloxan diabetes Na+, K+-ATP-ase is inhibited and Ca2+-ATP-ase and pyruvate-dehydrogenase--activated."}
{"id": "PMID:194788", "title": "[Effect of diethylene-triaminopentamethylphosphonic acid complex on various hematologic and biochemical indicators in experimental animals].", "content": "A successive triple introduction of organophosphorus complexon DTPP (sodium-dicalcium salt of diethylene-triaminopentamethylphosphonic acid) in a dose of 500 mg/kg to albino male rats did not produce any marked effect on the composition of the peripheral blood. Some shortening of the initial period in blood coagulation process was noted. DTPP produced a moderate stimulation of the iron-containing enzymes (catalase, peroxidase, cytochroxidase) which led to an increased oxygen consumption. The blood serum and urine potassium, sodium and calcium content did not undergo any significant changes, while the magnesium concentration in the blood serum dropped by 37 pc and in the urine rose by as much as twice as compared to controls. This bears evidence to an elevated discharge of magnesium from the organism following the action of the DTPP complexon.", "contents": "[Effect of diethylene-triaminopentamethylphosphonic acid complex on various hematologic and biochemical indicators in experimental animals]. A successive triple introduction of organophosphorus complexon DTPP (sodium-dicalcium salt of diethylene-triaminopentamethylphosphonic acid) in a dose of 500 mg/kg to albino male rats did not produce any marked effect on the composition of the peripheral blood. Some shortening of the initial period in blood coagulation process was noted. DTPP produced a moderate stimulation of the iron-containing enzymes (catalase, peroxidase, cytochroxidase) which led to an increased oxygen consumption. The blood serum and urine potassium, sodium and calcium content did not undergo any significant changes, while the magnesium concentration in the blood serum dropped by 37 pc and in the urine rose by as much as twice as compared to controls. This bears evidence to an elevated discharge of magnesium from the organism following the action of the DTPP complexon."}
{"id": "PMID:194789", "title": "[Effectiveness of combination of various antihypoxic drugs in acute hypoxic hypoxia].", "content": "In experiments with mice evidence was obtained that a combination of apressin with obsidan and diprazine; of adenosine with nicotinamide-adenine-dinucleotide (NAD) and also a mixture of both combinations produce a marked protective effect in hypo and normobaric hypoxic hypoxia.", "contents": "[Effectiveness of combination of various antihypoxic drugs in acute hypoxic hypoxia]. In experiments with mice evidence was obtained that a combination of apressin with obsidan and diprazine; of adenosine with nicotinamide-adenine-dinucleotide (NAD) and also a mixture of both combinations produce a marked protective effect in hypo and normobaric hypoxic hypoxia."}
{"id": "PMID:194790", "title": "[Effect of cytostatic drugs, administered against the background of the action of insulin and thyroxine, on the processes of glycolysis and biosynthetic processes of neoplastic cells].", "content": "Experiments conducted on albino rats with a grafted tumour of transplantable alveolar mucinous carcinoma PC evidence that the cytostatic effect of thiophosphamide and sarcolysin equally grows in strenght with simultaneous introduction of thyroxin or insulin into the organism. In the same conditions the antineoplastic action of phthorafur is in a greater measure determined by the level of insulin and to a lesser degree by that of thyroxin. An analysis of the results subsequent to a biochemical examination (determination of the pyruvate, lactate, thiamine concentration in the blood and in the tumour, the rate of the 14C-glyxine incorporation in the protein of cancer cells) bears proof to the fact the neoplasm continues to definetly react in response to exogenously introduced hormones, this bringing changes into the kinetic and dynamic properties of the cytostatics.", "contents": "[Effect of cytostatic drugs, administered against the background of the action of insulin and thyroxine, on the processes of glycolysis and biosynthetic processes of neoplastic cells]. Experiments conducted on albino rats with a grafted tumour of transplantable alveolar mucinous carcinoma PC evidence that the cytostatic effect of thiophosphamide and sarcolysin equally grows in strenght with simultaneous introduction of thyroxin or insulin into the organism. In the same conditions the antineoplastic action of phthorafur is in a greater measure determined by the level of insulin and to a lesser degree by that of thyroxin. An analysis of the results subsequent to a biochemical examination (determination of the pyruvate, lactate, thiamine concentration in the blood and in the tumour, the rate of the 14C-glyxine incorporation in the protein of cancer cells) bears proof to the fact the neoplasm continues to definetly react in response to exogenously introduced hormones, this bringing changes into the kinetic and dynamic properties of the cytostatics."}
{"id": "PMID:194798", "title": "General thermodynamic considerations of receptor interactions.", "content": "Assuming that the biological response is directly proportional to the fractional degree of receptor occupancy, the mathematical relationships between free ligand concentration, receptor occupation and biological activity are developed for a number of equilibrium models. The models considered include simple 1:1 binding with and without conformational changes in the receptor, the coupled binding of two distinct effectors to a single macromolecule, and a system involving indirect coupling between two effectors that bind to two distinct components of the receptor system. This latter model is elaborated into the concept of a domain of receptor-enzyme pairs such that occupation of a single receptor may activate the entire domain of enzymes. This model can explain discrepancies between activation and binding isotherms as has been found with some beta-adrenergic agonist-sensitive adenylate cyclase systems.", "contents": "General thermodynamic considerations of receptor interactions. Assuming that the biological response is directly proportional to the fractional degree of receptor occupancy, the mathematical relationships between free ligand concentration, receptor occupation and biological activity are developed for a number of equilibrium models. The models considered include simple 1:1 binding with and without conformational changes in the receptor, the coupled binding of two distinct effectors to a single macromolecule, and a system involving indirect coupling between two effectors that bind to two distinct components of the receptor system. This latter model is elaborated into the concept of a domain of receptor-enzyme pairs such that occupation of a single receptor may activate the entire domain of enzymes. This model can explain discrepancies between activation and binding isotherms as has been found with some beta-adrenergic agonist-sensitive adenylate cyclase systems."}
{"id": "PMID:194800", "title": "Mechanisms and sites of action of newer angiotensin agonists and antagonists in terms of activity and receptor.", "content": "From the myotropic and vasopressor activities of the numerous analogs of angiotensin II, it has been determined that the phenyl group of position 8 possesses the information for biologic response while the aromatic side groups in positions 4 and 6, the guanido group in position 2 and the C-terminal carboxyl are involved in binding to the receptor site. Removal of a side group of the C-terminal phenyalanine yields peptides that bind to the receptor. While many of these have low agonist properties, all have antagonist properties. Modifications in the aromatic side groups affect conformation of the octapeptide. This change may relate to receptor binding but sufficient data are not yet available to determine a correlation pattern. A proposed conformation for angiotensin is given as well as an artist's concept of angiotensin II binding to its membrane receptor utilizing the groups known to be involved in binding. Both angiotensin II and III [des-Asp] angiotensin II stimulate the biosynthesis and release of aldosterone from adrenal glomerulosa cells. Sufficient data are not yet available to determine whether the conversion of angiotensin II to angiotensin III is neccessary for the steroidogenesis activity.", "contents": "Mechanisms and sites of action of newer angiotensin agonists and antagonists in terms of activity and receptor. From the myotropic and vasopressor activities of the numerous analogs of angiotensin II, it has been determined that the phenyl group of position 8 possesses the information for biologic response while the aromatic side groups in positions 4 and 6, the guanido group in position 2 and the C-terminal carboxyl are involved in binding to the receptor site. Removal of a side group of the C-terminal phenyalanine yields peptides that bind to the receptor. While many of these have low agonist properties, all have antagonist properties. Modifications in the aromatic side groups affect conformation of the octapeptide. This change may relate to receptor binding but sufficient data are not yet available to determine a correlation pattern. A proposed conformation for angiotensin is given as well as an artist's concept of angiotensin II binding to its membrane receptor utilizing the groups known to be involved in binding. Both angiotensin II and III [des-Asp] angiotensin II stimulate the biosynthesis and release of aldosterone from adrenal glomerulosa cells. Sufficient data are not yet available to determine whether the conversion of angiotensin II to angiotensin III is neccessary for the steroidogenesis activity."}
{"id": "PMID:194801", "title": "[Effect of natural exogenous estrogens on the response to LH-RH (author's transl)].", "content": "LH-RH in doses of 25 and 50 microgram,, was injected intravenously into normal women pre-treated or not with conjugated natural estrogen. An inhibition of the  release of LH in response to 25 as well as 50 microgram of LH-RH, was observed in women receiving either dose of estrogens (0.628 and 1.25 mg).", "contents": "[Effect of natural exogenous estrogens on the response to LH-RH (author's transl)]. LH-RH in doses of 25 and 50 microgram,, was injected intravenously into normal women pre-treated or not with conjugated natural estrogen. An inhibition of the  release of LH in response to 25 as well as 50 microgram of LH-RH, was observed in women receiving either dose of estrogens (0.628 and 1.25 mg)."}
{"id": "PMID:194808", "title": "Nesidioblastosis: the pathologic basis of persistent hyperinsulinemic hypoglycemia in infants. Morphologic and quantitative analysis of seven cases based on specific immunostaining and electron microscopy.", "content": "Seven surgical specimens of pancreas, obtained at laparotomy from infants suffering from persistent hyperinsulinemic hypoglycemia, were analyzed by qualitative and quantitative immunocytochemistry and by electron microscopy. In five cases a multifocal ductuloinsular proliferation, in one a focal adenomatosis, and in one a solitary encapsulated nodule (adenoma) were observed. Combinations of the different patterns of proliferation were seen in six cases. Budding off from the ductular epithelium and interposition of endocrine cells between ductular epithelial cells were prominent features common to all cases. An almost fivefold increase of the mean total area occupied by endocrine tissue was found over that of age-matched controls. Four cell types were seen to participate regularly in the proliferation, and their ratios were remarkably constant in all cases, mean figures being 62:21:9:8% for B:A:D:D1 cells, respectively. The ratio of B cells per total endocrine area in nesidioblastosis was very close to that per islet of the controls (62:59%). Since common features were found in all or in the majority of cases, it is suggested that the various patterns of proliferation are merely morphologic variations of the same basic defect. Nesidioblastosis may result from inappropriately controlled development of the endocrine pancreas that is not arrested but carries on beyond birth and during infancy. The application of specific immunocytochemistry as a necessity for full appreciation of the extent of endocrine proliferation is stressed.", "contents": "Nesidioblastosis: the pathologic basis of persistent hyperinsulinemic hypoglycemia in infants. Morphologic and quantitative analysis of seven cases based on specific immunostaining and electron microscopy. Seven surgical specimens of pancreas, obtained at laparotomy from infants suffering from persistent hyperinsulinemic hypoglycemia, were analyzed by qualitative and quantitative immunocytochemistry and by electron microscopy. In five cases a multifocal ductuloinsular proliferation, in one a focal adenomatosis, and in one a solitary encapsulated nodule (adenoma) were observed. Combinations of the different patterns of proliferation were seen in six cases. Budding off from the ductular epithelium and interposition of endocrine cells between ductular epithelial cells were prominent features common to all cases. An almost fivefold increase of the mean total area occupied by endocrine tissue was found over that of age-matched controls. Four cell types were seen to participate regularly in the proliferation, and their ratios were remarkably constant in all cases, mean figures being 62:21:9:8% for B:A:D:D1 cells, respectively. The ratio of B cells per total endocrine area in nesidioblastosis was very close to that per islet of the controls (62:59%). Since common features were found in all or in the majority of cases, it is suggested that the various patterns of proliferation are merely morphologic variations of the same basic defect. Nesidioblastosis may result from inappropriately controlled development of the endocrine pancreas that is not arrested but carries on beyond birth and during infancy. The application of specific immunocytochemistry as a necessity for full appreciation of the extent of endocrine proliferation is stressed."}
{"id": "PMID:194809", "title": "In-vitro observations on isolated adipose tissue cells from hyperobese subjects.", "content": "Isolated adipose tissue cells were prepared from subcutaneous samples obtained from nine morbidly obese subjects weighing from 187 to 306% of ideal body weight. The responsiveness of these adipocytes to a number of test substances was determined by measuring cellular cyclic AMP concentration at one-half hour and glycerol release at four hours. Theophylline (10(-3) M) and epinephrine (10(-5) M) stimulated lipolysis; theophylline stimulated an increase in cyclic AMP, while epinephrine failed to prompt a significant change in the nucleotide. Neither the alpha blocker, phentolamine (10(-5) M), nor the beta blocker, propranolol (3 X 10(-5) M), affected lipolysis or cyclic AMP; when these agents were incubated in combination with epinephrine, changes occurred indicative of the presence of both alpha and beta adrenergic receptor sites. Insulin significantly reduced both basal and stimulated lipolysis but failed to affect cyclic AMP. With minor exceptions, adipocytes from hyperobese subjects behaved similarly to cells from unselected donors; at the concentration used, there was no evidence of resistance to insulin.", "contents": "In-vitro observations on isolated adipose tissue cells from hyperobese subjects. Isolated adipose tissue cells were prepared from subcutaneous samples obtained from nine morbidly obese subjects weighing from 187 to 306% of ideal body weight. The responsiveness of these adipocytes to a number of test substances was determined by measuring cellular cyclic AMP concentration at one-half hour and glycerol release at four hours. Theophylline (10(-3) M) and epinephrine (10(-5) M) stimulated lipolysis; theophylline stimulated an increase in cyclic AMP, while epinephrine failed to prompt a significant change in the nucleotide. Neither the alpha blocker, phentolamine (10(-5) M), nor the beta blocker, propranolol (3 X 10(-5) M), affected lipolysis or cyclic AMP; when these agents were incubated in combination with epinephrine, changes occurred indicative of the presence of both alpha and beta adrenergic receptor sites. Insulin significantly reduced both basal and stimulated lipolysis but failed to affect cyclic AMP. With minor exceptions, adipocytes from hyperobese subjects behaved similarly to cells from unselected donors; at the concentration used, there was no evidence of resistance to insulin."}
{"id": "PMID:194821", "title": "[The Landry-Guillain-Barr\u00e9-Strohl-syndrome. Prognosis in adults (author's transl)].", "content": "The clinical aspect of acute polyradiculitis (Landry-Guillain-Barr\u00e9-Strohl syndrome) of 85 patients is resumed. 52 of these 85 patients were seen after an average of 5, 1 years, 8 were dead at the time of control and 25 could not be traced. Two patients died during the acute phase of polyradiculitis corresponding to a letality of 2%. 24 of the subjects (46%) had recovered completely, 28 (54%) showed some residual symptoms. Eleven patients (21%) had some residual weakness of hands and/or feet. Out of these eleven six (11% of total) were so much disabled that they received a disablement pension. 17 patients with slight sensory disturbances and/or some loss of reflexes were not handicapped in their every-day life. 20 patients were examined electrophysiologically during the follow-up. All the five patients with a pathological EMG also showed some clinical residual signs. A positive correlation between pathological conduction velocities in the median and/or deep peroneal nerve and clinical residua was only inconstantly found. Patients with severe tetraparesis during the acute phase had more often residual symptoms. The time from the maximum motor deficiency to the beginning of recovery was longer in the latter group than in patients without residual symptoms (23 respectively 8 days) while there was no difference of the time between the beginning of motor weakness and the maximum motor deficiency in the two groups. A treatment with ACTH and/or corticosteroids seemed not to influence the long term prognosis of the illness.", "contents": "[The Landry-Guillain-Barr\u00e9-Strohl-syndrome. Prognosis in adults (author's transl)]. The clinical aspect of acute polyradiculitis (Landry-Guillain-Barr\u00e9-Strohl syndrome) of 85 patients is resumed. 52 of these 85 patients were seen after an average of 5, 1 years, 8 were dead at the time of control and 25 could not be traced. Two patients died during the acute phase of polyradiculitis corresponding to a letality of 2%. 24 of the subjects (46%) had recovered completely, 28 (54%) showed some residual symptoms. Eleven patients (21%) had some residual weakness of hands and/or feet. Out of these eleven six (11% of total) were so much disabled that they received a disablement pension. 17 patients with slight sensory disturbances and/or some loss of reflexes were not handicapped in their every-day life. 20 patients were examined electrophysiologically during the follow-up. All the five patients with a pathological EMG also showed some clinical residual signs. A positive correlation between pathological conduction velocities in the median and/or deep peroneal nerve and clinical residua was only inconstantly found. Patients with severe tetraparesis during the acute phase had more often residual symptoms. The time from the maximum motor deficiency to the beginning of recovery was longer in the latter group than in patients without residual symptoms (23 respectively 8 days) while there was no difference of the time between the beginning of motor weakness and the maximum motor deficiency in the two groups. A treatment with ACTH and/or corticosteroids seemed not to influence the long term prognosis of the illness."}
{"id": "PMID:194826", "title": "Establishment and characterization of a cell line derived from a spontaneous murine lung carcinoma (M109).", "content": "The Madison lung (M109) tumor cell line, initiated from a \"spontaneous\", anaplastic murine lung carcinoma, has been propagated continuously in vitro for more than 300 cell generations. Cytogenetic analysis revealed a mouse karyotype with a mode of 78 chromosomes (2n = 40). Three distinct marker chromosomes were identified by trypsin-giemsa banding. The cells piled up in culture and had a short generation time and high plating efficiency. Electron microscopy revealed highly undifferentiated cells with little rough endoplasmic reticulum, an abundance of free polysomes, the presence of few and often odd-shaped mitochondria, lipid bodies and phagocytic vacuoles. Virus particles of the C-type were found frequently. The subcutaneous transplantation of M109 cultured cells at a relatively low cell inoculum produced highly metastatic tumors in syngeneic BALG/c mice.", "contents": "Establishment and characterization of a cell line derived from a spontaneous murine lung carcinoma (M109). The Madison lung (M109) tumor cell line, initiated from a \"spontaneous\", anaplastic murine lung carcinoma, has been propagated continuously in vitro for more than 300 cell generations. Cytogenetic analysis revealed a mouse karyotype with a mode of 78 chromosomes (2n = 40). Three distinct marker chromosomes were identified by trypsin-giemsa banding. The cells piled up in culture and had a short generation time and high plating efficiency. Electron microscopy revealed highly undifferentiated cells with little rough endoplasmic reticulum, an abundance of free polysomes, the presence of few and often odd-shaped mitochondria, lipid bodies and phagocytic vacuoles. Virus particles of the C-type were found frequently. The subcutaneous transplantation of M109 cultured cells at a relatively low cell inoculum produced highly metastatic tumors in syngeneic BALG/c mice."}
{"id": "PMID:194827", "title": "Induction of melanogenesis in vitro in the epidermal melanoblasts of newborn mouse skin by MSH.", "content": "The number of epidermal melanocytes positive to the dopa reaction increased when skin explants from newborn mice were cultured with MSH or dbc-AMP. These agents seem to induce melanogenesis in the pre-existing melanoblasts. This hormone-induced melanogenesis is suppressed by actinomycin D or cycloheximide, suggesting that the initiation of melanogenesis in the epidermal melanoblasts requires de novo transcription and translation.", "contents": "Induction of melanogenesis in vitro in the epidermal melanoblasts of newborn mouse skin by MSH. The number of epidermal melanocytes positive to the dopa reaction increased when skin explants from newborn mice were cultured with MSH or dbc-AMP. These agents seem to induce melanogenesis in the pre-existing melanoblasts. This hormone-induced melanogenesis is suppressed by actinomycin D or cycloheximide, suggesting that the initiation of melanogenesis in the epidermal melanoblasts requires de novo transcription and translation."}
{"id": "PMID:194828", "title": "Intercellular immunological controls and modulation of cyclic AMP levels. Some doubts.", "content": "We have re-examined two sets of observations put forward to support the hypothesis that rises in cAMP levels induced by vasoactive amines and prostaglandins are involved in the intercellular control of immunological and inflammatory processes. (1) This hypothesis is said to be supported by the fact that cholera toxin, which raises cAMP levels in lymphoid tissue in vivo, is immunosuppressive. However, we found that cholera toxin inhibited antibody production only if given in doses causing gross destruction of lymphoid tissue. This sort of evidence, therefore, cannot be used to support a hypothesis about homoeostasis under physiological conditions. (2) The hypothesis is also said to be supported by the claim that vasoactive amines, prostaglandins, cholera toxin and methyl xanthines, which raise cAMP levels in cells in vitro, also inhibit the formation of haemolytic plaques by spleen cells from mice immunized with sheep red cells. However, we were unable to confirm this claim, except when the experimental conditions were such that cells were killed or other artefacts operated.", "contents": "Intercellular immunological controls and modulation of cyclic AMP levels. Some doubts. We have re-examined two sets of observations put forward to support the hypothesis that rises in cAMP levels induced by vasoactive amines and prostaglandins are involved in the intercellular control of immunological and inflammatory processes. (1) This hypothesis is said to be supported by the fact that cholera toxin, which raises cAMP levels in lymphoid tissue in vivo, is immunosuppressive. However, we found that cholera toxin inhibited antibody production only if given in doses causing gross destruction of lymphoid tissue. This sort of evidence, therefore, cannot be used to support a hypothesis about homoeostasis under physiological conditions. (2) The hypothesis is also said to be supported by the claim that vasoactive amines, prostaglandins, cholera toxin and methyl xanthines, which raise cAMP levels in cells in vitro, also inhibit the formation of haemolytic plaques by spleen cells from mice immunized with sheep red cells. However, we were unable to confirm this claim, except when the experimental conditions were such that cells were killed or other artefacts operated."}
{"id": "PMID:194829", "title": "The action of thiols on lymphocyte membranes.", "content": "Short-term incubation with cysteine in concentrations not altering cell viability increased the amount of -SH groups on the surface of rat lymphocytes. Maximal effect was achieved in 10 min using 2 mM cysteine, which concentration also induced immediate total loss of response to adrenaline, as measured by intracellular cyclic AMP level. Neither of these effects was observed after incubation of lymphocytes with glutathione or dithiothreitol.", "contents": "The action of thiols on lymphocyte membranes. Short-term incubation with cysteine in concentrations not altering cell viability increased the amount of -SH groups on the surface of rat lymphocytes. Maximal effect was achieved in 10 min using 2 mM cysteine, which concentration also induced immediate total loss of response to adrenaline, as measured by intracellular cyclic AMP level. Neither of these effects was observed after incubation of lymphocytes with glutathione or dithiothreitol."}
{"id": "PMID:194830", "title": "Specific immune lysis of paramyxovirus-infected cells by H-2-compatible thymus-derived lymphocytes.", "content": "Mice exposed to paramyxovirus (Sendai) generate specifically sensitized thymus-derived lymphocytes (T cells) which, in an in vitro 51Cr release assay, interact only with virus-infected target cells sharing strong transplantation antigens. Reciprocal exclusion of cytotoxic T-cell activity is found for Sendai virus, lymphocytic choriomeningitis virus and ectromelia virus. Immune T cells are detected as early as 3 days after intraperitoneal inoculation with a large dose of Sendai virus, and cytotoxicity is generally maximal on days 5-7. Lysis is restricted to interactions where sensitized lymphocytes and virus-infected target cells (fibroblasts, tumour cells or macrophages) are compatible at the K or the D locus of one H-2 haplotype. Identity of immune response (Ir) genes is neither sufficient nor necessary. Levels of T-cell responsiveness show some variation with H-2 type. Cytotoxic T-cell activity associated with H-2b is less than that recognized for H-2k or H-2d. These differences are, however, not obviously related to Ir gene control.", "contents": "Specific immune lysis of paramyxovirus-infected cells by H-2-compatible thymus-derived lymphocytes. Mice exposed to paramyxovirus (Sendai) generate specifically sensitized thymus-derived lymphocytes (T cells) which, in an in vitro 51Cr release assay, interact only with virus-infected target cells sharing strong transplantation antigens. Reciprocal exclusion of cytotoxic T-cell activity is found for Sendai virus, lymphocytic choriomeningitis virus and ectromelia virus. Immune T cells are detected as early as 3 days after intraperitoneal inoculation with a large dose of Sendai virus, and cytotoxicity is generally maximal on days 5-7. Lysis is restricted to interactions where sensitized lymphocytes and virus-infected target cells (fibroblasts, tumour cells or macrophages) are compatible at the K or the D locus of one H-2 haplotype. Identity of immune response (Ir) genes is neither sufficient nor necessary. Levels of T-cell responsiveness show some variation with H-2 type. Cytotoxic T-cell activity associated with H-2b is less than that recognized for H-2k or H-2d. These differences are, however, not obviously related to Ir gene control."}
{"id": "PMID:194831", "title": "Serological relatedness of herpes simplex viruses. Type-specificity of antibody response.", "content": "The serological relatedness of forty-seven strains of type 1 and type 2 herpes simplex virus was investigated by reciprocal and non-reciprocal neutralization kinetics. Early rabbit antisera divided the virus strains into two distinct groups where confident indentification of virus type was possible. Hyperimmune mouse and rabbit antisera did not divide the two virus types into two distinct non-over-lapping groups. The extent of overlap varied with the particular attribute of the virus being studied. The virus types were best discriminated by their neutralizability by type 1 antisera and least well by their neutralizability by type 2 antisera. The results of reciprocal kinetic neutralization test with hyperimmune mouse antisera were analysed by multi-dimensional cluster analysis. Hyperimmune mouse or rabbit antisera could not be discriminated with respect to their immunogenic type by their absolute neutralization rate constants against either type 1 or type 2 virus, but could be distinguished on a group basis by their relative neutralizability against both virus types (antiserum specificity attribute); however, using this latter criterion, the type of immunogen could only be predicted in seven of the forty antisera under test. 'Early' mouse antisera could also be distinguished as groups by their absolute k-values against type 1 herpes virus. Thus, immunogenic identification, on other than a group basis, was unreliable. The specificity of a given serum was inversely related to its titre. There was a positive correlation between the specificity of a given virus strain and of its corresponding antiserum.", "contents": "Serological relatedness of herpes simplex viruses. Type-specificity of antibody response. The serological relatedness of forty-seven strains of type 1 and type 2 herpes simplex virus was investigated by reciprocal and non-reciprocal neutralization kinetics. Early rabbit antisera divided the virus strains into two distinct groups where confident indentification of virus type was possible. Hyperimmune mouse and rabbit antisera did not divide the two virus types into two distinct non-over-lapping groups. The extent of overlap varied with the particular attribute of the virus being studied. The virus types were best discriminated by their neutralizability by type 1 antisera and least well by their neutralizability by type 2 antisera. The results of reciprocal kinetic neutralization test with hyperimmune mouse antisera were analysed by multi-dimensional cluster analysis. Hyperimmune mouse or rabbit antisera could not be discriminated with respect to their immunogenic type by their absolute neutralization rate constants against either type 1 or type 2 virus, but could be distinguished on a group basis by their relative neutralizability against both virus types (antiserum specificity attribute); however, using this latter criterion, the type of immunogen could only be predicted in seven of the forty antisera under test. 'Early' mouse antisera could also be distinguished as groups by their absolute k-values against type 1 herpes virus. Thus, immunogenic identification, on other than a group basis, was unreliable. The specificity of a given serum was inversely related to its titre. There was a positive correlation between the specificity of a given virus strain and of its corresponding antiserum."}
{"id": "PMID:194832", "title": "Immunoglobulin synthesis by an SV-40-induced hamster lymphoma.", "content": "A transplantable lymphoid tumour induced in Syrian hamsters by SV-40 was shown to synthesize a 7Sgamma2 monoclonal immunoglobulin of the same idiotype was also found in the membrane of the tumour cell. The induction of immunoglobulin synthesizing tumours by SV-40 should be useful for studies on immunoglobulin synthesis, lymphoid cell receptors and tumour immunity.", "contents": "Immunoglobulin synthesis by an SV-40-induced hamster lymphoma. A transplantable lymphoid tumour induced in Syrian hamsters by SV-40 was shown to synthesize a 7Sgamma2 monoclonal immunoglobulin of the same idiotype was also found in the membrane of the tumour cell. The induction of immunoglobulin synthesizing tumours by SV-40 should be useful for studies on immunoglobulin synthesis, lymphoid cell receptors and tumour immunity."}
{"id": "PMID:194833", "title": "The antigenicity of chondrocytes.", "content": "Stimulation in vitro of allogeneic and syngeneic mixed lymphocyte cultures suggests the presence of differentiation antigens on the surface of the chondrocyte. This may provide part of the answer to the nature of the chronicity of certain arthritic processes.", "contents": "The antigenicity of chondrocytes. Stimulation in vitro of allogeneic and syngeneic mixed lymphocyte cultures suggests the presence of differentiation antigens on the surface of the chondrocyte. This may provide part of the answer to the nature of the chronicity of certain arthritic processes."}
{"id": "PMID:194835", "title": "Peripheral blood lymphocyte response to acute infections in humans.", "content": "The response of subpopulations of peripheral venous blood lymphocytes to systemic bacterial or viral infections was studied. B-lymphocytes were defined by the presence of surface binding sites for mu chains, which were determined by immunofluorescent staining. T-lymphocytes were defined by the ability to form active sheep cell rosettes. Virus-infectible lymphocytes, which may represent activated T-lymphocytes, were defined by the ability to support virus replication. Patients with bacterial infections had an increase in the B-lymphocytes of peripheral venous blood, whereas patients with viral infections had an increase in T-lymphocytes as compared to controls. The number of virus-infectible lymphocytes was increased in patients with bacterial infections but not in patients with viral infections. These studies suggest that subpopulations of human peripheral blood lymphocytes vary in response to different types of infectious agents.", "contents": "Peripheral blood lymphocyte response to acute infections in humans. The response of subpopulations of peripheral venous blood lymphocytes to systemic bacterial or viral infections was studied. B-lymphocytes were defined by the presence of surface binding sites for mu chains, which were determined by immunofluorescent staining. T-lymphocytes were defined by the ability to form active sheep cell rosettes. Virus-infectible lymphocytes, which may represent activated T-lymphocytes, were defined by the ability to support virus replication. Patients with bacterial infections had an increase in the B-lymphocytes of peripheral venous blood, whereas patients with viral infections had an increase in T-lymphocytes as compared to controls. The number of virus-infectible lymphocytes was increased in patients with bacterial infections but not in patients with viral infections. These studies suggest that subpopulations of human peripheral blood lymphocytes vary in response to different types of infectious agents."}
{"id": "PMID:194836", "title": "Comparative effects of host and viral factors on early pathogenesis of Marek's disease.", "content": "A series of experiments on the early pathogenesis of Marek's disease was conducted according to a uniform scheme. In each experiment, there was a single variable-age, genetic strain, or virus strain. Virus assays from spleen, buffy coat, and bone marrow, and fluorescent antibody tests on spleen, bursa of Fabricius, and thymus were conducted on five birds per group daily from the 3rd through the 10th day postinoculation. From these data, it was apparent that the response could be divided into two periods: 4 to 6 days = early; 8 to 10 days = late. Serological tests showed all groups except the 1-day-old group to have neutralizing antibody by the end of the 10-day period. With few exceptions, none of the variables tested exerted any appreciable influence on the level of virus growth in spleen, bursa, or thymus during the early period. High levels of infection occurred in all birds during that period. Changes in infection pattern which occurred during the late period were significant and could be correlated with occurrence of Marek's disease in test samples of birds held until 7 weeks after infection. Infectivity levels dropped appreciably in the case of resistant N-line birds given JM virus, and, during the late period, infection levels were significantly higher in GA-infected birds than in those given viruses of lower virulence. Whereas the virus titers during the 8- to 10-day period usually reflected the eventual clinical pattern of Marek's disease, the levels of viral antigen (fluorescent antibody tests) were much less consistent. One further experiment conducted by the same uniform scheme demonstrated no significant effects on early pathogenesis or course of Marek's disease in birds given continuous oral medication with amino-ureido-sulfone.", "contents": "Comparative effects of host and viral factors on early pathogenesis of Marek's disease. A series of experiments on the early pathogenesis of Marek's disease was conducted according to a uniform scheme. In each experiment, there was a single variable-age, genetic strain, or virus strain. Virus assays from spleen, buffy coat, and bone marrow, and fluorescent antibody tests on spleen, bursa of Fabricius, and thymus were conducted on five birds per group daily from the 3rd through the 10th day postinoculation. From these data, it was apparent that the response could be divided into two periods: 4 to 6 days = early; 8 to 10 days = late. Serological tests showed all groups except the 1-day-old group to have neutralizing antibody by the end of the 10-day period. With few exceptions, none of the variables tested exerted any appreciable influence on the level of virus growth in spleen, bursa, or thymus during the early period. High levels of infection occurred in all birds during that period. Changes in infection pattern which occurred during the late period were significant and could be correlated with occurrence of Marek's disease in test samples of birds held until 7 weeks after infection. Infectivity levels dropped appreciably in the case of resistant N-line birds given JM virus, and, during the late period, infection levels were significantly higher in GA-infected birds than in those given viruses of lower virulence. Whereas the virus titers during the 8- to 10-day period usually reflected the eventual clinical pattern of Marek's disease, the levels of viral antigen (fluorescent antibody tests) were much less consistent. One further experiment conducted by the same uniform scheme demonstrated no significant effects on early pathogenesis or course of Marek's disease in birds given continuous oral medication with amino-ureido-sulfone."}
{"id": "PMID:194837", "title": "Human rotavirus in lambs: infection and passive protection.", "content": "A human stool filtrate containing rotavirus which was administered orally to gnotobiotic lambs caused diarrhea, virus excretion, development of antibodies to rotavirus, and pathological changes in the villi of the small intestine. Thus, lambs may serve as experimental animals for the study of human rotavirus infections. This model system was used to study passive protection. Human immunoglobulin G (IgG) containing antibody to rotavirus was fed to lambs 24 to 78 h after birth, and the lambs were infected with lamb-passaged human rotavirus when 30 h old. The lambs treated with IgG did not develop diarrhea, and virus excretion was delayed in onset and shortened in duration. It may be possible to make similar use of IgG to protect children at risk in a rotavirus outbreak. The treatment did not prevent the lambs developing antibody to rotavirus.", "contents": "Human rotavirus in lambs: infection and passive protection. A human stool filtrate containing rotavirus which was administered orally to gnotobiotic lambs caused diarrhea, virus excretion, development of antibodies to rotavirus, and pathological changes in the villi of the small intestine. Thus, lambs may serve as experimental animals for the study of human rotavirus infections. This model system was used to study passive protection. Human immunoglobulin G (IgG) containing antibody to rotavirus was fed to lambs 24 to 78 h after birth, and the lambs were infected with lamb-passaged human rotavirus when 30 h old. The lambs treated with IgG did not develop diarrhea, and virus excretion was delayed in onset and shortened in duration. It may be possible to make similar use of IgG to protect children at risk in a rotavirus outbreak. The treatment did not prevent the lambs developing antibody to rotavirus."}
{"id": "PMID:194834", "title": "The effect of imipramine on isolated skeletal muscle preparations.", "content": "Imipramine (2-10 microng/ml) noncompetitively inhibited acetylcholine responses of the frog rectus abdominis muscle, and markedly inhibited the contracture produced by carbachol and succinylcholine without affecting the contracture produced by KCl, caffeine, and chlorpromazine. The twitch responses to indirect and direct stimulation of the rat phrenic nerve-diaphragm and the frog sciatic nerve-gastrocnemius were first augmented and then depressed markedly and irreversibly by imipramine (5-20 microng/ml). The indirect stimulation was inhibited earlier and to a greater degree than the direct stimulation. The blockade in the nerve-sartorius developed and progressed quickly without prior augmented responses, and with a parallel time course for indirect and direct stimulation. On the frog rectus, physostigmine antagonised whereas d-tubocurarine and CaCl2 increased the imipramine-induced inhibition. In the nerve muscle preparations, physostigmine, CaCl2 and KCl did not affect the neuromuscular blockade produced by imipramine; tubocurarine (0.05 microng/ml) markedly increased the blocking effect of imipramine (20 microng/ml) on the rat phrenic nerve-diaphragm. The results have been discussed in relation to the memberane stabilizing and the calcium releasing actions of imipramine.", "contents": "The effect of imipramine on isolated skeletal muscle preparations. Imipramine (2-10 microng/ml) noncompetitively inhibited acetylcholine responses of the frog rectus abdominis muscle, and markedly inhibited the contracture produced by carbachol and succinylcholine without affecting the contracture produced by KCl, caffeine, and chlorpromazine. The twitch responses to indirect and direct stimulation of the rat phrenic nerve-diaphragm and the frog sciatic nerve-gastrocnemius were first augmented and then depressed markedly and irreversibly by imipramine (5-20 microng/ml). The indirect stimulation was inhibited earlier and to a greater degree than the direct stimulation. The blockade in the nerve-sartorius developed and progressed quickly without prior augmented responses, and with a parallel time course for indirect and direct stimulation. On the frog rectus, physostigmine antagonised whereas d-tubocurarine and CaCl2 increased the imipramine-induced inhibition. In the nerve muscle preparations, physostigmine, CaCl2 and KCl did not affect the neuromuscular blockade produced by imipramine; tubocurarine (0.05 microng/ml) markedly increased the blocking effect of imipramine (20 microng/ml) on the rat phrenic nerve-diaphragm. The results have been discussed in relation to the memberane stabilizing and the calcium releasing actions of imipramine."}
{"id": "PMID:194838", "title": "Cell-mediated cytotoxicity to herpes-infected cells in humans: dependence on antibodies.", "content": "Herpes simplex virus type 1 (HSV-1)-infected human skin fibroblasts were used as target cells in a 51Cr release assay, using peripheral blood mononuclear cells from HSV-seropositive and -seronegative donors as effector cells. Cytotoxicity was exerted by ordinarily prepared lymphoid cells but could be reduced by extensive washing of the effector cells. The antibody dependence of the system was shown by the recovery of activity through addition of positive serum or medium used for the early washes of effector cells. Three donors found to be seronegative in the usual serological tests were shown to be seropositive in this test. It is proposed that the assay can be used as a very sensitive serological test.", "contents": "Cell-mediated cytotoxicity to herpes-infected cells in humans: dependence on antibodies. Herpes simplex virus type 1 (HSV-1)-infected human skin fibroblasts were used as target cells in a 51Cr release assay, using peripheral blood mononuclear cells from HSV-seropositive and -seronegative donors as effector cells. Cytotoxicity was exerted by ordinarily prepared lymphoid cells but could be reduced by extensive washing of the effector cells. The antibody dependence of the system was shown by the recovery of activity through addition of positive serum or medium used for the early washes of effector cells. Three donors found to be seronegative in the usual serological tests were shown to be seropositive in this test. It is proposed that the assay can be used as a very sensitive serological test."}
{"id": "PMID:194839", "title": "Effector cell involved in cell-mediated cytotoxicity to cells infected with herpes simplex virus type 1.", "content": "Experiments were performed to analyze the characteristics of the effector cells involved in cell-mediated killing of herpes-infected fibroblasts. Effector cells were fractionated according to adherence and phagocytic properties, and lymphocytes were depleted of T-cells, and EA- and EAC- (antibody-coated bovine erythrocytes and bovine erythrocytes coated with rabbit anti-bovine antibodies and C5-deficient mouse serum, respectively) rosette-forming cells by differential centrifugation. Column passage was used as an alternative to depletion of B-cells and F(c)-receptor-positive cells. Antibody-dependent, cell-mediated cytotoxicity was found to be associated with nonphagocytic cells carrying low-avidity F(c) receptors. Some of these had surface immunoglobulin; others lacked both B- and T-cell markers. Low levels of killing were found without addition of anti-herpes antibody to the test system, and this killing seemed to depend on cells belonging to the same subpopulation as the antibody-dependent effector cells.", "contents": "Effector cell involved in cell-mediated cytotoxicity to cells infected with herpes simplex virus type 1. Experiments were performed to analyze the characteristics of the effector cells involved in cell-mediated killing of herpes-infected fibroblasts. Effector cells were fractionated according to adherence and phagocytic properties, and lymphocytes were depleted of T-cells, and EA- and EAC- (antibody-coated bovine erythrocytes and bovine erythrocytes coated with rabbit anti-bovine antibodies and C5-deficient mouse serum, respectively) rosette-forming cells by differential centrifugation. Column passage was used as an alternative to depletion of B-cells and F(c)-receptor-positive cells. Antibody-dependent, cell-mediated cytotoxicity was found to be associated with nonphagocytic cells carrying low-avidity F(c) receptors. Some of these had surface immunoglobulin; others lacked both B- and T-cell markers. Low levels of killing were found without addition of anti-herpes antibody to the test system, and this killing seemed to depend on cells belonging to the same subpopulation as the antibody-dependent effector cells."}
{"id": "PMID:194840", "title": "Passive immunity to feline leukemia: evaluation of immunity from dams naturally infected and experimentally vaccinated.", "content": "Antibodies against feline leukemia virus (FeLV) and the feline oncornavirus-associated cell membrane antigen (FOCMA) were transferred from pregnant cats to their suckling kittens. All of these kittens were protected against infection and oncogenesis by virulent FeLV when challenged at 2 weeks of age. Suckling kittens acquired 25 to 100% of maternal virus-neutralizing and FOCMA titers by 3 days of age, and titers underwent linear decay to undetectable levels by 2 to 3 months of age. FOCMA antibody in dams and kittens was identified as immunoglobulin G (IgG) by use of goat anti-human IgG serum, which cross-reacts with feline IgG in the indirect membrane immunofluorescence test for FOCMA antibody. In an attempt to induce protective maternal antibody by vaccination, 10 pregnant cats were immunized by three to five weekly intramuscular injections with purified FeLV inactivated by ultraviolet irradiation. After the course of immunization, neither virus-neutralizing nor FOCMA antibody was detectable in the dams or in 19 kittens born to these cats. When these kittens were challenged with FeLV at 2 weeks of age, 18 of 19 developed persistent viremia and FeLV-related disease.", "contents": "Passive immunity to feline leukemia: evaluation of immunity from dams naturally infected and experimentally vaccinated. Antibodies against feline leukemia virus (FeLV) and the feline oncornavirus-associated cell membrane antigen (FOCMA) were transferred from pregnant cats to their suckling kittens. All of these kittens were protected against infection and oncogenesis by virulent FeLV when challenged at 2 weeks of age. Suckling kittens acquired 25 to 100% of maternal virus-neutralizing and FOCMA titers by 3 days of age, and titers underwent linear decay to undetectable levels by 2 to 3 months of age. FOCMA antibody in dams and kittens was identified as immunoglobulin G (IgG) by use of goat anti-human IgG serum, which cross-reacts with feline IgG in the indirect membrane immunofluorescence test for FOCMA antibody. In an attempt to induce protective maternal antibody by vaccination, 10 pregnant cats were immunized by three to five weekly intramuscular injections with purified FeLV inactivated by ultraviolet irradiation. After the course of immunization, neither virus-neutralizing nor FOCMA antibody was detectable in the dams or in 19 kittens born to these cats. When these kittens were challenged with FeLV at 2 weeks of age, 18 of 19 developed persistent viremia and FeLV-related disease."}
{"id": "PMID:194841", "title": "Protection against herpes simplex virus infection in mice by Corynebacterium parvum.", "content": "Corynebacterium parvum administered in mice prior to herpes simplex virus (HSV) infection significantly protected them against lethal encephalitis. This was seen both with a mouse strain highly susceptible to HSV and with one relatively resistant to HSV. Mice immunosuppressed by cyclophosphamide and showing an increased mortality after HSV infection were also protected by C. parvum pretreatment. However, C. parvum given simultaneously with or after HSV infection did not exert a therapeutic effect.", "contents": "Protection against herpes simplex virus infection in mice by Corynebacterium parvum. Corynebacterium parvum administered in mice prior to herpes simplex virus (HSV) infection significantly protected them against lethal encephalitis. This was seen both with a mouse strain highly susceptible to HSV and with one relatively resistant to HSV. Mice immunosuppressed by cyclophosphamide and showing an increased mortality after HSV infection were also protected by C. parvum pretreatment. However, C. parvum given simultaneously with or after HSV infection did not exert a therapeutic effect."}
{"id": "PMID:194842", "title": "Increase in serum IgE levels of ovalbumin-sensitized cats and the detection of elastase and collagenase activities in secretions of sensitized feline alveolar macrophages challenged in vitro.", "content": "The feline model of respiratory hypersensitivity induced by intraperitoneal injection of ovalbumin has been studied. IgE serum antibodies were present for 3-10 weeks following sensitization, with maximum titers occurring between 50 and 70 days. Similarly, peak passive cutaneous anaphylaxis reactions occurred between 50 and 70 days. Alveolar macrophages, obtained by tracheal lavage at 65 days after sensitization, produced elastase like and collagenase-like secretions 48 h after challenge with ovalbumin in culture. Macrophages from nonsensitized cats did not produce these secretions. It is hypothesized that reaginic antibodies and sensitized alveolar macrophages, such as those found in the cat model, may be responsible in part for the destruction of lung tissue found in long-term respiratory diseases, similar to fibrosing alveolitis and pulmonary emphysema in man.", "contents": "Increase in serum IgE levels of ovalbumin-sensitized cats and the detection of elastase and collagenase activities in secretions of sensitized feline alveolar macrophages challenged in vitro. The feline model of respiratory hypersensitivity induced by intraperitoneal injection of ovalbumin has been studied. IgE serum antibodies were present for 3-10 weeks following sensitization, with maximum titers occurring between 50 and 70 days. Similarly, peak passive cutaneous anaphylaxis reactions occurred between 50 and 70 days. Alveolar macrophages, obtained by tracheal lavage at 65 days after sensitization, produced elastase like and collagenase-like secretions 48 h after challenge with ovalbumin in culture. Macrophages from nonsensitized cats did not produce these secretions. It is hypothesized that reaginic antibodies and sensitized alveolar macrophages, such as those found in the cat model, may be responsible in part for the destruction of lung tissue found in long-term respiratory diseases, similar to fibrosing alveolitis and pulmonary emphysema in man."}
{"id": "PMID:194843", "title": "Preferential enhancement of IgE antibody formation by Bordetella pertussis.", "content": "Preferential enhancement of IgE antibody response was observed in BALF/c mice by the administration of Bordetella pertussis with antigen (DNP-Salmonella). Correlation between B cell mitogenic activity and adjuvant action among B. pertussis, Salmonella, lipopolysaccharide of Escherichia coli and Ficoll was examined but was not found. Thymus-derived cells seemed necessary to develop adjuvant action of B. pertussis since antibody response in athymic nude mice was not influenced by B. pertussis. Helper function of adoptively transfered spleen cells was enhanced by immunization of the donor mice with carrier antigen in the presence of B. pertussis. The magnitude of enhancement was greatest in IgE class. The results indicated that preferential enhancement of IgE antibody formation by B. pertussis is mediated by the augmentation of carrier-specific helper function.", "contents": "Preferential enhancement of IgE antibody formation by Bordetella pertussis. Preferential enhancement of IgE antibody response was observed in BALF/c mice by the administration of Bordetella pertussis with antigen (DNP-Salmonella). Correlation between B cell mitogenic activity and adjuvant action among B. pertussis, Salmonella, lipopolysaccharide of Escherichia coli and Ficoll was examined but was not found. Thymus-derived cells seemed necessary to develop adjuvant action of B. pertussis since antibody response in athymic nude mice was not influenced by B. pertussis. Helper function of adoptively transfered spleen cells was enhanced by immunization of the donor mice with carrier antigen in the presence of B. pertussis. The magnitude of enhancement was greatest in IgE class. The results indicated that preferential enhancement of IgE antibody formation by B. pertussis is mediated by the augmentation of carrier-specific helper function."}
{"id": "PMID:194844", "title": "Differential induction of Epstein-Barr virus-related antigens in heterokaryon cultures.", "content": "Different paterns of induction of Epstein-Barr virus (EBV)-related antigens were observed in heterokaryons produced by Sendai virus-mediated fusion of producer and non-producer human lymphoblastoid cells with various other cell types. EBV-related early antigens (EA) and viral capsid antigen (VCA) could obviously be induced in heterokaryons between producer cells (P3HR-1 and QIMR-WIL), normally expressing these natigens at very low frequency, and human FL or HeLa cells. Positive cells were detected as early as 3 h after fusion and there often followed a rapid increase in positive cells. In contrast, in heterokaryons between non-producer cells (Raji and NC-37) and FL or HeLa cells, only EA but not VCA was induced. EA induction was also evident in fusion of human lymphoblastoid cells with monkey cells (Vero) but with mouse cells (L-M(TK-) C11D and MCB-2) no EBV induction occurred. The EBV induction in heterokaryons was significantly enhanced by 5-iododeoxyuridine treatment.", "contents": "Differential induction of Epstein-Barr virus-related antigens in heterokaryon cultures. Different paterns of induction of Epstein-Barr virus (EBV)-related antigens were observed in heterokaryons produced by Sendai virus-mediated fusion of producer and non-producer human lymphoblastoid cells with various other cell types. EBV-related early antigens (EA) and viral capsid antigen (VCA) could obviously be induced in heterokaryons between producer cells (P3HR-1 and QIMR-WIL), normally expressing these natigens at very low frequency, and human FL or HeLa cells. Positive cells were detected as early as 3 h after fusion and there often followed a rapid increase in positive cells. In contrast, in heterokaryons between non-producer cells (Raji and NC-37) and FL or HeLa cells, only EA but not VCA was induced. EA induction was also evident in fusion of human lymphoblastoid cells with monkey cells (Vero) but with mouse cells (L-M(TK-) C11D and MCB-2) no EBV induction occurred. The EBV induction in heterokaryons was significantly enhanced by 5-iododeoxyuridine treatment."}
{"id": "PMID:194845", "title": "Comparative studies on adult donor lymphocytes infected by EB virus in vivo or in vitro: origin of transformed cells arising in co-cultures with foetal lymphocytes.", "content": "Co-cultures were set up between equal numbers of mononuclear cells from the blood of EB virus-infected individuals, either acute IM patients or healthy seropositive adult donors, and foetal cord blood mononuclear cells of the opposite sex. The cell lines arising in the co-cultures were of mixed origin, with foetal cells predominating in many cases. In contrast, when mononuclear cells from seronegative adult donors were first infected with EB virus in vitro and then 5 to 12 days later co-cultured with a large excess of foetal cells of the opposite sex, the cell lines which arose were almost exclusively derived from the adult donor despite the fact that a small minority of the virus-infected adult cells released infectious virus capable of transforming the co-cultivated foetal cells. The experiments suggest that EB virus-infected cells present in the blood of IM patients and seropositive donors do not possess the capacity for unlimited in vitro growth shown by seronegative adult donor lymphocytes experimentally infected with the virus.", "contents": "Comparative studies on adult donor lymphocytes infected by EB virus in vivo or in vitro: origin of transformed cells arising in co-cultures with foetal lymphocytes. Co-cultures were set up between equal numbers of mononuclear cells from the blood of EB virus-infected individuals, either acute IM patients or healthy seropositive adult donors, and foetal cord blood mononuclear cells of the opposite sex. The cell lines arising in the co-cultures were of mixed origin, with foetal cells predominating in many cases. In contrast, when mononuclear cells from seronegative adult donors were first infected with EB virus in vitro and then 5 to 12 days later co-cultured with a large excess of foetal cells of the opposite sex, the cell lines which arose were almost exclusively derived from the adult donor despite the fact that a small minority of the virus-infected adult cells released infectious virus capable of transforming the co-cultivated foetal cells. The experiments suggest that EB virus-infected cells present in the blood of IM patients and seropositive donors do not possess the capacity for unlimited in vitro growth shown by seronegative adult donor lymphocytes experimentally infected with the virus."}
{"id": "PMID:194846", "title": "Bovine leukemia virus specific antibodies among French cattle. I. Comparison of complement fixation and hematological tests.", "content": "Complement fixation (CF) and hematological studies were performed on 517 cows living in normal conditions in different geographical areas of France. The animals belonged to three different categories: (1) multiple or single case herds, in which lymphosarcomas had been detected in the past five years. (2) Leukemia free herds of high risk regions. (3) Leukemia free and apparently unexposed herds. Positive animals were found with both methods in the first two categories but not in the third. Persistent lymphocytosis and CF antibodies were more frequent in leukemia than in exposed but leukemia free herds. Approximately 2 times more animals were found positive by serologic than by hematologic tests. The mean geometrical titer of CF antibodies was higher in lymphocytotic than in normal animals and highest in lymphosarcomatous cows. Persistent lymphocytosis was first detected in 3-years-old animals whereas 22% of younger cows were positive in the CF test.", "contents": "Bovine leukemia virus specific antibodies among French cattle. I. Comparison of complement fixation and hematological tests. Complement fixation (CF) and hematological studies were performed on 517 cows living in normal conditions in different geographical areas of France. The animals belonged to three different categories: (1) multiple or single case herds, in which lymphosarcomas had been detected in the past five years. (2) Leukemia free herds of high risk regions. (3) Leukemia free and apparently unexposed herds. Positive animals were found with both methods in the first two categories but not in the third. Persistent lymphocytosis and CF antibodies were more frequent in leukemia than in exposed but leukemia free herds. Approximately 2 times more animals were found positive by serologic than by hematologic tests. The mean geometrical titer of CF antibodies was higher in lymphocytotic than in normal animals and highest in lymphosarcomatous cows. Persistent lymphocytosis was first detected in 3-years-old animals whereas 22% of younger cows were positive in the CF test."}
{"id": "PMID:194848", "title": "Immunologic studies of the low molecular weight DNA binding protein of murine oncornaviruses.", "content": "A low molecular weight, highly basic DNA-binding protein was purified from several oncornaviruses by the sequential procedures of gel filtration in guanidine-hydrochloride, DEAE-cellulose chromatography and affinity chromatography on single-stranded DNA sepharose. The binding protein from Rauscher and woolly monkey type-C viruses was the fastest migrating of the virion proteins in SDS-polyacrylamide gels and thus is designated p10 according to previous convention although our estimates of molecular weight were 8-9,000 daltons. The binding protein from these two viruses was resolved into two bands by acid-urea electrophoresis although only a single NH2 terminal amino acid was detected (S. Oroszlan, personal communication), thus indicating charge heterogeneity. Antibody to Rauscher virus p10 species-specific in gel diffusion and complement-fixation tests and did not exhibit cross-reactivity with other virion proteins. A DNA-binding protein was also detected in preparations of mouse mammary tumor virus. This purified protein had an apparent molecular weight of 12,500, was the second fastest migrating component in the virus preparations, and was antigenically unrelated to the mouse type-C virus p10.", "contents": "Immunologic studies of the low molecular weight DNA binding protein of murine oncornaviruses. A low molecular weight, highly basic DNA-binding protein was purified from several oncornaviruses by the sequential procedures of gel filtration in guanidine-hydrochloride, DEAE-cellulose chromatography and affinity chromatography on single-stranded DNA sepharose. The binding protein from Rauscher and woolly monkey type-C viruses was the fastest migrating of the virion proteins in SDS-polyacrylamide gels and thus is designated p10 according to previous convention although our estimates of molecular weight were 8-9,000 daltons. The binding protein from these two viruses was resolved into two bands by acid-urea electrophoresis although only a single NH2 terminal amino acid was detected (S. Oroszlan, personal communication), thus indicating charge heterogeneity. Antibody to Rauscher virus p10 species-specific in gel diffusion and complement-fixation tests and did not exhibit cross-reactivity with other virion proteins. A DNA-binding protein was also detected in preparations of mouse mammary tumor virus. This purified protein had an apparent molecular weight of 12,500, was the second fastest migrating component in the virus preparations, and was antigenically unrelated to the mouse type-C virus p10."}
{"id": "PMID:194849", "title": "Incomplete viral genome in a non-virogenic mouse tumour cell line (RVP3) transformed by Prague strain of avian sarcoma virus.", "content": "Two cell lines, RVP3 and RVA4, derived originally from mouse tumors induced by the Prague and Schmidt-Ruppin strain of RSV, respectively, were studied. tall attempts failed to induce infectious virus production in RVP3 cells by fusion with chicken fibroblasts even if the cells were infected with avian leukosis viruses. Also, attempts to rescue the viral genome by transfection were unsuccessful. RVP3 cells harboured 31-45% of the viral genome sequences, as was shown by molecular hybridization, and therefore they were designated cryptovirogenic. The tumour cell line RVA4 did not contain any detectable viral sequences. The significance of the detection of the incomplete Rous virus genome sequences in mammalian cells is discussed.", "contents": "Incomplete viral genome in a non-virogenic mouse tumour cell line (RVP3) transformed by Prague strain of avian sarcoma virus. Two cell lines, RVP3 and RVA4, derived originally from mouse tumors induced by the Prague and Schmidt-Ruppin strain of RSV, respectively, were studied. tall attempts failed to induce infectious virus production in RVP3 cells by fusion with chicken fibroblasts even if the cells were infected with avian leukosis viruses. Also, attempts to rescue the viral genome by transfection were unsuccessful. RVP3 cells harboured 31-45% of the viral genome sequences, as was shown by molecular hybridization, and therefore they were designated cryptovirogenic. The tumour cell line RVA4 did not contain any detectable viral sequences. The significance of the detection of the incomplete Rous virus genome sequences in mammalian cells is discussed."}
{"id": "PMID:194850", "title": "Circadian variation in plasma melanocyte stimulating hormone activity in the rat.", "content": "Non--stress levels of plasma melanocyte stimulating hormone (MSH) and corticosterone were determined at 3-h intervals during controlled light--dark cycles in adult, male rats. Significant 24-h periodicity was demonstrated for both plasma MSH and corticosterone. Whereas plasma MSH values were not as high during the early evening hours as during the early morning hours, plasma corticosterone levels showed a marked rise during the early afternoon and crest values occurred just before the lights off phase of the 24-h light--dark cycle. These results indicate that in the rat, the level of MSH in plasma fluctuates with a low amplitude circadian frequency which is not in phase with that observed for plasma corticosterone.", "contents": "Circadian variation in plasma melanocyte stimulating hormone activity in the rat. Non--stress levels of plasma melanocyte stimulating hormone (MSH) and corticosterone were determined at 3-h intervals during controlled light--dark cycles in adult, male rats. Significant 24-h periodicity was demonstrated for both plasma MSH and corticosterone. Whereas plasma MSH values were not as high during the early evening hours as during the early morning hours, plasma corticosterone levels showed a marked rise during the early afternoon and crest values occurred just before the lights off phase of the 24-h light--dark cycle. These results indicate that in the rat, the level of MSH in plasma fluctuates with a low amplitude circadian frequency which is not in phase with that observed for plasma corticosterone."}
{"id": "PMID:194854", "title": "E.s.r. of spin-trapped radicals in aqueous solutions of amino acids. Reactions of the hydroxyl radical.", "content": "The radicals produced by reactions of hydroxyl radicals with amino acids in aqueous solutions have been investigated. Hydroxyl radicals were formed by U.V.-photolysis of hydrogen peroxide and the short-lived amino acid radicals were spin-trapped by tert-nitrosobutane and identified by electron spin resonance spectroscopy. Nineteen amino acids were studied, and several radicals were identified which have not been observed previously by other methods. Only side-chain radicals were identified for alanine, threonine, aspartic acid, asparagine, lysine, phenylalanine, tyrosine, proline and hydroxyproline; whereas for glycine the C(2) carbon radical was spin-trapped. Both C(2) carbon radicals and side-chain radicals were assigned to valine, leucine, isoleucine, serine, glutamic acid, glutamine, arginine and methionine.", "contents": "E.s.r. of spin-trapped radicals in aqueous solutions of amino acids. Reactions of the hydroxyl radical. The radicals produced by reactions of hydroxyl radicals with amino acids in aqueous solutions have been investigated. Hydroxyl radicals were formed by U.V.-photolysis of hydrogen peroxide and the short-lived amino acid radicals were spin-trapped by tert-nitrosobutane and identified by electron spin resonance spectroscopy. Nineteen amino acids were studied, and several radicals were identified which have not been observed previously by other methods. Only side-chain radicals were identified for alanine, threonine, aspartic acid, asparagine, lysine, phenylalanine, tyrosine, proline and hydroxyproline; whereas for glycine the C(2) carbon radical was spin-trapped. Both C(2) carbon radicals and side-chain radicals were assigned to valine, leucine, isoleucine, serine, glutamic acid, glutamine, arginine and methionine."}
{"id": "PMID:194851", "title": "Cytochemical evidence for aerobic pathways in Mycobacterium lepraemurium.", "content": "Three enzymes of aerobic pathways (cytochrome c oxidase, peroxidase and catalase) and one key enzyme of the tricarboxylic acid cycle (succinate dehydrogenase) were investigated for their ultrastructural localization in M. lepraemurium in infected mouse liver and in cultures of M. fortuitum as a control. All four enzymes were localized in M. fortuitum. To M. lepraemurium only cytochrome c oxidase and peroxidatic activity were detected. The localization of the latter enzyme activity was different compared with M. fortuitum. Succinate dehydrogenase was not detected in M. lepraemurium but rather surprisingly was found in the membrane of the phagosomes containing the bacteria. It is concluded that M. lepraemurium can function aerobically and has either a glyoxalate pathway or is an obligate autotroph.", "contents": "Cytochemical evidence for aerobic pathways in Mycobacterium lepraemurium. Three enzymes of aerobic pathways (cytochrome c oxidase, peroxidase and catalase) and one key enzyme of the tricarboxylic acid cycle (succinate dehydrogenase) were investigated for their ultrastructural localization in M. lepraemurium in infected mouse liver and in cultures of M. fortuitum as a control. All four enzymes were localized in M. fortuitum. To M. lepraemurium only cytochrome c oxidase and peroxidatic activity were detected. The localization of the latter enzyme activity was different compared with M. fortuitum. Succinate dehydrogenase was not detected in M. lepraemurium but rather surprisingly was found in the membrane of the phagosomes containing the bacteria. It is concluded that M. lepraemurium can function aerobically and has either a glyoxalate pathway or is an obligate autotroph."}
{"id": "PMID:194861", "title": "The effect of theophylline on the breakdown of the blood-aqueous barrier in the rabbit eye.", "content": "A disruption of the blood-aqueous barrier in rabbit eyes was elicited by topical prostaglandin E2, infrared irradiation of the iris, or subcutaneous alpha-melanocyte stimulating hormone (alpha-MSH). The course of the inflammatory reaction was followed by photoelectrical measurements of the aqueous flare in the anterior chamber. Pretreatment with intravenous theophylline, a phosphodiesterase inhibitor, significantly increased the protein leakage caused by prostaglandin E2 and alpha-MSH, but the response to infrared irradiation was slightly but not significantly enhanced. Intravenous theophylline given in higher doses caused per se an aqueous flare increase, which could not be inhibited by pretreatment with topical indomethacin. Our results indirectly indicate that accumulation of intraocular cAMP promotes a barrier damage and that cAMP might be the common effector of the barrier breakdown caused by prostaglandin as well as by nonprostaglandin agents.", "contents": "The effect of theophylline on the breakdown of the blood-aqueous barrier in the rabbit eye. A disruption of the blood-aqueous barrier in rabbit eyes was elicited by topical prostaglandin E2, infrared irradiation of the iris, or subcutaneous alpha-melanocyte stimulating hormone (alpha-MSH). The course of the inflammatory reaction was followed by photoelectrical measurements of the aqueous flare in the anterior chamber. Pretreatment with intravenous theophylline, a phosphodiesterase inhibitor, significantly increased the protein leakage caused by prostaglandin E2 and alpha-MSH, but the response to infrared irradiation was slightly but not significantly enhanced. Intravenous theophylline given in higher doses caused per se an aqueous flare increase, which could not be inhibited by pretreatment with topical indomethacin. Our results indirectly indicate that accumulation of intraocular cAMP promotes a barrier damage and that cAMP might be the common effector of the barrier breakdown caused by prostaglandin as well as by nonprostaglandin agents."}
{"id": "PMID:194862", "title": "Adenylate cyclase and phosphodiesterase activity in rabbit ureter.", "content": "Adenylate cyclase and phosphodiesterase enzyme activities were demonstrated in rabbit ureter. NaF, 10 mM, caused a 60.9 per cent increase in adenylate cyclase activity. Isoproterenol, 5 X 10-7 to 10-5 M induced a statistically significant dose-dependent increase in adenylate cyclase activity which was suppressed by propranolol, 10-7 M. Theophylline, 5 X 10-5 to 10-2 M, significantly inhibited phosphodiesterase activity. Thus, isoproterenol and theophylline, two agents that can relax ureteral segments previously contracted by a depolarizing concentration of potassium, could presumably increase cyclic AMP levels, isoproterenol by increasing synthesis and theophylline by decreasing degradation.", "contents": "Adenylate cyclase and phosphodiesterase activity in rabbit ureter. Adenylate cyclase and phosphodiesterase enzyme activities were demonstrated in rabbit ureter. NaF, 10 mM, caused a 60.9 per cent increase in adenylate cyclase activity. Isoproterenol, 5 X 10-7 to 10-5 M induced a statistically significant dose-dependent increase in adenylate cyclase activity which was suppressed by propranolol, 10-7 M. Theophylline, 5 X 10-5 to 10-2 M, significantly inhibited phosphodiesterase activity. Thus, isoproterenol and theophylline, two agents that can relax ureteral segments previously contracted by a depolarizing concentration of potassium, could presumably increase cyclic AMP levels, isoproterenol by increasing synthesis and theophylline by decreasing degradation."}
{"id": "PMID:194863", "title": "Activities of the androgen-responsive receptor of the prostatic plasma membrane.", "content": "Evidence of the presence of an androgen-activated \"gatekeeper\" receptor in the human prostate plasma membrane is presented. Not only does testosterone in vitro very rapidly accelerate uptake of alpha-aminoisobutyric acid into prostate slices but also its metabolite, dihydrotestosterone, greatly increases the rates of phosphorylation and dephosphorylation of the cation-dependent ATPase of isolated membranes. The relationship of this regulatory unit to prostatic physiologic processes is discussed.", "contents": "Activities of the androgen-responsive receptor of the prostatic plasma membrane. Evidence of the presence of an androgen-activated \"gatekeeper\" receptor in the human prostate plasma membrane is presented. Not only does testosterone in vitro very rapidly accelerate uptake of alpha-aminoisobutyric acid into prostate slices but also its metabolite, dihydrotestosterone, greatly increases the rates of phosphorylation and dephosphorylation of the cation-dependent ATPase of isolated membranes. The relationship of this regulatory unit to prostatic physiologic processes is discussed."}
{"id": "PMID:194864", "title": "The direct effect of ultrasound upon Wilms' tumor in the rat.", "content": "The possible activation of immunologic defenses against tumor by local ultrasonic irradiation was investigated. Sonication of one tumor of a dual implant destroyed that tumor only with no contralateral effect. Injection of tumor cells previously sonicated in vivo did not induced immunity to subsequent challenge with live cells. Immunofluorescent staining of host kidneys for antibody complexes was negative. It was concluded that sonication was only effective when directly applied to the tumor.", "contents": "The direct effect of ultrasound upon Wilms' tumor in the rat. The possible activation of immunologic defenses against tumor by local ultrasonic irradiation was investigated. Sonication of one tumor of a dual implant destroyed that tumor only with no contralateral effect. Injection of tumor cells previously sonicated in vivo did not induced immunity to subsequent challenge with live cells. Immunofluorescent staining of host kidneys for antibody complexes was negative. It was concluded that sonication was only effective when directly applied to the tumor."}
{"id": "PMID:194865", "title": "Further biological properties of the human syncytial virus.", "content": "Some biological properties of the human syncytial virus have been examined. A 13-day plaque assay in whole human embryo fibroblasts (HEF) has been developed using a liquid (growth medium) overlay. The plaques were 0.7-2 mm in diameter and often showed a clear central zone with irregular edges. Pretreatment of HEF monolayers with the polycation DEAE-dextran for either 30 min or 1 h was found to enhance plaque formation by a factor of from 2- to 7-fold. The plaque assay procedure required cell cultures undergoing active cell division. Adsorption kinetics and growth cycle studies in HEF indicated a relatively long adsorption period (3 h) and a relatively prolonged latent period of 24 h. Even under optimal conditions, virus yields were low and did not exceed 1 PFU per infected cell. Like other animal syncytium-forming 'foamy' viruses, the human virus induced both intranuclear and cytoplasmic antigens detectable by immmunofluorescence and was also markedly labile to freezing and thawing.", "contents": "Further biological properties of the human syncytial virus. Some biological properties of the human syncytial virus have been examined. A 13-day plaque assay in whole human embryo fibroblasts (HEF) has been developed using a liquid (growth medium) overlay. The plaques were 0.7-2 mm in diameter and often showed a clear central zone with irregular edges. Pretreatment of HEF monolayers with the polycation DEAE-dextran for either 30 min or 1 h was found to enhance plaque formation by a factor of from 2- to 7-fold. The plaque assay procedure required cell cultures undergoing active cell division. Adsorption kinetics and growth cycle studies in HEF indicated a relatively long adsorption period (3 h) and a relatively prolonged latent period of 24 h. Even under optimal conditions, virus yields were low and did not exceed 1 PFU per infected cell. Like other animal syncytium-forming 'foamy' viruses, the human virus induced both intranuclear and cytoplasmic antigens detectable by immmunofluorescence and was also markedly labile to freezing and thawing."}
{"id": "PMID:194866", "title": "Detection localization of Epstein-Barr virus-associated early antigens in single cells by autoradiography using 125I-labeled antibodies. (With 1 color plate).", "content": "A characteristic feature of virus-transformed cells is the expression of virus-specific antigens usually detectable by immunological or radioimmune procedures. We report here an autoradiographic method for the detection and localization of such antigens in individual cells which combines the cellular specificity and radiolabeling sensitivity of the above procedures. As a test system we have studied the reaction between virus antigen in some Epstein-Barr virus (EBV) DNA-containing cell lines and anti-virus antibody specificities in certain human sera. EBV DNA-containing cell lines express an EBV-determined nuclear antigen (EBNA) and some lines also express the EBV-associated antigens, early antigen (EA) and virus capsid antigen (VCA), in a minority of cells in the population. By employing appropriate 125I-IgG-labeled human sera, we clearly show that EA can be detected without difficulty in cell lines known to spontaneously express this antigen. Moreover, the specificity and sensitivity of the present method is such that low levels of EA cand be detected at cellular concentrations which remain undetectable by conventional immunofluorescence.", "contents": "Detection localization of Epstein-Barr virus-associated early antigens in single cells by autoradiography using 125I-labeled antibodies. (With 1 color plate). A characteristic feature of virus-transformed cells is the expression of virus-specific antigens usually detectable by immunological or radioimmune procedures. We report here an autoradiographic method for the detection and localization of such antigens in individual cells which combines the cellular specificity and radiolabeling sensitivity of the above procedures. As a test system we have studied the reaction between virus antigen in some Epstein-Barr virus (EBV) DNA-containing cell lines and anti-virus antibody specificities in certain human sera. EBV DNA-containing cell lines express an EBV-determined nuclear antigen (EBNA) and some lines also express the EBV-associated antigens, early antigen (EA) and virus capsid antigen (VCA), in a minority of cells in the population. By employing appropriate 125I-IgG-labeled human sera, we clearly show that EA can be detected without difficulty in cell lines known to spontaneously express this antigen. Moreover, the specificity and sensitivity of the present method is such that low levels of EA cand be detected at cellular concentrations which remain undetectable by conventional immunofluorescence."}
{"id": "PMID:194867", "title": "Transforming activity and antigenicity of an Epstein-Barr-like virus from lymphoblastoid cell lines of baboons with lymphoid disease.", "content": "Two lymphoblastoid cell lines were established from baboons with lymphoid disease. Cells of these lines were positive for complement and Fc receptors but lacked sheep cell receptors, theraby indicating B-cell origin. The cells contained antigens which cross-reacted with Epstein-Barr virus (EBV), viral capsid antigen (VCA), early antigen (EA) and membrane antigen (MA). Both lines released virus with in vitro transforming activity for lymphocytes of several primate species including humans. Cells of the original lines and transformed cells showed no staining for EB nuclear antigen (EBNA). The virus was neutralized by anti-MA positive baboon and human sera. Baboon virus and EBV had different but overlapping in vitro host-cell ranges.", "contents": "Transforming activity and antigenicity of an Epstein-Barr-like virus from lymphoblastoid cell lines of baboons with lymphoid disease. Two lymphoblastoid cell lines were established from baboons with lymphoid disease. Cells of these lines were positive for complement and Fc receptors but lacked sheep cell receptors, theraby indicating B-cell origin. The cells contained antigens which cross-reacted with Epstein-Barr virus (EBV), viral capsid antigen (VCA), early antigen (EA) and membrane antigen (MA). Both lines released virus with in vitro transforming activity for lymphocytes of several primate species including humans. Cells of the original lines and transformed cells showed no staining for EB nuclear antigen (EBNA). The virus was neutralized by anti-MA positive baboon and human sera. Baboon virus and EBV had different but overlapping in vitro host-cell ranges."}
{"id": "PMID:194868", "title": "Bovine type II interferon: activity in heterologous cells.", "content": "The antiviral and cell growth inhibition spectra of bovine and human interferons are described. The antiviral activity of type II interferon in heterologous cells far exceeded that of the corresponding type I interferon. Antiviral activity of bovine type II interferon parallels cell growth inhibition activity both in thermal inactivation kinetics as well as in the rate of synthesis. Furthermore, the spectrum of antiviral activity against heterologous cells was the same as that seen for cell growth inhibition suggesting that one molecule may mediate both effects. The therapeutic implications of type II interferon prepared in animals for use in human medicine are discussed briefly.", "contents": "Bovine type II interferon: activity in heterologous cells. The antiviral and cell growth inhibition spectra of bovine and human interferons are described. The antiviral activity of type II interferon in heterologous cells far exceeded that of the corresponding type I interferon. Antiviral activity of bovine type II interferon parallels cell growth inhibition activity both in thermal inactivation kinetics as well as in the rate of synthesis. Furthermore, the spectrum of antiviral activity against heterologous cells was the same as that seen for cell growth inhibition suggesting that one molecule may mediate both effects. The therapeutic implications of type II interferon prepared in animals for use in human medicine are discussed briefly."}
{"id": "PMID:194869", "title": "Immune deficiency of T system with possible T cell regulatory activity defect.", "content": "The occurrence of T system immunodeficiency in an infant together with excessive production of IgM and, to a lesser degree, of IgG and IgA, is an unusual combination. A case is reported in which an unremitting lung infection with lymphadenopathy and hepatosplenomegaly developed in a previously healthy two-month-old infant. Leukocytosis with lymphocytosis, monocytosis and eosinophilia was rapidly followed by leukopenia and lymphocytepenia after a blood transfusion for anemia. There was a transient clinical remission, but on relapse 10 days later, quantitative and functional T cell deficiency was found together with increased IgG and IgA and with IgM values reaching 50 times greater than normal. Thymic humoral factor was successful in vitro in increasing the number of identifiable T cells (E rosetts) as well as T cell function (leukocyte migration inhibition factor production). However, the infant died suddenly, and at autopsy evidence of a generalized inflammatory reaction compatible with a viral infection was found. The thymus was small, hypoplastic and hypocellular. It is speculated that the T system deficiency may have been acquired following Epstein-Barr virus infection, and that T cell regulatory activity of immunoglobulin production was defective.", "contents": "Immune deficiency of T system with possible T cell regulatory activity defect. The occurrence of T system immunodeficiency in an infant together with excessive production of IgM and, to a lesser degree, of IgG and IgA, is an unusual combination. A case is reported in which an unremitting lung infection with lymphadenopathy and hepatosplenomegaly developed in a previously healthy two-month-old infant. Leukocytosis with lymphocytosis, monocytosis and eosinophilia was rapidly followed by leukopenia and lymphocytepenia after a blood transfusion for anemia. There was a transient clinical remission, but on relapse 10 days later, quantitative and functional T cell deficiency was found together with increased IgG and IgA and with IgM values reaching 50 times greater than normal. Thymic humoral factor was successful in vitro in increasing the number of identifiable T cells (E rosetts) as well as T cell function (leukocyte migration inhibition factor production). However, the infant died suddenly, and at autopsy evidence of a generalized inflammatory reaction compatible with a viral infection was found. The thymus was small, hypoplastic and hypocellular. It is speculated that the T system deficiency may have been acquired following Epstein-Barr virus infection, and that T cell regulatory activity of immunoglobulin production was defective."}
{"id": "PMID:194871", "title": "[Psoriasis: A general disease? Can psoriasis be explained biochemically?].", "content": "The biochemical problems of psoriasis are discussed, especially two modern hypothesis about the pathogenesis of this skin disease. 1. DHEA-deficiency leading to an increase of G-6-PDH inaugurated by Holzmann et al. 2. cAMP deficiency in psoriatic lesions as a cause of psoriasis hypothized by Voorhees and Duell. A synopsis of the physiology of the steroid hormone DHEA (synthesis, regulation, conjugation and excretion) is given. There are doubts that this hypothesis is correct. Recent findings have indicated, that there is no decrease of cAMP in the psoriatic lesion--in contrast there is an increase of this cyclic nucleotid. It means that this theory is also doubtfull. Treatment of an hypothetical decrease of cAMP by AMP is not possible, because this AMP will not penetrate in the cell and cannot be metabolized to cAMP.", "contents": "[Psoriasis: A general disease? Can psoriasis be explained biochemically?]. The biochemical problems of psoriasis are discussed, especially two modern hypothesis about the pathogenesis of this skin disease. 1. DHEA-deficiency leading to an increase of G-6-PDH inaugurated by Holzmann et al. 2. cAMP deficiency in psoriatic lesions as a cause of psoriasis hypothized by Voorhees and Duell. A synopsis of the physiology of the steroid hormone DHEA (synthesis, regulation, conjugation and excretion) is given. There are doubts that this hypothesis is correct. Recent findings have indicated, that there is no decrease of cAMP in the psoriatic lesion--in contrast there is an increase of this cyclic nucleotid. It means that this theory is also doubtfull. Treatment of an hypothetical decrease of cAMP by AMP is not possible, because this AMP will not penetrate in the cell and cannot be metabolized to cAMP."}
{"id": "PMID:194872", "title": "[Staphylodermia superficialis circinata. The 5th obligatory cutaneous paraneoplasia].", "content": "Clinical observations on two cases of staphylodermia superficialis circinata are reported. This rare variation of superificial staphylococcal skin infection is identical with the \"erythema necroticans migrans\". As this cutaneous manifestation is highly associated with malignant internal diseases it must be regarded as a \"cutaneous paraneoplasia\". Out of 14 cases of erythema necroticans migrans, so far published this dermatosis occured in 13 patients suffering from pancreatic cancer. Association with pancreatitis was demonstrated in one case. In both cases herein reported the cutaneous manifestations were associated with a carcinoma of the pancreas and with cervix cancer. Extreme loss of weight, atrophic glossitis, therapy-resistant anemia and a slight diabetes are extra-cutaneous symptoms of this paraneoplastic syndrom.", "contents": "[Staphylodermia superficialis circinata. The 5th obligatory cutaneous paraneoplasia]. Clinical observations on two cases of staphylodermia superficialis circinata are reported. This rare variation of superificial staphylococcal skin infection is identical with the \"erythema necroticans migrans\". As this cutaneous manifestation is highly associated with malignant internal diseases it must be regarded as a \"cutaneous paraneoplasia\". Out of 14 cases of erythema necroticans migrans, so far published this dermatosis occured in 13 patients suffering from pancreatic cancer. Association with pancreatitis was demonstrated in one case. In both cases herein reported the cutaneous manifestations were associated with a carcinoma of the pancreas and with cervix cancer. Extreme loss of weight, atrophic glossitis, therapy-resistant anemia and a slight diabetes are extra-cutaneous symptoms of this paraneoplastic syndrom."}
{"id": "PMID:194873", "title": "[X-ray irradiation of dermatoses in the genital area].", "content": "Report on empirical data of X-ray treatment of dermatoses in the genital area, concerning indications, technique and results. Irradiations are mainly successful in large patches of Bowen's disease and Bowen's carcinoma as well as in Queyrat's erythroplasia and Paget's disease. Carcinomata of the penis should not exceed the stages T1-T2. Regression of Peyronie's disease is accelerated. Psoriatic lesions disappear following Grenz-rays without further topical treatment. Grenz-rays can also prevent or delay local recurrences of herpes simplex eruptions in the genital area.", "contents": "[X-ray irradiation of dermatoses in the genital area]. Report on empirical data of X-ray treatment of dermatoses in the genital area, concerning indications, technique and results. Irradiations are mainly successful in large patches of Bowen's disease and Bowen's carcinoma as well as in Queyrat's erythroplasia and Paget's disease. Carcinomata of the penis should not exceed the stages T1-T2. Regression of Peyronie's disease is accelerated. Psoriatic lesions disappear following Grenz-rays without further topical treatment. Grenz-rays can also prevent or delay local recurrences of herpes simplex eruptions in the genital area."}
{"id": "PMID:194875", "title": "Evaluation by electron microscopy of the integrity of iodinated plasmalipoproteins.", "content": "Iodination of proteins and lipoproteins is a widely used \"in vitro\" labelling procedure in metabolic, autoradiographic and various other studies. However, all available iodination techniques have involved the possible damage to the proteins by self-irradiation, oxidizing agents, the alkaline milieu or by the introduction of iodine into the molecular structure itself. To evaluate the integrity of iodinated lipoprotiens, we observed the electron microscopic appearance of normal and iodinated rabbit very low density lipoproteins (VLDL) by negative staining with phosphotungstic acid. Iodination up to a molar iodine/protein ratio of 2.89 did not results in any change of shape, size or aggregating tendency of the particles. No stacks or disk-like particles like those of various hyperlipoproteinemic states were found. We conclude that electron microscopy is a valuable tool in assessing the morphological appearance of lipoprotein iodination, but it should be complemented by other techniques.", "contents": "Evaluation by electron microscopy of the integrity of iodinated plasmalipoproteins. Iodination of proteins and lipoproteins is a widely used \"in vitro\" labelling procedure in metabolic, autoradiographic and various other studies. However, all available iodination techniques have involved the possible damage to the proteins by self-irradiation, oxidizing agents, the alkaline milieu or by the introduction of iodine into the molecular structure itself. To evaluate the integrity of iodinated lipoprotiens, we observed the electron microscopic appearance of normal and iodinated rabbit very low density lipoproteins (VLDL) by negative staining with phosphotungstic acid. Iodination up to a molar iodine/protein ratio of 2.89 did not results in any change of shape, size or aggregating tendency of the particles. No stacks or disk-like particles like those of various hyperlipoproteinemic states were found. We conclude that electron microscopy is a valuable tool in assessing the morphological appearance of lipoprotein iodination, but it should be complemented by other techniques."}
{"id": "PMID:194874", "title": "Effects of picric acid-formaldehyde fixation on the LH(HCG) receptors' binding activity in the rat testis. A histochemichal model for qualitative and quantitative studies.", "content": "PAF (picric acid-formaldehyde) fixation of rat testis for a short time at 0-4 degrees C was found to give satisfactory histological results and to preserve most of the specific binding activity of LH(HCG) receptors. Investigations of the characteristics of the hormone-receptor reaction after mild PAF fixation indicated that this reaction was not substantially affected in hormne receptor affinity and its own specificity; only the capacity of the receptors was lowered by about 20%. A histochemical model is presented whose main features are: fixation of testis tissue in PAF; freezing in liquid nitrogen and cutting in the cryostat; radiolabelled hormone-receptor binding reaction performed on the sections; autoradiography to reveal the binding reaction. The utility of the method for qualitative and quantitative receptor studies and its possible application to biopsy and surgical specimens, are discussed.", "contents": "Effects of picric acid-formaldehyde fixation on the LH(HCG) receptors' binding activity in the rat testis. A histochemichal model for qualitative and quantitative studies. PAF (picric acid-formaldehyde) fixation of rat testis for a short time at 0-4 degrees C was found to give satisfactory histological results and to preserve most of the specific binding activity of LH(HCG) receptors. Investigations of the characteristics of the hormone-receptor reaction after mild PAF fixation indicated that this reaction was not substantially affected in hormne receptor affinity and its own specificity; only the capacity of the receptors was lowered by about 20%. A histochemical model is presented whose main features are: fixation of testis tissue in PAF; freezing in liquid nitrogen and cutting in the cryostat; radiolabelled hormone-receptor binding reaction performed on the sections; autoradiography to reveal the binding reaction. The utility of the method for qualitative and quantitative receptor studies and its possible application to biopsy and surgical specimens, are discussed."}
{"id": "PMID:194879", "title": "Incidence of minor physical anomaly in autism.", "content": "Children diagnosed as autistic were matched by age and sex with 74 control subjects and examined for presence of minor physical anomalies. Of the 16 anomalies scored, autistic children demonstrated a significant accumulation greater than the number exhibited by normal children. Three of the stigmata--low seating of ears, hypertelorism, and syndactylia--were expressed differentially in the two groups, and high palate as well as unusual cranial circumference were significantly high in both groups. Clusters of stigmata that might be associated with known chromosomal disorders could not be identified. The increased number of anomalies suggests that among autistic children such congenital markers indicate a deviant intrauterine experience.", "contents": "Incidence of minor physical anomaly in autism. Children diagnosed as autistic were matched by age and sex with 74 control subjects and examined for presence of minor physical anomalies. Of the 16 anomalies scored, autistic children demonstrated a significant accumulation greater than the number exhibited by normal children. Three of the stigmata--low seating of ears, hypertelorism, and syndactylia--were expressed differentially in the two groups, and high palate as well as unusual cranial circumference were significantly high in both groups. Clusters of stigmata that might be associated with known chromosomal disorders could not be identified. The increased number of anomalies suggests that among autistic children such congenital markers indicate a deviant intrauterine experience."}
{"id": "PMID:194880", "title": "Phototaxis and membrane potential in the photosynthetic bacterium Rhodospirillum rubrum.", "content": "Cells of the photosynthetic bacterium Rhodospirillum rubrum cultivated anaerobically in light show phototaxis. The behavior of individual cells in response to the phenomenon is reversal(s) of the swimming direction when the intensity of the light available to them abruptly decreases. The tactic response was inhibited by antimycin, an inhibitor of the photosynthetic electron transfer system. The inhibitory effect of antimycin was overcome by phenazine methosulfate. Motility of the cells was not impaired by antimycin under aerobic conditions. Valinomycin plus potassium also inhibited their phototactic response; however, valinomycin or potassium alone had no effect. A change in membrane potential of the cells was measured as an absorbance change of carotenoid. Changes in the membrane potential caused by \"on-off\" light were prevented by antimycin and by valinomycin plus potassium, but not by antimycin plus phenazine methosulfate nor valinomycin or potassium alone. The results indicated that the phototactic response of R. rubrum is mediated by a sudden change in electron flow in the photosynthetic electron transfer system, and that the membrane potential plays an important role in manifestation of the response.", "contents": "Phototaxis and membrane potential in the photosynthetic bacterium Rhodospirillum rubrum. Cells of the photosynthetic bacterium Rhodospirillum rubrum cultivated anaerobically in light show phototaxis. The behavior of individual cells in response to the phenomenon is reversal(s) of the swimming direction when the intensity of the light available to them abruptly decreases. The tactic response was inhibited by antimycin, an inhibitor of the photosynthetic electron transfer system. The inhibitory effect of antimycin was overcome by phenazine methosulfate. Motility of the cells was not impaired by antimycin under aerobic conditions. Valinomycin plus potassium also inhibited their phototactic response; however, valinomycin or potassium alone had no effect. A change in membrane potential of the cells was measured as an absorbance change of carotenoid. Changes in the membrane potential caused by \"on-off\" light were prevented by antimycin and by valinomycin plus potassium, but not by antimycin plus phenazine methosulfate nor valinomycin or potassium alone. The results indicated that the phototactic response of R. rubrum is mediated by a sudden change in electron flow in the photosynthetic electron transfer system, and that the membrane potential plays an important role in manifestation of the response."}
{"id": "PMID:194881", "title": "On the role of the tubulin nonexchangeable GTP site in bovine neurotubule assembly.", "content": "A procedure for radiolabeling the terminal phosphoryl group of the tubulin nonexchangeable GTP site using bacterial acetate kinase and acetyl-32P is described. Warming such samples to 37 degrees results in microtubule assembly and  hydrolysis of the nonexchangeable site GTP in a parallel fashion. Removal of the microtubule-associated protein fraction from lebeled tubulin prevents hydrolysis and assembly, and recombination of these components restores both processes again in a parallel fashion. These and other experiments indicate that the nonexchangeable site GTP hydrolysis and assembly are intimately linked. The experiments also demonstrate that GRP is not required at the exchangeable nucleotide site for assembly to occur.", "contents": "On the role of the tubulin nonexchangeable GTP site in bovine neurotubule assembly. A procedure for radiolabeling the terminal phosphoryl group of the tubulin nonexchangeable GTP site using bacterial acetate kinase and acetyl-32P is described. Warming such samples to 37 degrees results in microtubule assembly and  hydrolysis of the nonexchangeable site GTP in a parallel fashion. Removal of the microtubule-associated protein fraction from lebeled tubulin prevents hydrolysis and assembly, and recombination of these components restores both processes again in a parallel fashion. These and other experiments indicate that the nonexchangeable site GTP hydrolysis and assembly are intimately linked. The experiments also demonstrate that GRP is not required at the exchangeable nucleotide site for assembly to occur."}
{"id": "PMID:194885", "title": "Tuna cytochrome c at 2.0 A resolution. III. Coordinate optimization and comparison of structures.", "content": "Optimum coordinate sets have been obtained for ferrocytochrome c and the two symmetry-independent molecules of ferricytochrome c from tuna at 2.0 A resolution by making the best fit of models with standard bond lengths and angles to the experimental electron density maps (1977) J. Biol. Chem. 252, 759-785, as a preliminary to full refinement with 1.5 A data. Both the Diamond model-building programs and locally developed minicomputer routines were tried, with the latter preferred for economy and ease of operation, although both gave satisfactory results. Atomic coordinates are available on microfiche or from the Brookhaven Protein Data Bank. Using the two ferricytochrome molecules as a control, no differences between oxidized and reduced cytochrome molecules can be seen that are outside the probable limits of accuracy of the 2.0 A analysis. Rotation and subtractive difference map comparisons also show no conformation changes. If believable differences do appear in the course of the 1.5 A refinement now underway, these should be no more than minor breathing of main chain or adjustment of side chains.", "contents": "Tuna cytochrome c at 2.0 A resolution. III. Coordinate optimization and comparison of structures. Optimum coordinate sets have been obtained for ferrocytochrome c and the two symmetry-independent molecules of ferricytochrome c from tuna at 2.0 A resolution by making the best fit of models with standard bond lengths and angles to the experimental electron density maps (1977) J. Biol. Chem. 252, 759-785, as a preliminary to full refinement with 1.5 A data. Both the Diamond model-building programs and locally developed minicomputer routines were tried, with the latter preferred for economy and ease of operation, although both gave satisfactory results. Atomic coordinates are available on microfiche or from the Brookhaven Protein Data Bank. Using the two ferricytochrome molecules as a control, no differences between oxidized and reduced cytochrome molecules can be seen that are outside the probable limits of accuracy of the 2.0 A analysis. Rotation and subtractive difference map comparisons also show no conformation changes. If believable differences do appear in the course of the 1.5 A refinement now underway, these should be no more than minor breathing of main chain or adjustment of side chains."}
{"id": "PMID:194893", "title": "Glycosaminoglycan synthesis by cultured human skin fibroblasts after transformation with simian virus 40.", "content": "The synthesis of glycosaminoglycans by human skin fibroblasts derived from normal subjects, Hurler and Marfan patients before and after transformation by SV40 virus has been studied. Virus transformation results in a marked increase in hyaluronic acid synthesis in normal and Hurler fibroblasts and, to a lesser extent, in Marfan fibroblasts which show augmented synthesis of this polysaccharide before transformation. There is also an increase in heparan sulfate synthesis but a moderate decrease in dermatan sulfate synthesis on transformation. Incubation of transformed fibroblasts with 4-methylumbelliferyl-beta-D-xyloside results in a marked increase in synthesis of free chondroitin sulfate chains. The synthesis of hyaluronic acid, but not of dermatan sulfate, is inversely proportional to cell density in normal fibroblasts but not in transformed fibroblasts.", "contents": "Glycosaminoglycan synthesis by cultured human skin fibroblasts after transformation with simian virus 40. The synthesis of glycosaminoglycans by human skin fibroblasts derived from normal subjects, Hurler and Marfan patients before and after transformation by SV40 virus has been studied. Virus transformation results in a marked increase in hyaluronic acid synthesis in normal and Hurler fibroblasts and, to a lesser extent, in Marfan fibroblasts which show augmented synthesis of this polysaccharide before transformation. There is also an increase in heparan sulfate synthesis but a moderate decrease in dermatan sulfate synthesis on transformation. Incubation of transformed fibroblasts with 4-methylumbelliferyl-beta-D-xyloside results in a marked increase in synthesis of free chondroitin sulfate chains. The synthesis of hyaluronic acid, but not of dermatan sulfate, is inversely proportional to cell density in normal fibroblasts but not in transformed fibroblasts."}
{"id": "PMID:194898", "title": "Cyclic 3':5'-nucleotide phosphodiesterase. Stimulation of bovine brain cytoplasmic enzyme by lysophosphatidylcholine.", "content": "Brain cytoplasmic cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.17) requires an endogenous Ca2+-binding protein for ful activity. We now show that lysophosphatidylcholine also effectively enhances activator-deficient phosphodiesterase activity. Stimulation by both ligands was immediate and reversible; both rendered the enzyme more thermally labile, decreased the energy of activation, and increased the Vmax of phosphodiesterase without affecting its apparent Km for adenosine 3'5'-monophosphate. However, the cofactor requirements of the two ligands were different. Although the protein activator gave a greater stimulation than lysophosphatidylcholine, the simultaneous presence of the two gave a stimulation comparable to lysophosphatidylcholine, suggesting that the effect of the latter was predominant. Phosphodiesterase was also stimulated by oleic acid, cardiolipin, and phosphatidylinositol, albeit to a less extent.", "contents": "Cyclic 3':5'-nucleotide phosphodiesterase. Stimulation of bovine brain cytoplasmic enzyme by lysophosphatidylcholine. Brain cytoplasmic cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.17) requires an endogenous Ca2+-binding protein for ful activity. We now show that lysophosphatidylcholine also effectively enhances activator-deficient phosphodiesterase activity. Stimulation by both ligands was immediate and reversible; both rendered the enzyme more thermally labile, decreased the energy of activation, and increased the Vmax of phosphodiesterase without affecting its apparent Km for adenosine 3'5'-monophosphate. However, the cofactor requirements of the two ligands were different. Although the protein activator gave a greater stimulation than lysophosphatidylcholine, the simultaneous presence of the two gave a stimulation comparable to lysophosphatidylcholine, suggesting that the effect of the latter was predominant. Phosphodiesterase was also stimulated by oleic acid, cardiolipin, and phosphatidylinositol, albeit to a less extent."}
{"id": "PMID:194900", "title": "Use of N-chlorosuccinimide/urea for the selective cleavage of tryptophanyl peptide bonds in proteins. Cytochrome c.", "content": "The conditions and utility of the N-chlorosuccinimide/urea (NCS/urea) reagent for the selective cleavage of tryptophanyl peptide bonds in proteins is demonstrated with cytochrome c. At low concentrations of NCS/urea the oxidation of thioether side chains in cytochrome c is the predominant reaction. Methionyl residues are oxidized to sulfoxide and the heme-thioether bridge is partially cleaved. At 10-fold excess of NCS/urea reagent, cleavage of the tryptophanyl peptide bond is optimal at approximately 50% yield in several species of cytochrome c studied. Analytical data on isolated horse cytochrome c peptide fragments demonstrate lack of modification and cleavage at tyrosyl and histidyl residues. However, at high concentrations of NCS/urea reagent (30-fold) unexpected conversions of methionine to sulfone and cysteine to cysteic acid in intact proteins are observed. This is in contradistinction to the absence of sulfone in NCS/urea-reacted amino acid mixtures. The mechanisms of halogenation and cleavage by N-bromosuccinimide, N-iodosuccinimide, and N-chlorosuccinimide are discussed. It is porposed that the selectivity with respect to halogenation by N-chlorosuccinimide is due to the insignificant participation of molecular chlorine in the NCS/urea reaction. A mechanism of halogenation and cleavage by NCS at tryptophan is also offered.", "contents": "Use of N-chlorosuccinimide/urea for the selective cleavage of tryptophanyl peptide bonds in proteins. Cytochrome c. The conditions and utility of the N-chlorosuccinimide/urea (NCS/urea) reagent for the selective cleavage of tryptophanyl peptide bonds in proteins is demonstrated with cytochrome c. At low concentrations of NCS/urea the oxidation of thioether side chains in cytochrome c is the predominant reaction. Methionyl residues are oxidized to sulfoxide and the heme-thioether bridge is partially cleaved. At 10-fold excess of NCS/urea reagent, cleavage of the tryptophanyl peptide bond is optimal at approximately 50% yield in several species of cytochrome c studied. Analytical data on isolated horse cytochrome c peptide fragments demonstrate lack of modification and cleavage at tyrosyl and histidyl residues. However, at high concentrations of NCS/urea reagent (30-fold) unexpected conversions of methionine to sulfone and cysteine to cysteic acid in intact proteins are observed. This is in contradistinction to the absence of sulfone in NCS/urea-reacted amino acid mixtures. The mechanisms of halogenation and cleavage by N-bromosuccinimide, N-iodosuccinimide, and N-chlorosuccinimide are discussed. It is porposed that the selectivity with respect to halogenation by N-chlorosuccinimide is due to the insignificant participation of molecular chlorine in the NCS/urea reaction. A mechanism of halogenation and cleavage by NCS at tryptophan is also offered."}
{"id": "PMID:194902", "title": "Studies on a defective variant of simian virus 40 that is substituted with DNA sequences derived from monkey. II. Structure of DNA.", "content": "The structure of a substituted, reiterated defective variant of the simian virus 40 genome has been analyzed. The DNA of the defective variant is a closed circular duplex resistant to restriction endonuclease R-EcoRI and slightly shorter than the genome of wild type simian virus 40. Analysis of the double-stranded DNA segments produced by the action of a variety of restriction endonucleases on the defective genome allow description of the molecule as follows. (a) The full DNA molecule contains four tandem repeats of a DNA segment containing both SV40 and monkey DNA sequences. (b) Three out of the four segments are identical and are about 23% of the wild type genome in length: one segment of the four is larger and contains an additional peice of DNA about 4.3% of a wild type genome in length, but is otherwise identical with the other three segments. (c) Portions of the defective variant that contain monkey DNA can be isolated as discrete segments by restriction endonuclease digestion. (d) Some of the sequences originating from monkey DNA are derived from the highly reiterated class of monkey DNA sequences; others may represent sequences derived from infrequently reiterated or single copy monkey sequences.", "contents": "Studies on a defective variant of simian virus 40 that is substituted with DNA sequences derived from monkey. II. Structure of DNA. The structure of a substituted, reiterated defective variant of the simian virus 40 genome has been analyzed. The DNA of the defective variant is a closed circular duplex resistant to restriction endonuclease R-EcoRI and slightly shorter than the genome of wild type simian virus 40. Analysis of the double-stranded DNA segments produced by the action of a variety of restriction endonucleases on the defective genome allow description of the molecule as follows. (a) The full DNA molecule contains four tandem repeats of a DNA segment containing both SV40 and monkey DNA sequences. (b) Three out of the four segments are identical and are about 23% of the wild type genome in length: one segment of the four is larger and contains an additional peice of DNA about 4.3% of a wild type genome in length, but is otherwise identical with the other three segments. (c) Portions of the defective variant that contain monkey DNA can be isolated as discrete segments by restriction endonuclease digestion. (d) Some of the sequences originating from monkey DNA are derived from the highly reiterated class of monkey DNA sequences; others may represent sequences derived from infrequently reiterated or single copy monkey sequences."}
{"id": "PMID:194903", "title": "Adenosine 3':5'-monophosphate-regulated phosphoprotein system of neuronal membranes. I. Solubilization, purification, and some properties of an endogenous phosphoprotein.", "content": "An endogenous substrate for adenosine 3':5'-monophosphate-dependent protein kinase has been solubilized, and purified about 5,000-fold to apparent homogeneity, from a particulate fraction of bovine cerebral cortex enriched in synaptic membranes. This endogenous substrate, referred to as Protein I, is apparently specific to nervous tissue, and is composed of two types of polypeptides, present in a proportion of 1 (Protein Ia, 86,000 daltons) to 2 (Protein Ib, 80,000 daltons). In the presence of cAMP-dependent Protein I kinase purified from the same membrane fractions, Proteins Ia and Ib incorporated 0.83 and 0.81 mol of phosphate into serine/mol of peptide, respectively. Proteins Ia and Ib have similar amino acid compositions and have isoelectric points of 10.3 and 10.2, respectively. Both types of polypeptide have a relatively high content of glycine and proline, and both are degraded to a peptide of 48,000 daltons by highly purified collagenase, suggesting that Proteins Ia and Ib contain some sequences similar to those observed in collagen. The sedimentation coefficient of Protein Ia and Protein Ib was determined to be 2.9 S. The data suggest that both Protein Ia and Protein Ib have an elongated shape.", "contents": "Adenosine 3':5'-monophosphate-regulated phosphoprotein system of neuronal membranes. I. Solubilization, purification, and some properties of an endogenous phosphoprotein. An endogenous substrate for adenosine 3':5'-monophosphate-dependent protein kinase has been solubilized, and purified about 5,000-fold to apparent homogeneity, from a particulate fraction of bovine cerebral cortex enriched in synaptic membranes. This endogenous substrate, referred to as Protein I, is apparently specific to nervous tissue, and is composed of two types of polypeptides, present in a proportion of 1 (Protein Ia, 86,000 daltons) to 2 (Protein Ib, 80,000 daltons). In the presence of cAMP-dependent Protein I kinase purified from the same membrane fractions, Proteins Ia and Ib incorporated 0.83 and 0.81 mol of phosphate into serine/mol of peptide, respectively. Proteins Ia and Ib have similar amino acid compositions and have isoelectric points of 10.3 and 10.2, respectively. Both types of polypeptide have a relatively high content of glycine and proline, and both are degraded to a peptide of 48,000 daltons by highly purified collagenase, suggesting that Proteins Ia and Ib contain some sequences similar to those observed in collagen. The sedimentation coefficient of Protein Ia and Protein Ib was determined to be 2.9 S. The data suggest that both Protein Ia and Protein Ib have an elongated shape."}
{"id": "PMID:194904", "title": "On the mechanism of ATP-induced shape changes in human erythrocyte membranes. II. The role of ATP.", "content": "In the preceding paper (Sheetz, M. and S.J. Singer. 1977. J Cell Biol. 73:638-646) it was shown that erythrocyte ghosts undergo pronounced shape changes in the presence of mg-ATP. The biochemical effects of the action of ATP are herein examined. The biochemical effects of the action of ATP are herein examined. Phosphorylation by ATP of spectrin component 2 of the erythrocyte membrane is known to occur. We have shown that it is only membrane protein that is significantly phosphorylated under the conditions where the shape changes are produced. The extent of this phosphorylation rises with increasing ATP concentration, reaching nearly 1 mol phosphoryle group per mole of component 2 at 8mM ATP. Most of this phosphorylation appears to occur at a single site on the protein molecule, according to cyanogen bromide peptide cleavage experiments. The degree of phosphorylation of component 2 is apparently also regulated by a membrane-bound protein phosphatase. This activity can be demonstrated in erythrocyte ghosts prepared from intact cells prelabeled with [(32)P]phosphate. In addition to the phosphorylation of component 2, some phosphorylation of lipids, mainly of phosphatidylinositol, is also known to occur. The ghost shape changes are, however, shown to be correlated with the degree of phosphorylation of component 2. In such experiment, the incorporation of exogenous phosphatases into ghosts reversed the shape changes produced by ATP, or by the membrane-intercalating drug chlorpromazine. The results obtained in this and the preceding paper are consistent with the proposal that the erythrocyte membrane possesses kinase and phosphates activities which produce phosphorylation and dephosphorylation of a specific site on spectrin component 2 molecules; the steady-state level of this phosphorylation regulates the structural state of the spectrin complex on the cytoplasmic surface of the membrane, which in turn exerts an important control on the shape of the cell.", "contents": "On the mechanism of ATP-induced shape changes in human erythrocyte membranes. II. The role of ATP. In the preceding paper (Sheetz, M. and S.J. Singer. 1977. J Cell Biol. 73:638-646) it was shown that erythrocyte ghosts undergo pronounced shape changes in the presence of mg-ATP. The biochemical effects of the action of ATP are herein examined. The biochemical effects of the action of ATP are herein examined. Phosphorylation by ATP of spectrin component 2 of the erythrocyte membrane is known to occur. We have shown that it is only membrane protein that is significantly phosphorylated under the conditions where the shape changes are produced. The extent of this phosphorylation rises with increasing ATP concentration, reaching nearly 1 mol phosphoryle group per mole of component 2 at 8mM ATP. Most of this phosphorylation appears to occur at a single site on the protein molecule, according to cyanogen bromide peptide cleavage experiments. The degree of phosphorylation of component 2 is apparently also regulated by a membrane-bound protein phosphatase. This activity can be demonstrated in erythrocyte ghosts prepared from intact cells prelabeled with [(32)P]phosphate. In addition to the phosphorylation of component 2, some phosphorylation of lipids, mainly of phosphatidylinositol, is also known to occur. The ghost shape changes are, however, shown to be correlated with the degree of phosphorylation of component 2. In such experiment, the incorporation of exogenous phosphatases into ghosts reversed the shape changes produced by ATP, or by the membrane-intercalating drug chlorpromazine. The results obtained in this and the preceding paper are consistent with the proposal that the erythrocyte membrane possesses kinase and phosphates activities which produce phosphorylation and dephosphorylation of a specific site on spectrin component 2 molecules; the steady-state level of this phosphorylation regulates the structural state of the spectrin complex on the cytoplasmic surface of the membrane, which in turn exerts an important control on the shape of the cell."}
{"id": "PMID:194905", "title": "Metabolism of cationized lipoproteins by human fibroblasts. Biochemical and morphologic correlations.", "content": "Human plasma low density lipoprotein (LDL) that had been rendered polycationic by coupling with N, N-dimethyl-1, 3-propanediamine (DMPA) was shown by electron microscopy to bind in clusters to the surface of human fibroblasts. The clusters resembled those formed by polycationic ferritin (DMPA-feritin), a visual probe that binds to anionic site on the plasma membrane. Biochemical studies with (125)I-labeled DMPA-LDL showed that the membrane-bound lipoprotein was internalized and hydrolyzed in lysosomes. The turnover time for cell bound (125)I-DMPA-LDL, i.e., the time in which the amount of (125)I-DMPA-LDL degraded was equal to the steady-state cellular content of the lipoprotein, was about 50 h. Because the DMPA-LDL gained access to fibroblasts by binding nonspecifically to anionic sites on the cell surface rather than by binding to the physiologic LDL receptor, its uptake failed to be regulated under conditions in which the uptake of native LDL was reduced by feedback suppression of the LDL receptor. As a result, unlike the case with native LDL, the DMPA-LDL accumulated progressively within the cell, and this led to a massive increase in the cellular content of both free and esterified cholesterol. Studies with (14)C-oleate showed that at least 20 percent of the accumulated cholesteryl esters represented cholesterol that had been esterified within the cell. After 4 days of incubation with 10 mug/ml of DMPA-LDL, fibroblasts had accumulated so much cholesteryl ester that neutral lipid droplets were visible at the light microscope level with Oil Red O staining. By electron microscopy, these intracellular lipid droplets were observed to lack a tripartite limiting membrane. The ability to cause the overaccumulation of cholesteryl esters within cells by using DMPA-LDL provides a model system for study of the pathologic consequences at the cellular level of massive deposition of cholesteryl ester.", "contents": "Metabolism of cationized lipoproteins by human fibroblasts. Biochemical and morphologic correlations. Human plasma low density lipoprotein (LDL) that had been rendered polycationic by coupling with N, N-dimethyl-1, 3-propanediamine (DMPA) was shown by electron microscopy to bind in clusters to the surface of human fibroblasts. The clusters resembled those formed by polycationic ferritin (DMPA-feritin), a visual probe that binds to anionic site on the plasma membrane. Biochemical studies with (125)I-labeled DMPA-LDL showed that the membrane-bound lipoprotein was internalized and hydrolyzed in lysosomes. The turnover time for cell bound (125)I-DMPA-LDL, i.e., the time in which the amount of (125)I-DMPA-LDL degraded was equal to the steady-state cellular content of the lipoprotein, was about 50 h. Because the DMPA-LDL gained access to fibroblasts by binding nonspecifically to anionic sites on the cell surface rather than by binding to the physiologic LDL receptor, its uptake failed to be regulated under conditions in which the uptake of native LDL was reduced by feedback suppression of the LDL receptor. As a result, unlike the case with native LDL, the DMPA-LDL accumulated progressively within the cell, and this led to a massive increase in the cellular content of both free and esterified cholesterol. Studies with (14)C-oleate showed that at least 20 percent of the accumulated cholesteryl esters represented cholesterol that had been esterified within the cell. After 4 days of incubation with 10 mug/ml of DMPA-LDL, fibroblasts had accumulated so much cholesteryl ester that neutral lipid droplets were visible at the light microscope level with Oil Red O staining. By electron microscopy, these intracellular lipid droplets were observed to lack a tripartite limiting membrane. The ability to cause the overaccumulation of cholesteryl esters within cells by using DMPA-LDL provides a model system for study of the pathologic consequences at the cellular level of massive deposition of cholesteryl ester."}
{"id": "PMID:194906", "title": "The structure of postsynaptic densities isolated from dog cerebral cortex. I. Overall morphology and protein composition.", "content": "A postsynaptic density (PSD) fraction, including some adherent subsynaptic web material, has been isolated from dog cerebral cortex by a short-procedure modification of methods of Davis and Bloom (21, 22) and Cotman and Taylor (20), using Triton X-100. The fraction has been visualized by thin-section, replica, and negative (phosphotungstic acid) staining electron microscopy and its proteins separated by high-resoltuion SDS gel electrophoresis. Morphologically, the preparation seems to be quite pure, with very little membrane contamination. The density is composed of protein, no nuclei acids, and very little phospholipids being detectable. The fraction had no ATPase or GTPase activity, but it did have a very small amount of cytochrome c oxidase activity (of a specific activity less than 0.5 percent that of a mitochondrial fraction) and a small amount of 5'- nucleotidase activity (of a specific activity between 6 and 7 percent that of a synaptic membrane fraction). Electron micrographs reveal cup-shaped structures approximately 400nm long and approximately 40nm wide, made up of apparent particles 13-28nm in diameter. However, en face views, and particularly micrographs of replicas and PTA-stained preparations, reveal a disk-shaped structure, outside diameter approximately 400 nm, in which filaments are seen to extend from the central part of the density. High resolution gel electrophoresis studies indicated some 15 major proteins and perhaps 10 or more minor ones; the predominant protein had a mol wt of 51,000, followed by ones at 45,000, 40,000, 31,000, 26,000, and several at 100,000. A comparison by gel electrophoresis of density fraction proteins with those of a lysed synaptosomal membrane fraction containing some adherent densities indicated some comigrating proteins, but the major membrane fraction protein, mol wt 52,000, was not found in the density fraction. Antibodies raised against the density fraction reacted with a preparation of solubilized synaptic membrane proteins. By both these criteria, it was considered that the density and the synaptic membrane have some proteins in common. By separately mixing (125)I-labeled myelin, synaptic vesicle, and mitochondrial fraction proteins with synaptosomes, and then isolating the density fraction from the mixture, it was concluded that a major 26,000 mol wt density fraction protein was common to both mitochondria and density, that none of the proteins of the density were contaminants from the mitochondrial fraction, that a minor approximately 150,000 band was a contaminant from the synaptic vesicle fraction, and that the moderately staining PSD fraction protein of 17,000 mol wt band was the result of contamination by the major basic protein of myelin. On the basis of the marker enzymatic assays and the mixing experiments, it is considered that the density fraction is moderately pure biochemically, and that its protein composition, aside from a few exceptions noted above, reflects its in situ character.", "contents": "The structure of postsynaptic densities isolated from dog cerebral cortex. I. Overall morphology and protein composition. A postsynaptic density (PSD) fraction, including some adherent subsynaptic web material, has been isolated from dog cerebral cortex by a short-procedure modification of methods of Davis and Bloom (21, 22) and Cotman and Taylor (20), using Triton X-100. The fraction has been visualized by thin-section, replica, and negative (phosphotungstic acid) staining electron microscopy and its proteins separated by high-resoltuion SDS gel electrophoresis. Morphologically, the preparation seems to be quite pure, with very little membrane contamination. The density is composed of protein, no nuclei acids, and very little phospholipids being detectable. The fraction had no ATPase or GTPase activity, but it did have a very small amount of cytochrome c oxidase activity (of a specific activity less than 0.5 percent that of a mitochondrial fraction) and a small amount of 5'- nucleotidase activity (of a specific activity between 6 and 7 percent that of a synaptic membrane fraction). Electron micrographs reveal cup-shaped structures approximately 400nm long and approximately 40nm wide, made up of apparent particles 13-28nm in diameter. However, en face views, and particularly micrographs of replicas and PTA-stained preparations, reveal a disk-shaped structure, outside diameter approximately 400 nm, in which filaments are seen to extend from the central part of the density. High resolution gel electrophoresis studies indicated some 15 major proteins and perhaps 10 or more minor ones; the predominant protein had a mol wt of 51,000, followed by ones at 45,000, 40,000, 31,000, 26,000, and several at 100,000. A comparison by gel electrophoresis of density fraction proteins with those of a lysed synaptosomal membrane fraction containing some adherent densities indicated some comigrating proteins, but the major membrane fraction protein, mol wt 52,000, was not found in the density fraction. Antibodies raised against the density fraction reacted with a preparation of solubilized synaptic membrane proteins. By both these criteria, it was considered that the density and the synaptic membrane have some proteins in common. By separately mixing (125)I-labeled myelin, synaptic vesicle, and mitochondrial fraction proteins with synaptosomes, and then isolating the density fraction from the mixture, it was concluded that a major 26,000 mol wt density fraction protein was common to both mitochondria and density, that none of the proteins of the density were contaminants from the mitochondrial fraction, that a minor approximately 150,000 band was a contaminant from the synaptic vesicle fraction, and that the moderately staining PSD fraction protein of 17,000 mol wt band was the result of contamination by the major basic protein of myelin. On the basis of the marker enzymatic assays and the mixing experiments, it is considered that the density fraction is moderately pure biochemically, and that its protein composition, aside from a few exceptions noted above, reflects its in situ character."}
{"id": "PMID:194907", "title": "Studies on the mechanism for entry of vesicular stomatitis virus glycoprotein G mRNA into membrane-bound polyribosome complexes.", "content": "Glycoprotein mRNA (G mRNA) of vesicular stomatitis virus is synthesized in the cytosol fraction of infected HeLa cells. Shortly after synthesis, this mRNA associates with 40S ribosomal subunits and subsequently forms 80S monosomes in the cytosol fraction. The bulk of labeled G mRNA is then found in polysomes associated with the membrane, without first appearing in the subunit or monomer pool of the membrane-bound fraction. Inhibition of the initiation of protein synthesis by pactamycin or muconomycin A blocks entry of newly synthesized G m RNA into membrane-bound polysomes. Under these circumstances, labeled G mRNA accumulates into the cytosol. Inhibition of the elongation of protein synthesis by cucloheximide, however, allows entry of 60 percent of newly synthesized G mRNA into membrane-bound polysomes. Furthermore, prelabeled G mRNA associated with membrane-bound polysomes is released from the membrane fraction in vivo by pactamycin or mucomycon A and in vitro by 1mM puromycin - 0.5 M KCI. This release is not due to nonspecific effects of the drugs. These results demonstrate that association of G mRNA with membrane-bound polysomes is dependent upon polysome formation and initiation of protein synthesis. Therefore, direct association of the 3' end of G mRNA with the membrane does not appear to be the initial event in the formation of membrane-bound polysomes.", "contents": "Studies on the mechanism for entry of vesicular stomatitis virus glycoprotein G mRNA into membrane-bound polyribosome complexes. Glycoprotein mRNA (G mRNA) of vesicular stomatitis virus is synthesized in the cytosol fraction of infected HeLa cells. Shortly after synthesis, this mRNA associates with 40S ribosomal subunits and subsequently forms 80S monosomes in the cytosol fraction. The bulk of labeled G mRNA is then found in polysomes associated with the membrane, without first appearing in the subunit or monomer pool of the membrane-bound fraction. Inhibition of the initiation of protein synthesis by pactamycin or muconomycin A blocks entry of newly synthesized G m RNA into membrane-bound polysomes. Under these circumstances, labeled G mRNA accumulates into the cytosol. Inhibition of the elongation of protein synthesis by cucloheximide, however, allows entry of 60 percent of newly synthesized G mRNA into membrane-bound polysomes. Furthermore, prelabeled G mRNA associated with membrane-bound polysomes is released from the membrane fraction in vivo by pactamycin or mucomycon A and in vitro by 1mM puromycin - 0.5 M KCI. This release is not due to nonspecific effects of the drugs. These results demonstrate that association of G mRNA with membrane-bound polysomes is dependent upon polysome formation and initiation of protein synthesis. Therefore, direct association of the 3' end of G mRNA with the membrane does not appear to be the initial event in the formation of membrane-bound polysomes."}
{"id": "PMID:194908", "title": "Acute actions of 1,25-dihydroxy-vitamin D3 in normal man: effect on calcium and parathyroid status.", "content": "The present study was undertaken to evaluate the acute effect of 1,25-dihydroxy-vitamin D3 (1,25 (OH)2D3) on serum Ca, P and immunoreactive parathyroid (iPTH) and urinary Ca, P. and cyclic AMP. In 8 normal subjects, samples were collected over intervals of 30 to 60 min during a control day and on a treatment day following oral ingestion of 1,25(OH)2D3, 2.7 microgram. For the entire group there were no significant changes in serum Ca. P, iPTH or urinary P. Urinary Ca increased significantly 7 h after administration of 1,25(OH)2D3, and urinary cAMP decreased at 12 h. In 4 patients (group A). showing an increase in serum Ca by 0;2 to 0.4 mg/dl, serum iPTH decreased in 3, and the decrease in urinary cAMP appeared sooner. Among 4 patients showing no change in serum Ca after 1,25(HO)2D3 (group B), 3 showed an increase in iPTH. These data document the early onset of action of 1,25(OH)2D3 following its administration to normal man; increments in urinary Ca provide the most sensitive index of its action. The data provide no support for the view that 1,25(OH)2D3 exerts any direct inhibitory effect on the secretion of parathyroid hormone.", "contents": "Acute actions of 1,25-dihydroxy-vitamin D3 in normal man: effect on calcium and parathyroid status. The present study was undertaken to evaluate the acute effect of 1,25-dihydroxy-vitamin D3 (1,25 (OH)2D3) on serum Ca, P and immunoreactive parathyroid (iPTH) and urinary Ca, P. and cyclic AMP. In 8 normal subjects, samples were collected over intervals of 30 to 60 min during a control day and on a treatment day following oral ingestion of 1,25(OH)2D3, 2.7 microgram. For the entire group there were no significant changes in serum Ca. P, iPTH or urinary P. Urinary Ca increased significantly 7 h after administration of 1,25(OH)2D3, and urinary cAMP decreased at 12 h. In 4 patients (group A). showing an increase in serum Ca by 0;2 to 0.4 mg/dl, serum iPTH decreased in 3, and the decrease in urinary cAMP appeared sooner. Among 4 patients showing no change in serum Ca after 1,25(HO)2D3 (group B), 3 showed an increase in iPTH. These data document the early onset of action of 1,25(OH)2D3 following its administration to normal man; increments in urinary Ca provide the most sensitive index of its action. The data provide no support for the view that 1,25(OH)2D3 exerts any direct inhibitory effect on the secretion of parathyroid hormone."}
{"id": "PMID:194909", "title": "The effect of conjugated estrogens on the renin-angiotensin system.", "content": "In a survey of 3 California communities by the Stanford Heart Disease Prevention Program, we obtained data on blood pressure, medications, age, height and weight, blood for measurement of plasma renin activity (PRA), plasma renin concentration (PRC), plasma renin reactivity (RR), and plasma renin substate concentration (PRS), and urine for measurement of urinary sodium and creatinine. No effect of conjugated estrogens (Premarin) on blood pressure could be discerned when the blood pressure, corrected for age and relative weight, of 575 women on no medication was compared to that of 82 women taking only Premarin. Premarin increased PRA, PRS, and RR, but had no effect on PRC. We also found in both Premarin-treated woman and controls 1) that RR was positively correlated with PRS, and 2) that PRA is dependent on PRC and PRS. These data indicate that the reninrenin substrate reaction of plasma, even at normal substrate concentration, is strongly deprendent on PRS.", "contents": "The effect of conjugated estrogens on the renin-angiotensin system. In a survey of 3 California communities by the Stanford Heart Disease Prevention Program, we obtained data on blood pressure, medications, age, height and weight, blood for measurement of plasma renin activity (PRA), plasma renin concentration (PRC), plasma renin reactivity (RR), and plasma renin substate concentration (PRS), and urine for measurement of urinary sodium and creatinine. No effect of conjugated estrogens (Premarin) on blood pressure could be discerned when the blood pressure, corrected for age and relative weight, of 575 women on no medication was compared to that of 82 women taking only Premarin. Premarin increased PRA, PRS, and RR, but had no effect on PRC. We also found in both Premarin-treated woman and controls 1) that RR was positively correlated with PRS, and 2) that PRA is dependent on PRC and PRS. These data indicate that the reninrenin substrate reaction of plasma, even at normal substrate concentration, is strongly deprendent on PRS."}
{"id": "PMID:194910", "title": "Studies on phenolic steriods in human subjects. XXI. renal metabolism, conjugation and excretion of four androgens: a comparison with estriol.", "content": "The present study was conducted in order to ascertain whether the human kidney can conjugate androgens to an extent similar to that of estriol (E3). Differently labeled androgens (testosterone, DHT and androstenedione) were injected simultaneously into a peripheral vein and the renal artery. The excretion of the radioactivity in the early urine collections served as an index of the ability of the kidney to conjugate and/or metabolize the various steroids administered. It was shown that the human kidney can conjugate testosterone to some extent as the 17-glucuronide of DHT, but to a much lesser degree that E3. Androstenedione was not conjugated by the kidney and the excretion DHT was paradoxically lower following its renal artery administration than following its peripheral injection. We interpret the latter to indicate that some kidney cells may contain receptors with very high affinity for DHT, thus leading to the lower excretion observed. The administration of androstenediol (into the renal artery) and E3 (peripherally) indicated that the diol was not conjugated as readily as E3. The results point to the ability of the kidney to conjugate testosterone to some extent; however, in no case was it able to conjugate an androgen with the same facility as it does E3.", "contents": "Studies on phenolic steriods in human subjects. XXI. renal metabolism, conjugation and excretion of four androgens: a comparison with estriol. The present study was conducted in order to ascertain whether the human kidney can conjugate androgens to an extent similar to that of estriol (E3). Differently labeled androgens (testosterone, DHT and androstenedione) were injected simultaneously into a peripheral vein and the renal artery. The excretion of the radioactivity in the early urine collections served as an index of the ability of the kidney to conjugate and/or metabolize the various steroids administered. It was shown that the human kidney can conjugate testosterone to some extent as the 17-glucuronide of DHT, but to a much lesser degree that E3. Androstenedione was not conjugated by the kidney and the excretion DHT was paradoxically lower following its renal artery administration than following its peripheral injection. We interpret the latter to indicate that some kidney cells may contain receptors with very high affinity for DHT, thus leading to the lower excretion observed. The administration of androstenediol (into the renal artery) and E3 (peripherally) indicated that the diol was not conjugated as readily as E3. The results point to the ability of the kidney to conjugate testosterone to some extent; however, in no case was it able to conjugate an androgen with the same facility as it does E3."}
{"id": "PMID:194912", "title": "Insulin receptors in patients with insulinomas: changes in receptor affinity and concentration.", "content": "We have measured the specific binding of 125I-insulin to insulin receptors on circulating monocytes from 5 patients with insulinomas. In all patients the concentration of insulin receptors was inversely related to the basal, circulating level of insulin (corrected for proinsulin content). In the four patients with chronically elevated concentrations of plasma insulin, receptor concentrations were decreased. In three of these patients there were also marked alterations in receptor affinity. With insulinomas, correlations with the clinical state appear to be clearer when receptor concentration and especially receptor affinity are considered in addition to circulating insulin and proinsulin levels.", "contents": "Insulin receptors in patients with insulinomas: changes in receptor affinity and concentration. We have measured the specific binding of 125I-insulin to insulin receptors on circulating monocytes from 5 patients with insulinomas. In all patients the concentration of insulin receptors was inversely related to the basal, circulating level of insulin (corrected for proinsulin content). In the four patients with chronically elevated concentrations of plasma insulin, receptor concentrations were decreased. In three of these patients there were also marked alterations in receptor affinity. With insulinomas, correlations with the clinical state appear to be clearer when receptor concentration and especially receptor affinity are considered in addition to circulating insulin and proinsulin levels."}
{"id": "PMID:194914", "title": "Results of intermittent treatment of growth hormone deficiency with human grwoth hormone.", "content": "The growth in stature of two groups of growth hormone deficient children has been compared. The frist group received intermittent treatment with human Growth Hormone (hGH), 1 year on, 1 year off, subsequent years on; the second group received continous treatment. This latter group had a significantly better mean growth response. The reduction in treatment velocity in years subsequent to the first was not prevented by the year off treatment, the mean velocity of the intermittent group in their 3rd year being the same as that of the continous group in their second. We conclude that intermittent hGH therapy is of less values than continous treatment and should be avoided, at least pending further evidence.", "contents": "Results of intermittent treatment of growth hormone deficiency with human grwoth hormone. The growth in stature of two groups of growth hormone deficient children has been compared. The frist group received intermittent treatment with human Growth Hormone (hGH), 1 year on, 1 year off, subsequent years on; the second group received continous treatment. This latter group had a significantly better mean growth response. The reduction in treatment velocity in years subsequent to the first was not prevented by the year off treatment, the mean velocity of the intermittent group in their 3rd year being the same as that of the continous group in their second. We conclude that intermittent hGH therapy is of less values than continous treatment and should be avoided, at least pending further evidence."}
{"id": "PMID:194916", "title": "Serodiagnosis of viral hepatitis A: detection of acute-phase immunoglobulin M anti-hepatitis A virus by radioimmunoassay.", "content": "A modified micro solid-phase radioimmunoassay (RIA) for antibody to hepatitis A virus (anti-HAV) was developed. This double antibody procedure was performed by coating the surface of a polyvinyl microtiter plate \"well\" with 200 microliter of a 1:1,000 dilution of a patient's test serum. Purified HAV and 125I-labeled immunoglobulin G (IgG) anti-HAV were then sequentially added to form an antibody sandwich. The specificity and sensitivity of the RIA procedure for anti-HAV were verified by examination of coded human and chimpanzee serum specimens. Radioimmunoassay of early-acute-phase serum specimens from human cases of hepatitis A revealed the presence of anti-HAV activity. Differential examination by RIA of IgG and IgM fractions of acute-phase sera from experimentally infected chimpanzees demonstrated that IgM contained the bulk of the anti-HAV activity. A modification of the RIA procedure for anti-HAV (RIA-IgM blocking), incorporating an incubation step with anti-IgM (Mu chain specific), was further shown to differentiate acute- from convalescent-phase hepatitis A sera. This adapted RIA-IgM blocking procedure required less than 1 microliter of a single acute-phase serum specimen for the diagnosis of viral hepatitis A.", "contents": "Serodiagnosis of viral hepatitis A: detection of acute-phase immunoglobulin M anti-hepatitis A virus by radioimmunoassay. A modified micro solid-phase radioimmunoassay (RIA) for antibody to hepatitis A virus (anti-HAV) was developed. This double antibody procedure was performed by coating the surface of a polyvinyl microtiter plate \"well\" with 200 microliter of a 1:1,000 dilution of a patient's test serum. Purified HAV and 125I-labeled immunoglobulin G (IgG) anti-HAV were then sequentially added to form an antibody sandwich. The specificity and sensitivity of the RIA procedure for anti-HAV were verified by examination of coded human and chimpanzee serum specimens. Radioimmunoassay of early-acute-phase serum specimens from human cases of hepatitis A revealed the presence of anti-HAV activity. Differential examination by RIA of IgG and IgM fractions of acute-phase sera from experimentally infected chimpanzees demonstrated that IgM contained the bulk of the anti-HAV activity. A modification of the RIA procedure for anti-HAV (RIA-IgM blocking), incorporating an incubation step with anti-IgM (Mu chain specific), was further shown to differentiate acute- from convalescent-phase hepatitis A sera. This adapted RIA-IgM blocking procedure required less than 1 microliter of a single acute-phase serum specimen for the diagnosis of viral hepatitis A."}
{"id": "PMID:194917", "title": "Rapid biochemical tests for characterization of the Mycoplasmatales.", "content": "Methods are described for the rapid detection of beta-D-glucosidase and phosphatase in mycoplasma cultures using fluorogenic 4-methylumbelliferone substrates. These methods were applied to a selection of mycoplasma cultures and were compared with the conventionally used tests for these enzymes. Results were similar by both methods, but the fluorogenic tests could be read after 1 h, whereas the conventional tests took several days.", "contents": "Rapid biochemical tests for characterization of the Mycoplasmatales. Methods are described for the rapid detection of beta-D-glucosidase and phosphatase in mycoplasma cultures using fluorogenic 4-methylumbelliferone substrates. These methods were applied to a selection of mycoplasma cultures and were compared with the conventionally used tests for these enzymes. Results were similar by both methods, but the fluorogenic tests could be read after 1 h, whereas the conventional tests took several days."}
{"id": "PMID:194918", "title": "Variables affecting viral plaque formation in microculture plaque assays using homologous antibody in a liquid overlay.", "content": "A liquid antibody microculture plaque assay and the variables that govern its effectiveness are described. The assay is based on the principle that low concentrations of homologous antibody can inhibit secondary plaque formation without inhibiting formation of primary plaques. Thus, clear plaques that followed a linear dose response were produced. The assay was found to be more rapid, less cumbersome, and less expensive than assays using agar overlays and larger tissue culture plates. It was reproducible, quantitative, and had about the same sensitivity as the agar overlay technique in measuring infectious coxsackievirus type B-3. It was more sensitive in assaying adenovirus type 3 and Western equine encephalomyelitis, vesicular stomatitis, Semliki forest, Sendai, Sindbis, and Newcastle disease viruses than were liquid, carboxymethylcellulose, and methylcellulose microculture plaque assays. The variables influencing sensitivity and accuracy, as determined by using coxsackievirus type B-3, were: (i) the inoculum volume of virus; (ii) the incubation period of virus; and (iii) the incubation temperature.", "contents": "Variables affecting viral plaque formation in microculture plaque assays using homologous antibody in a liquid overlay. A liquid antibody microculture plaque assay and the variables that govern its effectiveness are described. The assay is based on the principle that low concentrations of homologous antibody can inhibit secondary plaque formation without inhibiting formation of primary plaques. Thus, clear plaques that followed a linear dose response were produced. The assay was found to be more rapid, less cumbersome, and less expensive than assays using agar overlays and larger tissue culture plates. It was reproducible, quantitative, and had about the same sensitivity as the agar overlay technique in measuring infectious coxsackievirus type B-3. It was more sensitive in assaying adenovirus type 3 and Western equine encephalomyelitis, vesicular stomatitis, Semliki forest, Sendai, Sindbis, and Newcastle disease viruses than were liquid, carboxymethylcellulose, and methylcellulose microculture plaque assays. The variables influencing sensitivity and accuracy, as determined by using coxsackievirus type B-3, were: (i) the inoculum volume of virus; (ii) the incubation period of virus; and (iii) the incubation temperature."}
{"id": "PMID:194919", "title": "Radioimmunoassay of human apolipoprotein CII. A study in normal and hypertriglyceridemic subjects.", "content": "A specific, precise, and sensitive double-antibody radioimmunoassay for the measurement of human apolipoprotein CII (apoCII) was developed. ApoCII was labeled with (125)I (chloramine-T) and monospecific antibody was raised in rabbits. No appreciable cross-reactivity with apolipoproteins CI, CIII, AI, AII, low density lipoproteins, and lipoprotein-free plasma was observed. Lipoproteins containing apoCII displaced the standard curve in parallel. ApoCII measurement was not affected by pretreatment of plasma with tetramethylurea, ethanol-diethyl ether, or heating. Mean (+/-SE) plasma-immunoreactive apoCII in 47 normotriglyceridemic subjects was 51.8+/-3.2 mug/ml, generally comparable with previous estimates of its concentration by other methods. ApoCII levels in 9 subjects with type IIB lipoprotein pattern, 14 with the type IV lipoprotein pattern, and 5 with type V lipoprotein pattern were respectively, 89.9+/-4.6, 85.4+/-6.9, 132.8+/-21.0 mug/ml, all higher than normals (P < 0.001). Plasma apoCII and triglyceride concentrations correlated in normo- and hypertriglyceridemics (r = 0.36 and 0.58, P < 0.05). Plasma triglycerides correlated inversely with the fraction of total apoCII in very low density lipoprotein (VLDL)-free plasma (r = -0.75, P < 0.01). There was no correlation between plasma apoCII and high density lipoprotein cholesterol. In normotriglyceridemics, VLDL apoCII levels correlated with in vitro lipoprotein lipase (LPL) activator activities (r = 0.89, P < 0.01). In hypertriglyceridemic subjects the mean concentrations of apoCII per milligrams VLDL protein, LPL activator activity per milligrams VLDL protein, and LPL activator activity per micrograms VLDL apoCII were all lower than in normotriglyceridemics, P < 0.05. As plasma triglycerides and apoCII increase, apoCII is redistributed from high density lipoprotein to VLDL. However, the amount of apoCII per milligram VLDL protein and its LPL activator potency per milligram VLDL protein are reduced. These factors may contribute to impaired VLDL catabolism.", "contents": "Radioimmunoassay of human apolipoprotein CII. A study in normal and hypertriglyceridemic subjects. A specific, precise, and sensitive double-antibody radioimmunoassay for the measurement of human apolipoprotein CII (apoCII) was developed. ApoCII was labeled with (125)I (chloramine-T) and monospecific antibody was raised in rabbits. No appreciable cross-reactivity with apolipoproteins CI, CIII, AI, AII, low density lipoproteins, and lipoprotein-free plasma was observed. Lipoproteins containing apoCII displaced the standard curve in parallel. ApoCII measurement was not affected by pretreatment of plasma with tetramethylurea, ethanol-diethyl ether, or heating. Mean (+/-SE) plasma-immunoreactive apoCII in 47 normotriglyceridemic subjects was 51.8+/-3.2 mug/ml, generally comparable with previous estimates of its concentration by other methods. ApoCII levels in 9 subjects with type IIB lipoprotein pattern, 14 with the type IV lipoprotein pattern, and 5 with type V lipoprotein pattern were respectively, 89.9+/-4.6, 85.4+/-6.9, 132.8+/-21.0 mug/ml, all higher than normals (P < 0.001). Plasma apoCII and triglyceride concentrations correlated in normo- and hypertriglyceridemics (r = 0.36 and 0.58, P < 0.05). Plasma triglycerides correlated inversely with the fraction of total apoCII in very low density lipoprotein (VLDL)-free plasma (r = -0.75, P < 0.01). There was no correlation between plasma apoCII and high density lipoprotein cholesterol. In normotriglyceridemics, VLDL apoCII levels correlated with in vitro lipoprotein lipase (LPL) activator activities (r = 0.89, P < 0.01). In hypertriglyceridemic subjects the mean concentrations of apoCII per milligrams VLDL protein, LPL activator activity per milligrams VLDL protein, and LPL activator activity per micrograms VLDL apoCII were all lower than in normotriglyceridemics, P < 0.05. As plasma triglycerides and apoCII increase, apoCII is redistributed from high density lipoprotein to VLDL. However, the amount of apoCII per milligram VLDL protein and its LPL activator potency per milligram VLDL protein are reduced. These factors may contribute to impaired VLDL catabolism."}
{"id": "PMID:194920", "title": "Isolation and characterization of an abnormal high density lipoprotein in Tangier Diesase.", "content": "The nature of the high density lipoproteins has been investigated in five patients homozygous for Tangier disease (familial high density lipoprotein deficiency). It has been established that Tangier high density lipoproteins, as isolated by ultracentrifugation, are morphologically heterogenous and contain several proteins (Apo B, albumin, and Apo A-II). An abnormal lipoprotein has been isolated from the d = 1.063-1.21 g/ml ultracentrifugal fraction by agarose-column chromatography which contains apoprotein A-II as the sole protein constituent. In negative-stain electron microscopy, these lipoproteins appeared as spherical particles 55-75 A in diameter. By a variety of criteria (immunochemical, polyacrylamide electrophoresis, amino acid composition, and fluorescence measurements), apoprotein A-I the major apoprotein of normal high density lipoproteins and the C apoproteins were absent from this lipoprotein. As demonstrated by (125)I very low density lipoprotein incubation experiments with Tangier plasma, C apoproteins did not associate with lipoproteins of d = 1.063-1.21 g/ml. Tangier apoprotein A-II, isolated to homogeneity by delipidation of the apoprotein A-II-containing lipoprotein or Sephadex G-200 guanidine-HCl chromatography of the d = 1.063-1.21 g/ml fraction, was indistinguishable from control apoprotein A-II with respect to amino acid composition and migration of tryptic peptides in urea-polyacrylamide electrophoresis. The ability of Tangier apoprotein A-II to bind phospholipid was demonstrated by in vitro reconstitution experiments and morphological and chemical analysis of lipid-protein complexes. It is concluded that normal high density lipoproteins, as defined by polypeptide composition and morphological appearance, are absent from Tangier plasma and that as a consequence, the impairment of C apoprotein metabolism contributes to the hypertriglyceridemia and fasting chylomicronemia observed in these patients.", "contents": "Isolation and characterization of an abnormal high density lipoprotein in Tangier Diesase. The nature of the high density lipoproteins has been investigated in five patients homozygous for Tangier disease (familial high density lipoprotein deficiency). It has been established that Tangier high density lipoproteins, as isolated by ultracentrifugation, are morphologically heterogenous and contain several proteins (Apo B, albumin, and Apo A-II). An abnormal lipoprotein has been isolated from the d = 1.063-1.21 g/ml ultracentrifugal fraction by agarose-column chromatography which contains apoprotein A-II as the sole protein constituent. In negative-stain electron microscopy, these lipoproteins appeared as spherical particles 55-75 A in diameter. By a variety of criteria (immunochemical, polyacrylamide electrophoresis, amino acid composition, and fluorescence measurements), apoprotein A-I the major apoprotein of normal high density lipoproteins and the C apoproteins were absent from this lipoprotein. As demonstrated by (125)I very low density lipoprotein incubation experiments with Tangier plasma, C apoproteins did not associate with lipoproteins of d = 1.063-1.21 g/ml. Tangier apoprotein A-II, isolated to homogeneity by delipidation of the apoprotein A-II-containing lipoprotein or Sephadex G-200 guanidine-HCl chromatography of the d = 1.063-1.21 g/ml fraction, was indistinguishable from control apoprotein A-II with respect to amino acid composition and migration of tryptic peptides in urea-polyacrylamide electrophoresis. The ability of Tangier apoprotein A-II to bind phospholipid was demonstrated by in vitro reconstitution experiments and morphological and chemical analysis of lipid-protein complexes. It is concluded that normal high density lipoproteins, as defined by polypeptide composition and morphological appearance, are absent from Tangier plasma and that as a consequence, the impairment of C apoprotein metabolism contributes to the hypertriglyceridemia and fasting chylomicronemia observed in these patients."}
{"id": "PMID:194921", "title": "The measurement of apolipoprotein A-I and A-II levels in men and women by immunoassay.", "content": "To study apolipoprotein A-II, a simple, precise, and accurate immunodiffusion assay was developed and applied in a population sample of industrial employees. Apolipoprotein A-II (A-II) did not increase with age in men (r = -0.20, n = 172), but showed a slight increase with age in women (0.1 mg/dl per yr, r = 0.20, n = 188). A-II correlated significantly with apolipoprotein A-I (A-I) (r = 0.71) and high density lipoprotein (HDL) cholesterol (men, r = 0.64; women, r = 0.49). The A-I/A-II ratio was significantly related to HDL cholesterol (men, r = 0.29; women, r = 0.44). Women on no medication (n = 92) had A-II levels similar to men (34+/-5 and 33+/-5 mg/dl, mean+/-SD, respectively), whereas women on oral contraceptives or estrogens had significantly higher levels (39+/-6 mg/dl, n = 75, P < 0.01). The plasma A-I/A-II weight ratio was 3.6+/-0.4 for men and 3.8+/-0.5 for women. In the d = 1.10-1.21 subfraction, both males and females had similar A-I, A-II, and HDL cholesterol levels (men: mean, 97, 27, and 32 mg/dl, respectively; women: mean, 104, 28, and 36 mg/dl, respectively). Women had approximately twice the amount of A-I, A-II, and HDL cholesterol than men in the d = 1.063-1.10 fraction (men: mean, 10, 2, and 10 mg/dl, respectively; women: mean, 24, 4, and 19 mg/dl, respectively). The A-I/A-II weight ratio in the d = 1.063-1.10 fraction (men, 5.1+/-0.7; women, 6.1+/-1.3) was significantly greater (P < 0.01) than that in the d = 1.10-1.21 fraction (men, 3.7+/-0.2; women, 3.8+/-0.2). Furthermore, the weight ratio of cholesterol to total apoprotein A in the d = 1.063-1.10 fraction (men, 0.75+/-0.09; women, 0.67+/-0.05) was significantly higher (P < 0.01) than that found in the d = 1.10-1.21 fraction (men, 0.26+/-0.04, women, 0.28+/-0.05). Thus, the compositions of HDL hydrated density subclasses are significantly different from each other. These results suggest that the differences in HDL between men and women are due primarily to differences in the relative proportions of HDL subclasses rather than to the intrinsic differences in HDL structure.", "contents": "The measurement of apolipoprotein A-I and A-II levels in men and women by immunoassay. To study apolipoprotein A-II, a simple, precise, and accurate immunodiffusion assay was developed and applied in a population sample of industrial employees. Apolipoprotein A-II (A-II) did not increase with age in men (r = -0.20, n = 172), but showed a slight increase with age in women (0.1 mg/dl per yr, r = 0.20, n = 188). A-II correlated significantly with apolipoprotein A-I (A-I) (r = 0.71) and high density lipoprotein (HDL) cholesterol (men, r = 0.64; women, r = 0.49). The A-I/A-II ratio was significantly related to HDL cholesterol (men, r = 0.29; women, r = 0.44). Women on no medication (n = 92) had A-II levels similar to men (34+/-5 and 33+/-5 mg/dl, mean+/-SD, respectively), whereas women on oral contraceptives or estrogens had significantly higher levels (39+/-6 mg/dl, n = 75, P < 0.01). The plasma A-I/A-II weight ratio was 3.6+/-0.4 for men and 3.8+/-0.5 for women. In the d = 1.10-1.21 subfraction, both males and females had similar A-I, A-II, and HDL cholesterol levels (men: mean, 97, 27, and 32 mg/dl, respectively; women: mean, 104, 28, and 36 mg/dl, respectively). Women had approximately twice the amount of A-I, A-II, and HDL cholesterol than men in the d = 1.063-1.10 fraction (men: mean, 10, 2, and 10 mg/dl, respectively; women: mean, 24, 4, and 19 mg/dl, respectively). The A-I/A-II weight ratio in the d = 1.063-1.10 fraction (men, 5.1+/-0.7; women, 6.1+/-1.3) was significantly greater (P < 0.01) than that in the d = 1.10-1.21 fraction (men, 3.7+/-0.2; women, 3.8+/-0.2). Furthermore, the weight ratio of cholesterol to total apoprotein A in the d = 1.063-1.10 fraction (men, 0.75+/-0.09; women, 0.67+/-0.05) was significantly higher (P < 0.01) than that found in the d = 1.10-1.21 fraction (men, 0.26+/-0.04, women, 0.28+/-0.05). Thus, the compositions of HDL hydrated density subclasses are significantly different from each other. These results suggest that the differences in HDL between men and women are due primarily to differences in the relative proportions of HDL subclasses rather than to the intrinsic differences in HDL structure."}
{"id": "PMID:194922", "title": "Stimulation of gastrin secretion and synthesis in antral organ culture.", "content": "The purpose of the present study was to examine stimulation of gastrin release and the synthesis of gastrin directly by measurement of incorporation of [(3)H]tryptophan into gastrin in rat antral mucosal explants maintained in organ culture. Gastrin synthesis and secretion were assessed simultaneously at intervals over the 24-h duration of explant culture. Antral mucosal explants from fed female Wistar rats (4-5 wk, 100-150 g) were cultured at 37 degrees C (95% O(2)/5% CO(2)) in medium containing 70% Trowell-T8 and 10% NCTC-135 without unlabeled tryptophan, 10% dialyzed fetal calf serum and [(3)H]tryptophan (100 muCi/ml). Antral tissue was harvested at regular intervals during 24-h culture periods. Incorporation of [(3)H]tryptophan into immunoreactive gastrin was determined by techniques utilizing double-antibody immunoprecipitation. Antral tissue protein synthesis was assessed by measurements of incorporation of [(3)H]tryptophan into tissue protein of cultured antral explants. In paired experiments, gastrin synthesis and secretion in the presence of dibutyryl cAMP (DBCAMP) were compared to those observed under control conditions. Gastrin and protein specific activity progressively increased with time. Gastrin specific activity at 30 min increased from 3.3+/-0.5 (SEM) to 55.2+/-10.6 fmol [(3)H]tryptophan/pmol gastrin (or from 1.57+/-0.48 to 26.28+/-5.05 pmol [(3)H]tryptophan/mug gastrin) at 24 h: specific activity of antral tissue protein at 30 min increased from 33.6+/-8.4 to 1,660+/-236 fmol [(3)H]tryptophan/mug protein at 16 h. Culturing of explants for 4 h in the presence of cycloheximide (100 mug/ml) inhibited both gastrin synthesis and protein synthesis by greater than 90 and 95%, respectively. DBCAMP (10 mM) significantly increased both the synthesis and secretion of antral gastrin when compared with control cultured explants. Results of these experiments provide direct demonstration of gastrin synthesis by rat antral mucosal explants in organ culture, indicate that both gastrin and total antral protein synthesis are inhibited by cycloheximide, and demonstrate DBCAMP-induced stimulation of both gastrin synthesis and secretion, suggesting the potentially important role of cyclic AMP in gastrin cell function.", "contents": "Stimulation of gastrin secretion and synthesis in antral organ culture. The purpose of the present study was to examine stimulation of gastrin release and the synthesis of gastrin directly by measurement of incorporation of [(3)H]tryptophan into gastrin in rat antral mucosal explants maintained in organ culture. Gastrin synthesis and secretion were assessed simultaneously at intervals over the 24-h duration of explant culture. Antral mucosal explants from fed female Wistar rats (4-5 wk, 100-150 g) were cultured at 37 degrees C (95% O(2)/5% CO(2)) in medium containing 70% Trowell-T8 and 10% NCTC-135 without unlabeled tryptophan, 10% dialyzed fetal calf serum and [(3)H]tryptophan (100 muCi/ml). Antral tissue was harvested at regular intervals during 24-h culture periods. Incorporation of [(3)H]tryptophan into immunoreactive gastrin was determined by techniques utilizing double-antibody immunoprecipitation. Antral tissue protein synthesis was assessed by measurements of incorporation of [(3)H]tryptophan into tissue protein of cultured antral explants. In paired experiments, gastrin synthesis and secretion in the presence of dibutyryl cAMP (DBCAMP) were compared to those observed under control conditions. Gastrin and protein specific activity progressively increased with time. Gastrin specific activity at 30 min increased from 3.3+/-0.5 (SEM) to 55.2+/-10.6 fmol [(3)H]tryptophan/pmol gastrin (or from 1.57+/-0.48 to 26.28+/-5.05 pmol [(3)H]tryptophan/mug gastrin) at 24 h: specific activity of antral tissue protein at 30 min increased from 33.6+/-8.4 to 1,660+/-236 fmol [(3)H]tryptophan/mug protein at 16 h. Culturing of explants for 4 h in the presence of cycloheximide (100 mug/ml) inhibited both gastrin synthesis and protein synthesis by greater than 90 and 95%, respectively. DBCAMP (10 mM) significantly increased both the synthesis and secretion of antral gastrin when compared with control cultured explants. Results of these experiments provide direct demonstration of gastrin synthesis by rat antral mucosal explants in organ culture, indicate that both gastrin and total antral protein synthesis are inhibited by cycloheximide, and demonstrate DBCAMP-induced stimulation of both gastrin synthesis and secretion, suggesting the potentially important role of cyclic AMP in gastrin cell function."}
{"id": "PMID:194923", "title": "Interaction between high density and low density lipoproteins uptake and degradation by cultured human fibroblasts.", "content": "High density lipoprotein (HDL) inhibited the binding (trypsin-releasable radioactivity), internalization (cell-associated radioactivity after trypsinization), and degradation (TCA-soluble non-iodide radioactivity) of (125)I-low density lipoprotein ((125)I-LDL) by cultured normal human fibroblasts. At HDL:LDL molar ratios of 25:1 (protein ratios about 5:1), these parameters were reduced by about 25%. Unlabeled LDL was about 25 times more effective in reducing (125)I-LDL binding, implying that if HDL and LDL bind at common sites the affinity of HDL for these sites is very low or that the interaction is on some other basis. The fractional reduction in (125)I-LDL binding at a given HDL: (125)I-LDL ratio was independent of (125)I-LDL concentration and occurred equally with fibroblasts from a subject with homozygous familial hypercholesterolemia. Reciprocally, the binding, internalization, and degradation of (125)I-HDL were reduced by LDL. Preincubation of fibroblasts with HDL (or LDL) reduced the subsequent binding of (125)I-LDL (or (125)I-HDL) during a second incubation. In other studies HDL reduced the net increase in cell cholesterol content induced by incubation with LDL. HDL alone had no net effect on cell cholesterol content. These findings suggest that HDL reduces both the high affinity and the low affinity binding of LDL to human fibroblasts and that this in turn reduces the internalization and degradation of LDL. The effect of HDL on the LDL-induced changes in cell cholesterol content could be in part on this basis and in part on the basis of an HDL-stimulated release of cholesterol from the cells. These effects of HDL in vitro may be relevant to the negative correlations reported from in vivo studies between plasma HDL concentration and both body cholesterol pool size and the prevalence of clinically manifest atherosclerosis but further studies will be needed to establish this.", "contents": "Interaction between high density and low density lipoproteins uptake and degradation by cultured human fibroblasts. High density lipoprotein (HDL) inhibited the binding (trypsin-releasable radioactivity), internalization (cell-associated radioactivity after trypsinization), and degradation (TCA-soluble non-iodide radioactivity) of (125)I-low density lipoprotein ((125)I-LDL) by cultured normal human fibroblasts. At HDL:LDL molar ratios of 25:1 (protein ratios about 5:1), these parameters were reduced by about 25%. Unlabeled LDL was about 25 times more effective in reducing (125)I-LDL binding, implying that if HDL and LDL bind at common sites the affinity of HDL for these sites is very low or that the interaction is on some other basis. The fractional reduction in (125)I-LDL binding at a given HDL: (125)I-LDL ratio was independent of (125)I-LDL concentration and occurred equally with fibroblasts from a subject with homozygous familial hypercholesterolemia. Reciprocally, the binding, internalization, and degradation of (125)I-HDL were reduced by LDL. Preincubation of fibroblasts with HDL (or LDL) reduced the subsequent binding of (125)I-LDL (or (125)I-HDL) during a second incubation. In other studies HDL reduced the net increase in cell cholesterol content induced by incubation with LDL. HDL alone had no net effect on cell cholesterol content. These findings suggest that HDL reduces both the high affinity and the low affinity binding of LDL to human fibroblasts and that this in turn reduces the internalization and degradation of LDL. The effect of HDL on the LDL-induced changes in cell cholesterol content could be in part on this basis and in part on the basis of an HDL-stimulated release of cholesterol from the cells. These effects of HDL in vitro may be relevant to the negative correlations reported from in vivo studies between plasma HDL concentration and both body cholesterol pool size and the prevalence of clinically manifest atherosclerosis but further studies will be needed to establish this."}
{"id": "PMID:194924", "title": "Stimulation by alcohols of cyclic AMP metabolism in human leukocytes. Possible role of cyclic AMP in the anti-inflammatory effects of ethanol.", "content": "In this study ethanol and certain other short-chain aryl (benzyl and phenethyl) and aliphatic (methyl, propyl, butyl, and amyl) alcohols produced up to 10-fold increases in cyclic AMP (cAMP) concentrations in purified human peripheral blood lymphocytes. Ethanol concentrations as low as 80 mg/dl produced significant elevations in lymphocyte cAMP. Significant but less marked augmentation of cAMP in response to alcohols was observed in human platelets, human granulocytes, and rabbit alveolar macrophages. The mechanism of the alcohol-induced cAMP accumulation is probably secondary to membrane perturbation and consequent activation of adenylate cyclase, because ethanol directly stimulated this enzyme in lymphocyte membrane preparations but had no effect on lymphocyte phosphodiesterase activity. Lysosomal enzyme release, by phagocytosing human leukocytes, and aminoisobutyric acid transport in mitogen-stimulated human lymphocytes were shown to be inhibited by ethanol and other alcohols at concentrations which also elevate cAMP. In general, the magnitude of the inhibition of these inflammatory processes correlated with the ability of the alcohol to elevate cAMP concentrations. Lectin-and anti-thymocyte globulin-induced lymphocyte mitogenesis was inhibited or unaffected depending upon both the concentration and type of mitogenic stimulus and the concentration and type of alcohol utilized. Inflammatory mediator release from rat mast cells also was inhibited by ethanol and certain other alcohols, but whole cell cAMP was not increased. Ethanol may alter these inflammatory responses and other biologic processes at least in part by modulating cellular levels of cAMP.", "contents": "Stimulation by alcohols of cyclic AMP metabolism in human leukocytes. Possible role of cyclic AMP in the anti-inflammatory effects of ethanol. In this study ethanol and certain other short-chain aryl (benzyl and phenethyl) and aliphatic (methyl, propyl, butyl, and amyl) alcohols produced up to 10-fold increases in cyclic AMP (cAMP) concentrations in purified human peripheral blood lymphocytes. Ethanol concentrations as low as 80 mg/dl produced significant elevations in lymphocyte cAMP. Significant but less marked augmentation of cAMP in response to alcohols was observed in human platelets, human granulocytes, and rabbit alveolar macrophages. The mechanism of the alcohol-induced cAMP accumulation is probably secondary to membrane perturbation and consequent activation of adenylate cyclase, because ethanol directly stimulated this enzyme in lymphocyte membrane preparations but had no effect on lymphocyte phosphodiesterase activity. Lysosomal enzyme release, by phagocytosing human leukocytes, and aminoisobutyric acid transport in mitogen-stimulated human lymphocytes were shown to be inhibited by ethanol and other alcohols at concentrations which also elevate cAMP. In general, the magnitude of the inhibition of these inflammatory processes correlated with the ability of the alcohol to elevate cAMP concentrations. Lectin-and anti-thymocyte globulin-induced lymphocyte mitogenesis was inhibited or unaffected depending upon both the concentration and type of mitogenic stimulus and the concentration and type of alcohol utilized. Inflammatory mediator release from rat mast cells also was inhibited by ethanol and certain other alcohols, but whole cell cAMP was not increased. Ethanol may alter these inflammatory responses and other biologic processes at least in part by modulating cellular levels of cAMP."}
{"id": "PMID:194925", "title": "Hormonal control of adrenocortical cell proliferation. Desensitization to ACTH and interaction between ACTH and fibroblast growth factor in bovine adrenocortical cell cultures.", "content": "A primary bovine adrenocortical cell culture system responsive to physiological concentrations of ACTH has been established. When added to cultures, ACTH inhibited DNA synthesis and cell division over the same concentration range required for stimulation of fluorogenic steroid production (0.01-10 nM). With chronic exposure to ACTH, cells became desensitized to the growth inhibitory effects of ACTH. Though cell growth was initially completely inhibited by ACTH, cells ultimately began to grow in its continued presence. The lag time to initiation of cell growth, the rate of growth, and the final density achieved depended on the ACTH concentration. Desensitization to ACTH(1-39) was not induced by monobutyryl cyclic AMP nor by ACTH(11-24). Specificity of desensitization was apparent because cells which had become desensitized to ACTH(1-39) remained fully responsive to monobutyryl cyclic AMP, prostaglandin E(1), and cholera toxin. Though the effects of ACTH on cell growth were readily reversible upon hormone removal, the desensitized response to readdition of ACTH persisted for at least 8 h. Fibroblast growth factor (FGF) stimulated both the growth rate and saturation density achieved. FGF did not alter the growth inhibitory effects of ACTH nor the reduced growth rate observed in desensitized cells maintained in ACTH. However, FGF greatly increased the saturation density achieved by cultures maintained with ACTH. Through the process of desensitization, adrenocortical cells are able to grow in the presence of high concentrations of ACTH and to respond to the effects of a growth factor by increasing the cell density achieved. This pattern of response may be a general one for growth control under the combined effects of antimitotic and mitotic factors.", "contents": "Hormonal control of adrenocortical cell proliferation. Desensitization to ACTH and interaction between ACTH and fibroblast growth factor in bovine adrenocortical cell cultures. A primary bovine adrenocortical cell culture system responsive to physiological concentrations of ACTH has been established. When added to cultures, ACTH inhibited DNA synthesis and cell division over the same concentration range required for stimulation of fluorogenic steroid production (0.01-10 nM). With chronic exposure to ACTH, cells became desensitized to the growth inhibitory effects of ACTH. Though cell growth was initially completely inhibited by ACTH, cells ultimately began to grow in its continued presence. The lag time to initiation of cell growth, the rate of growth, and the final density achieved depended on the ACTH concentration. Desensitization to ACTH(1-39) was not induced by monobutyryl cyclic AMP nor by ACTH(11-24). Specificity of desensitization was apparent because cells which had become desensitized to ACTH(1-39) remained fully responsive to monobutyryl cyclic AMP, prostaglandin E(1), and cholera toxin. Though the effects of ACTH on cell growth were readily reversible upon hormone removal, the desensitized response to readdition of ACTH persisted for at least 8 h. Fibroblast growth factor (FGF) stimulated both the growth rate and saturation density achieved. FGF did not alter the growth inhibitory effects of ACTH nor the reduced growth rate observed in desensitized cells maintained in ACTH. However, FGF greatly increased the saturation density achieved by cultures maintained with ACTH. Through the process of desensitization, adrenocortical cells are able to grow in the presence of high concentrations of ACTH and to respond to the effects of a growth factor by increasing the cell density achieved. This pattern of response may be a general one for growth control under the combined effects of antimitotic and mitotic factors."}
{"id": "PMID:194926", "title": "Evidence for hydroxyl radical generation by human Monocytes.", "content": "A number of highly reactive oxygen species have been implicated in the oxygen-dependent mechanisms involved in bactericidal activity of phagocytic leukocytes. Hydrogen peroxide and superoxide, two agents known to occur during phagocytosis, are thought to interact to generate hydroxyl radical, singlet oxygen, and other potentially reactive molecules. Using an assay system of ethylene generation from methional, cell preparations of human monocytes were demonstrated to generate hydroxyl radical or a similar agent during phagocytosis of zymosan particles. The generation of ethylene was impaired by agents which reduce superoxide or hydrogen peroxide concentrations as well as by agents reported to be hydroxyl radical scavengers. The ethylene generation did not appear to be dependent on myeloperoxidase in that azide enhanced ethylene generation. Monocytes from a patient with chronic granulomatous disease failed to generate ethylene during phagocytosis. This assay technique may be useful in exploring the metabolic events integral to the bactericidal and inflammatory activity of phagocytic leukocytes.", "contents": "Evidence for hydroxyl radical generation by human Monocytes. A number of highly reactive oxygen species have been implicated in the oxygen-dependent mechanisms involved in bactericidal activity of phagocytic leukocytes. Hydrogen peroxide and superoxide, two agents known to occur during phagocytosis, are thought to interact to generate hydroxyl radical, singlet oxygen, and other potentially reactive molecules. Using an assay system of ethylene generation from methional, cell preparations of human monocytes were demonstrated to generate hydroxyl radical or a similar agent during phagocytosis of zymosan particles. The generation of ethylene was impaired by agents which reduce superoxide or hydrogen peroxide concentrations as well as by agents reported to be hydroxyl radical scavengers. The ethylene generation did not appear to be dependent on myeloperoxidase in that azide enhanced ethylene generation. Monocytes from a patient with chronic granulomatous disease failed to generate ethylene during phagocytosis. This assay technique may be useful in exploring the metabolic events integral to the bactericidal and inflammatory activity of phagocytic leukocytes."}
{"id": "PMID:194927", "title": "Aetiology of cirrhosis, hepatic fibrosis, and hepatocellular carcinoma.", "content": "Histological study of 69 cases of cirrhosis, 9 of severe generalised hepatic fibrosis, and 19 of hepatocellular carcinoma showed an association with alcohol, hepatitis B surface antigen (HBsAg) or a1-antitrypsin bodies in, respectively, 41 (cirrhosis), 5 (fibrosis), and 9 (carcinoma). Eight of the cirrhotic cases and two of the carcinoma cases had double associations, HBsAg being present in all. Torcein and aldehyde fuchsin staining gave both false positive and false negative results when compared with immunofluorescence and immunoperoxidase methods for HBsAg. Large amounts of copper were found in four cirrhotic livers, and moderate amounts in 13: the diagnostic value of copper staining is questioned.", "contents": "Aetiology of cirrhosis, hepatic fibrosis, and hepatocellular carcinoma. Histological study of 69 cases of cirrhosis, 9 of severe generalised hepatic fibrosis, and 19 of hepatocellular carcinoma showed an association with alcohol, hepatitis B surface antigen (HBsAg) or a1-antitrypsin bodies in, respectively, 41 (cirrhosis), 5 (fibrosis), and 9 (carcinoma). Eight of the cirrhotic cases and two of the carcinoma cases had double associations, HBsAg being present in all. Torcein and aldehyde fuchsin staining gave both false positive and false negative results when compared with immunofluorescence and immunoperoxidase methods for HBsAg. Large amounts of copper were found in four cirrhotic livers, and moderate amounts in 13: the diagnostic value of copper staining is questioned."}
{"id": "PMID:194930", "title": "Pancreatic scanning using retrograde injection of technetium-99m-labeled compounds.", "content": "With increased clinical availability of endoscopic retrograde pancreatography, a method for retrograde injection of radionuclides into the pancreas became available. A dog model was developed to evaluate resolution and toxicity of retrograde imaging prior to human use. Two groups of technetium-99m-labeled compounds were used. The first included ionic carriers--pertechnetate and pyrophosphate--and the second included particulate carriers--sulfur colloid and albumin microspheres. Parenchymal visualization, absorption patterns, and toxicity in dogs were studied. The results suggest that pyrophosphate, sulfur colloid, and albumin microspheres would all be feasible technetium carriers for use in humans.", "contents": "Pancreatic scanning using retrograde injection of technetium-99m-labeled compounds. With increased clinical availability of endoscopic retrograde pancreatography, a method for retrograde injection of radionuclides into the pancreas became available. A dog model was developed to evaluate resolution and toxicity of retrograde imaging prior to human use. Two groups of technetium-99m-labeled compounds were used. The first included ionic carriers--pertechnetate and pyrophosphate--and the second included particulate carriers--sulfur colloid and albumin microspheres. Parenchymal visualization, absorption patterns, and toxicity in dogs were studied. The results suggest that pyrophosphate, sulfur colloid, and albumin microspheres would all be feasible technetium carriers for use in humans."}
{"id": "PMID:194931", "title": "Myocardial imaging with Cc-99m pyrophosphate in patients on adriamycin treatment for neoplasia.", "content": "Technetium-99m pyrophosphate was utilized for myocardial imaging in 15 patients on adriamycin treatment for neoplasia. We have noted abnormal accumulation of the pyrophosphate in several patients, particularly in those in whom the so-called poor-risk factors were operative, namely prior radiation, cyclophosphamide therapy, and ischemic heart disease.", "contents": "Myocardial imaging with Cc-99m pyrophosphate in patients on adriamycin treatment for neoplasia. Technetium-99m pyrophosphate was utilized for myocardial imaging in 15 patients on adriamycin treatment for neoplasia. We have noted abnormal accumulation of the pyrophosphate in several patients, particularly in those in whom the so-called poor-risk factors were operative, namely prior radiation, cyclophosphamide therapy, and ischemic heart disease."}
{"id": "PMID:194932", "title": "Diagnosis of acute myocardial infarction in patients undergoing open heart surgery: a comparison of serial myocardial imaging with cardiac enzymes, electrocardiography, and vectorcardiography.", "content": "In 44 consecutive patients undergoing elective open heart surgery (OHS), serial electrocardiograms (ECG), vectorcardiograms (VCG), serum CPK, cardiac isoenzymes (CPKMB), and myocardial images using Tc-99m pyrophosphate were obtained, before and after the operation, for the detection of acute myocardial infarction (AMI). Twenty-nine patients developed one or more positive tests postoperatively. Two patients had positive myocardial scintiscans; both had other evidence of infarction. Conversely, the appearance of CPKMB, or new ECG and VCG changes, occurred frequently without evidence of infarction, and were not associated with the development of a positive scintiscan. The results show that false-negative results are infrequent in patients imaged early after OHS, and that cardiac surgical procedures do not cause a high incidence of false-positive scintigrams. Consequently, radionuclide imaging for AMI offers an important adjunct for excluding acute infarction following open heart surgery.", "contents": "Diagnosis of acute myocardial infarction in patients undergoing open heart surgery: a comparison of serial myocardial imaging with cardiac enzymes, electrocardiography, and vectorcardiography. In 44 consecutive patients undergoing elective open heart surgery (OHS), serial electrocardiograms (ECG), vectorcardiograms (VCG), serum CPK, cardiac isoenzymes (CPKMB), and myocardial images using Tc-99m pyrophosphate were obtained, before and after the operation, for the detection of acute myocardial infarction (AMI). Twenty-nine patients developed one or more positive tests postoperatively. Two patients had positive myocardial scintiscans; both had other evidence of infarction. Conversely, the appearance of CPKMB, or new ECG and VCG changes, occurred frequently without evidence of infarction, and were not associated with the development of a positive scintiscan. The results show that false-negative results are infrequent in patients imaged early after OHS, and that cardiac surgical procedures do not cause a high incidence of false-positive scintigrams. Consequently, radionuclide imaging for AMI offers an important adjunct for excluding acute infarction following open heart surgery."}
{"id": "PMID:194933", "title": "The significance of calcific valvular heart disease in Tc-99m pyrophosphate myocardial infarction scanning: radiographic, scintigraphic, and pathological correlation.", "content": "Technetium-99m pyrophosphate (PPi) is currently considered the best scanning agent for the diagnosis of acute myocardial infarction. False-positive scans have been reported in association with unstable angina, alcoholic cardiomyopathy, and ventricular aneurysms. In this study, 86% of patients (12/14) with either calcific aortic or mitral valvular heart disease had positive PPi cardiac scintiscans and the location of the PPi uptake was limited to the calcific valve in all (9/9) of the patients who underwent valve replacement surgery. Six patients with valvular disease without radiologic evidence of calcium had negative PPi heart images. Three of these patients had surgical valve replacement, and in none was there increased uptake in the resected valve. Seventy-five percent of the patients with calcified aortic valves had localization of the PPi activity to the area of the aortic valve, whereas 50% of the patients with calcified mitral valves showed a diffuse pattern of uptake on the cardiac image. In vitro demonstration of increased radioactivity in surgically removed cardiac valves warrants the conclusion that Tc-99m PPi is taken up by calcified heart valves. We conclude that while PPi heart scanning is a sensitive indicator of acute myocardial infarction, false-positive scans can occur in the presence of calcific valvular disease, due to localization of PPi in the calcified portion of the valve.", "contents": "The significance of calcific valvular heart disease in Tc-99m pyrophosphate myocardial infarction scanning: radiographic, scintigraphic, and pathological correlation. Technetium-99m pyrophosphate (PPi) is currently considered the best scanning agent for the diagnosis of acute myocardial infarction. False-positive scans have been reported in association with unstable angina, alcoholic cardiomyopathy, and ventricular aneurysms. In this study, 86% of patients (12/14) with either calcific aortic or mitral valvular heart disease had positive PPi cardiac scintiscans and the location of the PPi uptake was limited to the calcific valve in all (9/9) of the patients who underwent valve replacement surgery. Six patients with valvular disease without radiologic evidence of calcium had negative PPi heart images. Three of these patients had surgical valve replacement, and in none was there increased uptake in the resected valve. Seventy-five percent of the patients with calcified aortic valves had localization of the PPi activity to the area of the aortic valve, whereas 50% of the patients with calcified mitral valves showed a diffuse pattern of uptake on the cardiac image. In vitro demonstration of increased radioactivity in surgically removed cardiac valves warrants the conclusion that Tc-99m PPi is taken up by calcified heart valves. We conclude that while PPi heart scanning is a sensitive indicator of acute myocardial infarction, false-positive scans can occur in the presence of calcific valvular disease, due to localization of PPi in the calcified portion of the valve."}
{"id": "PMID:194929", "title": "Hemostasis by premedication with estrogen in hair-transplant surgery.", "content": "Premedication with water-soluble conjugated estrogens administered the previous day and a half-hour before operation diminished bleeding and allows for a drier field, better vision and quicker work. Post-operative bleeding is negligible. Their short-term use has not led to feminization nor presented cardiovascular problems.", "contents": "Hemostasis by premedication with estrogen in hair-transplant surgery. Premedication with water-soluble conjugated estrogens administered the previous day and a half-hour before operation diminished bleeding and allows for a drier field, better vision and quicker work. Post-operative bleeding is negligible. Their short-term use has not led to feminization nor presented cardiovascular problems."}
{"id": "PMID:194934", "title": "Comparison of Tc-99m methylene diphosphonate with Tc-99m pyrophosphate in the detection of acute myocardial infarction: concise communication.", "content": "Myocardial scans were obtained in ten patients with proven myocardial infarction. Scintigraphy on consecutive days was performed with technetium-99m methylene diphosphonate and technetium-99m pyrophosphate. Images obtained with the two tracers were generally equal in quality. Those with PPi exhibited denser uptake, while background activity was lower with MDP.", "contents": "Comparison of Tc-99m methylene diphosphonate with Tc-99m pyrophosphate in the detection of acute myocardial infarction: concise communication. Myocardial scans were obtained in ten patients with proven myocardial infarction. Scintigraphy on consecutive days was performed with technetium-99m methylene diphosphonate and technetium-99m pyrophosphate. Images obtained with the two tracers were generally equal in quality. Those with PPi exhibited denser uptake, while background activity was lower with MDP."}
{"id": "PMID:194935", "title": "A comparative study on lysosomal accumulation of gallium-67 and indium-111 in Morris hepatoma 7316A.", "content": "Intracellular localization of Ga-67 and In-111 was investigated in Morris hepatoma 7316A and in normal Buffalo rat liver cells by a cell fractionation method at 48 hr after an intraperitoneal injection of the nuclides. Lysosomal fractions of the tumor and normal liver cells had the highest relative specific radioactivities of the nuclides (p less than 0.001). In a gradual solubilization experiment, the release of the nuclides at the same time as the acid phosphatase from the lysosomal fractions (p less than 0.001) was thought to indicate that lysosomes are the site of accumulation for both nuclides whether in tumor or normal liver cells. Fragility of the tumor lysosomes might be inferred from the significantly greater regression coefficient in relation to the lysosomal fraction of tumor cells than that of normal liver cells when labeled with Ga-67 (p less than 0.001). The poorer confidence limit for the regression coefficient in relation to the lysosomal fraction of tumor cells labeled with Ga-67 seemed to indicate that Ga-67 determines lysosomal functions of tumor cells more precisely than In-111.", "contents": "A comparative study on lysosomal accumulation of gallium-67 and indium-111 in Morris hepatoma 7316A. Intracellular localization of Ga-67 and In-111 was investigated in Morris hepatoma 7316A and in normal Buffalo rat liver cells by a cell fractionation method at 48 hr after an intraperitoneal injection of the nuclides. Lysosomal fractions of the tumor and normal liver cells had the highest relative specific radioactivities of the nuclides (p less than 0.001). In a gradual solubilization experiment, the release of the nuclides at the same time as the acid phosphatase from the lysosomal fractions (p less than 0.001) was thought to indicate that lysosomes are the site of accumulation for both nuclides whether in tumor or normal liver cells. Fragility of the tumor lysosomes might be inferred from the significantly greater regression coefficient in relation to the lysosomal fraction of tumor cells than that of normal liver cells when labeled with Ga-67 (p less than 0.001). The poorer confidence limit for the regression coefficient in relation to the lysosomal fraction of tumor cells labeled with Ga-67 seemed to indicate that Ga-67 determines lysosomal functions of tumor cells more precisely than In-111."}
{"id": "PMID:194936", "title": "Absence of the effect of ephedrine on levels of cyclic adenosine monophosphate in human lymphocytes.", "content": "Concentrations of 10(-6) to 10(-3) M ephedrine did not increase cyclic adenosine monophosphate (cAMP) levels of normal human lymphocytes even in the presence of theophylline or cortisol, which enhance the response to isoproterenol or prostaglandin E1. Preincubation for 2 hr with ephedrine did not reduce the subsequent effect of isoproterenol, although preincubation with isoproterenol itself did. Therefore, ephedrine is not a direct beta-adrenergic agonist on human peripheral blood lymphocytes.", "contents": "Absence of the effect of ephedrine on levels of cyclic adenosine monophosphate in human lymphocytes. Concentrations of 10(-6) to 10(-3) M ephedrine did not increase cyclic adenosine monophosphate (cAMP) levels of normal human lymphocytes even in the presence of theophylline or cortisol, which enhance the response to isoproterenol or prostaglandin E1. Preincubation for 2 hr with ephedrine did not reduce the subsequent effect of isoproterenol, although preincubation with isoproterenol itself did. Therefore, ephedrine is not a direct beta-adrenergic agonist on human peripheral blood lymphocytes."}
{"id": "PMID:194950", "title": "The ocular manifestations of congenital infections produced by toxoplasma and cytomegalovirus.", "content": "Chorioretinitis is the most common ocular manifestation of congenital toxoplasmosis occurring in both symptomatic and the more freqeunt subclinical form of the disease. Chorioretinitis also occurs in symptomatic congenital cytomegalovirus (CMV) but not in the subclinical form of this congenital congenital infection. Diagnosis cannot be made from ocular signs alone. Knowledge of the epidemiology of both congenital infections along with information about the postnatal history will assist in the differentiation.", "contents": "The ocular manifestations of congenital infections produced by toxoplasma and cytomegalovirus. Chorioretinitis is the most common ocular manifestation of congenital toxoplasmosis occurring in both symptomatic and the more freqeunt subclinical form of the disease. Chorioretinitis also occurs in symptomatic congenital cytomegalovirus (CMV) but not in the subclinical form of this congenital congenital infection. Diagnosis cannot be made from ocular signs alone. Knowledge of the epidemiology of both congenital infections along with information about the postnatal history will assist in the differentiation."}
{"id": "PMID:194979", "title": "Dietary control of hyperlipidaemia. Dietitians in the EEC: 2. Republic of Ireland.", "content": "One hundred and ten adult out-patients entered a prospective study of the effect of dietary control of hyperlipidaemia. Seventy-nine were male and 31 female. Eighty-four patients had primary type II and 26 had primary type IV hyperlipidaemia. Cases of secondary hyperlipidaemia were excluded. Patients with type II hyperlipidaemia were treated with a diet low in saturated fat and cholesterol, with substitution of polyunsaturated fats. Additional carbohydrate and alcohol restriction was applied to patients with type IV hyperlipidaemia. Calorie restriction was prescribed for overweight patients. In type II patients, mean serum cholesterol fell from 322 to 286 mg per 100 ml, and weight from 159 to 152 lb over the first six months of treatment. In type IV patients cholesterol fell from 328 to 281 mg per 100 ml, triglycerides from 389 to 241 mg per 100 ml and weight from 166 to 156 lb over the same period. All reductions were statistically significant at the 1 per cent level. No statistical correlation was observed between reduction of weight and reduction in lipid levels. Over a three-year follow-up period no tendancy for lipid levels or weight to 'rebound' was noted. It is concluded that diet can produce a significant reduction in plasma lipid levels over six months in some hyperlipidaemic patients. Further follow-up is continuing to determine whether this effect can be maintained over the longterm.", "contents": "Dietary control of hyperlipidaemia. Dietitians in the EEC: 2. Republic of Ireland. One hundred and ten adult out-patients entered a prospective study of the effect of dietary control of hyperlipidaemia. Seventy-nine were male and 31 female. Eighty-four patients had primary type II and 26 had primary type IV hyperlipidaemia. Cases of secondary hyperlipidaemia were excluded. Patients with type II hyperlipidaemia were treated with a diet low in saturated fat and cholesterol, with substitution of polyunsaturated fats. Additional carbohydrate and alcohol restriction was applied to patients with type IV hyperlipidaemia. Calorie restriction was prescribed for overweight patients. In type II patients, mean serum cholesterol fell from 322 to 286 mg per 100 ml, and weight from 159 to 152 lb over the first six months of treatment. In type IV patients cholesterol fell from 328 to 281 mg per 100 ml, triglycerides from 389 to 241 mg per 100 ml and weight from 166 to 156 lb over the same period. All reductions were statistically significant at the 1 per cent level. No statistical correlation was observed between reduction of weight and reduction in lipid levels. Over a three-year follow-up period no tendancy for lipid levels or weight to 'rebound' was noted. It is concluded that diet can produce a significant reduction in plasma lipid levels over six months in some hyperlipidaemic patients. Further follow-up is continuing to determine whether this effect can be maintained over the longterm."}
{"id": "PMID:194981", "title": "Increased binding and killing of neuraminidase-galactose oxidase-treated tumor cells by normal macrophages.", "content": "The binding of Line 10 hepatoma cells to normal syngeneic guinea pig macrophages is increased when the tumor cells are treated with neuraminidase and galactose oxidase (NAGO) before they are added to the macrophage monolayers. The effect is abolished by exposure of the NAGO-treated tumor cells to sodium borohydride. Line 1 hepatoma cells treated with NAGO or with sodium periodate are killed to a greater extent than untreated tumor cells. This effect can also be reversed by sodium borohydride. Further, periodate-treated macrophages become cytotoxic for unmodified tumor cells. These results demonstrate that increased tumor cell killing occurs when artificial contacts (presumably via Schiff bases) are established between normal macrophages and tumor cells. They are consistent with the hypothesis that close cell to cell contact is necessary for macrophage-mediated cytotoxicity.", "contents": "Increased binding and killing of neuraminidase-galactose oxidase-treated tumor cells by normal macrophages. The binding of Line 10 hepatoma cells to normal syngeneic guinea pig macrophages is increased when the tumor cells are treated with neuraminidase and galactose oxidase (NAGO) before they are added to the macrophage monolayers. The effect is abolished by exposure of the NAGO-treated tumor cells to sodium borohydride. Line 1 hepatoma cells treated with NAGO or with sodium periodate are killed to a greater extent than untreated tumor cells. This effect can also be reversed by sodium borohydride. Further, periodate-treated macrophages become cytotoxic for unmodified tumor cells. These results demonstrate that increased tumor cell killing occurs when artificial contacts (presumably via Schiff bases) are established between normal macrophages and tumor cells. They are consistent with the hypothesis that close cell to cell contact is necessary for macrophage-mediated cytotoxicity."}
{"id": "PMID:194982", "title": "Migration inhibition by an agarose microdroplet assay: monitoring of tumor-associated antigens on a simian virus 40-induced sarcoma.", "content": "Macrophage migration inhibition assays, with a direct agarose microdroplet method, were used to monitor TAA activity of preparations of SV-40-induced mKSA cells. These preparations included cell-free crude membranes, papain-solubilized and NP40 detergent-solubilized membrane extracts from mKSA tumor cells. The assay was extremely sensitive and could detect migration inhibition reactivity with all three types of antigenic preparations with concentrations as low at 250 ng protein/ml. The reactivities were quite reproducible from experiment to experiment using the same or different lots of these antigen preparations, and the reactivities were specific in that peritoneal exudate cells from BALB/c mice, immunized with antigenically unrelated but syngeneic plasmacytomas, were not inhibited by these antigens. The results demonstrated the usefulness of this assay in rapidly detecting small concentrations of partially purified TAA preparations by using small number of immune cells.", "contents": "Migration inhibition by an agarose microdroplet assay: monitoring of tumor-associated antigens on a simian virus 40-induced sarcoma. Macrophage migration inhibition assays, with a direct agarose microdroplet method, were used to monitor TAA activity of preparations of SV-40-induced mKSA cells. These preparations included cell-free crude membranes, papain-solubilized and NP40 detergent-solubilized membrane extracts from mKSA tumor cells. The assay was extremely sensitive and could detect migration inhibition reactivity with all three types of antigenic preparations with concentrations as low at 250 ng protein/ml. The reactivities were quite reproducible from experiment to experiment using the same or different lots of these antigen preparations, and the reactivities were specific in that peritoneal exudate cells from BALB/c mice, immunized with antigenically unrelated but syngeneic plasmacytomas, were not inhibited by these antigens. The results demonstrated the usefulness of this assay in rapidly detecting small concentrations of partially purified TAA preparations by using small number of immune cells."}
{"id": "PMID:194983", "title": "Reactivity to SV40 T antigen in athymic (nude), anti-thymocyte serum-treated, and normal mice.", "content": "Antisera prepared in syngeneic mice by hyperimmunization with intact SV40-transformed mouse cells or with somatic cell hybrids between SV40-transformed human and normal mouse cells exhibit anti-SV40 tumor (T) antigen reactivity. Athymic mice bearing tumors formed by SV40-transformed mouse, human or mouse-human hybrids were not reactive with SV40 T antigen. Anti-thymocyte serum (ATS)-treated mice also lacked T antigen reactivity during suppressive treatment but developed antibody to T antigen after discontinuing ATS treatment and tumor regression. We conclude that that presence of growing tumors in the mouse is not necessary for the production of anti-SV40 T antigen antibodies but that helper thymus-derived cells are essential for the humoral response.", "contents": "Reactivity to SV40 T antigen in athymic (nude), anti-thymocyte serum-treated, and normal mice. Antisera prepared in syngeneic mice by hyperimmunization with intact SV40-transformed mouse cells or with somatic cell hybrids between SV40-transformed human and normal mouse cells exhibit anti-SV40 tumor (T) antigen reactivity. Athymic mice bearing tumors formed by SV40-transformed mouse, human or mouse-human hybrids were not reactive with SV40 T antigen. Anti-thymocyte serum (ATS)-treated mice also lacked T antigen reactivity during suppressive treatment but developed antibody to T antigen after discontinuing ATS treatment and tumor regression. We conclude that that presence of growing tumors in the mouse is not necessary for the production of anti-SV40 T antigen antibodies but that helper thymus-derived cells are essential for the humoral response."}
{"id": "PMID:194984", "title": "Cytotoxic interactions of virus specific effector cells with virus infected targets of different cell type.", "content": "The action of Sendai virus specific cytolytic T lumphocytes (CTL) against Sendai virus infected macrophages was found to be H-2 restricted while Sendai virus infected cell lines, including fibroblasts and tumour cells, were lysed across the H-2 barrier to some extent. The properties of the Meth-A tumour cell, which was resistant to lysis by allogenic killer cells was investigated. Sendai virus specific CTL failed to kill Sendai virus infected Meth-A cells but after vaccinia virus infection these target cells were susceptible to lysis by vaccinia virus specific CTL.", "contents": "Cytotoxic interactions of virus specific effector cells with virus infected targets of different cell type. The action of Sendai virus specific cytolytic T lumphocytes (CTL) against Sendai virus infected macrophages was found to be H-2 restricted while Sendai virus infected cell lines, including fibroblasts and tumour cells, were lysed across the H-2 barrier to some extent. The properties of the Meth-A tumour cell, which was resistant to lysis by allogenic killer cells was investigated. Sendai virus specific CTL failed to kill Sendai virus infected Meth-A cells but after vaccinia virus infection these target cells were susceptible to lysis by vaccinia virus specific CTL."}
{"id": "PMID:194985", "title": "A linkage study of rabbit serum high density lipoprotein (HDL) allotypes.", "content": "Close linkage between the two allotypic systems of rabbit serum high density lipoprotein (HDL), Hl 1 and R 67, has been confidently excluded, the recombination fraction being at least 0-20. No suggestion of linkage between either HDL allotype and the immunoglobulin allotypes a1a2a3/b4b9, or the red blood cell system (RBC) ADF was obtained. Close linkage was confidently excluded for the Hl 1-ADF, Hl 1-a1a2a3, R 67-ADF, R 67-a1a2a3, R 67-b4b9, a1a2a3-b4b9, and b4b9-ADF relationships.", "contents": "A linkage study of rabbit serum high density lipoprotein (HDL) allotypes. Close linkage between the two allotypic systems of rabbit serum high density lipoprotein (HDL), Hl 1 and R 67, has been confidently excluded, the recombination fraction being at least 0-20. No suggestion of linkage between either HDL allotype and the immunoglobulin allotypes a1a2a3/b4b9, or the red blood cell system (RBC) ADF was obtained. Close linkage was confidently excluded for the Hl 1-ADF, Hl 1-a1a2a3, R 67-ADF, R 67-a1a2a3, R 67-b4b9, a1a2a3-b4b9, and b4b9-ADF relationships."}
{"id": "PMID:194986", "title": "Controlling influences of the autonomic nervous system.", "content": "Recent information about the localization of sympathetic nerves and catecholamine-containing cells suggests sites of action not usually described in the neuroscience textbooks. In this study, we focused on the autonomic controls that affect ganglia, heart, gut, and chemoreceptors. As a result of some speculation derived mainly from histochemical observations and partially from physiologic data, we concluded that at the organ level the interplay between a nerve terminal-receptor serves as a local control. Additional controls may function at the ganglion level where catecholamine-containing chromaffin cells may serve as interneurons. We suggest that all peripheral catecholamine-containing elements which function in a modulatory role are not vital to the survival of the individual but rather serve as \"fine tune\" adjustment that do not involve the central nervous system.", "contents": "Controlling influences of the autonomic nervous system. Recent information about the localization of sympathetic nerves and catecholamine-containing cells suggests sites of action not usually described in the neuroscience textbooks. In this study, we focused on the autonomic controls that affect ganglia, heart, gut, and chemoreceptors. As a result of some speculation derived mainly from histochemical observations and partially from physiologic data, we concluded that at the organ level the interplay between a nerve terminal-receptor serves as a local control. Additional controls may function at the ganglion level where catecholamine-containing chromaffin cells may serve as interneurons. We suggest that all peripheral catecholamine-containing elements which function in a modulatory role are not vital to the survival of the individual but rather serve as \"fine tune\" adjustment that do not involve the central nervous system."}
{"id": "PMID:194987", "title": "Disorders of peripheral cutaneous nerves.", "content": "The histopathology of leprosy is described with particular reference to its effects on peripheral cutaneous nerves. Mycobacterium leprae invade the Schwann and perineurial cells of peripheral cutaneous nerves preferentially. The organisms are eventually destroyed with their host cells by a cell-mediated immune response. The effect is a dying-back phenomenon without the formation of neuromata. The sensory effects are gradually increasing anesthesia and localized nerve trunk pain but seldom any peripheral sensory reference or paresthesiae. Peripheral nerves are shown to be zones where there is some degree of immunologic privilege for Myco. leprae.", "contents": "Disorders of peripheral cutaneous nerves. The histopathology of leprosy is described with particular reference to its effects on peripheral cutaneous nerves. Mycobacterium leprae invade the Schwann and perineurial cells of peripheral cutaneous nerves preferentially. The organisms are eventually destroyed with their host cells by a cell-mediated immune response. The effect is a dying-back phenomenon without the formation of neuromata. The sensory effects are gradually increasing anesthesia and localized nerve trunk pain but seldom any peripheral sensory reference or paresthesiae. Peripheral nerves are shown to be zones where there is some degree of immunologic privilege for Myco. leprae."}
{"id": "PMID:194989", "title": "C-peptide suppression test for insulinoma.", "content": "During hypoglycemia induced by an infusion of porcine insulin, impaired suppression of endogenous insulin secretion as measured by C-peptide was demonstrated in 11 of 12 patients with insulinoma. During hypoglycemia (plasma glucose less than or equal to 40 mg/dl) the mean C-peptide immunoreactivity (CPR) of normal subjects was less than or equal to 1.2 ng/ml, whereas 11 of 12 insulinoma patients had a mean CPR of larger than or equal to 1.9 ng/ml. One patient showed normal CPR suppression by these criteria but may have shown impaired CPR suppression for glucose less than or equal to 30 mg/dl. Impaired CPR suppression during insulin-induced hypoglycemia may prove to be a useful test for insulinoma.", "contents": "C-peptide suppression test for insulinoma. During hypoglycemia induced by an infusion of porcine insulin, impaired suppression of endogenous insulin secretion as measured by C-peptide was demonstrated in 11 of 12 patients with insulinoma. During hypoglycemia (plasma glucose less than or equal to 40 mg/dl) the mean C-peptide immunoreactivity (CPR) of normal subjects was less than or equal to 1.2 ng/ml, whereas 11 of 12 insulinoma patients had a mean CPR of larger than or equal to 1.9 ng/ml. One patient showed normal CPR suppression by these criteria but may have shown impaired CPR suppression for glucose less than or equal to 30 mg/dl. Impaired CPR suppression during insulin-induced hypoglycemia may prove to be a useful test for insulinoma."}
{"id": "PMID:194991", "title": "99mTc-pyrophosphate bone scans in patients with metastatic carcinoid tumors.", "content": "Three patients with foregut (bronchial), hindgut (rectal) or (ovarian) carcinoid tumors had symptomatic bone metastasis with abnormal 99m Tc pyrophosphate bone scans and bone roentgenograms. Six patients with midgut (small intestine or caecal) carcinoid) carcinoid tumors who had no symptoms of bone metastasis had no evidence of bone metastasis on bone scan or bone roentgenographic examination. This study supports the clinical impression that patients with midget carcinoid tumors have a low incidence of bone metastasis.", "contents": "99mTc-pyrophosphate bone scans in patients with metastatic carcinoid tumors. Three patients with foregut (bronchial), hindgut (rectal) or (ovarian) carcinoid tumors had symptomatic bone metastasis with abnormal 99m Tc pyrophosphate bone scans and bone roentgenograms. Six patients with midgut (small intestine or caecal) carcinoid) carcinoid tumors who had no symptoms of bone metastasis had no evidence of bone metastasis on bone scan or bone roentgenographic examination. This study supports the clinical impression that patients with midget carcinoid tumors have a low incidence of bone metastasis."}
{"id": "PMID:194993", "title": "Dynamics and mechanics of corticosteroid feedback at the hypothalamus and anterior pituitary gland.", "content": "Corticosteroid feedback mechanisms were investigated at the hypothalamic level using the rat hypothalamus in vitro and the pituitary level using basal hypthalamic-lesioned rats. Both fast and delayed corticosteroid feedback effects were demonstrated at the level of the hypothalamus and pituitary gland with doses of corticosteroids within or near the physiological range. These two phases of feedback were separated temporally by a 'silent period' during which no feedback was apparent. Studies on the mechanism of action of corticosteroids at the hypothalamic level showed that the fast feedback mechanism acts by inhibition of release whilst the delayed feedback mechanism acts by inhibition of both synthesis and release. The fast feedback action of corticosterone does not appear to act by excitation of neuroinhibitory pathways since neither picrotoxin nor phentolamine prevented the feedback action of corticosteroids in vitro. Corticosterone inhibition of corticotrophin releasing factor release was overcome by depolarization of the membrane with K+ suggesting that the mechanism of action of the fast feedback of corticosteroids is by membrane stabilization.", "contents": "Dynamics and mechanics of corticosteroid feedback at the hypothalamus and anterior pituitary gland. Corticosteroid feedback mechanisms were investigated at the hypothalamic level using the rat hypothalamus in vitro and the pituitary level using basal hypthalamic-lesioned rats. Both fast and delayed corticosteroid feedback effects were demonstrated at the level of the hypothalamus and pituitary gland with doses of corticosteroids within or near the physiological range. These two phases of feedback were separated temporally by a 'silent period' during which no feedback was apparent. Studies on the mechanism of action of corticosteroids at the hypothalamic level showed that the fast feedback mechanism acts by inhibition of release whilst the delayed feedback mechanism acts by inhibition of both synthesis and release. The fast feedback action of corticosterone does not appear to act by excitation of neuroinhibitory pathways since neither picrotoxin nor phentolamine prevented the feedback action of corticosteroids in vitro. Corticosterone inhibition of corticotrophin releasing factor release was overcome by depolarization of the membrane with K+ suggesting that the mechanism of action of the fast feedback of corticosteroids is by membrane stabilization."}
{"id": "PMID:194994", "title": "Temporal changes in ovarian ornithine decarboxylase and cyclic AMP in immature rats stimulated by exogenous or endogenous gonadotrophins.", "content": "Pregnant mare serum gonadotrophin given intravenously to immature rats caused a maximal (x 70) increase in ornithine decarboxylase activity (ODC) at 3 h; enzyme activity declined to about ten times the control levels by 9 h and a second rise began after about 20 h. Anti-PMSG given 30 min after PMSG reduced the peak response by 70%. Actinomycin D, or cycloheximide, completely prevented an increase in ODC when given with PMSG, but only cycloheximide lowered the enzyme activity when given 18 h later. Ovine FSH plus LH also produced a peak in ODC at 3 h but the activity decreased quickly and by 9 h it was at the control level. Secretion of endogenous FSH and LH, induced by hourly injections of LH releasing hormone (LH-RH) increased ODC to the same extent as did the exogenous hormones; ODC was still higher than in the controls 4 h after the last dose of LH-RH. Increased endogenous levels of FSH and LH did not consistently raise ovarian cyclic AMP content and the increases found were much less than those obtained after injection of PMSG or FSH+LH. The results indicate that increased ODC is induced and maintained by the continual presence of gonadotrophin. The dependence of increased ODC upon increased cyclic AMP cannot be unequivocally determined because of important differences in the timing of the responses and the difficulty in determining biologically significant changes in cyclic AMP.", "contents": "Temporal changes in ovarian ornithine decarboxylase and cyclic AMP in immature rats stimulated by exogenous or endogenous gonadotrophins. Pregnant mare serum gonadotrophin given intravenously to immature rats caused a maximal (x 70) increase in ornithine decarboxylase activity (ODC) at 3 h; enzyme activity declined to about ten times the control levels by 9 h and a second rise began after about 20 h. Anti-PMSG given 30 min after PMSG reduced the peak response by 70%. Actinomycin D, or cycloheximide, completely prevented an increase in ODC when given with PMSG, but only cycloheximide lowered the enzyme activity when given 18 h later. Ovine FSH plus LH also produced a peak in ODC at 3 h but the activity decreased quickly and by 9 h it was at the control level. Secretion of endogenous FSH and LH, induced by hourly injections of LH releasing hormone (LH-RH) increased ODC to the same extent as did the exogenous hormones; ODC was still higher than in the controls 4 h after the last dose of LH-RH. Increased endogenous levels of FSH and LH did not consistently raise ovarian cyclic AMP content and the increases found were much less than those obtained after injection of PMSG or FSH+LH. The results indicate that increased ODC is induced and maintained by the continual presence of gonadotrophin. The dependence of increased ODC upon increased cyclic AMP cannot be unequivocally determined because of important differences in the timing of the responses and the difficulty in determining biologically significant changes in cyclic AMP."}
{"id": "PMID:194995", "title": "Binding of human chorionic gonadotrophin to rat ovary during development.", "content": "Ovarian tissue of prenatal, newborn, and 5-day-old rats does not specifically bind 125I-labelled HCG. Specific binding of HCG was first observed in ovaries of 10-day-old animals and binding increased with age. These results indicate that, contrary to rat testis, the HCG receptor in the rat ovary is not present during foetal and early postnatal development. Thus, the insensitivity of the ovary to endogenous and exogenous LH or HCG during this developmental period is due to the lack of specific receptors.", "contents": "Binding of human chorionic gonadotrophin to rat ovary during development. Ovarian tissue of prenatal, newborn, and 5-day-old rats does not specifically bind 125I-labelled HCG. Specific binding of HCG was first observed in ovaries of 10-day-old animals and binding increased with age. These results indicate that, contrary to rat testis, the HCG receptor in the rat ovary is not present during foetal and early postnatal development. Thus, the insensitivity of the ovary to endogenous and exogenous LH or HCG during this developmental period is due to the lack of specific receptors."}
{"id": "PMID:194997", "title": "Renal uptake and metabolism of adrenocorticotrophin analogues in the rat: an autoradiographic study.", "content": "Renal resorption of tritiated adrenocorticotrophin analogues was studied in the rat using light microscopic and quantitative electron microscopic autoradiography. The synthetic corticotrophins used were Synacthen (corticotrophin-(1-24)-tetracosapeptide) and C41795-Ba ([D-Ser1,Lys17,Lys18]-corticotrophin-(1-18)-octadecapeptide amide), the tetracosapeptide being tritiated in either the tyrosine residue of position 2 or 23 or the phenylalanine of position 7 and the octadecapeptide in the tyrosine of position 2. Inspection of autoradiographs showed that peptides injected intravenously were resorbed into proximal tubules by endocytosis to produce vesicles whose radiolabel later appeared in lysosomes, a route previously elucidated for other peptides and proteins. The use of two techniques for analysis of electron microscopic autoradiographs, however, suggested that apical tubules also acquire label and are in some way involved in the transfer of resorbed labelled material from endocytotic vesicles to lysosomes. In addition, the autoradiographic analyses revealed that the duration of lysosomal labelling depends upon the position of tritium in the chain. Thus, when the CO2H-terminus of Synacthen was labelled, silver grains were more transiently associated with lysosomes than was the case when the NH2-terminal or core regions were tritiated, indicating a greater resistance of these portions of the peptide to attack by intracellular peptidase. The label from the chemically protected C 41795-Ba was also less readily expelled from the lysosomes of the proximal tubules.", "contents": "Renal uptake and metabolism of adrenocorticotrophin analogues in the rat: an autoradiographic study. Renal resorption of tritiated adrenocorticotrophin analogues was studied in the rat using light microscopic and quantitative electron microscopic autoradiography. The synthetic corticotrophins used were Synacthen (corticotrophin-(1-24)-tetracosapeptide) and C41795-Ba ([D-Ser1,Lys17,Lys18]-corticotrophin-(1-18)-octadecapeptide amide), the tetracosapeptide being tritiated in either the tyrosine residue of position 2 or 23 or the phenylalanine of position 7 and the octadecapeptide in the tyrosine of position 2. Inspection of autoradiographs showed that peptides injected intravenously were resorbed into proximal tubules by endocytosis to produce vesicles whose radiolabel later appeared in lysosomes, a route previously elucidated for other peptides and proteins. The use of two techniques for analysis of electron microscopic autoradiographs, however, suggested that apical tubules also acquire label and are in some way involved in the transfer of resorbed labelled material from endocytotic vesicles to lysosomes. In addition, the autoradiographic analyses revealed that the duration of lysosomal labelling depends upon the position of tritium in the chain. Thus, when the CO2H-terminus of Synacthen was labelled, silver grains were more transiently associated with lysosomes than was the case when the NH2-terminal or core regions were tritiated, indicating a greater resistance of these portions of the peptide to attack by intracellular peptidase. The label from the chemically protected C 41795-Ba was also less readily expelled from the lysosomes of the proximal tubules."}
{"id": "PMID:194998", "title": "Pituitary regulation of Leydig cell function in the adult male rat.", "content": "The effects of hypophysectomy on serum testosterone, 125I-labelled hCG binding to testicular membranes and on testicular responsiveness were studied in adult rats. Serum testosterone decreased rapidly over the first 6 h after hypophysectomy. LH receptors were determined (pmol/testis) by measuring the specific binding of 125I-labelled hCG in membrane preparations of testes of rats hypophysectomized 1, 2, 3, 6, 9, or 15 days earlier. Hypophysectomy did not result in a decrease in 125I-labelled hCG binding on day 1 but this had decreased to 40% of that in intact controls by day 2. A gradual decline was found between days 2 and 6 at which time hCG binding had decreased to 15%. No further decrease occurred between days 6 and 15. Scatchard analysis indicated that the decline in hCG binding was due to a decreaffinity. FSH, testosterone, dihydrotestosterone, and oestradiol were unable to prevent the decline in hCG binding. Although serum testosterone, testicular testosterone content, and 125I-labelled hCG binding decreased rapidly after hypophysectomy, testicular responsiveness to LH was biphasic. The intraperitoneal administration of 25 microgram LH 2 h before decapitation increased testosterone in the circulation to a greater extent extent in animals hypophysectomized for 1 day than in intact controls while hCG binding affinities and capacities had not changed. Two or three days after hypophysectomy testicular responsiveness to LH was similar to that of intact controls even though hCG binding in hypophysectomized animals had decreased to 40 and 28% of intact controls respectively. It is concluded that (1) the testis is dependent on anterior pituitary hormones for maintenance of testicular LH receptors and testosterone secretion, (2) FSH, testosterone, dihydrotestosterone, or oestradiol cannot prevent the decline in testicular LH receptors resulting from hypophysectomy, and (3) steroidogenic capacity of the testis persists significantly longer than the hCG binding capacity of the testis.", "contents": "Pituitary regulation of Leydig cell function in the adult male rat. The effects of hypophysectomy on serum testosterone, 125I-labelled hCG binding to testicular membranes and on testicular responsiveness were studied in adult rats. Serum testosterone decreased rapidly over the first 6 h after hypophysectomy. LH receptors were determined (pmol/testis) by measuring the specific binding of 125I-labelled hCG in membrane preparations of testes of rats hypophysectomized 1, 2, 3, 6, 9, or 15 days earlier. Hypophysectomy did not result in a decrease in 125I-labelled hCG binding on day 1 but this had decreased to 40% of that in intact controls by day 2. A gradual decline was found between days 2 and 6 at which time hCG binding had decreased to 15%. No further decrease occurred between days 6 and 15. Scatchard analysis indicated that the decline in hCG binding was due to a decreaffinity. FSH, testosterone, dihydrotestosterone, and oestradiol were unable to prevent the decline in hCG binding. Although serum testosterone, testicular testosterone content, and 125I-labelled hCG binding decreased rapidly after hypophysectomy, testicular responsiveness to LH was biphasic. The intraperitoneal administration of 25 microgram LH 2 h before decapitation increased testosterone in the circulation to a greater extent extent in animals hypophysectomized for 1 day than in intact controls while hCG binding affinities and capacities had not changed. Two or three days after hypophysectomy testicular responsiveness to LH was similar to that of intact controls even though hCG binding in hypophysectomized animals had decreased to 40 and 28% of intact controls respectively. It is concluded that (1) the testis is dependent on anterior pituitary hormones for maintenance of testicular LH receptors and testosterone secretion, (2) FSH, testosterone, dihydrotestosterone, or oestradiol cannot prevent the decline in testicular LH receptors resulting from hypophysectomy, and (3) steroidogenic capacity of the testis persists significantly longer than the hCG binding capacity of the testis."}
{"id": "PMID:194999", "title": "Differentiation of memory T cells to virus plaque-forming cells and cytotoxic T lymphocytes.", "content": "The aims of this study were to define the T-cell subpopulation(s) detected by the virus plaque assay, and particularly to determine whether the virus plaque assay could be used to enumerate cytotoxic T lymphocytes. In addition, studies were undertaken to ascertain whether cell proliferation was required for development of cytotoxic effector function and virus plaque formation by these subpopulations. The results of experiments with a secondary mouse mixed lymphocyte culture (MLC) model indicated that 70 percent of virus plaque-forming cells bore the Ly 1 phenotype and 30 percent the Ly 2,3 phenotype. Three lines of evidence suggested that cytotoxic T lymphocytes (CTL) can be detected by this assay: the fact that some virus plaque-forming cells (V-PFC) bear the same Ly phenotype as CTL; the use of an inhibitor of DNA synthesis indicated that proliferating cells could be eliminated with no effect on V-PFC production and cytotoxic activity of the Ly 2,3 cell population; and that infection of primed lymphocyteswith vesicular stomatitis virus before (MLC) stimulation eliminated cytotoxic activity. In primary MLC, development of V-PFC and CTL was completely abolished by cytosine arabinoside. In contrast, in secondary MLC, some CTL and V- PFC were generated by antigenic stimulation in the absence of proliferation. However, the development of both functions became progressively more susceptible to cytosine arabinoside as the time between primary immunization and in vitro boosting is increased. It is suggested that there may be a considerable disparity between the number of existing effector cells at any given time and the cytotoxic potential, i.e. the number of cells capable of being generated by antigenic stimulation.", "contents": "Differentiation of memory T cells to virus plaque-forming cells and cytotoxic T lymphocytes. The aims of this study were to define the T-cell subpopulation(s) detected by the virus plaque assay, and particularly to determine whether the virus plaque assay could be used to enumerate cytotoxic T lymphocytes. In addition, studies were undertaken to ascertain whether cell proliferation was required for development of cytotoxic effector function and virus plaque formation by these subpopulations. The results of experiments with a secondary mouse mixed lymphocyte culture (MLC) model indicated that 70 percent of virus plaque-forming cells bore the Ly 1 phenotype and 30 percent the Ly 2,3 phenotype. Three lines of evidence suggested that cytotoxic T lymphocytes (CTL) can be detected by this assay: the fact that some virus plaque-forming cells (V-PFC) bear the same Ly phenotype as CTL; the use of an inhibitor of DNA synthesis indicated that proliferating cells could be eliminated with no effect on V-PFC production and cytotoxic activity of the Ly 2,3 cell population; and that infection of primed lymphocyteswith vesicular stomatitis virus before (MLC) stimulation eliminated cytotoxic activity. In primary MLC, development of V-PFC and CTL was completely abolished by cytosine arabinoside. In contrast, in secondary MLC, some CTL and V- PFC were generated by antigenic stimulation in the absence of proliferation. However, the development of both functions became progressively more susceptible to cytosine arabinoside as the time between primary immunization and in vitro boosting is increased. It is suggested that there may be a considerable disparity between the number of existing effector cells at any given time and the cytotoxic potential, i.e. the number of cells capable of being generated by antigenic stimulation."}
{"id": "PMID:195000", "title": "Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection.", "content": "Studies were made on the identity of human and monkey mononuclear leukocytes permissive to antibody-enhanced dengue 2 virus (D2V) infection. In cultures of peripheral blood leukocytes (PBL) inoculated immediately after separation, it was concluded that only mononuclear phagocytes support dengue infection. This is based upon observations that D2V-permissive cells were resistant to 1,200 rads, were both plastic adherent and nonadherent, were removed when passed through nylon wool columns in 10 percent fetal bovine serum or 100 percent autologous serum, and were destroyed by incubation with 100 mug/ml particulate silica. On direct immunofluorescence staining, perinuclear dengue antigen was visualized at 24 h, becoming maximal at 60 h. Antigen-containing cells had ample cytoplasm, ruffled cytoplasmic membrane, and 73 percent were actively phagocytic. As further evidence of the infection of mononuclear phagocytes, antibody-enhanced D2V replication was observed in bone marrow cultures from five of five rhesus monkeys, but not in cell cultures of spleen, thymus, or lymph nodes prepared from the same animals. It is hypothesized that dengue virus complexed with non-neutralizing antibody is internalized by immune phagocytosis in a mononuclear phagocyte with a defective virus-destroying mechanism. Dengue permissiveness may depend upon cellular immaturity since bone marrow leukocytes could be infected even when held for 4 days before infection while PBL held for this time decreased in permissiveness. In vitro antibody-dependent infection of mononuclear phagocytes should prove useful as a model for study of immunopathologic mechanisms in human dengue.", "contents": "Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection. Studies were made on the identity of human and monkey mononuclear leukocytes permissive to antibody-enhanced dengue 2 virus (D2V) infection. In cultures of peripheral blood leukocytes (PBL) inoculated immediately after separation, it was concluded that only mononuclear phagocytes support dengue infection. This is based upon observations that D2V-permissive cells were resistant to 1,200 rads, were both plastic adherent and nonadherent, were removed when passed through nylon wool columns in 10 percent fetal bovine serum or 100 percent autologous serum, and were destroyed by incubation with 100 mug/ml particulate silica. On direct immunofluorescence staining, perinuclear dengue antigen was visualized at 24 h, becoming maximal at 60 h. Antigen-containing cells had ample cytoplasm, ruffled cytoplasmic membrane, and 73 percent were actively phagocytic. As further evidence of the infection of mononuclear phagocytes, antibody-enhanced D2V replication was observed in bone marrow cultures from five of five rhesus monkeys, but not in cell cultures of spleen, thymus, or lymph nodes prepared from the same animals. It is hypothesized that dengue virus complexed with non-neutralizing antibody is internalized by immune phagocytosis in a mononuclear phagocyte with a defective virus-destroying mechanism. Dengue permissiveness may depend upon cellular immaturity since bone marrow leukocytes could be infected even when held for 4 days before infection while PBL held for this time decreased in permissiveness. In vitro antibody-dependent infection of mononuclear phagocytes should prove useful as a model for study of immunopathologic mechanisms in human dengue."}
{"id": "PMID:195001", "title": "Preleukemic expression of TL antigens in x-irradiated C57BL/6 mice.", "content": "Anomalous appearance of TL (thymus-leukemia) antigens is a characteristic feature of radiation-induced leukemias of C57bl/6 mice. We now report that thymocytes of irradiated C57BL/6 mice express TL antigens long before the development of overt leukemia. Thus, TL is a marker for preleukemic changes occurring during radiation leukemogenesis. Low levels of murine leukemia virus (MuLV)-related antigens are also detected on preleukemic thymocytes. Comparative tests on individual mice show no direct correlation between TL and MuLV antigen expression.", "contents": "Preleukemic expression of TL antigens in x-irradiated C57BL/6 mice. Anomalous appearance of TL (thymus-leukemia) antigens is a characteristic feature of radiation-induced leukemias of C57bl/6 mice. We now report that thymocytes of irradiated C57BL/6 mice express TL antigens long before the development of overt leukemia. Thus, TL is a marker for preleukemic changes occurring during radiation leukemogenesis. Low levels of murine leukemia virus (MuLV)-related antigens are also detected on preleukemic thymocytes. Comparative tests on individual mice show no direct correlation between TL and MuLV antigen expression."}
{"id": "PMID:195002", "title": "Expression of AKR murine leukemia virus gp71-like and BALB(X) gp-71-like antigens in normal mouse tissues in the absence of overt virus expression.", "content": "By competition radioimmune assays with antisera against AKR murine leukemia virus (MuLV) gp 71 or antisera against xenotropic virus, and iodinated AKR MuLV gp71 or BALB(X) gp71, antigens serologically indistinguishable from the viral antigens can be detected in tissues of normal mice in the absence of overt virus expression. An antigen serologically indistinguishable from AKR MuLV gp71 can be readily detected in normal bone marrow cells of the common strains of mice including NIH Swiss, 129/J, and SWR/J, as well as in Mus cervicolor and Mus musculus casteneus. In contrast, this antigen is not detected in normal spleen, thymus, lymph nodes, or serum. Similarly, an antigen serologically indistinguishable from BALB(X) gp71 was found in all normal mouse sera examined. This antigen was not present in fetal liver, perfused adult liver, thymus, spleen, lymph nodes, or bone marrow of the mice examined. An equivalent antigen was detected in sera from Mus musculus casteneus but not in sera from Mus cervicolor.", "contents": "Expression of AKR murine leukemia virus gp71-like and BALB(X) gp-71-like antigens in normal mouse tissues in the absence of overt virus expression. By competition radioimmune assays with antisera against AKR murine leukemia virus (MuLV) gp 71 or antisera against xenotropic virus, and iodinated AKR MuLV gp71 or BALB(X) gp71, antigens serologically indistinguishable from the viral antigens can be detected in tissues of normal mice in the absence of overt virus expression. An antigen serologically indistinguishable from AKR MuLV gp71 can be readily detected in normal bone marrow cells of the common strains of mice including NIH Swiss, 129/J, and SWR/J, as well as in Mus cervicolor and Mus musculus casteneus. In contrast, this antigen is not detected in normal spleen, thymus, lymph nodes, or serum. Similarly, an antigen serologically indistinguishable from BALB(X) gp71 was found in all normal mouse sera examined. This antigen was not present in fetal liver, perfused adult liver, thymus, spleen, lymph nodes, or bone marrow of the mice examined. An equivalent antigen was detected in sera from Mus musculus casteneus but not in sera from Mus cervicolor."}
{"id": "PMID:195003", "title": "Influence of local anesthetics upon human polymorphonuclear leukocyte function in vitro. Reduction of lysosomal enzyme release and superoxide anion production.", "content": "Cationic local anesthetics have been reported to influence cellular responses to surface stimuli by interfering with the function of microtubules and microfilaments. Since unimpaired microtubule and microfilament functions are required by human polymorphonuclear leukocytes in order to respond normally to surface stimulation, we have studied effects of the local anesthetic, tetracaine on the function and morphology of these cells in vitro. Tetracaine (0.25--1.0 mM) significantly reduced extracellular release of the lysosomal enzymes, beta-glucuronidase and lysozyme from polymorphonuclear leukocytes exposed to serum-treated zymosan (a particulate stimulus), zymosan-treated serum (a soluble stimulus), and to the surface-active lectin, concanavalin A. Tetracaine also significantly reduced superoixde anion production (superoxide dismutase-inhibitable cytochrome c reduction) by these cells. Tetrancaine was not cytotoxic and its effects could be reversed completely by washing cells once with buffer. Electron microscope examination of tetracaine-treated cells revealed marked alterations of surface membranes. Microtubules and microfilaments appeared normal in \"resting\" polymorphonuclear leukocytes, but the increase in microtubules normally observed in stimulated cells was not seen after tetracaine treatment. These results suggest that tetracaine interferes with those interactions between immune reactants and the polymorphonuclear leukocyte cell surface which provoke exocytosis and increased oxidative metabolism.", "contents": "Influence of local anesthetics upon human polymorphonuclear leukocyte function in vitro. Reduction of lysosomal enzyme release and superoxide anion production. Cationic local anesthetics have been reported to influence cellular responses to surface stimuli by interfering with the function of microtubules and microfilaments. Since unimpaired microtubule and microfilament functions are required by human polymorphonuclear leukocytes in order to respond normally to surface stimulation, we have studied effects of the local anesthetic, tetracaine on the function and morphology of these cells in vitro. Tetracaine (0.25--1.0 mM) significantly reduced extracellular release of the lysosomal enzymes, beta-glucuronidase and lysozyme from polymorphonuclear leukocytes exposed to serum-treated zymosan (a particulate stimulus), zymosan-treated serum (a soluble stimulus), and to the surface-active lectin, concanavalin A. Tetracaine also significantly reduced superoixde anion production (superoxide dismutase-inhibitable cytochrome c reduction) by these cells. Tetrancaine was not cytotoxic and its effects could be reversed completely by washing cells once with buffer. Electron microscope examination of tetracaine-treated cells revealed marked alterations of surface membranes. Microtubules and microfilaments appeared normal in \"resting\" polymorphonuclear leukocytes, but the increase in microtubules normally observed in stimulated cells was not seen after tetracaine treatment. These results suggest that tetracaine interferes with those interactions between immune reactants and the polymorphonuclear leukocyte cell surface which provoke exocytosis and increased oxidative metabolism."}
{"id": "PMID:195004", "title": "Suppression of in vitro Epstein-Barr virus infection. A new role for adult human T lymphocytes.", "content": "Studies have been performed on in vitro infection by Epstein-Barr virus (EBV) of subpopulations of human lymphocytes. B cells of adult peripheral or fetal cord blood transform with equal efficiency, whether assayed by DNA synthesis induction or by outgrowth of transformed lymphocytes. In contrast, unfractionated adult lymphocytes transform much less efficiently than those from fetal cord. Reconstitution experiments of different cell preparations indicated that this difference was due to a suppression of B-cell proliferation by adult Ig-negative lymphocytes which fetal Ig-negative lymphocytes were unable to perform. Separation of Ig-negative lymphocytes into various subpopulations revealed that the suppression was performed by T cells. Macrophages and null cells play little or no role in suppression. The relevance of this phenomenon to infection and recovery from EBV infection during and after infectious mononucleosis is discussed.", "contents": "Suppression of in vitro Epstein-Barr virus infection. A new role for adult human T lymphocytes. Studies have been performed on in vitro infection by Epstein-Barr virus (EBV) of subpopulations of human lymphocytes. B cells of adult peripheral or fetal cord blood transform with equal efficiency, whether assayed by DNA synthesis induction or by outgrowth of transformed lymphocytes. In contrast, unfractionated adult lymphocytes transform much less efficiently than those from fetal cord. Reconstitution experiments of different cell preparations indicated that this difference was due to a suppression of B-cell proliferation by adult Ig-negative lymphocytes which fetal Ig-negative lymphocytes were unable to perform. Separation of Ig-negative lymphocytes into various subpopulations revealed that the suppression was performed by T cells. Macrophages and null cells play little or no role in suppression. The relevance of this phenomenon to infection and recovery from EBV infection during and after infectious mononucleosis is discussed."}
{"id": "PMID:195005", "title": "The developmental cycle of Chlamydia trachomatis in McCoy cells treated with cytochalasin B.", "content": "The growth of a genital trachoma-inclusion conjunctivitis agent strain of Chlamydia trachomatis in McCoy cells treated with cytochalasin B was studied by quantitative infectivity estimations and by light and electron microscopy. Provided that infection of the monolayer was initiated by centrifuging the infectious particles on to the cells before incubation, this chlamydial strain grew as fast and to as high a titre [approximately 10(7) inclusion-forming units (i.f.u.) per culture] as those chlamydiae which infect cell cultures in vitro without centrifugation. Each i.f.u. inoculated yielded approximately 600 i.f.u., and extracellular infectivity was detected soon after intracellular infectivity appeared. Inclusions were recognized by fluorescent antibody staining techniques early in the developmental cycle when cultures were not infectious and when only reticulate bodies were seen by electron microscopy. Inclusions were recognized in Giemsa-stained preparations examined by dark ground microscopy only when elementary bodies appeared in the inclusions. Iodine staining was not a reliable indicator either of the number of inclusions present or of their infectivity.", "contents": "The developmental cycle of Chlamydia trachomatis in McCoy cells treated with cytochalasin B. The growth of a genital trachoma-inclusion conjunctivitis agent strain of Chlamydia trachomatis in McCoy cells treated with cytochalasin B was studied by quantitative infectivity estimations and by light and electron microscopy. Provided that infection of the monolayer was initiated by centrifuging the infectious particles on to the cells before incubation, this chlamydial strain grew as fast and to as high a titre [approximately 10(7) inclusion-forming units (i.f.u.) per culture] as those chlamydiae which infect cell cultures in vitro without centrifugation. Each i.f.u. inoculated yielded approximately 600 i.f.u., and extracellular infectivity was detected soon after intracellular infectivity appeared. Inclusions were recognized by fluorescent antibody staining techniques early in the developmental cycle when cultures were not infectious and when only reticulate bodies were seen by electron microscopy. Inclusions were recognized in Giemsa-stained preparations examined by dark ground microscopy only when elementary bodies appeared in the inclusions. Iodine staining was not a reliable indicator either of the number of inclusions present or of their infectivity."}
{"id": "PMID:195006", "title": "The uncoupled relationship between the temperature-sensitivity and neurovirulence in mice of mutants of vesicular stomatitis virus.", "content": "Inoculation of wild-type (wt) VSV intracerebrally (i.c.) in Swiss weanling mice results in a rapidly fatal illness with death in two to three days. In contrast, i.c. inoculation of temperature-sensitive (ts) VSV mutants G3I and G22, but not ts GII or ts G4I, results in a more slowly progressive central nervous system (CNS) disease with distinct neurological signs. Studies undertaken to evaluate the neurovirulence of ts VSV mutants indicated that the ability of ts mutants to produce pathological changes in the CNS of mice appeared related to their ability to replicate to high titre in brain and spinal cord. However, replication of ts VSV mutants in brain alone was not sufficient to produce clinical illness. More importantly, the ability of ts VSV mutants to replicate at non-permissive temperatures in vitro did not appear to correlate with neurovirulence. VSV harvests from brains and spinal cords of mice infected with each of the ts mutants were temperature-insensitive. In spite of their temperature-insensitivity, the biological behaviour of viruses recovered from CNS tissues was, surprisingly, not that which was characteristic of revertant clones. Virus isolates recovered from infected CNS tissues, despite their temperature-insensitivity, behaved biologically like the orignal stocks of ts mutant virus. These data suggest that temperature-sensitivity is not directly correlated with the unique pathogenesis elicited by infection with ts VSV mutants.", "contents": "The uncoupled relationship between the temperature-sensitivity and neurovirulence in mice of mutants of vesicular stomatitis virus. Inoculation of wild-type (wt) VSV intracerebrally (i.c.) in Swiss weanling mice results in a rapidly fatal illness with death in two to three days. In contrast, i.c. inoculation of temperature-sensitive (ts) VSV mutants G3I and G22, but not ts GII or ts G4I, results in a more slowly progressive central nervous system (CNS) disease with distinct neurological signs. Studies undertaken to evaluate the neurovirulence of ts VSV mutants indicated that the ability of ts mutants to produce pathological changes in the CNS of mice appeared related to their ability to replicate to high titre in brain and spinal cord. However, replication of ts VSV mutants in brain alone was not sufficient to produce clinical illness. More importantly, the ability of ts VSV mutants to replicate at non-permissive temperatures in vitro did not appear to correlate with neurovirulence. VSV harvests from brains and spinal cords of mice infected with each of the ts mutants were temperature-insensitive. In spite of their temperature-insensitivity, the biological behaviour of viruses recovered from CNS tissues was, surprisingly, not that which was characteristic of revertant clones. Virus isolates recovered from infected CNS tissues, despite their temperature-insensitivity, behaved biologically like the orignal stocks of ts mutant virus. These data suggest that temperature-sensitivity is not directly correlated with the unique pathogenesis elicited by infection with ts VSV mutants."}
{"id": "PMID:195007", "title": "Studies of L cells persistently infected with VSV: factors involved in the regulation of persistent infection.", "content": "Infection of interferon-treated L cells with VSV led frequently to the establishment of L cells persistently infected with VSV (LVSV cells). These cells were characterized by the following properties; (I) no supplement of antiviral factors such as anti-VSV antiserum, interferon, was required for their maintenance; (2) virus antigens were detected in about 5 to 30% of the cells by immunofluorescence staining; (3) the cells were not only resistant to superinfection by homologous virus, but also resistant to challenge by heterologous viruses such as Mengo virus; (4) the cells were destroyed by co-cultivation with heterologous cells susceptible to VSV infection; (5) the cells could be cured by serial cultivation in medium containing antiviral antibody, and the cured cells were as susceptible to VSV as normal L cells. It was shown that at least three factors (interferon, defective interfering [DI] particles and a selection of small-plaque temperature-sensitive [ts] mutants) took part in the maintenance of LVSV cells although it was difficult to evaluate exactly the relative importance of these factors. The effect of antiviral antibody, interferon and incubation temperature upon the maintenance of LVSV cells are discussed further.", "contents": "Studies of L cells persistently infected with VSV: factors involved in the regulation of persistent infection. Infection of interferon-treated L cells with VSV led frequently to the establishment of L cells persistently infected with VSV (LVSV cells). These cells were characterized by the following properties; (I) no supplement of antiviral factors such as anti-VSV antiserum, interferon, was required for their maintenance; (2) virus antigens were detected in about 5 to 30% of the cells by immunofluorescence staining; (3) the cells were not only resistant to superinfection by homologous virus, but also resistant to challenge by heterologous viruses such as Mengo virus; (4) the cells were destroyed by co-cultivation with heterologous cells susceptible to VSV infection; (5) the cells could be cured by serial cultivation in medium containing antiviral antibody, and the cured cells were as susceptible to VSV as normal L cells. It was shown that at least three factors (interferon, defective interfering [DI] particles and a selection of small-plaque temperature-sensitive [ts] mutants) took part in the maintenance of LVSV cells although it was difficult to evaluate exactly the relative importance of these factors. The effect of antiviral antibody, interferon and incubation temperature upon the maintenance of LVSV cells are discussed further."}
{"id": "PMID:195008", "title": "Biochemical mapping of the foot-and-mouth disease virus genome.", "content": "Four primary cleavage products, mol. wt. 10(3) X 100, 88, 56 and 52 (P100, P85, P56 and P52 respectively) are present in BHK 2I cells infected with foot-and-mouth disease virus (FMDV). However, no precursor polyprotein equal to the sum of their mol. wt. was detected, even when amino acid analogues and proteolytic enzyme inhibitors were used. Three of the primary products were shown to cleave to smaller polypeptides, including the capsid polypeptides of the virus. Polypeptide P88, which was shown to be the precursor of the capsid polypeptides, is translated from the gene located at the 5'-end of the genome. The order of the structural polypeptides, determined by the use of emetine, is VP4, VP2, VP3, VP1. The order of the remaining primary cleavage products is P52, P56 and P100. P56 is a stable product, identical with the virus infection associated (VIA) antigen found in virus harvests. The function of the other two products P52 and P100 is not known. EMDV thus differs from other picornaviruses in that there is an extra primary cleavage product, apparently resulting from translation of more of the virus genome.", "contents": "Biochemical mapping of the foot-and-mouth disease virus genome. Four primary cleavage products, mol. wt. 10(3) X 100, 88, 56 and 52 (P100, P85, P56 and P52 respectively) are present in BHK 2I cells infected with foot-and-mouth disease virus (FMDV). However, no precursor polyprotein equal to the sum of their mol. wt. was detected, even when amino acid analogues and proteolytic enzyme inhibitors were used. Three of the primary products were shown to cleave to smaller polypeptides, including the capsid polypeptides of the virus. Polypeptide P88, which was shown to be the precursor of the capsid polypeptides, is translated from the gene located at the 5'-end of the genome. The order of the structural polypeptides, determined by the use of emetine, is VP4, VP2, VP3, VP1. The order of the remaining primary cleavage products is P52, P56 and P100. P56 is a stable product, identical with the virus infection associated (VIA) antigen found in virus harvests. The function of the other two products P52 and P100 is not known. EMDV thus differs from other picornaviruses in that there is an extra primary cleavage product, apparently resulting from translation of more of the virus genome."}
{"id": "PMID:195009", "title": "Effects of interferon on vesicular stomatitis virus transcription and translation.", "content": "The effect of interferon on the synthesis of the RNA species and proteins of vesicular stomatitis virus has been studied in two cell types. Virus protein synthesis is inhibited by interferon despite the apparent presence of near normal amounts of virus RNA with sedimentation values characteristic of virus messenger RNA. The synthesis of those virus RNA species which are completely dependent on virus protein synthesis is preferentially inhibited in interferon-treated cells. These results are most consistent with a model of interferon action postulating a primary effect on translation of virus messenger RNA.", "contents": "Effects of interferon on vesicular stomatitis virus transcription and translation. The effect of interferon on the synthesis of the RNA species and proteins of vesicular stomatitis virus has been studied in two cell types. Virus protein synthesis is inhibited by interferon despite the apparent presence of near normal amounts of virus RNA with sedimentation values characteristic of virus messenger RNA. The synthesis of those virus RNA species which are completely dependent on virus protein synthesis is preferentially inhibited in interferon-treated cells. These results are most consistent with a model of interferon action postulating a primary effect on translation of virus messenger RNA."}
{"id": "PMID:195010", "title": "Multiplicity-dependent replication of varicella-zoster virus in interferon-treated cells.", "content": "The inhibitory effects of interferon (IF) on the replication of varicella-zoster (VZ) virus in human foreskin fibroblast (HFF) cultures inoculated with infected cells or with cell-free virus were assayed by measuring (1) yields of infected cells, (2) plaques, (3) microfoci and (4) cytopathic effects. More IF was needed to reduce yields of infected cells at high input multiplicities of challenge than at low input multiplicites, and still more IF was needed to prevent cytopathology due to VZ virus. A cell-free virus inoculum was more sensitive to the inhibitory effects of IF than an inoculum of infected cells. With the latter, but not with cell-free virus, the continuous presence of IF in the medium was necessary for it to express its maximum antiviral activity. To explain these results, it is suggested that some herpesviruses may establish \"reservoirs' of infectivity and thus provide a prolonged challenge to IF-treated cells which are not uniformly resistant to infection.", "contents": "Multiplicity-dependent replication of varicella-zoster virus in interferon-treated cells. The inhibitory effects of interferon (IF) on the replication of varicella-zoster (VZ) virus in human foreskin fibroblast (HFF) cultures inoculated with infected cells or with cell-free virus were assayed by measuring (1) yields of infected cells, (2) plaques, (3) microfoci and (4) cytopathic effects. More IF was needed to reduce yields of infected cells at high input multiplicities of challenge than at low input multiplicites, and still more IF was needed to prevent cytopathology due to VZ virus. A cell-free virus inoculum was more sensitive to the inhibitory effects of IF than an inoculum of infected cells. With the latter, but not with cell-free virus, the continuous presence of IF in the medium was necessary for it to express its maximum antiviral activity. To explain these results, it is suggested that some herpesviruses may establish \"reservoirs' of infectivity and thus provide a prolonged challenge to IF-treated cells which are not uniformly resistant to infection."}
{"id": "PMID:195011", "title": "Diurnal rhythms in cyclic nucleotide metabolism in Helix nervous system.", "content": "Concentrations of cAMP (cyclic adenosine 3',5'-monophosphate) and cGMP (cyclic guanosine 3',5'-monophosphate), in ganglia from the garden snail Helix pomatia, vary considerably over the course of the day. There is a maximum in the concentration of both cyclic nucleotides between 08:00 and 12:00 (lights on 06:00 to 18:00), with the cAMP maximum occurring slightly later than that in cGMP. In addition there can be several smaller maxima in cAMP and cGMP levels; the timing of these can be  markedly different from experiment to experiment, with cAMP and cGMP sometimes in and sometimes out of phase with each other. This pattern is observed in Helix which had been activated from the dormant state 4-6 days earlier, but is not present in dormant or in long-active animals. The cyclic nucleotide rhythm can be seen in ganglia maintained in organ culture, and persists for at least 24 hours after removal of the tissue from the animal. There appears to be little change in the level of basal or NaF-stimulated adenylate cyclase activity in Helix ganglia over the course of the day. On the other hand, both cAMP and cGMP phosphodiesterase activities exhibit rhythms which are consistent with the rhythms in cAMP and cGMP concentrations.", "contents": "Diurnal rhythms in cyclic nucleotide metabolism in Helix nervous system. Concentrations of cAMP (cyclic adenosine 3',5'-monophosphate) and cGMP (cyclic guanosine 3',5'-monophosphate), in ganglia from the garden snail Helix pomatia, vary considerably over the course of the day. There is a maximum in the concentration of both cyclic nucleotides between 08:00 and 12:00 (lights on 06:00 to 18:00), with the cAMP maximum occurring slightly later than that in cGMP. In addition there can be several smaller maxima in cAMP and cGMP levels; the timing of these can be  markedly different from experiment to experiment, with cAMP and cGMP sometimes in and sometimes out of phase with each other. This pattern is observed in Helix which had been activated from the dormant state 4-6 days earlier, but is not present in dormant or in long-active animals. The cyclic nucleotide rhythm can be seen in ganglia maintained in organ culture, and persists for at least 24 hours after removal of the tissue from the animal. There appears to be little change in the level of basal or NaF-stimulated adenylate cyclase activity in Helix ganglia over the course of the day. On the other hand, both cAMP and cGMP phosphodiesterase activities exhibit rhythms which are consistent with the rhythms in cAMP and cGMP concentrations."}
{"id": "PMID:195019", "title": "Inking in Aplysia californica. III. Two different synaptic conductance mechanisms for triggering central program for inking.", "content": "1. In the previous two papers we described the motor elements which mediate all-or-none inking behavior in Aplysia (4) and the contribution of specific membrane properties of the ink-gland motor cells to the central program for inking (5). In the present paper we show that the central program for inking (a characteristic accelerating burst of action potentials in the motor cells) can be triggered in two different ways: 1) by means of a suprathreshold stimulus delivered to a single site on the animal; and 2) by means of two subthreshold stimuli closely spaced in time, delivered either to the same or to different sites on the animal. 2. The single suprathreshold stimulus triggers the central program primarily by means of a complex increased-conductance EPSP. The two subthreshold stimuli trigger the program by means of a complex decreased-conductance EPSP which is capable of augmenting subsequent afferent synaptic input. 3. The synaptic augmentation produced by the decreased-conductance EPSP is attributable to two properties of the EPSP: 1) it increases the input resistance of the ink-gland motor cells so that the synaptic current from afferent input onto the cells produces larger, more effective EPSP's; and 2) it increases the electrotonic coupling among the motor cells, thereby producing increased positive feedback among them. Thus, the decreased-conductance EPSP provides a novel mechanism for spatial and temporal summation.", "contents": "Inking in Aplysia californica. III. Two different synaptic conductance mechanisms for triggering central program for inking. 1. In the previous two papers we described the motor elements which mediate all-or-none inking behavior in Aplysia (4) and the contribution of specific membrane properties of the ink-gland motor cells to the central program for inking (5). In the present paper we show that the central program for inking (a characteristic accelerating burst of action potentials in the motor cells) can be triggered in two different ways: 1) by means of a suprathreshold stimulus delivered to a single site on the animal; and 2) by means of two subthreshold stimuli closely spaced in time, delivered either to the same or to different sites on the animal. 2. The single suprathreshold stimulus triggers the central program primarily by means of a complex increased-conductance EPSP. The two subthreshold stimuli trigger the program by means of a complex decreased-conductance EPSP which is capable of augmenting subsequent afferent synaptic input. 3. The synaptic augmentation produced by the decreased-conductance EPSP is attributable to two properties of the EPSP: 1) it increases the input resistance of the ink-gland motor cells so that the synaptic current from afferent input onto the cells produces larger, more effective EPSP's; and 2) it increases the electrotonic coupling among the motor cells, thereby producing increased positive feedback among them. Thus, the decreased-conductance EPSP provides a novel mechanism for spatial and temporal summation."}
{"id": "PMID:195020", "title": "Peptidyl transferase activity in rat skeletal muscle ribosomes after protein restriction.", "content": "Rats were fed for 6 consecutive days a diet containing casein supplemented with 3 g/kg methionine. The protein level was either 20% or 3%. Skeletal muscle ribosomes were isolated and the activity of the ribosomal enzyme peptidyl transferase was determined. [3H]puromycin acted as acceptor for tRNA bound peptide provided it was located at the ribosomal peptidyl site. The results showed that the rate of peptidyl transferase activity was 13% lower after protein restriction. The differences amounted to 6% when diphtheria toxin and NAD were added as an inhibitor of elongation factor2. This factor catalyzes translocation of peptidyl-tRNA from ribosomal acceptor to peptidyl site. Between 0.11 and 0.15 pmoles peptidyl-tRNA per pmole ribosome were originally accessable as a substrate for peptidyl transferase. The results indicate that peptidyl transferase contributes to a decrease in protein  synthesis after protein restriction; but that other components also contribute to the decrease observed.", "contents": "Peptidyl transferase activity in rat skeletal muscle ribosomes after protein restriction. Rats were fed for 6 consecutive days a diet containing casein supplemented with 3 g/kg methionine. The protein level was either 20% or 3%. Skeletal muscle ribosomes were isolated and the activity of the ribosomal enzyme peptidyl transferase was determined. [3H]puromycin acted as acceptor for tRNA bound peptide provided it was located at the ribosomal peptidyl site. The results showed that the rate of peptidyl transferase activity was 13% lower after protein restriction. The differences amounted to 6% when diphtheria toxin and NAD were added as an inhibitor of elongation factor2. This factor catalyzes translocation of peptidyl-tRNA from ribosomal acceptor to peptidyl site. Between 0.11 and 0.15 pmoles peptidyl-tRNA per pmole ribosome were originally accessable as a substrate for peptidyl transferase. The results indicate that peptidyl transferase contributes to a decrease in protein  synthesis after protein restriction; but that other components also contribute to the decrease observed."}
{"id": "PMID:195023", "title": "Characterization of sterol carrier protein binding with 7-dehydrocholesterol and vitamin D3.", "content": "The interaction of rat liver sterol carrier protein (SCP) and 7-dehydrocholesterol or vitamin D3 was analyzed by the method of Scatchard plots and gel filtration on Sephadex G-100. Scatchard plots of binding data revealed that the binding behavior for 7-dehydrocholesterol was monophasic, while that for vitamin D3 was biphasic. In 7-dehydrocholesterol, the apparent number of binding sites and the apparent assocation constant K were 0.72 nmoles/mg protein and 8.75 X 10-7M-1, respectively. On the other hand, vitamin D3 showed two types of binding sites differing in affinity. The apparent number of binding sites and the K for high affinity binding were 0.65 nmoles/mg protein and 7.08 X 10-7M-1, those for low affinity binding were 1.51 nmoles/mg protein and 0.36 X 10-7M-1, respectively. Gel filtration of SCP on Sephadex G-100 column gave three protein peaks (peaks I, II and III protein according to the elution orders; Ve/Vo=1.0, 1.56 and 2.29, respectively). 7-Dehydrocholesterol was able to bind with peak III protein, while vitamin D3 was bound peaks II and III protein, respectively. The molecular weight of peak II protein was estimated to be 44,000 and that of peak III protein was 16,000. From these results, it was clearly demonstrated that SCP was involved in the transformation of 7-dehydrocholesterol to cholesterol and could also bind vitamin D3.", "contents": "Characterization of sterol carrier protein binding with 7-dehydrocholesterol and vitamin D3. The interaction of rat liver sterol carrier protein (SCP) and 7-dehydrocholesterol or vitamin D3 was analyzed by the method of Scatchard plots and gel filtration on Sephadex G-100. Scatchard plots of binding data revealed that the binding behavior for 7-dehydrocholesterol was monophasic, while that for vitamin D3 was biphasic. In 7-dehydrocholesterol, the apparent number of binding sites and the apparent assocation constant K were 0.72 nmoles/mg protein and 8.75 X 10-7M-1, respectively. On the other hand, vitamin D3 showed two types of binding sites differing in affinity. The apparent number of binding sites and the K for high affinity binding were 0.65 nmoles/mg protein and 7.08 X 10-7M-1, those for low affinity binding were 1.51 nmoles/mg protein and 0.36 X 10-7M-1, respectively. Gel filtration of SCP on Sephadex G-100 column gave three protein peaks (peaks I, II and III protein according to the elution orders; Ve/Vo=1.0, 1.56 and 2.29, respectively). 7-Dehydrocholesterol was able to bind with peak III protein, while vitamin D3 was bound peaks II and III protein, respectively. The molecular weight of peak II protein was estimated to be 44,000 and that of peak III protein was 16,000. From these results, it was clearly demonstrated that SCP was involved in the transformation of 7-dehydrocholesterol to cholesterol and could also bind vitamin D3."}
{"id": "PMID:195027", "title": "The identification of particulate matter in biological tissues and fluids.", "content": "Sections, 1-2 micron thick, of Araldite embedded tissue were prepared to provide a link between optical and electron microscopy for the identification of crystals. This technique permits examination of individual particles by means of polarising light microscopy, electron microscopy, X-ray energy spectroscopy and electron diffraction. It provides a reliable method for routine and research studies. It has led to the positive identification of individual crystals of calcium pyrophosphate dihydrate and hydroxyapatite in synovial fluids. The method can be applied to the identification of other particulate matter in a variety of biological specimens.", "contents": "The identification of particulate matter in biological tissues and fluids. Sections, 1-2 micron thick, of Araldite embedded tissue were prepared to provide a link between optical and electron microscopy for the identification of crystals. This technique permits examination of individual particles by means of polarising light microscopy, electron microscopy, X-ray energy spectroscopy and electron diffraction. It provides a reliable method for routine and research studies. It has led to the positive identification of individual crystals of calcium pyrophosphate dihydrate and hydroxyapatite in synovial fluids. The method can be applied to the identification of other particulate matter in a variety of biological specimens."}
{"id": "PMID:195028", "title": "Increased purine nucleotides in adenosine deaminase-deficient lymphocytes.", "content": "It was found that ATP and cyclic AMP were greatly increased in human blood lymphocytes which were deficient in ADA. Certain other purine and pyrimidine nucleotides were elevated but to a lesser degree. Energy production in these cells may be inhibited by the increase in nucleotides since the ATP:ADP ratio was significantly below normal. Thus it appears that the immunologic deficiency in human ADA deficiency is related to increased nucleotide concentrations in the lymphocytes.", "contents": "Increased purine nucleotides in adenosine deaminase-deficient lymphocytes. It was found that ATP and cyclic AMP were greatly increased in human blood lymphocytes which were deficient in ADA. Certain other purine and pyrimidine nucleotides were elevated but to a lesser degree. Energy production in these cells may be inhibited by the increase in nucleotides since the ATP:ADP ratio was significantly below normal. Thus it appears that the immunologic deficiency in human ADA deficiency is related to increased nucleotide concentrations in the lymphocytes."}
{"id": "PMID:195029", "title": "Vitamin D-resistant rickets associated with epidermal nevus syndrome: demonstration of a phosphaturic substance in the dermal lesions.", "content": "A 5-year-old boy was found to have severe rickets in association with hyperpigmented, linear, verrucous, epidermal tumors, typical of the epidermal nevus syndrome. Normocalcemia (9.6 mg/dl), hypophosphatemia (2.0 mg/dl), elevated serum alkaline phosphatase concentration (313 IU), decreased renal tubular reabsorption of phosphorus (35%), radiologic evidence of rickets, and lack of response to usual therapeutic doses of vitamin D suggested hypophosphatemic vitamin D-resistant rickets. Therapy with vitamin D in doses to 750,000 IU and oral phosphate, 2.0 gm/day, failed to induce healing of the rickets. A subtotal parathyroidectomy performed when the patient was 9 years old was also without effect. When he was 12 years old several fibroangiomas on the face and left lower limb were excised. Within three months all biochemical abnormalities resolved and radiologic evidence of healing was observed. A portion of excised tissue was homogenized and injection of the supernate into a 6-week-old puppy induced excessive phosphaturia. The data suggest that the rickets was induced by a phosphaturic substance extractable from the tumors.", "contents": "Vitamin D-resistant rickets associated with epidermal nevus syndrome: demonstration of a phosphaturic substance in the dermal lesions. A 5-year-old boy was found to have severe rickets in association with hyperpigmented, linear, verrucous, epidermal tumors, typical of the epidermal nevus syndrome. Normocalcemia (9.6 mg/dl), hypophosphatemia (2.0 mg/dl), elevated serum alkaline phosphatase concentration (313 IU), decreased renal tubular reabsorption of phosphorus (35%), radiologic evidence of rickets, and lack of response to usual therapeutic doses of vitamin D suggested hypophosphatemic vitamin D-resistant rickets. Therapy with vitamin D in doses to 750,000 IU and oral phosphate, 2.0 gm/day, failed to induce healing of the rickets. A subtotal parathyroidectomy performed when the patient was 9 years old was also without effect. When he was 12 years old several fibroangiomas on the face and left lower limb were excised. Within three months all biochemical abnormalities resolved and radiologic evidence of healing was observed. A portion of excised tissue was homogenized and injection of the supernate into a 6-week-old puppy induced excessive phosphaturia. The data suggest that the rickets was induced by a phosphaturic substance extractable from the tumors."}
{"id": "PMID:195030", "title": "Enteropathogens associated with pediatric diarrhea in Mexico City.", "content": "Enteropathogens were investigated as possible agents in pediatric diarrhea occurring in Mexico City during the summer of 1975. Pathogens were identified in 47 (76%) of 62 cases. Rotavirus particles were detected in 16 cases. Enterotoxigenic Escherichia coli was detected in 29 cases; 11 were positive for heat-labile enterotoxin and 18 were positive for only the heat-stable form of enterotoxin. Multiple pathogens were found simultaneously in 15 (24%) of the study population. This study indicates that the etiology of pediatric summertime diarrhea in Mexico City is diverse. ETEC and RV were the most frequently encountered pathogens, yet they frequently occurred together and with other pathogens. ST-only strains of toxigenic E. coli were as frequently recovered as LT-E. coli suggesting that both forms of ETEC must be sought in future field studies.", "contents": "Enteropathogens associated with pediatric diarrhea in Mexico City. Enteropathogens were investigated as possible agents in pediatric diarrhea occurring in Mexico City during the summer of 1975. Pathogens were identified in 47 (76%) of 62 cases. Rotavirus particles were detected in 16 cases. Enterotoxigenic Escherichia coli was detected in 29 cases; 11 were positive for heat-labile enterotoxin and 18 were positive for only the heat-stable form of enterotoxin. Multiple pathogens were found simultaneously in 15 (24%) of the study population. This study indicates that the etiology of pediatric summertime diarrhea in Mexico City is diverse. ETEC and RV were the most frequently encountered pathogens, yet they frequently occurred together and with other pathogens. ST-only strains of toxigenic E. coli were as frequently recovered as LT-E. coli suggesting that both forms of ETEC must be sought in future field studies."}
{"id": "PMID:195031", "title": "Clinical features of acute gastroenteritis associated with human reovirus-like agent in infants and young children.", "content": "Between January, 1974, and June, 1975, infection with a human reovirus-like agent was detected in 47% of 152 infants and children hospitalized with acute gastroenteritis. Certain epidemiologic, clinical, and laboratory findings appear to be helpful in distinguishing gastroenteritis due to HRVLA from other causes in those children sick enough to require hospitalization. Age: 76% of infants and children seven through 12 months of age and 76% of those 13 through 24 months of age had infection with the HRVLA, whereas such infection was found in only 21% of infants under six months of age and 23% of children 25 through 60 months of age. Time of Year: 61% of patients studied during the cooler months had HRVLA infection and such infection was not found from June to October. Frequency of vomiting and dehydration: Twice as many patients infected with HRVLA as those who were not had vomiting (92%) and significant dehydration (83%).", "contents": "Clinical features of acute gastroenteritis associated with human reovirus-like agent in infants and young children. Between January, 1974, and June, 1975, infection with a human reovirus-like agent was detected in 47% of 152 infants and children hospitalized with acute gastroenteritis. Certain epidemiologic, clinical, and laboratory findings appear to be helpful in distinguishing gastroenteritis due to HRVLA from other causes in those children sick enough to require hospitalization. Age: 76% of infants and children seven through 12 months of age and 76% of those 13 through 24 months of age had infection with the HRVLA, whereas such infection was found in only 21% of infants under six months of age and 23% of children 25 through 60 months of age. Time of Year: 61% of patients studied during the cooler months had HRVLA infection and such infection was not found from June to October. Frequency of vomiting and dehydration: Twice as many patients infected with HRVLA as those who were not had vomiting (92%) and significant dehydration (83%)."}
{"id": "PMID:195032", "title": "Parainfluenza viral infections in children: correlation of shedding with clinical manifestations.", "content": "Children presenting with acute respiratory disease to a private group practice in the fall of 1975 were studied to: (1) evaluate the efficacy in a pediatric office of a simple technics of obtaining nasal washes for the diagnosis of parainfluenza virus infections and (2) to determine the quantities of virus shed in relation to clinical characteristics. The nasal wash technic proved feasible for an office or clinic. Parainfluenza virus type 1 was recovered from 26 (74%) of 35 children with croup and from 40 (56%) of the total 72 children presenting with any form of respiratory illness. Virus was recovered significantly more often from children with croup and from those of younger age. The mean quantity of virus in 26 nasal washes was 2.97 log10 TCID50/ml. The shedding of greater quantities was correlated with younger age and the more frequent occurrence of laryngitis, pharyngitis, and fever.", "contents": "Parainfluenza viral infections in children: correlation of shedding with clinical manifestations. Children presenting with acute respiratory disease to a private group practice in the fall of 1975 were studied to: (1) evaluate the efficacy in a pediatric office of a simple technics of obtaining nasal washes for the diagnosis of parainfluenza virus infections and (2) to determine the quantities of virus shed in relation to clinical characteristics. The nasal wash technic proved feasible for an office or clinic. Parainfluenza virus type 1 was recovered from 26 (74%) of 35 children with croup and from 40 (56%) of the total 72 children presenting with any form of respiratory illness. Virus was recovered significantly more often from children with croup and from those of younger age. The mean quantity of virus in 26 nasal washes was 2.97 log10 TCID50/ml. The shedding of greater quantities was correlated with younger age and the more frequent occurrence of laryngitis, pharyngitis, and fever."}
{"id": "PMID:195034", "title": "Stannous-ion quantitation in pyrophosphate and polyphosphate radiopharmaceutical kits using differential pulse polarography.", "content": "Stannous salts are used as reducing agents in many radiopharmaceutical kits. Differential pulse polarography, with 1 M sulfuric acid as the supporting electrolyte, is a relatively simple and effective technique for stannous quantitation and can be used in the quality assurance testing of pyrophosphate and polyphosphate radiopharmaceutical kits.", "contents": "Stannous-ion quantitation in pyrophosphate and polyphosphate radiopharmaceutical kits using differential pulse polarography. Stannous salts are used as reducing agents in many radiopharmaceutical kits. Differential pulse polarography, with 1 M sulfuric acid as the supporting electrolyte, is a relatively simple and effective technique for stannous quantitation and can be used in the quality assurance testing of pyrophosphate and polyphosphate radiopharmaceutical kits."}
{"id": "PMID:195035", "title": "The pharmacokinetics of d-tubocurarine in man with and without renal failure.", "content": "Plasma and urine concentrations of d-tubocurarine (d-TC) were determined and twitch tension was monitored before and after the intravenous administration of d-TC, 0.5 mg/kg in patients anethetized with halothane and nitrous oxide with (N=5) and without (N=5) renal failure. Terminal half lives of d-TC of 231 and 330 minutes predicted from other studies for patients with and without renal function were consistent with plasma concentrations measured. In patients with normal renal function, 38% of unchanged d-TC was eliminated in urine in 25 hours as opposed to 13% in those patients with a newly transplanted kidney. However, we still conclude that a newly transplanted kidney can eliminate d-TC effectively since the kidney was inserted 3.5 hours after administration of d-TC. Absence of renal function significantly prolonged the duration of neuromuscular blockade but did not alter the plasma concentrations of d-TC required for neuromuscular blockade. Thus, prolonged neuromuscular blockade from d-TC in patients with renal failure is due to decreased elimination rate of the drug as a consequence of lack of renal function rather than increased sensitivity.", "contents": "The pharmacokinetics of d-tubocurarine in man with and without renal failure. Plasma and urine concentrations of d-tubocurarine (d-TC) were determined and twitch tension was monitored before and after the intravenous administration of d-TC, 0.5 mg/kg in patients anethetized with halothane and nitrous oxide with (N=5) and without (N=5) renal failure. Terminal half lives of d-TC of 231 and 330 minutes predicted from other studies for patients with and without renal function were consistent with plasma concentrations measured. In patients with normal renal function, 38% of unchanged d-TC was eliminated in urine in 25 hours as opposed to 13% in those patients with a newly transplanted kidney. However, we still conclude that a newly transplanted kidney can eliminate d-TC effectively since the kidney was inserted 3.5 hours after administration of d-TC. Absence of renal function significantly prolonged the duration of neuromuscular blockade but did not alter the plasma concentrations of d-TC required for neuromuscular blockade. Thus, prolonged neuromuscular blockade from d-TC in patients with renal failure is due to decreased elimination rate of the drug as a consequence of lack of renal function rather than increased sensitivity."}
{"id": "PMID:195033", "title": "Extraocular muscle surgery in the presence of complete paralysis of the fifth, sixth and seventh cranial nerves.", "content": "A nine-year-old boy developed paralytic left esotropia secondary to an intracranial lesion. He also exhibited total loss of function of the left fifth and seventh cranial nerves. Extraocular muscle surgery in this situation was felt to be dangerous to the operated eye. The degree of risk however could not be determined from published reports. Surgery was performed and was complicated by severe corneal ulceration. Use of a therapeutic contact lens presumedly helped in finally achieving a satisfactory result.", "contents": "Extraocular muscle surgery in the presence of complete paralysis of the fifth, sixth and seventh cranial nerves. A nine-year-old boy developed paralytic left esotropia secondary to an intracranial lesion. He also exhibited total loss of function of the left fifth and seventh cranial nerves. Extraocular muscle surgery in this situation was felt to be dangerous to the operated eye. The degree of risk however could not be determined from published reports. Surgery was performed and was complicated by severe corneal ulceration. Use of a therapeutic contact lens presumedly helped in finally achieving a satisfactory result."}
{"id": "PMID:195037", "title": "Mechanism of cardiovascular effects of clonidine in conscious and anesthetized rabbits.", "content": "The actions of intravenous clonidine [2-(2,6 dichlorophenylamino)-2-imidazoline hydrochloride] on blood pressure and heart rate were examined in conscious rabbits. Complete transection of thecervical spinal cord increased the intensity and duration of the hypertensive effect of 30 microgram/kg of clonidine and completely abolished the fall in blood pressure. Heart rate slowing by clonidine was reduced. Result were similar 1 hour, 24 hours and 7 days after cord transection. Bilateral aortic sinus nerve section (baroreceptor deafferentation) increased both the hypertensive and hypotensive action of clonidine but reduced the bradycardia. When cervical cord transection was combined with batensive action, were abolished. We conclude that whereas the hypertensive action results from a direct effect on peripheral adrenoceptors, the fall in blood pressure is related to a reduction in sympathetic tone mediated at the level of the brain stem or more rostrally. The heart rate slowing results from both a reduction in sympathetic tone and also an enhanced vagal outflow. The increase in vagal tone seems to be dependent on the intergrity of baroreceptor afferent pathways.", "contents": "Mechanism of cardiovascular effects of clonidine in conscious and anesthetized rabbits. The actions of intravenous clonidine [2-(2,6 dichlorophenylamino)-2-imidazoline hydrochloride] on blood pressure and heart rate were examined in conscious rabbits. Complete transection of thecervical spinal cord increased the intensity and duration of the hypertensive effect of 30 microgram/kg of clonidine and completely abolished the fall in blood pressure. Heart rate slowing by clonidine was reduced. Result were similar 1 hour, 24 hours and 7 days after cord transection. Bilateral aortic sinus nerve section (baroreceptor deafferentation) increased both the hypertensive and hypotensive action of clonidine but reduced the bradycardia. When cervical cord transection was combined with batensive action, were abolished. We conclude that whereas the hypertensive action results from a direct effect on peripheral adrenoceptors, the fall in blood pressure is related to a reduction in sympathetic tone mediated at the level of the brain stem or more rostrally. The heart rate slowing results from both a reduction in sympathetic tone and also an enhanced vagal outflow. The increase in vagal tone seems to be dependent on the intergrity of baroreceptor afferent pathways."}
{"id": "PMID:195039", "title": "Inhibition of canine adrenergic transmission by an analog of dopamine: GJH-166.", "content": "Experiments were conducted to investigate the effect of GJH-166 [Trans-4-methyl-7,8-dihydroxy-1,2,3,4,4a,5,6,10b-octahydrobenzo (f) quinoline HBr], a potential dopamine agonist, on responses to adrenergic vasoconstrictor stimuli in dogs. The hindlimb, gracilis muscle and spleen were isolated and perfused with arterial blood at constant flows. Responses of the nictitating membrane to adrenergic stimuli were aso studied. Intravenous injections of GJH-166 in doses of 0.25 to 4.00 micron/kg impaired responses to sympathetic nerve stimulation of the perfused hindlimb, gacilis muscle and spleen, and also inhibited responses of the nictitating membrane. GJH-166 had a preferential inhibitory effect on responses induced by low frequency stimulation of nerves. Haloperidol antagonized the inhibitory effect of GJH-166 on sympathetic transmission. The changes induced by norepinephrine at the perfused sites were not affected by the compound. Pressor responses to norepinephrine and tyramine were not inhibited by GJH-166. As a result of this study, the suggestion has been made that GJH-166 impairs sympathetic transmission by acting on certain inhibitory dopaminergic receptors located on the adrenergic nerve terminals.", "contents": "Inhibition of canine adrenergic transmission by an analog of dopamine: GJH-166. Experiments were conducted to investigate the effect of GJH-166 [Trans-4-methyl-7,8-dihydroxy-1,2,3,4,4a,5,6,10b-octahydrobenzo (f) quinoline HBr], a potential dopamine agonist, on responses to adrenergic vasoconstrictor stimuli in dogs. The hindlimb, gracilis muscle and spleen were isolated and perfused with arterial blood at constant flows. Responses of the nictitating membrane to adrenergic stimuli were aso studied. Intravenous injections of GJH-166 in doses of 0.25 to 4.00 micron/kg impaired responses to sympathetic nerve stimulation of the perfused hindlimb, gacilis muscle and spleen, and also inhibited responses of the nictitating membrane. GJH-166 had a preferential inhibitory effect on responses induced by low frequency stimulation of nerves. Haloperidol antagonized the inhibitory effect of GJH-166 on sympathetic transmission. The changes induced by norepinephrine at the perfused sites were not affected by the compound. Pressor responses to norepinephrine and tyramine were not inhibited by GJH-166. As a result of this study, the suggestion has been made that GJH-166 impairs sympathetic transmission by acting on certain inhibitory dopaminergic receptors located on the adrenergic nerve terminals."}
{"id": "PMID:195041", "title": "Termination of transmitter release by stimulation of sodium-potassium activated ATPase.", "content": "1. The release of acetylcholine (ACh) from Auerbach's plexus of guinea-pig ileum has been measured in eserinized Krebs solution using longitudinal muscle strip preparations. 2. Removal of the external K ions enhanced both the resting and stimulated release of ACh from the plexus. This effect was not affected by tetrodotoxin. 3. On readmission of K+ to tissues which had been suspended in K-free Krebs solution the release of ACh was promptly reduced in both stimulated and unstimulated tissues. The extent of the reduction of ACh release depended on the exposure time to K-free solution, the recovery being delayed by longer exposure. 4. The ACh releasing effect of (1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) was completely inhibited by the readmission of K ions to tissue which had been kept in K-free Krebs solution. 5. Rb+ substitution for K+ produced no change in ACh release and addition of 5-9 mM-Rb after K removal reduced the release of ACh as K did readmission. When the K ions were substituted by Cs+, both the resting and stimulated release were enhanced. The amount of ACh released by a stimulus was enhanced both at low and high frequency of sustained stimulation. 6. Removal of the external K ions increased the release of tritiated noradrenaline (NA), from isolated rat iris; however, when K+ (5-9 mM) was readmitted the release was reduced even below the control value. 7. It is concluded that the stimulation of (Na+-K+)-activated ATP-ase in the membrane inhibits the release of transmitter, and under physiological condition Ca-fluxes and the subsequent inhibition of membrane ATP-ase may be involved in triggering the release of transmitter.", "contents": "Termination of transmitter release by stimulation of sodium-potassium activated ATPase. 1. The release of acetylcholine (ACh) from Auerbach's plexus of guinea-pig ileum has been measured in eserinized Krebs solution using longitudinal muscle strip preparations. 2. Removal of the external K ions enhanced both the resting and stimulated release of ACh from the plexus. This effect was not affected by tetrodotoxin. 3. On readmission of K+ to tissues which had been suspended in K-free Krebs solution the release of ACh was promptly reduced in both stimulated and unstimulated tissues. The extent of the reduction of ACh release depended on the exposure time to K-free solution, the recovery being delayed by longer exposure. 4. The ACh releasing effect of (1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) was completely inhibited by the readmission of K ions to tissue which had been kept in K-free Krebs solution. 5. Rb+ substitution for K+ produced no change in ACh release and addition of 5-9 mM-Rb after K removal reduced the release of ACh as K did readmission. When the K ions were substituted by Cs+, both the resting and stimulated release were enhanced. The amount of ACh released by a stimulus was enhanced both at low and high frequency of sustained stimulation. 6. Removal of the external K ions increased the release of tritiated noradrenaline (NA), from isolated rat iris; however, when K+ (5-9 mM) was readmitted the release was reduced even below the control value. 7. It is concluded that the stimulation of (Na+-K+)-activated ATP-ase in the membrane inhibits the release of transmitter, and under physiological condition Ca-fluxes and the subsequent inhibition of membrane ATP-ase may be involved in triggering the release of transmitter."}
{"id": "PMID:195042", "title": "The effects of strontium and barium ions at synapses in sympathetic ganglia.", "content": "1. A study has been made of the effects of Sr2+ and Ba2+ ions at synapses in isolated superior cervical ganglia of guinea-pigs. Intracellular recordings of membrane potential were made from ganglion cells in the presence of different concentrations of Ca2+, Sr2+ and Ba2+ ions. 2. The addition of Sr2+ (2-5 mM) caused little change in resting membrane potential; in contrast, Ba2+ (1-6 mM) always depolarized the cells and prolonged the duration of action potentials. 3. The resting frequency of spontaneous miniature excitatory post-synaptic potentials (min. e.p.s.p.s) was briefly accelerated by the addition of either Sr2+ or Ba2+, but subsequently returned to about control levels. 4. Following replacement of Ca2+ by Sr2+, e.p.s.p.s could always be evoked during repetitive stimulation of preganglionic axons at a fixed latency after the nerve impulses ('phasic' transmitter release). Replacement of Ca2+ by Ba2+ produced many asynchronous e.p.s.p.s during trains of impulses ('residual' transmitter release). 5. By analysis of the interaction between Sr2+ and Ca2+, Sr2+ was shown to have a partial agonist action on 'phasic' transmitter release. The same analysis applied to Ba2+ failed to demonstrate either a partial agonist or antagonist action. 6. Both Sr2+ and Ba2+ prolonged e.p.s.p.s. Changes in Sr2+ could mainly be attributed to its effect on cell input resistance; Ba2+ may also prolong the time course of transmitter release. 7. The increased frequency of min. e.p.s.p.s which occurs during repetitive stimulation was potentiated by both Sr2+ and Ba2+, Ba2+ being about twice as potent as Sr2+. This activation of 'residual' transmitter release is independent of the action of these ions on 'phasic' release. 8. It is concluded that the reported maintenance by Ba2+ of acetyl-choline output from perfused ganglia results from the asynchronous release of large numbers of quanta during trains of impulses.", "contents": "The effects of strontium and barium ions at synapses in sympathetic ganglia. 1. A study has been made of the effects of Sr2+ and Ba2+ ions at synapses in isolated superior cervical ganglia of guinea-pigs. Intracellular recordings of membrane potential were made from ganglion cells in the presence of different concentrations of Ca2+, Sr2+ and Ba2+ ions. 2. The addition of Sr2+ (2-5 mM) caused little change in resting membrane potential; in contrast, Ba2+ (1-6 mM) always depolarized the cells and prolonged the duration of action potentials. 3. The resting frequency of spontaneous miniature excitatory post-synaptic potentials (min. e.p.s.p.s) was briefly accelerated by the addition of either Sr2+ or Ba2+, but subsequently returned to about control levels. 4. Following replacement of Ca2+ by Sr2+, e.p.s.p.s could always be evoked during repetitive stimulation of preganglionic axons at a fixed latency after the nerve impulses ('phasic' transmitter release). Replacement of Ca2+ by Ba2+ produced many asynchronous e.p.s.p.s during trains of impulses ('residual' transmitter release). 5. By analysis of the interaction between Sr2+ and Ca2+, Sr2+ was shown to have a partial agonist action on 'phasic' transmitter release. The same analysis applied to Ba2+ failed to demonstrate either a partial agonist or antagonist action. 6. Both Sr2+ and Ba2+ prolonged e.p.s.p.s. Changes in Sr2+ could mainly be attributed to its effect on cell input resistance; Ba2+ may also prolong the time course of transmitter release. 7. The increased frequency of min. e.p.s.p.s which occurs during repetitive stimulation was potentiated by both Sr2+ and Ba2+, Ba2+ being about twice as potent as Sr2+. This activation of 'residual' transmitter release is independent of the action of these ions on 'phasic' release. 8. It is concluded that the reported maintenance by Ba2+ of acetyl-choline output from perfused ganglia results from the asynchronous release of large numbers of quanta during trains of impulses."}
{"id": "PMID:195043", "title": "Muscarinic, alpha-adrenergic and peptide receptors regulate the same calcium influx sites in the parotid gland.", "content": "1. Carbachol, phenylephrine and substance P were each capable of producing a transient release of K (86 Rb) from rat parotid slices in the absence of extracellular Ca. 2. Each of the agonists was also capable of producing \"cross-receptor inactivation\"; that is, if a transient response was elicited by any one of the agonists then no transient response could be obtained by either of the other two. 3. Removal of carbachol from muscarinic receptors with atropine did not reverse the cross-receptor inactivation of the substance P response unless Ca was added with substance P or unless Ca was present when atropine was added. 4. It is concluded that the K release response in the parotid gland is mediated by receptor-controlled Ca influx sites. These influx sites also bind Ca at a location inaccessible to EGTA and release the bound Ca upon receptor activation. 5. It is also conlcuded that all three receptors (muscarinic, alpha-adrenergic, and peptide) appear to regulate the same Ca influx sites.", "contents": "Muscarinic, alpha-adrenergic and peptide receptors regulate the same calcium influx sites in the parotid gland. 1. Carbachol, phenylephrine and substance P were each capable of producing a transient release of K (86 Rb) from rat parotid slices in the absence of extracellular Ca. 2. Each of the agonists was also capable of producing \"cross-receptor inactivation\"; that is, if a transient response was elicited by any one of the agonists then no transient response could be obtained by either of the other two. 3. Removal of carbachol from muscarinic receptors with atropine did not reverse the cross-receptor inactivation of the substance P response unless Ca was added with substance P or unless Ca was present when atropine was added. 4. It is concluded that the K release response in the parotid gland is mediated by receptor-controlled Ca influx sites. These influx sites also bind Ca at a location inaccessible to EGTA and release the bound Ca upon receptor activation. 5. It is also conlcuded that all three receptors (muscarinic, alpha-adrenergic, and peptide) appear to regulate the same Ca influx sites."}
{"id": "PMID:195050", "title": "Changes in attitudes about mental illness among nursing students following a psychiatric affiliation.", "content": "The purpose of this study was to determine changes in nursing students' attitudes about mental illness following a twelve-week psychiatric affiliation program in a state mental hospital. Data were collected by means of two combined opinions about mental illness scales -- Cohen and Struening's factor analytically-derived Opinions About Mental Illness (OMI) questionnaire and Ellsworth's empirically-derived Opinions About Mental Illness Scale. The sample consisted of 95 student nurses from three diploma schools of nursing. The subjects were administered the instrument at the beginning and end of their psychiatric affiliation. Following the affiliation, student nurses' attitudes about mental illness changed significantly in a favorable direction on the following attitudinal dimensions: Authoritarianism, Mental Hygiene Ideology, Social Restrictiveness, Interpersonal Etiology, Nontraditionalism, and Restrictive Control. Although significant changes were not found on Benevolence and Protective Benevolence, there was a trend toward favorable changes on both attitudinal dimensions.", "contents": "Changes in attitudes about mental illness among nursing students following a psychiatric affiliation. The purpose of this study was to determine changes in nursing students' attitudes about mental illness following a twelve-week psychiatric affiliation program in a state mental hospital. Data were collected by means of two combined opinions about mental illness scales -- Cohen and Struening's factor analytically-derived Opinions About Mental Illness (OMI) questionnaire and Ellsworth's empirically-derived Opinions About Mental Illness Scale. The sample consisted of 95 student nurses from three diploma schools of nursing. The subjects were administered the instrument at the beginning and end of their psychiatric affiliation. Following the affiliation, student nurses' attitudes about mental illness changed significantly in a favorable direction on the following attitudinal dimensions: Authoritarianism, Mental Hygiene Ideology, Social Restrictiveness, Interpersonal Etiology, Nontraditionalism, and Restrictive Control. Although significant changes were not found on Benevolence and Protective Benevolence, there was a trend toward favorable changes on both attitudinal dimensions."}
{"id": "PMID:195053", "title": "Porcine respiratory disease in the western Cape Province.", "content": "The aetiology and pathogenesis of respiratory syndromes in pigs are reviewed with emphasis on the role of environmental factors and diagnosis. Therapeutic and control measures are suggested and the cost of various regimens is dealt with in detail.", "contents": "Porcine respiratory disease in the western Cape Province. The aetiology and pathogenesis of respiratory syndromes in pigs are reviewed with emphasis on the role of environmental factors and diagnosis. Therapeutic and control measures are suggested and the cost of various regimens is dealt with in detail."}
{"id": "PMID:195054", "title": "Antiviral activity of some beta-diketones. 1. Aryl alkyl diketones. In vitro activity against both RNA and DNA viruses.", "content": "The discovery that 4-[3-ethyl-6-[(3,4-methylenedioxy)phenyl]-3-hexenyl]-3,5-heptanedione (40) exhibited an in vitro inhibitory effect against equine rhinovirus led to a structure--activity study to establish the criteria for optimum activity. Modification of the bridge included removal of the ethyl group and reduction of the double bond. The heptanedione was replaced with hexanedione and pentanedione with a minimal effect. The effect of replacing the heptanedione with beta-keto esters and monoketones was also investigated. Maintaining the hexamethylene bridge and heptanedione, the methylenedioxy group was replaced with various substitutents. In general, most substituents did not adversely affect activity particularly against equine rhinovirus although there was some variation in activity against herpesvirus. Strongly hydrophilic groups significantly reduced activity. Finally, the effect of varying the length of the alkyl bridge was examined in the 4-hydroxyphenyl series, where peak activity was attained with n = 8.", "contents": "Antiviral activity of some beta-diketones. 1. Aryl alkyl diketones. In vitro activity against both RNA and DNA viruses. The discovery that 4-[3-ethyl-6-[(3,4-methylenedioxy)phenyl]-3-hexenyl]-3,5-heptanedione (40) exhibited an in vitro inhibitory effect against equine rhinovirus led to a structure--activity study to establish the criteria for optimum activity. Modification of the bridge included removal of the ethyl group and reduction of the double bond. The heptanedione was replaced with hexanedione and pentanedione with a minimal effect. The effect of replacing the heptanedione with beta-keto esters and monoketones was also investigated. Maintaining the hexamethylene bridge and heptanedione, the methylenedioxy group was replaced with various substitutents. In general, most substituents did not adversely affect activity particularly against equine rhinovirus although there was some variation in activity against herpesvirus. Strongly hydrophilic groups significantly reduced activity. Finally, the effect of varying the length of the alkyl bridge was examined in the 4-hydroxyphenyl series, where peak activity was attained with n = 8."}
{"id": "PMID:195055", "title": "Antiviral activity of some beta-diketones. 2. Aryloxy alkyl diketones. In vitro activity against both RNA and DNA viruses.", "content": "A series of aryloxy alkyl diketones II was synthesized and screened in vitro for antiviral activity. The effect of various substituents on the phenyl ring, as well as the length of the alkyl bridge, was examined to establish the requirements for optimum activity. One of the most active members of the series, 4-[6-(2-chloro-4-methoxy)phenoxy]hexyl-3,5-heptanedione (56), exhibited a high level of activity against both DNA and RNA viruses in both the tissue culture and organ culture screens and was particularly effective against herpesvirus type 1 and 2.", "contents": "Antiviral activity of some beta-diketones. 2. Aryloxy alkyl diketones. In vitro activity against both RNA and DNA viruses. A series of aryloxy alkyl diketones II was synthesized and screened in vitro for antiviral activity. The effect of various substituents on the phenyl ring, as well as the length of the alkyl bridge, was examined to establish the requirements for optimum activity. One of the most active members of the series, 4-[6-(2-chloro-4-methoxy)phenoxy]hexyl-3,5-heptanedione (56), exhibited a high level of activity against both DNA and RNA viruses in both the tissue culture and organ culture screens and was particularly effective against herpesvirus type 1 and 2."}
{"id": "PMID:195056", "title": "Thyroxine analogues. 23. Quantitative structure-activity correlation studies of in vivo and in vitro thyromimetic activities.", "content": "Quantitative structure-activity correlation studies of thyroid hormone analogues have been utilized to examine (1) in vivo rat antigoiter activities; (2) in vitro binding affinities to intact rat hepatic nuclei, solubilized rat hepatic nuclear protein receptors, and the plasma protein thyroxine binding globulin; and (3) correlations between in vivo antigoiter activities and in vitro binding to nuclear receptors. These studies provide a more precise elucidation of the relative importance of the physiochemical factors which influence thyromimetic activities. In particular, they (1) provide the first systematic QSAR examination of drug-receptor interactions and of the dependence of in vivo activity on such interactions; (2) demonstrate the importance of the interactive effects of the 3' and 5' substituents and of the 4'-OH with each other as well as with nuclear receptors in influencing binding affinity; (3) support the hypothesis that binding to nuclear receptors is the first step in initiating the events which lead to subsequent hormonal expression; (4) show that the free energy of binding to nuclear receptors can be factored into the contributing physicochemical properties of the substituents; and (5) suggest factors that need to be considered in designing new analogues.", "contents": "Thyroxine analogues. 23. Quantitative structure-activity correlation studies of in vivo and in vitro thyromimetic activities. Quantitative structure-activity correlation studies of thyroid hormone analogues have been utilized to examine (1) in vivo rat antigoiter activities; (2) in vitro binding affinities to intact rat hepatic nuclei, solubilized rat hepatic nuclear protein receptors, and the plasma protein thyroxine binding globulin; and (3) correlations between in vivo antigoiter activities and in vitro binding to nuclear receptors. These studies provide a more precise elucidation of the relative importance of the physiochemical factors which influence thyromimetic activities. In particular, they (1) provide the first systematic QSAR examination of drug-receptor interactions and of the dependence of in vivo activity on such interactions; (2) demonstrate the importance of the interactive effects of the 3' and 5' substituents and of the 4'-OH with each other as well as with nuclear receptors in influencing binding affinity; (3) support the hypothesis that binding to nuclear receptors is the first step in initiating the events which lead to subsequent hormonal expression; (4) show that the free energy of binding to nuclear receptors can be factored into the contributing physicochemical properties of the substituents; and (5) suggest factors that need to be considered in designing new analogues."}
{"id": "PMID:195057", "title": "Synthesis, structure, and reactivity of adenosine cyclic 3',5'-phosphate benzyl triesters.", "content": "A series of triesters of adenosine cyclic 3',5'-phosphate was synthesized by treatment of the free acid with various diazoalkanes (R=H, CH3, C6H5,0-NO2C6H4, p-NO2C6H4, p-CH3C6H4). The resulting diastereomeric mixtures were separated into their axial and equatorial components. Hydrolysis of the compounds was examined as well as photolysis of the photolabile o-nitrobenzyl ester. All compounds were then tested for their ability to activate the cAMP-dependent protein kinase and for their ability to serve as a substrate for the cAMP phosphodiesterase showing almost no effect on either enzyme. In a biological assay the benzyl triesters were able to penetrate into C 6 rat glioma cells and to induce the typical morphological alteration of the cell shape known for high cellular levels of cAMP. It was concluded that the benzyl triesters of cAMP are useful derivatives which can be efficiently and specifically converted to the parent nucleotide. Benzyl derivatives of biologically active phosphodiesters may provide a useful tool for study in biology and pharmacology.", "contents": "Synthesis, structure, and reactivity of adenosine cyclic 3',5'-phosphate benzyl triesters. A series of triesters of adenosine cyclic 3',5'-phosphate was synthesized by treatment of the free acid with various diazoalkanes (R=H, CH3, C6H5,0-NO2C6H4, p-NO2C6H4, p-CH3C6H4). The resulting diastereomeric mixtures were separated into their axial and equatorial components. Hydrolysis of the compounds was examined as well as photolysis of the photolabile o-nitrobenzyl ester. All compounds were then tested for their ability to activate the cAMP-dependent protein kinase and for their ability to serve as a substrate for the cAMP phosphodiesterase showing almost no effect on either enzyme. In a biological assay the benzyl triesters were able to penetrate into C 6 rat glioma cells and to induce the typical morphological alteration of the cell shape known for high cellular levels of cAMP. It was concluded that the benzyl triesters of cAMP are useful derivatives which can be efficiently and specifically converted to the parent nucleotide. Benzyl derivatives of biologically active phosphodiesters may provide a useful tool for study in biology and pharmacology."}
{"id": "PMID:195058", "title": "Improved synthesis and in vitro antiviral activities of 5-cyanouridine and 5-cyano-2'-deoxyuridine.", "content": "In order to evaluate the influence of the cyano group on the antiviral activity of pyrimidine deoxyribonucleosides, a moderate yield, unified approach to the synthesis of both 5-cyanouridine and 5-cyano-2'-deoxyuridine was developed. Thus, treatment of the appropriate acetylated 5-bromouracil nucleoside with NaCN or KCN in Me2SO at 90-110 degrees C gave, after deblocking, 35-45% yields of the corresponding 5-cyanouracil nucleosides. 5-Cyanouridine was devoid of significant activity against vaccinia virus, herpes simplex-1, and vesicular stomatitis virus, but 5-cyano-2'-deoxyuridine, while lacking activity against herpes simplex, showed significant inhibition of vaccina virus; for instance, 5-cyano-2'-deoxyuridine inhibited vaccinia virus replication at concentrations 10-20 times that required for inhibition by the known antivirals, 5-iodo-2'-deoxyuridine and 1-(beta-D-arabinofuranosyl)adenine. Replacement of the 5-halogeno substituents of pyrimidine deoxyribonucleosides thus decreases, but does not abolish, antiviral activity.", "contents": "Improved synthesis and in vitro antiviral activities of 5-cyanouridine and 5-cyano-2'-deoxyuridine. In order to evaluate the influence of the cyano group on the antiviral activity of pyrimidine deoxyribonucleosides, a moderate yield, unified approach to the synthesis of both 5-cyanouridine and 5-cyano-2'-deoxyuridine was developed. Thus, treatment of the appropriate acetylated 5-bromouracil nucleoside with NaCN or KCN in Me2SO at 90-110 degrees C gave, after deblocking, 35-45% yields of the corresponding 5-cyanouracil nucleosides. 5-Cyanouridine was devoid of significant activity against vaccinia virus, herpes simplex-1, and vesicular stomatitis virus, but 5-cyano-2'-deoxyuridine, while lacking activity against herpes simplex, showed significant inhibition of vaccina virus; for instance, 5-cyano-2'-deoxyuridine inhibited vaccinia virus replication at concentrations 10-20 times that required for inhibition by the known antivirals, 5-iodo-2'-deoxyuridine and 1-(beta-D-arabinofuranosyl)adenine. Replacement of the 5-halogeno substituents of pyrimidine deoxyribonucleosides thus decreases, but does not abolish, antiviral activity."}
{"id": "PMID:195059", "title": "Agonist effects of beta-phenethylamines on the noradrenergic cyclic adenosine 3',5'-monophosphate generating system in rat limbic forebrain. Stereoisomers of p-hydroxynorephedrine.", "content": "Significant agonist activity for the specific noradrenergic cyclic adenosine 3',5'-monophosphate (cAMP) generating system in rat limbic forebrain requires a beta-3,4-dihydroxyphenethylamine with a beta-hydroxyl group in the R configuration. Thus, neither of the enantiomers of p-hydroxynorephedrine nor of p-hydroxynorpseudoephedrine mimics the agonist activity of (R)-norepinephrine. It has yet to be established whether or not one of the p-hydroxynorephedrines exhibits antagonist activity in this same system.", "contents": "Agonist effects of beta-phenethylamines on the noradrenergic cyclic adenosine 3',5'-monophosphate generating system in rat limbic forebrain. Stereoisomers of p-hydroxynorephedrine. Significant agonist activity for the specific noradrenergic cyclic adenosine 3',5'-monophosphate (cAMP) generating system in rat limbic forebrain requires a beta-3,4-dihydroxyphenethylamine with a beta-hydroxyl group in the R configuration. Thus, neither of the enantiomers of p-hydroxynorephedrine nor of p-hydroxynorpseudoephedrine mimics the agonist activity of (R)-norepinephrine. It has yet to be established whether or not one of the p-hydroxynorephedrines exhibits antagonist activity in this same system."}
{"id": "PMID:195065", "title": "Cyclic nucleotide levels in mouse mammary epithelial cells during growth arrest and growth initiation in culture.", "content": "Intracellular levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) were measured in high and low tumorigenic mouse mammary epithelial cells during growth arrest in 1% fetal bovine serum and during the first 60 minutes after serum stimulation of cell proliferation in arrested cultures. Stationary MCG-T14 cells, which are highly tumorigenic and grow to high densities in 1% serum, exhibited lower levels of cAMP, higher levels of cGMP, and a lower ratio of cAMP to cGMP than quiescent MCG-V14 cells, which have low tumorigenicity and achieve low cell densities in 1% serum. Within 5-10 minutes after cell growth was initiated in arrested cultures by the addition of serum, both cell lines responded with a fourfold to fivefold increase in cGMP and a concomitant 50% decrease in cAMP. MCG-T14 cells exhibited the highest intracellular levels of cGMP and the lowest cAMP to cGMP ratio within 10 minutes after serum addition.", "contents": "Cyclic nucleotide levels in mouse mammary epithelial cells during growth arrest and growth initiation in culture. Intracellular levels of cyclic AMP (cAMP) and cyclic GMP (cGMP) were measured in high and low tumorigenic mouse mammary epithelial cells during growth arrest in 1% fetal bovine serum and during the first 60 minutes after serum stimulation of cell proliferation in arrested cultures. Stationary MCG-T14 cells, which are highly tumorigenic and grow to high densities in 1% serum, exhibited lower levels of cAMP, higher levels of cGMP, and a lower ratio of cAMP to cGMP than quiescent MCG-V14 cells, which have low tumorigenicity and achieve low cell densities in 1% serum. Within 5-10 minutes after cell growth was initiated in arrested cultures by the addition of serum, both cell lines responded with a fourfold to fivefold increase in cGMP and a concomitant 50% decrease in cAMP. MCG-T14 cells exhibited the highest intracellular levels of cGMP and the lowest cAMP to cGMP ratio within 10 minutes after serum addition."}
{"id": "PMID:195066", "title": "Tissue-specific antibodies against human lung and breast carcinoma dehistonized chromatins.", "content": "Tissue-specific antisera against human lung and breast carcinoma dehistonized chromatins were obtained. The specificity of these antisera was determined by complement fixation. In the presence of antiserum against human lung carcinoma, only chromatins from lung carcinoma fixed complement significantly, whereas chromatins isolated from human breast carcinoma, HeLa cells, normal lung tissue, breast tissue, or term placenta were negative (i.e., inactive). In a similar assay with the use of antiserum against dehistonized breast carcinoma chromatins, only breast carcinoma chromatins fixed complement. Immunohistochemical localization of the antigens by the horseradish peroxidase bridge method demonstrated their presence in the nuclei.", "contents": "Tissue-specific antibodies against human lung and breast carcinoma dehistonized chromatins. Tissue-specific antisera against human lung and breast carcinoma dehistonized chromatins were obtained. The specificity of these antisera was determined by complement fixation. In the presence of antiserum against human lung carcinoma, only chromatins from lung carcinoma fixed complement significantly, whereas chromatins isolated from human breast carcinoma, HeLa cells, normal lung tissue, breast tissue, or term placenta were negative (i.e., inactive). In a similar assay with the use of antiserum against dehistonized breast carcinoma chromatins, only breast carcinoma chromatins fixed complement. Immunohistochemical localization of the antigens by the horseradish peroxidase bridge method demonstrated their presence in the nuclei."}
{"id": "PMID:195067", "title": "Herpesvirus saimiri-induced lymphoproliferative disease in howler monkeys.", "content": "Four of 5 howler monkeys (Alouatta caraya) experimentally infected with Herpesvirus saimiri (HVS) developed a rapidly fatal malignant lymphoma accompanied by peripheral T-cell lymphocytosis. HVS was isolated from fresh and tissue cultured blood and tissue lymphocytes and from cell cultures derived from nonlymphoid organs. Humoral antibodies against HVS-induced antigens were detected in the sera of the animals. The in vitro response of the peripheral blood lymphocytes to mitogenic stimulants was depressed following HVS infection.", "contents": "Herpesvirus saimiri-induced lymphoproliferative disease in howler monkeys. Four of 5 howler monkeys (Alouatta caraya) experimentally infected with Herpesvirus saimiri (HVS) developed a rapidly fatal malignant lymphoma accompanied by peripheral T-cell lymphocytosis. HVS was isolated from fresh and tissue cultured blood and tissue lymphocytes and from cell cultures derived from nonlymphoid organs. Humoral antibodies against HVS-induced antigens were detected in the sera of the animals. The in vitro response of the peripheral blood lymphocytes to mitogenic stimulants was depressed following HVS infection."}
{"id": "PMID:195068", "title": "Immunopathogenicity and oncogenicity of murine leukemia virus. III. Quantitation of spontaneous virus expression.", "content": "Electron microscopic determination of C-type virions in gut-associated and genital tract epithelia was made in various murine strains. The number of morphologically identifiable C-type virus particles varied more than 100-fold among strains, being high in all strains exhibiting immunologic disease, as well as several immunologically normal strains, and low in other immunologically normal strains. No relationship was seen between the number of virions found in epithelial and lymphoid tissues. There was, however, a direct correlation between numbers of virions in epithelial tissues and levels of serum gp70.", "contents": "Immunopathogenicity and oncogenicity of murine leukemia virus. III. Quantitation of spontaneous virus expression. Electron microscopic determination of C-type virions in gut-associated and genital tract epithelia was made in various murine strains. The number of morphologically identifiable C-type virus particles varied more than 100-fold among strains, being high in all strains exhibiting immunologic disease, as well as several immunologically normal strains, and low in other immunologically normal strains. No relationship was seen between the number of virions found in epithelial and lymphoid tissues. There was, however, a direct correlation between numbers of virions in epithelial tissues and levels of serum gp70."}
{"id": "PMID:195069", "title": "Effect of immune manipulation on natural immune responses to murine mammary tumor antigens.", "content": "The virus-host relationship in BALB/cfC3H virgin female mice neonatally infected with an oncogenic virus (mammary tumor virus) (MuMTV) was significantly altered by a brief immunosuppressive treatment during young adult life. Natural immune responses were augmented and changed. The ability of lymphoid cells to attack target cells expressing MuMTV-associated antigens was significantly increased, and a new component, a non-T-cell reactivity, was added to the T-cell reactivity found in normal females. Serum blocking factors were both quantitatively and qualitatively altered.", "contents": "Effect of immune manipulation on natural immune responses to murine mammary tumor antigens. The virus-host relationship in BALB/cfC3H virgin female mice neonatally infected with an oncogenic virus (mammary tumor virus) (MuMTV) was significantly altered by a brief immunosuppressive treatment during young adult life. Natural immune responses were augmented and changed. The ability of lymphoid cells to attack target cells expressing MuMTV-associated antigens was significantly increased, and a new component, a non-T-cell reactivity, was added to the T-cell reactivity found in normal females. Serum blocking factors were both quantitatively and qualitatively altered."}
{"id": "PMID:195070", "title": "Lymphoproliferative diseases of fowl: JM-V leukemic lymphoblasts in cell culture.", "content": "JM-V leukemic lymphoblasts were established in cell culture. The cultured cells (JM-VLC cells) were transplantable in young chicks and produced a disease indistinguishable from JM-V lymphoblastic leukemia as initiated by whole-blood inoculation. JM-VLC cells maintained a normal female karyotype through 13 passages in Rhode Island Red cockerels. With the use of JM-V antisera and antisera from birds with naturally occurring Marek's disease (MD), specific antigens were detected on the surfaces of living cells. Intracellular antigens were detected with anti-MD virus sera after cultivation for at least 1 day at 37 degrees C. In spite of the expression of MD antigens, the presence of herpesvirus particles associated with the cultured cells, and the occurrence of foci of multinucleated cells in kidney cultures from chicks inoculated with cellfree preparations of JM-VLC cells, the pathologic potential of the cultured cells was that of JM-V leukemia.", "contents": "Lymphoproliferative diseases of fowl: JM-V leukemic lymphoblasts in cell culture. JM-V leukemic lymphoblasts were established in cell culture. The cultured cells (JM-VLC cells) were transplantable in young chicks and produced a disease indistinguishable from JM-V lymphoblastic leukemia as initiated by whole-blood inoculation. JM-VLC cells maintained a normal female karyotype through 13 passages in Rhode Island Red cockerels. With the use of JM-V antisera and antisera from birds with naturally occurring Marek's disease (MD), specific antigens were detected on the surfaces of living cells. Intracellular antigens were detected with anti-MD virus sera after cultivation for at least 1 day at 37 degrees C. In spite of the expression of MD antigens, the presence of herpesvirus particles associated with the cultured cells, and the occurrence of foci of multinucleated cells in kidney cultures from chicks inoculated with cellfree preparations of JM-VLC cells, the pathologic potential of the cultured cells was that of JM-V leukemia."}
{"id": "PMID:195071", "title": "Isolation of T-lymphocytes from disaggregated tumors, with high purity and good percentage recovery.", "content": "A combination of two cell separation methods was utilized for the isolation of thymus-derived lymphocytes (TL) from enzymatically disaggregated tumors. Passage through Sephadex G-10-glass bead columns to remove adherent cell types followed by exposure to IgG-coated sheep red blood cell monolayers for removal of Fc receptor-bearing inflammatory cells provided functional TL suspensions of high purity with good percentage recovery.", "contents": "Isolation of T-lymphocytes from disaggregated tumors, with high purity and good percentage recovery. A combination of two cell separation methods was utilized for the isolation of thymus-derived lymphocytes (TL) from enzymatically disaggregated tumors. Passage through Sephadex G-10-glass bead columns to remove adherent cell types followed by exposure to IgG-coated sheep red blood cell monolayers for removal of Fc receptor-bearing inflammatory cells provided functional TL suspensions of high purity with good percentage recovery."}
{"id": "PMID:195072", "title": "Evidence that B-lymphocytes carry the nuclear pocket abnormality associated with bovine leukemia virus infection.", "content": "Peripheral blood lymphocytes from 3 cows with persistent lymphocytosis were separated on nylon wool columns into nylon wool-adherent and nonadherent populations. The percentage of cells coated with surface immunoglobulin (B-cells) and the frequency of lymphocytic nuclear pockets in each sub-population were then determined. In each case the adherent population consisted predominantly of B-cells with an increased nuclear pocket frequency, whereas the nonadherent cells were 98.99% negative for surface immunoglobulin (non-B-cells) and contained essentially no nuclear pockets. These findings provided additional evidence that the B-subpopulation of cells was highly involved in bovine leukemia oncogenesis.", "contents": "Evidence that B-lymphocytes carry the nuclear pocket abnormality associated with bovine leukemia virus infection. Peripheral blood lymphocytes from 3 cows with persistent lymphocytosis were separated on nylon wool columns into nylon wool-adherent and nonadherent populations. The percentage of cells coated with surface immunoglobulin (B-cells) and the frequency of lymphocytic nuclear pockets in each sub-population were then determined. In each case the adherent population consisted predominantly of B-cells with an increased nuclear pocket frequency, whereas the nonadherent cells were 98.99% negative for surface immunoglobulin (non-B-cells) and contained essentially no nuclear pockets. These findings provided additional evidence that the B-subpopulation of cells was highly involved in bovine leukemia oncogenesis."}
{"id": "PMID:195073", "title": "Partial characterization of a herpes-type virus (K9V) derived from Kaposi's sarcoma.", "content": "A herpes-type virus that was originally isolated from a cell culture (designated K9V) derived from a tumor biopsy specimen from a patient with Kaposi's sarcoma was partially characterized. The host range of K9V, as determined by the induction of virus-specific cytopathology, synthesis of antigens, and plaque formation, was limited to human cells and particularly to fibroblasts. Immunofluorescence and complement fixation assays confirmed the specificity of the presence of cytomegalovirus (CMV)-type antigens in K9V-infected human fibroblasts. In addition, the density of K9V DNA was consistent with the density of CMV DNA. However, some peculiarities were observed in the K9V strain of CMV. The virus seemed more cell-associated in human fibroblasts than were known laboratory strains: The spread of cytopathology was slow and did not always involve the whole cell sheet, and the total regression of cytopathology with the establishment of a persistent infection was common. Similar characteristics have recently been observed in the Mj strain of CMV, which has been shown to be oncogenic in human fibroblasts.", "contents": "Partial characterization of a herpes-type virus (K9V) derived from Kaposi's sarcoma. A herpes-type virus that was originally isolated from a cell culture (designated K9V) derived from a tumor biopsy specimen from a patient with Kaposi's sarcoma was partially characterized. The host range of K9V, as determined by the induction of virus-specific cytopathology, synthesis of antigens, and plaque formation, was limited to human cells and particularly to fibroblasts. Immunofluorescence and complement fixation assays confirmed the specificity of the presence of cytomegalovirus (CMV)-type antigens in K9V-infected human fibroblasts. In addition, the density of K9V DNA was consistent with the density of CMV DNA. However, some peculiarities were observed in the K9V strain of CMV. The virus seemed more cell-associated in human fibroblasts than were known laboratory strains: The spread of cytopathology was slow and did not always involve the whole cell sheet, and the total regression of cytopathology with the establishment of a persistent infection was common. Similar characteristics have recently been observed in the Mj strain of CMV, which has been shown to be oncogenic in human fibroblasts."}
{"id": "PMID:195074", "title": "Antibodies to Epstein-Barr virus in nasopharyngeal carcinoma and other neoplastic conditions.", "content": "Sera from patients with nasopharyngeal carcinoma (NPC) or other malignant diseases and from apparently healthy controls were examined for Epstein-Barr virus (EBV) antibodies. A difference existed in the percentage of positive sera among the groups studied. High-titer antibody levels were observed in the NPC group, but no statistical difference was found among other groups of patients and controls. The data reaffirmed the association of EBV with NPC but did not support its etiologic role in the development of other human neoplasms.", "contents": "Antibodies to Epstein-Barr virus in nasopharyngeal carcinoma and other neoplastic conditions. Sera from patients with nasopharyngeal carcinoma (NPC) or other malignant diseases and from apparently healthy controls were examined for Epstein-Barr virus (EBV) antibodies. A difference existed in the percentage of positive sera among the groups studied. High-titer antibody levels were observed in the NPC group, but no statistical difference was found among other groups of patients and controls. The data reaffirmed the association of EBV with NPC but did not support its etiologic role in the development of other human neoplasms."}
{"id": "PMID:195075", "title": "Establishment of an Epstein-Barr virus-determined nuclear antigen-negative human B-cell line from acute lymphoblastic leukemia.", "content": "A human B-cell line designated as BALL-1 was established from the peripheral blood of a patient with acute lymphoblastic leukemia (ALL). Neither Epstein-Barr virus (EBV) particles nor EBV-determined nuclear antigen (EBNA) was detectable. The morphologic and growth characteristics were clearly distinct from those of numerous EBV-positive lymphoblastoid cell lines previously reported. BALL-1 cells probably originated from the donor's leukemia cells as judged from their cytogenetic, morphologic, and surface features. The BALL-1 line was the first EBNA-negative B-cell line established from ALL.", "contents": "Establishment of an Epstein-Barr virus-determined nuclear antigen-negative human B-cell line from acute lymphoblastic leukemia. A human B-cell line designated as BALL-1 was established from the peripheral blood of a patient with acute lymphoblastic leukemia (ALL). Neither Epstein-Barr virus (EBV) particles nor EBV-determined nuclear antigen (EBNA) was detectable. The morphologic and growth characteristics were clearly distinct from those of numerous EBV-positive lymphoblastoid cell lines previously reported. BALL-1 cells probably originated from the donor's leukemia cells as judged from their cytogenetic, morphologic, and surface features. The BALL-1 line was the first EBNA-negative B-cell line established from ALL."}
{"id": "PMID:195076", "title": "Plasma ACTH in rats following medical adrenalectomy.", "content": "We have previously reported that surgically adrenalectomized nonstressed rats showed delayed secretion of the expected increase in plasma ACTH concentrations following adrenalectomy.(1) However, increased plasma ACTH concentrations were always detected when these animals were subjected to severe stress, and their responsiveness increased again seven days or more following surgical adrenalectomy. We are now reporting similar results which were obtained following prolonged systemic glucocorticoid administration (medical adrenalectomy) in similar groups of rats.", "contents": "Plasma ACTH in rats following medical adrenalectomy. We have previously reported that surgically adrenalectomized nonstressed rats showed delayed secretion of the expected increase in plasma ACTH concentrations following adrenalectomy.(1) However, increased plasma ACTH concentrations were always detected when these animals were subjected to severe stress, and their responsiveness increased again seven days or more following surgical adrenalectomy. We are now reporting similar results which were obtained following prolonged systemic glucocorticoid administration (medical adrenalectomy) in similar groups of rats."}
{"id": "PMID:195079", "title": "Alteration of the intracellular energetic and ionic conditions by mengovirus infection of Ehrlich ascites tumor cells and its influence on protein synthesis in the midphase of infection.", "content": "Mengovirus infection of Ehrlich ascites tumor cells caused a change of the intracellular ATP concentration. It increased by 35% within the first 3 h postinfection and then declined to zero within the next 5 h. The decrease in the ATP concentration was due, at least in part, to leakage of ATP into the medium, where it could be demonstrated by the luciferin-luciferase assay. Gross leakage of ATP was observed at 4.5 h postinfection, concomitant with the production of the first intracellular, infectious virus particles. A similar concentration decrease was detected for Mg(2+), the polyamines, and K(+), whereas an increase in the Na(+) concentration was observed. The intracellular Mg(2+) concentration varied synchronously with the ATP level, rising by 16% during the first 3 h postinfection and then progressively falling to lower values in the late period of the infectious cycle. After an initial slight enhancement, the putrescine, spermidine, and spermine concentrations declined at about 1.5 h postinfection. Wherease the intracellular K(+) concentration increased by 17% during the first hour postinfection, the Na(+) concentration diminished by the same value within the same time period, leaving the internal ionic strength unchanged early in infection. Three hours after the beginning of virus infection, there was a rapid decline of K(+) and enhancement of Na(+) within the cell. These alterations of the intracellular energetic and ionic conditions seem to be, at least in part, responsible for the cessation of virus-specific protein synthesis in mengovirus-infected Ehrlich ascites tumor cells commencing 3 to 3.5 h postinfection.", "contents": "Alteration of the intracellular energetic and ionic conditions by mengovirus infection of Ehrlich ascites tumor cells and its influence on protein synthesis in the midphase of infection. Mengovirus infection of Ehrlich ascites tumor cells caused a change of the intracellular ATP concentration. It increased by 35% within the first 3 h postinfection and then declined to zero within the next 5 h. The decrease in the ATP concentration was due, at least in part, to leakage of ATP into the medium, where it could be demonstrated by the luciferin-luciferase assay. Gross leakage of ATP was observed at 4.5 h postinfection, concomitant with the production of the first intracellular, infectious virus particles. A similar concentration decrease was detected for Mg(2+), the polyamines, and K(+), whereas an increase in the Na(+) concentration was observed. The intracellular Mg(2+) concentration varied synchronously with the ATP level, rising by 16% during the first 3 h postinfection and then progressively falling to lower values in the late period of the infectious cycle. After an initial slight enhancement, the putrescine, spermidine, and spermine concentrations declined at about 1.5 h postinfection. Wherease the intracellular K(+) concentration increased by 17% during the first hour postinfection, the Na(+) concentration diminished by the same value within the same time period, leaving the internal ionic strength unchanged early in infection. Three hours after the beginning of virus infection, there was a rapid decline of K(+) and enhancement of Na(+) within the cell. These alterations of the intracellular energetic and ionic conditions seem to be, at least in part, responsible for the cessation of virus-specific protein synthesis in mengovirus-infected Ehrlich ascites tumor cells commencing 3 to 3.5 h postinfection."}
{"id": "PMID:195080", "title": "Analysis of precursors to the envelope glycoproteins of avian RNA tumor viruses in chicken and quail cells.", "content": "Immune precipitation with monospecific antiserum was employed to study the intracellular synthesis of viral glycoproteins gp85 and gp37. Labeled gp85 and gp37 were detected from lysates of cells transformed with Rous sacroma virus, strain B77, after long-term labeling with radioactive glucosamine or phenylalanine. Immune precipitates prepared from lysates of cells pulse-labeled for a short time resulted in a glycoprotein of 92,000 molecular weight (gp92). This precursor was stable in B77-transformed Japanese quail cells for several hours, whereas in chicken cells it could be chased within a few hours into virion glycoproteins gp85 and gp37. Similarly, the precursor for the structural viral proteins, pr76, persisted in quail cells much longer than in chicken cells. During very short pulses or in the presence of a glucosamine block (25 mM glucosamine), the antiserum against the viral envelope glycoproteins detected a precursor of higher electrophoretic mobility of approximately 70,000 molecular weight, \"p70.\" Fucose label entered gp92 and gp85 as well as \"p70.\" Proteolytic treatment of virion-bound gp85 in vitro generated two discrete glycoproteins of 62,000 and 45,000 molecular weight, but did not result in an increase in the amount of gp37.", "contents": "Analysis of precursors to the envelope glycoproteins of avian RNA tumor viruses in chicken and quail cells. Immune precipitation with monospecific antiserum was employed to study the intracellular synthesis of viral glycoproteins gp85 and gp37. Labeled gp85 and gp37 were detected from lysates of cells transformed with Rous sacroma virus, strain B77, after long-term labeling with radioactive glucosamine or phenylalanine. Immune precipitates prepared from lysates of cells pulse-labeled for a short time resulted in a glycoprotein of 92,000 molecular weight (gp92). This precursor was stable in B77-transformed Japanese quail cells for several hours, whereas in chicken cells it could be chased within a few hours into virion glycoproteins gp85 and gp37. Similarly, the precursor for the structural viral proteins, pr76, persisted in quail cells much longer than in chicken cells. During very short pulses or in the presence of a glucosamine block (25 mM glucosamine), the antiserum against the viral envelope glycoproteins detected a precursor of higher electrophoretic mobility of approximately 70,000 molecular weight, \"p70.\" Fucose label entered gp92 and gp85 as well as \"p70.\" Proteolytic treatment of virion-bound gp85 in vitro generated two discrete glycoproteins of 62,000 and 45,000 molecular weight, but did not result in an increase in the amount of gp37."}
{"id": "PMID:195081", "title": "Donation of N- or B-tropic phenotype to NB-tropic murine leukemia virus during mixed infections.", "content": "The IC isolate of Moloney murine leukemia virus (MuLV), which is NB-tropic, was grown in cells producing conditionally defective or defective virus particles derived from N- or B-tropic MuLV. The infectious MuLV that was then released was found to be sensitive to Fv-1 restriction but produced NB-tropic progeny upon passage. These results indicate that this NB-tropic MuLV can acquire sensitivity to Fv-1 restriction by phenotypic mixing with N- or B-tropic MuLV. It is thus suggested that NB-tropic MuLV is insensitive to Fv-1 restriction simply because it lacks the determinants of tropism.", "contents": "Donation of N- or B-tropic phenotype to NB-tropic murine leukemia virus during mixed infections. The IC isolate of Moloney murine leukemia virus (MuLV), which is NB-tropic, was grown in cells producing conditionally defective or defective virus particles derived from N- or B-tropic MuLV. The infectious MuLV that was then released was found to be sensitive to Fv-1 restriction but produced NB-tropic progeny upon passage. These results indicate that this NB-tropic MuLV can acquire sensitivity to Fv-1 restriction by phenotypic mixing with N- or B-tropic MuLV. It is thus suggested that NB-tropic MuLV is insensitive to Fv-1 restriction simply because it lacks the determinants of tropism."}
{"id": "PMID:195082", "title": "Formation of reticuloendotheliosis virus pseudotypes of Rous sarcoma virus.", "content": "Superinfection of chicken embryo fibroblasts transformed by the defective Bryan strain of Rous sarcoma virus (BH-RSV) with two different reticuloendotheliosis viruses (REVs), REV strain T (REV-T) or spleen necrosis virus (SNV), resulted in the production of infectious sarcoma virus pseudotypes. These pseudotypes were neutralized by antiserum prepared against SNV and were unable to infect chicken cells preinfected with either REV-T or SNV. These results suggest that defective BH-RSV is able to use the glycoprotein from REV to form infectious pseudotypes. On the other hand, neither REV-T nor SNV was able to supply a functional reverse transcriptase to the polymerase-negative mutant BH-RSValpha, nor was REV-T or SNV able to complement the defect in the internal protein gene of the temperature-sensitive avian sarcoma virus mutant NY45.", "contents": "Formation of reticuloendotheliosis virus pseudotypes of Rous sarcoma virus. Superinfection of chicken embryo fibroblasts transformed by the defective Bryan strain of Rous sarcoma virus (BH-RSV) with two different reticuloendotheliosis viruses (REVs), REV strain T (REV-T) or spleen necrosis virus (SNV), resulted in the production of infectious sarcoma virus pseudotypes. These pseudotypes were neutralized by antiserum prepared against SNV and were unable to infect chicken cells preinfected with either REV-T or SNV. These results suggest that defective BH-RSV is able to use the glycoprotein from REV to form infectious pseudotypes. On the other hand, neither REV-T nor SNV was able to supply a functional reverse transcriptase to the polymerase-negative mutant BH-RSValpha, nor was REV-T or SNV able to complement the defect in the internal protein gene of the temperature-sensitive avian sarcoma virus mutant NY45."}
{"id": "PMID:195083", "title": "Multiple free viral DNA copies in polyoma virus-transformed mouse cells surviving productive infection.", "content": "Mouse 3T6 cells were infected with polyoma virus at high multiplicity, and survivors were isolated. Clones from single cells were then established and were found to be resistant to a second infection. However, in some clones viral functions could at least be partially expressed during reinfection, as judged from a stimulation of nuclear tumor antigen expression. One such clone was studied in detail. These cells were transformed and produced low amounts of virus (less than 1 PFU per cell per generation). The persistent infection did not seem to be a carrier-state phenomenon, since infectious-center assays showed that most cells produced virus. The resistance of the cells to reinfection can be explained by interference from viral DNA present in the cells, averaging about 1,500 \"free\" copies per cell. This DNA had the normal physical characteristics of polyoma DNA. However, it had a slightly larger size than authentic polyoma DNA. Mapping with restriction endonucleases showed that the addition to the DNA was about 5% of the wild-type genome and was located close to the origin of DNA replication. This DNA was infectious, although it had a 10-fold lower infectivity than wild-type polyoma DNA. Both virus and DNA from the polyoma-resistant cells had a small-plaque morphology, as opposed to the large-plaque morphology of the virus used for the initial selection of cells.", "contents": "Multiple free viral DNA copies in polyoma virus-transformed mouse cells surviving productive infection. Mouse 3T6 cells were infected with polyoma virus at high multiplicity, and survivors were isolated. Clones from single cells were then established and were found to be resistant to a second infection. However, in some clones viral functions could at least be partially expressed during reinfection, as judged from a stimulation of nuclear tumor antigen expression. One such clone was studied in detail. These cells were transformed and produced low amounts of virus (less than 1 PFU per cell per generation). The persistent infection did not seem to be a carrier-state phenomenon, since infectious-center assays showed that most cells produced virus. The resistance of the cells to reinfection can be explained by interference from viral DNA present in the cells, averaging about 1,500 \"free\" copies per cell. This DNA had the normal physical characteristics of polyoma DNA. However, it had a slightly larger size than authentic polyoma DNA. Mapping with restriction endonucleases showed that the addition to the DNA was about 5% of the wild-type genome and was located close to the origin of DNA replication. This DNA was infectious, although it had a 10-fold lower infectivity than wild-type polyoma DNA. Both virus and DNA from the polyoma-resistant cells had a small-plaque morphology, as opposed to the large-plaque morphology of the virus used for the initial selection of cells."}
{"id": "PMID:195084", "title": "Simian virus 40 gene A regulates the association between a highly phosphorylated protein and chromatin and ribosomes in simian virus 40-transformed cells.", "content": "The species of proteins associated with chromatin and ribosomes of simian virus 40 (SV40)-transformed and untransformed monkey, mouse, and rat cells have been compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after phosphorylation of these proteins either in vivo or in vitro. In vitro phosphorylation was carried out by protein kinase associated with these organelles and [gamma-(32) P]ATP as the phosphoryl donor. The reaction products contained both phosphoserine and phosphothreonine in approximately equal amounts. The electrophoretic analysis of the phosphorylated proteins revealed that the highly phosphorylated protein with a molecular weight of approximately 90,000 (90K protein) was associated with chromatin and ribosomes from transformed cells but not from untransformed cells. The 90K protein could be extracted from chromatin and ribosomes with 0.5 to 1.0 M NaCl or KCl. The 90K protein was still associated with the runoff ribosomes prepared by the puromycin reaction of the post-mitochondrial supernatant in the protein-synthesizing system. In vitro phosphorylation of chromatin and ribosomes from SV40 tsA-transformed mouse and rat cells indicated that the amounts of 90K protein associated with these organelles decreased greatly when the cells were cultivated at the restrictive temperature. A similar temperature-dependent decrease in the amount of (32)P-labeled 90K protein was observed in nonhistone chromosomal and ribosome-associated protein fractions prepared from SV40 tsA-transformed cells labeled with [(3)H]leucine and [(32)P]orthophosphate in vivo. In vitro phosphorylated 90K protein in nonhistone chromosomal and ribosome-associated proteins extracted with high salt was not immunoprecipitated with anti-SV40 T sera.", "contents": "Simian virus 40 gene A regulates the association between a highly phosphorylated protein and chromatin and ribosomes in simian virus 40-transformed cells. The species of proteins associated with chromatin and ribosomes of simian virus 40 (SV40)-transformed and untransformed monkey, mouse, and rat cells have been compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after phosphorylation of these proteins either in vivo or in vitro. In vitro phosphorylation was carried out by protein kinase associated with these organelles and [gamma-(32) P]ATP as the phosphoryl donor. The reaction products contained both phosphoserine and phosphothreonine in approximately equal amounts. The electrophoretic analysis of the phosphorylated proteins revealed that the highly phosphorylated protein with a molecular weight of approximately 90,000 (90K protein) was associated with chromatin and ribosomes from transformed cells but not from untransformed cells. The 90K protein could be extracted from chromatin and ribosomes with 0.5 to 1.0 M NaCl or KCl. The 90K protein was still associated with the runoff ribosomes prepared by the puromycin reaction of the post-mitochondrial supernatant in the protein-synthesizing system. In vitro phosphorylation of chromatin and ribosomes from SV40 tsA-transformed mouse and rat cells indicated that the amounts of 90K protein associated with these organelles decreased greatly when the cells were cultivated at the restrictive temperature. A similar temperature-dependent decrease in the amount of (32)P-labeled 90K protein was observed in nonhistone chromosomal and ribosome-associated protein fractions prepared from SV40 tsA-transformed cells labeled with [(3)H]leucine and [(32)P]orthophosphate in vivo. In vitro phosphorylated 90K protein in nonhistone chromosomal and ribosome-associated proteins extracted with high salt was not immunoprecipitated with anti-SV40 T sera."}
{"id": "PMID:195085", "title": "Characterization of simian virus 40 tsA58 transcriptional intermediates at restrictive temperatures: relationship between DNA replication and transcription.", "content": "When nuclei from simian virus 40 (SV40)-infected cells are lysed with Sarkosyl and the chromatin is pelleted, the supernatant fluid contains a nucleoprotein complex capable of synthesizing viral RNA (Laub and Aloni, Virology 75:346-354, 1976; Gariglio and Mousset, FEBS Lett. 56:149-155, 1975). The level of activity of the RNA polymerase in the complex increased during infection in parallel with the amount of viral DNA that had been synthesized. If cells infected at 33 degrees C with the SV40 mutant tsA 58 were shifted to the nonpermissive temperature of 40 degrees C at any time between 18 and 48 h postinfection, no viral DNA replication was detected after 45 min and no new rounds of synthesis were initiated after 20 to 30 min. However, after this shift, polymerase activity associated with the nucleo-protein complex did continue to increase for 5 h, at which time it reached a plateau. There was an increase of RNA synthesized from both the early (E) and late (L) SV40 DNA strands, and there was a threefold increase in the ratio of early-to-late RNA species after the shift. In comparable experiments with cells infected with wild-type virions, no increase in polymerase activity occurred because of the temperature change alone. At 33 degrees C, the relative amount of RNA transcribed from the wild-type E-strand was less than tsA 58 at 33 degrees C and did not increase after a shift to 40 degrees C. The tsA 58 transcriptional complexes extracted from cells grown at 33 degrees C sedimented heterogeneously in sucrose gradients, with a peak near 26S. There were no detectable alterations in the sedimentation properties of the complexes when tsA 58-infected cells were shifted to 40 degrees C for 2 h. We conclude that continued synthesis of viral DNA is not an obligatory prerequisite for maintenance of late viral transcription nor is the sedimentation of the transcriptional complex at 26S related to actively replicating DNA molecules serving as templates for transcription. Further, an increase in late transcription can occur under conditions where reinitiation of viral DNA synthesis is prevented. The increase in the synthesis of early and late RNA at the restrictive temperature without concurrent DNA synthesis is discussed in relationship to the function of the A gene product.", "contents": "Characterization of simian virus 40 tsA58 transcriptional intermediates at restrictive temperatures: relationship between DNA replication and transcription. When nuclei from simian virus 40 (SV40)-infected cells are lysed with Sarkosyl and the chromatin is pelleted, the supernatant fluid contains a nucleoprotein complex capable of synthesizing viral RNA (Laub and Aloni, Virology 75:346-354, 1976; Gariglio and Mousset, FEBS Lett. 56:149-155, 1975). The level of activity of the RNA polymerase in the complex increased during infection in parallel with the amount of viral DNA that had been synthesized. If cells infected at 33 degrees C with the SV40 mutant tsA 58 were shifted to the nonpermissive temperature of 40 degrees C at any time between 18 and 48 h postinfection, no viral DNA replication was detected after 45 min and no new rounds of synthesis were initiated after 20 to 30 min. However, after this shift, polymerase activity associated with the nucleo-protein complex did continue to increase for 5 h, at which time it reached a plateau. There was an increase of RNA synthesized from both the early (E) and late (L) SV40 DNA strands, and there was a threefold increase in the ratio of early-to-late RNA species after the shift. In comparable experiments with cells infected with wild-type virions, no increase in polymerase activity occurred because of the temperature change alone. At 33 degrees C, the relative amount of RNA transcribed from the wild-type E-strand was less than tsA 58 at 33 degrees C and did not increase after a shift to 40 degrees C. The tsA 58 transcriptional complexes extracted from cells grown at 33 degrees C sedimented heterogeneously in sucrose gradients, with a peak near 26S. There were no detectable alterations in the sedimentation properties of the complexes when tsA 58-infected cells were shifted to 40 degrees C for 2 h. We conclude that continued synthesis of viral DNA is not an obligatory prerequisite for maintenance of late viral transcription nor is the sedimentation of the transcriptional complex at 26S related to actively replicating DNA molecules serving as templates for transcription. Further, an increase in late transcription can occur under conditions where reinitiation of viral DNA synthesis is prevented. The increase in the synthesis of early and late RNA at the restrictive temperature without concurrent DNA synthesis is discussed in relationship to the function of the A gene product."}
{"id": "PMID:195086", "title": "In vitro translation of Harvey murine sarcoma virus RNA.", "content": "The viral RNA of the Harvey strain of murine sarcoma virus (Ha-SV), which does not encode for any known viral structural polypeptides, has been translated in a nuclease-digested, cell-free system. The major protein product of the in vitro translation reaction has a molecular weight of 21,000 and is initiated faithfully with [35S]formylmethionine from formyl-[35S]methionyl-tRNAFMET. This polypeptide is clearly distinct from the RNA of the Moloney strain of type C helper virus used to pseudotype the Ha-SV. The intensity of the 21,000-dalton polypeptide on gels correlates well to the concentration of Ha-SV RNA in different viral RNA preparations. These experiments indicate that a polypeptide marker for Ha-SV is now available for the first time. The possibility that this protein is the product of the rat portion of the Ha-SV genome is discussed.", "contents": "In vitro translation of Harvey murine sarcoma virus RNA. The viral RNA of the Harvey strain of murine sarcoma virus (Ha-SV), which does not encode for any known viral structural polypeptides, has been translated in a nuclease-digested, cell-free system. The major protein product of the in vitro translation reaction has a molecular weight of 21,000 and is initiated faithfully with [35S]formylmethionine from formyl-[35S]methionyl-tRNAFMET. This polypeptide is clearly distinct from the RNA of the Moloney strain of type C helper virus used to pseudotype the Ha-SV. The intensity of the 21,000-dalton polypeptide on gels correlates well to the concentration of Ha-SV RNA in different viral RNA preparations. These experiments indicate that a polypeptide marker for Ha-SV is now available for the first time. The possibility that this protein is the product of the rat portion of the Ha-SV genome is discussed."}
{"id": "PMID:195087", "title": "Regulation of herpesvirus macromolecular synthesis. VI. Synthesis and modification of viral polypeptides in enucleated cells.", "content": "Cells were enucleated with cytochalasin B after infection with herpes simplex virus 1. When protein synthesis was blocked by cycloheximide from the time of infection, mRNA for viral alpha-infected cell polypeptides (ICP) 4, 0, and 27 accumulated in the cytoplasm and was expressed after the removal of both drug and nucleus. A host protein, ICP 22, whose synthesis is stimulated in intact cells, was not made, and viral protein ICP4, which is normally modified to a form that migrates more slowly in polyacrylamide gels, was not modified in the absence of the nucleus. After enucleation at 2 h postinfection, a number of viral beta and gamma proteins continued to be made, starting at 20 to 25% of the normal rates and declining with a half-time of about 2 h. The synthesis of ICP 4 declined more rapidly, suggesting that it is switched off in the cytoplasm.", "contents": "Regulation of herpesvirus macromolecular synthesis. VI. Synthesis and modification of viral polypeptides in enucleated cells. Cells were enucleated with cytochalasin B after infection with herpes simplex virus 1. When protein synthesis was blocked by cycloheximide from the time of infection, mRNA for viral alpha-infected cell polypeptides (ICP) 4, 0, and 27 accumulated in the cytoplasm and was expressed after the removal of both drug and nucleus. A host protein, ICP 22, whose synthesis is stimulated in intact cells, was not made, and viral protein ICP4, which is normally modified to a form that migrates more slowly in polyacrylamide gels, was not modified in the absence of the nucleus. After enucleation at 2 h postinfection, a number of viral beta and gamma proteins continued to be made, starting at 20 to 25% of the normal rates and declining with a half-time of about 2 h. The synthesis of ICP 4 declined more rapidly, suggesting that it is switched off in the cytoplasm."}
{"id": "PMID:195088", "title": "Replication of herpesvirus DNA. III. Rate of DNA elongation.", "content": "The rate of pseudorabies virus DNA elongation was measured by three different techniques: density shift experiments, radioautography examined by light microscopy, and radioautography examined by electron microscopy. The rate of the fork movement at 37 degrees C was estimated to be approximately 1 micron/min.", "contents": "Replication of herpesvirus DNA. III. Rate of DNA elongation. The rate of pseudorabies virus DNA elongation was measured by three different techniques: density shift experiments, radioautography examined by light microscopy, and radioautography examined by electron microscopy. The rate of the fork movement at 37 degrees C was estimated to be approximately 1 micron/min."}
{"id": "PMID:195089", "title": "Cell-free synthesis of herpes simplex virus proteins.", "content": "Polyribosomes isolated from herpes simplex virus type I (HSV-1)-infected cells have been used to program a eucaryotic cell-free translation system. At least 10 HSV-specific polypeptides, with apparent molecular weights of 25,000 to 160,000, are synthesized by wild-type HSV-infected polyribosomes. Polyribosomes prepared from thymidine kinase-negative mutants of HSV direct the synthesis of three putative nonsense termination polypeptides. HSV-specific polypeptides synthesized in vitro are precipitated with antiserum to HSV-infected cell proteins.", "contents": "Cell-free synthesis of herpes simplex virus proteins. Polyribosomes isolated from herpes simplex virus type I (HSV-1)-infected cells have been used to program a eucaryotic cell-free translation system. At least 10 HSV-specific polypeptides, with apparent molecular weights of 25,000 to 160,000, are synthesized by wild-type HSV-infected polyribosomes. Polyribosomes prepared from thymidine kinase-negative mutants of HSV direct the synthesis of three putative nonsense termination polypeptides. HSV-specific polypeptides synthesized in vitro are precipitated with antiserum to HSV-infected cell proteins."}
{"id": "PMID:195090", "title": "Episomal viral DNA in a Herpesvirus saimiri-transformed lymphoid cell line.", "content": "The lymphoid cell line #1670 has been derived from the infiltrated spleen of a tumor-bearing marmoset monkey infected with Herpesvirus saimiri. The cells contain both types of H. saimiri DNA, unique light (L-) DNA (36% cytosine plus guanine) and repetitive heavy (H-) DNA (71% cytosine plus guanine), without producing infectious virus. Viral DNA was found to persist in these cells as nonintegrated circular DNA molecules. Closed circular superhelical viral DNA molecules were isolated by three subsequent centrifugation steps: (i) isopycnic centrifugation in CsCl, (ii) sedimentation through glycerol gradients, and (iii) equilibrium centrifugation in CsCl-ethidium bromide. The isolated circles had a molecular weight of 131.5 +/- 3.6 x 10(6). This is significantly higher than the molecular weight of linear DNA molecules isolated from purified H. saimiri virions (about 100 x 10(6)). Partial denaturation mapping of circular molecules from #1670 lymphoid cells showed uniform arrangement of H- and L-DNA sequences in all circles. All denatured molecules contained two L-DNA regions (molecular weights of 54.0 +/- 1.8 x 10(6) and 31.5 +/- 1.3 x 10(6)) and two H-DNA regions (molecular weight of 25.6 +/- 1.9 x 10(6) and 20.0 +/- 0.8 x 10(6)) of constant length. Maps of both L-regions suggested that the sequences of the shorter L-DNA region were a subset of those of the longer region. The sequences of both L-regions had the same orientation. Circular molecules from H. saimiri-transformed lymphoid cell line #1670 appeared to represent defective genomes, containing only 75% of the genetic information present in L-DNA of H. saimiri virions.", "contents": "Episomal viral DNA in a Herpesvirus saimiri-transformed lymphoid cell line. The lymphoid cell line #1670 has been derived from the infiltrated spleen of a tumor-bearing marmoset monkey infected with Herpesvirus saimiri. The cells contain both types of H. saimiri DNA, unique light (L-) DNA (36% cytosine plus guanine) and repetitive heavy (H-) DNA (71% cytosine plus guanine), without producing infectious virus. Viral DNA was found to persist in these cells as nonintegrated circular DNA molecules. Closed circular superhelical viral DNA molecules were isolated by three subsequent centrifugation steps: (i) isopycnic centrifugation in CsCl, (ii) sedimentation through glycerol gradients, and (iii) equilibrium centrifugation in CsCl-ethidium bromide. The isolated circles had a molecular weight of 131.5 +/- 3.6 x 10(6). This is significantly higher than the molecular weight of linear DNA molecules isolated from purified H. saimiri virions (about 100 x 10(6)). Partial denaturation mapping of circular molecules from #1670 lymphoid cells showed uniform arrangement of H- and L-DNA sequences in all circles. All denatured molecules contained two L-DNA regions (molecular weights of 54.0 +/- 1.8 x 10(6) and 31.5 +/- 1.3 x 10(6)) and two H-DNA regions (molecular weight of 25.6 +/- 1.9 x 10(6) and 20.0 +/- 0.8 x 10(6)) of constant length. Maps of both L-regions suggested that the sequences of the shorter L-DNA region were a subset of those of the longer region. The sequences of both L-regions had the same orientation. Circular molecules from H. saimiri-transformed lymphoid cell line #1670 appeared to represent defective genomes, containing only 75% of the genetic information present in L-DNA of H. saimiri virions."}
{"id": "PMID:195091", "title": "Presence of Epstein-Barr virus receptors, but absence of virus penetration, in cells of an Epstein-Barr virus genome-negative human lymphoblastoid T line (Molt 4).", "content": "This paper reports a unique type of interaction of Epstein-Barr virus (EBV) with an EBV receptor-positive, genome-negative human lymphoid T cell line (Molt 4), which can be summarized as follows. Although Molt 4 cells express receptors for EBV, they appear to block the penetration of this virus. These observations are derived from combined studies with immunofluorescence and electron microscopy. It is possible that T cell lines bearing receptors for EBV may express such a control on virus penetration.", "contents": "Presence of Epstein-Barr virus receptors, but absence of virus penetration, in cells of an Epstein-Barr virus genome-negative human lymphoblastoid T line (Molt 4). This paper reports a unique type of interaction of Epstein-Barr virus (EBV) with an EBV receptor-positive, genome-negative human lymphoid T cell line (Molt 4), which can be summarized as follows. Although Molt 4 cells express receptors for EBV, they appear to block the penetration of this virus. These observations are derived from combined studies with immunofluorescence and electron microscopy. It is possible that T cell lines bearing receptors for EBV may express such a control on virus penetration."}
{"id": "PMID:195092", "title": "Electrophoretic analysis of the molecular weight of murine mammary tumor virus RNA.", "content": "Molecular weight determinations of native and subunit RNAs of murine mammary tumor virus (MuMTV), a type B oncornavirus, were performed by polyacrylamide gel electrophoresis and compared with molecular weights of well-characterized avian cellular RNAs and tobacco mosaic virus RNA. From extrapolations of semilog plots of the molecular weights of the standard RNAs versus relative electrophoretic mobilities and Ferguson plots, the subunit and native RNAs of MuMTV were found to possess molecular weights of 2.93 X 10(6) and 6.45 X 10(6), respectively. These data support the assumption that two subunit molecules comprise the native RNA of MuMTV.", "contents": "Electrophoretic analysis of the molecular weight of murine mammary tumor virus RNA. Molecular weight determinations of native and subunit RNAs of murine mammary tumor virus (MuMTV), a type B oncornavirus, were performed by polyacrylamide gel electrophoresis and compared with molecular weights of well-characterized avian cellular RNAs and tobacco mosaic virus RNA. From extrapolations of semilog plots of the molecular weights of the standard RNAs versus relative electrophoretic mobilities and Ferguson plots, the subunit and native RNAs of MuMTV were found to possess molecular weights of 2.93 X 10(6) and 6.45 X 10(6), respectively. These data support the assumption that two subunit molecules comprise the native RNA of MuMTV."}
{"id": "PMID:195093", "title": "Properties of the polyoma viruses induced from BHK-21 cells transformed by A gene mutants.", "content": "Polyoma viruses induced to replicate at 31 degrees C in BHK-21 cells transformed by polyoma A gene mutants retain the thermosensitive growth characteristics and genome structure of the original mutants used for transformation.", "contents": "Properties of the polyoma viruses induced from BHK-21 cells transformed by A gene mutants. Polyoma viruses induced to replicate at 31 degrees C in BHK-21 cells transformed by polyoma A gene mutants retain the thermosensitive growth characteristics and genome structure of the original mutants used for transformation."}
{"id": "PMID:195094", "title": "Characterization of visna virus envelope neuraminic acid.", "content": "Visna virus particles inhibit influenza virus hemagglutination in an assay for neuraminic acid-containing viruses. Pretreatment of visna virus with neuraminidase abolished hemagglutination inhibition activity but did not significantly affect attachment, infectivity, or virus-induced cell fusion in sheep choroid plexus cell monolayers.", "contents": "Characterization of visna virus envelope neuraminic acid. Visna virus particles inhibit influenza virus hemagglutination in an assay for neuraminic acid-containing viruses. Pretreatment of visna virus with neuraminidase abolished hemagglutination inhibition activity but did not significantly affect attachment, infectivity, or virus-induced cell fusion in sheep choroid plexus cell monolayers."}
{"id": "PMID:195095", "title": "Mucinous adenocarcinoma of the prostate.", "content": "The third case of mucous-forming adenocarcinoma of the prostate with metastases to the bone is reported. The primary tumor was unresponsive to definitive radiotherapy and subsequent metastases to the lung, liver and bone failed to respond to hormonal manipulation and chemotherapy.", "contents": "Mucinous adenocarcinoma of the prostate. The third case of mucous-forming adenocarcinoma of the prostate with metastases to the bone is reported. The primary tumor was unresponsive to definitive radiotherapy and subsequent metastases to the lung, liver and bone failed to respond to hormonal manipulation and chemotherapy."}
{"id": "PMID:195096", "title": "Androgen binding in human testis.", "content": "Cytosol preparations of human testis contain macromolecules that bind tritiated dihydrotestosterone. Studies of steroid competition, heat sensitivity and dissociation rate constants indicate a similarity to serum testosterone-estradiol-binding globulin. The amount of binding of tritiated dihydrotestosterone is greater than could be explained by contamination of testis by serum.", "contents": "Androgen binding in human testis. Cytosol preparations of human testis contain macromolecules that bind tritiated dihydrotestosterone. Studies of steroid competition, heat sensitivity and dissociation rate constants indicate a similarity to serum testosterone-estradiol-binding globulin. The amount of binding of tritiated dihydrotestosterone is greater than could be explained by contamination of testis by serum."}
{"id": "PMID:195097", "title": "Pancreatic carcinoma. Survival following detection by ultrasonic scanning.", "content": "The survival of 28 patients with pancreatic cancer was studied following initial detection of this malignant neoplasm by ultrasonic scanning. By ultrasound examination, 24 patients had an abnormality, and 21 had a demonstrable mass. Twenty-seven patients are now deceased, and the overall survival ranged from eight days to 24 months (mean, 6.1 months). The results of this study indicate that diagnosis by ultrasonic scanning had no effect on the survival of patients with pancreatic carcinoma.", "contents": "Pancreatic carcinoma. Survival following detection by ultrasonic scanning. The survival of 28 patients with pancreatic cancer was studied following initial detection of this malignant neoplasm by ultrasonic scanning. By ultrasound examination, 24 patients had an abnormality, and 21 had a demonstrable mass. Twenty-seven patients are now deceased, and the overall survival ranged from eight days to 24 months (mean, 6.1 months). The results of this study indicate that diagnosis by ultrasonic scanning had no effect on the survival of patients with pancreatic carcinoma."}
{"id": "PMID:195100", "title": "Tangier disease (alpha-lipoprotein deficiency).", "content": "A patient with asymptomatic hypocholesterolemia, mild hyperbilirubinemia, and splenomegaly was found, on lipoprotein analysis, to have Tangier disease (alpha-lipoprotein deficiency). He represents the first patient with the disease in the northeastern Unit States. Although free of clinical evidence of atherosclerosis at age 38 years, the patient has widespread tissue cholesterol ester deposition and a stron family history of atherosclerosis. Tangier disease may be much underdiagnosed; it should be suspected in every patient with hypocholesterolemia.", "contents": "Tangier disease (alpha-lipoprotein deficiency). A patient with asymptomatic hypocholesterolemia, mild hyperbilirubinemia, and splenomegaly was found, on lipoprotein analysis, to have Tangier disease (alpha-lipoprotein deficiency). He represents the first patient with the disease in the northeastern Unit States. Although free of clinical evidence of atherosclerosis at age 38 years, the patient has widespread tissue cholesterol ester deposition and a stron family history of atherosclerosis. Tangier disease may be much underdiagnosed; it should be suspected in every patient with hypocholesterolemia."}
{"id": "PMID:195102", "title": "Human reovirus-like agent infection. Occurrence in adult contacts of pediatric patients with gastroenteritis.", "content": "Sixty-four adult family contacts of 61 young patients with gastroenteritis were included in a study for evidence of concurrent infection with the human reovirus-like agent (HRVLA) of infantile diarrhea. Evidence of infection was detected in 26 (41%) of the adult contacts. The HRVLA infection occurred significantly more often among adult contacts of pediatric patients infected with HRVLA (55%) than among contacts of young patients not infected with the agent (17%). Mild cases of gastroenteritis developed in only three of the contacts infected with HRVLA.", "contents": "Human reovirus-like agent infection. Occurrence in adult contacts of pediatric patients with gastroenteritis. Sixty-four adult family contacts of 61 young patients with gastroenteritis were included in a study for evidence of concurrent infection with the human reovirus-like agent (HRVLA) of infantile diarrhea. Evidence of infection was detected in 26 (41%) of the adult contacts. The HRVLA infection occurred significantly more often among adult contacts of pediatric patients infected with HRVLA (55%) than among contacts of young patients not infected with the agent (17%). Mild cases of gastroenteritis developed in only three of the contacts infected with HRVLA."}
{"id": "PMID:195103", "title": "Indications for liver and brain scans. Screening tests for patients with oat cell carcinoma of the lung.", "content": "From 1973 to 1975, scans of the liver and brain as routine screening procedures were performed on patients with oat cell carcinoma of the lung at the Memorial Sloan-Kettering Cancer Center. Normal test results were observed in 20 of 21 and 32 patients who showed no clinical evidence of involvement of the liver and brain. Only one scan in 21 and one in 35 yielded new information concerning possible organ involvement. We concluded that scans of the liver and brain are not useful methods of screening the patient with no clinical evidence of oat cell carcinoma.", "contents": "Indications for liver and brain scans. Screening tests for patients with oat cell carcinoma of the lung. From 1973 to 1975, scans of the liver and brain as routine screening procedures were performed on patients with oat cell carcinoma of the lung at the Memorial Sloan-Kettering Cancer Center. Normal test results were observed in 20 of 21 and 32 patients who showed no clinical evidence of involvement of the liver and brain. Only one scan in 21 and one in 35 yielded new information concerning possible organ involvement. We concluded that scans of the liver and brain are not useful methods of screening the patient with no clinical evidence of oat cell carcinoma."}
{"id": "PMID:195108", "title": "Peripheral nerve conduction velocities in chain-saw operators.", "content": "The motor, sensory and mixed nerve conduction velocities of median and posterior tibial nerves were measured in seventeen forest workers engaged in chain-saw operation for 2 to 16 yr (mean 12 yr). The conduction velocities were significantly diminished in the distal part of the upper limb. The sensory nerve conduction velocities (SCV) of the median nerve at the part of the palm were slow in 12 workers; longer residual latency, in 6; and the mixed nerve conduction velocities slowed at the part of the forearm, in 6. From the relationships of the nerve conduction velocities to white finger attacks and electromyograms, it was assumed that vibration directly affected the distal part of the sensory and motor nerve fibers in the upper limbs, and that the diminished SCV in the palm was one of the most sensitive indices of vibration effects.", "contents": "Peripheral nerve conduction velocities in chain-saw operators. The motor, sensory and mixed nerve conduction velocities of median and posterior tibial nerves were measured in seventeen forest workers engaged in chain-saw operation for 2 to 16 yr (mean 12 yr). The conduction velocities were significantly diminished in the distal part of the upper limb. The sensory nerve conduction velocities (SCV) of the median nerve at the part of the palm were slow in 12 workers; longer residual latency, in 6; and the mixed nerve conduction velocities slowed at the part of the forearm, in 6. From the relationships of the nerve conduction velocities to white finger attacks and electromyograms, it was assumed that vibration directly affected the distal part of the sensory and motor nerve fibers in the upper limbs, and that the diminished SCV in the palm was one of the most sensitive indices of vibration effects."}
{"id": "PMID:195113", "title": "Carcinoma arising in the cyst of the liver--report of three cases--.", "content": "A generally recognized concept dictates that surgical intervention for non-parasitic cysts of the liver is mostly palliative such as aspiration of the content, suture and closure, internal or external drainage, marsupialization, and unroofing of the cyst, while total excision of the entire cyst, which sometimes necessitates hepatic resection, is not usually recommended.3, 6, 9 The results of these lesser procedures have been acceptable, favoring those conservative procedures. This paper presents three cases with carcinoma arising in the cysts of the liver. Review of the present cases with five comparable cases appearing in the literature revealed that young female population and left lobe of the liver are frequently involved. Hence the general trend for palliative procedures should be reassessed. Possible malignancy should be considered when a patient belongs to this category, the cystic content is not clear, or the cystic wall presents irregular texture with nodules. The carcinomatous changes would have been of higher incidence than reported if the entire cysts had been more carefully examined.", "contents": "Carcinoma arising in the cyst of the liver--report of three cases--. A generally recognized concept dictates that surgical intervention for non-parasitic cysts of the liver is mostly palliative such as aspiration of the content, suture and closure, internal or external drainage, marsupialization, and unroofing of the cyst, while total excision of the entire cyst, which sometimes necessitates hepatic resection, is not usually recommended.3, 6, 9 The results of these lesser procedures have been acceptable, favoring those conservative procedures. This paper presents three cases with carcinoma arising in the cysts of the liver. Review of the present cases with five comparable cases appearing in the literature revealed that young female population and left lobe of the liver are frequently involved. Hence the general trend for palliative procedures should be reassessed. Possible malignancy should be considered when a patient belongs to this category, the cystic content is not clear, or the cystic wall presents irregular texture with nodules. The carcinomatous changes would have been of higher incidence than reported if the entire cysts had been more carefully examined."}
{"id": "PMID:195119", "title": "[Daily periods of aldosterone, sodium, and potassium excretion in the urine of newborns, infants, and children: influence of long-term steroid treatment and of the blockage of adrenergic beta-receptors (author's transl)].", "content": "Aldosterone, sodium, and potassium excretion in the urine of six newborns (5, 6, and 9 days), seven infants (2, 3, 4, and 6 months) and eight children (4, 5, 6, 12, and 15 years) was determined at 3-hour intervals during a 24-hour period via gas chromatography and/or flame photometry. The circadian rhythmn of aldosterone excretion could already be ascertained in the 5-day-old newborns. All babies and children examined showed a distinct increase in aldosterone excretion between 3 and 6 am or 6 and 9 am. On the overage, 41% of the total daily amount was excreted between 3 and 9 am. Excretion of sodium and potassium was very low for the newborns and infants. Only in small children and in school children did sodium excretion and the molecular relationship Na/k in urine have a statistically significant negative correlation with the excretion of aldosterone. After long-term prednisone therapy, the maximum amount of aldosterone was excreted in the afternoon. The findings after treatment with propranolol and administration of dexamethasone over a three-day period were similar.", "contents": "[Daily periods of aldosterone, sodium, and potassium excretion in the urine of newborns, infants, and children: influence of long-term steroid treatment and of the blockage of adrenergic beta-receptors (author's transl)]. Aldosterone, sodium, and potassium excretion in the urine of six newborns (5, 6, and 9 days), seven infants (2, 3, 4, and 6 months) and eight children (4, 5, 6, 12, and 15 years) was determined at 3-hour intervals during a 24-hour period via gas chromatography and/or flame photometry. The circadian rhythmn of aldosterone excretion could already be ascertained in the 5-day-old newborns. All babies and children examined showed a distinct increase in aldosterone excretion between 3 and 6 am or 6 and 9 am. On the overage, 41% of the total daily amount was excreted between 3 and 9 am. Excretion of sodium and potassium was very low for the newborns and infants. Only in small children and in school children did sodium excretion and the molecular relationship Na/k in urine have a statistically significant negative correlation with the excretion of aldosterone. After long-term prednisone therapy, the maximum amount of aldosterone was excreted in the afternoon. The findings after treatment with propranolol and administration of dexamethasone over a three-day period were similar."}
{"id": "PMID:195120", "title": "[Studies on the antimicrobial effect of vitamin D (author's transl)].", "content": "In in vitro studies vitamin D3 proved inhibitory on strains of Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae. Escherichia coli, and Candida albicans. In the presence of 5x10(4)-9x10(4) IU/ml vitamin D3 the organisms were killed or reacted with a marked growth inhibition.", "contents": "[Studies on the antimicrobial effect of vitamin D (author's transl)]. In in vitro studies vitamin D3 proved inhibitory on strains of Staphylococcus aureus, Streptococcus pyogenes, Klebsiella pneumoniae. Escherichia coli, and Candida albicans. In the presence of 5x10(4)-9x10(4) IU/ml vitamin D3 the organisms were killed or reacted with a marked growth inhibition."}
{"id": "PMID:195135", "title": "Viral infections of the captive Kenya baboon (Papio cynocephalus): a five-year epidemiologic study of an outdoor colony.", "content": "Rectal swabs, throat swabs, fecal samples, tissues, and sera were collected from 334 adult and infant Kenya baboons (Papio cynocephalus) in captivity at this institution over a 5-year period. A total of 4,893 specimens were collected, resulting in the isolation of 582 viral isolates (11.9%). The month of November yielded the lowest isolation rate, while the month of January produced the highest rate. The most commonly isolated viruses in adults and infants were SV6 and SV23, followed by N125, SV15, and SV17 in that order in adults, and SA7, N125, SV15, V340, and SV17 in that order in infants. Nine serotypes, namely enteroviruses SV19, SV42, SA5, A13, and N203, as well as adenoviruses SV15, SV20, SV31, and SV37, were isolated only from adults. Two adenovirus serotypes, SA7 and V340, were recovered predominantly from infants.", "contents": "Viral infections of the captive Kenya baboon (Papio cynocephalus): a five-year epidemiologic study of an outdoor colony. Rectal swabs, throat swabs, fecal samples, tissues, and sera were collected from 334 adult and infant Kenya baboons (Papio cynocephalus) in captivity at this institution over a 5-year period. A total of 4,893 specimens were collected, resulting in the isolation of 582 viral isolates (11.9%). The month of November yielded the lowest isolation rate, while the month of January produced the highest rate. The most commonly isolated viruses in adults and infants were SV6 and SV23, followed by N125, SV15, and SV17 in that order in adults, and SA7, N125, SV15, V340, and SV17 in that order in infants. Nine serotypes, namely enteroviruses SV19, SV42, SA5, A13, and N203, as well as adenoviruses SV15, SV20, SV31, and SV37, were isolated only from adults. Two adenovirus serotypes, SA7 and V340, were recovered predominantly from infants."}
{"id": "PMID:195136", "title": "Naturally occurring mouse hepatitis virus infection in the nude mouse.", "content": "A group of athymic nude mice developed an unusual chronic wasting disease within 1-3 months after their arrival into the laboratory. Affected nude mice had severe, acute-to-chronic, active hepatitis with multinucleated giant hepatocytes and fibrosis. Vascular and central nervous system lesions were frequently present, giant cell peritonitis, ascites, and multinucleated giant cells in the intestinal epithelial villi were less frequently observed. Mouse hepatitis virus was isolated from the livers of three mice with lesions. The virus, when inoculated into nude mice, produced lesions similar to those observed in the natural outbreak.", "contents": "Naturally occurring mouse hepatitis virus infection in the nude mouse. A group of athymic nude mice developed an unusual chronic wasting disease within 1-3 months after their arrival into the laboratory. Affected nude mice had severe, acute-to-chronic, active hepatitis with multinucleated giant hepatocytes and fibrosis. Vascular and central nervous system lesions were frequently present, giant cell peritonitis, ascites, and multinucleated giant cells in the intestinal epithelial villi were less frequently observed. Mouse hepatitis virus was isolated from the livers of three mice with lesions. The virus, when inoculated into nude mice, produced lesions similar to those observed in the natural outbreak."}
{"id": "PMID:195137", "title": "Experimental cytomegalovirus infection and the developing mouse inner ear: in vivo and in vitro studies.", "content": "Mouse cytomegalovirus causes perilabyrinthitis in the cochlea following intracranial inoculation of the newborn mouse. In spite of infection of cranial nerve ganglion cells and Schwann cells the organ of Corti achieves normal adult morphology including efferent nerve endings. No involvement of neuroaxons is seen. In comparison human cytomegalovirus infection causes endolabyrinthitis without involving periotic connective tissues or nerves even in the presence of meningoencephalitis. The lack of epithelial infection and susceptibility of periotic connective tissues to mouse cytomegalovirus was confirmed by infection of fetal mouse otocysts in organ culture. The mouse model of cytomegalovirus ear infection shows greater similarities to other herpesvirus infections of the ear such as varicella-zoster than to human cytomegalovirus and thus remains extremely useful for the study of herpetic neuronal and ear infection.", "contents": "Experimental cytomegalovirus infection and the developing mouse inner ear: in vivo and in vitro studies. Mouse cytomegalovirus causes perilabyrinthitis in the cochlea following intracranial inoculation of the newborn mouse. In spite of infection of cranial nerve ganglion cells and Schwann cells the organ of Corti achieves normal adult morphology including efferent nerve endings. No involvement of neuroaxons is seen. In comparison human cytomegalovirus infection causes endolabyrinthitis without involving periotic connective tissues or nerves even in the presence of meningoencephalitis. The lack of epithelial infection and susceptibility of periotic connective tissues to mouse cytomegalovirus was confirmed by infection of fetal mouse otocysts in organ culture. The mouse model of cytomegalovirus ear infection shows greater similarities to other herpesvirus infections of the ear such as varicella-zoster than to human cytomegalovirus and thus remains extremely useful for the study of herpetic neuronal and ear infection."}
{"id": "PMID:195141", "title": "Survival of patients with carcinoma of breast without lymph node metastases in relation to the tumor types.", "content": "Carcinoma of breast radical mastectomy specimens were examined. The tumors were classified in accordance with their morphologic appearance. The tumors were also graded on the basis of their cytological makeup and assigned a cytologic malignancy score (CMS). While the classification of tumors was based on the overall pattern of the tumor, the CMS was arrived at by examining the least differentiated portion of the tumor. The following conclusions were suggested by the study: Patients with tumors with high CMS have a poor prognosis, even in the absence of axillary lymph node metastases. It appears reasonable to suggest that patients without overt metastases, but with high CMS, should be considered for treatment with all therapeutic measures available. Such an aggressive approach to patients with low CMS does not appear to be justified.", "contents": "Survival of patients with carcinoma of breast without lymph node metastases in relation to the tumor types. Carcinoma of breast radical mastectomy specimens were examined. The tumors were classified in accordance with their morphologic appearance. The tumors were also graded on the basis of their cytological makeup and assigned a cytologic malignancy score (CMS). While the classification of tumors was based on the overall pattern of the tumor, the CMS was arrived at by examining the least differentiated portion of the tumor. The following conclusions were suggested by the study: Patients with tumors with high CMS have a poor prognosis, even in the absence of axillary lymph node metastases. It appears reasonable to suggest that patients without overt metastases, but with high CMS, should be considered for treatment with all therapeutic measures available. Such an aggressive approach to patients with low CMS does not appear to be justified."}
{"id": "PMID:195142", "title": "The histomorphologic spectrum of endocervical (M\u00fcllerian) adenocarcinoma--a potential prognostic indicator.", "content": "A review of all patients with endocervical adenocarcinoma seen at the Universtiy of Kentucky Medical Center from 1962 through 1972 yielded 15 patients with tissue-verifiable primary endocervical adenocarcinoma that had no associated sarcomatous or squamoid features. These patients varied from 17 to 73 years old with a mean age of 47 years. A malignant clear cell pattern was present in 8 patients and in 3 of these individuals that prominent morphologic feature was associated with hobnail cells. Five patients with clear cell carcinomatous changes in the endocervix were born prior to the use of diethylstilbestrol (DES) and 2 of the remaining 3 patients were exposed to DES during the first trimester of pregnancy. Other morphologic types of endocervical adenocarcinoma included mucinous adenocarcinoma in 9 patients (60%) and basaloid adenocarcinoma in one patient (7%). Cellular atypia of endocervical glands, which in some areas was consistent with adenocarcinoma in situ was found in 9 of the 15 patients with invasive endocervical cancers. Both vessel invasion by tumor cells and tumor necrosis were associated with a poor prognosis.", "contents": "The histomorphologic spectrum of endocervical (M\u00fcllerian) adenocarcinoma--a potential prognostic indicator. A review of all patients with endocervical adenocarcinoma seen at the Universtiy of Kentucky Medical Center from 1962 through 1972 yielded 15 patients with tissue-verifiable primary endocervical adenocarcinoma that had no associated sarcomatous or squamoid features. These patients varied from 17 to 73 years old with a mean age of 47 years. A malignant clear cell pattern was present in 8 patients and in 3 of these individuals that prominent morphologic feature was associated with hobnail cells. Five patients with clear cell carcinomatous changes in the endocervix were born prior to the use of diethylstilbestrol (DES) and 2 of the remaining 3 patients were exposed to DES during the first trimester of pregnancy. Other morphologic types of endocervical adenocarcinoma included mucinous adenocarcinoma in 9 patients (60%) and basaloid adenocarcinoma in one patient (7%). Cellular atypia of endocervical glands, which in some areas was consistent with adenocarcinoma in situ was found in 9 of the 15 patients with invasive endocervical cancers. Both vessel invasion by tumor cells and tumor necrosis were associated with a poor prognosis."}
{"id": "PMID:195143", "title": "[Krukenberg's tumor of the ovary].", "content": "A 42-year-old woman, 7 months after a gastric resection for carcinoma, again underwent surgery because in the area of the left adnexa she developed a tumor, the size of two fists. Laparotomy revealed a typical Krukenberg tumour in the left ovary only. The histological finding: carcinoma gelatinosum.", "contents": "[Krukenberg's tumor of the ovary]. A 42-year-old woman, 7 months after a gastric resection for carcinoma, again underwent surgery because in the area of the left adnexa she developed a tumor, the size of two fists. Laparotomy revealed a typical Krukenberg tumour in the left ovary only. The histological finding: carcinoma gelatinosum."}
{"id": "PMID:195146", "title": "Spontaneous mutations in ageing human cells: studies using a Herpesvirus probe.", "content": "Several fundamental theories of ageing postulate that spontaneous mutations increase in somatic cells as they age. This has not until recently been directly tested in mammalian cells, because of the problem of estimating mutation rate in declining cell populations. One possible approach is to infect cells with lytic virus and measure the mutation frequency in virus made by the cellular machinery. Three temperature-sensitive mutants of Herpesvirus were used to infect human fibroblasts in vitro. The reversion frequency was examined in virus harvested from young and old cells. It was found that with tsE there was a hundredfold increase in reversion rate in old compared to young cells, with tsD the rates were roughly similar and with tsG a fortyfold decrease in old cells. These differences are not due to differential rates of virus production. It is proposed that errors in specific functions in old cells influence the spontaneous mutation rate of the three viral mutants in opposite directions. It is pointed out that certain unknown factors limit the usefulness of viral probes in ageing research and cast doubt on previous work of this type.", "contents": "Spontaneous mutations in ageing human cells: studies using a Herpesvirus probe. Several fundamental theories of ageing postulate that spontaneous mutations increase in somatic cells as they age. This has not until recently been directly tested in mammalian cells, because of the problem of estimating mutation rate in declining cell populations. One possible approach is to infect cells with lytic virus and measure the mutation frequency in virus made by the cellular machinery. Three temperature-sensitive mutants of Herpesvirus were used to infect human fibroblasts in vitro. The reversion frequency was examined in virus harvested from young and old cells. It was found that with tsE there was a hundredfold increase in reversion rate in old compared to young cells, with tsD the rates were roughly similar and with tsG a fortyfold decrease in old cells. These differences are not due to differential rates of virus production. It is proposed that errors in specific functions in old cells influence the spontaneous mutation rate of the three viral mutants in opposite directions. It is pointed out that certain unknown factors limit the usefulness of viral probes in ageing research and cast doubt on previous work of this type."}
{"id": "PMID:195147", "title": "Somatic cell hybrids derived from terminally differentiated rhesus cells and established mouse cell lines.", "content": "The mechanisms of normal cell differentiation in vivo may be related to some features of cellular aging in vitro in that both are considered to be under genetic control. Diploid rhesus choroidal melanocytes and purified peripheral lymphocytes were fused by means of inactivated Sendai virus with three long-term murine cell lines which lacked either hypoxanthine-guanine phosphoribosyl transferase or thymidine kinase. Cell hybrids were selected by their growth in medium containing hypoxanthine, aminopterin, thymidine, and glycine. G-banded chromosomes were analyzed and elements from both the rhesus and the established mouse cell lines were identified in all metaphases. Hybrids derived from choroid X mouse cells contained more than one chromosome set from the mouse, but those between lymphocytes and established cell lines had only one. However, in every combination continuously replicating hybrids were produced; most of them have undergone more than 40 subculture passages. Our results demonstrate not only that DNA synthesis can be re-initiated in postreplicative cells, but also that DNA continues to replicate in a manner consistent with the life span of the long-term cell line parent.", "contents": "Somatic cell hybrids derived from terminally differentiated rhesus cells and established mouse cell lines. The mechanisms of normal cell differentiation in vivo may be related to some features of cellular aging in vitro in that both are considered to be under genetic control. Diploid rhesus choroidal melanocytes and purified peripheral lymphocytes were fused by means of inactivated Sendai virus with three long-term murine cell lines which lacked either hypoxanthine-guanine phosphoribosyl transferase or thymidine kinase. Cell hybrids were selected by their growth in medium containing hypoxanthine, aminopterin, thymidine, and glycine. G-banded chromosomes were analyzed and elements from both the rhesus and the established mouse cell lines were identified in all metaphases. Hybrids derived from choroid X mouse cells contained more than one chromosome set from the mouse, but those between lymphocytes and established cell lines had only one. However, in every combination continuously replicating hybrids were produced; most of them have undergone more than 40 subculture passages. Our results demonstrate not only that DNA synthesis can be re-initiated in postreplicative cells, but also that DNA continues to replicate in a manner consistent with the life span of the long-term cell line parent."}
{"id": "PMID:195167", "title": "[Acupuncture for pains of the face and the head is there any reasonable application? (author's transl)].", "content": "The physiological bases of the treatment with Acupuncture as well as its practical application in pain therapy were discussed at the meeting of the ORL-Society of Munich on the 4th December, 1976.", "contents": "[Acupuncture for pains of the face and the head is there any reasonable application? (author's transl)]. The physiological bases of the treatment with Acupuncture as well as its practical application in pain therapy were discussed at the meeting of the ORL-Society of Munich on the 4th December, 1976."}
{"id": "PMID:195168", "title": "[The clinical entity of primary tracheal cylindroma (author's transl)].", "content": "On the grounds of 5 own observations of primary tracheal cylindroma and under consideration of the cases mentioned in literature on this subject, the repeatingly occurring and, therefore, probably typical characteristics of this kind of tumour were described. In the course of the disease, three phases may quite easily be differentiated, and the special features of the main symptoms (dyspnoea, cough, expectoration, hoarseness) as well as apparently specific, however inconstant changes in the blood picture were set forth.", "contents": "[The clinical entity of primary tracheal cylindroma (author's transl)]. On the grounds of 5 own observations of primary tracheal cylindroma and under consideration of the cases mentioned in literature on this subject, the repeatingly occurring and, therefore, probably typical characteristics of this kind of tumour were described. In the course of the disease, three phases may quite easily be differentiated, and the special features of the main symptoms (dyspnoea, cough, expectoration, hoarseness) as well as apparently specific, however inconstant changes in the blood picture were set forth."}
{"id": "PMID:195179", "title": "Phentolamine prevents the somatostatin-mediated inhibition of pancreatic glucagon secretion.", "content": "This study was undertaken to assess the role of alpha-adrenergic receptors in the somatostatin-mediated inhibition of pancreatic glucagon secretion. In dogs, somatostatin inhibited the pancreatico-duodenal vein output of glucagon. During an infusion of the alpha-adrenergic blocking agent phentolamine, somatostatin did not significantly inhibit the output of glucagon. Thus, alpha-adrenergic mechanisms appear to influence the ability of somatostatin to decrease pancreatic glucagon secretion.", "contents": "Phentolamine prevents the somatostatin-mediated inhibition of pancreatic glucagon secretion. This study was undertaken to assess the role of alpha-adrenergic receptors in the somatostatin-mediated inhibition of pancreatic glucagon secretion. In dogs, somatostatin inhibited the pancreatico-duodenal vein output of glucagon. During an infusion of the alpha-adrenergic blocking agent phentolamine, somatostatin did not significantly inhibit the output of glucagon. Thus, alpha-adrenergic mechanisms appear to influence the ability of somatostatin to decrease pancreatic glucagon secretion."}
{"id": "PMID:195181", "title": "Prevalence of serum lipid abnormalities in chronic hemodialysis.", "content": "Fasting levels of serum triglyceride, cholesterol, high-density lipoprotein (HDL), apoprotein A-I, HDL cholesterol, and HDL triglyceride were measured in 94 uremic males receiving maintenance hemodialysis and 6 uremic males receiving chronic peritoneal dialysis. These patients had higher serum triglyceride levels (p less than 0.001) and lower cholesterol levels (p less than 0.001) than normal controls. The dialysis patients treated with androgen or propranolol and those who were hypothyroid or diabetic had significantly higher triglyceride levels than the other dialysis subjects. The dialysis patients who had no additional secondary causes of hypertriglyceridemia had abnormalities in HDL; in comparison to normals and triglyceride-matched controls, these patients had elevated HDL triglyceride levels and low HDL cholesterol levels, despite similar HDL apoprotein A-I levels. The HDL cholesterol levels appeared to be lower in those patients than could be accounted for by their degree of hypertriglyceridemia.", "contents": "Prevalence of serum lipid abnormalities in chronic hemodialysis. Fasting levels of serum triglyceride, cholesterol, high-density lipoprotein (HDL), apoprotein A-I, HDL cholesterol, and HDL triglyceride were measured in 94 uremic males receiving maintenance hemodialysis and 6 uremic males receiving chronic peritoneal dialysis. These patients had higher serum triglyceride levels (p less than 0.001) and lower cholesterol levels (p less than 0.001) than normal controls. The dialysis patients treated with androgen or propranolol and those who were hypothyroid or diabetic had significantly higher triglyceride levels than the other dialysis subjects. The dialysis patients who had no additional secondary causes of hypertriglyceridemia had abnormalities in HDL; in comparison to normals and triglyceride-matched controls, these patients had elevated HDL triglyceride levels and low HDL cholesterol levels, despite similar HDL apoprotein A-I levels. The HDL cholesterol levels appeared to be lower in those patients than could be accounted for by their degree of hypertriglyceridemia."}
{"id": "PMID:195183", "title": "Purification of herpesvirus nucleocapsids by fluorocarbon extraction.", "content": "Purified nucleocapsids were prepared from herpes simplex virus type-1 and herpes simplex virus type-2 infected cells, using a fluorocarbon extraction technique with Freon 113. Fifty to 85% of the total nucleocapsid population remained 'nucleated' or full in terms of the nucleic acid core making them useful as a source of DNA. CsCl banded DNA represented 30--40% of the theoretical yield of the total nucleocapsid population.", "contents": "Purification of herpesvirus nucleocapsids by fluorocarbon extraction. Purified nucleocapsids were prepared from herpes simplex virus type-1 and herpes simplex virus type-2 infected cells, using a fluorocarbon extraction technique with Freon 113. Fifty to 85% of the total nucleocapsid population remained 'nucleated' or full in terms of the nucleic acid core making them useful as a source of DNA. CsCl banded DNA represented 30--40% of the theoretical yield of the total nucleocapsid population."}
{"id": "PMID:195185", "title": "Studies on the neutralization of herpes simplex virus. VIII. Significance of viral sensitization for inactivation by complement.", "content": "Early and late IgG of rabbits immunized with herpes virus showed, respectively, 8-fold and 2-fold enhancement of neutralization endpoint in the presence of complement (C). Kinetic curve experiments employing an appropriate amount of virus revealed that both neutralization and sensitization followed first-order reaction, and each IgG possessed a certain range of concentration where neutralization was negligible while sensitization was marked. Dose responses of neutralization and sensitization velocities demonstrated that the C enhancement of late IgG was about 7-fold and that of early IgG more than 20-fold. These facts suggested that the IgGs contained two different entities of complement-requiring (CRN) and non-requiring neutralizing (N) antibodies at different proportions, only the former being responsible for sensitization. The different CRN: N ratios obtained by the endpoint and kinetic methods may mean either that the two antibodies differ in avidity for the virus or that the number of critical sites per virion for CRN antibody is greater than that for N antibody. In this interpretation, sensitization by CRN antibody as well as neutralization by N antibody is thought to result from attachment of a single antibody molecule to the viral critical site. Alternative explanations, ascribing the mechanism of neutralization to steric hindrance of critical sites or to multiple hit of those sites by antibody, were denied by analyses of the present data.", "contents": "Studies on the neutralization of herpes simplex virus. VIII. Significance of viral sensitization for inactivation by complement. Early and late IgG of rabbits immunized with herpes virus showed, respectively, 8-fold and 2-fold enhancement of neutralization endpoint in the presence of complement (C). Kinetic curve experiments employing an appropriate amount of virus revealed that both neutralization and sensitization followed first-order reaction, and each IgG possessed a certain range of concentration where neutralization was negligible while sensitization was marked. Dose responses of neutralization and sensitization velocities demonstrated that the C enhancement of late IgG was about 7-fold and that of early IgG more than 20-fold. These facts suggested that the IgGs contained two different entities of complement-requiring (CRN) and non-requiring neutralizing (N) antibodies at different proportions, only the former being responsible for sensitization. The different CRN: N ratios obtained by the endpoint and kinetic methods may mean either that the two antibodies differ in avidity for the virus or that the number of critical sites per virion for CRN antibody is greater than that for N antibody. In this interpretation, sensitization by CRN antibody as well as neutralization by N antibody is thought to result from attachment of a single antibody molecule to the viral critical site. Alternative explanations, ascribing the mechanism of neutralization to steric hindrance of critical sites or to multiple hit of those sites by antibody, were denied by analyses of the present data."}
{"id": "PMID:195186", "title": "Consumer evaluation of natural therapists and general practitioners.", "content": "In recent years orthodox medicine has been extensively criticized while alternative therapies have increasingly attracted the interest of patients. A consumer evaluation of alternative therapists and general practitioners is reported and implications are discussed. The study determined also that a significant number of the natural therapy patients felt their therapist provided a primary health care service. The characteristics of this group and reasons for their affiliation are considered.", "contents": "Consumer evaluation of natural therapists and general practitioners. In recent years orthodox medicine has been extensively criticized while alternative therapies have increasingly attracted the interest of patients. A consumer evaluation of alternative therapists and general practitioners is reported and implications are discussed. The study determined also that a significant number of the natural therapy patients felt their therapist provided a primary health care service. The characteristics of this group and reasons for their affiliation are considered."}
{"id": "PMID:195187", "title": "The mental health visitor and psychiatric after-care.", "content": "The results of a project, originating in South Australia, designed to assist the discharge of psychiatric patients are described. The project introduced a new category of mental health worker, the mental health visitor. These mature-age \"subprofessionals\" attached to social work departments after a brief, specific, in-service training, have worked closely with Mental Health Services psychiatrists, psychologists and social workers in various situations. They have established good relationships with social workers in other agencies and with general practitioners and their activities have included initial assessment, liaison and after-care. The demand for them appears to be increasing.", "contents": "The mental health visitor and psychiatric after-care. The results of a project, originating in South Australia, designed to assist the discharge of psychiatric patients are described. The project introduced a new category of mental health worker, the mental health visitor. These mature-age \"subprofessionals\" attached to social work departments after a brief, specific, in-service training, have worked closely with Mental Health Services psychiatrists, psychologists and social workers in various situations. They have established good relationships with social workers in other agencies and with general practitioners and their activities have included initial assessment, liaison and after-care. The demand for them appears to be increasing."}
{"id": "PMID:195190", "title": "Clinical evaluation of prophylactic intranasal 1-phenyl-3-(4-phenyl-2-thiazolyl) guanidine (CL 88,277) medication against rhinovirus 44 challenge.", "content": "The prophylactic intranasal medication with a new antiviral compound, 1-phenyl-3-(4 phenyl-2-thiazolyl) guanidine (CL 88,277) was evaluated in humans against rhinovirus 44 challenge. One ml containing 250 mg of CL 88,277 was administered to 10 seronegative volunteers three times a day plus one dose prior to the rhinovirus challenge (32 TCID 50) and for six consecutive post-challenge days. Ten other subjects received 56% polyethylene glycol (PEG-400), the solvent of CL 88,277 at the same time. Five subjects in each of the CL 88,277-treated and placebo-treated groups developed illness. There were no differences between the two groups in the occurrence of the severe illness and of the moderate and severe illnesses. Each sign and symptom occurred almost equally in the two groups and there was no difference in their scores between the two groups. The challenge virus was isolated from both groups but the total number of the virus isolates was less and the time span of virus excretion was shorter for the drug-treated group. The post-challenge serum antibody titers were markedly lower in the drug-treated group. Prophylactic intranasal CL 88,277 medication did not affect the course of illness induced by rhinovirus 44 challenge. It appears, however, that the virus replication in the nose was reduced and as a result the serum antibody response was diminished. PEG-400 caused a transient irritation of the nasal mucosa in all recipients.", "contents": "Clinical evaluation of prophylactic intranasal 1-phenyl-3-(4-phenyl-2-thiazolyl) guanidine (CL 88,277) medication against rhinovirus 44 challenge. The prophylactic intranasal medication with a new antiviral compound, 1-phenyl-3-(4 phenyl-2-thiazolyl) guanidine (CL 88,277) was evaluated in humans against rhinovirus 44 challenge. One ml containing 250 mg of CL 88,277 was administered to 10 seronegative volunteers three times a day plus one dose prior to the rhinovirus challenge (32 TCID 50) and for six consecutive post-challenge days. Ten other subjects received 56% polyethylene glycol (PEG-400), the solvent of CL 88,277 at the same time. Five subjects in each of the CL 88,277-treated and placebo-treated groups developed illness. There were no differences between the two groups in the occurrence of the severe illness and of the moderate and severe illnesses. Each sign and symptom occurred almost equally in the two groups and there was no difference in their scores between the two groups. The challenge virus was isolated from both groups but the total number of the virus isolates was less and the time span of virus excretion was shorter for the drug-treated group. The post-challenge serum antibody titers were markedly lower in the drug-treated group. Prophylactic intranasal CL 88,277 medication did not affect the course of illness induced by rhinovirus 44 challenge. It appears, however, that the virus replication in the nose was reduced and as a result the serum antibody response was diminished. PEG-400 caused a transient irritation of the nasal mucosa in all recipients."}
{"id": "PMID:195199", "title": "[Ultrastructure of cytoplasmic deposits and enzyme studies in human primary liver cancer].", "content": "Authors examined of the fine structure and electronhistochemical properties of deposits observed in two cases of primary liver carcinoma. It was established, that these deposits are formed by filaments consisting of fine granules of 70 A in diameter. On the basis of morphological picture and results of the investigation by enzymatic-dogestion technique it is believed, that deposits are the product of the rough-surfaced endoplasmic reticulum and their occurrence indicate the impairment of it's function. Deposits--as revealed by the enzymatic-digestion technique--consists of complex material, the protein component of which contain large quantities of basical amino acids.", "contents": "[Ultrastructure of cytoplasmic deposits and enzyme studies in human primary liver cancer]. Authors examined of the fine structure and electronhistochemical properties of deposits observed in two cases of primary liver carcinoma. It was established, that these deposits are formed by filaments consisting of fine granules of 70 A in diameter. On the basis of morphological picture and results of the investigation by enzymatic-dogestion technique it is believed, that deposits are the product of the rough-surfaced endoplasmic reticulum and their occurrence indicate the impairment of it's function. Deposits--as revealed by the enzymatic-digestion technique--consists of complex material, the protein component of which contain large quantities of basical amino acids."}
{"id": "PMID:195200", "title": "[Advances in the treatment of malignant tumors in childhood: Wilm's tumor as an example (author's transl)].", "content": "The advances in the treatment of the Wilm's tumor have been made both surgically and in the conservative field. Extirpation through a lateral incision has given way to the broad transabdominal exposure. Inoperable tumors are very rare. Cytostatics like actinomycin D and vincristine are already applied intraoperatively. The choice of cytostatic and the duration of cytostatic therapy is adjusted to the intraoperative staging. The Society for Pediatric Oncology has worked out a modified plan of treatment in accordance with the growth of the tumor, in addition irradiation is applied according to the tumor staging. The results are stated as between 60 and 70%, the histology of the tumor and the age of the child, in addition to the growth of the tumor, being especially important.", "contents": "[Advances in the treatment of malignant tumors in childhood: Wilm's tumor as an example (author's transl)]. The advances in the treatment of the Wilm's tumor have been made both surgically and in the conservative field. Extirpation through a lateral incision has given way to the broad transabdominal exposure. Inoperable tumors are very rare. Cytostatics like actinomycin D and vincristine are already applied intraoperatively. The choice of cytostatic and the duration of cytostatic therapy is adjusted to the intraoperative staging. The Society for Pediatric Oncology has worked out a modified plan of treatment in accordance with the growth of the tumor, in addition irradiation is applied according to the tumor staging. The results are stated as between 60 and 70%, the histology of the tumor and the age of the child, in addition to the growth of the tumor, being especially important."}
{"id": "PMID:195201", "title": "[Treatment of primary hyperlipoproteinemias of type IIB and IV with butylbiguanide and clofibrate (author's transl)].", "content": "21 patients with primary hyperlipoproteinemias of type IIb and IV were treated for 8 weeks with placebo, 8 weeks with 0.3 g butylbiguanide and 1.5 g clofibrate/day and then for 8 weeks with 1.5 g clofibrate/day. In 12 patients a second placebo phase of 8 weeks followed. After 8 weeks of combined treatment with butylbiguanide and clofibrate the serum triglycerides decreased from 725 mg to 269 mg/100 ml. During the following period of clofibrate treatment the serum triglycerides increased after 4 and 8 weeks to 326 mg and 306 mg/100 ml respectively. The combined treatment with 0.3 g butylbiguanide and 1.5 g clofibrate/day is more effective in lowering elevated serum triglycerides and cholesterol than 1.5 g clofibrate alone.", "contents": "[Treatment of primary hyperlipoproteinemias of type IIB and IV with butylbiguanide and clofibrate (author's transl)]. 21 patients with primary hyperlipoproteinemias of type IIb and IV were treated for 8 weeks with placebo, 8 weeks with 0.3 g butylbiguanide and 1.5 g clofibrate/day and then for 8 weeks with 1.5 g clofibrate/day. In 12 patients a second placebo phase of 8 weeks followed. After 8 weeks of combined treatment with butylbiguanide and clofibrate the serum triglycerides decreased from 725 mg to 269 mg/100 ml. During the following period of clofibrate treatment the serum triglycerides increased after 4 and 8 weeks to 326 mg and 306 mg/100 ml respectively. The combined treatment with 0.3 g butylbiguanide and 1.5 g clofibrate/day is more effective in lowering elevated serum triglycerides and cholesterol than 1.5 g clofibrate alone."}
{"id": "PMID:195203", "title": "Accentuated vascular and endocrine response to SQ 20881 in hypertension.", "content": "We assessed vascular and hormonal responses to inhibition of peptidyldipeptide hydrolase, which converts angiotensin I to angiotensin II (converting enzyme) and degrades bradykinin (kininase II), in subjects given 10 meq of sodium to activate both systems. In nine normal subjects a threshold dose of 30 MICROgram per kilogram of the inhibitor, SQ 20881, modestly influenced mean blood pressure (-5 +/- 1 mm Hg, P less than 0.05), and renal blood flow (+50+/-8 ml per 100 g per minute), plasma renin activity (+ 2.3 +/- 0.6 ng per milliliter per hour), and angiotensin II (-11 +/- 3 pg per milliliter) more strikingly (P less than 0.01). In six patients with essential hypertension the threshold inhibitor dose was reduced to 10 microgram per kilogram; 30 kilogram per kilogram had an enhanced (P less than 0.01) effect on mean blood pressure (-11 +/- 2 mm Hg), renal blood flow (137 +/- 20 ml per 100 g per minute), and angiotensin II concentration (-29 +/- 12 pg per milliliter). SQ 20881 elevated plasma bradykinin concentration (7.4 +/- 2.6 ng per milliliter, P less than 0.02) only in the hypertensive patients. Because both renin-angiotensin and kallikrein-bradykinin systems are influenced, vascular responses to SQ 20881 must be interpreted cautiously, but this agent has excellent antihypertensive characteristics.", "contents": "Accentuated vascular and endocrine response to SQ 20881 in hypertension. We assessed vascular and hormonal responses to inhibition of peptidyldipeptide hydrolase, which converts angiotensin I to angiotensin II (converting enzyme) and degrades bradykinin (kininase II), in subjects given 10 meq of sodium to activate both systems. In nine normal subjects a threshold dose of 30 MICROgram per kilogram of the inhibitor, SQ 20881, modestly influenced mean blood pressure (-5 +/- 1 mm Hg, P less than 0.05), and renal blood flow (+50+/-8 ml per 100 g per minute), plasma renin activity (+ 2.3 +/- 0.6 ng per milliliter per hour), and angiotensin II (-11 +/- 3 pg per milliliter) more strikingly (P less than 0.01). In six patients with essential hypertension the threshold inhibitor dose was reduced to 10 microgram per kilogram; 30 kilogram per kilogram had an enhanced (P less than 0.01) effect on mean blood pressure (-11 +/- 2 mm Hg), renal blood flow (137 +/- 20 ml per 100 g per minute), and angiotensin II concentration (-29 +/- 12 pg per milliliter). SQ 20881 elevated plasma bradykinin concentration (7.4 +/- 2.6 ng per milliliter, P less than 0.02) only in the hypertensive patients. Because both renin-angiotensin and kallikrein-bradykinin systems are influenced, vascular responses to SQ 20881 must be interpreted cautiously, but this agent has excellent antihypertensive characteristics."}
{"id": "PMID:195206", "title": "Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child.", "content": "We investigated an immunodeficient child in whom chronic progressive poliomyelitis developed after she had received live oral poliovirus vaccine. Poliovirus, Type II, was isolated from throat and stool during life and from several sites within the brain at autopsy. The brain isolate was classified as vaccine-like on the basis of temperature sensitivity and antigenic markers. However, in the monkey neurovirulence test, the brain isolate produced moderately severe lesions throughout the spinal cord and brainstem and appeared nonvaccine-like. Thus, the brain isolate demonstrated a dissociation between the antigenic and neurovirulence markers. Our observations suggest that, under unusual circumstances, such as immunodeficiency, attenuated poliovirus can produce a chronic progressive neurologic disease. This case also emphasizes the need to diagnose immunodeficiency as early as possible, so that live-virus vaccines will not be administered.", "contents": "Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child. We investigated an immunodeficient child in whom chronic progressive poliomyelitis developed after she had received live oral poliovirus vaccine. Poliovirus, Type II, was isolated from throat and stool during life and from several sites within the brain at autopsy. The brain isolate was classified as vaccine-like on the basis of temperature sensitivity and antigenic markers. However, in the monkey neurovirulence test, the brain isolate produced moderately severe lesions throughout the spinal cord and brainstem and appeared nonvaccine-like. Thus, the brain isolate demonstrated a dissociation between the antigenic and neurovirulence markers. Our observations suggest that, under unusual circumstances, such as immunodeficiency, attenuated poliovirus can produce a chronic progressive neurologic disease. This case also emphasizes the need to diagnose immunodeficiency as early as possible, so that live-virus vaccines will not be administered."}
{"id": "PMID:195207", "title": "Recommendations for a national policy on poliomyelitis vaccination.", "content": "Declining numbers of adequately vaccinated persons, new data about the comparative safety and effectiveness of live, attenuated and killed poliomyelitis-virus vaccines, increased consumer awareness of adverse reactions and pressure from manufacturers seeking protection from liability were factors leading the Institute of Medicine to re-examine poliomyelitis vaccination programs. The relative merits of live and killed virus vaccines as immunizing agents were reviewed within the context of the 60 to 70 per cent level of poliomyelitis vaccination now reached in the United States. Until about 90 per cent of persons are adequately immunized, the continued use of live-virus vaccines for infants is recommended, with provision that certain categories of persons receive killed-virus vaccine. Vaccination with attenuated live virus of children 11 to 12 years old is suggested to reduce vaccine-associated disease when they become parents of vaccinated infants. Recommendations are made on education, research, liability and informed consent as they pertain to prevention of polyomyelitis.", "contents": "Recommendations for a national policy on poliomyelitis vaccination. Declining numbers of adequately vaccinated persons, new data about the comparative safety and effectiveness of live, attenuated and killed poliomyelitis-virus vaccines, increased consumer awareness of adverse reactions and pressure from manufacturers seeking protection from liability were factors leading the Institute of Medicine to re-examine poliomyelitis vaccination programs. The relative merits of live and killed virus vaccines as immunizing agents were reviewed within the context of the 60 to 70 per cent level of poliomyelitis vaccination now reached in the United States. Until about 90 per cent of persons are adequately immunized, the continued use of live-virus vaccines for infants is recommended, with provision that certain categories of persons receive killed-virus vaccine. Vaccination with attenuated live virus of children 11 to 12 years old is suggested to reduce vaccine-associated disease when they become parents of vaccinated infants. Recommendations are made on education, research, liability and informed consent as they pertain to prevention of polyomyelitis."}
{"id": "PMID:195208", "title": "Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study.", "content": "We evaluated adenine arabinoside (vidarabine) for treatment of herpes simplex encephalitis in a placebo-controlled study. In 28 cases proved by isolation of Type 1 virus from brain biopsy, treatment reduced mortality from 70 to 28 per cent (P = 0.03), and over 50 per cent of treated survivors had no or only moderately debilitating neurologic sequelae. This improvement was achieved without evidence of acute drug toxicity. Thus, adenine arabinoside has a good therapeutic index (efficacy/toxicity) for the treatment of Type 1 herpes simplex encephalitis. However, the drug must be given early in the course of infection before the advent of coma to have a beneficial effect. Moreover, it should be coupled with brain biopsy for specific diagnosis to avoid unnecessary treatment of nonresponsive encephalitides that can mimic herpes simplex.", "contents": "Adenine arabinoside therapy of biopsy-proved herpes simplex encephalitis. National Institute of Allergy and Infectious Diseases collaborative antiviral study. We evaluated adenine arabinoside (vidarabine) for treatment of herpes simplex encephalitis in a placebo-controlled study. In 28 cases proved by isolation of Type 1 virus from brain biopsy, treatment reduced mortality from 70 to 28 per cent (P = 0.03), and over 50 per cent of treated survivors had no or only moderately debilitating neurologic sequelae. This improvement was achieved without evidence of acute drug toxicity. Thus, adenine arabinoside has a good therapeutic index (efficacy/toxicity) for the treatment of Type 1 herpes simplex encephalitis. However, the drug must be given early in the course of infection before the advent of coma to have a beneficial effect. Moreover, it should be coupled with brain biopsy for specific diagnosis to avoid unnecessary treatment of nonresponsive encephalitides that can mimic herpes simplex."}
{"id": "PMID:195217", "title": "Endogenous opioid peptides: multiple agonists and receptors.", "content": "Opioid peptides were assayed by inhibition of 3H-naloxone and 3H-leu-enkephalin binding in brain homogenates and by depression of contractions of the guinea pig ileum and mouse vas deferens. We conclude that the opioid peptidergic system has agonists of different characteristics which interact with more than one type of receptor.", "contents": "Endogenous opioid peptides: multiple agonists and receptors. Opioid peptides were assayed by inhibition of 3H-naloxone and 3H-leu-enkephalin binding in brain homogenates and by depression of contractions of the guinea pig ileum and mouse vas deferens. We conclude that the opioid peptidergic system has agonists of different characteristics which interact with more than one type of receptor."}
{"id": "PMID:195227", "title": "Presence of beta-adrenoreceptors in the hypothalamus; their importance for the pressor response to hypothalamic stimulation.", "content": "The posterior hypothalamus of cats anaesthetized with pentobarbital sodium was superfused and electrically stimulated with a push-pull cannula. Superfusion of the hypothalamus with (+/-)-, (-)-propranolol, sotalol, practolol or metoprolol caused a concentration-dependent inhibiton of the pressor response to hypothalamic stimulation. (+/-)-Propranolol and a procaine concentration equi-anaesthetic to the concentration of (+/-)- and (-)-propranolol were ineffective. Lower concentrations of propranolol and metoprolol were needed to inhibit the pressor response than of sotalol or practolol. Superfusion with practolol and tolazoline impaired the pressor response to a greater extent than did superfusion with each of the drugs alone. Hypothalamic superfusion with isoproterenol elicited a concentration-dependent enhancement of the rise of blood pressure during electrical stimulation of the hypothalamus. It is concluded that beta-adrenorecptors are present in the posterior hypothalamus and that they are involved in the pressor response elicited by electrical stimulation of the hypothalamus. Propranolol and metoprolol seemed to possess a higher affinity to the beta-receptors of the hypothalamus than sotalol or practolol.", "contents": "Presence of beta-adrenoreceptors in the hypothalamus; their importance for the pressor response to hypothalamic stimulation. The posterior hypothalamus of cats anaesthetized with pentobarbital sodium was superfused and electrically stimulated with a push-pull cannula. Superfusion of the hypothalamus with (+/-)-, (-)-propranolol, sotalol, practolol or metoprolol caused a concentration-dependent inhibiton of the pressor response to hypothalamic stimulation. (+/-)-Propranolol and a procaine concentration equi-anaesthetic to the concentration of (+/-)- and (-)-propranolol were ineffective. Lower concentrations of propranolol and metoprolol were needed to inhibit the pressor response than of sotalol or practolol. Superfusion with practolol and tolazoline impaired the pressor response to a greater extent than did superfusion with each of the drugs alone. Hypothalamic superfusion with isoproterenol elicited a concentration-dependent enhancement of the rise of blood pressure during electrical stimulation of the hypothalamus. It is concluded that beta-adrenorecptors are present in the posterior hypothalamus and that they are involved in the pressor response elicited by electrical stimulation of the hypothalamus. Propranolol and metoprolol seemed to possess a higher affinity to the beta-receptors of the hypothalamus than sotalol or practolol."}
{"id": "PMID:195228", "title": "Acetylcholine and cAMP in adrenal medulla:indirect effect.", "content": "Catecholamine release and cAMP accumulation were studied in bovine adrenal medulla slices in vitro. Acetylcholine (10(-4) M) and salbutamol (10(-6) M) caused increased release of catecholamines and accumulation of cAMP. Incubation in Ca2+ -free medium abolished the release of catecholamines and the increase of cAMP caused by acetylcholine but not that caused by salbutamol. In a membrane fraction of adrenal medulla acetylcholine (10(-4) M) had no effect on adenylate cyclase activity but salbutamol (10(-6) M) caused substantial activation of adenylate cyclase. It is suggested that acetylcholine has no direct effect on adenylate cyclase or cAMP in adrenal medulla and the accumulation of cAMP observed in slices incubated with acetylcholine is due to the effect of catecholamines, released by acetylcholine, on the medullary cells.", "contents": "Acetylcholine and cAMP in adrenal medulla:indirect effect. Catecholamine release and cAMP accumulation were studied in bovine adrenal medulla slices in vitro. Acetylcholine (10(-4) M) and salbutamol (10(-6) M) caused increased release of catecholamines and accumulation of cAMP. Incubation in Ca2+ -free medium abolished the release of catecholamines and the increase of cAMP caused by acetylcholine but not that caused by salbutamol. In a membrane fraction of adrenal medulla acetylcholine (10(-4) M) had no effect on adenylate cyclase activity but salbutamol (10(-6) M) caused substantial activation of adenylate cyclase. It is suggested that acetylcholine has no direct effect on adenylate cyclase or cAMP in adrenal medulla and the accumulation of cAMP observed in slices incubated with acetylcholine is due to the effect of catecholamines, released by acetylcholine, on the medullary cells."}
{"id": "PMID:195234", "title": "Aphasia in multiple sclerosis.", "content": "In a 17-year-old woman, motor aphasia developed during her second bout of multiple sclerosis, characterized by absent spontaneous speech, paraphasias in naming and repetition, and marked orofacial apraxia, with relative preservation of written language and intact auditory comprehension. A mild right hemiparesis was associated. Bilateral cerebral lesions were demonstrated on a computerized tomographic brain scan. The aphasia remitted over 1 month.", "contents": "Aphasia in multiple sclerosis. In a 17-year-old woman, motor aphasia developed during her second bout of multiple sclerosis, characterized by absent spontaneous speech, paraphasias in naming and repetition, and marked orofacial apraxia, with relative preservation of written language and intact auditory comprehension. A mild right hemiparesis was associated. Bilateral cerebral lesions were demonstrated on a computerized tomographic brain scan. The aphasia remitted over 1 month."}
{"id": "PMID:195235", "title": "Alexia without agraphia, hemianopia, or color-naming defect: a disconnection syndrome.", "content": "A patient with alexia without agraphia, hemianopia, or color-naming defect was found at operation to have a meningioma arising from the tentorium cerebelli that compressed the inferior aspect of the left temporal-occipital junction. It is presumed to have involved only the left ventral visual association cortex and its inferior outflow tracts to the angular gyrus. The input from the right occipital area also was disconnected from the visual language verbal association area by involvement of the ventral outflow of the splenium of the corpus callosum. Preservation of color naming and matching suggests that these functions are dependent on the integrity of more dorsal occipital association systems.", "contents": "Alexia without agraphia, hemianopia, or color-naming defect: a disconnection syndrome. A patient with alexia without agraphia, hemianopia, or color-naming defect was found at operation to have a meningioma arising from the tentorium cerebelli that compressed the inferior aspect of the left temporal-occipital junction. It is presumed to have involved only the left ventral visual association cortex and its inferior outflow tracts to the angular gyrus. The input from the right occipital area also was disconnected from the visual language verbal association area by involvement of the ventral outflow of the splenium of the corpus callosum. Preservation of color naming and matching suggests that these functions are dependent on the integrity of more dorsal occipital association systems."}
{"id": "PMID:195232", "title": "Facts and reflections on thalamocortical reverberation of impulses.", "content": "Experiments on cats, either unanesthetized or anesthetized with various doses of pentobarbital, showed that the cortical rhythmic after-discharge (\"slow after-activity\"), which has been regarded as a manifestation of reverberation of impulses in thalamocortical circuits [17], consists of a burst of spontaneous \"spindles\" evoked by stimulation. This conclusion is supported by the following facts: Spontaneous \"spindles\" and the rhythmic after-discharge respond absolutely identically (disappear) to activation of the EEG and deepening of pentobarbital anesthesia. The absence of thalamocortical reverberation is also indicated by the preservation of a rhythmic after-discharge (to clicks), synchronous with the cortex, in the thalamic relay nucleus (the medial geniculate body) after cooling or after removal of its projection zone.", "contents": "Facts and reflections on thalamocortical reverberation of impulses. Experiments on cats, either unanesthetized or anesthetized with various doses of pentobarbital, showed that the cortical rhythmic after-discharge (\"slow after-activity\"), which has been regarded as a manifestation of reverberation of impulses in thalamocortical circuits [17], consists of a burst of spontaneous \"spindles\" evoked by stimulation. This conclusion is supported by the following facts: Spontaneous \"spindles\" and the rhythmic after-discharge respond absolutely identically (disappear) to activation of the EEG and deepening of pentobarbital anesthesia. The absence of thalamocortical reverberation is also indicated by the preservation of a rhythmic after-discharge (to clicks), synchronous with the cortex, in the thalamic relay nucleus (the medial geniculate body) after cooling or after removal of its projection zone."}
{"id": "PMID:195236", "title": "Encephalopathy associated with lamellar residual bodies in astrocytes (Towfighi, Grover and Gonatas 1975):a new observation.", "content": "A 7-year-old male patient presented a few episodes of convulsions during the first year of life. The psychomotor development has been normal during that period of time after which a steadily progressive deterioration occurred. Increasingly severe pyramidal signs, optic atrophy, quadriparesis and progressive evolution towards a decorticate state were noted. Skin and neuromuscular biopsies were not contributory. A brain biopsy showed the presence of lamellar inclusions in astrocytes and, to a lesser extent, in neurons. Such features have only been reported once in two siblings by Towfighi et al. (1975). The nosological situation of this disease is discussed.", "contents": "Encephalopathy associated with lamellar residual bodies in astrocytes (Towfighi, Grover and Gonatas 1975):a new observation. A 7-year-old male patient presented a few episodes of convulsions during the first year of life. The psychomotor development has been normal during that period of time after which a steadily progressive deterioration occurred. Increasingly severe pyramidal signs, optic atrophy, quadriparesis and progressive evolution towards a decorticate state were noted. Skin and neuromuscular biopsies were not contributory. A brain biopsy showed the presence of lamellar inclusions in astrocytes and, to a lesser extent, in neurons. Such features have only been reported once in two siblings by Towfighi et al. (1975). The nosological situation of this disease is discussed."}
{"id": "PMID:195233", "title": "Synaptic processes in pericruciate cortical neurons evoked by pyramidal tract stimulation in cats.", "content": "In cats anesthetized with chloralose and pentobarbital and immobilized with D-tubocurarine activity of 423 pericruciate cortical neurons was recorded (342 extra- and 81 intracellularly); 78 neurons had spontaneous activity. Stimulation of the pyramidal tract evoked antidromic action potentials in the pyramidal neurons with a latent period of 0.5-16.0 msec. Recurrent and lateral PSPs also developed both in pyramidal and in unidentified neurons in all layers of the cortex; IPSPs were recorded in 46.7% of neurons, EPSPs in 21.0%, mixed responses in 26.0%, and no visible changes were found in 6.3%. The latent period of the IPSPs was 1.5-14.0 msec, ther amplitude 1.3-17.0 mV, their rise time from 4 to 18 msec, and their duration 18-120 msec (sometimes up to 250-500 msec). In 30% of cases in which IPSPs appeared, their course was divided into two phases: fast (duration 10-20 msec) and slow. EPSPs developed after a latent period of 2.6-29.0 msec; their amplitude was 1.0-7.8 mV and their duration from 10.0 to 50.0 msec. In 51.2% of spontaneously active neurons the antidromic volley inhibited their activity in the course of 200-400 msec, in 19.5% it stimulated their activity, in 7.4% it had a mixed effect, and in 21.9% no visible change took place in their activity. The role and participation of axon collaterals of pyramidal neurons and of the interneuronal system in the formation of these processes are discussed.", "contents": "Synaptic processes in pericruciate cortical neurons evoked by pyramidal tract stimulation in cats. In cats anesthetized with chloralose and pentobarbital and immobilized with D-tubocurarine activity of 423 pericruciate cortical neurons was recorded (342 extra- and 81 intracellularly); 78 neurons had spontaneous activity. Stimulation of the pyramidal tract evoked antidromic action potentials in the pyramidal neurons with a latent period of 0.5-16.0 msec. Recurrent and lateral PSPs also developed both in pyramidal and in unidentified neurons in all layers of the cortex; IPSPs were recorded in 46.7% of neurons, EPSPs in 21.0%, mixed responses in 26.0%, and no visible changes were found in 6.3%. The latent period of the IPSPs was 1.5-14.0 msec, ther amplitude 1.3-17.0 mV, their rise time from 4 to 18 msec, and their duration 18-120 msec (sometimes up to 250-500 msec). In 30% of cases in which IPSPs appeared, their course was divided into two phases: fast (duration 10-20 msec) and slow. EPSPs developed after a latent period of 2.6-29.0 msec; their amplitude was 1.0-7.8 mV and their duration from 10.0 to 50.0 msec. In 51.2% of spontaneously active neurons the antidromic volley inhibited their activity in the course of 200-400 msec, in 19.5% it stimulated their activity, in 7.4% it had a mixed effect, and in 21.9% no visible change took place in their activity. The role and participation of axon collaterals of pyramidal neurons and of the interneuronal system in the formation of these processes are discussed."}
{"id": "PMID:195239", "title": "The Brenner tumor: a clinicopathologic review.", "content": "The Brenner tumor of the ovary has been the topic of voluminous clinical and pathologic literature since its original description by Macnaughton-Jones in 1898. One of the major problems confronting most investigators of this uncommon neoplasm has been the question of histogenesis. There is general agreement that the tumor is derived from surface (coelomic) epithelium, as are the serous and mucinous cystadenomas. Most Brenner tumors are asymptomatic except for some which have features suggestive of estrogen production. The major pathologic variants are the proliferating and the malignant Brenner tumors; a poor prognosis is associated with the latter neoplasm. Approximately 30% of all benign Brenner tumors have a second histologic type of tumor in the ipsilateral or contralateral ovary, a serous or mucinous cystadenoma in most cases. Brenner tumors have also been reported in the broad ligament and in the testis on rare occasions.", "contents": "The Brenner tumor: a clinicopathologic review. The Brenner tumor of the ovary has been the topic of voluminous clinical and pathologic literature since its original description by Macnaughton-Jones in 1898. One of the major problems confronting most investigators of this uncommon neoplasm has been the question of histogenesis. There is general agreement that the tumor is derived from surface (coelomic) epithelium, as are the serous and mucinous cystadenomas. Most Brenner tumors are asymptomatic except for some which have features suggestive of estrogen production. The major pathologic variants are the proliferating and the malignant Brenner tumors; a poor prognosis is associated with the latter neoplasm. Approximately 30% of all benign Brenner tumors have a second histologic type of tumor in the ipsilateral or contralateral ovary, a serous or mucinous cystadenoma in most cases. Brenner tumors have also been reported in the broad ligament and in the testis on rare occasions."}
{"id": "PMID:195240", "title": "Thecomas and granulosa-theca cell tumors of the ovary: an analysis of 51 tumors,.", "content": "A retrospective study of 51 thecomas and granulosa-theca cell tumors of the ovary seen at Confederate Memorial Medical Center in Shreveport, Louisiana, is presented. Endometrial tissue was available for study in 38 of the 51 patients. The relation of these tumors to endometrial morphology suggests an excessive estrogenic stimulation in most cases. The microscopic pattern and degree of pleomorphism was of no value in predicting which tumors would behave in a malignant fashion. The incidence of endometrial malignancy associated with these tumors was only 7.8%, which was less than was anticipated. The addition of irradiation and/or chemotherapy is, in our opinion, difficult to evaluate since many of the women with these tumors die of unrelated causes before a recurrence is evident.", "contents": "Thecomas and granulosa-theca cell tumors of the ovary: an analysis of 51 tumors,. A retrospective study of 51 thecomas and granulosa-theca cell tumors of the ovary seen at Confederate Memorial Medical Center in Shreveport, Louisiana, is presented. Endometrial tissue was available for study in 38 of the 51 patients. The relation of these tumors to endometrial morphology suggests an excessive estrogenic stimulation in most cases. The microscopic pattern and degree of pleomorphism was of no value in predicting which tumors would behave in a malignant fashion. The incidence of endometrial malignancy associated with these tumors was only 7.8%, which was less than was anticipated. The addition of irradiation and/or chemotherapy is, in our opinion, difficult to evaluate since many of the women with these tumors die of unrelated causes before a recurrence is evident."}
{"id": "PMID:195242", "title": "Human chorionic gonadotropin and its subunits in hydatidiform mole and choriocarcinoma.", "content": "Serum human chorionic gonadotropin (hCG) was measured by a radioreceptorassay (RRA) and radioimmunoassay (RIA) and serum hCG-beta and hCG-alpha by RIA in 10 patients with intact mole, 3 patients with choriocarcinoma, and 4 patients with hydatidiform mole during treatment. hCG levels by RRA were higher in 5 of 10 molar pregnancies and ranged from 20,900 to 100,000 ng/ml and from 30,000 to 100,000 ng/ml by RIA. hCG levels by RRA and RIA paralleled one another closely during treatment of hydatidiform mole. hCG-alpha was higher than hCG by RRA and RIA and hCG-beta in molar pregnancies, in the uterine venous blood draining a uterine choriocarcinoma, and during chemotherapy of choriocarcinoma. In 2 of 3 choriocarcinoma patients who eventually developed cerebral metastases, hCG-alpha increased while hCG and hCG-beta were declining or negative. hCG-beta was usually lower than hCG or hCG-alpha in all the cases studied. These results demonstrate the production of free alpha and beta subunits in trophoblastic disease. Further, due to the biospecificity, simplicity, and rapidity, the RRA of hCG is a sueful diagnostic aid during treatment of trophoblastic neoplasia until the levels fall to within the sensitivity range of the assay. Finally, the RIA of hCG, hCG-beta, and hCG-alpha, which requires several days, should be performed until they become negative or fall within normal range.", "contents": "Human chorionic gonadotropin and its subunits in hydatidiform mole and choriocarcinoma. Serum human chorionic gonadotropin (hCG) was measured by a radioreceptorassay (RRA) and radioimmunoassay (RIA) and serum hCG-beta and hCG-alpha by RIA in 10 patients with intact mole, 3 patients with choriocarcinoma, and 4 patients with hydatidiform mole during treatment. hCG levels by RRA were higher in 5 of 10 molar pregnancies and ranged from 20,900 to 100,000 ng/ml and from 30,000 to 100,000 ng/ml by RIA. hCG levels by RRA and RIA paralleled one another closely during treatment of hydatidiform mole. hCG-alpha was higher than hCG by RRA and RIA and hCG-beta in molar pregnancies, in the uterine venous blood draining a uterine choriocarcinoma, and during chemotherapy of choriocarcinoma. In 2 of 3 choriocarcinoma patients who eventually developed cerebral metastases, hCG-alpha increased while hCG and hCG-beta were declining or negative. hCG-beta was usually lower than hCG or hCG-alpha in all the cases studied. These results demonstrate the production of free alpha and beta subunits in trophoblastic disease. Further, due to the biospecificity, simplicity, and rapidity, the RRA of hCG is a sueful diagnostic aid during treatment of trophoblastic neoplasia until the levels fall to within the sensitivity range of the assay. Finally, the RIA of hCG, hCG-beta, and hCG-alpha, which requires several days, should be performed until they become negative or fall within normal range."}
{"id": "PMID:195252", "title": "[Comparative study of the multiple molecular forms of NAD-dependent glutamate dehydrogenase in the liver and femoral muscle at different stages of swine embryogenesis[].", "content": "The multiplicity of NAD-dependent glutamate dehydrogenase (GDH) was studied in the liver and femoral muscle of 30, 60 and 108 days old pig embryos by the method of discelectrophoresis in polyacrilamide gel. The GDH was shown to be presented in the tissues under study by 3--4 multiple molecular forms. Specific ratios of the multiple GDH forms were established in the tissues under study at different stages of embryogenesis.", "contents": "[Comparative study of the multiple molecular forms of NAD-dependent glutamate dehydrogenase in the liver and femoral muscle at different stages of swine embryogenesis[]. The multiplicity of NAD-dependent glutamate dehydrogenase (GDH) was studied in the liver and femoral muscle of 30, 60 and 108 days old pig embryos by the method of discelectrophoresis in polyacrilamide gel. The GDH was shown to be presented in the tissues under study by 3--4 multiple molecular forms. Specific ratios of the multiple GDH forms were established in the tissues under study at different stages of embryogenesis."}
{"id": "PMID:195255", "title": "Mechanosensitivity of dorsal root ganglia and chronically injured axons: a physiological basis for the radicular pain of nerve root compression.", "content": "The radicular pain of sciatica was ascribed by Mixter and Barr to compression of the spinal root by a herniated intervertebral disc. It was assumed that root compression produced prolonged firing in the injured sensory fibers and led to pain perceived in the peripheral distribution of those fibers. This concept has been challenged on the basis that acute peripheral nerve compression neuropathies are usually painless. Furthermore, animal experiments have rarely shown more than several seconds of repetitive firing in acutely compressed nerves or nerve roots. It has been suggested that \"radicular pain\" is actually pain referred to the extremity through activation of deep spinal and paraspinal nociceptors. Our experiments on cat lumbar dorsal roots and rabbit sural nerves have confirmed that acute compression of the root or nerve does not produce more than several seconds of repetitive firing. However, long periods of repetitive firing (5-25 min) follow minimal acute compression of the normal dorsal root ganglion. Chronic injury of dorsal roots or sural nerve produces a marked increase in mechanical sensitivity; several minutes of repetitive firing may follow acute compression of such chronically injured sites. Such prolonged responses could be evoked repeatedly in a population of both rapidly and slowly conducting fibers. Since mechanical compression of either the dorsal root ganglion or of chronically injured roots can induce prolonged repetitive firing in sensory axons, we conclude that radicular pain is due to activity in the fibers appropriate to the area of perceived pain.", "contents": "Mechanosensitivity of dorsal root ganglia and chronically injured axons: a physiological basis for the radicular pain of nerve root compression. The radicular pain of sciatica was ascribed by Mixter and Barr to compression of the spinal root by a herniated intervertebral disc. It was assumed that root compression produced prolonged firing in the injured sensory fibers and led to pain perceived in the peripheral distribution of those fibers. This concept has been challenged on the basis that acute peripheral nerve compression neuropathies are usually painless. Furthermore, animal experiments have rarely shown more than several seconds of repetitive firing in acutely compressed nerves or nerve roots. It has been suggested that \"radicular pain\" is actually pain referred to the extremity through activation of deep spinal and paraspinal nociceptors. Our experiments on cat lumbar dorsal roots and rabbit sural nerves have confirmed that acute compression of the root or nerve does not produce more than several seconds of repetitive firing. However, long periods of repetitive firing (5-25 min) follow minimal acute compression of the normal dorsal root ganglion. Chronic injury of dorsal roots or sural nerve produces a marked increase in mechanical sensitivity; several minutes of repetitive firing may follow acute compression of such chronically injured sites. Such prolonged responses could be evoked repeatedly in a population of both rapidly and slowly conducting fibers. Since mechanical compression of either the dorsal root ganglion or of chronically injured roots can induce prolonged repetitive firing in sensory axons, we conclude that radicular pain is due to activity in the fibers appropriate to the area of perceived pain."}
{"id": "PMID:195256", "title": "A new technique for recording of intradental sensory nerve activity in man.", "content": "A technique was developed to record intradental sensory nerve activity in man. The method involves permanent fixation of electrodes in dentin thus enabling continuous recordings to be made. Acute as well as long term influences on excitability of sensory nerve endings in the tooth can thus be studied. A coincidence between recorded spike activity and pain sensation was observed.", "contents": "A new technique for recording of intradental sensory nerve activity in man. A technique was developed to record intradental sensory nerve activity in man. The method involves permanent fixation of electrodes in dentin thus enabling continuous recordings to be made. Acute as well as long term influences on excitability of sensory nerve endings in the tooth can thus be studied. A coincidence between recorded spike activity and pain sensation was observed."}
{"id": "PMID:195257", "title": "[Copper and nervous system. An experimental study (author's transl)].", "content": "Sodium azide is known to produce alterations in mammalian copper proteins, thus rendering them unable to bind exogenous metal, which remains in the \"labile pool\" condition. Continuous administration of sodium azide at LD50 for 30 days causes copper accumulation in several tissues and even in the nervous system, with characteristic changes in neurones and glial cells, very much resembling the alterations observed in Wilson's disease. Dietary copper administration, on the contrary, though raising the level of tissue-bound metal, does not produce cellular damage. These findings allow us to suppose that sodium azide may alterate the coppper chelating proteins in the tissues, especially in the nervous system, thus causing the storage of cell-toxic \"labile pool\" metal. The pathogenesis of Wilson's disease and the problem of \"pathoclisis\" in the nervous system are debated.", "contents": "[Copper and nervous system. An experimental study (author's transl)]. Sodium azide is known to produce alterations in mammalian copper proteins, thus rendering them unable to bind exogenous metal, which remains in the \"labile pool\" condition. Continuous administration of sodium azide at LD50 for 30 days causes copper accumulation in several tissues and even in the nervous system, with characteristic changes in neurones and glial cells, very much resembling the alterations observed in Wilson's disease. Dietary copper administration, on the contrary, though raising the level of tissue-bound metal, does not produce cellular damage. These findings allow us to suppose that sodium azide may alterate the coppper chelating proteins in the tissues, especially in the nervous system, thus causing the storage of cell-toxic \"labile pool\" metal. The pathogenesis of Wilson's disease and the problem of \"pathoclisis\" in the nervous system are debated."}
{"id": "PMID:195258", "title": "Familial abdominal chemodectomas with associated cutaneous angiolipomas.", "content": "The occurrence of cutaneous angiolipomas and intra-abdominal retroperitoneal chemodectomas in two brothers is described. Both died from malignant dissemination of the chemodectomas. It is possible but speculative that two other brothers suffered from the same syndrome.", "contents": "Familial abdominal chemodectomas with associated cutaneous angiolipomas. The occurrence of cutaneous angiolipomas and intra-abdominal retroperitoneal chemodectomas in two brothers is described. Both died from malignant dissemination of the chemodectomas. It is possible but speculative that two other brothers suffered from the same syndrome."}
{"id": "PMID:195261", "title": "Phosphatidylcholine-lysophosphatidylcholine cycle pathway enzymes in rabbit lung. I. Subcellular localization and properties.", "content": "The de novo cytidine-5'-diphosphocholine (CDP-choline) pathway enzymes: choline kinase (CK); phosphorylcholine cytidyltransferase (CyT), and phosphorylcholine glyceride transferase (PCGT), and the phosphatidylcholine-lysophosphatidylcholine (PC-lysolPC) cycle pathway enzymes: lysophospholipase (LPL), lysophosphatidylcholine-lysophosphatidylcholine acyltransferase (LAT), and acyl-CoA lysophosphatidylcholine acyltransferase (acyl-CoA LAT) were studied in the rabbit lung subcellular fractions. The purity of the fractions was examined by the marker enzymes and electron microscopy. The lamellar bodies had the highest concentration of phospholipids (10.0 mumol/mg protein, 80% of which was phosphatidylcholine (PC), about 10-fold higher than that of mitochondria (0.8) and microsomes (1.0) (50% of which was PC in both fractions). The lamellar bodies contained no enzymic activities of either the CDP-choline pathway or the PC-lysoPC cycle pathway. The enzymic activities of CK, CyT, LPL, and LAT were found mainly in the soluble fraction (about 40% for CK and CyT, and 70% for LPL and LAT); PCGT and acyl-CoA LAT were microsomal enzymes. Some general properties of PC-lysoPC cycle enzymes were also studied. The activities of LPL, LAT, and acyl-CoA LAT were not stimulated by the divalent metal ion Ca+. Their activities were inhibited by 10(-3) M diisopropyl phosphorofluoridate (DFP). The role of the PC-lysoPC cycle pathway enzymes in remodeling the lung PC is discussed.", "contents": "Phosphatidylcholine-lysophosphatidylcholine cycle pathway enzymes in rabbit lung. I. Subcellular localization and properties. The de novo cytidine-5'-diphosphocholine (CDP-choline) pathway enzymes: choline kinase (CK); phosphorylcholine cytidyltransferase (CyT), and phosphorylcholine glyceride transferase (PCGT), and the phosphatidylcholine-lysophosphatidylcholine (PC-lysolPC) cycle pathway enzymes: lysophospholipase (LPL), lysophosphatidylcholine-lysophosphatidylcholine acyltransferase (LAT), and acyl-CoA lysophosphatidylcholine acyltransferase (acyl-CoA LAT) were studied in the rabbit lung subcellular fractions. The purity of the fractions was examined by the marker enzymes and electron microscopy. The lamellar bodies had the highest concentration of phospholipids (10.0 mumol/mg protein, 80% of which was phosphatidylcholine (PC), about 10-fold higher than that of mitochondria (0.8) and microsomes (1.0) (50% of which was PC in both fractions). The lamellar bodies contained no enzymic activities of either the CDP-choline pathway or the PC-lysoPC cycle pathway. The enzymic activities of CK, CyT, LPL, and LAT were found mainly in the soluble fraction (about 40% for CK and CyT, and 70% for LPL and LAT); PCGT and acyl-CoA LAT were microsomal enzymes. Some general properties of PC-lysoPC cycle enzymes were also studied. The activities of LPL, LAT, and acyl-CoA LAT were not stimulated by the divalent metal ion Ca+. Their activities were inhibited by 10(-3) M diisopropyl phosphorofluoridate (DFP). The role of the PC-lysoPC cycle pathway enzymes in remodeling the lung PC is discussed."}
{"id": "PMID:195262", "title": "Phosphatidylcholine-lysophosphatidylcholine cycle pathway enzymes in rabbit lung. II. Marked differences in the effect of gestational age on activity compared to the CDP-choline pathway.", "content": "Lysophosphatidylcholine (lysoPC), a breakdown product of phosphatidylcholine (PC), might be important in pulmonary PC synthesis through fatty acid exchange reactions. This study defines the levels of three of the enzymes of the PC-lysoPC cycle pathway (lysophospholipase (LPL) (EC. 3.1.1.5), lysophosphatidylcholine-lysophosphatidylcholine acyltransferase (LAT), and acyl-CoA lysophosphatidylcholine acyltransferase (acryl-CoA LAT) (EC. 2.3.1.23)) in developing fetal rabbit lung and compared them with the enzymes of the CPD-choline synthetic pathway (choline kinase (CK) (EC. 2.7.1.32), phosphorylcholine cytidyl transferase (CyT) (EC. 2.7.7.15), and phosphorylcholine glyceride transferase (PCGT) (EC. 2.7.8.2). Lung homogenates of fetal rabbits of known gestation, newborn, and adult rabbits were used for the enzyme, protein, and phospholipid analyses. Total lung phospholipid, PC, and protein increased with gestational age. Thirty days' gestation, newborn, and maternal lung activities of CK, CyT, and PCGT had decreased to only 50% of their activities at 22-26 days' gestation. In contrast, LPL and LAT activities increased 4-5-fold from 22-26 days to 30 days' gestation, and increased further in the newborn lung, finally to a level matching maternal lung (about 8-10-fold higher than the 22-26 days' gestation activities). The microsomal acyl-CoA LAT also showed a similar increasing activity with gestational age. In fetal lung, enzymic activities for the apparent major PC synthetic pathway decreased. In contrast, the marked increases in LPL, LAT, and acyl-CoA LAT activities with increasing gestational age and at birth suggests importance of the PC lysoPC cycle pathway in regulating synthesis and turnover with maturation.", "contents": "Phosphatidylcholine-lysophosphatidylcholine cycle pathway enzymes in rabbit lung. II. Marked differences in the effect of gestational age on activity compared to the CDP-choline pathway. Lysophosphatidylcholine (lysoPC), a breakdown product of phosphatidylcholine (PC), might be important in pulmonary PC synthesis through fatty acid exchange reactions. This study defines the levels of three of the enzymes of the PC-lysoPC cycle pathway (lysophospholipase (LPL) (EC. 3.1.1.5), lysophosphatidylcholine-lysophosphatidylcholine acyltransferase (LAT), and acyl-CoA lysophosphatidylcholine acyltransferase (acryl-CoA LAT) (EC. 2.3.1.23)) in developing fetal rabbit lung and compared them with the enzymes of the CPD-choline synthetic pathway (choline kinase (CK) (EC. 2.7.1.32), phosphorylcholine cytidyl transferase (CyT) (EC. 2.7.7.15), and phosphorylcholine glyceride transferase (PCGT) (EC. 2.7.8.2). Lung homogenates of fetal rabbits of known gestation, newborn, and adult rabbits were used for the enzyme, protein, and phospholipid analyses. Total lung phospholipid, PC, and protein increased with gestational age. Thirty days' gestation, newborn, and maternal lung activities of CK, CyT, and PCGT had decreased to only 50% of their activities at 22-26 days' gestation. In contrast, LPL and LAT activities increased 4-5-fold from 22-26 days to 30 days' gestation, and increased further in the newborn lung, finally to a level matching maternal lung (about 8-10-fold higher than the 22-26 days' gestation activities). The microsomal acyl-CoA LAT also showed a similar increasing activity with gestational age. In fetal lung, enzymic activities for the apparent major PC synthetic pathway decreased. In contrast, the marked increases in LPL, LAT, and acyl-CoA LAT activities with increasing gestational age and at birth suggests importance of the PC lysoPC cycle pathway in regulating synthesis and turnover with maturation."}
{"id": "PMID:195265", "title": "Antibody persistence after primary immunization with trivalent oral poliovirus vaccine.", "content": "Five years after primary infant immunization with trivalent oral poliovirus vaccine, employing either a three-dose primary series as recommended by the U.S. Public Health Service Advisory Committee on Immunization Practices (ACIP) or a four-dose series as recommended by the Committee on Infectious Diseases of the American Academy of Pediatrics. 115 children were serologically tested for persistence of neutralizing antibodies by the microneutralization test. Of the 57 individuals immunized according to the ACIP recommendation, antibody persistence was demonstrated in 92% for type 1 poliovirus, 98% for type 2, and 84% for type 3. Of those 58 individuals originally receiving a four-dose primary infant immunization series, the persistence of antibody was 98% to type 1, 98% to type 2, and 87% to type 3. Twenty-one of 24 negative sera showed neutralizing ability when tested by a more sensitive plaque reduction test. Thus, individuals completing either immunization schedule demonstrated satisfactory persistence of neutralizing antibody to all three poliovirus types over a five-year period.", "contents": "Antibody persistence after primary immunization with trivalent oral poliovirus vaccine. Five years after primary infant immunization with trivalent oral poliovirus vaccine, employing either a three-dose primary series as recommended by the U.S. Public Health Service Advisory Committee on Immunization Practices (ACIP) or a four-dose series as recommended by the Committee on Infectious Diseases of the American Academy of Pediatrics. 115 children were serologically tested for persistence of neutralizing antibodies by the microneutralization test. Of the 57 individuals immunized according to the ACIP recommendation, antibody persistence was demonstrated in 92% for type 1 poliovirus, 98% for type 2, and 84% for type 3. Of those 58 individuals originally receiving a four-dose primary infant immunization series, the persistence of antibody was 98% to type 1, 98% to type 2, and 87% to type 3. Twenty-one of 24 negative sera showed neutralizing ability when tested by a more sensitive plaque reduction test. Thus, individuals completing either immunization schedule demonstrated satisfactory persistence of neutralizing antibody to all three poliovirus types over a five-year period."}
{"id": "PMID:195268", "title": "REM and dreaming.", "content": "4 subjects were awakened after long REM periods and 12 other subjects after short REM and after NREMs. The mean numbers of words, dream episodes, and spontaneous remarks about being interrupted in the middle of a dream were significantly different in the reports of the three groups. It is suggested that the present view of the relationship between REM and dreaming is not conclusive.", "contents": "REM and dreaming. 4 subjects were awakened after long REM periods and 12 other subjects after short REM and after NREMs. The mean numbers of words, dream episodes, and spontaneous remarks about being interrupted in the middle of a dream were significantly different in the reports of the three groups. It is suggested that the present view of the relationship between REM and dreaming is not conclusive."}
{"id": "PMID:195269", "title": "Inhibitory effect of methylxanthines on feedback control of glomerular filtration rate in the rat kidney.", "content": "Microperfusion experiments were performed in rats to assess the effect of luminal application of theophylline and the more lipophilic 3-isobutyl-1-methylxanthine (IBMX) on feedback regulation of glomerular filtration rate. Elevation of loop of Henle flow from 0 to 40 nl/min caused a 20.3 +/- 4.5% reduction of stop flow pressure (SFP) and a 32.2 +/- 3.7% reduction of early proximal flow rate (EPFR) when the perfusate was a 140 mM NaCl solution. When theophylline was added in a concentration of 5mM SFP fell by only 5.3 +/- 1.8% and EPFR by 7.9 +/- 33%, changes which were significantly smaller than in the control perfusions (P less than 0.01). An identical change of loop of Henle flow in the presence of IBMX in concentration of 1 and 5 mM was associated with a 4.5 +/- 3.9% decrease and a 12.1 +/- 2.7% increase of EPFR. In orthograde perfusion experiments full inhibition of the feedback response was noted at an IBMX concentration of about 1 mM while during retrograde perfusion a concentration of 0.4 mM was sufficient to produce the same effect. This indicates that methylxanthines diffuse out of the loop of Henle to a considerable extent. Methylxanthines reduced absolute and fractional water absorption along the loop of Henle to some extent while Cl absorption rates and early distal Cl concentrations were not significantly altered. Cyclic AMP applied from the luminal side in a concentration of 10 mM did not affect the feedback response of EPFR to flow elevation from 0 to 40 nl/min. Luminal application of dibutyryl cyclic AMP at 10 mM induced a small, but significant reduction of the feedback response when tested by paired t-test (P less than 0.05). Our results show that luminal application of methylxanthines strongly interfere with feedback regulation of glomerular filtration rate. It is unclear at present whether this effect is related to inhibition of cyclic nucleotide phosphodiesterase and a rise in tissue cyclic AMP levels or to interference with a mechanism involving the local action of adenosine or 5'-AMP.", "contents": "Inhibitory effect of methylxanthines on feedback control of glomerular filtration rate in the rat kidney. Microperfusion experiments were performed in rats to assess the effect of luminal application of theophylline and the more lipophilic 3-isobutyl-1-methylxanthine (IBMX) on feedback regulation of glomerular filtration rate. Elevation of loop of Henle flow from 0 to 40 nl/min caused a 20.3 +/- 4.5% reduction of stop flow pressure (SFP) and a 32.2 +/- 3.7% reduction of early proximal flow rate (EPFR) when the perfusate was a 140 mM NaCl solution. When theophylline was added in a concentration of 5mM SFP fell by only 5.3 +/- 1.8% and EPFR by 7.9 +/- 33%, changes which were significantly smaller than in the control perfusions (P less than 0.01). An identical change of loop of Henle flow in the presence of IBMX in concentration of 1 and 5 mM was associated with a 4.5 +/- 3.9% decrease and a 12.1 +/- 2.7% increase of EPFR. In orthograde perfusion experiments full inhibition of the feedback response was noted at an IBMX concentration of about 1 mM while during retrograde perfusion a concentration of 0.4 mM was sufficient to produce the same effect. This indicates that methylxanthines diffuse out of the loop of Henle to a considerable extent. Methylxanthines reduced absolute and fractional water absorption along the loop of Henle to some extent while Cl absorption rates and early distal Cl concentrations were not significantly altered. Cyclic AMP applied from the luminal side in a concentration of 10 mM did not affect the feedback response of EPFR to flow elevation from 0 to 40 nl/min. Luminal application of dibutyryl cyclic AMP at 10 mM induced a small, but significant reduction of the feedback response when tested by paired t-test (P less than 0.05). Our results show that luminal application of methylxanthines strongly interfere with feedback regulation of glomerular filtration rate. It is unclear at present whether this effect is related to inhibition of cyclic nucleotide phosphodiesterase and a rise in tissue cyclic AMP levels or to interference with a mechanism involving the local action of adenosine or 5'-AMP."}
{"id": "PMID:195270", "title": "Aspartate and other inhibitors of excitatory synaptic transmission in crayfish muscle.", "content": "Synaptic currents were measured in voltage clamped crayfish muscle fibers which were triggered either by stimulation of the motor axon (EPSC), or by L-gutamate (gEPSC) applied by microiontophoresis or superfusion. Among a number of analogues of glutamate, L-glutamic-acid-gamma-methyl ester, L-glutamic-acid-dimethyl ester and L-aspartate, were reasonably specific antagonists at the motor synapses, although at relatively high concentrations. Aslo, 2-amino-4-phosphono-butyric acid and morphine were effective antagonists; the action of morphine, however, seemed to be unspecific. Aspartate was further shown to decrease the size of the quantum EPSC, without affecting the probability of release of transmitter or the potential change recorded from the presynaptic nerve terminal. The results also indicate that aspartate, after longer incubations, is released as a false transmitter. The dose-response curve to short glutamate pulse is shifted by aspartate to higher glutamate concentrations, without affecting the steep slope of the dose-response curve or the saturation level. This effect can be interpreted as competitive inhibition by aspartate, with an equilibrium concentration of aspartate at the receptor of 0.3--1.5 mmol/l. In longer glutamate applications the receptor desensitizes rapidly. Aspartate reduces this desensitization in addition to its competitive inhibitory effect. Suppression of desensitization can be more effective than inhibition in long glutamate applications; in this case aspartate apparently potentiates the effects of glutamate.", "contents": "Aspartate and other inhibitors of excitatory synaptic transmission in crayfish muscle. Synaptic currents were measured in voltage clamped crayfish muscle fibers which were triggered either by stimulation of the motor axon (EPSC), or by L-gutamate (gEPSC) applied by microiontophoresis or superfusion. Among a number of analogues of glutamate, L-glutamic-acid-gamma-methyl ester, L-glutamic-acid-dimethyl ester and L-aspartate, were reasonably specific antagonists at the motor synapses, although at relatively high concentrations. Aslo, 2-amino-4-phosphono-butyric acid and morphine were effective antagonists; the action of morphine, however, seemed to be unspecific. Aspartate was further shown to decrease the size of the quantum EPSC, without affecting the probability of release of transmitter or the potential change recorded from the presynaptic nerve terminal. The results also indicate that aspartate, after longer incubations, is released as a false transmitter. The dose-response curve to short glutamate pulse is shifted by aspartate to higher glutamate concentrations, without affecting the steep slope of the dose-response curve or the saturation level. This effect can be interpreted as competitive inhibition by aspartate, with an equilibrium concentration of aspartate at the receptor of 0.3--1.5 mmol/l. In longer glutamate applications the receptor desensitizes rapidly. Aspartate reduces this desensitization in addition to its competitive inhibitory effect. Suppression of desensitization can be more effective than inhibition in long glutamate applications; in this case aspartate apparently potentiates the effects of glutamate."}
{"id": "PMID:195278", "title": "Acrylamide poisoning.", "content": "A small epidemic of acrylamide poisoning amongst workers in the construction industry is described. The clinical features of this condition are reviewed and two cases are described in which residual neurological problems persisted for over 1 year. The literature on acrylamide poisoning is reviewed and it is recommended that this substance should only be handled in the open air or in well ventilated areas. Its use in confined spaces such as tunnels appears to be unduly hazardous.", "contents": "Acrylamide poisoning. A small epidemic of acrylamide poisoning amongst workers in the construction industry is described. The clinical features of this condition are reviewed and two cases are described in which residual neurological problems persisted for over 1 year. The literature on acrylamide poisoning is reviewed and it is recommended that this substance should only be handled in the open air or in well ventilated areas. Its use in confined spaces such as tunnels appears to be unduly hazardous."}
{"id": "PMID:195279", "title": "Gynaecomastia associated with gonadotrophin-secreting carcinoma of the lung.", "content": "A 67-year-old man developed dermatomyositis. Investigation revealed an oat cell carcinoma of the lung. When he developed unilateral gynaecomastia this tumour was found to secrete gonadotrophins. The gynaecomastia disappeared after treatment with an anti-oestrogen--tamoxifen. This use of tamoxifen has not previously been described. Partial tumour regression was obtained with several cytotoxic drug regimes. His dermatomyositis responded to this treatment and remains in remission.", "contents": "Gynaecomastia associated with gonadotrophin-secreting carcinoma of the lung. A 67-year-old man developed dermatomyositis. Investigation revealed an oat cell carcinoma of the lung. When he developed unilateral gynaecomastia this tumour was found to secrete gonadotrophins. The gynaecomastia disappeared after treatment with an anti-oestrogen--tamoxifen. This use of tamoxifen has not previously been described. Partial tumour regression was obtained with several cytotoxic drug regimes. His dermatomyositis responded to this treatment and remains in remission."}
{"id": "PMID:195281", "title": "[Effect of thermal load and ACTH administration on the ATPase activity of homogenates and microsomal fractions of the tissues of growing rats].", "content": "A study was made of the age dynamics of the ATP-ase activity in the homogenates and the microsomal fractions of the liver, kidneys, brain and muscles of albino rats. It was shown that in young animals the change of the ATP-ase activity in the tissues (the index of energy metabolism) in response to the ACTH administal life the shifts in the ATP-ase activity of different tissues after the thermal stress and administration of ACTH proved to vary in character.", "contents": "[Effect of thermal load and ACTH administration on the ATPase activity of homogenates and microsomal fractions of the tissues of growing rats]. A study was made of the age dynamics of the ATP-ase activity in the homogenates and the microsomal fractions of the liver, kidneys, brain and muscles of albino rats. It was shown that in young animals the change of the ATP-ase activity in the tissues (the index of energy metabolism) in response to the ACTH administal life the shifts in the ATP-ase activity of different tissues after the thermal stress and administration of ACTH proved to vary in character."}
{"id": "PMID:195280", "title": "[Effect of insulin on the reactivity of the myocardium to hydrocortisone].", "content": "Experiments were conducted on rats. A study was made (with the aid of histological and histochemical methods) of the effect of administration of hydrocortisone, insulin, and also of the combined administration of these hormones on the myocardial structure and metabolism. Hydrocortisone administration for 30 days proved to derange the metabolism and to cause dystrophic changes in the myocardium. In combined administration of hydrocortisone and insulin these dystrophic changes were much less pronounced.", "contents": "[Effect of insulin on the reactivity of the myocardium to hydrocortisone]. Experiments were conducted on rats. A study was made (with the aid of histological and histochemical methods) of the effect of administration of hydrocortisone, insulin, and also of the combined administration of these hormones on the myocardial structure and metabolism. Hydrocortisone administration for 30 days proved to derange the metabolism and to cause dystrophic changes in the myocardium. In combined administration of hydrocortisone and insulin these dystrophic changes were much less pronounced."}
{"id": "PMID:195292", "title": "Rehabilitation program following polycentric total knee arthroplasty.", "content": "A rehabilitation program which has been used successfully in improving the postoperative range of motion of patient undergoing total knee arthroplasty is outlined. The specific objectives are strong quadriceps setting, straight leg raising, flexion of the knee to at least 90 degrees, and extension of the knee to 0 degrees. The program emphasizes the importance of early institution of exercises and early ambulation.", "contents": "Rehabilitation program following polycentric total knee arthroplasty. A rehabilitation program which has been used successfully in improving the postoperative range of motion of patient undergoing total knee arthroplasty is outlined. The specific objectives are strong quadriceps setting, straight leg raising, flexion of the knee to at least 90 degrees, and extension of the knee to 0 degrees. The program emphasizes the importance of early institution of exercises and early ambulation."}
{"id": "PMID:195295", "title": "Analysis of dream contents by scaled and rated measurements.", "content": "The study was undertaken in order to test a dream-rating scale and to propose some modifications, especially for use in laboratory situations where the effect of a given experimental factor is to be assessed on mental activity in sleep. Dreams collected from normal subjects under EEG monitoring were analysed in detail in order to establish definitions for each rating point of each dimension of the rating scale. The scoring of a second set of dreams by two judges using this scale resulted in an inter-rater agreement significantly above the level of chance agreement.", "contents": "Analysis of dream contents by scaled and rated measurements. The study was undertaken in order to test a dream-rating scale and to propose some modifications, especially for use in laboratory situations where the effect of a given experimental factor is to be assessed on mental activity in sleep. Dreams collected from normal subjects under EEG monitoring were analysed in detail in order to establish definitions for each rating point of each dimension of the rating scale. The scoring of a second set of dreams by two judges using this scale resulted in an inter-rater agreement significantly above the level of chance agreement."}
{"id": "PMID:195302", "title": "Distribution of lung metastases in the axial plane. A combined radiological-pathological study.", "content": "The appearance of lung metastases and their distribution in the axial plane was studied on radiographs of formalin-vapour inflated fixed lungs. The results show that the vast majority of lung metastases are to be found at the periphery of the lung, irrespective of cavitation or of their shape or size. This distribution cannot be explained by hydro-dynamic factors, but may be related to the susceptibility of metastases in different parts of the lung. the metastases were also analysed as to their appearances, namely well-defined nodular, star-like, ill-defined edge and cavitating. No definite correlation with distribution was apparent but when extremely numerous, metastases were usually less than 1 cm in diameter with ill-defined margins. This could be due to their rapidity of growth.", "contents": "Distribution of lung metastases in the axial plane. A combined radiological-pathological study. The appearance of lung metastases and their distribution in the axial plane was studied on radiographs of formalin-vapour inflated fixed lungs. The results show that the vast majority of lung metastases are to be found at the periphery of the lung, irrespective of cavitation or of their shape or size. This distribution cannot be explained by hydro-dynamic factors, but may be related to the susceptibility of metastases in different parts of the lung. the metastases were also analysed as to their appearances, namely well-defined nodular, star-like, ill-defined edge and cavitating. No definite correlation with distribution was apparent but when extremely numerous, metastases were usually less than 1 cm in diameter with ill-defined margins. This could be due to their rapidity of growth."}
{"id": "PMID:195303", "title": "Angiography in the diagnosis of retroperitoneal and mediastinal chemodectomas. Report of two cases.", "content": "Two cases of angiographically demonstrated chemodectomas of uncommon locations and behavior are reported: one located retroperitoneally and one with multi-centric sites including both carotid bodies and the upper mediastinum, with late distant bone metastases. Based on this experience and that reported by others, the angiographic appearance of chemodectomas is described and the value of angiography in the diagnosis and therapy of chemodectomas is discussed.", "contents": "Angiography in the diagnosis of retroperitoneal and mediastinal chemodectomas. Report of two cases. Two cases of angiographically demonstrated chemodectomas of uncommon locations and behavior are reported: one located retroperitoneally and one with multi-centric sites including both carotid bodies and the upper mediastinum, with late distant bone metastases. Based on this experience and that reported by others, the angiographic appearance of chemodectomas is described and the value of angiography in the diagnosis and therapy of chemodectomas is discussed."}
{"id": "PMID:195304", "title": "[Differential diagnosis of microcalcifications, X-ray film analysis of 60 intraductal carcinoma, the triangle principle (author's transl)].", "content": "Roentgenological criteria of microcalcification in intraductal carcinoma were examined in 60 cases and verified by the \"double-blind test\". The triad polymorphy, dense colonization, triangle principle has proved to be of useful for the differential diagnosis.", "contents": "[Differential diagnosis of microcalcifications, X-ray film analysis of 60 intraductal carcinoma, the triangle principle (author's transl)]. Roentgenological criteria of microcalcification in intraductal carcinoma were examined in 60 cases and verified by the \"double-blind test\". The triad polymorphy, dense colonization, triangle principle has proved to be of useful for the differential diagnosis."}
{"id": "PMID:195305", "title": "Computed tomography of abdominal mass lesions in children. Initial experience.", "content": "Use of a Delta scanner has resulted in delineation of neoplastic, obstructive and inflammatory renal diseases, hepatic tumors, and other abdominopelvic mass lesions. Of 47 patients examined, 32 had proved mass lesions. Computed tomography provided unique information about the complete delineation and nature of lesions and detected unrecognized lesions. Technical problems and solutions are discussed.", "contents": "Computed tomography of abdominal mass lesions in children. Initial experience. Use of a Delta scanner has resulted in delineation of neoplastic, obstructive and inflammatory renal diseases, hepatic tumors, and other abdominopelvic mass lesions. Of 47 patients examined, 32 had proved mass lesions. Computed tomography provided unique information about the complete delineation and nature of lesions and detected unrecognized lesions. Technical problems and solutions are discussed."}
{"id": "PMID:195306", "title": "Correlation of computed tomography, gray scale ultrasonography, and radionuclide imaging of the liver in detecting space-occupying processes.", "content": "The abilities of computed tomography (CT; scanning time=2.7 min), gray scale ultrasonography, and radionuclide imaging to detect and characterize space-occupying processes in the liver were compared. A numerical rating scale which emphasized detection abilities resulted in ultrasonography scoring 3.5 CT 3.2, and radionuclide imaging 2.9. CT resulted in no false positives and 6 false negatives, caused mainly by motion artifacts. The simplest technique, radionuclide imaging, also had the smallest number (2) of false negatives; it is therefore recommended as the screening procedure of choice. Sonography or CT should be done for those patients with a prior suspicious finding.", "contents": "Correlation of computed tomography, gray scale ultrasonography, and radionuclide imaging of the liver in detecting space-occupying processes. The abilities of computed tomography (CT; scanning time=2.7 min), gray scale ultrasonography, and radionuclide imaging to detect and characterize space-occupying processes in the liver were compared. A numerical rating scale which emphasized detection abilities resulted in ultrasonography scoring 3.5 CT 3.2, and radionuclide imaging 2.9. CT resulted in no false positives and 6 false negatives, caused mainly by motion artifacts. The simplest technique, radionuclide imaging, also had the smallest number (2) of false negatives; it is therefore recommended as the screening procedure of choice. Sonography or CT should be done for those patients with a prior suspicious finding."}
{"id": "PMID:195307", "title": "Improved myocardial infarct localization by combination of scintigraphy and ventricular wall motion evaluation.", "content": "Localization of acute myocardial infarcts can be done directly by imaging 99mTc pyrophosphate in the infarcted myocardium, or indirectly by analysis of wall motion abnormalities. Combining these modalities improves the sensitivity and specificity of the study. Forth-nine consecutive abnormal studies were analyzed in which both wall motion and static images were obtained with a single injection of pyrophosphate. At least 50% of the acute infarcts were better localized (or additional information obtained) by combining the modalities.", "contents": "Improved myocardial infarct localization by combination of scintigraphy and ventricular wall motion evaluation. Localization of acute myocardial infarcts can be done directly by imaging 99mTc pyrophosphate in the infarcted myocardium, or indirectly by analysis of wall motion abnormalities. Combining these modalities improves the sensitivity and specificity of the study. Forth-nine consecutive abnormal studies were analyzed in which both wall motion and static images were obtained with a single injection of pyrophosphate. At least 50% of the acute infarcts were better localized (or additional information obtained) by combining the modalities."}
{"id": "PMID:195308", "title": "A critical review of the efficacy of 99mTc pyrophosphate in detecting myocardial infarction in 103 patients.", "content": "Patients imaged with 99mTc pyrophosphate for myocardial infarction between October 1975 and March 1976 were reviewed. There were 103 patients and 114 images obtained. The clinical criteria of either or electrocardiographic changes were used to validate a myocardial infarct. We experienced 92.4% true negatives, 68.7% true positives, 7.5% false positives and 31.3% false negatives. It technically compromised scans were exclude (those with blood-pool activity, overlying costal cartilage), the false-negative rate was 15.4%. These data show that the presence of a negative phosphate scan does not rule out the possibility of a recent small, less than 2.5-cm subendocardial myocardial infarction.", "contents": "A critical review of the efficacy of 99mTc pyrophosphate in detecting myocardial infarction in 103 patients. Patients imaged with 99mTc pyrophosphate for myocardial infarction between October 1975 and March 1976 were reviewed. There were 103 patients and 114 images obtained. The clinical criteria of either or electrocardiographic changes were used to validate a myocardial infarct. We experienced 92.4% true negatives, 68.7% true positives, 7.5% false positives and 31.3% false negatives. It technically compromised scans were exclude (those with blood-pool activity, overlying costal cartilage), the false-negative rate was 15.4%. These data show that the presence of a negative phosphate scan does not rule out the possibility of a recent small, less than 2.5-cm subendocardial myocardial infarction."}
{"id": "PMID:195309", "title": "The efficacy of thallium 201, 99mTc phosphates, and 99mTc MAA in localizing small myocardial infarctions in the pig.", "content": "An intercomparison was made of technetium phosphates, thallium 201, and technetium-labeled MAA to define areas of small myocardial infarction in pigs. Byinstilling 0.01 ml of mercury into the coronary arteries, 2-cm infarcts were created. Several of the infarcts were in the anterior left ventricular wall. None of the infarcts was imaged with 99mTc phosphates. Three of the seven thallium 201 images demonstrated only diffuse right ventricular activity. Three of the seven infarcts were imaged with technetium MAA; a perfusion defect was seen in the area of infarction. Technetium MAA is the most sensitive agent in defining areas of abnormal myocardial perfusion.", "contents": "The efficacy of thallium 201, 99mTc phosphates, and 99mTc MAA in localizing small myocardial infarctions in the pig. An intercomparison was made of technetium phosphates, thallium 201, and technetium-labeled MAA to define areas of small myocardial infarction in pigs. Byinstilling 0.01 ml of mercury into the coronary arteries, 2-cm infarcts were created. Several of the infarcts were in the anterior left ventricular wall. None of the infarcts was imaged with 99mTc phosphates. Three of the seven thallium 201 images demonstrated only diffuse right ventricular activity. Three of the seven infarcts were imaged with technetium MAA; a perfusion defect was seen in the area of infarction. Technetium MAA is the most sensitive agent in defining areas of abnormal myocardial perfusion."}
{"id": "PMID:195310", "title": "The radiological investigation of hepatic tumors in childhood.", "content": "In hepatic tumors seen in children, treatment and prognosis differ from tumor to tumor and thus accurate determination of their extent and characteristics is important. Evaluation by gray scale ultrasonography, radionuclide imaging and angiography has produced definable characteristics for the various tumor types and often allows distinction from other intrahepatic processes. In addition, chemotherapeutic treatment of initially unresectable malignant hepatic tumors can be followed by nuclear imaging, ultrasound and angiography to determine therapeutic response.", "contents": "The radiological investigation of hepatic tumors in childhood. In hepatic tumors seen in children, treatment and prognosis differ from tumor to tumor and thus accurate determination of their extent and characteristics is important. Evaluation by gray scale ultrasonography, radionuclide imaging and angiography has produced definable characteristics for the various tumor types and often allows distinction from other intrahepatic processes. In addition, chemotherapeutic treatment of initially unresectable malignant hepatic tumors can be followed by nuclear imaging, ultrasound and angiography to determine therapeutic response."}
{"id": "PMID:195316", "title": "Analogies and differences between reserpine PGO wave discharges and oculomotor phasic activity during paradoxical sleep in the cat.", "content": "In the present study the analogies and differences between phasic PGO activity of parodoxical sleep and the reserpine induced PGO waves were investigated. The oculomotor phasic activities in chronic cats were studied. It appeared that the intrinsic organisation of latencies and the appearance of phasic waves in the four structures studied were common to both experimental situations. However the sequential patterns of discharges were different in PS and under reserpine treatment.", "contents": "Analogies and differences between reserpine PGO wave discharges and oculomotor phasic activity during paradoxical sleep in the cat. In the present study the analogies and differences between phasic PGO activity of parodoxical sleep and the reserpine induced PGO waves were investigated. The oculomotor phasic activities in chronic cats were studied. It appeared that the intrinsic organisation of latencies and the appearance of phasic waves in the four structures studied were common to both experimental situations. However the sequential patterns of discharges were different in PS and under reserpine treatment."}
{"id": "PMID:195317", "title": "A structure-activity analysis of the preferred conformation of the benzyl substituent of tetrahydropapaveroline at the beta receptor.", "content": "The effect of restricting the motion of the 3,4-dihydroxybenzyl substituent of tetrahydropapaveroline (THI) on its ability to stimulate the beta adenylate cyclase of the rat erythrocyte was investigated. A number of protoberberines and aporphines were tested as models of two classes of compounds where the benzyl substituent is rigidly but differently fixed. Unexpectedly, the beta agonist activity was associated with both structural types. This could be explained by the assumption that a phenylalanyl or tyrosyl residue of the receptor protein is free to rotate and bind with either position of the benzyl moiety as fixed in the protoberberine and aporphine structures.", "contents": "A structure-activity analysis of the preferred conformation of the benzyl substituent of tetrahydropapaveroline at the beta receptor. The effect of restricting the motion of the 3,4-dihydroxybenzyl substituent of tetrahydropapaveroline (THI) on its ability to stimulate the beta adenylate cyclase of the rat erythrocyte was investigated. A number of protoberberines and aporphines were tested as models of two classes of compounds where the benzyl substituent is rigidly but differently fixed. Unexpectedly, the beta agonist activity was associated with both structural types. This could be explained by the assumption that a phenylalanyl or tyrosyl residue of the receptor protein is free to rotate and bind with either position of the benzyl moiety as fixed in the protoberberine and aporphine structures."}
{"id": "PMID:195318", "title": "Correlation of induced drug metabolism with titer of duck hepatitis virus in chickens.", "content": "While chickens infected with duck hepatitis virus showed no signs of clinical illness, their levels of hepatic cytochrome P-450 in response to phenobarbital induction and their microsomal aryl hydrocarbon hydroxylase activities in response to 3-methylcholanthrene induction were each found to correlate with the titer of virus recovered from the livers. These clear correlations indicate that avian hepatic drug metabolism is significantly modified during viral infection.", "contents": "Correlation of induced drug metabolism with titer of duck hepatitis virus in chickens. While chickens infected with duck hepatitis virus showed no signs of clinical illness, their levels of hepatic cytochrome P-450 in response to phenobarbital induction and their microsomal aryl hydrocarbon hydroxylase activities in response to 3-methylcholanthrene induction were each found to correlate with the titer of virus recovered from the livers. These clear correlations indicate that avian hepatic drug metabolism is significantly modified during viral infection."}
{"id": "PMID:195319", "title": "Cyclic nucleotides and prostaglandins (PGs) produced by the rabbit oviduct: effects of estrogen treatment.", "content": "Levels of cyclic AMP and cyclic GMP have been measured in oviducts of rabbits killed 68 hr after injection of human chorionic gonadotrophin (HCG) to induce ovulation. cAMP and cGMP levels were higher in the isthmus than in the ampulla. Estrogen treatment given at the same time as HCG increased cGMP levels. Levels of PGE and PGF in blood draining the oviduct were low and showed no effect of estrogen treatment at 68 hr after HCG.", "contents": "Cyclic nucleotides and prostaglandins (PGs) produced by the rabbit oviduct: effects of estrogen treatment. Levels of cyclic AMP and cyclic GMP have been measured in oviducts of rabbits killed 68 hr after injection of human chorionic gonadotrophin (HCG) to induce ovulation. cAMP and cGMP levels were higher in the isthmus than in the ampulla. Estrogen treatment given at the same time as HCG increased cGMP levels. Levels of PGE and PGF in blood draining the oviduct were low and showed no effect of estrogen treatment at 68 hr after HCG."}
{"id": "PMID:195320", "title": "The role of bursa-dependent responses in immunity to infectious laryngotracheitis.", "content": "The effect of combined day-old surgical bursectomy and cyclophosphamide therapy on the response of young chicks to Brucella abortus antigen and cloacal vaccination against infectious laryngotracheitis virus (ILTV) was examined. The combined treatment effectively prevented the development of serum antibody to both B abortus and ILTV, yet when these chickens were challenged with virulent ILTV, they were found to be immune. It is suggested that immunity to ILTV may depend on the development of a cell mediated immune response.", "contents": "The role of bursa-dependent responses in immunity to infectious laryngotracheitis. The effect of combined day-old surgical bursectomy and cyclophosphamide therapy on the response of young chicks to Brucella abortus antigen and cloacal vaccination against infectious laryngotracheitis virus (ILTV) was examined. The combined treatment effectively prevented the development of serum antibody to both B abortus and ILTV, yet when these chickens were challenged with virulent ILTV, they were found to be immune. It is suggested that immunity to ILTV may depend on the development of a cell mediated immune response."}
{"id": "PMID:195322", "title": "Vagal control of diaphragm timing in cat while breathing at elevated lung volumes.", "content": "This paper proposes and tests an hypothesis to account for the roles of the volume and rate components of vagal feedback in determining the steady-state pattern of breathing during continuous positive pressure breathing (PPB) and expiratory threshold loading (ETL) in Dial anesthetized cats. During PPB the duration of diaphragm activity (Tdi) is shortened; the duration of its expiratory pause (Tep) is lengthened with little or no change in cycle duration (Tt); with onset of inspiration, flow (dV/dt) is increased; as inspiration proceeds, flow decelerates (d2V/dt2). During ETL Tdi, Tep and Tt are all prolonged; dV/dt is decreased at onset of inspiration, with either no change or an acceleration in flow as inspiration proceeds. PPB and ETL cause similar increases in resting lung volume and Tep, and high negative correlations between Tdi and flow. These relationship suggest that the 'volume component' of vagal feedback is one important factor controlling Tep whereas the 'rate component' contributes to the restraint of Tdi.", "contents": "Vagal control of diaphragm timing in cat while breathing at elevated lung volumes. This paper proposes and tests an hypothesis to account for the roles of the volume and rate components of vagal feedback in determining the steady-state pattern of breathing during continuous positive pressure breathing (PPB) and expiratory threshold loading (ETL) in Dial anesthetized cats. During PPB the duration of diaphragm activity (Tdi) is shortened; the duration of its expiratory pause (Tep) is lengthened with little or no change in cycle duration (Tt); with onset of inspiration, flow (dV/dt) is increased; as inspiration proceeds, flow decelerates (d2V/dt2). During ETL Tdi, Tep and Tt are all prolonged; dV/dt is decreased at onset of inspiration, with either no change or an acceleration in flow as inspiration proceeds. PPB and ETL cause similar increases in resting lung volume and Tep, and high negative correlations between Tdi and flow. These relationship suggest that the 'volume component' of vagal feedback is one important factor controlling Tep whereas the 'rate component' contributes to the restraint of Tdi."}
{"id": "PMID:195323", "title": "[261 cases of bronchopulmonary cancer detected by radiophotography].", "content": "In Bucharest, district 6, of the 1 151 313 radiophotographies performed, 261 revealed bronchopulmonary cancers (22.6 per 10 000) of which 73% males and 27% females, the 50--70 years age group being the most affected (181 cases, i.e. 70%). The 85% deaths occurred within 2 years after detection. In 68% (177 cases) cancer was peripheral and in 32% centrohillar. The peripheral localization in 68% of the cases opens prospects for an early detection by dynamic follow up of the pulmonary radiophotography at shorter intervals, especially in the age group with a higher cancer risk (50--70 years), indicating in some cases immediate admission to a surgical department.", "contents": "[261 cases of bronchopulmonary cancer detected by radiophotography]. In Bucharest, district 6, of the 1 151 313 radiophotographies performed, 261 revealed bronchopulmonary cancers (22.6 per 10 000) of which 73% males and 27% females, the 50--70 years age group being the most affected (181 cases, i.e. 70%). The 85% deaths occurred within 2 years after detection. In 68% (177 cases) cancer was peripheral and in 32% centrohillar. The peripheral localization in 68% of the cases opens prospects for an early detection by dynamic follow up of the pulmonary radiophotography at shorter intervals, especially in the age group with a higher cancer risk (50--70 years), indicating in some cases immediate admission to a surgical department."}
{"id": "PMID:195324", "title": "[Possibilities of cobalt therapy in bronchopulmonary cancer].", "content": "Cobaltotherapy was applied in 194 cases of bronchopulmonary cancer in the Oncologic Institute of Cluj-Napoca, during the 1967--1974 period. The mean survial was of 15 months, the results being influenced by the histologic type and locoregional extent apraised on the basis of the TNM classification proposed by the American Joint Committe for Cancer Staging and End Result Reporting. The mean survival after irradiation was of 9.7% and 5.1% at 3 and 5 years respectively. Standardization of the cases according to the TNM criteria showed the advanced stage of the patients referred for radiotherapy, proving a useful tool for establishing the prognosis and therapeutical indications. Next to the histological type and TNM category, the efficiency of radiotherapy is also influenced by the size and shape of the tumor, which conditions the irradiation technique. The central tumours or those of the upper lobes may be irradiated by small 150 cm2 beams and are the only ones that benefit by radical radiotherapy, the survival rate at 2 and 5 years being 12.3% and 7.6% respectively. In all the other cases the prognosis is more reserved, suggesting the necessity of associating chemotherapy or immunotherapy for improving the results.", "contents": "[Possibilities of cobalt therapy in bronchopulmonary cancer]. Cobaltotherapy was applied in 194 cases of bronchopulmonary cancer in the Oncologic Institute of Cluj-Napoca, during the 1967--1974 period. The mean survial was of 15 months, the results being influenced by the histologic type and locoregional extent apraised on the basis of the TNM classification proposed by the American Joint Committe for Cancer Staging and End Result Reporting. The mean survival after irradiation was of 9.7% and 5.1% at 3 and 5 years respectively. Standardization of the cases according to the TNM criteria showed the advanced stage of the patients referred for radiotherapy, proving a useful tool for establishing the prognosis and therapeutical indications. Next to the histological type and TNM category, the efficiency of radiotherapy is also influenced by the size and shape of the tumor, which conditions the irradiation technique. The central tumours or those of the upper lobes may be irradiated by small 150 cm2 beams and are the only ones that benefit by radical radiotherapy, the survival rate at 2 and 5 years being 12.3% and 7.6% respectively. In all the other cases the prognosis is more reserved, suggesting the necessity of associating chemotherapy or immunotherapy for improving the results."}
{"id": "PMID:195325", "title": "[Emergency pneumonectomy for severe hemoptysis in pulmonary tuberculosis].", "content": "The authors present two cases of severe tuberculous hemopthysis cured by pneumectomy. The patients had repeatedly presented severe hemopthysis meanacing their life and necessitated intensive resbuscitation, with intubation and mechanical respiratory prostheses. The authors also discuss the mechanism of death in severe hemopthysis, demonstrating that death is especially due to bronchial obstruction by clots of blood.", "contents": "[Emergency pneumonectomy for severe hemoptysis in pulmonary tuberculosis]. The authors present two cases of severe tuberculous hemopthysis cured by pneumectomy. The patients had repeatedly presented severe hemopthysis meanacing their life and necessitated intensive resbuscitation, with intubation and mechanical respiratory prostheses. The authors also discuss the mechanism of death in severe hemopthysis, demonstrating that death is especially due to bronchial obstruction by clots of blood."}
{"id": "PMID:195329", "title": "[Non-culturable Koch bacilli during antitubercular chemotherapy].", "content": "The authors have performed 58435 microscopic examinations, of which 3813 were positive, and found 209 (5,48%) cases of non-cultivable Koch bacilli. The major bacteriological, clinico-evolutive and therapeutical aspects are examined. Most of the cases showing a syndrome of positive homogenate with a negative culture were rather recent ones (an evolution of less than 2 years in 73,68% of the total) and the highest frequency was found in those in which the treatment was in its first year. No direct relationship could be demonstrated between the number of germs (the Gaffky scale) and the frequency of the syndrome. The factors influencing the occurrence and the development of the syndrome are: the structure of the lesions, the method of bacteriologic examination, the therapy applied, and a certain immunologic reactivity. According to the authors the significance of this syndrome is positive in most of the cases, indicating a regression that has not been completed. The most reasonable attitude is a differentiated one, depending on each case, integrating the data obtained by the bacteriological examination in the therapeutic and evolutive clinico-radiologic context.", "contents": "[Non-culturable Koch bacilli during antitubercular chemotherapy]. The authors have performed 58435 microscopic examinations, of which 3813 were positive, and found 209 (5,48%) cases of non-cultivable Koch bacilli. The major bacteriological, clinico-evolutive and therapeutical aspects are examined. Most of the cases showing a syndrome of positive homogenate with a negative culture were rather recent ones (an evolution of less than 2 years in 73,68% of the total) and the highest frequency was found in those in which the treatment was in its first year. No direct relationship could be demonstrated between the number of germs (the Gaffky scale) and the frequency of the syndrome. The factors influencing the occurrence and the development of the syndrome are: the structure of the lesions, the method of bacteriologic examination, the therapy applied, and a certain immunologic reactivity. According to the authors the significance of this syndrome is positive in most of the cases, indicating a regression that has not been completed. The most reasonable attitude is a differentiated one, depending on each case, integrating the data obtained by the bacteriological examination in the therapeutic and evolutive clinico-radiologic context."}
{"id": "PMID:195330", "title": "[Aspects of pulmonary function in states of hyperhydration].", "content": "The authors have investigated in 10 young and healthy men the changes occurring in the cardio-respiratory apparatus following the perfusion with non-colloid isotonie volemic solutions. Exploration of volumetry and of pulmonary mechanics have been performed, hemodynamic tests and pulmonary angiograms. The results indicate the development of slight interstitial oedema, without intra-alveolar transsudation or obstructive phenomena in the aerial pathways. The cardio-vascular apparatus shows satisfactory adaptability through central and peripheral mechanisms in conditions of hyperhydration.", "contents": "[Aspects of pulmonary function in states of hyperhydration]. The authors have investigated in 10 young and healthy men the changes occurring in the cardio-respiratory apparatus following the perfusion with non-colloid isotonie volemic solutions. Exploration of volumetry and of pulmonary mechanics have been performed, hemodynamic tests and pulmonary angiograms. The results indicate the development of slight interstitial oedema, without intra-alveolar transsudation or obstructive phenomena in the aerial pathways. The cardio-vascular apparatus shows satisfactory adaptability through central and peripheral mechanisms in conditions of hyperhydration."}
{"id": "PMID:195331", "title": "[An experimental study of autotopagnosia (author's transl)].", "content": "One hundred and twenty patients with unilateral cerebral hemisphere damage (54 aphasics, 21 non-aphasic left and 45 right brain-damaged patients and 57 control subjects without cerebral lesions were given a battery of verbal and non-verbal tests of autotopagnosia, with the aim of studying the relationships between disorders of body schema and the side of the hemispheric lesion. A second aspect of our research consisted in understanding whether impairment in naming and pointing to body parts following verbal commands was really a specific symptom or if the same difficulty was found when patients were asked to name or to point to parts of objects other than the human body. Our results have shown that: 1) the aphasic patients are significantly more impaired than the non-aphasic patients on all the tests, non-verbal as well as verbal; 2) when results obtained on tests of naming and of pointing to parts of the human body were matched with results obtained on tests of naming and of pointing to parts of objects other than the human body, no difference could be demonstrated. These findings suggest that autotopagnosia is a nonspecific symptom, and that it does not find a satisfactory explanation in terms of \"disorders of the body schema\".", "contents": "[An experimental study of autotopagnosia (author's transl)]. One hundred and twenty patients with unilateral cerebral hemisphere damage (54 aphasics, 21 non-aphasic left and 45 right brain-damaged patients and 57 control subjects without cerebral lesions were given a battery of verbal and non-verbal tests of autotopagnosia, with the aim of studying the relationships between disorders of body schema and the side of the hemispheric lesion. A second aspect of our research consisted in understanding whether impairment in naming and pointing to body parts following verbal commands was really a specific symptom or if the same difficulty was found when patients were asked to name or to point to parts of objects other than the human body. Our results have shown that: 1) the aphasic patients are significantly more impaired than the non-aphasic patients on all the tests, non-verbal as well as verbal; 2) when results obtained on tests of naming and of pointing to parts of the human body were matched with results obtained on tests of naming and of pointing to parts of objects other than the human body, no difference could be demonstrated. These findings suggest that autotopagnosia is a nonspecific symptom, and that it does not find a satisfactory explanation in terms of \"disorders of the body schema\"."}
{"id": "PMID:195335", "title": "[Inappropriate secretion of ACTH in cases of bronchial carcinoma].", "content": "In the light of seven cases of adrenal hypercorticalism associated with tumoral secretion of ACTH, the syndrome of inappropriate ACTH secretion is reviewed. This entity, which is related primarily to anaplastic bronchial carcinoma is characterized by paucity of clinical signs of hypercorticalism, rapidity of evolution and typical biological modifications. Other important criteria are hypokalemic alkalosis, high plasma levels of ACTH and 17-OHCS and failure of dexamethasome to suppress endogenous steroid secretion. However, the diagnosis can be proven only by extraction of a significant quantity of tumoral ACTH.", "contents": "[Inappropriate secretion of ACTH in cases of bronchial carcinoma]. In the light of seven cases of adrenal hypercorticalism associated with tumoral secretion of ACTH, the syndrome of inappropriate ACTH secretion is reviewed. This entity, which is related primarily to anaplastic bronchial carcinoma is characterized by paucity of clinical signs of hypercorticalism, rapidity of evolution and typical biological modifications. Other important criteria are hypokalemic alkalosis, high plasma levels of ACTH and 17-OHCS and failure of dexamethasome to suppress endogenous steroid secretion. However, the diagnosis can be proven only by extraction of a significant quantity of tumoral ACTH."}
{"id": "PMID:195336", "title": "Efflux of cyclic nucleotides from rat pineal: release of guanosine 3',5'-monophosphate from sympathetic nerve endings.", "content": "Potassium and norepinephrine stimulate the efflux of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) from intact pineal glands. The postsynaptic beta-adrenergic receptor mediates the efflux of cyclic AMP. In contrast, the efflux of cyclic GMP requires calcium and intact nerve endings. It appears that sympathetic nerve endings may release cyclic GMP into the synaptic space.", "contents": "Efflux of cyclic nucleotides from rat pineal: release of guanosine 3',5'-monophosphate from sympathetic nerve endings. Potassium and norepinephrine stimulate the efflux of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) from intact pineal glands. The postsynaptic beta-adrenergic receptor mediates the efflux of cyclic AMP. In contrast, the efflux of cyclic GMP requires calcium and intact nerve endings. It appears that sympathetic nerve endings may release cyclic GMP into the synaptic space."}
{"id": "PMID:195337", "title": "Dibutyryl cyclic AMP mimics ovariectomy: nuclear protein phosphorylation in mammary tumor regression.", "content": "Growth of mammary carcinoma induced by 7,12-dimethyl-benz(a) anthracene is arrested by either ovariectomy or treatment with N6,O2-dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP). When this occurs, a new nonhistone protein species becomes the predominant endogenous substrate of cyclic AMP-dependent protein kinase in the tumor nuclei. Phosphorylation of this regression-associated protein ceases when resumption of tumor growth is induced by either the injection of 17 beta-estradiol or cessation of dibutyryl cyclic AMP treatment. Thus phosphorylation of regression-associated protein may play a role in the regression of hormone-dependent mammary tumors.", "contents": "Dibutyryl cyclic AMP mimics ovariectomy: nuclear protein phosphorylation in mammary tumor regression. Growth of mammary carcinoma induced by 7,12-dimethyl-benz(a) anthracene is arrested by either ovariectomy or treatment with N6,O2-dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP). When this occurs, a new nonhistone protein species becomes the predominant endogenous substrate of cyclic AMP-dependent protein kinase in the tumor nuclei. Phosphorylation of this regression-associated protein ceases when resumption of tumor growth is induced by either the injection of 17 beta-estradiol or cessation of dibutyryl cyclic AMP treatment. Thus phosphorylation of regression-associated protein may play a role in the regression of hormone-dependent mammary tumors."}
{"id": "PMID:195338", "title": "Modulation of macrophage tumoricidal capability by components of normal serum: a central role for lipid.", "content": "The tumoricidal capabilities of macrophages can be reversibly inhibited by a lipoprotein of high molecular weight, and the inhibition appears to be reproduced by enrichment of macrophage plasma membranes with cholesterol. A second serum component of lower molecular weight enhances macrophage cytotoxicity. The presence of these components in normal serums suggests a physiological role for such factors in the regulation of macrophage function.", "contents": "Modulation of macrophage tumoricidal capability by components of normal serum: a central role for lipid. The tumoricidal capabilities of macrophages can be reversibly inhibited by a lipoprotein of high molecular weight, and the inhibition appears to be reproduced by enrichment of macrophage plasma membranes with cholesterol. A second serum component of lower molecular weight enhances macrophage cytotoxicity. The presence of these components in normal serums suggests a physiological role for such factors in the regulation of macrophage function."}
{"id": "PMID:195339", "title": "Antigenic shift of visna virus in persistently infected sheep.", "content": "Visna viruses isolated from persistently infected sheep were antigenically distinct from the plaque-purified virus used for inoculation. The selection of antigenic variants under antibody pressure, thought to occur in vivo, was reproduced in sheep cell cultures inoculated with plaque-purified visna virus and maintained in antibody. Antigenic shift may be a mechanism for persistence of virus in slow or recurrent viral infections.", "contents": "Antigenic shift of visna virus in persistently infected sheep. Visna viruses isolated from persistently infected sheep were antigenically distinct from the plaque-purified virus used for inoculation. The selection of antigenic variants under antibody pressure, thought to occur in vivo, was reproduced in sheep cell cultures inoculated with plaque-purified visna virus and maintained in antibody. Antigenic shift may be a mechanism for persistence of virus in slow or recurrent viral infections."}
{"id": "PMID:195341", "title": "Human chorionic gonadotropin-like substance in nonendocrine tissues of normal subjects.", "content": "By means of two assay systems, a beta chain human chorionic gonadotropin radioimmunoassay and a radioreceptor gonadotropin assay, a chorionic gonadotropin-like substance was demonstrated in extracts of liver and colon obtained at autopsy from three patients who died of nonneoplastic disease. In contrast to placental chorionic gonadotropin, colon and liver chorionic gonadotropin was not bound to concanavalin A-Sepharose columns, indicating that this substance possessed little or no carbohydrate. Previous workers demonstrated that desialylated human chorionic gonadotropin possesses little or no bioactivity in vivo but retains full radioreceptor and radioimmunoassay activity in vitro. Our data suggest that the genome responsible for the human chorionic gonadotropin production is not completely suppressed in adult nonendocrine tissues, and that the chorionic gonadotropin produced by colon and liver has little or no bioactivity in vivo because of its low carbohydrate content. Since many normal tissues produce chorionic gonadotropin, bioactivity may be modulated by regulation of carbohydrate content.", "contents": "Human chorionic gonadotropin-like substance in nonendocrine tissues of normal subjects. By means of two assay systems, a beta chain human chorionic gonadotropin radioimmunoassay and a radioreceptor gonadotropin assay, a chorionic gonadotropin-like substance was demonstrated in extracts of liver and colon obtained at autopsy from three patients who died of nonneoplastic disease. In contrast to placental chorionic gonadotropin, colon and liver chorionic gonadotropin was not bound to concanavalin A-Sepharose columns, indicating that this substance possessed little or no carbohydrate. Previous workers demonstrated that desialylated human chorionic gonadotropin possesses little or no bioactivity in vivo but retains full radioreceptor and radioimmunoassay activity in vitro. Our data suggest that the genome responsible for the human chorionic gonadotropin production is not completely suppressed in adult nonendocrine tissues, and that the chorionic gonadotropin produced by colon and liver has little or no bioactivity in vivo because of its low carbohydrate content. Since many normal tissues produce chorionic gonadotropin, bioactivity may be modulated by regulation of carbohydrate content."}
{"id": "PMID:195342", "title": "Three hypolipidemic drugs increase hepatic palmitoyl-coenzyme A oxidation in the rat.", "content": "Male rats treated with clofibrate, tibric acid, or Wy-14,643 show an 11- to 18-fold increase in the capacity of their livers to oxidize palmitoyl-coenzyme A. This provides a plausible biochemical mechanism for the action of these hypolipidemic drugs in reducing lipid concentrations in the serum.", "contents": "Three hypolipidemic drugs increase hepatic palmitoyl-coenzyme A oxidation in the rat. Male rats treated with clofibrate, tibric acid, or Wy-14,643 show an 11- to 18-fold increase in the capacity of their livers to oxidize palmitoyl-coenzyme A. This provides a plausible biochemical mechanism for the action of these hypolipidemic drugs in reducing lipid concentrations in the serum."}
{"id": "PMID:195343", "title": "1,25-dihydroxycholecalciferol and parathormone: effects on isolated osteoclast-like and osteoblast-like cells.", "content": "The actions of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and parathormone, both effective bone-resorptive agents in vivo and in vitro, were tested on CT (osteoclast-like) and PT (osteoblast-like) bone cells maintained in culture. Both agents stimulated acid phosphatase activity and hyaluronate synthesis in the CT cells and decreased alkaline phosphatase, citrate decarboxylation, and collagen synthesis in the PT cells. Calcitonin inhibited the changes induced in the CT but not in the PT cells. The activity of 1,25-(OH)2D3 differed from that of parathormone in one key respect: it did not increase cellular cyclic adenosine monophosphate, whereas parathormone did. Prior incubation of the bone cells with 1,25-(OH)2D3 for 6 to 24 hours made the cells refractory to the effect of parathormone on cyclic adenosine monophosphate formation. These data suggest that 1,25-(OH)2D3 and parathormone induce bone resorption by affecting the same cell types (osteoblasts and osteoclasts) although at different cellular sites.", "contents": "1,25-dihydroxycholecalciferol and parathormone: effects on isolated osteoclast-like and osteoblast-like cells. The actions of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and parathormone, both effective bone-resorptive agents in vivo and in vitro, were tested on CT (osteoclast-like) and PT (osteoblast-like) bone cells maintained in culture. Both agents stimulated acid phosphatase activity and hyaluronate synthesis in the CT cells and decreased alkaline phosphatase, citrate decarboxylation, and collagen synthesis in the PT cells. Calcitonin inhibited the changes induced in the CT but not in the PT cells. The activity of 1,25-(OH)2D3 differed from that of parathormone in one key respect: it did not increase cellular cyclic adenosine monophosphate, whereas parathormone did. Prior incubation of the bone cells with 1,25-(OH)2D3 for 6 to 24 hours made the cells refractory to the effect of parathormone on cyclic adenosine monophosphate formation. These data suggest that 1,25-(OH)2D3 and parathormone induce bone resorption by affecting the same cell types (osteoblasts and osteoclasts) although at different cellular sites."}
{"id": "PMID:195345", "title": "Rare occurrence of Addison's disease and diabetes mellitus in children.", "content": "We report on two children with both Addison's disease and diabetes mellitus, a rare occurrence in children. One of the children first developed Addison's disease and later developed diabetes mellitus, while the other had the onset of diabetes mellitus first and later Addison's disease. In the latter patient a direct relationship was shown between the insulin dose and adrenal cortical hormone. Organ-specific antibody studies are reported and the diagnosis and management of these combined endocrinopathies are discussed.", "contents": "Rare occurrence of Addison's disease and diabetes mellitus in children. We report on two children with both Addison's disease and diabetes mellitus, a rare occurrence in children. One of the children first developed Addison's disease and later developed diabetes mellitus, while the other had the onset of diabetes mellitus first and later Addison's disease. In the latter patient a direct relationship was shown between the insulin dose and adrenal cortical hormone. Organ-specific antibody studies are reported and the diagnosis and management of these combined endocrinopathies are discussed."}
{"id": "PMID:195346", "title": "Endodermal sinus tumor of the anterior mediastinum.", "content": "An endodermal sinus tumor presenting as a lobulated anterior mediastinal mass in a 20-year-old white man is reported. The clinical implications, histology, and origin of this rare germ cell tumor are discussed. The invasive nature of this highly malignant neoplasm prevented complete surgical resection.", "contents": "Endodermal sinus tumor of the anterior mediastinum. An endodermal sinus tumor presenting as a lobulated anterior mediastinal mass in a 20-year-old white man is reported. The clinical implications, histology, and origin of this rare germ cell tumor are discussed. The invasive nature of this highly malignant neoplasm prevented complete surgical resection."}
{"id": "PMID:195347", "title": "Small cell carcinoma of the lung presenting as bilateral hilar adenopathy.", "content": "A patient in whom a presumptive diagnosis of sarcoidosis was made on the basis of nonspecific symptoms and BHA on chest roentgenogram is described. At necropsy the BHA was found to be due to a metastatic small cell undifferentiated carcinoma of the lung. This tumor is a previously unrecognized cause of BHA.", "contents": "Small cell carcinoma of the lung presenting as bilateral hilar adenopathy. A patient in whom a presumptive diagnosis of sarcoidosis was made on the basis of nonspecific symptoms and BHA on chest roentgenogram is described. At necropsy the BHA was found to be due to a metastatic small cell undifferentiated carcinoma of the lung. This tumor is a previously unrecognized cause of BHA."}
{"id": "PMID:195348", "title": "Association of breast cancer with myeloproliferative disorders.", "content": "Three cases of myeloproliferative disorders in patients with breast cancer are described. The first patient developed acute myeloblastic leukemia 26 years after her initial breast cancer; the second patient developed chronic myelogenous leukemia three years after the diagnosis of breast cancer; the third patient had polycythemia vera for nine years before cancer of the breast was noted. The literature dealing with the association of cancer and myeloproliferative disorders is reviewed. Possible explanations for this association are considered.", "contents": "Association of breast cancer with myeloproliferative disorders. Three cases of myeloproliferative disorders in patients with breast cancer are described. The first patient developed acute myeloblastic leukemia 26 years after her initial breast cancer; the second patient developed chronic myelogenous leukemia three years after the diagnosis of breast cancer; the third patient had polycythemia vera for nine years before cancer of the breast was noted. The literature dealing with the association of cancer and myeloproliferative disorders is reviewed. Possible explanations for this association are considered."}
{"id": "PMID:195349", "title": "Pseudomonas endocarditis: cure with carbenicillin and polymyxin B.", "content": "A case of Pseudomonas endocarditis cured with carbenicillin and polymyxin B is described. Initially, this patient was considered a medical treatment failure when a full course of carbenicillin and gentamicin failed to effect a cure. The importance of monitoring therapy with appropriate laboratory tests is stressed.", "contents": "Pseudomonas endocarditis: cure with carbenicillin and polymyxin B. A case of Pseudomonas endocarditis cured with carbenicillin and polymyxin B is described. Initially, this patient was considered a medical treatment failure when a full course of carbenicillin and gentamicin failed to effect a cure. The importance of monitoring therapy with appropriate laboratory tests is stressed."}
{"id": "PMID:195352", "title": "Linkage relationship between the genes for thymidine kinase and galactokinase in different primates.", "content": "In this study we investigated the expression of primate galactokinase in somatic cell hybrids between a thymidine kinase-deficient mouse cell line and two different primate cell lines, one of which was derived from African green monkey kidney cells and the other from chimpanzee fibroblasts. All the African green monkey-mouse hybrid clones, selected in HAT medium, expressed monkey galactokinase activity and contained a monkey chromosome similar to a human E-group chromosome. When these clones were backselected in medium containing 5-bromodeoxyuridine, both this chromosome and the monkey galactokinase activity were lost. All the hybrid clones between mouse and chimpanzee cells, which were selected in HAT medium, contained the chimpanzee chromosome 17 and expressed chimpanzee galactokinase activity. These results indicate that the linkage relationship between galactokinase and thymidine kinase has been maintained in 3 divergent primate species--man, chimpanzee, and Old World monkey.", "contents": "Linkage relationship between the genes for thymidine kinase and galactokinase in different primates. In this study we investigated the expression of primate galactokinase in somatic cell hybrids between a thymidine kinase-deficient mouse cell line and two different primate cell lines, one of which was derived from African green monkey kidney cells and the other from chimpanzee fibroblasts. All the African green monkey-mouse hybrid clones, selected in HAT medium, expressed monkey galactokinase activity and contained a monkey chromosome similar to a human E-group chromosome. When these clones were backselected in medium containing 5-bromodeoxyuridine, both this chromosome and the monkey galactokinase activity were lost. All the hybrid clones between mouse and chimpanzee cells, which were selected in HAT medium, contained the chimpanzee chromosome 17 and expressed chimpanzee galactokinase activity. These results indicate that the linkage relationship between galactokinase and thymidine kinase has been maintained in 3 divergent primate species--man, chimpanzee, and Old World monkey."}
{"id": "PMID:195353", "title": "Chilling of somatic cells unnecessary for Sendai virus-induced heterokaryon formation.", "content": "Incubation of cell suspensions or monolayers at 4 degrees C for 20 min after addition of beta-propiolactone-inactivated Sendai virus did not enhance heterokaryon formation as compared to parallel cell cultures incubated at 37 degrees C immediately after the addition of Sendai virus. These findings show that the routine chilling of somatic cells in fusion experiments can be omitted.", "contents": "Chilling of somatic cells unnecessary for Sendai virus-induced heterokaryon formation. Incubation of cell suspensions or monolayers at 4 degrees C for 20 min after addition of beta-propiolactone-inactivated Sendai virus did not enhance heterokaryon formation as compared to parallel cell cultures incubated at 37 degrees C immediately after the addition of Sendai virus. These findings show that the routine chilling of somatic cells in fusion experiments can be omitted."}
{"id": "PMID:195354", "title": "Genetic homology between man and the chimpanzee: syntenic relationships of genes for galactokinase and thymidine kinase and adenovirus-12-induced gaps using chimpanzee-mouse somatic cell hybrids.", "content": "The induction by adenovirus-12 of a site-specific gap and assignment of the chimpanzee genes for thymidine kinase and galactokinase were studied by utilizing chimpanzee-mouse hybrid cells. It has been shown that adenovirus-12 induces a specific gap in the long arm of human chromosome 17 (HS 17); with chimpanzee-mouse hybrid cells the specific gap appears on the short arm of the chimpanzee homolog [PTR 19 (HS 17)] of HS 17. This result supports the proposed relationship of HS 17 to PTR 19 (HS 17) by means of a pericentric inversion. The chimpanzee thymidine kinase and galactokinase genes were assigned to PTR 19 (HS 17), further confirming the homology to HS 17. Other syntenic relationships and gene assignments were consistent with proposed homologies between chimpanzee and human chromosomes.", "contents": "Genetic homology between man and the chimpanzee: syntenic relationships of genes for galactokinase and thymidine kinase and adenovirus-12-induced gaps using chimpanzee-mouse somatic cell hybrids. The induction by adenovirus-12 of a site-specific gap and assignment of the chimpanzee genes for thymidine kinase and galactokinase were studied by utilizing chimpanzee-mouse hybrid cells. It has been shown that adenovirus-12 induces a specific gap in the long arm of human chromosome 17 (HS 17); with chimpanzee-mouse hybrid cells the specific gap appears on the short arm of the chimpanzee homolog [PTR 19 (HS 17)] of HS 17. This result supports the proposed relationship of HS 17 to PTR 19 (HS 17) by means of a pericentric inversion. The chimpanzee thymidine kinase and galactokinase genes were assigned to PTR 19 (HS 17), further confirming the homology to HS 17. Other syntenic relationships and gene assignments were consistent with proposed homologies between chimpanzee and human chromosomes."}
{"id": "PMID:195355", "title": "Drug-induced acute pancreatitis.", "content": "A review of the literature reflects numerous instances of acute pancreatitis developing in patients while being treated with drugs. The causative relation is not yet definitively established but, in several instances, there appears to be a probable relation. The literature records at least 112 patients with drug-induced acute pancreatitis. Fifty-one instances were caused by steroids or adrenocorticotropic hormone, six by estrogen, two by azathioprine, 16 by diurectics, two by hypercalcemia, 24 by chemotherapy, three by clonidine and phenformin, two by warfarin and one each by salicylate, 1-asparaginase and d-propoxyphene. In addition, many patients have experienced acute pancreatitis while receiving immunosuppressive therapy after renal transplantation.", "contents": "Drug-induced acute pancreatitis. A review of the literature reflects numerous instances of acute pancreatitis developing in patients while being treated with drugs. The causative relation is not yet definitively established but, in several instances, there appears to be a probable relation. The literature records at least 112 patients with drug-induced acute pancreatitis. Fifty-one instances were caused by steroids or adrenocorticotropic hormone, six by estrogen, two by azathioprine, 16 by diurectics, two by hypercalcemia, 24 by chemotherapy, three by clonidine and phenformin, two by warfarin and one each by salicylate, 1-asparaginase and d-propoxyphene. In addition, many patients have experienced acute pancreatitis while receiving immunosuppressive therapy after renal transplantation."}
{"id": "PMID:195356", "title": "Minilaparotomy as an aid to diagnosing liver disease.", "content": "A series of 168 patients who underwent minilaparotomy was analyzed. Twenty of these patients underwent omentoportography only and 148, open transhepatic cholangiogram. Diagnosis was obtained in 92 per cent of those undergoing evaluation of jaundice, and cholangiography was successful in 99 per cent of those with dilated ducts and in 91 per cent of the over-all group. tthe complications of the procedure have been infrequent and have included sepsis, wound infection and renal failure and, early in the series, bile leak and bleeding. The relative merits of this procedure compared with those percutaneous transhepatic cholangiography and endoscopic retrograde cholangiography were evaluated.", "contents": "Minilaparotomy as an aid to diagnosing liver disease. A series of 168 patients who underwent minilaparotomy was analyzed. Twenty of these patients underwent omentoportography only and 148, open transhepatic cholangiogram. Diagnosis was obtained in 92 per cent of those undergoing evaluation of jaundice, and cholangiography was successful in 99 per cent of those with dilated ducts and in 91 per cent of the over-all group. tthe complications of the procedure have been infrequent and have included sepsis, wound infection and renal failure and, early in the series, bile leak and bleeding. The relative merits of this procedure compared with those percutaneous transhepatic cholangiography and endoscopic retrograde cholangiography were evaluated."}
{"id": "PMID:195358", "title": "Autotransplantation of pancreatic islets without separation of exocrine and endocrine tissue in totally pancreatectomized dogs.", "content": "The aims of this study were to determine whether diabetes could be ameliorated in dogs by autotransplantation of pancreatic fragments to the spleen and to determine the optimal time of collagenase digestion for pancreatic tissue dispersal. Forty-eight dogs were made diabetic by total pancreatectomy. Fifteen dogs not further treated survived 7.0+/-1.1 (SE) days with a mean plasma glucose of 401+/-5 (SE) mg/100 ml 2 days after pancreatectomy. The pancreases of 33 dogs were distended with Hanks' solution, minced, digested with collagenase (600 microns/ml of tissue), for 0 to 25 minutes, and autotransplanted to the splenic pulp. The incidence of permanent normoglycemia (fasting plasma glucose less than 150 mg/100 ml) and the K value of glucose tolerance tests (GTT) performed 2 and 10 weeks after transplant were determined in experimental groups divided according to the length of collagenase digestion. All five dogs receiving undigested tissue remained hyperglycemic. One of seven dogs receiving tissue digested for 10 minutes became normoglycemic. In contrast, seven of eight, seven of seven, and six of six dogs receiving tissue digested for 15, 20, and 25 minutes, respectively, became normoglycemic (followed for 6 months). K values at 2 weeks were 1.20+/-1.19 (SE)% 1.60+/-0.25 (SE)%, and 0.78+/-0.08 (SE)% in the normolgycemic dogs of the 15, 20, and 25 minute digestion groups, respectively. The K value of normal dogs was 3.30+/-0.27 (SE)%. The glucose tolerance curves of the 20 minute group at 2 and 10 weeks most nearly approximated the curves of normal dogs. K values improved in all recipient dogs. Diabetes recurred immediately and death occurred at a mean of 4.8+/-1.5 days in 12 recipient dogs following splenectomy. We conclude that pancreatic fragments can be successfully autotransplanted to the spleen without separation of endocrine and exocrine tissue and that 20 minutes is the optimal period of collagenase digestion for tissue preparation.", "contents": "Autotransplantation of pancreatic islets without separation of exocrine and endocrine tissue in totally pancreatectomized dogs. The aims of this study were to determine whether diabetes could be ameliorated in dogs by autotransplantation of pancreatic fragments to the spleen and to determine the optimal time of collagenase digestion for pancreatic tissue dispersal. Forty-eight dogs were made diabetic by total pancreatectomy. Fifteen dogs not further treated survived 7.0+/-1.1 (SE) days with a mean plasma glucose of 401+/-5 (SE) mg/100 ml 2 days after pancreatectomy. The pancreases of 33 dogs were distended with Hanks' solution, minced, digested with collagenase (600 microns/ml of tissue), for 0 to 25 minutes, and autotransplanted to the splenic pulp. The incidence of permanent normoglycemia (fasting plasma glucose less than 150 mg/100 ml) and the K value of glucose tolerance tests (GTT) performed 2 and 10 weeks after transplant were determined in experimental groups divided according to the length of collagenase digestion. All five dogs receiving undigested tissue remained hyperglycemic. One of seven dogs receiving tissue digested for 10 minutes became normoglycemic. In contrast, seven of eight, seven of seven, and six of six dogs receiving tissue digested for 15, 20, and 25 minutes, respectively, became normoglycemic (followed for 6 months). K values at 2 weeks were 1.20+/-1.19 (SE)% 1.60+/-0.25 (SE)%, and 0.78+/-0.08 (SE)% in the normolgycemic dogs of the 15, 20, and 25 minute digestion groups, respectively. The K value of normal dogs was 3.30+/-0.27 (SE)%. The glucose tolerance curves of the 20 minute group at 2 and 10 weeks most nearly approximated the curves of normal dogs. K values improved in all recipient dogs. Diabetes recurred immediately and death occurred at a mean of 4.8+/-1.5 days in 12 recipient dogs following splenectomy. We conclude that pancreatic fragments can be successfully autotransplanted to the spleen without separation of endocrine and exocrine tissue and that 20 minutes is the optimal period of collagenase digestion for tissue preparation."}
{"id": "PMID:195359", "title": "End-to-side anastomosis of the mesenteric vein to the inferior vena cava in the treatment of glycogen storage disease: case report.", "content": "A 2-year-old boy with Type I glycogen storage disease received an end-to-side anastomosis of the mesenteric vein to the inferior vena cava with marked improvement in his biochemical factors and nutritional status and with shrinkage of the liver. The efficacy and simplicity of this technique and its lack of complications, as evidenced by follow-up studies over a 4 year period, suggest that its further use is warranted.", "contents": "End-to-side anastomosis of the mesenteric vein to the inferior vena cava in the treatment of glycogen storage disease: case report. A 2-year-old boy with Type I glycogen storage disease received an end-to-side anastomosis of the mesenteric vein to the inferior vena cava with marked improvement in his biochemical factors and nutritional status and with shrinkage of the liver. The efficacy and simplicity of this technique and its lack of complications, as evidenced by follow-up studies over a 4 year period, suggest that its further use is warranted."}
{"id": "PMID:195362", "title": "Binding of collagen by canine blood platelets.", "content": "The binding of 125I-collagen (tropocollagen) by canine blood platelets occurred in a concentration-dependent manner but no saturation effect could be observed. The binding of collagen was not entirely specific for platelets since various eucaryotic and procaryotic cells quantitatively bound collagen as well or better. The temporal response to added collagen appeared to be binding, 3H-serotonin release, and finally platelet aggregation. Non-polymerizing salt-soluble tropocollagen was bound as well as acid-soluble tropocollagen, however neither 3H-serotonin release nor platelet aggregation occurred. Furthermore, the binding activity was not destroyed by treatment with collagenase, galactose oxidase and glucose oxidase, nor by periodate oxidation. Platelet aggregation closely paralleled acid soluble collagen polymerization and both events were equally inhibited by arginine; however, arginine did not interfere with collagen binding. Scanning electron microscopy revealed an unusual morphological platelet response to collagen and platelets appeared to be nucleation sites for collagen polymerization.", "contents": "Binding of collagen by canine blood platelets. The binding of 125I-collagen (tropocollagen) by canine blood platelets occurred in a concentration-dependent manner but no saturation effect could be observed. The binding of collagen was not entirely specific for platelets since various eucaryotic and procaryotic cells quantitatively bound collagen as well or better. The temporal response to added collagen appeared to be binding, 3H-serotonin release, and finally platelet aggregation. Non-polymerizing salt-soluble tropocollagen was bound as well as acid-soluble tropocollagen, however neither 3H-serotonin release nor platelet aggregation occurred. Furthermore, the binding activity was not destroyed by treatment with collagenase, galactose oxidase and glucose oxidase, nor by periodate oxidation. Platelet aggregation closely paralleled acid soluble collagen polymerization and both events were equally inhibited by arginine; however, arginine did not interfere with collagen binding. Scanning electron microscopy revealed an unusual morphological platelet response to collagen and platelets appeared to be nucleation sites for collagen polymerization."}
{"id": "PMID:195363", "title": "Enhancement of platelet sensitivity to ADP-aggregation by isometric exercise in arteriosclerosis patients and its prevention.", "content": "A new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points: 1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment. 2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positve significant correlations between the values obtained by these three methods. 3. It was proved to be highly reproducible and is thought to be useful clinically. By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise.", "contents": "Enhancement of platelet sensitivity to ADP-aggregation by isometric exercise in arteriosclerosis patients and its prevention. A new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points: 1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment. 2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positve significant correlations between the values obtained by these three methods. 3. It was proved to be highly reproducible and is thought to be useful clinically. By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise."}
{"id": "PMID:195368", "title": "Radioactive nucleic acids-precursors: their potential value as tumor-localizing agents.", "content": "The distribution of 125I-uracil and 125I-deoxyuridine in tumor-bearing animals has been studied. 125I-deoxyuridine shows the characteristics of a tumor-scanning agent. The metabolic incorporation by tumors of this DNA-precursor indicates a potential value of this radiocompound for their detection, differentiation and follow-up of their evolution after therapy.", "contents": "Radioactive nucleic acids-precursors: their potential value as tumor-localizing agents. The distribution of 125I-uracil and 125I-deoxyuridine in tumor-bearing animals has been studied. 125I-deoxyuridine shows the characteristics of a tumor-scanning agent. The metabolic incorporation by tumors of this DNA-precursor indicates a potential value of this radiocompound for their detection, differentiation and follow-up of their evolution after therapy."}
{"id": "PMID:195370", "title": "Seroepidemiology of the poliovirus in Monrovia (Liberia).", "content": "Neutralizing antibodies against poliovirus have been studied in 265 persons in Monrovia (Liberia). 34% of the individuals studied possessed antibodies against the three polioviruses, 23% against two, 26% against one; the remaining 17% showed none. The three poliovirus antibodies were evenly distributed amongst the population, although there was an indication that antibodies to polio 2 occurred more commonly in females than in males. The distribution of the antibodies did not seem to be influenced by place of residence, source of drinking water or social class. Significant variations in the immunological state according to age were noted. The study of concordance and discordance of antibody titre in the blood of neonates and their mothers revealed that the lower percentage of titre concordance for polio 3 has no statistical value. The low titre in the neonates (an average for each poliovirus scarcely above 1:16) is a sign of insufficient titre in the adults. The need for a massive antipoliomyelitis campaign among infants and adult women is stressed.", "contents": "Seroepidemiology of the poliovirus in Monrovia (Liberia). Neutralizing antibodies against poliovirus have been studied in 265 persons in Monrovia (Liberia). 34% of the individuals studied possessed antibodies against the three polioviruses, 23% against two, 26% against one; the remaining 17% showed none. The three poliovirus antibodies were evenly distributed amongst the population, although there was an indication that antibodies to polio 2 occurred more commonly in females than in males. The distribution of the antibodies did not seem to be influenced by place of residence, source of drinking water or social class. Significant variations in the immunological state according to age were noted. The study of concordance and discordance of antibody titre in the blood of neonates and their mothers revealed that the lower percentage of titre concordance for polio 3 has no statistical value. The low titre in the neonates (an average for each poliovirus scarcely above 1:16) is a sign of insufficient titre in the adults. The need for a massive antipoliomyelitis campaign among infants and adult women is stressed."}
{"id": "PMID:195374", "title": "A method for producing hollow cone illumination electronically in the conventional transmission microscope.", "content": "An electronic device manipulates the primary beam in the conventional transmission microscope to produce a hollow cone of illumination with its apex located at the specimen. The device uses the existing tilt coils of the microscope, and modulates the D.C. signals to both x and y tilt directions simultaneously with various waveforms to produce Lissajous figures in the back-focal plane of the objective lens. Electron diffraction patterns can be recorded which reflect the manner in which the direct beam is tilted during exposure of a micrograph. In the bright-field imaging mode the device provides a microscope transfer function without zeros in all spatial directions and has been used to obtain high resolution images which are also free from the effect of chromatic aberration. A standard second condenser aperture is employed and the width of the cone annulus is readily controlled by defocusing the second condenser lens. The cone azimuthal angle is also controlled electronically; hence the device can also be used in the dark-field imaging mode. This device has been applied to imaging both amorphous and crystalline materials including biomolecular specimens.", "contents": "A method for producing hollow cone illumination electronically in the conventional transmission microscope. An electronic device manipulates the primary beam in the conventional transmission microscope to produce a hollow cone of illumination with its apex located at the specimen. The device uses the existing tilt coils of the microscope, and modulates the D.C. signals to both x and y tilt directions simultaneously with various waveforms to produce Lissajous figures in the back-focal plane of the objective lens. Electron diffraction patterns can be recorded which reflect the manner in which the direct beam is tilted during exposure of a micrograph. In the bright-field imaging mode the device provides a microscope transfer function without zeros in all spatial directions and has been used to obtain high resolution images which are also free from the effect of chromatic aberration. A standard second condenser aperture is employed and the width of the cone annulus is readily controlled by defocusing the second condenser lens. The cone azimuthal angle is also controlled electronically; hence the device can also be used in the dark-field imaging mode. This device has been applied to imaging both amorphous and crystalline materials including biomolecular specimens."}
{"id": "PMID:195375", "title": "Neuromuscular transmission in the frog at 31 ATA helium pressure.", "content": "Synaptic potentials were recorded extracellularly in in vitro frog cutaneous pectoris nerve muscle preparation in air at 1 ATA and in a hyperbaric gas environment of 1 ATA air plus 30 ATA helium. Sufficient curare was always used in the bathing solution to prevent propagated muscle action potentials upon maximal stimulation of the nerve. Shape of the synaptic potential and poststimulus facilitation and depression were compared in these two environments. No significant differences were found.", "contents": "Neuromuscular transmission in the frog at 31 ATA helium pressure. Synaptic potentials were recorded extracellularly in in vitro frog cutaneous pectoris nerve muscle preparation in air at 1 ATA and in a hyperbaric gas environment of 1 ATA air plus 30 ATA helium. Sufficient curare was always used in the bathing solution to prevent propagated muscle action potentials upon maximal stimulation of the nerve. Shape of the synaptic potential and poststimulus facilitation and depression were compared in these two environments. No significant differences were found."}
{"id": "PMID:195376", "title": "Canine urinary bladder epithelial cells: preparation for cell culture by enzyme dispersion.", "content": "In a qualitative and quantitative study of enzymic dispersion of cells from the mucosal layer stripped from canine urinary bladder, trypsin was found to be equal or superior to the other enzymes tested for dispersal of urothelial cells specifically. Collagenase or collagenase plus trypsin served to disperse the whole tissue. A procedure for recovering the urothelial cells as a single-cell suspension and establishing them in culture is presented. The morphology, culture behaviour, and chromosome complement of these cells is described.", "contents": "Canine urinary bladder epithelial cells: preparation for cell culture by enzyme dispersion. In a qualitative and quantitative study of enzymic dispersion of cells from the mucosal layer stripped from canine urinary bladder, trypsin was found to be equal or superior to the other enzymes tested for dispersal of urothelial cells specifically. Collagenase or collagenase plus trypsin served to disperse the whole tissue. A procedure for recovering the urothelial cells as a single-cell suspension and establishing them in culture is presented. The morphology, culture behaviour, and chromosome complement of these cells is described."}
{"id": "PMID:195372", "title": "Reduction of postperfusion cytomegalovirus-infections following the use of leukocyte depleted blood.", "content": "After extracorporeal perfusion some patients develop evidence of cytomegalovirus (CMV) infection. It is proposed that antigenically stimulated donor and recipient leukocytes may divide and activate latent CMV associated with leukocytes. To test this hypothesis, alternate patients were perfused with leukocyte-depleted or whole blood (controls). Four of six controls who were CMV antibody negative preoperatively seroconverted after perfusion. Virus was recovered from the blood of three and from the urine of two of these patients. One of four controls who were seropositive preoperatively developed a significant titer rise. Only one of eight patients perfused with leukocyte poor blond who were seronegative prior to surgery developed a viremia and became antibody positive; another manifested a viruria but remained antibody negative. These findings are consistent with the proposed hypothesis and suggest a means for reducing transfusion-associated CMV infections.", "contents": "Reduction of postperfusion cytomegalovirus-infections following the use of leukocyte depleted blood. After extracorporeal perfusion some patients develop evidence of cytomegalovirus (CMV) infection. It is proposed that antigenically stimulated donor and recipient leukocytes may divide and activate latent CMV associated with leukocytes. To test this hypothesis, alternate patients were perfused with leukocyte-depleted or whole blood (controls). Four of six controls who were CMV antibody negative preoperatively seroconverted after perfusion. Virus was recovered from the blood of three and from the urine of two of these patients. One of four controls who were seropositive preoperatively developed a significant titer rise. Only one of eight patients perfused with leukocyte poor blond who were seronegative prior to surgery developed a viremia and became antibody positive; another manifested a viruria but remained antibody negative. These findings are consistent with the proposed hypothesis and suggest a means for reducing transfusion-associated CMV infections."}
{"id": "PMID:195373", "title": "Electron microscopic search for endogenous type C virus production in organs of dexamethasone-treated C57BL/He and C57BL/6J mice.", "content": "Several organs of newborn or adult C57BL/He and C57BL/6J mice and of infant AKR mice were examined for type-C viral particles after treatment with dexamethasone, a corticosteroid hormone that stimulates C virus replication. In both C57BL strains C particles were consistently found in the exocrine pancreas of the newborns but in smaller number than that previously observed in the adults. No C particles were observed in the submaxillary salivary glands, bones or other organs examined in adult C57BL/He and C57BL/6J mice. In infant AKR mice, few C particles were observed in the exocrine pancreas or submaxillary salivary glands whereas they were found to be produced in large number by bone cells. The results suggest that in C57BL/He and C57BL/6J mice endogenous C particle production is continuous throughout life in the exocrine pancreas and is restricted to this tissue.", "contents": "Electron microscopic search for endogenous type C virus production in organs of dexamethasone-treated C57BL/He and C57BL/6J mice. Several organs of newborn or adult C57BL/He and C57BL/6J mice and of infant AKR mice were examined for type-C viral particles after treatment with dexamethasone, a corticosteroid hormone that stimulates C virus replication. In both C57BL strains C particles were consistently found in the exocrine pancreas of the newborns but in smaller number than that previously observed in the adults. No C particles were observed in the submaxillary salivary glands, bones or other organs examined in adult C57BL/He and C57BL/6J mice. In infant AKR mice, few C particles were observed in the exocrine pancreas or submaxillary salivary glands whereas they were found to be produced in large number by bone cells. The results suggest that in C57BL/He and C57BL/6J mice endogenous C particle production is continuous throughout life in the exocrine pancreas and is restricted to this tissue."}
{"id": "PMID:195377", "title": "Keratoplasty in infants and children.", "content": "The most common causes of acquired corneal scarring before age 6 are herpes simplex keratitis, penetrating injuries, and congenital dystrophies. We performed 18 keratoplasties in 16 eyes of 15 patients under the age of 12 years, achieving clear grafts in 14 eyes (87%). We also performed 11 grafts in nine eyes of eight patients with congenital, central corneal opacities, achieving only one clear graft and four instances of phthisis bulbi or enucleation for buphthalmos. We do not recommend penetrating keratoplasty in patients with unilateral, congenital corneal opacities. However, those with bilateral cloudy corneas should have an attempt at kertoplasty as early in life as possible. The social and psychologic condition of the family often makes the difference between success and failure.", "contents": "Keratoplasty in infants and children. The most common causes of acquired corneal scarring before age 6 are herpes simplex keratitis, penetrating injuries, and congenital dystrophies. We performed 18 keratoplasties in 16 eyes of 15 patients under the age of 12 years, achieving clear grafts in 14 eyes (87%). We also performed 11 grafts in nine eyes of eight patients with congenital, central corneal opacities, achieving only one clear graft and four instances of phthisis bulbi or enucleation for buphthalmos. We do not recommend penetrating keratoplasty in patients with unilateral, congenital corneal opacities. However, those with bilateral cloudy corneas should have an attempt at kertoplasty as early in life as possible. The social and psychologic condition of the family often makes the difference between success and failure."}
{"id": "PMID:195390", "title": "Pathomorphology of humoral, cellular and combined primary immunodeficiencies.", "content": "Histologic, immunohistologic and electron microscopic findings in three children with primary immunodeficiencies are reported. Classical X-linked infantile agammaglobulinemia Bruton was present in case 1 (male, aged 16 years), selective cellular immunodeficiency with thrombopenia in case 2 (male, aged 2 1/2 years) and non-lymphopenic severe combined immunodeficiency in case 3 (male, aged 1 3/4 years). At autopsy, all three cases exhibited unusual types of pneumonia. In case 2 a generalized cytomegalovirus infection was present. Case 3 disclosed panmyelopathia and chronic liver lesions due to severe GvH-reaction subsequent to bone marrow transplantation. A detailed morphologic study of the immune system revealed distinct alterations in the thymus, spleen, and lymph nodes and the lymphatic tissues of the gastrointestinal tract characteristic of an immunodeficiency state, either humoral (case 1), cellular (case 2) or combined (case 3).", "contents": "Pathomorphology of humoral, cellular and combined primary immunodeficiencies. Histologic, immunohistologic and electron microscopic findings in three children with primary immunodeficiencies are reported. Classical X-linked infantile agammaglobulinemia Bruton was present in case 1 (male, aged 16 years), selective cellular immunodeficiency with thrombopenia in case 2 (male, aged 2 1/2 years) and non-lymphopenic severe combined immunodeficiency in case 3 (male, aged 1 3/4 years). At autopsy, all three cases exhibited unusual types of pneumonia. In case 2 a generalized cytomegalovirus infection was present. Case 3 disclosed panmyelopathia and chronic liver lesions due to severe GvH-reaction subsequent to bone marrow transplantation. A detailed morphologic study of the immune system revealed distinct alterations in the thymus, spleen, and lymph nodes and the lymphatic tissues of the gastrointestinal tract characteristic of an immunodeficiency state, either humoral (case 1), cellular (case 2) or combined (case 3)."}
{"id": "PMID:195405", "title": "[Radioimmunological determination of ACTH and its clinical use].", "content": "Since radioimmunological methods have been introduced, it has become possible to measure the concentration of ACTH in human plasma directly. We report on first experiences with commercial testing sets. We proved the clinical usefulness of the determination of ACTH in the cases of 13 healthy adult subjects and 8 healthy children. Furthermore patients with evidence of primary adrenal insufficiency and with disturbances in the hypothalamicpituitary system were included in our investigations. The obtained values are in agreement with the known conception of the hypothalamic-pituitary-adrenal system.", "contents": "[Radioimmunological determination of ACTH and its clinical use]. Since radioimmunological methods have been introduced, it has become possible to measure the concentration of ACTH in human plasma directly. We report on first experiences with commercial testing sets. We proved the clinical usefulness of the determination of ACTH in the cases of 13 healthy adult subjects and 8 healthy children. Furthermore patients with evidence of primary adrenal insufficiency and with disturbances in the hypothalamicpituitary system were included in our investigations. The obtained values are in agreement with the known conception of the hypothalamic-pituitary-adrenal system."}
{"id": "PMID:195406", "title": "[Therapy with synthetic ACTH].", "content": "With the development of the fully-synthetic preparation (tetracosactide) the therapy with ACTH has again obtained importance. The application in internal medicine above all takes place in rheumatoid arthritis and in bronchial asthma. Advantages and disadvantages are described and the possibility of withdrawal of cortisone is especially emphasized.", "contents": "[Therapy with synthetic ACTH]. With the development of the fully-synthetic preparation (tetracosactide) the therapy with ACTH has again obtained importance. The application in internal medicine above all takes place in rheumatoid arthritis and in bronchial asthma. Advantages and disadvantages are described and the possibility of withdrawal of cortisone is especially emphasized."}
{"id": "PMID:195407", "title": "[Specific and unspecific immune stimulation in recurrent herpes simplex].", "content": "According to the present state of our knowledge the clinical picture of the recurrent herpes simplex and the recurrent stomatitis aphthosa is due to a weakness of the immune defense. It cannot be decided yet if it is but a quantitative weakness or if it is a special form of disturbance in the permeation, which allows the virus to remain alive and to reactivate after a short period of time. Injection of a specific herpes simplex vaccine (HVH-1 or HVH-2 strain) or administration of Levamisol are at present the most promising ways of treatment. Both kinds of treatment are well tolerated, they give the same results in herpes simplex recidivans labialis, and whilst in herpes simplex recidivans genitalis the vaccine should be preferred, Levamisol should be given preference in stomatitis aphthosa on account of its broad (less specific) range of action.", "contents": "[Specific and unspecific immune stimulation in recurrent herpes simplex]. According to the present state of our knowledge the clinical picture of the recurrent herpes simplex and the recurrent stomatitis aphthosa is due to a weakness of the immune defense. It cannot be decided yet if it is but a quantitative weakness or if it is a special form of disturbance in the permeation, which allows the virus to remain alive and to reactivate after a short period of time. Injection of a specific herpes simplex vaccine (HVH-1 or HVH-2 strain) or administration of Levamisol are at present the most promising ways of treatment. Both kinds of treatment are well tolerated, they give the same results in herpes simplex recidivans labialis, and whilst in herpes simplex recidivans genitalis the vaccine should be preferred, Levamisol should be given preference in stomatitis aphthosa on account of its broad (less specific) range of action."}
{"id": "PMID:195408", "title": "[Herpetic eye diseases].", "content": "The ophthalmologist differs between three forms of manifestation of the herpetic infection: 1. The superficial keratitis with involvement of the epithelium, known as keratitis punctata, stellata or dendritica. 2. The deep for: the keratitis disciformis. This is a delaged hypersensitivity against the herpes virus or its products of metabolism. 3. The metaherpetic keratopathy develops on the basis of a disturbed metabolism after relapsing, mainly deep herpetic keratitis. Therapy differs according to the forms of manifestation. The prevention of relapses is a problem. The frequency of relapses of the corneal herpes is considerably less and the intervals between the relapses are in general considerably longer than in dermatological herpes affections. Therefore, the influence on the recidivity by the drug Lupidon can be appreciated by a long-term study over several years only.", "contents": "[Herpetic eye diseases]. The ophthalmologist differs between three forms of manifestation of the herpetic infection: 1. The superficial keratitis with involvement of the epithelium, known as keratitis punctata, stellata or dendritica. 2. The deep for: the keratitis disciformis. This is a delaged hypersensitivity against the herpes virus or its products of metabolism. 3. The metaherpetic keratopathy develops on the basis of a disturbed metabolism after relapsing, mainly deep herpetic keratitis. Therapy differs according to the forms of manifestation. The prevention of relapses is a problem. The frequency of relapses of the corneal herpes is considerably less and the intervals between the relapses are in general considerably longer than in dermatological herpes affections. Therefore, the influence on the recidivity by the drug Lupidon can be appreciated by a long-term study over several years only."}
{"id": "PMID:195404", "title": "Infectious mononucleosis and mononucleosis syndromes.", "content": "Infectious mononucleosis (IM) and cytomegalovirus (CMV) mononucleosis are caused by a primary infection with related viruses, Epstein-Barr virus (EBV) and CMV. Despite the similarity of clinical manifestations, basic differences exist: (1) The heterophil antibody (HA) response is absent in CMV mononucleosis, whereas it is present in IM. (2) In IM atypical lymphocytosis reflects proliferation of B cells early and of T cells later in the disease course; in CMV mononucleosis the situation appears complex. (3) In blood, EBV is restricted to B lymphocytes, whereas CMV is found in polymorphonuclear and mononuclear leukocytes. (4) Complications of CMV mononucleosis such as hepatitis and pneumonitis may be due to virus cytopathic effect in target organs. Prominent tonsillopharyngitis with adenopathy, and visceral complications of IM are related to lymphoproliferation which is self-limited except in males with a rare familial defect in defense against EBV. Immune complex-mediated pathology may occur in both diseases. (5) CMV is frequently transmitted to a fetus in utero or to an infant during or after birth, and this occasionally leads to severe cytomegalic inclusion disease; vertical transmission of EBV appears to be exceptional. (6) Secondary EBV infections are associated with certain malignancies whereas such an association has not been recognized in the case of CMV. Toxoplasma gondii is another cause of HA-negative mononucleosis. Its complications in the heart, in skeletal muscle and in the central nervous system are related to direct invasion by the parasite. Cellular immunity plays an important role in defense against all three agents.", "contents": "Infectious mononucleosis and mononucleosis syndromes. Infectious mononucleosis (IM) and cytomegalovirus (CMV) mononucleosis are caused by a primary infection with related viruses, Epstein-Barr virus (EBV) and CMV. Despite the similarity of clinical manifestations, basic differences exist: (1) The heterophil antibody (HA) response is absent in CMV mononucleosis, whereas it is present in IM. (2) In IM atypical lymphocytosis reflects proliferation of B cells early and of T cells later in the disease course; in CMV mononucleosis the situation appears complex. (3) In blood, EBV is restricted to B lymphocytes, whereas CMV is found in polymorphonuclear and mononuclear leukocytes. (4) Complications of CMV mononucleosis such as hepatitis and pneumonitis may be due to virus cytopathic effect in target organs. Prominent tonsillopharyngitis with adenopathy, and visceral complications of IM are related to lymphoproliferation which is self-limited except in males with a rare familial defect in defense against EBV. Immune complex-mediated pathology may occur in both diseases. (5) CMV is frequently transmitted to a fetus in utero or to an infant during or after birth, and this occasionally leads to severe cytomegalic inclusion disease; vertical transmission of EBV appears to be exceptional. (6) Secondary EBV infections are associated with certain malignancies whereas such an association has not been recognized in the case of CMV. Toxoplasma gondii is another cause of HA-negative mononucleosis. Its complications in the heart, in skeletal muscle and in the central nervous system are related to direct invasion by the parasite. Cellular immunity plays an important role in defense against all three agents."}
{"id": "PMID:195410", "title": "Cytostatic efficacy of DNA-complexes of adriamycin, daunomycin and actinomycin D. I. Comparative studies in Novikoff hepatoma, human mammary carcinoma cells and human leukemic leukocytes.", "content": "Inhibitory effects of adriamycin, daunomycin, actinomycin D and of the related DNA-complexes on DNA and RNA synthesis were compared by precursor uptake studies in Novikoff hepatoma cells, human mammary carcinoma cells and human leukemia cells. In addition, nuclear RNA labelling profiles were analyzed in human acute leukemia blast cells and nucleolar RNA synthesis was studied in Novikoff hepatoma cells in vitro after incubations of the tumor cells with adriamycin and DNA-adriamycin. The studies revealed that compared to the free drugs a) the DNA complexes were generally less active with respect to inhibition of overall DNA and RNA synthesis in these divergent tumor cell types, b) characteristic differences between adriamycin and daunomycin which are related to a more rapid cellular uptake of daunomycin were still present after complexing of both drugs to calf thymus DNA, and c) the intracellular mode of action of the free antibiotics was not changed by complex formation with DNA. These results indicate that a preferential incorporation of the macromolecular complexes into the tumor cells by pinocytosis--as originally postulated by Trouet et al. (1972)--is not likely for Novikoff hepatoma cells, human mammary carcinoma cells and human acute leukemia blast cells. In contrast, it may be concluded from this study that the DNA complexes dissociate already at the outer cell membrane resulting in a generally decreased but kinetically drug-specific cellular uptake. In a second communication it will be demonstrated that these in-vitro effects do not correlate with the therapeutic efficacy efficacy of the complexed drugs in vivo.", "contents": "Cytostatic efficacy of DNA-complexes of adriamycin, daunomycin and actinomycin D. I. Comparative studies in Novikoff hepatoma, human mammary carcinoma cells and human leukemic leukocytes. Inhibitory effects of adriamycin, daunomycin, actinomycin D and of the related DNA-complexes on DNA and RNA synthesis were compared by precursor uptake studies in Novikoff hepatoma cells, human mammary carcinoma cells and human leukemia cells. In addition, nuclear RNA labelling profiles were analyzed in human acute leukemia blast cells and nucleolar RNA synthesis was studied in Novikoff hepatoma cells in vitro after incubations of the tumor cells with adriamycin and DNA-adriamycin. The studies revealed that compared to the free drugs a) the DNA complexes were generally less active with respect to inhibition of overall DNA and RNA synthesis in these divergent tumor cell types, b) characteristic differences between adriamycin and daunomycin which are related to a more rapid cellular uptake of daunomycin were still present after complexing of both drugs to calf thymus DNA, and c) the intracellular mode of action of the free antibiotics was not changed by complex formation with DNA. These results indicate that a preferential incorporation of the macromolecular complexes into the tumor cells by pinocytosis--as originally postulated by Trouet et al. (1972)--is not likely for Novikoff hepatoma cells, human mammary carcinoma cells and human acute leukemia blast cells. In contrast, it may be concluded from this study that the DNA complexes dissociate already at the outer cell membrane resulting in a generally decreased but kinetically drug-specific cellular uptake. In a second communication it will be demonstrated that these in-vitro effects do not correlate with the therapeutic efficacy efficacy of the complexed drugs in vivo."}
{"id": "PMID:195411", "title": "The combined modality approach in the treatment of inoperable small-cell anaplastic carcinoma of the lung.", "content": "The combined modality approach with combination chemotherapy (\"Comb\" or \"BACO\") and radiotherapy was used in a pilot study comprising 35 evaluable patients with inoperable small-cell anaplastic carcinoma of the lung. Treatment strategy was based on prior assessment of prognostic factors such as histology, performance status and extent of disease. Median survival time was 39.8 weeks for \"COMB\" treated patients and 21.2 weeks for \"BACO\" treated patients. Although the combined modality approach has been very helpful against a variety of human cancers it should be used with caution since not all combination chemotherapy regimens are compatible with radiotherapy. Mechanisms of interactions between cytostatic agents and X-rays are discussed with regard to enhanced tumor cell kill and possible toxic side effects.", "contents": "The combined modality approach in the treatment of inoperable small-cell anaplastic carcinoma of the lung. The combined modality approach with combination chemotherapy (\"Comb\" or \"BACO\") and radiotherapy was used in a pilot study comprising 35 evaluable patients with inoperable small-cell anaplastic carcinoma of the lung. Treatment strategy was based on prior assessment of prognostic factors such as histology, performance status and extent of disease. Median survival time was 39.8 weeks for \"COMB\" treated patients and 21.2 weeks for \"BACO\" treated patients. Although the combined modality approach has been very helpful against a variety of human cancers it should be used with caution since not all combination chemotherapy regimens are compatible with radiotherapy. Mechanisms of interactions between cytostatic agents and X-rays are discussed with regard to enhanced tumor cell kill and possible toxic side effects."}
{"id": "PMID:195412", "title": "[The preparation of three dehydrogenases and two kinases from pig heart by a single procedure (author's transl)].", "content": "A single procedure for the preparation of lactate dehydrogenase (EC 1.1.1.27), the mitochondrial and cytoplasmic forms of malate dehydrogenase (EC 1.1.1.37), adenylate kinase (EC 2.7.4.3) and pyruvate kinase (EC 2.7.1.40) from pig heart is described. The five enzymes are obtained in preparative amounts in homogenous form with specific activities equal to or higher than those previously reported. Some molecular properties of pig heart pyruvate kinase are determined.", "contents": "[The preparation of three dehydrogenases and two kinases from pig heart by a single procedure (author's transl)]. A single procedure for the preparation of lactate dehydrogenase (EC 1.1.1.27), the mitochondrial and cytoplasmic forms of malate dehydrogenase (EC 1.1.1.37), adenylate kinase (EC 2.7.4.3) and pyruvate kinase (EC 2.7.1.40) from pig heart is described. The five enzymes are obtained in preparative amounts in homogenous form with specific activities equal to or higher than those previously reported. Some molecular properties of pig heart pyruvate kinase are determined."}
{"id": "PMID:195413", "title": "Inhibition of human prolyl hydroxylase as common biochemical denominator of the non-sedative effects of thalidomide in man.", "content": "The two main non-sedative effects of thalidomide (2-phtalimido-glutarimide) in man are the embryopathy, which finally forced termination of its use as a sedative, and the excellent efficacy in leprosy reactions, alone for whose prevention and treatment the drug is still available. Both effects can be explained on the molecular level by assuming that a non-sedative metabolite of thalidomide mediates inhibition of human prolyl hydroxylase, as suggested by steric considerations and correlation to known data. This metabolite may well be a suitable model compound for drugs designed for selective fibrosuppression and selective immunosuppression.", "contents": "Inhibition of human prolyl hydroxylase as common biochemical denominator of the non-sedative effects of thalidomide in man. The two main non-sedative effects of thalidomide (2-phtalimido-glutarimide) in man are the embryopathy, which finally forced termination of its use as a sedative, and the excellent efficacy in leprosy reactions, alone for whose prevention and treatment the drug is still available. Both effects can be explained on the molecular level by assuming that a non-sedative metabolite of thalidomide mediates inhibition of human prolyl hydroxylase, as suggested by steric considerations and correlation to known data. This metabolite may well be a suitable model compound for drugs designed for selective fibrosuppression and selective immunosuppression."}
{"id": "PMID:195419", "title": "Liver disease in Papua New Guinea.", "content": "This paper gives, in detail, the causes of either liver disease or hepatomegaly in 100 patients, mostly adults, admitted to the medical wards of Angau Memorial Hospital, Lae, during 1968 and 1969. The major findings included liver cell carcinoma, cirrhosis (often with chronic active hepatitis), tropical splenomegaly, pericholangitis and hepatitis. There were 27 with miscellaneous findings including ten with normal, or almost normal, livers despite the definite enlargement. Patients with liver cell carcinoma presented late in the course of their illness and had a poor prognosis. Others, with pericholangitis, had clinical features of portal hypertension indistinguishable from that complicated cirrhosis. There was an unexpected number with chronic active hepatitis and a liver biopsy is essential for such a diagnosis. Hepatic sinusoidal lymphocytosis is almost invariably found in patients with TS but may occasionally be found in those with a non-palpable spleen. Patients with right heart failure of chronic respiratory disease, and jaundice of acute pneumonia were excluded from the study.", "contents": "Liver disease in Papua New Guinea. This paper gives, in detail, the causes of either liver disease or hepatomegaly in 100 patients, mostly adults, admitted to the medical wards of Angau Memorial Hospital, Lae, during 1968 and 1969. The major findings included liver cell carcinoma, cirrhosis (often with chronic active hepatitis), tropical splenomegaly, pericholangitis and hepatitis. There were 27 with miscellaneous findings including ten with normal, or almost normal, livers despite the definite enlargement. Patients with liver cell carcinoma presented late in the course of their illness and had a poor prognosis. Others, with pericholangitis, had clinical features of portal hypertension indistinguishable from that complicated cirrhosis. There was an unexpected number with chronic active hepatitis and a liver biopsy is essential for such a diagnosis. Hepatic sinusoidal lymphocytosis is almost invariably found in patients with TS but may occasionally be found in those with a non-palpable spleen. Patients with right heart failure of chronic respiratory disease, and jaundice of acute pneumonia were excluded from the study."}
{"id": "PMID:195414", "title": "Purification of a glycoprotein from bovine leukemia virus (BLV).", "content": "A precipitating antigen of bovine leukemia virus was isolated by isoelectric focusing and Sephadex gel filtration. In SDS-polyacrylamide gel electrophoresis it was found to be a homogeneous protein with a relative molecular weight of 69000 daltons. Because of its relative molecular weight and staining characteristics it was designated as BLV gp69. A protein with the same molecular weight could also be demonstrated in BLV particles. In 34 out of 35 sera from cattle affected by enzootic bovine leukosis antibodies against gp69 were detected, whereas the sera from 197 animals, free of bovine leukosis, did not react in immunodiffusion test.", "contents": "Purification of a glycoprotein from bovine leukemia virus (BLV). A precipitating antigen of bovine leukemia virus was isolated by isoelectric focusing and Sephadex gel filtration. In SDS-polyacrylamide gel electrophoresis it was found to be a homogeneous protein with a relative molecular weight of 69000 daltons. Because of its relative molecular weight and staining characteristics it was designated as BLV gp69. A protein with the same molecular weight could also be demonstrated in BLV particles. In 34 out of 35 sera from cattle affected by enzootic bovine leukosis antibodies against gp69 were detected, whereas the sera from 197 animals, free of bovine leukosis, did not react in immunodiffusion test."}
{"id": "PMID:195416", "title": "African green monkey fibroblast actin morphology during SV40 infection.", "content": "Monkey skin fibroblasts were infected with simian virus 40. Cells that exhibited the viral tumor antigen were found to retain the normal morphology of actin filaments up to six days after infection. However when cells were transformed in terms of focus formation they had lost the normal actin morphology.", "contents": "African green monkey fibroblast actin morphology during SV40 infection. Monkey skin fibroblasts were infected with simian virus 40. Cells that exhibited the viral tumor antigen were found to retain the normal morphology of actin filaments up to six days after infection. However when cells were transformed in terms of focus formation they had lost the normal actin morphology."}
{"id": "PMID:195415", "title": "[Isolation and characterization of a membrane-bound pyruvate dehydrogenase complex from the phototrophic bacterium Rhodospirillum rubrum (author's transl)].", "content": "The pyruvate dehydrogenase complex from the photosynthetic bacterium Rhodospirillum rubrum was associated with the membrane fraction both in heterotrophically and photosynthetically grown cells. The complex was separated from the membranes and partially purified by precipitation with MgSO4 and gelfiltration through Sepharose 4B. The purified complex had a specific activity of 1.5-2mumol/min-mg protein and contained the following partial activities: pyruvate dehydrogenase (EC 1.2.4.1), dihydrolipoamide transacetylase (EC 2.3.1.12) and dihydrolipoamide dehydrogenase (EC 1.6.4.3). Contrary to other bacterial pyruvate dehydrogenase complexes, the enzyme  complex from R. rubrum revealed no cooperatively between pyruvate binding sites. The kinetic constants (Km) for the overall reaction were (in mM): 0.14 (pyruvate), 0.07 (NAD) and 0.025 (coenzyme A). The Km for thiamine pyrophosphate was dependent on the nature and the concentration of the divalent metal ion (Mn or Mg) present in the reaction mixture, the values ranging from 0.5 to 3 micrometer. NADH was a potent inhibitor (Ki=5 micrometer) of the enzyme complex and the dihydrolipo amide dehydrogenase. The inhibition was competitive with respect to NAD. In addition to its rapid inhibitory effect, NADH also inactivated the enzyme. Cysteine partially protected the enzyme complex against NADH-inactivation. Acetyl-coenzyme A also inhibited the overall reaction (Ki=40 micrometer). The inhibition was dependent on the concentration of coenzyme A, but independent of the concentration of pyruvate. Sugar phosphates, phosphoenolpyruvate, citric acid cycle intermediates and nucleosidephosphates (1 mM) had no pronounced effect on the overall reaction.", "contents": "[Isolation and characterization of a membrane-bound pyruvate dehydrogenase complex from the phototrophic bacterium Rhodospirillum rubrum (author's transl)]. The pyruvate dehydrogenase complex from the photosynthetic bacterium Rhodospirillum rubrum was associated with the membrane fraction both in heterotrophically and photosynthetically grown cells. The complex was separated from the membranes and partially purified by precipitation with MgSO4 and gelfiltration through Sepharose 4B. The purified complex had a specific activity of 1.5-2mumol/min-mg protein and contained the following partial activities: pyruvate dehydrogenase (EC 1.2.4.1), dihydrolipoamide transacetylase (EC 2.3.1.12) and dihydrolipoamide dehydrogenase (EC 1.6.4.3). Contrary to other bacterial pyruvate dehydrogenase complexes, the enzyme  complex from R. rubrum revealed no cooperatively between pyruvate binding sites. The kinetic constants (Km) for the overall reaction were (in mM): 0.14 (pyruvate), 0.07 (NAD) and 0.025 (coenzyme A). The Km for thiamine pyrophosphate was dependent on the nature and the concentration of the divalent metal ion (Mn or Mg) present in the reaction mixture, the values ranging from 0.5 to 3 micrometer. NADH was a potent inhibitor (Ki=5 micrometer) of the enzyme complex and the dihydrolipo amide dehydrogenase. The inhibition was competitive with respect to NAD. In addition to its rapid inhibitory effect, NADH also inactivated the enzyme. Cysteine partially protected the enzyme complex against NADH-inactivation. Acetyl-coenzyme A also inhibited the overall reaction (Ki=40 micrometer). The inhibition was dependent on the concentration of coenzyme A, but independent of the concentration of pyruvate. Sugar phosphates, phosphoenolpyruvate, citric acid cycle intermediates and nucleosidephosphates (1 mM) had no pronounced effect on the overall reaction."}
{"id": "PMID:195426", "title": "Activity of chromatin-bound protease from rat liver and Morris hepatomas.", "content": "1. The activity of serine protease was studied in chromatin and in histone preparations from rat liver and Morris hepatomas, lines 5123 D and 7777. 2. Electrophoretic patterns of histones and the amounts of acid-soluble peptides released during incubation of chromatin and histones showed that there was no significant correlation between protease activity and tumour differentiation and its growth rate.", "contents": "Activity of chromatin-bound protease from rat liver and Morris hepatomas. 1. The activity of serine protease was studied in chromatin and in histone preparations from rat liver and Morris hepatomas, lines 5123 D and 7777. 2. Electrophoretic patterns of histones and the amounts of acid-soluble peptides released during incubation of chromatin and histones showed that there was no significant correlation between protease activity and tumour differentiation and its growth rate."}
{"id": "PMID:195427", "title": "The plant aminoacyl-tRNA synthetases. Effect of sodium chloride on tRNA aminoacylation and aminoacyl-tRNA decomposition catalysed by aminoacyl-tRNA synthetases from yellow lupin seeds.", "content": "The initial velocity and the extent of aminoacylation are affected by sodium chloride in the lupin aminoacylation systems involving serine, isoleucine, lysine, leucine, phenylalanine and valine. Pyrophosphorolysis and enzymatic hydrolysis of [14C]Val-tRNA catalysed by lupin valyl-tRNA synthetase are inhibited by sodium chloride nearly to the same extent. Evidence is presented that when a limiting amount of synthetase is used, the equilibrium of the aminoacylation reaction in the lupin valine system is determined only by the rate of aminoacylation and non-enzymatic deacylation of aminoacyl-tRNA, the former but not the latter reaction being dependent on concentration of the enzyme and monovalent salt.", "contents": "The plant aminoacyl-tRNA synthetases. Effect of sodium chloride on tRNA aminoacylation and aminoacyl-tRNA decomposition catalysed by aminoacyl-tRNA synthetases from yellow lupin seeds. The initial velocity and the extent of aminoacylation are affected by sodium chloride in the lupin aminoacylation systems involving serine, isoleucine, lysine, leucine, phenylalanine and valine. Pyrophosphorolysis and enzymatic hydrolysis of [14C]Val-tRNA catalysed by lupin valyl-tRNA synthetase are inhibited by sodium chloride nearly to the same extent. Evidence is presented that when a limiting amount of synthetase is used, the equilibrium of the aminoacylation reaction in the lupin valine system is determined only by the rate of aminoacylation and non-enzymatic deacylation of aminoacyl-tRNA, the former but not the latter reaction being dependent on concentration of the enzyme and monovalent salt."}
{"id": "PMID:195428", "title": "[Proof of adenylate cyclase activity in the coronary artery of cattle].", "content": "In two fractions obtained from the bovine A. coronaria adenylate cyclase activity was identified and characterized. The adenylate cyclase activity of the 75,000 X g sediment shows a pH optimum at 7.4. The temperature dependence of this adenylate cyclase activity is linear when represented in the Arrhenius plot, and an Arrhenius activation energy of 13.2 kcal Mol-1 can be calculated for the enzyme reaction. The Km-value of the enzyme to ATP is 6 +/- 0.6 - 10(-4) M. The adenylate cyclase activity of the 75,000 X g sediment can be stimulated by NaF. 5'AMP and adenosine inhibit the adenylate cyclase activity of the 75,000 X g sediment. With regard to the enzyme activity, Mn++ and Co++ replace Mg++, but not Ca++. The monovalentcations Na+ and K+ do not influence the adenylate cyclase activity. In a particulate fraction containing plasma membranes, adenylate cyclase activity was also identified. This adenylate cyclase activity can be stimulated by catecholamines, noradrenaline, and isoproterenol. This stimulation can, however, only be proved for the enzyme in the coronaries of 9-week-old and 2-year-old animals. The adenylate cyclase activity from the coronaries of adult animals is not affected by catecholamines. These findings are discussed with regard to hypertension frequently found in adult animals.", "contents": "[Proof of adenylate cyclase activity in the coronary artery of cattle]. In two fractions obtained from the bovine A. coronaria adenylate cyclase activity was identified and characterized. The adenylate cyclase activity of the 75,000 X g sediment shows a pH optimum at 7.4. The temperature dependence of this adenylate cyclase activity is linear when represented in the Arrhenius plot, and an Arrhenius activation energy of 13.2 kcal Mol-1 can be calculated for the enzyme reaction. The Km-value of the enzyme to ATP is 6 +/- 0.6 - 10(-4) M. The adenylate cyclase activity of the 75,000 X g sediment can be stimulated by NaF. 5'AMP and adenosine inhibit the adenylate cyclase activity of the 75,000 X g sediment. With regard to the enzyme activity, Mn++ and Co++ replace Mg++, but not Ca++. The monovalentcations Na+ and K+ do not influence the adenylate cyclase activity. In a particulate fraction containing plasma membranes, adenylate cyclase activity was also identified. This adenylate cyclase activity can be stimulated by catecholamines, noradrenaline, and isoproterenol. This stimulation can, however, only be proved for the enzyme in the coronaries of 9-week-old and 2-year-old animals. The adenylate cyclase activity from the coronaries of adult animals is not affected by catecholamines. These findings are discussed with regard to hypertension frequently found in adult animals."}
{"id": "PMID:195429", "title": "5-Formyl-2'-deoxyuridine: cytostatic and antiviral properties and possible modes of action.", "content": "5-Formyl-2'-deoxyuridine (fdUrd) was prepared by a new method starting from thymidine and investigated for its influence both on proliferation of cultured mammalian cells and virus replication in vitro. The compound was found to have strong cytostatic and antiviral properties: 50% inhibition of proliferation of BHK 21/C13 cells or Ehrlich ascites tumour cells (EAT) was obtained at 4 - 10(-6) and 6 - 10(-6) M, respectively, while the treatment of pseudorabies virus with the same concentration resulted in about 1.5 log reduction of virus yield. A concentration of 1 - 10(-4) M inhibited cell proliferation by 80 to 100% while the virus yield was reduced by more than 3 orders of magnitude. All inhibitions can be prevented by thymidine.--DNA synthesis of EAT cells in vitro, as estimated by incorporation of [32P]-phosphate or low concentrations of [3H]-thymidine, was inhibited. Further biochemical experiments have provided indirect evidence that the compound is phosphorylated by thymidine and thymidylate phosphorylating enzymes. An inhibition of cell free DNA synthesis was found to be depending on a given period of preincubation with the compound (supposed to be needed for the formation of fdUrd 5'-triphosphate). This suggests that the 5'-triphosphate of fdUrd is an inhibitor of DNA polymerases and--by analogy with experiments with 5-formyluridine-5'-triphosphate and RNA polymerases [14]--may be used as an affinity label for this group of enzymes. It is concluded that the described cytostatic and antiviral effects of fdUrd are due to an intracellular \"lethal\" synthesis of the relevant phosphates which inhibit thymidylate synthetase (as had been found earlier to occur with the chemically prepared nucleotide in cell free extracts [1, 2]) and DNA synthesizing enzymes.", "contents": "5-Formyl-2'-deoxyuridine: cytostatic and antiviral properties and possible modes of action. 5-Formyl-2'-deoxyuridine (fdUrd) was prepared by a new method starting from thymidine and investigated for its influence both on proliferation of cultured mammalian cells and virus replication in vitro. The compound was found to have strong cytostatic and antiviral properties: 50% inhibition of proliferation of BHK 21/C13 cells or Ehrlich ascites tumour cells (EAT) was obtained at 4 - 10(-6) and 6 - 10(-6) M, respectively, while the treatment of pseudorabies virus with the same concentration resulted in about 1.5 log reduction of virus yield. A concentration of 1 - 10(-4) M inhibited cell proliferation by 80 to 100% while the virus yield was reduced by more than 3 orders of magnitude. All inhibitions can be prevented by thymidine.--DNA synthesis of EAT cells in vitro, as estimated by incorporation of [32P]-phosphate or low concentrations of [3H]-thymidine, was inhibited. Further biochemical experiments have provided indirect evidence that the compound is phosphorylated by thymidine and thymidylate phosphorylating enzymes. An inhibition of cell free DNA synthesis was found to be depending on a given period of preincubation with the compound (supposed to be needed for the formation of fdUrd 5'-triphosphate). This suggests that the 5'-triphosphate of fdUrd is an inhibitor of DNA polymerases and--by analogy with experiments with 5-formyluridine-5'-triphosphate and RNA polymerases [14]--may be used as an affinity label for this group of enzymes. It is concluded that the described cytostatic and antiviral effects of fdUrd are due to an intracellular \"lethal\" synthesis of the relevant phosphates which inhibit thymidylate synthetase (as had been found earlier to occur with the chemically prepared nucleotide in cell free extracts [1, 2]) and DNA synthesizing enzymes."}
{"id": "PMID:195430", "title": "Maternal plasma triglycerides as a source of fetal fatty acids.", "content": "The transfer of plasma triglyceride fatty acids from mother to fetus was studied in rats. Following i.v. injection of labelled chylomicron and very low density lipoprotein (VLDL) triglycerides into the mother, the time courses of the plasma triglycerides, free fatty acids, and fetal radioactivity were determined. The data were analysed using a mathematical model. From the results the following conclusions were drawn: To cover the need of fetal fatty acids, the placenta utilizes only VLDL triglycerides but not chylomicron triglycerides. Comparison of the amount of VLDL triglyceride fatty acids (0.04 micromoles/min/litter) and of maternal plasma free fatty acids (0.08 micronmoles/min/litter) transferred into the fetus indicates that the maternal plasma triglycerides are a source of fetal fatty acids, that cannot be neglected.", "contents": "Maternal plasma triglycerides as a source of fetal fatty acids. The transfer of plasma triglyceride fatty acids from mother to fetus was studied in rats. Following i.v. injection of labelled chylomicron and very low density lipoprotein (VLDL) triglycerides into the mother, the time courses of the plasma triglycerides, free fatty acids, and fetal radioactivity were determined. The data were analysed using a mathematical model. From the results the following conclusions were drawn: To cover the need of fetal fatty acids, the placenta utilizes only VLDL triglycerides but not chylomicron triglycerides. Comparison of the amount of VLDL triglyceride fatty acids (0.04 micromoles/min/litter) and of maternal plasma free fatty acids (0.08 micronmoles/min/litter) transferred into the fetus indicates that the maternal plasma triglycerides are a source of fetal fatty acids, that cannot be neglected."}
{"id": "PMID:195431", "title": "Principle and application of a multicuvette for determination of enzyme activities and substrate concentrations in microsamples.", "content": "A method of photometric analysis is described that allows to determine enzyme activities or substrate concentrations of 50 samples simultaneously in a multicuvette. Test volume is in the range of 30-85 micronl, light path between 0.5 and 2.0 mm. The testing principle can be used for colorimetric measurements and for NADH dependent reactions as well. The procedure is particularly suited for kinetic determinations. Variation coefficients for determinations of substrate concentrations and enzyme activities are in the range of conventional enzymatic tests.", "contents": "Principle and application of a multicuvette for determination of enzyme activities and substrate concentrations in microsamples. A method of photometric analysis is described that allows to determine enzyme activities or substrate concentrations of 50 samples simultaneously in a multicuvette. Test volume is in the range of 30-85 micronl, light path between 0.5 and 2.0 mm. The testing principle can be used for colorimetric measurements and for NADH dependent reactions as well. The procedure is particularly suited for kinetic determinations. Variation coefficients for determinations of substrate concentrations and enzyme activities are in the range of conventional enzymatic tests."}
{"id": "PMID:195432", "title": "[Chacterization of human reticulocytes: respiration, Pasteur effect, and electron microscopic findings on mitochondria].", "content": "On 5 blood samples of newborns, whose reticulocytes had been enriched by density gradient centrifugation, and on 25 blood samples of different reticulocytoses of man were determined: the extent of intra- and extramitochondrial respiration, coupling of the electron transfer with the oxidative phosphorylation and the electronmicroscopic appearance, and the number of mitochondria. The reticulocytes occurring in the flowing human blood are in general relatively stiff and are characterized by the following properties:--low respiration--low capacity of the respiratory chain enzymes--weakened Pasteur effect --varying proportion of intramitochondrial respiration and total respiration--decoupling of a major part of the intramitochondrial respiration--low number of mitochondria--qualitative changes of mitochondria. However, there are situations of erythropoiesis where immature reticulocytes are discharged in man (similar to the socalled \"stress reticulocytes\" of rabbits). On the other hand, it could be shown that the reticulocytes of rabbits are mature in the normal state.", "contents": "[Chacterization of human reticulocytes: respiration, Pasteur effect, and electron microscopic findings on mitochondria]. On 5 blood samples of newborns, whose reticulocytes had been enriched by density gradient centrifugation, and on 25 blood samples of different reticulocytoses of man were determined: the extent of intra- and extramitochondrial respiration, coupling of the electron transfer with the oxidative phosphorylation and the electronmicroscopic appearance, and the number of mitochondria. The reticulocytes occurring in the flowing human blood are in general relatively stiff and are characterized by the following properties:--low respiration--low capacity of the respiratory chain enzymes--weakened Pasteur effect --varying proportion of intramitochondrial respiration and total respiration--decoupling of a major part of the intramitochondrial respiration--low number of mitochondria--qualitative changes of mitochondria. However, there are situations of erythropoiesis where immature reticulocytes are discharged in man (similar to the socalled \"stress reticulocytes\" of rabbits). On the other hand, it could be shown that the reticulocytes of rabbits are mature in the normal state."}
{"id": "PMID:195433", "title": "[Inoperable carcinoma of the stomach in exploratory laparotomy].", "content": "For the last few years we made 52 exploratory laparotomies. All the patients were treated clinically, through laboratories, with X-rays, and for a while ago by means of gastroscopy. A radical surgical operation was planned for each of them we made radical operation in 12 cases only, and 14 GEA. For all others we made pure exploratory laparotomy with probatory excision. Considering such inauspicious results, it is necessary to give maximum consideration to early detected gastric cancer. In a matter of critical age persons after 40, the attention must be referred to anamnestically suspect cases. For this purpose, the early detailed treatment by the latest diagnostic methods must be done. If in such treated cases there is even the smallest doubt of a malignant process, it is needful not to abstain from diagnostic exploratory laparotomy.", "contents": "[Inoperable carcinoma of the stomach in exploratory laparotomy]. For the last few years we made 52 exploratory laparotomies. All the patients were treated clinically, through laboratories, with X-rays, and for a while ago by means of gastroscopy. A radical surgical operation was planned for each of them we made radical operation in 12 cases only, and 14 GEA. For all others we made pure exploratory laparotomy with probatory excision. Considering such inauspicious results, it is necessary to give maximum consideration to early detected gastric cancer. In a matter of critical age persons after 40, the attention must be referred to anamnestically suspect cases. For this purpose, the early detailed treatment by the latest diagnostic methods must be done. If in such treated cases there is even the smallest doubt of a malignant process, it is needful not to abstain from diagnostic exploratory laparotomy."}
{"id": "PMID:195434", "title": "[The gastric syndrome in total gastrectomy using Longmire's technic and its surgical treatment].", "content": "Evaluating total gastrectomy Longmire's method in 78 cases, authors analyze appearance of symptomatology and pathological processes of agastrical syndrome. On basis of own 15-years experience, authors believe reconstruction sec. Longmire as most physiological and with minimum negative consequences successful controlled by substitutional vitamin -- enzymatic therapy.", "contents": "[The gastric syndrome in total gastrectomy using Longmire's technic and its surgical treatment]. Evaluating total gastrectomy Longmire's method in 78 cases, authors analyze appearance of symptomatology and pathological processes of agastrical syndrome. On basis of own 15-years experience, authors believe reconstruction sec. Longmire as most physiological and with minimum negative consequences successful controlled by substitutional vitamin -- enzymatic therapy."}
{"id": "PMID:195435", "title": "Ganglioside content and pattern in human gliomas in culture. Correlation of morphological changes with altered gangliosides.", "content": "The ganglioside level and pattern of human gliomas in monolayer cultures were examined. These gliomas revealed morphological variations that correlated with several features of ganglioside analysis. Glioblastoma lines TC 178 and TC 501 that morphologically had changed during extended subculture revealed reduced amounts and a simplified pattern of gangliosides with almost total loss of the characteristic brain complex gangliosides. In contrast, two glioblastoma lines TC 526 and TC 593, as well as the oligodendroglioma line TC 620 showed brain-like gangliosides and the cells in these cultures had maintained their characteristic morphology observed during early subcultures. The possibility that altered ganglioside levels occur in conjunction with morphological changes after propagation in vitro is discussed.", "contents": "Ganglioside content and pattern in human gliomas in culture. Correlation of morphological changes with altered gangliosides. The ganglioside level and pattern of human gliomas in monolayer cultures were examined. These gliomas revealed morphological variations that correlated with several features of ganglioside analysis. Glioblastoma lines TC 178 and TC 501 that morphologically had changed during extended subculture revealed reduced amounts and a simplified pattern of gangliosides with almost total loss of the characteristic brain complex gangliosides. In contrast, two glioblastoma lines TC 526 and TC 593, as well as the oligodendroglioma line TC 620 showed brain-like gangliosides and the cells in these cultures had maintained their characteristic morphology observed during early subcultures. The possibility that altered ganglioside levels occur in conjunction with morphological changes after propagation in vitro is discussed."}
{"id": "PMID:195436", "title": "Ultrastructural study of the vacuoles in the peripheral lymphocytes in juvenile amaurotic idiocy. Juvenile form of generalized ceroid lipofuscinosis.", "content": "Lymphocytes of the peripheral blood of 31 patients with juvenile amaurotic idiocy (juvenile form of ceroid lipofuscinosis) were examined with the electron microscope. In all cases, intracytoplasmic clear vacuoles were present, containing round hollow, fingerprint and highly electron dense structures. The combination of these structures, not necessarily in one and the same vacuole, was considered to be highly indicative for the diagnosis of juvenile amaurotic idiocy. In addition to these three structures, parallel tubular inclusion bodies, rectilinear profiles and rod-shaped structures were found but in a number of the cases. The parallel tubular inclusion bodies were not regarded as having any diagnostic significance.", "contents": "Ultrastructural study of the vacuoles in the peripheral lymphocytes in juvenile amaurotic idiocy. Juvenile form of generalized ceroid lipofuscinosis. Lymphocytes of the peripheral blood of 31 patients with juvenile amaurotic idiocy (juvenile form of ceroid lipofuscinosis) were examined with the electron microscope. In all cases, intracytoplasmic clear vacuoles were present, containing round hollow, fingerprint and highly electron dense structures. The combination of these structures, not necessarily in one and the same vacuole, was considered to be highly indicative for the diagnosis of juvenile amaurotic idiocy. In addition to these three structures, parallel tubular inclusion bodies, rectilinear profiles and rod-shaped structures were found but in a number of the cases. The parallel tubular inclusion bodies were not regarded as having any diagnostic significance."}
{"id": "PMID:195437", "title": "Atypical subacute sclerosing panencephalitis.", "content": "An unusual case of panencephalitis in a 4-year-old Japanese boy, with onset at three months after measles infection and rapid progression to a comatose state in approximately one month, is described. A rapid rise in serum measles antibody titre after the onset of the symptoms, and the appearance of various abnormal antibodies in the serum, were noted. Pathologically, the brain showed sclerosing polio- and leucoencephalitis with diffuse gliosis and sporadic intranuclear inclusions. The process is suggested to be intermediate or transitional between acute measles encephalitis and SSPE.", "contents": "Atypical subacute sclerosing panencephalitis. An unusual case of panencephalitis in a 4-year-old Japanese boy, with onset at three months after measles infection and rapid progression to a comatose state in approximately one month, is described. A rapid rise in serum measles antibody titre after the onset of the symptoms, and the appearance of various abnormal antibodies in the serum, were noted. Pathologically, the brain showed sclerosing polio- and leucoencephalitis with diffuse gliosis and sporadic intranuclear inclusions. The process is suggested to be intermediate or transitional between acute measles encephalitis and SSPE."}
{"id": "PMID:195438", "title": "Hematogenous metastases of carcinoma to dorsal root ganglia.", "content": "Hematogenous metastases of carcinoma to dorsal root ganglia was found in 2 of approximately 500 consecutive autopsies in which a lumbar dorsal root ganglion was routinely examined microscopically. The primary tumors were poorly differentiated colonic adenocarcinoma and oat cell carcinoma of the lung, both with widespread hematogenous metastases which spared the central nervous system. No symptoms were detected clinically. In the same series of patients the sural nerve as well as the lumbar plexus were histologically sampled but no examples of distant endoneurial metastases were found. The vascular endothelium of dorsal root ganglia is fenestrated and, presumably as a consequence, provides no blood-ganglion barrier. This microvascular difference may account for the susceptibility of the ganglia to metastases when compared to nerve trunks which posses unfenestrated endothelium and blood-nerve barrier.", "contents": "Hematogenous metastases of carcinoma to dorsal root ganglia. Hematogenous metastases of carcinoma to dorsal root ganglia was found in 2 of approximately 500 consecutive autopsies in which a lumbar dorsal root ganglion was routinely examined microscopically. The primary tumors were poorly differentiated colonic adenocarcinoma and oat cell carcinoma of the lung, both with widespread hematogenous metastases which spared the central nervous system. No symptoms were detected clinically. In the same series of patients the sural nerve as well as the lumbar plexus were histologically sampled but no examples of distant endoneurial metastases were found. The vascular endothelium of dorsal root ganglia is fenestrated and, presumably as a consequence, provides no blood-ganglion barrier. This microvascular difference may account for the susceptibility of the ganglia to metastases when compared to nerve trunks which posses unfenestrated endothelium and blood-nerve barrier."}
{"id": "PMID:195443", "title": "Statistical analysis of factors affecting survival after glioblastoma multiforme.", "content": "Statistical evaluation of 71 cases (adults) of histologically confirmed supratentorial surgically treated glioblastoma multiforme seen during the period 1958 to 1973 revealed that the state of calcification as determined by roentgenography and the histological appearance of the neoplasm appeared to have a relationship with the postoperative period of survival. Postoperative adjuvant treatment, location of the neoplasm, duration of preoperative symptoms, patient's age at onset, preoperative condition, and cystic formation in the neoplasm also appeared to have a relationship, although it was slight.", "contents": "Statistical analysis of factors affecting survival after glioblastoma multiforme. Statistical evaluation of 71 cases (adults) of histologically confirmed supratentorial surgically treated glioblastoma multiforme seen during the period 1958 to 1973 revealed that the state of calcification as determined by roentgenography and the histological appearance of the neoplasm appeared to have a relationship with the postoperative period of survival. Postoperative adjuvant treatment, location of the neoplasm, duration of preoperative symptoms, patient's age at onset, preoperative condition, and cystic formation in the neoplasm also appeared to have a relationship, although it was slight."}
{"id": "PMID:195444", "title": "Supratentorial recurrences of gliomas. Morphological studies in relation to time intervals with astrocytomas.", "content": "We report 137 recurrent supratentorial astrocytomas. The primary tumours diagnosed on the basis of a grading system with three stages were 72 astrocytomas I and 65 astrocytomas II. In the first group 14% of the recurrences were not changed, 55.5% became astrocytomas II, and 30.5% became glioblastomas. In the second group 55.4% were unchanged, and 44.6% became glioblastomas. The postoperative intervals untile reintervention or death were statistically examined. It seems that the recurrence time chielfy depends on the nature of the primary tumour. The transformation of an astrocytoma I to a glioblastoma takes longer than the transformation of an astrocytoma II into a glioblastoma. In about two thirds of all astrocytomas an increase of malignancy is to be expected. From the histological picture it is not possible in an individual case to predict the likelihood or speed of malignant change. With regard to the effect of irradiation the authors conclude that radiotherapy most probably does not produce malignancy.", "contents": "Supratentorial recurrences of gliomas. Morphological studies in relation to time intervals with astrocytomas. We report 137 recurrent supratentorial astrocytomas. The primary tumours diagnosed on the basis of a grading system with three stages were 72 astrocytomas I and 65 astrocytomas II. In the first group 14% of the recurrences were not changed, 55.5% became astrocytomas II, and 30.5% became glioblastomas. In the second group 55.4% were unchanged, and 44.6% became glioblastomas. The postoperative intervals untile reintervention or death were statistically examined. It seems that the recurrence time chielfy depends on the nature of the primary tumour. The transformation of an astrocytoma I to a glioblastoma takes longer than the transformation of an astrocytoma II into a glioblastoma. In about two thirds of all astrocytomas an increase of malignancy is to be expected. From the histological picture it is not possible in an individual case to predict the likelihood or speed of malignant change. With regard to the effect of irradiation the authors conclude that radiotherapy most probably does not produce malignancy."}
{"id": "PMID:195451", "title": "Technetium-99m pyrophosphate myocardial uptake in patients with stable angina pectoris.", "content": "99m-technetium (Tc) pyrophosphate myocardial scintigrams of 55 patients with stable angina pectoris were compared with those of 13 normal subjects. The mean scintigraphic score, obtained by averaging the blinded interpretations of four readers scoring on an integral scale from 0 to 4, was significantly higher for the patients with angina than for the control subjects (1.36 compared with 0.48, P less than 0.001). Among the patients with angina, those who had a prior myocardial infarction had a higher mean scintigraphic grade than those without a previous infarction (1.73 versus 1.15, P less than 0.005), and the mean grade in both groups was higher than that of control subjects (P less than 0.001). Radionuclide uptake was predominantly diffuse in the patients with angina pectoris (70%), although in those with greater uptake accumulation tended to be localized. Three of the 68 subjects had high levels of radionuclide uptake but no clinical evidence of acute myocardial injury. This study demonstrates that excess myocardial accumulation of 99m-Tc pyrophosphate can occur in patients with stable angina pectoris.", "contents": "Technetium-99m pyrophosphate myocardial uptake in patients with stable angina pectoris. 99m-technetium (Tc) pyrophosphate myocardial scintigrams of 55 patients with stable angina pectoris were compared with those of 13 normal subjects. The mean scintigraphic score, obtained by averaging the blinded interpretations of four readers scoring on an integral scale from 0 to 4, was significantly higher for the patients with angina than for the control subjects (1.36 compared with 0.48, P less than 0.001). Among the patients with angina, those who had a prior myocardial infarction had a higher mean scintigraphic grade than those without a previous infarction (1.73 versus 1.15, P less than 0.005), and the mean grade in both groups was higher than that of control subjects (P less than 0.001). Radionuclide uptake was predominantly diffuse in the patients with angina pectoris (70%), although in those with greater uptake accumulation tended to be localized. Three of the 68 subjects had high levels of radionuclide uptake but no clinical evidence of acute myocardial injury. This study demonstrates that excess myocardial accumulation of 99m-Tc pyrophosphate can occur in patients with stable angina pectoris."}
{"id": "PMID:195453", "title": "Primary prevention of coronary heart disease: a critique.", "content": "The question is whether alteration of risk factors will aid primary and secondary prevention of coronary heart disease. Critical review of available evidence indicates that inferences have been made about the beneficial effects of risk factor modification without an adequate test of the hypothesis. Trial interventions to assess the efficacy of serum cholesterol-lowering measures have had negative or equivocal results. It remains to be seen whether the findings of clinical trials on hypertension can be applied toward primary prevention of coronary heart disease in the community. The cigarette smoking habit seems to be unique among coronary heart disease risk factors. The evidence appears sufficient to justify serious consideration of a strategy of preventing the smoking habit now, persuading patients to stop and encouraging teenagers not to start.", "contents": "Primary prevention of coronary heart disease: a critique. The question is whether alteration of risk factors will aid primary and secondary prevention of coronary heart disease. Critical review of available evidence indicates that inferences have been made about the beneficial effects of risk factor modification without an adequate test of the hypothesis. Trial interventions to assess the efficacy of serum cholesterol-lowering measures have had negative or equivocal results. It remains to be seen whether the findings of clinical trials on hypertension can be applied toward primary prevention of coronary heart disease in the community. The cigarette smoking habit seems to be unique among coronary heart disease risk factors. The evidence appears sufficient to justify serious consideration of a strategy of preventing the smoking habit now, persuading patients to stop and encouraging teenagers not to start."}
{"id": "PMID:195454", "title": "Collaborative US-USSR study on the prevalence of dyslipoproteinemias and ischemic heart disease in American and Soviet populations. Prepared by the US-USSR Steering Committee for Problem Area 1: the pathogenesis of atherosclerosis.", "content": "The ongoing collaborative US-USSR study of the prevalence of dyslipoproteinemias, based on the Lipid Research Clinics Study protocol, is described. The purpose of this multidisciplinary, multiclinic program is to investigate the relation of plasma lipids and lipoproteins and other risk factors to atherosclerotic disease in selected populations. The research design, sampling strategy and general hypotheses of the study are detailed. Common quality control methods and standardized screening procedures used in data collection are reviewed. Components of the study include measurement of plasma lipids and lipoproteins, the collection of demographic and physiologic information, a 24-hour dietary recall, administration of the Rose questionnaire and resting and exercise electrocardiograms. Preliminary comparative data for total plasma cholesterol, triglycerides and high density lipoprotein cholesterol are presented for men aged 40 to 59 years.", "contents": "Collaborative US-USSR study on the prevalence of dyslipoproteinemias and ischemic heart disease in American and Soviet populations. Prepared by the US-USSR Steering Committee for Problem Area 1: the pathogenesis of atherosclerosis. The ongoing collaborative US-USSR study of the prevalence of dyslipoproteinemias, based on the Lipid Research Clinics Study protocol, is described. The purpose of this multidisciplinary, multiclinic program is to investigate the relation of plasma lipids and lipoproteins and other risk factors to atherosclerotic disease in selected populations. The research design, sampling strategy and general hypotheses of the study are detailed. Common quality control methods and standardized screening procedures used in data collection are reviewed. Components of the study include measurement of plasma lipids and lipoproteins, the collection of demographic and physiologic information, a 24-hour dietary recall, administration of the Rose questionnaire and resting and exercise electrocardiograms. Preliminary comparative data for total plasma cholesterol, triglycerides and high density lipoprotein cholesterol are presented for men aged 40 to 59 years."}
{"id": "PMID:195455", "title": "Components of 25-hydroxyvitamin D in serum of young children in upper midwestern United States.", "content": "The relative importance of cholecalciferof (vitamin D3) and ergocalciferol (vitamin D2) in maintaining the vitamin D level in children (1/2 to 6 years old) living in the upper midwestern United States was determined by measurement of total 25-hydroxyvitamin D (25-OH-D), its components, and other indices of calcium homeostasis in serum. In 38 normal children, mean (range) serum total 25-OH-D was 32.8 (less than 5 to 53) ng/ml; in 25 of the 28 sera partitioned, the major component was 25-OH-D3. Significant seasonal variation in serum 25-OH-D3 (mean, range: 35.2, 17 to 51 ng/ml in summer and 15.9, less than 5 to 32 ng/ml in winter) was not accompanied by changes in mean serum 25-OH-D2, calcium, phosphorus, or alkaline phosphatase values. However, individual serum total 25-OH-D values correlated with serum phosphorus values (r = 0.37; P less than 0.05). The proportion of the total represented by 25-OH-D3 varied widely, with a a mean of 83% in summer and 67% in winter. Sources of D3, which include both dermal synthesis and intestinal absorption of D3 added to milk, appear to be more important than sources of D2 in maintaining vitamin D nutrition of young children throughout the year. However, sources of D2 offset the decrease in total 25-OH-D in winter months.", "contents": "Components of 25-hydroxyvitamin D in serum of young children in upper midwestern United States. The relative importance of cholecalciferof (vitamin D3) and ergocalciferol (vitamin D2) in maintaining the vitamin D level in children (1/2 to 6 years old) living in the upper midwestern United States was determined by measurement of total 25-hydroxyvitamin D (25-OH-D), its components, and other indices of calcium homeostasis in serum. In 38 normal children, mean (range) serum total 25-OH-D was 32.8 (less than 5 to 53) ng/ml; in 25 of the 28 sera partitioned, the major component was 25-OH-D3. Significant seasonal variation in serum 25-OH-D3 (mean, range: 35.2, 17 to 51 ng/ml in summer and 15.9, less than 5 to 32 ng/ml in winter) was not accompanied by changes in mean serum 25-OH-D2, calcium, phosphorus, or alkaline phosphatase values. However, individual serum total 25-OH-D values correlated with serum phosphorus values (r = 0.37; P less than 0.05). The proportion of the total represented by 25-OH-D3 varied widely, with a a mean of 83% in summer and 67% in winter. Sources of D3, which include both dermal synthesis and intestinal absorption of D3 added to milk, appear to be more important than sources of D2 in maintaining vitamin D nutrition of young children throughout the year. However, sources of D2 offset the decrease in total 25-OH-D in winter months."}
{"id": "PMID:195456", "title": "Intranasal mixed tumors (pleomorphic adenomas): a clinicopathologic study of 40 cases.", "content": "The clinical, gross, and microscopic features of 40 cases of intranasal mixed tumor (pleomorphic adenoma) are reviewed and studied. The majority of these neoplasms originate from the mucosa of the bony or cartilaginous septum; they also occur on the lateral nasal wall. They may be found at any age, but the majority of our cases occurred in persons in the third through sixth decades of life. There was no significant sex predilection. All patients whose race was recorded (35) were Caucasian. The patients commonly had symptoms of nasal obstruction or the presence of a mass in the nasal cavity, or both. Clinically, the lesions were not unique, frequently being described only as polypoid, broad-based swellings. Microscopically, although similar to mixed tumors of major salivary glands, these tumors differed by being highly cellular (epithelial), with little or no stromal component, and thus simulated more aggressive epithelial neoplasms. Follow-up data (mean 7.5 years) in 34 of the 40 cases showed no evidence to suggest aggressive behavior. Thirty-one of the 34 cases followed showed no recurrence, regardless of the type of excisional procedure used. Those that did recur were either persistent from inadequate primary excisions (2 cases) or recurred locally (1) and were removed without sequelae. Local but adequate excision appears to be the treatment of choice.", "contents": "Intranasal mixed tumors (pleomorphic adenomas): a clinicopathologic study of 40 cases. The clinical, gross, and microscopic features of 40 cases of intranasal mixed tumor (pleomorphic adenoma) are reviewed and studied. The majority of these neoplasms originate from the mucosa of the bony or cartilaginous septum; they also occur on the lateral nasal wall. They may be found at any age, but the majority of our cases occurred in persons in the third through sixth decades of life. There was no significant sex predilection. All patients whose race was recorded (35) were Caucasian. The patients commonly had symptoms of nasal obstruction or the presence of a mass in the nasal cavity, or both. Clinically, the lesions were not unique, frequently being described only as polypoid, broad-based swellings. Microscopically, although similar to mixed tumors of major salivary glands, these tumors differed by being highly cellular (epithelial), with little or no stromal component, and thus simulated more aggressive epithelial neoplasms. Follow-up data (mean 7.5 years) in 34 of the 40 cases showed no evidence to suggest aggressive behavior. Thirty-one of the 34 cases followed showed no recurrence, regardless of the type of excisional procedure used. Those that did recur were either persistent from inadequate primary excisions (2 cases) or recurred locally (1) and were removed without sequelae. Local but adequate excision appears to be the treatment of choice."}
{"id": "PMID:195458", "title": "Sensitive fluorimetric assay for serum angiotensin-converting enzyme with the natural substrate angiotensin I.", "content": "A simple, rapid, highly sensitive and reproducible fluorimetric assay for angiotensin-converting enzyme in untreated serum using the natural substrate based on a similar assay with hippuryl-L-histidine-L-leucine is described. Angiotensin I (0.2 mM in 0.1 M potassium phosphate-30 mM NaCl, pH 7.5; 37 C) is converted to angiotensin II and L-histidyl-L-leucine, which is quantified fluorimetrically (excitation = 360 nm; fluorescence, 500 nm) by formation of a fluorescent adduct with O-phthaldialdehyde. L-Histidyl-L-leucine peptidase was also monitored in order to correct for significant activity, which was observed only once, in less than 1% sera. The mean value of serum angiotensin-converting enzyme in sera from 45 normal subjects was 4.69+/-0.194 (SEM)+/-1.30 (SD) nmol/min/ml serum, compared with 31.7+/-1.53 (SEM)+/-10.3(SD) with the substrate analog hippuryl-L-histidine-L-leucine. There was a high degree of correlation between the velocity of cleavage of angiotensin I and hippuryl-L-histidyl-L-leucine (r - 0.903 to 0.993). The assay of serum angiotensin-converting enzyme is of use in the diagnosis and possible management of sarcoidosis and Gaucher's disease, and may have other applications.", "contents": "Sensitive fluorimetric assay for serum angiotensin-converting enzyme with the natural substrate angiotensin I. A simple, rapid, highly sensitive and reproducible fluorimetric assay for angiotensin-converting enzyme in untreated serum using the natural substrate based on a similar assay with hippuryl-L-histidine-L-leucine is described. Angiotensin I (0.2 mM in 0.1 M potassium phosphate-30 mM NaCl, pH 7.5; 37 C) is converted to angiotensin II and L-histidyl-L-leucine, which is quantified fluorimetrically (excitation = 360 nm; fluorescence, 500 nm) by formation of a fluorescent adduct with O-phthaldialdehyde. L-Histidyl-L-leucine peptidase was also monitored in order to correct for significant activity, which was observed only once, in less than 1% sera. The mean value of serum angiotensin-converting enzyme in sera from 45 normal subjects was 4.69+/-0.194 (SEM)+/-1.30 (SD) nmol/min/ml serum, compared with 31.7+/-1.53 (SEM)+/-10.3(SD) with the substrate analog hippuryl-L-histidine-L-leucine. There was a high degree of correlation between the velocity of cleavage of angiotensin I and hippuryl-L-histidyl-L-leucine (r - 0.903 to 0.993). The assay of serum angiotensin-converting enzyme is of use in the diagnosis and possible management of sarcoidosis and Gaucher's disease, and may have other applications."}
{"id": "PMID:195459", "title": "Comparison of primary rhesus and cynomolgus monkey kidney cell cultures for viral isolation from clinical specimens.", "content": "Rhesus monkey kidney and cynomolgus monkey kidney cell cultures were compared for viral isolation by using clinical specimens that yielded 203 viral isolates. Cynomolgus and rhesus monkey kidney cells were comparable for the isolation of 22 adenoviruses, 12 coxsackieviruses, and one poliovirus. Four of 50 echoviruses and seven of ten herpesviruses were detected only in cynomolgus monkey kidney cells. Influenza virus was isolated in 84 instances, of which eight were detected only in rhesus and four only in cynomolgus monkey kidney cells. Rhesus monkey kidney cells yielded six more parainfluenza virus isolates. Except possibly for parainfluenza virus, cynomolgus monkey kidney cells appear to be as sensitive as rhesus monkey kidney cells for viral isolation from clinical specimens.", "contents": "Comparison of primary rhesus and cynomolgus monkey kidney cell cultures for viral isolation from clinical specimens. Rhesus monkey kidney and cynomolgus monkey kidney cell cultures were compared for viral isolation by using clinical specimens that yielded 203 viral isolates. Cynomolgus and rhesus monkey kidney cells were comparable for the isolation of 22 adenoviruses, 12 coxsackieviruses, and one poliovirus. Four of 50 echoviruses and seven of ten herpesviruses were detected only in cynomolgus monkey kidney cells. Influenza virus was isolated in 84 instances, of which eight were detected only in rhesus and four only in cynomolgus monkey kidney cells. Rhesus monkey kidney cells yielded six more parainfluenza virus isolates. Except possibly for parainfluenza virus, cynomolgus monkey kidney cells appear to be as sensitive as rhesus monkey kidney cells for viral isolation from clinical specimens."}
{"id": "PMID:195461", "title": "Viruses associated with acute gastroenteritis in young children.", "content": "Conventional virologic investigations generally failed to implicate viruses as a cause of acute gastroenteritis in young children. When negative-contrast stain electron microscopy was used for the examination of stool samples from affected patients, several candidate etiologic agents were discovered. Rotavirus (otherwise known as orbivirus, reo-like agent, and infantile gastroenteritis virus) emerged as an important causative agent. In a considerable number of patients, however, no causative agent was identified. Several other candidate etiologic viruses now \"stand in the wings\" awaiting additional evidence as to their role in the pathogenesis of acute gastroenteritis. In a study period of 12 months, 669 patients were found to be shedding virus in association with symptoms of diarrhea, vomiting, and temperature elevation. Approximately one third of these patients acquired their infection in hospital.", "contents": "Viruses associated with acute gastroenteritis in young children. Conventional virologic investigations generally failed to implicate viruses as a cause of acute gastroenteritis in young children. When negative-contrast stain electron microscopy was used for the examination of stool samples from affected patients, several candidate etiologic agents were discovered. Rotavirus (otherwise known as orbivirus, reo-like agent, and infantile gastroenteritis virus) emerged as an important causative agent. In a considerable number of patients, however, no causative agent was identified. Several other candidate etiologic viruses now \"stand in the wings\" awaiting additional evidence as to their role in the pathogenesis of acute gastroenteritis. In a study period of 12 months, 669 patients were found to be shedding virus in association with symptoms of diarrhea, vomiting, and temperature elevation. Approximately one third of these patients acquired their infection in hospital."}
{"id": "PMID:195462", "title": "Clinical manifestations of renal allograft derived primary cytomegalovirus infection.", "content": "Seventy seven patients, thirteen younger than 20 years of age, were followed up prospectively for the first three months after renal transplant for evidence of infection and illness due to cytomegalovirus (CMV). Thirty-two developed reactivation of latent CMV and 29 did not develop any CMV infection and wn, five had pneumonia, and four underwent nephrectomy. Of these, 16, eleven received a kidney from a parent, whereas of the other 61 patients, five received parental kidneys (P less than .001). Hence, CMV seronegative individuals who received a kidney from a CMV seropositive parent developed clinical illness and sometimes lost the allograft.", "contents": "Clinical manifestations of renal allograft derived primary cytomegalovirus infection. Seventy seven patients, thirteen younger than 20 years of age, were followed up prospectively for the first three months after renal transplant for evidence of infection and illness due to cytomegalovirus (CMV). Thirty-two developed reactivation of latent CMV and 29 did not develop any CMV infection and wn, five had pneumonia, and four underwent nephrectomy. Of these, 16, eleven received a kidney from a parent, whereas of the other 61 patients, five received parental kidneys (P less than .001). Hence, CMV seronegative individuals who received a kidney from a CMV seropositive parent developed clinical illness and sometimes lost the allograft."}
{"id": "PMID:195463", "title": "Plasma 25-hydroxyvitamin D and urinary cyclic AMP in German patients with subtotal gastrectomy (Billroth II).", "content": "In an attempt to clarify the pathogenesis of the disturbed calcium metabolism which sometimes follows partial gastrectomy, we determined plasma 25-hydroxyvitamin D (25-OH-D) concentrations and urinary cyclic 3',5'-adenosine monophosphate (cAMP) excretion in patients who had previously undergone Billroth II gastrectomy and who were without clinical evidence of bone disease. In 17 Billroth II patients plasma 25-OH-D concentrations were reduced (12.6 +/- 4.6 ng/ml, mean +/- SD) compared to values in 17 control patients with diseases not affecting calcium metabolism (31.6 +/- 12.9 ng/ml, P less than 0.001). Urinary cAMP excretion, in part reflecting parathyroid function, was higher in 17 Billroth II patients (5.0 +/- 2.5 micronmol/day) than in the control patients (2.6 +/- 1.3 micronmol/day, P less than 0.001). These results suggest impaired nutrition of vitamin D and secondary hyperparathyroidism in Billroth II patients. While the cause of this phenomenon is unclear, it may contribute to the disturbance of calcium metabolism in patients who have had subtotal gastrectomy.", "contents": "Plasma 25-hydroxyvitamin D and urinary cyclic AMP in German patients with subtotal gastrectomy (Billroth II). In an attempt to clarify the pathogenesis of the disturbed calcium metabolism which sometimes follows partial gastrectomy, we determined plasma 25-hydroxyvitamin D (25-OH-D) concentrations and urinary cyclic 3',5'-adenosine monophosphate (cAMP) excretion in patients who had previously undergone Billroth II gastrectomy and who were without clinical evidence of bone disease. In 17 Billroth II patients plasma 25-OH-D concentrations were reduced (12.6 +/- 4.6 ng/ml, mean +/- SD) compared to values in 17 control patients with diseases not affecting calcium metabolism (31.6 +/- 12.9 ng/ml, P less than 0.001). Urinary cAMP excretion, in part reflecting parathyroid function, was higher in 17 Billroth II patients (5.0 +/- 2.5 micronmol/day) than in the control patients (2.6 +/- 1.3 micronmol/day, P less than 0.001). These results suggest impaired nutrition of vitamin D and secondary hyperparathyroidism in Billroth II patients. While the cause of this phenomenon is unclear, it may contribute to the disturbance of calcium metabolism in patients who have had subtotal gastrectomy."}
{"id": "PMID:195465", "title": "Cyclic adenosine monophosphate and human gastric acid secretion.", "content": "This report concerns gastric juice, plasma, and urinary levels of adenosine 3',5'-monophosphate (cAMP) in 27 subjects undergoing routine gastric analysis under maximum stimulation with betazole or pentagastrin. Cyclic AMP was measured by sensitive and specific radioimmunoassay. No increase in concentration of cAMP was noted in gastric juice, plasma, or urine following either betazole or pentagastrin stimulation. Betazole-stimulated human gastric acid secretion was associated with an increased cAMP output into the gastric juice (P less than 0.05). There was no change in cAMP output following pentagastrin stimulation. The peak acid output produced by pentagastrin and betazole was similar. The lack of increase in cAMP concentration lends support to the concept that cyclic AMP is not a primary mediator in the stimulation of gastric acid secretion by betazole or pentagastrin in the human. The physiologic significance of the increase in cAMP output following betazole stimulation remains unresolved.", "contents": "Cyclic adenosine monophosphate and human gastric acid secretion. This report concerns gastric juice, plasma, and urinary levels of adenosine 3',5'-monophosphate (cAMP) in 27 subjects undergoing routine gastric analysis under maximum stimulation with betazole or pentagastrin. Cyclic AMP was measured by sensitive and specific radioimmunoassay. No increase in concentration of cAMP was noted in gastric juice, plasma, or urine following either betazole or pentagastrin stimulation. Betazole-stimulated human gastric acid secretion was associated with an increased cAMP output into the gastric juice (P less than 0.05). There was no change in cAMP output following pentagastrin stimulation. The peak acid output produced by pentagastrin and betazole was similar. The lack of increase in cAMP concentration lends support to the concept that cyclic AMP is not a primary mediator in the stimulation of gastric acid secretion by betazole or pentagastrin in the human. The physiologic significance of the increase in cAMP output following betazole stimulation remains unresolved."}
{"id": "PMID:195466", "title": "Genetic complementation of propionyl-CoA carboxylase deficiency in cultured human fibroblasts.", "content": "Propionyl-CoA carboxylase (PCC) deficiency is an inherited metabolic disorder showing considerable variability of expression. We have investigated the possibility that there is a genetic basis for the clinical heterogeneity in this disorder by examining complementation in Sendai virus mediated heterokaryons of mutant fibroblast strains. Restoration of PCC activity was monitored in individual multinucleate cells in situ using a radioautographic procedure which detects the incorporation of 14C-propionate into trichloracetic acid precipitable material. Each mutant strain incorporated negligible amounts of radioactivity compared to control strains. Activity was not restored when different mutants were mixed without virus or when homokaryons were produced by self-fusion. Seven mutant strains were fused in all pairwise combinations and examined for increased 14C-propionate incorporation in heterokaryons. Two main complementation groups were revealed. One group was composed of three mutants. The other was a complex group composed of four mutants in which intragroup complementation was demonstrated. Two mutants showing excellent complementation by radioautography were examined for complementation by the direct assay of PCC ACTIVITY. The enzyme activity of virus-treated preparations with 23% multinucleate cells was 183 U (pmol/min/mg protein) compared to 16 U for the untreated mixture (normal range 450-850 u). We conclude that PCC deficiency resulted from mutations of heterogeneous origin, although the classification of mutants into complementation groups did not correlate with patterns of clinical heterogeneity.", "contents": "Genetic complementation of propionyl-CoA carboxylase deficiency in cultured human fibroblasts. Propionyl-CoA carboxylase (PCC) deficiency is an inherited metabolic disorder showing considerable variability of expression. We have investigated the possibility that there is a genetic basis for the clinical heterogeneity in this disorder by examining complementation in Sendai virus mediated heterokaryons of mutant fibroblast strains. Restoration of PCC activity was monitored in individual multinucleate cells in situ using a radioautographic procedure which detects the incorporation of 14C-propionate into trichloracetic acid precipitable material. Each mutant strain incorporated negligible amounts of radioactivity compared to control strains. Activity was not restored when different mutants were mixed without virus or when homokaryons were produced by self-fusion. Seven mutant strains were fused in all pairwise combinations and examined for increased 14C-propionate incorporation in heterokaryons. Two main complementation groups were revealed. One group was composed of three mutants. The other was a complex group composed of four mutants in which intragroup complementation was demonstrated. Two mutants showing excellent complementation by radioautography were examined for complementation by the direct assay of PCC ACTIVITY. The enzyme activity of virus-treated preparations with 23% multinucleate cells was 183 U (pmol/min/mg protein) compared to 16 U for the untreated mixture (normal range 450-850 u). We conclude that PCC deficiency resulted from mutations of heterogeneous origin, although the classification of mutants into complementation groups did not correlate with patterns of clinical heterogeneity."}
{"id": "PMID:195467", "title": "Human red cell 2,3-diphosphoglycerate mutase and monophosphoglycerate mutase: genetic evidence for two separate loci.", "content": "Rare genetic variants of human red cell 2,3-diphosphoglycerate mutase (DPGM) and monophosphoglycerate mutase (MPGM) were compared by starch gel electrophoresis. The isozyme patterns showed that genetic variation of the enzymes were independent from each other, thus DPGM and MPGM must be controlled by two separate loci.", "contents": "Human red cell 2,3-diphosphoglycerate mutase and monophosphoglycerate mutase: genetic evidence for two separate loci. Rare genetic variants of human red cell 2,3-diphosphoglycerate mutase (DPGM) and monophosphoglycerate mutase (MPGM) were compared by starch gel electrophoresis. The isozyme patterns showed that genetic variation of the enzymes were independent from each other, thus DPGM and MPGM must be controlled by two separate loci."}
{"id": "PMID:195470", "title": "Pathogenesis of the slow disease of the central nervous system associated with WM 1504 E virus. I. Relationship of strain susceptibility and replication to disease.", "content": "Inbred mouse strains vary considerably in their susceptibility to the chronic neurologic disease caused by WM 1504 E virus. Although all strains inoculated with the virus showed evidence of viral replication, those strains destined to develop chronic disease showed consistently higher titers of viral antigen in their sera and also in their tissues, particularly in the central nervous system, than did resistant strains. Studies of hybrids made by mating susceptible C57BR/cdJ and resistant C57BL/6J strains indicated that resistance is dominant and not sex linked. The major areas of injury included neurons in the anterior horn of the spinal cord, the dentate nucleus of the cerebellum, and other nuclei in the brain stem. Involvement of oligodendrocytes with associated primary demyelination was also noted. Tissue damage accompanied intense gliosis but was without leukocyte infiltration. Immunopathologic studies and parabiotic experiments suggested that tissue injury was likely due to primary direct viral effects. Further, thymus-insufficient nude mice developed this chronic neurologic disease.", "contents": "Pathogenesis of the slow disease of the central nervous system associated with WM 1504 E virus. I. Relationship of strain susceptibility and replication to disease. Inbred mouse strains vary considerably in their susceptibility to the chronic neurologic disease caused by WM 1504 E virus. Although all strains inoculated with the virus showed evidence of viral replication, those strains destined to develop chronic disease showed consistently higher titers of viral antigen in their sera and also in their tissues, particularly in the central nervous system, than did resistant strains. Studies of hybrids made by mating susceptible C57BR/cdJ and resistant C57BL/6J strains indicated that resistance is dominant and not sex linked. The major areas of injury included neurons in the anterior horn of the spinal cord, the dentate nucleus of the cerebellum, and other nuclei in the brain stem. Involvement of oligodendrocytes with associated primary demyelination was also noted. Tissue damage accompanied intense gliosis but was without leukocyte infiltration. Immunopathologic studies and parabiotic experiments suggested that tissue injury was likely due to primary direct viral effects. Further, thymus-insufficient nude mice developed this chronic neurologic disease."}
{"id": "PMID:195471", "title": "Surface morphology of normal and neoplastic rat cells.", "content": "Nontumorigenic rat cells and their tumorigenic counterparts were studied with scanning electron microscopy under controlled conditions in vitro and with transmission electron microscopy after replantation in vivo to discern if external morphology reflected the cell's neoplastic state or the etiology of transformation. Interphase cells in six of seven nontumorigenic lines were flat and monolayered under confluent conditions and exhibited smooth, nonactive cell surfaces. A nontumorigenic cell line morphologically transformed with human adenovirus-2 consisted of spherical cells with blebbed surfaces. Cells from six tumorigenic lines transformed with avian sarcoma virus had highly active surfaces with many surface projections. Cells from two chemical carcinogen-transformed rat embryo lines were flat with no surface projections in subconfluent culture and rounded with only a few microvilli at high densities, but cells from a sarcoma chemically induced in an adult rat were villous. When villous cells were syngeneically replanted in vivo, they lost most microvilli. The external morphology of cells was influenced by a number of factors simultaneously, with no universal pattern associated with tumorigenic capacity or transforming agent.", "contents": "Surface morphology of normal and neoplastic rat cells. Nontumorigenic rat cells and their tumorigenic counterparts were studied with scanning electron microscopy under controlled conditions in vitro and with transmission electron microscopy after replantation in vivo to discern if external morphology reflected the cell's neoplastic state or the etiology of transformation. Interphase cells in six of seven nontumorigenic lines were flat and monolayered under confluent conditions and exhibited smooth, nonactive cell surfaces. A nontumorigenic cell line morphologically transformed with human adenovirus-2 consisted of spherical cells with blebbed surfaces. Cells from six tumorigenic lines transformed with avian sarcoma virus had highly active surfaces with many surface projections. Cells from two chemical carcinogen-transformed rat embryo lines were flat with no surface projections in subconfluent culture and rounded with only a few microvilli at high densities, but cells from a sarcoma chemically induced in an adult rat were villous. When villous cells were syngeneically replanted in vivo, they lost most microvilli. The external morphology of cells was influenced by a number of factors simultaneously, with no universal pattern associated with tumorigenic capacity or transforming agent."}
{"id": "PMID:195472", "title": "Early lesions of pancreatic ductal carcinoma in the hamster model.", "content": "Syrian golden hamsters were treated weekly with 10 mg/kg body weight N-nitrosobis (2-oxopropyl) amine for life (Group 1) or 6 weeks and were sacrificed at biweekly intervals from 2 weeks (Group 1) and 8 weeks (Group 2) after initiation of the experiment. The pancreas was examined in step sections, and the sequential alterations noted for each interval were recorded. Lesions were found in intrapancreatic and extrapancreatic ducts. Equivalent alterations consisting of hyperplasia, metaplasia, atypia, and lesions characteristic of carcinoma in situ developed ubiquitously and simultaneously in pancreatic ducts of different sizes and in ductules, but not in acinar cells. Among the most significant findings were intrainsular ductular formations, their proliferation, and sequential malignant alteration comparable to the involved preexisting ductules. Differences between the two experimental groups were of a quantitative rather than qualitative nature. The incidence and multiplicity of neoplastic lesions at each interval according to group, sex, and anatomic locations of adenocarcinomas are outlined. Predilected areas for some lesions were found. Results indicate a common origin of all induced tumors from a pluripotent cell populating the pancreatic ductal system.", "contents": "Early lesions of pancreatic ductal carcinoma in the hamster model. Syrian golden hamsters were treated weekly with 10 mg/kg body weight N-nitrosobis (2-oxopropyl) amine for life (Group 1) or 6 weeks and were sacrificed at biweekly intervals from 2 weeks (Group 1) and 8 weeks (Group 2) after initiation of the experiment. The pancreas was examined in step sections, and the sequential alterations noted for each interval were recorded. Lesions were found in intrapancreatic and extrapancreatic ducts. Equivalent alterations consisting of hyperplasia, metaplasia, atypia, and lesions characteristic of carcinoma in situ developed ubiquitously and simultaneously in pancreatic ducts of different sizes and in ductules, but not in acinar cells. Among the most significant findings were intrainsular ductular formations, their proliferation, and sequential malignant alteration comparable to the involved preexisting ductules. Differences between the two experimental groups were of a quantitative rather than qualitative nature. The incidence and multiplicity of neoplastic lesions at each interval according to group, sex, and anatomic locations of adenocarcinomas are outlined. Predilected areas for some lesions were found. Results indicate a common origin of all induced tumors from a pluripotent cell populating the pancreatic ductal system."}
{"id": "PMID:195473", "title": "Somatostatin-immunoreactive cells in medullary carcinoma of the thyroid.", "content": "Ten medullary carcinomas of the thyroid were examined by immunohistochemistry using antisera against calcitonin, somatostatin, and ACTH. In addition to calcitonin cells, eight of the tumors contained somatostatin-immunoreactive cells in varying numbers. No ACTH-immunoreactive cells were found. The results indicate that thyroid medullary carcinomas often are multihormonal, and that somatostatin is common in such tumors. In contrast to calcitonin cells, somatostatin cells are not found in normal human thyroid tissue.", "contents": "Somatostatin-immunoreactive cells in medullary carcinoma of the thyroid. Ten medullary carcinomas of the thyroid were examined by immunohistochemistry using antisera against calcitonin, somatostatin, and ACTH. In addition to calcitonin cells, eight of the tumors contained somatostatin-immunoreactive cells in varying numbers. No ACTH-immunoreactive cells were found. The results indicate that thyroid medullary carcinomas often are multihormonal, and that somatostatin is common in such tumors. In contrast to calcitonin cells, somatostatin cells are not found in normal human thyroid tissue."}
{"id": "PMID:195475", "title": "Calcium dependence of neuromuscular events in esophageal smooth muscle of the opossum.", "content": "Intramural nerves in smooth muscle strips from opossum esophagus were stimulated electrically to cause contractions of longitudinal body muscle, off responses of transverse body muscle and relaxations of sphincter muscle. Krebs solution was modified by calcium removal by strontium substitution for calcium, by adding magnesium, and by adding nitroprusside. Longitudinal muscle contractions were abolished by calcium removal and by excess magnesium; they were unaffected by nitroprusside; strontium could not replace calcium. Off responses were abolished by calcium removal and by excess magnesium; they were depressed by nitroprusside; strontium effectively replaced calcium. Resting active tension in sphincter strips was partly reduced by calcium removal and by excess magnesium; it was abolished by nitroprusside; strontium could not replace calcium. Relaxations in sphincter strips were unaffected by all experimental conditions. Longitudinal contractions, off responses, and resting active tension of the sphincter represent different kinds of calcium activation of muscle. The excitatory nerves (which are cholinergic) in longitudinal muscle are calcium dependent, the nerves that produce off responses may not be, and the nerves that relax the sphincter are not.", "contents": "Calcium dependence of neuromuscular events in esophageal smooth muscle of the opossum. Intramural nerves in smooth muscle strips from opossum esophagus were stimulated electrically to cause contractions of longitudinal body muscle, off responses of transverse body muscle and relaxations of sphincter muscle. Krebs solution was modified by calcium removal by strontium substitution for calcium, by adding magnesium, and by adding nitroprusside. Longitudinal muscle contractions were abolished by calcium removal and by excess magnesium; they were unaffected by nitroprusside; strontium could not replace calcium. Off responses were abolished by calcium removal and by excess magnesium; they were depressed by nitroprusside; strontium effectively replaced calcium. Resting active tension in sphincter strips was partly reduced by calcium removal and by excess magnesium; it was abolished by nitroprusside; strontium could not replace calcium. Relaxations in sphincter strips were unaffected by all experimental conditions. Longitudinal contractions, off responses, and resting active tension of the sphincter represent different kinds of calcium activation of muscle. The excitatory nerves (which are cholinergic) in longitudinal muscle are calcium dependent, the nerves that produce off responses may not be, and the nerves that relax the sphincter are not."}
{"id": "PMID:195477", "title": "Fibrinogen synthesis stimulation by prostaglandin E1 and some other vasodilators.", "content": "Three-hour constant-rate intravenous infusion into rabbits of 1-3 mg prostaglandin E1 (PGE1) per kilogram markedly increased plasma fibrinogen 24 h later. 131I-labeled fibrinogen and model studies showed increased synthesis underlay this. Similar PGE1 doses lowered systolic blood pressure. Maintaining systolic blood pressure by infusing noradrenaline with the PGE1 did not alter plasma fibrinogen response to PGE1; plasma fibrinogen was unchanged by noradrenaline infusion. Regression equations relating plasma fibrinogen increment to PGE1 dose, plasma fibrinogen increment to dose and systolic blood pressure change, and systolic blood pressure change to dose are given as well as the constants relating plasma fibrinogen increment to dose using the Michaelis-Menten equation. Infusions of cyclic AMP, dibutyryl cyclic AMP, and cyclic GMP intravenously led to only small plasma fibrinogen increases. Daily intravenous infusions of PGE1 led to loss of both plasma fibrinogen and systolic blood pressure responses in two animals; a third animal showed only loss of the former and a fourth only loss of the latter response. PGE1 slightly enhanced the small plasma fibrinogen increase following intravenous bradykinin. Approximate arterial blood PGE1 concentrations resulting from the intravenous infusion of 1 mg mg PGE1 kg-1 3 h-1 are calculated. These are compared with measured values.", "contents": "Fibrinogen synthesis stimulation by prostaglandin E1 and some other vasodilators. Three-hour constant-rate intravenous infusion into rabbits of 1-3 mg prostaglandin E1 (PGE1) per kilogram markedly increased plasma fibrinogen 24 h later. 131I-labeled fibrinogen and model studies showed increased synthesis underlay this. Similar PGE1 doses lowered systolic blood pressure. Maintaining systolic blood pressure by infusing noradrenaline with the PGE1 did not alter plasma fibrinogen response to PGE1; plasma fibrinogen was unchanged by noradrenaline infusion. Regression equations relating plasma fibrinogen increment to PGE1 dose, plasma fibrinogen increment to dose and systolic blood pressure change, and systolic blood pressure change to dose are given as well as the constants relating plasma fibrinogen increment to dose using the Michaelis-Menten equation. Infusions of cyclic AMP, dibutyryl cyclic AMP, and cyclic GMP intravenously led to only small plasma fibrinogen increases. Daily intravenous infusions of PGE1 led to loss of both plasma fibrinogen and systolic blood pressure responses in two animals; a third animal showed only loss of the former and a fourth only loss of the latter response. PGE1 slightly enhanced the small plasma fibrinogen increase following intravenous bradykinin. Approximate arterial blood PGE1 concentrations resulting from the intravenous infusion of 1 mg mg PGE1 kg-1 3 h-1 are calculated. These are compared with measured values."}
{"id": "PMID:195478", "title": "Action of adenosine and adenine nucleotides on dogs' isolated veins.", "content": "Adenosine depressed norepinephrine contractions of dogs' saphenous vein strips in both the presence and the absence of Ca2+ and after inhibition of calcium influx by verapamil. It antagonized noncompetitively contractions induced by Ca2+ in depolarized strips after alpha-adrenergic blockade. Contractions obtained with acetylcholine were also depressed by adenosine. This depression was not accompanied by an increase in cAMP or a decrease in the elevated cGMP level. Thus the depression of the smooth muscle cell reactivity still occurs in the absence of calcium influx and is not mediated by the cyclic 3',5'-nucleotide system. Adenosine diphosphate and triphosphate, but not adenosine (10(-6) to 10(-4) M), increased the basal tension of resting saphenous strips. This was prevented by removal of calcium from the bath. In contracted strips, lower concentrations of both nucleotides (10(-6) to 10(-5) M) caused relaxation whereas with high concentrations (10(-4) to 10(-3) M) further contraction occurred. Thus, unlike adenosine, the adenine nucleotides facilitate calcium influx.", "contents": "Action of adenosine and adenine nucleotides on dogs' isolated veins. Adenosine depressed norepinephrine contractions of dogs' saphenous vein strips in both the presence and the absence of Ca2+ and after inhibition of calcium influx by verapamil. It antagonized noncompetitively contractions induced by Ca2+ in depolarized strips after alpha-adrenergic blockade. Contractions obtained with acetylcholine were also depressed by adenosine. This depression was not accompanied by an increase in cAMP or a decrease in the elevated cGMP level. Thus the depression of the smooth muscle cell reactivity still occurs in the absence of calcium influx and is not mediated by the cyclic 3',5'-nucleotide system. Adenosine diphosphate and triphosphate, but not adenosine (10(-6) to 10(-4) M), increased the basal tension of resting saphenous strips. This was prevented by removal of calcium from the bath. In contracted strips, lower concentrations of both nucleotides (10(-6) to 10(-5) M) caused relaxation whereas with high concentrations (10(-4) to 10(-3) M) further contraction occurred. Thus, unlike adenosine, the adenine nucleotides facilitate calcium influx."}
{"id": "PMID:195479", "title": "Renin-angiotensin-aldosterone system of the normothermic marmot.", "content": "Adrenal steroid secretion rates and the renin-angiotensin-aldosterone (RAA) system were studied in the normothermic marmot. Adrenal secretion by the anesthetized, laparotomized marmot was (mean +/- SEM); aldosterone 1.2 +/- 0.3 ng/min, deoxycorticosterone 16.7 +/- 11.5 ng/min, corticosterone 15.2 +/- 7.8 ng/min, and cortisol 554 +/- 108 ng/min. Four forcings were investigated that affect feedback control at different sites: adrenocorticotropic hormone (ACTH) and angiotensin II (AII) infusion, sodium (Na) depletion, and Na loading. Plasma aldosterone, cortisol, Na, and potassium (K) concentrations as well as plasma renin activity (PRA) hematocrit (Hct), and in some studies, blood pressure were measured. ACTH infusion increased the plasma concentrations of aldosterone and cortisol. AII infusion increased aldosterone concentration, blood pressure, and Hct. Na depletion increased aldosterone, Hct, and PRA; plasma Na and K were decreased. Aldosterone concentration, Hct, and PRA decreased after salt loading. Normothermic, salt-depleted marmots demonstrated a pronounced fall in blood pressure following infusion of the AII analog, 1-sarcosine-8-alanine AII. The average plasma values for aldosterone, PRA, and cortisol found in 44 control animals were: aldosterone 3.8 +/- 0.3 ng/100 ml, PRA 1.9 +/- 0.2 ng AI-ml-1-h-1, and cortisol 54 +/- 4 ng/ml. It was concluded that normothermic marmots have a RAA system comparable to other mammalian species.", "contents": "Renin-angiotensin-aldosterone system of the normothermic marmot. Adrenal steroid secretion rates and the renin-angiotensin-aldosterone (RAA) system were studied in the normothermic marmot. Adrenal secretion by the anesthetized, laparotomized marmot was (mean +/- SEM); aldosterone 1.2 +/- 0.3 ng/min, deoxycorticosterone 16.7 +/- 11.5 ng/min, corticosterone 15.2 +/- 7.8 ng/min, and cortisol 554 +/- 108 ng/min. Four forcings were investigated that affect feedback control at different sites: adrenocorticotropic hormone (ACTH) and angiotensin II (AII) infusion, sodium (Na) depletion, and Na loading. Plasma aldosterone, cortisol, Na, and potassium (K) concentrations as well as plasma renin activity (PRA) hematocrit (Hct), and in some studies, blood pressure were measured. ACTH infusion increased the plasma concentrations of aldosterone and cortisol. AII infusion increased aldosterone concentration, blood pressure, and Hct. Na depletion increased aldosterone, Hct, and PRA; plasma Na and K were decreased. Aldosterone concentration, Hct, and PRA decreased after salt loading. Normothermic, salt-depleted marmots demonstrated a pronounced fall in blood pressure following infusion of the AII analog, 1-sarcosine-8-alanine AII. The average plasma values for aldosterone, PRA, and cortisol found in 44 control animals were: aldosterone 3.8 +/- 0.3 ng/100 ml, PRA 1.9 +/- 0.2 ng AI-ml-1-h-1, and cortisol 54 +/- 4 ng/ml. It was concluded that normothermic marmots have a RAA system comparable to other mammalian species."}
{"id": "PMID:195480", "title": "In defense of community mental health.", "content": "Initial enthusiasm for community mental health has given way to a barrage of criticism, musch of it deserved. Originated to deal with abysmal conditions in state hospitals, community mental health focused instead on primary prevention, political activism, and the mildly mentally ill. The authors propose a return to the original fundamentals, stressing that the highest priority be given to community treatment and rehabilitation of the severely mentally ill.", "contents": "In defense of community mental health. Initial enthusiasm for community mental health has given way to a barrage of criticism, musch of it deserved. Originated to deal with abysmal conditions in state hospitals, community mental health focused instead on primary prevention, political activism, and the mildly mentally ill. The authors propose a return to the original fundamentals, stressing that the highest priority be given to community treatment and rehabilitation of the severely mentally ill."}
{"id": "PMID:195485", "title": "Carcinoma of the parotid gland.", "content": "Sixty-nine patients with parotid gland cancer were studied at the Cancer Control Agency of British Columbia; half were treated successfully. Localized cancers should be treated by total parotidectomy with facial nerve preservation. Facial nerve sacrifice and radical neck dissection for metastatic lymph nodes may be required. If adequate surgery has been done, the histologic type of the tumor significantly determines the outcome. Postoperative radiation to the parotid bed in the more malignant types of tumor is advocated and appears to improve the results of treatment.", "contents": "Carcinoma of the parotid gland. Sixty-nine patients with parotid gland cancer were studied at the Cancer Control Agency of British Columbia; half were treated successfully. Localized cancers should be treated by total parotidectomy with facial nerve preservation. Facial nerve sacrifice and radical neck dissection for metastatic lymph nodes may be required. If adequate surgery has been done, the histologic type of the tumor significantly determines the outcome. Postoperative radiation to the parotid bed in the more malignant types of tumor is advocated and appears to improve the results of treatment."}
{"id": "PMID:195488", "title": "Bacterial flora of stored human donor corneas after antibiotic treatment.", "content": "In 100 out of 122 eyes obtained at autopsy, bacteria could be cultured in swabs taken from the conjunctivae. After individual storage of the excised corneas at +4 degrees C in a modified tissue culture medium containing 100 microgram/ml Gentalmicin, in 18 culture specimens there was still some growth of microorganisms. In comparison to nine other antibiotics, Gentamicin was the most effective against cultivated bacteria in a sensitivity test. However, in 25% of the specimens Ps.aeruginosa was resistant to Gentamicin. Polymyxin, to which Ps.aeruginosa was not resistant in the same test, should be used in combination with Gentamicin for antibiotic treatment of stored human donor corneas.", "contents": "Bacterial flora of stored human donor corneas after antibiotic treatment. In 100 out of 122 eyes obtained at autopsy, bacteria could be cultured in swabs taken from the conjunctivae. After individual storage of the excised corneas at +4 degrees C in a modified tissue culture medium containing 100 microgram/ml Gentalmicin, in 18 culture specimens there was still some growth of microorganisms. In comparison to nine other antibiotics, Gentamicin was the most effective against cultivated bacteria in a sensitivity test. However, in 25% of the specimens Ps.aeruginosa was resistant to Gentamicin. Polymyxin, to which Ps.aeruginosa was not resistant in the same test, should be used in combination with Gentamicin for antibiotic treatment of stored human donor corneas."}
{"id": "PMID:195489", "title": "Cutaneous bullae in coma due to poisoning. An association with deep seated ischaemic lesions of muscle.", "content": "A deeply unconscious patient may develop ischaemia in those soft tissues subjected to pressure. Pressure on the skin may give rise to blistering which is reversible. Pressure on the limbs may precipitate irreversible ischaemia of the muscles and nerves unless a fasciotomy is performed.", "contents": "Cutaneous bullae in coma due to poisoning. An association with deep seated ischaemic lesions of muscle. A deeply unconscious patient may develop ischaemia in those soft tissues subjected to pressure. Pressure on the skin may give rise to blistering which is reversible. Pressure on the limbs may precipitate irreversible ischaemia of the muscles and nerves unless a fasciotomy is performed."}
{"id": "PMID:195491", "title": "Scanning electron, light, and immunofluorescent microscopy of intestine of gnotobiotic calf infected with reovirus-like agent.", "content": "Intestinal lesions caused by a calf diarrheal reovirus-like agent were studied by scanning electron microscopy, light microscopy, and immunofluorescent microscopy in 2 gnotobiotic calves inoculated per orum. The calves were euthanatized 6 hours after the onset of diarrhea. Villi in the cranial and middle parts of the small intestine appeared shortened. In these areas, the epithelium was composed of low columnar and cuboidal cells. Villi in the caudal part of the small intestine were short. By scanning electron microscopy, the villous epithelium in the caudal part of the small intestine of both calves and the ridge epithelium in the ansa spiralis coli of 1 calf were composed of various sized cells which gave the surfaces an irregular appearance. The amount of mucopolysaccharide in the colonic epithelial cells of both calves was greatly reduced. The combined use of scanning electron and light microscopic techniques enabled obtaining a more accurate description of the intestinal lesions than either technique alone.", "contents": "Scanning electron, light, and immunofluorescent microscopy of intestine of gnotobiotic calf infected with reovirus-like agent. Intestinal lesions caused by a calf diarrheal reovirus-like agent were studied by scanning electron microscopy, light microscopy, and immunofluorescent microscopy in 2 gnotobiotic calves inoculated per orum. The calves were euthanatized 6 hours after the onset of diarrhea. Villi in the cranial and middle parts of the small intestine appeared shortened. In these areas, the epithelium was composed of low columnar and cuboidal cells. Villi in the caudal part of the small intestine were short. By scanning electron microscopy, the villous epithelium in the caudal part of the small intestine of both calves and the ridge epithelium in the ansa spiralis coli of 1 calf were composed of various sized cells which gave the surfaces an irregular appearance. The amount of mucopolysaccharide in the colonic epithelial cells of both calves was greatly reduced. The combined use of scanning electron and light microscopic techniques enabled obtaining a more accurate description of the intestinal lesions than either technique alone."}
{"id": "PMID:195492", "title": "Specific suppression of the bursa-dependent immune system of chicks with infectious bursal disease virus.", "content": "Chicks which had been inoculated with infectious bursal disease virus (IBDV) at 1 day of age had a severe depression of bursa-dependent humoral immune functions by day 42. Antibody responses against rabbit red blood cells or to immunization with bovine serum albumin were significantly suppressed. In contrast, chicks inoculated with IBDV at 21 days of age produced near normal antibody responses as compared with the responses in noninfected control chicks. The IBDV had no significant effect on the thymus-dependent cellular responses as measured by skin graft rejection or delayed type hypersensitivity reactions to tuberculin.", "contents": "Specific suppression of the bursa-dependent immune system of chicks with infectious bursal disease virus. Chicks which had been inoculated with infectious bursal disease virus (IBDV) at 1 day of age had a severe depression of bursa-dependent humoral immune functions by day 42. Antibody responses against rabbit red blood cells or to immunization with bovine serum albumin were significantly suppressed. In contrast, chicks inoculated with IBDV at 21 days of age produced near normal antibody responses as compared with the responses in noninfected control chicks. The IBDV had no significant effect on the thymus-dependent cellular responses as measured by skin graft rejection or delayed type hypersensitivity reactions to tuberculin."}
{"id": "PMID:195493", "title": "Immunoglobulin G subclass [IgG and IgG(T)] interaction with the P26 group specific antigen of equine infectious anemia virus: immunodiffusion and complement-fixation reactions.", "content": "Isolated equine immunoglobulin (Ig)G(T) antibodies to equine infectious anemia virus P26 antigen did not precipitate with antigen when the ratio of antibody to antigen was high. However, at lower ratios of antibody to antigen precipitation occurred. In addition, complement-fixation by IgG and P26 antigen was inhibited by high concentrations of IgG(T). The unusual reaction pattern noted with IgG(T) antibodies was still detectable by the immunodiffusion test for equine infectious anemia virus. In situations of nonprecipitability by IgG(T), the adjacent positive control line was inhibited, and this was interpreted as a positive reaction.", "contents": "Immunoglobulin G subclass [IgG and IgG(T)] interaction with the P26 group specific antigen of equine infectious anemia virus: immunodiffusion and complement-fixation reactions. Isolated equine immunoglobulin (Ig)G(T) antibodies to equine infectious anemia virus P26 antigen did not precipitate with antigen when the ratio of antibody to antigen was high. However, at lower ratios of antibody to antigen precipitation occurred. In addition, complement-fixation by IgG and P26 antigen was inhibited by high concentrations of IgG(T). The unusual reaction pattern noted with IgG(T) antibodies was still detectable by the immunodiffusion test for equine infectious anemia virus. In situations of nonprecipitability by IgG(T), the adjacent positive control line was inhibited, and this was interpreted as a positive reaction."}
{"id": "PMID:195494", "title": "Equine herpesvirus 1 infection of horses: studies on the experimentally induced neurologic disease.", "content": "Experimental infection with equine herpesvirus 1 (rhinopneumonitis) resulted in neurologic disease in 8 of 15 inoculated horses. Nonpregnant animals did not develop clinical disease, and microscopic examination of tissues revealed no changes. In all mares between 3 and 9 months of gestation, a neurologic syndrome appeared 6 to 8 days after inoculation. Mares inoculated when 10 months pregnant did not develop neurologic disorders, but several aborted. The histopathologic change common to both sequelae was vasculitis, involving smaller arteries and veins. Although blood vessel changes were detected in endometrium of all pregnant mares, vascular changes were present in the central nervous  system only in mares having neurologic disease. Concomitant degeneration of nervous tissue occurred within the central nervous system and, in many sites, anatomic and temporal relationships of vasculitis and nervous tissue degeneration suggested a cause-effect relationship. This theory was strengthened by the lack of usual histopathologic indications of encephalomyelitis. In cerebrospinal fluid from affected mares, there was an increase in protein but not pleocytosis.", "contents": "Equine herpesvirus 1 infection of horses: studies on the experimentally induced neurologic disease. Experimental infection with equine herpesvirus 1 (rhinopneumonitis) resulted in neurologic disease in 8 of 15 inoculated horses. Nonpregnant animals did not develop clinical disease, and microscopic examination of tissues revealed no changes. In all mares between 3 and 9 months of gestation, a neurologic syndrome appeared 6 to 8 days after inoculation. Mares inoculated when 10 months pregnant did not develop neurologic disorders, but several aborted. The histopathologic change common to both sequelae was vasculitis, involving smaller arteries and veins. Although blood vessel changes were detected in endometrium of all pregnant mares, vascular changes were present in the central nervous  system only in mares having neurologic disease. Concomitant degeneration of nervous tissue occurred within the central nervous system and, in many sites, anatomic and temporal relationships of vasculitis and nervous tissue degeneration suggested a cause-effect relationship. This theory was strengthened by the lack of usual histopathologic indications of encephalomyelitis. In cerebrospinal fluid from affected mares, there was an increase in protein but not pleocytosis."}
{"id": "PMID:195495", "title": "Clinical, serologic, and cross-challenge response and virus isolation in cattle infected with three bovine dermatotropic herpesviruses.", "content": "The relationship of 3 dermatotropic bovine herpes-viruses (bovine mamillitis herpesvirus, dermatotropic bovine herpesvirus, and Allerton virus) was investigated; special emphasis was on the clinical response and the development of complement-fixation and precipitating antibodies in cattle. The immune respnse in steers was determined throughout the disease and after challenge exposure of the steers with 1 of the other 2 herpesviruses. Blood samples and sections of skin were collected intermittently from infected animals and examined for presence of virus.", "contents": "Clinical, serologic, and cross-challenge response and virus isolation in cattle infected with three bovine dermatotropic herpesviruses. The relationship of 3 dermatotropic bovine herpes-viruses (bovine mamillitis herpesvirus, dermatotropic bovine herpesvirus, and Allerton virus) was investigated; special emphasis was on the clinical response and the development of complement-fixation and precipitating antibodies in cattle. The immune respnse in steers was determined throughout the disease and after challenge exposure of the steers with 1 of the other 2 herpesviruses. Blood samples and sections of skin were collected intermittently from infected animals and examined for presence of virus."}
{"id": "PMID:195497", "title": "Immunoglobulin response to bluetongue virus soluble antigen in subcutaneous chambers.", "content": "Group-specific antibodies were produced by inoculation of bluetongue virus soluble antigen into polyethylene chambers implanted subcutaneously in 8 rabbits and 2 sheep. For comparison, 5 rabbits and 1 sheep were inoculated intramuscularly with the soluble antigen in Freund's complete adjuvant. Antibodies present in the serum and chamber fluids were detected by the agar gel precipitin or serum-neutralization tests, qualitatively examined by immunoelectrophoresis and immunofluorescence, and quantitated by electroimmunodiffusion.", "contents": "Immunoglobulin response to bluetongue virus soluble antigen in subcutaneous chambers. Group-specific antibodies were produced by inoculation of bluetongue virus soluble antigen into polyethylene chambers implanted subcutaneously in 8 rabbits and 2 sheep. For comparison, 5 rabbits and 1 sheep were inoculated intramuscularly with the soluble antigen in Freund's complete adjuvant. Antibodies present in the serum and chamber fluids were detected by the agar gel precipitin or serum-neutralization tests, qualitatively examined by immunoelectrophoresis and immunofluorescence, and quantitated by electroimmunodiffusion."}
{"id": "PMID:195498", "title": "Reproduction and treatment of necrotic enteritis in broilers.", "content": "A change in ration from one containing 50% fish meal to a standard chick starter containing 10(8) Clostridium perfringens/g of feed resulted in the production of necrotic enteritis in 2-week-old broiler chicks. Lincomycin added to the inoculated ration at a concentration of 20 g/907.2 kg significantly reduced mortality in the chicks. Inoculation of broth cultures of C perfringens directly into the duodenum, using a surgically inserted tetrafluoroethylene resin tube, indicated a relationship existed between the number of C perfringens inoculated and the gross lesions. The disease could be consistently produced by this technique.", "contents": "Reproduction and treatment of necrotic enteritis in broilers. A change in ration from one containing 50% fish meal to a standard chick starter containing 10(8) Clostridium perfringens/g of feed resulted in the production of necrotic enteritis in 2-week-old broiler chicks. Lincomycin added to the inoculated ration at a concentration of 20 g/907.2 kg significantly reduced mortality in the chicks. Inoculation of broth cultures of C perfringens directly into the duodenum, using a surgically inserted tetrafluoroethylene resin tube, indicated a relationship existed between the number of C perfringens inoculated and the gross lesions. The disease could be consistently produced by this technique."}
{"id": "PMID:195499", "title": "Effects on interferon of heavy metal excess and zinc deficiency.", "content": "Near toxic concentrations of cadmium sulfate, mercuric chloride, and nickel sulfate reduced interferon action in tissue cultures, but increased intake by the intact mouse of lead acetate and mercuric chloride did not reduce interferon action. Lead and nickel given orally inhibited the protective activity of Newcastle disease virus against encephalomyocarditis virus-induced mortality, whereas cadmium, mercury, cobalt sulfate, and sodium arsenite given orally and deficiency of zinc did not influence this action. Excess lead and cobalt and deficiency of zinc, but not excess cadmium, mercury, or nickel, inhibited the protective activity of poly I/poly C against encephalomyocarditis virus-induced mortality. These results illustrate the various actions of increased concentrations of certain metals or a deficiency of zinc on interferon action or on actions of interferon inducers.", "contents": "Effects on interferon of heavy metal excess and zinc deficiency. Near toxic concentrations of cadmium sulfate, mercuric chloride, and nickel sulfate reduced interferon action in tissue cultures, but increased intake by the intact mouse of lead acetate and mercuric chloride did not reduce interferon action. Lead and nickel given orally inhibited the protective activity of Newcastle disease virus against encephalomyocarditis virus-induced mortality, whereas cadmium, mercury, cobalt sulfate, and sodium arsenite given orally and deficiency of zinc did not influence this action. Excess lead and cobalt and deficiency of zinc, but not excess cadmium, mercury, or nickel, inhibited the protective activity of poly I/poly C against encephalomyocarditis virus-induced mortality. These results illustrate the various actions of increased concentrations of certain metals or a deficiency of zinc on interferon action or on actions of interferon inducers."}
{"id": "PMID:195500", "title": "Effects of heavy metals and of deficiency of zinc on mortality rates in mice infected with encephalomyocarditis virus.", "content": "Salts of cadmium, lead, mercury, and nickel given orally to mice increased encephalomyocarditis virus-induced mortality rates. Although lead was the least toxic of the 4 metals, it enhanced the mortality the most. Concentrations of mercuric chloride as low as 0.01 ppm intensified the mortality; a minimal concentration that resulted in no effect was not ascertained. Zinc deficiency caused pronounced retardation of growth in young mice, but it did not influence mortality due to encephalomyocarditis virus.", "contents": "Effects of heavy metals and of deficiency of zinc on mortality rates in mice infected with encephalomyocarditis virus. Salts of cadmium, lead, mercury, and nickel given orally to mice increased encephalomyocarditis virus-induced mortality rates. Although lead was the least toxic of the 4 metals, it enhanced the mortality the most. Concentrations of mercuric chloride as low as 0.01 ppm intensified the mortality; a minimal concentration that resulted in no effect was not ascertained. Zinc deficiency caused pronounced retardation of growth in young mice, but it did not influence mortality due to encephalomyocarditis virus."}
{"id": "PMID:195501", "title": "Evidence for the replication of bovine leukemia virus in the B lymphocytes.", "content": "Bovine peripheral blood lymphocytes from a cow with persistent lymphocytosis were separated on nylon wool columns into nylon-adherent and nonadherent populations. Nylon-adherent cells were highly enriched for surface immunoglobulin (SIg) bearing B lymphocytes (95.5%) and nonadherent cells for SIg negative non-B cells, presumably T lymphocytes (96.3%). The B lymphocytes were found to be the major producers for bovine leukemia virus. A total of 39% of the B-enriched cells, surviving after 72 hours in culture, produced bovine leukemia virus as compared with 0.5% of the non-B cells.", "contents": "Evidence for the replication of bovine leukemia virus in the B lymphocytes. Bovine peripheral blood lymphocytes from a cow with persistent lymphocytosis were separated on nylon wool columns into nylon-adherent and nonadherent populations. Nylon-adherent cells were highly enriched for surface immunoglobulin (SIg) bearing B lymphocytes (95.5%) and nonadherent cells for SIg negative non-B cells, presumably T lymphocytes (96.3%). The B lymphocytes were found to be the major producers for bovine leukemia virus. A total of 39% of the B-enriched cells, surviving after 72 hours in culture, produced bovine leukemia virus as compared with 0.5% of the non-B cells."}
{"id": "PMID:195503", "title": "Current management of carcinoma of the anus and perianus.", "content": "Malignant lesions of the anus and perianus account for 2.4% of malignant cancers of the colon, rectum, and anus. Based on our experience with 56 patients as well as a review of the recent literature, the following recommendations are made: Bowen's disease, Paget's extramammary disease, basal cell, and perianal epidermoid carcinomas arise in the perianus, rarely metastasize, and may be managed by wide local excision. Cloacogenic transitional cell (basaloid squamous carcinoma) and the more common epidermoid anal canal tumors require abdominoperineal resection with wide perineal excision. Therapeutic groin dissection is indicated if the inguinal nodes are or become the site of metastases, but prophylactic groin dissection is not indicated. The five-year survival for epidermoid carcinoma of anus treated by abdominoperineal resection ranges from 40 to 58%. Improvement in survival rate will require early recognition by the patient and early diagnosis and treatment by the physician. Delay in diagnosis occurs because cancer is not considered frequently enough as a possible cause for the patient's symptoms.", "contents": "Current management of carcinoma of the anus and perianus. Malignant lesions of the anus and perianus account for 2.4% of malignant cancers of the colon, rectum, and anus. Based on our experience with 56 patients as well as a review of the recent literature, the following recommendations are made: Bowen's disease, Paget's extramammary disease, basal cell, and perianal epidermoid carcinomas arise in the perianus, rarely metastasize, and may be managed by wide local excision. Cloacogenic transitional cell (basaloid squamous carcinoma) and the more common epidermoid anal canal tumors require abdominoperineal resection with wide perineal excision. Therapeutic groin dissection is indicated if the inguinal nodes are or become the site of metastases, but prophylactic groin dissection is not indicated. The five-year survival for epidermoid carcinoma of anus treated by abdominoperineal resection ranges from 40 to 58%. Improvement in survival rate will require early recognition by the patient and early diagnosis and treatment by the physician. Delay in diagnosis occurs because cancer is not considered frequently enough as a possible cause for the patient's symptoms."}
{"id": "PMID:195505", "title": "Transmission of non-A, non-B hepatitis.", "content": "In studies conducted in the early 1950s, sera from six asymptomatic blood donors, implicated in the transmission of viral hepatitis, were inoculated into 10 to 20 volunteers each. Five of these \"implicated\" donor sera transmitted clinically apparent hepatitis to the recipients. The stored serum samples from these studies have been reanalyzed using serologic markers for hepatitis B virus and hepatitis A virus infection. Two of the donor sera were hepatitis B surface antigen (HBsAg)-positive, and both transmitted hepatitis B virus infection to all susceptible recipients, half of whom showing clinical symptoms. The remaining three infectious donors were HBs-Ag-negative, yet were icterogenic to 10% to 47% of recipients. Testing of serum samples from these recipients with hepatitis showed no evidence of hepatitis B virus or hepatitis A virus infection. This study and other recent evidence suggest that there is a third type of human viral hepatitis--non-A, non-B hepatitis--which is due to a transmissible agent and may well be associated with a chronic carrier state.", "contents": "Transmission of non-A, non-B hepatitis. In studies conducted in the early 1950s, sera from six asymptomatic blood donors, implicated in the transmission of viral hepatitis, were inoculated into 10 to 20 volunteers each. Five of these \"implicated\" donor sera transmitted clinically apparent hepatitis to the recipients. The stored serum samples from these studies have been reanalyzed using serologic markers for hepatitis B virus and hepatitis A virus infection. Two of the donor sera were hepatitis B surface antigen (HBsAg)-positive, and both transmitted hepatitis B virus infection to all susceptible recipients, half of whom showing clinical symptoms. The remaining three infectious donors were HBs-Ag-negative, yet were icterogenic to 10% to 47% of recipients. Testing of serum samples from these recipients with hepatitis showed no evidence of hepatitis B virus or hepatitis A virus infection. This study and other recent evidence suggest that there is a third type of human viral hepatitis--non-A, non-B hepatitis--which is due to a transmissible agent and may well be associated with a chronic carrier state."}
{"id": "PMID:195506", "title": "Parenterally transmitted non-A, non-B hepatitis: an epidemic reassessed.", "content": "In 1972 a nonsocomial outbreak of parenterally transmitted hepatitis affected both marrow transplant patients and normal platelet donors in an oncology unit. Because of the characteristics of the clinical illness, the incubation period of 27 days, and the effect of immune serum globulin on the clinical illness, the outbreak was attributed to hepatitis A; there was no serologic evidence of either hepatitis B virus or cytomegalovirus infection. Stored serums from this outbreak were re-examined by more recently developed serologic techniques for evidence of hepatitis A (HA) virus infection. Ten patients and donors had undetectable anti-HA titers before illness and none seroconverted; five persons had pre-existent anti-HA titers and showed no further rise in convalescent serums. The serum of one patient was inevaluable. With the availability of serologic techniques for the diagnosis of both hepatitis A and hepatitis B virus infections, it is clear that most cases of post-transfusion hepatitis are not due to either of these agents, and short-incubation-period hepatitis can not be assumed to be hepatitis A without further investigation.", "contents": "Parenterally transmitted non-A, non-B hepatitis: an epidemic reassessed. In 1972 a nonsocomial outbreak of parenterally transmitted hepatitis affected both marrow transplant patients and normal platelet donors in an oncology unit. Because of the characteristics of the clinical illness, the incubation period of 27 days, and the effect of immune serum globulin on the clinical illness, the outbreak was attributed to hepatitis A; there was no serologic evidence of either hepatitis B virus or cytomegalovirus infection. Stored serums from this outbreak were re-examined by more recently developed serologic techniques for evidence of hepatitis A (HA) virus infection. Ten patients and donors had undetectable anti-HA titers before illness and none seroconverted; five persons had pre-existent anti-HA titers and showed no further rise in convalescent serums. The serum of one patient was inevaluable. With the availability of serologic techniques for the diagnosis of both hepatitis A and hepatitis B virus infections, it is clear that most cases of post-transfusion hepatitis are not due to either of these agents, and short-incubation-period hepatitis can not be assumed to be hepatitis A without further investigation."}
{"id": "PMID:195508", "title": "Pathophysiology of myocardial infarction.", "content": "Primary prevention of death from ischemic heart disease requires further understanding of the pathogenesis of this disorder. Cellular defects of cholesterol metabolism may be more significant markers that serum lipid levels for the identification and treatment of atherosclerotic risk. Coronary spasm has been shown to be an important cause of ischemia in the presence and absence of atherosclerotic lesions. Careful manipulation of physiologic variables with vasodilator agents during cardiopulmonary bypass can substantially alter the myocardial oxygen supply-demand relation, thereby minimizing ischemic injury. The cellular basis for loss of mechanical function during ischemia and the factors that determine irreversible injury are yet unknown.", "contents": "Pathophysiology of myocardial infarction. Primary prevention of death from ischemic heart disease requires further understanding of the pathogenesis of this disorder. Cellular defects of cholesterol metabolism may be more significant markers that serum lipid levels for the identification and treatment of atherosclerotic risk. Coronary spasm has been shown to be an important cause of ischemia in the presence and absence of atherosclerotic lesions. Careful manipulation of physiologic variables with vasodilator agents during cardiopulmonary bypass can substantially alter the myocardial oxygen supply-demand relation, thereby minimizing ischemic injury. The cellular basis for loss of mechanical function during ischemia and the factors that determine irreversible injury are yet unknown."}
{"id": "PMID:195510", "title": "[Epitheliomas of the retro-molar trigone and of the inside surface of the cheeks (author's transl)].", "content": "The authors have made a study of 53 cases of tumours of the retro-molar trigone and of the internal surface of the cheeks which were treated between 1959 and 1972; these were malphigian epitheliomas except for one case of cylindroma. The research is concerned with the choice of methods and the therapeutic indications. Retro-molar trigones call for combined telecobaltherapy-electrontherapy;--curie-therapy is too difficult in this area. Electrontherapy may be used on alternate days with telecobaltherapy or as a booster dose after external irradiation by cobaltherapy. In cases of epitheliomas of the cheek, curietherapy or electrontherapy may be used after external irradiation or in isolation for tumours which are small in size. Therapeutic results are satisfactory in lesions at the outset (7/8 and 7/9), for T1-T2. For advanced lesions T3 of the trigone (6/16) and especially for those of the internal surface of the cheeks (2/9), the success rate is considerably lower; in lesions of the T4 type, a palliative effect was obtained but without any definite improvement.", "contents": "[Epitheliomas of the retro-molar trigone and of the inside surface of the cheeks (author's transl)]. The authors have made a study of 53 cases of tumours of the retro-molar trigone and of the internal surface of the cheeks which were treated between 1959 and 1972; these were malphigian epitheliomas except for one case of cylindroma. The research is concerned with the choice of methods and the therapeutic indications. Retro-molar trigones call for combined telecobaltherapy-electrontherapy;--curie-therapy is too difficult in this area. Electrontherapy may be used on alternate days with telecobaltherapy or as a booster dose after external irradiation by cobaltherapy. In cases of epitheliomas of the cheek, curietherapy or electrontherapy may be used after external irradiation or in isolation for tumours which are small in size. Therapeutic results are satisfactory in lesions at the outset (7/8 and 7/9), for T1-T2. For advanced lesions T3 of the trigone (6/16) and especially for those of the internal surface of the cheeks (2/9), the success rate is considerably lower; in lesions of the T4 type, a palliative effect was obtained but without any definite improvement."}
{"id": "PMID:195513", "title": "[Molecular mechanism of the action of lucanthone on tumor and normal cells].", "content": "The standard analytical and preparative electrophoresis in polyacrylamide gel did not reveal qualitative differences in the fraction composition of c-RNA of the ascitic tumour cells (Zaidel hepatoma, Ehrlich carcinoma, NK/ly lymphoma) and normal liver cells. In vitro the tumour and normal cells efficiently incorporated the labeled uridine into the all main classes of c-RNA (4S, 18S, 28S, fractions above 28S), the process being more intensive in the tumour cells. The presence of tumours in the animal organism had a significant effect on RNA biosynthesis in the liver, the effect being dependent on the tumor nature. Lucantone (miracyl D) had practically no effect in vitro on the quantitative content of the summation c-RNA and its fractions in all cells studied. However, it markedly inhibited the metabolism of the main fractions of c-RNA in the cells of Zaidel hepatoma and Ehrlich carcinoma. The effect of lucatone in the cells of NK/ly lymphoma was contrary.", "contents": "[Molecular mechanism of the action of lucanthone on tumor and normal cells]. The standard analytical and preparative electrophoresis in polyacrylamide gel did not reveal qualitative differences in the fraction composition of c-RNA of the ascitic tumour cells (Zaidel hepatoma, Ehrlich carcinoma, NK/ly lymphoma) and normal liver cells. In vitro the tumour and normal cells efficiently incorporated the labeled uridine into the all main classes of c-RNA (4S, 18S, 28S, fractions above 28S), the process being more intensive in the tumour cells. The presence of tumours in the animal organism had a significant effect on RNA biosynthesis in the liver, the effect being dependent on the tumor nature. Lucantone (miracyl D) had practically no effect in vitro on the quantitative content of the summation c-RNA and its fractions in all cells studied. However, it markedly inhibited the metabolism of the main fractions of c-RNA in the cells of Zaidel hepatoma and Ehrlich carcinoma. The effect of lucatone in the cells of NK/ly lymphoma was contrary."}
{"id": "PMID:195514", "title": "Phosphonoacetic acid-resistant mutants of herpes simplex virus: effect of phosphonoacetic acid on virus replication and in vitro deoxyribonucleic acid synthesis in isolated nuclei.", "content": "Phosphonoacetic acid (PAA) inhibits the replication of herpes simplex virus in BSC-1 cells and the in vitro synthesis of deoxyribonucleic acid (DNA) in isolated nuclei. Phosphonopropionic acid at a concentration of 100 mug/ml had no effect on herpes simplex virus replication. PAA-resistant mutants were obtained at a rate of 1 in 10(4) plaque-forming units after 5-bromodeoxyuridine mutagenization of the virus. These mutants replicate in BSC-1 cells in the presence of 100 mug of PAA per ml and induce a PAA-resistant DNA polymerase that synthesizes DNA in vitro in the presence of PAA.", "contents": "Phosphonoacetic acid-resistant mutants of herpes simplex virus: effect of phosphonoacetic acid on virus replication and in vitro deoxyribonucleic acid synthesis in isolated nuclei. Phosphonoacetic acid (PAA) inhibits the replication of herpes simplex virus in BSC-1 cells and the in vitro synthesis of deoxyribonucleic acid (DNA) in isolated nuclei. Phosphonopropionic acid at a concentration of 100 mug/ml had no effect on herpes simplex virus replication. PAA-resistant mutants were obtained at a rate of 1 in 10(4) plaque-forming units after 5-bromodeoxyuridine mutagenization of the virus. These mutants replicate in BSC-1 cells in the presence of 100 mug of PAA per ml and induce a PAA-resistant DNA polymerase that synthesizes DNA in vitro in the presence of PAA."}
{"id": "PMID:195515", "title": "Inhibition of herpes simplex virus strains isolated from herpetic keratitis by polyinosinic acid-polycytidylic acid.", "content": "Fifty strains of herpes simplex virus, isolated from patients with herpetic keratitis, were examined in vitro for susceptibility to polyinosinic acid-polycytidylic acid [poly(I:C)] in the presence of a constant concentration of diethylaminoethyl-dextran. The minimal inhibitory concentration of poly(I:C) for 44 of these strains ranged from 0.0001 to 0.1 mug/ml; for the remaining six strains, the minimal inhibitory concentration stood at 1 to 2 mug/ml. Fifteen isolates from primary infections were more susceptible to poly(I:C) than 35 isolates from recurrent infections. Isolates acquired at different points of a given clinical episode showed similar susceptibilities to poly(I:C). In two patients, isolates from consecutive recurrences of infection exhibited reduced susceptibilities. The implications of the above observations for the therapeutic use of poly(I:C) are discussed.", "contents": "Inhibition of herpes simplex virus strains isolated from herpetic keratitis by polyinosinic acid-polycytidylic acid. Fifty strains of herpes simplex virus, isolated from patients with herpetic keratitis, were examined in vitro for susceptibility to polyinosinic acid-polycytidylic acid [poly(I:C)] in the presence of a constant concentration of diethylaminoethyl-dextran. The minimal inhibitory concentration of poly(I:C) for 44 of these strains ranged from 0.0001 to 0.1 mug/ml; for the remaining six strains, the minimal inhibitory concentration stood at 1 to 2 mug/ml. Fifteen isolates from primary infections were more susceptible to poly(I:C) than 35 isolates from recurrent infections. Isolates acquired at different points of a given clinical episode showed similar susceptibilities to poly(I:C). In two patients, isolates from consecutive recurrences of infection exhibited reduced susceptibilities. The implications of the above observations for the therapeutic use of poly(I:C) are discussed."}
{"id": "PMID:195516", "title": "Induction of bacteriocins from Clostridium perfringens by treatment with mitomycin C.", "content": "Six of ten bacteriocinogenic strains of Clostridium perfringens were inducible by treating the cultures with mitomycin C. Induction did not occur in the continued presence of mitomycin C but only when excess mitomycin C was removed. Cell death was associated with induction of bacteriocin.", "contents": "Induction of bacteriocins from Clostridium perfringens by treatment with mitomycin C. Six of ten bacteriocinogenic strains of Clostridium perfringens were inducible by treating the cultures with mitomycin C. Induction did not occur in the continued presence of mitomycin C but only when excess mitomycin C was removed. Cell death was associated with induction of bacteriocin."}
{"id": "PMID:195517", "title": "Cyclic adenylic acid-dependent and -independent production of chloramphenicol acetyltransferase in Escherichia coli carrying R plasmids.", "content": "A plasmid-specified, inducible, but cyclic adenylic acid (cAMP)-independent resistance to chloramphenicol (CM) is reported. The resistance level to CM was increased two- to fourfold by treatment with a small amount of CM for a short period in Escherichia coli strains carrying the R plasmid pJY1, which was obtained from a clinical isolate of Vibrio cholerae. Though cAMP was required for production of CM acetyltransferase (CATase) in cAMP-deficient mutants of E. coli carrying the R100 plasmid, the same species harboring pJY1 did not require cAMP for production of the enzyme. The possibility of a mechanism other than CATase activity for the CM resistance conferred by R plasmids is discussed.", "contents": "Cyclic adenylic acid-dependent and -independent production of chloramphenicol acetyltransferase in Escherichia coli carrying R plasmids. A plasmid-specified, inducible, but cyclic adenylic acid (cAMP)-independent resistance to chloramphenicol (CM) is reported. The resistance level to CM was increased two- to fourfold by treatment with a small amount of CM for a short period in Escherichia coli strains carrying the R plasmid pJY1, which was obtained from a clinical isolate of Vibrio cholerae. Though cAMP was required for production of CM acetyltransferase (CATase) in cAMP-deficient mutants of E. coli carrying the R100 plasmid, the same species harboring pJY1 did not require cAMP for production of the enzyme. The possibility of a mechanism other than CATase activity for the CM resistance conferred by R plasmids is discussed."}
{"id": "PMID:195518", "title": "Inactivation of poliovirus in wastewater sludge with radiation and thermoradiation.", "content": "Sludge is highly protective of poliovirus against both heat and ionizing radiation. This protection could be largely overcome when these two treatments were given simultaneously.", "contents": "Inactivation of poliovirus in wastewater sludge with radiation and thermoradiation. Sludge is highly protective of poliovirus against both heat and ionizing radiation. This protection could be largely overcome when these two treatments were given simultaneously."}
{"id": "PMID:195538", "title": "Hutchinson's Archives of Surgery revisited.", "content": "I present a bried review of Hutchinson's Archives of Surgery. I have listed most of his well-known and not-so-well-known early clinical descriptions. To this list can be added descriptions of Peutz-Jegher syndrome, lipomelanic reticulosis, telangiectatic lupus erythematosus, temporal arteritis, and recurrent herpes simplex on the thigh and buttocks. The characteristics of Hutchinson's writing are the use of catchy, descriptive terms, his use of patients' names for diseases, his belief in the effectiveness of illustrations, superb clinical observation but faulty conclusions, and a lack of humor. Seventy-two years after his death, there is still much that can be learned about clinical disease from Hutchinson.", "contents": "Hutchinson's Archives of Surgery revisited. I present a bried review of Hutchinson's Archives of Surgery. I have listed most of his well-known and not-so-well-known early clinical descriptions. To this list can be added descriptions of Peutz-Jegher syndrome, lipomelanic reticulosis, telangiectatic lupus erythematosus, temporal arteritis, and recurrent herpes simplex on the thigh and buttocks. The characteristics of Hutchinson's writing are the use of catchy, descriptive terms, his use of patients' names for diseases, his belief in the effectiveness of illustrations, superb clinical observation but faulty conclusions, and a lack of humor. Seventy-two years after his death, there is still much that can be learned about clinical disease from Hutchinson."}
{"id": "PMID:195540", "title": "Pulmonary involvement with cytomegalovirus infections in children.", "content": "Among 40 hospitalized infants and children with cytomegalovirus infection, 14 (35%) had interstitial pneumonitis, 4 (10%) had wheezing or tachypnoea but without x-ray evidence of classical interstitial pneumonia, the remaining 22 (55%) were free of pulmonary involvement. Most patients had tachypnoea and nonproductive cough of varying durations: those with underlying pulmonary pathology tended to have persistent and prolonged respiratory symptoms. Mortality and severity of the lung disease were related to the underlying immunodeficiency or concomitant pulmonary process.", "contents": "Pulmonary involvement with cytomegalovirus infections in children. Among 40 hospitalized infants and children with cytomegalovirus infection, 14 (35%) had interstitial pneumonitis, 4 (10%) had wheezing or tachypnoea but without x-ray evidence of classical interstitial pneumonia, the remaining 22 (55%) were free of pulmonary involvement. Most patients had tachypnoea and nonproductive cough of varying durations: those with underlying pulmonary pathology tended to have persistent and prolonged respiratory symptoms. Mortality and severity of the lung disease were related to the underlying immunodeficiency or concomitant pulmonary process."}
{"id": "PMID:195541", "title": "Intestinal damage in rotavirus and adenovirus gastroenteritis assessed by d-xylose malabsorption.", "content": "The absorption of D-xylose infused into the duodenum was assessed in infants with acute gastroenteritis. 1-hour blood-xylose levels were low in 6 patients found to harbour rotavirus in the small intestinal aspirate. Normal levels (greater than 1-26 mmol/l) were obtained in the absence of virus particles in the small intestine in a further 6 patients: in 3 of these adenovirus or rotavirus was recovered from the stools. Three patients with adenovirus in the small intestinal juice and ill with acute gastroenteritis also had low xylose levels. This finding supports earlier epidemiological studies that adenovirus may be a causative agent of acute infantile gastroenteritis. The association between virus in the small intestine and xylose malabsorption may indicate mucosal damage. Formal proff of this is awaited.", "contents": "Intestinal damage in rotavirus and adenovirus gastroenteritis assessed by d-xylose malabsorption. The absorption of D-xylose infused into the duodenum was assessed in infants with acute gastroenteritis. 1-hour blood-xylose levels were low in 6 patients found to harbour rotavirus in the small intestinal aspirate. Normal levels (greater than 1-26 mmol/l) were obtained in the absence of virus particles in the small intestine in a further 6 patients: in 3 of these adenovirus or rotavirus was recovered from the stools. Three patients with adenovirus in the small intestinal juice and ill with acute gastroenteritis also had low xylose levels. This finding supports earlier epidemiological studies that adenovirus may be a causative agent of acute infantile gastroenteritis. The association between virus in the small intestine and xylose malabsorption may indicate mucosal damage. Formal proff of this is awaited."}
{"id": "PMID:195542", "title": "Variations in adrenocortical responsiveness during severe bacterial infections. Unrecognized adrenocortical insufficiency in severe bacterial infections.", "content": "Plasma cortisol levels and their response to .25 mg synthetic A.C.T.H. (Cortrosyn) were studied in 26 septic patients. Four (15.4%) of these patients appeared to have greatly increased adrenocortical activity with plasma cortisol levels averaging 65.4 +/- 14.8 microgram/dl (normal = 8-18 microgram/dl. All four of these patients were agonal and died within five days. Seventeen (65.4%) of these 26 patients appeared to have an appropriate adrenocortical response to severe infection in that their plasma cortisol levels increased (averaging 19.2 +/- 6.0 microngram/dl) following synthetic A.C.T.H. The remaining five patients, who constituted 19.2% of the 26 patients studied, appeared to have some impairment of adrenocortical function. In spite of severe bacterial infections and no history to support Addison's disease, their plasma cortisol levels (averaging 13.8 +/- 3.3 microgram/dl) were not increased above normal and their response to Cortrosyn was much less than would be expected; the increase in plasma cortisol levels in these patients following the synthetic A.C.T.H. averaged 1.1 +/- 3.6 microgram/dl. It is reemphasized that patients with severe sepsis who are not responding adequately to standard therapy should be suspected of having adrenocortical insufficiency and treated accordingly.", "contents": "Variations in adrenocortical responsiveness during severe bacterial infections. Unrecognized adrenocortical insufficiency in severe bacterial infections. Plasma cortisol levels and their response to .25 mg synthetic A.C.T.H. (Cortrosyn) were studied in 26 septic patients. Four (15.4%) of these patients appeared to have greatly increased adrenocortical activity with plasma cortisol levels averaging 65.4 +/- 14.8 microgram/dl (normal = 8-18 microgram/dl. All four of these patients were agonal and died within five days. Seventeen (65.4%) of these 26 patients appeared to have an appropriate adrenocortical response to severe infection in that their plasma cortisol levels increased (averaging 19.2 +/- 6.0 microngram/dl) following synthetic A.C.T.H. The remaining five patients, who constituted 19.2% of the 26 patients studied, appeared to have some impairment of adrenocortical function. In spite of severe bacterial infections and no history to support Addison's disease, their plasma cortisol levels (averaging 13.8 +/- 3.3 microgram/dl) were not increased above normal and their response to Cortrosyn was much less than would be expected; the increase in plasma cortisol levels in these patients following the synthetic A.C.T.H. averaged 1.1 +/- 3.6 microgram/dl. It is reemphasized that patients with severe sepsis who are not responding adequately to standard therapy should be suspected of having adrenocortical insufficiency and treated accordingly."}
{"id": "PMID:195543", "title": "Regional pancreatectomy: en bloc pancreatic, portal vein and lymph node resection.", "content": "Eighteen patients are reported who have had a regional pancreatectomy. The pancreatic segment of portal vein was excised with en bloc total pancreatectomy and regional lymph node dissection in all 18. Venous repair was by end-to-end anastomosis without a graft. Five of the 18 also had various arterial resections and reconstructions. Sixteen of the 18 had been explored and deemed nonresectable elsewhere. This operation has doubled the resectability rate in this institution. The 30-day operative mortality rate was 16.6%. Acurarial survival is 62% at one year compared with 36% one year survival rate for patients undergoing pancreaticoduodenectomy for less advanced cancer in previous years. A more valid comparison would be between those who had a palliative procedure since most patients in the present series were initially considered unresectable. One year survival for these patients was 22%. The quality of life was good for most patients.", "contents": "Regional pancreatectomy: en bloc pancreatic, portal vein and lymph node resection. Eighteen patients are reported who have had a regional pancreatectomy. The pancreatic segment of portal vein was excised with en bloc total pancreatectomy and regional lymph node dissection in all 18. Venous repair was by end-to-end anastomosis without a graft. Five of the 18 also had various arterial resections and reconstructions. Sixteen of the 18 had been explored and deemed nonresectable elsewhere. This operation has doubled the resectability rate in this institution. The 30-day operative mortality rate was 16.6%. Acurarial survival is 62% at one year compared with 36% one year survival rate for patients undergoing pancreaticoduodenectomy for less advanced cancer in previous years. A more valid comparison would be between those who had a palliative procedure since most patients in the present series were initially considered unresectable. One year survival for these patients was 22%. The quality of life was good for most patients."}
{"id": "PMID:195544", "title": "The beta-adrenoceptors responsible for a direct relaxation of the uncontracted nictitating membrane of the anaesthetized cat.", "content": "Direct relaxation of the nictitating membrane of the anaesthetized cat was produced by close intra-arterial injections of single doses of isoprenaline and other beta-adrenoceptor agonists. This response was relatively resistant to blockade by doses of propranolol that almost abolished the corresponding positive chronotropic and vasodepressor responses. Construction of dose-response curves, however, revealed antagonism of all three parameters by propranolol and different sensitivities of the parameters to isoprenaline. The absence of blockade by practolol, although negative evidence, permitted the nictitating membrane response to be classified as a beta2-adrenoceptor effect, which was supported by the full agonist activity of salbutamol. The blockade of the nictitating membrane response by propranolol was however weaker than of the beta2-adrenoceptor mediated vasodepressor response. Contractile responses were observed with higher doses of isoprenaline and after intravenous injection. These were probably indirect effects induced by local changes in blood pressure at the nictitating membrane due to the concommitant vasodepressor response.", "contents": "The beta-adrenoceptors responsible for a direct relaxation of the uncontracted nictitating membrane of the anaesthetized cat. Direct relaxation of the nictitating membrane of the anaesthetized cat was produced by close intra-arterial injections of single doses of isoprenaline and other beta-adrenoceptor agonists. This response was relatively resistant to blockade by doses of propranolol that almost abolished the corresponding positive chronotropic and vasodepressor responses. Construction of dose-response curves, however, revealed antagonism of all three parameters by propranolol and different sensitivities of the parameters to isoprenaline. The absence of blockade by practolol, although negative evidence, permitted the nictitating membrane response to be classified as a beta2-adrenoceptor effect, which was supported by the full agonist activity of salbutamol. The blockade of the nictitating membrane response by propranolol was however weaker than of the beta2-adrenoceptor mediated vasodepressor response. Contractile responses were observed with higher doses of isoprenaline and after intravenous injection. These were probably indirect effects induced by local changes in blood pressure at the nictitating membrane due to the concommitant vasodepressor response."}
{"id": "PMID:195545", "title": "Influence of apomorphine on sympathetic neural transmission in the nictitating membrane of the cat.", "content": "Apomorphine inhibited the nictitating membrane contractions elicited by pre- or postganglionic stimulation of the cervical sympathetic nerve but did not influence even in higher doses the effect of noradrenaline and adrenaline on this organ. The inhibition evoked by apomorphine could be antagonized by haloperidol but was not influenced by phentolamine and propranolol. Dopamine and noradrenaline inhibited the nictitating membrane contractions elicited by nerve stimulation, but clonidine was ineffective in our experiments. Haloperidol antagonized the inhibition evoked by dopamine but did not influence the similar effect of noradrenaline.", "contents": "Influence of apomorphine on sympathetic neural transmission in the nictitating membrane of the cat. Apomorphine inhibited the nictitating membrane contractions elicited by pre- or postganglionic stimulation of the cervical sympathetic nerve but did not influence even in higher doses the effect of noradrenaline and adrenaline on this organ. The inhibition evoked by apomorphine could be antagonized by haloperidol but was not influenced by phentolamine and propranolol. Dopamine and noradrenaline inhibited the nictitating membrane contractions elicited by nerve stimulation, but clonidine was ineffective in our experiments. Haloperidol antagonized the inhibition evoked by dopamine but did not influence the similar effect of noradrenaline."}
{"id": "PMID:195546", "title": "Pharmacology of the hemodynamic and myocardial response to occlusion of the mesenteric artery in the cat.", "content": "Occlusion of the superior mesenteric artery in the cat produces increases in heart rate, systemic pressure, cardiac output and muscle blood flow. Total peripheral resistance is reduced and regional resistance in skin increased. Blockade of the right and left cardiac nerves with xylocaine lowered basal heart rate and reduced cardiac output. The increase in heart rate produced by occlusion of the artery (MAO) was prevented by blockade of the stellate ganglia and cardiac nerves. Propranolol lowered basal heart rate and cardiac output and subsequently blocked the increase in both parameters during MAO. The increase in muscle blood flow was also blocked resulting in an increase in total resistance. We conclude that, in the cat, MAO reflexly increases myocardial tone and enhances venous return from muscle, the latter by a reflex beta adrenergic vasodilation. Both factors provide for the increase in cardiac output. A reflex beta adrenergic vasodilation in muscle, evoked by vasoconstriction in the mesenteric bed, may contribute to survival in the hemorrhaged animals, since capillary exchange in muscle may be increased by this reflex and fluid shifted from the extra--to the intravascular compartment.", "contents": "Pharmacology of the hemodynamic and myocardial response to occlusion of the mesenteric artery in the cat. Occlusion of the superior mesenteric artery in the cat produces increases in heart rate, systemic pressure, cardiac output and muscle blood flow. Total peripheral resistance is reduced and regional resistance in skin increased. Blockade of the right and left cardiac nerves with xylocaine lowered basal heart rate and reduced cardiac output. The increase in heart rate produced by occlusion of the artery (MAO) was prevented by blockade of the stellate ganglia and cardiac nerves. Propranolol lowered basal heart rate and cardiac output and subsequently blocked the increase in both parameters during MAO. The increase in muscle blood flow was also blocked resulting in an increase in total resistance. We conclude that, in the cat, MAO reflexly increases myocardial tone and enhances venous return from muscle, the latter by a reflex beta adrenergic vasodilation. Both factors provide for the increase in cardiac output. A reflex beta adrenergic vasodilation in muscle, evoked by vasoconstriction in the mesenteric bed, may contribute to survival in the hemorrhaged animals, since capillary exchange in muscle may be increased by this reflex and fluid shifted from the extra--to the intravascular compartment."}
{"id": "PMID:195547", "title": "Primary and secondary cytomegalovirus infection.", "content": "Forty-seven patients who underwent renal transplants were followed clinically and were examined for serologic or virologic evidence of cytomegalovirus (CMV) infection. There were 18 cases of primary infection and ten cases of secondary infection. These findings were based on whether the patient was seronegative or seropositive prior to transplantation. Thirteen patients with primary infection and only one patient with secondary infection had two or more of the following manifestations that are temporally associated with laboratory evidence of infection: fever, leukopenia, atypical lymphocytes, lymphocytosis, hepatosplenomegaly, myalgia, arthralgia, and pneumonitis. Five patients with primary infections, one of whom died with disseminated disease, were recognized by attending physicians as having CMV disease. Since primary infection is though to be largely due to virus transmitted by the kidney of a seropositive donor, it may be possible to prevent symptomatic primary infection by using only seronegative donors for seronegative recipients.", "contents": "Primary and secondary cytomegalovirus infection. Forty-seven patients who underwent renal transplants were followed clinically and were examined for serologic or virologic evidence of cytomegalovirus (CMV) infection. There were 18 cases of primary infection and ten cases of secondary infection. These findings were based on whether the patient was seronegative or seropositive prior to transplantation. Thirteen patients with primary infection and only one patient with secondary infection had two or more of the following manifestations that are temporally associated with laboratory evidence of infection: fever, leukopenia, atypical lymphocytes, lymphocytosis, hepatosplenomegaly, myalgia, arthralgia, and pneumonitis. Five patients with primary infections, one of whom died with disseminated disease, were recognized by attending physicians as having CMV disease. Since primary infection is though to be largely due to virus transmitted by the kidney of a seropositive donor, it may be possible to prevent symptomatic primary infection by using only seronegative donors for seronegative recipients."}
{"id": "PMID:195549", "title": "Psychoses precipitated by psychotomimetic drugs. A follow-up study.", "content": "Fifteen patients who developed prolonged psychotic reactions following psychotomimetic drug use (probably primarily LSD) were followed up 1.9 to 5.8 years later. Two patients had committed suicide. Approximately half of the patients had a relatively good outcome and half did poorly. Aspects of the initial clinical picture that correlated with outcome measures are discussed. The possibility is considered that vulnerability to a prolonged psychotic reaction following psychotomimetic drug use may be related to a genetic vulnerability to illnesses in the manic-depressive/schizo-affective spectrum. In some instances this vulnerability may implicate central serotonergic neuronal systems.", "contents": "Psychoses precipitated by psychotomimetic drugs. A follow-up study. Fifteen patients who developed prolonged psychotic reactions following psychotomimetic drug use (probably primarily LSD) were followed up 1.9 to 5.8 years later. Two patients had committed suicide. Approximately half of the patients had a relatively good outcome and half did poorly. Aspects of the initial clinical picture that correlated with outcome measures are discussed. The possibility is considered that vulnerability to a prolonged psychotic reaction following psychotomimetic drug use may be related to a genetic vulnerability to illnesses in the manic-depressive/schizo-affective spectrum. In some instances this vulnerability may implicate central serotonergic neuronal systems."}
{"id": "PMID:195550", "title": "Cytochemical studies of respiratory enzymes in carcinoma of the cervix uteri after irradiation by radium and cobalt 60.", "content": "Enzymological studies of succinic dehydrogenase and cytochrome oxidase were made on human squamous cell carcinoma of the cervix uteri before, during and after radiation therapy by radium and 60CO. The enzymatic activities of the two enzymes were higher in cells of stage III than in the corresponding cells of stage II. In addition, after treatment, no enzymatic activity could be detected. These changes may be explained on the basis of mitochondrial damage as a result of radiation effect.", "contents": "Cytochemical studies of respiratory enzymes in carcinoma of the cervix uteri after irradiation by radium and cobalt 60. Enzymological studies of succinic dehydrogenase and cytochrome oxidase were made on human squamous cell carcinoma of the cervix uteri before, during and after radiation therapy by radium and 60CO. The enzymatic activities of the two enzymes were higher in cells of stage III than in the corresponding cells of stage II. In addition, after treatment, no enzymatic activity could be detected. These changes may be explained on the basis of mitochondrial damage as a result of radiation effect."}
{"id": "PMID:195551", "title": "Elimination of Proteus mirabilis 51Cr endotoxin from the liver in rats.", "content": "Using isotope methods, elimination of the endotoxin of Proteus mirabilis labeled with chromium (CrEPm) from the liver of rats was studied. The following studies were carried out: intravital exploration of the liver with a scintillation probe, measurements of radioactivity of organs and excreted urine and stools, scrintigraphy of the liver, binding of CrEPm by subcellular fractions of hepatocytes, and the influence of selected drugs (polymyxin and hydrocortisone) on elimination of CrEPm from the liver and organelles of hepatocytes.", "contents": "Elimination of Proteus mirabilis 51Cr endotoxin from the liver in rats. Using isotope methods, elimination of the endotoxin of Proteus mirabilis labeled with chromium (CrEPm) from the liver of rats was studied. The following studies were carried out: intravital exploration of the liver with a scintillation probe, measurements of radioactivity of organs and excreted urine and stools, scrintigraphy of the liver, binding of CrEPm by subcellular fractions of hepatocytes, and the influence of selected drugs (polymyxin and hydrocortisone) on elimination of CrEPm from the liver and organelles of hepatocytes."}
{"id": "PMID:195552", "title": "Mallory bodies compared with microfilament hyperplasia.", "content": "The binding characteristics of Mallory bodies (MBs) induced in livers of mice fed a long-term diet of griseofulvin were compared with the hyperplastic microfilaments induced by chronic phalloidin injections and with the MBs derived from livers of alcoholic patients at autopsy. Using the indirect immunofluorescence technique, smooth muscle antibody was shown to bind the hyperplastic microfilaments but not the human or mouse MBs. Peroxidase-antiperoxidase was shown to bind the human and mouse MBs but not the hyperplastic microfilaments. The evidence supports the idea that MBs are not composed of microfilaments (actin). The affinity of mouse and human MBs for peroxidase-antiperoxidase suggests that the MBs from these two species are chemically similar.", "contents": "Mallory bodies compared with microfilament hyperplasia. The binding characteristics of Mallory bodies (MBs) induced in livers of mice fed a long-term diet of griseofulvin were compared with the hyperplastic microfilaments induced by chronic phalloidin injections and with the MBs derived from livers of alcoholic patients at autopsy. Using the indirect immunofluorescence technique, smooth muscle antibody was shown to bind the hyperplastic microfilaments but not the human or mouse MBs. Peroxidase-antiperoxidase was shown to bind the human and mouse MBs but not the hyperplastic microfilaments. The evidence supports the idea that MBs are not composed of microfilaments (actin). The affinity of mouse and human MBs for peroxidase-antiperoxidase suggests that the MBs from these two species are chemically similar."}
{"id": "PMID:195553", "title": "Superficial cystic gastritis with alopecia. A forme fruste of the Cronkhite-Canada syndrome.", "content": "The Cronkhite-Canada syndrome is a rare and often fatal condition. A case of superficial cystic gastritis was suspected on peroral gastric biopsy and was later confirmed at autopsy. The selective involvement of the stomach together with the presence of alopecia leads us to conclude that this case is unique and represents a forme fruste of the Cronkhite-Canada syndrome. A complicating feature was the presence of an opportunistic cytomegalovirus infection of the gastrointestinal tract and lungs.", "contents": "Superficial cystic gastritis with alopecia. A forme fruste of the Cronkhite-Canada syndrome. The Cronkhite-Canada syndrome is a rare and often fatal condition. A case of superficial cystic gastritis was suspected on peroral gastric biopsy and was later confirmed at autopsy. The selective involvement of the stomach together with the presence of alopecia leads us to conclude that this case is unique and represents a forme fruste of the Cronkhite-Canada syndrome. A complicating feature was the presence of an opportunistic cytomegalovirus infection of the gastrointestinal tract and lungs."}
{"id": "PMID:195554", "title": "C bodies and R bodies in the epithelial cells of normal and diseased human rectum.", "content": "Small spherical, extracellular bodies (C bodies) measuring 20 to 80 nm in diameter and enclosed by a trilaminar membrane 7 nm wide surrounded the microvilli of human rectal epithelial cells. Similar bodies were observed within membrane-bound vesicles (R bodies) in the apical cytoplasm. The C bodies associated with the mature epithelial cells of the luminal surface were more numerous than those associated with the immature cells of the crypts, where the R bodies predominated. A decreased number of C bodies was observed in ulcerative colitis. We concluded that the membrane-bound C bodies surrounding the microvilli were cellular in origin and arose from R bodies within the cytoplasm of the rectal epithelial cells.", "contents": "C bodies and R bodies in the epithelial cells of normal and diseased human rectum. Small spherical, extracellular bodies (C bodies) measuring 20 to 80 nm in diameter and enclosed by a trilaminar membrane 7 nm wide surrounded the microvilli of human rectal epithelial cells. Similar bodies were observed within membrane-bound vesicles (R bodies) in the apical cytoplasm. The C bodies associated with the mature epithelial cells of the luminal surface were more numerous than those associated with the immature cells of the crypts, where the R bodies predominated. A decreased number of C bodies was observed in ulcerative colitis. We concluded that the membrane-bound C bodies surrounding the microvilli were cellular in origin and arose from R bodies within the cytoplasm of the rectal epithelial cells."}
{"id": "PMID:195555", "title": "Fine structure of Sertoli and Leydig cells in azoospermic human testis.", "content": "Testicular biopsy specimens taken from seven patients with azoospermia were studied by electron microscopy. We considered the possibility of a relationship between the annulate lamellae in the Sertoli cells and azoospermia. In the Leydig cells, we observed intranuclear and intracytoplasmic paracrystalline inclusions and considered their relationship with the Reinke crystalloid.", "contents": "Fine structure of Sertoli and Leydig cells in azoospermic human testis. Testicular biopsy specimens taken from seven patients with azoospermia were studied by electron microscopy. We considered the possibility of a relationship between the annulate lamellae in the Sertoli cells and azoospermia. In the Leydig cells, we observed intranuclear and intracytoplasmic paracrystalline inclusions and considered their relationship with the Reinke crystalloid."}
{"id": "PMID:195557", "title": "Tendon reflex latencies in the upper extremity.", "content": "This study was aimed at establishing a baseline for the latency values of the biceps-brachii, triceps-brachii and brachioradialis tendon reflexes from the moment of elicitation by percussion of the tendon, to the appearance of the muscle action potential. The percussion hammer triggered the electronic sweep on the electromyograph oscilloscope, showing latency to the onset of the potential. Standard skin electrodes were used. Certain precautions were taken to avoid artifacts caused by skin movement. Thirty normal volunteer subjects, between the ages of 17 and 55 years, were examined. Biceps reflex latency values varied between 9 and 14 msec; with a mode of 11 msec and an average of 11 msec. Triceps latency values varied between 9 and 13 msec; with a mode of 11 msec and an average of 10 msec, and brachioradialis latency values varied between 13 and 20 msec, with a mode of 16 msec and an average of 16 msec.", "contents": "Tendon reflex latencies in the upper extremity. This study was aimed at establishing a baseline for the latency values of the biceps-brachii, triceps-brachii and brachioradialis tendon reflexes from the moment of elicitation by percussion of the tendon, to the appearance of the muscle action potential. The percussion hammer triggered the electronic sweep on the electromyograph oscilloscope, showing latency to the onset of the potential. Standard skin electrodes were used. Certain precautions were taken to avoid artifacts caused by skin movement. Thirty normal volunteer subjects, between the ages of 17 and 55 years, were examined. Biceps reflex latency values varied between 9 and 14 msec; with a mode of 11 msec and an average of 11 msec. Triceps latency values varied between 9 and 13 msec; with a mode of 11 msec and an average of 10 msec, and brachioradialis latency values varied between 13 and 20 msec, with a mode of 16 msec and an average of 16 msec."}
{"id": "PMID:195558", "title": "Bacteriology of the human biliary tract and the duodenum.", "content": "Using the modern anaerobic transport media and meticulous culture techniques, 74 patients undergoing biliary tract surgery were studied. The biliary system was found to be sterile in 58 patients (78%). Fifteen patients had 35 isolates of aerobic and facultative bacteria. The most common ones were Klebsiella, Enterococcus, and Escherichia coli. The only anaerobe isolated was Clostridium perfringens. Eight of 17 patients (47%) with acute cholecystitis and five of 49 patients (10%) with chronic cholecystitis, harbored bacteria in the biliary system. This study suggests that anaerobes are rare in the human biliary system; therefore, if antibiotic therapy is considered, aerobic coverage should suffice.", "contents": "Bacteriology of the human biliary tract and the duodenum. Using the modern anaerobic transport media and meticulous culture techniques, 74 patients undergoing biliary tract surgery were studied. The biliary system was found to be sterile in 58 patients (78%). Fifteen patients had 35 isolates of aerobic and facultative bacteria. The most common ones were Klebsiella, Enterococcus, and Escherichia coli. The only anaerobe isolated was Clostridium perfringens. Eight of 17 patients (47%) with acute cholecystitis and five of 49 patients (10%) with chronic cholecystitis, harbored bacteria in the biliary system. This study suggests that anaerobes are rare in the human biliary system; therefore, if antibiotic therapy is considered, aerobic coverage should suffice."}
{"id": "PMID:195559", "title": "Chromatography by silica-gel chromatobars. Prospects of its application in the field of forensic toxicology.", "content": "A new type of chromatographic column of silica gel 20 mm in diameter and 180 mm long has been investigated in the field of forensic analytical toxicology. In order to evaluate the usefulness of chromatobars in isolating organic compounds from biological extracts, sodium phenyl-ethyl-barbiturate, atropine, morphine and strychnine were added to the aqueous extract obtained with Stas-Otto's isolation method. Afterwards the residues of the acidic ether extract, alkaline ether extract and alkaline chloroform extract, were chromatographed on chromatobar. This chromatographic device seems able to avoid the drawbacks and limitations of paper and thin-layer chromatography, mainly from the preparative aspect. The method is particularly advantageous in analysing the whole extract obtained with the Stas-Otto process, without bringing about its partition, especially when slight traces of toxic substances are present.", "contents": "Chromatography by silica-gel chromatobars. Prospects of its application in the field of forensic toxicology. A new type of chromatographic column of silica gel 20 mm in diameter and 180 mm long has been investigated in the field of forensic analytical toxicology. In order to evaluate the usefulness of chromatobars in isolating organic compounds from biological extracts, sodium phenyl-ethyl-barbiturate, atropine, morphine and strychnine were added to the aqueous extract obtained with Stas-Otto's isolation method. Afterwards the residues of the acidic ether extract, alkaline ether extract and alkaline chloroform extract, were chromatographed on chromatobar. This chromatographic device seems able to avoid the drawbacks and limitations of paper and thin-layer chromatography, mainly from the preparative aspect. The method is particularly advantageous in analysing the whole extract obtained with the Stas-Otto process, without bringing about its partition, especially when slight traces of toxic substances are present."}
{"id": "PMID:195561", "title": "[Acute leukemia and generalized cytomegaly in a 10-year-old boy].", "content": "A case of acute myelomonocytic leukemia in a 10-year-old boy who received massive cytostatic therapy is described. At autopsy a picture of therapeutically determined pathomorphism and cytostatic disease with generalized cytomegalia and terminal staphylococcal sepsis was revealed. Multiple thrombosis of major venous trunks, necroses of the cecum and subtotal necrosis of the spleen were observed; this apparently was associated with generalized cytomegalia and massive cytostatic therapy. Peculiar features of the case were dystrophic changes in cytomegalic cells subjected to necrobiosis, which, probably, was due to cytostatic therapy.", "contents": "[Acute leukemia and generalized cytomegaly in a 10-year-old boy]. A case of acute myelomonocytic leukemia in a 10-year-old boy who received massive cytostatic therapy is described. At autopsy a picture of therapeutically determined pathomorphism and cytostatic disease with generalized cytomegalia and terminal staphylococcal sepsis was revealed. Multiple thrombosis of major venous trunks, necroses of the cecum and subtotal necrosis of the spleen were observed; this apparently was associated with generalized cytomegalia and massive cytostatic therapy. Peculiar features of the case were dystrophic changes in cytomegalic cells subjected to necrobiosis, which, probably, was due to cytostatic therapy."}
{"id": "PMID:195562", "title": "Recurrent encephalitis with elevated titers for herpes simplex.", "content": "An 8-year-old boy was seen on two occasions 14 months apart with signs and symptoms of encephalitis. The clinical course and laboratory studies were highly suggesive of herpes simplex infection during both episodes.", "contents": "Recurrent encephalitis with elevated titers for herpes simplex. An 8-year-old boy was seen on two occasions 14 months apart with signs and symptoms of encephalitis. The clinical course and laboratory studies were highly suggesive of herpes simplex infection during both episodes."}
{"id": "PMID:195563", "title": "Diagnostic value of crossed vs uncrossed acoustic reflexes: eighth nerve and brain stem disorders.", "content": "Acoustic reflexes to crossed (sound in one ear; probe in opposite ear) and uncrossed (sound and probe in the same ear) stimulation were obtained from 17 patients with eighth nerve or brain stem disorders and 20 normal control subjects. Comparison of crossed and uncrossed reflex thresholds provided an important diagnostic tool for differentiating the eighth nerve from the brain stem site. Egihth nerve disorders were usually characterized by diagonal reflex patterns. In contrast, brain stem disorders were usually characterized by horizontal reflex patterns. Detailed evaluation of the reflex time course in two selected patients with intra-axial brain stem disorder showed unusual abnormalities in the crossed acoustic reflex.", "contents": "Diagnostic value of crossed vs uncrossed acoustic reflexes: eighth nerve and brain stem disorders. Acoustic reflexes to crossed (sound in one ear; probe in opposite ear) and uncrossed (sound and probe in the same ear) stimulation were obtained from 17 patients with eighth nerve or brain stem disorders and 20 normal control subjects. Comparison of crossed and uncrossed reflex thresholds provided an important diagnostic tool for differentiating the eighth nerve from the brain stem site. Egihth nerve disorders were usually characterized by diagonal reflex patterns. In contrast, brain stem disorders were usually characterized by horizontal reflex patterns. Detailed evaluation of the reflex time course in two selected patients with intra-axial brain stem disorder showed unusual abnormalities in the crossed acoustic reflex."}
{"id": "PMID:195564", "title": "The fine structure of lipofuscin in the human inner ear.", "content": "Lipofuscin inclusions in the human membranous labyrinth were studied by electron microscopy. Lipofuscin is morphologically an irregularly shaped, membrane-bound inclusion consisting of an electron-dense structure. The most common component was a fine, granular, osmiophilic substance which was always associated with a homogenous, spherical structure resembling a lipid droplet. The combination of these two components was frequently observed in the human inner ear. Distended inclusions containing lipofuscin components were also observed within the supporting cells, saccular, utricular and ampullar wall, the epithelial cells of the transitional zone and in the dark cells. Lipofuscin is closely associated with lysosome and is known to accumulate in the tissue as a result of aging. The high lysosomal activity possibly may result in lipofuscin formation in the human inner ears. Also some other unknown metabolic conditions may provide the deposits of lipofuscin.", "contents": "The fine structure of lipofuscin in the human inner ear. Lipofuscin inclusions in the human membranous labyrinth were studied by electron microscopy. Lipofuscin is morphologically an irregularly shaped, membrane-bound inclusion consisting of an electron-dense structure. The most common component was a fine, granular, osmiophilic substance which was always associated with a homogenous, spherical structure resembling a lipid droplet. The combination of these two components was frequently observed in the human inner ear. Distended inclusions containing lipofuscin components were also observed within the supporting cells, saccular, utricular and ampullar wall, the epithelial cells of the transitional zone and in the dark cells. Lipofuscin is closely associated with lysosome and is known to accumulate in the tissue as a result of aging. The high lysosomal activity possibly may result in lipofuscin formation in the human inner ears. Also some other unknown metabolic conditions may provide the deposits of lipofuscin."}
{"id": "PMID:195568", "title": "Increased responsiveness of heart rate to beta-adrenergic stimulation in cold-adapted rats.", "content": "The responsiveness of heart rate of cold-adapted rats (10-12 weeks, 5degrees C.) to a specific beta-adrenergic agonist was studied. Two hours after removal from cold, s.c. administration of  l-isoproterenol (4, 8, or 16 microng/kg body weight) to female rats was accompanied by a greater responsiveness in cold-treated animals. The increase in heart rate of cold-treated rats above that of warm-adapted controls was related linearly to the dose of isoproterenol administered. An increased sensitivity of heart rate to isoproterenol (8 microng/kg body weight, s.c.) was also observed in male, cold-treated rats. The results suggest that adaptation to cold air is accompanied by increased beta-adrenergic responsiveness in rats.", "contents": "Increased responsiveness of heart rate to beta-adrenergic stimulation in cold-adapted rats. The responsiveness of heart rate of cold-adapted rats (10-12 weeks, 5degrees C.) to a specific beta-adrenergic agonist was studied. Two hours after removal from cold, s.c. administration of  l-isoproterenol (4, 8, or 16 microng/kg body weight) to female rats was accompanied by a greater responsiveness in cold-treated animals. The increase in heart rate of cold-treated rats above that of warm-adapted controls was related linearly to the dose of isoproterenol administered. An increased sensitivity of heart rate to isoproterenol (8 microng/kg body weight, s.c.) was also observed in male, cold-treated rats. The results suggest that adaptation to cold air is accompanied by increased beta-adrenergic responsiveness in rats."}
{"id": "PMID:195569", "title": "Actions of cholinergic agonist and antagonists on the adrenocortical response of basal, hypoxic, and hypercapnic rats.", "content": "Cholinergic neuronal influences on the function of male rat's hypothalamo-hypophyseal-adrenocortical (HHA) system both during basal and stressful situations (hypoxia and hypercapnia) were  investigated using a cholinergic agonist (eserine) and  antagonists (atropine, methyl atropine, mecamylamine and 4-(1-naphthylvinyl) pyridine). The results indicate that the transmitter, acetylcholine (ACh), plays a partial role in the regulation of the HHA system. The muscarinic (m) effects of ACh were stimulatory peripherally and inhibitory centrally. The nicotinic (n) effects were stimulatory and possibly affected the HHA system by inhibiting the central m-inputs. The cholinergic regulation of the HHA system for both non-stressed and hypercapnic animals is probably mediated via a common nm-cholinergic pathway.", "contents": "Actions of cholinergic agonist and antagonists on the adrenocortical response of basal, hypoxic, and hypercapnic rats. Cholinergic neuronal influences on the function of male rat's hypothalamo-hypophyseal-adrenocortical (HHA) system both during basal and stressful situations (hypoxia and hypercapnia) were  investigated using a cholinergic agonist (eserine) and  antagonists (atropine, methyl atropine, mecamylamine and 4-(1-naphthylvinyl) pyridine). The results indicate that the transmitter, acetylcholine (ACh), plays a partial role in the regulation of the HHA system. The muscarinic (m) effects of ACh were stimulatory peripherally and inhibitory centrally. The nicotinic (n) effects were stimulatory and possibly affected the HHA system by inhibiting the central m-inputs. The cholinergic regulation of the HHA system for both non-stressed and hypercapnic animals is probably mediated via a common nm-cholinergic pathway."}
{"id": "PMID:195572", "title": "Adenylate kinase 2, a mitochondrial enzyme.", "content": "The subcellular compartmentalization of the isoenzymes of ATP:AMP phosphotransferase (adenylate kinase) was analyzed in HeLa cells, RAG cells, and RAG-human hybrids that express human AK-2. In HeLa cells and in the hybrids, human AK-2 was present in a mitochemical fraction prepared from cell extracts and in mitochondria purified by density gradient centrifugation. Human AK-1 was, as expected, distributed in the soluble cytoplasmic fraction of the cells. The rodent isozymes which are homologous to human AK-1 and AK-2 have been determined.", "contents": "Adenylate kinase 2, a mitochondrial enzyme. The subcellular compartmentalization of the isoenzymes of ATP:AMP phosphotransferase (adenylate kinase) was analyzed in HeLa cells, RAG cells, and RAG-human hybrids that express human AK-2. In HeLa cells and in the hybrids, human AK-2 was present in a mitochemical fraction prepared from cell extracts and in mitochondria purified by density gradient centrifugation. Human AK-1 was, as expected, distributed in the soluble cytoplasmic fraction of the cells. The rodent isozymes which are homologous to human AK-1 and AK-2 have been determined."}
{"id": "PMID:195573", "title": "Rabbit tissue peptidases that hydrolyse the peptide hormone bradykinin. Differences in enzymic properties and concentration in rabbit tissues.", "content": "The distribution and properties of neutral peptidases acting on the peptide hormone bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) were determined in several rabbit tissues. The supernatant and particulate fractions prepared from tissue homogenates (25000g for 60min) were studied. Bradykinin inactivation (kininase activity) was measured by bioassay with the isolated guinea-pig ileum. The sites of peptide-bond cleavage were determined in the amino acid analyser, which permits detection and measurement of amino acids and peptides derived from bradykinin. The results indicate that kininases are present in a wide range of concentrations in different tissues, kidney and lung having the most activity. Kininases present in different tissues were distinguished on the basis of sensitivity to the effects of EDTA, dithiothreitol and ZnCl2 and by the site of peptide-bond hydrolysis in bradykinin.", "contents": "Rabbit tissue peptidases that hydrolyse the peptide hormone bradykinin. Differences in enzymic properties and concentration in rabbit tissues. The distribution and properties of neutral peptidases acting on the peptide hormone bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) were determined in several rabbit tissues. The supernatant and particulate fractions prepared from tissue homogenates (25000g for 60min) were studied. Bradykinin inactivation (kininase activity) was measured by bioassay with the isolated guinea-pig ileum. The sites of peptide-bond cleavage were determined in the amino acid analyser, which permits detection and measurement of amino acids and peptides derived from bradykinin. The results indicate that kininases are present in a wide range of concentrations in different tissues, kidney and lung having the most activity. Kininases present in different tissues were distinguished on the basis of sensitivity to the effects of EDTA, dithiothreitol and ZnCl2 and by the site of peptide-bond hydrolysis in bradykinin."}
{"id": "PMID:195574", "title": "Generation of hydrogen peroxide, superoxide and hydroxyl radicals during the oxidation of dihydroxyfumaric acid by peroxidase.", "content": "1. Dihydroxyfumarate slowly autoxidizes at pH6. This reaction is inhibited by superoxide dismutase but not by EDTA. Mn2+ catalyses dihydroxyfumarate oxidation by reacting with O2 leads to to form Mn3+, which seems to oxidize dihydrofumarate rapidly. Cu2+ also catalyses dihydroxyfumarate oxidation, but by a mechanism that does not involve O2 leads to. 2. Peroxidase catalyses oxidation of dihydroxyfumarate at pH6; addition of H2O2 does not increase the rate. Experiments with superoxide dismutase and catalase suggest that there are two types of oxidation taking place: an enzymic, H2O2-dependent oxidation of dihydroxyfumarate by peroxidase, and a non-enzymic reaction involving oxidation of dihydroxyfumarate by O2 leads to. The latter accounts for most of the observed oxidation of dihydroxyfumarate. 3. During dihydroxyfumarate oxidation, most peroxidase is present as compound III, and the enzymic oxidation may be limited by the low rate of breakdown of this compound. 4. Addition of p-coumaric acid to the peroxidase/dihydroxyfumarate system increases the rate of dihydroxyfumarate oxidation, which is now stimulated by addition of H2O2, and is more sensitive to inhibition by catalase but less sensitive to superoxide dismutase. Compound III is decomposed in the presence of p-coumaric acid. p-Hydroxybenzoate has similar, but much smaller, effects on dihydroxyfumarate oxidation. However, salicylate affects neither the rate nor the mechanism of dihydroxyfumarate oxidation. 5. p-Hydroxybenzoate, salicylate and p-coumarate are hydroxylated by the peroxidase/dihydroxyfumarate system. Experiments using scavengers of hydroxyl radicals shown that OH is required. Ability to increase dihydroxyfumarate oxidation is not necessary for hydroxylation to occur.", "contents": "Generation of hydrogen peroxide, superoxide and hydroxyl radicals during the oxidation of dihydroxyfumaric acid by peroxidase. 1. Dihydroxyfumarate slowly autoxidizes at pH6. This reaction is inhibited by superoxide dismutase but not by EDTA. Mn2+ catalyses dihydroxyfumarate oxidation by reacting with O2 leads to to form Mn3+, which seems to oxidize dihydrofumarate rapidly. Cu2+ also catalyses dihydroxyfumarate oxidation, but by a mechanism that does not involve O2 leads to. 2. Peroxidase catalyses oxidation of dihydroxyfumarate at pH6; addition of H2O2 does not increase the rate. Experiments with superoxide dismutase and catalase suggest that there are two types of oxidation taking place: an enzymic, H2O2-dependent oxidation of dihydroxyfumarate by peroxidase, and a non-enzymic reaction involving oxidation of dihydroxyfumarate by O2 leads to. The latter accounts for most of the observed oxidation of dihydroxyfumarate. 3. During dihydroxyfumarate oxidation, most peroxidase is present as compound III, and the enzymic oxidation may be limited by the low rate of breakdown of this compound. 4. Addition of p-coumaric acid to the peroxidase/dihydroxyfumarate system increases the rate of dihydroxyfumarate oxidation, which is now stimulated by addition of H2O2, and is more sensitive to inhibition by catalase but less sensitive to superoxide dismutase. Compound III is decomposed in the presence of p-coumaric acid. p-Hydroxybenzoate has similar, but much smaller, effects on dihydroxyfumarate oxidation. However, salicylate affects neither the rate nor the mechanism of dihydroxyfumarate oxidation. 5. p-Hydroxybenzoate, salicylate and p-coumarate are hydroxylated by the peroxidase/dihydroxyfumarate system. Experiments using scavengers of hydroxyl radicals shown that OH is required. Ability to increase dihydroxyfumarate oxidation is not necessary for hydroxylation to occur."}
{"id": "PMID:195575", "title": "Characterization of serum lipoproteins of the shark Centrophorus squamous.", "content": "1. Blood serum from the shark Centrophorus squamosus (Bonnaterre) was shown to contain VLD (very-low-density), LD (low-density) and HD (high-density) lipoproteins. 2. In shape, size and general physical properties, these lipoproteins were very similar to those described for other animals. The VLD lipoproteins were the major components of the mixture, and HD lipoproteins were present at the lowest amount. 3. In addition to the usual lipid components, the shark lipoproteins also contain substantial amounts of hydrocarbon, probably mainly squalene, and monoalkyldiacylglycerols. Only trace amounts of wax ester were detected. 4. The protein moiety of the VLD and LD lipoproteins contained a component which, in its solubility and electrophoretic properties, molecular weight and amino acid composition, resembled the B apolipoprotein of man and other mammals. This accounted for a large part of the total shark apolipoprotein. 5. There were also present smaller amounts of proteins which were soluble in 8M-urea. In their electrophoretic mobility on basic polyacrylamide gel, some of these were like the A and C apoproteins of man. 6. The electrophoretic distribution of the soluble proteins from the VLD and LD lipoproteins resembled that in higher mammals, but in the HD lipoproteins the similarity was less.", "contents": "Characterization of serum lipoproteins of the shark Centrophorus squamous. 1. Blood serum from the shark Centrophorus squamosus (Bonnaterre) was shown to contain VLD (very-low-density), LD (low-density) and HD (high-density) lipoproteins. 2. In shape, size and general physical properties, these lipoproteins were very similar to those described for other animals. The VLD lipoproteins were the major components of the mixture, and HD lipoproteins were present at the lowest amount. 3. In addition to the usual lipid components, the shark lipoproteins also contain substantial amounts of hydrocarbon, probably mainly squalene, and monoalkyldiacylglycerols. Only trace amounts of wax ester were detected. 4. The protein moiety of the VLD and LD lipoproteins contained a component which, in its solubility and electrophoretic properties, molecular weight and amino acid composition, resembled the B apolipoprotein of man and other mammals. This accounted for a large part of the total shark apolipoprotein. 5. There were also present smaller amounts of proteins which were soluble in 8M-urea. In their electrophoretic mobility on basic polyacrylamide gel, some of these were like the A and C apoproteins of man. 6. The electrophoretic distribution of the soluble proteins from the VLD and LD lipoproteins resembled that in higher mammals, but in the HD lipoproteins the similarity was less."}
{"id": "PMID:195576", "title": "A comparison of the association of yeast phosphoglycerate mutase (EC2.7.5.3) with that of haemoglobin. An ultracentrifuge study.", "content": "1. Previous work showed that yeast phosphoglycerate mutase (EC 2.7.5.3) has a mol.wt. of between 107000 and 110000. Preliminary examination showed that at dilutions less than 0.1 g/1 the enzyme dissociated into its subunits. 2. This dissociation was quantitatively examined by both equilibrium and velocity centrifugation. 3. The mathematical analysis of the equilibrium records was tested against oxyhaemoglobin in a variety of ionic strengths and at two temperatures. 4. The estimated L2,4 (interaction coefficient) for oxyhaemoglobin generally agreed with published values except at 6 degrees C in 0.9 M-NaCl, when it was 2.5 times larger than the published value. 5. Statistical analysis of ultracentrifugal-equilibrium experiments showed that the predominant reaction for phosphoglycerate mutase was monomer in equilibrium tetramer, to give an L1,4 of 40.3+/-23.4 (S.D.)1(3)-g(-3) at 20 degrees C. Decreasing the temperature decreased the association to given an enthalpy of between 40 and 60kJ/mol. 6. Analysis of velocity experiments carried out with concentrations varying from 0.3 to 17 g/1 gave an L1,4 of 3111(3)-g(-3). Incorporating errors from estimating S20,w into the analysis showed that this estimate could range from 893 to 1421(3)-g(-3). 7. The concentration-dependence of S20,w was 0.95 litre-g-1 and s020,w for the tetramer was 66.9ps. 8. These results are discussed in relation to the activity of the enzyme.", "contents": "A comparison of the association of yeast phosphoglycerate mutase (EC2.7.5.3) with that of haemoglobin. An ultracentrifuge study. 1. Previous work showed that yeast phosphoglycerate mutase (EC 2.7.5.3) has a mol.wt. of between 107000 and 110000. Preliminary examination showed that at dilutions less than 0.1 g/1 the enzyme dissociated into its subunits. 2. This dissociation was quantitatively examined by both equilibrium and velocity centrifugation. 3. The mathematical analysis of the equilibrium records was tested against oxyhaemoglobin in a variety of ionic strengths and at two temperatures. 4. The estimated L2,4 (interaction coefficient) for oxyhaemoglobin generally agreed with published values except at 6 degrees C in 0.9 M-NaCl, when it was 2.5 times larger than the published value. 5. Statistical analysis of ultracentrifugal-equilibrium experiments showed that the predominant reaction for phosphoglycerate mutase was monomer in equilibrium tetramer, to give an L1,4 of 40.3+/-23.4 (S.D.)1(3)-g(-3) at 20 degrees C. Decreasing the temperature decreased the association to given an enthalpy of between 40 and 60kJ/mol. 6. Analysis of velocity experiments carried out with concentrations varying from 0.3 to 17 g/1 gave an L1,4 of 3111(3)-g(-3). Incorporating errors from estimating S20,w into the analysis showed that this estimate could range from 893 to 1421(3)-g(-3). 7. The concentration-dependence of S20,w was 0.95 litre-g-1 and s020,w for the tetramer was 66.9ps. 8. These results are discussed in relation to the activity of the enzyme."}
{"id": "PMID:195577", "title": "The reduction of Pseudomonas cytochrome c551 oxidase by chromous ions.", "content": "The reduction  of cytochrome c551 oxidase from Pseudomonas aeruginosa by Cr2+ ions was followed in the stopped-flow apparatus at a number of wavelengths. The c-haem reduction proceeded in a biphasic fashion with second-order rate constants of 2.6 X 10(5)M-1-S-1 and 4.8 X 10(4)M-1-S-1 at 25 degrees C, whereas the biphasic reduction of the d1-haem appeared to be independent of reductant concentration with rate constants of approx. 1.0S-1 and 0.25S-1 respectively. The kinetically determined difference spectra (reduced minus oxidized) for the c- and d1-haems are presented.", "contents": "The reduction of Pseudomonas cytochrome c551 oxidase by chromous ions. The reduction  of cytochrome c551 oxidase from Pseudomonas aeruginosa by Cr2+ ions was followed in the stopped-flow apparatus at a number of wavelengths. The c-haem reduction proceeded in a biphasic fashion with second-order rate constants of 2.6 X 10(5)M-1-S-1 and 4.8 X 10(4)M-1-S-1 at 25 degrees C, whereas the biphasic reduction of the d1-haem appeared to be independent of reductant concentration with rate constants of approx. 1.0S-1 and 0.25S-1 respectively. The kinetically determined difference spectra (reduced minus oxidized) for the c- and d1-haems are presented."}
{"id": "PMID:195578", "title": "Aldehyde dehydrogenase in 2-acetamidofluorene-induced rat hepatomas. Ontogeny and evidence that the new isoenzymes are not due to normal gene de-repression.", "content": "The pre- and post-natal ontogeny of Sprague-Dawley rat liver aldehyde dehydrogenase [aldehyde-NAD(P)(+) oxidoreductase, EC 1.2.1.5] is described. At no time in its ontogenetic development does normal liver aldehyde dehydrogenase exhibit any of the characteristics of a series of unique aldehyde dehydrogenases that can be isolated from 2-acetamidofluorene-induced rat hepatomas. Enzyme activity is first detectable in 15-day foetal liver and gradually increases throughout pre- and post-natal development until adult activities are attained by day 49 after birth. Electrophoretically, normal aldehyde dehydrogenase, throughout its ontogeny, exists as the same single isoenzyme found in normal adult liver. Isoelectric points for two normal liver isoenzymes demonstrable by isoelectric focusing are pH5.9 and 6.0. The immunochemical properties of aldehyde dehydrogenase during its ontogeny are identical with those of normal adult liver aldehyde dehydrogenase when tested against anti-(hepatoma aldehyde dehydrogenase) serum in Ouchterlony double-diffusion tests. The results indicate that the hepatoma-specific aldehyde dehydrogenases are not the result of the de-repression of genes normally repressed in adult rat liver or in some other adult tissue.", "contents": "Aldehyde dehydrogenase in 2-acetamidofluorene-induced rat hepatomas. Ontogeny and evidence that the new isoenzymes are not due to normal gene de-repression. The pre- and post-natal ontogeny of Sprague-Dawley rat liver aldehyde dehydrogenase [aldehyde-NAD(P)(+) oxidoreductase, EC 1.2.1.5] is described. At no time in its ontogenetic development does normal liver aldehyde dehydrogenase exhibit any of the characteristics of a series of unique aldehyde dehydrogenases that can be isolated from 2-acetamidofluorene-induced rat hepatomas. Enzyme activity is first detectable in 15-day foetal liver and gradually increases throughout pre- and post-natal development until adult activities are attained by day 49 after birth. Electrophoretically, normal aldehyde dehydrogenase, throughout its ontogeny, exists as the same single isoenzyme found in normal adult liver. Isoelectric points for two normal liver isoenzymes demonstrable by isoelectric focusing are pH5.9 and 6.0. The immunochemical properties of aldehyde dehydrogenase during its ontogeny are identical with those of normal adult liver aldehyde dehydrogenase when tested against anti-(hepatoma aldehyde dehydrogenase) serum in Ouchterlony double-diffusion tests. The results indicate that the hepatoma-specific aldehyde dehydrogenases are not the result of the de-repression of genes normally repressed in adult rat liver or in some other adult tissue."}
{"id": "PMID:195579", "title": "Adenosine as a constituent of the brain and of isolated cerebral tissues, and its relationship to the generation of adenosine 3':5'-cyclic monophosphate.", "content": "1. Adenosine was determined in rapidly frozen rat and guinea-pig brain and in guinea-pig cerebral tissues after incubation in vitro. Adenosine concentrations were approx. 2nmol/g wet wt. in frozen tissue, diminished at room temperature, and returned to 2nmol/g on incubation in oxygenated glucose/salines. 2. Superfusion with noradrenaline then increased the tissue's adenosine concentration 2.5-fold, and hypoxia caused an 8-fold increase. 3. Electrical stimulation alone or in the presence of noradrenaline or histamine increased the tissue's adenosine and cyclic AMP, but adenosine concentrations reached their peak later and were maintained for longer than those of cyclic AMP. 4. Superfusion with l-glutamate with and without electrical excitation raised adenosine concentrations to 15-34nmol/g. The increases in cyclic AMP on electrical stimulation, superfusion with glutamate or a combination of these treatments were diminished by addition of adenosine deaminase or theophylline. 5. It is concluded that adenosine can be produced endogenously in cerebral systems, in sufficient concentrations to accelerate an adenosine-activated adenylate cyclase, and by this route can contribute to the cerebral actions of electrical stimulation and of the neurohumoral agents. In certain instances cyclic AMP as substrate contributes to an increase in adenosine.", "contents": "Adenosine as a constituent of the brain and of isolated cerebral tissues, and its relationship to the generation of adenosine 3':5'-cyclic monophosphate. 1. Adenosine was determined in rapidly frozen rat and guinea-pig brain and in guinea-pig cerebral tissues after incubation in vitro. Adenosine concentrations were approx. 2nmol/g wet wt. in frozen tissue, diminished at room temperature, and returned to 2nmol/g on incubation in oxygenated glucose/salines. 2. Superfusion with noradrenaline then increased the tissue's adenosine concentration 2.5-fold, and hypoxia caused an 8-fold increase. 3. Electrical stimulation alone or in the presence of noradrenaline or histamine increased the tissue's adenosine and cyclic AMP, but adenosine concentrations reached their peak later and were maintained for longer than those of cyclic AMP. 4. Superfusion with l-glutamate with and without electrical excitation raised adenosine concentrations to 15-34nmol/g. The increases in cyclic AMP on electrical stimulation, superfusion with glutamate or a combination of these treatments were diminished by addition of adenosine deaminase or theophylline. 5. It is concluded that adenosine can be produced endogenously in cerebral systems, in sufficient concentrations to accelerate an adenosine-activated adenylate cyclase, and by this route can contribute to the cerebral actions of electrical stimulation and of the neurohumoral agents. In certain instances cyclic AMP as substrate contributes to an increase in adenosine."}
{"id": "PMID:195580", "title": "Endogenous phosphorylation of microsomal proteins in bovine corpus luteum. Tenfold activation by adenosine 3':5'-cyclic monophosphate.", "content": "Free ribosomes and a smooth-microsomal fraction were prepared from bovine corpus luteum. Both preparations will self-phosphorylate when incubated with Mg(2+) and ATP, but at low concentrations of Mg(2+) and ATP the self-phosphorylation of the smooth-microsomal fraction was much more dependent on cyclic AMP than was that of free ribosomes, stimulation by the nucleotide being up to 10-fold in the former case. The self-phosphorylation of the smooth-microsomal fraction was studied further. The reaction bears similarities to that brought about by soluble cyclic AMP-dependent protein kinase, being inhibited by Ca(2+) and the heat-stable inhibitor protein from skeletal muscle. Cyclic GMP will activate the reaction at concentrations higher than those required for full activation by cyclic AMP. In the presence of cyclic AMP, phosphate bound to protein is found almost exclusively as phosphoserine. Several proteins are phosphorylated, as judged by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, and the phosphorylation of all of them is markedly stimulated by cyclic AMP. If the reaction is carried out at high concentrations of Mg(2+) and ATP, a distinct cyclic AMP-independent phosphorylation is observed. This activity is not inhibited by the heat-stable inhibitor protein, and phosphate is found esterified with both threonine and serine residues.", "contents": "Endogenous phosphorylation of microsomal proteins in bovine corpus luteum. Tenfold activation by adenosine 3':5'-cyclic monophosphate. Free ribosomes and a smooth-microsomal fraction were prepared from bovine corpus luteum. Both preparations will self-phosphorylate when incubated with Mg(2+) and ATP, but at low concentrations of Mg(2+) and ATP the self-phosphorylation of the smooth-microsomal fraction was much more dependent on cyclic AMP than was that of free ribosomes, stimulation by the nucleotide being up to 10-fold in the former case. The self-phosphorylation of the smooth-microsomal fraction was studied further. The reaction bears similarities to that brought about by soluble cyclic AMP-dependent protein kinase, being inhibited by Ca(2+) and the heat-stable inhibitor protein from skeletal muscle. Cyclic GMP will activate the reaction at concentrations higher than those required for full activation by cyclic AMP. In the presence of cyclic AMP, phosphate bound to protein is found almost exclusively as phosphoserine. Several proteins are phosphorylated, as judged by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, and the phosphorylation of all of them is markedly stimulated by cyclic AMP. If the reaction is carried out at high concentrations of Mg(2+) and ATP, a distinct cyclic AMP-independent phosphorylation is observed. This activity is not inhibited by the heat-stable inhibitor protein, and phosphate is found esterified with both threonine and serine residues."}
{"id": "PMID:195581", "title": "Phosphatidylinositol-degrading enzymes in liver lysosomes.", "content": "The major pathway by which liver lysosomal enzymes degrade phosphatidylinositol is through an EDTA-insensitive formation of phosphorylinositol. This is in distinct contrast with the Ca2+-dependent production of phosphorylinositol from phosphatidylinositol, which is located in the cytosol. Lysosomal enzymes can also totally deacylate phosphatidylinositol, producing glycerophosphorylinositol.", "contents": "Phosphatidylinositol-degrading enzymes in liver lysosomes. The major pathway by which liver lysosomal enzymes degrade phosphatidylinositol is through an EDTA-insensitive formation of phosphorylinositol. This is in distinct contrast with the Ca2+-dependent production of phosphorylinositol from phosphatidylinositol, which is located in the cytosol. Lysosomal enzymes can also totally deacylate phosphatidylinositol, producing glycerophosphorylinositol."}
{"id": "PMID:195582", "title": "Net activity of phospholipase A2 in brain and the lack of stimulation of the phospholipase A2-acylation stem.", "content": "Certain observations reported previously from this laboratory have not proved reproducible. These are (1) the relatively rapid hydrolysis of added phosphatidylcholine by phospholipase A2 of tissue from the cerebral cortex of the guinea pig and (2) the stimulation by 10 micron-noradrenaline and by 1.0nM-cyclic AMP of the phospholipase A2-acylation system of isolated synaptic membranes.", "contents": "Net activity of phospholipase A2 in brain and the lack of stimulation of the phospholipase A2-acylation stem. Certain observations reported previously from this laboratory have not proved reproducible. These are (1) the relatively rapid hydrolysis of added phosphatidylcholine by phospholipase A2 of tissue from the cerebral cortex of the guinea pig and (2) the stimulation by 10 micron-noradrenaline and by 1.0nM-cyclic AMP of the phospholipase A2-acylation system of isolated synaptic membranes."}
{"id": "PMID:195583", "title": "Feedback regulation of vitamin D metabolism by 1,25-dihydroxycholecalciferol.", "content": "Many factors influence the production of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol) by the kidney. One important factor seems to be feedback regulation by 1,25(OH)2D3 itself. Administration of 1,25(OH)2D3 to vitamin D-deficient chicks abolishes renal 25(OH)D3(25-hydroxycholecalciferol)1-hydroxylase activity and induces the appearance of 25(OH)D3 24-hydroxylase activity. It is likely that these effects are mediated via a nuclear effect, as they are prevented by pretreatment with actinomycin D and alpha-amanitin. Further, 1,25(OH)2D3 has a marked effect on gene transcription in the kidney cell, as assessed by measurement of RNA polymerase activities. RNA polymerase I and II activities are 80-90% inhibited by 12.5nmol of 1,25(OH)2D3 within 30min of subcutaneous administration, indicating an immediate and massive decrease in total gene transcription. By 4h RNA polymerase II activity has returned to control values, but RNA polymerase I activity is markedly enhanced. These results are consistent with the view that regulation of cholecalciferol metabolism in the kidney is associated with an effect of the active metabolite on the kidney nucleus.", "contents": "Feedback regulation of vitamin D metabolism by 1,25-dihydroxycholecalciferol. Many factors influence the production of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol) by the kidney. One important factor seems to be feedback regulation by 1,25(OH)2D3 itself. Administration of 1,25(OH)2D3 to vitamin D-deficient chicks abolishes renal 25(OH)D3(25-hydroxycholecalciferol)1-hydroxylase activity and induces the appearance of 25(OH)D3 24-hydroxylase activity. It is likely that these effects are mediated via a nuclear effect, as they are prevented by pretreatment with actinomycin D and alpha-amanitin. Further, 1,25(OH)2D3 has a marked effect on gene transcription in the kidney cell, as assessed by measurement of RNA polymerase activities. RNA polymerase I and II activities are 80-90% inhibited by 12.5nmol of 1,25(OH)2D3 within 30min of subcutaneous administration, indicating an immediate and massive decrease in total gene transcription. By 4h RNA polymerase II activity has returned to control values, but RNA polymerase I activity is markedly enhanced. These results are consistent with the view that regulation of cholecalciferol metabolism in the kidney is associated with an effect of the active metabolite on the kidney nucleus."}
{"id": "PMID:195584", "title": "The nature of controlled respiration and its relationship to protonmotive force and proton conductance in blowfly flight-muscle mitochondria.", "content": "1. To determine whether controlled (State 4) pyruvate oxidation can support a high energy state, measurements of the redox span NAD-cytochrome c, phosphorylation potential and protonmotive force (the gradient in electrochemical activity of protons across the mitochondrial inner membrane) were made as indices of energy status. For comparison, these three measurements were also made with glycerol 3-phosphate, an alternative substrate. The two substrates gave essentially identical values for the redox span NAD-cytochrome c in State 4, and the phosphorylation potential was of sufficient magnitude to be considered in equilibrium with the redox span over the first two phosphorylation sites. The magnitude of the protonmotive force in State 4 was much less and the implications of this finding are discussed. 2. Measurements made during the controlled (State 4) to active (State 3) transition indicated that with glycerol 3-phosphate as substrate, both the redox span NAD-cytochrome c and the protonmotive force were diminished; the State 4 --> State 3 transition with pyruvate as substrate was accompanied by an increase in the redox span but a decrease in protonmotive force. The contrary behaviour of these two energetic parameters in the presence of pyruvate was ascribed to a transient excess in the flux of protons through the adenosine triphosphatase relative to the protonpumping respiratory chain, in spite of the increased dehydrogenase activity. 3. The lower protonmotive force seen in State 3 relative to State 4 with pyruvate as substrate was due to a diminution of both the electrical (DeltaPsi) and the chemical (DeltapH) components; with glycerol 3-phosphate, the magnitude of the decrease in protonmotive force during the State 4 --> State 3 transition was similar to that seen with pyruvate, but was due to a large decrease in the electrical component (DeltaPsi) and a small rise in the chemical component (DeltapH). The reason for the difference seen in the behaviour of the components of the protonmotive force was investigated but not established. 4. In the presence of oligomycin and ADP, oxidation of pyruvate, but not of glycerol 3-phosphate, supported a greater protonmotive force than in State 4, in keeping with the dehydrogenase activation and increased redox span NAD-cytochrome c found under these conditions. 5. Experiments involving the use of uncoupling agent to stimulate respiration are compared with those in which limiting concentrations of ADP were used. Estimates of the proton conductance of the inner membrane indicate a similar non-linear dependence on uncoupler concentration with the two substrates. 6. A model is proposed as an explanation of the high rates of controlled glycerol 3-phosphate oxidation. The model relies on a high permeability of the inner membrane to protons and other ions being induced by glycerol 3-phosphate oxidation in State 4.", "contents": "The nature of controlled respiration and its relationship to protonmotive force and proton conductance in blowfly flight-muscle mitochondria. 1. To determine whether controlled (State 4) pyruvate oxidation can support a high energy state, measurements of the redox span NAD-cytochrome c, phosphorylation potential and protonmotive force (the gradient in electrochemical activity of protons across the mitochondrial inner membrane) were made as indices of energy status. For comparison, these three measurements were also made with glycerol 3-phosphate, an alternative substrate. The two substrates gave essentially identical values for the redox span NAD-cytochrome c in State 4, and the phosphorylation potential was of sufficient magnitude to be considered in equilibrium with the redox span over the first two phosphorylation sites. The magnitude of the protonmotive force in State 4 was much less and the implications of this finding are discussed. 2. Measurements made during the controlled (State 4) to active (State 3) transition indicated that with glycerol 3-phosphate as substrate, both the redox span NAD-cytochrome c and the protonmotive force were diminished; the State 4 --> State 3 transition with pyruvate as substrate was accompanied by an increase in the redox span but a decrease in protonmotive force. The contrary behaviour of these two energetic parameters in the presence of pyruvate was ascribed to a transient excess in the flux of protons through the adenosine triphosphatase relative to the protonpumping respiratory chain, in spite of the increased dehydrogenase activity. 3. The lower protonmotive force seen in State 3 relative to State 4 with pyruvate as substrate was due to a diminution of both the electrical (DeltaPsi) and the chemical (DeltapH) components; with glycerol 3-phosphate, the magnitude of the decrease in protonmotive force during the State 4 --> State 3 transition was similar to that seen with pyruvate, but was due to a large decrease in the electrical component (DeltaPsi) and a small rise in the chemical component (DeltapH). The reason for the difference seen in the behaviour of the components of the protonmotive force was investigated but not established. 4. In the presence of oligomycin and ADP, oxidation of pyruvate, but not of glycerol 3-phosphate, supported a greater protonmotive force than in State 4, in keeping with the dehydrogenase activation and increased redox span NAD-cytochrome c found under these conditions. 5. Experiments involving the use of uncoupling agent to stimulate respiration are compared with those in which limiting concentrations of ADP were used. Estimates of the proton conductance of the inner membrane indicate a similar non-linear dependence on uncoupler concentration with the two substrates. 6. A model is proposed as an explanation of the high rates of controlled glycerol 3-phosphate oxidation. The model relies on a high permeability of the inner membrane to protons and other ions being induced by glycerol 3-phosphate oxidation in State 4."}
{"id": "PMID:195585", "title": "Uridine kinase activities and pyrimidine nucleoside phosphorylation in fluoropyrimidine-sensitive and -resistant cell lines of the Novikoff hepatoma.", "content": "Uridine kinase, the rate-limiting enzyme in the activation (phosphorylation) of uridine and the corresponding chemotherapeutic analogues, is present as two isoenzymes localized exclusively in the cytosol of rapidly growing neoplasms, including the S-37 sarcoma, EL-4 leukaemia, HeLa cells (a human carcinoma) and the Novikoff hepatoma. The activities of the isolated isoenzymes are markedly decreased when the concentrations of ATP, phosphate or Mg2+ that are optimum in vitro are replaced by concentrations of ATP, phosphate or Mg2+ that are optimum in vitro are replaced by concentrations approximating to those found in vivo. Further, comparisons of the Km values of isolated uridine kinases with those for cellular uptake of pyrimidine nucleosides and their rate of intracellular phosphorylation suggest that nucleoside-transport systems play a rate-limiting role in nucleoside analogue activation and consequently that it is impossible to estimate the Km of uridine kinase in the intact cell. During the development of tumour-cell resistance to 5-fluorouracil or 5-fluorouridine in vivo there was an early differential increase in the activity of a low-affinity (high-Km) uridine kinase isoenzyme, as measured in cell extracts, and a 7-fold increase in the Km values for the uptake of both uridine and 5-fluorouridine into the intact resistant cells.", "contents": "Uridine kinase activities and pyrimidine nucleoside phosphorylation in fluoropyrimidine-sensitive and -resistant cell lines of the Novikoff hepatoma. Uridine kinase, the rate-limiting enzyme in the activation (phosphorylation) of uridine and the corresponding chemotherapeutic analogues, is present as two isoenzymes localized exclusively in the cytosol of rapidly growing neoplasms, including the S-37 sarcoma, EL-4 leukaemia, HeLa cells (a human carcinoma) and the Novikoff hepatoma. The activities of the isolated isoenzymes are markedly decreased when the concentrations of ATP, phosphate or Mg2+ that are optimum in vitro are replaced by concentrations of ATP, phosphate or Mg2+ that are optimum in vitro are replaced by concentrations approximating to those found in vivo. Further, comparisons of the Km values of isolated uridine kinases with those for cellular uptake of pyrimidine nucleosides and their rate of intracellular phosphorylation suggest that nucleoside-transport systems play a rate-limiting role in nucleoside analogue activation and consequently that it is impossible to estimate the Km of uridine kinase in the intact cell. During the development of tumour-cell resistance to 5-fluorouracil or 5-fluorouridine in vivo there was an early differential increase in the activity of a low-affinity (high-Km) uridine kinase isoenzyme, as measured in cell extracts, and a 7-fold increase in the Km values for the uptake of both uridine and 5-fluorouridine into the intact resistant cells."}
{"id": "PMID:195586", "title": "Inhibition of binding of corticotropin-(1-24)-tetracosapeptide (Synacthen) to membrane receptors of adrenal cortex by cortisol.", "content": "The binding of Synacthen to partially purified bovine adrenocortical plasma membranes was shown to be inhibited by cortisol. The findings suggest that cortisol is involved in a peripheral feedback mechanism for the control of its release.", "contents": "Inhibition of binding of corticotropin-(1-24)-tetracosapeptide (Synacthen) to membrane receptors of adrenal cortex by cortisol. The binding of Synacthen to partially purified bovine adrenocortical plasma membranes was shown to be inhibited by cortisol. The findings suggest that cortisol is involved in a peripheral feedback mechanism for the control of its release."}
{"id": "PMID:195590", "title": "1,4-Bis-[1-methyl-5-nitroimidazolyl-(2-methyleneimino)]-piperazine, a new drug with marked activity against Entamoeba histolytica. Short communication.", "content": "1,4-Bis-[1-methyl-5-nitroimidazolyl-(2-methyleneimino)]-piperazine (HOE 316) administered orally produces an effect which is clearly superior to that of metronidazole against Entamoeba histolytica in the golden hamster and slightly inferior against Trichomonas fetus and T. vaginalis in the mouse. The acute tolerance of the compound is very good (LD 50% greater than 10 g/kg body weight). It is assumed that the possible main metabolite of HOE 316 is a monohydrazone: 1-methyl-2-(4-amino-piperazino-1-imino-methyl)-5-nitroimidazole.", "contents": "1,4-Bis-[1-methyl-5-nitroimidazolyl-(2-methyleneimino)]-piperazine, a new drug with marked activity against Entamoeba histolytica. Short communication. 1,4-Bis-[1-methyl-5-nitroimidazolyl-(2-methyleneimino)]-piperazine (HOE 316) administered orally produces an effect which is clearly superior to that of metronidazole against Entamoeba histolytica in the golden hamster and slightly inferior against Trichomonas fetus and T. vaginalis in the mouse. The acute tolerance of the compound is very good (LD 50% greater than 10 g/kg body weight). It is assumed that the possible main metabolite of HOE 316 is a monohydrazone: 1-methyl-2-(4-amino-piperazino-1-imino-methyl)-5-nitroimidazole."}
{"id": "PMID:195594", "title": "Purification and characterization of high-molecular-weight forms of adrenocorticotropic hormone of ovine pituitary glands.", "content": "A highly purified preparation of high-molecular-weight adrenocorticotropic hormone (ACTH) was prepared from ovine pituitary glands by dilute acetic acid extraction, oxycellulose fractionation. Sephadex gel filtration, and affinity chromatography on immobilized alphap(1-39)ACTH antibodies. Two ACTH peptides of molecular weights of 24 000 and 34 000 were detected by sodium dodecyl sulfate-acrylamide gel electrophoresis in this preparation. It appeared that the immobilized antibodies adsorbed two forms equally well and could not distinguish between them under the conditions used. These two ACTH peptides were found to be present in crude extracts of ovine pituitary glands, indicating that they were not artifacts produced by the purification procedure. The high-molecular-weight forms of ACTH were found to be susceptible to degradation by tissue enzymes. They could be easily destroyed during the extraction, if precautions were not taken. Moreover, they were poorly adsorbed by oxycellulose which had been used for the adsorption of ACTH activity from crude preparations by most investigators. These properties probably accounted for the fact that high-molecular-weight forms of ACTH remained undetected until very recently.", "contents": "Purification and characterization of high-molecular-weight forms of adrenocorticotropic hormone of ovine pituitary glands. A highly purified preparation of high-molecular-weight adrenocorticotropic hormone (ACTH) was prepared from ovine pituitary glands by dilute acetic acid extraction, oxycellulose fractionation. Sephadex gel filtration, and affinity chromatography on immobilized alphap(1-39)ACTH antibodies. Two ACTH peptides of molecular weights of 24 000 and 34 000 were detected by sodium dodecyl sulfate-acrylamide gel electrophoresis in this preparation. It appeared that the immobilized antibodies adsorbed two forms equally well and could not distinguish between them under the conditions used. These two ACTH peptides were found to be present in crude extracts of ovine pituitary glands, indicating that they were not artifacts produced by the purification procedure. The high-molecular-weight forms of ACTH were found to be susceptible to degradation by tissue enzymes. They could be easily destroyed during the extraction, if precautions were not taken. Moreover, they were poorly adsorbed by oxycellulose which had been used for the adsorption of ACTH activity from crude preparations by most investigators. These properties probably accounted for the fact that high-molecular-weight forms of ACTH remained undetected until very recently."}
{"id": "PMID:195596", "title": "A comparison of membrane components of normal and transformed BALB/c cells.", "content": "Membrane glycolipids, glycoproteins, and surface proteins of normal and transformed BALB/c cell lines have been compared. Several virally and spontaneously transformed cell lines showed differences in membrane components compared to normal A31 cells. These differences consisted of increased amounts of simpler gangliosides, absence of the large external transformation sensitive (LETS) protein, and the appearance of a major new glycoprotein band of about 105 000 molecular weight. In contrast, the spontaneously transformed cell line that caused the fastest growing tumors in vivo and the most rapid animal death (3T12T) did not have these changes. A31 and 3T12T glycolipid profiles appear similar as did glycoproteins and cell surface proteins detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When Pronase-generated glycopeptides were analyzed by Sephadex G-50 chromatography, and enrichment in faster-eluting species was seen in two killing tumor lines (c5T and 3T12T) compared to A31. Regressing tumor lines (MSC, c5) did not show this change. Isolated membrane glycoproteins yield glycopeptides of different sized after Pronase digestion. In addition, several 3T12T glycoproteins yield glycopeptides that are larger than those from the corresponding glycoproteins of A31 cells. It appears that glycopeptide alterations associated with transformation occur in several membrane glycoproteins.", "contents": "A comparison of membrane components of normal and transformed BALB/c cells. Membrane glycolipids, glycoproteins, and surface proteins of normal and transformed BALB/c cell lines have been compared. Several virally and spontaneously transformed cell lines showed differences in membrane components compared to normal A31 cells. These differences consisted of increased amounts of simpler gangliosides, absence of the large external transformation sensitive (LETS) protein, and the appearance of a major new glycoprotein band of about 105 000 molecular weight. In contrast, the spontaneously transformed cell line that caused the fastest growing tumors in vivo and the most rapid animal death (3T12T) did not have these changes. A31 and 3T12T glycolipid profiles appear similar as did glycoproteins and cell surface proteins detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When Pronase-generated glycopeptides were analyzed by Sephadex G-50 chromatography, and enrichment in faster-eluting species was seen in two killing tumor lines (c5T and 3T12T) compared to A31. Regressing tumor lines (MSC, c5) did not show this change. Isolated membrane glycoproteins yield glycopeptides of different sized after Pronase digestion. In addition, several 3T12T glycoproteins yield glycopeptides that are larger than those from the corresponding glycoproteins of A31 cells. It appears that glycopeptide alterations associated with transformation occur in several membrane glycoproteins."}
{"id": "PMID:195597", "title": "Characterization of collagen precursors found in rat skin and rat bone.", "content": "Two genetic types of collagenous proteins, type I and type III, were isolated by extraction and differential salt precipitation from rat skin. The yield of collagen precursors was increased by injecting animals with colchicine 30 min before sacrifice to inhibit secretion of collagen. DEAE-cellulose chromatography was used to separate collagen from collagen precursors. Although these preparations contained more type I collagen than type III collagen, there were always more type III than type I precursors. The precursor chains of type I fractions were separated on CM-cellulose chromatography after denaturation. Three precursor forms were found for each collagen alpha chain, a complete chain (proalpha chain), and a precursor chain with only an amino-terminal (pNalpha chain) and carboxy-terminal extension (pCalpha chain). Species differences were demonstrated between rat collagen precursors and other species using rat calvaria (frontal and parietal) bones extracted with either 0.5 N acetic acid or neutral salt buffers containing protease inhibitors. Native rat procollagen elutes earlier than chicken or human procollagen on DEAE-cellulose chromatography and does not separate significantly from the pC collagen form. The collagenase resistant amino terminal peptides of rat pNalpha1 and pNalpha2 were the same size (16 000) but could be separated by DEAE-cellulose chromatography.", "contents": "Characterization of collagen precursors found in rat skin and rat bone. Two genetic types of collagenous proteins, type I and type III, were isolated by extraction and differential salt precipitation from rat skin. The yield of collagen precursors was increased by injecting animals with colchicine 30 min before sacrifice to inhibit secretion of collagen. DEAE-cellulose chromatography was used to separate collagen from collagen precursors. Although these preparations contained more type I collagen than type III collagen, there were always more type III than type I precursors. The precursor chains of type I fractions were separated on CM-cellulose chromatography after denaturation. Three precursor forms were found for each collagen alpha chain, a complete chain (proalpha chain), and a precursor chain with only an amino-terminal (pNalpha chain) and carboxy-terminal extension (pCalpha chain). Species differences were demonstrated between rat collagen precursors and other species using rat calvaria (frontal and parietal) bones extracted with either 0.5 N acetic acid or neutral salt buffers containing protease inhibitors. Native rat procollagen elutes earlier than chicken or human procollagen on DEAE-cellulose chromatography and does not separate significantly from the pC collagen form. The collagenase resistant amino terminal peptides of rat pNalpha1 and pNalpha2 were the same size (16 000) but could be separated by DEAE-cellulose chromatography."}
{"id": "PMID:195599", "title": "Kinetic studies on redox reactions of hemoproteins. I. Reduction of thermoresistant cytochrome c-552 and horse heart cytochrome c by ferrocyanide.", "content": "The oxidation-reduction reaction of horse heart cytochrome c and cytochrome c (552, Thermus thermophilus), which is highly thermoresistant, was studied by temperature-jump method. Ferrohexacyanide was used as reductant. (Formula: see text.) Thermodynamic and activation parameters of the reaction obtained for both cytochromes were compared with each other. The results of this showed that (1) the redox potential of cytochrome c-552, + 0.19 V, is markedly less than that of horse heart cytochrome c. (2) deltaHox of cytochrome c-552 is considerably lower than that of horse heart cytochrome c. (3) deltaSox and deltaSred of cytochrome c-552 are more negative than those of horse heart cytochrome c. (4) kred of cytochrome c-552 is much lower than that of horse heart cytochrome c at room temperature.", "contents": "Kinetic studies on redox reactions of hemoproteins. I. Reduction of thermoresistant cytochrome c-552 and horse heart cytochrome c by ferrocyanide. The oxidation-reduction reaction of horse heart cytochrome c and cytochrome c (552, Thermus thermophilus), which is highly thermoresistant, was studied by temperature-jump method. Ferrohexacyanide was used as reductant. (Formula: see text.) Thermodynamic and activation parameters of the reaction obtained for both cytochromes were compared with each other. The results of this showed that (1) the redox potential of cytochrome c-552, + 0.19 V, is markedly less than that of horse heart cytochrome c. (2) deltaHox of cytochrome c-552 is considerably lower than that of horse heart cytochrome c. (3) deltaSox and deltaSred of cytochrome c-552 are more negative than those of horse heart cytochrome c. (4) kred of cytochrome c-552 is much lower than that of horse heart cytochrome c at room temperature."}
{"id": "PMID:195600", "title": "Uptake of ATP analogs by isolated pea chloroplasts and their effect on CO2 fixation and electron transport.", "content": "1. The ATP analog, adenylyl-imidodiphosphate rapidly inhibited CO2-dependent oxygen evolution by isolated pea chloroplasts. Both alpha, beta- and beta, gamma-methylene adenosine triphosphate also inhibited oxygen evolution. The inhibition was relieved by ATP but only partially relieved by 3-phosphoglycerate. Oxygen evolution with 3-phosphoglycerate as substrate was inhibited by adenylyl-imidodiphosphate to a lesser extent than CO2-dependent oxygen evolution. The concentration of adenylylimidodiphosphate required for 50% inhibition of CO2-dependent oxygen evolution was 50 micronM. 2. Although non-cyclic photophosphorylation by broken chloroplasts was not significantly affected by adenylyl-imidodiphosphate, electron transport in the absence of ADP was inhibited by adenylyl-imidodiphosphate to the same extent as by ATP, suggesting binding of the ATP analog to the coupling factor of phosphorylation. 3. The endogenous adenine nucleotides of a chloroplast suspension were labelled by incubation with [14C]ATP and subsequent washing. Addition of adenylyl-imidodiphosphate to the labelled chloroplasts resulted in a rapid efflux of adenine nucleotides suggesting that the ATP analog was transported into the chloroplasts via the adenine nucleotide translocator. 4. It was concluded that uptake of ATP analogs in exchange for endogenous adenine nucleotides decreased the internal ATP concentration and thus inhibited CO2 fixation. Oxygen evolution was inhibited to a lesser extent in spinach chloroplasts which apparently have lower rates of adenine nucleotide transport than pea chloroplasts.", "contents": "Uptake of ATP analogs by isolated pea chloroplasts and their effect on CO2 fixation and electron transport. 1. The ATP analog, adenylyl-imidodiphosphate rapidly inhibited CO2-dependent oxygen evolution by isolated pea chloroplasts. Both alpha, beta- and beta, gamma-methylene adenosine triphosphate also inhibited oxygen evolution. The inhibition was relieved by ATP but only partially relieved by 3-phosphoglycerate. Oxygen evolution with 3-phosphoglycerate as substrate was inhibited by adenylyl-imidodiphosphate to a lesser extent than CO2-dependent oxygen evolution. The concentration of adenylylimidodiphosphate required for 50% inhibition of CO2-dependent oxygen evolution was 50 micronM. 2. Although non-cyclic photophosphorylation by broken chloroplasts was not significantly affected by adenylyl-imidodiphosphate, electron transport in the absence of ADP was inhibited by adenylyl-imidodiphosphate to the same extent as by ATP, suggesting binding of the ATP analog to the coupling factor of phosphorylation. 3. The endogenous adenine nucleotides of a chloroplast suspension were labelled by incubation with [14C]ATP and subsequent washing. Addition of adenylyl-imidodiphosphate to the labelled chloroplasts resulted in a rapid efflux of adenine nucleotides suggesting that the ATP analog was transported into the chloroplasts via the adenine nucleotide translocator. 4. It was concluded that uptake of ATP analogs in exchange for endogenous adenine nucleotides decreased the internal ATP concentration and thus inhibited CO2 fixation. Oxygen evolution was inhibited to a lesser extent in spinach chloroplasts which apparently have lower rates of adenine nucleotide transport than pea chloroplasts."}
{"id": "PMID:195601", "title": "Aerobic respiration in mutants of Escherichia coli accumulating quinone analogues of ubiquinone.", "content": "The ability of three naturally occurring analogues of ubiquinone to function in aerobic respiration in Escherichia coli has been studied. The compounds, which differ from ubiquinone in terms of the substituents on the quinone ring, accumulate in the cytoplasmic membranes of ubiE-, ubiF- and ubiG- mutants. One of the analogues (2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone, NMQ), which lacks the 5-methoxyl group of the benzoquinone ring of ubiquinone promoted the oxidation of NADH, D-lactate and alpha-glycerophosphate but not succinate. Electron transport supported by MMQ was found to be coupled to phosphorylation. In contrast, 2-octaprenyl-6-methoxy-1,4-benzoquinone, which lacks both the 3-methyl and 5-methoxyl groups of ubiquinone, and 2-octaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4-benzoquinone, in which the 5-methoxyl group of ubiquinone is replaced by an hydroxyl group, were virtually inactive in the oxidases tested. The ability of MMQ to function in respiration in isolated membranes is consistent with the findings that the growth rate and yield of a ubiF- strain, unlike other ubi- strains, were only slightly lower than those of a ubiF+ strain. The fact that MMQ is active in some but not all oxidases provides further support for the concept that the quinones link the individual dehydrogenases to the respiratory chain and that each dehydrogenase has specific structural requirements for quinone acceptors.", "contents": "Aerobic respiration in mutants of Escherichia coli accumulating quinone analogues of ubiquinone. The ability of three naturally occurring analogues of ubiquinone to function in aerobic respiration in Escherichia coli has been studied. The compounds, which differ from ubiquinone in terms of the substituents on the quinone ring, accumulate in the cytoplasmic membranes of ubiE-, ubiF- and ubiG- mutants. One of the analogues (2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone, NMQ), which lacks the 5-methoxyl group of the benzoquinone ring of ubiquinone promoted the oxidation of NADH, D-lactate and alpha-glycerophosphate but not succinate. Electron transport supported by MMQ was found to be coupled to phosphorylation. In contrast, 2-octaprenyl-6-methoxy-1,4-benzoquinone, which lacks both the 3-methyl and 5-methoxyl groups of ubiquinone, and 2-octaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4-benzoquinone, in which the 5-methoxyl group of ubiquinone is replaced by an hydroxyl group, were virtually inactive in the oxidases tested. The ability of MMQ to function in respiration in isolated membranes is consistent with the findings that the growth rate and yield of a ubiF- strain, unlike other ubi- strains, were only slightly lower than those of a ubiF+ strain. The fact that MMQ is active in some but not all oxidases provides further support for the concept that the quinones link the individual dehydrogenases to the respiratory chain and that each dehydrogenase has specific structural requirements for quinone acceptors."}
{"id": "PMID:195602", "title": "Role of quinones in electron transport to oxygen and nitrate in Escherichia coli. Studies with a ubiA- menA- double quinone mutant.", "content": "A ubiA- menA- double quinone mutant of Escherichia coli K12 was constructed together with other isogenic strains lacking either ubiquinone or menaquinone. These strains were used to study the role of quinones in electron transport to oxygen and nitrate. Each of the four oxidases examined (NADH, D-lactate, alpha-glycerophosphate and succinate) required a quinone for activity. Ubiquinone was active in each oxidase system while menaquinone gave full activity in alpha-glycerophosphate oxidase, partial activity in D-lactate oxidase but was inactive in NADH and succinate oxidation. The aerobic growth rates, growth yields and products of glucose metabolism of the quinone-deficient strains were also examined. The growth rate and growth yield of the ubi+menA- strain was the same as the wild-type strain, whereas the ubiA-men+ strain grew more slowly on glucose, had a lower growth yield (30% of wild type) and accumulated relatively large quantities of acetate and lactate. The growth of the ubiA-menA- strain was even more severely affected than that of the ubiA-men+ strain. Electron transport from formate, D-lactate, alpha-glycerophosphate and NADH to nitrate was also highly dependent on the presence of a quinone. Either ubiquinone or menaquinone was active in electron transport from formate and the activity of the quinones in electron transport from the other substrates was the same as for the oxidase systems. In contrast, quinones were not obligatory carriers in the anaerobic formate hydrogenlyase system. It is concluded that the quinones serve to link the various dehydrogenases with the terminal electron transport systems to oxygen and nitrate and that the dehydrogenases possess a degree of selectivity with respect to the quinone acceptors.", "contents": "Role of quinones in electron transport to oxygen and nitrate in Escherichia coli. Studies with a ubiA- menA- double quinone mutant. A ubiA- menA- double quinone mutant of Escherichia coli K12 was constructed together with other isogenic strains lacking either ubiquinone or menaquinone. These strains were used to study the role of quinones in electron transport to oxygen and nitrate. Each of the four oxidases examined (NADH, D-lactate, alpha-glycerophosphate and succinate) required a quinone for activity. Ubiquinone was active in each oxidase system while menaquinone gave full activity in alpha-glycerophosphate oxidase, partial activity in D-lactate oxidase but was inactive in NADH and succinate oxidation. The aerobic growth rates, growth yields and products of glucose metabolism of the quinone-deficient strains were also examined. The growth rate and growth yield of the ubi+menA- strain was the same as the wild-type strain, whereas the ubiA-men+ strain grew more slowly on glucose, had a lower growth yield (30% of wild type) and accumulated relatively large quantities of acetate and lactate. The growth of the ubiA-menA- strain was even more severely affected than that of the ubiA-men+ strain. Electron transport from formate, D-lactate, alpha-glycerophosphate and NADH to nitrate was also highly dependent on the presence of a quinone. Either ubiquinone or menaquinone was active in electron transport from formate and the activity of the quinones in electron transport from the other substrates was the same as for the oxidase systems. In contrast, quinones were not obligatory carriers in the anaerobic formate hydrogenlyase system. It is concluded that the quinones serve to link the various dehydrogenases with the terminal electron transport systems to oxygen and nitrate and that the dehydrogenases possess a degree of selectivity with respect to the quinone acceptors."}
{"id": "PMID:195605", "title": "Modulation of drug permeability in Chinese hamster ovary cells. Possible role for phosphorylation of surface glycoproteins.", "content": "We have previously reported that the uptake of colchicine and other drugs in Chinese hamster ovary (CHO) cells can be greatly enhanced by the addition of metabolic inhibitors such as cyanide (See, Y.P., Carlsen, S.A., Till, J.E. and Ling, V. (1974) Biochim. Biophys. Acta 373, 242-252). This has led us to postulate the presence of an active drug permeability barrier in these cells. In this paper we provide evidence for the dependence of this permeability barrier on intracellular ATP levels. Colchicine-resistant mutants of CHO cells exhibiting a reduced drug permeability, however, can maintain this drug permeability barrier at much lower ATP levels, suggesting that they possess an altered active drug permeability barrier. We have also observed a membrane-associated protein kinase-phosphoprotein phosphatase system in the isolated membranes of mutant and wild-type cells. Differences in the intrinsic protein phosphorylation patterns between the membranes of these cells have led us to conclude that the control of the drug permeability barrier may be mediated via the phosphorylation of at least two high molecular weight surface glycoproteins.", "contents": "Modulation of drug permeability in Chinese hamster ovary cells. Possible role for phosphorylation of surface glycoproteins. We have previously reported that the uptake of colchicine and other drugs in Chinese hamster ovary (CHO) cells can be greatly enhanced by the addition of metabolic inhibitors such as cyanide (See, Y.P., Carlsen, S.A., Till, J.E. and Ling, V. (1974) Biochim. Biophys. Acta 373, 242-252). This has led us to postulate the presence of an active drug permeability barrier in these cells. In this paper we provide evidence for the dependence of this permeability barrier on intracellular ATP levels. Colchicine-resistant mutants of CHO cells exhibiting a reduced drug permeability, however, can maintain this drug permeability barrier at much lower ATP levels, suggesting that they possess an altered active drug permeability barrier. We have also observed a membrane-associated protein kinase-phosphoprotein phosphatase system in the isolated membranes of mutant and wild-type cells. Differences in the intrinsic protein phosphorylation patterns between the membranes of these cells have led us to conclude that the control of the drug permeability barrier may be mediated via the phosphorylation of at least two high molecular weight surface glycoproteins."}
{"id": "PMID:195607", "title": "Cyclic AMP modulation of calcium accumulation by sarcoplasmic reticulum from fast skeletal muscle.", "content": "The role of cyclic 3',5'-AMP in modulating sarcoplasmic reticulum from fast skeletal muscle was studied. The rate of Ca2+ uptake was stimulated in the presence of protein kinase plus 1 micron cyclic AMP. The stimulation was absent when denatured protein kinase was used. When an adenylate cyclase inhibitor was added, the uptake rates fell to 55% of control. This decrease in rate was partially overcome by 1 micron cyclic AMP. A modulating role for cyclic AMP in fast skeletal muscle is proposed.", "contents": "Cyclic AMP modulation of calcium accumulation by sarcoplasmic reticulum from fast skeletal muscle. The role of cyclic 3',5'-AMP in modulating sarcoplasmic reticulum from fast skeletal muscle was studied. The rate of Ca2+ uptake was stimulated in the presence of protein kinase plus 1 micron cyclic AMP. The stimulation was absent when denatured protein kinase was used. When an adenylate cyclase inhibitor was added, the uptake rates fell to 55% of control. This decrease in rate was partially overcome by 1 micron cyclic AMP. A modulating role for cyclic AMP in fast skeletal muscle is proposed."}
{"id": "PMID:195610", "title": "Decreased iodination of the red cell surface following phospholipase C treatment.", "content": "Human red blood cells were treated with phospholipase C from Clostridium welchii. Lipase concentrations which produced less than 1% hemolysis and 10-15% hydrolysis of the membrane phospholipids reduced markedly (greater than 80%) the accessibility of membrane proteins to the external surface as measured by lactoperoxidase-catalyzed iodination.", "contents": "Decreased iodination of the red cell surface following phospholipase C treatment. Human red blood cells were treated with phospholipase C from Clostridium welchii. Lipase concentrations which produced less than 1% hemolysis and 10-15% hydrolysis of the membrane phospholipids reduced markedly (greater than 80%) the accessibility of membrane proteins to the external surface as measured by lactoperoxidase-catalyzed iodination."}
{"id": "PMID:195611", "title": "Genetic regulation of the constitutive D-ribose operon in Escherichia coli B/r.", "content": "Merodiploid complementation analysis of the constitutive synthesis of the D-ribokinase and the D-ribose permease in Escherichia coli B/r has shown that the constitutive D-ribose operon is genetically controlled by a transdominant regulatory gene closely linked to the D-ribokinase and D-ribose permease structural genes. The regulatory mechanism for this operon shows no requirement for operator-repressor interaction, rather a truly positive control mechanism and thus suggests an extension of the operon model in its application to constitutive enzyme regulation in bacteria.", "contents": "Genetic regulation of the constitutive D-ribose operon in Escherichia coli B/r. Merodiploid complementation analysis of the constitutive synthesis of the D-ribokinase and the D-ribose permease in Escherichia coli B/r has shown that the constitutive D-ribose operon is genetically controlled by a transdominant regulatory gene closely linked to the D-ribokinase and D-ribose permease structural genes. The regulatory mechanism for this operon shows no requirement for operator-repressor interaction, rather a truly positive control mechanism and thus suggests an extension of the operon model in its application to constitutive enzyme regulation in bacteria."}
{"id": "PMID:195612", "title": "Involvement of NAD  in induced synthesis of colicin E1.", "content": "Escherichia coli K-12 nadC13 (ColE1) was starved for nicotinic acid and cellular NAD levels decreased to less than 10% of the normal. Under these conditions, induction of colicin E1 synthesis decreased to about 1% of the normal value, while 30% of the total protein synthesis remained intact. Addition of nicotinic acid reversed both the ability of the colicin induction and cellular NAD level. Induced replication of colicin E1 DNA was greatly reduced in the NAD-deprived cells.", "contents": "Involvement of NAD  in induced synthesis of colicin E1. Escherichia coli K-12 nadC13 (ColE1) was starved for nicotinic acid and cellular NAD levels decreased to less than 10% of the normal. Under these conditions, induction of colicin E1 synthesis decreased to about 1% of the normal value, while 30% of the total protein synthesis remained intact. Addition of nicotinic acid reversed both the ability of the colicin induction and cellular NAD level. Induced replication of colicin E1 DNA was greatly reduced in the NAD-deprived cells."}
{"id": "PMID:195613", "title": "Stimulation of synthesis of the proteins of 30-S nuclear ribonucleoprotein particles in human amnion U cells by viral infection.", "content": "Early increase in RNA synthesis induced in human amnion U cells by infection with poliovirus is accompanied by an increased incorporation of amino acids into non-histone nuclear proteins with an approximate molecular weight of 40 000. These proteins are the main polypeptides of the 30-S nuclear ribonucleoprotein particles. After fractionation of nuclear proteins by extraction with solutions of different ionic strength, these polypeptides are present in the fraction of nuclear sap proteins soluble in 0.1 M Tris - HCl buffer, pH 7.6, and in the fraction of non-histone chromosomal proteins which are soluble in 0.35 M NaCl. The increase in synthesis of non-histone nuclear proteins with an approximate molecular weight of 40 000, observed in the infected cells, represents an increase in the synthesis of proteins concerned with post-transcriptional events and, therefore, is the result and not the cause of gene activation.", "contents": "Stimulation of synthesis of the proteins of 30-S nuclear ribonucleoprotein particles in human amnion U cells by viral infection. Early increase in RNA synthesis induced in human amnion U cells by infection with poliovirus is accompanied by an increased incorporation of amino acids into non-histone nuclear proteins with an approximate molecular weight of 40 000. These proteins are the main polypeptides of the 30-S nuclear ribonucleoprotein particles. After fractionation of nuclear proteins by extraction with solutions of different ionic strength, these polypeptides are present in the fraction of nuclear sap proteins soluble in 0.1 M Tris - HCl buffer, pH 7.6, and in the fraction of non-histone chromosomal proteins which are soluble in 0.35 M NaCl. The increase in synthesis of non-histone nuclear proteins with an approximate molecular weight of 40 000, observed in the infected cells, represents an increase in the synthesis of proteins concerned with post-transcriptional events and, therefore, is the result and not the cause of gene activation."}
{"id": "PMID:195614", "title": "Influence of dibutyryl cyclic AMP on thymidine uptake by herpes simplex virus infected cells and the intracellular level of cyclic AMP.", "content": "Dibutyryl cyclic AMP inhibits the increase of dThd and BrdUrd transport normally observed after infection with Herpesvirus hominis, type I and II. Incorporation is also reduced. Inhibition of uptake is non-competitive as analysed by the Lineweaver-Burk plot. Addition of this drug to infected cells also reduces the activity of the thymidine kinase (EC 2.7.1.75). Transport of dUrd, dCyd and dAdo is not reduced. 4--8 h after infection with thymidine kinase (+) herpes strains the level of cAMP increases. On infection with a thymidine kinase (-) virus, only a small elevation  of cAMP can be shown. It was also found that early addition of actinomycin D or of cycloheximide prevents the increase of the cAMP level. This increase seems to depend on the activity of the herpes genome, because ultraviolet irradiation of infective particles destroys this ability.", "contents": "Influence of dibutyryl cyclic AMP on thymidine uptake by herpes simplex virus infected cells and the intracellular level of cyclic AMP. Dibutyryl cyclic AMP inhibits the increase of dThd and BrdUrd transport normally observed after infection with Herpesvirus hominis, type I and II. Incorporation is also reduced. Inhibition of uptake is non-competitive as analysed by the Lineweaver-Burk plot. Addition of this drug to infected cells also reduces the activity of the thymidine kinase (EC 2.7.1.75). Transport of dUrd, dCyd and dAdo is not reduced. 4--8 h after infection with thymidine kinase (+) herpes strains the level of cAMP increases. On infection with a thymidine kinase (-) virus, only a small elevation  of cAMP can be shown. It was also found that early addition of actinomycin D or of cycloheximide prevents the increase of the cAMP level. This increase seems to depend on the activity of the herpes genome, because ultraviolet irradiation of infective particles destroys this ability."}
{"id": "PMID:195616", "title": "Mitochondrial biogenesis in cultured animal cells. I. Effect of chloramphenicol on morphology and mitochondrial respiratory enzymes.", "content": "The effects of chloramphenicol on the morphology and respiratory enzymes of BHK-21 cells in spinner culture have been examined with time. Cells treated with chloramphenicol double twice before growth ceases; these cells have increased size as measured by several techniques. Mitochondria are enlarged and appear to degenerate with prolonged treatment. Cytochrome c oxidase and succinate cytochrome c reductase activities are reduced while there is no decrease in the activities of monoamine oxidase, glutamate dehydrogenase or NADPH-cytochrome c reductase. Cytochromes aa3 and b disappear on treatment while cytochromes c + c1 appears to be unaffected. All these effects are reversible if chloramphenicol is removed within a limited period of time.", "contents": "Mitochondrial biogenesis in cultured animal cells. I. Effect of chloramphenicol on morphology and mitochondrial respiratory enzymes. The effects of chloramphenicol on the morphology and respiratory enzymes of BHK-21 cells in spinner culture have been examined with time. Cells treated with chloramphenicol double twice before growth ceases; these cells have increased size as measured by several techniques. Mitochondria are enlarged and appear to degenerate with prolonged treatment. Cytochrome c oxidase and succinate cytochrome c reductase activities are reduced while there is no decrease in the activities of monoamine oxidase, glutamate dehydrogenase or NADPH-cytochrome c reductase. Cytochromes aa3 and b disappear on treatment while cytochromes c + c1 appears to be unaffected. All these effects are reversible if chloramphenicol is removed within a limited period of time."}
{"id": "PMID:195618", "title": "The effect of cyclic GMP on phosphofructokinase from rat tissues.", "content": "In view of the recently proposed hypothesis of biologic regulation through opposing influences of cyclic AMP and cyclic GMP, and since cyclic AMP is a well-known allosteric activator of phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11), the effect of cyclic GMP on the activity of this enzyme from several rat tissues was investigated. It was found that cyclic GMP exerted an inhibitory effect on the activity of rat heart and skeletal muscle phosphofructokinase. This effect was most pronounced under conditions in which the enzyme was partially inhibited by ATP or by citrate. Cyclic GMP also antagonized the deinhibitory action of cyclic AMP and other allosteric activators, such as glucose 1,6-bisphosphate or AMP, on the ATP or citrate-inhibited heart or muscle phosphofructokinase. In contrast to the heart and skeletal muscle phosphofructokinase, the adipose-tissue enzyme was not affected by cyclic GMP to any significant degree. The antagonistic action of cyclic GMP to the activation of heart-phosphofructokinase, may suggest a mechanism by which the activity of phosphofructokinase is synchronized with the activity of glycogen phosphorylase, as a result of acetylcholine action in heart, to achieve a decrease in total glycogenolysis and glycolysis.", "contents": "The effect of cyclic GMP on phosphofructokinase from rat tissues. In view of the recently proposed hypothesis of biologic regulation through opposing influences of cyclic AMP and cyclic GMP, and since cyclic AMP is a well-known allosteric activator of phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11), the effect of cyclic GMP on the activity of this enzyme from several rat tissues was investigated. It was found that cyclic GMP exerted an inhibitory effect on the activity of rat heart and skeletal muscle phosphofructokinase. This effect was most pronounced under conditions in which the enzyme was partially inhibited by ATP or by citrate. Cyclic GMP also antagonized the deinhibitory action of cyclic AMP and other allosteric activators, such as glucose 1,6-bisphosphate or AMP, on the ATP or citrate-inhibited heart or muscle phosphofructokinase. In contrast to the heart and skeletal muscle phosphofructokinase, the adipose-tissue enzyme was not affected by cyclic GMP to any significant degree. The antagonistic action of cyclic GMP to the activation of heart-phosphofructokinase, may suggest a mechanism by which the activity of phosphofructokinase is synchronized with the activity of glycogen phosphorylase, as a result of acetylcholine action in heart, to achieve a decrease in total glycogenolysis and glycolysis."}
{"id": "PMID:195619", "title": "A continuous fluorometric assay for flavokinase. Properties of flavokinase from Peptostreptococcus elsdenii.", "content": "A continuous fluorometric assay that utilizes apoflavodoxin as a trapping agent for riboflavin 5'-phosphate (FMN) has been developed for flavokinase (ATP:riboflavin 5'-phosphotransferase, EC 2.7.1.26). Use of this assay is illustrated in a procedure for the partial purification of flavokinase from the strict anaerobe Peptostreptococcus elsdenii. The purified enzyme catalyzed the formation of 8.3 nmol FMN - min-1 - mg-1 at 37 degrees C and had apparent Km values for riboflavin and ATP of 10 and 4.7 micronM, respectively. ATP could be replaced by ADP (22% of the rate observed with ATP) but not by GTP. The enzyme also phosphorylated 5-deaza- and 8-bromoriboflavin with activities of 15 and 70%, respectively, of that with riboflavin; it was inactive with iso riboflavin and deoxyriboflavin.", "contents": "A continuous fluorometric assay for flavokinase. Properties of flavokinase from Peptostreptococcus elsdenii. A continuous fluorometric assay that utilizes apoflavodoxin as a trapping agent for riboflavin 5'-phosphate (FMN) has been developed for flavokinase (ATP:riboflavin 5'-phosphotransferase, EC 2.7.1.26). Use of this assay is illustrated in a procedure for the partial purification of flavokinase from the strict anaerobe Peptostreptococcus elsdenii. The purified enzyme catalyzed the formation of 8.3 nmol FMN - min-1 - mg-1 at 37 degrees C and had apparent Km values for riboflavin and ATP of 10 and 4.7 micronM, respectively. ATP could be replaced by ADP (22% of the rate observed with ATP) but not by GTP. The enzyme also phosphorylated 5-deaza- and 8-bromoriboflavin with activities of 15 and 70%, respectively, of that with riboflavin; it was inactive with iso riboflavin and deoxyriboflavin."}
{"id": "PMID:195620", "title": "Kynureninase-type enzymes and the evolution of the aerobic tryptophan-to-nicotinamide adenine dinucleotide pathway.", "content": "Kynureninase-type (L-kynurenine hydrolase, EC 3.7.1.3) activity has been found to be present in the livers of fish, amphibia, reptiles, and birds. In addition to past information concerning this enzyme activity in mammalian liver, it is now clear that all the major classes of vertebrates carry a highly specialized kynureninase-type enzyme, which we have termed a hydroxykynureninase. To compare the reactivities of these enzymes with L-kynurenine and L-3-hydroxykynurenine, ratios of tau values (Km/V) were used. Based on this comparison, the bacterium Pseudomonas fluorescens carries the most efficient kynureninase, whereas the amphibian Xenopus laevis has the most efficient hydroxykynureniase. In these two cases, the ratio of tau values differs by a factor of 38 000. It is hypothesized that the tryptophan-to-nicotinamide adenine dinucleotide biosynthetic pathway evolved from a catabolic system of enzymes, and that the differences observed in the kynureninase-type enzymes between lower and higher organisms reflect the specialization of the function of these enzymes from a strictly catabolic role to an anabolic one during the course of evolution.", "contents": "Kynureninase-type enzymes and the evolution of the aerobic tryptophan-to-nicotinamide adenine dinucleotide pathway. Kynureninase-type (L-kynurenine hydrolase, EC 3.7.1.3) activity has been found to be present in the livers of fish, amphibia, reptiles, and birds. In addition to past information concerning this enzyme activity in mammalian liver, it is now clear that all the major classes of vertebrates carry a highly specialized kynureninase-type enzyme, which we have termed a hydroxykynureninase. To compare the reactivities of these enzymes with L-kynurenine and L-3-hydroxykynurenine, ratios of tau values (Km/V) were used. Based on this comparison, the bacterium Pseudomonas fluorescens carries the most efficient kynureninase, whereas the amphibian Xenopus laevis has the most efficient hydroxykynureniase. In these two cases, the ratio of tau values differs by a factor of 38 000. It is hypothesized that the tryptophan-to-nicotinamide adenine dinucleotide biosynthetic pathway evolved from a catabolic system of enzymes, and that the differences observed in the kynureninase-type enzymes between lower and higher organisms reflect the specialization of the function of these enzymes from a strictly catabolic role to an anabolic one during the course of evolution."}
{"id": "PMID:195626", "title": "In vitro regulation of cholesterol metabolism by low density lipoproteins in skin fibroblasts from hypo-and hyperresponding squirrel monkeys.", "content": "When squirrel monkeys (Saimiri sciureus) are fed diets containing cholesterol, some individuals (hyperresponders) become hypercholesterolemic, while others (hyporesponders) are able to maintain nearly normal plasma cholesterol concentrations. Skin fibroblasts were grown from three hyperresponder and threehyporesponder squirrel monkeys, previously characterized on the basis of their plasma cholesterol response to two cholesterol-containing diets and the pheno-type of their parents. The rates of cholesterol synthesis and esterification were determined in the cultured fibroblasts incubated with low density lipoproteins isolated from normocholesterolemic squirrel monkeys or hypercholesterolemic rhesus monkeys. Both lipoprotein preparations influenced the metabolic parameters measured in a similar manner in cells from both hypo- and hyperresponder animals. Exposure of skin fibroblasts to low density lipoproteins resultd in a stimulation of cholesterol esterification and a suppression of cholesterol synthesis in cells from both hypo- and hyperresponder animals. When incubated with increasing concentrations of low density lipoprotein cholesterol, up to 50 microgram/ml, fibroblasts from both hypo-and hyperresponding animals responded with a similar maximum percentage suppression of sterol synthesis. Thus, hyperresponsiveness to dietary cholesterol in squirrel monkeys, although a heritable characteristic, is not associated with an inability of low density lipoprotein to suppress cholesterol synthesis or stimulate cholesterol esterification as occurs in familial hypercholesterolemia in man.", "contents": "In vitro regulation of cholesterol metabolism by low density lipoproteins in skin fibroblasts from hypo-and hyperresponding squirrel monkeys. When squirrel monkeys (Saimiri sciureus) are fed diets containing cholesterol, some individuals (hyperresponders) become hypercholesterolemic, while others (hyporesponders) are able to maintain nearly normal plasma cholesterol concentrations. Skin fibroblasts were grown from three hyperresponder and threehyporesponder squirrel monkeys, previously characterized on the basis of their plasma cholesterol response to two cholesterol-containing diets and the pheno-type of their parents. The rates of cholesterol synthesis and esterification were determined in the cultured fibroblasts incubated with low density lipoproteins isolated from normocholesterolemic squirrel monkeys or hypercholesterolemic rhesus monkeys. Both lipoprotein preparations influenced the metabolic parameters measured in a similar manner in cells from both hypo- and hyperresponder animals. Exposure of skin fibroblasts to low density lipoproteins resultd in a stimulation of cholesterol esterification and a suppression of cholesterol synthesis in cells from both hypo- and hyperresponder animals. When incubated with increasing concentrations of low density lipoprotein cholesterol, up to 50 microgram/ml, fibroblasts from both hypo-and hyperresponding animals responded with a similar maximum percentage suppression of sterol synthesis. Thus, hyperresponsiveness to dietary cholesterol in squirrel monkeys, although a heritable characteristic, is not associated with an inability of low density lipoprotein to suppress cholesterol synthesis or stimulate cholesterol esterification as occurs in familial hypercholesterolemia in man."}
{"id": "PMID:195627", "title": "Effects of cyclic nucleotides on the conformational states of the alpha core of the cyclic AMP receptor protein.", "content": "The alpha core gragment produced by limited proteolysis contains the cyclic AMP binding domain and the two buried sulfhydryl groups of the cyclic AMP receptor protein. The buried sulfhydryl groups of the alpha core react with 5,5'-dithio-bis(2-nitrobenzoic acid) after denaturation by 3 M urea or digestion with subtilisin. The rate of sulfhydryl modification in the presence of 3 M urea or subtilisin is markedly decreased in the presence of cyclic nucleotides which are proposed to tighten the conformation of the alpha core. Incubation of the alpha core in 3 M urea or dithionitrobenzoic acid does not affect cyclic AMP binding while dithionitrobenzoic acid plus 3 M urea inhibits cyclic AMP binding suggesting a role for the buried sulfhydryls in cyclic AMP binding or their proximity to the cyclic AMP binding domain of the alpha core. The data are consistent with a ligand-induced conformational change in the alpha region of the native cyclic AMP receptor protein that is required for DNA binding.", "contents": "Effects of cyclic nucleotides on the conformational states of the alpha core of the cyclic AMP receptor protein. The alpha core gragment produced by limited proteolysis contains the cyclic AMP binding domain and the two buried sulfhydryl groups of the cyclic AMP receptor protein. The buried sulfhydryl groups of the alpha core react with 5,5'-dithio-bis(2-nitrobenzoic acid) after denaturation by 3 M urea or digestion with subtilisin. The rate of sulfhydryl modification in the presence of 3 M urea or subtilisin is markedly decreased in the presence of cyclic nucleotides which are proposed to tighten the conformation of the alpha core. Incubation of the alpha core in 3 M urea or dithionitrobenzoic acid does not affect cyclic AMP binding while dithionitrobenzoic acid plus 3 M urea inhibits cyclic AMP binding suggesting a role for the buried sulfhydryls in cyclic AMP binding or their proximity to the cyclic AMP binding domain of the alpha core. The data are consistent with a ligand-induced conformational change in the alpha region of the native cyclic AMP receptor protein that is required for DNA binding."}
{"id": "PMID:195628", "title": "Particle distribution of human serum high density lipoproteins.", "content": "Density gradient ultracentrifugation of human serum high density lipoproteins (HDL) from both normolipemic males and females results in a distribution of HDL concentration versus subfraction hydrated density which has three maxima. Gradient gel electrophoresis of total HDL is characterized by three banding maxima, the positions of which suggest the presence of three particle size ranges: I. 10.8-12.0 nm, II. 9.7-10.7 nm, and III. 8.5-9.6 nm. Gradient gel electrophoresis of density gradient subfractions established an inverse relationship between particle size and particle hydrated density which was corroborated by electron microscopy and analytic ultracentrifugation. Comparison of male HDL from size ranges I, II, and III with female HDL from the same size ranges showed only small differences in the mean value of the peak F degrees 1.20 rate, size, molecular weight, protein weight percent, and weight protein/weight phospholipid. Major differences between males and females were seen in the relative amounts of HDL in density gradient subfractions 1-3 (size range I material) and 11-12 (size range III material); the percent total HDL in the group of subfractions 1-3 was greatly increased in female HDL while that of the group of subfractions 11-12 was increased in the male HDL. These studies indicate the presence of at least three major components in HDL instead of two (HDL2 and HDL3) and that peak F degrees 1.20 rate differences in HDL schlieren patterns between males and females are a function of the relative levels of these three components.", "contents": "Particle distribution of human serum high density lipoproteins. Density gradient ultracentrifugation of human serum high density lipoproteins (HDL) from both normolipemic males and females results in a distribution of HDL concentration versus subfraction hydrated density which has three maxima. Gradient gel electrophoresis of total HDL is characterized by three banding maxima, the positions of which suggest the presence of three particle size ranges: I. 10.8-12.0 nm, II. 9.7-10.7 nm, and III. 8.5-9.6 nm. Gradient gel electrophoresis of density gradient subfractions established an inverse relationship between particle size and particle hydrated density which was corroborated by electron microscopy and analytic ultracentrifugation. Comparison of male HDL from size ranges I, II, and III with female HDL from the same size ranges showed only small differences in the mean value of the peak F degrees 1.20 rate, size, molecular weight, protein weight percent, and weight protein/weight phospholipid. Major differences between males and females were seen in the relative amounts of HDL in density gradient subfractions 1-3 (size range I material) and 11-12 (size range III material); the percent total HDL in the group of subfractions 1-3 was greatly increased in female HDL while that of the group of subfractions 11-12 was increased in the male HDL. These studies indicate the presence of at least three major components in HDL instead of two (HDL2 and HDL3) and that peak F degrees 1.20 rate differences in HDL schlieren patterns between males and females are a function of the relative levels of these three components."}
{"id": "PMID:195629", "title": "Dimeric (\"big\") human placental lactogen. Immunological and biological activity.", "content": "Dimeric (\"big\") human placental lactogen has been isolated in near homogeneous form from placental tissue. It consists of a disulfide-linked (stable) form and a noncovalently associated (unstable) form of the native hormone. The two forms were separated by exposure to denaturing conditions and resolution by gel exclusion chromatography. Both forms retained immunological activity, ability to bind mammary membranes, and ability to induce mammary N-acetyllactosamine synthetase in vitro. On a molar basis, stable dimeric placental lactogen was more active than placental lactogen in the radioimmunoassay indicating that the immunological determinants on both monomeric units could bind to antibody. On a molar basis, stable dimeric placental lactogen was equally active with monomeric placental lactogen in competing for mammary gland membrane binding sites, indicating that only one active site in the molecule could interact with the membrane at a time. Stable dimeric placental lactogen was also active in an in vitro bioassay using the induction of N-acetyllactosamine synthetase. It is concluded that dimer formation does not alter the biologically active portion of the placental lactogen molecule. Since the carboxyl-terminal region (residues 182-191) is involved in the interchain disulfide bonds of dimeric placental lactogen, this portion of the molecule is probably not necessary for its biological activity.", "contents": "Dimeric (\"big\") human placental lactogen. Immunological and biological activity. Dimeric (\"big\") human placental lactogen has been isolated in near homogeneous form from placental tissue. It consists of a disulfide-linked (stable) form and a noncovalently associated (unstable) form of the native hormone. The two forms were separated by exposure to denaturing conditions and resolution by gel exclusion chromatography. Both forms retained immunological activity, ability to bind mammary membranes, and ability to induce mammary N-acetyllactosamine synthetase in vitro. On a molar basis, stable dimeric placental lactogen was more active than placental lactogen in the radioimmunoassay indicating that the immunological determinants on both monomeric units could bind to antibody. On a molar basis, stable dimeric placental lactogen was equally active with monomeric placental lactogen in competing for mammary gland membrane binding sites, indicating that only one active site in the molecule could interact with the membrane at a time. Stable dimeric placental lactogen was also active in an in vitro bioassay using the induction of N-acetyllactosamine synthetase. It is concluded that dimer formation does not alter the biologically active portion of the placental lactogen molecule. Since the carboxyl-terminal region (residues 182-191) is involved in the interchain disulfide bonds of dimeric placental lactogen, this portion of the molecule is probably not necessary for its biological activity."}
{"id": "PMID:195630", "title": "Properties of human erythrocyte phosphatidylinositol kinase and inhibition by adenosine, ADP and related compounds.", "content": "1. An improved assay for the enzyme phosphatidylinositol kinase is described. The kinase activity is increased more than 10-fold by the addition of mercaptoethanol and exogenous phosphatidylinositol in the presence of Triton X-100. The enzyme is solubilized by non-ionic detergents. 2. Phosphatidylinositol kinase is inhibited by physiological concentrations of ADP and by similar levels of adenosine. Cyclic AMP, AMP and theophylline inhibit at higher concentrations. Caffeine is much less effective than theophylline as an inhibitor. Guanine nucleotides do not appreciably inhibit the kinase. All the inhibitors tested seemed to compete with ATP. Theophylline also reduced the rate of polyphosphoinositide synthesis in intact cells. 3. Possible roles of polyphosphoinositides in energy charge maintenance and inversion and resealing are discussed.", "contents": "Properties of human erythrocyte phosphatidylinositol kinase and inhibition by adenosine, ADP and related compounds. 1. An improved assay for the enzyme phosphatidylinositol kinase is described. The kinase activity is increased more than 10-fold by the addition of mercaptoethanol and exogenous phosphatidylinositol in the presence of Triton X-100. The enzyme is solubilized by non-ionic detergents. 2. Phosphatidylinositol kinase is inhibited by physiological concentrations of ADP and by similar levels of adenosine. Cyclic AMP, AMP and theophylline inhibit at higher concentrations. Caffeine is much less effective than theophylline as an inhibitor. Guanine nucleotides do not appreciably inhibit the kinase. All the inhibitors tested seemed to compete with ATP. Theophylline also reduced the rate of polyphosphoinositide synthesis in intact cells. 3. Possible roles of polyphosphoinositides in energy charge maintenance and inversion and resealing are discussed."}
{"id": "PMID:195631", "title": "Effects of polyamines and polyanions on a cyclic nucleotide-independent and a cyclic AMP-dependent protein kinase.", "content": "The phosphorylation of phosvitin in vitro by a cyclic nucleotide-independent protein kinase (phosvitin kinase) derived from rooster liver is markedly stimulated by the divalent cation, Mg2+. In addition, the activity is further stimulated by low concentrations of the polyamines putrescine, spermidine and spermine leading to higher rates of phosphate incorporation than could be obtained at any concentration of Mg2+. Spermine is inhibitory at higher concentrations. The polyamines shift the Mg2+ requirement for maximal activity to lower concentrations. The activity of a cyclic AMP-dependent histone kinase from beef heart is not altered by the presence of polyamines. Heparin is a potent inhibitor of phosvitin kinase but has no effect on histone kinase. Polyribonucleotides (polyadenylic acid and transfer RNA) inhibit both types of kinases, but the degree of inhibition of phosvitin kinase is variable and depends upon the type of the polyanion present. Sermidine and spermine, but not Mg2+, efficiently counteract the inhibitory action of heparin and tRNA. The results suggest that, also in vivo, naturally occurring polyamines and polyanions such as tRNA may have a regulatory function on protein kinases.", "contents": "Effects of polyamines and polyanions on a cyclic nucleotide-independent and a cyclic AMP-dependent protein kinase. The phosphorylation of phosvitin in vitro by a cyclic nucleotide-independent protein kinase (phosvitin kinase) derived from rooster liver is markedly stimulated by the divalent cation, Mg2+. In addition, the activity is further stimulated by low concentrations of the polyamines putrescine, spermidine and spermine leading to higher rates of phosphate incorporation than could be obtained at any concentration of Mg2+. Spermine is inhibitory at higher concentrations. The polyamines shift the Mg2+ requirement for maximal activity to lower concentrations. The activity of a cyclic AMP-dependent histone kinase from beef heart is not altered by the presence of polyamines. Heparin is a potent inhibitor of phosvitin kinase but has no effect on histone kinase. Polyribonucleotides (polyadenylic acid and transfer RNA) inhibit both types of kinases, but the degree of inhibition of phosvitin kinase is variable and depends upon the type of the polyanion present. Sermidine and spermine, but not Mg2+, efficiently counteract the inhibitory action of heparin and tRNA. The results suggest that, also in vivo, naturally occurring polyamines and polyanions such as tRNA may have a regulatory function on protein kinases."}
{"id": "PMID:195632", "title": "Elevation of guanosine 3',5'-monophosphate level by adenosine in cerebellar slices of guinea pig.", "content": "Effect of adenosine on the level of guanosine 3',5'-monophosphate in guinea pig cerebellar slices was investigated. Adenosine increased the concentration of guanosine 3',5'-monophosphate in the slices 3--4 fold. Upon removal of adenosine from the medium, the concentration of guanosine 3',5'-monophosphate returned to the initial level. AMP, ADP or ATP also increased the guanosine 3',5'-monophosphate level to the same extent as adenosine, while adenine or other nucleosides were not effective. In the absence of Ca2+ in the incubation medium, adenosine did not increase the concentration of guanosine 3',5'-monophosphate in cerebellar slices although level of adenosine 3',5'-monophosphate was elevated by adenosine. Anticholinergic agents, adrenergic blocking agents or antihistaminics did not prevent the increase of guanosine 3',5'-monophosphate by adenosine indicating that the effect of adenosine was not mediated by the release of neurotransmitters. The combination of adenosine with depolarizing agents showed an additive effect on the level of guanosine 3',5'-monophosphate indicating that adenosine increased the level of guanosine 3',5'-monophosphate by a different mechanism from the depolarization.", "contents": "Elevation of guanosine 3',5'-monophosphate level by adenosine in cerebellar slices of guinea pig. Effect of adenosine on the level of guanosine 3',5'-monophosphate in guinea pig cerebellar slices was investigated. Adenosine increased the concentration of guanosine 3',5'-monophosphate in the slices 3--4 fold. Upon removal of adenosine from the medium, the concentration of guanosine 3',5'-monophosphate returned to the initial level. AMP, ADP or ATP also increased the guanosine 3',5'-monophosphate level to the same extent as adenosine, while adenine or other nucleosides were not effective. In the absence of Ca2+ in the incubation medium, adenosine did not increase the concentration of guanosine 3',5'-monophosphate in cerebellar slices although level of adenosine 3',5'-monophosphate was elevated by adenosine. Anticholinergic agents, adrenergic blocking agents or antihistaminics did not prevent the increase of guanosine 3',5'-monophosphate by adenosine indicating that the effect of adenosine was not mediated by the release of neurotransmitters. The combination of adenosine with depolarizing agents showed an additive effect on the level of guanosine 3',5'-monophosphate indicating that adenosine increased the level of guanosine 3',5'-monophosphate by a different mechanism from the depolarization."}
{"id": "PMID:195634", "title": "Comparative EPR study on high-spin ferric porphine complexes and cytochrome P-450 having rhombic character.", "content": "Comparative EPR studies were made on two high-spin Fe(III) porphine model systems and mammalian liver microsomal cytochromes P-450, all of which exhibit approximately the same degrees of rhombicity in their EPR spectra. Comparison of g values and linewidths as a function of temperature, and of the microwave power saturation demonstrated that EPR characteristics of P-450 are more similar to the Fe(III) porphines having the thiolate axial ligand than in the other model systems, the mixed crystals of Fe(III) porphine with the corresponding free base porphine, in which no thiolate ligand is involved. There is, however, a discrepancy between P-450 and the model thiolates with respect to the size of the zero-field parameter D. These observations indicate that P-450 heme has essential structural features in common with thiolates but the Fe-S bond of P-450 may be modified from its normal orientation in model thiolates, probably as a result of the constraints imposed by the protein structure.", "contents": "Comparative EPR study on high-spin ferric porphine complexes and cytochrome P-450 having rhombic character. Comparative EPR studies were made on two high-spin Fe(III) porphine model systems and mammalian liver microsomal cytochromes P-450, all of which exhibit approximately the same degrees of rhombicity in their EPR spectra. Comparison of g values and linewidths as a function of temperature, and of the microwave power saturation demonstrated that EPR characteristics of P-450 are more similar to the Fe(III) porphines having the thiolate axial ligand than in the other model systems, the mixed crystals of Fe(III) porphine with the corresponding free base porphine, in which no thiolate ligand is involved. There is, however, a discrepancy between P-450 and the model thiolates with respect to the size of the zero-field parameter D. These observations indicate that P-450 heme has essential structural features in common with thiolates but the Fe-S bond of P-450 may be modified from its normal orientation in model thiolates, probably as a result of the constraints imposed by the protein structure."}
{"id": "PMID:195638", "title": "Preparation and metabolic characterization of isolated rat lung cells.", "content": "Collagenase digestion of minced lung tissue yielded isolated cells, functionally viable as judged by several metabolic and morphological criteria, representative of all the cell species normally present in the tissue. The efficiency of the isolation procedure was about 25 per cent. Aerobic metabolism was not affected by most of the substrates tested except by succinate which increased oxygen utilization, and glucose, fructose and octanoate which significantly decreased oxygen uptake. Since no significant changes have been observed in the cellular adenine nucleotide content during glucose depression of aerobic metabolism it is concluded that the glycolytic flux had to be sufficient as to account for the decrease in the mitochondrial energy production. The mechanism responsible for these effects as well as their physiological significance are discussed herewith.", "contents": "Preparation and metabolic characterization of isolated rat lung cells. Collagenase digestion of minced lung tissue yielded isolated cells, functionally viable as judged by several metabolic and morphological criteria, representative of all the cell species normally present in the tissue. The efficiency of the isolation procedure was about 25 per cent. Aerobic metabolism was not affected by most of the substrates tested except by succinate which increased oxygen utilization, and glucose, fructose and octanoate which significantly decreased oxygen uptake. Since no significant changes have been observed in the cellular adenine nucleotide content during glucose depression of aerobic metabolism it is concluded that the glycolytic flux had to be sufficient as to account for the decrease in the mitochondrial energy production. The mechanism responsible for these effects as well as their physiological significance are discussed herewith."}
{"id": "PMID:195640", "title": "Sequential enzymolysis of human aorta and resultant stress-strain behavior.", "content": "The human aorta has five major components from which the aortic walls can be characterized: mucopolysaccharides, smooth muscle, collagen, micro-fibrilar glycoprotein (associated with the elastic fiber), and elastin. Enzymes were employed to remove four of the components sequentially without destroying the mechanical characteristics of the remaining components in order to elucidate the structure-property relationship in the human aorta. Before treatment the initial mechanical behavior was recorded on an Instron Tensile testing machine. After enzymolysis the samples and controls were again tested and these results compared to their prior characteristics. Stress-strain characteristics after a sequence of enzyme treatments indicate that two of the components share the major part of the stress in the circumferential direction. These components, elastin and collagen, contribute as if they were in parallel to each other with the collagen in a crimped state.", "contents": "Sequential enzymolysis of human aorta and resultant stress-strain behavior. The human aorta has five major components from which the aortic walls can be characterized: mucopolysaccharides, smooth muscle, collagen, micro-fibrilar glycoprotein (associated with the elastic fiber), and elastin. Enzymes were employed to remove four of the components sequentially without destroying the mechanical characteristics of the remaining components in order to elucidate the structure-property relationship in the human aorta. Before treatment the initial mechanical behavior was recorded on an Instron Tensile testing machine. After enzymolysis the samples and controls were again tested and these results compared to their prior characteristics. Stress-strain characteristics after a sequence of enzyme treatments indicate that two of the components share the major part of the stress in the circumferential direction. These components, elastin and collagen, contribute as if they were in parallel to each other with the collagen in a crimped state."}
{"id": "PMID:195641", "title": "Electron paramagnetic resonance of Cu2+:Mb single crystal. Conformational changes.", "content": "Copper introduced into met-myoglobin crystals occupies various sites as indicated by electron paramagnetic resonance parameters. Cu2+ (A) is probably liganded to histidine A10, lysine A14, and asparagine GH4 (Banaszak et al., 1965) and shows superhyperfine interaction with a single (imidazole) nitrogen. Cu2+ (B) and Cu2+ (C) correspond to other anisotropic sites described in less detail. Cu2+ (A) exhibits a transition to an isotropic form with a transition temperature of 40.5 degrees C. This transition indicates a conformational change in myoglobin and could correspond to a motion of A helix away from the GH section. The transition temperature is 7 degrees C higher than the one previously reported (Atanasov, 1971) for myoglobin in solution.", "contents": "Electron paramagnetic resonance of Cu2+:Mb single crystal. Conformational changes. Copper introduced into met-myoglobin crystals occupies various sites as indicated by electron paramagnetic resonance parameters. Cu2+ (A) is probably liganded to histidine A10, lysine A14, and asparagine GH4 (Banaszak et al., 1965) and shows superhyperfine interaction with a single (imidazole) nitrogen. Cu2+ (B) and Cu2+ (C) correspond to other anisotropic sites described in less detail. Cu2+ (A) exhibits a transition to an isotropic form with a transition temperature of 40.5 degrees C. This transition indicates a conformational change in myoglobin and could correspond to a motion of A helix away from the GH section. The transition temperature is 7 degrees C higher than the one previously reported (Atanasov, 1971) for myoglobin in solution."}
{"id": "PMID:195642", "title": "Collective behaviour of hemoglobin in dense solutions.", "content": "The formation of radical pairs of spin-labelled hemoglobin molecules (beta-93 cysteine) in a mixture with unlabelled hemoglobin of concentrations higher than the critical one [(5.7 less than c less than 6.3) mM/sigma per heme] is due to some kind of long-range order characterizing these solutions. Labelled molecules induce pertubation in an unlabelled hemoglobin solution of concentration higher than the critical one. The collective behaviour of unlabelled molecules gives rise to the formation of radical pairs of spin-labelled hemoglobin molecules. Such behaviour is dependent on the ligand bound at the heme iron (carbonmonoxide, oxygen, or water.)", "contents": "Collective behaviour of hemoglobin in dense solutions. The formation of radical pairs of spin-labelled hemoglobin molecules (beta-93 cysteine) in a mixture with unlabelled hemoglobin of concentrations higher than the critical one [(5.7 less than c less than 6.3) mM/sigma per heme] is due to some kind of long-range order characterizing these solutions. Labelled molecules induce pertubation in an unlabelled hemoglobin solution of concentration higher than the critical one. The collective behaviour of unlabelled molecules gives rise to the formation of radical pairs of spin-labelled hemoglobin molecules. Such behaviour is dependent on the ligand bound at the heme iron (carbonmonoxide, oxygen, or water.)"}
{"id": "PMID:195647", "title": "[Participation of the adenylate cyclase system in inductive synthesis of acetylcholinesterase in the brain].", "content": "The enhancement of the brain acetyl cholinesterase (ACHE) activity in rats by the intraventricular injection of adrenaline or dibutiryl analogue cyclic adenosine-3',5'-monophosphate (cAMP) was shown to be due to the enzyme inductive synthesis. ACHE induction manifests itself more in the subcortical white matter than in the cortex. The stimulating effect of adrenaline on the ACHE activity is suppressed under the beta-adrenoreceptor block, while the cAMP effect remains unchanged. On the contrary, the block of the alpha-adrenoreceptors stimulates the enzyme synthesis induction. The effects of adrenaline and cAMP are of the same direction and are realized through the beta-adrenoreceptors. The enhancement of ACHE activity during the block of the alpha-adrenoreceptors is accounted for by the elimination of their inhibitory influence on the beta-adrenoreceptors.", "contents": "[Participation of the adenylate cyclase system in inductive synthesis of acetylcholinesterase in the brain]. The enhancement of the brain acetyl cholinesterase (ACHE) activity in rats by the intraventricular injection of adrenaline or dibutiryl analogue cyclic adenosine-3',5'-monophosphate (cAMP) was shown to be due to the enzyme inductive synthesis. ACHE induction manifests itself more in the subcortical white matter than in the cortex. The stimulating effect of adrenaline on the ACHE activity is suppressed under the beta-adrenoreceptor block, while the cAMP effect remains unchanged. On the contrary, the block of the alpha-adrenoreceptors stimulates the enzyme synthesis induction. The effects of adrenaline and cAMP are of the same direction and are realized through the beta-adrenoreceptors. The enhancement of ACHE activity during the block of the alpha-adrenoreceptors is accounted for by the elimination of their inhibitory influence on the beta-adrenoreceptors."}
{"id": "PMID:195648", "title": "[Possible participation of prostaglandins A1 and B1 in the development of internal carotid artery spasm].", "content": "Experiments were carried out on dogs with the internal carotid artery circulatory isolated and continuously perfused in situ with oxygenated Ringer-Krebs bicarbonate solution. Prostaglandins A1 and B1 (PG-A1 and PG-B1) exerted a constrictory effect on the artery. The effect of both prostaglandins was significantly less, but more prolonged than that of the same doses of serotonin. A possible role of PG-A1 and PG-B1 in the development of vasospasm is testified to by the following experimental results: a) during repeated action of PG-A1 AND PG-B1 their effect did not change, and therefore it should not decrease under prolonged influence of these prostaglandins on the vascular wall;) b) the mentioned prostaglandins caused potentiation of the constrictory effect of both serotonin and norepinephrine.", "contents": "[Possible participation of prostaglandins A1 and B1 in the development of internal carotid artery spasm]. Experiments were carried out on dogs with the internal carotid artery circulatory isolated and continuously perfused in situ with oxygenated Ringer-Krebs bicarbonate solution. Prostaglandins A1 and B1 (PG-A1 and PG-B1) exerted a constrictory effect on the artery. The effect of both prostaglandins was significantly less, but more prolonged than that of the same doses of serotonin. A possible role of PG-A1 and PG-B1 in the development of vasospasm is testified to by the following experimental results: a) during repeated action of PG-A1 AND PG-B1 their effect did not change, and therefore it should not decrease under prolonged influence of these prostaglandins on the vascular wall;) b) the mentioned prostaglandins caused potentiation of the constrictory effect of both serotonin and norepinephrine."}
{"id": "PMID:195649", "title": "[Factors influencing the serum levels of cholesterol and beta-lipoproteins in starving rabbits].", "content": "The influence of starvation on the lipid metabolism was studied on male rabbits under usual conditions and in the presence of pyroxidine deficiency (4-deoxypyridoxine administration) and of thiamine (oxythiamine administration), and also in administration of neurotropic preparations (phenamine, seduxen). Starvation for 7 to 10 days led to increase of cholesterol and beta-lipoproteins level in the serum. Pyridoxine deficiency and phenamine administration caused a greater increase of cholesterol and especially or beta-lipoproteins. On the other hand, thiamine deficiency and seduxen administration limited an increase of cholesterol and beta-lipoproteins during hungry stress. Administration of aerovit for prophylactic purpose promoted a decrease of the metabolic shifts. The amount of cholesterol increased in the liver of hungry animals, especially after the phenamine administration and in the presence of pyridoxine deficiency; aerovit administration prevented increased cholesterol accumulation in the liver. The differences in the cholesterol level in the serum and and the liver can be explained by the changes of its biosynthesis during hungry stress.", "contents": "[Factors influencing the serum levels of cholesterol and beta-lipoproteins in starving rabbits]. The influence of starvation on the lipid metabolism was studied on male rabbits under usual conditions and in the presence of pyroxidine deficiency (4-deoxypyridoxine administration) and of thiamine (oxythiamine administration), and also in administration of neurotropic preparations (phenamine, seduxen). Starvation for 7 to 10 days led to increase of cholesterol and beta-lipoproteins level in the serum. Pyridoxine deficiency and phenamine administration caused a greater increase of cholesterol and especially or beta-lipoproteins. On the other hand, thiamine deficiency and seduxen administration limited an increase of cholesterol and beta-lipoproteins during hungry stress. Administration of aerovit for prophylactic purpose promoted a decrease of the metabolic shifts. The amount of cholesterol increased in the liver of hungry animals, especially after the phenamine administration and in the presence of pyridoxine deficiency; aerovit administration prevented increased cholesterol accumulation in the liver. The differences in the cholesterol level in the serum and and the liver can be explained by the changes of its biosynthesis during hungry stress."}
{"id": "PMID:195650", "title": "[Inhibition of rat heart and brain cyclic adenosine-3',5'-monophosphate phosphodiesterase in vitro under the influence of neurohormone C].", "content": "The work was devoted to one of the new neurohormones (neurohormone \"C\") obtained from the bovine hypothalamus which produced a pronounced relaxation of the coronary vessels. A study of the effect of \"C\" on cyclic 3',5'-adenosine monophosphate (cAMP) phosphodiesterase (PDE) showed \"C\" to be a potent inhibitor of PDE in the crude PDE-preparations of the rat heart and brain. Experiments were carried out on the 2000 g supernatant obtained from the homogenized tissues. It is supposed that the relaxant effect of \"C\" on the coronary vessels is due to its inhibitory action on PDE mediated by the accumulated cAMP.", "contents": "[Inhibition of rat heart and brain cyclic adenosine-3',5'-monophosphate phosphodiesterase in vitro under the influence of neurohormone C]. The work was devoted to one of the new neurohormones (neurohormone \"C\") obtained from the bovine hypothalamus which produced a pronounced relaxation of the coronary vessels. A study of the effect of \"C\" on cyclic 3',5'-adenosine monophosphate (cAMP) phosphodiesterase (PDE) showed \"C\" to be a potent inhibitor of PDE in the crude PDE-preparations of the rat heart and brain. Experiments were carried out on the 2000 g supernatant obtained from the homogenized tissues. It is supposed that the relaxant effect of \"C\" on the coronary vessels is due to its inhibitory action on PDE mediated by the accumulated cAMP."}
{"id": "PMID:195651", "title": "[Functioning of the lactose operon of E. coli K-12 under the influence of non-specific regulators].", "content": "A possible role played by cAMP in the stimulating action of ACTH and hydrocortisone on lactose E. coli K-12 operon was studied. It was shown that ACTH caused no effect in the E. coli WZ-78/F'lac (cya855) and E. coli CA8001 (L1) strains with destroyed positive cAMP control system of the lactose operon function, at the same time producing a stimulating effect on the lactose operon in the strains of wild type, i.e. E coli 200PS/F'lac and E. coli 3000. Hydrocortisone stimulated the lactose operon function both in E. coli 3000 and in the mutant E. coli CA8001 (L1). It was supposed that the accelerating effect of ACTH on the lactose operon was mediated through cAMP; as to hydrocortisone--it stimulated the lactose operon function independently of cAMP.", "contents": "[Functioning of the lactose operon of E. coli K-12 under the influence of non-specific regulators]. A possible role played by cAMP in the stimulating action of ACTH and hydrocortisone on lactose E. coli K-12 operon was studied. It was shown that ACTH caused no effect in the E. coli WZ-78/F'lac (cya855) and E. coli CA8001 (L1) strains with destroyed positive cAMP control system of the lactose operon function, at the same time producing a stimulating effect on the lactose operon in the strains of wild type, i.e. E coli 200PS/F'lac and E. coli 3000. Hydrocortisone stimulated the lactose operon function both in E. coli 3000 and in the mutant E. coli CA8001 (L1). It was supposed that the accelerating effect of ACTH on the lactose operon was mediated through cAMP; as to hydrocortisone--it stimulated the lactose operon function independently of cAMP."}
{"id": "PMID:195652", "title": "Evidence for intracellular amyloid formation in myeloma.", "content": "Evidence for intracellular formation of amyloid fibrils in a patient with kappa light-chain myeloma is described. Amyloid fibrils were seen as intracytoplasmic inclusions within plasma cells, histiocytes, renal tubule cells, and possibly in hepatocytes. Extracellular amyloid was also present. The electron microscopic studies suggest that amyloid fibrils may form in the Golgi apparatus and within lysosomes.", "contents": "Evidence for intracellular amyloid formation in myeloma. Evidence for intracellular formation of amyloid fibrils in a patient with kappa light-chain myeloma is described. Amyloid fibrils were seen as intracytoplasmic inclusions within plasma cells, histiocytes, renal tubule cells, and possibly in hepatocytes. Extracellular amyloid was also present. The electron microscopic studies suggest that amyloid fibrils may form in the Golgi apparatus and within lysosomes."}
{"id": "PMID:195653", "title": "Ultrastructural, cytochemical, and membrane surface marker characteristics of the atypical lymphocytes in infectious mononucleosis.", "content": "Atypical lymphocytes from nine young adults with acute infectious mononucleosis (IM) were studied for morphologic, ultrastructural, cytochemical, and membrane surface marker characteristics. There was an absolute increase in T lymphocytes in the patients. Atypical lymphocytes accounted for 83%-96% of the lymphocyte population. These lymphocytes contained cytoplasmic inclusions which ranged in size from 1000 to 6000 A, were usually membrane bound, and consisted of parallel arrays of microtubulelike structures. The inclusions, which have been referred to as parallel tubular arrays (PTA), were found in 15%-75% of the lymphocytes from the IM patients. Ultrastructural cytochemical methods demonstrated acid phosphatase activity within many of the membrane-bound PTA. The function of the PTA is unknown. Since they were observed only in the lymphocytes which appeared to correspond to the atypical lymphocytes on light microscopy, the majority of which typed as T cells, there appears to be an association between PTA and T lymphocytes. It is possible that PTA identify a specific subset of T lymphocytes which is expanded in IM. Alternatively, PTA may be a transient finding in lymphocytes appearing only in certain biologic states of the cell such as during T-lymphocyte activation.", "contents": "Ultrastructural, cytochemical, and membrane surface marker characteristics of the atypical lymphocytes in infectious mononucleosis. Atypical lymphocytes from nine young adults with acute infectious mononucleosis (IM) were studied for morphologic, ultrastructural, cytochemical, and membrane surface marker characteristics. There was an absolute increase in T lymphocytes in the patients. Atypical lymphocytes accounted for 83%-96% of the lymphocyte population. These lymphocytes contained cytoplasmic inclusions which ranged in size from 1000 to 6000 A, were usually membrane bound, and consisted of parallel arrays of microtubulelike structures. The inclusions, which have been referred to as parallel tubular arrays (PTA), were found in 15%-75% of the lymphocytes from the IM patients. Ultrastructural cytochemical methods demonstrated acid phosphatase activity within many of the membrane-bound PTA. The function of the PTA is unknown. Since they were observed only in the lymphocytes which appeared to correspond to the atypical lymphocytes on light microscopy, the majority of which typed as T cells, there appears to be an association between PTA and T lymphocytes. It is possible that PTA identify a specific subset of T lymphocytes which is expanded in IM. Alternatively, PTA may be a transient finding in lymphocytes appearing only in certain biologic states of the cell such as during T-lymphocyte activation."}
{"id": "PMID:195655", "title": "Synovial sarcoma of the soft parts in the 1st toe: recurrence after a 35 year interval.", "content": "A female patient with a recurrent synovial sarcoma of right 1st toe (35 years) after the first operation is presented. The histology of the tumor 35 years ago showed evidence of the biphasic structure, while the recurrent tumor contained only the fibrous elements. The patient has been examined 3 years after the last operation. She has no pain and there is no evidence of any recurrence. The patient refuses any radiation or additional surgery at this time.", "contents": "Synovial sarcoma of the soft parts in the 1st toe: recurrence after a 35 year interval. A female patient with a recurrent synovial sarcoma of right 1st toe (35 years) after the first operation is presented. The histology of the tumor 35 years ago showed evidence of the biphasic structure, while the recurrent tumor contained only the fibrous elements. The patient has been examined 3 years after the last operation. She has no pain and there is no evidence of any recurrence. The patient refuses any radiation or additional surgery at this time."}
{"id": "PMID:195659", "title": "The generation of nerve and muscle repetivie activity in the rat phrenic nerve-diaphragm preparation following inhibition of cholinesterase by ecothiopate.", "content": "1 Simultaneous extracellular recordings were made from two end-plate zones of the isolated diaphragm and from the phrenic nerve of the rat in response to stimulation of the nerve. The contractions of the diaphragm were also recorded.2 In the curarized diaphragm, the introduction of ecothiopate, a non-competitive inhibitor of cholinesterase, caused a threefold increase in the amplitude of the end-plate current and an eightfold increase in the duration at half the peak amplitude.3 In the non-curarized diaphragm, the introduction of ecothiopate caused the generation of repetitive activity (RA) in first the phrenic nerve: this was then followed by RA in the diaphragm. At that stage, nerve RA possessed a shorter latency than muscle RA. The generation time for nerve RA was 1.6 ms and for mRA, it was 2.7 milliseconds.4 Nerve RA was more labile than muscle RA; it was readily abolished by increasing the frequency of stimulation, by magnesium, by tubocurarine or by high concentrations of ecothiopate, whereas muscle RA was still generated. Steady exposure to acetylcholine abolished both forms of RA.5 Two competitive inhibitors of cholinesterase, neostigmine and ambenonium, were also shown to evoke RA in nerve and muscle. The generation times for nerve RA and muscle RA were similar to those following ecothiopate.6 It was concluded that nerve RA and muscle RA were generated after the inhibition of cholinesterase by ecothiopate as a result of the prolonged action of acetylcholine upon cholinoceptive sites on the nerve terminal and motor endplate respectively. A direct excitatory action of ecothiopate upon the phrenic nerve terminals was excluded.", "contents": "The generation of nerve and muscle repetivie activity in the rat phrenic nerve-diaphragm preparation following inhibition of cholinesterase by ecothiopate. 1 Simultaneous extracellular recordings were made from two end-plate zones of the isolated diaphragm and from the phrenic nerve of the rat in response to stimulation of the nerve. The contractions of the diaphragm were also recorded.2 In the curarized diaphragm, the introduction of ecothiopate, a non-competitive inhibitor of cholinesterase, caused a threefold increase in the amplitude of the end-plate current and an eightfold increase in the duration at half the peak amplitude.3 In the non-curarized diaphragm, the introduction of ecothiopate caused the generation of repetitive activity (RA) in first the phrenic nerve: this was then followed by RA in the diaphragm. At that stage, nerve RA possessed a shorter latency than muscle RA. The generation time for nerve RA was 1.6 ms and for mRA, it was 2.7 milliseconds.4 Nerve RA was more labile than muscle RA; it was readily abolished by increasing the frequency of stimulation, by magnesium, by tubocurarine or by high concentrations of ecothiopate, whereas muscle RA was still generated. Steady exposure to acetylcholine abolished both forms of RA.5 Two competitive inhibitors of cholinesterase, neostigmine and ambenonium, were also shown to evoke RA in nerve and muscle. The generation times for nerve RA and muscle RA were similar to those following ecothiopate.6 It was concluded that nerve RA and muscle RA were generated after the inhibition of cholinesterase by ecothiopate as a result of the prolonged action of acetylcholine upon cholinoceptive sites on the nerve terminal and motor endplate respectively. A direct excitatory action of ecothiopate upon the phrenic nerve terminals was excluded."}
{"id": "PMID:195660", "title": "Cyclic adenosine 3',5'-monophosphate and leucocyte chemotaxis in vivo.", "content": "1 The effect of local elevation of leucocyte cyclic adenosine 3',5'-monophosphate (cyclic AMP) content on the continued migration of leucocytes to a site of acute inflammation was studied in the pleural cavity of rats. 2 Leucocyte cyclic AMP levels were elevated by injecting with the irritant into the pleural cavity dibutyryl cyclic AMP alone or with theophylline. 3 The treatments both produced a marked reduction in leucocyte migration into a pleural reaction induced by immediate hypersensitivity, but had no effect on cell numbers in pleurisy induced either by pyrophosphate or urate crystals.", "contents": "Cyclic adenosine 3',5'-monophosphate and leucocyte chemotaxis in vivo. 1 The effect of local elevation of leucocyte cyclic adenosine 3',5'-monophosphate (cyclic AMP) content on the continued migration of leucocytes to a site of acute inflammation was studied in the pleural cavity of rats. 2 Leucocyte cyclic AMP levels were elevated by injecting with the irritant into the pleural cavity dibutyryl cyclic AMP alone or with theophylline. 3 The treatments both produced a marked reduction in leucocyte migration into a pleural reaction induced by immediate hypersensitivity, but had no effect on cell numbers in pleurisy induced either by pyrophosphate or urate crystals."}
{"id": "PMID:195661", "title": "The role of beta-adrenoceptors in the responses of the hepatic arterial vascular bed of the dog to phenylephrine, isoprenaline, noradrenaline and adrenaline.", "content": "1 The sympathetically-innervated hepatic arterial vascular bed of the dog was perfused from a femoral artery. Hepatic arterial blood flow and perfusion pressure were recorded continuously, and the hepatic arterial vascular resistance (HAVR) calculated from these measurements.2 Intra-arterial injections of phenylephrine caused dose-dependent rises in HAVR, indicating hepatic arterial vasoconstriction, at all doses above threshold. No secondary reductions in HAVR followed these responses.3 Intra-arterial injections of isoprenaline caused only dose-dependent reductions in HAVR at doses above threshold.4 Intra-arterial injections of noradrenaline typically caused an initial increase in HAVR which was followed at all but the highest doses by a secondary, delayed, reduction in HAVR.5 Intra-arterial injections of adrenaline, like those of noradrenaline, resulted in hepatic arterial vasoconstriction followed by hepatic arterial vasodilatation.6 On a molar basis, the most potent hepatic arterial vasoconstrictor was noradrenaline, followed by adrenaline and phenylephrine.7 The maximum reductions in HAVR caused by adrenaline (mean reduction = 21.9%) and noradrenaline (16.9%) were significantly smaller than those due to isoprenaline ((P) < 0.001).8 Propranolol attenuated the hepatic arterial vasodilator responses due to isoprenaline, and the secondary falls in HAVR following intra-arterial adrenaline and noradrenaline.9 Propranolol did not modify the vasoconstrictor responses to phenylephrine.10 Both adrenaline and noradrenaline were more potent hepatic arterial vasoconstrictors after propranolol than in the absence of beta-adrenoceptor blockade. The potentiation of the vasoconstrictor effects of adrenaline was statistically significant.11 After propranolol, adrenaline was a more potent hepatic arterial vasoconstrictor than noradrenaline.12 Since the beta-adrenoceptors in the hepatic arterial vasculature were not blocked by atenolol, but were stimulated by salbutamol, it is concluded that they are predominantly of the beta(2)-type.13 The vasoconstrictor actions of phenylephrine, noradrenaline and adrenaline were all antagonized by the systemic administration of phentolamine, all three dose-response curves being shifted to the right.14 The results are discussed with regard to the possible control of the hepatic arterial vasculature by naturally-occurring catecholamines.", "contents": "The role of beta-adrenoceptors in the responses of the hepatic arterial vascular bed of the dog to phenylephrine, isoprenaline, noradrenaline and adrenaline. 1 The sympathetically-innervated hepatic arterial vascular bed of the dog was perfused from a femoral artery. Hepatic arterial blood flow and perfusion pressure were recorded continuously, and the hepatic arterial vascular resistance (HAVR) calculated from these measurements.2 Intra-arterial injections of phenylephrine caused dose-dependent rises in HAVR, indicating hepatic arterial vasoconstriction, at all doses above threshold. No secondary reductions in HAVR followed these responses.3 Intra-arterial injections of isoprenaline caused only dose-dependent reductions in HAVR at doses above threshold.4 Intra-arterial injections of noradrenaline typically caused an initial increase in HAVR which was followed at all but the highest doses by a secondary, delayed, reduction in HAVR.5 Intra-arterial injections of adrenaline, like those of noradrenaline, resulted in hepatic arterial vasoconstriction followed by hepatic arterial vasodilatation.6 On a molar basis, the most potent hepatic arterial vasoconstrictor was noradrenaline, followed by adrenaline and phenylephrine.7 The maximum reductions in HAVR caused by adrenaline (mean reduction = 21.9%) and noradrenaline (16.9%) were significantly smaller than those due to isoprenaline ((P) < 0.001).8 Propranolol attenuated the hepatic arterial vasodilator responses due to isoprenaline, and the secondary falls in HAVR following intra-arterial adrenaline and noradrenaline.9 Propranolol did not modify the vasoconstrictor responses to phenylephrine.10 Both adrenaline and noradrenaline were more potent hepatic arterial vasoconstrictors after propranolol than in the absence of beta-adrenoceptor blockade. The potentiation of the vasoconstrictor effects of adrenaline was statistically significant.11 After propranolol, adrenaline was a more potent hepatic arterial vasoconstrictor than noradrenaline.12 Since the beta-adrenoceptors in the hepatic arterial vasculature were not blocked by atenolol, but were stimulated by salbutamol, it is concluded that they are predominantly of the beta(2)-type.13 The vasoconstrictor actions of phenylephrine, noradrenaline and adrenaline were all antagonized by the systemic administration of phentolamine, all three dose-response curves being shifted to the right.14 The results are discussed with regard to the possible control of the hepatic arterial vasculature by naturally-occurring catecholamines."}
{"id": "PMID:195665", "title": "Neuroticism and dreaming sleep: a case for interactionism in personality research.", "content": "The value of a trait approach to sleep and dreaming characteristics is evaluated by reviewing recent research on differential patterns and interactions manifest by high and low neuroticism subjects. Differential patterning of dream content and REM sleep characteristics under positive and negative presleep conditions suggest a qualitative difference in experience and behavior, and a quantitative difference in \"importance\" attributable to the dreaming sleep process. It is hypothesized that, under \"normal\" conditions, low neuroticism individuals make more exclusive use of the dreaming period, while under \"artificial\" conditions, they demonstrate a greater motivation to compensate for restricted REM by intensification of the REM process (shortened REM onset latencies, greater REM rebound, intensified dream experiences). Finally, it is suggested that theories of dreaming sleep should recognize the importance of traits, as well as situational factors to the psychology of dreaming sleep.", "contents": "Neuroticism and dreaming sleep: a case for interactionism in personality research. The value of a trait approach to sleep and dreaming characteristics is evaluated by reviewing recent research on differential patterns and interactions manifest by high and low neuroticism subjects. Differential patterning of dream content and REM sleep characteristics under positive and negative presleep conditions suggest a qualitative difference in experience and behavior, and a quantitative difference in \"importance\" attributable to the dreaming sleep process. It is hypothesized that, under \"normal\" conditions, low neuroticism individuals make more exclusive use of the dreaming period, while under \"artificial\" conditions, they demonstrate a greater motivation to compensate for restricted REM by intensification of the REM process (shortened REM onset latencies, greater REM rebound, intensified dream experiences). Finally, it is suggested that theories of dreaming sleep should recognize the importance of traits, as well as situational factors to the psychology of dreaming sleep."}
{"id": "PMID:195666", "title": "Metyrapone in long-term management of Cushing's disease.", "content": "Metyrapone was used in the long-term management of 13 patients with pituitary-dependent bilateral adrenal hyperplasia (Cushing's disease). The total length of treatment ranged from two to 66 months, with a mean of 21 months. The clinical features of the disease rapidly improved on metyrapone and this improvement was maintained. Although plasma ACTH concentrations rose in all patients, the increase was insufficient to overcome the adrenal blockade induced by the drug. Eight of the 13 patients had additional external pituitary irradiation as definitive treatment of their disease and one underwent a transfrontal hypophysectomy. Radiotherapy cured one patient, and after three years metyrapone was withdrawn. Slight hirsuties was noted in four of the seven women who received the drug for six months or more. A fifth woman had more severe hirsuties and this led to bilateral adrenalectomy. Other than hirsuties, side effects were few and the routine use of metyrapone is recommended as an adjunct to more definitive treatment in all patients who present with Cushing's syndrome, irrespective of aetiology.", "contents": "Metyrapone in long-term management of Cushing's disease. Metyrapone was used in the long-term management of 13 patients with pituitary-dependent bilateral adrenal hyperplasia (Cushing's disease). The total length of treatment ranged from two to 66 months, with a mean of 21 months. The clinical features of the disease rapidly improved on metyrapone and this improvement was maintained. Although plasma ACTH concentrations rose in all patients, the increase was insufficient to overcome the adrenal blockade induced by the drug. Eight of the 13 patients had additional external pituitary irradiation as definitive treatment of their disease and one underwent a transfrontal hypophysectomy. Radiotherapy cured one patient, and after three years metyrapone was withdrawn. Slight hirsuties was noted in four of the seven women who received the drug for six months or more. A fifth woman had more severe hirsuties and this led to bilateral adrenalectomy. Other than hirsuties, side effects were few and the routine use of metyrapone is recommended as an adjunct to more definitive treatment in all patients who present with Cushing's syndrome, irrespective of aetiology."}
{"id": "PMID:195667", "title": "BK antibody and virus-specific IgM responses in renal transplant recipients, patients with malignant disease, and healthy people.", "content": "Haemagglutination-inhibition (HAI) antibodies to BK virus, including BK-virus-specific IgM, were determined before and after renal transplantation in 20 patients, in 57 patients with malignant disease, and in 66 healthy controls, Before transplantation 11 of the renal transplant recipients were seronegative, but eight later serocconverted, two before and six after transplantation. Twenty of the patients with malignant disease and 22 controls were also seronegative. The geometric mean titre of BK HAI antibodies was significantly higher among transplanted patients (1/180) than among controls (1/90). BK-virus-specific IgM antibody was detected in seven renal transplant recipients, six patients with malignant disease, and 13 healthy controls. In transplant recipients BK-virus-specific IgM antibody usually persisted throughout the duration of the study, and studies on controls from whom second serum samples were available suggested that they too had persistent BK-virus-specific IgM responses. The geometric mean titre of BK-virus-specific IgM HAI antibody was significantly greater in post-transplantation sera (1/223) than in control sera (1/28). The specificity of the detection of BK-virus-specific IgM HAI antibody was confirmed by direct visualisation of antibody by immune electron microscopy. The persistence of BK-virus-specific IgM suggested that BK virus continued to provide an antigenic stimulus. Nevertheless, there was no obvious association between the serological findings and any clinical features, and prospective studies will be needed to elucidate any such association.", "contents": "BK antibody and virus-specific IgM responses in renal transplant recipients, patients with malignant disease, and healthy people. Haemagglutination-inhibition (HAI) antibodies to BK virus, including BK-virus-specific IgM, were determined before and after renal transplantation in 20 patients, in 57 patients with malignant disease, and in 66 healthy controls, Before transplantation 11 of the renal transplant recipients were seronegative, but eight later serocconverted, two before and six after transplantation. Twenty of the patients with malignant disease and 22 controls were also seronegative. The geometric mean titre of BK HAI antibodies was significantly higher among transplanted patients (1/180) than among controls (1/90). BK-virus-specific IgM antibody was detected in seven renal transplant recipients, six patients with malignant disease, and 13 healthy controls. In transplant recipients BK-virus-specific IgM antibody usually persisted throughout the duration of the study, and studies on controls from whom second serum samples were available suggested that they too had persistent BK-virus-specific IgM responses. The geometric mean titre of BK-virus-specific IgM HAI antibody was significantly greater in post-transplantation sera (1/223) than in control sera (1/28). The specificity of the detection of BK-virus-specific IgM HAI antibody was confirmed by direct visualisation of antibody by immune electron microscopy. The persistence of BK-virus-specific IgM suggested that BK virus continued to provide an antigenic stimulus. Nevertheless, there was no obvious association between the serological findings and any clinical features, and prospective studies will be needed to elucidate any such association."}
{"id": "PMID:195672", "title": "Effects of vagal volleys on units of intralaminar and juxtalaminar thalamic nuclei in monkeys.", "content": "As part of an attempt to clarify the nature of inputs to the limbic cortex, the thalamic intralaminar and juxtalaminar nuclei were explored for unit responses to vagal volleys in awake, sitting squirrel monkeys. Vagal shocks elicited responses of a large percentage of units in the anterior medial, paracentral, lateral dorsal, and lateral, and medial dorsal nuclei, as well as in part of the ventral lateral nucleus adjacent to the paracentral. Responsive units showed either initial excitation or initial inhibition. As in the preceding study on the cingulate and supracingulate cortex, there were two main types of initially excited units: type 1 responded with a discharge of 1-3 spikes at relatively short and constant latencies, while type 2 units were characterized by a burst of 3-14 spikes at longer and more variable latencies. Although the findings were compatible with the hypothesis that the anterior and paracentral nuclei transmit vagal impulses to the cingulate and supracingulate cortex, an analysis of latencies suggested that a more rapidly conducting pathway(s) accounts for latencies as short as 12 msec of some cingulate units. Twenty-eight percent of 367 units in the medial dorsal nucleus responded to vagal volleys. This finding gives substantial support to the traditional view that the medial dorsal nucleus transmits interoceptive information to limbic and neocortical areas of the orbitofrontal region.", "contents": "Effects of vagal volleys on units of intralaminar and juxtalaminar thalamic nuclei in monkeys. As part of an attempt to clarify the nature of inputs to the limbic cortex, the thalamic intralaminar and juxtalaminar nuclei were explored for unit responses to vagal volleys in awake, sitting squirrel monkeys. Vagal shocks elicited responses of a large percentage of units in the anterior medial, paracentral, lateral dorsal, and lateral, and medial dorsal nuclei, as well as in part of the ventral lateral nucleus adjacent to the paracentral. Responsive units showed either initial excitation or initial inhibition. As in the preceding study on the cingulate and supracingulate cortex, there were two main types of initially excited units: type 1 responded with a discharge of 1-3 spikes at relatively short and constant latencies, while type 2 units were characterized by a burst of 3-14 spikes at longer and more variable latencies. Although the findings were compatible with the hypothesis that the anterior and paracentral nuclei transmit vagal impulses to the cingulate and supracingulate cortex, an analysis of latencies suggested that a more rapidly conducting pathway(s) accounts for latencies as short as 12 msec of some cingulate units. Twenty-eight percent of 367 units in the medial dorsal nucleus responded to vagal volleys. This finding gives substantial support to the traditional view that the medial dorsal nucleus transmits interoceptive information to limbic and neocortical areas of the orbitofrontal region."}
{"id": "PMID:195674", "title": "Specific uptake of a behaviorally potent [3H]ACTH4-9 analog in the septal area after intraventricular injection in rats.", "content": "Distribution within the brain of a behaviorally potent [3H]ACTH4-9 analog 2 h after intraventricular injection in rats was studied in the presence and absence of behaviorally and structurally similar peptides, to explore the significance of earlier found preferential uptake of the [3H]ACTH4-9 analog in the septal area. Hypophysectomy resulted in significantly enhanced uptake of radioactivity in the septum as compared to normal rats. No increase in this brain area of hypophysectomized rats was observed after intraventricular injection of [3H]Phe. Elevated circulating ACTH levels after adrenalectomy seemed too low to compete with the septal uptake of the ACTH4-9 analong. Subcutaneous substitution of hypophysectomized rats with sustained release zinc phosphate preparations of the behaviorally equipotent peptides ACTH1-24 and ACTH4-10 decreased the accumulation of the [3H]ACTH4-9 analog in the septum, whereas treatment with the behaviorally inactive fragment ACTH11-24 is not effective. Retreatment of hypophysectomized rats with neuropeptides, differing structurally from natural ACTH peptides (7-D-Phe-ACTH4-10, BETA-LPH61-76 and 9-desglycinamide, 8-Lys-vasopressin), did not change the uptake of the ACTH4-9 analog in any of the investigated brain areas. These results give evidence for specific uptake of the ACTH4-9 analog in the septal region, because competitive displacement occurs only with peptides which both behaviorally and structurally are closely related to the ACTH4-9 analog.", "contents": "Specific uptake of a behaviorally potent [3H]ACTH4-9 analog in the septal area after intraventricular injection in rats. Distribution within the brain of a behaviorally potent [3H]ACTH4-9 analog 2 h after intraventricular injection in rats was studied in the presence and absence of behaviorally and structurally similar peptides, to explore the significance of earlier found preferential uptake of the [3H]ACTH4-9 analog in the septal area. Hypophysectomy resulted in significantly enhanced uptake of radioactivity in the septum as compared to normal rats. No increase in this brain area of hypophysectomized rats was observed after intraventricular injection of [3H]Phe. Elevated circulating ACTH levels after adrenalectomy seemed too low to compete with the septal uptake of the ACTH4-9 analong. Subcutaneous substitution of hypophysectomized rats with sustained release zinc phosphate preparations of the behaviorally equipotent peptides ACTH1-24 and ACTH4-10 decreased the accumulation of the [3H]ACTH4-9 analog in the septum, whereas treatment with the behaviorally inactive fragment ACTH11-24 is not effective. Retreatment of hypophysectomized rats with neuropeptides, differing structurally from natural ACTH peptides (7-D-Phe-ACTH4-10, BETA-LPH61-76 and 9-desglycinamide, 8-Lys-vasopressin), did not change the uptake of the ACTH4-9 analog in any of the investigated brain areas. These results give evidence for specific uptake of the ACTH4-9 analog in the septal region, because competitive displacement occurs only with peptides which both behaviorally and structurally are closely related to the ACTH4-9 analog."}
{"id": "PMID:195675", "title": "Sleep and activity rhythms in mice: a description of circadian patterns and unexpected disruptions in sleep.", "content": "Studies on daily and circadian rhythms in wheel running and electrographically defined wakefulness, NREM sleep, and REM sleep in M. musculus were done to gather data on the temporal distribution of activity and sleep. Generally, peaks in NREM and sleep tended to coincide and to alternate with the coincident peaks of wakefulness and wheel running. However, during the active phase of the circadian wheel running cycle some NREM and REM sleep did occur; conversely, during its rest phase, wakefulness was often present. The most striking finding was that in mice with clearly entrained or free-running activity onsets, the circadian peak-through patterns in wakefulness, NREM, and REM sleep were not always distinct--they could be damped and/or polyphasic. Several explanations of these phenomena are considered.", "contents": "Sleep and activity rhythms in mice: a description of circadian patterns and unexpected disruptions in sleep. Studies on daily and circadian rhythms in wheel running and electrographically defined wakefulness, NREM sleep, and REM sleep in M. musculus were done to gather data on the temporal distribution of activity and sleep. Generally, peaks in NREM and sleep tended to coincide and to alternate with the coincident peaks of wakefulness and wheel running. However, during the active phase of the circadian wheel running cycle some NREM and REM sleep did occur; conversely, during its rest phase, wakefulness was often present. The most striking finding was that in mice with clearly entrained or free-running activity onsets, the circadian peak-through patterns in wakefulness, NREM, and REM sleep were not always distinct--they could be damped and/or polyphasic. Several explanations of these phenomena are considered."}
{"id": "PMID:195676", "title": "ACTH release during passive avoidance behavior.", "content": "ACTH was measured by radioimmunoassay during learning and retention of a passive avoidance response. Electric footshock, used during the learning trial, appeared to be a weaker stimulus for ACTH release than was the retention test. Moreover high latency scores during retention were associated with high plasma ACTH levels, whereas shorter latencies were associated with lower levels. The results indicate that psychological mechanisms organizing behavioral coping are important in the response of the pituitary-adrenocortical system to stimuli which are related to a previous adversive experience.", "contents": "ACTH release during passive avoidance behavior. ACTH was measured by radioimmunoassay during learning and retention of a passive avoidance response. Electric footshock, used during the learning trial, appeared to be a weaker stimulus for ACTH release than was the retention test. Moreover high latency scores during retention were associated with high plasma ACTH levels, whereas shorter latencies were associated with lower levels. The results indicate that psychological mechanisms organizing behavioral coping are important in the response of the pituitary-adrenocortical system to stimuli which are related to a previous adversive experience."}
{"id": "PMID:195681", "title": "The role of carbohydrate in the glycoenzyme invertase of Neurospora crassa.", "content": "Data obtained concerning the carbohydrate moieties of the glycoenzyme invertase (EC 3.2.1.26, beta-D-fructofuranoside fructohydrolase) from Neurospora crassa were consistent with a linkage of some carbohydrate chains by O-glycosidic bonds to serine and threonine residues; the possibility of N-glycosylamine linkage of some of the carbohydrate to the amide group of asparagine is also indicated. The invertase was remarkably stable on storage at low temperatures. Oxidation of the carbohydrate residues in the enzyme by sodium periodate markedly affected the heat-stability of the enzyme. It is suggested that the carbohydrate moieties function as stabilizers of the tertiary structure of the glycoenzyme.", "contents": "The role of carbohydrate in the glycoenzyme invertase of Neurospora crassa. Data obtained concerning the carbohydrate moieties of the glycoenzyme invertase (EC 3.2.1.26, beta-D-fructofuranoside fructohydrolase) from Neurospora crassa were consistent with a linkage of some carbohydrate chains by O-glycosidic bonds to serine and threonine residues; the possibility of N-glycosylamine linkage of some of the carbohydrate to the amide group of asparagine is also indicated. The invertase was remarkably stable on storage at low temperatures. Oxidation of the carbohydrate residues in the enzyme by sodium periodate markedly affected the heat-stability of the enzyme. It is suggested that the carbohydrate moieties function as stabilizers of the tertiary structure of the glycoenzyme."}
{"id": "PMID:195677", "title": "Effect of opiate receptor blockade on pain sensitivity in the rat.", "content": "Blockade of opiate receptors by naloxone (2 mg/kg) was found to produce a significant increase in pain sensitivity as measured by the tail-flick test. This finding supports the view that endogenous opiate systems may play a role in the modulation of pain sensitivity. Naloxone, however, was found to have no effect on pain responsiveness as measured by tail-pinch. These findings, together with additional reports, suggest that endogenous opiate systems may exert differential actions on different sensory modalities.", "contents": "Effect of opiate receptor blockade on pain sensitivity in the rat. Blockade of opiate receptors by naloxone (2 mg/kg) was found to produce a significant increase in pain sensitivity as measured by the tail-flick test. This finding supports the view that endogenous opiate systems may play a role in the modulation of pain sensitivity. Naloxone, however, was found to have no effect on pain responsiveness as measured by tail-pinch. These findings, together with additional reports, suggest that endogenous opiate systems may exert differential actions on different sensory modalities."}
{"id": "PMID:195682", "title": "Effect of lowered intracellular ATP and GTP concentrations on purine ribonucleotide synthesis and interconversion.", "content": "The effects of lowered intracellular ATP and GTP concentrations on enzymes of purine ribonucleotide synthesis and intercoversion were studied using intact Ehrlich ascites tumor cells. The apparent rates of phosphoribosyl pyrophosphate synthetase (EC 2.7.6.1) and of inosinate dehydrogenase (EC 1.2.1.14) were increased in cells containing lowered purine nucleotide concentrations, but apparent activities of amidophosphoribosyltransferase (EC 2.4.2.14), the purine phosphoribosyltransferases, and other enzymes of purine ribonucleotide interconversion were not affected.", "contents": "Effect of lowered intracellular ATP and GTP concentrations on purine ribonucleotide synthesis and interconversion. The effects of lowered intracellular ATP and GTP concentrations on enzymes of purine ribonucleotide synthesis and intercoversion were studied using intact Ehrlich ascites tumor cells. The apparent rates of phosphoribosyl pyrophosphate synthetase (EC 2.7.6.1) and of inosinate dehydrogenase (EC 1.2.1.14) were increased in cells containing lowered purine nucleotide concentrations, but apparent activities of amidophosphoribosyltransferase (EC 2.4.2.14), the purine phosphoribosyltransferases, and other enzymes of purine ribonucleotide interconversion were not affected."}
{"id": "PMID:195683", "title": "Uridine phosphorylase activity of isolated plasma membranes of rat liver.", "content": "Plasma membranes were isolated from rat liver homogenates either by differential centrifugation or by fractionation in discontinuous sucrose density gradients. Both membrane preparations contained about 17% of the total uridine phosphorylase (EC 2.4.2.3) activity and 44% of the total 5'-nucleotidase (EC 3.1.3.5). The enrichment factor for uridine phosphorylase in the fractions prepared by differential centrifugation was about 2.8 and by the gradient method, as much as 11.0; the respective enrichment factors for 5'-nucleotidase were 1.8 and 9.5. Uridine phosphorylase activity of isolated plasma membrane fractions was stimulated 2.5-fold by 0.1% Triton X-100. Unlike the cytosol enzyme, uridine phosphorylase of plasma membranes showed little or no deoxyuridine-cleaving activity. Contamination of the membrane fractions by thymidine phosphorylase (EC 2.4.2.4) of the cytosol was negligible. The other subcellular organelles obtained by either procedure and characterized by marker enzyme activities were found not to contain significant uridine phosphorylase activity; the cytosol fractions contained just over 70% of the total uridine phosphorylase activity with an enrichment of only about 2.8-fold. The activity of the cytosol enzyme was not stimulated by Triton X-100.", "contents": "Uridine phosphorylase activity of isolated plasma membranes of rat liver. Plasma membranes were isolated from rat liver homogenates either by differential centrifugation or by fractionation in discontinuous sucrose density gradients. Both membrane preparations contained about 17% of the total uridine phosphorylase (EC 2.4.2.3) activity and 44% of the total 5'-nucleotidase (EC 3.1.3.5). The enrichment factor for uridine phosphorylase in the fractions prepared by differential centrifugation was about 2.8 and by the gradient method, as much as 11.0; the respective enrichment factors for 5'-nucleotidase were 1.8 and 9.5. Uridine phosphorylase activity of isolated plasma membrane fractions was stimulated 2.5-fold by 0.1% Triton X-100. Unlike the cytosol enzyme, uridine phosphorylase of plasma membranes showed little or no deoxyuridine-cleaving activity. Contamination of the membrane fractions by thymidine phosphorylase (EC 2.4.2.4) of the cytosol was negligible. The other subcellular organelles obtained by either procedure and characterized by marker enzyme activities were found not to contain significant uridine phosphorylase activity; the cytosol fractions contained just over 70% of the total uridine phosphorylase activity with an enrichment of only about 2.8-fold. The activity of the cytosol enzyme was not stimulated by Triton X-100."}
{"id": "PMID:195684", "title": "Correlation between organophosphate poisoning, acetylcholinesterase inhibition, and increased cyclic GMP levels in malathion-treated insects.", "content": "Organophosphate poisoning with malathion caused large increases (up to 125 and 440%, respectively) in the level of cyclic GMP in larvae of Mamestra configurata Wlk. and in the fly Sarcophaga bullata Parker. Cyclic AMP was little affected. The malathion-induced increase in cyclic GMP was time and dose dependent. Time-course studies with the head and thorax of S. bullata demonstrated that the increase in cyclic GMP level occurred precipitously after a lag period  of about 1 h, during which time the activity of acetylcholinesterase (EC 3.1.1.7) was progressively inhibited. The abrupt increase in cyclic GMP began when acetylcholinesterase activity had been inhibited to a sufficient extent to permit accumulation of acetylcholine. It is suggested that the accumulation of acetylcholine in the malathion-poisoned insects caused cyclic GMP levels to rise.  Cyclic GMP may have a role in cholinergic transmission in normally functioning insect neural tissue. Increased levels of cyclic GMP induced by organophosphate and organocholorine (Bodnaryk, R. P. (1976) Can. J. Biochem. 54, 957-962) insecticides appear to be a vital and previously unrecognized biochemical lesion in insects poisoned by these compounds.", "contents": "Correlation between organophosphate poisoning, acetylcholinesterase inhibition, and increased cyclic GMP levels in malathion-treated insects. Organophosphate poisoning with malathion caused large increases (up to 125 and 440%, respectively) in the level of cyclic GMP in larvae of Mamestra configurata Wlk. and in the fly Sarcophaga bullata Parker. Cyclic AMP was little affected. The malathion-induced increase in cyclic GMP was time and dose dependent. Time-course studies with the head and thorax of S. bullata demonstrated that the increase in cyclic GMP level occurred precipitously after a lag period  of about 1 h, during which time the activity of acetylcholinesterase (EC 3.1.1.7) was progressively inhibited. The abrupt increase in cyclic GMP began when acetylcholinesterase activity had been inhibited to a sufficient extent to permit accumulation of acetylcholine. It is suggested that the accumulation of acetylcholine in the malathion-poisoned insects caused cyclic GMP levels to rise.  Cyclic GMP may have a role in cholinergic transmission in normally functioning insect neural tissue. Increased levels of cyclic GMP induced by organophosphate and organocholorine (Bodnaryk, R. P. (1976) Can. J. Biochem. 54, 957-962) insecticides appear to be a vital and previously unrecognized biochemical lesion in insects poisoned by these compounds."}
{"id": "PMID:195685", "title": "The syntheses of alpha-D-glucopyranose-1-phosphates labelled with 18O in the phosphoryl or ester oxygen positions.", "content": "Phosphoryl-oxygen-labelled alpha-D-glucopyranose-1-phosphate (Glc1P) has been prepared by the hydrolysis in 18O-enriched water of alpha-D-glucopyranose-1,2-cyclic phosphate catalyzed by extracts of Saccharomyces fragilis. Ester-oxygen-labelled alpha-D-galactopyranose-1-phosphate has been prepared by galactokinase-(EC 2.7.1.6)-catalyzed phosphorylation of D-[1-18O]-galactose by ATP, and it has been isomerized to ester-oxygen-labelled Glc1P using galactose-1-phosphate uridyltransferase (EC2.7.7.12) and UDPgalactose 4-epimerase (EC 5.1.3.2). These labelled glucose phosphates are for use in oxygen-exchange experiments.", "contents": "The syntheses of alpha-D-glucopyranose-1-phosphates labelled with 18O in the phosphoryl or ester oxygen positions. Phosphoryl-oxygen-labelled alpha-D-glucopyranose-1-phosphate (Glc1P) has been prepared by the hydrolysis in 18O-enriched water of alpha-D-glucopyranose-1,2-cyclic phosphate catalyzed by extracts of Saccharomyces fragilis. Ester-oxygen-labelled alpha-D-galactopyranose-1-phosphate has been prepared by galactokinase-(EC 2.7.1.6)-catalyzed phosphorylation of D-[1-18O]-galactose by ATP, and it has been isomerized to ester-oxygen-labelled Glc1P using galactose-1-phosphate uridyltransferase (EC2.7.7.12) and UDPgalactose 4-epimerase (EC 5.1.3.2). These labelled glucose phosphates are for use in oxygen-exchange experiments."}
{"id": "PMID:195686", "title": "Hypermodified alkali-stable dinucleotide sequences in each of the high-molecular-weight (26S and 18S) ribosomal RNA species of wheat.", "content": "Two hypermodified, alkali-stable dinucleotide sequences, each containing a base modification in addition to sugar methylation, are known to be present in wheat embryo 26S + 18S rRNA (Gray, M.W. (1974) Biochemistry 13, 5453-5463). Quantitative analysis of unfractionated 26S + 18S rRNA had suggested that each of these sequences (Cm-psi p and psi m-Ap, where Cm=O2'-methylcytidine and psi m-O2'-methylpseudouridine) was present in either the 18S or the 26S rRNA species, but not the both, at a frequency of not more than once per chain. In the study reported here, the individual 32P-labeled 18S and 26S rRNA species were isolated from viable wheat embryos germinated in the presence of [32P]orthophosphate. From analyses of phosphodiesterase and alkaline hydrolysates of the separated [32P]RNAs, we conclude that psi m-Ap is confined to wheat cytosol 18S rRNA, whereas Cm-psi p is localized in wheat cytosol 26S rRNA. The presence of psi m in the 18S rRNA of wheat stands in contrast with the situation in animal cells, where this hypermodified nucleoside is located in the 28S rRNA (Khan, M.S.N. & Maden, B.E.H. (1976) J. Mol. Biol. 101, 235-254).", "contents": "Hypermodified alkali-stable dinucleotide sequences in each of the high-molecular-weight (26S and 18S) ribosomal RNA species of wheat. Two hypermodified, alkali-stable dinucleotide sequences, each containing a base modification in addition to sugar methylation, are known to be present in wheat embryo 26S + 18S rRNA (Gray, M.W. (1974) Biochemistry 13, 5453-5463). Quantitative analysis of unfractionated 26S + 18S rRNA had suggested that each of these sequences (Cm-psi p and psi m-Ap, where Cm=O2'-methylcytidine and psi m-O2'-methylpseudouridine) was present in either the 18S or the 26S rRNA species, but not the both, at a frequency of not more than once per chain. In the study reported here, the individual 32P-labeled 18S and 26S rRNA species were isolated from viable wheat embryos germinated in the presence of [32P]orthophosphate. From analyses of phosphodiesterase and alkaline hydrolysates of the separated [32P]RNAs, we conclude that psi m-Ap is confined to wheat cytosol 18S rRNA, whereas Cm-psi p is localized in wheat cytosol 26S rRNA. The presence of psi m in the 18S rRNA of wheat stands in contrast with the situation in animal cells, where this hypermodified nucleoside is located in the 28S rRNA (Khan, M.S.N. & Maden, B.E.H. (1976) J. Mol. Biol. 101, 235-254)."}
{"id": "PMID:195688", "title": "Primary structure and morphine-like activity of human beta-endorphin.", "content": "The complete amino acid sequence of human beta-endorphin was obtained by automatic sequencing of a sulfonyl isothiocyanate derivative of this peptide, in combination with peptide mapping of a tryptic digest of the native molecule. It was found to be identical with the carboxy-terminal portion 61-91 of human beta-lipotropin (beta-LPH). The morphine-like activity of beta-endorphin is comparable both in the mouse vas deferens bioassay and in the opiate receptor binding assay. However, beta-LPH is not active up to concentrations of 10(-6) M.", "contents": "Primary structure and morphine-like activity of human beta-endorphin. The complete amino acid sequence of human beta-endorphin was obtained by automatic sequencing of a sulfonyl isothiocyanate derivative of this peptide, in combination with peptide mapping of a tryptic digest of the native molecule. It was found to be identical with the carboxy-terminal portion 61-91 of human beta-lipotropin (beta-LPH). The morphine-like activity of beta-endorphin is comparable both in the mouse vas deferens bioassay and in the opiate receptor binding assay. However, beta-LPH is not active up to concentrations of 10(-6) M."}
{"id": "PMID:195690", "title": "Effects of antipsychotic drugs on action potential production in skeletal muscle. II. Haloperidol: nonspecific and opiate drug receptor mediated effects.", "content": "The effects of haloperidol, an antipsychotic butyrophenone, on excitability and action potential production in frog's sartorius muscle fibers were studied. This drug produced a local-anestheticlike effect which developed slowly over 1 to 5 h with lower concentrations (2.7 to 5.3 X 10(-6 M) but was completely reversed by exposing the muscles to a drug-free solution. In studies with intracellular microelectrodes, evidence was obtained showing that haloperidol decreased excitability and depressed action potential production by inhibiting the specific increase in sodium conductance (gNa) which normally follows an adequate stimulus. Evidence also was obtained showing an inhibition of the secondary increase in potassium conductance (gK). Haloperidol is structurally related to meperidine and it was found that the inhibition of gNa produced by haloperidol is partially antagonized by low concentrations of naloxone (2.8 X 10(-8) and 2.8 X 10(-7) M); as was previously shown for meperidine. Thus haloperidol, like meperidine, suppresses action potential production by two mechanisms of action: one, a nonspecific local-anaestheticlike effect; and the other, a specific inhibition of gNa mediated by means of an opiate drug receptor associated with the muscle fiber membrane. Naloxone did not antagonize the effects of chlorpromazine on gNa.", "contents": "Effects of antipsychotic drugs on action potential production in skeletal muscle. II. Haloperidol: nonspecific and opiate drug receptor mediated effects. The effects of haloperidol, an antipsychotic butyrophenone, on excitability and action potential production in frog's sartorius muscle fibers were studied. This drug produced a local-anestheticlike effect which developed slowly over 1 to 5 h with lower concentrations (2.7 to 5.3 X 10(-6 M) but was completely reversed by exposing the muscles to a drug-free solution. In studies with intracellular microelectrodes, evidence was obtained showing that haloperidol decreased excitability and depressed action potential production by inhibiting the specific increase in sodium conductance (gNa) which normally follows an adequate stimulus. Evidence also was obtained showing an inhibition of the secondary increase in potassium conductance (gK). Haloperidol is structurally related to meperidine and it was found that the inhibition of gNa produced by haloperidol is partially antagonized by low concentrations of naloxone (2.8 X 10(-8) and 2.8 X 10(-7) M); as was previously shown for meperidine. Thus haloperidol, like meperidine, suppresses action potential production by two mechanisms of action: one, a nonspecific local-anaestheticlike effect; and the other, a specific inhibition of gNa mediated by means of an opiate drug receptor associated with the muscle fiber membrane. Naloxone did not antagonize the effects of chlorpromazine on gNa."}
{"id": "PMID:195691", "title": "Sequential changes in hepatic polyamine, deoxyribonucleic acid, and cyclic adenosine 3',5'-monophosphate metabolism after subacute exposure to cadmium in rats.", "content": "Heavy metal treatment (2 X 1 mg/kg per day) for 3, 5, and 7 days resulted in progressive augmentation in the incorporation of [14C]thymidine into hepatic DNA. In contrast with the observed enhancement in DNA synthesis, cadmium exposure tended to produce a decrease in the activity of hepatic ornithine decarboxylase (EC 4.1.1.17) at 1, 3, or 5 days with the lowest (34% of control values) enzymic activity seen after 7 days. A similar reduction in the activity of S-adenosylmethionine decarboxylase (EC 4.1.1.50) was observed in livers of rats treated with cadmium for 1-7 days. Subacute exposure to cadmium significantly lowered the hepatic levels of spermidine and spermine whereas the endogenous concentrated of putrescine remained unaltered. In addition to the observed effects on the biosynthesis of polyamines and DNA, heavy metal treatment produced stimulation of the hepatic adenylate cyclase (EC 4.6.1.1)--cyclic AMP system. Significant increases in the activity of hepatic adenylate cyclase and endogenous cyclic AMP levels were detected as early as 1 day and the observed alterations persisted during the entire 1-week period of cadmium exposure. The depression in polyamine formation was accompanied by enhanced DNA biosynthesis as well as stimulation in the adenylate cyclase-cyclic AMP system of rat liver.", "contents": "Sequential changes in hepatic polyamine, deoxyribonucleic acid, and cyclic adenosine 3',5'-monophosphate metabolism after subacute exposure to cadmium in rats. Heavy metal treatment (2 X 1 mg/kg per day) for 3, 5, and 7 days resulted in progressive augmentation in the incorporation of [14C]thymidine into hepatic DNA. In contrast with the observed enhancement in DNA synthesis, cadmium exposure tended to produce a decrease in the activity of hepatic ornithine decarboxylase (EC 4.1.1.17) at 1, 3, or 5 days with the lowest (34% of control values) enzymic activity seen after 7 days. A similar reduction in the activity of S-adenosylmethionine decarboxylase (EC 4.1.1.50) was observed in livers of rats treated with cadmium for 1-7 days. Subacute exposure to cadmium significantly lowered the hepatic levels of spermidine and spermine whereas the endogenous concentrated of putrescine remained unaltered. In addition to the observed effects on the biosynthesis of polyamines and DNA, heavy metal treatment produced stimulation of the hepatic adenylate cyclase (EC 4.6.1.1)--cyclic AMP system. Significant increases in the activity of hepatic adenylate cyclase and endogenous cyclic AMP levels were detected as early as 1 day and the observed alterations persisted during the entire 1-week period of cadmium exposure. The depression in polyamine formation was accompanied by enhanced DNA biosynthesis as well as stimulation in the adenylate cyclase-cyclic AMP system of rat liver."}
{"id": "PMID:195692", "title": "Action of a beta-bungarotoxin on autonomic ganglia and adrenergic neurotransmission.", "content": "A beta-bungarotoxin was isolated from the venom of Bungarus multicinctus by column chromatography on Sephadex G-50 and SP-Sephadex. The toxin produced presynaptic effects on neuromuscular transmission with characteristics similar to those described by others. In a sympathetic ganglion, the toxin increased spontaneous acetylcholine (ACh) release and decreased ACh release evoked by preganglionic nerve stimulation. The toxin did not block the response of isolated ileum to cholinergic nerve stimulation, did not block the release of noradrenaline from the adrenergic nerve terminals of a nictitating membrane preparation, and did not alter the responses of smooth and cardiac muscle preparations to noradrenaline. It is suggested that the specificity of beta-bungarotoxin for certain nerve terminals is related either to selective binding of the toxin or to the selective presence of a necessary substrate for its action. An attempt to show selective binding of 125I-toxin to cholinergic nerve terminals in skeletal muscle was not successful.", "contents": "Action of a beta-bungarotoxin on autonomic ganglia and adrenergic neurotransmission. A beta-bungarotoxin was isolated from the venom of Bungarus multicinctus by column chromatography on Sephadex G-50 and SP-Sephadex. The toxin produced presynaptic effects on neuromuscular transmission with characteristics similar to those described by others. In a sympathetic ganglion, the toxin increased spontaneous acetylcholine (ACh) release and decreased ACh release evoked by preganglionic nerve stimulation. The toxin did not block the response of isolated ileum to cholinergic nerve stimulation, did not block the release of noradrenaline from the adrenergic nerve terminals of a nictitating membrane preparation, and did not alter the responses of smooth and cardiac muscle preparations to noradrenaline. It is suggested that the specificity of beta-bungarotoxin for certain nerve terminals is related either to selective binding of the toxin or to the selective presence of a necessary substrate for its action. An attempt to show selective binding of 125I-toxin to cholinergic nerve terminals in skeletal muscle was not successful."}
{"id": "PMID:195693", "title": "Biochemical reactions involved in pancreatic enzyme secretion. 4. Effects of cytochalasin B on functions of the exocrine pancreas.", "content": "These experiments were performed to evaluate the effects of cytochalasin B on pancreatic enzyme secretion and thus perhaps establish a role for microfilaments in the exocytosis process. The alkaloid at a concentration of 1 microgram/ml (2micron) inhibits amylase secretion induced by urecholine or cholecystokinin-pancreozymin (CCK-PZ) but does not modify that induced by dibutyryl cyclic AMP. The inhibitory effect of the drug is reversible after a 30-min washing out period. It does not affect O2 consumption, basal calcium efflux, or efflux caused by CCK-PZ. Amino acid accumulation in the tissue and their incorporation into proteins are not modified. It is suggested that cytochalasin B inhibits pancreatic enzyme secretion, probably through an effect on the microfilament system.", "contents": "Biochemical reactions involved in pancreatic enzyme secretion. 4. Effects of cytochalasin B on functions of the exocrine pancreas. These experiments were performed to evaluate the effects of cytochalasin B on pancreatic enzyme secretion and thus perhaps establish a role for microfilaments in the exocytosis process. The alkaloid at a concentration of 1 microgram/ml (2micron) inhibits amylase secretion induced by urecholine or cholecystokinin-pancreozymin (CCK-PZ) but does not modify that induced by dibutyryl cyclic AMP. The inhibitory effect of the drug is reversible after a 30-min washing out period. It does not affect O2 consumption, basal calcium efflux, or efflux caused by CCK-PZ. Amino acid accumulation in the tissue and their incorporation into proteins are not modified. It is suggested that cytochalasin B inhibits pancreatic enzyme secretion, probably through an effect on the microfilament system."}
{"id": "PMID:195694", "title": "Angiotensinase activity and angiotensin receptor binding in guinea pig aorta.", "content": "The angiotensinase (EC 3.4.99.3) activity of the subcellular fractions of guinea pig aorta has been studied in relation to their [14C]angiotensin binding capacity. The enzyme activity occurs in the following decreasing order: supernatant greater than plasma membrane fraction greater than 105 000 X g pellet greater than mitochondrial fraction. The specific binding of [14C]angiotensin to these fractions follows the same pattern. Pretreatment of the subcellular fractions at 47 degrees C for 20 min was performed in an attempt to differentiate binding of angiotensin to the pharmacological receptor from binding to the destroying enzymes. This procedure decreased the angiotensinase activity in the plasma membrane fraction only whereas the specific binding of [14C]angiotensin to this fraction was not significantly decreased, suggesting that the plasma membrane angiotensinase is a thermolabile enzyme.", "contents": "Angiotensinase activity and angiotensin receptor binding in guinea pig aorta. The angiotensinase (EC 3.4.99.3) activity of the subcellular fractions of guinea pig aorta has been studied in relation to their [14C]angiotensin binding capacity. The enzyme activity occurs in the following decreasing order: supernatant greater than plasma membrane fraction greater than 105 000 X g pellet greater than mitochondrial fraction. The specific binding of [14C]angiotensin to these fractions follows the same pattern. Pretreatment of the subcellular fractions at 47 degrees C for 20 min was performed in an attempt to differentiate binding of angiotensin to the pharmacological receptor from binding to the destroying enzymes. This procedure decreased the angiotensinase activity in the plasma membrane fraction only whereas the specific binding of [14C]angiotensin to this fraction was not significantly decreased, suggesting that the plasma membrane angiotensinase is a thermolabile enzyme."}
{"id": "PMID:195695", "title": "Urinary cyclic AMP excretion during volume expansion in the rat.", "content": "We have studied the effect of volume expansion with 0.9% saline solution (10% body weight in 1 h) on urinary cyclic AMP excretion in rats. In nine normal rats urinary cyclic AMP excretion (picomoles/minute) was 113.9+/-9.9 during the control period, rose significantly to 171+/-20 during the first 10 min of expansion, came back to control levels for the next 20 min, and finally decreased significantly to 48.8+/-13.2 at the end of the expansion period. In nine parathyroidectomized rats control cyclic AMP excretion was 78.0+/-4.5, did not rise during expansion, and decreased significantly (to 33.7+/-4.1) at the end of the expansion period. The transient increase in cyclic AMP excretion observed in normal rats could be due to parathyroid hormone release. Our studies do not allow us to explain the subsequent decrease noted in both groups.", "contents": "Urinary cyclic AMP excretion during volume expansion in the rat. We have studied the effect of volume expansion with 0.9% saline solution (10% body weight in 1 h) on urinary cyclic AMP excretion in rats. In nine normal rats urinary cyclic AMP excretion (picomoles/minute) was 113.9+/-9.9 during the control period, rose significantly to 171+/-20 during the first 10 min of expansion, came back to control levels for the next 20 min, and finally decreased significantly to 48.8+/-13.2 at the end of the expansion period. In nine parathyroidectomized rats control cyclic AMP excretion was 78.0+/-4.5, did not rise during expansion, and decreased significantly (to 33.7+/-4.1) at the end of the expansion period. The transient increase in cyclic AMP excretion observed in normal rats could be due to parathyroid hormone release. Our studies do not allow us to explain the subsequent decrease noted in both groups."}
{"id": "PMID:195696", "title": "Dopamine beta-hydroxylase and cytochrome oxidase activities in brown adipose tissue of newborn rats following sympathectomy with 6-hydroxydopamine.", "content": "Dopamine-beta-hydroxylase (DBH) (EC 1.14.17.1) activity is present in the interscapular brown adipose tissue (IBAT) as early as 2 days of age in the white rat. The specific and the total activities of this enzyme, as well as those of cytochrome oxidase (COX) (EC 1.9.3.1) in IBAT increase up to at least 20 days of age. Daily administration of 6-hydroxydopamine (6-OHDA) between the second and the twelfth day after birth does not significantly alter IBAT weight gain relative to untreated controls, but the increase in protein content with age is reduced to about half the normal value at the end of the treatment. The treatment with 6-OHDA also results in a drastic lowering of DBH specific and total activities, and a much smaller rate of increase of COX specific and total activities with age in IBAT compared with controls. These results provide additional evidence for a previously proposed role of sympathetic nervous system activity in the development of the thermogenic potential of IBAT in the newborn rat.", "contents": "Dopamine beta-hydroxylase and cytochrome oxidase activities in brown adipose tissue of newborn rats following sympathectomy with 6-hydroxydopamine. Dopamine-beta-hydroxylase (DBH) (EC 1.14.17.1) activity is present in the interscapular brown adipose tissue (IBAT) as early as 2 days of age in the white rat. The specific and the total activities of this enzyme, as well as those of cytochrome oxidase (COX) (EC 1.9.3.1) in IBAT increase up to at least 20 days of age. Daily administration of 6-hydroxydopamine (6-OHDA) between the second and the twelfth day after birth does not significantly alter IBAT weight gain relative to untreated controls, but the increase in protein content with age is reduced to about half the normal value at the end of the treatment. The treatment with 6-OHDA also results in a drastic lowering of DBH specific and total activities, and a much smaller rate of increase of COX specific and total activities with age in IBAT compared with controls. These results provide additional evidence for a previously proposed role of sympathetic nervous system activity in the development of the thermogenic potential of IBAT in the newborn rat."}
{"id": "PMID:195698", "title": "ICMSF methods studies. VIII. Comparative study for the enumeration of Clostridium perfringens in foods.", "content": "Four methods were compared in an international comparative study for the enumeration of Clostridium perfringens: the SFP (Shahidi-Ferguson perfringens) agar (A), TSC (tryptose-sulfite-cycloserin) agar (B), SC (sulfite-cycloserine) agar (C), and neomycin blood agar (D) methods. The confirmed C. perfringens counts were slightly lower for D than for A-C. The percentages of presumptive colonies confirmed as C. perfringens were essentially the same in each method. The relative numbers of nonspecific colonies were the lowest in C, followed by B, D, and A. The methods were also compared for simplicity and for aspects associated with the recognition and selection of presumptive colonies.", "contents": "ICMSF methods studies. VIII. Comparative study for the enumeration of Clostridium perfringens in foods. Four methods were compared in an international comparative study for the enumeration of Clostridium perfringens: the SFP (Shahidi-Ferguson perfringens) agar (A), TSC (tryptose-sulfite-cycloserin) agar (B), SC (sulfite-cycloserine) agar (C), and neomycin blood agar (D) methods. The confirmed C. perfringens counts were slightly lower for D than for A-C. The percentages of presumptive colonies confirmed as C. perfringens were essentially the same in each method. The relative numbers of nonspecific colonies were the lowest in C, followed by B, D, and A. The methods were also compared for simplicity and for aspects associated with the recognition and selection of presumptive colonies."}
{"id": "PMID:195699", "title": "Nitrous oxide as end product of denitrification by strains of fluorescent pseudomonads.", "content": "Growing cultures of several strains of Pseudomonas fluorescens and Pseudomonas chlororaphis produced N2O as the only detectable gaseous product of denitrification, and other strains produced N2 as the gaseous end product of denitrification. All of the nitrogen in NO3- or NO2- added to cell suspensions of the N2O-producing strains P. fluorescens PJ 185 and P. chlororaphis B-560 was recovered as N2O. All of the nitrogen in NO3- or NO2- added to cell suspensions of the N2-producing strain P. fluorescens PJ70 was converted to N2. Cell extracts of P. fluorescens PJ 70, PJ 185, and P. chlororaphis B-560 exhibited NO3- reductase activity when sodium succinate was the electron donor. Reduced nicotinamide adenine dinucleotide and flavine adenine dinucleotide were required to demonstrate NO2- reductase activity in cell extracts.", "contents": "Nitrous oxide as end product of denitrification by strains of fluorescent pseudomonads. Growing cultures of several strains of Pseudomonas fluorescens and Pseudomonas chlororaphis produced N2O as the only detectable gaseous product of denitrification, and other strains produced N2 as the gaseous end product of denitrification. All of the nitrogen in NO3- or NO2- added to cell suspensions of the N2O-producing strains P. fluorescens PJ 185 and P. chlororaphis B-560 was recovered as N2O. All of the nitrogen in NO3- or NO2- added to cell suspensions of the N2-producing strain P. fluorescens PJ70 was converted to N2. Cell extracts of P. fluorescens PJ 70, PJ 185, and P. chlororaphis B-560 exhibited NO3- reductase activity when sodium succinate was the electron donor. Reduced nicotinamide adenine dinucleotide and flavine adenine dinucleotide were required to demonstrate NO2- reductase activity in cell extracts."}
{"id": "PMID:195700", "title": "Enterotoxin formation by Clostridium perfringens type A studied by the use of fluorescent antibody.", "content": "Fluorescein isothiocyanate-conjugated antibody to purified enterotoxin of Clostridium perfringens was used to study the intracellular formation of enterotoxin by this organism. Enterotoxin was detected at 4 h of growth at the end of the cell containing forespore. With the development of the spore, enterotoxin accumulation continued and involved the entire length of the cell until its lysis with the release of enterotoxin and mature spore. The spores did not contain demonstrable enterotoxin. Only a certain number of the sporulated cells of the enterotoxigenic strains studied produced this toxin. The amount of enterotoxin produced varied with sporulation percentage, and between strains and individual cells.", "contents": "Enterotoxin formation by Clostridium perfringens type A studied by the use of fluorescent antibody. Fluorescein isothiocyanate-conjugated antibody to purified enterotoxin of Clostridium perfringens was used to study the intracellular formation of enterotoxin by this organism. Enterotoxin was detected at 4 h of growth at the end of the cell containing forespore. With the development of the spore, enterotoxin accumulation continued and involved the entire length of the cell until its lysis with the release of enterotoxin and mature spore. The spores did not contain demonstrable enterotoxin. Only a certain number of the sporulated cells of the enterotoxigenic strains studied produced this toxin. The amount of enterotoxin produced varied with sporulation percentage, and between strains and individual cells."}
{"id": "PMID:195701", "title": "Malignant parotid tumors: natural history and treatment.", "content": "Sixty-seven cases of histologically proven malignant parotid tumors are presented. Forty percent of the tumors were differentiated adenocarcinoma, while malignant mixed tumors (or pleomorphic adenocarcinomas) formed 18%. The remaining types of malignant salivary tumors are also represented in the series. The natural history and spread of these tumors are studied in detail, with lymph-node metastasis occurring in 25% of the cases and distant metastasis in 20%. Malignant tumors involve largely the retromandibular portion of the parotid gland in over 40% of the cases and the preauricular portion in about one-fifth of the cases. Both regions are affected in a further fifth of the cases. A combination of surgery and radiotherapy was the method employed for curative therapy, with radiotherapy alone reserved mainly for palliation. While the overall five-year survival was 42%, late recurrences constitute a serious problem with eventual demise of about half of these patients. Various factors affecting the prognosis, including histological type of tumor, method of treatment and response to radiotherapy are discussed.", "contents": "Malignant parotid tumors: natural history and treatment. Sixty-seven cases of histologically proven malignant parotid tumors are presented. Forty percent of the tumors were differentiated adenocarcinoma, while malignant mixed tumors (or pleomorphic adenocarcinomas) formed 18%. The remaining types of malignant salivary tumors are also represented in the series. The natural history and spread of these tumors are studied in detail, with lymph-node metastasis occurring in 25% of the cases and distant metastasis in 20%. Malignant tumors involve largely the retromandibular portion of the parotid gland in over 40% of the cases and the preauricular portion in about one-fifth of the cases. Both regions are affected in a further fifth of the cases. A combination of surgery and radiotherapy was the method employed for curative therapy, with radiotherapy alone reserved mainly for palliation. While the overall five-year survival was 42%, late recurrences constitute a serious problem with eventual demise of about half of these patients. Various factors affecting the prognosis, including histological type of tumor, method of treatment and response to radiotherapy are discussed."}
{"id": "PMID:195702", "title": "Radiation-induced cranial nerve palsy.", "content": "Twenty-five patients with 35 cranial nerve palsies were seen at the Fondation Curie during follow-up after radical radiotherapy for head and neck tumors. The twelfth nerve was involved in 19 cases, the tenth in nine, and the eleventh in five; the fifth and second nerves were involved once each and in the same patient. The twelfth nerve was involved alone in 16 patients and the tenth nerve alone in three, with multiple nerves involved in the remaining six patients. The palsy was noted from 12 to 145 months after diagnosis of the tumor. The latency period could be correlated with dose so that the least square fit equation representing NSD vs delay in NSD = 2598 - Delay (in months) X 4.6, with a correlation coefficient of -0.58. The distinction between tumor recurrence and radiation-induced nerve palsy is critical. It can often be inferred from the latency period but must be confirmed by observation over a period of time.", "contents": "Radiation-induced cranial nerve palsy. Twenty-five patients with 35 cranial nerve palsies were seen at the Fondation Curie during follow-up after radical radiotherapy for head and neck tumors. The twelfth nerve was involved in 19 cases, the tenth in nine, and the eleventh in five; the fifth and second nerves were involved once each and in the same patient. The twelfth nerve was involved alone in 16 patients and the tenth nerve alone in three, with multiple nerves involved in the remaining six patients. The palsy was noted from 12 to 145 months after diagnosis of the tumor. The latency period could be correlated with dose so that the least square fit equation representing NSD vs delay in NSD = 2598 - Delay (in months) X 4.6, with a correlation coefficient of -0.58. The distinction between tumor recurrence and radiation-induced nerve palsy is critical. It can often be inferred from the latency period but must be confirmed by observation over a period of time."}
{"id": "PMID:195703", "title": "Lipid cell tumor of the ovary: an ultrastructural study.", "content": "An ovarian lipid cell tumor without Reinke's crystalloids in a woman with secondary amenorrhea, minimal hirsutism, and elevated 17-ketosteroid excretion was studied by light and electron microscopy. Tumor cells were found in small clumps or scattered singly within a collagenous matrix. The cytoplasm of the tumor cells contained abundant smooth endoplasmic reticula, numerous mitochondria with tubular cristae, lipid droplets, lysosomal dense bodies, and concentric membranous whorls, characteristic of steroidogenic cells. In addition, \"peripheral canalicular systems\" were found at the outer margins of the nests of the tumor cells. These \"peripheral canalicular systems\" were bordered by the cell membranes and the surrounding collagenous stroma into which microvilli projected. Since the intercellular canalicular system present between the tumor cells was continuous with the \"peripheral canalicular system,\" both systems probably have a common function related to steroid metabolism. The intercellular and \"peripheral\" canalicular systems and cytoplasmic microfilaments found in this tumor suggest that this ovarian lipid cell tumor was derived from the ovarian stroma.", "contents": "Lipid cell tumor of the ovary: an ultrastructural study. An ovarian lipid cell tumor without Reinke's crystalloids in a woman with secondary amenorrhea, minimal hirsutism, and elevated 17-ketosteroid excretion was studied by light and electron microscopy. Tumor cells were found in small clumps or scattered singly within a collagenous matrix. The cytoplasm of the tumor cells contained abundant smooth endoplasmic reticula, numerous mitochondria with tubular cristae, lipid droplets, lysosomal dense bodies, and concentric membranous whorls, characteristic of steroidogenic cells. In addition, \"peripheral canalicular systems\" were found at the outer margins of the nests of the tumor cells. These \"peripheral canalicular systems\" were bordered by the cell membranes and the surrounding collagenous stroma into which microvilli projected. Since the intercellular canalicular system present between the tumor cells was continuous with the \"peripheral canalicular system,\" both systems probably have a common function related to steroid metabolism. The intercellular and \"peripheral\" canalicular systems and cytoplasmic microfilaments found in this tumor suggest that this ovarian lipid cell tumor was derived from the ovarian stroma."}
{"id": "PMID:195704", "title": "Malignant giant cell tumor of soft parts. An ultrastructural study of four cases.", "content": "Four cases of malignant giant cell tumor of soft parts (MGCT) were studied ultrastructurally. Most of the cells in three cases were identified as undifferentiated mesenchymal cells and mononuclear monohistiocytic cells. The osteoclastlike cells seemed to arise from fusion of monohistiocytic cells. Immature fibroblastic cells, occasionally containing filaments with densities, were also present. They were scarce in three cases and predominant in the fourth. It was concluded that MGCT is a mesenchymal sarcoma with a bimorphic--monohistiocytic and fibroblastic--differentiation. MGCT is therefore considered a special variant of malignant fibrous histiocytoma.", "contents": "Malignant giant cell tumor of soft parts. An ultrastructural study of four cases. Four cases of malignant giant cell tumor of soft parts (MGCT) were studied ultrastructurally. Most of the cells in three cases were identified as undifferentiated mesenchymal cells and mononuclear monohistiocytic cells. The osteoclastlike cells seemed to arise from fusion of monohistiocytic cells. Immature fibroblastic cells, occasionally containing filaments with densities, were also present. They were scarce in three cases and predominant in the fourth. It was concluded that MGCT is a mesenchymal sarcoma with a bimorphic--monohistiocytic and fibroblastic--differentiation. MGCT is therefore considered a special variant of malignant fibrous histiocytoma."}
{"id": "PMID:195705", "title": "Malignant fibrous histiocytoma. An electron microscopic study.", "content": "Sixteen cases of malignant fibrous histiocytoma are presented. Electron microscopy of 15 cases demonstrated fibroblast-like and mononuclear and multinucleated histiocyte-like cells. A small capillary was at the center of all storiform areas examined. Ultrastructural examination can be diagnostically useful within the context of a narrow differential diagnosis by conventional microscopy and the ability, by electron microscopy, to eliminate other mesenchymal cell types. In 13 cases, follow-up information was available from 18 months to 9 years following histological diagnosis. Five patients are alive and 8 patients have died, including two non-tumor related deaths. In 3 cases follow-up was less than 4 months. The biologic behavior of the tumor in this series was generally not related to histopathological parameters. The issue of histogenesis is largely unresolvable. Ultrastructural studies of various types of fibrous histiocytomas, suggesting cells of origin other than histiocytes, give credence to the concept that the histiocyte may represent a morphologic state of a given mesenchymal cell rather than a particular cell type.", "contents": "Malignant fibrous histiocytoma. An electron microscopic study. Sixteen cases of malignant fibrous histiocytoma are presented. Electron microscopy of 15 cases demonstrated fibroblast-like and mononuclear and multinucleated histiocyte-like cells. A small capillary was at the center of all storiform areas examined. Ultrastructural examination can be diagnostically useful within the context of a narrow differential diagnosis by conventional microscopy and the ability, by electron microscopy, to eliminate other mesenchymal cell types. In 13 cases, follow-up information was available from 18 months to 9 years following histological diagnosis. Five patients are alive and 8 patients have died, including two non-tumor related deaths. In 3 cases follow-up was less than 4 months. The biologic behavior of the tumor in this series was generally not related to histopathological parameters. The issue of histogenesis is largely unresolvable. Ultrastructural studies of various types of fibrous histiocytomas, suggesting cells of origin other than histiocytes, give credence to the concept that the histiocyte may represent a morphologic state of a given mesenchymal cell rather than a particular cell type."}
{"id": "PMID:195706", "title": "A new histochemical approach to olfactory esthesioneuroma. A nasal tumor of neural crest origin.", "content": "A close collaboration between E.N.T. surgeons and pathologists permitted us to obtain 6 cases of olfactory esthesioneuroma in which fresh tumor tissue was available. Histochemical and biochemical studies were made in comparison with neuroblastoma. Different reactions and assays performed revealed a similarity with sympathetic tumors. Moreover, the presence of catecholamines in esthesioneuroma provides a great help in diagnostic as does electron microscope examination.", "contents": "A new histochemical approach to olfactory esthesioneuroma. A nasal tumor of neural crest origin. A close collaboration between E.N.T. surgeons and pathologists permitted us to obtain 6 cases of olfactory esthesioneuroma in which fresh tumor tissue was available. Histochemical and biochemical studies were made in comparison with neuroblastoma. Different reactions and assays performed revealed a similarity with sympathetic tumors. Moreover, the presence of catecholamines in esthesioneuroma provides a great help in diagnostic as does electron microscope examination."}
{"id": "PMID:195707", "title": "Serum glutamic oxalacetic transaminase/glutamic pyruvic transaminase ratios in hepatocellular carcinoma.", "content": "Serum enzyme activities were studied in 131 cases of hepatocellular carcinoma (HCC), 76 cases of metastatic liver carcinomas (MLC) and 234 cases of hepatic cirrhosis. SGOT was elevated above SGPT in most of the time in these patients, SGOT/SGPT was greater in HCC compared with other groups, and that this ratio increased during the preterminal period more markedly in patients with HCC because of the significant increase of SGOT in the face of relatively stable SGPT. Preterminal rises of alkaline phosphatase and LDH activities were more pronounced in MLC. Leucine aminopeptidase activity exhibited no characteristic feature of diagnostic value. Of the five enzymes, SGOT changes were more closely correlated with the growth of HCC; SGPT reflected more of the liver parenchymal damage while SGOT was probably accounted for in part by tumor-derived GOT. Other clinical and pathological implications are discussed.", "contents": "Serum glutamic oxalacetic transaminase/glutamic pyruvic transaminase ratios in hepatocellular carcinoma. Serum enzyme activities were studied in 131 cases of hepatocellular carcinoma (HCC), 76 cases of metastatic liver carcinomas (MLC) and 234 cases of hepatic cirrhosis. SGOT was elevated above SGPT in most of the time in these patients, SGOT/SGPT was greater in HCC compared with other groups, and that this ratio increased during the preterminal period more markedly in patients with HCC because of the significant increase of SGOT in the face of relatively stable SGPT. Preterminal rises of alkaline phosphatase and LDH activities were more pronounced in MLC. Leucine aminopeptidase activity exhibited no characteristic feature of diagnostic value. Of the five enzymes, SGOT changes were more closely correlated with the growth of HCC; SGPT reflected more of the liver parenchymal damage while SGOT was probably accounted for in part by tumor-derived GOT. Other clinical and pathological implications are discussed."}
{"id": "PMID:195708", "title": "Cellular immunity to herpes simplex virus in man. VII. K-cell activity to HSV1 infected target cells in disease.", "content": "Herpes simplex virus-infected target cells, sensitised with antiviral antibody can be lysed by non-immune human lymphocytes (K-cells). This antibody dependent cell mediated immunity (ADCC) is a very efficient technique for destroying foreign target cells and may play a role in maintaining the localization of recurrent herpetic infections. We have used 51Cr labelled herpes virus infected target cells to examine the K-cell activity of peripheral blood lymphocytes in patients who have either malignant reticuloendothelial diseases or who are receiving cytotoxic and steroid therapy for other reasons. K-cell activity was generally within the normal range in such patients and was surprisingly stable despite the occasional use of relatively large doses of cytotoxic agents. It is unlikely, therefore, that a defect in ADCC is responsible for the dissemination of herpes virus infections that may be seen in association with the above drugs and diseases.", "contents": "Cellular immunity to herpes simplex virus in man. VII. K-cell activity to HSV1 infected target cells in disease. Herpes simplex virus-infected target cells, sensitised with antiviral antibody can be lysed by non-immune human lymphocytes (K-cells). This antibody dependent cell mediated immunity (ADCC) is a very efficient technique for destroying foreign target cells and may play a role in maintaining the localization of recurrent herpetic infections. We have used 51Cr labelled herpes virus infected target cells to examine the K-cell activity of peripheral blood lymphocytes in patients who have either malignant reticuloendothelial diseases or who are receiving cytotoxic and steroid therapy for other reasons. K-cell activity was generally within the normal range in such patients and was surprisingly stable despite the occasional use of relatively large doses of cytotoxic agents. It is unlikely, therefore, that a defect in ADCC is responsible for the dissemination of herpes virus infections that may be seen in association with the above drugs and diseases."}
{"id": "PMID:195709", "title": "Clinical report of the treatment of locally advanced lung cancer.", "content": "This paper discusses the results of the treatment of 345 patients entered in the Veterans Administration Lung Group Protocol 13L. The study was activated March 1972, and closed for the patient accesion March 1975. All patients had a histological diagnosis of primary lung cancer considered clinically non-resectable or inoperable. Patients were equally randomized into two groups, radiotherapy alone or radiotherapy with chemotherapy. The analysis of the data included: treatment regimen, radiation dose, initial performance status, performance status change, cell type, duration of survival, quality of survival and age. The strongest influence on median survival was the level of radiation dose. The small cell carcinoma patients treated with radiotherapy and chemotherapy showed significant improvement in the median survival (38.2 weeks) over the patients treated with radiotherapy alone (20.6 weeks). The patients treated with radiotherapy and chemotherapy also showed improvement in performance status more frequently than the patients treated with radiotherapy alone. Other parameters of the analysis will be presented.", "contents": "Clinical report of the treatment of locally advanced lung cancer. This paper discusses the results of the treatment of 345 patients entered in the Veterans Administration Lung Group Protocol 13L. The study was activated March 1972, and closed for the patient accesion March 1975. All patients had a histological diagnosis of primary lung cancer considered clinically non-resectable or inoperable. Patients were equally randomized into two groups, radiotherapy alone or radiotherapy with chemotherapy. The analysis of the data included: treatment regimen, radiation dose, initial performance status, performance status change, cell type, duration of survival, quality of survival and age. The strongest influence on median survival was the level of radiation dose. The small cell carcinoma patients treated with radiotherapy and chemotherapy showed significant improvement in the median survival (38.2 weeks) over the patients treated with radiotherapy alone (20.6 weeks). The patients treated with radiotherapy and chemotherapy also showed improvement in performance status more frequently than the patients treated with radiotherapy alone. Other parameters of the analysis will be presented."}
{"id": "PMID:195710", "title": "The viral etiology of cancer: a realistic approach.", "content": "The etiology of cancer resembles that of many other diseases in that multiple factors may be required. Because of this, the role or viruses in the etiology of human cancers is especially difficult to assess. When animal tumor systems were used as models, the roles of various predisposing characteristics in virus oncogenesis were elucidated. Extrapolation of these findings to the human diseases suggests the importance of genetics, age, hormones, immune competence, and stress in determining susceptibility to tumor development in individuals infected with an oncogenic virus. The importance of cofactors in induction of those human tumors most strongly associated with virus infection, including Burkitt's lymphoma, nasopharyngeal carcinoma, cerviccal carcinoma, acute myelogenous leukemia, and breast cancer, is reviewed. Understanding of the role of these cofactors in virus carcinogenesis may lead to disease prevention through elimination of one or more of the cofactors.", "contents": "The viral etiology of cancer: a realistic approach. The etiology of cancer resembles that of many other diseases in that multiple factors may be required. Because of this, the role or viruses in the etiology of human cancers is especially difficult to assess. When animal tumor systems were used as models, the roles of various predisposing characteristics in virus oncogenesis were elucidated. Extrapolation of these findings to the human diseases suggests the importance of genetics, age, hormones, immune competence, and stress in determining susceptibility to tumor development in individuals infected with an oncogenic virus. The importance of cofactors in induction of those human tumors most strongly associated with virus infection, including Burkitt's lymphoma, nasopharyngeal carcinoma, cerviccal carcinoma, acute myelogenous leukemia, and breast cancer, is reviewed. Understanding of the role of these cofactors in virus carcinogenesis may lead to disease prevention through elimination of one or more of the cofactors."}
{"id": "PMID:195711", "title": "Diet and cancer of endocrine target organs.", "content": "The role of diet in the etiology of cancer of the breast and endometrium is considered. Geographic variation in rates, effects of migration, consequences of exogenous hormone use, and other epidemiologic factors are reviewed. Cancer of the endometrium is related to diet probably through simple caloric excess. The excess is reflected in obesity and the consequent overproduction of estrone, a natural but carcinogenic human estrogen. Diet may also influence breast cancer risk somewhat through the same mechanism. But this mechanism probably would not explain a large proportion of the disease. It is possible that, in addition, some specific dietary factor, for example, saturated fat, is causally related to breast cancer. Such a relationship would probably be mediated through an endocrine mechanism.", "contents": "Diet and cancer of endocrine target organs. The role of diet in the etiology of cancer of the breast and endometrium is considered. Geographic variation in rates, effects of migration, consequences of exogenous hormone use, and other epidemiologic factors are reviewed. Cancer of the endometrium is related to diet probably through simple caloric excess. The excess is reflected in obesity and the consequent overproduction of estrone, a natural but carcinogenic human estrogen. Diet may also influence breast cancer risk somewhat through the same mechanism. But this mechanism probably would not explain a large proportion of the disease. It is possible that, in addition, some specific dietary factor, for example, saturated fat, is causally related to breast cancer. Such a relationship would probably be mediated through an endocrine mechanism."}
{"id": "PMID:195712", "title": "The application in radiation therapy of substances which modify cellular radiation response.", "content": "Compounds to be considered as potential adjuvants in radiotherapy should indicate a strong mechanistic rationale for a differential response between tumor and normal tissues. Drugs which selectively radiosensitize hypoxic cells might be exploited in radiotherapy to increase the sterilization of resistant hypoxic areas of solid tumors which have outgrown their vascular supply. Several compounds have been shown to selectively radiosensitize hypoxic mammalian cells in vitro but their application in clinical studies in presently limited by their toxicity at the high drug dosages required to effect the sensitization. Phase I and Phase II clinical studies have now been completed with the sensitizer, metronidazole. This drug was tolerated by patients at dosages of 6 g/m2 three times a week for 3 weeks with a minimum of side effects, and survival of patients with glioblastoma multiforme treated with fractionated radiotherapy was significantly increased when the sensitizer was used in combination with the radiation. Drugs which selectively radioprotect oxygenated cells might also be exploited in therapy be permitting the use of higher radiation doses and thereby incurring more damage to the resistant hypoxic cells in tumours. Again, drug toxicity appears to be a limiting factor with this approach. If toxicities are not additive, combinations of radiosensitizers and radioprotectors might prove more effective than either individual approach.", "contents": "The application in radiation therapy of substances which modify cellular radiation response. Compounds to be considered as potential adjuvants in radiotherapy should indicate a strong mechanistic rationale for a differential response between tumor and normal tissues. Drugs which selectively radiosensitize hypoxic cells might be exploited in radiotherapy to increase the sterilization of resistant hypoxic areas of solid tumors which have outgrown their vascular supply. Several compounds have been shown to selectively radiosensitize hypoxic mammalian cells in vitro but their application in clinical studies in presently limited by their toxicity at the high drug dosages required to effect the sensitization. Phase I and Phase II clinical studies have now been completed with the sensitizer, metronidazole. This drug was tolerated by patients at dosages of 6 g/m2 three times a week for 3 weeks with a minimum of side effects, and survival of patients with glioblastoma multiforme treated with fractionated radiotherapy was significantly increased when the sensitizer was used in combination with the radiation. Drugs which selectively radioprotect oxygenated cells might also be exploited in therapy be permitting the use of higher radiation doses and thereby incurring more damage to the resistant hypoxic cells in tumours. Again, drug toxicity appears to be a limiting factor with this approach. If toxicities are not additive, combinations of radiosensitizers and radioprotectors might prove more effective than either individual approach."}
{"id": "PMID:195713", "title": "Altered cobalamin distribution in rat hepatomas and in the livers of rats treated with diethylnitrosamine.", "content": "The distribution of cobalamin cofactors was investigated in the livers and tumors of rats bearing transplanted Morris 7777 or 7800 hepatomas, in the livers of rats treated with the hepatocarcinogen diethylnitrosamine, and in normal rats. There was a significant increase in the proportion of methylcobalamin both in livers and tumors from rat bearing the hepatomas 7777 and 7800 compared to the proportion of methylcobalamin in the livers of normal rats. The total cobalamin content of the hepatomas was significantly lower than that of host or control livers. Similarly, the total cobalamin content of the livers from the tumor-bearing rats was less than that in control animals. The administration to rats of an acute dose of diethylnitrosamine led to an 84% increase in the hepatic concentration of methylcobalamin. Chronic administration of diethylnitrosamine slightly increased the hepatic methylcobalamin concentration, but this was not statistically significant. Liver weight was reduced, and the hepatic content of total cobalamin fell to 55% of that in control animals.", "contents": "Altered cobalamin distribution in rat hepatomas and in the livers of rats treated with diethylnitrosamine. The distribution of cobalamin cofactors was investigated in the livers and tumors of rats bearing transplanted Morris 7777 or 7800 hepatomas, in the livers of rats treated with the hepatocarcinogen diethylnitrosamine, and in normal rats. There was a significant increase in the proportion of methylcobalamin both in livers and tumors from rat bearing the hepatomas 7777 and 7800 compared to the proportion of methylcobalamin in the livers of normal rats. The total cobalamin content of the hepatomas was significantly lower than that of host or control livers. Similarly, the total cobalamin content of the livers from the tumor-bearing rats was less than that in control animals. The administration to rats of an acute dose of diethylnitrosamine led to an 84% increase in the hepatic concentration of methylcobalamin. Chronic administration of diethylnitrosamine slightly increased the hepatic methylcobalamin concentration, but this was not statistically significant. Liver weight was reduced, and the hepatic content of total cobalamin fell to 55% of that in control animals."}
{"id": "PMID:195714", "title": "Changes in phosphatidylinositol metabolism correlated to growth state of normal and Rous sarcoma virus-transformed Japanese quail cells.", "content": "Second-passage Japanese quail embryo cell cultures, normal or quantitatively transformed by Rous sarcoma virus, were investigated for phospholipid composition and metabolism. Cells cultivated at low and high population density as well as in the presence or absence of serum, have been compared by chemical analysis and in pulse-chase experiments. No differences in the lipid compositions between the normal and the tumor cells or between cells under different culture conditions were detected. In no case was the metabolism of phosphatidylserine or sphingomyelin affected by culture conditions. The metabolism of the choline and ethanolamine glycerophospholipids, however, differed according to culture conditions, whether cells were normal or transformed. Significantly, in normal cells, the breakdown of [32P]phosphate-labeled phosphatidylinositol was slowed when cell growth was restricted, i.e., at high population density or in medium without serum. This effect was not observed in tumor cells under such culture conditions, and cells were not growth inhibited. Hence, release of [32P]phosphate from phosphatidylinositol is the only parameter in the metabolism of phospholipids observed to correlate with growth.", "contents": "Changes in phosphatidylinositol metabolism correlated to growth state of normal and Rous sarcoma virus-transformed Japanese quail cells. Second-passage Japanese quail embryo cell cultures, normal or quantitatively transformed by Rous sarcoma virus, were investigated for phospholipid composition and metabolism. Cells cultivated at low and high population density as well as in the presence or absence of serum, have been compared by chemical analysis and in pulse-chase experiments. No differences in the lipid compositions between the normal and the tumor cells or between cells under different culture conditions were detected. In no case was the metabolism of phosphatidylserine or sphingomyelin affected by culture conditions. The metabolism of the choline and ethanolamine glycerophospholipids, however, differed according to culture conditions, whether cells were normal or transformed. Significantly, in normal cells, the breakdown of [32P]phosphate-labeled phosphatidylinositol was slowed when cell growth was restricted, i.e., at high population density or in medium without serum. This effect was not observed in tumor cells under such culture conditions, and cells were not growth inhibited. Hence, release of [32P]phosphate from phosphatidylinositol is the only parameter in the metabolism of phospholipids observed to correlate with growth."}
{"id": "PMID:195715", "title": "A putative role for nicotinamide adenine dinucleotide-promoted nuclear protein modification in the antitumor activity of N-methyl-N-nitrosourea.", "content": "Incubation of HeLa cells with the anticancer agent N-methyl-N-nitrosourea (MNU) results in: (a) depression of intracellular nicotinamide adenine dinucleotide levels; (b) stimulation of the chromatin-associated, chromosomal protein-modifying enzyme polyadenosine diphosphoribose [poly(ADP-ribose)] polymerase, which uses nicotinamide adenine dinucleotide as substrate; and (c) some fragmentation of cellular DNA. DNase treatment of HeLa nuclei in vitro also stimulates poly(ADP-ribose) polymerase activity, but not in nuclei derived from MNU-treated cells unless they have been subsequently incubated to allow for recovery from MNU damage. DNA polymerase activity is stimulated in vitro by poly(ADP) ribosylation of nuclear proteins. By using intact nuclei derived from MNU-treated HeLa cells, the repair via elongation of single-strand DNA breaks is demonstrated in vitro. This repair is dependent on DNA polymerase activity and is enhanced by adenosine diphosphate ribosylation of histones. Inhibition of poly(ADP-ribose) polymerase with nicotinamide results in extensive degradation of MNU-damaged DNA. Taken as a whole, these results suggest that poly(ADP-ribose) polymerase may play a role in the repair of alkylation damage to cellular DNA and that the inhibition of this enzyme in vivo might be exploited to potentiate the antitumor and carcinogenic activities of MNU.", "contents": "A putative role for nicotinamide adenine dinucleotide-promoted nuclear protein modification in the antitumor activity of N-methyl-N-nitrosourea. Incubation of HeLa cells with the anticancer agent N-methyl-N-nitrosourea (MNU) results in: (a) depression of intracellular nicotinamide adenine dinucleotide levels; (b) stimulation of the chromatin-associated, chromosomal protein-modifying enzyme polyadenosine diphosphoribose [poly(ADP-ribose)] polymerase, which uses nicotinamide adenine dinucleotide as substrate; and (c) some fragmentation of cellular DNA. DNase treatment of HeLa nuclei in vitro also stimulates poly(ADP-ribose) polymerase activity, but not in nuclei derived from MNU-treated cells unless they have been subsequently incubated to allow for recovery from MNU damage. DNA polymerase activity is stimulated in vitro by poly(ADP) ribosylation of nuclear proteins. By using intact nuclei derived from MNU-treated HeLa cells, the repair via elongation of single-strand DNA breaks is demonstrated in vitro. This repair is dependent on DNA polymerase activity and is enhanced by adenosine diphosphate ribosylation of histones. Inhibition of poly(ADP-ribose) polymerase with nicotinamide results in extensive degradation of MNU-damaged DNA. Taken as a whole, these results suggest that poly(ADP-ribose) polymerase may play a role in the repair of alkylation damage to cellular DNA and that the inhibition of this enzyme in vivo might be exploited to potentiate the antitumor and carcinogenic activities of MNU."}
{"id": "PMID:195719", "title": "A new in vitro cell line established from human oat cell carcinoma of the lung.", "content": "A new tissue culture line, OAT-1975, has been established from explant cultures of human oat cell carcinoma of the lung, characterized and maintained for more than 1 year. The cells grew in a monolayered sheet with 24 hr of population-doubling time and are capable of clonal growth with about 60% plating efficiency. The cells still retain unique morphological and structural characteristics of oat cell carcinoma and showed \"tumor takes\" when transplanted into nude mice and conditioned young Syrian Golden hamsters. The chromosome constitution of the cells is hypertriploid with a modal peak at 74. The permanent growth integrity of the present cell line made it possible to utilize it for cell biological studies. Cell inactivation experiments indicated that the cells are sensitive to X-rays and Mitomycin C when compared to the responses of HeLa S3 cells.", "contents": "A new in vitro cell line established from human oat cell carcinoma of the lung. A new tissue culture line, OAT-1975, has been established from explant cultures of human oat cell carcinoma of the lung, characterized and maintained for more than 1 year. The cells grew in a monolayered sheet with 24 hr of population-doubling time and are capable of clonal growth with about 60% plating efficiency. The cells still retain unique morphological and structural characteristics of oat cell carcinoma and showed \"tumor takes\" when transplanted into nude mice and conditioned young Syrian Golden hamsters. The chromosome constitution of the cells is hypertriploid with a modal peak at 74. The permanent growth integrity of the present cell line made it possible to utilize it for cell biological studies. Cell inactivation experiments indicated that the cells are sensitive to X-rays and Mitomycin C when compared to the responses of HeLa S3 cells."}
{"id": "PMID:195720", "title": "N,N-Dimethylformamide-induced morphological differentiation and reduction of tumorigenicity in cultured mouse rhabdomyosarcoma cells.", "content": "N,N-Dimethylformamide treatment of cell cultures established from a transplantable murine rhabdomyosarcoma-induced morphological differentiation and a marked reduction in the tumorigenicity of the sarcoma cells. Fourteen of 17 CE/J mice receiving injections of inducer-treated cells did not develop tumors after 6 months, whereas all 21 mice receiving inocula of untreated sarcoma cells died of disease between 11 and 31 days. The drug-treated cells did not grow in soft agar; untreated tumor cells grew in the semisolid medium. The untreated tumor cells showed a reduced serum requirement and had a higher saturation density compared to drug-treated cells. Thus the reduction in tumorigenicity of N,N-dimethylformamide-treated cells correlated with certain in vitro growth properties that are more characteristic of normal, mesenchymally derived cells than of sarcoma cells.", "contents": "N,N-Dimethylformamide-induced morphological differentiation and reduction of tumorigenicity in cultured mouse rhabdomyosarcoma cells. N,N-Dimethylformamide treatment of cell cultures established from a transplantable murine rhabdomyosarcoma-induced morphological differentiation and a marked reduction in the tumorigenicity of the sarcoma cells. Fourteen of 17 CE/J mice receiving injections of inducer-treated cells did not develop tumors after 6 months, whereas all 21 mice receiving inocula of untreated sarcoma cells died of disease between 11 and 31 days. The drug-treated cells did not grow in soft agar; untreated tumor cells grew in the semisolid medium. The untreated tumor cells showed a reduced serum requirement and had a higher saturation density compared to drug-treated cells. Thus the reduction in tumorigenicity of N,N-dimethylformamide-treated cells correlated with certain in vitro growth properties that are more characteristic of normal, mesenchymally derived cells than of sarcoma cells."}
{"id": "PMID:195721", "title": "Tumor-associated antigen in bovine and ovine lymphosarcoma.", "content": "Specific tumor-associated antigens were found on the membrane and in the cytoplasm of lymph node cells and peripheral blood lymphocytes (PBL) from cattle and sheep with lymphosarcoma by immunofluorescence tests. Materials from 15 cattle with the adult form of lymphosarcoma were examined. Cytoplasmic antigen was detected in fixed tumor cells from all 15 cases and in PBL from 9 cases tested. Membrane antigen was detected in living cells from 10 of the cases tested. In 3 calf-type cases, cytoplasmic antigen was found in a few (1 to 3%) of the tumor cells, while 1% of the cells from 2 thymic cases had cytoplasmic tumor antigen. In 15 cattle infected with bovine leukemia virus (BLV) but with no evidence of tumor, PBL from 3 cattle had the tumor-associated antigen in the cytoplasm. Negative results were obtained with similar tests done with 9 normal cattle that had no detectable BLV or BLV antibody. Cells from tumors induced with BLV in 5 sheep also had cytoplasmic antigen and membrane tumor-associated antigen. Tumor-associated antigen was found in PBL from 1 or 7 BLV-infected sheep with no clinical evidence of tumor. Similar tests were negative on 4 normal sheep.", "contents": "Tumor-associated antigen in bovine and ovine lymphosarcoma. Specific tumor-associated antigens were found on the membrane and in the cytoplasm of lymph node cells and peripheral blood lymphocytes (PBL) from cattle and sheep with lymphosarcoma by immunofluorescence tests. Materials from 15 cattle with the adult form of lymphosarcoma were examined. Cytoplasmic antigen was detected in fixed tumor cells from all 15 cases and in PBL from 9 cases tested. Membrane antigen was detected in living cells from 10 of the cases tested. In 3 calf-type cases, cytoplasmic antigen was found in a few (1 to 3%) of the tumor cells, while 1% of the cells from 2 thymic cases had cytoplasmic tumor antigen. In 15 cattle infected with bovine leukemia virus (BLV) but with no evidence of tumor, PBL from 3 cattle had the tumor-associated antigen in the cytoplasm. Negative results were obtained with similar tests done with 9 normal cattle that had no detectable BLV or BLV antibody. Cells from tumors induced with BLV in 5 sheep also had cytoplasmic antigen and membrane tumor-associated antigen. Tumor-associated antigen was found in PBL from 1 or 7 BLV-infected sheep with no clinical evidence of tumor. Similar tests were negative on 4 normal sheep."}
{"id": "PMID:195723", "title": "Nuclear protein phosphokinases in normal and neoplastic tissues.", "content": "Protein phosphokinases were isolated from the nuclei of normal and fetal liver and neoplastic tissues. Chromatography on phosphocellulose columns resolved the normal and fetal liver kinases into five reproducible fractions. Each of the fractions differed in optimal divalent cation and substrate requirements. Hepatic proliferation was accompanied by quantitative changes in the kinase activity profiles (with endogenous phosphoprotein as natural substrate). An additional phosphoprotein kinase activity stimulated by Mn2+ was found in the nuclei of malignant cells. This tumor-specific kinase could not be detected either in tumor cytoplasm or in fetal or regenerating liver nuclei. Mn2+-dependent phosphoprotein kinase from Novikoff hepatoma phosphorylated only one major protein band detectable by polyacrylamide gel electrophoresis. This substrate could not be detected in chromatin of normal tissues.", "contents": "Nuclear protein phosphokinases in normal and neoplastic tissues. Protein phosphokinases were isolated from the nuclei of normal and fetal liver and neoplastic tissues. Chromatography on phosphocellulose columns resolved the normal and fetal liver kinases into five reproducible fractions. Each of the fractions differed in optimal divalent cation and substrate requirements. Hepatic proliferation was accompanied by quantitative changes in the kinase activity profiles (with endogenous phosphoprotein as natural substrate). An additional phosphoprotein kinase activity stimulated by Mn2+ was found in the nuclei of malignant cells. This tumor-specific kinase could not be detected either in tumor cytoplasm or in fetal or regenerating liver nuclei. Mn2+-dependent phosphoprotein kinase from Novikoff hepatoma phosphorylated only one major protein band detectable by polyacrylamide gel electrophoresis. This substrate could not be detected in chromatin of normal tissues."}
{"id": "PMID:195724", "title": "Partial purification and characterization of the defective cyclic adenosine 3':5'-monophosphate binding protein kinase from adrenocortical carcinoma.", "content": "Previous studies with isolated adrenocortical carcinoma 494 cells from this laboratory have indicated that the lack of cyclic adenosine 3':5'-monophosphate (cyclic AMP) control in steroidogenesis in the tumor may be due to the defective cyclic AMP-dependent protein kinase enzyme system. This paper describes the partial purification of such an enzyme. Purification was achieved by precipitation of the tumor homogenate with 30 and 45% ammonium sulfate, adsorption on 3% calcium phosphate gel, and chromatography on DEAE-cellulose. Four major protein peaks were isolated. Peak 2 showed cyclic AMP-binding activity and was investigated further for its kinetic properties. In contrast to the cyclic AMP-dependent protein kinase enzyme found in the normal adrenal gland, the enzyme specifically bound cyclic AMP but failed to phosphorylate exogenous histone. It is postulated that lack of the cyclic nucleotide-dependent kinase activity of the protein kinase enzyme may be responsible for the loss of cyclic AMP-regulated corticosterone synthesis in adrenocortical carcinoma cell. It is further shown that the tumor cyclic AMP-binding enzyme undergoes endogenous phosphorylation, which indicates that it has kinase activity but it is independent of cyclic AMP.", "contents": "Partial purification and characterization of the defective cyclic adenosine 3':5'-monophosphate binding protein kinase from adrenocortical carcinoma. Previous studies with isolated adrenocortical carcinoma 494 cells from this laboratory have indicated that the lack of cyclic adenosine 3':5'-monophosphate (cyclic AMP) control in steroidogenesis in the tumor may be due to the defective cyclic AMP-dependent protein kinase enzyme system. This paper describes the partial purification of such an enzyme. Purification was achieved by precipitation of the tumor homogenate with 30 and 45% ammonium sulfate, adsorption on 3% calcium phosphate gel, and chromatography on DEAE-cellulose. Four major protein peaks were isolated. Peak 2 showed cyclic AMP-binding activity and was investigated further for its kinetic properties. In contrast to the cyclic AMP-dependent protein kinase enzyme found in the normal adrenal gland, the enzyme specifically bound cyclic AMP but failed to phosphorylate exogenous histone. It is postulated that lack of the cyclic nucleotide-dependent kinase activity of the protein kinase enzyme may be responsible for the loss of cyclic AMP-regulated corticosterone synthesis in adrenocortical carcinoma cell. It is further shown that the tumor cyclic AMP-binding enzyme undergoes endogenous phosphorylation, which indicates that it has kinase activity but it is independent of cyclic AMP."}
{"id": "PMID:195725", "title": "Biological effects of inhibition of guanine nucleotide synthesis by mycophenolic acid in cultured neuroblastoma cells.", "content": "Mycophenolic acid, an inhibitor of inosinate dehydrogenase, had cytostatic and cytotoxic effects on cultured neuroblastoma cells. Proliferation was inhibited by 50% when cells were incubated with 0.07 micrometerM mycophenolic acid, and cell viability was reduced by 83% when cells were treated with 10 micrometerM mycophenolic acid for 24 hr. Treatment of monolayer cultures with mycophenolic acid reduced intracellular concentrations of guanosine triphosphate by 70% within 3 hr, whereas cytidine triphosphate and uridine triphosphate concentrations were significantly elevated, and adenosine triphosphate concentrations were increased only slightly. Reduction of cellular guanine nucleotides had differential effects on rates of macromolecular synthesis: incorporation of radioactive thymidine into acid-insoluble material was inhibited by mycophenolic acid to a much greater extent than was that of adenosine and leucine. Although proliferation of neuroblastoma cells was inhibited, differentiation, as judged by formation of neuronlike processes in serum-free medium, was unaffected by decreased intracellular concentrations of guanosine triphosphate.", "contents": "Biological effects of inhibition of guanine nucleotide synthesis by mycophenolic acid in cultured neuroblastoma cells. Mycophenolic acid, an inhibitor of inosinate dehydrogenase, had cytostatic and cytotoxic effects on cultured neuroblastoma cells. Proliferation was inhibited by 50% when cells were incubated with 0.07 micrometerM mycophenolic acid, and cell viability was reduced by 83% when cells were treated with 10 micrometerM mycophenolic acid for 24 hr. Treatment of monolayer cultures with mycophenolic acid reduced intracellular concentrations of guanosine triphosphate by 70% within 3 hr, whereas cytidine triphosphate and uridine triphosphate concentrations were significantly elevated, and adenosine triphosphate concentrations were increased only slightly. Reduction of cellular guanine nucleotides had differential effects on rates of macromolecular synthesis: incorporation of radioactive thymidine into acid-insoluble material was inhibited by mycophenolic acid to a much greater extent than was that of adenosine and leucine. Although proliferation of neuroblastoma cells was inhibited, differentiation, as judged by formation of neuronlike processes in serum-free medium, was unaffected by decreased intracellular concentrations of guanosine triphosphate."}
{"id": "PMID:195728", "title": "Extraction and analytic procedures for cytosine arabinoside and 1-beta-D-arabinofuranosyluracil and their 5'-mono-, di-, and tri-phosphates.", "content": "A qualitative and quantitative comparison of perchloric acid (PCA) and trichloroacetic acid (TCA) extraction procedures of biologic material containing cytosine arabinoside (Ara-C) and 1-beta-D-arabinofuranosyluracil (Ara-U) and their biologic 5'-phosphate derivatives revealed definite superiority of the PCA procedure over the TCA procedure. High-pressure liquid chromatography provides rapid and accurate quantitative and qualitative separation of both Ara-C and Ara-U and their 5'-mono-, di-, and tri-phosphates (mu Bondapak NH2 column), or their 5'-mono-, di-, and tri-phosphates without nucleosides (ABX Permaphase columns).", "contents": "Extraction and analytic procedures for cytosine arabinoside and 1-beta-D-arabinofuranosyluracil and their 5'-mono-, di-, and tri-phosphates. A qualitative and quantitative comparison of perchloric acid (PCA) and trichloroacetic acid (TCA) extraction procedures of biologic material containing cytosine arabinoside (Ara-C) and 1-beta-D-arabinofuranosyluracil (Ara-U) and their biologic 5'-phosphate derivatives revealed definite superiority of the PCA procedure over the TCA procedure. High-pressure liquid chromatography provides rapid and accurate quantitative and qualitative separation of both Ara-C and Ara-U and their 5'-mono-, di-, and tri-phosphates (mu Bondapak NH2 column), or their 5'-mono-, di-, and tri-phosphates without nucleosides (ABX Permaphase columns)."}
{"id": "PMID:195729", "title": "Physiologic disposition of cytosine arabinoside and its derivatives in man.", "content": "Enzymatic and clinical pharmacologic studies indicate that 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine (AAFC) is relatively resistant to enzymatic deamination and is not phosphorylated but slowly releases 1-beta-D-arabinofuranosyl-5-fluorocytosine. The latter is deaminated rapidly to 1-beta-D-arabinofuranosyl-5-fluorouracil. After iv injection of labeled cytosine arabinoside (Ara-C), 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine, and AAFC into patients, radioactivity appears in substantial amounts and persists for a prolonged time in the saliva. AAFC slowly penetrates into the cerebrospinal fluid, reaches significant levels, and is retained there for a long time. Ara-C, due to rapid deamination in plasma, does not provide sustained levels of Ara-C in the cerebrospinal fluid. It is likely that this difference between AAFC and Ara-C is due to reduced polarity of the former compound.", "contents": "Physiologic disposition of cytosine arabinoside and its derivatives in man. Enzymatic and clinical pharmacologic studies indicate that 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine (AAFC) is relatively resistant to enzymatic deamination and is not phosphorylated but slowly releases 1-beta-D-arabinofuranosyl-5-fluorocytosine. The latter is deaminated rapidly to 1-beta-D-arabinofuranosyl-5-fluorouracil. After iv injection of labeled cytosine arabinoside (Ara-C), 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine, and AAFC into patients, radioactivity appears in substantial amounts and persists for a prolonged time in the saliva. AAFC slowly penetrates into the cerebrospinal fluid, reaches significant levels, and is retained there for a long time. Ara-C, due to rapid deamination in plasma, does not provide sustained levels of Ara-C in the cerebrospinal fluid. It is likely that this difference between AAFC and Ara-C is due to reduced polarity of the former compound."}
{"id": "PMID:195732", "title": "Isolation of fat cell precursors from adult rat adipose tissue.", "content": "The possible existence of adipocyte precursors in adult rat adipose tissue was investigated. Cells were isolated from the stromal fraction of adipose tissue and were grown in culture. Skin fibroblasts were used as controls. The stromal fraction cells were initially fusiform and proliferated; in culture, they accumulated lipid inclusions, became rounder and acquired an eccentric nucleus. In contrast, the skin fibroblasts from the same rat grown under identical culture conditions, did not exhibit any appreciable lipid accumulation. The doubling time for both the stromal fraction cells and skin fibroblasts was 40-60 h. At confluency, the stromal fraction cells contained 5-7 times more glyceride-glycerol than skin fibroblasts. Thus, adipose tissue of adult rats contains cells with the potential to proliferate and acquire morphological characteristics similar to those of adipocytes.", "contents": "Isolation of fat cell precursors from adult rat adipose tissue. The possible existence of adipocyte precursors in adult rat adipose tissue was investigated. Cells were isolated from the stromal fraction of adipose tissue and were grown in culture. Skin fibroblasts were used as controls. The stromal fraction cells were initially fusiform and proliferated; in culture, they accumulated lipid inclusions, became rounder and acquired an eccentric nucleus. In contrast, the skin fibroblasts from the same rat grown under identical culture conditions, did not exhibit any appreciable lipid accumulation. The doubling time for both the stromal fraction cells and skin fibroblasts was 40-60 h. At confluency, the stromal fraction cells contained 5-7 times more glyceride-glycerol than skin fibroblasts. Thus, adipose tissue of adult rats contains cells with the potential to proliferate and acquire morphological characteristics similar to those of adipocytes."}
{"id": "PMID:195733", "title": "Comparative ultrastructural investigations of the uterine epithelium in the viviparous Salamandra atra Laur. and the ovoviviparous Salamandra salamandra (l.) (amphibia, urodela).", "content": "The uterine epithelium of the viviparous Salamandra atra and the ovoviviparous Salamandra salamandra was studied in non pregnant and ovulating females and in females during different stages of pregnancy. The epithelium of both species is organized in a monolayer. The epithelial cells are characterized by a moderate secretory activity, a variable amount of apical granules which include PAS-positive material and by some apical and basal exo- or endocytotic vesicles. Adjacent cells are joined by junctional complexes. The lateral surfaces form a tortuous boundary with adjoining cells which suggest that the epithelium is involved in transport. Sporadic light cells possess highly variable cytoplasmic inclusions and are not joined with neighbouring cells. Possibly they represent migratory cells. The entire epithelium, except for a small cranial portion of the uterus in S. atra, undergoes no remarkable morphological changes during the different physiological stages examined except that flattened cells seem to be more numerous in pregnant females. The results are discussed with regard to the possible supply of the developing young by the mother.", "contents": "Comparative ultrastructural investigations of the uterine epithelium in the viviparous Salamandra atra Laur. and the ovoviviparous Salamandra salamandra (l.) (amphibia, urodela). The uterine epithelium of the viviparous Salamandra atra and the ovoviviparous Salamandra salamandra was studied in non pregnant and ovulating females and in females during different stages of pregnancy. The epithelium of both species is organized in a monolayer. The epithelial cells are characterized by a moderate secretory activity, a variable amount of apical granules which include PAS-positive material and by some apical and basal exo- or endocytotic vesicles. Adjacent cells are joined by junctional complexes. The lateral surfaces form a tortuous boundary with adjoining cells which suggest that the epithelium is involved in transport. Sporadic light cells possess highly variable cytoplasmic inclusions and are not joined with neighbouring cells. Possibly they represent migratory cells. The entire epithelium, except for a small cranial portion of the uterus in S. atra, undergoes no remarkable morphological changes during the different physiological stages examined except that flattened cells seem to be more numerous in pregnant females. The results are discussed with regard to the possible supply of the developing young by the mother."}
{"id": "PMID:195734", "title": "Ultrastructure of the respiratory epithelium in the lungs of the tortoise, Testudo graeca.", "content": "The respiratory epithelium in the lungs of the tortoise (Testudo graeca) has been studied by electron microscopy. The epithelium consists of a mosaic of two different cell types (here called \"pneumonocytes\"). Type I pneumonocytes are roughly squamous and possess attenuated flanges of cytoplasm which extend over the septal capillaries. Localized cytoplasmic expansions are often present near the periphery of these flanges. Most of the organelles are concentrated in the perinuclear region; the most prominent of these are the mitochondria and osmiophilic inclusions. In contrast, type II pneumonocytes are cuboidal and are richly endowed with organelles including large Golgi complexes, extensive endoplasmic reticulum and numerous inclusion bodies. The morphological evidence suggests that type I pneumonocytes are involved in the secretion of osmiophilic material (presumed to be pulmonary surfactant) and in maintaining the integrity of the air-blood barrier. Type II pneumonocytes appear to be concerned solely with the production of surfactant.", "contents": "Ultrastructure of the respiratory epithelium in the lungs of the tortoise, Testudo graeca. The respiratory epithelium in the lungs of the tortoise (Testudo graeca) has been studied by electron microscopy. The epithelium consists of a mosaic of two different cell types (here called \"pneumonocytes\"). Type I pneumonocytes are roughly squamous and possess attenuated flanges of cytoplasm which extend over the septal capillaries. Localized cytoplasmic expansions are often present near the periphery of these flanges. Most of the organelles are concentrated in the perinuclear region; the most prominent of these are the mitochondria and osmiophilic inclusions. In contrast, type II pneumonocytes are cuboidal and are richly endowed with organelles including large Golgi complexes, extensive endoplasmic reticulum and numerous inclusion bodies. The morphological evidence suggests that type I pneumonocytes are involved in the secretion of osmiophilic material (presumed to be pulmonary surfactant) and in maintaining the integrity of the air-blood barrier. Type II pneumonocytes appear to be concerned solely with the production of surfactant."}
{"id": "PMID:195735", "title": "Investigations on the turnover of adrenocortical mitochondria. VIII. A stereological study of the effect of chronic treatment with ACTH and dexamethasone on the morphology of mitochondria in zona glomerulosa cells of the rat.", "content": "The effects of chronic administration of ACTH and dexamethasone on the morphology of mitochondria in zona glomerulosa cells of the rat adrenal cortex were investigated by stereological techniques. It was found that the volume of the mitochondrial compartment as well as the surface of the outer and inner mitochondrial membranes were significantly increased or decreased in relation to the number of days of ACTH- or dexamethasone-treatment. In ACTH-administered rats, the average volume of individual mitochondria decreased significantly up to the 6th day of treatment and then showed a conspicuous increase from the 6th to the 15th day, whereas in dexamethasone administered animals this parameter, after a small increase during the first 6 days of treatment, displayed a significant decrease. The number of mitochondria per cell showed a dramatic increase during the first 6 days of treatment with ACTH and continued to increase, but only slightly, with the subsequent treatment. In contrast, this parameter showed a parabolic decrease as a function of the duration of treatment in animals receiving dexamethasone. In the light of evidence showing that dexamethasone blocks ACTH-release, these findings are discussed and interpreted to indicate that ACTH is involved in the maintenance and stimulation of the growth and proliferative activity of mitochondria in rat adrenal zona glomerulosa.", "contents": "Investigations on the turnover of adrenocortical mitochondria. VIII. A stereological study of the effect of chronic treatment with ACTH and dexamethasone on the morphology of mitochondria in zona glomerulosa cells of the rat. The effects of chronic administration of ACTH and dexamethasone on the morphology of mitochondria in zona glomerulosa cells of the rat adrenal cortex were investigated by stereological techniques. It was found that the volume of the mitochondrial compartment as well as the surface of the outer and inner mitochondrial membranes were significantly increased or decreased in relation to the number of days of ACTH- or dexamethasone-treatment. In ACTH-administered rats, the average volume of individual mitochondria decreased significantly up to the 6th day of treatment and then showed a conspicuous increase from the 6th to the 15th day, whereas in dexamethasone administered animals this parameter, after a small increase during the first 6 days of treatment, displayed a significant decrease. The number of mitochondria per cell showed a dramatic increase during the first 6 days of treatment with ACTH and continued to increase, but only slightly, with the subsequent treatment. In contrast, this parameter showed a parabolic decrease as a function of the duration of treatment in animals receiving dexamethasone. In the light of evidence showing that dexamethasone blocks ACTH-release, these findings are discussed and interpreted to indicate that ACTH is involved in the maintenance and stimulation of the growth and proliferative activity of mitochondria in rat adrenal zona glomerulosa."}
{"id": "PMID:195736", "title": "Phosphomonoesterases in growth cartilages of the rat.", "content": "Epiphyseal plate cartilage, epiphyseal cartilage, synchondroseal cartilage and mandibular condylar cartilage were studied morphologically and histochemically in 14 days old rats. Ordinary decalcified paraffin sections were stained with hematoxylin & eosin, van Giesons connective tissue stain, or toluidine blue, and used for morphological studies of the different cartilaginous structures. Undecalcified cryostat sections were used for demonstration of acid and alkaline phosphatase. The enzyme activity was tested for at regular intervals during incubation from 15 sec to 120 min. The morphologic study revealed that a marked similarity of construction exists between epiphyseal plate cartilage and synchrondroseal cartilage. The construction of epiphyseal and condylar cartilage differ from that of the other two structures and also differ mutually. With small variations the reaction for both alkaline and acid phosphatase was found to be identical in the zones of erosion, hypertrophy and maturation of the four structures. Intercellularly, acid phosphatase is present in all zones in the synchondroseal and the epiphyseal plate cartilage, while in the epiphyseal and condylar cartilages it is only present in the zones of erosion, hypertrophy and maturation. The identical reaction for acid phosphatase in the epiphyseal and the condylar cartilage is thought, in all likelihood, to be accidental. When kinetic conditions are taken into account, epiphyseal cartilage seems to react like epiphyseal plate and synchondroseal cartilage, while the condylar cartilage takes up an exceptional position among growth cartilages.", "contents": "Phosphomonoesterases in growth cartilages of the rat. Epiphyseal plate cartilage, epiphyseal cartilage, synchondroseal cartilage and mandibular condylar cartilage were studied morphologically and histochemically in 14 days old rats. Ordinary decalcified paraffin sections were stained with hematoxylin & eosin, van Giesons connective tissue stain, or toluidine blue, and used for morphological studies of the different cartilaginous structures. Undecalcified cryostat sections were used for demonstration of acid and alkaline phosphatase. The enzyme activity was tested for at regular intervals during incubation from 15 sec to 120 min. The morphologic study revealed that a marked similarity of construction exists between epiphyseal plate cartilage and synchrondroseal cartilage. The construction of epiphyseal and condylar cartilage differ from that of the other two structures and also differ mutually. With small variations the reaction for both alkaline and acid phosphatase was found to be identical in the zones of erosion, hypertrophy and maturation of the four structures. Intercellularly, acid phosphatase is present in all zones in the synchondroseal and the epiphyseal plate cartilage, while in the epiphyseal and condylar cartilages it is only present in the zones of erosion, hypertrophy and maturation. The identical reaction for acid phosphatase in the epiphyseal and the condylar cartilage is thought, in all likelihood, to be accidental. When kinetic conditions are taken into account, epiphyseal cartilage seems to react like epiphyseal plate and synchondroseal cartilage, while the condylar cartilage takes up an exceptional position among growth cartilages."}
{"id": "PMID:195737", "title": "In vitro and in vivo studies on cytodifferentiation of pituitary clonal cells derived from the epithelium of Rathke's pouch.", "content": "A clonal strain of anterior pituitary cells was derived from Rathke's pouch of the rat. These cells were shown to secrete ACTH, growth hormone and prolactin but no glycoprotein hormones, when grown in vitro. Cells from the 2A8 clone were implanted for one month under kidney capsules or into hypothalami of hypophysectomized female rats. Under the kidney capsule, prominent prolactin cells and poorly developed cells of other types were differentiated as seen in usual pituitary grafts. In hypophysiotrophic areas of the hypothalamus, the grafts were cytodifferentiated into various types of anterior pituitary cells with rich vascularization. These cells had the ultrastructural features indicative of hormone secretion. Increases in body and ovarian weights reflected the secretion of somatotrophic and gonadotrophic hormones. The results obtained indicate that implants of 2A8 clonal cells may differentiate into all types of anterior pituitary cells under the influence of hypothalamic hormones or perhaps some unknown factors present in the general systemic circulation of the rat.", "contents": "In vitro and in vivo studies on cytodifferentiation of pituitary clonal cells derived from the epithelium of Rathke's pouch. A clonal strain of anterior pituitary cells was derived from Rathke's pouch of the rat. These cells were shown to secrete ACTH, growth hormone and prolactin but no glycoprotein hormones, when grown in vitro. Cells from the 2A8 clone were implanted for one month under kidney capsules or into hypothalami of hypophysectomized female rats. Under the kidney capsule, prominent prolactin cells and poorly developed cells of other types were differentiated as seen in usual pituitary grafts. In hypophysiotrophic areas of the hypothalamus, the grafts were cytodifferentiated into various types of anterior pituitary cells with rich vascularization. These cells had the ultrastructural features indicative of hormone secretion. Increases in body and ovarian weights reflected the secretion of somatotrophic and gonadotrophic hormones. The results obtained indicate that implants of 2A8 clonal cells may differentiate into all types of anterior pituitary cells under the influence of hypothalamic hormones or perhaps some unknown factors present in the general systemic circulation of the rat."}
{"id": "PMID:195740", "title": "Mechanism of formation of pseudotypes between vesicular stomatitis virus and murine leukemia virus.", "content": "Pseudotypes of vesicular stomatitis virus (VSV) and Moloney murine leukemia virus (MuLV), defined by their resistance to neutralization by anti-VSV antiserum, are released preferentially at early times after infection of MuLV-producing cells with VSV. At later times, after synthesis of MuLV proteins has been inhibited by the VSV infection, neither MuLV virions nor the VSV (MuLV) pseudotypes are made. Infection of MuLV-producing cells with mutants of VSV having temperature-sensitive lesions in either G or M protein does not generate pseudotypes at nonpermissive temperature, indicating that both proteins are needed for pseudotypes to form. Although the pseudotypes resist neutralization by anti-VSV serum, they are inactivated by anti-VSV serum plus complement, and they can be precipitated by rabbit anti-VSV serum plus goat anti-rabbit IgG. These results, coupled with experiments using a temperature-sensitive mutant of VSV G protein grown at partly restrictive temperature, suggest that small numbers of VSV G protein are obligately incorporated into VSV(MuLV) pseudotypes. There appears to be a stringent requirement for recognition of the viral core by homologous envelope components as the nucleating step in the budding process. Only after such a nucleation can the envelope components of the second virus substitute into the membrane of the budding particle.", "contents": "Mechanism of formation of pseudotypes between vesicular stomatitis virus and murine leukemia virus. Pseudotypes of vesicular stomatitis virus (VSV) and Moloney murine leukemia virus (MuLV), defined by their resistance to neutralization by anti-VSV antiserum, are released preferentially at early times after infection of MuLV-producing cells with VSV. At later times, after synthesis of MuLV proteins has been inhibited by the VSV infection, neither MuLV virions nor the VSV (MuLV) pseudotypes are made. Infection of MuLV-producing cells with mutants of VSV having temperature-sensitive lesions in either G or M protein does not generate pseudotypes at nonpermissive temperature, indicating that both proteins are needed for pseudotypes to form. Although the pseudotypes resist neutralization by anti-VSV serum, they are inactivated by anti-VSV serum plus complement, and they can be precipitated by rabbit anti-VSV serum plus goat anti-rabbit IgG. These results, coupled with experiments using a temperature-sensitive mutant of VSV G protein grown at partly restrictive temperature, suggest that small numbers of VSV G protein are obligately incorporated into VSV(MuLV) pseudotypes. There appears to be a stringent requirement for recognition of the viral core by homologous envelope components as the nucleating step in the budding process. Only after such a nucleation can the envelope components of the second virus substitute into the membrane of the budding particle."}
{"id": "PMID:195741", "title": "Properties of mammalian cells transformed by temperature-sensitive mutants of avian sarcoma virus.", "content": "Fibroblasts from European field vole (Microtus agrestis) and from normal rat kidney (NRK) have been infected by avian sarcoma virus mutants which are temperature-sensitive for the maintenance of transformation. These cells are transformed at 33 degrees C, but show normal cell characteristics in morphology, colony formation in agar, saturation density, sugar uptake and membrane proteins at 39 degrees C and 40 degrees C, the nonpermissive temperatures. Ts mutant virus was rescued from most of the ts transformed cell lines. NRK cells infected by avian sarcoma virus ts mutants and kept at the nonpermissive temperature can be transformed by wild-type avian sarcoma virus. The susceptibility of the temperature-sensitive NRK lines to this transformation is higher than the susceptibility of uninfected NRK at either permissive or nonpermissive temperature.", "contents": "Properties of mammalian cells transformed by temperature-sensitive mutants of avian sarcoma virus. Fibroblasts from European field vole (Microtus agrestis) and from normal rat kidney (NRK) have been infected by avian sarcoma virus mutants which are temperature-sensitive for the maintenance of transformation. These cells are transformed at 33 degrees C, but show normal cell characteristics in morphology, colony formation in agar, saturation density, sugar uptake and membrane proteins at 39 degrees C and 40 degrees C, the nonpermissive temperatures. Ts mutant virus was rescued from most of the ts transformed cell lines. NRK cells infected by avian sarcoma virus ts mutants and kept at the nonpermissive temperature can be transformed by wild-type avian sarcoma virus. The susceptibility of the temperature-sensitive NRK lines to this transformation is higher than the susceptibility of uninfected NRK at either permissive or nonpermissive temperature."}
{"id": "PMID:195743", "title": "Specific folding and contraction of DNA by histones H3 and H4.", "content": "We demonstrate that the arginine-rich histones H3 and H4 can introduce torsional constraints on closed circular DNA with a concomitant compaction of the nucleic acid. SV40 DNA I complexed with H3 and H4 appears relaxed in electron micrographs and contains particles of 75 +/- 10 A in diameter along the DNA. SV40 DNA I is contracted 2.75 +/- 0.25 fold by all the four smaller histones and 2.6 +/- 0.4 fold by H3 and H4 alone. The arginine-rich histones can cause the topological equivalent of unwinding the DNA close to one Watson-Crick turn per particle formed. Spherical nucleoprotein complexes morphologically similar to isolated nu bodies or nucleosomes are obtained by association of H3 and H4 with 140 base pair length DNA isolated from chromatin core particles. These reconstituted particles sediment at 9.8S, as compared to 10.8S for native core particles, and contain a tetramer of the arginine-rich histones. None of these specific alterations in DNA structure is seen om complexing the slightly lysine rich-histones H2A and H2B to DNA. Our data provide further evidence indicating that the arginine-rich histones are the major determinants of the architecture of DNA within the chromatin core particle.", "contents": "Specific folding and contraction of DNA by histones H3 and H4. We demonstrate that the arginine-rich histones H3 and H4 can introduce torsional constraints on closed circular DNA with a concomitant compaction of the nucleic acid. SV40 DNA I complexed with H3 and H4 appears relaxed in electron micrographs and contains particles of 75 +/- 10 A in diameter along the DNA. SV40 DNA I is contracted 2.75 +/- 0.25 fold by all the four smaller histones and 2.6 +/- 0.4 fold by H3 and H4 alone. The arginine-rich histones can cause the topological equivalent of unwinding the DNA close to one Watson-Crick turn per particle formed. Spherical nucleoprotein complexes morphologically similar to isolated nu bodies or nucleosomes are obtained by association of H3 and H4 with 140 base pair length DNA isolated from chromatin core particles. These reconstituted particles sediment at 9.8S, as compared to 10.8S for native core particles, and contain a tetramer of the arginine-rich histones. None of these specific alterations in DNA structure is seen om complexing the slightly lysine rich-histones H2A and H2B to DNA. Our data provide further evidence indicating that the arginine-rich histones are the major determinants of the architecture of DNA within the chromatin core particle."}
{"id": "PMID:195744", "title": "Distribution of concanavalin A in fibroblasts: direct endocytosis versus surface capping.", "content": "Indirect immunofluorescence of intact or acetone-extracted cells has allowed us to distinguish concanavalin A (Con A) which is associated with the plasma membrane of CHO cells from Con A which has been interiorized. We find that Con A is directly endocytized by these cells with no intervening stage of plasma membrane aggregation. The lectin accumulations observed by direct fluorescence are actually cytoplasmic collections of pinosomes which contain Con A. Only in a small fraction of CHO cells are true plasma membrane aggregates, or caps, found. This predominance of direct pinocytic interiorization over capping was not affected by dibutyryl cAMP or by treatments which can disrupt microtubules, including cold shock or exposure of the cells to anti-mitotic agents. Cytochalasin B, however, inhibited the uptake of Con A and at the same time promoted the formation of large surface aggregates of the lectin, or minicaps. Capping may reflect a competition between aggregation in the plane of the membrane and direct interiorization of bound lectin. Surface cap formation may be a characteristic process of cells with very low endocytic rates, such as lymphocytes.", "contents": "Distribution of concanavalin A in fibroblasts: direct endocytosis versus surface capping. Indirect immunofluorescence of intact or acetone-extracted cells has allowed us to distinguish concanavalin A (Con A) which is associated with the plasma membrane of CHO cells from Con A which has been interiorized. We find that Con A is directly endocytized by these cells with no intervening stage of plasma membrane aggregation. The lectin accumulations observed by direct fluorescence are actually cytoplasmic collections of pinosomes which contain Con A. Only in a small fraction of CHO cells are true plasma membrane aggregates, or caps, found. This predominance of direct pinocytic interiorization over capping was not affected by dibutyryl cAMP or by treatments which can disrupt microtubules, including cold shock or exposure of the cells to anti-mitotic agents. Cytochalasin B, however, inhibited the uptake of Con A and at the same time promoted the formation of large surface aggregates of the lectin, or minicaps. Capping may reflect a competition between aggregation in the plane of the membrane and direct interiorization of bound lectin. Surface cap formation may be a characteristic process of cells with very low endocytic rates, such as lymphocytes."}
{"id": "PMID:195749", "title": "[Intestinal vasoactive peptide receptors in enterocytes : specific binding and stimulation of cyclic AMP].", "content": "Receptors for the vasoactive intestinal peptide (VIP) were characterized on enterocytes isolated from Rat small intestine. Native VIP inhibited competitively the binding of 125I-VIP to enterocytes and strongly stimulated cyclic AMP production; both these effects were observed for concentrations of VIP as low as 0.5-1.0 ng/ml (0.15-0.30 nM) which are compatible with the VIP concentration in the gut.", "contents": "[Intestinal vasoactive peptide receptors in enterocytes : specific binding and stimulation of cyclic AMP]. Receptors for the vasoactive intestinal peptide (VIP) were characterized on enterocytes isolated from Rat small intestine. Native VIP inhibited competitively the binding of 125I-VIP to enterocytes and strongly stimulated cyclic AMP production; both these effects were observed for concentrations of VIP as low as 0.5-1.0 ng/ml (0.15-0.30 nM) which are compatible with the VIP concentration in the gut."}
{"id": "PMID:195750", "title": "[Biological and biochemical characterization of a new isolate of baboon Papio papio endogenous type C virus].", "content": "A new strain of Baboon Papio papio endogeneous type C virus was isolated from the testis of an animal of this species. The strain was characterized biochemically and biologically. It presents a host-range different from that of the prototype strain of the same virus.", "contents": "[Biological and biochemical characterization of a new isolate of baboon Papio papio endogenous type C virus]. A new strain of Baboon Papio papio endogeneous type C virus was isolated from the testis of an animal of this species. The strain was characterized biochemically and biologically. It presents a host-range different from that of the prototype strain of the same virus."}
{"id": "PMID:195752", "title": "A simple and sensitive method for estimating the concentration and synthesis of 5-phosphoribosyl 1-pyrophosphate in red blood cells.", "content": "A method is presented for the determination of 5-phosphoribosyl 1-pyrophosphate (PRPP), which is based on the release of 14CO2 from [carboxyl-14C]-orotic acid by the consecutive action of orotate phosphoribosyltransferase and orotidine-5'-monophosphate decarboxylase. The assay is simpler and less time-consuming than most methods currently employed and is equally sensitive. The method proved to be suitable for measuring low concentrations of PRPP such as found in human erythrocytes and fibroblasts. An increased PRPP concentration was observed in erythrocytes from patients with partial or complete deficiency of hypoxanthine-guanine phospho-ribosyltransferase. frp, sp,e (but not all) gouty patients and from a patient with deficiency of purine nucleoside phosphorylase. PRPP synthetase activity was measured with a method similar to the assay for PRPP. In erythrocytes with an increased PRPP concentration, PRPP synthetase activity was found to be normal at both optimal and suboptimal substrate concentrations.", "contents": "A simple and sensitive method for estimating the concentration and synthesis of 5-phosphoribosyl 1-pyrophosphate in red blood cells. A method is presented for the determination of 5-phosphoribosyl 1-pyrophosphate (PRPP), which is based on the release of 14CO2 from [carboxyl-14C]-orotic acid by the consecutive action of orotate phosphoribosyltransferase and orotidine-5'-monophosphate decarboxylase. The assay is simpler and less time-consuming than most methods currently employed and is equally sensitive. The method proved to be suitable for measuring low concentrations of PRPP such as found in human erythrocytes and fibroblasts. An increased PRPP concentration was observed in erythrocytes from patients with partial or complete deficiency of hypoxanthine-guanine phospho-ribosyltransferase. frp, sp,e (but not all) gouty patients and from a patient with deficiency of purine nucleoside phosphorylase. PRPP synthetase activity was measured with a method similar to the assay for PRPP. In erythrocytes with an increased PRPP concentration, PRPP synthetase activity was found to be normal at both optimal and suboptimal substrate concentrations."}
{"id": "PMID:195753", "title": "Studies on a beta-migrating high density lipoprotein.", "content": "An unusual serum lipoprotein (Lp) profile was detected in a Japanese family. A double beta-Lp was observed when serum was subjected to polyacrylamide gel electrophoresis. The slower migrating beta-Lp was identified as a subfraction of high density lipoprotein (HDL). It was present in the d 1.063--1.21 fraction, migrated to the position designated as the midband L.1 (sinking pre-beta-lipoprotein) by Mead, M.G. and Dangerfield, W.G. (1974) (Clin. Chim. Acta 51, 173--182) [1], and reacted against human anti-beta-Lp antiserum. This lipoprotein contained greater amounts of triglyceride than the usual beta-lipoprotein and could not be clearly detected by paper electrophoresis. Individuals exhibiting this high density midband lipoprotein appeared to be heterozygous for an autosomal dominant gene. Although other reports have indicated the possibility of a positive association between the occurrence of serum lipoproteins with unusual eletrophoretic mobility and premature ischemic heart disease, no such correlation was demonstrable in these subjects.", "contents": "Studies on a beta-migrating high density lipoprotein. An unusual serum lipoprotein (Lp) profile was detected in a Japanese family. A double beta-Lp was observed when serum was subjected to polyacrylamide gel electrophoresis. The slower migrating beta-Lp was identified as a subfraction of high density lipoprotein (HDL). It was present in the d 1.063--1.21 fraction, migrated to the position designated as the midband L.1 (sinking pre-beta-lipoprotein) by Mead, M.G. and Dangerfield, W.G. (1974) (Clin. Chim. Acta 51, 173--182) [1], and reacted against human anti-beta-Lp antiserum. This lipoprotein contained greater amounts of triglyceride than the usual beta-lipoprotein and could not be clearly detected by paper electrophoresis. Individuals exhibiting this high density midband lipoprotein appeared to be heterozygous for an autosomal dominant gene. Although other reports have indicated the possibility of a positive association between the occurrence of serum lipoproteins with unusual eletrophoretic mobility and premature ischemic heart disease, no such correlation was demonstrable in these subjects."}
{"id": "PMID:195754", "title": "Lipoprotein concentrations in untreated adult onset diabetes mellitus and the relationship of the fasting plasma triglyceride concentration to insulin secretion.", "content": "Plasma lipoprotein concentrations in 64 untreated adult onset diabetics were compared to the lipoprotein levels found in non diabetics. No significant difference was found. The relationship of the fasting plasma triglyceride concentration to the plasma immunoreaction insulin response to 50 g glucose orally was investigated. Using correlation analysis a significant and insulin response in the non diabetics but not in the diabetics.", "contents": "Lipoprotein concentrations in untreated adult onset diabetes mellitus and the relationship of the fasting plasma triglyceride concentration to insulin secretion. Plasma lipoprotein concentrations in 64 untreated adult onset diabetics were compared to the lipoprotein levels found in non diabetics. No significant difference was found. The relationship of the fasting plasma triglyceride concentration to the plasma immunoreaction insulin response to 50 g glucose orally was investigated. Using correlation analysis a significant and insulin response in the non diabetics but not in the diabetics."}
{"id": "PMID:195756", "title": "'Big ACTH' and calcitonin in an ectopic hormone secreting tumour of the liver.", "content": "A young man presented with rapidly developing Cushing's syndrome which was due to the ectopic secretion of ACTH and beta-MSH-like material from hepatic tumour deposits, possibly originating from biliary radicals. This association of the ectopic ACTH syndrome has not previously been described. During the 22 month course of the illness the plasma immunoreactive ACTH and 'beta-MSH' concentrations rose by logarithmic progression. The plasma calcitonin concentration was also raised but did not change during the last 12 months. At any stage of the illness the plasma concentration of the ecotopically produced hormones was stable except that after hydrocortisone there were inconstant variations. During the course of the illness the ectopic ACTH became biologically less potent. This ineffectural ACTH was present in the plasma, in the tumour, and in the medium in which the tumour was cultured, in a large molecular weight form. This 'big ACTH' differed from the normal ACTH found in the patient's pituitary and from authentic ACTH in its immunochemical character: the C-terminal antigenic determinant (33-39 region of ACTH) was masked in the large molecular weight form but was uncovered after extraction in neutral buffer and this 'big ACTH' was more readily extracted from the tumour at pH 7.0. The tumour tissue also contained immunoreactive beta-MSH-like material and immunoreactive calcitonin which resembled calcitonin M chromatographically.", "contents": "'Big ACTH' and calcitonin in an ectopic hormone secreting tumour of the liver. A young man presented with rapidly developing Cushing's syndrome which was due to the ectopic secretion of ACTH and beta-MSH-like material from hepatic tumour deposits, possibly originating from biliary radicals. This association of the ectopic ACTH syndrome has not previously been described. During the 22 month course of the illness the plasma immunoreactive ACTH and 'beta-MSH' concentrations rose by logarithmic progression. The plasma calcitonin concentration was also raised but did not change during the last 12 months. At any stage of the illness the plasma concentration of the ecotopically produced hormones was stable except that after hydrocortisone there were inconstant variations. During the course of the illness the ectopic ACTH became biologically less potent. This ineffectural ACTH was present in the plasma, in the tumour, and in the medium in which the tumour was cultured, in a large molecular weight form. This 'big ACTH' differed from the normal ACTH found in the patient's pituitary and from authentic ACTH in its immunochemical character: the C-terminal antigenic determinant (33-39 region of ACTH) was masked in the large molecular weight form but was uncovered after extraction in neutral buffer and this 'big ACTH' was more readily extracted from the tumour at pH 7.0. The tumour tissue also contained immunoreactive beta-MSH-like material and immunoreactive calcitonin which resembled calcitonin M chromatographically."}
{"id": "PMID:195759", "title": "Intractable diarrhoea of infancy.", "content": "The intractable diarrhoea syndrome of infancy continues to be a major diagnostic and therapeutic challenge to the paediatrician and paediatric gastroenterologist. A carefully organized, staged approach to diagnosis will provide the best method of identifying those infants in whom a specific aetiology exists and for whom specific therapy is often available. Regardless of aetiology, however, the early use of appropriate nutritional support will not only reduce morbidity and mortality in these infants, but will prevent the development of many of the secondary consequences of malnutrition. The physician must compulsively pay attention to the details of daily management and provide an organized approach to diagnosis and treatment in order to improve the outcome of infants with intractable diarrhoea.", "contents": "Intractable diarrhoea of infancy. The intractable diarrhoea syndrome of infancy continues to be a major diagnostic and therapeutic challenge to the paediatrician and paediatric gastroenterologist. A carefully organized, staged approach to diagnosis will provide the best method of identifying those infants in whom a specific aetiology exists and for whom specific therapy is often available. Regardless of aetiology, however, the early use of appropriate nutritional support will not only reduce morbidity and mortality in these infants, but will prevent the development of many of the secondary consequences of malnutrition. The physician must compulsively pay attention to the details of daily management and provide an organized approach to diagnosis and treatment in order to improve the outcome of infants with intractable diarrhoea."}
{"id": "PMID:195760", "title": "Interaction of isolated Lp(a) lipoprotein with calcium ions and glycosaminoglycans in vitro.", "content": "The interaction between the lipoprotein carrying the Lp(a) antigen, i.e. the Lp(a) lipoprotein, and agarose gels substituted with glycosaminoglycans, as well as the precipitation of the Lp(a) lipoprotein by Ca++ were studied. Comparisons between Lp(a) lipoprotein and other serum lipoproteins were conducted. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) were bound to the tested glycosaminoglycans at low ionic strength of sodium chloride, but no binding was found with the Lp(a) lipoprotein. However, Ca++ as a divalent buffer cation gave a precipitating Ca++-Lp(a) lipoprotein complex even at a physiological Ca++ concentration. VLDL and LDL were not precipitated under these conditions. These findings may be of interest in relation to the previously reported higher frequency of the phenotype Lp(a+) in subjects with coronary heart disease.", "contents": "Interaction of isolated Lp(a) lipoprotein with calcium ions and glycosaminoglycans in vitro. The interaction between the lipoprotein carrying the Lp(a) antigen, i.e. the Lp(a) lipoprotein, and agarose gels substituted with glycosaminoglycans, as well as the precipitation of the Lp(a) lipoprotein by Ca++ were studied. Comparisons between Lp(a) lipoprotein and other serum lipoproteins were conducted. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) were bound to the tested glycosaminoglycans at low ionic strength of sodium chloride, but no binding was found with the Lp(a) lipoprotein. However, Ca++ as a divalent buffer cation gave a precipitating Ca++-Lp(a) lipoprotein complex even at a physiological Ca++ concentration. VLDL and LDL were not precipitated under these conditions. These findings may be of interest in relation to the previously reported higher frequency of the phenotype Lp(a+) in subjects with coronary heart disease."}
{"id": "PMID:195763", "title": "Unchanged hormone sensitivity of rat fat cell adenylate cyclase in uremia.", "content": "The sensitivity to hormones of the fat cell adenylate cyclase system was tested in uremic rats and in pair-fed control animals. Basal enzyme activities averaged 1.25 nmoles of cAMP formed per mg protein per 15 min in controls compared to 1.30 nmoles cAMP/mg protein/15 min in fat cell ghosts obtained from uremic rats. NaF caused an approximately 4-fold stimulation of enzyme activities in both systems. It was shown that parathyroid hormone should be included amongst the hormones which act as stimulators of the enzyme system. The responsiveness of the rat fat cell adenylate cyclase system towards saturating concentrations of ACTH, glucagon, epinephrine and parathyroid hormone was not altered in the presence of chronic renal failure.", "contents": "Unchanged hormone sensitivity of rat fat cell adenylate cyclase in uremia. The sensitivity to hormones of the fat cell adenylate cyclase system was tested in uremic rats and in pair-fed control animals. Basal enzyme activities averaged 1.25 nmoles of cAMP formed per mg protein per 15 min in controls compared to 1.30 nmoles cAMP/mg protein/15 min in fat cell ghosts obtained from uremic rats. NaF caused an approximately 4-fold stimulation of enzyme activities in both systems. It was shown that parathyroid hormone should be included amongst the hormones which act as stimulators of the enzyme system. The responsiveness of the rat fat cell adenylate cyclase system towards saturating concentrations of ACTH, glucagon, epinephrine and parathyroid hormone was not altered in the presence of chronic renal failure."}
{"id": "PMID:195764", "title": "The role of prostaglandins in experimental arthritis in the rat.", "content": "In the experimental model of streptococcal CFE-induced arthritis, PGE and PGF concentrations rise significantly. This is due to an increase both in the substrate concentration and the enzyme activity for PG biosynthesis. Indomethacin therapy inhibited PG synthesis and diminished some of the gross, but not the histological, features of the inflammatory response. These results lend further support to the contention that the beneficial effect of indomethacin in arthritis is due to inhibition of PG biosynthesis.", "contents": "The role of prostaglandins in experimental arthritis in the rat. In the experimental model of streptococcal CFE-induced arthritis, PGE and PGF concentrations rise significantly. This is due to an increase both in the substrate concentration and the enzyme activity for PG biosynthesis. Indomethacin therapy inhibited PG synthesis and diminished some of the gross, but not the histological, features of the inflammatory response. These results lend further support to the contention that the beneficial effect of indomethacin in arthritis is due to inhibition of PG biosynthesis."}
{"id": "PMID:195762", "title": "The effect of apomorphine and clonidine on locomotor activity in mice after long term treatment with haloperidol.", "content": "1. Mice were given haloperidol (approximately 3 mg.kg-1 day-1) or vehicle for 21 days and then withdrawn from the drug. All tests were performed 4 days after withdrawal. 2. Haloperidol treated mice (premedicated with reserpine plus alpha-methyl-p-tyrosine) displayed an increased locomotor response to apomorphine and to apomorphine plus clonidine, but neither haloperidol- or vehicle-treated animals revealed any stimulant response to clonidine. 3. In mice which had not been pretreated with reserpine plus alpha-methyl-p-tyrosine, clonidine produced a significant stimulation of locomotor activity in animals withdrawn from haloperidol but not in those withdrawn from the vehicle. Phenoxybenzamine blocked the locomotor stimulat difference between these two groups, but did not completely antagonized the stimulant effect of clonidine in mice withdrawn from haloperidol. Pimozide was largely effective in blocking the clonidine-induced stimulation. Co-administration of phenoxybenzamine and pimozide was completely effective in blocking the stimulant effect of clonidine in mice withdrawn from haloperidol. 4. The evidence for a change in catecholamine receptor sensitivity was supported compared to the vehicle-treated animals. 5. The data suggest that there is a change in the functional responsiveness of both adrenergic and dopaminergic receptors after withdrawal from long term haloperidol treatment.", "contents": "The effect of apomorphine and clonidine on locomotor activity in mice after long term treatment with haloperidol. 1. Mice were given haloperidol (approximately 3 mg.kg-1 day-1) or vehicle for 21 days and then withdrawn from the drug. All tests were performed 4 days after withdrawal. 2. Haloperidol treated mice (premedicated with reserpine plus alpha-methyl-p-tyrosine) displayed an increased locomotor response to apomorphine and to apomorphine plus clonidine, but neither haloperidol- or vehicle-treated animals revealed any stimulant response to clonidine. 3. In mice which had not been pretreated with reserpine plus alpha-methyl-p-tyrosine, clonidine produced a significant stimulation of locomotor activity in animals withdrawn from haloperidol but not in those withdrawn from the vehicle. Phenoxybenzamine blocked the locomotor stimulat difference between these two groups, but did not completely antagonized the stimulant effect of clonidine in mice withdrawn from haloperidol. Pimozide was largely effective in blocking the clonidine-induced stimulation. Co-administration of phenoxybenzamine and pimozide was completely effective in blocking the stimulant effect of clonidine in mice withdrawn from haloperidol. 4. The evidence for a change in catecholamine receptor sensitivity was supported compared to the vehicle-treated animals. 5. The data suggest that there is a change in the functional responsiveness of both adrenergic and dopaminergic receptors after withdrawal from long term haloperidol treatment."}
{"id": "PMID:195777", "title": "Synthesis of estradiol-17 beta by Sertoli cells in culture: stimulation by FSH and dibutyryl cyclic AMP.", "content": "Sertoli cells isolated from the testes of 18 to 20-day old rats synthesize estradiol-17 beta when grown in primary culture in the presence of testosterone (5 X 10(-7) M). After an initial lag phase of about 2 hours, follicle-stimulating hormone (FSH) stimulates synthesis of estradiol up to 50-fold, synthesis being approximately linear for 24 hours when medium is changed every 2-6 hours. Luteinizing hormone (LH) causes only a marginal stimulation, at concentrations consistent with contamination with FSH. Dibutyryl cyclic 3',5'-adenosine monophosphate (dbcAMP) (10(-4)M) mimicks the effect of FSH. No significant synthesis occurs in the absence of steroid substrate or in the presence of pregnenolone (5 X 10(-7) M). When cells are pre-incubated for 24 hours with FSH in the absence of testosterone, addition of testosterone results in an immediated increase in estradiol synthesis without a lag phase, suggesting that FSH or dbcAMP are capable of inducing the conditions necessary for stimulation in the absence of testosterone. These observations provide the first direct evidence of estradiol-17 beta synthesis by Sertoli cells from normal animals, and offer evidence that synthesis of this steroid is regulated at the level of the aromatizing enzyme system by FSH and cyclic AMP.", "contents": "Synthesis of estradiol-17 beta by Sertoli cells in culture: stimulation by FSH and dibutyryl cyclic AMP. Sertoli cells isolated from the testes of 18 to 20-day old rats synthesize estradiol-17 beta when grown in primary culture in the presence of testosterone (5 X 10(-7) M). After an initial lag phase of about 2 hours, follicle-stimulating hormone (FSH) stimulates synthesis of estradiol up to 50-fold, synthesis being approximately linear for 24 hours when medium is changed every 2-6 hours. Luteinizing hormone (LH) causes only a marginal stimulation, at concentrations consistent with contamination with FSH. Dibutyryl cyclic 3',5'-adenosine monophosphate (dbcAMP) (10(-4)M) mimicks the effect of FSH. No significant synthesis occurs in the absence of steroid substrate or in the presence of pregnenolone (5 X 10(-7) M). When cells are pre-incubated for 24 hours with FSH in the absence of testosterone, addition of testosterone results in an immediated increase in estradiol synthesis without a lag phase, suggesting that FSH or dbcAMP are capable of inducing the conditions necessary for stimulation in the absence of testosterone. These observations provide the first direct evidence of estradiol-17 beta synthesis by Sertoli cells from normal animals, and offer evidence that synthesis of this steroid is regulated at the level of the aromatizing enzyme system by FSH and cyclic AMP."}
{"id": "PMID:195778", "title": "Angiofibromata mimicking viral warts.", "content": "A case is presented of an otherwise healthy woman with a relatively normal childhood and adult life and no evidence of any congenital anomaly, who at the age of twenty-seven, suddenly, almost explosively, had development of verruca-like lesions of the face. It is well to remember that the clinically obvious is not always the obvious, things are not always what they seem, and verrucae are not always viral warts.", "contents": "Angiofibromata mimicking viral warts. A case is presented of an otherwise healthy woman with a relatively normal childhood and adult life and no evidence of any congenital anomaly, who at the age of twenty-seven, suddenly, almost explosively, had development of verruca-like lesions of the face. It is well to remember that the clinically obvious is not always the obvious, things are not always what they seem, and verrucae are not always viral warts."}
{"id": "PMID:195783", "title": "[Hypertrophic obstructive cardiomyopathy and lentiginosis (author's transl)].", "content": "Progressive cardiomyopathic lentiginosis was first described in 1972 by Polani and Moynahan. It is characterised by pigmentation of the skin (multiple symmetrical lentigines), hypertrophic obstructive cardiomyopathy and retarded growth. There may also be mental retardation. All characteristics of the syndrome were present in a 46-year-old woman. In addition there were also other features: lentigo developed at only 35 years of age, there was hypertelorism, thoracic kyphosis, and intermittent severe depression. Cyclic adenosine monophosphate in plasma was raised to 90.5 nmol/1.", "contents": "[Hypertrophic obstructive cardiomyopathy and lentiginosis (author's transl)]. Progressive cardiomyopathic lentiginosis was first described in 1972 by Polani and Moynahan. It is characterised by pigmentation of the skin (multiple symmetrical lentigines), hypertrophic obstructive cardiomyopathy and retarded growth. There may also be mental retardation. All characteristics of the syndrome were present in a 46-year-old woman. In addition there were also other features: lentigo developed at only 35 years of age, there was hypertelorism, thoracic kyphosis, and intermittent severe depression. Cyclic adenosine monophosphate in plasma was raised to 90.5 nmol/1."}
{"id": "PMID:195785", "title": "[Histological results of lumps excised from the breast after aspiration (author's transl)].", "content": "In 614 breasts tumours assumed to be harmless cysts on palpation were aspirated. In 430 cases aspiration was the definitive treatment. In the other 184 cases excision was necessary in order to obtain histology. 11 cysts were radiologically suspect after air filling. In one case excision demonstrated an undifferentiated milk duct carcinoma. 12 cysts had radiologically suspicious areas outside their margins. In 4 cases lobular carcinoma in situ was present. 161 excisions were necessary because no fluid was aspirated at puncture of the tumour. In 10 cases histology showed malignancy: half of these were metastases from a known primary tumour and half were primary breast carcinomas. Out of 17 precancerous states neoplasia could be demonstrated in two cases in addition to papillary and proliferative duct changes. We have classified this neoplasia as lobular carcinoma in situ.", "contents": "[Histological results of lumps excised from the breast after aspiration (author's transl)]. In 614 breasts tumours assumed to be harmless cysts on palpation were aspirated. In 430 cases aspiration was the definitive treatment. In the other 184 cases excision was necessary in order to obtain histology. 11 cysts were radiologically suspect after air filling. In one case excision demonstrated an undifferentiated milk duct carcinoma. 12 cysts had radiologically suspicious areas outside their margins. In 4 cases lobular carcinoma in situ was present. 161 excisions were necessary because no fluid was aspirated at puncture of the tumour. In 10 cases histology showed malignancy: half of these were metastases from a known primary tumour and half were primary breast carcinomas. Out of 17 precancerous states neoplasia could be demonstrated in two cases in addition to papillary and proliferative duct changes. We have classified this neoplasia as lobular carcinoma in situ."}
{"id": "PMID:195788", "title": "[Oestrogen treatment of girls with increased growth (author's transl)].", "content": "Forty-one pubescent girls of constitutionally tall stature were given conjugated oestrogens for a continuous period averaging twenty-two months. Oral progestin was also given, daily for five days during the second half of each menstrual cycle. Average predicted height of the girls was 186.5 cm, average final height was only 179.2 cm. In half of the girls in whom treatment had been started before menarche the height reduction was 2 cm greater than in those started after menarche. There were no severe side effects. Extreme care should be taken to limit strictly the indications for this treatment. Only girls with a growth prognosis above 183 cm should be considered. Therapeutic overstimulation of the endometrium must be avoided. Earlier views that the cessation of growth under oestrogen is due to early epiphyseal closure have been shown to be wrong. Growth frequently ceases long before epiphyseal closure. Reduction of somatomedin production was found to be the cause. The average serum somatomedin level fell to 56.9% of basal concentration after six months' treatment. At the same time, the circadian profile of growth hormone indicated a threefold increase above basal level. This phenomenon probably reflects a negative feedback mechanism between growth hormone and somatomedin.", "contents": "[Oestrogen treatment of girls with increased growth (author's transl)]. Forty-one pubescent girls of constitutionally tall stature were given conjugated oestrogens for a continuous period averaging twenty-two months. Oral progestin was also given, daily for five days during the second half of each menstrual cycle. Average predicted height of the girls was 186.5 cm, average final height was only 179.2 cm. In half of the girls in whom treatment had been started before menarche the height reduction was 2 cm greater than in those started after menarche. There were no severe side effects. Extreme care should be taken to limit strictly the indications for this treatment. Only girls with a growth prognosis above 183 cm should be considered. Therapeutic overstimulation of the endometrium must be avoided. Earlier views that the cessation of growth under oestrogen is due to early epiphyseal closure have been shown to be wrong. Growth frequently ceases long before epiphyseal closure. Reduction of somatomedin production was found to be the cause. The average serum somatomedin level fell to 56.9% of basal concentration after six months' treatment. At the same time, the circadian profile of growth hormone indicated a threefold increase above basal level. This phenomenon probably reflects a negative feedback mechanism between growth hormone and somatomedin."}
{"id": "PMID:195789", "title": "Hexoprenaline: a review of its pharmacological properties and therapeutic efficacy with particular reference to asthma.", "content": "Hexoprenaline1, N,N-[2-(3,4-dihydroxyphenyl)-2-hydroxyethyl] hexamethyl-enediamine, sulphate is a selective beta2-adrenoreceptor agonist which is active in man as a bronchodilator by the oral or intravenous routes and by inhalation. It is indicated for use in the treatment of bronchospasm associated with obstructive airways diseases, including asthma, bronchitis and emphysema. Clinical experience and double-blind studies have established that hexoprenaline is an effective bronchodilator. It major advantage over many other many other brochodilators of equal efficacy is its generally low production of side-effects, particularly tremor, palptitations, and tachycardia. In comparative trials, it has generally been rated as superior to orciprenaline or trimetoquinol, but comparisons with salbutamol have provided equivocal results. Oral hexoprenaline was superior to fenoterol as long-term maintenance therapy is asthma, principally because its somewhat lesser bronchodilatory effects were more than compensated for by a lesser incidence of side-effects.", "contents": "Hexoprenaline: a review of its pharmacological properties and therapeutic efficacy with particular reference to asthma. Hexoprenaline1, N,N-[2-(3,4-dihydroxyphenyl)-2-hydroxyethyl] hexamethyl-enediamine, sulphate is a selective beta2-adrenoreceptor agonist which is active in man as a bronchodilator by the oral or intravenous routes and by inhalation. It is indicated for use in the treatment of bronchospasm associated with obstructive airways diseases, including asthma, bronchitis and emphysema. Clinical experience and double-blind studies have established that hexoprenaline is an effective bronchodilator. It major advantage over many other many other brochodilators of equal efficacy is its generally low production of side-effects, particularly tremor, palptitations, and tachycardia. In comparative trials, it has generally been rated as superior to orciprenaline or trimetoquinol, but comparisons with salbutamol have provided equivocal results. Oral hexoprenaline was superior to fenoterol as long-term maintenance therapy is asthma, principally because its somewhat lesser bronchodilatory effects were more than compensated for by a lesser incidence of side-effects."}
{"id": "PMID:195791", "title": "[Aspects of bonding and fusing of materials meltable by lasers (caries prophylaxis and therapy)].", "content": "Experiments are described which aim to combine a protective cover with the enamel. Borium proved to be a good absorbtive mediator and phosphate glass was well suited as ground substance.", "contents": "[Aspects of bonding and fusing of materials meltable by lasers (caries prophylaxis and therapy)]. Experiments are described which aim to combine a protective cover with the enamel. Borium proved to be a good absorbtive mediator and phosphate glass was well suited as ground substance."}
{"id": "PMID:195793", "title": "Stability of nuclear triiodothyronine binding sites.", "content": "Rat liver nuclei have recently been shown to possess limited, high affinity binding sites for triiodothyronine, only a fraction of which are believed to be filled in vivo. We have found that preincubation of nuclei in the absence of added triiodothyronine leads to a rapid decrease in binding capacity. This loss of binding sites is considerably faster at 37 C than at 4 C. On the other hand, once binding equilibrium is reached between nuclear bound and free triiodothyronine the level of binding does not change during the time in which a considerable loss of binding had occurred when nuclei were preincubated in the absence of hormone. Also the rate of dissociation of triiodothyronine from nuclei is slower than the rate of loss of binding sites during preincubation in the absence of added hormone. Thus, it appears as if unfilled sites are being lost during the preincubation period. Administration of cycloheximide or actinomycin D, inhibitors of protein and RNA synthesis, respectively, to rats caused a decrease in the amount of triiodothyronine which could be bound in the in vitro binding assay to liver nuclei.", "contents": "Stability of nuclear triiodothyronine binding sites. Rat liver nuclei have recently been shown to possess limited, high affinity binding sites for triiodothyronine, only a fraction of which are believed to be filled in vivo. We have found that preincubation of nuclei in the absence of added triiodothyronine leads to a rapid decrease in binding capacity. This loss of binding sites is considerably faster at 37 C than at 4 C. On the other hand, once binding equilibrium is reached between nuclear bound and free triiodothyronine the level of binding does not change during the time in which a considerable loss of binding had occurred when nuclei were preincubated in the absence of hormone. Also the rate of dissociation of triiodothyronine from nuclei is slower than the rate of loss of binding sites during preincubation in the absence of added hormone. Thus, it appears as if unfilled sites are being lost during the preincubation period. Administration of cycloheximide or actinomycin D, inhibitors of protein and RNA synthesis, respectively, to rats caused a decrease in the amount of triiodothyronine which could be bound in the in vitro binding assay to liver nuclei."}
{"id": "PMID:195795", "title": "Modification of serum luteinizing hormone and prolactin concentrations by corticotropin and adrenalectomy in ovariectomized rats.", "content": "The effects of ACTH and adrenalectomy (ADX) on serum concentrations of LH and prolactin were examined in ovariectomized (OVX) rats. In the first study ACTH (4 IU) was administered daily for one week. ACTH prevented an increase in serum LH in response to OVX and stimulated serum prolactin. ACTH also reduced serum LH in OVX+ADX rats and increased prolactin concentration. ADX was utilized in the second experiment to enhance secretion of endogenous ACTH. Two weeks after ADX serum prolactin was elevated above intact values. ADX also enhanced serum prolactin in OVX rats to the level found in intact animals. ADX markedly reduced the LH response to OVX but ADX alone had no effect on serum LH concentration. All of these findings indicate that ACTH acts directly to reduce serum LH concentration and to enhance serum prolactin. The influence of adrenal corticoids on serum concentrations of LH and prolactin as reported by other investigators appears to be mediated via their negative feedback effects on ACTH release. Whether ACTH has its action on adenohypophyseal cells or on hypothalamic sites has yet to be determined.", "contents": "Modification of serum luteinizing hormone and prolactin concentrations by corticotropin and adrenalectomy in ovariectomized rats. The effects of ACTH and adrenalectomy (ADX) on serum concentrations of LH and prolactin were examined in ovariectomized (OVX) rats. In the first study ACTH (4 IU) was administered daily for one week. ACTH prevented an increase in serum LH in response to OVX and stimulated serum prolactin. ACTH also reduced serum LH in OVX+ADX rats and increased prolactin concentration. ADX was utilized in the second experiment to enhance secretion of endogenous ACTH. Two weeks after ADX serum prolactin was elevated above intact values. ADX also enhanced serum prolactin in OVX rats to the level found in intact animals. ADX markedly reduced the LH response to OVX but ADX alone had no effect on serum LH concentration. All of these findings indicate that ACTH acts directly to reduce serum LH concentration and to enhance serum prolactin. The influence of adrenal corticoids on serum concentrations of LH and prolactin as reported by other investigators appears to be mediated via their negative feedback effects on ACTH release. Whether ACTH has its action on adenohypophyseal cells or on hypothalamic sites has yet to be determined."}
{"id": "PMID:195797", "title": "Regulation of gonadotropin receptors by luteinizing hormone in granulosa cells.", "content": "In association with luteinization, LH induces a decrease in the content of receptors for FSH and LH and an increase in that for PRL. To elucidate if the mechanism by which LH regulates its own receptors involved occupancy of sites and/or loss of receptors the effects of a luteinizing dose of LH were examined in the preovulatory follicles of immature hypophysectomized rats primed with estradiol and FSH. The measurable LH receptor content declined by 82% 24 h after LH administration. Serum concentration of the hormone declined by 24 h to 1.4% of the concentration measured 2 h after LH administration. Administration of iodinated LH to demonstrate occupancy of sites in vivo, resulted in a decline in the amount of hormone bound in vivo, over a period of time. This decline in occupancy paralleled the decrease in the number of available sites as measured in vitro. Furthermore, a large dose of highly purified hFSH administered in lieu of LH induced luteinization and an associated loss of gonadotropin receptors. These results indicate that luteinizing doses of LH and FSH induce a loss in gonadotropin receptors by mechanisms other than occupancy.", "contents": "Regulation of gonadotropin receptors by luteinizing hormone in granulosa cells. In association with luteinization, LH induces a decrease in the content of receptors for FSH and LH and an increase in that for PRL. To elucidate if the mechanism by which LH regulates its own receptors involved occupancy of sites and/or loss of receptors the effects of a luteinizing dose of LH were examined in the preovulatory follicles of immature hypophysectomized rats primed with estradiol and FSH. The measurable LH receptor content declined by 82% 24 h after LH administration. Serum concentration of the hormone declined by 24 h to 1.4% of the concentration measured 2 h after LH administration. Administration of iodinated LH to demonstrate occupancy of sites in vivo, resulted in a decline in the amount of hormone bound in vivo, over a period of time. This decline in occupancy paralleled the decrease in the number of available sites as measured in vitro. Furthermore, a large dose of highly purified hFSH administered in lieu of LH induced luteinization and an associated loss of gonadotropin receptors. These results indicate that luteinizing doses of LH and FSH induce a loss in gonadotropin receptors by mechanisms other than occupancy."}
{"id": "PMID:195801", "title": "Isolation of highly purified Leydig cells by density gradient centrifugation.", "content": "Purification of specific endocrine cells from mixed populations after dispersion of target tissues is important for detailed analysis of mechanisms of hormone action. A simple method for rapid isolation of endocrine cells with retention of biological integrity, has been developed by centrifugation in density gradients formed with Metrizamide. By this procedure, highly purified Leydig cells retaining morphological and biochemical characteristics were obtained. Such preparations bound 20, 300+/-3, 100 molecules of hCG per cell with affinity of 1.1+/-0.25 X 10(10) M-1. During incubation with hCG, cyclic AMP and testosterone responses of purified Leydig cells were considerably increased, and hCG concentrations as low as 0.2 pM caused activation of cAMP-dependent protein kinase.", "contents": "Isolation of highly purified Leydig cells by density gradient centrifugation. Purification of specific endocrine cells from mixed populations after dispersion of target tissues is important for detailed analysis of mechanisms of hormone action. A simple method for rapid isolation of endocrine cells with retention of biological integrity, has been developed by centrifugation in density gradients formed with Metrizamide. By this procedure, highly purified Leydig cells retaining morphological and biochemical characteristics were obtained. Such preparations bound 20, 300+/-3, 100 molecules of hCG per cell with affinity of 1.1+/-0.25 X 10(10) M-1. During incubation with hCG, cyclic AMP and testosterone responses of purified Leydig cells were considerably increased, and hCG concentrations as low as 0.2 pM caused activation of cAMP-dependent protein kinase."}
{"id": "PMID:195803", "title": "Identification of multiple protein kinases in normal human lymphocytes.", "content": "The protein kinase activity of a 10,000 g supernatant of purified human lymphocytes can be resolved by DEAE-cellulose chromatography into six protein kinase fractions: three of them phosphorylate casein preferentially, and three histones. The same procedure with the corresponding nuclear fraction yields only two casein kinases. All these fractions, except one casein kinase of the cytosol, have been studied with respect to protein and nucleotide specificity, effect of salts and of cyclic nucleotides, sedimentation, etc. The results obtained indicate that the enzyme fractions of the cytosol have distinct characteristics, suggesting that they are different protein kinases, and that the nuclear kinases are similar to the two main casein kinases of the cytosol.", "contents": "Identification of multiple protein kinases in normal human lymphocytes. The protein kinase activity of a 10,000 g supernatant of purified human lymphocytes can be resolved by DEAE-cellulose chromatography into six protein kinase fractions: three of them phosphorylate casein preferentially, and three histones. The same procedure with the corresponding nuclear fraction yields only two casein kinases. All these fractions, except one casein kinase of the cytosol, have been studied with respect to protein and nucleotide specificity, effect of salts and of cyclic nucleotides, sedimentation, etc. The results obtained indicate that the enzyme fractions of the cytosol have distinct characteristics, suggesting that they are different protein kinases, and that the nuclear kinases are similar to the two main casein kinases of the cytosol."}
{"id": "PMID:195804", "title": "Characteristics of modulators and substrates binding to rat liver adenylate kinase.", "content": "The binding of adenine nucleotides to liver adenylate kinase was dependent on Mg2+ ions. Citric acid enhanced the binding of all metal-chelated radioactive nucleotides and indicated two observable binding sites for Mg3H-ADP and Mg3-ATP and one-half binding site for Mg3H-AMP. Two binding sites of Mg3H-ADP and one binding site for Mg3H-ATP were also observed in the absence of citric acid. Stoichiometric binding of 14C-citric acid to liver adenylate kinase varied with additions of different nucleotides. AMP prevented whereas ADP and ATP enhanced the binding of 14C-citric acid.", "contents": "Characteristics of modulators and substrates binding to rat liver adenylate kinase. The binding of adenine nucleotides to liver adenylate kinase was dependent on Mg2+ ions. Citric acid enhanced the binding of all metal-chelated radioactive nucleotides and indicated two observable binding sites for Mg3H-ADP and Mg3-ATP and one-half binding site for Mg3H-AMP. Two binding sites of Mg3H-ADP and one binding site for Mg3H-ATP were also observed in the absence of citric acid. Stoichiometric binding of 14C-citric acid to liver adenylate kinase varied with additions of different nucleotides. AMP prevented whereas ADP and ATP enhanced the binding of 14C-citric acid."}
{"id": "PMID:195805", "title": "New protein reagents. N-(4-Chloromercuriphenyl)-4-chloro-3,5-dinitrobenzamide and its use as a probe of the quaternary structure of yeast alcohol dehydrogenase.", "content": "The new bifunctional reagent, N-(4-chloromercuriphenyl)-4-chloro-3,5-dinitrobenzamide (I) was used to investigate the quaternary structure of yeast alcohol dehydrogenase. The four essential - SH groups of the enzyme were substituted by the mercuriphenyl moiety of compound I in the course of the reaction of one mole of protein with four moles of the reagent (one molecule of compound I incorporated by yeast alcohol dehydrogenase monomer). In a second step only two of the four chlorodinitrophenyl fragments bound to the protein established intermonomeric cross-links with non-essential - NH2 groups. The resulting dimers could be re-dissociated with mercaptoethanol. This result suggests that the four protomers of the enzyme could be arranged as a dimer of dimers.", "contents": "New protein reagents. N-(4-Chloromercuriphenyl)-4-chloro-3,5-dinitrobenzamide and its use as a probe of the quaternary structure of yeast alcohol dehydrogenase. The new bifunctional reagent, N-(4-chloromercuriphenyl)-4-chloro-3,5-dinitrobenzamide (I) was used to investigate the quaternary structure of yeast alcohol dehydrogenase. The four essential - SH groups of the enzyme were substituted by the mercuriphenyl moiety of compound I in the course of the reaction of one mole of protein with four moles of the reagent (one molecule of compound I incorporated by yeast alcohol dehydrogenase monomer). In a second step only two of the four chlorodinitrophenyl fragments bound to the protein established intermonomeric cross-links with non-essential - NH2 groups. The resulting dimers could be re-dissociated with mercaptoethanol. This result suggests that the four protomers of the enzyme could be arranged as a dimer of dimers."}
{"id": "PMID:195807", "title": "Proteolysis of L-(+)-lactate cytochrome c oxidoreductase (cytochrome b2) extracted from Saccharomyces cerevisiae and Hansenula anomala yeasts.", "content": "The L-(+)-Lactate:cytochrome c oxidoreductase or cytochrome b2 from the yeasts Saccharomyces cerevisiae and Hansenula anomala were partially hydrolysed in various concentrations of trypsin. Conditions were found which allowed the isolation from the Hansenula enzyme of a 140 000 +/- 10 000-dalton flavoprotein. The prosthetic flavin groups were still reducible by substrate (spectroscopic evidence) but the flavoprotein was unable to form a complex with cytochrome c, the physiological acceptor in the enzymatic reaction. No such flavoprotein units could be found during proteolysis of the Saccharomyces enzyme. The heme prosthetic group of the Hansenula enzyme remained bound to a 15 500 +/- 1000-dalton protein unit which was larger than, but very similar to, the well known 'cytochrome b2 core' of the Saccharomyces enzyme. Moreover, the degradation of different enzyme samples by contaminated proteases allowed the isolation of a particular form of Hansenula enzyme: each tetramer had, on the mean, four bound flavins and only two heme groups. These molecules completely retained their ability to form a complex with cytochrome c.", "contents": "Proteolysis of L-(+)-lactate cytochrome c oxidoreductase (cytochrome b2) extracted from Saccharomyces cerevisiae and Hansenula anomala yeasts. The L-(+)-Lactate:cytochrome c oxidoreductase or cytochrome b2 from the yeasts Saccharomyces cerevisiae and Hansenula anomala were partially hydrolysed in various concentrations of trypsin. Conditions were found which allowed the isolation from the Hansenula enzyme of a 140 000 +/- 10 000-dalton flavoprotein. The prosthetic flavin groups were still reducible by substrate (spectroscopic evidence) but the flavoprotein was unable to form a complex with cytochrome c, the physiological acceptor in the enzymatic reaction. No such flavoprotein units could be found during proteolysis of the Saccharomyces enzyme. The heme prosthetic group of the Hansenula enzyme remained bound to a 15 500 +/- 1000-dalton protein unit which was larger than, but very similar to, the well known 'cytochrome b2 core' of the Saccharomyces enzyme. Moreover, the degradation of different enzyme samples by contaminated proteases allowed the isolation of a particular form of Hansenula enzyme: each tetramer had, on the mean, four bound flavins and only two heme groups. These molecules completely retained their ability to form a complex with cytochrome c."}
{"id": "PMID:195809", "title": "Particle-bound enzymes in the bloodstream form of Trypanosoma brucei.", "content": "We have screened the bloodstream form of Trypanosoma brucei for the presence of enzymes that could serve as markers for the microbodies and the highly repressed mitochondrion of this organism. None of seven known microbody enzymes were detected at all, but glycerol-3-phosphate oxidase, ATPase, isocitrate dehydrogenase, acid phosphatase and part of the hyperoxide dismutase and malate dehydrogenase activities were found to be particle-bound after fractionation of homogenates by differential centrifugation. Part of the ATPase activity was sensitive to oligomycin, an inhibitor of oxidative phosphorylation. This oligomycin-sensitive activity can serve as a specific marker for the mitochondria. More than 80% of the NAD+-linked glycerol-3-phosphate dehydrogenase in T. brucei was found to be particulate and latent. The enzyme could be activated by Triton X-100, by the combined action of sonication and salt, but not by salt alone, and partially by freezing and thawing. We conclude that the NAD+-linked glycerol-3-phosphate dehydrogenase is located inside an organelle.", "contents": "Particle-bound enzymes in the bloodstream form of Trypanosoma brucei. We have screened the bloodstream form of Trypanosoma brucei for the presence of enzymes that could serve as markers for the microbodies and the highly repressed mitochondrion of this organism. None of seven known microbody enzymes were detected at all, but glycerol-3-phosphate oxidase, ATPase, isocitrate dehydrogenase, acid phosphatase and part of the hyperoxide dismutase and malate dehydrogenase activities were found to be particle-bound after fractionation of homogenates by differential centrifugation. Part of the ATPase activity was sensitive to oligomycin, an inhibitor of oxidative phosphorylation. This oligomycin-sensitive activity can serve as a specific marker for the mitochondria. More than 80% of the NAD+-linked glycerol-3-phosphate dehydrogenase in T. brucei was found to be particulate and latent. The enzyme could be activated by Triton X-100, by the combined action of sonication and salt, but not by salt alone, and partially by freezing and thawing. We conclude that the NAD+-linked glycerol-3-phosphate dehydrogenase is located inside an organelle."}
{"id": "PMID:195810", "title": "A comparative analysis of the protein components of plasma membranes isolated from differentiated and undifferentiated mouse neuroblastoma cells in tissue culture.", "content": "The plasma membranes of the cells of mouse neuroblastoma clone NB41A, were isolated without fixation by hardening procedures and were characterised by their enzyme activities and by their morphology in the light and electron microscopes. The membranes were prepared from two kinds of differentiated monolayer cultures; one in which the cells were induced to form long axon-like processes by the addition of N6,O2'-dibutyryladenosine 3':5'-monophosphate to the culture medium, and the other in which the cells were induced to form processes by the addition of 5-bromo-2'-deoxyuridine. The proteins from the solubilised membranes were compared with similar preparation from the membranes of undifferentiated cells, grown in suspension, by sodium dodecylsulphate polyacrylamide gel electrophoresis, using the incorporation of radioactive amino acids and L-fucose into proteins in the cultures to follow the differences in the patterns of polypeptide synthesis and glycosylation of the membrane proteins. The differentiated cells induced with either inducer show an increased incorporation of L-fucose into two distinct components with molecular weights of 60 000 and 70 000. The two types of induced cells differ from each other in that N6,O2'-dibutyryladenosine 3':5'-monophosphate stimulates both glycosylation and protein synthesis, with a relative increase in the low molecular weight proteins, but 5-bromo-2'-deoxyuridine stimulates mostly increased glycosylation of the membrane proteins.", "contents": "A comparative analysis of the protein components of plasma membranes isolated from differentiated and undifferentiated mouse neuroblastoma cells in tissue culture. The plasma membranes of the cells of mouse neuroblastoma clone NB41A, were isolated without fixation by hardening procedures and were characterised by their enzyme activities and by their morphology in the light and electron microscopes. The membranes were prepared from two kinds of differentiated monolayer cultures; one in which the cells were induced to form long axon-like processes by the addition of N6,O2'-dibutyryladenosine 3':5'-monophosphate to the culture medium, and the other in which the cells were induced to form processes by the addition of 5-bromo-2'-deoxyuridine. The proteins from the solubilised membranes were compared with similar preparation from the membranes of undifferentiated cells, grown in suspension, by sodium dodecylsulphate polyacrylamide gel electrophoresis, using the incorporation of radioactive amino acids and L-fucose into proteins in the cultures to follow the differences in the patterns of polypeptide synthesis and glycosylation of the membrane proteins. The differentiated cells induced with either inducer show an increased incorporation of L-fucose into two distinct components with molecular weights of 60 000 and 70 000. The two types of induced cells differ from each other in that N6,O2'-dibutyryladenosine 3':5'-monophosphate stimulates both glycosylation and protein synthesis, with a relative increase in the low molecular weight proteins, but 5-bromo-2'-deoxyuridine stimulates mostly increased glycosylation of the membrane proteins."}
{"id": "PMID:195812", "title": "On the interrelationship of prostaglandin endoperoxide G2 and cyclic nucleotides in platelet function.", "content": "The prostaglandin endoperoxide G2 caused rapid aggregation and relase of ADP and [14C]serotonin in human platelets. Since the presence of the ADP phosphorylating system creatine phosphate/creatine phosphokinase markedly inhibited the aggregation caused by the endoperoxide, this effect seemed to be mediated mainly by ADP, which is instantaneously released by the endoperoxide. The prostaglandin G2 counteracted the increasing effect of prostaglandin E1 on the adenosine 3':5'-monophosphate (cAMP) levels in platelet-rich plasma. This effect of prostaglandin G2 was only observed when ADP was released by the endoperoxide. This finding indicates that the effect of prostaglandin G2 on the cAMP levels in platelet-rich plasma is principally mediated by ADP. The rapid release of ADP by prostaglandin G2 and the time courses for the effects of the endoperoxide and ADP on the level of cAMP give further evidence for this hypothesis. ADP also caused primary aggregation in the presence of indomethacin, and prostaglandin synthesis inhibitors did not influence the decreasing effect of ADP on the cAMP levels. N2,O2-Dibutyrylguanosine 3':5'-monophosphate did not influence the aggregation and release-reaction caused by ADP and no changes of the cGMP levels were observed after addition of prostaglandin G2.", "contents": "On the interrelationship of prostaglandin endoperoxide G2 and cyclic nucleotides in platelet function. The prostaglandin endoperoxide G2 caused rapid aggregation and relase of ADP and [14C]serotonin in human platelets. Since the presence of the ADP phosphorylating system creatine phosphate/creatine phosphokinase markedly inhibited the aggregation caused by the endoperoxide, this effect seemed to be mediated mainly by ADP, which is instantaneously released by the endoperoxide. The prostaglandin G2 counteracted the increasing effect of prostaglandin E1 on the adenosine 3':5'-monophosphate (cAMP) levels in platelet-rich plasma. This effect of prostaglandin G2 was only observed when ADP was released by the endoperoxide. This finding indicates that the effect of prostaglandin G2 on the cAMP levels in platelet-rich plasma is principally mediated by ADP. The rapid release of ADP by prostaglandin G2 and the time courses for the effects of the endoperoxide and ADP on the level of cAMP give further evidence for this hypothesis. ADP also caused primary aggregation in the presence of indomethacin, and prostaglandin synthesis inhibitors did not influence the decreasing effect of ADP on the cAMP levels. N2,O2-Dibutyrylguanosine 3':5'-monophosphate did not influence the aggregation and release-reaction caused by ADP and no changes of the cGMP levels were observed after addition of prostaglandin G2."}
{"id": "PMID:195814", "title": "Activity of protein kinase dependent on adenosine 3':5'-monophosphate and of its thermostable protein inhibitor in rat hepatoma (HTC) cells. Unlikely role in the permissive action of glucocorticoids.", "content": "Normal expression of a variety of hormonal effects which depend on cyclic AMP (adenosine 3':5'-monophosphate) requires the presence of glucocorticoids. Our hypothesis was that glucocorticoids control directly or indirectly the activity of cyclic-AMP-dependent protein kinase. This has been investigated in cultured hepatoma (HTC) cells in which N6,O2'-dibutyryladenosine 3':5'-monophosphate increases the activity of tyrosine transaminase only after glucocorticoid treatment. In these cells, we have determined the concentration and half-life of protein kinase, the sensitivity of this enzyme in vitro to cyclic AMP and to its thermostable protein inhibitor, the state of dissociation of protein kinase holoenzyme in vivo and its sensitivity, in the intact cell, to dibutyryladenosine 3':5'-monophosphate and to the inhibitor diamide, and we have also determined the concentration of endogenous thermostable protein inhibitor of protein kinase. None of these parameters were influenced by glucocorticoids under conditions where these hormones stimulate the activity of tyrosine transaminase and restore sensitivity to dibutyryladenosine 3':5'-monophosphate. It is concluded that the permissive action of glucocorticoids probably results from a control of cyclic-AMP-dependent processes exerted at a level beyond the protein kinase system.", "contents": "Activity of protein kinase dependent on adenosine 3':5'-monophosphate and of its thermostable protein inhibitor in rat hepatoma (HTC) cells. Unlikely role in the permissive action of glucocorticoids. Normal expression of a variety of hormonal effects which depend on cyclic AMP (adenosine 3':5'-monophosphate) requires the presence of glucocorticoids. Our hypothesis was that glucocorticoids control directly or indirectly the activity of cyclic-AMP-dependent protein kinase. This has been investigated in cultured hepatoma (HTC) cells in which N6,O2'-dibutyryladenosine 3':5'-monophosphate increases the activity of tyrosine transaminase only after glucocorticoid treatment. In these cells, we have determined the concentration and half-life of protein kinase, the sensitivity of this enzyme in vitro to cyclic AMP and to its thermostable protein inhibitor, the state of dissociation of protein kinase holoenzyme in vivo and its sensitivity, in the intact cell, to dibutyryladenosine 3':5'-monophosphate and to the inhibitor diamide, and we have also determined the concentration of endogenous thermostable protein inhibitor of protein kinase. None of these parameters were influenced by glucocorticoids under conditions where these hormones stimulate the activity of tyrosine transaminase and restore sensitivity to dibutyryladenosine 3':5'-monophosphate. It is concluded that the permissive action of glucocorticoids probably results from a control of cyclic-AMP-dependent processes exerted at a level beyond the protein kinase system."}
{"id": "PMID:195815", "title": "The major polypeptides of the murine-mammary-tumor virus isolated by plant-lectin affinity chromatography.", "content": "Solubilized polypeptides of the murine mammary tumor virus (MuMT virus) were chromatographed on a column of immobilised concanavalin A. The unbound viral material was rechromatographed on phosphocellulose, resulting in the isolation of the major proteins with a molecular weight of 28000 (p28) and 12000 (p12) respectively. The adsorbed glycopolypeptides after elution with methyl alpha-D-mannopyranoside were subjected to gel filtration. The major glycoprotein with a molecular weight of 52000 (gp52) was obtained in an almost pure form. However, a considerable part of gp52 elutes together with a glycoprotein with a molecular weight of 36000 (gp36), suggesting that in addition to the free form of gp52 a complex exists of gp52 plus gp36.", "contents": "The major polypeptides of the murine-mammary-tumor virus isolated by plant-lectin affinity chromatography. Solubilized polypeptides of the murine mammary tumor virus (MuMT virus) were chromatographed on a column of immobilised concanavalin A. The unbound viral material was rechromatographed on phosphocellulose, resulting in the isolation of the major proteins with a molecular weight of 28000 (p28) and 12000 (p12) respectively. The adsorbed glycopolypeptides after elution with methyl alpha-D-mannopyranoside were subjected to gel filtration. The major glycoprotein with a molecular weight of 52000 (gp52) was obtained in an almost pure form. However, a considerable part of gp52 elutes together with a glycoprotein with a molecular weight of 36000 (gp36), suggesting that in addition to the free form of gp52 a complex exists of gp52 plus gp36."}
{"id": "PMID:195816", "title": "Analysis of the relA gene product of Escherichia coli.", "content": "The relA gene product, ATP: GTP 3'-pyrophosphotransferase (stringent factor) has been isolated in homogeneous form from an Escherichia coli strain polyploid for this gene at a yield of 1 mg/100 g cells and at a specific activity in a ribosome-activated assay at 37 degrees C of 120 mumol guanosine pentaphosphate formed min-1 mg protein-1. The specific activity in a methanol-activated assay at 25 degrees C was found to be 4 mumol guanosine pentaphosphate formed min-1 mg protein-1. These values are about 100 times higher than reported by others. Our further studies of this enzyme led to the following results. Antibodies raised against this enzyme inhibit the ribosome-activated synthesis of guanosine tetraphosphate and pentaphosphate but have no effect on the much slower synthesis, detected in the absence of ribosomes. The amount of stringent factor in the relA+ strain CP78 is estimated to about 1 copy per 200 ribosomes. The amount of antibody-binding material in CP79 (relA) is at least 5 times lower.", "contents": "Analysis of the relA gene product of Escherichia coli. The relA gene product, ATP: GTP 3'-pyrophosphotransferase (stringent factor) has been isolated in homogeneous form from an Escherichia coli strain polyploid for this gene at a yield of 1 mg/100 g cells and at a specific activity in a ribosome-activated assay at 37 degrees C of 120 mumol guanosine pentaphosphate formed min-1 mg protein-1. The specific activity in a methanol-activated assay at 25 degrees C was found to be 4 mumol guanosine pentaphosphate formed min-1 mg protein-1. These values are about 100 times higher than reported by others. Our further studies of this enzyme led to the following results. Antibodies raised against this enzyme inhibit the ribosome-activated synthesis of guanosine tetraphosphate and pentaphosphate but have no effect on the much slower synthesis, detected in the absence of ribosomes. The amount of stringent factor in the relA+ strain CP78 is estimated to about 1 copy per 200 ribosomes. The amount of antibody-binding material in CP79 (relA) is at least 5 times lower."}
{"id": "PMID:195817", "title": "Ultrastructural features in a case of ureteric malakoplakia.", "content": "A case of urinary malakoplakia involving both ureters and the bladder is presented. Ultrastructural data relating to the ureteric lesion are illustrated. Pale, dark and intermediate cells were involved in the pathological process. Features common and specific for these three types of cell are described. Dark cells are thought to be of a histiocytic nature, while the others are of either histiocyte or urothelial origin. Cytoplasmic inclusions were abundant in all three types in the form of single-or multicentred multilamellar bodies. It was not clear whether these were the product of secretion or phagocytosis. Michaelis-Gutmann bodies, on the other hand, were found to be due to the deposition of needle-like crystals inside pre-existing multicentred multilamellar bodies. Pathogens could not be demonstrated for certain. It is felt, therefore, that the aetiology of malakoplakia must be considered as debatable. Biochemical and immunological research directed to the detection of a possible enzyme deficiency is suggested, along with further ultrastructural investigation of the histogenesis of the pale and intermediate cells.", "contents": "Ultrastructural features in a case of ureteric malakoplakia. A case of urinary malakoplakia involving both ureters and the bladder is presented. Ultrastructural data relating to the ureteric lesion are illustrated. Pale, dark and intermediate cells were involved in the pathological process. Features common and specific for these three types of cell are described. Dark cells are thought to be of a histiocytic nature, while the others are of either histiocyte or urothelial origin. Cytoplasmic inclusions were abundant in all three types in the form of single-or multicentred multilamellar bodies. It was not clear whether these were the product of secretion or phagocytosis. Michaelis-Gutmann bodies, on the other hand, were found to be due to the deposition of needle-like crystals inside pre-existing multicentred multilamellar bodies. Pathogens could not be demonstrated for certain. It is felt, therefore, that the aetiology of malakoplakia must be considered as debatable. Biochemical and immunological research directed to the detection of a possible enzyme deficiency is suggested, along with further ultrastructural investigation of the histogenesis of the pale and intermediate cells."}
{"id": "PMID:195820", "title": "Post-nephrectomy changes in adrenal angiotensin II receptors in the rat; influence of exogenous angiotensin and a competitive inhibitor.", "content": "3H-angiotensin binding sites have been studied in a particulate fraction prepared from rat adrenal glands. This binding is rapid and reversible, of high affinity (KD29 degrees C = 3-5 X 10(-9) M) and with demonstrable specificity for the angiotensin II octapeptide. The number of binding sites varies with endogenous angiotensin levels: nephrectomy is followed by an increase in number of binding sites. This increase can be prevented by chronic angiotensin II administration and, to a lesser extent, by administration of Sar1,Ala8-angiotensin II, a competitive antagonist of the hormone. No variation in the equilibrium dissociation constant accompanied these changes in binding capacity. The post-nephrectomy increase in capacity is time-dependent, with a lag period of 24-40 h. The observed changes in receptor concentration do not appear explicable on the basis of receptor occupancy. Accordingly, angiotensin II receptors in the rat adrenal appear to be dependent on circulating angiotensin levels as previously reported for rat uterus.", "contents": "Post-nephrectomy changes in adrenal angiotensin II receptors in the rat; influence of exogenous angiotensin and a competitive inhibitor. 3H-angiotensin binding sites have been studied in a particulate fraction prepared from rat adrenal glands. This binding is rapid and reversible, of high affinity (KD29 degrees C = 3-5 X 10(-9) M) and with demonstrable specificity for the angiotensin II octapeptide. The number of binding sites varies with endogenous angiotensin levels: nephrectomy is followed by an increase in number of binding sites. This increase can be prevented by chronic angiotensin II administration and, to a lesser extent, by administration of Sar1,Ala8-angiotensin II, a competitive antagonist of the hormone. No variation in the equilibrium dissociation constant accompanied these changes in binding capacity. The post-nephrectomy increase in capacity is time-dependent, with a lag period of 24-40 h. The observed changes in receptor concentration do not appear explicable on the basis of receptor occupancy. Accordingly, angiotensin II receptors in the rat adrenal appear to be dependent on circulating angiotensin levels as previously reported for rat uterus."}
{"id": "PMID:195822", "title": "The mechanism of action of two bradykinin-potentiating peptides on isolated smooth muscle.", "content": "Bradykinin-induced contractions in the guinea-pig ileum were potentiated by the peptides A-VI-5 (Val-Glu-Ser-Ser-Lys) and BPP5a (Pyr-Lys-Trp-Ala-Pro), while the contractions induced by other agonists were not affected. Neither peptide added alone caused any response. Previous addition of the peptides shortened the latent period following the addition of bradykinin to a value corresponding to the contraction height with an equivalent dose of bradykinin added alone. Bradykinin in contact with a piece of ileum was inactivated at a relatively slow rate. This inactivation was not inhibited by either A-VI-5 or BPP5a in doses causing potentiation. Suppression of the cholinergic activity by cooling, atropine, morphine or tetrodotoxin did not influence the potentiating activity. Addition of the peptides at the moment a submaximal contraction due to bradykinin had been fully established, increased the contraction height within seconds. The two peptides caused a parallel shift to the left of the dose-effect curve of bradykinin, whereas the maximum bradykinin effect remained unchanged. It is concluded that sensitization of bradykinin receptors due to an increased affinity of the receptor for bradykinin is the hypothesis which best fits the experimental findings.", "contents": "The mechanism of action of two bradykinin-potentiating peptides on isolated smooth muscle. Bradykinin-induced contractions in the guinea-pig ileum were potentiated by the peptides A-VI-5 (Val-Glu-Ser-Ser-Lys) and BPP5a (Pyr-Lys-Trp-Ala-Pro), while the contractions induced by other agonists were not affected. Neither peptide added alone caused any response. Previous addition of the peptides shortened the latent period following the addition of bradykinin to a value corresponding to the contraction height with an equivalent dose of bradykinin added alone. Bradykinin in contact with a piece of ileum was inactivated at a relatively slow rate. This inactivation was not inhibited by either A-VI-5 or BPP5a in doses causing potentiation. Suppression of the cholinergic activity by cooling, atropine, morphine or tetrodotoxin did not influence the potentiating activity. Addition of the peptides at the moment a submaximal contraction due to bradykinin had been fully established, increased the contraction height within seconds. The two peptides caused a parallel shift to the left of the dose-effect curve of bradykinin, whereas the maximum bradykinin effect remained unchanged. It is concluded that sensitization of bradykinin receptors due to an increased affinity of the receptor for bradykinin is the hypothesis which best fits the experimental findings."}
{"id": "PMID:195824", "title": "A study of binocular convergence in cat visual cortex neurons.", "content": "The average latency of cortical neuronal responses to electrical optic nerve (ON) stimulation was 3.0 +/- 0.7 s.d. msec. No significant difference between latencies to ipsi- and contralateral ON stimulation was found. Binocularly excitable cells showed almost equal response latencies to stimulation of both nerves. The average latency of subcortically recorded geniculo-cortical fibers was 0.3 msec less, but showed the same variance as that of cortical cells, suggesting that in all cases direct monosynaptic excitation of cortical cells by fibers of either ocularity is possible. Classes of ocular dominance based on electrical stimulation were positively, but not 100% correlated with classes of ocular dominance to visual stimulation. An anatomical study revealed that in cat terminals of geniculo-cortical projection are segregated to a lesser degree into ocularity stripes than in monkey. Direct monosynaptic excitation of cells by fibers of either ocularity which was found physiologically would also on these grounds appear possible for all cells.", "contents": "A study of binocular convergence in cat visual cortex neurons. The average latency of cortical neuronal responses to electrical optic nerve (ON) stimulation was 3.0 +/- 0.7 s.d. msec. No significant difference between latencies to ipsi- and contralateral ON stimulation was found. Binocularly excitable cells showed almost equal response latencies to stimulation of both nerves. The average latency of subcortically recorded geniculo-cortical fibers was 0.3 msec less, but showed the same variance as that of cortical cells, suggesting that in all cases direct monosynaptic excitation of cortical cells by fibers of either ocularity is possible. Classes of ocular dominance based on electrical stimulation were positively, but not 100% correlated with classes of ocular dominance to visual stimulation. An anatomical study revealed that in cat terminals of geniculo-cortical projection are segregated to a lesser degree into ocularity stripes than in monkey. Direct monosynaptic excitation of cells by fibers of either ocularity which was found physiologically would also on these grounds appear possible for all cells."}
{"id": "PMID:195825", "title": "Maturation of evoked climbing fiber input to rat cerebellar purkinje cells (I.).", "content": "An analysis of evoked responses of Purkinje cells in developing rat cerebellum to climbing fiber input was conducted to determine which identifying properties of this afferent system are established early in development and which specific features mature with age. Rat pups at various ages were anesthetized with 0.5% halothane and unit recordings made with glass micropipettes. By the third postnatal day, electrical stimulation of the sensorimotor cortex and limbs at low stimulation rates (less than 1/sec) could elicit distinct burst responses appearing at long latencies (180 msec), indicating that pathways of both ascending and descending climbing fiber systems are intact early in cerebellar cortical development. A distinctive feature maturing over the first 1-1.5 weeks was the characteristic of the all-or-none burst response since before about day 11 the interspike interval, amount of inactivation, and number of spikes in evoked burst responses all varied from stimulation to stimulation. Mean latencies decreased from 180 msec at dat 3 to 50 msec by day 10, but did not achieve the adult value of 20 msec until the fourth week. Typically, climbing fiber responses could only follow at stimulation rates of less than 0.2/sec at day 3, but by day 12 could follow up to 10/sec, which is the same as in the adult. The data indicate that the climbing fiber system establishes connectivity from diverse sources and exhibits identifying characteristics similar to the adult early in cerebellar development. Most aspects of the maturation of transmission can be explained if there were a decrease in the time scale of function of the synapses involved, mainly those in the inferior olive.", "contents": "Maturation of evoked climbing fiber input to rat cerebellar purkinje cells (I.). An analysis of evoked responses of Purkinje cells in developing rat cerebellum to climbing fiber input was conducted to determine which identifying properties of this afferent system are established early in development and which specific features mature with age. Rat pups at various ages were anesthetized with 0.5% halothane and unit recordings made with glass micropipettes. By the third postnatal day, electrical stimulation of the sensorimotor cortex and limbs at low stimulation rates (less than 1/sec) could elicit distinct burst responses appearing at long latencies (180 msec), indicating that pathways of both ascending and descending climbing fiber systems are intact early in cerebellar cortical development. A distinctive feature maturing over the first 1-1.5 weeks was the characteristic of the all-or-none burst response since before about day 11 the interspike interval, amount of inactivation, and number of spikes in evoked burst responses all varied from stimulation to stimulation. Mean latencies decreased from 180 msec at dat 3 to 50 msec by day 10, but did not achieve the adult value of 20 msec until the fourth week. Typically, climbing fiber responses could only follow at stimulation rates of less than 0.2/sec at day 3, but by day 12 could follow up to 10/sec, which is the same as in the adult. The data indicate that the climbing fiber system establishes connectivity from diverse sources and exhibits identifying characteristics similar to the adult early in cerebellar development. Most aspects of the maturation of transmission can be explained if there were a decrease in the time scale of function of the synapses involved, mainly those in the inferior olive."}
{"id": "PMID:195826", "title": "The buoyant density of synaptic plasma membranes from the cerebral cortex of neonatal rats.", "content": "A fraction enriched in synaptic plasma membranes was prepared from neonatal (5-6 day old) rat cerebral cortex. The procedure was based on a method used to prepare synaptic plasma membranes from adult cerebral cortex. Critical steps were monitored by electron microscopy. Synaptic plasma membranes from neonatal cerebral cortex sedimented as a broad peak between 0.9 M and 1.1 M sucrose. In contrast, the majority of adult synaptic plasma membranes have been reported to sediment to 1.2 M sucorose. The activities of various enzyme markers were determined in subfractions of neonatal preparations in order to estimate contamination. The specific activities of these markers indicated substantial contamination of the neonatal synaptic plasma membrane fractions by microsomes and glia.", "contents": "The buoyant density of synaptic plasma membranes from the cerebral cortex of neonatal rats. A fraction enriched in synaptic plasma membranes was prepared from neonatal (5-6 day old) rat cerebral cortex. The procedure was based on a method used to prepare synaptic plasma membranes from adult cerebral cortex. Critical steps were monitored by electron microscopy. Synaptic plasma membranes from neonatal cerebral cortex sedimented as a broad peak between 0.9 M and 1.1 M sucrose. In contrast, the majority of adult synaptic plasma membranes have been reported to sediment to 1.2 M sucorose. The activities of various enzyme markers were determined in subfractions of neonatal preparations in order to estimate contamination. The specific activities of these markers indicated substantial contamination of the neonatal synaptic plasma membrane fractions by microsomes and glia."}
{"id": "PMID:195827", "title": "Evidence that catecholamines are not the afferent transmitter in the cochlea.", "content": "Beta-receptor blocking agents (practolol, propranolol) and alpha-receptor blocking agents (phenoxybenzamine, phentolamine), when applied intracochlearly do not eliminate the afferetn discharges or compound action potential of the cochlear nerve. Under the assumption that the drugs used reach the synaptic site, it is therefore concluded that these drugs do not interfere with afferent synaptic transmission. Phentolamine,, however, has a toxic effect upon the cochlea independent from the synaptic process. Local application of catecholamines does not increase spontaneous activity of single fibres of the cochlear nerve. These findings show that catecholamines are not likely to be the afferent transmitter.", "contents": "Evidence that catecholamines are not the afferent transmitter in the cochlea. Beta-receptor blocking agents (practolol, propranolol) and alpha-receptor blocking agents (phenoxybenzamine, phentolamine), when applied intracochlearly do not eliminate the afferetn discharges or compound action potential of the cochlear nerve. Under the assumption that the drugs used reach the synaptic site, it is therefore concluded that these drugs do not interfere with afferent synaptic transmission. Phentolamine,, however, has a toxic effect upon the cochlea independent from the synaptic process. Local application of catecholamines does not increase spontaneous activity of single fibres of the cochlear nerve. These findings show that catecholamines are not likely to be the afferent transmitter."}
{"id": "PMID:195835", "title": "[Pharmacological analysis of monoaminergic effects of the amygdaloid complex on the food-procuring conditioned reaction of rats].", "content": "The produced by microinjections of dopamine, norepinephrine, serotonin and glutamic acid into the dorsomedial divisions of the tonsil on the food-procuring conditioned reaction of rats was studied. All of the studied substances were found to lengthen the latent time of the conditioned food reaction, the number of food-procuring movements and the scope of the reflex increasing under the effect of dopamine and serotonin, but diminishing following introduction of norepinephrine and glutamic acid. The dopamine effects materialize through the medium of the tonsil neuron receptors, which are sensitive of haloperidol or chloropromazine, and those serotnin--through D-serotonin-sensitive neuron system structures of the amygdaloid complex. The inhibitory effects of norepinephrine are not of an elective nature, for they correlate with the depression of the spontaneous motor activity of the rats. The modulating influence of glutamic acid on the food-procuring conditioned reflex reaction of the rats is not associated with the action on the dopamine, or serotonin-reactive neuron systems of the dorso-medial tonsil.", "contents": "[Pharmacological analysis of monoaminergic effects of the amygdaloid complex on the food-procuring conditioned reaction of rats]. The produced by microinjections of dopamine, norepinephrine, serotonin and glutamic acid into the dorsomedial divisions of the tonsil on the food-procuring conditioned reaction of rats was studied. All of the studied substances were found to lengthen the latent time of the conditioned food reaction, the number of food-procuring movements and the scope of the reflex increasing under the effect of dopamine and serotonin, but diminishing following introduction of norepinephrine and glutamic acid. The dopamine effects materialize through the medium of the tonsil neuron receptors, which are sensitive of haloperidol or chloropromazine, and those serotnin--through D-serotonin-sensitive neuron system structures of the amygdaloid complex. The inhibitory effects of norepinephrine are not of an elective nature, for they correlate with the depression of the spontaneous motor activity of the rats. The modulating influence of glutamic acid on the food-procuring conditioned reflex reaction of the rats is not associated with the action on the dopamine, or serotonin-reactive neuron systems of the dorso-medial tonsil."}
{"id": "PMID:195836", "title": "[Effect of ethyron on carbohydrate metabolism in the myocardium].", "content": "Tests staged on rats showed the hypertensive drug ethyron (ethylisothiuronium) to intensify the activity of the oxidative system and pentose cycle in the myocardium, to increase the pyruvate content, raise the redox potential of the lactate-pyruvate potential, to reduce the amount of lactate, heighten the activity of the lactate, malate dehydrogenases, glucose-6-phosphate and cytochrome-c-oxydase. In an isolated spontaneously contracting atrium ethyron abolished the suppressing effect of carbohydrate metabolism inhibitors (sodium fluoride and copper sulphate) on the intensity and frequency of contractions.", "contents": "[Effect of ethyron on carbohydrate metabolism in the myocardium]. Tests staged on rats showed the hypertensive drug ethyron (ethylisothiuronium) to intensify the activity of the oxidative system and pentose cycle in the myocardium, to increase the pyruvate content, raise the redox potential of the lactate-pyruvate potential, to reduce the amount of lactate, heighten the activity of the lactate, malate dehydrogenases, glucose-6-phosphate and cytochrome-c-oxydase. In an isolated spontaneously contracting atrium ethyron abolished the suppressing effect of carbohydrate metabolism inhibitors (sodium fluoride and copper sulphate) on the intensity and frequency of contractions."}
{"id": "PMID:195837", "title": "[Functional-morphological state of the digestive organs after administration of dianabol].", "content": "In tests set up on rats the effect of methandrostenolone on the external secretion of the liver, fermentative activity of the pancreatic tissue and histological and hisochemical findings subsequent to an investigation of internal organs were studied. Introduction of methandrostenolone led to changes in bilification and to a reduced concentration basic components of the bile, to a distinctly pronounced rise in the level of the trypsin inhibitor and to a depressed activity of trypsin in the pancreatic tissue. It also resulted in a change of histochemical and fermentative indices in the tissue of the liver, spleen and other organs.", "contents": "[Functional-morphological state of the digestive organs after administration of dianabol]. In tests set up on rats the effect of methandrostenolone on the external secretion of the liver, fermentative activity of the pancreatic tissue and histological and hisochemical findings subsequent to an investigation of internal organs were studied. Introduction of methandrostenolone led to changes in bilification and to a reduced concentration basic components of the bile, to a distinctly pronounced rise in the level of the trypsin inhibitor and to a depressed activity of trypsin in the pancreatic tissue. It also resulted in a change of histochemical and fermentative indices in the tissue of the liver, spleen and other organs."}
{"id": "PMID:195846", "title": "[Mechanism of action of catecholamines on sodium transport in sections of rat renal cortex].", "content": "Stimulation of renal beta-adrenoreceptors increased passive accumulation of sodium and water contents in cells of renal sections incubated in non-oxygenated medium without potassium and glucose but had no effect on the passive loss of potassiuna. During incibation of sodium loaded sections in oxygenated medium with potassium and glucose, stimulation of beta-adrenoreceptors increased excertion of sodium from the sections, and accumulation of potassium, which was followed by reducing of intracellular water. Activation of beta-adrenoreceptors during action of catecholamines seems to elicit an increased passive inflow of sodium into the cells of renal channels and to activate the ionic pump pumping away sodium in exchange for potassium.", "contents": "[Mechanism of action of catecholamines on sodium transport in sections of rat renal cortex]. Stimulation of renal beta-adrenoreceptors increased passive accumulation of sodium and water contents in cells of renal sections incubated in non-oxygenated medium without potassium and glucose but had no effect on the passive loss of potassiuna. During incibation of sodium loaded sections in oxygenated medium with potassium and glucose, stimulation of beta-adrenoreceptors increased excertion of sodium from the sections, and accumulation of potassium, which was followed by reducing of intracellular water. Activation of beta-adrenoreceptors during action of catecholamines seems to elicit an increased passive inflow of sodium into the cells of renal channels and to activate the ionic pump pumping away sodium in exchange for potassium."}
{"id": "PMID:195847", "title": "[Excitatory postsynaptic potentials in the lumbar motor neurons of frogs induced by stimulation of muscle and cutaneous nerves].", "content": "The postsynaptic effects evoked in lumbar motoneurons by stimulation of different muscle and cutaneous nerves of hindlimbs were studied by means of intracellular recording in the frog isolated spinal cord. The data obtained confirm presence of monosynaptic connections between primary afferents and spinal motoneurons. Monosynaptic EPSPs were shown to be due to low threshold muscle afferent volleys in homonymous nerves and did not generate spike discharges. The mean amplitude of monosynaptic EPSPs was 1.1 +/- 0.12 mV, time-to-peak 1.76 +/- 0.16 msec, time constant of decay from 6.0 to 15.0 msec. EPSPs with no synaptic delay were recorded in some motoneurons which suggest existence of an electrical mechanism of transmission.", "contents": "[Excitatory postsynaptic potentials in the lumbar motor neurons of frogs induced by stimulation of muscle and cutaneous nerves]. The postsynaptic effects evoked in lumbar motoneurons by stimulation of different muscle and cutaneous nerves of hindlimbs were studied by means of intracellular recording in the frog isolated spinal cord. The data obtained confirm presence of monosynaptic connections between primary afferents and spinal motoneurons. Monosynaptic EPSPs were shown to be due to low threshold muscle afferent volleys in homonymous nerves and did not generate spike discharges. The mean amplitude of monosynaptic EPSPs was 1.1 +/- 0.12 mV, time-to-peak 1.76 +/- 0.16 msec, time constant of decay from 6.0 to 15.0 msec. EPSPs with no synaptic delay were recorded in some motoneurons which suggest existence of an electrical mechanism of transmission."}
{"id": "PMID:195849", "title": "Changes in radiosensitivity induced by cyclic nucleotides and chemical radioprotection.", "content": "Cyclic AMP has a radioprotective effect and its aministration results in a significant increase in LD50/30 values in Chinese hamsters. The efficiency of these radioprotective effects is comparable to that of such radioprotective compounds as AET and cystamine + mexamine. Cyclic GMP is responsible for significant radiosensitizing effects. Changes in radiosensitivity after administration of cyclic nucleotides are both immediate and delayed and correlate closely with dose and time of administration.", "contents": "Changes in radiosensitivity induced by cyclic nucleotides and chemical radioprotection. Cyclic AMP has a radioprotective effect and its aministration results in a significant increase in LD50/30 values in Chinese hamsters. The efficiency of these radioprotective effects is comparable to that of such radioprotective compounds as AET and cystamine + mexamine. Cyclic GMP is responsible for significant radiosensitizing effects. Changes in radiosensitivity after administration of cyclic nucleotides are both immediate and delayed and correlate closely with dose and time of administration."}
{"id": "PMID:195852", "title": "hCG suppression of LH receptors and responsiveness of testicular tissue to hCG.", "content": "A single injection of 75 IU of human chorionic gonadotropin (hCG) into adult male rats caused a dramatic reduction in the concentration of membrane receptors for luteinizing hormone (LH) in the testis. The mean receptor level reached a nadir which was 5--10% of that in the control testes, 3 days after the injection, after which it gradually returned toward normal. This cannot be due to increased competition caused by the injected hCG since no decrease was observed at a time when the circulating levels of hCG were at a maximum (2--24 h after injection). Furthermore, at a time when receptor levels had been maximally reduced, circulating hCG was at or below the level of detection. Reduction in the number of LH binding sites in the testis was associated with a decreased responsiveness of the testicular tissue to hCG as measured by hCG-stimulated testosterone production in vitro. This inhibitory effect of large quantities of LH on its own receptor is suggested as a possible explantation for the previously observed low concentrations of LH receptor in the testis of the testicular feminized male (tfm) rat. This syndrome is characterized by high endogenous levels of plasma LH (Sherins et al., 1971).", "contents": "hCG suppression of LH receptors and responsiveness of testicular tissue to hCG. A single injection of 75 IU of human chorionic gonadotropin (hCG) into adult male rats caused a dramatic reduction in the concentration of membrane receptors for luteinizing hormone (LH) in the testis. The mean receptor level reached a nadir which was 5--10% of that in the control testes, 3 days after the injection, after which it gradually returned toward normal. This cannot be due to increased competition caused by the injected hCG since no decrease was observed at a time when the circulating levels of hCG were at a maximum (2--24 h after injection). Furthermore, at a time when receptor levels had been maximally reduced, circulating hCG was at or below the level of detection. Reduction in the number of LH binding sites in the testis was associated with a decreased responsiveness of the testicular tissue to hCG as measured by hCG-stimulated testosterone production in vitro. This inhibitory effect of large quantities of LH on its own receptor is suggested as a possible explantation for the previously observed low concentrations of LH receptor in the testis of the testicular feminized male (tfm) rat. This syndrome is characterized by high endogenous levels of plasma LH (Sherins et al., 1971)."}
{"id": "PMID:195857", "title": "Pancreatic perinuclear inclusions in diabetes mellitus and other diseases.", "content": "Unusual perinuclear inclusions in pancreatic duct cells were observed by electron microscopy in 23 diabetic pancreases, in nine pancreases with islet hyperplasia, and in 10 of 27 pancreases without islet pathology. The origin and significance of the perinuclear inclusions could not be determined, but it is suggested that they may be of viral origin or may represent a cellular response to an unknown stimulus.", "contents": "Pancreatic perinuclear inclusions in diabetes mellitus and other diseases. Unusual perinuclear inclusions in pancreatic duct cells were observed by electron microscopy in 23 diabetic pancreases, in nine pancreases with islet hyperplasia, and in 10 of 27 pancreases without islet pathology. The origin and significance of the perinuclear inclusions could not be determined, but it is suggested that they may be of viral origin or may represent a cellular response to an unknown stimulus."}
{"id": "PMID:195860", "title": "[Antibodies against the cytomegalic virus and Toxoplasma gondii in a sample of the Monrovia population].", "content": "Cytomegalovirus and Toxoplasma gondii antibodies were titered in 133 serum specimens from students, physicians and technical staff of Monrovia hospital. The findings obtained show that both infections are widely spread: Cytomegalovirus antibody was detected in 81%, and Toxoplasma antibody in 70% of tested sera. No significative differences were observed among sera from different tribes and birth places.", "contents": "[Antibodies against the cytomegalic virus and Toxoplasma gondii in a sample of the Monrovia population]. Cytomegalovirus and Toxoplasma gondii antibodies were titered in 133 serum specimens from students, physicians and technical staff of Monrovia hospital. The findings obtained show that both infections are widely spread: Cytomegalovirus antibody was detected in 81%, and Toxoplasma antibody in 70% of tested sera. No significative differences were observed among sera from different tribes and birth places."}
{"id": "PMID:195865", "title": "Isolation and characterization of MMS-sensitive mutants of Saccharomyces cerevisiae.", "content": "We have isolated mutants sensitive to methyl methanesulfonate (MMS) in Saccharomyces cerevisiae. Alleles of rad1, rad4, rad52, rad55 and rad57 were found amoung these mms mutants. Twenty-nine of the mms mutants which complement the existing radiation-sensitive (rad and rev) mutants belong to 22 new complementation groups. Mutants from five complementation groups are sensitive only to MMS. Mutants of 11 complementation groups are sensitive to UV or X rays in addition to MMS, mutants of six complementation groups are sensitive to all three agents. The cross-sensitivities of these mms mutants to UV and X rays are discussed in terms of their possible involvement in DNA repair. Sporulation is reduced or absent in homozygous diploids of mms mutants from nine complementation groups.", "contents": "Isolation and characterization of MMS-sensitive mutants of Saccharomyces cerevisiae. We have isolated mutants sensitive to methyl methanesulfonate (MMS) in Saccharomyces cerevisiae. Alleles of rad1, rad4, rad52, rad55 and rad57 were found amoung these mms mutants. Twenty-nine of the mms mutants which complement the existing radiation-sensitive (rad and rev) mutants belong to 22 new complementation groups. Mutants from five complementation groups are sensitive only to MMS. Mutants of 11 complementation groups are sensitive to UV or X rays in addition to MMS, mutants of six complementation groups are sensitive to all three agents. The cross-sensitivities of these mms mutants to UV and X rays are discussed in terms of their possible involvement in DNA repair. Sporulation is reduced or absent in homozygous diploids of mms mutants from nine complementation groups."}
{"id": "PMID:195873", "title": "Enzymatic activity of Ammon's horn in the ontogenetic development of the rat.", "content": "Studies were performed on the activity of several enzymes in Ammon's horn of rat during an individual postembryonal development. For the studies rats of Wistar strain were used that were killed on the 1st, 3rd, 8th, 17th, 40th and 60th day after birth. In the experiment the brains were removed, cut, and the activity of dehydrogenases, phosphatases and esterases was revealed. During the performed studies some considerable differences were shown in the activity of several dehydrogenases, in each particular field of Ammon's horn, undergoing changes in the periods of ontogenetic development under study. Furthermore, some distinct differences in the phosphatases and esterases activity were revealed in each area of the Ammon's horn. Attention was drawn to a comparatively late histo-enzymatic maturation of Ammon's horn in comparison with other structures of the limbic system.", "contents": "Enzymatic activity of Ammon's horn in the ontogenetic development of the rat. Studies were performed on the activity of several enzymes in Ammon's horn of rat during an individual postembryonal development. For the studies rats of Wistar strain were used that were killed on the 1st, 3rd, 8th, 17th, 40th and 60th day after birth. In the experiment the brains were removed, cut, and the activity of dehydrogenases, phosphatases and esterases was revealed. During the performed studies some considerable differences were shown in the activity of several dehydrogenases, in each particular field of Ammon's horn, undergoing changes in the periods of ontogenetic development under study. Furthermore, some distinct differences in the phosphatases and esterases activity were revealed in each area of the Ammon's horn. Attention was drawn to a comparatively late histo-enzymatic maturation of Ammon's horn in comparison with other structures of the limbic system."}
{"id": "PMID:195874", "title": "Enzymatic activity of hydrolases in the spinal cord of rat after an acute and subacute calomel introxication.", "content": "Studies have been performed on changes in the activity of hydrolytic enzymes in spinal cord following a toxic action of calomel. With the use of a gastric cannule, the rats were being administered mercurous chloride. The first group were given Hg2Cl2 in a 0-05 g. dose for four days whereas the second experimental group received a 0-012 g. for ten days. As a result of the studies, both in an acute and subacute calomel intoxication, an increase in TTP-ase and NsE activity in spinal cord as well as a decrease in ATP-ase, AChE and AcP activity were found. It was also shown that mercurous chloride intoxication exerts of influence on AIP and BuTJ activity. In the discussion an attempt was made to explain some of the observed phenomena.", "contents": "Enzymatic activity of hydrolases in the spinal cord of rat after an acute and subacute calomel introxication. Studies have been performed on changes in the activity of hydrolytic enzymes in spinal cord following a toxic action of calomel. With the use of a gastric cannule, the rats were being administered mercurous chloride. The first group were given Hg2Cl2 in a 0-05 g. dose for four days whereas the second experimental group received a 0-012 g. for ten days. As a result of the studies, both in an acute and subacute calomel intoxication, an increase in TTP-ase and NsE activity in spinal cord as well as a decrease in ATP-ase, AChE and AcP activity were found. It was also shown that mercurous chloride intoxication exerts of influence on AIP and BuTJ activity. In the discussion an attempt was made to explain some of the observed phenomena."}
{"id": "PMID:195875", "title": "Phosphatases and esterases activity in the brain following an acute sublimate intoxication.", "content": "Experiment studies were performed on rats that were administered mercury chloride sublimate with a special gastric cannule in a single 6 mg dose for four consecutive days. As a result of the investigations some changes in the phosphates and esterases activity were revealed. The diminution of AcP, AIP, ATP-ase and AChE activity as well as in the increase in TPP-ase activity in the neurocytes, and also the appearance on NsE activity in many oligodendrocytes was observed. The fall in ATP-ase activity was, above all, observable in cerebral and cerebellar capillaries, which is, in the authors opinion, a manifestation of enzymatic damage to the blood-brain barrier due to a toxic action of mercuric chloride. In the discussion attention was drawn to differences in the degree of enzymatic activity between a mercuric chloride intoxication and that with mercurous chloride, as well as attempt was made to explain the pathogenetic mechanism of this phenomenon. Furthermore, notice was brought to the fact that in the course of sublimate encephalopathy no changes are observed in BuTJ activity.", "contents": "Phosphatases and esterases activity in the brain following an acute sublimate intoxication. Experiment studies were performed on rats that were administered mercury chloride sublimate with a special gastric cannule in a single 6 mg dose for four consecutive days. As a result of the investigations some changes in the phosphates and esterases activity were revealed. The diminution of AcP, AIP, ATP-ase and AChE activity as well as in the increase in TPP-ase activity in the neurocytes, and also the appearance on NsE activity in many oligodendrocytes was observed. The fall in ATP-ase activity was, above all, observable in cerebral and cerebellar capillaries, which is, in the authors opinion, a manifestation of enzymatic damage to the blood-brain barrier due to a toxic action of mercuric chloride. In the discussion attention was drawn to differences in the degree of enzymatic activity between a mercuric chloride intoxication and that with mercurous chloride, as well as attempt was made to explain the pathogenetic mechanism of this phenomenon. Furthermore, notice was brought to the fact that in the course of sublimate encephalopathy no changes are observed in BuTJ activity."}
{"id": "PMID:195876", "title": "The activity of Escherichia coli DNA-dependent RNA polymerase on DNA templates of different origin. The effect of cAMP.", "content": "DNA isolated from different T phages served as a better template for the synthetic activity of unmodified Escherichia coli RNA polymerase in the in vitro system than did the host DNA. cAMP significantly stimulated the activity of such a preparation of RNA polymerase. The stimulation was more pronounced with the host DNA template than with phage DNA. However, the synthetic activity of Escherichia coli RNA polymerase was greater in the presence of cAMP than without it when phage DNA served as the template.", "contents": "The activity of Escherichia coli DNA-dependent RNA polymerase on DNA templates of different origin. The effect of cAMP. DNA isolated from different T phages served as a better template for the synthetic activity of unmodified Escherichia coli RNA polymerase in the in vitro system than did the host DNA. cAMP significantly stimulated the activity of such a preparation of RNA polymerase. The stimulation was more pronounced with the host DNA template than with phage DNA. However, the synthetic activity of Escherichia coli RNA polymerase was greater in the presence of cAMP than without it when phage DNA served as the template."}
{"id": "PMID:195881", "title": "Serum hormone levels and tissue metabolism in pair-fed lean and obese Zucker rats.", "content": "Obese Zucker rats were either pair-fed to their lean litter-mates or fed ad lib, to determine the effect of hyperphagia on serum hormone levels and tissue metabolism as indicated by enzyme activities and in vitro metabolite flux. Hyperphagia was shown to be non-essential for the elevation in serum insulin and suppression in serum growth hormone and prolactin in the genetically obese rat. It was also shown that the increased liver cell lipogenic rate was not dependent on hyperphagia in the obese rat and that adipose cell lipogenesis was not significantly altered in the pair-fed obese rat. The utilization of alanine for glucose synthesis in vitro was similar for both lean and obese rats, but its utilization for fatty acid synthesis was higher in the obese rat. Data is presented which suggest that the inhibitory effect of glucagon on liver lipogenesis is blunted in the obese rat.", "contents": "Serum hormone levels and tissue metabolism in pair-fed lean and obese Zucker rats. Obese Zucker rats were either pair-fed to their lean litter-mates or fed ad lib, to determine the effect of hyperphagia on serum hormone levels and tissue metabolism as indicated by enzyme activities and in vitro metabolite flux. Hyperphagia was shown to be non-essential for the elevation in serum insulin and suppression in serum growth hormone and prolactin in the genetically obese rat. It was also shown that the increased liver cell lipogenic rate was not dependent on hyperphagia in the obese rat and that adipose cell lipogenesis was not significantly altered in the pair-fed obese rat. The utilization of alanine for glucose synthesis in vitro was similar for both lean and obese rats, but its utilization for fatty acid synthesis was higher in the obese rat. Data is presented which suggest that the inhibitory effect of glucagon on liver lipogenesis is blunted in the obese rat."}
{"id": "PMID:195885", "title": "Antidiuretic action of prolactin in the rat with diabetes insipidus.", "content": "Rats with hereditary hypothalamic diabetes insipidus, devoid of endogenous ADH, exhibited a prompt antidiuresis when injected subcutaneously or intraarterially with ovine prolactin. The antidiuresis was accompanied by a decrease in free water clearance and an increase in urine osmolality without a change in osmolal clearance or creatinine excretion. Measurement of PAH and insulin clearances indicated that prolactin had no effect on renal plasma flow or glomerular filtration rate. Prolactin injection caused a transient decrease in urinary sodium excretion, but proximal tubular sodium reabsorption, estimated by lissamine green transit time, was unaffected. The antidiuretic effect of prolactin could not be attributed to ADH contamination of the ovine prolactin preparation. Kidney cyclic AMP content was increased significantly 5 min after injection of prolactin. Thus, prolactin has an antidiuretic effect similar to that which occurs as a result of ADH action on the kidney and does not require either the release or the presence of ADH in order to cause the antidiuresis. Further, the impaired water excretion cannot be attributed to an increase in proximal tubular sodium reabsorption or to alteration of renal hemodynamics. It is suggested that prolactin has a direct ADH-like action on the kidney resulting in antidiuresis.", "contents": "Antidiuretic action of prolactin in the rat with diabetes insipidus. Rats with hereditary hypothalamic diabetes insipidus, devoid of endogenous ADH, exhibited a prompt antidiuresis when injected subcutaneously or intraarterially with ovine prolactin. The antidiuresis was accompanied by a decrease in free water clearance and an increase in urine osmolality without a change in osmolal clearance or creatinine excretion. Measurement of PAH and insulin clearances indicated that prolactin had no effect on renal plasma flow or glomerular filtration rate. Prolactin injection caused a transient decrease in urinary sodium excretion, but proximal tubular sodium reabsorption, estimated by lissamine green transit time, was unaffected. The antidiuretic effect of prolactin could not be attributed to ADH contamination of the ovine prolactin preparation. Kidney cyclic AMP content was increased significantly 5 min after injection of prolactin. Thus, prolactin has an antidiuretic effect similar to that which occurs as a result of ADH action on the kidney and does not require either the release or the presence of ADH in order to cause the antidiuresis. Further, the impaired water excretion cannot be attributed to an increase in proximal tubular sodium reabsorption or to alteration of renal hemodynamics. It is suggested that prolactin has a direct ADH-like action on the kidney resulting in antidiuresis."}
{"id": "PMID:195886", "title": "Effect of Mg2, ATP and some analogs on phosphorylase phosphatase from adrenal cortex.", "content": "The effect of Mg2, ATP and some of its analogs was studied on the spontaneously active and the ATP-Mg-dependent forms of phosphorylase phosphatase extracted from adrenal cortex. Inhibition of the spontaneously active form was observed with Mg2 (Ki - 9mM), ATP (Ki = 9micronM), 2'-doxy-ATP (Ki = 8 micronM), AtetraP (Ki = 9 micronM), AMP(CH2)PP (Ki = 11 micronM), ADP(CH2)P (Ki = 19 micronM), ADP(NH)P (Ki = 16micronM) and ADP (Ki = 25micronM). Activation of the ATP-Mg-dependent form was obtained with Mg2 (Ka = 0.55mM) (to a lower extent) and with ATP (Ka = 2micronM), 2'-deoxy-ATP (Ka = 6micronM) or AtetraP (Ka = 15micronM) in the presence of 0.5mM Mg2. Activation with AMP(CH2)PP was only observed in the presence of high concentrations (5mM) of Mg2 (Ka = 13micronM). No activation at all was observed with ADP(CH2)P or ADP(NH)P. Even though the activation of the ATP-Mg-dependent form does not seem to involve a kinase reaction, the stimulation by ATP or its analogs is rather specific, since it does not occur with analogs in which a methylene group or a nitrogen is substituted for the oxygen between the beta- and gamma-phosphates.", "contents": "Effect of Mg2, ATP and some analogs on phosphorylase phosphatase from adrenal cortex. The effect of Mg2, ATP and some of its analogs was studied on the spontaneously active and the ATP-Mg-dependent forms of phosphorylase phosphatase extracted from adrenal cortex. Inhibition of the spontaneously active form was observed with Mg2 (Ki - 9mM), ATP (Ki = 9micronM), 2'-doxy-ATP (Ki = 8 micronM), AtetraP (Ki = 9 micronM), AMP(CH2)PP (Ki = 11 micronM), ADP(CH2)P (Ki = 19 micronM), ADP(NH)P (Ki = 16micronM) and ADP (Ki = 25micronM). Activation of the ATP-Mg-dependent form was obtained with Mg2 (Ka = 0.55mM) (to a lower extent) and with ATP (Ka = 2micronM), 2'-deoxy-ATP (Ka = 6micronM) or AtetraP (Ka = 15micronM) in the presence of 0.5mM Mg2. Activation with AMP(CH2)PP was only observed in the presence of high concentrations (5mM) of Mg2 (Ka = 13micronM). No activation at all was observed with ADP(CH2)P or ADP(NH)P. Even though the activation of the ATP-Mg-dependent form does not seem to involve a kinase reaction, the stimulation by ATP or its analogs is rather specific, since it does not occur with analogs in which a methylene group or a nitrogen is substituted for the oxygen between the beta- and gamma-phosphates."}
{"id": "PMID:195887", "title": "Spectral evidence for a liver mitochondrial cytochrome P450 involved in bile acid metabolism.", "content": "Optical difference spectroscopy of liver mitochondria has revealed the presence of a cytochrome P450 species by its ligand reactions with carbon monoxide, metyrapone and diethylphenylphosphine. Its concentration of 0.15 nmol/mg mitochondrial protein is high enough to be detectable by ESR also. A microsomal contamination of the mitochondria could be excluded. Mitochondrial cytochrome P450 forms an enzyme-substrate complex with 5beta-cholestane-3alpha, 7alpha, 12alpha-triol with Ks value very similar to the Km value of the 26-hydroxylation of this substrate. This supports the existence in liver mitochondria of a cytochrome P450-dependent 26-monooxygenase for bile acid precursors, as previously postulated by us on the basis of a photochemical action spectrum.", "contents": "Spectral evidence for a liver mitochondrial cytochrome P450 involved in bile acid metabolism. Optical difference spectroscopy of liver mitochondria has revealed the presence of a cytochrome P450 species by its ligand reactions with carbon monoxide, metyrapone and diethylphenylphosphine. Its concentration of 0.15 nmol/mg mitochondrial protein is high enough to be detectable by ESR also. A microsomal contamination of the mitochondria could be excluded. Mitochondrial cytochrome P450 forms an enzyme-substrate complex with 5beta-cholestane-3alpha, 7alpha, 12alpha-triol with Ks value very similar to the Km value of the 26-hydroxylation of this substrate. This supports the existence in liver mitochondria of a cytochrome P450-dependent 26-monooxygenase for bile acid precursors, as previously postulated by us on the basis of a photochemical action spectrum."}
{"id": "PMID:195891", "title": "Referral follow-up by clinicians in a community mental health center.", "content": "In 1973 a study was conducted at the Western Psychiatric Institute in Pittsburgh to assess the extent of discrimination by clinicians against chronically ill clients in establishing initial treatment arrangements. Forty referrals (all simulated) were assigned to the center's five treatment teams; 20 of the referrals suggested a mild disorder, and 20 suggested a severe and chronic disorder. Premature termination of the study reduced the sample size from 40 to 29, and the findings regarding discrimination were inconclusive. However, the study revealed the unexpected finding that 34 per cent of the referrals received no follow-up. The author discusses the implications of that finding in relation to the basic principles of community mental health, and also to the large amounts of resources allocated to increasing service utilization in the center under study.", "contents": "Referral follow-up by clinicians in a community mental health center. In 1973 a study was conducted at the Western Psychiatric Institute in Pittsburgh to assess the extent of discrimination by clinicians against chronically ill clients in establishing initial treatment arrangements. Forty referrals (all simulated) were assigned to the center's five treatment teams; 20 of the referrals suggested a mild disorder, and 20 suggested a severe and chronic disorder. Premature termination of the study reduced the sample size from 40 to 29, and the findings regarding discrimination were inconclusive. However, the study revealed the unexpected finding that 34 per cent of the referrals received no follow-up. The author discusses the implications of that finding in relation to the basic principles of community mental health, and also to the large amounts of resources allocated to increasing service utilization in the center under study."}
{"id": "PMID:195892", "title": "Confirmation of the assignment of the Chimpanzee thymidine kinase and galactokinase genes to chromosome 19.", "content": "Chimpanzee-mouse hybrid cells were isolated by fusing chimpanzee HGPRT- cells and mouse TK- cells. Both biochemical and cytologic studies of these hybrid cells and BUDR resistant cells isolated from them showed that the TK and GaK genes are located on the chimpanzee chromosome 19.", "contents": "Confirmation of the assignment of the Chimpanzee thymidine kinase and galactokinase genes to chromosome 19. Chimpanzee-mouse hybrid cells were isolated by fusing chimpanzee HGPRT- cells and mouse TK- cells. Both biochemical and cytologic studies of these hybrid cells and BUDR resistant cells isolated from them showed that the TK and GaK genes are located on the chimpanzee chromosome 19."}
{"id": "PMID:195894", "title": "Induction of cell division in BALB/c-3T3 cells by phorbol myristate acetate or bovine serum: effects of inhibitors of cyclic AMP phosphodiesterase and Na+-K+-ATPase.", "content": "Cell division is induced in stationary cultures of BALB/c-3T3 mouse embryo cells without renewal of medium by addition of the tumor promoter, phorbol myristate acetate (PMA), or bovine serum. The addition of dbcAMP (10(-3) M) or other inhibitors of cAMP phosphodiesterase, papaverine (6.7 X 10(-6) M), Persantin (5 X 10(-5) M) or RO-20-1724 (10(-4) M), prevents cell replication induced by PMA or serum. In contrast, ouabain (10(-4) M) and N,N'-dicyclohexylcarbodiimide (10(-5) M), inhibitors of Na+-K+-ATPase activity, block the PMA-stimulated effect but do not inhibit serum-stimulated cell division. Several stages in the cell cycle are sensitive to dbcAMP addition. One is early in the G1 phase at the time of reinitiation of the cell cycle from a stationary (Go) phase, a second is associated with the G1-S transition, and a third with passage of cells from a post-S phase to mitosis. Based on observations of early morphological changes, responses of plasma membrane enzymes and effects of enzyme inhibitors, the stimulation of cell division in BALB/c-3T3 cells by PMA or serum appears to involve several membrane functions which may act in a cooperative manner.", "contents": "Induction of cell division in BALB/c-3T3 cells by phorbol myristate acetate or bovine serum: effects of inhibitors of cyclic AMP phosphodiesterase and Na+-K+-ATPase. Cell division is induced in stationary cultures of BALB/c-3T3 mouse embryo cells without renewal of medium by addition of the tumor promoter, phorbol myristate acetate (PMA), or bovine serum. The addition of dbcAMP (10(-3) M) or other inhibitors of cAMP phosphodiesterase, papaverine (6.7 X 10(-6) M), Persantin (5 X 10(-5) M) or RO-20-1724 (10(-4) M), prevents cell replication induced by PMA or serum. In contrast, ouabain (10(-4) M) and N,N'-dicyclohexylcarbodiimide (10(-5) M), inhibitors of Na+-K+-ATPase activity, block the PMA-stimulated effect but do not inhibit serum-stimulated cell division. Several stages in the cell cycle are sensitive to dbcAMP addition. One is early in the G1 phase at the time of reinitiation of the cell cycle from a stationary (Go) phase, a second is associated with the G1-S transition, and a third with passage of cells from a post-S phase to mitosis. Based on observations of early morphological changes, responses of plasma membrane enzymes and effects of enzyme inhibitors, the stimulation of cell division in BALB/c-3T3 cells by PMA or serum appears to involve several membrane functions which may act in a cooperative manner."}
{"id": "PMID:195895", "title": "Mycoplasma in African green monkey kidney cell cultures: biochemical detection and effects in virus-infected cells.", "content": "Among a number of techniques for the detection of mycoplasmal contamination in African green monkey kidney (AGMK) cell lines, the assay of uridine phosphorylase activity is unsuitable because of the presence of high levels of endogenous enzymatic activity. A thymidine phosphorylase test, however, based on the chromatographic analysis of radiolabeled thymidine breakdown, turned out to be a simple and sensitive mycoplasma detection method. We found, using the latter technique, that 0.22-micrometer-filtered virus inocula could still transfer mycoplasma unless treated with diethyl ether. The effect of mycoplasmal contamination on the synthesis of simian virus 40 and adenovirus in AGMK cells was negligible under the conditions used (no depletion of arginine). Incorporation of radioactive thymidine in viral macromolecules, however, was inhibited severely by the presence of mycoplasma.", "contents": "Mycoplasma in African green monkey kidney cell cultures: biochemical detection and effects in virus-infected cells. Among a number of techniques for the detection of mycoplasmal contamination in African green monkey kidney (AGMK) cell lines, the assay of uridine phosphorylase activity is unsuitable because of the presence of high levels of endogenous enzymatic activity. A thymidine phosphorylase test, however, based on the chromatographic analysis of radiolabeled thymidine breakdown, turned out to be a simple and sensitive mycoplasma detection method. We found, using the latter technique, that 0.22-micrometer-filtered virus inocula could still transfer mycoplasma unless treated with diethyl ether. The effect of mycoplasmal contamination on the synthesis of simian virus 40 and adenovirus in AGMK cells was negligible under the conditions used (no depletion of arginine). Incorporation of radioactive thymidine in viral macromolecules, however, was inhibited severely by the presence of mycoplasma."}
{"id": "PMID:195896", "title": "Effect of cyclic 3':5'-AMP derivatives prostaglandins and related agents on human chorionic gonadotropin secretion in human malignant trophoblast in culture.", "content": "The secretion of human chorionic gonadotropin (hCG) is stimulated by addition of N6, O2'-dibutyryl cyclic 3':5'-AMP (dbcAMP) or theophylline to normal term placenta and human malignant trophoblast cells in vitro. To understand better the specificity of this process, malignant trophoblast cultures were incubated with 3':5'-cyclic AMP (cAMP) derivatives, prostaglandins and other agents for 1 to 3 days, and the secretion of radioimmunoassayable hCG was measured. Whereas dbcAMP was the most potent agent in stimulating secretion of hCG, the N6--and O2'-monobutyryl derivatives of cAMP and phosphodiesterase inhibitors (theophylline, papaverine, 3-isobutyl-1-methylxanthine) also increased the secretion of the hormone. A slight increase in hCG secretion was observed following addition of adenine. By contrast, butyrate, cAMP, cyclic 3':5'-GMP (cGMP), dbcGMP, 5'-AMP, adenosine, L-epinephrine and prostaglandins E1, E2, F1a and F2a were ineffective. Particulate fractions from sonicates of malignant trophoblast cultures contained adenylate cyclase activity which was stimulated more than 10-fold by NaF, but not by either catecholamines or prostaglandins. The relatively specific stimulation of hCG secretion suggested that a regulatory process involving cAMP may have physiological significance in the trophoblast.", "contents": "Effect of cyclic 3':5'-AMP derivatives prostaglandins and related agents on human chorionic gonadotropin secretion in human malignant trophoblast in culture. The secretion of human chorionic gonadotropin (hCG) is stimulated by addition of N6, O2'-dibutyryl cyclic 3':5'-AMP (dbcAMP) or theophylline to normal term placenta and human malignant trophoblast cells in vitro. To understand better the specificity of this process, malignant trophoblast cultures were incubated with 3':5'-cyclic AMP (cAMP) derivatives, prostaglandins and other agents for 1 to 3 days, and the secretion of radioimmunoassayable hCG was measured. Whereas dbcAMP was the most potent agent in stimulating secretion of hCG, the N6--and O2'-monobutyryl derivatives of cAMP and phosphodiesterase inhibitors (theophylline, papaverine, 3-isobutyl-1-methylxanthine) also increased the secretion of the hormone. A slight increase in hCG secretion was observed following addition of adenine. By contrast, butyrate, cAMP, cyclic 3':5'-GMP (cGMP), dbcGMP, 5'-AMP, adenosine, L-epinephrine and prostaglandins E1, E2, F1a and F2a were ineffective. Particulate fractions from sonicates of malignant trophoblast cultures contained adenylate cyclase activity which was stimulated more than 10-fold by NaF, but not by either catecholamines or prostaglandins. The relatively specific stimulation of hCG secretion suggested that a regulatory process involving cAMP may have physiological significance in the trophoblast."}
{"id": "PMID:195900", "title": "Detection of mitogen-activated T and non-T lymphocytes by virus plaque assay. Virus plaque assay on the cells fractionated by unit gravity sedimentation.", "content": "Virus plaque assay (VPA) was utilized for the quantitative evaluation of activated lymphocytes. We examined what types of cells, especially which of activated T and non-T lymphocytes, were detected as infective centres after infection with vesicular stomatitis virus. Marked increases in DNA synthesis and in virus-plaque forming cells (V-PFC) were observed not only during the activation of T lymphocytes with Con A, but also, though to a lesser extent, during the activation with lipopolysaccharide (LPS) of non-T lymphocyte preparations of nude spleen from which theta-positive lymphocytes and macrophages were completely depleted. The latter observation was further confirmed by the VPA on the populations enriched in LPS-activated non-T lymphocytes fractionated by the unit gravity sedimentation method. Fast sedimenting cells were found to be more active in DNA synthesis and contained more infective centres after infection than those sedimenting slowly and original unfractionated cells. Both the capacity for DNA synthesis and virus-replication were considered to be general properties accompanying lymphocyte activation.", "contents": "Detection of mitogen-activated T and non-T lymphocytes by virus plaque assay. Virus plaque assay on the cells fractionated by unit gravity sedimentation. Virus plaque assay (VPA) was utilized for the quantitative evaluation of activated lymphocytes. We examined what types of cells, especially which of activated T and non-T lymphocytes, were detected as infective centres after infection with vesicular stomatitis virus. Marked increases in DNA synthesis and in virus-plaque forming cells (V-PFC) were observed not only during the activation of T lymphocytes with Con A, but also, though to a lesser extent, during the activation with lipopolysaccharide (LPS) of non-T lymphocyte preparations of nude spleen from which theta-positive lymphocytes and macrophages were completely depleted. The latter observation was further confirmed by the VPA on the populations enriched in LPS-activated non-T lymphocytes fractionated by the unit gravity sedimentation method. Fast sedimenting cells were found to be more active in DNA synthesis and contained more infective centres after infection than those sedimenting slowly and original unfractionated cells. Both the capacity for DNA synthesis and virus-replication were considered to be general properties accompanying lymphocyte activation."}
{"id": "PMID:195901", "title": "Functional studies on human peritoneal eosinophils.", "content": "A number of functional studies were performed on essentially pure eosinophil preparations obtained from the ascitic fluid of a patient with eosinophilic gastroenteritis. These cells responded to chemotactic factors including a bacterial factor, partially purified C5a, and factors generated from serum or ascitic fluid. The chemotactic activity generated in the patient's ascitic fluid was capable of attracting both neutrophils and eosinophils, was dependent on the presence of complement components, and was identified as C5a. Metabolic studies demonstrated that particle ingestion by eosinophils was associated with a marked increase in hexose monophosphate shunt activity ([1-14C]glucose oxidation), H2O2 formation ([14C]formate oxidation), superoxide anion generation, chemiluminescence, thyroid hormone degradation, iodination, and estrogen binding. This postphagocytic metabolic burst by eosinophils was qualitatively similar to that observed in neutrophils, but for several parameters the eosinophil response was greater than the neutrophil response.", "contents": "Functional studies on human peritoneal eosinophils. A number of functional studies were performed on essentially pure eosinophil preparations obtained from the ascitic fluid of a patient with eosinophilic gastroenteritis. These cells responded to chemotactic factors including a bacterial factor, partially purified C5a, and factors generated from serum or ascitic fluid. The chemotactic activity generated in the patient's ascitic fluid was capable of attracting both neutrophils and eosinophils, was dependent on the presence of complement components, and was identified as C5a. Metabolic studies demonstrated that particle ingestion by eosinophils was associated with a marked increase in hexose monophosphate shunt activity ([1-14C]glucose oxidation), H2O2 formation ([14C]formate oxidation), superoxide anion generation, chemiluminescence, thyroid hormone degradation, iodination, and estrogen binding. This postphagocytic metabolic burst by eosinophils was qualitatively similar to that observed in neutrophils, but for several parameters the eosinophil response was greater than the neutrophil response."}
{"id": "PMID:195902", "title": "Development of cell-mediated immunity to Epstein-Barr herpesvirus in infectious mononucleosis as shown by leukocyte migration inhibition.", "content": "Eight patients with infectious mononucleosis, aged between 8 and 24, were studied for cell-mediated immunity by the in vitro leukocyte migration inhibition test at acute and convalescent stages. Follow-up studies were also carried out at up to 4 months after clinical illness. Cell-mediated immunity to Epstein-Barr virus (EBV) in the peripheral leukocytes from these patients was absent or incipient in all cases during the acute phase, although it was present in lymphocytes from a biopsied lymph node obtained from one of the patients. In contrast, cell-mediated immunity to EBV was detected readily in peripheral leukocytes obtained during convalescence and in the follow-up studies. A blocking factor that abrogated leukocyte migration inhibition induced by EBV antigen was detected in acute and convalescent sera obtained from six of eight patients, whereas serum antinuclear autoantibodies were detected in the two patients whose sera failed to block leukocyte migration inhibition. When sera were fractionated, this blocking effect was observed only in the serum immunoglobulin G fractions. In follow-up studies, neither the blocking factor nor the antinuclear autoantibodies were found in the sera collected.", "contents": "Development of cell-mediated immunity to Epstein-Barr herpesvirus in infectious mononucleosis as shown by leukocyte migration inhibition. Eight patients with infectious mononucleosis, aged between 8 and 24, were studied for cell-mediated immunity by the in vitro leukocyte migration inhibition test at acute and convalescent stages. Follow-up studies were also carried out at up to 4 months after clinical illness. Cell-mediated immunity to Epstein-Barr virus (EBV) in the peripheral leukocytes from these patients was absent or incipient in all cases during the acute phase, although it was present in lymphocytes from a biopsied lymph node obtained from one of the patients. In contrast, cell-mediated immunity to EBV was detected readily in peripheral leukocytes obtained during convalescence and in the follow-up studies. A blocking factor that abrogated leukocyte migration inhibition induced by EBV antigen was detected in acute and convalescent sera obtained from six of eight patients, whereas serum antinuclear autoantibodies were detected in the two patients whose sera failed to block leukocyte migration inhibition. When sera were fractionated, this blocking effect was observed only in the serum immunoglobulin G fractions. In follow-up studies, neither the blocking factor nor the antinuclear autoantibodies were found in the sera collected."}
{"id": "PMID:195903", "title": "Chemiluminescence spectra of human myeloperoxidase and polymorphonuclear leukocytes.", "content": "The light emission spectra of myeloperoxidase-H2O2-Cl- and phagocytizing polymorphonuclear leukocytes were estimated by a computer simulation technique by using light transmittance data from nine band-pass filters. No shift in the chemiluminescence spectrum of either system was observed during the course of the reactions, suggesting that the light-generating mechanisms remain constant after their initiation. Transmittances were virtually identical for both myeloperoxidase-H2-O2-Cl- and polymorphonuclear leukocyte reactions, suggesting that the light-generating mechanisms are identical and leading to the estimation of nearly identical spectra. Both spectra were broad, with maximum light emission near 570 nm.", "contents": "Chemiluminescence spectra of human myeloperoxidase and polymorphonuclear leukocytes. The light emission spectra of myeloperoxidase-H2O2-Cl- and phagocytizing polymorphonuclear leukocytes were estimated by a computer simulation technique by using light transmittance data from nine band-pass filters. No shift in the chemiluminescence spectrum of either system was observed during the course of the reactions, suggesting that the light-generating mechanisms remain constant after their initiation. Transmittances were virtually identical for both myeloperoxidase-H2-O2-Cl- and polymorphonuclear leukocyte reactions, suggesting that the light-generating mechanisms are identical and leading to the estimation of nearly identical spectra. Both spectra were broad, with maximum light emission near 570 nm."}
{"id": "PMID:195905", "title": "On the protection of E. coli against radiation lethality by ascorbate combined with tetracycline.", "content": "The radioprotective action in E. coli ATCC 9637 of ascorbate added to media containing the weak sensitizer, tetracycline (effect described by Pittillo and Lucas (1967)), was found to be dependent on the presence of metal catalysts of the autoxidation of ascorbate. Thus, the protective action of ascorbate + tetracycline as well as the rate of autoxidation of ascorbate in this mixture were enhanced by 0.1 micron Cu, and these effects were counteracted by pyrophosphate probably through chelation of iron that contaminates phosphate. A suppression of metabolism is apparently involved in the combined action as judged by the decrease of incorporation of labelled uridine.", "contents": "On the protection of E. coli against radiation lethality by ascorbate combined with tetracycline. The radioprotective action in E. coli ATCC 9637 of ascorbate added to media containing the weak sensitizer, tetracycline (effect described by Pittillo and Lucas (1967)), was found to be dependent on the presence of metal catalysts of the autoxidation of ascorbate. Thus, the protective action of ascorbate + tetracycline as well as the rate of autoxidation of ascorbate in this mixture were enhanced by 0.1 micron Cu, and these effects were counteracted by pyrophosphate probably through chelation of iron that contaminates phosphate. A suppression of metabolism is apparently involved in the combined action as judged by the decrease of incorporation of labelled uridine."}
{"id": "PMID:195906", "title": "[Vitamin A-vitamin D3 relationship in growing rats].", "content": "A relation vitamin A - vitamin D3 exists in diet for growing rats. When this decreases from 5 (microgram A - IU D3) or 15 (IU A - IU D3) to 1,25 (microgram/IU) or 3,75 (IU/IU) growth, calcemia are increasing but vitamin A hepatic storage is decreasing. In other words for a same quantity of retinol, cholecalciferol's level in diet determines hepatic stores of vitamin A. General aspect of this question is discussed.", "contents": "[Vitamin A-vitamin D3 relationship in growing rats]. A relation vitamin A - vitamin D3 exists in diet for growing rats. When this decreases from 5 (microgram A - IU D3) or 15 (IU A - IU D3) to 1,25 (microgram/IU) or 3,75 (IU/IU) growth, calcemia are increasing but vitamin A hepatic storage is decreasing. In other words for a same quantity of retinol, cholecalciferol's level in diet determines hepatic stores of vitamin A. General aspect of this question is discussed."}
{"id": "PMID:195907", "title": "Subcellular distribution of thiamine-pyrophosphokinase and thiamine-pyrophosphatase activities in rat isolated enterocytes.", "content": "Starting from mucosal cells, isolated from rat small intestine, subcellular fractionation was carried out. Four fractions were prepared and characterized by marker enzymes and electron microscopic examination: nuclei plus microvilli, mitochondria, microsomes and supernatant. Thiamine-pyrophosphokinase activity was localized mainly in the supernatant fraction, with minor amount in mitchondria and microsomes. On the contrary thiamine-pyrophosphatase activity was present only in the particulate fractions (especially in microsomes), being completely absent from the supernatant.", "contents": "Subcellular distribution of thiamine-pyrophosphokinase and thiamine-pyrophosphatase activities in rat isolated enterocytes. Starting from mucosal cells, isolated from rat small intestine, subcellular fractionation was carried out. Four fractions were prepared and characterized by marker enzymes and electron microscopic examination: nuclei plus microvilli, mitochondria, microsomes and supernatant. Thiamine-pyrophosphokinase activity was localized mainly in the supernatant fraction, with minor amount in mitchondria and microsomes. On the contrary thiamine-pyrophosphatase activity was present only in the particulate fractions (especially in microsomes), being completely absent from the supernatant."}
{"id": "PMID:195909", "title": "A superoxide-producing system in the conjunctival mucus thread.", "content": "In normal sterile eyes, the conjunctival mucus thread is capable of reducing the vital stain iodonitrotetrazolium (INT). The greatly increased amount of INT reduction in bacterial conjunctivitis has been used as a clinical test for this disorder. We find that native superoxide dismutase, but not the heat inactivated enzyme, inhibits INT reduction by the conjunctival mucus thread in vitro as well as in vivo in sterile rabbit eyes. Furthermore, 3,4-dihydroxybenzoic acid (DHBA), a scavenger of superoxide radical (O2-), inhibits INT reduction by the mucus thread. We conclude that INT reduction by the mucus thread is due to a superoxide radical-producing system similar to that apparently responsible for the tetrazolium-reducing properties of granulocytes and other phagocytes. This oxygen radical-producing system may serve as a defense against infection and possibly as a mediator of the conjunctival inflammatory response.", "contents": "A superoxide-producing system in the conjunctival mucus thread. In normal sterile eyes, the conjunctival mucus thread is capable of reducing the vital stain iodonitrotetrazolium (INT). The greatly increased amount of INT reduction in bacterial conjunctivitis has been used as a clinical test for this disorder. We find that native superoxide dismutase, but not the heat inactivated enzyme, inhibits INT reduction by the conjunctival mucus thread in vitro as well as in vivo in sterile rabbit eyes. Furthermore, 3,4-dihydroxybenzoic acid (DHBA), a scavenger of superoxide radical (O2-), inhibits INT reduction by the mucus thread. We conclude that INT reduction by the mucus thread is due to a superoxide radical-producing system similar to that apparently responsible for the tetrazolium-reducing properties of granulocytes and other phagocytes. This oxygen radical-producing system may serve as a defense against infection and possibly as a mediator of the conjunctival inflammatory response."}
{"id": "PMID:195911", "title": "Rapid detection of human cytomegalovirus and herpesvirus hominis IgM antibody by the immunoperoxidase technique.", "content": "Immunoglobulin M (IgM) to human cytomegalovirus (CMV) and herpesvirus hominis (HVH, types 1 and 2) has been searched for in a group of patients with congenital and recent CMV and HVH infections and also in a group of patients with remote CMV and recurrent HVH infections, using the immunoperoxidase antibody technique (IPA) as compared to a technique using sucrose density gradient differential centrifugation. Both techniques detected the same positive samples. High IgM antibody titers (1:32-1:512) were observed in all cases of primary CMV and HVH infection, whereas low titers (1:8-1:16) were found in congenital infections. The IPA technique is sensitive, specific and useful for rapid diagnosis of recent and congenital CMV and HVH infections.", "contents": "Rapid detection of human cytomegalovirus and herpesvirus hominis IgM antibody by the immunoperoxidase technique. Immunoglobulin M (IgM) to human cytomegalovirus (CMV) and herpesvirus hominis (HVH, types 1 and 2) has been searched for in a group of patients with congenital and recent CMV and HVH infections and also in a group of patients with remote CMV and recurrent HVH infections, using the immunoperoxidase antibody technique (IPA) as compared to a technique using sucrose density gradient differential centrifugation. Both techniques detected the same positive samples. High IgM antibody titers (1:32-1:512) were observed in all cases of primary CMV and HVH infection, whereas low titers (1:8-1:16) were found in congenital infections. The IPA technique is sensitive, specific and useful for rapid diagnosis of recent and congenital CMV and HVH infections."}
{"id": "PMID:195912", "title": "A novel approach to study the DNA of herpes zoster virus.", "content": "Herpes zoster virus DNA was isolated from infected human embryo lung cells because it is released into the \"Hirt supernatant\". The buoyant density of the virus DNA was found to be slightly higher than that of cellular DNA. The molecular weight of this DNA was estimated to be 92 x 10(6) daltons by cosedimentation with T4 DNA in neutral sucrose gradients. As with the DNA of other herpesviruses, the DNA of herpes zoster virus is fragmented when denatured under alkaline conditions and is therefore \"alkali-labile\". Studies of virus DNA using reassociation kinetics reveal that the kinetic complexity of the DNA correlates with the genome size as estimated by sucrose gradient sedimentation.", "contents": "A novel approach to study the DNA of herpes zoster virus. Herpes zoster virus DNA was isolated from infected human embryo lung cells because it is released into the \"Hirt supernatant\". The buoyant density of the virus DNA was found to be slightly higher than that of cellular DNA. The molecular weight of this DNA was estimated to be 92 x 10(6) daltons by cosedimentation with T4 DNA in neutral sucrose gradients. As with the DNA of other herpesviruses, the DNA of herpes zoster virus is fragmented when denatured under alkaline conditions and is therefore \"alkali-labile\". Studies of virus DNA using reassociation kinetics reveal that the kinetic complexity of the DNA correlates with the genome size as estimated by sucrose gradient sedimentation."}
{"id": "PMID:195913", "title": "The antibody response following hepatitis A infection.", "content": "A specific IgM response to hepatitis A virus was detected in sera from patients suffering acute hepatitis A infection. The presence of virus-specific IgM in 19S components of acute and early convalescent phase sera was detected by immune electron microscopy and solid-phase radioimmunoassay. The presence of virus-specific IgM in whole serum specimens was demonstrated by indirect immunoferritin labeling. Following acute infection, however, the major immunoglobulin response appears to be IgG, since titers of specific 7S and whole serum antibody were very similar.", "contents": "The antibody response following hepatitis A infection. A specific IgM response to hepatitis A virus was detected in sera from patients suffering acute hepatitis A infection. The presence of virus-specific IgM in 19S components of acute and early convalescent phase sera was detected by immune electron microscopy and solid-phase radioimmunoassay. The presence of virus-specific IgM in whole serum specimens was demonstrated by indirect immunoferritin labeling. Following acute infection, however, the major immunoglobulin response appears to be IgG, since titers of specific 7S and whole serum antibody were very similar."}
{"id": "PMID:195910", "title": "Evaluation of perfluoroctylbromide for lymphography in the dog: comparison with ethiodol.", "content": "The efficacy and safety of perfluoroctylbromide as a diagnostic contrast agent for direct lymphography was studied in mongrel dogs. This radiopaque perfluorocarbon has several advantages over Ethiodol. The liquid compound has injection times  one-fifth of that required for Ethiodol. When dosages were three to four times that necessary for radiograms, the lungs of perfluoroctylbromide dogs tolerated the increase better than the Ethiodol dogs. Although the radiopacity is less, radiographs were acceptable. The less radiopacity of the fluoroctylbromide nodes may be of greater significance in the larger body of the human.", "contents": "Evaluation of perfluoroctylbromide for lymphography in the dog: comparison with ethiodol. The efficacy and safety of perfluoroctylbromide as a diagnostic contrast agent for direct lymphography was studied in mongrel dogs. This radiopaque perfluorocarbon has several advantages over Ethiodol. The liquid compound has injection times  one-fifth of that required for Ethiodol. When dosages were three to four times that necessary for radiograms, the lungs of perfluoroctylbromide dogs tolerated the increase better than the Ethiodol dogs. Although the radiopacity is less, radiographs were acceptable. The less radiopacity of the fluoroctylbromide nodes may be of greater significance in the larger body of the human."}
{"id": "PMID:195914", "title": "Propagation of a B-tropic murine leukemia virus in N-type cells in the presence of different murine sarcoma viruses.", "content": "B-tropic MuLV, WN1802B, was converted to NB-tropic after 5 days of propagation in its nonpermissive N-type MLg or C3H2K cells in the presence of the S + L - MuSV, but not in the presence of the Harvey or Kirsten strains of MsSV.", "contents": "Propagation of a B-tropic murine leukemia virus in N-type cells in the presence of different murine sarcoma viruses. B-tropic MuLV, WN1802B, was converted to NB-tropic after 5 days of propagation in its nonpermissive N-type MLg or C3H2K cells in the presence of the S + L - MuSV, but not in the presence of the Harvey or Kirsten strains of MsSV."}
{"id": "PMID:195915", "title": "Ultrastructure of hepatocellular carcinoma in a cirrhotic liver.", "content": "Hepatoma cells, though sharing many similarities with non-neoplastic hepatocytes, showed conspicuous alterations--increased nuclear/cytoplasmic ratio, intranuclear invapinations of cytoplasm, lipoid material, high mitotic activity, and the presence of abundant small fat droplets and glycogen in the cytoplasm. \"Capillarization\" of sinusoids was a constant feature with the appearance of junctions between endothelial cells, deposition of fibrillary material in Disse's spaces, flattening of hepatocyte microvilli and deposition of basement-membrane-like material. Abundant microtubules and the presence of annulate lamellae were other features noted in the tumor cells.", "contents": "Ultrastructure of hepatocellular carcinoma in a cirrhotic liver. Hepatoma cells, though sharing many similarities with non-neoplastic hepatocytes, showed conspicuous alterations--increased nuclear/cytoplasmic ratio, intranuclear invapinations of cytoplasm, lipoid material, high mitotic activity, and the presence of abundant small fat droplets and glycogen in the cytoplasm. \"Capillarization\" of sinusoids was a constant feature with the appearance of junctions between endothelial cells, deposition of fibrillary material in Disse's spaces, flattening of hepatocyte microvilli and deposition of basement-membrane-like material. Abundant microtubules and the presence of annulate lamellae were other features noted in the tumor cells."}
{"id": "PMID:195916", "title": "[Myoblastoma of the larynx (author's transl)].", "content": "The case of a 35-year-old man in whom a broad-based tumour of the left vocal cord was found to be the cause of hoarseness of 4 months' duration is reported. The tumour was completely removed and proved to be a myoblastoma. Twelve months postoperatively there was no recurrence. Whether these are true neoplasms in all cases is still uncertain. Recurrence, multifocal origin and malignant change, factors which cannot be excluded, underline the need for the long-term follow-up.", "contents": "[Myoblastoma of the larynx (author's transl)]. The case of a 35-year-old man in whom a broad-based tumour of the left vocal cord was found to be the cause of hoarseness of 4 months' duration is reported. The tumour was completely removed and proved to be a myoblastoma. Twelve months postoperatively there was no recurrence. Whether these are true neoplasms in all cases is still uncertain. Recurrence, multifocal origin and malignant change, factors which cannot be excluded, underline the need for the long-term follow-up."}
{"id": "PMID:195917", "title": "[Observations during tonsillectomy in angiomatous phakomatoses of the head (author's transl)].", "content": "The problems encountered during tonsillectomy in a patient with a vascular malformation (flame nevus), mandibular hypertrophy, and extensive arteriovenous malformations involving the external carotid arteries are described. The inclusion of the patient in the Sturge-Weber or Klippel-Trenaunay Syndromes is discussed.", "contents": "[Observations during tonsillectomy in angiomatous phakomatoses of the head (author's transl)]. The problems encountered during tonsillectomy in a patient with a vascular malformation (flame nevus), mandibular hypertrophy, and extensive arteriovenous malformations involving the external carotid arteries are described. The inclusion of the patient in the Sturge-Weber or Klippel-Trenaunay Syndromes is discussed."}
{"id": "PMID:195918", "title": "[Computer tomography in otorhinolaryngology--a preliminary report (author's transl)].", "content": "The diagnostic possibilities of computer tomography in otorhinolaryngology are presented with the aid of typical and unusual cases. Good topographical demonstration of pathologies and the assessment of tissue densities with this method are emphasized.", "contents": "[Computer tomography in otorhinolaryngology--a preliminary report (author's transl)]. The diagnostic possibilities of computer tomography in otorhinolaryngology are presented with the aid of typical and unusual cases. Good topographical demonstration of pathologies and the assessment of tissue densities with this method are emphasized."}
{"id": "PMID:195925", "title": "Effect of physical training on control mechanisms of lipolysis in rat fat cell ghosts.", "content": "Fat cell ghosts and homogenates of fat cells were used to study the influence of training on the regulatory system for lipolysis in adipose tissue of female rats. A training effect was identified from elevated succinate dehydrogenase activities in the soleus and plantaris muscles. Neither basal nor maximal (NaF-stimulated) adenylate cyclase activities per mg protein of fat cell ghosts were altered by training. Fluoride-stimulated adenylate cyclase activity per microgram DNA was lower in the trained than untrained group. Adenylate cyclase activities in response to norepinephrine expressed either on a per mg protein or per microgram DNA basis were lower (P less than 0.05) in fat cell ghosts from trained rats. Phosphodiesterase activity was higher (P less than 0.05) in fat cell ghosts from trained rats for cyclic AMP concentrations of 1--5.0 micrometer. The apparent Km's of phosphodiesterase were 1.19 and 2.0 micrometer of cyclic AMP for the untrained and trained groups, respectively (P less than 0.05). Protein kinase activity in the supernatant fraction of homogenates of fat cells was unchanged due to training. The overall effect of training was to blunt the system for cyclic AMP production in rat adipocytes. This may explain, at least partially, the lower plasma free fatty acid levels observed in trained compared to untrained persons during submaximal exercise.", "contents": "Effect of physical training on control mechanisms of lipolysis in rat fat cell ghosts. Fat cell ghosts and homogenates of fat cells were used to study the influence of training on the regulatory system for lipolysis in adipose tissue of female rats. A training effect was identified from elevated succinate dehydrogenase activities in the soleus and plantaris muscles. Neither basal nor maximal (NaF-stimulated) adenylate cyclase activities per mg protein of fat cell ghosts were altered by training. Fluoride-stimulated adenylate cyclase activity per microgram DNA was lower in the trained than untrained group. Adenylate cyclase activities in response to norepinephrine expressed either on a per mg protein or per microgram DNA basis were lower (P less than 0.05) in fat cell ghosts from trained rats. Phosphodiesterase activity was higher (P less than 0.05) in fat cell ghosts from trained rats for cyclic AMP concentrations of 1--5.0 micrometer. The apparent Km's of phosphodiesterase were 1.19 and 2.0 micrometer of cyclic AMP for the untrained and trained groups, respectively (P less than 0.05). Protein kinase activity in the supernatant fraction of homogenates of fat cells was unchanged due to training. The overall effect of training was to blunt the system for cyclic AMP production in rat adipocytes. This may explain, at least partially, the lower plasma free fatty acid levels observed in trained compared to untrained persons during submaximal exercise."}
{"id": "PMID:195926", "title": "Limits on VA/Q distributions from analysis of experimental inert gas elimination.", "content": "Distributions of ventilation-perfusion ratios (VA/Q) actually present in the lung cannot be exactly recovered using current inert gas elimination methods, principally because of the limited number of gases and errors in their measurement. The amount of information that can be gained is studied here. When six gases are used the results are difficult to visualize so that a graphical analysis is first given for only two gases. Methods are proposed for 1) the probabilistic description of retentions compatible with a set of measured values of all six gases, and 2) the placing of limits on the associated VA/Q distributions. It is found that the variability among distributions with compatible retentions depends greatly on the particular set of data. Distributions consisting of a single or of two separated narrow modes can be identified reliably.", "contents": "Limits on VA/Q distributions from analysis of experimental inert gas elimination. Distributions of ventilation-perfusion ratios (VA/Q) actually present in the lung cannot be exactly recovered using current inert gas elimination methods, principally because of the limited number of gases and errors in their measurement. The amount of information that can be gained is studied here. When six gases are used the results are difficult to visualize so that a graphical analysis is first given for only two gases. Methods are proposed for 1) the probabilistic description of retentions compatible with a set of measured values of all six gases, and 2) the placing of limits on the associated VA/Q distributions. It is found that the variability among distributions with compatible retentions depends greatly on the particular set of data. Distributions consisting of a single or of two separated narrow modes can be identified reliably."}
{"id": "PMID:195928", "title": "Partial purification of ferredoxin from Ruminococcus albus and its role in pyruvate metabolism and reduction of nicotinamide adenine dinucleotide by H2.", "content": "Extracts of Ruminococcus albus were not able to convert pyruvate to acetyl phosphate, CO2, and H2 after passage through a diethylaminoethyl (DEAE)-cellulose column. Activity was restored by a brown protein fraction eluted from the column with 0.4 M Cl-. The protein was partially purified and shown to have the spectral and biological characteristics of ferredoxin. R. albus ferredoxin, Clostridium pasteurianum ferredoxin, and methyl viologen restored activity for pyruvate decomposition by DEAE-cellulose-treated R. albus extracts. R. albus or C. pasteurianum ferredoxin restored the ability of DEAE-cellulose-treated C. pasteurianum extracts to form H2 and acetyl phosphate from pyruvate. Ferredoxin-free extracts of R. albus reduced nicotinamide adenine dinucleotide (NAD) when supplemented with R. albus or C. pasteurianum ferredoxin or with methyl viologen. These extracts reduced NADP with H2 poorly unless both ferredoxin and NAD were added, which indicates the presence of an NADH:NADP transhydrogenase. Flavin mononucleotide and flavin adenine dinucleotide were rapidly reduced by H2 by ferredoxin-free extracts in the absence of ferredoxin.", "contents": "Partial purification of ferredoxin from Ruminococcus albus and its role in pyruvate metabolism and reduction of nicotinamide adenine dinucleotide by H2. Extracts of Ruminococcus albus were not able to convert pyruvate to acetyl phosphate, CO2, and H2 after passage through a diethylaminoethyl (DEAE)-cellulose column. Activity was restored by a brown protein fraction eluted from the column with 0.4 M Cl-. The protein was partially purified and shown to have the spectral and biological characteristics of ferredoxin. R. albus ferredoxin, Clostridium pasteurianum ferredoxin, and methyl viologen restored activity for pyruvate decomposition by DEAE-cellulose-treated R. albus extracts. R. albus or C. pasteurianum ferredoxin restored the ability of DEAE-cellulose-treated C. pasteurianum extracts to form H2 and acetyl phosphate from pyruvate. Ferredoxin-free extracts of R. albus reduced nicotinamide adenine dinucleotide (NAD) when supplemented with R. albus or C. pasteurianum ferredoxin or with methyl viologen. These extracts reduced NADP with H2 poorly unless both ferredoxin and NAD were added, which indicates the presence of an NADH:NADP transhydrogenase. Flavin mononucleotide and flavin adenine dinucleotide were rapidly reduced by H2 by ferredoxin-free extracts in the absence of ferredoxin."}
{"id": "PMID:195929", "title": "Mutants of luminous bacteria with an altered control of luciferase synthesis.", "content": "Arginine is known to increase the luminescence in vivo and in vitro of the marine bacterium Beneckea harveyi growing in minimal medium. Mutants in which this arginine effect is either diminished, or absent were isolated as bright clones on a minimal medium after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. On a minimal medium both with and without added arginine and also on complex medium, these \"minimal bright\" mutants produce higher levels of luminescence than the wild type both in vivo and in vitro. This is attributed to the production of an increased amount of luciferase, which itself is wild type in terms of its specific activity.", "contents": "Mutants of luminous bacteria with an altered control of luciferase synthesis. Arginine is known to increase the luminescence in vivo and in vitro of the marine bacterium Beneckea harveyi growing in minimal medium. Mutants in which this arginine effect is either diminished, or absent were isolated as bright clones on a minimal medium after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. On a minimal medium both with and without added arginine and also on complex medium, these \"minimal bright\" mutants produce higher levels of luminescence than the wild type both in vivo and in vitro. This is attributed to the production of an increased amount of luciferase, which itself is wild type in terms of its specific activity."}
{"id": "PMID:195930", "title": "Regulation of the arginine dihydrolase pathway in Clostridium sporogenes.", "content": "Arginine deiminase activity was induced during the vegetative growth of Clostridium sporogenes. The enzyme was sensitive to catabolite repression. The other enzymes of the arginine dihydrolase pathway, namely, ornithine carbamoyl-transferase and carbamate kinase, did not show such variation.", "contents": "Regulation of the arginine dihydrolase pathway in Clostridium sporogenes. Arginine deiminase activity was induced during the vegetative growth of Clostridium sporogenes. The enzyme was sensitive to catabolite repression. The other enzymes of the arginine dihydrolase pathway, namely, ornithine carbamoyl-transferase and carbamate kinase, did not show such variation."}
{"id": "PMID:195931", "title": "Role of cyclic adenosine 3',5'-monophosphate on cessation of respiration in ultraviolet-irradiated Escherichia coli.", "content": "The addition of cyclic adenosine 3',5'-monophosphate (cAMP) to ultraviolet-irradiated Escherichia coli B/r cultures causes additional cells to cease respiring and to die. These effects of cAMP are greater on glucose-grown cells, where the effects of ultraviolet radiations alone are smaller and where the intracellular concentrations of cAMP are known to be lower.", "contents": "Role of cyclic adenosine 3',5'-monophosphate on cessation of respiration in ultraviolet-irradiated Escherichia coli. The addition of cyclic adenosine 3',5'-monophosphate (cAMP) to ultraviolet-irradiated Escherichia coli B/r cultures causes additional cells to cease respiring and to die. These effects of cAMP are greater on glucose-grown cells, where the effects of ultraviolet radiations alone are smaller and where the intracellular concentrations of cAMP are known to be lower."}
{"id": "PMID:195932", "title": "Release of periplasmic enzymes from Escherichia coli by penicillin-ethylenediaminetetraacetate treatment.", "content": "When Escherichia coli cells are converted into spheroplasts by penicillin treatment, none of the periplasmic enzymes is released. However, incubation of the penicillin-induced spheroplasts in a medium containing ethylenediaminetetraacetic acid caused the release of endonuclease I and cyclic phosphodiesterase but not of beta-galactosidase.", "contents": "Release of periplasmic enzymes from Escherichia coli by penicillin-ethylenediaminetetraacetate treatment. When Escherichia coli cells are converted into spheroplasts by penicillin treatment, none of the periplasmic enzymes is released. However, incubation of the penicillin-induced spheroplasts in a medium containing ethylenediaminetetraacetic acid caused the release of endonuclease I and cyclic phosphodiesterase but not of beta-galactosidase."}
{"id": "PMID:195933", "title": "Spore coat protein and enterotoxin synthesis in Clostridium perfringens.", "content": "Polyacrylamide gel profiles of Clostridium perfringens spore coat protein revealed four and occasionally five components. Pulse-chase experiments indicated that synthesis of coat protein polypeptide and enterotoxin was an early sporulation event. However, maximum synthesis occurred coincident with the onset of heat resistance.", "contents": "Spore coat protein and enterotoxin synthesis in Clostridium perfringens. Polyacrylamide gel profiles of Clostridium perfringens spore coat protein revealed four and occasionally five components. Pulse-chase experiments indicated that synthesis of coat protein polypeptide and enterotoxin was an early sporulation event. However, maximum synthesis occurred coincident with the onset of heat resistance."}
{"id": "PMID:195934", "title": "A specific method for the determination of threonine in rat blood plasma using aldehyde dehydrogenase.", "content": "A simple and sensitive method for the determination of threonine in rat blood plasma using aldehyde dehydrogenase after oxidation with periodate was developed. By the present method, threonine could be completely discriminated from serine and determined at the nanomole level. The amount of threonine in rat blood plasma obtained by the present method coincided well with the value determined on an amino acid analyzer.", "contents": "A specific method for the determination of threonine in rat blood plasma using aldehyde dehydrogenase. A simple and sensitive method for the determination of threonine in rat blood plasma using aldehyde dehydrogenase after oxidation with periodate was developed. By the present method, threonine could be completely discriminated from serine and determined at the nanomole level. The amount of threonine in rat blood plasma obtained by the present method coincided well with the value determined on an amino acid analyzer."}
{"id": "PMID:195936", "title": "The sulfhydryl groups involved in the active site of myosin B adenosinetriphosphatase. II. Effect of modification of the Sa thiol group on superprecipitation and clearing.", "content": "The effect of Sa modification with NEM, which activates Mg2+-ATPase through an enhancement of the association of actin and myosin, was investigated on the superprecipitation, clearing and Mg2+-ITPase of myosin B with reference to the effect of S1-blocking. 1. Superprecipitation induced by ATP was markedly enhanced by Sa-blocking even at high concentrations of Mg2+ and substrate; this may be due to an increase in the affinity of myosin and actin on blocking Sa. 2. Nevertheless, neither ITP-induced superprecipitation nor Mg2+-ITPase was affected by Sa modification. 3. Blocking of S1 brought about the inhibition of ATP- and ITP-induced superprecipitation and Mg2+-ITPase activity, suggesting that S1-blocking decreases the affinity of myosin and actin. 4. Sa-blocked myosin B showed greater resistance to clearing by ATP, especially in the presence of Ca2+ ions, whereas in the clearing response of actomyosin gel to PPi no difference between Sa-blocked and unmodified myosins B was observed. On the other hand, the clearing response of myosin B became more sensitive to both ATP and PPi on blocking S1. Based on the above results and preliminary data suggesting that Sa is located in LMM, the interaction of myosin filaments and actin filaments under physiological conditions is discussed.", "contents": "The sulfhydryl groups involved in the active site of myosin B adenosinetriphosphatase. II. Effect of modification of the Sa thiol group on superprecipitation and clearing. The effect of Sa modification with NEM, which activates Mg2+-ATPase through an enhancement of the association of actin and myosin, was investigated on the superprecipitation, clearing and Mg2+-ITPase of myosin B with reference to the effect of S1-blocking. 1. Superprecipitation induced by ATP was markedly enhanced by Sa-blocking even at high concentrations of Mg2+ and substrate; this may be due to an increase in the affinity of myosin and actin on blocking Sa. 2. Nevertheless, neither ITP-induced superprecipitation nor Mg2+-ITPase was affected by Sa modification. 3. Blocking of S1 brought about the inhibition of ATP- and ITP-induced superprecipitation and Mg2+-ITPase activity, suggesting that S1-blocking decreases the affinity of myosin and actin. 4. Sa-blocked myosin B showed greater resistance to clearing by ATP, especially in the presence of Ca2+ ions, whereas in the clearing response of actomyosin gel to PPi no difference between Sa-blocked and unmodified myosins B was observed. On the other hand, the clearing response of myosin B became more sensitive to both ATP and PPi on blocking S1. Based on the above results and preliminary data suggesting that Sa is located in LMM, the interaction of myosin filaments and actin filaments under physiological conditions is discussed."}
{"id": "PMID:195937", "title": "Proteolysis of apoproteins in human serum low density lipoprotein.", "content": "Proteolytic treatment of human serum low density lipoprotein (LDL) resulted in the observation of interesting time-dependent changes in the sodium dodecyl sulfate-polyacrylamide gel electrophoretic pattern of apo-LDL. Five major fragments with well-defined relative mobilities appeared within 30 min of protease treatment. Prolonged treatment with subtilisin caused changes in the amount of peptides in each of the five bands but their positions on the gel remained unchanged. Periodic acid-Schiff base staining of the gel showed a proteolytic fragment with an apparent molecular weight of 110.000 (actually a cross-linked dimer of two peptides with molecular weights of 77,000 and 68,000) to be a carbohydrate-bearing peptide that was most resistant to further proteolysis and therefore responsible for the interaction between the digested LDL and concanavalin A.", "contents": "Proteolysis of apoproteins in human serum low density lipoprotein. Proteolytic treatment of human serum low density lipoprotein (LDL) resulted in the observation of interesting time-dependent changes in the sodium dodecyl sulfate-polyacrylamide gel electrophoretic pattern of apo-LDL. Five major fragments with well-defined relative mobilities appeared within 30 min of protease treatment. Prolonged treatment with subtilisin caused changes in the amount of peptides in each of the five bands but their positions on the gel remained unchanged. Periodic acid-Schiff base staining of the gel showed a proteolytic fragment with an apparent molecular weight of 110.000 (actually a cross-linked dimer of two peptides with molecular weights of 77,000 and 68,000) to be a carbohydrate-bearing peptide that was most resistant to further proteolysis and therefore responsible for the interaction between the digested LDL and concanavalin A."}
{"id": "PMID:195938", "title": "Effects of purine nucleotides on photosynthetic electron transport in isolated chloroplasts.", "content": "The effects of guanylates and inosinates (and adenylates) on phosphorylation, ferricyanide reduction, and light-induced H+ uptake in spinach chloroplasts were studied. GDP, GTP, IDP, and ITP (but not GMP and IMP) stimulated the light-induced H+ uptake and partially inhibited ferricyanide reduction. Phosphate, arsenate, and phlorizin increased the extent of inhibition by these nucleotides and decreased the values of their apparent dissociation constants for the inhibition process. In the presence of phosphate (or arsenate), restoration of ferricyanide reduction from the level inhibited by guanylates and inosinates was observed as phosphorylation (or arsenylation) proceeded. These results suggest that phosphorylation of GDP and IDP as well as ADP takes place after two steps of nucleotide binding to the chloroplast coupling factor 1. The apparent dissociation constants of GDP and IDP for these two binding steps were estimated to be about 34 and 38 muM for the first and 110 and 160 muM for the second step, respectively (at pH 8.3, 15 degrees C). Above pH9, the ratio (P/delta-e) of the extent of phosphorylation to the increment of electron transport from the basal level measured in the presence of [ATP + Pi] or [ADP + Pi+ phlorizin], became increasingly large. When the electron transport level inhibited by dicyclohexyl-carbodiimide was taken to be the basal activity, the P/delta-e ratio remained almost constant (approximately 1) from pH 7.0 up to 10.", "contents": "Effects of purine nucleotides on photosynthetic electron transport in isolated chloroplasts. The effects of guanylates and inosinates (and adenylates) on phosphorylation, ferricyanide reduction, and light-induced H+ uptake in spinach chloroplasts were studied. GDP, GTP, IDP, and ITP (but not GMP and IMP) stimulated the light-induced H+ uptake and partially inhibited ferricyanide reduction. Phosphate, arsenate, and phlorizin increased the extent of inhibition by these nucleotides and decreased the values of their apparent dissociation constants for the inhibition process. In the presence of phosphate (or arsenate), restoration of ferricyanide reduction from the level inhibited by guanylates and inosinates was observed as phosphorylation (or arsenylation) proceeded. These results suggest that phosphorylation of GDP and IDP as well as ADP takes place after two steps of nucleotide binding to the chloroplast coupling factor 1. The apparent dissociation constants of GDP and IDP for these two binding steps were estimated to be about 34 and 38 muM for the first and 110 and 160 muM for the second step, respectively (at pH 8.3, 15 degrees C). Above pH9, the ratio (P/delta-e) of the extent of phosphorylation to the increment of electron transport from the basal level measured in the presence of [ATP + Pi] or [ADP + Pi+ phlorizin], became increasingly large. When the electron transport level inhibited by dicyclohexyl-carbodiimide was taken to be the basal activity, the P/delta-e ratio remained almost constant (approximately 1) from pH 7.0 up to 10."}
{"id": "PMID:195940", "title": "A novel nuclear relaxation approach for estimating distance between enzyme- and nucleotide-bound metal ions at the catalytic site of pyruvate kinase.", "content": "This communication introduces a nuclear relaxation approach for an estimation of the distance between two paramagnetic metal ion sites on a metal-activated enzyme. The method is based on the existence of an exchange of unpaired electron spin magnetizations between the two metals via energy-conserving concerted mutual spin flips which arise from time-dependent dipolar interactions of the electronic magnetizations. This cross-relaxation of electronic magnetizations depends on the inverse sixth power of the intermetal distance and may, under suitable conditions, affect the longitudinal relaxation rate of inner sphere water protons by altering the electron-proton dipolar correlation time when the latter is dominated by electron spin relaxation. The technique is applied to estimate the distance of 5.2 +/- 0.9 A between Mn2+ and Cr3+ in the pyruvate kinase-Mn2+-ATPCr3+ complex and indicates the existence of a van der Waals contact between the hydration spheres of the enzyme- and nucleotide-bound metal ions.", "contents": "A novel nuclear relaxation approach for estimating distance between enzyme- and nucleotide-bound metal ions at the catalytic site of pyruvate kinase. This communication introduces a nuclear relaxation approach for an estimation of the distance between two paramagnetic metal ion sites on a metal-activated enzyme. The method is based on the existence of an exchange of unpaired electron spin magnetizations between the two metals via energy-conserving concerted mutual spin flips which arise from time-dependent dipolar interactions of the electronic magnetizations. This cross-relaxation of electronic magnetizations depends on the inverse sixth power of the intermetal distance and may, under suitable conditions, affect the longitudinal relaxation rate of inner sphere water protons by altering the electron-proton dipolar correlation time when the latter is dominated by electron spin relaxation. The technique is applied to estimate the distance of 5.2 +/- 0.9 A between Mn2+ and Cr3+ in the pyruvate kinase-Mn2+-ATPCr3+ complex and indicates the existence of a van der Waals contact between the hydration spheres of the enzyme- and nucleotide-bound metal ions."}
{"id": "PMID:195941", "title": "Inhibition by lead ion of Electrophorus electroplax (Na+ + K+)-adenosine triphosphatase and K+-p-nitrophenylphosphatase.", "content": "Inorganic lead ion in micromolar concentrations inhibits Electrophorus electroplax microsomal (Na+ + K+)-adenosine triphosphatase ((Na+ + K+)-ATPase) and K+-p-nitrophenylphosphatase (NPPase). Under the same conditions, the same concentrations of PbCl2 that inhibit ATPase activity also stimulate the phosphorylation of electroplax microsomes in the absence of added Na+. Enzyme activity is protected from inhibition by increasing concentrations of microsomes, ATP, and other metal ion chelators. The kinetics follow the pattern of a reversible noncompetitive inhibitor. No kinetic evidence is elicited for interactions of Pb2+ with Na+, K+, Mg2+, ATP, or p-nitrophenylphosphate. Na+- ATPase, in the absence of K+, and (Na+ + K+)-NPPase activity at low [K+] are also inhibited. ATP inhibition of NPPase is not reversed by Pb2+. The calculated concentrations of free [Pb2+] that produce 50% inhibition are similar for ATPase and NPPase activities. Pb2+ may act at a single independent binding site to produce both stimulation of the kinase and inhibition of the phosphatase activities.", "contents": "Inhibition by lead ion of Electrophorus electroplax (Na+ + K+)-adenosine triphosphatase and K+-p-nitrophenylphosphatase. Inorganic lead ion in micromolar concentrations inhibits Electrophorus electroplax microsomal (Na+ + K+)-adenosine triphosphatase ((Na+ + K+)-ATPase) and K+-p-nitrophenylphosphatase (NPPase). Under the same conditions, the same concentrations of PbCl2 that inhibit ATPase activity also stimulate the phosphorylation of electroplax microsomes in the absence of added Na+. Enzyme activity is protected from inhibition by increasing concentrations of microsomes, ATP, and other metal ion chelators. The kinetics follow the pattern of a reversible noncompetitive inhibitor. No kinetic evidence is elicited for interactions of Pb2+ with Na+, K+, Mg2+, ATP, or p-nitrophenylphosphate. Na+- ATPase, in the absence of K+, and (Na+ + K+)-NPPase activity at low [K+] are also inhibited. ATP inhibition of NPPase is not reversed by Pb2+. The calculated concentrations of free [Pb2+] that produce 50% inhibition are similar for ATPase and NPPase activities. Pb2+ may act at a single independent binding site to produce both stimulation of the kinase and inhibition of the phosphatase activities."}
{"id": "PMID:195942", "title": "Substrate and effector specificity of a guanosine 3':5'-monophosphate phosphodiesterase from rat liver.", "content": "Guanosine 3':5'-monophosphate phosphodiesterases, which appear to be under allosteric control, have been partially purified from rat liver supernatant and particulate fractions. The preferred substrate for both phosphodiesterases was cGMP (Km values: cGMP less than cIMP less than cAMP). At subsaturating concentrations of substrate, the phosphodiesterases were stimulated by purine cyclic nucleotides. The order of effectiveness for activation of cyclic nucleotide hydrolysis was cGMP greater than cIMP greater than cAMP greater than cXMP. Using cAMP derivatives as activators of cIMP hydrolysis, modifications in the ribose, cyclic phosphate, and purine moieties were shown to alter the ability of the cyclic nucleotide to activate the supernatant enzyme. cGMP, at concentrations that stimulated cyclic nucleotide hydrolysis, enhanced chymotryptic inactivation of the supernatant phosphodiesterase. At similar concentrations, cAMP was not effective. It appears that on interaction with appropriate cyclic nucleotides, this phosphodiesterase undergoes conformational changes that are associated with increased catalytic activity and enhanced susceptibility to proteolytic attack. Divalent cation may not be required for the nucleotide-phosphodiesterase interaction and resultant change in conformation.", "contents": "Substrate and effector specificity of a guanosine 3':5'-monophosphate phosphodiesterase from rat liver. Guanosine 3':5'-monophosphate phosphodiesterases, which appear to be under allosteric control, have been partially purified from rat liver supernatant and particulate fractions. The preferred substrate for both phosphodiesterases was cGMP (Km values: cGMP less than cIMP less than cAMP). At subsaturating concentrations of substrate, the phosphodiesterases were stimulated by purine cyclic nucleotides. The order of effectiveness for activation of cyclic nucleotide hydrolysis was cGMP greater than cIMP greater than cAMP greater than cXMP. Using cAMP derivatives as activators of cIMP hydrolysis, modifications in the ribose, cyclic phosphate, and purine moieties were shown to alter the ability of the cyclic nucleotide to activate the supernatant enzyme. cGMP, at concentrations that stimulated cyclic nucleotide hydrolysis, enhanced chymotryptic inactivation of the supernatant phosphodiesterase. At similar concentrations, cAMP was not effective. It appears that on interaction with appropriate cyclic nucleotides, this phosphodiesterase undergoes conformational changes that are associated with increased catalytic activity and enhanced susceptibility to proteolytic attack. Divalent cation may not be required for the nucleotide-phosphodiesterase interaction and resultant change in conformation."}
{"id": "PMID:195943", "title": "Synthesis of plasma lipoproteins by the isolated perfused liver from the fasted and fed pig.", "content": "Livers from fasted or fed pigs were perfused for 5 h with Krebs-Ringer bicarbonate buffer containing human erythrocytes, bovine serum albumin, glucose, and amino acids. Liver viability was estimated by color, consistency, portal pressure, bile flow, electrolyte changes, and glucose levels in the perfusate, urea synthesis, [1-14C]leucine incorporation into protein, oxygen uptake, and histological examination. It was shown that the liver was maintained in good condition throughout the perfusions. The apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I) in the perfusate were measured by solid phase radioimmunoassay. In the fasted state, the amount of apoB released was greatest in the low density lipoprotein (LDL) fraction and the amount was especially high during the 1st h. There was no increase of apoB in this fraction by feeding. The apoB in the very low density lipoprotein (VLDL) fraction was less than that in the LDL fraction in the fasted state, and it increased more than 2-fold in the fed animals. The amount of apoA-I was greatest in the 1.21 bottom fraction and was relatively small in the high density lipoprotein (HDL) fraction. The HDL fraction contained approximately one-twentieth as much apoA-I as the 1.21 bottom fraction in the fasted condition. In the fed state, apoA-I in the HDL fraction increased markedly, although the amount was still less than in the 1.21 bottom fraction.", "contents": "Synthesis of plasma lipoproteins by the isolated perfused liver from the fasted and fed pig. Livers from fasted or fed pigs were perfused for 5 h with Krebs-Ringer bicarbonate buffer containing human erythrocytes, bovine serum albumin, glucose, and amino acids. Liver viability was estimated by color, consistency, portal pressure, bile flow, electrolyte changes, and glucose levels in the perfusate, urea synthesis, [1-14C]leucine incorporation into protein, oxygen uptake, and histological examination. It was shown that the liver was maintained in good condition throughout the perfusions. The apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I) in the perfusate were measured by solid phase radioimmunoassay. In the fasted state, the amount of apoB released was greatest in the low density lipoprotein (LDL) fraction and the amount was especially high during the 1st h. There was no increase of apoB in this fraction by feeding. The apoB in the very low density lipoprotein (VLDL) fraction was less than that in the LDL fraction in the fasted state, and it increased more than 2-fold in the fed animals. The amount of apoA-I was greatest in the 1.21 bottom fraction and was relatively small in the high density lipoprotein (HDL) fraction. The HDL fraction contained approximately one-twentieth as much apoA-I as the 1.21 bottom fraction in the fasted condition. In the fed state, apoA-I in the HDL fraction increased markedly, although the amount was still less than in the 1.21 bottom fraction."}
{"id": "PMID:195946", "title": "Regulation of protein degradation in normal and transformed human cells. Effects of growth state, medium composition, and viral transformation.", "content": "In WI-38, a normal human fibroblast, the rates of degradation of short lived and long lived proteins are identical whether the cultures are growing exponentially or are density-inhibited. Replacement of the growth medium with fresh medium does not alter these rates. In VA-13, an SV-40 transformed derivative of WI-38, the rates of protein degradation are also independent of growth rate and fresh medium. However, in both WI-38 and VA-13 the rate of long lived protein degradation increases as the serum concentration is reduced below 5%. After complete serum withdrawal, the rate increases by 60 to 100% in both cell types. Withdrawal of arginine and phenylalanine triples the rate of long lived protein degradation, while addition of 10% dialyzed serum to this amino acid-deficient medium reduces the effect to twice that of the controls. Incubation of both types of cells in phosphate-buffered saline also increases protein degradation. This effect is reduced by glucose, albumin, and dialyzed serum. Therefore, the rate of protein degradation is independent of growth rate in normal and transformed human cells. However, the rate of degradation is closely coupled to certain medium alterations.", "contents": "Regulation of protein degradation in normal and transformed human cells. Effects of growth state, medium composition, and viral transformation. In WI-38, a normal human fibroblast, the rates of degradation of short lived and long lived proteins are identical whether the cultures are growing exponentially or are density-inhibited. Replacement of the growth medium with fresh medium does not alter these rates. In VA-13, an SV-40 transformed derivative of WI-38, the rates of protein degradation are also independent of growth rate and fresh medium. However, in both WI-38 and VA-13 the rate of long lived protein degradation increases as the serum concentration is reduced below 5%. After complete serum withdrawal, the rate increases by 60 to 100% in both cell types. Withdrawal of arginine and phenylalanine triples the rate of long lived protein degradation, while addition of 10% dialyzed serum to this amino acid-deficient medium reduces the effect to twice that of the controls. Incubation of both types of cells in phosphate-buffered saline also increases protein degradation. This effect is reduced by glucose, albumin, and dialyzed serum. Therefore, the rate of protein degradation is independent of growth rate in normal and transformed human cells. However, the rate of degradation is closely coupled to certain medium alterations."}
{"id": "PMID:195948", "title": "Purineless death: ribosomal RNA turnover in a purine-starved ade- mutant of Chinese hamster cells.", "content": "When V79 pur 1, a purine-requiring auxotroph of a Chinese hamster cell line, is deprived of adenine, nucleic acid and protein synthesis decline rapidly. However, on continuous starvation RNA and DNA synthesis recommences to reach approximately 30% of the normal level between 12 to 24 h starvation. This is accompanied by a rise in the intracellular nucleotide pool. Utilizing mengovirus, which gives a productive infection in V79 pur 1 cells even under conditions of starvation, we can show that rRNA is preferentially degraded and provides the nucleotides for RNA synthesis. Thus \"purineless\" death in mammalian cells is accompanied by turnover of stable RNA.", "contents": "Purineless death: ribosomal RNA turnover in a purine-starved ade- mutant of Chinese hamster cells. When V79 pur 1, a purine-requiring auxotroph of a Chinese hamster cell line, is deprived of adenine, nucleic acid and protein synthesis decline rapidly. However, on continuous starvation RNA and DNA synthesis recommences to reach approximately 30% of the normal level between 12 to 24 h starvation. This is accompanied by a rise in the intracellular nucleotide pool. Utilizing mengovirus, which gives a productive infection in V79 pur 1 cells even under conditions of starvation, we can show that rRNA is preferentially degraded and provides the nucleotides for RNA synthesis. Thus \"purineless\" death in mammalian cells is accompanied by turnover of stable RNA."}
{"id": "PMID:195949", "title": "Protein kinases in brown adipose tissue of developing rats. Electrophoretic separation and assay of soluble protein kinases on polyacrylamide gels and a study of their properties and changes during development.", "content": "Protein kinase activity was detected and assayed directly on polyacrylamide gels after disc electrophoresis of the 100,000 X g supernatant fraction of brown adipose tissue of infant rats. Nine major bands of activity were detected, eight of which could be stimulated by cAMP or inhibited by the cAMP-dependent protein kinase inhibitor protein. This electrophoretic technique revealed heterogeneity in the cAMP-dependent protein kinase activity eluted from DEAE-cellulose by high concentrations of salt, but not in the peak of activity eluted by low concentrations of salt. The catalytic properties and substrate specificities of the kinases in the various bands were studied while the enzymes were still in the gels. The activity in each band differed from each of the others in at least one of these properties. The activities of the protein kinases in brown fat changed as the animals grew, and each band exhibited a distinct and unique developmental pattern. The major changes in kinase activities occurred in the immediate post-parturition period, then at 15 days after birth and at weaning. These developmental stages coincide with the periods during which the tissue undergoes changes in the rate of its proliferation, differentiation, and functional activity.", "contents": "Protein kinases in brown adipose tissue of developing rats. Electrophoretic separation and assay of soluble protein kinases on polyacrylamide gels and a study of their properties and changes during development. Protein kinase activity was detected and assayed directly on polyacrylamide gels after disc electrophoresis of the 100,000 X g supernatant fraction of brown adipose tissue of infant rats. Nine major bands of activity were detected, eight of which could be stimulated by cAMP or inhibited by the cAMP-dependent protein kinase inhibitor protein. This electrophoretic technique revealed heterogeneity in the cAMP-dependent protein kinase activity eluted from DEAE-cellulose by high concentrations of salt, but not in the peak of activity eluted by low concentrations of salt. The catalytic properties and substrate specificities of the kinases in the various bands were studied while the enzymes were still in the gels. The activity in each band differed from each of the others in at least one of these properties. The activities of the protein kinases in brown fat changed as the animals grew, and each band exhibited a distinct and unique developmental pattern. The major changes in kinase activities occurred in the immediate post-parturition period, then at 15 days after birth and at weaning. These developmental stages coincide with the periods during which the tissue undergoes changes in the rate of its proliferation, differentiation, and functional activity."}
{"id": "PMID:195953", "title": "5-Methylcytosine content of rat hepatoma DNA substituted with bromodeoxyuridine.", "content": "The aim of these experiments was to test whether incorporation of bromodeoxyuridine into DNA affects DNA methylation. Rat hepatoma (HTC) cells in culture were labeled for two generations with [14C]bromodeoxyuridine and [3H]thymidine to yield DNA which was 2.1, 20.6, 52.6, and 95.0% bromodeoxyuridine-substituted in the newly made strands. The DNA then was fractionated into highly repetitive, moderately repetitive, and single copy sequences. As determined by a comparison of 14C and 3H counts per min, the percentage of substitution with bromodeoxyuridine was found to be the same in each repetition class. The 5-methylcytosine content of each fraction was determined using high pressure liquid chromatography. It was found that bromodeoxyuridine, even at a level of substitution into newly mad DNA of 95%, has no effect on the 5-methylcytosine content of DNA. At all levels of bromodeoxyuridine substitution, highly repetitive DNA has slightly more 5-methylcytosine (3.0% of total cytosine) than does single copy DNA or moderately repetitive DNA (2.3%). The 5-methylcytosine content of whole HTC DNA is the same as that of rat liver DNA (2.4%).", "contents": "5-Methylcytosine content of rat hepatoma DNA substituted with bromodeoxyuridine. The aim of these experiments was to test whether incorporation of bromodeoxyuridine into DNA affects DNA methylation. Rat hepatoma (HTC) cells in culture were labeled for two generations with [14C]bromodeoxyuridine and [3H]thymidine to yield DNA which was 2.1, 20.6, 52.6, and 95.0% bromodeoxyuridine-substituted in the newly made strands. The DNA then was fractionated into highly repetitive, moderately repetitive, and single copy sequences. As determined by a comparison of 14C and 3H counts per min, the percentage of substitution with bromodeoxyuridine was found to be the same in each repetition class. The 5-methylcytosine content of each fraction was determined using high pressure liquid chromatography. It was found that bromodeoxyuridine, even at a level of substitution into newly mad DNA of 95%, has no effect on the 5-methylcytosine content of DNA. At all levels of bromodeoxyuridine substitution, highly repetitive DNA has slightly more 5-methylcytosine (3.0% of total cytosine) than does single copy DNA or moderately repetitive DNA (2.3%). The 5-methylcytosine content of whole HTC DNA is the same as that of rat liver DNA (2.4%)."}
{"id": "PMID:195954", "title": "Crystallographic data for chicken liver fructose bisphosphatase.", "content": "Large, single crystals of fructose bisphosphatase have been obtained under a variety of conditions. Preliminary crystallographic analysis reveals that the space group is R3, the cell dimensions on the hexagonal axes are a = b = 304 A and c = 80.4 A, and there is one tetramer per asymmetric unit.", "contents": "Crystallographic data for chicken liver fructose bisphosphatase. Large, single crystals of fructose bisphosphatase have been obtained under a variety of conditions. Preliminary crystallographic analysis reveals that the space group is R3, the cell dimensions on the hexagonal axes are a = b = 304 A and c = 80.4 A, and there is one tetramer per asymmetric unit."}
{"id": "PMID:195956", "title": "Ca2+-dependent regulation of cyclic-AMP phosphodiesterase by parvalbumin.", "content": "Carp parvalbumin has been shown to activate rat brain phosphodiesterase in a Ca2+-dependent manner. The concentration of Ca2+ required for half-maximal stimulation is 1.4 X 10(-7) M, whereas rat testis Ca2+-dependent regulator (CDR) of phosphodiesterase required 1.2 X 10(-6) M Ca2+. The difference in the slopes of the two curves demonstrated that the activation induced by parvalbumin was not the result of a small contamination by CDR. In addition, it has been shown that Ca2+ binding to parvalbumin parallels its activation of phosphodiesterase. These data suggest that Ca2+ must bind to a single specific metal binding site before phosphodiesterase can be fully activated.", "contents": "Ca2+-dependent regulation of cyclic-AMP phosphodiesterase by parvalbumin. Carp parvalbumin has been shown to activate rat brain phosphodiesterase in a Ca2+-dependent manner. The concentration of Ca2+ required for half-maximal stimulation is 1.4 X 10(-7) M, whereas rat testis Ca2+-dependent regulator (CDR) of phosphodiesterase required 1.2 X 10(-6) M Ca2+. The difference in the slopes of the two curves demonstrated that the activation induced by parvalbumin was not the result of a small contamination by CDR. In addition, it has been shown that Ca2+ binding to parvalbumin parallels its activation of phosphodiesterase. These data suggest that Ca2+ must bind to a single specific metal binding site before phosphodiesterase can be fully activated."}
{"id": "PMID:195958", "title": "The role of 2,4,5-trihydroxyphenylalanine in melanin biosynthesis.", "content": "Both 3,4-dihydroxyphenylalanine and 2,4,5-trihydroxyphenylalanine were oxidized with periodate and mushroom tyrosinase to determine whether the latter compound is an intermediate in melanin biosynthesis. Matrix analysis of the spectra obtained with a rapid scan spectrophotometer and comparison of the spectra of quinone intermediates with model quinones disclosed that, although 2,4,5-trihydroxyphenylalanine can be oxidized to 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome), this oxidation proceeds through a stable intermediate, 5-(2-carboxy-2-aminoethyl)-2-hydroxy-1,4-benzoquinone, which does not appear in the oxidation of 3,4-dihydroxyphenylalanine to dopachrome. Thus, these studies are in agreement with the original postulate, that 4-(2-carboxy-2-aminoethyl)-1,2-benzoquinone and leukodopachrome are the intermediates in the major pathway for dopachrome synthesis.", "contents": "The role of 2,4,5-trihydroxyphenylalanine in melanin biosynthesis. Both 3,4-dihydroxyphenylalanine and 2,4,5-trihydroxyphenylalanine were oxidized with periodate and mushroom tyrosinase to determine whether the latter compound is an intermediate in melanin biosynthesis. Matrix analysis of the spectra obtained with a rapid scan spectrophotometer and comparison of the spectra of quinone intermediates with model quinones disclosed that, although 2,4,5-trihydroxyphenylalanine can be oxidized to 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome), this oxidation proceeds through a stable intermediate, 5-(2-carboxy-2-aminoethyl)-2-hydroxy-1,4-benzoquinone, which does not appear in the oxidation of 3,4-dihydroxyphenylalanine to dopachrome. Thus, these studies are in agreement with the original postulate, that 4-(2-carboxy-2-aminoethyl)-1,2-benzoquinone and leukodopachrome are the intermediates in the major pathway for dopachrome synthesis."}
{"id": "PMID:195959", "title": "Self-association of apo-C-I from the human high density lipoprotein complex.", "content": "The molecular properties of apo-C-I, isolated from the human high density lipoprotein complex, have been evaluated as a function of pH, solvent composition, and protein concentration by sedimentation equilibrium and circular dichroic measurements. This protein self-associates in aqueous solution at neutral pH with concomitant changes in secondary structure. In contrast, in the acid pH range, apo-C-I is monomeric and its ellipticity is independent of protein concentration. The results are discussed in terms of the interpretation of experiments where changes in the physical properties of apolipoproteins have been used to monitor ligand binding and lipid-apolipoprotein recombination.", "contents": "Self-association of apo-C-I from the human high density lipoprotein complex. The molecular properties of apo-C-I, isolated from the human high density lipoprotein complex, have been evaluated as a function of pH, solvent composition, and protein concentration by sedimentation equilibrium and circular dichroic measurements. This protein self-associates in aqueous solution at neutral pH with concomitant changes in secondary structure. In contrast, in the acid pH range, apo-C-I is monomeric and its ellipticity is independent of protein concentration. The results are discussed in terms of the interpretation of experiments where changes in the physical properties of apolipoproteins have been used to monitor ligand binding and lipid-apolipoprotein recombination."}
{"id": "PMID:195963", "title": "Envelope composition and antibiotic hypersensitivity of Escherichia coli mutants defective in phosphatidylserine synthetase.", "content": "Mutants of Escherichia coli K12, defective in phosphatidylserine synthetase (pss), can be isolated as temperature-sensitive, conditional lethals. When cultivated at intermediate temperatures (30 degrees), such mutants contain approximately 3 times more phosphatidylglycerol plus cardiolipin (and less phosphatidylethanolamine) than normal. We now wish to report that, under these conditions, the pss-8 mutant is hypersensitive to certain antibiotics, especially to streptomycin, kanamycin, and gentamicin, although also to ampicillin and novobiocin. At 30 degrees, the membrane protein and fatty acid composition of pss-8 is nearly normal, i.e. identical with an isogenic pss+ organism. Radiochemical labeling and bacteriophage growth studies show that lipopolysaccharide is also unaltered. Therefore, the antibiotic hypersensitivity of pss-8 differs from previously reported hypersensitivities, associated with lipopolysaccharide defects. These results suggest that the polar phospholipid headgroups may play an important role in maintaining the barrier function of the outer gramnegative membrane and that putative inhibitors of the phosphatidylserine synthetase might potentiate the action of numerous antibiotics currently in clinical use.", "contents": "Envelope composition and antibiotic hypersensitivity of Escherichia coli mutants defective in phosphatidylserine synthetase. Mutants of Escherichia coli K12, defective in phosphatidylserine synthetase (pss), can be isolated as temperature-sensitive, conditional lethals. When cultivated at intermediate temperatures (30 degrees), such mutants contain approximately 3 times more phosphatidylglycerol plus cardiolipin (and less phosphatidylethanolamine) than normal. We now wish to report that, under these conditions, the pss-8 mutant is hypersensitive to certain antibiotics, especially to streptomycin, kanamycin, and gentamicin, although also to ampicillin and novobiocin. At 30 degrees, the membrane protein and fatty acid composition of pss-8 is nearly normal, i.e. identical with an isogenic pss+ organism. Radiochemical labeling and bacteriophage growth studies show that lipopolysaccharide is also unaltered. Therefore, the antibiotic hypersensitivity of pss-8 differs from previously reported hypersensitivities, associated with lipopolysaccharide defects. These results suggest that the polar phospholipid headgroups may play an important role in maintaining the barrier function of the outer gramnegative membrane and that putative inhibitors of the phosphatidylserine synthetase might potentiate the action of numerous antibiotics currently in clinical use."}
{"id": "PMID:195964", "title": "Binding of viral glycoprotein mRNA to endoplasmic reticulum membranes is disrupted by puromycin.", "content": "Previous studies showed that the glycoprotein (G) of vesicular stomatitis virus is synthesized in association with the endoplasmic reticulum (ER) membrane and that all G mRNA co-fractionates with ER membrane. Here, we show that treatment of infected cells with puromycin results in dissociation of G mRNA, and presumably the associated ribosomes, from the ER membrane. Even it extracts from treated cells are kept at low ionic strength (0.01 M KCl), over 80% of G mRNA is found unattached to membranes. There is no evidence for direct interaction of GmRNA with membranes; rather, the linkage apparently is mediated by the nascent G polypeptide.", "contents": "Binding of viral glycoprotein mRNA to endoplasmic reticulum membranes is disrupted by puromycin. Previous studies showed that the glycoprotein (G) of vesicular stomatitis virus is synthesized in association with the endoplasmic reticulum (ER) membrane and that all G mRNA co-fractionates with ER membrane. Here, we show that treatment of infected cells with puromycin results in dissociation of G mRNA, and presumably the associated ribosomes, from the ER membrane. Even it extracts from treated cells are kept at low ionic strength (0.01 M KCl), over 80% of G mRNA is found unattached to membranes. There is no evidence for direct interaction of GmRNA with membranes; rather, the linkage apparently is mediated by the nascent G polypeptide."}
{"id": "PMID:195965", "title": "Binding of [3H]oxytocin to cells isolated from the mammary gland of the lactating rat.", "content": "More than 90 percent of the cells isolated from the mammary gland of lactating rats with 0.1 percent collagenase were viable by dye exclusion. Myoepithelial cells comprised about one-third of the mammary cells and appeared to be morphologically intact in electron micrographs. [(3)H]Oxytocin-binding activity was localized in an enriched myoepitheial cell fraction obtained by density gradient centrifugation of the isolated cells. The amount of [(3)H] oxytocin bound at 20 degree C and pH 7.6 was proportional to the concentration of oxytocin and the number of cells, reaching a steady state by 40 min. About 0.45 fmol of oxytocin were bound per 10(6) cells. There was a single class of independent binding sites with an apparent K(d), estimated from equilibrium conditions, of 5 nM. This value agrees within experimental error with the value calculated from the ratio of reverse to forward rate constants (5.8 x 10(-4)s(-1) and 2.2 x 10(5) M(-1)s(-1), respectively), consistent with a single-step model for the interaction of oxytocin with binding sites on the cells. Erythrocytes bound only 3.5 percent of the amount of oxytocin bound by an equal number of mammary cells. Oxytocin analogues competed with [(3)H]oxytocin for binding sites in the following order: [deamino]oxytocin > [4-threonine]oxytocin > oxytocin > [O- methyltyrosine]oxytocin > [8-lysine]vasopressin; [lysine]-bradykinin and [4-proline]oxytocin were not inhibitory in the dose ranges tested. These results demonstrate that isolated mammary cells possess oxytocin receptors with properties comparable to those found in broken mammary cell preparations.", "contents": "Binding of [3H]oxytocin to cells isolated from the mammary gland of the lactating rat. More than 90 percent of the cells isolated from the mammary gland of lactating rats with 0.1 percent collagenase were viable by dye exclusion. Myoepithelial cells comprised about one-third of the mammary cells and appeared to be morphologically intact in electron micrographs. [(3)H]Oxytocin-binding activity was localized in an enriched myoepitheial cell fraction obtained by density gradient centrifugation of the isolated cells. The amount of [(3)H] oxytocin bound at 20 degree C and pH 7.6 was proportional to the concentration of oxytocin and the number of cells, reaching a steady state by 40 min. About 0.45 fmol of oxytocin were bound per 10(6) cells. There was a single class of independent binding sites with an apparent K(d), estimated from equilibrium conditions, of 5 nM. This value agrees within experimental error with the value calculated from the ratio of reverse to forward rate constants (5.8 x 10(-4)s(-1) and 2.2 x 10(5) M(-1)s(-1), respectively), consistent with a single-step model for the interaction of oxytocin with binding sites on the cells. Erythrocytes bound only 3.5 percent of the amount of oxytocin bound by an equal number of mammary cells. Oxytocin analogues competed with [(3)H]oxytocin for binding sites in the following order: [deamino]oxytocin > [4-threonine]oxytocin > oxytocin > [O- methyltyrosine]oxytocin > [8-lysine]vasopressin; [lysine]-bradykinin and [4-proline]oxytocin were not inhibitory in the dose ranges tested. These results demonstrate that isolated mammary cells possess oxytocin receptors with properties comparable to those found in broken mammary cell preparations."}
{"id": "PMID:195967", "title": "The control of human WI-38 cell proliferation by extracellular calcium and its elimination by SV-40 virus-induced proliferative transformation.", "content": "The proliferative activity of diploid human WI-38 cells in sparse cultures depends on the extracellular concentration of free (or physiologically available) calcium, and cultivation in a medium having a calcium concentration of 0.1 mM or less gradually, but reversibly, arrest their proliferative development in the prereplicative (G1) phase of the cell cycle. Calcium's proliferative control of this cell type is eliminated by proliferative and morphological transformation by the oncogenic SV-40 virus, and the proliferative activity of SV-WI-38 cells in sparse cultures is unaffected by variation of the extracellular free calcium concentration between 0.00 and 1.25 mM.", "contents": "The control of human WI-38 cell proliferation by extracellular calcium and its elimination by SV-40 virus-induced proliferative transformation. The proliferative activity of diploid human WI-38 cells in sparse cultures depends on the extracellular concentration of free (or physiologically available) calcium, and cultivation in a medium having a calcium concentration of 0.1 mM or less gradually, but reversibly, arrest their proliferative development in the prereplicative (G1) phase of the cell cycle. Calcium's proliferative control of this cell type is eliminated by proliferative and morphological transformation by the oncogenic SV-40 virus, and the proliferative activity of SV-WI-38 cells in sparse cultures is unaffected by variation of the extracellular free calcium concentration between 0.00 and 1.25 mM."}
{"id": "PMID:195968", "title": "A cell membrane alteration specifically induced by SV40 transformation.", "content": "Transformation of mouse 3T3 cells by SV40 results in a specific membrane modification which renders cells resistant to the killing action of the lipophilic antibiotic Amphotericin B. This alteration is under genetic cellular control and is specific for SV40 transformation since transformation with polyoma or mouse sarcoma viruses does not confer resistance to the antibiotic. Analogous resistance is induced by SV40 transformation of primary human fibroblast cells. The acquired resistance is not due to decreased binding of Amphotericin B and is partially reversed if cells are grown in the presence of cholesterol. The results are interpreted as a specific change of sterol structure of the membrane or the loss of a minor cholesterol fraction responsible for the killing action of the antibiotic.", "contents": "A cell membrane alteration specifically induced by SV40 transformation. Transformation of mouse 3T3 cells by SV40 results in a specific membrane modification which renders cells resistant to the killing action of the lipophilic antibiotic Amphotericin B. This alteration is under genetic cellular control and is specific for SV40 transformation since transformation with polyoma or mouse sarcoma viruses does not confer resistance to the antibiotic. Analogous resistance is induced by SV40 transformation of primary human fibroblast cells. The acquired resistance is not due to decreased binding of Amphotericin B and is partially reversed if cells are grown in the presence of cholesterol. The results are interpreted as a specific change of sterol structure of the membrane or the loss of a minor cholesterol fraction responsible for the killing action of the antibiotic."}
{"id": "PMID:195971", "title": "High-performance liquid chromatographic analysis of dianhydrogalactitol in plasma by derivatization with sodium diethyldithiocarbamate.", "content": "A high-performance liquid chromatographic method is described for measuring submicrogram quantities of dianhydrogalactitol, a promising anti-neoplastic agent, in plasma. The drug is derivatized directly in plasma with sodium diethyldithiocarbamate to form a bis(dithiocarbamoyl) ester which absorbs UV light at 254 nm (am 17,000). The derivatized product is then extracted quantitatively into chloroform and separated by normal phase chromatography (muBondpak CN column). Dianhydrogalactitol concentration below 50 ng/ml of plasma can be detected in the eluent.", "contents": "High-performance liquid chromatographic analysis of dianhydrogalactitol in plasma by derivatization with sodium diethyldithiocarbamate. A high-performance liquid chromatographic method is described for measuring submicrogram quantities of dianhydrogalactitol, a promising anti-neoplastic agent, in plasma. The drug is derivatized directly in plasma with sodium diethyldithiocarbamate to form a bis(dithiocarbamoyl) ester which absorbs UV light at 254 nm (am 17,000). The derivatized product is then extracted quantitatively into chloroform and separated by normal phase chromatography (muBondpak CN column). Dianhydrogalactitol concentration below 50 ng/ml of plasma can be detected in the eluent."}
{"id": "PMID:195972", "title": "Vitamin D metabolism and the response to 1,25-dihydroxycholecalciferol in Osteoporosis.", "content": "The metabolism of isotopically-labelled cholecalciferol and the response to small doses of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was studied in a group of women with osteoporosis presenting with crush vertebral fracture. No abnormality of vitamin D metabolism was detected. The administration of 1 microgram 1,25-(OH)2D3 for between 8 and 20 days was associated with an increased intestinal absorption and urinary excretion of calcium but caused no improvement in calcium balance. There was a small but significant rise in serum calcium and phosphorus and significant reduction in immunoassayable parathyroid hormone levels during treatment. It is concluded that 1,25-(OH)2D3 is unlikely to be of value in the management of osteoporosis.", "contents": "Vitamin D metabolism and the response to 1,25-dihydroxycholecalciferol in Osteoporosis. The metabolism of isotopically-labelled cholecalciferol and the response to small doses of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was studied in a group of women with osteoporosis presenting with crush vertebral fracture. No abnormality of vitamin D metabolism was detected. The administration of 1 microgram 1,25-(OH)2D3 for between 8 and 20 days was associated with an increased intestinal absorption and urinary excretion of calcium but caused no improvement in calcium balance. There was a small but significant rise in serum calcium and phosphorus and significant reduction in immunoassayable parathyroid hormone levels during treatment. It is concluded that 1,25-(OH)2D3 is unlikely to be of value in the management of osteoporosis."}
{"id": "PMID:195973", "title": "Plasma testosterone profiles in Cushing's syndrome.", "content": "Elevated plasma testosterone levels were found in 8 women with Cushing's disease and oligo-or amenorrhea and/or hirsutism. In 4 men with Cushing's syndrome either due to adrenal hyperplasia or adenoma, plasma testosterone levels were lowered. Three of these 4 men complained of impotence or loss of libodo. Evidence for a major adrenal origin of the elevated testosterone values in the women with Cushing's disease was derived from the parallel suppression of cortisol and testosterone during dexamethasone administration, the testosterone responsiveness to ACTH and its dramatic fall after adrenalectomy. In the men with Cushing's syndrome the lowered plasma testosterone values were further suppressed by high doses of dexamethasone irrespective of concomitant cortisol suppression. Adrenalectomy or adenotomy restored the decreased plasma testosterone levels to normal. In women with Cushing's syndrome adrenal hyperandrogenism may account for the sexual and gonadal disturbances, in men glucocorticoid induced suppression of Leydig cell function may be responsible.", "contents": "Plasma testosterone profiles in Cushing's syndrome. Elevated plasma testosterone levels were found in 8 women with Cushing's disease and oligo-or amenorrhea and/or hirsutism. In 4 men with Cushing's syndrome either due to adrenal hyperplasia or adenoma, plasma testosterone levels were lowered. Three of these 4 men complained of impotence or loss of libodo. Evidence for a major adrenal origin of the elevated testosterone values in the women with Cushing's disease was derived from the parallel suppression of cortisol and testosterone during dexamethasone administration, the testosterone responsiveness to ACTH and its dramatic fall after adrenalectomy. In the men with Cushing's syndrome the lowered plasma testosterone values were further suppressed by high doses of dexamethasone irrespective of concomitant cortisol suppression. Adrenalectomy or adenotomy restored the decreased plasma testosterone levels to normal. In women with Cushing's syndrome adrenal hyperandrogenism may account for the sexual and gonadal disturbances, in men glucocorticoid induced suppression of Leydig cell function may be responsible."}
{"id": "PMID:195975", "title": "Comparison of antibody-dependent cellular cytotoxicity and complement-dependent antibody lysis of herpes simplex virus-infected cells as methods of detecting antiviral antibodies in human sera.", "content": "An antibody-dependent cellular cytotoxicity (ADCC) assay was used to detect antibodies to the herpes simplex viruses in humans sera. The assay utilized the release of 51Cr from BHK-21 cells infected with the viruses, hamster peritoneal exudate cells as effector cells, and antiviral antibodies in human sera. The technique was found to be far more sensitive than complement-dependent antibody lysis of infected cells and virus neutralization. The ADCC assay was useful in detecting antibodies in sera that had low titers or no antibodies detectable by other methods. In a sample of 100 sera from university students, 40 were positive by complement-dependent lysis whereas 73 were positive by ADCC. Of 400 sera from women with cervical cancer, 17 did not have detectable antibodies by microneutralization or complement-dependent lysis; however, all sera were positive by ADCC, suggesting that all of the women had been infected in the past with one or both types of herpes simplex virus.", "contents": "Comparison of antibody-dependent cellular cytotoxicity and complement-dependent antibody lysis of herpes simplex virus-infected cells as methods of detecting antiviral antibodies in human sera. An antibody-dependent cellular cytotoxicity (ADCC) assay was used to detect antibodies to the herpes simplex viruses in humans sera. The assay utilized the release of 51Cr from BHK-21 cells infected with the viruses, hamster peritoneal exudate cells as effector cells, and antiviral antibodies in human sera. The technique was found to be far more sensitive than complement-dependent antibody lysis of infected cells and virus neutralization. The ADCC assay was useful in detecting antibodies in sera that had low titers or no antibodies detectable by other methods. In a sample of 100 sera from university students, 40 were positive by complement-dependent lysis whereas 73 were positive by ADCC. Of 400 sera from women with cervical cancer, 17 did not have detectable antibodies by microneutralization or complement-dependent lysis; however, all sera were positive by ADCC, suggesting that all of the women had been infected in the past with one or both types of herpes simplex virus."}
{"id": "PMID:195976", "title": "Quantitation of antibody to non-hemagglutinating viruses by single radial hemolysis: serological test for human coronaviruses.", "content": "A single radial hemolysis test was developed for quantitation of specific antibody to non-hemagglutinating viruses. With the human coronaviruses as models, this test utilizes the binding properties of the chromic cation to attach viruses to glutaraldehyde-treated sheep erythrocytes. The most satisfactory system consisted of stabilizing washed sheep erythrocytes with 0.0073% glutaraldehyde for 15 min at 23 degrees C, binding a high concentration of virus to a 25% erythrocyte suspension with 0.0016% chromic chloride for 20 min at 23 degrees C, stopping the reaction with phosphate-saline, and finally mixing the treated, rewashed cells with complement and agarose at 45 degrees C to prepare a slide gel. The gel mix, which was dispensed in plastic plates (23 by 73 mm) in 3-ml volumes, consisted of 1% agarose, 0.1% sodium azide, 5% reconstituted complement, and 0.82% treated cells. Wells 2 mm in diameter were loaded with 5 mul of antiserum, incubated for 18 h at 4 degrees C for diffusion of antiserum and fixation of complement, and then incubated for 8 to 24 h at 37 degrees C for development of hemolysis zones. The diameter of a zone was linearly related to antibody concentration, as determined by conventional serological tests. This single radial hemolysis test was applicable to human and animal coronaviruses and to selected serotypes of the adenovirus, picornavirus, rhabdovirus, and rotavirus groups.", "contents": "Quantitation of antibody to non-hemagglutinating viruses by single radial hemolysis: serological test for human coronaviruses. A single radial hemolysis test was developed for quantitation of specific antibody to non-hemagglutinating viruses. With the human coronaviruses as models, this test utilizes the binding properties of the chromic cation to attach viruses to glutaraldehyde-treated sheep erythrocytes. The most satisfactory system consisted of stabilizing washed sheep erythrocytes with 0.0073% glutaraldehyde for 15 min at 23 degrees C, binding a high concentration of virus to a 25% erythrocyte suspension with 0.0016% chromic chloride for 20 min at 23 degrees C, stopping the reaction with phosphate-saline, and finally mixing the treated, rewashed cells with complement and agarose at 45 degrees C to prepare a slide gel. The gel mix, which was dispensed in plastic plates (23 by 73 mm) in 3-ml volumes, consisted of 1% agarose, 0.1% sodium azide, 5% reconstituted complement, and 0.82% treated cells. Wells 2 mm in diameter were loaded with 5 mul of antiserum, incubated for 18 h at 4 degrees C for diffusion of antiserum and fixation of complement, and then incubated for 8 to 24 h at 37 degrees C for development of hemolysis zones. The diameter of a zone was linearly related to antibody concentration, as determined by conventional serological tests. This single radial hemolysis test was applicable to human and animal coronaviruses and to selected serotypes of the adenovirus, picornavirus, rhabdovirus, and rotavirus groups."}
{"id": "PMID:195977", "title": "Solid-phase enzyme immunoassay for immunoglobulin M antibodies to cytomegalovirus.", "content": "A sensitive, solid-phase enzyme immunoassay for the detection of immunoglobulin M antibodies to cytomegalovirus is described. The results of the enzyme immunoassay correlated well with those obtained by an indirect immunofluorescence method. Horseradish peroxidase proved to be a more sensitive label than alkaline phosphatase. Nonspecific reactions, occurring with commercially available cytomegalovirus antigens, could be avoided by using a nuclear antigen prepared from sonically disrupted nuclei of cytomegalovirus-infected cells.", "contents": "Solid-phase enzyme immunoassay for immunoglobulin M antibodies to cytomegalovirus. A sensitive, solid-phase enzyme immunoassay for the detection of immunoglobulin M antibodies to cytomegalovirus is described. The results of the enzyme immunoassay correlated well with those obtained by an indirect immunofluorescence method. Horseradish peroxidase proved to be a more sensitive label than alkaline phosphatase. Nonspecific reactions, occurring with commercially available cytomegalovirus antigens, could be avoided by using a nuclear antigen prepared from sonically disrupted nuclei of cytomegalovirus-infected cells."}
{"id": "PMID:195978", "title": "Gelatin neutralization of the inhibitory effect of sodium polyanethol sulfonate on Neisseria meningitidis in blood culture media.", "content": "The inhibitory effect of sodium polyanethol sulfonate (0.05%) upon growth of Neisseria meningitidis was found to be neutralized by adding gelatin (l.1%) to the growth medium. The neutralizing effect was demonstrated in solid medium, as well as in nutrient broth for blood cultures. The findings parallel those of Wilkins and West (6) regarding gelatin neutralization of the inhibitory effect of sodium polyanethol sulfonate on Peptostreptococcus anaerobius.", "contents": "Gelatin neutralization of the inhibitory effect of sodium polyanethol sulfonate on Neisseria meningitidis in blood culture media. The inhibitory effect of sodium polyanethol sulfonate (0.05%) upon growth of Neisseria meningitidis was found to be neutralized by adding gelatin (l.1%) to the growth medium. The neutralizing effect was demonstrated in solid medium, as well as in nutrient broth for blood cultures. The findings parallel those of Wilkins and West (6) regarding gelatin neutralization of the inhibitory effect of sodium polyanethol sulfonate on Peptostreptococcus anaerobius."}
{"id": "PMID:195979", "title": "Maintenance of viability and comparison of identification methods for influenza and other respiratory viruses of humans.", "content": "A comparison of Hanks balanced salt solution, veal infusion broth (VIB), and charcoal viral transport medium for maintaining viability of type A influenza virus indicated approximately equal survival of virus on all three media at -70 and 4 degrees C, whereas at 25 degrees C virus survived best in VIB. VIB supplemented with bovine serum albumin was used as transport medium in a community-wide surveillance of febrile respiratory disease for influenza viruses. Unfrozen throat swab specimens were placed in VIB and stored at 4 degrees C for up to 5 days without effect on isolation frequencies of either type A or type B influenza virus or type 1 or type 3 parainfluenza virus. Comparison of indirect immunofluorescence with hemadsorption for detection of type A influenza virus in rhesus monkey kidney cultures revealed a requirement for at least five fluorescing cells to eliminate false positive indirect immunofluorescence tests and at least 3 days of incubation to eliminate false negative tests when compared with hemadsorption at later times. Detection frequencies for the two methods after 2 and 3 days of incubation were not significantly different.", "contents": "Maintenance of viability and comparison of identification methods for influenza and other respiratory viruses of humans. A comparison of Hanks balanced salt solution, veal infusion broth (VIB), and charcoal viral transport medium for maintaining viability of type A influenza virus indicated approximately equal survival of virus on all three media at -70 and 4 degrees C, whereas at 25 degrees C virus survived best in VIB. VIB supplemented with bovine serum albumin was used as transport medium in a community-wide surveillance of febrile respiratory disease for influenza viruses. Unfrozen throat swab specimens were placed in VIB and stored at 4 degrees C for up to 5 days without effect on isolation frequencies of either type A or type B influenza virus or type 1 or type 3 parainfluenza virus. Comparison of indirect immunofluorescence with hemadsorption for detection of type A influenza virus in rhesus monkey kidney cultures revealed a requirement for at least five fluorescing cells to eliminate false positive indirect immunofluorescence tests and at least 3 days of incubation to eliminate false negative tests when compared with hemadsorption at later times. Detection frequencies for the two methods after 2 and 3 days of incubation were not significantly different."}
{"id": "PMID:195980", "title": "Preparation and evaluation of a noninfectious monkey pox virus vaccine.", "content": "Monkey pox virus was mechanically disrupted by low temperature and high pressure into soluble and insoluble fractions. Soluble fractions elicited virus-neutralizing antibodies (1:20 to 1:160) in rabbits, whereas the insoluble (in saline) fractions did not (less than 1:5). No infectious virus was detected after the disruption procedure. Rhesus monkeys immunized with the soluble fraction elicited virus-neutralizing (1:1,200), complement-fixing (1:16), and hemagglutinating-inhibiting (1:80 to 1:160) antibody titers and were completely protected against monkey pox virus-induced disease. This model of monkey pox virus subunit vaccine preparation may prove to be useful in developing an efficacious noninfectious vaccinia vaccine for use in high-risk individuals.", "contents": "Preparation and evaluation of a noninfectious monkey pox virus vaccine. Monkey pox virus was mechanically disrupted by low temperature and high pressure into soluble and insoluble fractions. Soluble fractions elicited virus-neutralizing antibodies (1:20 to 1:160) in rabbits, whereas the insoluble (in saline) fractions did not (less than 1:5). No infectious virus was detected after the disruption procedure. Rhesus monkeys immunized with the soluble fraction elicited virus-neutralizing (1:1,200), complement-fixing (1:16), and hemagglutinating-inhibiting (1:80 to 1:160) antibody titers and were completely protected against monkey pox virus-induced disease. This model of monkey pox virus subunit vaccine preparation may prove to be useful in developing an efficacious noninfectious vaccinia vaccine for use in high-risk individuals."}
{"id": "PMID:195981", "title": "Epstein-Barr virus viral capsid antigen titer by immunofluorescence with microplates: new semiautomated method based on the microtiter system.", "content": "A semiautomated method of an indirect immunofluorescence technique for the titration of antibodies directed against viral capsid antigens of Epstein-Barr virus has been developed with Microtiter system units. By this method, a technician is able to titrate some hundred samples daily. The technique is safe, easy, and reproducible. The various procedures are described, and the sensitivity of the test is discussed.", "contents": "Epstein-Barr virus viral capsid antigen titer by immunofluorescence with microplates: new semiautomated method based on the microtiter system. A semiautomated method of an indirect immunofluorescence technique for the titration of antibodies directed against viral capsid antigens of Epstein-Barr virus has been developed with Microtiter system units. By this method, a technician is able to titrate some hundred samples daily. The technique is safe, easy, and reproducible. The various procedures are described, and the sensitivity of the test is discussed."}
{"id": "PMID:195982", "title": "Solid-phase radioimmunoassay for detecting bovine (neonatal calf diarrhea) rotavirus antibody.", "content": "An indirect solid-phase microradioimmunoassay is described for detecting antibodies against rotaviruses. The test involved ethanol fixation of microcultures of bovine rotavirus-infected BSC-1 cells and reacetion with bovine antirotavirus serum, followed by 125I-labeled rabbit anti-bovine immunoglobulin G. The technique was shown to be virus specific and highly sensitive. The fixed microcultures could be stored at 4 degrees C for at least 2 months without affecting the sensitivity of the test. The application of this system for the detection of rotavirus antibodies in humans is briefly discussed.", "contents": "Solid-phase radioimmunoassay for detecting bovine (neonatal calf diarrhea) rotavirus antibody. An indirect solid-phase microradioimmunoassay is described for detecting antibodies against rotaviruses. The test involved ethanol fixation of microcultures of bovine rotavirus-infected BSC-1 cells and reacetion with bovine antirotavirus serum, followed by 125I-labeled rabbit anti-bovine immunoglobulin G. The technique was shown to be virus specific and highly sensitive. The fixed microcultures could be stored at 4 degrees C for at least 2 months without affecting the sensitivity of the test. The application of this system for the detection of rotavirus antibodies in humans is briefly discussed."}
{"id": "PMID:195983", "title": "Metabolic effects of diphosphonate in primary hyperparathyroidism.", "content": "Six patients with primary hyperparathyroidism (PHPT) and one with squamous cell carcinoma of the esophagus with parathyroid hormone excess received disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at a daily dose of 20 mg/kg orally. During treatment, the decrease in urinary calcium, total urinary hydroxyproline, and fasting urinary calcium suggested an inhibition of bone resorption. Serum calcium intestinal absorption of calcium and urinary cyclic adenosine monophosphate (cAMP) did not change significantly. This preliminary study indicates a possible role of diphosphonates in the management of inoperable cases of primary hyperparathyroidism or pseudohyperparathyroidism.", "contents": "Metabolic effects of diphosphonate in primary hyperparathyroidism. Six patients with primary hyperparathyroidism (PHPT) and one with squamous cell carcinoma of the esophagus with parathyroid hormone excess received disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at a daily dose of 20 mg/kg orally. During treatment, the decrease in urinary calcium, total urinary hydroxyproline, and fasting urinary calcium suggested an inhibition of bone resorption. Serum calcium intestinal absorption of calcium and urinary cyclic adenosine monophosphate (cAMP) did not change significantly. This preliminary study indicates a possible role of diphosphonates in the management of inoperable cases of primary hyperparathyroidism or pseudohyperparathyroidism."}
{"id": "PMID:195984", "title": "Effects of parathyroid hormone on cyclic AMP, cyclic GMP, and efflux of calcium in isolated renal tubules.", "content": "The effects of parathyroid hormone (PTH) on concentrations of cyclic AMP and cyclic GMP were investigated in isolated renal cortical tubules from hamsters. Efflux of 45Ca from tubules was compared to temporal changes in both cyclic nucleotide concentrations. A rapid increase in cyclic AMP occurred following addition of PTH which was maximal by 1 min but decreased over the next 4 min period. Cyclic GMP concentrations were not significantly altered at 1 min but increased between 1 and 5 min from basal levels. Concentrations of both nucleotides remained significantly elevated from basal levels between 5 and 15 min following PTH. Efflux of 45Ca was increased by PTH with time-course changes closely paralleling changes in cyclic GMP concentrations. Changes in both cyclic AMP and cyclic GMP were related to PTH concentrations of the incubation media and were increased by addition of theophylline. Increasing the calcium concentration from 1 to 3 mM did not significantly alter the effect of PTH on cyclic AMP, however, cyclic GMP concentrations were further increased.", "contents": "Effects of parathyroid hormone on cyclic AMP, cyclic GMP, and efflux of calcium in isolated renal tubules. The effects of parathyroid hormone (PTH) on concentrations of cyclic AMP and cyclic GMP were investigated in isolated renal cortical tubules from hamsters. Efflux of 45Ca from tubules was compared to temporal changes in both cyclic nucleotide concentrations. A rapid increase in cyclic AMP occurred following addition of PTH which was maximal by 1 min but decreased over the next 4 min period. Cyclic GMP concentrations were not significantly altered at 1 min but increased between 1 and 5 min from basal levels. Concentrations of both nucleotides remained significantly elevated from basal levels between 5 and 15 min following PTH. Efflux of 45Ca was increased by PTH with time-course changes closely paralleling changes in cyclic GMP concentrations. Changes in both cyclic AMP and cyclic GMP were related to PTH concentrations of the incubation media and were increased by addition of theophylline. Increasing the calcium concentration from 1 to 3 mM did not significantly alter the effect of PTH on cyclic AMP, however, cyclic GMP concentrations were further increased."}
{"id": "PMID:195985", "title": "Characterization of a spectrophotometric assay for cAMP phosphodiesterase.", "content": "The hydrolysis of cAMP can be monitored spectrophotometrically through the conversion of 5' AMP to 5' IMP using a specific 5' AMP amino-hydrolase (EC3.5.4.6). The optical properties and extinction coefficient differences of these compounds have been quantitatively determined. Phosphodiesterase assayed in this manner is linear with respect to time and enzyme concentration, and is more reliable than conventional assay procedures. Due to the high specificity of the assay system phosphodiesterase can be selectively assayed in unfractionated cytosol. The assay, when conducted on a conventional spectrophotometer, can detect the hydrolysis of 0.5 nmoles cAMP per min.", "contents": "Characterization of a spectrophotometric assay for cAMP phosphodiesterase. The hydrolysis of cAMP can be monitored spectrophotometrically through the conversion of 5' AMP to 5' IMP using a specific 5' AMP amino-hydrolase (EC3.5.4.6). The optical properties and extinction coefficient differences of these compounds have been quantitatively determined. Phosphodiesterase assayed in this manner is linear with respect to time and enzyme concentration, and is more reliable than conventional assay procedures. Due to the high specificity of the assay system phosphodiesterase can be selectively assayed in unfractionated cytosol. The assay, when conducted on a conventional spectrophotometer, can detect the hydrolysis of 0.5 nmoles cAMP per min."}
{"id": "PMID:195987", "title": "Evidence for differences in protein kinase modulator and and phosphodiesterase activator.", "content": "Both protein kinase modulator and phosphodiesterase activator activities were present in the supernatant fluid of a homogenate of bovine brain. These were separated on a DEAE-cellulose column chromatography. Separation was also achieved by an isoelectrofocusing fractionation of the supernatant fluid, isoelectric points of proteins kinase modulator and phospodiesterase activator being 4.25 and 4.44, respectively. Phospodiesterase activator was purified from bovine brain to an apparent homogenity by a procedure which did not involve a drastic treatment such as boiling. The purification of phosphodiesterase activator resulted in removing the protein kinase modulator activity and the ratio of the activity of protein kinase modulator to that of phosphodiesterase activator in the sample decreased as the purification proceeded.", "contents": "Evidence for differences in protein kinase modulator and and phosphodiesterase activator. Both protein kinase modulator and phosphodiesterase activator activities were present in the supernatant fluid of a homogenate of bovine brain. These were separated on a DEAE-cellulose column chromatography. Separation was also achieved by an isoelectrofocusing fractionation of the supernatant fluid, isoelectric points of proteins kinase modulator and phospodiesterase activator being 4.25 and 4.44, respectively. Phospodiesterase activator was purified from bovine brain to an apparent homogenity by a procedure which did not involve a drastic treatment such as boiling. The purification of phosphodiesterase activator resulted in removing the protein kinase modulator activity and the ratio of the activity of protein kinase modulator to that of phosphodiesterase activator in the sample decreased as the purification proceeded."}
{"id": "PMID:195988", "title": "H2-histaminergic activity of clonidine in the guinea pig heart.", "content": "Clonidine perfusion (1 muM) or injection (9.4 to 150.4 nmoles) into the isolated perfused guinea pig heart caused an increase in contractile force, phosphorylase a and cyclic adenosine monophosphate (cyclic AMP)  levels. The effects of clonidine were blocked by burimamide (30 muM). Proranolol (1 muM), phentolamine (1 muM) or reserpine treatment (5 mg/kg i.p., 24 hours prior to the experiment) did not influence the cardiac effects of clonidine. Clonidine (0.1 - 100 muM) also produced a dose dependent positive inotropic effect on right ventricle strips but had a negative chronotropic effect on the spontaneously beating right atria at higher concentration (0.1 to 1.0 M). Burimamide did not block the clonidine-induced negative chronotropic effect. Clonidine did not increase contractile force in guinea pig left atria. It also did not influence the isoproterenol-and phenylephrine-induced increases in cardiac force of contraction but did antagonize the positive inotropic effect of 4-methylhistamine in the right ventricle. This observation suggests that clonidine may compete with 4-methylhistamine for the same receptor sites. The results indicate that the cardiac receptors for both biochemical and mechanical effects of clonidine are histamine receptors of the H2-type.", "contents": "H2-histaminergic activity of clonidine in the guinea pig heart. Clonidine perfusion (1 muM) or injection (9.4 to 150.4 nmoles) into the isolated perfused guinea pig heart caused an increase in contractile force, phosphorylase a and cyclic adenosine monophosphate (cyclic AMP)  levels. The effects of clonidine were blocked by burimamide (30 muM). Proranolol (1 muM), phentolamine (1 muM) or reserpine treatment (5 mg/kg i.p., 24 hours prior to the experiment) did not influence the cardiac effects of clonidine. Clonidine (0.1 - 100 muM) also produced a dose dependent positive inotropic effect on right ventricle strips but had a negative chronotropic effect on the spontaneously beating right atria at higher concentration (0.1 to 1.0 M). Burimamide did not block the clonidine-induced negative chronotropic effect. Clonidine did not increase contractile force in guinea pig left atria. It also did not influence the isoproterenol-and phenylephrine-induced increases in cardiac force of contraction but did antagonize the positive inotropic effect of 4-methylhistamine in the right ventricle. This observation suggests that clonidine may compete with 4-methylhistamine for the same receptor sites. The results indicate that the cardiac receptors for both biochemical and mechanical effects of clonidine are histamine receptors of the H2-type."}
{"id": "PMID:196001", "title": "Impaired monosynaptic potentiation in in vitro hippocampal slices from aged, memory-deficient rats.", "content": "Neurophysiological experiments were conducted in vitro on 400 mu thick transverse hippocampal slices from aged and young rats. These slices exhibit neurophysiological responses similar to those of intact hippocampus. The aged rats have previously been found to exhibit impaired retention. Synaptic responses of the Schaffer collateral system were not found to be different between aged and young slices when elicited by very low frequency (0.3 Hz) electrical stimulation. However, the aged slices exhibited marked deficits in frequency and posttetanic potentiation in response to repetitive stimulation (15 Hz). This deficit was interpreted as resulting from an increased tendency to synaptic depression, rather than from impaired potentiation processes. The possibility of a relationship of these physiological deficits in hippocampal synaptic plasticity to the deficits in behavioral plasticity found in these aged animals is considered.", "contents": "Impaired monosynaptic potentiation in in vitro hippocampal slices from aged, memory-deficient rats. Neurophysiological experiments were conducted in vitro on 400 mu thick transverse hippocampal slices from aged and young rats. These slices exhibit neurophysiological responses similar to those of intact hippocampus. The aged rats have previously been found to exhibit impaired retention. Synaptic responses of the Schaffer collateral system were not found to be different between aged and young slices when elicited by very low frequency (0.3 Hz) electrical stimulation. However, the aged slices exhibited marked deficits in frequency and posttetanic potentiation in response to repetitive stimulation (15 Hz). This deficit was interpreted as resulting from an increased tendency to synaptic depression, rather than from impaired potentiation processes. The possibility of a relationship of these physiological deficits in hippocampal synaptic plasticity to the deficits in behavioral plasticity found in these aged animals is considered."}
{"id": "PMID:196002", "title": "[Chemotherapy in placental tumors].", "content": "Chemotherapy is a useful element, but not the only element, for controlling placental tumours. In cases of simple mole routine chemotherapy does not seem to be justified and usually, in 9 cases out of 10, it is useless. It is certainly not always effective and sometimes it may even be dangerous because of the development of chemoresistance. Invasive mole and tumours where a histological diagnosis has not been made and where there is no particularly unfavourable prognosis, usually heal with twice weekly methotrexate carried on for two months after cure has been confirmed clinically, radiologically and biologically. Choriocarcinomata and cases where histology has not been carried out but which have poor prognosis (extra-pulmonary metastases, numerous or large pulmonary metastases, long delay in treatment and the excretion of high levels of HCG) justify chemotherapy in which vincristine is followed by methotrexate or vincristine is followed by actinomycine D. For cure in these bad cases secondary surgery to remove residual lesions, either in the uterus or the lungs, may be necessary.", "contents": "[Chemotherapy in placental tumors]. Chemotherapy is a useful element, but not the only element, for controlling placental tumours. In cases of simple mole routine chemotherapy does not seem to be justified and usually, in 9 cases out of 10, it is useless. It is certainly not always effective and sometimes it may even be dangerous because of the development of chemoresistance. Invasive mole and tumours where a histological diagnosis has not been made and where there is no particularly unfavourable prognosis, usually heal with twice weekly methotrexate carried on for two months after cure has been confirmed clinically, radiologically and biologically. Choriocarcinomata and cases where histology has not been carried out but which have poor prognosis (extra-pulmonary metastases, numerous or large pulmonary metastases, long delay in treatment and the excretion of high levels of HCG) justify chemotherapy in which vincristine is followed by methotrexate or vincristine is followed by actinomycine D. For cure in these bad cases secondary surgery to remove residual lesions, either in the uterus or the lungs, may be necessary."}
{"id": "PMID:196024", "title": "Enhancement of the PGE1 response of macrophages by concanavalin A and colchicine.", "content": "The effect of concanavalin A (Con A) and colchicine on the prostaglandin E1 (PGE1)-mediated cyclic AMP generation in rat peritoneal macrophages have been studied. Although Con A and colchicine by themselves did not affect cyclic AMP levels, they greatly enhanced cyclic AMP production induced by PGE1. There was not only augmentation of cyclic AMP levels at maximally active concentrations of PGE1, but also an increased sensitivity to low (inactive) concentrations of PGE1. Except for lentil lectin, none of the other lectins affected PGE1 sensitivity whereas lumicolchicine was as effective as colchicine. In addition, both Con A and colchicine raised the sensitivity to isoproterenol and choleraenterotoxin. Although details of the mechanisms by which Con A or colchicine influenced the membrane-bound adenyl cyclase and PGE1 receptors remain unclear, these observations suggest that certain alterations of the cell membrane may render macrophages more susceptible to the regulating effects of prostaglandins.", "contents": "Enhancement of the PGE1 response of macrophages by concanavalin A and colchicine. The effect of concanavalin A (Con A) and colchicine on the prostaglandin E1 (PGE1)-mediated cyclic AMP generation in rat peritoneal macrophages have been studied. Although Con A and colchicine by themselves did not affect cyclic AMP levels, they greatly enhanced cyclic AMP production induced by PGE1. There was not only augmentation of cyclic AMP levels at maximally active concentrations of PGE1, but also an increased sensitivity to low (inactive) concentrations of PGE1. Except for lentil lectin, none of the other lectins affected PGE1 sensitivity whereas lumicolchicine was as effective as colchicine. In addition, both Con A and colchicine raised the sensitivity to isoproterenol and choleraenterotoxin. Although details of the mechanisms by which Con A or colchicine influenced the membrane-bound adenyl cyclase and PGE1 receptors remain unclear, these observations suggest that certain alterations of the cell membrane may render macrophages more susceptible to the regulating effects of prostaglandins."}
{"id": "PMID:196027", "title": "Epidermal adenylate cyclase systems: the retention of hormone responsiveness after enzymatic separation of pure epidermis.", "content": "Although it has been shown that keratome-sliced skin contains active adenylate cyclase systems which respond to various hormones and drugs, unequivocal proof that the epidermis contains these hormone-responsive systems is still lacking. We demonstrate in this study that \"pure\" epidermis obtained after either collagenase or trypsin treatment does contain the hormone-sensitive adenylate cyclase systems.", "contents": "Epidermal adenylate cyclase systems: the retention of hormone responsiveness after enzymatic separation of pure epidermis. Although it has been shown that keratome-sliced skin contains active adenylate cyclase systems which respond to various hormones and drugs, unequivocal proof that the epidermis contains these hormone-responsive systems is still lacking. We demonstrate in this study that \"pure\" epidermis obtained after either collagenase or trypsin treatment does contain the hormone-sensitive adenylate cyclase systems."}
{"id": "PMID:196029", "title": "Infection of the central nervous system produced by mixtures of defective-interfering particles and wild-type vesicular stomatitis virus in mice.", "content": "In contrast to wild-type vesicular stomatitis virus (VSV), which produces a fulminant illness with death in two to three days, mixtures of homologous defective autointerfering (DI) particles and wild-type VSV (DI-wild-type VSV) injected intracerebrally into mice resulted in a slowly progressive disease of the central nervous system (CNS). In fact, mice inoculated with DI-wild-type VSV survived up to nine days after infection and displayed striking paralysis of the hind limbs. The slowly progressive CNS disease accompanying infection with DI-wild-type VSV was characterized by production of only 1% of the amount of VSV recovered when wild-type VSV was injected alone. Morphologically, mice infected with DI-wild-type VSV displayed a spectrum of pathologic changes not encountered with disease due to wild-type VSV alone. These changes included the presence of parenchymal necrosis in the spinal cord, changes in and secondary demyelination of the white matter, striking leptomeningeal inflammation, and spongiform changes in the gray matter of the neuropil. Since these pathological features are not found when CNS disease results from either wild-type VSV or temperature-sensitive (ts) mutants of VSV, it is suggested that CNS infection with ts VSV is not mediated principally by production of DI particles. Furthermore, in vivo CNS infection with DI-wild-type VSV did not appear to be mediated by production of ts VSV mutants.", "contents": "Infection of the central nervous system produced by mixtures of defective-interfering particles and wild-type vesicular stomatitis virus in mice. In contrast to wild-type vesicular stomatitis virus (VSV), which produces a fulminant illness with death in two to three days, mixtures of homologous defective autointerfering (DI) particles and wild-type VSV (DI-wild-type VSV) injected intracerebrally into mice resulted in a slowly progressive disease of the central nervous system (CNS). In fact, mice inoculated with DI-wild-type VSV survived up to nine days after infection and displayed striking paralysis of the hind limbs. The slowly progressive CNS disease accompanying infection with DI-wild-type VSV was characterized by production of only 1% of the amount of VSV recovered when wild-type VSV was injected alone. Morphologically, mice infected with DI-wild-type VSV displayed a spectrum of pathologic changes not encountered with disease due to wild-type VSV alone. These changes included the presence of parenchymal necrosis in the spinal cord, changes in and secondary demyelination of the white matter, striking leptomeningeal inflammation, and spongiform changes in the gray matter of the neuropil. Since these pathological features are not found when CNS disease results from either wild-type VSV or temperature-sensitive (ts) mutants of VSV, it is suggested that CNS infection with ts VSV is not mediated principally by production of DI particles. Furthermore, in vivo CNS infection with DI-wild-type VSV did not appear to be mediated by production of ts VSV mutants."}
{"id": "PMID:196031", "title": "In vivo investigation of antibacterial ointments.", "content": "The clinically used topical antibiotic ointments, gentamicin 0.1%, oxytetracycline 3% w/polymyxin 0.1% and chloramphenicol 2% and an experimental preparation, 10-undecen-1-yl thiopseudourea iodide (AHR-1911) were studied for anti-infective action applied externally on the skin of mice inoculated subcutaneously with S. aureus and E. coli. In both infections statistically significant difference was encountered between curative and \"clinical\" healing rate in the case of the less effective preparations and/or dosages. The method appears suitable to establish and to compare the in vivo activity of ointments. This is not directly related to that of the aqueous drug solutions. AHR-1911, a powerful inhibitor of nucleic acid and protein synthesis, showed a bimodal action, with maximal effectiveness at 0.12-0.25% concentration, due presumably to the anti-inflammatory effect of higher concentrations. Direct evidence for the absorption of the drug from the application site was obtained using 14C labeled AHR-1911.", "contents": "In vivo investigation of antibacterial ointments. The clinically used topical antibiotic ointments, gentamicin 0.1%, oxytetracycline 3% w/polymyxin 0.1% and chloramphenicol 2% and an experimental preparation, 10-undecen-1-yl thiopseudourea iodide (AHR-1911) were studied for anti-infective action applied externally on the skin of mice inoculated subcutaneously with S. aureus and E. coli. In both infections statistically significant difference was encountered between curative and \"clinical\" healing rate in the case of the less effective preparations and/or dosages. The method appears suitable to establish and to compare the in vivo activity of ointments. This is not directly related to that of the aqueous drug solutions. AHR-1911, a powerful inhibitor of nucleic acid and protein synthesis, showed a bimodal action, with maximal effectiveness at 0.12-0.25% concentration, due presumably to the anti-inflammatory effect of higher concentrations. Direct evidence for the absorption of the drug from the application site was obtained using 14C labeled AHR-1911."}
{"id": "PMID:196033", "title": "Inhibition of maturation and metabolism in rat oocytes by cyclic amp.", "content": "It is known that dibutyryl cyclic AMP (dbcAMP) and theophylline inhibit the spontaneous maturation of isolated mouse oocytes. The present study demonstrates that dbcAMP (0.01-1.0 mM) as well as cyclic AMP (cAMP, 10 mM) and a phosphodiesterase inhibitor (IBMX, 0.01-1.0 mM) prevent spontaneous maturation of isolated rat oocytes. As reported earlier an increase in oxygen consumption by the oocyte was found following maturation. When the oocytes were cultured in the presence of dbcAMP or cAMP no change in respiration occurred during culture. These results argue against the theory that cAMP acts as a direct mediator of the action of luteinizing hormone (LH) on oocyte maturation. Furthermore they suggest that changes in oocyte energy metabolism are closely related to the maturation process.", "contents": "Inhibition of maturation and metabolism in rat oocytes by cyclic amp. It is known that dibutyryl cyclic AMP (dbcAMP) and theophylline inhibit the spontaneous maturation of isolated mouse oocytes. The present study demonstrates that dbcAMP (0.01-1.0 mM) as well as cyclic AMP (cAMP, 10 mM) and a phosphodiesterase inhibitor (IBMX, 0.01-1.0 mM) prevent spontaneous maturation of isolated rat oocytes. As reported earlier an increase in oxygen consumption by the oocyte was found following maturation. When the oocytes were cultured in the presence of dbcAMP or cAMP no change in respiration occurred during culture. These results argue against the theory that cAMP acts as a direct mediator of the action of luteinizing hormone (LH) on oocyte maturation. Furthermore they suggest that changes in oocyte energy metabolism are closely related to the maturation process."}
{"id": "PMID:196035", "title": "An extended genetic recombination map for foot-and-mouth diseases virus.", "content": "The original foot-and-mouth diseases virus recombination map (Lake, Priston & Slade, 1975), which include 35 mutagen-induced ts mutants, has been extended both in detail and size by the mapping of a further 33 ts mutants (9 mutagen-induced and 24 spontaneous). The size increase from 0.57% to 3.27% maximum recombination fequency was principally due to the use of a new standardization technique for recombination fequencies but, in addition, the original map distance was increased by approx. 30% due to the mapping of new mutations. As in the original map, there was a marked concentration of mutations near the guanidine (gs) locus, i.e. 83% of the mutants had mutations in the third of the map adjacent to the gs locus.", "contents": "An extended genetic recombination map for foot-and-mouth diseases virus. The original foot-and-mouth diseases virus recombination map (Lake, Priston & Slade, 1975), which include 35 mutagen-induced ts mutants, has been extended both in detail and size by the mapping of a further 33 ts mutants (9 mutagen-induced and 24 spontaneous). The size increase from 0.57% to 3.27% maximum recombination fequency was principally due to the use of a new standardization technique for recombination fequencies but, in addition, the original map distance was increased by approx. 30% due to the mapping of new mutations. As in the original map, there was a marked concentration of mutations near the guanidine (gs) locus, i.e. 83% of the mutants had mutations in the third of the map adjacent to the gs locus."}
{"id": "PMID:196036", "title": "Simian virus 40-Chinese hamster kidney cell interaction. III. Characteristics of chemical induction in a clone of virogenic transformed cells.", "content": "A number of chemical and physical agents were screened to determine their effectiveness in inducing simian virus (SV40) production in a virogenic clone of SV40-transformed Chinese hamster cells. Mitomycin C (MC) was the most effective inducing agent, and MC induction was further characterized. It was found that levels of infectious SV40 DNA were increased above control levels as early as 6 h after addition of MC to the culture medium and reached maximum levels by 48 h. Virus capsid (V) antigen and virions followed with a lag of about 24 h. V antigen production was sensitive to hydroxyurea, suggesting a dependence on virus DNA synthesis. The proportion of virus-producing cells (infectious centres) and the virus burst per cell were both stimulated by MC. Studies of 3H-thmidine incorporation demonstrated that the rate of SV40 DNA synthesis was maximal at 48 h post-induction, at which time cellular DNA synthesis was almost abolished. Caffeine, at doses not toxic to non-induced cells, strongly inhibited SV40production in both non-induced and induced cells, suggesting some role for DNA repair mechanisms.", "contents": "Simian virus 40-Chinese hamster kidney cell interaction. III. Characteristics of chemical induction in a clone of virogenic transformed cells. A number of chemical and physical agents were screened to determine their effectiveness in inducing simian virus (SV40) production in a virogenic clone of SV40-transformed Chinese hamster cells. Mitomycin C (MC) was the most effective inducing agent, and MC induction was further characterized. It was found that levels of infectious SV40 DNA were increased above control levels as early as 6 h after addition of MC to the culture medium and reached maximum levels by 48 h. Virus capsid (V) antigen and virions followed with a lag of about 24 h. V antigen production was sensitive to hydroxyurea, suggesting a dependence on virus DNA synthesis. The proportion of virus-producing cells (infectious centres) and the virus burst per cell were both stimulated by MC. Studies of 3H-thmidine incorporation demonstrated that the rate of SV40 DNA synthesis was maximal at 48 h post-induction, at which time cellular DNA synthesis was almost abolished. Caffeine, at doses not toxic to non-induced cells, strongly inhibited SV40production in both non-induced and induced cells, suggesting some role for DNA repair mechanisms."}
{"id": "PMID:196037", "title": "Quantification of the herpes simplex virus DNA present in biochemically transformed mouse cells and their revertants.", "content": "Four cell lines biochemically transformed by u.v.-irradiated herpes simplex virus contain virus DNA fragments ranging from 3 to 22% of the HSV genome. Of five revertant clones selected for 3H-TdR or BrdUrd resistance, four had lost all detectable virus DNA while the fifth, selected for BrdUrd resistance, retained the entire virus fragment but there was a reduction of virus copies per cell from 5 to 1. Three 'supertransformed' revertant cell lines contained virus DNA fragments ranging from 12 to 28%. The number of virus DNA fragments per cell ranged from 1 to 5 and clearly indicated that a single copy of the virus thymidine kinase gene is adequate for biochemical transformation. The determination of the base composition of the transforming virus DNA fragment indicated that the transforming DNA has a base composition approximately the same as the HSV genome and does not constitute a low GC virus DNA region. Cross hybridization between HSV-1 transformed cells and HSV-2 DNA is very slight, indicating that the DNA found in clone 139 is not entirely composed of the HSV-1 and HSV-2 common sequences.", "contents": "Quantification of the herpes simplex virus DNA present in biochemically transformed mouse cells and their revertants. Four cell lines biochemically transformed by u.v.-irradiated herpes simplex virus contain virus DNA fragments ranging from 3 to 22% of the HSV genome. Of five revertant clones selected for 3H-TdR or BrdUrd resistance, four had lost all detectable virus DNA while the fifth, selected for BrdUrd resistance, retained the entire virus fragment but there was a reduction of virus copies per cell from 5 to 1. Three 'supertransformed' revertant cell lines contained virus DNA fragments ranging from 12 to 28%. The number of virus DNA fragments per cell ranged from 1 to 5 and clearly indicated that a single copy of the virus thymidine kinase gene is adequate for biochemical transformation. The determination of the base composition of the transforming virus DNA fragment indicated that the transforming DNA has a base composition approximately the same as the HSV genome and does not constitute a low GC virus DNA region. Cross hybridization between HSV-1 transformed cells and HSV-2 DNA is very slight, indicating that the DNA found in clone 139 is not entirely composed of the HSV-1 and HSV-2 common sequences."}
{"id": "PMID:196038", "title": "Simian virus 40-Chinese hamster kidney cell interaction. IV. Enhanced virus replication in infected cells upon treatment with mitomycin C.", "content": "Chinese hamster kidney cells are semi-permissive to simian virus 40 (SV40). Exposure to mitomycin C (MC) of Chinese hamster kidney cells infected with SV40 DNA enhanced the yield of infectious virus 10- to 100-fold. This stimulation occurred whether the treatment was performed before or after infection. A simultaneous increase in the number of V antigen-synthesizing cells and virus-producing cells, as well as the virus burst size, was observed upon MC pretreatment, whereas the proportion of T antigen-synthesizing cells remained unchanged. MC pretreatment clearly stimulated virus DNA replication in SV40 virus-infected cells. Cells treated with MC exhibited an unbalanced growth pattern, with continuing protein synthesis in the absence of cell division and a markedly reduced ability to replicate the cellular DNA. These results suggest that MC enhances the permissiveness of Chinese hamster kidney cells by inducing the synthesis of a specific cellular factor(s) required for SV40 reproduction in Chinese hamster kidney cells.", "contents": "Simian virus 40-Chinese hamster kidney cell interaction. IV. Enhanced virus replication in infected cells upon treatment with mitomycin C. Chinese hamster kidney cells are semi-permissive to simian virus 40 (SV40). Exposure to mitomycin C (MC) of Chinese hamster kidney cells infected with SV40 DNA enhanced the yield of infectious virus 10- to 100-fold. This stimulation occurred whether the treatment was performed before or after infection. A simultaneous increase in the number of V antigen-synthesizing cells and virus-producing cells, as well as the virus burst size, was observed upon MC pretreatment, whereas the proportion of T antigen-synthesizing cells remained unchanged. MC pretreatment clearly stimulated virus DNA replication in SV40 virus-infected cells. Cells treated with MC exhibited an unbalanced growth pattern, with continuing protein synthesis in the absence of cell division and a markedly reduced ability to replicate the cellular DNA. These results suggest that MC enhances the permissiveness of Chinese hamster kidney cells by inducing the synthesis of a specific cellular factor(s) required for SV40 reproduction in Chinese hamster kidney cells."}
{"id": "PMID:196039", "title": "Antiviral activity in the rabbit cornea of adenine arabinoside, Ara-A 5' monophosphate, and hypoxanthine arabinoside; and interactions with adenosine deaminase inhibitor.", "content": "The multiple microtrephination technique was used in the rabbit cornea to compare the activity against herpes simplex virus (hsv) of adenine arabinoside (ara-A), ara-A 5'monophosphate (ara-AMP) and hypoxanthine arabinoside (ara-Hx), and to determine the effect of addition of adenosine deaminase inhibitor (ADAI) to each. The greatest antiviral activity was shown by ara-AMP, and the least by ara-Hx. ADAI increased the activity of ara-A but had no effect on ara-AMP or ara-Hx.", "contents": "Antiviral activity in the rabbit cornea of adenine arabinoside, Ara-A 5' monophosphate, and hypoxanthine arabinoside; and interactions with adenosine deaminase inhibitor. The multiple microtrephination technique was used in the rabbit cornea to compare the activity against herpes simplex virus (hsv) of adenine arabinoside (ara-A), ara-A 5'monophosphate (ara-AMP) and hypoxanthine arabinoside (ara-Hx), and to determine the effect of addition of adenosine deaminase inhibitor (ADAI) to each. The greatest antiviral activity was shown by ara-AMP, and the least by ara-Hx. ADAI increased the activity of ara-A but had no effect on ara-AMP or ara-Hx."}
{"id": "PMID:196048", "title": "Electrical and mechanical responses in the platysma and in the adductor pollicis muscle: in patients with myasthenia gravis.", "content": "Electrical and mechanical muscular responses to single and repetitive stimuli were recorded in 24 patients with myasthenia gravis. Findings in the platysma were compared with those in m. adductor pollicis (ADP). In the platysma, but not in the ADP, electrical and mechanical responses to single stimuli were often lower than normal, and could be normalised after tetanus and by endrophonium. The decrement of electrical and mechanical responses to repetitive stimuli was two to three times greater in the platysma than in the ADP; post-tetanic facilitation of the action potential was four times greater. The staircase phenomenon was abnormal in the platysma in patients with moderate and severe myasthenia, and also in the ADP in some patients without decrement in the action potential. Edrophonium was more effective in alleviating decrement in the platysma than in the ADP. In the platysma, block of neuromuscular transmission could account for most abnormalities. The finding in some patients of an abnormal staircase after correction for block of fibres indicates a lesion in excitation-contraction coupling. In six patients only the platysma showed abnormalities, in 10 patients abnormalities were more pronounced in the platysma than in the ADP, and in three patients more pronounced in the ADP than in the platysma; in five patients the platysma and the ADP were equally affected.", "contents": "Electrical and mechanical responses in the platysma and in the adductor pollicis muscle: in patients with myasthenia gravis. Electrical and mechanical muscular responses to single and repetitive stimuli were recorded in 24 patients with myasthenia gravis. Findings in the platysma were compared with those in m. adductor pollicis (ADP). In the platysma, but not in the ADP, electrical and mechanical responses to single stimuli were often lower than normal, and could be normalised after tetanus and by endrophonium. The decrement of electrical and mechanical responses to repetitive stimuli was two to three times greater in the platysma than in the ADP; post-tetanic facilitation of the action potential was four times greater. The staircase phenomenon was abnormal in the platysma in patients with moderate and severe myasthenia, and also in the ADP in some patients without decrement in the action potential. Edrophonium was more effective in alleviating decrement in the platysma than in the ADP. In the platysma, block of neuromuscular transmission could account for most abnormalities. The finding in some patients of an abnormal staircase after correction for block of fibres indicates a lesion in excitation-contraction coupling. In six patients only the platysma showed abnormalities, in 10 patients abnormalities were more pronounced in the platysma than in the ADP, and in three patients more pronounced in the ADP than in the platysma; in five patients the platysma and the ADP were equally affected."}
{"id": "PMID:196049", "title": "Value of exchangeable electrolyte measurement in the treatment of myasthenia gravis.", "content": "We have investigated electrolyte exchange in myasthenia gravis before and after corticotrophin therapy, using a four-isotope dilution technique. Clinical deterioration in patients on corticotrophin is associated with a fall of more than 20% in the intracellular potassium concentration, suggesting that all myasthenics so treated should be given potassium supplementation.", "contents": "Value of exchangeable electrolyte measurement in the treatment of myasthenia gravis. We have investigated electrolyte exchange in myasthenia gravis before and after corticotrophin therapy, using a four-isotope dilution technique. Clinical deterioration in patients on corticotrophin is associated with a fall of more than 20% in the intracellular potassium concentration, suggesting that all myasthenics so treated should be given potassium supplementation."}
{"id": "PMID:196050", "title": "Post-ischaemic paraesthesia in pellagrins.", "content": "A quantitative assessment of post-ischaemic paraesthesiae has been made in 50 pellagrins and 20 healthy identical controls. The results show a higly significant diminution of the paraesthetic response in pellagrins. In pellagrins having peripheral neuropathy the depression of paraesthesiae was more marked than in those without peripheral neuropathy. There was no consistent relationship between severity of peripheral neuropathy and degree of depression of paraesthetic response.", "contents": "Post-ischaemic paraesthesia in pellagrins. A quantitative assessment of post-ischaemic paraesthesiae has been made in 50 pellagrins and 20 healthy identical controls. The results show a higly significant diminution of the paraesthetic response in pellagrins. In pellagrins having peripheral neuropathy the depression of paraesthesiae was more marked than in those without peripheral neuropathy. There was no consistent relationship between severity of peripheral neuropathy and degree of depression of paraesthetic response."}
{"id": "PMID:196051", "title": "Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies.", "content": "Four patients are described who developed a peripheral neuropathy 10 days to 3 weeks after ingestion of a single dose of arsenic. All improved slowly, but after 6 to 8 years 3 of them still had abnormal neurological symptoms and signs. Electrophysiological studies showed reduction of motor conduction velocity and marked abnormalities of sensory nerve action potentials. The findings suggest that conduction is abnormal in at least some surviving nerve fibres. Sural nerve biopsies from 2 patients showed axonal degeneration, which was at an early stage in some fibres, even 10 weeks after intoxication.", "contents": "Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies. Four patients are described who developed a peripheral neuropathy 10 days to 3 weeks after ingestion of a single dose of arsenic. All improved slowly, but after 6 to 8 years 3 of them still had abnormal neurological symptoms and signs. Electrophysiological studies showed reduction of motor conduction velocity and marked abnormalities of sensory nerve action potentials. The findings suggest that conduction is abnormal in at least some surviving nerve fibres. Sural nerve biopsies from 2 patients showed axonal degeneration, which was at an early stage in some fibres, even 10 weeks after intoxication."}
{"id": "PMID:196052", "title": "Ultrastructural effects of herpes simplex virus type 2 infection of rat dorsal root ganglia in culture.", "content": "The ultrastructural consequences of herpes simplex virus type 2 (strain R-2) infection of organotypic cultures of embryonic rat dorsal root ganglia were studied. The intial consequences (dilation of endoplasmic reticulum and/or Golgi apparatus and distortion of mitochondrial structure) occurred in the cytoplasm. These effects were followed by several nuclear changes including loss of nucleoplasm, and margination of chromatin. Extensive nuclear membrane proliferation was accompanied by the viral maturation process. Two previously unreported observations were made. First, productive virus replications occurred in glial cells, as well as in neurons. Mature, enveloped virus was produced by nuclear budding and envelopment in the cytoplasm in both cell types. Second, neurons were observed to participate in polykaryocyte formation with other neurons and with glial cells. These polykaryocytes were usually composed of only three or four cells. Neuronal-glial polykaryocytes were more prevalent than neuronal-neuronal polykaryocytes. In general, however, the ultrastructural changes in neurons and glial cells in culture were consistent with previously reported changes occurring in nervous tissue of experimental animals suffering from acute herpes simplex virus infections. Therefore, the utilization of this in vitro system to further study the pathogenesis of acute herpetic infections of sensory ganglia appears to be reasonable.", "contents": "Ultrastructural effects of herpes simplex virus type 2 infection of rat dorsal root ganglia in culture. The ultrastructural consequences of herpes simplex virus type 2 (strain R-2) infection of organotypic cultures of embryonic rat dorsal root ganglia were studied. The intial consequences (dilation of endoplasmic reticulum and/or Golgi apparatus and distortion of mitochondrial structure) occurred in the cytoplasm. These effects were followed by several nuclear changes including loss of nucleoplasm, and margination of chromatin. Extensive nuclear membrane proliferation was accompanied by the viral maturation process. Two previously unreported observations were made. First, productive virus replications occurred in glial cells, as well as in neurons. Mature, enveloped virus was produced by nuclear budding and envelopment in the cytoplasm in both cell types. Second, neurons were observed to participate in polykaryocyte formation with other neurons and with glial cells. These polykaryocytes were usually composed of only three or four cells. Neuronal-glial polykaryocytes were more prevalent than neuronal-neuronal polykaryocytes. In general, however, the ultrastructural changes in neurons and glial cells in culture were consistent with previously reported changes occurring in nervous tissue of experimental animals suffering from acute herpes simplex virus infections. Therefore, the utilization of this in vitro system to further study the pathogenesis of acute herpetic infections of sensory ganglia appears to be reasonable."}
{"id": "PMID:196053", "title": "Ultrastructural findings of peripheral nerve in a preclinical case of adult metachromatic leukodystrophy.", "content": "In a 13-year-old neurologically healthy boy from a family with adult-onset of metachromatic leukodystrophy (MLD) showing arylsulfatase A-deficiency in the adult, sural nerve biopsy probably was performed 2-3 decades before clinical manifestation of the disease could be expected. Ultrastructurally 4 basic types of inclusion bodies in Schwann cells could be demonstrated (pleo-morphic \"zebra body\"-like inclusions, double-lamellated inclusions, \"tuff-stone\"-like inclusions, granular osmiophilic inclusions). Additionally, endoplasmatic reticulum, mitochondria and lysosomes showed marked alterations. Advanced damage of myelin was only rarely seen, but initial segmental demyelination was a common finding. These early pathological changes in chronic MLD are thought to represent a subcellular metabolic insufficiency of Schwann cells in this disease.", "contents": "Ultrastructural findings of peripheral nerve in a preclinical case of adult metachromatic leukodystrophy. In a 13-year-old neurologically healthy boy from a family with adult-onset of metachromatic leukodystrophy (MLD) showing arylsulfatase A-deficiency in the adult, sural nerve biopsy probably was performed 2-3 decades before clinical manifestation of the disease could be expected. Ultrastructurally 4 basic types of inclusion bodies in Schwann cells could be demonstrated (pleo-morphic \"zebra body\"-like inclusions, double-lamellated inclusions, \"tuff-stone\"-like inclusions, granular osmiophilic inclusions). Additionally, endoplasmatic reticulum, mitochondria and lysosomes showed marked alterations. Advanced damage of myelin was only rarely seen, but initial segmental demyelination was a common finding. These early pathological changes in chronic MLD are thought to represent a subcellular metabolic insufficiency of Schwann cells in this disease."}
{"id": "PMID:196054", "title": "Spontaneous slow potentials and spreading depression in amphibian retina.", "content": "1. In frog and mudpuppy eye cups perfused with low-chloride solution, two types of slow potential phenomena were studied. One type, \"spontaneous slow potentials\" (SSPs), appeared both in the dark and during light stimuli. The other type, the slow potential change (SPC) of spreading depression (SD), appeared at termination of long-duration light stimuli. 2. The SSPs were analyzed by depth-profile studies, pharmacologic studies, and the use of potassium-specific electrodes. Results indicated that SSPs may represent spontaneous d-waves that travel across the retina. The SSPs are associated with potassium activity, and the main response is probably generated by M\u00fcller cells. Initiation and/or propagation appear to require chemically mediated synaptic transmission and impulse activity. 3. Depth-profile studies were also done of the SPC of SD induced by termination of long-duration light stimuli. Results indicated that the SPC is not an exaggerated d-wave. The SPC consists of two components, the second of which reverses more superficially than the d-wave. The main SPC response is probably generated by M\u00fcller cells. Although impulse activity does not appear to be necessary for SD, it may contribute to this complex response.", "contents": "Spontaneous slow potentials and spreading depression in amphibian retina. 1. In frog and mudpuppy eye cups perfused with low-chloride solution, two types of slow potential phenomena were studied. One type, \"spontaneous slow potentials\" (SSPs), appeared both in the dark and during light stimuli. The other type, the slow potential change (SPC) of spreading depression (SD), appeared at termination of long-duration light stimuli. 2. The SSPs were analyzed by depth-profile studies, pharmacologic studies, and the use of potassium-specific electrodes. Results indicated that SSPs may represent spontaneous d-waves that travel across the retina. The SSPs are associated with potassium activity, and the main response is probably generated by M\u00fcller cells. Initiation and/or propagation appear to require chemically mediated synaptic transmission and impulse activity. 3. Depth-profile studies were also done of the SPC of SD induced by termination of long-duration light stimuli. Results indicated that the SPC is not an exaggerated d-wave. The SPC consists of two components, the second of which reverses more superficially than the d-wave. The main SPC response is probably generated by M\u00fcller cells. Although impulse activity does not appear to be necessary for SD, it may contribute to this complex response."}
{"id": "PMID:196056", "title": "Neuromuscular transmission in dystrophic mice.", "content": "1. Neuromuscular transmission was studied in the extensor digitorum-longus muscle of dystrophic mice (strain 129/ReJ) by means of intracellular recording techniques. 2. In a large population of normal and dystrophic muscle fibers tested, the incidence of transmission failure was about 2% and showed no significant difference between the two groups. 3. Quantal size and quantum content of dystrophic junctions were found to be normal. This was true even of nerve terminal on apparently atrophied muscle fibers. 4. The facilitation ratio at dystrophic junctions was not significantly different from normal. 5. Dystrophic neuromuscular junctions exhibited an abnormality high frequency of giant spontaneous potentials. Application of tetrodotoxin (10(-6) M) and curare (10(-6) M) indicated that these potentials were caused by impulse-independent release of acetylcholine. 6. Neuromuscular transmission in dystrophic mice was found functionally normal and unrelated to the degenerative state of the muscle.", "contents": "Neuromuscular transmission in dystrophic mice. 1. Neuromuscular transmission was studied in the extensor digitorum-longus muscle of dystrophic mice (strain 129/ReJ) by means of intracellular recording techniques. 2. In a large population of normal and dystrophic muscle fibers tested, the incidence of transmission failure was about 2% and showed no significant difference between the two groups. 3. Quantal size and quantum content of dystrophic junctions were found to be normal. This was true even of nerve terminal on apparently atrophied muscle fibers. 4. The facilitation ratio at dystrophic junctions was not significantly different from normal. 5. Dystrophic neuromuscular junctions exhibited an abnormality high frequency of giant spontaneous potentials. Application of tetrodotoxin (10(-6) M) and curare (10(-6) M) indicated that these potentials were caused by impulse-independent release of acetylcholine. 6. Neuromuscular transmission in dystrophic mice was found functionally normal and unrelated to the degenerative state of the muscle."}
{"id": "PMID:196058", "title": "Effect of high-oleic and high-linoleic safflower oils on mammary tumors induced in rats by 7,12-dimethylbenz(alpha)anthracene.", "content": "A mutant safflower oil, rich in oleic acid, was used for a critical test of the hypothesis that polyunsaturated fats act as co-carcinogens. Weanling female rats were each given 5 mg of 7,12-dimethylbenz(alpha)anthracene. They were then pair-fed diets containing 20%, by weight, of conventional high-linoleic safflower oil; a mutant high-oleic safflower oil; or coconut oil. Half of each group received supplementary DL-alpha-tocopherol. Tumors were identified by two observers, by palpation. Data on incidence of tumors and on numbers of tumors per affected rat led to similar conclusions. At 16 weeks, there were significant differences when supplementary tocopherol was included in the diet: the group fed high-oleic safflower oil had more tumors than the group fed coconut oil. This difference was not seen in the absence of supplementary tocopherol. When the data for tocopherol-supplemented and unsupplemented subgroups were combined, the high-oleic safflower oil group had significantly more tumors than did the coconut oil group. The high-linoleic safflower oil group was not significantly different from either of the other groups. In all groups, histologic examination of the largest tumor in each rat revealed more benign tumors, mostly duct papillomas, than carcinomas.", "contents": "Effect of high-oleic and high-linoleic safflower oils on mammary tumors induced in rats by 7,12-dimethylbenz(alpha)anthracene. A mutant safflower oil, rich in oleic acid, was used for a critical test of the hypothesis that polyunsaturated fats act as co-carcinogens. Weanling female rats were each given 5 mg of 7,12-dimethylbenz(alpha)anthracene. They were then pair-fed diets containing 20%, by weight, of conventional high-linoleic safflower oil; a mutant high-oleic safflower oil; or coconut oil. Half of each group received supplementary DL-alpha-tocopherol. Tumors were identified by two observers, by palpation. Data on incidence of tumors and on numbers of tumors per affected rat led to similar conclusions. At 16 weeks, there were significant differences when supplementary tocopherol was included in the diet: the group fed high-oleic safflower oil had more tumors than the group fed coconut oil. This difference was not seen in the absence of supplementary tocopherol. When the data for tocopherol-supplemented and unsupplemented subgroups were combined, the high-oleic safflower oil group had significantly more tumors than did the coconut oil group. The high-linoleic safflower oil group was not significantly different from either of the other groups. In all groups, histologic examination of the largest tumor in each rat revealed more benign tumors, mostly duct papillomas, than carcinomas."}
{"id": "PMID:196059", "title": "Phagocytosis and leukocyte enzymes in ascorbic acid deficient guinea pigs.", "content": "Enzymes related to bactericidal activities of leukocytes were studied in ascorbic acid deficient guinea pig leukocytes. The activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were not affected either under resting or phagocytizing conditions in ascorbic acid deficiency. Granule bound NADPH-oxidase activity of resting leukocytes also was not altered in ascorbic acid deficiency. However, the extent of stimulation in NADPH-oxidase activity under phagocytizing condition was found to be significantly lower in ascorbic acid deficient leukocytes than that in control leukocytes. Similary, the extent of release of acid phosphatase from lysosomes during phagocytosis was also low in ascorbic acid deficient leukocytes. Ascorbic acid deficiency did not influence the activities of glutathione reductase and myeloperoxidase of leukocytes. The significance of these enzyme changes is discussed in relation to the decreased phagocytic and bactericidal activities of leukocytes in ascorbic acid deficiency.", "contents": "Phagocytosis and leukocyte enzymes in ascorbic acid deficient guinea pigs. Enzymes related to bactericidal activities of leukocytes were studied in ascorbic acid deficient guinea pig leukocytes. The activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were not affected either under resting or phagocytizing conditions in ascorbic acid deficiency. Granule bound NADPH-oxidase activity of resting leukocytes also was not altered in ascorbic acid deficiency. However, the extent of stimulation in NADPH-oxidase activity under phagocytizing condition was found to be significantly lower in ascorbic acid deficient leukocytes than that in control leukocytes. Similary, the extent of release of acid phosphatase from lysosomes during phagocytosis was also low in ascorbic acid deficient leukocytes. Ascorbic acid deficiency did not influence the activities of glutathione reductase and myeloperoxidase of leukocytes. The significance of these enzyme changes is discussed in relation to the decreased phagocytic and bactericidal activities of leukocytes in ascorbic acid deficiency."}
{"id": "PMID:196060", "title": "Altered enzyme release by virus infected mouse salivary glands.", "content": "The rates of release of salivary amylase and esterase from normal and polyoma virus infected mouse submandibular glands were measured in a continuous flow perifusion system. Following stimulation by epinephrine, the rate of release of esterase by the infected glands was significantly greater than that from control glands. The rate of amylase release, while greater from infected glands, was not significantly different. The total enzyme contents from infected and control tissues were similar. Cyclic GMP was found to be higher in the infected glands than the control glands, suggesting one possible mechanism for the higher rates of enzyme release by infected tissues.", "contents": "Altered enzyme release by virus infected mouse salivary glands. The rates of release of salivary amylase and esterase from normal and polyoma virus infected mouse submandibular glands were measured in a continuous flow perifusion system. Following stimulation by epinephrine, the rate of release of esterase by the infected glands was significantly greater than that from control glands. The rate of amylase release, while greater from infected glands, was not significantly different. The total enzyme contents from infected and control tissues were similar. Cyclic GMP was found to be higher in the infected glands than the control glands, suggesting one possible mechanism for the higher rates of enzyme release by infected tissues."}
{"id": "PMID:196061", "title": "Ultrastructural evidence for neural crest origin of the malanotic neuroectodermal tumor of infancy.", "content": "A case of malanotic neuroectodermal tumor of infancy, which occurred in the anterior maxilla of a 3-month-old girl, was studied by  electron microscopy. Polymorphic cellular elements were revealed to be present: large melanin-producing cells with some of the characteristics of a neuroepithelium, small non-pigmented cells resembling immature neuroblasts, and many intermediate forms resembling differentiating neuroblasts. All cell types clearly demonstrated ultrastructural features of neurogenic cells, e.g. neurite-like cytoplasmic processes, fine filaments and microtubules indistinguishable from those seen in normal neurites, synaptic-like structures, and neurosecretory-like vesicles. Based on these fine structures, the lesion was presumed to represent a hamartoma of primitive neuroectodermal cells with a tendency toward the differentiation into melanin-producing cells. The neural crest origin of this tumor was convincingly supported by ultrastructural analysis.", "contents": "Ultrastructural evidence for neural crest origin of the malanotic neuroectodermal tumor of infancy. A case of malanotic neuroectodermal tumor of infancy, which occurred in the anterior maxilla of a 3-month-old girl, was studied by  electron microscopy. Polymorphic cellular elements were revealed to be present: large melanin-producing cells with some of the characteristics of a neuroepithelium, small non-pigmented cells resembling immature neuroblasts, and many intermediate forms resembling differentiating neuroblasts. All cell types clearly demonstrated ultrastructural features of neurogenic cells, e.g. neurite-like cytoplasmic processes, fine filaments and microtubules indistinguishable from those seen in normal neurites, synaptic-like structures, and neurosecretory-like vesicles. Based on these fine structures, the lesion was presumed to represent a hamartoma of primitive neuroectodermal cells with a tendency toward the differentiation into melanin-producing cells. The neural crest origin of this tumor was convincingly supported by ultrastructural analysis."}
{"id": "PMID:196062", "title": "The relation of cyclic AMP levels to phagocytosis and enzyme release in acute inflammation in vivo.", "content": "The effect of altering endogenous leucocyte cyclic AMP levels on phagocytosis and lysosomal enzyme release was studied in vivo. Acute pleural exudates were produced in rats using either calcium pyrophosphate dihydrate crystals or rat serum. Despite marked increases in leucocyte cyclic AMP concentration produced by injection of dibutyryl cyclic AMP and theophylline, there was no reduction in crystal phagocytosis or in enzyme discharge.", "contents": "The relation of cyclic AMP levels to phagocytosis and enzyme release in acute inflammation in vivo. The effect of altering endogenous leucocyte cyclic AMP levels on phagocytosis and lysosomal enzyme release was studied in vivo. Acute pleural exudates were produced in rats using either calcium pyrophosphate dihydrate crystals or rat serum. Despite marked increases in leucocyte cyclic AMP concentration produced by injection of dibutyryl cyclic AMP and theophylline, there was no reduction in crystal phagocytosis or in enzyme discharge."}
{"id": "PMID:196063", "title": "Pathology of ovine adenovirus type 4 infection in SPF lambs: pulmonary and hepatic lesions.", "content": "Seven lambs were challenged with an aerosol of OA4 virus. Four developed mild pulmonary oedema and a sparse accumulation of mononuclear cells around blood vessels similar to results reported previously. In addition, three had focal hepatic necrosis and one of these three had a non-suppurative occlusive cholangitis and portal tract lymphangitis and thrombosis. Basophilic intranuclear IB's were identified in many necrotic hepatocytes, in lymphatic endothelial cells involved in thrombi but in only one bile duct epithelial cell. Ultrastructurally, virions with the characteristics of adenovirus were seen in hepatocytes. Although only one IB was seen in the affected biliary system there was no evidence that it was caused by an agent other than OA4. Virus was considered to infect the respiratory system directly, be swallowed to infect the alimentary system and carried, possibly within cells, via a haematogeneous and/or lymphogenous route to the liver. The effect of naturally acquired virus on sheep is unknown but it is possible that it may predispose the host to more serious infections.", "contents": "Pathology of ovine adenovirus type 4 infection in SPF lambs: pulmonary and hepatic lesions. Seven lambs were challenged with an aerosol of OA4 virus. Four developed mild pulmonary oedema and a sparse accumulation of mononuclear cells around blood vessels similar to results reported previously. In addition, three had focal hepatic necrosis and one of these three had a non-suppurative occlusive cholangitis and portal tract lymphangitis and thrombosis. Basophilic intranuclear IB's were identified in many necrotic hepatocytes, in lymphatic endothelial cells involved in thrombi but in only one bile duct epithelial cell. Ultrastructurally, virions with the characteristics of adenovirus were seen in hepatocytes. Although only one IB was seen in the affected biliary system there was no evidence that it was caused by an agent other than OA4. Virus was considered to infect the respiratory system directly, be swallowed to infect the alimentary system and carried, possibly within cells, via a haematogeneous and/or lymphogenous route to the liver. The effect of naturally acquired virus on sheep is unknown but it is possible that it may predispose the host to more serious infections."}
{"id": "PMID:196064", "title": "Electrical excitability of oat cell carcinoma.", "content": "Cultured tumour cells from two oat cell carcinomas of the lung were demonstrated to generate all-or-nothing, short-duration action potentials similar to those previously reported in neurones, in bronchial carcinoid cells, and in a number of endocrine cells of proven or proposed neural ancestry. This observation provides new evidence to establish oat cell carcinomas and carcinoids as closely related tumours distinct from other pulmonary neoplasms, and raises the possibility of treating these tumours by manipulation of hormonal agents.", "contents": "Electrical excitability of oat cell carcinoma. Cultured tumour cells from two oat cell carcinomas of the lung were demonstrated to generate all-or-nothing, short-duration action potentials similar to those previously reported in neurones, in bronchial carcinoid cells, and in a number of endocrine cells of proven or proposed neural ancestry. This observation provides new evidence to establish oat cell carcinomas and carcinoids as closely related tumours distinct from other pulmonary neoplasms, and raises the possibility of treating these tumours by manipulation of hormonal agents."}
{"id": "PMID:196065", "title": "Schistosoma mansoni: ultrastructural studies on the esophageal secretory granules.", "content": "The posterior portion of the esophageal gland of Schistosoma mansoni produces a granule that is highly structured internally. Each granule consists of arrays of membrane-bound tubules enclosed by a membrane. Cytochemical tests indicate that the granules are not reactive for cytochrome c-oxidase but du react for macromolecular carbohydrates. It is believed that the granules are synthesized in the Golgi complex and are secreted at the base of the luminal amplifications of the esophagus. Colchicine treatment results in an accumulation of granules in the cyton region. Their physiological function is still undetermined, but it is hypothesized that they are involved with early stages of digestion of host red blood cells.", "contents": "Schistosoma mansoni: ultrastructural studies on the esophageal secretory granules. The posterior portion of the esophageal gland of Schistosoma mansoni produces a granule that is highly structured internally. Each granule consists of arrays of membrane-bound tubules enclosed by a membrane. Cytochemical tests indicate that the granules are not reactive for cytochrome c-oxidase but du react for macromolecular carbohydrates. It is believed that the granules are synthesized in the Golgi complex and are secreted at the base of the luminal amplifications of the esophagus. Colchicine treatment results in an accumulation of granules in the cyton region. Their physiological function is still undetermined, but it is hypothesized that they are involved with early stages of digestion of host red blood cells."}
{"id": "PMID:196068", "title": "Facilitatory and inhibitory effects of gamma-aminobutyric acid on ganglionic transmission in the sympathetic cardiac nerves of the dog.", "content": "Effects of gamma-aminobutyric acid (GABA) on ganglionic transmission in the peripheral course of the sympathetic cardiac nerves were investigated in vagotomized and cardiac decentralized open-chest dogs. GABA (1-300 microgram/kg) was given i.v. during electrical stimulation of pre-or postganglionic fibers which induced a sustained acceleration of sinus rate. GABA in small doses of 1 and 3 microgram/kg augmented the sinus acceleration during electrical stimulation of the ansa subclavia which largely consists of preganglionic fibers, but depressed the sinus acceleration in large doses over 30 microgram/kg. With a dose of a 10 microgram/kg, its effect was dual and varied from preparation to preparation. On the other hand, GABA did not modify basal heart rate or the increase in heart rate in response to stimulation of the stellate cardiac nerve postganglionic fibers. These results clearly demonstrated dual effects of GABA on ganglionic transmission, i.e., facilitation in small doses and depression in large doses. The depression caused by large doses of GABA was markedly reduced by picrotoxin, 1 mg/kg, while the facilitation remained unaffected. Treatment with atropine, 1 mg/kg, and phenozy-benzamine, 1 mg/kg, failed to influence the effects of GABA. The possible mechanisms for these effects of GABA are discussed.", "contents": "Facilitatory and inhibitory effects of gamma-aminobutyric acid on ganglionic transmission in the sympathetic cardiac nerves of the dog. Effects of gamma-aminobutyric acid (GABA) on ganglionic transmission in the peripheral course of the sympathetic cardiac nerves were investigated in vagotomized and cardiac decentralized open-chest dogs. GABA (1-300 microgram/kg) was given i.v. during electrical stimulation of pre-or postganglionic fibers which induced a sustained acceleration of sinus rate. GABA in small doses of 1 and 3 microgram/kg augmented the sinus acceleration during electrical stimulation of the ansa subclavia which largely consists of preganglionic fibers, but depressed the sinus acceleration in large doses over 30 microgram/kg. With a dose of a 10 microgram/kg, its effect was dual and varied from preparation to preparation. On the other hand, GABA did not modify basal heart rate or the increase in heart rate in response to stimulation of the stellate cardiac nerve postganglionic fibers. These results clearly demonstrated dual effects of GABA on ganglionic transmission, i.e., facilitation in small doses and depression in large doses. The depression caused by large doses of GABA was markedly reduced by picrotoxin, 1 mg/kg, while the facilitation remained unaffected. Treatment with atropine, 1 mg/kg, and phenozy-benzamine, 1 mg/kg, failed to influence the effects of GABA. The possible mechanisms for these effects of GABA are discussed."}
{"id": "PMID:196069", "title": "Antiproliferative activity of anti-inflammatory drugs in two mammalian cell culture lines.", "content": "The nonsteroid anti-inflammatory drugs inhibited cell proliferation when added to rat hepatoma and human fibroblast cultures. The inhibition was reversible; normal growth resumed when the cultures were washed free of drug. Protein and nucleic acid synthesis, as measured by isotope incorporation was also reduced, although this reduction was probably a reflection of the decrease in cell numbers. An exception was that, in low concentration, the salicylate drugs, salicylamide, salicylic acid and aspirin, stimulated protein and nucleic acid synthesis, but in high concentrations (greater than 1 mM) they inhibited culture growth as well as protein and nucleic acid synthesis. Pharmacologically inactive derivatives, such as m-hydroxybenzoic acid and gentisic acid, were not inhibitory in concentrations up to 5 mM. The order of potency in inhibiting culture growth, meclofenamate greater than indomethacin greater than salicylamide greater than phenylbutazone greater than phenacetin greater than aspirin = salicylic acid, was similar to that reported for their anti-inflammator activity and their ability to inhibit prostaglandin synthesis. The antiproliferative activity of these drugs may, in part, account for their anti-inflammatory and toxic actions in vivo.", "contents": "Antiproliferative activity of anti-inflammatory drugs in two mammalian cell culture lines. The nonsteroid anti-inflammatory drugs inhibited cell proliferation when added to rat hepatoma and human fibroblast cultures. The inhibition was reversible; normal growth resumed when the cultures were washed free of drug. Protein and nucleic acid synthesis, as measured by isotope incorporation was also reduced, although this reduction was probably a reflection of the decrease in cell numbers. An exception was that, in low concentration, the salicylate drugs, salicylamide, salicylic acid and aspirin, stimulated protein and nucleic acid synthesis, but in high concentrations (greater than 1 mM) they inhibited culture growth as well as protein and nucleic acid synthesis. Pharmacologically inactive derivatives, such as m-hydroxybenzoic acid and gentisic acid, were not inhibitory in concentrations up to 5 mM. The order of potency in inhibiting culture growth, meclofenamate greater than indomethacin greater than salicylamide greater than phenylbutazone greater than phenacetin greater than aspirin = salicylic acid, was similar to that reported for their anti-inflammator activity and their ability to inhibit prostaglandin synthesis. The antiproliferative activity of these drugs may, in part, account for their anti-inflammatory and toxic actions in vivo."}
{"id": "PMID:196070", "title": "The synergistic action of L-glutamate and L-aspartate at crustacean excitatory neuromuscular junctions.", "content": "1. When L-glutamate and L-aspartate are simultaneously applied to the excitatory neuromuscular junctions of Maia squinado, they produce an increase in the conductance of the post-synaptic membrane much larger than the sum of conductance effects produced by the individual amino acids alone. 2. An examination of the synaptic noise occurring during this synergistic action reveals that the elementary conductnace events produced by aspartate are suppressed and that normal elementary conductance events produced by glutamate are occurring at an enormously increased rate. 3. It is suggested that aspartate causes this potentiation by inhibiting a system for transmitter inactivation in the region of the post-synaptic receptors and that this system, under normal conditions, prevents the access of externally applied glutamate to the synaptic receptors.", "contents": "The synergistic action of L-glutamate and L-aspartate at crustacean excitatory neuromuscular junctions. 1. When L-glutamate and L-aspartate are simultaneously applied to the excitatory neuromuscular junctions of Maia squinado, they produce an increase in the conductance of the post-synaptic membrane much larger than the sum of conductance effects produced by the individual amino acids alone. 2. An examination of the synaptic noise occurring during this synergistic action reveals that the elementary conductnace events produced by aspartate are suppressed and that normal elementary conductance events produced by glutamate are occurring at an enormously increased rate. 3. It is suggested that aspartate causes this potentiation by inhibiting a system for transmitter inactivation in the region of the post-synaptic receptors and that this system, under normal conditions, prevents the access of externally applied glutamate to the synaptic receptors."}
{"id": "PMID:196071", "title": "The termination of transmitter action at the crustacean excitatory neuromuscular junction.", "content": "1. Excitatory junctional currents (e.j.c.s) and miniature excitatory junctional currents (mine.e.j.c.s) have been followed by recording the focal extracellular potential at excitatory neuromuscular junctions of Maia squinado, the Spider Crab. 2. If L-aspartate (concentrations less than or equal to 1 mM) is present in the saline, the average e.j.c. is prolonged by an increase in the duration of its falling phase. 3. No change occurs in the time course of the probablility of release of quanta in the e.j.c. as determined from the histogram of first quantal latencies. 4. The min.e.j.c. is also prolonged by L-aspartate (concentrations less than or equal to 0-5 mM). The rise time increases slightly, the pre-exponential period of the decay phase almost doubles, and the time constant of the final exponential decay increases to a value larger than the average lifetime of the elementary conductance event produced by L-glutamate. 5. Changes in e.j.c.s and min.e.j.c.s produced by aspartate show a striking similarity to the action of neostigmine on the time course of the vertebrate end-plate current. It is proposed that aspartate exerts its action by blocking a process normally reponsible for clearing the synaptic cleft of transmitter.", "contents": "The termination of transmitter action at the crustacean excitatory neuromuscular junction. 1. Excitatory junctional currents (e.j.c.s) and miniature excitatory junctional currents (mine.e.j.c.s) have been followed by recording the focal extracellular potential at excitatory neuromuscular junctions of Maia squinado, the Spider Crab. 2. If L-aspartate (concentrations less than or equal to 1 mM) is present in the saline, the average e.j.c. is prolonged by an increase in the duration of its falling phase. 3. No change occurs in the time course of the probablility of release of quanta in the e.j.c. as determined from the histogram of first quantal latencies. 4. The min.e.j.c. is also prolonged by L-aspartate (concentrations less than or equal to 0-5 mM). The rise time increases slightly, the pre-exponential period of the decay phase almost doubles, and the time constant of the final exponential decay increases to a value larger than the average lifetime of the elementary conductance event produced by L-glutamate. 5. Changes in e.j.c.s and min.e.j.c.s produced by aspartate show a striking similarity to the action of neostigmine on the time course of the vertebrate end-plate current. It is proposed that aspartate exerts its action by blocking a process normally reponsible for clearing the synaptic cleft of transmitter."}
{"id": "PMID:196082", "title": "Membranous localization and properties of ATPase of rat liver lysosomes.", "content": "Lysosomes isolated from rat liver were found to have ATPase activity (EC No 3.6.1.3). Subfractionation of the lysosomes revealed a membranous localization of ATPase activity. The enzyme has half maximal activity at 0.2 mM ATP and is inhibited by high concentrations of ATP. The apparent Km for divalent metal is 0.2 mM, and either Ca2+ or Mg2+ give maximal activity. The ATPase activity has latency when lysosomes are isolated from rats treated with Triton WR-1339. This latency may be due to the presence of internalized sucrose because the activity of L fraction lysosomes is much less latent and Triton WR-1339 itself is not inhibitory. The latency of glucosaminidase, a marker enzyme for lysosomes, contrasts with the low latency of the ATPase and points to an ATPase with an exposed active site in intact lysosomes.", "contents": "Membranous localization and properties of ATPase of rat liver lysosomes. Lysosomes isolated from rat liver were found to have ATPase activity (EC No 3.6.1.3). Subfractionation of the lysosomes revealed a membranous localization of ATPase activity. The enzyme has half maximal activity at 0.2 mM ATP and is inhibited by high concentrations of ATP. The apparent Km for divalent metal is 0.2 mM, and either Ca2+ or Mg2+ give maximal activity. The ATPase activity has latency when lysosomes are isolated from rats treated with Triton WR-1339. This latency may be due to the presence of internalized sucrose because the activity of L fraction lysosomes is much less latent and Triton WR-1339 itself is not inhibitory. The latency of glucosaminidase, a marker enzyme for lysosomes, contrasts with the low latency of the ATPase and points to an ATPase with an exposed active site in intact lysosomes."}
{"id": "PMID:196083", "title": "Growth rate of cultured Novikoff rat hepatoma cells as a function of the rate of thymidine and hypoxanthine transport.", "content": "Novikoff rat hepatoma cells were propagated in suspension culture in the presence of 1 micron methotrexate and various concentrations of hypoxanthine (or adenosine plus guanosine) and thymidine and with or without the inhibitor of nucleoside and purine transport, Persantin (dipyridamole). Methotrexate-treated cells failed to replicate and died even if the medium was supplemented with either thymidine or a purine source, but normal replication occurred when both were present. The additional presence of Persantin reduced the rate of transport of thymidine or hypoxanthine and thus their incorporation into the nucleotide pool and decreased the rate of cell replication. The growth rate of the cells was directly proportional to the rate of incorporation of thymidine (in the presence of excess hypoxanthine) or of hypoxanthine (in the presence of excess thymidine) until the normal maximum growth rate was obtained. Normal cell replication in the presence of methotrexate and Persantin occurred only when the medium was supplemented with 500 micron hypoxanthine and 30 micron thymidine. The results illustrate a dependence of the growth rate of mammalian cells on the rate of transport of essential nutrients into the cell.", "contents": "Growth rate of cultured Novikoff rat hepatoma cells as a function of the rate of thymidine and hypoxanthine transport. Novikoff rat hepatoma cells were propagated in suspension culture in the presence of 1 micron methotrexate and various concentrations of hypoxanthine (or adenosine plus guanosine) and thymidine and with or without the inhibitor of nucleoside and purine transport, Persantin (dipyridamole). Methotrexate-treated cells failed to replicate and died even if the medium was supplemented with either thymidine or a purine source, but normal replication occurred when both were present. The additional presence of Persantin reduced the rate of transport of thymidine or hypoxanthine and thus their incorporation into the nucleotide pool and decreased the rate of cell replication. The growth rate of the cells was directly proportional to the rate of incorporation of thymidine (in the presence of excess hypoxanthine) or of hypoxanthine (in the presence of excess thymidine) until the normal maximum growth rate was obtained. Normal cell replication in the presence of methotrexate and Persantin occurred only when the medium was supplemented with 500 micron hypoxanthine and 30 micron thymidine. The results illustrate a dependence of the growth rate of mammalian cells on the rate of transport of essential nutrients into the cell."}
{"id": "PMID:196084", "title": "Divalent cation binding to phospholipids: an EPR study.", "content": "Divalent cation association to sonicated phospholipid liposomes has been examined with electron paramagnetic spectroscopy. Spectra were obtained suggesting that, in some cases, divalent cations associated with acidic phospholipid head groups are highly mobile. Using the amplitude of its characteristic sextet signal as a measure of free Mn(H2O)+6+, the apparent affinities of cardiolipin and phosphatidylserine for Mn2+ were measured as a function of monovalent electrolyte. Monovalent cations having smaller nonhydrated radii were more effective in displacing Mn from the phospholipids. Under conditions of low divalent cation concentrations, it is shown that the Gouy-Chapman diffuse double layer theory predicts a Mn-affinity (KA) inversely proportional to the square of monovalent salt concentration. Although this relationship was closely obeyed for Mn binding to cardiolipin, the fall-off in KA with added sodium chloride was slower in the cases of Mn binding to phosphatidylserin or phosphatidic acid. When phosphatidylcholine or cholesterol was incorporated into mixed vesicles along with a fixed amount of charged phospholipid, the Mn-binding strength was roughly proportional to the weight fraction of the latter. This result is consistent with: (1) a random dispersal of lipids in the bilayer, and (2) a 1:2 divalent cation-phospholipid interaction.", "contents": "Divalent cation binding to phospholipids: an EPR study. Divalent cation association to sonicated phospholipid liposomes has been examined with electron paramagnetic spectroscopy. Spectra were obtained suggesting that, in some cases, divalent cations associated with acidic phospholipid head groups are highly mobile. Using the amplitude of its characteristic sextet signal as a measure of free Mn(H2O)+6+, the apparent affinities of cardiolipin and phosphatidylserine for Mn2+ were measured as a function of monovalent electrolyte. Monovalent cations having smaller nonhydrated radii were more effective in displacing Mn from the phospholipids. Under conditions of low divalent cation concentrations, it is shown that the Gouy-Chapman diffuse double layer theory predicts a Mn-affinity (KA) inversely proportional to the square of monovalent salt concentration. Although this relationship was closely obeyed for Mn binding to cardiolipin, the fall-off in KA with added sodium chloride was slower in the cases of Mn binding to phosphatidylserin or phosphatidic acid. When phosphatidylcholine or cholesterol was incorporated into mixed vesicles along with a fixed amount of charged phospholipid, the Mn-binding strength was roughly proportional to the weight fraction of the latter. This result is consistent with: (1) a random dispersal of lipids in the bilayer, and (2) a 1:2 divalent cation-phospholipid interaction."}
{"id": "PMID:196085", "title": "Differences between resting and insulin-stimulated amino acid transport in frog skeletal muscle.", "content": "We have compared some features of the resting and the insulin-stimulated uptake of alpha-aminoisobutyrate (AIB) in frog skeletal muscle. We found a substantial difference between the two processes, namely, that resting AIB uptake is Na-independent while the insulin-stimulated fraction of the AIB uptake is Na-dependent. Since the amino acid transport systems in frog skeletal muscle are poorly characterized, we have also surveyed some of their properties. One of the most interesting findings of this survey is that both the uptake and efflux of AIB are inhibited by low concentrations of PCMBS (parachloro-mercury-benzene sulfonic acid 5 X 10(-5) M). In contrast, the carrier mediated transport of basic amino acids is neither inhibited by this mercurial agent nor accelerated by insulin. The action of PCMBS strongly suggests the presence of a critical sulfhydryl group in the amino acid carrier system utilized by AIB. This group is exposed to the outside solution since PCMBS penetrates cell membranes poorly, and in addition its inhibitory actions were reverted by agents that do not penetrate the cell membrane like albumin or glutathione.", "contents": "Differences between resting and insulin-stimulated amino acid transport in frog skeletal muscle. We have compared some features of the resting and the insulin-stimulated uptake of alpha-aminoisobutyrate (AIB) in frog skeletal muscle. We found a substantial difference between the two processes, namely, that resting AIB uptake is Na-independent while the insulin-stimulated fraction of the AIB uptake is Na-dependent. Since the amino acid transport systems in frog skeletal muscle are poorly characterized, we have also surveyed some of their properties. One of the most interesting findings of this survey is that both the uptake and efflux of AIB are inhibited by low concentrations of PCMBS (parachloro-mercury-benzene sulfonic acid 5 X 10(-5) M). In contrast, the carrier mediated transport of basic amino acids is neither inhibited by this mercurial agent nor accelerated by insulin. The action of PCMBS strongly suggests the presence of a critical sulfhydryl group in the amino acid carrier system utilized by AIB. This group is exposed to the outside solution since PCMBS penetrates cell membranes poorly, and in addition its inhibitory actions were reverted by agents that do not penetrate the cell membrane like albumin or glutathione."}
{"id": "PMID:196086", "title": "ATPase and phosphatase activities from human red cell membranes: I. The effects of N-ethylmaleimide.", "content": "In human red cell membranes the sensitivity to N-ethylmaleimide of Ca2+-dependent ATPase and phosphatase activities is at least ten times larger than the sensitivity to N-ethylmaleimide of (Na+ + K+)-ATPase and K+-activated phosphatase activities. All activities are partially protected against N-ethylmaleimide by ATP but not by inorganic phosphate or by p-nitrophenylphosphate. (ii) Protection by ATP of (Na+ + K+)-ATPase is impeded by either Na+ or K+ whereas only K+ impedes protection by ATP of K+-activated phosphatase. On the other hand, Na+ or K+ slightly protects Ca2+-dependent activities against N-ethylmaleimide, this effect being independent of ATP. (iii) The sensitivity to N-ethylmaleimide of Ca2+-dependent ATPase and phosphatase activities is markedly enhanced by low concentrations of Ca2+. This effect is half-maximal at less than 1 micron Ca2+ and does not require ATP, which suggests that sites with high affinity for Ca2+ exist in the Ca2+-ATPase in the absence of ATP. (IV) Under all conditions tested the response to N-ethylmaleimide of the ATPase and phosphatase activities stimulated by K+ or Na+ in the presence of Ca2+ parallels that of the Ca2+-dependent activities, suggesting that the Ca2+-ATPase system possesses sites at which monovalent cations bind to increase its activity.", "contents": "ATPase and phosphatase activities from human red cell membranes: I. The effects of N-ethylmaleimide. In human red cell membranes the sensitivity to N-ethylmaleimide of Ca2+-dependent ATPase and phosphatase activities is at least ten times larger than the sensitivity to N-ethylmaleimide of (Na+ + K+)-ATPase and K+-activated phosphatase activities. All activities are partially protected against N-ethylmaleimide by ATP but not by inorganic phosphate or by p-nitrophenylphosphate. (ii) Protection by ATP of (Na+ + K+)-ATPase is impeded by either Na+ or K+ whereas only K+ impedes protection by ATP of K+-activated phosphatase. On the other hand, Na+ or K+ slightly protects Ca2+-dependent activities against N-ethylmaleimide, this effect being independent of ATP. (iii) The sensitivity to N-ethylmaleimide of Ca2+-dependent ATPase and phosphatase activities is markedly enhanced by low concentrations of Ca2+. This effect is half-maximal at less than 1 micron Ca2+ and does not require ATP, which suggests that sites with high affinity for Ca2+ exist in the Ca2+-ATPase in the absence of ATP. (IV) Under all conditions tested the response to N-ethylmaleimide of the ATPase and phosphatase activities stimulated by K+ or Na+ in the presence of Ca2+ parallels that of the Ca2+-dependent activities, suggesting that the Ca2+-ATPase system possesses sites at which monovalent cations bind to increase its activity."}
{"id": "PMID:196087", "title": "ATPase and phosphatase activities from human red cell membranes: II. The effects of phospholipases on Ca2+-dependent enzymic activities.", "content": "Treatment of human red cell membranes with pure phospholipase A2 results in a progressive inactivation of both Ca2+-dependent and (Ca2+ + K+)-dependent ATPase and phosphatase activities. When phospholipase C replaces phospholipase A2, Ca2+-dependent ATPase activity and Ca2+-dependent phosphorylation of red cell membranes are lost, while Ca2+-dependent phosphatase activity is enhanced and its apparent affinity for Ca2+ is increased about 20-fold. Activation of Ca2+-dependent phosphatase following phospholipase C treatment was not observed in sarcoplasmic reticulum preparation. Phospholipase C increases the sensitivity of the phosphatase to N-ethylmaleimide but has little effect on the kinetic parameters relating the phosphatase activity to substrate and cofactors, suggesting that no extensive structural disarrangement of the Ca2+-ATPase system has occurred after incubation with phospholipase C.", "contents": "ATPase and phosphatase activities from human red cell membranes: II. The effects of phospholipases on Ca2+-dependent enzymic activities. Treatment of human red cell membranes with pure phospholipase A2 results in a progressive inactivation of both Ca2+-dependent and (Ca2+ + K+)-dependent ATPase and phosphatase activities. When phospholipase C replaces phospholipase A2, Ca2+-dependent ATPase activity and Ca2+-dependent phosphorylation of red cell membranes are lost, while Ca2+-dependent phosphatase activity is enhanced and its apparent affinity for Ca2+ is increased about 20-fold. Activation of Ca2+-dependent phosphatase following phospholipase C treatment was not observed in sarcoplasmic reticulum preparation. Phospholipase C increases the sensitivity of the phosphatase to N-ethylmaleimide but has little effect on the kinetic parameters relating the phosphatase activity to substrate and cofactors, suggesting that no extensive structural disarrangement of the Ca2+-ATPase system has occurred after incubation with phospholipase C."}
{"id": "PMID:196089", "title": "Active chloride secretion by rabbit colon: calcium-dependent stimulation by ionophore A23187.", "content": "Addition of Ca ionophore, A23187, to the solution bathing the mucosal surface of descending rabbit colon resulted in a reversal of active C1absorption to active C1 secretion, a twofold increase in short-circuit current and a 40% increase in tissue conductance without affecting the rate of active Na absorption. These alterations in electrolyte transport are quantitatively similar to those previously observed in response to cyclic 3',5'-AMP (cAMP) (RA. Frizzell, M.J. Koch & S.G. Schulz, J. Membrane Biol. 27:297, 1976). When medium Ca concentration was reduced to 10(-6) M, the secretory response to A23187 was abolished but the response to cAMP was unaffected. The ionophore did not influence the cAMP levels of colonic mucosa. Addition of cyclic AMP to colonic strips preloaded with 45Ca elicited a reversible increase in Ca efflux from the tissue. These results suggest that an increase in intracellular Ca concentration stimulates colonic electrolyte secretion and that the secretory response to cAMP may be due, at least in part, to a release of Ca from intracellular stores.", "contents": "Active chloride secretion by rabbit colon: calcium-dependent stimulation by ionophore A23187. Addition of Ca ionophore, A23187, to the solution bathing the mucosal surface of descending rabbit colon resulted in a reversal of active C1absorption to active C1 secretion, a twofold increase in short-circuit current and a 40% increase in tissue conductance without affecting the rate of active Na absorption. These alterations in electrolyte transport are quantitatively similar to those previously observed in response to cyclic 3',5'-AMP (cAMP) (RA. Frizzell, M.J. Koch & S.G. Schulz, J. Membrane Biol. 27:297, 1976). When medium Ca concentration was reduced to 10(-6) M, the secretory response to A23187 was abolished but the response to cAMP was unaffected. The ionophore did not influence the cAMP levels of colonic mucosa. Addition of cyclic AMP to colonic strips preloaded with 45Ca elicited a reversible increase in Ca efflux from the tissue. These results suggest that an increase in intracellular Ca concentration stimulates colonic electrolyte secretion and that the secretory response to cAMP may be due, at least in part, to a release of Ca from intracellular stores."}
{"id": "PMID:196095", "title": "Biochemical studies of taste sensation: II. Labelling of cyclic AMP of bovine taste papillae in response to sweet and bitter stimuli.", "content": "Labeling of cyclic AMP of tase papillae and its responsiveness to tast stimuli has been measured using whole papillae from bovine tongue prelabeled with [ 8-(14) C] adenine. Labeling was measured in circumvallate and fungiform papillae, both of which contain taste buds, and in filiform papillae and small blocks of tongue epithelium, which are devoid of taste buds. No differences were observed in the levels of activity. The labeling of cyclic AMP of circumvallate papillae showed only small increases (12-22%) in the presence of the taste stimulus sucrose (sweet), and the stimulatory effects were not statistically significant. The increase due to sucrose was not potentiated by theophylline. No stimulation by sucrose was observed with epithelium controls. Lactose, which is a poor taste stimulus, did not stimulate labeling of cyclic AMP in taste papillae. Theophylline, caffeine, and quinine (bitter) stimulated labeling of cyclic AMP by up to 2-fold, as did L-Epinephrine. Evidence for a specific role of cyclic AMP as a second messenger in taste sensation was not obtained. It is suggested that cyclic AMP might provide a mechanistic basis for studying some of the effects of sweet and bitter compounds in mixtures.", "contents": "Biochemical studies of taste sensation: II. Labelling of cyclic AMP of bovine taste papillae in response to sweet and bitter stimuli. Labeling of cyclic AMP of tase papillae and its responsiveness to tast stimuli has been measured using whole papillae from bovine tongue prelabeled with [ 8-(14) C] adenine. Labeling was measured in circumvallate and fungiform papillae, both of which contain taste buds, and in filiform papillae and small blocks of tongue epithelium, which are devoid of taste buds. No differences were observed in the levels of activity. The labeling of cyclic AMP of circumvallate papillae showed only small increases (12-22%) in the presence of the taste stimulus sucrose (sweet), and the stimulatory effects were not statistically significant. The increase due to sucrose was not potentiated by theophylline. No stimulation by sucrose was observed with epithelium controls. Lactose, which is a poor taste stimulus, did not stimulate labeling of cyclic AMP in taste papillae. Theophylline, caffeine, and quinine (bitter) stimulated labeling of cyclic AMP by up to 2-fold, as did L-Epinephrine. Evidence for a specific role of cyclic AMP as a second messenger in taste sensation was not obtained. It is suggested that cyclic AMP might provide a mechanistic basis for studying some of the effects of sweet and bitter compounds in mixtures."}
{"id": "PMID:196096", "title": "Genetic studies of the Fv-1 locus of mice: linkage with Gpd-1 in recombinant inbred lines.", "content": "Multiple recombinant inbred lines, derived from crosses between strains permissive to N-tropic murine leukemia viruses (Fv-1n) and strains permissive to B-tropic murine leukemia viruses (Fv-1b), have been characterized as to Fv-1 genotype and other chromosome 4 markers, including the closely linked hexose-6-phosphate dehydrogenase isozyme locus (Gpd-1). Only one recombinant between Fv-1 and Gpd-1 was found among 45 lines tested. On this basis, the distance between Fv-1 and Gpd-1 is estimated to be 0.6 centimorgans. None of the lines was either resistant or susceptible to both N- and B-tropic viruses. Nineteen other inbred strains, previously untested, were characterized as either Fv-1n or Fv-1b.", "contents": "Genetic studies of the Fv-1 locus of mice: linkage with Gpd-1 in recombinant inbred lines. Multiple recombinant inbred lines, derived from crosses between strains permissive to N-tropic murine leukemia viruses (Fv-1n) and strains permissive to B-tropic murine leukemia viruses (Fv-1b), have been characterized as to Fv-1 genotype and other chromosome 4 markers, including the closely linked hexose-6-phosphate dehydrogenase isozyme locus (Gpd-1). Only one recombinant between Fv-1 and Gpd-1 was found among 45 lines tested. On this basis, the distance between Fv-1 and Gpd-1 is estimated to be 0.6 centimorgans. None of the lines was either resistant or susceptible to both N- and B-tropic viruses. Nineteen other inbred strains, previously untested, were characterized as either Fv-1n or Fv-1b."}
{"id": "PMID:196097", "title": "Physiological state of human embryonic lung cells affects their response to human cytomegalovirus.", "content": "Cultures of human embryonic lung (HEL) cells in different physiological states were studied for their susceptibility to infection with human cytomegalovirus (CMV) with respect to production of infectious virus, synthesis of viral antigens, and virus-induced stimulation of cellular DNA synthesis. In general, subconfluent, actively growing cells yielded higher amounts of infectious virus than did confluent contact-inhibited cells. The higher yield of infectious virus was correlated with a greater percentage of cells producing viral antigens within the first 48 h after infection. In confluent cultures, 25 to 50% of the cells produced viral antigens within the first 48 h postinfection. This proportion did not change over a 10-fold range of multiplicity of infection, indicating that many of the cells in confluent cultures did not support productive infection. However, virtually all the cells in subconfluent cultures were susceptible. Also, in contrast to herpes simplex virus and pseudorabies virus, infectious CMV is not produced by cells treated with 5-fluorouracil and thymidine. Virus-induced stimulation of cellular DNA synthesis in cells infected at high multiplicities of infection could be detected only in confluent cultures, in which cellular DNA synthesis had been previously suppressed, but could not be detected in similarly treated cultures of subconfluent cells. The lack of detectable stimulation of cellular DNA synthesis in the latter was related to the fact that practically all the cells in the culture synthesized viral antigens within the first 48 h after infection, productive infection and detectable synthesis of cellular DNA being mutually exclusive.", "contents": "Physiological state of human embryonic lung cells affects their response to human cytomegalovirus. Cultures of human embryonic lung (HEL) cells in different physiological states were studied for their susceptibility to infection with human cytomegalovirus (CMV) with respect to production of infectious virus, synthesis of viral antigens, and virus-induced stimulation of cellular DNA synthesis. In general, subconfluent, actively growing cells yielded higher amounts of infectious virus than did confluent contact-inhibited cells. The higher yield of infectious virus was correlated with a greater percentage of cells producing viral antigens within the first 48 h after infection. In confluent cultures, 25 to 50% of the cells produced viral antigens within the first 48 h postinfection. This proportion did not change over a 10-fold range of multiplicity of infection, indicating that many of the cells in confluent cultures did not support productive infection. However, virtually all the cells in subconfluent cultures were susceptible. Also, in contrast to herpes simplex virus and pseudorabies virus, infectious CMV is not produced by cells treated with 5-fluorouracil and thymidine. Virus-induced stimulation of cellular DNA synthesis in cells infected at high multiplicities of infection could be detected only in confluent cultures, in which cellular DNA synthesis had been previously suppressed, but could not be detected in similarly treated cultures of subconfluent cells. The lack of detectable stimulation of cellular DNA synthesis in the latter was related to the fact that practically all the cells in the culture synthesized viral antigens within the first 48 h after infection, productive infection and detectable synthesis of cellular DNA being mutually exclusive."}
{"id": "PMID:196098", "title": "Complementation rescue of Rous sarcoma virus from transformed mammalian cells by polyethylene glycol-mediated cell fusion.", "content": "Polyethylene glycol (PEG) is effective as a fusing agent for the rescue of virus from Rous sarcoma virus-transformed mammalian cells. The procedure of PEG-mediated rescue of virus from virogenic cell lines is described, and the technique is compared with that of Sendai virus-mediated rescue. Virus may be rescued quantitatively from virogenic cell lines by plating mitomycin C-killed transformed mammalian cells with chicken embryo cells, treating the monolayers with 50% PEG and overlaying the monolayers with focus agar. The number of foci that appeared reflected the number of heterokaryons in the fusion mixtures that released infectious virus. PEG gave reproducible results in virus rescue experiments with an efficiency equal to the best Sendai virus preparations. In addition to the description of the technique for PEG-mediated virus rescue from virogenic cell lines, a method for virus rescue from nonvirogenic lines is presented. Preinfection of the chicken embryo cells with helper avian leukosis virus (Rous-associated virus) prior to fusion with mammalian cells transformed by defective viruses complements the virus defect. We examined four nonvirogenic cell lines, and all released infectious virus in the complementation rescue assay.", "contents": "Complementation rescue of Rous sarcoma virus from transformed mammalian cells by polyethylene glycol-mediated cell fusion. Polyethylene glycol (PEG) is effective as a fusing agent for the rescue of virus from Rous sarcoma virus-transformed mammalian cells. The procedure of PEG-mediated rescue of virus from virogenic cell lines is described, and the technique is compared with that of Sendai virus-mediated rescue. Virus may be rescued quantitatively from virogenic cell lines by plating mitomycin C-killed transformed mammalian cells with chicken embryo cells, treating the monolayers with 50% PEG and overlaying the monolayers with focus agar. The number of foci that appeared reflected the number of heterokaryons in the fusion mixtures that released infectious virus. PEG gave reproducible results in virus rescue experiments with an efficiency equal to the best Sendai virus preparations. In addition to the description of the technique for PEG-mediated virus rescue from virogenic cell lines, a method for virus rescue from nonvirogenic lines is presented. Preinfection of the chicken embryo cells with helper avian leukosis virus (Rous-associated virus) prior to fusion with mammalian cells transformed by defective viruses complements the virus defect. We examined four nonvirogenic cell lines, and all released infectious virus in the complementation rescue assay."}
{"id": "PMID:196099", "title": "Oligonucleotide fingerprints of RNA species obtained from rhabdoviruses belonging to the vesicular stomatitis virus subgroup.", "content": "The relationships among the genomes of various rhabdoviruses belonging to the vesicular stomatitis virus subgroup were analyzed by an oligonucleotide fingerprinting technique. Of 10 vesicular stomatitis viruses, Indiana serotype (VSV Indiana), obtained from various sources, either no, few, or many differences were observed in the oligonucleotide fingerprints of the 42S RNA species extracted from standard B virions. Analyses of the oligonucleotides obtained from RNA extracted from three separate preparations of VSV Indiana defective T particles showed that their RNAs contain fewer oligonucleotides than the corresponding B particle RNA species. The fingerprints of RNA obtained from five VSV New Jersey serotype viruses were easily distinguished from those of the VSV Indiana isolates. Three of the VSV New Jersey RNA fingerprints were similar to each other but quite different from those of the other two viruses. The RNA fingerprints of two Chandipura virus isolates (one obtained from India and one from Nigeria) were also unique, whereas the fingerprint of Cocal virus RNA was unlike that of the serologically related VSV Indiana.", "contents": "Oligonucleotide fingerprints of RNA species obtained from rhabdoviruses belonging to the vesicular stomatitis virus subgroup. The relationships among the genomes of various rhabdoviruses belonging to the vesicular stomatitis virus subgroup were analyzed by an oligonucleotide fingerprinting technique. Of 10 vesicular stomatitis viruses, Indiana serotype (VSV Indiana), obtained from various sources, either no, few, or many differences were observed in the oligonucleotide fingerprints of the 42S RNA species extracted from standard B virions. Analyses of the oligonucleotides obtained from RNA extracted from three separate preparations of VSV Indiana defective T particles showed that their RNAs contain fewer oligonucleotides than the corresponding B particle RNA species. The fingerprints of RNA obtained from five VSV New Jersey serotype viruses were easily distinguished from those of the VSV Indiana isolates. Three of the VSV New Jersey RNA fingerprints were similar to each other but quite different from those of the other two viruses. The RNA fingerprints of two Chandipura virus isolates (one obtained from India and one from Nigeria) were also unique, whereas the fingerprint of Cocal virus RNA was unlike that of the serologically related VSV Indiana."}
{"id": "PMID:196100", "title": "Regulation of early and late simian virus 40 transcription: overproduction of early viral RNA in the absence of a functional T-antigen.", "content": "Virus-specific RNA synthesized in monkey cells after infection by both wild-type simian virus 40 (SV40) and the early SV40 temperature-sensitive mutant tsA58 has been analyzed. The fraction of SV40-specific RNA increased throughout infection with either wild-type SV40 or with tsA58 in direct proportion to the accumulation of progeny DNA molecules, suggesting their role in the late transcriptional process. Cytoplasmic fractions from cells infected at various temperatures (31.5 to 41 degrees C) by wild-type virus and harvested 48 h later contained 4 to 8% virus-specific RNA, of which 5 to 10% was early SV40 RNA. In contrast, though 5 to 8% of the cytoplasmic RNA from tsA 58-infected cells incubated at 31.5 to 37 degrees C for 48 h was virus specific, the percentage of early virus-specific RNA ranged from 25 to 80% as the incubation temperature increased. In tsA58-infected cultures incubated for 48 h at 41 degrees C (a temperature at which essentially no tsA 58 DNA synthesis occurred), only 0.4% of the cytoplasmic RNA was virus specific, but at least 90% of this RNA was early. In experiments where cells were inoculated at 32 degrees C and shifted at 48 h postinfection to 40 degrees C for various times, the percentage of virus-specific pulse-labeled RNA varied from 3.5 to 10.0%. Of the virus-specific RNA, early SV40 RNA ranged from 14 to 65% in tsA 58-infected cultures. Analogous studies with Sarkosyl-extracted viral transcription complexes to incorporate label into nascent (unprocessed) viral RNA yielded essentially identical results. This finding strongly suggests that the overproduction of early SV40 RNA occurs at the level of synthesis. While cytosine arabinoside effectively terminated most viral DNA replication in wild-type-infected cells, the ratio of early to late viral RNA remained less than 1:9. These results demonstrate that: (1) the amount of virus-specific RNA synthesized depends directly on the amount of viral DNA available for use as templates; once viral DNA replication has occurred, presumably providing progeny SV40 DNA molecules for templates, the level of transcription remains high; (ii) termination of viral DNA replication does not terminate late SV40 transcription; (iii) early SV40 RNA is overproduced by tsA 58 at all temperatures, but especially at higher temperatures; and (iv) overproduction of early SV40 RNA appears to be correlated with defectiveness of the tsA mutant T-antigen. These results suggest that T-antigen may regulate its own production either by repressing the synthesis of early viral RNA or by stimulating the synthesis of late SV40 RNA or both.", "contents": "Regulation of early and late simian virus 40 transcription: overproduction of early viral RNA in the absence of a functional T-antigen. Virus-specific RNA synthesized in monkey cells after infection by both wild-type simian virus 40 (SV40) and the early SV40 temperature-sensitive mutant tsA58 has been analyzed. The fraction of SV40-specific RNA increased throughout infection with either wild-type SV40 or with tsA58 in direct proportion to the accumulation of progeny DNA molecules, suggesting their role in the late transcriptional process. Cytoplasmic fractions from cells infected at various temperatures (31.5 to 41 degrees C) by wild-type virus and harvested 48 h later contained 4 to 8% virus-specific RNA, of which 5 to 10% was early SV40 RNA. In contrast, though 5 to 8% of the cytoplasmic RNA from tsA 58-infected cells incubated at 31.5 to 37 degrees C for 48 h was virus specific, the percentage of early virus-specific RNA ranged from 25 to 80% as the incubation temperature increased. In tsA58-infected cultures incubated for 48 h at 41 degrees C (a temperature at which essentially no tsA 58 DNA synthesis occurred), only 0.4% of the cytoplasmic RNA was virus specific, but at least 90% of this RNA was early. In experiments where cells were inoculated at 32 degrees C and shifted at 48 h postinfection to 40 degrees C for various times, the percentage of virus-specific pulse-labeled RNA varied from 3.5 to 10.0%. Of the virus-specific RNA, early SV40 RNA ranged from 14 to 65% in tsA 58-infected cultures. Analogous studies with Sarkosyl-extracted viral transcription complexes to incorporate label into nascent (unprocessed) viral RNA yielded essentially identical results. This finding strongly suggests that the overproduction of early SV40 RNA occurs at the level of synthesis. While cytosine arabinoside effectively terminated most viral DNA replication in wild-type-infected cells, the ratio of early to late viral RNA remained less than 1:9. These results demonstrate that: (1) the amount of virus-specific RNA synthesized depends directly on the amount of viral DNA available for use as templates; once viral DNA replication has occurred, presumably providing progeny SV40 DNA molecules for templates, the level of transcription remains high; (ii) termination of viral DNA replication does not terminate late SV40 transcription; (iii) early SV40 RNA is overproduced by tsA 58 at all temperatures, but especially at higher temperatures; and (iv) overproduction of early SV40 RNA appears to be correlated with defectiveness of the tsA mutant T-antigen. These results suggest that T-antigen may regulate its own production either by repressing the synthesis of early viral RNA or by stimulating the synthesis of late SV40 RNA or both."}
{"id": "PMID:196101", "title": "Polypeptide synthesis in simian virus 5-infected cells.", "content": "Polypeptide synthesis in three different cell types infected with simian virus 5 has been examined using high-resolution polyacrylamide slab gel electrophoresis, and all of the known viral polypeptides have been identified above the host cell background. The polypeptides were synthesized in infected cells in unequal proportions, which are approximately the same as they are found in virions, suggesting that their relative rates of synthesis are controlled. The nucleocapsid polypeptide (NP) was the first to be detected in infected cells, and by 12 to 14 h the other virion structural polypeptides were identified, except for the polypeptides comprising the smaller glycoprotein (F). However, a glycosylated precursor (F(0)) with a molecular weight of 66,000 was found in each cell type, and pulse-chase experiments suggested that this precursor was cleaved to yield polypeptides F(1) and F(2). No other proteolytic processing was found. In addition to the structural polypeptides, the synthesis of five other polypeptides, designated I through V, has been observed in simian virus 5-infected cells. One of these (V), with a molecular weight of 24,000, was found in all cells examined and may be a nonstructural viral polypeptide. In contrast, there are polypeptides present in uninfected cells that correspond in size to polypeptides I through IV, and similar polypeptides have also been detected in increased amounts in cells infected with Sendai virus. These findings, and the fact that the synthesis of all four of these polypeptides is not increased in every cell type, suggest that they represent host polypeptides whose synthesis may be enhanced upon infection. When a high salt concentration was used to decrease host cell protein synthesis in infected cells, polypeptides IV and (to a lesser extent) I were synthesized in relatively greater amounts than other cellular polypeptides, as were the viral polypeptides. The possibility that these polypeptides may play some role in virus replication is discussed.", "contents": "Polypeptide synthesis in simian virus 5-infected cells. Polypeptide synthesis in three different cell types infected with simian virus 5 has been examined using high-resolution polyacrylamide slab gel electrophoresis, and all of the known viral polypeptides have been identified above the host cell background. The polypeptides were synthesized in infected cells in unequal proportions, which are approximately the same as they are found in virions, suggesting that their relative rates of synthesis are controlled. The nucleocapsid polypeptide (NP) was the first to be detected in infected cells, and by 12 to 14 h the other virion structural polypeptides were identified, except for the polypeptides comprising the smaller glycoprotein (F). However, a glycosylated precursor (F(0)) with a molecular weight of 66,000 was found in each cell type, and pulse-chase experiments suggested that this precursor was cleaved to yield polypeptides F(1) and F(2). No other proteolytic processing was found. In addition to the structural polypeptides, the synthesis of five other polypeptides, designated I through V, has been observed in simian virus 5-infected cells. One of these (V), with a molecular weight of 24,000, was found in all cells examined and may be a nonstructural viral polypeptide. In contrast, there are polypeptides present in uninfected cells that correspond in size to polypeptides I through IV, and similar polypeptides have also been detected in increased amounts in cells infected with Sendai virus. These findings, and the fact that the synthesis of all four of these polypeptides is not increased in every cell type, suggest that they represent host polypeptides whose synthesis may be enhanced upon infection. When a high salt concentration was used to decrease host cell protein synthesis in infected cells, polypeptides IV and (to a lesser extent) I were synthesized in relatively greater amounts than other cellular polypeptides, as were the viral polypeptides. The possibility that these polypeptides may play some role in virus replication is discussed."}
{"id": "PMID:196102", "title": "RNase T1-resistant oligonucleotides of B-tropic murine leukemia virus from BALB/c and five of its NB-tropic derivatives.", "content": "We used two-dimensional gel electrophoresis to obtain fingerprints of RNase T1-resistant oligonucleotides of a B-tropic murine leukemia virus from BALB/c and five NB-tropic viruses independently derived from this B virus by passage through NIH Swiss mouse embryo cells in vitro. The fingerprints of the B- and NB-tropic viruses were very similar: approximately 33 of 35 large T1-resistant oligonucleotides appeared to be shared by these viruses. However, the five NB-tropic viruses possessed an apparently common alteration relative to their B virus progenitor. This change involved the acquisition of one oligonucleotide and, tentatively, the loss of one oligonucleotide. We do not know whether these changes represent an alteration responsible for the change from B- to NB-tropism. Fingerprints of B- and NB-tropic viruses were not affected when the viruses were grown in cells of different Fv-1 type.", "contents": "RNase T1-resistant oligonucleotides of B-tropic murine leukemia virus from BALB/c and five of its NB-tropic derivatives. We used two-dimensional gel electrophoresis to obtain fingerprints of RNase T1-resistant oligonucleotides of a B-tropic murine leukemia virus from BALB/c and five NB-tropic viruses independently derived from this B virus by passage through NIH Swiss mouse embryo cells in vitro. The fingerprints of the B- and NB-tropic viruses were very similar: approximately 33 of 35 large T1-resistant oligonucleotides appeared to be shared by these viruses. However, the five NB-tropic viruses possessed an apparently common alteration relative to their B virus progenitor. This change involved the acquisition of one oligonucleotide and, tentatively, the loss of one oligonucleotide. We do not know whether these changes represent an alteration responsible for the change from B- to NB-tropism. Fingerprints of B- and NB-tropic viruses were not affected when the viruses were grown in cells of different Fv-1 type."}
{"id": "PMID:196103", "title": "Properties of simian virus 40 transcriptional intermediates isolated from nuclei of permissive cells.", "content": "A nucleoprotein complex that is an intermediate in viral transcription has been isolated from simian virus 40 (SV40)-infected BSC-1 cells after lysing infected nuclei with Sarkosyl. It contain DNA, DNA-dependent RNA polymerase II, and nascent RNA chains. RNA chain elongation continues for several hours in vitro and is dependent on exogenous ribonucleoside triphosphates. The complex sediments in neutral sucrose gradients with a main peak at about 24 to 26S. When the nascent RNA on the complex is treated with RNase A, a fraction of the RNA remains resistant to RNase and is hydrogen bonded to the DNA template. The pulse-labeled RNase-resistant RNA can be chased into RNase-sensitive RNA, indicating that it is located at the 3' terminus of the RNA chain. The rate of RNA displacement from the DNA template is consistent with an average rate of RNA chain elongation of 15 to 30 nucleotides per min. At least 70% of the RNA synthesized in this in vitro system is SV40 specific. Hybridization with the separated strands of SV40 DNA and with fragments of SV40 DNA generated with endonucleases HindII + III indicates that this RNA  is complementary to all regions of the \"late\" SV40 DNA strand. Studies of SV40 RNA synthesis in this partially purified preparation at early and late times after infection should provide a way of locating promoter sites for transcription and identifying the form of SV40 DNA that serves as a template for late transcription.", "contents": "Properties of simian virus 40 transcriptional intermediates isolated from nuclei of permissive cells. A nucleoprotein complex that is an intermediate in viral transcription has been isolated from simian virus 40 (SV40)-infected BSC-1 cells after lysing infected nuclei with Sarkosyl. It contain DNA, DNA-dependent RNA polymerase II, and nascent RNA chains. RNA chain elongation continues for several hours in vitro and is dependent on exogenous ribonucleoside triphosphates. The complex sediments in neutral sucrose gradients with a main peak at about 24 to 26S. When the nascent RNA on the complex is treated with RNase A, a fraction of the RNA remains resistant to RNase and is hydrogen bonded to the DNA template. The pulse-labeled RNase-resistant RNA can be chased into RNase-sensitive RNA, indicating that it is located at the 3' terminus of the RNA chain. The rate of RNA displacement from the DNA template is consistent with an average rate of RNA chain elongation of 15 to 30 nucleotides per min. At least 70% of the RNA synthesized in this in vitro system is SV40 specific. Hybridization with the separated strands of SV40 DNA and with fragments of SV40 DNA generated with endonucleases HindII + III indicates that this RNA  is complementary to all regions of the \"late\" SV40 DNA strand. Studies of SV40 RNA synthesis in this partially purified preparation at early and late times after infection should provide a way of locating promoter sites for transcription and identifying the form of SV40 DNA that serves as a template for late transcription."}
{"id": "PMID:196104", "title": "Uniform representation of the human papovavirus BK genome in transformed hamster cells.", "content": "The DNA of three cloned lines of hamster kidney cells transformed by human papovavirus BK DNA was examined by reassociation kinetics for viral sequences and found to contain 2.7 to 5.3 equivalents of viral DNA per diploid genome. In the one line examined with the four R-HindIII fragments of the human papovavirus BK genome, the entire viral genome was uniformly represented.", "contents": "Uniform representation of the human papovavirus BK genome in transformed hamster cells. The DNA of three cloned lines of hamster kidney cells transformed by human papovavirus BK DNA was examined by reassociation kinetics for viral sequences and found to contain 2.7 to 5.3 equivalents of viral DNA per diploid genome. In the one line examined with the four R-HindIII fragments of the human papovavirus BK genome, the entire viral genome was uniformly represented."}
{"id": "PMID:196105", "title": "Ammonium chloride inhibits cell fusion induced by syn mutants of herpes simplex virus type 1.", "content": "Cell fusion induced by syn mutants of herpes simplex virus type 1 is inhibited by NH4Cl. The inhibition of fusion is both rapid and rapidly reversible and apprears to be due to the NH4+ ion. Virus production was not significantly altered by NH4Cl, although cell growth was greatly diminished.", "contents": "Ammonium chloride inhibits cell fusion induced by syn mutants of herpes simplex virus type 1. Cell fusion induced by syn mutants of herpes simplex virus type 1 is inhibited by NH4Cl. The inhibition of fusion is both rapid and rapidly reversible and apprears to be due to the NH4+ ion. Virus production was not significantly altered by NH4Cl, although cell growth was greatly diminished."}
{"id": "PMID:196106", "title": "Type C viral gag gene expression in chicken embryo fibroblasts and avian sarcoma virus-transformed mammalian cells.", "content": "Sensitive radioimmunoassays were developed for avian type C viral gag gene-coded proteins. These assays were used to examine the restriction to virus production by avian embryo cells and mammalian cells transformed by avian sarcoma viruses. The results indicate that although a high-molecular-weight primary translational product of the gag gene is expressed, its cleavage and processing are incomplete. Furthermore, analysis of intermediate cleavage products provided information regarding the order of sequences coding for the individual viral proteins within the avian type C viral gag gene.", "contents": "Type C viral gag gene expression in chicken embryo fibroblasts and avian sarcoma virus-transformed mammalian cells. Sensitive radioimmunoassays were developed for avian type C viral gag gene-coded proteins. These assays were used to examine the restriction to virus production by avian embryo cells and mammalian cells transformed by avian sarcoma viruses. The results indicate that although a high-molecular-weight primary translational product of the gag gene is expressed, its cleavage and processing are incomplete. Furthermore, analysis of intermediate cleavage products provided information regarding the order of sequences coding for the individual viral proteins within the avian type C viral gag gene."}
{"id": "PMID:196107", "title": "Sizes and concentrations of several type C oncornaviruses and bacteriophage T2 by the resistive-pulse technique.", "content": "Viruses above about 60 nm in diameter may be rapidly sized to a few nanometers in their natural hydrated state as they pass one by one through a single pore in a newly developed nanometer-particle analyzer based on the resistive-pulse technique of the Coulter Counter and the use of submicron diameter pores made by the Nuclepore process. Size measurements for several type C oncornaviruses are: Rauscher murine leukemia, 122.3 +/- 2 nm; simian sarcoma, 109.7 +/- 3 nm; Mason-Pfizer monkey, 140.0 +/- 2.5 nm; RD-114, 115 +/- 5 nm; and feline leukemia, 127.4 +/- 2 nm, relative to standard 109-nm latex spheres. The T2 bacteriophage has a volume of (5.10 +/- 0.15) X 10(-16) cm3. Concentrations of viruses near 10(9) to 10(11)/ml that are fairly clear of debris are routinely measurable in a few minutes to an accuracy near 15%. A lower practical count limit is near 5 X 10(7) viruses per ml.", "contents": "Sizes and concentrations of several type C oncornaviruses and bacteriophage T2 by the resistive-pulse technique. Viruses above about 60 nm in diameter may be rapidly sized to a few nanometers in their natural hydrated state as they pass one by one through a single pore in a newly developed nanometer-particle analyzer based on the resistive-pulse technique of the Coulter Counter and the use of submicron diameter pores made by the Nuclepore process. Size measurements for several type C oncornaviruses are: Rauscher murine leukemia, 122.3 +/- 2 nm; simian sarcoma, 109.7 +/- 3 nm; Mason-Pfizer monkey, 140.0 +/- 2.5 nm; RD-114, 115 +/- 5 nm; and feline leukemia, 127.4 +/- 2 nm, relative to standard 109-nm latex spheres. The T2 bacteriophage has a volume of (5.10 +/- 0.15) X 10(-16) cm3. Concentrations of viruses near 10(9) to 10(11)/ml that are fairly clear of debris are routinely measurable in a few minutes to an accuracy near 15%. A lower practical count limit is near 5 X 10(7) viruses per ml."}
{"id": "PMID:196108", "title": "5'-Terminal and internal methylated nucleosides in herpes simplex virus type 1 mRNA.", "content": "RNA labeled with [methyl-3H]methionine and/or [32P]orthophosphate was isolated from the polyribosomes of herpes simplex virus (HSV) types 1-infected cells and separated into polyadenylylated [poly(A+)]and non-polyadenylylated [poly(A-)] fractions. Virus-specific RNA was obtained by hybridization in liquid to either excess HSV DNA or filters containing immobilized HSV DNA. Analysis in denaturing sucrose gradients indicated that HSV-specific poly(A+) RNA sedimented in a broad peak, with a modal S value of 20. The ratio of [3H]methyl to 32P decreased with increasing size of RNA, suggesting that each RNA chain contains a similar sumber of methyl groups. Further analysis indicated an average of one RNase-resistant structure of the type m7G(5')pppNmpNp or m7G(5')pppNmpNmpNp per 2,780 nucleotides. The following components were identified in the 5'-terminal oligonucleotides of polyribosome-associated HSV-specific poly(A+) and poly(A-) RNA: 7-methylguanosine, N6,2'-O-dimethyladenosine, and the 2'-O-methyl derivatives of guanosine, adenosine, uridine, and denosine, and the 2'-O-methyl derivatives of guanosine, adenosine, uridine, and cytidine. The most common 5'-terminal sequences were m7G(5')pppm6Am and m7G(5')pppGm. An additional modified nucleoside, N6-methyladenosine, was present in an internal position of HSV-specific RNA.", "contents": "5'-Terminal and internal methylated nucleosides in herpes simplex virus type 1 mRNA. RNA labeled with [methyl-3H]methionine and/or [32P]orthophosphate was isolated from the polyribosomes of herpes simplex virus (HSV) types 1-infected cells and separated into polyadenylylated [poly(A+)]and non-polyadenylylated [poly(A-)] fractions. Virus-specific RNA was obtained by hybridization in liquid to either excess HSV DNA or filters containing immobilized HSV DNA. Analysis in denaturing sucrose gradients indicated that HSV-specific poly(A+) RNA sedimented in a broad peak, with a modal S value of 20. The ratio of [3H]methyl to 32P decreased with increasing size of RNA, suggesting that each RNA chain contains a similar sumber of methyl groups. Further analysis indicated an average of one RNase-resistant structure of the type m7G(5')pppNmpNp or m7G(5')pppNmpNmpNp per 2,780 nucleotides. The following components were identified in the 5'-terminal oligonucleotides of polyribosome-associated HSV-specific poly(A+) and poly(A-) RNA: 7-methylguanosine, N6,2'-O-dimethyladenosine, and the 2'-O-methyl derivatives of guanosine, adenosine, uridine, and denosine, and the 2'-O-methyl derivatives of guanosine, adenosine, uridine, and cytidine. The most common 5'-terminal sequences were m7G(5')pppm6Am and m7G(5')pppGm. An additional modified nucleoside, N6-methyladenosine, was present in an internal position of HSV-specific RNA."}
{"id": "PMID:196109", "title": "Interaction of polyoma and mouse DNAs. IV. Time course and extent of integration of polyoma DNA into mouse DNA during lytic infection.", "content": "The time course of covalent binding of polyoma viral DNA to mouse DNA was followed in mouse embryo cells that had been grown prior to infection in the presence of 5-bromodeoxyuridine. Density-labeled (HL) mouse DNA was separated from free polyoma DNA by CsCl isopycnic centrifugation. Polyoma DNA sequences present in HL mouse DNA were detected by hybridization with radioactive cRNA synthesized in vitro. In reconstruction experiments, the limit of detection was found to be, on the average, about 0.5 genome equivalent (g.e.) of polyoma DNA per cell. To find conditions for the isolation of HL mouse DNA and for its complete separation from free polyoma DNA, cultures infected at 4 degrees C were used. HL mouse DNA extracted with sodium dodecyl sulfate and high salt concentrations (5 to 6 M CsCl) and then purified by three consecutive CsCl density gradient centrifugations was free from detectable amounts of polyoma DNA, whereas HL mouse DNA extracted with chloroform and phenol and purified in the same way always contained contaminating, noncovalently bound polyoma DNA. In lytically infected bromodeoxyuridine-prelabeled mouse embryo cultures, polyoma DNA bound to HL mouse DNA that had been extracted by the sodium dodecyl sulfate-CsCl procedure was first detected in small amounts (1 to 2 g.e. per cell) at 10 h after infection. In cultures incubated with medium containing thymidine (5 mug/ml), 4 to 6 g.e. of polyoma DNA per cell was detected at 14 and 18 h after infection. In these samples, practically all viral DNA was bound to high-molecular-weight HL mouse DNA. In cultures incubated with normal medium (no additions) and extracted between 17 and 20 h after infection, 20 to 350 g.e. of polyoma DNA per cell banded with HL mouse DNA. However, when DNA of one of these samples was subfractionated by sodium dodecyl sulfate-salt precipitation prior to isolation of HL mouse DNA, about 80% of the viral DNA banding at increased density was present in the low-molecular-weight DNA fraction. This observation suggests that in normal medium some progeny viral DNA of increased density was synthesized. Covalent binding of polyoma DNA to density-labeled mouse DNA was demonstrated by alkaline CsCl density gradient centrifugation: nearly equal amounts of polyoma DNA were found in the H and L strands, respectively, as is expected for linear integration of viral DNA. The results lead to the conclusions that (i) early polyoma mRNA is transcribed from free parental viral DNA; (ii) covalent linear integration is first detectable at the time when tumor (T)-antigen is synthesized; and (iii) only few copies (<10 g.e./cell) become integrated between 10 and 18 h after infection, i.e., during the period when cellular and viral DNA replication starts in individual cells.", "contents": "Interaction of polyoma and mouse DNAs. IV. Time course and extent of integration of polyoma DNA into mouse DNA during lytic infection. The time course of covalent binding of polyoma viral DNA to mouse DNA was followed in mouse embryo cells that had been grown prior to infection in the presence of 5-bromodeoxyuridine. Density-labeled (HL) mouse DNA was separated from free polyoma DNA by CsCl isopycnic centrifugation. Polyoma DNA sequences present in HL mouse DNA were detected by hybridization with radioactive cRNA synthesized in vitro. In reconstruction experiments, the limit of detection was found to be, on the average, about 0.5 genome equivalent (g.e.) of polyoma DNA per cell. To find conditions for the isolation of HL mouse DNA and for its complete separation from free polyoma DNA, cultures infected at 4 degrees C were used. HL mouse DNA extracted with sodium dodecyl sulfate and high salt concentrations (5 to 6 M CsCl) and then purified by three consecutive CsCl density gradient centrifugations was free from detectable amounts of polyoma DNA, whereas HL mouse DNA extracted with chloroform and phenol and purified in the same way always contained contaminating, noncovalently bound polyoma DNA. In lytically infected bromodeoxyuridine-prelabeled mouse embryo cultures, polyoma DNA bound to HL mouse DNA that had been extracted by the sodium dodecyl sulfate-CsCl procedure was first detected in small amounts (1 to 2 g.e. per cell) at 10 h after infection. In cultures incubated with medium containing thymidine (5 mug/ml), 4 to 6 g.e. of polyoma DNA per cell was detected at 14 and 18 h after infection. In these samples, practically all viral DNA was bound to high-molecular-weight HL mouse DNA. In cultures incubated with normal medium (no additions) and extracted between 17 and 20 h after infection, 20 to 350 g.e. of polyoma DNA per cell banded with HL mouse DNA. However, when DNA of one of these samples was subfractionated by sodium dodecyl sulfate-salt precipitation prior to isolation of HL mouse DNA, about 80% of the viral DNA banding at increased density was present in the low-molecular-weight DNA fraction. This observation suggests that in normal medium some progeny viral DNA of increased density was synthesized. Covalent binding of polyoma DNA to density-labeled mouse DNA was demonstrated by alkaline CsCl density gradient centrifugation: nearly equal amounts of polyoma DNA were found in the H and L strands, respectively, as is expected for linear integration of viral DNA. The results lead to the conclusions that (i) early polyoma mRNA is transcribed from free parental viral DNA; (ii) covalent linear integration is first detectable at the time when tumor (T)-antigen is synthesized; and (iii) only few copies (<10 g.e./cell) become integrated between 10 and 18 h after infection, i.e., during the period when cellular and viral DNA replication starts in individual cells."}
{"id": "PMID:196110", "title": "Addition of extra DNA sequences to simian virus 40 DNA in vivo.", "content": "The possible addition of extra sequences to simian virus 40 (SV40) DNA was analyzed by electron microscopy in two different cell systems, productively infected monkey cells and activated heterokaryons on monkey and transformed mouse 3T3 cells. We found that the closed circular DNA fraction, extracted from monkey cells at 70 h after infection with nondefective SV40 at a multiplicity of infection of 6 PFU/cell, contained oversized molesules (1.1 to 2.0 fractional lengths of SV40 DNA) constituting about 8% of the molecules having lengths equal to or shorter than SV40 dinner DNA. The oversized molecules had the entired SV40 sequences. The added DNA was heterogeneous in length. The sites of addition were not specific with reference to the EcoRi site. These results suggest that recombination between monkey and SV40 DNAs or partial duplication of SV40 DNA occurs at many sites on the SV40 chromosome. The integrated SV40 DNA is excised and replicates in activated heterokaryons. In this system, besides SV40 DNA we found heterogeneous undersized and oversized molecules containing SV40 sequences in the closed circular DNA population. Additions differeing in size appeared to be overlapping and to have occurred at a preferential site on the SV40 chromosome. These results support the hypothesis that host DNA can be added to SV40 DNA at the site of integration at the time of excision.", "contents": "Addition of extra DNA sequences to simian virus 40 DNA in vivo. The possible addition of extra sequences to simian virus 40 (SV40) DNA was analyzed by electron microscopy in two different cell systems, productively infected monkey cells and activated heterokaryons on monkey and transformed mouse 3T3 cells. We found that the closed circular DNA fraction, extracted from monkey cells at 70 h after infection with nondefective SV40 at a multiplicity of infection of 6 PFU/cell, contained oversized molesules (1.1 to 2.0 fractional lengths of SV40 DNA) constituting about 8% of the molecules having lengths equal to or shorter than SV40 dinner DNA. The oversized molecules had the entired SV40 sequences. The added DNA was heterogeneous in length. The sites of addition were not specific with reference to the EcoRi site. These results suggest that recombination between monkey and SV40 DNAs or partial duplication of SV40 DNA occurs at many sites on the SV40 chromosome. The integrated SV40 DNA is excised and replicates in activated heterokaryons. In this system, besides SV40 DNA we found heterogeneous undersized and oversized molecules containing SV40 sequences in the closed circular DNA population. Additions differeing in size appeared to be overlapping and to have occurred at a preferential site on the SV40 chromosome. These results support the hypothesis that host DNA can be added to SV40 DNA at the site of integration at the time of excision."}
{"id": "PMID:196111", "title": "Encephalomyocarditis virus RNA. II. Polyadenylic acid requirement for efficient translation.", "content": "Differentially polyadenylated subpopulatons of encephalomyocarditis (EMC) viral RNA were isolated by affinity chromatography on oligodeoxythymidylic acid-cellulose. Translation of these RNA fractions in several in vitro protein-synthesizing systems, isolated from Ehrlich ascites tumor cells, demonstrated that poly(A)+EMC viral RNA was translated two to three times more efficiently than poly(A)-EMC viral RNA. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of the polypetides synthesized by the in vitro system in response to the different RNAs showed no detectable differences in the size or relative amount- of the translational products. mRNA saturation curves indicated that the in vitro systems were stimulated maximally by equivalent amounts of RNA, wheter it be poly(A)-or poly(A)+ EMC viral RNA. Time course experiments showed that the differences in translatability were more pronounced late in the reaction when reinitiation was required, and that by eliminating reinitiation with high salt the apparent effect of poly(A) on translation was diminished. Together, these results suggest that poly(A) may be required for efficient initiation and reinitiation of protein synthesis in the cell-free systems. This interpretation is discussed relative to earlier data.", "contents": "Encephalomyocarditis virus RNA. II. Polyadenylic acid requirement for efficient translation. Differentially polyadenylated subpopulatons of encephalomyocarditis (EMC) viral RNA were isolated by affinity chromatography on oligodeoxythymidylic acid-cellulose. Translation of these RNA fractions in several in vitro protein-synthesizing systems, isolated from Ehrlich ascites tumor cells, demonstrated that poly(A)+EMC viral RNA was translated two to three times more efficiently than poly(A)-EMC viral RNA. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of the polypetides synthesized by the in vitro system in response to the different RNAs showed no detectable differences in the size or relative amount- of the translational products. mRNA saturation curves indicated that the in vitro systems were stimulated maximally by equivalent amounts of RNA, wheter it be poly(A)-or poly(A)+ EMC viral RNA. Time course experiments showed that the differences in translatability were more pronounced late in the reaction when reinitiation was required, and that by eliminating reinitiation with high salt the apparent effect of poly(A) on translation was diminished. Together, these results suggest that poly(A) may be required for efficient initiation and reinitiation of protein synthesis in the cell-free systems. This interpretation is discussed relative to earlier data."}
{"id": "PMID:196112", "title": "Heteroduplex study of the sequence relations between RD-114 and baboon viral RNAs.", "content": "The regions of sequence homology and nonhomology between the RNA genomes of RD-114 and baboon endogenous type C viruses have been mapped by an electron microscope heteroduplex study. Short complementary DNA (cDNA) copies (approximately 150 to 200 nucleotides in length) of RD-114 RNA were prepared by an endogenous synthesis; labels of polydeoxythymidylic acid [poly(dT)] were attached to the 3' ends of the cDNA molecules by a reaction catalyzed by deoxynucleotidyl terminal transferase. The cDNA-poly(dT) was hybridized to RD-114 RNA and to baboon viral RNA dimer (50 to 70S) units, and the position- of the poly(dT) labels were observed by electron microscopy. With RD-114, labels were distributed uniformly along the genome. With baboon virus RNA (monomer length, 9.5 kilobases [kb]), the regions of high homology with RD-114 cDNA were observed to lie in the intervals from 1.5 to 2.5 kb and from 3.7 to 5.5 kb from the 5' end. The relations of these heteroduplex maps to the known antigenic similarities and differences among the several viral proteins and to the genetic maps of the viruses are discussed.", "contents": "Heteroduplex study of the sequence relations between RD-114 and baboon viral RNAs. The regions of sequence homology and nonhomology between the RNA genomes of RD-114 and baboon endogenous type C viruses have been mapped by an electron microscope heteroduplex study. Short complementary DNA (cDNA) copies (approximately 150 to 200 nucleotides in length) of RD-114 RNA were prepared by an endogenous synthesis; labels of polydeoxythymidylic acid [poly(dT)] were attached to the 3' ends of the cDNA molecules by a reaction catalyzed by deoxynucleotidyl terminal transferase. The cDNA-poly(dT) was hybridized to RD-114 RNA and to baboon viral RNA dimer (50 to 70S) units, and the position- of the poly(dT) labels were observed by electron microscopy. With RD-114, labels were distributed uniformly along the genome. With baboon virus RNA (monomer length, 9.5 kilobases [kb]), the regions of high homology with RD-114 cDNA were observed to lie in the intervals from 1.5 to 2.5 kb and from 3.7 to 5.5 kb from the 5' end. The relations of these heteroduplex maps to the known antigenic similarities and differences among the several viral proteins and to the genetic maps of the viruses are discussed."}
{"id": "PMID:196113", "title": "Characterization of the protein and nucleic acid of Aleutian disease virus.", "content": "Aleutian disease virus (ADV) was extracted and purified from infected mink. Nucleic acid extracted from the virus was examined in an electron microscope. Three different sizes of molecule, with approximate lengths of 1.2, 0.55, and 0.25 micron, were observed. The ratios of the large molecules to the small molecules were similar in all the particles prepared under different conditions. Equilibrium CsCl density gradient centrifugation showed that ADV nucleic acid had a buoyant density of 1.733 g/cm3. In Cs2SO4, ADV had a lower buoyant density than that of double-stranded RNA. These properties and its sensitivity to DNase suggested that ADV contains DNA. Thermal denaturation curves revealed that the DNA of ADV had a single-stranded configuration. Polypeptide analysis of ADV by polyacrylamide gel electrophoresis revealed the presence of four polypepties, with molecular weights of 30,000, 27,000, 20,500, and 14,000. These polypeptides were present in a ratio of 10:3:10:1, respectively. The data suggested that ADV is closely related to the members of the parvovirus groups.", "contents": "Characterization of the protein and nucleic acid of Aleutian disease virus. Aleutian disease virus (ADV) was extracted and purified from infected mink. Nucleic acid extracted from the virus was examined in an electron microscope. Three different sizes of molecule, with approximate lengths of 1.2, 0.55, and 0.25 micron, were observed. The ratios of the large molecules to the small molecules were similar in all the particles prepared under different conditions. Equilibrium CsCl density gradient centrifugation showed that ADV nucleic acid had a buoyant density of 1.733 g/cm3. In Cs2SO4, ADV had a lower buoyant density than that of double-stranded RNA. These properties and its sensitivity to DNase suggested that ADV contains DNA. Thermal denaturation curves revealed that the DNA of ADV had a single-stranded configuration. Polypeptide analysis of ADV by polyacrylamide gel electrophoresis revealed the presence of four polypepties, with molecular weights of 30,000, 27,000, 20,500, and 14,000. These polypeptides were present in a ratio of 10:3:10:1, respectively. The data suggested that ADV is closely related to the members of the parvovirus groups."}
{"id": "PMID:196114", "title": "Morphogenesis of poliovirus. IV. existence of particles sedimenting at 150S and having the properties of provirion.", "content": "An apparent precursor to the poliovirion that cosediments with the virion at 150S was identified by its content of VP-0. It has properties previously associated with the provirion, a structure that sedimented at 125S, and it may be an alternate form of provirion. Like virions, the 150S precursor binds to and elutes from cells, after which it sediments at about 125S.", "contents": "Morphogenesis of poliovirus. IV. existence of particles sedimenting at 150S and having the properties of provirion. An apparent precursor to the poliovirion that cosediments with the virion at 150S was identified by its content of VP-0. It has properties previously associated with the provirion, a structure that sedimented at 125S, and it may be an alternate form of provirion. Like virions, the 150S precursor binds to and elutes from cells, after which it sediments at about 125S."}
{"id": "PMID:196115", "title": "Anatomy of herpes simplex virus DNA VIII. Properties of the replicating DNA.", "content": "This paper concerns the properties of herpes simplex virus 1 DNA replicating in HEp-2 and human embryonic lung cells. The results were as follows. (i) Only a small fraction of input viral DNA entered the replicative pool. The bulk of the input viral DNA cosedimented with marker viral DNA and did not appear to be degraded or dissociated into L and S components. (ii) Nascent DNA sedimented faster and banded at a higher density than that of mature viral DNA extracted from virions. Pulse-chase experiments indicated that nascent DNA acquires the sedimentation rate and buoyant density of viral DNA within 30 to 40 min after its synthesis. (iii) Electron microscopic studies indicated that the DNA extracted from cells replicating viral DNA and banding at the density of viral DNA contained: (a) linear, full-size molecules with internal gaps and single-stranded regions at termini; (b) molecules with lariats, consisting of a linear segment up to 2x the size of mature DNA and a ring ranging from 0.5 x 10(6) to 100 x 10(6) in molecular weight, showing continuous and discontinuous forks; (c) circular, double-stranded molecules, both full-size and multiples of 18 x 10(6) in molecular weight, but without forks or loops; (d) molecules showing \"eye\" and \"D\" loops at or near one end of the DNA; (e) large, tangled masses of DNA, similar to those observed for T4 and pseudorabies virus replicating DNAs, containing loops and continuous and discontinuous forks. The electron micrographs are consistent with the hypothesis that the single-stranded ends on the DNA anneal to form a hairpin, that the DNA synthesis is initiated at or near that end and proceeds bidirectionally to form a lariat, and that resulting progeny derived by semiconservative replication are \"head-to-head\" and \"tail-to-tail\" dimers.", "contents": "Anatomy of herpes simplex virus DNA VIII. Properties of the replicating DNA. This paper concerns the properties of herpes simplex virus 1 DNA replicating in HEp-2 and human embryonic lung cells. The results were as follows. (i) Only a small fraction of input viral DNA entered the replicative pool. The bulk of the input viral DNA cosedimented with marker viral DNA and did not appear to be degraded or dissociated into L and S components. (ii) Nascent DNA sedimented faster and banded at a higher density than that of mature viral DNA extracted from virions. Pulse-chase experiments indicated that nascent DNA acquires the sedimentation rate and buoyant density of viral DNA within 30 to 40 min after its synthesis. (iii) Electron microscopic studies indicated that the DNA extracted from cells replicating viral DNA and banding at the density of viral DNA contained: (a) linear, full-size molecules with internal gaps and single-stranded regions at termini; (b) molecules with lariats, consisting of a linear segment up to 2x the size of mature DNA and a ring ranging from 0.5 x 10(6) to 100 x 10(6) in molecular weight, showing continuous and discontinuous forks; (c) circular, double-stranded molecules, both full-size and multiples of 18 x 10(6) in molecular weight, but without forks or loops; (d) molecules showing \"eye\" and \"D\" loops at or near one end of the DNA; (e) large, tangled masses of DNA, similar to those observed for T4 and pseudorabies virus replicating DNAs, containing loops and continuous and discontinuous forks. The electron micrographs are consistent with the hypothesis that the single-stranded ends on the DNA anneal to form a hairpin, that the DNA synthesis is initiated at or near that end and proceeds bidirectionally to form a lariat, and that resulting progeny derived by semiconservative replication are \"head-to-head\" and \"tail-to-tail\" dimers."}
{"id": "PMID:196116", "title": "Persistent adenovirus infections of nonpermissive monkey cells.", "content": "Persisten infections of monkey cells have been established by using two serotypes of human adenovirus. The persistently infected cells show no morpho logical changes, but continue ot produce low titers of infectious adenovirus. The inapparent infection can, at any time, be converted to a cytolytic productive one by superinfection with simian virus 40. Persistence in this system does not appear to result from multiple rounds of lytic infection, nor is it mediated by production of defective interfering particles. The persistently infected cells do not possess the characteristics of oncogenic transformation. Results of these studies also whow that the nonpermissiveness of monkey cells to adenovirus replication can be partially overcome by infection at high multiplicity.", "contents": "Persistent adenovirus infections of nonpermissive monkey cells. Persisten infections of monkey cells have been established by using two serotypes of human adenovirus. The persistently infected cells show no morpho logical changes, but continue ot produce low titers of infectious adenovirus. The inapparent infection can, at any time, be converted to a cytolytic productive one by superinfection with simian virus 40. Persistence in this system does not appear to result from multiple rounds of lytic infection, nor is it mediated by production of defective interfering particles. The persistently infected cells do not possess the characteristics of oncogenic transformation. Results of these studies also whow that the nonpermissiveness of monkey cells to adenovirus replication can be partially overcome by infection at high multiplicity."}
{"id": "PMID:196117", "title": "DNA of Epstein-Barr virus. II. Comparison of the molecular weights of restriction endonuclease fragments of the DNA of Epstein-Barr virus strains and identification of end fragments of the B95-8 strain.", "content": "Incubation of the DNA of the B95-8 strain of Epstein-Barr virus [EBV (B95-8) DNA] with EcoRI, Hsu I, Sal I, or Kpn I restriction endonuclease yielded 8 to 15 fragments separable on 0.4% agarose gels and ranging in molecular weight from less than 1 to more than 30 x 10(6). Bam I and Bgl II yielded fragments smaller than 11 x 10(6). Preincubation of EBV (B95-8) DNA with lambda exonuclease resulted in a decrease in the Hsu I A and Sal I A and D fragments, indicating that these fragments are positioned near termini. The electrophoretic profiles of the fragments produced by cleavage of the DNA of the B95-8, HR-1, and Jijoye strains of EBV were each distinctive. The molecular weights of some EcoRI, Hsu I, and Sal I fragments from the DNA of the HR-1 strain of EBV [EBV (HR-1) DNA] and of EcoRI fragments of the DNA of the Jijoye strain of EBV were identical to that of fragments produced by cleavage of EBV (B95-8) DNA with the same enzyme, whereas others were unique to each strain. Some Hsu I, EcoRI, and Sal I fragments of EBV (HR-1) DNA and Kpn I fragments of EBV (B95-8) DNA were present in half-molar abundance relative to the majority of the fragments. In these instances, the sum of the molecular weights of the fragments was in excess of 10(8), the known molecular weight of EBV (HR-1) and (B95-8) DNA. The simplest interpretation of this finding is that each EBV (HR-1), and possibly also (B95-8), DNA preparation contains two populations of DNA molecules that differ in the arrangement of DNA sequences about a single point, such as has been described for herpes simplex virus DNA. Minor fragments could also be observed if there were more than one difference in primary structure of the DNAs. The data do not exclude more extensive heterogeneity in primary structure of the DNA of the HR-1 strain. However, the observation that the relative molar abundance of major and minor fragments of EBV (HR-1) DNA did not vary between preparations from cultures that had been maintained separately for several years favors the former hypothesis over the latter.", "contents": "DNA of Epstein-Barr virus. II. Comparison of the molecular weights of restriction endonuclease fragments of the DNA of Epstein-Barr virus strains and identification of end fragments of the B95-8 strain. Incubation of the DNA of the B95-8 strain of Epstein-Barr virus [EBV (B95-8) DNA] with EcoRI, Hsu I, Sal I, or Kpn I restriction endonuclease yielded 8 to 15 fragments separable on 0.4% agarose gels and ranging in molecular weight from less than 1 to more than 30 x 10(6). Bam I and Bgl II yielded fragments smaller than 11 x 10(6). Preincubation of EBV (B95-8) DNA with lambda exonuclease resulted in a decrease in the Hsu I A and Sal I A and D fragments, indicating that these fragments are positioned near termini. The electrophoretic profiles of the fragments produced by cleavage of the DNA of the B95-8, HR-1, and Jijoye strains of EBV were each distinctive. The molecular weights of some EcoRI, Hsu I, and Sal I fragments from the DNA of the HR-1 strain of EBV [EBV (HR-1) DNA] and of EcoRI fragments of the DNA of the Jijoye strain of EBV were identical to that of fragments produced by cleavage of EBV (B95-8) DNA with the same enzyme, whereas others were unique to each strain. Some Hsu I, EcoRI, and Sal I fragments of EBV (HR-1) DNA and Kpn I fragments of EBV (B95-8) DNA were present in half-molar abundance relative to the majority of the fragments. In these instances, the sum of the molecular weights of the fragments was in excess of 10(8), the known molecular weight of EBV (HR-1) and (B95-8) DNA. The simplest interpretation of this finding is that each EBV (HR-1), and possibly also (B95-8), DNA preparation contains two populations of DNA molecules that differ in the arrangement of DNA sequences about a single point, such as has been described for herpes simplex virus DNA. Minor fragments could also be observed if there were more than one difference in primary structure of the DNAs. The data do not exclude more extensive heterogeneity in primary structure of the DNA of the HR-1 strain. However, the observation that the relative molar abundance of major and minor fragments of EBV (HR-1) DNA did not vary between preparations from cultures that had been maintained separately for several years favors the former hypothesis over the latter."}
{"id": "PMID:196119", "title": "Monoplace hyperbaric oxygen therapy for gas gangrene.", "content": "Untreated gas gangrene is a fulminating infection that can lead to extensive tissue necrosis and death. Hyperbaric oxygen, when used with antibiotics and surgical debridement, can lead to decreased mortality. Nine patients with gas gangrene proven by positive clostridial cultures have been treated at St Luke's Hospital of Kansas City with a mortality of 11.1%. A case of gas gangrene developing from a perirectal abscess is presented.", "contents": "Monoplace hyperbaric oxygen therapy for gas gangrene. Untreated gas gangrene is a fulminating infection that can lead to extensive tissue necrosis and death. Hyperbaric oxygen, when used with antibiotics and surgical debridement, can lead to decreased mortality. Nine patients with gas gangrene proven by positive clostridial cultures have been treated at St Luke's Hospital of Kansas City with a mortality of 11.1%. A case of gas gangrene developing from a perirectal abscess is presented."}
{"id": "PMID:196120", "title": "Protective action of estrogen in endotoxin shock.", "content": "Protective action of conjugated equine estrogen (CEE) against endotoxin shock was admitted in mice. Male DDN strain mice pretreated intraperitoneally with 2 mg of CEE showed various survival rates according to the interval between administration of CEE and endotoxin injection. Survival rates of the control were 20.4%, but in the group pretreated with CEE they were 0% at 0 hour, 26.3% at 1 hour, 33.3% at 12 hours, 55.7% at 24 hours (p less than 0.001), 10.5% at 36 hours, and 31.2% at 48 hours respectively. Mice pretreated with 2 mg of CEE before 24 hours exhibited excellent resistance to 0.5 mg endotoxin. On the other hand, the hemodynamic effect of CEE was examined in six mongrel dogs, which showed little hemodynamic changes following administration of 10 mg/kg CEE for three hours observation. We speculated that the anti-shock action of CEE was due to the modification of vascular response to vasoactive substances, on the one hand it augmented the vascular contractile response to vasopressors and on the other hand it lessened the hypersensitive vasoconstriction under shock state.", "contents": "Protective action of estrogen in endotoxin shock. Protective action of conjugated equine estrogen (CEE) against endotoxin shock was admitted in mice. Male DDN strain mice pretreated intraperitoneally with 2 mg of CEE showed various survival rates according to the interval between administration of CEE and endotoxin injection. Survival rates of the control were 20.4%, but in the group pretreated with CEE they were 0% at 0 hour, 26.3% at 1 hour, 33.3% at 12 hours, 55.7% at 24 hours (p less than 0.001), 10.5% at 36 hours, and 31.2% at 48 hours respectively. Mice pretreated with 2 mg of CEE before 24 hours exhibited excellent resistance to 0.5 mg endotoxin. On the other hand, the hemodynamic effect of CEE was examined in six mongrel dogs, which showed little hemodynamic changes following administration of 10 mg/kg CEE for three hours observation. We speculated that the anti-shock action of CEE was due to the modification of vascular response to vasoactive substances, on the one hand it augmented the vascular contractile response to vasopressors and on the other hand it lessened the hypersensitive vasoconstriction under shock state."}
{"id": "PMID:196123", "title": "Effect of propranolol on blood pressure and plasma renin concentration in renovascular hypertensive rats.", "content": "The effect of chronic oral administration of propranolol (39--80 mg/Kg/day, for 21--27 days) on blood pressure, plasma renin concentration, and heart rate were studied in 2 types of renovascular hypertensive rats; one-kidney type with normal plasma renin and two-kidney type with high plasma renin. No significant change was observed in the blood pressure of either model during the administration of propranolol in spite of a significant reduction of heart rate. Plasma renin concentration showed a trend of suppression in two-kidney type rats, but this change was not significant. There was no suppression in one-kidney type rats. These results suggest that the beta-adrenergic system may not play a major role either in regulating plasma renin level or in maintaining the blood pressure in renovascular hypertensive rats.", "contents": "Effect of propranolol on blood pressure and plasma renin concentration in renovascular hypertensive rats. The effect of chronic oral administration of propranolol (39--80 mg/Kg/day, for 21--27 days) on blood pressure, plasma renin concentration, and heart rate were studied in 2 types of renovascular hypertensive rats; one-kidney type with normal plasma renin and two-kidney type with high plasma renin. No significant change was observed in the blood pressure of either model during the administration of propranolol in spite of a significant reduction of heart rate. Plasma renin concentration showed a trend of suppression in two-kidney type rats, but this change was not significant. There was no suppression in one-kidney type rats. These results suggest that the beta-adrenergic system may not play a major role either in regulating plasma renin level or in maintaining the blood pressure in renovascular hypertensive rats."}
{"id": "PMID:196131", "title": "Enterotoxigenic Escherichia coli diarrhea of travelers: a prospective study of American Peace Corps volunteers.", "content": "Travelers' diarrhea was studied prospectively in a group of 39 American Peace Corps Volunteers (PCVs) during their first five weeks in Kenya. Twenty-seven developed diarrheal disease and 12 remained well. Multiple episodes were documented in 11 of the symptomatic volunteers. Enterotoxigenic Escherichia coli of many serotypes producing heat-labile and/or heat-stable enterotoxin were isolated from 17 of the 27 volunteers with diarrhea and from 1 of the 12 well volunteers. The enterotoxigenic E. coli were more likely to be antibiotic sensitive than the non-enterotoxigenic E. coli. A serum antibody rise to the heat-labile toxin (LT) was detected in six symptomatic volunteers, five of whom had a positive culture for LT-producing E. coli, and from one asymptomatic, culture negative volunteer. Salmonella cubana was isolated from two volunteers, and three volunteers had serologic evidence of infection with human reovirus-like (rotavirus) agent. This study confirms the role of enterotoxigenic E. coli as a major cause of travelers' diarrhea and suggests that the disease is similar in widely separated geographic areas.", "contents": "Enterotoxigenic Escherichia coli diarrhea of travelers: a prospective study of American Peace Corps volunteers. Travelers' diarrhea was studied prospectively in a group of 39 American Peace Corps Volunteers (PCVs) during their first five weeks in Kenya. Twenty-seven developed diarrheal disease and 12 remained well. Multiple episodes were documented in 11 of the symptomatic volunteers. Enterotoxigenic Escherichia coli of many serotypes producing heat-labile and/or heat-stable enterotoxin were isolated from 17 of the 27 volunteers with diarrhea and from 1 of the 12 well volunteers. The enterotoxigenic E. coli were more likely to be antibiotic sensitive than the non-enterotoxigenic E. coli. A serum antibody rise to the heat-labile toxin (LT) was detected in six symptomatic volunteers, five of whom had a positive culture for LT-producing E. coli, and from one asymptomatic, culture negative volunteer. Salmonella cubana was isolated from two volunteers, and three volunteers had serologic evidence of infection with human reovirus-like (rotavirus) agent. This study confirms the role of enterotoxigenic E. coli as a major cause of travelers' diarrhea and suggests that the disease is similar in widely separated geographic areas."}
{"id": "PMID:196132", "title": "[Drug treatment of hyperlipemia in middle-aged and old persons with ischemic heart disease].", "content": "The examination was conducted in 1048 patients with the ischaemic heart disease. Both males, and females displayed most frequently Type II hyperlipidemia. Type IV was more frequent in males, than in females. The incidence of Types IIa and IIb depended on the stage of coronary atherosclerosis, the age and sex of the patients. The concomitant diseases were found to influence the incidence of hyperlipidemia. Among the tested drugs administered in a course of therapy of 4 weeks atromidine proved to be most effective for the examined types of hyperlipidemia (IIa, IIb, IV). Hyperlipidemia relapsed in 1/3 of the patients within 1 year.", "contents": "[Drug treatment of hyperlipemia in middle-aged and old persons with ischemic heart disease]. The examination was conducted in 1048 patients with the ischaemic heart disease. Both males, and females displayed most frequently Type II hyperlipidemia. Type IV was more frequent in males, than in females. The incidence of Types IIa and IIb depended on the stage of coronary atherosclerosis, the age and sex of the patients. The concomitant diseases were found to influence the incidence of hyperlipidemia. Among the tested drugs administered in a course of therapy of 4 weeks atromidine proved to be most effective for the examined types of hyperlipidemia (IIa, IIb, IV). Hyperlipidemia relapsed in 1/3 of the patients within 1 year."}
{"id": "PMID:196133", "title": "[Antiarrhythmic activity of adrenergic blockaders with different mechanisms of action].", "content": "Experiments have demonstrated that Alfeprol arrests atrial fibrillation in dogs induced by electric stimulation of the heart, and atrial fibrillation in cats modelled by Akonitine application; it suppresses ventricular tachycardia in dogs occurring following an occlusion of the branches of coronary arteries, and in cats when induced by strophantin intoxication; it prevents fatal ventricular fibrillation in rats poisoned by calcium chloride. The antiarrhythmic effect of Anaprille was not so persistent and manifested itself only in cases of some particular rhythm disorders. Ornid displayed no antiarrhythmic activity. The blocking of adrenergic innervation of the heart by means of beta-adrenergic blockers (Alfeprol, Anaprilline) and sympatholytic (Reserpine, Ornid) considerably increased the animals tolerance of the toxic effect of strophantin, decreasing its arrhythmogenic effect in particular. The mechanisms of the antiarrhythmic effect of antiadrenergic agents are discussed along with the possibilities of their employment for the correction of cardiac sensitivity of glycosides.", "contents": "[Antiarrhythmic activity of adrenergic blockaders with different mechanisms of action]. Experiments have demonstrated that Alfeprol arrests atrial fibrillation in dogs induced by electric stimulation of the heart, and atrial fibrillation in cats modelled by Akonitine application; it suppresses ventricular tachycardia in dogs occurring following an occlusion of the branches of coronary arteries, and in cats when induced by strophantin intoxication; it prevents fatal ventricular fibrillation in rats poisoned by calcium chloride. The antiarrhythmic effect of Anaprille was not so persistent and manifested itself only in cases of some particular rhythm disorders. Ornid displayed no antiarrhythmic activity. The blocking of adrenergic innervation of the heart by means of beta-adrenergic blockers (Alfeprol, Anaprilline) and sympatholytic (Reserpine, Ornid) considerably increased the animals tolerance of the toxic effect of strophantin, decreasing its arrhythmogenic effect in particular. The mechanisms of the antiarrhythmic effect of antiadrenergic agents are discussed along with the possibilities of their employment for the correction of cardiac sensitivity of glycosides."}
{"id": "PMID:196135", "title": "[The pathophysiology of recurrent herpes simplex virus disease (author's transl)].", "content": "Clinical recurrence of herpes simplex virus (HSV) disease may occur when latent HSV escapes the state of latency and begins again to enter the lytic reproduction cycle. Recent investigation revealed HSV latency in peripheral sensory ganglia and an intra-axonal viral transport between the periphery and the appropriate sensory ganglia. As all previous attempts to demonstrate latent HSV in ocular structures have failed, the neuronal hypothesis for HSV latency and recurrences is the most probable. The consequences for therapy and prophylaxis of HSV disease are discussed.", "contents": "[The pathophysiology of recurrent herpes simplex virus disease (author's transl)]. Clinical recurrence of herpes simplex virus (HSV) disease may occur when latent HSV escapes the state of latency and begins again to enter the lytic reproduction cycle. Recent investigation revealed HSV latency in peripheral sensory ganglia and an intra-axonal viral transport between the periphery and the appropriate sensory ganglia. As all previous attempts to demonstrate latent HSV in ocular structures have failed, the neuronal hypothesis for HSV latency and recurrences is the most probable. The consequences for therapy and prophylaxis of HSV disease are discussed."}
{"id": "PMID:196144", "title": "Glomus jugulare tumor.", "content": "A review has been made of the current recommendations for treatment of glomus tumors involving the ear. Thirty cases treated in our clinic have been reviewed, comprised of 8 glomus tympanicum and 22 glomus jugulare tumors. We recommend surgical excision as primary treatment for glomus tympanicum tumors and high voltage radiotherapy as primary treatment for glomus jugulare tumors. Visible residual tumor following adequate radiotherapy may remain unchanged for many years. Some cases that do not show a response to high voltage radiation may be suitable for secondary radical surgical treatment. Fortunately, we have not yet encountered a case of glomus jugulare tumor with nonresponse to high voltage radiation in the doses recommended. Long term follow-up is important.", "contents": "Glomus jugulare tumor. A review has been made of the current recommendations for treatment of glomus tumors involving the ear. Thirty cases treated in our clinic have been reviewed, comprised of 8 glomus tympanicum and 22 glomus jugulare tumors. We recommend surgical excision as primary treatment for glomus tympanicum tumors and high voltage radiotherapy as primary treatment for glomus jugulare tumors. Visible residual tumor following adequate radiotherapy may remain unchanged for many years. Some cases that do not show a response to high voltage radiation may be suitable for secondary radical surgical treatment. Fortunately, we have not yet encountered a case of glomus jugulare tumor with nonresponse to high voltage radiation in the doses recommended. Long term follow-up is important."}
{"id": "PMID:196145", "title": "Surgical management of vagal chemodectomas.", "content": "Vagal chemodectomas (tumors of the vagal glomus body) are histologically benign and insensitive to radiation therapy. Unless properly managed, these tumors may become life-threatening because of their eventual impingement on surrounding structures, particularly contents of the cranial vault. Patients with chemodectomas of the skull base may be surgically treated without significant functional or cosmetic loss, provided the surgeon possesses the following surgical abilities: 1. temporal bone dissection capabilities; 2. microsurgical skills, including techniques of middle ear reconstruction and neurovascular anastomosis; 3. implementation of simultaneous multiple approaches to the skull base and infratemporal fossa; and 4. the capability of managing technically inherent intraoperative and postoperative problems. Experience from nine patients, all successfully treated surgically, will be summarized.", "contents": "Surgical management of vagal chemodectomas. Vagal chemodectomas (tumors of the vagal glomus body) are histologically benign and insensitive to radiation therapy. Unless properly managed, these tumors may become life-threatening because of their eventual impingement on surrounding structures, particularly contents of the cranial vault. Patients with chemodectomas of the skull base may be surgically treated without significant functional or cosmetic loss, provided the surgeon possesses the following surgical abilities: 1. temporal bone dissection capabilities; 2. microsurgical skills, including techniques of middle ear reconstruction and neurovascular anastomosis; 3. implementation of simultaneous multiple approaches to the skull base and infratemporal fossa; and 4. the capability of managing technically inherent intraoperative and postoperative problems. Experience from nine patients, all successfully treated surgically, will be summarized."}
{"id": "PMID:196159", "title": "Alterations in lipid constituents during growth of Mycobacterium smegmatis CDC 46 and Mycobacterium phlei ATCC 354.", "content": "Phospholipids of Mycobacterium phlei ATCC 354 and Mycobacterium smegmatis CDC 46 consist of cardiolipin, phosphatidyl ethanolamine, tri-acylated dimannophosphoinositide, tetra-acylated dimannophosphoinositide and tetra-acylated pentamannosphosphoinositide. A comparative study of lipid patterns of M. phlei ATCC 354 and of M. smegmatis CDC 46 in relation to age of culture revealed higher total lipid level and increased activity of malate-vitamin K reductase, a phospholipid requiring enzyme, during the early logarithmic growth phase of the former. No appreciable change occurred in the latter. The high total lipid content coincides with an increase in phospholipid, brought about apparently by the increase in malate-vitamin K reductase. Changes in cardiolipin and phosphatidyl ethanolamine appeared to be unique to M. phlei ATCC 354. However, in both bacterial species, a decrease in glyceride and a progressive increase in tuberculostearic acid with a concomitant decrease in oleic acid, occurred with ageing.", "contents": "Alterations in lipid constituents during growth of Mycobacterium smegmatis CDC 46 and Mycobacterium phlei ATCC 354. Phospholipids of Mycobacterium phlei ATCC 354 and Mycobacterium smegmatis CDC 46 consist of cardiolipin, phosphatidyl ethanolamine, tri-acylated dimannophosphoinositide, tetra-acylated dimannophosphoinositide and tetra-acylated pentamannosphosphoinositide. A comparative study of lipid patterns of M. phlei ATCC 354 and of M. smegmatis CDC 46 in relation to age of culture revealed higher total lipid level and increased activity of malate-vitamin K reductase, a phospholipid requiring enzyme, during the early logarithmic growth phase of the former. No appreciable change occurred in the latter. The high total lipid content coincides with an increase in phospholipid, brought about apparently by the increase in malate-vitamin K reductase. Changes in cardiolipin and phosphatidyl ethanolamine appeared to be unique to M. phlei ATCC 354. However, in both bacterial species, a decrease in glyceride and a progressive increase in tuberculostearic acid with a concomitant decrease in oleic acid, occurred with ageing."}
{"id": "PMID:196160", "title": "Adenosine 3',5'-monophosphate in Mycobacterium phlei and Mycobacterium tuberculosis H37Ra.", "content": "Adenosine 3',5'-monophosphate (cAMP) is present in slow growing as well as fast growing mycobacteria. Apparently there does not seem to be any direct relationship between either intra- or extracellular cAMP content with the growth rate of bacilli. As compared to that of E. coli grown on a similar energy source, cAMP content is much higher in mycobacteria. cAMP content inside the cells remains unaltered throughout the growth period and this may be due to lack of complete utilization of the major energy source, glycerol. Glucose when added to the cells, suspended in phosphate buffer, caused a remarkable decrease in intracellular cAMP content, a phenomenon well established in other bacteria.", "contents": "Adenosine 3',5'-monophosphate in Mycobacterium phlei and Mycobacterium tuberculosis H37Ra. Adenosine 3',5'-monophosphate (cAMP) is present in slow growing as well as fast growing mycobacteria. Apparently there does not seem to be any direct relationship between either intra- or extracellular cAMP content with the growth rate of bacilli. As compared to that of E. coli grown on a similar energy source, cAMP content is much higher in mycobacteria. cAMP content inside the cells remains unaltered throughout the growth period and this may be due to lack of complete utilization of the major energy source, glycerol. Glucose when added to the cells, suspended in phosphate buffer, caused a remarkable decrease in intracellular cAMP content, a phenomenon well established in other bacteria."}
{"id": "PMID:196161", "title": "Detection of precursors of quinolinic acid in Escherichia coli.", "content": "A technique is described which allows the detection of precursors of quinolinic acid produced by Escherichia coli, independent of a bioassay. This is based on a double autoradiogram utilizing radioactive aspartic acid and fructose-1,6-diphosphate (as a source of dihydroxyacetone phosphate). Six radioactive spots are derived from aspartic acid and four are derived from fructose-1,6-diphosphate. The latter four spots correspond to four of the former spots in migration in each of two solvent systems. The significance of these data relative to genetic and enzymatic data is discussed.", "contents": "Detection of precursors of quinolinic acid in Escherichia coli. A technique is described which allows the detection of precursors of quinolinic acid produced by Escherichia coli, independent of a bioassay. This is based on a double autoradiogram utilizing radioactive aspartic acid and fructose-1,6-diphosphate (as a source of dihydroxyacetone phosphate). Six radioactive spots are derived from aspartic acid and four are derived from fructose-1,6-diphosphate. The latter four spots correspond to four of the former spots in migration in each of two solvent systems. The significance of these data relative to genetic and enzymatic data is discussed."}
{"id": "PMID:196162", "title": "Characterization of simian virus 40 transformed African green monkey cells (CV-1). I. Defective virion and viral genome.", "content": "Several clones of SV40 transformed CV-1 cells have been characterized for the production of T- and V-antigens and for the state of viral genome. The transformed CV-1 cells failed to produce infectious virions as assayed after sonication or cocultivation and fusion with normal CV-1 cells, and were resistant to super-infection by SV40. Some clones of the transformed cells contained V-antigens. The population of V-antigen positive cells varied from 0 to 100% depending on the passage number while the T-antigen positive cells were always 100%. The virions isolated from the transformed cells were similar in morphology to complete SV40, but lighter in density than complete SV40. In one clone, a small amount of SV40 DNA was detectable in a free state while a large proportion of the DNA hybridizable with SV40 3H cRNA was linearly integrated into the cell DNA. The free SV40 DNA was noninfectious, closed circular DNA with a size smaller than infectious SV40 DNA component I. Since the cell extracts of the transformed cells contained an agent(s) which induced T- and V-antigens in normal CV-1 cells, it was suggested that the SV40 transformed CV-1 cells contained free as well as integrated defective SV40 genomes responsible for the synthesis of T- and V-antigens.", "contents": "Characterization of simian virus 40 transformed African green monkey cells (CV-1). I. Defective virion and viral genome. Several clones of SV40 transformed CV-1 cells have been characterized for the production of T- and V-antigens and for the state of viral genome. The transformed CV-1 cells failed to produce infectious virions as assayed after sonication or cocultivation and fusion with normal CV-1 cells, and were resistant to super-infection by SV40. Some clones of the transformed cells contained V-antigens. The population of V-antigen positive cells varied from 0 to 100% depending on the passage number while the T-antigen positive cells were always 100%. The virions isolated from the transformed cells were similar in morphology to complete SV40, but lighter in density than complete SV40. In one clone, a small amount of SV40 DNA was detectable in a free state while a large proportion of the DNA hybridizable with SV40 3H cRNA was linearly integrated into the cell DNA. The free SV40 DNA was noninfectious, closed circular DNA with a size smaller than infectious SV40 DNA component I. Since the cell extracts of the transformed cells contained an agent(s) which induced T- and V-antigens in normal CV-1 cells, it was suggested that the SV40 transformed CV-1 cells contained free as well as integrated defective SV40 genomes responsible for the synthesis of T- and V-antigens."}
{"id": "PMID:196165", "title": "Oestrogens and menopausal and postmenopausal women.", "content": "The majority of women experience a variety of symptoms at the time of the menopause, but these are frequently regarded as being unworthy of management by their doctors. Recent reports of a possible association between exogenous oestrogens and endometrial carcinoma have increased professional reluctance to prescribe oestrogens for menopausal symptoms. This report describes the initial 50 patients who have attended a special clinic established to manage symptomatic menopausal women; common complaints included hot flushes, lack of energy, altered temperament, dyspareunia and headache. Oestrogen therapy was effective in the alleviation of symptoms and the practical aspects of oestrogen use are discussed. It is recommended that with due recognition of its potential complications, oestrogen therapy should be made available to symptomatic menopausal women, and that it requires further study in regard to its place in the long-term prophylaxis of osteoporosis.", "contents": "Oestrogens and menopausal and postmenopausal women. The majority of women experience a variety of symptoms at the time of the menopause, but these are frequently regarded as being unworthy of management by their doctors. Recent reports of a possible association between exogenous oestrogens and endometrial carcinoma have increased professional reluctance to prescribe oestrogens for menopausal symptoms. This report describes the initial 50 patients who have attended a special clinic established to manage symptomatic menopausal women; common complaints included hot flushes, lack of energy, altered temperament, dyspareunia and headache. Oestrogen therapy was effective in the alleviation of symptoms and the practical aspects of oestrogen use are discussed. It is recommended that with due recognition of its potential complications, oestrogen therapy should be made available to symptomatic menopausal women, and that it requires further study in regard to its place in the long-term prophylaxis of osteoporosis."}
{"id": "PMID:196167", "title": "[Experimental studies of the effects of Seda-Kneipp on the sleep of sleep disturbed subjects; implications for the treatment of different sleep disturbances (author's transl)].", "content": "Seda-Kneipp a compound preparation of valerian and hops was given to sleep disturbed subjects during the second or third of three consecutive nights disturbed by heavy traffic noise. Prior drug administration reduced the noise induced disturbance of sleep stage patterns: slow-wave sleep and stage REM increased. It is recommended that the initial treatment of severe insomnia by \"strong\" sleeping pills should be followed by a period during which \"weak\" sleeping pills are given before the drug administration finally is discontinued.", "contents": "[Experimental studies of the effects of Seda-Kneipp on the sleep of sleep disturbed subjects; implications for the treatment of different sleep disturbances (author's transl)]. Seda-Kneipp a compound preparation of valerian and hops was given to sleep disturbed subjects during the second or third of three consecutive nights disturbed by heavy traffic noise. Prior drug administration reduced the noise induced disturbance of sleep stage patterns: slow-wave sleep and stage REM increased. It is recommended that the initial treatment of severe insomnia by \"strong\" sleeping pills should be followed by a period during which \"weak\" sleeping pills are given before the drug administration finally is discontinued."}
{"id": "PMID:196168", "title": "[Therapy of hyperlipoproteinemia type II with Xantinol-nicotinate (author's transl)].", "content": "In 61 out-patients with hyperlipoproteinemia type II the action of 50 mg Xantinol-nicotinate per kg body weight on lipids of plasma and lipoproteins was investigated in a three week trial. The results of six patients had been discharged: two patients failed to attend the follow-up examinations, in four patients a lipid lowering effect could not be demonstrated. 40 Type IIa patients and 15 Type IIb patients were examined. In this two groups cholesterol, phospholipids and triglycerides of plasma were significantly lowered. In Type IIa hyperlipoproteinemia mainly the LDL lipids and in Type IIb additionally the VLDL lipids decreased. In Type IIb patients the decrease of lipids were more rapid than in Type IIa patients. This effect is interpreted by the short half life of VLDL. Withdrawel of the drug resulted in an increase of the lipids to the mean values of the untreated patients within ten days.", "contents": "[Therapy of hyperlipoproteinemia type II with Xantinol-nicotinate (author's transl)]. In 61 out-patients with hyperlipoproteinemia type II the action of 50 mg Xantinol-nicotinate per kg body weight on lipids of plasma and lipoproteins was investigated in a three week trial. The results of six patients had been discharged: two patients failed to attend the follow-up examinations, in four patients a lipid lowering effect could not be demonstrated. 40 Type IIa patients and 15 Type IIb patients were examined. In this two groups cholesterol, phospholipids and triglycerides of plasma were significantly lowered. In Type IIa hyperlipoproteinemia mainly the LDL lipids and in Type IIb additionally the VLDL lipids decreased. In Type IIb patients the decrease of lipids were more rapid than in Type IIa patients. This effect is interpreted by the short half life of VLDL. Withdrawel of the drug resulted in an increase of the lipids to the mean values of the untreated patients within ten days."}
{"id": "PMID:196179", "title": "In vitro metabolism of vitamin D3 by isolated liver cells.", "content": "Liver cells were prepared from rats fed a rachitogenic diet to investigate the hepatic metabolism of [alpha-1,2-3H2] vitamin D3. Rat hepatocytes suspended in Hanks medium rapidly took up labeled vitamin D3 from the incubation medium and converted this sterol to various metabolites, including 25-hydroxy vitamin D3 (25-OH-D3). There was steady increment in the cellular production of 25-OH-D3 and of the more polar metabolites of vitamin D3 over 3 hr of incubation as determined by thin layer chromatography. Neither the addition of cyclic nucleotides or dexamethasone to, nor the removal of calcium or phosphate from the medium resulted in changes in the rate of conversion of vitamin D3 to its products. Rats pretreated with sodium diphenylhydantoin converted labeled vitamin D3 to its metabolites at the same rate as control rats. These data indicate that isolated liver cells retain the capacity for vitamin D3 hydroxylation, but suggest that the rate of this process does not undergo rapid changes in response to metabolic stimulation.", "contents": "In vitro metabolism of vitamin D3 by isolated liver cells. Liver cells were prepared from rats fed a rachitogenic diet to investigate the hepatic metabolism of [alpha-1,2-3H2] vitamin D3. Rat hepatocytes suspended in Hanks medium rapidly took up labeled vitamin D3 from the incubation medium and converted this sterol to various metabolites, including 25-hydroxy vitamin D3 (25-OH-D3). There was steady increment in the cellular production of 25-OH-D3 and of the more polar metabolites of vitamin D3 over 3 hr of incubation as determined by thin layer chromatography. Neither the addition of cyclic nucleotides or dexamethasone to, nor the removal of calcium or phosphate from the medium resulted in changes in the rate of conversion of vitamin D3 to its products. Rats pretreated with sodium diphenylhydantoin converted labeled vitamin D3 to its metabolites at the same rate as control rats. These data indicate that isolated liver cells retain the capacity for vitamin D3 hydroxylation, but suggest that the rate of this process does not undergo rapid changes in response to metabolic stimulation."}
{"id": "PMID:196180", "title": "Activation of rat erythrocyte phosphofructokinase by AMP and by non-physiological concentrations of cyclic AMP.", "content": "Cyclic AMP (300 micron) activates phosphofructokinase from dialyzed haemolysates of mature rat erythrocytes. The main conclusions are: a) Cyclic AMP, at pH 7.1 and low concentrations of fructose-6-phosphate, is able to reverse the inhibition produced by different amounts of ATP (up to 1.5 mM). b) The cyclic nucleotide is a positive allosteric effector of the enzyme as shown by the displacement of sigmoidal fructose-6-phosphate saturation curve to hyperbolic kinetics in the presence of inhibitory concentrations (1.5 mM) of ATP.c) Cyclic AMP has no significant influence as deinhibitor of phosphofructokinase either at pH 7.1 and non-inhibitory levels (0.25 mM) of ATP or at pH 8.1 and inhibitory (1.5 mM) or non-inhibitory (0.25 mM) concentrations of ATP. Similar conclusions were obtained with 300 micron AMP but not at a lower concentration (3 micron) with both nucleotides. The comparison of cyclic AMP result with those obtained under similar concentrations of AMP suggest that cyclic AMP is really only an \"in vitro\" modulator of the enzyme from rat erythrocytes, presumably at an AMP regulatory stie, since non-physiological concentrations are required to act as deinhibitor.", "contents": "Activation of rat erythrocyte phosphofructokinase by AMP and by non-physiological concentrations of cyclic AMP. Cyclic AMP (300 micron) activates phosphofructokinase from dialyzed haemolysates of mature rat erythrocytes. The main conclusions are: a) Cyclic AMP, at pH 7.1 and low concentrations of fructose-6-phosphate, is able to reverse the inhibition produced by different amounts of ATP (up to 1.5 mM). b) The cyclic nucleotide is a positive allosteric effector of the enzyme as shown by the displacement of sigmoidal fructose-6-phosphate saturation curve to hyperbolic kinetics in the presence of inhibitory concentrations (1.5 mM) of ATP.c) Cyclic AMP has no significant influence as deinhibitor of phosphofructokinase either at pH 7.1 and non-inhibitory levels (0.25 mM) of ATP or at pH 8.1 and inhibitory (1.5 mM) or non-inhibitory (0.25 mM) concentrations of ATP. Similar conclusions were obtained with 300 micron AMP but not at a lower concentration (3 micron) with both nucleotides. The comparison of cyclic AMP result with those obtained under similar concentrations of AMP suggest that cyclic AMP is really only an \"in vitro\" modulator of the enzyme from rat erythrocytes, presumably at an AMP regulatory stie, since non-physiological concentrations are required to act as deinhibitor."}
{"id": "PMID:196181", "title": "Preparation and characterization of isolated parenchymal cells from guinea pig liver.", "content": "1. A method is described for the preparation of isolated cells from guinea pig liver. This involved perfusion in situ, in the non-physiological direction, with collagenase. 2. The cell yield was 20--30%, comparable with those from the livers of other species. 3. The ratio of lactate dehydrogenase to glutamate dehydrogenase in the cells was similar to that in vivo, indicating that there was negligible leakage of cytoplasmic enzymes. 4. The concentrations of K+ and adenine nucleotides were initially lower than in the perfused liver; normal values were obtained on incubation, particularly in the presence of substrate. 5. The L-lactate: pyruvate ratio is 16:1, close to established values. The total beta-hydroxybutyrate: acetoacetate ratio indicates that the mitochondrial redox state is more oxidised than in the perfused liver, but the intracellular ratio is similar to that of the intact liver. 6. Rates of gluconeogenesis and ureogenesis, are within the physiological range. Maximal gluconeogeneis from L-lactate was preceded by a lag period. L-lysine stimulated glucose production from L-lactate but did not abolish the lag phase. 7. The effects of aminooxyacetate and octanoate on L-lactate gluconeogenesis were similar to those in the perfused liver.", "contents": "Preparation and characterization of isolated parenchymal cells from guinea pig liver. 1. A method is described for the preparation of isolated cells from guinea pig liver. This involved perfusion in situ, in the non-physiological direction, with collagenase. 2. The cell yield was 20--30%, comparable with those from the livers of other species. 3. The ratio of lactate dehydrogenase to glutamate dehydrogenase in the cells was similar to that in vivo, indicating that there was negligible leakage of cytoplasmic enzymes. 4. The concentrations of K+ and adenine nucleotides were initially lower than in the perfused liver; normal values were obtained on incubation, particularly in the presence of substrate. 5. The L-lactate: pyruvate ratio is 16:1, close to established values. The total beta-hydroxybutyrate: acetoacetate ratio indicates that the mitochondrial redox state is more oxidised than in the perfused liver, but the intracellular ratio is similar to that of the intact liver. 6. Rates of gluconeogenesis and ureogenesis, are within the physiological range. Maximal gluconeogeneis from L-lactate was preceded by a lag period. L-lysine stimulated glucose production from L-lactate but did not abolish the lag phase. 7. The effects of aminooxyacetate and octanoate on L-lactate gluconeogenesis were similar to those in the perfused liver."}
{"id": "PMID:196182", "title": "Changes in the collagenolytic activity released by primary VX-2 carcinoma cultures as a function of tumor growth.", "content": "Serum-free media of minced tissue cultures of VX-2 rabbit carcinoma contained a specific collagenolytic activity capable of releasing soluble radioactive peptides from [14C]-labeled collagen fibrils. It was also capable of reducing the viscosity of acid-soluble collagen solutions by cleaving the tropocollagen (TC) molecules primarily at one site to TCA (75%) and TCB (25%) fragments. Three chromatographic fractions were separated by gel filtration: F1, (MW 85-110,000) present in larger amounts in early cultures of younger tumor tissue; F2, (MW-35-40,000) the major component with maximum production in the day 3 media of younger and advanced tumor tissues; F3, (MW 18-22,000) the minor component. Early cultures of younger tumor tissue contained a latent collagenase and were subject to trypsin activation suggesting the presence of inactive enzyme precursors or an enzyme-inhibitor complex.", "contents": "Changes in the collagenolytic activity released by primary VX-2 carcinoma cultures as a function of tumor growth. Serum-free media of minced tissue cultures of VX-2 rabbit carcinoma contained a specific collagenolytic activity capable of releasing soluble radioactive peptides from [14C]-labeled collagen fibrils. It was also capable of reducing the viscosity of acid-soluble collagen solutions by cleaving the tropocollagen (TC) molecules primarily at one site to TCA (75%) and TCB (25%) fragments. Three chromatographic fractions were separated by gel filtration: F1, (MW 85-110,000) present in larger amounts in early cultures of younger tumor tissue; F2, (MW-35-40,000) the major component with maximum production in the day 3 media of younger and advanced tumor tissues; F3, (MW 18-22,000) the minor component. Early cultures of younger tumor tissue contained a latent collagenase and were subject to trypsin activation suggesting the presence of inactive enzyme precursors or an enzyme-inhibitor complex."}
{"id": "PMID:196183", "title": "Experimental phenylketonuria: metabolic studies in rat liver.", "content": "The \"in vivo\" effects of L-phenylalanine on the gluconeogenic pathway in the liver of fasted rats with experimentally induced phenylketonuria-like characteristics have been investigated. Significant increases of the fructose 6-phosphate, glucose 6-phosphate and glucose concentrations were observed. The study of the effect of L-phenylalanine on the cytoplasmic and mitochondrial redox state and energy charge showed an increase in the mitochondrial NAD+/NADH ratio while the energy charge was virtually unchanged. The effects of phenylalanine and its metabolic derivatives (phenylacetate, phenylethylamine, phenyl-lactate, o-hydroxyphenylacetate and phenylpyruvate) on the activity of lactate dehydrogenase (EC 1.1.1.27), malate dehydrogenase (EC 1.1.1.37) and 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in rat liver have been also investigated. Phenylpyruvate inhibited the lactate dehydrogenase activity with a Ki of 5.3 mM. Phenylpyruvate also inhibited both the mitochondrial (Ki = 4 mM) and cytoplasmic (Ki = 5 mM) malate dehydrogenase activities. Phenylpyruvate, phenylacetate and o-hydroxyphenylacetate inhibited the 3-hydroxybutyrate dehydrogenase activity with Ki values of 0.7, 6.0 and 9.5 mM respectively.", "contents": "Experimental phenylketonuria: metabolic studies in rat liver. The \"in vivo\" effects of L-phenylalanine on the gluconeogenic pathway in the liver of fasted rats with experimentally induced phenylketonuria-like characteristics have been investigated. Significant increases of the fructose 6-phosphate, glucose 6-phosphate and glucose concentrations were observed. The study of the effect of L-phenylalanine on the cytoplasmic and mitochondrial redox state and energy charge showed an increase in the mitochondrial NAD+/NADH ratio while the energy charge was virtually unchanged. The effects of phenylalanine and its metabolic derivatives (phenylacetate, phenylethylamine, phenyl-lactate, o-hydroxyphenylacetate and phenylpyruvate) on the activity of lactate dehydrogenase (EC 1.1.1.27), malate dehydrogenase (EC 1.1.1.37) and 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in rat liver have been also investigated. Phenylpyruvate inhibited the lactate dehydrogenase activity with a Ki of 5.3 mM. Phenylpyruvate also inhibited both the mitochondrial (Ki = 4 mM) and cytoplasmic (Ki = 5 mM) malate dehydrogenase activities. Phenylpyruvate, phenylacetate and o-hydroxyphenylacetate inhibited the 3-hydroxybutyrate dehydrogenase activity with Ki values of 0.7, 6.0 and 9.5 mM respectively."}
{"id": "PMID:196184", "title": "Influence of cyclic 3',5'-adenosine monophosphate on uracil uptake by rifampicin treated Escherichia coli cells.", "content": "Incubation of cells from a wild type strain of E. coli with 0.3 mg/ml rifampicin for 15 minutes lead to a complete inhibition of RNA synthesis measured as the uracil incorporation into the trichloroacetic acid insoluble fraction. In these rifampicin-treated cells [14C]uracil incorporation tended to decrease during a further incubation at 37 degrees. Addition of cyclic AMP increased the inactivation of the system responsible for [14C]uracil uptake. The cyclic nucleotide effect seems to be specific since ATP or 5'AMP did not increase such inactivation.", "contents": "Influence of cyclic 3',5'-adenosine monophosphate on uracil uptake by rifampicin treated Escherichia coli cells. Incubation of cells from a wild type strain of E. coli with 0.3 mg/ml rifampicin for 15 minutes lead to a complete inhibition of RNA synthesis measured as the uracil incorporation into the trichloroacetic acid insoluble fraction. In these rifampicin-treated cells [14C]uracil incorporation tended to decrease during a further incubation at 37 degrees. Addition of cyclic AMP increased the inactivation of the system responsible for [14C]uracil uptake. The cyclic nucleotide effect seems to be specific since ATP or 5'AMP did not increase such inactivation."}
{"id": "PMID:196185", "title": "Incorporation and metabolism of stearic, oleic, linoleic and alpha-linolenic acids in minimal deviation hepatoma 7288 C cells.", "content": "Minimal Deviation Hepatoma 7288 C cells were cultured in confluent layer with labeled stearic, oleic, linoleic and alpha-linolenic acids. The kinetics of incorporation and conversion to higher homologs was studied. The maximum amounts incorporated in nmoles per mg of cellular protein for stearic, oleic, linoleic and alpha-linolenic acids were 39, 115.6, 90 and 230 respectively. alpha-linolenic acid was converted to octadeca-6,9,12,15-tetraenoic acid (18:1), eicosa-11,14,17-trienoic acid (20:3), eicosa-8,11,14,17 and 5,11,14,17-tetraenoic acids (20:4) and eicosa-5,8,11,14,17-pentaenoic acid (20:5), and also to myristic, palmitic, palmitoleic, stearic and oleic acids. By a mathematical approach, the endogenous pool size of alpha-linolenic acid available for conversion to eicosa-5,8,11,14,17-pentaenoic acid, were calculated. Both values decreased when the cells were preincubated with unlabeled alpha-linolenic acid.", "contents": "Incorporation and metabolism of stearic, oleic, linoleic and alpha-linolenic acids in minimal deviation hepatoma 7288 C cells. Minimal Deviation Hepatoma 7288 C cells were cultured in confluent layer with labeled stearic, oleic, linoleic and alpha-linolenic acids. The kinetics of incorporation and conversion to higher homologs was studied. The maximum amounts incorporated in nmoles per mg of cellular protein for stearic, oleic, linoleic and alpha-linolenic acids were 39, 115.6, 90 and 230 respectively. alpha-linolenic acid was converted to octadeca-6,9,12,15-tetraenoic acid (18:1), eicosa-11,14,17-trienoic acid (20:3), eicosa-8,11,14,17 and 5,11,14,17-tetraenoic acids (20:4) and eicosa-5,8,11,14,17-pentaenoic acid (20:5), and also to myristic, palmitic, palmitoleic, stearic and oleic acids. By a mathematical approach, the endogenous pool size of alpha-linolenic acid available for conversion to eicosa-5,8,11,14,17-pentaenoic acid, were calculated. Both values decreased when the cells were preincubated with unlabeled alpha-linolenic acid."}
{"id": "PMID:196186", "title": "An investigation of the stability of messenger RNAs in cell-free, translational systems from uninfected and mengovirus-infected Ehrlich ascites tumor cells.", "content": "The stabilities and translation of Ehrlich ascites tumor cell poly(A)-containing mRNA and mengovirus RNA in fractionated cell-free protein synthesizing systems from uninfected and mengovirus-infected Ehrlich ascites tumor cells were studied. During incubation of the systems about 20% of the input RNA is reduced in size and associated with ribosomes engaged in polypeptide synthesis; the remainder is rapidly degraded by RNases. At the end of active translation, both mRNA and nascent proteins are bound to polysomes which are of the same size as those formed during active protein synthesis. The kinetics of protein synthesis closely follow those of RNA hydrolysis. The stabilities of mengovirus RNA and poly(A)-containing mRNA from Ehrlich ascites tumor cells are the same in both systems.", "contents": "An investigation of the stability of messenger RNAs in cell-free, translational systems from uninfected and mengovirus-infected Ehrlich ascites tumor cells. The stabilities and translation of Ehrlich ascites tumor cell poly(A)-containing mRNA and mengovirus RNA in fractionated cell-free protein synthesizing systems from uninfected and mengovirus-infected Ehrlich ascites tumor cells were studied. During incubation of the systems about 20% of the input RNA is reduced in size and associated with ribosomes engaged in polypeptide synthesis; the remainder is rapidly degraded by RNases. At the end of active translation, both mRNA and nascent proteins are bound to polysomes which are of the same size as those formed during active protein synthesis. The kinetics of protein synthesis closely follow those of RNA hydrolysis. The stabilities of mengovirus RNA and poly(A)-containing mRNA from Ehrlich ascites tumor cells are the same in both systems."}
{"id": "PMID:196187", "title": "[Myoclonic encephalopathy in childhood (author's transl)].", "content": "Two new cases of infantile myoclonic encephalopathy are reported and a survey of literature is given. The disease is characterized by generalised myoclonic jerks in all striated muscles, by cerebellar ataxia and by fast, jerking, mostly conjugated irregular eye movements (opsoclonus). The disease develops mostly during late infancy and early childhood. The pathogenesis is unknown, probably it is caused by immunological reactions to various agents. Treatment with ACTH or corticosteroids leads to rapid remission of the initial neurological symptoms, but it is suggested that therapy does not prevent frequent sequelae of psychomotor retardation and speech distubances. Remarkably, there is the high coincidence of infantile myoclonic encephalopathy and neuroblastoma. Therefore it is necessary to keep in mind the possibility of a causative neuroblastoma in all children with myoclonic encephalopathy and to control repeatly radiological findings and urin-excretion of catecholamines as well as their metabolic products.", "contents": "[Myoclonic encephalopathy in childhood (author's transl)]. Two new cases of infantile myoclonic encephalopathy are reported and a survey of literature is given. The disease is characterized by generalised myoclonic jerks in all striated muscles, by cerebellar ataxia and by fast, jerking, mostly conjugated irregular eye movements (opsoclonus). The disease develops mostly during late infancy and early childhood. The pathogenesis is unknown, probably it is caused by immunological reactions to various agents. Treatment with ACTH or corticosteroids leads to rapid remission of the initial neurological symptoms, but it is suggested that therapy does not prevent frequent sequelae of psychomotor retardation and speech distubances. Remarkably, there is the high coincidence of infantile myoclonic encephalopathy and neuroblastoma. Therefore it is necessary to keep in mind the possibility of a causative neuroblastoma in all children with myoclonic encephalopathy and to control repeatly radiological findings and urin-excretion of catecholamines as well as their metabolic products."}
{"id": "PMID:196188", "title": "[Prognosis of prenatal varicella-zoster-infections in relation to their onset during pregnancy (author's transl)].", "content": "7 children were observed, whose mothers had Varicella-Zoster-Virus-infection. 3 of these children developed postnatal Herpes Zoster without Varicella in their history; 1 child had Varicella in the neonatal period. There are indications that primary infection with Varicella-Zoster-Virus during the first four months of pregnancy may cause deformities in the child; the same during the last five days of pregnancy increases the risk of varicella with a complicated course in the newborn. Independent of the time of infection during pregnancy the prognosis of a secondary Varicella-Zoster-Virus-infection in the mother seems always to be good for the child. Aspects of the child's immunological maturation, still incomplete at birth, are discussed and can help to understand the different prognoses during pregnancy. The importance of serological diagnosis has been emphasized.", "contents": "[Prognosis of prenatal varicella-zoster-infections in relation to their onset during pregnancy (author's transl)]. 7 children were observed, whose mothers had Varicella-Zoster-Virus-infection. 3 of these children developed postnatal Herpes Zoster without Varicella in their history; 1 child had Varicella in the neonatal period. There are indications that primary infection with Varicella-Zoster-Virus during the first four months of pregnancy may cause deformities in the child; the same during the last five days of pregnancy increases the risk of varicella with a complicated course in the newborn. Independent of the time of infection during pregnancy the prognosis of a secondary Varicella-Zoster-Virus-infection in the mother seems always to be good for the child. Aspects of the child's immunological maturation, still incomplete at birth, are discussed and can help to understand the different prognoses during pregnancy. The importance of serological diagnosis has been emphasized."}
{"id": "PMID:196189", "title": "[Examination at the bedside (author's transl)].", "content": "The difficulties of neurological examination techniques are often over-estimated. It is feared that the large number of individual symptoms cannot be disentangled. But if the principles of classification are known, the individual findings can easily be interpreted and evaluated. If several functions are disordered the disturbance must be sought where the tracts or groups of cells serving these functions lie close together. The investigation of motoricity and sensitivity, the testing of reflexes, coordination, cerebral nerves, circulation in the head and the higher cerebral functions are presented in detail. The significance of the simple clinical examination is considerably increased if the individual symptoms can be seen as an integrated whole.", "contents": "[Examination at the bedside (author's transl)]. The difficulties of neurological examination techniques are often over-estimated. It is feared that the large number of individual symptoms cannot be disentangled. But if the principles of classification are known, the individual findings can easily be interpreted and evaluated. If several functions are disordered the disturbance must be sought where the tracts or groups of cells serving these functions lie close together. The investigation of motoricity and sensitivity, the testing of reflexes, coordination, cerebral nerves, circulation in the head and the higher cerebral functions are presented in detail. The significance of the simple clinical examination is considerably increased if the individual symptoms can be seen as an integrated whole."}
{"id": "PMID:196190", "title": "[Guidelines to the therapie of the most important rheumatic diseases (author's transl)].", "content": "Causal therapy of rheumatic diseases is only possible in the few cases of bacterial infection and some arthroses. In the usually etiologically obscure inflammatory forms, however, the considered use of operative, medicinal and physical measures may achieve improvement or long continued remission, even if healing occurs only rarely. Medicinal treatment and the, in principle, equally justified physiotherapy, especially kinesitherapy, are to be planned from the beginning as longterm therapy which demands close cooperation between the fully informed physician and the completely enlightened patient. The high incidence of side effects of the \"basis\" drugs and the often necessary combinations of palliatives with corticosteroids enforces a strict indication and constant critical appraisal of the current treatment.", "contents": "[Guidelines to the therapie of the most important rheumatic diseases (author's transl)]. Causal therapy of rheumatic diseases is only possible in the few cases of bacterial infection and some arthroses. In the usually etiologically obscure inflammatory forms, however, the considered use of operative, medicinal and physical measures may achieve improvement or long continued remission, even if healing occurs only rarely. Medicinal treatment and the, in principle, equally justified physiotherapy, especially kinesitherapy, are to be planned from the beginning as longterm therapy which demands close cooperation between the fully informed physician and the completely enlightened patient. The high incidence of side effects of the \"basis\" drugs and the often necessary combinations of palliatives with corticosteroids enforces a strict indication and constant critical appraisal of the current treatment."}
{"id": "PMID:196194", "title": "Ectopic production of chorionic gonadotropin and its subunits by islet-cell tumors. A specific marker for malignancy.", "content": "We measured human chorionic gonadotropin (hCG) and its subunits in 76 patients with islet-cell tumors. Seventeen of 27 patients with functioning islet-cell carcinomas had elevated plasma levels of hCG or one of its subunits (hCG-alpha and hCG-beta). Secretion was often discordant; the most frequent finding was an elevated level of hCG-alpha alone. In one patient responding to streptozocin, changes in hCG-alpha correlated with the clinical course. Studies of tumor extracts suggested that the markers observed in the circulation were being produced in the tumor itself. In contrast, none of the 43 patients with benign disease or the six patients with nonfunctioning malignant tumors had elevated levels of hCG, hCG-alpha or hCG-beta. These data show that hCG and its subunits are prevalent and specific markers for islet-cell carcinoma, and suggest that ectopic secretion results from malignant derepression of the genome rather than overproduction by an aberrant \"cell rest.\"", "contents": "Ectopic production of chorionic gonadotropin and its subunits by islet-cell tumors. A specific marker for malignancy. We measured human chorionic gonadotropin (hCG) and its subunits in 76 patients with islet-cell tumors. Seventeen of 27 patients with functioning islet-cell carcinomas had elevated plasma levels of hCG or one of its subunits (hCG-alpha and hCG-beta). Secretion was often discordant; the most frequent finding was an elevated level of hCG-alpha alone. In one patient responding to streptozocin, changes in hCG-alpha correlated with the clinical course. Studies of tumor extracts suggested that the markers observed in the circulation were being produced in the tumor itself. In contrast, none of the 43 patients with benign disease or the six patients with nonfunctioning malignant tumors had elevated levels of hCG, hCG-alpha or hCG-beta. These data show that hCG and its subunits are prevalent and specific markers for islet-cell carcinoma, and suggest that ectopic secretion results from malignant derepression of the genome rather than overproduction by an aberrant \"cell rest.\""}
{"id": "PMID:196195", "title": "Estrogen and endometrial carcinoma. An independent pathology review supporting original risk estimate.", "content": "Initial evidence suggested that estrogen therapy increases the risk of endometrial carcinoma. It was then suggested that some studies may have exaggerated the hazard of estrogen therapy by including patients with atypical endometrial hyperplasia among those having endometrial carcinoma. Three internationally recognized pathologists reviewed the histology slides available from the Ziel and Finkle study, which originally reported a risk ratio of 7.6 for estrogen users. At least one of the pathologists concurred with the original diagnosis in all but one case. Furthermore, all pathologists aggreed that 74 per cent (66/89) were correctly diagnosed. In the 66 patients with unanimous diagnosis, 61 per cent (40/66) had used conjugated estrogens, versus 57 per cent (54/94) in the original study. On the basis of 66 patients and 132 matched controls, the revised risk-ratio estimate is 8.1 (with a one-sided 95 per cent lower confidence limit of 4.5), validating the original estimate.", "contents": "Estrogen and endometrial carcinoma. An independent pathology review supporting original risk estimate. Initial evidence suggested that estrogen therapy increases the risk of endometrial carcinoma. It was then suggested that some studies may have exaggerated the hazard of estrogen therapy by including patients with atypical endometrial hyperplasia among those having endometrial carcinoma. Three internationally recognized pathologists reviewed the histology slides available from the Ziel and Finkle study, which originally reported a risk ratio of 7.6 for estrogen users. At least one of the pathologists concurred with the original diagnosis in all but one case. Furthermore, all pathologists aggreed that 74 per cent (66/89) were correctly diagnosed. In the 66 patients with unanimous diagnosis, 61 per cent (40/66) had used conjugated estrogens, versus 57 per cent (54/94) in the original study. On the basis of 66 patients and 132 matched controls, the revised risk-ratio estimate is 8.1 (with a one-sided 95 per cent lower confidence limit of 4.5), validating the original estimate."}
{"id": "PMID:196197", "title": "A cluster of Epstein-Barr-virus-associated American Burkitt's lymphoma.", "content": "We investigated four patients in whom histologically confirmed Burkitt's lymphomas developed during a one-year period. They were young adults living within 50 km of each other in a rural area of Pennsylvania. Two patients were related by marriage, but there was no contact with or between the other two. Although the majority of American Burkitt's lymphomas are not associated with the Epstein-Barr virus, all four patients showed spectra and titers of antibodies to antigens related to that virus that were characteristic of virus-associated Burkitt's lymphoma in Africa. Viral DNA and numerous cells with virus-determined nuclear antigen were found in tumor specimens available from three patients. These cases are unusual, since time-space clustering of Burkitt's lymphoma associated with Epstein-Barr virus has been observed thus far only in Africa.", "contents": "A cluster of Epstein-Barr-virus-associated American Burkitt's lymphoma. We investigated four patients in whom histologically confirmed Burkitt's lymphomas developed during a one-year period. They were young adults living within 50 km of each other in a rural area of Pennsylvania. Two patients were related by marriage, but there was no contact with or between the other two. Although the majority of American Burkitt's lymphomas are not associated with the Epstein-Barr virus, all four patients showed spectra and titers of antibodies to antigens related to that virus that were characteristic of virus-associated Burkitt's lymphoma in Africa. Viral DNA and numerous cells with virus-determined nuclear antigen were found in tumor specimens available from three patients. These cases are unusual, since time-space clustering of Burkitt's lymphoma associated with Epstein-Barr virus has been observed thus far only in Africa."}
{"id": "PMID:196198", "title": "Annual discourse--don't eat the quails.", "content": "Physicians were the first individuals recorded by name in history. Their attempts to define disease influenced fundamentally the cultures and religions of the world. Surgical skills, although highly developed in ancient times, appear to have been less well documented historically than medical disorders. Because of the greater threat to survival that diseases posed, they became incorporated into religious customs. Contagious diseases also influenced greatly the laws, traditions and historical events of the Bible. Leprosy provided a physical example that presumably represented an image of sin, but it probably was no more prevalent as a disease during Biblical times than at present. Many of the Biblical stories assumed to be allegorical may have been founded on medical fact. For example, it appears likely that the quails that poisoned the wandering Jews were contaminated with cyanide.", "contents": "Annual discourse--don't eat the quails. Physicians were the first individuals recorded by name in history. Their attempts to define disease influenced fundamentally the cultures and religions of the world. Surgical skills, although highly developed in ancient times, appear to have been less well documented historically than medical disorders. Because of the greater threat to survival that diseases posed, they became incorporated into religious customs. Contagious diseases also influenced greatly the laws, traditions and historical events of the Bible. Leprosy provided a physical example that presumably represented an image of sin, but it probably was no more prevalent as a disease during Biblical times than at present. Many of the Biblical stories assumed to be allegorical may have been founded on medical fact. For example, it appears likely that the quails that poisoned the wandering Jews were contaminated with cyanide."}
{"id": "PMID:196204", "title": "The location of the polio genome protein in viral RNAs and its implication for RNA synthesis.", "content": "Evidence is presented that a small protein (VPg) is covalently attached to the 5'-terminal oligonucleotide VPg-pU-U-A-A-A-A-C-A-Gp of the polio genome, to nascent strands of the polio replicative intermediate and to poly(U) of minus strands. A model of polio RNA replication is proposed implicating VPg in initiation of RNA symthesis, possibly as primer.", "contents": "The location of the polio genome protein in viral RNAs and its implication for RNA synthesis. Evidence is presented that a small protein (VPg) is covalently attached to the 5'-terminal oligonucleotide VPg-pU-U-A-A-A-A-C-A-Gp of the polio genome, to nascent strands of the polio replicative intermediate and to poly(U) of minus strands. A model of polio RNA replication is proposed implicating VPg in initiation of RNA symthesis, possibly as primer."}
{"id": "PMID:196221", "title": "Experimental studies on vertical infection of mice with Japanese encephalitis virus. II. Effect of inoculation route on placental and fetal infection.", "content": "Studies were made on the effect of the route of inoculation on the establishment of experimental vertical infection of mice with Japanese encephalitis virus. Mice of the three strains, CFW, C3H/He, and C57BL/6, were inoculated with a field strain of the virus by the intravenous, intraperitoneal, or subcutaneous route. An attempt was made on them to recover the virus from the placenta and fetus. As a result, there were differences in rate of plancental and fetal infection among the route of inoculation. It was dependent the establishment of vertical infection. In general, the rates of placental and fetal infection were the highest in the case of intravenous inoculation, the second highest in the case of intraperitoneal inoculation, and the lowest in the case of subcutaneous inoculation, although there were small differences in this tendency among the mouse strains used. The differences in the rates of placental and fetal infection were presumed to be derived not from the difference in the severity of infection of the respective mothers, but from the degree of direct approach of virus to the placenta as one of the factors.", "contents": "Experimental studies on vertical infection of mice with Japanese encephalitis virus. II. Effect of inoculation route on placental and fetal infection. Studies were made on the effect of the route of inoculation on the establishment of experimental vertical infection of mice with Japanese encephalitis virus. Mice of the three strains, CFW, C3H/He, and C57BL/6, were inoculated with a field strain of the virus by the intravenous, intraperitoneal, or subcutaneous route. An attempt was made on them to recover the virus from the placenta and fetus. As a result, there were differences in rate of plancental and fetal infection among the route of inoculation. It was dependent the establishment of vertical infection. In general, the rates of placental and fetal infection were the highest in the case of intravenous inoculation, the second highest in the case of intraperitoneal inoculation, and the lowest in the case of subcutaneous inoculation, although there were small differences in this tendency among the mouse strains used. The differences in the rates of placental and fetal infection were presumed to be derived not from the difference in the severity of infection of the respective mothers, but from the degree of direct approach of virus to the placenta as one of the factors."}
{"id": "PMID:196222", "title": "Antibody estimation by indirect complement fixation test for foot-and-mouth disease in cattle.", "content": "Antibody against foot-and-mouth disease (FMD) virus was measured by the indirect complement fixation (ICF) test. For this test serum samples were collected from cattle experimentally infected with FMD virus of O, A and Asia 1 types, as well as cattle infected in the field. Two types of antigen were used. One was antigen derived from infected lingual epithelial culture prepared by Frenkel's method with each type of the virus. The other was antigen derived from the lingual epithelium of cattle infected by virus inoculation. ICF antibody began to be dectected about 4 5 days after inoculation. It reached a maximum titer 10  14 days after inoculation, remaining at this titer for about a week or two, and then decreased gradually. It was, however, detectable even 63 days after inoculation. The rise and fall of ICF antibody was parallel with that of neutralizing antibody, although that antibody was always lower in titer than this. ICF antibody was detected type-specifically from cattle infected experimentally and naturally. These results indicated that the ICF test was available for the routine serological diagnosis and epizootiological investigation and research.", "contents": "Antibody estimation by indirect complement fixation test for foot-and-mouth disease in cattle. Antibody against foot-and-mouth disease (FMD) virus was measured by the indirect complement fixation (ICF) test. For this test serum samples were collected from cattle experimentally infected with FMD virus of O, A and Asia 1 types, as well as cattle infected in the field. Two types of antigen were used. One was antigen derived from infected lingual epithelial culture prepared by Frenkel's method with each type of the virus. The other was antigen derived from the lingual epithelium of cattle infected by virus inoculation. ICF antibody began to be dectected about 4 5 days after inoculation. It reached a maximum titer 10  14 days after inoculation, remaining at this titer for about a week or two, and then decreased gradually. It was, however, detectable even 63 days after inoculation. The rise and fall of ICF antibody was parallel with that of neutralizing antibody, although that antibody was always lower in titer than this. ICF antibody was detected type-specifically from cattle infected experimentally and naturally. These results indicated that the ICF test was available for the routine serological diagnosis and epizootiological investigation and research."}
{"id": "PMID:196225", "title": "Solid phase radioimmunoassay for cyclic AMP using staphylococcal protein A-antibody adsorbent.", "content": "A radioimmunoassay for cyclic AMP has been developed using protein A containing staphylococci as an immunoabsorbent. Protein A containing heat-killed staphylococci (Cowan I) are coated with rabbit antiserum raised against the 2'-O-succinyl derivative of cyclic AMP coupled to human serum albumin. After washing with a Tween 20 containing buffer, antibody coated staphylococci are diluted with heat-killed staphylococci devoid of protein A (staphylococcus epidermidis) and mixed with [125I]-2'-O-succinyl cyclic AMP tyrosine methyl ester, standards or unknowns. At the end of the incubation, separation of bound and free labelled antigen is achieved by bound and free labelled antigen is achieved by centrifugation. The results are comparable to those obtained with a precipitation assay using polyethylenglycol 6000. Acetylation prior to radioimmunoassay increases sensitivity about 80-fold. 50% depression of zero dose binding occurs at 15--16 femtomoles acetylated cyclic AMP. The crossreactivity with cyclic GMP, ATP, ADP, 5'-AMP and adenosine is extremely low. The present technique is an attractive alternative to the second antibody method or polyethylenglycol precipitation.", "contents": "Solid phase radioimmunoassay for cyclic AMP using staphylococcal protein A-antibody adsorbent. A radioimmunoassay for cyclic AMP has been developed using protein A containing staphylococci as an immunoabsorbent. Protein A containing heat-killed staphylococci (Cowan I) are coated with rabbit antiserum raised against the 2'-O-succinyl derivative of cyclic AMP coupled to human serum albumin. After washing with a Tween 20 containing buffer, antibody coated staphylococci are diluted with heat-killed staphylococci devoid of protein A (staphylococcus epidermidis) and mixed with [125I]-2'-O-succinyl cyclic AMP tyrosine methyl ester, standards or unknowns. At the end of the incubation, separation of bound and free labelled antigen is achieved by bound and free labelled antigen is achieved by centrifugation. The results are comparable to those obtained with a precipitation assay using polyethylenglycol 6000. Acetylation prior to radioimmunoassay increases sensitivity about 80-fold. 50% depression of zero dose binding occurs at 15--16 femtomoles acetylated cyclic AMP. The crossreactivity with cyclic GMP, ATP, ADP, 5'-AMP and adenosine is extremely low. The present technique is an attractive alternative to the second antibody method or polyethylenglycol precipitation."}
{"id": "PMID:196230", "title": "[Case of amyloid polyneuropathy].", "content": "The authors report a case of sporadic secondary amyloidosis with polyneuropathy in a patient aged 50 years. The disease developed during chronic pyelonephritis. The case is described in view of its rare occurrence, diagnostic difficulties and interesting histological findings.", "contents": "[Case of amyloid polyneuropathy]. The authors report a case of sporadic secondary amyloidosis with polyneuropathy in a patient aged 50 years. The disease developed during chronic pyelonephritis. The case is described in view of its rare occurrence, diagnostic difficulties and interesting histological findings."}
{"id": "PMID:196231", "title": "Lack of detectable secretion of ACTH from pituitary homografts of pars intermedia.", "content": "Hypophysectomized rats bearing grafts of the pars intermedia (PI) in the kidney capsule for 20 days did not show adrenal weights significantly different from those of hypophysectomized controls. Plasma corticosterone was undetectable in the grafted rats, even after the injection of lysine-vasopressin or histamine. On the other hand, MSH activity was present in measueable amounts, independent of the drug administered, in the plasma of the grafted rats. These results suggest that PI transplants do not have the ability to release ACTH, even though it has been previously reported that they contain this hormone.", "contents": "Lack of detectable secretion of ACTH from pituitary homografts of pars intermedia. Hypophysectomized rats bearing grafts of the pars intermedia (PI) in the kidney capsule for 20 days did not show adrenal weights significantly different from those of hypophysectomized controls. Plasma corticosterone was undetectable in the grafted rats, even after the injection of lysine-vasopressin or histamine. On the other hand, MSH activity was present in measueable amounts, independent of the drug administered, in the plasma of the grafted rats. These results suggest that PI transplants do not have the ability to release ACTH, even though it has been previously reported that they contain this hormone."}
{"id": "PMID:196232", "title": "Cerebrospinal fluid norepinephrine alterations during electrical stimulation of cerebellar, cerebral surfaces in epileptic patients.", "content": "Lumbar cerebrospinal fluid norepinephrine concentrations were determined by radioenzymatic assay in five epileptic patients receiving double-blind cerebellar stimulation and in three epileptic patients with subdural cerebral surface electrodes. Mean CSF norepinephrine levels were significantly elevated by chronic cerebellar stimulation and significantly depressed after intermittent cerebral cortical stimulation. Lumbar CSF cyclic adenosine monophosphate levels determined by radioimmunoassay were not significantly altered by either cerebellar or cerebral surface stimulation. Our study suggests that (1) electrical stimulation of the anterodorsal cerebellum in man evokes alterations in noradrenergic metabolism. Cerebellar stimulation-induced elevations in norepinephrine may inhibit cerebellar, cerebral, and spinal neuronal activity. In addition, (2) noradrenergic responses to brain surface stimulation may exhibit regional specificity, and (3) noradrenergic alterations evoked by cerebral surface stimulation may not mimic those induced in isolated brain preparations.", "contents": "Cerebrospinal fluid norepinephrine alterations during electrical stimulation of cerebellar, cerebral surfaces in epileptic patients. Lumbar cerebrospinal fluid norepinephrine concentrations were determined by radioenzymatic assay in five epileptic patients receiving double-blind cerebellar stimulation and in three epileptic patients with subdural cerebral surface electrodes. Mean CSF norepinephrine levels were significantly elevated by chronic cerebellar stimulation and significantly depressed after intermittent cerebral cortical stimulation. Lumbar CSF cyclic adenosine monophosphate levels determined by radioimmunoassay were not significantly altered by either cerebellar or cerebral surface stimulation. Our study suggests that (1) electrical stimulation of the anterodorsal cerebellum in man evokes alterations in noradrenergic metabolism. Cerebellar stimulation-induced elevations in norepinephrine may inhibit cerebellar, cerebral, and spinal neuronal activity. In addition, (2) noradrenergic responses to brain surface stimulation may exhibit regional specificity, and (3) noradrenergic alterations evoked by cerebral surface stimulation may not mimic those induced in isolated brain preparations."}
{"id": "PMID:196233", "title": "Distal myopathy: electron microscopic and histochemical studies.", "content": "This report describes the clinical, laboratory, and muscle biopsy histochemical and electron microscopic studies of one inherited and two sporadic cases of distal myopathy. Histopathologic and histochemical studies showed numerous myopathic alterations and no significant evidence of denervation. Electron microscopic studies showed a broad spectrum of nonspecific alterations similar to those in other forms of muscular dystrophy. Autophagic vacuoles were prominent in all cases. The inherited case was characterized by an unusual focal granular degeneration that, ultrastructurally, was composed of homogeneous fine granules devoid of other organelles or myofilamens.", "contents": "Distal myopathy: electron microscopic and histochemical studies. This report describes the clinical, laboratory, and muscle biopsy histochemical and electron microscopic studies of one inherited and two sporadic cases of distal myopathy. Histopathologic and histochemical studies showed numerous myopathic alterations and no significant evidence of denervation. Electron microscopic studies showed a broad spectrum of nonspecific alterations similar to those in other forms of muscular dystrophy. Autophagic vacuoles were prominent in all cases. The inherited case was characterized by an unusual focal granular degeneration that, ultrastructurally, was composed of homogeneous fine granules devoid of other organelles or myofilamens."}
{"id": "PMID:196234", "title": "In vitro-labeled DNA for detecting viral genomes in multiple sclerosis: I. Papovaviruses.", "content": "Papovaviruses appear to be neurotropic and one, JC virus, is implicated as the cause of one type of demyelinating disease, progressive multifocal leukoencephalopathy. To investigate whether human papovaviruses play a role in multiple sclerosis, radioactively labeled DNA from BK virus, human papilloma virus, and simian virus 40 was used as a probe in order to detect related unlabeled DNA sequences in DNA isolated from multiple sclerosis brain and/or spinal cord. Labeled viral probes were denatured and DNA allowed to reassociate in the presence of excess unlabeled DNA from multiple sclerosis tissue or from controls. The reassociation rate of the probe is proportional to the concentration of viral DNA present, and an increase in the reassociation rate of the probe over that of control reactions would indicate the presence of unlabeled viral DNA in multiple sclerosis cellular DNA. However, addition of DNA derived from multiple sclerosis patients did not increase rates of reassociation of viral probes. Known human papovaviruses probably have no role in the pathogenesis of multiple sclerosis.", "contents": "In vitro-labeled DNA for detecting viral genomes in multiple sclerosis: I. Papovaviruses. Papovaviruses appear to be neurotropic and one, JC virus, is implicated as the cause of one type of demyelinating disease, progressive multifocal leukoencephalopathy. To investigate whether human papovaviruses play a role in multiple sclerosis, radioactively labeled DNA from BK virus, human papilloma virus, and simian virus 40 was used as a probe in order to detect related unlabeled DNA sequences in DNA isolated from multiple sclerosis brain and/or spinal cord. Labeled viral probes were denatured and DNA allowed to reassociate in the presence of excess unlabeled DNA from multiple sclerosis tissue or from controls. The reassociation rate of the probe is proportional to the concentration of viral DNA present, and an increase in the reassociation rate of the probe over that of control reactions would indicate the presence of unlabeled viral DNA in multiple sclerosis cellular DNA. However, addition of DNA derived from multiple sclerosis patients did not increase rates of reassociation of viral probes. Known human papovaviruses probably have no role in the pathogenesis of multiple sclerosis."}
{"id": "PMID:196235", "title": "Duchenne dystrophy: ultrastructural localization of the acetylcholine receptor and intracellular microelectrode studies of neuromuscular transmission.", "content": "Despite focal degeneration and simplification of the postsynaptic region in Duchenne dystrophy, the postsynaptic acetylcholine receptor (AChR) is preserved. This is in contrast to myasthenia gravis where similar postsynaptic alterations are invariably associated with a marked decrease in AChR. There is no extrajunctional spread of AChR in Duchenne dystrophy. The amplitude and frequency of miniature end-plate potentials and the number of transmitter quanta released by nerve impulse are normal but the resting membrane potential is lower than normal. The findings indicate that the release and the postsynaptic responsiveness to acetylcholine are intact in Duchenne dystrophy.", "contents": "Duchenne dystrophy: ultrastructural localization of the acetylcholine receptor and intracellular microelectrode studies of neuromuscular transmission. Despite focal degeneration and simplification of the postsynaptic region in Duchenne dystrophy, the postsynaptic acetylcholine receptor (AChR) is preserved. This is in contrast to myasthenia gravis where similar postsynaptic alterations are invariably associated with a marked decrease in AChR. There is no extrajunctional spread of AChR in Duchenne dystrophy. The amplitude and frequency of miniature end-plate potentials and the number of transmitter quanta released by nerve impulse are normal but the resting membrane potential is lower than normal. The findings indicate that the release and the postsynaptic responsiveness to acetylcholine are intact in Duchenne dystrophy."}
{"id": "PMID:196236", "title": "Bone scanning and diagnosis of reflex sympathetic dystrophy secondary to herniated lumbar disks.", "content": "In two cases, reflex sympathetic dystrophy (RSD) was due to herniated intervertebral disk at L4-5. In both cases, bone scanning with technetium 99m pyrophosphate was of value and its use is recommended in diagnosing mild or early cases of RSD. RSD may be the cause of persisting pain after disk surgery.", "contents": "Bone scanning and diagnosis of reflex sympathetic dystrophy secondary to herniated lumbar disks. In two cases, reflex sympathetic dystrophy (RSD) was due to herniated intervertebral disk at L4-5. In both cases, bone scanning with technetium 99m pyrophosphate was of value and its use is recommended in diagnosing mild or early cases of RSD. RSD may be the cause of persisting pain after disk surgery."}
{"id": "PMID:196239", "title": "Nasopharyngeal tumor initially manifested as myofascial pain dysfunction syndrome.", "content": "A patient with facial pain of 1 1/2 years' duration, associated with limitation of opening of the mouth, click, and osteodegenerative changes of the temporomandibular joint, was initially thought to be suffering from a myofascial pain dysfunction syndrome. At first, the patient reacted favorably to muscle exercises and an antidepressive drug, but reduced lacrimation and the development of deafness on the affected side led to re-evaluation and a diagnosis of nasopharyngeal tumor. Biopsy confirmed the presence of an adenocarcinoma of the nasopharynx. The variability of symptoms and the diagnostic problems presented by this tumor are discussed.", "contents": "Nasopharyngeal tumor initially manifested as myofascial pain dysfunction syndrome. A patient with facial pain of 1 1/2 years' duration, associated with limitation of opening of the mouth, click, and osteodegenerative changes of the temporomandibular joint, was initially thought to be suffering from a myofascial pain dysfunction syndrome. At first, the patient reacted favorably to muscle exercises and an antidepressive drug, but reduced lacrimation and the development of deafness on the affected side led to re-evaluation and a diagnosis of nasopharyngeal tumor. Biopsy confirmed the presence of an adenocarcinoma of the nasopharynx. The variability of symptoms and the diagnostic problems presented by this tumor are discussed."}
{"id": "PMID:196248", "title": "Knee maturation as a differentiating sign between congenital rubella and cytomegalovirus infections.", "content": "Knee epiphyseal maturation is retarded in most neonates with congenital rubella infection, whereas neonates with congenital cytomegalovirus infection have relatively normal maturation. Asse-sment of knee maturation is useful in differentiating rubella from cytomegalovirus infection in the neonate.", "contents": "Knee maturation as a differentiating sign between congenital rubella and cytomegalovirus infections. Knee epiphyseal maturation is retarded in most neonates with congenital rubella infection, whereas neonates with congenital cytomegalovirus infection have relatively normal maturation. Asse-sment of knee maturation is useful in differentiating rubella from cytomegalovirus infection in the neonate."}
{"id": "PMID:196247", "title": "Tumors of the chest wall in infants and children.", "content": "Chest wall tumors of children may arise from subcutaneous tissues, the bony thorax, or extrapleural region. Review of experience at our institution and the literature indicates that primary bony tumors are most often malignant; Ewing's sarcoma is the most frequent in this category. Extrapleural tumors are rare but also usually malignant. Clinical and roentgen features of these lesions are discussed.", "contents": "Tumors of the chest wall in infants and children. Chest wall tumors of children may arise from subcutaneous tissues, the bony thorax, or extrapleural region. Review of experience at our institution and the literature indicates that primary bony tumors are most often malignant; Ewing's sarcoma is the most frequent in this category. Extrapleural tumors are rare but also usually malignant. Clinical and roentgen features of these lesions are discussed."}
{"id": "PMID:196249", "title": "Epithelial cells and Von Gierke's disease.", "content": "Epithelial cells and not fibroblasts from human liver and amniotic fluid contain inducible glucose-6-phosphatase (G-6-Pase) activity. The diagnosis of Von Gierke's disease has been made in a patient with hepatomegaly utilizing cultured epithelial cells grown from a liver biopsy. G-6-Pase activity in epithelial cells from this patient could not be induced by dibutyryl cyclic AMP and theophylline. This is the first use of epithelial cells for diagnosis of a metabolic disease. G-6-Pase activity in cloned epithelial cells from amniotic fluid increases 2- to 3-fold after 24-hr exposure to dibutyryl cyclic AMP and theophylline. The prenatal diagnosis of Von Gierke's disease may be possible in a laboratory experienced with these techniques if epithelial cell growth is obtained from amniotic fluid.", "contents": "Epithelial cells and Von Gierke's disease. Epithelial cells and not fibroblasts from human liver and amniotic fluid contain inducible glucose-6-phosphatase (G-6-Pase) activity. The diagnosis of Von Gierke's disease has been made in a patient with hepatomegaly utilizing cultured epithelial cells grown from a liver biopsy. G-6-Pase activity in epithelial cells from this patient could not be induced by dibutyryl cyclic AMP and theophylline. This is the first use of epithelial cells for diagnosis of a metabolic disease. G-6-Pase activity in cloned epithelial cells from amniotic fluid increases 2- to 3-fold after 24-hr exposure to dibutyryl cyclic AMP and theophylline. The prenatal diagnosis of Von Gierke's disease may be possible in a laboratory experienced with these techniques if epithelial cell growth is obtained from amniotic fluid."}
{"id": "PMID:196254", "title": "Spatial summation effects on lingual vibrotactile thresholds.", "content": "Ascending lingual vibrotactile thresholds at 250 Hz were obtained for four groups of normal-speaking adult subjects. Contactor areas were varied for each respective group. Threshold values in microns plotted as a function of the area of vibratory displacement indicated a spatial summation function for the larger contactors (greater than .02 cm2). Findings are discussed in terms of the nature of lingual-tactile mechanoreception and possible implications for neural control mechanisms subserving speech production.", "contents": "Spatial summation effects on lingual vibrotactile thresholds. Ascending lingual vibrotactile thresholds at 250 Hz were obtained for four groups of normal-speaking adult subjects. Contactor areas were varied for each respective group. Threshold values in microns plotted as a function of the area of vibratory displacement indicated a spatial summation function for the larger contactors (greater than .02 cm2). Findings are discussed in terms of the nature of lingual-tactile mechanoreception and possible implications for neural control mechanisms subserving speech production."}
{"id": "PMID:196255", "title": "Changes in rem dream content during the night: implications for a hypothesis about changes in cerebral dominance across rem periods.", "content": "REM dream content was scored for categories suggesting the predominant influence of the left hemisphere, e.g., good ego functioning, verbalization, or the right hemisphere, e.g., music, spatial salience, bizarreness. Data from 5 samples of college men showed consistent evidence of an increase in the prominence of left-, but not right-, related categories from earlier to later REM periods. These data suggest there is an increase in left hemisphere control/dominance across the REM periods during the night. Two sets of predictions based on this hypothesis (using more direct estimates of the hypothesized change) yielded supportive evidence. First, as predicted, there was a positive relation between change in percentage of right eye movement (R%) and (a) temporal position of the REM period and (b) change in left-related categories; greater R% was associated with later REM periods and with more prominent left- (but not right-) hemisphere categories. Second, as predicted, there was a positive relation between the diminution of the ratio of left to right EEG amplitudes (L/R) and (a) temporal position of the REM period and (b) prominence of verbal activity. As expected, this relation was attenuated for those subjects showing a preference for left-handedness. Two possible explanations for the inferred increase in left-hemispheric influence during the night are suggested.", "contents": "Changes in rem dream content during the night: implications for a hypothesis about changes in cerebral dominance across rem periods. REM dream content was scored for categories suggesting the predominant influence of the left hemisphere, e.g., good ego functioning, verbalization, or the right hemisphere, e.g., music, spatial salience, bizarreness. Data from 5 samples of college men showed consistent evidence of an increase in the prominence of left-, but not right-, related categories from earlier to later REM periods. These data suggest there is an increase in left hemisphere control/dominance across the REM periods during the night. Two sets of predictions based on this hypothesis (using more direct estimates of the hypothesized change) yielded supportive evidence. First, as predicted, there was a positive relation between change in percentage of right eye movement (R%) and (a) temporal position of the REM period and (b) change in left-related categories; greater R% was associated with later REM periods and with more prominent left- (but not right-) hemisphere categories. Second, as predicted, there was a positive relation between the diminution of the ratio of left to right EEG amplitudes (L/R) and (a) temporal position of the REM period and (b) prominence of verbal activity. As expected, this relation was attenuated for those subjects showing a preference for left-handedness. Two possible explanations for the inferred increase in left-hemispheric influence during the night are suggested."}
{"id": "PMID:196256", "title": "Intra- and extracellular measurements of frog neuromuscular transmission upon stretch of the muscle at different stimulus frequencies.", "content": "Flexible intracellular micro-electrodes were used to study the effect of changes in muscle length on the end-plate potential in the isolated m. cutaneus pectoris for different frequencies of stimulation (1/60-5Hz). A 20% step-wise increase in muscle length within the physiological range increases the end-plate potential immediately by about 50% (range 0-120%) at all frequencies tested. At stimulus frequencies lower than 1/5 Hz this increase is sustained during a period of 15 min stretch. At 1 Hz, however, the initial increase in the end-plate potential amplitude on the average declines within a few minutes to a steady-state value about 35% higher than the steady-state end-plate potential before stretch. At 5 Hz, the initial amplitude increase is followed by a decline of about 15 min duration and the final amplitude is not increased in comparison with the pre-stretch amplitude. The amplitude of the compound muscle action potential of the gastrocnemius muscle with intact circulation shows a similar time dependent increase upon stretch at different stimulus frequencies. It is concluded that stretch of a frog muscle gives both an immediate and a sustained increase in transmitter release from the nerve terminals during prolonged stimulation at frequencies up to about 5 Hz. This effect of stretch on transmitter release can improve in vivo neuromuscular impulse transmission.", "contents": "Intra- and extracellular measurements of frog neuromuscular transmission upon stretch of the muscle at different stimulus frequencies. Flexible intracellular micro-electrodes were used to study the effect of changes in muscle length on the end-plate potential in the isolated m. cutaneus pectoris for different frequencies of stimulation (1/60-5Hz). A 20% step-wise increase in muscle length within the physiological range increases the end-plate potential immediately by about 50% (range 0-120%) at all frequencies tested. At stimulus frequencies lower than 1/5 Hz this increase is sustained during a period of 15 min stretch. At 1 Hz, however, the initial increase in the end-plate potential amplitude on the average declines within a few minutes to a steady-state value about 35% higher than the steady-state end-plate potential before stretch. At 5 Hz, the initial amplitude increase is followed by a decline of about 15 min duration and the final amplitude is not increased in comparison with the pre-stretch amplitude. The amplitude of the compound muscle action potential of the gastrocnemius muscle with intact circulation shows a similar time dependent increase upon stretch at different stimulus frequencies. It is concluded that stretch of a frog muscle gives both an immediate and a sustained increase in transmitter release from the nerve terminals during prolonged stimulation at frequencies up to about 5 Hz. This effect of stretch on transmitter release can improve in vivo neuromuscular impulse transmission."}
{"id": "PMID:196262", "title": "The use of a standardized teaching program in diabetes education.", "content": "A standardized plan for the patient with diabetes has been implemented in our institution to structure the methods and content of diabetic education. To meet the specific needs of each diabetic patient the plan must be individualized by the primary nurse caring for the patient. The plan requires frequent evaluation and revision to update the content and materials used. In our experience, the use of a standardized program for diabetes education has provided primary nurses with a systematic approach to this important facet of nursing care.", "contents": "The use of a standardized teaching program in diabetes education. A standardized plan for the patient with diabetes has been implemented in our institution to structure the methods and content of diabetic education. To meet the specific needs of each diabetic patient the plan must be individualized by the primary nurse caring for the patient. The plan requires frequent evaluation and revision to update the content and materials used. In our experience, the use of a standardized program for diabetes education has provided primary nurses with a systematic approach to this important facet of nursing care."}
{"id": "PMID:196268", "title": "Two kinds of opiate receptor.", "content": "Studies with azidomorphine derivatives have revealed that some of them, particularly N-cyclopropylmethylnorazidomorphine (CAM), stimulate some opiate receptors, while inhibit the others. The opiate receptors stimulated by CAM are called opiate A receptors, while those antagonized by CAM are called opiate B receptors. Opiate receptors are located at nerve terminals and upon stimulation decrease the release of a neurotransmitter. Opiate A receptors are most probably located at cholinergic nerve terminals, are present in the guinea pig ileum, mouse vas deferens and in the brain. Their stimulation leads to constipation and mental clouding. Opiate B receptors located on adrenergic nerve terminals are present in the cat nictitating membrane and in the brain. Their stimulation produces analgesia, depression of coughing and respiration, catalepsy, and mental clouding.", "contents": "Two kinds of opiate receptor. Studies with azidomorphine derivatives have revealed that some of them, particularly N-cyclopropylmethylnorazidomorphine (CAM), stimulate some opiate receptors, while inhibit the others. The opiate receptors stimulated by CAM are called opiate A receptors, while those antagonized by CAM are called opiate B receptors. Opiate receptors are located at nerve terminals and upon stimulation decrease the release of a neurotransmitter. Opiate A receptors are most probably located at cholinergic nerve terminals, are present in the guinea pig ileum, mouse vas deferens and in the brain. Their stimulation leads to constipation and mental clouding. Opiate B receptors located on adrenergic nerve terminals are present in the cat nictitating membrane and in the brain. Their stimulation produces analgesia, depression of coughing and respiration, catalepsy, and mental clouding."}
{"id": "PMID:196269", "title": "The influence of haloperidol and propranolol on behavior and biochemical changes in the brain of mice treated with LSD.", "content": "The influence of haloperidol and propranolol on aggressiveness, motility exploration and general behavior, and the activity or level of adenylate cyclase, cyclic AMP, and protein kinase in the brain of mice treated with LSD was tested. Haloperidol evidently, and propranolol slightly less, inhibited the behavioral and biochemical changes induced by LSD. It is suggested that psychotomimetic effects of LSD depend on complex action of this compound on aminergic receptors in the central nervous system, and the antipsychotic effectiveness of haloperidol and propranolol is related to interaction of these drugs and LSD with the receptors for monoamines participating in the central neuromediation.", "contents": "The influence of haloperidol and propranolol on behavior and biochemical changes in the brain of mice treated with LSD. The influence of haloperidol and propranolol on aggressiveness, motility exploration and general behavior, and the activity or level of adenylate cyclase, cyclic AMP, and protein kinase in the brain of mice treated with LSD was tested. Haloperidol evidently, and propranolol slightly less, inhibited the behavioral and biochemical changes induced by LSD. It is suggested that psychotomimetic effects of LSD depend on complex action of this compound on aminergic receptors in the central nervous system, and the antipsychotic effectiveness of haloperidol and propranolol is related to interaction of these drugs and LSD with the receptors for monoamines participating in the central neuromediation."}
{"id": "PMID:196273", "title": "The cellular structure of bronchial carcinoids.", "content": "A histological and electronmicroscopic study of bronchial carcinoids indicated that these tumours are argyrophilic in keeping with their occurrence in tissue of embryologically foregut origin. Normal bronchi contain cells that resemble, in their electronmicroscopic content, intestinal Kultschitzky-type cells. Characteristic of the carcinoid cell is the presence of intracellular neurosecretory granules seen on electronmicroscopy despite the apparent absence of argentaffin granules under light microscopy.", "contents": "The cellular structure of bronchial carcinoids. A histological and electronmicroscopic study of bronchial carcinoids indicated that these tumours are argyrophilic in keeping with their occurrence in tissue of embryologically foregut origin. Normal bronchi contain cells that resemble, in their electronmicroscopic content, intestinal Kultschitzky-type cells. Characteristic of the carcinoid cell is the presence of intracellular neurosecretory granules seen on electronmicroscopy despite the apparent absence of argentaffin granules under light microscopy."}
{"id": "PMID:196270", "title": "Catecholamine turnover measurement and ACTH-induced short-term changes of catecholamine levels in individual brain nuclei.", "content": "The effect of acute ACTH treatment on catecholamine content of various brain nuclei was followed by radioenzymatic assay. The hormonal treatment employed affected catecholamine levels only in some hypothalamic nuclei and in the locus coeruleus. Some effects could be detected as rapidly as 10 min after the injection of the hormone. Employing alpha-methyl-para-tyrosine, catecholamine turnover in individual nuclei was estimated, and shown to be quite variable from one area to the other. However, severe limitations seem to exist in vivo, which restrict the feasibility of this approach to basal or chronic situations.", "contents": "Catecholamine turnover measurement and ACTH-induced short-term changes of catecholamine levels in individual brain nuclei. The effect of acute ACTH treatment on catecholamine content of various brain nuclei was followed by radioenzymatic assay. The hormonal treatment employed affected catecholamine levels only in some hypothalamic nuclei and in the locus coeruleus. Some effects could be detected as rapidly as 10 min after the injection of the hormone. Employing alpha-methyl-para-tyrosine, catecholamine turnover in individual nuclei was estimated, and shown to be quite variable from one area to the other. However, severe limitations seem to exist in vivo, which restrict the feasibility of this approach to basal or chronic situations."}
{"id": "PMID:196275", "title": "A non-invasive test for receptor binding applied to nephrogenic diabetes insipidus.", "content": "Studies in animals have determined the importance of specific receptors to the action of many hormones and drugs. In man, a non-invasive external counting technique has been used and absence of receptor function has been demonstrated in a patient with nephrogenic diabetes insipidus using radioactively labelled arginine vasopressin. This is in contrast to the findings in a patient with pituitary diabetes insipidus and a normal control. These results suggest a model for the study of hormone and drug kinetics in man avoiding multiple samplings of biological fluids.", "contents": "A non-invasive test for receptor binding applied to nephrogenic diabetes insipidus. Studies in animals have determined the importance of specific receptors to the action of many hormones and drugs. In man, a non-invasive external counting technique has been used and absence of receptor function has been demonstrated in a patient with nephrogenic diabetes insipidus using radioactively labelled arginine vasopressin. This is in contrast to the findings in a patient with pituitary diabetes insipidus and a normal control. These results suggest a model for the study of hormone and drug kinetics in man avoiding multiple samplings of biological fluids."}
{"id": "PMID:196274", "title": "Recent advances in the identification of hepatitis viruses.", "content": "Resulting directly from the discovery of virus-related antigens, rapid progress has marked the last decade of viral hepatitis research. The hepatitis B virion has been tentatively identified as a DNA virus with an endogenous DNA polymerase, and new serological markers for type B hepatitis have been discovered. Hepatitis A antigen has been identified on a virus-like particle thought to be the hepatitis A virion. Progressively more sophisticated assays for hepatitis antigens and antibodies have been applied to the study of viral hepatitis epidemiology and biochemical-biophysical characterization of the agents. Most recently, knowledge learned from such studies has been exploited to develop a prototype non-infectious but immunogenic hepatitis B vaccine using hepatitis B surface antigen (HBsAg) purified in large quantities from chronic HBsAg carriers. Especially exciting is the prospect, suggested by serological studies of viral hepatitis, that hepatitis viruses besides hepatitis A and B viruses will be identified.", "contents": "Recent advances in the identification of hepatitis viruses. Resulting directly from the discovery of virus-related antigens, rapid progress has marked the last decade of viral hepatitis research. The hepatitis B virion has been tentatively identified as a DNA virus with an endogenous DNA polymerase, and new serological markers for type B hepatitis have been discovered. Hepatitis A antigen has been identified on a virus-like particle thought to be the hepatitis A virion. Progressively more sophisticated assays for hepatitis antigens and antibodies have been applied to the study of viral hepatitis epidemiology and biochemical-biophysical characterization of the agents. Most recently, knowledge learned from such studies has been exploited to develop a prototype non-infectious but immunogenic hepatitis B vaccine using hepatitis B surface antigen (HBsAg) purified in large quantities from chronic HBsAg carriers. Especially exciting is the prospect, suggested by serological studies of viral hepatitis, that hepatitis viruses besides hepatitis A and B viruses will be identified."}
{"id": "PMID:196276", "title": "Hepatoma causing a massive tumour embolus.", "content": "A case of hepatoma is reported, with a typical clinical setting but a most unusual and dramatic final episode. A massive tumour embolus weighing 30 g became arrested on the tricuspid valve, resulting in acute circulatory failure.", "contents": "Hepatoma causing a massive tumour embolus. A case of hepatoma is reported, with a typical clinical setting but a most unusual and dramatic final episode. A massive tumour embolus weighing 30 g became arrested on the tricuspid valve, resulting in acute circulatory failure."}
{"id": "PMID:196277", "title": "[Reference values of cardiac volume in children and adults of the Ivory Coast].", "content": "The cardiac volume in decubitus was measured by Rohrer radiological method in 229 subjects, of which 150 were children of both sexes, aged 4 to 16 and 79 were adult males, 17 to 50 years old. Anthropometric parameters and maximum O2 consumption were also measured. Considering that the size of thorax in Ivory Coast natives is significantly smaller than that of a Caucasian, an eventual influence over the cardiac volume was looked for. Results showed that: -- in the child, the cardiac, volume increased linearly with age: 162 ml at 4 and 680 ml at 16; -- significant positive correlations were found between the cardiac volume, the body-weight andusrface, and the measurements of the thorax; -- when compared to data found in the literature, the cardiac volumes of children and adults of the Ivory Coast in relation with the body weight or surface are lower than the values found in Caucasians; -- children who have been swimming for two years and adults from the  national swimming team have a cardiac volume significantly superior to that of Ivory controls; for these subjects, results are equivalent to those of Caucasians; -- there is a highly significant positive correlation between the cardiac volume and the maximum oxygen consumption. To compare values of cardiac volume in different populations, it is necessary that the groups of subjects be very homogeneous and have a comparable level of activity.", "contents": "[Reference values of cardiac volume in children and adults of the Ivory Coast]. The cardiac volume in decubitus was measured by Rohrer radiological method in 229 subjects, of which 150 were children of both sexes, aged 4 to 16 and 79 were adult males, 17 to 50 years old. Anthropometric parameters and maximum O2 consumption were also measured. Considering that the size of thorax in Ivory Coast natives is significantly smaller than that of a Caucasian, an eventual influence over the cardiac volume was looked for. Results showed that: -- in the child, the cardiac, volume increased linearly with age: 162 ml at 4 and 680 ml at 16; -- significant positive correlations were found between the cardiac volume, the body-weight andusrface, and the measurements of the thorax; -- when compared to data found in the literature, the cardiac volumes of children and adults of the Ivory Coast in relation with the body weight or surface are lower than the values found in Caucasians; -- children who have been swimming for two years and adults from the  national swimming team have a cardiac volume significantly superior to that of Ivory controls; for these subjects, results are equivalent to those of Caucasians; -- there is a highly significant positive correlation between the cardiac volume and the maximum oxygen consumption. To compare values of cardiac volume in different populations, it is necessary that the groups of subjects be very homogeneous and have a comparable level of activity."}
{"id": "PMID:196281", "title": "Neurophysiological aspects of peripheral neuropathies.", "content": "1. Eighty-eight intrafascicular neural recordings were obtained in 10 normal subjects, 5 patients with axonal degeneration and 11 patients with demyelinating neuropathy. 2. Stimulus levels required for perception and fibre activation were higher in neuropathic subjects. Fibres transmitting touch perception had significantly lower conduction velocities in both patient groups, but were very much lower in the group with demyelinating neuropahty than the group with axonal degeneration. Maximum electrical stimulation evoked dispersed fibre responses in the axonal degeneration group and more dispersed, slowly conducting fibre potentials in the demyelinating group. In patients with hypertrophic Charcot-Marie-Tooth disorder, usually only a small group of slowly conducting low amplitude potentials was recorded. 3. Delivery of a train of supramaximal stimuli caused prolongation of latency and dispersion of fibre potentials in all microneurographic recordings. The changes were significantly greater in the axonal neuropathy group than in normals, and recovery was slower. The demyelinating neuropathies showed significantly greater changes than both the normal and the axonal neuropathy groups, and post-tetanic conduction slowing became even more marked after limb temperature was raised. 4. Surface SAP recordings showed normal refractory period in chronic axonal neuropathy but significant latency prolongation occurred in demyelinating neuropathy. 5. It is concluded that both receptor and nerve fibre abnormalities contribute to sensory dysfunction in degenerative and demyelinating neuropathies.", "contents": "Neurophysiological aspects of peripheral neuropathies. 1. Eighty-eight intrafascicular neural recordings were obtained in 10 normal subjects, 5 patients with axonal degeneration and 11 patients with demyelinating neuropathy. 2. Stimulus levels required for perception and fibre activation were higher in neuropathic subjects. Fibres transmitting touch perception had significantly lower conduction velocities in both patient groups, but were very much lower in the group with demyelinating neuropahty than the group with axonal degeneration. Maximum electrical stimulation evoked dispersed fibre responses in the axonal degeneration group and more dispersed, slowly conducting fibre potentials in the demyelinating group. In patients with hypertrophic Charcot-Marie-Tooth disorder, usually only a small group of slowly conducting low amplitude potentials was recorded. 3. Delivery of a train of supramaximal stimuli caused prolongation of latency and dispersion of fibre potentials in all microneurographic recordings. The changes were significantly greater in the axonal neuropathy group than in normals, and recovery was slower. The demyelinating neuropathies showed significantly greater changes than both the normal and the axonal neuropathy groups, and post-tetanic conduction slowing became even more marked after limb temperature was raised. 4. Surface SAP recordings showed normal refractory period in chronic axonal neuropathy but significant latency prolongation occurred in demyelinating neuropathy. 5. It is concluded that both receptor and nerve fibre abnormalities contribute to sensory dysfunction in degenerative and demyelinating neuropathies."}
{"id": "PMID:196280", "title": "[Sensitivity of thyrotoxic heart to adrenergic influences].", "content": "Sensitivity of the cardiovascular system of patients suffering from thyrotoxicosis to exogenous adrenaline was studied. In difference from healthy persons, a single injection of 1 ml of 0.1% adrenaline solution to patients with thyrotoxicosis of moderate severity caused a significant elevation of the arterial pressure, frequency of cardiac contractions, systolic and minute output, myocardiac inotropism indices. An increased inderal reactivity was noted in these patients. Thus, greater sensitivity to adrenergic actions and to beta-adrenoblock was observed in conditions of an excess of thyroid hormones. A coincident administration of adrenaline and inderal balanced the positive chronoinotropic effect of the former, but failed to prevent the hypertensive effect of adrenaline.", "contents": "[Sensitivity of thyrotoxic heart to adrenergic influences]. Sensitivity of the cardiovascular system of patients suffering from thyrotoxicosis to exogenous adrenaline was studied. In difference from healthy persons, a single injection of 1 ml of 0.1% adrenaline solution to patients with thyrotoxicosis of moderate severity caused a significant elevation of the arterial pressure, frequency of cardiac contractions, systolic and minute output, myocardiac inotropism indices. An increased inderal reactivity was noted in these patients. Thus, greater sensitivity to adrenergic actions and to beta-adrenoblock was observed in conditions of an excess of thyroid hormones. A coincident administration of adrenaline and inderal balanced the positive chronoinotropic effect of the former, but failed to prevent the hypertensive effect of adrenaline."}
{"id": "PMID:196279", "title": "[Effect of enteral administration of sodium ribonucleate on the synthesis of amino acyl t RNA in the liver and skeletal muscles of rabbits in experimental hypercorticism].", "content": "Daily, for 14 days, rabbits of one group were injected with corticotropin, i.e. ACTH-zinc-phosphate (10 units/kg), whereas rabbits of another group were given (in addition) sodium ribonucleate (40 mg/kg) through a tube into the stomach. Formation of lysyl-tRNA, leucyl-tRNA, and alanyl-tRNA in the liver and the skeletal muscles proved to be significantly greater in the animals which received ACTH together with sodium ribonucleate, as compared to that in the animals given the hormone alone. Hyperglycemia, hepatomegaly, and emaciation were less pronounced in the animals given both the preparations.", "contents": "[Effect of enteral administration of sodium ribonucleate on the synthesis of amino acyl t RNA in the liver and skeletal muscles of rabbits in experimental hypercorticism]. Daily, for 14 days, rabbits of one group were injected with corticotropin, i.e. ACTH-zinc-phosphate (10 units/kg), whereas rabbits of another group were given (in addition) sodium ribonucleate (40 mg/kg) through a tube into the stomach. Formation of lysyl-tRNA, leucyl-tRNA, and alanyl-tRNA in the liver and the skeletal muscles proved to be significantly greater in the animals which received ACTH together with sodium ribonucleate, as compared to that in the animals given the hormone alone. Hyperglycemia, hepatomegaly, and emaciation were less pronounced in the animals given both the preparations."}
{"id": "PMID:196283", "title": "Heat capacity and entropy changes in processes involving proteins.", "content": "Six possible sources of the large heat capacity and entropy changes frequently observed for processes involving proteins are identified. Of these the conformational, hydrophobic, and vibrational effects seem likely to be of greatest importance. A method is proposed for estimating the magnitudes of the hydrophobic and vibrational contributions. Application of this method to several protein processes appears to achieve significant clarification of previously confusing and apparently contradictory data.", "contents": "Heat capacity and entropy changes in processes involving proteins. Six possible sources of the large heat capacity and entropy changes frequently observed for processes involving proteins are identified. Of these the conformational, hydrophobic, and vibrational effects seem likely to be of greatest importance. A method is proposed for estimating the magnitudes of the hydrophobic and vibrational contributions. Application of this method to several protein processes appears to achieve significant clarification of previously confusing and apparently contradictory data."}
{"id": "PMID:196284", "title": "Inhibition of DNA synthesis in cultures of 3T3 cells by isolated surface membranes.", "content": "When added to a sparse culture of 3T3 cells, a surface membrane-enriched fraction from 3T3 cells inhibited the rate of DNA synthesis in a time- and concentration-dependent manner. The membrane preparation had no effect on the rate of DNA synthesis of simian virus 40-transformed 3T3 cells. A similar membrane preparation from transformed cells had a lesser inhibitory effect on 3T3 cells and no effect on transformed cells. The inhibition by membranes was reversible. The data suggest that, when added to growing 3T3 cells, 3T3 surface membranes can mimic the effect of increasing cell density on DNA synthesis.", "contents": "Inhibition of DNA synthesis in cultures of 3T3 cells by isolated surface membranes. When added to a sparse culture of 3T3 cells, a surface membrane-enriched fraction from 3T3 cells inhibited the rate of DNA synthesis in a time- and concentration-dependent manner. The membrane preparation had no effect on the rate of DNA synthesis of simian virus 40-transformed 3T3 cells. A similar membrane preparation from transformed cells had a lesser inhibitory effect on 3T3 cells and no effect on transformed cells. The inhibition by membranes was reversible. The data suggest that, when added to growing 3T3 cells, 3T3 surface membranes can mimic the effect of increasing cell density on DNA synthesis."}
{"id": "PMID:196285", "title": "Characterization of a rat liver factor that inhibits initiation of protein synthesis in rabbit reticulocyte lysates.", "content": "Protein synthesis in rabbit reticulocytes and their lysates is regulated by heme. In heme-deficient reticulocyte lysates, protein synthesis proceeds at the initial rate for several minutes and then declines abruptly. Inhibition of protein synthesis is due to the activation of a heme-regulated translational inhibitor (HRI) which blocks the initiation of protein synthesis. Addition of the isolated HRI to hemin-supplemented lysates causes inhibition of initiation similar to that observed in heme-deficiency. HRI has been shown to be a protein kinase that specifically phosphorylates the Met-tRNA(f) binding factor (eIF-2). We have isolated an inhibitor (LI) of protein chain initiation from rat liver which displays properties similar to those of HRI: (i) the chromatographic behavior of LI on DEAE-Sephadex, DEAE-cellulose, and phosphocellulose is similar to that of HRI; (ii) both LI and HRI inhibit protein chain initiation in rabbit reticulocyte lysates with the same kinetics of inhibition-i.e., an initial period of synthesis for several minutes at the control rate followed by an abrupt decline in the rate of initiation; (iii) both inhibitions are prevented or reversed by eIF-2; (iv) GTP (2 mM) prevents, and ATP (2 mM) potentiates, the inhibition of protein synthesis induced by either inhibitor; (v) LI is associated with a protein kinase that also phosphorylates the 38,000-dalton subunit of elF-2. These findings indicate that a mechanism for the regulation of protein synthesis similar to that found in rabbit reticulocytes may be present in rat liver.", "contents": "Characterization of a rat liver factor that inhibits initiation of protein synthesis in rabbit reticulocyte lysates. Protein synthesis in rabbit reticulocytes and their lysates is regulated by heme. In heme-deficient reticulocyte lysates, protein synthesis proceeds at the initial rate for several minutes and then declines abruptly. Inhibition of protein synthesis is due to the activation of a heme-regulated translational inhibitor (HRI) which blocks the initiation of protein synthesis. Addition of the isolated HRI to hemin-supplemented lysates causes inhibition of initiation similar to that observed in heme-deficiency. HRI has been shown to be a protein kinase that specifically phosphorylates the Met-tRNA(f) binding factor (eIF-2). We have isolated an inhibitor (LI) of protein chain initiation from rat liver which displays properties similar to those of HRI: (i) the chromatographic behavior of LI on DEAE-Sephadex, DEAE-cellulose, and phosphocellulose is similar to that of HRI; (ii) both LI and HRI inhibit protein chain initiation in rabbit reticulocyte lysates with the same kinetics of inhibition-i.e., an initial period of synthesis for several minutes at the control rate followed by an abrupt decline in the rate of initiation; (iii) both inhibitions are prevented or reversed by eIF-2; (iv) GTP (2 mM) prevents, and ATP (2 mM) potentiates, the inhibition of protein synthesis induced by either inhibitor; (v) LI is associated with a protein kinase that also phosphorylates the 38,000-dalton subunit of elF-2. These findings indicate that a mechanism for the regulation of protein synthesis similar to that found in rabbit reticulocytes may be present in rat liver."}
{"id": "PMID:196286", "title": "Isolation of amino acid activating subunit--pantetheine protein complexes: their role in chain elongation in tyrocidine synthesis.", "content": "Dissociation of the multienzymes of tyrocidine synthesis by prolonged incubation of crude extracts of Bacillus brevis (Dubos strain, ATCC 8185) has yielded, on Sephadex G-100 chromatography, two fractions of amino acid activating subunits, a larger one of 70,000 daltons and a smaller one of 90,000 daltons; the latter was a complex consisting of the 70,000 dalton subunit and the pantetheine-carrying protein of about 20,000 daltons. When it dissociated, the intermediate enzyme, which activates three amino acids, contained two-thirds of the subunits in the 70,000 dalton and one-third in the 90,000 dalton fraction; the heavy enzyme, which activates six amino acids, contained five-sixths of the subunits in the former fraction and one-sixth in the latter. Both fractions showed ATP-PP(i) exchange with all amino acids that are activated by the respective polyenzymes. With proline as an example, the 70,000 dalton subunit exhibited a single low-affinity binding site, which should correspond to the peripheral thiol acceptor site, whereas the 90,000 dalton subunit showed both a low-affinity binding site and an additional high-affinity site for proline; the high-affinity site is attributed to the pantetheine present on the pantetheine-carrying protein, and suggests that amino acids are translocated from the peripheral SH to the pantetheine-carrying moiety during chain elongation. This was confirmed by the observation that the 90,000 dalton complex, when incubated with the light enzyme in the presence of phenylalanine and proline, produced DPhe-Pro dipeptide that cyclized into DPhe-Pro diketopiperazine, but the 70,000 dalton activating subunit, when similarly incubated, did not. After subunit dissociation, however, no further elongation occurred after the transfer from phenylalanine to proline.", "contents": "Isolation of amino acid activating subunit--pantetheine protein complexes: their role in chain elongation in tyrocidine synthesis. Dissociation of the multienzymes of tyrocidine synthesis by prolonged incubation of crude extracts of Bacillus brevis (Dubos strain, ATCC 8185) has yielded, on Sephadex G-100 chromatography, two fractions of amino acid activating subunits, a larger one of 70,000 daltons and a smaller one of 90,000 daltons; the latter was a complex consisting of the 70,000 dalton subunit and the pantetheine-carrying protein of about 20,000 daltons. When it dissociated, the intermediate enzyme, which activates three amino acids, contained two-thirds of the subunits in the 70,000 dalton and one-third in the 90,000 dalton fraction; the heavy enzyme, which activates six amino acids, contained five-sixths of the subunits in the former fraction and one-sixth in the latter. Both fractions showed ATP-PP(i) exchange with all amino acids that are activated by the respective polyenzymes. With proline as an example, the 70,000 dalton subunit exhibited a single low-affinity binding site, which should correspond to the peripheral thiol acceptor site, whereas the 90,000 dalton subunit showed both a low-affinity binding site and an additional high-affinity site for proline; the high-affinity site is attributed to the pantetheine present on the pantetheine-carrying protein, and suggests that amino acids are translocated from the peripheral SH to the pantetheine-carrying moiety during chain elongation. This was confirmed by the observation that the 90,000 dalton complex, when incubated with the light enzyme in the presence of phenylalanine and proline, produced DPhe-Pro dipeptide that cyclized into DPhe-Pro diketopiperazine, but the 70,000 dalton activating subunit, when similarly incubated, did not. After subunit dissociation, however, no further elongation occurred after the transfer from phenylalanine to proline."}
{"id": "PMID:196287", "title": "3':5'-cyclic AMP-dependent 3':5'-cyclic GMP accumulation in Dictyostelium discoideum.", "content": "Suspensions of 3':5'-cyclic AMP (cAMP)-sensitive cells of Dictyostelium discoideum responded to a cAMP pulse with increased 3':5'-cyclic GMP (cGMP) levels. Under the assay conditions used (2 x 10(8) cells per ml in 10 mM phosphate buffer, pH 6.0) cAMP (5 x 10(-8) M final concentration) increased cGMP levels from 1 pmol per 10(7) cells to 7 pmol per 10(7) cells in 10 sec and basal levels were recovered in 20-25 sec. cGMP accumulation did not occur when cells were in the cAMP-insensitive stage. cAMP-sensitive cells responded with increased cGMP levels when triggered by 5 x 10(-8) M 5'-CH(2)-cAMP or 10(-5) M adenosine-5'-methylmonophosphate (5'-AMPMe) but not after addition of 5 x 10(-8) M 3':5'-cyclic IMP (cIMP) or 5 x 10(-8) M 5'-AMP. As agonists of cAMP, 5'-CH(2)-cAMP and 5'-AMPMe have, respectively, more than 10% and 1% the chemotactic activity of cAMP, while cIMP has 0.01% the activity of cAMP and 5'-AMP is inactive up to a concentration of 10(-3) M. cAMP-mediated cGMP formation was dependent upon cAMP concentration, with a half-maximal cAMP concentration of about 10(-8) M. This cAMP concentration agrees closely with that necessary for half-maximal receptor occupation. cAMP-mediated cGMP formation was independent of the presence of extracellular Ca(2+); cell aggregation and chemotaxis were also independent of the presence of external Ca(2+). Therefore, cAMP action does not depend on stimulation of the Ca(2+) influx. cAMP was found to mediate desensitization of cAMP-dependent cGMP formation. Addition of 5 x 10(-8) M cAMP to sensitive cells induced a desensitization period that lasted 1-5 min. Desensitization was dependent on the cAMP concentration. Finally, we propose that the translation of a chemotactic signal from the cell surface to pseudopod formation in Dictyostelium involves changes in the levels of cGMP.", "contents": "3':5'-cyclic AMP-dependent 3':5'-cyclic GMP accumulation in Dictyostelium discoideum. Suspensions of 3':5'-cyclic AMP (cAMP)-sensitive cells of Dictyostelium discoideum responded to a cAMP pulse with increased 3':5'-cyclic GMP (cGMP) levels. Under the assay conditions used (2 x 10(8) cells per ml in 10 mM phosphate buffer, pH 6.0) cAMP (5 x 10(-8) M final concentration) increased cGMP levels from 1 pmol per 10(7) cells to 7 pmol per 10(7) cells in 10 sec and basal levels were recovered in 20-25 sec. cGMP accumulation did not occur when cells were in the cAMP-insensitive stage. cAMP-sensitive cells responded with increased cGMP levels when triggered by 5 x 10(-8) M 5'-CH(2)-cAMP or 10(-5) M adenosine-5'-methylmonophosphate (5'-AMPMe) but not after addition of 5 x 10(-8) M 3':5'-cyclic IMP (cIMP) or 5 x 10(-8) M 5'-AMP. As agonists of cAMP, 5'-CH(2)-cAMP and 5'-AMPMe have, respectively, more than 10% and 1% the chemotactic activity of cAMP, while cIMP has 0.01% the activity of cAMP and 5'-AMP is inactive up to a concentration of 10(-3) M. cAMP-mediated cGMP formation was dependent upon cAMP concentration, with a half-maximal cAMP concentration of about 10(-8) M. This cAMP concentration agrees closely with that necessary for half-maximal receptor occupation. cAMP-mediated cGMP formation was independent of the presence of extracellular Ca(2+); cell aggregation and chemotaxis were also independent of the presence of external Ca(2+). Therefore, cAMP action does not depend on stimulation of the Ca(2+) influx. cAMP was found to mediate desensitization of cAMP-dependent cGMP formation. Addition of 5 x 10(-8) M cAMP to sensitive cells induced a desensitization period that lasted 1-5 min. Desensitization was dependent on the cAMP concentration. Finally, we propose that the translation of a chemotactic signal from the cell surface to pseudopod formation in Dictyostelium involves changes in the levels of cGMP."}
{"id": "PMID:196288", "title": "Effects of thyrotropin on the thyroid cell membrane: hyperpolarization induced by hormone-receptor interaction.", "content": "Cultured thyroid cells accumulate the lipophilic cation triphenylmethylphosphonium, indicating that there is an electrical potential (interior negative) across the plasma membrane. Thyrotropin stimulates the uptake of the lipophilic cation 3-fold, and the proton conductor carbonylcyanide-m-chlorophenylhydrazone causes efflux of triphenylmethylphosphonium accumulated in the presence or absence of thyrotropin. The stimulatory effect of thyrotropin on triphenylmethylphosphonium accumulation is not mimicked by human chorionic gonadotropin, a glycoprotein hormone with a similar structure whose target organ is not the thyroid, and the effect is abolished if the thyrotropin-receptor activity of the cells is destroyed by treatment with trypsin. Analogous effects are observed with thyroid plasma membrane vesicles which are essentially devoid of mitochondrial and soluble enzyme activities. Triphenylmethylphosphonium uptake and stimulation by thyrotropin occurs when NaCl, KCl, or Tris.HCl concentration gradients are artifically imposed across the vesicle membrane ([salt](out) > [salt](in)). It seems likely, therefore, that triphenylmethylphosphonium uptake is driven by a chloride diffusion potential (interior negative) and that thyrotropin either increases the permeability of the membrane to anions or decreases its permeability to cations. Thyrotropin-stimulated triphenylmethylphosphonium uptake in the vesicle preparations reaches a quasi steady-state within 3 min; in contrast, thyrotropin-stimulated adenylate cyclase activity is negligible during this period of time, becomes measurable after about 4 min, and is optimal after 12-15 min. Thus, a primary mode of action of thyrotropin on the thyroid cell may be an alteration in the electrical potential across the plasma membrane. The relevance of this observation to the mechanism of action of other glycoprotein hormones, certain bacterial toxins, and interferon is discussed.", "contents": "Effects of thyrotropin on the thyroid cell membrane: hyperpolarization induced by hormone-receptor interaction. Cultured thyroid cells accumulate the lipophilic cation triphenylmethylphosphonium, indicating that there is an electrical potential (interior negative) across the plasma membrane. Thyrotropin stimulates the uptake of the lipophilic cation 3-fold, and the proton conductor carbonylcyanide-m-chlorophenylhydrazone causes efflux of triphenylmethylphosphonium accumulated in the presence or absence of thyrotropin. The stimulatory effect of thyrotropin on triphenylmethylphosphonium accumulation is not mimicked by human chorionic gonadotropin, a glycoprotein hormone with a similar structure whose target organ is not the thyroid, and the effect is abolished if the thyrotropin-receptor activity of the cells is destroyed by treatment with trypsin. Analogous effects are observed with thyroid plasma membrane vesicles which are essentially devoid of mitochondrial and soluble enzyme activities. Triphenylmethylphosphonium uptake and stimulation by thyrotropin occurs when NaCl, KCl, or Tris.HCl concentration gradients are artifically imposed across the vesicle membrane ([salt](out) > [salt](in)). It seems likely, therefore, that triphenylmethylphosphonium uptake is driven by a chloride diffusion potential (interior negative) and that thyrotropin either increases the permeability of the membrane to anions or decreases its permeability to cations. Thyrotropin-stimulated triphenylmethylphosphonium uptake in the vesicle preparations reaches a quasi steady-state within 3 min; in contrast, thyrotropin-stimulated adenylate cyclase activity is negligible during this period of time, becomes measurable after about 4 min, and is optimal after 12-15 min. Thus, a primary mode of action of thyrotropin on the thyroid cell may be an alteration in the electrical potential across the plasma membrane. The relevance of this observation to the mechanism of action of other glycoprotein hormones, certain bacterial toxins, and interferon is discussed."}
{"id": "PMID:196289", "title": "Degradation of cellular mRNA during infection by herpes simplex virus.", "content": "The fate of preexisting mRNA sequences was examined after infection by herpes simplex virus. Murine erythroid cells transformed by Friend leukemia virus were used as the host. Such cells, when exposed to 2% dimethyl sulfoxide, produce large amounts of globin and globin mRNA. The protein and its mRNA are easily recognized at 4 days by electrophoresis in high percentage acrylamide gels and by hybridization to cDNA, respectively. Herpes simplex virus replicates in these cells. By 2 hr after infection the rate of protein synthesis decreases to 30% of the level in mock-infected cells and only 49+/-8% (SEM) of the globin mRNA sequences present prior to infection could be detected by hybridization to cDNA. At 4 hr after infection, when the rate of protein synthesis in infected cells is at a maximum, only about 15% of the globin mRNA sequences remained. Control experiments support the hypothesis that globin mRNA sequences are degraded after infection by herpes simplex virus.", "contents": "Degradation of cellular mRNA during infection by herpes simplex virus. The fate of preexisting mRNA sequences was examined after infection by herpes simplex virus. Murine erythroid cells transformed by Friend leukemia virus were used as the host. Such cells, when exposed to 2% dimethyl sulfoxide, produce large amounts of globin and globin mRNA. The protein and its mRNA are easily recognized at 4 days by electrophoresis in high percentage acrylamide gels and by hybridization to cDNA, respectively. Herpes simplex virus replicates in these cells. By 2 hr after infection the rate of protein synthesis decreases to 30% of the level in mock-infected cells and only 49+/-8% (SEM) of the globin mRNA sequences present prior to infection could be detected by hybridization to cDNA. At 4 hr after infection, when the rate of protein synthesis in infected cells is at a maximum, only about 15% of the globin mRNA sequences remained. Control experiments support the hypothesis that globin mRNA sequences are degraded after infection by herpes simplex virus."}
{"id": "PMID:196290", "title": "Fidelity of synthesis of preribosomal RNA in isolated nucleoli and nucleolar chromatin.", "content": "Comparisons were made of the T1 ribonuclease digests of 32P-labeled nucleolar 45S RNA of intact Novikoff hepatoma cells and the RNA synthesized in vitro by isolated nucleoli. Approximately 200 oligonucleotide spots were found in the two-dimensional chromatogram of 45S nucleolar RNA labeled in vivo, which includes fragments of 18S and 28S rRNA and nonconserved spacer regions; four spots containing 2'-O-methyl nucleotides were not found in the corresponding pattern of RNA labeled in vitro. This high degree of fidelity was retained in the patterns of spots from the RNA produced with nucleolar chromatin as template. This specific expression of rDNA was lost when the nucleolar chromatin was completely deproteinized. Specific spots found in the control patterns were absent and many nonspecific oligonucleotides were found to be labeled. A similar nonspecific chromatogram pattern was found when nucleolar chromatin was transcribed with RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) of Escherichia coli. These results show that specificity of genetic expression in vitro of isolated chromatin of eukaryotic systems is dependent on the chromatin-associated proteins and the type of RNA polymerase present.", "contents": "Fidelity of synthesis of preribosomal RNA in isolated nucleoli and nucleolar chromatin. Comparisons were made of the T1 ribonuclease digests of 32P-labeled nucleolar 45S RNA of intact Novikoff hepatoma cells and the RNA synthesized in vitro by isolated nucleoli. Approximately 200 oligonucleotide spots were found in the two-dimensional chromatogram of 45S nucleolar RNA labeled in vivo, which includes fragments of 18S and 28S rRNA and nonconserved spacer regions; four spots containing 2'-O-methyl nucleotides were not found in the corresponding pattern of RNA labeled in vitro. This high degree of fidelity was retained in the patterns of spots from the RNA produced with nucleolar chromatin as template. This specific expression of rDNA was lost when the nucleolar chromatin was completely deproteinized. Specific spots found in the control patterns were absent and many nonspecific oligonucleotides were found to be labeled. A similar nonspecific chromatogram pattern was found when nucleolar chromatin was transcribed with RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) of Escherichia coli. These results show that specificity of genetic expression in vitro of isolated chromatin of eukaryotic systems is dependent on the chromatin-associated proteins and the type of RNA polymerase present."}
{"id": "PMID:196291", "title": "Transformation by simian virus 40 induces virus-specific, related antigens in the surface membrane and nuclear envelope.", "content": "Nucleus- and mitochondrion-free membranes from hamster lymphocytes transformed by simian virus 40 (SV40), GD248 cells, cause guinea pigs to produce immune sera that reveal the presence in GD248 plasma membranes and mitochondria of two types of glycoprotein that are not detected in membranes of normal lymphocytes [Schmidt-Ullrich, R., Thompson, W. S. & Wallach, D. F. H. (1977) Proc. Natl. Acad. Sci. USA 74, 643-647]. Indirect immune fluorescence of living, SV40-transformed T19 hamster reticulum cells, Balb/c 3T3 mouse fibroblasts, and W18 VA2 human fibroblasts, using the antisera against GD248 membrane, at 4 degrees produced a distinct cell surface fluorescence; however, above 20 degrees , staining at the nuclear perimeter, the SV40 U-antigen reaction, becomes equally prominent. In SV40-transformed cells that had been fixed in cold acetone, as well as in purified GD248 nuclei, thermostable U-antigen staining is dramatic, but there is no reaction for nuclear T-antigen. Rabbit antisera against T19 cells gave immunofluorescence reactions equivalent to those obtained with the antisera against GD248 cells. Normal guinea pig or rabbit sera and cells that had not been transformed by SV40 gave no reaction. Our sera from tumor-bearing hamsters gave only nuclear T-antigen fluorescence. The results indicate the presence of related, SV40-specific antigens in the surface membranes, nuclear envelope, and possibly other intracellular organelles of SV40-transformed cells.", "contents": "Transformation by simian virus 40 induces virus-specific, related antigens in the surface membrane and nuclear envelope. Nucleus- and mitochondrion-free membranes from hamster lymphocytes transformed by simian virus 40 (SV40), GD248 cells, cause guinea pigs to produce immune sera that reveal the presence in GD248 plasma membranes and mitochondria of two types of glycoprotein that are not detected in membranes of normal lymphocytes [Schmidt-Ullrich, R., Thompson, W. S. & Wallach, D. F. H. (1977) Proc. Natl. Acad. Sci. USA 74, 643-647]. Indirect immune fluorescence of living, SV40-transformed T19 hamster reticulum cells, Balb/c 3T3 mouse fibroblasts, and W18 VA2 human fibroblasts, using the antisera against GD248 membrane, at 4 degrees produced a distinct cell surface fluorescence; however, above 20 degrees , staining at the nuclear perimeter, the SV40 U-antigen reaction, becomes equally prominent. In SV40-transformed cells that had been fixed in cold acetone, as well as in purified GD248 nuclei, thermostable U-antigen staining is dramatic, but there is no reaction for nuclear T-antigen. Rabbit antisera against T19 cells gave immunofluorescence reactions equivalent to those obtained with the antisera against GD248 cells. Normal guinea pig or rabbit sera and cells that had not been transformed by SV40 gave no reaction. Our sera from tumor-bearing hamsters gave only nuclear T-antigen fluorescence. The results indicate the presence of related, SV40-specific antigens in the surface membranes, nuclear envelope, and possibly other intracellular organelles of SV40-transformed cells."}
{"id": "PMID:196292", "title": "The intestine as a source of apolipoprotein A1.", "content": "The major apoprotein of rat mesenteric lymph chylomicrons has been isolated and characterized and shown to be identical to apoprotein A1 (apo A1) isolated from serum high density lipoprotein (HDL). During intestinal lipid absorption, active synthesis of apo A1 was demonstrated by radioactive amino acid incorporation into lymph chylomicron A1 as well as lymph HDL. Immunofluorescence studies of intestinal epithelium demonstrated a marked increase in apo A1 fluorescence, confirming an active synthesis of this apoprotein during lipid absorption. Quantitative immunoelectrophoretic methods were used to measure apo A1 in lymph and peripheral blood during various conditions designed to estimate the quantitative importance of intestinal apo A1 to the levels of circulating lipoproteins. During lipid feeding there was an increase in lymph apo A1 that was associated with lymph lipoproteins (50%) of density less than 1.006 g/ml whereas in basal lymph most apo A1 (85%) was in the lipoproteins of density greater than 1.006 g/ml. Lipid feeding in animals without lymph fistulas resulted in a significant increase in serum apo A1 levels; biliary diversion, designed to eliminate intestinal lipoproteins of density less than 1.006 g/ml, resulted in a significant decrease in serum apo A1 levels. These studies demonstrate that the intestine actively synthesizes apo A1 and is a significant source of this apoprotein for circulating lipoproteins.", "contents": "The intestine as a source of apolipoprotein A1. The major apoprotein of rat mesenteric lymph chylomicrons has been isolated and characterized and shown to be identical to apoprotein A1 (apo A1) isolated from serum high density lipoprotein (HDL). During intestinal lipid absorption, active synthesis of apo A1 was demonstrated by radioactive amino acid incorporation into lymph chylomicron A1 as well as lymph HDL. Immunofluorescence studies of intestinal epithelium demonstrated a marked increase in apo A1 fluorescence, confirming an active synthesis of this apoprotein during lipid absorption. Quantitative immunoelectrophoretic methods were used to measure apo A1 in lymph and peripheral blood during various conditions designed to estimate the quantitative importance of intestinal apo A1 to the levels of circulating lipoproteins. During lipid feeding there was an increase in lymph apo A1 that was associated with lymph lipoproteins (50%) of density less than 1.006 g/ml whereas in basal lymph most apo A1 (85%) was in the lipoproteins of density greater than 1.006 g/ml. Lipid feeding in animals without lymph fistulas resulted in a significant increase in serum apo A1 levels; biliary diversion, designed to eliminate intestinal lipoproteins of density less than 1.006 g/ml, resulted in a significant decrease in serum apo A1 levels. These studies demonstrate that the intestine actively synthesizes apo A1 and is a significant source of this apoprotein for circulating lipoproteins."}
{"id": "PMID:196293", "title": "Enhanced oncogenic behavior of human and mouse cells after cellular hybridization with Burkitt tumor cells.", "content": "Studies were made of the expression of the Epstein-Barr virus (EBV) in somatic hybrids of Burkitt tumor cells and human or mouse cells to determine whether EBV genetic information associated with the capacity to transform leukocytes of human and non-human primates could be maintained and expressed in nonlymphoblastoid cells. Data obtained thus far suggest that at least one characteristic associated with cellular transformation (loss of contact inhibition) is expressed only in nonlymphoblastoid cells in which the EBV genome is maintained. In addition, we have demonstrated that human epithelial/Burkitt hybrid cells (D98/HR-1 and D98/Raji) are more oncogenic in nude (athymic) mice than are cells of the human epithelial parental line, D98, or one of the Burkitt lymphoblastoid parent cell lines (Raji); the HR-1 Burkitt parent cell line was as oncogenic as the hybrid cell lines but the time required to induce tumors was much longer. Thus, human epithelial cells show alteration of growth properties in vitro and in vivo after cellular hybridization with Burkitt tumor cells.", "contents": "Enhanced oncogenic behavior of human and mouse cells after cellular hybridization with Burkitt tumor cells. Studies were made of the expression of the Epstein-Barr virus (EBV) in somatic hybrids of Burkitt tumor cells and human or mouse cells to determine whether EBV genetic information associated with the capacity to transform leukocytes of human and non-human primates could be maintained and expressed in nonlymphoblastoid cells. Data obtained thus far suggest that at least one characteristic associated with cellular transformation (loss of contact inhibition) is expressed only in nonlymphoblastoid cells in which the EBV genome is maintained. In addition, we have demonstrated that human epithelial/Burkitt hybrid cells (D98/HR-1 and D98/Raji) are more oncogenic in nude (athymic) mice than are cells of the human epithelial parental line, D98, or one of the Burkitt lymphoblastoid parent cell lines (Raji); the HR-1 Burkitt parent cell line was as oncogenic as the hybrid cell lines but the time required to induce tumors was much longer. Thus, human epithelial cells show alteration of growth properties in vitro and in vivo after cellular hybridization with Burkitt tumor cells."}
{"id": "PMID:196294", "title": "Cholinergic metabolism and synapse formation by a rat nerve cell line.", "content": "The PC12 clone of a rat pheochromocytoma is able to synthesize acetylcholine. The amount of acetylcholine synthesized, and the specific activity of choline O-acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6), varies as a function of the culture growth curve and is dependent on cell density. The specific activity of choline acetyltransferase is increased by nerve growth factor, growth-conditioned medium from a variety of cell types, and adenosine 3':5'-monophosphate. Finally, the PC12 cell line is able to form cholinergic synapses with a clonal cell line of skeletal muscle origin.", "contents": "Cholinergic metabolism and synapse formation by a rat nerve cell line. The PC12 clone of a rat pheochromocytoma is able to synthesize acetylcholine. The amount of acetylcholine synthesized, and the specific activity of choline O-acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6), varies as a function of the culture growth curve and is dependent on cell density. The specific activity of choline acetyltransferase is increased by nerve growth factor, growth-conditioned medium from a variety of cell types, and adenosine 3':5'-monophosphate. Finally, the PC12 cell line is able to form cholinergic synapses with a clonal cell line of skeletal muscle origin."}
{"id": "PMID:196295", "title": "Effects of electroshock and drugs administered in vivo on protein kinase activity in rat brain.", "content": "The effect of electroshock and treatment with reserpine, amphetamine or lithium chloride on protein kinase activity in synaptic membrane fragments prepared from rat brain was investigated. Naive rats subjected to electroshock procedures showed significant increases in both basal and cyclic AMP-stimulated activity irrespective of whether the treatment was sham, acute or chronic. These increases did not occur in animals which had been tamed by daily handling for 15 days prior to treatment, suggesting that the response was induced by the stress of an unfamiliar situation. Administration of lithium chloride and reserpine caused a small but significant increase in the stimulated activity. Doses of d-amphetamine of 5 mg/kg had no effect on either basal or stimulated activity, but higher doses (up to 15 mg/kg) resulted in a pronounced increase in both activities, which may have been related to drug-induced stress.", "contents": "Effects of electroshock and drugs administered in vivo on protein kinase activity in rat brain. The effect of electroshock and treatment with reserpine, amphetamine or lithium chloride on protein kinase activity in synaptic membrane fragments prepared from rat brain was investigated. Naive rats subjected to electroshock procedures showed significant increases in both basal and cyclic AMP-stimulated activity irrespective of whether the treatment was sham, acute or chronic. These increases did not occur in animals which had been tamed by daily handling for 15 days prior to treatment, suggesting that the response was induced by the stress of an unfamiliar situation. Administration of lithium chloride and reserpine caused a small but significant increase in the stimulated activity. Doses of d-amphetamine of 5 mg/kg had no effect on either basal or stimulated activity, but higher doses (up to 15 mg/kg) resulted in a pronounced increase in both activities, which may have been related to drug-induced stress."}
{"id": "PMID:196299", "title": "Evidence for nuclear sites of stereospecific opiate binding in neuroblastoma cells in continuous culture.", "content": "A class of stereospecific, saturable receptors for narcotic drugs has been found in a clone of mouse neuroblastoma cells in continuous culture. Cells grown in the presence of 10(-8) M etorphine, a synthetic opiate, had an increased doubling time. The neuroblastoma cell nucleus was found to be the sole site for the high affinity binding of etorphine. It was found that these nuclear receptors (1) became saturated at a concentration of 2 X 10(-9) M etorphine, (2) had a dissociation constant of 5 X 10(-11) M etorphine, (3) were capable of binding etorphine stereospecifically at 37 degrees C but not at 4 degree C, and t4) were protein in nature as evidenced by treatment with proteolytic enzymes. More importantly, the receptor activity appeared to be chromatin-associated.", "contents": "Evidence for nuclear sites of stereospecific opiate binding in neuroblastoma cells in continuous culture. A class of stereospecific, saturable receptors for narcotic drugs has been found in a clone of mouse neuroblastoma cells in continuous culture. Cells grown in the presence of 10(-8) M etorphine, a synthetic opiate, had an increased doubling time. The neuroblastoma cell nucleus was found to be the sole site for the high affinity binding of etorphine. It was found that these nuclear receptors (1) became saturated at a concentration of 2 X 10(-9) M etorphine, (2) had a dissociation constant of 5 X 10(-11) M etorphine, (3) were capable of binding etorphine stereospecifically at 37 degrees C but not at 4 degree C, and t4) were protein in nature as evidenced by treatment with proteolytic enzymes. More importantly, the receptor activity appeared to be chromatin-associated."}
{"id": "PMID:196300", "title": "Cellular metabolic control by chemical modification of cell membrane.", "content": "Various reagents used in the chemical modification of amino- and carboxy-groups of proteins, and of carbohydrates of glycoproteins and glycolipids, inhibit respiration in ascites tumor cells concomitant with release of potassium ion from those cells. The respiratory activity of washed ascites tumor cells is increased by exogenous addition of potassium ion. The lowered respiratory control index as well as oxidative phosphorylation of aged mitochondria are restored upon increasing the potassium concentration of the incubation mixture in the presence of respiratory substrates. The data suggest that the potassium ion level of cells is changed by modifying physicochemical properties of membrane components and that cellular energy metabolism is regulated by intracellular potassium ion concentration.", "contents": "Cellular metabolic control by chemical modification of cell membrane. Various reagents used in the chemical modification of amino- and carboxy-groups of proteins, and of carbohydrates of glycoproteins and glycolipids, inhibit respiration in ascites tumor cells concomitant with release of potassium ion from those cells. The respiratory activity of washed ascites tumor cells is increased by exogenous addition of potassium ion. The lowered respiratory control index as well as oxidative phosphorylation of aged mitochondria are restored upon increasing the potassium concentration of the incubation mixture in the presence of respiratory substrates. The data suggest that the potassium ion level of cells is changed by modifying physicochemical properties of membrane components and that cellular energy metabolism is regulated by intracellular potassium ion concentration."}
{"id": "PMID:196305", "title": "Possible involvement of 5-hydroxytryptamine and cyclic-AMP in tolerance to tremorine analgesia in mice.", "content": "The phenomenon of tolerance to the analgesic action of tremorine in mice was studied by the hot-plate and tail-clip methods. Reduction in 5-HT levels in brain by parachlorophenylalamine pretreatment decreased the ED50 of tremorine analgesia in tremorine tolerant mice. 5-Hydroxyptophan, L-Dopa or alpha-methyl-para-tyrosine did not influence the analgesic response to tremorine in tremorine tolerant animals. However, theophylline was found to enhance the tolerance to tremorine analgesia. Brain 5-HT and cAMP are probably involved in tremorine tolerance, whereas neither noradrenaline nor dopamine is involved in the phenomenon.", "contents": "Possible involvement of 5-hydroxytryptamine and cyclic-AMP in tolerance to tremorine analgesia in mice. The phenomenon of tolerance to the analgesic action of tremorine in mice was studied by the hot-plate and tail-clip methods. Reduction in 5-HT levels in brain by parachlorophenylalamine pretreatment decreased the ED50 of tremorine analgesia in tremorine tolerant mice. 5-Hydroxyptophan, L-Dopa or alpha-methyl-para-tyrosine did not influence the analgesic response to tremorine in tremorine tolerant animals. However, theophylline was found to enhance the tolerance to tremorine analgesia. Brain 5-HT and cAMP are probably involved in tremorine tolerance, whereas neither noradrenaline nor dopamine is involved in the phenomenon."}
{"id": "PMID:196306", "title": "Sites of action of morphine involved in the development of physical dependence in rats. III. Autoradiographic studies.", "content": "Morphine withdrawal was precipitated by injection of 3H-naloxone into restricted parts of the ventricular system of rats made tolerant to and dependent on morphine by repeated pellet implantation. The spread of the drug was evaluated by autoradiography and compared with the withdrawal signs precipitated in the same experiment. When the antagonist could spread into the tissue surrounding the 4th ventricle and the caudal parts of the aqueduct (penetration depth about 1.5 mm), a strong withdrawal syndrome was displayed. In contrast, only weak or no withdrawal signs were observed when the spread of naloxone was restricted to the surroundings of the lateral ventricles, the 3rd ventricle, and the rostromedial parts of the aqueduct. The same was true when the spread of the antagonist was limited to the ventral surface of the brain stem. It is concluded that structures located in the anterior part of the fossa Rhomboidea, and possibly also in the caudal part of the periaqueductal grey matter, are sites for the development of physical dependence on morphine giving rise to the withdrawal signs studied in these experiments.", "contents": "Sites of action of morphine involved in the development of physical dependence in rats. III. Autoradiographic studies. Morphine withdrawal was precipitated by injection of 3H-naloxone into restricted parts of the ventricular system of rats made tolerant to and dependent on morphine by repeated pellet implantation. The spread of the drug was evaluated by autoradiography and compared with the withdrawal signs precipitated in the same experiment. When the antagonist could spread into the tissue surrounding the 4th ventricle and the caudal parts of the aqueduct (penetration depth about 1.5 mm), a strong withdrawal syndrome was displayed. In contrast, only weak or no withdrawal signs were observed when the spread of naloxone was restricted to the surroundings of the lateral ventricles, the 3rd ventricle, and the rostromedial parts of the aqueduct. The same was true when the spread of the antagonist was limited to the ventral surface of the brain stem. It is concluded that structures located in the anterior part of the fossa Rhomboidea, and possibly also in the caudal part of the periaqueductal grey matter, are sites for the development of physical dependence on morphine giving rise to the withdrawal signs studied in these experiments."}
{"id": "PMID:196312", "title": "Incidence of bone metastases in women with minimal and occult breast carcinoma.", "content": "A total of 42 women with proved minimal (14) or occult (28) breast carcinoma were evaluated for up to 48 months (mean = 28 months). Bone scans, radiographs, blood chemistries, enzyme levels, and operative findings demonstrated metastases only in those 6 patients (14%) who presented with symptomatic metastases from an unknown primary source. The other 36 women are free of metastases. Preoperative radionuclide bone scans may not be necessary for women with minimal and asymptomatic occult breast cancers.", "contents": "Incidence of bone metastases in women with minimal and occult breast carcinoma. A total of 42 women with proved minimal (14) or occult (28) breast carcinoma were evaluated for up to 48 months (mean = 28 months). Bone scans, radiographs, blood chemistries, enzyme levels, and operative findings demonstrated metastases only in those 6 patients (14%) who presented with symptomatic metastases from an unknown primary source. The other 36 women are free of metastases. Preoperative radionuclide bone scans may not be necessary for women with minimal and asymptomatic occult breast cancers."}
{"id": "PMID:196313", "title": "What causes lower neck uptake in bone scans?", "content": "Lower neck uptake, frequently seen on anterior views of bone scans done with 99mTc-phosphate compounds, was studied in 122 patients to determine its incidence and etiology. Increased uptake was identified in the lower neck anteriorly in 46 patients (38%). In 14 of these, moderately severe to severe arthritis appeared to cause the uptake; metastatic disease was the cause in 8 cases; and in 1 case there was prominent uptake in the thyroid cartilage. Positioning artifact accounted for the uptake in the other 23 cases. Thyroid uptake was never observed.", "contents": "What causes lower neck uptake in bone scans? Lower neck uptake, frequently seen on anterior views of bone scans done with 99mTc-phosphate compounds, was studied in 122 patients to determine its incidence and etiology. Increased uptake was identified in the lower neck anteriorly in 46 patients (38%). In 14 of these, moderately severe to severe arthritis appeared to cause the uptake; metastatic disease was the cause in 8 cases; and in 1 case there was prominent uptake in the thyroid cartilage. Positioning artifact accounted for the uptake in the other 23 cases. Thyroid uptake was never observed."}
{"id": "PMID:196314", "title": "Radiography and scintigraphy in tumoral calcinosis.", "content": "A case of tumoral calcinosis with tumoral deposits about the knee is reported. Radiographs demonstrate juxta-articular calcific deposits about the right second and fifth distal interphalangeal joints and the left first distal tuft, both hips, both shoulders, first distal phalanx of the left foot and right knee. Radionuclide images clearly demonstrate all areas of tumoral calcinosis.", "contents": "Radiography and scintigraphy in tumoral calcinosis. A case of tumoral calcinosis with tumoral deposits about the knee is reported. Radiographs demonstrate juxta-articular calcific deposits about the right second and fifth distal interphalangeal joints and the left first distal tuft, both hips, both shoulders, first distal phalanx of the left foot and right knee. Radionuclide images clearly demonstrate all areas of tumoral calcinosis."}
{"id": "PMID:196315", "title": "A comparative evaluation of a case of cystosarcoma phylloides: ultrasound, xeroradiography and thermography.", "content": "The results of xeroradiography, thermography, and ultrasonic gray scale echography in a case of cystosarcoma phylloides are presented. Echography better described the lesion than the other techniques. Gray scale echography displays the infrastructure of the breast tissues and differentiates between types of soft tissue.", "contents": "A comparative evaluation of a case of cystosarcoma phylloides: ultrasound, xeroradiography and thermography. The results of xeroradiography, thermography, and ultrasonic gray scale echography in a case of cystosarcoma phylloides are presented. Echography better described the lesion than the other techniques. Gray scale echography displays the infrastructure of the breast tissues and differentiates between types of soft tissue."}
{"id": "PMID:196316", "title": "Chromatographic patterns of prostaglandins using different lots of silicic acid.", "content": "The chromatographic patterns of prostaglandin E2 chromatographed on various lots of silicic acid are presented. Two lots of Mallinckrodt silicic acid tested give totally unsatisfactory separation of PGE2. Sigma silicic acid SIL-R gives better separation than any of the Mallinckrodt lots tested. Increasing the size of the \"E\" fraction of solvent can give satisfactory separation on Mallinckrodt silicic acid.", "contents": "Chromatographic patterns of prostaglandins using different lots of silicic acid. The chromatographic patterns of prostaglandin E2 chromatographed on various lots of silicic acid are presented. Two lots of Mallinckrodt silicic acid tested give totally unsatisfactory separation of PGE2. Sigma silicic acid SIL-R gives better separation than any of the Mallinckrodt lots tested. Increasing the size of the \"E\" fraction of solvent can give satisfactory separation on Mallinckrodt silicic acid."}
{"id": "PMID:196317", "title": "Inhibition of prostaglandin synthesis in mouse 3T3 fibroblasts and human platelets by substituted phenols.", "content": "Several substituted phenols with antioxidant properties were potent reversible inhibitors of prostaglandin synthesis in 3T3 cell cultures. The ID50's for prostaglandin (PG) E2 synthesis in these cells were 0.1 muM for 2,6-xylenol, 5 muM for tricresol, 6 muM for p-cresol, 7 muM for o-cresol, 15 muM for 3,5-xylenol, 30 muM for m-cresol and 100 muM for phenol. The corresponding values for aspirin and indomethacin were 4 muM and 0.02 muM, respectively. The substituted phenols also inhibited serotinin release, aggregation and prostaglandin synthesis in human platelets induced by arachidonic acid but not by PGG2.", "contents": "Inhibition of prostaglandin synthesis in mouse 3T3 fibroblasts and human platelets by substituted phenols. Several substituted phenols with antioxidant properties were potent reversible inhibitors of prostaglandin synthesis in 3T3 cell cultures. The ID50's for prostaglandin (PG) E2 synthesis in these cells were 0.1 muM for 2,6-xylenol, 5 muM for tricresol, 6 muM for p-cresol, 7 muM for o-cresol, 15 muM for 3,5-xylenol, 30 muM for m-cresol and 100 muM for phenol. The corresponding values for aspirin and indomethacin were 4 muM and 0.02 muM, respectively. The substituted phenols also inhibited serotinin release, aggregation and prostaglandin synthesis in human platelets induced by arachidonic acid but not by PGG2."}
{"id": "PMID:196320", "title": "[Malignant hepatoma (clinical, biological and morphological comparisons)].", "content": "The authors make an analysis of 8 cases of malignant hepatoma discovered in 20 362 surgical patients between 1965 and 1975. The analysis of these cases allowed to conclude as follows: 1). In the presence of chronic digestive disturbances, or of hepato-splenomegaly, accompanied by progressive deterioration of the general condition of the patient, and of the use of large amounts of analgetic drugs, one should consider more than usually the possibility of hepatic neoplasia. 2). The first element to be considered in the frame of diagnosis of malignant hepatomas should be the morphological one. Of practical value in the diagnostic are the following: hepatic scintigraphy, angiography and bioptic laparotomy. 3). Of the conventional biologic tests (including the immunological tests), evaluation of serum alpha-foetoprotein is the only one with an orientative diagnostic value.", "contents": "[Malignant hepatoma (clinical, biological and morphological comparisons)]. The authors make an analysis of 8 cases of malignant hepatoma discovered in 20 362 surgical patients between 1965 and 1975. The analysis of these cases allowed to conclude as follows: 1). In the presence of chronic digestive disturbances, or of hepato-splenomegaly, accompanied by progressive deterioration of the general condition of the patient, and of the use of large amounts of analgetic drugs, one should consider more than usually the possibility of hepatic neoplasia. 2). The first element to be considered in the frame of diagnosis of malignant hepatomas should be the morphological one. Of practical value in the diagnostic are the following: hepatic scintigraphy, angiography and bioptic laparotomy. 3). Of the conventional biologic tests (including the immunological tests), evaluation of serum alpha-foetoprotein is the only one with an orientative diagnostic value."}
{"id": "PMID:196327", "title": "Cyclic Amp and the release of antral gastrin.", "content": "The isolated, vagally innervated antral pouches in anesthetized dogs were irrigated with 095% acetylcholine chloride (Ach) or a 0.4 M mixture of non-essential amino acids (AA), or distended at 30 cm H2O pressure. In addition,2-deoxy-D-glucose (2-DG) was administered intravenously. Significant increases in antral venous gastrin, caused by gastrin releasers, were associated with a significant rise in cAMP content in the antral mucosa. Acidification of the antrum with simultaneous administration of 2-DG, and acidified AA abolished gastrin release, and significantly reduced mucosal cAMP. Acidified Ach and distension of the antrum with 0.1 N HC1 supressed gastrin levels without significantly changing the mucosal cAMP content. Since the augmented gastrin release was accompanied by an increased mucosal cAMP, the results suggest that cAMP participates in the action of gastrin secretagogues.", "contents": "Cyclic Amp and the release of antral gastrin. The isolated, vagally innervated antral pouches in anesthetized dogs were irrigated with 095% acetylcholine chloride (Ach) or a 0.4 M mixture of non-essential amino acids (AA), or distended at 30 cm H2O pressure. In addition,2-deoxy-D-glucose (2-DG) was administered intravenously. Significant increases in antral venous gastrin, caused by gastrin releasers, were associated with a significant rise in cAMP content in the antral mucosa. Acidification of the antrum with simultaneous administration of 2-DG, and acidified AA abolished gastrin release, and significantly reduced mucosal cAMP. Acidified Ach and distension of the antrum with 0.1 N HC1 supressed gastrin levels without significantly changing the mucosal cAMP content. Since the augmented gastrin release was accompanied by an increased mucosal cAMP, the results suggest that cAMP participates in the action of gastrin secretagogues."}
{"id": "PMID:196328", "title": "Mechanisms of the H-2 effect on viral leukemogenesis.", "content": "Evidence has been gathered which supports the notion that two distinct but interacting mechanisms, controlled by loci mapping within the H-2 complex, influence Friend murine leukemia virus (FV) disease. One mechanism, controlled by a gene mapping in or close to H-2D, influences the capacity of the H-2D gene product to form molecular complexes with FV molecules in the plasma membrane of infected cells. Formation of a complex appears to provide a target antigen for syngeneic cytotoxic T-lymphocytes, to cause co-capping of FV and H-2D antigens, to permit the selective inclusion of H-2Db molecules into progeny Friend virions, to influence the long-term maintenance of virus production in vitro and, in conjunction with the second mechanism, to stimulate the generation of cytotoxic T-lymphocytes. This second mechanism is controlled by a gene in the H-2K or H-2I region, and, in the presence of an H-2/FV molecular complex immunogen, influences the generation of H-2 restricted cytotxic T-lymphocytes and the rate of rejection of syngeneic FV-induced tumor cells.", "contents": "Mechanisms of the H-2 effect on viral leukemogenesis. Evidence has been gathered which supports the notion that two distinct but interacting mechanisms, controlled by loci mapping within the H-2 complex, influence Friend murine leukemia virus (FV) disease. One mechanism, controlled by a gene mapping in or close to H-2D, influences the capacity of the H-2D gene product to form molecular complexes with FV molecules in the plasma membrane of infected cells. Formation of a complex appears to provide a target antigen for syngeneic cytotoxic T-lymphocytes, to cause co-capping of FV and H-2D antigens, to permit the selective inclusion of H-2Db molecules into progeny Friend virions, to influence the long-term maintenance of virus production in vitro and, in conjunction with the second mechanism, to stimulate the generation of cytotoxic T-lymphocytes. This second mechanism is controlled by a gene in the H-2K or H-2I region, and, in the presence of an H-2/FV molecular complex immunogen, influences the generation of H-2 restricted cytotxic T-lymphocytes and the rate of rejection of syngeneic FV-induced tumor cells."}
{"id": "PMID:196329", "title": "[Familial cancer syndrome studies in 4 generations of a family].", "content": "An account is given of a family from the Canton of Valais suffering from hereditary adenocarcinomatosis. The pedigree extends over four generations; the first three comprised 47 individuals (28 males, 19 females), of whom 21 (16 males and 5 females), i.e. 44.6%, have malignant tumors. Of the 32 people in the fourth generation, only one individual is affected to date (a girl age 21, IV/4). There were 27 tumors in all: 16 adenocarcinomas of the colon, two gastric adenocarcinomas, one duodenal adenocarcinoma, one rectal adenocarcinoma, one papillary carcinoma of the ovary, one osseous sarcoma, one cutaneous fibrosarcoma, a multiform glioblastoma of the basal nuclei of the brain, a basocellular epithelioma, a cerebral metastasis from an adenocarcinoma, the origine of which has not been established, and a tumor invading the biliary tract. Three members of the family had multiple tumors. In three of the patient the colonic adenocarcinoma was accompanied by one or two polyps. The average age at onset for all tumors was 45 years. It was definitely lower in the third than the second generation (anticipation). The transmission was autosomal dominant, with predilection for the male sex (57.1% male and 26.3% female patients). The penetrance was about 80%. Finally, the diagnostic criteria for hereditary adenocarcinoma are discussed and the different familial forms of cancer are reviewed.", "contents": "[Familial cancer syndrome studies in 4 generations of a family]. An account is given of a family from the Canton of Valais suffering from hereditary adenocarcinomatosis. The pedigree extends over four generations; the first three comprised 47 individuals (28 males, 19 females), of whom 21 (16 males and 5 females), i.e. 44.6%, have malignant tumors. Of the 32 people in the fourth generation, only one individual is affected to date (a girl age 21, IV/4). There were 27 tumors in all: 16 adenocarcinomas of the colon, two gastric adenocarcinomas, one duodenal adenocarcinoma, one rectal adenocarcinoma, one papillary carcinoma of the ovary, one osseous sarcoma, one cutaneous fibrosarcoma, a multiform glioblastoma of the basal nuclei of the brain, a basocellular epithelioma, a cerebral metastasis from an adenocarcinoma, the origine of which has not been established, and a tumor invading the biliary tract. Three members of the family had multiple tumors. In three of the patient the colonic adenocarcinoma was accompanied by one or two polyps. The average age at onset for all tumors was 45 years. It was definitely lower in the third than the second generation (anticipation). The transmission was autosomal dominant, with predilection for the male sex (57.1% male and 26.3% female patients). The penetrance was about 80%. Finally, the diagnostic criteria for hereditary adenocarcinoma are discussed and the different familial forms of cancer are reviewed."}
{"id": "PMID:196331", "title": "Correlation between lipid synthesis in tumor cells and their sensitivity to humoral immune attack.", "content": "Prolonged incubation of two antigenically distinct, chemically induced guinea pig hepatomas with relatively high concentrations of chemotherapeutic drugs or metabolic inhibitors increases their susceptibility to killing by antibody and complement. This effect is reversible when the cells are cultured in the absence of the drugs. The drug-induced sensitivity and the ability of the cells to recover their resistance to killing are directly correlated to their ability to synthesize complex lipids.", "contents": "Correlation between lipid synthesis in tumor cells and their sensitivity to humoral immune attack. Prolonged incubation of two antigenically distinct, chemically induced guinea pig hepatomas with relatively high concentrations of chemotherapeutic drugs or metabolic inhibitors increases their susceptibility to killing by antibody and complement. This effect is reversible when the cells are cultured in the absence of the drugs. The drug-induced sensitivity and the ability of the cells to recover their resistance to killing are directly correlated to their ability to synthesize complex lipids."}
{"id": "PMID:196332", "title": "Dopamine and adenosine 3',5'-monophosphate responses of single mammalian sympathetic neurons.", "content": "Acetylcholine (ACh), dopamine, and dibutyryl-adenosine 3',5'-monophosphate (dbcAMP) were applied iontophoretically to the rabbit superior cervical ganglion cells from triple-barreled micropipettes, and the response was recorded by intracellular techniques. All ganglion cells tested responded to the depolarizing action of ACh, whereas less than half of the cells that responded to ACh were hyperpolarized by dopamine. This effect was blocked by low concentrations of haloperidol. None of the cells examined responded to dbcAMP applied by iontophoresis. Hence, the present result is not consistent with the concept that a cyclic AMP mechanism underlies the hyperpolarizing effect of dopamine.", "contents": "Dopamine and adenosine 3',5'-monophosphate responses of single mammalian sympathetic neurons. Acetylcholine (ACh), dopamine, and dibutyryl-adenosine 3',5'-monophosphate (dbcAMP) were applied iontophoretically to the rabbit superior cervical ganglion cells from triple-barreled micropipettes, and the response was recorded by intracellular techniques. All ganglion cells tested responded to the depolarizing action of ACh, whereas less than half of the cells that responded to ACh were hyperpolarized by dopamine. This effect was blocked by low concentrations of haloperidol. None of the cells examined responded to dbcAMP applied by iontophoresis. Hence, the present result is not consistent with the concept that a cyclic AMP mechanism underlies the hyperpolarizing effect of dopamine."}
{"id": "PMID:196333", "title": "Conformations of prostaglandin F 2alpha and recognition of prostaglandins by their receptors.", "content": "The conformation of prostaglandin F 2alpha (PGF 2alpha) has been determined by x-ray diffraction techniques. Two independent conformers of PGF 2alpha, studied as the tris(hydroxymethyl)methylamine salt, are observed to adopt the familiar \"hairpin\" conformation with the alpha and omega chains aligned roughly parallel. The conformers differ in ring conformation and at the C(17)-C(18) bond, one adopting a C(9) envelope ring conformation and a trans geometry at the C(17)-C(18) bond, while the other adopts a C(8) envelope ring conformation and a novel gauche geometry about C(17)-C(18). Comparison of the conformation of PGF 2alpha with that of prostaglandin E2 suggests a recognition mechanism which would permit PGF 2alpha and prostaglandin E receptors to distinguish between the two potent prostaglandins. The recognition model explains much of the binding data for the PGF 2alpha receptor in the corpus luteum and predicts the existence of an interesting PGF 2alpha analog.", "contents": "Conformations of prostaglandin F 2alpha and recognition of prostaglandins by their receptors. The conformation of prostaglandin F 2alpha (PGF 2alpha) has been determined by x-ray diffraction techniques. Two independent conformers of PGF 2alpha, studied as the tris(hydroxymethyl)methylamine salt, are observed to adopt the familiar \"hairpin\" conformation with the alpha and omega chains aligned roughly parallel. The conformers differ in ring conformation and at the C(17)-C(18) bond, one adopting a C(9) envelope ring conformation and a trans geometry at the C(17)-C(18) bond, while the other adopts a C(8) envelope ring conformation and a novel gauche geometry about C(17)-C(18). Comparison of the conformation of PGF 2alpha with that of prostaglandin E2 suggests a recognition mechanism which would permit PGF 2alpha and prostaglandin E receptors to distinguish between the two potent prostaglandins. The recognition model explains much of the binding data for the PGF 2alpha receptor in the corpus luteum and predicts the existence of an interesting PGF 2alpha analog."}
{"id": "PMID:196334", "title": "Thyroid hormone action: the mitochondrial pathway.", "content": "The subcellular compartments have been investigated to compare proteins capable of binding triiodothyronine and thyroxine; specific binders have been found in cytosol, nuclei, and mitochondria from rat liver and kidney. The binding protein from the inner mitochondrial membrane had the highest association constant (greater than 10(11) liters per mole), suggesting possible direct hormone action on the mitochondria. Binding of hormone analogs was found to be related to known physiological potency, and stereospecific discrimination between L- and D-thyroxine was observed. The saturable receptor was found in the mitochondrial membranes of rat liver, kidney, myocardium, and skeletal muscle but not in mitochondria from the unresponsive tissues: brain, spleen, and testis. Oxidative phosphorylation by mitochondrial vesicles from hypothyroid rats increased after the addition of physiological concentrations of triiodothyronine, which corroborated direct hormone action on mitochondria.", "contents": "Thyroid hormone action: the mitochondrial pathway. The subcellular compartments have been investigated to compare proteins capable of binding triiodothyronine and thyroxine; specific binders have been found in cytosol, nuclei, and mitochondria from rat liver and kidney. The binding protein from the inner mitochondrial membrane had the highest association constant (greater than 10(11) liters per mole), suggesting possible direct hormone action on the mitochondria. Binding of hormone analogs was found to be related to known physiological potency, and stereospecific discrimination between L- and D-thyroxine was observed. The saturable receptor was found in the mitochondrial membranes of rat liver, kidney, myocardium, and skeletal muscle but not in mitochondria from the unresponsive tissues: brain, spleen, and testis. Oxidative phosphorylation by mitochondrial vesicles from hypothyroid rats increased after the addition of physiological concentrations of triiodothyronine, which corroborated direct hormone action on mitochondria."}
{"id": "PMID:196335", "title": "Axial bending in the early chick embryo by a cyclic adenosine monophosphate source.", "content": "A microelectrode continuously releasing cyclic adenosine monophosphate can divert the axis of the early chick embryo and attract cells on its ventral surface. Cell movement in the intact embryo may be controlled by a cyclic adenosine monophosphate signal.", "contents": "Axial bending in the early chick embryo by a cyclic adenosine monophosphate source. A microelectrode continuously releasing cyclic adenosine monophosphate can divert the axis of the early chick embryo and attract cells on its ventral surface. Cell movement in the intact embryo may be controlled by a cyclic adenosine monophosphate signal."}
{"id": "PMID:196336", "title": "Rous sarcomas in chickens: enhanced growth coexisting with concomitant immunity.", "content": "Chickens bearing Rous sarcoma virus-induced tumors in one wing did not develop new tumors when subsequently inoculated with Rous sarcoma virus in the other wing. However, the second inoculation of Rous sarcoma virus caused accelerated growth of the established tumors. This phenomenon was found to be bursa-dependent. Paradoxically, established tumors in bursectomized chickens grew at a diminished rate if the chickens were reinoculated with Rous sarcoma virus.", "contents": "Rous sarcomas in chickens: enhanced growth coexisting with concomitant immunity. Chickens bearing Rous sarcoma virus-induced tumors in one wing did not develop new tumors when subsequently inoculated with Rous sarcoma virus in the other wing. However, the second inoculation of Rous sarcoma virus caused accelerated growth of the established tumors. This phenomenon was found to be bursa-dependent. Paradoxically, established tumors in bursectomized chickens grew at a diminished rate if the chickens were reinoculated with Rous sarcoma virus."}
{"id": "PMID:196337", "title": "[Acute oligoanuric renal insufficiency in malignant nephroangiosclerosis].", "content": "The concept of acute renal failure with anuria due to malignant nephro-angiosclerosis, is uncommon. We report two cases and compare them with others in the world literature. Knowledge of this disease entity is of triple interest: In diagnosis and classification in the field of acute vascular nephropathy with anuria. We cannot emphasise too much the interest of early renal biopsy after correction of abnormal blood pressure. In physiopathology, these malignant nephro-angioscleroses give rise to hypertension of pressor type with high renin levels. Finally therapeutic, for there exist drugs adapted to this type of hypertension. The association of acute renal failure and malignant nephro-angiosclerosis should be treated as an emergency, to avoid the passage to terminal and irreversible renal failure.", "contents": "[Acute oligoanuric renal insufficiency in malignant nephroangiosclerosis]. The concept of acute renal failure with anuria due to malignant nephro-angiosclerosis, is uncommon. We report two cases and compare them with others in the world literature. Knowledge of this disease entity is of triple interest: In diagnosis and classification in the field of acute vascular nephropathy with anuria. We cannot emphasise too much the interest of early renal biopsy after correction of abnormal blood pressure. In physiopathology, these malignant nephro-angioscleroses give rise to hypertension of pressor type with high renin levels. Finally therapeutic, for there exist drugs adapted to this type of hypertension. The association of acute renal failure and malignant nephro-angiosclerosis should be treated as an emergency, to avoid the passage to terminal and irreversible renal failure."}
{"id": "PMID:196338", "title": "[Radiologic study of arterial calcifications of the lower extremities in diabetic patients].", "content": "The authors analyse the frequency of arterial calcifications in the lower limbs in diabetics. These calcifications were found in the thighs and legs and also in the feet. They were more frequent in diabetics than in normal subjects and occurred earlier in life. Their presence showed the existence of a severe microangiopathic process.", "contents": "[Radiologic study of arterial calcifications of the lower extremities in diabetic patients]. The authors analyse the frequency of arterial calcifications in the lower limbs in diabetics. These calcifications were found in the thighs and legs and also in the feet. They were more frequent in diabetics than in normal subjects and occurred earlier in life. Their presence showed the existence of a severe microangiopathic process."}
{"id": "PMID:196339", "title": "[Initial trial of a new test for the evaluation of hepatocellular function: the TMB test].", "content": "The oral administration of 400 mg of trimethoxy 1-3-5-benzene or T.M.B. is normally followed by a high urinary excretion of dimethoxy, 1, 3, hydroxy 5 benzene and other metabolites mainly in the form of conjugates. Urinary excretion during the first 3 hours is strongly reduced in liver disease. By a simple blind test we showed that the test is positive in subclinical and laboratory-negative liver failure.", "contents": "[Initial trial of a new test for the evaluation of hepatocellular function: the TMB test]. The oral administration of 400 mg of trimethoxy 1-3-5-benzene or T.M.B. is normally followed by a high urinary excretion of dimethoxy, 1, 3, hydroxy 5 benzene and other metabolites mainly in the form of conjugates. Urinary excretion during the first 3 hours is strongly reduced in liver disease. By a simple blind test we showed that the test is positive in subclinical and laboratory-negative liver failure."}
{"id": "PMID:196340", "title": "[Intra-articular iron sequestration and rheumatic anemia. Histologic and isotopic study].", "content": "The authors explored 48 patients with various forms of inflammatory rheumatism and 8 controls. The exploration consisted of seeking in the synovial membrane ferric pigments by Perls stain, or studying the movements of Fe 59 bound to siderophyllin in the joints. Intra-articular iron deposits were thus demonstrated only in the inflammatory cases. Its mechanism is discussed. It seems sufficient to be the cause of rheumatic anemia which is thus different from other forms of inflammatory anemia owing to the importance of the iron uptake.", "contents": "[Intra-articular iron sequestration and rheumatic anemia. Histologic and isotopic study]. The authors explored 48 patients with various forms of inflammatory rheumatism and 8 controls. The exploration consisted of seeking in the synovial membrane ferric pigments by Perls stain, or studying the movements of Fe 59 bound to siderophyllin in the joints. Intra-articular iron deposits were thus demonstrated only in the inflammatory cases. Its mechanism is discussed. It seems sufficient to be the cause of rheumatic anemia which is thus different from other forms of inflammatory anemia owing to the importance of the iron uptake."}
{"id": "PMID:196341", "title": "[Immunologic status of women of western Brittany with regard to the Torch complex (toxoplasmosis, rubella, cytomegalovirus, herpes); necessity of a polyvalent serologic surveillance in pregnancy].", "content": "We have carried out a sero-epidemiological investigation with regard to the \"Torch complex\" in 702 women aged from 11 to 49 years and living in an urban district of the Finistere or Morbihan. The proportion of protected women was relatively low compared with other regions of France: 50.14% for toxoplasmosis 74.64% for rubella, 23.70% for cytomegalovirus and 39.61% for herpes. Furthermore, no woman had any antibodies for the virus of lymphocytic choriomeningitis, another potentially teratogenic virus. It thus seems advisable to supervise the serology of pregnant women in our region for the whole of the Torch complex. The practical modalities and the choice of serological reactions are discussed.", "contents": "[Immunologic status of women of western Brittany with regard to the Torch complex (toxoplasmosis, rubella, cytomegalovirus, herpes); necessity of a polyvalent serologic surveillance in pregnancy]. We have carried out a sero-epidemiological investigation with regard to the \"Torch complex\" in 702 women aged from 11 to 49 years and living in an urban district of the Finistere or Morbihan. The proportion of protected women was relatively low compared with other regions of France: 50.14% for toxoplasmosis 74.64% for rubella, 23.70% for cytomegalovirus and 39.61% for herpes. Furthermore, no woman had any antibodies for the virus of lymphocytic choriomeningitis, another potentially teratogenic virus. It thus seems advisable to supervise the serology of pregnant women in our region for the whole of the Torch complex. The practical modalities and the choice of serological reactions are discussed."}
{"id": "PMID:196351", "title": "Acute haemorrhagic conjunctivitis in Hong Kong 1971-1975.", "content": "Acute haemorrhagic conjunctivitis occurred in epidemic in Hong Kong in 1971 and 1975 respectively. Two picornaviruses, the Enterovirus type 70 and an antigenic variant of Coxsackie virus type A24, were isolated during the 1971 outbreak, while only the latter virus was detected in the 1975 outbreak. In 1972 and 1974, sporadic cases of conjunctivitis associated with Enterovirus type 70 were observed. Serological survey in late 1975 showed a high proportion of the population might still be susceptible to both viruses. Recrudescence of the disease is conceivable when environmental condition is favourable for the spread of these viruses.", "contents": "Acute haemorrhagic conjunctivitis in Hong Kong 1971-1975. Acute haemorrhagic conjunctivitis occurred in epidemic in Hong Kong in 1971 and 1975 respectively. Two picornaviruses, the Enterovirus type 70 and an antigenic variant of Coxsackie virus type A24, were isolated during the 1971 outbreak, while only the latter virus was detected in the 1975 outbreak. In 1972 and 1974, sporadic cases of conjunctivitis associated with Enterovirus type 70 were observed. Serological survey in late 1975 showed a high proportion of the population might still be susceptible to both viruses. Recrudescence of the disease is conceivable when environmental condition is favourable for the spread of these viruses."}
{"id": "PMID:196354", "title": "Alpha-chain disease. A case report with autopsy findings.", "content": "A 19-year-old Coloured man with alpha-chain disease died after perforation of a lymphoma in the duodenojejunal region. At autopsy he was found to have a dense plasma cell infiltration of the lamina propria of the entire small bowel, causing thickening of that organ, and a malignant lymphoma in the duodenojejunal region which had spread to regional mesenteric nodes and to the liver only.", "contents": "Alpha-chain disease. A case report with autopsy findings. A 19-year-old Coloured man with alpha-chain disease died after perforation of a lymphoma in the duodenojejunal region. At autopsy he was found to have a dense plasma cell infiltration of the lamina propria of the entire small bowel, causing thickening of that organ, and a malignant lymphoma in the duodenojejunal region which had spread to regional mesenteric nodes and to the liver only."}
{"id": "PMID:196355", "title": "The effect of practolol and butoxamine on aortic arch malformation in beta adrenoreceptor stimulated chick embryos.", "content": "An equimolar dose of the beta-1 adrenoreceptor antagonist practolol administered to embryonic chicks prevents the induction of aortic arch malformations by isoproterenol. Whereas 3.75 X 10(-9) mole isoproterenol in 5  microliter saline solution induced aortic arch anomalies in 39% of embryos injected at Hamburger-Hamilton developmental stage 26, pretreatment with practolol one to two minutes before catecholamine administration reduced the anomaly rate to to 4%. Practolol when injected alone did not influence survival rate nor did it cause cardiovascular malformations. Probably the most significant result of this study involves the prevention by practolol of aortic hypoplasia and interrupted aortic arch complexes, anomalies frequently induced by isoproterenol when administered at this stage of embryonic chick development. Butoxamine, a beta-2 adrenoreceptor antagonist, did not block the overall effect of isoproterenol nearly as effectively as did practolol. Results from the present study suggest that aortic arch anomalies may be induced in embryonic chicks via beta-1 adrenoreceptor stimulation. Beta-2 receptor stimulation does not appear to be as significantly involved.", "contents": "The effect of practolol and butoxamine on aortic arch malformation in beta adrenoreceptor stimulated chick embryos. An equimolar dose of the beta-1 adrenoreceptor antagonist practolol administered to embryonic chicks prevents the induction of aortic arch malformations by isoproterenol. Whereas 3.75 X 10(-9) mole isoproterenol in 5  microliter saline solution induced aortic arch anomalies in 39% of embryos injected at Hamburger-Hamilton developmental stage 26, pretreatment with practolol one to two minutes before catecholamine administration reduced the anomaly rate to to 4%. Practolol when injected alone did not influence survival rate nor did it cause cardiovascular malformations. Probably the most significant result of this study involves the prevention by practolol of aortic hypoplasia and interrupted aortic arch complexes, anomalies frequently induced by isoproterenol when administered at this stage of embryonic chick development. Butoxamine, a beta-2 adrenoreceptor antagonist, did not block the overall effect of isoproterenol nearly as effectively as did practolol. Results from the present study suggest that aortic arch anomalies may be induced in embryonic chicks via beta-1 adrenoreceptor stimulation. Beta-2 receptor stimulation does not appear to be as significantly involved."}
{"id": "PMID:196356", "title": "ADPase activity of normal and atherosclerotic human aorta intima.", "content": "ADP plays a key role in platelet aggregation and the enzymatic removal of this nucleotide may be important in the pathogenesis of intravascular thrombosis and atherosclerosis. Aortic intima extracts have ADPase activity and is able to remove small quantities of ADP efficiently. ADPase activity was assayed by measuring the catabolism of 2 micrometer 14C-ADP (final concentration) by the tissue extracts. Extracts prepared from normal, moderately and severely atherosclerotic human aortic initimas showed a significant progressive decrease in ADPase activity with increasing atherosclerosis. ADPase activity of the arch, thoracic and abdominal regions of normal aortas did not vary significantly, and thus did not correlate with the anatomical distribution of atherosclerosis. Vascular ADPase activity seems relevant in thrombogenesis since it may be a link between blood platelets and blood vessel wall interaction.", "contents": "ADPase activity of normal and atherosclerotic human aorta intima. ADP plays a key role in platelet aggregation and the enzymatic removal of this nucleotide may be important in the pathogenesis of intravascular thrombosis and atherosclerosis. Aortic intima extracts have ADPase activity and is able to remove small quantities of ADP efficiently. ADPase activity was assayed by measuring the catabolism of 2 micrometer 14C-ADP (final concentration) by the tissue extracts. Extracts prepared from normal, moderately and severely atherosclerotic human aortic initimas showed a significant progressive decrease in ADPase activity with increasing atherosclerosis. ADPase activity of the arch, thoracic and abdominal regions of normal aortas did not vary significantly, and thus did not correlate with the anatomical distribution of atherosclerosis. Vascular ADPase activity seems relevant in thrombogenesis since it may be a link between blood platelets and blood vessel wall interaction."}
{"id": "PMID:196358", "title": "Transmissible gastro-enteritis of swine in the netherlands the application of the direct fluorescent antibody techique for diagnosis.", "content": "The epizootiology of transmissible gastro-enteritis (TGE) of swine in 1975 and 1976 in the Netherlands was studied. Diagnosis was made by the direct fluorescent antibody technique (FAT). Specimens from the small intestine of suspected animals were examined for this purpose. The results obtained by the direct FAT were proved to be reliable, if the specimens were derived from acutely sick animals and examination could be carried out as soon as possible. The results confirmed that TGE occured in any season of the year. The peaks of epizootic outbreaks were in the spring and winter of those years.", "contents": "Transmissible gastro-enteritis of swine in the netherlands the application of the direct fluorescent antibody techique for diagnosis. The epizootiology of transmissible gastro-enteritis (TGE) of swine in 1975 and 1976 in the Netherlands was studied. Diagnosis was made by the direct fluorescent antibody technique (FAT). Specimens from the small intestine of suspected animals were examined for this purpose. The results obtained by the direct FAT were proved to be reliable, if the specimens were derived from acutely sick animals and examination could be carried out as soon as possible. The results confirmed that TGE occured in any season of the year. The peaks of epizootic outbreaks were in the spring and winter of those years."}
{"id": "PMID:196360", "title": "Ultrastructural study of immunoblastic lymphadenopathy.", "content": "An autopsy case of angio-immunoblastic lymphadenopathy with dysproteinemia (Frizzera et al. 1917) or immunoblastic lymphadenopathy (Lukes and Tindle 1975) is reported. Clinical pictures and morphologic characteristics of affected organs were typical of this disease. In spite of combination chemotherapy, the patient took a rapid fatal course. Post-mortem examinations disclosed involvement of the lymph nodes, liver, lungs, kidneys and skin. Cellular infiltrates in the kidney were more monomorphous, suggesting the potential for the development of immunoblastic sarcoma. Electron microscopies of the affected lymph nodes revealed the proliferation of immunoblasts characterized by moderate amount of clear cytoplasm with abundant polyribosomes and by large nuclei with prominent nucleoli. Undulated tubules associated with the endoplasmic reticulum and giant mitochondria with the centrally placed cristae were observed in occasional immunoblasts. Cytoplasmic fragments of immunoblasts and filamentous material among the cells were considered to correspond to the amorphous intercellular material seen in histologic sections.", "contents": "Ultrastructural study of immunoblastic lymphadenopathy. An autopsy case of angio-immunoblastic lymphadenopathy with dysproteinemia (Frizzera et al. 1917) or immunoblastic lymphadenopathy (Lukes and Tindle 1975) is reported. Clinical pictures and morphologic characteristics of affected organs were typical of this disease. In spite of combination chemotherapy, the patient took a rapid fatal course. Post-mortem examinations disclosed involvement of the lymph nodes, liver, lungs, kidneys and skin. Cellular infiltrates in the kidney were more monomorphous, suggesting the potential for the development of immunoblastic sarcoma. Electron microscopies of the affected lymph nodes revealed the proliferation of immunoblasts characterized by moderate amount of clear cytoplasm with abundant polyribosomes and by large nuclei with prominent nucleoli. Undulated tubules associated with the endoplasmic reticulum and giant mitochondria with the centrally placed cristae were observed in occasional immunoblasts. Cytoplasmic fragments of immunoblasts and filamentous material among the cells were considered to correspond to the amorphous intercellular material seen in histologic sections."}
{"id": "PMID:196366", "title": "Neurocristopathies in African subjects.", "content": "The distribution of neural crest cells is briefly reviewed. The behaviour of neural crest derivatives in Africans is different from that seen in Caucasians, both in terms of physiology and pathology. The most obvious variation is in the depth of pigmentation of the skin, but most diseases of neural crest derived tissues show differences between Black and White subjects. The reason for these differences are not readily apparent but appear to be of genetic rather than environmental origin.", "contents": "Neurocristopathies in African subjects. The distribution of neural crest cells is briefly reviewed. The behaviour of neural crest derivatives in Africans is different from that seen in Caucasians, both in terms of physiology and pathology. The most obvious variation is in the depth of pigmentation of the skin, but most diseases of neural crest derived tissues show differences between Black and White subjects. The reason for these differences are not readily apparent but appear to be of genetic rather than environmental origin."}
{"id": "PMID:196367", "title": "[Studies on the Simulium damnosum complex in West Africa - V. Morphological identification of the females in Ivory Coast (author's transl)].", "content": "The morphological identification of adult females of the Simulium damnosum complex is essential for studies on the ecology and vector potential of the species concerned. Detailed morphological studies of adult females obtained at breeding sites, where larvae had been identified cytotaxonomically, allowed the establishment of an identification key. This key, based on morphological characters of the antennae and maxillae, is dealing with the six species of the complex known to occur in the Ivory Coast. It has been used, with success, during ecological and epidemiological studies in the field.", "contents": "[Studies on the Simulium damnosum complex in West Africa - V. Morphological identification of the females in Ivory Coast (author's transl)]. The morphological identification of adult females of the Simulium damnosum complex is essential for studies on the ecology and vector potential of the species concerned. Detailed morphological studies of adult females obtained at breeding sites, where larvae had been identified cytotaxonomically, allowed the establishment of an identification key. This key, based on morphological characters of the antennae and maxillae, is dealing with the six species of the complex known to occur in the Ivory Coast. It has been used, with success, during ecological and epidemiological studies in the field."}
{"id": "PMID:196369", "title": "[Characteristics of the upper cell surface in cultures of normal and SV-40 virus-transformed epithelium of mouse kidney. Study with the aid of scanning electron microscopy].", "content": "Central cells of the normal epithelial sheet are sparsely covered by microvilli. Numerous microvilli were seen in the regions of intercellular contacts. Marginal cells of sheets had a finely developed lamellar cytoplasm (lameloplasm) with smooth upper surface at their free margins. A transformed cell line (MPTR) resembled normal parent cells by its ability to form monolayered sheets in cultures. More microvilli of increased length appeared on the upper surface of central MPTR cells. The normal structure of lamelloplasm was changed at the free edge of the MPTR sheets. It is suggested that abnormal cell attachment to the substratum may be responsible for the altered cell surface morphology (increased length of microvilli, defective, structure of lamelloplasm) in the MPTR cultures.", "contents": "[Characteristics of the upper cell surface in cultures of normal and SV-40 virus-transformed epithelium of mouse kidney. Study with the aid of scanning electron microscopy]. Central cells of the normal epithelial sheet are sparsely covered by microvilli. Numerous microvilli were seen in the regions of intercellular contacts. Marginal cells of sheets had a finely developed lamellar cytoplasm (lameloplasm) with smooth upper surface at their free margins. A transformed cell line (MPTR) resembled normal parent cells by its ability to form monolayered sheets in cultures. More microvilli of increased length appeared on the upper surface of central MPTR cells. The normal structure of lamelloplasm was changed at the free edge of the MPTR sheets. It is suggested that abnormal cell attachment to the substratum may be responsible for the altered cell surface morphology (increased length of microvilli, defective, structure of lamelloplasm) in the MPTR cultures."}
{"id": "PMID:196370", "title": "[Study of structural changes of contractile muscle proteins with the aid of polarization ultraviolet fluorescence microscopy. 1. Conformational changes of F-actin in the muscle fiber caused by ATP and its analogs].", "content": "Increase of anisotropy of F-actin fluorescence of balanus and rabbit muscle fibers under the influence of ATP, AMP and pyrophosphate in EGTA presence was detected by means of the polarized ultraviolet (UV) fluorescent microscopy methods. The fluorescence anisotropy changes are assumed to be associated with the conformational changes in the actin. ATP cause more noticeable changes of actin structure, than pyrophosphate and AMP. The conformational changes in the actin of balanus and rabbit muscle fibres were similar. ATP and its analogs induced also decrease of UV fluorescence anisotropy of A-band which appears to be associated with conformational changes in myosin. It was siggested that the changes in fluorescence of anisotropy of A-bands are due to structural changes in both HMM and LMM parts of myosin molecule.", "contents": "[Study of structural changes of contractile muscle proteins with the aid of polarization ultraviolet fluorescence microscopy. 1. Conformational changes of F-actin in the muscle fiber caused by ATP and its analogs]. Increase of anisotropy of F-actin fluorescence of balanus and rabbit muscle fibers under the influence of ATP, AMP and pyrophosphate in EGTA presence was detected by means of the polarized ultraviolet (UV) fluorescent microscopy methods. The fluorescence anisotropy changes are assumed to be associated with the conformational changes in the actin. ATP cause more noticeable changes of actin structure, than pyrophosphate and AMP. The conformational changes in the actin of balanus and rabbit muscle fibres were similar. ATP and its analogs induced also decrease of UV fluorescence anisotropy of A-band which appears to be associated with conformational changes in myosin. It was siggested that the changes in fluorescence of anisotropy of A-bands are due to structural changes in both HMM and LMM parts of myosin molecule."}
{"id": "PMID:196372", "title": "[Analysis of substances issuing from Zajdela ascitic hepatoma cells after exposure to UV radiation of different wave-lengths. I. Relationship to dose].", "content": "The release of substances from the Zaidela ascitic hepatoma cells after irradiation with physiological doses of short-wave (254 nm) and long-wave (300-380 nm) UV light (far and near UV light) has been studied spectrophotometrically. Within the range of 200-520 nm, the absorption spectra of releasing substances show maxima at 215 and 260 nm and are identical to spectra of non-irradiated cells. The amount of substances increases with dose making up, at the maximal alteration, 180-220%, of the amount releasing from non-irradiated cells. Irradiation with far UV light exceeds by one order that with near UV light. The effect of minimum doses is opposite to the action of high doses: the release of substances from irradiated cells is much less.", "contents": "[Analysis of substances issuing from Zajdela ascitic hepatoma cells after exposure to UV radiation of different wave-lengths. I. Relationship to dose]. The release of substances from the Zaidela ascitic hepatoma cells after irradiation with physiological doses of short-wave (254 nm) and long-wave (300-380 nm) UV light (far and near UV light) has been studied spectrophotometrically. Within the range of 200-520 nm, the absorption spectra of releasing substances show maxima at 215 and 260 nm and are identical to spectra of non-irradiated cells. The amount of substances increases with dose making up, at the maximal alteration, 180-220%, of the amount releasing from non-irradiated cells. Irradiation with far UV light exceeds by one order that with near UV light. The effect of minimum doses is opposite to the action of high doses: the release of substances from irradiated cells is much less."}
{"id": "PMID:196368", "title": "[Karyological study of the HTR-5 cell line].", "content": "A karyologic study of the human fibroblasts transformed by the SV-40 virus at the level of the 15th subculture shows that this line (HTR-5) consists mainly of cells with a pseudodiploid karyotype. The cells of the investigated line contain marker chromosomes characteristic for this cell culture.", "contents": "[Karyological study of the HTR-5 cell line]. A karyologic study of the human fibroblasts transformed by the SV-40 virus at the level of the 15th subculture shows that this line (HTR-5) consists mainly of cells with a pseudodiploid karyotype. The cells of the investigated line contain marker chromosomes characteristic for this cell culture."}
{"id": "PMID:196373", "title": "[Participation of some nucleotides in regulation of phosphoprotein phosphates activity in rat and chicken myocardium].", "content": "Adenine- and uridine di- and triphosphates (in a 3 mM concentration) increase considerably phosphoprotein phosphatase (PPPase) (EC 3.1.3.16) activity of rat and chicken myocardium homogenates. AMP and Pi are effective inhibitors of the enzyme. The ATP activating effect is also shown in partially purified preparations of rat myocardium PPPase. ATP is able of protecting significantly the enzyme during its thermodenaturation.", "contents": "[Participation of some nucleotides in regulation of phosphoprotein phosphates activity in rat and chicken myocardium]. Adenine- and uridine di- and triphosphates (in a 3 mM concentration) increase considerably phosphoprotein phosphatase (PPPase) (EC 3.1.3.16) activity of rat and chicken myocardium homogenates. AMP and Pi are effective inhibitors of the enzyme. The ATP activating effect is also shown in partially purified preparations of rat myocardium PPPase. ATP is able of protecting significantly the enzyme during its thermodenaturation."}
{"id": "PMID:196374", "title": "[Effect of insulin on activity of carbohydrate metabolism enzymes in loach embryos in early development].", "content": "It is established that in embryos incubated until the early blastula stage in the solution of insulin with addition of cycloheximide or puromycin, there is neither a decrease in the hexokinase and glucose-61 phosphate dehydrogenase activities nor an increase in the phosphofructokinase activity, as it is shown under the influence of insulin only. Puromycin removes an inhibitory effect of insulin on the glucose-6-phosphatase activity, and actinomycin D removes this influence with respect to glucose-6-phosphate dehydrogenase and glucose-6-phosphatase activities. The addition of antibiotics removes inhibition of the hexokinase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase activities by the hormone in the unfertilized eggs as well. Actinomycin D alone inhibits the hexokinase and activates the phosphofructokinase activities in the embryos and eggs, puromycin decreases their hexokinase activity and cycloheximide has the same effect on the glucose-6-phosphatase activity in the embryos only.", "contents": "[Effect of insulin on activity of carbohydrate metabolism enzymes in loach embryos in early development]. It is established that in embryos incubated until the early blastula stage in the solution of insulin with addition of cycloheximide or puromycin, there is neither a decrease in the hexokinase and glucose-61 phosphate dehydrogenase activities nor an increase in the phosphofructokinase activity, as it is shown under the influence of insulin only. Puromycin removes an inhibitory effect of insulin on the glucose-6-phosphatase activity, and actinomycin D removes this influence with respect to glucose-6-phosphate dehydrogenase and glucose-6-phosphatase activities. The addition of antibiotics removes inhibition of the hexokinase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase activities by the hormone in the unfertilized eggs as well. Actinomycin D alone inhibits the hexokinase and activates the phosphofructokinase activities in the embryos and eggs, puromycin decreases their hexokinase activity and cycloheximide has the same effect on the glucose-6-phosphatase activity in the embryos only."}
{"id": "PMID:196375", "title": "[Characteristics of protein kinases from myocardium and their use for studying cAMP content in rat tissues after muscular activity].", "content": "Protein kinase from the bull myocardium tissue was separated by means of the stepped gradient of buffer concentrations on DEAE-cellulose. Sensitivity of the obtained fractions to cAMP was studied. Protein kinase isolated at elution by 0.3 M potassium-phosphate buffer from DEAE-cellulose is less sensitive to cAMP than protein kinase isolated according to Kuo. A decrease in the content of cAMP is established in the tissues of the skeletal muscles and adrenals of rats after long physical loading. No statistically significant changes are found in the level of cAMP under the same conditions in the myocardium and brain tissues.", "contents": "[Characteristics of protein kinases from myocardium and their use for studying cAMP content in rat tissues after muscular activity]. Protein kinase from the bull myocardium tissue was separated by means of the stepped gradient of buffer concentrations on DEAE-cellulose. Sensitivity of the obtained fractions to cAMP was studied. Protein kinase isolated at elution by 0.3 M potassium-phosphate buffer from DEAE-cellulose is less sensitive to cAMP than protein kinase isolated according to Kuo. A decrease in the content of cAMP is established in the tissues of the skeletal muscles and adrenals of rats after long physical loading. No statistically significant changes are found in the level of cAMP under the same conditions in the myocardium and brain tissues."}
{"id": "PMID:196378", "title": "Tissue-cultured head and neck tumors: their use in in vitro assays of immune response.", "content": "Samples of 35 tumors from the head and neck region (25 squamous cell, 2 basal cell, 5 parotid, 3 melanoma, and 1 lymphosarcoma) were cultured after dispersement with either trypsin or collagenase treatment. Growth was established in 14 (40%). Cultured tumor cells were then used as target cells in in vitro assays of patients' cellular and humoral immunity to their own or similar tumors. Preliminary data suggest this may be a reliable method of monitoring responses in patients receiving immunotherapy for head and neck malignancies.", "contents": "Tissue-cultured head and neck tumors: their use in in vitro assays of immune response. Samples of 35 tumors from the head and neck region (25 squamous cell, 2 basal cell, 5 parotid, 3 melanoma, and 1 lymphosarcoma) were cultured after dispersement with either trypsin or collagenase treatment. Growth was established in 14 (40%). Cultured tumor cells were then used as target cells in in vitro assays of patients' cellular and humoral immunity to their own or similar tumors. Preliminary data suggest this may be a reliable method of monitoring responses in patients receiving immunotherapy for head and neck malignancies."}
{"id": "PMID:196384", "title": "Ovarian tumors and related lesions in aged chimpanzees.", "content": "The ovaries of a 48-year-old chimpanzee each contained a large bilateral fibrothecoma. A 39-year-old chimpanzee had two small fibrothecomas in one ovary and a well-differentiated Sertoli-Leydig cell tumor in the other; there also was adenomatous hyperplasia of the endometrium. Both animals had extensive thecal hypertrophy in the ovaries. Thecal hypertrophy might have been a source of excessive estrogen and could have been a partial cause of the ovarian tumors.", "contents": "Ovarian tumors and related lesions in aged chimpanzees. The ovaries of a 48-year-old chimpanzee each contained a large bilateral fibrothecoma. A 39-year-old chimpanzee had two small fibrothecomas in one ovary and a well-differentiated Sertoli-Leydig cell tumor in the other; there also was adenomatous hyperplasia of the endometrium. Both animals had extensive thecal hypertrophy in the ovaries. Thecal hypertrophy might have been a source of excessive estrogen and could have been a partial cause of the ovarian tumors."}
{"id": "PMID:196385", "title": "Encephalomyocarditis virus antibodies in sera from apparently normal pigs.", "content": "Antibodies which neutralise and precipitate encephalomyocarditis virus habe been found in the serum of more than 28 per cent of normal pigs in Britain. Neutralising activity was found in association with several size classes of antibody.", "contents": "Encephalomyocarditis virus antibodies in sera from apparently normal pigs. Antibodies which neutralise and precipitate encephalomyocarditis virus habe been found in the serum of more than 28 per cent of normal pigs in Britain. Neutralising activity was found in association with several size classes of antibody."}
{"id": "PMID:196386", "title": "Experiements with an inactivated hepatitis leptospirosis vaccine in vaccination programmes for dogs.", "content": "A fluid adjuvanted vaccine consisting of inactivated hepatitis virus (iH) and leptospirae antigens (L) was developed. The vaccine (Kavak iHL; Duphar) was tested in several vaccination programmes both alone and in combination with freeze dried measles (M) or distemper (D) vaccines. The results demonstrate that this new vaccine is also effective in pups with maternally derived antibodies, although a second vaccination at 14 weeks of age is recommended to boost the first vaccination. For the booster vaccination either the iHL-vaccine or the liver attenuated hepatitis vaccine (H) can be used.", "contents": "Experiements with an inactivated hepatitis leptospirosis vaccine in vaccination programmes for dogs. A fluid adjuvanted vaccine consisting of inactivated hepatitis virus (iH) and leptospirae antigens (L) was developed. The vaccine (Kavak iHL; Duphar) was tested in several vaccination programmes both alone and in combination with freeze dried measles (M) or distemper (D) vaccines. The results demonstrate that this new vaccine is also effective in pups with maternally derived antibodies, although a second vaccination at 14 weeks of age is recommended to boost the first vaccination. For the booster vaccination either the iHL-vaccine or the liver attenuated hepatitis vaccine (H) can be used."}
{"id": "PMID:196390", "title": "Benign human mammary myoepithelioma.", "content": "A leiomyoma-like, multifocal tumour developed from intraductal papillomatosis in the breast of a 42 year old woman. The spindle-shaped tumour cells were examined by light, electron and polarizing microscopy, which revealed that they originated from immature \"precursor\" myoepithelial cells. The author suggests that the tumour be called \"myoepithelioma\". From the morphological characteristics of the tumour the myoepithelial cells appear to be capable of producing leiomyoma-like benign or malignant tumours. The role that has been attributed by some to the myoepithelial cell in the production of epithelial tumours is problematical, in the light of the present finding.", "contents": "Benign human mammary myoepithelioma. A leiomyoma-like, multifocal tumour developed from intraductal papillomatosis in the breast of a 42 year old woman. The spindle-shaped tumour cells were examined by light, electron and polarizing microscopy, which revealed that they originated from immature \"precursor\" myoepithelial cells. The author suggests that the tumour be called \"myoepithelioma\". From the morphological characteristics of the tumour the myoepithelial cells appear to be capable of producing leiomyoma-like benign or malignant tumours. The role that has been attributed by some to the myoepithelial cell in the production of epithelial tumours is problematical, in the light of the present finding."}
{"id": "PMID:196391", "title": "Electron microscopic study of signet-ring cells in diffuse carcinoma of the human stomach.", "content": "The signet-ring cells seen in gastric carcinoma of the diffuse type were studied by light and electron microscopy. A classification of these cells into Types A, B and C was developed, based on intracellular mucous granules, nuclei and organelles, and be reactions to PAS and Alcian-blue staining. The gradual transition of type A cells to Type B and the subsequent change of Type B to Type C suggest successive stages in maturation. These cells, especially those of Type B, resemble the mucous neck cells of the corpus and the glands of the pylorus.", "contents": "Electron microscopic study of signet-ring cells in diffuse carcinoma of the human stomach. The signet-ring cells seen in gastric carcinoma of the diffuse type were studied by light and electron microscopy. A classification of these cells into Types A, B and C was developed, based on intracellular mucous granules, nuclei and organelles, and be reactions to PAS and Alcian-blue staining. The gradual transition of type A cells to Type B and the subsequent change of Type B to Type C suggest successive stages in maturation. These cells, especially those of Type B, resemble the mucous neck cells of the corpus and the glands of the pylorus."}
{"id": "PMID:196404", "title": "[Glyconeogenesis in rat liver in thermal burns].", "content": "Processes of glyconeogenesis were increased in rats, subjected to burns. This was corroborated by activation of the glyconeogenesis key enzymes (phosphoenol pyruvate carboxylase and fructose diphosphatase) as well as by the increased incorporation of 14C-amino acids into liver glycogen. The activation of glyconeogenesis had an adaptational importance under burns; it was directed towards the compensation of glycogen content in liver tissue and maintaining of sugar level in blood.", "contents": "[Glyconeogenesis in rat liver in thermal burns]. Processes of glyconeogenesis were increased in rats, subjected to burns. This was corroborated by activation of the glyconeogenesis key enzymes (phosphoenol pyruvate carboxylase and fructose diphosphatase) as well as by the increased incorporation of 14C-amino acids into liver glycogen. The activation of glyconeogenesis had an adaptational importance under burns; it was directed towards the compensation of glycogen content in liver tissue and maintaining of sugar level in blood."}
{"id": "PMID:196405", "title": "[Nature of the proteinase activated by the contact factor in human blood plasma].", "content": "The nature of protamine splitting proteinase, which was formed after treatment of human blood plasma by kaolin or silicone (aerosile), was studied. The activated enzyme did not exhibite the properties of thrombin and plasmin in reactions with specific substrates. Kyninogenic, TAME (N-tosyl-d-,l-arginine methyl ester)-esterase and protamine splitting activities were inherent in the proteinase; these properties enabled to group the enzyme with blood kallikreins. The purified preparations of human blood plasma kallikrein hydrolyzed protamine sulphate even at 10 mcg/ml concentration. alpha2-macroglobulin inhibited the protamine splitting activity of the plasma kallikrein.", "contents": "[Nature of the proteinase activated by the contact factor in human blood plasma]. The nature of protamine splitting proteinase, which was formed after treatment of human blood plasma by kaolin or silicone (aerosile), was studied. The activated enzyme did not exhibite the properties of thrombin and plasmin in reactions with specific substrates. Kyninogenic, TAME (N-tosyl-d-,l-arginine methyl ester)-esterase and protamine splitting activities were inherent in the proteinase; these properties enabled to group the enzyme with blood kallikreins. The purified preparations of human blood plasma kallikrein hydrolyzed protamine sulphate even at 10 mcg/ml concentration. alpha2-macroglobulin inhibited the protamine splitting activity of the plasma kallikrein."}
{"id": "PMID:196406", "title": "[Biochemical heterogeneity of mitochondria from mucosa of rat small intestine].", "content": "Mitochondria from mucosa of rat small intestine were separated (0-11% gradient of ficoll) into fractions, differing by the content of protein, DNA and cytochrome a+a3 as well as by the respiratory activity and the activity of succinate- and NADH-dehydrogenases. Content of DNA and cytochrome a+c was shown to be increased in \"heavy\" mitochondrial fractions. Mitochondria od \"midle\" fractions possessed the highest functional activity. The data obtained suggest that the mitochondrial preparations are not contaminated by other cytoplasmic structures; they were also not impaired during isolation and fractionation. The activity of RNA and DNA synthesis in vivo and distribution of labelled mitochondrial RNA and DNA in the fractions were studied. The possible relation of mitochondrial heterogeneity to, their biogenesis is discussed.", "contents": "[Biochemical heterogeneity of mitochondria from mucosa of rat small intestine]. Mitochondria from mucosa of rat small intestine were separated (0-11% gradient of ficoll) into fractions, differing by the content of protein, DNA and cytochrome a+a3 as well as by the respiratory activity and the activity of succinate- and NADH-dehydrogenases. Content of DNA and cytochrome a+c was shown to be increased in \"heavy\" mitochondrial fractions. Mitochondria od \"midle\" fractions possessed the highest functional activity. The data obtained suggest that the mitochondrial preparations are not contaminated by other cytoplasmic structures; they were also not impaired during isolation and fractionation. The activity of RNA and DNA synthesis in vivo and distribution of labelled mitochondrial RNA and DNA in the fractions were studied. The possible relation of mitochondrial heterogeneity to, their biogenesis is discussed."}
{"id": "PMID:196407", "title": "[Use of circadian rhythms for analysis of the interrelationships between the concentration of glucocorticoids in the blood and the activity of key enzymes for gluconeogenesis in the liver and kidney of rats].", "content": "Circadian rhythms of alterations in content of 11-hydroxycorticosteroids and glucose in blood as well as in the activity of phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase in liver and kidney tissues were studied under normal and inverted luminous regimens in summer and winter seasons. These patterns were distinctly altered depending on circadian rhythms in the above-mentioned conditions. The maximal content of 11-hydroxycorticosteroids in blood did not correlate with the highest activity of the gluconeogenesis key enzymes in the periods studied. Daily alterations in the activity of phosphoemolpyruvate carboxykinase were shown to be similar to that of the fructose-1,6-diphosphatase in various tissues at different seasons. But glucose-6-phosphatase differed distinctly from these enzymes by the daily rhythm of activity. This suggests that glucose-6-phosphatase has the other mechanism for regulation of its daily rhythm.", "contents": "[Use of circadian rhythms for analysis of the interrelationships between the concentration of glucocorticoids in the blood and the activity of key enzymes for gluconeogenesis in the liver and kidney of rats]. Circadian rhythms of alterations in content of 11-hydroxycorticosteroids and glucose in blood as well as in the activity of phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase and glucose-6-phosphatase in liver and kidney tissues were studied under normal and inverted luminous regimens in summer and winter seasons. These patterns were distinctly altered depending on circadian rhythms in the above-mentioned conditions. The maximal content of 11-hydroxycorticosteroids in blood did not correlate with the highest activity of the gluconeogenesis key enzymes in the periods studied. Daily alterations in the activity of phosphoemolpyruvate carboxykinase were shown to be similar to that of the fructose-1,6-diphosphatase in various tissues at different seasons. But glucose-6-phosphatase differed distinctly from these enzymes by the daily rhythm of activity. This suggests that glucose-6-phosphatase has the other mechanism for regulation of its daily rhythm."}
{"id": "PMID:196408", "title": "[Stimulating effect of glucagon and theophylline on the activity of rat liver betamine-homocysteine-methyltransferase. Role of cyclic adenosine-3',5'-monophosphate].", "content": "Effect of glucagon, theophylline, NaF and cyclic 3',5'-AMP on the activity of betaine-homocysteine-methyl transferase (BHMT) was studied in homogenates of rat liver tissue. Intraperitoneal administration of theophylline into adult rats increased the BHMT activity in liver tissue. After administration of theophylline the BHMT activity was distinctly increased in liver tissue within 2 hrs, approaching the maximal value within 3 hrs after which it decreased quickly up to 5-6 hrs. Intraperitoneal administration of glucagon into adult rats also increased the BHMT activity; theophylline, administered simultaneously with glucagon, potentiated the effect of the latter on the BHMT activity in liver tissue. Administration of glucagon into rat embryos 1-2 days before the birth was accompanied by a 2-fold increase in the BHMT activity. In the in vitro experiments theophylline (10(-6)-10(-5) M) showed the stimulating effect on the liver tissue BHMT activity. Dibutyryl adenosine-3,5'-cyclic phosphate and NaF caused the variable effect on the BHMT activity in liver tissue of adult rats. Administration of cyclic-3',5'-AMP (5 mg per 100 g of body weight) decreased the BHMT activity in liver tissue mitochondria and increased 2.5-fold the enzyme activity in cytosole.", "contents": "[Stimulating effect of glucagon and theophylline on the activity of rat liver betamine-homocysteine-methyltransferase. Role of cyclic adenosine-3',5'-monophosphate]. Effect of glucagon, theophylline, NaF and cyclic 3',5'-AMP on the activity of betaine-homocysteine-methyl transferase (BHMT) was studied in homogenates of rat liver tissue. Intraperitoneal administration of theophylline into adult rats increased the BHMT activity in liver tissue. After administration of theophylline the BHMT activity was distinctly increased in liver tissue within 2 hrs, approaching the maximal value within 3 hrs after which it decreased quickly up to 5-6 hrs. Intraperitoneal administration of glucagon into adult rats also increased the BHMT activity; theophylline, administered simultaneously with glucagon, potentiated the effect of the latter on the BHMT activity in liver tissue. Administration of glucagon into rat embryos 1-2 days before the birth was accompanied by a 2-fold increase in the BHMT activity. In the in vitro experiments theophylline (10(-6)-10(-5) M) showed the stimulating effect on the liver tissue BHMT activity. Dibutyryl adenosine-3,5'-cyclic phosphate and NaF caused the variable effect on the BHMT activity in liver tissue of adult rats. Administration of cyclic-3',5'-AMP (5 mg per 100 g of body weight) decreased the BHMT activity in liver tissue mitochondria and increased 2.5-fold the enzyme activity in cytosole."}
{"id": "PMID:196412", "title": "[Content of the components of the adenylic acid system in solid and ascitic tumors in the liver of experimental animals].", "content": "The authors report the results of separate determination of the concentration of free adenine nucleotides (ATP, ADP, AMP) in tumors, intact animals liver, and tumor-bearing animals liver. In Zajdela ascites hepatoma, ascites tumor NKly and solid lymphosarcoma, solid hepatomas 46 and 22 A the amount of ATP and ADP was found to be markedly reduced compared with their content in the liver. The ratio ATP/ADP is increased in ascites cells of tumor NKly, Zaidela hepatoma and lymphosarcoma and is decreased in solid hepatoma 46 and 22 A. Cell energy potential, calculated on the basis of ATP ratio to a sum of adenine-nucleotides, is also increased in ascites cells of tumor NKly, Zaidela hepatoma and is diminished or remains unchanged in hepatoma 46 or 22A. Cell energy charge is increased in tumor NKly, Zajdela hepatoma, lymphosarcoma and is decreased in solid hepatoma 46 and 22A.", "contents": "[Content of the components of the adenylic acid system in solid and ascitic tumors in the liver of experimental animals]. The authors report the results of separate determination of the concentration of free adenine nucleotides (ATP, ADP, AMP) in tumors, intact animals liver, and tumor-bearing animals liver. In Zajdela ascites hepatoma, ascites tumor NKly and solid lymphosarcoma, solid hepatomas 46 and 22 A the amount of ATP and ADP was found to be markedly reduced compared with their content in the liver. The ratio ATP/ADP is increased in ascites cells of tumor NKly, Zaidela hepatoma and lymphosarcoma and is decreased in solid hepatoma 46 and 22 A. Cell energy potential, calculated on the basis of ATP ratio to a sum of adenine-nucleotides, is also increased in ascites cells of tumor NKly, Zaidela hepatoma and is diminished or remains unchanged in hepatoma 46 or 22A. Cell energy charge is increased in tumor NKly, Zajdela hepatoma, lymphosarcoma and is decreased in solid hepatoma 46 and 22A."}
{"id": "PMID:196413", "title": "Intensive plasmapheresis as a risk factor for arteriosclerotic cardiovascular disease?", "content": "Recent studies suggest that the analogy between intensive plasmapheresis and the nephrotic syndrome with respect to plasma protein loss includes events which are generally recognized as risk factors for the development of arteriosclerotic cardiovascular disease. Experimental nephrosis and plasmapheresis alike increase the synthesis of very low density and low density lipoproteins in response to the hypoproteinemic stimulation of plasma protein synthesis. During electrophoresis, these lipoproteins move with the alpha2- and beta-globulins, and the serum levels of these fractions are often elevated in humans subjected to intensive plasmapheresis. Hyperlipoproteinemias of the alpha2- and beta-types are recognized risk factors in the genesis of arteriosclerosis. Another such factor appears to be an increased synthesis of fibrinogen. This protein enhances plasma viscosity and red cell aggregation and may play a role in myocardial infarction. Intensive plasmapheresis thus not only creates an unphysiological and partly depletional state; it is also, like the nephrotic syndrome, capable of producing surplus abnormalities of plasma constituents with a potential for delayed, insidious injury.", "contents": "Intensive plasmapheresis as a risk factor for arteriosclerotic cardiovascular disease? Recent studies suggest that the analogy between intensive plasmapheresis and the nephrotic syndrome with respect to plasma protein loss includes events which are generally recognized as risk factors for the development of arteriosclerotic cardiovascular disease. Experimental nephrosis and plasmapheresis alike increase the synthesis of very low density and low density lipoproteins in response to the hypoproteinemic stimulation of plasma protein synthesis. During electrophoresis, these lipoproteins move with the alpha2- and beta-globulins, and the serum levels of these fractions are often elevated in humans subjected to intensive plasmapheresis. Hyperlipoproteinemias of the alpha2- and beta-types are recognized risk factors in the genesis of arteriosclerosis. Another such factor appears to be an increased synthesis of fibrinogen. This protein enhances plasma viscosity and red cell aggregation and may play a role in myocardial infarction. Intensive plasmapheresis thus not only creates an unphysiological and partly depletional state; it is also, like the nephrotic syndrome, capable of producing surplus abnormalities of plasma constituents with a potential for delayed, insidious injury."}
{"id": "PMID:196409", "title": "[1 of the possible causes of an increase in acid hydrolase activity in homogenates of heart muscle following myocardial infarct].", "content": "A \"free\" activity of acidic hydrolases (acidic phosphatase, acidic ribonuclease and cathepsin D) was increased in homogenates of dog heart muscle with simultaneous decrease of the enzymes activity in the fraction enriched by lysosomes, within 4-5 hrs after ligation of the descending ramus of sinister mitral artery. The adenylate cyclase activity and content of c-AMP were decreased as compared with unaffected part of myocardium. The data obtained suggest that the decrease of the c-AMP content in the impaired region caused a labilization of lysosomal membranes and the secretion of acidic hydrolases into cell cytoplasm.", "contents": "[1 of the possible causes of an increase in acid hydrolase activity in homogenates of heart muscle following myocardial infarct]. A \"free\" activity of acidic hydrolases (acidic phosphatase, acidic ribonuclease and cathepsin D) was increased in homogenates of dog heart muscle with simultaneous decrease of the enzymes activity in the fraction enriched by lysosomes, within 4-5 hrs after ligation of the descending ramus of sinister mitral artery. The adenylate cyclase activity and content of c-AMP were decreased as compared with unaffected part of myocardium. The data obtained suggest that the decrease of the c-AMP content in the impaired region caused a labilization of lysosomal membranes and the secretion of acidic hydrolases into cell cytoplasm."}
{"id": "PMID:196419", "title": "Electron microscopic studies on the formation of vesicular bodies during cell wall degradation and regeneration in yeast.", "content": "Vesicular bodies are observed during enzymatic degradation of the yeast cell wall and in the course of wall regeneration. In both cases various types of vesicles are formed and exocytated by different mechanisms. They are characterized cytochemically and their possible role in cell wall regeneration is discussed.", "contents": "Electron microscopic studies on the formation of vesicular bodies during cell wall degradation and regeneration in yeast. Vesicular bodies are observed during enzymatic degradation of the yeast cell wall and in the course of wall regeneration. In both cases various types of vesicles are formed and exocytated by different mechanisms. They are characterized cytochemically and their possible role in cell wall regeneration is discussed."}
{"id": "PMID:196421", "title": "[Controlled clinical study of the herpes antigens LUPIDON H and LUPIDON G].", "content": "Results gained in a placebo-controlled, clinical double-blind study with the Herpes antigens LUPIDON H and Lupidon G are reported. Due to treatment with LUPIDON H or LUPIDON G a cure or a more soothed course of the disease and among the indicated effects a prolongation in length of the intervals during which no relapses occurred could be observed with regard to about 80% of all the patients concerned. In opposition to the mentioned effectiveness the treatment success becoming evident after the administration of Placebo under equal test conditions was only evaluated with a rate complying to approximately 30%. The difference determined at those investigations with reference to the efficacy of LUPIDON (80%) in comparison with Placebo (30%) is statistically significant. This outcome confirms the results already observed hitherto in open clinical investigations by other examiners whose findings, too, ascribed to LUPIDON a favourable influence on Herpes simplex diseases in about 80% of treatment cases.", "contents": "[Controlled clinical study of the herpes antigens LUPIDON H and LUPIDON G]. Results gained in a placebo-controlled, clinical double-blind study with the Herpes antigens LUPIDON H and Lupidon G are reported. Due to treatment with LUPIDON H or LUPIDON G a cure or a more soothed course of the disease and among the indicated effects a prolongation in length of the intervals during which no relapses occurred could be observed with regard to about 80% of all the patients concerned. In opposition to the mentioned effectiveness the treatment success becoming evident after the administration of Placebo under equal test conditions was only evaluated with a rate complying to approximately 30%. The difference determined at those investigations with reference to the efficacy of LUPIDON (80%) in comparison with Placebo (30%) is statistically significant. This outcome confirms the results already observed hitherto in open clinical investigations by other examiners whose findings, too, ascribed to LUPIDON a favourable influence on Herpes simplex diseases in about 80% of treatment cases."}
{"id": "PMID:196422", "title": "Effect of different amino acids on the phosphatase system of an ectoparasite: Poecilobdella granulosa.", "content": "Inhibitory effect of different amino acids (L-phenylalanine, L-tryptophan, L-tyrosine, L-histidine-monochloride and L-arginine) on the phosphatase system of the brain, ventral nerve cord, stomach and intestine of the Indian medicinal leech Poecilobdella granulosa, was observed to be substrate, tissue, and inhibitor-specific. Most fascinating observation recorded was the activation of alkaline phosphatase of stomach and intestine by certain amino acids at low concentrations. This has been correlated with the sanguivorous habit of leeches.", "contents": "Effect of different amino acids on the phosphatase system of an ectoparasite: Poecilobdella granulosa. Inhibitory effect of different amino acids (L-phenylalanine, L-tryptophan, L-tyrosine, L-histidine-monochloride and L-arginine) on the phosphatase system of the brain, ventral nerve cord, stomach and intestine of the Indian medicinal leech Poecilobdella granulosa, was observed to be substrate, tissue, and inhibitor-specific. Most fascinating observation recorded was the activation of alkaline phosphatase of stomach and intestine by certain amino acids at low concentrations. This has been correlated with the sanguivorous habit of leeches."}
{"id": "PMID:196423", "title": "Comparative histochemical observations on the excretory system of helminth parasites.", "content": "The excretory canals of Ascaridia galli (Nematoda) and the protonephridial ducts of Cotylophoron cotylophorum (Trematoda) and Raillietina cesticillus (Cestoda) have been studied with regard to the histochemical localization of lipids, carbohydrates and hydrolytic enzymes. Distinct excretory organs are absent in the acanthocephalan Centrorhynchus corvi. Triglycerides, phospholipids and lipoproteins are seen in association with the wall of excretory canals of A. galli and R. cesticillus, and phospholipids and lipoproteins at the corresponding site in C. cotylophorum. The physiological significance of lipids in association with excretion of substances has been discussed. Low molecular weight glycogen is present in the lumen of excretory canal of A. galli but not in other worms. The common feature of the excretory canals is the presence of enzyme activities of nonspecific alkaline phosphatase and Mg2+-dependent ATPase. Activity of acid phosphatase is seen only in the excretory canals of A. galli. Glucose-6-phosphatase is present in A. galli and C. cotylophorum and absent in R. cesticillus. Weak reaction of 5'-nucleotidase is present in the excretory canals of helminth species studied here. The role of these enzymes in transportation of substances across the wall of excretory canals and also in ionic regulation has been discussed in detail.", "contents": "Comparative histochemical observations on the excretory system of helminth parasites. The excretory canals of Ascaridia galli (Nematoda) and the protonephridial ducts of Cotylophoron cotylophorum (Trematoda) and Raillietina cesticillus (Cestoda) have been studied with regard to the histochemical localization of lipids, carbohydrates and hydrolytic enzymes. Distinct excretory organs are absent in the acanthocephalan Centrorhynchus corvi. Triglycerides, phospholipids and lipoproteins are seen in association with the wall of excretory canals of A. galli and R. cesticillus, and phospholipids and lipoproteins at the corresponding site in C. cotylophorum. The physiological significance of lipids in association with excretion of substances has been discussed. Low molecular weight glycogen is present in the lumen of excretory canal of A. galli but not in other worms. The common feature of the excretory canals is the presence of enzyme activities of nonspecific alkaline phosphatase and Mg2+-dependent ATPase. Activity of acid phosphatase is seen only in the excretory canals of A. galli. Glucose-6-phosphatase is present in A. galli and C. cotylophorum and absent in R. cesticillus. Weak reaction of 5'-nucleotidase is present in the excretory canals of helminth species studied here. The role of these enzymes in transportation of substances across the wall of excretory canals and also in ionic regulation has been discussed in detail."}
{"id": "PMID:196424", "title": "Effect of decerebration on the enzymatic system of stomach and intestine of Indian cattle leech, Poecilobdella granulosa.", "content": "Experiments on decerebration have brought to light an interesting inverse relationship between the phosphatases of two digestive components, at least up to a week. With the activation of all the gastric phosphatases, intestinal phosphatases are inhibited. This has been correlated with metabolic metameric control in leech.", "contents": "Effect of decerebration on the enzymatic system of stomach and intestine of Indian cattle leech, Poecilobdella granulosa. Experiments on decerebration have brought to light an interesting inverse relationship between the phosphatases of two digestive components, at least up to a week. With the activation of all the gastric phosphatases, intestinal phosphatases are inhibited. This has been correlated with metabolic metameric control in leech."}
{"id": "PMID:196425", "title": "[An additional nerv-lesion in cases of total hip replacement (author's transl)].", "content": "Report of early secundary paresis of the sciatic nerve after the implantation of a total artificial hip-joint by the dorso-lateral exposure. The paresis is caused by a cicatrical stenosis of the nerve following a peri- and intranerval bleeding.", "contents": "[An additional nerv-lesion in cases of total hip replacement (author's transl)]. Report of early secundary paresis of the sciatic nerve after the implantation of a total artificial hip-joint by the dorso-lateral exposure. The paresis is caused by a cicatrical stenosis of the nerve following a peri- and intranerval bleeding."}
{"id": "PMID:196452", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. X. Influence of substrate concentration (author's transl)].", "content": "The tripolyphosphatase activity of comminuted bovine muscle increased with rising substrate concentration (up to 0.8% tripolyphosphate in presence of 2% NaCl). Addition of NaCl increased the maximum velocity (Vmax) of the enzymatic hydrolysis, determined by Lineweaver-Burk plots. From the results it is concluded that the product-dissociation is the rate-limiting step in the breakdown of tripolyphosphate. Increasing diphosphate concentrations caused only a small increase in the diphosphatase activity of minced tissue. Addition of NaCl lowered the Vmax of the diphosphatase reaction.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. X. Influence of substrate concentration (author's transl)]. The tripolyphosphatase activity of comminuted bovine muscle increased with rising substrate concentration (up to 0.8% tripolyphosphate in presence of 2% NaCl). Addition of NaCl increased the maximum velocity (Vmax) of the enzymatic hydrolysis, determined by Lineweaver-Burk plots. From the results it is concluded that the product-dissociation is the rate-limiting step in the breakdown of tripolyphosphate. Increasing diphosphate concentrations caused only a small increase in the diphosphatase activity of minced tissue. Addition of NaCl lowered the Vmax of the diphosphatase reaction."}
{"id": "PMID:196453", "title": "Simple mathematical deductions in the seroepidemiology of viral infections. I. Herpesvirus group (herpesvirus hominis, varicella-zoster virus, cytomegalovris, Epstein-Barr-Virus).", "content": "Large samples of nonselected persons collected in South-West Germnay were investigated for the prevalence of serum antibodies to the human Herpesviruses HSV, VZV, CMV and EBV. According to \"catalytic models\", which compare the infection spread to simple chemical reactions of molecules, a mathematical approximation of the serum surveys was performed. Through a new deduction of the exponential function y = k (l - e-r+) a simple way was found to estimate the annual attack rates in percent of the susceptible, seronegative people. While it was possible to represent the prevalence of serum antibodies to VZV by a continuous curve, a biphasic curve to the antibody prevalence rates in the epidemiology of the other Herpesviruses proved to be more adequate indicating changes in hormonal balance and social behaviour. The use of the epidemiologic parameters k and r for the characterization of the test sensitivity was examined for CMV. By evaluation of the mean antibody titres to CMV, HSV, and EBV throughout different age groups, information about the reactivation of the Herpesvirus diseases could be obtained.", "contents": "Simple mathematical deductions in the seroepidemiology of viral infections. I. Herpesvirus group (herpesvirus hominis, varicella-zoster virus, cytomegalovris, Epstein-Barr-Virus). Large samples of nonselected persons collected in South-West Germnay were investigated for the prevalence of serum antibodies to the human Herpesviruses HSV, VZV, CMV and EBV. According to \"catalytic models\", which compare the infection spread to simple chemical reactions of molecules, a mathematical approximation of the serum surveys was performed. Through a new deduction of the exponential function y = k (l - e-r+) a simple way was found to estimate the annual attack rates in percent of the susceptible, seronegative people. While it was possible to represent the prevalence of serum antibodies to VZV by a continuous curve, a biphasic curve to the antibody prevalence rates in the epidemiology of the other Herpesviruses proved to be more adequate indicating changes in hormonal balance and social behaviour. The use of the epidemiologic parameters k and r for the characterization of the test sensitivity was examined for CMV. By evaluation of the mean antibody titres to CMV, HSV, and EBV throughout different age groups, information about the reactivation of the Herpesvirus diseases could be obtained."}
{"id": "PMID:196454", "title": "Simple mathematical deductions in the seroepidemiology of viral infections. II. (Para) myxoviruses (measles, mumps, influenza B), rubella, enteroviruses (polio, coxsackie B), adenoviruses, and mycoplasma pneumoniae.", "content": "Large samples of nonselected persons collected in South-West Germany were investigated for the prevalence of serum antibodies to Poliovirus 1-3 and Coxsackievirus B 1-5 (neutralisation test), to Measles, Rubella, and Mumps (hemagglutination inhibition test), Mumps, Influenza B, Adenovirus, and Mycoplasma pneumoniae (complement-fixation test). According to \"catalytic models\", which compare the infection spread to simple chemical reactions of molecules as self-limiting procedures, a mathematical approximation of the serum surveys was performed. By the use of only two parameters it became possible to calculate the annual attack rates (without regard of age group arrangement and test sensibility), to construct \"true\" epidemic curves, and to estimate the persistence of humoral immunity in the population investigated for NT and HIT antibodies.", "contents": "Simple mathematical deductions in the seroepidemiology of viral infections. II. (Para) myxoviruses (measles, mumps, influenza B), rubella, enteroviruses (polio, coxsackie B), adenoviruses, and mycoplasma pneumoniae. Large samples of nonselected persons collected in South-West Germany were investigated for the prevalence of serum antibodies to Poliovirus 1-3 and Coxsackievirus B 1-5 (neutralisation test), to Measles, Rubella, and Mumps (hemagglutination inhibition test), Mumps, Influenza B, Adenovirus, and Mycoplasma pneumoniae (complement-fixation test). According to \"catalytic models\", which compare the infection spread to simple chemical reactions of molecules as self-limiting procedures, a mathematical approximation of the serum surveys was performed. By the use of only two parameters it became possible to calculate the annual attack rates (without regard of age group arrangement and test sensibility), to construct \"true\" epidemic curves, and to estimate the persistence of humoral immunity in the population investigated for NT and HIT antibodies."}
{"id": "PMID:196455", "title": "[Laboratory procedures in adenoviruses. IV. The influence of antiglobulin and complement on neutralization and hemagglutination-inhibition (author's transl)].", "content": "The neutralization of adenovirus 3,7, and 19 by rabbit antisera is enhanced by additional application of antirabbit globulin. All sera investigated, obtained early or late after the start of immunization, showed two- to sixfold titer rises. Complement also enhances the neutralization; the titer is raised to a greater extent in early than in late sera. To achieve maximal effects, antiglobulin and complement had to be used in fairly high concentration (ca. 10%). In hemagglutination-inhibition the same set of sera showed a titer increase mediated by anti-rabbit globulin (mostly by the factor 2 to 4), while complement was without influence. The neutralization titer of human sera from patients with adenovirus infections, as opposed to the rabbit antisera, was only slightly increased by addition of anti-human globulin or complement. These reagents had likewise negligible influence on the hemagglutination-inhibition of adenovirus 8 by human sera.", "contents": "[Laboratory procedures in adenoviruses. IV. The influence of antiglobulin and complement on neutralization and hemagglutination-inhibition (author's transl)]. The neutralization of adenovirus 3,7, and 19 by rabbit antisera is enhanced by additional application of antirabbit globulin. All sera investigated, obtained early or late after the start of immunization, showed two- to sixfold titer rises. Complement also enhances the neutralization; the titer is raised to a greater extent in early than in late sera. To achieve maximal effects, antiglobulin and complement had to be used in fairly high concentration (ca. 10%). In hemagglutination-inhibition the same set of sera showed a titer increase mediated by anti-rabbit globulin (mostly by the factor 2 to 4), while complement was without influence. The neutralization titer of human sera from patients with adenovirus infections, as opposed to the rabbit antisera, was only slightly increased by addition of anti-human globulin or complement. These reagents had likewise negligible influence on the hemagglutination-inhibition of adenovirus 8 by human sera."}
{"id": "PMID:196456", "title": "[Fecal flora of man. V. communication: The fluctuation of the fecal flora of the healthy adult (author's transl)].", "content": "Seven fecal specimens from each of healthy persons, aged 25 to 42 years, during the period of 2 months were analyzed to obtain the knowledge on the day-to-day variation in the same person and the person-to-person variation. Irrespective of individuals, bacteroidaceae, catenabacteria (eubacteria and strict anaerobic lactobacilli), peptostreptococci (anaerobic gram positive cocci) and bifidobacteria constituted the predominant flora. Spirillaceae, megasphaerae and clostridia (except Cl. perfringens) were also found as predominant flora in specific individuals. In all cases, enterobacteria and streptococci constitute the accompanying flora. In addition, veillonallae and lactobacilli were found as predominant flora in most cases. The remaining flora, consisting of Cl. perfringens, staphylococci and yeast, occurred occasionally in low numbers. With regard to the composition of the fecal flora of each person, a great individual variation was recognized and confirmed statistically. Each person had a characteristic fecal flora. In the same person, the numbers of bacteria of the predominating flora were over a 2 months period relatively constant. On the other hand, a great day-to-day variation in the numbers of bacteria of the accompanying flora as well as the remaining flora was demonstrated.", "contents": "[Fecal flora of man. V. communication: The fluctuation of the fecal flora of the healthy adult (author's transl)]. Seven fecal specimens from each of healthy persons, aged 25 to 42 years, during the period of 2 months were analyzed to obtain the knowledge on the day-to-day variation in the same person and the person-to-person variation. Irrespective of individuals, bacteroidaceae, catenabacteria (eubacteria and strict anaerobic lactobacilli), peptostreptococci (anaerobic gram positive cocci) and bifidobacteria constituted the predominant flora. Spirillaceae, megasphaerae and clostridia (except Cl. perfringens) were also found as predominant flora in specific individuals. In all cases, enterobacteria and streptococci constitute the accompanying flora. In addition, veillonallae and lactobacilli were found as predominant flora in most cases. The remaining flora, consisting of Cl. perfringens, staphylococci and yeast, occurred occasionally in low numbers. With regard to the composition of the fecal flora of each person, a great individual variation was recognized and confirmed statistically. Each person had a characteristic fecal flora. In the same person, the numbers of bacteria of the predominating flora were over a 2 months period relatively constant. On the other hand, a great day-to-day variation in the numbers of bacteria of the accompanying flora as well as the remaining flora was demonstrated."}
{"id": "PMID:196457", "title": "[Pulmonary injury of mice produced by chronically peroral treatment with different substances (author's transl)].", "content": "Authors treated mice chronically peroral with microtoxical doses of paraquate, chromiumsulphate, berylliumsulphate and cadmiumsulphate. It becames evident, that the questioned manner of treatment causes a damage of the lungs. It develops an infiltration in the lungtissue, respectively it comes into being a great pulmonary proliferation of cells. Authors emphasize the fact, that the described pathohistological lesion of the lung develops in that case if the poisoning occurs peroral. If the above mentioned phenomenon comes into being on man similarly pneumophthiseology respectively the hygiene enriches with a new problem, with damages of the lungs produced by chemical substances dosed chronically peroral in very small quantity.", "contents": "[Pulmonary injury of mice produced by chronically peroral treatment with different substances (author's transl)]. Authors treated mice chronically peroral with microtoxical doses of paraquate, chromiumsulphate, berylliumsulphate and cadmiumsulphate. It becames evident, that the questioned manner of treatment causes a damage of the lungs. It develops an infiltration in the lungtissue, respectively it comes into being a great pulmonary proliferation of cells. Authors emphasize the fact, that the described pathohistological lesion of the lung develops in that case if the poisoning occurs peroral. If the above mentioned phenomenon comes into being on man similarly pneumophthiseology respectively the hygiene enriches with a new problem, with damages of the lungs produced by chemical substances dosed chronically peroral in very small quantity."}
{"id": "PMID:196459", "title": "[Detoxification of staphylococcal-enterotoxin B in water (author's transl)].", "content": "Staphylococcal enterotoxin B contaminated water has been detoxified with calcium hypochlorite used in the water treatment procedure which is available now in order to get drinking water from surface water in emergency cases. Changes in toxin-activity were measured serologically by agar-gel-immuno-precipitation as well as biologically by the \"monkey-feeding test\" with young macaca mulatta. With an initial concentration of 50 ppm chlorine in tap water resp. 200 ppm in native surface water concentrations of toxin up to 40 fold average emetic dose of rhesus monkey could be inactivated safely. It was pointed out an obvious conformity between precipitation test and monkey-feeding test. The clinical efficiency of SEB on rhesus monkeys has been investigated and discussed subsequently.", "contents": "[Detoxification of staphylococcal-enterotoxin B in water (author's transl)]. Staphylococcal enterotoxin B contaminated water has been detoxified with calcium hypochlorite used in the water treatment procedure which is available now in order to get drinking water from surface water in emergency cases. Changes in toxin-activity were measured serologically by agar-gel-immuno-precipitation as well as biologically by the \"monkey-feeding test\" with young macaca mulatta. With an initial concentration of 50 ppm chlorine in tap water resp. 200 ppm in native surface water concentrations of toxin up to 40 fold average emetic dose of rhesus monkey could be inactivated safely. It was pointed out an obvious conformity between precipitation test and monkey-feeding test. The clinical efficiency of SEB on rhesus monkeys has been investigated and discussed subsequently."}
{"id": "PMID:196464", "title": "Studies on cytologic characteristics of mammary aspiration smears based on histologic types.", "content": "Cytologic findings of aspiration smears from 146 histologically confirmed mammary were analyzed in this paper. High cellularity, dispersal of cells in the smears and enlarged nuclei of more than 20 mu in major axis were considered to be useful key points to distinguish carcinoma from benign lesions. Irregular piling, variable nuclear shape, cellular fusion and cytoplasmic inclusions were other common findings in cancer specimens and were scarcely noticed in benign cases. However, in some papillotubular carcinomas the above mentioned characteristics were not so dominant. Scirrhous carcinomas sometimes presented small nuclei in the smears. In some fibroadenomas, the smears were occasionally very cellular and revealed dipersal of cells.", "contents": "Studies on cytologic characteristics of mammary aspiration smears based on histologic types. Cytologic findings of aspiration smears from 146 histologically confirmed mammary were analyzed in this paper. High cellularity, dispersal of cells in the smears and enlarged nuclei of more than 20 mu in major axis were considered to be useful key points to distinguish carcinoma from benign lesions. Irregular piling, variable nuclear shape, cellular fusion and cytoplasmic inclusions were other common findings in cancer specimens and were scarcely noticed in benign cases. However, in some papillotubular carcinomas the above mentioned characteristics were not so dominant. Scirrhous carcinomas sometimes presented small nuclei in the smears. In some fibroadenomas, the smears were occasionally very cellular and revealed dipersal of cells."}
{"id": "PMID:196468", "title": "Thyroid function and plasma cyclic AMP response to intravenous glucagon.", "content": "The glucagon stimulated increase in plasma cyclic AMP has been studied in 17 healthy subjects, in 13 hyperthyroid and in 14 hypothyroid patients. Six hyperthyroid and 2 hypothyroid patients were re-investigated after at least 15 months of treatment. The results show: 1) The glucagon stimulated cyclic AMP response is significantly increased in hyperthyroid patients considered as a group, and is reduced in patients with hypothyroidism. 2) Three hyperthyroid and 4 hypothyroid patients showed a normal response to iv glucagon, indicating that the plasma cyclic AMP response to iv glucagon is not a sensitive test for the evaluation of peripheral thyroid states. This suggests that the effects of thyroid hormones in the liver does not necessarily follow the effects in other tissues. 3) Re-investigation of treated patients showed that the cyclic AMP response can be normalized by treatment, both in hyperthyroidism and hypothyroidism. However, in patients treated for hyperthyroidism a hyper-response to glucagon can continue after blood levels of thyroid hormones are reduced to normal. This suggests an inertia in the loss of the hyper-response to glucagon, once a hyperfunction has been induced. A similar inertia in the loss of glucagon sensitivity in hypothyroidism could explain the large number of normal tests in hypothyroid patients.", "contents": "Thyroid function and plasma cyclic AMP response to intravenous glucagon. The glucagon stimulated increase in plasma cyclic AMP has been studied in 17 healthy subjects, in 13 hyperthyroid and in 14 hypothyroid patients. Six hyperthyroid and 2 hypothyroid patients were re-investigated after at least 15 months of treatment. The results show: 1) The glucagon stimulated cyclic AMP response is significantly increased in hyperthyroid patients considered as a group, and is reduced in patients with hypothyroidism. 2) Three hyperthyroid and 4 hypothyroid patients showed a normal response to iv glucagon, indicating that the plasma cyclic AMP response to iv glucagon is not a sensitive test for the evaluation of peripheral thyroid states. This suggests that the effects of thyroid hormones in the liver does not necessarily follow the effects in other tissues. 3) Re-investigation of treated patients showed that the cyclic AMP response can be normalized by treatment, both in hyperthyroidism and hypothyroidism. However, in patients treated for hyperthyroidism a hyper-response to glucagon can continue after blood levels of thyroid hormones are reduced to normal. This suggests an inertia in the loss of the hyper-response to glucagon, once a hyperfunction has been induced. A similar inertia in the loss of glucagon sensitivity in hypothyroidism could explain the large number of normal tests in hypothyroid patients."}
{"id": "PMID:196465", "title": "Hyaline cytoplasmic inclusions in human hepatoma. A case report.", "content": "A case of hepatoma in a 79-year old woman is reported. The patient had an enlarged liver and a pathological liver scintigram. Percutaneous liver biopsies were performed both with Menghini-and fine needles. The most prominent feature was the presence of hyaline cytoplasmic PAS-negative inclusions in liver parenchymal cells. There was no nuclear atypia. Electron microscopy disclosed two types of cytoplasmic changes. One consisted of a lamellar ultrastructure and was interpreted as a hyperplasia of smooth-surfaced endoplasmic reticulum. The other change consisted of smooth globular non-membrane limited regions containing amorphous or finely fibrillar material. This was interpreted as corresponding to the hyaline inclusions visible in the light microscope. The presence of PAS-negative hyaline cytoplasmic inclusions may thus be a sign of hepatoma. This may be of relevance for the diagnostic considerations of material obtained by fine needle biopsy.", "contents": "Hyaline cytoplasmic inclusions in human hepatoma. A case report. A case of hepatoma in a 79-year old woman is reported. The patient had an enlarged liver and a pathological liver scintigram. Percutaneous liver biopsies were performed both with Menghini-and fine needles. The most prominent feature was the presence of hyaline cytoplasmic PAS-negative inclusions in liver parenchymal cells. There was no nuclear atypia. Electron microscopy disclosed two types of cytoplasmic changes. One consisted of a lamellar ultrastructure and was interpreted as a hyperplasia of smooth-surfaced endoplasmic reticulum. The other change consisted of smooth globular non-membrane limited regions containing amorphous or finely fibrillar material. This was interpreted as corresponding to the hyaline inclusions visible in the light microscope. The presence of PAS-negative hyaline cytoplasmic inclusions may thus be a sign of hepatoma. This may be of relevance for the diagnostic considerations of material obtained by fine needle biopsy."}
{"id": "PMID:196463", "title": "Herpesvirus infection of the respiratory tract electronmicroscopic observation of the virus in cells obtained from a sputum cytology.", "content": "A case of herpesvirus infection of the respiratory tract in which the virus was seen ultrastructurally in cells obtained from a routine sputum collected for cytology studies, is presented. The method described would seem feasible for additonal studies at the ultrastructural level of cells obtained during collection of material for routine cytology of the respiratory tract. In the present case the virus particles were easily seen and characterized.", "contents": "Herpesvirus infection of the respiratory tract electronmicroscopic observation of the virus in cells obtained from a sputum cytology. A case of herpesvirus infection of the respiratory tract in which the virus was seen ultrastructurally in cells obtained from a routine sputum collected for cytology studies, is presented. The method described would seem feasible for additonal studies at the ultrastructural level of cells obtained during collection of material for routine cytology of the respiratory tract. In the present case the virus particles were easily seen and characterized."}
{"id": "PMID:196469", "title": "Effect of insulin and adrenaline on cyclic AMP in the diaphragm of normal and diabetic rats.", "content": "The effects of insulin and adrenaline on cyclic AMP (cAMP) levels in diaphragms of normal, streptozotocin-diabetic and insulin-treated diabetic rats were studied. Adrenaline caused a biphasic rise in cAMP with peak values of cAMP within the first few minutes. Diaphragms of diabetic rats showed an increased responsiveness to adrenaline. Injection of insulin to diabetic rats normalized the rise in cAMP after addition of adrenaline. There was no difference in basal levels of cAMP between diaphragms of normal, diabetic or insulin-treated diabetic rats. Insulin in vitro did not affect basal cAMP-levels or the release of cAMP from the tissue but significantly decreased adrenaline-induced peak levels of cAMP. This effect of insulin was abolished by theophylline. The results of the present study suggest that experimental diabetes is associated with changes of the adenylate cyclase and/or phosphodiesterase enzyme activities in skeletal muscle resulting in an increased responsiveness to adrenaline. Since insulin in vitro depressed the adrenaline-induced elevation of cAMP the increased responsiveness in diaphragms of diabetic rats might be attributed to the specific lack of insulin.", "contents": "Effect of insulin and adrenaline on cyclic AMP in the diaphragm of normal and diabetic rats. The effects of insulin and adrenaline on cyclic AMP (cAMP) levels in diaphragms of normal, streptozotocin-diabetic and insulin-treated diabetic rats were studied. Adrenaline caused a biphasic rise in cAMP with peak values of cAMP within the first few minutes. Diaphragms of diabetic rats showed an increased responsiveness to adrenaline. Injection of insulin to diabetic rats normalized the rise in cAMP after addition of adrenaline. There was no difference in basal levels of cAMP between diaphragms of normal, diabetic or insulin-treated diabetic rats. Insulin in vitro did not affect basal cAMP-levels or the release of cAMP from the tissue but significantly decreased adrenaline-induced peak levels of cAMP. This effect of insulin was abolished by theophylline. The results of the present study suggest that experimental diabetes is associated with changes of the adenylate cyclase and/or phosphodiesterase enzyme activities in skeletal muscle resulting in an increased responsiveness to adrenaline. Since insulin in vitro depressed the adrenaline-induced elevation of cAMP the increased responsiveness in diaphragms of diabetic rats might be attributed to the specific lack of insulin."}
{"id": "PMID:196470", "title": "In vitro temporal cAMP and cortisol responses to ACTH by the normal human adrenal gland.", "content": "The in vitro temporal cAMP and cortisol responses of normal human adrenocortical tissue to ACTH were evaluated. ACTH stimulated rapid increased in cAMP levels and cortisol output, however, significantly increased cAMP levels preceded output only at the higher ACTH doses studied. Cortisol output plateaued with ACTH (10--100 MIU/ml) while cAMP levels continued to increase. The findings indicate that the unitary role of cAMP as the second messenger of ACTH action in the human adrenal cannot be assumed from data derived from lower forms and that the mechanism of action of ACTH in the human may be modulated by additional factors.", "contents": "In vitro temporal cAMP and cortisol responses to ACTH by the normal human adrenal gland. The in vitro temporal cAMP and cortisol responses of normal human adrenocortical tissue to ACTH were evaluated. ACTH stimulated rapid increased in cAMP levels and cortisol output, however, significantly increased cAMP levels preceded output only at the higher ACTH doses studied. Cortisol output plateaued with ACTH (10--100 MIU/ml) while cAMP levels continued to increase. The findings indicate that the unitary role of cAMP as the second messenger of ACTH action in the human adrenal cannot be assumed from data derived from lower forms and that the mechanism of action of ACTH in the human may be modulated by additional factors."}
{"id": "PMID:196467", "title": "Effect of potassium on human and rat liver glucose-6-phosphatase.", "content": "Potassium chloride concentrations of 100-150 mM were shown to inhibit (20-40%) human and rat liver microsomal glucose-6-phosphatase when the substrate was reduced to physiological concentration. When the enzyme was solubilized by treatment of microsomes with A12O3 the inhibition could be observed at greater substrate concentrations. Since potassium deprivation is associated with hyperglycemia in both animals and man, these observations may have physiological significance.", "contents": "Effect of potassium on human and rat liver glucose-6-phosphatase. Potassium chloride concentrations of 100-150 mM were shown to inhibit (20-40%) human and rat liver microsomal glucose-6-phosphatase when the substrate was reduced to physiological concentration. When the enzyme was solubilized by treatment of microsomes with A12O3 the inhibition could be observed at greater substrate concentrations. Since potassium deprivation is associated with hyperglycemia in both animals and man, these observations may have physiological significance."}
{"id": "PMID:196471", "title": "Responses of serum gonadotrophins to LH-releasing hormone and oestrogens in Japanese women with polycystic ovaries.", "content": "In order to define the abnormality in gonadotrophin secretion in Japanese women with polycystic ovaries (PCO) who rarely show virilization and markedly enlarged ovaries, basal levels of LH and FSH, and responses of serum gonadotrophins to LH-releasing hormone (LH-RH) or oestrogens were determined by radioimmunoassay. Eleven patients with PCO diagnosed by laparotomy or laparoscopy and 30 normal women in the follicular phase were studied. The mean (+/- SD) basal level of LH was significantly higher in patients with PCO than in normal controls (PCO 28.6 +/- 2.4 vs. normal 10.9 +/- 3.0 mIU/ml), while the mean FSH level in PCO patients was not significantly different from that in the normal controls (9.7 +/- 0.7 vs. 11.4 +/- 2.6 mIU/ml). The mean LH/FSH ratio in PCO patients was significantly higher than that in normal controls (3.2 +/- 0.9 vs. 1.0 +/- 0.3). Exaggerated response of LH to LH-RH was observed in PCO patients, while the FSH response was comparable with the normal controls. Ten out of 11 patients with PCO showed LH release exceeding the basal level after bolus iv injection of 20 mg conjugated oestrogens (Premarin), and virtually the same mean net increase in LH from the basal level was obtained in both PCO patients and normal controls. Since the abnormalities in gonadotrophin secretion in Japanese women with PCO are not different from those reported in patients with PCO in Europe and USA, it seems likely that lower incidence of markedly enlarged ovaries and virilization in Japanese patients may be caused by the difference in ovarian response to gonadotrophin.", "contents": "Responses of serum gonadotrophins to LH-releasing hormone and oestrogens in Japanese women with polycystic ovaries. In order to define the abnormality in gonadotrophin secretion in Japanese women with polycystic ovaries (PCO) who rarely show virilization and markedly enlarged ovaries, basal levels of LH and FSH, and responses of serum gonadotrophins to LH-releasing hormone (LH-RH) or oestrogens were determined by radioimmunoassay. Eleven patients with PCO diagnosed by laparotomy or laparoscopy and 30 normal women in the follicular phase were studied. The mean (+/- SD) basal level of LH was significantly higher in patients with PCO than in normal controls (PCO 28.6 +/- 2.4 vs. normal 10.9 +/- 3.0 mIU/ml), while the mean FSH level in PCO patients was not significantly different from that in the normal controls (9.7 +/- 0.7 vs. 11.4 +/- 2.6 mIU/ml). The mean LH/FSH ratio in PCO patients was significantly higher than that in normal controls (3.2 +/- 0.9 vs. 1.0 +/- 0.3). Exaggerated response of LH to LH-RH was observed in PCO patients, while the FSH response was comparable with the normal controls. Ten out of 11 patients with PCO showed LH release exceeding the basal level after bolus iv injection of 20 mg conjugated oestrogens (Premarin), and virtually the same mean net increase in LH from the basal level was obtained in both PCO patients and normal controls. Since the abnormalities in gonadotrophin secretion in Japanese women with PCO are not different from those reported in patients with PCO in Europe and USA, it seems likely that lower incidence of markedly enlarged ovaries and virilization in Japanese patients may be caused by the difference in ovarian response to gonadotrophin."}
{"id": "PMID:196472", "title": "Ovarian HCG-binding capacity during the oestrous cycle of the rat.", "content": "Binding in 125I-labelled HCG to rat ovary varies during the oestrus cycle. The highest amount of binding was found in dioestrous-II rats (7.33 X 10(-15) mol of HCG per mg wet weight), while the lowest binding was observed in oestrous rats (1.67 X 10(-15) mol of HCG per mg wet weight) of circulation LH. It is concluded that the low binding capacity of the rat ovary in the oestrous stage is due to masking of the specific receptors by the excessively high LH hormone secretion in pro-oestrus.", "contents": "Ovarian HCG-binding capacity during the oestrous cycle of the rat. Binding in 125I-labelled HCG to rat ovary varies during the oestrus cycle. The highest amount of binding was found in dioestrous-II rats (7.33 X 10(-15) mol of HCG per mg wet weight), while the lowest binding was observed in oestrous rats (1.67 X 10(-15) mol of HCG per mg wet weight) of circulation LH. It is concluded that the low binding capacity of the rat ovary in the oestrous stage is due to masking of the specific receptors by the excessively high LH hormone secretion in pro-oestrus."}
{"id": "PMID:196466", "title": "Studies of hormonal regulation of metabolism using isolated hepatocytes.", "content": "A number of enzymatic methods have been developed to prepare hepatocytes using collagenase and hyaluronidase. However, best cell preparations are obtained by using only low concentrations of collagenase and exposing the liver to the enzyme for a very short period of time. These isolated cells with intact cell membranes and large numbers of microvilli on the cell surface respond to hormones at physiological concentrations suggesting that these microvilli contain hormone receptors. In addition, high glycogen content is essential to maintain the in vivo metabolic characteristics of the hepatocytes suggesting that intracellular glycogen plays an important role in the hormonal regulation of metabolism in hepatocytes. Studies with glucagon and insulin on carbohydrate metabolism show that the molar ratios of these hormones control gluconeogenesis and glycogenolysis. Furthermore, in vitro addition of insulin stimulates glycogen synthesis and activates glycogen synthase. Insulin also stimulates protein synthesis in cells containing high glycogen and maintains more normal parallel strands of polyribosomes. Studies with isolated hepatocytes from diabetic, hypophysectomized and adrenalectomized animals show a reduced glucagon response to glycogenolysis. This lack of glucagon response was not due to reduction in glycogen levels. Other hormones such as somatostatin and parathyroid also give rise to alterations in carbohydrate metabolism in isolated hepatocytes.", "contents": "Studies of hormonal regulation of metabolism using isolated hepatocytes. A number of enzymatic methods have been developed to prepare hepatocytes using collagenase and hyaluronidase. However, best cell preparations are obtained by using only low concentrations of collagenase and exposing the liver to the enzyme for a very short period of time. These isolated cells with intact cell membranes and large numbers of microvilli on the cell surface respond to hormones at physiological concentrations suggesting that these microvilli contain hormone receptors. In addition, high glycogen content is essential to maintain the in vivo metabolic characteristics of the hepatocytes suggesting that intracellular glycogen plays an important role in the hormonal regulation of metabolism in hepatocytes. Studies with glucagon and insulin on carbohydrate metabolism show that the molar ratios of these hormones control gluconeogenesis and glycogenolysis. Furthermore, in vitro addition of insulin stimulates glycogen synthesis and activates glycogen synthase. Insulin also stimulates protein synthesis in cells containing high glycogen and maintains more normal parallel strands of polyribosomes. Studies with isolated hepatocytes from diabetic, hypophysectomized and adrenalectomized animals show a reduced glucagon response to glycogenolysis. This lack of glucagon response was not due to reduction in glycogen levels. Other hormones such as somatostatin and parathyroid also give rise to alterations in carbohydrate metabolism in isolated hepatocytes."}
{"id": "PMID:196475", "title": "Effect of corticotropin, steroidogenic inhibitors and hypophysectomy on the nuclear volumes of fasciculata cells in the rat adrenal cortex.", "content": "The purpose of this investigation was to measure quantitatively nuclear volumes in outer fasciculata cells in adrenal glands of rats subjected to chronic stimulation of steroidogenesis by ACTH, or to chronic inhibition of functional activity by hypophysectomy or by injection of the steroidogenic inhibitos, U-8113 (p-aminophenyl butanone) and SU-4885 (metopirone). Nuclear volumes, after a recovery period from those effects, were also measured. Chronic daily administrations of ACTH for 7, 14, and 30 days led to a progressive, statistically significant increase in nuclear volumes of fasciculata cells. These changes were found to have been reversed 14 days after discontinuation of hormone treatment. Hypophysectomy resulted in a significant decrease in nuclear volumes. The steroidogenic inhibitors SU-4885 and U-8113 had a biphasic effect on the nuclear volumes with an early decrease and subsequent increase to normal values. Since a decrease in nuclear volumes in the adrenal glands of inhibitor-treated subjects occurred in the presence of cellular hypertrophy and a significant increase in adrenal weights, it is concluded that changes in nuclear volumes can be positively correlated with the secretory activity of the cell rather than with the sizes of cells or glands.", "contents": "Effect of corticotropin, steroidogenic inhibitors and hypophysectomy on the nuclear volumes of fasciculata cells in the rat adrenal cortex. The purpose of this investigation was to measure quantitatively nuclear volumes in outer fasciculata cells in adrenal glands of rats subjected to chronic stimulation of steroidogenesis by ACTH, or to chronic inhibition of functional activity by hypophysectomy or by injection of the steroidogenic inhibitos, U-8113 (p-aminophenyl butanone) and SU-4885 (metopirone). Nuclear volumes, after a recovery period from those effects, were also measured. Chronic daily administrations of ACTH for 7, 14, and 30 days led to a progressive, statistically significant increase in nuclear volumes of fasciculata cells. These changes were found to have been reversed 14 days after discontinuation of hormone treatment. Hypophysectomy resulted in a significant decrease in nuclear volumes. The steroidogenic inhibitors SU-4885 and U-8113 had a biphasic effect on the nuclear volumes with an early decrease and subsequent increase to normal values. Since a decrease in nuclear volumes in the adrenal glands of inhibitor-treated subjects occurred in the presence of cellular hypertrophy and a significant increase in adrenal weights, it is concluded that changes in nuclear volumes can be positively correlated with the secretory activity of the cell rather than with the sizes of cells or glands."}
{"id": "PMID:196479", "title": "Indirect immunofluorescence detection of human IgM and IgG antibodies against herpes simplex virus type 1 induced cell surface antigens.", "content": "An indirect immunofluorescence method, based on the use of infected Hela cell coverslip cultures was developed to demonstrate human IgM and IgG class antibodies against herpes simplex virus (HSV) type 1 induced cell surface antigens. A total of 35 specimens from 20 patients have been tested; including patients with a clinical diagnosis of HSV type 1 or type 2 primary infection, patients with recurrent HSV infections, patients without any HSV infections, and patients with varicella-zoster virus (VZV) infections. In each patient with a primary HSV infection both IgM and IgG antibody response was observed, while the patients with recurrent HSV infections showed only IgG antibodies. The direct serological typing of HSV infections was not possible because of cross-reacting antibodies both in the IgG and IgM test. No cross-reactivity was found in this test with HSV and VZV antibodies. The HSV fluorescent IgG and IgM antibody titers were found to parallel the highly sensitive HSV radioimmunoassay antibody titers very closely though at a markedly lower level.", "contents": "Indirect immunofluorescence detection of human IgM and IgG antibodies against herpes simplex virus type 1 induced cell surface antigens. An indirect immunofluorescence method, based on the use of infected Hela cell coverslip cultures was developed to demonstrate human IgM and IgG class antibodies against herpes simplex virus (HSV) type 1 induced cell surface antigens. A total of 35 specimens from 20 patients have been tested; including patients with a clinical diagnosis of HSV type 1 or type 2 primary infection, patients with recurrent HSV infections, patients without any HSV infections, and patients with varicella-zoster virus (VZV) infections. In each patient with a primary HSV infection both IgM and IgG antibody response was observed, while the patients with recurrent HSV infections showed only IgG antibodies. The direct serological typing of HSV infections was not possible because of cross-reacting antibodies both in the IgG and IgM test. No cross-reactivity was found in this test with HSV and VZV antibodies. The HSV fluorescent IgG and IgM antibody titers were found to parallel the highly sensitive HSV radioimmunoassay antibody titers very closely though at a markedly lower level."}
{"id": "PMID:196480", "title": "T-typing of group A streptococci from clinical specimens: restriction of the number if implied M types in each T-pattern by tests for opacity factor and nicotinamide adenine dinucleotide glycohydrolase.", "content": "117 group A streptococci, consecutively isolated from routine throat swab cultures, were T-typed and further characterized according to their enzyme reactions. The results of typing with two different commercial kits of anti-T sera showed good agreement. 89 per cent of the strains were typable by either of these kits. 68 per cent of the strains were OF-positive and 95 per cent NADse-positive. With T-typing alone, 22 per cent of the strains showed agglutination patterns implying only one M type each. When considered together, the T-typing and enzyme reactions made it possible to implicate one M type only for each of 45 per cent of the strains. In a further 34 per cent of the strains, the possible M type of each strain was restricted to four types. However, these findings were hampered by the fact that the T patterns of a number of more seldom met group A streptococci have not been investigated adequately.", "contents": "T-typing of group A streptococci from clinical specimens: restriction of the number if implied M types in each T-pattern by tests for opacity factor and nicotinamide adenine dinucleotide glycohydrolase. 117 group A streptococci, consecutively isolated from routine throat swab cultures, were T-typed and further characterized according to their enzyme reactions. The results of typing with two different commercial kits of anti-T sera showed good agreement. 89 per cent of the strains were typable by either of these kits. 68 per cent of the strains were OF-positive and 95 per cent NADse-positive. With T-typing alone, 22 per cent of the strains showed agglutination patterns implying only one M type each. When considered together, the T-typing and enzyme reactions made it possible to implicate one M type only for each of 45 per cent of the strains. In a further 34 per cent of the strains, the possible M type of each strain was restricted to four types. However, these findings were hampered by the fact that the T patterns of a number of more seldom met group A streptococci have not been investigated adequately."}
{"id": "PMID:196500", "title": "Clinical electromyography: definition, application, and innovation.", "content": "Clinical EMG techniques, useful in the study of patients with neuromuscular disease, are defined. These include measurement of motor and sensory nerve conduction velocities; analysis of the size, shape, and latency of response of muscle and nerve action potentials after nerve stimulation; estimates of nerve excitability; study of the response to repetitive nerve stimulation as a measure of neuromuscular transmission; and observation of the electrical activity of muscle with needle recording electrodes (monopolar, bipolar, and multielectrodes). From a consideration of the application, limitations, and value of these various techniques, it can be concluded logically that to assure the highest probability of reliable information in regard to an individual patient, the choice of technique(s) and the part(s) to be studied should be intimately tied to a clinical analysis of that patient's problem. EMG as a fishing expedition is rarely fruitful; EMG as an exercise in clinical physiology is often exciting.", "contents": "Clinical electromyography: definition, application, and innovation. Clinical EMG techniques, useful in the study of patients with neuromuscular disease, are defined. These include measurement of motor and sensory nerve conduction velocities; analysis of the size, shape, and latency of response of muscle and nerve action potentials after nerve stimulation; estimates of nerve excitability; study of the response to repetitive nerve stimulation as a measure of neuromuscular transmission; and observation of the electrical activity of muscle with needle recording electrodes (monopolar, bipolar, and multielectrodes). From a consideration of the application, limitations, and value of these various techniques, it can be concluded logically that to assure the highest probability of reliable information in regard to an individual patient, the choice of technique(s) and the part(s) to be studied should be intimately tied to a clinical analysis of that patient's problem. EMG as a fishing expedition is rarely fruitful; EMG as an exercise in clinical physiology is often exciting."}
{"id": "PMID:196503", "title": "Primary hyperparathyroidism presenting as anticonvulsant-induced osteomalacia.", "content": "A patient presented with the classic features of anticonvulsant-induced osteomalacia. Following discontinuance of diphenylhydantoin therapy and repletion with physiologic quantities of vitamin D, hypercalcemia and persistent biochemical hyperparathyroidism developed, and a parathyroid adenoma was removed. A history of nephrolithiasis and hypercalcemia preceding the institution of drug therapy allowed this patient's underlying parathyroid disease to be defined as primary hyperparathyroidism, which had been obscured by anticonvulsant therapy.", "contents": "Primary hyperparathyroidism presenting as anticonvulsant-induced osteomalacia. A patient presented with the classic features of anticonvulsant-induced osteomalacia. Following discontinuance of diphenylhydantoin therapy and repletion with physiologic quantities of vitamin D, hypercalcemia and persistent biochemical hyperparathyroidism developed, and a parathyroid adenoma was removed. A history of nephrolithiasis and hypercalcemia preceding the institution of drug therapy allowed this patient's underlying parathyroid disease to be defined as primary hyperparathyroidism, which had been obscured by anticonvulsant therapy."}
{"id": "PMID:196504", "title": "Structural changes in the freeze-fractured sarcolemma of ischemic myocardium.", "content": "Ultrastructural alterations in the sarcolemma of ischemic myocardium were studied with the freeze-fracture technique. In normal myocardial sarcolemma, the P fracture face contained many intramembranous particles which were randomly distributed, while the E fracture face had few intramembranous particles; no structural abnormalities were seen within the lipid bilayer on either face. Myocardium ischemic for 45 minutes displayed no, or only slight, aggregation of intramembranous particles, but upon reperfusion for 5 to 20 minutes, the particles became significantly aggregated in the P face. Scattered nicks within the lipid bilayer were observed on both fracture faces. Intramembranous particles were similarly aggregated in myocardium ischemic for 2 hours; however, the number of nicks were greatly increased on the P and E fracture faces. These structural alterations, which were undetected in thin sections, are likely to be associated with altered function in the sarcolemma of ischemic myocardium.", "contents": "Structural changes in the freeze-fractured sarcolemma of ischemic myocardium. Ultrastructural alterations in the sarcolemma of ischemic myocardium were studied with the freeze-fracture technique. In normal myocardial sarcolemma, the P fracture face contained many intramembranous particles which were randomly distributed, while the E fracture face had few intramembranous particles; no structural abnormalities were seen within the lipid bilayer on either face. Myocardium ischemic for 45 minutes displayed no, or only slight, aggregation of intramembranous particles, but upon reperfusion for 5 to 20 minutes, the particles became significantly aggregated in the P face. Scattered nicks within the lipid bilayer were observed on both fracture faces. Intramembranous particles were similarly aggregated in myocardium ischemic for 2 hours; however, the number of nicks were greatly increased on the P and E fracture faces. These structural alterations, which were undetected in thin sections, are likely to be associated with altered function in the sarcolemma of ischemic myocardium."}
{"id": "PMID:196505", "title": "Lipid accumulation of hypoxic tissue culture cells.", "content": "Lipid droplets have long been recognized by light microscopy to accumulate in hypoxic cells both in vivo and in vitro. In the present tissue culture experiments, correlative electron microscopic observations and lipid analyses were performed to determine the nature and significance of lipid accumulation in hypoxia. Strain L mouse fibroblasts were grown in suspension culture, both aerobically and under severe oxygen restriction obtained by gassing cultures daily with an 8% CO(2)-92% nitrogen mixture. After 48 hours, hypoxic cells showed an increase in total lipid/protein ratio of 42% over control cells. Most of this increase was accounted for by an elevation in the level of cellular triglyceride from 12.3 +/- 0.9 mug/mg cell protein in aerobic cultures to 41.9 +/- 0.7 in the hypoxic cultures, an increase of 240%. Levels of cellular free fatty acids (FFA) were 96% higher in the hypoxic cultures. No significant changes in the levels of cellular phospholipid or cholesterol were noted. Electron microscopic examination revealed the accumulation of homogeneous cytoplasmic droplets. The hypoxic changes were reversible upon transferring the cultures to aerobic atmospheres with disappearance of the lipid. These experiments indicate that hypoxic injury initially results in triglyceride and FFA accumulation from an inability to oxidize fatty acids taken up from the media and not from autophagic processes, as described in other types of cell injury associated with the sequestration of membranous residues and intracellular cholesterol and phospholipid accumulation.", "contents": "Lipid accumulation of hypoxic tissue culture cells. Lipid droplets have long been recognized by light microscopy to accumulate in hypoxic cells both in vivo and in vitro. In the present tissue culture experiments, correlative electron microscopic observations and lipid analyses were performed to determine the nature and significance of lipid accumulation in hypoxia. Strain L mouse fibroblasts were grown in suspension culture, both aerobically and under severe oxygen restriction obtained by gassing cultures daily with an 8% CO(2)-92% nitrogen mixture. After 48 hours, hypoxic cells showed an increase in total lipid/protein ratio of 42% over control cells. Most of this increase was accounted for by an elevation in the level of cellular triglyceride from 12.3 +/- 0.9 mug/mg cell protein in aerobic cultures to 41.9 +/- 0.7 in the hypoxic cultures, an increase of 240%. Levels of cellular free fatty acids (FFA) were 96% higher in the hypoxic cultures. No significant changes in the levels of cellular phospholipid or cholesterol were noted. Electron microscopic examination revealed the accumulation of homogeneous cytoplasmic droplets. The hypoxic changes were reversible upon transferring the cultures to aerobic atmospheres with disappearance of the lipid. These experiments indicate that hypoxic injury initially results in triglyceride and FFA accumulation from an inability to oxidize fatty acids taken up from the media and not from autophagic processes, as described in other types of cell injury associated with the sequestration of membranous residues and intracellular cholesterol and phospholipid accumulation."}
{"id": "PMID:196506", "title": "Macrophage migratory dysfunction in cancer. A mechanism for subversion of surveillance.", "content": "There is considerable evidence to suggest that macrophages participate in host resistance to the development and spread of cancer. We have, therefore, studied monocytemacrophage function in humans and animals with neoplasms. Approximately 60% of patients with various types of cancer were found to have abnormal monocyte chemotactic responsiveness in vitro, and abnormal chemotaxis was an indicator of poor prognosis in patients with melanoma. By studying patients before and after surgery, it was found that abnormal chemotactic responses normalized within weeks after removal of malignant tumors, indicating that a neoplasm itself might affect the host's monocyte chemotactic responsiveness. Subsequent studies using transplantable neoplasms in mice substantiated this hypothesis in that macrophage accumulation in vivo as well as macrophage chemotactic responsiveness in vitro was depressed in animals during the early phases of tumor growth. This depression of macrophage function could be attributed to a low-molecular-weight factor contained in murine neoplasms, which when given to normal mice was extremely potent in depressing peritoneal macrophage accumulation and chemotaxis but, paradoxically, enhanced phagocytosis. The serum of tumor-bearing mice also contained potent inhibitory activity for macrophage accumulation. In contrast to the effects on macrophages, granulocyte accumulation in vivo and chemotaxis in vitro was not depressed by the presence of a neoplasm or the administration of the factor from neoplasms. By releasing factors which depress macrophage migratory function, neoplasms may protect themselves from immunologically mediated host destruction during the early phases of tumor growth.", "contents": "Macrophage migratory dysfunction in cancer. A mechanism for subversion of surveillance. There is considerable evidence to suggest that macrophages participate in host resistance to the development and spread of cancer. We have, therefore, studied monocytemacrophage function in humans and animals with neoplasms. Approximately 60% of patients with various types of cancer were found to have abnormal monocyte chemotactic responsiveness in vitro, and abnormal chemotaxis was an indicator of poor prognosis in patients with melanoma. By studying patients before and after surgery, it was found that abnormal chemotactic responses normalized within weeks after removal of malignant tumors, indicating that a neoplasm itself might affect the host's monocyte chemotactic responsiveness. Subsequent studies using transplantable neoplasms in mice substantiated this hypothesis in that macrophage accumulation in vivo as well as macrophage chemotactic responsiveness in vitro was depressed in animals during the early phases of tumor growth. This depression of macrophage function could be attributed to a low-molecular-weight factor contained in murine neoplasms, which when given to normal mice was extremely potent in depressing peritoneal macrophage accumulation and chemotaxis but, paradoxically, enhanced phagocytosis. The serum of tumor-bearing mice also contained potent inhibitory activity for macrophage accumulation. In contrast to the effects on macrophages, granulocyte accumulation in vivo and chemotaxis in vitro was not depressed by the presence of a neoplasm or the administration of the factor from neoplasms. By releasing factors which depress macrophage migratory function, neoplasms may protect themselves from immunologically mediated host destruction during the early phases of tumor growth."}
{"id": "PMID:196507", "title": "Couples group therapy as an adjunct to lithium maintenance of the manic patient.", "content": "Use of couples therapy groups in conjunction with lithium in the long-term management of married manic-depressive patients is described. Among bipolar patients on lithium, those in couples group therapy had more benign posthospital course than those given minimal support beyond medication. The structure and benefits of the couples group are discussed.", "contents": "Couples group therapy as an adjunct to lithium maintenance of the manic patient. Use of couples therapy groups in conjunction with lithium in the long-term management of married manic-depressive patients is described. Among bipolar patients on lithium, those in couples group therapy had more benign posthospital course than those given minimal support beyond medication. The structure and benefits of the couples group are discussed."}
{"id": "PMID:196508", "title": "Evidence for glomerular actions of ADH and dibutyryl cyclic AMP in the rat.", "content": "Experiments were performed on 54 chronically water diuretic Munich-Wistar rats to investigate the effects of various antidiuretic peptides on the determinants of glomerular ultrafiltration. Transition from water diuresis to antidiuresis, induced either by intravenous infusion of 1) exogenous peptides (Pitressin, synthetic arginine vasopressin, or synthetic [1-deamino,4-valine]-8-D-arginine vasopressin) or 2) dibutyryl cyclic AMP, or by stimulation of endogenous ADH release by acute, mild arterial hemorrhage, was associated with near-constant or decreased values for single nephron (SN) and total kidney GFR. Nevertheless, the glomerular transcapillary hydraulic pressure difference (deltaP) uniformly increased with antidiuresis, due to consistent reductions in Bowman's space hydraulic pressure rather than to increases in glomerular capillary hydraulic pressure, the former a consequence of the fall in urine flow rate. In all antidiuretic states, the rats were uniformly observed to be at filtration pressure disequilibrium, permitting calculation of unique values of the glomerular ultrafiltration coefficient (Kf). These values of Kf in antidiuresis were invariably lower than the values obtained during water diuresis. Whether these effects of ADH and DBcAMP on deltaP and Kf represent physiological influences in the control of GFR remains uncertain; their offsetting effects in the present studies usually failed to alter GFR appreciably.", "contents": "Evidence for glomerular actions of ADH and dibutyryl cyclic AMP in the rat. Experiments were performed on 54 chronically water diuretic Munich-Wistar rats to investigate the effects of various antidiuretic peptides on the determinants of glomerular ultrafiltration. Transition from water diuresis to antidiuresis, induced either by intravenous infusion of 1) exogenous peptides (Pitressin, synthetic arginine vasopressin, or synthetic [1-deamino,4-valine]-8-D-arginine vasopressin) or 2) dibutyryl cyclic AMP, or by stimulation of endogenous ADH release by acute, mild arterial hemorrhage, was associated with near-constant or decreased values for single nephron (SN) and total kidney GFR. Nevertheless, the glomerular transcapillary hydraulic pressure difference (deltaP) uniformly increased with antidiuresis, due to consistent reductions in Bowman's space hydraulic pressure rather than to increases in glomerular capillary hydraulic pressure, the former a consequence of the fall in urine flow rate. In all antidiuretic states, the rats were uniformly observed to be at filtration pressure disequilibrium, permitting calculation of unique values of the glomerular ultrafiltration coefficient (Kf). These values of Kf in antidiuresis were invariably lower than the values obtained during water diuresis. Whether these effects of ADH and DBcAMP on deltaP and Kf represent physiological influences in the control of GFR remains uncertain; their offsetting effects in the present studies usually failed to alter GFR appreciably."}
{"id": "PMID:196509", "title": "Renin release and pressor response to renal arterial hypotension: effect of dietary sodium.", "content": "Changes in plasma renin activity (PRA) and mean arterial pressure (MAP) produced by renal arterial hypotension were studied in conscious, adrenalectomized dogs maintained on low-, normal-, or high-Na diet during constant steroid replacement therapy. In animals maintained on a low-Na diet, reduction of renal perfusion pressure to 50 mmHg for 45 min increased MAP 40 +/- 3 (SE) mmHg, while PRA rose rapidly by 36.5 +/- 6 ng ml-1 h-1. Similar renal hypotension in dogs maintained on a normal-Na diet increased MAP only 21 +/- 3 mmHg while PRA rose 5.5 +/- 0.9 ng ml-1 h-1; dogs on high-Na intake had a 6 +/- 1 mmHg pressure rise without a significant change in PRA. The rise in MAP correlated well with the log deltaPRA. Calculated open-loop gain was -1.2, -0.7, and -0.1 in dogs on low-, normal-, and high-Na diets, respectively. Nonpeptide angiotensin I converting enzyme inhibitor (CEI) reversed the elevated MAP observed during reduction of renal perfusion pressure in dogs on low- and normal-Na diets, but had little effect in dogs on high-Na intake. These observations suggest that the renin-angiotensin system becomes quantitatively more important in the regulation of blood pressure as Na intake is reduced.", "contents": "Renin release and pressor response to renal arterial hypotension: effect of dietary sodium. Changes in plasma renin activity (PRA) and mean arterial pressure (MAP) produced by renal arterial hypotension were studied in conscious, adrenalectomized dogs maintained on low-, normal-, or high-Na diet during constant steroid replacement therapy. In animals maintained on a low-Na diet, reduction of renal perfusion pressure to 50 mmHg for 45 min increased MAP 40 +/- 3 (SE) mmHg, while PRA rose rapidly by 36.5 +/- 6 ng ml-1 h-1. Similar renal hypotension in dogs maintained on a normal-Na diet increased MAP only 21 +/- 3 mmHg while PRA rose 5.5 +/- 0.9 ng ml-1 h-1; dogs on high-Na intake had a 6 +/- 1 mmHg pressure rise without a significant change in PRA. The rise in MAP correlated well with the log deltaPRA. Calculated open-loop gain was -1.2, -0.7, and -0.1 in dogs on low-, normal-, and high-Na diets, respectively. Nonpeptide angiotensin I converting enzyme inhibitor (CEI) reversed the elevated MAP observed during reduction of renal perfusion pressure in dogs on low- and normal-Na diets, but had little effect in dogs on high-Na intake. These observations suggest that the renin-angiotensin system becomes quantitatively more important in the regulation of blood pressure as Na intake is reduced."}
{"id": "PMID:196511", "title": "Involvement of cAMP-dependent protein kinase in the regulation of heart contractile force.", "content": "The effects of perfusate epinephrine, 1-methyl-3-isobutylxanthine, calcium, and filling pressure were investigated in the perfused working rat heart. Epinephrine produced a rapid increase in cAMP, in the protein kinase activity ratio, and in active phosphorylase. These effects preceded the increase in contractile force produced by the hormone. There was good correlation between protein kinase activation and the increase in force. Epinephrine and the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine were synergistic in their stimulatory effects on cAMP, protein kinase activity, active phosphorylase, and contractile force. When an increase in the force of contraction was produced either by increasing the filling pressure of the heart or by increasing the perfusate Ca2+ concentration, there was no change in either cAMP levels or protein kinase activity. These data suggest that the effect of beta-adrenergic catecholamines on contractile force is due, at least in part, to cAMP-dependent protein kinase activation. The increase in contractile force produced either by increasing the filling pressure (Frank-Starling phenomenon) or by increasing the perfusate Ca2+ concentration is apparently not mediated by cAMP or the protein kinase.", "contents": "Involvement of cAMP-dependent protein kinase in the regulation of heart contractile force. The effects of perfusate epinephrine, 1-methyl-3-isobutylxanthine, calcium, and filling pressure were investigated in the perfused working rat heart. Epinephrine produced a rapid increase in cAMP, in the protein kinase activity ratio, and in active phosphorylase. These effects preceded the increase in contractile force produced by the hormone. There was good correlation between protein kinase activation and the increase in force. Epinephrine and the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine were synergistic in their stimulatory effects on cAMP, protein kinase activity, active phosphorylase, and contractile force. When an increase in the force of contraction was produced either by increasing the filling pressure of the heart or by increasing the perfusate Ca2+ concentration, there was no change in either cAMP levels or protein kinase activity. These data suggest that the effect of beta-adrenergic catecholamines on contractile force is due, at least in part, to cAMP-dependent protein kinase activation. The increase in contractile force produced either by increasing the filling pressure (Frank-Starling phenomenon) or by increasing the perfusate Ca2+ concentration is apparently not mediated by cAMP or the protein kinase."}
{"id": "PMID:196513", "title": "The pseudocapsule of pleomorphic adenomas (benign mixed tumors): the argument against enucleation.", "content": "The \"well encapsulated\" pleomorphic adenoma has at best a pseudocapsule which allows for bits of satellite tumor to be left behind at \"\"enucleation\" surgery as well as for easy \"spillage\" of tumor by the overconfident surgeon. Recurrent pleomorphic adenomas then become difficult tumors to eradicate and place vital structures, such as the facial nerve, in jeopardy.", "contents": "The pseudocapsule of pleomorphic adenomas (benign mixed tumors): the argument against enucleation. The \"well encapsulated\" pleomorphic adenoma has at best a pseudocapsule which allows for bits of satellite tumor to be left behind at \"\"enucleation\" surgery as well as for easy \"spillage\" of tumor by the overconfident surgeon. Recurrent pleomorphic adenomas then become difficult tumors to eradicate and place vital structures, such as the facial nerve, in jeopardy."}
{"id": "PMID:196517", "title": "Multivariate analysis of visual evoked response.", "content": "The visual potentials evoked by flash are analyzed in healthy subjects in cases of retinal detachment, of optic nerve lesions, and of amblyopia by means of different statistical methods: 1. Analysis of the various features of the response, evaluated separately 2. Analysis of the interdependence between the measures of the various features The first method supplies information on the differences in 'size' of the curves in the various samples, the second method reveals differences of 'shape'. The second method has proved to be able to distinguish both normal conditions from pathologic impairment of optic structures and the different sites of the lesions.", "contents": "Multivariate analysis of visual evoked response. The visual potentials evoked by flash are analyzed in healthy subjects in cases of retinal detachment, of optic nerve lesions, and of amblyopia by means of different statistical methods: 1. Analysis of the various features of the response, evaluated separately 2. Analysis of the interdependence between the measures of the various features The first method supplies information on the differences in 'size' of the curves in the various samples, the second method reveals differences of 'shape'. The second method has proved to be able to distinguish both normal conditions from pathologic impairment of optic structures and the different sites of the lesions."}
{"id": "PMID:196518", "title": "[The hypnotic effect of fentanyl and sulfentanil. An electro-encephalographic comparison (author's transl)].", "content": "1. Electroencephalographic activity was registered in healthy subjects before, during and 90 minutes after intravenous injections of sufentanil and fentanyl. 2. With a dosage of ratio of 1:10, i.e., 0.025 mg/70 kg body weight sufentanil: 0.25 mg/70 kg body weight fentanyl as well as 0.015 mg/70 kg body weight sufentanil: 0.15 mg/70 kg body weight fentanyl, sufentanil was hypnotically more potent from fentanyl. 3. Sufentanil acts more powerfully on the respiratory regulation than does fentanyl. Periods of apnoea occur more frequently but can be interrupted by external psychophysiological stimulation. 4. The evaluation of indices of certain EEG-waves, characterizing well defined electroencephalographic stages corresponding to the waking-sleeping-behaviour confirmed the visual over-all analysis of the EEG-stages. 5. Physiological observations on heartrate, systemic blood pressure, rapid eye movements during wakefulness, and slow eye movements during sleepiness showed no reliable differences between sufentanil and fentanil. The systematically documented symptoms and vegetative signs of subjects also showed neither differences nor side-effects.", "contents": "[The hypnotic effect of fentanyl and sulfentanil. An electro-encephalographic comparison (author's transl)]. 1. Electroencephalographic activity was registered in healthy subjects before, during and 90 minutes after intravenous injections of sufentanil and fentanyl. 2. With a dosage of ratio of 1:10, i.e., 0.025 mg/70 kg body weight sufentanil: 0.25 mg/70 kg body weight fentanyl as well as 0.015 mg/70 kg body weight sufentanil: 0.15 mg/70 kg body weight fentanyl, sufentanil was hypnotically more potent from fentanyl. 3. Sufentanil acts more powerfully on the respiratory regulation than does fentanyl. Periods of apnoea occur more frequently but can be interrupted by external psychophysiological stimulation. 4. The evaluation of indices of certain EEG-waves, characterizing well defined electroencephalographic stages corresponding to the waking-sleeping-behaviour confirmed the visual over-all analysis of the EEG-stages. 5. Physiological observations on heartrate, systemic blood pressure, rapid eye movements during wakefulness, and slow eye movements during sleepiness showed no reliable differences between sufentanil and fentanil. The systematically documented symptoms and vegetative signs of subjects also showed neither differences nor side-effects."}
{"id": "PMID:196527", "title": "Histochemical studies on the spinal cord of the Indian buffalo (Bubalus bubalis).", "content": "The distribution pattern of glycogen, alkaline phosphatase and acid phosphatase has been studied and recorded in normal and operated spinal cord of the Indian buffalo (Bubalus bubalis). Based on the observations, the following conclusions have been arrived at i) Glycogen is present in the cytoplasm and on the surface of the spinal neurons. Following injury, it is depleted from these sites. ii) Alkaline phosphatase is located in the nucleus and on the neuronal surface. It is not traceable at these sites following spinal cord injury. iii) Acid phosphatase is mostly confined to the neuronal cytoplasm and tends to increase in injured neurons.", "contents": "Histochemical studies on the spinal cord of the Indian buffalo (Bubalus bubalis). The distribution pattern of glycogen, alkaline phosphatase and acid phosphatase has been studied and recorded in normal and operated spinal cord of the Indian buffalo (Bubalus bubalis). Based on the observations, the following conclusions have been arrived at i) Glycogen is present in the cytoplasm and on the surface of the spinal neurons. Following injury, it is depleted from these sites. ii) Alkaline phosphatase is located in the nucleus and on the neuronal surface. It is not traceable at these sites following spinal cord injury. iii) Acid phosphatase is mostly confined to the neuronal cytoplasm and tends to increase in injured neurons."}
{"id": "PMID:196529", "title": "Difficult lesions of the carotid arteries and their surgical management.", "content": "We have discussed five lesions that are encounted less commonly than the usual occlusive carotid lesion that occurs at the carotid bifurcation, namely, high lesions, ulcerative plaques, tortuous carotids, carotid aneurysms, and carotid body tumors. Illustrative cases of these lesions were presented. The diagnostic difficulties related to some of them and the technicalaspects of their surgical management were discussed. New techniques for resecting internal carotid aneurysms and carotid body tumors by using autogenous saphenous vein grafts and a shunt were described and illustrated.", "contents": "Difficult lesions of the carotid arteries and their surgical management. We have discussed five lesions that are encounted less commonly than the usual occlusive carotid lesion that occurs at the carotid bifurcation, namely, high lesions, ulcerative plaques, tortuous carotids, carotid aneurysms, and carotid body tumors. Illustrative cases of these lesions were presented. The diagnostic difficulties related to some of them and the technicalaspects of their surgical management were discussed. New techniques for resecting internal carotid aneurysms and carotid body tumors by using autogenous saphenous vein grafts and a shunt were described and illustrated."}
{"id": "PMID:196531", "title": "Immunodiffusion test for ovine progressive pneumonia.", "content": "An agar gel immunodiffusion test was developed to detect precipitating antibody against ovine progressive pneumonia (OPP) virus. The test was conducted in plastic petri dishes containing 6 ml of 1% purified agar in tris buffer and 8% sodium chloride. Wells for serum and antigen were 8 mm in diameter and were cut in a hexagonal pattern 3 cm from a central well. Tests were read at 24 and 48 hours. Soluble antigen for the test consisted of concentrated nutrient medium removed every 2 weeks from a cell culture persistently infected with isolate WLC 1 of OPP virus. Specificity of results was verified by testing serums from experimentally exposed sheep and appropriate controls. Two lines of precipitate formed with some serums from experimentally inoculated sheep. Serums taken soon after exposure of sheep to the virus and those taken 3 to 4 years after exposure frequently formed only 1 line of precipitate. Of 37 lambs inoculated with OPP virus, 25% of those tested were positive by postinoculation (PI) month 1, 79% of those tested were positive by PI month 3, and all of those tested were positive by PI month 6. The test appears adequate to detect exposure of sheep to OPP virus.", "contents": "Immunodiffusion test for ovine progressive pneumonia. An agar gel immunodiffusion test was developed to detect precipitating antibody against ovine progressive pneumonia (OPP) virus. The test was conducted in plastic petri dishes containing 6 ml of 1% purified agar in tris buffer and 8% sodium chloride. Wells for serum and antigen were 8 mm in diameter and were cut in a hexagonal pattern 3 cm from a central well. Tests were read at 24 and 48 hours. Soluble antigen for the test consisted of concentrated nutrient medium removed every 2 weeks from a cell culture persistently infected with isolate WLC 1 of OPP virus. Specificity of results was verified by testing serums from experimentally exposed sheep and appropriate controls. Two lines of precipitate formed with some serums from experimentally inoculated sheep. Serums taken soon after exposure of sheep to the virus and those taken 3 to 4 years after exposure frequently formed only 1 line of precipitate. Of 37 lambs inoculated with OPP virus, 25% of those tested were positive by postinoculation (PI) month 1, 79% of those tested were positive by PI month 3, and all of those tested were positive by PI month 6. The test appears adequate to detect exposure of sheep to OPP virus."}
{"id": "PMID:196532", "title": "Broad antigenicity exhibited by some isolates of avian adenovirus.", "content": "Ten of 16 isolates of avian adenovirus could be readily classified as members of serotypes 2, 5, or 7. However, 6 exhibited broad neutralization reactions which created typing problems. Detailed studies of these interactions revealed that our prototype for serotype 5 (i.e., T-8; subsequently found to be an \"intermediate\" strain) contributed to this broad cross-reactivity because it shared antigens with members of serotypes 5 and 7. As a result of this study, TR-59 or 58-1 is recommended as the suitable prototype for the serotype 5 viruses. The 6 broadly reactive isolates were classified as serologic \"variants\" of serotypes 5 and 7.", "contents": "Broad antigenicity exhibited by some isolates of avian adenovirus. Ten of 16 isolates of avian adenovirus could be readily classified as members of serotypes 2, 5, or 7. However, 6 exhibited broad neutralization reactions which created typing problems. Detailed studies of these interactions revealed that our prototype for serotype 5 (i.e., T-8; subsequently found to be an \"intermediate\" strain) contributed to this broad cross-reactivity because it shared antigens with members of serotypes 5 and 7. As a result of this study, TR-59 or 58-1 is recommended as the suitable prototype for the serotype 5 viruses. The 6 broadly reactive isolates were classified as serologic \"variants\" of serotypes 5 and 7."}
{"id": "PMID:196533", "title": "Recovery of reovirus type 2 from an immature dog with respiratory tract disease.", "content": "Two similar cytopathic agents were recovered from the throat and rectal swab specimens of an immature dog with upper respiratory tract disease. The reference isolate, 14-72R, was shown to be a member of the reovirus group by its physicochemical properties, cytopathic effects in cell cultures, and appearance when examined in the electron microscope. Both isolates hemagglutinated human type O erythrocytes and antigenically were closely related to reovirus type 2. The affected pup had an increase in antibody titer to reovirus types 2 and 3. The latter findings provide evidence for possible heterotypic antibody responses in dogs to reovirus infection.", "contents": "Recovery of reovirus type 2 from an immature dog with respiratory tract disease. Two similar cytopathic agents were recovered from the throat and rectal swab specimens of an immature dog with upper respiratory tract disease. The reference isolate, 14-72R, was shown to be a member of the reovirus group by its physicochemical properties, cytopathic effects in cell cultures, and appearance when examined in the electron microscope. Both isolates hemagglutinated human type O erythrocytes and antigenically were closely related to reovirus type 2. The affected pup had an increase in antibody titer to reovirus types 2 and 3. The latter findings provide evidence for possible heterotypic antibody responses in dogs to reovirus infection."}
{"id": "PMID:196534", "title": "Cutaneous abscesses. Anaerobic and aerobic bacteriology and outpatient management.", "content": "Specimens from 135 cutaneous abscesses in outpatients were cultured anaerobically and aerobically. Of these, 4% were sterile and 29% yielded pure cultures, predominantly of Staphylococcus aureus. Aerobic species were isolated from all anatomic areas. Anaerobes were found with a frequency comparable to aerobes in all nonperineal areas except the hand. In contrast, abscesses in the perineal region contained a greater variety and frequency of anaerobes. Only two patients were febrile. All abscesses were treated with incision and drainage, and all healed without complication, including those 74% that were treated without adjunctive antibiotics. Primary management of cutaneous abscesses should be incision and drainage. In general, routine culture and antibiotic therapy are not indicated for localized abscesses in patients with presumably normal host defenses.", "contents": "Cutaneous abscesses. Anaerobic and aerobic bacteriology and outpatient management. Specimens from 135 cutaneous abscesses in outpatients were cultured anaerobically and aerobically. Of these, 4% were sterile and 29% yielded pure cultures, predominantly of Staphylococcus aureus. Aerobic species were isolated from all anatomic areas. Anaerobes were found with a frequency comparable to aerobes in all nonperineal areas except the hand. In contrast, abscesses in the perineal region contained a greater variety and frequency of anaerobes. Only two patients were febrile. All abscesses were treated with incision and drainage, and all healed without complication, including those 74% that were treated without adjunctive antibiotics. Primary management of cutaneous abscesses should be incision and drainage. In general, routine culture and antibiotic therapy are not indicated for localized abscesses in patients with presumably normal host defenses."}
{"id": "PMID:196536", "title": "Enzymatic oxidation of diethyldithiocarbamate by xanthine oxidase and its colorimetric assay.", "content": "Diethyldithiocarbamate is oxidized in vitro by purified cream xanthine oxidase in the presence of nitro blue tetrazolium and phenazine methosulfate. Disulfiram is formed during the enzymatic or nonenzymatic oxidation. When diethyldithiocarbamate is mixed nonenzymatically with nitro blue tetrazolium, the dye is rapidly reduced, but only in the presence of certain organic solvents. This reaction can be used as a convenient colorimetric assay for diethyldithiocarbamate, which gives a stable color over a wide concentration range.", "contents": "Enzymatic oxidation of diethyldithiocarbamate by xanthine oxidase and its colorimetric assay. Diethyldithiocarbamate is oxidized in vitro by purified cream xanthine oxidase in the presence of nitro blue tetrazolium and phenazine methosulfate. Disulfiram is formed during the enzymatic or nonenzymatic oxidation. When diethyldithiocarbamate is mixed nonenzymatically with nitro blue tetrazolium, the dye is rapidly reduced, but only in the presence of certain organic solvents. This reaction can be used as a convenient colorimetric assay for diethyldithiocarbamate, which gives a stable color over a wide concentration range."}
{"id": "PMID:196537", "title": "Studies on the effects of pyrogallol and the structurally related dopa decarboxylase inhibitor RO4-4602 on acetaldehyde metabolism.", "content": "Microanalytic procedures for the determination of AcH in whole blood from EtOH-intoxicated animals given PG or related drugs should utilize a hemolysis step in 0.5 N PCA in order to inhibit PG-dependent AcH production in vitro. Thiourea may also be included as an added protective measure. RO4-4602, a clinically important drug that contains a PG ring structure, is a moderate in vitro inhibitor of AldDH activity, comparable in potency to PG, chloral hydrate, or diethyldithiocarbamate.", "contents": "Studies on the effects of pyrogallol and the structurally related dopa decarboxylase inhibitor RO4-4602 on acetaldehyde metabolism. Microanalytic procedures for the determination of AcH in whole blood from EtOH-intoxicated animals given PG or related drugs should utilize a hemolysis step in 0.5 N PCA in order to inhibit PG-dependent AcH production in vitro. Thiourea may also be included as an added protective measure. RO4-4602, a clinically important drug that contains a PG ring structure, is a moderate in vitro inhibitor of AldDH activity, comparable in potency to PG, chloral hydrate, or diethyldithiocarbamate."}
{"id": "PMID:196538", "title": "Pattern of muscle and nerve pathology in alcoholism.", "content": "One hundred and ninety-one inpatients undergoing detoxification from alcoholism were studied electrodiagnostically. Of them, 115 (57%) exhibited muscle pathology; only 11 (5%) showed no electrodiagnostic evidence of pathology. A common occurrence in the more severely toxic patients was a phenomenon called \"burst suppression,\" which revealed an inability of the patient to sustain a normal consistent firing of motor units upon muscle contration; the significance of this phenomenon is not thoroughly understood. Electrodiagnosis is a helpful tool in the diagnosis, prognosis, treatment, and follow-up of patients with alcoholism.", "contents": "Pattern of muscle and nerve pathology in alcoholism. One hundred and ninety-one inpatients undergoing detoxification from alcoholism were studied electrodiagnostically. Of them, 115 (57%) exhibited muscle pathology; only 11 (5%) showed no electrodiagnostic evidence of pathology. A common occurrence in the more severely toxic patients was a phenomenon called \"burst suppression,\" which revealed an inability of the patient to sustain a normal consistent firing of motor units upon muscle contration; the significance of this phenomenon is not thoroughly understood. Electrodiagnosis is a helpful tool in the diagnosis, prognosis, treatment, and follow-up of patients with alcoholism."}
{"id": "PMID:196544", "title": "[Derivatographic analysis of 6-beta-[(hexahydro-1H-azepin-1-yl) methylenamino]penicillanic acid].", "content": "Derivatographic analysis of 5 samples of 6-beta-(hexahydro-IH-azepin-I-yl)methylenamino penicillanic acid was performed. In addition to the antibiotic the samples had water and acetone in their composition. No effects associated with changes in the physical and chemical state of the substance were observed on the derivatogramme of the samples containing 0.2 and 0.8 per cent of water up 140 degrees C. With a further increase in the temperature an exothermic effect was observed with maximum at 152--153 degrees C connected with melting and chemical degradation of the substance. The derivatogrammes of the samples containing 89--96.4 per cent of the antibiotic were characterized by an endothermic effect with minimum at 65 degrees C caused by evaporation of acetone and partially water from them and by an exothermic effect with maximum at 120 degrees C practically not accompanied by any change in the weight resulting from chemical interaction of the antibiotic with water. The study showed sensitivity of 6-beta-(hexahydro-IH-azepin-I-yl)methylenaminopenicillanic acid to the presence of even insignificant amounts of water in it, maximum elimination of which from the antibiotic is an important factor of increasing its stability.", "contents": "[Derivatographic analysis of 6-beta-[(hexahydro-1H-azepin-1-yl) methylenamino]penicillanic acid]. Derivatographic analysis of 5 samples of 6-beta-(hexahydro-IH-azepin-I-yl)methylenamino penicillanic acid was performed. In addition to the antibiotic the samples had water and acetone in their composition. No effects associated with changes in the physical and chemical state of the substance were observed on the derivatogramme of the samples containing 0.2 and 0.8 per cent of water up 140 degrees C. With a further increase in the temperature an exothermic effect was observed with maximum at 152--153 degrees C connected with melting and chemical degradation of the substance. The derivatogrammes of the samples containing 89--96.4 per cent of the antibiotic were characterized by an endothermic effect with minimum at 65 degrees C caused by evaporation of acetone and partially water from them and by an exothermic effect with maximum at 120 degrees C practically not accompanied by any change in the weight resulting from chemical interaction of the antibiotic with water. The study showed sensitivity of 6-beta-(hexahydro-IH-azepin-I-yl)methylenaminopenicillanic acid to the presence of even insignificant amounts of water in it, maximum elimination of which from the antibiotic is an important factor of increasing its stability."}
{"id": "PMID:196545", "title": "[Mechanism of penicillinase inhibition by alkyl sulfates in the presence of synthetic polyeletrolytes].", "content": "Competing inhibition of Bacillus licheniformis 749/C penicillinase by alkylsulfates CnH2n+ 1OSO3N1 where n was 8--16 was studied. The values of the inhibition constants Ki of individual homologues were estimated. It was shown that stability of complex \"enzyme-inhibitor\" increased with lengthening of the hydrocarbon radical which was probably due to increased hydrophobic interaction of the alkyl radical with the lipophilic areas of the penicillinase active center. Inhibition in the presence of sopolymers of vinylpirrolidone with N-alkylvinylamine was studied with the aim of modeling the process of penicillinase inhibitions by alkylsulfates in the presence of the blood serum. It was shown that polyelectrolytes posessing hydrophobic substituents had an ability of reducing the activity of inhibited penicillinase, cooperative transfer of alkylsulfate molecules from the enzyme to polyelectrolyte being observed. The maximum effect was registered in the polyelectrolytes with substituents C12H25 and C16H33 which was confirmed in the experiments with the penicillinase-producing strains of staphylococci.", "contents": "[Mechanism of penicillinase inhibition by alkyl sulfates in the presence of synthetic polyeletrolytes]. Competing inhibition of Bacillus licheniformis 749/C penicillinase by alkylsulfates CnH2n+ 1OSO3N1 where n was 8--16 was studied. The values of the inhibition constants Ki of individual homologues were estimated. It was shown that stability of complex \"enzyme-inhibitor\" increased with lengthening of the hydrocarbon radical which was probably due to increased hydrophobic interaction of the alkyl radical with the lipophilic areas of the penicillinase active center. Inhibition in the presence of sopolymers of vinylpirrolidone with N-alkylvinylamine was studied with the aim of modeling the process of penicillinase inhibitions by alkylsulfates in the presence of the blood serum. It was shown that polyelectrolytes posessing hydrophobic substituents had an ability of reducing the activity of inhibited penicillinase, cooperative transfer of alkylsulfate molecules from the enzyme to polyelectrolyte being observed. The maximum effect was registered in the polyelectrolytes with substituents C12H25 and C16H33 which was confirmed in the experiments with the penicillinase-producing strains of staphylococci."}
{"id": "PMID:196546", "title": "Antiviral activity of 3-deazaguanine, 3-deazaguanosine, and 3-deazaguanylic acid.", "content": "3-Deazaguanine (ICN 4221), 3-deazaguanosine (ICN 4793), and 3-deazaguanylic acid (ICN 5412) represent a new class of synthetic guanine analogs having antiviral activity. In vitro, nine ribonucleic acid and seven deoxyribonucleic acid viruses were inhibited, including influenza, parainfluenza, rhino-, vesicular stomatitis, adeno-, herpes-, cytomegalo-, vaccinia, pseudorabies, and myxoma viruses. They were effective orally against influenza types A and B and parainfluenza type 1 (Sendai) virus infections in mice, with a therapeutic index of 16 against the latter two viruses. The course of herpes encephalitis was altered only when the drugs were applied directly into the brain. In addition, these drugs were effective inhibitors of Friend leukemia virus-induced splenomegaly in mice; treatment also produced extensions of life in these animals.", "contents": "Antiviral activity of 3-deazaguanine, 3-deazaguanosine, and 3-deazaguanylic acid. 3-Deazaguanine (ICN 4221), 3-deazaguanosine (ICN 4793), and 3-deazaguanylic acid (ICN 5412) represent a new class of synthetic guanine analogs having antiviral activity. In vitro, nine ribonucleic acid and seven deoxyribonucleic acid viruses were inhibited, including influenza, parainfluenza, rhino-, vesicular stomatitis, adeno-, herpes-, cytomegalo-, vaccinia, pseudorabies, and myxoma viruses. They were effective orally against influenza types A and B and parainfluenza type 1 (Sendai) virus infections in mice, with a therapeutic index of 16 against the latter two viruses. The course of herpes encephalitis was altered only when the drugs were applied directly into the brain. In addition, these drugs were effective inhibitors of Friend leukemia virus-induced splenomegaly in mice; treatment also produced extensions of life in these animals."}
{"id": "PMID:196547", "title": "Uptake of glucose and maltose by Bacillus popillae.", "content": "Results of experiments with glucose and its analog, methyl alpha-D-glucopyranoside, indicated that when glucose was present at low concentrations, it was transported into Bacillus popilliae NRRL B-2309MC cells as glucose 6-phosphate by a phosphoenolpyruvate:sugar phosphotransferase system. An additional mode(s) of entry may be operative at higher glucose concentrations. Maltose appeared to enter the cells by a nonphosphorylative process and was hydrolyzed intracellularly to glucose. No phosphoryl donor was necessary for this hydrolysis.", "contents": "Uptake of glucose and maltose by Bacillus popillae. Results of experiments with glucose and its analog, methyl alpha-D-glucopyranoside, indicated that when glucose was present at low concentrations, it was transported into Bacillus popilliae NRRL B-2309MC cells as glucose 6-phosphate by a phosphoenolpyruvate:sugar phosphotransferase system. An additional mode(s) of entry may be operative at higher glucose concentrations. Maltose appeared to enter the cells by a nonphosphorylative process and was hydrolyzed intracellularly to glucose. No phosphoryl donor was necessary for this hydrolysis."}
{"id": "PMID:196548", "title": "Aflatoxin in corn: ammonia inactivation and bioassay with rainbow trout.", "content": "Four samples of corn were compared with respect to their hepatocarcinogenicity in rainbow trout. One corn sample was found by chemical analysis to contain no detectable aflatoxin. A second sample was contaminated with aflatoxins at a level of 180 microgram/kg. Each of the above-mentioned samples was divided, and one-half of each was ammoniated. These four samples were added to a semipurified basal diet and fed to a sensitive strain of rainbow trout. It was found that ammoniation inactivated the aflatoxins and reduced the carcinogenicity of the contaminated corn to a level that was not significantly different from that with the basal control diet. It was also found that the ammoniation process did not reduce the nutritive value of the corn.", "contents": "Aflatoxin in corn: ammonia inactivation and bioassay with rainbow trout. Four samples of corn were compared with respect to their hepatocarcinogenicity in rainbow trout. One corn sample was found by chemical analysis to contain no detectable aflatoxin. A second sample was contaminated with aflatoxins at a level of 180 microgram/kg. Each of the above-mentioned samples was divided, and one-half of each was ammoniated. These four samples were added to a semipurified basal diet and fed to a sensitive strain of rainbow trout. It was found that ammoniation inactivated the aflatoxins and reduced the carcinogenicity of the contaminated corn to a level that was not significantly different from that with the basal control diet. It was also found that the ammoniation process did not reduce the nutritive value of the corn."}
{"id": "PMID:196549", "title": "Inheritance and longevity of infectious pancreatic necrosis virus in the zebra fish, Brachydanio rerio (Hamilton-Buchanan).", "content": "Zebra fish (Brachydanio rerio) were injected with infectious pancreatic necrosis virus (IPNV) and then spawned to determine whether the virus was passed on to the eggs, and if it was, how long it remained in the free-swimming F1. The mating variations included parents receiving one or two injections of virus, and within these categories, matings in which both parents were treated or only one parent was treated. The results showed that transmission of IPNV to the egg did occur, and that this transmission was via the female alone. However, if the female was allowed to produce antibodies to the virus, as when she received two injections of IPNV, she transmitted the virus to the eggs for only a short period of time. In addition, when the virus was transmitted to the egg, it remained in the free-swimming F1 for a period of at least 5 months.", "contents": "Inheritance and longevity of infectious pancreatic necrosis virus in the zebra fish, Brachydanio rerio (Hamilton-Buchanan). Zebra fish (Brachydanio rerio) were injected with infectious pancreatic necrosis virus (IPNV) and then spawned to determine whether the virus was passed on to the eggs, and if it was, how long it remained in the free-swimming F1. The mating variations included parents receiving one or two injections of virus, and within these categories, matings in which both parents were treated or only one parent was treated. The results showed that transmission of IPNV to the egg did occur, and that this transmission was via the female alone. However, if the female was allowed to produce antibodies to the virus, as when she received two injections of IPNV, she transmitted the virus to the eggs for only a short period of time. In addition, when the virus was transmitted to the egg, it remained in the free-swimming F1 for a period of at least 5 months."}
{"id": "PMID:196558", "title": "Eczema herpeticum caused by herpesvirus type 2. A case in a patient with Darier disease.", "content": "This, to our knowledge, is the first documented report of eczema herpeticum due to infection with herpesvirus hominis type 2. The virus was isolated from a patient with known Darier disease who developed Kaposi varicelliform eruption. Recent increases in the incidence of infection with type 2 herpes simplex as well as the high frequency of recurrence with this virus make this infection of potential significance in patients with preexisting cutaneous disease.", "contents": "Eczema herpeticum caused by herpesvirus type 2. A case in a patient with Darier disease. This, to our knowledge, is the first documented report of eczema herpeticum due to infection with herpesvirus hominis type 2. The virus was isolated from a patient with known Darier disease who developed Kaposi varicelliform eruption. Recent increases in the incidence of infection with type 2 herpes simplex as well as the high frequency of recurrence with this virus make this infection of potential significance in patients with preexisting cutaneous disease."}
{"id": "PMID:196559", "title": "Sporotrichoid leishmaniasis.", "content": "American leishmaniasis that is acquired in Panama may appear clinically as a sporotrichoid eruption. When leisons reminiscent of sporotrichosis are encountered, a careful history of the patient's travels should be made, as well as a search for the organism of leischmaniasis in tissue smears, histopathological sections, and cultured media. We report the case of an American soldier stationed in Panama who had developed an ulcer on the dorsum of his right wrist, and nodules on his right forearm that were arranged in a linear pattern. The initial clinical impression was that of sporotrichosis, but on careful study of the patient's history, and after other appropriate investigations were made, it was discovered that the patient had leishmaniasis.", "contents": "Sporotrichoid leishmaniasis. American leishmaniasis that is acquired in Panama may appear clinically as a sporotrichoid eruption. When leisons reminiscent of sporotrichosis are encountered, a careful history of the patient's travels should be made, as well as a search for the organism of leischmaniasis in tissue smears, histopathological sections, and cultured media. We report the case of an American soldier stationed in Panama who had developed an ulcer on the dorsum of his right wrist, and nodules on his right forearm that were arranged in a linear pattern. The initial clinical impression was that of sporotrichosis, but on careful study of the patient's history, and after other appropriate investigations were made, it was discovered that the patient had leishmaniasis."}
{"id": "PMID:196561", "title": "The hepatic ultrastructure of chlordene-fed pigeons.", "content": "Adult male pigeons were fed 500 ppm of nontoxic chlordene per day for 6 weeks. The ultrastructure of hepatic cells of treated pigeons was examined and compared with that of the control birds. Chlordene feeding induced cytological changes in the structure of liver cells. Thinning of the microvilli of bile canaliculi and clear marking of fibrous long spacing and non-fibrous segment long spacing on collagen fibers were noticed. Increase in the number as well as the vacuolation of lipid bodies in certain portions of the cytoplasm, presence of myeloid bodies in mitochondria, and an increase in the smooth-surfaced endoplasmic reticulum were observed in the liver cells of pigeons given chlordene.", "contents": "The hepatic ultrastructure of chlordene-fed pigeons. Adult male pigeons were fed 500 ppm of nontoxic chlordene per day for 6 weeks. The ultrastructure of hepatic cells of treated pigeons was examined and compared with that of the control birds. Chlordene feeding induced cytological changes in the structure of liver cells. Thinning of the microvilli of bile canaliculi and clear marking of fibrous long spacing and non-fibrous segment long spacing on collagen fibers were noticed. Increase in the number as well as the vacuolation of lipid bodies in certain portions of the cytoplasm, presence of myeloid bodies in mitochondria, and an increase in the smooth-surfaced endoplasmic reticulum were observed in the liver cells of pigeons given chlordene."}
{"id": "PMID:196563", "title": "Location of three key enzymes of gluconeogenesis in baker's yeast.", "content": "The subcellular location of hexose diphosphatase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase in baker's yeast (Saccharomyces cerevisiae) was investigated by density gradient centrifugation of spheroplast lysates obtained by osmotic shock treatment of spheroplasts and centrifugation for 10000 g x min. On the evidence obtained from zonal separations these three enzymes of gluconeogenesis are most probably located in the soluble cytosol.", "contents": "Location of three key enzymes of gluconeogenesis in baker's yeast. The subcellular location of hexose diphosphatase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase in baker's yeast (Saccharomyces cerevisiae) was investigated by density gradient centrifugation of spheroplast lysates obtained by osmotic shock treatment of spheroplasts and centrifugation for 10000 g x min. On the evidence obtained from zonal separations these three enzymes of gluconeogenesis are most probably located in the soluble cytosol."}
{"id": "PMID:196564", "title": "[Cerebral tumors of primitive germinal origin].", "content": "The authors attempt to justify the term cerebral tumour of primitive germinal origin from four of their own cases and a review of the literature. They emphasise the specific features. The tumours are more common in boys and involve the pineal, the walls of the third ventricle, the hypothalamus and the posterior pituitary. Several histological types may be distinguished by the degree of differentiation but the stromal reaction, which is partly responsible for the symptoms, is always present. The clinical course of the illness is biphasic. The first is manifest by endocrine disorders and is of relatively long duration. Water homeostasis is always affected and may be associated with other hypothalamic disorders. In the second phase, neurological symptoms and raised intracranial pressure appear. Surgical removal is not always possible, but radiotherapy improves the outlook.", "contents": "[Cerebral tumors of primitive germinal origin]. The authors attempt to justify the term cerebral tumour of primitive germinal origin from four of their own cases and a review of the literature. They emphasise the specific features. The tumours are more common in boys and involve the pineal, the walls of the third ventricle, the hypothalamus and the posterior pituitary. Several histological types may be distinguished by the degree of differentiation but the stromal reaction, which is partly responsible for the symptoms, is always present. The clinical course of the illness is biphasic. The first is manifest by endocrine disorders and is of relatively long duration. Water homeostasis is always affected and may be associated with other hypothalamic disorders. In the second phase, neurological symptoms and raised intracranial pressure appear. Surgical removal is not always possible, but radiotherapy improves the outlook."}
{"id": "PMID:196565", "title": "[Severe viral pneumonia. A radiological classification with prognostic value].", "content": "In one year eighteen children were admitted to an intensive care unit with severe viral pneumonia. Four groups were identified by the appearance of the chest X-ray. Bronchiolitis was seen in eight patients, alveolitis in four, interstitial pneumonia in two and combined bronchiolitis and alveolitis in four. Three of the four children with alveolitis died and six of the twelve with bronchiolitis, alone or with alveolitis, had residual bronchial obstruction.", "contents": "[Severe viral pneumonia. A radiological classification with prognostic value]. In one year eighteen children were admitted to an intensive care unit with severe viral pneumonia. Four groups were identified by the appearance of the chest X-ray. Bronchiolitis was seen in eight patients, alveolitis in four, interstitial pneumonia in two and combined bronchiolitis and alveolitis in four. Three of the four children with alveolitis died and six of the twelve with bronchiolitis, alone or with alveolitis, had residual bronchial obstruction."}
{"id": "PMID:196566", "title": "[Bone maturation in the fetus and newborn infant].", "content": "On the basis of a study of X-ray films of the lower limbs of 994 babies (included 245 hypotrophics) a \"bone age\" scale of the fetus between 28 and 42 weeks of gestation has been established. The Acheson's method has been used and the bone age determined by addition of notes given to different evolutive phases of the first five ossification centers of the ankle and the knee. To more practical purpose, the results of boys and girls have been joined, although the bone age is in advance among the girls and a theorical scale established with the 10th, 50th and 90th percentiles curves. The comparison with the curves established among 245 hypotrophic newborns, seems to prove that the bone age is a more resistant criteria to malnutrition than the weight and even the length. This new criteria to determine the fetal age does not escape to the criticisms given to the other existing criteria, but radiograph is an objective and fixed document. Its repetition allows to follow the growth of the child and probably to study the role of various factors, mainly nutritional, on this growth. The measure of the length of the tibia and of its increament on the same X-ray films is an other possible method of great interest for the same purpose.", "contents": "[Bone maturation in the fetus and newborn infant]. On the basis of a study of X-ray films of the lower limbs of 994 babies (included 245 hypotrophics) a \"bone age\" scale of the fetus between 28 and 42 weeks of gestation has been established. The Acheson's method has been used and the bone age determined by addition of notes given to different evolutive phases of the first five ossification centers of the ankle and the knee. To more practical purpose, the results of boys and girls have been joined, although the bone age is in advance among the girls and a theorical scale established with the 10th, 50th and 90th percentiles curves. The comparison with the curves established among 245 hypotrophic newborns, seems to prove that the bone age is a more resistant criteria to malnutrition than the weight and even the length. This new criteria to determine the fetal age does not escape to the criticisms given to the other existing criteria, but radiograph is an objective and fixed document. Its repetition allows to follow the growth of the child and probably to study the role of various factors, mainly nutritional, on this growth. The measure of the length of the tibia and of its increament on the same X-ray films is an other possible method of great interest for the same purpose."}
{"id": "PMID:196567", "title": "Alteration of cell surfaces with increased tumorigenicity.", "content": "A comparison of four mouse tumorigenic cell lines derived from transformed peritoneal macrophages is reported. Tumorigenicity of various cell concentration inocula was compared with their saturation densities, agglutinability by Con A, and their surface morphologies as revealed by SEM. It is shown that increase in tumorigenicity after repeated passage through syngeneic mice is associated with changes in their growth characteristics, Con A agglutinability, and correlates with surface changes observed by SEM. The results show that after repeated transfer of transformed cells in syngeneic mice the cells become more tumorigenic, have a higher degree of agglutinability, and show progressive changes of their surface morphology.", "contents": "Alteration of cell surfaces with increased tumorigenicity. A comparison of four mouse tumorigenic cell lines derived from transformed peritoneal macrophages is reported. Tumorigenicity of various cell concentration inocula was compared with their saturation densities, agglutinability by Con A, and their surface morphologies as revealed by SEM. It is shown that increase in tumorigenicity after repeated passage through syngeneic mice is associated with changes in their growth characteristics, Con A agglutinability, and correlates with surface changes observed by SEM. The results show that after repeated transfer of transformed cells in syngeneic mice the cells become more tumorigenic, have a higher degree of agglutinability, and show progressive changes of their surface morphology."}
{"id": "PMID:196568", "title": "Introductory studies on metabolism of free glucose in aqueous extracts from smooth muscles of the stomach of geese and ducks.", "content": "Aqueous extracts from smooth muscles of the stomachs of geese and ducks contain enzyme systems which not only oxidize free D-glucose, but also determine its further metabolism. The successive metabolites are probably 1,5-D-gluconolactone and 2-ketogluconic acid, and the final product is either pyruvic acid of alpha-ketoglutaric acid. Better understanding of this metabolism will require further studies.", "contents": "Introductory studies on metabolism of free glucose in aqueous extracts from smooth muscles of the stomach of geese and ducks. Aqueous extracts from smooth muscles of the stomachs of geese and ducks contain enzyme systems which not only oxidize free D-glucose, but also determine its further metabolism. The successive metabolites are probably 1,5-D-gluconolactone and 2-ketogluconic acid, and the final product is either pyruvic acid of alpha-ketoglutaric acid. Better understanding of this metabolism will require further studies."}
{"id": "PMID:196569", "title": "Acute radiation nephritis. Light and electron microscopic observations.", "content": "Light and electron microscopy were used to observe acute radiation nephritis. By light microscopy the changes were of fibrinoid necrosis of the arteries and atrerioles with segmental necrosis of the glomerular tufts. By electron microscopy the endocapillary cells reacted by hypertrophy and hyperplasia with increase in cytoplasmic organelles. In addition, disruption of endothelial and epithelial cells from the basement membranes were seen. It is concluded that the electron microscopic changes were unique and may be helpful in differentiating the necrotizing glomerulitis seen in other conditions, especially malignant hypertension.", "contents": "Acute radiation nephritis. Light and electron microscopic observations. Light and electron microscopy were used to observe acute radiation nephritis. By light microscopy the changes were of fibrinoid necrosis of the arteries and atrerioles with segmental necrosis of the glomerular tufts. By electron microscopy the endocapillary cells reacted by hypertrophy and hyperplasia with increase in cytoplasmic organelles. In addition, disruption of endothelial and epithelial cells from the basement membranes were seen. It is concluded that the electron microscopic changes were unique and may be helpful in differentiating the necrotizing glomerulitis seen in other conditions, especially malignant hypertension."}
{"id": "PMID:196571", "title": "Further studies on human enteric coronaviruses.", "content": "Comparisons were made between human enteric coronaviruses and the enteric coronaviruses of pigs and calves by negative staining. Examination of human intestinal organ culture fluids at various time intervals after inoculation with the human enteric coronavirus showed increasing numbers of particles in the fluids. Thin sections of the columnar epithelial cells of these explants showed a number of features consistent with the replication of known human and animal coronaviruses. Virus particles found in thin sections had a mean diameter of 68 nm. In addition, a structure was found in thin sections which has not been described previously. This structure may represent the viral nucleocapsid.", "contents": "Further studies on human enteric coronaviruses. Comparisons were made between human enteric coronaviruses and the enteric coronaviruses of pigs and calves by negative staining. Examination of human intestinal organ culture fluids at various time intervals after inoculation with the human enteric coronavirus showed increasing numbers of particles in the fluids. Thin sections of the columnar epithelial cells of these explants showed a number of features consistent with the replication of known human and animal coronaviruses. Virus particles found in thin sections had a mean diameter of 68 nm. In addition, a structure was found in thin sections which has not been described previously. This structure may represent the viral nucleocapsid."}
{"id": "PMID:196572", "title": "Type specificity and use of human sera for rapid typing of herpes simplex virus isolates by an indirect peroxidase-labeled antibody technique: a comparison with three other methods.", "content": "Human sera from patients showing seroconversion following a primary herpes simplex virus type 1 (HSV-1) or HSV type 2 (HSV-2) infection, as well as 19S and 7S fractions obtained from the same sera, have been used for typing 191 HSV isolates by an indirect peroxidase-labeled antibody (PLA) method. Typing has also been performed on all of the isolates using a microneutralization (MN) and the indirect hemagglutination (IHA) inhibition test. Furthermore, 30 isolates have been typed by a plaque method. Results obtained with the PLA method was in complete agreement with those of the other two procedures. The PLA method is rapid and simple, offers easy interpretation and a permanent record of results.", "contents": "Type specificity and use of human sera for rapid typing of herpes simplex virus isolates by an indirect peroxidase-labeled antibody technique: a comparison with three other methods. Human sera from patients showing seroconversion following a primary herpes simplex virus type 1 (HSV-1) or HSV type 2 (HSV-2) infection, as well as 19S and 7S fractions obtained from the same sera, have been used for typing 191 HSV isolates by an indirect peroxidase-labeled antibody (PLA) method. Typing has also been performed on all of the isolates using a microneutralization (MN) and the indirect hemagglutination (IHA) inhibition test. Furthermore, 30 isolates have been typed by a plaque method. Results obtained with the PLA method was in complete agreement with those of the other two procedures. The PLA method is rapid and simple, offers easy interpretation and a permanent record of results."}
{"id": "PMID:196575", "title": "Differences in multiplication of virulent and vaccine strains of poliovirus type I, II, and III in laboratory animals.", "content": "Multiplication of virulent and vaccine strains of poliovirus type I, II and III in laboratory animals of different species was studied comparatively. The main criterion of virus reproduction was the production of the photoresistant virus progeny after inoculation of the animals with proflavin-photosensitized virus strains. On the whole, virulent poliovirus strains were characterized by replication in a wide range of hosts (monkeys, cotton rats, white mice, guinea pigs, rabbits, chickens, chick embryos), a low infective dose, production of the photoresistant progeny to a high titre, clinically overt disease in some animal species. The vaccine strains multiplied in a norrower range of hosts, had a high infective dose, a low titre of virus progeny, and caused no clinical symptoms of infection. These differences may serve as a marker for differentiation between virulent and attenuated strains in vivo. Administration of guanidine before inoculation of newborn cotton rats completely prevented or delayed by several days the production of photoresistant virus progeny. This fact confirms the stability of the proflavin-poliovirus complex under conditions ruling out virus replication.", "contents": "Differences in multiplication of virulent and vaccine strains of poliovirus type I, II, and III in laboratory animals. Multiplication of virulent and vaccine strains of poliovirus type I, II and III in laboratory animals of different species was studied comparatively. The main criterion of virus reproduction was the production of the photoresistant virus progeny after inoculation of the animals with proflavin-photosensitized virus strains. On the whole, virulent poliovirus strains were characterized by replication in a wide range of hosts (monkeys, cotton rats, white mice, guinea pigs, rabbits, chickens, chick embryos), a low infective dose, production of the photoresistant progeny to a high titre, clinically overt disease in some animal species. The vaccine strains multiplied in a norrower range of hosts, had a high infective dose, a low titre of virus progeny, and caused no clinical symptoms of infection. These differences may serve as a marker for differentiation between virulent and attenuated strains in vivo. Administration of guanidine before inoculation of newborn cotton rats completely prevented or delayed by several days the production of photoresistant virus progeny. This fact confirms the stability of the proflavin-poliovirus complex under conditions ruling out virus replication."}
{"id": "PMID:196577", "title": "Isolation of Marek's disease virus DNA from infected cells by electrophoresis on polyacrylamide gels.", "content": "Marek's disease virus DNA isolated from the nuclear fraction of infected chicken embryo fibroblasts and sucrose-purified particles was electrophoresed on 3 per cent polyacrylamide gels and was compared in its electrophoretical behaviour with isolated pseudorabies and herpes simplex DNA, strain HF. The DNA molecules eluted from the gel were identified by their sedimentation coefficient (53--55S) and buoyant density (1.707 g/ml) to be of viral origin. MDV DNA molecules were electrophoretically also detected and identified in DNA preparations of the lymphoblastoid Marek's disease tumour cell line MSB-1 which therefore has to be considered as a producer line. The electrophoresis of DNA preparations from Marek's disease virus-infected cells on polyacrylamide gels provides a semipreparative method for the isolation of MDV DNA.", "contents": "Isolation of Marek's disease virus DNA from infected cells by electrophoresis on polyacrylamide gels. Marek's disease virus DNA isolated from the nuclear fraction of infected chicken embryo fibroblasts and sucrose-purified particles was electrophoresed on 3 per cent polyacrylamide gels and was compared in its electrophoretical behaviour with isolated pseudorabies and herpes simplex DNA, strain HF. The DNA molecules eluted from the gel were identified by their sedimentation coefficient (53--55S) and buoyant density (1.707 g/ml) to be of viral origin. MDV DNA molecules were electrophoretically also detected and identified in DNA preparations of the lymphoblastoid Marek's disease tumour cell line MSB-1 which therefore has to be considered as a producer line. The electrophoresis of DNA preparations from Marek's disease virus-infected cells on polyacrylamide gels provides a semipreparative method for the isolation of MDV DNA."}
{"id": "PMID:196578", "title": "Prevalence of type-specific antibody against type 1 and type 2 herpes simplex virus in women with abnormal cervical cytology: evidence towards pre-pubertal vaccination of sero-negative female subjects.", "content": "Patients with abnormal cervical cytology demonstrated a higher prevalence of type-specific complement-fixing antibody to type 2 herpes simplex virus than patients with negative cervical cytology and patients with carcinoma of other body sites. Case-control differences were apparent irrespective of age, socio-economic class and marital status. By contrast, case groups demonstrated a lower prevalence of subjects with type 1 specific antibody. This raises the possibility that pre-adolescent exposure to type 1 herpes simplex virus may offer some measure of protection against pre-malignant and malignant cervical pathology.", "contents": "Prevalence of type-specific antibody against type 1 and type 2 herpes simplex virus in women with abnormal cervical cytology: evidence towards pre-pubertal vaccination of sero-negative female subjects. Patients with abnormal cervical cytology demonstrated a higher prevalence of type-specific complement-fixing antibody to type 2 herpes simplex virus than patients with negative cervical cytology and patients with carcinoma of other body sites. Case-control differences were apparent irrespective of age, socio-economic class and marital status. By contrast, case groups demonstrated a lower prevalence of subjects with type 1 specific antibody. This raises the possibility that pre-adolescent exposure to type 1 herpes simplex virus may offer some measure of protection against pre-malignant and malignant cervical pathology."}
{"id": "PMID:196579", "title": "Improvement of arbovirus HA antigens by treatment with a colloidal silica gel and sonication.", "content": "A remarkable increase in HA titers for weakly haemagglutinating Norwegian arbovirus strains, Uukuniemi and Runde viruses, was achieved by including treatment with the colloidal silica gel Aerosil in the antigen preparation scheme. By combining this procedure with sonication, the titers of sucrose-aceton extracted, infected suckling mouse brains could be increased several hundred times. Good antigens also were obtained from virus grown in BHK21/c 13 cell cultures and concentrated by polyethylene glycol 6000/NaCl. Rubella virus HA antigen and HBsAg were adsorbed to the gel, and excluded from a preparation by treatment with Aerosil. This indicates a limitation to the universal use of the method, presumably related to the particle size.", "contents": "Improvement of arbovirus HA antigens by treatment with a colloidal silica gel and sonication. A remarkable increase in HA titers for weakly haemagglutinating Norwegian arbovirus strains, Uukuniemi and Runde viruses, was achieved by including treatment with the colloidal silica gel Aerosil in the antigen preparation scheme. By combining this procedure with sonication, the titers of sucrose-aceton extracted, infected suckling mouse brains could be increased several hundred times. Good antigens also were obtained from virus grown in BHK21/c 13 cell cultures and concentrated by polyethylene glycol 6000/NaCl. Rubella virus HA antigen and HBsAg were adsorbed to the gel, and excluded from a preparation by treatment with Aerosil. This indicates a limitation to the universal use of the method, presumably related to the particle size."}
{"id": "PMID:196580", "title": "Analysis of the structure of human papilloma virus DNA.", "content": "Human papilloma virus DNA has been examined for heterogeneity by electron microscopy, reassociation kinetics, and restriction endonuclease digestion. No heterogeneity in contour length was detected. The reassociation rate of papilloma DNA isolated from pooled warts was consistent with that expected for a homogeneous, unique DNA of molecular weight 5 X 10(6). Restriction endonuclease digestions of five papilloma DNA preparations isolated from pooled warts yielded predominantly fragments of the expected sizes, but significant quantities of fragments atypical in size were also commonly produced.", "contents": "Analysis of the structure of human papilloma virus DNA. Human papilloma virus DNA has been examined for heterogeneity by electron microscopy, reassociation kinetics, and restriction endonuclease digestion. No heterogeneity in contour length was detected. The reassociation rate of papilloma DNA isolated from pooled warts was consistent with that expected for a homogeneous, unique DNA of molecular weight 5 X 10(6). Restriction endonuclease digestions of five papilloma DNA preparations isolated from pooled warts yielded predominantly fragments of the expected sizes, but significant quantities of fragments atypical in size were also commonly produced."}
{"id": "PMID:196581", "title": "Blood-to-cerebrospinal fluid barrier for cyclic adenosine monophosphate in man.", "content": "A definite blood to lumbar CSF barrier for cyclic adenosine monophosphate (cAMP) exists in man under physiologic conditions. Lumbar CSF cAMP level remained unchanged, while the CSF glucose level rose significantly after a glucagon hydrochloride infusion that caused a 40-fold increase in the plasma cAMP level.", "contents": "Blood-to-cerebrospinal fluid barrier for cyclic adenosine monophosphate in man. A definite blood to lumbar CSF barrier for cyclic adenosine monophosphate (cAMP) exists in man under physiologic conditions. Lumbar CSF cAMP level remained unchanged, while the CSF glucose level rose significantly after a glucagon hydrochloride infusion that caused a 40-fold increase in the plasma cAMP level."}
{"id": "PMID:196582", "title": "Anterior interosseous nerve syndromes. Diagnostic methods and alternative treatments.", "content": "Electromyographic and nerve conduction studies on 46 normal controls (12 men and 34 women, aged 9 to 67 years) are compared with findings in seven patients (three men and four women, aged 9 to 60 years) with the anterior interosseous nerve (AIN) syndromes, including two patients with bilateral involvement (the first such reported cases, to our knowledge). Routine motor and sensory nerve conduction studies of the radial, median, and ulnar nerves show no difference between controls and patients. In 46 normal controls (84 different AIN studies), the latency and duration of the evoked action potential from elbow to pronator quadratus was 5.1 msec +/- 0.9 (95% confidence interval) and 3.6 msec +/- 1.1 (95% confidence interval), respectively. Five of the seven patients had abnormal latencies from elbow to pronator quadratus while all showed prolonged duration of the action potential. Electromyographic abnormalities of the pronator quadratus, flexor pollicis longus, and flexor digitorum profundi, as well as delayed motor latencies and prolonged duration of the evoked potential of the AIN from elbow to pronator quadratus provide sufficient information to diagnose the AIN syndrome. Surgical exploration may not be necessary unless there is evidence of a penetrating injury, significant entrapment, or certain fractures.", "contents": "Anterior interosseous nerve syndromes. Diagnostic methods and alternative treatments. Electromyographic and nerve conduction studies on 46 normal controls (12 men and 34 women, aged 9 to 67 years) are compared with findings in seven patients (three men and four women, aged 9 to 60 years) with the anterior interosseous nerve (AIN) syndromes, including two patients with bilateral involvement (the first such reported cases, to our knowledge). Routine motor and sensory nerve conduction studies of the radial, median, and ulnar nerves show no difference between controls and patients. In 46 normal controls (84 different AIN studies), the latency and duration of the evoked action potential from elbow to pronator quadratus was 5.1 msec +/- 0.9 (95% confidence interval) and 3.6 msec +/- 1.1 (95% confidence interval), respectively. Five of the seven patients had abnormal latencies from elbow to pronator quadratus while all showed prolonged duration of the action potential. Electromyographic abnormalities of the pronator quadratus, flexor pollicis longus, and flexor digitorum profundi, as well as delayed motor latencies and prolonged duration of the evoked potential of the AIN from elbow to pronator quadratus provide sufficient information to diagnose the AIN syndrome. Surgical exploration may not be necessary unless there is evidence of a penetrating injury, significant entrapment, or certain fractures."}
{"id": "PMID:196583", "title": "A method for characterizing subgroups and related survivals in cancer patients. Application to brain tumors.", "content": "It has long been known that if the probability of dying of a given cancer remains constant over time, the logarithmic plot of survival of a group of patients with that cancer will be a straight line. More frequently, however, the probability of dying varies with time and the logarithmic survival plot is a curve. We believe that in some cases a population of patients with one type of neoplasm may be composed of several subgroups, each of which has a simple predictable course with a rectilinear survival plot. This article describes a method for partitioning such survival plots and identifying and characterizing the subgroups and applies the method to a group of patients with brain tumors. The value of being able to identify these subgroups and their relative proportions, the observations that can be made with this analysis regarding the nature of the various subgroups of brain tumors, and the implications of changes in the half-lives as well as the proportions of the subgroups with time are discussed.", "contents": "A method for characterizing subgroups and related survivals in cancer patients. Application to brain tumors. It has long been known that if the probability of dying of a given cancer remains constant over time, the logarithmic plot of survival of a group of patients with that cancer will be a straight line. More frequently, however, the probability of dying varies with time and the logarithmic survival plot is a curve. We believe that in some cases a population of patients with one type of neoplasm may be composed of several subgroups, each of which has a simple predictable course with a rectilinear survival plot. This article describes a method for partitioning such survival plots and identifying and characterizing the subgroups and applies the method to a group of patients with brain tumors. The value of being able to identify these subgroups and their relative proportions, the observations that can be made with this analysis regarding the nature of the various subgroups of brain tumors, and the implications of changes in the half-lives as well as the proportions of the subgroups with time are discussed."}
{"id": "PMID:196584", "title": "Abrupt memory loss associated with thalamic tumor.", "content": "We report a case in which glioma with apparent major involvement  of the right thalamus was manifested initially solely by abrupt onset of severe impairment of both recent and moderately remote memory. Distracting stimuli plays a role in prevention of consolidation of memory.", "contents": "Abrupt memory loss associated with thalamic tumor. We report a case in which glioma with apparent major involvement  of the right thalamus was manifested initially solely by abrupt onset of severe impairment of both recent and moderately remote memory. Distracting stimuli plays a role in prevention of consolidation of memory."}
{"id": "PMID:196585", "title": "Perinatal plasma lipid concentrations.", "content": "The effect of the maternal environment on umbilical cord plasma lipid concentrations was studied in a group of mothers and babies. Changes in neonatal plasma concentrations during the first week of life were followed in a small group of infants. The lipoprotein distribution of the cholesterol and triglyceride content of umbilical cord plasma was similar to that seen in maternal plasma at delivery. Neonatal plasma cholesterol was significantly correlated with the cholesterol content of maternal low density lipoprotein. Neonatal plasma triglyceride concentration was related to maternal parity, duration of labour and the existence of maternal hypertension and to the occurrence of foetal distress and dysmaturity.", "contents": "Perinatal plasma lipid concentrations. The effect of the maternal environment on umbilical cord plasma lipid concentrations was studied in a group of mothers and babies. Changes in neonatal plasma concentrations during the first week of life were followed in a small group of infants. The lipoprotein distribution of the cholesterol and triglyceride content of umbilical cord plasma was similar to that seen in maternal plasma at delivery. Neonatal plasma cholesterol was significantly correlated with the cholesterol content of maternal low density lipoprotein. Neonatal plasma triglyceride concentration was related to maternal parity, duration of labour and the existence of maternal hypertension and to the occurrence of foetal distress and dysmaturity."}
{"id": "PMID:196586", "title": "Arousal from sleep: the physiological and subjective effects of a 15 dB(A) reduction in aircraft flyover noise.", "content": "The present research was concerned with whether or not a 15 dB(A) reduction in overall noise level would lessen the sleep disturbing properties of jet aircraft flyover noise and, if less disturbing, whether this would be subjectively appreciated by the sleeping individual. The results indicate that a reduction of 15 dB(A) does result in less sleep disruption but only during sleep characterized by fast-wave electroencephalographic activity. During sleep characterized by slow-wave electroencephalographic activity, such a reduction in the sleep-disturbing properties of jet aircraft noise has little effect. Moreover, even when effective during fast-wave sleep, the decreased arousal produced by the lower noise levels is not subjectively appreciated by the individual in terms of his estimate of the quality of his night's sleep. Thus, reducing the overall noise level of jet aircraft flyovers by some 15 dB(A), is, at best, minimally beneficial to sleep.", "contents": "Arousal from sleep: the physiological and subjective effects of a 15 dB(A) reduction in aircraft flyover noise. The present research was concerned with whether or not a 15 dB(A) reduction in overall noise level would lessen the sleep disturbing properties of jet aircraft flyover noise and, if less disturbing, whether this would be subjectively appreciated by the sleeping individual. The results indicate that a reduction of 15 dB(A) does result in less sleep disruption but only during sleep characterized by fast-wave electroencephalographic activity. During sleep characterized by slow-wave electroencephalographic activity, such a reduction in the sleep-disturbing properties of jet aircraft noise has little effect. Moreover, even when effective during fast-wave sleep, the decreased arousal produced by the lower noise levels is not subjectively appreciated by the individual in terms of his estimate of the quality of his night's sleep. Thus, reducing the overall noise level of jet aircraft flyovers by some 15 dB(A), is, at best, minimally beneficial to sleep."}
{"id": "PMID:196588", "title": "Systems simulation: theory of monosynaptic transfer between neuron populations.", "content": "This paper presents a theory for the input-output transformation involved in diffuse monosynaptic activation in a neural tissue or organ system of one population of neurons by another. Main findings are: (1) highly diffuse monosynaptic linkages act very much like filters, selectively sensitive to synchronized clusters of action potentials among the fibers of the input population; (2) partially diffuse monosynaptic linkages are capable of effecting either an amplification or diminution of the number of pulses involved in a single synchronized cluster, depending on parameters of the system; and (3) partially diffuse and spatially organized monosynaptic linkages are capable of effecting a spatial inversion of fine-grained spatial patterns. Theoretical predictions are clarified by mathematical analysis and computer simulation.", "contents": "Systems simulation: theory of monosynaptic transfer between neuron populations. This paper presents a theory for the input-output transformation involved in diffuse monosynaptic activation in a neural tissue or organ system of one population of neurons by another. Main findings are: (1) highly diffuse monosynaptic linkages act very much like filters, selectively sensitive to synchronized clusters of action potentials among the fibers of the input population; (2) partially diffuse monosynaptic linkages are capable of effecting either an amplification or diminution of the number of pulses involved in a single synchronized cluster, depending on parameters of the system; and (3) partially diffuse and spatially organized monosynaptic linkages are capable of effecting a spatial inversion of fine-grained spatial patterns. Theoretical predictions are clarified by mathematical analysis and computer simulation."}
{"id": "PMID:196589", "title": "Diabetes and the control of pyruvate dehydrogenase in rat heart mitochondria by concentration ratios of adenosine triphosphate/adenosine diphosphate, of reduced/oxidized nicotinamide-adenine dinucleotide and of acetyl-coenzyme A/coenzyme A.", "content": "1. The proportion of active (dephosphorylated) pyruvate dehydrogenase in rat heart mitochondria was correlated with total concentration ratios of ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA. These metabolites were measured with ATP-dependent and NADH-dependent luciferases. 2. Increase in the concentration ratio of NADH/NAD+ at constant [ATP]/[ADP] and [acetyl-CoA]/[CoA] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between mitochondria incubated with 0.4mM- or 1mM-succinate and mitochondria incubated with 0.4mM-succinate+/-rotenone. 3. Increase in the concentration ratio acetyl-CoA/CoA at constant [ATP]/[ADP] and [NADH][NAD+] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between incubations in 50 micrometer-palmitotoyl-L-carnitine and in 250 micrometer-2-oxoglutarate +50 micrometer-L-malate. 4. These findings are consistent with activation of the pyruvate dehydrogenase kinase reaction by high ratios of [NADH]/[NAD+] and of [acetyl-CoA]/[CoA]. 5. Comparison between mitochondria from hearts of diabetic and non-diabetic rats shows that phosphorylation and inactivation of pyruvate dehydrogenase is enhanced in alloxan-diabetes by some factor other than concentration ratios of ATP/ADP, NADH/NAD+ or acetyl-CoA/CoA.", "contents": "Diabetes and the control of pyruvate dehydrogenase in rat heart mitochondria by concentration ratios of adenosine triphosphate/adenosine diphosphate, of reduced/oxidized nicotinamide-adenine dinucleotide and of acetyl-coenzyme A/coenzyme A. 1. The proportion of active (dephosphorylated) pyruvate dehydrogenase in rat heart mitochondria was correlated with total concentration ratios of ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA. These metabolites were measured with ATP-dependent and NADH-dependent luciferases. 2. Increase in the concentration ratio of NADH/NAD+ at constant [ATP]/[ADP] and [acetyl-CoA]/[CoA] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between mitochondria incubated with 0.4mM- or 1mM-succinate and mitochondria incubated with 0.4mM-succinate+/-rotenone. 3. Increase in the concentration ratio acetyl-CoA/CoA at constant [ATP]/[ADP] and [NADH][NAD+] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between incubations in 50 micrometer-palmitotoyl-L-carnitine and in 250 micrometer-2-oxoglutarate +50 micrometer-L-malate. 4. These findings are consistent with activation of the pyruvate dehydrogenase kinase reaction by high ratios of [NADH]/[NAD+] and of [acetyl-CoA]/[CoA]. 5. Comparison between mitochondria from hearts of diabetic and non-diabetic rats shows that phosphorylation and inactivation of pyruvate dehydrogenase is enhanced in alloxan-diabetes by some factor other than concentration ratios of ATP/ADP, NADH/NAD+ or acetyl-CoA/CoA."}
{"id": "PMID:196590", "title": "Effect of cortisol acetate on collagen biosynthesis and on the activities of prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase and collagen glucosyltransferase in chick-embryo tendon cells.", "content": "Collagen synthesis and the activities of prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase and collagen glucosyltransferase were studied in isolated chick-embryo tendon cells after the administration of cortisol acetate to the chick embryos. When the steroid was injected 1 day before isolation of the tendon cells, collagen synthesis was decreased, even though the enzyme activities were not changed. When cortisol acetate was given as repeated injections over a period of 4 days, both collagen synthesis and the enzyme activities decreased. The hydroxylase activities decreased even more than the two collagen glycosyltransferase activities, both in isolated cells and in whole chick embryos. The amount of prolyl hydroxylase protein diminished to the same extent as the enzyme activity, indicating that cortisol acetate inhibits enzyme synthesis. The inhibitory effect of cortisol acetate on collagen synthesis and on the enzyme activities was partially reversible in 3 days. Total protein synthesis was completely restored within this time. Only massive doses of cortisol acetate inhibited collagen synthesis in vitro. Additional experiments indicated that cortisol acetate did not decrease the rate of the enzyme reactions when added directly to the enzyme incubation mixtures. The results suggest that cortisol acetate decreases collagen synthesis both by its direct effect on collagen polypeptide-chain synthesis and by decreasing the activities of enzymes involved in post-translational modifications.", "contents": "Effect of cortisol acetate on collagen biosynthesis and on the activities of prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase and collagen glucosyltransferase in chick-embryo tendon cells. Collagen synthesis and the activities of prolyl hydroxylase, lysyl hydroxylase, collagen galactosyltransferase and collagen glucosyltransferase were studied in isolated chick-embryo tendon cells after the administration of cortisol acetate to the chick embryos. When the steroid was injected 1 day before isolation of the tendon cells, collagen synthesis was decreased, even though the enzyme activities were not changed. When cortisol acetate was given as repeated injections over a period of 4 days, both collagen synthesis and the enzyme activities decreased. The hydroxylase activities decreased even more than the two collagen glycosyltransferase activities, both in isolated cells and in whole chick embryos. The amount of prolyl hydroxylase protein diminished to the same extent as the enzyme activity, indicating that cortisol acetate inhibits enzyme synthesis. The inhibitory effect of cortisol acetate on collagen synthesis and on the enzyme activities was partially reversible in 3 days. Total protein synthesis was completely restored within this time. Only massive doses of cortisol acetate inhibited collagen synthesis in vitro. Additional experiments indicated that cortisol acetate did not decrease the rate of the enzyme reactions when added directly to the enzyme incubation mixtures. The results suggest that cortisol acetate decreases collagen synthesis both by its direct effect on collagen polypeptide-chain synthesis and by decreasing the activities of enzymes involved in post-translational modifications."}
{"id": "PMID:196591", "title": "The probable site of action of thenolytrifluoracetone on the respiratory chain.", "content": "1. It is shown that the electron-transfer inhibitor thenoyltrifluoroacetone abolishes a respiratory-chain electron-paramagnetic-resonance absorbance due to spin-spin interactions of ubisemiquinones at concentrations similar to those required for inhibition of succinate oxidation. 2. A specific site of interaction of thenoyltrifluoroacetone with the respiratory chain is proposed to be on the ubisemiquinone with which succinate dehydrogenase reacts. 3. Our results further demonstrate the close association of the HiPIP (high-potential iron-sulphur) centre of succinate dehydrogenase with ubisemiquinone.", "contents": "The probable site of action of thenolytrifluoracetone on the respiratory chain. 1. It is shown that the electron-transfer inhibitor thenoyltrifluoroacetone abolishes a respiratory-chain electron-paramagnetic-resonance absorbance due to spin-spin interactions of ubisemiquinones at concentrations similar to those required for inhibition of succinate oxidation. 2. A specific site of interaction of thenoyltrifluoroacetone with the respiratory chain is proposed to be on the ubisemiquinone with which succinate dehydrogenase reacts. 3. Our results further demonstrate the close association of the HiPIP (high-potential iron-sulphur) centre of succinate dehydrogenase with ubisemiquinone."}
{"id": "PMID:196592", "title": "Cytochrome c-specific protein methylase III from Neurospora crassa.", "content": "A protein methylase III responsible for specifically methylating the cytochrome c in Neurospora crassa was partially characterized by using unmethylated horse heart cytochrome c as a substrate. This enzyme utilizes S-adenosyl-L-methionine as the methyl donor. An analysis of the distribution of [14C]methyl groups in the peptides obtained by chymotrypsin digestion of the enzymically methylated cytochrome c showed that all of the radioactivity could be recovered within a single peak after chromatography. This indicates that the enzyme methylates a specific amino acid sequence within cytochrome c. On hydrolysis of the radioactive chymotryptic peptide, Me-14C-labelled epsilon -N-mono-methyl-lysine, epsilon-N-dimethyl-lysine and epsilon-N-trimethyl-lysine were identified. The enzyme can easily be extracted from the N. crassa mycelial pads and was purified approx. 30-fold.", "contents": "Cytochrome c-specific protein methylase III from Neurospora crassa. A protein methylase III responsible for specifically methylating the cytochrome c in Neurospora crassa was partially characterized by using unmethylated horse heart cytochrome c as a substrate. This enzyme utilizes S-adenosyl-L-methionine as the methyl donor. An analysis of the distribution of [14C]methyl groups in the peptides obtained by chymotrypsin digestion of the enzymically methylated cytochrome c showed that all of the radioactivity could be recovered within a single peak after chromatography. This indicates that the enzyme methylates a specific amino acid sequence within cytochrome c. On hydrolysis of the radioactive chymotryptic peptide, Me-14C-labelled epsilon -N-mono-methyl-lysine, epsilon-N-dimethyl-lysine and epsilon-N-trimethyl-lysine were identified. The enzyme can easily be extracted from the N. crassa mycelial pads and was purified approx. 30-fold."}
{"id": "PMID:196593", "title": "The use of non-aqueous chloroform/methanol extraction for the delipidation of brain with minimal loss of enzyme activities.", "content": "When freeze-dried brain was extracted at -4-0degrees C with dry chloroform/methanol (2:1 v/v), four of the five enzymes examined were recovered in the diethyl ether-washed residue without inactivation. By contrast, extraction with chloroform/methanol (2:1 v/v) in the presence of water destroyed activities of all the enzymes examined. The amounts of major lipids extracted were similar whether extraction was done in the absence or presence of water. The study was carried out with special interest in 2':3'-cyclic nucleotide 3'-phosphodiesterase (EC 3.1.4.37), which is firmly bound to the membrane structures of brain white matter.", "contents": "The use of non-aqueous chloroform/methanol extraction for the delipidation of brain with minimal loss of enzyme activities. When freeze-dried brain was extracted at -4-0degrees C with dry chloroform/methanol (2:1 v/v), four of the five enzymes examined were recovered in the diethyl ether-washed residue without inactivation. By contrast, extraction with chloroform/methanol (2:1 v/v) in the presence of water destroyed activities of all the enzymes examined. The amounts of major lipids extracted were similar whether extraction was done in the absence or presence of water. The study was carried out with special interest in 2':3'-cyclic nucleotide 3'-phosphodiesterase (EC 3.1.4.37), which is firmly bound to the membrane structures of brain white matter."}
{"id": "PMID:196594", "title": "The synthesis of tritium-labelled human corticotropin of high specific radioactivity.", "content": "Human [[3,5-3H2]Tyr23]corticotropin-(1-39)-nonatriacontapeptide of specific radioactivity 25.2 Ci/mmol, identical with unlabelled human corticotropin by several criteria, was prepared via the fully protected di-iodotyrosine compound. The latter was synthesized by classical procedures.", "contents": "The synthesis of tritium-labelled human corticotropin of high specific radioactivity. Human [[3,5-3H2]Tyr23]corticotropin-(1-39)-nonatriacontapeptide of specific radioactivity 25.2 Ci/mmol, identical with unlabelled human corticotropin by several criteria, was prepared via the fully protected di-iodotyrosine compound. The latter was synthesized by classical procedures."}
{"id": "PMID:196595", "title": "Adenosine 3':5'-cyclic monophosphate in higher plants: Isolation and characterization of adenosine 3':5'-cyclic monophosphate from Kalanchoe and Agave.", "content": "1.3':5'-Cyclic AMP was extensively purified from Kalanchoe daigremontiana and Agave americana by neutral alumina and anion- and cation-exchange column chromatography. Inclusion of 3':5'-cyclic [8-3H]AMP from the point of tissue extraction permitted calculation of yields. The purification procedure removed contaminating material that was shown to interfere with the 3':5'-cyclic AMP estimation and characterization procedures. 2. The partially purified 3':5'-cyclic AMP was quantified by means of a radiochemical saturation assay using an ox heart 3':5'-cyclic AMP-binding protein and by an assay involving activation of a mammalian protein kinase. 3. The plant 3':5'-cyclic AMP co-migrated with 3':5'-cyclic [8-3H]AMP on cellulose chromatography, poly(ethyleneimine)-cellulose chromatography and silica-gel t.l.c. developed with several solvent systems. 4. The plant 3':5'-cyclic AMP was degraded by ox heart 3':5'-cyclic nucleotide phosphodiesterase at the same rates as authentic 3':5'-cyclic AMP. 1-Methyl-3-isobutylxanthine (1 mM), a specific inhibitor of the 3':5'-cyclic nucleotide phosphodieterase, completely inhibited such degradation. 5. The concentrations of 3':5'-cyclic AMP satisfying the above criteria in Kalanchoe and Agave were 2-6 and 1 pmol/g fresh wt. respectively. Possible bacterial contribution to these analyses was estimated to be less than 0.002pmol/g fresh wt. Evidence for the occurrence of 3':5'-cyclic AMP in plants is discussed.", "contents": "Adenosine 3':5'-cyclic monophosphate in higher plants: Isolation and characterization of adenosine 3':5'-cyclic monophosphate from Kalanchoe and Agave. 1.3':5'-Cyclic AMP was extensively purified from Kalanchoe daigremontiana and Agave americana by neutral alumina and anion- and cation-exchange column chromatography. Inclusion of 3':5'-cyclic [8-3H]AMP from the point of tissue extraction permitted calculation of yields. The purification procedure removed contaminating material that was shown to interfere with the 3':5'-cyclic AMP estimation and characterization procedures. 2. The partially purified 3':5'-cyclic AMP was quantified by means of a radiochemical saturation assay using an ox heart 3':5'-cyclic AMP-binding protein and by an assay involving activation of a mammalian protein kinase. 3. The plant 3':5'-cyclic AMP co-migrated with 3':5'-cyclic [8-3H]AMP on cellulose chromatography, poly(ethyleneimine)-cellulose chromatography and silica-gel t.l.c. developed with several solvent systems. 4. The plant 3':5'-cyclic AMP was degraded by ox heart 3':5'-cyclic nucleotide phosphodiesterase at the same rates as authentic 3':5'-cyclic AMP. 1-Methyl-3-isobutylxanthine (1 mM), a specific inhibitor of the 3':5'-cyclic nucleotide phosphodieterase, completely inhibited such degradation. 5. The concentrations of 3':5'-cyclic AMP satisfying the above criteria in Kalanchoe and Agave were 2-6 and 1 pmol/g fresh wt. respectively. Possible bacterial contribution to these analyses was estimated to be less than 0.002pmol/g fresh wt. Evidence for the occurrence of 3':5'-cyclic AMP in plants is discussed."}
{"id": "PMID:196603", "title": "[Trigeminal herpes zoster].", "content": "The authors, after a brief discussion about etiopathogenesis, istopathological changes and principal symptomatologic and therapeutic elements of Herpes Zoster, present three  personal observations of Herpes Zoster facialis, two affecting only the third branch of the trigeminus nerve and one only its second branch. Finally they discuss, basing on clinical peculiarities, a possible diagnostic localization of the disease.", "contents": "[Trigeminal herpes zoster]. The authors, after a brief discussion about etiopathogenesis, istopathological changes and principal symptomatologic and therapeutic elements of Herpes Zoster, present three  personal observations of Herpes Zoster facialis, two affecting only the third branch of the trigeminus nerve and one only its second branch. Finally they discuss, basing on clinical peculiarities, a possible diagnostic localization of the disease."}
{"id": "PMID:196609", "title": "Tracheal cylindroma: anaesthetic management.", "content": "A tracheal cylindroma in a lady aged 56 yr was excised. The problems of tracheal and carinal resection, and an anaesthetic technique which obviates the use of cardiopulmonary bypass are described.", "contents": "Tracheal cylindroma: anaesthetic management. A tracheal cylindroma in a lady aged 56 yr was excised. The problems of tracheal and carinal resection, and an anaesthetic technique which obviates the use of cardiopulmonary bypass are described."}
{"id": "PMID:196610", "title": "Sulphated acid mucopolysaccharides in SV40-transformed human cells from normal and mucopolysaccharidosis patients.", "content": "Lines of fibroblasts have been established from normal individuals and from patients diagnosed as suffering from one of the mucopolysaccharidoses or mucopolysaccharide-storage diseases. Transformation of these lines with SV40 virus has been found to reduce their capacity to secrete sulphated mucopolysaccharides into the growth medium. No differences were detected between the individual cell types in their secretory capacity, either before or after viral transformation. A direct relationship was found to exist between the rate of acid mucopolysaccharide production and cell-doubling time. The level of sulphated mucopolysaccharide detected within the cell was also reduced for all cell types after transformation by SV40. Transformed fibroblasts from mucopolysaccharidosis patients, however, showed a relatively greater reduction in storage capacity than those derived from normal individuals.", "contents": "Sulphated acid mucopolysaccharides in SV40-transformed human cells from normal and mucopolysaccharidosis patients. Lines of fibroblasts have been established from normal individuals and from patients diagnosed as suffering from one of the mucopolysaccharidoses or mucopolysaccharide-storage diseases. Transformation of these lines with SV40 virus has been found to reduce their capacity to secrete sulphated mucopolysaccharides into the growth medium. No differences were detected between the individual cell types in their secretory capacity, either before or after viral transformation. A direct relationship was found to exist between the rate of acid mucopolysaccharide production and cell-doubling time. The level of sulphated mucopolysaccharide detected within the cell was also reduced for all cell types after transformation by SV40. Transformed fibroblasts from mucopolysaccharidosis patients, however, showed a relatively greater reduction in storage capacity than those derived from normal individuals."}
{"id": "PMID:196611", "title": "Bilateral spontaneous pneumothorax with pulmonary metastases from synovial cell sarcoma.", "content": "The association of bilateral spontaneous pneumothroax with pulmonary metastases is rare. The clinical and radiological features of bilateral spontaneous pneumothorax with pulmonary metastases from a synovial cell sarcoma are described in a 16-year-old Punjabi student.", "contents": "Bilateral spontaneous pneumothorax with pulmonary metastases from synovial cell sarcoma. The association of bilateral spontaneous pneumothroax with pulmonary metastases is rare. The clinical and radiological features of bilateral spontaneous pneumothorax with pulmonary metastases from a synovial cell sarcoma are described in a 16-year-old Punjabi student."}
{"id": "PMID:196612", "title": "Lymphocyte abnormalities in myeloma.", "content": "Lymphopenia and monocytosis were found in one third of untreated myeloma patients but there was no correlation between the two. Half of the patients studied had an increase in medium basophilic lymphoid cells, and eight had a raised PAS score. Lymphocytes from the majority of untreated myeloma patients failed to respond to antigenic stimulation in vitro compared with age matched controls. Three patients were immunized but showed no increase in immunoblasts or rise in antibody titre. The findings strongly suggest that abnormal lymphocytes are present in the blood in myeloma. The failure of lymphocytes to respond to antigen provides an explanation for the lack of normal plasma cells and depressed antibody responses in myeloma.", "contents": "Lymphocyte abnormalities in myeloma. Lymphopenia and monocytosis were found in one third of untreated myeloma patients but there was no correlation between the two. Half of the patients studied had an increase in medium basophilic lymphoid cells, and eight had a raised PAS score. Lymphocytes from the majority of untreated myeloma patients failed to respond to antigenic stimulation in vitro compared with age matched controls. Three patients were immunized but showed no increase in immunoblasts or rise in antibody titre. The findings strongly suggest that abnormal lymphocytes are present in the blood in myeloma. The failure of lymphocytes to respond to antigen provides an explanation for the lack of normal plasma cells and depressed antibody responses in myeloma."}
{"id": "PMID:196613", "title": "Antibody activity to type 1 and type 2 herpes simplex virus in human cervical mucus.", "content": "Neutralizing antibody activity in cervical mucus to type 1 herpes virus was detected in 24 of 28 patients, and to type 2 herpes simplex virus in 18 of 24 patients. The neutralizing antibody activity resisted heat inactivation for 30 minutes at 56 degrees C, was independent of complement and followed first order kinetics. There was evidence of antibody against both virus types in immunoglobulin fractions IgG and IgA, the latter containing approximately threefold greater neutralizing antibody activity per unit of immunoglobulin concentration. Type 1 and type 2 neutralizing antibody activity showed a positive but weak correlation and type 2 neutralizing antibody activity showed a positive but weak correlation and a type-common immunoprecipitin was identified in all concentrated pooled mucus samples. However, type-specific neutralizing antibody against both virus types was identified in pooled mucus samples by heterologous absorption techniques. There was a relatively higher average type 2 neutralizing antibody activity in the mucus than in the serum and there was no correlation between serum and mucus antibody levels for either virus type. These observations support the concept of an independent local antibody system for herpes simplex virus in the uterine cervix.", "contents": "Antibody activity to type 1 and type 2 herpes simplex virus in human cervical mucus. Neutralizing antibody activity in cervical mucus to type 1 herpes virus was detected in 24 of 28 patients, and to type 2 herpes simplex virus in 18 of 24 patients. The neutralizing antibody activity resisted heat inactivation for 30 minutes at 56 degrees C, was independent of complement and followed first order kinetics. There was evidence of antibody against both virus types in immunoglobulin fractions IgG and IgA, the latter containing approximately threefold greater neutralizing antibody activity per unit of immunoglobulin concentration. Type 1 and type 2 neutralizing antibody activity showed a positive but weak correlation and type 2 neutralizing antibody activity showed a positive but weak correlation and a type-common immunoprecipitin was identified in all concentrated pooled mucus samples. However, type-specific neutralizing antibody against both virus types was identified in pooled mucus samples by heterologous absorption techniques. There was a relatively higher average type 2 neutralizing antibody activity in the mucus than in the serum and there was no correlation between serum and mucus antibody levels for either virus type. These observations support the concept of an independent local antibody system for herpes simplex virus in the uterine cervix."}
{"id": "PMID:196614", "title": "Trophoblastic tumour, oral contraceptive therapy and pregnancy associated alpha2-glycoprotein (PAAG), case report.", "content": "Pregnancy associated alpha2-glycoprotein (PAAG) and human chorionic gonadotrophin (HCG) levels were studied in a patient with an invasive mole who was being treated with cytotoxic drugs and oral contraceptives. Both the PAAG and HCG levels fell during cytotoxic drug treatment while oral contraceptives caused a rise in PAAG concentrations. A relation between oestrogen-induced PAAG and prolonged survival of trophoblastic tumour is proposed.", "contents": "Trophoblastic tumour, oral contraceptive therapy and pregnancy associated alpha2-glycoprotein (PAAG), case report. Pregnancy associated alpha2-glycoprotein (PAAG) and human chorionic gonadotrophin (HCG) levels were studied in a patient with an invasive mole who was being treated with cytotoxic drugs and oral contraceptives. Both the PAAG and HCG levels fell during cytotoxic drug treatment while oral contraceptives caused a rise in PAAG concentrations. A relation between oestrogen-induced PAAG and prolonged survival of trophoblastic tumour is proposed."}
{"id": "PMID:196615", "title": "Effect of dietary protein level on some key enzymes of the tryptophan-NAD pathway.", "content": "1. Six groups of rats were given diets containing protein at three levels (50, 100 and 200 g/kg), with and without nicotinic acid. After 4 weeks on these diets some key enzymes of the tryptophan and nicotinic acid-NAD pathway, liver nicotinamide nucleotide concentration, and urinary metabolites of tryptophan and nicotinic acid were studied. 2. Liver nicotinamide nucleotide levels were lower in rats given the diet with 50 g protein/kg as compared to those in rats given diets with 100 and 200 g protein/kg. The addition of nicotinic acid to the diet resulted in a significant increase in the levels of nicotinamide nucleotides only in rats given 50 g protein/kg diet but not in those given either 100 or 200 g protein/kg diet. 3. Liver tryptophan oxygenase (EC 1.13.1.12) activity increased with increasing dietary protein level. Niconitic acid in the diet had no effect on its activity. 4. Quinolinate phosphoribosyltransferase (EC 2.4.2.a) activity in liver was inversely related to dietary protein level, and nicotinic acid in the diet had no effect on its activity. 5. Liver nicotinate phosphoribosyltransferase (EC 2.4.2.11) activity and kidney picolinate carboxylase (EC 4.1.1.45) activity were not altered either by dietary protein level or nicotinic acid in the diet. 6. The addition of nicotinic acid to the diet resulted in increased excretion of N'-methylnicotinamide at all dietary protein levels. 7. The inverse relationship between protein level in the diet and liver quinolinate phosphoribosyltransferase activity, the rate-limiting enzyme of the tryptophan-NAD pathway suggests that the efficiency of conversion of tryptophan to NAD is related to protein level in the diet, the efficiency decreasing with an increase in the level of dietary protein.", "contents": "Effect of dietary protein level on some key enzymes of the tryptophan-NAD pathway. 1. Six groups of rats were given diets containing protein at three levels (50, 100 and 200 g/kg), with and without nicotinic acid. After 4 weeks on these diets some key enzymes of the tryptophan and nicotinic acid-NAD pathway, liver nicotinamide nucleotide concentration, and urinary metabolites of tryptophan and nicotinic acid were studied. 2. Liver nicotinamide nucleotide levels were lower in rats given the diet with 50 g protein/kg as compared to those in rats given diets with 100 and 200 g protein/kg. The addition of nicotinic acid to the diet resulted in a significant increase in the levels of nicotinamide nucleotides only in rats given 50 g protein/kg diet but not in those given either 100 or 200 g protein/kg diet. 3. Liver tryptophan oxygenase (EC 1.13.1.12) activity increased with increasing dietary protein level. Niconitic acid in the diet had no effect on its activity. 4. Quinolinate phosphoribosyltransferase (EC 2.4.2.a) activity in liver was inversely related to dietary protein level, and nicotinic acid in the diet had no effect on its activity. 5. Liver nicotinate phosphoribosyltransferase (EC 2.4.2.11) activity and kidney picolinate carboxylase (EC 4.1.1.45) activity were not altered either by dietary protein level or nicotinic acid in the diet. 6. The addition of nicotinic acid to the diet resulted in increased excretion of N'-methylnicotinamide at all dietary protein levels. 7. The inverse relationship between protein level in the diet and liver quinolinate phosphoribosyltransferase activity, the rate-limiting enzyme of the tryptophan-NAD pathway suggests that the efficiency of conversion of tryptophan to NAD is related to protein level in the diet, the efficiency decreasing with an increase in the level of dietary protein."}
{"id": "PMID:196616", "title": "The effect of dietary calcium on the activity of 25-hydroxycholecalciferol-1-hydroxylase and Ca absorption in vitamin D-replete chicks.", "content": "1. As most of the studies on the regulation of renal 25-hydroxycholecalciferol-1-hydroxylase (25-HCC-1-hydroxylase) activity have been done in marginally-vitamin D-deficient animals and as it is known that vitamin D administration suppresses the specific activity of the 25-HCC-1-hydroxylase, it was decided to study the effect of dietary calcium on the activity of 25-HCC-1-hydroxylase and on Ca absorption in vitamin D-replete chicks. 2. Chicks, 10 d old, were given diets differing in their Ca contents (65 nmol cholecalciferol/kg diet) for 10 d and the activity of 25-HCC-1-hydroxylase in kidney homogenates, Ca absorption from the duodenum, Ca-binding protein (CaBP) activity in the duodenal mucosa and plasma Ca and phosphate concentrations were all determined. 3. The CaBP activity and the efficiency of Ca absorption both decreased with increasing dietary intake of Ca. Ca absorption and CaBP activity were significantly correlated (r 0-995, P less than 0-01). 4. The activity of 25-HCC-1-hydroxylase decreased as the dietary level of Ca increased and was significantly correlated with Ca absorption (r 0-900, P less than 0-05). The plasma Ca concentration and the activity of 25-HCC-1-hydroxylase were inversely related (r-0-940, P less than 0-01). 5. It is concluded that in the vitamin D-replete chick the efficiency of duodenal Ca absorption is regulated by the renal 25-HCC-1-hydroxylase activity via production of 1,25-dihydroxycholecalciferol and CaBP synthesis.", "contents": "The effect of dietary calcium on the activity of 25-hydroxycholecalciferol-1-hydroxylase and Ca absorption in vitamin D-replete chicks. 1. As most of the studies on the regulation of renal 25-hydroxycholecalciferol-1-hydroxylase (25-HCC-1-hydroxylase) activity have been done in marginally-vitamin D-deficient animals and as it is known that vitamin D administration suppresses the specific activity of the 25-HCC-1-hydroxylase, it was decided to study the effect of dietary calcium on the activity of 25-HCC-1-hydroxylase and on Ca absorption in vitamin D-replete chicks. 2. Chicks, 10 d old, were given diets differing in their Ca contents (65 nmol cholecalciferol/kg diet) for 10 d and the activity of 25-HCC-1-hydroxylase in kidney homogenates, Ca absorption from the duodenum, Ca-binding protein (CaBP) activity in the duodenal mucosa and plasma Ca and phosphate concentrations were all determined. 3. The CaBP activity and the efficiency of Ca absorption both decreased with increasing dietary intake of Ca. Ca absorption and CaBP activity were significantly correlated (r 0-995, P less than 0-01). 4. The activity of 25-HCC-1-hydroxylase decreased as the dietary level of Ca increased and was significantly correlated with Ca absorption (r 0-900, P less than 0-05). The plasma Ca concentration and the activity of 25-HCC-1-hydroxylase were inversely related (r-0-940, P less than 0-01). 5. It is concluded that in the vitamin D-replete chick the efficiency of duodenal Ca absorption is regulated by the renal 25-HCC-1-hydroxylase activity via production of 1,25-dihydroxycholecalciferol and CaBP synthesis."}
{"id": "PMID:196617", "title": "Nearest neighbor relationships of the polypeptides in ubiquinone cytochrome c reductase (complex III).", "content": "Ubiquinone cytochrome c reductase (complex III) in detergent dispersion has been cross-linked with two reversible cross-linking agents dithiobissuccinimidylpropionate and dimethyl-3.3'-dithiobispropionimidate and the cross-linked products formed have been analyzed by two-dimensional gel electrophoresis. Under mild reaction conditions, polypeptides I and II, II and VI, I and V, and VI and VII were the most prominent subunit pairs seen. With higher levels of reagent, larger aggregates were produced until an aggregate of apparent molecular weight 310 000 was the dominant band on gels. This is the complex III monomer.", "contents": "Nearest neighbor relationships of the polypeptides in ubiquinone cytochrome c reductase (complex III). Ubiquinone cytochrome c reductase (complex III) in detergent dispersion has been cross-linked with two reversible cross-linking agents dithiobissuccinimidylpropionate and dimethyl-3.3'-dithiobispropionimidate and the cross-linked products formed have been analyzed by two-dimensional gel electrophoresis. Under mild reaction conditions, polypeptides I and II, II and VI, I and V, and VI and VII were the most prominent subunit pairs seen. With higher levels of reagent, larger aggregates were produced until an aggregate of apparent molecular weight 310 000 was the dominant band on gels. This is the complex III monomer."}
{"id": "PMID:196620", "title": "Separation and quantitation of intracellular forms of poliovirus RNA by agarose gel electrophoresis.", "content": "Intracellular poliovirus-specific RNA species can be measured directly by electrophoresis of total cytoplasmic nucleic acids through 1% agarose gels, resulting in the separation of single- and double-stranded forms of poliovirus RNA from each other and from HeLa cell 28S ribosomal RNA. Single-stranded RNA molecules differing by only 15% in length are resolved in this gel system. RNA species can be visualized as fluorescen bands appearing after staining of the gels with ethidium bromide and observation under ultraviolet illumination. The total amount of RNA can be determined by densitometric quantitation of the fluorescent response. In this way, the amount of poliovirus-specific RNA within the cytoplasm of HeLa cells infected for various times has been estimated. At 170-min postinfection, there are 0.67 X 10(5) molecules of single-stranded poliovirus RNA per cell and at 230 min, the amount has increased to 3.7 X 10(5) molecules/cell. Poliovirus double-strnaded RNA reaches a maximum of 0.7 X 10(5) molecules/cell at 330 min after infection.", "contents": "Separation and quantitation of intracellular forms of poliovirus RNA by agarose gel electrophoresis. Intracellular poliovirus-specific RNA species can be measured directly by electrophoresis of total cytoplasmic nucleic acids through 1% agarose gels, resulting in the separation of single- and double-stranded forms of poliovirus RNA from each other and from HeLa cell 28S ribosomal RNA. Single-stranded RNA molecules differing by only 15% in length are resolved in this gel system. RNA species can be visualized as fluorescen bands appearing after staining of the gels with ethidium bromide and observation under ultraviolet illumination. The total amount of RNA can be determined by densitometric quantitation of the fluorescent response. In this way, the amount of poliovirus-specific RNA within the cytoplasm of HeLa cells infected for various times has been estimated. At 170-min postinfection, there are 0.67 X 10(5) molecules of single-stranded poliovirus RNA per cell and at 230 min, the amount has increased to 3.7 X 10(5) molecules/cell. Poliovirus double-strnaded RNA reaches a maximum of 0.7 X 10(5) molecules/cell at 330 min after infection."}
{"id": "PMID:196621", "title": "Linear electric field effect in electron paramagnetic resonance for two bisimidazole--heme complexes, model compounds for B and H hemichromes of hemoglobin and for cytochrome b5.", "content": "Bisimidazole-ferric heme is considered to be the structure at the heme site of cytochrome b5 and two different low spin ferric hemochromes spontaneously formed from ferric hemoglobin. The addition of strong base to bisimidazole-ferric heme in organic solvents alters the optical and magnetic properties of this compound. With the use of the linear electric field effect in the electron paramagnetic resonance, we demonstrate that addition of base does not lead to the exchange of hydroxide anion for ligated imidazole and that the bisimidazole structure is retained. Analysis of optical titrations indicates that 2 equiv of base react reversibly with bisimidazole-ferric heme. It is suggested that the two hemichromes formed from hemoglobin differ in structure from one another by the state of protonation of N-1 in the bound imidazoles.", "contents": "Linear electric field effect in electron paramagnetic resonance for two bisimidazole--heme complexes, model compounds for B and H hemichromes of hemoglobin and for cytochrome b5. Bisimidazole-ferric heme is considered to be the structure at the heme site of cytochrome b5 and two different low spin ferric hemochromes spontaneously formed from ferric hemoglobin. The addition of strong base to bisimidazole-ferric heme in organic solvents alters the optical and magnetic properties of this compound. With the use of the linear electric field effect in the electron paramagnetic resonance, we demonstrate that addition of base does not lead to the exchange of hydroxide anion for ligated imidazole and that the bisimidazole structure is retained. Analysis of optical titrations indicates that 2 equiv of base react reversibly with bisimidazole-ferric heme. It is suggested that the two hemichromes formed from hemoglobin differ in structure from one another by the state of protonation of N-1 in the bound imidazoles."}
{"id": "PMID:196622", "title": "Phosphoglycerate mutase from wheat germ: studies with 18O-labeled substrate, investigations of the phosphatase and phosphoryl transfer activities, and evidence for a phosphoryl-enzyme intermediate.", "content": "From studies using unlabeled phospho-D-glycerate in solutions enriched in H2(18)O, and from experiments involving [18O]phospho-D-glycerate, it is shown that the intramolecular isomerization of 2- and 3-phospho-D-glycerate that is catalyzed by the phosphoglycerate mutase from wheat germ does not involve an intermediate 2,3-cyclic phosphate. It is also shown that phosphoglycerate mutase catalyzes the hydrolysis of the substrate analogues 2-phosphoglycolate, 2-phospho-D-lactate, 3-phosphohydroxypropionate, phosphoenolpyruvate, and phosphohydroxypyruvate. The substrates 3- and 2-phospho-D-glycerate are not hydrolyzed, nor are 2,3-bisphospho-D-glycerate, 2-phospho-L-lactate, 3-phospho-L-glycerate, or sn-glycerol 3-phosphate. Although no exchange of D-[14C]glycerate into phospho-D-glycerate can be detected, the enzyme catalyzes the transfer of the phosphoryl group from \"unnatural\" donors such as 2-phosphoglycolate, to the \"natural\" acceptor, D-glycerate. It is concluded that the intramolecular phosphoryl transfer catalyzed by the wheat germ phosphoglycerate mutase follows a pathway involving a phosphoryl-enzyme intermediate.", "contents": "Phosphoglycerate mutase from wheat germ: studies with 18O-labeled substrate, investigations of the phosphatase and phosphoryl transfer activities, and evidence for a phosphoryl-enzyme intermediate. From studies using unlabeled phospho-D-glycerate in solutions enriched in H2(18)O, and from experiments involving [18O]phospho-D-glycerate, it is shown that the intramolecular isomerization of 2- and 3-phospho-D-glycerate that is catalyzed by the phosphoglycerate mutase from wheat germ does not involve an intermediate 2,3-cyclic phosphate. It is also shown that phosphoglycerate mutase catalyzes the hydrolysis of the substrate analogues 2-phosphoglycolate, 2-phospho-D-lactate, 3-phosphohydroxypropionate, phosphoenolpyruvate, and phosphohydroxypyruvate. The substrates 3- and 2-phospho-D-glycerate are not hydrolyzed, nor are 2,3-bisphospho-D-glycerate, 2-phospho-L-lactate, 3-phospho-L-glycerate, or sn-glycerol 3-phosphate. Although no exchange of D-[14C]glycerate into phospho-D-glycerate can be detected, the enzyme catalyzes the transfer of the phosphoryl group from \"unnatural\" donors such as 2-phosphoglycolate, to the \"natural\" acceptor, D-glycerate. It is concluded that the intramolecular phosphoryl transfer catalyzed by the wheat germ phosphoglycerate mutase follows a pathway involving a phosphoryl-enzyme intermediate."}
{"id": "PMID:196623", "title": "Isolation and properties of the rabbit skeletal muscle protein inhibitor of adenosine 3',5'-monophosphate dependent protein kinases.", "content": "The heat-stable protein inhibitor (Walsh, D. A., et al. (1971), J. Biol. Chem. 246, 1977--1985) of the cyclic adenosine 3',5'-monophosphate dependent protein kinase has been isolated in pure form from rabbit skeletal muscle after a 430 000-fold purification with a 47% yield. The four-step procedure involves sequentially a heat treatment, batchwise anion and cation exchange, and affinity chromatography on protein kinase catalytic subunit covalently coupled to Sepharose 4B. The inhibitor is an acidic protein (pI = 4.24) of molecular weight 11 300. It contains 98 amino acid residues none of which contains sulfur and only 2 (phenylalanine and tyrosine) are aromatic. The NH2-terminus is blocked. The muscle content is ca. 0.6 mg of inhibitor per L of intracellular water. The inhibitor is tightly bound to the catalytic subunit of protein kinase (Ki congruent to 2 X 10(-9) M) and acts competitively with respect to the protein substrates. Protein kinase recognizes a short stretch of the inhibitor sequence, in which arginyl side chains play a crucial role. A study of various competitive inhibitors of the kinase confirms the importance of guanidino groups and hydrophobic side chains in the specific interaction with the substrate binding site.", "contents": "Isolation and properties of the rabbit skeletal muscle protein inhibitor of adenosine 3',5'-monophosphate dependent protein kinases. The heat-stable protein inhibitor (Walsh, D. A., et al. (1971), J. Biol. Chem. 246, 1977--1985) of the cyclic adenosine 3',5'-monophosphate dependent protein kinase has been isolated in pure form from rabbit skeletal muscle after a 430 000-fold purification with a 47% yield. The four-step procedure involves sequentially a heat treatment, batchwise anion and cation exchange, and affinity chromatography on protein kinase catalytic subunit covalently coupled to Sepharose 4B. The inhibitor is an acidic protein (pI = 4.24) of molecular weight 11 300. It contains 98 amino acid residues none of which contains sulfur and only 2 (phenylalanine and tyrosine) are aromatic. The NH2-terminus is blocked. The muscle content is ca. 0.6 mg of inhibitor per L of intracellular water. The inhibitor is tightly bound to the catalytic subunit of protein kinase (Ki congruent to 2 X 10(-9) M) and acts competitively with respect to the protein substrates. Protein kinase recognizes a short stretch of the inhibitor sequence, in which arginyl side chains play a crucial role. A study of various competitive inhibitors of the kinase confirms the importance of guanidino groups and hydrophobic side chains in the specific interaction with the substrate binding site."}
{"id": "PMID:196624", "title": "Model studies for molybdenum enzymes. Reduction of cytochrome c complexes by mu-oxo-bis[oxodihydroxo(L-cysteinato)molybdate(V)].", "content": "The reduction by mu-oxo-bis[oxodihydroxo(L-cysteinato)molybdate(V)] (I) of cytochrome c complexes in which the methionine-80 ligand has been replaced by N3-, CN-, or imidazole has been investigated. The N3- and CN-substituted species are reduced by I in a first-order reaction that appears to proceed via a slow dissociation of N3- or CN-, followed by rapid reduction of native cytochrome c. At low concentrations of I, reduction of the imidazole-cytochrome complex occurs by the same mechanism, while, at higher concentrations of I, direct reduction by I and by a monomeric Mo(V) complex in equilibrium with I appears to occur, although at much lower rates than with native cytochrome c. Potentiometric measurements of E degrees for the cytochrome c complexes with N3- and imidazole indicate the lack of reducibility, or reduction in rate relative to native cytochrome c, is not due to thermodynamic reasons. In the case of the CN- complex, E degrees may be too low for direct reduction by I. The effects on the reduction rates are attributed to a conformational change accompanying the replacement of the methionine-80 ligand, which makes the exposed heme edge less available to attack by outer sphere reductants.", "contents": "Model studies for molybdenum enzymes. Reduction of cytochrome c complexes by mu-oxo-bis[oxodihydroxo(L-cysteinato)molybdate(V)]. The reduction by mu-oxo-bis[oxodihydroxo(L-cysteinato)molybdate(V)] (I) of cytochrome c complexes in which the methionine-80 ligand has been replaced by N3-, CN-, or imidazole has been investigated. The N3- and CN-substituted species are reduced by I in a first-order reaction that appears to proceed via a slow dissociation of N3- or CN-, followed by rapid reduction of native cytochrome c. At low concentrations of I, reduction of the imidazole-cytochrome complex occurs by the same mechanism, while, at higher concentrations of I, direct reduction by I and by a monomeric Mo(V) complex in equilibrium with I appears to occur, although at much lower rates than with native cytochrome c. Potentiometric measurements of E degrees for the cytochrome c complexes with N3- and imidazole indicate the lack of reducibility, or reduction in rate relative to native cytochrome c, is not due to thermodynamic reasons. In the case of the CN- complex, E degrees may be too low for direct reduction by I. The effects on the reduction rates are attributed to a conformational change accompanying the replacement of the methionine-80 ligand, which makes the exposed heme edge less available to attack by outer sphere reductants."}
{"id": "PMID:196625", "title": "Purification and initial rate kinetics of acyl-phosphate-hexose phosphotransferase from Aerobacter aerogenes.", "content": "The enzyme acyl-phosphate-hexose phosphotransferase from Aerobacter aerogenes was purified to electrophoretic homogeneity. The molecular weight of the enzyme as determined on Sephadex gels is 150 000. The enzyme possesses potent phosphotransferase and phosphohydrolase activities. Initial rate kinetics were used to investigate the mechanism of acyl-phosphate-hexose phosphotransferase. These studies, which involved a number of different phosphoryl donors and substrate analogues, suggest that the kinetic mechanism is of the rapid equilibrium random Bi Bi type. A number of other enzymes that exhibit both transferase and hydrolase activities involve obligatory covalent enzyme-substrate intermediates in their mechanisms of action.", "contents": "Purification and initial rate kinetics of acyl-phosphate-hexose phosphotransferase from Aerobacter aerogenes. The enzyme acyl-phosphate-hexose phosphotransferase from Aerobacter aerogenes was purified to electrophoretic homogeneity. The molecular weight of the enzyme as determined on Sephadex gels is 150 000. The enzyme possesses potent phosphotransferase and phosphohydrolase activities. Initial rate kinetics were used to investigate the mechanism of acyl-phosphate-hexose phosphotransferase. These studies, which involved a number of different phosphoryl donors and substrate analogues, suggest that the kinetic mechanism is of the rapid equilibrium random Bi Bi type. A number of other enzymes that exhibit both transferase and hydrolase activities involve obligatory covalent enzyme-substrate intermediates in their mechanisms of action."}
{"id": "PMID:196626", "title": "Phosphatidylcholine exchange between the boundary lipid and bilayer domains in cytochrome oxidase containing membranes.", "content": "A phospholipid spin label, 16-doxylphosphatidylcholine, is employed in a study of lipid--protein interactions in cytochrome oxidase containing membranes. Two methods are used to label the membranous cytochrome oxidase: dispersion in cholate with subsequent detergent removal, and fusion with vesicles of the pure phospholipid label in the absence of detergent. A fraction of the label is immobilized, which is calculated to fall in the range of 0.17--0.21 mg of phospholipid/mg of protein (0.15--0.19 after correction for lipids not extracted by chloroform--methanol). This narrow range of values is independent of methods of labeling, protein isolation, and lipid depletion within experimental error. When labeling by fusion is utilized, the patches of pure phosphatidylcholine spin label diffuse in the plane of the bilayer, become diluted, and demonstrate exchange with bound phospholipid. These observations are evidence that boundary lipid, as reflected by the partitioning of the phosphatidylcholine label, is in equilibrium with adjacent bilayer regions and that it consists of a relatively constant amount of phospholipid associated with the hydrophobic portion of the protein.", "contents": "Phosphatidylcholine exchange between the boundary lipid and bilayer domains in cytochrome oxidase containing membranes. A phospholipid spin label, 16-doxylphosphatidylcholine, is employed in a study of lipid--protein interactions in cytochrome oxidase containing membranes. Two methods are used to label the membranous cytochrome oxidase: dispersion in cholate with subsequent detergent removal, and fusion with vesicles of the pure phospholipid label in the absence of detergent. A fraction of the label is immobilized, which is calculated to fall in the range of 0.17--0.21 mg of phospholipid/mg of protein (0.15--0.19 after correction for lipids not extracted by chloroform--methanol). This narrow range of values is independent of methods of labeling, protein isolation, and lipid depletion within experimental error. When labeling by fusion is utilized, the patches of pure phosphatidylcholine spin label diffuse in the plane of the bilayer, become diluted, and demonstrate exchange with bound phospholipid. These observations are evidence that boundary lipid, as reflected by the partitioning of the phosphatidylcholine label, is in equilibrium with adjacent bilayer regions and that it consists of a relatively constant amount of phospholipid associated with the hydrophobic portion of the protein."}
{"id": "PMID:196627", "title": "Metabolically labeled cell membrane proteins in spontaneously and in SV40 virus transformed mouse fibroblasts.", "content": "A family of mouse fibroblast cell lines in exponential phase of growth were compared in protein constitution of their cell membranes. In preparations from these cells enriched in cell-surface membrane we observed one protein component (apparent molecular weight about 250 000) consistently to be reduced or absent in an SV40 virus transformed cell line, when compared with the normal cell line. No such compositional difference was observed in a spontaneously transformed tumorigenic clonal derivative cell line, or in subclones of such a derivative cell line, with or without SV40 virus infection. However, in metabolic labeling experiments with 14C-labeled mixed amino acids, a consistent decrease also was demonstrated in the biosynthesis of the same protein in the SV40 virus infected subclone, as compared to an uninfected sister subclone, during exponential growth. This specific difference in biosynthesis is apparently related to the presence and functioning of the SV40 gene, and correlates with the ability of these cells to grow in viscous medium, but not with cellular tumorigenicity.", "contents": "Metabolically labeled cell membrane proteins in spontaneously and in SV40 virus transformed mouse fibroblasts. A family of mouse fibroblast cell lines in exponential phase of growth were compared in protein constitution of their cell membranes. In preparations from these cells enriched in cell-surface membrane we observed one protein component (apparent molecular weight about 250 000) consistently to be reduced or absent in an SV40 virus transformed cell line, when compared with the normal cell line. No such compositional difference was observed in a spontaneously transformed tumorigenic clonal derivative cell line, or in subclones of such a derivative cell line, with or without SV40 virus infection. However, in metabolic labeling experiments with 14C-labeled mixed amino acids, a consistent decrease also was demonstrated in the biosynthesis of the same protein in the SV40 virus infected subclone, as compared to an uninfected sister subclone, during exponential growth. This specific difference in biosynthesis is apparently related to the presence and functioning of the SV40 gene, and correlates with the ability of these cells to grow in viscous medium, but not with cellular tumorigenicity."}
{"id": "PMID:196628", "title": "Response of adrenal tumor cells to adrenocorticotropin: site of inhibition by cytochalasin B.", "content": "The ability of cytochalasin B to inhibit the steroidogenic response of mouse adrenal tumor cells (Y-1) to adrenocorticotropin (ACTH) was examined with two aims: to consider the specificity of the inhibitor and to determine at what point(s) in the steroidogenic pathway it acts. Cytochalasin B did not inhibit protein synthesis or transport of [3H]-cholesterol into the cells nor did it alter total cell concentration of ATP. Together with previous evidence, this suggests that the effects of cytochalasin observed are relatively specific in these cells. Cytochalasin inhibits the increase in conversion of [3H]cholesterol to 20alpha-[3H]dihydroprogesterone (20alpha-hydroxypregn-4-en-3-one: a major product of the steroid pathway in Y-1 cells) produced by ACTH but does not inhibit conversion of cholesterol to pregnenolone by mitochondrial and purified enzyme preparations from Y-1 cells and bovine adrenal, respectively. Cytochalasin does not inhibit the conversion of pregnenolone to 20alpha-dihydroprogesterone but was shown to inhibit increased transport of [3H]cholesterol to mitochondria resulting from the action of ACTH. These findings indicate that cytochalasin acts after cholesterol has entered the cells and before it is subjected to side-chain cleavage in mitochondria. In view of the known action of cytochalasin on microfilaments, it is proposed that these organelles are necessary for the transport of cholesterol to the mitochondrial cleavage enzyme and that at least one effect of ACTH (and cyclic AMP) is exerted upon this transport process. The specificity of the effects of cytochalasin is considered in relation to this conclusion.", "contents": "Response of adrenal tumor cells to adrenocorticotropin: site of inhibition by cytochalasin B. The ability of cytochalasin B to inhibit the steroidogenic response of mouse adrenal tumor cells (Y-1) to adrenocorticotropin (ACTH) was examined with two aims: to consider the specificity of the inhibitor and to determine at what point(s) in the steroidogenic pathway it acts. Cytochalasin B did not inhibit protein synthesis or transport of [3H]-cholesterol into the cells nor did it alter total cell concentration of ATP. Together with previous evidence, this suggests that the effects of cytochalasin observed are relatively specific in these cells. Cytochalasin inhibits the increase in conversion of [3H]cholesterol to 20alpha-[3H]dihydroprogesterone (20alpha-hydroxypregn-4-en-3-one: a major product of the steroid pathway in Y-1 cells) produced by ACTH but does not inhibit conversion of cholesterol to pregnenolone by mitochondrial and purified enzyme preparations from Y-1 cells and bovine adrenal, respectively. Cytochalasin does not inhibit the conversion of pregnenolone to 20alpha-dihydroprogesterone but was shown to inhibit increased transport of [3H]cholesterol to mitochondria resulting from the action of ACTH. These findings indicate that cytochalasin acts after cholesterol has entered the cells and before it is subjected to side-chain cleavage in mitochondria. In view of the known action of cytochalasin on microfilaments, it is proposed that these organelles are necessary for the transport of cholesterol to the mitochondrial cleavage enzyme and that at least one effect of ACTH (and cyclic AMP) is exerted upon this transport process. The specificity of the effects of cytochalasin is considered in relation to this conclusion."}
{"id": "PMID:196629", "title": "Studies on the 5' termini of Novikoff ascites hepatoma ribosomal precursor RNA.", "content": "The 5' termini of 18S and 28S rRNA and their 32S, 41S, and 45S nRNA precursors were analyzed by fractionating alkaline hydrolysates of the RNAs on columns of diethylaminoethyl-Sephadex A-25 at neutral pH followed by electrophoresis on Whatman 3MM paper at pH 3.5. The results indicate that each RNA begins with a mononucleoside diphosphate of heterogeneous composition. The principal nucleoside diphosphate was pCp in 28S, 32S, 41S, and 45S RNA and pUp in 18S RNA. The 18S rRNA also contained the most homogeneous composition with approximately 70% of the molecules beginning with pUp; the 41S and 45S nRNA termini were the most heterogeneous, each containing pCp in only one-third of the molecules. Each terminal composition was reproducible and characteristic for its RNA. The composition of 28S rRNA was very similar to that of 32S nRNA, but distinctly different from 5.8S or 18S rRNA or 45S nRNA. The isomeric forms of 45S nRNA contained no appreciable amounts of a terminal 5'-triphosphate, although they had similar nucleoside diphosphate compositions. These results are discussed in relation to the transcription of ribosomal genes and the arrangement of the 5.8S rRNA sequence within these genes.", "contents": "Studies on the 5' termini of Novikoff ascites hepatoma ribosomal precursor RNA. The 5' termini of 18S and 28S rRNA and their 32S, 41S, and 45S nRNA precursors were analyzed by fractionating alkaline hydrolysates of the RNAs on columns of diethylaminoethyl-Sephadex A-25 at neutral pH followed by electrophoresis on Whatman 3MM paper at pH 3.5. The results indicate that each RNA begins with a mononucleoside diphosphate of heterogeneous composition. The principal nucleoside diphosphate was pCp in 28S, 32S, 41S, and 45S RNA and pUp in 18S RNA. The 18S rRNA also contained the most homogeneous composition with approximately 70% of the molecules beginning with pUp; the 41S and 45S nRNA termini were the most heterogeneous, each containing pCp in only one-third of the molecules. Each terminal composition was reproducible and characteristic for its RNA. The composition of 28S rRNA was very similar to that of 32S nRNA, but distinctly different from 5.8S or 18S rRNA or 45S nRNA. The isomeric forms of 45S nRNA contained no appreciable amounts of a terminal 5'-triphosphate, although they had similar nucleoside diphosphate compositions. These results are discussed in relation to the transcription of ribosomal genes and the arrangement of the 5.8S rRNA sequence within these genes."}
{"id": "PMID:196631", "title": "Comparative study of hen yolk phosvitin and plasma vitellogenin.", "content": "Vitellogenin, the only phosphoprotein detectable in the plasma of laying hens, is present at an approximate concentration of 1 mg/mL and can be isolated by chromatography on diethylaminoethylcellulose. Vitellogenin has a molecular weight of 235 000--240 000 and contains approximately 3% phosphorus by weight. Evidence that this protein is the precursor of phosvitins includes its ability to act as an acceptor for phosphate with a phosvitin specific kinase, the generation of a peptide similar to phosvitin by trypsinization, and the presence of distinctive peptides of multiple clustered phosphoserine upon partial acid hydrolysis. This partial sequence similarity between phosvitins and vitellogenin has not been previously reported. The phosphorus content and amino acid composition of vitellogenin are consistent with a model which contains two phosvitins and one lipovitellin. The total molecular weights of these proteins (28 000 + 34 000 + 170 000 = 232 000) are close to that of vitellogenin.", "contents": "Comparative study of hen yolk phosvitin and plasma vitellogenin. Vitellogenin, the only phosphoprotein detectable in the plasma of laying hens, is present at an approximate concentration of 1 mg/mL and can be isolated by chromatography on diethylaminoethylcellulose. Vitellogenin has a molecular weight of 235 000--240 000 and contains approximately 3% phosphorus by weight. Evidence that this protein is the precursor of phosvitins includes its ability to act as an acceptor for phosphate with a phosvitin specific kinase, the generation of a peptide similar to phosvitin by trypsinization, and the presence of distinctive peptides of multiple clustered phosphoserine upon partial acid hydrolysis. This partial sequence similarity between phosvitins and vitellogenin has not been previously reported. The phosphorus content and amino acid composition of vitellogenin are consistent with a model which contains two phosvitins and one lipovitellin. The total molecular weights of these proteins (28 000 + 34 000 + 170 000 = 232 000) are close to that of vitellogenin."}
{"id": "PMID:196634", "title": "Redetermination of the pressure dependence of the lipid bilayer phase transition.", "content": "The effect of pressure on the phase transition temperature for the dipalmitoyllecithin bilayer was redetermined by following the volume change accompanying the transition. These measurements were carried out isothermally with the transition from the ordered to the disordered phase induced by decreasing the pressure. This contrasts with our previous measurements which were carried out at constant pressure and increasing temperature. The transition at every temperature was sharp and confirmed our previous observation that the volume change associated with the transition (0.033 mL g-1) is invariant with pressure. However, our present measurements, in contrast to our previous results, indicate that dP m/dTm at all pressures is in agreement with the 1 atm value of delta H/Tm delta V within experimental error where Tm and Pm are the temperature and pressure of the phase transition, respectively. These results, which are now in agreement with all other known pressure data, indicate that the entropy change associated with the transition is invariant with pressure.", "contents": "Redetermination of the pressure dependence of the lipid bilayer phase transition. The effect of pressure on the phase transition temperature for the dipalmitoyllecithin bilayer was redetermined by following the volume change accompanying the transition. These measurements were carried out isothermally with the transition from the ordered to the disordered phase induced by decreasing the pressure. This contrasts with our previous measurements which were carried out at constant pressure and increasing temperature. The transition at every temperature was sharp and confirmed our previous observation that the volume change associated with the transition (0.033 mL g-1) is invariant with pressure. However, our present measurements, in contrast to our previous results, indicate that dP m/dTm at all pressures is in agreement with the 1 atm value of delta H/Tm delta V within experimental error where Tm and Pm are the temperature and pressure of the phase transition, respectively. These results, which are now in agreement with all other known pressure data, indicate that the entropy change associated with the transition is invariant with pressure."}
{"id": "PMID:196635", "title": "Phospholipid-protein interactions in human low density lipoprotein detected by 31P nuclear magnetic resonance.", "content": "31P nuclear magnetic resonance (NMR) spectra of human low density lipoprotein (LDL) has been obtained and the major phospholipid components identified. Analysis of the spectra revealed two phospholipid environments: one occupied by 4/5 of the phospholipid with high resolution resonances possessing properties similar to phospholipids in vesicles, and a second occupied by 1/5 of the phospholipid with broad lines indicative of immobilization. Limited trypsin treatment of the particle cleaved all of the B peptide into smaller molecular weight peptides which remained with the particle. Trypsin-treated LDL eluted from a Sepharose CL-6B column similarly to native LDL so that the modified particle remained intact. 31P NMR spectra of trypsin-treated LDL showed little or no immobilized phospholipid. The immobilization in the native LDL particle is attributed to lipid-protein interactions between 1/5 of the phospholipid and the B peptide.", "contents": "Phospholipid-protein interactions in human low density lipoprotein detected by 31P nuclear magnetic resonance. 31P nuclear magnetic resonance (NMR) spectra of human low density lipoprotein (LDL) has been obtained and the major phospholipid components identified. Analysis of the spectra revealed two phospholipid environments: one occupied by 4/5 of the phospholipid with high resolution resonances possessing properties similar to phospholipids in vesicles, and a second occupied by 1/5 of the phospholipid with broad lines indicative of immobilization. Limited trypsin treatment of the particle cleaved all of the B peptide into smaller molecular weight peptides which remained with the particle. Trypsin-treated LDL eluted from a Sepharose CL-6B column similarly to native LDL so that the modified particle remained intact. 31P NMR spectra of trypsin-treated LDL showed little or no immobilized phospholipid. The immobilization in the native LDL particle is attributed to lipid-protein interactions between 1/5 of the phospholipid and the B peptide."}
{"id": "PMID:196636", "title": "Nitrite and nitric oxide treatment of Helix pomatia hemocyanin: single and double oxidation of the active site.", "content": "The reaction of nitrite and nitric oxide with Helix pomatia hemocyanin has been studied. One or both of the two copper ions in the active site can be oxidized, depending upon reaction conditions. The single oxidation of the oxygen binding site can be reversed by reduction with hydroxylamine, and the oxygen binding properties of the protein are simultaneously restored. The experiments, including electron paramagnetic resonance, indicate that nitric oxide is not a ligand of copper in the singly oxidized active site and that the oxidized copper ions is coupled to at least two nitrogen atoms of amino acid residues. The doubly oxidized protein can be reduced to a singly oxidized one with ascorbic acid or hydroxylamine; the latter reagent is again able to reduce the singly oxidized state and to restore the oxygen binding properties.", "contents": "Nitrite and nitric oxide treatment of Helix pomatia hemocyanin: single and double oxidation of the active site. The reaction of nitrite and nitric oxide with Helix pomatia hemocyanin has been studied. One or both of the two copper ions in the active site can be oxidized, depending upon reaction conditions. The single oxidation of the oxygen binding site can be reversed by reduction with hydroxylamine, and the oxygen binding properties of the protein are simultaneously restored. The experiments, including electron paramagnetic resonance, indicate that nitric oxide is not a ligand of copper in the singly oxidized active site and that the oxidized copper ions is coupled to at least two nitrogen atoms of amino acid residues. The doubly oxidized protein can be reduced to a singly oxidized one with ascorbic acid or hydroxylamine; the latter reagent is again able to reduce the singly oxidized state and to restore the oxygen binding properties."}
{"id": "PMID:196639", "title": "Structural studies on the sialic acid polysaccharide antigen of Escherichia coli strain Bos-12.", "content": "A polysaccharide, antigenically related to group C meningococcus, has been isolated from Escherichia coli strain Bos-12 (016; K92; NM). Like groups B and C meningococcal polysaccharide, the Bos-12 antigen is a pure polymer of sialic acid. 13C NMR studies on the meningococcal group B and C polysaccharides have indicated that the former consists of sialic acid units linked 2 leads to 8- alpha, whereas the latter contains the sialic acid residues linked 2 leads to 9-alpha (Bhattacharjee, A.K., Jennings, H.J., Kenny, C.P., Martin, A., and Smith, I.C.P. (1975), J. Biol. Chem. 250, 1926). Comparison of natural abundance 13C NMR spectra of the Bos-12 polysaccharide with group B and C meningococcal polysaccharides established that Bos-12 was either (a) an equimolar mixture of 2 leads to 8-alpha linked sialic acid homopolymers or (b) a 2 leads to 8-alpha/2 leads to 9-alpha heteropolymer. These possibilities were distinguished in the following manner. The fact that Bos-12 polysaccharide precipitated with anti-group C serum but not with anti-group B serum would seem to exclude a. Further, chemical studies (periodate oxidation followed by tritiated NaBH4 reduction) gave saccharides with a radioactive-labeling pattern expected for alternating 2 leads to 8-alpha/2 leads to 9-alpha sialic acid linkages. Bos-12 is thus an 2 leads to 8/2 lead to 9-alpha heteropolymer.", "contents": "Structural studies on the sialic acid polysaccharide antigen of Escherichia coli strain Bos-12. A polysaccharide, antigenically related to group C meningococcus, has been isolated from Escherichia coli strain Bos-12 (016; K92; NM). Like groups B and C meningococcal polysaccharide, the Bos-12 antigen is a pure polymer of sialic acid. 13C NMR studies on the meningococcal group B and C polysaccharides have indicated that the former consists of sialic acid units linked 2 leads to 8- alpha, whereas the latter contains the sialic acid residues linked 2 leads to 9-alpha (Bhattacharjee, A.K., Jennings, H.J., Kenny, C.P., Martin, A., and Smith, I.C.P. (1975), J. Biol. Chem. 250, 1926). Comparison of natural abundance 13C NMR spectra of the Bos-12 polysaccharide with group B and C meningococcal polysaccharides established that Bos-12 was either (a) an equimolar mixture of 2 leads to 8-alpha linked sialic acid homopolymers or (b) a 2 leads to 8-alpha/2 leads to 9-alpha heteropolymer. These possibilities were distinguished in the following manner. The fact that Bos-12 polysaccharide precipitated with anti-group C serum but not with anti-group B serum would seem to exclude a. Further, chemical studies (periodate oxidation followed by tritiated NaBH4 reduction) gave saccharides with a radioactive-labeling pattern expected for alternating 2 leads to 8-alpha/2 leads to 9-alpha sialic acid linkages. Bos-12 is thus an 2 leads to 8/2 lead to 9-alpha heteropolymer."}
{"id": "PMID:196640", "title": "Modification of ribonucleic acid by vitamin B6. 1. Specific interaction of pyridoxal 5'-phosphate with transfer ribonucleic acid.", "content": "Whole tRNA preparation obtained from a human cell line (HT-29) of colon carcinoma and purified specific Escherichia coli tRNA were reacted with pyridoxal 5'-phosphate, reduced by sodium borohydride and digested with RNase A and snake venom phosphodiesterase. Two-dimensional chromatography of the pyridoxal 5'-phosphate treated tRNA digest showed that pyridoxal 5'-phosphate binds specifically to GMP, presumably in the form of a Schiff base with the exocyclic amino group of the purine. The reaction of pyridoxal 5'-phosphate with whole tRNA was competitively inhibited by N-acetoxy-2-acetylaminofluorene. This suggests that binding occurred primarily to the G20 base residue at the unpaired region of the dihydrouridine loop (Fujimura et al., 1972). The modification of tRNA by pyridoxal 5'-phosphate resulted in the inhibition, to varying extent (10-80%), of amino acid acceptance in the aminoacyl-tRNA synthetase reaction. Defects in codon recognition by pyridoxal 5'-phosphate modified amino acid acylated tRNAs in the presence of the corresponding guanine-containing polynucleotide triplets were observed by the ribosomal binding assay.", "contents": "Modification of ribonucleic acid by vitamin B6. 1. Specific interaction of pyridoxal 5'-phosphate with transfer ribonucleic acid. Whole tRNA preparation obtained from a human cell line (HT-29) of colon carcinoma and purified specific Escherichia coli tRNA were reacted with pyridoxal 5'-phosphate, reduced by sodium borohydride and digested with RNase A and snake venom phosphodiesterase. Two-dimensional chromatography of the pyridoxal 5'-phosphate treated tRNA digest showed that pyridoxal 5'-phosphate binds specifically to GMP, presumably in the form of a Schiff base with the exocyclic amino group of the purine. The reaction of pyridoxal 5'-phosphate with whole tRNA was competitively inhibited by N-acetoxy-2-acetylaminofluorene. This suggests that binding occurred primarily to the G20 base residue at the unpaired region of the dihydrouridine loop (Fujimura et al., 1972). The modification of tRNA by pyridoxal 5'-phosphate resulted in the inhibition, to varying extent (10-80%), of amino acid acceptance in the aminoacyl-tRNA synthetase reaction. Defects in codon recognition by pyridoxal 5'-phosphate modified amino acid acylated tRNAs in the presence of the corresponding guanine-containing polynucleotide triplets were observed by the ribosomal binding assay."}
{"id": "PMID:196642", "title": "Relationship between hydroxypyruvate and the production of oxalate in vitro.", "content": "Chicken liver lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC1.1.1.27) catalyses the reversible reduction reaction of hydroxypyruvate to L-glycerate. It also catalyses the oxidation reaction of the hydrated form of glyoxylate to oxalate and the reduction of the non-hydrated form of glyoxylate to oxalate and the reduction of the non-hydrated form to glycolate. At pH 8, these latter two reactions are coupled. The coupled system equilibrium is attained when the NAD+/NADH ratio is greater than unity. Hydroxypyruvate binds to the enzyme at the same site as the pyruvate. When there are substances with greater affinity to this site in the reaction medium and their concentration is very high, hydroxypyruvate binds to the enzyme at the L-lactate site. In vitro and with purified preparation of lactate dehydrogenase, hydroxypyruvate stimulates the production of oxalate from glyoxylate-hydrated form and from NAD; the effect is due to the fact that hydroxypyruvate prevents the binding of non-hydrated form of glyoxylate to the lactate dehydrogenase in the pyruvate binding site. At pH 8, THE L-glycerate stimulates the production of glycolate from glyoxylate-non-hydrated form and NADH since hydroxypyruvate prevents the binding of glyoxylate-hydrated form to the enzyme", "contents": "Relationship between hydroxypyruvate and the production of oxalate in vitro. Chicken liver lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC1.1.1.27) catalyses the reversible reduction reaction of hydroxypyruvate to L-glycerate. It also catalyses the oxidation reaction of the hydrated form of glyoxylate to oxalate and the reduction of the non-hydrated form of glyoxylate to oxalate and the reduction of the non-hydrated form to glycolate. At pH 8, these latter two reactions are coupled. The coupled system equilibrium is attained when the NAD+/NADH ratio is greater than unity. Hydroxypyruvate binds to the enzyme at the same site as the pyruvate. When there are substances with greater affinity to this site in the reaction medium and their concentration is very high, hydroxypyruvate binds to the enzyme at the L-lactate site. In vitro and with purified preparation of lactate dehydrogenase, hydroxypyruvate stimulates the production of oxalate from glyoxylate-hydrated form and from NAD; the effect is due to the fact that hydroxypyruvate prevents the binding of non-hydrated form of glyoxylate to the lactate dehydrogenase in the pyruvate binding site. At pH 8, THE L-glycerate stimulates the production of glycolate from glyoxylate-non-hydrated form and NADH since hydroxypyruvate prevents the binding of glyoxylate-hydrated form to the enzyme"}
{"id": "PMID:196644", "title": "Effect of temperature on arginine incorporation by ribosomeless extracts of cells transformed by a temperature-sensitive mutant of Rous sarcoma virus.", "content": "The effect of transformation of normal rat kidney cells by a temperature-sensitive mutant of the Prague strain of Rous sarcoma virus (ts LA 24 PR-A) on the post-translational addition of arginine to the NH2-terminus of preformed acceptor molecules has been studied. Cells maintained at the permissive (35 degrees C) temperature show a high arginine-incorporating activity in ribosome free extracts compared to that found in extracts of cells grown at the non-permissive (40 degrees C) temperature. Temperature shift experiments as well as studies with cells transformed by wild type Rous sarcoma virus suggest that the decreased activity in cells grown at 40 degrees C is not due to a high temperature per se. The lower arginine incorporation in the 40 degrees C cell extracts is partially due to a decrease in the activity of arginyl transferase which catalyses the transfer of arginine from arginyl tRNA to the acceptor protein. Polyacrylamide gel electrophoresis of the radioactive product shows that the acceptor molecules present in extracts of cells grown at 40 degrees C are larger and qualitatively different from those found in extracts of cells grown at 35 degrees C.", "contents": "Effect of temperature on arginine incorporation by ribosomeless extracts of cells transformed by a temperature-sensitive mutant of Rous sarcoma virus. The effect of transformation of normal rat kidney cells by a temperature-sensitive mutant of the Prague strain of Rous sarcoma virus (ts LA 24 PR-A) on the post-translational addition of arginine to the NH2-terminus of preformed acceptor molecules has been studied. Cells maintained at the permissive (35 degrees C) temperature show a high arginine-incorporating activity in ribosome free extracts compared to that found in extracts of cells grown at the non-permissive (40 degrees C) temperature. Temperature shift experiments as well as studies with cells transformed by wild type Rous sarcoma virus suggest that the decreased activity in cells grown at 40 degrees C is not due to a high temperature per se. The lower arginine incorporation in the 40 degrees C cell extracts is partially due to a decrease in the activity of arginyl transferase which catalyses the transfer of arginine from arginyl tRNA to the acceptor protein. Polyacrylamide gel electrophoresis of the radioactive product shows that the acceptor molecules present in extracts of cells grown at 40 degrees C are larger and qualitatively different from those found in extracts of cells grown at 35 degrees C."}
{"id": "PMID:196645", "title": "Adenosine 3',5'-monophosphate-dependent protein kinases of myocardial non-histone nuclear proteins.", "content": "Myocardial acidic non-histone nuclear proteins (NHPs) contain endogenous protein kinase activity. Phosphocellulose chromatography of purified NHPs identifies nine separate peaks of protein kinases which can phosphorylate both endogenous and exogenous substrates to a variable degree; endogenous NHPs are the best substrates. Cyclic AMP-stimulated protein kinase induced phosphorylation of endogenous and exogenous substrates; the extent of this stimulation varied according to the protein kinase fraction and substrate used. Cyclic AMP also enhanced NHP-induced stimulation of RNA polymerase activity. This enhancement was dependent on protein kinase-induced phosphorylation of NHPs since it was prevented by alkaline phosphatase pretreatment. It is concluded that nuclear protein kinases regulate myocardial RNA synthesis by enhancing phosphorylation of NHPs and that this regulation is under cyclic AMP control.", "contents": "Adenosine 3',5'-monophosphate-dependent protein kinases of myocardial non-histone nuclear proteins. Myocardial acidic non-histone nuclear proteins (NHPs) contain endogenous protein kinase activity. Phosphocellulose chromatography of purified NHPs identifies nine separate peaks of protein kinases which can phosphorylate both endogenous and exogenous substrates to a variable degree; endogenous NHPs are the best substrates. Cyclic AMP-stimulated protein kinase induced phosphorylation of endogenous and exogenous substrates; the extent of this stimulation varied according to the protein kinase fraction and substrate used. Cyclic AMP also enhanced NHP-induced stimulation of RNA polymerase activity. This enhancement was dependent on protein kinase-induced phosphorylation of NHPs since it was prevented by alkaline phosphatase pretreatment. It is concluded that nuclear protein kinases regulate myocardial RNA synthesis by enhancing phosphorylation of NHPs and that this regulation is under cyclic AMP control."}
{"id": "PMID:196646", "title": "Interactions of some nitro-derivatives of substituted 9-aminoacridine with DNA.", "content": "The mechanism of the biological activity of the 1-nitro and 2-nitro aminoacridine derivatives containing the dimethylaminopropyl side chain was studied. RNA synthesis in the isolated rat liver nuclei was only slightly influenced by both compounds. They do not differ in their ability to form an intercalative complex with DNA. Only the 1-nitro derivative exhibited strong inhibitory effect on RNA biosynthesis and caused distinct ultrastructural changes (nucleolar segregation, chromatine margination etc.) in a living cell. The 1-nitro derivative binds covalently to DNA in vivo resulting in crosslink formation. It is concluded that the biological activity of 1-nitro acridine derivatives depends more on their crosslinking activity than on their ability to intercalate into DNA.", "contents": "Interactions of some nitro-derivatives of substituted 9-aminoacridine with DNA. The mechanism of the biological activity of the 1-nitro and 2-nitro aminoacridine derivatives containing the dimethylaminopropyl side chain was studied. RNA synthesis in the isolated rat liver nuclei was only slightly influenced by both compounds. They do not differ in their ability to form an intercalative complex with DNA. Only the 1-nitro derivative exhibited strong inhibitory effect on RNA biosynthesis and caused distinct ultrastructural changes (nucleolar segregation, chromatine margination etc.) in a living cell. The 1-nitro derivative binds covalently to DNA in vivo resulting in crosslink formation. It is concluded that the biological activity of 1-nitro acridine derivatives depends more on their crosslinking activity than on their ability to intercalate into DNA."}
{"id": "PMID:196647", "title": "Yaba virus-specific DNA in the host cell nucleus.", "content": "DNA-DNA hybridization studies show that Yaba virus-specific DNA is present in the host cell nucleus late in the infection cycle. The nuclear DNA appears to exist as a complete genome, not convalently linked to host cell DNA, as demonstrated by sedimentation analyses. The DNA apperas to be synthesized in the nucleus, since its level of incorporation of label is ten times the background incorporation detectable in the cytoplasm. Extraction of the nuclei by treatment with SDS and EDTA after precipitation with 1 M NaCl separates most of cellular DNA from the Yaba virus-specific DNA.", "contents": "Yaba virus-specific DNA in the host cell nucleus. DNA-DNA hybridization studies show that Yaba virus-specific DNA is present in the host cell nucleus late in the infection cycle. The nuclear DNA appears to exist as a complete genome, not convalently linked to host cell DNA, as demonstrated by sedimentation analyses. The DNA apperas to be synthesized in the nucleus, since its level of incorporation of label is ten times the background incorporation detectable in the cytoplasm. Extraction of the nuclei by treatment with SDS and EDTA after precipitation with 1 M NaCl separates most of cellular DNA from the Yaba virus-specific DNA."}
{"id": "PMID:196648", "title": "Studies on viral DNA protein complexes isolated at different times after infection of monkey kidney cells with simian virus 40.", "content": "The major protein components of the DNA complex, isolated from SV40-infected monkey cells, are the major viral structural polypeptide VP1 and cellular histones. At early times (24 h) after infection, VP1 is present in large amounts relative to histones, whereas at late times (48 h), the complex contains mostly histones. The amount of VP1 in the complex can be correlated to the amount of \"free\" VP1 present in the cells, i.e. VP1 not yet incorporated into virus particles. At early times about 40% of VP1 is \"free\" VP1; at late times, most of the VP1 is incorporated into virus particles. In contrast, viral DNA is produced in huge excess and only about 13% is incorporated into virions. In agreement with the above result, we find that only about 16% of the DNA in the DNA complex can be chased into virions. There is, apparently, no turnover of newly synthesized VP1 that is associated with the DNA complex at late times after infection.", "contents": "Studies on viral DNA protein complexes isolated at different times after infection of monkey kidney cells with simian virus 40. The major protein components of the DNA complex, isolated from SV40-infected monkey cells, are the major viral structural polypeptide VP1 and cellular histones. At early times (24 h) after infection, VP1 is present in large amounts relative to histones, whereas at late times (48 h), the complex contains mostly histones. The amount of VP1 in the complex can be correlated to the amount of \"free\" VP1 present in the cells, i.e. VP1 not yet incorporated into virus particles. At early times about 40% of VP1 is \"free\" VP1; at late times, most of the VP1 is incorporated into virus particles. In contrast, viral DNA is produced in huge excess and only about 13% is incorporated into virions. In agreement with the above result, we find that only about 16% of the DNA in the DNA complex can be chased into virions. There is, apparently, no turnover of newly synthesized VP1 that is associated with the DNA complex at late times after infection."}
{"id": "PMID:196649", "title": "The mechanism of ADP-ribosylation of elongation factor 2 catalyzed by fragment A from diphtheria toxin.", "content": "Measurements of the initial rate of ADP-ribosylation of elongation factor 2 (EF-2) catalyzed by Fragment A from diphtheria toxin support a sequential mechanism and suggest that the reaction proceeds through a central ternary complex involving Fragment A and the substrates, EF-2 and NAD. The Michaelis constants for EF-2 and NAD are 0.15 and 1.4 muM, respectively. As determined by equilibrium gel permeation, EF-2 does not bind Fragment A significantly, alone or in the presence of adenine, ADPribose, nicotinamide or NADH. Based on these and earlier results, we propose an ordered sequential mechanism for the reaction; the sequence of binding of substrates is NAD, followed by EF-2.", "contents": "The mechanism of ADP-ribosylation of elongation factor 2 catalyzed by fragment A from diphtheria toxin. Measurements of the initial rate of ADP-ribosylation of elongation factor 2 (EF-2) catalyzed by Fragment A from diphtheria toxin support a sequential mechanism and suggest that the reaction proceeds through a central ternary complex involving Fragment A and the substrates, EF-2 and NAD. The Michaelis constants for EF-2 and NAD are 0.15 and 1.4 muM, respectively. As determined by equilibrium gel permeation, EF-2 does not bind Fragment A significantly, alone or in the presence of adenine, ADPribose, nicotinamide or NADH. Based on these and earlier results, we propose an ordered sequential mechanism for the reaction; the sequence of binding of substrates is NAD, followed by EF-2."}
{"id": "PMID:196650", "title": "Dissociation of phosphohistone phosphatases from canine heart.", "content": "Phosphohistone phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) of canine heart extract has been separated by DEAE-cellulose chromatography into 4 molecular forms, namely phosphatases A (Mr = 156 000), B (Mr = 161 000), C (Mr = 95 600) and U (Mr = 61 000). ATP inhibited phosphatase A, stimulated phosphatase B and did not significantly affect phosphatase C activity. Phosphatase U requires Mn2+ for activity, under which condition ATP is inhibitory. Phosphatases A, B and C, but not phosphatase U, were dissociated by ethanol into catalytic subunits that were inhibited by ATP, insensitive to Mn2+, and had a common molecular weight of 34 800 (phosphatase S). The dissociation was accompanied by an increase of enzymic activity. Chromatography of the ethanol-treated 55% (NH4)2SO4 fraction of canine heart extract on DEAE-cellulose demonstrated that the multiple forms of phosphohistone phosphatase could be reduced to two forms: phosphatase U and phosphatase S, which may represent two basic constituents of the multiple forms of phosphohistone phosphatase in canine heart.", "contents": "Dissociation of phosphohistone phosphatases from canine heart. Phosphohistone phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) of canine heart extract has been separated by DEAE-cellulose chromatography into 4 molecular forms, namely phosphatases A (Mr = 156 000), B (Mr = 161 000), C (Mr = 95 600) and U (Mr = 61 000). ATP inhibited phosphatase A, stimulated phosphatase B and did not significantly affect phosphatase C activity. Phosphatase U requires Mn2+ for activity, under which condition ATP is inhibitory. Phosphatases A, B and C, but not phosphatase U, were dissociated by ethanol into catalytic subunits that were inhibited by ATP, insensitive to Mn2+, and had a common molecular weight of 34 800 (phosphatase S). The dissociation was accompanied by an increase of enzymic activity. Chromatography of the ethanol-treated 55% (NH4)2SO4 fraction of canine heart extract on DEAE-cellulose demonstrated that the multiple forms of phosphohistone phosphatase could be reduced to two forms: phosphatase U and phosphatase S, which may represent two basic constituents of the multiple forms of phosphohistone phosphatase in canine heart."}
{"id": "PMID:196653", "title": "The detection and characterisation of collagenase inhibitors from rabbit tissues in culture.", "content": "As tissue cultures, rabbit bone, skin and non-gravid uterus synthesise inhibitors of collagenase (EC 3.4.24.3). An assay for the inhibitors is described and their action on collagenase from different tissue sources demonstrated. Evidence for the involvement of the tissue inhibitors of collagenase in the latency of the enzyme in culture media is presented. Latent collagenase was activated by treatment with 4-aminophenylmercuric acetate, and then reacted with the inhibitors to form inactive complexes with properties similar to the naturally occurring latent enzyme forms. The associated changes in molecular weight are detailed, and discussed in relation to the observations of other workers concerning the extracellular control of collagenase activity.", "contents": "The detection and characterisation of collagenase inhibitors from rabbit tissues in culture. As tissue cultures, rabbit bone, skin and non-gravid uterus synthesise inhibitors of collagenase (EC 3.4.24.3). An assay for the inhibitors is described and their action on collagenase from different tissue sources demonstrated. Evidence for the involvement of the tissue inhibitors of collagenase in the latency of the enzyme in culture media is presented. Latent collagenase was activated by treatment with 4-aminophenylmercuric acetate, and then reacted with the inhibitors to form inactive complexes with properties similar to the naturally occurring latent enzyme forms. The associated changes in molecular weight are detailed, and discussed in relation to the observations of other workers concerning the extracellular control of collagenase activity."}
{"id": "PMID:196654", "title": "Kinetic studies of the old yellow enzyme. I. The reaction mechanism of the enzyme with reduced nicotinamide adenine dinucleotide.", "content": "The reaction mechanism of old yellow enzyme (NADPH:(acceptor) oxidoreductase, EC 1.6.99.1) was kinetically investigated using NADH as substrate. The enzyme was reduced by NADH via a reaction intermediate which has a specific absorption spectrum. This intermediate decomposed to yield a reduced enzyme and NAD+ through an inrreversible first-order reaction step. The reduced enzyme was reoxidized by oxygen through a second-order reaction process. Individual values of elementary rate constants were measured and a computer simulation of the reaction process was carried out. No involvement of free radical of flavin semiquinone in the reaction process could be shown.", "contents": "Kinetic studies of the old yellow enzyme. I. The reaction mechanism of the enzyme with reduced nicotinamide adenine dinucleotide. The reaction mechanism of old yellow enzyme (NADPH:(acceptor) oxidoreductase, EC 1.6.99.1) was kinetically investigated using NADH as substrate. The enzyme was reduced by NADH via a reaction intermediate which has a specific absorption spectrum. This intermediate decomposed to yield a reduced enzyme and NAD+ through an inrreversible first-order reaction step. The reduced enzyme was reoxidized by oxygen through a second-order reaction process. Individual values of elementary rate constants were measured and a computer simulation of the reaction process was carried out. No involvement of free radical of flavin semiquinone in the reaction process could be shown."}
{"id": "PMID:196655", "title": "Regulation of low density lipoprotein receptor activity by cultured human arterial smooth muscle cells.", "content": "The ability of cultured human arterial smooth muscle cells to regulate low density lipoprotein (LDL) receptor activity was tested. In contrast to human skin fibroblasts incubated with lipoprotein deficient medium under identical conditions, smooth muscle cells showed significantly reduced enhancement of 125I-labeled LDL and 125I-labeled VLDL (very low density lipoprotein) binding. Smooth muscle cells also failed to suppress LDL receptor activity during incubation with either LDL or cholesterol added to the medium, while fibroblasts shoed an active regulatory response. Thus, in comparison with the brisk LDL receptor regulation characteristic of skin fibroblasts, arterial smooth muscle cells have and attenuated capacity to regulate their LDL receptor activity. These results may be relevant to the propensity of these cells to accumulate LDL and cholesterol and form \"foam cells\" in the arterial wall in vivo, a process associated with atherogenesis.", "contents": "Regulation of low density lipoprotein receptor activity by cultured human arterial smooth muscle cells. The ability of cultured human arterial smooth muscle cells to regulate low density lipoprotein (LDL) receptor activity was tested. In contrast to human skin fibroblasts incubated with lipoprotein deficient medium under identical conditions, smooth muscle cells showed significantly reduced enhancement of 125I-labeled LDL and 125I-labeled VLDL (very low density lipoprotein) binding. Smooth muscle cells also failed to suppress LDL receptor activity during incubation with either LDL or cholesterol added to the medium, while fibroblasts shoed an active regulatory response. Thus, in comparison with the brisk LDL receptor regulation characteristic of skin fibroblasts, arterial smooth muscle cells have and attenuated capacity to regulate their LDL receptor activity. These results may be relevant to the propensity of these cells to accumulate LDL and cholesterol and form \"foam cells\" in the arterial wall in vivo, a process associated with atherogenesis."}
{"id": "PMID:196656", "title": "The effect of portacaval shunt on plasma lipids and lipoproteins in swine.", "content": "Plasma lipids and lipoprotein composition and distribution were studied in fasted miniature swine prior to and at 5 and 19 weeks following portacaval shunt surgery or a sham operation. Plasma triacylglycerol and cholesterol levels were significantly reduced in the portacaval shunt swine at 5 weeks. These reductions were accompanied by significant decreases in the plasma very low density lipoprotein (d less than 1.006), low density lipoprotein (d = 1.02-1.07) and high density lipoprotein (d = 1.09-1.21) levels. The very low density lipoprotein were shown depleted in lipids and the low density lipoprotein was a cholesterol-depleted, triacylglycerol-enriched particle. No changes in the composition of the high density lipoprotein were observed. These reductions and changes in composition were maintained until killing at 19 weeks post-surgery.", "contents": "The effect of portacaval shunt on plasma lipids and lipoproteins in swine. Plasma lipids and lipoprotein composition and distribution were studied in fasted miniature swine prior to and at 5 and 19 weeks following portacaval shunt surgery or a sham operation. Plasma triacylglycerol and cholesterol levels were significantly reduced in the portacaval shunt swine at 5 weeks. These reductions were accompanied by significant decreases in the plasma very low density lipoprotein (d less than 1.006), low density lipoprotein (d = 1.02-1.07) and high density lipoprotein (d = 1.09-1.21) levels. The very low density lipoprotein were shown depleted in lipids and the low density lipoprotein was a cholesterol-depleted, triacylglycerol-enriched particle. No changes in the composition of the high density lipoprotein were observed. These reductions and changes in composition were maintained until killing at 19 weeks post-surgery."}
{"id": "PMID:196658", "title": "Fatty acid synthetase activity in Mycobacterium smegmatis. Characterization of the acyl carrier protein-dependent elongating system.", "content": "Mycobacterium smegmatis extracts contain two fatty acyl synthetase systems (Brindley, D.N., Matsumura, S. and Bloch, K. (1966) Nature 224, 666-669). One is the extensively studied multienzyme complex, (molecular weight 1.39 - 10(6)) which produces shorter C16 and C18) and longer (C24 and higher) fatty acids in a bimodal pattern. The second synthetase is acyl carrier-protein (ACP) dependent and elongates the CoA derivatives of C12 and longer chains. In contrast to the type I synthetase which also extends long fatty acyl chains, the ACP-dependent system produces homologous fatty acids up to 30 carbon atoms long in approximately equal proportions. Other properties which distinguish the ACP-dependent system from the multienzyme complex include the resistance to high concentrations of palmitoyl-CoA and to low ionic strength and the lack of stimulation by mycobacterial polysaccharides. The possibility that the two fatty acid synthetases are complimentary in their function is discussed.", "contents": "Fatty acid synthetase activity in Mycobacterium smegmatis. Characterization of the acyl carrier protein-dependent elongating system. Mycobacterium smegmatis extracts contain two fatty acyl synthetase systems (Brindley, D.N., Matsumura, S. and Bloch, K. (1966) Nature 224, 666-669). One is the extensively studied multienzyme complex, (molecular weight 1.39 - 10(6)) which produces shorter C16 and C18) and longer (C24 and higher) fatty acids in a bimodal pattern. The second synthetase is acyl carrier-protein (ACP) dependent and elongates the CoA derivatives of C12 and longer chains. In contrast to the type I synthetase which also extends long fatty acyl chains, the ACP-dependent system produces homologous fatty acids up to 30 carbon atoms long in approximately equal proportions. Other properties which distinguish the ACP-dependent system from the multienzyme complex include the resistance to high concentrations of palmitoyl-CoA and to low ionic strength and the lack of stimulation by mycobacterial polysaccharides. The possibility that the two fatty acid synthetases are complimentary in their function is discussed."}
{"id": "PMID:196660", "title": "Role of lamellar bodies in the biosynthesis of phosphatidylcholine in mouse lung.", "content": "1. A lamellar body-enriched fraction was isolated from whole lung homogenates of mouse lung and its contamination with microsomes, mitochondria, and cytosol protein assessed by marker enzyme analyses. 2. By measuring the activity of cholinephosphotransferase (EC 2.7.8.2) in varying amounts of microsomes in the presence and absence of a fixed quantity of lamellar bodies, it could be demonstrated unequivocally that lamellar bodies of mouse lung lack the capacity to synthesize phosphatidylcholine de novo. 3. A similar approach allowed the conclusion that lamellar bodies of mouse lung do not contain lysophosphatidylcholine acyltransferase (EC 2.3.1.23) and lysophosphatidylcholine:lysophosphatidylcholine acyltransferase (EC 2.3.1.--), enzymes which play a putative role in the formation of pulmonary 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine. The activities of these enzymes observed in lamellar body fractions could be attributed completely to contaminating microsomes and cytosol respectively. 4. Lamellar bodies contributed to the activity of microsomal lysophosphatidylcholine acyltransferase by a cooperative effect. The possible role of this cooperation in the biosynthesis of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine is discussed.", "contents": "Role of lamellar bodies in the biosynthesis of phosphatidylcholine in mouse lung. 1. A lamellar body-enriched fraction was isolated from whole lung homogenates of mouse lung and its contamination with microsomes, mitochondria, and cytosol protein assessed by marker enzyme analyses. 2. By measuring the activity of cholinephosphotransferase (EC 2.7.8.2) in varying amounts of microsomes in the presence and absence of a fixed quantity of lamellar bodies, it could be demonstrated unequivocally that lamellar bodies of mouse lung lack the capacity to synthesize phosphatidylcholine de novo. 3. A similar approach allowed the conclusion that lamellar bodies of mouse lung do not contain lysophosphatidylcholine acyltransferase (EC 2.3.1.23) and lysophosphatidylcholine:lysophosphatidylcholine acyltransferase (EC 2.3.1.--), enzymes which play a putative role in the formation of pulmonary 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine. The activities of these enzymes observed in lamellar body fractions could be attributed completely to contaminating microsomes and cytosol respectively. 4. Lamellar bodies contributed to the activity of microsomal lysophosphatidylcholine acyltransferase by a cooperative effect. The possible role of this cooperation in the biosynthesis of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine is discussed."}
{"id": "PMID:196663", "title": "Two copper-containing proteins from white and gray matter of brain.", "content": "The procedure for the isolation of two water soluble copper-containing proteins from the white and gray matter of bovine brain is described. One of the proteins, cerebrocuprein I, is superoxide dismutase; and three molecular forms of this enzyme are to be found in brain. The other protein present in gray and white matter is devoid of superoxide dismutase and amine oxidase activities. The amino acid composition, molecular weight, isoelectric point and copper content of this protein were determined. The effect of some agents, pH and thermal treatment of the optical and EPR spectra of the protein were also studied. The copper of the protein may be removed and the holoprotein reconstituted again from apoprotein and copper. The results obtained led to the conclusion that in brain a new copper protein is discovered, which is named neurocuprein.", "contents": "Two copper-containing proteins from white and gray matter of brain. The procedure for the isolation of two water soluble copper-containing proteins from the white and gray matter of bovine brain is described. One of the proteins, cerebrocuprein I, is superoxide dismutase; and three molecular forms of this enzyme are to be found in brain. The other protein present in gray and white matter is devoid of superoxide dismutase and amine oxidase activities. The amino acid composition, molecular weight, isoelectric point and copper content of this protein were determined. The effect of some agents, pH and thermal treatment of the optical and EPR spectra of the protein were also studied. The copper of the protein may be removed and the holoprotein reconstituted again from apoprotein and copper. The results obtained led to the conclusion that in brain a new copper protein is discovered, which is named neurocuprein."}
{"id": "PMID:196666", "title": "Calcium and pancreatic beta-cell function. I. Stimulatory effects of pentobarbital on insulin release.", "content": "Islets microdissected from ob/ob-mice were exposed to 3mM pentobarbital in media which were normal or deficient in Ca2+. This treatment resulted in marked decrease of the islet content of cyclic AMP recorded in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Pentobarbital had a dual effect on insulin release. In addition to being a potent inhibitor of glucose-stimulated insulin release in media containing 2.56 mM Ca2+ it increased the amounts of insulin released in high glucose media deficient in Ca2+. There was a transient stimulation with ordinary concentrations of Ca2+ and 3mM glucose whtn the media also contained 3-isobutyl-1-methylxanthine. The stimulatory effect of pentobarbital persisted after replacing part of the Ca2+ in the beta-cell membrane with lanthanum ions and it could not be mimicked by lowering the oxygen tension of the incubation medium. It is suggested that pentobarbital stimulation of insulin release is the result of a specific action of the drug on the distribution of Ca2+ within the pancreatic beta-cells.", "contents": "Calcium and pancreatic beta-cell function. I. Stimulatory effects of pentobarbital on insulin release. Islets microdissected from ob/ob-mice were exposed to 3mM pentobarbital in media which were normal or deficient in Ca2+. This treatment resulted in marked decrease of the islet content of cyclic AMP recorded in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Pentobarbital had a dual effect on insulin release. In addition to being a potent inhibitor of glucose-stimulated insulin release in media containing 2.56 mM Ca2+ it increased the amounts of insulin released in high glucose media deficient in Ca2+. There was a transient stimulation with ordinary concentrations of Ca2+ and 3mM glucose whtn the media also contained 3-isobutyl-1-methylxanthine. The stimulatory effect of pentobarbital persisted after replacing part of the Ca2+ in the beta-cell membrane with lanthanum ions and it could not be mimicked by lowering the oxygen tension of the incubation medium. It is suggested that pentobarbital stimulation of insulin release is the result of a specific action of the drug on the distribution of Ca2+ within the pancreatic beta-cells."}
{"id": "PMID:196667", "title": "Cyclic GMP-dependent and cyclic AMP-dependent protein kinases, protein kinase modulators and phosphodiesterases in arteries and veins of dogs. Distribution and effects of arteriovenous fistula and arterial occlusion.", "content": "Possible involvement of cyclic GMP-dependent and cyclic AMP-dependent protein kinases, protein kinase modulators and cyclic nucleotide phosphodiesterases in functions of vascular tissues were investigated in the dog. All of the above activities, localized in the smooth muscle-rich inner layer of the blood vessels, were found to be higher in the arteries than in the veins. The peripheral arteries were disproportionately richer in cyclic GMP-dependent protein kinase (as indicated by high ratios of cyclic GMP-dependent to cyclic AMP-dependent protein kinase) than were the veins, with the exception of the pulmonary artery, an atypical arterial tissue exposed to low blood pressure. Interestingly, the protein kinase ratio for the aorta, an artery with no significant role in blood pressure regulation, was not higher than that for the vena cava. Creation of femoral arteriovenous fistulae in the dogs led to preferential reductions in the cyclic GMP-dependent enzyme activity both in the proximal and distal arteries, whereas it was elevated in the stressed vein distal to the anastomotic site. The cyclic GMP-dependent enzyme was preferentially reduced in the saphenous artery distal to occlusion. Changes in the cyclic GMP-dependent enzyme activity appeared to precede gross atrophy or hypertrophy of the vessels. It is suggested that the vascular cyclic GMP-dependent protein kinase may be closely related to peripheral resistance and its regulation.", "contents": "Cyclic GMP-dependent and cyclic AMP-dependent protein kinases, protein kinase modulators and phosphodiesterases in arteries and veins of dogs. Distribution and effects of arteriovenous fistula and arterial occlusion. Possible involvement of cyclic GMP-dependent and cyclic AMP-dependent protein kinases, protein kinase modulators and cyclic nucleotide phosphodiesterases in functions of vascular tissues were investigated in the dog. All of the above activities, localized in the smooth muscle-rich inner layer of the blood vessels, were found to be higher in the arteries than in the veins. The peripheral arteries were disproportionately richer in cyclic GMP-dependent protein kinase (as indicated by high ratios of cyclic GMP-dependent to cyclic AMP-dependent protein kinase) than were the veins, with the exception of the pulmonary artery, an atypical arterial tissue exposed to low blood pressure. Interestingly, the protein kinase ratio for the aorta, an artery with no significant role in blood pressure regulation, was not higher than that for the vena cava. Creation of femoral arteriovenous fistulae in the dogs led to preferential reductions in the cyclic GMP-dependent enzyme activity both in the proximal and distal arteries, whereas it was elevated in the stressed vein distal to the anastomotic site. The cyclic GMP-dependent enzyme was preferentially reduced in the saphenous artery distal to occlusion. Changes in the cyclic GMP-dependent enzyme activity appeared to precede gross atrophy or hypertrophy of the vessels. It is suggested that the vascular cyclic GMP-dependent protein kinase may be closely related to peripheral resistance and its regulation."}
{"id": "PMID:196668", "title": "Protein phosphorylation in a dopamine-sensitive homogenate of rat caudate. Effect of adenosine 3',5'-cyclic monophosphate and putative neurotransmitters.", "content": "Adenosine 3',5'-cyclic monophosphate (cyclic AMP) and its 8-methylthio derivative stimulate the incorporation of 32P into proteins endogenous to a homogenate of rat caudate nucleus when 4 micrometer [gamma-32P] ATP is used as substrate. Higher concentrations of ATP reduced the effect of the cyclic nucleotide until at 400 micrometer no significant increase in protein phosphorylation was seen. Incubation of the homogenate with 400 micron ATP and 100 micron dopamine resulted in an approx. 2-fold increase in cyclic AMP but did not alter caudate protein phosphorylation suggesting that the catecholamine could not stimulate protein phosphorylation under the experimental conditions used in the present study.", "contents": "Protein phosphorylation in a dopamine-sensitive homogenate of rat caudate. Effect of adenosine 3',5'-cyclic monophosphate and putative neurotransmitters. Adenosine 3',5'-cyclic monophosphate (cyclic AMP) and its 8-methylthio derivative stimulate the incorporation of 32P into proteins endogenous to a homogenate of rat caudate nucleus when 4 micrometer [gamma-32P] ATP is used as substrate. Higher concentrations of ATP reduced the effect of the cyclic nucleotide until at 400 micrometer no significant increase in protein phosphorylation was seen. Incubation of the homogenate with 400 micron ATP and 100 micron dopamine resulted in an approx. 2-fold increase in cyclic AMP but did not alter caudate protein phosphorylation suggesting that the catecholamine could not stimulate protein phosphorylation under the experimental conditions used in the present study."}
{"id": "PMID:196669", "title": "Effects of calcitonin and parathyroid hormone on the metabolism of chondrocytes in culture.", "content": "Rabbit articular chondrocytes in suspension culture synthesize Type II collagen [3alpha1(II)] in the absence of extracellular Ca2+ and Type I collagen [2alpha1(I) - alpha2] in the complete medium. As a result of pre-treatment in monolayer culture with calcitonin or parathyroid hormone in the complete medium, an influx of Ca2+ into the cells occurs. These cells produce mainly Type I collagen when transferred to suspension cultures in the medium devoid of CaCl2. If added directly to the suspension culture medium containing no CaCl2, calcitonin stimulates an active efflux of Ca2+ from the cells into the medium and leads the cells to synthesize Type I collagen. Under similar conditions, parathyroid hormone does not change the collagen-phenotype.", "contents": "Effects of calcitonin and parathyroid hormone on the metabolism of chondrocytes in culture. Rabbit articular chondrocytes in suspension culture synthesize Type II collagen [3alpha1(II)] in the absence of extracellular Ca2+ and Type I collagen [2alpha1(I) - alpha2] in the complete medium. As a result of pre-treatment in monolayer culture with calcitonin or parathyroid hormone in the complete medium, an influx of Ca2+ into the cells occurs. These cells produce mainly Type I collagen when transferred to suspension cultures in the medium devoid of CaCl2. If added directly to the suspension culture medium containing no CaCl2, calcitonin stimulates an active efflux of Ca2+ from the cells into the medium and leads the cells to synthesize Type I collagen. Under similar conditions, parathyroid hormone does not change the collagen-phenotype."}
{"id": "PMID:196670", "title": "Interrelation of prostaglandin endoperoxide (prostaglandin G2) and cyclic 3',5'-adenosine monophosphate in human blood platelets.", "content": "The prostaglandin endoperoxide, prostaglandin G2, in platelet-rich plasma may produce reversible platelet aggregation without secretion, irreversible aggregation with secretion of platelet constituents inhibited by indomethacin, or the latter effects despite indomethacin, depending on the concentration of the endoperoxide. Irreversible aggregation and platelet secretion induced by prostaglandin G2 apparently result from the action of ADP, since these responses are inhibited by 2-n-amylthio-5'-AMP (an inhibitor of the actions of ADP on platelets) and they do not occur in heparinized platelet-rich plasma. Prostaglandin G2 lowers the platelet level of cyclic 3',5'-AMP. Its actions are inhibited by elevation of cyclic AMP levels by prostaglandin E1 or dibutyryl cyclic AMP or adenosine. Like malondialdehyde production induced by thrombin, ADP, or arachidonic acid, prostaglandin G2-induced malondialdehyde production is reduced by dibutyryl cyclic AMP and prostaglandin E1. Platelet activation by prostaglandin G2 is enhanced by the adenylate cyclase inhibitor, 9-(tetrahydro-2-furyl)-adenine. The action of prostaglandin G2 on platelets is more complex then previously reported.", "contents": "Interrelation of prostaglandin endoperoxide (prostaglandin G2) and cyclic 3',5'-adenosine monophosphate in human blood platelets. The prostaglandin endoperoxide, prostaglandin G2, in platelet-rich plasma may produce reversible platelet aggregation without secretion, irreversible aggregation with secretion of platelet constituents inhibited by indomethacin, or the latter effects despite indomethacin, depending on the concentration of the endoperoxide. Irreversible aggregation and platelet secretion induced by prostaglandin G2 apparently result from the action of ADP, since these responses are inhibited by 2-n-amylthio-5'-AMP (an inhibitor of the actions of ADP on platelets) and they do not occur in heparinized platelet-rich plasma. Prostaglandin G2 lowers the platelet level of cyclic 3',5'-AMP. Its actions are inhibited by elevation of cyclic AMP levels by prostaglandin E1 or dibutyryl cyclic AMP or adenosine. Like malondialdehyde production induced by thrombin, ADP, or arachidonic acid, prostaglandin G2-induced malondialdehyde production is reduced by dibutyryl cyclic AMP and prostaglandin E1. Platelet activation by prostaglandin G2 is enhanced by the adenylate cyclase inhibitor, 9-(tetrahydro-2-furyl)-adenine. The action of prostaglandin G2 on platelets is more complex then previously reported."}
{"id": "PMID:196677", "title": "[Liberation and reassociation of the microsomal membrane glucokinase in cat liver].", "content": "The particulate glucokinase of cat liver is shown to be microsomal. The activity is readily solubilized by glucose-6-phosphate, ATP, pyrophosphate, high salt concentrations and, to a lesser extent, ribonucleoside triphosphates. The solubilization by glucose-6-phosphate is inhibited by Pi. Solubilizations by ATP and glucose-6-phosphate differ in their sensitivity to temperature changes; they are relatively specific for glucokinase as compared to solubilization by detergent (Triton X 100). The enzyme can be bound again to previously eluted microsomal membranes. Treatment of membrane with trypsin, at 0 degrees C, destroys the ability to rebind the enzyme to the membrane. It is suggested that electrostatic forces are of considerable importance for the binding of glucokinase to a possible protein binding site in the membrane.", "contents": "[Liberation and reassociation of the microsomal membrane glucokinase in cat liver]. The particulate glucokinase of cat liver is shown to be microsomal. The activity is readily solubilized by glucose-6-phosphate, ATP, pyrophosphate, high salt concentrations and, to a lesser extent, ribonucleoside triphosphates. The solubilization by glucose-6-phosphate is inhibited by Pi. Solubilizations by ATP and glucose-6-phosphate differ in their sensitivity to temperature changes; they are relatively specific for glucokinase as compared to solubilization by detergent (Triton X 100). The enzyme can be bound again to previously eluted microsomal membranes. Treatment of membrane with trypsin, at 0 degrees C, destroys the ability to rebind the enzyme to the membrane. It is suggested that electrostatic forces are of considerable importance for the binding of glucokinase to a possible protein binding site in the membrane."}
{"id": "PMID:196673", "title": "[Absorption spectra of chlorophyll a adsorbed on aerosil].", "content": "The adsorption spectra of chlorophyll a adsorbed on aerosil surface have been studied. It has been supposed that the spectral properties of adsorbed chlorophyll a layers are mainly due to the interactions between the pigment molecules. The derivative absorption spectra of adsorbed chlorophyll a have been obtained. It has been determined that descrete absorption maxima of adsorbed chlorophyll a aggregates are characteristic of the native chlorophyll a. It has been supposed that the fundamental spectral forms of chlorophyll a in vivo are reproduced in adsorbed layers of the pigment.", "contents": "[Absorption spectra of chlorophyll a adsorbed on aerosil]. The adsorption spectra of chlorophyll a adsorbed on aerosil surface have been studied. It has been supposed that the spectral properties of adsorbed chlorophyll a layers are mainly due to the interactions between the pigment molecules. The derivative absorption spectra of adsorbed chlorophyll a have been obtained. It has been determined that descrete absorption maxima of adsorbed chlorophyll a aggregates are characteristic of the native chlorophyll a. It has been supposed that the fundamental spectral forms of chlorophyll a in vivo are reproduced in adsorbed layers of the pigment."}
{"id": "PMID:196678", "title": "Effect of cyclic nucleotides in vitro assays of rat liver galactosyltransferase.", "content": "Experiments with rat liver microsomal galactosyltransferase has been developed to test the effect of cyclic nucleotides on the transfer activity. An overall stimulation is observed when cAMP or cGMP (concentration higher that 10(-6) M) are added to the incubation medium. However, more detailed experiments show that the cyclic nucleotides do not act as direct effectors of the enzyme but present the precursors degradation by the glycosylnucleotide pyrophosphatases.", "contents": "Effect of cyclic nucleotides in vitro assays of rat liver galactosyltransferase. Experiments with rat liver microsomal galactosyltransferase has been developed to test the effect of cyclic nucleotides on the transfer activity. An overall stimulation is observed when cAMP or cGMP (concentration higher that 10(-6) M) are added to the incubation medium. However, more detailed experiments show that the cyclic nucleotides do not act as direct effectors of the enzyme but present the precursors degradation by the glycosylnucleotide pyrophosphatases."}
{"id": "PMID:196674", "title": "[Effect of estrogens on interaction of calcium ions with mitochondrial membranes].", "content": "It has been shown that steroid hormones do not affect the fluorescence parameters in solutions of the complex NADH-Ca. Addition of discoupling concentrations of Ca2+ to the liver mitochondria induced the elimination of pyridine nucleotides. The hormones studied inhibit the oxidation of NAD-dependent substrates, thus suppressing an active transport of Ca2+. An analysis of the effect of steroid hormones on Ca2+ ions transport under succinate oxidation suggests that these hormones affect the polarity of hydrophobic regions of the mitochondria membranes. It is suggested that steroid hormones can perform their regulatory functions by influencing the transport of Ca2+ ions in the living cell.", "contents": "[Effect of estrogens on interaction of calcium ions with mitochondrial membranes]. It has been shown that steroid hormones do not affect the fluorescence parameters in solutions of the complex NADH-Ca. Addition of discoupling concentrations of Ca2+ to the liver mitochondria induced the elimination of pyridine nucleotides. The hormones studied inhibit the oxidation of NAD-dependent substrates, thus suppressing an active transport of Ca2+. An analysis of the effect of steroid hormones on Ca2+ ions transport under succinate oxidation suggests that these hormones affect the polarity of hydrophobic regions of the mitochondria membranes. It is suggested that steroid hormones can perform their regulatory functions by influencing the transport of Ca2+ ions in the living cell."}
{"id": "PMID:196681", "title": "[Quaternary structure of a cytoplasmic protein with ribonuclease activity from wheate seedling leaves. Kinetic manifestation of its \"native\", dissociated and reassociated forms].", "content": "Previous  data on oligomeric nature and values of molecular masses of \"native\" and dissociated forms of cytoplasmic protein with ribonulcease activity from wheat seedling leaves (Bezenchukskaya 98) are confirmed by means of polyacrylamide gel disc electrophoresis. Possible relation of the \"native\" enzyme form with 3':5'-cAMP is demonstrated by paper chromatography and the enzyme reassociation by the nucleotide. Study of kinetic manifestation of \"native\", dissociated and reassociated enzyme forms has revealed that the enzyme in the \"normal\" state has probably at least two active sites, \"negative\" homotropic cooperative interaction being establish-d between them at the definite degree of substrate saturation. The cooperativity disappears under dissociation, and it is discovered again under reassociation.", "contents": "[Quaternary structure of a cytoplasmic protein with ribonuclease activity from wheate seedling leaves. Kinetic manifestation of its \"native\", dissociated and reassociated forms]. Previous  data on oligomeric nature and values of molecular masses of \"native\" and dissociated forms of cytoplasmic protein with ribonulcease activity from wheat seedling leaves (Bezenchukskaya 98) are confirmed by means of polyacrylamide gel disc electrophoresis. Possible relation of the \"native\" enzyme form with 3':5'-cAMP is demonstrated by paper chromatography and the enzyme reassociation by the nucleotide. Study of kinetic manifestation of \"native\", dissociated and reassociated enzyme forms has revealed that the enzyme in the \"normal\" state has probably at least two active sites, \"negative\" homotropic cooperative interaction being establish-d between them at the definite degree of substrate saturation. The cooperativity disappears under dissociation, and it is discovered again under reassociation."}
{"id": "PMID:196682", "title": "[Effect of liver chromatin DNAse on closed circular DNA of PM-2 phage and simian virus 40].", "content": "Comparative effect of the DNAse from rat liver chromatin and Neurospora crassa endonuclease S1 on closed circular superhelical DNA of PM-2 phage and Simian Virus 40 is studied. It is shown that both of them--the DNAse from chromatin proteins and endonuclease S1--are specific to single-stranded regions in DNA molecular. It is suggested that chromatin protein DNAse participates in reparation processes.", "contents": "[Effect of liver chromatin DNAse on closed circular DNA of PM-2 phage and simian virus 40]. Comparative effect of the DNAse from rat liver chromatin and Neurospora crassa endonuclease S1 on closed circular superhelical DNA of PM-2 phage and Simian Virus 40 is studied. It is shown that both of them--the DNAse from chromatin proteins and endonuclease S1--are specific to single-stranded regions in DNA molecular. It is suggested that chromatin protein DNAse participates in reparation processes."}
{"id": "PMID:196684", "title": "[Investigation of lipid-exchange lipoproteins from rat liver and hepatoma 27].", "content": "A phospholipid exchange lipoprotein from the postmicrosomal supernatant of rat hepatoma 27, which stimulated in vitro the exchange of sphingomyelin between mitochondria and microsomes, was found. Sphingomyelin is incorporated into the mitochondria under incubation of this complex with rat liver mitochondria (in which sphingomyelin is absent) an microsomes. Under the same conditions the phospholipid exchange lipoproteins of rat liver do not transfer sphingomyelin form microsomes to mitochrondria.", "contents": "[Investigation of lipid-exchange lipoproteins from rat liver and hepatoma 27]. A phospholipid exchange lipoprotein from the postmicrosomal supernatant of rat hepatoma 27, which stimulated in vitro the exchange of sphingomyelin between mitochondria and microsomes, was found. Sphingomyelin is incorporated into the mitochondria under incubation of this complex with rat liver mitochondria (in which sphingomyelin is absent) an microsomes. Under the same conditions the phospholipid exchange lipoproteins of rat liver do not transfer sphingomyelin form microsomes to mitochrondria."}
{"id": "PMID:196685", "title": "[A mathematical model of the pyruvate oxidation in liver mitochondria. 1. Regulation of the Krebs cycle by adenine and pyridine nucleotides].", "content": "A mathematical model is proposed to describe the behavior of the pyruvate metabolic reactions, Krebs cycle and oxidative phosphorylation over a wide range of changes in the pyruvate influx rate and the activities of ATPase and NADH-reoxidating dehydrogenase. The role of adenine and pyridine nucleotides in various allosteric regulations of the Krebs cycle enzymes is discussed. The accumulation of ATP and NADH has been shown to proceed in definite succession, which makes the allosteric regulation of the Krebs cycle enzymes successive too. First \"works\" the inhibition by ATP, then by NADH. It has been shown that the properties of the model are in qualitative agreement with the experimental data (Garber A., Hanson R. [1]) on pyruvate oxidation by mitochondria from guinea pig liver, when allosteric regulation of isocitrate dehydrogenase by adenine nucleotides is taken into account.", "contents": "[A mathematical model of the pyruvate oxidation in liver mitochondria. 1. Regulation of the Krebs cycle by adenine and pyridine nucleotides]. A mathematical model is proposed to describe the behavior of the pyruvate metabolic reactions, Krebs cycle and oxidative phosphorylation over a wide range of changes in the pyruvate influx rate and the activities of ATPase and NADH-reoxidating dehydrogenase. The role of adenine and pyridine nucleotides in various allosteric regulations of the Krebs cycle enzymes is discussed. The accumulation of ATP and NADH has been shown to proceed in definite succession, which makes the allosteric regulation of the Krebs cycle enzymes successive too. First \"works\" the inhibition by ATP, then by NADH. It has been shown that the properties of the model are in qualitative agreement with the experimental data (Garber A., Hanson R. [1]) on pyruvate oxidation by mitochondria from guinea pig liver, when allosteric regulation of isocitrate dehydrogenase by adenine nucleotides is taken into account."}
{"id": "PMID:196686", "title": "[Isolation and some properties of protein kinase from pigeon breast muscle].", "content": "Protein kinase was isolated from pigeon breast muscle. The preparation obtained was chromatographically homogeneous. The apparent Km varlue for histone H1 and ATP were 3,5-10(-5) M and 1,6-10(-5) M respectively. The purified enzyme displays high specificity for the lysine-rich histones (H1, H2b, H2a). The protein kinase activity is stimulated, 1,6-fold by cyclic AMP.", "contents": "[Isolation and some properties of protein kinase from pigeon breast muscle]. Protein kinase was isolated from pigeon breast muscle. The preparation obtained was chromatographically homogeneous. The apparent Km varlue for histone H1 and ATP were 3,5-10(-5) M and 1,6-10(-5) M respectively. The purified enzyme displays high specificity for the lysine-rich histones (H1, H2b, H2a). The protein kinase activity is stimulated, 1,6-fold by cyclic AMP."}
{"id": "PMID:196687", "title": "[The actions of low-molecular fragments of substrate and their analogs on the activity of isoenzymes of phospholipase C from Clostridium perfringens].", "content": "The interaction of the lecithin molecule fragments and their analogues with phospholipase C Cl. perfringens was studied by gel-diffusion in agarose-lecithin gels. It was found intense inhibition of phospholipase C activity in the presence of cathionic compounds; this phenomenon shows the existence of anionic centre in the active site of enzyme. The esteric centre is probably hydrophobic nature and is not capable to bind the negatively charged groups. However, phosphoserine, phosphothreonine, gamma-aminobutyric, aspartic and glutamic acids can interact with an additional cathionic centre, whose location in phospholipase C differs from that in pancreatic phospholipase A2.", "contents": "[The actions of low-molecular fragments of substrate and their analogs on the activity of isoenzymes of phospholipase C from Clostridium perfringens]. The interaction of the lecithin molecule fragments and their analogues with phospholipase C Cl. perfringens was studied by gel-diffusion in agarose-lecithin gels. It was found intense inhibition of phospholipase C activity in the presence of cathionic compounds; this phenomenon shows the existence of anionic centre in the active site of enzyme. The esteric centre is probably hydrophobic nature and is not capable to bind the negatively charged groups. However, phosphoserine, phosphothreonine, gamma-aminobutyric, aspartic and glutamic acids can interact with an additional cathionic centre, whose location in phospholipase C differs from that in pancreatic phospholipase A2."}
{"id": "PMID:196688", "title": "[The role of 3',5'-AMP in regulation of activity of histidase from rat liver and skin].", "content": "A dependence of activity of histidase from rat liver and skin on the agents affecting the activity of the adenylate cyclase systeme was studied in vitro. Under conditions optimal for the activity of liver phosphorylase protein kinase the skin extract histidase was activated 2-3-fold. This is indicative of a possibility of regulation of the skin histidase activity via the adenylate cyclase system by modification of enzyme by phosphorylation-dephosphorylation, which is performed by 3':5'-AMP-dependent protein kinase. Theophylline at concentrations of 10(-4) M and 10(-3) M activates partially purified histidase (both liver and skin forms), probably in the course of direct interaction with the enzyme.", "contents": "[The role of 3',5'-AMP in regulation of activity of histidase from rat liver and skin]. A dependence of activity of histidase from rat liver and skin on the agents affecting the activity of the adenylate cyclase systeme was studied in vitro. Under conditions optimal for the activity of liver phosphorylase protein kinase the skin extract histidase was activated 2-3-fold. This is indicative of a possibility of regulation of the skin histidase activity via the adenylate cyclase system by modification of enzyme by phosphorylation-dephosphorylation, which is performed by 3':5'-AMP-dependent protein kinase. Theophylline at concentrations of 10(-4) M and 10(-3) M activates partially purified histidase (both liver and skin forms), probably in the course of direct interaction with the enzyme."}
{"id": "PMID:196689", "title": "[Effect of some organosilicon compounds (silatranes) on the biosynthesis of collagen in cartilagenous tissue of chick embryo].", "content": "Effect of some organosilicon compounds from the class of silatranes on the biosynthesis of collagen in cartilagenous tissue of chick embryos in vitro was studied. The criteria for assessing the intensity of collagen biosynthesis was the formation of peptide bond 14C-hydroxyproline from 14C-proline of incubation medium. All the compounds studied (methylsilatrane, ethoxysilatrane and chloromethylsilatrane) stimulated total protein biosynthesis and collagen biosynthesis in cartilagenous tissue of chick embryos. The most pronounced stimulation of the biosynthesis of collagen was observed at 3-10(-3) M concentration of silatranes within 180 min. of incubation (14C-proline was added to the incubation medium 60 min after the beginning of the incubation). The activity of partly purified collagen prolyl-hydroxylase in the presence of silatranes was also studied.", "contents": "[Effect of some organosilicon compounds (silatranes) on the biosynthesis of collagen in cartilagenous tissue of chick embryo]. Effect of some organosilicon compounds from the class of silatranes on the biosynthesis of collagen in cartilagenous tissue of chick embryos in vitro was studied. The criteria for assessing the intensity of collagen biosynthesis was the formation of peptide bond 14C-hydroxyproline from 14C-proline of incubation medium. All the compounds studied (methylsilatrane, ethoxysilatrane and chloromethylsilatrane) stimulated total protein biosynthesis and collagen biosynthesis in cartilagenous tissue of chick embryos. The most pronounced stimulation of the biosynthesis of collagen was observed at 3-10(-3) M concentration of silatranes within 180 min. of incubation (14C-proline was added to the incubation medium 60 min after the beginning of the incubation). The activity of partly purified collagen prolyl-hydroxylase in the presence of silatranes was also studied."}
{"id": "PMID:196691", "title": "Motoneuron excitability in psychiatric patients.", "content": "The excitability at the alpha-motoneuron pool was studied by measuring the spinal monosynaptic reflex responses of soleus muscle to paired stimuli in psychiatric patients and controls. Patients showed significant alterations in the recovery of excitability when compared with normal volunteers. Specifically, the value for the peak of \"secondary facilitation\" was reduced in 5 of 8 chronic schizophrenic patients, while the following trough in the recovery cycle was reduced in 9 of 18 acutely schizophrenic patients. Drug effects were studied in 10 patients. Phenothiazine antipsychotic medication tended to enhance recovery of excitability. Patients of all types showed alterations of excitability. The altered excitability may relfect one aspect of a widespread abnormality of CNS function or may be a specific response to a supraspinal defect in neurophysiological activity in psychotic patients.", "contents": "Motoneuron excitability in psychiatric patients. The excitability at the alpha-motoneuron pool was studied by measuring the spinal monosynaptic reflex responses of soleus muscle to paired stimuli in psychiatric patients and controls. Patients showed significant alterations in the recovery of excitability when compared with normal volunteers. Specifically, the value for the peak of \"secondary facilitation\" was reduced in 5 of 8 chronic schizophrenic patients, while the following trough in the recovery cycle was reduced in 9 of 18 acutely schizophrenic patients. Drug effects were studied in 10 patients. Phenothiazine antipsychotic medication tended to enhance recovery of excitability. Patients of all types showed alterations of excitability. The altered excitability may relfect one aspect of a widespread abnormality of CNS function or may be a specific response to a supraspinal defect in neurophysiological activity in psychotic patients."}
{"id": "PMID:196696", "title": "Thrombin decreases platelet cyclic AMP in the absence of prostaglandin synthesis.", "content": "Cyclic AMP first decreased in wahed platelets after the addition of 0.1 IU thrombin/ml and then increased progressively. Platelets pre-incubated with acetylsalicylic acid showed only a decrease of cyclic AMP upon addition of thrombin. Furthermore, two patients  with defective prostaglandin synthesis had always reduced cyclic AMP whether their platelets were pre-incubated with acetylsalicylic acid or not. Thus, if prostaglandin synthesis is inhibited the level of cyclic AMP decreased and did not increase with time.", "contents": "Thrombin decreases platelet cyclic AMP in the absence of prostaglandin synthesis. Cyclic AMP first decreased in wahed platelets after the addition of 0.1 IU thrombin/ml and then increased progressively. Platelets pre-incubated with acetylsalicylic acid showed only a decrease of cyclic AMP upon addition of thrombin. Furthermore, two patients  with defective prostaglandin synthesis had always reduced cyclic AMP whether their platelets were pre-incubated with acetylsalicylic acid or not. Thus, if prostaglandin synthesis is inhibited the level of cyclic AMP decreased and did not increase with time."}
{"id": "PMID:196697", "title": "Phosphorylation of rhodopsin as a possible mechanism of adaptation.", "content": "Light-induced phosphorylation of rhodopsin has been extensively studied by a number of investigators from a biochemical point of view. However, little is known about the physiological function of this reaction. The slow rates measured for phosphorylation and dephosphorylation suggest that it may be involved in visual adaptation rather than in excitation. This paper presents biochemical data obtained from phosphorylation experiments in isolated photoreceptor membranes as well as in the physiological system of whole retinas and living animals. An attempt is made to compare the phosphorylation reaction with visual adaptation hypotheses taken from the electrophysiological literature. Finally, effects of cyclic nucleotide metabolism on the sensitivity of photoreceptors are presented and discussed.", "contents": "Phosphorylation of rhodopsin as a possible mechanism of adaptation. Light-induced phosphorylation of rhodopsin has been extensively studied by a number of investigators from a biochemical point of view. However, little is known about the physiological function of this reaction. The slow rates measured for phosphorylation and dephosphorylation suggest that it may be involved in visual adaptation rather than in excitation. This paper presents biochemical data obtained from phosphorylation experiments in isolated photoreceptor membranes as well as in the physiological system of whole retinas and living animals. An attempt is made to compare the phosphorylation reaction with visual adaptation hypotheses taken from the electrophysiological literature. Finally, effects of cyclic nucleotide metabolism on the sensitivity of photoreceptors are presented and discussed."}
{"id": "PMID:196700", "title": "The natural history of aminopterin-induced embryopathy.", "content": "A boy whose mother ingested aminopterin to induce abortion and who has the characteristic anomalies caused by fetal exposure to this drug, has been followed for 12.75 yr. Despite short stature, his growth velocity is normal, and both normal endocrine studies and a radiologic bone age, retarded consistently between 2.25 and 3.0 yr, allow a predicted adult height of over 150 cm. Intelligence testing has shown a rise in full scale IQ on the Wechsler Intelligence Scale from 64 to 80 with performance increasing from 70 to 92. Psychologic assessment suggests potential for self-support in adult years.", "contents": "The natural history of aminopterin-induced embryopathy. A boy whose mother ingested aminopterin to induce abortion and who has the characteristic anomalies caused by fetal exposure to this drug, has been followed for 12.75 yr. Despite short stature, his growth velocity is normal, and both normal endocrine studies and a radiologic bone age, retarded consistently between 2.25 and 3.0 yr, allow a predicted adult height of over 150 cm. Intelligence testing has shown a rise in full scale IQ on the Wechsler Intelligence Scale from 64 to 80 with performance increasing from 70 to 92. Psychologic assessment suggests potential for self-support in adult years."}
{"id": "PMID:196701", "title": "[Changes in the electric activity of the cerebral cortex in poisoning caused by Cl. perfringens toxin type A].", "content": "The electrical activity of the cerebral cortex was recorded in cats under mild nembutal anesthesia (15-20 mg/kg of body weight) during the development of Cl. perfringens, type A, toxin poisoning (the toxin was injected intramuscularly in a dose of 100 MLD per kg of body weight). Two phases of the changes in the electrical activity of the cerebral cortex were noted. The first phase was attended by the desynchronization of the electrical activity, persistence of the induced potentials and of the reaction of the rhythm reconstruction to the rhythmic light stimulus. No desynchronization occurred under conditions of preliminary section of the midbrain (on the mesencephalic preparation), this indicating the involvement of the reticular formation into the pathological process and pointing to its role in the desynchronization effect. A profound depression of the electrical activity of the brain, depression of induced potentials and disturbance of the reaction of the rhythm reconstruction occurred during the second phase.", "contents": "[Changes in the electric activity of the cerebral cortex in poisoning caused by Cl. perfringens toxin type A]. The electrical activity of the cerebral cortex was recorded in cats under mild nembutal anesthesia (15-20 mg/kg of body weight) during the development of Cl. perfringens, type A, toxin poisoning (the toxin was injected intramuscularly in a dose of 100 MLD per kg of body weight). Two phases of the changes in the electrical activity of the cerebral cortex were noted. The first phase was attended by the desynchronization of the electrical activity, persistence of the induced potentials and of the reaction of the rhythm reconstruction to the rhythmic light stimulus. No desynchronization occurred under conditions of preliminary section of the midbrain (on the mesencephalic preparation), this indicating the involvement of the reticular formation into the pathological process and pointing to its role in the desynchronization effect. A profound depression of the electrical activity of the brain, depression of induced potentials and disturbance of the reaction of the rhythm reconstruction occurred during the second phase."}
{"id": "PMID:196702", "title": "[Study of the relationship between the glucocorticoid function of the adrenal cortex and blood lipoproteins].", "content": "Single administration of hydrocortisone to rats led to elevation in the blood serum of lipoproteins of very low density; and repeated administration - of lipoproteins of very low density, low density and of high density. Lipoproteins with d less than 1.063 g/ml produced an inhibitory action on the production of steroid hormones by the adrenal glands of rats in vitro.", "contents": "[Study of the relationship between the glucocorticoid function of the adrenal cortex and blood lipoproteins]. Single administration of hydrocortisone to rats led to elevation in the blood serum of lipoproteins of very low density; and repeated administration - of lipoproteins of very low density, low density and of high density. Lipoproteins with d less than 1.063 g/ml produced an inhibitory action on the production of steroid hormones by the adrenal glands of rats in vitro."}
{"id": "PMID:196703", "title": "[Effect of ethyl ether of p-chlorphenoxyisobutyric acid on the glucocorticoid function of the adrenal cortex of guinea pigs].", "content": "In administration to quinea pigs of ethyl-p-chlorophenoxyisobutyrate daily in a dose of 0.2 g/kg per os for 15-26 days decreased the 17-OHCS concentration in the peripheral blood plasma. A fall of the urinary excretion of individual 17-OHCS occurred chiefly at the expense of free unchanged cortisol, tetrahydrocortisol and tetrahydro-11-desoxycortisol. The zona fasciculate displays the abundance of the sudanophilic material. A test with ACTH demonstrated that the present functional reserves of the adrenal cortex failed to change under the effect of the preparation. The content of NEFA decreased in the blood serum; as to cholesterol level - it reamined unchanged. Possible mechanisms of the action of the preparation and prospects of its use for the treatment of hypercorticism are discussed.", "contents": "[Effect of ethyl ether of p-chlorphenoxyisobutyric acid on the glucocorticoid function of the adrenal cortex of guinea pigs]. In administration to quinea pigs of ethyl-p-chlorophenoxyisobutyrate daily in a dose of 0.2 g/kg per os for 15-26 days decreased the 17-OHCS concentration in the peripheral blood plasma. A fall of the urinary excretion of individual 17-OHCS occurred chiefly at the expense of free unchanged cortisol, tetrahydrocortisol and tetrahydro-11-desoxycortisol. The zona fasciculate displays the abundance of the sudanophilic material. A test with ACTH demonstrated that the present functional reserves of the adrenal cortex failed to change under the effect of the preparation. The content of NEFA decreased in the blood serum; as to cholesterol level - it reamined unchanged. Possible mechanisms of the action of the preparation and prospects of its use for the treatment of hypercorticism are discussed."}
{"id": "PMID:196704", "title": "[Cytochrome content in the liver of rabbits in chronic carbon tetrachloride poisoning after perenteral administration of exogenous cytochrome C].", "content": "Administration of exogenous cytochrome C to rats poisoned with CCl4 prevented reduction of the cytochrome C content in the homogenates, and of cytochromes a+a3, b and c+c1 in the hepatic mitochondria; it also promoted the normalization of the histostructure of the organ.", "contents": "[Cytochrome content in the liver of rabbits in chronic carbon tetrachloride poisoning after perenteral administration of exogenous cytochrome C]. Administration of exogenous cytochrome C to rats poisoned with CCl4 prevented reduction of the cytochrome C content in the homogenates, and of cytochromes a+a3, b and c+c1 in the hepatic mitochondria; it also promoted the normalization of the histostructure of the organ."}
{"id": "PMID:196705", "title": "[Diurnal rhythm of cell proliferation at the late stages of precancerous changes in the liver induced by ortho-aminoazo-toluene].", "content": "Orthoaminoazotoluol was administered to mice for a period of nine months. Circadian rhythms of mitotic activity and the number of the DNA-synthesizing cells were determined by autoradiography (with the use of 3H-thymidine) at the second (adenomatous nodes) and the third (primary hepatoma) stages of carcinogenesis in the developing tumours and the surrounding liver parenchyma. The listed structures proved to have a single-peak rhythm of mitotic activity with the maximum of mitoses at 4-7 a. m.; the labeled nuclei circadian rhythm was double-peaked with the maximum at 7 p. m. and 4 a. m. The mean 24-hour values of both indices at the second and third stages of hepatocarcinogenesis were much greater than in the surrounding non-tumour tissue of the liver.", "contents": "[Diurnal rhythm of cell proliferation at the late stages of precancerous changes in the liver induced by ortho-aminoazo-toluene]. Orthoaminoazotoluol was administered to mice for a period of nine months. Circadian rhythms of mitotic activity and the number of the DNA-synthesizing cells were determined by autoradiography (with the use of 3H-thymidine) at the second (adenomatous nodes) and the third (primary hepatoma) stages of carcinogenesis in the developing tumours and the surrounding liver parenchyma. The listed structures proved to have a single-peak rhythm of mitotic activity with the maximum of mitoses at 4-7 a. m.; the labeled nuclei circadian rhythm was double-peaked with the maximum at 7 p. m. and 4 a. m. The mean 24-hour values of both indices at the second and third stages of hepatocarcinogenesis were much greater than in the surrounding non-tumour tissue of the liver."}
{"id": "PMID:196706", "title": "[Effect of heat and cold on the amylolytic and invertase activity of the small intestine of growing rats].", "content": "Acute experiments were conducted on ratlings; it was shown that the action of heat (40-41 degrees C), cold (5-6 degrees C), and ACTH injections (4 units per 100 g of body weight) during the first week after birth led to a sharp reduction of the total (alpha-gamma-conditioned) amylolytic and invertase activity of the homogenates and of the portions of the small intestine (turned inside out) of the growing rats. This depressed condition of the intestinal function was revealed directly after the arrest of the action of the unfavourable factors (7-day rats) and persisted for the subsequent two weeks of the animal life.", "contents": "[Effect of heat and cold on the amylolytic and invertase activity of the small intestine of growing rats]. Acute experiments were conducted on ratlings; it was shown that the action of heat (40-41 degrees C), cold (5-6 degrees C), and ACTH injections (4 units per 100 g of body weight) during the first week after birth led to a sharp reduction of the total (alpha-gamma-conditioned) amylolytic and invertase activity of the homogenates and of the portions of the small intestine (turned inside out) of the growing rats. This depressed condition of the intestinal function was revealed directly after the arrest of the action of the unfavourable factors (7-day rats) and persisted for the subsequent two weeks of the animal life."}
{"id": "PMID:196709", "title": "Effects of dibutyryl cyclic adenosine 3',5'-monophosphate and theophylline on the bullfrog sympathetic ganglion cells.", "content": "1 Effects of dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) and theophylline on bullfrog sympathetic ganglion cells were examined in order to test the hypothesis that cyclic AMP is essential for the generation of slow inhibitory postsynaptic potentials (i.p.s.ps) in these cells. 2 In the absence or presence of theophylline, dibutyryl cyclic AMP did not hyperpolarize but rather tended to depolarize ganglia that were hyperpolarized by adrenaline. 3 Theophylline augmented neither the P-potential (slow i.p.s.p.) nor adrenaline-induced hyperpolarization. 4 Thus, cyclic AMP does not seem to be essential for the generation of the slow i.p.s.p., at least in amphibian sympathetic ganglion cells.", "contents": "Effects of dibutyryl cyclic adenosine 3',5'-monophosphate and theophylline on the bullfrog sympathetic ganglion cells. 1 Effects of dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) and theophylline on bullfrog sympathetic ganglion cells were examined in order to test the hypothesis that cyclic AMP is essential for the generation of slow inhibitory postsynaptic potentials (i.p.s.ps) in these cells. 2 In the absence or presence of theophylline, dibutyryl cyclic AMP did not hyperpolarize but rather tended to depolarize ganglia that were hyperpolarized by adrenaline. 3 Theophylline augmented neither the P-potential (slow i.p.s.p.) nor adrenaline-induced hyperpolarization. 4 Thus, cyclic AMP does not seem to be essential for the generation of the slow i.p.s.p., at least in amphibian sympathetic ganglion cells."}
{"id": "PMID:196711", "title": "Gas gangrene and related infection: classification, clinical features and aetiology, management and mortality. A report of 88 cases.", "content": "The clinical features of gas gangrene and related infection seen in 88 patients over a 10-year period are described. It is suggested that clostridial infection could be simply classified as either 'gas-forming' or 'non-gas-forming'. The gas-forming group represents the more severe form of infection. Non-clostridial gas gangrene may present in a variety of forms. The anaerobic streptococcus was the organism most frequently responsible, but these cases were indistinguishable from clostridial infection on clinical grounds. The treatment of gas gangrene in this series of patients is reported. Emphasis is laid on the importance of adequate prophylaxis with penicillin in patients at risk. The value of antibiotics in established infection remains equivocal. The evidence supporting the value of hyperbaric oxygen therapy is assessed and an attempt made to quantify the response to this treatment. Benefit was apparent in only a proportion of patients. A favourable response indicated clostridial infection and guaranteed immediate survival. Extensive debridement or amputation is unnecessary in this group. No response following hyperbaric oxygen therapy indicated widespread mixed clostridial and non-clostridial infection, or infection due to organisms other than clostridia. Urgent and extensive debridement and amputation remain the predominant measures in this group.", "contents": "Gas gangrene and related infection: classification, clinical features and aetiology, management and mortality. A report of 88 cases. The clinical features of gas gangrene and related infection seen in 88 patients over a 10-year period are described. It is suggested that clostridial infection could be simply classified as either 'gas-forming' or 'non-gas-forming'. The gas-forming group represents the more severe form of infection. Non-clostridial gas gangrene may present in a variety of forms. The anaerobic streptococcus was the organism most frequently responsible, but these cases were indistinguishable from clostridial infection on clinical grounds. The treatment of gas gangrene in this series of patients is reported. Emphasis is laid on the importance of adequate prophylaxis with penicillin in patients at risk. The value of antibiotics in established infection remains equivocal. The evidence supporting the value of hyperbaric oxygen therapy is assessed and an attempt made to quantify the response to this treatment. Benefit was apparent in only a proportion of patients. A favourable response indicated clostridial infection and guaranteed immediate survival. Extensive debridement or amputation is unnecessary in this group. No response following hyperbaric oxygen therapy indicated widespread mixed clostridial and non-clostridial infection, or infection due to organisms other than clostridia. Urgent and extensive debridement and amputation remain the predominant measures in this group."}
{"id": "PMID:196712", "title": "Successful treatment of early cancer of the liver and portal hypertension in patients presenting with bleeding oesophageal varices.", "content": "A small hepatoma was diagnosed by selective arteriography in 2 patients admitted for treatment of bleeding oesophageal varices. In both cases, hepatoma and variceal lesions were successfully treated. In the first case, left gastric vena caval shunt and local excision of the hepatoma were performed. In the second case, distal splenorenal shunt and local excision of the tumour were carried out. Although a combination of hepatoma and oesophageal varices may be an embarrassing problem, both lesions can be remedied provided that hepatoma is diagnosed at an early stage. It is stressed that arteriography is of value in assessment.", "contents": "Successful treatment of early cancer of the liver and portal hypertension in patients presenting with bleeding oesophageal varices. A small hepatoma was diagnosed by selective arteriography in 2 patients admitted for treatment of bleeding oesophageal varices. In both cases, hepatoma and variceal lesions were successfully treated. In the first case, left gastric vena caval shunt and local excision of the hepatoma were performed. In the second case, distal splenorenal shunt and local excision of the tumour were carried out. Although a combination of hepatoma and oesophageal varices may be an embarrassing problem, both lesions can be remedied provided that hepatoma is diagnosed at an early stage. It is stressed that arteriography is of value in assessment."}
{"id": "PMID:196713", "title": "Dopamine-sensitive adenylate cyclase within laminae of the olfactory tubercle.", "content": "There are three histological laminae within the rat olfactory tubercle: plexiform, pyramidal and polymorphic. We have assayed dopamine-sensitive adenylate cyclase in homogenates of frozen sections cut parallel to these laminae. Consecutive sections were cut of alternating thickness, 16 micron and 100 micron. The 16 micron sections were stained with toluidine blue to ascertain the depth and orientation of each section. The 100 micron sections were homogenized and assayed for dopamine-sensitive adenylate cyclase. Substantial levels of dopamine-sensitive adenylate cyclase were found within all three laminae. The results suggest that the enzyme occurs in cell processes, including dendrites, of the plexiform layer, and they are consistent with the localization of dopamine-sensitive adenylate cyclase in the pyramidal cells.", "contents": "Dopamine-sensitive adenylate cyclase within laminae of the olfactory tubercle. There are three histological laminae within the rat olfactory tubercle: plexiform, pyramidal and polymorphic. We have assayed dopamine-sensitive adenylate cyclase in homogenates of frozen sections cut parallel to these laminae. Consecutive sections were cut of alternating thickness, 16 micron and 100 micron. The 16 micron sections were stained with toluidine blue to ascertain the depth and orientation of each section. The 100 micron sections were homogenized and assayed for dopamine-sensitive adenylate cyclase. Substantial levels of dopamine-sensitive adenylate cyclase were found within all three laminae. The results suggest that the enzyme occurs in cell processes, including dendrites, of the plexiform layer, and they are consistent with the localization of dopamine-sensitive adenylate cyclase in the pyramidal cells."}
{"id": "PMID:196714", "title": "[3H]dihydroergocryptine binding in rat brain.", "content": "[3H]dihydroergocryptine (DHE) appears to bind to alpha-adrenergic receptor sites in rabbit uterine membranes. We have characterized the binding of [3H]DHE to membranes prepared from rat cerebral cortex. alpha-Adrenergic agents were less potent and dopamine and serotonin, more potent, in displacing brain DHE binding than in uterus. Furthermore brain DHE binding sites demonstrated less stereospecificity for catecholamines than sites in uterus. Dopamine displaced DHE binding with about the same potency in cerebellar and cerebral cortical membranes, but was 10 times as potent in displacing DHE binding in the striatum. The binding of [3H]DHE in brain is complex and differs significantly from the rabbit uterus. There are two possible explanations for this discrepancy. [3H]DHE may bind a single site in brain with properties differing from known peripheral adrenergic receptors or DHE may bind to multiple sites in brain, sites which may or may not represent other neurotransmitter receptors.", "contents": "[3H]dihydroergocryptine binding in rat brain. [3H]dihydroergocryptine (DHE) appears to bind to alpha-adrenergic receptor sites in rabbit uterine membranes. We have characterized the binding of [3H]DHE to membranes prepared from rat cerebral cortex. alpha-Adrenergic agents were less potent and dopamine and serotonin, more potent, in displacing brain DHE binding than in uterus. Furthermore brain DHE binding sites demonstrated less stereospecificity for catecholamines than sites in uterus. Dopamine displaced DHE binding with about the same potency in cerebellar and cerebral cortical membranes, but was 10 times as potent in displacing DHE binding in the striatum. The binding of [3H]DHE in brain is complex and differs significantly from the rabbit uterus. There are two possible explanations for this discrepancy. [3H]DHE may bind a single site in brain with properties differing from known peripheral adrenergic receptors or DHE may bind to multiple sites in brain, sites which may or may not represent other neurotransmitter receptors."}
{"id": "PMID:196716", "title": "Suppression of radioiodide accumulation by the thyroids and oocytes of Japanese quail with perrhenate.", "content": "Japanese quail, 50% inhibition of the 3-h accumulation of 131I occurred with 2.0 micromol KReO4, 2.2 micromol KClO4 and 13 micromol KSCN for the growing oocytes, 1.7, 1.9 and 4.2 micromol for the thyroids of females and 0.20, 0.47 and 5.6 micromol for the thyroids of males. 2. KReO4 inhibition failed after 24 h in males and 36 h in females. 3. Maxima at 6 h in the 131I curves for the plasma, the livers and the testes of KReO4-treated birds were attributed to retention of 131I in the plasma.", "contents": "Suppression of radioiodide accumulation by the thyroids and oocytes of Japanese quail with perrhenate. Japanese quail, 50% inhibition of the 3-h accumulation of 131I occurred with 2.0 micromol KReO4, 2.2 micromol KClO4 and 13 micromol KSCN for the growing oocytes, 1.7, 1.9 and 4.2 micromol for the thyroids of females and 0.20, 0.47 and 5.6 micromol for the thyroids of males. 2. KReO4 inhibition failed after 24 h in males and 36 h in females. 3. Maxima at 6 h in the 131I curves for the plasma, the livers and the testes of KReO4-treated birds were attributed to retention of 131I in the plasma."}
{"id": "PMID:196717", "title": "[Sodium diethyldithiocarbamate is a stimulating agent of immunity].", "content": "A single dose of DTC was administered, in a dose-range from 0.6 mg/kg to 25 mg/kg, to mice immunized with 10(8) sheep red cells (SRC). All doses strongly enhanced plaque-forming spleen cell (PFC) responses, when given either 18 h before, simultaneously to, 6 h or 24 h after SRC immunization. However, the higher levels of immunostimulation were attained by DTC doses above 5 mg/kg. DTC-induced immunopotentiation was not accompanied by untoward effects, such as acute toxicity, splenomegalia or modifcations in counts of viable spleen lymphocytes.", "contents": "[Sodium diethyldithiocarbamate is a stimulating agent of immunity]. A single dose of DTC was administered, in a dose-range from 0.6 mg/kg to 25 mg/kg, to mice immunized with 10(8) sheep red cells (SRC). All doses strongly enhanced plaque-forming spleen cell (PFC) responses, when given either 18 h before, simultaneously to, 6 h or 24 h after SRC immunization. However, the higher levels of immunostimulation were attained by DTC doses above 5 mg/kg. DTC-induced immunopotentiation was not accompanied by untoward effects, such as acute toxicity, splenomegalia or modifcations in counts of viable spleen lymphocytes."}
{"id": "PMID:196718", "title": "[Demonstration by immunofluorescence of adenohyphysis corticotropin and melanotropin cells in Erythrocebus patas, Cercopithecus aethiops and Papio hamadryas].", "content": "Using antibodies against synthetic corticotropic hormones (1-24 ACTH and 17-39 ACTH), and melanotropic hormones (alpha-MSH and beta-MSH), it is possible to identify corticotropic and melanotropic cells in the adenohypophysis of three species of monkeys : Erythrocebus patas, Cercopithecus aethiops and Papio hamadryas. The corticotropic cells are numerous in the anterior lobe in both the adult and infant male and female monkeys of these three species. The intermediate lobe reacts with antibodies against ACTH and also with antibodies against the two MSH. In the anterior lobe, the corticotropic cells react also with anti-beta MSH antibody but not with the anti-alpha MSH antibody.", "contents": "[Demonstration by immunofluorescence of adenohyphysis corticotropin and melanotropin cells in Erythrocebus patas, Cercopithecus aethiops and Papio hamadryas]. Using antibodies against synthetic corticotropic hormones (1-24 ACTH and 17-39 ACTH), and melanotropic hormones (alpha-MSH and beta-MSH), it is possible to identify corticotropic and melanotropic cells in the adenohypophysis of three species of monkeys : Erythrocebus patas, Cercopithecus aethiops and Papio hamadryas. The corticotropic cells are numerous in the anterior lobe in both the adult and infant male and female monkeys of these three species. The intermediate lobe reacts with antibodies against ACTH and also with antibodies against the two MSH. In the anterior lobe, the corticotropic cells react also with anti-beta MSH antibody but not with the anti-alpha MSH antibody."}
{"id": "PMID:196715", "title": "Diencephalic sites responsive to prostaglandin E2 facilitation of sexual receptivity in estrogen-primed ovariectomized rats.", "content": "Crystalline prostaglandin E2 (PGE2) induced high levels of sexual receptivity when stereotaxically implanted into the antirior-bala hypothalamic and preoptic regions of estrogen-primed, ovariectomized rats. Anterior- as well as medial basal hypothalamic implants of PGE2 induced a significant elevation of rectal body temperature, but had no effect on open-field activity scores. The possibility that PGE2 exerts its facilitatory effects upon sexual receptivity via an LHRH mechanism is discussed.", "contents": "Diencephalic sites responsive to prostaglandin E2 facilitation of sexual receptivity in estrogen-primed ovariectomized rats. Crystalline prostaglandin E2 (PGE2) induced high levels of sexual receptivity when stereotaxically implanted into the antirior-bala hypothalamic and preoptic regions of estrogen-primed, ovariectomized rats. Anterior- as well as medial basal hypothalamic implants of PGE2 induced a significant elevation of rectal body temperature, but had no effect on open-field activity scores. The possibility that PGE2 exerts its facilitatory effects upon sexual receptivity via an LHRH mechanism is discussed."}
{"id": "PMID:196719", "title": "Initial studies on the crystallinity of the mineral fraction and ash content of isolated human and bovine osteons differing in their degree of calcification.", "content": "Several groups containing 10--15 isolated osteons differing in their degree of maturity were analysed. Samples were isolated from undecalcified human and bovine bone sections. The crystallinity coefficient, defined as the ratio of the number of radiation-induced paramagnetic defects in the crystalline lattice of hydroxyapatite to the total ash content, was calculated. The results were compared with measurements performed on fragments of total cortical bone, primary periosteal bone, and inner circumferential lamellar bone. The results show a higher crystallinity of fully calcified osteons as compared with that found at the initial stage of calcification. No differences in the ash content were observed between human osteons, from different stages of calcification evaluated morphologically and by X-ray absorption. These differences were evident when bovine osteons differing in their stage of calcification were compared. Human fully calcified osteons contain 60% ash and their crystallinity coefficient is 52.1. Human osteons at the initial stage of calcification contain 57% ash and their crystallinity coefficient is 40.6. The same parameters for fully calcified bovine osteons and for bovine osteons at the initial stage of calcification are 59% ash, 62.6 crystallinity coefficient and 46% ash, 43.0 crystallinity coefficient, respectively.", "contents": "Initial studies on the crystallinity of the mineral fraction and ash content of isolated human and bovine osteons differing in their degree of calcification. Several groups containing 10--15 isolated osteons differing in their degree of maturity were analysed. Samples were isolated from undecalcified human and bovine bone sections. The crystallinity coefficient, defined as the ratio of the number of radiation-induced paramagnetic defects in the crystalline lattice of hydroxyapatite to the total ash content, was calculated. The results were compared with measurements performed on fragments of total cortical bone, primary periosteal bone, and inner circumferential lamellar bone. The results show a higher crystallinity of fully calcified osteons as compared with that found at the initial stage of calcification. No differences in the ash content were observed between human osteons, from different stages of calcification evaluated morphologically and by X-ray absorption. These differences were evident when bovine osteons differing in their stage of calcification were compared. Human fully calcified osteons contain 60% ash and their crystallinity coefficient is 52.1. Human osteons at the initial stage of calcification contain 57% ash and their crystallinity coefficient is 40.6. The same parameters for fully calcified bovine osteons and for bovine osteons at the initial stage of calcification are 59% ash, 62.6 crystallinity coefficient and 46% ash, 43.0 crystallinity coefficient, respectively."}
{"id": "PMID:196720", "title": "The effect of induced metabolic acidosis on vitamin D3 metabolism in rachitic chicks.", "content": "The metabolism of vitamin D3 was studied in 3-week-old, vitamin D deficient chicks, fed since hatching with a diet containing 3% ammonium chloride, 1% calcium, and 0.7% phosphorus. When kidney homogenates were incubated in vitro with [3H]25-(OH)D3, the production of 1,25-(OH)2D3 was reduced by 40% in acidotic birds. During in vivo experiments, after injection of [3H]D3 (1220 pM/bird), the level of 1,25-(OH)2D3 was also reduced in blood plasma, intestine, and tibiae in acidotic chicks as compared with the controls. As a large increase in plasma phosphate was found during acidosis, these results are discussed in relation to the possible role of phosphorus in the control of 1,25-(OH)2D3 synthesis.", "contents": "The effect of induced metabolic acidosis on vitamin D3 metabolism in rachitic chicks. The metabolism of vitamin D3 was studied in 3-week-old, vitamin D deficient chicks, fed since hatching with a diet containing 3% ammonium chloride, 1% calcium, and 0.7% phosphorus. When kidney homogenates were incubated in vitro with [3H]25-(OH)D3, the production of 1,25-(OH)2D3 was reduced by 40% in acidotic birds. During in vivo experiments, after injection of [3H]D3 (1220 pM/bird), the level of 1,25-(OH)2D3 was also reduced in blood plasma, intestine, and tibiae in acidotic chicks as compared with the controls. As a large increase in plasma phosphate was found during acidosis, these results are discussed in relation to the possible role of phosphorus in the control of 1,25-(OH)2D3 synthesis."}
{"id": "PMID:196721", "title": "Neuromuscular block by circulating D-tubocurarine residue following uptake and distribution.", "content": "Serum concentration of d-tubocurarine decreases rapidly after intravenous injection because of uptake and distribution. The circulating residue of an ED 50 dose of d-tubocurarine five minutes after injection will produce no block in a previously unexposed neuromuscular junction. To produce a 50 per cent block with the circulating d-tubocurarine residue in a previously unexposed neuromuscular junction requires an initial injection of 2.5 x ED 50 dose. Five minutes after a dose 5 to 6 times the ED 50, the plasma d-tubocurarine residue is sufficient to produce a total block.", "contents": "Neuromuscular block by circulating D-tubocurarine residue following uptake and distribution. Serum concentration of d-tubocurarine decreases rapidly after intravenous injection because of uptake and distribution. The circulating residue of an ED 50 dose of d-tubocurarine five minutes after injection will produce no block in a previously unexposed neuromuscular junction. To produce a 50 per cent block with the circulating d-tubocurarine residue in a previously unexposed neuromuscular junction requires an initial injection of 2.5 x ED 50 dose. Five minutes after a dose 5 to 6 times the ED 50, the plasma d-tubocurarine residue is sufficient to produce a total block."}
{"id": "PMID:196722", "title": "Regulation of selectivity of CDPcholine: 1,2-diacyl-sn-glycerol cholinephosphotransferase in rat liver microsomes towards different molecular species of 1,2-diacyl-sn-glycerols.", "content": "The suitability of monoenoic, dienoic, tetraenoic, and hexaenoic molecular species of 1,2-diacyl-sn-glycerols as substrates for the CDPcholine: 1,2-diacyl-sn-glycerol cholinephosphotransferase (EC 2.7.8.2) was studied in rat liver microsomes. No statistically significant difference in the rates of phosphatidylcholine synthesis with the various diacylglycerols was found at 0.40 mM, although a moderate discrimination against hexaenoic species relative to monoenoic and dienoic species was observed at 0.25 mM. The addition of palmitoyl-CoA (7.5 micron) significantly enhanced cholinephosphotransferase activity when tetraenoic diacylglycerols were added at 0.25 or 0.40 mM. CDPethanolamine at 24.4 micron was found to inhibit the rates of phophatidylcholine biosynthesis by 54 and 39% with hexaenoic and monoenoic 1,2-diacyl-sn-glycerols, respectively, whereas no significant effects were observed in the case of dienoic and tetraenoic species. These latter findings may partially explain why 1-saturated 2-docosahexaenoyl diacylglycerols are used to a greater extent for phosphatidylethanolamine than for phosphatidylcholine synthesis in rat liver in vivo. The present results also suggest that the selectivity of the cholinephosphotransferase for certain molecular species of 1,2-diacyl-sn-glycerols is a function of diacylglycerol concentration and may be mediated under physiological conditions by substrates for enzymes which compete for common diacylglycerol precursors.", "contents": "Regulation of selectivity of CDPcholine: 1,2-diacyl-sn-glycerol cholinephosphotransferase in rat liver microsomes towards different molecular species of 1,2-diacyl-sn-glycerols. The suitability of monoenoic, dienoic, tetraenoic, and hexaenoic molecular species of 1,2-diacyl-sn-glycerols as substrates for the CDPcholine: 1,2-diacyl-sn-glycerol cholinephosphotransferase (EC 2.7.8.2) was studied in rat liver microsomes. No statistically significant difference in the rates of phosphatidylcholine synthesis with the various diacylglycerols was found at 0.40 mM, although a moderate discrimination against hexaenoic species relative to monoenoic and dienoic species was observed at 0.25 mM. The addition of palmitoyl-CoA (7.5 micron) significantly enhanced cholinephosphotransferase activity when tetraenoic diacylglycerols were added at 0.25 or 0.40 mM. CDPethanolamine at 24.4 micron was found to inhibit the rates of phophatidylcholine biosynthesis by 54 and 39% with hexaenoic and monoenoic 1,2-diacyl-sn-glycerols, respectively, whereas no significant effects were observed in the case of dienoic and tetraenoic species. These latter findings may partially explain why 1-saturated 2-docosahexaenoyl diacylglycerols are used to a greater extent for phosphatidylethanolamine than for phosphatidylcholine synthesis in rat liver in vivo. The present results also suggest that the selectivity of the cholinephosphotransferase for certain molecular species of 1,2-diacyl-sn-glycerols is a function of diacylglycerol concentration and may be mediated under physiological conditions by substrates for enzymes which compete for common diacylglycerol precursors."}
{"id": "PMID:196724", "title": "A new method for the fractionation of human plasma high density lipoprotein.", "content": "We have devised a new method for the fractionation of human plasma high density lipoprotein (HDL). The HDL was chromatographed on DEAE-agarose columns using a continuous gradient of 0.06--0.15 M NaCl. The elution pattern obtained showed three phases, each with differing peptide composition. Examination of the three subfraction showed that each contained both apoA-I and apo A-II, but in different proportions. Subfraction 1 contained no apo C-II or C-III-1 and only a trace of apo C-III-2, subfraction 2 contained apo C-II and C-III-1 but no C-III-2, while subfraction 3 contained considerable apo C-III-2 with only traces of apo C-II or C-III-1.", "contents": "A new method for the fractionation of human plasma high density lipoprotein. We have devised a new method for the fractionation of human plasma high density lipoprotein (HDL). The HDL was chromatographed on DEAE-agarose columns using a continuous gradient of 0.06--0.15 M NaCl. The elution pattern obtained showed three phases, each with differing peptide composition. Examination of the three subfraction showed that each contained both apoA-I and apo A-II, but in different proportions. Subfraction 1 contained no apo C-II or C-III-1 and only a trace of apo C-III-2, subfraction 2 contained apo C-II and C-III-1 but no C-III-2, while subfraction 3 contained considerable apo C-III-2 with only traces of apo C-II or C-III-1."}
{"id": "PMID:196725", "title": "The oxidation of ferrocytochrome c in nonbinding buffer.", "content": "The apparent equilibrium constant and rate of oxidation was investigated for the reaction of cytochrome c with iron hexacyanide. It was found that if horse heart ferricytochrome c was exposed to ferricyanide (to oxidize traces of reduced protein) the cytochrome subsequently, even after extensive dialysis, had an apparent equilibrium constant different from that of electrodialyzed protein. The effect of ferricyanide ion apparently cannot be removed by ordinary dialysis. The ionic strength dependence of the apparent equilibrium constant and bimolecular oxidation rate constant was measured in the range 1--200 mM using Tris--cacodylate or potassium phosphate buffers at pH 7.0, and electrodialyzed horse heart cytochrome c. The oxidation reaction proceeded very rapidly. Extrapolated to zero ionic strength, kox (approximately 9 X 10(9) M-1 S-1) was about 7% of that calculated for a diffusion-limited reaction. Since the exposed heme edge occupies only the order of 3% of the surface area, electron transfer apparently results at nearly every collision with the active-site region. An effective charge of + 7.8 units was estimated for the oxidation reaction. The rate of oxidation of Pseudomonas aeruginosa c551 was much slower (kox at mu = 0 was the order of 6 X 10(3)), and was not consistent with diffusion-limited kinetics.", "contents": "The oxidation of ferrocytochrome c in nonbinding buffer. The apparent equilibrium constant and rate of oxidation was investigated for the reaction of cytochrome c with iron hexacyanide. It was found that if horse heart ferricytochrome c was exposed to ferricyanide (to oxidize traces of reduced protein) the cytochrome subsequently, even after extensive dialysis, had an apparent equilibrium constant different from that of electrodialyzed protein. The effect of ferricyanide ion apparently cannot be removed by ordinary dialysis. The ionic strength dependence of the apparent equilibrium constant and bimolecular oxidation rate constant was measured in the range 1--200 mM using Tris--cacodylate or potassium phosphate buffers at pH 7.0, and electrodialyzed horse heart cytochrome c. The oxidation reaction proceeded very rapidly. Extrapolated to zero ionic strength, kox (approximately 9 X 10(9) M-1 S-1) was about 7% of that calculated for a diffusion-limited reaction. Since the exposed heme edge occupies only the order of 3% of the surface area, electron transfer apparently results at nearly every collision with the active-site region. An effective charge of + 7.8 units was estimated for the oxidation reaction. The rate of oxidation of Pseudomonas aeruginosa c551 was much slower (kox at mu = 0 was the order of 6 X 10(3)), and was not consistent with diffusion-limited kinetics."}
{"id": "PMID:196726", "title": "Studies on phosphoglyceromutase from chicken breast muscle: chemical modification of lysyl residues.", "content": "To examine the role of lysyl residues in the activity of the enzyme, phosphoglyceromutase (PGM) from chicken breast muscle was chemically modified with trinitrobenzenesulfonate (TNBS) and pyridoxal 5'-phosphate. Trinitrophenylation resulted in modification of about nine lysines per mole of PGM with almost complete activity loss. Substrate (3-PGA) offered some protection to TNBS inactivation but cofactor (2,3-DPGA) did not. Reduction of the Schiff's base complex between pyridoxal 5'-phosphate and PGM gave irreversible inactivation of the enzyme. Inactivation was due to incorporation of 1 mol of pyridoxal 5'-phosphate per mole of PGM dimer through the epsilon-amino group of a lysyl residue. The effect of pyridoxal 5'-phosphate was specific for intact native enzyme and reaction with only one lysine per dimer was not due to induced conformational changes nor to dissociation of the reacted enzyme. 3-PGA prevented much of the reaction with pyridoxal 5'-phosphate with preservation of 70% of the activity and was a competitive inhibitor of the active site directed reagent. Cofactor (2,3-DPGA) acting noncompetitively, reduced the rate at which inactivation occurred with pyridoxal 5'-phosphate. Incorporation of 2,3-[32P]DPGA into PGM irreversibly inactivated with pyridoxal 5'-phosphate and NaBH4 was incomplete indicating hindrance to phosphorylation in the modified enzyme. The results indicate that a lysyl residue is located at or near the active site of PGM and that it is probably involved in the binding of 3-PGA.", "contents": "Studies on phosphoglyceromutase from chicken breast muscle: chemical modification of lysyl residues. To examine the role of lysyl residues in the activity of the enzyme, phosphoglyceromutase (PGM) from chicken breast muscle was chemically modified with trinitrobenzenesulfonate (TNBS) and pyridoxal 5'-phosphate. Trinitrophenylation resulted in modification of about nine lysines per mole of PGM with almost complete activity loss. Substrate (3-PGA) offered some protection to TNBS inactivation but cofactor (2,3-DPGA) did not. Reduction of the Schiff's base complex between pyridoxal 5'-phosphate and PGM gave irreversible inactivation of the enzyme. Inactivation was due to incorporation of 1 mol of pyridoxal 5'-phosphate per mole of PGM dimer through the epsilon-amino group of a lysyl residue. The effect of pyridoxal 5'-phosphate was specific for intact native enzyme and reaction with only one lysine per dimer was not due to induced conformational changes nor to dissociation of the reacted enzyme. 3-PGA prevented much of the reaction with pyridoxal 5'-phosphate with preservation of 70% of the activity and was a competitive inhibitor of the active site directed reagent. Cofactor (2,3-DPGA) acting noncompetitively, reduced the rate at which inactivation occurred with pyridoxal 5'-phosphate. Incorporation of 2,3-[32P]DPGA into PGM irreversibly inactivated with pyridoxal 5'-phosphate and NaBH4 was incomplete indicating hindrance to phosphorylation in the modified enzyme. The results indicate that a lysyl residue is located at or near the active site of PGM and that it is probably involved in the binding of 3-PGA."}
{"id": "PMID:196727", "title": "Some biochemical effects of 4-deoxy-4-fluoro-D-glucose on Escherichia coli.", "content": "The uptake of 4-deoxy-4-fluoro-D-glucose (4FG), without subsequent catabolism, by resting cells of Escherichia coli (ATCC 11775) is 0.06 mg/mg dry weight. In frozen-thawed cells of this organism, 4FG is a substrate for the phosphoenolpyruvate phosphotransferase system with a rate of phosphorylation twice that found for the isomeric 3-deoxy-3-fluoro-D-glucose. 4FG is not a carbon source for growth of this organism and it inhibits the extent of growth of cells in the presence of glucose. The inhibition of growth of E. coli K12 on lactose by 4FG is also observed and this is considered to be consistent with the fact that 4FG is an uncompetitive inhibitor of beta-galactosidase (EC 3.2.1.23) activity and that 4FG or 4-deoxy-4-fluoro-D-glucose-6 phosphate repress beta-galactosidase synthesis. These results support the view that catabolite repression may be produced by compounds which are not necessarily metabolised further than hexose-6-phosphates.", "contents": "Some biochemical effects of 4-deoxy-4-fluoro-D-glucose on Escherichia coli. The uptake of 4-deoxy-4-fluoro-D-glucose (4FG), without subsequent catabolism, by resting cells of Escherichia coli (ATCC 11775) is 0.06 mg/mg dry weight. In frozen-thawed cells of this organism, 4FG is a substrate for the phosphoenolpyruvate phosphotransferase system with a rate of phosphorylation twice that found for the isomeric 3-deoxy-3-fluoro-D-glucose. 4FG is not a carbon source for growth of this organism and it inhibits the extent of growth of cells in the presence of glucose. The inhibition of growth of E. coli K12 on lactose by 4FG is also observed and this is considered to be consistent with the fact that 4FG is an uncompetitive inhibitor of beta-galactosidase (EC 3.2.1.23) activity and that 4FG or 4-deoxy-4-fluoro-D-glucose-6 phosphate repress beta-galactosidase synthesis. These results support the view that catabolite repression may be produced by compounds which are not necessarily metabolised further than hexose-6-phosphates."}
{"id": "PMID:196728", "title": "Estimation of time of divergence from phylogenetic studies.", "content": "Recent studies with comparative data on base sequences of homologous DNA's or amino acid sequences of homologous proteins indicate that simultaneous estimation of phylogenetic structure and time of divergence is often cumbersome and time consuming. On the other hand, when the topology of an evolutionary tree is known, it is shown in this paper that the least squares theory may be applied to obtain simple estimates of the relative time lengths for each segment of the tree under the assumption of uniform random substitutions in each segment. The method is illustrated with amino acid sequence data on various globin molecules and cytochrome c. The evolutionary significance of some of the estimates is also discussed.", "contents": "Estimation of time of divergence from phylogenetic studies. Recent studies with comparative data on base sequences of homologous DNA's or amino acid sequences of homologous proteins indicate that simultaneous estimation of phylogenetic structure and time of divergence is often cumbersome and time consuming. On the other hand, when the topology of an evolutionary tree is known, it is shown in this paper that the least squares theory may be applied to obtain simple estimates of the relative time lengths for each segment of the tree under the assumption of uniform random substitutions in each segment. The method is illustrated with amino acid sequence data on various globin molecules and cytochrome c. The evolutionary significance of some of the estimates is also discussed."}
{"id": "PMID:196729", "title": "A comparison of six methods for the concentration of a porcine enterovirus.", "content": "Single-step concentration of porcine enterovirus strain T80 by adsorption to the polyelectrolyte PE60 gave virus concentration factors of 35- to 88-fold in terms of plaque-forming units, with recovery rates of 22 to 75% of total virus present in the original virus suspension. Concentration by separation in an aqueous polymer two-phase system gave virus concentration factors of 56- to 105-fold and recovery rates of 37 to 107%. In the latter procedure, sodium dextran sulfate appeared to have no effect on plaque numbers, although plaques were sharper and clearer when this substance was incorporated in the overlay. The failure of sonication of virus concentrated by either procedure to increase plaque numbers indicated the absence of virus aggregates in the concentrates. T80 virus was not effectively concentrated by cobalt chloride or polyethylene glycol precipitation or by adsorption to either aluminium hydroxide or calcium hydrogen phosphate.", "contents": "A comparison of six methods for the concentration of a porcine enterovirus. Single-step concentration of porcine enterovirus strain T80 by adsorption to the polyelectrolyte PE60 gave virus concentration factors of 35- to 88-fold in terms of plaque-forming units, with recovery rates of 22 to 75% of total virus present in the original virus suspension. Concentration by separation in an aqueous polymer two-phase system gave virus concentration factors of 56- to 105-fold and recovery rates of 37 to 107%. In the latter procedure, sodium dextran sulfate appeared to have no effect on plaque numbers, although plaques were sharper and clearer when this substance was incorporated in the overlay. The failure of sonication of virus concentrated by either procedure to increase plaque numbers indicated the absence of virus aggregates in the concentrates. T80 virus was not effectively concentrated by cobalt chloride or polyethylene glycol precipitation or by adsorption to either aluminium hydroxide or calcium hydrogen phosphate."}
{"id": "PMID:196730", "title": "The effect of the antiherpesvirus drug 5-methoxymethyl-2'-deoxyuridine on the humoral immune response in vivo.", "content": "5-Methoxymethyl-2'-deoxyuridine (MMUdR), a drug with potent antiviral activity in vitro against Herpes simplex virus, was investigated for its immunosuppressive effects. Doses as high as 2000mg/kg given daily for 9 days were not immunosupporessive as judged by the fact that treated animals produced normal immune responses to sheep erythrocytes, Brucella bacteria, and Herpes simplex virus.", "contents": "The effect of the antiherpesvirus drug 5-methoxymethyl-2'-deoxyuridine on the humoral immune response in vivo. 5-Methoxymethyl-2'-deoxyuridine (MMUdR), a drug with potent antiviral activity in vitro against Herpes simplex virus, was investigated for its immunosuppressive effects. Doses as high as 2000mg/kg given daily for 9 days were not immunosupporessive as judged by the fact that treated animals produced normal immune responses to sheep erythrocytes, Brucella bacteria, and Herpes simplex virus."}
{"id": "PMID:196733", "title": "Elastosis and other stromal reactions in benign and malignant breast tissue: an ultrastructural study.", "content": "The stroma and stromal reaction in normal breast, benign, and malignant breast tissue was studied by electron microscopy. Elastosis is the main stromal response in infiltrating duct and lobular carcinomas. Medullary carcinoma elicits no significant elastosis but intraductal carcinoma has significant local elastosis. Benign conditions such as fibroadenoma and sclerosing adenosis produced no significant elastosis. The high number of elastic fibers and the high microfibril:elastin ratio indicate that most of the elastic fibers are recently secreted, probably by fibroblasts and myofibroblasts. The factors stimulating the increased production of elastic fibers and the prognostic significance of elastosis remain unclear.", "contents": "Elastosis and other stromal reactions in benign and malignant breast tissue: an ultrastructural study. The stroma and stromal reaction in normal breast, benign, and malignant breast tissue was studied by electron microscopy. Elastosis is the main stromal response in infiltrating duct and lobular carcinomas. Medullary carcinoma elicits no significant elastosis but intraductal carcinoma has significant local elastosis. Benign conditions such as fibroadenoma and sclerosing adenosis produced no significant elastosis. The high number of elastic fibers and the high microfibril:elastin ratio indicate that most of the elastic fibers are recently secreted, probably by fibroblasts and myofibroblasts. The factors stimulating the increased production of elastic fibers and the prognostic significance of elastosis remain unclear."}
{"id": "PMID:196735", "title": "Chemotherapy of malignant major salivary gland neoplasms: a 25-year review of M. D. Anderson Hospital experience.", "content": "From 1950 through 1975, 671 patients with malignant major salivary gland neoplasms were referred to M. D. Anderson Hospital and Tumor Institute. Thirty-six patients with advanced local or metastatic disease subsequently underwent 62 evaluable trials with a variety of chemotherapeutic agents, either alone or in combination. Six patients achieved a partial response, with a median duration of 3 months. Ten additional patients had stable disease for 2 or more months. Anthracyclines appeared to be the most effective agents in this study, with three partial responses of six evaluable trials. The longest partial response (10 months) occurred in a patient receiving combination chemotherapy plus BCG immunotherapy. Pulmonary metastases were most commonly responsive to chemotherapy. The median intervals from diagnosis to death or to last follow-up and from initiation of chemotherapy to death or to last follow-up were 30 months and 6 months, respectively. Further therapeutic trials are necessary before response rates to single chemotherapeutic agents or combinations can be accurately assessed. In view of the poor prognosis of patients with recurrent disease, postoperative adjuvant studies with chemoimmunotherapy in patients with a high risk of recurrence are planned.", "contents": "Chemotherapy of malignant major salivary gland neoplasms: a 25-year review of M. D. Anderson Hospital experience. From 1950 through 1975, 671 patients with malignant major salivary gland neoplasms were referred to M. D. Anderson Hospital and Tumor Institute. Thirty-six patients with advanced local or metastatic disease subsequently underwent 62 evaluable trials with a variety of chemotherapeutic agents, either alone or in combination. Six patients achieved a partial response, with a median duration of 3 months. Ten additional patients had stable disease for 2 or more months. Anthracyclines appeared to be the most effective agents in this study, with three partial responses of six evaluable trials. The longest partial response (10 months) occurred in a patient receiving combination chemotherapy plus BCG immunotherapy. Pulmonary metastases were most commonly responsive to chemotherapy. The median intervals from diagnosis to death or to last follow-up and from initiation of chemotherapy to death or to last follow-up were 30 months and 6 months, respectively. Further therapeutic trials are necessary before response rates to single chemotherapeutic agents or combinations can be accurately assessed. In view of the poor prognosis of patients with recurrent disease, postoperative adjuvant studies with chemoimmunotherapy in patients with a high risk of recurrence are planned."}
{"id": "PMID:196736", "title": "Treatment of small cell anaplastic carcinoma of the lung with the oral solution of VP-16-213 (NSC 141540, 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside).", "content": "The semisynthetic podophyllotoxin derivative VP-16-213 (NSC 141540) has been evaluated in a phase II study in patients with small cell anaplastic carcinoma of the lung. The drug was administered as an oral solution, the drinking ampoule, in doses of 100 mg twice a day for 4 days in 30 patients previously treated with intensive combination chemotherapy and for 5 days in 10 untreated patients. The courses were repeated every third week with dose modifications according to individual tolerance. All patients had measurable disease and objective responses were obtained in 20 patients (50%), 15 previously treated (50%) and 5 untreated patients (50%). The median time for response after the start of treatment was 15 days (range 6-42) and the median duration of response was 56 days (range 16-147). Dose-limiting toxicity was principally hematologic, consisting of leukopenia, but gastrointestinal toxicity and alopecia were also observed. The study demonstrated that VP-16-213 administered as an oral solution is highly effective against small cell anaplastic carcinoma of the lung without clinical cross-resistance to CCNU, cyclophosphamide, methotrexate, or vincristine.", "contents": "Treatment of small cell anaplastic carcinoma of the lung with the oral solution of VP-16-213 (NSC 141540, 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside). The semisynthetic podophyllotoxin derivative VP-16-213 (NSC 141540) has been evaluated in a phase II study in patients with small cell anaplastic carcinoma of the lung. The drug was administered as an oral solution, the drinking ampoule, in doses of 100 mg twice a day for 4 days in 30 patients previously treated with intensive combination chemotherapy and for 5 days in 10 untreated patients. The courses were repeated every third week with dose modifications according to individual tolerance. All patients had measurable disease and objective responses were obtained in 20 patients (50%), 15 previously treated (50%) and 5 untreated patients (50%). The median time for response after the start of treatment was 15 days (range 6-42) and the median duration of response was 56 days (range 16-147). Dose-limiting toxicity was principally hematologic, consisting of leukopenia, but gastrointestinal toxicity and alopecia were also observed. The study demonstrated that VP-16-213 administered as an oral solution is highly effective against small cell anaplastic carcinoma of the lung without clinical cross-resistance to CCNU, cyclophosphamide, methotrexate, or vincristine."}
{"id": "PMID:196738", "title": "Soluble membrane antigens of brain tumors. I. Controlled testing for cell-mediated immune responses in a long surviving glioblastoma multiforme patient.", "content": "A patient with glioblastoma multiforme survived 18 years after diagnosis and underwent 20 operations for extracranial metastasis. An immunologic survey of the patient was made over a 1-year-period using in vitro tests of lymphocyte responsiveness and skin tests with control and tumor antigens isolated from autologous and allogenic brain cell membranes. Two tissue-associated soluble cell membrane antigens also present in normal white matter, and two tumor-associated antigens (TAA) produce cell-mediated immune responses in patients with brain tumors. One of these tumor-associated antigens predominates in meningioma cells. In addition some low molecular weight components appeared, which seemed to be unique for the glioblastoma cells from the long-surviving patient.", "contents": "Soluble membrane antigens of brain tumors. I. Controlled testing for cell-mediated immune responses in a long surviving glioblastoma multiforme patient. A patient with glioblastoma multiforme survived 18 years after diagnosis and underwent 20 operations for extracranial metastasis. An immunologic survey of the patient was made over a 1-year-period using in vitro tests of lymphocyte responsiveness and skin tests with control and tumor antigens isolated from autologous and allogenic brain cell membranes. Two tissue-associated soluble cell membrane antigens also present in normal white matter, and two tumor-associated antigens (TAA) produce cell-mediated immune responses in patients with brain tumors. One of these tumor-associated antigens predominates in meningioma cells. In addition some low molecular weight components appeared, which seemed to be unique for the glioblastoma cells from the long-surviving patient."}
{"id": "PMID:196739", "title": "Viral oncolysate in the management of malignant melanoma. I. Preparation of the oncolysate and measurement of immunologic responses.", "content": "Primary explants of human malignant melanoma were utilized in the preparation of oncolysates by Newcastle disease virus. The concentrated lysate, administered parenterally, was employed in an effort to augment antitumor immunologic responses in patients with metastatic melanoma. Observed cellular changes suggested a benefit, but humoral antibody measurements were not impressive.", "contents": "Viral oncolysate in the management of malignant melanoma. I. Preparation of the oncolysate and measurement of immunologic responses. Primary explants of human malignant melanoma were utilized in the preparation of oncolysates by Newcastle disease virus. The concentrated lysate, administered parenterally, was employed in an effort to augment antitumor immunologic responses in patients with metastatic melanoma. Observed cellular changes suggested a benefit, but humoral antibody measurements were not impressive."}
{"id": "PMID:196740", "title": "Viral oncolysate in the management of malignant melanoma. II. Clinical studies.", "content": "Melanoma cell oncolysate, prepared with Newcastle disease virus, was administered as an immunostimulant to 13 patients with metastatic melanoma. The oncolysate was well tolerated. Six treated patients evidenced a decrease in the size of skin nodules or diseased lymph nodes. Visceral lesions were not favorably influenced to any marked degree. One case of fulminating disease showed a change to slow progression and survived a year longer than was otherwise expected. Another patient, whose melanoma could not be controlled by surgery or chemotherapy, has been in complete remission for 2 years. It appears that viral oncolysate might be particularly helpful to patients with early disease.", "contents": "Viral oncolysate in the management of malignant melanoma. II. Clinical studies. Melanoma cell oncolysate, prepared with Newcastle disease virus, was administered as an immunostimulant to 13 patients with metastatic melanoma. The oncolysate was well tolerated. Six treated patients evidenced a decrease in the size of skin nodules or diseased lymph nodes. Visceral lesions were not favorably influenced to any marked degree. One case of fulminating disease showed a change to slow progression and survived a year longer than was otherwise expected. Another patient, whose melanoma could not be controlled by surgery or chemotherapy, has been in complete remission for 2 years. It appears that viral oncolysate might be particularly helpful to patients with early disease."}
{"id": "PMID:196741", "title": "A scanning electron microscopic study of diffuse mesothelioma and some lung carcinomas.", "content": "Seventeen cancers from lung and pleura were studied with scanning, transmission electron, and light microscopy (SEM, TEM and LM). Diffuse mesothelioma mimics bronchioloalveolar carcinoma at LM but shaggy microvilli were found on the cellular surface of the former, and short sprouts densely packed or loosely scattered, on that of the latter. Neolumen formation was found in both. Oat cell carcinoma had a smooth surface with occasional tiny projections and minute surface depressions. The cellular projections of squamous cell carcinoma were quite irregular. Differentiation between diffuse mesothelioma and bronchioloalveolar carcinoma appears feasible with SEM in tissue appropriately fixed either with formaldehyde or glutaraldehyde. The role SEM can play in diagnostic pathology is yet to be explored.", "contents": "A scanning electron microscopic study of diffuse mesothelioma and some lung carcinomas. Seventeen cancers from lung and pleura were studied with scanning, transmission electron, and light microscopy (SEM, TEM and LM). Diffuse mesothelioma mimics bronchioloalveolar carcinoma at LM but shaggy microvilli were found on the cellular surface of the former, and short sprouts densely packed or loosely scattered, on that of the latter. Neolumen formation was found in both. Oat cell carcinoma had a smooth surface with occasional tiny projections and minute surface depressions. The cellular projections of squamous cell carcinoma were quite irregular. Differentiation between diffuse mesothelioma and bronchioloalveolar carcinoma appears feasible with SEM in tissue appropriately fixed either with formaldehyde or glutaraldehyde. The role SEM can play in diagnostic pathology is yet to be explored."}
{"id": "PMID:196742", "title": "Ultrastructure of atypical fibroxanthoma.", "content": "Electron microscopic examination of an atypical fibroxanthoma (AFX) confirmed the fibrohistiocytic nature of this lesion. Ultrastructural evidence suggested a transition from fibroblasts to large giant cells with intermediate forms exhibiting features of both. A comparison of AFX ultrastructural features to those of other similar neoplasms suggested a possible relationship to malignant fibrous histiocytoma. As diagnosed by light microscopy, AFX probably represents a spectrum of neoplasms; this concept is discussed. It is urged, when possible, that electron microscopy be performed on lesions diagnosed as atypical fibroxanthoma since ultrastructure studies represent the most valid basis on which a correct diagnosis can be made.", "contents": "Ultrastructure of atypical fibroxanthoma. Electron microscopic examination of an atypical fibroxanthoma (AFX) confirmed the fibrohistiocytic nature of this lesion. Ultrastructural evidence suggested a transition from fibroblasts to large giant cells with intermediate forms exhibiting features of both. A comparison of AFX ultrastructural features to those of other similar neoplasms suggested a possible relationship to malignant fibrous histiocytoma. As diagnosed by light microscopy, AFX probably represents a spectrum of neoplasms; this concept is discussed. It is urged, when possible, that electron microscopy be performed on lesions diagnosed as atypical fibroxanthoma since ultrastructure studies represent the most valid basis on which a correct diagnosis can be made."}
{"id": "PMID:196743", "title": "Ectopic ACTH, prostatic oat cell carcinoma, and marked hypernatremia.", "content": "Locally recurrent, poorly differentiated carcinoma of the prostate was associated with hypokalemic alkalosis, marked hypernatremia, diabetes mellitus of recent onset, and hyperosmolar syndrome. These findings, with mild hypertension, in the absence of clinical features of Cushing's syndrome, suggested an ectopic ACTH syndrome. Plasma ACTH and cortisol levels were markedly elevated, and failed to suppress in response to either low or high-dose dexamethazone administration. The patient's condition deteriorated rapidly. Autopsy findings included carcinoma extensively infiltrating the prostate with extension to the urinary bladder, and metastases confined to the pelvic nodes and soft tissues. The adrenal glands weighed 23 g and showed diffuse hyperplasia. Extract of the prostatic tumor was analyzed for ACTH and showed approximately 40 times normal plasma levels (or about 4,010 pg/g of tissue); ultrastructural features showed secretory granules consistent with ACTH content of the tumor cells. Such cells were positive when stained for ACTH by peroxidase-tagged immunochemical methods. The case fulfills all established criteria for relating excess corticosteroid production and nonpituitary tumors.", "contents": "Ectopic ACTH, prostatic oat cell carcinoma, and marked hypernatremia. Locally recurrent, poorly differentiated carcinoma of the prostate was associated with hypokalemic alkalosis, marked hypernatremia, diabetes mellitus of recent onset, and hyperosmolar syndrome. These findings, with mild hypertension, in the absence of clinical features of Cushing's syndrome, suggested an ectopic ACTH syndrome. Plasma ACTH and cortisol levels were markedly elevated, and failed to suppress in response to either low or high-dose dexamethazone administration. The patient's condition deteriorated rapidly. Autopsy findings included carcinoma extensively infiltrating the prostate with extension to the urinary bladder, and metastases confined to the pelvic nodes and soft tissues. The adrenal glands weighed 23 g and showed diffuse hyperplasia. Extract of the prostatic tumor was analyzed for ACTH and showed approximately 40 times normal plasma levels (or about 4,010 pg/g of tissue); ultrastructural features showed secretory granules consistent with ACTH content of the tumor cells. Such cells were positive when stained for ACTH by peroxidase-tagged immunochemical methods. The case fulfills all established criteria for relating excess corticosteroid production and nonpituitary tumors."}
{"id": "PMID:196744", "title": "Cystic partially differentiated nephroblastoma: a clinicopathologic entity in the spectrum of infantile renal neoplasia.", "content": "Three cases of cystic partially differentiated nephroblastoma (CPDN) are presented and ten cases from literature are reviewed. CPDN has been designated by various terms; it is a cystic encapsulated tumor occurring before 2 years of age. Cysts are lined by epithelium; septa of the cysts show a mixture of partially differentiated and undifferentiated metanephrogenic blastema. This histologic feature distinguishes CPDN from multilocular cyst of kidney. In seven cases simple nephrectomy, and in remaining cases nephrectomy with radiation and/or chemotherapy, had been the treatment. The disease-free interval ranged from 5 to 72 months, without reports of recurrence or metastasis. CPDN appears to take a benign course and simple nephrectomy seems to be the treatemtn of choice. However, in view of the possibility of recurrence as shown in rare instances by congenital mesoblastic nephroma, another less aggressive lesion in the spectrum of infantile renal neoplasia, regular follow up is recommended.", "contents": "Cystic partially differentiated nephroblastoma: a clinicopathologic entity in the spectrum of infantile renal neoplasia. Three cases of cystic partially differentiated nephroblastoma (CPDN) are presented and ten cases from literature are reviewed. CPDN has been designated by various terms; it is a cystic encapsulated tumor occurring before 2 years of age. Cysts are lined by epithelium; septa of the cysts show a mixture of partially differentiated and undifferentiated metanephrogenic blastema. This histologic feature distinguishes CPDN from multilocular cyst of kidney. In seven cases simple nephrectomy, and in remaining cases nephrectomy with radiation and/or chemotherapy, had been the treatment. The disease-free interval ranged from 5 to 72 months, without reports of recurrence or metastasis. CPDN appears to take a benign course and simple nephrectomy seems to be the treatemtn of choice. However, in view of the possibility of recurrence as shown in rare instances by congenital mesoblastic nephroma, another less aggressive lesion in the spectrum of infantile renal neoplasia, regular follow up is recommended."}
{"id": "PMID:196745", "title": "Histologic types of bronchogenic cancer in relation to different conditions of radiation exposure.", "content": "The rish of lung cancer among the uranium miner study group was found to be not only connected with the increase in frequency of different histologic types of lung cancer, but mainly with the increase of small cell undifferentiated and epidermoid type frequencies. It appears that the frequency of these two major histologic types may be influenced by the level of cumulated radiation exposure and by the time course of cumulation of exposure in a different way. These findings, in agreement wit recent data of Archer et al., eliminate the former assumption that radiation can induce an elevated frequency of only one histologic type of lung cancer.", "contents": "Histologic types of bronchogenic cancer in relation to different conditions of radiation exposure. The rish of lung cancer among the uranium miner study group was found to be not only connected with the increase in frequency of different histologic types of lung cancer, but mainly with the increase of small cell undifferentiated and epidermoid type frequencies. It appears that the frequency of these two major histologic types may be influenced by the level of cumulated radiation exposure and by the time course of cumulation of exposure in a different way. These findings, in agreement wit recent data of Archer et al., eliminate the former assumption that radiation can induce an elevated frequency of only one histologic type of lung cancer."}
{"id": "PMID:196746", "title": "Hepatocellular carcinoma in a woman on long-term oral contraceptives.", "content": "A 32-year-old woman on oral contraceptives for 12 years developed a hepatocellular carcinoma, which resulted in death 15 months after initial diagnosis. The possible association between this malignant hepatic tumor and the long-term use of oral contraceptives is reviewed.", "contents": "Hepatocellular carcinoma in a woman on long-term oral contraceptives. A 32-year-old woman on oral contraceptives for 12 years developed a hepatocellular carcinoma, which resulted in death 15 months after initial diagnosis. The possible association between this malignant hepatic tumor and the long-term use of oral contraceptives is reviewed."}
{"id": "PMID:196747", "title": "Mixed germ cell-sex cord stroma tumor of the ovary associated with isosexual precocious puberty in a normal girl.", "content": "A case of mixed germ cell-sex cord stroma tumor occurring in a normal 8-year-old girl with 46XX karyotype is reported. The child presented with evidence of isosexual precocious puberty 3 years prior to the excision of the tumor. Although the tumor was known to be present at least 2 years prior to its excision and weighed more than 1 kg, there was no evidence of involvement of the adjacent organs or metastases at the time of excision. The contralateral ovary was normal. The endocrine activity abated following the excision of the tumor and the patient is well and free of disease 2 years after the operation. The literature concerning this entity is discussed and reviewed.", "contents": "Mixed germ cell-sex cord stroma tumor of the ovary associated with isosexual precocious puberty in a normal girl. A case of mixed germ cell-sex cord stroma tumor occurring in a normal 8-year-old girl with 46XX karyotype is reported. The child presented with evidence of isosexual precocious puberty 3 years prior to the excision of the tumor. Although the tumor was known to be present at least 2 years prior to its excision and weighed more than 1 kg, there was no evidence of involvement of the adjacent organs or metastases at the time of excision. The contralateral ovary was normal. The endocrine activity abated following the excision of the tumor and the patient is well and free of disease 2 years after the operation. The literature concerning this entity is discussed and reviewed."}
{"id": "PMID:196748", "title": "A lack of correlation between 'T' antigen and any particular human chromosome in hybrids made between SV40 transformed human fibroblasts and mouse LMTK cells.", "content": "Lines of hybrid cells were established by fusion of mouse LMTK- cells with SV40 transformed human fibroblasts. The lines were examined for the presence of SV40 'T' antigen and the human chromosomes they carried identified by Giemsa banding. No significant correlation could be found between any particular human chromosome and the presence of SV40 virus.", "contents": "A lack of correlation between 'T' antigen and any particular human chromosome in hybrids made between SV40 transformed human fibroblasts and mouse LMTK cells. Lines of hybrid cells were established by fusion of mouse LMTK- cells with SV40 transformed human fibroblasts. The lines were examined for the presence of SV40 'T' antigen and the human chromosomes they carried identified by Giemsa banding. No significant correlation could be found between any particular human chromosome and the presence of SV40 virus."}
{"id": "PMID:196749", "title": "Correlation of bacterial mutagenicity and hamster cell transformation with tumorigenicity induced by 2,4-toluenediamine.", "content": "In the presence of rat liver microsome enzymes, 2,4-toluenediamine (TDA) was mutagenic for several tester strains of Salmonella typhimurium. TDA induced morphological transformation in an in vitro carcinogenesis system using secondary culture target cells prepared from cryopreserved primary Syrian hamster embryo cells. These results now correlate bacterial mutagenicity and in vitro morphological transformation with the reported tumorigenicity of this compound.", "contents": "Correlation of bacterial mutagenicity and hamster cell transformation with tumorigenicity induced by 2,4-toluenediamine. In the presence of rat liver microsome enzymes, 2,4-toluenediamine (TDA) was mutagenic for several tester strains of Salmonella typhimurium. TDA induced morphological transformation in an in vitro carcinogenesis system using secondary culture target cells prepared from cryopreserved primary Syrian hamster embryo cells. These results now correlate bacterial mutagenicity and in vitro morphological transformation with the reported tumorigenicity of this compound."}
{"id": "PMID:196750", "title": "C-type virus particles in the transplantable mouse bladder tumour FCB grown in vitro.", "content": "Electron microscopic studies were made on an in vitro cultured cell line obtained from the FCB transplantable murine bladder tumour. The cells exhibited a loss of differentiation compared with solid tumour and the presence of C-type virus particles, many in the process of budding. The possible relation of this virus to murine bladder carcinogenesis is discussed.", "contents": "C-type virus particles in the transplantable mouse bladder tumour FCB grown in vitro. Electron microscopic studies were made on an in vitro cultured cell line obtained from the FCB transplantable murine bladder tumour. The cells exhibited a loss of differentiation compared with solid tumour and the presence of C-type virus particles, many in the process of budding. The possible relation of this virus to murine bladder carcinogenesis is discussed."}
{"id": "PMID:196751", "title": "Spontaneous and induced patterns of the Epstein-Barr virus (EBV) cycle in a new set of somatic cell hybrids.", "content": "A somatic cell hybrid line and its subclones obtained by fusing two Burkitt lymphoma lines (Raji and Namalwa) were examined for the expression of EBV-specific antigens both spontaneously and after induction. The hybrids retained spontaneous early antigen (EA) production at the level characteristic of Raji. Similarly the more permissive Raji pattern dominated the induction of EA by IUDR treatment or P3HR-1 virus superinfection. These findings accord with our previous results on independently derived Raji/Namalwa hybrids. Virus capsid antigen was induced in the hybrids by P3HR-1 virus superinfection though at a lower level than in the Raji parental cell.", "contents": "Spontaneous and induced patterns of the Epstein-Barr virus (EBV) cycle in a new set of somatic cell hybrids. A somatic cell hybrid line and its subclones obtained by fusing two Burkitt lymphoma lines (Raji and Namalwa) were examined for the expression of EBV-specific antigens both spontaneously and after induction. The hybrids retained spontaneous early antigen (EA) production at the level characteristic of Raji. Similarly the more permissive Raji pattern dominated the induction of EA by IUDR treatment or P3HR-1 virus superinfection. These findings accord with our previous results on independently derived Raji/Namalwa hybrids. Virus capsid antigen was induced in the hybrids by P3HR-1 virus superinfection though at a lower level than in the Raji parental cell."}
{"id": "PMID:196752", "title": "Effect of the radioprotective drugs MEA, DMSO, and WR-2721 on tumor control and skin tolerance in the rat.", "content": "Mercaptoethylamine (MEA), dimethylsulfoxide (DMSO), and S-2-(3-aminopropylamino)ethylphosphorothioate (WR-2721) were tested for their protective effects against single and fractionated doses of 250 kv X-rays. Acute and late skin reactions and control of the BA-1112 rhabdomyosarcoma were examined in protected and unprotected WAG/Rij rats. All drugs protected skin in both single and fractionated treatment regimens, with MEA giving the most protection and DMSO the least. DMSO and WR-2721 protected tumors against single doses of radiation, and all three drugs tested protected tumors against fractionated irradiation. As a result, only single-fraction treatments of MEA-protected animals showed therapeutically favorable differential protection.", "contents": "Effect of the radioprotective drugs MEA, DMSO, and WR-2721 on tumor control and skin tolerance in the rat. Mercaptoethylamine (MEA), dimethylsulfoxide (DMSO), and S-2-(3-aminopropylamino)ethylphosphorothioate (WR-2721) were tested for their protective effects against single and fractionated doses of 250 kv X-rays. Acute and late skin reactions and control of the BA-1112 rhabdomyosarcoma were examined in protected and unprotected WAG/Rij rats. All drugs protected skin in both single and fractionated treatment regimens, with MEA giving the most protection and DMSO the least. DMSO and WR-2721 protected tumors against single doses of radiation, and all three drugs tested protected tumors against fractionated irradiation. As a result, only single-fraction treatments of MEA-protected animals showed therapeutically favorable differential protection."}
{"id": "PMID:196755", "title": "Collagen metabolism in experimental cardiac hypertrophy in the rat and the effect of digitoxin treatment.", "content": "It is generally agreed that cardiac hypertrophy is accompanied by the hyperplasia of connective tissue cells. In the present work, collagen metabolism was studied in the heart of nondigitalised and digitalised rats after the constriction of the aorta. The activity of prolyl hydroxylase was maximally increased 2 days after the operation. The incorporation of proline into collagen hydroxyproline increased without any increase in the specific radioactivity of free intracellular proline, the peak labelling of collagen occurring at 4 days. Although the treatment of the rats with digitoxin prevented the development of cardiac hypertrophy and an increase in collagen labelling, an increase in the activity of prolyl hydroxylase was observed. The intracellular free proline pool and its specific radioactivity were significantly lower in digitalised rats as compared with non-digitalised rats. The results indicate that constriction of the aorta is accompanied by an activation of connective tissue cells leading to increased synthesis of collagen. However, digitoxin treatment can prevent the increase in collagen labelling, possibly by inhibiting the amino acid transport, but it is unable to remove the stimulus for hypertrophy.", "contents": "Collagen metabolism in experimental cardiac hypertrophy in the rat and the effect of digitoxin treatment. It is generally agreed that cardiac hypertrophy is accompanied by the hyperplasia of connective tissue cells. In the present work, collagen metabolism was studied in the heart of nondigitalised and digitalised rats after the constriction of the aorta. The activity of prolyl hydroxylase was maximally increased 2 days after the operation. The incorporation of proline into collagen hydroxyproline increased without any increase in the specific radioactivity of free intracellular proline, the peak labelling of collagen occurring at 4 days. Although the treatment of the rats with digitoxin prevented the development of cardiac hypertrophy and an increase in collagen labelling, an increase in the activity of prolyl hydroxylase was observed. The intracellular free proline pool and its specific radioactivity were significantly lower in digitalised rats as compared with non-digitalised rats. The results indicate that constriction of the aorta is accompanied by an activation of connective tissue cells leading to increased synthesis of collagen. However, digitoxin treatment can prevent the increase in collagen labelling, possibly by inhibiting the amino acid transport, but it is unable to remove the stimulus for hypertrophy."}
{"id": "PMID:196757", "title": "Analysis of VSV mutant with attenuated cytopathogenicity: mutation in viral function, P, for inhibition of protein synthesis.", "content": "T1026, a ts mutant of VSV which is much less cytopathogenic than its parent, HR, and which can establish persistent infection under certain conditions, is a double mutant. In addition to its ts mutation in the virion RNA polymerase, T1026 has a second non-ts mutation in a viral function termed \"P\". This function is responsible for the inhibition of total protein synthesis in infected cells and acts chiefly at the level of translational initiation. In some cell systems, the inhibition of protein synthesis produced by P appears to be selective for cellular protein synthesis, whereas in other cell systems, both cellular and viral protein synthesis are inhibited. T1026 and its ts revertants are phenotypically P- -that is, cells infected with them show total protein synthesis rates equal to or greater than uninfected cells, while synthesizing viral proteins at the same or even greater rates than HR-infected cells. The P- mutation is correlated with failure to increase plaque size after 2-3 days of incubation. Since viral mutants obtained from persistently infected cultures in a variety of systems appear to be double mutants with a ts mutation in the virion RNA polymerase and a small plaque marker, we suggest that T1026 could represent a model for such mutants.", "contents": "Analysis of VSV mutant with attenuated cytopathogenicity: mutation in viral function, P, for inhibition of protein synthesis. T1026, a ts mutant of VSV which is much less cytopathogenic than its parent, HR, and which can establish persistent infection under certain conditions, is a double mutant. In addition to its ts mutation in the virion RNA polymerase, T1026 has a second non-ts mutation in a viral function termed \"P\". This function is responsible for the inhibition of total protein synthesis in infected cells and acts chiefly at the level of translational initiation. In some cell systems, the inhibition of protein synthesis produced by P appears to be selective for cellular protein synthesis, whereas in other cell systems, both cellular and viral protein synthesis are inhibited. T1026 and its ts revertants are phenotypically P- -that is, cells infected with them show total protein synthesis rates equal to or greater than uninfected cells, while synthesizing viral proteins at the same or even greater rates than HR-infected cells. The P- mutation is correlated with failure to increase plaque size after 2-3 days of incubation. Since viral mutants obtained from persistently infected cultures in a variety of systems appear to be double mutants with a ts mutation in the virion RNA polymerase and a small plaque marker, we suggest that T1026 could represent a model for such mutants."}
{"id": "PMID:196762", "title": "The early region of SV40 DNA may have more than one gene.", "content": "The nucleotide sequence of 70 base pairs (bp) around 0.545 map units (Alu I C and B junction) of the genome from the single Eco RI cleavage site within SV40 DNA is presented. The mRNA transcribed from the early strand template from this stretch contains two copies of the nonsense triplet UAA in each of the three reading frames. Thus at least 25% of the early region of SV40 DNA does not code for the SV40 \"A\" protein, and the viral contribution to events in the lytic cycle and transformation may be more complex than is generally appreciated.", "contents": "The early region of SV40 DNA may have more than one gene. The nucleotide sequence of 70 base pairs (bp) around 0.545 map units (Alu I C and B junction) of the genome from the single Eco RI cleavage site within SV40 DNA is presented. The mRNA transcribed from the early strand template from this stretch contains two copies of the nonsense triplet UAA in each of the three reading frames. Thus at least 25% of the early region of SV40 DNA does not code for the SV40 \"A\" protein, and the viral contribution to events in the lytic cycle and transformation may be more complex than is generally appreciated."}
{"id": "PMID:196764", "title": "Initiation points for DNA replication in nontransformed and simian virus 40-transformed Chinese hamster lung cells.", "content": "Randomly growing Chinese hamster lung cells were pulse-labeled with 3H-thymidine, and the replicating forks of individual DNA fibers were visualized by autoradiography. When grown in complete medium, wild-type SV40-transformed cells had more forks per unit length of DNA than nontransformed cells. In isoleucine-depleted medium, wild-type SV40-transformed cells had fewer forks per unit length than those few nontransformed cells (1-3% of the population) which continued DNA replication. Cells transformed by a tsA mutant of SV40 when grown at the permissive temperature had more forks per unit length in complete medium and fewer forks per unit length in depleted medium than nontransformed cells, but when grown at the restrictive temperature, the tsA-transformed cells behaved like nontransformed cells.", "contents": "Initiation points for DNA replication in nontransformed and simian virus 40-transformed Chinese hamster lung cells. Randomly growing Chinese hamster lung cells were pulse-labeled with 3H-thymidine, and the replicating forks of individual DNA fibers were visualized by autoradiography. When grown in complete medium, wild-type SV40-transformed cells had more forks per unit length of DNA than nontransformed cells. In isoleucine-depleted medium, wild-type SV40-transformed cells had fewer forks per unit length than those few nontransformed cells (1-3% of the population) which continued DNA replication. Cells transformed by a tsA mutant of SV40 when grown at the permissive temperature had more forks per unit length in complete medium and fewer forks per unit length in depleted medium than nontransformed cells, but when grown at the restrictive temperature, the tsA-transformed cells behaved like nontransformed cells."}
{"id": "PMID:196765", "title": "Transformation of chicken embryo retinal melanoblasts by a temperature-sensitive mutant of Rous sarcoma virus.", "content": "Retinal melanoblasts were transformed by a temperature-sensitive mutant of Rous sarcoma virus (ts-RSV). At the permissive temperature for transformation, the cells cease melanin synthesis, degrade their melanosomes and release much of their accumulated melanin into the medium. At the nonpermissive temperature, the cells assume an epithelioid morphology, actively synthesize melanin and become difficult to distinguish from normal uninfected control cultures. Both the transformed phenotype and the differentiated cell phenotype are temperature-dependent. Infected retinal melanoblasts which are incubated at the nonpermissive temperature and which accumulate a large amount of melanin are unable to transform in response to a temperature shift; instead, the cells degenerate and die. Retinal melanoblasts can be infected by subgroups A, B, C and D of RSV; however, their level of susceptibility to infection is about 1/40 compared to fibroblasts. Cultures infected by ts-RSV produce virus at both temperatures, suggesting that cell phenotype does not regulate virus synthesis.", "contents": "Transformation of chicken embryo retinal melanoblasts by a temperature-sensitive mutant of Rous sarcoma virus. Retinal melanoblasts were transformed by a temperature-sensitive mutant of Rous sarcoma virus (ts-RSV). At the permissive temperature for transformation, the cells cease melanin synthesis, degrade their melanosomes and release much of their accumulated melanin into the medium. At the nonpermissive temperature, the cells assume an epithelioid morphology, actively synthesize melanin and become difficult to distinguish from normal uninfected control cultures. Both the transformed phenotype and the differentiated cell phenotype are temperature-dependent. Infected retinal melanoblasts which are incubated at the nonpermissive temperature and which accumulate a large amount of melanin are unable to transform in response to a temperature shift; instead, the cells degenerate and die. Retinal melanoblasts can be infected by subgroups A, B, C and D of RSV; however, their level of susceptibility to infection is about 1/40 compared to fibroblasts. Cultures infected by ts-RSV produce virus at both temperatures, suggesting that cell phenotype does not regulate virus synthesis."}
{"id": "PMID:196766", "title": "Transformation of chondroblasts by Rous sarcoma virus and synthesis of the sulfated proteoglycan matrix.", "content": "The presence of the extracellular matrix synthesized by chondroblasts provides a barrier to virus penetration. Chondroblasts can be infected and transformed following treatment with proteolytic enzymes. Using a temperature-sensitive transformation mutant of Rous sarcoma virus and rearing the cells at permissive temperature, we demonstrate that transformed chondroblasts stop synthesizing their cell-unique sulfated proteoglycan. If such transformed chondroblasts are shifted to nonpermissive temperature, the cells reinitiate the synthesis of their cell-unique sulfated proteoglycan.", "contents": "Transformation of chondroblasts by Rous sarcoma virus and synthesis of the sulfated proteoglycan matrix. The presence of the extracellular matrix synthesized by chondroblasts provides a barrier to virus penetration. Chondroblasts can be infected and transformed following treatment with proteolytic enzymes. Using a temperature-sensitive transformation mutant of Rous sarcoma virus and rearing the cells at permissive temperature, we demonstrate that transformed chondroblasts stop synthesizing their cell-unique sulfated proteoglycan. If such transformed chondroblasts are shifted to nonpermissive temperature, the cells reinitiate the synthesis of their cell-unique sulfated proteoglycan."}
{"id": "PMID:196767", "title": "The extensive homology between mRNA sequences of normal and SV40-transformed human fibroblasts.", "content": "The poly(A)-containing messenger RNA of normal diploid fibroblast and SV40-transformed progeny cells are compared by cross-hybridizing cDNA. We find a high degree of homology between the mRNA from normal and transformed cells. Despite imperfections in the procedure, the technique permits the conclusion that, at most, 3% of the mRNA in the transformed cell has sequences not present in the normal parental cell. Furthermore, much of the difference appears to occur in low and intermediate complexity classes of mRNA molecules. Extension homology in the mRNA sequences of disparate cell lines may be a general phenomenon, and even HeLa cell mRNA is nearly identical to that of diploid human fibroblasts.", "contents": "The extensive homology between mRNA sequences of normal and SV40-transformed human fibroblasts. The poly(A)-containing messenger RNA of normal diploid fibroblast and SV40-transformed progeny cells are compared by cross-hybridizing cDNA. We find a high degree of homology between the mRNA from normal and transformed cells. Despite imperfections in the procedure, the technique permits the conclusion that, at most, 3% of the mRNA in the transformed cell has sequences not present in the normal parental cell. Furthermore, much of the difference appears to occur in low and intermediate complexity classes of mRNA molecules. Extension homology in the mRNA sequences of disparate cell lines may be a general phenomenon, and even HeLa cell mRNA is nearly identical to that of diploid human fibroblasts."}
{"id": "PMID:196772", "title": "Dibutyryl cAMP-induced protein changes in differentiating mouse neuroblastoma cells.", "content": "Proteins from mouse neuroblastoma cells treated with dibutyryl adenosine-3',5'-monophosphate (B2cAMP) were analyzed by high resolution, two-dimensional gel electrophoresis. Quantitative changes in proteins and charge modifications of proteins apparently induced B2cAMP were detected by isoelectric focusing. Some proteins appeared to be modified and one protein was increased 7- to 8-fold in cells treated with B2cAMP. Since neuroblastoma cells differentiate when treated with B2cAMP, understanding the protein changes induced by B2cAMP may help to understand cellular differentiation in neural tissue.", "contents": "Dibutyryl cAMP-induced protein changes in differentiating mouse neuroblastoma cells. Proteins from mouse neuroblastoma cells treated with dibutyryl adenosine-3',5'-monophosphate (B2cAMP) were analyzed by high resolution, two-dimensional gel electrophoresis. Quantitative changes in proteins and charge modifications of proteins apparently induced B2cAMP were detected by isoelectric focusing. Some proteins appeared to be modified and one protein was increased 7- to 8-fold in cells treated with B2cAMP. Since neuroblastoma cells differentiate when treated with B2cAMP, understanding the protein changes induced by B2cAMP may help to understand cellular differentiation in neural tissue."}
{"id": "PMID:196775", "title": "Synthesis and micellar formation of spin-labeled lysolecithin.", "content": "A spin-labeled lysolecithin, 1-[12'-(N-oxyl-4\",4\"-dimethyloxazolidine)-stearoyl]-sn-glycero-3-phosphorylcholine, has been synthesized in which the spin is covalently attached to its fatty acyl chain. The electron spin resonance spectra of this lysolecithin is an aqueous solution generally showed sharp three resonance lines superposed on a broad resonance line. Investigation of changes in the signal intensity of these spectra against the concentration of lysolecithin led to the inference that the sharp lines are due to monomers of lysolecithin while the broad one to micelles. The critical micellar concentration was consistent with that evaluated from the spectral shift of a dye. In the electron spin resonance spectra obtained from spin-labeled lysolecithin solutions with various amounts of dimyristoyllecithin, the line width of broad signal arised from micellar spin-labeled lysolecithin broadened as increase of dimyristoyllecithin. The line-broadening thus observed was briefly discussed.", "contents": "Synthesis and micellar formation of spin-labeled lysolecithin. A spin-labeled lysolecithin, 1-[12'-(N-oxyl-4\",4\"-dimethyloxazolidine)-stearoyl]-sn-glycero-3-phosphorylcholine, has been synthesized in which the spin is covalently attached to its fatty acyl chain. The electron spin resonance spectra of this lysolecithin is an aqueous solution generally showed sharp three resonance lines superposed on a broad resonance line. Investigation of changes in the signal intensity of these spectra against the concentration of lysolecithin led to the inference that the sharp lines are due to monomers of lysolecithin while the broad one to micelles. The critical micellar concentration was consistent with that evaluated from the spectral shift of a dye. In the electron spin resonance spectra obtained from spin-labeled lysolecithin solutions with various amounts of dimyristoyllecithin, the line width of broad signal arised from micellar spin-labeled lysolecithin broadened as increase of dimyristoyllecithin. The line-broadening thus observed was briefly discussed."}
{"id": "PMID:196779", "title": "Effect of temperature and relative humidity on variola virus in crusts.", "content": "The viability of variola virus in crusts under different conditions of temperature and relative humidity was studied for 16 weeks. At the ambient temperature of 25.8-26.4 degrees C and 85-90% relative humidity, the virus survived only 8 weeks but at lower temperatures and relative humidities the survival time was considerably prolonged.", "contents": "Effect of temperature and relative humidity on variola virus in crusts. The viability of variola virus in crusts under different conditions of temperature and relative humidity was studied for 16 weeks. At the ambient temperature of 25.8-26.4 degrees C and 85-90% relative humidity, the virus survived only 8 weeks but at lower temperatures and relative humidities the survival time was considerably prolonged."}
{"id": "PMID:196780", "title": "[Cytotoxicity of human T-lymphocytes sensitized by Epstein-Barr virus. Role of HLA antigens at the surface of target cells infected by the virus].", "content": "Peripheral T-lymphocytes from patients with infectious mononucleosis are cytotoxic towards target cells from Epstein-Barr virus-genome carrying human lumphoblastoid lines. Thus, these T-cells appear to be sensitized to viral coded determinants. Daudi cells, that carry EBV-genome, but lack HLA antigens are resistant to specific cytolysis in this model. These results suggest direct HLA involvement in the target structure recognized by birus-sensitized cytolytic T-lymphocytes in human.", "contents": "[Cytotoxicity of human T-lymphocytes sensitized by Epstein-Barr virus. Role of HLA antigens at the surface of target cells infected by the virus]. Peripheral T-lymphocytes from patients with infectious mononucleosis are cytotoxic towards target cells from Epstein-Barr virus-genome carrying human lumphoblastoid lines. Thus, these T-cells appear to be sensitized to viral coded determinants. Daudi cells, that carry EBV-genome, but lack HLA antigens are resistant to specific cytolysis in this model. These results suggest direct HLA involvement in the target structure recognized by birus-sensitized cytolytic T-lymphocytes in human."}
{"id": "PMID:196782", "title": "Formation and properties of lactate dehydrogenase inhibitors in NADH.", "content": "We describe some characteristics of the mode of formation of inhibitors of lactate dehydrogenase from commercial NADH. Inhibitor formation is time- and concentration-dependent and also varies with the commercial source of NADH. At least two inhibitory components can form in concentrated NADH solutions. One of these can be separated from NADH by chromatography on either diethylaminoethyl-celluose or diethylaminoethyl-Sephadex; the second cannot. The NADH-associated inhibitor appeared to be present in each of the three commercial NADH preparations studied. The 260 nm/340 nm absorbance ratio was of no help in locating this inhibitor during chromatography.", "contents": "Formation and properties of lactate dehydrogenase inhibitors in NADH. We describe some characteristics of the mode of formation of inhibitors of lactate dehydrogenase from commercial NADH. Inhibitor formation is time- and concentration-dependent and also varies with the commercial source of NADH. At least two inhibitory components can form in concentrated NADH solutions. One of these can be separated from NADH by chromatography on either diethylaminoethyl-celluose or diethylaminoethyl-Sephadex; the second cannot. The NADH-associated inhibitor appeared to be present in each of the three commercial NADH preparations studied. The 260 nm/340 nm absorbance ratio was of no help in locating this inhibitor during chromatography."}
{"id": "PMID:196783", "title": "Lactate dehydrogenase inhibitors in NADH preparations.", "content": "The presence of a new lactate dehydrogenase inhibitor on the trailing edge of the NADH peak from chromatography on diethylaminoethyl-celluose [Loshon et al., Clin. Chem., this issue] was verified. It was resolved from the NADH by high-performance liquid chromatography on muBondapak C18. When the new inhibitor was present in a reaction mixture to the extent that, of the initial 260-nm absorbance, about 5% was contributed by the inhibitor, the rate of NADH oxidation by lactate dehydrogenase decreased by 65%. The inhibitor absorbs at 260 and 340 nm, and is different from the Strandjord-Clayson inhibitor [J. Lab. Clin. Med. 67, 144 (1966)] by both types of chromatography. Because this new inhibitor has ultraviolet properties similar to those of NADH and chromatographs with the NADH on DEAE-cellulose, the high-performance liquid chromatographic method must be used to ensure its absence in preparations of NADH used for clinical assay.", "contents": "Lactate dehydrogenase inhibitors in NADH preparations. The presence of a new lactate dehydrogenase inhibitor on the trailing edge of the NADH peak from chromatography on diethylaminoethyl-celluose [Loshon et al., Clin. Chem., this issue] was verified. It was resolved from the NADH by high-performance liquid chromatography on muBondapak C18. When the new inhibitor was present in a reaction mixture to the extent that, of the initial 260-nm absorbance, about 5% was contributed by the inhibitor, the rate of NADH oxidation by lactate dehydrogenase decreased by 65%. The inhibitor absorbs at 260 and 340 nm, and is different from the Strandjord-Clayson inhibitor [J. Lab. Clin. Med. 67, 144 (1966)] by both types of chromatography. Because this new inhibitor has ultraviolet properties similar to those of NADH and chromatographs with the NADH on DEAE-cellulose, the high-performance liquid chromatographic method must be used to ensure its absence in preparations of NADH used for clinical assay."}
{"id": "PMID:196784", "title": "A fetal intestinal-type alkaline phosphatase in hepatocellular carcinoma tissue.", "content": "We examined 19 hepatoma tissues for alkaline phosphatase isoenzyme and found that six have both the Kasahara isoenzyme and an alkaline phosphatase with a unique electrophoretic mobility, in addition to the liver-type enzyme. From two of six carcinoma tissues, the abnormal enzyme was partly purified and subjected to a detailed analysis, which clarified that the abnormal enzyme resembled a fetal intestinal alkaline phosphatase in most of its enzymic and immunologic properties and also in properties that reflect enzyme structure. This fetal intestinal-type alkaline phosphatase was not found in 24 specimens of normal liver from adults. The relevance of fetal intestinal-type alkaline phosphatase to Kasahara isoenzyme and adult intestinal alkaline phosphatase is discussed. The fetal and adult intestinal alkaline phosphatases differ in electrophoretic mobility, heat stability, and reactivity with concanavalin A. The adult-type enzyme has two components; only the electrophoretically slower, neuraminidase-resistant one is described here.", "contents": "A fetal intestinal-type alkaline phosphatase in hepatocellular carcinoma tissue. We examined 19 hepatoma tissues for alkaline phosphatase isoenzyme and found that six have both the Kasahara isoenzyme and an alkaline phosphatase with a unique electrophoretic mobility, in addition to the liver-type enzyme. From two of six carcinoma tissues, the abnormal enzyme was partly purified and subjected to a detailed analysis, which clarified that the abnormal enzyme resembled a fetal intestinal alkaline phosphatase in most of its enzymic and immunologic properties and also in properties that reflect enzyme structure. This fetal intestinal-type alkaline phosphatase was not found in 24 specimens of normal liver from adults. The relevance of fetal intestinal-type alkaline phosphatase to Kasahara isoenzyme and adult intestinal alkaline phosphatase is discussed. The fetal and adult intestinal alkaline phosphatases differ in electrophoretic mobility, heat stability, and reactivity with concanavalin A. The adult-type enzyme has two components; only the electrophoretically slower, neuraminidase-resistant one is described here."}
{"id": "PMID:196785", "title": "Improved direct determination of serum cholesterol in low-density lipoproteins with use of polycations.", "content": "The previously described procedure of direct determination of LDL-cholesterol after selective extraction of VLDL and HDL with polycations and a polycation-exchange resin has been improved by using dodecoylated poly(ethyleneimine) instead of poly(ethyleneimine). The acyl derivative has a higher affinity for lipoproteins. Disc-electrophoretic patterns of lipoproteins separated by this procedure correspond to patterns of apolipoproteins in VLDL and HDL, a finding that corroborates the conclusion that the mechanism of the selective binding of certain lipoproteins to lipophilic water-soluble polycations is based on hydrophobic interaction between the polymer and lipids located at the surface of lipoprotein particles. The procedure offers a simple possibility for direct LDL-cholesterol and LDL-triglyceride determination and for the isolation of VLDL and HDL. The mechanism of the reaction has a biochemical correlate in the action of phospholipase A2 on phospholipids.", "contents": "Improved direct determination of serum cholesterol in low-density lipoproteins with use of polycations. The previously described procedure of direct determination of LDL-cholesterol after selective extraction of VLDL and HDL with polycations and a polycation-exchange resin has been improved by using dodecoylated poly(ethyleneimine) instead of poly(ethyleneimine). The acyl derivative has a higher affinity for lipoproteins. Disc-electrophoretic patterns of lipoproteins separated by this procedure correspond to patterns of apolipoproteins in VLDL and HDL, a finding that corroborates the conclusion that the mechanism of the selective binding of certain lipoproteins to lipophilic water-soluble polycations is based on hydrophobic interaction between the polymer and lipids located at the surface of lipoprotein particles. The procedure offers a simple possibility for direct LDL-cholesterol and LDL-triglyceride determination and for the isolation of VLDL and HDL. The mechanism of the reaction has a biochemical correlate in the action of phospholipase A2 on phospholipids."}
{"id": "PMID:196786", "title": "Lactate dehydrogenase isoenzymes linked to beta-lipoproteins and immunoglobulin A.", "content": "A clinically asymptomatic individual had an abnormal electrophoretic pattern for lactate dehydrogenase, seven isoenzyme bands being present. This atypical pattern was a result of an interaction of lactate dehydrogenase with immunoglobulin A and beta-lipoprotein. Lactate dehydrogenase enzymes LD2 and LD3 were the isoenzymes responsible for the formation of the complexes.", "contents": "Lactate dehydrogenase isoenzymes linked to beta-lipoproteins and immunoglobulin A. A clinically asymptomatic individual had an abnormal electrophoretic pattern for lactate dehydrogenase, seven isoenzyme bands being present. This atypical pattern was a result of an interaction of lactate dehydrogenase with immunoglobulin A and beta-lipoprotein. Lactate dehydrogenase enzymes LD2 and LD3 were the isoenzymes responsible for the formation of the complexes."}
{"id": "PMID:196789", "title": "Familial hyper-alpha-lipoproteinaemia. Further studies on serum lipoproteins and some serum enzymes.", "content": "Some new data are given concerning a family whose members are characterized by high levels of alpha-(HDL)-cholesterol. Data from the new members of the family, not previously studied, confirm that the defect is not associated with any cardiac or neurological defect nor with xanthomata. Studies performed to assess the polypeptide composition of HDL of the affected members resulted in completely normal results. The post-heparin lipolytic activity (PHLA), the liver lipase and the lecithin-cholesterol acyltransferase (LCAT) activities also proved to be within the normal limits.", "contents": "Familial hyper-alpha-lipoproteinaemia. Further studies on serum lipoproteins and some serum enzymes. Some new data are given concerning a family whose members are characterized by high levels of alpha-(HDL)-cholesterol. Data from the new members of the family, not previously studied, confirm that the defect is not associated with any cardiac or neurological defect nor with xanthomata. Studies performed to assess the polypeptide composition of HDL of the affected members resulted in completely normal results. The post-heparin lipolytic activity (PHLA), the liver lipase and the lecithin-cholesterol acyltransferase (LCAT) activities also proved to be within the normal limits."}
{"id": "PMID:196790", "title": "The composition of low (LDL) and very low (VLDL) density lipoprotein subfractions in type III hyperlipoproteinaemia: comparison with normal subjects.", "content": "The lipid and protein composition of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) subfractions (Sf greater than 100, 60--100 and 20--60 VLDL and Sf 10.4--20, 5.7--12 and 3.5--6.5 LDL) in six subjects with type III hyperlipoproteinaemia (HLP) was compared to that of 12 normal subjects. In type III HLP all VLDL subfractions contained increased concentrations of cholesterol and triglycerides and were relatively enriched in cholesterol. VLDL of Sf 20--60 also contained and increased concentration of B-protein. The tetramethylurea (TMU) soluble apolipoproteins of the VLDL subfractions were separated by polyacrylamide disc gel electrophoresis. In the subjects with type III HLP the proportion of arginine rich protein (ARP) was increased in all subfractions. The concentrations of cholesterol and triglycerides were increased in the LDL subfraction of Sf 10.4--20 and cholesterol was decreased in LDL of Sf 5.7--12, but the ratios of cholesterol to triglycerides were not significantly different from those in the LDL subfractions of the normal subjects and the protein composition was also similar. These results provide further evidence that in type III HLP abnormalities are not confined to the stage of conversion of VLDL to LDL, but occur throughout the VLDL spectrum.", "contents": "The composition of low (LDL) and very low (VLDL) density lipoprotein subfractions in type III hyperlipoproteinaemia: comparison with normal subjects. The lipid and protein composition of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) subfractions (Sf greater than 100, 60--100 and 20--60 VLDL and Sf 10.4--20, 5.7--12 and 3.5--6.5 LDL) in six subjects with type III hyperlipoproteinaemia (HLP) was compared to that of 12 normal subjects. In type III HLP all VLDL subfractions contained increased concentrations of cholesterol and triglycerides and were relatively enriched in cholesterol. VLDL of Sf 20--60 also contained and increased concentration of B-protein. The tetramethylurea (TMU) soluble apolipoproteins of the VLDL subfractions were separated by polyacrylamide disc gel electrophoresis. In the subjects with type III HLP the proportion of arginine rich protein (ARP) was increased in all subfractions. The concentrations of cholesterol and triglycerides were increased in the LDL subfraction of Sf 10.4--20 and cholesterol was decreased in LDL of Sf 5.7--12, but the ratios of cholesterol to triglycerides were not significantly different from those in the LDL subfractions of the normal subjects and the protein composition was also similar. These results provide further evidence that in type III HLP abnormalities are not confined to the stage of conversion of VLDL to LDL, but occur throughout the VLDL spectrum."}
{"id": "PMID:196791", "title": "Measurement of the apoproteins of human serum lipoproteins by rocket immunoelectrophoresis.", "content": "A method has been developed for assay of apolipoproteins A, B and C in human serum, using rocket immunoelectrophoresis. The technique is reasonably simple, sensitive and precise. The concentrations of apolipoproteins A, B and C in these classes of serum lipoproteins were measured in 116 healthy subjects. Concentrations of apoproteins within very low and low density lipoproteins increased with age but those of high density lipoproteins showed no consistent age trend.", "contents": "Measurement of the apoproteins of human serum lipoproteins by rocket immunoelectrophoresis. A method has been developed for assay of apolipoproteins A, B and C in human serum, using rocket immunoelectrophoresis. The technique is reasonably simple, sensitive and precise. The concentrations of apolipoproteins A, B and C in these classes of serum lipoproteins were measured in 116 healthy subjects. Concentrations of apoproteins within very low and low density lipoproteins increased with age but those of high density lipoproteins showed no consistent age trend."}
{"id": "PMID:196793", "title": "The relationship between thyroid function and the renal response to parathyroid hormone.", "content": "The effect of thyroid status on renal adenosine 3', 5'-cyclic monophosphate (cyclic AMP) metabolism was assessed by measuring the increase in plasma cyclic AMP concentration following the intravenous administration of parathyroid hormone (PTH) to five hypothyroid and six hyperthyroid patients and seven euthyroid control subjects. PTH caused a rapid, transient increase in the concentration of plasma cyclic AMP which was similar in magnitude and time course in the euthyroid and hyperthyroid groups, but reduced in magnitude in the hypothyroid patients. The magnitude of the plasma cyclic AMP response to PTH was positively related to the free thyroxine index. The results suggest that the development of hypothyroidism may impair the renal response to PTH by affecting the turnover of cyclic AMP in the renal cortex.", "contents": "The relationship between thyroid function and the renal response to parathyroid hormone. The effect of thyroid status on renal adenosine 3', 5'-cyclic monophosphate (cyclic AMP) metabolism was assessed by measuring the increase in plasma cyclic AMP concentration following the intravenous administration of parathyroid hormone (PTH) to five hypothyroid and six hyperthyroid patients and seven euthyroid control subjects. PTH caused a rapid, transient increase in the concentration of plasma cyclic AMP which was similar in magnitude and time course in the euthyroid and hyperthyroid groups, but reduced in magnitude in the hypothyroid patients. The magnitude of the plasma cyclic AMP response to PTH was positively related to the free thyroxine index. The results suggest that the development of hypothyroidism may impair the renal response to PTH by affecting the turnover of cyclic AMP in the renal cortex."}
{"id": "PMID:196797", "title": "Diagnostic value of serum bile acids.", "content": "With the development of simplified methods of bile acid analysis, a new era has drawned in the evaluation of hepatobiliary disease. 1. A total serum bile acid particularly in the postprandial periods is more sensitive than either BSP or ICG for the detection of minimal liver disease and will become a useful screening method. 2. The ratio of chenodeoxycholate to cholate in serum together with the total concentration can often distinguish hepatitis and cirrhosis from intrahepatic and extrahepatic cholestasis with normal liver cell parenchyma. However, in practice this is usually of less value than the total serum bile acid level. 3. Changes in serum bile acids throughout a 24 hour cycle reflect the enterohepatic circulation of bile acids and the capacity of the liver to transport them. These patterns are most useful in judging the severity of cholestasis and response to resin therapy. They also provide new insights into the pathophysiology of bile acid metabolism and excretion in different diseases of the liver.", "contents": "Diagnostic value of serum bile acids. With the development of simplified methods of bile acid analysis, a new era has drawned in the evaluation of hepatobiliary disease. 1. A total serum bile acid particularly in the postprandial periods is more sensitive than either BSP or ICG for the detection of minimal liver disease and will become a useful screening method. 2. The ratio of chenodeoxycholate to cholate in serum together with the total concentration can often distinguish hepatitis and cirrhosis from intrahepatic and extrahepatic cholestasis with normal liver cell parenchyma. However, in practice this is usually of less value than the total serum bile acid level. 3. Changes in serum bile acids throughout a 24 hour cycle reflect the enterohepatic circulation of bile acids and the capacity of the liver to transport them. These patterns are most useful in judging the severity of cholestasis and response to resin therapy. They also provide new insights into the pathophysiology of bile acid metabolism and excretion in different diseases of the liver."}
{"id": "PMID:196798", "title": "Phagocytosis of immune complexes by polymorphonuclear leucocytes in patients with Felty's syndrome.", "content": "The possible role of phagocytosis of circulating immune complexes by neutrophils in the production of the neutropenia of Felty's syndrome has been investigated. Normal neutrophils phagocytosed massive inclusions from the sera from twelve of fifteen patients with Felty's syndrome when incubated with these sera. Such inclusions were phagocytosed from only three of fifteen patients with seropositive RA who did not have Felty's syndrome. Normal neutrophils were more effective than patient neutrophils with regard to phagocytosis of inclusions from the patients' serum suggesting a defect in phagocytic function of Felty's neutrophils. The titre of granulocyte-reactive antinuclear antibodies did not appear to be related to the degree of neutropenia. The data suggest that phagocytosis of circulating immune complexes by neutrophils may interfere with the function of these cells in combating infection and also render them susceptible to removal from the circulation thus leading to the development of neutropenia.", "contents": "Phagocytosis of immune complexes by polymorphonuclear leucocytes in patients with Felty's syndrome. The possible role of phagocytosis of circulating immune complexes by neutrophils in the production of the neutropenia of Felty's syndrome has been investigated. Normal neutrophils phagocytosed massive inclusions from the sera from twelve of fifteen patients with Felty's syndrome when incubated with these sera. Such inclusions were phagocytosed from only three of fifteen patients with seropositive RA who did not have Felty's syndrome. Normal neutrophils were more effective than patient neutrophils with regard to phagocytosis of inclusions from the patients' serum suggesting a defect in phagocytic function of Felty's neutrophils. The titre of granulocyte-reactive antinuclear antibodies did not appear to be related to the degree of neutropenia. The data suggest that phagocytosis of circulating immune complexes by neutrophils may interfere with the function of these cells in combating infection and also render them susceptible to removal from the circulation thus leading to the development of neutropenia."}
{"id": "PMID:196799", "title": "The effect of acute and prolonged administration of prednisolone and ACTH on lymphocyte subpopulations.", "content": "The effect of acute and prolonged three week administration of prednisolone and ACTH on the numbers and function of T- and B-lymphocyte subpopulations in patients requiring corticosteroid therapy was studied. Prednisolone caused severe reduction in E-rosette-forming lymphocytes, phytohaemagglutinin response, EAC-rosette-forming lymphocytes and surface-membrane mu-positive B-lymphocytes maximal at 4--6 hr after administration with reversal sometimes to supernormal levels by 24 hr. Prolonged administration resulted in a similar pattern of response. Acute but not prolonged prednisolone administration caused a reduction in the percentage of E-rosette-forming lymphocytes maximal at 4 hr. ACTH caused moderate reduction in these parameters at 4 and 6 hr which remained low at 24 hr after prolonged administration.", "contents": "The effect of acute and prolonged administration of prednisolone and ACTH on lymphocyte subpopulations. The effect of acute and prolonged three week administration of prednisolone and ACTH on the numbers and function of T- and B-lymphocyte subpopulations in patients requiring corticosteroid therapy was studied. Prednisolone caused severe reduction in E-rosette-forming lymphocytes, phytohaemagglutinin response, EAC-rosette-forming lymphocytes and surface-membrane mu-positive B-lymphocytes maximal at 4--6 hr after administration with reversal sometimes to supernormal levels by 24 hr. Prolonged administration resulted in a similar pattern of response. Acute but not prolonged prednisolone administration caused a reduction in the percentage of E-rosette-forming lymphocytes maximal at 4 hr. ACTH caused moderate reduction in these parameters at 4 and 6 hr which remained low at 24 hr after prolonged administration."}
{"id": "PMID:196800", "title": "Antibodies against cytomegalovirus-induced early antigens (CMV-EA) in immunosuppressed renal-allograft recipients.", "content": "Antibodies against cytomegalovirus-specific early antigens (CMV-EA) were followed in sera, obtained from fifteen immunosuppressed renal-allograft recipients. Eight patients (sixty-two sera) showed seroconversion 47--137 days post-transplantation. Five patients (forty sera) with CMV antibodies at the moment of renal implantation all showed CMV-EA antibody rises. Two patients remained seronegative until 4 years after transplantation. Thus, in immunosuppressed patients, antibodies against CMV-EA remained a high titres during many years (4--8 years) after transplantation as distinct from the apparently transient nature in acutely infected previously healthy adults with CMV mononucleosis or post-perfusion syndrome. These results support the view that CMV-EA antibodies reflect an active viral proliferation in the host.", "contents": "Antibodies against cytomegalovirus-induced early antigens (CMV-EA) in immunosuppressed renal-allograft recipients. Antibodies against cytomegalovirus-specific early antigens (CMV-EA) were followed in sera, obtained from fifteen immunosuppressed renal-allograft recipients. Eight patients (sixty-two sera) showed seroconversion 47--137 days post-transplantation. Five patients (forty sera) with CMV antibodies at the moment of renal implantation all showed CMV-EA antibody rises. Two patients remained seronegative until 4 years after transplantation. Thus, in immunosuppressed patients, antibodies against CMV-EA remained a high titres during many years (4--8 years) after transplantation as distinct from the apparently transient nature in acutely infected previously healthy adults with CMV mononucleosis or post-perfusion syndrome. These results support the view that CMV-EA antibodies reflect an active viral proliferation in the host."}
{"id": "PMID:196801", "title": "Antibody-dependent cellular cytotoxicity (ADCC) against Epstein-Barr virus-determined antigens II. Induction of ADCC by FC-FC receptor bridging.", "content": "Four different methods to test antibody-dependent cellular cytotoxicity (ADCC) against Epstein-Barr virus (EBV) determined antigens were analysed. It was found that optimal ADCC was obtained if viral antigens were present during the cytotoxicity reaction and that killing probably was mediated by EBV-related immune-complexes forming Fc-Fc receptor bridges between Fc receptor-bearing effector cells and Fc receptor-bearing target cells. Only lymphoid target cells with a high expression of Fc receptors were found to be susceptible in this particular system.", "contents": "Antibody-dependent cellular cytotoxicity (ADCC) against Epstein-Barr virus-determined antigens II. Induction of ADCC by FC-FC receptor bridging. Four different methods to test antibody-dependent cellular cytotoxicity (ADCC) against Epstein-Barr virus (EBV) determined antigens were analysed. It was found that optimal ADCC was obtained if viral antigens were present during the cytotoxicity reaction and that killing probably was mediated by EBV-related immune-complexes forming Fc-Fc receptor bridges between Fc receptor-bearing effector cells and Fc receptor-bearing target cells. Only lymphoid target cells with a high expression of Fc receptors were found to be susceptible in this particular system."}
{"id": "PMID:196812", "title": "Bilirubin inhibition of protein kinase: its prevention by cyclic AMP.", "content": "The effect of bilirubin on protein kinase activity has been studied. Bilirubin inhibits the binding of cyclic AMP to protein kinase. It also inhibits the phosphorylation of histone. The inhibitory action of bilirubin is competitive, and increased amounts of cyclic AMP relieved the inhibition.", "contents": "Bilirubin inhibition of protein kinase: its prevention by cyclic AMP. The effect of bilirubin on protein kinase activity has been studied. Bilirubin inhibits the binding of cyclic AMP to protein kinase. It also inhibits the phosphorylation of histone. The inhibitory action of bilirubin is competitive, and increased amounts of cyclic AMP relieved the inhibition."}
{"id": "PMID:196813", "title": "Mapping AK1, ACONs, and AK3 to chromosome 9 in man employing and X/9 translocation and somatic cell hybrids.", "content": "The adenylate kinase 1 (AK1), adenylate kinase3 (AK3), and aconitaseS (ACONS) genes have been assigned to chromosome 9 in man by employing an X/9 translocation segregating in man-mouse somatic cell hybrids. Segregation was controlled by taking advantage of the HAT/8-azaguanine selection-counterselection strategy directed at the X-linked HPRT locus. Assignment of AK1 to chromosome 9 has suggested the assignment of the ABO blood-group locus and the nail-patella (Np) locus to 9, since both loci are linked to AK1 by family studies.", "contents": "Mapping AK1, ACONs, and AK3 to chromosome 9 in man employing and X/9 translocation and somatic cell hybrids. The adenylate kinase 1 (AK1), adenylate kinase3 (AK3), and aconitaseS (ACONS) genes have been assigned to chromosome 9 in man by employing an X/9 translocation segregating in man-mouse somatic cell hybrids. Segregation was controlled by taking advantage of the HAT/8-azaguanine selection-counterselection strategy directed at the X-linked HPRT locus. Assignment of AK1 to chromosome 9 has suggested the assignment of the ABO blood-group locus and the nail-patella (Np) locus to 9, since both loci are linked to AK1 by family studies."}
{"id": "PMID:196814", "title": "Synteny of the genes for thymidine kinase and galactokinase in the mouse and their assignment to mouse chromosome 11.", "content": "We have studied the expression of mouse galactokinase in human-mouse somatic cell hybrids segregating mouse chromosomes. Since concordant segregation of the expression of mouse galactokinase and the presence of mouse chromosome 11 were observed in the hybrid clones, we conclude that the gene for mouse galactokinase is located on mouse chromosome 11. We have also investigated the expression of mouse galactokinase in somatic cell hybrids between thymidine kinase-deficient Chinese hamster cells and mouse peritoneal macrophages. The results of this study indicate that the expression of mouse galactokinase and thymidine kinase segregates concordantly, and, therefore, we infer that the gene for mouse thymidine kinase is also located on mouse chromosome 11.", "contents": "Synteny of the genes for thymidine kinase and galactokinase in the mouse and their assignment to mouse chromosome 11. We have studied the expression of mouse galactokinase in human-mouse somatic cell hybrids segregating mouse chromosomes. Since concordant segregation of the expression of mouse galactokinase and the presence of mouse chromosome 11 were observed in the hybrid clones, we conclude that the gene for mouse galactokinase is located on mouse chromosome 11. We have also investigated the expression of mouse galactokinase in somatic cell hybrids between thymidine kinase-deficient Chinese hamster cells and mouse peritoneal macrophages. The results of this study indicate that the expression of mouse galactokinase and thymidine kinase segregates concordantly, and, therefore, we infer that the gene for mouse thymidine kinase is also located on mouse chromosome 11."}
{"id": "PMID:196817", "title": "Search for inhibitors against herpes simplex virus type-I in cell extracts derived from human lymphoblastoid cell lines.", "content": "Cell extracts obtained from KB cells and 5 human lymphoblastoid cell lines including 2 from Burkitt's lymphoma (P3HR-1 and Raji), one each from nasopharyngeal carcinoma (no.223), acute lymphatic leukemia (MOLT-4) and a healthy person (NC-37) were tested for their inhibitory effects on the growth of herpes simplex virus type-1 (HSV-1) in green monkey kidney (GMK) cells by the plaque titration method. The relationship between the production of HSV-1 inhibitors and the degree of Epstein-Barr virus (EBV) genome repression in lymphoblastoid cells were also examined. Among the cell lines used P3HR-1 and no.223 cells produced a few EBV particles, Raji and NC-37 cells contained EBV genomes only, and MOLT-4 as well as KB cells were EBV genome-negative. The results revealed that P3HR-1 cell extract showed a tendency to inhibit HSV-1 growth in GMK cells but the other 4 lymphoblastoid cell lines and KB cells did not produce HSV-1 inhibitors, indicating that EBV genomes governing the formation of EBV structural antigens were not related to the production of HSV-1 growth inhibitors. The extracts from MOLT-4 cells, which are only a T lymphocyte cell line used in this study, stimulated HSV-1 growth in GMK cells significantly.", "contents": "Search for inhibitors against herpes simplex virus type-I in cell extracts derived from human lymphoblastoid cell lines. Cell extracts obtained from KB cells and 5 human lymphoblastoid cell lines including 2 from Burkitt's lymphoma (P3HR-1 and Raji), one each from nasopharyngeal carcinoma (no.223), acute lymphatic leukemia (MOLT-4) and a healthy person (NC-37) were tested for their inhibitory effects on the growth of herpes simplex virus type-1 (HSV-1) in green monkey kidney (GMK) cells by the plaque titration method. The relationship between the production of HSV-1 inhibitors and the degree of Epstein-Barr virus (EBV) genome repression in lymphoblastoid cells were also examined. Among the cell lines used P3HR-1 and no.223 cells produced a few EBV particles, Raji and NC-37 cells contained EBV genomes only, and MOLT-4 as well as KB cells were EBV genome-negative. The results revealed that P3HR-1 cell extract showed a tendency to inhibit HSV-1 growth in GMK cells but the other 4 lymphoblastoid cell lines and KB cells did not produce HSV-1 inhibitors, indicating that EBV genomes governing the formation of EBV structural antigens were not related to the production of HSV-1 growth inhibitors. The extracts from MOLT-4 cells, which are only a T lymphocyte cell line used in this study, stimulated HSV-1 growth in GMK cells significantly."}
{"id": "PMID:196818", "title": "Isolation and identification of Marek's disease virus by fluorescent antibody technique.", "content": "Cell-associated herpesvirus related to Marek's disease (MD) was isolated from the direct culture of kidney cells of naturally infected chickens at Taoyuan or by inoculation of clinical specimens to chick kidney (CK) and chick embryo fibroblast cells. The virus isolates replicated in CK or chick embryo kidney cell cultures were identified to be MD by the fluorescent-antibody technique.", "contents": "Isolation and identification of Marek's disease virus by fluorescent antibody technique. Cell-associated herpesvirus related to Marek's disease (MD) was isolated from the direct culture of kidney cells of naturally infected chickens at Taoyuan or by inoculation of clinical specimens to chick kidney (CK) and chick embryo fibroblast cells. The virus isolates replicated in CK or chick embryo kidney cell cultures were identified to be MD by the fluorescent-antibody technique."}
{"id": "PMID:196824", "title": "[Serum lipids in experimental atherosclerosis in guinea pigs treated with protein hydrolysate].", "content": "The authors carried out studies on 223 male guinea pigs, weighting from 350 to 500 gm, fed with a diet containing 0,3% of cholesterol, disolved in cow butter. A part of the animals were injected with protein hydrolysate every other day for a period of 140 days. The level of serum lipids-total cholesterol, beta-lipoproteins, phospholipids and total lipids was examined. They found significantly higher values in the animals, receiving cholesterol in comparison with the control animals-292.4:84.9; 139.4:59.3; 457.1:241.2; 105.5:62.0 respectively for, beta-lipoproteins, total cholesterol, total lipids and phospholipids. The administration of protein hydrolysate in a dose of 0,5 ml/100 gm of body weight affected favourably fat metabolism. The increase of serum fat-lipid components was less manifested in comparison with the nontreated atherosclerotic animals. The greatest difference was found in beta-lipoproteins (292.4:143.8) and total, lipids (457.1:300.8). Statistically significant difference was established in total cholesterol as well. (139.4:81.9). There was an impression that this effect was due to the protective action of aminoacids of the protein hydrolysate on the normal functions of liver and the favourable effect on the tunover of the administered cholesterol.", "contents": "[Serum lipids in experimental atherosclerosis in guinea pigs treated with protein hydrolysate]. The authors carried out studies on 223 male guinea pigs, weighting from 350 to 500 gm, fed with a diet containing 0,3% of cholesterol, disolved in cow butter. A part of the animals were injected with protein hydrolysate every other day for a period of 140 days. The level of serum lipids-total cholesterol, beta-lipoproteins, phospholipids and total lipids was examined. They found significantly higher values in the animals, receiving cholesterol in comparison with the control animals-292.4:84.9; 139.4:59.3; 457.1:241.2; 105.5:62.0 respectively for, beta-lipoproteins, total cholesterol, total lipids and phospholipids. The administration of protein hydrolysate in a dose of 0,5 ml/100 gm of body weight affected favourably fat metabolism. The increase of serum fat-lipid components was less manifested in comparison with the nontreated atherosclerotic animals. The greatest difference was found in beta-lipoproteins (292.4:143.8) and total, lipids (457.1:300.8). Statistically significant difference was established in total cholesterol as well. (139.4:81.9). There was an impression that this effect was due to the protective action of aminoacids of the protein hydrolysate on the normal functions of liver and the favourable effect on the tunover of the administered cholesterol."}
{"id": "PMID:196826", "title": "An improved bioassay for ACTH determination.", "content": "An improved method for the bioassay of ACTH has been developed using short-term culture of adrenal cell suspensions derived from intact rats. Six separate pools of adrenals were used and cells derived from the same pool were compared after acute dispersion and overnight culture. The ED50, defined as the concentration of ACTH required to produce half maximal steroidogenesis, for cultured cells was 35.4+/-2 pg/ml compared to 240+/-60 pg/ml for cells used immediately after dispersion. The minimum concentrations of ACTH necessary to produce a response significantly above basal levels were 0.98+/-.10 pg/ml and 12.1+/-3 pg/ml respectively. Response characteristics of the cultured cells were highly reproducible. The incubation volume employed in this study was 0.25 ml, so the ED50 expressed as dose of ACTH per tube was actually 8.8 pg for the cultured cells. Such sensitivity provides requisite methodology for the measurement of ACTH under varying physiological conditions.", "contents": "An improved bioassay for ACTH determination. An improved method for the bioassay of ACTH has been developed using short-term culture of adrenal cell suspensions derived from intact rats. Six separate pools of adrenals were used and cells derived from the same pool were compared after acute dispersion and overnight culture. The ED50, defined as the concentration of ACTH required to produce half maximal steroidogenesis, for cultured cells was 35.4+/-2 pg/ml compared to 240+/-60 pg/ml for cells used immediately after dispersion. The minimum concentrations of ACTH necessary to produce a response significantly above basal levels were 0.98+/-.10 pg/ml and 12.1+/-3 pg/ml respectively. Response characteristics of the cultured cells were highly reproducible. The incubation volume employed in this study was 0.25 ml, so the ED50 expressed as dose of ACTH per tube was actually 8.8 pg for the cultured cells. Such sensitivity provides requisite methodology for the measurement of ACTH under varying physiological conditions."}
{"id": "PMID:196827", "title": "Characteristics of thyrotropin binding to bovine thyroid plasma membranes and the influence of human IgG.", "content": "The characteristics of binding of 125I-labeled bovine thyrotropin to bovine thyroid plasma membranes were studied. At pH 7.5, 0 C, specific binding was maximal in 3 hr and was progressively inhibited by Na+, Mg++, Ca++ and (NH4)2 SO4 in concentrations of 25 mM and greater. Affinity constants of l.047 X 10(8)M-1 and 0.57 X 10(6)M-1 were obtained for two binding sites and Hill plots provided a mean slope of 0.86, suggesting negative cooperativity. Addition of 1-thyroxine or 1-triiodothyronine at 0.5 ng to 50 microgram per ml had no significant effect but propylthiouracil (10(-7) to 10(-5)M) and KC104 (10(-7) to 10(-4)M) had biphasic effects, first enhancing and then inhibiting binding. Normal human serum IgG, particularly two fractions (3 and 4) obtained by chromatography on columns of cellulose phosphate, and an alpha-globulin - rich fraction from chromatography of serum proteins on diethylaminoethyl cellulose, inhibited binding at concentrations of 0.5 mg per ml or greater. Thus two possibilities are that normal human serum globulins either compete with thyrotropin for its receptor on thyroid plasma membranes or, in binding to the membranes, cause such perturbation as to affect adversely the conformation of the receptor for thyrotropin.", "contents": "Characteristics of thyrotropin binding to bovine thyroid plasma membranes and the influence of human IgG. The characteristics of binding of 125I-labeled bovine thyrotropin to bovine thyroid plasma membranes were studied. At pH 7.5, 0 C, specific binding was maximal in 3 hr and was progressively inhibited by Na+, Mg++, Ca++ and (NH4)2 SO4 in concentrations of 25 mM and greater. Affinity constants of l.047 X 10(8)M-1 and 0.57 X 10(6)M-1 were obtained for two binding sites and Hill plots provided a mean slope of 0.86, suggesting negative cooperativity. Addition of 1-thyroxine or 1-triiodothyronine at 0.5 ng to 50 microgram per ml had no significant effect but propylthiouracil (10(-7) to 10(-5)M) and KC104 (10(-7) to 10(-4)M) had biphasic effects, first enhancing and then inhibiting binding. Normal human serum IgG, particularly two fractions (3 and 4) obtained by chromatography on columns of cellulose phosphate, and an alpha-globulin - rich fraction from chromatography of serum proteins on diethylaminoethyl cellulose, inhibited binding at concentrations of 0.5 mg per ml or greater. Thus two possibilities are that normal human serum globulins either compete with thyrotropin for its receptor on thyroid plasma membranes or, in binding to the membranes, cause such perturbation as to affect adversely the conformation of the receptor for thyrotropin."}
{"id": "PMID:196831", "title": "Stimulation of corticosteroid biosynthesis by angiotensin I [des-asp1]angiotensin I, angiotensin II and [des-asp1]-angiotensin II in bovine adrenal fasciculata cells.", "content": "The effect of angiotensin I (AI), angiotensin II (AII), [des-asp1]AI, [des-asp1]AII and [des-asp1-arg2]AII on corticosteroid production in isolated fasciculata cells from bovine adrenals has been studied. AII and [des-asp1]AII in concentrations ranging from 10(-9)M to 10(-6)M had a potent stimulatory effect on steroid biosynthesis. The dose-response curves for both peptides were identical. AI was about 3 times less potent than AII and [des-asp1]AII. The effect of AI was not due to its conversion to AII. [Des-asp1]AI was as active as AI. No significant conversion to [des-asp1]AII was observed. [Des-asp1-arg2]AII had only a minimal effect on steroidogenesis. The structural analog [sar1,-ala8]AII inhibited all angiotensins specifically and competitively. The affinity of the cellular binding site was higher for AII and [des-asp1]AII than for [sar1,ala8]ALL, but lower for AI and [des-asp1]AI than for the inhibitor. Combination of submaximal doses of AI and AII resulted in an additive effect on steroid production. By contrast, combination of maximal doses of both peptides had the same effect as AII alone. These data demonstrate a potent steroidogenic activity for AII as well as AI, [des-asp1]AI and [des-asp1]AII in bovine adrenal fasciculata cells. A common receptor site for all four peptides is suggested.", "contents": "Stimulation of corticosteroid biosynthesis by angiotensin I [des-asp1]angiotensin I, angiotensin II and [des-asp1]-angiotensin II in bovine adrenal fasciculata cells. The effect of angiotensin I (AI), angiotensin II (AII), [des-asp1]AI, [des-asp1]AII and [des-asp1-arg2]AII on corticosteroid production in isolated fasciculata cells from bovine adrenals has been studied. AII and [des-asp1]AII in concentrations ranging from 10(-9)M to 10(-6)M had a potent stimulatory effect on steroid biosynthesis. The dose-response curves for both peptides were identical. AI was about 3 times less potent than AII and [des-asp1]AII. The effect of AI was not due to its conversion to AII. [Des-asp1]AI was as active as AI. No significant conversion to [des-asp1]AII was observed. [Des-asp1-arg2]AII had only a minimal effect on steroidogenesis. The structural analog [sar1,-ala8]AII inhibited all angiotensins specifically and competitively. The affinity of the cellular binding site was higher for AII and [des-asp1]AII than for [sar1,ala8]ALL, but lower for AI and [des-asp1]AI than for the inhibitor. Combination of submaximal doses of AI and AII resulted in an additive effect on steroid production. By contrast, combination of maximal doses of both peptides had the same effect as AII alone. These data demonstrate a potent steroidogenic activity for AII as well as AI, [des-asp1]AI and [des-asp1]AII in bovine adrenal fasciculata cells. A common receptor site for all four peptides is suggested."}
{"id": "PMID:196832", "title": "Functional heterogeneity in somatotrophs isolated from the rat anterior pituitary.", "content": "Somatotrophs in suspensions of anterior pituitary cells from adult male rats can be separated into 2 fractions by density gradient centrifugation. In addition to their different densities, somatotrophs in these 2 fractions can be distinguished morphologically by their staining characteristics and ultrastructure. Somatotrophs of lesser density (type I; approximately 1.068 g/cm3) have fewer secretory granules and a more extensive Golgi apparatus than the somatotrophs of greater density (type II; approximately 1.073 g/cm3). Responsiveness of type I and type II cells to secretory agents (i.e., dibutyryl cyclic adenosine monophosphate, somatostatin, thyroxine, and hydrocortisone) was evaluated by GH radioimmunoassay. Type I cells were consistently more responsive (% GH release) than type II cells. During 7 days in culture, type I cells produced  more (approximately 200%) GH than they initially contained, whereas type II cells did not show evidence of increased GH production. Hydrocortisone significantly stimulated GH production in type I, but not type II cells. These results support the hypothesis that at least 2 functionally distinct populations of somatotrophs are present in the anterior pituitary gland of the adult male rat.", "contents": "Functional heterogeneity in somatotrophs isolated from the rat anterior pituitary. Somatotrophs in suspensions of anterior pituitary cells from adult male rats can be separated into 2 fractions by density gradient centrifugation. In addition to their different densities, somatotrophs in these 2 fractions can be distinguished morphologically by their staining characteristics and ultrastructure. Somatotrophs of lesser density (type I; approximately 1.068 g/cm3) have fewer secretory granules and a more extensive Golgi apparatus than the somatotrophs of greater density (type II; approximately 1.073 g/cm3). Responsiveness of type I and type II cells to secretory agents (i.e., dibutyryl cyclic adenosine monophosphate, somatostatin, thyroxine, and hydrocortisone) was evaluated by GH radioimmunoassay. Type I cells were consistently more responsive (% GH release) than type II cells. During 7 days in culture, type I cells produced  more (approximately 200%) GH than they initially contained, whereas type II cells did not show evidence of increased GH production. Hydrocortisone significantly stimulated GH production in type I, but not type II cells. These results support the hypothesis that at least 2 functionally distinct populations of somatotrophs are present in the anterior pituitary gland of the adult male rat."}
{"id": "PMID:196836", "title": "In vivo evidence for the intermediary role of 3',5'-cyclic AMP in parathyroid hormone-induced stimulation of 1alpha,25-dihydroxyvitamin D3 synthesis in rats.", "content": "Teh stimulatory effect of parathyroid hormone (PTH) on renal 1alpha-hydroxylation of 25-hydroxyvitamin D3 (25-OH-D3) was studied in thyro-parathyroidectomized (TPTX), vitamin D-deficient rats into which bovine PTH, theophylline, cAMP or dibutyryl cAMP (dbcAMP) was constantly infused. The accumulation in plasma of 1alpha,25-dihydroxy-vitamin D3 [1alpha,25-(OH)2-D3], produced from 25-OH-D3, was enhanced by infusion of either cAMP (0.9 MUMOL/H) OR DBCAMP (1 mumol/h) to a level similar to the maximum obtained by PTH (i95--7.5 U/h) infusion. A submaximal dose (1 U/h) of PTH caused a similar extent of stimulation, when infused with theophylline. When either 2 mumol/h of cAMP or 7.5 U/h of bovine PTH was infused starting 18 h after TPTX, the accumulation of 1alpha,25-(OH)2-D3 in plasma was similarly restored withing 6 h to the level found in the sham-operated animals. These results strongly support the concept that cAMP plays an important intermediary role in the stimulation of 1alpha,25-(OH)2-D3 production induced by both exogenous and endogenous PTH.", "contents": "In vivo evidence for the intermediary role of 3',5'-cyclic AMP in parathyroid hormone-induced stimulation of 1alpha,25-dihydroxyvitamin D3 synthesis in rats. Teh stimulatory effect of parathyroid hormone (PTH) on renal 1alpha-hydroxylation of 25-hydroxyvitamin D3 (25-OH-D3) was studied in thyro-parathyroidectomized (TPTX), vitamin D-deficient rats into which bovine PTH, theophylline, cAMP or dibutyryl cAMP (dbcAMP) was constantly infused. The accumulation in plasma of 1alpha,25-dihydroxy-vitamin D3 [1alpha,25-(OH)2-D3], produced from 25-OH-D3, was enhanced by infusion of either cAMP (0.9 MUMOL/H) OR DBCAMP (1 mumol/h) to a level similar to the maximum obtained by PTH (i95--7.5 U/h) infusion. A submaximal dose (1 U/h) of PTH caused a similar extent of stimulation, when infused with theophylline. When either 2 mumol/h of cAMP or 7.5 U/h of bovine PTH was infused starting 18 h after TPTX, the accumulation of 1alpha,25-(OH)2-D3 in plasma was similarly restored withing 6 h to the level found in the sham-operated animals. These results strongly support the concept that cAMP plays an important intermediary role in the stimulation of 1alpha,25-(OH)2-D3 production induced by both exogenous and endogenous PTH."}
{"id": "PMID:196837", "title": "Solubilization of a growth hormone-specific receptor from rabbit liver.", "content": "Membrane preparations from rabbit liver, known to possess GH-specific binding sites, have been solubilized with Triton X-100 and the binding characteristics of [125I]-human GH (hGH) and [125I]-bovine GH (bGH) subsequently studied. Specific binding of the hGH and bGH by the solubilized preparation was demonstrated of bound and free hormone by either polyethylene glycol precipitation or by Sephadex G-100 chromatography. Binding of hGH was both rapid and reversible and was displaced only by other growth hormones (bovine and ovine) and not by lactogenic hormones (ovine and human prolactins, human placental lactogen). As shown by Scatchard analysis specific binding of [125I]-bGH exhibited a lower binding affinity and capacity than did [125I]-hGH. Overall, the characteristics of the binding reaction for hGH were not significantly different from those reported for the particulate membrane preparation. The solubilization process did not appear to alter the binding protein(s) therefore, and permits a further study of the isolation, purification and properties of the binding protein(s) itself.", "contents": "Solubilization of a growth hormone-specific receptor from rabbit liver. Membrane preparations from rabbit liver, known to possess GH-specific binding sites, have been solubilized with Triton X-100 and the binding characteristics of [125I]-human GH (hGH) and [125I]-bovine GH (bGH) subsequently studied. Specific binding of the hGH and bGH by the solubilized preparation was demonstrated of bound and free hormone by either polyethylene glycol precipitation or by Sephadex G-100 chromatography. Binding of hGH was both rapid and reversible and was displaced only by other growth hormones (bovine and ovine) and not by lactogenic hormones (ovine and human prolactins, human placental lactogen). As shown by Scatchard analysis specific binding of [125I]-bGH exhibited a lower binding affinity and capacity than did [125I]-hGH. Overall, the characteristics of the binding reaction for hGH were not significantly different from those reported for the particulate membrane preparation. The solubilization process did not appear to alter the binding protein(s) therefore, and permits a further study of the isolation, purification and properties of the binding protein(s) itself."}
{"id": "PMID:196841", "title": "Phenytoin, electric, ionic, and metabolic responses in cortex and spinal cord.", "content": "Post-tetanic potentiation (PTP) of monosynaptic reflex was estimated in spinal cords in the drug-free state after the administration of a convulsant dose of penicillin and after the administration of phenytoin. There was no apparent correlation between the degree of depression of PTP and the efficacy of controlling seizure activity by phenytoin. Extracellular potassium levels were measured with ion-selective microelectrodes. The post-stimulation clearing of [K+]0 was not accelerated by phenytoin, and frequently it was slowed. Post-stimulus undershooting of [K+]0 was diminished. Oxidation of NADH in cortex and of cytochrome a, a3 in spinal cord were measured by optical methods. Stimulus-evoked transient oxidation responses evoked by electrical stimulation were depressed by phenytoin. It is concluded that systemic administration of phenytoin in therapeutic doses does not stimulate Na+-K+-activated membrane ATPase in cortex and spinal cord. Unlike other depressants, phenytoin did not cause a reduction of \"resting\" redox levels of respiratory enzymes. The local regulation of blood flow remained unaltered after phenytoin administration. Phenytoin caused a moderate but consistent depression of the stimulus-evoked responses of potassium activity, electric potential, and oxidative enzymes, consistent with diminished outflow of potassium from cells, owing either to lesser activation of cells or to a lesser exchange of ions.", "contents": "Phenytoin, electric, ionic, and metabolic responses in cortex and spinal cord. Post-tetanic potentiation (PTP) of monosynaptic reflex was estimated in spinal cords in the drug-free state after the administration of a convulsant dose of penicillin and after the administration of phenytoin. There was no apparent correlation between the degree of depression of PTP and the efficacy of controlling seizure activity by phenytoin. Extracellular potassium levels were measured with ion-selective microelectrodes. The post-stimulation clearing of [K+]0 was not accelerated by phenytoin, and frequently it was slowed. Post-stimulus undershooting of [K+]0 was diminished. Oxidation of NADH in cortex and of cytochrome a, a3 in spinal cord were measured by optical methods. Stimulus-evoked transient oxidation responses evoked by electrical stimulation were depressed by phenytoin. It is concluded that systemic administration of phenytoin in therapeutic doses does not stimulate Na+-K+-activated membrane ATPase in cortex and spinal cord. Unlike other depressants, phenytoin did not cause a reduction of \"resting\" redox levels of respiratory enzymes. The local regulation of blood flow remained unaltered after phenytoin administration. Phenytoin caused a moderate but consistent depression of the stimulus-evoked responses of potassium activity, electric potential, and oxidative enzymes, consistent with diminished outflow of potassium from cells, owing either to lesser activation of cells or to a lesser exchange of ions."}
{"id": "PMID:196842", "title": "Phenytoin: effects on calcium flux and cyclic nucleotides.", "content": "Previous studies have demonstrated that phenytoin alters calcium conductance in isolated presynaptic nerve endings (synaptosomes) from rat or rabbit brain. Drug concentrations of 0.08 mM (20 microgram/ml) or higher inhibit stimulated calcium influx into synaptosomes depolarized by high concentrations of potassium (69 mM) by 7-58%. Calcium transport into undepolarized synaptosomes is only inhibited by 0.4 mM or greater concentrations of phenytoin. Recent investigations show that in mouse brain slices, phenytoin inhibited elevations of cyclic GMP and cyclic AMP produced by ouabain or veratridine. In contrast, elevations of the two cyclic nucleotides produced by high concentrations of potassium were not inhibited by phenytoin, suggesting that the anticonvulsant suppresses depolarization-induced elevation of cyclic nucleotide levels in brain slices by inhibiting influx of sodium into cells. These data indicate that phenytoin inhibits both sodium and calcium influx into cells during cellular depolarization and alters regulation of brain cyclic nucleotide levels. Both of these actions may be important for the antiepileptic effect of phenytoin.", "contents": "Phenytoin: effects on calcium flux and cyclic nucleotides. Previous studies have demonstrated that phenytoin alters calcium conductance in isolated presynaptic nerve endings (synaptosomes) from rat or rabbit brain. Drug concentrations of 0.08 mM (20 microgram/ml) or higher inhibit stimulated calcium influx into synaptosomes depolarized by high concentrations of potassium (69 mM) by 7-58%. Calcium transport into undepolarized synaptosomes is only inhibited by 0.4 mM or greater concentrations of phenytoin. Recent investigations show that in mouse brain slices, phenytoin inhibited elevations of cyclic GMP and cyclic AMP produced by ouabain or veratridine. In contrast, elevations of the two cyclic nucleotides produced by high concentrations of potassium were not inhibited by phenytoin, suggesting that the anticonvulsant suppresses depolarization-induced elevation of cyclic nucleotide levels in brain slices by inhibiting influx of sodium into cells. These data indicate that phenytoin inhibits both sodium and calcium influx into cells during cellular depolarization and alters regulation of brain cyclic nucleotide levels. Both of these actions may be important for the antiepileptic effect of phenytoin."}
{"id": "PMID:196843", "title": "Effects of phenytoin on the cyclic nucleotide system in the motor nerve terminal.", "content": "The effects of phenytoin on the motor nerve terminal were evaluated on the in vivo cat soleus nerve muscle preparation. Phenytoin, 10 mg/kg, reduced the repetitive aftercharges in motor nerve endings due to tetanic conditioning. It also reduced the repetitive activity due to adenylate cyclase activation with NaF, or to exogeneous dibutyryl cyclic AMP. These effects of phenytoin could be reversed by administering theophylline, a phosphodiesterase inhibitor, or by increasing the extracellular concentration of calcium. The effects of phenytoin could also be reversed by 3-aminopyridine, but not by tetraethylammonium chloride. Verapamil, a calcium current antagonist, produced effects that were identical to phenytoin. It is concluded that phenytoin blocks a cyclic nucleotide-mediated calcium influx that is associated with transmitter release. This calcium flux also appears to control a slow potassium current that is responsible for post-tetanic hyperpolarization.", "contents": "Effects of phenytoin on the cyclic nucleotide system in the motor nerve terminal. The effects of phenytoin on the motor nerve terminal were evaluated on the in vivo cat soleus nerve muscle preparation. Phenytoin, 10 mg/kg, reduced the repetitive aftercharges in motor nerve endings due to tetanic conditioning. It also reduced the repetitive activity due to adenylate cyclase activation with NaF, or to exogeneous dibutyryl cyclic AMP. These effects of phenytoin could be reversed by administering theophylline, a phosphodiesterase inhibitor, or by increasing the extracellular concentration of calcium. The effects of phenytoin could also be reversed by 3-aminopyridine, but not by tetraethylammonium chloride. Verapamil, a calcium current antagonist, produced effects that were identical to phenytoin. It is concluded that phenytoin blocks a cyclic nucleotide-mediated calcium influx that is associated with transmitter release. This calcium flux also appears to control a slow potassium current that is responsible for post-tetanic hyperpolarization."}
{"id": "PMID:196846", "title": "Effect of salt loading in the rat on adenylate cyclase and phosphodiesterase activity in kidney cortex, medulla and papilla.", "content": "Adenylate cyclase (AC) and phosphodiesterase (PDE) activities were studied in the cortex, medulla and papilla of the rat kidney. Sodium loading in vivo for 14 days resulted in a decrease of AC activity in the cortex, a small increase in the medulla and a substantial increase of AC activity in the papilla. Sodium loading caused reciprocal effects on PDE activity: an increase in kidney cortex and a decrease in kidney papilla. Loading of glucose in vivo or chronic administration of antidiuretic hormone in vivo did not cause the changes in AC or PDE observed after sodium loading. The possible significance of these findings is discussed.", "contents": "Effect of salt loading in the rat on adenylate cyclase and phosphodiesterase activity in kidney cortex, medulla and papilla. Adenylate cyclase (AC) and phosphodiesterase (PDE) activities were studied in the cortex, medulla and papilla of the rat kidney. Sodium loading in vivo for 14 days resulted in a decrease of AC activity in the cortex, a small increase in the medulla and a substantial increase of AC activity in the papilla. Sodium loading caused reciprocal effects on PDE activity: an increase in kidney cortex and a decrease in kidney papilla. Loading of glucose in vivo or chronic administration of antidiuretic hormone in vivo did not cause the changes in AC or PDE observed after sodium loading. The possible significance of these findings is discussed."}
{"id": "PMID:196847", "title": "Unspecific arginine kinase of molecular weight 150 000. Amino acid composition, subunit structure and number of substrate binding sites.", "content": "The amino acid composition of unspecific arginine kinase of molecular weight 150 000 of Sabella pavonina muscle has been determined. If was found to be very similar to that of the phosphagen kinases previously studied. The subunit structure of the enzyme has been investigated by physical and chemical means. The data obtained from ultracentrifugation studies in 6 M guanidine hydrochloride and from molecular sieving and disc electrophoresis in 8 M urea, as well as the tryptic peptide mapping, suggest that Sabella muscle kinase is composed of four non-covalently linked polypeptide chains, with similar molecular weights. The number of binding sites for the nucleotide substrate ADP-Mg2+ has been estimated, using differential spectrophotometry and gel filtration on Sephadex columns. By both methods it was demonstrated that the enzyme contains two catalytic sites per protein molecule of molecular weight 150 000. Thus, arginine kinase from Sabella muscle, of molecular weight 150 000, consists of four similar polypeptide chains, but possesses only two substrate binding sites per tetrameric molecule.", "contents": "Unspecific arginine kinase of molecular weight 150 000. Amino acid composition, subunit structure and number of substrate binding sites. The amino acid composition of unspecific arginine kinase of molecular weight 150 000 of Sabella pavonina muscle has been determined. If was found to be very similar to that of the phosphagen kinases previously studied. The subunit structure of the enzyme has been investigated by physical and chemical means. The data obtained from ultracentrifugation studies in 6 M guanidine hydrochloride and from molecular sieving and disc electrophoresis in 8 M urea, as well as the tryptic peptide mapping, suggest that Sabella muscle kinase is composed of four non-covalently linked polypeptide chains, with similar molecular weights. The number of binding sites for the nucleotide substrate ADP-Mg2+ has been estimated, using differential spectrophotometry and gel filtration on Sephadex columns. By both methods it was demonstrated that the enzyme contains two catalytic sites per protein molecule of molecular weight 150 000. Thus, arginine kinase from Sabella muscle, of molecular weight 150 000, consists of four similar polypeptide chains, but possesses only two substrate binding sites per tetrameric molecule."}
{"id": "PMID:196849", "title": "2-O-(beta-D-glucuronyl)-7-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-L-glycero-D-manno-heptose: a constituent of the Bordetella pertussis endotoxin.", "content": "The presence of bound D-glucuronic acid in the endotoxin of Bordetella pertussis was demonstrated. The branched chain trisaccharide named in the title was isolated after hydrolysis of the endotoxin with 3 M HCl for 2 h at 100 degrees C. Its structure was established by chemical and enzymic degradation.", "contents": "2-O-(beta-D-glucuronyl)-7-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-L-glycero-D-manno-heptose: a constituent of the Bordetella pertussis endotoxin. The presence of bound D-glucuronic acid in the endotoxin of Bordetella pertussis was demonstrated. The branched chain trisaccharide named in the title was isolated after hydrolysis of the endotoxin with 3 M HCl for 2 h at 100 degrees C. Its structure was established by chemical and enzymic degradation."}
{"id": "PMID:196851", "title": "Characterization of a soluble simian-virus-40 transcription complex.", "content": "We have previously described the isolation, from nuclei of monkey cells infected with Simian virus 40 (SV40), of a nucleoprotein complex which is able to achieve viral transcription. This complex contains SV40 DNA and RNA polymerase II molecules which have initiated transcription during the viral development. We show here, by molecular hybridization experiments, that most of the templates active in SV40 transcription can be dissociated from host DNA. In conditions where supercoiled SV40 DNA form I sediments at 21 S, the transcription complex has a sedimentation coefficient of about 25 S. Inhibition of viral DNA synthesis by cytosine arabinonucleoside or chloroquine does not affect the activity of the transcription complex, which suggests that replicating molecules are not required for viral RNA synthesis and that SV40 DNA form I could serve as template for late SV40 transcription. A large fraction of the RNA synthesized in vitro remains associated with the SV40 DNA template in cesium sulfate density gradient. The RNA chains produced by the complex are heterogeneous in size, most of them being as large or larger than the viral genome.", "contents": "Characterization of a soluble simian-virus-40 transcription complex. We have previously described the isolation, from nuclei of monkey cells infected with Simian virus 40 (SV40), of a nucleoprotein complex which is able to achieve viral transcription. This complex contains SV40 DNA and RNA polymerase II molecules which have initiated transcription during the viral development. We show here, by molecular hybridization experiments, that most of the templates active in SV40 transcription can be dissociated from host DNA. In conditions where supercoiled SV40 DNA form I sediments at 21 S, the transcription complex has a sedimentation coefficient of about 25 S. Inhibition of viral DNA synthesis by cytosine arabinonucleoside or chloroquine does not affect the activity of the transcription complex, which suggests that replicating molecules are not required for viral RNA synthesis and that SV40 DNA form I could serve as template for late SV40 transcription. A large fraction of the RNA synthesized in vitro remains associated with the SV40 DNA template in cesium sulfate density gradient. The RNA chains produced by the complex are heterogeneous in size, most of them being as large or larger than the viral genome."}
{"id": "PMID:196852", "title": "Determination of the syn-anti equilibrium of some purine 3':5'-nucleotides by nuclear-magnetic-relaxation perturbation in the presence of a lanthanide-ion probe.", "content": "The aqueous solution conformation of four purine 3':5'-nucleotides varying in their substituents at C-6 and C-8 has been studied using gadolinium(III) to perturb the proton relaxation times. The ribose conformations are inferred. All the nucleotides are best described as being in a dynamic equilibrium between syn and anti conformations and the position of this equilibrium is not dramatically affected by changing the substituent at C-6. These nucleotides in their neutral base form slightly favour an anti conformation. In the presence of a bulky methylthio group at C-8 the equilibrium is shifted towards a dominance from the syn conformation due to steric repulsion factors.", "contents": "Determination of the syn-anti equilibrium of some purine 3':5'-nucleotides by nuclear-magnetic-relaxation perturbation in the presence of a lanthanide-ion probe. The aqueous solution conformation of four purine 3':5'-nucleotides varying in their substituents at C-6 and C-8 has been studied using gadolinium(III) to perturb the proton relaxation times. The ribose conformations are inferred. All the nucleotides are best described as being in a dynamic equilibrium between syn and anti conformations and the position of this equilibrium is not dramatically affected by changing the substituent at C-6. These nucleotides in their neutral base form slightly favour an anti conformation. In the presence of a bulky methylthio group at C-8 the equilibrium is shifted towards a dominance from the syn conformation due to steric repulsion factors."}
{"id": "PMID:196853", "title": "Incorporation of the 1-pro-R and the 1-pro-S hydrogen atoms of ethanol into steroids and phosphatidylcholines in vivo.", "content": "The transfer of deuterium from chiral 1-monodeuteroethanols to various metabolites formed in the liver was studied in order to investigate the coupling of metabolic reductions to the alcohol dehydrogenase and the aldehyde dehydrogenase reactions. The ethanols were administered to female bile fistula rats for 10 h. The hydrogen at C-2 in the glycerol moiety of newly formed phosphatidylcholine molecules in bile, liver and plasma was derived to 22-25% from the 1-pro-R position and to 5-6% from the 1-pro-S position in the ethanol. sn-Glycerol 3-phosphate isolated from liver had a lower deuterium content at C-2. The ratio between the contributions from the two positions in ethanol to C-2 of free sn-glycerol 3-phosphate was the same as in the phosphatidylcholines. This indicates that the higher degree of labelling of this position in phosphatidylcholines is not due to a specific coupling between alcohol dehydrogenase and the formation of a phosphatidylcholine precursor. Cholesterol and chenodeoxycholic acid in bile became increasingly labelled, and the ratio between the incorporations from the 1-pro-S and the 1-pro-R positions of ethanol was about 0.37 in cholesterol and 0.46 in chenodeoxycholic acid. Thus, these NADPH-dependent reactions utilized hydrogen from the 1-pro-S position to a larger extent than NADH-dependent reactions.", "contents": "Incorporation of the 1-pro-R and the 1-pro-S hydrogen atoms of ethanol into steroids and phosphatidylcholines in vivo. The transfer of deuterium from chiral 1-monodeuteroethanols to various metabolites formed in the liver was studied in order to investigate the coupling of metabolic reductions to the alcohol dehydrogenase and the aldehyde dehydrogenase reactions. The ethanols were administered to female bile fistula rats for 10 h. The hydrogen at C-2 in the glycerol moiety of newly formed phosphatidylcholine molecules in bile, liver and plasma was derived to 22-25% from the 1-pro-R position and to 5-6% from the 1-pro-S position in the ethanol. sn-Glycerol 3-phosphate isolated from liver had a lower deuterium content at C-2. The ratio between the contributions from the two positions in ethanol to C-2 of free sn-glycerol 3-phosphate was the same as in the phosphatidylcholines. This indicates that the higher degree of labelling of this position in phosphatidylcholines is not due to a specific coupling between alcohol dehydrogenase and the formation of a phosphatidylcholine precursor. Cholesterol and chenodeoxycholic acid in bile became increasingly labelled, and the ratio between the incorporations from the 1-pro-S and the 1-pro-R positions of ethanol was about 0.37 in cholesterol and 0.46 in chenodeoxycholic acid. Thus, these NADPH-dependent reactions utilized hydrogen from the 1-pro-S position to a larger extent than NADH-dependent reactions."}
{"id": "PMID:196856", "title": "Preparation of N6-[N-(6-aminohexyl) carbamoyl]-adenine nucleotides and their application to coenzymically active immobilized ADP and ATP, and affinity adsorbents.", "content": "Reaction of ADP with hexamethylene diisocyanate in hexamethylphosphoramide followed by treatment in an acidic medium afforded three new adenine nucleotide analogues, N6-[N-(6-aminohexyl)carbamoyl]-ADP, N6-[N-(6-aminohexyl)carbamoyl]-ATP, and N6-[N-(6-aminohexyl)carbamoyl]-AMP in yields of 13%, 12% and 17%, respectively. The occurrence of the ATP analogue may be interpreted in terms of the equilibrium, 2ADP = ATP + AMP. Coenzymic activities of the ADP analogue against acetate kinase and pyruvate kinase were 82% and 20%, respectively, relative to ADP and those of the ATP analogue against hexokinase and glycerokinase were 63% and 87%, respectively, relative to ATP. These analogues were bound to CNBr-activated soluble dextran through their terminal amino group to give an immobilized ADP and an immobilized ATP, each of which was recycled in a system comprising acetate kinase and hexokinase, and when placed in a membrane reactor together with the enzymes, functioned as an immobilized coenzyme continuously yielding glucose 6-phosphate. A series of chemically defined affinity adsorbents were obtained by coupling these analogues to CNBr-activated Sepharose, and were used to separate the enzymes in a mixture of hexokinase, pyruvate kinase, phosphoglycerate kinase, lactate dehydrogenase, and alcohol dehydrogenase.", "contents": "Preparation of N6-[N-(6-aminohexyl) carbamoyl]-adenine nucleotides and their application to coenzymically active immobilized ADP and ATP, and affinity adsorbents. Reaction of ADP with hexamethylene diisocyanate in hexamethylphosphoramide followed by treatment in an acidic medium afforded three new adenine nucleotide analogues, N6-[N-(6-aminohexyl)carbamoyl]-ADP, N6-[N-(6-aminohexyl)carbamoyl]-ATP, and N6-[N-(6-aminohexyl)carbamoyl]-AMP in yields of 13%, 12% and 17%, respectively. The occurrence of the ATP analogue may be interpreted in terms of the equilibrium, 2ADP = ATP + AMP. Coenzymic activities of the ADP analogue against acetate kinase and pyruvate kinase were 82% and 20%, respectively, relative to ADP and those of the ATP analogue against hexokinase and glycerokinase were 63% and 87%, respectively, relative to ATP. These analogues were bound to CNBr-activated soluble dextran through their terminal amino group to give an immobilized ADP and an immobilized ATP, each of which was recycled in a system comprising acetate kinase and hexokinase, and when placed in a membrane reactor together with the enzymes, functioned as an immobilized coenzyme continuously yielding glucose 6-phosphate. A series of chemically defined affinity adsorbents were obtained by coupling these analogues to CNBr-activated Sepharose, and were used to separate the enzymes in a mixture of hexokinase, pyruvate kinase, phosphoglycerate kinase, lactate dehydrogenase, and alcohol dehydrogenase."}
{"id": "PMID:196857", "title": "Identification of 2-methyl-3-hydroxydecanoic and 2-methyl-3-hydroxytetradecanoic acids in the 'lipid X' fraction of the Bordetella pertussis endotoxin.", "content": "The 'lipid X' fraction, released from the Bordetella pertussis endotoxin upon treatment with trifluoroacetic acid of pH 3 at 50 degrees C, was shown to contain, in addition to 3-hydroxydecanoic, 3-hydroxydodecanoic, 3-hydroxytetradecanoic, and tetradec-2-enoic acids, 2-methyl-3-hydroxydecanoic-, and 2-methyl-3-hydroxytetradecanoic acids. The structure of these was established by gas-liquid chromatography/mass spectrometry.", "contents": "Identification of 2-methyl-3-hydroxydecanoic and 2-methyl-3-hydroxytetradecanoic acids in the 'lipid X' fraction of the Bordetella pertussis endotoxin. The 'lipid X' fraction, released from the Bordetella pertussis endotoxin upon treatment with trifluoroacetic acid of pH 3 at 50 degrees C, was shown to contain, in addition to 3-hydroxydecanoic, 3-hydroxydodecanoic, 3-hydroxytetradecanoic, and tetradec-2-enoic acids, 2-methyl-3-hydroxydecanoic-, and 2-methyl-3-hydroxytetradecanoic acids. The structure of these was established by gas-liquid chromatography/mass spectrometry."}
{"id": "PMID:196859", "title": "Impaired responsiveness to the effect of glucagon on plasma adenosine 3':5'-cyclic monophosphate in normal man.", "content": "Small doses (10-150 microgram; 3-45 nmol) of glucagon caused a dose-dependent increase in plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) concentration when injected into man. Infusion of glucagon (75 ng min-1 kg-1) for 2 h into normal subjects resulted in an initial increase in plasma cyclic AMP concentration, then a decline despite continuation of the hormone infusion and maintenance of high concentrations of circulating immunoreactive glucagon. When an injection of glucagon was given at the termination of such an infusion, the subsequent increase in plasma cyclic AMP concentration was markedly reduced when compared to that observed after a control injection which had not been preceded by a glucagon infusion. When the glucagon was injected at the end of an infusion of 1000 MRC units of bovine parathyroid hormone (BPTH) over 2 h, the plasma cyclic AMP response was normal. Conversely, after infusion of glucagon the response to injected BPTH was normal. This impairment of response was therefore specific to the hormone that had been administered and was not due to altered metabolism of circulating cyclic AMP. This phenomenon may be important in the regulation of the hormonal response by the target tissue.", "contents": "Impaired responsiveness to the effect of glucagon on plasma adenosine 3':5'-cyclic monophosphate in normal man. Small doses (10-150 microgram; 3-45 nmol) of glucagon caused a dose-dependent increase in plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) concentration when injected into man. Infusion of glucagon (75 ng min-1 kg-1) for 2 h into normal subjects resulted in an initial increase in plasma cyclic AMP concentration, then a decline despite continuation of the hormone infusion and maintenance of high concentrations of circulating immunoreactive glucagon. When an injection of glucagon was given at the termination of such an infusion, the subsequent increase in plasma cyclic AMP concentration was markedly reduced when compared to that observed after a control injection which had not been preceded by a glucagon infusion. When the glucagon was injected at the end of an infusion of 1000 MRC units of bovine parathyroid hormone (BPTH) over 2 h, the plasma cyclic AMP response was normal. Conversely, after infusion of glucagon the response to injected BPTH was normal. This impairment of response was therefore specific to the hormone that had been administered and was not due to altered metabolism of circulating cyclic AMP. This phenomenon may be important in the regulation of the hormonal response by the target tissue."}
{"id": "PMID:196860", "title": "Lipoprotein-X: a substrate for lecithin: cholesterol acyltransferase.", "content": "The action of lecithin:cholesterol acyltransferase (LCAT) was studied on an abnormal lipoprotein (LP-X) rich in phosphatidylcholine and cholesterol from the plasma of patients with obstructive liver disease. 60 mg LP-X isolated free of other lipoproteins and subsequently labelled with 3H-cholesterol were incubated with 1 mg highly purified enzyme in the presence of albumin. After 45 h at 37 degrees C, the incubation mixture was subjected to zonal ultracentrifugation. 3H-cholesterol and 3H-cholesteryl esters were quantified in each fraction of the zonal gradient. More than 95% of the lipoproteins in this mixture banded in the density range of LP-X with no change in size distribution, but did contain 593 nmoles of newly formed cholesteryl esters. Agarose electrophoresis revealed an alpha-migrating band in addition to the original beta-band. Also on agar, the typically cathode migrating LP-X was changed to anode moving material. These studies indicate that LP-X can serve as a substrate for LCAT.", "contents": "Lipoprotein-X: a substrate for lecithin: cholesterol acyltransferase. The action of lecithin:cholesterol acyltransferase (LCAT) was studied on an abnormal lipoprotein (LP-X) rich in phosphatidylcholine and cholesterol from the plasma of patients with obstructive liver disease. 60 mg LP-X isolated free of other lipoproteins and subsequently labelled with 3H-cholesterol were incubated with 1 mg highly purified enzyme in the presence of albumin. After 45 h at 37 degrees C, the incubation mixture was subjected to zonal ultracentrifugation. 3H-cholesterol and 3H-cholesteryl esters were quantified in each fraction of the zonal gradient. More than 95% of the lipoproteins in this mixture banded in the density range of LP-X with no change in size distribution, but did contain 593 nmoles of newly formed cholesteryl esters. Agarose electrophoresis revealed an alpha-migrating band in addition to the original beta-band. Also on agar, the typically cathode migrating LP-X was changed to anode moving material. These studies indicate that LP-X can serve as a substrate for LCAT."}
{"id": "PMID:196864", "title": "The actions of three diaminopyridines on the chick biventer cervicis muscle.", "content": "The effects of 2,3-, 2,6- and 3,4-diaminopyridine were investigated on the isolated chick biventer cervicis muscle preparation. All three compounds reversed tubocurarine blockade and augmented twitch height in indirectly stimulated preparations. Less twitch augmentation was observed in directly stimulated preparations. 3,4-Diaminopyridine was the most effective of the compounds in facilitating neuromuscular transmission, but exhibited less convulsant activity than 4-aminopyridine. 3,4- and 2,3-diaminopyridine in high concentrations caused contractures that were inhibited by erabutoxin b or by beta-bungarotoxin. It is suggested that the diaminopyridines increase both evoked and spontaneous acetylcholine release.", "contents": "The actions of three diaminopyridines on the chick biventer cervicis muscle. The effects of 2,3-, 2,6- and 3,4-diaminopyridine were investigated on the isolated chick biventer cervicis muscle preparation. All three compounds reversed tubocurarine blockade and augmented twitch height in indirectly stimulated preparations. Less twitch augmentation was observed in directly stimulated preparations. 3,4-Diaminopyridine was the most effective of the compounds in facilitating neuromuscular transmission, but exhibited less convulsant activity than 4-aminopyridine. 3,4- and 2,3-diaminopyridine in high concentrations caused contractures that were inhibited by erabutoxin b or by beta-bungarotoxin. It is suggested that the diaminopyridines increase both evoked and spontaneous acetylcholine release."}
{"id": "PMID:196865", "title": "Rat gastric mucosal cAMP and cGMP after adrenergic stimulation and blockade.", "content": "The effect of adrenergic stimulation and blockade on the concentration of cAMP and cGMP was studied in the rat gastric mucosa. Adrenaline (0.5-2.0 mg/kg) elevated the gastric mucosal cAMP and cGMP levels up to 100% in a dose-dependent manner. Blockade of the beta-adrenoceptors with 4 mg/kg propranolol suppressed the adrenaline effect on the cAMP level and increased the effect on the cGMP concentration up to 500%. The opposite effect was found under alpha-adrenoceptor blockade. Phenoxybenzamine, 4 mg/kg, prevented the adrenaline effect on the cGMP level and increased the effect on the cAMP concentration up to 300%. Predominant stimulation of the beta-adrenoceptors by isoproterenol or of the alpha-adrenoceptors by phenylephrine caused smaller changes in the cyclic nucleotide concentration than did adrenaline. Their effect was more pronounced when the non-stimulated receptor was blocked. The data indicate that the rat gastric mucosa contains alpha- and beta-adrenoceptors. The effect of adrenaline on the gastric mucosal cAMP level is mediated by beta-adrenoceptors and that on the cGMP level by alpha-adrenoceptors.", "contents": "Rat gastric mucosal cAMP and cGMP after adrenergic stimulation and blockade. The effect of adrenergic stimulation and blockade on the concentration of cAMP and cGMP was studied in the rat gastric mucosa. Adrenaline (0.5-2.0 mg/kg) elevated the gastric mucosal cAMP and cGMP levels up to 100% in a dose-dependent manner. Blockade of the beta-adrenoceptors with 4 mg/kg propranolol suppressed the adrenaline effect on the cAMP level and increased the effect on the cGMP concentration up to 500%. The opposite effect was found under alpha-adrenoceptor blockade. Phenoxybenzamine, 4 mg/kg, prevented the adrenaline effect on the cGMP level and increased the effect on the cAMP concentration up to 300%. Predominant stimulation of the beta-adrenoceptors by isoproterenol or of the alpha-adrenoceptors by phenylephrine caused smaller changes in the cyclic nucleotide concentration than did adrenaline. Their effect was more pronounced when the non-stimulated receptor was blocked. The data indicate that the rat gastric mucosa contains alpha- and beta-adrenoceptors. The effect of adrenaline on the gastric mucosal cAMP level is mediated by beta-adrenoceptors and that on the cGMP level by alpha-adrenoceptors."}
{"id": "PMID:196875", "title": "The effects of brainstem priming stimulation on interhemispheric hippocampal responses in the awake rat.", "content": "Evoked hippocampal responses to stimulation of the contralateral hippocampus were recorded in the awake rat. The effects of priming stimulation applied to the nucleus locus coeruleus and the raphe nuclei on averaged evoked hippocampal responses to the interhemispheric stimulation were measured. It was found that priming stimulation of these monoamine-containing nuclei caused the formation of a late component in the interhemispheric potential without affecting the magnitude of the initial response component. Drugs which selectively interfere with noradrenergic or serotonergic transmission, antagonized the locus coeruleus or raphe primed late response component, respectively. Parenteral administration of d-amphetamine or l-amphetamine caused the appearance of a late response component which was similar to that seen after brainstem priming stimulation. It is suggested that the monoamines modify responses to afferent stimulation of particular pathways in the brain.", "contents": "The effects of brainstem priming stimulation on interhemispheric hippocampal responses in the awake rat. Evoked hippocampal responses to stimulation of the contralateral hippocampus were recorded in the awake rat. The effects of priming stimulation applied to the nucleus locus coeruleus and the raphe nuclei on averaged evoked hippocampal responses to the interhemispheric stimulation were measured. It was found that priming stimulation of these monoamine-containing nuclei caused the formation of a late component in the interhemispheric potential without affecting the magnitude of the initial response component. Drugs which selectively interfere with noradrenergic or serotonergic transmission, antagonized the locus coeruleus or raphe primed late response component, respectively. Parenteral administration of d-amphetamine or l-amphetamine caused the appearance of a late response component which was similar to that seen after brainstem priming stimulation. It is suggested that the monoamines modify responses to afferent stimulation of particular pathways in the brain."}
{"id": "PMID:196876", "title": "The mode of synaptic linkage in the cerebro-ponto-cerebellar pathway investigated with intracellular recording from pontine nuclei cells of the cat.", "content": "1. Intracellular potentials of pontine nuclei (PN) cells were recorded in cats anesthetized with pentobarbitone sodium. 2. Stimulation of the cerebellar nuclear regions or the brachium pontis induced an antidromic action potential composed of IS-SD spikes, after-depolarization and after-hyperpolarization. 3. Cerebellar stimulation produced EPSPs only in a few PN cells. 4. Activation of the corticopontine or pyramidal tract produced in all PN cells an EPSP built up from the unitary components with variable amplitudes and time courses. Paired or repetitive activation revealed a property of the frequency potentiation of the EPSP. 5. Unitary EPSPs also occurred spontaneously. A great majority of these spontaneous EPSPs were cerebral in origin, and had amplitudes and time courses comparable with those evoked by stimulation of the corticopontine or pyramidal tract. 6. The half-width versus time of peak relationship of these unitary EPSPs suggested a dendritic location of the synapses with variable distances from the soma. It is assumed that large, proximal synapses serve for efficient relay of signals while small, distal synapses for their integration.", "contents": "The mode of synaptic linkage in the cerebro-ponto-cerebellar pathway investigated with intracellular recording from pontine nuclei cells of the cat. 1. Intracellular potentials of pontine nuclei (PN) cells were recorded in cats anesthetized with pentobarbitone sodium. 2. Stimulation of the cerebellar nuclear regions or the brachium pontis induced an antidromic action potential composed of IS-SD spikes, after-depolarization and after-hyperpolarization. 3. Cerebellar stimulation produced EPSPs only in a few PN cells. 4. Activation of the corticopontine or pyramidal tract produced in all PN cells an EPSP built up from the unitary components with variable amplitudes and time courses. Paired or repetitive activation revealed a property of the frequency potentiation of the EPSP. 5. Unitary EPSPs also occurred spontaneously. A great majority of these spontaneous EPSPs were cerebral in origin, and had amplitudes and time courses comparable with those evoked by stimulation of the corticopontine or pyramidal tract. 6. The half-width versus time of peak relationship of these unitary EPSPs suggested a dendritic location of the synapses with variable distances from the soma. It is assumed that large, proximal synapses serve for efficient relay of signals while small, distal synapses for their integration."}
{"id": "PMID:196882", "title": "Information processing along the course of a visual interneuron.", "content": "Locust ocellar retinal cells are innervated by giant second order cells, 2 mm long, which show discrete zones of integration along their course, including a major zone in the axonal length of the neuron. The complex synaptic arrangements which exist between higher-order afferent and efferent cells and these second order cells along their course suggests that transmission takes place by the electrotonic spread of slow potentials. The size and accessibility of these visual interneurons offers a unique preparation for examining mechanisms of graded synaptic transmission.", "contents": "Information processing along the course of a visual interneuron. Locust ocellar retinal cells are innervated by giant second order cells, 2 mm long, which show discrete zones of integration along their course, including a major zone in the axonal length of the neuron. The complex synaptic arrangements which exist between higher-order afferent and efferent cells and these second order cells along their course suggests that transmission takes place by the electrotonic spread of slow potentials. The size and accessibility of these visual interneurons offers a unique preparation for examining mechanisms of graded synaptic transmission."}
{"id": "PMID:196883", "title": "Some properties of the goat placental lactogen.", "content": "Goat placental lactogen was partially purified from a medium collected after placental tissue incubation. The data obtained by disc electrophoresis and isoelectric focusing experiments, as well as by means of radioreceptor assay methods, provide evidence of the similarity between the goat and ovine placental lactogen.", "contents": "Some properties of the goat placental lactogen. Goat placental lactogen was partially purified from a medium collected after placental tissue incubation. The data obtained by disc electrophoresis and isoelectric focusing experiments, as well as by means of radioreceptor assay methods, provide evidence of the similarity between the goat and ovine placental lactogen."}
{"id": "PMID:196885", "title": "Isethionate may not be an inert substitute for extracellular chloride in the central nervous system.", "content": "Replacement of extracellular chloride with isethionate or methylsulphate causes an increased efflux of 1-[14C]-GABA from the in vivo superfused rat cuneate nucleus. This raises the question of the suitability of these anions as inert substitutes for chloride in studies on the ionic dependency of membrane phenomena in the central nervous system.", "contents": "Isethionate may not be an inert substitute for extracellular chloride in the central nervous system. Replacement of extracellular chloride with isethionate or methylsulphate causes an increased efflux of 1-[14C]-GABA from the in vivo superfused rat cuneate nucleus. This raises the question of the suitability of these anions as inert substitutes for chloride in studies on the ionic dependency of membrane phenomena in the central nervous system."}
{"id": "PMID:196887", "title": "Binding of ferritin-lectin conjugates to C-type virus in intact cells.", "content": "Ferritin-Ricin II and Ferritin-Concanavalin A bound to budding as well as mature C-type viral particles. No differencies in binding between the viral coat and adjacent plasma membrane were detected with either lectin conjugate. Aggregation of viral particles by lectin conjugates was observed, and linking of virus to the plasma membrane resulted in phagocytosis of viral particles.", "contents": "Binding of ferritin-lectin conjugates to C-type virus in intact cells. Ferritin-Ricin II and Ferritin-Concanavalin A bound to budding as well as mature C-type viral particles. No differencies in binding between the viral coat and adjacent plasma membrane were detected with either lectin conjugate. Aggregation of viral particles by lectin conjugates was observed, and linking of virus to the plasma membrane resulted in phagocytosis of viral particles."}
{"id": "PMID:196889", "title": "Effects of ACTH and diabetes on phospholipid metabolism in adrenal mitochondria.", "content": "Incorporation of 32P into adrenal mitochondrial phospholipids (PL) incrased in ACTH-treated rats, but it decreased in diabetics, inspite of the fact that these animals showed adrenal overacity. Since diabetics did not show increased 11 beta-hydroxylation. as opposed to ACTH-treated rats, it is suggested that the stimulation of this enzyme activity by exogenous ACTH is related to an increased turnover of PL at the mitochondrial membrane. The process is impaired in diabetics and prevents the stimulation of 11 beta-hydroxylation.", "contents": "Effects of ACTH and diabetes on phospholipid metabolism in adrenal mitochondria. Incorporation of 32P into adrenal mitochondrial phospholipids (PL) incrased in ACTH-treated rats, but it decreased in diabetics, inspite of the fact that these animals showed adrenal overacity. Since diabetics did not show increased 11 beta-hydroxylation. as opposed to ACTH-treated rats, it is suggested that the stimulation of this enzyme activity by exogenous ACTH is related to an increased turnover of PL at the mitochondrial membrane. The process is impaired in diabetics and prevents the stimulation of 11 beta-hydroxylation."}
{"id": "PMID:196890", "title": "Immunological studies on the key enzyme of arginine biosynthesis in Pseudomonas aeruginosa.", "content": "A method to manufacture specific antisera with a minute amount of prue enzyme is presented. The influence of antibodies on activity and inhibition of an allosterically regulated enzyme was studied.", "contents": "Immunological studies on the key enzyme of arginine biosynthesis in Pseudomonas aeruginosa. A method to manufacture specific antisera with a minute amount of prue enzyme is presented. The influence of antibodies on activity and inhibition of an allosterically regulated enzyme was studied."}
{"id": "PMID:196891", "title": "The effect of pyrophosphate and diphosphonates on calcium transport in red cells.", "content": "The effect of 0.5 mM pyrophosphate (PPi), disodium ethane-4-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethane diphosphonate (Cl2MDP) on the ATP-dependent Ca2+ extrusion from the human red cell ghosts was studied. PPi and Cl2MDP had no effect, when introduced into the cells or added outside to the medium. EHDP slightly increased the calcium concentration in the released cells and slightly decreased the rate constant of the calcium transport, having opposite effects when it was inside or outside the cells. PPi and the 2 diphosphonates were not found to move easily across the red cell membrane.", "contents": "The effect of pyrophosphate and diphosphonates on calcium transport in red cells. The effect of 0.5 mM pyrophosphate (PPi), disodium ethane-4-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethane diphosphonate (Cl2MDP) on the ATP-dependent Ca2+ extrusion from the human red cell ghosts was studied. PPi and Cl2MDP had no effect, when introduced into the cells or added outside to the medium. EHDP slightly increased the calcium concentration in the released cells and slightly decreased the rate constant of the calcium transport, having opposite effects when it was inside or outside the cells. PPi and the 2 diphosphonates were not found to move easily across the red cell membrane."}
{"id": "PMID:196892", "title": "Spin label studies of ATP phosphoribosyltransferase of E. coli.", "content": "Covalently bound bromoacetamide nitroxides have been used to detect the conformational changes and enzyme association induced by its feedback inhibitor, histidine.", "contents": "Spin label studies of ATP phosphoribosyltransferase of E. coli. Covalently bound bromoacetamide nitroxides have been used to detect the conformational changes and enzyme association induced by its feedback inhibitor, histidine."}
{"id": "PMID:196893", "title": "Effects of tricaine methane sulphonate (M.S. 222) on the blood glucose levels in adult salamanders (Diemictylus viridescens).", "content": "Exposure to M. S. 222 results in hyperglycemia in adult newts (Diemictylus viridescens). A combination of higher anesthetic concentrations with reduced exposure periods reduces the magnitude of this form of stress response.", "contents": "Effects of tricaine methane sulphonate (M.S. 222) on the blood glucose levels in adult salamanders (Diemictylus viridescens). Exposure to M. S. 222 results in hyperglycemia in adult newts (Diemictylus viridescens). A combination of higher anesthetic concentrations with reduced exposure periods reduces the magnitude of this form of stress response."}
{"id": "PMID:196894", "title": "Enhancement of virus growth produced by thiols and disulphides.", "content": "Several thiols and disulphides have been found able both to shorten the latency phase and to increase the growth of several virus strains in cell cultures.", "contents": "Enhancement of virus growth produced by thiols and disulphides. Several thiols and disulphides have been found able both to shorten the latency phase and to increase the growth of several virus strains in cell cultures."}
{"id": "PMID:196895", "title": "High density lipoproteins in ischaemic heart disease.", "content": "High density lipoprotein cholesterol concentrations were significantly lower in ischaemic heart disease patients than in healthy subjects when age and sex-matched. This difference was, however, not observed in the older age group (greater than 60 years).", "contents": "High density lipoproteins in ischaemic heart disease. High density lipoprotein cholesterol concentrations were significantly lower in ischaemic heart disease patients than in healthy subjects when age and sex-matched. This difference was, however, not observed in the older age group (greater than 60 years)."}
{"id": "PMID:196896", "title": "Effect of vinblastine on pancreatic enzymes secretion induced by cyclic nucleotide derivatives.", "content": "Vinblastine did not affect the basal secretion of enzymes from the rat pancreas, but it potentiates the secretory response to dibutyryl cyclic AMP. This potentiation is confirmed by the observation of numerous pictures of exocytosis at the apical part of the acinar cell. Dibutyryl cyclic GMP by itself, or associated with vinblastine, failed to modify the spontaneous release of enzymes or the secretion induced by dibutyryl cyclic AMP.", "contents": "Effect of vinblastine on pancreatic enzymes secretion induced by cyclic nucleotide derivatives. Vinblastine did not affect the basal secretion of enzymes from the rat pancreas, but it potentiates the secretory response to dibutyryl cyclic AMP. This potentiation is confirmed by the observation of numerous pictures of exocytosis at the apical part of the acinar cell. Dibutyryl cyclic GMP by itself, or associated with vinblastine, failed to modify the spontaneous release of enzymes or the secretion induced by dibutyryl cyclic AMP."}
{"id": "PMID:196897", "title": "Adrenergic supersensitivity of the pupil in idiopathic headache.", "content": "In idiopathic headache (IH) sufferers, phenylephrine and fenfluramine induce a pupillary dilatation respectively greater and lesser than in controls. The difference may be due to a supersensitivity of the iris alpha adrenoceptors caused by a deficiency of noradrenaline in the iris adrenergic nerve terminal of the IH sufferer. These findings seem to support the hypothesis of a brain receptorial, monoamine supersensitivity in IH.", "contents": "Adrenergic supersensitivity of the pupil in idiopathic headache. In idiopathic headache (IH) sufferers, phenylephrine and fenfluramine induce a pupillary dilatation respectively greater and lesser than in controls. The difference may be due to a supersensitivity of the iris alpha adrenoceptors caused by a deficiency of noradrenaline in the iris adrenergic nerve terminal of the IH sufferer. These findings seem to support the hypothesis of a brain receptorial, monoamine supersensitivity in IH."}
{"id": "PMID:196898", "title": "Opposite effect of PGE2 on cAMP levels in human adrenal medulla and pheochromocytoma.", "content": "PGE2 (10(-7) M) caused increased cAMP accumlation in 5 pheochromocytomas, while in 3 human adrenal medullae PGE2 caused a significant decrease of cAMP level on incubating slices in vitro. This finding is discussed in relation to the opposite effect of PGE2 on catecholamine release from human medulla and pheochromocytoma slices in vitro.", "contents": "Opposite effect of PGE2 on cAMP levels in human adrenal medulla and pheochromocytoma. PGE2 (10(-7) M) caused increased cAMP accumlation in 5 pheochromocytomas, while in 3 human adrenal medullae PGE2 caused a significant decrease of cAMP level on incubating slices in vitro. This finding is discussed in relation to the opposite effect of PGE2 on catecholamine release from human medulla and pheochromocytoma slices in vitro."}
{"id": "PMID:196899", "title": "Effects of N2, O2'-dibutyril cyclic GMP on the nucleoside phosphotransferase activity of the retina of the chick embryos.", "content": "In the retina of the chick embryo, 2 different forms of nucleoside phosphotransferase take part in the phosphorylation of thymidine. One is an unstable form with higher molecular weight. The other with lower m. wt is a stable form. This paper shows that N2,O2'-dibutyril cyclic GMP causes a marked decrement of the activity of the unstable nucleoside phosphotransferase.", "contents": "Effects of N2, O2'-dibutyril cyclic GMP on the nucleoside phosphotransferase activity of the retina of the chick embryos. In the retina of the chick embryo, 2 different forms of nucleoside phosphotransferase take part in the phosphorylation of thymidine. One is an unstable form with higher molecular weight. The other with lower m. wt is a stable form. This paper shows that N2,O2'-dibutyril cyclic GMP causes a marked decrement of the activity of the unstable nucleoside phosphotransferase."}
{"id": "PMID:196901", "title": "Alterations in the levels of cAMP and cGMP after decentralization of the rat superior cervical ganglion.", "content": "After cutting the preganglionic nerve trunk of the rat's superior cervical ganglion, the levels of cAMP and cGMP were measured in a postoperative period of between 3 and 21 dad by a partial recovery after 7 to 21 days.", "contents": "Alterations in the levels of cAMP and cGMP after decentralization of the rat superior cervical ganglion. After cutting the preganglionic nerve trunk of the rat's superior cervical ganglion, the levels of cAMP and cGMP were measured in a postoperative period of between 3 and 21 dad by a partial recovery after 7 to 21 days."}
{"id": "PMID:196903", "title": "Lysosomal enzyme release associated with the invasion of rat liver by Novikoff hepatoma.", "content": "The lysosomes of both Novikoff heptoma and liver from Novikoff heptoma-bearing rats were found to be relatively intact structurally, lower in acid phosphatase activity, greatly depleted in number but with nearly normal membrane integrity when compared with normal liver.", "contents": "Lysosomal enzyme release associated with the invasion of rat liver by Novikoff hepatoma. The lysosomes of both Novikoff heptoma and liver from Novikoff heptoma-bearing rats were found to be relatively intact structurally, lower in acid phosphatase activity, greatly depleted in number but with nearly normal membrane integrity when compared with normal liver."}
{"id": "PMID:196905", "title": "Studies on the effects of hormones on cholesterol synthesis in mammalian cells in culture.", "content": "The studies described here suggest the potential physiological role of polypeptide and corticosteroid hormones in the regulation of cholesterol synthesis. Evidence was shown for substantial differences between various cell types in their responses to these agents and for certain degree of independence of the effects on biosynthesis of cholesterol from those on protein and DNA synthesis. Cholesterol synthesis and HMGCoA reductase are stimulated in a number of diploid cell lines following an incubation with insulin or with glucocorticoids for 4 hr or longer. Stimulation of sterol synthesis by insulin and by dexamethasone requires protein synthesis, but the two hormones do not compete for the same site. Addition of glucagon or of dibutyryl cyclic AMP, or elevation of intracellular cyclic AMP by PGE1 does not inhibit cholesterol synthesis in skin fibroblasts. A possibility of a relationship between the mechanisms of the hormonal effects and of feedback control of cholesterol synthesis is suggested.", "contents": "Studies on the effects of hormones on cholesterol synthesis in mammalian cells in culture. The studies described here suggest the potential physiological role of polypeptide and corticosteroid hormones in the regulation of cholesterol synthesis. Evidence was shown for substantial differences between various cell types in their responses to these agents and for certain degree of independence of the effects on biosynthesis of cholesterol from those on protein and DNA synthesis. Cholesterol synthesis and HMGCoA reductase are stimulated in a number of diploid cell lines following an incubation with insulin or with glucocorticoids for 4 hr or longer. Stimulation of sterol synthesis by insulin and by dexamethasone requires protein synthesis, but the two hormones do not compete for the same site. Addition of glucagon or of dibutyryl cyclic AMP, or elevation of intracellular cyclic AMP by PGE1 does not inhibit cholesterol synthesis in skin fibroblasts. A possibility of a relationship between the mechanisms of the hormonal effects and of feedback control of cholesterol synthesis is suggested."}
{"id": "PMID:196908", "title": "The activation of lipoprotein lipase by lipase co-protein (apo C-2).", "content": "Kinetic analysis of activation of lipoprotein lipase by apo C-2 indicates that the lipase co-protein increase the rate of lipolysis by adsorption to enzyme at the lipid interface, with formation of a 1:1 molar complex, whose dissociation constant in the presence of triglyceride substrate is about 3 X 10(-13) moles cm-3. Activation by apo C-2, like that by the entire lipoprotein apoprotein moiety (Fielding and Fielding, 1976) is reversible by inorganic salts and the dependence of activation on medium ion-pair activity supports the concept that such inhibition is mediated through a single specific anion-binding site of the lipase co-protein.", "contents": "The activation of lipoprotein lipase by lipase co-protein (apo C-2). Kinetic analysis of activation of lipoprotein lipase by apo C-2 indicates that the lipase co-protein increase the rate of lipolysis by adsorption to enzyme at the lipid interface, with formation of a 1:1 molar complex, whose dissociation constant in the presence of triglyceride substrate is about 3 X 10(-13) moles cm-3. Activation by apo C-2, like that by the entire lipoprotein apoprotein moiety (Fielding and Fielding, 1976) is reversible by inorganic salts and the dependence of activation on medium ion-pair activity supports the concept that such inhibition is mediated through a single specific anion-binding site of the lipase co-protein."}
{"id": "PMID:196910", "title": "[Studies of substances with antiviral activity. VI. Activity on Herpes simplex virus of bis-homoanalogs of nucleosides and of hydrazone derivatives of various aromatic substrates].", "content": "Derivatives of different chemical structures, namely hydrazones of aromatic compounds and bis-homoanalogues of pyrimidine and purine nucleosides, have been investigated for inhibiting activity on Herpes simplex virus infection of human HEp-2 cell cultures. Some thiosemicarbazones, nucleoside analogues and guanylhydrazones proved active [compounds (I), (II b), (II c), (III), (IV a), (IV b), (V a), (V b); Fig. 1]. An increase in the number of guanylhydrazone chains linked to a fluorene structure [from 1 to 3: compounds (II a), (II b) and (II c)] increased the \"activity index\" (i.e., toxic versus active concentrations: Table II). Further in vitro investigations have been carried out on bis-guanylhydrazone of 1-phenyl-2-chloro-3,7-diformylindole (I) and it was found that its activity is of the order of 1 microgram per ml (Fig. 3). The compound completely blocks low multiplicity infections while it only blocks cytopathogenicity, not viral replication, in high multiplicity infections.", "contents": "[Studies of substances with antiviral activity. VI. Activity on Herpes simplex virus of bis-homoanalogs of nucleosides and of hydrazone derivatives of various aromatic substrates]. Derivatives of different chemical structures, namely hydrazones of aromatic compounds and bis-homoanalogues of pyrimidine and purine nucleosides, have been investigated for inhibiting activity on Herpes simplex virus infection of human HEp-2 cell cultures. Some thiosemicarbazones, nucleoside analogues and guanylhydrazones proved active [compounds (I), (II b), (II c), (III), (IV a), (IV b), (V a), (V b); Fig. 1]. An increase in the number of guanylhydrazone chains linked to a fluorene structure [from 1 to 3: compounds (II a), (II b) and (II c)] increased the \"activity index\" (i.e., toxic versus active concentrations: Table II). Further in vitro investigations have been carried out on bis-guanylhydrazone of 1-phenyl-2-chloro-3,7-diformylindole (I) and it was found that its activity is of the order of 1 microgram per ml (Fig. 3). The compound completely blocks low multiplicity infections while it only blocks cytopathogenicity, not viral replication, in high multiplicity infections."}
{"id": "PMID:196935", "title": "[Effect of low molecular weight basic proteins on mannose transport in Aspergillus niger microsomes].", "content": "Basic proteins of low molecular weight activate the transfer of mannose to endogenous glycoprotein acceptors in microsomal membranes of Aspergillus niger. The enhancement of mannosyltransferase activity is linked to the activation of the transport of mannose across the membrane. The role of these polycationic proteins on the membrane permeability is discussed.", "contents": "[Effect of low molecular weight basic proteins on mannose transport in Aspergillus niger microsomes]. Basic proteins of low molecular weight activate the transfer of mannose to endogenous glycoprotein acceptors in microsomal membranes of Aspergillus niger. The enhancement of mannosyltransferase activity is linked to the activation of the transport of mannose across the membrane. The role of these polycationic proteins on the membrane permeability is discussed."}
{"id": "PMID:196941", "title": "Cholinergic, adrenergic, and purinergic neuromuscular transmission.", "content": "A general model of the autonomic neuromuscular junction is proposed which emphasizes muscle effector bundles with gap junctions (or 'nexuses') forming the low resistance pathways allowing electrotonic coupling between neighboring cells, and extensive terminal varicose nerve fibers with 'en passage' release of transmitter. Some variations in autonomic neuromuscular geometry are discussed. Junctional clefts vary from 15nm in densely-innervated tissues such as vas deferens and iris to 2,000 nm in some large elastic arteries. Postjunctional specializations take the form of subsynaptic cysternae (in vas deferens and iris) and aggregations of plasmalemmal vesicles (in circular intestinal muscle). Current views of the synthesis, storage, release, and inactivation of transmitter during cholinergic, adrenergic, and purinergic transmission are summarized.", "contents": "Cholinergic, adrenergic, and purinergic neuromuscular transmission. A general model of the autonomic neuromuscular junction is proposed which emphasizes muscle effector bundles with gap junctions (or 'nexuses') forming the low resistance pathways allowing electrotonic coupling between neighboring cells, and extensive terminal varicose nerve fibers with 'en passage' release of transmitter. Some variations in autonomic neuromuscular geometry are discussed. Junctional clefts vary from 15nm in densely-innervated tissues such as vas deferens and iris to 2,000 nm in some large elastic arteries. Postjunctional specializations take the form of subsynaptic cysternae (in vas deferens and iris) and aggregations of plasmalemmal vesicles (in circular intestinal muscle). Current views of the synthesis, storage, release, and inactivation of transmitter during cholinergic, adrenergic, and purinergic transmission are summarized."}
{"id": "PMID:196944", "title": "Modulation of smooth muscle activity by catecholamines.", "content": "The inhibitory and excitatory actions of catecholamines are compared in various types of smooth muscle. Inhibition is usually but not invariably associated with membrane hyperpolarization and a decrease in membrane resistance. It also has a metabolic component frequently involving an increase in tissue cAMP. In some cases, the metabolic component is related to a cation pump, but the nature of this pump is unclear. With the exception of intestinal muscle where inhibition results from the synergistic action of alpha and beta receptors, inhibition is caused by activation of beta receptors. Excitation is mediated by alpha activation and is usually accompanied by a decrease in membrane potential and membrane resistance. Only the uterus has a metabolic component. The specific ionic permeability changes accompanying excitation are different in various smooth muscles. Clarification of the mechanisms responsible for these differential actions in various types of smooth muscle is a challenge for future work.", "contents": "Modulation of smooth muscle activity by catecholamines. The inhibitory and excitatory actions of catecholamines are compared in various types of smooth muscle. Inhibition is usually but not invariably associated with membrane hyperpolarization and a decrease in membrane resistance. It also has a metabolic component frequently involving an increase in tissue cAMP. In some cases, the metabolic component is related to a cation pump, but the nature of this pump is unclear. With the exception of intestinal muscle where inhibition results from the synergistic action of alpha and beta receptors, inhibition is caused by activation of beta receptors. Excitation is mediated by alpha activation and is usually accompanied by a decrease in membrane potential and membrane resistance. Only the uterus has a metabolic component. The specific ionic permeability changes accompanying excitation are different in various smooth muscles. Clarification of the mechanisms responsible for these differential actions in various types of smooth muscle is a challenge for future work."}
{"id": "PMID:196946", "title": "[Effect of several catecholamines on pulmonary circulation].", "content": "In anesthetized dogs, i. v. injections of 0.1-1.0 mcg/kg adrenaline, noradrenaline, and isadrine evoked a raise of blood pressure in the right ventricle of the hear by 13-200%. The greatest pressor effects were obtained with isadrine, the smallest those--with noradrenaline. In experiments with closed chest animals with perfusion of lungs lobe by venous blood under constant pressure and recording of blood flow with photoelectric drop recorder, injections into perfusate of 0.02-32.0 mcg adrenaline and noradrenaline diminished blood flow and increased vascular resistance. In 1/3 of cases isadrine evoked the same reaction, in other cases it increased blood flow in perfused lobe and decreased resistance. The isadrine effect was blocked by beta--blocking agent inderal, whereas those of adrenaline and noradrenaline--by alpha-blocking drug phentolamine. Adrenaline and noradrenaline to constrict the pulmonary vessels by activating the vascular alpha-adrenoreceptors. Isadrine can dilate and constrict the lung vessels. In intact circulation isadrine seems to cause vasoconstriction and elevate blood pressure in lesser circulation.", "contents": "[Effect of several catecholamines on pulmonary circulation]. In anesthetized dogs, i. v. injections of 0.1-1.0 mcg/kg adrenaline, noradrenaline, and isadrine evoked a raise of blood pressure in the right ventricle of the hear by 13-200%. The greatest pressor effects were obtained with isadrine, the smallest those--with noradrenaline. In experiments with closed chest animals with perfusion of lungs lobe by venous blood under constant pressure and recording of blood flow with photoelectric drop recorder, injections into perfusate of 0.02-32.0 mcg adrenaline and noradrenaline diminished blood flow and increased vascular resistance. In 1/3 of cases isadrine evoked the same reaction, in other cases it increased blood flow in perfused lobe and decreased resistance. The isadrine effect was blocked by beta--blocking agent inderal, whereas those of adrenaline and noradrenaline--by alpha-blocking drug phentolamine. Adrenaline and noradrenaline to constrict the pulmonary vessels by activating the vascular alpha-adrenoreceptors. Isadrine can dilate and constrict the lung vessels. In intact circulation isadrine seems to cause vasoconstriction and elevate blood pressure in lesser circulation."}
{"id": "PMID:196947", "title": "[Role of ACTH and glucocorticoids in providing for non-enzymatic fibrinolysis in animals under immobilization stress].", "content": "The 30-min immobilization stress was shown to raise significantly the non-enzymatic fibrinolytic activity of blood in rats. Combined with ACTH the effect is still greater. I. v. administration of 0.2 ml 0.01% solution of protaiminsulphate prevented the non-enzymatic fibrinolysis induced by the stress. Administration of ACTH after proteminsulphate again raised the fibrinolysis. This suggests that ACTH stimulates release of heparin. As the hydrocortisone administration proved ineffective, the stimulating effect of ACTH seems to have no relation to activation of glycocorticoids secretion. Glycocorticoids in this case appear to have a permissive role. This is corroborated by the data obtained with administration of protaminsulphate in 48 hrs after adrenalectomy. Neither ACTH nor hydrocortisone separately stimulated the non-enzymatic fibrinolysis in these animals. This process can be normalized in adrenalectomized animals with combined ACTH and hydrocortisone.", "contents": "[Role of ACTH and glucocorticoids in providing for non-enzymatic fibrinolysis in animals under immobilization stress]. The 30-min immobilization stress was shown to raise significantly the non-enzymatic fibrinolytic activity of blood in rats. Combined with ACTH the effect is still greater. I. v. administration of 0.2 ml 0.01% solution of protaiminsulphate prevented the non-enzymatic fibrinolysis induced by the stress. Administration of ACTH after proteminsulphate again raised the fibrinolysis. This suggests that ACTH stimulates release of heparin. As the hydrocortisone administration proved ineffective, the stimulating effect of ACTH seems to have no relation to activation of glycocorticoids secretion. Glycocorticoids in this case appear to have a permissive role. This is corroborated by the data obtained with administration of protaminsulphate in 48 hrs after adrenalectomy. Neither ACTH nor hydrocortisone separately stimulated the non-enzymatic fibrinolysis in these animals. This process can be normalized in adrenalectomized animals with combined ACTH and hydrocortisone."}
{"id": "PMID:196948", "title": "[Effect of beta-adrenoreceptor blockade on cerebral circulation and extracranial vascular tone].", "content": "The influence of anapriline (propranolol) on the cerebral circulation rate, tone of the cerebral and femural vessels, pO2 in the cerebral tissue, was studied. I. v. administration of anapriline decreased the arterial blood pressure. The changes of tone of the vessels are often of the two-phase character: a decrease followed by an increase. The lowering of the arterial pressure is the most probable cause of the lowering cerebral circulation rate. pO2 decreases accordingly to the blood flow. The effect of anapriline was greater in anesthetized animals.", "contents": "[Effect of beta-adrenoreceptor blockade on cerebral circulation and extracranial vascular tone]. The influence of anapriline (propranolol) on the cerebral circulation rate, tone of the cerebral and femural vessels, pO2 in the cerebral tissue, was studied. I. v. administration of anapriline decreased the arterial blood pressure. The changes of tone of the vessels are often of the two-phase character: a decrease followed by an increase. The lowering of the arterial pressure is the most probable cause of the lowering cerebral circulation rate. pO2 decreases accordingly to the blood flow. The effect of anapriline was greater in anesthetized animals."}
{"id": "PMID:196966", "title": "The acro-renal syndrome of Curran.", "content": "A nine-year-old girl with symmetrical acral deformities and anomalies of the renal tract is described. There have been four previous reports of this association, all in phenotypic males. In each case there was moderate intellectual retardation and in two cases dermatoglyphic analysis revealed abnormalities. It is suggested that there is now sufficient evidence to give the acro-renal syndrome independent status.", "contents": "The acro-renal syndrome of Curran. A nine-year-old girl with symmetrical acral deformities and anomalies of the renal tract is described. There have been four previous reports of this association, all in phenotypic males. In each case there was moderate intellectual retardation and in two cases dermatoglyphic analysis revealed abnormalities. It is suggested that there is now sufficient evidence to give the acro-renal syndrome independent status."}
{"id": "PMID:196968", "title": "Search for infectious Epstein-Barr virus-releasing cell lines, with particular reference to a new producer line, NHAd-60.", "content": "In a search for infectious Epstein-Barr virus (EBV)-producer cell sources, 36 EBV genome-carrying lymphoblastoid cell lines originating from various sources in Japan were screened. Three cell lines derived from different sources were found to release infectious EBV into the culture fluid. EBV from these 3 lines possessed leucocyte-transformation activity but did not induce early antigen formation. One of the three lines, NHAd-60, originated from an adenoid tissue; it released a relatively large amount of infectious virus (10(2) to 10(3) of 50% of transforming dose of cord leucocytes). The NHAd-60 virus strain was further characterized. Cellular, virological, and immunological properties were described and discussed, and compared with EBV from known producer cell lines.", "contents": "Search for infectious Epstein-Barr virus-releasing cell lines, with particular reference to a new producer line, NHAd-60. In a search for infectious Epstein-Barr virus (EBV)-producer cell sources, 36 EBV genome-carrying lymphoblastoid cell lines originating from various sources in Japan were screened. Three cell lines derived from different sources were found to release infectious EBV into the culture fluid. EBV from these 3 lines possessed leucocyte-transformation activity but did not induce early antigen formation. One of the three lines, NHAd-60, originated from an adenoid tissue; it released a relatively large amount of infectious virus (10(2) to 10(3) of 50% of transforming dose of cord leucocytes). The NHAd-60 virus strain was further characterized. Cellular, virological, and immunological properties were described and discussed, and compared with EBV from known producer cell lines."}
{"id": "PMID:196969", "title": "Suggestive evidence for relationship between sensitivity and repair capability in rat ascites hepatoma cells treated with the antitumor agent, 1-(gamma-chloropropyl)-2-chloromethylpiperidine hydrobromide.", "content": "Antitumor activity of 1-(gamma-chloropropyl)-2-chloromethylpiperidine hydrobromide (CAP-2) was studied in vivo and in vitro, using various rat ascites hepatoma cell lines. Among eight ascites hepatoma cell lines, AH-13 was extremely sensitive both to in vivo antitumor and to in vitro lethal action of the agent, whereas AH-44 was resistant in both cases. The sensitivity of ascites hepatoma cell lines to CAP-2, nitrogen mustard N-oxide, 4-nitroquinoline 1-oxide, and ultraviolet ray in vitro was widely different but their relative sensitivities were very similar against these agents. For all the agents, AH-13 was inactivated very rapidly and AH-109A moderately, whereas AH-44 was relatively resistant. These results indicate that the sensitivity of the cells to CAP-2 may be closely related to their repair-capability of damaged DNA. Similar experiments using various DNA repair-deficient mutants of Escherichia coli B strain demonstrated that the repair-deficient mutants were several times more sensitive to CAP-2 than the wild type strain. From these results, it may be concluded that CAP-2 induces DNA lesions repairable by the same repair mechanisms that work on pyrimidine dimers.", "contents": "Suggestive evidence for relationship between sensitivity and repair capability in rat ascites hepatoma cells treated with the antitumor agent, 1-(gamma-chloropropyl)-2-chloromethylpiperidine hydrobromide. Antitumor activity of 1-(gamma-chloropropyl)-2-chloromethylpiperidine hydrobromide (CAP-2) was studied in vivo and in vitro, using various rat ascites hepatoma cell lines. Among eight ascites hepatoma cell lines, AH-13 was extremely sensitive both to in vivo antitumor and to in vitro lethal action of the agent, whereas AH-44 was resistant in both cases. The sensitivity of ascites hepatoma cell lines to CAP-2, nitrogen mustard N-oxide, 4-nitroquinoline 1-oxide, and ultraviolet ray in vitro was widely different but their relative sensitivities were very similar against these agents. For all the agents, AH-13 was inactivated very rapidly and AH-109A moderately, whereas AH-44 was relatively resistant. These results indicate that the sensitivity of the cells to CAP-2 may be closely related to their repair-capability of damaged DNA. Similar experiments using various DNA repair-deficient mutants of Escherichia coli B strain demonstrated that the repair-deficient mutants were several times more sensitive to CAP-2 than the wild type strain. From these results, it may be concluded that CAP-2 induces DNA lesions repairable by the same repair mechanisms that work on pyrimidine dimers."}
{"id": "PMID:196971", "title": "Geographical distribution of the subtype of hepatitis B surface antigen in Chinese.", "content": "Using the much more sensitive hemagglutination inhibition assay for subtyping of hepatitis B surface antigen (HBsAg), we examined the determinants a, d, w and r in 192 from 228 HBsAg positive adults who had been found after screening with reversed passive hemagglutination method. Sixty-four subtypable cases were asymptomatic carriers and the remaining 128 were liver disease patients. Among them there was no significant difference of the subtypes, invariably with adw as the main subtype. Geographical difference was evident: adr was the main subtype (78 per cent) among the northern Chinese; while adw was dominant (76 per cent) among the southern Chinese with the Yangtze River as a boundary. Eight of the 18 adr-subtyped northern Chinese were born and live in Taiwan where 91 per cent of HBsAg positive Taiwanese were adw-subtyped. This was an indirect evidence that intra-familial spreading from parents played an important role in hepatitis B virus infection.", "contents": "Geographical distribution of the subtype of hepatitis B surface antigen in Chinese. Using the much more sensitive hemagglutination inhibition assay for subtyping of hepatitis B surface antigen (HBsAg), we examined the determinants a, d, w and r in 192 from 228 HBsAg positive adults who had been found after screening with reversed passive hemagglutination method. Sixty-four subtypable cases were asymptomatic carriers and the remaining 128 were liver disease patients. Among them there was no significant difference of the subtypes, invariably with adw as the main subtype. Geographical difference was evident: adr was the main subtype (78 per cent) among the northern Chinese; while adw was dominant (76 per cent) among the southern Chinese with the Yangtze River as a boundary. Eight of the 18 adr-subtyped northern Chinese were born and live in Taiwan where 91 per cent of HBsAg positive Taiwanese were adw-subtyped. This was an indirect evidence that intra-familial spreading from parents played an important role in hepatitis B virus infection."}
{"id": "PMID:196972", "title": "Acrodermatitis enteropathica, zinc, and the Paneth cell. A case report with family studies.", "content": "An infant with acrodermatitis enteropathica was studied before and after starting zinc therapy. Clinical recovery was rapid, and the plasma zinc, serum and mucosal alkaline phosphatase activities returned to normal. Light microscopy of small intestinal biopsies showed normal mucosa. Electron microscopy of the Paneth cells initially revealed abnormal inclusion bodies which disappeared during therapy, suggesting that the abnormality is secondary to zinc deficiency, and not a primary defect. These abnormal inclusions may represent altered secretory granules and a proliferation of lysosomes. We were unable to define the heterozygous state biochemically or histologically.", "contents": "Acrodermatitis enteropathica, zinc, and the Paneth cell. A case report with family studies. An infant with acrodermatitis enteropathica was studied before and after starting zinc therapy. Clinical recovery was rapid, and the plasma zinc, serum and mucosal alkaline phosphatase activities returned to normal. Light microscopy of small intestinal biopsies showed normal mucosa. Electron microscopy of the Paneth cells initially revealed abnormal inclusion bodies which disappeared during therapy, suggesting that the abnormality is secondary to zinc deficiency, and not a primary defect. These abnormal inclusions may represent altered secretory granules and a proliferation of lysosomes. We were unable to define the heterozygous state biochemically or histologically."}
{"id": "PMID:196974", "title": "Effect of adrenocorticotropic hormone on pure exocrine pancreatic secretion in man.", "content": "The effect of adrenocorticotropic hormone (ACTH) on pure exocrine pancreatic secretion was studied in 7 subjects with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery. Intravenous injection of 0.25 mg of ACTH during a prolonged intravenous infusion of secretin (0.5 clinical units per kg-hr) plus cholecystokinin (0.5 Ivy dog units per kg-hr) significantly reduced protein and lipase (both concentration and output) without affecting volume and bicarbonate secretion. The reduction appeared soon after ACTH injection (peak inhibition in the first 15-min period) and lasted about 75 min. The adrenocortical response to ACTH reached its peak at the 60th min. The mechanism by which the pituitary hormone selectively inhibits pancreatic enzyme secretion without affecting volume and bicarbonate remains to be clarified.", "contents": "Effect of adrenocorticotropic hormone on pure exocrine pancreatic secretion in man. The effect of adrenocorticotropic hormone (ACTH) on pure exocrine pancreatic secretion was studied in 7 subjects with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery. Intravenous injection of 0.25 mg of ACTH during a prolonged intravenous infusion of secretin (0.5 clinical units per kg-hr) plus cholecystokinin (0.5 Ivy dog units per kg-hr) significantly reduced protein and lipase (both concentration and output) without affecting volume and bicarbonate secretion. The reduction appeared soon after ACTH injection (peak inhibition in the first 15-min period) and lasted about 75 min. The adrenocortical response to ACTH reached its peak at the 60th min. The mechanism by which the pituitary hormone selectively inhibits pancreatic enzyme secretion without affecting volume and bicarbonate remains to be clarified."}
{"id": "PMID:196977", "title": "[Resistance of a line of Djungarian hamster cells to 6-mercaptopurine].", "content": "A cell line resistant to 6-mercaptopurine (6-MP) is isolated from Djungarian hamster embryonic fibroblasts transformed with SV-40, 6-MP resistance is due to the absence or complete inhibition of GGPRT activity. Initial and resistant cell cultures are similar in the growth rate and in the inoculation efficiency. Caryological analysis (differential chromosome staining--S-bands) revealed considerable caryotype rearrangements in both resistant and sensitive lines as compared with Djungarian hamster normal chromosome set, and also the appearance of specific chromosome markers.", "contents": "[Resistance of a line of Djungarian hamster cells to 6-mercaptopurine]. A cell line resistant to 6-mercaptopurine (6-MP) is isolated from Djungarian hamster embryonic fibroblasts transformed with SV-40, 6-MP resistance is due to the absence or complete inhibition of GGPRT activity. Initial and resistant cell cultures are similar in the growth rate and in the inoculation efficiency. Caryological analysis (differential chromosome staining--S-bands) revealed considerable caryotype rearrangements in both resistant and sensitive lines as compared with Djungarian hamster normal chromosome set, and also the appearance of specific chromosome markers."}
{"id": "PMID:196979", "title": "[Identification of the mink alpha2-lipoprotein Lpm-allotypes by the method of preparatory ultracentrifugation].", "content": "The density class accessory of 8 mink alpha2-lipoprotein allotypes are determined by means of preparative ultracentrifugation. It is found that Lpm1, Lpm2, Lpm2, Lpm3, Lpm4, Lpm5, Lpm7 and Lpm8 are determinants of lipoproteins with density exceeding 1.210, i.e. they are VHDL. The allotypic marker 6, which has been earlier assigned by other criteria to Lpm group, belongs to mink lipoprotein, which distributes during ultracentrifugation at the region of low and, partially, high density.", "contents": "[Identification of the mink alpha2-lipoprotein Lpm-allotypes by the method of preparatory ultracentrifugation]. The density class accessory of 8 mink alpha2-lipoprotein allotypes are determined by means of preparative ultracentrifugation. It is found that Lpm1, Lpm2, Lpm2, Lpm3, Lpm4, Lpm5, Lpm7 and Lpm8 are determinants of lipoproteins with density exceeding 1.210, i.e. they are VHDL. The allotypic marker 6, which has been earlier assigned by other criteria to Lpm group, belongs to mink lipoprotein, which distributes during ultracentrifugation at the region of low and, partially, high density."}
{"id": "PMID:196980", "title": "[Analysis of mutations induced by alkylating compounds in Drosophila sperm. I. Character of visible changes induced by N-nitrosoethylurea and ethylmethanesulfonate in a succession of Drosophila generations].", "content": "Newly appearing hereditary traits were observed in several generations of Drosophila melanogaster: changes in eye and body colour, wing shape, number and shape of chaetae. The results obtained may be interpreted as the evidence for the realization of potential changes induced by NEU and EMS into visible mutations during 1-4th generations. X-irradiation (at a dose of 1000 r) of males from the first generation did not affect the realization of long-living potential changes induced by NEU.", "contents": "[Analysis of mutations induced by alkylating compounds in Drosophila sperm. I. Character of visible changes induced by N-nitrosoethylurea and ethylmethanesulfonate in a succession of Drosophila generations]. Newly appearing hereditary traits were observed in several generations of Drosophila melanogaster: changes in eye and body colour, wing shape, number and shape of chaetae. The results obtained may be interpreted as the evidence for the realization of potential changes induced by NEU and EMS into visible mutations during 1-4th generations. X-irradiation (at a dose of 1000 r) of males from the first generation did not affect the realization of long-living potential changes induced by NEU."}
{"id": "PMID:196983", "title": "Syndactyly--a review and long term results.", "content": "Syndactyly is classified and the principles of its surgical treatment discussed. The notes of eighty-five patients who had 222 webs between them were reviewed. A long term follow-up was carried out on thirty-two of these patients who had seventy-six clefts separated. The sexual and anatomical distribution of the syndactyly was investigated. The results of surgery were assessed including complications, and the relationship of complications to the type of graft used and the age at operation. It is suggested that complicated syndactyly is often separated at too early an age.", "contents": "Syndactyly--a review and long term results. Syndactyly is classified and the principles of its surgical treatment discussed. The notes of eighty-five patients who had 222 webs between them were reviewed. A long term follow-up was carried out on thirty-two of these patients who had seventy-six clefts separated. The sexual and anatomical distribution of the syndactyly was investigated. The results of surgery were assessed including complications, and the relationship of complications to the type of graft used and the age at operation. It is suggested that complicated syndactyly is often separated at too early an age."}
{"id": "PMID:196984", "title": "[Lymphography in malignant ovarian tumours (author's transl)].", "content": "21% of 81 patients with malignant neoplasms of the ovaries had lymphographic evidence of metastases in regional iliac and aortic lymph nodes. The frequency of lymphatic metastases in various stages was approximately the same (FIGO stage I = 17%, II = 21%, III = 19%). About one fifth of patients therefore had to be restaged. Lymphography should be used for staging routinely, even if a laparotomy is planned.", "contents": "[Lymphography in malignant ovarian tumours (author's transl)]. 21% of 81 patients with malignant neoplasms of the ovaries had lymphographic evidence of metastases in regional iliac and aortic lymph nodes. The frequency of lymphatic metastases in various stages was approximately the same (FIGO stage I = 17%, II = 21%, III = 19%). About one fifth of patients therefore had to be restaged. Lymphography should be used for staging routinely, even if a laparotomy is planned."}
{"id": "PMID:196985", "title": "Limitations of angiographic differential diagnosis in major hepatic processes.", "content": "In 11 instances (6%) of 183 consecutive hepatic angiograms done for subsequently proven pathologic hepatic processes, either the diagnosis was incorrect (4 patients) or a satisfactory differential diagnosis was not established (7 patients), despite obvious angiographic abnormalities. Incorrect diagnoses were made in patients with suppurative hapatocarcinoma and liver cyst, macronodular regenerative cirrhosis, and multiple intrahepatic abscesses. Satisfactory differential diagnoses could not be established in patients with enlarged intrahepatic ducts, acute viral hepatitis, recurrent cirrhosis and acute liver necrosis. On analysis, means for minimizing diagnostic failure include the use of enhancement techniques such as infusion angiography and pharmacoangiography and an unbiased, detailed analysis of the angiographic findings. Changes secondary to the pathologic process and the coexistence of multiple processes, however, can occasionally prevent an accurate diagnosis.", "contents": "Limitations of angiographic differential diagnosis in major hepatic processes. In 11 instances (6%) of 183 consecutive hepatic angiograms done for subsequently proven pathologic hepatic processes, either the diagnosis was incorrect (4 patients) or a satisfactory differential diagnosis was not established (7 patients), despite obvious angiographic abnormalities. Incorrect diagnoses were made in patients with suppurative hapatocarcinoma and liver cyst, macronodular regenerative cirrhosis, and multiple intrahepatic abscesses. Satisfactory differential diagnoses could not be established in patients with enlarged intrahepatic ducts, acute viral hepatitis, recurrent cirrhosis and acute liver necrosis. On analysis, means for minimizing diagnostic failure include the use of enhancement techniques such as infusion angiography and pharmacoangiography and an unbiased, detailed analysis of the angiographic findings. Changes secondary to the pathologic process and the coexistence of multiple processes, however, can occasionally prevent an accurate diagnosis."}
{"id": "PMID:196986", "title": "[Angiographic findings in benign liver tumours (author's transl)].", "content": "Difficulties in the differential diagnosis of benign liver tumours and their differentiation from malignant liver tumours are discussed. Two patients with benign lesions were described, one with a liver cell adenoma, the other with a mixed cholangiohepato-adenoma (local nodular hyperplasia).", "contents": "[Angiographic findings in benign liver tumours (author's transl)]. Difficulties in the differential diagnosis of benign liver tumours and their differentiation from malignant liver tumours are discussed. Two patients with benign lesions were described, one with a liver cell adenoma, the other with a mixed cholangiohepato-adenoma (local nodular hyperplasia)."}
{"id": "PMID:196987", "title": "[Angiography and differential diagnosis of malignant liver cell tumours (author's transl)].", "content": "The angiographic appearances of malignant liver cell tumours are described. The differential diagnosis between hepatoblastomas and hepatocellular carcinoma is discussed with reference to ten patients seen by the authors, the difference depending on the maturity of the liver tissue undergoing malignant change.", "contents": "[Angiography and differential diagnosis of malignant liver cell tumours (author's transl)]. The angiographic appearances of malignant liver cell tumours are described. The differential diagnosis between hepatoblastomas and hepatocellular carcinoma is discussed with reference to ten patients seen by the authors, the difference depending on the maturity of the liver tissue undergoing malignant change."}
{"id": "PMID:196988", "title": "[Limitations in the internistic treatment of ulcerative colitis and Crohn's disease].", "content": "Aetiology of ulcerative colitis and Crohn's disease is unknown. Therefore causal therapy is not possible. Conservative treatment for both diseases is of antiinflammatory, symptomatic and substituting nature. Surgical intervention is indicated if conservative treatment fails or if dangerous complications occur. The right moment for an operation can only be determined in close cooperation between internist and surgeon.", "contents": "[Limitations in the internistic treatment of ulcerative colitis and Crohn's disease]. Aetiology of ulcerative colitis and Crohn's disease is unknown. Therefore causal therapy is not possible. Conservative treatment for both diseases is of antiinflammatory, symptomatic and substituting nature. Surgical intervention is indicated if conservative treatment fails or if dangerous complications occur. The right moment for an operation can only be determined in close cooperation between internist and surgeon."}
{"id": "PMID:196989", "title": "Effect of hyperthermia on epididymal cyclic AMP levels in diabetic non-diabetic and hypophysectomized rats.", "content": "The effect of elevated body temperatures on the concentrations of epididymal cyclic AMP levels in non-diabetic, diabetic and hypophysectomized rats was studied. Cyclic AMP levels were increased during hyperthermia in all animals examined. This increase in epididymal cyclic AMP concentration was not seen in animals that had been supplemented with exogenous insulin prior to the experiment. The effect of pituitary lipolytic hormones on epididymal cyclic AMP levels was also investigated. Significant elevations of epididymal cyclic AMP levels were observed in hypophysectomized rats during hyperthermia indicating that pituitary hormones are not essential in causing these increases. Extrapituitary hormones, such as glucagon, might be responsible for epididymal cyclic AMP increases. Increases in epididymal cyclic AMP levels may therefore be the result of the reduction of blood insulin and concomitant increases of lipolytic hormones of both pituitary and extrapituitary origins.", "contents": "Effect of hyperthermia on epididymal cyclic AMP levels in diabetic non-diabetic and hypophysectomized rats. The effect of elevated body temperatures on the concentrations of epididymal cyclic AMP levels in non-diabetic, diabetic and hypophysectomized rats was studied. Cyclic AMP levels were increased during hyperthermia in all animals examined. This increase in epididymal cyclic AMP concentration was not seen in animals that had been supplemented with exogenous insulin prior to the experiment. The effect of pituitary lipolytic hormones on epididymal cyclic AMP levels was also investigated. Significant elevations of epididymal cyclic AMP levels were observed in hypophysectomized rats during hyperthermia indicating that pituitary hormones are not essential in causing these increases. Extrapituitary hormones, such as glucagon, might be responsible for epididymal cyclic AMP increases. Increases in epididymal cyclic AMP levels may therefore be the result of the reduction of blood insulin and concomitant increases of lipolytic hormones of both pituitary and extrapituitary origins."}
{"id": "PMID:196990", "title": "Effects of clofibrate on the human fat cell adenylate cyclase system.", "content": "The effects of chlofibrate on the adenylate cyclase system of human adipocytes were studied. Clofibrate reduced basal as well as hormone-NaF)stimulated adenylate cyclase activities to about the same extent (45% inhibition at 1 mg/ml clofibrate). The relative extent of hormonal stimulation was not altered by this compound. The inhibitory action of clofibrate was non-competitive with respect to the substrate ATP and cofactors (Mg2+-ions). Inhibition of enzyme activity was detectable after 2.5 min. Our results suggest that the antilipolytic activity of clofibrate is mediated via inhibition of the catalytic subunit of the fat cell adenylate cyclase.", "contents": "Effects of clofibrate on the human fat cell adenylate cyclase system. The effects of chlofibrate on the adenylate cyclase system of human adipocytes were studied. Clofibrate reduced basal as well as hormone-NaF)stimulated adenylate cyclase activities to about the same extent (45% inhibition at 1 mg/ml clofibrate). The relative extent of hormonal stimulation was not altered by this compound. The inhibitory action of clofibrate was non-competitive with respect to the substrate ATP and cofactors (Mg2+-ions). Inhibition of enzyme activity was detectable after 2.5 min. Our results suggest that the antilipolytic activity of clofibrate is mediated via inhibition of the catalytic subunit of the fat cell adenylate cyclase."}
{"id": "PMID:196992", "title": "Critical evaluation of the 5-day metyrapone test.", "content": "Different parameters of the response to the 5-day metyrapone test were evaluated for their diagnostic accuracy in tests given to 58 children and adolescents as part of an investigation for short stature. Insulin test, vasopressin test and ACTH test were used for diagnostic reference. A log transformation of the data was clearly appropriate. The maximal daily excretion of 17-ketogenic steroids was distinctly positively correlated with the basal excretion. Consequently, the most correct parameter of the response is the SD score of the deviation of the maximal excretion from the regression of the maximal excretion on the basal excretion in the reference population. This parameter, 'relative maximal excretion' was shown to be the diagnostically most accurate index of the response of 11 parameters studied.", "contents": "Critical evaluation of the 5-day metyrapone test. Different parameters of the response to the 5-day metyrapone test were evaluated for their diagnostic accuracy in tests given to 58 children and adolescents as part of an investigation for short stature. Insulin test, vasopressin test and ACTH test were used for diagnostic reference. A log transformation of the data was clearly appropriate. The maximal daily excretion of 17-ketogenic steroids was distinctly positively correlated with the basal excretion. Consequently, the most correct parameter of the response is the SD score of the deviation of the maximal excretion from the regression of the maximal excretion on the basal excretion in the reference population. This parameter, 'relative maximal excretion' was shown to be the diagnostically most accurate index of the response of 11 parameters studied."}
{"id": "PMID:196993", "title": "Iodinated bovine prolactin. Characterization and binding to mammary gland cells.", "content": "Iodinated bovine prolactin (2.6 iodine atoms/molecule; labelled with a trace of 125I to give a specific activity of 0.041 muCi/mg) was prepared by the chloramine T method. It was active in two bioassays (pigeon crop sac and dispersed mouse mammary cell), though somewhat less active than the unmodified hormone. In an immunoassay, iodinated prolactin was more effective than the unmodified hormone at displacing 125I-prolactin from antibody. High specific activity 125I-prolactin (1 iodine atom/molecule; 70 muCi/microgram) was used for autoradiographic studies on the binding of prolactin to mouse mammary cells. In vivo the labelled hormone found in the mammary gland was associated with membranes of mammary epithelial cells and with alveolar lumen contents. In vitro 125I-prolactin was shown to bind to dispersed mouse mammary epithelial cells.", "contents": "Iodinated bovine prolactin. Characterization and binding to mammary gland cells. Iodinated bovine prolactin (2.6 iodine atoms/molecule; labelled with a trace of 125I to give a specific activity of 0.041 muCi/mg) was prepared by the chloramine T method. It was active in two bioassays (pigeon crop sac and dispersed mouse mammary cell), though somewhat less active than the unmodified hormone. In an immunoassay, iodinated prolactin was more effective than the unmodified hormone at displacing 125I-prolactin from antibody. High specific activity 125I-prolactin (1 iodine atom/molecule; 70 muCi/microgram) was used for autoradiographic studies on the binding of prolactin to mouse mammary cells. In vivo the labelled hormone found in the mammary gland was associated with membranes of mammary epithelial cells and with alveolar lumen contents. In vitro 125I-prolactin was shown to bind to dispersed mouse mammary epithelial cells."}
{"id": "PMID:196995", "title": "Immobilized Clostridium perfringens neuraminidase. Substrate cleavage and enzyme release during incubation.", "content": "Pure Clostridium perfringens neuraminidase was immobilized on Sepharose 4 B, azido-Sepharose 4 B and controlled pore glass (CPG)- glycophase using different coupling procedures. The immobilized enzyme showed increased stability under various conditions relative to the soluble enzyme. The low release of active enzyme from the supports under incubation conditions was quantitated using a highly sensitive radioactive assay. The activity of the immobilized enzyme was dependent on the nature of the support and the substrate. Activity decreased with increasing substrate molecular weight, but the enzyme showed improved cleavage with GD1a micelles and human erythrocytes, substrates having ordered surface properties. Uses of immobilized neuraminidase in biochemistry and cell biology are considered and evaluated relative to the measured release of enzyme from the supports reported and to the molecular size and organization of possible substrates.", "contents": "Immobilized Clostridium perfringens neuraminidase. Substrate cleavage and enzyme release during incubation. Pure Clostridium perfringens neuraminidase was immobilized on Sepharose 4 B, azido-Sepharose 4 B and controlled pore glass (CPG)- glycophase using different coupling procedures. The immobilized enzyme showed increased stability under various conditions relative to the soluble enzyme. The low release of active enzyme from the supports under incubation conditions was quantitated using a highly sensitive radioactive assay. The activity of the immobilized enzyme was dependent on the nature of the support and the substrate. Activity decreased with increasing substrate molecular weight, but the enzyme showed improved cleavage with GD1a micelles and human erythrocytes, substrates having ordered surface properties. Uses of immobilized neuraminidase in biochemistry and cell biology are considered and evaluated relative to the measured release of enzyme from the supports reported and to the molecular size and organization of possible substrates."}
{"id": "PMID:196996", "title": "Infectious mononucleosis: recognition and management.", "content": "Differentiation from other common viral infections depends on a triad of clinical, hematologic, and serologic determinations. A distinctive feature is that while a number of circulating immunoglobulins are often detected, only Paul-Bunnell antibodies, found in 75% of cases, are specific for IM. Symptomatic care only is indicated for most patients, though severe cases or complications may require antibiotics or corticosteroids.", "contents": "Infectious mononucleosis: recognition and management. Differentiation from other common viral infections depends on a triad of clinical, hematologic, and serologic determinations. A distinctive feature is that while a number of circulating immunoglobulins are often detected, only Paul-Bunnell antibodies, found in 75% of cases, are specific for IM. Symptomatic care only is indicated for most patients, though severe cases or complications may require antibiotics or corticosteroids."}
{"id": "PMID:196998", "title": "Sclerosing hemangioma of the lung: an endothelial or epithelial neoplasm?", "content": "The ultrastructural features of a sclerosing hemangioma of the lung in a 34 year old woman are described. The basic cellular response is thought to be endothelial and not epithelial. These conclusions are based on the finding of Weibel-Palade bodies within the tumor cells in addition to other characteristics generally associated with endothelial cells.", "contents": "Sclerosing hemangioma of the lung: an endothelial or epithelial neoplasm? The ultrastructural features of a sclerosing hemangioma of the lung in a 34 year old woman are described. The basic cellular response is thought to be endothelial and not epithelial. These conclusions are based on the finding of Weibel-Palade bodies within the tumor cells in addition to other characteristics generally associated with endothelial cells."}
{"id": "PMID:197002", "title": "Factors affecting tracheobronchial mucociliary transport.", "content": "In vivo mucus transport rates were studied in humans and donkeys by external measurement of the rate of clearance of insoluble monodisperse gamma-tagged aerosols. The influence of temperature, environmental toxicants and drugs which affect the autonomic nervous system were studied by determining the changes in clearance produced by them in individual subjects. In donkeys, increased pretest ambient temperature accelerated clearance by greater than 1.7%/ degrees C. Smoking 2-7 cigarettes reduced the duration of bronchial clearance by approximately 50% in both humans and donkeys. Donkeys were exposed to higher doses; with progressive slowing of tracheal and bronchial clearance for greater than 10 cigarettes. HCN, at concentrations up to 1230 ppm, produced only a mild transient slowing of clearance. In man, atropine slowed clearance, while the adrenergic stimulating drugs, isoproterenol and epinephrine, both accelerated it by greater than or equal to 4 times, as did isoproterenol when given subsequent to atropine. The cholinergic stimulating drug methacholine increased mucociliary transport in the the donkey. Administration of a tap water aerosol for 10-15 min in humans increased bronchial clearance rates by approximately 25%.", "contents": "Factors affecting tracheobronchial mucociliary transport. In vivo mucus transport rates were studied in humans and donkeys by external measurement of the rate of clearance of insoluble monodisperse gamma-tagged aerosols. The influence of temperature, environmental toxicants and drugs which affect the autonomic nervous system were studied by determining the changes in clearance produced by them in individual subjects. In donkeys, increased pretest ambient temperature accelerated clearance by greater than 1.7%/ degrees C. Smoking 2-7 cigarettes reduced the duration of bronchial clearance by approximately 50% in both humans and donkeys. Donkeys were exposed to higher doses; with progressive slowing of tracheal and bronchial clearance for greater than 10 cigarettes. HCN, at concentrations up to 1230 ppm, produced only a mild transient slowing of clearance. In man, atropine slowed clearance, while the adrenergic stimulating drugs, isoproterenol and epinephrine, both accelerated it by greater than or equal to 4 times, as did isoproterenol when given subsequent to atropine. The cholinergic stimulating drug methacholine increased mucociliary transport in the the donkey. Administration of a tap water aerosol for 10-15 min in humans increased bronchial clearance rates by approximately 25%."}
{"id": "PMID:197003", "title": "Investigations into the determination of the cytotoxicity of quartz dust by physical methods.", "content": "The methods of thermally stimulated luminescence (t.s.l), thermally stimulated exoelectron emission (t.s.e.e.), electron spin resonance (e.s.r), and infrared spectroscopy (i.r.) have been used to investigate whether the specific cytotoxic activities of SiO2 dust of various origins can be attributed to physical parameters. After interaction of toxic dusts with water an increase in the intensity of the t.s.l. peaks below room temperature has been detected whereas no effect could be observed in the case of inert materials. Dusts of weak cytotoxicity have been characterized by infrared absorption bands at 3610 cm-1 and 3685 cm-1. The results of the present studies emphasize the significance of silanol groups and adsorption properties in relation to the fibrogenic activity of quartz dusts.", "contents": "Investigations into the determination of the cytotoxicity of quartz dust by physical methods. The methods of thermally stimulated luminescence (t.s.l), thermally stimulated exoelectron emission (t.s.e.e.), electron spin resonance (e.s.r), and infrared spectroscopy (i.r.) have been used to investigate whether the specific cytotoxic activities of SiO2 dust of various origins can be attributed to physical parameters. After interaction of toxic dusts with water an increase in the intensity of the t.s.l. peaks below room temperature has been detected whereas no effect could be observed in the case of inert materials. Dusts of weak cytotoxicity have been characterized by infrared absorption bands at 3610 cm-1 and 3685 cm-1. The results of the present studies emphasize the significance of silanol groups and adsorption properties in relation to the fibrogenic activity of quartz dusts."}
{"id": "PMID:197004", "title": "Hepatic clearance of Salmonella typhimurium in silica-treated mice.", "content": "Scanning electron microscopy demonstrates that crystalline silica destroys liver Kupffer cells but has no other obvious deleterious effects on the liver. Silica-treated livers still retain the ability to trap large numbers of bacteria perfused through the portal vein even though the rate of clearance is well below normal. In vivo, silica treatment decreases the rate of bacterial clearance from the blood, alters the in vivo organ distribution of cleared bacteria, and decreases the mean lethal dose of Salmonella typhimurium over 100-fold. Cumulatively, the data indicate that silica treatment enhances susceptibility to gram-negative infection, probably by destruction of macrophages.", "contents": "Hepatic clearance of Salmonella typhimurium in silica-treated mice. Scanning electron microscopy demonstrates that crystalline silica destroys liver Kupffer cells but has no other obvious deleterious effects on the liver. Silica-treated livers still retain the ability to trap large numbers of bacteria perfused through the portal vein even though the rate of clearance is well below normal. In vivo, silica treatment decreases the rate of bacterial clearance from the blood, alters the in vivo organ distribution of cleared bacteria, and decreases the mean lethal dose of Salmonella typhimurium over 100-fold. Cumulatively, the data indicate that silica treatment enhances susceptibility to gram-negative infection, probably by destruction of macrophages."}
{"id": "PMID:197005", "title": "Interaction of inflammatory cells and oral microorganisms. IV. In vitro release of lysosomal constituents from polymorphonuclear leukocytes exposed to supragingival and subgingival bacterial plaque.", "content": "The deposition of bacterial plaques on tooth surfaces appears to be responsible for the initiation and progression of periodontal disease. In this study, human peripheral blood polymorphonuclear leukocytes (PMNs) actively released lysosomal constituents upon in vitro exposure to either viable or irradiated, supragingival or subgingival dental plaque. Plaques were obtained from the PMN donors (autologous plaque) or from pooled samples (homologous plaque) secured from patients with periodontal lesions. Fresh sera from PMN donors amplified the release reactions to supragingival and subgingival plaques. Heated (56 degrees C, 30 min) sera also enhanced release reactions, but not as consistently as fresh serum. It was postulated that modulation of PMN release by serum is mediated by complement components and/or antibodies to plaque bacteria. Electron microscopic observations indicated that degranulation and discharge of PMN lysosomal enzymes may be associated with phagocytosis of gram-positive and gram-negative plaque bacteria and with reverse endocytosis of lysosomes from cells contacting relatively large masses of aggregated plaque bacteria. These data suggest that PMN lysosome release in response to plaque may serve as a potential mechanism of tissue injury in the pathogenesis of gingival and periodontal inflammation.", "contents": "Interaction of inflammatory cells and oral microorganisms. IV. In vitro release of lysosomal constituents from polymorphonuclear leukocytes exposed to supragingival and subgingival bacterial plaque. The deposition of bacterial plaques on tooth surfaces appears to be responsible for the initiation and progression of periodontal disease. In this study, human peripheral blood polymorphonuclear leukocytes (PMNs) actively released lysosomal constituents upon in vitro exposure to either viable or irradiated, supragingival or subgingival dental plaque. Plaques were obtained from the PMN donors (autologous plaque) or from pooled samples (homologous plaque) secured from patients with periodontal lesions. Fresh sera from PMN donors amplified the release reactions to supragingival and subgingival plaques. Heated (56 degrees C, 30 min) sera also enhanced release reactions, but not as consistently as fresh serum. It was postulated that modulation of PMN release by serum is mediated by complement components and/or antibodies to plaque bacteria. Electron microscopic observations indicated that degranulation and discharge of PMN lysosomal enzymes may be associated with phagocytosis of gram-positive and gram-negative plaque bacteria and with reverse endocytosis of lysosomes from cells contacting relatively large masses of aggregated plaque bacteria. These data suggest that PMN lysosome release in response to plaque may serve as a potential mechanism of tissue injury in the pathogenesis of gingival and periodontal inflammation."}
{"id": "PMID:197006", "title": "Effect of Staphylococcus aureus delta toxin on Chinese hamster ovary cell morphology and Y-1 adrenal cell morphology and steroidogenesis.", "content": "Since Staphylococcus aureus delta toxin previously had been shown to increase the cyclic adenosine 3',5'-monophosphate (cAMP) content of guinea pig ileum, the effect of delta toxin on such cAMP-mediated responses as morphogenesis and steroidogenesis in cultured tissue cells was examined. In contrast to cholera toxin, delta toxin did not cause spindling of Chinese hamster ovary cells. Unlike adrenocorticotropin or cholera toxin, delta toxin was unable to cause rounding of Y-1 adrenal cells or to promote steroid production by the cells. S. aureus alpha toxin and enterotoxin B were also unable to cause rounding of Y-1 adrenal cells. Omission of Ca2+ from the media still allowed for increased steroid production by adrenocorticotropin but not by delta toxin. Delta toxin at concentrations greater than 10 micrograms/ml did cause lysis of both Chinese hamster ovary and Y-1 adrenal cells. These findings suggest that the increase in intestinal cAMP levels caused by delta toxin is mediated through a mechanism different from that initiated by cholera toxin.", "contents": "Effect of Staphylococcus aureus delta toxin on Chinese hamster ovary cell morphology and Y-1 adrenal cell morphology and steroidogenesis. Since Staphylococcus aureus delta toxin previously had been shown to increase the cyclic adenosine 3',5'-monophosphate (cAMP) content of guinea pig ileum, the effect of delta toxin on such cAMP-mediated responses as morphogenesis and steroidogenesis in cultured tissue cells was examined. In contrast to cholera toxin, delta toxin did not cause spindling of Chinese hamster ovary cells. Unlike adrenocorticotropin or cholera toxin, delta toxin was unable to cause rounding of Y-1 adrenal cells or to promote steroid production by the cells. S. aureus alpha toxin and enterotoxin B were also unable to cause rounding of Y-1 adrenal cells. Omission of Ca2+ from the media still allowed for increased steroid production by adrenocorticotropin but not by delta toxin. Delta toxin at concentrations greater than 10 micrograms/ml did cause lysis of both Chinese hamster ovary and Y-1 adrenal cells. These findings suggest that the increase in intestinal cAMP levels caused by delta toxin is mediated through a mechanism different from that initiated by cholera toxin."}
{"id": "PMID:197007", "title": "Evidence for a mouse pathogenicity locus in certain temperature-sensitive mutants of foot-and-mouth disease virus.", "content": "Serial tissue culture passaging of three foot-and-mouth disease temperature-sensitive mutants demonstrated the stability of their temperature sensitivity and mouse avirulence characteristics. Recovery of mouse-virulent temperature-sensitive viruses after passage of the mutants in mice suggested that these were not covariant expressions of the same locus, but were under the control of different genes.", "contents": "Evidence for a mouse pathogenicity locus in certain temperature-sensitive mutants of foot-and-mouth disease virus. Serial tissue culture passaging of three foot-and-mouth disease temperature-sensitive mutants demonstrated the stability of their temperature sensitivity and mouse avirulence characteristics. Recovery of mouse-virulent temperature-sensitive viruses after passage of the mutants in mice suggested that these were not covariant expressions of the same locus, but were under the control of different genes."}
{"id": "PMID:197008", "title": "Immune response and latent infection after topical treatment of herpes simplex virus infection in hairless mice.", "content": "Treatment of herpes simplex virus (HSV)-infected hairless mice with a 2% phosphonoacetic acid (PAA) ointment prevented the appearance of virus-induced skin lesions and subsequent central nervous system (CNS) involvement. Treatment started 24 h after infection significantly reduced the intensity of the skin lesions and also prevented CNS involvement. After four to six applications of PAA ointment, a moderate skin erythemia developed, followed by scaling and complete healing 7 days after cessation of the treatment. Mice treated early after HSV infection had low or undetectable levels of virus-specific antibodies but were completely resistant to reinfection. Early treatment prevented the development of a latent ganglionic infection, but treatment initiated 24 h after infection could not prevent the establishment of the latent infection. PAA-treated and HSV-infected mice with nondetectable levels of antibodies did not develop, with a single exception, a latent ganglionic infection unpon reinfection. The cell-mediated immune response determined by levels of [14C]thymidine incorporation in Ficoll-Hypaque-purified spleen lymphocytes cultures was low in PAA-treated mice; it increased slightly after challenge infection but was strong in mice that proved to harbor a latent HSV infection in the ganglia.", "contents": "Immune response and latent infection after topical treatment of herpes simplex virus infection in hairless mice. Treatment of herpes simplex virus (HSV)-infected hairless mice with a 2% phosphonoacetic acid (PAA) ointment prevented the appearance of virus-induced skin lesions and subsequent central nervous system (CNS) involvement. Treatment started 24 h after infection significantly reduced the intensity of the skin lesions and also prevented CNS involvement. After four to six applications of PAA ointment, a moderate skin erythemia developed, followed by scaling and complete healing 7 days after cessation of the treatment. Mice treated early after HSV infection had low or undetectable levels of virus-specific antibodies but were completely resistant to reinfection. Early treatment prevented the development of a latent ganglionic infection, but treatment initiated 24 h after infection could not prevent the establishment of the latent infection. PAA-treated and HSV-infected mice with nondetectable levels of antibodies did not develop, with a single exception, a latent ganglionic infection unpon reinfection. The cell-mediated immune response determined by levels of [14C]thymidine incorporation in Ficoll-Hypaque-purified spleen lymphocytes cultures was low in PAA-treated mice; it increased slightly after challenge infection but was strong in mice that proved to harbor a latent HSV infection in the ganglia."}
{"id": "PMID:197009", "title": "Biological characterization of avian osteopetrosis.", "content": "Chicks infected as 12-day-old embryos with an end-point purified derivative of avian myeloblastosis virus developed a rapidly progressive osteopetrosis that manifested within 1 week of hatching. A detailed comparison of osteopetrotic chicks and normal hatchmates revealed the following. (i) Osteopetrotic chicks exhibited a stunting syndrome, growing at a mean rate that was 26% of the control rats. (ii) At autopsy, the mass of the lymphoid organs was reduced, whereas the mass of the heart, pancreas, kidneys, lungs, brain, liver, and bones of osteopetrotic chicks was increased. Edema was likely responsible for most of the increase in organ weight. (iii) Infected chicks exhibited a normochromic, normocytic anemia that was virus dose dependent and was not required for the development of osteopetrosis. (iv) Bone collagen content was normal. (v) Osteopetrotic bone was initially hypomineralized, but later became more fully mineralized. (vi) The concentrations of alpha, beta, and gamma globulins in the plasma were elevated in osteopetrotic chicks, whereas albumin concentration was decreased. (vii) The level of plasma alkaline phosphatase was elevated in osteopetrotic chicks, yet the level of acid phosphatase was unchanged. (viii) Body and bone temperatures were unchanged.", "contents": "Biological characterization of avian osteopetrosis. Chicks infected as 12-day-old embryos with an end-point purified derivative of avian myeloblastosis virus developed a rapidly progressive osteopetrosis that manifested within 1 week of hatching. A detailed comparison of osteopetrotic chicks and normal hatchmates revealed the following. (i) Osteopetrotic chicks exhibited a stunting syndrome, growing at a mean rate that was 26% of the control rats. (ii) At autopsy, the mass of the lymphoid organs was reduced, whereas the mass of the heart, pancreas, kidneys, lungs, brain, liver, and bones of osteopetrotic chicks was increased. Edema was likely responsible for most of the increase in organ weight. (iii) Infected chicks exhibited a normochromic, normocytic anemia that was virus dose dependent and was not required for the development of osteopetrosis. (iv) Bone collagen content was normal. (v) Osteopetrotic bone was initially hypomineralized, but later became more fully mineralized. (vi) The concentrations of alpha, beta, and gamma globulins in the plasma were elevated in osteopetrotic chicks, whereas albumin concentration was decreased. (vii) The level of plasma alkaline phosphatase was elevated in osteopetrotic chicks, yet the level of acid phosphatase was unchanged. (viii) Body and bone temperatures were unchanged."}
{"id": "PMID:197010", "title": "Terminal electron transport in Treponema pallidum.", "content": "Reduced-minus-oxidized difference spectra of sonically treated virulent Treponema pallidum disclosed cytochromes of the b anc c types as well as large amounts of flavoprotein. Difference spectra of the carbon monoxide-binding pigment identified cytochrome o as the terminal oxidase. Physiological reduction of the cytochromes indicated that the cytochrome system was functional and established the capability of T. pallidum for aerobic respiration. The potential significance of these findings is discussed.", "contents": "Terminal electron transport in Treponema pallidum. Reduced-minus-oxidized difference spectra of sonically treated virulent Treponema pallidum disclosed cytochromes of the b anc c types as well as large amounts of flavoprotein. Difference spectra of the carbon monoxide-binding pigment identified cytochrome o as the terminal oxidase. Physiological reduction of the cytochromes indicated that the cytochrome system was functional and established the capability of T. pallidum for aerobic respiration. The potential significance of these findings is discussed."}
{"id": "PMID:197011", "title": "Cellular basis of persistent lymphocytosis in cattle infected with bovine leukemia virus.", "content": "Peripheral blood lymphocytes from 14 cattle infected with the bovine leukemia virus (BLV) and 14 BLV-free cattle were examined by the membrane immunofluorescent antibody technique to detect surface immunoglobulin (S-Ig) and by the erythrocyte-antibody-complement (EAC) rosette test for the detection of complement receptors. Direct comparisons of the percentages of S-Ig-bearing cells and EAC rosette-forming cells in both infected and BLV-free animals showed no evidence for the presence of a substantial population bearing one surface marker but not the other. The data showed that cells with surface markers characteristic of B lymphocytes are responsible for most of the increase in peripheral blood lymphocytes which may accompany BLV infection. The release of infectious BLV and the spontaneous uptake of thymidine by short-term cultured peripheral blood lymphocytes from BLV-infected cattle were also studied. The results indicate that both of these activities are function of B lymphocytes.", "contents": "Cellular basis of persistent lymphocytosis in cattle infected with bovine leukemia virus. Peripheral blood lymphocytes from 14 cattle infected with the bovine leukemia virus (BLV) and 14 BLV-free cattle were examined by the membrane immunofluorescent antibody technique to detect surface immunoglobulin (S-Ig) and by the erythrocyte-antibody-complement (EAC) rosette test for the detection of complement receptors. Direct comparisons of the percentages of S-Ig-bearing cells and EAC rosette-forming cells in both infected and BLV-free animals showed no evidence for the presence of a substantial population bearing one surface marker but not the other. The data showed that cells with surface markers characteristic of B lymphocytes are responsible for most of the increase in peripheral blood lymphocytes which may accompany BLV infection. The release of infectious BLV and the spontaneous uptake of thymidine by short-term cultured peripheral blood lymphocytes from BLV-infected cattle were also studied. The results indicate that both of these activities are function of B lymphocytes."}
{"id": "PMID:197012", "title": "Properties of density gradient-fractionated peripheral blood leukocytes from cattle infected with bovine leukemia virus.", "content": "Discontinuous bovine serum albumin gradients were used to fractionate peripheral blood leukocytes from bovine leukemia virus (BLV)-free and BLV-infected cows. The release of infectious BLV and spontaneous incorporation of [3H]thymidine were not properties of density gradient-fractionated leukocytes from a BLV-free cow. When leukocytes from BLV-infected cattle were fractionated, B lymphocytes which spontaneously incorporated [3H]thymidine could be separated as a distinct subpopulation from B lymphocytes which replicated infectious BLV. Density gradient fractionation of leukocytes from a cow with lymphosarcoma is also reported. A fall in lymphocyte count at the time of tumor development is attributed to the loss of B lymphocytes which spontaneously incorporate [3H]thymidine.", "contents": "Properties of density gradient-fractionated peripheral blood leukocytes from cattle infected with bovine leukemia virus. Discontinuous bovine serum albumin gradients were used to fractionate peripheral blood leukocytes from bovine leukemia virus (BLV)-free and BLV-infected cows. The release of infectious BLV and spontaneous incorporation of [3H]thymidine were not properties of density gradient-fractionated leukocytes from a BLV-free cow. When leukocytes from BLV-infected cattle were fractionated, B lymphocytes which spontaneously incorporated [3H]thymidine could be separated as a distinct subpopulation from B lymphocytes which replicated infectious BLV. Density gradient fractionation of leukocytes from a cow with lymphosarcoma is also reported. A fall in lymphocyte count at the time of tumor development is attributed to the loss of B lymphocytes which spontaneously incorporate [3H]thymidine."}
{"id": "PMID:197013", "title": "Protection from oral herpes simplex virus infection by a nucleic acid-free virus vaccine.", "content": "The effect of immunization with inactivated herpes virus vaccines, including a vaccine free of all nucleic acid, was investigated in a mouse model system. Protection against oral lesions induced by herpes simplex virus type 1 was demonstrated by several criteria: (i) reduction in the incidence and severity of primary oral lesions; (ii) decrease in acute and latent infection of the regional sensory ganglia; and (iii) protection from viral encephalitis and death. The immune response of mice to the vaccine and to subsequent virus challenge was measured by following serum-neutralizing antibody titers.", "contents": "Protection from oral herpes simplex virus infection by a nucleic acid-free virus vaccine. The effect of immunization with inactivated herpes virus vaccines, including a vaccine free of all nucleic acid, was investigated in a mouse model system. Protection against oral lesions induced by herpes simplex virus type 1 was demonstrated by several criteria: (i) reduction in the incidence and severity of primary oral lesions; (ii) decrease in acute and latent infection of the regional sensory ganglia; and (iii) protection from viral encephalitis and death. The immune response of mice to the vaccine and to subsequent virus challenge was measured by following serum-neutralizing antibody titers."}
{"id": "PMID:197014", "title": "Immunoglobulin classes of antibodies in milk of swine after intranasal exposure to pseudorabies virus or transmissible gastroenteritis virus.", "content": "Experiments were conducted to evaluate whether infection of the respiratory tract of pregnant swine with pseudorabies (Pr) virus would induce the secretion of immunoglobulin A (IgA) antibodies in their milk as was observed after enteric infection with transmissible gastroenteritis (TGE) virus. The immune response of sows to Pr virus inoculated intranasally and to TGE virus inoculated orally/intranasally or via a natural infection was studied. Emphasis was placed upon titers and Ig classes of Pr and TGE virus-neutralizing antibodies in colostrum and milk. All animals exposed to Pr virus (alone or in combination with TGE virus) developed Pr-neutralizing antibody titers in both serum and milk. Pr antibody titers were generally higher in colostrum than in serum, but the opposite was true in milk compared with serum, with milk titers declining markedly during lactation. In contrast, TGE antibody titers in milk from experimentally or naturally infected sows usually remained higher than the corresponding serum titers and persisted at relatively constant levels throughout lactation. Gel filtration studies of milk indicated that the antibody activity against Pr virus was associated almost entirely with IgG fractions, with small amounts of antibody detectable in IgM fractions in colostrum from two of nine sows. By comparison, TGE antibodies were primarily of the IgA class, with varying but lesser amounts of antibody associated with the IgG class. Such results suggest that viral infection of the intestinal tract of the sow, but not the upper respiratory tract, stimulates the secretion of IgA antibodies in the milk.", "contents": "Immunoglobulin classes of antibodies in milk of swine after intranasal exposure to pseudorabies virus or transmissible gastroenteritis virus. Experiments were conducted to evaluate whether infection of the respiratory tract of pregnant swine with pseudorabies (Pr) virus would induce the secretion of immunoglobulin A (IgA) antibodies in their milk as was observed after enteric infection with transmissible gastroenteritis (TGE) virus. The immune response of sows to Pr virus inoculated intranasally and to TGE virus inoculated orally/intranasally or via a natural infection was studied. Emphasis was placed upon titers and Ig classes of Pr and TGE virus-neutralizing antibodies in colostrum and milk. All animals exposed to Pr virus (alone or in combination with TGE virus) developed Pr-neutralizing antibody titers in both serum and milk. Pr antibody titers were generally higher in colostrum than in serum, but the opposite was true in milk compared with serum, with milk titers declining markedly during lactation. In contrast, TGE antibody titers in milk from experimentally or naturally infected sows usually remained higher than the corresponding serum titers and persisted at relatively constant levels throughout lactation. Gel filtration studies of milk indicated that the antibody activity against Pr virus was associated almost entirely with IgG fractions, with small amounts of antibody detectable in IgM fractions in colostrum from two of nine sows. By comparison, TGE antibodies were primarily of the IgA class, with varying but lesser amounts of antibody associated with the IgG class. Such results suggest that viral infection of the intestinal tract of the sow, but not the upper respiratory tract, stimulates the secretion of IgA antibodies in the milk."}
{"id": "PMID:197015", "title": "Genetics of macrophage-controlled resistance to hepatitis induced by herpes simplex virus type 2 in mice.", "content": "The genetics of innate resistance of mice to hepatitis induced by herpes simplex virus type 2 (HSV-2) was analyzed by crossing resistant male GR to susceptible female BALB/c mice and backcrossing females of this F1 generation to susceptible male BALB/c mice. By scoring of macroscopic liver lesions and virus isolation studies from the liver 4 days after intraperitoneal inoculation of HSV-2, it appeared that the resistance was governed by one X-linked dominant gene or closely linked gene complex, as F1 female mice were resistant and F1 male mice were susceptible and the trait segregated in a ratio close to 1:1 in the backcross mating. A cellular expression in vitro of virus resistance was found in the macrophage population of the mice as measured by differences in the restriction of HSV-2 replication in macrophage cultures prepared from individual mice. In contrast to what was seen in macrophage cultures, virus replicated equally well in embryonic fibroblast cultures from susceptible and resistant strains of mice.", "contents": "Genetics of macrophage-controlled resistance to hepatitis induced by herpes simplex virus type 2 in mice. The genetics of innate resistance of mice to hepatitis induced by herpes simplex virus type 2 (HSV-2) was analyzed by crossing resistant male GR to susceptible female BALB/c mice and backcrossing females of this F1 generation to susceptible male BALB/c mice. By scoring of macroscopic liver lesions and virus isolation studies from the liver 4 days after intraperitoneal inoculation of HSV-2, it appeared that the resistance was governed by one X-linked dominant gene or closely linked gene complex, as F1 female mice were resistant and F1 male mice were susceptible and the trait segregated in a ratio close to 1:1 in the backcross mating. A cellular expression in vitro of virus resistance was found in the macrophage population of the mice as measured by differences in the restriction of HSV-2 replication in macrophage cultures prepared from individual mice. In contrast to what was seen in macrophage cultures, virus replicated equally well in embryonic fibroblast cultures from susceptible and resistant strains of mice."}
{"id": "PMID:197016", "title": "Effect of silica on the pathogenic distinction between herpes simplex virus type 1 and 2 hepatitis in mice.", "content": "The role of macrophages in the difference in liver pathogenicity between herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in mice was investigated by selectively blocking the macrophage function of the mice by silica. Intravenous administration of 3 mg of silica 2 h before virus inoculation partially abolished the difference between the two virus types, as judged by macroscopic and microscopic examination of the livers and by virus isolation studies. Intraperitoneal inoculation of 50 mg of silical before virus seemed more effective in suppressing the macrophage function, since this treatment almost completely eliminated the difference in hepatotropism between HSV-1 and HSV-2 as assessed by the number and size of the lesions appearing in the liver. The final outcome of the infection, death from encephalitis, was, however, not influenced by macrophage blockade.", "contents": "Effect of silica on the pathogenic distinction between herpes simplex virus type 1 and 2 hepatitis in mice. The role of macrophages in the difference in liver pathogenicity between herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in mice was investigated by selectively blocking the macrophage function of the mice by silica. Intravenous administration of 3 mg of silica 2 h before virus inoculation partially abolished the difference between the two virus types, as judged by macroscopic and microscopic examination of the livers and by virus isolation studies. Intraperitoneal inoculation of 50 mg of silical before virus seemed more effective in suppressing the macrophage function, since this treatment almost completely eliminated the difference in hepatotropism between HSV-1 and HSV-2 as assessed by the number and size of the lesions appearing in the liver. The final outcome of the infection, death from encephalitis, was, however, not influenced by macrophage blockade."}
{"id": "PMID:197017", "title": "Production by mixed lymphocyte cultures of a type II interferon able to protect macrophages against virus infection.", "content": "In supernatants of mixed mouse spleen cell cultures established for 4 days, a species-specific inhibitor of virus replication with a broad antiviral spectrum was found. The inhibitor was destroyed by trypsin, was nondialyzable and acid labile, and was not neutralized by antibody to mouse L cell interferon. This indicates that in mixed lymphocyte cultures a type II interferon is made that has no immunological relationship with \"fibroblast\" interferon. This leukocyte product was shown to protect mouse hepatitis viruses. It is suggested that lymphocyte interferon may collaborate with macrophages in host defense against viruses, as a mediator of cellular immunity.", "contents": "Production by mixed lymphocyte cultures of a type II interferon able to protect macrophages against virus infection. In supernatants of mixed mouse spleen cell cultures established for 4 days, a species-specific inhibitor of virus replication with a broad antiviral spectrum was found. The inhibitor was destroyed by trypsin, was nondialyzable and acid labile, and was not neutralized by antibody to mouse L cell interferon. This indicates that in mixed lymphocyte cultures a type II interferon is made that has no immunological relationship with \"fibroblast\" interferon. This leukocyte product was shown to protect mouse hepatitis viruses. It is suggested that lymphocyte interferon may collaborate with macrophages in host defense against viruses, as a mediator of cellular immunity."}
{"id": "PMID:197018", "title": "Commitment to deoxyribonulceic acid synthesis and the cell cycle in endotoxin-stimulated murine spleen cells.", "content": "Events associated with endotoxin-induced mitogenesis in murine spleen cells were investigated. Commitment to deoxyribonucleic acid (DNA) synthesis, the onset of DNA synthesis, and phases of cell cycle were timed. Increased levels of DNA synthesis in murine spleen cells stimulated with endotoxin were observed 12 to 16 h after the addition of the mitogen. The total cell cycle time of stimulated B-cells was 11 to 14 h. The S-phase was 8 h. The G2-phase was 1 h, and the combined M-plus G1-phase of cycling cells was 2 to 5 h. A 1- to 4-h exposure to lipopolysaccharide elicited a significant increase in DNA synthesis. Progressively longer exposures to lipopolysaccharide, up to 24 h, produced further increases in first-cycle DNA synthesis. Polymyxin B, when added with endotoxin to cultures from the outset, inhibited first-cycle DNA synthesis. However, if addition of the antibiotic was delayed, progressive increases in first-cycle dna synthesis were observed. These data indicate a heterogeneity among B-cells in their responsiveness to endotoxin.", "contents": "Commitment to deoxyribonulceic acid synthesis and the cell cycle in endotoxin-stimulated murine spleen cells. Events associated with endotoxin-induced mitogenesis in murine spleen cells were investigated. Commitment to deoxyribonucleic acid (DNA) synthesis, the onset of DNA synthesis, and phases of cell cycle were timed. Increased levels of DNA synthesis in murine spleen cells stimulated with endotoxin were observed 12 to 16 h after the addition of the mitogen. The total cell cycle time of stimulated B-cells was 11 to 14 h. The S-phase was 8 h. The G2-phase was 1 h, and the combined M-plus G1-phase of cycling cells was 2 to 5 h. A 1- to 4-h exposure to lipopolysaccharide elicited a significant increase in DNA synthesis. Progressively longer exposures to lipopolysaccharide, up to 24 h, produced further increases in first-cycle DNA synthesis. Polymyxin B, when added with endotoxin to cultures from the outset, inhibited first-cycle DNA synthesis. However, if addition of the antibiotic was delayed, progressive increases in first-cycle dna synthesis were observed. These data indicate a heterogeneity among B-cells in their responsiveness to endotoxin."}
{"id": "PMID:197019", "title": "In vitro studies on the mechanism of herpesvirus plaque growth inhibition by sensitized lymphocytes.", "content": "Inhibition of herpesvirus plaque growth was observed when herpes simplex virus (HSV)-sensitized rabbit lymphocytes were placed in contact with an HSV-infected human foreskin monolayer. This inhibition was obtained as early as 3 h when a ratio of 6 viable lymphocytes to target cells was used, and the supernatants of these cultures also demonstrated plaque size reduction when put onto newly infected cell monolayers. Interferon, which is present in this system, had no effect on HSV when tested on human foreskin monolayers, indicating that interferon was not the mechanism for plaque size reduction. Plaque growth inhibition was attributed to the T lymphocyte, because purified T cells reduced plaque growth and anti-rabbit thymocyte serum eliminated the effect of T cells. The specificity of this assay was determined by the facts that nonsensitized lymphocytes did not reduce the size of a plaque and the recognition of an infected cell by the sensitized lymphocyte was necessary for the release of a soluble mediator into the supernatant fluid. This cytotoxic lymphocyte was detected in the peripheral blood of rabbits as early as 4 days after initial corneal infection, with a maximum response at 7 to 10 days.", "contents": "In vitro studies on the mechanism of herpesvirus plaque growth inhibition by sensitized lymphocytes. Inhibition of herpesvirus plaque growth was observed when herpes simplex virus (HSV)-sensitized rabbit lymphocytes were placed in contact with an HSV-infected human foreskin monolayer. This inhibition was obtained as early as 3 h when a ratio of 6 viable lymphocytes to target cells was used, and the supernatants of these cultures also demonstrated plaque size reduction when put onto newly infected cell monolayers. Interferon, which is present in this system, had no effect on HSV when tested on human foreskin monolayers, indicating that interferon was not the mechanism for plaque size reduction. Plaque growth inhibition was attributed to the T lymphocyte, because purified T cells reduced plaque growth and anti-rabbit thymocyte serum eliminated the effect of T cells. The specificity of this assay was determined by the facts that nonsensitized lymphocytes did not reduce the size of a plaque and the recognition of an infected cell by the sensitized lymphocyte was necessary for the release of a soluble mediator into the supernatant fluid. This cytotoxic lymphocyte was detected in the peripheral blood of rabbits as early as 4 days after initial corneal infection, with a maximum response at 7 to 10 days."}
{"id": "PMID:197020", "title": "Role of viremia in the suppression of T-cell function during murine cytomegalovirus infection.", "content": "The suppression of T-cell deoxyribonucleic acid (DNA) synthesis by serum from mice acutely with murine cytomegalovirus (MCMV) was investigated. Spleen cells from uninfected mice were exposed to concanavalin A in the presence of serum taken from mice at various times after infection with MCMV. The capacity of the serum to suppress DNA synthesis first appeared at day 3 postinfection and was associated with free infectious virus. Addition of MCMV to serum from uninfected mice also suppressed DNA synthesis. Ultracentrifugation of serum from mice acutely infected with MCMV removed most of the virus and aborgated the inhibition of DNA synthesis. However, in two of four experiments, serum from mice in weeks 4 and 5 postinfection did not contain infectious MCMB but did suppress. Therefore, it appears that MCMV itself can suppress DNA synthesis of T cells; however, this may not be the exclusive mechanism of suppression exerted by serum from MCMB-infected mice.", "contents": "Role of viremia in the suppression of T-cell function during murine cytomegalovirus infection. The suppression of T-cell deoxyribonucleic acid (DNA) synthesis by serum from mice acutely with murine cytomegalovirus (MCMV) was investigated. Spleen cells from uninfected mice were exposed to concanavalin A in the presence of serum taken from mice at various times after infection with MCMV. The capacity of the serum to suppress DNA synthesis first appeared at day 3 postinfection and was associated with free infectious virus. Addition of MCMV to serum from uninfected mice also suppressed DNA synthesis. Ultracentrifugation of serum from mice acutely infected with MCMV removed most of the virus and aborgated the inhibition of DNA synthesis. However, in two of four experiments, serum from mice in weeks 4 and 5 postinfection did not contain infectious MCMB but did suppress. Therefore, it appears that MCMV itself can suppress DNA synthesis of T cells; however, this may not be the exclusive mechanism of suppression exerted by serum from MCMB-infected mice."}
{"id": "PMID:197021", "title": "Preparative polyacrylamide gel electrophoresis purification of Clostridium perfringens enterotoxin.", "content": "Preparative polyacrylamide gel electrophoresis has been used to purify the enterotoxin of Clostridium perfringens from Sephadex G-100 extracts. Purified toxin of high specific activity was eluted in 1 to 3 h, depending upon the length of the acrylamide gel used. Recovery of biological activity with this technique ranged from 80 to 90%. The purity and physical characteristics of the toxin were similar to those previously reported for the protein purified by other methods. Use of preparative electrophoresis will enable the production of larger amounts of high-specific-activity toxin in a shorter time than other currently available procedures. This method was also used to isolate a form of enterotoxin that has a mobility, relative to bromophenol blue tracking dye, of 0.87 to 0.90 in 7% acrylamide gels.", "contents": "Preparative polyacrylamide gel electrophoresis purification of Clostridium perfringens enterotoxin. Preparative polyacrylamide gel electrophoresis has been used to purify the enterotoxin of Clostridium perfringens from Sephadex G-100 extracts. Purified toxin of high specific activity was eluted in 1 to 3 h, depending upon the length of the acrylamide gel used. Recovery of biological activity with this technique ranged from 80 to 90%. The purity and physical characteristics of the toxin were similar to those previously reported for the protein purified by other methods. Use of preparative electrophoresis will enable the production of larger amounts of high-specific-activity toxin in a shorter time than other currently available procedures. This method was also used to isolate a form of enterotoxin that has a mobility, relative to bromophenol blue tracking dye, of 0.87 to 0.90 in 7% acrylamide gels."}
{"id": "PMID:197022", "title": "Role of T lymphocytes in recovery from murine cytomegalovirus infection.", "content": "Congenitally athymic nude (Nu/Nu) mice inoculated intraperitoneally with murine cytomegalovirus (MCMV), in doses as low as 1.3 X 10(1) plaque-forming units succumbed to the infection. In contrast, the mean lethal dose for heteroxygous euthymic (Nu/+) littermates was 4 X 10(3) plaque-forming units. Though histopathological changes consistent with MCMV infection were found in the spleen, lungs, and adrenals of nude mice, there were only small focal areas of involvement in the liver. In contrast, Nu/+ mice dying from infection had pathological evidence of severe hepatitis. Spleen cells from immune and control BALB/c mice were injected intravenously into syngeneic mice that had been inoculated previously with lethal doses of MCMV intraperitoneally. Mice receiving 1 X 10(7) or more immune spleen cells were protected against the infection, whereas mice receiving 1 X 10(8) control spleen cells or immune serum were not. Treatment of immune spleen cells with anti-theta serum and complement significantly reduced their protective effect. Immune mechanisms associated with T lymphocytes appear to be critical for recovery from MCMV infection.", "contents": "Role of T lymphocytes in recovery from murine cytomegalovirus infection. Congenitally athymic nude (Nu/Nu) mice inoculated intraperitoneally with murine cytomegalovirus (MCMV), in doses as low as 1.3 X 10(1) plaque-forming units succumbed to the infection. In contrast, the mean lethal dose for heteroxygous euthymic (Nu/+) littermates was 4 X 10(3) plaque-forming units. Though histopathological changes consistent with MCMV infection were found in the spleen, lungs, and adrenals of nude mice, there were only small focal areas of involvement in the liver. In contrast, Nu/+ mice dying from infection had pathological evidence of severe hepatitis. Spleen cells from immune and control BALB/c mice were injected intravenously into syngeneic mice that had been inoculated previously with lethal doses of MCMV intraperitoneally. Mice receiving 1 X 10(7) or more immune spleen cells were protected against the infection, whereas mice receiving 1 X 10(8) control spleen cells or immune serum were not. Treatment of immune spleen cells with anti-theta serum and complement significantly reduced their protective effect. Immune mechanisms associated with T lymphocytes appear to be critical for recovery from MCMV infection."}
{"id": "PMID:197024", "title": "Human lymphoblastoid cell lines derived from individuals without lymphoproliferative disease contain the same latent forms of Epstein-Barr virus DNA as those found in tumor cells.", "content": "The physical state of the intracellular Epstein-Barr virus DNA was characterized in four human lymphoblastoid cell lines, F-265, NC-37, U-303 L, and PG-1, derived from individuals without lymphoproliferative disease. For comparison, a previously investigated Burkitt lymphoma line, Raji, and a more recently established cell line of that origin, Rael, were also studied. The techniques employed were CsCl density gradient centrifugation, glycerol gradient centrifugation, and ethidium bromide-CsCl density gradient centrifugation in combination with nucleic acid hybridization, as well as electron microscopy contour length measurements of purified circular EBV DNA. All six cell lines contained multiple copies of covalently closed circular EBV DNA-molecules of the same size, as well as viral DNA with the properties of integrated DNA. No differences could be detected between the forms of EBV DNA present in cell lines derived from non-malignant sources and those present in lymphoma lines.", "contents": "Human lymphoblastoid cell lines derived from individuals without lymphoproliferative disease contain the same latent forms of Epstein-Barr virus DNA as those found in tumor cells. The physical state of the intracellular Epstein-Barr virus DNA was characterized in four human lymphoblastoid cell lines, F-265, NC-37, U-303 L, and PG-1, derived from individuals without lymphoproliferative disease. For comparison, a previously investigated Burkitt lymphoma line, Raji, and a more recently established cell line of that origin, Rael, were also studied. The techniques employed were CsCl density gradient centrifugation, glycerol gradient centrifugation, and ethidium bromide-CsCl density gradient centrifugation in combination with nucleic acid hybridization, as well as electron microscopy contour length measurements of purified circular EBV DNA. All six cell lines contained multiple copies of covalently closed circular EBV DNA-molecules of the same size, as well as viral DNA with the properties of integrated DNA. No differences could be detected between the forms of EBV DNA present in cell lines derived from non-malignant sources and those present in lymphoma lines."}
{"id": "PMID:197025", "title": "Transformation of lymphocytes by Herpesvirus papio.", "content": "Cotton-topped (CT) or white-lipped (WL) marmoset lymphocytes were transformed in vitro with herpesvirus papio (HVP) into permanently growing lymphoblastoid cell lines (LCL). Five of 9 HVP-transformed CT cell lines contained cells with antigens reacting with antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and/or to EBV-induced early antigens (EA). None of 12 WL LCL revealed such antigen-producing cells. Cells from both groups of cultures failed to react with antibodies to the EBV-specified nuclear antigen (EBNA). Exposure of baboon circulating lymphocytes to X-irradiated HVP or EBV-carring cells, or to suspensions of EBV resulted in establishment of LCL which all contained VCA and/or EA-positive, but no EBNA-positive cells. Nuclear antigens were undetectable also with anti-VCA-positive sera from baboons, chimpanzees, or other non-human primates. DNA-complementary RNA (cRNA) filter hybridization with EBV cRNA showed that with one exception transformed CT or WL marmoset cells contained at least 1-2 virus genome equivalents per cell, while at least 12-25 virus genome equivalents per cell were detected in transformed baboon cells. These data need confirmation by DNA-DNA reassociation kinetics.", "contents": "Transformation of lymphocytes by Herpesvirus papio. Cotton-topped (CT) or white-lipped (WL) marmoset lymphocytes were transformed in vitro with herpesvirus papio (HVP) into permanently growing lymphoblastoid cell lines (LCL). Five of 9 HVP-transformed CT cell lines contained cells with antigens reacting with antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and/or to EBV-induced early antigens (EA). None of 12 WL LCL revealed such antigen-producing cells. Cells from both groups of cultures failed to react with antibodies to the EBV-specified nuclear antigen (EBNA). Exposure of baboon circulating lymphocytes to X-irradiated HVP or EBV-carring cells, or to suspensions of EBV resulted in establishment of LCL which all contained VCA and/or EA-positive, but no EBNA-positive cells. Nuclear antigens were undetectable also with anti-VCA-positive sera from baboons, chimpanzees, or other non-human primates. DNA-complementary RNA (cRNA) filter hybridization with EBV cRNA showed that with one exception transformed CT or WL marmoset cells contained at least 1-2 virus genome equivalents per cell, while at least 12-25 virus genome equivalents per cell were detected in transformed baboon cells. These data need confirmation by DNA-DNA reassociation kinetics."}
{"id": "PMID:197026", "title": "Productive Epstein-Barr viral infection of the human lymphoblastoid cell line 6410 with release of early antigen inducing and transforming virus.", "content": "The human lymphoblastoid cell line 6410 was superinfected with P3HR-1 derived Epstein-Barr virus. Subsequent to the first cycle of infection, characterized by early (EA) and virus capsid (VCA) antigen synthesis, the culture, designated 6410-EBV, continued to synthesize VCA. Further immunofluorescence and electron microscopic examination over 18-24 months showed the 6410-EBV culture to be productively infected with EBV. Virus was recovered, in quantity, from the culture fluids and assayed for ability to induce EA synthesis in Raji cells and to transform human umbilical cord lymphocytes. The virus was found to possess both properties, in contrast to P3HR-1 virus which only induces EA. HLA and karyologic analyses of P3HR-1, 6410 and 6410-EBV cultures showed relatedness of 6410-EBV to 6410 cells and dissimilarity to P3HR-1. The biologic activity data coupled with the cytologic analyses confirm a productive infection of the target cells. The reason for differences in biologic activity between the infecting (P3HR-1) and progeny virus is unresolved. It may be speculated that the endogenous EBV genome of 6410 cells was activated and gave rise to a different strain of EBV or to a mixed progeny-parent population as a result of dual infection. Alternatively, the parent strain of virus may have been modfied as a result of interaction with the new host cell.", "contents": "Productive Epstein-Barr viral infection of the human lymphoblastoid cell line 6410 with release of early antigen inducing and transforming virus. The human lymphoblastoid cell line 6410 was superinfected with P3HR-1 derived Epstein-Barr virus. Subsequent to the first cycle of infection, characterized by early (EA) and virus capsid (VCA) antigen synthesis, the culture, designated 6410-EBV, continued to synthesize VCA. Further immunofluorescence and electron microscopic examination over 18-24 months showed the 6410-EBV culture to be productively infected with EBV. Virus was recovered, in quantity, from the culture fluids and assayed for ability to induce EA synthesis in Raji cells and to transform human umbilical cord lymphocytes. The virus was found to possess both properties, in contrast to P3HR-1 virus which only induces EA. HLA and karyologic analyses of P3HR-1, 6410 and 6410-EBV cultures showed relatedness of 6410-EBV to 6410 cells and dissimilarity to P3HR-1. The biologic activity data coupled with the cytologic analyses confirm a productive infection of the target cells. The reason for differences in biologic activity between the infecting (P3HR-1) and progeny virus is unresolved. It may be speculated that the endogenous EBV genome of 6410 cells was activated and gave rise to a different strain of EBV or to a mixed progeny-parent population as a result of dual infection. Alternatively, the parent strain of virus may have been modfied as a result of interaction with the new host cell."}
{"id": "PMID:197028", "title": "Tumour-specific complement-dependent serum cytotoxicity against a chemically induced rat hepatoma.", "content": "A short-term 51Cr release test was used for the detection of complement-dependent cytolytic activity of syngeneic serum for transplanted aminoazo dye-induced rat hepatoma cells in suspension. Serum samples from rats bearing intraperitoneal implants of one hepatoma (hepatoma D23) were specifically cytotoxic for hepatoma D23 target cells, although this activity was not detected in sera from donors bearing subcutaneous tumour grafts. Other sera containing demonstrable IgG antibodies reactive in membrane immunofluorescence tests with individually distinct tumour-specific antigens or tumour-associated embryonic antigens were not cytotoxic for hepatoma D23 cells; and even though serum from donors carrying intraperitoneal tumour grafts contained tumour-specific IgG antibody, the complement-dependent reactivity was confined to the 19s region of fractionated tumour-bearer serum. These findings are discussed in relation to the development of humoral responses in the tumour-bearing host and with regard to the significance of the availability of an objective and reproducible assay for measuring humoral responses directed against the tumour-specific antigens associated with chemically induced rat tumours.", "contents": "Tumour-specific complement-dependent serum cytotoxicity against a chemically induced rat hepatoma. A short-term 51Cr release test was used for the detection of complement-dependent cytolytic activity of syngeneic serum for transplanted aminoazo dye-induced rat hepatoma cells in suspension. Serum samples from rats bearing intraperitoneal implants of one hepatoma (hepatoma D23) were specifically cytotoxic for hepatoma D23 target cells, although this activity was not detected in sera from donors bearing subcutaneous tumour grafts. Other sera containing demonstrable IgG antibodies reactive in membrane immunofluorescence tests with individually distinct tumour-specific antigens or tumour-associated embryonic antigens were not cytotoxic for hepatoma D23 cells; and even though serum from donors carrying intraperitoneal tumour grafts contained tumour-specific IgG antibody, the complement-dependent reactivity was confined to the 19s region of fractionated tumour-bearer serum. These findings are discussed in relation to the development of humoral responses in the tumour-bearing host and with regard to the significance of the availability of an objective and reproducible assay for measuring humoral responses directed against the tumour-specific antigens associated with chemically induced rat tumours."}
{"id": "PMID:197029", "title": "Possible two-stage transplacental liver carcinogenesis in C57BL/6 mice.", "content": "A single SC injection of 2-acetylaminofluorene (AAF) was given to pregnant C57BL/6 mice on day 15 of gestation, and the offspring subsequently given twice-weekly injections of phorbol for 25 weeks. Control groups included: (1) untreated; (2) AAF-treated mothers (kept under observation for 18 months, as with all the other groups); (3) untreated offspring of untreated mothers; (4) untreated offspring of AAF-treated mothers, and (5) phorbol-treated offspring of untreated mothers. The incidence of hepatomas in the phorbol-treated offspring of AAF-injected mothers was 8/74 (11%), as compared with 2/80 (2.5%) in the untreated offspring of AAF-injected mothers. The AAF-injected mothers themselves developed 3/36 (8%) hepatomas; while all othe other control groups were free from liver tumours. The development of reticulum cell sarcomas, and of a few cases of lung adenomas, in the various groups, was presumably spontaneous. The results seem sufficiently encouraging, as a model for the study of systemic carcinogenesis, to warrant further attempts at two-stage transplacental carcinogenesis, using other potential initiators and promoters.", "contents": "Possible two-stage transplacental liver carcinogenesis in C57BL/6 mice. A single SC injection of 2-acetylaminofluorene (AAF) was given to pregnant C57BL/6 mice on day 15 of gestation, and the offspring subsequently given twice-weekly injections of phorbol for 25 weeks. Control groups included: (1) untreated; (2) AAF-treated mothers (kept under observation for 18 months, as with all the other groups); (3) untreated offspring of untreated mothers; (4) untreated offspring of AAF-treated mothers, and (5) phorbol-treated offspring of untreated mothers. The incidence of hepatomas in the phorbol-treated offspring of AAF-injected mothers was 8/74 (11%), as compared with 2/80 (2.5%) in the untreated offspring of AAF-injected mothers. The AAF-injected mothers themselves developed 3/36 (8%) hepatomas; while all othe other control groups were free from liver tumours. The development of reticulum cell sarcomas, and of a few cases of lung adenomas, in the various groups, was presumably spontaneous. The results seem sufficiently encouraging, as a model for the study of systemic carcinogenesis, to warrant further attempts at two-stage transplacental carcinogenesis, using other potential initiators and promoters."}
{"id": "PMID:197032", "title": "Strategy of goitre and cretinism control in Central Africa.", "content": "Goitre prevalence in Ubangi Mongala (north-western Za\u00efre) ranges from 27 to 60 per cent in the male population and from 48 to 78 per cent in the female population; the prevalence of cretinism ranges between 0.7 and 7.6 per cent. This severe endemia affects 1.5 million inhabitants and constitutes a major public health problem. If administered to an entire population, single injections of slowly resorbable iodized oil can reduce goitre prevalence substantially, correct the iodine deficiency and restore normal thyroid function for a period of 3 to 7 years, depending on the parameter considered. The cost of programme of endemic goitre prevention based on this method can be estimated at 0.07 US dollars per person and per year of protection. A strategy of goitre and cretinism control in Central Africa, using iodized oil in an attack phase and iodized salt in a follow-up phase, is proposed. The organization of this programme will be dovetailed into other public health activities and will strengthen the basic health service framework.", "contents": "Strategy of goitre and cretinism control in Central Africa. Goitre prevalence in Ubangi Mongala (north-western Za\u00efre) ranges from 27 to 60 per cent in the male population and from 48 to 78 per cent in the female population; the prevalence of cretinism ranges between 0.7 and 7.6 per cent. This severe endemia affects 1.5 million inhabitants and constitutes a major public health problem. If administered to an entire population, single injections of slowly resorbable iodized oil can reduce goitre prevalence substantially, correct the iodine deficiency and restore normal thyroid function for a period of 3 to 7 years, depending on the parameter considered. The cost of programme of endemic goitre prevention based on this method can be estimated at 0.07 US dollars per person and per year of protection. A strategy of goitre and cretinism control in Central Africa, using iodized oil in an attack phase and iodized salt in a follow-up phase, is proposed. The organization of this programme will be dovetailed into other public health activities and will strengthen the basic health service framework."}
{"id": "PMID:197033", "title": "Comparison of poliovirus detection in sewage and stool samples; a study in a cr\u00e8che in the third week after vaccination.", "content": "In a model experiment conducted in a Prague cr\u00e8che, the detection rate for polioviruses in partially purified, non-concentrated sewage as sampled by means of gauze pads (Moore's method) was compared with that for individual stool samples. In the third week after the vaccination of children with live attenuated type 1 poliovirus (March 1975) and at an equal interval after their vaccination with a combination of types 2 and 3 (May 1975), corresponding poliovirus types were detected both in individual stool samples and sewage. The mean amount of sewage virus recovered during one week was directly proportional to the percentage of positive stool samples. After combined type 2 and 3 poliovirus administration, however, both types were only detected in one sewage sample, while in two samples type 3 only, and in one sample type 2 only, were identified. The results of the study indicate that poliovirus is detectable in sewage by the method employed if it is excreted by approximately one per cent of persons in the sewer catchment area of a small community. If a number of antigenic types are simultaneously present, their identification requires systematic examination of the sewage.", "contents": "Comparison of poliovirus detection in sewage and stool samples; a study in a cr\u00e8che in the third week after vaccination. In a model experiment conducted in a Prague cr\u00e8che, the detection rate for polioviruses in partially purified, non-concentrated sewage as sampled by means of gauze pads (Moore's method) was compared with that for individual stool samples. In the third week after the vaccination of children with live attenuated type 1 poliovirus (March 1975) and at an equal interval after their vaccination with a combination of types 2 and 3 (May 1975), corresponding poliovirus types were detected both in individual stool samples and sewage. The mean amount of sewage virus recovered during one week was directly proportional to the percentage of positive stool samples. After combined type 2 and 3 poliovirus administration, however, both types were only detected in one sewage sample, while in two samples type 3 only, and in one sample type 2 only, were identified. The results of the study indicate that poliovirus is detectable in sewage by the method employed if it is excreted by approximately one per cent of persons in the sewer catchment area of a small community. If a number of antigenic types are simultaneously present, their identification requires systematic examination of the sewage."}
{"id": "PMID:197034", "title": "Studies on cytochrome C. XII. Synthesis of the protected undecapeptide (sequence 66-76) and pentadecapeptide (sequence 66-80) of horse heart cytochrome c.", "content": "This paper is part of a series on synthesis of suitably protected peptides covering the 66-104 sequence of horse heart cytochrome c. It describes the preparation, by conventional procedures, of a partially protected N alpha-benzyloxycarbonyl-undecapeptide hydrazide corresponding to the sequence from 66 to 76 (Fragment F), which represents a building block for the synthesis of the entire 66-104 sequence. Moreover, the preparation is described of a partially protected pentadecapeptide corresponding to the sequence region 66 to 80, which represents the key peptide for the semisynthesis of the same COOH-terminal sequence utilizing the natural 81-104 N epsilon-trifluoroacetylated CNBr fragment.", "contents": "Studies on cytochrome C. XII. Synthesis of the protected undecapeptide (sequence 66-76) and pentadecapeptide (sequence 66-80) of horse heart cytochrome c. This paper is part of a series on synthesis of suitably protected peptides covering the 66-104 sequence of horse heart cytochrome c. It describes the preparation, by conventional procedures, of a partially protected N alpha-benzyloxycarbonyl-undecapeptide hydrazide corresponding to the sequence from 66 to 76 (Fragment F), which represents a building block for the synthesis of the entire 66-104 sequence. Moreover, the preparation is described of a partially protected pentadecapeptide corresponding to the sequence region 66 to 80, which represents the key peptide for the semisynthesis of the same COOH-terminal sequence utilizing the natural 81-104 N epsilon-trifluoroacetylated CNBr fragment."}
{"id": "PMID:197035", "title": "Studies on cytochrome C. XIII. Synthesis of the protected undecapeptide (sequence 77-87) of horse heart cytochrome c.", "content": "A solution synthesis of Z-Gly-Thr-Lys (Tfa)-Met-Ile-Phe-Ala-Gly-Ile-Lys (Tfa)-Lys (Tfa)-NHNH-Boc corresponding to the sequence 77-87 of horse heart cytochrome c is described. The protected undecapeptide was obtained from intermediate hepta- and tetrapeptide fragments by an azide coupling.", "contents": "Studies on cytochrome C. XIII. Synthesis of the protected undecapeptide (sequence 77-87) of horse heart cytochrome c. A solution synthesis of Z-Gly-Thr-Lys (Tfa)-Met-Ile-Phe-Ala-Gly-Ile-Lys (Tfa)-Lys (Tfa)-NHNH-Boc corresponding to the sequence 77-87 of horse heart cytochrome c is described. The protected undecapeptide was obtained from intermediate hepta- and tetrapeptide fragments by an azide coupling."}
{"id": "PMID:197036", "title": "Studies on cytochrome c. XIV. Synthesis of the protected heptadecapeptide (sequence 88-104) of horse heart cytochrome c.", "content": "A solution synthesis is described of the partially protected N alpha-benzyloxycarbonylheptadecapeptide Z-Lys (Tfa)-Thr-Glu-Arg-Glu-Asp-Leu-Ile-Ala-Tyr-Leu-Lys (Tfa)-Lys (Tfa)-Ala-Thr-Asn-Glu (OBu t)-OBu t corresponding to sequence 88-104 of horse heart cytochrome c. The synthesis is achieved through the preparation of two subunits H1 (sequence 88-96) and H2 (sequence 97-104) and their linkage by an azide coupling step.", "contents": "Studies on cytochrome c. XIV. Synthesis of the protected heptadecapeptide (sequence 88-104) of horse heart cytochrome c. A solution synthesis is described of the partially protected N alpha-benzyloxycarbonylheptadecapeptide Z-Lys (Tfa)-Thr-Glu-Arg-Glu-Asp-Leu-Ile-Ala-Tyr-Leu-Lys (Tfa)-Lys (Tfa)-Ala-Thr-Asn-Glu (OBu t)-OBu t corresponding to sequence 88-104 of horse heart cytochrome c. The synthesis is achieved through the preparation of two subunits H1 (sequence 88-96) and H2 (sequence 97-104) and their linkage by an azide coupling step."}
{"id": "PMID:197037", "title": "Characteristics of dimer formation, excision and DNA strand growth in Yoshida sensitive and resistant cells after ultraviolet irradiation.", "content": "The sedimentation properties of the nascent DNA of Yoshida sarcoma cells, sensitive and resistant to methylene dimethane sulphonate and cross-resistant to U.V. light, have been studied after irradiation with U.V. light at 11 and 22J/m2. It has been shown that the DNA formed immediately after irradiation with 11J/m2 is some eight to nine times longer than the calculated inter--dimer distance in both cell-lines. Differences were, however, observed between the two cell-lines, in that the absence of excision of dimers in the sensitive cells was accompanied by the formation of a DNA component of low molecular weight, whereas excision in the resistant line was not so accompanied. There are some similarities between the Yoshida tumour line sensitive to methylene dimethane sulphonate and the U.V.-sensitive line of Xeroderma pigmentosum.", "contents": "Characteristics of dimer formation, excision and DNA strand growth in Yoshida sensitive and resistant cells after ultraviolet irradiation. The sedimentation properties of the nascent DNA of Yoshida sarcoma cells, sensitive and resistant to methylene dimethane sulphonate and cross-resistant to U.V. light, have been studied after irradiation with U.V. light at 11 and 22J/m2. It has been shown that the DNA formed immediately after irradiation with 11J/m2 is some eight to nine times longer than the calculated inter--dimer distance in both cell-lines. Differences were, however, observed between the two cell-lines, in that the absence of excision of dimers in the sensitive cells was accompanied by the formation of a DNA component of low molecular weight, whereas excision in the resistant line was not so accompanied. There are some similarities between the Yoshida tumour line sensitive to methylene dimethane sulphonate and the U.V.-sensitive line of Xeroderma pigmentosum."}
{"id": "PMID:197043", "title": "Immunoelectron microscopic localization of herpes simplex virus antigens in rabbit cornea with antihuman IgG-antiferritin hybrid antibodies.", "content": "Sheep antihuman IgG-antiferritin hybrid antibodies were used for the ultrastructural localization of herpes simplex virus (HSV) antigens in rabbit corneas from animals with herpetic keratitis. In animals with epithelial keratitis in which active viral replication is occurring (6 days after infection), viral antigen was found within nuclei, on nuclear membranes, and on cell surface membranes of epithelial cells. In animals with early necrotizing keratitis in which active viral replication cannot be demonstrated (14 to 21 days after infection), viral antigen was found in association with the cell surface of stromal keratocytes. Since lymphocytic cells in intimate contact with degenerating keratocytes have previously been identified in the cornea, these observations provide a basis for the view that cell-mediated immunopathogenesis is involved in the etiology of herpetic stromal keratitis.", "contents": "Immunoelectron microscopic localization of herpes simplex virus antigens in rabbit cornea with antihuman IgG-antiferritin hybrid antibodies. Sheep antihuman IgG-antiferritin hybrid antibodies were used for the ultrastructural localization of herpes simplex virus (HSV) antigens in rabbit corneas from animals with herpetic keratitis. In animals with epithelial keratitis in which active viral replication is occurring (6 days after infection), viral antigen was found within nuclei, on nuclear membranes, and on cell surface membranes of epithelial cells. In animals with early necrotizing keratitis in which active viral replication cannot be demonstrated (14 to 21 days after infection), viral antigen was found in association with the cell surface of stromal keratocytes. Since lymphocytic cells in intimate contact with degenerating keratocytes have previously been identified in the cornea, these observations provide a basis for the view that cell-mediated immunopathogenesis is involved in the etiology of herpetic stromal keratitis."}
{"id": "PMID:197044", "title": "Lysozyme tear level in patients with herpes simplex virus eye infection.", "content": "The lysozyme level in tears of patients with HSV eye infection was examined and correlated with the clinical findings and presence of virus. The concentration of the enzyme in tears of patients during acute attack was 2.83 mg./ml. This value was significantly lower than that in tears from healthy controls (6.1 mg./ml.) and tears from the patient's healthy eye (4.46 mg./ml.). After termination of treatment with either IUDR or poly I:C, the lysozyme level rose to an average of 4.34 mg./ml. During the latent period of the disease the level increased (5.34 mg./ml.), but it remained lower than in healthy subjects who had never suffered from HSV eye infection. This may be an indicator of possible future recurrences.", "contents": "Lysozyme tear level in patients with herpes simplex virus eye infection. The lysozyme level in tears of patients with HSV eye infection was examined and correlated with the clinical findings and presence of virus. The concentration of the enzyme in tears of patients during acute attack was 2.83 mg./ml. This value was significantly lower than that in tears from healthy controls (6.1 mg./ml.) and tears from the patient's healthy eye (4.46 mg./ml.). After termination of treatment with either IUDR or poly I:C, the lysozyme level rose to an average of 4.34 mg./ml. During the latent period of the disease the level increased (5.34 mg./ml.), but it remained lower than in healthy subjects who had never suffered from HSV eye infection. This may be an indicator of possible future recurrences."}
{"id": "PMID:197045", "title": "Characterization of purely ecotropic and amphotropic naturally occurring wild mouse leukemia viruses.", "content": "Two new strains of murine leukemia virus, one (strain 4996) purely ecotropic and the other (strain 1313) purely amphotropic, were isolated from spontaneous lymphomas in aged wild mice (Mus musculus). The 4996 virus is the first wild mouse field isolate which consists solely of ecotropic virus without the concomitant presence of amphotropic virus. The 1313 isolate is distinct in host range from seven other previously described wild mouse amphotropic isolates and is also the only murine leukemia virus shown to replicate in chicken cells.", "contents": "Characterization of purely ecotropic and amphotropic naturally occurring wild mouse leukemia viruses. Two new strains of murine leukemia virus, one (strain 4996) purely ecotropic and the other (strain 1313) purely amphotropic, were isolated from spontaneous lymphomas in aged wild mice (Mus musculus). The 4996 virus is the first wild mouse field isolate which consists solely of ecotropic virus without the concomitant presence of amphotropic virus. The 1313 isolate is distinct in host range from seven other previously described wild mouse amphotropic isolates and is also the only murine leukemia virus shown to replicate in chicken cells."}
{"id": "PMID:197046", "title": "Identification and characterization of a papillomavirus from birds (Fringillidae).", "content": "From skin papillomas of the chaffinch (Fringilla coelebs), a virus has been purified and studied by physicochemical techniques and electron microscopy. The virions measure 52 nm in diameter and are composed of 72 morphological units arranged in a skew T = 7d surface lattice. A sedimentation coefficient of about 300S and a buoyant density of 1.34 g/ml in CsCl were determined for the particle. Its protein composition resembles that of human papillomavirus, and the circular double-stranded genome measures 2.6 micronm. This is the first demonstration of a member of the Papovaviridae family that affects a nonmammalian host.", "contents": "Identification and characterization of a papillomavirus from birds (Fringillidae). From skin papillomas of the chaffinch (Fringilla coelebs), a virus has been purified and studied by physicochemical techniques and electron microscopy. The virions measure 52 nm in diameter and are composed of 72 morphological units arranged in a skew T = 7d surface lattice. A sedimentation coefficient of about 300S and a buoyant density of 1.34 g/ml in CsCl were determined for the particle. Its protein composition resembles that of human papillomavirus, and the circular double-stranded genome measures 2.6 micronm. This is the first demonstration of a member of the Papovaviridae family that affects a nonmammalian host."}
{"id": "PMID:197047", "title": "A rapid method for detecting Junin virus viremia in the guinea pig.", "content": "A method for detecting Junin virus viremia in guinea pigs is described. The method consists of infecting BHK-21 cells with blood samples from infected guinea pigs; 48 h later, Junin virus antigens are detected in the cells by indirect immunofluorescence. Application of this technique to patients with Argentine hemorrhagic fever may lead to the quickest method for the virologic diagnosis of this disease.", "contents": "A rapid method for detecting Junin virus viremia in the guinea pig. A method for detecting Junin virus viremia in guinea pigs is described. The method consists of infecting BHK-21 cells with blood samples from infected guinea pigs; 48 h later, Junin virus antigens are detected in the cells by indirect immunofluorescence. Application of this technique to patients with Argentine hemorrhagic fever may lead to the quickest method for the virologic diagnosis of this disease."}
{"id": "PMID:197050", "title": "Application of enzymehistochemical methods to isolated subcellular fractions and to sucrose-ficoll density gradients. A contribution to the comparison of histochemical and biochemical data.", "content": "To compare histochemical and biochemical determinations of enzyme activities, enzymehistochemical procedures are applied to sections of pellets of subcelluar fractions. These investigations are of value to determine the subcellular localization of histochemically demonstrable enzyme activities and to test the homogeneity of an isolated fraction. In homogenating duckling liver a great part of the endothelial cells is not destructed and consequently is found in the nuclear fraction. Kupffer cell lysosomes land in the heavy mitochondrial fraction, whereas hepatocyte lysosomes are chiefly found in the light mitochondrial fraction. beta-Glucuronidase activity shows a preferentially microsomal localization. Application of enzymehistochemical staining reactions to discontinuous gradients and comparison with biochemical data provides additional information about the validity of an enzymehistochemical reaction. In rat liver the tetrazolium reductases show a distinctly dual localization: activity in the mitochondrial band and in microsomal bands. As to their localization in different bands of the gradients non-specific esterases demonstrate a clear pH-dependency.", "contents": "Application of enzymehistochemical methods to isolated subcellular fractions and to sucrose-ficoll density gradients. A contribution to the comparison of histochemical and biochemical data. To compare histochemical and biochemical determinations of enzyme activities, enzymehistochemical procedures are applied to sections of pellets of subcelluar fractions. These investigations are of value to determine the subcellular localization of histochemically demonstrable enzyme activities and to test the homogeneity of an isolated fraction. In homogenating duckling liver a great part of the endothelial cells is not destructed and consequently is found in the nuclear fraction. Kupffer cell lysosomes land in the heavy mitochondrial fraction, whereas hepatocyte lysosomes are chiefly found in the light mitochondrial fraction. beta-Glucuronidase activity shows a preferentially microsomal localization. Application of enzymehistochemical staining reactions to discontinuous gradients and comparison with biochemical data provides additional information about the validity of an enzymehistochemical reaction. In rat liver the tetrazolium reductases show a distinctly dual localization: activity in the mitochondrial band and in microsomal bands. As to their localization in different bands of the gradients non-specific esterases demonstrate a clear pH-dependency."}
{"id": "PMID:197055", "title": "Gas-liquid chromatographic determination of residues of methanesulfonate of n-aminobenzoic acid ethyl ester in fish.", "content": "In this gas-liquid chromatographic procedure for determining residues of methanesulfonate of m-aminobenzoic acid ethyl ester (MS-222) in fish muscle, homogenized tissue is extracted with distilled water, and proteins are removed by coagulation with trichloroacetic acid, centrifugation, and filtration. After careful pH adjustment of the filtrate, MS-222 is partitioned into benzene-ethyl ether and measured by alkali flame ionization gas chromatography. Tissues with known additions of 1-19 microgram MS-222/g were analyzed, with recoveries of 84-95%.", "contents": "Gas-liquid chromatographic determination of residues of methanesulfonate of n-aminobenzoic acid ethyl ester in fish. In this gas-liquid chromatographic procedure for determining residues of methanesulfonate of m-aminobenzoic acid ethyl ester (MS-222) in fish muscle, homogenized tissue is extracted with distilled water, and proteins are removed by coagulation with trichloroacetic acid, centrifugation, and filtration. After careful pH adjustment of the filtrate, MS-222 is partitioned into benzene-ethyl ether and measured by alkali flame ionization gas chromatography. Tissues with known additions of 1-19 microgram MS-222/g were analyzed, with recoveries of 84-95%."}
{"id": "PMID:197056", "title": "Analysis of fat-soluble vitamins. XVI. Antirachitic activity of 5,6-trans-vitamin D3 alone and in the presence of 5,6-cis-vitamin D3 resin, using chick bioassays.", "content": "Two biological assays were conducted in which the antirachitic activity in chicks of 5,6-trans-vitamin D3 added to feed is compared with that of 5,6-cis-vitamin D3. On the basis of the results obtained it is concluded that the relative potency of the trans isomer is, at the most, 5% and that the antirachitic activity of the trans isomer is not markedly enhanced (an increase to a relative potency of 16%, at the most) if the cis isomer is also included in the diet. The results are not conclusive on the inhibition or lack of inhibition of the antirachitic activity of 5,6-cis-vitamin D3 by the presence of 5,6-trans-vitamin D3 in the feed.", "contents": "Analysis of fat-soluble vitamins. XVI. Antirachitic activity of 5,6-trans-vitamin D3 alone and in the presence of 5,6-cis-vitamin D3 resin, using chick bioassays. Two biological assays were conducted in which the antirachitic activity in chicks of 5,6-trans-vitamin D3 added to feed is compared with that of 5,6-cis-vitamin D3. On the basis of the results obtained it is concluded that the relative potency of the trans isomer is, at the most, 5% and that the antirachitic activity of the trans isomer is not markedly enhanced (an increase to a relative potency of 16%, at the most) if the cis isomer is also included in the diet. The results are not conclusive on the inhibition or lack of inhibition of the antirachitic activity of 5,6-cis-vitamin D3 by the presence of 5,6-trans-vitamin D3 in the feed."}
{"id": "PMID:197057", "title": "Simple sensitive technique for detecting organochlorine pesticides on thin layer chromatograms.", "content": "Chlorinated hydrocarbon pesticides can be quickly detected using commercially available thin layer chromatographic plates dipped in an acetone solution of silver nitrate. The limits of detection are functions of the pesticide, adsorbent, developing system, and concentration of the silver nitrate in acetone solution. On exposure to ultraviolet light, 0.002 microgram 2,4,5-T produced clear darkening within 30 min on precoated silica gel plates (polyvinyl alcohol binder) coated with a solution of 0.1% silver nitrate in acetone. For this system, a 60-min detection period was necessary for a 0.05% coating solution. On the silica gel plates (polyvinyl alcohol binder, 0.1% silver nitrate), 0.02 microgram lindane is detected within 75 min. For alumina plates (polyvinyl alcohol binder, 0.1% silver nitrate), 0.025 microgram aldrin is detected within 10 min. Darkening of this plate prohibits the detection of 0.012 microgram aldrin. On silica gel plates (polyvinyl alcohol binder, 0.1% silver nitrate), 0.015 microgram aldrin can be detected within 45 min. The method described provides sensitivities equal to or exceeding literature values.", "contents": "Simple sensitive technique for detecting organochlorine pesticides on thin layer chromatograms. Chlorinated hydrocarbon pesticides can be quickly detected using commercially available thin layer chromatographic plates dipped in an acetone solution of silver nitrate. The limits of detection are functions of the pesticide, adsorbent, developing system, and concentration of the silver nitrate in acetone solution. On exposure to ultraviolet light, 0.002 microgram 2,4,5-T produced clear darkening within 30 min on precoated silica gel plates (polyvinyl alcohol binder) coated with a solution of 0.1% silver nitrate in acetone. For this system, a 60-min detection period was necessary for a 0.05% coating solution. On the silica gel plates (polyvinyl alcohol binder, 0.1% silver nitrate), 0.02 microgram lindane is detected within 75 min. For alumina plates (polyvinyl alcohol binder, 0.1% silver nitrate), 0.025 microgram aldrin is detected within 10 min. Darkening of this plate prohibits the detection of 0.012 microgram aldrin. On silica gel plates (polyvinyl alcohol binder, 0.1% silver nitrate), 0.015 microgram aldrin can be detected within 45 min. The method described provides sensitivities equal to or exceeding literature values."}
{"id": "PMID:197058", "title": "High pressure liquid chromatographic separation and identification of vitamins D2 and D3 in the presence of fat-soluble vitamins in dosage forms.", "content": "A simple and rapid qualitative method is described for determining the presence of vitamin D2 (ergocalciferol) and/or vitamin D3 (cholecalciferol) in various preparations by reverse phase high pressure liquid chromatography (HPLC). When both D2 and D3 are present, this method effectively separates and identifies each vitamin D form by its respective retention time. A significant difference between vitamins D2 and D3 exists in their antirachitic activity in poultry. Preparations can be tested rapidly by this method to ascertain that the correct D vitamin form has been added. Fat-soluble vitamins such as vitamins A, E, K1, and K3 do not interfere. Vitamins D2 and D3 were separated at the baseline in model preparations. As little as 2 ng each of vitamin D2 and vitamin D3 can be separated and identified.", "contents": "High pressure liquid chromatographic separation and identification of vitamins D2 and D3 in the presence of fat-soluble vitamins in dosage forms. A simple and rapid qualitative method is described for determining the presence of vitamin D2 (ergocalciferol) and/or vitamin D3 (cholecalciferol) in various preparations by reverse phase high pressure liquid chromatography (HPLC). When both D2 and D3 are present, this method effectively separates and identifies each vitamin D form by its respective retention time. A significant difference between vitamins D2 and D3 exists in their antirachitic activity in poultry. Preparations can be tested rapidly by this method to ascertain that the correct D vitamin form has been added. Fat-soluble vitamins such as vitamins A, E, K1, and K3 do not interfere. Vitamins D2 and D3 were separated at the baseline in model preparations. As little as 2 ng each of vitamin D2 and vitamin D3 can be separated and identified."}
{"id": "PMID:197059", "title": "Kinase replacement by a dehydrogenase for Escherichia coli glycerol utilization.", "content": "A mutant of Escherichia coli that employs a glycerol:nicotinamide adenine dinucleotide 2-oxidoreductase (EC 1.1.1.6), instead of adenosine 5'-triphosphate:glycerol 3-phosphotransferase (EC 2.7.1.30), as the first enzyme for the dissimilation of glycerol was constructed. This mutant, like the wild-type strain, still cannot grow anaerobically on glycerol without an exogenous hydrogen acceptor.", "contents": "Kinase replacement by a dehydrogenase for Escherichia coli glycerol utilization. A mutant of Escherichia coli that employs a glycerol:nicotinamide adenine dinucleotide 2-oxidoreductase (EC 1.1.1.6), instead of adenosine 5'-triphosphate:glycerol 3-phosphotransferase (EC 2.7.1.30), as the first enzyme for the dissimilation of glycerol was constructed. This mutant, like the wild-type strain, still cannot grow anaerobically on glycerol without an exogenous hydrogen acceptor."}
{"id": "PMID:197060", "title": "Effect of carbon source and the role of cyclic adenosine 3',5'-monophosphate on the Caulobacter cell cycle.", "content": "The expression of cell cycle events in Caulobacter crescentus CB13 has been shown to be associated with regulation of carbohydrate utilization. Growth on lactose and galactose depends on induction of specific enzymes. Prior growth on glucose results in a delay in enzyme expression and cell cycle arrest at the nonmotile, predivisional stage. Dibutyryl cyclic adenosine 3',5'-monophosphate (AMP) was shown to stimulate expression of the inducible enzymes and, thus, the initiation of the cell cycle. beta-Galactosidase-constitutive mutants did not exhibit a cell cycle arrest upon transfer of cultures from glucose to lactose. Furthermore, carbon source starvation results in accumulation of the cells at the predivisional stage. The cell cycle arrest therefore results from nutritional deprivation and is analogous to the general control system exhibited by yeast (Hartwell, Bacteriol. Rev. 38:164-198, 1974; Wolfner et al., J. Mol. Biol. 96:273-290, 1975), which coordinates cell cycle initiation with metabolic state. Transfer of C. crescentus CB13 from glucose to mannose did not result in a cell cycle arrest, and it was demonstrated that this carbon source is metabolized by constitutive enzymes. Growth on mannose, however, is stimulated by exogenous dibutyryl cyclic AMP without a concomitant increase in the specific activity of the mannose catabolic enzymes. The effect of cyclic AMP on growth on sugars metabolized by inducible enzymes, as well as on sugars metabolized by constitutive enzymes, may represent a regulatory system common to both types of sugar utilization, since they share features that differ from glucose utilization, namely, temperature-sensitive growth and low intracellular concentrations of cyclic guanosine 3',5'-monophosphate.", "contents": "Effect of carbon source and the role of cyclic adenosine 3',5'-monophosphate on the Caulobacter cell cycle. The expression of cell cycle events in Caulobacter crescentus CB13 has been shown to be associated with regulation of carbohydrate utilization. Growth on lactose and galactose depends on induction of specific enzymes. Prior growth on glucose results in a delay in enzyme expression and cell cycle arrest at the nonmotile, predivisional stage. Dibutyryl cyclic adenosine 3',5'-monophosphate (AMP) was shown to stimulate expression of the inducible enzymes and, thus, the initiation of the cell cycle. beta-Galactosidase-constitutive mutants did not exhibit a cell cycle arrest upon transfer of cultures from glucose to lactose. Furthermore, carbon source starvation results in accumulation of the cells at the predivisional stage. The cell cycle arrest therefore results from nutritional deprivation and is analogous to the general control system exhibited by yeast (Hartwell, Bacteriol. Rev. 38:164-198, 1974; Wolfner et al., J. Mol. Biol. 96:273-290, 1975), which coordinates cell cycle initiation with metabolic state. Transfer of C. crescentus CB13 from glucose to mannose did not result in a cell cycle arrest, and it was demonstrated that this carbon source is metabolized by constitutive enzymes. Growth on mannose, however, is stimulated by exogenous dibutyryl cyclic AMP without a concomitant increase in the specific activity of the mannose catabolic enzymes. The effect of cyclic AMP on growth on sugars metabolized by inducible enzymes, as well as on sugars metabolized by constitutive enzymes, may represent a regulatory system common to both types of sugar utilization, since they share features that differ from glucose utilization, namely, temperature-sensitive growth and low intracellular concentrations of cyclic guanosine 3',5'-monophosphate."}
{"id": "PMID:197061", "title": "A method for incorporating labeled lacithin into serum low density lipoproteins in vitro.", "content": "A sonicated dispersion of [14C]lecithin was incubated with high density lipoproteins (HDL) coupled to Sepharose. After washing the gels thoroughly with a buffer, the gels were incubated with low density lipoproteins (LDL); [14C]lecithin was transferred from the sonicated dispersion via HDL-Sepharose to the LDL. The LDL fraction thus prepared showed no contamination with lecithin dispersion or HDL. The lecithin:cholesterol  acyltransferase (LCAT) reaction could be completely inhibited during preparation, and the net recovery of radioactivity in LDL was 16% of that of the original lecithin dispersion. The [14C]lecithin in the washed HDL-Sepharose was shown to be a substrate of the LCAT reaction in vitro.", "contents": "A method for incorporating labeled lacithin into serum low density lipoproteins in vitro. A sonicated dispersion of [14C]lecithin was incubated with high density lipoproteins (HDL) coupled to Sepharose. After washing the gels thoroughly with a buffer, the gels were incubated with low density lipoproteins (LDL); [14C]lecithin was transferred from the sonicated dispersion via HDL-Sepharose to the LDL. The LDL fraction thus prepared showed no contamination with lecithin dispersion or HDL. The lecithin:cholesterol  acyltransferase (LCAT) reaction could be completely inhibited during preparation, and the net recovery of radioactivity in LDL was 16% of that of the original lecithin dispersion. The [14C]lecithin in the washed HDL-Sepharose was shown to be a substrate of the LCAT reaction in vitro."}
{"id": "PMID:197062", "title": "A latent collagenase from embryonic human skin explants.", "content": "Collagenase released from embryonic and adult human skin explants has been studied with special reference to the latency of the enzyme. 1) Embryonic human skin explants showed a much higher capacity for collagenase production than did adult skin, on the basis of unit weight of tissue. 2) Culture medium from embryonic skin explants contained latent collagenase at almost twice the concentration of the active form. No appreciable amount of latent enzyme was observed in the adult skin system. 3) The molecular weights of active and latent collagenases were about 40,000 and 50,000, respectively. 4) The latent collagenase was found to be activated by simple passage through a Sephadex G-50 column after adding NaI to a final concentration of 3 M. The degree of activation produced by this treatment was as high as that by limited proteolysis with trypsin. It was concluded that no activating enzyme system was involved in the activation of latent collagenase during NaI treatment, and that the latent enzyme was composed of an enzyme-inhibitor complex. 5) The physiological significance of latent enzyme in the regulation of collagenase activity in vivo is discussed.", "contents": "A latent collagenase from embryonic human skin explants. Collagenase released from embryonic and adult human skin explants has been studied with special reference to the latency of the enzyme. 1) Embryonic human skin explants showed a much higher capacity for collagenase production than did adult skin, on the basis of unit weight of tissue. 2) Culture medium from embryonic skin explants contained latent collagenase at almost twice the concentration of the active form. No appreciable amount of latent enzyme was observed in the adult skin system. 3) The molecular weights of active and latent collagenases were about 40,000 and 50,000, respectively. 4) The latent collagenase was found to be activated by simple passage through a Sephadex G-50 column after adding NaI to a final concentration of 3 M. The degree of activation produced by this treatment was as high as that by limited proteolysis with trypsin. It was concluded that no activating enzyme system was involved in the activation of latent collagenase during NaI treatment, and that the latent enzyme was composed of an enzyme-inhibitor complex. 5) The physiological significance of latent enzyme in the regulation of collagenase activity in vivo is discussed."}
{"id": "PMID:197065", "title": "Studies on pig serum lipoproteins. IV. Isolation and characterization of glycopeptides from pig serum low density lipoprotein.", "content": "Three glycopeptides were isolated from the pronase digest of the protein moiety of pig serum low density lipoprotein. The isolation procedure consisted of pronase digestion, gel filtration on Sephadex G-25 and G-50 columns, paper chromatography and DEAE-Sephadex A-50 column chromatography. Based on the carbohydrate analysis, the isolated glycopeptides were classified into two types. One type (GDI) consisted of mannose and N-acetylglucosamine residues in the molar ratio of 6:2 and had a molecular weight of about 2,300. The other type (GDII and GDIII) consisted of sialic acid, mannose, galactose, fucose, and N-acetylglucosamine residues in the molar ratio of 1:4:2:1:3 and 2:4:3:1:3, respectively. The molecular weights of GDII and GDIII were about 2,100 and 3,100, respectively. The results on the strong alkaline treatment of these glycopeptides suggested that all carbohydrate chains were linked to the peptide chains through N-acetylglucosaminyl-asparagine linkages. Of these glycopeptides and pig serum lipoproteins, only glycopeptide GDI and native LDL strongly interacted with concanavalin A.", "contents": "Studies on pig serum lipoproteins. IV. Isolation and characterization of glycopeptides from pig serum low density lipoprotein. Three glycopeptides were isolated from the pronase digest of the protein moiety of pig serum low density lipoprotein. The isolation procedure consisted of pronase digestion, gel filtration on Sephadex G-25 and G-50 columns, paper chromatography and DEAE-Sephadex A-50 column chromatography. Based on the carbohydrate analysis, the isolated glycopeptides were classified into two types. One type (GDI) consisted of mannose and N-acetylglucosamine residues in the molar ratio of 6:2 and had a molecular weight of about 2,300. The other type (GDII and GDIII) consisted of sialic acid, mannose, galactose, fucose, and N-acetylglucosamine residues in the molar ratio of 1:4:2:1:3 and 2:4:3:1:3, respectively. The molecular weights of GDII and GDIII were about 2,100 and 3,100, respectively. The results on the strong alkaline treatment of these glycopeptides suggested that all carbohydrate chains were linked to the peptide chains through N-acetylglucosaminyl-asparagine linkages. Of these glycopeptides and pig serum lipoproteins, only glycopeptide GDI and native LDL strongly interacted with concanavalin A."}
{"id": "PMID:197066", "title": "Phosphodiesterase-phosphomonoesterases from Fusarium moniliforme. VI. A modified method of purification and identification of isozymes.", "content": "Fusarium phosphodiesterase-phosphomonesterase was purified 1,630-fold with 19% yield from dried powder of the culture medium by a modified method consisting of seven steps. The purified preparation was shown to be devoid of inactive protein by disc electrophoresis. The preparation was homogeneous with respect to size as demonstrated by gel filtration, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ultracentrifugation. The molecular weights determined by gel filtration on Sephadex G-200 and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 106,000 and 100,000, respectively. The sedimentation coefficient at infinite dilution was 5.71 S. Isoelectric focusing of the purified preparation showed the presence of at least four isozymes with isoelectric points of 6.6, 6.3, 6.2, and 5.9.", "contents": "Phosphodiesterase-phosphomonoesterases from Fusarium moniliforme. VI. A modified method of purification and identification of isozymes. Fusarium phosphodiesterase-phosphomonesterase was purified 1,630-fold with 19% yield from dried powder of the culture medium by a modified method consisting of seven steps. The purified preparation was shown to be devoid of inactive protein by disc electrophoresis. The preparation was homogeneous with respect to size as demonstrated by gel filtration, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ultracentrifugation. The molecular weights determined by gel filtration on Sephadex G-200 and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 106,000 and 100,000, respectively. The sedimentation coefficient at infinite dilution was 5.71 S. Isoelectric focusing of the purified preparation showed the presence of at least four isozymes with isoelectric points of 6.6, 6.3, 6.2, and 5.9."}
{"id": "PMID:197068", "title": "The mechanism of action of citrinin on rabbit kidney alkaline phosphatase activity in vivo.", "content": "The effect of citrinin poisoning on rabbit kidney alkaline phosphatase was investigated. After seven days administration of citrinin (2 mg/kg body weight daily) the animals were sacrificed and the level of enzymes estimated in serum and kidney. Serum enzymes showed no variation in activity in the citrinin-treated animals, but in kidney, alkaline phosphatase activity decreased significantly. The decreased activity was mainly associated with the cytoplasmic fraction and in fractions Ib and II. The enzyme II obtained from citrinin-treated animal showed no kinetic difference in substrate specificity, inhibition by phenylalanine, phosphate, sodium-EDTA and Zn2+ ions, activation by Mg2+ ions, thermal inactivation and electrophoretic mobility to that of control Enzyme II. Immunological studies showed that the decrease in enzyme activity was due to existence of inactive enzyme protein. Hormones like cyclic AMP, prostaglandin E1 and parathyroid hormone reversed the decreased enzyme activity due to citrinin poisoning in mouse and rabbit. This study favours the possible existence of active and inactive forms of alkaline phosphatase in the system.", "contents": "The mechanism of action of citrinin on rabbit kidney alkaline phosphatase activity in vivo. The effect of citrinin poisoning on rabbit kidney alkaline phosphatase was investigated. After seven days administration of citrinin (2 mg/kg body weight daily) the animals were sacrificed and the level of enzymes estimated in serum and kidney. Serum enzymes showed no variation in activity in the citrinin-treated animals, but in kidney, alkaline phosphatase activity decreased significantly. The decreased activity was mainly associated with the cytoplasmic fraction and in fractions Ib and II. The enzyme II obtained from citrinin-treated animal showed no kinetic difference in substrate specificity, inhibition by phenylalanine, phosphate, sodium-EDTA and Zn2+ ions, activation by Mg2+ ions, thermal inactivation and electrophoretic mobility to that of control Enzyme II. Immunological studies showed that the decrease in enzyme activity was due to existence of inactive enzyme protein. Hormones like cyclic AMP, prostaglandin E1 and parathyroid hormone reversed the decreased enzyme activity due to citrinin poisoning in mouse and rabbit. This study favours the possible existence of active and inactive forms of alkaline phosphatase in the system."}
{"id": "PMID:197069", "title": "Intrinsic activity of guanosine 3',5'-monophosphate-dependent protein kinase similar to adenosine 3',5'-monophosphate-dependent protein kinase. I. Phosphorylation of histone fractions.", "content": "Guanosine 3',5'-monophosphate (cyclic GMP)-dependent protein kinase partially purified from silkworm pupae reacts preferentially with H1, H2A, and H2B histones but not with H3 AND H4 histones. However, the latter can serve as substrates in the presence of a stimulatory modulator as described by Kuo and Kuo (J. Biol. Chem. 251, 4283-4286 (1976)). With H2B histone as substrate high Mg2+ concentrations (50-100 mM) are necessary for the maximum rate of reaction. Although effects of the modulator and Mg2+ vary significantly with the histone fractions employed, analysis on the phosphorylation of histone fractions provides evidence that cyclic GMP-dependent protein kinase possesses an intrinsic activity that is similar to that of adenosine 3',5'-monophosphate-dependent protein kinase.", "contents": "Intrinsic activity of guanosine 3',5'-monophosphate-dependent protein kinase similar to adenosine 3',5'-monophosphate-dependent protein kinase. I. Phosphorylation of histone fractions. Guanosine 3',5'-monophosphate (cyclic GMP)-dependent protein kinase partially purified from silkworm pupae reacts preferentially with H1, H2A, and H2B histones but not with H3 AND H4 histones. However, the latter can serve as substrates in the presence of a stimulatory modulator as described by Kuo and Kuo (J. Biol. Chem. 251, 4283-4286 (1976)). With H2B histone as substrate high Mg2+ concentrations (50-100 mM) are necessary for the maximum rate of reaction. Although effects of the modulator and Mg2+ vary significantly with the histone fractions employed, analysis on the phosphorylation of histone fractions provides evidence that cyclic GMP-dependent protein kinase possesses an intrinsic activity that is similar to that of adenosine 3',5'-monophosphate-dependent protein kinase."}
{"id": "PMID:197070", "title": "Intrinsic activity of guanosine 3',5'-monophosphate-dependent protein kinase similar to adenosine 3',5'-monophosphate-dependent protein kinase. II. Phosphorylation of ribosomal proteins.", "content": "Guanosine 3',5'-monophosphate (cyclic GMP)-dependent protein kinase purified from silkworm pupae reacts with rat liver ribosomal proteins when a stimulatory modulator (Kuo, W.N. & Kuo, J.F. 1976) J. Biol. Chem. 251, 4283-4286) is added to the reaction mixture. Judging from autoradiogram of the radioactive proteins separated by electrophoresis on sodium dodecyl sulfate-polyacrylamide slab gel, the protein kinase utilizes the same proteins as those phosphorylated by adenosine 3',5'-monophosphate (cyclic AMP)-dependent protein kinase. Fingerprint maps of the tryptic phosphopeptides of radioactive ribosomal proteins, which are phosphorylated by these two classes of protein kinases, are very similar. These results suggest that cyclic GMP-dependent protein kinase possesses an intrinsic activity that is similar to that of cyclic AMP-dependent protein kinase.", "contents": "Intrinsic activity of guanosine 3',5'-monophosphate-dependent protein kinase similar to adenosine 3',5'-monophosphate-dependent protein kinase. II. Phosphorylation of ribosomal proteins. Guanosine 3',5'-monophosphate (cyclic GMP)-dependent protein kinase purified from silkworm pupae reacts with rat liver ribosomal proteins when a stimulatory modulator (Kuo, W.N. & Kuo, J.F. 1976) J. Biol. Chem. 251, 4283-4286) is added to the reaction mixture. Judging from autoradiogram of the radioactive proteins separated by electrophoresis on sodium dodecyl sulfate-polyacrylamide slab gel, the protein kinase utilizes the same proteins as those phosphorylated by adenosine 3',5'-monophosphate (cyclic AMP)-dependent protein kinase. Fingerprint maps of the tryptic phosphopeptides of radioactive ribosomal proteins, which are phosphorylated by these two classes of protein kinases, are very similar. These results suggest that cyclic GMP-dependent protein kinase possesses an intrinsic activity that is similar to that of cyclic AMP-dependent protein kinase."}
{"id": "PMID:197071", "title": "A carbon monoxide-binding hemoprotein formed by heme accumulation in Escherichia coli.", "content": "A CO-binding hemochrome was accumulated in Escherichia coli cells, when intracellular heme concentration was increased by aerobic incubation of resting cell suspensions with ALA. Reduced minus oxidized difference spectrum of the hemochrome showed peaks at 560, 530, and 430 nm and a shoulder at 575 nm. The peaks of CO reduced minus reduced difference spectrum were located at 572, 540, and 422 nm. The CO spectrum was similar to but not identical with the spectrum of cytochrome o, a known terminal oxidase in E. coli. SDS-polyacrylamide gel electrophoresis of the CO-binding hemochrome showed its molecular weight to be about 33,000. The hemochrome in crude cell-free extracts was oxidized by aeration and reduced by the addition of succinate or NADH. The reduction by succinate was inhibited by inhibitors of succinate dehydrogenase [EC 1.3.99.1], and the reduction by NADH was inhibited by 2-heptyl-4-hydroxy-quinolin-N-oxide, which is an inhibitor of electron transport in E. coli cells.", "contents": "A carbon monoxide-binding hemoprotein formed by heme accumulation in Escherichia coli. A CO-binding hemochrome was accumulated in Escherichia coli cells, when intracellular heme concentration was increased by aerobic incubation of resting cell suspensions with ALA. Reduced minus oxidized difference spectrum of the hemochrome showed peaks at 560, 530, and 430 nm and a shoulder at 575 nm. The peaks of CO reduced minus reduced difference spectrum were located at 572, 540, and 422 nm. The CO spectrum was similar to but not identical with the spectrum of cytochrome o, a known terminal oxidase in E. coli. SDS-polyacrylamide gel electrophoresis of the CO-binding hemochrome showed its molecular weight to be about 33,000. The hemochrome in crude cell-free extracts was oxidized by aeration and reduced by the addition of succinate or NADH. The reduction by succinate was inhibited by inhibitors of succinate dehydrogenase [EC 1.3.99.1], and the reduction by NADH was inhibited by 2-heptyl-4-hydroxy-quinolin-N-oxide, which is an inhibitor of electron transport in E. coli cells."}
{"id": "PMID:197072", "title": "Enzymatic oxidation of isethionate to sulfoacetaldehyde in bacterial extract.", "content": "Isethionate degradation in a bacterial extract was shown by the isolation of enzymes and by identification of an intermediate to take place in two steps; dehydrogenation to sulfoacetaldehyde and desulfonation leading to the formation of sulfite and acetate. The enzyme responsible for isethionate oxidation in the presence of FAD was particulate in nature and a solubilized preparation obtained by extraction with buffer of low ionic strength had oxidizing activities against only isethionate and n-butanol among compounds tested. The enzyme was inhibited by thiol and carbonyl reagents.", "contents": "Enzymatic oxidation of isethionate to sulfoacetaldehyde in bacterial extract. Isethionate degradation in a bacterial extract was shown by the isolation of enzymes and by identification of an intermediate to take place in two steps; dehydrogenation to sulfoacetaldehyde and desulfonation leading to the formation of sulfite and acetate. The enzyme responsible for isethionate oxidation in the presence of FAD was particulate in nature and a solubilized preparation obtained by extraction with buffer of low ionic strength had oxidizing activities against only isethionate and n-butanol among compounds tested. The enzyme was inhibited by thiol and carbonyl reagents."}
{"id": "PMID:197073", "title": "Oxidative pathway of choline to betaine in the soluble fraction prepared from Arthrobacter globiformis.", "content": "One strain of bacteria which showed high H2O2-generating activity was isolated from soil and characterized as Arthrobacter globiformis based on its morphological, nutritional, and physiological characteristics. The activities of H2O2 generation, NAD reduction and oxygen consumption in the bacterial cells were examined using choline, betaine aldehyde or betaine as substrate. Choline was oxidized to betaine aldehyde under aerobic conditions in a reaction coupled with H2O2 generation and oxygen consumption. On the other hand, betaine aldehyde seemed to be oxidized to betaine through two distinct oxidative reactions, H2O2 generation (oxygen consumption) under aerobic conditions and NAD reduction under either aerobic or anaerobic conditions. These enzyme activities were found in the supernatant fraction of the sonicated cell preparation.", "contents": "Oxidative pathway of choline to betaine in the soluble fraction prepared from Arthrobacter globiformis. One strain of bacteria which showed high H2O2-generating activity was isolated from soil and characterized as Arthrobacter globiformis based on its morphological, nutritional, and physiological characteristics. The activities of H2O2 generation, NAD reduction and oxygen consumption in the bacterial cells were examined using choline, betaine aldehyde or betaine as substrate. Choline was oxidized to betaine aldehyde under aerobic conditions in a reaction coupled with H2O2 generation and oxygen consumption. On the other hand, betaine aldehyde seemed to be oxidized to betaine through two distinct oxidative reactions, H2O2 generation (oxygen consumption) under aerobic conditions and NAD reduction under either aerobic or anaerobic conditions. These enzyme activities were found in the supernatant fraction of the sonicated cell preparation."}
{"id": "PMID:197075", "title": "Purification and properties of an acid phosphatase of Micrococcus denitrificans distinct from thiamine phosphate phosphatase.", "content": "To determine whether the acid phosphatase in Micrococcus denitrificans participates in hydrolysis of thiamine phosphate in the synthesis of thiamine pyrophosphate, acid phosphatase was purified 280-fold by conventional procedures, which removed thiamine phosphate phosphatase completely. Studies showed that this acid phosphatase is a different protein from thiamine phosphate phosphatase and that it has no binding site for thiamine phosphate on its active site.", "contents": "Purification and properties of an acid phosphatase of Micrococcus denitrificans distinct from thiamine phosphate phosphatase. To determine whether the acid phosphatase in Micrococcus denitrificans participates in hydrolysis of thiamine phosphate in the synthesis of thiamine pyrophosphate, acid phosphatase was purified 280-fold by conventional procedures, which removed thiamine phosphate phosphatase completely. Studies showed that this acid phosphatase is a different protein from thiamine phosphate phosphatase and that it has no binding site for thiamine phosphate on its active site."}
{"id": "PMID:197076", "title": "An ESR study of the Mn(II)-heavy meromyosin system.", "content": "The Mn(II)-heavy meromyosin system was studied by measuring the ESR spectrum of Mn(II). The temperature dependence of the line width parameter W(1, t) of a freshly prepared sample changes at around 7-10 degrees C, where W(1, t) is the reciprocal of the peak-to-peak height of the lowest magnetic field component of the hyperfine structure. It is shown that the change in the slope of W(1, t) at 7-10 degrees C is due to a change in the structure of Mn(II)-heavy meromyosin or a change in the interaction between Mn(II) and heavy meromyosin without ATP. This result is in accord with the recently reported observations that heavy meromysin ATPase activity showed different temperature dependence above and below 10 degrees C in the presence of Mn(II). The characteristics of the spectrum of the Mn(II)-heavy meromyosin system in the liquid state between 2 degrees C and 20 degrees C are compared with those of a frozen sample of Mn(II)-heavy meromyosin in a low temperature region (-50-0 degrees C) and with those of the lyophilized material. The forbidden transitions are observed, and hence the zero field splitting parameter can be obtained. It is 115 +/- 15 gauss at -50 degrees C, and decreases with increase of the temperature to 70 +/- 15 gauss at 20 degrees C.", "contents": "An ESR study of the Mn(II)-heavy meromyosin system. The Mn(II)-heavy meromyosin system was studied by measuring the ESR spectrum of Mn(II). The temperature dependence of the line width parameter W(1, t) of a freshly prepared sample changes at around 7-10 degrees C, where W(1, t) is the reciprocal of the peak-to-peak height of the lowest magnetic field component of the hyperfine structure. It is shown that the change in the slope of W(1, t) at 7-10 degrees C is due to a change in the structure of Mn(II)-heavy meromyosin or a change in the interaction between Mn(II) and heavy meromyosin without ATP. This result is in accord with the recently reported observations that heavy meromysin ATPase activity showed different temperature dependence above and below 10 degrees C in the presence of Mn(II). The characteristics of the spectrum of the Mn(II)-heavy meromyosin system in the liquid state between 2 degrees C and 20 degrees C are compared with those of a frozen sample of Mn(II)-heavy meromyosin in a low temperature region (-50-0 degrees C) and with those of the lyophilized material. The forbidden transitions are observed, and hence the zero field splitting parameter can be obtained. It is 115 +/- 15 gauss at -50 degrees C, and decreases with increase of the temperature to 70 +/- 15 gauss at 20 degrees C."}
{"id": "PMID:197078", "title": "Solubilization and separation of the glucagon receptor and adenylate cyclase in guanine nucleotide-sensitive states.", "content": "Adenylate cyclase in liver membranes was solubilized with Lubrol PX and partially purified by gel filtration. The partially purified enzyme was susceptible to activation by guanyl-5'-yl imidodiphosphate (Gpp(NH)p). Studies on the binding of [3H]Gpp(NH)p to various fractions eluted from the gels revealed that an upper limit of 1% of the Gpp(NH)p binding sites is associated with adenylate cyclase activity stimulated by the nucleotide. The glucagon receptor, pretagged with 125I-glucagon in the membranes, solubilized with Lubrol PX, and fractionated on the same gel columns, eluted in a peak fraction that overlaps with, but is separate from, adenylate cyclase in its Gpp(NH)p-stimulated form. Addition of GTP to the solubilized glucagon-receptor complex caused complete dissociation of the complex, as has been shown with the membrane-bound form of the complex. Since the GTP-sensitive form of the glucagon receptor complex separates from the Gpp(NH)p-sensitive form of adenylate cyclase, it is concluded that the receptor and the enzyme are separate molecules, each associated with a distinct nucleotide regulatory site or component. These findings are discussed in terms of the possible structure of the hormone-sensitive state of adenylate cyclase.", "contents": "Solubilization and separation of the glucagon receptor and adenylate cyclase in guanine nucleotide-sensitive states. Adenylate cyclase in liver membranes was solubilized with Lubrol PX and partially purified by gel filtration. The partially purified enzyme was susceptible to activation by guanyl-5'-yl imidodiphosphate (Gpp(NH)p). Studies on the binding of [3H]Gpp(NH)p to various fractions eluted from the gels revealed that an upper limit of 1% of the Gpp(NH)p binding sites is associated with adenylate cyclase activity stimulated by the nucleotide. The glucagon receptor, pretagged with 125I-glucagon in the membranes, solubilized with Lubrol PX, and fractionated on the same gel columns, eluted in a peak fraction that overlaps with, but is separate from, adenylate cyclase in its Gpp(NH)p-stimulated form. Addition of GTP to the solubilized glucagon-receptor complex caused complete dissociation of the complex, as has been shown with the membrane-bound form of the complex. Since the GTP-sensitive form of the glucagon receptor complex separates from the Gpp(NH)p-sensitive form of adenylate cyclase, it is concluded that the receptor and the enzyme are separate molecules, each associated with a distinct nucleotide regulatory site or component. These findings are discussed in terms of the possible structure of the hormone-sensitive state of adenylate cyclase."}
{"id": "PMID:197079", "title": "Stimulation of adenosine 3':5'-monophosphate formation by prostaglandins in human astrocytoma cells. Inhibition by nonsteroidal anti-inflammatory agents.", "content": "Prostaglandins (PG) of the E series and catecholamines stimulate adenosine 3':5'-monophosphate (cAMP) formation in human astrocytoma cells (1321N1). These two classes of effectors activated adenylate cyclase upon interaction with different receptor systems. No evidence for a mediatory role for PG in the action of catecholamines was found. PG interacted with 1321N1 cells with an order of potency of PGE1 = PGE2 greater than PGA1 greater than PGF2 alpha. The effect of combinations of the various PG indicated that all efficacious PG interacted with a common receptor. 7-Oxa-13-prostynoic acid and indomethacin were shown to be competitive inhibitors of the effect of PGE1 with Ki values of 4 and 150 micron, respectively. These two compounds did not inhibit the effect of isoproterenol. Polyphloretin phosphate caused a complex pattern of inhibition of the effects of PGE1 and at higher concentrations also inhibited the effects of isoproterenol. The mefenamate class of nonsteroidal anti-inflammatory agents was found to inhibit the effects of PGE1 with a potency order of meclofenamic acid greater than flufenamic acid = mefenamic acid. The inhibitory action of meclofenamic acid was complex involving specific, but partial, insurmountable antagonism of PGE1 as well as competitive inhibition of PGE1 effects. At higher concentrations of meclofenamic acid a nonspecific inhibition of the effects of both PGE1 and isoproterenol was observed. These studies suggest that the inhibition by nonsteroidal anti-inflammatory agents of the physiological effects of PGE1 in animals may occur, at least in part, at the level of adenylate cyclase. The possibility that multiple classes of adenylate cyclase-linked PGE receptors might exist in nature is discussed.", "contents": "Stimulation of adenosine 3':5'-monophosphate formation by prostaglandins in human astrocytoma cells. Inhibition by nonsteroidal anti-inflammatory agents. Prostaglandins (PG) of the E series and catecholamines stimulate adenosine 3':5'-monophosphate (cAMP) formation in human astrocytoma cells (1321N1). These two classes of effectors activated adenylate cyclase upon interaction with different receptor systems. No evidence for a mediatory role for PG in the action of catecholamines was found. PG interacted with 1321N1 cells with an order of potency of PGE1 = PGE2 greater than PGA1 greater than PGF2 alpha. The effect of combinations of the various PG indicated that all efficacious PG interacted with a common receptor. 7-Oxa-13-prostynoic acid and indomethacin were shown to be competitive inhibitors of the effect of PGE1 with Ki values of 4 and 150 micron, respectively. These two compounds did not inhibit the effect of isoproterenol. Polyphloretin phosphate caused a complex pattern of inhibition of the effects of PGE1 and at higher concentrations also inhibited the effects of isoproterenol. The mefenamate class of nonsteroidal anti-inflammatory agents was found to inhibit the effects of PGE1 with a potency order of meclofenamic acid greater than flufenamic acid = mefenamic acid. The inhibitory action of meclofenamic acid was complex involving specific, but partial, insurmountable antagonism of PGE1 as well as competitive inhibition of PGE1 effects. At higher concentrations of meclofenamic acid a nonspecific inhibition of the effects of both PGE1 and isoproterenol was observed. These studies suggest that the inhibition by nonsteroidal anti-inflammatory agents of the physiological effects of PGE1 in animals may occur, at least in part, at the level of adenylate cyclase. The possibility that multiple classes of adenylate cyclase-linked PGE receptors might exist in nature is discussed."}
{"id": "PMID:197081", "title": "On the structure of the prosthetic group of citrate (pro-3S)-lyase.", "content": "The prosthetic group of citrate (pro-3S)-lyase from Klebsiella aerogenes as well as Streptococcus diacetilactis was obtained eigher by beta elimination or pronase digestion of the enzyme and purified by DEAE-cellulose chromatography. The compound was shown to contain 3 mol of PO4, 2 mol of ribose, and 1 mol of sulfhydryl/mol of adenine. 5'-AMP and dephospho-CoA are components of the prosthetic group. The evidence obtained so far support our proposed structure of 3' (or 2') leads to 1''-(5''-phosphoribosyl)dephospho-CoA for the prosthetic group of citrate lyase. The presence of one phosphomonoester group in the compound isolated after beta elimination and the absence of the same in the compound isolated after pronase digestion indicated that the prosthetic group is attached to the enzyme through a phosphodiester bond. Analyses of the pyruvate released by beta elimination and subsequent acid hydrolysis of the peptide-bound prosthetic group and its degradation products showed that the phosphodiester linkage is between the hydroxyl group of a serine residue of the protein and the 5''-PO4 group of the second ribose.", "contents": "On the structure of the prosthetic group of citrate (pro-3S)-lyase. The prosthetic group of citrate (pro-3S)-lyase from Klebsiella aerogenes as well as Streptococcus diacetilactis was obtained eigher by beta elimination or pronase digestion of the enzyme and purified by DEAE-cellulose chromatography. The compound was shown to contain 3 mol of PO4, 2 mol of ribose, and 1 mol of sulfhydryl/mol of adenine. 5'-AMP and dephospho-CoA are components of the prosthetic group. The evidence obtained so far support our proposed structure of 3' (or 2') leads to 1''-(5''-phosphoribosyl)dephospho-CoA for the prosthetic group of citrate lyase. The presence of one phosphomonoester group in the compound isolated after beta elimination and the absence of the same in the compound isolated after pronase digestion indicated that the prosthetic group is attached to the enzyme through a phosphodiester bond. Analyses of the pyruvate released by beta elimination and subsequent acid hydrolysis of the peptide-bound prosthetic group and its degradation products showed that the phosphodiester linkage is between the hydroxyl group of a serine residue of the protein and the 5''-PO4 group of the second ribose."}
{"id": "PMID:197084", "title": "Ethionine and the phosphorylation of ribosomal protein S6.", "content": "Ribosome phosphorylation was studied by monitoring the phosphorylation state of small subunit protein S6 as visualized on two-dimensional electrophoretograms of ribosomal proteins isolated from rat liver. No phosphorylation of S6 was observed under conditions of ethionine-induced inhibition of protein synthesis. Moderate phosphorylation, detected as the appearance of S6 and four or five phosphorylated derivatives, was observed in saline-treated animals. Reversal of ethionine-induced inhibition of protein synthesis by treatment with adenine led to extensive phosphorylation of S6. A model for protein synthesis which includes requisite phosphorylation of ribosomes during initiation is proposed. Cyclic adenosine 3':5'-monophosphate concentration was significantly elevated in liver of both ethionine- and ethionine plus adenine-treated rats, relative to that of saline-treated animals.", "contents": "Ethionine and the phosphorylation of ribosomal protein S6. Ribosome phosphorylation was studied by monitoring the phosphorylation state of small subunit protein S6 as visualized on two-dimensional electrophoretograms of ribosomal proteins isolated from rat liver. No phosphorylation of S6 was observed under conditions of ethionine-induced inhibition of protein synthesis. Moderate phosphorylation, detected as the appearance of S6 and four or five phosphorylated derivatives, was observed in saline-treated animals. Reversal of ethionine-induced inhibition of protein synthesis by treatment with adenine led to extensive phosphorylation of S6. A model for protein synthesis which includes requisite phosphorylation of ribosomes during initiation is proposed. Cyclic adenosine 3':5'-monophosphate concentration was significantly elevated in liver of both ethionine- and ethionine plus adenine-treated rats, relative to that of saline-treated animals."}
{"id": "PMID:197085", "title": "Calcium stimulation of plasminogen activator secretion/production by swiss 3T3 cells.", "content": "Actively growing Swiss 3T3 cells secret high levels of plasminogen activator which decreases after the cells become confluent. In contrast, simian virus 40-transformed 3T3 cells secrete large amounts of plasminogen activator independent of cell density (Chou, I.-N., O'Donnel, S.P., Black, P.H., and Roblin, R.O. (1977) J. Cell. Physiol. 91, 31-38). These results suggest a correlation between active cell multiplication and plasminogen activator secretion in both 3T3 and simian virus-transformed 3T3 cells. The data reported herein indicate that treatment of both subconfluent and confluent Swiss 3T3 cells with high concentrations of Ca2+ (final 3.0 to 4.9 mM) increases the amounts of both secreted and cell-associated plasminogen activator in a dose-dependent manner. In addition, the ionophore A23187 (19 to 95 nM) in the presence of a normal level of Ca2+ (1.8 mM) stimulates both production and secretion of plasminogen activator from growing 3T3 cells. The Ca2+ stimulation of plasminogen activator production/secretion may be related to the mitogenic effect of Ca2+.", "contents": "Calcium stimulation of plasminogen activator secretion/production by swiss 3T3 cells. Actively growing Swiss 3T3 cells secret high levels of plasminogen activator which decreases after the cells become confluent. In contrast, simian virus 40-transformed 3T3 cells secrete large amounts of plasminogen activator independent of cell density (Chou, I.-N., O'Donnel, S.P., Black, P.H., and Roblin, R.O. (1977) J. Cell. Physiol. 91, 31-38). These results suggest a correlation between active cell multiplication and plasminogen activator secretion in both 3T3 and simian virus-transformed 3T3 cells. The data reported herein indicate that treatment of both subconfluent and confluent Swiss 3T3 cells with high concentrations of Ca2+ (final 3.0 to 4.9 mM) increases the amounts of both secreted and cell-associated plasminogen activator in a dose-dependent manner. In addition, the ionophore A23187 (19 to 95 nM) in the presence of a normal level of Ca2+ (1.8 mM) stimulates both production and secretion of plasminogen activator from growing 3T3 cells. The Ca2+ stimulation of plasminogen activator production/secretion may be related to the mitogenic effect of Ca2+."}
{"id": "PMID:197091", "title": "Guanosine 3':5'-monophosphate-dependent protein kinase from bovine lung. Subunit structure and characterization of the purified enzyme.", "content": "cGMP-dependent protein kinase from bovine lung has been purified to homogeneity using 8-(2-aminoethyl)-amino adenosine 3':5'-monophosphate/Sepharose. Conditions for adsorption of holoenzyme to the affinity chromatography media followed by competitive ligand elution with cGMP have been determined. The holoenzyme of 150,000 molecular weight is composed of two 74,000 molecular weight subunits which are linked in part by disulfide bridges. Two moles of cGMP are bound per mol of holoenzyme compatible with 1 mol of cGMP/monomer. Dissociation of subunits does not occur upon cGMP binding and protein kinase activation. cGMP-dependent protein kinase has an isoelectric point of 5.4 and a Stokes radius of 50 A. The enzyme is asymmetric with an f/f0 of 1.42 and an axial ratio of 7.4. Determination of enzyme activity at varying concentrations of ATP revealed that cGMP increased the Vmax for ATP without significant effect on the Km. The purified enzyme was maximally active at 5 mM Mg2+; other divalent cations could not substitute for Mg2+. In the presence of Mg2+, strong inhibitory effects of other cations were observed with Mn2+, greater than Zn2+, greater than Co2+ greater than Ca2+. Although maximal cGMP-dependence was observed at pH 5.7 to 7.0, basal activity rose at higher pH values to approach activity observed with cGMP. A molecular model comparing cGMP-dependent protein kinase with cAMP-dependnet protein kinase is presented.", "contents": "Guanosine 3':5'-monophosphate-dependent protein kinase from bovine lung. Subunit structure and characterization of the purified enzyme. cGMP-dependent protein kinase from bovine lung has been purified to homogeneity using 8-(2-aminoethyl)-amino adenosine 3':5'-monophosphate/Sepharose. Conditions for adsorption of holoenzyme to the affinity chromatography media followed by competitive ligand elution with cGMP have been determined. The holoenzyme of 150,000 molecular weight is composed of two 74,000 molecular weight subunits which are linked in part by disulfide bridges. Two moles of cGMP are bound per mol of holoenzyme compatible with 1 mol of cGMP/monomer. Dissociation of subunits does not occur upon cGMP binding and protein kinase activation. cGMP-dependent protein kinase has an isoelectric point of 5.4 and a Stokes radius of 50 A. The enzyme is asymmetric with an f/f0 of 1.42 and an axial ratio of 7.4. Determination of enzyme activity at varying concentrations of ATP revealed that cGMP increased the Vmax for ATP without significant effect on the Km. The purified enzyme was maximally active at 5 mM Mg2+; other divalent cations could not substitute for Mg2+. In the presence of Mg2+, strong inhibitory effects of other cations were observed with Mn2+, greater than Zn2+, greater than Co2+ greater than Ca2+. Although maximal cGMP-dependence was observed at pH 5.7 to 7.0, basal activity rose at higher pH values to approach activity observed with cGMP. A molecular model comparing cGMP-dependent protein kinase with cAMP-dependnet protein kinase is presented."}
{"id": "PMID:197093", "title": "Identification, characterization, and quantitative measurement of cyclic AMP receptor proteins in cytosol of various tissues using a photoaffinity ligand.", "content": "Two protein bands, present in cytosol fractions from each of seven rat tissues examined, specifically incorporated 32P-labeled 8-azidoadenosine 3':5'-monophosphate (8-N3-[32P]cAMP), a photoaffinity label for cAMP-binding sites. These proteins had apparent molecular weights of 47,000 and 54,000 on a sodium dodecyl sulfate-polyacrylamide gel electrophoresis system. These two proteins were characterized in three of the tissues, namely, heart, uterus, and liver, by the total amount of 8-N3-[32P]cAMP incorporation, by the dissociation constant (Kd) for 8-N3-[32P]cAMP, and by the nucleotide specific inhibition of 8-N3-[32P]cAMP incorporation. Several lines of evidence were obtained that the protein with an apparent molecular weight of 47,000 represents the regulatory subunit of a type I cAMP-dependent protein kinase, while the protein with an apparent molecular weight of 54,000 represents the regulatory subunit of a type II cAMP-dependent protein kinase. Almost all of the cAMP receptor protein found in the cytosol of these tissues, as measured by 8-N3-[32P]cAMP incorporation, was associated with these two protein kinases, in agreement with the idea that most effects of cAMP are mediated through protein kinases. The photoaffinity labeling with 8-N3-[32P]cAMP can be used to estimate quantitatively the amounts of regulatory subunit of type I and type II cAMP-dependent protein kinases in various tissues.", "contents": "Identification, characterization, and quantitative measurement of cyclic AMP receptor proteins in cytosol of various tissues using a photoaffinity ligand. Two protein bands, present in cytosol fractions from each of seven rat tissues examined, specifically incorporated 32P-labeled 8-azidoadenosine 3':5'-monophosphate (8-N3-[32P]cAMP), a photoaffinity label for cAMP-binding sites. These proteins had apparent molecular weights of 47,000 and 54,000 on a sodium dodecyl sulfate-polyacrylamide gel electrophoresis system. These two proteins were characterized in three of the tissues, namely, heart, uterus, and liver, by the total amount of 8-N3-[32P]cAMP incorporation, by the dissociation constant (Kd) for 8-N3-[32P]cAMP, and by the nucleotide specific inhibition of 8-N3-[32P]cAMP incorporation. Several lines of evidence were obtained that the protein with an apparent molecular weight of 47,000 represents the regulatory subunit of a type I cAMP-dependent protein kinase, while the protein with an apparent molecular weight of 54,000 represents the regulatory subunit of a type II cAMP-dependent protein kinase. Almost all of the cAMP receptor protein found in the cytosol of these tissues, as measured by 8-N3-[32P]cAMP incorporation, was associated with these two protein kinases, in agreement with the idea that most effects of cAMP are mediated through protein kinases. The photoaffinity labeling with 8-N3-[32P]cAMP can be used to estimate quantitatively the amounts of regulatory subunit of type I and type II cAMP-dependent protein kinases in various tissues."}
{"id": "PMID:197094", "title": "Altered absorption spectra of iso-1-cytochromes c from mutants of yeast.", "content": "Low temperature (-190 degrees) spectrophotometric recordings were made of mutant strains of the yeast Saccharomyces cerevisiae containing various altered sequences of iso-1-cytochromes c. All mutants with replacements of the tryptophan 64 residue had abnormal Calpha-bands, in which the alpha2-peaks were accentuated to various degrees by being more separated from the major alpha1-peaks and by making up a larger portion of the total Calpha-peak. The altered iso-1-cytochromes c included those having the normal tryptophan 64 replaced by phenylalanine, leucine, tyrosine, cysteine, serine, or glycine as well as those having replacements at position 64 and additional replacements at other sites. Tryptophan 64 in iso-1-cytochrome c, which corresponds to tryptophan 59 in vertebrate cytochromes c, appears to be an important residue for preserving the electronic environment of the heme group. It is uncertain, however, whether altered spectra are due specifically to the abnormal residues at position 64 or due to distorted tertiary structures caused by the replacements.", "contents": "Altered absorption spectra of iso-1-cytochromes c from mutants of yeast. Low temperature (-190 degrees) spectrophotometric recordings were made of mutant strains of the yeast Saccharomyces cerevisiae containing various altered sequences of iso-1-cytochromes c. All mutants with replacements of the tryptophan 64 residue had abnormal Calpha-bands, in which the alpha2-peaks were accentuated to various degrees by being more separated from the major alpha1-peaks and by making up a larger portion of the total Calpha-peak. The altered iso-1-cytochromes c included those having the normal tryptophan 64 replaced by phenylalanine, leucine, tyrosine, cysteine, serine, or glycine as well as those having replacements at position 64 and additional replacements at other sites. Tryptophan 64 in iso-1-cytochrome c, which corresponds to tryptophan 59 in vertebrate cytochromes c, appears to be an important residue for preserving the electronic environment of the heme group. It is uncertain, however, whether altered spectra are due specifically to the abnormal residues at position 64 or due to distorted tertiary structures caused by the replacements."}
{"id": "PMID:197095", "title": "Regulation of lipogenesis in isolated hepatocytes by triglyceride-rich lipoproteins.", "content": "Very low density lipoproteins, chylomicrons, and remnants caused, within an hour, significant inhibition of fatty acid synthesis but not cholesterol synthesis in hepatocytes isolated from meal-fed rats. In contrast, low density lipoproteins, high density lipoproteins, and the serum fraction of density greater than 1.21 failed to significantly inhibit either fatty acid or cholesterol synthesis within 1 h. The Scatchard plots of specific binding showed that rat and human very low density lipoproteins interact with the high affinity sites on the hepatocytes with the apparent dissociation constants of 64 and 106 nM, respectively. These data also indicated that each hepatocyte was capable of binding 6 X 10(5) molecules of very low density lipoproteins.", "contents": "Regulation of lipogenesis in isolated hepatocytes by triglyceride-rich lipoproteins. Very low density lipoproteins, chylomicrons, and remnants caused, within an hour, significant inhibition of fatty acid synthesis but not cholesterol synthesis in hepatocytes isolated from meal-fed rats. In contrast, low density lipoproteins, high density lipoproteins, and the serum fraction of density greater than 1.21 failed to significantly inhibit either fatty acid or cholesterol synthesis within 1 h. The Scatchard plots of specific binding showed that rat and human very low density lipoproteins interact with the high affinity sites on the hepatocytes with the apparent dissociation constants of 64 and 106 nM, respectively. These data also indicated that each hepatocyte was capable of binding 6 X 10(5) molecules of very low density lipoproteins."}
{"id": "PMID:197096", "title": "Study of autophosphorylation of isoenzymes of cyclic AMP-dependent protein kinases.", "content": "Type I and type II cyclic AMP-dependent protein kinases, present in the cytosol from each of five rat and two bovine tissues, were separated from one another by DEAE-cellulose column chromatography in order to study their possible autophosphorylation. In each of the tissues studied, autophosphorylation of the regulatory subunit of the cyclic AMP-dependent protein kinase by the catalytic subunit could be demonstrated with the type II enzyme but not with the type I enzyme.", "contents": "Study of autophosphorylation of isoenzymes of cyclic AMP-dependent protein kinases. Type I and type II cyclic AMP-dependent protein kinases, present in the cytosol from each of five rat and two bovine tissues, were separated from one another by DEAE-cellulose column chromatography in order to study their possible autophosphorylation. In each of the tissues studied, autophosphorylation of the regulatory subunit of the cyclic AMP-dependent protein kinase by the catalytic subunit could be demonstrated with the type II enzyme but not with the type I enzyme."}
{"id": "PMID:197101", "title": "UDP-glucuronate carboxy-lyase in cultured chondrocytes.", "content": "UDP-glucuronate carboxy-lyase has been demonstrated in chick chondrocytes in tissue culture. It occurs in the particulate fraction, and its activity is stimulated by exogenous NAD. The enzyme is allosterically activated by UDP-glucuronate and inhibited by UDP-xylose, n Values of 2.8 indicate positive cooperativity of at least three interacting sites on the enzyme. These data suggest that UDP-xylose concentration in chondrocytes is regulated by substrate activation and product inhibition of UDP-glucuronate carboxy-lyase. Activity levels of the enzyme during growth of the cells peak towards mid-log phase and decline thereafter, closely paralleling levels of chondroitin sulfate glycosyltransferases determined previously (Schwartz, N. B. (1976) J. Biol. Chem. 251, 3346-3351). Thus, it appears that during chondrocyte development a common mechanism governs induction of glycosyltransferases and of UDP-glucuronate carboxy-lyase.", "contents": "UDP-glucuronate carboxy-lyase in cultured chondrocytes. UDP-glucuronate carboxy-lyase has been demonstrated in chick chondrocytes in tissue culture. It occurs in the particulate fraction, and its activity is stimulated by exogenous NAD. The enzyme is allosterically activated by UDP-glucuronate and inhibited by UDP-xylose, n Values of 2.8 indicate positive cooperativity of at least three interacting sites on the enzyme. These data suggest that UDP-xylose concentration in chondrocytes is regulated by substrate activation and product inhibition of UDP-glucuronate carboxy-lyase. Activity levels of the enzyme during growth of the cells peak towards mid-log phase and decline thereafter, closely paralleling levels of chondroitin sulfate glycosyltransferases determined previously (Schwartz, N. B. (1976) J. Biol. Chem. 251, 3346-3351). Thus, it appears that during chondrocyte development a common mechanism governs induction of glycosyltransferases and of UDP-glucuronate carboxy-lyase."}
{"id": "PMID:197102", "title": "Liposome oxidation and erythrocyte lysis by enzymically generated superoxide and hydrogen peroxide.", "content": "Xanthine oxidase, acting on acetaldehyde under aerobic conditions, produces a flux of O2- and H2O2 which attacks artificial liposomes and washed human erythrocytes. The liposomes were peroxidized and the erythrocytes suffered oxidation of hemoglobin followed by lysis. The oxidation of hemoglobin followed by lysis. The oxidation of hemoglobin, within the exposed erythrocytes, could be largely prevented by prior conversion to carbon monoxyhemoglobin, without preventing lysis. Hemolysis thus appeared to be a consequence of direct oxidative attack on the cell stroma. The enzyme-generated flux of O2- and of H2O2 also inactivated the xanthine oxidase. Superoxide dismutase or catalase, present in the suspending medium, protected the liposomes against peroxidation, the erythrocytes against lysis, and the xanthine oxidase against inactivation. Scavengers of O2('deltag), such as histidine or 2,5-dimethylfuran, which do not react with O2- or H2O2, also prevented peroxidation of liposomes and lysis of erythrocytes when present at low concentrations. In contrast a scavenger of OH-, such as mannitol was ineffective at low concentrations and provided significant protection only at much higher concentrations. It is proposed that O2- and H2O2 cooperated in producing OH- and O2('deltag), which were the proximate causes of lipid peroxidation and of hemolysis.", "contents": "Liposome oxidation and erythrocyte lysis by enzymically generated superoxide and hydrogen peroxide. Xanthine oxidase, acting on acetaldehyde under aerobic conditions, produces a flux of O2- and H2O2 which attacks artificial liposomes and washed human erythrocytes. The liposomes were peroxidized and the erythrocytes suffered oxidation of hemoglobin followed by lysis. The oxidation of hemoglobin followed by lysis. The oxidation of hemoglobin, within the exposed erythrocytes, could be largely prevented by prior conversion to carbon monoxyhemoglobin, without preventing lysis. Hemolysis thus appeared to be a consequence of direct oxidative attack on the cell stroma. The enzyme-generated flux of O2- and of H2O2 also inactivated the xanthine oxidase. Superoxide dismutase or catalase, present in the suspending medium, protected the liposomes against peroxidation, the erythrocytes against lysis, and the xanthine oxidase against inactivation. Scavengers of O2('deltag), such as histidine or 2,5-dimethylfuran, which do not react with O2- or H2O2, also prevented peroxidation of liposomes and lysis of erythrocytes when present at low concentrations. In contrast a scavenger of OH-, such as mannitol was ineffective at low concentrations and provided significant protection only at much higher concentrations. It is proposed that O2- and H2O2 cooperated in producing OH- and O2('deltag), which were the proximate causes of lipid peroxidation and of hemolysis."}
{"id": "PMID:197106", "title": "Alterations of rat hepatic cholesterogenesis by heterologous lipoproteins.", "content": "Heterologous human lipoproteins were infused into rats in order to change acutely the lipoprotein pattern to a predominant kind and the effect on hepatic cholesterogenesis was subsequently observed. A 4-h intravenous infusion of human low density and very low density lipoproteins into rats produced a significant decrease in the incorporation of acetate into cholesterol in both liver slices and homogenates. An infusion of similar concentrations of human high density lipoprotein produced a significant increase in hepatic cholesterol synthesis. These infusions did not change mevalonate conversion to cholesterol in either the homogenates or slices. Concomitant with the changes in hepatic cholesterol synthesis were changes of similar magnitudes in the activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. These alterations in hepatic cholesterol synthesis were associated with significant changes in microsomal cholesterol content. There was a significant increase in hepatic cholesterol synthesis with the infusion of apoproteins of high density lipoprotein. The apoproteins of very low density lipoprotein had no effect on hepatic cholesterogenesis. These studies indicate that circulating lipoproteins modify hepatic cholesterol synthesis and that the apoproteins of these lipoproteins may themselves be important for this action.", "contents": "Alterations of rat hepatic cholesterogenesis by heterologous lipoproteins. Heterologous human lipoproteins were infused into rats in order to change acutely the lipoprotein pattern to a predominant kind and the effect on hepatic cholesterogenesis was subsequently observed. A 4-h intravenous infusion of human low density and very low density lipoproteins into rats produced a significant decrease in the incorporation of acetate into cholesterol in both liver slices and homogenates. An infusion of similar concentrations of human high density lipoprotein produced a significant increase in hepatic cholesterol synthesis. These infusions did not change mevalonate conversion to cholesterol in either the homogenates or slices. Concomitant with the changes in hepatic cholesterol synthesis were changes of similar magnitudes in the activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. These alterations in hepatic cholesterol synthesis were associated with significant changes in microsomal cholesterol content. There was a significant increase in hepatic cholesterol synthesis with the infusion of apoproteins of high density lipoprotein. The apoproteins of very low density lipoprotein had no effect on hepatic cholesterogenesis. These studies indicate that circulating lipoproteins modify hepatic cholesterol synthesis and that the apoproteins of these lipoproteins may themselves be important for this action."}
{"id": "PMID:197108", "title": "Immobilization of urea cycle enzymes. I. Characterization of immobilized carbamoylphosphate synthetase and ornithine carbamoyltransferase.", "content": "Carbamoylphosphate synthetase (EC 2.7.2.5) and ornithine carbamoyl-transferase (EC 2.1.3.3) extracted from frog liver were successfully immobilized on CNBr-activated Sepharose 4B. The immobilized preparation had a better stability towards heat. The apparent Michaelis constant values for N-acetylglutamate, ammonia, and ATP were not significantly changed by immobilization.", "contents": "Immobilization of urea cycle enzymes. I. Characterization of immobilized carbamoylphosphate synthetase and ornithine carbamoyltransferase. Carbamoylphosphate synthetase (EC 2.7.2.5) and ornithine carbamoyl-transferase (EC 2.1.3.3) extracted from frog liver were successfully immobilized on CNBr-activated Sepharose 4B. The immobilized preparation had a better stability towards heat. The apparent Michaelis constant values for N-acetylglutamate, ammonia, and ATP were not significantly changed by immobilization."}
{"id": "PMID:197109", "title": "Extraosseous accumulation of 99mTc phosphate tracers. Case report and review of reported causes.", "content": "A patient with a signet-ring-cell carcinoma of the stomach accumulating 99mTc methylene diphosphonate is described. Other conditions reported in the literature are reviewed.", "contents": "Extraosseous accumulation of 99mTc phosphate tracers. Case report and review of reported causes. A patient with a signet-ring-cell carcinoma of the stomach accumulating 99mTc methylene diphosphonate is described. Other conditions reported in the literature are reviewed."}
{"id": "PMID:197111", "title": "Hormonal regulation of initiation of DNA synthesis and of differentiated function in Y-1 adrenal cortical cells.", "content": "ACTH, 8-Br-cAMP, and serum deprivation arrested Y-1 functional mouse adrenal tumor cells in the G1 phase of the cell cycle. Though ACTH and 8-Br-cAMP treated cells were larger with increased macromolecular synthetic rates compared to cells arrested in G1 by serum removal, a similar 8- to 10-hours lag to initiation of DNA synthesis was observed after either ACTH or 8-Br-cAMP removal or after serum addition. After the 8- to 10-hour lag period, cells entered S phase exponentially. ACTH or 8-Br-cAMP opposed serum induced DNA synthesis initiation only when added prior to S. Once commitment to DNA synthesis occurred, ACTH or 8-Br-cAMP addition did not inhibit DNA synthesis although 8-Br-cAMP induced a secondary block in G2. Though ACTH and 8-Br-cAMP inhibited serum induced initiation of DNA synthesis and did not affect serum induced cellular hypertrophy, both substances increased the steroidogenic capacity of the cell. ACTH and 8-Br-cAMP thus appear to specifically oppose the stimulatory effects of serum on initiation of DNA synthesis while inducing the differentiated function of the cell.", "contents": "Hormonal regulation of initiation of DNA synthesis and of differentiated function in Y-1 adrenal cortical cells. ACTH, 8-Br-cAMP, and serum deprivation arrested Y-1 functional mouse adrenal tumor cells in the G1 phase of the cell cycle. Though ACTH and 8-Br-cAMP treated cells were larger with increased macromolecular synthetic rates compared to cells arrested in G1 by serum removal, a similar 8- to 10-hours lag to initiation of DNA synthesis was observed after either ACTH or 8-Br-cAMP removal or after serum addition. After the 8- to 10-hour lag period, cells entered S phase exponentially. ACTH or 8-Br-cAMP opposed serum induced DNA synthesis initiation only when added prior to S. Once commitment to DNA synthesis occurred, ACTH or 8-Br-cAMP addition did not inhibit DNA synthesis although 8-Br-cAMP induced a secondary block in G2. Though ACTH and 8-Br-cAMP inhibited serum induced initiation of DNA synthesis and did not affect serum induced cellular hypertrophy, both substances increased the steroidogenic capacity of the cell. ACTH and 8-Br-cAMP thus appear to specifically oppose the stimulatory effects of serum on initiation of DNA synthesis while inducing the differentiated function of the cell."}
{"id": "PMID:197113", "title": "The structure of syncytia induced by the phytoparasitic nematode Nacobbus aberrans in tomato roots, and the possible role of plasmodesmata in their nutrition.", "content": "The structure of syncytia induced within galls in tomato roots by the false root-knot nematode Nacobbus aberrans has been examined by light and electron microscopy. A syncytium develops by breakdown or individual cell walls, which allows movement of cytoplasmic contents between transformed cells. The wall breakdown takes place at pit fields, where the plasmodesmata may be protected from digestion until the surrounding wall is removed. Numerous sieve elements differentiate in the cells outside the syncytium. These sieve elements, and also plasmodesmata in pit fields, are demonstrated by fluorescence microscopy. The possibility of a symplastic pathway of solute movement from the phloem to the syncytium is suggested. A massive accumulation of starch occurs in the gall cells and syncytial cells, which may be related to the proliferation of phloem. Wall ingrowths typical of transfer cells are absent, and a comparative survey of the structure and mode of solute entry into nematode-transformed cells in which ingrowths are present or absent is presented.", "contents": "The structure of syncytia induced by the phytoparasitic nematode Nacobbus aberrans in tomato roots, and the possible role of plasmodesmata in their nutrition. The structure of syncytia induced within galls in tomato roots by the false root-knot nematode Nacobbus aberrans has been examined by light and electron microscopy. A syncytium develops by breakdown or individual cell walls, which allows movement of cytoplasmic contents between transformed cells. The wall breakdown takes place at pit fields, where the plasmodesmata may be protected from digestion until the surrounding wall is removed. Numerous sieve elements differentiate in the cells outside the syncytium. These sieve elements, and also plasmodesmata in pit fields, are demonstrated by fluorescence microscopy. The possibility of a symplastic pathway of solute movement from the phloem to the syncytium is suggested. A massive accumulation of starch occurs in the gall cells and syncytial cells, which may be related to the proliferation of phloem. Wall ingrowths typical of transfer cells are absent, and a comparative survey of the structure and mode of solute entry into nematode-transformed cells in which ingrowths are present or absent is presented."}
{"id": "PMID:197115", "title": "Method for the separation of organochlorine residues before gas-liquid chromatographic analysis.", "content": "The adsorption characteristics of alumina and silica for column chromatography have been assessed to develop a method, using a single solvent, for the separation of seventeen organochlorine residues into four eluates prior to gas-liquid chromatographic analysis. The effects on the adsorbents of thermal activation and subsequent deactivation with water, variation of column size and choice of eluents have been critically examined. The lipid capacity of the alumina and the effect of co-extracted materials from animal tissue upon the elution profile of the organochlorines have been determined.", "contents": "Method for the separation of organochlorine residues before gas-liquid chromatographic analysis. The adsorption characteristics of alumina and silica for column chromatography have been assessed to develop a method, using a single solvent, for the separation of seventeen organochlorine residues into four eluates prior to gas-liquid chromatographic analysis. The effects on the adsorbents of thermal activation and subsequent deactivation with water, variation of column size and choice of eluents have been critically examined. The lipid capacity of the alumina and the effect of co-extracted materials from animal tissue upon the elution profile of the organochlorines have been determined."}
{"id": "PMID:197116", "title": "Distribution of antibody to hepatitis A antigen in a population of commerical plasma doners.", "content": "Plasma samples from 245 regular plasma donors for Plasma Alliance, Inc. (Knoxville, Tenn.) were tested for the presence of antibody to hepatitis A antigen. Antibody was detected at an immune adherence hemagglutination titer of 1:10 or greater in 37% (91 of 245) of the donors. A statistically significant difference in the frequency of anti-hepatitis A was found between the 18- to 29-year-old group (30%) and the 30- to 49-year-old group (57%). No significant differences between whites and blacks or males afemales were observed. Eighty percent of the donors were in the age range of 18 to 29 years, whereas 48% of the higher-titered plasmas (1:1,000 or greater) were in the 30 to 49 age group. By preselection of donors, it would be possible to produce an immune serum globulin with a specific anti-hepatitis A titer.", "contents": "Distribution of antibody to hepatitis A antigen in a population of commerical plasma doners. Plasma samples from 245 regular plasma donors for Plasma Alliance, Inc. (Knoxville, Tenn.) were tested for the presence of antibody to hepatitis A antigen. Antibody was detected at an immune adherence hemagglutination titer of 1:10 or greater in 37% (91 of 245) of the donors. A statistically significant difference in the frequency of anti-hepatitis A was found between the 18- to 29-year-old group (30%) and the 30- to 49-year-old group (57%). No significant differences between whites and blacks or males afemales were observed. Eighty percent of the donors were in the age range of 18 to 29 years, whereas 48% of the higher-titered plasmas (1:1,000 or greater) were in the 30 to 49 age group. By preselection of donors, it would be possible to produce an immune serum globulin with a specific anti-hepatitis A titer."}
{"id": "PMID:197117", "title": "Pertussis outbreak in Austin and Travis County, Texas, 1975.", "content": "An outbreak of bacteriologically proven pertussis occurred in Austin and Travis County, Texas, over a 7-month period in 1975. Eighty persons were cultured for pertussis in our laboratory. A total of 62% of specimens from 34 individuals with suspected pertussis was positive for Bordetella pertussis. Diagnosis of acute cases by both culture and fluorescent antibody was attempted, and the correlation of the methods is given. Analyses of cases by age, sex, immunization status, and antibiotic treatment prior to culture are included in this report. Two asymptomatic, culture-positive adults were found.", "contents": "Pertussis outbreak in Austin and Travis County, Texas, 1975. An outbreak of bacteriologically proven pertussis occurred in Austin and Travis County, Texas, over a 7-month period in 1975. Eighty persons were cultured for pertussis in our laboratory. A total of 62% of specimens from 34 individuals with suspected pertussis was positive for Bordetella pertussis. Diagnosis of acute cases by both culture and fluorescent antibody was attempted, and the correlation of the methods is given. Analyses of cases by age, sex, immunization status, and antibiotic treatment prior to culture are included in this report. Two asymptomatic, culture-positive adults were found."}
{"id": "PMID:197118", "title": "Elimination of false-positive cytomegalovirus immunoglobulin M-fluorescent-antibody reactions with immunoglobulin M serum fractions.", "content": "The cytomegalovirus fluorescent-antibody test for immunoglobline M (IgM) antibody was found positive in seven of nine infants with congenital rubella infection, in addition to eight of eight infants with confirmed cytomegalovirus infection. When the test was repeated on IgM fractions of the same sera freed from IgG by ultracentrifugation, only negative reactions were observed in those from the rubella-infected infants, whereas IgM fractions from the cytomegalovirus-infected infants remained positive.", "contents": "Elimination of false-positive cytomegalovirus immunoglobulin M-fluorescent-antibody reactions with immunoglobulin M serum fractions. The cytomegalovirus fluorescent-antibody test for immunoglobline M (IgM) antibody was found positive in seven of nine infants with congenital rubella infection, in addition to eight of eight infants with confirmed cytomegalovirus infection. When the test was repeated on IgM fractions of the same sera freed from IgG by ultracentrifugation, only negative reactions were observed in those from the rubella-infected infants, whereas IgM fractions from the cytomegalovirus-infected infants remained positive."}
{"id": "PMID:197119", "title": "Micro-indirect hemagglutination test for detection of antibody against transmissible gastroenteritis virus of pigs.", "content": "A micro-indirect hemagglutination (IHA) test was developed for detecting antibody against transmissible gastroenteritis (TGE) virus of pigs. TGE virus propagated in swine kidney cell cultures was highly purified and concentrated by the combination of ammonium sulfate precipitation, treatment with fluorocarbon, and sucrose density gradient centrifugation. Tanned sheep erythrocytes were sensitized with purified virus for use in the IHA test. The results of testing 104 serum samples collected from pigs in the field indicated that the IHA antibody titers were approximately five times higher than those obtained by a serum neutralization test and that there was good correlation between the antibody titers determined by the two tests. High IHA antibody titers developed in pigs experimentally exposed to virulent TGE virus. Sensitized sheep erythrocytes were stable under long-term storage at 4 degrees C (at least for 50 days). The conclusions made are that the IHA test described is more sensitive than the serum neutralization test for the detection of TGE antibody and may be of value for serodiagnosis of TGE.", "contents": "Micro-indirect hemagglutination test for detection of antibody against transmissible gastroenteritis virus of pigs. A micro-indirect hemagglutination (IHA) test was developed for detecting antibody against transmissible gastroenteritis (TGE) virus of pigs. TGE virus propagated in swine kidney cell cultures was highly purified and concentrated by the combination of ammonium sulfate precipitation, treatment with fluorocarbon, and sucrose density gradient centrifugation. Tanned sheep erythrocytes were sensitized with purified virus for use in the IHA test. The results of testing 104 serum samples collected from pigs in the field indicated that the IHA antibody titers were approximately five times higher than those obtained by a serum neutralization test and that there was good correlation between the antibody titers determined by the two tests. High IHA antibody titers developed in pigs experimentally exposed to virulent TGE virus. Sensitized sheep erythrocytes were stable under long-term storage at 4 degrees C (at least for 50 days). The conclusions made are that the IHA test described is more sensitive than the serum neutralization test for the detection of TGE antibody and may be of value for serodiagnosis of TGE."}
{"id": "PMID:197120", "title": "Concentration of L-thyroxine and L-triiodothyronine specifically bound to nuclear receptors in rat liver and kidney. Quantitative evidence favoring a major role of T3 in thyroid hormone action.", "content": "To estimate the relative contribution of l-triiodothyronine (T(3)) and l-thyroxine (T(4)) to thyroidal effects, we have measured the concentration of iodothyronine bound to specific hepatic nuclear receptor sites by three different techniques: (a) specific radioimmunoassay after separation of T(3) and T(4) by preparative paper chromatography; (b) in vivo kinetic approaches as reported previously; and (c) isotopic equilibration. By these three methods, receptor concentration of T(3) and T(4) in liver was 0.51+/-0.19 (SD) and 0.08+/-0.06; 0.52+/-0.12 and 0.08+/-0.02; and 0.50+/-0.13 and 0.10+/-0.03 pmol/mg DNA, respectively. The percentage contribution of T(3) and T(4) to total receptor iodothyronine was thus 86.8+/-9.0 and 13.2+/-9.4; 86.3+/-3.5 and 13.7+/-3.5; and 83.7+/-5.6 and 16.3+/-5.6%, respectively. In kidney, specifically bound nuclear T(3) and T(4) were estimated both by isotopic equilibration and by in vivo kinetic techniques to be 0.28+/-0.11 and 0.03+/-0.01 pmol/mg DNA, respectively. Thus, T(3) constituted 89.4+/-3.2% of total receptor iodothyronine in this tissue. No other iodothyronines or analogs were bound to the nuclear sites in either tissue. Kidney and liver nuclear T(3) concentrations also were identical to values previously reported with in vivo kinetic techniques. Other studies from this laboratory have suggested that thyroid effect is related to the molar concentration of iodothyronine bound to specific nuclear sites, that the sites are similar in various tissues, and that iodothyronine in plasma is in equilibrium with nuclear T(3). If these relationships are assumed, T(3) contributes between 85 and 90% of thyroidal effects in the euthyroid rat. The remaining 10-15% of thyroidal effect appears to result from the intrinsic activity of T(4).", "contents": "Concentration of L-thyroxine and L-triiodothyronine specifically bound to nuclear receptors in rat liver and kidney. Quantitative evidence favoring a major role of T3 in thyroid hormone action. To estimate the relative contribution of l-triiodothyronine (T(3)) and l-thyroxine (T(4)) to thyroidal effects, we have measured the concentration of iodothyronine bound to specific hepatic nuclear receptor sites by three different techniques: (a) specific radioimmunoassay after separation of T(3) and T(4) by preparative paper chromatography; (b) in vivo kinetic approaches as reported previously; and (c) isotopic equilibration. By these three methods, receptor concentration of T(3) and T(4) in liver was 0.51+/-0.19 (SD) and 0.08+/-0.06; 0.52+/-0.12 and 0.08+/-0.02; and 0.50+/-0.13 and 0.10+/-0.03 pmol/mg DNA, respectively. The percentage contribution of T(3) and T(4) to total receptor iodothyronine was thus 86.8+/-9.0 and 13.2+/-9.4; 86.3+/-3.5 and 13.7+/-3.5; and 83.7+/-5.6 and 16.3+/-5.6%, respectively. In kidney, specifically bound nuclear T(3) and T(4) were estimated both by isotopic equilibration and by in vivo kinetic techniques to be 0.28+/-0.11 and 0.03+/-0.01 pmol/mg DNA, respectively. Thus, T(3) constituted 89.4+/-3.2% of total receptor iodothyronine in this tissue. No other iodothyronines or analogs were bound to the nuclear sites in either tissue. Kidney and liver nuclear T(3) concentrations also were identical to values previously reported with in vivo kinetic techniques. Other studies from this laboratory have suggested that thyroid effect is related to the molar concentration of iodothyronine bound to specific nuclear sites, that the sites are similar in various tissues, and that iodothyronine in plasma is in equilibrium with nuclear T(3). If these relationships are assumed, T(3) contributes between 85 and 90% of thyroidal effects in the euthyroid rat. The remaining 10-15% of thyroidal effect appears to result from the intrinsic activity of T(4)."}
{"id": "PMID:197121", "title": "The mitogenic effect of the lymphocytosis promoting factor from Bordetella pertussis on human lymphocytes.", "content": "The purified lymphocytosis promoting factor (LPF) from Bordetella pertussis was found to be a potent mitogen for peripheral blood lymphocytes (PBL) from normal adults as well as for cord blood lymphocytes. Proliferation occurred in autologous plasma or fetal calf serum, regardless of previous exposure to pertussis infection or immunization. Only one adult human serum, from a physician constantly working with B. pertussis, inhibited the mitogenic response to LPF and this serum was shown to contain precipitating antibody against LPF. The proliferative effect of LPF was characteristic of a \"nonspecific\" mitogen and not of antigen stimulation of sensitized cells.LPF, phytohemagglutinin, and concanavalin A were approximately equal in potency although variation occurred depending upon the cell donor. Experiments with lymphocyte subpopulations obtained by rosetting techniques employing sheep erythrocytes, mouse erythrocytes, and sheep erythrocytes coated with antibody and complement suggested the requirement of a multicellular system for LPF mitogencity.PBL from most patients with chronic lymphatic leukemia and lymphosarcoma cell leukemia were even less responsive to LPF than to phytohemagglutinin, whereas PBL from patients with lymphosarcoma usually responded to both mitogens. It can be inferred from the results of experiments with both normal and leukemic cells that LPF, which is a murine thymus-derived (T)-cell mitogen, is also a T-cell mitogen for human PBL. The exact cell requirement and mode of action, however, are as yet unknown.", "contents": "The mitogenic effect of the lymphocytosis promoting factor from Bordetella pertussis on human lymphocytes. The purified lymphocytosis promoting factor (LPF) from Bordetella pertussis was found to be a potent mitogen for peripheral blood lymphocytes (PBL) from normal adults as well as for cord blood lymphocytes. Proliferation occurred in autologous plasma or fetal calf serum, regardless of previous exposure to pertussis infection or immunization. Only one adult human serum, from a physician constantly working with B. pertussis, inhibited the mitogenic response to LPF and this serum was shown to contain precipitating antibody against LPF. The proliferative effect of LPF was characteristic of a \"nonspecific\" mitogen and not of antigen stimulation of sensitized cells.LPF, phytohemagglutinin, and concanavalin A were approximately equal in potency although variation occurred depending upon the cell donor. Experiments with lymphocyte subpopulations obtained by rosetting techniques employing sheep erythrocytes, mouse erythrocytes, and sheep erythrocytes coated with antibody and complement suggested the requirement of a multicellular system for LPF mitogencity.PBL from most patients with chronic lymphatic leukemia and lymphosarcoma cell leukemia were even less responsive to LPF than to phytohemagglutinin, whereas PBL from patients with lymphosarcoma usually responded to both mitogens. It can be inferred from the results of experiments with both normal and leukemic cells that LPF, which is a murine thymus-derived (T)-cell mitogen, is also a T-cell mitogen for human PBL. The exact cell requirement and mode of action, however, are as yet unknown."}
{"id": "PMID:197122", "title": "Stimulation of surfactant production by oxytocin-induced labor in the rabbit.", "content": "The respiratory distress syndrome is believed to be due to insufficient surfactant. It is known that there is a greater incidence of the respiratory distress syndrome among infants delivered by cesarean section before labor than among those delivered after labor at the same gestational age. The purpose of this study was to determine the effect of labor on the production of pulmonary surfactant. We measured the phospholipid content of lung lavage in newborn rabbits delivered by cesarean section before labor at 29, 30, and 31 (full-term) days gestation and after oxytocin-induced labor at 31 days. We also measured the activities of pulmonary cholinephosphate cytidylyltransferase and choline-phosphotransferase, enzymes involved in the de novo synthesis of phosphatidylcholine, the major component of surfactant. There was a two- to fourfold increase in the amount of lung lavage phospholipid during the first 6 h after birth. This was not dependent upon gestational age at delivery. There was a further two- to fourfold increase in the next 18 h which was, however, dependent upon gestational age. Labor increased the amount of lavage phospholipid from rabbits delivered at full term by 132%, 177%, and 50% at 3, 6, and 24 h after birth, respectively. There was a postnatal increase in the activity of cholinephosphate cytidylyltransferase. This was almost linear with time during the first 12 h, by which time essentially adult values were attained. Choline-phosphate cytidylyltransferase was not affected by labor. There was also a postnatal increase in the activity of cholinephosphotransferase but this was stimulated 86%, 59%, and 21% by labor at 0, 1, and 24 h after birth, respectively. These studies suggest that labor stimulates both the synthesis and secretion of surfactant in the immediate postnatal period and thus may be an important factor in the prevention of the respiratory distress syndrome of the newborn.", "contents": "Stimulation of surfactant production by oxytocin-induced labor in the rabbit. The respiratory distress syndrome is believed to be due to insufficient surfactant. It is known that there is a greater incidence of the respiratory distress syndrome among infants delivered by cesarean section before labor than among those delivered after labor at the same gestational age. The purpose of this study was to determine the effect of labor on the production of pulmonary surfactant. We measured the phospholipid content of lung lavage in newborn rabbits delivered by cesarean section before labor at 29, 30, and 31 (full-term) days gestation and after oxytocin-induced labor at 31 days. We also measured the activities of pulmonary cholinephosphate cytidylyltransferase and choline-phosphotransferase, enzymes involved in the de novo synthesis of phosphatidylcholine, the major component of surfactant. There was a two- to fourfold increase in the amount of lung lavage phospholipid during the first 6 h after birth. This was not dependent upon gestational age at delivery. There was a further two- to fourfold increase in the next 18 h which was, however, dependent upon gestational age. Labor increased the amount of lavage phospholipid from rabbits delivered at full term by 132%, 177%, and 50% at 3, 6, and 24 h after birth, respectively. There was a postnatal increase in the activity of cholinephosphate cytidylyltransferase. This was almost linear with time during the first 12 h, by which time essentially adult values were attained. Choline-phosphate cytidylyltransferase was not affected by labor. There was also a postnatal increase in the activity of cholinephosphotransferase but this was stimulated 86%, 59%, and 21% by labor at 0, 1, and 24 h after birth, respectively. These studies suggest that labor stimulates both the synthesis and secretion of surfactant in the immediate postnatal period and thus may be an important factor in the prevention of the respiratory distress syndrome of the newborn."}
{"id": "PMID:197123", "title": "Nephrogenous cyclic adenosine monophosphate as a parathyroid function test.", "content": "Nephrogenous cyclic AMP (NcAMP), total cyclic AMP excretion (UcAMP), and plasma immunoreactive parathyroid hormone (iPTH), determined with a multivalent antiserum, were prospectively measured in 55 control subjects, 57 patients with primary hyperparathyroidism (1 degrees HPT), and 10 patients with chronic hypoparathyroidism. In the group with 1 degrees HPT, NcAMP was elevated in 52 patients (91%), and similar elevations were noted in subgroups of 26 patients with mild (serum calcium </=10.7 mg/dl) or intermittent hypercalcemia, 19 patients with mild renal insufficiency (mean glomerular filtration rate, 64 ml/min), and 10 patients with moderate renal insufficiency (mean glomerular filtration rate, 43 ml/min). Plasma iPTH was increased in 41 patients (73%). The development of a parametric expression for UcAMP was found to be critically important in the clinical interpretation of results for total cAMP excretion. Because of renal impairment in a large number of patients, the absolute excretion rate of cAMP correlated poorly with the hyperparathyroid state. Expressed as a function of creatinine excretion, UcAMP was elevated in 81% of patients with 1 degrees HPT, but the nonparametric nature of the expression led to a number of interpretive difficulties. The expression of cAMP excretion as a function of glomerular filtration rate was developed on the basis of the unique features of cAMP clearance in man, and this expression, which provided elevated values in 51 (89%) of the patients with 1 degrees HPT, avoided entirely the inadequacies of alternative expressions. Results for NcAMP and UcAMP in nonazotemic and azotemic patients with hypoparathyroidism confirmed the validity of the measurements and the expressions employed.", "contents": "Nephrogenous cyclic adenosine monophosphate as a parathyroid function test. Nephrogenous cyclic AMP (NcAMP), total cyclic AMP excretion (UcAMP), and plasma immunoreactive parathyroid hormone (iPTH), determined with a multivalent antiserum, were prospectively measured in 55 control subjects, 57 patients with primary hyperparathyroidism (1 degrees HPT), and 10 patients with chronic hypoparathyroidism. In the group with 1 degrees HPT, NcAMP was elevated in 52 patients (91%), and similar elevations were noted in subgroups of 26 patients with mild (serum calcium </=10.7 mg/dl) or intermittent hypercalcemia, 19 patients with mild renal insufficiency (mean glomerular filtration rate, 64 ml/min), and 10 patients with moderate renal insufficiency (mean glomerular filtration rate, 43 ml/min). Plasma iPTH was increased in 41 patients (73%). The development of a parametric expression for UcAMP was found to be critically important in the clinical interpretation of results for total cAMP excretion. Because of renal impairment in a large number of patients, the absolute excretion rate of cAMP correlated poorly with the hyperparathyroid state. Expressed as a function of creatinine excretion, UcAMP was elevated in 81% of patients with 1 degrees HPT, but the nonparametric nature of the expression led to a number of interpretive difficulties. The expression of cAMP excretion as a function of glomerular filtration rate was developed on the basis of the unique features of cAMP clearance in man, and this expression, which provided elevated values in 51 (89%) of the patients with 1 degrees HPT, avoided entirely the inadequacies of alternative expressions. Results for NcAMP and UcAMP in nonazotemic and azotemic patients with hypoparathyroidism confirmed the validity of the measurements and the expressions employed."}
{"id": "PMID:197124", "title": "High density lipoprotein metabolism in man.", "content": "The turnover of (125)I-high density lipoprotein (HDL) was examined in a total of 14 studies in eight normal volunteers in an attempt to determine the metabolic relationship between apolipoproteins A-I (apoA-I) and A-II (apoA-II) of HDL and to define further some of the determinants of HDL metabolism. All subjects were first studied under conditions of an isocaloric balanced diet (40% fat, 40% carbohydrate). Four were then studied with an 80% carbohydrate diet, and two were studied while receiving nicotinic acid (1 g three times daily) and ingesting the same isocaloric balanced diet. The decay of autologous (125)I-HDL and the appearance of urinary radioactivity were followed for at least 2 wk in each study. ApoA-I and apoA-II were isolated by Sephadex G-200 chromatography from serial plasma samples in each study. The specific activities of these peptides were then measured directly. It was found that the decay of specific activity of apoA-I and apoA-II were parallel to one another in all studies. The mean half-life of the terminal portion of decay was 5.8 days during the studies with a balanced diet.Mathematical modeling of the decay of plasma radioactivity and appearance of urinary radioactivity was most consistent with a two-compartment model. One compartment is within the plasma and exchanges with a nonplasma component. Catabolism occurs from both of these compartments. With a balanced isocaloric diet, the mean synthetic rate for HDL protein was 8.51 mg/kg per day. HDL synthesis was not altered by the high carbohydrate diet and was only slightly decreased by nicotinic acid treatment. These perturbations had effects on HDL catabolic pathways that were reciprocal in many respects. With an 80% carbohydrate diet, the rate of catabolism from the plasma compartment rose by a mean of 39.1%; with nicotinic acid treatment, it fell by 42.2%. Changes in the rate of catabolism from the second compartment were generally opposite those in the rate of catabolism from the plasma compartment, suggesting that these two catabolic pathways may be reciprocally regulated.", "contents": "High density lipoprotein metabolism in man. The turnover of (125)I-high density lipoprotein (HDL) was examined in a total of 14 studies in eight normal volunteers in an attempt to determine the metabolic relationship between apolipoproteins A-I (apoA-I) and A-II (apoA-II) of HDL and to define further some of the determinants of HDL metabolism. All subjects were first studied under conditions of an isocaloric balanced diet (40% fat, 40% carbohydrate). Four were then studied with an 80% carbohydrate diet, and two were studied while receiving nicotinic acid (1 g three times daily) and ingesting the same isocaloric balanced diet. The decay of autologous (125)I-HDL and the appearance of urinary radioactivity were followed for at least 2 wk in each study. ApoA-I and apoA-II were isolated by Sephadex G-200 chromatography from serial plasma samples in each study. The specific activities of these peptides were then measured directly. It was found that the decay of specific activity of apoA-I and apoA-II were parallel to one another in all studies. The mean half-life of the terminal portion of decay was 5.8 days during the studies with a balanced diet.Mathematical modeling of the decay of plasma radioactivity and appearance of urinary radioactivity was most consistent with a two-compartment model. One compartment is within the plasma and exchanges with a nonplasma component. Catabolism occurs from both of these compartments. With a balanced isocaloric diet, the mean synthetic rate for HDL protein was 8.51 mg/kg per day. HDL synthesis was not altered by the high carbohydrate diet and was only slightly decreased by nicotinic acid treatment. These perturbations had effects on HDL catabolic pathways that were reciprocal in many respects. With an 80% carbohydrate diet, the rate of catabolism from the plasma compartment rose by a mean of 39.1%; with nicotinic acid treatment, it fell by 42.2%. Changes in the rate of catabolism from the second compartment were generally opposite those in the rate of catabolism from the plasma compartment, suggesting that these two catabolic pathways may be reciprocally regulated."}
{"id": "PMID:197125", "title": "Regulation of rabbit myometrial alpha adrenergic receptors by estrogen and progesterone.", "content": "The effects of estrogen and progesterone on uterine alpha-adrenergic receptors were investigated by direct receptor-binding studies. Immature female rabbits were primed with estrogen by intramuscular injections for 4 days. Other rabbits were primed with progesterone by injections of estrogen for 4 days followed by injections of progesterone for 4 days. The alpha adrenergic antagonist, [3H]dihydroergocryptine, was used to directly assess the number and affinity of alpha adrenergic receptors in membranes derived from estrogen-and progesterone-primed uteri. Membranes from estrogen-primed uteri contained 257 +/- 52 fmol of [3H]dihydroergocryptine-binding sites per mg protein whereas membranes from progesterone-primed uteri contained 83 +/- 11 fmol of of binding sites per mg protein. This reduction of alpha adrenergic receptor-binding sites by progesterone was statistically significant (P less than 0.02). In contrast, no significant difference in the binding site affinity was observed between the estrogen- and progesterone-primed groups. The progesterone-induced decrease in the number of uterine alpha adrenergic receptors provides a potential explanation for the reduced alpha adrenergic contractile response to epinephrine in the progesterone-primed myometrium.", "contents": "Regulation of rabbit myometrial alpha adrenergic receptors by estrogen and progesterone. The effects of estrogen and progesterone on uterine alpha-adrenergic receptors were investigated by direct receptor-binding studies. Immature female rabbits were primed with estrogen by intramuscular injections for 4 days. Other rabbits were primed with progesterone by injections of estrogen for 4 days followed by injections of progesterone for 4 days. The alpha adrenergic antagonist, [3H]dihydroergocryptine, was used to directly assess the number and affinity of alpha adrenergic receptors in membranes derived from estrogen-and progesterone-primed uteri. Membranes from estrogen-primed uteri contained 257 +/- 52 fmol of [3H]dihydroergocryptine-binding sites per mg protein whereas membranes from progesterone-primed uteri contained 83 +/- 11 fmol of of binding sites per mg protein. This reduction of alpha adrenergic receptor-binding sites by progesterone was statistically significant (P less than 0.02). In contrast, no significant difference in the binding site affinity was observed between the estrogen- and progesterone-primed groups. The progesterone-induced decrease in the number of uterine alpha adrenergic receptors provides a potential explanation for the reduced alpha adrenergic contractile response to epinephrine in the progesterone-primed myometrium."}
{"id": "PMID:197126", "title": "Immune complexes in congenital and natal cytomegalovirus infections of man.", "content": "The occurrence of circulating immune complexes was investigated in 31 patients with cytomegalovirus infection (29 infected in utero and 2 with natal infection) and 34 uninfected controls. Anti-complementary activity above 1:20 occurred in 34% (29/86) of the sera tested from the infected group in contrast to 7.5% (3/40) in the controls (P < 0.005). When assayed by means of a lymphoblastoid cell line (Raji cell test), the reactivity in these groups was 45 (39/86) and 2.7% (1/36), respectively (P < 0.001). Correlation of results between these two complement-dependent assays occurred in 75% of samples collected from the infected group. Frequency of reactivity was higher in severe intrauterine infection and during the 1st yr of life paralleling the patterns of viral excretion and humoral immune responses. Physicochemical characterization demonstrated that reactive substances in sera were acid-dissociable and, in one sample tested, contained 7S IgG antibodies with cytomegalovirus (CMV) specificity. Circulating immune complexes were heavier (18-22S) in sick, as opposed to subclinically CMV-infected patients, in whom intermediate size complexes (12-16S) were found. In three of four symptomatic patients whose demise was due to severe congenital infection, granular deposits of immunoglobulins and C3 were detected in a pattern typical of immune complexes along the glomerular basal membrane of the glomeruli. Whether or not circulation and deposition of heavier immune complexes contributed to the adverse clinical outcome is unresolved. Because of the high incidence of both congenital and natal CMV infections, definition of the pathogenetic potentials of both heavy and intermediate size immune complexes is required to design more effective therapeutic measures.", "contents": "Immune complexes in congenital and natal cytomegalovirus infections of man. The occurrence of circulating immune complexes was investigated in 31 patients with cytomegalovirus infection (29 infected in utero and 2 with natal infection) and 34 uninfected controls. Anti-complementary activity above 1:20 occurred in 34% (29/86) of the sera tested from the infected group in contrast to 7.5% (3/40) in the controls (P < 0.005). When assayed by means of a lymphoblastoid cell line (Raji cell test), the reactivity in these groups was 45 (39/86) and 2.7% (1/36), respectively (P < 0.001). Correlation of results between these two complement-dependent assays occurred in 75% of samples collected from the infected group. Frequency of reactivity was higher in severe intrauterine infection and during the 1st yr of life paralleling the patterns of viral excretion and humoral immune responses. Physicochemical characterization demonstrated that reactive substances in sera were acid-dissociable and, in one sample tested, contained 7S IgG antibodies with cytomegalovirus (CMV) specificity. Circulating immune complexes were heavier (18-22S) in sick, as opposed to subclinically CMV-infected patients, in whom intermediate size complexes (12-16S) were found. In three of four symptomatic patients whose demise was due to severe congenital infection, granular deposits of immunoglobulins and C3 were detected in a pattern typical of immune complexes along the glomerular basal membrane of the glomeruli. Whether or not circulation and deposition of heavier immune complexes contributed to the adverse clinical outcome is unresolved. Because of the high incidence of both congenital and natal CMV infections, definition of the pathogenetic potentials of both heavy and intermediate size immune complexes is required to design more effective therapeutic measures."}
{"id": "PMID:197127", "title": "The interaction of heparin with an apoprotein of human very low density lipoprotein.", "content": "An arginine-rich apoprotein obtained from human triglyceride-rich lipoprotein was isolated on a heparin affinity column when either the aqueousor urea-soluble apoproteins were applied to the column. Of all the aqueous- or urea-soluble apoproteins, only this arginine-rich protein exhibited a binding affinity to heparin. This protein was eluted from the column at sodium chloride concentrations above 0.35 M in the absence of urea and between 0.17-0.2 M when isolated in urea. The protein has been characterized by amino acid analysis, immunoelectrophoresis, dodecyl sulfate polyacrylamide electrophoresis, isoelectric focusing, and NH(2)-terminal analysis. It has the same amino acid composition, NH(2)-terminal, and molecular weight as previously described for human arginine-rich apoprotein. The triglyceride-rich lipoproteins of fasting normal humans were eluted as two fractions when applied to the heparin affinity column. A small amount was eluted in the unbound fraction and this species contained virtually no arginine-rich apoprotein. The bulk of the triglyceride-rich lipoproteins eluted in the bound fraction and contained appreciable amounts of arginine-rich apoprotein. The bound lipoproteins had more cholesterol and cholesterol ester and less triglyceride than the unbound. The isolated arginine-rich apoprotein was derivatized with phenylglyoxal with a resulting alteration of 75% of the arginine residues. This modified apoprotein did not bind to the heparin affinity column. Similar treatment of the whole triglyceride-rich lipoprotein produced a lipoprotein that was totally eluted in the unbound fraction.", "contents": "The interaction of heparin with an apoprotein of human very low density lipoprotein. An arginine-rich apoprotein obtained from human triglyceride-rich lipoprotein was isolated on a heparin affinity column when either the aqueousor urea-soluble apoproteins were applied to the column. Of all the aqueous- or urea-soluble apoproteins, only this arginine-rich protein exhibited a binding affinity to heparin. This protein was eluted from the column at sodium chloride concentrations above 0.35 M in the absence of urea and between 0.17-0.2 M when isolated in urea. The protein has been characterized by amino acid analysis, immunoelectrophoresis, dodecyl sulfate polyacrylamide electrophoresis, isoelectric focusing, and NH(2)-terminal analysis. It has the same amino acid composition, NH(2)-terminal, and molecular weight as previously described for human arginine-rich apoprotein. The triglyceride-rich lipoproteins of fasting normal humans were eluted as two fractions when applied to the heparin affinity column. A small amount was eluted in the unbound fraction and this species contained virtually no arginine-rich apoprotein. The bulk of the triglyceride-rich lipoproteins eluted in the bound fraction and contained appreciable amounts of arginine-rich apoprotein. The bound lipoproteins had more cholesterol and cholesterol ester and less triglyceride than the unbound. The isolated arginine-rich apoprotein was derivatized with phenylglyoxal with a resulting alteration of 75% of the arginine residues. This modified apoprotein did not bind to the heparin affinity column. Similar treatment of the whole triglyceride-rich lipoprotein produced a lipoprotein that was totally eluted in the unbound fraction."}
{"id": "PMID:197129", "title": "The alcoholic's perception of the ward as a predictor of aftercare attendance.", "content": "The present study attempted to determine whether attendance in aftercare services could be predicted from the alcoholic's perception of the inpatient ward environment. Thirty-five Ss who completed inpatient treatment and were eligible for outpatient group therapy were followed up 3 months after discharge. One factor of the Ward Atmosphere Scale, autonomy, significantly differentiated attenders (N = 13) from nonattenders (N = 22); attenders perceived more autonomy on the ward than did nonattenders. Two additional factors, aggression and insight, also differentiated the groups, although not to a statistically significant degree. Attenders were found to perceive more encouragement by the staff to express openly their angry feelings and to share their personal selves with others than were nonattenders.", "contents": "The alcoholic's perception of the ward as a predictor of aftercare attendance. The present study attempted to determine whether attendance in aftercare services could be predicted from the alcoholic's perception of the inpatient ward environment. Thirty-five Ss who completed inpatient treatment and were eligible for outpatient group therapy were followed up 3 months after discharge. One factor of the Ward Atmosphere Scale, autonomy, significantly differentiated attenders (N = 13) from nonattenders (N = 22); attenders perceived more autonomy on the ward than did nonattenders. Two additional factors, aggression and insight, also differentiated the groups, although not to a statistically significant degree. Attenders were found to perceive more encouragement by the staff to express openly their angry feelings and to share their personal selves with others than were nonattenders."}
{"id": "PMID:197128", "title": "Human lung tissue and anaphylaxis. Evidence that cyclic nucleotides modulate the immunologic release of mediators through effects on microtubular assembly.", "content": "The addition of specific antigen to IgE-sensitized human lung tissue causes the secretion of the mediators histamine and slow-reacting substance of anaphylaxis. The mechanisms by which increased levels of cyclic AMP suppress and increased levels of cyclic GMP enhance this secretory process were studied. Colchicine, an agent which disrupts many secretory reactions by binding to microtubules in their disassembled 6S form, was a relatively ineffective inhibitor of the antigen-induced release of mediators unless lung fragments were incubated at 4 degrees C for 60 min to induce microtubular disassembly. As colchicine appeared to inhibit the immunologic secretion of mediators from human lung tissue most effectively after microtubular disassembly, the capacity of colchicine to modulate the release reaction indicated the state of microtubular assembly; inhibition by colchicine signaled a shift to the colchicine-sensitive 6S subunits whereas failure to inhibit suggested maintenance in the colchicine-resistant polymerized state.Exogenously added 8-Bromo-cyclic GMP prevented low temperature-facilitated colchicine suppression of mediator release suggesting that increased levels of cyclic GMP stabilize polymerized microtubules. Transiently increased cyclic AMP concentrations, either exogenously added as 8-Bromo-cyclic AMP or endogenously produced by isoproterenol, promoted colchicine suppression of mediator release suggesting that microtubular disassembly was produced. Direct measurement of cyclic AMP levels revealed parallel kinetics after isoproterenol stimulation between control and colchicine-treated lung fragments. The requirement for functional microtubules in the release reaction may occur after the antigen IgE-stimulated activation of a serine esterase, energy utilization, and an intracellular calcium requirement. The mechanism by which cyclic nucleotides influence microtubular assembly is postulated to involve the degree of phosphorylation-dephosphorylation of microtubules.", "contents": "Human lung tissue and anaphylaxis. Evidence that cyclic nucleotides modulate the immunologic release of mediators through effects on microtubular assembly. The addition of specific antigen to IgE-sensitized human lung tissue causes the secretion of the mediators histamine and slow-reacting substance of anaphylaxis. The mechanisms by which increased levels of cyclic AMP suppress and increased levels of cyclic GMP enhance this secretory process were studied. Colchicine, an agent which disrupts many secretory reactions by binding to microtubules in their disassembled 6S form, was a relatively ineffective inhibitor of the antigen-induced release of mediators unless lung fragments were incubated at 4 degrees C for 60 min to induce microtubular disassembly. As colchicine appeared to inhibit the immunologic secretion of mediators from human lung tissue most effectively after microtubular disassembly, the capacity of colchicine to modulate the release reaction indicated the state of microtubular assembly; inhibition by colchicine signaled a shift to the colchicine-sensitive 6S subunits whereas failure to inhibit suggested maintenance in the colchicine-resistant polymerized state.Exogenously added 8-Bromo-cyclic GMP prevented low temperature-facilitated colchicine suppression of mediator release suggesting that increased levels of cyclic GMP stabilize polymerized microtubules. Transiently increased cyclic AMP concentrations, either exogenously added as 8-Bromo-cyclic AMP or endogenously produced by isoproterenol, promoted colchicine suppression of mediator release suggesting that microtubular disassembly was produced. Direct measurement of cyclic AMP levels revealed parallel kinetics after isoproterenol stimulation between control and colchicine-treated lung fragments. The requirement for functional microtubules in the release reaction may occur after the antigen IgE-stimulated activation of a serine esterase, energy utilization, and an intracellular calcium requirement. The mechanism by which cyclic nucleotides influence microtubular assembly is postulated to involve the degree of phosphorylation-dephosphorylation of microtubules."}
{"id": "PMID:197130", "title": "Neural substrate for brain stimulation reward in the rat: cathodal and anodal strength-duration properties.", "content": "The trade-off between current strength and duration of a stimulating pulse was studied for the rewarding and priming effects of brain stimulation reward (BSR). With cathodal pulses, strenght-duration functions for BSR had chronaxies of .8-3 msec. No differences were observed between the results for rewarding and priming effects. With anodal pulses. strength-duration curves were parallel to the cathodal curves at pulse durations of .1-5 msec, but at pulse durations greater than 5 msec the anodal curves showed a greater drop in required current intensity than did the cathodal curves. The parallel portion of the anodal curves was interpreted as due to anode-make excitation, and the drop at longer pulse durations was interpreted as due to anode-break excitation. Cathodal strength-duration functions for the motor effect elicited through the BSR electrodes had chronaxies of .15-.48 msec. Measurements of the latency of the muscle twitch confirmed that anode-make and anode-break excitation occurred, the latter becoming evident at pulse durations as brief as .3-.4 msec. The results provide quantitative characterization of cathodal and anodal strength-duration properties of the neural substrate for BSR and are discussed in terms of their value in guiding electrophysiological investigation of that substrate.", "contents": "Neural substrate for brain stimulation reward in the rat: cathodal and anodal strength-duration properties. The trade-off between current strength and duration of a stimulating pulse was studied for the rewarding and priming effects of brain stimulation reward (BSR). With cathodal pulses, strenght-duration functions for BSR had chronaxies of .8-3 msec. No differences were observed between the results for rewarding and priming effects. With anodal pulses. strength-duration curves were parallel to the cathodal curves at pulse durations of .1-5 msec, but at pulse durations greater than 5 msec the anodal curves showed a greater drop in required current intensity than did the cathodal curves. The parallel portion of the anodal curves was interpreted as due to anode-make excitation, and the drop at longer pulse durations was interpreted as due to anode-break excitation. Cathodal strength-duration functions for the motor effect elicited through the BSR electrodes had chronaxies of .15-.48 msec. Measurements of the latency of the muscle twitch confirmed that anode-make and anode-break excitation occurred, the latter becoming evident at pulse durations as brief as .3-.4 msec. The results provide quantitative characterization of cathodal and anodal strength-duration properties of the neural substrate for BSR and are discussed in terms of their value in guiding electrophysiological investigation of that substrate."}
{"id": "PMID:197131", "title": "Effects of polyphosphates on the solubility and mineralization of HA: relevance to a rationale for anticaries activity.", "content": "Preexposure of hydroxyapatite (HA) to polyphosphate reduced the near-equilibrium acid solubility of HA, the mineralization of HA, and the exchange of PO4 between medium and HA. Appreciably longer exposure times were required for maximal effects of trimetaphosphate (TMP) than of pyrophosphate (PP), tripolyphosphate (TPP), and hexametaphosphate (HMP). Calcifying solution solubilized small amounts of the HA-bound polyphosphates. This occurred to the smallest extent in the case of TMP, a fact which could have relevance for the superior anticaries effect of TMP.", "contents": "Effects of polyphosphates on the solubility and mineralization of HA: relevance to a rationale for anticaries activity. Preexposure of hydroxyapatite (HA) to polyphosphate reduced the near-equilibrium acid solubility of HA, the mineralization of HA, and the exchange of PO4 between medium and HA. Appreciably longer exposure times were required for maximal effects of trimetaphosphate (TMP) than of pyrophosphate (PP), tripolyphosphate (TPP), and hexametaphosphate (HMP). Calcifying solution solubilized small amounts of the HA-bound polyphosphates. This occurred to the smallest extent in the case of TMP, a fact which could have relevance for the superior anticaries effect of TMP."}
{"id": "PMID:197132", "title": "Activity of arginine aminopeptidases and phosphatases in inflamed palatal mucosa in denture stomatitis: a histochemical and biochemical study.", "content": "Aminopeptidase and phosphatase activity of denture stomatitis mucosa was studied histochemically and biochemically. Stomatitis clearly increased the activity of these enzymes. An enzyme resembling the chloride-activated aminopeptidase B, usually involved in inflammatory processes, was recognized in the inflamed tissue in higher concentrations than in the control tissue.", "contents": "Activity of arginine aminopeptidases and phosphatases in inflamed palatal mucosa in denture stomatitis: a histochemical and biochemical study. Aminopeptidase and phosphatase activity of denture stomatitis mucosa was studied histochemically and biochemically. Stomatitis clearly increased the activity of these enzymes. An enzyme resembling the chloride-activated aminopeptidase B, usually involved in inflammatory processes, was recognized in the inflamed tissue in higher concentrations than in the control tissue."}
{"id": "PMID:197133", "title": "Tc-99m methylene diphosphonate versus Tc-99m pyrophosphate: biologic and clinical comparison.", "content": "The biologic and imaging characteristics of Tc-99m MDP and Tc-99m PPi were compared in animals and patients using freeze-dried bone-imaging kits. Biodistribution data in rabbits showed Tc-99m MDP had slightly higher bone uptake, significantly lower blood levels, and faster urinary excretion compared with Tc-99m PPi. Duplicate studies performed on ten patients showed the following: (a) blood clearance of Tc-99m MDP was more prompt and complete, resulting in significantly lower blood levels at 4 hr; (b) urinary excretion was greater with Tc-99m MDP than with Tc-99m PPi; and (c) Tc-99m PPi showed significant red-cell labeling, whereas Tc-99m MDP did not. Image quality was generally better with Tc-99m MDP than with Tc-99 m PPi, although there was no obvious difference in diagnostic sensitivity between the two agents.", "contents": "Tc-99m methylene diphosphonate versus Tc-99m pyrophosphate: biologic and clinical comparison. The biologic and imaging characteristics of Tc-99m MDP and Tc-99m PPi were compared in animals and patients using freeze-dried bone-imaging kits. Biodistribution data in rabbits showed Tc-99m MDP had slightly higher bone uptake, significantly lower blood levels, and faster urinary excretion compared with Tc-99m PPi. Duplicate studies performed on ten patients showed the following: (a) blood clearance of Tc-99m MDP was more prompt and complete, resulting in significantly lower blood levels at 4 hr; (b) urinary excretion was greater with Tc-99m MDP than with Tc-99m PPi; and (c) Tc-99m PPi showed significant red-cell labeling, whereas Tc-99m MDP did not. Image quality was generally better with Tc-99m MDP than with Tc-99 m PPi, although there was no obvious difference in diagnostic sensitivity between the two agents."}
{"id": "PMID:197134", "title": "A comparison of technetium etidronate and pyrophosphate for acute myocardial infarct imaging.", "content": "Etidronate and pyrophosphate, labeled with Tc-95m and Tc-99m, were studied in experimentally infarcted mongrel dogs. A distribution study was conducted 2 hr after simultaneous administration of both agents in two groups of dogs. In one group, the injection was made 15 min after release of a 2-hr coronary arterial ligation. Another group was injected 48 hr after release of the ligation. The uptakes for each radiopharmaceutical and the ratio of uptakes for each sample were computed. The data show pyrophosphate to be a superior agent for the imaging of acute myocardial infarcts because of the higher uptake by infarcted myocardium and the greater contrast between infarcted myocardium and neighboring organs.", "contents": "A comparison of technetium etidronate and pyrophosphate for acute myocardial infarct imaging. Etidronate and pyrophosphate, labeled with Tc-95m and Tc-99m, were studied in experimentally infarcted mongrel dogs. A distribution study was conducted 2 hr after simultaneous administration of both agents in two groups of dogs. In one group, the injection was made 15 min after release of a 2-hr coronary arterial ligation. Another group was injected 48 hr after release of the ligation. The uptakes for each radiopharmaceutical and the ratio of uptakes for each sample were computed. The data show pyrophosphate to be a superior agent for the imaging of acute myocardial infarcts because of the higher uptake by infarcted myocardium and the greater contrast between infarcted myocardium and neighboring organs."}
{"id": "PMID:197136", "title": "Correlation of exposure to various respiratory pathogens with farmer's lung disease.", "content": "Complement-fixing antibodies (CFA) to a panel of microorganisms commonly associated with respiratory disease were measured in a number of agricultural populations. The panel included Mycoplasma pneumoniae, influenza viruses A and B, parainfluenza virus types 1, 2, and 3, adenovirus, and respiratory syncytial virus. The agricultural populations were grouped according to a clinical history of farmer's lung disease (FLD) and the presence of antibodies to the thermophilic actinomycetes (TA). Farmers with precipitating antibody activity to one or more of the TA (groups I and II) demonstrated a greater frequency of CFA to M. pneumoniae and parainfluenza virus types 1, 2, and 3 than those groups without antibody to the TA, but the level of CFA was not higher in the positive subjects. Immunoglobulin levels were also elevated in groups I and II when compared to the control groups. Unlike IgG and IgM, IgA was elevated only in the farmers who had a clinical history of FLD (group I) but not in farmers without a clinical history. The results suggest that farmers who develop FLD are exposed to a wider variety of pathogens than are other farmers, but do not respond in an accelerated manner.", "contents": "Correlation of exposure to various respiratory pathogens with farmer's lung disease. Complement-fixing antibodies (CFA) to a panel of microorganisms commonly associated with respiratory disease were measured in a number of agricultural populations. The panel included Mycoplasma pneumoniae, influenza viruses A and B, parainfluenza virus types 1, 2, and 3, adenovirus, and respiratory syncytial virus. The agricultural populations were grouped according to a clinical history of farmer's lung disease (FLD) and the presence of antibodies to the thermophilic actinomycetes (TA). Farmers with precipitating antibody activity to one or more of the TA (groups I and II) demonstrated a greater frequency of CFA to M. pneumoniae and parainfluenza virus types 1, 2, and 3 than those groups without antibody to the TA, but the level of CFA was not higher in the positive subjects. Immunoglobulin levels were also elevated in groups I and II when compared to the control groups. Unlike IgG and IgM, IgA was elevated only in the farmers who had a clinical history of FLD (group I) but not in farmers without a clinical history. The results suggest that farmers who develop FLD are exposed to a wider variety of pathogens than are other farmers, but do not respond in an accelerated manner."}
{"id": "PMID:197147", "title": "Glomus tumor of the digits.", "content": "Eight cases of glomus tumor of the digits seen during an 8-year period are reviewed. This number comprised 1.2% of all hand tumors encountered. Symptoms of cold intolerance and exquisite tenderness were common to all. The average duration of symptoms prior to diagnosis and treatment was 7 years. Five patients gave a history of either frostbite (two) or trauma (three) prior to onset of symptoms. The tumor was subungual in six of the eight patients, with a relatively even distribution among all digits. Roentgenographic changes of erosion of the distal phalanx were present in 50% of the tumors. Surgical excision was curative in all instances.", "contents": "Glomus tumor of the digits. Eight cases of glomus tumor of the digits seen during an 8-year period are reviewed. This number comprised 1.2% of all hand tumors encountered. Symptoms of cold intolerance and exquisite tenderness were common to all. The average duration of symptoms prior to diagnosis and treatment was 7 years. Five patients gave a history of either frostbite (two) or trauma (three) prior to onset of symptoms. The tumor was subungual in six of the eight patients, with a relatively even distribution among all digits. Roentgenographic changes of erosion of the distal phalanx were present in 50% of the tumors. Surgical excision was curative in all instances."}
{"id": "PMID:197148", "title": "Nerve tumors of the hand and forearm.", "content": "Peripheral nerve tumors comprise less than 5% of all tumors of the hand. The most common solitary nerve tumor is the neurilemmoma, which arises from the neural sheath, is well encapsulated, minimally symptomatic, and may be surgically enucleated without producing a neurological deficit. Neurofibromas may be solitary, multiple, or associated with von Recklinghausen's disease. They are usually centrally placed with nerve fibers traversing the tumor mass making it more difficult to remove the tumor without producing permanent neurological damage. Malignant tumors include neurofibrosarcomas which often are very aggressive, requiring wide excision or amputation, and the rare neuroepitheliomas. Reported nerve tumors, intraneural in location but nonneural in origin, include fibrofatty infiltration of the median and digital nerves, intraneural lipoma, hemangioma, and ganglion cysts. These lesions may be treated by decompression or excision, depending on the nature of the tumor. Four unusual cases are described.", "contents": "Nerve tumors of the hand and forearm. Peripheral nerve tumors comprise less than 5% of all tumors of the hand. The most common solitary nerve tumor is the neurilemmoma, which arises from the neural sheath, is well encapsulated, minimally symptomatic, and may be surgically enucleated without producing a neurological deficit. Neurofibromas may be solitary, multiple, or associated with von Recklinghausen's disease. They are usually centrally placed with nerve fibers traversing the tumor mass making it more difficult to remove the tumor without producing permanent neurological damage. Malignant tumors include neurofibrosarcomas which often are very aggressive, requiring wide excision or amputation, and the rare neuroepitheliomas. Reported nerve tumors, intraneural in location but nonneural in origin, include fibrofatty infiltration of the median and digital nerves, intraneural lipoma, hemangioma, and ganglion cysts. These lesions may be treated by decompression or excision, depending on the nature of the tumor. Four unusual cases are described."}
{"id": "PMID:197149", "title": "Malignant fibrous histiocytoma of the forearm: report of a case and review of the literature.", "content": "The tissue histiocyte can give rise to a variety of lesions, either benign or malignant, and the latter often is confused with other sarcomas. The multipotential nature of the histiocyte results in the presence of at least five different cell types in these tumors, and all may be derived from a common precursor cell. The anaplasia of elements which differentiate as fibroblasts appears to correlate with survival. The tumors may be highly malignant, and the 10 year survival rate approximates 40%. Aggressive surgical management of these tumors is mandatory, with either wide en bloc resection or primary amputation of the involved extremity. Should the tumor recur locally after a wide resection and there be no detectable metastases, prompt amputation is indicated.", "contents": "Malignant fibrous histiocytoma of the forearm: report of a case and review of the literature. The tissue histiocyte can give rise to a variety of lesions, either benign or malignant, and the latter often is confused with other sarcomas. The multipotential nature of the histiocyte results in the presence of at least five different cell types in these tumors, and all may be derived from a common precursor cell. The anaplasia of elements which differentiate as fibroblasts appears to correlate with survival. The tumors may be highly malignant, and the 10 year survival rate approximates 40%. Aggressive surgical management of these tumors is mandatory, with either wide en bloc resection or primary amputation of the involved extremity. Should the tumor recur locally after a wide resection and there be no detectable metastases, prompt amputation is indicated."}
{"id": "PMID:197162", "title": "The dissociation of transplantable tumors.", "content": "Four animal transplantable solid tumors, composed of varying morphologic architecture and intercellular specializations, were studied by light and electron microscopy. These tumors were dissociated into viable single cell populations using a combination of mechanical and enzymatic methods. The conditions necessary for optimal dissociation consisted of (a) preparation of the tumor to maximize the tissue surface area, (b) enzymatic digestion with continuous agitation and (c) additional agitation to release loosely attached cells. Other factors that influenced the dissociation were optimized and discussed.", "contents": "The dissociation of transplantable tumors. Four animal transplantable solid tumors, composed of varying morphologic architecture and intercellular specializations, were studied by light and electron microscopy. These tumors were dissociated into viable single cell populations using a combination of mechanical and enzymatic methods. The conditions necessary for optimal dissociation consisted of (a) preparation of the tumor to maximize the tissue surface area, (b) enzymatic digestion with continuous agitation and (c) additional agitation to release loosely attached cells. Other factors that influenced the dissociation were optimized and discussed."}
{"id": "PMID:197163", "title": "Laser cytophotometric detection of variations in spatial distribution of concanavalin-A cell surface receptors following viral infection.", "content": "Human cells in culture (H.Ep. 2) were infected with herpes simplex virus type 2 at a multiplicity of infection (m.o.i.) of 3 for 3, 18 and 36 hr. Spatial redistribution of concanavalin (Con-A) cell surface receptor sites was detected by an indirect double-antibody (peroxidase-conjugated goat anti-rabbit to rabbit anti-Con-A) immunoenzymatic staining reaction which rendered the Con-A sites visible to light microscopy and to flow laser cytophotometry. Significant spatial redistribution of cell surface Con-A receptor sites occurred within the first 3 hr after infection with herpes simplex virus type 2. The infected cells must be in the presence of Con-A for the redistribution to occur, and significant redistribution occurs only at 37 degrees C. Fixation of infected cells prior to application of Con-A prevented this spatial redistribution of Con-A receptor sites.", "contents": "Laser cytophotometric detection of variations in spatial distribution of concanavalin-A cell surface receptors following viral infection. Human cells in culture (H.Ep. 2) were infected with herpes simplex virus type 2 at a multiplicity of infection (m.o.i.) of 3 for 3, 18 and 36 hr. Spatial redistribution of concanavalin (Con-A) cell surface receptor sites was detected by an indirect double-antibody (peroxidase-conjugated goat anti-rabbit to rabbit anti-Con-A) immunoenzymatic staining reaction which rendered the Con-A sites visible to light microscopy and to flow laser cytophotometry. Significant spatial redistribution of cell surface Con-A receptor sites occurred within the first 3 hr after infection with herpes simplex virus type 2. The infected cells must be in the presence of Con-A for the redistribution to occur, and significant redistribution occurs only at 37 degrees C. Fixation of infected cells prior to application of Con-A prevented this spatial redistribution of Con-A receptor sites."}
{"id": "PMID:197164", "title": "[Action of cyclic N6-monobutyryladenosine-3':5'-monophosphate (mb-cAMP) on cell on cell and explant cultures of the PNS and CNS in vitro].", "content": "Chick embryo trigeminal ganglia of nine days and hippocampus excised from fetal rats between the sixteenth and eighteenth day of gestation were cultivated in cell- and explantcultures in Maximow-chambers. The cultures were placed in a medium containing 2 mM, 1 mM, 0.2 mM or 0.02 mM cyclic N6-Monobutyryladenosin-3':5'-monophosphat (mb-cAMP). The cultures of the PNS, the trigeminal ganglai show after 48 h by 1 mM mb-cAMP longer nerve fibers and a increased nerve fiber index. Smaller concentration did not change significant nerve fiber growth. Cell- and explantcultures of the hippocampus show a stimulation of the nerve fiber growth and the nerve fiberindex by concentration of 0.02 mM mb-cAMP. After ten days in vitro the nerve cells degenerated by higher concentrations.", "contents": "[Action of cyclic N6-monobutyryladenosine-3':5'-monophosphate (mb-cAMP) on cell on cell and explant cultures of the PNS and CNS in vitro]. Chick embryo trigeminal ganglia of nine days and hippocampus excised from fetal rats between the sixteenth and eighteenth day of gestation were cultivated in cell- and explantcultures in Maximow-chambers. The cultures were placed in a medium containing 2 mM, 1 mM, 0.2 mM or 0.02 mM cyclic N6-Monobutyryladenosin-3':5'-monophosphat (mb-cAMP). The cultures of the PNS, the trigeminal ganglai show after 48 h by 1 mM mb-cAMP longer nerve fibers and a increased nerve fiber index. Smaller concentration did not change significant nerve fiber growth. Cell- and explantcultures of the hippocampus show a stimulation of the nerve fiber growth and the nerve fiberindex by concentration of 0.02 mM mb-cAMP. After ten days in vitro the nerve cells degenerated by higher concentrations."}
{"id": "PMID:197165", "title": "Appearanc of cytotoxic cells within the bronchus after local infection with herpes simplex virus.", "content": "Cells from rabbit spleens, bronchial washings (BW) and bronchus-associated lymphoid tissues (BALT) were examined for their ability to lyse cells infected with herpes simplex virus (HSV). Specific lysis of HSV-infected cells was mediated by BW cells as early as 4 days after intratracheal infection of the rabbits with the virus whereas lysis by spleen cells and BALT cells was not detected until 7 or more days after infection. Lysis by spleen cells was initially detected 7 days after intraperitoneal injection of the virus but lysis by BW and BALT cells was not observed until 14 days after infection. Although spleen, BW, and BALT cells could lyse antibody-coated target cells, antibodies detectable by antibody-dependent cellular cytotoxicity could not be detected in bronchial washings until 7 or more days after infection. The data suggest that cells capable of direct cytotoxicity of virus-infected cells appear within the bronchus after local infection by the virus.", "contents": "Appearanc of cytotoxic cells within the bronchus after local infection with herpes simplex virus. Cells from rabbit spleens, bronchial washings (BW) and bronchus-associated lymphoid tissues (BALT) were examined for their ability to lyse cells infected with herpes simplex virus (HSV). Specific lysis of HSV-infected cells was mediated by BW cells as early as 4 days after intratracheal infection of the rabbits with the virus whereas lysis by spleen cells and BALT cells was not detected until 7 or more days after infection. Lysis by spleen cells was initially detected 7 days after intraperitoneal injection of the virus but lysis by BW and BALT cells was not observed until 14 days after infection. Although spleen, BW, and BALT cells could lyse antibody-coated target cells, antibodies detectable by antibody-dependent cellular cytotoxicity could not be detected in bronchial washings until 7 or more days after infection. The data suggest that cells capable of direct cytotoxicity of virus-infected cells appear within the bronchus after local infection by the virus."}
{"id": "PMID:197166", "title": "Thymosin-induced human serum factor increasing cyclic AMP.", "content": "Thymosin has virtually no in vitro effect on cyclic AMP levels in thymocytes and seems not to react with either the beta-adrenergic receptor or with the putative human serum thymic factor (SF) receptor. However, when thymosin is injected into patients lacking SF activity, it induces the appearance of a serum factor which increases cellular cyclic AMP levels in thymocytes in vitro. This factor appears to act on a membrane site distinct from the beta-adrenergic receptors.", "contents": "Thymosin-induced human serum factor increasing cyclic AMP. Thymosin has virtually no in vitro effect on cyclic AMP levels in thymocytes and seems not to react with either the beta-adrenergic receptor or with the putative human serum thymic factor (SF) receptor. However, when thymosin is injected into patients lacking SF activity, it induces the appearance of a serum factor which increases cellular cyclic AMP levels in thymocytes in vitro. This factor appears to act on a membrane site distinct from the beta-adrenergic receptors."}
{"id": "PMID:197167", "title": "Macrophages are required for the dextran-sulfate induced activation of B lymphocytes.", "content": "The proliferative response induced by the B cell activating ligand dextran-sulfate (DxS) requires the presence of macrophage-produced factors or the macrophage-substituting compound 2-mercaptoethanol. Thus, the mechanism for activation of mouse B splenic lymphocytes is different for DxS than for other polyclonal B cell activators such as lipopolysaccharides, which can trigger B cells directely in the absence of the helper factors. It is suggested that the disappearance of the DxS-induced response could be studied in a simple functional tests for the efficiency of macrophage depletion obtained by different techniques.", "contents": "Macrophages are required for the dextran-sulfate induced activation of B lymphocytes. The proliferative response induced by the B cell activating ligand dextran-sulfate (DxS) requires the presence of macrophage-produced factors or the macrophage-substituting compound 2-mercaptoethanol. Thus, the mechanism for activation of mouse B splenic lymphocytes is different for DxS than for other polyclonal B cell activators such as lipopolysaccharides, which can trigger B cells directely in the absence of the helper factors. It is suggested that the disappearance of the DxS-induced response could be studied in a simple functional tests for the efficiency of macrophage depletion obtained by different techniques."}
{"id": "PMID:197168", "title": "Antibody response to simian virus 40 tumor antigen in nude mice reconstituted with T cells.", "content": "Athymic BALB/c nude mice (nu/nu) fail to generate circulating antibodies to simian virus 40 (SV40) tumor (T) antigen when immunized with SV40-transformed mouse cells or with T antigen positive somatic cell hybrids derived from SV40-transformed human and normal mouse parental cells. However, normal BALB/c mice readily produce antibodies to SV40 T antigen. When nude mice were reconstituted with normal syngeneic T lymphocytes from spleen or thymus source, the humoral immune responsiveness to SV40 T antigen was restored.", "contents": "Antibody response to simian virus 40 tumor antigen in nude mice reconstituted with T cells. Athymic BALB/c nude mice (nu/nu) fail to generate circulating antibodies to simian virus 40 (SV40) tumor (T) antigen when immunized with SV40-transformed mouse cells or with T antigen positive somatic cell hybrids derived from SV40-transformed human and normal mouse parental cells. However, normal BALB/c mice readily produce antibodies to SV40 T antigen. When nude mice were reconstituted with normal syngeneic T lymphocytes from spleen or thymus source, the humoral immune responsiveness to SV40 T antigen was restored."}
{"id": "PMID:197169", "title": "Antibodies to bacterial and tumor-derived antigens in sera from normal guinea pigs.", "content": "Antibodies that react with radiolabeled antigens derived from guinea pig line-10 tumor cells and Mycobacterium bovis (BCG) were detected in sera from normal tumor-free strain-2 guinea pigs (NGPS). Binding by NGPS to the two antigens was inhibited by extracts of either line-10 cells or BCG. Binding by NGPS to the line-10 antigen was inhibited by a number of other bacterial extracts. NGPS was tested after absorption with a variety of cells including line-10, line-1, normal guinea pig spleen, normal adult and fetal liver cells. Results indicated that some of the antibodies in NGPS were directed to line-10-specific determinants. The specific stimulating antigen for these antibodies was not identified but because of the antigenic relationship between BCG, line-10 cells and other bacteria, antibodies to line-10-associated antigens might have been induced by exposure to environmental microorganisms.", "contents": "Antibodies to bacterial and tumor-derived antigens in sera from normal guinea pigs. Antibodies that react with radiolabeled antigens derived from guinea pig line-10 tumor cells and Mycobacterium bovis (BCG) were detected in sera from normal tumor-free strain-2 guinea pigs (NGPS). Binding by NGPS to the two antigens was inhibited by extracts of either line-10 cells or BCG. Binding by NGPS to the line-10 antigen was inhibited by a number of other bacterial extracts. NGPS was tested after absorption with a variety of cells including line-10, line-1, normal guinea pig spleen, normal adult and fetal liver cells. Results indicated that some of the antibodies in NGPS were directed to line-10-specific determinants. The specific stimulating antigen for these antibodies was not identified but because of the antigenic relationship between BCG, line-10 cells and other bacteria, antibodies to line-10-associated antigens might have been induced by exposure to environmental microorganisms."}
{"id": "PMID:197172", "title": "High densitiy lipoprotein (HDL) polymorphisms in rabbit: production of antibody to rabbit allotype (R 67) in sheep.", "content": "Antiserum to a rabbit HDL allotype has been produced in a sheep. Qualitative and quantitative immunological test of whole rabbit serum and purified HDL polypeptides, as well as association tests, showed that the absorbed sheep immune serum reacts with the HDL allotype referred to as R 67.", "contents": "High densitiy lipoprotein (HDL) polymorphisms in rabbit: production of antibody to rabbit allotype (R 67) in sheep. Antiserum to a rabbit HDL allotype has been produced in a sheep. Qualitative and quantitative immunological test of whole rabbit serum and purified HDL polypeptides, as well as association tests, showed that the absorbed sheep immune serum reacts with the HDL allotype referred to as R 67."}
{"id": "PMID:197173", "title": "Mechanisms of disease and immunity in cholera: a review.", "content": "The adenyl cyclase-activating enterotoxin of Vibrio cholerae was shown to contain two types of subunit: six smaller units (L) that are responsible for the binding to cell membrane receptors and a larger unit (H) that mediates the toxic action. The receptor was identified as the ganglioside GM1 (galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide), and the results suggested that penetration of the toxin molecule into the membrane follows the rapid binding to GM1. The relationship of these findings to the mechanism of protective immunity, which is mediated by antibodies to the enterotoxin as well as those to the cell wall lipopolysaccharide of V. cholerae, was investigated. The antitoxic antibodies were directed mainly against the L subunit and protected by preventing binding of toxin; the antibacterial antibodies probably interfered with adhesion of V. cholerae to the intestine. The finding that the immune responses to toxin and bacteria act synergistically in protection against experimental cholera indicates that an improved cholera vaccine should contain both toxoid and lipopolysaccharide as antigens. In the rabbit, either subcutaneous or enteral immunization gave rise to intestinal synthesis of specific antibodies to V. cholerae.", "contents": "Mechanisms of disease and immunity in cholera: a review. The adenyl cyclase-activating enterotoxin of Vibrio cholerae was shown to contain two types of subunit: six smaller units (L) that are responsible for the binding to cell membrane receptors and a larger unit (H) that mediates the toxic action. The receptor was identified as the ganglioside GM1 (galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide), and the results suggested that penetration of the toxin molecule into the membrane follows the rapid binding to GM1. The relationship of these findings to the mechanism of protective immunity, which is mediated by antibodies to the enterotoxin as well as those to the cell wall lipopolysaccharide of V. cholerae, was investigated. The antitoxic antibodies were directed mainly against the L subunit and protected by preventing binding of toxin; the antibacterial antibodies probably interfered with adhesion of V. cholerae to the intestine. The finding that the immune responses to toxin and bacteria act synergistically in protection against experimental cholera indicates that an improved cholera vaccine should contain both toxoid and lipopolysaccharide as antigens. In the rabbit, either subcutaneous or enteral immunization gave rise to intestinal synthesis of specific antibodies to V. cholerae."}
{"id": "PMID:197174", "title": "Pathogenesis of infection with Bordetella pertussis in hamster tracheal organ culture.", "content": "Hamster tracheal organ culture was employed as a model for study of the pathogenesis of infection due to Bordetella pertussis. Infected tracheal explants were examined with light, immunofluorescence, and electrom microscopy. B. pertussis organisms preferentially attached to the ciliated cells, producing ciliostasis and marked destruction of the subcellular organelles followed by expulsion of these cells from the epithelial layer. Other nonciliated respiratory epithelial cells appeared to be unaffected. Metabolic studies on infected tracheal cultrues indicated that significant deficiencies in syntheiss of host cell protein accompanied early cytopathology. Similarities and differences in host cell and parasite interaction were noted between B. pertussis and other pathogenic agents studied in this system.", "contents": "Pathogenesis of infection with Bordetella pertussis in hamster tracheal organ culture. Hamster tracheal organ culture was employed as a model for study of the pathogenesis of infection due to Bordetella pertussis. Infected tracheal explants were examined with light, immunofluorescence, and electrom microscopy. B. pertussis organisms preferentially attached to the ciliated cells, producing ciliostasis and marked destruction of the subcellular organelles followed by expulsion of these cells from the epithelial layer. Other nonciliated respiratory epithelial cells appeared to be unaffected. Metabolic studies on infected tracheal cultrues indicated that significant deficiencies in syntheiss of host cell protein accompanied early cytopathology. Similarities and differences in host cell and parasite interaction were noted between B. pertussis and other pathogenic agents studied in this system."}
{"id": "PMID:197175", "title": "Lymphocytosis-promoting factor of Bordetella pertussis: isolation, characterization, and biological activity.", "content": "The leukocytosis and lymphocytosis-promoting factor (LPF) of Bordetella pertussis has been isolated in apparently pure form. LPF is a protein essentially free of lipid and carbohydrate with an estimated molecular weight of 67,000-73,600 daltons. Purified LPF induced both histamine sensitization and refractoriness to epinephrine-induced hyperglycemia and was a murine thymus-derived (T-) cell mitogen. Adenyl cyclase activity also appeared to be associated with LPF.", "contents": "Lymphocytosis-promoting factor of Bordetella pertussis: isolation, characterization, and biological activity. The leukocytosis and lymphocytosis-promoting factor (LPF) of Bordetella pertussis has been isolated in apparently pure form. LPF is a protein essentially free of lipid and carbohydrate with an estimated molecular weight of 67,000-73,600 daltons. Purified LPF induced both histamine sensitization and refractoriness to epinephrine-induced hyperglycemia and was a murine thymus-derived (T-) cell mitogen. Adenyl cyclase activity also appeared to be associated with LPF."}
{"id": "PMID:197178", "title": "Bilateral chemodectoma in the neck.", "content": "A 55-year-old man with bilateral cervical chemodectoma is reported. The differences between tumours of the carotid body and those of the glomus intravagale are described and a brief review of the investigation and management of such tumours is given.", "contents": "Bilateral chemodectoma in the neck. A 55-year-old man with bilateral cervical chemodectoma is reported. The differences between tumours of the carotid body and those of the glomus intravagale are described and a brief review of the investigation and management of such tumours is given."}
{"id": "PMID:197181", "title": "An electron spin resonance study of cholestane spin label in aqueous mixtures of biliary lipids.", "content": "The effect of cholesterol on the fluidity of the phospholipid matrix in mixed micelles derived from bile salts and lecithin has been determined by the paramagnetic probe technique. It was found that correlation times for the cholestane spin label were discontinuous functions of cholesterol content and that these discontinuities correlate with the equilibrium solubility limit for cholesterol in this quaternary system. The origin of these discontinuities is attributed to the existence of another aggregate in addition to the discshaped mixed micelle in lipid solutions supersaturated with cholesterol.", "contents": "An electron spin resonance study of cholestane spin label in aqueous mixtures of biliary lipids. The effect of cholesterol on the fluidity of the phospholipid matrix in mixed micelles derived from bile salts and lecithin has been determined by the paramagnetic probe technique. It was found that correlation times for the cholestane spin label were discontinuous functions of cholesterol content and that these discontinuities correlate with the equilibrium solubility limit for cholesterol in this quaternary system. The origin of these discontinuities is attributed to the existence of another aggregate in addition to the discshaped mixed micelle in lipid solutions supersaturated with cholesterol."}
{"id": "PMID:197182", "title": "Differential characteristics of purified hepatic triglyceride lipase and lipoprotein lipase from human postheparin plasma.", "content": "Evidence is presented that hepatic triglyceride lipase (H-TGL) and lipoprotein lipase (LPL), purified from human postheparin plasma, can each hydrolyze both glyceryl trioleate and palmitoyl-CoA. The average ratio of glyceryl trioleate/palmitoyl-CoA hydrolase activities, obtained with enzyme preparations from 15 human postheparin plasma samples was 1.30 (1.18-1.52) for H-TGL and 8.75 (7.45-10.25) for LPL. Albumin was identified as the serum cofactor required for the hydrolysis of palmitoyl-CoA by H-TGL. It protected this enzyme from inactivation by this substrate. In contrast, palmitoyl-CoA activated and protected LPL from denaturation by dilution and incubation at 25 degrees C. The effects of other detergents were investigated on glyceryl trioleate hydrolase activities of both enzymes. Sodium dodecyl sulfate (0.4 mM) and Trisoleate (0.4 mM), which also effectively activated and protected LPL against inactivation, had only moderate protective effect on H-TGL. Sodium dodecyl sulfate at a higher concentration (1 mM) produced little or no inhibition of LPL, while completely inactivating H-TGL. Conversely, sodium taurodeoxycholate (0.4 mM) protected and activated H-TGL, but had only moderate protective effect on LPL. Triton X-100 (0.1-0.8 mM) and egg lysolecithin (0.05-2 mM) also protected H-TGL, but not LPL. The very dissimilar effects of detergents on preparations on H-TGL and LPL may form the basis for the direct assay of each enzyme in the presence of the other.", "contents": "Differential characteristics of purified hepatic triglyceride lipase and lipoprotein lipase from human postheparin plasma. Evidence is presented that hepatic triglyceride lipase (H-TGL) and lipoprotein lipase (LPL), purified from human postheparin plasma, can each hydrolyze both glyceryl trioleate and palmitoyl-CoA. The average ratio of glyceryl trioleate/palmitoyl-CoA hydrolase activities, obtained with enzyme preparations from 15 human postheparin plasma samples was 1.30 (1.18-1.52) for H-TGL and 8.75 (7.45-10.25) for LPL. Albumin was identified as the serum cofactor required for the hydrolysis of palmitoyl-CoA by H-TGL. It protected this enzyme from inactivation by this substrate. In contrast, palmitoyl-CoA activated and protected LPL from denaturation by dilution and incubation at 25 degrees C. The effects of other detergents were investigated on glyceryl trioleate hydrolase activities of both enzymes. Sodium dodecyl sulfate (0.4 mM) and Trisoleate (0.4 mM), which also effectively activated and protected LPL against inactivation, had only moderate protective effect on H-TGL. Sodium dodecyl sulfate at a higher concentration (1 mM) produced little or no inhibition of LPL, while completely inactivating H-TGL. Conversely, sodium taurodeoxycholate (0.4 mM) protected and activated H-TGL, but had only moderate protective effect on LPL. Triton X-100 (0.1-0.8 mM) and egg lysolecithin (0.05-2 mM) also protected H-TGL, but not LPL. The very dissimilar effects of detergents on preparations on H-TGL and LPL may form the basis for the direct assay of each enzyme in the presence of the other."}
{"id": "PMID:197183", "title": "Binding, internalization, and degradation of high density lipoprotein by cultured normal human fibroblasts.", "content": "Comparative studies were made of the metabolism of plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) by cultured normal human fibroblasts. On a molar basis, the surface binding of (125)I-HDL was only slightly less than that of (125)I-LDL, whereas the rates of internalization and degradation of (125)I-HDL were very low relative to those of (125)I-LDL. The relationships of internalization and degradation to binding suggested the presence of a saturable uptake mechanism for LDL functionally related to high-affinity binding. This was confirmed by the finding that the total uptake of (125)I-LDL (internalized plus degraded) at 5 micro g LDL protein/ml was 100-fold greater than that attributable to fluid or bulk pinocytosis, quantified with [(14)C]sucrose, and 10-fold greater than that attributable to the sum of fluid endocytosis and adsorptive endocytosis. In contrast, (125)I-HDL uptake could be almost completely accounted for by the uptake of medium during pinocytosis and by invagination of surface membrane (bearing bound lipoprotein) during pinocytosis. These findings imply that, at most, only a small fraction of bound HDL binds to the high-affinity LDL receptor and/or that HDL binding there is internalized very slowly. The rate of (125)I-HDL degradation by cultured fibroblasts (per unit cell mass) exceeded an estimate of the turnover rate of HDL in vivo, suggesting that peripheral tissues may contribute to HDL catabolism. In accordance with their differing rates of uptake and cholesterol content, LDL increased the cholesterol content of fibroblasts and selectively inhibited sterol biosynthesis, whereas HDL had neither effect.", "contents": "Binding, internalization, and degradation of high density lipoprotein by cultured normal human fibroblasts. Comparative studies were made of the metabolism of plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) by cultured normal human fibroblasts. On a molar basis, the surface binding of (125)I-HDL was only slightly less than that of (125)I-LDL, whereas the rates of internalization and degradation of (125)I-HDL were very low relative to those of (125)I-LDL. The relationships of internalization and degradation to binding suggested the presence of a saturable uptake mechanism for LDL functionally related to high-affinity binding. This was confirmed by the finding that the total uptake of (125)I-LDL (internalized plus degraded) at 5 micro g LDL protein/ml was 100-fold greater than that attributable to fluid or bulk pinocytosis, quantified with [(14)C]sucrose, and 10-fold greater than that attributable to the sum of fluid endocytosis and adsorptive endocytosis. In contrast, (125)I-HDL uptake could be almost completely accounted for by the uptake of medium during pinocytosis and by invagination of surface membrane (bearing bound lipoprotein) during pinocytosis. These findings imply that, at most, only a small fraction of bound HDL binds to the high-affinity LDL receptor and/or that HDL binding there is internalized very slowly. The rate of (125)I-HDL degradation by cultured fibroblasts (per unit cell mass) exceeded an estimate of the turnover rate of HDL in vivo, suggesting that peripheral tissues may contribute to HDL catabolism. In accordance with their differing rates of uptake and cholesterol content, LDL increased the cholesterol content of fibroblasts and selectively inhibited sterol biosynthesis, whereas HDL had neither effect."}
{"id": "PMID:197184", "title": "A comparative study of surface binding of human low density and high density lipoproteins to human fibroblasts: regulation by sterols and susceptibility to proteolytic digestion.", "content": "Binding of 125I-low density lipoprotein (LDL) and 125I-high density lipoprotein (HDL) was determined in cultured human fibroblasts from a normal subject and two subjects with homozygous familial hypercholesterolemia (HFH). Binding was assayed at 0 degree C to minimize the internalization of labeled lipoproteins. The binding of LDL and of HDL were compared following interventions reported to affect LDL binding in normal fibroblast. LDL binding to normal cells increased two to three fold 24 hours after transfer from medium containing whole fetal calf serum to medium containing lipoprotein-deficient fetal calf serum. This increase was completely blocked in the presence of cycloheximide (200 microgram/ml) or 7-ketocholesterol (2.5 microgram/ml). This increased capacity of normal fibroblasts to bind LDL could be reduced 70-80% by a subsequent 18-hour incubation with cholesterol (50 microgram/ml) or 7-ketocholesterol (2.5 microgram/ml). In contrast, no significant change in HDL binding to normal fibroblasts was observed after any of these interventions. HFH cells to show any significant change in either LDL binding or HDL binding following these interventions. These results suggest that HDL binding sites on normal fibroblasts are for the most part distinct from LDL binding sites. They also support the conclusion that LDL binding sites on HFH cells are for the most part qualitatively different from those on normal cells.", "contents": "A comparative study of surface binding of human low density and high density lipoproteins to human fibroblasts: regulation by sterols and susceptibility to proteolytic digestion. Binding of 125I-low density lipoprotein (LDL) and 125I-high density lipoprotein (HDL) was determined in cultured human fibroblasts from a normal subject and two subjects with homozygous familial hypercholesterolemia (HFH). Binding was assayed at 0 degree C to minimize the internalization of labeled lipoproteins. The binding of LDL and of HDL were compared following interventions reported to affect LDL binding in normal fibroblast. LDL binding to normal cells increased two to three fold 24 hours after transfer from medium containing whole fetal calf serum to medium containing lipoprotein-deficient fetal calf serum. This increase was completely blocked in the presence of cycloheximide (200 microgram/ml) or 7-ketocholesterol (2.5 microgram/ml). This increased capacity of normal fibroblasts to bind LDL could be reduced 70-80% by a subsequent 18-hour incubation with cholesterol (50 microgram/ml) or 7-ketocholesterol (2.5 microgram/ml). In contrast, no significant change in HDL binding to normal fibroblasts was observed after any of these interventions. HFH cells to show any significant change in either LDL binding or HDL binding following these interventions. These results suggest that HDL binding sites on normal fibroblasts are for the most part distinct from LDL binding sites. They also support the conclusion that LDL binding sites on HFH cells are for the most part qualitatively different from those on normal cells."}
{"id": "PMID:197185", "title": "Secretion of the arginine-rich and A-I apolipoproteins by the isolated perfused rat liver.", "content": "Rates of secretion of the arginine-rich and A-I apolipoproteins into perfusates of rat livers were measured by specific radioimmunoassays. Livers were perfused for 6 hr in a recirculating system in the presence or absence of 5,5'-dithionitrobenzoic acid, an inhibitor of lecithin-cholesterol acyltransferase. Arginine-rich apoprotein (ARP) was secreted at a constant or increasing hourly rate of about 40 micro g/g liver, whereas the rate of accumulation of apoprotein A-I decreased progressively from about 12 to less than 5 micro g/g liver. These rates were not affected by inhibition of lecithin-cholesterol acyltransferase. The distribution of these two apolipoproteins was also measured in ultracentrifugally separated lipoprotein fractions from perfusates and blood plasma. Apoprotein A-I was mainly in high density lipoproteins, with the remainder in proteins of density > 1.21 g/ml. The percent of apoprotein A-I in the latter fraction was lowest in plasma (5%); in perfusates it was greater when the enzyme inhibitor was present (33%) than in its absence (11%). By contrast much less ARP was in proteins of d > 1.21 g/ml in perfusates than in blood plasma. Discoidal high density lipoproteins, recovered from perfusates in which lecithin-cholesterol acyltransferase was inhibited, contained much more arginine-rich apoprotein than apoprotein A-I (ratio = 10:1). The ratio in spherical plasma HDL was 1:7 and that in perfusate high density lipoproteins obtained in the absence of enzyme inhibitor was intermediate (2:1). It is concluded that: 1) the arginine-rich apoprotein is a major apolipoprotein whereas apoprotein A-I is a minor apolipoprotein secreted by the perfused rat liver; 2) the properties of the high density lipoproteins produced in this system are remarkably similar to those found in humans with genetically determined deficiency of lecithin-cholesterol acyltransferase.", "contents": "Secretion of the arginine-rich and A-I apolipoproteins by the isolated perfused rat liver. Rates of secretion of the arginine-rich and A-I apolipoproteins into perfusates of rat livers were measured by specific radioimmunoassays. Livers were perfused for 6 hr in a recirculating system in the presence or absence of 5,5'-dithionitrobenzoic acid, an inhibitor of lecithin-cholesterol acyltransferase. Arginine-rich apoprotein (ARP) was secreted at a constant or increasing hourly rate of about 40 micro g/g liver, whereas the rate of accumulation of apoprotein A-I decreased progressively from about 12 to less than 5 micro g/g liver. These rates were not affected by inhibition of lecithin-cholesterol acyltransferase. The distribution of these two apolipoproteins was also measured in ultracentrifugally separated lipoprotein fractions from perfusates and blood plasma. Apoprotein A-I was mainly in high density lipoproteins, with the remainder in proteins of density > 1.21 g/ml. The percent of apoprotein A-I in the latter fraction was lowest in plasma (5%); in perfusates it was greater when the enzyme inhibitor was present (33%) than in its absence (11%). By contrast much less ARP was in proteins of d > 1.21 g/ml in perfusates than in blood plasma. Discoidal high density lipoproteins, recovered from perfusates in which lecithin-cholesterol acyltransferase was inhibited, contained much more arginine-rich apoprotein than apoprotein A-I (ratio = 10:1). The ratio in spherical plasma HDL was 1:7 and that in perfusate high density lipoproteins obtained in the absence of enzyme inhibitor was intermediate (2:1). It is concluded that: 1) the arginine-rich apoprotein is a major apolipoprotein whereas apoprotein A-I is a minor apolipoprotein secreted by the perfused rat liver; 2) the properties of the high density lipoproteins produced in this system are remarkably similar to those found in humans with genetically determined deficiency of lecithin-cholesterol acyltransferase."}
{"id": "PMID:197186", "title": "Lipid metabolism in cultured cells. XVI. Lipoprotein binding and HMG CoA reductase levels in normal and tumor virus-transformed human fibroblasts.", "content": "The loss in feedback control of cholesterol biosynthesis in tumor cells was examined in tissue culture. Human fibroblasts from normal subjects, SV40 tumor virus-transformed cell lines, and homozygous familial hypercholesterolemic cells as reference, were grown in tissue culture. Experiments were conducted to relate the regulatory enzyme for cholesterol biosynthesis, HMG CoA reductase, and the membrane-located binding receptors for low density lipoproteins (LDL) that mediate feedback control in normal cells. Monolayers of virus-transformed tumor cells exhibited specific (125)I-labeled LDL binding of 152 +/- 21 ng/mg cell protein, which was essentially the same as that of normal fibroblasts (135 +/- 20 ng/mg). Binding of LDL by familial hypercholesterolemic cells used as controls was only 8 +/- 3 ng/mg under the same test conditions. Basal levels of HMG CoA reductase in tumor cells of 45.2 +/- 6.5 units/mg cell protein were about twice those of normal cells. However, in contrast to the lack of feedback control of this enzyme observed with tumors in vivo, in both the normal and the transformed cells in vitro, activity of the enzyme decreased about fourfold when serum lipids were added. These findings demonstrate that tumor cells growing in vitro contain a normal complement of the membrane-located binding receptors for low density lipoproteins and, although the basal levels are higher than normal, an effective feedback regulation of the enzyme HMG CoA reductase is retained.", "contents": "Lipid metabolism in cultured cells. XVI. Lipoprotein binding and HMG CoA reductase levels in normal and tumor virus-transformed human fibroblasts. The loss in feedback control of cholesterol biosynthesis in tumor cells was examined in tissue culture. Human fibroblasts from normal subjects, SV40 tumor virus-transformed cell lines, and homozygous familial hypercholesterolemic cells as reference, were grown in tissue culture. Experiments were conducted to relate the regulatory enzyme for cholesterol biosynthesis, HMG CoA reductase, and the membrane-located binding receptors for low density lipoproteins (LDL) that mediate feedback control in normal cells. Monolayers of virus-transformed tumor cells exhibited specific (125)I-labeled LDL binding of 152 +/- 21 ng/mg cell protein, which was essentially the same as that of normal fibroblasts (135 +/- 20 ng/mg). Binding of LDL by familial hypercholesterolemic cells used as controls was only 8 +/- 3 ng/mg under the same test conditions. Basal levels of HMG CoA reductase in tumor cells of 45.2 +/- 6.5 units/mg cell protein were about twice those of normal cells. However, in contrast to the lack of feedback control of this enzyme observed with tumors in vivo, in both the normal and the transformed cells in vitro, activity of the enzyme decreased about fourfold when serum lipids were added. These findings demonstrate that tumor cells growing in vitro contain a normal complement of the membrane-located binding receptors for low density lipoproteins and, although the basal levels are higher than normal, an effective feedback regulation of the enzyme HMG CoA reductase is retained."}
{"id": "PMID:197187", "title": "Specific binding of prolactin to seminal vesicle, prostate and testicular homogenates of immature, mature and aged rats.", "content": "Ovine prolactin was iodinated by the lactoperoxidase method and purified by gel filtration on Sephadex G-100. The binding ability of the labelled hormone was determined, by incubation with liver homogenate from rabbits in late pregnancy, to be 8-8% total binding/mg protein, of which 86% was specific. The fraction of 125I-labelled ovine prolactin which bound most strongly was subsequently used to study its binding to rat seminal vesicle, prostate and testicular homogenates. The total binding to the seminal vesicle homogenate taken from mature (80-day-old) rats was the highest (11-69%/mg protein), but the greatest degree of binding specificity (82-6%) was to immature (30-day-old) rat prostate. Both total and specific binding to rat testicular homogenate were consistently very low. The binding specificity was demonstrated by displacement studies: while ovine prolactin caused displacement of specific binding, human chorionic gonadotropin, rat thyrotropin and human follicle-stimulating hormone did not cause any significant displacement of bound 125I-labelled ovine prolactin. Affinity constants (Ka) and binding capacities for the seminal vesicle and prostate homogenates were determined by Scatchard analysis and the effect of age on these parameters was studied. There was no difference in Ka between the aged (220-day-old), immature and mature rat tissue homogenates; however, a significant fall in binding capacity was observed in the mature rat prostate, and a further fall in the aged rat prostate. No such change was observed in the binding capacity of the seminal vesicle, as estimated by Scatchard analysis, although total and specific binding to the mature homogenates was higher than that of the other age groups.", "contents": "Specific binding of prolactin to seminal vesicle, prostate and testicular homogenates of immature, mature and aged rats. Ovine prolactin was iodinated by the lactoperoxidase method and purified by gel filtration on Sephadex G-100. The binding ability of the labelled hormone was determined, by incubation with liver homogenate from rabbits in late pregnancy, to be 8-8% total binding/mg protein, of which 86% was specific. The fraction of 125I-labelled ovine prolactin which bound most strongly was subsequently used to study its binding to rat seminal vesicle, prostate and testicular homogenates. The total binding to the seminal vesicle homogenate taken from mature (80-day-old) rats was the highest (11-69%/mg protein), but the greatest degree of binding specificity (82-6%) was to immature (30-day-old) rat prostate. Both total and specific binding to rat testicular homogenate were consistently very low. The binding specificity was demonstrated by displacement studies: while ovine prolactin caused displacement of specific binding, human chorionic gonadotropin, rat thyrotropin and human follicle-stimulating hormone did not cause any significant displacement of bound 125I-labelled ovine prolactin. Affinity constants (Ka) and binding capacities for the seminal vesicle and prostate homogenates were determined by Scatchard analysis and the effect of age on these parameters was studied. There was no difference in Ka between the aged (220-day-old), immature and mature rat tissue homogenates; however, a significant fall in binding capacity was observed in the mature rat prostate, and a further fall in the aged rat prostate. No such change was observed in the binding capacity of the seminal vesicle, as estimated by Scatchard analysis, although total and specific binding to the mature homogenates was higher than that of the other age groups."}
{"id": "PMID:197188", "title": "Inhibitory action of porcine follicular fluid upon granulosa cell luteinization in vitro: assay and influence of follicular maturation.", "content": "Culture medium 199 supplemented with follicular fluid from 1-2 mm antral porcine follicles inhibited spontaneous luteinization of granulosa cells from preovulatory porcine follicles in vitro. Three characteristics of luteinization were inhibited: morphological transformation, progesterone secretion, and accumulation of cyclic AMP in response to LH. The last was inhibited more effectively by culture media containing 50% follicular fluid than by media containing 20% follicular fluid. The inhibitory actions of the follicular fluid were not altered by charcoal or petroleum ether extraction. Follicular fluid from large follicles (6-12 mm) did not exhibit any of these inhibitory actions. These observations may indicate the presence of a luteinization inhibitor in the fluid of small follicles which (1) is lost by the time the follicle reaches the preovulatory stage, or (2) is overcome by a stimulatory agent which may accumulate as the follicle grows.", "contents": "Inhibitory action of porcine follicular fluid upon granulosa cell luteinization in vitro: assay and influence of follicular maturation. Culture medium 199 supplemented with follicular fluid from 1-2 mm antral porcine follicles inhibited spontaneous luteinization of granulosa cells from preovulatory porcine follicles in vitro. Three characteristics of luteinization were inhibited: morphological transformation, progesterone secretion, and accumulation of cyclic AMP in response to LH. The last was inhibited more effectively by culture media containing 50% follicular fluid than by media containing 20% follicular fluid. The inhibitory actions of the follicular fluid were not altered by charcoal or petroleum ether extraction. Follicular fluid from large follicles (6-12 mm) did not exhibit any of these inhibitory actions. These observations may indicate the presence of a luteinization inhibitor in the fluid of small follicles which (1) is lost by the time the follicle reaches the preovulatory stage, or (2) is overcome by a stimulatory agent which may accumulate as the follicle grows."}
{"id": "PMID:197189", "title": "Regulation of insulin and glucagon secretion from a human islet cell adenoma.", "content": "The regulation of insulin biosynthesis, and insulin and glucagon secretion have been investigated in a human islet cell adenoma, by incubation of tumour fragments. Both biosynthesis and secretion of insulin were strongly stimulated by incubation of islet tumour cells in the presence of increasing glucose concentrations in the range 2-8 mmol/1. However, 20 mM-glucose or 20 mM-glucose plus isobutyl methylxanthine (IBMX), both of which provide potent secretagogues for normal B cells, failed to stimulate proinsulin biosynthesis and secretion from the tumour cells. Overall rates of secretion, expressed as a proportion of total insulin content, were up to 20-fold higher than those expected for normal pancreatic tissue. Glucagon secretion from the tumour was stimulated by low glucose concentrations; normal A cells also respond in this way under these conditions. However, no stimulation of glucagon secretion occurred in the presence of IBMX. There was therefore a major alteration in the regulation both of insulin and glucagon secretion, in that release of neither hormone was stimulated by cyclic AMP. Ultrastructural examination showed the tumour to be rather heterogeneous. A and B cells with normal storage granule content and structure were seen, as well as a rather larger number of B cells containing some granules of atypical appearance. The insulin content of the tumour (13 i.u./g wet wt) was consistent with 6-8% of the tumour cells being B cells.", "contents": "Regulation of insulin and glucagon secretion from a human islet cell adenoma. The regulation of insulin biosynthesis, and insulin and glucagon secretion have been investigated in a human islet cell adenoma, by incubation of tumour fragments. Both biosynthesis and secretion of insulin were strongly stimulated by incubation of islet tumour cells in the presence of increasing glucose concentrations in the range 2-8 mmol/1. However, 20 mM-glucose or 20 mM-glucose plus isobutyl methylxanthine (IBMX), both of which provide potent secretagogues for normal B cells, failed to stimulate proinsulin biosynthesis and secretion from the tumour cells. Overall rates of secretion, expressed as a proportion of total insulin content, were up to 20-fold higher than those expected for normal pancreatic tissue. Glucagon secretion from the tumour was stimulated by low glucose concentrations; normal A cells also respond in this way under these conditions. However, no stimulation of glucagon secretion occurred in the presence of IBMX. There was therefore a major alteration in the regulation both of insulin and glucagon secretion, in that release of neither hormone was stimulated by cyclic AMP. Ultrastructural examination showed the tumour to be rather heterogeneous. A and B cells with normal storage granule content and structure were seen, as well as a rather larger number of B cells containing some granules of atypical appearance. The insulin content of the tumour (13 i.u./g wet wt) was consistent with 6-8% of the tumour cells being B cells."}
{"id": "PMID:197190", "title": "Functional activity of the hypothalamo-pituitary complex in the rat after betamethasone treatment.", "content": "The precise nature of the impairment of hypothalamo-pituitary-adrenocortical (HPA) activity which follows prolonged corticosteroid treatment is not yet understood. To study this problem, hypothalamic corticotrophin releasing hormone (CRH) content, pituitary ACTH content and the functional capacity of adenohypophysial tissue in vitro were measured in rats after treatment with betamethasone. The content of CRH and ACTH in the hypothalamus and pituitary gland respectively were markedly reduced. After stopping the treatment the hormone concentrations in both structures returned to normal with the rise in the hypothalamus preceding that in the pituitary gland. Adenohypophysial tissue from betamethasone-treated rats incubated with hypothalamic extracts from control animals showed a considerable reduction in its ability to synthesize and release ACTH. However, corticotrophin release was impaired in adenohypophyses removed from untreated rats and incubated with betamethasone but synthesis was not affected. The physiological significance and the possible clinical relevance of the results are discussed.", "contents": "Functional activity of the hypothalamo-pituitary complex in the rat after betamethasone treatment. The precise nature of the impairment of hypothalamo-pituitary-adrenocortical (HPA) activity which follows prolonged corticosteroid treatment is not yet understood. To study this problem, hypothalamic corticotrophin releasing hormone (CRH) content, pituitary ACTH content and the functional capacity of adenohypophysial tissue in vitro were measured in rats after treatment with betamethasone. The content of CRH and ACTH in the hypothalamus and pituitary gland respectively were markedly reduced. After stopping the treatment the hormone concentrations in both structures returned to normal with the rise in the hypothalamus preceding that in the pituitary gland. Adenohypophysial tissue from betamethasone-treated rats incubated with hypothalamic extracts from control animals showed a considerable reduction in its ability to synthesize and release ACTH. However, corticotrophin release was impaired in adenohypophyses removed from untreated rats and incubated with betamethasone but synthesis was not affected. The physiological significance and the possible clinical relevance of the results are discussed."}
{"id": "PMID:197191", "title": "The presence of lactogen but not growth hormone binding sites in the isolated rat hepatocyte.", "content": "The binding of 125I-labelled human growth hormone (hGH) and bovine growth hormone (bGH) has been studied in hepatocytes isolated from female rats by perfusion with collagenase in situ. The cells appeared to retain normal membrane function, in that amino acid ([14C]alpha-aminoisobutyric acid) transport was both saturable and temperature-dependent. Amino acid ([14C]leucine) incorporation into protein was also linear over 3 h and was inhibited by cycloheximide. Binding of 125I-labelled hGH was dependent on time, temperature, hepatocyte concentration and hGH concentration. At 22 degrees C, binding reached a steady-state after 2-5 h and had a half-life of dissociation of 2-3 h. Hormone specificity studies indicated that binding was specific for hormones with prolactin-like activity (hGH, prolactins) and not for growth hormones themselves (bGH). Scatchard analysis revealed a single class of binding site with a binding capacity of 26-74+/-3-73 fmol/10(6) cells and a binding affinity of 1-24 X 10(9)+/-0-17 X 10(9) (S.E.M.) 1/mol (n=10). There was a significant sex difference in binding (female greater than male) and binding was subject to marked regulation by oestrogens (stimulation of binding) and by androgens (inhibition). The lactogen-binding sites, therefore, were comparable in many respects to those previously reported in rat liver membranes. No distinct GH binding sites were demonstrable as shown by the lack of specific binding by 125I-labelled bGH, purified either by Sephadex chromatography or by binding to and elution from GH receptors in rabbit liver membranes. The value of receptor purification of tracer for use in hormone binding studies was indicated by a substantial lowering of non-specific binding.", "contents": "The presence of lactogen but not growth hormone binding sites in the isolated rat hepatocyte. The binding of 125I-labelled human growth hormone (hGH) and bovine growth hormone (bGH) has been studied in hepatocytes isolated from female rats by perfusion with collagenase in situ. The cells appeared to retain normal membrane function, in that amino acid ([14C]alpha-aminoisobutyric acid) transport was both saturable and temperature-dependent. Amino acid ([14C]leucine) incorporation into protein was also linear over 3 h and was inhibited by cycloheximide. Binding of 125I-labelled hGH was dependent on time, temperature, hepatocyte concentration and hGH concentration. At 22 degrees C, binding reached a steady-state after 2-5 h and had a half-life of dissociation of 2-3 h. Hormone specificity studies indicated that binding was specific for hormones with prolactin-like activity (hGH, prolactins) and not for growth hormones themselves (bGH). Scatchard analysis revealed a single class of binding site with a binding capacity of 26-74+/-3-73 fmol/10(6) cells and a binding affinity of 1-24 X 10(9)+/-0-17 X 10(9) (S.E.M.) 1/mol (n=10). There was a significant sex difference in binding (female greater than male) and binding was subject to marked regulation by oestrogens (stimulation of binding) and by androgens (inhibition). The lactogen-binding sites, therefore, were comparable in many respects to those previously reported in rat liver membranes. No distinct GH binding sites were demonstrable as shown by the lack of specific binding by 125I-labelled bGH, purified either by Sephadex chromatography or by binding to and elution from GH receptors in rabbit liver membranes. The value of receptor purification of tracer for use in hormone binding studies was indicated by a substantial lowering of non-specific binding."}
{"id": "PMID:197192", "title": "Cell surface antigens of chemically induced sarcomas of the mouse. I. Murine leukemia virus-related antigens and alloantigens on cultured fibroblasts and sarcoma cells: description of a unique antigen on BALB/c Meth A sarcoma.", "content": "As background for a serological definition of the unique antigens of chemically induced sarcomas, we have typed a series of fibroblast and sarcoma cell lines of BALB/c and C57BL/6 origin by cytoxicity and absorption tests for murine leukemia virus (MuLV)-related cell surface antigens and known alloantigens. 7 of the 17 cultured lines expressed the range of cell surface antigens associated with MuLV (GIX, GCSA, gp70, p30), and this was invariably associated with MuLV production. In nonproducer lines of C57BL/6 (but not BALB/c) origin, a MuLV-gp70-like molecule was found on the surface of fibroblasts and sarcoma cells. The alloantigenic phenotype of these MuLV+ and MuLV- cell lines was H-2D+, H-2K+, Thy-1.2+ or -, PC.1+ or -, Lyt-1.2-, Lyt-2.2-, Ia.7-, and TL.2-. A unique antigen was defined on the BALB/c ascites sarcoma Meth A with antisera prepared in BALB/c or (BALB/c X C57BL/6)F1 mice. Tissue culture lines derived from this tumor were MuLV-, which facilitated serological study of the antigen. Absorption analysis indicated that the antigen was restricted to Meth A; it could not be detected in normal or fetal BALB/c tissue MuLV+ or MuLV- fibroblast lines, 12 syngeneic or allogeneic sarcomas, or normal lymphoid cells from 13 different inbred mouse strains.", "contents": "Cell surface antigens of chemically induced sarcomas of the mouse. I. Murine leukemia virus-related antigens and alloantigens on cultured fibroblasts and sarcoma cells: description of a unique antigen on BALB/c Meth A sarcoma. As background for a serological definition of the unique antigens of chemically induced sarcomas, we have typed a series of fibroblast and sarcoma cell lines of BALB/c and C57BL/6 origin by cytoxicity and absorption tests for murine leukemia virus (MuLV)-related cell surface antigens and known alloantigens. 7 of the 17 cultured lines expressed the range of cell surface antigens associated with MuLV (GIX, GCSA, gp70, p30), and this was invariably associated with MuLV production. In nonproducer lines of C57BL/6 (but not BALB/c) origin, a MuLV-gp70-like molecule was found on the surface of fibroblasts and sarcoma cells. The alloantigenic phenotype of these MuLV+ and MuLV- cell lines was H-2D+, H-2K+, Thy-1.2+ or -, PC.1+ or -, Lyt-1.2-, Lyt-2.2-, Ia.7-, and TL.2-. A unique antigen was defined on the BALB/c ascites sarcoma Meth A with antisera prepared in BALB/c or (BALB/c X C57BL/6)F1 mice. Tissue culture lines derived from this tumor were MuLV-, which facilitated serological study of the antigen. Absorption analysis indicated that the antigen was restricted to Meth A; it could not be detected in normal or fetal BALB/c tissue MuLV+ or MuLV- fibroblast lines, 12 syngeneic or allogeneic sarcomas, or normal lymphoid cells from 13 different inbred mouse strains."}
{"id": "PMID:197193", "title": "Cytotoxic T-cell activation by polyribonucleotides: DNA synthesis is not required.", "content": "We have shown that cytotoxic T cells can be polyclonally activated by a short exposure to complexes of polyadenylic:polyuridylic acid (poly A:U). Activation is optimal at a dose of 100 microgram/ml poly A:U and occurs during a 2 h incubation period in the absence of antigen. Killing of allogeneic, but not syngeneic, target cells can be observed after 12 h in culture and peaks after 21-24 h in the absence of any nonspecific binding ligand. The observed cytotoxicity is mediated by T lymphocytes and dose not require accessory macrophages or DNA synthesis for the activation or expression of effector functions. These results suggest that few requirements exist for the activation of cytotoxic T cells.", "contents": "Cytotoxic T-cell activation by polyribonucleotides: DNA synthesis is not required. We have shown that cytotoxic T cells can be polyclonally activated by a short exposure to complexes of polyadenylic:polyuridylic acid (poly A:U). Activation is optimal at a dose of 100 microgram/ml poly A:U and occurs during a 2 h incubation period in the absence of antigen. Killing of allogeneic, but not syngeneic, target cells can be observed after 12 h in culture and peaks after 21-24 h in the absence of any nonspecific binding ligand. The observed cytotoxicity is mediated by T lymphocytes and dose not require accessory macrophages or DNA synthesis for the activation or expression of effector functions. These results suggest that few requirements exist for the activation of cytotoxic T cells."}
{"id": "PMID:197194", "title": "Antigenic differences in nuclear proteins of normal liver and hepatoma. Identification of a nuclear protein present in hepatocytes but absent in hepatoma cells.", "content": "A nuclear antigen was detected in the mouse liver nonhistone protein fraction by using antibodies to whole liver cells. The antigen was purified to homogeneity from perchloric acid extracts of liver tissue. It gave a single band corresponding to tool wt 21,000 in sodium dodecyl sulfate gel electrophoresis. Amino acid and carbohydrate analysis showed predominance of the acidic amino acids, lack of proline, and absence of carbohydrate. Immunofluorescence staining of liver sections confirmed the nuclear localization of the antigen. Its tissue distribution was studied by using radioimmunoassay. Of the various tissues extracted for analysis, the liver contained the highest amounts of the antigen, about 1 mug/mg of solubilized liver protein. Other tissues examined showed 2-4 percent of the amount of antigen present in the liver. Two transplantable hepatomas in C3H/HeJ and C57L/J mice, respectively, and three spontaneous C3H hepatomas showed greatly decreased levels of the antigen compared to normal liver. The amount of antigen in hepatomas varied from nondetectable to 2 percent of the amount of antigen found in the livers of the mice. The antigen was also found in the blood. The antigen was found in high concentrations (up to 13 mg/ml) in the urine of normal mice. This suggests identity with the previously known mouse urinary protein (MUP). In addition to the extremely high urinary output, the properties found to be shared by MUP and the nuclear antigen included similar serum concentrations (2-60 mug/ml), a sex difference with lower values in females, same molecular size as determined by gel filtration, and immunological identity. The nuclear localization of MUP and its disappearance from hepatomas suggest that it may have an important regulatory function.", "contents": "Antigenic differences in nuclear proteins of normal liver and hepatoma. Identification of a nuclear protein present in hepatocytes but absent in hepatoma cells. A nuclear antigen was detected in the mouse liver nonhistone protein fraction by using antibodies to whole liver cells. The antigen was purified to homogeneity from perchloric acid extracts of liver tissue. It gave a single band corresponding to tool wt 21,000 in sodium dodecyl sulfate gel electrophoresis. Amino acid and carbohydrate analysis showed predominance of the acidic amino acids, lack of proline, and absence of carbohydrate. Immunofluorescence staining of liver sections confirmed the nuclear localization of the antigen. Its tissue distribution was studied by using radioimmunoassay. Of the various tissues extracted for analysis, the liver contained the highest amounts of the antigen, about 1 mug/mg of solubilized liver protein. Other tissues examined showed 2-4 percent of the amount of antigen present in the liver. Two transplantable hepatomas in C3H/HeJ and C57L/J mice, respectively, and three spontaneous C3H hepatomas showed greatly decreased levels of the antigen compared to normal liver. The amount of antigen in hepatomas varied from nondetectable to 2 percent of the amount of antigen found in the livers of the mice. The antigen was also found in the blood. The antigen was found in high concentrations (up to 13 mg/ml) in the urine of normal mice. This suggests identity with the previously known mouse urinary protein (MUP). In addition to the extremely high urinary output, the properties found to be shared by MUP and the nuclear antigen included similar serum concentrations (2-60 mug/ml), a sex difference with lower values in females, same molecular size as determined by gel filtration, and immunological identity. The nuclear localization of MUP and its disappearance from hepatomas suggest that it may have an important regulatory function."}
{"id": "PMID:197195", "title": "Genetic control of radiation leukemia virus-induced tumorigenesis. I. Role of the major murine histocompatibility complex, H-2.", "content": "Resistance to radiation leukemia virus-induced leukemogenesis is associated with the H-2D region of the H-2 complex, or with closely linked loci. The H-2Dd allele confers resistance ot the disease, while the H-2D-Q and H-2Ds alleles are associated with susceptibility. It is not clear whether Ir genes, or an alternative mechanism are responsible for the observed H-2-linked resistance to the disease.", "contents": "Genetic control of radiation leukemia virus-induced tumorigenesis. I. Role of the major murine histocompatibility complex, H-2. Resistance to radiation leukemia virus-induced leukemogenesis is associated with the H-2D region of the H-2 complex, or with closely linked loci. The H-2Dd allele confers resistance ot the disease, while the H-2D-Q and H-2Ds alleles are associated with susceptibility. It is not clear whether Ir genes, or an alternative mechanism are responsible for the observed H-2-linked resistance to the disease."}
{"id": "PMID:197196", "title": "Genetic control of radiation leukemia virus-induced tumorigenesis II. Influence of Srlv-1, a locus not linked to H-2.", "content": "A single locus, tentatively denoted Srlv-1 (susceptibility to radiation leukemia virus [RadLV]-1), confers dominant susceptibility to RadLV-induced leukemogenesis. Srlv-1 is not linked to H-2, and appears to be distinct from Fv-1 and Fv-2. Preliminary data suggest that Srlv-1 affected virus proliferation. A striking feature of this system is that Srlv-1 overrides the protection afforded by the H2D-associated dominant resistance to RadLV-induced neoplasia.", "contents": "Genetic control of radiation leukemia virus-induced tumorigenesis II. Influence of Srlv-1, a locus not linked to H-2. A single locus, tentatively denoted Srlv-1 (susceptibility to radiation leukemia virus [RadLV]-1), confers dominant susceptibility to RadLV-induced leukemogenesis. Srlv-1 is not linked to H-2, and appears to be distinct from Fv-1 and Fv-2. Preliminary data suggest that Srlv-1 affected virus proliferation. A striking feature of this system is that Srlv-1 overrides the protection afforded by the H2D-associated dominant resistance to RadLV-induced neoplasia."}
{"id": "PMID:197197", "title": "Resistance genes to murine leukemia in the I immune response gene region of the H-2 complex.", "content": "A resistance locus to leukemogenesis in mice by A-RadLV (a variant of the radiation leukemia virus) is described. This locus, Rrv-1, was mapped to subregions I-A, I-B, and I-J of the H-2 complex. It is suggested that Rrv-1 may be in complementation with a second locus to the right of it, between Rrv-1 and H-2D. This localization and the complementation of the two loci for resistance are characteristics similar to Ir genes, and indicate a possible relationship between the genetic regulation of immune responsiveness and susceptibility to leukemia.", "contents": "Resistance genes to murine leukemia in the I immune response gene region of the H-2 complex. A resistance locus to leukemogenesis in mice by A-RadLV (a variant of the radiation leukemia virus) is described. This locus, Rrv-1, was mapped to subregions I-A, I-B, and I-J of the H-2 complex. It is suggested that Rrv-1 may be in complementation with a second locus to the right of it, between Rrv-1 and H-2D. This localization and the complementation of the two loci for resistance are characteristics similar to Ir genes, and indicate a possible relationship between the genetic regulation of immune responsiveness and susceptibility to leukemia."}
{"id": "PMID:197198", "title": "Exclusive involvement of H-2Db or H-2Kd product in the interaction between T-killer lymphocytes and syngeneic H-2b or H-2d viral lymphomas.", "content": "It was demonstrated previously that the cytolysis of murine viral lymphoma cells by anti-murine sarcoma virus (MSV) syngeneic T-killer lymphocytes was restricted by some products of the H-2 complex. The respective role of the products of different regions of the H-2 complex were studied with six H-2(b) and three H-2(d) lymphomas induced by five different type C viruses. They were tested in a classical chromium release test against anti-MSV T-killer cells obtained from different inbred strains of mice, including several H-2 recombinants. Tumors o pound the H-2(b) haplotype were lysed only when effectors and target cells have in common the D(b) region. On the contrary an identity limited to the K end of the H-2 complex is necessary and sufficient in the H-2(d) haplotype. An in vitro restimulation of the spleen cells with concanavalin A strongly increased the activity of in vivo-primed T lymphocytes but did not provide any response for in vivo-primed but nonresponder cells. Preincubation of the tumor cells with anti-H-2 sera abolished the lysis by syngeneic anti-MSV effector lymphocytes. The same results were obtained by preincubating the H-2(b) targets with anti-H-2D(b), or the H-2(d) target with anti-H-2K(d). Preincubation with anti-H-2K(b) or anti- H-2D(d) were ineffective. These results show that the T-killer/target cells interaction in the MSV system involved some products of the H-2 complex which might be different with the various H-2 haplotypes and could possibly vary according to the antigenic specificity. A specific association of a viral product with a normal cellular structure, directed by the H-2 region during the viral budding could explain the observed results.", "contents": "Exclusive involvement of H-2Db or H-2Kd product in the interaction between T-killer lymphocytes and syngeneic H-2b or H-2d viral lymphomas. It was demonstrated previously that the cytolysis of murine viral lymphoma cells by anti-murine sarcoma virus (MSV) syngeneic T-killer lymphocytes was restricted by some products of the H-2 complex. The respective role of the products of different regions of the H-2 complex were studied with six H-2(b) and three H-2(d) lymphomas induced by five different type C viruses. They were tested in a classical chromium release test against anti-MSV T-killer cells obtained from different inbred strains of mice, including several H-2 recombinants. Tumors o pound the H-2(b) haplotype were lysed only when effectors and target cells have in common the D(b) region. On the contrary an identity limited to the K end of the H-2 complex is necessary and sufficient in the H-2(d) haplotype. An in vitro restimulation of the spleen cells with concanavalin A strongly increased the activity of in vivo-primed T lymphocytes but did not provide any response for in vivo-primed but nonresponder cells. Preincubation of the tumor cells with anti-H-2 sera abolished the lysis by syngeneic anti-MSV effector lymphocytes. The same results were obtained by preincubating the H-2(b) targets with anti-H-2D(b), or the H-2(d) target with anti-H-2K(d). Preincubation with anti-H-2K(b) or anti- H-2D(d) were ineffective. These results show that the T-killer/target cells interaction in the MSV system involved some products of the H-2 complex which might be different with the various H-2 haplotypes and could possibly vary according to the antigenic specificity. A specific association of a viral product with a normal cellular structure, directed by the H-2 region during the viral budding could explain the observed results."}
{"id": "PMID:197199", "title": "[Differentiation of VLDL subfraction in the diagnosis of type III hyperlipoproteinaemias (author's transl)].", "content": "Type III hyperlipoproteinaemias are characterized by \"floating\" beta-lipoproteins. In lipid electrophoresis these are present as a VLDL subfraction (beta-VLDL). They can also be detected chemically on the basis of the cholesterol/triglyceride ratio of the serum or the corresponding VLDL serum fraction. In the present work, the diagnostic value of these ratios is compared with that of E III peptide loss from VLDL-apolipoproteins, which is thought to be specific for type III hyperlipoproteinaemias. Of 42 persons with a VLDL subfraction, seven showed a loss of the peptide. In these persons, the cholesterol/triglyceride quotient was 0.94+/-0.45 for the whole serum, and 0.59+/-0.25 for the serum VLDL fraction. The quotient for VLDL cholesterol/serum triglyceride was 0.43+/-0,21, and the electrophoretic mobility of the VLDL subfraction was 0.38+/-0.04. Investigation of the VLDL-cholesterol/triglyceride quotient gave four (10%) false positives, while the quotient for VLDL-cholesterol/serum triglyceride gave ten (24%) false positives. This comparison shows that the criteria used for identification of \"floating\" beta-VLDL subfraction are only indirectly useful in the diagnosis of type III hyperlipoproteinaemia.", "contents": "[Differentiation of VLDL subfraction in the diagnosis of type III hyperlipoproteinaemias (author's transl)]. Type III hyperlipoproteinaemias are characterized by \"floating\" beta-lipoproteins. In lipid electrophoresis these are present as a VLDL subfraction (beta-VLDL). They can also be detected chemically on the basis of the cholesterol/triglyceride ratio of the serum or the corresponding VLDL serum fraction. In the present work, the diagnostic value of these ratios is compared with that of E III peptide loss from VLDL-apolipoproteins, which is thought to be specific for type III hyperlipoproteinaemias. Of 42 persons with a VLDL subfraction, seven showed a loss of the peptide. In these persons, the cholesterol/triglyceride quotient was 0.94+/-0.45 for the whole serum, and 0.59+/-0.25 for the serum VLDL fraction. The quotient for VLDL cholesterol/serum triglyceride was 0.43+/-0,21, and the electrophoretic mobility of the VLDL subfraction was 0.38+/-0.04. Investigation of the VLDL-cholesterol/triglyceride quotient gave four (10%) false positives, while the quotient for VLDL-cholesterol/serum triglyceride gave ten (24%) false positives. This comparison shows that the criteria used for identification of \"floating\" beta-VLDL subfraction are only indirectly useful in the diagnosis of type III hyperlipoproteinaemia."}
{"id": "PMID:197201", "title": "The analysis of nonlinear synaptic transmission.", "content": "In order to characterize synaptic transmission at a unitary facilitating synapse in the lobster cardiac ganglion, a new nonlinear systems analysis technique for discrete-input systems was developed and applied. From the output of the postsynaptic cell in response to randomly occurring presynaptic nerve impulses, a set of kernels, analogous to Wiener kernels, was computed. The kernels up to third order served to characterize, with reasonable accuracy, the input-output properties of the synapse. A mathematical model of the synapse was also tested with a random impulse train and model predictions were compared with experimental synaptic output. Although the model proved to be even more accurate overall than the kernel characterization, there were slight but consistent errors in the model's performance. These were also reflected as differences between model and experimental kernels. It is concluded that a random train analysis provides a comprehensive and objective comparison between model and experiment and automatically provides an arbitrarily accurate characterization of a system's input-output behavior, even in complicated cases where other approaches are impractical.", "contents": "The analysis of nonlinear synaptic transmission. In order to characterize synaptic transmission at a unitary facilitating synapse in the lobster cardiac ganglion, a new nonlinear systems analysis technique for discrete-input systems was developed and applied. From the output of the postsynaptic cell in response to randomly occurring presynaptic nerve impulses, a set of kernels, analogous to Wiener kernels, was computed. The kernels up to third order served to characterize, with reasonable accuracy, the input-output properties of the synapse. A mathematical model of the synapse was also tested with a random impulse train and model predictions were compared with experimental synaptic output. Although the model proved to be even more accurate overall than the kernel characterization, there were slight but consistent errors in the model's performance. These were also reflected as differences between model and experimental kernels. It is concluded that a random train analysis provides a comprehensive and objective comparison between model and experiment and automatically provides an arbitrarily accurate characterization of a system's input-output behavior, even in complicated cases where other approaches are impractical."}
{"id": "PMID:197202", "title": "Isolation and preliminary characterization of temperature-sensitive mutants of the murine sarcoma leukaemia virus complex.", "content": "Five temperature-sensitive mutants (ts I to 5) were isolated from a stock of the Moloney strain of murine sarcoma leukaemia virus complex which had been mutagenized by ultraviolet irradiation or N-methyl-N'-nitro-N-nitrosoguanidine. In mouse cells at the non-permissive temperature the mutants formed fewer foci of transformed cells than at the permissive temperature. The ts mutants were characterized by testing: (I) murine leukaemia virus (MuLV) clones from the ts complex, (2) the effect of additional wild type MuLV on focus formation, (3) focus formation in rat cells and (4) focus formation with pseudotypes rescued from non-producer cells. Two mutants (ts 1 and ts 3) were found to be ts MuLVs which did not possess heat labile virion proteins and were not ts in post-penetration helper functions necessary for the fixation of sarcoma virus transformation. The remaining three mutants (ts 2, ts 4 and ts 5) were ts murine sarcoma viruses which, however, showed no temperature-sensitive effect on the maintenance of transformed cell morphology nor on colony forming efficiency in soft agar.", "contents": "Isolation and preliminary characterization of temperature-sensitive mutants of the murine sarcoma leukaemia virus complex. Five temperature-sensitive mutants (ts I to 5) were isolated from a stock of the Moloney strain of murine sarcoma leukaemia virus complex which had been mutagenized by ultraviolet irradiation or N-methyl-N'-nitro-N-nitrosoguanidine. In mouse cells at the non-permissive temperature the mutants formed fewer foci of transformed cells than at the permissive temperature. The ts mutants were characterized by testing: (I) murine leukaemia virus (MuLV) clones from the ts complex, (2) the effect of additional wild type MuLV on focus formation, (3) focus formation in rat cells and (4) focus formation with pseudotypes rescued from non-producer cells. Two mutants (ts 1 and ts 3) were found to be ts MuLVs which did not possess heat labile virion proteins and were not ts in post-penetration helper functions necessary for the fixation of sarcoma virus transformation. The remaining three mutants (ts 2, ts 4 and ts 5) were ts murine sarcoma viruses which, however, showed no temperature-sensitive effect on the maintenance of transformed cell morphology nor on colony forming efficiency in soft agar."}
{"id": "PMID:197203", "title": "Antiviral activity of bovine interferons on primate cells.", "content": "Potent preparations of bovine leucocyte and fibroblast interferons had substantial antiviral activity on monkey cells and low activity on human cells. Thus, interferon from a 'lower' phylogenetic species can have considerable antiviral activity in primate cells, but not all primate cells are equally sensitive.", "contents": "Antiviral activity of bovine interferons on primate cells. Potent preparations of bovine leucocyte and fibroblast interferons had substantial antiviral activity on monkey cells and low activity on human cells. Thus, interferon from a 'lower' phylogenetic species can have considerable antiviral activity in primate cells, but not all primate cells are equally sensitive."}
{"id": "PMID:197204", "title": "Human cytomegalovirus: purification of enveloped virions and dense bodies.", "content": "Enveloped virions and dense bodies of human cytomegalovirus have been purified by centrifugation, using combination negative viscosity: positive density gradients. Light-scattering bands of each component were obtained, and when these were examined by immune electron microscopy minimal cross contamination was observed.", "contents": "Human cytomegalovirus: purification of enveloped virions and dense bodies. Enveloped virions and dense bodies of human cytomegalovirus have been purified by centrifugation, using combination negative viscosity: positive density gradients. Light-scattering bands of each component were obtained, and when these were examined by immune electron microscopy minimal cross contamination was observed."}
{"id": "PMID:197205", "title": "Protection of mice against encephalomyocarditis virus infection by chemically modified transfer RNAs.", "content": "Periodate or nitrous acid treatment greatly decreases the ability of unfractionated Escherichia coli transfer RNA (tRNA) to be aminoacylated by tRNA-synthetases but these treatments do not affect their antiviral activity against encephalomyocarditis virus infection of mice. Bisulphite treatment of E. coli tRNA reduces its ability to be aminoacylated by 20% and has no effect on antiviral activity. Bromine water treatment of tRNA under conditions causing extensive base modifications eliminates aminoacylation and the antiviral activity of E. coli tRNA. Periodate treatment of yeast tRNA does not affect its antiviral activity and nitrous acid treatment increases its antiviral activity to that of E. coli tRNA. The ability to be aminoacylated does not therefore appear to be essential for antiviral activity of tRNA but extensive modification (bromine water treatment) does destroy antiviral activity.", "contents": "Protection of mice against encephalomyocarditis virus infection by chemically modified transfer RNAs. Periodate or nitrous acid treatment greatly decreases the ability of unfractionated Escherichia coli transfer RNA (tRNA) to be aminoacylated by tRNA-synthetases but these treatments do not affect their antiviral activity against encephalomyocarditis virus infection of mice. Bisulphite treatment of E. coli tRNA reduces its ability to be aminoacylated by 20% and has no effect on antiviral activity. Bromine water treatment of tRNA under conditions causing extensive base modifications eliminates aminoacylation and the antiviral activity of E. coli tRNA. Periodate treatment of yeast tRNA does not affect its antiviral activity and nitrous acid treatment increases its antiviral activity to that of E. coli tRNA. The ability to be aminoacylated does not therefore appear to be essential for antiviral activity of tRNA but extensive modification (bromine water treatment) does destroy antiviral activity."}
{"id": "PMID:197210", "title": "Refractory period, conduction of trains of impulses, and effect of temperature on conduction in chronic hypertrophic neuropathy.", "content": "The refractory period, the ability to transmit trains of impulses, and the effect of temperature on conduction, have been studied in the sciatic-tibial nerve trunks of Trembler mice, which suffer from a dominantly inherited hypertrophic neuropathy. Both the refractory period of transmission and the relative refractory period were increased in Trembler mice when compared with controls. The nerve trunks of Trembler mice were unable to conduct rapid trains of impulses, and conduction block occurred at rates of stimulation as low as 25 Hz. Cold block occurred at temperatures significantly higher in Trembler nerves than in controls. The conduction velocity increased in an approximately linear fashion in both Trembler and control nerves when the temperature was raised from 20 degrees C to 40 degrees C, and the slopes were not significantly different. The Q10 (27 degrees C-37 degrees C) was 1.5 and 1.6 for control and Trembler nerves respectively. Conduction block was regularly observed in Trembler nerves when the temperature was raised within the physiological range. The abnormalities are related to the pathological changes of chronic demyelination.", "contents": "Refractory period, conduction of trains of impulses, and effect of temperature on conduction in chronic hypertrophic neuropathy. The refractory period, the ability to transmit trains of impulses, and the effect of temperature on conduction, have been studied in the sciatic-tibial nerve trunks of Trembler mice, which suffer from a dominantly inherited hypertrophic neuropathy. Both the refractory period of transmission and the relative refractory period were increased in Trembler mice when compared with controls. The nerve trunks of Trembler mice were unable to conduct rapid trains of impulses, and conduction block occurred at rates of stimulation as low as 25 Hz. Cold block occurred at temperatures significantly higher in Trembler nerves than in controls. The conduction velocity increased in an approximately linear fashion in both Trembler and control nerves when the temperature was raised from 20 degrees C to 40 degrees C, and the slopes were not significantly different. The Q10 (27 degrees C-37 degrees C) was 1.5 and 1.6 for control and Trembler nerves respectively. Conduction block was regularly observed in Trembler nerves when the temperature was raised within the physiological range. The abnormalities are related to the pathological changes of chronic demyelination."}
{"id": "PMID:197211", "title": "The motor unit in psychotic patients: a single fibre EMG study.", "content": "Single fibre EMG recording from extensor digitorum communis muscle is described in patients with psychotic illness. The fibre density, or average number of single muscle fibre action potentials belonging to the same motor unit within the uptake area of the electrode, was higher in the patient group than in normal controls. Increased jitter was occasionally seen. Motor and sensory nerve conduction velocity values were within the normal range. The results indicate that psychosis is associated with denervation and reinnervation by collateral sprouting.", "contents": "The motor unit in psychotic patients: a single fibre EMG study. Single fibre EMG recording from extensor digitorum communis muscle is described in patients with psychotic illness. The fibre density, or average number of single muscle fibre action potentials belonging to the same motor unit within the uptake area of the electrode, was higher in the patient group than in normal controls. Increased jitter was occasionally seen. Motor and sensory nerve conduction velocity values were within the normal range. The results indicate that psychosis is associated with denervation and reinnervation by collateral sprouting."}
{"id": "PMID:197214", "title": "Evidence for dopamine-storing interneurons and paraneurons in rhesus monkey sympathetic ganglia.", "content": "In order to study and quantify the small, intensely fluorescent (SIF) cells and to examine their synaptology, the superior cervical sympathetic ganglia of rhesus monkeys were examined by a sequential glyoxylic acid (GA) monoamine fluorescence and electron microscopic technique. Correlated data concerning the sensitivity of the ganglia to dopamine were gathered by measuring the rise in cyclic AMP levels following incubation in vitro with exogenous dopamine. Cyclic AMP levels after incubation for 12 min with 50 micron dopamine showed marked increases, averaging 288% of control values. This indicates that these ganglia contain a dopamine receptor-adenylate cyclase complex. The number of SIF cells per mg of tissue was about half that found in the cow and rabbit, and only 1% of the number observed in the rat. Morphological data support the view that, in this species, there are almost equal numbers of type I (hypothesized interneuron) and type II (paraneuron) SIF cells. Presumptive SIF cell efferent synapses were observed by electron microscopy, the postsynaptic elements being dendritic spines or very fine nerve processes.", "contents": "Evidence for dopamine-storing interneurons and paraneurons in rhesus monkey sympathetic ganglia. In order to study and quantify the small, intensely fluorescent (SIF) cells and to examine their synaptology, the superior cervical sympathetic ganglia of rhesus monkeys were examined by a sequential glyoxylic acid (GA) monoamine fluorescence and electron microscopic technique. Correlated data concerning the sensitivity of the ganglia to dopamine were gathered by measuring the rise in cyclic AMP levels following incubation in vitro with exogenous dopamine. Cyclic AMP levels after incubation for 12 min with 50 micron dopamine showed marked increases, averaging 288% of control values. This indicates that these ganglia contain a dopamine receptor-adenylate cyclase complex. The number of SIF cells per mg of tissue was about half that found in the cow and rabbit, and only 1% of the number observed in the rat. Morphological data support the view that, in this species, there are almost equal numbers of type I (hypothesized interneuron) and type II (paraneuron) SIF cells. Presumptive SIF cell efferent synapses were observed by electron microscopy, the postsynaptic elements being dendritic spines or very fine nerve processes."}
{"id": "PMID:197215", "title": "Cyclic AMP and GMP levels in thymocytes and splenic T and B lymphocytes in protein deprived rats.", "content": "Cyclic nucleotide levels were determined in thymocytes and in splenic T and B lymphocytes separated by nylon wool filtration. In control rats, thymocytes contained less cAMP and cGMP than splenic T cells. The level of cGMP was lower, and consequently cAMP:cGMP ratio was higher in splenic B than in T cells. Protein deprivation increased the nucleotide ratios in both T and B splenic lymphocytes; this effects was due to a decrease in the cGMP levels in the case of the T cells and to an increase in the cAMP levels in the B cells. These data could be related to the reduced mitotic activity of the splenic lymphocytes. However, the nylon-nonadherent thmyocytes of protein deprived rats paradoxically displayed increased cGMP contents without changes in the cAMP levels, despite the drop in their proliferative potential. The impairment of cyclic nucleotide metabolism may intervene in the immunological disturbances due to protein malnutrition.", "contents": "Cyclic AMP and GMP levels in thymocytes and splenic T and B lymphocytes in protein deprived rats. Cyclic nucleotide levels were determined in thymocytes and in splenic T and B lymphocytes separated by nylon wool filtration. In control rats, thymocytes contained less cAMP and cGMP than splenic T cells. The level of cGMP was lower, and consequently cAMP:cGMP ratio was higher in splenic B than in T cells. Protein deprivation increased the nucleotide ratios in both T and B splenic lymphocytes; this effects was due to a decrease in the cGMP levels in the case of the T cells and to an increase in the cAMP levels in the B cells. These data could be related to the reduced mitotic activity of the splenic lymphocytes. However, the nylon-nonadherent thmyocytes of protein deprived rats paradoxically displayed increased cGMP contents without changes in the cAMP levels, despite the drop in their proliferative potential. The impairment of cyclic nucleotide metabolism may intervene in the immunological disturbances due to protein malnutrition."}
{"id": "PMID:197216", "title": "Biohydrogenation and availability of linoleic acid in lactating cows.", "content": "Linoleic acid biohydrogenation, absorption and availability for maintenance and milk production in dairy cows fed high grain (60--85% of dry matter) diets were quantitatively estimated by isotope dilution, using two methods of dosing. [1-14C]Linoleic acid-labeled chylomicra and very low density lipoproteins (VLDL) were obtained from lymph of a calf fed [1-14C]linoleic acid and fitted with a thoracic duct-venous shunt. Labeled chylomicra were injected intravenously into two cows: a Jersey (trial 1), and a Holstein (trial 2). Labeled VLDL was injected intravenously into a Holstein cow (trial 3). In trials 4 and 5 the [1-14C]linoleic acid was placed into the omasal canal of two rumen-fistulated Holstein cows. Linoleic acid biohydrogenation (%), absorption (g/day), and availability above requirements for milk production (mg/kg body wt 3/4) were: 68.1 +/- 2.28, 52.1 +/- 2.92, and 244 +/- 19.4 (mean +/- SE), respectively. The biohydrogenation data indicate that both methods of dosing the cows were equally dependable. The estimates of linoleic acid biohydrogenation are consistent with limited data previously reported, indicating that the isotope dilution technique used is a reliable method to estimate linoleic acid absorption in lactating cows. Linoleic acid available to the lactating cow above milk production requirements was more than double the requirement of weanling female rats, when compared on the basis of metabolis body size.", "contents": "Biohydrogenation and availability of linoleic acid in lactating cows. Linoleic acid biohydrogenation, absorption and availability for maintenance and milk production in dairy cows fed high grain (60--85% of dry matter) diets were quantitatively estimated by isotope dilution, using two methods of dosing. [1-14C]Linoleic acid-labeled chylomicra and very low density lipoproteins (VLDL) were obtained from lymph of a calf fed [1-14C]linoleic acid and fitted with a thoracic duct-venous shunt. Labeled chylomicra were injected intravenously into two cows: a Jersey (trial 1), and a Holstein (trial 2). Labeled VLDL was injected intravenously into a Holstein cow (trial 3). In trials 4 and 5 the [1-14C]linoleic acid was placed into the omasal canal of two rumen-fistulated Holstein cows. Linoleic acid biohydrogenation (%), absorption (g/day), and availability above requirements for milk production (mg/kg body wt 3/4) were: 68.1 +/- 2.28, 52.1 +/- 2.92, and 244 +/- 19.4 (mean +/- SE), respectively. The biohydrogenation data indicate that both methods of dosing the cows were equally dependable. The estimates of linoleic acid biohydrogenation are consistent with limited data previously reported, indicating that the isotope dilution technique used is a reliable method to estimate linoleic acid absorption in lactating cows. Linoleic acid available to the lactating cow above milk production requirements was more than double the requirement of weanling female rats, when compared on the basis of metabolis body size."}
{"id": "PMID:197212", "title": "Mannosidosis: pathology of the nervous system.", "content": "In a girl with mannosidosis, who died at 3 1/2 years of age, histopathological and ultrastructural changes in the nervous system are described. A widespread neuronal storage evidenced by ballooning of the neuronal perikarya is the salient histological feature and the occurrence of electron-lucent storage vacuoloes in neurons, astrocytes, endothelial cells and pericytes is the most striking ultrastructural feature of mannosidosis in the nervous system. By virtue of the deficiency of acidic alpha-mannosidases A and B, the accumulation of mannose-containing oligosaccharides in tissues and the occurrence of storage vacuoles in various cells, mannoisidosis is similar to various neuronal storage diseases associated with lysosomal enzyme deficiencies. In mannosidosis, the storage vacuoles in the neural and visceral tissues are alike with little variation in details and contain chiefly loosely dispersed, finely reticulogranular material. The storage vacuoles in neurons in mannosidosis are, therefore, distinct from those in neurons in other lysosomal storage disease such as Pompe's disease, various lipidoses and mucopolysaccharidoses. However, they resemble closely the storage vacuoles in neurons in fucosidosis and those in liver cells in various mucopolysaccharidoses.", "contents": "Mannosidosis: pathology of the nervous system. In a girl with mannosidosis, who died at 3 1/2 years of age, histopathological and ultrastructural changes in the nervous system are described. A widespread neuronal storage evidenced by ballooning of the neuronal perikarya is the salient histological feature and the occurrence of electron-lucent storage vacuoloes in neurons, astrocytes, endothelial cells and pericytes is the most striking ultrastructural feature of mannosidosis in the nervous system. By virtue of the deficiency of acidic alpha-mannosidases A and B, the accumulation of mannose-containing oligosaccharides in tissues and the occurrence of storage vacuoles in various cells, mannoisidosis is similar to various neuronal storage diseases associated with lysosomal enzyme deficiencies. In mannosidosis, the storage vacuoles in the neural and visceral tissues are alike with little variation in details and contain chiefly loosely dispersed, finely reticulogranular material. The storage vacuoles in neurons in mannosidosis are, therefore, distinct from those in neurons in other lysosomal storage disease such as Pompe's disease, various lipidoses and mucopolysaccharidoses. However, they resemble closely the storage vacuoles in neurons in fucosidosis and those in liver cells in various mucopolysaccharidoses."}
{"id": "PMID:197213", "title": "The effects of nortriptyline and mesoridazine on neurons and glia in vitro.", "content": "The ultrastructural changes produced by Mesoridazine and Nortriptyline in neurons and glia in vitro are reported. Concentrically laminated bodies (CLB) and increased numbers of dense bodies were produced by exposure to these drugs. The number and complexity of the CLB increased with increased dose and longer time in vitro and their formation appeared to be reversible.", "contents": "The effects of nortriptyline and mesoridazine on neurons and glia in vitro. The ultrastructural changes produced by Mesoridazine and Nortriptyline in neurons and glia in vitro are reported. Concentrically laminated bodies (CLB) and increased numbers of dense bodies were produced by exposure to these drugs. The number and complexity of the CLB increased with increased dose and longer time in vitro and their formation appeared to be reversible."}
{"id": "PMID:197218", "title": "Arsenical neuropathy: residual effects following acute industrial exposure.", "content": "A case report is presented describing a worker who was splashed with arsenic acid in an industrial accident and subsequently developed symptoms of systemic arsenicalism and peripheral neuropathy. This is the only report, to the authors' knowledge, of a single episode of cutaneous absorption of arsenic resulting in peripheral neuropathy. Previous reports of arsenical neuropathy and rationale for BAL therapy early in the treatment of systemic arsenicalism are discussed.", "contents": "Arsenical neuropathy: residual effects following acute industrial exposure. A case report is presented describing a worker who was splashed with arsenic acid in an industrial accident and subsequently developed symptoms of systemic arsenicalism and peripheral neuropathy. This is the only report, to the authors' knowledge, of a single episode of cutaneous absorption of arsenic resulting in peripheral neuropathy. Previous reports of arsenical neuropathy and rationale for BAL therapy early in the treatment of systemic arsenicalism are discussed."}
{"id": "PMID:197220", "title": "Vaccine-associated poliomyelitis in a child with sex-linked agammaglobulinemia.", "content": "Paralytic poliomyelitis was observed in a child with a sex-linked defect in immunoglobulin synthesis. Evidence is presented that this was secondary to administration of oral, live poliovaccine. The demonstration of a familial sex-linked gammaglobulin deficiency and the failure to document a defect in cell-mediated immunity in this child extends the risk of vaccine associated poliomyelitis to virtually all forms of immunodeficiency. The critical host factors in the pathogenesis of poliovirus vaccine infection and in particular its unfavorable outcome appear to include either a deficiency in the humoral (B cell) system or in the cell-mediated (T cell) system.", "contents": "Vaccine-associated poliomyelitis in a child with sex-linked agammaglobulinemia. Paralytic poliomyelitis was observed in a child with a sex-linked defect in immunoglobulin synthesis. Evidence is presented that this was secondary to administration of oral, live poliovaccine. The demonstration of a familial sex-linked gammaglobulin deficiency and the failure to document a defect in cell-mediated immunity in this child extends the risk of vaccine associated poliomyelitis to virtually all forms of immunodeficiency. The critical host factors in the pathogenesis of poliovirus vaccine infection and in particular its unfavorable outcome appear to include either a deficiency in the humoral (B cell) system or in the cell-mediated (T cell) system."}
{"id": "PMID:197221", "title": "Bronchial carcinoid tumors in children and adolescents.", "content": "Thirteen histologically proven cases of bronchial carcinoid from the literature and eight cases from the Armed Forces Tumor Registry, all under 20 yr of age, are presented. Hemoptysis, cough, and pneumonia were the most frequent presenting complaints. Bronchoscopy defined the lesion in all 16 cases so studied. Gross and microscopic pathology is briefly described, and treatment in these cases outlined. A good long-term prognosis can be expected, except in those cases with a long delay in diagnosis.", "contents": "Bronchial carcinoid tumors in children and adolescents. Thirteen histologically proven cases of bronchial carcinoid from the literature and eight cases from the Armed Forces Tumor Registry, all under 20 yr of age, are presented. Hemoptysis, cough, and pneumonia were the most frequent presenting complaints. Bronchoscopy defined the lesion in all 16 cases so studied. Gross and microscopic pathology is briefly described, and treatment in these cases outlined. A good long-term prognosis can be expected, except in those cases with a long delay in diagnosis."}
{"id": "PMID:197222", "title": "Pleural effusion in Wilms' tumor.", "content": "The association of pleural effusion and Wilms' tumor is uncommon. We report three patients who developed pleural effusion as a result of different mechanisms, all of which were related to Wilms' tumor or to its treatment.", "contents": "Pleural effusion in Wilms' tumor. The association of pleural effusion and Wilms' tumor is uncommon. We report three patients who developed pleural effusion as a result of different mechanisms, all of which were related to Wilms' tumor or to its treatment."}
{"id": "PMID:197223", "title": "Cultural characteristics of mesoblastic nephromas.", "content": "Seven infants and children with renal tumors underwent nephrectomy and the tumors were cultured to investigate the behavior of their cells. In four children over 1 year of age with histologically typical nephroblastoma in the tumor cells were bizarre and disorderly. In one patient 3 months of age where the histology suggested malignancy the tumor culture showed an orderly growth pattern of spindle cells akin to normal kidney and the patient has had no recurrence for 18 months. In one infant seven months of age the histology was consistent with malignancy and this was confirmed on culture showing bizarre cells similar to those of nephroblastoma. The third infant under 1 year of age had a teratoma on histology and an unusual growth pattern on culture characterised by polyhedral cells with long processes and much overlapping. It is suggested that in infants with kidney tumors, tissue culture be used to help in assessing the malignant potential of the tumor and deciding on adjuvant therapy.", "contents": "Cultural characteristics of mesoblastic nephromas. Seven infants and children with renal tumors underwent nephrectomy and the tumors were cultured to investigate the behavior of their cells. In four children over 1 year of age with histologically typical nephroblastoma in the tumor cells were bizarre and disorderly. In one patient 3 months of age where the histology suggested malignancy the tumor culture showed an orderly growth pattern of spindle cells akin to normal kidney and the patient has had no recurrence for 18 months. In one infant seven months of age the histology was consistent with malignancy and this was confirmed on culture showing bizarre cells similar to those of nephroblastoma. The third infant under 1 year of age had a teratoma on histology and an unusual growth pattern on culture characterised by polyhedral cells with long processes and much overlapping. It is suggested that in infants with kidney tumors, tissue culture be used to help in assessing the malignant potential of the tumor and deciding on adjuvant therapy."}
{"id": "PMID:197224", "title": "A case of EMG (exomphalos, macroglossia, and gigantism) syndrome with associated renal tumor.", "content": "This is a brief report of a patient with Wiedemann-Beckwith syndrome and nephroblastoma with metastases, apparently cured by surgery, chemotherapy, and radiation.", "contents": "A case of EMG (exomphalos, macroglossia, and gigantism) syndrome with associated renal tumor. This is a brief report of a patient with Wiedemann-Beckwith syndrome and nephroblastoma with metastases, apparently cured by surgery, chemotherapy, and radiation."}
{"id": "PMID:197225", "title": "Wilms' tumor in crossed fused renal ectopia.", "content": "The occurrence of a nephroblastoma in a crossed ectopic kidney has been reported only one previous time. A second patient with these findings is the subject of this report.", "contents": "Wilms' tumor in crossed fused renal ectopia. The occurrence of a nephroblastoma in a crossed ectopic kidney has been reported only one previous time. A second patient with these findings is the subject of this report."}
{"id": "PMID:197226", "title": "Polyamine metabolism I: Synthesis of dansyl derivatives of N-(monoaminoalkyl)- and N-(polyaminoalkyl)acetamides and elucidation in urine of a cancer patient.", "content": "The dansyl derivatives of N-(monoaminoalkyl)- and N-(polyaminoalkyl)acetamides were synthesized and unequivocally characterized. TLC of the dansyl derivatives obtained from human urine indicated the presence of N-[3-[(4-aminobutyl)amino]propyl]acetamide (N1-acetylspermidine, N-[4-[(3-aminopropyl)amino]butyl]acetamide (N8-acetylspermidine), and N-(4-aminobutyl)acetamide (N-acetylputrescine) in appreciable amounts. The dansyl derivatives of N1-acetylspermidine, N8-acetylspermidine, and N-acetylputrescine were isolated and purified using various chromatographic methods. The mass spectra of these compounds were similar to those of authentic samples, which confirmed the identity of these compounds and established the presence of N8-acetylspermidine as well as N1-acetylspermidine and N-acetylputrescine in human urine.", "contents": "Polyamine metabolism I: Synthesis of dansyl derivatives of N-(monoaminoalkyl)- and N-(polyaminoalkyl)acetamides and elucidation in urine of a cancer patient. The dansyl derivatives of N-(monoaminoalkyl)- and N-(polyaminoalkyl)acetamides were synthesized and unequivocally characterized. TLC of the dansyl derivatives obtained from human urine indicated the presence of N-[3-[(4-aminobutyl)amino]propyl]acetamide (N1-acetylspermidine, N-[4-[(3-aminopropyl)amino]butyl]acetamide (N8-acetylspermidine), and N-(4-aminobutyl)acetamide (N-acetylputrescine) in appreciable amounts. The dansyl derivatives of N1-acetylspermidine, N8-acetylspermidine, and N-acetylputrescine were isolated and purified using various chromatographic methods. The mass spectra of these compounds were similar to those of authentic samples, which confirmed the identity of these compounds and established the presence of N8-acetylspermidine as well as N1-acetylspermidine and N-acetylputrescine in human urine."}
{"id": "PMID:197229", "title": "Single-dose tolerance to morphine hypothermia in the rat: differentiation of acute from long-term tolerance.", "content": "The time course for the development and disappearance fo tolerance to the hypothermic effects of morphine was determined after a single subcutaneous injection (10 mg/kg) in rats. Body temperature responses to second injections, given at varying times after the first, were compared with those produced by the initial injections. Tolerance (attenuation of the hypothermic response) induced by a single dose of morphine was found to be biphasic. Acute tolerance was apparent by 4.5 hours and lasted at least 20 hours after morphine administration. Development of long-term tolerance occurred within 24 hours, was maximal at 3 days and persisted up to 11 days. Both acute and long-term tolerance were drug specific since hypothermic responses to pentobarbital were not altered either 4.5 or 72 hours after morphine. Long-term tolerance was attenuated by co-administration of naloxone with initial dose of morphine. Long-term tolerance induced by multiple doses of morphine (300 mg/kg/day) differed from that induced by a single dose in persistence (3-4 weeks) rather than in quality or magnitude. The thermoregulatory response of the rat provides a sensitive measurement system which allows discrimination between acute and long-term opiate effects.", "contents": "Single-dose tolerance to morphine hypothermia in the rat: differentiation of acute from long-term tolerance. The time course for the development and disappearance fo tolerance to the hypothermic effects of morphine was determined after a single subcutaneous injection (10 mg/kg) in rats. Body temperature responses to second injections, given at varying times after the first, were compared with those produced by the initial injections. Tolerance (attenuation of the hypothermic response) induced by a single dose of morphine was found to be biphasic. Acute tolerance was apparent by 4.5 hours and lasted at least 20 hours after morphine administration. Development of long-term tolerance occurred within 24 hours, was maximal at 3 days and persisted up to 11 days. Both acute and long-term tolerance were drug specific since hypothermic responses to pentobarbital were not altered either 4.5 or 72 hours after morphine. Long-term tolerance was attenuated by co-administration of naloxone with initial dose of morphine. Long-term tolerance induced by multiple doses of morphine (300 mg/kg/day) differed from that induced by a single dose in persistence (3-4 weeks) rather than in quality or magnitude. The thermoregulatory response of the rat provides a sensitive measurement system which allows discrimination between acute and long-term opiate effects."}
{"id": "PMID:197231", "title": "The rapid reduction of disulfiram in blood and plasma.", "content": "A gas chromatographic assay procedure was developed to quantitate the reduction product of disulfiram, diethyldithiocarbamate (DDC), in blood and plasma. The procedure involved the in situ methylation of DDC prior to the extraction and chromatography of the methyl ester. The minimal sensitivity achieved was 0.2 microgram/ml from 1 ml of blood or plasma. The coefficient of variation about any concentration was 10.5%. Calibration curves having a reproducible nonlinear form were prepared up to 9 microgram/ml. The assay procedure was used to evaluate the stability of disulfiram and DDC in blood. Disulfiram was rapidly and quantitatively reduced to DDC within 4 minutes. The DDC thus formed decomposed in human and dog blood with half-lives of 70 and 100 minutes, respectively. The implications of these findings are discussed with respect to the chemical form of disulfiram responsible for the ethanol-sensitizing effect.", "contents": "The rapid reduction of disulfiram in blood and plasma. A gas chromatographic assay procedure was developed to quantitate the reduction product of disulfiram, diethyldithiocarbamate (DDC), in blood and plasma. The procedure involved the in situ methylation of DDC prior to the extraction and chromatography of the methyl ester. The minimal sensitivity achieved was 0.2 microgram/ml from 1 ml of blood or plasma. The coefficient of variation about any concentration was 10.5%. Calibration curves having a reproducible nonlinear form were prepared up to 9 microgram/ml. The assay procedure was used to evaluate the stability of disulfiram and DDC in blood. Disulfiram was rapidly and quantitatively reduced to DDC within 4 minutes. The DDC thus formed decomposed in human and dog blood with half-lives of 70 and 100 minutes, respectively. The implications of these findings are discussed with respect to the chemical form of disulfiram responsible for the ethanol-sensitizing effect."}
{"id": "PMID:197233", "title": "Development of neuromuscular transmission in a larval tunicate.", "content": "1. The time sequence of the development of acetylcholinesterase (AChE), acetylcholine (ACh) receptors and functional synapses on the embryonic muscle membrane in a tunicate larva (Halocynthia roretzi) was investigated in vivo.2. The fertilized tunicate egg was incubated in natural sea water at 9 degrees C. Sixty-eight hr after fertilization the free-swimming larva was hatched, which had six striated muscle fibres in the tail. The developmental stage of the embryo was indicated by the developmental hours after fertilization.3. The transmitter at the neuromuscular junction in the hatched larva is ACh. (i) Neuromuscular transmission was completely blocked by D-tubocurarine (1-5 x 10(-5)M). (ii) Eserine (5-10 x 10(-7)M) approximately doubled the time constant of the falling phase of miniature excitatory junctional currents (e.j.c.s). (iii) The reversal potential of the membrane response to iontophoretically applied ACh was -10 mV and similar to that of e.j.c.s. (iv) AChE was present on the muscle membrane surface.4. AChE activity became visible histochemically on the embryonic cell membrane in the presumptive muscle region as early as the late gastrula stage (27 hr after fertilization, 12 hr before the ACh response appeared).5. The response to iontophoretically applied ACh was present at 39 hr after fertilization but could not be evoked at 38 hr.6. Between 39 and 41 hr after fertilization, the ACh responses increased rapidly, then remained relatively unchanged until larval hatching.7. The stage of the initial appearance of the ACh response corresponded to the stage when the Ca current abruptly increased in the muscle membrane.8. The first sign of neuromuscular transmission was appearance of a giant excitatory junctional potential (e.j.p.) with uniform amplitude (about 15-20 mV) and slow time course (time constant of the falling phase of a giant e.j.c. was 23.4 +/- 6.9 msec, mean and S.D., at -60 mV and 11 degrees C).9. Within a few hours, these giant e.j.p.s disappeared and were successively replaced by medium-sized e.j.p.s and then e.j.p.s similar to those seen in hatched larvae (time constant of the falling phase of a miniature e.j.c. was 8.5 +/- 1.8 msec at -60 mV and 11 degrees C).", "contents": "Development of neuromuscular transmission in a larval tunicate. 1. The time sequence of the development of acetylcholinesterase (AChE), acetylcholine (ACh) receptors and functional synapses on the embryonic muscle membrane in a tunicate larva (Halocynthia roretzi) was investigated in vivo.2. The fertilized tunicate egg was incubated in natural sea water at 9 degrees C. Sixty-eight hr after fertilization the free-swimming larva was hatched, which had six striated muscle fibres in the tail. The developmental stage of the embryo was indicated by the developmental hours after fertilization.3. The transmitter at the neuromuscular junction in the hatched larva is ACh. (i) Neuromuscular transmission was completely blocked by D-tubocurarine (1-5 x 10(-5)M). (ii) Eserine (5-10 x 10(-7)M) approximately doubled the time constant of the falling phase of miniature excitatory junctional currents (e.j.c.s). (iii) The reversal potential of the membrane response to iontophoretically applied ACh was -10 mV and similar to that of e.j.c.s. (iv) AChE was present on the muscle membrane surface.4. AChE activity became visible histochemically on the embryonic cell membrane in the presumptive muscle region as early as the late gastrula stage (27 hr after fertilization, 12 hr before the ACh response appeared).5. The response to iontophoretically applied ACh was present at 39 hr after fertilization but could not be evoked at 38 hr.6. Between 39 and 41 hr after fertilization, the ACh responses increased rapidly, then remained relatively unchanged until larval hatching.7. The stage of the initial appearance of the ACh response corresponded to the stage when the Ca current abruptly increased in the muscle membrane.8. The first sign of neuromuscular transmission was appearance of a giant excitatory junctional potential (e.j.p.) with uniform amplitude (about 15-20 mV) and slow time course (time constant of the falling phase of a giant e.j.c. was 23.4 +/- 6.9 msec, mean and S.D., at -60 mV and 11 degrees C).9. Within a few hours, these giant e.j.p.s disappeared and were successively replaced by medium-sized e.j.p.s and then e.j.p.s similar to those seen in hatched larvae (time constant of the falling phase of a miniature e.j.c. was 8.5 +/- 1.8 msec at -60 mV and 11 degrees C)."}
{"id": "PMID:197234", "title": "Modulation of cyclic nucleotide levels in peripheral nerve without effect on resting or compound action potentials.", "content": "1. Cyclic nucleotide levels and compound action potential magnitudes were measured in frog sciatic nerves following exposure to carbachol, isoprenaline and cyclic nucleotide related substances. 2. The resting cyclic AMP level was 2-4 p-mole/mg protein and the cyclic GMP level was 0-27 p-mole/mg protein in desheathed nerves. 3. Isoprenaline (100 micrometer) caused a twofold increase in cyclic AMP without affecting cyclic GMP levels. Carbachol (100 micrometer) caused a twofold increase in cyclic GMP without affecting cyclic AMP levels. 4. The phosphodiesterase inhibitor theophylline (5 mM) augmented both cyclic AMP and cyclic GMP. 5. The magnitude of the resting or compound action potential was not affected by isoprenaline, carbachol, or phosphodiesterase inhibitors. 6. The cyclic nucleotides and their butyryl derivatives did not affect the magnitude of the resting or compound action potential, either when applied alone or in the presence of a phosphodiesterase inhibitor. 7. In contrast to sympatic tissue we conclude that hormone mediated cyclic nucleotide metabolism in peripheral nerve is unrelated to control of axonal excitability.", "contents": "Modulation of cyclic nucleotide levels in peripheral nerve without effect on resting or compound action potentials. 1. Cyclic nucleotide levels and compound action potential magnitudes were measured in frog sciatic nerves following exposure to carbachol, isoprenaline and cyclic nucleotide related substances. 2. The resting cyclic AMP level was 2-4 p-mole/mg protein and the cyclic GMP level was 0-27 p-mole/mg protein in desheathed nerves. 3. Isoprenaline (100 micrometer) caused a twofold increase in cyclic AMP without affecting cyclic GMP levels. Carbachol (100 micrometer) caused a twofold increase in cyclic GMP without affecting cyclic AMP levels. 4. The phosphodiesterase inhibitor theophylline (5 mM) augmented both cyclic AMP and cyclic GMP. 5. The magnitude of the resting or compound action potential was not affected by isoprenaline, carbachol, or phosphodiesterase inhibitors. 6. The cyclic nucleotides and their butyryl derivatives did not affect the magnitude of the resting or compound action potential, either when applied alone or in the presence of a phosphodiesterase inhibitor. 7. In contrast to sympatic tissue we conclude that hormone mediated cyclic nucleotide metabolism in peripheral nerve is unrelated to control of axonal excitability."}
{"id": "PMID:197235", "title": "Caffeine: its direct and indirect influence on reproduction.", "content": "Caffeine constitutes the active drug principle in a number of commonly consumed beverages. Among North American adults, it holds the distinction as being probably the most widely utilized psychotropic drug. The compound is most often consumed in the form of coffee, which is derived from the bean of the tropical tree Coffea arabica or Coffea robusta. The unique pharmacologic and physiologic properties of caffeine have led to extensive research efforts, especially in the area of mutagenically and teratogenically mediated effects. In this regard, investigators have often overlooked the alterations in catecholamine, free fatty acid and cyclic nucleotide levels that the the presence of caffeine brings about. Such alterations are discussed in light of their effect on reproduction, and an attempt has been made to clarify the effects that the associated habits of alcohol and smoking have on the reproductive system.", "contents": "Caffeine: its direct and indirect influence on reproduction. Caffeine constitutes the active drug principle in a number of commonly consumed beverages. Among North American adults, it holds the distinction as being probably the most widely utilized psychotropic drug. The compound is most often consumed in the form of coffee, which is derived from the bean of the tropical tree Coffea arabica or Coffea robusta. The unique pharmacologic and physiologic properties of caffeine have led to extensive research efforts, especially in the area of mutagenically and teratogenically mediated effects. In this regard, investigators have often overlooked the alterations in catecholamine, free fatty acid and cyclic nucleotide levels that the the presence of caffeine brings about. Such alterations are discussed in light of their effect on reproduction, and an attempt has been made to clarify the effects that the associated habits of alcohol and smoking have on the reproductive system."}
{"id": "PMID:197236", "title": "Fulminant puerperal sepsis associated with aplastic anemia: the case for prophylactic antibiotic therapy.", "content": "Fulminant puerperal sepsis due to Clostridium perfringens occurred in a primiparous 19-year-old woman who developed aplastic anemia during pregnancy. Although the risk of infectious complications among pregnant women with compromised host defenses has not been accurately determined, it appears to be increased, particularly in patients with granulocytopenia. It therefore seems reasonable to give antibiotic prophylaxis during the intrapartum period to immunosuppressed women who come to term. Consideration of the bacterial pathogens most likely to cause acute endometritis in the early puerperium has led us to recommend a short course (72 hours) of penicillin G, 4 million units q4h, and gentamicin, 1,5 mg/kg q8h, as an appropriate regimen for such patients.", "contents": "Fulminant puerperal sepsis associated with aplastic anemia: the case for prophylactic antibiotic therapy. Fulminant puerperal sepsis due to Clostridium perfringens occurred in a primiparous 19-year-old woman who developed aplastic anemia during pregnancy. Although the risk of infectious complications among pregnant women with compromised host defenses has not been accurately determined, it appears to be increased, particularly in patients with granulocytopenia. It therefore seems reasonable to give antibiotic prophylaxis during the intrapartum period to immunosuppressed women who come to term. Consideration of the bacterial pathogens most likely to cause acute endometritis in the early puerperium has led us to recommend a short course (72 hours) of penicillin G, 4 million units q4h, and gentamicin, 1,5 mg/kg q8h, as an appropriate regimen for such patients."}
{"id": "PMID:197237", "title": "3-Hydroxy-17-aralkylmorphinans as potential opiate receptor-site-directed alkylating agents.", "content": "In an effort to develop opiate receptor-site-directed alkylating agents, a series of 3-hydroxy-17-aralkylmorphinans containing reactive groups was synthesized and tested for analgesic and opiate antagonist activity. Many of the target compounds exhibited the characteristics of agonists and, among this group, some were found to be active blockers of morphine analgesia. One of the more potent antagonists (41) was investigated further and it was found that while its action is specifically associated with opiate receptors, 41 could not be classified either as a competitive or noncompetitive antagonist in the classical sense. The duration of antagonist action in vivo of 41 and its in vitro receptor binding characteristics suggest that covalent association with opiate receptors is not not an important factor.", "contents": "3-Hydroxy-17-aralkylmorphinans as potential opiate receptor-site-directed alkylating agents. In an effort to develop opiate receptor-site-directed alkylating agents, a series of 3-hydroxy-17-aralkylmorphinans containing reactive groups was synthesized and tested for analgesic and opiate antagonist activity. Many of the target compounds exhibited the characteristics of agonists and, among this group, some were found to be active blockers of morphine analgesia. One of the more potent antagonists (41) was investigated further and it was found that while its action is specifically associated with opiate receptors, 41 could not be classified either as a competitive or noncompetitive antagonist in the classical sense. The duration of antagonist action in vivo of 41 and its in vitro receptor binding characteristics suggest that covalent association with opiate receptors is not not an important factor."}
{"id": "PMID:197238", "title": "Structure and biological activity of (-)-[3H]dihydroalprenolol, a radioligand for studies of beta-adrenergic receptors.", "content": "(-)-Alprenolol is a potent competitive beta-adrenergic antagonist. \"(-)-[3H]Alprenolol\", a radioactive form of this agent produced by catalytic reduction with tritium, has recently been used successfully as a radioligand for direct studies of beta-adrenergic receptors. In this communication it is documented that the compound formed by catalytic reduction of (-)-alprenolol with tritium gas is the saturated product (-)-[3H]dihydroalprenolol in which tritium is added across the double bond and exchanged into the adjacent benzylic position. No exchange into the aromatic ring was observed. These conclusions were substantiated by results obtained on hydrogenation and deuteration of (-)-alprenolol. The biological activity of (-)-[3H]dihydroalprenolol, dihydroalprenolol, and alprenolol was also shown to be identical as assessed by direct ligand binding and inhibition of catecholamine-stimulated adenylate cyclase.", "contents": "Structure and biological activity of (-)-[3H]dihydroalprenolol, a radioligand for studies of beta-adrenergic receptors. (-)-Alprenolol is a potent competitive beta-adrenergic antagonist. \"(-)-[3H]Alprenolol\", a radioactive form of this agent produced by catalytic reduction with tritium, has recently been used successfully as a radioligand for direct studies of beta-adrenergic receptors. In this communication it is documented that the compound formed by catalytic reduction of (-)-alprenolol with tritium gas is the saturated product (-)-[3H]dihydroalprenolol in which tritium is added across the double bond and exchanged into the adjacent benzylic position. No exchange into the aromatic ring was observed. These conclusions were substantiated by results obtained on hydrogenation and deuteration of (-)-alprenolol. The biological activity of (-)-[3H]dihydroalprenolol, dihydroalprenolol, and alprenolol was also shown to be identical as assessed by direct ligand binding and inhibition of catecholamine-stimulated adenylate cyclase."}
{"id": "PMID:197239", "title": "Techniques for typing Herpesvirus hominis antibody: a comparison of inhibition of peroxidase-labelled antibody staining with inhibition of indirect haemagglutination and with microneutralisation.", "content": "A new technique based upon the inhibition of the peroxidase-labelled antibody staining (PLAS) has been used to type Herpesvirus hominis (HVH) antibodies in four groups of human sera taken from patients with one or both types of HVH infection and in mixtures of different proportions of type 1 and type 2 antisera. The results were compared with those of the microneutralisation (MN) test and the indirect haemagglutination (IHA) inhibition test. The sensitivity and specificity of the three methods were identical for sera containing only one type of HVH antibody. The MN test was slightly more sensitive than the other tests for detecting small amounts of HVH-1 antibody mixed with large amounts of HVH-2 antibody. Nevertheless, the PLAS inhibition technique was far more rapid and it would seem a satisfactory alternative to the IHA inhibition test for HVH antibody typing.", "contents": "Techniques for typing Herpesvirus hominis antibody: a comparison of inhibition of peroxidase-labelled antibody staining with inhibition of indirect haemagglutination and with microneutralisation. A new technique based upon the inhibition of the peroxidase-labelled antibody staining (PLAS) has been used to type Herpesvirus hominis (HVH) antibodies in four groups of human sera taken from patients with one or both types of HVH infection and in mixtures of different proportions of type 1 and type 2 antisera. The results were compared with those of the microneutralisation (MN) test and the indirect haemagglutination (IHA) inhibition test. The sensitivity and specificity of the three methods were identical for sera containing only one type of HVH antibody. The MN test was slightly more sensitive than the other tests for detecting small amounts of HVH-1 antibody mixed with large amounts of HVH-2 antibody. Nevertheless, the PLAS inhibition technique was far more rapid and it would seem a satisfactory alternative to the IHA inhibition test for HVH antibody typing."}
{"id": "PMID:197245", "title": "Seroepidemiologic studies on the possible relationships of human and bovine leukemia: Brief communication.", "content": "A seroepidemiologic study was conducted in an attempt to identify antibodies against the bovine leukemia virus (BLV) in people exposed to cattle with lymphosarcoma. Farm families, farm employees, and veterinarians in contact with cow herds having documented cases of lymphosarcoma were tested for precipitating antibodies to the BLV with the agar gel immunodiffusion test. The cattle also were tested serologically. Information was collected form the farm families regarding consumption of unpasteurized milk from their dairy herd. Twenty-one dairy herds with documented cases of lymphosarcoma were identified. A total of 846 cows from these herds wre bled, of which 33% were serologically positive. No positive sera were found in the 45 dairy farmers, family members, and farm employees associated with the herds with lymphosarcoma. Consumption of raw milk was reported by 77% of the farm group. In addition, 83 veterinarians, 30 leukemia patients, and 200 control human sera were tested and found negative for antibodies to the BLV.", "contents": "Seroepidemiologic studies on the possible relationships of human and bovine leukemia: Brief communication. A seroepidemiologic study was conducted in an attempt to identify antibodies against the bovine leukemia virus (BLV) in people exposed to cattle with lymphosarcoma. Farm families, farm employees, and veterinarians in contact with cow herds having documented cases of lymphosarcoma were tested for precipitating antibodies to the BLV with the agar gel immunodiffusion test. The cattle also were tested serologically. Information was collected form the farm families regarding consumption of unpasteurized milk from their dairy herd. Twenty-one dairy herds with documented cases of lymphosarcoma were identified. A total of 846 cows from these herds wre bled, of which 33% were serologically positive. No positive sera were found in the 45 dairy farmers, family members, and farm employees associated with the herds with lymphosarcoma. Consumption of raw milk was reported by 77% of the farm group. In addition, 83 veterinarians, 30 leukemia patients, and 200 control human sera were tested and found negative for antibodies to the BLV."}
{"id": "PMID:197249", "title": "Dissociation of antiviral and antitumor immunity in resistance to Marek's disease.", "content": "Immunization of chickens either with gluteral-dehyde-inactivated chicken kidney cells infected with Marek's disease (MD) virus or with glutaraldehyde-inactivated cells of MD lymphoma-derived continuous lymphoblastoid cell lines protected against MD. The former type of immunity was associated with an immunologic suppression of virus replication and virus antigen production after challenge with virulent virus, but lymphocytes specifically cytotoxic to cells bearing MD tumor antigens were not detected. In the latter type of immunity, virus multiplication was not affected; some evidence of the stimulation of cell-mediated antitumor immunity was found. The results supported the view that immunity to MD may be directed against either virus-specific or tumor-specific antigens and that in natural resistance to MD both mechanisms may be operative.", "contents": "Dissociation of antiviral and antitumor immunity in resistance to Marek's disease. Immunization of chickens either with gluteral-dehyde-inactivated chicken kidney cells infected with Marek's disease (MD) virus or with glutaraldehyde-inactivated cells of MD lymphoma-derived continuous lymphoblastoid cell lines protected against MD. The former type of immunity was associated with an immunologic suppression of virus replication and virus antigen production after challenge with virulent virus, but lymphocytes specifically cytotoxic to cells bearing MD tumor antigens were not detected. In the latter type of immunity, virus multiplication was not affected; some evidence of the stimulation of cell-mediated antitumor immunity was found. The results supported the view that immunity to MD may be directed against either virus-specific or tumor-specific antigens and that in natural resistance to MD both mechanisms may be operative."}
{"id": "PMID:197250", "title": "Spontaneous regression of Friend virus-induced erythroleukemia. II. regression of Friend murine leukemia virus-induced lymphocytic leukemia.", "content": "We characterized several aspects of spontaneous regression of lymphocytic leukemia in mice. The disease, induced by the helper murine leukemia virus (MuLV) component obtained from the regressing Friend virus complex (RFV), was characterized by spleen and lymph node enlargement, thymus involvement, and anemia. Leukemia regression occurred in about 25% of infected mice and resulted in the return of lymphoid organs to near-normal weight and normal histology and the recovery from anemia. A tenfold to 1,000-fold decrease in virus titer was seen in those mice in which leukemia regressed when compared to leukemic animals, although infectious virus was still recoverable from apparently normal spleens. The sera of mice in which leukemia regressed contained potent virus-neutralizing activity that was associated mainly with immunoglobulins. These studies firmly supported the evidence that the regressing phenotype of RFV was due to its helper MuLV component (MuLV-RF).", "contents": "Spontaneous regression of Friend virus-induced erythroleukemia. II. regression of Friend murine leukemia virus-induced lymphocytic leukemia. We characterized several aspects of spontaneous regression of lymphocytic leukemia in mice. The disease, induced by the helper murine leukemia virus (MuLV) component obtained from the regressing Friend virus complex (RFV), was characterized by spleen and lymph node enlargement, thymus involvement, and anemia. Leukemia regression occurred in about 25% of infected mice and resulted in the return of lymphoid organs to near-normal weight and normal histology and the recovery from anemia. A tenfold to 1,000-fold decrease in virus titer was seen in those mice in which leukemia regressed when compared to leukemic animals, although infectious virus was still recoverable from apparently normal spleens. The sera of mice in which leukemia regressed contained potent virus-neutralizing activity that was associated mainly with immunoglobulins. These studies firmly supported the evidence that the regressing phenotype of RFV was due to its helper MuLV component (MuLV-RF)."}
{"id": "PMID:197252", "title": "Hypocalcemia and nephrogenous cyclic AMP production in critically ill or injured patients.", "content": "Critically ill or injured patients often have impaired cardiovascular function. Since low ionized calcium levels can cause such changes, serum calcium and urine calcium were measured in a prospective study involving 28 criticially ill or injured patients and 16 normal controls. Serum protein levels were also measured to calculate \"corrected\" total calcium levels. Ionized calcium levels are difficult to measure. Since ionic hypocalcemia is thought to increase the \"nephrogenous production\" of cyclic AMP, cyclic AMP levels were measured in the blood and urine of these patients and the \"nephrogenous\" cyclic AMP calculated from the creatinine clearance. The mean total serum calcium in these patients was 7.7 +/- 0.8 mg/dl (S.D.). This was significantly lower (p less than 0.001) than our controls (9.6 +/- 0.6). When corrected for hypoproteinemia, the mean serum calcium (8.7 +/- 0.8) was still significantly lower (p less than 0.005) than control (9.4 +/- 0.5). The mean urine calcium excretion in the patients (56 +/- 66 mg/100 ml G.F.R.) was lower, but not significantly so, than in the controls (84 +/- 44 mg/100 ml G.F.R.). The \"apparent nephrogenous\" cyclic AMP in the study group was 2,731 +/1 1,451 pm/ml/100 ml G.F.R. The nephrogenous cyclic AMP had a negative correlation (r =-0.45) with \"corrected\" total calcium levels. Thus \"total,\" \"corrected\" total, and \"ionized\" calcium levels appear to be reduced in the majority of critically ill or injured patients studied. The clinical implications of these findings and the potential value of serial cyclic AMP determinations in blood and urine will be discussed.", "contents": "Hypocalcemia and nephrogenous cyclic AMP production in critically ill or injured patients. Critically ill or injured patients often have impaired cardiovascular function. Since low ionized calcium levels can cause such changes, serum calcium and urine calcium were measured in a prospective study involving 28 criticially ill or injured patients and 16 normal controls. Serum protein levels were also measured to calculate \"corrected\" total calcium levels. Ionized calcium levels are difficult to measure. Since ionic hypocalcemia is thought to increase the \"nephrogenous production\" of cyclic AMP, cyclic AMP levels were measured in the blood and urine of these patients and the \"nephrogenous\" cyclic AMP calculated from the creatinine clearance. The mean total serum calcium in these patients was 7.7 +/- 0.8 mg/dl (S.D.). This was significantly lower (p less than 0.001) than our controls (9.6 +/- 0.6). When corrected for hypoproteinemia, the mean serum calcium (8.7 +/- 0.8) was still significantly lower (p less than 0.005) than control (9.4 +/- 0.5). The mean urine calcium excretion in the patients (56 +/- 66 mg/100 ml G.F.R.) was lower, but not significantly so, than in the controls (84 +/- 44 mg/100 ml G.F.R.). The \"apparent nephrogenous\" cyclic AMP in the study group was 2,731 +/1 1,451 pm/ml/100 ml G.F.R. The nephrogenous cyclic AMP had a negative correlation (r =-0.45) with \"corrected\" total calcium levels. Thus \"total,\" \"corrected\" total, and \"ionized\" calcium levels appear to be reduced in the majority of critically ill or injured patients studied. The clinical implications of these findings and the potential value of serial cyclic AMP determinations in blood and urine will be discussed."}
{"id": "PMID:197253", "title": "Management of nasopharyngeal angiofibroma.", "content": "Successful surgical treatment of nasopharyngeal angiofibroma requires complete pre-operative evaluation and careful choice of a suitable surgical approach. Experience with 12 patients presenting with this tumor demonstrates the value of polytomography and angiography in evaluation. The use of pre-operative estrogens and temporary vessel ligation has decreased blood loss. The surgical approach is modified depending upon tumor location. A tumor confined to the nasopharynx is removed by a transpalatal approach. Extension into the sinuses or orbit necessitates a sublabial incision or lateral rhinotomy. Pterygo-maxillary tumor may be exposed by extension of the sublabial incision posterior to the maxillary tuberosity. This allows one to push the tumor back into the nasopharynx. Intracranial extension is removed by a combined otolaryngologic-neurosurgical approach.", "contents": "Management of nasopharyngeal angiofibroma. Successful surgical treatment of nasopharyngeal angiofibroma requires complete pre-operative evaluation and careful choice of a suitable surgical approach. Experience with 12 patients presenting with this tumor demonstrates the value of polytomography and angiography in evaluation. The use of pre-operative estrogens and temporary vessel ligation has decreased blood loss. The surgical approach is modified depending upon tumor location. A tumor confined to the nasopharynx is removed by a transpalatal approach. Extension into the sinuses or orbit necessitates a sublabial incision or lateral rhinotomy. Pterygo-maxillary tumor may be exposed by extension of the sublabial incision posterior to the maxillary tuberosity. This allows one to push the tumor back into the nasopharynx. Intracranial extension is removed by a combined otolaryngologic-neurosurgical approach."}
{"id": "PMID:197255", "title": "Pseudotypes of vesicular stomatitis virus with the envelope properties of mammalian and primate retroviruses.", "content": "By employing improved techniques it has been possible to produce and characterize a representative spectrum of mammalian and primate retrovirus pseudotypes of vesicular stomatitis virus (VSV). Selection of appropriate cell lines for both the production and subsequent detection of the VSV pseudotypes has been the most important factor in permitting their demonstration. The host range for penetration of these retrovirus pseudotypes of VSV has been defined and found to differ from that reported for the replication of the corresponding retroviruses. Additionally, retroviruses having an identical host range for replication were distinguishable by differences in their host range for penetration, implying that restriction of replication may be occurring by different mechanisms. Studies of the plaque-forming efficiency of retrovirus pseudotypes of VSV in cell lines nonpermissive for replication of the corresponding retroviruses permitted a distinction to be made between the restriction of replication occurring as a consequence of postpenetration events and that occurring as a consequence of a block of penetration itself. The demonstration of primate retrovirus pseudotypes of VSV permits the use of VSV as a probe for the detection of this group of viruses.", "contents": "Pseudotypes of vesicular stomatitis virus with the envelope properties of mammalian and primate retroviruses. By employing improved techniques it has been possible to produce and characterize a representative spectrum of mammalian and primate retrovirus pseudotypes of vesicular stomatitis virus (VSV). Selection of appropriate cell lines for both the production and subsequent detection of the VSV pseudotypes has been the most important factor in permitting their demonstration. The host range for penetration of these retrovirus pseudotypes of VSV has been defined and found to differ from that reported for the replication of the corresponding retroviruses. Additionally, retroviruses having an identical host range for replication were distinguishable by differences in their host range for penetration, implying that restriction of replication may be occurring by different mechanisms. Studies of the plaque-forming efficiency of retrovirus pseudotypes of VSV in cell lines nonpermissive for replication of the corresponding retroviruses permitted a distinction to be made between the restriction of replication occurring as a consequence of postpenetration events and that occurring as a consequence of a block of penetration itself. The demonstration of primate retrovirus pseudotypes of VSV permits the use of VSV as a probe for the detection of this group of viruses."}
{"id": "PMID:197256", "title": "Cell-free synthesis of herpes simplex virus-coded pyrimidine deoxyribonucleoside kinase enzyme.", "content": "The incubation of a cell-free protein-synthesizing system prepared from rabbit reticulocytes with cytoplasmic RNA from herpes simplex virus (HSV)-infected cells resulted in increased thymidine kinase activity. This enzyme activity was specifically inhibited by anti-HSV antiserum and was relatively unaffected by TTP, an inhibitor of cellular thymidine kinases. Induction of the new activity was prevented by addition of inhibitors of eucaryotic protein synthesis, and no new activity was detected when RNA from cells infected with pyrimidine deoxyribonucleoside kinase-deficient mutants, instead of wild-type HSV, was added. An increased deoxycytidine kinase activity with similar properties to the HSV-specified enzyme activity was also present in cell-free systems incubated with RNA from HSV-infected cells. Phosphorylation of thymidine and deoxycytidine at 30 degrees C continued for longer than 11 h. The findings are consistent with the accurate synthesis in vitro of enzymically active HSV-specified pyrimidine deoxyribonucleoside kinase.", "contents": "Cell-free synthesis of herpes simplex virus-coded pyrimidine deoxyribonucleoside kinase enzyme. The incubation of a cell-free protein-synthesizing system prepared from rabbit reticulocytes with cytoplasmic RNA from herpes simplex virus (HSV)-infected cells resulted in increased thymidine kinase activity. This enzyme activity was specifically inhibited by anti-HSV antiserum and was relatively unaffected by TTP, an inhibitor of cellular thymidine kinases. Induction of the new activity was prevented by addition of inhibitors of eucaryotic protein synthesis, and no new activity was detected when RNA from cells infected with pyrimidine deoxyribonucleoside kinase-deficient mutants, instead of wild-type HSV, was added. An increased deoxycytidine kinase activity with similar properties to the HSV-specified enzyme activity was also present in cell-free systems incubated with RNA from HSV-infected cells. Phosphorylation of thymidine and deoxycytidine at 30 degrees C continued for longer than 11 h. The findings are consistent with the accurate synthesis in vitro of enzymically active HSV-specified pyrimidine deoxyribonucleoside kinase."}
{"id": "PMID:197257", "title": "Effect of helper virus on the number of murine sarcoma virus DNA copies in infected mammalian cells.", "content": "Cell lines of four mammalian species were each examined for the number of Moloney murine sarcoma virus (M-MSV) DNA copies in total cellular DNA after M-MSV transformation. Sarcoma-positive, leukemia-negative (S+L-) M-MSV-transformed cells were compared to M-MSV-transformed cells infected with a replicating leukemia virus. Both unfractionated M-MSV complementary DNA and complementary DNA representing the MSV-specific and the MSV-murine leukemia virus-common regions of the M-MSV genome were hybridized to total cellular DNA of various species. DNAs of mouse, cat, dog, and human S+L-cells contained from less than one to a few proviral M-MSV DNA copies per haploid genome. In contrast, helper virus-coinfected, M-MSV-producing cells of each species showed a 3- to 10-fold increase in M-MSV proviral DNA over that found in corresponding S+L- cells. MSV-specific and MSV-murine leukemia virus-common nucleotide sequences were each increased to a similar degree. A corresponding examination of cellular DNA of leukemia virus-infected normal or S+L- mammalian cells was performed to establish the resulting number of leukemia proviral DNA copies. The infection of normal or S+L- mammalian cells with several leukemia-type viruses that did not have nucleotide sequences closely related to the cell before infection resulted in the appearance of one to three corresponding leukemia proviral DNA copies.", "contents": "Effect of helper virus on the number of murine sarcoma virus DNA copies in infected mammalian cells. Cell lines of four mammalian species were each examined for the number of Moloney murine sarcoma virus (M-MSV) DNA copies in total cellular DNA after M-MSV transformation. Sarcoma-positive, leukemia-negative (S+L-) M-MSV-transformed cells were compared to M-MSV-transformed cells infected with a replicating leukemia virus. Both unfractionated M-MSV complementary DNA and complementary DNA representing the MSV-specific and the MSV-murine leukemia virus-common regions of the M-MSV genome were hybridized to total cellular DNA of various species. DNAs of mouse, cat, dog, and human S+L-cells contained from less than one to a few proviral M-MSV DNA copies per haploid genome. In contrast, helper virus-coinfected, M-MSV-producing cells of each species showed a 3- to 10-fold increase in M-MSV proviral DNA over that found in corresponding S+L- cells. MSV-specific and MSV-murine leukemia virus-common nucleotide sequences were each increased to a similar degree. A corresponding examination of cellular DNA of leukemia virus-infected normal or S+L- mammalian cells was performed to establish the resulting number of leukemia proviral DNA copies. The infection of normal or S+L- mammalian cells with several leukemia-type viruses that did not have nucleotide sequences closely related to the cell before infection resulted in the appearance of one to three corresponding leukemia proviral DNA copies."}
{"id": "PMID:197258", "title": "Clonal transformation of adult human leukocytes by Epstein-Barr virus.", "content": "We have developed a clonal transformation assay for Epstein-Barr virus which uses adult human leukocytes as target cells. The target cells were isolated from Epstein-Barr seronegative donors, and the same donor's cells could be studied repeatedly over long periods of time. When these cells were transformed by Epstein-Barr virus and had proliferated sufficiently to be studied, they had an average cloning efficiency of 3%. Assuming this average cloning efficiency obtains at the onset of transformation, we calculate that transformation by Epstein-Barr virus leads to immortalization maximally of about 1 in 30 of the adult peripheral leukocytes exposed to the virus. Studying the number of colonies transformed as a function of the amount of virus to which the cells are exposed indicates that a single DNA-containing virus particle is sufficient to transform a cell. All of the transformed clones studied harbored viral DNA. This technique will now permit, for the first time, our studying clonal variations in adult peripheral leukocytes transformed by Epstein-Barr virus as a function of input multiplicity of the virus and of the donor's immune status.", "contents": "Clonal transformation of adult human leukocytes by Epstein-Barr virus. We have developed a clonal transformation assay for Epstein-Barr virus which uses adult human leukocytes as target cells. The target cells were isolated from Epstein-Barr seronegative donors, and the same donor's cells could be studied repeatedly over long periods of time. When these cells were transformed by Epstein-Barr virus and had proliferated sufficiently to be studied, they had an average cloning efficiency of 3%. Assuming this average cloning efficiency obtains at the onset of transformation, we calculate that transformation by Epstein-Barr virus leads to immortalization maximally of about 1 in 30 of the adult peripheral leukocytes exposed to the virus. Studying the number of colonies transformed as a function of the amount of virus to which the cells are exposed indicates that a single DNA-containing virus particle is sufficient to transform a cell. All of the transformed clones studied harbored viral DNA. This technique will now permit, for the first time, our studying clonal variations in adult peripheral leukocytes transformed by Epstein-Barr virus as a function of input multiplicity of the virus and of the donor's immune status."}
{"id": "PMID:197259", "title": "Relationship between Moloney murine leukemia and sarcoma virus RNAs: purification and hybridization map of complementary DNAs from defined regions of Moloney murine sarcoma virus 124.", "content": "Complementary DNAs (cDNA's) specific for various regions of the Moloney murine sarcoma virus (MSV) 124 RNA genome were prepared by cross-hybridization techniques. A cDNA specific for the first 1,000 nucleotides adjacent to the RNA 3' end (cDNA 3') was prepared and shown to also be complementary to the 3'-terminal 1,000 nucleotides of a related Moloney murine leukemia virus (MLV) genome. A cDNA complementary to the \"MSV-specific\" portion of the MSV 124 genome was prepared. This cDNA was shown not to anneal to Moloney MLV RNA and to anneal to a portion of the viral RNA of about 1,500 to 1,800 nucleotides in length, located 1,000 nucleotides from the 3' end of MSV RNA. A cDNA common to the genome of MSV and MLV was also obtained and shown to anneal to the 5'-terminal two-thirds, as well as to the 3'-terminal 1,000 nucleotides, of the MSV RNA genome. This cDNA also annealed to the RNA from MLV and mainly to the 5'-terminal half of the MLV genome. It is concluded that the 6-kilobase Moloney MSV 124 RNA genome has a sequence arrangement that includes (i) a 3' portion of about 1,000 nucleotides, which is also present at the 3' terminus of MLV; (ii) an MSV-specific region, not shared with MLV, which extends between 1,000 and 2,500 nucleotides from the 3' terminus; and (iii) a second \"common\" region, again shared with MLV, which extends from 2,500 nucleotides to the 5' terminus. This second common region appears to be located in the 5' half of the 10-kilobase MLV genome as well. Experiments in which a large excess of cold MLV cDNA was annealed to (3)H-labeled polyadenylic acid-containing fragments of MSV RNA gave results consistent with this arrangement of the MSV genome.", "contents": "Relationship between Moloney murine leukemia and sarcoma virus RNAs: purification and hybridization map of complementary DNAs from defined regions of Moloney murine sarcoma virus 124. Complementary DNAs (cDNA's) specific for various regions of the Moloney murine sarcoma virus (MSV) 124 RNA genome were prepared by cross-hybridization techniques. A cDNA specific for the first 1,000 nucleotides adjacent to the RNA 3' end (cDNA 3') was prepared and shown to also be complementary to the 3'-terminal 1,000 nucleotides of a related Moloney murine leukemia virus (MLV) genome. A cDNA complementary to the \"MSV-specific\" portion of the MSV 124 genome was prepared. This cDNA was shown not to anneal to Moloney MLV RNA and to anneal to a portion of the viral RNA of about 1,500 to 1,800 nucleotides in length, located 1,000 nucleotides from the 3' end of MSV RNA. A cDNA common to the genome of MSV and MLV was also obtained and shown to anneal to the 5'-terminal two-thirds, as well as to the 3'-terminal 1,000 nucleotides, of the MSV RNA genome. This cDNA also annealed to the RNA from MLV and mainly to the 5'-terminal half of the MLV genome. It is concluded that the 6-kilobase Moloney MSV 124 RNA genome has a sequence arrangement that includes (i) a 3' portion of about 1,000 nucleotides, which is also present at the 3' terminus of MLV; (ii) an MSV-specific region, not shared with MLV, which extends between 1,000 and 2,500 nucleotides from the 3' terminus; and (iii) a second \"common\" region, again shared with MLV, which extends from 2,500 nucleotides to the 5' terminus. This second common region appears to be located in the 5' half of the 10-kilobase MLV genome as well. Experiments in which a large excess of cold MLV cDNA was annealed to (3)H-labeled polyadenylic acid-containing fragments of MSV RNA gave results consistent with this arrangement of the MSV genome."}
{"id": "PMID:197260", "title": "Integration of proviral DNA in chicken cells infected with Schmidt-Ruppin Rous sarcoma virus is not enhanced by DNA repair.", "content": "The effect DNA repair might have on the integration of exogenous proviral DNA into host cell DNA was investigated by comparing the efficiency of proviral DNA integration in normal chicken embryonic fibroblasts and in chicken embryonic fibroblasts treated with UV or 4-nitroquinoline-1-oxide. The cells were treated with UV or 4-nitroquinoline-1-oxide at various time intervals ranging from 6 h before to 24 h after infection with Schmidt-Ruppin strain A of Rous sarcoma virus. The chicken embryonic fibroblasts were subsequently cultured for 18 to 21 days to ensure maximal integration and elimination of nonintegrated exogenous proviral DNA before DNA was extracted. Integration of proviral DNA into the cellular genome was quantitated by hybridization of denatured cellular DNA on filters with an excess of (3)H-labeled 35S viral RNA. The copy number of the integrated proviruses in normal cells and in infected cells was also determined from the kinetics of liquid RNA-DNA hybridization in DNA excess. Both RNA excess and DNA excess methods of hybridization indicate that two to three copies of the endogenous provirus appear to be present per haploid normal chicken cell genome and that two to three copies of the provirus of Schmidt-Ruppin strain A of Rous sarcoma virus become integrated per haploid cell genome after infection. The copy number of viral genome equivalents integrated per cell treated with UV or 4-nitroquinoline-1-oxide at different time intervals before or after infection did not differ from the copy number in untreated but infected cells. This finding supports our previous report that the integration of oncornavirus proviral DNA is restricted to specific sites in the host cell DNA and suggests a specific mechanism for integration.", "contents": "Integration of proviral DNA in chicken cells infected with Schmidt-Ruppin Rous sarcoma virus is not enhanced by DNA repair. The effect DNA repair might have on the integration of exogenous proviral DNA into host cell DNA was investigated by comparing the efficiency of proviral DNA integration in normal chicken embryonic fibroblasts and in chicken embryonic fibroblasts treated with UV or 4-nitroquinoline-1-oxide. The cells were treated with UV or 4-nitroquinoline-1-oxide at various time intervals ranging from 6 h before to 24 h after infection with Schmidt-Ruppin strain A of Rous sarcoma virus. The chicken embryonic fibroblasts were subsequently cultured for 18 to 21 days to ensure maximal integration and elimination of nonintegrated exogenous proviral DNA before DNA was extracted. Integration of proviral DNA into the cellular genome was quantitated by hybridization of denatured cellular DNA on filters with an excess of (3)H-labeled 35S viral RNA. The copy number of the integrated proviruses in normal cells and in infected cells was also determined from the kinetics of liquid RNA-DNA hybridization in DNA excess. Both RNA excess and DNA excess methods of hybridization indicate that two to three copies of the endogenous provirus appear to be present per haploid normal chicken cell genome and that two to three copies of the provirus of Schmidt-Ruppin strain A of Rous sarcoma virus become integrated per haploid cell genome after infection. The copy number of viral genome equivalents integrated per cell treated with UV or 4-nitroquinoline-1-oxide at different time intervals before or after infection did not differ from the copy number in untreated but infected cells. This finding supports our previous report that the integration of oncornavirus proviral DNA is restricted to specific sites in the host cell DNA and suggests a specific mechanism for integration."}
{"id": "PMID:197261", "title": "Endogenous RD-114 virus genome expression in malignant tissues of domestic cats.", "content": "Endogenous xenotropic cat type C virus (RD-114)- and infectious feline leukemia virus (FeLV)-specific gene expressions were measured in spontaneous sarcomas carcinomas, and nonmalignant cat tissues by molecular hybridization for virus-specific RNA and competition radio-immunoassays for the major internal protein (p30) of these two viruses. The results indicate that RD-114 gene expression in sarcomas and carcinomas at both RNA and p30 levels is significantly higher than histologically normal tissues from cats free of cancer. In contrast, the levels of FeLV viral RNA and p30 are fount to be low or undetectable in the majority of these tumored and normal tissues examined. Whereas variability in the amounts of RD-114 OR FeLV RNA and p30 expressed is found in tissues from different cats, their expression is fairly uniform in multiple malignant tissues of the same cat. The finding of widespread occurrence of elevated RD-114 gene expression in sarcomas and carcinomas is consistent with our similar observation with natural lymphomas of domestic cats and suggests that expression of certain functions of this endogenous virus may be etiologically involved in the development of many different spontaneous neoplasms of cats.", "contents": "Endogenous RD-114 virus genome expression in malignant tissues of domestic cats. Endogenous xenotropic cat type C virus (RD-114)- and infectious feline leukemia virus (FeLV)-specific gene expressions were measured in spontaneous sarcomas carcinomas, and nonmalignant cat tissues by molecular hybridization for virus-specific RNA and competition radio-immunoassays for the major internal protein (p30) of these two viruses. The results indicate that RD-114 gene expression in sarcomas and carcinomas at both RNA and p30 levels is significantly higher than histologically normal tissues from cats free of cancer. In contrast, the levels of FeLV viral RNA and p30 are fount to be low or undetectable in the majority of these tumored and normal tissues examined. Whereas variability in the amounts of RD-114 OR FeLV RNA and p30 expressed is found in tissues from different cats, their expression is fairly uniform in multiple malignant tissues of the same cat. The finding of widespread occurrence of elevated RD-114 gene expression in sarcomas and carcinomas is consistent with our similar observation with natural lymphomas of domestic cats and suggests that expression of certain functions of this endogenous virus may be etiologically involved in the development of many different spontaneous neoplasms of cats."}
{"id": "PMID:197262", "title": "Feline leukemia virus: biochemical and immunological characterization of gag gene-coded structural proteins.", "content": "The major non-glycosylated structural proteins of feline leukemia virus have been isolated, and competition immunoassays have been developed for each. These proteins include the 27,000- to 30,000-molecular-weight major internal antigen designated p30, a 15,000-molecular-weight protein (p15), an acidic protein of 12,000 molecular weight (p12), and a highly basic 10,000-molecular-weight protein (p10). Immunologically and biochemically corresponding proteins of feline and murine leukemia viruses have been identified. and, on the basis of analogy to the known sequence of a prototype type C virus of mouse origin, the map order of the gag region of the feline type C viral genome has been tentatively deduced as NH2-p15-p12-p10-COOH. The demonstration of two feline leukemia virus gag gene-coded proteins, p15 and p12, expressed in the form of an uncleaved precursor in a mink cell line nonproductively transformed  by feline sarcoma virus provides indirect support for the proposed sequence.", "contents": "Feline leukemia virus: biochemical and immunological characterization of gag gene-coded structural proteins. The major non-glycosylated structural proteins of feline leukemia virus have been isolated, and competition immunoassays have been developed for each. These proteins include the 27,000- to 30,000-molecular-weight major internal antigen designated p30, a 15,000-molecular-weight protein (p15), an acidic protein of 12,000 molecular weight (p12), and a highly basic 10,000-molecular-weight protein (p10). Immunologically and biochemically corresponding proteins of feline and murine leukemia viruses have been identified. and, on the basis of analogy to the known sequence of a prototype type C virus of mouse origin, the map order of the gag region of the feline type C viral genome has been tentatively deduced as NH2-p15-p12-p10-COOH. The demonstration of two feline leukemia virus gag gene-coded proteins, p15 and p12, expressed in the form of an uncleaved precursor in a mink cell line nonproductively transformed  by feline sarcoma virus provides indirect support for the proposed sequence."}
{"id": "PMID:197263", "title": "HindIII and Sst I restriction sites mapped on rabbit poxvirus and vaccinia virus DNA.", "content": "The DNAs of two closely related orthopoxviruses, rabbit poxvirus (RPV) and vaccinia virus (VV), were mapped by overlapping-fragment analysis using restriction endonucleases HindIII and Sst I. The exact arrangement of these fragments was accomplished by total digestion of isolated partial restriction products and by end-fragment determination. RPV and VV DNAs showed identical restriction patterns in an internal region comprising approximately 60% of the genome. The size, by electrophoretical analysis of the RPV DNA, was 118 X 10(6) daltons, some 6 X 10(6) daltons less than VV DNA. The two opposite terminal restriction fragments of RPV DNA cross-hybridized to each other.", "contents": "HindIII and Sst I restriction sites mapped on rabbit poxvirus and vaccinia virus DNA. The DNAs of two closely related orthopoxviruses, rabbit poxvirus (RPV) and vaccinia virus (VV), were mapped by overlapping-fragment analysis using restriction endonucleases HindIII and Sst I. The exact arrangement of these fragments was accomplished by total digestion of isolated partial restriction products and by end-fragment determination. RPV and VV DNAs showed identical restriction patterns in an internal region comprising approximately 60% of the genome. The size, by electrophoretical analysis of the RPV DNA, was 118 X 10(6) daltons, some 6 X 10(6) daltons less than VV DNA. The two opposite terminal restriction fragments of RPV DNA cross-hybridized to each other."}
{"id": "PMID:197264", "title": "Differential effect of arabinofuranosylthymine of the replication of human herpesviruses.", "content": "The thymidine analog 1-beta-arabinofuranosylthymine (ara-T) has previously been found to selectively inhibit herpes simplex virus replication. At a relatively nontoxic conentration (50 microgram/ml), ara-T reduced herpes simplex virus yields by 4 to 5 log10. Ara-T was also effective in inhibiting the replication of varicellazoster virus (VZV) in vitro in human embryo fibroblasts, completely preventing VZV-specific cytopathic effects. The inhibition of VZV was reversible upon drug removal at 48 h after addition but was not reversible after 5 days of treatment. ara-T also reduced cell-free virus infectivity and the plaque-forming cell yield of VZV. Compared with the untreated controls, which demonstrated a 1-log10 increase over input plaque-forming cells at 24 h after infection, 50 microgram of ara-T per ml resulted in a 1-log10 decrease. In contrast to herpes simplex virus and VZV, cytomegalovirus replication was relatively resistant to ara-T. Neither cytopathic effects nor the incorporation of [3H]thymidine into acid-insoluble material in cytomegalovirus-infected cells was markedly affected. Analysis of the newly synthesized labeled DNA by CsCl buoyant density determinations indicated that the same relative proportions of cell and virus DNA were synthesized with or without added drug. Interpretation of these results with regard to virus-induced deoxypyrimidine kinase is discussed.", "contents": "Differential effect of arabinofuranosylthymine of the replication of human herpesviruses. The thymidine analog 1-beta-arabinofuranosylthymine (ara-T) has previously been found to selectively inhibit herpes simplex virus replication. At a relatively nontoxic conentration (50 microgram/ml), ara-T reduced herpes simplex virus yields by 4 to 5 log10. Ara-T was also effective in inhibiting the replication of varicellazoster virus (VZV) in vitro in human embryo fibroblasts, completely preventing VZV-specific cytopathic effects. The inhibition of VZV was reversible upon drug removal at 48 h after addition but was not reversible after 5 days of treatment. ara-T also reduced cell-free virus infectivity and the plaque-forming cell yield of VZV. Compared with the untreated controls, which demonstrated a 1-log10 increase over input plaque-forming cells at 24 h after infection, 50 microgram of ara-T per ml resulted in a 1-log10 decrease. In contrast to herpes simplex virus and VZV, cytomegalovirus replication was relatively resistant to ara-T. Neither cytopathic effects nor the incorporation of [3H]thymidine into acid-insoluble material in cytomegalovirus-infected cells was markedly affected. Analysis of the newly synthesized labeled DNA by CsCl buoyant density determinations indicated that the same relative proportions of cell and virus DNA were synthesized with or without added drug. Interpretation of these results with regard to virus-induced deoxypyrimidine kinase is discussed."}
{"id": "PMID:197265", "title": "Viruses of Entamoeba histolytica. VII. Novel beaded virus.", "content": "A third amoebal virus type was isolated from four different strains of Entamoeba histolytica. The virus was most frequently seen as a linear structure about 235 nm long and consisting of 14 beadlike structures about 19 nm in diameter. A \"dimer\" of twice the length and consisting of 28 beads was occationally encountered. The virus replicated in the nucleus, forming ordered arrays. Acridine orange staining of viral aggregates in infected nuclei suggested the presence of double-stranded nucleic acid.", "contents": "Viruses of Entamoeba histolytica. VII. Novel beaded virus. A third amoebal virus type was isolated from four different strains of Entamoeba histolytica. The virus was most frequently seen as a linear structure about 235 nm long and consisting of 14 beadlike structures about 19 nm in diameter. A \"dimer\" of twice the length and consisting of 28 beads was occationally encountered. The virus replicated in the nucleus, forming ordered arrays. Acridine orange staining of viral aggregates in infected nuclei suggested the presence of double-stranded nucleic acid."}
{"id": "PMID:197266", "title": "Simian virus 40-specific ribosome-binding proteins induced by a nondefective adenovirus 2-simian virus 40 hybrid.", "content": "We have studied the intracellular distribution of the two simian virus 40-specific proteins, with apparent molecular weights of 56,000 and 42,000, detectable in human KB cells infected by a nondefective adenovirus 2-simian virus 40 hybrid, Ad2+ND2. After a 20-min pulse of [35S]methionine, about two-thirds of the newly synthesized 56K protein and one-third of the 42K protein were found localized on the plasma membrane. The remainder of each protein was found in the cytoplasm, whereas the nuclear fraction was virtually free of either component. A significant portion of both proteins present in the cytoplasmic fraction was complexed to the 40S ribosomal subunits and was not removed by treatment with 0.5 M KCl. Moreover, the portion that was found free in the cytoplasm could bind preferentially and quantitatively to purified 40S ribosomes in vitro, leading us to propose that these simian virus 40 proteins may act as translational control elements in cells.", "contents": "Simian virus 40-specific ribosome-binding proteins induced by a nondefective adenovirus 2-simian virus 40 hybrid. We have studied the intracellular distribution of the two simian virus 40-specific proteins, with apparent molecular weights of 56,000 and 42,000, detectable in human KB cells infected by a nondefective adenovirus 2-simian virus 40 hybrid, Ad2+ND2. After a 20-min pulse of [35S]methionine, about two-thirds of the newly synthesized 56K protein and one-third of the 42K protein were found localized on the plasma membrane. The remainder of each protein was found in the cytoplasm, whereas the nuclear fraction was virtually free of either component. A significant portion of both proteins present in the cytoplasmic fraction was complexed to the 40S ribosomal subunits and was not removed by treatment with 0.5 M KCl. Moreover, the portion that was found free in the cytoplasm could bind preferentially and quantitatively to purified 40S ribosomes in vitro, leading us to propose that these simian virus 40 proteins may act as translational control elements in cells."}
{"id": "PMID:197267", "title": "Evidence for recombination between N- and B-tropic murine leukemia viruses: analysis of three virion proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.", "content": "We have sodium dodecyl sulfate-polyacrylamide gel electrophoresis to analyze the virion proteins of an N- and a B-tropic C-type virus derived from the BALB/c mouse and 21 putative recombinants, designated XLP-N viruses, obtained from seven crosses between these N- and B-tropic viruses. All the XLP-N viruses are N-tropic but posses the XC plaque morphology of their B-tropic virus parent. Three virion proteins, p15, p30, and gp70, of the parental viruses each differ in electrophoretic mobility. Two recombinants were found that possess a p15 that comigrates with p15 of the B virus; 19 possess a p15 that comigrates with N virus p15. Sixteen recombinants possess a gp70 that migrates like the gp70 of the B virus: four have gp70 with an electrophoretic mobility like that of the N virus gp70. All 21 recombinants possess a p30 that comigrates with p30 of their N virus parent. Given the origin and phenotype of XLP-N viruses, these results would seem to provide good evidence that these viruses are recombinants.", "contents": "Evidence for recombination between N- and B-tropic murine leukemia viruses: analysis of three virion proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We have sodium dodecyl sulfate-polyacrylamide gel electrophoresis to analyze the virion proteins of an N- and a B-tropic C-type virus derived from the BALB/c mouse and 21 putative recombinants, designated XLP-N viruses, obtained from seven crosses between these N- and B-tropic viruses. All the XLP-N viruses are N-tropic but posses the XC plaque morphology of their B-tropic virus parent. Three virion proteins, p15, p30, and gp70, of the parental viruses each differ in electrophoretic mobility. Two recombinants were found that possess a p15 that comigrates with p15 of the B virus; 19 possess a p15 that comigrates with N virus p15. Sixteen recombinants possess a gp70 that migrates like the gp70 of the B virus: four have gp70 with an electrophoretic mobility like that of the N virus gp70. All 21 recombinants possess a p30 that comigrates with p30 of their N virus parent. Given the origin and phenotype of XLP-N viruses, these results would seem to provide good evidence that these viruses are recombinants."}
{"id": "PMID:197268", "title": "In vitro synthesis of a unique RNA species by a T particle of vesicular stomatitis virus.", "content": "A T particle of vesicular stomatitis virus, containing most of the L-gene region, has been isolated. In vitro, these T particles synthesize exclusively a small adenine-rich RNA that is complementary to the T-particle genome. Partial sequence analysis of this small RNA indicates that it is an RNA of unique sequence with a length of approximately 45 nucleotides.", "contents": "In vitro synthesis of a unique RNA species by a T particle of vesicular stomatitis virus. A T particle of vesicular stomatitis virus, containing most of the L-gene region, has been isolated. In vitro, these T particles synthesize exclusively a small adenine-rich RNA that is complementary to the T-particle genome. Partial sequence analysis of this small RNA indicates that it is an RNA of unique sequence with a length of approximately 45 nucleotides."}
{"id": "PMID:197269", "title": "Dissociation of polyoma virus by the chelation of calcium ions found associated with purified virions.", "content": "Analysis of polyoma virions by X-ray fluorometry demonstrated that calcium (Ca2+) was associated with the purified virion. Treatment of purified virions with ethyleneglycol-bis-N,N'-tetraacetic acid (EGTA), which chelates Ca2+, and the reducing agent dithiothreitol caused the virions to dissociate. Electron microscopy revealed that the virions were dissociated to the capsomere level. Incubation of polyoma virions with 150 mM NaCl, 10 mM  EGTA, and 3 mM dithiothreitol was optimum for the dissociation reaction. The pH for the dissociation reaction ranged from 7.5 to 10.5. Cesium chloride density gradient centrifugation indicated that both EGTA and dithiothreitol were necessary for dissociation to occur; neither reagent alone dissociated the virus. The major protein product of the dissociated viral particles sedimented at 12S. Relationships between these experiments and the alkaline carbonate-bicarbonate dissociation of polyoma are discussed.", "contents": "Dissociation of polyoma virus by the chelation of calcium ions found associated with purified virions. Analysis of polyoma virions by X-ray fluorometry demonstrated that calcium (Ca2+) was associated with the purified virion. Treatment of purified virions with ethyleneglycol-bis-N,N'-tetraacetic acid (EGTA), which chelates Ca2+, and the reducing agent dithiothreitol caused the virions to dissociate. Electron microscopy revealed that the virions were dissociated to the capsomere level. Incubation of polyoma virions with 150 mM NaCl, 10 mM  EGTA, and 3 mM dithiothreitol was optimum for the dissociation reaction. The pH for the dissociation reaction ranged from 7.5 to 10.5. Cesium chloride density gradient centrifugation indicated that both EGTA and dithiothreitol were necessary for dissociation to occur; neither reagent alone dissociated the virus. The major protein product of the dissociated viral particles sedimented at 12S. Relationships between these experiments and the alkaline carbonate-bicarbonate dissociation of polyoma are discussed."}
{"id": "PMID:197270", "title": "Synthesis of proteins and glycoproteins in cells infected with human cytomegalovirus.", "content": "In cytomegalovirus-infected cells, the rate of protein synthesis was detected as two peaks. One occurred during the early phase of infection, 0 to 36 h postinfection, and the other occurred during the late phase, after the initiation of viral DNA synthesis. Double-isotopic-label difference analysis demonstrated that host and viral proteins were synthesized simultaneously during both phases. In the early phase, approximately 70 to 90% of the total proteins synthesized were host proteins, whereas approximately 10 to 30% were viral, even at a multiplicity of infection of 20 PFU/cell. Virus-related proteins or glycoproteins were referred to as infected-cell specific (ICS). Two ICS glycoproteins (gp145 and 100) were clearly detectable and were synthesized preferentially in the early phase of infection. Their synthesis was concomitant with stimulation of the protein synthesis rate. In the late phase of infection, approximately 50 to 60% of the total protein synthesis was viral and approximately 40 to 50% was host. The ICS proteins and glycoproteins detected during the late phase of infection were viral structural proteins. Infectious virus was not detectable until 48 to 72 h postinfection. An inhibitor of viral DNA synthesis, phosphonoacetic acid, prevented the appearance of the late-phase ICS proteins and glycoproteins, but there was little or no effect on early ICS glycoprotein synthesis. Radiolabeled ICS proteins and glycoproteins were identified by their relative rates of synthesis, by their different electrophoretic mobilities compared with those of host proteins and host glycoproteins, and by their similar electrophoretic mobilities compared to those of proteins and glycoproteins associated with virions and dense bodies of cytomegalovirus. Structural viral antigens in the infected-cell extracts were removed by immunoprecipitation, using F(ab')(2) fragments of cytomegalovirus-specific antibodies, and identified as described above. The last two criteria were used to identify viral structural ICS proteins and glycoproteins. Although approximately 35 structural proteins were found to be associated with purified virions and dense bodies, the continued synthesis of host cell proteins complicated their identification in infected cells. Nevertheless, seven of the nine structural glycoproteins were identified as ICS glycoproteins.", "contents": "Synthesis of proteins and glycoproteins in cells infected with human cytomegalovirus. In cytomegalovirus-infected cells, the rate of protein synthesis was detected as two peaks. One occurred during the early phase of infection, 0 to 36 h postinfection, and the other occurred during the late phase, after the initiation of viral DNA synthesis. Double-isotopic-label difference analysis demonstrated that host and viral proteins were synthesized simultaneously during both phases. In the early phase, approximately 70 to 90% of the total proteins synthesized were host proteins, whereas approximately 10 to 30% were viral, even at a multiplicity of infection of 20 PFU/cell. Virus-related proteins or glycoproteins were referred to as infected-cell specific (ICS). Two ICS glycoproteins (gp145 and 100) were clearly detectable and were synthesized preferentially in the early phase of infection. Their synthesis was concomitant with stimulation of the protein synthesis rate. In the late phase of infection, approximately 50 to 60% of the total protein synthesis was viral and approximately 40 to 50% was host. The ICS proteins and glycoproteins detected during the late phase of infection were viral structural proteins. Infectious virus was not detectable until 48 to 72 h postinfection. An inhibitor of viral DNA synthesis, phosphonoacetic acid, prevented the appearance of the late-phase ICS proteins and glycoproteins, but there was little or no effect on early ICS glycoprotein synthesis. Radiolabeled ICS proteins and glycoproteins were identified by their relative rates of synthesis, by their different electrophoretic mobilities compared with those of host proteins and host glycoproteins, and by their similar electrophoretic mobilities compared to those of proteins and glycoproteins associated with virions and dense bodies of cytomegalovirus. Structural viral antigens in the infected-cell extracts were removed by immunoprecipitation, using F(ab')(2) fragments of cytomegalovirus-specific antibodies, and identified as described above. The last two criteria were used to identify viral structural ICS proteins and glycoproteins. Although approximately 35 structural proteins were found to be associated with purified virions and dense bodies, the continued synthesis of host cell proteins complicated their identification in infected cells. Nevertheless, seven of the nine structural glycoproteins were identified as ICS glycoproteins."}
{"id": "PMID:197271", "title": "Structural components of the arenavirus Pichinde.", "content": "Purified Pichinde virions grown in monolayers of BHK-21 cells were found to contain three major species of virion proteins as described previously (Ramos et al., J. Virol. 10:661-667, 1972). Two of the proteins were glycosylated (G1, molecular weight = 64,000; G2, molecular weight = 38,000) and were present in similar proportions on the outer surface of the virions. A third protein (N, molecular weight = 66,000) was not glycosylated and, in association with the viral RNA species, was the major protein component of the viral nucleocapsids. An estimate of the approximate number of molecules of these three major proteins per virion was made. Minor amounts of other proteins were also routinely observed in Pichinde virus preparations. None of the three major protein species were phosphorylated to any significant exten, nor did they contain sulfated components. Two virion RNA species (L and S), but no 18S rRNA species, were detected in Pichinde virus preparations obtained from infected BHK-21 cells.", "contents": "Structural components of the arenavirus Pichinde. Purified Pichinde virions grown in monolayers of BHK-21 cells were found to contain three major species of virion proteins as described previously (Ramos et al., J. Virol. 10:661-667, 1972). Two of the proteins were glycosylated (G1, molecular weight = 64,000; G2, molecular weight = 38,000) and were present in similar proportions on the outer surface of the virions. A third protein (N, molecular weight = 66,000) was not glycosylated and, in association with the viral RNA species, was the major protein component of the viral nucleocapsids. An estimate of the approximate number of molecules of these three major proteins per virion was made. Minor amounts of other proteins were also routinely observed in Pichinde virus preparations. None of the three major protein species were phosphorylated to any significant exten, nor did they contain sulfated components. Two virion RNA species (L and S), but no 18S rRNA species, were detected in Pichinde virus preparations obtained from infected BHK-21 cells."}
{"id": "PMID:197272", "title": "Correlation of virus polypeptide structure with attenuation of poliovirus type 1.", "content": "Several avirulent samples of poliovirus type 1 derived in the process attenuating the neurovirulent Mahoney strain show an altered virus capsid polypeptide, VP-1, on polyacrylamide gel electrophoresis of sodium dodecyl sulfate-disrupted virions.", "contents": "Correlation of virus polypeptide structure with attenuation of poliovirus type 1. Several avirulent samples of poliovirus type 1 derived in the process attenuating the neurovirulent Mahoney strain show an altered virus capsid polypeptide, VP-1, on polyacrylamide gel electrophoresis of sodium dodecyl sulfate-disrupted virions."}
{"id": "PMID:197273", "title": "Antibody-independent detection of virus-specific glycoprotein synthesis is oncornavirus-infected cells.", "content": "A method is described for detecting the synthesis of avian and murine oncornavirus-specific glycoproteins without the use of antibodies raised against viral structural proteins. As applied to cells infected with avian tumor virus, the method served to resolve pr90, the precursor of the major envelope glycoprotein. A virus-specific glycoprotein of about 85,000 daltons, which has several properties expected to a precursor to gp69/71, was detected in cells infected with murine leukemia virus.", "contents": "Antibody-independent detection of virus-specific glycoprotein synthesis is oncornavirus-infected cells. A method is described for detecting the synthesis of avian and murine oncornavirus-specific glycoproteins without the use of antibodies raised against viral structural proteins. As applied to cells infected with avian tumor virus, the method served to resolve pr90, the precursor of the major envelope glycoprotein. A virus-specific glycoprotein of about 85,000 daltons, which has several properties expected to a precursor to gp69/71, was detected in cells infected with murine leukemia virus."}
{"id": "PMID:197274", "title": "Analysis of polyoma virus DNA replicative intermediates by agarose gel electrophoresis.", "content": "Agarose gel electrophoresis has been used to fractionate polyoma virus DNA replicative intermediates (RI) according to maturity. Approximate electrophoretic mobility versus maturity relationships were obtained for both intact (supercoiled) and nicked (relaxed) RI. There was considerable overlap between the supercoiled and relaxed RI populations after electrophoretic fractionation. Intact RI could be recovered from preparative agarose gels for further analysis by centrifugation, electron microscopy, re-electrophoresis, or nuclease digestion.", "contents": "Analysis of polyoma virus DNA replicative intermediates by agarose gel electrophoresis. Agarose gel electrophoresis has been used to fractionate polyoma virus DNA replicative intermediates (RI) according to maturity. Approximate electrophoretic mobility versus maturity relationships were obtained for both intact (supercoiled) and nicked (relaxed) RI. There was considerable overlap between the supercoiled and relaxed RI populations after electrophoretic fractionation. Intact RI could be recovered from preparative agarose gels for further analysis by centrifugation, electron microscopy, re-electrophoresis, or nuclease digestion."}
{"id": "PMID:197275", "title": "Genetics of resistance to phosphonoacetic acid in strain KOS of herpes simplex virus type 1.", "content": "A DNA- temperature-sensitive mutant of herpes simplex virus type 1 exhibiting thermolabile DNA polymerase activity, tsD9, was shown to be resistant to phosphonoacetic acid (PAA) when plated at the permissive temperature. ts+ revertants of tsD9 were PAA sensitive and exhibited DNA polymerase activity intermediate between that of the wild-type virus and tsD9, indicating that both temperature sensitivity and sensitivity to PAA are controlled by the same gene. Since the position of tsD9 on the existing herpes simplex virus type 1 linkage map is known, the locus for PAA resistance--and therefore for the structural gene for viral DNA polymerase--has been identified.", "contents": "Genetics of resistance to phosphonoacetic acid in strain KOS of herpes simplex virus type 1. A DNA- temperature-sensitive mutant of herpes simplex virus type 1 exhibiting thermolabile DNA polymerase activity, tsD9, was shown to be resistant to phosphonoacetic acid (PAA) when plated at the permissive temperature. ts+ revertants of tsD9 were PAA sensitive and exhibited DNA polymerase activity intermediate between that of the wild-type virus and tsD9, indicating that both temperature sensitivity and sensitivity to PAA are controlled by the same gene. Since the position of tsD9 on the existing herpes simplex virus type 1 linkage map is known, the locus for PAA resistance--and therefore for the structural gene for viral DNA polymerase--has been identified."}
{"id": "PMID:197276", "title": "Amebiasis. An increasing problem among homosexuals in New York City.", "content": "During a five-year period at The New York Hospital, Entamoeba histolytica was identified in the stools of 20 men who had not traveled outside the New York area. All of the patients were found subsequently to homosexual. During this same period amebiasis was diagnosed in 30 men who had traveled; only two were homosexual. Of ten patients with E histolytica infection seen during the first year of this study, none were homosexual whereas eight of 11 patients in the fifth year were homosexual, suggesting a gradual increase during this period of this disease in the homosexual community.", "contents": "Amebiasis. An increasing problem among homosexuals in New York City. During a five-year period at The New York Hospital, Entamoeba histolytica was identified in the stools of 20 men who had not traveled outside the New York area. All of the patients were found subsequently to homosexual. During this same period amebiasis was diagnosed in 30 men who had traveled; only two were homosexual. Of ten patients with E histolytica infection seen during the first year of this study, none were homosexual whereas eight of 11 patients in the fifth year were homosexual, suggesting a gradual increase during this period of this disease in the homosexual community."}
{"id": "PMID:197277", "title": "Venereal transmission of enteric pathogens in male homosexuals. Two case reports.", "content": "In two cases there was simultaneous or sequential occurrence of amebiasis, shigellosis, and giardiasis in male homosexuals. Enteric pathogens may, under the proper conditions, be venereally transmitted. In particular, the sexual practices of male homosexuals, most significantly, oral-anal contact, appear to provide the necesseary link for transmission. Evidence suggests that this is a growing problem.", "contents": "Venereal transmission of enteric pathogens in male homosexuals. Two case reports. In two cases there was simultaneous or sequential occurrence of amebiasis, shigellosis, and giardiasis in male homosexuals. Enteric pathogens may, under the proper conditions, be venereally transmitted. In particular, the sexual practices of male homosexuals, most significantly, oral-anal contact, appear to provide the necesseary link for transmission. Evidence suggests that this is a growing problem."}
{"id": "PMID:197278", "title": "Scintigraphic evaluation of suspected acute myocardial infarction.", "content": "Ninety-one patients with chest pain suggestive of acute myocardial infarction were studied by static technetium Tc 99m stannous pyrophosphate scintigraphy and dynamic sodium pertechnetate Tc 99m cardioangiography. Twenty-three of 26 patients (88%) with acute transmural infarcts and 12 of 17 patients (71%) with nontransmural infarcts had abnormal static studies. In 45 patients with negative scintigrams, ECG or serum enzyme changes consistent with acute infarction failed to develop. Three false-positive static studies (6%) were recorded. Twenty of 43 (47%) patients with acute infarction had hemodynamic or structural abnormalities identified by cardioangiography. The dynamic study also proved helpful in localizing the site of infarction and in ruling out certain causes of false-positive static scintigrams.", "contents": "Scintigraphic evaluation of suspected acute myocardial infarction. Ninety-one patients with chest pain suggestive of acute myocardial infarction were studied by static technetium Tc 99m stannous pyrophosphate scintigraphy and dynamic sodium pertechnetate Tc 99m cardioangiography. Twenty-three of 26 patients (88%) with acute transmural infarcts and 12 of 17 patients (71%) with nontransmural infarcts had abnormal static studies. In 45 patients with negative scintigrams, ECG or serum enzyme changes consistent with acute infarction failed to develop. Three false-positive static studies (6%) were recorded. Twenty of 43 (47%) patients with acute infarction had hemodynamic or structural abnormalities identified by cardioangiography. The dynamic study also proved helpful in localizing the site of infarction and in ruling out certain causes of false-positive static scintigrams."}
{"id": "PMID:197279", "title": "Venereal causes of cytomegalovirus mononucleosis.", "content": "Cytomegalovirus (CMV) mononucleosis developed in two men after sexual contact with a woman who had had a similar but medically unverified illness several months before. The CMV was cultured from the woman's urine and cervix. Evidence of recent infection with CMV was also found in a new sexual contact of one of the men. However, roommates of the infected patients remained well, and serologic evidence of CMV infection failed to develop. This small outbreak suggests that CMV may be acquired as a venereal infection that sometimes progresses to the mononucleosis syndrome.", "contents": "Venereal causes of cytomegalovirus mononucleosis. Cytomegalovirus (CMV) mononucleosis developed in two men after sexual contact with a woman who had had a similar but medically unverified illness several months before. The CMV was cultured from the woman's urine and cervix. Evidence of recent infection with CMV was also found in a new sexual contact of one of the men. However, roommates of the infected patients remained well, and serologic evidence of CMV infection failed to develop. This small outbreak suggests that CMV may be acquired as a venereal infection that sometimes progresses to the mononucleosis syndrome."}
{"id": "PMID:197287", "title": "[Types of hyperlipoproteinemia in young persons with ischemic heart diseases engaged in strenuous mental work].", "content": "The results subsequent to an examination of 250 males aged 30-47 suffering from ischemic heart disease and doing strenous mental work are presented. Two variants were used in phenotyping: the first was based on not too high criteria for the cholesterol and triglycerides level (250 and 140 mg%, respectively), the second one having as a groundwork upper limits of the normal value estimated by the authors (250 and 190 mg%, respectively). It was found that, depending upon the actual value of the upper normal limit for triglycerides hyperlipidemia is demonstrable in 64 or 56% of the males. Of most frequent occurrence were the II and IV types of hyperlipoproteinemia with the latter type prevailing in both variants. Most patients with ischemic heart disease demonstrated a fall of alpha-lipoproteins, as ascertained by their separation through disc-electrophoresis in polyacrylamide gel.", "contents": "[Types of hyperlipoproteinemia in young persons with ischemic heart diseases engaged in strenuous mental work]. The results subsequent to an examination of 250 males aged 30-47 suffering from ischemic heart disease and doing strenous mental work are presented. Two variants were used in phenotyping: the first was based on not too high criteria for the cholesterol and triglycerides level (250 and 140 mg%, respectively), the second one having as a groundwork upper limits of the normal value estimated by the authors (250 and 190 mg%, respectively). It was found that, depending upon the actual value of the upper normal limit for triglycerides hyperlipidemia is demonstrable in 64 or 56% of the males. Of most frequent occurrence were the II and IV types of hyperlipoproteinemia with the latter type prevailing in both variants. Most patients with ischemic heart disease demonstrated a fall of alpha-lipoproteins, as ascertained by their separation through disc-electrophoresis in polyacrylamide gel."}
{"id": "PMID:197288", "title": "[Blood viscosity in ischemic heart disease with different types of hyperlipoproteinemia].", "content": "Fifty patients with chronic forms of ischaemic heart disease were examined, their blood viscosity being determined with the aid of a rotational viscosimeter, and their hematocrit and fibrinogen levels being measured. Some increase in blood viscosity was found in patients with ischaemic heart disease with a tension shift of 0.7 and 0.5 dyn/cm2. In analysing the interrelationship between the blood viscosity figures and the risk factors inherent in ischaemic heart disease it was found that smoking results in an increasing blood viscosity with low tension shifts. The highest blood viscosity with low tension shifts. The highest blood viscosity values were found in patients with IIb and IV types of hyperlipoproteinemia. A direct correlation was established between the level of triglycerides and blood viscosity with a tension shift of 0.7 dyn/cm2.", "contents": "[Blood viscosity in ischemic heart disease with different types of hyperlipoproteinemia]. Fifty patients with chronic forms of ischaemic heart disease were examined, their blood viscosity being determined with the aid of a rotational viscosimeter, and their hematocrit and fibrinogen levels being measured. Some increase in blood viscosity was found in patients with ischaemic heart disease with a tension shift of 0.7 and 0.5 dyn/cm2. In analysing the interrelationship between the blood viscosity figures and the risk factors inherent in ischaemic heart disease it was found that smoking results in an increasing blood viscosity with low tension shifts. The highest blood viscosity with low tension shifts. The highest blood viscosity values were found in patients with IIb and IV types of hyperlipoproteinemia. A direct correlation was established between the level of triglycerides and blood viscosity with a tension shift of 0.7 dyn/cm2."}
{"id": "PMID:197289", "title": "[Lipid content in the blood serum of students under nervous-emotional stress].", "content": "Some aspects of the lipids metabolism in the blood serum of students differing in their age, working and learning experience prior to entering the institute, followed up throughout the examination period, are presented. Subject to determination was concentration of total lipids and their principal fractions: phospholipids, free and estherified cholesterol, free fatty acids and triglycerides, accomplished by means of micro-thin layer chromatography. Investigations were conducted 5 weeks, 1-2 days before examination and 5 weeks thereafter. A study of the lipids metabolism under nervous-emotional stress in dynamics may serve as one of the methodological approaches enabling one to reveal in good time any changes in the lipids metabolism.", "contents": "[Lipid content in the blood serum of students under nervous-emotional stress]. Some aspects of the lipids metabolism in the blood serum of students differing in their age, working and learning experience prior to entering the institute, followed up throughout the examination period, are presented. Subject to determination was concentration of total lipids and their principal fractions: phospholipids, free and estherified cholesterol, free fatty acids and triglycerides, accomplished by means of micro-thin layer chromatography. Investigations were conducted 5 weeks, 1-2 days before examination and 5 weeks thereafter. A study of the lipids metabolism under nervous-emotional stress in dynamics may serve as one of the methodological approaches enabling one to reveal in good time any changes in the lipids metabolism."}
{"id": "PMID:197295", "title": "[Herpes simplex of the lid margin (author's transl)].", "content": "Isolated herpes simplex affecting the lid margin can be distinguished from herpes simplex involving the entire eyelid by characteristic features. The typical intermarginal form of herpes-simplex-blepharitis presents itself as an erosion of about 3 mm in length which may be well discerned in detail after fluorescein staining. The skin adjecent to the lesion may also exhibit superficial ulceration, possibly being covered by crusts. The affected portion of the lid shows localized and moderate swelling as well as pain upon pressure. Injection of the bulbar conjunctiva will characteristically be noted mainly in the area opposing the lid lesion. The regional lymph nodes are enlarged, and possibly tender upon palpation. Local medication with anti-viral ophthalmic ointment is effective within a few days.", "contents": "[Herpes simplex of the lid margin (author's transl)]. Isolated herpes simplex affecting the lid margin can be distinguished from herpes simplex involving the entire eyelid by characteristic features. The typical intermarginal form of herpes-simplex-blepharitis presents itself as an erosion of about 3 mm in length which may be well discerned in detail after fluorescein staining. The skin adjecent to the lesion may also exhibit superficial ulceration, possibly being covered by crusts. The affected portion of the lid shows localized and moderate swelling as well as pain upon pressure. Injection of the bulbar conjunctiva will characteristically be noted mainly in the area opposing the lid lesion. The regional lymph nodes are enlarged, and possibly tender upon palpation. Local medication with anti-viral ophthalmic ointment is effective within a few days."}
{"id": "PMID:197296", "title": "[From acupuncture to iris diagnosis (author's transl)].", "content": "Scientific medicine is always encircled by a miscellany of medical fantasies, which come and go, and which offer a short-cut to diagnosis and treatment, and (very occasionally) both together. Oculodiagnosis, or Iridodiagnosis, has little place in honset ophthalmology, but still holds its devotees.", "contents": "[From acupuncture to iris diagnosis (author's transl)]. Scientific medicine is always encircled by a miscellany of medical fantasies, which come and go, and which offer a short-cut to diagnosis and treatment, and (very occasionally) both together. Oculodiagnosis, or Iridodiagnosis, has little place in honset ophthalmology, but still holds its devotees."}
{"id": "PMID:197299", "title": "beta-adrenergic receptor coupled-adenylate cyclase of human fat cell ghosts.", "content": "The effects of beta-adrenergic agonists such as isoproterenol, norepinephrine and epinephrine upon the adenylate cyclase activity of human fat cell ghosts were tested, each alone and in combination with the beta-blocking agent propranolol. Saturating concentrations of these agents showed a 2-6.5-fold increase of enzyme activity without addition of any artificial cofactors. Isoproterenol was more potent in stimulating the enzyme system than epinephrine and nor-epinephrine. Propranolol caused a dose-dependent rightward shift of the log-dose response curve of these beta-adrenergic agonists. The assay of human fat cell adenylate cyclase in vitro may provide a simple anc convenient assay system for the screening of beta-adrenergic drugs of potential therapeutic importance.", "contents": "beta-adrenergic receptor coupled-adenylate cyclase of human fat cell ghosts. The effects of beta-adrenergic agonists such as isoproterenol, norepinephrine and epinephrine upon the adenylate cyclase activity of human fat cell ghosts were tested, each alone and in combination with the beta-blocking agent propranolol. Saturating concentrations of these agents showed a 2-6.5-fold increase of enzyme activity without addition of any artificial cofactors. Isoproterenol was more potent in stimulating the enzyme system than epinephrine and nor-epinephrine. Propranolol caused a dose-dependent rightward shift of the log-dose response curve of these beta-adrenergic agonists. The assay of human fat cell adenylate cyclase in vitro may provide a simple anc convenient assay system for the screening of beta-adrenergic drugs of potential therapeutic importance."}
{"id": "PMID:197298", "title": "[Studies on the structure and metabolism of lipoprotein-X (LP-X), the abnormal plasmalipoprotein in cholestasis (author's transl)].", "content": "Recent results regarding the pathophysiology of hyperlipoproteinemia in cholestasis are reported. The isolation of an abnormal lipoprotein (Lipoprotein-X; LP-X) from the plasma of cholestatic patients was achieved by a combination of various physico-chemical techniques. Most of the plasmacholesterol in these patients is transported in form of this abnormal lipoprotein which is very rich in phospholipids and unesterfied cholesterol. LP-X represents a vesicle with a mean diameter of 700 A. Albumin takes part as a structural protein of the particle. Besides albumin, which seems to be located in an internal water compartment or to be covered with lipids. Apo-C and Apo-D are present as surface proteins. The lack of Apo-B in LP-X, the major apoprotein of normal low density lipoproteins, seems to be the reason for a disturbed endogenous feedback mechanism of hepatic cholesterol synthesis, which is strongly increased in cholestasis. The high specificity and power of the LP-X test as clinical-chemical parameter to demonstrate or exclude cholestasis finds its explanation in our knowledge about the origin of this abnormal lipoprotein in cholestasis. LP-X is formed when a lipoprotein normally excreted with the bile refluxes into the plasma stream to convert into LP-X. This formation depends only on certain physico-chemical requirements and is independent of an energy-providing or enzymatically regulated process. The biological halflife of LP-X is similar to that of normal plasmalipoproteins. However, enzymes of postheparin plasma as well as the lecithin: cholesterol acyltransferase do not seem to play a major role in the catabolism of lipoprotein-X, but only change some of the physicochemical characteristics of this vesicle.", "contents": "[Studies on the structure and metabolism of lipoprotein-X (LP-X), the abnormal plasmalipoprotein in cholestasis (author's transl)]. Recent results regarding the pathophysiology of hyperlipoproteinemia in cholestasis are reported. The isolation of an abnormal lipoprotein (Lipoprotein-X; LP-X) from the plasma of cholestatic patients was achieved by a combination of various physico-chemical techniques. Most of the plasmacholesterol in these patients is transported in form of this abnormal lipoprotein which is very rich in phospholipids and unesterfied cholesterol. LP-X represents a vesicle with a mean diameter of 700 A. Albumin takes part as a structural protein of the particle. Besides albumin, which seems to be located in an internal water compartment or to be covered with lipids. Apo-C and Apo-D are present as surface proteins. The lack of Apo-B in LP-X, the major apoprotein of normal low density lipoproteins, seems to be the reason for a disturbed endogenous feedback mechanism of hepatic cholesterol synthesis, which is strongly increased in cholestasis. The high specificity and power of the LP-X test as clinical-chemical parameter to demonstrate or exclude cholestasis finds its explanation in our knowledge about the origin of this abnormal lipoprotein in cholestasis. LP-X is formed when a lipoprotein normally excreted with the bile refluxes into the plasma stream to convert into LP-X. This formation depends only on certain physico-chemical requirements and is independent of an energy-providing or enzymatically regulated process. The biological halflife of LP-X is similar to that of normal plasmalipoproteins. However, enzymes of postheparin plasma as well as the lecithin: cholesterol acyltransferase do not seem to play a major role in the catabolism of lipoprotein-X, but only change some of the physicochemical characteristics of this vesicle."}
{"id": "PMID:197300", "title": "Inhibition by somatostatin of adenosine-3',5'-monophosphate stimulated hepatic ribosomal protein synthesis.", "content": "Somatostatin which inhibits the secretion of various pituitary and intestinal hormones has been suspected to exert these effects by inhibiting adenosine-3',5'-monophosphate accumulation in the respective endocrine gland. Our results, obtained by cell free protein synthesis and by sedimentation through sucrose gradients of ribosomes, prepared from rat liver after incubation with cyclic AMP and/or somatostatin also suggest this antagonism between somatostatin and cyclic AMP. In addition, they indicate that this antagonism is not restricted to endocrine tissues.", "contents": "Inhibition by somatostatin of adenosine-3',5'-monophosphate stimulated hepatic ribosomal protein synthesis. Somatostatin which inhibits the secretion of various pituitary and intestinal hormones has been suspected to exert these effects by inhibiting adenosine-3',5'-monophosphate accumulation in the respective endocrine gland. Our results, obtained by cell free protein synthesis and by sedimentation through sucrose gradients of ribosomes, prepared from rat liver after incubation with cyclic AMP and/or somatostatin also suggest this antagonism between somatostatin and cyclic AMP. In addition, they indicate that this antagonism is not restricted to endocrine tissues."}
{"id": "PMID:197301", "title": "Nerve excitability: transition from descriptive phenomenology to chemical analysis of mechanisms.", "content": "The electrical activity by which impulses are conducted along nerve and muscle fibers, is carried by Na-and K-ions moving across the excitable membranes due to increased ion permeability. -- A biochemical approach, initiated to elucidate the mechanism of the permeability changes, centered around the analysis of the properties and functions of the proteins, including enzymes, directly associated with the role of AcCh, in the excitable membrane. The results necessitated a fundamentally reformed concept of the role of AcCh. The four proteins specifically associated with the function of AcCh form a cycle which controls the rapid ion permeability changes of the membrane and permits the ion fluxes through dynamic gateways. A model has been elaborated that integrates biochemical, biophysical, and thermodynamic data; it permits the interpretation of many electrophysiological data in molecular terms. AcCh has basically the same function in conducting and synaptic parts of excitable membranes. The new concept has replaced the purely descriptive phenomenology of nerve impulse propagation by the analysis of the chemical mechanisms of nerve excitability and bioelectricity.", "contents": "Nerve excitability: transition from descriptive phenomenology to chemical analysis of mechanisms. The electrical activity by which impulses are conducted along nerve and muscle fibers, is carried by Na-and K-ions moving across the excitable membranes due to increased ion permeability. -- A biochemical approach, initiated to elucidate the mechanism of the permeability changes, centered around the analysis of the properties and functions of the proteins, including enzymes, directly associated with the role of AcCh, in the excitable membrane. The results necessitated a fundamentally reformed concept of the role of AcCh. The four proteins specifically associated with the function of AcCh form a cycle which controls the rapid ion permeability changes of the membrane and permits the ion fluxes through dynamic gateways. A model has been elaborated that integrates biochemical, biophysical, and thermodynamic data; it permits the interpretation of many electrophysiological data in molecular terms. AcCh has basically the same function in conducting and synaptic parts of excitable membranes. The new concept has replaced the purely descriptive phenomenology of nerve impulse propagation by the analysis of the chemical mechanisms of nerve excitability and bioelectricity."}
{"id": "PMID:197302", "title": "The procoagulant activity of human granulocytes, lymphocytes and monocytes stimulated by endotoxin. Coagulation and electron microscopic studies.", "content": "Leukocytes from donor blood were separated by ficoll/Urovison density centrifugation into granulocytes, lymphocytes and monocytes. The cell fractions were suspended in a culture medium to which endotoxin of Salmonella enteritidis was added at a final concentration of 10 microgram/ml. Endotoxin-stimulated monocytes developed a very high tissue factor (thromboplastin) activity while in granulocytes an only negligible amount of tissue factor activity was detectable. The tissue factor activity measured in the preparation of the lymphocytes can be explained by contamination with monocytes. Eelectron microscopic studies showed the lysosomes of all monocytes to be enlarged and activated. Only a fraction of the granulocytes appeared degranulated with prominent vacuoles containing inclusion bodies. Possibly the high tissue factor activity of the monocytes triggers the development of the disseminated intravascular coagulation in the Shwartzman phenomenon.", "contents": "The procoagulant activity of human granulocytes, lymphocytes and monocytes stimulated by endotoxin. Coagulation and electron microscopic studies. Leukocytes from donor blood were separated by ficoll/Urovison density centrifugation into granulocytes, lymphocytes and monocytes. The cell fractions were suspended in a culture medium to which endotoxin of Salmonella enteritidis was added at a final concentration of 10 microgram/ml. Endotoxin-stimulated monocytes developed a very high tissue factor (thromboplastin) activity while in granulocytes an only negligible amount of tissue factor activity was detectable. The tissue factor activity measured in the preparation of the lymphocytes can be explained by contamination with monocytes. Eelectron microscopic studies showed the lysosomes of all monocytes to be enlarged and activated. Only a fraction of the granulocytes appeared degranulated with prominent vacuoles containing inclusion bodies. Possibly the high tissue factor activity of the monocytes triggers the development of the disseminated intravascular coagulation in the Shwartzman phenomenon."}
{"id": "PMID:197311", "title": "The stereology of pulmonary alveolar macrophages after prolonged experimental exposure to tobacco smoke.", "content": "Morphometric analysis was performed on alveolar macrophages obtained by bronchopulmonary lavage of rats exposed to tobacco smoke for periods up to 60 consecutive days. Smoke dosage levels were adjusted so as to be comparable to those of human smokers. Size distributions were obtained for the lavaged macrophage populations of treated and age-matched control animals following 30 and 60 days of smoke exposure. Electron microscopic stereology was used to quantitate alterations in the ultrastructure of the same macrophage preparations. Several significant changes were observed in macrophage morphology following exposure to tobacco smoke, with an estimated mean cell volume more than twice that of controls following 60 days of smoking. After 30 and 60 days of exposure there was a 10- and 16-fold increase, respectively, in the volume density of cytoplasmic lipid inclusions. The surface to volume ratio of the cells and the lysosomal volume density were reduced in macrophages from smoke-exposed animals. A possible relationship between the incidence of lysosomes and the accumulation of cytoplasmic lipid in treated cells is discussed.", "contents": "The stereology of pulmonary alveolar macrophages after prolonged experimental exposure to tobacco smoke. Morphometric analysis was performed on alveolar macrophages obtained by bronchopulmonary lavage of rats exposed to tobacco smoke for periods up to 60 consecutive days. Smoke dosage levels were adjusted so as to be comparable to those of human smokers. Size distributions were obtained for the lavaged macrophage populations of treated and age-matched control animals following 30 and 60 days of smoke exposure. Electron microscopic stereology was used to quantitate alterations in the ultrastructure of the same macrophage preparations. Several significant changes were observed in macrophage morphology following exposure to tobacco smoke, with an estimated mean cell volume more than twice that of controls following 60 days of smoking. After 30 and 60 days of exposure there was a 10- and 16-fold increase, respectively, in the volume density of cytoplasmic lipid inclusions. The surface to volume ratio of the cells and the lysosomal volume density were reduced in macrophages from smoke-exposed animals. A possible relationship between the incidence of lysosomes and the accumulation of cytoplasmic lipid in treated cells is discussed."}
{"id": "PMID:197315", "title": "Cell shape and hexose transport in normal and virus-transformed cells in culture.", "content": "The rate of hexose transport was compared in normal and virus-transformed cells on a monolayer and in suspension. It was shown that: 1) Both trypsin-removed cells and those suspended for an additional day in methyl cellulose had decreased rates of transport and lower available water space when compared with cells on a monolayer. Thus, cell shape affects the overall rate of hexose transport, especially at higher sugar concentrations. 2) Even in suspension, the initial transport rates remained higher in transformed cells with reference to normal cells. Scanning electron micrographs of normal and transformed chick cells revealed morphological differences only in the flat state. This indicates that the increased rate of hexose transport after transformation is not due to a difference in the shape of these cells on a monolayer.", "contents": "Cell shape and hexose transport in normal and virus-transformed cells in culture. The rate of hexose transport was compared in normal and virus-transformed cells on a monolayer and in suspension. It was shown that: 1) Both trypsin-removed cells and those suspended for an additional day in methyl cellulose had decreased rates of transport and lower available water space when compared with cells on a monolayer. Thus, cell shape affects the overall rate of hexose transport, especially at higher sugar concentrations. 2) Even in suspension, the initial transport rates remained higher in transformed cells with reference to normal cells. Scanning electron micrographs of normal and transformed chick cells revealed morphological differences only in the flat state. This indicates that the increased rate of hexose transport after transformation is not due to a difference in the shape of these cells on a monolayer."}
{"id": "PMID:197318", "title": "Isolation of the alanine carrier from the membranes of a thermophilic bacterium and its reconstitution into vesicles capable of transport.", "content": "A carrier protein mediating alanine transport was purified from the membranes of the thermophilic bacterium PS3, by ion exchange chromatography in the presence of both Triton X-100 and urea. The alanine carrier was recovered in the nonadsorbed fraction from either DEAE- or CM-cellulose columns, suggesting that its isoelectric point was in the neutral pH region. The final preparation contained virtually no electron transfer components, ATPase, or NADH dehydrogenase. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed that the final preparation consisted of two major protein components with molecular weights of 36,000 and 9,400. Active transport of alanine after incorporation of the alanine carrier into reconstituted proteoliposomes was driven not only by an artificial membrane potential generated by potassium ion diffusion via valinomycin but also by mitochondrial cytochrome oxidase incorporated into the same liposomes and supplemented with both cytochrome c and ascorbic acid. The membrane-integrated portion (TFo) of the ATPase complex uncoupled alanine transport by conducting protons across the membrane.", "contents": "Isolation of the alanine carrier from the membranes of a thermophilic bacterium and its reconstitution into vesicles capable of transport. A carrier protein mediating alanine transport was purified from the membranes of the thermophilic bacterium PS3, by ion exchange chromatography in the presence of both Triton X-100 and urea. The alanine carrier was recovered in the nonadsorbed fraction from either DEAE- or CM-cellulose columns, suggesting that its isoelectric point was in the neutral pH region. The final preparation contained virtually no electron transfer components, ATPase, or NADH dehydrogenase. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed that the final preparation consisted of two major protein components with molecular weights of 36,000 and 9,400. Active transport of alanine after incorporation of the alanine carrier into reconstituted proteoliposomes was driven not only by an artificial membrane potential generated by potassium ion diffusion via valinomycin but also by mitochondrial cytochrome oxidase incorporated into the same liposomes and supplemented with both cytochrome c and ascorbic acid. The membrane-integrated portion (TFo) of the ATPase complex uncoupled alanine transport by conducting protons across the membrane."}
{"id": "PMID:197319", "title": "Mutations affecting the binding, internalization, and lysosomal hydrolysis of low density lipoprotein in cultured human fibroblasts, lymphocytes, and aortic smooth muscle cells.", "content": "Studies comparing the metabolism of low density lipoprotein (LDL) in normal cells and in cells cultured from patients with homozygous familial hypercholesterolemia have disclosed the existence of a receptor for plasma LDL. This receptor has been identified on the surface of human fibroblasts, lymphocytes, and aortic smooth muscle cells. An extension of these studies to cell strains derived from patients with other single gene defects in cholesterol metabolism has provided additional insight into the normal mechanisms by which cells regulate their cholesterol content and how alterations in these genetic control mechanisms may predispose to atherosclerosis in man.", "contents": "Mutations affecting the binding, internalization, and lysosomal hydrolysis of low density lipoprotein in cultured human fibroblasts, lymphocytes, and aortic smooth muscle cells. Studies comparing the metabolism of low density lipoprotein (LDL) in normal cells and in cells cultured from patients with homozygous familial hypercholesterolemia have disclosed the existence of a receptor for plasma LDL. This receptor has been identified on the surface of human fibroblasts, lymphocytes, and aortic smooth muscle cells. An extension of these studies to cell strains derived from patients with other single gene defects in cholesterol metabolism has provided additional insight into the normal mechanisms by which cells regulate their cholesterol content and how alterations in these genetic control mechanisms may predispose to atherosclerosis in man."}
{"id": "PMID:197323", "title": "Chlorpromazine inhibits cholera toxin-induced intestinal hypersecretion.", "content": "The effect of chlorpromazine on cholera-toxin-induced intestinal fluid secretion (experimental cholera) has been tested in vivo in the mouse. It is shown that intramuscular injection of chlorpromazine 1 hr prior to toxin challenge effectively inhibits the net secretory response of the intestine. It is suggested that this effect might be due to inhibition of adenylate cyclase since chlorpromazine inhibits the increase of cyclic AMP concentration in vitro in mouse thymocytes incubated with cholera toxin.", "contents": "Chlorpromazine inhibits cholera toxin-induced intestinal hypersecretion. The effect of chlorpromazine on cholera-toxin-induced intestinal fluid secretion (experimental cholera) has been tested in vivo in the mouse. It is shown that intramuscular injection of chlorpromazine 1 hr prior to toxin challenge effectively inhibits the net secretory response of the intestine. It is suggested that this effect might be due to inhibition of adenylate cyclase since chlorpromazine inhibits the increase of cyclic AMP concentration in vitro in mouse thymocytes incubated with cholera toxin."}
{"id": "PMID:197324", "title": "Influence of dibutyryl cyclic AMP on the level of catecholamines and 5-hydroxytryptamine in discrete areas of rat brain.", "content": "Dibutyrul cyclic AMP (dbcAMP) was injected intracerebroventricularly into rats in doses of 50, 100 or 200 microgram. Noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) or 5-hydroxy indoleacetic acid (5-HIAA) concentrations were measured spectrophotofluorimetrically in discrete brain areas: cortex, hypothalamus, striatum, hippocampus with nucleus amygdala and nucleus accumbens (limbic system) and pons with medulla oblongata. DbcAMP (in each dosage administered) decreased, NA content of cortex and of pons with medulla oblongata. NA content in the hypothalamus and striatum was decreased only after the largest dose of dbcAMP. In the limbic system NA concentration was diminished after a dose of 100 or 200 microgram of dbcAMP. There was a decrease in DA level measured in the striatum alone after a dose of 100 microgram of dbcAMP. 5-HT concentration was increased in the striatum and the pons with medulla oblongata after each dose level of dbcAMP; in the cortex after a dose of 50 and 100 microgram; and in the hypothalamus after a dose of 200 microgram. 5-HIAA level was increased in the striatum, limbic system, pons with medulla oblongata after all doses of dbcAMP. We conclude that dbcAMP affects presynaptic central catecholaminergic and serotoninergic neurons in an opposite, manner, although discrete brain areas have a different susceptibility to dbcAMP action. These findings provide some explanation for the behavioural effects of dbcAMP.", "contents": "Influence of dibutyryl cyclic AMP on the level of catecholamines and 5-hydroxytryptamine in discrete areas of rat brain. Dibutyrul cyclic AMP (dbcAMP) was injected intracerebroventricularly into rats in doses of 50, 100 or 200 microgram. Noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) or 5-hydroxy indoleacetic acid (5-HIAA) concentrations were measured spectrophotofluorimetrically in discrete brain areas: cortex, hypothalamus, striatum, hippocampus with nucleus amygdala and nucleus accumbens (limbic system) and pons with medulla oblongata. DbcAMP (in each dosage administered) decreased, NA content of cortex and of pons with medulla oblongata. NA content in the hypothalamus and striatum was decreased only after the largest dose of dbcAMP. In the limbic system NA concentration was diminished after a dose of 100 or 200 microgram of dbcAMP. There was a decrease in DA level measured in the striatum alone after a dose of 100 microgram of dbcAMP. 5-HT concentration was increased in the striatum and the pons with medulla oblongata after each dose level of dbcAMP; in the cortex after a dose of 50 and 100 microgram; and in the hypothalamus after a dose of 200 microgram. 5-HIAA level was increased in the striatum, limbic system, pons with medulla oblongata after all doses of dbcAMP. We conclude that dbcAMP affects presynaptic central catecholaminergic and serotoninergic neurons in an opposite, manner, although discrete brain areas have a different susceptibility to dbcAMP action. These findings provide some explanation for the behavioural effects of dbcAMP."}
{"id": "PMID:197357", "title": "[Islet cell tumors. Diagnostic and operative aspects (author's transl)].", "content": "Islet cell tumors have been described the past 25 years in frequent series. Multiple symptoms lead often to prolongation of disease and misinterpretation of diagnosis. Because of its rarity most authors report only few cases. We had the chance to observe 24 patients of which four had carcinoma within 12 years. Symptoms, clinic, different surgical procedures are described. Clinical difference seems to exists between benigne and malignant islet cell tumors.", "contents": "[Islet cell tumors. Diagnostic and operative aspects (author's transl)]. Islet cell tumors have been described the past 25 years in frequent series. Multiple symptoms lead often to prolongation of disease and misinterpretation of diagnosis. Because of its rarity most authors report only few cases. We had the chance to observe 24 patients of which four had carcinoma within 12 years. Symptoms, clinic, different surgical procedures are described. Clinical difference seems to exists between benigne and malignant islet cell tumors."}
{"id": "PMID:197358", "title": "Malignant fibrous histiocytoma of the head and neck.", "content": "Review of the literature reveals of 29 cases of fibrous histiocytoma of the deep structures of the head and neck. Three additional cases are reported: a multicentric case involving the submandibular gland with metastases to the lungs; and intraosseous tumor of the mandible locally invasive; and a submental tumor which rapidly recurred after simple excision. A metastatic potential of 22% is established. The historm, nomenclature, histopathology and clinical features are reviewed. The value of electron microscopy and tissue culture in arriving at the current diagnosis are stressed. Wide excision is the treatment of choice.", "contents": "Malignant fibrous histiocytoma of the head and neck. Review of the literature reveals of 29 cases of fibrous histiocytoma of the deep structures of the head and neck. Three additional cases are reported: a multicentric case involving the submandibular gland with metastases to the lungs; and intraosseous tumor of the mandible locally invasive; and a submental tumor which rapidly recurred after simple excision. A metastatic potential of 22% is established. The historm, nomenclature, histopathology and clinical features are reviewed. The value of electron microscopy and tissue culture in arriving at the current diagnosis are stressed. Wide excision is the treatment of choice."}
{"id": "PMID:197359", "title": "Chronic otitis media and hearing loss in the Eskimo population of Canada.", "content": "Chronic otitis media and hearing loss is a major health problem today in the Canadian Eskimo. The subject is reviewed and the findings of projects and a survey that have been carried out recently are discussed. A modality of treatment is proposed which is based upon the findings of the projects, the survey and other information that is available at the present time.", "contents": "Chronic otitis media and hearing loss in the Eskimo population of Canada. Chronic otitis media and hearing loss is a major health problem today in the Canadian Eskimo. The subject is reviewed and the findings of projects and a survey that have been carried out recently are discussed. A modality of treatment is proposed which is based upon the findings of the projects, the survey and other information that is available at the present time."}
{"id": "PMID:197364", "title": "Levels of cyclic 3'-5' -adenosine monophosphate (cAMP) in maintenance cultures of rat hepatocytes in response to insulin and glucagon.", "content": "Under conditions of short-term stimulation of lipogenesis by insulin in maintenance cultures of hepatocytes from starved rats, basal levels of cyclic 3'-5' -adenosine monophosphate (cAMP) are invariant. Glucagon signals increased levels of cAMP and severely diminishes lipogenesis. Insulin partially counteracts both glucagon effects.", "contents": "Levels of cyclic 3'-5' -adenosine monophosphate (cAMP) in maintenance cultures of rat hepatocytes in response to insulin and glucagon. Under conditions of short-term stimulation of lipogenesis by insulin in maintenance cultures of hepatocytes from starved rats, basal levels of cyclic 3'-5' -adenosine monophosphate (cAMP) are invariant. Glucagon signals increased levels of cAMP and severely diminishes lipogenesis. Insulin partially counteracts both glucagon effects."}
{"id": "PMID:197373", "title": "[Effect of chronic action of cadmium sulfate on various biochemical indices of blood serum and on the histological picture of rat liver and kidneys].", "content": "Male rats weighing 180-220 g were given CdSO4, 0,4 mg/kg body weight subcutaneously once a week for 6-12 months. The animals were killed after 6, 9, 12 months and following blood serum levels were determined: total protein, albumin, globulin, GPT, GOT, Al.P. and urea. The tissue tissue samples from liver and kidneys were examined histologically (acid and alkaline phosphatase). After 9 months, the difference between values of biochemical indices in the exposed and control groups was statistically significant. It has been found that the observed biochemical indices show correlation with the extent of morphological changes in liver and kidneys. These degenerative changes became more intense in the liver than in the kidneys.", "contents": "[Effect of chronic action of cadmium sulfate on various biochemical indices of blood serum and on the histological picture of rat liver and kidneys]. Male rats weighing 180-220 g were given CdSO4, 0,4 mg/kg body weight subcutaneously once a week for 6-12 months. The animals were killed after 6, 9, 12 months and following blood serum levels were determined: total protein, albumin, globulin, GPT, GOT, Al.P. and urea. The tissue tissue samples from liver and kidneys were examined histologically (acid and alkaline phosphatase). After 9 months, the difference between values of biochemical indices in the exposed and control groups was statistically significant. It has been found that the observed biochemical indices show correlation with the extent of morphological changes in liver and kidneys. These degenerative changes became more intense in the liver than in the kidneys."}
{"id": "PMID:197374", "title": "[Level of blood serum lipids in rats treated with detergents].", "content": "Male Wistar rats were treated intraperitoneally once per week for 12 weeks with following detergents: Olbrotol-18 (nonionic detergent), a product of etheric condensation of 18 moles of ethylene oxide to 1 mole of the mixture of olein alcohol and cetyl alkohol in ratio 1:1, in a dose of 10 mg/kg; SBO (anionic detergent), sodium 2-ethylhexylsulfosuccinate, in a dose of 10 mg/kg and Sterinol (cationic detergent), benzalkonium bromide, in a dose of 0.6 mg/kg. The control rats were injected with 0.9% saline solution. The content of total cholesterol, beta-lipoproteins and total lipids in serum were estimated. The increase of total cholesterol and the decrease of beta-lipoproteins content in serum of rats after all used detergents were observed as compared with the control. The increase of total lipid content only after long-term treatment with Olbrotol-18 was found. It is concluded that long term intraperitoneal treatment with detergents changes similarly the contents of total cholesterol and of beta-lipoproteins in blood serum of rats.", "contents": "[Level of blood serum lipids in rats treated with detergents]. Male Wistar rats were treated intraperitoneally once per week for 12 weeks with following detergents: Olbrotol-18 (nonionic detergent), a product of etheric condensation of 18 moles of ethylene oxide to 1 mole of the mixture of olein alcohol and cetyl alkohol in ratio 1:1, in a dose of 10 mg/kg; SBO (anionic detergent), sodium 2-ethylhexylsulfosuccinate, in a dose of 10 mg/kg and Sterinol (cationic detergent), benzalkonium bromide, in a dose of 0.6 mg/kg. The control rats were injected with 0.9% saline solution. The content of total cholesterol, beta-lipoproteins and total lipids in serum were estimated. The increase of total cholesterol and the decrease of beta-lipoproteins content in serum of rats after all used detergents were observed as compared with the control. The increase of total lipid content only after long-term treatment with Olbrotol-18 was found. It is concluded that long term intraperitoneal treatment with detergents changes similarly the contents of total cholesterol and of beta-lipoproteins in blood serum of rats."}
{"id": "PMID:197375", "title": "[Behavior of various biochemical indices of liver efficiency and of selected blood serum electrolytes in workers exposed to beryllium].", "content": "In 30 workers being occupationally exposed to beryllium, examinations of biochemical indicators of liver efficiency were carried out: activity of alanine and asparagine aminotraspherase and basic phosphatases, cholinesterase, content of total protein and its fraction. Levels of electrolytes were determined: calcium, potassium, phosphorus, and magnesium. The above examinations were also carried out on 30 persons who have no contact with beryllium. The obtained results were subjected to statistical analysis. In 10 persons from the group exposed to beryllium one found lowering of the level of magnesium in blood serum, whereas in the control group the level of this electrolyte was correct in all persons. As to the results on the level of magnesium, in both groups high statistical significance was found (p less than 0,01). A dependence was found between the amount of workers and the lowered level of magnesium in blood serum and the duration of occupational exposure to beryllium. The comparison of the remaining results of examinations of both groups did not reveal any statistically significant differences or the differences were at the point of statistical significance.", "contents": "[Behavior of various biochemical indices of liver efficiency and of selected blood serum electrolytes in workers exposed to beryllium]. In 30 workers being occupationally exposed to beryllium, examinations of biochemical indicators of liver efficiency were carried out: activity of alanine and asparagine aminotraspherase and basic phosphatases, cholinesterase, content of total protein and its fraction. Levels of electrolytes were determined: calcium, potassium, phosphorus, and magnesium. The above examinations were also carried out on 30 persons who have no contact with beryllium. The obtained results were subjected to statistical analysis. In 10 persons from the group exposed to beryllium one found lowering of the level of magnesium in blood serum, whereas in the control group the level of this electrolyte was correct in all persons. As to the results on the level of magnesium, in both groups high statistical significance was found (p less than 0,01). A dependence was found between the amount of workers and the lowered level of magnesium in blood serum and the duration of occupational exposure to beryllium. The comparison of the remaining results of examinations of both groups did not reveal any statistically significant differences or the differences were at the point of statistical significance."}
{"id": "PMID:197376", "title": "[Specific surface factor of dust particles and preliminary selection of silica dusts].", "content": "The results of particles analysis of three kinds of silica dust by means of miscroscopy and sedimentation in Andreasen's pipette served as a base for the determination of factor phi specific for particle surface. This factor is expressed as a ratio of the mean projected diameter (dp) to the aerodynamic diameter (d). The formula of the factor is: (formula: see text). The value of factor phi for tested silica dusts ranges from 2.0 to 2.6 (mean value--2.3), while the variability coefficient is 13.5%. Taking into account the value of factor phi determined by experiment and the value of dispersion of silica dust particles, the expected permeability of the selector (elutriator) and the deposition of dust in lungs were calculated.", "contents": "[Specific surface factor of dust particles and preliminary selection of silica dusts]. The results of particles analysis of three kinds of silica dust by means of miscroscopy and sedimentation in Andreasen's pipette served as a base for the determination of factor phi specific for particle surface. This factor is expressed as a ratio of the mean projected diameter (dp) to the aerodynamic diameter (d). The formula of the factor is: (formula: see text). The value of factor phi for tested silica dusts ranges from 2.0 to 2.6 (mean value--2.3), while the variability coefficient is 13.5%. Taking into account the value of factor phi determined by experiment and the value of dispersion of silica dust particles, the expected permeability of the selector (elutriator) and the deposition of dust in lungs were calculated."}
{"id": "PMID:197379", "title": "Evidence that a separate particle containing B-apoprotein is present in high-density lipoproteins from perfused rat liver.", "content": "High-density lipoproteins (HDL) (1.075 less than d less than 1.175) from perfusates of rat liver, unlike those of blood plasma, contain protein with the properties of B-apolipoprotein. This protein remains near the origin upon electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate, has beta electrophoretic mobility in agarose gel, is insoluble in tetramethylurea, and precipitates with antisera to the B-apoprotein isolated from low-density lipoprotein. B-apolipoprotein in HDL from perfusates binds to concanavalin-A Sepharose and can thus be separated from the characteristic HDL, the chemical and physical properties of which are otherwise preserved. These observations suggest that in addition to the discoidal lipoproteins, another particle that contains B-apoprotein exists in HDL of perfusates.", "contents": "Evidence that a separate particle containing B-apoprotein is present in high-density lipoproteins from perfused rat liver. High-density lipoproteins (HDL) (1.075 less than d less than 1.175) from perfusates of rat liver, unlike those of blood plasma, contain protein with the properties of B-apolipoprotein. This protein remains near the origin upon electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate, has beta electrophoretic mobility in agarose gel, is insoluble in tetramethylurea, and precipitates with antisera to the B-apoprotein isolated from low-density lipoprotein. B-apolipoprotein in HDL from perfusates binds to concanavalin-A Sepharose and can thus be separated from the characteristic HDL, the chemical and physical properties of which are otherwise preserved. These observations suggest that in addition to the discoidal lipoproteins, another particle that contains B-apoprotein exists in HDL of perfusates."}
{"id": "PMID:197380", "title": "[Mechanism of action of glucose on L-asparaginase synthesis by Escherichia coli bacteria].", "content": "The synthesis of L-asparaginase in Escherichia coli W and E. coli K-12 was almost completely supressed if glucose was added at a concentration of 0.5 per cent to a growth medium. The level of L-asparaginase synthesis decreased by ca. 75 per cent as a result of cyamutations when the bacteria could not produce cyclo-3',5'-AMP (cAMP). Apparently, a decrease in the intracellular content of cAMP caused by glucose could not be the only factor inhibiting L-asparaginase synthesis. Lactate was found to stimulate L-asparaginase synthesis. Glucose caused the catabolite repression and catabolite inhibition of the components of a system involved in lactate transport. The inhibition of L-asparaginase synthesis by glucose seems to be due, at least partly, to the fact that it prevents the assimilation of lactate by the cells, as well as the utilization of some other compounds which stimulate synthesis of this enzyme.", "contents": "[Mechanism of action of glucose on L-asparaginase synthesis by Escherichia coli bacteria]. The synthesis of L-asparaginase in Escherichia coli W and E. coli K-12 was almost completely supressed if glucose was added at a concentration of 0.5 per cent to a growth medium. The level of L-asparaginase synthesis decreased by ca. 75 per cent as a result of cyamutations when the bacteria could not produce cyclo-3',5'-AMP (cAMP). Apparently, a decrease in the intracellular content of cAMP caused by glucose could not be the only factor inhibiting L-asparaginase synthesis. Lactate was found to stimulate L-asparaginase synthesis. Glucose caused the catabolite repression and catabolite inhibition of the components of a system involved in lactate transport. The inhibition of L-asparaginase synthesis by glucose seems to be due, at least partly, to the fact that it prevents the assimilation of lactate by the cells, as well as the utilization of some other compounds which stimulate synthesis of this enzyme."}
{"id": "PMID:197385", "title": "The effect of exogenous oestrogens on depression in menopausal women.", "content": "A study of the effects of conjugated oestrogens (Premarin) upon the depression scores of depressed and non-depressed menopausal women was carried out. Depression levels were obtained for both groups before and after four weeks of hormone replacement therapy. The Beck Depression Inventory (BDI) was used to assess depression levels, while a semistructured interview provided information related to the physiological, psychological and sociocultural stresses affecting individual women. Depression scores of the depressed group did not improve within the given treatment period, in contrast with improved scores for the non-depressed subjects who reported increased feelings of well-being following hormone replacement therapy.", "contents": "The effect of exogenous oestrogens on depression in menopausal women. A study of the effects of conjugated oestrogens (Premarin) upon the depression scores of depressed and non-depressed menopausal women was carried out. Depression levels were obtained for both groups before and after four weeks of hormone replacement therapy. The Beck Depression Inventory (BDI) was used to assess depression levels, while a semistructured interview provided information related to the physiological, psychological and sociocultural stresses affecting individual women. Depression scores of the depressed group did not improve within the given treatment period, in contrast with improved scores for the non-depressed subjects who reported increased feelings of well-being following hormone replacement therapy."}
{"id": "PMID:197386", "title": "Solid phase indirect radioimmunoassay: standardization and applications in viral serology.", "content": "In solid phase indirect radioimmunoassay (IRIA) antiviral immunoglobulins (Ig) bind specifically to the viral antigen fixed onto wells of microtiter plates. Radioactively labeled (125I) anti-Ig can be used to detect these antiviral antibodies. The sensitivity of the IRIA depends on the amount of antigen in the microtiter wells and the concentration of the 125I-labeled anti-Ig used. To standardize the assay, a method of antigen titration in the IRIA was devised, using parainfluenza type 1 viruses as antigens. The IRIA provides a means to titrate viral antigens with different biologic activities and antibodies against them. A binding inhibition test (BIT) based on IRIA allows the antigenic analysis of different virus strains, as is demonstrated for two closely related parainfluenza type 1 virus strains.", "contents": "Solid phase indirect radioimmunoassay: standardization and applications in viral serology. In solid phase indirect radioimmunoassay (IRIA) antiviral immunoglobulins (Ig) bind specifically to the viral antigen fixed onto wells of microtiter plates. Radioactively labeled (125I) anti-Ig can be used to detect these antiviral antibodies. The sensitivity of the IRIA depends on the amount of antigen in the microtiter wells and the concentration of the 125I-labeled anti-Ig used. To standardize the assay, a method of antigen titration in the IRIA was devised, using parainfluenza type 1 viruses as antigens. The IRIA provides a means to titrate viral antigens with different biologic activities and antibodies against them. A binding inhibition test (BIT) based on IRIA allows the antigenic analysis of different virus strains, as is demonstrated for two closely related parainfluenza type 1 virus strains."}
{"id": "PMID:197383", "title": "The site of synthesis and functions of acute phase plasma proteins: close relationship with the reticulo-endothelial system.", "content": "The evidence that the acute phase glycoproteins of plasma are synthesized by the liver parenchymal cells is critically examined, and is found to be inconclusive. Some evidence is cited which favors the reticulo-endothelial system (RES) in general, and Kupffer cells in particular, as the site of synthesis of these proteins: 1. The entire RES contains non-glycogenic periodic acid Schiff-positive substances. 2. The diseases which affect glycoprotein levels are also known to affect the function of the RES. 3. When the animal is subjected to stress, the RES function is initially depressed and then stimulated. A similar biphasic behavior is shown by plasma glycoprotein levels. 4. Adrenal cortico-steriods are the major regulators of the RES function and of the synthesis of acute phase proteins. Moreover, both are stimulated at low concentrations, and depressed at high concentrations of the hormone. Some of the glycoproteins of the acute phase (prothrombin, the third component of complement, haptoglobin, transferrin and ceruloplasmin) have defense-related functions. The others seem to participate in phenomena like detoxification, promotion of phagocytosis, wound healing, prevention of tissue injury by lysosomal enzymes, prevention of trauma and recovery from inflammation. It is proposed that the acute phase proteins, together with antibodies, form major components of the definse system, and the RES attempts to deal with injury by mobilization of increased amounts of these substances.", "contents": "The site of synthesis and functions of acute phase plasma proteins: close relationship with the reticulo-endothelial system. The evidence that the acute phase glycoproteins of plasma are synthesized by the liver parenchymal cells is critically examined, and is found to be inconclusive. Some evidence is cited which favors the reticulo-endothelial system (RES) in general, and Kupffer cells in particular, as the site of synthesis of these proteins: 1. The entire RES contains non-glycogenic periodic acid Schiff-positive substances. 2. The diseases which affect glycoprotein levels are also known to affect the function of the RES. 3. When the animal is subjected to stress, the RES function is initially depressed and then stimulated. A similar biphasic behavior is shown by plasma glycoprotein levels. 4. Adrenal cortico-steriods are the major regulators of the RES function and of the synthesis of acute phase proteins. Moreover, both are stimulated at low concentrations, and depressed at high concentrations of the hormone. Some of the glycoproteins of the acute phase (prothrombin, the third component of complement, haptoglobin, transferrin and ceruloplasmin) have defense-related functions. The others seem to participate in phenomena like detoxification, promotion of phagocytosis, wound healing, prevention of tissue injury by lysosomal enzymes, prevention of trauma and recovery from inflammation. It is proposed that the acute phase proteins, together with antibodies, form major components of the definse system, and the RES attempts to deal with injury by mobilization of increased amounts of these substances."}
{"id": "PMID:197384", "title": "Roles of prostaglandins suggested by the prostaglandin agonist/antagonist actions of local anaesthetic, anti-arrhythmic, anti-malarial, tricyclic anti-depressant and methyl xanthine compounds. Effects on membranes and on nucleic acid function.", "content": "We have recently found that local anaesthetic, anti-malarial, anti-arrhythmic, tricyclic antidepressant and methyl xanthine compounds behave as prostaglandin antagonists at drug concentrations readily attainable in human body fluids. We have also found that various hormones, including prolactin, vasopressin and angiotensin when present in physiological concentrations can be potent stimulators of prostaglandin synthesis. Cortisol has no effect on basal prostaglandin systhesis but in physiological concentrations is able to reverse the effects of other hormones. The drugs are thought to act mainly by interfering with either calcium interactions with membranes, or with cyclic nucleotide synthesis or degradation or with nucleic acid function. We propose that prostaglandins play crucial roles at all three points. The hypothesis leads to new approaches to many aspects of cell regulation, to the functions of many systems, especially the neuromuscular, cardiovascular, renal and respiratory systems. It also has profound implications for drug design and evaluation and for the understanding of many clinical disorders.", "contents": "Roles of prostaglandins suggested by the prostaglandin agonist/antagonist actions of local anaesthetic, anti-arrhythmic, anti-malarial, tricyclic anti-depressant and methyl xanthine compounds. Effects on membranes and on nucleic acid function. We have recently found that local anaesthetic, anti-malarial, anti-arrhythmic, tricyclic antidepressant and methyl xanthine compounds behave as prostaglandin antagonists at drug concentrations readily attainable in human body fluids. We have also found that various hormones, including prolactin, vasopressin and angiotensin when present in physiological concentrations can be potent stimulators of prostaglandin synthesis. Cortisol has no effect on basal prostaglandin systhesis but in physiological concentrations is able to reverse the effects of other hormones. The drugs are thought to act mainly by interfering with either calcium interactions with membranes, or with cyclic nucleotide synthesis or degradation or with nucleic acid function. We propose that prostaglandins play crucial roles at all three points. The hypothesis leads to new approaches to many aspects of cell regulation, to the functions of many systems, especially the neuromuscular, cardiovascular, renal and respiratory systems. It also has profound implications for drug design and evaluation and for the understanding of many clinical disorders."}
{"id": "PMID:197387", "title": "Xanthine dehydrogenase from Drosophila melanogaster: a comparison of the kinetic parameters of the pure enzyme from two wild-type isoalleles differing at a putative regulatory site.", "content": "Xanthine dehydrogenase (XDH) from Drosophila melanogaster has been purified to homogeneity by immunoaffinity chromatography, and its kinetic parameters determined. Drosophila XDH exhibits ordered binding for substrate and NAD+, analogous to the corresponding enzymes from vertebrate sources. The wild-type enzyme exhibits a Km for xanthine of 2.4 X 10(-5) M, and for NAD+ of 4.0 X 10(-5) M. XDH purified from a genetic variant exhibiting elevated levels of enzyme activity has similar kinetic constants. The results provide further evidence that the site of variation in the latter strain results in higher steady state numbers of XDH molecules per fly.", "contents": "Xanthine dehydrogenase from Drosophila melanogaster: a comparison of the kinetic parameters of the pure enzyme from two wild-type isoalleles differing at a putative regulatory site. Xanthine dehydrogenase (XDH) from Drosophila melanogaster has been purified to homogeneity by immunoaffinity chromatography, and its kinetic parameters determined. Drosophila XDH exhibits ordered binding for substrate and NAD+, analogous to the corresponding enzymes from vertebrate sources. The wild-type enzyme exhibits a Km for xanthine of 2.4 X 10(-5) M, and for NAD+ of 4.0 X 10(-5) M. XDH purified from a genetic variant exhibiting elevated levels of enzyme activity has similar kinetic constants. The results provide further evidence that the site of variation in the latter strain results in higher steady state numbers of XDH molecules per fly."}
{"id": "PMID:197388", "title": "Methionine biosynthesis in Saccharomyces cerevisiae. II. Gene-enzyme relationships in the sulfate assimilation pathway.", "content": "In Saccharomyces cerevisiae, the products of eleven different genes are needed for a functional sulfate assimilation pathway. Only five enzymatic steps are known in this pathway. The study of the gene-enzyme relationships has shown that the enzymes catalysing two of these steps are probably heteropolymeric. Moreover, mutations in three unlinked genes lead to multiple enzymatic losses. Different hypotheses are made to account for these results.", "contents": "Methionine biosynthesis in Saccharomyces cerevisiae. II. Gene-enzyme relationships in the sulfate assimilation pathway. In Saccharomyces cerevisiae, the products of eleven different genes are needed for a functional sulfate assimilation pathway. Only five enzymatic steps are known in this pathway. The study of the gene-enzyme relationships has shown that the enzymes catalysing two of these steps are probably heteropolymeric. Moreover, mutations in three unlinked genes lead to multiple enzymatic losses. Different hypotheses are made to account for these results."}
{"id": "PMID:197389", "title": "Characterization of a regulatory mutant of fructose 1,6-bisphosphatase in Saccharomyces carlsbergensis.", "content": "The fdp mutation has been localized on the genome of Saccharomyces carlsbergensis, on chromosome II, between lys2 and tyr1, at a man distance of 31 centimorgan from lys2. Since the fdp mutant does not grow on glucose, fructose, mannose and sucrose, hexose transport and a number of enzymes of carbon metabolism were tested, but no significant differences could be found between the wild type and the mutant. Only the regulatory properties of glycogen synthetase are changed in the mutant, but it is doubtful whether this can explain its phenotype. The disorganization of carbon metabolism of the mutant upon addition of glucose to the medium was analyzed in more detail. The most prominent feature observed until now is the accumulation of free glucose and hexose phosphates in the cell. This result indicates that somehow the feedback control between hexose transport and metabolism is impaired. Hexose phosphates are known to be toxic to many cells, including yeast. Therefore, accumulation of hexose phosphates in the presence of glucose in the medium, can explain the absence of growth on this carbon source.", "contents": "Characterization of a regulatory mutant of fructose 1,6-bisphosphatase in Saccharomyces carlsbergensis. The fdp mutation has been localized on the genome of Saccharomyces carlsbergensis, on chromosome II, between lys2 and tyr1, at a man distance of 31 centimorgan from lys2. Since the fdp mutant does not grow on glucose, fructose, mannose and sucrose, hexose transport and a number of enzymes of carbon metabolism were tested, but no significant differences could be found between the wild type and the mutant. Only the regulatory properties of glycogen synthetase are changed in the mutant, but it is doubtful whether this can explain its phenotype. The disorganization of carbon metabolism of the mutant upon addition of glucose to the medium was analyzed in more detail. The most prominent feature observed until now is the accumulation of free glucose and hexose phosphates in the cell. This result indicates that somehow the feedback control between hexose transport and metabolism is impaired. Hexose phosphates are known to be toxic to many cells, including yeast. Therefore, accumulation of hexose phosphates in the presence of glucose in the medium, can explain the absence of growth on this carbon source."}
{"id": "PMID:197390", "title": "Mutants of Saccharomyces cerevisiae resistant to carbon catabolite repression.", "content": "Mutants with defective carbon catabolite repression have been isolated in the yeast Saccharomyces cerevisiae using a selective procedure. This was based on the fact that invertase is a glucose repressible cell wall enzyme which slowly hydrolyses raffinose to yield fructose and that the inhibitory effects of 2-deoxyglucose can be counteracted by fructose. Repressed cells were plated on a raffinose--2-doexyglucose medium and the resistant cells growing up into colonies were tested for glucose non-repressible invertase and maltase. The yield of regulatory mutants was very high. All were equally derepressed for invertase and maltase, no mutants were obtained with only non-repressible invertase synthesis which was the selected function. A total of 61 mutants isolated in different strains were allele tested and could be attributed to three genes. They were all recessive. Mutants in one gene had reduced hexokinase activities, the other class, located in a centromere linked gene, had elevated hexokinase levels and was inhibited by maltose. Mutants in a third gene were isolated on a 2-deoxyglucose galactose medium and had normal hexokinase levels. A partial derepression was observed for malate dehydrogenase in all mutants. Isocitrate lyase, however, was still fully repressible.", "contents": "Mutants of Saccharomyces cerevisiae resistant to carbon catabolite repression. Mutants with defective carbon catabolite repression have been isolated in the yeast Saccharomyces cerevisiae using a selective procedure. This was based on the fact that invertase is a glucose repressible cell wall enzyme which slowly hydrolyses raffinose to yield fructose and that the inhibitory effects of 2-deoxyglucose can be counteracted by fructose. Repressed cells were plated on a raffinose--2-doexyglucose medium and the resistant cells growing up into colonies were tested for glucose non-repressible invertase and maltase. The yield of regulatory mutants was very high. All were equally derepressed for invertase and maltase, no mutants were obtained with only non-repressible invertase synthesis which was the selected function. A total of 61 mutants isolated in different strains were allele tested and could be attributed to three genes. They were all recessive. Mutants in one gene had reduced hexokinase activities, the other class, located in a centromere linked gene, had elevated hexokinase levels and was inhibited by maltose. Mutants in a third gene were isolated on a 2-deoxyglucose galactose medium and had normal hexokinase levels. A partial derepression was observed for malate dehydrogenase in all mutants. Isocitrate lyase, however, was still fully repressible."}
{"id": "PMID:197391", "title": "Isolation and characterization of yeast mutants defective in intermediary carbon metabolism and in carbon catabolite derepression.", "content": "Yeast mutants deficient in the constitutive ADHI (adc 1) were used for the isolation of mutants with deficiencies of the intermediary carbon metabolism, and of mutants defective in carbon catabolite derepression. Mutants were recognized by their inability to grow on YEP-glycerol and/or on ethanol synthetic complete medium. They were either defective in isocitrate lyase (ic11), succinate dehydrogenase (sdh1), or malate dehydrogenase (mdh1, mdh2), mdh-mutants could not uniformely be appointed to one of the known MDH isozymes. Homozygous mdh and sdh1 diploids are unable to sporulate. Three gene loci could be identified by mutants pleiotropically defective in many or all of the enzymes tested In ccr 1 mutants, derepression of isocitrate lyase, fructose-1,6-diphosphatase, ADHII and possibly of the cytoplasmic MDH is prevented, whereas the mitochondrial TCA-cycle enzymes, succinate dehydrogenase and malate dehydrogenase, are not significantly affected. CCR2 and CCR3 have quite similar action spectra. Both genes are obviously necessary for derepression of all enzymes tested. It could be shown that ccr1, ccr2 and ccr3 mutants are not respiratory deficient.", "contents": "Isolation and characterization of yeast mutants defective in intermediary carbon metabolism and in carbon catabolite derepression. Yeast mutants deficient in the constitutive ADHI (adc 1) were used for the isolation of mutants with deficiencies of the intermediary carbon metabolism, and of mutants defective in carbon catabolite derepression. Mutants were recognized by their inability to grow on YEP-glycerol and/or on ethanol synthetic complete medium. They were either defective in isocitrate lyase (ic11), succinate dehydrogenase (sdh1), or malate dehydrogenase (mdh1, mdh2), mdh-mutants could not uniformely be appointed to one of the known MDH isozymes. Homozygous mdh and sdh1 diploids are unable to sporulate. Three gene loci could be identified by mutants pleiotropically defective in many or all of the enzymes tested In ccr 1 mutants, derepression of isocitrate lyase, fructose-1,6-diphosphatase, ADHII and possibly of the cytoplasmic MDH is prevented, whereas the mitochondrial TCA-cycle enzymes, succinate dehydrogenase and malate dehydrogenase, are not significantly affected. CCR2 and CCR3 have quite similar action spectra. Both genes are obviously necessary for derepression of all enzymes tested. It could be shown that ccr1, ccr2 and ccr3 mutants are not respiratory deficient."}
{"id": "PMID:197392", "title": "Endonuclease for apurinic sites in yeast. Comparison of the enzyme activity in the wild type and in rad mutants of Saccharomyces cerevisiae to MNS.", "content": "It was found that yeast cells contain an endonuclease specific for apurinic sites in DNA which has no effect on DNA with normal strands or on strands with alkylated sites. The enzyme activity was studied in the RAD strain and in rad 6, rad 18-2 and rad 21 mutants, all very sensitive to MMS, as compared to the wild type. The level of endonuclease activity does not differ much between the tested strains, regardless of their differences in susceptibility to MMS. The enzyme activity is not induced by pretreatment of the cells with this mutagen.", "contents": "Endonuclease for apurinic sites in yeast. Comparison of the enzyme activity in the wild type and in rad mutants of Saccharomyces cerevisiae to MNS. It was found that yeast cells contain an endonuclease specific for apurinic sites in DNA which has no effect on DNA with normal strands or on strands with alkylated sites. The enzyme activity was studied in the RAD strain and in rad 6, rad 18-2 and rad 21 mutants, all very sensitive to MMS, as compared to the wild type. The level of endonuclease activity does not differ much between the tested strains, regardless of their differences in susceptibility to MMS. The enzyme activity is not induced by pretreatment of the cells with this mutagen."}
{"id": "PMID:197398", "title": "Protein inhibitors of phosphorylase phosphatase and cyclic AMP-dependent protein kinase from rabbit skeleta muscle.", "content": "A heat-and acid-stable protein inhibitor of phosphorylase phosphatase is present in a highly purified preparation of protein inhibitor of cyclic AMP-dependent protein kinase from rabbit skeletal muscle. Although these two inhibitors have strikingly similar properties to each other, such as sensitivity to trypsin and behavior on gel permeation chromatography, they can be separated by polyacrylamide disc gel electrophoresis. This indicates that the phosphatase-inhibitory and kinase-inhibitory activities reside with different protein species. The inhibition of both the enzymes is not altered by incubating the inhibitor preparation with a general phosphoprotein phosphatase, with phosvitin kinase, or with cyclic AMP-dependent protein kinase. Inhibition of phosphorylase phosphatase is of a non-competitive type supporting the idea that the phosphatase inhibitor is not an alternative substrate for the enzyme. Inhibition of phosphatase activity is selective in that it does no occur when phosphorylated histone or phosphorylated protamine are used as substrates.", "contents": "Protein inhibitors of phosphorylase phosphatase and cyclic AMP-dependent protein kinase from rabbit skeleta muscle. A heat-and acid-stable protein inhibitor of phosphorylase phosphatase is present in a highly purified preparation of protein inhibitor of cyclic AMP-dependent protein kinase from rabbit skeletal muscle. Although these two inhibitors have strikingly similar properties to each other, such as sensitivity to trypsin and behavior on gel permeation chromatography, they can be separated by polyacrylamide disc gel electrophoresis. This indicates that the phosphatase-inhibitory and kinase-inhibitory activities reside with different protein species. The inhibition of both the enzymes is not altered by incubating the inhibitor preparation with a general phosphoprotein phosphatase, with phosvitin kinase, or with cyclic AMP-dependent protein kinase. Inhibition of phosphorylase phosphatase is of a non-competitive type supporting the idea that the phosphatase inhibitor is not an alternative substrate for the enzyme. Inhibition of phosphatase activity is selective in that it does no occur when phosphorylated histone or phosphorylated protamine are used as substrates."}
{"id": "PMID:197399", "title": "Inhibition of rabbit skeletal muscle phosphorylase phosphatase by spermine.", "content": "The effect of three naturally occurring polyamines (putrescine, spermidine, and spermine) on the activity of rabbit skeletal muscle phosphorylase phosphatase was investigated. Only spermine significantly inhibited the enzyme. The mode of inhibition (ki value of 0.3 mM) of the phosphatase by spermine appears to be different from that caused by divalent metal ions or by other organic cations, such as arginine and lysine esters, since it is noncompetitive with respect to the substrate, phosphorylase a.", "contents": "Inhibition of rabbit skeletal muscle phosphorylase phosphatase by spermine. The effect of three naturally occurring polyamines (putrescine, spermidine, and spermine) on the activity of rabbit skeletal muscle phosphorylase phosphatase was investigated. Only spermine significantly inhibited the enzyme. The mode of inhibition (ki value of 0.3 mM) of the phosphatase by spermine appears to be different from that caused by divalent metal ions or by other organic cations, such as arginine and lysine esters, since it is noncompetitive with respect to the substrate, phosphorylase a."}
{"id": "PMID:197400", "title": "Studies on the adrenal cortex of hypophysectomized rats: a model for abnormal cellular atrophy and death.", "content": "Biochemical and ultrastructural studies indicate that the atrophy of adrenal cortex in hypoyhysectomized rats involves the following changes: (1) One to two days after hypophysectomy, there is loss of \"template activity\" resulting from cumulative DNA-damage and heterochromatinization. In vivo ACTH-administration led to recuperation of these cells, indicating damage during hypophysectomized state to be reversible. (2) If the duration of hypophysectomy is prolonged, some of the cells become irreversibly damaged and can no longer recuperate after in vivo ACTH administration. (3) The period of most rapid cell death is from the third to seventh day after hypophysectomy. The cause of cell death is probably due to membrane damage in the absence of protein synthesis, leading to lysis of the cells. Lysozomes and macrophages are apparently not involved.", "contents": "Studies on the adrenal cortex of hypophysectomized rats: a model for abnormal cellular atrophy and death. Biochemical and ultrastructural studies indicate that the atrophy of adrenal cortex in hypoyhysectomized rats involves the following changes: (1) One to two days after hypophysectomy, there is loss of \"template activity\" resulting from cumulative DNA-damage and heterochromatinization. In vivo ACTH-administration led to recuperation of these cells, indicating damage during hypophysectomized state to be reversible. (2) If the duration of hypophysectomy is prolonged, some of the cells become irreversibly damaged and can no longer recuperate after in vivo ACTH administration. (3) The period of most rapid cell death is from the third to seventh day after hypophysectomy. The cause of cell death is probably due to membrane damage in the absence of protein synthesis, leading to lysis of the cells. Lysozomes and macrophages are apparently not involved."}
{"id": "PMID:197404", "title": "[Electromyography as a diagnostic aid (author's transl)].", "content": "Electromyography reflects the anatomical situation in the muscle parenchyma. Changes in the anatomical structure are present if the normal potential form breaks up into small amplitude or even polyphasic potentials (myopathy type) or increases into high amplitude, broad and coarsely fragmented potentials (chronic neuropathy with regeneration). The caliber and type of muscle fibers are expressed in the speed of conduction. Spontaneous activity suggests an increased excitability of the muscel fibers. Disturbances of neuromuscular transmission are detectable by direct stimulation of the muscle. Analysis of nerve conductivity permits the demonstration of diffuse (polyneuropathy type) or circumscribed (entrapment neuropathy type) nerve affections. The recording of the parameters mentioned is the domain of EMG.", "contents": "[Electromyography as a diagnostic aid (author's transl)]. Electromyography reflects the anatomical situation in the muscle parenchyma. Changes in the anatomical structure are present if the normal potential form breaks up into small amplitude or even polyphasic potentials (myopathy type) or increases into high amplitude, broad and coarsely fragmented potentials (chronic neuropathy with regeneration). The caliber and type of muscle fibers are expressed in the speed of conduction. Spontaneous activity suggests an increased excitability of the muscel fibers. Disturbances of neuromuscular transmission are detectable by direct stimulation of the muscle. Analysis of nerve conductivity permits the demonstration of diffuse (polyneuropathy type) or circumscribed (entrapment neuropathy type) nerve affections. The recording of the parameters mentioned is the domain of EMG."}
{"id": "PMID:197405", "title": "Activation of a procarcinogen to a mutagen by cell-free extracts of anaerobic bacteria.", "content": "The Salmonella mutagenicity assay can be coupled to cell-free preparations derived from anaerobic bacteria (Clostridium perfringens and Bacteroides fragilis) to activate a procarcinogen to a mutagen. This activity is destroyed by heating and by digestion with pronase and it is sensitive to oxygen. These findings indicate that the Salmonella mutagenicity assay can be adapted to the study of the role of anaerobes in the activation of carcinogens.", "contents": "Activation of a procarcinogen to a mutagen by cell-free extracts of anaerobic bacteria. The Salmonella mutagenicity assay can be coupled to cell-free preparations derived from anaerobic bacteria (Clostridium perfringens and Bacteroides fragilis) to activate a procarcinogen to a mutagen. This activity is destroyed by heating and by digestion with pronase and it is sensitive to oxygen. These findings indicate that the Salmonella mutagenicity assay can be adapted to the study of the role of anaerobes in the activation of carcinogens."}
{"id": "PMID:197402", "title": "The cytomegalic inclusion cell and disease; a hypothesis.", "content": "Infections due to human cytomegalovirus are common in the general population, disease on the other hand is rare, being usually associated with the presence of cytomegalic inclusion bearing cells in the tissues. It can be inferred that in healthy individuals latently infected with this agent, such cells are promptly destroyed by the policing immune system and the efficiency of this immune surveillance is due to the high degree of antigenic disparity of cytomegalic inclusion bearing and normal cells. However, any impairment of the immune defence may render the host unable to deal with the inclusion bearing cells, which are then believed to induce at least some of the severe clinical symptoms of cytomegalic inclusion disease.", "contents": "The cytomegalic inclusion cell and disease; a hypothesis. Infections due to human cytomegalovirus are common in the general population, disease on the other hand is rare, being usually associated with the presence of cytomegalic inclusion bearing cells in the tissues. It can be inferred that in healthy individuals latently infected with this agent, such cells are promptly destroyed by the policing immune system and the efficiency of this immune surveillance is due to the high degree of antigenic disparity of cytomegalic inclusion bearing and normal cells. However, any impairment of the immune defence may render the host unable to deal with the inclusion bearing cells, which are then believed to induce at least some of the severe clinical symptoms of cytomegalic inclusion disease."}
{"id": "PMID:197406", "title": "Mutagenic effectiveness and efficiency of sodium azide versus ethyl methanesulfonate in maize: induction of somatic mutations at the yg2 locus by treatment of seeds differing in metabolic state and cell population.", "content": "This study was conducted to compare the effectiveness and efficiency of sodium azide tNaN3) and ethyl methanesulfonate (EMS) for inducing somatic mutations at the yg2 locus in maize seeds of two different metabolic states and cell populations. Dormant or presoaked (72 h at 20 degrees C) seeds heterozygous for yg2 locus were treated with different concentrations of either EMS or NaN3. The cell populations with respect to the percentage of cells in G1, S, G2, and M were also determined for seeds of the two metabolic states. Dormant seeds possessed a higher percentage of cells in G1 and the presoaked seeds a higher percentage of cells in S, G2, and M. The frequency of yg2 sectors in leaves 4 and 5 increased with increasing concentration of both mutagens in both dormant and presoaked seeds. Both mutagens were more effective and efficient in the presoaked seeds. NaN3 was more effective than EMS in terms of number of sectors induced per unit of dose. However, EMS was more efficient as determined by sectors induced per unit of seedling injury and clearly had the ability to induce much higher sector frequencies (more than 10 times greater) than NaN3. The low ability of NaN3 (compared to EMS) to induce mutant sectors may be related to the cells not being treated at the optimum time during the cell cycle, but it is more likely due to its low effectiveness for inducing chromosome aberrations.", "contents": "Mutagenic effectiveness and efficiency of sodium azide versus ethyl methanesulfonate in maize: induction of somatic mutations at the yg2 locus by treatment of seeds differing in metabolic state and cell population. This study was conducted to compare the effectiveness and efficiency of sodium azide tNaN3) and ethyl methanesulfonate (EMS) for inducing somatic mutations at the yg2 locus in maize seeds of two different metabolic states and cell populations. Dormant or presoaked (72 h at 20 degrees C) seeds heterozygous for yg2 locus were treated with different concentrations of either EMS or NaN3. The cell populations with respect to the percentage of cells in G1, S, G2, and M were also determined for seeds of the two metabolic states. Dormant seeds possessed a higher percentage of cells in G1 and the presoaked seeds a higher percentage of cells in S, G2, and M. The frequency of yg2 sectors in leaves 4 and 5 increased with increasing concentration of both mutagens in both dormant and presoaked seeds. Both mutagens were more effective and efficient in the presoaked seeds. NaN3 was more effective than EMS in terms of number of sectors induced per unit of dose. However, EMS was more efficient as determined by sectors induced per unit of seedling injury and clearly had the ability to induce much higher sector frequencies (more than 10 times greater) than NaN3. The low ability of NaN3 (compared to EMS) to induce mutant sectors may be related to the cells not being treated at the optimum time during the cell cycle, but it is more likely due to its low effectiveness for inducing chromosome aberrations."}
{"id": "PMID:197429", "title": "Immunological selection of tumour cells which have lost SV40 antigen expression.", "content": "In an already tumorigenic spontaneously transformed mouse cell, after further transformation by SV40, the virus-specific antigenic function becomes dominant. By transplantation into syngeneic mice SV40 antigen negative revertant tumour cells can be selected out.", "contents": "Immunological selection of tumour cells which have lost SV40 antigen expression. In an already tumorigenic spontaneously transformed mouse cell, after further transformation by SV40, the virus-specific antigenic function becomes dominant. By transplantation into syngeneic mice SV40 antigen negative revertant tumour cells can be selected out."}
{"id": "PMID:197433", "title": "Stimulation of calcium uptake into aortic microsomes by cyclic AMP and cyclic AMP-dependent protein kinase.", "content": "Enhancement of calcium uptake into rabbit aortic microsomes was seen at a cyclic AMP concentration of 10(-6) M in the presence of cyclic AMP-dependent protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37). Protein kinase alone also increased calcium uptake, but cyclic AMP alone was without effect. The results suggest that stimulation of calcium sequestration may be the mechanism of cyclic AMP involvement in vascular smooth muscle relaxation.", "contents": "Stimulation of calcium uptake into aortic microsomes by cyclic AMP and cyclic AMP-dependent protein kinase. Enhancement of calcium uptake into rabbit aortic microsomes was seen at a cyclic AMP concentration of 10(-6) M in the presence of cyclic AMP-dependent protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37). Protein kinase alone also increased calcium uptake, but cyclic AMP alone was without effect. The results suggest that stimulation of calcium sequestration may be the mechanism of cyclic AMP involvement in vascular smooth muscle relaxation."}
{"id": "PMID:197434", "title": "Increased level of cAMP in the rat intestinal mucosa caused by sodium lauryl sulphate.", "content": "The level of cyclic AMP in the jejunal mucosa from tied loops of anaesthetized rats was found to be significantly increased (27-50%) when sodium lauryl sulphate (SLS) was added to the loop fluid (2-27 mM). Imidazole (25 mM) did not significantly alter the resting level of cyclic AMP, but reduced the increase caused by SLS (17 mM). Theophylline (25 mM) significantly increased the intestinal level of cyclic AMP, and potentiated the increase caused by SLS. Ouabain (2.5 mM) did not alter the level of cyclic AMP in the presence or in the absence of SLS. The results of previous experiments on the increases in intestinal absorption caused by SLS or by dibutyryl cyclic AMP (Briseid et al., 1974, 1976) are discussed in light of the present data. It is concluded that the SLS-effect on absorption can only partly by ascribed to its effect on the intestinal level of cyclic AMP.", "contents": "Increased level of cAMP in the rat intestinal mucosa caused by sodium lauryl sulphate. The level of cyclic AMP in the jejunal mucosa from tied loops of anaesthetized rats was found to be significantly increased (27-50%) when sodium lauryl sulphate (SLS) was added to the loop fluid (2-27 mM). Imidazole (25 mM) did not significantly alter the resting level of cyclic AMP, but reduced the increase caused by SLS (17 mM). Theophylline (25 mM) significantly increased the intestinal level of cyclic AMP, and potentiated the increase caused by SLS. Ouabain (2.5 mM) did not alter the level of cyclic AMP in the presence or in the absence of SLS. The results of previous experiments on the increases in intestinal absorption caused by SLS or by dibutyryl cyclic AMP (Briseid et al., 1974, 1976) are discussed in light of the present data. It is concluded that the SLS-effect on absorption can only partly by ascribed to its effect on the intestinal level of cyclic AMP."}
{"id": "PMID:197438", "title": "The induction of tumors in Rana temporaria with nitrosamines.", "content": "Dimethylnitrosamine (DMNA) and diethylnitrosamine (DENA) dissolved in tank water in a dose of 5 and 50 ppm, resp. induced tumors of liver (hepatocellular cancers and adenomas), and of hematopoietic system (hemocytoblastosis). DMNA induced neoplasms in 19 of 43 frogs (44.2%); the average latent period being 18.2 weeks, while DENA induced tumors in 41 of 94 animals (43.6%) within a mean latent period 19.7 weeks. Results of this investigation show the possibility to use anuran amphibians in shorttermed experiments in the study of nitrosocompounds carcinogenicity as well as a biological indicator for environmental pollution.", "contents": "The induction of tumors in Rana temporaria with nitrosamines. Dimethylnitrosamine (DMNA) and diethylnitrosamine (DENA) dissolved in tank water in a dose of 5 and 50 ppm, resp. induced tumors of liver (hepatocellular cancers and adenomas), and of hematopoietic system (hemocytoblastosis). DMNA induced neoplasms in 19 of 43 frogs (44.2%); the average latent period being 18.2 weeks, while DENA induced tumors in 41 of 94 animals (43.6%) within a mean latent period 19.7 weeks. Results of this investigation show the possibility to use anuran amphibians in shorttermed experiments in the study of nitrosocompounds carcinogenicity as well as a biological indicator for environmental pollution."}
{"id": "PMID:197439", "title": "About the influence of halogenated pyrimidines on the in vivo-oncogenesis.", "content": "Reported are in vivo trials on Friend virus-leukemia (FVL), on methylcholanthren-induced fibrosarcomas of the mouse, and on amelanotic melanoma No. 3 of the Syrian hamster after treatment with halogenated pyrimidines, 5'-bromodeoxyuridine (BUDR) and 5'-iododeoxyuridine (IUDR) as to provoke genuine oncorna viruses. Till now, no prove exists that in tissue culture propagated C-type particles are really oncogenic. From the results demonstrated here the conclusion can be drawn that the chosen in vivo-conditions neither oncogens, possibly located in the cells, will be finished to complete oncogenic viruses, nor a spread and multiplication of dormant viruses will take place due to a provocation treatment of the hosts with halogenated pyrimidines. It seems, therefore, that the requirements to activate oncogens in vitro are absolutely different to those needed under in vivo conditions.", "contents": "About the influence of halogenated pyrimidines on the in vivo-oncogenesis. Reported are in vivo trials on Friend virus-leukemia (FVL), on methylcholanthren-induced fibrosarcomas of the mouse, and on amelanotic melanoma No. 3 of the Syrian hamster after treatment with halogenated pyrimidines, 5'-bromodeoxyuridine (BUDR) and 5'-iododeoxyuridine (IUDR) as to provoke genuine oncorna viruses. Till now, no prove exists that in tissue culture propagated C-type particles are really oncogenic. From the results demonstrated here the conclusion can be drawn that the chosen in vivo-conditions neither oncogens, possibly located in the cells, will be finished to complete oncogenic viruses, nor a spread and multiplication of dormant viruses will take place due to a provocation treatment of the hosts with halogenated pyrimidines. It seems, therefore, that the requirements to activate oncogens in vitro are absolutely different to those needed under in vivo conditions."}
{"id": "PMID:197440", "title": "[Computerized axial tomography in the diagnosis of multiple brain tumors-correlation with angiography and nuclear scanning (author's transl)].", "content": "Results of Computerized Axial Tomography with and without intravenous contrast (60% Conray) in 24 patients with multiple brain tumors were analyzed. Of the 24 patients, 19 had metastatic brain tumors, 4 multiple gliomas and 1 patient had multiple meningiomas. Data obtained by C.T. scan were compared to results obtained by angiography and nuclear scanning. In the diagnosis of multiple metastatic brain tumors. C.T. scans were superior to the other two procedures. however, C.T. scanning detected 4 lesions in the case of multiple meningiomas, while angiography disclosed 11 tumors in the same patient. In one patient having multiple gliomas, one (vascular) lesion only was demonstrated by angiography. Many other evaluations of Computerized Axial Tomography have been reported and the advent of this unique non-invasive radiologic technique has resulted in marked changes in the neuro-radiological diagnostic approach to brain tumors. However, it is important to recognize the weak as well as the strong points of each diagnostic procedure including the C.T. scan. At present, in our opinion, even with a positive demonstration of a brain tumor by C.T.scanning, cerebal angiography should be carried out prior to surgical intervention.", "contents": "[Computerized axial tomography in the diagnosis of multiple brain tumors-correlation with angiography and nuclear scanning (author's transl)]. Results of Computerized Axial Tomography with and without intravenous contrast (60% Conray) in 24 patients with multiple brain tumors were analyzed. Of the 24 patients, 19 had metastatic brain tumors, 4 multiple gliomas and 1 patient had multiple meningiomas. Data obtained by C.T. scan were compared to results obtained by angiography and nuclear scanning. In the diagnosis of multiple metastatic brain tumors. C.T. scans were superior to the other two procedures. however, C.T. scanning detected 4 lesions in the case of multiple meningiomas, while angiography disclosed 11 tumors in the same patient. In one patient having multiple gliomas, one (vascular) lesion only was demonstrated by angiography. Many other evaluations of Computerized Axial Tomography have been reported and the advent of this unique non-invasive radiologic technique has resulted in marked changes in the neuro-radiological diagnostic approach to brain tumors. However, it is important to recognize the weak as well as the strong points of each diagnostic procedure including the C.T. scan. At present, in our opinion, even with a positive demonstration of a brain tumor by C.T.scanning, cerebal angiography should be carried out prior to surgical intervention."}
{"id": "PMID:197442", "title": "Comparative in vitro studies on corticotropin releasing activity of vasopressin and hypothalamic median eminence extract.", "content": "The in vitro corticotropic releasing effects of vasopressin (VP) and hypothalamic median eminence (HME) extract were compared as a function of their concentration and preincubation and incubation times. Whereas HME extract augmented the ACTH secretion from non-preincubated adenohypophyses, VP released corticotropin from the pituitaries only after a 2 h preincubation period. The disappearance of endogenous VP during the preincubation time rendered the gland responsive. The maximal stimulation of ACTH secretion by VP was markedly less than that induced by HME extract. The results suggest the presence of VP receptor sites in the anterior pituitary (AP) which are probably different from the receptor sites of the hypothalamic corticotropin releasing factor (CRF).", "contents": "Comparative in vitro studies on corticotropin releasing activity of vasopressin and hypothalamic median eminence extract. The in vitro corticotropic releasing effects of vasopressin (VP) and hypothalamic median eminence (HME) extract were compared as a function of their concentration and preincubation and incubation times. Whereas HME extract augmented the ACTH secretion from non-preincubated adenohypophyses, VP released corticotropin from the pituitaries only after a 2 h preincubation period. The disappearance of endogenous VP during the preincubation time rendered the gland responsive. The maximal stimulation of ACTH secretion by VP was markedly less than that induced by HME extract. The results suggest the presence of VP receptor sites in the anterior pituitary (AP) which are probably different from the receptor sites of the hypothalamic corticotropin releasing factor (CRF)."}
{"id": "PMID:197443", "title": "EEG and task performance after ACTH4-10 in man.", "content": "Effects of the heptapeptide ACTH4-10 (Org OI-63) on EEG, some memory tests, and behavior were examined in 12 normal male volunteers under 30 years of age. An intravenous dose of 60 mg was compared to placebo in a Latin square design. EEG was recorded for 2 h after administration of ACTH4-10 or placebo and was quantified by power spectral density analysis. Drug differences were tested by analyses of variance and covariance. No statistical drug effect was seen on the EEG or behavioral measures. Of the psychological tests, only the digit span test showed a decrease in number of errors with ACTH4-10 (p less than or equal to o.05). These results are consistent with previous studies and suggest that an intravenous bolus of ACTH4-10 has a limited effect on the brain function tested.", "contents": "EEG and task performance after ACTH4-10 in man. Effects of the heptapeptide ACTH4-10 (Org OI-63) on EEG, some memory tests, and behavior were examined in 12 normal male volunteers under 30 years of age. An intravenous dose of 60 mg was compared to placebo in a Latin square design. EEG was recorded for 2 h after administration of ACTH4-10 or placebo and was quantified by power spectral density analysis. Drug differences were tested by analyses of variance and covariance. No statistical drug effect was seen on the EEG or behavioral measures. Of the psychological tests, only the digit span test showed a decrease in number of errors with ACTH4-10 (p less than or equal to o.05). These results are consistent with previous studies and suggest that an intravenous bolus of ACTH4-10 has a limited effect on the brain function tested."}
{"id": "PMID:197444", "title": "ACTH4-10: cognitive and behavioral effects in hyperactive, learning-disabled children.", "content": "A single dose of 30 mg i.m. ACTH4-10 or placebo was given to a sample of 20 hyperactive, learning-disabled children. No significant drug effects were obtained on measures of visual and auditory memory, new learning, impulsivity, attention, perceptual motor skills, anxiety, or behavior during testing. There was a slight increase in pulse rate for drug compared with the placebo group. These findings are in keepeing witth other recent reports of limited or insignificant cognitive effects in adults of a single dose of this peptide.", "contents": "ACTH4-10: cognitive and behavioral effects in hyperactive, learning-disabled children. A single dose of 30 mg i.m. ACTH4-10 or placebo was given to a sample of 20 hyperactive, learning-disabled children. No significant drug effects were obtained on measures of visual and auditory memory, new learning, impulsivity, attention, perceptual motor skills, anxiety, or behavior during testing. There was a slight increase in pulse rate for drug compared with the placebo group. These findings are in keepeing witth other recent reports of limited or insignificant cognitive effects in adults of a single dose of this peptide."}
{"id": "PMID:197445", "title": "Neuroleptics reduce spinal fluid cyclic AMP in schizophrenic patient.", "content": "Cyclic AMP in the cerebrospinal fluid (CSF) was determined in a group of 10 schizophrenic patients before neuroleptic drug treatment and after a mean of 8 week's antipsychotic drug therapy. For 8 patients with marked to moderate treatment response a significant (p less than 0.01) decline in CSF cyclic AMP was observed. This result is consistent with the theory that blockade of postsynaptic dopamine receptors is a major mechanism of the antipsychotic action of neuroleptic drugs.", "contents": "Neuroleptics reduce spinal fluid cyclic AMP in schizophrenic patient. Cyclic AMP in the cerebrospinal fluid (CSF) was determined in a group of 10 schizophrenic patients before neuroleptic drug treatment and after a mean of 8 week's antipsychotic drug therapy. For 8 patients with marked to moderate treatment response a significant (p less than 0.01) decline in CSF cyclic AMP was observed. This result is consistent with the theory that blockade of postsynaptic dopamine receptors is a major mechanism of the antipsychotic action of neuroleptic drugs."}
{"id": "PMID:197446", "title": "ACTH 4-10: a study of toxicological and behavioral effects in an aging sample.", "content": "Placebo and ACTH 4-10 (in ascending dosages from 15 to 60 mg) were administered subcutaneously to normal aging subjects (mean, 65.6 years). Measurements were obtained for EEG, EKG, SMA-12, urine, and blood pressure. Behavioral tasks measuring reaction time (RT), short-term memory, perceptual speed, and motor speed were administered. There were no pre- to post-injection changes in SMA-12, urine, EEG, and EKG. There was an improvement in RT time that was dose related. These data indicate that ACTH 4-10 is (1) safe to administer to an aging population and (2) combined with data on young adults suggest that it may act on the attentional/arousal processes. Results suggest that ACTH 4-10 may have stimulant-like properties on behavior without effecting the CNS and cardiovascular system.", "contents": "ACTH 4-10: a study of toxicological and behavioral effects in an aging sample. Placebo and ACTH 4-10 (in ascending dosages from 15 to 60 mg) were administered subcutaneously to normal aging subjects (mean, 65.6 years). Measurements were obtained for EEG, EKG, SMA-12, urine, and blood pressure. Behavioral tasks measuring reaction time (RT), short-term memory, perceptual speed, and motor speed were administered. There were no pre- to post-injection changes in SMA-12, urine, EEG, and EKG. There was an improvement in RT time that was dose related. These data indicate that ACTH 4-10 is (1) safe to administer to an aging population and (2) combined with data on young adults suggest that it may act on the attentional/arousal processes. Results suggest that ACTH 4-10 may have stimulant-like properties on behavior without effecting the CNS and cardiovascular system."}
{"id": "PMID:197447", "title": "Effect of rubidium, lithium and cesium on brain ATPase and protein kinases.", "content": "The authors studied the effect of rubidium, lithium and cesium on the ATPase system and c-AMP protein kinase in brain. They demonstrated that rubidium could replace potassium in the Na+K-ATPase system, whereas lithium and cesium had no effect on this enzyme activity in the absence of potassium. K+-dependent ATPase was activated by even low rubidium concentrations; lithium and cesium inhibited it. None of three (rubidium, lithium and cesium) affected c-AMP protein kinase.", "contents": "Effect of rubidium, lithium and cesium on brain ATPase and protein kinases. The authors studied the effect of rubidium, lithium and cesium on the ATPase system and c-AMP protein kinase in brain. They demonstrated that rubidium could replace potassium in the Na+K-ATPase system, whereas lithium and cesium had no effect on this enzyme activity in the absence of potassium. K+-dependent ATPase was activated by even low rubidium concentrations; lithium and cesium inhibited it. None of three (rubidium, lithium and cesium) affected c-AMP protein kinase."}
{"id": "PMID:197448", "title": "EEG sleep diagnosis of medical disease in depression.", "content": "The diagnosis of medical disease in the context of a depressive syndrome which may mimic medical illness has traditionally relied on a combination of exhaustive medical screening and neuropsychological testing. When 10 patients with primary depression were compared to 10 patients whose depression occurred in the context of concurrent medical disease, a single EEG sleep variable, total phasic REM activity (RA), correctly identified 95% of all 20 patients as either primary depressives or medical patients with depression. Conventional psychiatric assessment and neuropsychological testing were significantly less powerful discriminators among this sample.", "contents": "EEG sleep diagnosis of medical disease in depression. The diagnosis of medical disease in the context of a depressive syndrome which may mimic medical illness has traditionally relied on a combination of exhaustive medical screening and neuropsychological testing. When 10 patients with primary depression were compared to 10 patients whose depression occurred in the context of concurrent medical disease, a single EEG sleep variable, total phasic REM activity (RA), correctly identified 95% of all 20 patients as either primary depressives or medical patients with depression. Conventional psychiatric assessment and neuropsychological testing were significantly less powerful discriminators among this sample."}
{"id": "PMID:197449", "title": "Computed tomography of intra- and juxtasellar lesions. A radiological study of 108 cases.", "content": "During the first two years with the 160 X 160 matrix EMI scanner at Rigshospitalet, Copenhagen 108 consecutive patients referred with the suspicion of intra- or juxtasellar tumor were subjected to 166 computed tomography (CT) examinations. The X-ray attenuation and contrast enhancement patterns of the various lesions were analyzed. In general, it was difficult to correlate these parameters with the histopathological features. Arachnoid cysts, however, had typical low preinjection attenuation and no contrast enhancement. Chromophobe and eosinophilic pituitary adenomas rarely contained calcium and only in minute amounts, hardly visible on the polaroid pictures. Craniopharyngiomas and low grade suprasellar gliomas frequently contained large calcifications. Grade I gliomas, when located in the optic nerves or hypothalamus, showed significantly higher contrast enhancement than elsewhere in the brain. Three purely intrasellar adenomas were demonstrated with CT only. The diagnostic accuracy of CT was compared to that of carotid angiography, PEG and plain skull films in the lesions verified by initial operation (n = 32). CT gave the highest accuracy of the four methods, but the accuracy of CT differed statistically only from that of carotid angiography.", "contents": "Computed tomography of intra- and juxtasellar lesions. A radiological study of 108 cases. During the first two years with the 160 X 160 matrix EMI scanner at Rigshospitalet, Copenhagen 108 consecutive patients referred with the suspicion of intra- or juxtasellar tumor were subjected to 166 computed tomography (CT) examinations. The X-ray attenuation and contrast enhancement patterns of the various lesions were analyzed. In general, it was difficult to correlate these parameters with the histopathological features. Arachnoid cysts, however, had typical low preinjection attenuation and no contrast enhancement. Chromophobe and eosinophilic pituitary adenomas rarely contained calcium and only in minute amounts, hardly visible on the polaroid pictures. Craniopharyngiomas and low grade suprasellar gliomas frequently contained large calcifications. Grade I gliomas, when located in the optic nerves or hypothalamus, showed significantly higher contrast enhancement than elsewhere in the brain. Three purely intrasellar adenomas were demonstrated with CT only. The diagnostic accuracy of CT was compared to that of carotid angiography, PEG and plain skull films in the lesions verified by initial operation (n = 32). CT gave the highest accuracy of the four methods, but the accuracy of CT differed statistically only from that of carotid angiography."}
{"id": "PMID:197458", "title": "Application of the radioreceptor assay for human chorionic gonadotropin in pregnancy testing  and management of trophoblastic disease.", "content": "A commercially prepared radioreceptor assay (RRA) for human chorionic gonadotropin (hCG) has been evaluated as a pregnancy test and in a quantitative assay to follow patients with hydatidiform mole. The RRA demonstrated almost 100% agreement in comparison with radioimmunoassay (RIA) and urinary hCG tests. In the quantitative assay, a limiting reliable concentration of 70 mIU/ml of hCG in serum could be obtained. Extremely good correlation was achieved between the RRA and RIA test for hCG in 2 patients with hydatidiform mole over a span of 3 months of followup after evacuation of the mole. The usefulness of the RRA as a replacement of RIA tests for hCG is discussed.", "contents": "Application of the radioreceptor assay for human chorionic gonadotropin in pregnancy testing  and management of trophoblastic disease. A commercially prepared radioreceptor assay (RRA) for human chorionic gonadotropin (hCG) has been evaluated as a pregnancy test and in a quantitative assay to follow patients with hydatidiform mole. The RRA demonstrated almost 100% agreement in comparison with radioimmunoassay (RIA) and urinary hCG tests. In the quantitative assay, a limiting reliable concentration of 70 mIU/ml of hCG in serum could be obtained. Extremely good correlation was achieved between the RRA and RIA test for hCG in 2 patients with hydatidiform mole over a span of 3 months of followup after evacuation of the mole. The usefulness of the RRA as a replacement of RIA tests for hCG is discussed."}
{"id": "PMID:197460", "title": "Inhibition of growth of Morris hepatomas 7777 and 7800 by corn oil.", "content": "Intraperitoneal injection of trace amounts of corn oil prior to and following the injection of 40-50 mg of tissue from hepatoma 7777 or 7800 into the thigh of adult male Buffalo rats resulted in a marked decrease in the growth rate of both tumors. Exhaustive extraction of the corn oil with water indicated that the active component was not water soluble. Similar injections of safflower oil or isotonic saline had no effect on tumor growth rate. Analysis of the tissue phospholipid fatty acids revealed that the injected corn oil caused no change in the esterified fatty acids in this lipid fraction.", "contents": "Inhibition of growth of Morris hepatomas 7777 and 7800 by corn oil. Intraperitoneal injection of trace amounts of corn oil prior to and following the injection of 40-50 mg of tissue from hepatoma 7777 or 7800 into the thigh of adult male Buffalo rats resulted in a marked decrease in the growth rate of both tumors. Exhaustive extraction of the corn oil with water indicated that the active component was not water soluble. Similar injections of safflower oil or isotonic saline had no effect on tumor growth rate. Analysis of the tissue phospholipid fatty acids revealed that the injected corn oil caused no change in the esterified fatty acids in this lipid fraction."}
{"id": "PMID:197461", "title": "The use of hybrid cells in immunotherapy.", "content": "HARRIS et. al. isolated somatic hybrid cells (A9/SEWA) between polyoma-induced tumor and mouse fibroblast cell lines. Although these hybrid cells were no longer tumorigenic, we found that their immunogenicity was conserved. It therefore seemed to us that these antigenic, non transplantable, living cells would be an ideal tool for immunotherapy experiments. In our first experiments we assessed the immunoprotection afforded by A9/SEWA cells in both the SEWA tumor/A.SW mouse and C3HPy/C3H mouse systems. However, the efficiency of immunization with hybrid cells is dependent on the stability of the cells, especially in respect to the expression of the TATA. So we also tried to evaluate the immunogenicity as a function of the number of subcultures undergone by the hybrid line. In both systems, the immunogenicity was very good in the early subcultures but, in the C3HPy tumor/C3H mouse system, a loss of immunogenicity was observed as the number of subcultures increased. Thus any clinical application or immunization by hybrid cells would necessitate the verification of the presence of the tumor-associated antigens at each subculture. We are at present experimenting with various in vitro techniques for detection of the expression of these antigens.", "contents": "The use of hybrid cells in immunotherapy. HARRIS et. al. isolated somatic hybrid cells (A9/SEWA) between polyoma-induced tumor and mouse fibroblast cell lines. Although these hybrid cells were no longer tumorigenic, we found that their immunogenicity was conserved. It therefore seemed to us that these antigenic, non transplantable, living cells would be an ideal tool for immunotherapy experiments. In our first experiments we assessed the immunoprotection afforded by A9/SEWA cells in both the SEWA tumor/A.SW mouse and C3HPy/C3H mouse systems. However, the efficiency of immunization with hybrid cells is dependent on the stability of the cells, especially in respect to the expression of the TATA. So we also tried to evaluate the immunogenicity as a function of the number of subcultures undergone by the hybrid line. In both systems, the immunogenicity was very good in the early subcultures but, in the C3HPy tumor/C3H mouse system, a loss of immunogenicity was observed as the number of subcultures increased. Thus any clinical application or immunization by hybrid cells would necessitate the verification of the presence of the tumor-associated antigens at each subculture. We are at present experimenting with various in vitro techniques for detection of the expression of these antigens."}
{"id": "PMID:197462", "title": "Atypical fibrous histiocytoma of the orbit: an electron-microscopic study.", "content": "A young woman developed progressive proptosis of her right eye, accompanied by retinal striae, exposure keratopathy and a severe decrease in visual acuity, reflecting optic neuropathy. An atypical fibrous histiocytoma was found within the orbit. She received orbital exenteration and irradiation. 2 years later she is free of clinical recurrence.", "contents": "Atypical fibrous histiocytoma of the orbit: an electron-microscopic study. A young woman developed progressive proptosis of her right eye, accompanied by retinal striae, exposure keratopathy and a severe decrease in visual acuity, reflecting optic neuropathy. An atypical fibrous histiocytoma was found within the orbit. She received orbital exenteration and irradiation. 2 years later she is free of clinical recurrence."}
{"id": "PMID:197463", "title": "Oral granular-cell tumors. Report of twenty-five cases with electron microscopy.", "content": "Twenty-five cases of granular-cell tumor of the oral cavity are reported. The clinical findings are similar to previously published data. Of five cases studied by electron microscopy, three were processed directly from fresh surgical specimens and two cases were processed following initial formalin fixation. The granules for the most part are morphologically compatible with lysosomes except for a single variety containing viruslike particles. There is increasing evidence in support of a neural origin, but the indications are that more than one cell type may be the progenitor of granular cells of the granular cell tumor.", "contents": "Oral granular-cell tumors. Report of twenty-five cases with electron microscopy. Twenty-five cases of granular-cell tumor of the oral cavity are reported. The clinical findings are similar to previously published data. Of five cases studied by electron microscopy, three were processed directly from fresh surgical specimens and two cases were processed following initial formalin fixation. The granules for the most part are morphologically compatible with lysosomes except for a single variety containing viruslike particles. There is increasing evidence in support of a neural origin, but the indications are that more than one cell type may be the progenitor of granular cells of the granular cell tumor."}
{"id": "PMID:197464", "title": "An ultrastructural study of eosinophilic granuloma: the Langerhans cell--its role in histogenesis and diagnosis.", "content": "An electron microscopic study of a case of eosinophilic granuloma of the mandible was performed. The fine structural similarity between the \"histiocytic\" cells of the lesion and epidermal Langerhans cells is discussed with regard to current theories and information on the origin of Langerhans cells and their potential role in the histogenesis of eosinophilic granuloma and other variants of histiocytosis X.", "contents": "An ultrastructural study of eosinophilic granuloma: the Langerhans cell--its role in histogenesis and diagnosis. An electron microscopic study of a case of eosinophilic granuloma of the mandible was performed. The fine structural similarity between the \"histiocytic\" cells of the lesion and epidermal Langerhans cells is discussed with regard to current theories and information on the origin of Langerhans cells and their potential role in the histogenesis of eosinophilic granuloma and other variants of histiocytosis X."}
{"id": "PMID:197465", "title": "Histogenesis of salivary gland neoplasms.", "content": "In an attempt to explain the histogenesis of salivary gland tumors, a bicellular theory of origin has been presented. This theory is supported by indirect evidence from light and electron microscopy. Two cells, the excretory duct reserve cell and the intercalated duct reserve cell, are presented as the hypothetical cells of origin for salivary gland neoplasms. It is argued that the excretory duct reserve cell gives rise to squamous cell carcinomas and mucoepidermoid carcinomas, and that the intercalated duct reserve cell gives rise to all others. It It is also shown that myoepithelial cells are responsible in part for the wide histologic variation of these neoplasms.", "contents": "Histogenesis of salivary gland neoplasms. In an attempt to explain the histogenesis of salivary gland tumors, a bicellular theory of origin has been presented. This theory is supported by indirect evidence from light and electron microscopy. Two cells, the excretory duct reserve cell and the intercalated duct reserve cell, are presented as the hypothetical cells of origin for salivary gland neoplasms. It is argued that the excretory duct reserve cell gives rise to squamous cell carcinomas and mucoepidermoid carcinomas, and that the intercalated duct reserve cell gives rise to all others. It It is also shown that myoepithelial cells are responsible in part for the wide histologic variation of these neoplasms."}
{"id": "PMID:197470", "title": "[Lipoprotein-x determination in children beyond an age of 6 months (author's transl)].", "content": "In premature and newborn infants an abnormal lipoprotein (LP-X) was almost regularly detectable by examination up to the 24th week after deliver. The aim of the submitted study was to evaluate LP-X results in children older than 6 months. 250 sera of 158 infants of all age groups were tested for presence of LP-X. The frequency of LP-X positive results was 85.7% in the group of infants younger than 24 weeks (91 samples of 45 infants were tested) whereas in the group of infants of an age between 24 weeks and 14 years (159 samples of 113 children were tested) 16.35% positive results were obtained. LP-X positive results showed the same clinical significance in the second group of children as it was demonstrated in adults elsewhere.", "contents": "[Lipoprotein-x determination in children beyond an age of 6 months (author's transl)]. In premature and newborn infants an abnormal lipoprotein (LP-X) was almost regularly detectable by examination up to the 24th week after deliver. The aim of the submitted study was to evaluate LP-X results in children older than 6 months. 250 sera of 158 infants of all age groups were tested for presence of LP-X. The frequency of LP-X positive results was 85.7% in the group of infants younger than 24 weeks (91 samples of 45 infants were tested) whereas in the group of infants of an age between 24 weeks and 14 years (159 samples of 113 children were tested) 16.35% positive results were obtained. LP-X positive results showed the same clinical significance in the second group of children as it was demonstrated in adults elsewhere."}
{"id": "PMID:197475", "title": "Neonatal oncology.", "content": "All known tumor types have been reported in the neonate. A numerical listing and discussion are beyond the scope of this review. Wells and Fraumeni give some insight into common congenital malignant neoplasms. Table 2 lists the percentage of neonatal deaths caused by type-specific cancers. Retinoblastoma is probably the most common malignant tumor in the neonate. About seven per cent of these tumors have been apparent at birth. This tumor is not discussed in either article because it is not lethal until muypes in neonatal and pediatric patients. Some congenital malformations in the in the neonate are recognized as being frankly benign (cysts), potentially malignant (teratomas), and frankly malignant (neuroblastoma). A high percentage of teratomas are benign in the newborn period. Leukemia in the newborn appears to be more aggressive yet neuroblastoma has a better prognosis. More studies are needed to help us define why the neonate does better with some tumors and worse with others. Surface cell markers on neonatal leukemia, B and T cell function studies, and other immunologic surveillance studies are needed. Study of neonatal oncology may add to our knowledge of carcinogenesis and oncogenesis in the future.", "contents": "Neonatal oncology. All known tumor types have been reported in the neonate. A numerical listing and discussion are beyond the scope of this review. Wells and Fraumeni give some insight into common congenital malignant neoplasms. Table 2 lists the percentage of neonatal deaths caused by type-specific cancers. Retinoblastoma is probably the most common malignant tumor in the neonate. About seven per cent of these tumors have been apparent at birth. This tumor is not discussed in either article because it is not lethal until muypes in neonatal and pediatric patients. Some congenital malformations in the in the neonate are recognized as being frankly benign (cysts), potentially malignant (teratomas), and frankly malignant (neuroblastoma). A high percentage of teratomas are benign in the newborn period. Leukemia in the newborn appears to be more aggressive yet neuroblastoma has a better prognosis. More studies are needed to help us define why the neonate does better with some tumors and worse with others. Surface cell markers on neonatal leukemia, B and T cell function studies, and other immunologic surveillance studies are needed. Study of neonatal oncology may add to our knowledge of carcinogenesis and oncogenesis in the future."}
{"id": "PMID:197477", "title": "Hypo-hyperparathyroidism: evidence for a defective parathyroid hormone.", "content": "Biochemical evidence for hypoparathyroidism and roentgenographic evidence for hyperparathyroidism were present in a 7-year-old girl with seizures and tetany. She was hypocalcemic (4.7 mg/dl), hyperphosphatemic (11 mg/dl), and normomagnesemic, with elevated parathyroid hormone level (2,603 pg/dl and 3,693 pg/dl in immunoassays utilizing two different antisera). Somatic features of pseudohypoparathyroidism were absent. Increased serum alkaline phosphatase activity (335 IU/liter) with evidence of subperiosteal bone resorption suggested parathyroid hormone activity on bone. Intramuscular administration of parathyroid extract caused a rise in serum calcium level (9.6 mg/dl) and a fall in serum phosphorus level (7.9 mg/dl). The serum calcium, phosphorus, and alkaline phosphatase activity became normal during vitamin D therapy. Parathyroid hormone values and bone roentgenograms became normal. With serum calcium and phosphorus levels normal, ethylenediaminetetraacetic acid infusion was followed by an increase in plasma parathyroid hormone level but not in urinary cyclic adenosine monophosphate (AMP) or phosphaturia; in contrast, parathyroid extract induced cyclic AMP excretion and phosphaturia. These results suggest that endogenous parathyroid hormone in this patient affects bone resorption but not renal handling of phosphate. We infer that this represents a defective endogenous parathyroid hormone.", "contents": "Hypo-hyperparathyroidism: evidence for a defective parathyroid hormone. Biochemical evidence for hypoparathyroidism and roentgenographic evidence for hyperparathyroidism were present in a 7-year-old girl with seizures and tetany. She was hypocalcemic (4.7 mg/dl), hyperphosphatemic (11 mg/dl), and normomagnesemic, with elevated parathyroid hormone level (2,603 pg/dl and 3,693 pg/dl in immunoassays utilizing two different antisera). Somatic features of pseudohypoparathyroidism were absent. Increased serum alkaline phosphatase activity (335 IU/liter) with evidence of subperiosteal bone resorption suggested parathyroid hormone activity on bone. Intramuscular administration of parathyroid extract caused a rise in serum calcium level (9.6 mg/dl) and a fall in serum phosphorus level (7.9 mg/dl). The serum calcium, phosphorus, and alkaline phosphatase activity became normal during vitamin D therapy. Parathyroid hormone values and bone roentgenograms became normal. With serum calcium and phosphorus levels normal, ethylenediaminetetraacetic acid infusion was followed by an increase in plasma parathyroid hormone level but not in urinary cyclic adenosine monophosphate (AMP) or phosphaturia; in contrast, parathyroid extract induced cyclic AMP excretion and phosphaturia. These results suggest that endogenous parathyroid hormone in this patient affects bone resorption but not renal handling of phosphate. We infer that this represents a defective endogenous parathyroid hormone."}
{"id": "PMID:197478", "title": "Hospital-acquired viral respiratory illness on a pediatric ward.", "content": "All 171 patients admitted to four study rooms containing cribs were under surveillance during the winter and spring for development of nosocomial respiratory and infection. One sixth of the 90 children at risk acquired respiratory illness while in the hospital. Viruses were isolated from two thirds of the patients with nosocomial infections: rhinovirus, respiratory syncytial virus, parainfluenza, and influenza A and B. Serial viral cultures of the children under surveillance suggested that nine of 11 virus-positive nosocomial infections were not acquired from a roommate. Furthermore, the risk to a patient of becoming infected with a virus being shed by a roommate was only 3%. The need for isolation of all children with respiratory illness in a single room with a separate air exhaust system is not suggested by these data.", "contents": "Hospital-acquired viral respiratory illness on a pediatric ward. All 171 patients admitted to four study rooms containing cribs were under surveillance during the winter and spring for development of nosocomial respiratory and infection. One sixth of the 90 children at risk acquired respiratory illness while in the hospital. Viruses were isolated from two thirds of the patients with nosocomial infections: rhinovirus, respiratory syncytial virus, parainfluenza, and influenza A and B. Serial viral cultures of the children under surveillance suggested that nine of 11 virus-positive nosocomial infections were not acquired from a roommate. Furthermore, the risk to a patient of becoming infected with a virus being shed by a roommate was only 3%. The need for isolation of all children with respiratory illness in a single room with a separate air exhaust system is not suggested by these data."}
{"id": "PMID:197482", "title": "Calcium ion uptake induced by cholinergic and alpha-adrenergic stimulation in isolated cells of rat salivary glands.", "content": "Adrenaline (10(-5) M) and carbamylcholine (10(-4) M) stimulate 45Ca2+ uptake into isolated cells of rat submandibular galnd and parotid glands. In the presence of the alpha-adrenoreceptor blocking agent phentolamine, adrenaline stimulation of 45Ca2+ uptake is abolished. The beta-adrenergic stimulant isoproterenol has no effect on 45Ca2+ uptake. Carbamylcholine induced 45Ca2+ uptake is inhibited by atropine. The Ca2+ ionophore A23187 stimulates 45Ca2+ uptake, whereas dibutyryl cyclic adenosine 3',5'-monophosphate and dibutyryl cyclic guanosine 3',5'-monophosphate have no effect on 45Ca2+ uptake. A graphical analysis of the 45Ca2+ uptake curves reveals at least two phases: a fast phase and a slow phase, both of which are stimulated by adrenaline and carbamylcholine. The 45Ca-exchangeable pool size is increased by adrenaline and carbamylcholine in both the fast and the slow phases. These results suggest that alpha-adrenergic and cholinergic agonists act by increasing the rate of Ca2+ transfer into the cells of the parotid and submandibular salivary glands most probably through an increase of the cell membrane permeability for Ca2+.", "contents": "Calcium ion uptake induced by cholinergic and alpha-adrenergic stimulation in isolated cells of rat salivary glands. Adrenaline (10(-5) M) and carbamylcholine (10(-4) M) stimulate 45Ca2+ uptake into isolated cells of rat submandibular galnd and parotid glands. In the presence of the alpha-adrenoreceptor blocking agent phentolamine, adrenaline stimulation of 45Ca2+ uptake is abolished. The beta-adrenergic stimulant isoproterenol has no effect on 45Ca2+ uptake. Carbamylcholine induced 45Ca2+ uptake is inhibited by atropine. The Ca2+ ionophore A23187 stimulates 45Ca2+ uptake, whereas dibutyryl cyclic adenosine 3',5'-monophosphate and dibutyryl cyclic guanosine 3',5'-monophosphate have no effect on 45Ca2+ uptake. A graphical analysis of the 45Ca2+ uptake curves reveals at least two phases: a fast phase and a slow phase, both of which are stimulated by adrenaline and carbamylcholine. The 45Ca-exchangeable pool size is increased by adrenaline and carbamylcholine in both the fast and the slow phases. These results suggest that alpha-adrenergic and cholinergic agonists act by increasing the rate of Ca2+ transfer into the cells of the parotid and submandibular salivary glands most probably through an increase of the cell membrane permeability for Ca2+."}
{"id": "PMID:197483", "title": "Determination of oxytetracycline induced fluorescence and autofluorescence as an indicator of age and sex differences in rat femur.", "content": "Simple and rapid methods for the determination and detection of autofluorescence and oxytetracycline (OTC) induced fluorescence in powdered and intact bone (without previous chemical extraction of the antibiotic) were used to estimate age and sex related differences in the rat femur. The autofluorescence always had collagen characteristics; it increased with age and was not sex dependent. The intensity of OTC induced fluorescence decreased with age, being higher in males than in females. In the oldest animals, however a slight increase in the fluorescence intensity was observed, and sex differences disappeared. The spectrofluorometric measurements of intact femora indicate a higher OTC retention on the bone surface of young animals and adult males but not in adult females. The results indicate that the determination of OTC retention in the bone using our quantitative fluorometric method and the detection of OTC deposition at bone surface using a spectrofluorometric technique can be a sensitive and inexpensive tool for experimental studies of bone changes in physiological and pathological conditions.", "contents": "Determination of oxytetracycline induced fluorescence and autofluorescence as an indicator of age and sex differences in rat femur. Simple and rapid methods for the determination and detection of autofluorescence and oxytetracycline (OTC) induced fluorescence in powdered and intact bone (without previous chemical extraction of the antibiotic) were used to estimate age and sex related differences in the rat femur. The autofluorescence always had collagen characteristics; it increased with age and was not sex dependent. The intensity of OTC induced fluorescence decreased with age, being higher in males than in females. In the oldest animals, however a slight increase in the fluorescence intensity was observed, and sex differences disappeared. The spectrofluorometric measurements of intact femora indicate a higher OTC retention on the bone surface of young animals and adult males but not in adult females. The results indicate that the determination of OTC retention in the bone using our quantitative fluorometric method and the detection of OTC deposition at bone surface using a spectrofluorometric technique can be a sensitive and inexpensive tool for experimental studies of bone changes in physiological and pathological conditions."}
{"id": "PMID:197487", "title": "[Erythrocyte membrane protein abnormalities in hereditary hemolytic anemias].", "content": "The structural and functional abnormalities of erythrocyte membrane proteins in hereditary hemolytic anemias are reviewed. The authors stress the problems of protein solubilization and the artefacts of the sodium dodecylsulphate polyacrylamide gel electrophoresis; protein abnormalities observed with that method are inconstant and non-specific. Abnormal \"spectrin\" has been reported in hereditary spherocytosis: however analysis of purified spectrin peptides by isoelectric focusing in 8M urea did not reveal any difference between normal and hereditary spherocytosis spectrin. Deficient autophosphorylation of erythrocyte membrane proteins by endogenous membrane protein-kinases 3'5-cyclic-AMP dependent and independent was pointed out in hereditary spherocytosis and stomatocytosis: the authors' experience was contrary to such results: quantitatively and qualitatively normal activity of membrane protein-kinase was found in five cases of hereditary spherocytosis. The authenticity, frequency and specificity of the various membrane protein abnormalities reported so far, are not firmly established. Many insufficiently verified results published prematurely have been later denied. To date no membrane protein anomaly may be considered as a biochemical cause of any type of hereditary hemolytic anemia.", "contents": "[Erythrocyte membrane protein abnormalities in hereditary hemolytic anemias]. The structural and functional abnormalities of erythrocyte membrane proteins in hereditary hemolytic anemias are reviewed. The authors stress the problems of protein solubilization and the artefacts of the sodium dodecylsulphate polyacrylamide gel electrophoresis; protein abnormalities observed with that method are inconstant and non-specific. Abnormal \"spectrin\" has been reported in hereditary spherocytosis: however analysis of purified spectrin peptides by isoelectric focusing in 8M urea did not reveal any difference between normal and hereditary spherocytosis spectrin. Deficient autophosphorylation of erythrocyte membrane proteins by endogenous membrane protein-kinases 3'5-cyclic-AMP dependent and independent was pointed out in hereditary spherocytosis and stomatocytosis: the authors' experience was contrary to such results: quantitatively and qualitatively normal activity of membrane protein-kinase was found in five cases of hereditary spherocytosis. The authenticity, frequency and specificity of the various membrane protein abnormalities reported so far, are not firmly established. Many insufficiently verified results published prematurely have been later denied. To date no membrane protein anomaly may be considered as a biochemical cause of any type of hereditary hemolytic anemia."}
{"id": "PMID:197488", "title": "The problems of eukaryotic and prokaryotic DNA packaging and in vivo conformation posed by superhelix density heterogeneity.", "content": "Systems for gel electrophoresis in the presence of one of the intercalative unwinding ligands, ethidium or chloroquine, have been developed which permit the resolution of highly supercoiled closed circular DNA molecules differing by unit values of the topological winding number, alpha. All native closed circular DNAs examined, including the viral and intracellular forms of SV40 and polyoma DNA, bacterial plasmid DNAs, and the double stranded closed circular DNA genome of the marine bacteriophage, PM2, are more heterogeneous with respect to the number of superhelical turns present than are the thermal distributions observed in the limit products of the action of nicking-closing (N-C) enzyme on the respective DNAs. In the cases of SV40 and polyoma, where it has been shown that the supercoiling is a combined consequence of the binding of the four nucleosomal histones, H2a, H2b, H3 and H4, and the action of N-C enzyme, the breadth of the distributions within the form I DNAs poses specific problems since the work of other laboratories indicates that the number of nucleosomes on the respective minichromosomes falls within a narrow distribution of 21. If it is assumed that all nucleosomes have identical structures, and that the DNA within a nucleosome is not free to rotate, the native DNA would be anticipated to be less heterogeneous than the thermal equilibrium mixtures present in N-C enzyme relaxed SV40 and polyoma DNAs. The absolute number of superhelical turns (at 37 degrees C in 0.2 M NaCl) in virion polyoma DNA has been determined to be 26 +/- 1, which is the same value obtained for virion SV40 DNA. This is consistent with the observations that polyoma DNA has a higher molecular weight, a lower superhelix density, but the same number of nucleosomes as SV40 DNA. In addition, the distributions within the virion and intracellular form I DNAs of both SV40 and polyoma were found to be indistinguishable.Images", "contents": "The problems of eukaryotic and prokaryotic DNA packaging and in vivo conformation posed by superhelix density heterogeneity. Systems for gel electrophoresis in the presence of one of the intercalative unwinding ligands, ethidium or chloroquine, have been developed which permit the resolution of highly supercoiled closed circular DNA molecules differing by unit values of the topological winding number, alpha. All native closed circular DNAs examined, including the viral and intracellular forms of SV40 and polyoma DNA, bacterial plasmid DNAs, and the double stranded closed circular DNA genome of the marine bacteriophage, PM2, are more heterogeneous with respect to the number of superhelical turns present than are the thermal distributions observed in the limit products of the action of nicking-closing (N-C) enzyme on the respective DNAs. In the cases of SV40 and polyoma, where it has been shown that the supercoiling is a combined consequence of the binding of the four nucleosomal histones, H2a, H2b, H3 and H4, and the action of N-C enzyme, the breadth of the distributions within the form I DNAs poses specific problems since the work of other laboratories indicates that the number of nucleosomes on the respective minichromosomes falls within a narrow distribution of 21. If it is assumed that all nucleosomes have identical structures, and that the DNA within a nucleosome is not free to rotate, the native DNA would be anticipated to be less heterogeneous than the thermal equilibrium mixtures present in N-C enzyme relaxed SV40 and polyoma DNAs. The absolute number of superhelical turns (at 37 degrees C in 0.2 M NaCl) in virion polyoma DNA has been determined to be 26 +/- 1, which is the same value obtained for virion SV40 DNA. This is consistent with the observations that polyoma DNA has a higher molecular weight, a lower superhelix density, but the same number of nucleosomes as SV40 DNA. In addition, the distributions within the virion and intracellular form I DNAs of both SV40 and polyoma were found to be indistinguishable.Images"}
{"id": "PMID:197489", "title": "The photoinactivation of an RNA animal virus, vesicular stomatitis virus, with the aid of newly synthesized psoralen derivatives.", "content": "The newly synthesized psoralen derivatives, 4' hydroxymethyl 4,5',8 trimethylpsoralen, 4' methoxymethyl 4,5',8 trimethylpsoralen, and 4' aminomethyl 4,5',8 trimethylpsoralen hydrochloride photoreact with the single-stranded RNA animal virus, Vesicular Stomatitis virus, VSV. This virus is inactivated 10(3) times more effectively by photoreaction with these compounds than when photoreacted with 4,5',8 trimethylpsoralen. Under these conditions the RNA virus remains more than 10(3) times less sensitive to inactivation by these new photoreagents than were two double-stranded DNA viruses, Herpes Simplex type 2 (HSV-2) and Vaccinia. Preliminary evidence for the generality of this result is discussed.", "contents": "The photoinactivation of an RNA animal virus, vesicular stomatitis virus, with the aid of newly synthesized psoralen derivatives. The newly synthesized psoralen derivatives, 4' hydroxymethyl 4,5',8 trimethylpsoralen, 4' methoxymethyl 4,5',8 trimethylpsoralen, and 4' aminomethyl 4,5',8 trimethylpsoralen hydrochloride photoreact with the single-stranded RNA animal virus, Vesicular Stomatitis virus, VSV. This virus is inactivated 10(3) times more effectively by photoreaction with these compounds than when photoreacted with 4,5',8 trimethylpsoralen. Under these conditions the RNA virus remains more than 10(3) times less sensitive to inactivation by these new photoreagents than were two double-stranded DNA viruses, Herpes Simplex type 2 (HSV-2) and Vaccinia. Preliminary evidence for the generality of this result is discussed."}
{"id": "PMID:197490", "title": "Strandedness of newly synthesized short pieces of polyoma DNA from isolated nuclei.", "content": "The discontinuous synthesis of the complementary strands of polyoma DNA in isolated nuclei has been studied by hybridization techniques. The relative amounts of the newly synthesized complementary strands were compared by separately annealing them to denatured HpaII restriction fragments. In every case an excess (1.4- to 2.4-fold) of short pieces of the strand growing in the 3' leads to 5' direction was found.", "contents": "Strandedness of newly synthesized short pieces of polyoma DNA from isolated nuclei. The discontinuous synthesis of the complementary strands of polyoma DNA in isolated nuclei has been studied by hybridization techniques. The relative amounts of the newly synthesized complementary strands were compared by separately annealing them to denatured HpaII restriction fragments. In every case an excess (1.4- to 2.4-fold) of short pieces of the strand growing in the 3' leads to 5' direction was found."}
{"id": "PMID:197491", "title": "Polyoma-induced stimulation of cellular RNA synthesis is paralleled by changed expression of the viral genome.", "content": "We studied synthesis of viral and cellular RNA in the presence and absence of 5-fluorodeoxyuridine (FdU, an inhibitor of DNA synthesis) during lytic infection with polyoma virus in confluent, primary mouse kidney cell cultures. In the presence of FdU, synthesis of early 19S polyoma mRNA and of polyoma tumor (T)-antigen, i.e. expression of the early viral gene, is rapidly followed by a mitogenic reaction of the host cell; it leads to an increase of 30 +/- 5% in cellular, mainly 28S and 18S rRNA, followed by activation of the cellular DNA-synthesizing apparatus. Polyoma-induced cellular RNA synthesis is paralleled by increased production of early 19S mRNA and begin of expression of the late viral genes, leading to synthesis of small amounts of late 19S and 16S mRNAs. Changed expression of the viral genome occurs in the absence of detectable synthesis of polyoma DNA I. Infection in the absence of FdU induces the same sequence of events; it is followed, however, by duplication of the mouse cell chromatin (S-phase) and production of  progeny virus.", "contents": "Polyoma-induced stimulation of cellular RNA synthesis is paralleled by changed expression of the viral genome. We studied synthesis of viral and cellular RNA in the presence and absence of 5-fluorodeoxyuridine (FdU, an inhibitor of DNA synthesis) during lytic infection with polyoma virus in confluent, primary mouse kidney cell cultures. In the presence of FdU, synthesis of early 19S polyoma mRNA and of polyoma tumor (T)-antigen, i.e. expression of the early viral gene, is rapidly followed by a mitogenic reaction of the host cell; it leads to an increase of 30 +/- 5% in cellular, mainly 28S and 18S rRNA, followed by activation of the cellular DNA-synthesizing apparatus. Polyoma-induced cellular RNA synthesis is paralleled by increased production of early 19S mRNA and begin of expression of the late viral genes, leading to synthesis of small amounts of late 19S and 16S mRNAs. Changed expression of the viral genome occurs in the absence of detectable synthesis of polyoma DNA I. Infection in the absence of FdU induces the same sequence of events; it is followed, however, by duplication of the mouse cell chromatin (S-phase) and production of  progeny virus."}
{"id": "PMID:197492", "title": "In vitro transcription of herpes simplex virus ANG DNA by E-coli RNA polymerase.", "content": "HSV-1 ANG DNA and a defective genome of the same virus were transcribed with E. coli RNA polymerase under various salt conditions. The extent of transcription was assayed by hybridizing the cRNA to the Hind III, Hpa I and Hind II restriction fragments of the DNA templates using the blot technique of E. Southern. The transcripts proved to contain sequences homologous to all DNA fragments. A similar ratio of hybridized cRNA and the amount of fragment DNA was observed in all cases. The results suggest that both, the wt and the defective HSV ANG genome were completely transcribed.", "contents": "In vitro transcription of herpes simplex virus ANG DNA by E-coli RNA polymerase. HSV-1 ANG DNA and a defective genome of the same virus were transcribed with E. coli RNA polymerase under various salt conditions. The extent of transcription was assayed by hybridizing the cRNA to the Hind III, Hpa I and Hind II restriction fragments of the DNA templates using the blot technique of E. Southern. The transcripts proved to contain sequences homologous to all DNA fragments. A similar ratio of hybridized cRNA and the amount of fragment DNA was observed in all cases. The results suggest that both, the wt and the defective HSV ANG genome were completely transcribed."}
{"id": "PMID:197493", "title": "Relaxed circular SV40 DNA as cleavage intermediate of two restriction endonucleases.", "content": "We have determined the mode of cleavage of superhelical SV40 DNA (Form I) by restriction endonucleases EcoRI and HpaII at 37 degrees C. By analysis with agarose gel electrophoresis and direct examination with dark field electron microscopy, we found that a large amount of the single-nicked circular DNA (Form II) was produced before the linear SV40 DNA (Form III) appeared. Thus, both restriction enzymes cleave only one strand of the superhelical DNA first. The second cleavage on the complementary strand occurred after a lag period. The first order rate constant for the second cleavage by EcoRI endonuclease was determined and a kinetic reaction scheme for both enzymes is proposed.", "contents": "Relaxed circular SV40 DNA as cleavage intermediate of two restriction endonucleases. We have determined the mode of cleavage of superhelical SV40 DNA (Form I) by restriction endonucleases EcoRI and HpaII at 37 degrees C. By analysis with agarose gel electrophoresis and direct examination with dark field electron microscopy, we found that a large amount of the single-nicked circular DNA (Form II) was produced before the linear SV40 DNA (Form III) appeared. Thus, both restriction enzymes cleave only one strand of the superhelical DNA first. The second cleavage on the complementary strand occurred after a lag period. The first order rate constant for the second cleavage by EcoRI endonuclease was determined and a kinetic reaction scheme for both enzymes is proposed."}
{"id": "PMID:197494", "title": "A method for the isolation of cross-linked nucleosides from DNA: application to cross-links induced by nitrous acid.", "content": "A procedure is reported for the isolation of cross-linked nucleosides from nitrous acid-treated calf thymus DNA. Cross-linked DNA was hydrolyzed enzymatically with deoxyribonuclease I and snake venom phosphodiesterase and fractionated on a DEAE-Sephadex column. After desalting, the fractions were characterized by ultraviolet spectroscopy, anion exchange high pressure liquid chromatography, gel filtration, and two dimensional thin layer chromatography. A cross-linked dinucleotide, and a series of oligonucleotides were isolated. The oligomers, which had resisted digestion by the above enzyme system, were digested to the nucleoside level by a spleen phosphodiesterase-alkaline phosphatase combination. A second cross-linked product was isolated from this mixture. The cross-linked nucleosides were less than 0.17% of the total nucleotides of the DNA. The methods developed here are recommended for the isolation of products from DNA treated with other cross-linking agents.", "contents": "A method for the isolation of cross-linked nucleosides from DNA: application to cross-links induced by nitrous acid. A procedure is reported for the isolation of cross-linked nucleosides from nitrous acid-treated calf thymus DNA. Cross-linked DNA was hydrolyzed enzymatically with deoxyribonuclease I and snake venom phosphodiesterase and fractionated on a DEAE-Sephadex column. After desalting, the fractions were characterized by ultraviolet spectroscopy, anion exchange high pressure liquid chromatography, gel filtration, and two dimensional thin layer chromatography. A cross-linked dinucleotide, and a series of oligonucleotides were isolated. The oligomers, which had resisted digestion by the above enzyme system, were digested to the nucleoside level by a spleen phosphodiesterase-alkaline phosphatase combination. A second cross-linked product was isolated from this mixture. The cross-linked nucleosides were less than 0.17% of the total nucleotides of the DNA. The methods developed here are recommended for the isolation of products from DNA treated with other cross-linking agents."}
{"id": "PMID:197495", "title": "The specificity of S1 nuclease toward RNA-DNA hybrids as studied using isotopes of phosphorus-32 and phosphorus-33.", "content": "Hybrids were formed from Bacillus cereus DNA and ribosomal RNA. They were treated with various combination of S1 nuclease and ribonuclease, and the molar ratios of the RNA and DNA moieties remaining in the treated hybrids were determined using a 32P-33P dual-label technique. It was found that both S1 nuclease and ribonuclease are required to give hybrid with RNA and DNA in a perfect 1:1 molar ratio. It was noted that the dual-label technique which employs orthophosphate as the sole phosphorus source for both labels gives unambiguous molar ratios and obviates the need to calculate specific activities, make quench corrections, or correct for base content.", "contents": "The specificity of S1 nuclease toward RNA-DNA hybrids as studied using isotopes of phosphorus-32 and phosphorus-33. Hybrids were formed from Bacillus cereus DNA and ribosomal RNA. They were treated with various combination of S1 nuclease and ribonuclease, and the molar ratios of the RNA and DNA moieties remaining in the treated hybrids were determined using a 32P-33P dual-label technique. It was found that both S1 nuclease and ribonuclease are required to give hybrid with RNA and DNA in a perfect 1:1 molar ratio. It was noted that the dual-label technique which employs orthophosphate as the sole phosphorus source for both labels gives unambiguous molar ratios and obviates the need to calculate specific activities, make quench corrections, or correct for base content."}
{"id": "PMID:197496", "title": "Salt and divalent cations affect the flexible nature of the natural beaded chromatin structure.", "content": "A natural chromatin containing simian virus 40 (SV40) DNA and histone has been used to examine changes in chromatin structure caused by various physical and chemical treatments. We find that histone H1 depleted chromatin is more compact in solutions of 0.15M NaCl or 2 mM MgCl2 than in 0.01 M NaCl or 0.6M NaCL, and is compact in 0.01 M NaCl solutions if histone H 1 is present. Even high concentrations of urea did not alter the fundamental beaded structure, consisting of 110A beads of 200 base pair content, each joined by thin DNA bridges of 50 base pairs. The physical bead observed by EM therefore contains more DNA than the 140 base pair \"core particle\". The natural variation in the bridge length is consistent with the broad bands observed after nuclease digestion of chromatin. Chromatin prepared for EM without fixation containing long 20A to 30A fibers possibly complexed with protein.", "contents": "Salt and divalent cations affect the flexible nature of the natural beaded chromatin structure. A natural chromatin containing simian virus 40 (SV40) DNA and histone has been used to examine changes in chromatin structure caused by various physical and chemical treatments. We find that histone H1 depleted chromatin is more compact in solutions of 0.15M NaCl or 2 mM MgCl2 than in 0.01 M NaCl or 0.6M NaCL, and is compact in 0.01 M NaCl solutions if histone H 1 is present. Even high concentrations of urea did not alter the fundamental beaded structure, consisting of 110A beads of 200 base pair content, each joined by thin DNA bridges of 50 base pairs. The physical bead observed by EM therefore contains more DNA than the 140 base pair \"core particle\". The natural variation in the bridge length is consistent with the broad bands observed after nuclease digestion of chromatin. Chromatin prepared for EM without fixation containing long 20A to 30A fibers possibly complexed with protein."}
{"id": "PMID:197497", "title": "Escherichia coli DNA synthesis in vitro: insensitivity of ATP-dependent DNA repair to inhibition by novobiocin.", "content": "Novobiocin, an effective inhibitor of DNA replicaion in Escherichia coli, is shown to have no effect on the ATP-dependent DNA repair carried out by toluenized cells after ultraviolet irradiation. Therefore novobiocin can be considered a selective inhibitor of replicative DNA synthesis in vitro.", "contents": "Escherichia coli DNA synthesis in vitro: insensitivity of ATP-dependent DNA repair to inhibition by novobiocin. Novobiocin, an effective inhibitor of DNA replicaion in Escherichia coli, is shown to have no effect on the ATP-dependent DNA repair carried out by toluenized cells after ultraviolet irradiation. Therefore novobiocin can be considered a selective inhibitor of replicative DNA synthesis in vitro."}
{"id": "PMID:197498", "title": "Kinetics of various 99mTc-Sn-pyrophosphate compounds in the rat. I. In vivo studies.", "content": "The kinetic data of two different 99mTc-Sn-pyrophosphate compounds (compound A and B) were evaluated in non-adult rats. Only compound A concentrated in bone. Both compounds dispersed rapidly in the intravascular as well as the extravascular space. The plasma protein bond of both compounds increased with time after injection and impaired both the renal clearance of both compounds and the bone clearance of compound A. The renal clearance of both compounds was somewhat above that of 51Cr-EDTA. It is concluded that compound A and B is mainly excreted by glomerular filtration. About one fourth of the glomerular filtrate of compound B is reabsorbed and accumulated by the tubular cells.", "contents": "Kinetics of various 99mTc-Sn-pyrophosphate compounds in the rat. I. In vivo studies. The kinetic data of two different 99mTc-Sn-pyrophosphate compounds (compound A and B) were evaluated in non-adult rats. Only compound A concentrated in bone. Both compounds dispersed rapidly in the intravascular as well as the extravascular space. The plasma protein bond of both compounds increased with time after injection and impaired both the renal clearance of both compounds and the bone clearance of compound A. The renal clearance of both compounds was somewhat above that of 51Cr-EDTA. It is concluded that compound A and B is mainly excreted by glomerular filtration. About one fourth of the glomerular filtrate of compound B is reabsorbed and accumulated by the tubular cells."}
{"id": "PMID:197499", "title": "Bone-to-bone, joint-to-bone and joint-to-joint ratios in normal and diseased skeletal states using region-of-interest technique and bone-seeking radiopharmaceuticals.", "content": "Bone-to-bone, iliosacral joint-to-os sacrum and joint-to-joint ratios were computed using the region-of-interest technique 2 to 3 hrs. after injection of 99mTc Sn-methylene-diphosphonate or 99mTc Sn-pyrophosphate in 139 patients with skeletal diseases (bone tumours, degenerative changes of the spine and joints, inflammatory changes of joints) as well as in 123 patients with normal skeletal states. In the latter group, iliosacral joint-to-os sacrum ratios decreased with increasing age of the patients. In patients with osseous metastases of the spine ratios of 0.80 to 4.0 occurred ( reference area second vertebra below or above the affected vertebra). In degenerative changes of the spine values of 0.80 to 1.69 were computed. These results show, that 74% of the spine metastases could not be differentiated from benign changes of the spine by determining their relative amounts of bone uptake. In bone tumours of the extremities and in rheumatoid or gouty arthritis of the small joints (hands and feet) the highest ratios, i.e. contrasts, occurred referring to a contralateral reference area. Osteoarthritic and inflammatory alterations of the big joints could not be differentiated because of percentual distribution of the increased joint-to-joint ratios turned out to be nearly identical.", "contents": "Bone-to-bone, joint-to-bone and joint-to-joint ratios in normal and diseased skeletal states using region-of-interest technique and bone-seeking radiopharmaceuticals. Bone-to-bone, iliosacral joint-to-os sacrum and joint-to-joint ratios were computed using the region-of-interest technique 2 to 3 hrs. after injection of 99mTc Sn-methylene-diphosphonate or 99mTc Sn-pyrophosphate in 139 patients with skeletal diseases (bone tumours, degenerative changes of the spine and joints, inflammatory changes of joints) as well as in 123 patients with normal skeletal states. In the latter group, iliosacral joint-to-os sacrum ratios decreased with increasing age of the patients. In patients with osseous metastases of the spine ratios of 0.80 to 4.0 occurred ( reference area second vertebra below or above the affected vertebra). In degenerative changes of the spine values of 0.80 to 1.69 were computed. These results show, that 74% of the spine metastases could not be differentiated from benign changes of the spine by determining their relative amounts of bone uptake. In bone tumours of the extremities and in rheumatoid or gouty arthritis of the small joints (hands and feet) the highest ratios, i.e. contrasts, occurred referring to a contralateral reference area. Osteoarthritic and inflammatory alterations of the big joints could not be differentiated because of percentual distribution of the increased joint-to-joint ratios turned out to be nearly identical."}
{"id": "PMID:197500", "title": "[Retention and dosage in radiation synovectomy with yttrium-90-silicate colloid].", "content": "Investigations on patients and on phantoms were performed to determine the retention and the absorbed dose in radiation synovectomy with 90Y silicate colloid. The electrons of 90Y are totally absorbed within the surrounding tissue and produce bremsstrahlung with a maximum intensity at about 110 keV. After application of 6 mCi 90Y the dose rate of the bremsstrahlung was measured at a distance of 10 cm over 13 knees in a total of 10 patients and was found to range between 0.6 and 1.3 mR/h. During a period of 3 hours up to 3 days after injection practically no removal of the material from the joint was observed. According to approximative calculations the mean dose absorbed in the knee ranged between 3650 and 7300 rad, and the absorbed dose in the synovium between 5500 and 11000 rad.", "contents": "[Retention and dosage in radiation synovectomy with yttrium-90-silicate colloid]. Investigations on patients and on phantoms were performed to determine the retention and the absorbed dose in radiation synovectomy with 90Y silicate colloid. The electrons of 90Y are totally absorbed within the surrounding tissue and produce bremsstrahlung with a maximum intensity at about 110 keV. After application of 6 mCi 90Y the dose rate of the bremsstrahlung was measured at a distance of 10 cm over 13 knees in a total of 10 patients and was found to range between 0.6 and 1.3 mR/h. During a period of 3 hours up to 3 days after injection practically no removal of the material from the joint was observed. According to approximative calculations the mean dose absorbed in the knee ranged between 3650 and 7300 rad, and the absorbed dose in the synovium between 5500 and 11000 rad."}
{"id": "PMID:197501", "title": "[Comparison of scintigraphic and neurosurgical findings in brain tumors].", "content": "In 120 cases of operated brain tumors the neurosurgical findings are compared with the results of brain scintigraphy with 99mTc-pertechnetate. The study comprises only the frequent types of brain tumors such as meningeoma, astrozytoma, glioblastoma, oligodendroglioma, neurinoma and metastases. From the neurosurgical findinds were evaluated the localisation and size of the tumor, the extent of vascularity, of cysts and necroses. These data were related to the type or radioangiography and the degree of uptake in the scintigraphy. The tumors could be demonstrated by scintigraphy in 105 of the cases. Radioangiography was obviously superior to late scintigraphy in the diagnosis of the type of tumor. The size of the tumor appeared in the meningeomas greater and in the other types of tumor smaller than found by operation. The uptake in scintigraphy showed a correlation to vascularity. Otherwise there was found no correlation between vascularity and type of radioangiography in glioblastomas. This surprising result needs further investigatiion. Half of the cases with cysts and necroses showed an inhomogeneity in the uptake by the tumor.", "contents": "[Comparison of scintigraphic and neurosurgical findings in brain tumors]. In 120 cases of operated brain tumors the neurosurgical findings are compared with the results of brain scintigraphy with 99mTc-pertechnetate. The study comprises only the frequent types of brain tumors such as meningeoma, astrozytoma, glioblastoma, oligodendroglioma, neurinoma and metastases. From the neurosurgical findinds were evaluated the localisation and size of the tumor, the extent of vascularity, of cysts and necroses. These data were related to the type or radioangiography and the degree of uptake in the scintigraphy. The tumors could be demonstrated by scintigraphy in 105 of the cases. Radioangiography was obviously superior to late scintigraphy in the diagnosis of the type of tumor. The size of the tumor appeared in the meningeomas greater and in the other types of tumor smaller than found by operation. The uptake in scintigraphy showed a correlation to vascularity. Otherwise there was found no correlation between vascularity and type of radioangiography in glioblastomas. This surprising result needs further investigatiion. Half of the cases with cysts and necroses showed an inhomogeneity in the uptake by the tumor."}
{"id": "PMID:197502", "title": "Evaluation of a VNA mental health project.", "content": "Using a quasi-experimental design, discharged psychiatric patients referred to the Visiting Nurse Association of Cleveland during a nine-month period were randomly assigned to treatment or control groups. Patients were interviewed twice--after hospital discharge and six months later. Of the 110 patients who completed both interviews, which included a socially expected activities form, 62 were female, 63 nonwhite, 108 from the lowest two levels of socioeconomic status, and 74 schizophrenic. Six months postdischarge a 14% increase in employment was noted in the treatment group, who received nursing services, but no change was noted in the control group. Control group members (57%) were more likely to miss taking their prescribed medicines than were treatment group members (36%). Readmission occurred more frequently in the control (34%) than in the treatment group (28%). No difference was noted between the two groups on socially expected activities scores, possibly because: 1) the categories of the instrument may be too broad to discriminate between groups that are similar in their adjustment, 2) six months may not be a long enough time interval, 3) many patients had characteristics identified as \"unfavorable\" in reported studies, 4) an average of 2.3 visits a month by the nurses may not be adequate for the patients referred to this agency.", "contents": "Evaluation of a VNA mental health project. Using a quasi-experimental design, discharged psychiatric patients referred to the Visiting Nurse Association of Cleveland during a nine-month period were randomly assigned to treatment or control groups. Patients were interviewed twice--after hospital discharge and six months later. Of the 110 patients who completed both interviews, which included a socially expected activities form, 62 were female, 63 nonwhite, 108 from the lowest two levels of socioeconomic status, and 74 schizophrenic. Six months postdischarge a 14% increase in employment was noted in the treatment group, who received nursing services, but no change was noted in the control group. Control group members (57%) were more likely to miss taking their prescribed medicines than were treatment group members (36%). Readmission occurred more frequently in the control (34%) than in the treatment group (28%). No difference was noted between the two groups on socially expected activities scores, possibly because: 1) the categories of the instrument may be too broad to discriminate between groups that are similar in their adjustment, 2) six months may not be a long enough time interval, 3) many patients had characteristics identified as \"unfavorable\" in reported studies, 4) an average of 2.3 visits a month by the nurses may not be adequate for the patients referred to this agency."}
{"id": "PMID:197509", "title": "Estrogens for the menopause. Maximizing benefits, minimizing risks.", "content": "There is a definite place for estrogen replacement in symptomatic menopausal women. Requisites of such therapy are a through history to establish a real need, a complete gynecologic examination with a Pap smear before therapy begins and annually afterward, use of the smallest daily dose of estrogen that gives the desired effect, and periodic attempts to reduce the dosage or stop the hormone. Endometrial biopsy should be done regularly if this is feasible, and any uterine bleeding should be investigated. If the suggestions outlined are followed, maximal benefit can be achieved with minimal risk to the patient.", "contents": "Estrogens for the menopause. Maximizing benefits, minimizing risks. There is a definite place for estrogen replacement in symptomatic menopausal women. Requisites of such therapy are a through history to establish a real need, a complete gynecologic examination with a Pap smear before therapy begins and annually afterward, use of the smallest daily dose of estrogen that gives the desired effect, and periodic attempts to reduce the dosage or stop the hormone. Endometrial biopsy should be done regularly if this is feasible, and any uterine bleeding should be investigated. If the suggestions outlined are followed, maximal benefit can be achieved with minimal risk to the patient."}
{"id": "PMID:197515", "title": "Excited state lifetimes in cytochromes measured from Raman scattering data: evidence for iron-porphyrin interactions.", "content": "Resonance Raman scattering excitation profile data have been obtained on ferrocytochromes c and b5 in the alpha absorption band region. We observe in cytochrome c that the shape of the excitation profile agrees with the absorption band shape, while in cytochrome b5 it does not. In addition, we observe in cytochrome b5 a linewidth substantially larger than that in cytochrome c. From our data we conclude that the excited state lifetime in cytochrome c is longer than that in cytochrome b5 and that in cytochrome b5 the relaxation of the pi-pi* excited state configuration of the porphyrin ring is different in the x direction than in the y direction. Possible origins of these effects due to coupling to the d-d transitions of the iron atom are discussed.", "contents": "Excited state lifetimes in cytochromes measured from Raman scattering data: evidence for iron-porphyrin interactions. Resonance Raman scattering excitation profile data have been obtained on ferrocytochromes c and b5 in the alpha absorption band region. We observe in cytochrome c that the shape of the excitation profile agrees with the absorption band shape, while in cytochrome b5 it does not. In addition, we observe in cytochrome b5 a linewidth substantially larger than that in cytochrome c. From our data we conclude that the excited state lifetime in cytochrome c is longer than that in cytochrome b5 and that in cytochrome b5 the relaxation of the pi-pi* excited state configuration of the porphyrin ring is different in the x direction than in the y direction. Possible origins of these effects due to coupling to the d-d transitions of the iron atom are discussed."}
{"id": "PMID:197516", "title": "Structural adaptations of lactate dehydrogenase isozymes.", "content": "The three-dimensional structures of dogfish M4 (muscle) and pig H4 (heart) lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) have been determined and correlated with the amino acid sequences of the dogfish M4, pig M4, pig H4, chicken M4, and chicken H4 lactate dehydrogenase isozymes. These results have been related to the known differences of physicochemical properties between the M and H lactate dehydrogenase isozymes. By far the largest structural alterations occur in the transition between the \"apo\" and \"ternary complex\" conformational states of the enzyme rather than between species or isozymes. The major catalytic difference can be explained by a replacement of alanine (in the M chain) with a glutamine (in the H chain) in the vicinity of the binding site of the coenzyme phosphates. The known immunological differentiation of the M and H isozymes is consistent with the differences in their amino acid sequences.", "contents": "Structural adaptations of lactate dehydrogenase isozymes. The three-dimensional structures of dogfish M4 (muscle) and pig H4 (heart) lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) have been determined and correlated with the amino acid sequences of the dogfish M4, pig M4, pig H4, chicken M4, and chicken H4 lactate dehydrogenase isozymes. These results have been related to the known differences of physicochemical properties between the M and H lactate dehydrogenase isozymes. By far the largest structural alterations occur in the transition between the \"apo\" and \"ternary complex\" conformational states of the enzyme rather than between species or isozymes. The major catalytic difference can be explained by a replacement of alanine (in the M chain) with a glutamine (in the H chain) in the vicinity of the binding site of the coenzyme phosphates. The known immunological differentiation of the M and H isozymes is consistent with the differences in their amino acid sequences."}
{"id": "PMID:197517", "title": "Polypeptides of cells transformed by RNA or DNA tumor viruses.", "content": "Proteins solubilized from normal BALB/3T3 cells and BALB/3T3 transformed by simian virus 40 or Kirsten sarcoma virus have been analyzed by two-dimensional gel electrophoresis and tryptic peptide mapping. A large fraction of the polypeptides of the virus-transformed cells, about 30%, were different from normal cells. In contrast to the marked differences between normal and transformed cells, the polypeptides of the DNA and RNA virus-transformed cells were almost identical. These findings were observed with polypeptides stained by Coomassie Blue, or labeled with [14C]glucosamine or [35S]methionine. Pulse-chase analysis showed that most of the polypeptides were stable during 20 hr of incubation. The identity of several polypeptides was confirmed by tryptic peptide mapping.", "contents": "Polypeptides of cells transformed by RNA or DNA tumor viruses. Proteins solubilized from normal BALB/3T3 cells and BALB/3T3 transformed by simian virus 40 or Kirsten sarcoma virus have been analyzed by two-dimensional gel electrophoresis and tryptic peptide mapping. A large fraction of the polypeptides of the virus-transformed cells, about 30%, were different from normal cells. In contrast to the marked differences between normal and transformed cells, the polypeptides of the DNA and RNA virus-transformed cells were almost identical. These findings were observed with polypeptides stained by Coomassie Blue, or labeled with [14C]glucosamine or [35S]methionine. Pulse-chase analysis showed that most of the polypeptides were stable during 20 hr of incubation. The identity of several polypeptides was confirmed by tryptic peptide mapping."}
{"id": "PMID:197518", "title": "Importance of 5'-terminal blocking structure to stabilize mRNA in eukaryotic protein synthesis.", "content": "The 7-methylguanylic acid residue confronting the 5'-terminal nucleotide of mRNA through two pyrophosphate linkages was completely removed by tobacco pyrophosphatase from mRNAs of cytoplasmic polyhedrosis virus, tobacco mosaic virus (viral RNA), and globin without any scission in the inner part of the RNA chain. Protein synthesis ability in a wheat germ cell-free system was lost after this treatment of all three kinds of mRNA. The initiation complexes for protein synthesis of these three RNAs were not obtained after using tobacco phosphodiesterase-treated mRNA. On incubation of mRNA in a wheat germ extract, the mRNA lacking m7G was quickly degraded from the 5' terminus in an exonucleolytic way, whereas the intact mRNA remained stable. These results show that one of the confronting nucleotide structure's functions is to stabilize the mRNA, to prevent its degradation.", "contents": "Importance of 5'-terminal blocking structure to stabilize mRNA in eukaryotic protein synthesis. The 7-methylguanylic acid residue confronting the 5'-terminal nucleotide of mRNA through two pyrophosphate linkages was completely removed by tobacco pyrophosphatase from mRNAs of cytoplasmic polyhedrosis virus, tobacco mosaic virus (viral RNA), and globin without any scission in the inner part of the RNA chain. Protein synthesis ability in a wheat germ cell-free system was lost after this treatment of all three kinds of mRNA. The initiation complexes for protein synthesis of these three RNAs were not obtained after using tobacco phosphodiesterase-treated mRNA. On incubation of mRNA in a wheat germ extract, the mRNA lacking m7G was quickly degraded from the 5' terminus in an exonucleolytic way, whereas the intact mRNA remained stable. These results show that one of the confronting nucleotide structure's functions is to stabilize the mRNA, to prevent its degradation."}
{"id": "PMID:197519", "title": "Binding of Zn2+ to rat liver fructose-1,6-bisphosphatase and its effect on the catalytic properties.", "content": "Rat liver fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) contains 12 binding sites for Zn2+ per molecule, or 3 per subunit, as determined by gel filtration and by precipitation of an insoluble Zn2+-enzyme complex. The first set of sites binds Zn2+ with very high affinity, and the binding constant for these sites could not be determined. The average values of the dissociation constants for the second and third sets of sites were approximately 0.4 and 1.5 muM, respectively. The third set of sites, having lowest affinity, appears to be identical to the binding sites for the activating cation, Mg2+, and the binding of Zn2+ to this set of sites is prevented by the addition of Mg2+. Binding of the first 4 equivalents of Zn2+ yields an enzyme of intermediate activity, while the binding of 8 equivalent results in almost complete inhibition of catalytic activity. Thus Zn2+ appears to function as both an activator and a negative allosteric regulator of fructose-1,6-bisphosphatase activity.", "contents": "Binding of Zn2+ to rat liver fructose-1,6-bisphosphatase and its effect on the catalytic properties. Rat liver fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) contains 12 binding sites for Zn2+ per molecule, or 3 per subunit, as determined by gel filtration and by precipitation of an insoluble Zn2+-enzyme complex. The first set of sites binds Zn2+ with very high affinity, and the binding constant for these sites could not be determined. The average values of the dissociation constants for the second and third sets of sites were approximately 0.4 and 1.5 muM, respectively. The third set of sites, having lowest affinity, appears to be identical to the binding sites for the activating cation, Mg2+, and the binding of Zn2+ to this set of sites is prevented by the addition of Mg2+. Binding of the first 4 equivalents of Zn2+ yields an enzyme of intermediate activity, while the binding of 8 equivalent results in almost complete inhibition of catalytic activity. Thus Zn2+ appears to function as both an activator and a negative allosteric regulator of fructose-1,6-bisphosphatase activity."}
{"id": "PMID:197520", "title": "Crosslinked histone octamer as a model of the nucleosome core.", "content": "When histones in chromatin core particles were crosslinked with dimethylsuberimidate, the resulting particles had properties closely similar to those of native core particles. A crosslinked octameric histone complex was isolated from these particles under nondenaturing conditions. Upon reaction with DNA, this octameric protein folded the DNA into a structure closely resembling that of native core particles as verified by various techniques; protein denaturants were necessary for reassociation. The histone octamer is useful as a model of the nucleosome protein core and for studying histone-DNA interactions that occur in nucleosomes.", "contents": "Crosslinked histone octamer as a model of the nucleosome core. When histones in chromatin core particles were crosslinked with dimethylsuberimidate, the resulting particles had properties closely similar to those of native core particles. A crosslinked octameric histone complex was isolated from these particles under nondenaturing conditions. Upon reaction with DNA, this octameric protein folded the DNA into a structure closely resembling that of native core particles as verified by various techniques; protein denaturants were necessary for reassociation. The histone octamer is useful as a model of the nucleosome protein core and for studying histone-DNA interactions that occur in nucleosomes."}
{"id": "PMID:197521", "title": "Histones: metabolism in simian virus 40-infected cells and incorporation into virions.", "content": "The infection of confluent monkey cells with simian virus 40 induced the synthesis of both cellular DNA and histones. However, during the course of infection, cellular histone synthesis was uncoupled from cellular DNA replication and became coupled to viral DNA replication. The synthesis of all five host histone species was induced after virus infection and they appeared to be more highly phosphorylated than their couterparts in uninfected cells. At late times after infection, the cells contained twice as much histones as did uninfected cells. All the histone species except H1 were incorporated into virions. Compared to cellular histones, virion histones were enriched in the arginine-rich species H3 and H4. Although both old and newly synthesized cellular histones were incorporated into virions, there were about 5 times more newly synthesized than old histone polypeptides in virions.", "contents": "Histones: metabolism in simian virus 40-infected cells and incorporation into virions. The infection of confluent monkey cells with simian virus 40 induced the synthesis of both cellular DNA and histones. However, during the course of infection, cellular histone synthesis was uncoupled from cellular DNA replication and became coupled to viral DNA replication. The synthesis of all five host histone species was induced after virus infection and they appeared to be more highly phosphorylated than their couterparts in uninfected cells. At late times after infection, the cells contained twice as much histones as did uninfected cells. All the histone species except H1 were incorporated into virions. Compared to cellular histones, virion histones were enriched in the arginine-rich species H3 and H4. Although both old and newly synthesized cellular histones were incorporated into virions, there were about 5 times more newly synthesized than old histone polypeptides in virions."}
{"id": "PMID:197522", "title": "Topographic separation of adenylate cyclase and hormone receptors in the plasma membrane of toad erythrocyte ghosts.", "content": "Brief sonication of whole erythrocyte plasma membranes (ghosts) from toads at 4 degrees does not inactivate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] or destroy the receptor binding properties of hydroxybenzylpindolol or insulin. The hormonal (but not the fluoride-induced) stimulation of this enzyme is, however, lost. Fractionation of the small, resealed membrane fragments (vesicles) on discontinuous sucrose gradients results in the separation of vesicle populations differing grossly in size and protein composition. In addition, the distribution of the beta-adrenergic receptor, an insulin binding site, and adenylate cyclase among these vesicles fractions differs. The pattern of distribution of these functional structures can be altered differentially by manipulations of the ghosts before sonication. For example, brief preincubation with isoproterenol leads to a change in the relative distribution of beta-receptor (but not adenylate cyclase) among the various vesicle fractions; this effect is not obtained with beta-receptor antagonists, which block the isoproterenol effect. Exposure of the ghosts to different temperatures, changes in the divalent cation composition of the medium, or the addition of ATP also leads to changes in the distribution of surface markers of the subsequently formed vesicles. The results indicate gross asymmetries in the distribution of protein components within the plane of the membrane and raise important questions regarding the manner whereby functionally related and coupled components, such as hormone receptors and adenylate cyclase, interact.", "contents": "Topographic separation of adenylate cyclase and hormone receptors in the plasma membrane of toad erythrocyte ghosts. Brief sonication of whole erythrocyte plasma membranes (ghosts) from toads at 4 degrees does not inactivate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] or destroy the receptor binding properties of hydroxybenzylpindolol or insulin. The hormonal (but not the fluoride-induced) stimulation of this enzyme is, however, lost. Fractionation of the small, resealed membrane fragments (vesicles) on discontinuous sucrose gradients results in the separation of vesicle populations differing grossly in size and protein composition. In addition, the distribution of the beta-adrenergic receptor, an insulin binding site, and adenylate cyclase among these vesicles fractions differs. The pattern of distribution of these functional structures can be altered differentially by manipulations of the ghosts before sonication. For example, brief preincubation with isoproterenol leads to a change in the relative distribution of beta-receptor (but not adenylate cyclase) among the various vesicle fractions; this effect is not obtained with beta-receptor antagonists, which block the isoproterenol effect. Exposure of the ghosts to different temperatures, changes in the divalent cation composition of the medium, or the addition of ATP also leads to changes in the distribution of surface markers of the subsequently formed vesicles. The results indicate gross asymmetries in the distribution of protein components within the plane of the membrane and raise important questions regarding the manner whereby functionally related and coupled components, such as hormone receptors and adenylate cyclase, interact."}
{"id": "PMID:197523", "title": "Glucocorticoid-stimulated accumulation of mouse mammary tumor virus RNA: increased rate of synthesis of viral RNA.", "content": "Glucocorticoid hormones specifically increase the intracellular concentration of mouse mammary tumor virus (MMTV) RNA in a cultured cell line from a GR mouse mammary carcinoma (GR) and in an MMTV-infected rat hepatoma cell line (M1.19). In contrast, these steroids have no effect on the concentration of MMTV RNA in a lymphoma line, S49, from a Balb/c mouse. Using a molecular hybridization procedure to detect newly synthesized RNA, we have directly measured the effect of dexamethasone, a synthetic glucocorticoid, on the rate of MMTV RNA synthesis. In GR cells the hormone causes a 10-fold increase in the rate of synthesis of viral RNA without appreciably affecting the overall rate of cellular RNA synthesis. The transition from the basal to the maximally stimulated rate of MMTV RNA synthesis occurs within the earliest labeling period, 0-15 min after addition of the hormone. Thus, it appears that glucocorticoids regulate MMTV genes principally by this rapid and specific alteration of their rate of transcription. Similar results are obtained in M1.19 rat hepatoma cells. In contrast, dexamethasone does not affect the rate of viral RNA synthesis in S49 lymphoma cells.", "contents": "Glucocorticoid-stimulated accumulation of mouse mammary tumor virus RNA: increased rate of synthesis of viral RNA. Glucocorticoid hormones specifically increase the intracellular concentration of mouse mammary tumor virus (MMTV) RNA in a cultured cell line from a GR mouse mammary carcinoma (GR) and in an MMTV-infected rat hepatoma cell line (M1.19). In contrast, these steroids have no effect on the concentration of MMTV RNA in a lymphoma line, S49, from a Balb/c mouse. Using a molecular hybridization procedure to detect newly synthesized RNA, we have directly measured the effect of dexamethasone, a synthetic glucocorticoid, on the rate of MMTV RNA synthesis. In GR cells the hormone causes a 10-fold increase in the rate of synthesis of viral RNA without appreciably affecting the overall rate of cellular RNA synthesis. The transition from the basal to the maximally stimulated rate of MMTV RNA synthesis occurs within the earliest labeling period, 0-15 min after addition of the hormone. Thus, it appears that glucocorticoids regulate MMTV genes principally by this rapid and specific alteration of their rate of transcription. Similar results are obtained in M1.19 rat hepatoma cells. In contrast, dexamethasone does not affect the rate of viral RNA synthesis in S49 lymphoma cells."}
{"id": "PMID:197524", "title": "Control of growth by picolinic acid: differential response of normal and transformed cells.", "content": "Picolinic acid reversibly inhibits the growth of cultured cells. Fourteen other pyridine derivatives were ineffective or toxic. Untransformed normal rat kidney (NRK) cells are reversibly arrested in the G(1) stage of the growth cycle as shown by cell counts, mitotic index, [(3)H]thymidine incorporation, and flow microfluorometry. Flow microfluorometry was used to monitor the effects of picolinic acid on numerous other cell lines. Normal cells are blocked in G(1), whereas transformed cells show responses that are dependent upon the transforming virus and independent of species or origin of the cell line. Kirsten sarcoma virus-transformed cells are blocked in G(1). Simian virus 40-transformed cells progress to a G(2) block. Cells transformed by polyoma or Harvey sarcoma virus with Moloney virus coat have flow microfluorometry profiles that indicate blocks in both G(1) and G(2). Cells transformed with Moloney sarcoma virus are not blocked in a specific phase of the cell cycle. Picolinic acid does not change the levels of NAD(+) plus NADH; however, the growth inhibition by picolinic acid is partially overcome by nicotinamide. These results suggest that picolinic acid interacts with a specific growth control mechanism that may involve NAD(+) and that this control mechanism is altered by different transforming viruses in different manners.", "contents": "Control of growth by picolinic acid: differential response of normal and transformed cells. Picolinic acid reversibly inhibits the growth of cultured cells. Fourteen other pyridine derivatives were ineffective or toxic. Untransformed normal rat kidney (NRK) cells are reversibly arrested in the G(1) stage of the growth cycle as shown by cell counts, mitotic index, [(3)H]thymidine incorporation, and flow microfluorometry. Flow microfluorometry was used to monitor the effects of picolinic acid on numerous other cell lines. Normal cells are blocked in G(1), whereas transformed cells show responses that are dependent upon the transforming virus and independent of species or origin of the cell line. Kirsten sarcoma virus-transformed cells are blocked in G(1). Simian virus 40-transformed cells progress to a G(2) block. Cells transformed by polyoma or Harvey sarcoma virus with Moloney virus coat have flow microfluorometry profiles that indicate blocks in both G(1) and G(2). Cells transformed with Moloney sarcoma virus are not blocked in a specific phase of the cell cycle. Picolinic acid does not change the levels of NAD(+) plus NADH; however, the growth inhibition by picolinic acid is partially overcome by nicotinamide. These results suggest that picolinic acid interacts with a specific growth control mechanism that may involve NAD(+) and that this control mechanism is altered by different transforming viruses in different manners."}
{"id": "PMID:197525", "title": "Specific changes in the collagen phenotype of BALB 3T3 cells as a result of transformation by sarcoma viruses or a chemical carcinogen.", "content": "Radioactive proline-labeled procollagen, accumulated during a 3-hr incubation of normal and transformed BALB 3T3 cultures, was treated with pepsin and the resulting collagen components were analyzed by carboxymethyl-cellulose chromatography and sodium dodecyl sulfate/polyacrylamide gel electrophoresis in the presence or absence of reducing agent. Collagen in the medium of three subclones of BALB 3T3 A-31 that exhibited contact-inhibition of growth at confluence, as well as in the medium of one that did not, consisted of alpha(1) and alpha(2) subunits in the ratio of 3:1, suggesting that 3T3 cells synthesize type I collagen, [alpha(1)(I)](2)alpha(2), and another type, which we have designated X, composed of alpha(1) chains, which may or may not be identical to alpha(1)(I). Culture medium from 3T3 transformed by Kirsten or Moloney sarcoma virus contained type I collagen and another type differing from I and X and designated as type Y. The latter appeared to be similar to type III collagen [alpha(1)(III)](3), since it contained intrahelical disulfide bonds. Analysis of intracellular collagen also demonstrated the presence of type III in Ki-3T3 and its absence from 3T3 cells. Collagen components from the medium of a simian virus 40 transformant were identical to those of the contact-inhibited clones, while the collagen from a 4-nitroquinoline-1-oxide-induced transformant was composed mainly of two components differing from alpha(1)(I), alpha(2), or alpha(1)(III). These results suggest that the type of collagen accumulated in transformed cell cultures may be specifically related to the transforming agent.", "contents": "Specific changes in the collagen phenotype of BALB 3T3 cells as a result of transformation by sarcoma viruses or a chemical carcinogen. Radioactive proline-labeled procollagen, accumulated during a 3-hr incubation of normal and transformed BALB 3T3 cultures, was treated with pepsin and the resulting collagen components were analyzed by carboxymethyl-cellulose chromatography and sodium dodecyl sulfate/polyacrylamide gel electrophoresis in the presence or absence of reducing agent. Collagen in the medium of three subclones of BALB 3T3 A-31 that exhibited contact-inhibition of growth at confluence, as well as in the medium of one that did not, consisted of alpha(1) and alpha(2) subunits in the ratio of 3:1, suggesting that 3T3 cells synthesize type I collagen, [alpha(1)(I)](2)alpha(2), and another type, which we have designated X, composed of alpha(1) chains, which may or may not be identical to alpha(1)(I). Culture medium from 3T3 transformed by Kirsten or Moloney sarcoma virus contained type I collagen and another type differing from I and X and designated as type Y. The latter appeared to be similar to type III collagen [alpha(1)(III)](3), since it contained intrahelical disulfide bonds. Analysis of intracellular collagen also demonstrated the presence of type III in Ki-3T3 and its absence from 3T3 cells. Collagen components from the medium of a simian virus 40 transformant were identical to those of the contact-inhibited clones, while the collagen from a 4-nitroquinoline-1-oxide-induced transformant was composed mainly of two components differing from alpha(1)(I), alpha(2), or alpha(1)(III). These results suggest that the type of collagen accumulated in transformed cell cultures may be specifically related to the transforming agent."}
{"id": "PMID:197526", "title": "Segregation of genetic information for a B-tropic leukemia virus with the structural locus for BALB:virus-1.", "content": "A B-tropic type-C RNA virus isolatable from lymphoreticular tumors of the inbred BALB/c mouse strain has previously been shown to be leukemogenic in its natural host. This virus is not chemically inducible from BALB/c embryo cells or from embryo lines containing segregating inducibility loci for two known endogenous type-C viruses of BALB/c cells. Molecular hybridization and type-specific immunologic assays demonstrate a high degree of genetic homology between the B-tropic leukemia virus and BALB:virus-1, an N-tropic endogenous virus of BALB/c cells. Genetic sequences specific for BALB:virus-1 are shown to segregate with the locus for BALB:virus-1 induction in genetic crosses between BALB/c and the noninducible NIH Swiss strain. Thus, if the information of the B-tropic virus is encoded in the genome of the animal, it must be closely linked to the structural locus for BALB:virus-1. The evidence is consistent with a mechanism by which a small genetic alteration in BALB:virus-1 leads to a virus, whose growth is unrestricted, and subsequently to the development of neoplasia.", "contents": "Segregation of genetic information for a B-tropic leukemia virus with the structural locus for BALB:virus-1. A B-tropic type-C RNA virus isolatable from lymphoreticular tumors of the inbred BALB/c mouse strain has previously been shown to be leukemogenic in its natural host. This virus is not chemically inducible from BALB/c embryo cells or from embryo lines containing segregating inducibility loci for two known endogenous type-C viruses of BALB/c cells. Molecular hybridization and type-specific immunologic assays demonstrate a high degree of genetic homology between the B-tropic leukemia virus and BALB:virus-1, an N-tropic endogenous virus of BALB/c cells. Genetic sequences specific for BALB:virus-1 are shown to segregate with the locus for BALB:virus-1 induction in genetic crosses between BALB/c and the noninducible NIH Swiss strain. Thus, if the information of the B-tropic virus is encoded in the genome of the animal, it must be closely linked to the structural locus for BALB:virus-1. The evidence is consistent with a mechanism by which a small genetic alteration in BALB:virus-1 leads to a virus, whose growth is unrestricted, and subsequently to the development of neoplasia."}
{"id": "PMID:197527", "title": "Specific action of T4 endonuclease V on damaged DNA in xeroderma pigmentosum cells in vivo.", "content": "The specific action of T4 endonuclease V on damaged DNA in xeroderma pigmentosum cells was examined using an in vivo assay system with hemagglutinating virus of Japan (Sendai virus) inactivated by UV light. A clear dose response was observed between the level of UV-induce unscheduled DNA synthesis of xeroderma pigmentosum cells and the amount of T4 endonuclease V activity added. The T4 enzyme was unstable in human cells, and its half-life was 3 hr. Fractions derived from an extract of Escherichia coli infected with T4V1, a mutant defective in the endonuclease V gene, showed no ability to restore the UV-induced unscheduled DNA synthesis of xeroderma pigmentosum cells. However, fractions derived from an extract of T4D-infected E. coli with endonuclease V activity were effective. The T4 enzyme was effective in xeroderma pigmentosum cells on DNA damaged by UV light but not in cells damaged by 4-nitroquinoline 1-oxide. The results of these experiments show that the T4 enzyme has a specific action on human cell DNA in vivo. Treatment with the T4 enzyme increased the survival of group A xeroderma pigmentosum cells after UV irradiation.", "contents": "Specific action of T4 endonuclease V on damaged DNA in xeroderma pigmentosum cells in vivo. The specific action of T4 endonuclease V on damaged DNA in xeroderma pigmentosum cells was examined using an in vivo assay system with hemagglutinating virus of Japan (Sendai virus) inactivated by UV light. A clear dose response was observed between the level of UV-induce unscheduled DNA synthesis of xeroderma pigmentosum cells and the amount of T4 endonuclease V activity added. The T4 enzyme was unstable in human cells, and its half-life was 3 hr. Fractions derived from an extract of Escherichia coli infected with T4V1, a mutant defective in the endonuclease V gene, showed no ability to restore the UV-induced unscheduled DNA synthesis of xeroderma pigmentosum cells. However, fractions derived from an extract of T4D-infected E. coli with endonuclease V activity were effective. The T4 enzyme was effective in xeroderma pigmentosum cells on DNA damaged by UV light but not in cells damaged by 4-nitroquinoline 1-oxide. The results of these experiments show that the T4 enzyme has a specific action on human cell DNA in vivo. Treatment with the T4 enzyme increased the survival of group A xeroderma pigmentosum cells after UV irradiation."}
{"id": "PMID:197528", "title": "Suppressor cell regulation of immune response to tumors: abrogation by adult thymectomy.", "content": "The regulatory role of the adult thymus on the appearance of cytotoxic and suppressor T cells (thymus-derived lymphocytes) to allogeneic and autochthonous virus-induced tumors in mice was investigated. It was demonstrated that C57BL/6 mice challenged with allogeneic P815 mastocytoma cells and complete Freund's adjuvant failed to develop cytotoxic cells but instead developed suppressor T cells which inhibited cytotoxic T cell function. Further, adjuvant-induced suppressor cells prevented the primary in vitro induction of cytotoxic T cells to P815 mastocytoma cells. In contrast, adult thymectomized animals, when challenged with adjuvant and allogeneic cells, had a normal cytotoxic response in vivo and their cells could not inhibit the generation of cytotoxic T cells in vitro. These studies suggested that the intact adult thymus was necessary for the induction of suppressor cells. Moreover, suppressor cells regulated cytotoxic T cell activity both in vivo and in vitro. Further, it was shown that adjuvant could prevent the normal immune response to virus-induced tumors. BALB/c mice treated with murine sarcoma virus developed tumors which reached a maximal size by day 14 and then regressed. Sham thymectomized animals treated with virus and complete Freund's adjuvant to generate suppressor cells died from progressive tumor growth. In contrast, thymectomized animals similarly treated had normal regression of tumor and survived. These studies lead to the conclusion that the adult thymus may regulate immune responsiveness by the export of suppressor T cells which regulate other T cell responses to both allogeneic and tumor antigens.", "contents": "Suppressor cell regulation of immune response to tumors: abrogation by adult thymectomy. The regulatory role of the adult thymus on the appearance of cytotoxic and suppressor T cells (thymus-derived lymphocytes) to allogeneic and autochthonous virus-induced tumors in mice was investigated. It was demonstrated that C57BL/6 mice challenged with allogeneic P815 mastocytoma cells and complete Freund's adjuvant failed to develop cytotoxic cells but instead developed suppressor T cells which inhibited cytotoxic T cell function. Further, adjuvant-induced suppressor cells prevented the primary in vitro induction of cytotoxic T cells to P815 mastocytoma cells. In contrast, adult thymectomized animals, when challenged with adjuvant and allogeneic cells, had a normal cytotoxic response in vivo and their cells could not inhibit the generation of cytotoxic T cells in vitro. These studies suggested that the intact adult thymus was necessary for the induction of suppressor cells. Moreover, suppressor cells regulated cytotoxic T cell activity both in vivo and in vitro. Further, it was shown that adjuvant could prevent the normal immune response to virus-induced tumors. BALB/c mice treated with murine sarcoma virus developed tumors which reached a maximal size by day 14 and then regressed. Sham thymectomized animals treated with virus and complete Freund's adjuvant to generate suppressor cells died from progressive tumor growth. In contrast, thymectomized animals similarly treated had normal regression of tumor and survived. These studies lead to the conclusion that the adult thymus may regulate immune responsiveness by the export of suppressor T cells which regulate other T cell responses to both allogeneic and tumor antigens."}
{"id": "PMID:197529", "title": "Common precursor to corticotropins and endorphins.", "content": "Double-antibody immunoprecipitation procedures with antisera to endorphins and to corticotropin (ACTH) were used to study the biosynthesis of these peptides in a mouse pituitary tumor cell line. Cultures were incubated with a (3)H-labeled amino acid, and aliquots of culture medium were immunoprecipitated. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of [(3)H]phenylalanine-labeled immunoprecipitates prepared with endorphin antisera resolved three forms of endorphin with apparent molecular weights of 31,000, 11,700, and 3500; immunoprecipitates prepared with the ACTH antiserum contained four forms of ACTH with apparent molecular weights of 31,000, 23,000, 13,000 and <4500. Sequential immunoprecipitation of culture medium with the ACTH antiserum and then with the endorphin antiserum (or the reverse order) indicated that both antisera precipitated the same 31,000 dalton molecule. Purified pools of the different forms of ACTH and endorphin were prepared by immunoprecipitation and gel filtration. The tryptic peptides found in [(3)H]phenylalanine- or [(3)H]tryptophan-labeled 31,000 dalton ACTH were identical to the tryptic peptides found in digests of 31,000 dalton endorphin labeled with the same amino acid. A tryptic peptide similar to the lipotropin tryptic peptide [betaLPH(61-69)] that contains the opiate-active methionine-enkephalin sequence could be identified in 31,000 dalton ACTH and in all the different forms of endorphin. Most of the peptide cleaved from 31,000 dalton ACTH when it is converted to 23,000 dalton ACTH could be precipitated by endorphin antisera; this 11,700 dalton endorphin molecule is similar to the pituitary hormone betaLPH in size and structure. The 3500 dalton endorphin is similar to beta-endorphin in size and structure. The culture medium from the AtT-20 mouse pituitary tumor cells contained approximately equimolar amounts of ACTH-related peptides and endorphin-related peptides.", "contents": "Common precursor to corticotropins and endorphins. Double-antibody immunoprecipitation procedures with antisera to endorphins and to corticotropin (ACTH) were used to study the biosynthesis of these peptides in a mouse pituitary tumor cell line. Cultures were incubated with a (3)H-labeled amino acid, and aliquots of culture medium were immunoprecipitated. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of [(3)H]phenylalanine-labeled immunoprecipitates prepared with endorphin antisera resolved three forms of endorphin with apparent molecular weights of 31,000, 11,700, and 3500; immunoprecipitates prepared with the ACTH antiserum contained four forms of ACTH with apparent molecular weights of 31,000, 23,000, 13,000 and <4500. Sequential immunoprecipitation of culture medium with the ACTH antiserum and then with the endorphin antiserum (or the reverse order) indicated that both antisera precipitated the same 31,000 dalton molecule. Purified pools of the different forms of ACTH and endorphin were prepared by immunoprecipitation and gel filtration. The tryptic peptides found in [(3)H]phenylalanine- or [(3)H]tryptophan-labeled 31,000 dalton ACTH were identical to the tryptic peptides found in digests of 31,000 dalton endorphin labeled with the same amino acid. A tryptic peptide similar to the lipotropin tryptic peptide [betaLPH(61-69)] that contains the opiate-active methionine-enkephalin sequence could be identified in 31,000 dalton ACTH and in all the different forms of endorphin. Most of the peptide cleaved from 31,000 dalton ACTH when it is converted to 23,000 dalton ACTH could be precipitated by endorphin antisera; this 11,700 dalton endorphin molecule is similar to the pituitary hormone betaLPH in size and structure. The 3500 dalton endorphin is similar to beta-endorphin in size and structure. The culture medium from the AtT-20 mouse pituitary tumor cells contained approximately equimolar amounts of ACTH-related peptides and endorphin-related peptides."}
{"id": "PMID:197530", "title": "Isolation and characterization of the opioid peptides from rat pituitary: beta-lipotropin.", "content": "Rat beta-lipotropin was isolated from 40 anterior pituitaries using high efficiency chromatography columns and sensitive fluorometric methods. The beta-lipotropin was characterized as to molecular weight, amino acid composition, and generation of opioid activity by trypsinization. Other opioid peptides, as well as a precursor to opioid peptides with a molecular weight larger than that of beta-lipotropin, were observed in this tissue.", "contents": "Isolation and characterization of the opioid peptides from rat pituitary: beta-lipotropin. Rat beta-lipotropin was isolated from 40 anterior pituitaries using high efficiency chromatography columns and sensitive fluorometric methods. The beta-lipotropin was characterized as to molecular weight, amino acid composition, and generation of opioid activity by trypsinization. Other opioid peptides, as well as a precursor to opioid peptides with a molecular weight larger than that of beta-lipotropin, were observed in this tissue."}
{"id": "PMID:197531", "title": "Isolation of transforming murine leukemia viruses from mice with a high incidence of spontaneous lymphoma.", "content": "Murine leukemia viruses capable of malignant transformation of mink tissue culture cells have been isolated from an AKR thymoma cell line and from a spontaneous reticulum cell sarcoma in an NIH Swiss mouse partially congenic for the AKR ecotropic virus-inducing locus Akv-2. In contrast to the recently described mink cell focus-inducing strains of murine leukemia virus, at least one of the two transforming strains is replication defective. Nonproducer mink cells carrying the genome of the transforming virus of AKR origin have been isolated, and pseudotype transforming viruses generated.", "contents": "Isolation of transforming murine leukemia viruses from mice with a high incidence of spontaneous lymphoma. Murine leukemia viruses capable of malignant transformation of mink tissue culture cells have been isolated from an AKR thymoma cell line and from a spontaneous reticulum cell sarcoma in an NIH Swiss mouse partially congenic for the AKR ecotropic virus-inducing locus Akv-2. In contrast to the recently described mink cell focus-inducing strains of murine leukemia virus, at least one of the two transforming strains is replication defective. Nonproducer mink cells carrying the genome of the transforming virus of AKR origin have been isolated, and pseudotype transforming viruses generated."}
{"id": "PMID:197556", "title": "Effect of benzodiazepines on central serotonergic neuron systems.", "content": "Intracerebral (i.c.) injection of serotonin (5-HT) into mice induced head twitches in a dose-dependent manner at 10 min after injection. The head twitches induced by 5-HT (i.c.) were potentiated by the pretreatment of isocarboxazid (3 mg/kg i.p.), and inhibited by cyproheptadine (0.3 mg/kg i.p.), a 5-HT antagonist. Benzodiazepines such as fludiazepam and diazepam potentiated the head twitches induced by 5-HT (i.c.) in a dose-dependent manner. Mescaline (50 mg/kg i.p.) also induced head twitches in mice at 15 and 30 min after injection. Benzodiazepines potentiated the head twitches induced by mescaline in a dose-dependent manner. Cyproheptadine blocked the potentiating effect of benzodiazepines on the head twitches induced by both 5-HT (i.c.) and mescaline. By repeated administration of fludiazepam or diazepam for 5 days, the potentiating effect of both drugs on the head twitches induced by mescaline was unchanged and their anticonvulsant effects were not modified. In contrast, the potency of both drugs on muscle relaxation was significantly decreased by repeated administration. Benzodiazepines failed to change the uptake of 5-HT into the synaptosomal fractions from the rat brain. These results suggest that the pharmacological action of benzodiazepines is derived at least in part from their activating effect on 5-HT receptors.", "contents": "Effect of benzodiazepines on central serotonergic neuron systems. Intracerebral (i.c.) injection of serotonin (5-HT) into mice induced head twitches in a dose-dependent manner at 10 min after injection. The head twitches induced by 5-HT (i.c.) were potentiated by the pretreatment of isocarboxazid (3 mg/kg i.p.), and inhibited by cyproheptadine (0.3 mg/kg i.p.), a 5-HT antagonist. Benzodiazepines such as fludiazepam and diazepam potentiated the head twitches induced by 5-HT (i.c.) in a dose-dependent manner. Mescaline (50 mg/kg i.p.) also induced head twitches in mice at 15 and 30 min after injection. Benzodiazepines potentiated the head twitches induced by mescaline in a dose-dependent manner. Cyproheptadine blocked the potentiating effect of benzodiazepines on the head twitches induced by both 5-HT (i.c.) and mescaline. By repeated administration of fludiazepam or diazepam for 5 days, the potentiating effect of both drugs on the head twitches induced by mescaline was unchanged and their anticonvulsant effects were not modified. In contrast, the potency of both drugs on muscle relaxation was significantly decreased by repeated administration. Benzodiazepines failed to change the uptake of 5-HT into the synaptosomal fractions from the rat brain. These results suggest that the pharmacological action of benzodiazepines is derived at least in part from their activating effect on 5-HT receptors."}
{"id": "PMID:197557", "title": "Further studies of the aggressive behavior induced by delta9-tetrahydrocannabinol in REM sleep-deprived rats.", "content": "The aggressive behavior induced by delta9-tetrahydrocannabinol in pairs of REM sleep-deprived rats was studied in five experiments by measuring dominant and submissive behavioral patterns. When 2 REM-deprived rats received delta9-THC, one of the animals displayed very aggressive postures, while its partner assumed incomplete defensive postures. The intensity of these behavioral postures was dose-dependent. In pairs composed of one REM-deprived rat injected with delta9-THC and one normal or one REM-deprived partner injected with control solution the deprived/drugged rat showed an aggressive posture and catatonia, or a strikingly bizarre behavior, while the control partner displayed typical defensive postures. The behavioral alterations induced in REM-deprived rats by amphetamine, LSD-25, and pentobarbital failed to provoke defense postures in the normal rats paired with them; however, apomorphine partially mimicked the delta9-THC-effects. It is concluded that in REM-deprived rats delta9-THC not only provokes aggressive behavior but also impairs the defensive-submissive behavioral patterns.", "contents": "Further studies of the aggressive behavior induced by delta9-tetrahydrocannabinol in REM sleep-deprived rats. The aggressive behavior induced by delta9-tetrahydrocannabinol in pairs of REM sleep-deprived rats was studied in five experiments by measuring dominant and submissive behavioral patterns. When 2 REM-deprived rats received delta9-THC, one of the animals displayed very aggressive postures, while its partner assumed incomplete defensive postures. The intensity of these behavioral postures was dose-dependent. In pairs composed of one REM-deprived rat injected with delta9-THC and one normal or one REM-deprived partner injected with control solution the deprived/drugged rat showed an aggressive posture and catatonia, or a strikingly bizarre behavior, while the control partner displayed typical defensive postures. The behavioral alterations induced in REM-deprived rats by amphetamine, LSD-25, and pentobarbital failed to provoke defense postures in the normal rats paired with them; however, apomorphine partially mimicked the delta9-THC-effects. It is concluded that in REM-deprived rats delta9-THC not only provokes aggressive behavior but also impairs the defensive-submissive behavioral patterns."}
{"id": "PMID:197558", "title": "The effects of various protein synthesis inhibitors on the sleep-wake cycle of rats.", "content": "The present investigation sought to determine the effects of Anisomycin (A), Chloramphenicol (ChA), Vincristine (V), and Penicilline G on the sleep-wake cycle of rats. It was found that both high and low doses of anisomycin decreased rapid eye movement (REM) sleep, while only high doses of ChA and V produced such a decrease. Slow wave sleep (SWS) was unaffected by these drugs. Penicilline G, on the other hand, had no effect on the sleep-wake cycle. It was further shown that the reduction of REM sleep was the result of a decrease in the number of REM periods rather than in the duration of each individual period. These results suggest that protein synthesis may participate in the mechanisms that trigger REM sleep.", "contents": "The effects of various protein synthesis inhibitors on the sleep-wake cycle of rats. The present investigation sought to determine the effects of Anisomycin (A), Chloramphenicol (ChA), Vincristine (V), and Penicilline G on the sleep-wake cycle of rats. It was found that both high and low doses of anisomycin decreased rapid eye movement (REM) sleep, while only high doses of ChA and V produced such a decrease. Slow wave sleep (SWS) was unaffected by these drugs. Penicilline G, on the other hand, had no effect on the sleep-wake cycle. It was further shown that the reduction of REM sleep was the result of a decrease in the number of REM periods rather than in the duration of each individual period. These results suggest that protein synthesis may participate in the mechanisms that trigger REM sleep."}
{"id": "PMID:197559", "title": "Impairment of retention of avoidance responses in rats by posttraining diethyldithiocarbamate.", "content": "Diethyldithiocarbamate (680 mg/kg), administered immediately after training, impaired rats' retention, 6 days later, of a one-way active avoidance task and a discriminated active avoidance task. In the discrimination task a lower dose (340 mg/kg) also impaired retention. Delayed posttraining injections did not affect retention in either task. The findings indicate that DDC can have similar effects on retention of tasks requiring quite different behavioral responses.", "contents": "Impairment of retention of avoidance responses in rats by posttraining diethyldithiocarbamate. Diethyldithiocarbamate (680 mg/kg), administered immediately after training, impaired rats' retention, 6 days later, of a one-way active avoidance task and a discriminated active avoidance task. In the discrimination task a lower dose (340 mg/kg) also impaired retention. Delayed posttraining injections did not affect retention in either task. The findings indicate that DDC can have similar effects on retention of tasks requiring quite different behavioral responses."}
{"id": "PMID:197562", "title": "Physiological studies on facial reflexes in the rat.", "content": "Experiments were performed on 36 male albino rats anaesthetized with pentobarbitone sodium and paralyzed with gallamine triethiodide. Recordings were made with single and multibarrel glass microelectrodes in the facial nucleus and monopolar silver wire electrodes on the lingual, facial, glossopharyngeal and hypoglossal nerves. The absolute refractory period for facial motoneurones is 2-3 ms, the relative refractory period has a duration of 26-34 ms and the range in axonal conduction velocities is from 15 to 45 m.sec-1. No evidence for afferent fibres in the muscle branches of the facial and hypoglassal nerves could be found. The lingual and glossopharyngeal nerves show reflex connexions with both the facial and hypoglassal nerves. The time courses of the potentiations and depressions of test facial antidromic field potentials following lingual and glossopharyngeal conditioning stimuli are given. Evoked synaptic activity and the distribution of field potentials in the facial mucleus following lingual and glossopharyngeal nerve stimulation are also described. The observed lingual and glossopharyngeal-facial reflexes are discussed with respect to blink reflexes.", "contents": "Physiological studies on facial reflexes in the rat. Experiments were performed on 36 male albino rats anaesthetized with pentobarbitone sodium and paralyzed with gallamine triethiodide. Recordings were made with single and multibarrel glass microelectrodes in the facial nucleus and monopolar silver wire electrodes on the lingual, facial, glossopharyngeal and hypoglossal nerves. The absolute refractory period for facial motoneurones is 2-3 ms, the relative refractory period has a duration of 26-34 ms and the range in axonal conduction velocities is from 15 to 45 m.sec-1. No evidence for afferent fibres in the muscle branches of the facial and hypoglassal nerves could be found. The lingual and glossopharyngeal nerves show reflex connexions with both the facial and hypoglassal nerves. The time courses of the potentiations and depressions of test facial antidromic field potentials following lingual and glossopharyngeal conditioning stimuli are given. Evoked synaptic activity and the distribution of field potentials in the facial mucleus following lingual and glossopharyngeal nerve stimulation are also described. The observed lingual and glossopharyngeal-facial reflexes are discussed with respect to blink reflexes."}
{"id": "PMID:197563", "title": "Investigations on radical formation and inactivation of suspended trypsin after gamma-irradiation.", "content": "Crystalline trypsin was irradiated in oxygen-free suspension media of methanol, ethanol and n-heptane with 60Co-gamma-rays at 77 K or 273 K. Measurements with ESR and activity determinations revealed no influence of ethanol and n-heptane on the formation of free radicals and inactivation of trypsin. Especially, the results are independent on the polarity of the suspension media and correspond to an irradiation of trypsin in vacuum. On the other hand, methanol leads to a decay of radiation induced radicals and to an increased inactivation. The results are discussed in comparison to analogous experiments carried out with ultra-violet light.", "contents": "Investigations on radical formation and inactivation of suspended trypsin after gamma-irradiation. Crystalline trypsin was irradiated in oxygen-free suspension media of methanol, ethanol and n-heptane with 60Co-gamma-rays at 77 K or 273 K. Measurements with ESR and activity determinations revealed no influence of ethanol and n-heptane on the formation of free radicals and inactivation of trypsin. Especially, the results are independent on the polarity of the suspension media and correspond to an irradiation of trypsin in vacuum. On the other hand, methanol leads to a decay of radiation induced radicals and to an increased inactivation. The results are discussed in comparison to analogous experiments carried out with ultra-violet light."}
{"id": "PMID:197560", "title": "An integrative model for the treatment of psychosomatic disorders. The place of sleep and dreams revisited.", "content": "The functions and dysfunctions of slow wave sleep and of REM sleep and its associated dreams have a tremendous significance in understanding the psychosomatic model of illness and in establishing preventive strategies. Ten patients suffering from a variety of psychosomatic illnessess spent 3-4 nights sleeping at the Dream Laboratory. A psychiatric evaluation was carried out and those suffering from schizophrenia, severe depression, acute stage of physical illness and organic deficits were not accepted for the study. It was postulated that increased psychosomatic 'penetrance' as measured by poverty of fantasy life, feelings of helplessness, absence of dream reports, vacant and contrived emotional expression and poor psychological mindedness would be correlated with psychological test results (IPAT anxiety Scale and Zung Depression Rating Scale), manifest dream content analysis and particular REM and stage 4 deficit. The higher psychosomatic 'penetrance' in our study was not found in all patients with a psychosomatic diagnosis but rather in those patients suffering from ulcerative colitis. The degree of 'penetrance' was related to specific physiological, psychological and interpersonal parameters. Based on these findings a spectrum of clinical and physiological criteria of selection for particular therapeutic intervention was presented.", "contents": "An integrative model for the treatment of psychosomatic disorders. The place of sleep and dreams revisited. The functions and dysfunctions of slow wave sleep and of REM sleep and its associated dreams have a tremendous significance in understanding the psychosomatic model of illness and in establishing preventive strategies. Ten patients suffering from a variety of psychosomatic illnessess spent 3-4 nights sleeping at the Dream Laboratory. A psychiatric evaluation was carried out and those suffering from schizophrenia, severe depression, acute stage of physical illness and organic deficits were not accepted for the study. It was postulated that increased psychosomatic 'penetrance' as measured by poverty of fantasy life, feelings of helplessness, absence of dream reports, vacant and contrived emotional expression and poor psychological mindedness would be correlated with psychological test results (IPAT anxiety Scale and Zung Depression Rating Scale), manifest dream content analysis and particular REM and stage 4 deficit. The higher psychosomatic 'penetrance' in our study was not found in all patients with a psychosomatic diagnosis but rather in those patients suffering from ulcerative colitis. The degree of 'penetrance' was related to specific physiological, psychological and interpersonal parameters. Based on these findings a spectrum of clinical and physiological criteria of selection for particular therapeutic intervention was presented."}
{"id": "PMID:197564", "title": "Biological damage in testis by iodine-125 in partially blocked thyroid of rats.", "content": "Degeneration of testis has been observed after administration of Iodine-125 in potassiumperchlorate treated rats. Histological damage is associated with loss of DNA, RNA, acid phosphatase, total adenosine triphosphatase (ATPase) and Na/K dependent ATPase. Iodine-125 induced atrophic testis shows higher content of sodium and lower levels of potassium as compared to control testis. Damage of testis by Iodine-125 has been compared with atrophied testis, following gamma irradiation earlier reported. Auger effect due to Iodine-125 decay and transmutation at the sites of nuclei and plasma membrane of germinal cells seems to be the possible explanation for testicular damage caused by Iodine-125.", "contents": "Biological damage in testis by iodine-125 in partially blocked thyroid of rats. Degeneration of testis has been observed after administration of Iodine-125 in potassiumperchlorate treated rats. Histological damage is associated with loss of DNA, RNA, acid phosphatase, total adenosine triphosphatase (ATPase) and Na/K dependent ATPase. Iodine-125 induced atrophic testis shows higher content of sodium and lower levels of potassium as compared to control testis. Damage of testis by Iodine-125 has been compared with atrophied testis, following gamma irradiation earlier reported. Auger effect due to Iodine-125 decay and transmutation at the sites of nuclei and plasma membrane of germinal cells seems to be the possible explanation for testicular damage caused by Iodine-125."}
{"id": "PMID:197566", "title": "Tomography in expansile lesions of the nasal and paranasal sinuses.", "content": "Of 35 nasal and paranasal sinus masses examined by radiography and tomography, 22 malignant tumors showed purely destructive growth. Bone expansion was observed in 13 benign, and 2 slowly growing malignant masses. Pluridirectional tomography in carefully selected projections is often necessary to reveal expansile growth. The 13 expansile lesions, including mucocele, neurofibroma, dermoid, epidermoid, cementifying fibroma, angiofibroma, inverting papilloma, and cylindroma, are briefly described. Tomographic appearance alone did not characterize histopathologic entities. However, distinctions may be made between fibro-osseous and epithelial tumors, and between fast growing and slowly growing tumors.", "contents": "Tomography in expansile lesions of the nasal and paranasal sinuses. Of 35 nasal and paranasal sinus masses examined by radiography and tomography, 22 malignant tumors showed purely destructive growth. Bone expansion was observed in 13 benign, and 2 slowly growing malignant masses. Pluridirectional tomography in carefully selected projections is often necessary to reveal expansile growth. The 13 expansile lesions, including mucocele, neurofibroma, dermoid, epidermoid, cementifying fibroma, angiofibroma, inverting papilloma, and cylindroma, are briefly described. Tomographic appearance alone did not characterize histopathologic entities. However, distinctions may be made between fibro-osseous and epithelial tumors, and between fast growing and slowly growing tumors."}
{"id": "PMID:197567", "title": "Radiation sensitivity of cultured human glioblastoma cells.", "content": "Glial cells from 2 normal brains and 9 astrocytomas were cultured in vitro. The most rapidly proliferating cell lines were obtained from Grades III-IV astrocytomas. Normal glia proliferated slowly and growth ceased after 20 to 40 generations. The response of 3 Grade III-IV lines to graded doses of radiation was determined by colony formation and end point dilution technique. Two of the 3 lines were relatively radioresistant compared to other human cell lines; this may partially account for the radiation resistance of high grade astrocytoma tumors.", "contents": "Radiation sensitivity of cultured human glioblastoma cells. Glial cells from 2 normal brains and 9 astrocytomas were cultured in vitro. The most rapidly proliferating cell lines were obtained from Grades III-IV astrocytomas. Normal glia proliferated slowly and growth ceased after 20 to 40 generations. The response of 3 Grade III-IV lines to graded doses of radiation was determined by colony formation and end point dilution technique. Two of the 3 lines were relatively radioresistant compared to other human cell lines; this may partially account for the radiation resistance of high grade astrocytoma tumors."}
{"id": "PMID:197569", "title": "Stimulation of ACTH secretion by indomethacin and reversal by exogenous prostaglandins.", "content": "The prostaglandin (PG) synthesis inhibitor, indomethacin, has been found to enhance adrenocorticotropin (ACTH) secretion upon injection directly into the anterior pituitary at a dose that is ineffective intravenously. Such stimulation was observed in combination with, and in the absence of, stimulation by a corticotropin-releasing factor (CRF) preparation. It was reversed to varying degrees by replacing certain PGs exogenously. It suggested that endogenous PGs in the anterior pituitary participate in the modulation of the sensitivity of this gland to the hypothalamic neurohormone, CRF.", "contents": "Stimulation of ACTH secretion by indomethacin and reversal by exogenous prostaglandins. The prostaglandin (PG) synthesis inhibitor, indomethacin, has been found to enhance adrenocorticotropin (ACTH) secretion upon injection directly into the anterior pituitary at a dose that is ineffective intravenously. Such stimulation was observed in combination with, and in the absence of, stimulation by a corticotropin-releasing factor (CRF) preparation. It was reversed to varying degrees by replacing certain PGs exogenously. It suggested that endogenous PGs in the anterior pituitary participate in the modulation of the sensitivity of this gland to the hypothalamic neurohormone, CRF."}
{"id": "PMID:197570", "title": "Cyclic AMP and platelet prostaglandin synthesis.", "content": "The present study has investigated the influence of agents which elevate intracellular levels of endogenous platelet adenosine 3'5'-cyclic monophosphate (cyclic AMP), and the effect of the exogenous cyclic AMP analog, dibutyryl cyclic AMP, on the conversion of 14C-arachidonic acid by washed platelets. Prostaglandin E1 (PGE1), PGE1 with theophylline, or dibutyryl cyclic AMP incubated with washed platelets prevented arachidonic acid induced platelet aggregation, but had no effect on the conversion of arachidonic acid to 12L-hydroxy-5,8,10, 14-eicosatetraenoic acid (HETE), 12L-hydroxy-5,8,10 heptadecatrienoic acid (HHT), or thromboxane B2. Ultrastructural studies of the platelet response revealed that agents acting directly or indirectly to increase the level of cyclic AMP inhibited the action of arachidonic acid on washed platelets and prevented internal platelet contraction as well as aggregation. The influence of PGE1 with theophylline, and dibutyryl cyclic AMP on the thrombin induced release of 14C-arachidonic acid from platelet membrane phospholipids was also investigated. These agents were found to be potent inhibitors of the thrombin stimulated release of arachidonic acid from platelet phospholipids, due most likely to an inhibition of platelet phospholipase A activity. The results show that dibutyryl cyclic AMP and agents which elevate intracellular cyclic AMP levels act to inhibit platelet activation at two steps 1) internal contraction and 2) release of arachidonic acid from platelet phospholipids.", "contents": "Cyclic AMP and platelet prostaglandin synthesis. The present study has investigated the influence of agents which elevate intracellular levels of endogenous platelet adenosine 3'5'-cyclic monophosphate (cyclic AMP), and the effect of the exogenous cyclic AMP analog, dibutyryl cyclic AMP, on the conversion of 14C-arachidonic acid by washed platelets. Prostaglandin E1 (PGE1), PGE1 with theophylline, or dibutyryl cyclic AMP incubated with washed platelets prevented arachidonic acid induced platelet aggregation, but had no effect on the conversion of arachidonic acid to 12L-hydroxy-5,8,10, 14-eicosatetraenoic acid (HETE), 12L-hydroxy-5,8,10 heptadecatrienoic acid (HHT), or thromboxane B2. Ultrastructural studies of the platelet response revealed that agents acting directly or indirectly to increase the level of cyclic AMP inhibited the action of arachidonic acid on washed platelets and prevented internal platelet contraction as well as aggregation. The influence of PGE1 with theophylline, and dibutyryl cyclic AMP on the thrombin induced release of 14C-arachidonic acid from platelet membrane phospholipids was also investigated. These agents were found to be potent inhibitors of the thrombin stimulated release of arachidonic acid from platelet phospholipids, due most likely to an inhibition of platelet phospholipase A activity. The results show that dibutyryl cyclic AMP and agents which elevate intracellular cyclic AMP levels act to inhibit platelet activation at two steps 1) internal contraction and 2) release of arachidonic acid from platelet phospholipids."}
{"id": "PMID:197571", "title": "Synthesis of thromboxane A2 by non-aggregating dog platelets challenged with arachidonic acid or with prostaglandin H2.", "content": "Dog platelets challenged with arachidonic acid fail to aggregate but synthesize a substance which aggregates rabbit and human platelets, this aggregation being suppressed by dibutyryl cyclic AMP. The aggregating substance contracts strips of rabbit aorta and of coeliac and mesenteric arteries, is soluble in diethyl ether, has a half-life of about 40 seconds at 37 degrees C and of 100 seconds at 22 degrees C. Its generation is blocked by various inhibitors of prostaglandin biosynthesis. The thromboxane A2 synthetase inhibitor imidazole and its analogue benzimidazolamine also suppress generation of vessel contracting activity in incubates of dog platelets and prostaglandin H2. Since dog platelets also transform prostaglandin H2 into thromboxane A2 their failure to aggregate, when stimulated by arachidonic acid or by prostaglandin H2, is not due to lack of thromboxane synthesizing ability.", "contents": "Synthesis of thromboxane A2 by non-aggregating dog platelets challenged with arachidonic acid or with prostaglandin H2. Dog platelets challenged with arachidonic acid fail to aggregate but synthesize a substance which aggregates rabbit and human platelets, this aggregation being suppressed by dibutyryl cyclic AMP. The aggregating substance contracts strips of rabbit aorta and of coeliac and mesenteric arteries, is soluble in diethyl ether, has a half-life of about 40 seconds at 37 degrees C and of 100 seconds at 22 degrees C. Its generation is blocked by various inhibitors of prostaglandin biosynthesis. The thromboxane A2 synthetase inhibitor imidazole and its analogue benzimidazolamine also suppress generation of vessel contracting activity in incubates of dog platelets and prostaglandin H2. Since dog platelets also transform prostaglandin H2 into thromboxane A2 their failure to aggregate, when stimulated by arachidonic acid or by prostaglandin H2, is not due to lack of thromboxane synthesizing ability."}
{"id": "PMID:197573", "title": "Glucose-6-phosphatase inactivation and peroxidation of phosphatidylcholine in microsomal membranes.", "content": "Peroxidation induced by ascorbate on phospholipids of isolated rat liver microsomes were accompanied by losses in glucose-6-phosphatase activity (EC 3.1.3.9.). The existence of marked differences in the degradation rate for each phospholipid suggests a relationship between the alteration of phosphatidylcholine containing one saturated and one unsaturated fatty acid and the decrease in activity of glucose-6-phosphatase; the inactivation of this enzyme was unrelated to the alteration of other phospholipids. These results support the idea that glucose-6-phosphatase and molecules of phosphatidylcholine having one saturated and one unsaturated fatty acid are in close apposition within the microsomal membrane.", "contents": "Glucose-6-phosphatase inactivation and peroxidation of phosphatidylcholine in microsomal membranes. Peroxidation induced by ascorbate on phospholipids of isolated rat liver microsomes were accompanied by losses in glucose-6-phosphatase activity (EC 3.1.3.9.). The existence of marked differences in the degradation rate for each phospholipid suggests a relationship between the alteration of phosphatidylcholine containing one saturated and one unsaturated fatty acid and the decrease in activity of glucose-6-phosphatase; the inactivation of this enzyme was unrelated to the alteration of other phospholipids. These results support the idea that glucose-6-phosphatase and molecules of phosphatidylcholine having one saturated and one unsaturated fatty acid are in close apposition within the microsomal membrane."}
{"id": "PMID:197574", "title": "NADH-cytochrome c reductase, succinate cytochrome c reductase and phospholipids.", "content": "Phospholipid peroxidation of isolated rat liver inner mitochondrial membranes induced by either ascorbate or cysteine was accompanied by a release of flavins and coenzyme Q. A straight correlation between this release and the alteration of molecular species of phosphatidylcholine and phosphatidylethanolamine containing one saturated and one unsaturated fatty acid has been found. Peroxidation induced on molecular species of phosphatidylcholine and phosphatidylethanolamine containing only unsaturated fatty acids were accompanied by losses in enzyme activities of NADH-cytochrome c reductase and succinate cytochrome c reductase.", "contents": "NADH-cytochrome c reductase, succinate cytochrome c reductase and phospholipids. Phospholipid peroxidation of isolated rat liver inner mitochondrial membranes induced by either ascorbate or cysteine was accompanied by a release of flavins and coenzyme Q. A straight correlation between this release and the alteration of molecular species of phosphatidylcholine and phosphatidylethanolamine containing one saturated and one unsaturated fatty acid has been found. Peroxidation induced on molecular species of phosphatidylcholine and phosphatidylethanolamine containing only unsaturated fatty acids were accompanied by losses in enzyme activities of NADH-cytochrome c reductase and succinate cytochrome c reductase."}
{"id": "PMID:197575", "title": "A rapid and simple radioactive method for the determination of disulfiram and its metabolites from a single sample of biological fluid or tissue.", "content": "An analytical method is described for the determination of radioactive disulfiram, diethyldithiocarbamate, diethyldithiocarbamate-methyl ester, diethyldithiocarbamate-glucuronide, inorganic sulfate, and a protein bound S35 fraction from a single sample of either plasma, urine or tissue. The procedure is based upon quantitative stepwise extraction or precipitation of the individual compounds, and is both specific and precise. The applicability of the methods developed for the determination of S35 disulfiram and its S35 metabolites in plasma and urine from a dog given S35 disulfiram i.v., and in mouse brain from mice given S35 disulfiram i.p. are illustrated.", "contents": "A rapid and simple radioactive method for the determination of disulfiram and its metabolites from a single sample of biological fluid or tissue. An analytical method is described for the determination of radioactive disulfiram, diethyldithiocarbamate, diethyldithiocarbamate-methyl ester, diethyldithiocarbamate-glucuronide, inorganic sulfate, and a protein bound S35 fraction from a single sample of either plasma, urine or tissue. The procedure is based upon quantitative stepwise extraction or precipitation of the individual compounds, and is both specific and precise. The applicability of the methods developed for the determination of S35 disulfiram and its S35 metabolites in plasma and urine from a dog given S35 disulfiram i.v., and in mouse brain from mice given S35 disulfiram i.p. are illustrated."}
{"id": "PMID:197577", "title": "[Peptidyl prolyl hydroxylase activity in relation to the actual collagen biosynthesis in cotton pellet granuloma of guinea pig (author's transl)].", "content": "During the different stages of granuloma formation peptidyl prolyl hydroxylase activity and neutral salt soluble collagen were determined in the granuloma tissue. In parallel peptidyl prolyl hydroxylase activity, \"collagen-like protein\", and free hydroxyproline were measured in the serum of the same animals at correspondant time distances. A close correlation was found between the enzyme activity and the other parameters of collagen synthesis. These results confirm the conclusion that hydroxylation of polypeptide may be a rate limiting step in collagen biosynthesis. In addition the investigations revealed a close correlation between enzyme activity in the tissue and enzyme activity in the serum.", "contents": "[Peptidyl prolyl hydroxylase activity in relation to the actual collagen biosynthesis in cotton pellet granuloma of guinea pig (author's transl)]. During the different stages of granuloma formation peptidyl prolyl hydroxylase activity and neutral salt soluble collagen were determined in the granuloma tissue. In parallel peptidyl prolyl hydroxylase activity, \"collagen-like protein\", and free hydroxyproline were measured in the serum of the same animals at correspondant time distances. A close correlation was found between the enzyme activity and the other parameters of collagen synthesis. These results confirm the conclusion that hydroxylation of polypeptide may be a rate limiting step in collagen biosynthesis. In addition the investigations revealed a close correlation between enzyme activity in the tissue and enzyme activity in the serum."}
{"id": "PMID:197589", "title": "The extracellular release of granulocyte collagenase and elastase during phagocytosis and inflammatory processes.", "content": "Human granulocytes release 25-30% of the granular neutral proteases, collagenase and elastase, to the exterior of the cell during phagocytosis of yeast cells or immune complexes. Similar amounts of myeloperoxidase and lactoferrin are released. Crossed immunoelectrophoresis demonstrated that collagenase and elastase released extracellularly formed complexes with serum alpha1-antitrypsin. The presence of alpha1-antitrypsin complexes with granulocyte collagenase and elastase were also demonstrated in inflammatory processes, e.g. in the peritoneal exudate of acute peritonitis. The reactivity of neutrophil proteases with natural plasma protease inhibitors must be considered in assessing the role of these proteases as the etiologic agent of tissue damage and degradation during the inflammatory process.", "contents": "The extracellular release of granulocyte collagenase and elastase during phagocytosis and inflammatory processes. Human granulocytes release 25-30% of the granular neutral proteases, collagenase and elastase, to the exterior of the cell during phagocytosis of yeast cells or immune complexes. Similar amounts of myeloperoxidase and lactoferrin are released. Crossed immunoelectrophoresis demonstrated that collagenase and elastase released extracellularly formed complexes with serum alpha1-antitrypsin. The presence of alpha1-antitrypsin complexes with granulocyte collagenase and elastase were also demonstrated in inflammatory processes, e.g. in the peritoneal exudate of acute peritonitis. The reactivity of neutrophil proteases with natural plasma protease inhibitors must be considered in assessing the role of these proteases as the etiologic agent of tissue damage and degradation during the inflammatory process."}
{"id": "PMID:197590", "title": "Elevated serum ferritin in children with malignancies.", "content": "Serum ferritin (SF) is elevated in adults with malignancies, chronic inflammatory disease, liver disease and iron overload. The purpose of this study was to determine whether the concentration of SF in children with a variety of malignancies correlated with the activity of their disease. Patients with acute lymphoblastic leukaemia (ALL) at initial diagnosis (n = 11) and relapse (n = 15) had a mean SF of 238 and 338 ng/ml, respectively, compared to the normal mean of 31 ng/ml and range of 7 to 140 ng/ml in children. In 30 patients with ALL in remission the mean SF was 109 ng/ml, less than the values in patients with active disease and greater than the normal mean (P less than 0.001). The concentration of SF was also increased in a group of 77 patients with a variety of solid tumors. The 28 cases with active disease had a mean SF of 242 ng/ml, significantly higher (P less than 0.001) that the value of 84 ng/ml in 49 patients with no evidence of residual tumor. The differences in SF concentration did reflect the activity of disease in the groups as a whole but it remains uncertain whether the assay will prove useful in following the response to treatment of patients with certain types of tumor.", "contents": "Elevated serum ferritin in children with malignancies. Serum ferritin (SF) is elevated in adults with malignancies, chronic inflammatory disease, liver disease and iron overload. The purpose of this study was to determine whether the concentration of SF in children with a variety of malignancies correlated with the activity of their disease. Patients with acute lymphoblastic leukaemia (ALL) at initial diagnosis (n = 11) and relapse (n = 15) had a mean SF of 238 and 338 ng/ml, respectively, compared to the normal mean of 31 ng/ml and range of 7 to 140 ng/ml in children. In 30 patients with ALL in remission the mean SF was 109 ng/ml, less than the values in patients with active disease and greater than the normal mean (P less than 0.001). The concentration of SF was also increased in a group of 77 patients with a variety of solid tumors. The 28 cases with active disease had a mean SF of 242 ng/ml, significantly higher (P less than 0.001) that the value of 84 ng/ml in 49 patients with no evidence of residual tumor. The differences in SF concentration did reflect the activity of disease in the groups as a whole but it remains uncertain whether the assay will prove useful in following the response to treatment of patients with certain types of tumor."}
{"id": "PMID:197591", "title": "Modeling and computer stimulation approach to the mechanism of foot-and-mouth disease virus neutralization assays.", "content": "Block neutralization data since 1949 for the foot-and-mouth disease virus system have been analyzed in terms of a unified mass-action theory for computing the amounts of infectious complexes. Proof that infectious complexes contribute considerably to the assays was obtained by demonstrating a reduction in titer after an additional reaction with anti-Ig antibody before the assay. In the suckling-mice assay with intraperitoneal inoculation, both the data of others and our own on several types indicate that for IgG probably three of the unknown total number of critical sites on the virion must be available for infectivity and death. For IgM, just one of an unknown different total number of critical sites on the virion must be available. In tissue culture infectivity assays the minimum number is two or three, whereas in the bovine tongue assay it could be one or two, but probably two. The difficulties in establishing the at present unknown total numbers of neutralization sites to both IgG and IgM are considerable. However, by the simplest interpretation of the data, the number is estimated to be between 5 and 10 for IgG and perhaps just 1 for IgM. A speculation, consistent with the known virion architecture, is that just 1 of the 12 vertices is uniquely involved in infectivity and death, at least in the suckling-mice assay.", "contents": "Modeling and computer stimulation approach to the mechanism of foot-and-mouth disease virus neutralization assays. Block neutralization data since 1949 for the foot-and-mouth disease virus system have been analyzed in terms of a unified mass-action theory for computing the amounts of infectious complexes. Proof that infectious complexes contribute considerably to the assays was obtained by demonstrating a reduction in titer after an additional reaction with anti-Ig antibody before the assay. In the suckling-mice assay with intraperitoneal inoculation, both the data of others and our own on several types indicate that for IgG probably three of the unknown total number of critical sites on the virion must be available for infectivity and death. For IgM, just one of an unknown different total number of critical sites on the virion must be available. In tissue culture infectivity assays the minimum number is two or three, whereas in the bovine tongue assay it could be one or two, but probably two. The difficulties in establishing the at present unknown total numbers of neutralization sites to both IgG and IgM are considerable. However, by the simplest interpretation of the data, the number is estimated to be between 5 and 10 for IgG and perhaps just 1 for IgM. A speculation, consistent with the known virion architecture, is that just 1 of the 12 vertices is uniquely involved in infectivity and death, at least in the suckling-mice assay."}
{"id": "PMID:197592", "title": "Cytomegalovirus infection associated with severe encephalitis.", "content": "A previously healthy 37-year-old woman had a 5-week febrile disease starting 10 days after delivery, which was complicated by disseminated intravascular coagulation and treated with fresh blood transfusions. She developed severe encephalitis with coma. She also had signs of perimyocarditis and enlargement of liver and lymph nodes. The encephalitis was completely reversible. There was a 16-fold rise in complement-fixing antibodies against cytomegalovirus.", "contents": "Cytomegalovirus infection associated with severe encephalitis. A previously healthy 37-year-old woman had a 5-week febrile disease starting 10 days after delivery, which was complicated by disseminated intravascular coagulation and treated with fresh blood transfusions. She developed severe encephalitis with coma. She also had signs of perimyocarditis and enlargement of liver and lymph nodes. The encephalitis was completely reversible. There was a 16-fold rise in complement-fixing antibodies against cytomegalovirus."}
{"id": "PMID:197593", "title": "Use of purified cytomegalovirus as antigen in the complememt fixation test.", "content": "Crude cytomegalovirus (CMV) antigen and purified CMV antigen were used in tests for complement-fixating (CF) antibodies in sera from 7 patients with CMV infection. CF antibodies to purified CMV appeared later than the other CF antibodies tested and parallel to neutralizing antibodies.", "contents": "Use of purified cytomegalovirus as antigen in the complememt fixation test. Crude cytomegalovirus (CMV) antigen and purified CMV antigen were used in tests for complement-fixating (CF) antibodies in sera from 7 patients with CMV infection. CF antibodies to purified CMV appeared later than the other CF antibodies tested and parallel to neutralizing antibodies."}
{"id": "PMID:197594", "title": "Antibodies to human coronavirus OC43 measured by radial haemolysis in gel.", "content": "An application of the haemolysis-in-gel (HIG) technique was developed to quantitate antibodies against the human coronavirus OC43. Preinfection and convalescent sera from two patients with verified OC43 infection showed a significant increase in antibody titres measured by HIG as well as by haemagglutination-inhibition (HI). 241 of the other 306 sera tested (80%) caused radial haemolysis in gels containing viral antigen-sensitized erythrocytes and complement. No haemolysis was seen in gels prepared with unifected material. Correlation of the diameter of the haemolysis ring to the respective HI titre was highly significant. However, 62 sera (20%) with HI titres between 8 and 320 were negative in the HIG. Attempts to show that these sera contained nonspecific inhibitors of haemagglutination were unsuccessful. OC43 HI and HIG probably measure different antibody ppulations.", "contents": "Antibodies to human coronavirus OC43 measured by radial haemolysis in gel. An application of the haemolysis-in-gel (HIG) technique was developed to quantitate antibodies against the human coronavirus OC43. Preinfection and convalescent sera from two patients with verified OC43 infection showed a significant increase in antibody titres measured by HIG as well as by haemagglutination-inhibition (HI). 241 of the other 306 sera tested (80%) caused radial haemolysis in gels containing viral antigen-sensitized erythrocytes and complement. No haemolysis was seen in gels prepared with unifected material. Correlation of the diameter of the haemolysis ring to the respective HI titre was highly significant. However, 62 sera (20%) with HI titres between 8 and 320 were negative in the HIG. Attempts to show that these sera contained nonspecific inhibitors of haemagglutination were unsuccessful. OC43 HI and HIG probably measure different antibody ppulations."}
{"id": "PMID:197595", "title": "Uptake of 5(125I) iodo-2-deoxyuridine (IDU) in plasma and cerebrospinal fluid in a case of herpes encephalitis with a comparative study on the uptake in plasma, cerebrospinal fluid and brain tissue in dogs.", "content": "A case of herpes encephalitis diagnosed by brain biopsy and treated with 5-iodo-2-deoxyuridine (IDU) is presented. The infection occurred in a previously well 19-year-old female patient. Plasma and cerebrospinal fluid (CSF) uptake of the substance was determined using 125I labelled IDU. Top CSF levels of IUD and metabolites of less than 4 microgram/ml, about 1/10 of the corresponding plasma level, were obtained after 6 hours of continuous infusion. The result is discussed and compared with a similar study made on 5 healthy beagle dogs where in addition the levels obtained in various parts of the brain were determined. In the animal experiment a mean value of 2.5 microgram/ml of IDU and metabolites was obtained in the CSF after 8 hours, less than 1/20 of the plasma level. The levels in brain tissue were only slightly higher than in the CSF. The causes of therapeutic failures with IDU treatment are discussed.", "contents": "Uptake of 5(125I) iodo-2-deoxyuridine (IDU) in plasma and cerebrospinal fluid in a case of herpes encephalitis with a comparative study on the uptake in plasma, cerebrospinal fluid and brain tissue in dogs. A case of herpes encephalitis diagnosed by brain biopsy and treated with 5-iodo-2-deoxyuridine (IDU) is presented. The infection occurred in a previously well 19-year-old female patient. Plasma and cerebrospinal fluid (CSF) uptake of the substance was determined using 125I labelled IDU. Top CSF levels of IUD and metabolites of less than 4 microgram/ml, about 1/10 of the corresponding plasma level, were obtained after 6 hours of continuous infusion. The result is discussed and compared with a similar study made on 5 healthy beagle dogs where in addition the levels obtained in various parts of the brain were determined. In the animal experiment a mean value of 2.5 microgram/ml of IDU and metabolites was obtained in the CSF after 8 hours, less than 1/20 of the plasma level. The levels in brain tissue were only slightly higher than in the CSF. The causes of therapeutic failures with IDU treatment are discussed."}
{"id": "PMID:197596", "title": "Distubed neuromuscular transmission in viral infections.", "content": "14 subjects with influenza or echovirus infection, all suffering myalgia, and 9 subjects with mumps, in whom this symptom was lacking, were investigated with single fibre electromyography (EMG) in the acute phase and during convalescence to reveal a possible disturbance in neuromuscular transmission. In both groups about the same percentage of the potential pairs studied showed abnormal transmission characteristics in the acute phase. Two weeks after the acute infection, this percentage had decreased significantly in the group with myalgia, whilst in the non-myalgia group it was still at the same level. However, on both occasions of investigation and in both groups the percentages were substantially greater than those recorded in healthy individuals. This study demonstrates that acute febrile infections may adversely affect neuromuscular transmission in previously healthy human subjects. The effects observed might offer an explanation to the accentuated muscular weakness in association with infections in patients with an already low safety margion of neuromuscular transmission, e.g. in myasthenia gravis.", "contents": "Distubed neuromuscular transmission in viral infections. 14 subjects with influenza or echovirus infection, all suffering myalgia, and 9 subjects with mumps, in whom this symptom was lacking, were investigated with single fibre electromyography (EMG) in the acute phase and during convalescence to reveal a possible disturbance in neuromuscular transmission. In both groups about the same percentage of the potential pairs studied showed abnormal transmission characteristics in the acute phase. Two weeks after the acute infection, this percentage had decreased significantly in the group with myalgia, whilst in the non-myalgia group it was still at the same level. However, on both occasions of investigation and in both groups the percentages were substantially greater than those recorded in healthy individuals. This study demonstrates that acute febrile infections may adversely affect neuromuscular transmission in previously healthy human subjects. The effects observed might offer an explanation to the accentuated muscular weakness in association with infections in patients with an already low safety margion of neuromuscular transmission, e.g. in myasthenia gravis."}
{"id": "PMID:197598", "title": "[Sharp's syndrome (mixed connective tissue disease). Clinical aspects diagnosis and prognosis].", "content": "Sharp syndrome (mixed connective tissue disease) is a distinct rheumatic syndrome with symptoms of various connective tissue diseases (rheumatoid arthritis, systemic lupus erythematodes, progressive systemic sclerosis, polymyositis and others). 15 patients with mixed connective tissue disease are described. The clinical picture and diagnostic criteria are evaluated and the course of the disease, treatment and prognosis are discussed.", "contents": "[Sharp's syndrome (mixed connective tissue disease). Clinical aspects diagnosis and prognosis]. Sharp syndrome (mixed connective tissue disease) is a distinct rheumatic syndrome with symptoms of various connective tissue diseases (rheumatoid arthritis, systemic lupus erythematodes, progressive systemic sclerosis, polymyositis and others). 15 patients with mixed connective tissue disease are described. The clinical picture and diagnostic criteria are evaluated and the course of the disease, treatment and prognosis are discussed."}
{"id": "PMID:197600", "title": "Adenine and adenosine are toxic to human lymphoblast mutants defective in purine salvage enzymes.", "content": "Mutants deficient in adenosine kinase or adenine phosphoribosyltransferase activities were selected from the WI-L2 line of human lymphoblasts. The adenosine kinase-deficient mutant was still as sensitive as its parent to growth inhibition caused by adenosine deaminase was inhibited. Similarly, the adenine phosphoribosyltransferase mutant remained sensitive to growth inhibition caused by adenine. Thus, the toxicity of adenine and adenosine to human lymphoblasts is not mediated by nucleotides to which they may be converted.", "contents": "Adenine and adenosine are toxic to human lymphoblast mutants defective in purine salvage enzymes. Mutants deficient in adenosine kinase or adenine phosphoribosyltransferase activities were selected from the WI-L2 line of human lymphoblasts. The adenosine kinase-deficient mutant was still as sensitive as its parent to growth inhibition caused by adenosine deaminase was inhibited. Similarly, the adenine phosphoribosyltransferase mutant remained sensitive to growth inhibition caused by adenine. Thus, the toxicity of adenine and adenosine to human lymphoblasts is not mediated by nucleotides to which they may be converted."}
{"id": "PMID:197601", "title": "beta-Endorphin and adrenocorticotropin are selected concomitantly by the pituitary gland.", "content": "The opiate-like peptide beta-endorphin and adrenocorticotropin are concomitantly secreted in increased amounts by the adenohypophysis in response to acute stress or long-term adrenalectomy as well as in vitro in response to purified corticotropin releasing factor and other secretagogues. Conversely, administration of the synthetic glucocorticoid dexamethasone inhibits the secretion of both adrenocorticotropin and beta-endorphin. Thus, both hormones possess common and identical regulatory mechanisms and there may be a functional role for circulating beta-endorphin.", "contents": "beta-Endorphin and adrenocorticotropin are selected concomitantly by the pituitary gland. The opiate-like peptide beta-endorphin and adrenocorticotropin are concomitantly secreted in increased amounts by the adenohypophysis in response to acute stress or long-term adrenalectomy as well as in vitro in response to purified corticotropin releasing factor and other secretagogues. Conversely, administration of the synthetic glucocorticoid dexamethasone inhibits the secretion of both adrenocorticotropin and beta-endorphin. Thus, both hormones possess common and identical regulatory mechanisms and there may be a functional role for circulating beta-endorphin."}
{"id": "PMID:197602", "title": "Expression of murine sarcoma virus genes in uninfected rat cells subjected to anaerobic sress.", "content": "Exposure of uninfected rat cells in tissue culture to anaerobic culture conditions induces transcription of RNA corresponding to the two principal constituents of rat-derived type-C sarcoma virus genomes: (i) those specific rat cell sequences present in the Kirsten and Harvey murine sarcoma virus genomes, and (ii) an endogenous type-C rat leukemia virus.", "contents": "Expression of murine sarcoma virus genes in uninfected rat cells subjected to anaerobic sress. Exposure of uninfected rat cells in tissue culture to anaerobic culture conditions induces transcription of RNA corresponding to the two principal constituents of rat-derived type-C sarcoma virus genomes: (i) those specific rat cell sequences present in the Kirsten and Harvey murine sarcoma virus genomes, and (ii) an endogenous type-C rat leukemia virus."}
{"id": "PMID:197603", "title": "Synchronized ultradian cortisol rhythms in monkeys: persistence during corticotropin infusion.", "content": "A highly synchronized ultradian cortisol rhythm with a predominant periodicity of 85 to 90 minutes was observed in eight isolated monkeys; this rhythm may be harmonically related to the circadian rhythm. The persistence of this synchronized rhythm during supramaximal infusions of adrenocorticotropin not only suggests that feedback is not causative but also challenges the classic concept that bursts of cortisol secretion are dependent upon an immediately preceding release of adrenocorticotropin.", "contents": "Synchronized ultradian cortisol rhythms in monkeys: persistence during corticotropin infusion. A highly synchronized ultradian cortisol rhythm with a predominant periodicity of 85 to 90 minutes was observed in eight isolated monkeys; this rhythm may be harmonically related to the circadian rhythm. The persistence of this synchronized rhythm during supramaximal infusions of adrenocorticotropin not only suggests that feedback is not causative but also challenges the classic concept that bursts of cortisol secretion are dependent upon an immediately preceding release of adrenocorticotropin."}
{"id": "PMID:197604", "title": "Selective destruction of neurons by a transmitter agonist.", "content": "Microinjection of nanomole amounts of kainic acid, a heterocyclic analog of glutamate, into the cerebellums of adult hamsters and rats causes rapid degeneration of Purkinje, basket, stellate, and Golgi II cells, neurons that receive synaptic input from granule cells, whereas the granule cells themselves are spared. This selectivity is consistent with the evidence that glutamate is the granule cell transmitter and supports the hypothesis that kainic acid exerts its neurotoxic effects through glutamate receptors.", "contents": "Selective destruction of neurons by a transmitter agonist. Microinjection of nanomole amounts of kainic acid, a heterocyclic analog of glutamate, into the cerebellums of adult hamsters and rats causes rapid degeneration of Purkinje, basket, stellate, and Golgi II cells, neurons that receive synaptic input from granule cells, whereas the granule cells themselves are spared. This selectivity is consistent with the evidence that glutamate is the granule cell transmitter and supports the hypothesis that kainic acid exerts its neurotoxic effects through glutamate receptors."}
{"id": "PMID:197606", "title": "[Abnormal hemoglobins in Algeria].", "content": "The existence of frequent hemoglobin abnormalities raises a Public Health problem in Algeria. The presence of genes for hemoglobin S, hemoglobin C and thalassemia in various regions of the country causes severe congenital hemolytic anemias: thalassemia, sickle-cell anemia, S thalassemia, association of HbS and HbC. These diseases are often invaliding requiring frequent admissions to hospital and have a high social cost. We have also observed certain rare hemoglobins, of which some, hemoglobin Setif, hemoglobin D Ouled Rabah were described for the first time in Algerians. They are not pathogenic in the heterozygous state.", "contents": "[Abnormal hemoglobins in Algeria]. The existence of frequent hemoglobin abnormalities raises a Public Health problem in Algeria. The presence of genes for hemoglobin S, hemoglobin C and thalassemia in various regions of the country causes severe congenital hemolytic anemias: thalassemia, sickle-cell anemia, S thalassemia, association of HbS and HbC. These diseases are often invaliding requiring frequent admissions to hospital and have a high social cost. We have also observed certain rare hemoglobins, of which some, hemoglobin Setif, hemoglobin D Ouled Rabah were described for the first time in Algerians. They are not pathogenic in the heterozygous state."}
{"id": "PMID:197607", "title": "[1st cases of alpha-thalassemia in Algeria: 12 cases of hemoglobinosis H].", "content": "These first cases of hemoglobinosis H show that alpha-thalassemia is not a simple curiosity in this part of the Western Mediterranean. They are not localised to a single part of Algeria as the areas from which the patients came were more than 150 km apart. They suggest that the enquiry should be continued by other means to determine the prevalence and pathological incidence.", "contents": "[1st cases of alpha-thalassemia in Algeria: 12 cases of hemoglobinosis H]. These first cases of hemoglobinosis H show that alpha-thalassemia is not a simple curiosity in this part of the Western Mediterranean. They are not localised to a single part of Algeria as the areas from which the patients came were more than 150 km apart. They suggest that the enquiry should be continued by other means to determine the prevalence and pathological incidence."}
{"id": "PMID:197608", "title": "[Clinical and biological aspects of beta-thalassemia. Apropos of 176 cases].", "content": "The study of 176 subjects with beta-thalassemia, associated or not with a hemoglobinopathy, shows great diversity. The hemoglobin C thalassemias are less severe and form a fairly homogeneous group. Sickle cell thalassemia cases have more marked anemia and the disease takes on more varied forms, no doubt because the main mechanism of the anemia, the hyperhemolysis, is influenced by several factors which have a variable effect on the clinical picture. Unassociated thalassemias seem the most polymorphic. Although it seems that in certain foci the beta-thalassemias are fairly stereotyped, this first study shows in Algeria great heterogeneity. All forms are observed both clinically and in the laboratory. Present classifications have not supplied a sufficiently operative model. It is not doubt necessary to await further progress in the laboratory to classify these diseases more precisely.", "contents": "[Clinical and biological aspects of beta-thalassemia. Apropos of 176 cases]. The study of 176 subjects with beta-thalassemia, associated or not with a hemoglobinopathy, shows great diversity. The hemoglobin C thalassemias are less severe and form a fairly homogeneous group. Sickle cell thalassemia cases have more marked anemia and the disease takes on more varied forms, no doubt because the main mechanism of the anemia, the hyperhemolysis, is influenced by several factors which have a variable effect on the clinical picture. Unassociated thalassemias seem the most polymorphic. Although it seems that in certain foci the beta-thalassemias are fairly stereotyped, this first study shows in Algeria great heterogeneity. All forms are observed both clinically and in the laboratory. Present classifications have not supplied a sufficiently operative model. It is not doubt necessary to await further progress in the laboratory to classify these diseases more precisely."}
{"id": "PMID:197609", "title": "[Glucose-6-phosphate dehydrogenase deficiency in Algeria].", "content": "The normal level of G6PD activity of the red cells is 6.6 +/- 1.6 i.u/g Hb in men and 6.9 +/- 1.6 i.u./g Hb in women. The histogram of the distribution in the population is not symmetrical. G6PD deficiency is present in Algeria at the national level of 3% (+/- 0.5). The level is less high in the mountainous areas of arab culture, higher in the berber culture and in the Shara. Numerous new variants have been detected in Algeria. The G6PD deficiency predominating in Algeria is of Kabyle type, followed by Laghouat and El-Qued types. Types A-, A+ and Ibaden Austin of negro origin exist in the Sahara population. The Mediterranean type is not found in the Algerian population. The clinical manifestations are rare.", "contents": "[Glucose-6-phosphate dehydrogenase deficiency in Algeria]. The normal level of G6PD activity of the red cells is 6.6 +/- 1.6 i.u/g Hb in men and 6.9 +/- 1.6 i.u./g Hb in women. The histogram of the distribution in the population is not symmetrical. G6PD deficiency is present in Algeria at the national level of 3% (+/- 0.5). The level is less high in the mountainous areas of arab culture, higher in the berber culture and in the Shara. Numerous new variants have been detected in Algeria. The G6PD deficiency predominating in Algeria is of Kabyle type, followed by Laghouat and El-Qued types. Types A-, A+ and Ibaden Austin of negro origin exist in the Sahara population. The Mediterranean type is not found in the Algerian population. The clinical manifestations are rare."}
{"id": "PMID:197610", "title": "[Hemolytic anemia caused by glucose-6-phosphate dehydrogenase deficiency. Aprpos of 20 cases from 1969 to 1974].", "content": "Twenty hemolytic accidents due to G6PD deficiency in Algeria are reported: 13 cases of favism, 2 cases of neonatal jaundice, one drug accident (aspirin), 4 of unknown cause. These accidents concern above all children, were clinically severe and required transfusion.", "contents": "[Hemolytic anemia caused by glucose-6-phosphate dehydrogenase deficiency. Aprpos of 20 cases from 1969 to 1974]. Twenty hemolytic accidents due to G6PD deficiency in Algeria are reported: 13 cases of favism, 2 cases of neonatal jaundice, one drug accident (aspirin), 4 of unknown cause. These accidents concern above all children, were clinically severe and required transfusion."}
{"id": "PMID:197611", "title": "[Pi W3 Constantine, new allele of Pi system].", "content": "The authors describe a new allele Pi W3 Constantine, present in the Algerian population. This allele was not responsible for pathological manifestations.", "contents": "[Pi W3 Constantine, new allele of Pi system]. The authors describe a new allele Pi W3 Constantine, present in the Algerian population. This allele was not responsible for pathological manifestations."}
{"id": "PMID:197612", "title": "[Comparison between acute myeloblastic leukemia in children and adults].", "content": "The clinical, hematological and therapeutic aspects of 36 cases of acute myeloblastic leukemia in children and 98 cases in adults observed in Algeria are discussed. In Algeria, acute myeloblastic leukemia is more frequent in children than in other populations. In our series there was a very unusual female predominance. Clinically, we observed in children only, 8 cases of chloroma of the orbit. From the hematological point of view, the only difference was a higher incidence of leukopenia and hyperleukocytosis after the age 30 years. The results of VAMP treatment (vincristin, amethopterin, 6-mercaptopurine, and prednisone) are better in children than in adults. But analysis of the results is more interesting if one places the patients in age groups of ten years. The percentage of complete remissions is maximum in the age group 0 to 10years and then falls regularly.", "contents": "[Comparison between acute myeloblastic leukemia in children and adults]. The clinical, hematological and therapeutic aspects of 36 cases of acute myeloblastic leukemia in children and 98 cases in adults observed in Algeria are discussed. In Algeria, acute myeloblastic leukemia is more frequent in children than in other populations. In our series there was a very unusual female predominance. Clinically, we observed in children only, 8 cases of chloroma of the orbit. From the hematological point of view, the only difference was a higher incidence of leukopenia and hyperleukocytosis after the age 30 years. The results of VAMP treatment (vincristin, amethopterin, 6-mercaptopurine, and prednisone) are better in children than in adults. But analysis of the results is more interesting if one places the patients in age groups of ten years. The percentage of complete remissions is maximum in the age group 0 to 10years and then falls regularly."}
{"id": "PMID:197613", "title": "[Familial leukemia].", "content": "Two cases of acute myeloblastic leukemia were observed in a young 22 year old woman, then two years later, in her brother aged 16 years. The elder brother had died previously probably from the same disease. The very rare families in which more than two members had the same type of leukemia show the possible intervention of a hereditary factor in leukemogenesis.", "contents": "[Familial leukemia]. Two cases of acute myeloblastic leukemia were observed in a young 22 year old woman, then two years later, in her brother aged 16 years. The elder brother had died previously probably from the same disease. The very rare families in which more than two members had the same type of leukemia show the possible intervention of a hereditary factor in leukemogenesis."}
{"id": "PMID:197616", "title": "[Electrophysiologic abnormalities in chronic alcoholism, disclosed by the methods of evoked potentials and Hoffman's reflex. Study of a possible metabolic pathogenesis].", "content": "During a preliminary study comparing 5 normal subjects and 5 alcoholics (25 experiments) changes in evoked potentials were found in these patients. There was mainly a reduction in these potentials during the first 100 milleseconds following stimulation. Such a reduction generally means a disorder of the arrival of the influx at the level of the cortex and may be found mainly in peripheral nerve involvement. A complementary study of the H reflex (34 experiments) showed that this reflex was affected in 60% of chronic alcoholics whether or not they had liver cirrhosis. The theory according to which the EEG abnormalities observed may be linked to a metabolic disorder of the amino-acids was not confirmed. The changes of the first 100 milleseconds of the evoked potential associated with the change in Hoffman's reflex are in favour of early peripheral involvement even in alcoholics who do not appear to have any peripheral neuritis. These signs are different from those which are observed in marijuana or psylocybine poisoning where the EEG signs are due to central involvement.", "contents": "[Electrophysiologic abnormalities in chronic alcoholism, disclosed by the methods of evoked potentials and Hoffman's reflex. Study of a possible metabolic pathogenesis]. During a preliminary study comparing 5 normal subjects and 5 alcoholics (25 experiments) changes in evoked potentials were found in these patients. There was mainly a reduction in these potentials during the first 100 milleseconds following stimulation. Such a reduction generally means a disorder of the arrival of the influx at the level of the cortex and may be found mainly in peripheral nerve involvement. A complementary study of the H reflex (34 experiments) showed that this reflex was affected in 60% of chronic alcoholics whether or not they had liver cirrhosis. The theory according to which the EEG abnormalities observed may be linked to a metabolic disorder of the amino-acids was not confirmed. The changes of the first 100 milleseconds of the evoked potential associated with the change in Hoffman's reflex are in favour of early peripheral involvement even in alcoholics who do not appear to have any peripheral neuritis. These signs are different from those which are observed in marijuana or psylocybine poisoning where the EEG signs are due to central involvement."}
{"id": "PMID:197617", "title": "[2000 chronic carriers of HBs antigen].", "content": "By a study of 2000 asymptomatic carriers of the HBs antigen, the following information was obtained: their frequency is 3 times greater in men than in women and twice as great in young subjects as compared with subjects aged over 35 years. However an increase in this frequency is noted beyond 55 years. The titre of the HBs antigen is not related to age, except for low titres, (5.65% of carriers frequent beyond the age of 45 years. The ratio an/ay (major subtypes) is 2.6 in French subjects. It does not vary with age. It is 1.6 in subjects of Group 0. Normal liver function tests were observed in 78.5% of all carriers, (women 91.5%, men 73.4%) and in only 45.6% of those with a high HBs antigen titre.", "contents": "[2000 chronic carriers of HBs antigen]. By a study of 2000 asymptomatic carriers of the HBs antigen, the following information was obtained: their frequency is 3 times greater in men than in women and twice as great in young subjects as compared with subjects aged over 35 years. However an increase in this frequency is noted beyond 55 years. The titre of the HBs antigen is not related to age, except for low titres, (5.65% of carriers frequent beyond the age of 45 years. The ratio an/ay (major subtypes) is 2.6 in French subjects. It does not vary with age. It is 1.6 in subjects of Group 0. Normal liver function tests were observed in 78.5% of all carriers, (women 91.5%, men 73.4%) and in only 45.6% of those with a high HBs antigen titre."}
{"id": "PMID:197619", "title": "[Kahler's disease. Elements of a rheumatologic series].", "content": "The authors report the main data of a series collected on a rheumatology unit where the bony signs were most obvious. Survival was comparable with that of large series in the literature. The prognosis seems to be linked to numerous factors therapeutic and etiologic (age, sex, type of monoclonal immunoglobulin) visceral and blood involvement. The diagnosis is now made earlier, but the differential diagnosis includes the other monoclonal immunoglobulin gammapathies.", "contents": "[Kahler's disease. Elements of a rheumatologic series]. The authors report the main data of a series collected on a rheumatology unit where the bony signs were most obvious. Survival was comparable with that of large series in the literature. The prognosis seems to be linked to numerous factors therapeutic and etiologic (age, sex, type of monoclonal immunoglobulin) visceral and blood involvement. The diagnosis is now made earlier, but the differential diagnosis includes the other monoclonal immunoglobulin gammapathies."}
{"id": "PMID:197621", "title": "[Parasitic rheumatism].", "content": "The joint manifestations of parasitic diseases are rare. They may be due to the presence of a parasite within one or severed joints, to involvement of a neighbouring joint, or distant involvement due to an immuno-allergic mechanism. The latter category constitutes what one may call parasitic rheumatism. The latter is characterised by arthropathies of inflammatory type with raised sedimentation rate, marked but inconstant hypereosinophilia, and total inefficacy of antirheumatic treatments. The diagnosis of parasitic rheumatism depends on these criteria, on the diagnosis of the parasitic disease in question, above all filariasis but also other parasitic diseases, and above all the great efficacy of specific anti-parasitic treatments.", "contents": "[Parasitic rheumatism]. The joint manifestations of parasitic diseases are rare. They may be due to the presence of a parasite within one or severed joints, to involvement of a neighbouring joint, or distant involvement due to an immuno-allergic mechanism. The latter category constitutes what one may call parasitic rheumatism. The latter is characterised by arthropathies of inflammatory type with raised sedimentation rate, marked but inconstant hypereosinophilia, and total inefficacy of antirheumatic treatments. The diagnosis of parasitic rheumatism depends on these criteria, on the diagnosis of the parasitic disease in question, above all filariasis but also other parasitic diseases, and above all the great efficacy of specific anti-parasitic treatments."}
{"id": "PMID:197627", "title": "[Recent acquisitions concerning mediatinopulmonary sarcoidosis].", "content": "Sarcoidosis is a disease defined by two criteria: one quantitative involvement if several organs or tissues showing its systemic character) the other qualitative (presence in all affected organs of giant cell and epitheloid cell granulomas without caseation). The first seems to counter balance the absence of specificity of the second. Unfortunately, the quantitative factor may be lacking in the mediastino-pulmonary forms owing to their apparently localised character. The diagnosis is thus based on a critical study of the clinical context (age, general health radiological appearances) and indirect signs of diffusion (biopsies, immune reactions, Kweim test). The therapeutic indications should take into consideration the tendancy to spontaneous recovery which occurs in 98% of cases. Prolonged corticosteroid therapy may be difficult to stop. No treatment should therefore be given unless there are complications or associated lesions exposing the patient to the risk of severe and permanent sequelae.", "contents": "[Recent acquisitions concerning mediatinopulmonary sarcoidosis]. Sarcoidosis is a disease defined by two criteria: one quantitative involvement if several organs or tissues showing its systemic character) the other qualitative (presence in all affected organs of giant cell and epitheloid cell granulomas without caseation). The first seems to counter balance the absence of specificity of the second. Unfortunately, the quantitative factor may be lacking in the mediastino-pulmonary forms owing to their apparently localised character. The diagnosis is thus based on a critical study of the clinical context (age, general health radiological appearances) and indirect signs of diffusion (biopsies, immune reactions, Kweim test). The therapeutic indications should take into consideration the tendancy to spontaneous recovery which occurs in 98% of cases. Prolonged corticosteroid therapy may be difficult to stop. No treatment should therefore be given unless there are complications or associated lesions exposing the patient to the risk of severe and permanent sequelae."}
{"id": "PMID:197628", "title": "[Treatment of hypercalcemia].", "content": "Hypercalcemia may have various causes. I should nevertheless be rapidly treated. Among recent treatmens, we may quote diuresis with furosemide, calcitonin, mithramycin, which are the most effective. More recently indomethacin has been used and may be more specific for neoplastic hypercalcemia. These various treatments should be proposed depending on the level of serum calcium, the rapidity of onset and the presumed cause.", "contents": "[Treatment of hypercalcemia]. Hypercalcemia may have various causes. I should nevertheless be rapidly treated. Among recent treatmens, we may quote diuresis with furosemide, calcitonin, mithramycin, which are the most effective. More recently indomethacin has been used and may be more specific for neoplastic hypercalcemia. These various treatments should be proposed depending on the level of serum calcium, the rapidity of onset and the presumed cause."}
{"id": "PMID:197620", "title": "[Lymphatoid papulosis. Ultrastructural study. Review of the literature].", "content": "The authors report a case of lymphomatoid papulosis with an ultrastructural study, and review 84 cases which they found in the literature. They recall the clinical and histological signs and the course of this disease which usually has a benign prognosis. The classification and relationship with varioliform parapsoriasis of Mucha-Habermann and the hematodermias remain debated.", "contents": "[Lymphatoid papulosis. Ultrastructural study. Review of the literature]. The authors report a case of lymphomatoid papulosis with an ultrastructural study, and review 84 cases which they found in the literature. They recall the clinical and histological signs and the course of this disease which usually has a benign prognosis. The classification and relationship with varioliform parapsoriasis of Mucha-Habermann and the hematodermias remain debated."}
{"id": "PMID:197629", "title": "[Iatrogenic thyroid pathology].", "content": "A physiological dose of iodine is necessary for thyroid hormonogenesis, but in pharmacological dosage it is a danger. Massive intakes of iodine, always of medical origin (radiodiagnosis, therapeutic) trigger off a defence mechanism in the thyroid gland, called Wolff-Chaikoff effect. This useful mechanism may be defective and abnormalities of thyroid function may appear either in the form of hypothyroidsm with goitre or temporary hyperthyroidism. The increasing use of drugs containg iodine and certain specially noxious substances such as amiodarone in particular give this iatrogenic thyroid pathology a new dimension, for it is no longer seen only by the specialist but also by the general practitioner. It involves the doctor's reponsibility not only in diagnosis but also in treatment.", "contents": "[Iatrogenic thyroid pathology]. A physiological dose of iodine is necessary for thyroid hormonogenesis, but in pharmacological dosage it is a danger. Massive intakes of iodine, always of medical origin (radiodiagnosis, therapeutic) trigger off a defence mechanism in the thyroid gland, called Wolff-Chaikoff effect. This useful mechanism may be defective and abnormalities of thyroid function may appear either in the form of hypothyroidsm with goitre or temporary hyperthyroidism. The increasing use of drugs containg iodine and certain specially noxious substances such as amiodarone in particular give this iatrogenic thyroid pathology a new dimension, for it is no longer seen only by the specialist but also by the general practitioner. It involves the doctor's reponsibility not only in diagnosis but also in treatment."}
{"id": "PMID:197630", "title": "[Surveillance of hypothyroidism treatment].", "content": "The efficacy of substitution treatment in primary or secondary hypothyroidism is based on the diappearance of the clinical signs of the disease and the return of blood levels of thyroxine and TSH within normal limits. The dosage should be adapted to the age of the patient the duration of the course of the hypothyroidism and the state of the heart. The cardio-vascular consequences of hypothroidism are so serious that one should know how to detect them straight away, and thus prevent complications with would prevent proper substitutive treatment.", "contents": "[Surveillance of hypothyroidism treatment]. The efficacy of substitution treatment in primary or secondary hypothyroidism is based on the diappearance of the clinical signs of the disease and the return of blood levels of thyroxine and TSH within normal limits. The dosage should be adapted to the age of the patient the duration of the course of the hypothyroidism and the state of the heart. The cardio-vascular consequences of hypothroidism are so serious that one should know how to detect them straight away, and thus prevent complications with would prevent proper substitutive treatment."}
{"id": "PMID:197631", "title": "[New data in the domain of insulin resistance].", "content": "Insulin resistance may occur to a variable degree in various disease conditions. Obesity is frequently accompanied by insulin resistance. The anti-insulin antibodies in patients treated with insulin are a classical cause, but in fact rare. Insulin resistance of variable degree may accompany certain metabolic disorders, e.g. diabetic ketosis and acidosis, and endocrine disorders, e.g. Cushing's syndrome, acromegaly. The measurement of insulin receptors brings a new dimension to the investigation of insulin resistance. Insulin receptors are reduced in number during obesity. The abnormality, partly responsible for insulin resistance, is reducible by reduction in calory intake. Circulating insulin anti-receptor antibodies appear to be responsible for insulin resistance which is particularly marked although exeptional, in nonobese diabetics with acanthosis nigrans and auto-immune symptoms.", "contents": "[New data in the domain of insulin resistance]. Insulin resistance may occur to a variable degree in various disease conditions. Obesity is frequently accompanied by insulin resistance. The anti-insulin antibodies in patients treated with insulin are a classical cause, but in fact rare. Insulin resistance of variable degree may accompany certain metabolic disorders, e.g. diabetic ketosis and acidosis, and endocrine disorders, e.g. Cushing's syndrome, acromegaly. The measurement of insulin receptors brings a new dimension to the investigation of insulin resistance. Insulin receptors are reduced in number during obesity. The abnormality, partly responsible for insulin resistance, is reducible by reduction in calory intake. Circulating insulin anti-receptor antibodies appear to be responsible for insulin resistance which is particularly marked although exeptional, in nonobese diabetics with acanthosis nigrans and auto-immune symptoms."}
{"id": "PMID:197632", "title": "[Angio-immunoblastic lymphadenopathy with dysproteinemia. Apropos of 5 cases].", "content": "Angio-immunoblastic lymphadenopathies with dysproteinemia represent a new entity characterised clinically by superficial lymphadenopathy splenomegaly more frequent than hepatomegaly, marked general signs and skin manifestations often triggered off by drugs. The laboratory disturbances include immue disorders, polyclonal dysproteinemia, anti-red cell autoimmunity. It is above all the histology which makes this entity original: polymorphic cellular proliferation with immunoblasts, plasmablasts and plasma cell disturbing the normal lymph node architecutre, intense vascular neogenesis and deposits of extra-cellular amorphous substances. This histology corresponds to a non-sarcomatous lymph node hyperplasia, probably due to a deficit in T suppressive function on the production of antibodies.", "contents": "[Angio-immunoblastic lymphadenopathy with dysproteinemia. Apropos of 5 cases]. Angio-immunoblastic lymphadenopathies with dysproteinemia represent a new entity characterised clinically by superficial lymphadenopathy splenomegaly more frequent than hepatomegaly, marked general signs and skin manifestations often triggered off by drugs. The laboratory disturbances include immue disorders, polyclonal dysproteinemia, anti-red cell autoimmunity. It is above all the histology which makes this entity original: polymorphic cellular proliferation with immunoblasts, plasmablasts and plasma cell disturbing the normal lymph node architecutre, intense vascular neogenesis and deposits of extra-cellular amorphous substances. This histology corresponds to a non-sarcomatous lymph node hyperplasia, probably due to a deficit in T suppressive function on the production of antibodies."}
{"id": "PMID:197633", "title": "[Hyperprolactinism and antiprolactin drugs].", "content": "After being suspected in the presence of galactorrhoea, it is now easy to prove hyperprolactinism thanks to radioimmunoassay of prolactin. The repercussions of hyperprolactinism on gonad function are now well known, especially in women where they lead to anovulation then amenorrhoea, whereas in man there occurs hypoandrogenism with loss of libido. Hyperprolactinemia may occur in numerous circumstances and may be deduced logically from the mechanism of secretory regulation of this hormone. Among the latter, one cause dominates the others by its therapeutic consequences, I.e. the presence of an adenoma or microadenoma secreting prolactin discovered thanks to tomography of the sella turcica. The treatment of hyperprolactinism has advanced in recent years with the introduction of dopamineric drugs such as bromcriptin which permits one to normalise prolactinemia and thus restore gonad function. It's use requires however certain precautions and neurological and ophthalmic supervision when htere is a microadenoma.", "contents": "[Hyperprolactinism and antiprolactin drugs]. After being suspected in the presence of galactorrhoea, it is now easy to prove hyperprolactinism thanks to radioimmunoassay of prolactin. The repercussions of hyperprolactinism on gonad function are now well known, especially in women where they lead to anovulation then amenorrhoea, whereas in man there occurs hypoandrogenism with loss of libido. Hyperprolactinemia may occur in numerous circumstances and may be deduced logically from the mechanism of secretory regulation of this hormone. Among the latter, one cause dominates the others by its therapeutic consequences, I.e. the presence of an adenoma or microadenoma secreting prolactin discovered thanks to tomography of the sella turcica. The treatment of hyperprolactinism has advanced in recent years with the introduction of dopamineric drugs such as bromcriptin which permits one to normalise prolactinemia and thus restore gonad function. It's use requires however certain precautions and neurological and ophthalmic supervision when htere is a microadenoma."}
{"id": "PMID:197634", "title": "[Various aspects of cytomegalovirus infection in the adult].", "content": "Cytomegalovirus infection was sought as a routine over a period of two year in 100 patients of which 34 had a suitable constitutional background [corrected] for this type infection (multiple transfusions, malignant disease, immunodepression). The authors attempt to circumscibe the main clinical aspects encountered in adults. They consider the repective diagnostic values of isolation of the virus and serological reactions. They discuss their interpretation during the course of an infection.", "contents": "[Various aspects of cytomegalovirus infection in the adult]. Cytomegalovirus infection was sought as a routine over a period of two year in 100 patients of which 34 had a suitable constitutional background [corrected] for this type infection (multiple transfusions, malignant disease, immunodepression). The authors attempt to circumscibe the main clinical aspects encountered in adults. They consider the repective diagnostic values of isolation of the virus and serological reactions. They discuss their interpretation during the course of an infection."}
{"id": "PMID:197635", "title": "[Diagnosis of incomplete hypothyroidism].", "content": "The clinical picture of mild hypothyroidism consists of mild, often non-specific signs. In general, the diagnosis can only be made in the laboratory. Estimations of protein-bound iodine, thyroxine and tri-iodothyronine in the serum are often within normal limits. A rise in serum TSH and in doubtful cases, the excessive liberation of TSH during the TRH-TSH test confirm the diagnosis. As mild hypothyroidism is often due to auto-immune thyroiditis, the demonstration of anti-thyroid antibodies may guide the clinician.", "contents": "[Diagnosis of incomplete hypothyroidism]. The clinical picture of mild hypothyroidism consists of mild, often non-specific signs. In general, the diagnosis can only be made in the laboratory. Estimations of protein-bound iodine, thyroxine and tri-iodothyronine in the serum are often within normal limits. A rise in serum TSH and in doubtful cases, the excessive liberation of TSH during the TRH-TSH test confirm the diagnosis. As mild hypothyroidism is often due to auto-immune thyroiditis, the demonstration of anti-thyroid antibodies may guide the clinician."}
{"id": "PMID:197636", "title": "[Hepatic and pancreatic tomometry. Radioanatomy and application to hepatic pathology].", "content": "More than 250 hepatic and pancreatic tomometries were carried out on a first generation tomometer. Anatomical and tomometric correspondances carried out on the cadaver led to precise radiological anatomy of the abdomen. Tomometry either alone or carried out after impregnation of the liver parenchyma with an emusion of lipiodol in low dosage permits one to demonstrate hepatic lesions of the order of one centimeter diameter whatever their localisation. Densitometry differentiates not only solid lesions from fluid lesions but permits in certain cases a diagnosis of the nature of the lesion.", "contents": "[Hepatic and pancreatic tomometry. Radioanatomy and application to hepatic pathology]. More than 250 hepatic and pancreatic tomometries were carried out on a first generation tomometer. Anatomical and tomometric correspondances carried out on the cadaver led to precise radiological anatomy of the abdomen. Tomometry either alone or carried out after impregnation of the liver parenchyma with an emusion of lipiodol in low dosage permits one to demonstrate hepatic lesions of the order of one centimeter diameter whatever their localisation. Densitometry differentiates not only solid lesions from fluid lesions but permits in certain cases a diagnosis of the nature of the lesion."}
{"id": "PMID:197637", "title": "[Impact of immune disorders in digestive pathology].", "content": "The digestive tract has a special immune system where predominate the secretory factors of IgA. The IgA secreted by the plasma cells of the digestive mucosa is dimeric and is  poured into the intestinal lumen after being attached to a protein of epithelial orgin. These facts lead to defence reactions of a special type. The digestive consequences of a quantitative abnormality of this system (hypogammaglobulinemia) or qualitative abnormality such as alpha heavy chain disease or Whipple's disease, are briefly reviewed. The consequences of an abnormal response of this system are considered in the light of present knowledge concerning coeliac disease. On the whole, these recent studies should lead to a revision of the idea of digestive allergy.", "contents": "[Impact of immune disorders in digestive pathology]. The digestive tract has a special immune system where predominate the secretory factors of IgA. The IgA secreted by the plasma cells of the digestive mucosa is dimeric and is  poured into the intestinal lumen after being attached to a protein of epithelial orgin. These facts lead to defence reactions of a special type. The digestive consequences of a quantitative abnormality of this system (hypogammaglobulinemia) or qualitative abnormality such as alpha heavy chain disease or Whipple's disease, are briefly reviewed. The consequences of an abnormal response of this system are considered in the light of present knowledge concerning coeliac disease. On the whole, these recent studies should lead to a revision of the idea of digestive allergy."}
{"id": "PMID:197638", "title": "[Problem posed by the prevention and detection of colorectal cancers].", "content": "The incidence of colonic and rectal carcinoma is in constant progression. The detection and destruction of polyps is the only effective means of reducing the number of adenocarcinomas. The technical means of detection are well known and fully proved: rectosigmoidoscopy, thin layer double contrast enema, colonoscopy. The true problem is that of the cost of this prevention. It is important to define high risk groups in which these tests should be carried out as a routine. Furthermore it is necessary to know whether blood tests or examination of the stools may be considered as a means of detection of polyp or at least certain types of potentially malignant polyp. without suggesting a considerable increase in the number of medical investigations, one may hope for better use of sigmoidoscopy and double contrast barium enema. These two examinations represent undoubtedly the essential factor in the diagnosis of colonic and rectal tumours.", "contents": "[Problem posed by the prevention and detection of colorectal cancers]. The incidence of colonic and rectal carcinoma is in constant progression. The detection and destruction of polyps is the only effective means of reducing the number of adenocarcinomas. The technical means of detection are well known and fully proved: rectosigmoidoscopy, thin layer double contrast enema, colonoscopy. The true problem is that of the cost of this prevention. It is important to define high risk groups in which these tests should be carried out as a routine. Furthermore it is necessary to know whether blood tests or examination of the stools may be considered as a means of detection of polyp or at least certain types of potentially malignant polyp. without suggesting a considerable increase in the number of medical investigations, one may hope for better use of sigmoidoscopy and double contrast barium enema. These two examinations represent undoubtedly the essential factor in the diagnosis of colonic and rectal tumours."}
{"id": "PMID:197639", "title": "[Physiopathologic mechanism of water-electrolyte diarrhea].", "content": "The physiopathological mechanism of diarrhea with water and electrolyte disturbances is not fully clear. But it already appears that progress in our knowledge of the pathology goes together with progress in physiology. Work on cholera has clarified our knowledge of intestinal were not fully realised. In the short term one may foresee that our concept of the regulation of digestion of a meal will change.", "contents": "[Physiopathologic mechanism of water-electrolyte diarrhea]. The physiopathological mechanism of diarrhea with water and electrolyte disturbances is not fully clear. But it already appears that progress in our knowledge of the pathology goes together with progress in physiology. Work on cholera has clarified our knowledge of intestinal were not fully realised. In the short term one may foresee that our concept of the regulation of digestion of a meal will change."}
{"id": "PMID:197640", "title": "[Medical treatment and Cushing's disease].", "content": "The drugs proposed are considered according to their site of action. Synthetic anti-cortisol drugs (Op'DDD in particular and aminoglutethimide) appear to be the drugs of choice at present. They act on the adrenals, but research is now being carried out on drugs which act on ACTH secretion, E.g; cyproheptadine and bromocriptine.", "contents": "[Medical treatment and Cushing's disease]. The drugs proposed are considered according to their site of action. Synthetic anti-cortisol drugs (Op'DDD in particular and aminoglutethimide) appear to be the drugs of choice at present. They act on the adrenals, but research is now being carried out on drugs which act on ACTH secretion, E.g; cyproheptadine and bromocriptine."}
{"id": "PMID:197641", "title": "[Current concept of the mechanism of proteinuria].", "content": "Plasma proteins cross the glomerular basement membrane in inverse proportion to their molecular dimension; molecules larger than serum albumin are completely excluded from the glomerular filtrate. This filtration, which is purely passive, also depends of the electrical charge of the proteins; negatively charged proteins are indeed repelled by the negatively charged layer of sialogylcoproteins present along the outer surface of the epithelial cell membrane and extending to the glomerular basement membrane. The filtered proteins are selectively absorbed by the proximal tubular cells and are hydrolyzed by lysosomal enzymes. This results in a renal catabolism of proteins the importance of which depends on their ability to cross the glomerular barrier. In renal disease, proteinuria results either from an increased permeability of the glomerular basement membrane (selective or non-selective glomerular proteinuria) or from a diminished tubular reabsorption of normally filtered proteins of low molecular weight (tubular proteinuria).", "contents": "[Current concept of the mechanism of proteinuria]. Plasma proteins cross the glomerular basement membrane in inverse proportion to their molecular dimension; molecules larger than serum albumin are completely excluded from the glomerular filtrate. This filtration, which is purely passive, also depends of the electrical charge of the proteins; negatively charged proteins are indeed repelled by the negatively charged layer of sialogylcoproteins present along the outer surface of the epithelial cell membrane and extending to the glomerular basement membrane. The filtered proteins are selectively absorbed by the proximal tubular cells and are hydrolyzed by lysosomal enzymes. This results in a renal catabolism of proteins the importance of which depends on their ability to cross the glomerular barrier. In renal disease, proteinuria results either from an increased permeability of the glomerular basement membrane (selective or non-selective glomerular proteinuria) or from a diminished tubular reabsorption of normally filtered proteins of low molecular weight (tubular proteinuria)."}
{"id": "PMID:197643", "title": "[\"Vitamin resistant\" osteomalacia due to a defect in hepatic hydroxylation of vitamin D; reversible secondary-pseudo-hypoparathyroidism due to calcium administration].", "content": "The authors report a case of vitamin resistant osteomalacia in an adult due to an apparently acquired absence of hepatic hydroxylation of vitamin D. This case was also of interest as the osteomalacia caused a state of type II pseudo-hypoparathyroidism which proved reversible on calcium drip. Thus a defect of hepatic hydroxylation of vitamin D may be a cause of vitamin resistant osteomalacia in the adult apart from the forms already described related to defect of renal hydroxylation of vitamin D. Hypocalcemia may be responsible for hypoparathyroidism due to the coexistence of a rise of circulating immuno-reactive PTH and an increase in urinary cyclic AMP. Normalisation of the calcemia permitted in this case, restoral of the efficacy of endogenous PTH.", "contents": "[\"Vitamin resistant\" osteomalacia due to a defect in hepatic hydroxylation of vitamin D; reversible secondary-pseudo-hypoparathyroidism due to calcium administration]. The authors report a case of vitamin resistant osteomalacia in an adult due to an apparently acquired absence of hepatic hydroxylation of vitamin D. This case was also of interest as the osteomalacia caused a state of type II pseudo-hypoparathyroidism which proved reversible on calcium drip. Thus a defect of hepatic hydroxylation of vitamin D may be a cause of vitamin resistant osteomalacia in the adult apart from the forms already described related to defect of renal hydroxylation of vitamin D. Hypocalcemia may be responsible for hypoparathyroidism due to the coexistence of a rise of circulating immuno-reactive PTH and an increase in urinary cyclic AMP. Normalisation of the calcemia permitted in this case, restoral of the efficacy of endogenous PTH."}
{"id": "PMID:197644", "title": "[Role of folic-acid deficiency in deficiency diseases of the nervous system. Apropos of 12 cases including an anatomo-clinical case].", "content": "The authors report 12 cases of neurological syndromes due to folic acid deficiency, due in 8 cases to chronic alcoholism. In 5 cases there was polyneuritis, 3 cases had cerebellar atrophy, whilst 4 patients had subacute combined degeneration of the cord. Folic acid deficiency occurred alone in five cases out of twelve, as in 3 cases vitamin B1 deficiency was associated, and in four cases there was malabsorption of vitamin B12. A neuropathological study of these cases showed: 1) moderate involvement of the mamillary tubercles as observed in deficiency encephalopathies. 2) severe peripheral nerve involvement especially of axonal type. 3) involvement of the anterior horns of the spinal cord with appearances of central chromatolysis and a few atrophic neurones.", "contents": "[Role of folic-acid deficiency in deficiency diseases of the nervous system. Apropos of 12 cases including an anatomo-clinical case]. The authors report 12 cases of neurological syndromes due to folic acid deficiency, due in 8 cases to chronic alcoholism. In 5 cases there was polyneuritis, 3 cases had cerebellar atrophy, whilst 4 patients had subacute combined degeneration of the cord. Folic acid deficiency occurred alone in five cases out of twelve, as in 3 cases vitamin B1 deficiency was associated, and in four cases there was malabsorption of vitamin B12. A neuropathological study of these cases showed: 1) moderate involvement of the mamillary tubercles as observed in deficiency encephalopathies. 2) severe peripheral nerve involvement especially of axonal type. 3) involvement of the anterior horns of the spinal cord with appearances of central chromatolysis and a few atrophic neurones."}
{"id": "PMID:197642", "title": "[Cytological diagnosis of bronchial cancers from samples obtained through broncho-fibroscopy].", "content": "The results of cytological studies of samples obtained by fibre endoscopy of the bronchus in 160 cases of bronchial ; carcinoma were analysed. Thanks to the routine use of brushing, aspiration, often selective and sputum examination, the diagnosis was obtained in 62% of cases. Naturally it was mainly positive in the proximal budding forms (78%) but the figures in the distal forms, including those where fibre endoscopy was negative, remained high (54%). There was never a true false positive, and the cytohistological correlation was almost 100%. Distal aspirations were the most useful in peripheral forms, whilst brushing was more useful in proximal forms. In any case thanks to these new technics, fibre endoscopy has become a simple examination for routine use which has now a very important place in the diagnosis of bronchial carcinoma.", "contents": "[Cytological diagnosis of bronchial cancers from samples obtained through broncho-fibroscopy]. The results of cytological studies of samples obtained by fibre endoscopy of the bronchus in 160 cases of bronchial ; carcinoma were analysed. Thanks to the routine use of brushing, aspiration, often selective and sputum examination, the diagnosis was obtained in 62% of cases. Naturally it was mainly positive in the proximal budding forms (78%) but the figures in the distal forms, including those where fibre endoscopy was negative, remained high (54%). There was never a true false positive, and the cytohistological correlation was almost 100%. Distal aspirations were the most useful in peripheral forms, whilst brushing was more useful in proximal forms. In any case thanks to these new technics, fibre endoscopy has become a simple examination for routine use which has now a very important place in the diagnosis of bronchial carcinoma."}
{"id": "PMID:197648", "title": "Radioactive sodium selenite in the differentiation of hepatic lesions.", "content": "Selenium-75 selenite and technetium-99m sulphur colloid scans were performed on 38 South African Blacks with intrahepatic space-occupying lesions. Uptake of selenite was demonstrated in the 'cold area' on the sulphur colloid scan in 17 out of 19 patients with hepatocellular carcinoma, but in 16 patients with amoebic liver abscess there was no uptake of selenite in the 'cold area'. In 3 patients with secondary involvement in the liver, 2 had positive uptake of selenite in the affected region. 75Se selenite was found to be useful in the differential diagnosis of intrahepatic lesions.", "contents": "Radioactive sodium selenite in the differentiation of hepatic lesions. Selenium-75 selenite and technetium-99m sulphur colloid scans were performed on 38 South African Blacks with intrahepatic space-occupying lesions. Uptake of selenite was demonstrated in the 'cold area' on the sulphur colloid scan in 17 out of 19 patients with hepatocellular carcinoma, but in 16 patients with amoebic liver abscess there was no uptake of selenite in the 'cold area'. In 3 patients with secondary involvement in the liver, 2 had positive uptake of selenite in the affected region. 75Se selenite was found to be useful in the differential diagnosis of intrahepatic lesions."}
{"id": "PMID:197650", "title": "Hepatoportal arteriovenous fistula in primary carcinoma of the liver.", "content": "The correlation between the portal circulation and esophageal varices was evaluated in 80 patients with a primary carcinoma of the liver, with special regard being given to the significance of an hepatoportal arteriovenous fistula. Hepatoportal arteriovenous fistula was found in eight patients. Esophageal varices were observed 32 of all patients with a hepatoma. On the other hand, variceal lesions were found in 17 of 52 patients without compared with all patients with an hepatoportal arteriovenous fistula. A fatal hemorrhage was frequently encountered in the patients with the fistula. It was suggested that a rational treatment for those with the triple lesions--hepatoma, esophageal varices and hepatoportal arteriovenous fistula--may be ligation of the hepatic artery.", "contents": "Hepatoportal arteriovenous fistula in primary carcinoma of the liver. The correlation between the portal circulation and esophageal varices was evaluated in 80 patients with a primary carcinoma of the liver, with special regard being given to the significance of an hepatoportal arteriovenous fistula. Hepatoportal arteriovenous fistula was found in eight patients. Esophageal varices were observed 32 of all patients with a hepatoma. On the other hand, variceal lesions were found in 17 of 52 patients without compared with all patients with an hepatoportal arteriovenous fistula. A fatal hemorrhage was frequently encountered in the patients with the fistula. It was suggested that a rational treatment for those with the triple lesions--hepatoma, esophageal varices and hepatoportal arteriovenous fistula--may be ligation of the hepatic artery."}
{"id": "PMID:197652", "title": "Spinal cord arteriovenous malformations and the Klippel-Trenaunay-Weber syndrome.", "content": "Five cases in which the Klippel-Trenaunay-Weber syndrome was associated with a spinal cord arteriovenous malformation are reported: they formed part of a series of 150 spinal arteriovenous malformations. Hypertrophic lesions, dilated arteries and varicose veins were present in every case, but cutaneous angiomatosis was found in only two. In each case, there was an intramedullary AVM. The relationship of the Klippel-Trenaunay-Weber syndrome to the regional angiomatous phacomatoses is discussed.", "contents": "Spinal cord arteriovenous malformations and the Klippel-Trenaunay-Weber syndrome. Five cases in which the Klippel-Trenaunay-Weber syndrome was associated with a spinal cord arteriovenous malformation are reported: they formed part of a series of 150 spinal arteriovenous malformations. Hypertrophic lesions, dilated arteries and varicose veins were present in every case, but cutaneous angiomatosis was found in only two. In each case, there was an intramedullary AVM. The relationship of the Klippel-Trenaunay-Weber syndrome to the regional angiomatous phacomatoses is discussed."}
{"id": "PMID:197653", "title": "The enhancement of adenyl cyclase by steroid therapy in shock.", "content": "Hepatic and intestinal adenyl cyclase activity were measured after a single pulse injection of epinephrine or glucagon into normal dogs and into dogs subjected to hemorrhagic shock. The results indicated that hemorrhagic shock abolishes the increase in adenyl cyclase activity seen in normal animals following epinephrine and significantly reduces that induced by glucagon. These changes are reflected in the glucose production from the liver induced by these hormones. The response of adenyl cyclase to the in vitro addition of epinephrine or glucagon, as well as the nonspecific stimulator of adenyl cyclase, sodium fluoride, showed that it is the receptor site of the enzyme which is affected primarily by shock. The treatment of dogs with 30 mg/kg of methylprednisolone following the reinfusion of shed blood significantly improved the response of adneyl cyclase to epinephrine in both liver and intestine, and this improvement was reflected in the glucose production by the liver in response to the hormone.", "contents": "The enhancement of adenyl cyclase by steroid therapy in shock. Hepatic and intestinal adenyl cyclase activity were measured after a single pulse injection of epinephrine or glucagon into normal dogs and into dogs subjected to hemorrhagic shock. The results indicated that hemorrhagic shock abolishes the increase in adenyl cyclase activity seen in normal animals following epinephrine and significantly reduces that induced by glucagon. These changes are reflected in the glucose production from the liver induced by these hormones. The response of adenyl cyclase to the in vitro addition of epinephrine or glucagon, as well as the nonspecific stimulator of adenyl cyclase, sodium fluoride, showed that it is the receptor site of the enzyme which is affected primarily by shock. The treatment of dogs with 30 mg/kg of methylprednisolone following the reinfusion of shed blood significantly improved the response of adneyl cyclase to epinephrine in both liver and intestine, and this improvement was reflected in the glucose production by the liver in response to the hormone."}
{"id": "PMID:197658", "title": "The effects of methylxanthines on catecholamine-stimulated and normal chick embryos.", "content": "Dose of theophylline and caffeine which do not produce aortic arch anomalies in embryonic chicks have been shown to potentiate catecholamine-induced aortic arch malformations in that experimental animal. Theophylline (2.1 X 10(-5) mole per milliliter isotonic saline solution) potentiated the effective dose of norepinephrine more than 100 times. The greatest potentiation observed with epinephrine (2.5 X) was induced by 2.6 X 10(-5) mole caffeine. This study also demonstrated that both methylxanthines specifically induce aneurysms of the ascending aorta and complete absence (or nearly complete constriction) of the right ductus arteriosus. The incidences of these types of cardiovascular malformations proved to be dose dependent with theophylline a more potent teratogen than caffeine. The mobilization of calcium and/or cyclic nucleotide phosphodiesterase inhibition by the methylxanthines are suggested as significant actions in the potentiation of catecholamine-induced aortic arch anomalies.", "contents": "The effects of methylxanthines on catecholamine-stimulated and normal chick embryos. Dose of theophylline and caffeine which do not produce aortic arch anomalies in embryonic chicks have been shown to potentiate catecholamine-induced aortic arch malformations in that experimental animal. Theophylline (2.1 X 10(-5) mole per milliliter isotonic saline solution) potentiated the effective dose of norepinephrine more than 100 times. The greatest potentiation observed with epinephrine (2.5 X) was induced by 2.6 X 10(-5) mole caffeine. This study also demonstrated that both methylxanthines specifically induce aneurysms of the ascending aorta and complete absence (or nearly complete constriction) of the right ductus arteriosus. The incidences of these types of cardiovascular malformations proved to be dose dependent with theophylline a more potent teratogen than caffeine. The mobilization of calcium and/or cyclic nucleotide phosphodiesterase inhibition by the methylxanthines are suggested as significant actions in the potentiation of catecholamine-induced aortic arch anomalies."}
{"id": "PMID:197662", "title": "[Influence of dose-time relationship on the pathogenesis of peripheral neuropathy (author's transl)].", "content": "The development of peripheral neuropathies of cranial nerves and of the brachial plexus following curative deoses of irradiation is closely related with the total applied, the number and size of the individual doses per fraction and the overall time. Additional important factors for the occurrence of these late complications are the volume of tissue irradiated and the stage of disease. In the pathogenesis of peripheral neuropathy a combined effect of different factors seems likely.", "contents": "[Influence of dose-time relationship on the pathogenesis of peripheral neuropathy (author's transl)]. The development of peripheral neuropathies of cranial nerves and of the brachial plexus following curative deoses of irradiation is closely related with the total applied, the number and size of the individual doses per fraction and the overall time. Additional important factors for the occurrence of these late complications are the volume of tissue irradiated and the stage of disease. In the pathogenesis of peripheral neuropathy a combined effect of different factors seems likely."}
{"id": "PMID:197664", "title": "[The biological behavior of adenocystic carcinomas of the mouth cavity].", "content": "During the years 1965-1976, 19 patients with adenocystocarcinoma have been treated by the author on an inpatient basis. There were 15 cases with primary tumours and 4 cases of recurrences (2 of them with distant metastases). Up to now, 8 patients have died of the tumour. The mean length of survival of these patients was 51 months; that of the patients still alive, 84 months. These results lead to the conclusion that adenocystocarcinomata develop very slowly, affect mainly the accessory salivary glands and show lymphogenous and haematogenous metastasization even without previous recurrence. Radical surgical therapy of the primary tumour is advocated also in patients presenting with distant metastases.", "contents": "[The biological behavior of adenocystic carcinomas of the mouth cavity]. During the years 1965-1976, 19 patients with adenocystocarcinoma have been treated by the author on an inpatient basis. There were 15 cases with primary tumours and 4 cases of recurrences (2 of them with distant metastases). Up to now, 8 patients have died of the tumour. The mean length of survival of these patients was 51 months; that of the patients still alive, 84 months. These results lead to the conclusion that adenocystocarcinomata develop very slowly, affect mainly the accessory salivary glands and show lymphogenous and haematogenous metastasization even without previous recurrence. Radical surgical therapy of the primary tumour is advocated also in patients presenting with distant metastases."}
{"id": "PMID:197668", "title": "[Demonstrating the localization of hemoproteins by an electron cytochemical method].", "content": "The dynamics of division and interphase cell size in the growing ovule of Pinus silvestris was studied on histological slides in the year of fertilization. A constant extension in size of dividing cells of the endosperm was shown which, in this respect, do not differ much from the interphase ones. Cell division and elongation in this tissue occur simultaneously to be completed only with the transition of cell to differentiation. The size extention of the dividing cell does not influence the frequency of cell division. In the integument and the nucleus, the value of dividing cells is relatively constant. At the transition of these cells to elongation their mitotic activity decreases shaply to stop completely after-wards. Cell division and elongation are divided here in time.", "contents": "[Demonstrating the localization of hemoproteins by an electron cytochemical method]. The dynamics of division and interphase cell size in the growing ovule of Pinus silvestris was studied on histological slides in the year of fertilization. A constant extension in size of dividing cells of the endosperm was shown which, in this respect, do not differ much from the interphase ones. Cell division and elongation in this tissue occur simultaneously to be completed only with the transition of cell to differentiation. The size extention of the dividing cell does not influence the frequency of cell division. In the integument and the nucleus, the value of dividing cells is relatively constant. At the transition of these cells to elongation their mitotic activity decreases shaply to stop completely after-wards. Cell division and elongation are divided here in time."}
{"id": "PMID:197669", "title": "[Analysis of substances issuing from Zajdela ascitic hepatoma cells following exposure to UV radiation of different wavelength. II. Proton release].", "content": "The release of protein from the Zaidela ascitic hepatoma cells following irradiation with physiological doses of short-wave (254 nm) and long-wave (300--380 nm) UV light (far and near UV radiation) has been investigated. The amount of protein increases with dose making, upon the maximal radiation damage, 180 and 2 per cent of the protein against, resp., the protein amount releasing from non-treated cells and the total protein of the intact cell. The far UV light is by one order more efficient than the near UV light. Irradiation of cells with the former and the latter results in the release of high and low molecular proteins, resp. The near UV irradiation brings about heavier releasing of proteins than does the far UV light.", "contents": "[Analysis of substances issuing from Zajdela ascitic hepatoma cells following exposure to UV radiation of different wavelength. II. Proton release]. The release of protein from the Zaidela ascitic hepatoma cells following irradiation with physiological doses of short-wave (254 nm) and long-wave (300--380 nm) UV light (far and near UV radiation) has been investigated. The amount of protein increases with dose making, upon the maximal radiation damage, 180 and 2 per cent of the protein against, resp., the protein amount releasing from non-treated cells and the total protein of the intact cell. The far UV light is by one order more efficient than the near UV light. Irradiation of cells with the former and the latter results in the release of high and low molecular proteins, resp. The near UV irradiation brings about heavier releasing of proteins than does the far UV light."}
{"id": "PMID:197665", "title": "Report of Joint Committee for Stroke Resources. IV. Brain edema in stroke.", "content": "A classification of brain edema is provided as well as an extensive review of the animal models from which we have derived most of the basic information we have about the formation and resolution of edema. The clinical aspects of cerebral edema in stroke are discussed and also modern methods for identifying cerebral edema in the human. Attention is given to computed tomography and enhanced CT and advances in their application to this condition. Treatment of cerebral edema in the stroke patient using glycerol, dextran 40, mannitol, steroids, and other drugs is discussed and the need pointed out for controlled clinical trials of the therapeutic effectiveness of these agents.", "contents": "Report of Joint Committee for Stroke Resources. IV. Brain edema in stroke. A classification of brain edema is provided as well as an extensive review of the animal models from which we have derived most of the basic information we have about the formation and resolution of edema. The clinical aspects of cerebral edema in stroke are discussed and also modern methods for identifying cerebral edema in the human. Attention is given to computed tomography and enhanced CT and advances in their application to this condition. Treatment of cerebral edema in the stroke patient using glycerol, dextran 40, mannitol, steroids, and other drugs is discussed and the need pointed out for controlled clinical trials of the therapeutic effectiveness of these agents."}
{"id": "PMID:197670", "title": "[Prospects for use of the anterior chamber of the eye for studying proliferation, differentiation and hybridization of tumor cells].", "content": "The anterior chamber of mammalian eye (ACE) is one of the places of organism privileged immunologically that permits to use it for transplantations of allogenic tissues. Besides, the medium filling the chamber, provides an excellent growth of transplants there, whereas the transparent cornea allows to control the growth. The analysis of results obtained with this method shows its acceptibility both for heterotransplantations of tumors including human tumors, and for homotransplantations with the aim to study the progression of tumors and the selection of constant tumor lines. The ACE is easily applicable for studying morphogenetic potentialities of tumor cells, as well as their ability to differentiation and normalization, because its medium has the quality of \"differentiating\" for many tissues. Cytological heterogeneity, revealed during tumor transplantations, allows to study the spectrum of cytological variability and transgression of tumor characters at different stages of their progression. The ACE can be used for estimation of tumor formation ability of tumor cells by determining TD50 (tumor dosis 50) which is important for estimation of different kinds of damage (X-rays, chemotherapy etc.). According to authors' point of view, it is very perspective to use the anterior chamber of eye for elaboration of effective methods of hybridization tumor cells with normal ones.", "contents": "[Prospects for use of the anterior chamber of the eye for studying proliferation, differentiation and hybridization of tumor cells]. The anterior chamber of mammalian eye (ACE) is one of the places of organism privileged immunologically that permits to use it for transplantations of allogenic tissues. Besides, the medium filling the chamber, provides an excellent growth of transplants there, whereas the transparent cornea allows to control the growth. The analysis of results obtained with this method shows its acceptibility both for heterotransplantations of tumors including human tumors, and for homotransplantations with the aim to study the progression of tumors and the selection of constant tumor lines. The ACE is easily applicable for studying morphogenetic potentialities of tumor cells, as well as their ability to differentiation and normalization, because its medium has the quality of \"differentiating\" for many tissues. Cytological heterogeneity, revealed during tumor transplantations, allows to study the spectrum of cytological variability and transgression of tumor characters at different stages of their progression. The ACE can be used for estimation of tumor formation ability of tumor cells by determining TD50 (tumor dosis 50) which is important for estimation of different kinds of damage (X-rays, chemotherapy etc.). According to authors' point of view, it is very perspective to use the anterior chamber of eye for elaboration of effective methods of hybridization tumor cells with normal ones."}
{"id": "PMID:197671", "title": "[Effect of colchamine on the morphology of transformed fibroblast-like cells in culture].", "content": "Colcemid-induced changes in the morphology of cultured transformed fibroblast-like mouse cells were studied using scanning electron microscope. Colcemid interferes with the normal cell polarization so that all the cell edges became active. Colcemid-treated normal cells remained well spread over the substrate. Transformed cells lost their polarization after colcemid treatment--the long, narrow, poorly attached processes of different form appeared along all the cell periphery. As in the case of the absence of colcemid, transformed cells remained less spread and worse attached to the substrate than normal ones. It is suggests that a) the same colcemid-sensitive structures are responsible for the polarization of transformed and normal cells; b) morphological differences between transformed and normal cells are determined mainly by structures different from colcemide-sensitive ones.", "contents": "[Effect of colchamine on the morphology of transformed fibroblast-like cells in culture]. Colcemid-induced changes in the morphology of cultured transformed fibroblast-like mouse cells were studied using scanning electron microscope. Colcemid interferes with the normal cell polarization so that all the cell edges became active. Colcemid-treated normal cells remained well spread over the substrate. Transformed cells lost their polarization after colcemid treatment--the long, narrow, poorly attached processes of different form appeared along all the cell periphery. As in the case of the absence of colcemid, transformed cells remained less spread and worse attached to the substrate than normal ones. It is suggests that a) the same colcemid-sensitive structures are responsible for the polarization of transformed and normal cells; b) morphological differences between transformed and normal cells are determined mainly by structures different from colcemide-sensitive ones."}
{"id": "PMID:197672", "title": "Allelic structural genes for the expression of mature of immature endogenous type-C virus in C57BL/he and C57BL/6J mice.", "content": "Type C particles produced in a great amount by the exocrine pancreas of normal C57BL mice have been found by electron microscopy to retain their immature morphology in C57BL/6J mice and to develop into the mature form in C57BL/He mice. Examining F1, F2 and BC1 hybrids between the 2 strains, evidence of a dominant allelism for the immature phenotype was found.", "contents": "Allelic structural genes for the expression of mature of immature endogenous type-C virus in C57BL/he and C57BL/6J mice. Type C particles produced in a great amount by the exocrine pancreas of normal C57BL mice have been found by electron microscopy to retain their immature morphology in C57BL/6J mice and to develop into the mature form in C57BL/He mice. Examining F1, F2 and BC1 hybrids between the 2 strains, evidence of a dominant allelism for the immature phenotype was found."}
{"id": "PMID:197673", "title": "[Quaternary structure of NAD-kinase from rabbit skeletal muscles].", "content": "The quaternary structure and some kinetic properties were studied for NAD-kinase from the rabbit skeletal muscles. The molecular weight of the 150-300-fold purified enzymic preparation was determined by separation in the Sephadex G-200 thin layer, by means of Sephadex G-200 column gel-filtration and by the method of electrophoresis in the gradient of polyacrylamide gel concentration. Some molecular forms of NAD-kinase with a molecular weight of 31000-305000 are found in the enzymic preparation and possibility to change from one form to another is shown. On the basis of the established quaternary structure and complex kinetic characteristics of the enzyme a conclusion is drawn on the existence of the rabbit skeletal muscle NAD-kinase as an equilibrium system of the oligomeric forms possessing different catalytic activity and consisting of different combinations of subunits with a molecular weight of 31000.", "contents": "[Quaternary structure of NAD-kinase from rabbit skeletal muscles]. The quaternary structure and some kinetic properties were studied for NAD-kinase from the rabbit skeletal muscles. The molecular weight of the 150-300-fold purified enzymic preparation was determined by separation in the Sephadex G-200 thin layer, by means of Sephadex G-200 column gel-filtration and by the method of electrophoresis in the gradient of polyacrylamide gel concentration. Some molecular forms of NAD-kinase with a molecular weight of 31000-305000 are found in the enzymic preparation and possibility to change from one form to another is shown. On the basis of the established quaternary structure and complex kinetic characteristics of the enzyme a conclusion is drawn on the existence of the rabbit skeletal muscle NAD-kinase as an equilibrium system of the oligomeric forms possessing different catalytic activity and consisting of different combinations of subunits with a molecular weight of 31000."}
{"id": "PMID:197674", "title": "[Relation between catecholamines metabolism and CoA content in rat tissues].", "content": "The content of CoA in the liver, heart, kidneys and brain of rats was studied as affected by ACTH, melipramine and prednisolone. After ACTH administration the content of CoA in the liver increases. When blocking \"capture\" and \"reverse capture\" of catecholamines by melipramine the content of CoA in the kidneys lowers. Administration of melipramines causes no changes in the content of CoA in the tissues. Under the effect of prednisolone there is a tendency to the CoA content decrease in the kidneys. In the other tissues the subcutaneous administration of the preparations does not effect the content of CoA. Possible mechanism of the studied pharmacologic substances effect on the content of CoA in the tissues is under discussion.", "contents": "[Relation between catecholamines metabolism and CoA content in rat tissues]. The content of CoA in the liver, heart, kidneys and brain of rats was studied as affected by ACTH, melipramine and prednisolone. After ACTH administration the content of CoA in the liver increases. When blocking \"capture\" and \"reverse capture\" of catecholamines by melipramine the content of CoA in the kidneys lowers. Administration of melipramines causes no changes in the content of CoA in the tissues. Under the effect of prednisolone there is a tendency to the CoA content decrease in the kidneys. In the other tissues the subcutaneous administration of the preparations does not effect the content of CoA. Possible mechanism of the studied pharmacologic substances effect on the content of CoA in the tissues is under discussion."}
{"id": "PMID:197680", "title": "Granular myoblastoma: perineal neoplasm of probable neural origin.", "content": "A seventy-year-old man with a painless, perineal neoplasm was found to have a granular cell myoblastoma densely adherent to the bulbar urethra. This case represents the fourth known perineal neoplasm of neural origin.", "contents": "Granular myoblastoma: perineal neoplasm of probable neural origin. A seventy-year-old man with a painless, perineal neoplasm was found to have a granular cell myoblastoma densely adherent to the bulbar urethra. This case represents the fourth known perineal neoplasm of neural origin."}
{"id": "PMID:197675", "title": "[Differences in transcription of nuclear RNA from rat liver with normal and malignant growth].", "content": "Total nuclear RNA was isolated under conditions of actinomycin D blocking ion-exchange chromatography on kieselguhr columns with methylated albumin detected differences in transpiration of rat liver nuclear RNA with intensive normal and malignant growth. Actinomycin D in doses blocking the appearance of peculiar proteins in the blood serum of rats with the regenerating liver and RS-1 hepatoma produces a different effect on the biosynthesis of nuclear DNA-like RNA of the rat liver. 24h after a partial hepatectomy the antibiotic inhibits considerably the biosynthesis of nuclear DNA-like RNA which is eluated during chromatographying with 0.2% solution of sodium dodecyl sulphate at 70 degrees C. With RS-1 hepatoma the actinomycin D effect is most pronounced with respect to nuclear DNA-like RNA of rats with a tumour which is washed off from the column with a 0.2% solution of sodium dodecyl sulphate at 37 degrees C.", "contents": "[Differences in transcription of nuclear RNA from rat liver with normal and malignant growth]. Total nuclear RNA was isolated under conditions of actinomycin D blocking ion-exchange chromatography on kieselguhr columns with methylated albumin detected differences in transpiration of rat liver nuclear RNA with intensive normal and malignant growth. Actinomycin D in doses blocking the appearance of peculiar proteins in the blood serum of rats with the regenerating liver and RS-1 hepatoma produces a different effect on the biosynthesis of nuclear DNA-like RNA of the rat liver. 24h after a partial hepatectomy the antibiotic inhibits considerably the biosynthesis of nuclear DNA-like RNA which is eluated during chromatographying with 0.2% solution of sodium dodecyl sulphate at 70 degrees C. With RS-1 hepatoma the actinomycin D effect is most pronounced with respect to nuclear DNA-like RNA of rats with a tumour which is washed off from the column with a 0.2% solution of sodium dodecyl sulphate at 37 degrees C."}
{"id": "PMID:197676", "title": "[Peptide hydrolase activity in rabbit brain subcellular fractions under conditions of adrenalectomy and administration of hydrocortisone and ACTH].", "content": "Adrenalectomy and administration of hydrocortisone and ACTH are shown to induce no changes in the total activity of neutral peptide-hydrolase in both homogenates and brain subcellular fractions. The absence of adrenalectomy and hormone administration effect on the total peptide-hydrolase activity in homogenates is established simultaneously with its essential changes in the brain subcellular fractions. A decrease in the enzymic activity of the mitochondrial-lysosomal fraction (MLF) following adrenalectomy is observed side by side with its increase in a soluble fraction. Hydrocortisone and ACTH administration cause an increase in the acid peptide-hydrolase activity in MLF and its decrease in the brain soluble and microsomal fractions of adrenalectomized rabbits. The degree of solubilization of MLF acid and neutral peptide-hydrolase by detergent triton X-100 after adrenalectomy is increased. Hydrocortisone and ACTH administration, on the contrary, decrease a degree of solubilization of the brain MLF peptide-hydrolase in adrenalectomized animals.", "contents": "[Peptide hydrolase activity in rabbit brain subcellular fractions under conditions of adrenalectomy and administration of hydrocortisone and ACTH]. Adrenalectomy and administration of hydrocortisone and ACTH are shown to induce no changes in the total activity of neutral peptide-hydrolase in both homogenates and brain subcellular fractions. The absence of adrenalectomy and hormone administration effect on the total peptide-hydrolase activity in homogenates is established simultaneously with its essential changes in the brain subcellular fractions. A decrease in the enzymic activity of the mitochondrial-lysosomal fraction (MLF) following adrenalectomy is observed side by side with its increase in a soluble fraction. Hydrocortisone and ACTH administration cause an increase in the acid peptide-hydrolase activity in MLF and its decrease in the brain soluble and microsomal fractions of adrenalectomized rabbits. The degree of solubilization of MLF acid and neutral peptide-hydrolase by detergent triton X-100 after adrenalectomy is increased. Hydrocortisone and ACTH administration, on the contrary, decrease a degree of solubilization of the brain MLF peptide-hydrolase in adrenalectomized animals."}
{"id": "PMID:197681", "title": "A jugular foramen schwannoma simulating an acoustic tumor with recovery of retrolabyrinthine cochleovestibular function.", "content": "Our literature review has tabulated 33 jugular foramen neuromas that appeared either as a neurologic \"syndrome of the jugular foramen\" like a glomas tumor, or similar to an acoustic tumor. The few posterior fossa tumors involving the eighth nerve or encroaching upon it that have been removed and resulted in cochleovestibular preservation or recovery have been reviewed. A rare case of jugular foramen schwannoma with cochleovestibular preservation after total removal has been extensively studied with preoperative and postoperative cochleovestibular tests.", "contents": "A jugular foramen schwannoma simulating an acoustic tumor with recovery of retrolabyrinthine cochleovestibular function. Our literature review has tabulated 33 jugular foramen neuromas that appeared either as a neurologic \"syndrome of the jugular foramen\" like a glomas tumor, or similar to an acoustic tumor. The few posterior fossa tumors involving the eighth nerve or encroaching upon it that have been removed and resulted in cochleovestibular preservation or recovery have been reviewed. A rare case of jugular foramen schwannoma with cochleovestibular preservation after total removal has been extensively studied with preoperative and postoperative cochleovestibular tests."}
{"id": "PMID:197686", "title": "[Use of inactivated vaccine against infectious rhinotracheitis--pustular vulvovaginitis (IBR-IPV) in calves and pregnant cows].", "content": "A total of twelve batches of an inactivated vaccine against IBR--IPV, obtained by the authors, were tested in the practice. Vaccinated were 212 calves and 1172 cows and heifers on five dairy farms in different communities. On the basis of virologic, serologic, clinical and epizootiologic investigations the conclusions were drawn that the vaccine is harmless and highly immunogenic. In subcutaneous application at the rate of 3 cm3, twice, it renders protection against IBR--IPV infection (respiratory diseases and abortions) to calves aged more than 30 days for at least 6 months and 8 months for pregnant cows and heifers. On farms with a record of active IBP--IPV infection it is suggested to treat both the diseased and apparently (clinically) normal calves, either therapeutically or prophylactically, with a hyperimmune serum, and after the disease has receded--to resort to vaccination. In comparison with the live vaccines the tested one has been shown to provoke no postvaccinal accidents, eliminating the possibility of maintaining and widening the active infection foci, at otherwise almost comparable immunogenic properties as regards the titers of the virus-neutralizing antibodies produced after the vaccination.", "contents": "[Use of inactivated vaccine against infectious rhinotracheitis--pustular vulvovaginitis (IBR-IPV) in calves and pregnant cows]. A total of twelve batches of an inactivated vaccine against IBR--IPV, obtained by the authors, were tested in the practice. Vaccinated were 212 calves and 1172 cows and heifers on five dairy farms in different communities. On the basis of virologic, serologic, clinical and epizootiologic investigations the conclusions were drawn that the vaccine is harmless and highly immunogenic. In subcutaneous application at the rate of 3 cm3, twice, it renders protection against IBR--IPV infection (respiratory diseases and abortions) to calves aged more than 30 days for at least 6 months and 8 months for pregnant cows and heifers. On farms with a record of active IBP--IPV infection it is suggested to treat both the diseased and apparently (clinically) normal calves, either therapeutically or prophylactically, with a hyperimmune serum, and after the disease has receded--to resort to vaccination. In comparison with the live vaccines the tested one has been shown to provoke no postvaccinal accidents, eliminating the possibility of maintaining and widening the active infection foci, at otherwise almost comparable immunogenic properties as regards the titers of the virus-neutralizing antibodies produced after the vaccination."}
{"id": "PMID:197683", "title": "Ultrasonic evaluation of salivary glands.", "content": "Diagnostic ultrasound was used to study 40 patients undergoing excision of a major salivary gland for various disease entities. Findings were as follows: Malignant lesions showed low reflectivity and attenuation with poorly outlined or diffuse borders. Inflammation demonstrated high reflectivity and attentuation with diffuse borders. Echographic patterns from mixed tumors showed either high or medium to low reflectivity; all demonstrated low to medium attenuation and were well outlined. It appears that various diseases of the major salivary glands have different echographic patterns. An attempt to correlate the echographic patterns with the histology of the disease process was made.", "contents": "Ultrasonic evaluation of salivary glands. Diagnostic ultrasound was used to study 40 patients undergoing excision of a major salivary gland for various disease entities. Findings were as follows: Malignant lesions showed low reflectivity and attenuation with poorly outlined or diffuse borders. Inflammation demonstrated high reflectivity and attentuation with diffuse borders. Echographic patterns from mixed tumors showed either high or medium to low reflectivity; all demonstrated low to medium attenuation and were well outlined. It appears that various diseases of the major salivary glands have different echographic patterns. An attempt to correlate the echographic patterns with the histology of the disease process was made."}
{"id": "PMID:197688", "title": "Microscopic and pulse cytophotometric investigation of a carcinoma of the jejumum in a seven year old child.", "content": "In a seven year old boy with acute abdominal pain and intestinal bleeding, laparotomy revealed an invaginated carcinoma adenomatosum cylindrocellulare in the distal part of the jejunum. Histological and pulse cytophotometric investigations support the diagnosis of a highly differentiated but locally destructive and malignant tumor.", "contents": "Microscopic and pulse cytophotometric investigation of a carcinoma of the jejumum in a seven year old child. In a seven year old boy with acute abdominal pain and intestinal bleeding, laparotomy revealed an invaginated carcinoma adenomatosum cylindrocellulare in the distal part of the jejunum. Histological and pulse cytophotometric investigations support the diagnosis of a highly differentiated but locally destructive and malignant tumor."}
{"id": "PMID:197692", "title": "Interaction between ceruloplasmin and Sendai virus envolpe components. Note IV. Effect of ceruloplasmin on the hemagglutinin and neuraminidase activities of Tween 20-solubilized envelope components separated by adsorption--elution on RBC.", "content": "Ceruloplasmin inhibits the hemagglutinin (HA) and neuraminidase (N-ase) activities of envelope fragment populations isolated from Sendai virus disrupted by alkali--Tween 20 treatment. The inhibition induced differs according to adsorption--elution characteristics, value and ratio of HA and N-ase activities and sterical configuration of the envelope fragments.", "contents": "Interaction between ceruloplasmin and Sendai virus envolpe components. Note IV. Effect of ceruloplasmin on the hemagglutinin and neuraminidase activities of Tween 20-solubilized envelope components separated by adsorption--elution on RBC. Ceruloplasmin inhibits the hemagglutinin (HA) and neuraminidase (N-ase) activities of envelope fragment populations isolated from Sendai virus disrupted by alkali--Tween 20 treatment. The inhibition induced differs according to adsorption--elution characteristics, value and ratio of HA and N-ase activities and sterical configuration of the envelope fragments."}
{"id": "PMID:197707", "title": "[Effect of 5-fluorouracil and thiophosphamide on the activity and fractional content of phosphatases of Zajdela hepatoma].", "content": "The administration of different types of antitumor drugs is found to lead to a decrease in total activity of phosphatases in mitochondrial, lysosomal and microsomal fraction of Zajdela hepatoma cells, the free activity being enhanced. The isoenzyme pattern of phosphatases in soluble fraction is influenced too. The results suggest that different antitumor drugs cause a uniform response in tumor cells, manifested in disorders in the protein synthesizing system and membranes of subcellular particles involved.", "contents": "[Effect of 5-fluorouracil and thiophosphamide on the activity and fractional content of phosphatases of Zajdela hepatoma]. The administration of different types of antitumor drugs is found to lead to a decrease in total activity of phosphatases in mitochondrial, lysosomal and microsomal fraction of Zajdela hepatoma cells, the free activity being enhanced. The isoenzyme pattern of phosphatases in soluble fraction is influenced too. The results suggest that different antitumor drugs cause a uniform response in tumor cells, manifested in disorders in the protein synthesizing system and membranes of subcellular particles involved."}
{"id": "PMID:197709", "title": "[Influence of diets with a high content of qualitatively different carbohydrates on the metabolism of blood lipoproteins].", "content": "The feeding of rats for a space of 30 days on diets with elevated content of starch or saccharose (71 per cent of the total calorific value) was followed by an accelerated synthesis and secretion into the blood of pre-beta-lipoproteins. The ration with succharose, however, produced a much greater effect on the rate of synthesis of pre-beta-lipoproteins than did the one containing starch. The action of both carbohydrate-rich rations was noted to be attended by a growing rate of the apoproteids and glycerides exchange in the low-density lipoproteins. The feature distinguishing the effect produced by the ration with saccharose, as compared with that containing starch, was an accelerated etherification of cholesterol in the blood.", "contents": "[Influence of diets with a high content of qualitatively different carbohydrates on the metabolism of blood lipoproteins]. The feeding of rats for a space of 30 days on diets with elevated content of starch or saccharose (71 per cent of the total calorific value) was followed by an accelerated synthesis and secretion into the blood of pre-beta-lipoproteins. The ration with succharose, however, produced a much greater effect on the rate of synthesis of pre-beta-lipoproteins than did the one containing starch. The action of both carbohydrate-rich rations was noted to be attended by a growing rate of the apoproteids and glycerides exchange in the low-density lipoproteins. The feature distinguishing the effect produced by the ration with saccharose, as compared with that containing starch, was an accelerated etherification of cholesterol in the blood."}
{"id": "PMID:197713", "title": "[Several virologic and biochemical aspects of vaccination with antipoliomyelitis vaccine. Fate of the parent virus].", "content": "In the present study we attempted to follow the fate of the parental poliomyelitis virus of immunological type II labeled with 3H-uridine in vaccinated animals. For this purpose, 3H-uridine labeled purified and concentrated virus was inoculated intramuscularly into cotton rats (sensitive to poliomyelitis virus) and guinea pigs (insensitive to poliomyelitis virus). The controls consisted of two groups of the same animal species: the animals of the first group were inoculated intramuscularly with pure 3H-uridine of known high activity while the animals of the second group were inoculated also intramuscularly with pure 3H-uridine and in another leg 0.5 ml of standard poliovirus vaccine of type II. Since poliomyelitis virus replicates in the cytoplasm, we studied cytoplasmic extracts of various organs (the brain, spinal cord, lungs, and spleen) of cotton rats and guinea pigs at different intervals after virus inoculation (1, 4, and 15 days). The experimental results showed the attenuated type II poliomyelitis virus to be able to persist for long periods in animals in the form of subviral particles with a higher buoyant density in cesium chloride gradient.", "contents": "[Several virologic and biochemical aspects of vaccination with antipoliomyelitis vaccine. Fate of the parent virus]. In the present study we attempted to follow the fate of the parental poliomyelitis virus of immunological type II labeled with 3H-uridine in vaccinated animals. For this purpose, 3H-uridine labeled purified and concentrated virus was inoculated intramuscularly into cotton rats (sensitive to poliomyelitis virus) and guinea pigs (insensitive to poliomyelitis virus). The controls consisted of two groups of the same animal species: the animals of the first group were inoculated intramuscularly with pure 3H-uridine of known high activity while the animals of the second group were inoculated also intramuscularly with pure 3H-uridine and in another leg 0.5 ml of standard poliovirus vaccine of type II. Since poliomyelitis virus replicates in the cytoplasm, we studied cytoplasmic extracts of various organs (the brain, spinal cord, lungs, and spleen) of cotton rats and guinea pigs at different intervals after virus inoculation (1, 4, and 15 days). The experimental results showed the attenuated type II poliomyelitis virus to be able to persist for long periods in animals in the form of subviral particles with a higher buoyant density in cesium chloride gradient."}
{"id": "PMID:197718", "title": "[A simple micro-procedure in virological and serological diagnosis].", "content": "The author reports on a micro-neutralization test which makes it possible to detect the antibodies against 7 different respiratory viruses (adeno and parainfluenza viruses) using only 0.080 ml of serum from patient. Swaged PVC foil used for packing pharmaceuticals, also known here as strip packing or press-through packing for pills and dragees was employed as plates for the cultures. This material is not toxic for the cell cultures, it is cheap and suitable also for other microbiological work in the field of serology.", "contents": "[A simple micro-procedure in virological and serological diagnosis]. The author reports on a micro-neutralization test which makes it possible to detect the antibodies against 7 different respiratory viruses (adeno and parainfluenza viruses) using only 0.080 ml of serum from patient. Swaged PVC foil used for packing pharmaceuticals, also known here as strip packing or press-through packing for pills and dragees was employed as plates for the cultures. This material is not toxic for the cell cultures, it is cheap and suitable also for other microbiological work in the field of serology."}
{"id": "PMID:197714", "title": "[Several virologic and biochemical aspects of vaccination with antipoliomyelitis vaccine. Characteristics of intracellular virus-specific structures].", "content": "The data are presented concerning infectious potentials of subvirus particles isolated from cytoplasmic extracts of various organs of cotton rats and guinea pigs inoculated intramuscularly with purified and concentrated poliomyelitis virus type II. As described earlier, from various organs of the animals (the brain, spinal cord, lungs, and spleen) subvirus particles were isolated which in cesium chloride gradient had a density higher by 0.05-0.1 g/ml than that of the intact virus. Determinations of the infectious titre of these subparticles in susceptible cells showed their infectivity to be lower by 4-5 lg than that of the infact virus. When DEAE-dextran was used, a titre of both subvirus particles isolated from cytoplasmic extracts of various organs of the immunized animals and of the original poliomyelitis virus increased by 3-4 lg. The subvirus particles were sensitive to pancreatic RN-ase and to the antiserum against poliovirus type II. All the foregoing permits a conclusion that attenuated type II poliovirus or a portion of its population after inoculation into the living body is capable of long-term persistence there in the form of subviral particles with high buoyant density values.", "contents": "[Several virologic and biochemical aspects of vaccination with antipoliomyelitis vaccine. Characteristics of intracellular virus-specific structures]. The data are presented concerning infectious potentials of subvirus particles isolated from cytoplasmic extracts of various organs of cotton rats and guinea pigs inoculated intramuscularly with purified and concentrated poliomyelitis virus type II. As described earlier, from various organs of the animals (the brain, spinal cord, lungs, and spleen) subvirus particles were isolated which in cesium chloride gradient had a density higher by 0.05-0.1 g/ml than that of the intact virus. Determinations of the infectious titre of these subparticles in susceptible cells showed their infectivity to be lower by 4-5 lg than that of the infact virus. When DEAE-dextran was used, a titre of both subvirus particles isolated from cytoplasmic extracts of various organs of the immunized animals and of the original poliomyelitis virus increased by 3-4 lg. The subvirus particles were sensitive to pancreatic RN-ase and to the antiserum against poliovirus type II. All the foregoing permits a conclusion that attenuated type II poliovirus or a portion of its population after inoculation into the living body is capable of long-term persistence there in the form of subviral particles with high buoyant density values."}
{"id": "PMID:197715", "title": "[Antiviral activity of experimental combination of 5-iodo-2-deoxyuridine with 6-azauridine and its effectiveness in the treatment of herpetic infection with lesions of the skin and mucous membranes].", "content": "The use of the combination of 5-iodo-2-dioxyuridine (IUDR) and 6-azauridine drugs differing in their mechanisms of action in an experimental herpetic infection demonstrated its definite antiviral activity, not only not inferior to the effect of each of the drugs alone, but also remaining sufficiently high when the concentration of IUDR was decreased 2-fold. In clinical trials in relapsing genital herpes all the drugs under study showed statistically significant therapeutic activity. The combined use of the drugs exerted a certain synergistic effect.", "contents": "[Antiviral activity of experimental combination of 5-iodo-2-deoxyuridine with 6-azauridine and its effectiveness in the treatment of herpetic infection with lesions of the skin and mucous membranes]. The use of the combination of 5-iodo-2-dioxyuridine (IUDR) and 6-azauridine drugs differing in their mechanisms of action in an experimental herpetic infection demonstrated its definite antiviral activity, not only not inferior to the effect of each of the drugs alone, but also remaining sufficiently high when the concentration of IUDR was decreased 2-fold. In clinical trials in relapsing genital herpes all the drugs under study showed statistically significant therapeutic activity. The combined use of the drugs exerted a certain synergistic effect."}
{"id": "PMID:197721", "title": "Carcinogenicity of nitrosoazetidine and tetradeuteronitrosoazetidine in Sprague-Dawley Rats.", "content": "Nitrosoazetidine was fed to rats in drinking water at three different concentrations. At 2 mmol (10 mmol total dose) all of the rats died with hepatocellular carcinomas by the 62nd week. This was a greater response than to an equivalent dose of nitrosopyrrolidine. At 0.67 mmol, 6 of 21 rats developed liver tumors, and at 0.17 millimolar 2 of 30 animals had liver tumors. The comparable responses to feeding of nitrosoazetidine-2,2,4,4-d4 were 3 of 21 rats with liver tumors at 0.69 millimolar and 3 of 30 rats with liver tumors at 0.17 mmol. These results show only a small deuterium isotope effect in liver carcinogenesis with nitrosoazetidine.", "contents": "Carcinogenicity of nitrosoazetidine and tetradeuteronitrosoazetidine in Sprague-Dawley Rats. Nitrosoazetidine was fed to rats in drinking water at three different concentrations. At 2 mmol (10 mmol total dose) all of the rats died with hepatocellular carcinomas by the 62nd week. This was a greater response than to an equivalent dose of nitrosopyrrolidine. At 0.67 mmol, 6 of 21 rats developed liver tumors, and at 0.17 millimolar 2 of 30 animals had liver tumors. The comparable responses to feeding of nitrosoazetidine-2,2,4,4-d4 were 3 of 21 rats with liver tumors at 0.69 millimolar and 3 of 30 rats with liver tumors at 0.17 mmol. These results show only a small deuterium isotope effect in liver carcinogenesis with nitrosoazetidine."}
{"id": "PMID:197717", "title": "Mechanism and control of fluid secretion.", "content": "Fluid secretion and reabsorption by a variety of plant and animal tissues appear to be accomplished by osmotic coupling between solute transport and water movement. The local osmosis model suggests that active accumulation of solutes within narrow folds at the cell surface may produce the local gradients that generate water flow. Both micropuncture techniques and electron-probe X-ray microanalysis have established that local osmotic gradients occur in absorptive epithelia, but they have not as yet been detected in secretory tissues.Hormonal control of secretion involves stimulation of solute pumps and adjustments of permeability to non-transported solutes. Since hormone receptors and pumps are often located on opposite surfaces of the cell, intracellular second messengers convey the secretory signal through cytoplasm. Much has been learned by study of insect tissues that are anatomically simple and that function for long periods in vitro. Aspects of hormone-receptor interaction have been explored, including the action of halluninogenic molecules. In insect salivary glands cyclic AMP appears to stimulate cation transport, while calcium increases anion permeability. The various second messengers probably interact with each other in complex feedback loops that stabilize the system and make it quickly responsive to hormone. Cyclic AMP may stimulate release of calcium from mitochondria. Unresolved is the way second messengers alter properties of the cell surface.", "contents": "Mechanism and control of fluid secretion. Fluid secretion and reabsorption by a variety of plant and animal tissues appear to be accomplished by osmotic coupling between solute transport and water movement. The local osmosis model suggests that active accumulation of solutes within narrow folds at the cell surface may produce the local gradients that generate water flow. Both micropuncture techniques and electron-probe X-ray microanalysis have established that local osmotic gradients occur in absorptive epithelia, but they have not as yet been detected in secretory tissues.Hormonal control of secretion involves stimulation of solute pumps and adjustments of permeability to non-transported solutes. Since hormone receptors and pumps are often located on opposite surfaces of the cell, intracellular second messengers convey the secretory signal through cytoplasm. Much has been learned by study of insect tissues that are anatomically simple and that function for long periods in vitro. Aspects of hormone-receptor interaction have been explored, including the action of halluninogenic molecules. In insect salivary glands cyclic AMP appears to stimulate cation transport, while calcium increases anion permeability. The various second messengers probably interact with each other in complex feedback loops that stabilize the system and make it quickly responsive to hormone. Cyclic AMP may stimulate release of calcium from mitochondria. Unresolved is the way second messengers alter properties of the cell surface."}
{"id": "PMID:197743", "title": "[Proximal ureteral atresia in childhood].", "content": "A rare cause of the congenital hydronephrosis is the proximal atresia of the ureter. With the help of 6 own cases morphology, clinic and therapy of this clinical picture are discussed. The differentiation from Wilms's tumour renders differential-diagnostic difficulties. It seems that a clinical description of this picture of a disease is hitherto not yet existing.", "contents": "[Proximal ureteral atresia in childhood]. A rare cause of the congenital hydronephrosis is the proximal atresia of the ureter. With the help of 6 own cases morphology, clinic and therapy of this clinical picture are discussed. The differentiation from Wilms's tumour renders differential-diagnostic difficulties. It seems that a clinical description of this picture of a disease is hitherto not yet existing."}
{"id": "PMID:197744", "title": "[Malignant mixed tumor of the liver in an adult (author's transl)].", "content": "A malignant mixed tumor of the liver was observed in a 55 years old woman. The tumor was composed of an adenocarcinoma, a haemangioendothe liosarcoma, and a chondrosarcoma.", "contents": "[Malignant mixed tumor of the liver in an adult (author's transl)]. A malignant mixed tumor of the liver was observed in a 55 years old woman. The tumor was composed of an adenocarcinoma, a haemangioendothe liosarcoma, and a chondrosarcoma."}
{"id": "PMID:197745", "title": "[Mortality rate after lung resection for bronchial carcinoma (author's transl)].", "content": "1351 patients with lung resection were analyzed. Lethality during hospital treatment was 6.2%. 11 patients, who died during the 6 first weeks after the resection, had occult metastases. The causes of death among these 6.2% were pulmonary embolism (40.5%), insufficiency of the bronchial stump and following complications (17.9%), pneumonia (10.7%), cardiorespiratory failure (9.5%) and intraabdominal complications (8.3%). Improving these figures should begin with reducing the cases with pulmonary embolism.", "contents": "[Mortality rate after lung resection for bronchial carcinoma (author's transl)]. 1351 patients with lung resection were analyzed. Lethality during hospital treatment was 6.2%. 11 patients, who died during the 6 first weeks after the resection, had occult metastases. The causes of death among these 6.2% were pulmonary embolism (40.5%), insufficiency of the bronchial stump and following complications (17.9%), pneumonia (10.7%), cardiorespiratory failure (9.5%) and intraabdominal complications (8.3%). Improving these figures should begin with reducing the cases with pulmonary embolism."}
{"id": "PMID:197750", "title": "[Immunological characteristics of the 2-stage method of smallpox vaccination].", "content": "As a result of observations carried out on children the authors present immunological characteristics of two-stage smallpox vaccination at different intervals (1 to 60 days) between the injection of inactivated and live vaccine. There proved to be acceleration and intensification of antibody formation after two-stage immunization in comparison with the rutine vaccination. A seven-day interval between the injection of the inactivated and live preparations was recommended on the basis of the data obtained.", "contents": "[Immunological characteristics of the 2-stage method of smallpox vaccination]. As a result of observations carried out on children the authors present immunological characteristics of two-stage smallpox vaccination at different intervals (1 to 60 days) between the injection of inactivated and live vaccine. There proved to be acceleration and intensification of antibody formation after two-stage immunization in comparison with the rutine vaccination. A seven-day interval between the injection of the inactivated and live preparations was recommended on the basis of the data obtained."}
{"id": "PMID:197751", "title": "[Immunochemical study of the antigenic structure of microbes of the genus Bordetella. 5. Fractionation of the extracts of the parapertussis microbes and the study of the immunochemical and biochemical properties of the isolated fractions].", "content": "Fractions responsible for the main part of the serological and immunogenic activity differing by the set of antigens were isolated from the salt extracts of parapertussis microbes by gel-filtration on Sephadex G-100, ion exchange chromatography on DEAE-cellulose, and preparative electrophoresis in agar. Fractions, disclosing a sufficiently high serological activity and possessing the immunological properties, but containing the minimal set (2--3 out of 7) antigens, which were included in the initial extract, were isolated in the agar gel in the use of the preparative electrophoresis method.", "contents": "[Immunochemical study of the antigenic structure of microbes of the genus Bordetella. 5. Fractionation of the extracts of the parapertussis microbes and the study of the immunochemical and biochemical properties of the isolated fractions]. Fractions responsible for the main part of the serological and immunogenic activity differing by the set of antigens were isolated from the salt extracts of parapertussis microbes by gel-filtration on Sephadex G-100, ion exchange chromatography on DEAE-cellulose, and preparative electrophoresis in agar. Fractions, disclosing a sufficiently high serological activity and possessing the immunological properties, but containing the minimal set (2--3 out of 7) antigens, which were included in the initial extract, were isolated in the agar gel in the use of the preparative electrophoresis method."}
{"id": "PMID:197752", "title": "[Characteristics of the immunologic response of animals to Clostridium perfringens anatoxin].", "content": "Experiments were conducted on guinea pigs, rabbits and mice (mongrel and inbred); immunogenic properties of Cl. perfringens toxoids of different purity were studied. Toxin neutralization and passive hemagglutination tests were used to determine the antitoxic immunity level. It appeared that in the immunization of guinea pigs and rabbits the degree of immunogenicity of the preparations increased with the elevation of their specific activity. Under the same conditions both the mongrel and the inbred mice displayed the maximum immune response in the immunization with the least purified preparations, and the minimum after the injection of a highly purified antigen.", "contents": "[Characteristics of the immunologic response of animals to Clostridium perfringens anatoxin]. Experiments were conducted on guinea pigs, rabbits and mice (mongrel and inbred); immunogenic properties of Cl. perfringens toxoids of different purity were studied. Toxin neutralization and passive hemagglutination tests were used to determine the antitoxic immunity level. It appeared that in the immunization of guinea pigs and rabbits the degree of immunogenicity of the preparations increased with the elevation of their specific activity. Under the same conditions both the mongrel and the inbred mice displayed the maximum immune response in the immunization with the least purified preparations, and the minimum after the injection of a highly purified antigen."}
{"id": "PMID:197748", "title": "[Glucose-6-phosphatase activity of the pia mater of several representative vertebrates].", "content": "Studies have been made on the glucose-6-phosphatase activity in the pial matter of the lamprey Lampetra fluviatilis, carp Cyprinus carpio, frog Rana temporaria, tortoises Emys orbicularis and Testudo horsfieldi, hen, rabbit and cat. The data obtained not only confirmed earlier observations on extremely high activity of the enzyme in lamprey's brain, but also demonstrated high activity of glucose-6-phosphatase in the pial matter of other vertebrates, especially in tortoises.", "contents": "[Glucose-6-phosphatase activity of the pia mater of several representative vertebrates]. Studies have been made on the glucose-6-phosphatase activity in the pial matter of the lamprey Lampetra fluviatilis, carp Cyprinus carpio, frog Rana temporaria, tortoises Emys orbicularis and Testudo horsfieldi, hen, rabbit and cat. The data obtained not only confirmed earlier observations on extremely high activity of the enzyme in lamprey's brain, but also demonstrated high activity of glucose-6-phosphatase in the pial matter of other vertebrates, especially in tortoises."}
{"id": "PMID:197749", "title": "[Intracellular analysis of the effects of micro-application of several amino acids on lumbar motor neurons of Rana ridibunda frogs].", "content": "Intracellular recordings were made from lumbar motoneurones of the isolated spinal cord of the frog while glutamate, GABA or glycine were applied iontophoretically through the extracellular microelectrode. Glutamate had depolarizing excitatory effects and caused slight (if any) increase in membrane conductance. Responses to BABA and glycine were inhibitory regardless of the sign of membrane potential shift as revealed by conductance measurements and the dependence of anti- and orthodromically induced potentials on their application. Blocade of synaptic transmission by reducing extracellular Ca++ and increasing Mg++ concentrations did not alter the effects of application indicating the immediate activation of the postsynaptic membrane. These results are in agreement with the possible role of GABA and glycine as transmitters in inhibitory as transmitters in inhibitory synapses. The function of glutamate remains uncertain.", "contents": "[Intracellular analysis of the effects of micro-application of several amino acids on lumbar motor neurons of Rana ridibunda frogs]. Intracellular recordings were made from lumbar motoneurones of the isolated spinal cord of the frog while glutamate, GABA or glycine were applied iontophoretically through the extracellular microelectrode. Glutamate had depolarizing excitatory effects and caused slight (if any) increase in membrane conductance. Responses to BABA and glycine were inhibitory regardless of the sign of membrane potential shift as revealed by conductance measurements and the dependence of anti- and orthodromically induced potentials on their application. Blocade of synaptic transmission by reducing extracellular Ca++ and increasing Mg++ concentrations did not alter the effects of application indicating the immediate activation of the postsynaptic membrane. These results are in agreement with the possible role of GABA and glycine as transmitters in inhibitory as transmitters in inhibitory synapses. The function of glutamate remains uncertain."}
{"id": "PMID:197755", "title": "[Obtaining group-specific fluorescent immunoglobulin for diagnosis of adenovirus infection].", "content": "The authors present the results of a comparative study of several schemes of rabbit immunization with mixtures consisting of 4 and 7 (mixture No. 1) nad 2, 4, and 7 (mixture No. 2) adenovirus types for the purpose of obtaining group-specific fluorescent immunoglobulins. Since a direct correlative dependence of the activity of fluorescent immunoglobulins on the antibody level to the adenoviruses of homologous type was revealed in the immune sera a combined scheme of mixture No. 2 administration was elaborated for the immunization of animals.", "contents": "[Obtaining group-specific fluorescent immunoglobulin for diagnosis of adenovirus infection]. The authors present the results of a comparative study of several schemes of rabbit immunization with mixtures consisting of 4 and 7 (mixture No. 1) nad 2, 4, and 7 (mixture No. 2) adenovirus types for the purpose of obtaining group-specific fluorescent immunoglobulins. Since a direct correlative dependence of the activity of fluorescent immunoglobulins on the antibody level to the adenoviruses of homologous type was revealed in the immune sera a combined scheme of mixture No. 2 administration was elaborated for the immunization of animals."}
{"id": "PMID:197756", "title": "[Effect of thymus histones on the RNAase, ATPase and phosphatase activity of staphylococcal cells].", "content": "It was shown that the representatives of different strains of Staphylococcus genus were characterized by a differential histone sensitivity. The membrane permeability increased in case of the bacterial contact with histones, and the degrading of the sum total cell RNA occurred in the contact of bacteria with histones. The RNA-ase, phosphatase, and the ATP-ase activity increased in the cells after their treatment with histones. The extent of expression of all these processes in the representatives of different strains correlated with their sensitivity to individual histone fractions. The problem that all the phenomena described indicated both the inhibitory effect of histones and some metabolic changes (permitting the cells to preserve their viability under unfavourable conditions) is discussed.", "contents": "[Effect of thymus histones on the RNAase, ATPase and phosphatase activity of staphylococcal cells]. It was shown that the representatives of different strains of Staphylococcus genus were characterized by a differential histone sensitivity. The membrane permeability increased in case of the bacterial contact with histones, and the degrading of the sum total cell RNA occurred in the contact of bacteria with histones. The RNA-ase, phosphatase, and the ATP-ase activity increased in the cells after their treatment with histones. The extent of expression of all these processes in the representatives of different strains correlated with their sensitivity to individual histone fractions. The problem that all the phenomena described indicated both the inhibitory effect of histones and some metabolic changes (permitting the cells to preserve their viability under unfavourable conditions) is discussed."}
{"id": "PMID:197757", "title": "[Obtaining spheroplasts from the agents of glanders and melioidosis and separation of membrane structures from them].", "content": "Spheroplasts were obtained from the causative agents of glanders and melioidosis under the effect of lysozyme and antibiotics. In the capacity of an inducing agent lysozyme was effective in high concentration only (0.4%); preliminary washing and incubation in sucrose were necessary to obtain glanders spheroplasts. Of the antibiotics studied penicillin was more useful for obtaining melioidosis spheroplasts and ampicillin--for glanders spheroplasts. Membrane preparations were derived from the spheroplasts of glanders and melioidosis causative agents.", "contents": "[Obtaining spheroplasts from the agents of glanders and melioidosis and separation of membrane structures from them]. Spheroplasts were obtained from the causative agents of glanders and melioidosis under the effect of lysozyme and antibiotics. In the capacity of an inducing agent lysozyme was effective in high concentration only (0.4%); preliminary washing and incubation in sucrose were necessary to obtain glanders spheroplasts. Of the antibiotics studied penicillin was more useful for obtaining melioidosis spheroplasts and ampicillin--for glanders spheroplasts. Membrane preparations were derived from the spheroplasts of glanders and melioidosis causative agents."}
{"id": "PMID:197758", "title": "[Jugular and tympanic glomus tumors with intracranial growth].", "content": "The authors studied 9 patients with an intracranial growth of a glome tumour. Clinically it was characterized by tumorous symptoms of the middle ear or of the jugular fossa. These signs were accompanied by a cerebral hypertensive syndrome and by symptoms related to the influence of the tumour on the brain stem, cerebellum and III--IV cranial nerves. Radiotherapy was performed in 7 cases and combined therapy in 2 cases. Clinical remission in 2 patients following radiotherapy was seen during II and 3 years. After combined therapy 2 patients (during 9 and 1 year) did not demonstrate any clinical signs of tumour growth. Three patients died due to persistent growth. The fate of 2 patients is unknown.", "contents": "[Jugular and tympanic glomus tumors with intracranial growth]. The authors studied 9 patients with an intracranial growth of a glome tumour. Clinically it was characterized by tumorous symptoms of the middle ear or of the jugular fossa. These signs were accompanied by a cerebral hypertensive syndrome and by symptoms related to the influence of the tumour on the brain stem, cerebellum and III--IV cranial nerves. Radiotherapy was performed in 7 cases and combined therapy in 2 cases. Clinical remission in 2 patients following radiotherapy was seen during II and 3 years. After combined therapy 2 patients (during 9 and 1 year) did not demonstrate any clinical signs of tumour growth. Three patients died due to persistent growth. The fate of 2 patients is unknown."}
{"id": "PMID:197759", "title": "[Disorders in lipoprotein metabolism indices in cerebral atherosclerosis, their importance for diagnosis and medical-occupational expertise].", "content": "Using a wide complex of biochemical indices 166 patients with cerebral atherosclerosis were examined. It was shown that in this disease regardless of the period of acute stage a deficiency of the brain circulation of physicochemical changes of the serum proteins, lipoproteins and an oppression of the process of cholesterol exterfication precede quantitative accumulation of total cholesterol in the blood, beta-lipoproteins, a decrease of the lecethin level and changes of protein fractions. Heparin treatment along with improvement of the patients' clinical state, indices of general and brain hemodynamics decreased a free cholesterol level, increased the strength of cholesterol and apoprotein relationship and phosphorolipid content in the blood. In the author's opinion one of the leading causes of lipoprotein metabolic disorders in atherosclerosis can be a change of hormonal regulation of the activity in proteins enzymes of the organs and tissues, including the enzymes regulating an oxidation-reduction process in the organism. The significance of the studied indices for diagnosis and medical labour examination is considered.", "contents": "[Disorders in lipoprotein metabolism indices in cerebral atherosclerosis, their importance for diagnosis and medical-occupational expertise]. Using a wide complex of biochemical indices 166 patients with cerebral atherosclerosis were examined. It was shown that in this disease regardless of the period of acute stage a deficiency of the brain circulation of physicochemical changes of the serum proteins, lipoproteins and an oppression of the process of cholesterol exterfication precede quantitative accumulation of total cholesterol in the blood, beta-lipoproteins, a decrease of the lecethin level and changes of protein fractions. Heparin treatment along with improvement of the patients' clinical state, indices of general and brain hemodynamics decreased a free cholesterol level, increased the strength of cholesterol and apoprotein relationship and phosphorolipid content in the blood. In the author's opinion one of the leading causes of lipoprotein metabolic disorders in atherosclerosis can be a change of hormonal regulation of the activity in proteins enzymes of the organs and tissues, including the enzymes regulating an oxidation-reduction process in the organism. The significance of the studied indices for diagnosis and medical labour examination is considered."}
{"id": "PMID:197760", "title": "[Pathogenesis of creatinuria and aminoaciduria in neuromuscular diseases].", "content": "By introducing inhibitors of phosphodiestherase and adenylacyclase the authors studied the role of cyclic AMP in the pathogenesis of creatinuria and aminoaciduria in neuro-muscular diseases. It was demonstrated that in patients with Duchenne myopathy creatinuria and aminoaciduria were possibly due to a deop of nucleotide level in the muscles. And on the contrary in cases of Erb's and Landouzy-Dejerine myopathy the changes of nitrogen metabolism are due to an increased content of cyclic AMP. These data may be used for differential diagnosis of myopathy.", "contents": "[Pathogenesis of creatinuria and aminoaciduria in neuromuscular diseases]. By introducing inhibitors of phosphodiestherase and adenylacyclase the authors studied the role of cyclic AMP in the pathogenesis of creatinuria and aminoaciduria in neuro-muscular diseases. It was demonstrated that in patients with Duchenne myopathy creatinuria and aminoaciduria were possibly due to a deop of nucleotide level in the muscles. And on the contrary in cases of Erb's and Landouzy-Dejerine myopathy the changes of nitrogen metabolism are due to an increased content of cyclic AMP. These data may be used for differential diagnosis of myopathy."}
{"id": "PMID:197761", "title": "[Electron-cytochemical study of nervous tissue at different periods after death].", "content": "Using electron cytochemistry the authors studied the brain frontal cortex and hypothalamus in rats and humans in different periods following death. With the aid of 3,3'-diaminobenzidin, cytochrome C which was located inside the crystal and between the external and internal membrane of the mitochondria was detected. ATP-ase and acid phosphatase was revealed by the lead method. The activity of acid phosphotase was demonstrated in the nucleoli, along the membrane of the cytoplasmatical reticulum, in the symaptical terminals and in the circulatory capillaries. It was established that in the human brain it is possible to study the localization of the cytochrome C up to 24 hours, ATP-ase up to 15-20 hours and acid phosphatase up to 12 hours following death.", "contents": "[Electron-cytochemical study of nervous tissue at different periods after death]. Using electron cytochemistry the authors studied the brain frontal cortex and hypothalamus in rats and humans in different periods following death. With the aid of 3,3'-diaminobenzidin, cytochrome C which was located inside the crystal and between the external and internal membrane of the mitochondria was detected. ATP-ase and acid phosphatase was revealed by the lead method. The activity of acid phosphotase was demonstrated in the nucleoli, along the membrane of the cytoplasmatical reticulum, in the symaptical terminals and in the circulatory capillaries. It was established that in the human brain it is possible to study the localization of the cytochrome C up to 24 hours, ATP-ase up to 15-20 hours and acid phosphatase up to 12 hours following death."}
{"id": "PMID:197763", "title": "Pituitary adrenal system hormones and behaviour.", "content": "Neuropeptides related to ACTH, MSH and LPH are involved in acquisition and maintenance of conditioned behaviour. These peptides affect the behaviour by a temporary selective increase in the state of arousal in limbic midbrain structures, thereby increasing the motivational influence of environmental stimuli. Steroids of adrenal origin affect conditioned behaviour in a way opposite to that of ACTH and related peptides. Such steroids alter the arousal level in limbic midbrain structures to enhance discrimination and consequently the elimination of non relevant behaviourla responses. Neuropeptides related to ACTH play a basic role in motivational, learning and memory processes, while the pituitary-adrenal system through the secretion of corticosteroids has a secondary modulationg function.", "contents": "Pituitary adrenal system hormones and behaviour. Neuropeptides related to ACTH, MSH and LPH are involved in acquisition and maintenance of conditioned behaviour. These peptides affect the behaviour by a temporary selective increase in the state of arousal in limbic midbrain structures, thereby increasing the motivational influence of environmental stimuli. Steroids of adrenal origin affect conditioned behaviour in a way opposite to that of ACTH and related peptides. Such steroids alter the arousal level in limbic midbrain structures to enhance discrimination and consequently the elimination of non relevant behaviourla responses. Neuropeptides related to ACTH play a basic role in motivational, learning and memory processes, while the pituitary-adrenal system through the secretion of corticosteroids has a secondary modulationg function."}
{"id": "PMID:197764", "title": "Histochemical features of C-cell thyroid carcinoma.", "content": "Six cases of C-cell carcinoma of thyroid gland were studied applying histologic and histochemical methods as well as electron microscopy technique. A histologic feature of the carcinoma pattern was the diversity of pictures. Amyloid was commonly found in the carcinoma stroma. In some cells glycogen was present. Histochemically the carcinoma cells were marked by a strong activity of oxidative enzymes (GDH, SDH, LDH and MAO) as well as hydrolitic one (G-6-P and non specific enterases). Serotonin was found in two cases. An ultrastructural feature of carcinoma cells was the presence of cytoplasmic electron-dense, specific \"endocrine type\" secretory granules.", "contents": "Histochemical features of C-cell thyroid carcinoma. Six cases of C-cell carcinoma of thyroid gland were studied applying histologic and histochemical methods as well as electron microscopy technique. A histologic feature of the carcinoma pattern was the diversity of pictures. Amyloid was commonly found in the carcinoma stroma. In some cells glycogen was present. Histochemically the carcinoma cells were marked by a strong activity of oxidative enzymes (GDH, SDH, LDH and MAO) as well as hydrolitic one (G-6-P and non specific enterases). Serotonin was found in two cases. An ultrastructural feature of carcinoma cells was the presence of cytoplasmic electron-dense, specific \"endocrine type\" secretory granules."}
{"id": "PMID:197767", "title": "Antibodies against herpes simplex virus type 1 subunit antigens in patients with trigeminal neuralgia and controls.", "content": "Serum IgG antibody levels against herpes simplex virus (HSV) type 1 subunit (capsid, envelope, and excreted) antigens detected with radioimmunoassay were compared in 25 patients with trigeminal neuralgia and their age- and sex-matched controls. No significant differences were found between the patients and controls, either in the distribution of the antibody titers or in the mean titers against any of the subunit antigens tested. In 6 patients HSV antibody titers were tested before and after trigeminal root section; no significant changes were observed.", "contents": "Antibodies against herpes simplex virus type 1 subunit antigens in patients with trigeminal neuralgia and controls. Serum IgG antibody levels against herpes simplex virus (HSV) type 1 subunit (capsid, envelope, and excreted) antigens detected with radioimmunoassay were compared in 25 patients with trigeminal neuralgia and their age- and sex-matched controls. No significant differences were found between the patients and controls, either in the distribution of the antibody titers or in the mean titers against any of the subunit antigens tested. In 6 patients HSV antibody titers were tested before and after trigeminal root section; no significant changes were observed."}
{"id": "PMID:197769", "title": "Characteristic residual neuropathological features of Japanese B encephalitis.", "content": "Characteristic residual (12-67 years) neuropathological features of 4 verified or suspected cases of Japanese B encephalitis (JBE) are reported. These features are summarized as: 1. unique distribution pattern of the main lesions, i.e. combination of lesions in the thalamus, substantia nigra and Ammon's horn. Lesions in the thalamus consistently involved, in a linear fashion, lamina medullaris medialis with nucleus intralaminalis and adjacent portions of the nucleus lateralis thalami. Lesions in the substantia nigra usually occupied the middle parts of zona compacta. These lesions were usually symmetrical, though unequal in extent. 2. Unique nature of the lesions, especially those in the thalamus and substantia nigra. Characteristic \"light circumscribed foci (LCF)\", which consisted of small rarefied areas, with few cellular and fibrous elements, surrounded by dense gliomesenchymal scarring, were observed there and occasionally in cerebral cortices. Lesions were thought to be vestiges of \"circumscribed necrotic foci\" reported in the CNS of acute stage of JBE. Additional characteristic features in the thalamic lesions were calcified and binucleated nerve cells. Alzheimer's neurofibrillary tangles were not found. Authors consider that the distribution and nature of the lesions are of diagnostic value.", "contents": "Characteristic residual neuropathological features of Japanese B encephalitis. Characteristic residual (12-67 years) neuropathological features of 4 verified or suspected cases of Japanese B encephalitis (JBE) are reported. These features are summarized as: 1. unique distribution pattern of the main lesions, i.e. combination of lesions in the thalamus, substantia nigra and Ammon's horn. Lesions in the thalamus consistently involved, in a linear fashion, lamina medullaris medialis with nucleus intralaminalis and adjacent portions of the nucleus lateralis thalami. Lesions in the substantia nigra usually occupied the middle parts of zona compacta. These lesions were usually symmetrical, though unequal in extent. 2. Unique nature of the lesions, especially those in the thalamus and substantia nigra. Characteristic \"light circumscribed foci (LCF)\", which consisted of small rarefied areas, with few cellular and fibrous elements, surrounded by dense gliomesenchymal scarring, were observed there and occasionally in cerebral cortices. Lesions were thought to be vestiges of \"circumscribed necrotic foci\" reported in the CNS of acute stage of JBE. Additional characteristic features in the thalamic lesions were calcified and binucleated nerve cells. Alzheimer's neurofibrillary tangles were not found. Authors consider that the distribution and nature of the lesions are of diagnostic value."}
{"id": "PMID:197770", "title": "Ultrastructure of muscle and sensory nerve in Fabry's disease.", "content": "A study of a muscle biopsy has provided evidence of storage involvement of the skeletal muscle fibres in Fabry's disease. In the endothelial cells of the capillaries, the inclusions were more abundant and pleomorphic. Muscle satellite cells were spared. In the sensory nerve biopsy, the perineurial and endothelial cells contained lamillar bodies, but not the Schwann cells. There was a slight reduction of the number of the small myelinated fibres and of the unmyelinated fibres. An electron microscopic study of a muscle biopsy can be helpful in the diagnosis of the disease. The physiopathology of the pain attacks is still a matter for discussion.", "contents": "Ultrastructure of muscle and sensory nerve in Fabry's disease. A study of a muscle biopsy has provided evidence of storage involvement of the skeletal muscle fibres in Fabry's disease. In the endothelial cells of the capillaries, the inclusions were more abundant and pleomorphic. Muscle satellite cells were spared. In the sensory nerve biopsy, the perineurial and endothelial cells contained lamillar bodies, but not the Schwann cells. There was a slight reduction of the number of the small myelinated fibres and of the unmyelinated fibres. An electron microscopic study of a muscle biopsy can be helpful in the diagnosis of the disease. The physiopathology of the pain attacks is still a matter for discussion."}
{"id": "PMID:197771", "title": "Anterior horn cell degeneration and Bunina-type inclusions associated with dementia.", "content": "The ultrastructural features of Bunina type inclusions in the anterior horn cells of a patient dying of amyotrophic lateral sclerosis with dementia appear unique. The Bunina-type inclusions are electron dense aggregates containing, and surrounded by organelle-like membranes. These inclusions appear to be a special type of autophagic vacuole, possibly arising from altered mitochondria.", "contents": "Anterior horn cell degeneration and Bunina-type inclusions associated with dementia. The ultrastructural features of Bunina type inclusions in the anterior horn cells of a patient dying of amyotrophic lateral sclerosis with dementia appear unique. The Bunina-type inclusions are electron dense aggregates containing, and surrounded by organelle-like membranes. These inclusions appear to be a special type of autophagic vacuole, possibly arising from altered mitochondria."}
{"id": "PMID:197772", "title": "Acid hydrolase and cytochrome oxidase activities in nitrosourea induced tumors of the nervous system.", "content": "Nitrosourea induced tumors of the nervous system in rats have proven useful for biochemical studies combined with morphological approaches. The pattern of enzyme activities for acid hydrolases and cytochrome oxidase resemble those previously observed in spontaneous nervous system tumors of man. The activities of 4 acid hydrolases were generally high in the gliomas. This could not be attributed solely to zones of regression or necrosis but was a general characteristic of the neoplasms. The activities were predominantly particulate and most likely lysosomal in localization. In schwannomas a similar increase in hydrolases was found in comparison with normal neural tissues but aryl-sulfatase was not increased. Cytochrome oxidase activities were markedly reduced in all tumors studied. The proportionate reduction with respect to normal brain was comparable to that noted in man. No differences were found with respect to fairly well differentiated gliomas.", "contents": "Acid hydrolase and cytochrome oxidase activities in nitrosourea induced tumors of the nervous system. Nitrosourea induced tumors of the nervous system in rats have proven useful for biochemical studies combined with morphological approaches. The pattern of enzyme activities for acid hydrolases and cytochrome oxidase resemble those previously observed in spontaneous nervous system tumors of man. The activities of 4 acid hydrolases were generally high in the gliomas. This could not be attributed solely to zones of regression or necrosis but was a general characteristic of the neoplasms. The activities were predominantly particulate and most likely lysosomal in localization. In schwannomas a similar increase in hydrolases was found in comparison with normal neural tissues but aryl-sulfatase was not increased. Cytochrome oxidase activities were markedly reduced in all tumors studied. The proportionate reduction with respect to normal brain was comparable to that noted in man. No differences were found with respect to fairly well differentiated gliomas."}
{"id": "PMID:197773", "title": "An adult case of canine neuronal ceroid-lipofuscinosis.", "content": "Intraneuronal accumulation of cytosomes with the fluorescent and tinctorial properties of ceroidlipofuscin occurred in the C.N.S. of a fully matured dog with signs of slowly progressive cerebellar disease. Ultrastructural study revealed various membrane-bound inclusions in addition to typical lipofuscin granules. The clinicopathologic findings in this case were contrasted with those occurring in English Setters with juvenile neuronal ceroid-lipofuscinosis, and compared with those reported in Kufs' disease in man.", "contents": "An adult case of canine neuronal ceroid-lipofuscinosis. Intraneuronal accumulation of cytosomes with the fluorescent and tinctorial properties of ceroidlipofuscin occurred in the C.N.S. of a fully matured dog with signs of slowly progressive cerebellar disease. Ultrastructural study revealed various membrane-bound inclusions in addition to typical lipofuscin granules. The clinicopathologic findings in this case were contrasted with those occurring in English Setters with juvenile neuronal ceroid-lipofuscinosis, and compared with those reported in Kufs' disease in man."}
{"id": "PMID:197774", "title": "Radiation-induced nerve root degeneration and hypertrophic neuropathy in the lumbosacral spinal cord of rats: the relation with changes in aging rats.", "content": "Three-month-old WAG/Rij rats were irradiated with 300 kV X-rays on the lumbar region of the spinal column with doses below the level for causing paralysis due to radiation radiculomyelopathy. 8--9 months after irradiation, degeneration of predominantly the ventral nerve roots of the cauda equina was boserved. Three stages were distinguishable: I) Demyelination and proliferation of Schwann cells; II) Local swelling of ventral nerve roots, with concentric layers of Schwann cells resembling hypertrophic neuropathy; III) Malignant Schwannoma, invading roots and spinal cord. It is concluded that the degenerative and proliferative lesions represent a continuous series of stages of slowly progressive lesions. The ventral nerve root degeneration (1st stage) is similar to that observed in aging, unirradiated rats, normally developing at the age of 18--20 months.", "contents": "Radiation-induced nerve root degeneration and hypertrophic neuropathy in the lumbosacral spinal cord of rats: the relation with changes in aging rats. Three-month-old WAG/Rij rats were irradiated with 300 kV X-rays on the lumbar region of the spinal column with doses below the level for causing paralysis due to radiation radiculomyelopathy. 8--9 months after irradiation, degeneration of predominantly the ventral nerve roots of the cauda equina was boserved. Three stages were distinguishable: I) Demyelination and proliferation of Schwann cells; II) Local swelling of ventral nerve roots, with concentric layers of Schwann cells resembling hypertrophic neuropathy; III) Malignant Schwannoma, invading roots and spinal cord. It is concluded that the degenerative and proliferative lesions represent a continuous series of stages of slowly progressive lesions. The ventral nerve root degeneration (1st stage) is similar to that observed in aging, unirradiated rats, normally developing at the age of 18--20 months."}
{"id": "PMID:197775", "title": "Dense core vesicles around the Lewy body in incidental Parkinson's disease: an electron microscopic study.", "content": "In a case of Lewy body disease incidentally found at autopsy, numerous dense core vesicles 80--200 nm in diameter, were seen in the neuronal perikarya of the locus caeruleus. They were particularly numerous in the vicinity of the Lewy bodies. The change seems to occur at the early stage of Lewy body production and may represent an additional morphologic clue to abnormal catecholamine metabolism in Parkinson's disease.", "contents": "Dense core vesicles around the Lewy body in incidental Parkinson's disease: an electron microscopic study. In a case of Lewy body disease incidentally found at autopsy, numerous dense core vesicles 80--200 nm in diameter, were seen in the neuronal perikarya of the locus caeruleus. They were particularly numerous in the vicinity of the Lewy bodies. The change seems to occur at the early stage of Lewy body production and may represent an additional morphologic clue to abnormal catecholamine metabolism in Parkinson's disease."}
{"id": "PMID:197776", "title": "Infection of cultivated CNS tissue with herpes virus, HSVII. A reappraisal.", "content": "Organized cultures of newborn rat and hamster cerebellum were infected with herpes virus type II, after 7 and 14 days \"in vitro\". 48 h after the infection, electron microscopic examination of the cultures showed that astrocytes contained numerous intranuclear and intracytoplasmic viral particles, while neurons remained apparently intact. The specificity of the infection for a given cell type is discussed.", "contents": "Infection of cultivated CNS tissue with herpes virus, HSVII. A reappraisal. Organized cultures of newborn rat and hamster cerebellum were infected with herpes virus type II, after 7 and 14 days \"in vitro\". 48 h after the infection, electron microscopic examination of the cultures showed that astrocytes contained numerous intranuclear and intracytoplasmic viral particles, while neurons remained apparently intact. The specificity of the infection for a given cell type is discussed."}
{"id": "PMID:197778", "title": "Carbamyl-phosphate-synthetase deficiency with neonatal onset of symptoms.", "content": "The clinical course and biochemical findings in a case of carbamyl-phosphate-synthetase deficiency are described. The patient, a boy, presented 48 h after birth with rapidly developing hypotonia and hypothermia. Pulmonary haemorrhage, melaena and haematemesis ensued and despite ventilatory assistance and peritoneal dialysis the patient died on the fifth day. A virtual absence of carbamyl phosphate synthetase I (N-acetylglutamate dependent) was proved by analysis of tissue samples removed post mortem. Other urea cycle enzymes were normal.", "contents": "Carbamyl-phosphate-synthetase deficiency with neonatal onset of symptoms. The clinical course and biochemical findings in a case of carbamyl-phosphate-synthetase deficiency are described. The patient, a boy, presented 48 h after birth with rapidly developing hypotonia and hypothermia. Pulmonary haemorrhage, melaena and haematemesis ensued and despite ventilatory assistance and peritoneal dialysis the patient died on the fifth day. A virtual absence of carbamyl phosphate synthetase I (N-acetylglutamate dependent) was proved by analysis of tissue samples removed post mortem. Other urea cycle enzymes were normal."}
{"id": "PMID:197779", "title": "Oculodentodigital dysplasia syndrome. Report of four cases.", "content": "Four cases of oculodentodigital dysplasia are reported. Three cases are from the same family, father and two daughers. These three cases have the characteristics typical of this disorder: narrow nose, hypoplastic alae nasi, microphthalmia, defects of the teeth, syndactylyl of the IV and V fingers, and skeletal anomalies. The fourth case differs from the earlier reported cases; he has all the typical findings of oculodentodigital dysplasia but in addition he shows features not previously reported, namely exceptionally poor vision, mental retardation, monilethrix and pili annuli changes of the hair.", "contents": "Oculodentodigital dysplasia syndrome. Report of four cases. Four cases of oculodentodigital dysplasia are reported. Three cases are from the same family, father and two daughers. These three cases have the characteristics typical of this disorder: narrow nose, hypoplastic alae nasi, microphthalmia, defects of the teeth, syndactylyl of the IV and V fingers, and skeletal anomalies. The fourth case differs from the earlier reported cases; he has all the typical findings of oculodentodigital dysplasia but in addition he shows features not previously reported, namely exceptionally poor vision, mental retardation, monilethrix and pili annuli changes of the hair."}
{"id": "PMID:197780", "title": "Primary carcinoma of the liver. A histological study of 27 cases of primary carcinoma of the liver from Malawi.", "content": "Liver biopsies from 27 Bantu patients with primary carcinoma of the liver from Malawi were examined histologically. All the biopsies showed hepatocellular carcinoma (HCC). Structurally the tumours consisted of trabeculae or groups of such, separated by a variable amount of connective tissue which in a few cases was so pronounced that the tumour had a scirrhous character. Evaluation of the grade of differentiation showed 3 cases to be of grade I, 10 of grade II, 5 of grade III, and 8 of grade IV. The grade could bary in tumour tissue from the same patient, but never extremely so. The histological structure did not differ significantly from that found in other African and Caucasian series. The reticulin structure of tumour tissue was found distinctly different from that of benign tissue and thus an important tool in the differential diagnosis between HCC grade I and normal or cirrhotic liver tissue. Out of 15 patients 12 had cirrhosis which was of the postnecrotic type.", "contents": "Primary carcinoma of the liver. A histological study of 27 cases of primary carcinoma of the liver from Malawi. Liver biopsies from 27 Bantu patients with primary carcinoma of the liver from Malawi were examined histologically. All the biopsies showed hepatocellular carcinoma (HCC). Structurally the tumours consisted of trabeculae or groups of such, separated by a variable amount of connective tissue which in a few cases was so pronounced that the tumour had a scirrhous character. Evaluation of the grade of differentiation showed 3 cases to be of grade I, 10 of grade II, 5 of grade III, and 8 of grade IV. The grade could bary in tumour tissue from the same patient, but never extremely so. The histological structure did not differ significantly from that found in other African and Caucasian series. The reticulin structure of tumour tissue was found distinctly different from that of benign tissue and thus an important tool in the differential diagnosis between HCC grade I and normal or cirrhotic liver tissue. Out of 15 patients 12 had cirrhosis which was of the postnecrotic type."}
{"id": "PMID:197781", "title": "Scanning electron microscopic surface morphology of isolated hepatocytes from normal and premalignant rat liver.", "content": "Scanning electron microscopy was performed on hepatocytes isolated after collagenase perfusion of livers from rats fed 2-acetylaminofluorene (AAF) in the diet for 6--8 weeks and on hepatocytes from control rats. The premalignant AAF-cells showed a greater variation in cell size and shape. They also exhibited a reduced number of microvilli and more blebs and other protrusions on the surface than hepatocytes from control animals.", "contents": "Scanning electron microscopic surface morphology of isolated hepatocytes from normal and premalignant rat liver. Scanning electron microscopy was performed on hepatocytes isolated after collagenase perfusion of livers from rats fed 2-acetylaminofluorene (AAF) in the diet for 6--8 weeks and on hepatocytes from control rats. The premalignant AAF-cells showed a greater variation in cell size and shape. They also exhibited a reduced number of microvilli and more blebs and other protrusions on the surface than hepatocytes from control animals."}
{"id": "PMID:197782", "title": "Gastric carcinoma I. The reproducibility of a histogenetic classification proposed by Masson, Rember and Mulligan.", "content": "The purpose of the present paper has been to examine the reproducibility of the classification of gastric carcinomas, as proposed by Mulligan and Rember. Two microscopic slides from each of one hundred randomly selected specimens of gastric carcinoma, obtained by gastrectomy or gastric resection, were classified independently by both authors. Neither of the authors knew which slides originated from the same specimen. The inter-examiner reproducibility rate was 79 per cent. The reproducibility rates of the diagnoses with two independent slides from the same tumour was 74 per cent with examiner I and 80 per cent with examiner II.", "contents": "Gastric carcinoma I. The reproducibility of a histogenetic classification proposed by Masson, Rember and Mulligan. The purpose of the present paper has been to examine the reproducibility of the classification of gastric carcinomas, as proposed by Mulligan and Rember. Two microscopic slides from each of one hundred randomly selected specimens of gastric carcinoma, obtained by gastrectomy or gastric resection, were classified independently by both authors. Neither of the authors knew which slides originated from the same specimen. The inter-examiner reproducibility rate was 79 per cent. The reproducibility rates of the diagnoses with two independent slides from the same tumour was 74 per cent with examiner I and 80 per cent with examiner II."}
{"id": "PMID:197783", "title": "Gastric carcinoma 2. An analysis of morphological and prognostic parameters correlated to the classification proposed by Masson, Rember and Mulligan.", "content": "One-hundred and fifteen gastric adenocarcinomas were classified according to Mulligan and Rember into one of the following types: Intestinal cell carcinoma (IC), pyloro-cardiac gland carcinoma (PC), mucous cell carcinoma (MC) and unclassified. The tumour type was correlated to the growth pattern and inflammatory reaction at the margin of the tumour, invasion of the veins and nerve sheaths, Dukes' stage, intra- and extracellular mucous production, and occurrence of intestinal metaplasia in the non-tumour bearing parts of the gastric mucosa. MC was the only type of tumour producing the macroscopic picture \"linitis plastica\". PC was the type of tumour that dominated in the cardiac region. The following parameters showed no relation to tumour type: Sex and age, size of tumour, invasion of lymphatic vessels. This study suggests that the three types of tumour are different entities, MC being the most aggressive and IC the least aggressive of the types of tumour.", "contents": "Gastric carcinoma 2. An analysis of morphological and prognostic parameters correlated to the classification proposed by Masson, Rember and Mulligan. One-hundred and fifteen gastric adenocarcinomas were classified according to Mulligan and Rember into one of the following types: Intestinal cell carcinoma (IC), pyloro-cardiac gland carcinoma (PC), mucous cell carcinoma (MC) and unclassified. The tumour type was correlated to the growth pattern and inflammatory reaction at the margin of the tumour, invasion of the veins and nerve sheaths, Dukes' stage, intra- and extracellular mucous production, and occurrence of intestinal metaplasia in the non-tumour bearing parts of the gastric mucosa. MC was the only type of tumour producing the macroscopic picture \"linitis plastica\". PC was the type of tumour that dominated in the cardiac region. The following parameters showed no relation to tumour type: Sex and age, size of tumour, invasion of lymphatic vessels. This study suggests that the three types of tumour are different entities, MC being the most aggressive and IC the least aggressive of the types of tumour."}
{"id": "PMID:197784", "title": "Cytochemical electron microscopy on polysaccharide granules in the endogenous forms of Eimeria brunetti.", "content": "The endogenous stages in the life cycle of Eimeria brunetti were tested for polysaccharide material by electron microscopical cytochemistry using the periodic acid-thiocarbohydrazide-osmium tetroxide (PATO)-method. The parasites were observed within the epithelial cells of the small intestine of infected domestic fowls. Two types of granules reacted positively for polysaccharide. The first was large, approximately 500 nm by 250 nm. These granules had an appearance similar to the polysaccharide granules reported for other coccidian parasites. They were observed in mature merozoites, macrogamonts, and developing oocysts. The second type of granule was smaller (15-30 nm in diameter) and was only observed at the periphery of the residual cytoplasmic mass of mature microgamonts. It was more similar in appearance to metazoan glycogen than the former. However, since the PATO-method does not differentiate between different polysaccharides it can not be proven if these granules in fast contain glycogen. The WFBI of the macrogamete and the outer layer of the oocyst wall gave a slight positive reaction but after examination of the controls it appeared that this was not a specific reaction for polysaccharides.", "contents": "Cytochemical electron microscopy on polysaccharide granules in the endogenous forms of Eimeria brunetti. The endogenous stages in the life cycle of Eimeria brunetti were tested for polysaccharide material by electron microscopical cytochemistry using the periodic acid-thiocarbohydrazide-osmium tetroxide (PATO)-method. The parasites were observed within the epithelial cells of the small intestine of infected domestic fowls. Two types of granules reacted positively for polysaccharide. The first was large, approximately 500 nm by 250 nm. These granules had an appearance similar to the polysaccharide granules reported for other coccidian parasites. They were observed in mature merozoites, macrogamonts, and developing oocysts. The second type of granule was smaller (15-30 nm in diameter) and was only observed at the periphery of the residual cytoplasmic mass of mature microgamonts. It was more similar in appearance to metazoan glycogen than the former. However, since the PATO-method does not differentiate between different polysaccharides it can not be proven if these granules in fast contain glycogen. The WFBI of the macrogamete and the outer layer of the oocyst wall gave a slight positive reaction but after examination of the controls it appeared that this was not a specific reaction for polysaccharides."}
{"id": "PMID:197785", "title": "Thermostable Neisseria gonorrhoeae antigens examined by a bacterial agglutination test.", "content": "Rabbit antisera against three different N. gonorrhoeae isolates agglutinated heated gonococci (100 degrees C, 2 h) before and after treatment with periodate or pronase, but this was not the case with gonococci exposed to the combined action of the reagents. All agglutinins could be removed by absorption of antiserum with untreated or heat-treated gonococci or with a heat extract of the bacteria. Antiserum absorbed with the lipopolysaccharide still agglutinated the heated gonococci both before and after exposure of the bacteria to periodate or pronase. The results of cross-absorption experiments indicated strain variation of thermostable antigenic determinants involved in the agglutination reaction.", "contents": "Thermostable Neisseria gonorrhoeae antigens examined by a bacterial agglutination test. Rabbit antisera against three different N. gonorrhoeae isolates agglutinated heated gonococci (100 degrees C, 2 h) before and after treatment with periodate or pronase, but this was not the case with gonococci exposed to the combined action of the reagents. All agglutinins could be removed by absorption of antiserum with untreated or heat-treated gonococci or with a heat extract of the bacteria. Antiserum absorbed with the lipopolysaccharide still agglutinated the heated gonococci both before and after exposure of the bacteria to periodate or pronase. The results of cross-absorption experiments indicated strain variation of thermostable antigenic determinants involved in the agglutination reaction."}
{"id": "PMID:197786", "title": "Studies on the mechanism of flush induced by nicotinic acid.", "content": "Flush is a common side effect of nicotinic acid therapy in patients. The effect is present as long as the level of nicotinic acid increases in the plasma. The mechanism of flush after nicotinic acid has been studied in the ears of guinea-pigs in vivo. The threshold dose of nicotinic acid (1-3 mg/kg) to raise the skin temperature of the ears and to increase the cyclic AMP level of this tissue was similar. Indomethacin and acetylsalicylic acid which inhibit the synthesis of prostaglandins markedly reduce the duration and intensity of the flush. In isolated slices from guinea-pig ears, nicotinic acid increased the level of cyclic AMP; this effect was inhibited by indomethacin. The stimulating action of prostaglandin E1 on the cyclic AMP level of the ear slices was not inhibited by indomethacin. Since administration to man of both cyclic AMP and prostaglandin E1 produces flush it is suggested that nicotinic acid may induce flush by the formation of some prostaglandin which then increases the formation of cyclic AMP.", "contents": "Studies on the mechanism of flush induced by nicotinic acid. Flush is a common side effect of nicotinic acid therapy in patients. The effect is present as long as the level of nicotinic acid increases in the plasma. The mechanism of flush after nicotinic acid has been studied in the ears of guinea-pigs in vivo. The threshold dose of nicotinic acid (1-3 mg/kg) to raise the skin temperature of the ears and to increase the cyclic AMP level of this tissue was similar. Indomethacin and acetylsalicylic acid which inhibit the synthesis of prostaglandins markedly reduce the duration and intensity of the flush. In isolated slices from guinea-pig ears, nicotinic acid increased the level of cyclic AMP; this effect was inhibited by indomethacin. The stimulating action of prostaglandin E1 on the cyclic AMP level of the ear slices was not inhibited by indomethacin. Since administration to man of both cyclic AMP and prostaglandin E1 produces flush it is suggested that nicotinic acid may induce flush by the formation of some prostaglandin which then increases the formation of cyclic AMP."}
{"id": "PMID:197787", "title": "Cyclic AMP and Ca-binding in microsomal fractions isolated from rabbit colon smooth muscle.", "content": "From a homogenate of rabbit colon muscle two ATP dependent Ca-accumulating microsomal fractions were isolated by differential centrifugation on a sucrose density grandient at 35% and 35-45% sucrose. Adenylate cyclase and phosphodiesterase activities were found in the fractions. The Ca-accumulation and the ATPase activity of these fractions were stimulated by cyclic AMP (10(-5)M) at an ATP concentration of 0.35 mM ATP. In the presence of higher concentrations of ATP (5 mM) cyclic AMP had no effect on the Ca-binding. The higher concentration of ATP markedly increased the cyclic AMP formation in relation to the activity found at the lower concentration of ATP. Isoprenaline (2 X 10(-6)M) stimulated the Ca-accumulation in the 35-45% fraction and increased the hydrolysis of ATP. These effects were absent in the fraction isolated at 35% sucrose. In the former fraction isoprenaline also stimulated the adenylate cyclase activity at 0.35 mM but not at 5 mM ATP. Both the effect of isoprenaline on the Ca-binding and the adenylate cyclase activity were inhibited by the adrenergic beta-receptor blocking agent sotalol. In the 35-45% fraction papaverine (1 X 10(-3)M) stimulated the Ca-accumulation and inhibited the phosphodiesterase activity. It is suggested that cyclic AMP and agents which influence the cyclic AMP metabolism in the microsomes may have a regulatory role on the Ca-binding of the microsomes.", "contents": "Cyclic AMP and Ca-binding in microsomal fractions isolated from rabbit colon smooth muscle. From a homogenate of rabbit colon muscle two ATP dependent Ca-accumulating microsomal fractions were isolated by differential centrifugation on a sucrose density grandient at 35% and 35-45% sucrose. Adenylate cyclase and phosphodiesterase activities were found in the fractions. The Ca-accumulation and the ATPase activity of these fractions were stimulated by cyclic AMP (10(-5)M) at an ATP concentration of 0.35 mM ATP. In the presence of higher concentrations of ATP (5 mM) cyclic AMP had no effect on the Ca-binding. The higher concentration of ATP markedly increased the cyclic AMP formation in relation to the activity found at the lower concentration of ATP. Isoprenaline (2 X 10(-6)M) stimulated the Ca-accumulation in the 35-45% fraction and increased the hydrolysis of ATP. These effects were absent in the fraction isolated at 35% sucrose. In the former fraction isoprenaline also stimulated the adenylate cyclase activity at 0.35 mM but not at 5 mM ATP. Both the effect of isoprenaline on the Ca-binding and the adenylate cyclase activity were inhibited by the adrenergic beta-receptor blocking agent sotalol. In the 35-45% fraction papaverine (1 X 10(-3)M) stimulated the Ca-accumulation and inhibited the phosphodiesterase activity. It is suggested that cyclic AMP and agents which influence the cyclic AMP metabolism in the microsomes may have a regulatory role on the Ca-binding of the microsomes."}
{"id": "PMID:197791", "title": "Studies on the phosphodiesterase in various organs of rats and guinea-pigs of different ages and different sex.", "content": "The method of Butcher and Sutherland is used to determine the phosphodiesterase activity of various organ homogenates from rats and guinea-pigs of different age and sex. The different rat organs manifest great differences in their phosphodiesterase activity. Especially high phosphodiesterase activity is found in the adrenal gland and in the brain cortex. Sex is not found to be related to definite differences in the activity of the enzyme. In some organs age differences are established both in the phosphodiesterase activity and in the degree of its inhibition or activation by inhibitors and stimulators of the enzyme. It is assumed that in some organs age conditions changes not only in the general phosphodiesterase activity, but also in the ratio between its isoenzymes.", "contents": "Studies on the phosphodiesterase in various organs of rats and guinea-pigs of different ages and different sex. The method of Butcher and Sutherland is used to determine the phosphodiesterase activity of various organ homogenates from rats and guinea-pigs of different age and sex. The different rat organs manifest great differences in their phosphodiesterase activity. Especially high phosphodiesterase activity is found in the adrenal gland and in the brain cortex. Sex is not found to be related to definite differences in the activity of the enzyme. In some organs age differences are established both in the phosphodiesterase activity and in the degree of its inhibition or activation by inhibitors and stimulators of the enzyme. It is assumed that in some organs age conditions changes not only in the general phosphodiesterase activity, but also in the ratio between its isoenzymes."}
{"id": "PMID:197794", "title": "Effects of volleys in cortico-spinal tract fibres on ventral spino-cerebellar tract cells in the cat.", "content": "Both excitation and inhibition has been found in cells of origin of the ventral spino-cerebellar tract (VSCT) to be evoked by volleys in cortico-spinal fibres. The earliest EPSPs and IPSPs had features of disynaptically evoked postsynaptic potentials; these were, however, found only in a small proportion of cells and polysynaptic EPSPs and IPSPs were dominating . Postsynaptic potentials evoked in VSCT cells from primary afferents were effectively facilitated by cortico-spinal volleys. The cortico-spinal effects on VSCT cells may thus well be mediated by the same interneurones which mediate their excitation or inhibition from the periphery and which could evoke similar postsynaptic potentials in motoneurones. Generally all the observation are in keeping with the hypothesis (Lundberg 1971) that VSCT cells monitor transmission through interneurones interposed in various reflex paths to motoneurones.", "contents": "Effects of volleys in cortico-spinal tract fibres on ventral spino-cerebellar tract cells in the cat. Both excitation and inhibition has been found in cells of origin of the ventral spino-cerebellar tract (VSCT) to be evoked by volleys in cortico-spinal fibres. The earliest EPSPs and IPSPs had features of disynaptically evoked postsynaptic potentials; these were, however, found only in a small proportion of cells and polysynaptic EPSPs and IPSPs were dominating . Postsynaptic potentials evoked in VSCT cells from primary afferents were effectively facilitated by cortico-spinal volleys. The cortico-spinal effects on VSCT cells may thus well be mediated by the same interneurones which mediate their excitation or inhibition from the periphery and which could evoke similar postsynaptic potentials in motoneurones. Generally all the observation are in keeping with the hypothesis (Lundberg 1971) that VSCT cells monitor transmission through interneurones interposed in various reflex paths to motoneurones."}
{"id": "PMID:197795", "title": "Sleep and behavioral changes possibly reflecting central receptor hypersensitivity following catecholamine synthesis inhibition in man.", "content": "This paper reports a marked decrease in total hours of sleep in depressed and manic patients on days 3 and 4 following discontinuation of alpha-methyl-para-tyrosine (AMPT), a specific inhibitor of the synthesis of the neurotransmitters, norepinephrine and dopamine. Discontinuation of two precursors of biogenic amines, L-dopa and L-tryptophan, produced no changes in total sleep. It is suggested that the decrease in sleep following AMPT may result from catecholamine neuronal receptor hypersensitivity induced during AMPT treatment. Animal data consistent with this hypothesis are reviewed. The importance of studying rebound phenomena following psychoactive drugs and the practical therapeutic implications of these findings are discussed.", "contents": "Sleep and behavioral changes possibly reflecting central receptor hypersensitivity following catecholamine synthesis inhibition in man. This paper reports a marked decrease in total hours of sleep in depressed and manic patients on days 3 and 4 following discontinuation of alpha-methyl-para-tyrosine (AMPT), a specific inhibitor of the synthesis of the neurotransmitters, norepinephrine and dopamine. Discontinuation of two precursors of biogenic amines, L-dopa and L-tryptophan, produced no changes in total sleep. It is suggested that the decrease in sleep following AMPT may result from catecholamine neuronal receptor hypersensitivity induced during AMPT treatment. Animal data consistent with this hypothesis are reviewed. The importance of studying rebound phenomena following psychoactive drugs and the practical therapeutic implications of these findings are discussed."}
{"id": "PMID:197796", "title": "Search for virus specific DNA sequences and viral particles in mitochondria of avian leukemic myeloblasts.", "content": "The intracellular localization of the avian myeloblastosis virus (AMV) genome was studied. Nuclear and mitochondrial DNAs from myeloblasts were examined by hybridization with 32P labeled AMV-RNA of high molecular weight for the presence of virus specific DNA sequences. Nuclear DNA (nDNA) from myeloblasts specifically hybridized with viral RNA, whereas purified closed circular mitochondrial DNA (mtDNA) did not hybridize with viral RNA. It was therefore concluded that viral genome was present in nuclear DNA and not in mitochondrial DNA. Likewise, in normal chick cells, nDNA but not mtDNA hybridized with viral RNA.", "contents": "Search for virus specific DNA sequences and viral particles in mitochondria of avian leukemic myeloblasts. The intracellular localization of the avian myeloblastosis virus (AMV) genome was studied. Nuclear and mitochondrial DNAs from myeloblasts were examined by hybridization with 32P labeled AMV-RNA of high molecular weight for the presence of virus specific DNA sequences. Nuclear DNA (nDNA) from myeloblasts specifically hybridized with viral RNA, whereas purified closed circular mitochondrial DNA (mtDNA) did not hybridize with viral RNA. It was therefore concluded that viral genome was present in nuclear DNA and not in mitochondrial DNA. Likewise, in normal chick cells, nDNA but not mtDNA hybridized with viral RNA."}
{"id": "PMID:197797", "title": "Morphological studies of Gross virus-induced lymphoblasts by scanning electron microscopy.", "content": "The surface of Gross virus-induced murine lymphoblasts and C-type virus particles budding from these cells were investigated under the scanning electron microscope (SEM). The cells appeared spindle-shaped or roughly-rounded with extensive surface features consisting of microvilli, blebs and ruffled membranes. C-type virus particles were detected on the cell membrane as small spherical particles, distinguishable from the microvilli. Clustered virions were observed in some cases. However, the distribution of virions appeared to be random. The surface of the virion was smooth and had no globular units at high magnification. These morphological observations were confirmed in ultrathin sections.", "contents": "Morphological studies of Gross virus-induced lymphoblasts by scanning electron microscopy. The surface of Gross virus-induced murine lymphoblasts and C-type virus particles budding from these cells were investigated under the scanning electron microscope (SEM). The cells appeared spindle-shaped or roughly-rounded with extensive surface features consisting of microvilli, blebs and ruffled membranes. C-type virus particles were detected on the cell membrane as small spherical particles, distinguishable from the microvilli. Clustered virions were observed in some cases. However, the distribution of virions appeared to be random. The surface of the virion was smooth and had no globular units at high magnification. These morphological observations were confirmed in ultrathin sections."}
{"id": "PMID:197798", "title": "Urinary cyclic AMP: relation to calcium balance and comparison of assay methods.", "content": "Urinary adenosine 3',5'-monophosphate (cyclic AMP, cAMP) has been determined in 84 males. Two protein-binding assays were used: the method of Gilman and the Amersham assay kit. The results were in close agreement. The excretion of cAMP was nor correlated to urinary calcium or to estimated calcium intake.", "contents": "Urinary cyclic AMP: relation to calcium balance and comparison of assay methods. Urinary adenosine 3',5'-monophosphate (cyclic AMP, cAMP) has been determined in 84 males. Two protein-binding assays were used: the method of Gilman and the Amersham assay kit. The results were in close agreement. The excretion of cAMP was nor correlated to urinary calcium or to estimated calcium intake."}
{"id": "PMID:197799", "title": "The effect of glucagon on plasma cyclic AMP and glucose concentrations in patients with alcoholic cirrhosis.", "content": "Glucagon was infused intravenously into four patients with alcoholic cirrhosis and five healthy subjects and serial measurements were made of plasma cyclic AMP and glucose concentrations. The results in the cirrhotic patients did not differ significantly from those in healthy subjects.", "contents": "The effect of glucagon on plasma cyclic AMP and glucose concentrations in patients with alcoholic cirrhosis. Glucagon was infused intravenously into four patients with alcoholic cirrhosis and five healthy subjects and serial measurements were made of plasma cyclic AMP and glucose concentrations. The results in the cirrhotic patients did not differ significantly from those in healthy subjects."}
{"id": "PMID:197800", "title": "Effects of dexamethasone, desoxycorticosterone, and ACTH on serum concentrations of thyroxine, 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine.", "content": "The effects of a pure glucocorticoid, dexamethasone, and a pure mineralocorticoid, desoxycorticosterone, on the serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5'-triiodothyronine (reverse T3, rT3) were compared both in healthy subjects and in athyreotic T4-substituted patients. In addition, the effect of exogenous ACTH was examined in healthy subjects. Both in healthy subjects and in T4-substituted athyreotic patients, administration of a single oral dose of dexamethasone caused a rapid and sharp decrease in the serum concentration of T3, and a corresponding increase in the serum concentration of rT3. The T4 concentration was not changed. A single oral dose of desoxycorticosterone evoked no significant changes in the serum concentrations of T3, rT3, or T4 either in healthy subjects or in T4-substituted athyreotic patients. Like dexamethasone, ACTH (two i.v. injections of 60 IU each, at a 6-hour interval) evoked a serum T3 reduction and a serum rT3 increase. Hence, it appears that both endogenous and exogenous glucocorticoids, but not mineralocorticoids, may partially divert the deiodination of T4 from the activating (T4 lead to T3) to the inactivating (T4 leads to rT3) pathway.", "contents": "Effects of dexamethasone, desoxycorticosterone, and ACTH on serum concentrations of thyroxine, 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine. The effects of a pure glucocorticoid, dexamethasone, and a pure mineralocorticoid, desoxycorticosterone, on the serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5'-triiodothyronine (reverse T3, rT3) were compared both in healthy subjects and in athyreotic T4-substituted patients. In addition, the effect of exogenous ACTH was examined in healthy subjects. Both in healthy subjects and in T4-substituted athyreotic patients, administration of a single oral dose of dexamethasone caused a rapid and sharp decrease in the serum concentration of T3, and a corresponding increase in the serum concentration of rT3. The T4 concentration was not changed. A single oral dose of desoxycorticosterone evoked no significant changes in the serum concentrations of T3, rT3, or T4 either in healthy subjects or in T4-substituted athyreotic patients. Like dexamethasone, ACTH (two i.v. injections of 60 IU each, at a 6-hour interval) evoked a serum T3 reduction and a serum rT3 increase. Hence, it appears that both endogenous and exogenous glucocorticoids, but not mineralocorticoids, may partially divert the deiodination of T4 from the activating (T4 lead to T3) to the inactivating (T4 leads to rT3) pathway."}
{"id": "PMID:197801", "title": "The empty sella syndrome analysis of 10 cases.", "content": "Ten cases of the empty sella syndrome are presented. In four a pituitary adenoma had been treated by surgery with or without radiotherapy. In three women there was a close relation pregnancy, and two boys had congenital malformations. Five cases presented with appearances of pseudotomour, and the remainder had cerebrospinal fluid (CSF) fistula. Four fistulas were spontaneous, one was post-traumatic aggravated by the intrasellar implantation of YT-90. Two were occult CSF fistulas causing recurrent meningitis. Gamma cisternography and iodocisternography proved to be good diagnostic tests, both for the empty sella and for CSF fistulas. Nine cases were operated on. In four na intrasellar cyst was present. In the other five an empty sella with deficient or absent diaphragm was found. Treatment of most cases consisted of covering the floor of the sella with lyophilized dura, which was fixed in place with biological glue.", "contents": "The empty sella syndrome analysis of 10 cases. Ten cases of the empty sella syndrome are presented. In four a pituitary adenoma had been treated by surgery with or without radiotherapy. In three women there was a close relation pregnancy, and two boys had congenital malformations. Five cases presented with appearances of pseudotomour, and the remainder had cerebrospinal fluid (CSF) fistula. Four fistulas were spontaneous, one was post-traumatic aggravated by the intrasellar implantation of YT-90. Two were occult CSF fistulas causing recurrent meningitis. Gamma cisternography and iodocisternography proved to be good diagnostic tests, both for the empty sella and for CSF fistulas. Nine cases were operated on. In four na intrasellar cyst was present. In the other five an empty sella with deficient or absent diaphragm was found. Treatment of most cases consisted of covering the floor of the sella with lyophilized dura, which was fixed in place with biological glue."}
{"id": "PMID:197821", "title": "Effect of vitamin D3 and 1,25-dihydroxyvitamin D3 on intestinal transport of phosphate.", "content": "Dietary variations (low calcium, low calcium, low phosphorus, or high strontium) change phosphate transport by the jejunum according to their respective ability to increase or block the synthesis of 1,25-dihydroxyvitamin D3, suggesting that the action of this active sterol underlies the response of intestinal phosphate absorption to vitamin D. 1,25-(OH)2D3 stimulates the active entry of Pi at the mucosal border by its action on protein synthesis. It is attractive to speculate that 1,25-(OH)2D3 might induce the synthesis of a \"phosphate carrier\" protein in the plasma membrane. The interpretation that the enhancement of the maximal velocity of the \"phosphate pump\" by vitamin D is due to the creation of new pump sites would be consistent with this hypothesis.", "contents": "Effect of vitamin D3 and 1,25-dihydroxyvitamin D3 on intestinal transport of phosphate. Dietary variations (low calcium, low calcium, low phosphorus, or high strontium) change phosphate transport by the jejunum according to their respective ability to increase or block the synthesis of 1,25-dihydroxyvitamin D3, suggesting that the action of this active sterol underlies the response of intestinal phosphate absorption to vitamin D. 1,25-(OH)2D3 stimulates the active entry of Pi at the mucosal border by its action on protein synthesis. It is attractive to speculate that 1,25-(OH)2D3 might induce the synthesis of a \"phosphate carrier\" protein in the plasma membrane. The interpretation that the enhancement of the maximal velocity of the \"phosphate pump\" by vitamin D is due to the creation of new pump sites would be consistent with this hypothesis."}
{"id": "PMID:197827", "title": "Effects of neomycin on polyphosphoinositides in inner ear tissues and monomolecular films.", "content": "The effect of neomycin on polyphosphoinositides was studied in vivo and in vitro. In vivo, the incorporation of 32Pi into phosphatidylinositol phosphate and phosphatidylinositol diphosphate was measured in inner ear tissues. Concentrations of neomycin which decreased the electrophysiological response of the chochlea to sound stimulation also decreased labeling of phosphatidylinositol diphosphate. In vitro experiments with brain tissues and polyphosphoinositide extracts indicated a direct interaction between the lipids and neomycin. Neomycin interacts strongly with monomolecular films of polyphosphoinositides. The interaction appears to be complex and is a function of neomycin concentration in the subphase and surface pressure of the film. Condensation of the polyphosphoinositide film is favored at low neomycin concentrations and low film pressures while expansion of the film is favored at high neomycin concentrations and high film pressures. The interactions of neomycin with other negatively charged films (phosphatidyl inositol and phosphatidyl serine) are much weaker, particularly at low neomycin concentrations. The metabolic and physiological consequences of the neomycin/polyphosphoinositide interaction are discussed in regard to the ototoxicity of the drug.", "contents": "Effects of neomycin on polyphosphoinositides in inner ear tissues and monomolecular films. The effect of neomycin on polyphosphoinositides was studied in vivo and in vitro. In vivo, the incorporation of 32Pi into phosphatidylinositol phosphate and phosphatidylinositol diphosphate was measured in inner ear tissues. Concentrations of neomycin which decreased the electrophysiological response of the chochlea to sound stimulation also decreased labeling of phosphatidylinositol diphosphate. In vitro experiments with brain tissues and polyphosphoinositide extracts indicated a direct interaction between the lipids and neomycin. Neomycin interacts strongly with monomolecular films of polyphosphoinositides. The interaction appears to be complex and is a function of neomycin concentration in the subphase and surface pressure of the film. Condensation of the polyphosphoinositide film is favored at low neomycin concentrations and low film pressures while expansion of the film is favored at high neomycin concentrations and high film pressures. The interactions of neomycin with other negatively charged films (phosphatidyl inositol and phosphatidyl serine) are much weaker, particularly at low neomycin concentrations. The metabolic and physiological consequences of the neomycin/polyphosphoinositide interaction are discussed in regard to the ototoxicity of the drug."}
{"id": "PMID:197829", "title": "Cell membranes in cytotoxicity.", "content": "Silica particles are cytotoxic for macrophages because they damage the membranes around secondary lysosomes in which the particles are engulfed. Hydroxyl groups of silicic acid on the surface of the particles form hydrogen bonds with phosphate ester groups of phospholipids and disrupt a variety of natural and artificial membranes. Asbestos fibers induce secretion of hydrolytic enzymes from cultured macrophages. Magnesium hydroxide groups of chrysotile asbestos interact ionically with ionized sialic acid residues of membrane glycoproteins, increase passive cation flux and produce osmotic lysis. The terminal components of complement (C5b-C9) when inserted into the bilayer structure also increase passive cation flux and produce osmotic lysis. The small complement cleavage product C3a is lytic for several cell types, especially malignant cells. The mechanism by which specifically sensitized thymus-derived (T)-lymphocytes kill tumour cells is discussed. Plasma membranes from effector lymphocytes possess considerable cytolytic potential, which is dependent on the activity of a membrane-associated proteinase.", "contents": "Cell membranes in cytotoxicity. Silica particles are cytotoxic for macrophages because they damage the membranes around secondary lysosomes in which the particles are engulfed. Hydroxyl groups of silicic acid on the surface of the particles form hydrogen bonds with phosphate ester groups of phospholipids and disrupt a variety of natural and artificial membranes. Asbestos fibers induce secretion of hydrolytic enzymes from cultured macrophages. Magnesium hydroxide groups of chrysotile asbestos interact ionically with ionized sialic acid residues of membrane glycoproteins, increase passive cation flux and produce osmotic lysis. The terminal components of complement (C5b-C9) when inserted into the bilayer structure also increase passive cation flux and produce osmotic lysis. The small complement cleavage product C3a is lytic for several cell types, especially malignant cells. The mechanism by which specifically sensitized thymus-derived (T)-lymphocytes kill tumour cells is discussed. Plasma membranes from effector lymphocytes possess considerable cytolytic potential, which is dependent on the activity of a membrane-associated proteinase."}
{"id": "PMID:197830", "title": "Lead actions on sodium-plus-potassium-activated adenosinetriphosphatase from electroplax, rat brain, and rat kidney.", "content": "Inorganic lead ion, in micromolar concentrations, reversibly inhibits the sodium-plus-potassium-activated adenosinetriphosphatase (ATPase) and potassium-activated p-nitrophenylphosphatase (NPPase) activities of microsomal fractions from electric organ, rat kidney, and rat brain. In the presence of 3 mM MgC12 and 3 mM ATP, the concentrations of PbC12 producing half-maximal inhibition of the ATPase from these tissues are 4 X 10(-6) M, 20 X 10(-6) M, and 55 X 10(-6) M, respectively. The corresponding values for inhibition of the NPPase are 10(-6) M, 53 X  10(-6) M, and 22 X 10(-6) M. PbC12 also stimulates the phosphorylation by [gamma-32P]ATP of a microsomal protein from all three tissues in the absence of added sodium ion. This reaction was extensively studied with electroplax microsomes. In common with the well-known Na+-dependent phosphorylation of (Na+ + K+)-ATPase, the Pb2 -dependent reaction is inhibited by ouabain, specific for ATP, dependent on Mg2+, and yields and acid-stable phosphoprotein with a molecular weight of 98,000 in sodium dodecylsulfate. The Pb2+-dependent phosphoprotein, however, is not sensitive to K+. These observations are pertinent to the biochemistry and toxicity of inorganic lead in tissues and to the molecular mechanism of the cation transport enzyme.", "contents": "Lead actions on sodium-plus-potassium-activated adenosinetriphosphatase from electroplax, rat brain, and rat kidney. Inorganic lead ion, in micromolar concentrations, reversibly inhibits the sodium-plus-potassium-activated adenosinetriphosphatase (ATPase) and potassium-activated p-nitrophenylphosphatase (NPPase) activities of microsomal fractions from electric organ, rat kidney, and rat brain. In the presence of 3 mM MgC12 and 3 mM ATP, the concentrations of PbC12 producing half-maximal inhibition of the ATPase from these tissues are 4 X 10(-6) M, 20 X 10(-6) M, and 55 X 10(-6) M, respectively. The corresponding values for inhibition of the NPPase are 10(-6) M, 53 X  10(-6) M, and 22 X 10(-6) M. PbC12 also stimulates the phosphorylation by [gamma-32P]ATP of a microsomal protein from all three tissues in the absence of added sodium ion. This reaction was extensively studied with electroplax microsomes. In common with the well-known Na+-dependent phosphorylation of (Na+ + K+)-ATPase, the Pb2 -dependent reaction is inhibited by ouabain, specific for ATP, dependent on Mg2+, and yields and acid-stable phosphoprotein with a molecular weight of 98,000 in sodium dodecylsulfate. The Pb2+-dependent phosphoprotein, however, is not sensitive to K+. These observations are pertinent to the biochemistry and toxicity of inorganic lead in tissues and to the molecular mechanism of the cation transport enzyme."}
{"id": "PMID:197838", "title": "Investigations into the cardiac effects of tolazoline in guinea pig atria and ventricular strips.", "content": "The positive inotropic, chronotropic and cyclic AMP producing effects of tolazoline were studied on atrial and ventricular preparations obtained from guinea pig heart. (1) The direct positive inotropic effects of tolazoline on the paced left atrial preparation from the guinea pig hearts was blocked by promethazine, but not by burimamide. Tolazoline did not elevate cyclic AMP levels in this preparation. (2) Tolazoline produced a positive chronotropic effect which was blocked by burimamide and not by promethazine and caused a 2-3 fold elevation of cyclic AMP in spontaneously beating right atria. (3) Burimamide antagonized the inotropic and cyclic AMP increasing effects of tolazoline on electrically driven ventricular strips. (4) The effects of tolazoline were unchanged by reserpine pretreatment of the guinea pigs or by prior exposure to phentolamine or propranolol. (5) These results suggest that tolazoline can activate both H1 and H2 receptors in the guinea pig heart. Furthermore the data suggests that H2 receptors are present in right atria and ventricle and that such receptors are associated with cyclic AMP. H1 receptors are present in the left atria and are not associated with the cyclic nucleotide.", "contents": "Investigations into the cardiac effects of tolazoline in guinea pig atria and ventricular strips. The positive inotropic, chronotropic and cyclic AMP producing effects of tolazoline were studied on atrial and ventricular preparations obtained from guinea pig heart. (1) The direct positive inotropic effects of tolazoline on the paced left atrial preparation from the guinea pig hearts was blocked by promethazine, but not by burimamide. Tolazoline did not elevate cyclic AMP levels in this preparation. (2) Tolazoline produced a positive chronotropic effect which was blocked by burimamide and not by promethazine and caused a 2-3 fold elevation of cyclic AMP in spontaneously beating right atria. (3) Burimamide antagonized the inotropic and cyclic AMP increasing effects of tolazoline on electrically driven ventricular strips. (4) The effects of tolazoline were unchanged by reserpine pretreatment of the guinea pigs or by prior exposure to phentolamine or propranolol. (5) These results suggest that tolazoline can activate both H1 and H2 receptors in the guinea pig heart. Furthermore the data suggests that H2 receptors are present in right atria and ventricle and that such receptors are associated with cyclic AMP. H1 receptors are present in the left atria and are not associated with the cyclic nucleotide."}
{"id": "PMID:197839", "title": "Human synovial fibroblasts: the relationships between cyclic AMP, bradykinin, and prostaglandins.", "content": "Human synovial fibroblasts in culture respond to bradykinin (8 X 10(-9) M) with an increment in intracellular cyclic AMP concentration. These bradykinin (BK) concentrations are comparable to levels of the nonapeptide found in pathological synovial effusions. The cyclic AMP response to BK is enhanced by a heat stable factor(s) in fetal calf serum (FCS) and by the addition of arachidonic acid (AA) to monolayer cultures incubated in serum-free media. Synovial fibroblasts initially treated with BK are refractory to rechallenge with this agent as measured by the absence of an increment in cyclic AMP. These BK refractory cells do respond with significant increment in cyclic AMP to challenge with prostaglandin E1 (PGE1). Cells that have become refractory to PGE1 stimulation respond to BK. this suggests that a receptor or activator system different from the one for PGE1 and PGE2 exists for BK. When both BK and PGE1 are incubated together with synovial fibroblasts, the cyclic AMP response elicited is more than additive as compared to the response of each hormone separately. Indomethacin (IM) inhibits the BK evoked cyclic AMP response unless cell cultures are pretreated with PGE1. The PGE1 analog, 7-oxa-13-prostynoic acid, is a better inhibitor of the cyclic AMP response induced by BK than by PGE1. BK does not elicit a cyclic AMP response solely by elaborating PGE1, yet the prostaglandin pathway and its products seem to have a role in the degree of the cyclic AMP response to BK challenge.", "contents": "Human synovial fibroblasts: the relationships between cyclic AMP, bradykinin, and prostaglandins. Human synovial fibroblasts in culture respond to bradykinin (8 X 10(-9) M) with an increment in intracellular cyclic AMP concentration. These bradykinin (BK) concentrations are comparable to levels of the nonapeptide found in pathological synovial effusions. The cyclic AMP response to BK is enhanced by a heat stable factor(s) in fetal calf serum (FCS) and by the addition of arachidonic acid (AA) to monolayer cultures incubated in serum-free media. Synovial fibroblasts initially treated with BK are refractory to rechallenge with this agent as measured by the absence of an increment in cyclic AMP. These BK refractory cells do respond with significant increment in cyclic AMP to challenge with prostaglandin E1 (PGE1). Cells that have become refractory to PGE1 stimulation respond to BK. this suggests that a receptor or activator system different from the one for PGE1 and PGE2 exists for BK. When both BK and PGE1 are incubated together with synovial fibroblasts, the cyclic AMP response elicited is more than additive as compared to the response of each hormone separately. Indomethacin (IM) inhibits the BK evoked cyclic AMP response unless cell cultures are pretreated with PGE1. The PGE1 analog, 7-oxa-13-prostynoic acid, is a better inhibitor of the cyclic AMP response induced by BK than by PGE1. BK does not elicit a cyclic AMP response solely by elaborating PGE1, yet the prostaglandin pathway and its products seem to have a role in the degree of the cyclic AMP response to BK challenge."}
{"id": "PMID:197841", "title": "Multiple symmetrical fractures of bone of unresolved etiology.", "content": "The clinical, laboratory, and radiologic picture of a unique patient with symmetrical fractures of the anterior tibial midshafts, dorsal ulnar cortices, and lateral metatarsals is presented. The findings are not compatible with a diagnosis of osteogenesis imperfecta or osteomalacia despite osseous fragility. The elevated serum pyrophosphate and low urine phosphate content suggest that abnormalities in phosphate metabolism may have contributed to the formation of bone which is biochemically and structurally deficient.", "contents": "Multiple symmetrical fractures of bone of unresolved etiology. The clinical, laboratory, and radiologic picture of a unique patient with symmetrical fractures of the anterior tibial midshafts, dorsal ulnar cortices, and lateral metatarsals is presented. The findings are not compatible with a diagnosis of osteogenesis imperfecta or osteomalacia despite osseous fragility. The elevated serum pyrophosphate and low urine phosphate content suggest that abnormalities in phosphate metabolism may have contributed to the formation of bone which is biochemically and structurally deficient."}
{"id": "PMID:197842", "title": "\"Hot spot\" on hepatic scintigraphy and radionuclide venacavography.", "content": "Seven patients showing a localized area of increased uptake (hot spot) on 99mTc sulfur colloid liver scans are described. Four also had dynamic studies. In five patients the hot spot was associated with superior vena caval obstruction, in one it was associated with inferior vena caval obstruction, and in one with a hepatoma. Although a hot spot on static liver images usually indicates superior vena caval obstruction, the addition of radionuclide venacavography is recommended to confirm the diagnosis. A hot spot in the liver area in a radionuclide venogram of the lower limbs suggests inferior vena caval obstruction with collaterals via the liver.", "contents": "\"Hot spot\" on hepatic scintigraphy and radionuclide venacavography. Seven patients showing a localized area of increased uptake (hot spot) on 99mTc sulfur colloid liver scans are described. Four also had dynamic studies. In five patients the hot spot was associated with superior vena caval obstruction, in one it was associated with inferior vena caval obstruction, and in one with a hepatoma. Although a hot spot on static liver images usually indicates superior vena caval obstruction, the addition of radionuclide venacavography is recommended to confirm the diagnosis. A hot spot in the liver area in a radionuclide venogram of the lower limbs suggests inferior vena caval obstruction with collaterals via the liver."}
{"id": "PMID:197843", "title": "Angiographic observations on chemodectomas of the head and neck.", "content": "Angiographic experience with chemodectomas in 21 patients is reviewed. Arterial supply was identified from the vertebral artery, the internal carotid artery, and branches of the external carotid artery. A striated cephalad extension from a cervical chemodectoma (five patients) is believed to represent arterial supply to tumor in vein. In two patients, internal and external carotid arteriograms did not opacify important arteries originating near the carotid bifurcation. Retrograde filling of sigmoid sinus (four patients), tumor mass in jugular vein (two patients), and arteriovenous shunting (nine patients) were observed during the venous phase. Thorough angiogra phy is essential for evaluation of chemodectomas of the head and neck.", "contents": "Angiographic observations on chemodectomas of the head and neck. Angiographic experience with chemodectomas in 21 patients is reviewed. Arterial supply was identified from the vertebral artery, the internal carotid artery, and branches of the external carotid artery. A striated cephalad extension from a cervical chemodectoma (five patients) is believed to represent arterial supply to tumor in vein. In two patients, internal and external carotid arteriograms did not opacify important arteries originating near the carotid bifurcation. Retrograde filling of sigmoid sinus (four patients), tumor mass in jugular vein (two patients), and arteriovenous shunting (nine patients) were observed during the venous phase. Thorough angiogra phy is essential for evaluation of chemodectomas of the head and neck."}
{"id": "PMID:197844", "title": "Hand radiographic measurements in growth hormone deficiency before and after treatment.", "content": "Hand radiographs in 10 male patients (eight white, two black) with isolated growth hormone deficiency were studied before and after treatment. The length of the second metacarpal was the most significantly depressed measurement when considered by chronologic age and responded most to treatment with human growth hormone. All patients had osteoporosis even when evaluated by height age. The bone mass improved with treatment by subperiosteal new bone apposition. Skeletal maturation was retarded with the carpals showing more severe retardation than the tubular bones and responding more dramatically to treatment. The depression in height age and carpal age was very similar, indicating that the carpal age may have the greatest correlation with height. The greater sensitivity of the carpal age deficiency of growth hormone and its greater response to treatment suggest that the carpal age and the phalangeal-metacarpal age should be considered independently during evaluation of skeletal maturation.", "contents": "Hand radiographic measurements in growth hormone deficiency before and after treatment. Hand radiographs in 10 male patients (eight white, two black) with isolated growth hormone deficiency were studied before and after treatment. The length of the second metacarpal was the most significantly depressed measurement when considered by chronologic age and responded most to treatment with human growth hormone. All patients had osteoporosis even when evaluated by height age. The bone mass improved with treatment by subperiosteal new bone apposition. Skeletal maturation was retarded with the carpals showing more severe retardation than the tubular bones and responding more dramatically to treatment. The depression in height age and carpal age was very similar, indicating that the carpal age may have the greatest correlation with height. The greater sensitivity of the carpal age deficiency of growth hormone and its greater response to treatment suggest that the carpal age and the phalangeal-metacarpal age should be considered independently during evaluation of skeletal maturation."}
{"id": "PMID:197845", "title": "Toxicological evaluations of some brominated biphenyls.", "content": "Extensive toxicological studies were carried out to define the probable hazard of octabromobiphenyl (OBB) to workers, users, and the environment. OBB had low acute toxicity in mammals and birds by various routes of administration. It was essentially non-irritating to rabbit eyes, non-irritating to human skin and caused only mild skin irritation and no sensitization in the guinea pig. OBB caused equivocal effects in the rat fetus. OBB was stored in the body fat of rats and caused liver enlargement at high single doses or low repeated doses. The studies indicate probable low safety factors in application and use and probable bioaccumulation. Hexabromobiphenyl (HBB) was more acutely toxic than OBB by skin absorption in the rabbit and caused liver enlargement at lower single doses.", "contents": "Toxicological evaluations of some brominated biphenyls. Extensive toxicological studies were carried out to define the probable hazard of octabromobiphenyl (OBB) to workers, users, and the environment. OBB had low acute toxicity in mammals and birds by various routes of administration. It was essentially non-irritating to rabbit eyes, non-irritating to human skin and caused only mild skin irritation and no sensitization in the guinea pig. OBB caused equivocal effects in the rat fetus. OBB was stored in the body fat of rats and caused liver enlargement at high single doses or low repeated doses. The studies indicate probable low safety factors in application and use and probable bioaccumulation. Hexabromobiphenyl (HBB) was more acutely toxic than OBB by skin absorption in the rabbit and caused liver enlargement at lower single doses."}
{"id": "PMID:197846", "title": "Application of counterimmunoelectrophoresis in rapid detection of cytomegalovirus antibodies.", "content": "Determination of cytomegalovirus antibodies by counterimmune-electrophoresis correlated well with results of complement-fixation antibody studies. The sensitivity and specificity of the counterimmunoelectrophoresis method (vs. complement fixation) was 88.9%. Fourfold antibody increases detected by complement fixation were also detected by counterimmunoelectrophoresis. In addition, no cross-reaction was observed in the counterimmunoelectrophoresis assay between other DNA viral antisera and cytomegalovirus antigen (Ad-169).", "contents": "Application of counterimmunoelectrophoresis in rapid detection of cytomegalovirus antibodies. Determination of cytomegalovirus antibodies by counterimmune-electrophoresis correlated well with results of complement-fixation antibody studies. The sensitivity and specificity of the counterimmunoelectrophoresis method (vs. complement fixation) was 88.9%. Fourfold antibody increases detected by complement fixation were also detected by counterimmunoelectrophoresis. In addition, no cross-reaction was observed in the counterimmunoelectrophoresis assay between other DNA viral antisera and cytomegalovirus antigen (Ad-169)."}
{"id": "PMID:197847", "title": "Multiple apocrine fibroadenomas of the anal skin.", "content": "The authors describe an apocrine sweat gland tumor that resembles intracanalicular fibroadenoma of the breast. Three of these tumors were present in the anal skin of their patient.", "contents": "Multiple apocrine fibroadenomas of the anal skin. The authors describe an apocrine sweat gland tumor that resembles intracanalicular fibroadenoma of the breast. Three of these tumors were present in the anal skin of their patient."}
{"id": "PMID:197848", "title": "Atypical fibrous histiocytoma of the humerus: a light and electron microscopic study.", "content": "A unique osseous tumor, which arose in the humerus of a 44-year-old white man, is reported. The lesion was designated atypical fibrous histiocytoma because of the absence of atypical mitoses despite prominent nuclear pleomorphism of tumor cells. The tumor was composed mainly of spindle cells, tightly packed in a storiform pattern. Clear histiocytes and tumor giant cells were occasionally seen. Toward the proximal and distal ends, the tumor showed increasing fibrogenesis, and the ends were composed of areas of packed clear histiocytes and acellular myxoid matrix with focal calcification. Ultrastructurally, five cell types comprised the tumor, but fibroblast-like cells predominated. Histiocyte-like, xanthomatous, giant and undifferentiated cells were observed only occasionally. The patient has been followed for five years after disarticulation without developing evidence of distant metastasis.", "contents": "Atypical fibrous histiocytoma of the humerus: a light and electron microscopic study. A unique osseous tumor, which arose in the humerus of a 44-year-old white man, is reported. The lesion was designated atypical fibrous histiocytoma because of the absence of atypical mitoses despite prominent nuclear pleomorphism of tumor cells. The tumor was composed mainly of spindle cells, tightly packed in a storiform pattern. Clear histiocytes and tumor giant cells were occasionally seen. Toward the proximal and distal ends, the tumor showed increasing fibrogenesis, and the ends were composed of areas of packed clear histiocytes and acellular myxoid matrix with focal calcification. Ultrastructurally, five cell types comprised the tumor, but fibroblast-like cells predominated. Histiocyte-like, xanthomatous, giant and undifferentiated cells were observed only occasionally. The patient has been followed for five years after disarticulation without developing evidence of distant metastasis."}
{"id": "PMID:197849", "title": "Hepatoma presenting as lower gastrointestinal bleeding.", "content": "A 61-year old white male, known to have alcoholic cirrhosis, presented with massive fresh bleeding per rectum. Various investigations failed to ascertain the cause of bleeding. Hepatoma of the liver was revealed by selective hepatic and superior mesenteric angiography. Massive lower gastrointestinal bleeding occurred again one month later and was rapidly followed by death from hepatic coma. An extensive hepatoma infiltrating the adjacent hepatic flexure of the colon was found at autopsy, the colonic infiltration explaining the lower gastrointestinal hemorrhage.", "contents": "Hepatoma presenting as lower gastrointestinal bleeding. A 61-year old white male, known to have alcoholic cirrhosis, presented with massive fresh bleeding per rectum. Various investigations failed to ascertain the cause of bleeding. Hepatoma of the liver was revealed by selective hepatic and superior mesenteric angiography. Massive lower gastrointestinal bleeding occurred again one month later and was rapidly followed by death from hepatic coma. An extensive hepatoma infiltrating the adjacent hepatic flexure of the colon was found at autopsy, the colonic infiltration explaining the lower gastrointestinal hemorrhage."}
{"id": "PMID:197850", "title": "Effects of progesterone on some enzymes of fat and carbohydrate metabolism in rat liver.", "content": "The known effect of progesterone on carbohydrate metabolism prompted a study of some of the hepatic \"lipogenic\" and \"gluconeogenic\" enzymes in rats treated with progesterone. Several enzymes providing lipid precursors (phosphofructokinase, malic enzyme, glucose-6-phosphate dehydrogenase, and citrate cleavage enzyme) showed increased specific activity. These changes may represent insulin effects. Specific activity of phosphoenolpyruvate carboxykinase, usually associated with control of gluconeogenesis, was also increased. The latter is compatible with increased capability for glycogenesis, which is recognized as a progesterone effect.", "contents": "Effects of progesterone on some enzymes of fat and carbohydrate metabolism in rat liver. The known effect of progesterone on carbohydrate metabolism prompted a study of some of the hepatic \"lipogenic\" and \"gluconeogenic\" enzymes in rats treated with progesterone. Several enzymes providing lipid precursors (phosphofructokinase, malic enzyme, glucose-6-phosphate dehydrogenase, and citrate cleavage enzyme) showed increased specific activity. These changes may represent insulin effects. Specific activity of phosphoenolpyruvate carboxykinase, usually associated with control of gluconeogenesis, was also increased. The latter is compatible with increased capability for glycogenesis, which is recognized as a progesterone effect."}
{"id": "PMID:197852", "title": "Ocular findings associated with encephalomyelitis caused by Herpesvirus simiae.", "content": "A 29-year-old monkey handler developed acute encephalomyelitis with serological evidence of Herpesvirus simiae infection. He had sudden unilateral loss of vision on the 32nd day of illness caused by vitreous hemorrhage. This cleared gradually, revealing chorioretinal scarring and a gliovascular vitreous band which eventually caused local tractional retinal detachment.", "contents": "Ocular findings associated with encephalomyelitis caused by Herpesvirus simiae. A 29-year-old monkey handler developed acute encephalomyelitis with serological evidence of Herpesvirus simiae infection. He had sudden unilateral loss of vision on the 32nd day of illness caused by vitreous hemorrhage. This cleared gradually, revealing chorioretinal scarring and a gliovascular vitreous band which eventually caused local tractional retinal detachment."}
{"id": "PMID:197854", "title": "Pseudotumoral aspect of posttraumatic digital synovitis.", "content": "A case of posttraumatic subacute synovitis with pseudotumor of the digit with bone lesions on plain film is reported. Arteriography showed a pattern of hypervascularity  that did not appear malignant and evoked a benign tumor of the synovial. Biopsy helped establish diagnosis of common subacute synovitis. Swelling disappeared spontaneously during subsequent months. Diagnosis of villonodular synovitis is difficllt when proliferation of histiocytes is present.", "contents": "Pseudotumoral aspect of posttraumatic digital synovitis. A case of posttraumatic subacute synovitis with pseudotumor of the digit with bone lesions on plain film is reported. Arteriography showed a pattern of hypervascularity  that did not appear malignant and evoked a benign tumor of the synovial. Biopsy helped establish diagnosis of common subacute synovitis. Swelling disappeared spontaneously during subsequent months. Diagnosis of villonodular synovitis is difficllt when proliferation of histiocytes is present."}
{"id": "PMID:197859", "title": "In vitro activation of adenylate cyclase by parathyroid hormone and calcitonin during normal and hydrocortisone-induced cleft palate development in the golden hamster.", "content": "An adenylate cyclase highly responsive to stimulation by parathyroid hormone (PTH) and calcitonin (CT) in vitro was observed at certain times during normal prenatal development of the maxillary-palatal process complex in the golden hamster. Responses of the enzyme to these hormones were barely detectible at the earliest stage examined (day 10/20). The enzyme became extremely sensitive to activation by either hormone during the time of rapid growth of the palatal processes (day 11/20) and during fusion between the palatal processes (day 12/20). Thereafter, responses were greatly diminished and little or no activation of adenylate cyclase was observed until birth. Adenylate cyclase from fetuses in which clefts of the secondary palate were induced by maternal treatment with hydrocortisone (50 mg) on day 11/3 also displayed an enhanced sensitivity to PTH and CT  on day 11/20, but the sensitivity of the enzyme was greatly decreased from that in normal animals during the normal time of palatal fusion (day 12/20) and was barely detectible or absent at the remaining time periods studied (days 13/20 and 14/20). Addition of hydrocortisone to the incubation mixture, either separately or in combination with PTH or CT, did not remarkably affect the response of adenylate cyclase to these hormones. Moreover, the appearance of the adenylate cyclase sensitive to hormonal activation did not result from changes in phosphodiesterase activity during palatal maturation.", "contents": "In vitro activation of adenylate cyclase by parathyroid hormone and calcitonin during normal and hydrocortisone-induced cleft palate development in the golden hamster. An adenylate cyclase highly responsive to stimulation by parathyroid hormone (PTH) and calcitonin (CT) in vitro was observed at certain times during normal prenatal development of the maxillary-palatal process complex in the golden hamster. Responses of the enzyme to these hormones were barely detectible at the earliest stage examined (day 10/20). The enzyme became extremely sensitive to activation by either hormone during the time of rapid growth of the palatal processes (day 11/20) and during fusion between the palatal processes (day 12/20). Thereafter, responses were greatly diminished and little or no activation of adenylate cyclase was observed until birth. Adenylate cyclase from fetuses in which clefts of the secondary palate were induced by maternal treatment with hydrocortisone (50 mg) on day 11/3 also displayed an enhanced sensitivity to PTH and CT  on day 11/20, but the sensitivity of the enzyme was greatly decreased from that in normal animals during the normal time of palatal fusion (day 12/20) and was barely detectible or absent at the remaining time periods studied (days 13/20 and 14/20). Addition of hydrocortisone to the incubation mixture, either separately or in combination with PTH or CT, did not remarkably affect the response of adenylate cyclase to these hormones. Moreover, the appearance of the adenylate cyclase sensitive to hormonal activation did not result from changes in phosphodiesterase activity during palatal maturation."}
{"id": "PMID:197860", "title": "Dishabituation of mesencephalic reticular neurons by anesthetics.", "content": "To determine whether neuronal firing is affected by anesthetics, the behavior of neurons in the mesencephalic reticular formation in response to repetitive somatosensory stimulation at 2/sec was studied during wakefulness and during nitrous oxide, halothane, and thiopental anesthesia in the cat. With clinical doses of the three anesthetics there were simultaneous blockades of both initial facilitation (28 of 32) and subsequent habituation (31 of 32) of the evoked responses in a majority of the mesencephalic reticular formation neurons. This dishabituation phenomenon was most prominent with thiopental and least prominent with nitrous oxide. Thus, it is suggested that progressive inactivation of not only the facilitatory process but also the inhibitory process in the neuronal activities of the mesencephalic reticular formation is associated with the so-called \"anesthetic state\" produced by these three anesthetics.", "contents": "Dishabituation of mesencephalic reticular neurons by anesthetics. To determine whether neuronal firing is affected by anesthetics, the behavior of neurons in the mesencephalic reticular formation in response to repetitive somatosensory stimulation at 2/sec was studied during wakefulness and during nitrous oxide, halothane, and thiopental anesthesia in the cat. With clinical doses of the three anesthetics there were simultaneous blockades of both initial facilitation (28 of 32) and subsequent habituation (31 of 32) of the evoked responses in a majority of the mesencephalic reticular formation neurons. This dishabituation phenomenon was most prominent with thiopental and least prominent with nitrous oxide. Thus, it is suggested that progressive inactivation of not only the facilitatory process but also the inhibitory process in the neuronal activities of the mesencephalic reticular formation is associated with the so-called \"anesthetic state\" produced by these three anesthetics."}
{"id": "PMID:197862", "title": "[Enzymatic determination of blood ethanol with centrifugal analyser].", "content": "An automated method for ethanol determination on Gemsaec centrifugal fast analyser is described. The measurements have been done by a non linear two-point kinetic method during 10 minutes. The suitability of the proposed method has been evaluated by determination of the detection limit and the recovery. The method is applicated to whole blood and to plasma with and without initial perchloric acid deproteinization. Similar results are obtained for the different samples.", "contents": "[Enzymatic determination of blood ethanol with centrifugal analyser]. An automated method for ethanol determination on Gemsaec centrifugal fast analyser is described. The measurements have been done by a non linear two-point kinetic method during 10 minutes. The suitability of the proposed method has been evaluated by determination of the detection limit and the recovery. The method is applicated to whole blood and to plasma with and without initial perchloric acid deproteinization. Similar results are obtained for the different samples."}
{"id": "PMID:197863", "title": "Neurologic manifestations in sarcoidosis: review of the literature, with a report of 23 cases.", "content": "Nervous system involvement by sarcoidosis has been considered rare, yet more than 400 cases have been reported. We present 23 additional cases here, including 14 with autopsies, and we review the literature. The overall frequency of neurologic involvement is 5%. Patients usually have other stigmata of sarcoidosis; however, neurologic dysfunction is frequently the presenting finding. The protean manifestations of central nervous system (CNS) involvement usually occur in the early phase of the disease, while those of peripheral nervous system and skeletal muscle involvement are characteristically seen in the chronic stages. Basal granulomatous meningitis causes most of the CNS manifestations either by infiltration or compression of adjacent structures. Steroids are the mainstay of therapy, and the overall response is quite variable. The course is also variable, being transient in some and chronic in others. The prognosis is better with peripheral than with central nervous system involvement.", "contents": "Neurologic manifestations in sarcoidosis: review of the literature, with a report of 23 cases. Nervous system involvement by sarcoidosis has been considered rare, yet more than 400 cases have been reported. We present 23 additional cases here, including 14 with autopsies, and we review the literature. The overall frequency of neurologic involvement is 5%. Patients usually have other stigmata of sarcoidosis; however, neurologic dysfunction is frequently the presenting finding. The protean manifestations of central nervous system (CNS) involvement usually occur in the early phase of the disease, while those of peripheral nervous system and skeletal muscle involvement are characteristically seen in the chronic stages. Basal granulomatous meningitis causes most of the CNS manifestations either by infiltration or compression of adjacent structures. Steroids are the mainstay of therapy, and the overall response is quite variable. The course is also variable, being transient in some and chronic in others. The prognosis is better with peripheral than with central nervous system involvement."}
{"id": "PMID:197867", "title": "The effect of a topical anesthetic on the recovery of Herpes simplex virus.", "content": "The effect of proparacaine hydrochloride (Ophthaine), a commonly used topical ocular anesthetic, on the recovery of types 1 and 2 herpes simplex virus (HSV) was studied in vitro and in vivo. In the in vitro studies, the titers of both virus types were significantly lower after exposing them to Ophthaine than after exposing them to a control solution. but in the recovery of virus from corneal scrapings from HSV-infected rabbit eyes, collected on the third and seventh days of clinical disease, there was no significant difference between the Ophthaine-treated eyes and the controls. We explored the possible reasons for the disparity between these in vitro and in vivo results.", "contents": "The effect of a topical anesthetic on the recovery of Herpes simplex virus. The effect of proparacaine hydrochloride (Ophthaine), a commonly used topical ocular anesthetic, on the recovery of types 1 and 2 herpes simplex virus (HSV) was studied in vitro and in vivo. In the in vitro studies, the titers of both virus types were significantly lower after exposing them to Ophthaine than after exposing them to a control solution. but in the recovery of virus from corneal scrapings from HSV-infected rabbit eyes, collected on the third and seventh days of clinical disease, there was no significant difference between the Ophthaine-treated eyes and the controls. We explored the possible reasons for the disparity between these in vitro and in vivo results."}
{"id": "PMID:197864", "title": "[Detection of small amounts of viruses (enteroviruses) in drinking water (author's transl)].", "content": "A simple detection method of enteroviruses and adenoviruses in drinking water has been performed, using adsorption-elution on to cellulose nitrate membranes. Average of enteroviruses recovering is varying from 23 to 80% when 30 liters of water containing 60 PFU are monitored. Only 10% of adenoviruses are recovered in the same conditions. This method allowed us to detect 12 PFU of enteroviruses in 120 liters of water. Recovering of 1 PFU in 10 liters when examining more than 100 liters is reproducible.", "contents": "[Detection of small amounts of viruses (enteroviruses) in drinking water (author's transl)]. A simple detection method of enteroviruses and adenoviruses in drinking water has been performed, using adsorption-elution on to cellulose nitrate membranes. Average of enteroviruses recovering is varying from 23 to 80% when 30 liters of water containing 60 PFU are monitored. Only 10% of adenoviruses are recovered in the same conditions. This method allowed us to detect 12 PFU of enteroviruses in 120 liters of water. Recovering of 1 PFU in 10 liters when examining more than 100 liters is reproducible."}
{"id": "PMID:197869", "title": "Prolactin content of the pituitary gland in response to hypertonic saline medium, antithyroid drugs, methallibure and thyroxine in a freshwater teleost Heteropneustes fossilis.", "content": "Variations in the prolactin content of the pituitary gland in response to different treatments were studied in a freshwater catfish, H. fossilis. One week of saline (1% NaCl medium) treatment reduced the pituitary prolactin content but enhanced the serum prolactin level showing release of prolactin from the pituitary gland. Two weeks of saline treatment reduced pituitary as well as serum prolactin content presumably a result of reduced prolactin synthesis in the pituitary gland. This reduction of synthetic activity in this species is probably due to a drop in prolactin requirement. All the antithyroid durgs tested as well as L-thyroxine decreased the pituitary prolactin content. Methallibure administration induced the release of prolactin from the pituitary as evidenced by the lowered prolactin level in this gland and a simultaneous increase in the prolactin content of the serum.", "contents": "Prolactin content of the pituitary gland in response to hypertonic saline medium, antithyroid drugs, methallibure and thyroxine in a freshwater teleost Heteropneustes fossilis. Variations in the prolactin content of the pituitary gland in response to different treatments were studied in a freshwater catfish, H. fossilis. One week of saline (1% NaCl medium) treatment reduced the pituitary prolactin content but enhanced the serum prolactin level showing release of prolactin from the pituitary gland. Two weeks of saline treatment reduced pituitary as well as serum prolactin content presumably a result of reduced prolactin synthesis in the pituitary gland. This reduction of synthetic activity in this species is probably due to a drop in prolactin requirement. All the antithyroid durgs tested as well as L-thyroxine decreased the pituitary prolactin content. Methallibure administration induced the release of prolactin from the pituitary as evidenced by the lowered prolactin level in this gland and a simultaneous increase in the prolactin content of the serum."}
{"id": "PMID:197870", "title": "[Vip in human neonates and infants. As measured by radioimmunoassay and radioreceptorassay (author's transl)].", "content": "The Vasoactive Intestinal Peptide (VIP) was assayed in the gut of human neonates and premature infants immediately after death or surgery. In these conditions, values ranged between 150 and 740 ng/g of bioled tissue. The implication of VIP in Vermer-Morrison syndrome is further assessed by the correlation between clinical symptomatology and plasma VIP levels. The immunoassayable VIP (IA-VIP) extracted from normal gut or tumor is shown to fully interact with specific receptor for VIP in liver. This fact suggests the biological potency of IA-VIP.", "contents": "[Vip in human neonates and infants. As measured by radioimmunoassay and radioreceptorassay (author's transl)]. The Vasoactive Intestinal Peptide (VIP) was assayed in the gut of human neonates and premature infants immediately after death or surgery. In these conditions, values ranged between 150 and 740 ng/g of bioled tissue. The implication of VIP in Vermer-Morrison syndrome is further assessed by the correlation between clinical symptomatology and plasma VIP levels. The immunoassayable VIP (IA-VIP) extracted from normal gut or tumor is shown to fully interact with specific receptor for VIP in liver. This fact suggests the biological potency of IA-VIP."}
{"id": "PMID:197871", "title": "[Islet cell tumor with diarrhea and diabetes (glucagonoma?) associated with hyperparathyroidism. Long-term results of local-regional treatment with streptozotocin].", "content": "A case report of endocrine pancreatic tumour associated with diabetes and hyperparathyroidism is presented. Some arguments are in favour of a glucagonoma. Despite the absence of beta-cells in tumour, an exceptional result was obtained by use of Streptozotocin. This case brings up the relations between endocrine pancreatic tumours and parathyroid, and may be included in polyglandular adenoma syndrome.", "contents": "[Islet cell tumor with diarrhea and diabetes (glucagonoma?) associated with hyperparathyroidism. Long-term results of local-regional treatment with streptozotocin]. A case report of endocrine pancreatic tumour associated with diabetes and hyperparathyroidism is presented. Some arguments are in favour of a glucagonoma. Despite the absence of beta-cells in tumour, an exceptional result was obtained by use of Streptozotocin. This case brings up the relations between endocrine pancreatic tumours and parathyroid, and may be included in polyglandular adenoma syndrome."}
{"id": "PMID:197875", "title": "Subacute sensory neuropathy: a remote effect of carcinoma.", "content": "Seven patients with subacute sensory neuropathy are described and the findings in 29 previously reported patients are reviewed. The presence of this characteristic neurological disorder strongly suggests an accompanying neoplasm. Five of 7 patients had cancer, and 4 died. Autopsy was performed on 3, and pathological analysis revealed inflammation and degeneration of dorsal root ganglia and degeneration of posterior roots and posterior columns of the spinal cord. The dorsal root ganglion was biopsied in 4 patients and showed similar inflammatory lesions. Electron microscopical studies showed inflammation and neuronal degeneration. No viral particles were seen. Viral cultures of the biopsied ganglia from 4 patients were negative. Antineuronal antibodies were not detected in 2 patients. The cause of this syndrome is unknown, and no treatment has been successful.", "contents": "Subacute sensory neuropathy: a remote effect of carcinoma. Seven patients with subacute sensory neuropathy are described and the findings in 29 previously reported patients are reviewed. The presence of this characteristic neurological disorder strongly suggests an accompanying neoplasm. Five of 7 patients had cancer, and 4 died. Autopsy was performed on 3, and pathological analysis revealed inflammation and degeneration of dorsal root ganglia and degeneration of posterior roots and posterior columns of the spinal cord. The dorsal root ganglion was biopsied in 4 patients and showed similar inflammatory lesions. Electron microscopical studies showed inflammation and neuronal degeneration. No viral particles were seen. Viral cultures of the biopsied ganglia from 4 patients were negative. Antineuronal antibodies were not detected in 2 patients. The cause of this syndrome is unknown, and no treatment has been successful."}
{"id": "PMID:197873", "title": "[Radio-receptor assay for thyrotropin releasing hormone (author's transl)].", "content": "The high affinity receptor for TRH of a rat pituitary GH3 strain in culture (Km: 4 X 10(-9) M) was found suitable to design a radio-receptor assay for TRH. Attached GH3 cells were incubated for 30 min at 37 degrees C in presence of a tracer amount of 3H-TRH (200 pg/ml, 0.54 nM) and increasing quantities of cold synthetic TRH. After extensive washings, the radioactivity associated with the cells was counted, and the log-logit transformation was applied to the results expressed as % binding (100%: binding in absence of unlabelled TRH). The standard curve is linear between 200 pg/ml and 5 ng/ml TRH. Hypothalamic or thyroid hormones were tested for their competitive effect with 3H-TRH towards the GH3 cells receptor. None of them interfered. TRH analogs were also assayed for their competition with TRH towards the receptor. Only compounds methylated on Prolineamide or Histidine could compete with TRH, but these derivatives have never been shown to occur in vivo. Because of this high specificity, we applied this radioreceptor assay to biological samples, once extracted by acidic methanol and purified by CMC column (following a technics designed by K Bauer, Berlin).", "contents": "[Radio-receptor assay for thyrotropin releasing hormone (author's transl)]. The high affinity receptor for TRH of a rat pituitary GH3 strain in culture (Km: 4 X 10(-9) M) was found suitable to design a radio-receptor assay for TRH. Attached GH3 cells were incubated for 30 min at 37 degrees C in presence of a tracer amount of 3H-TRH (200 pg/ml, 0.54 nM) and increasing quantities of cold synthetic TRH. After extensive washings, the radioactivity associated with the cells was counted, and the log-logit transformation was applied to the results expressed as % binding (100%: binding in absence of unlabelled TRH). The standard curve is linear between 200 pg/ml and 5 ng/ml TRH. Hypothalamic or thyroid hormones were tested for their competitive effect with 3H-TRH towards the GH3 cells receptor. None of them interfered. TRH analogs were also assayed for their competition with TRH towards the receptor. Only compounds methylated on Prolineamide or Histidine could compete with TRH, but these derivatives have never been shown to occur in vivo. Because of this high specificity, we applied this radioreceptor assay to biological samples, once extracted by acidic methanol and purified by CMC column (following a technics designed by K Bauer, Berlin)."}
{"id": "PMID:197881", "title": "Polymyxin and related peptide antibiotics.", "content": "The general mechanism for the antibiotic activities of the polymyxins and octapeptins has been elucidated by research using a broad range of experimental techniques. However, this phenomenon has not been described in detailed molecular terms, and this must be one of the major goals for future research in this area. Since 1947, when polymyxin was first isolated, there have been tremendous advances in our knowledge of membrane structure. The application of biophysical technology such as NMR, ESR, fluorescence spectroscopy, differential scanning calorimetry, and electron microscopy has been particularly valuable for studying model and biological membrane structures. It is these techniques which will provide a detailed molecular mechanism for the effects of these peptide antibiotics on membrane structure. In addition, the large number of antibiotic derivatives available should be exploited more extensively for structure-function correlations. The ultimate goal is to correlate the biological properties of these peptides with their effects on the physical properties of membranes and to rationalize these events in terms of lipid-peptide interactions.", "contents": "Polymyxin and related peptide antibiotics. The general mechanism for the antibiotic activities of the polymyxins and octapeptins has been elucidated by research using a broad range of experimental techniques. However, this phenomenon has not been described in detailed molecular terms, and this must be one of the major goals for future research in this area. Since 1947, when polymyxin was first isolated, there have been tremendous advances in our knowledge of membrane structure. The application of biophysical technology such as NMR, ESR, fluorescence spectroscopy, differential scanning calorimetry, and electron microscopy has been particularly valuable for studying model and biological membrane structures. It is these techniques which will provide a detailed molecular mechanism for the effects of these peptide antibiotics on membrane structure. In addition, the large number of antibiotic derivatives available should be exploited more extensively for structure-function correlations. The ultimate goal is to correlate the biological properties of these peptides with their effects on the physical properties of membranes and to rationalize these events in terms of lipid-peptide interactions."}
{"id": "PMID:197885", "title": "Specificity of isoniazid on growth inhibition and competition for an oxidized nicotinamide adenine dinucleotide regulatory site on the electron transport pathway in Mycobacterium phlei.", "content": "The mechanism of action of isoniazid (INH) on saprophytic and atypical mycobacteria is thought to be different from that on Mycobacterium tuberculosis because higher concentrations are required to be effective in these species. In this investigation, M. phlei was inhibited by INH at a concentration of 25 mug/ml. Benzoic acid hydrazide (BZH) and nicotinic acid hydrazide (NAH) were inhibitory at levels of 300 and 500 mug/ml, respectively. Inhibition by these compounds was not inoculum dependent. An isolated M. phlei mutant resistant to 100 mug of INH per ml (Inh(r)) was inhibited by INH only at concentrations about equal to those inhibitory for BZH and NAH. When NAH and BZH were below their minimal inhibitory concentrations, INH inhibition was antagonized. Hence, there appears to be a single target site for INH in mycobacteria with different affinities for various hydrazide analogs of INH. The increased inhibitory levels required for the atypical and saprophytic species are due to a decreased affinity of the target site for INH in these species. INH also inhibited both the oxidized nicotinamide adenine dinucleotide (NAD(+)) and adenosine 5'-monophosphate stimulation of reduced NAD (NADH) oxidase activity associated with the M. phlei and M. tuberculosis H(37)R(a) electron transport particles. INH did not reverse the NAD(+) stimulation of oxidase activity in the Inh(r) strain of M. phlei. No direct inhibitory effect of INH on NADH oxidase activity was observed. Incubation of M. phlei electron transport particles at 0 degrees C with INH resulted in a dramatic loss of oxidase activity which could have been prevented if NAD(+) were present. However, INH had no effect upon the NADH oxidase when stored with electron transport particles isolated from the Inh(r) strain. Therefore, INH inhibition of regulation and/or stabilization of the electron transport pathway by NAD(+) or adenosine 5'-monophosphate may account, in part, for the lethal action of the drug on mycobacteria.", "contents": "Specificity of isoniazid on growth inhibition and competition for an oxidized nicotinamide adenine dinucleotide regulatory site on the electron transport pathway in Mycobacterium phlei. The mechanism of action of isoniazid (INH) on saprophytic and atypical mycobacteria is thought to be different from that on Mycobacterium tuberculosis because higher concentrations are required to be effective in these species. In this investigation, M. phlei was inhibited by INH at a concentration of 25 mug/ml. Benzoic acid hydrazide (BZH) and nicotinic acid hydrazide (NAH) were inhibitory at levels of 300 and 500 mug/ml, respectively. Inhibition by these compounds was not inoculum dependent. An isolated M. phlei mutant resistant to 100 mug of INH per ml (Inh(r)) was inhibited by INH only at concentrations about equal to those inhibitory for BZH and NAH. When NAH and BZH were below their minimal inhibitory concentrations, INH inhibition was antagonized. Hence, there appears to be a single target site for INH in mycobacteria with different affinities for various hydrazide analogs of INH. The increased inhibitory levels required for the atypical and saprophytic species are due to a decreased affinity of the target site for INH in these species. INH also inhibited both the oxidized nicotinamide adenine dinucleotide (NAD(+)) and adenosine 5'-monophosphate stimulation of reduced NAD (NADH) oxidase activity associated with the M. phlei and M. tuberculosis H(37)R(a) electron transport particles. INH did not reverse the NAD(+) stimulation of oxidase activity in the Inh(r) strain of M. phlei. No direct inhibitory effect of INH on NADH oxidase activity was observed. Incubation of M. phlei electron transport particles at 0 degrees C with INH resulted in a dramatic loss of oxidase activity which could have been prevented if NAD(+) were present. However, INH had no effect upon the NADH oxidase when stored with electron transport particles isolated from the Inh(r) strain. Therefore, INH inhibition of regulation and/or stabilization of the electron transport pathway by NAD(+) or adenosine 5'-monophosphate may account, in part, for the lethal action of the drug on mycobacteria."}
{"id": "PMID:197886", "title": "Antiviral activity of arabinosylthymine in herpesviral replication: mechanism of action in vivo and in vitro.", "content": "1-beta-d-Arabinofuranosylthymine (ara-T), a metabolite of the sponge Tethya crypta, has shown selective activity against herpes simplex virus (HSV) replication (G. A. Gentry and J. F. Aswell, Virology 65:294-296, 1975). Analysis of HSV-infected and uninfected cell lysates by CsCl isopycnic centrifugation showed that ara-T blocked the incorporation of [(3)H]hypoxanthine into viral deoxyribonucleic acid and, to a large extent, into host deoxyribonucleic acid of infected (but not uninfected) cells. Additional experiments with [gamma-(32)P]adenosine 5'-triphosphate as a radiophosphate donor demonstrated that ara-T is phosphorylated by extracts of HSV-infected BHK cells and not by those of uninfected cells. At an ara-T concentration that almost completely inhibited the growth of LM cells, which had been transformed to a pyrimidine deoxyribonucleoside kinase(+) (dPyK(+)) phenotype by ultraviolet-inactivated HSV-1, the growth of uninfected LM cells was not affected. These results indicate that the viral dPyK is responsible for the selective antiviral activity of ara-T. This conclusion was further supported by experiments that showed that the replication of a variety of dPyK(-) mutants of HSV-1 and HSV-2 were not affected by ara-T and that ara-T inhibited the phosphorylation of deoxycytidine and deoxythymidine by HSV-1 dPyK, but not by host deoxycytidine and deoxythymidine kinases, respectively. Ara-T also selectively inhibited the replication of equine herpesvirus type 1 (EHV-1) in vitro and was effective against EHV-1 infection in vivo in hamsters. Further, EHV-1 was inhibited by ara-T and by bromodeoxyuridine in LM cells lacking a cytosol thymidine kinase, suggesting that EHV-1 induces a dPyK. Finally, spectrophotometric assay for thymine suggested that ara-T is not a substrate for nucleoside phosphorylase of hamster liver, and a microbiological assay indicated that substantial amounts of ara-T were excreted in the urine of uninfected hamsters that had received a single injection of 5 mg of ara-T, the amount given in each injection in the in vivo experiments with EHV-1.", "contents": "Antiviral activity of arabinosylthymine in herpesviral replication: mechanism of action in vivo and in vitro. 1-beta-d-Arabinofuranosylthymine (ara-T), a metabolite of the sponge Tethya crypta, has shown selective activity against herpes simplex virus (HSV) replication (G. A. Gentry and J. F. Aswell, Virology 65:294-296, 1975). Analysis of HSV-infected and uninfected cell lysates by CsCl isopycnic centrifugation showed that ara-T blocked the incorporation of [(3)H]hypoxanthine into viral deoxyribonucleic acid and, to a large extent, into host deoxyribonucleic acid of infected (but not uninfected) cells. Additional experiments with [gamma-(32)P]adenosine 5'-triphosphate as a radiophosphate donor demonstrated that ara-T is phosphorylated by extracts of HSV-infected BHK cells and not by those of uninfected cells. At an ara-T concentration that almost completely inhibited the growth of LM cells, which had been transformed to a pyrimidine deoxyribonucleoside kinase(+) (dPyK(+)) phenotype by ultraviolet-inactivated HSV-1, the growth of uninfected LM cells was not affected. These results indicate that the viral dPyK is responsible for the selective antiviral activity of ara-T. This conclusion was further supported by experiments that showed that the replication of a variety of dPyK(-) mutants of HSV-1 and HSV-2 were not affected by ara-T and that ara-T inhibited the phosphorylation of deoxycytidine and deoxythymidine by HSV-1 dPyK, but not by host deoxycytidine and deoxythymidine kinases, respectively. Ara-T also selectively inhibited the replication of equine herpesvirus type 1 (EHV-1) in vitro and was effective against EHV-1 infection in vivo in hamsters. Further, EHV-1 was inhibited by ara-T and by bromodeoxyuridine in LM cells lacking a cytosol thymidine kinase, suggesting that EHV-1 induces a dPyK. Finally, spectrophotometric assay for thymine suggested that ara-T is not a substrate for nucleoside phosphorylase of hamster liver, and a microbiological assay indicated that substantial amounts of ara-T were excreted in the urine of uninfected hamsters that had received a single injection of 5 mg of ara-T, the amount given in each injection in the in vivo experiments with EHV-1."}
{"id": "PMID:197898", "title": "Hypothalamic hypopituitarism after pituitary apoplexy in acromegaly.", "content": "Pituitary apoplexy in acromegaly is an uncommon event having been recorded approximately 30 times in the English literature. This report records two additional cases that included growth hormone measurements and an assessment of pituitary function. The apoplectic event developed spontaneously in one, and in the other it developed within two weeks of completing a course of radiotherapy to the pituitary gland. Autocure of the acromegaly was apparent. Basal levels of growth hormone were in the normal range but failed to change with provocative stimuli. Luteinizing hormone and follicle-stimulating hormone titers, although detectable, were inappropriately low for the degree of hypogonadism. Pituitary insufficiency was associated with a significant thyroid-stimulating hormone response to protirelin in one patient tested. It is suggested that these experiments of nature lend credence to the proposal that the hypothalamus may play a critical role in the perpetuation of growth hormone hypersecretion in some patients with acromegaly.", "contents": "Hypothalamic hypopituitarism after pituitary apoplexy in acromegaly. Pituitary apoplexy in acromegaly is an uncommon event having been recorded approximately 30 times in the English literature. This report records two additional cases that included growth hormone measurements and an assessment of pituitary function. The apoplectic event developed spontaneously in one, and in the other it developed within two weeks of completing a course of radiotherapy to the pituitary gland. Autocure of the acromegaly was apparent. Basal levels of growth hormone were in the normal range but failed to change with provocative stimuli. Luteinizing hormone and follicle-stimulating hormone titers, although detectable, were inappropriately low for the degree of hypogonadism. Pituitary insufficiency was associated with a significant thyroid-stimulating hormone response to protirelin in one patient tested. It is suggested that these experiments of nature lend credence to the proposal that the hypothalamus may play a critical role in the perpetuation of growth hormone hypersecretion in some patients with acromegaly."}
{"id": "PMID:197899", "title": "[Relationship between the limbic system and gonadal function. 2. Quantifiable prepuberal differentiation of medial cortical amygdaloid nuclei].", "content": "In juvenile female rats beteen the 21st and 26th days of age, the neurons of the medial and cortical amygdaloid nuclei undergo a highly significant karyovolumetrically measurable activation which, however, partially declines almost immediately. Such prepuberal variation of activity was found to be correlated with age-dependent effects of direct interventions with these nuclear regions upon the hypothalamy-pituitary-gonadal axis, e.g. implantation of oestradiol benzoate, stimulation or lesioning. This basically, is a quantitatibe-morphological confirmation of an assumption that had been derived earlier from experimental studies, according to which the mediocortical part of the amygdala undergoes in the prepuberal period a functional muteration or differentiation which is specific and related to puberty and gonadal functions (D\u00f6cke, 1976a, b; D\u00f6cke et al., 1976).", "contents": "[Relationship between the limbic system and gonadal function. 2. Quantifiable prepuberal differentiation of medial cortical amygdaloid nuclei]. In juvenile female rats beteen the 21st and 26th days of age, the neurons of the medial and cortical amygdaloid nuclei undergo a highly significant karyovolumetrically measurable activation which, however, partially declines almost immediately. Such prepuberal variation of activity was found to be correlated with age-dependent effects of direct interventions with these nuclear regions upon the hypothalamy-pituitary-gonadal axis, e.g. implantation of oestradiol benzoate, stimulation or lesioning. This basically, is a quantitatibe-morphological confirmation of an assumption that had been derived earlier from experimental studies, according to which the mediocortical part of the amygdala undergoes in the prepuberal period a functional muteration or differentiation which is specific and related to puberty and gonadal functions (D\u00f6cke, 1976a, b; D\u00f6cke et al., 1976)."}
{"id": "PMID:197900", "title": "Follow-up of adolescents treated in a psychiatric hospital. Predictors of outcome.", "content": "In the context of a long-term follow-up of 60 hospitalized adolescent psychiatric patients (26 months to four years after discharge), we examined correlates of outcome. The variables were as follows: (1) severity of psychopathology; (2) onset of symptomatology (process or reactive); (3) type of hospital treatment termination; (4) continuation of individual psychotherapy following discharge; (5) physically destructive behavior before hospitalization; and (6) energy level. Follow-up was by personal clinical interview exploring the expatient's current living conditions, peer relationships, current psychopathology and drug or alcohol use, legal difficulties, academic and work functioning, subjective contentment, and plans for the future. An evaluation was also obtained from parents and/or spouse. Statistical analyses of the interrelationships among the predictor variables and outcome demonstrated the importance of a multivariate approach.", "contents": "Follow-up of adolescents treated in a psychiatric hospital. Predictors of outcome. In the context of a long-term follow-up of 60 hospitalized adolescent psychiatric patients (26 months to four years after discharge), we examined correlates of outcome. The variables were as follows: (1) severity of psychopathology; (2) onset of symptomatology (process or reactive); (3) type of hospital treatment termination; (4) continuation of individual psychotherapy following discharge; (5) physically destructive behavior before hospitalization; and (6) energy level. Follow-up was by personal clinical interview exploring the expatient's current living conditions, peer relationships, current psychopathology and drug or alcohol use, legal difficulties, academic and work functioning, subjective contentment, and plans for the future. An evaluation was also obtained from parents and/or spouse. Statistical analyses of the interrelationships among the predictor variables and outcome demonstrated the importance of a multivariate approach."}
{"id": "PMID:197901", "title": "News on psychiatric research. Two recent advisory reports.", "content": "Two recent reports have rendered psychiatric research a great service in acknowledging the serious problem under which this research has been laboring and by making recommendations for improved functioning. The President's Biomedical Research Panel is the first high-level government body to take note of what it has felicitously called the \"precipitous decline\" in research support of the National Institute of Mental Health. Its recommendations of a greatly strengthened research advisory capability of the Alcohol, Drug Abuse, and Mental Health Administration Institutes effectively complements its recommendations for increased funding of these institutes. The Committee on Biomedical Research in the Veterans Administration, noting the \"severely limited\" support of research on the VA's massive problem of mental illness, proposed a series of specific recommendations for an improved and expanded research effort.", "contents": "News on psychiatric research. Two recent advisory reports. Two recent reports have rendered psychiatric research a great service in acknowledging the serious problem under which this research has been laboring and by making recommendations for improved functioning. The President's Biomedical Research Panel is the first high-level government body to take note of what it has felicitously called the \"precipitous decline\" in research support of the National Institute of Mental Health. Its recommendations of a greatly strengthened research advisory capability of the Alcohol, Drug Abuse, and Mental Health Administration Institutes effectively complements its recommendations for increased funding of these institutes. The Committee on Biomedical Research in the Veterans Administration, noting the \"severely limited\" support of research on the VA's massive problem of mental illness, proposed a series of specific recommendations for an improved and expanded research effort."}
{"id": "PMID:197903", "title": "Wilms' tumor with acute abdominal pain.", "content": "Acute abdominal pain is the presenting manifestation in approximately 30% of all patients with Willms' tumor. In a small proportion of these patients this pain is significant enough to engender a diagnosis of an acute surgical abdomen. Six of 38 patients with Wilms' tumors treated between the years 1965 and 1975 at the Shands Teaching Hospital of the University of Florida Medical Center have had significant pain. Our experience with these patients emphasizes the importance of thoroughly palpating the abdomen of any child with a suspected acute surgical condition, following induction of anesthesia and prior to initiating the operation. In the absence of any evidence of an acute surgical problem at the time of the exploratory laparotomy, it is also imperative that a careful intra-abdominal examination be performed to exclude the presence of conditions, such as Wilms tumor of the kidney, that may occasionally present in this manner.", "contents": "Wilms' tumor with acute abdominal pain. Acute abdominal pain is the presenting manifestation in approximately 30% of all patients with Willms' tumor. In a small proportion of these patients this pain is significant enough to engender a diagnosis of an acute surgical abdomen. Six of 38 patients with Wilms' tumors treated between the years 1965 and 1975 at the Shands Teaching Hospital of the University of Florida Medical Center have had significant pain. Our experience with these patients emphasizes the importance of thoroughly palpating the abdomen of any child with a suspected acute surgical condition, following induction of anesthesia and prior to initiating the operation. In the absence of any evidence of an acute surgical problem at the time of the exploratory laparotomy, it is also imperative that a careful intra-abdominal examination be performed to exclude the presence of conditions, such as Wilms tumor of the kidney, that may occasionally present in this manner."}
{"id": "PMID:197904", "title": "[Chromatin fibril. Structure and relationship to the nuclear membrane].", "content": "Literature for the recent years on chromatin fibrilla structure is reviewed in the work. Ultrastructural and molecular organization of the elementary chromatin subunits--nucleosomes, discovered in 1974 is discussed and their relation to other discrete chromatin particles is analyzed. The author represents his own data on electron microscopic studies of the cell nucleus after certain experimental effect demonstrating a complex structure of chromatin particles. The scheme of chromatin fibrilla structure is given; morphologic and functional aspects of its connection with the nuclear membrane are considered.", "contents": "[Chromatin fibril. Structure and relationship to the nuclear membrane]. Literature for the recent years on chromatin fibrilla structure is reviewed in the work. Ultrastructural and molecular organization of the elementary chromatin subunits--nucleosomes, discovered in 1974 is discussed and their relation to other discrete chromatin particles is analyzed. The author represents his own data on electron microscopic studies of the cell nucleus after certain experimental effect demonstrating a complex structure of chromatin particles. The scheme of chromatin fibrilla structure is given; morphologic and functional aspects of its connection with the nuclear membrane are considered."}
{"id": "PMID:197905", "title": "[Quantitative histoenzymologic characteristics of the human submandibular salivary glands].", "content": "Quantitative activity of oxidative-reductive and hydrolytic enzymes obtained during operation was investigated in different parts of the human submandibular salivary glands. Quantitative estimation of enzymic activity was done by photometry of the negatives prepared on MY-phi-6. Comparative examination of enzymatic activity made it possible to state that according to the peculiarities of metabolic processes, the cells of striated and intralobular secreting ducts are similar to the cells of the secreting terminal parts. A high activity of NADP-diaphorase, G-6-PhDG and acid phosphatase in the epithelium of the secreting ducts, and parallelism, stated between histoenzymatic and morphologic criteria of functional activity proved the participation of these structural-functional units in secret-producing processes. A high activity of NAK-diaphorase, LDG and acid phosphatase in all the parts and in the secreting ducts system, in particular, ensures, besides the processes of protein secret formation, an active transport of natrium and potassium, formation of final saliva and its discharge.", "contents": "[Quantitative histoenzymologic characteristics of the human submandibular salivary glands]. Quantitative activity of oxidative-reductive and hydrolytic enzymes obtained during operation was investigated in different parts of the human submandibular salivary glands. Quantitative estimation of enzymic activity was done by photometry of the negatives prepared on MY-phi-6. Comparative examination of enzymatic activity made it possible to state that according to the peculiarities of metabolic processes, the cells of striated and intralobular secreting ducts are similar to the cells of the secreting terminal parts. A high activity of NADP-diaphorase, G-6-PhDG and acid phosphatase in the epithelium of the secreting ducts, and parallelism, stated between histoenzymatic and morphologic criteria of functional activity proved the participation of these structural-functional units in secret-producing processes. A high activity of NAK-diaphorase, LDG and acid phosphatase in all the parts and in the secreting ducts system, in particular, ensures, besides the processes of protein secret formation, an active transport of natrium and potassium, formation of final saliva and its discharge."}
{"id": "PMID:197906", "title": "[Differential diagnosis of ulcerogenic tumors, insulomas and carcinoid tumors].", "content": "The ultrastructural intactness of secretory granules in the cells of ulcerogenic tumours, insuloma and carcinoid were demonstrated in the operation material embedded in paraffin. Feature of similarity and differences in the tumours under study with respect to the size and shape, and distribution of granules in the cells were established.", "contents": "[Differential diagnosis of ulcerogenic tumors, insulomas and carcinoid tumors]. The ultrastructural intactness of secretory granules in the cells of ulcerogenic tumours, insuloma and carcinoid were demonstrated in the operation material embedded in paraffin. Feature of similarity and differences in the tumours under study with respect to the size and shape, and distribution of granules in the cells were established."}
{"id": "PMID:197907", "title": "[Effect of drugs on electroclinical types of epileptic seizures in Lennox-Gastaut syndrome].", "content": "The therapeutics results with the use of different drugs (diazepam, nitrazepam, clonazepam, diphenylhydantoin, barbiturates--phenobarbital and primidone--, sodium dipropylacetate and ACTH) in twenty-nine patients with Lennox--Gastaut syndrome are carefully analysed. The effect of each drug on seizures (tonic, tonic-clonic, clonic, myoclonic or myoclonic-atonic, atonic and atypical absences) during the first month of each treatment is discussed. The \"specific\" use of each drug on the various forms of epileptic seizures is determined and the possibility of crisis control with reduction of the drugs dosage is verified.", "contents": "[Effect of drugs on electroclinical types of epileptic seizures in Lennox-Gastaut syndrome]. The therapeutics results with the use of different drugs (diazepam, nitrazepam, clonazepam, diphenylhydantoin, barbiturates--phenobarbital and primidone--, sodium dipropylacetate and ACTH) in twenty-nine patients with Lennox--Gastaut syndrome are carefully analysed. The effect of each drug on seizures (tonic, tonic-clonic, clonic, myoclonic or myoclonic-atonic, atonic and atypical absences) during the first month of each treatment is discussed. The \"specific\" use of each drug on the various forms of epileptic seizures is determined and the possibility of crisis control with reduction of the drugs dosage is verified."}
{"id": "PMID:197908", "title": "Antibiotic therapy of experimental Pseudomonas keratitis in guinea pigs.", "content": "Antibiotic therapy of experimental Pseudomonas keratitis was evaluated quantitatively by determining numbers of viable bacteria in the cornea of guinea pigs. Topically applied carbenicillin disodium, gentamicin sulfate, and tobramycin sulfate were often significantly more effective than topically applied polymyxin B sulfate. Intramuscular therapy with tobramycin was as effective as topical therapy, and the results exhibited less variability. Topical tobramycin every 30 minutes was significantly more effective than topical therapy every 60 minutes. No combination of antibiotics was significantly better than a single effective drug. The concentration of tobramycin in the aqueous correlated  more closely to therapeutic efficacy than did the concentration in the cornea. Although all antibiotics reduced numbers of bacteria in the cornea by more than 99% in the first 24 hours of therapy, none was able to sterilize the cornea in four additional days of continuous therapy. Persistence of organisms despite apparently adequate topical therapy may explain some reported cases of relapse in humans.", "contents": "Antibiotic therapy of experimental Pseudomonas keratitis in guinea pigs. Antibiotic therapy of experimental Pseudomonas keratitis was evaluated quantitatively by determining numbers of viable bacteria in the cornea of guinea pigs. Topically applied carbenicillin disodium, gentamicin sulfate, and tobramycin sulfate were often significantly more effective than topically applied polymyxin B sulfate. Intramuscular therapy with tobramycin was as effective as topical therapy, and the results exhibited less variability. Topical tobramycin every 30 minutes was significantly more effective than topical therapy every 60 minutes. No combination of antibiotics was significantly better than a single effective drug. The concentration of tobramycin in the aqueous correlated  more closely to therapeutic efficacy than did the concentration in the cornea. Although all antibiotics reduced numbers of bacteria in the cornea by more than 99% in the first 24 hours of therapy, none was able to sterilize the cornea in four additional days of continuous therapy. Persistence of organisms despite apparently adequate topical therapy may explain some reported cases of relapse in humans."}
{"id": "PMID:197909", "title": "Laryngeal carcinoma associated with multiple additional primary tumors. Immunologic studies.", "content": "Four malignant tumors and one benign in a 76-year-old man appeared. Three of the neoplasms were in the respiratory system, and one was a bladder carcinoma; all were linked to heavy smoking habits. The patient underwent immunologic investigations consisting of in vivo testing for cutaneous reactivity, in vitro lymphocyte blastogenesis studies, T- and B-cell level studies, and serum immunoglobulin level studies. The studies have demonstrated anergy to recall antigens, decreased lymphocyte responses to phytohemagglutinin, and low levels of peripheral T-lymphocytes. The serum immunoglobulins were at the upper limit of the normal. The relationship between the patient's immunologic status and the occurrence of multiple primary neoplasms is discussed.", "contents": "Laryngeal carcinoma associated with multiple additional primary tumors. Immunologic studies. Four malignant tumors and one benign in a 76-year-old man appeared. Three of the neoplasms were in the respiratory system, and one was a bladder carcinoma; all were linked to heavy smoking habits. The patient underwent immunologic investigations consisting of in vivo testing for cutaneous reactivity, in vitro lymphocyte blastogenesis studies, T- and B-cell level studies, and serum immunoglobulin level studies. The studies have demonstrated anergy to recall antigens, decreased lymphocyte responses to phytohemagglutinin, and low levels of peripheral T-lymphocytes. The serum immunoglobulins were at the upper limit of the normal. The relationship between the patient's immunologic status and the occurrence of multiple primary neoplasms is discussed."}
{"id": "PMID:197910", "title": "Juvenile nasopharyngeal angiofibroma. An unusual presentation as an oral mass.", "content": "Although juvenile nasopharyngeal angiofibroma (JNAF) usually presents as a mass in the nasopharynx, the primary manifestation may, in rare instances, occur intraorally. We observed such a case in a 12-year-old boy. The clinical finding of hemorrhage from the nasopharynx or contiguous areas in a male adolescent is an important diagnostic clue which should alert the clinician to the possibility of JNAF as the underlying cause.", "contents": "Juvenile nasopharyngeal angiofibroma. An unusual presentation as an oral mass. Although juvenile nasopharyngeal angiofibroma (JNAF) usually presents as a mass in the nasopharynx, the primary manifestation may, in rare instances, occur intraorally. We observed such a case in a 12-year-old boy. The clinical finding of hemorrhage from the nasopharynx or contiguous areas in a male adolescent is an important diagnostic clue which should alert the clinician to the possibility of JNAF as the underlying cause."}
{"id": "PMID:197915", "title": "Sarcoidosis--1977.", "content": "Sarcoidosis is defined as a multisystem disorder characterised by the finding of epithelioid cell granulomas in more than one system. Diagnosis is aided by the use of the Kveim Siltzbach skin test and the development of an \"in vitro\" Kmif test is discussed. Despite extensive researches the causative agent(s) remains unknown. The granulomas, morphologically, on light and electron microscopy and histochemistry may be indistinguishable from those caused by known agents. Inclusion bodies are also non specific. Central necrosis is rare, and can be usually distinguished from caseation. The close relationship between the monocyte derived, epithelioid cells and lymphocytes is emphasised. Evidence is accumulating that epithelioid cells in sarcoid type granulomas are primarily synthesising rather than phagocytic cells. The products are considered to be mucoglycoproteins and may have both local and systemic actions. Locally it is suggested that the products may be lymphokines which react with associated thymic derived (T) lymphocytes and mononuclear cells and thus play a role in perpetuating the granulomas. Epithelioid cells may also be a source of circulating T lymphocyte function depressants. It has further been suggested that epitheloid cells are the source of the raised angiotensin converting enzyme found in sarcoid sera. Study of epithelioid cell granulomas in sarcoidosis, despite the disappointing lack of evidence of a causative sarcoid agent(s), is thus of considerable interest in furthering knowledge of many diseases characterised by these curious cellular foci.", "contents": "Sarcoidosis--1977. Sarcoidosis is defined as a multisystem disorder characterised by the finding of epithelioid cell granulomas in more than one system. Diagnosis is aided by the use of the Kveim Siltzbach skin test and the development of an \"in vitro\" Kmif test is discussed. Despite extensive researches the causative agent(s) remains unknown. The granulomas, morphologically, on light and electron microscopy and histochemistry may be indistinguishable from those caused by known agents. Inclusion bodies are also non specific. Central necrosis is rare, and can be usually distinguished from caseation. The close relationship between the monocyte derived, epithelioid cells and lymphocytes is emphasised. Evidence is accumulating that epithelioid cells in sarcoid type granulomas are primarily synthesising rather than phagocytic cells. The products are considered to be mucoglycoproteins and may have both local and systemic actions. Locally it is suggested that the products may be lymphokines which react with associated thymic derived (T) lymphocytes and mononuclear cells and thus play a role in perpetuating the granulomas. Epithelioid cells may also be a source of circulating T lymphocyte function depressants. It has further been suggested that epitheloid cells are the source of the raised angiotensin converting enzyme found in sarcoid sera. Study of epithelioid cell granulomas in sarcoidosis, despite the disappointing lack of evidence of a causative sarcoid agent(s), is thus of considerable interest in furthering knowledge of many diseases characterised by these curious cellular foci."}
{"id": "PMID:197916", "title": "Partial purification, properties and regulation of inosine 5'phosphate dehydrogenase in normal and malignant rat tissues.", "content": "IMP dehydrogenase (EC 1.2.1.14) was purified 180-fold from rat liver and from the transplantable rat hepatoma 3924A. The enzymes from the two sources were apparently identical; they exhibited hyperbolic saturation kinetics and an ordered, sequential mechanism, and were subject to inhibition by a number of purine nucleotides. Km values for the substrates, IMP and NAD+, were 12 and 24 micrometer respectively. IMP dehydrogenase activity in a spectrum of rat hepatomas was increased, relative to normal liver, by 2.5--13-fold; these increases correlated with tumour growth rate. Activity in two rat kidney tumours was increased 3-fold relative to that in normal renal cortex; control of activity of this enzyme is apparently altered in neoplastic cells. After partial hepatectomy, IMP dehydrogenase activity began to rise 6 h after operation, reaching a peak of 580% of normal activity by 18 h. Activity in neonatal liver, however, was only slightly higher than that in the adult. Organ-distribution studies showed highest enzyme activities in spleen and thymus. In livers of rats starved for 3 days, where all enzymes, except those involved in gluconeogenesis, showed decreased activity IMP dehydrogenase activity was increased; this change was accompanied by a rise in hepatic GTP concentrations. It is concluded that IMP dehydrogenase is a key enzyme in the regulation of GTP production, and thus involved in regulation of nucleic acid biosynthesis. The increased activity of IMP dehydrogenase in liver of starved rats may be related to the requirements for GTP for gluconeogenesis.", "contents": "Partial purification, properties and regulation of inosine 5'phosphate dehydrogenase in normal and malignant rat tissues. IMP dehydrogenase (EC 1.2.1.14) was purified 180-fold from rat liver and from the transplantable rat hepatoma 3924A. The enzymes from the two sources were apparently identical; they exhibited hyperbolic saturation kinetics and an ordered, sequential mechanism, and were subject to inhibition by a number of purine nucleotides. Km values for the substrates, IMP and NAD+, were 12 and 24 micrometer respectively. IMP dehydrogenase activity in a spectrum of rat hepatomas was increased, relative to normal liver, by 2.5--13-fold; these increases correlated with tumour growth rate. Activity in two rat kidney tumours was increased 3-fold relative to that in normal renal cortex; control of activity of this enzyme is apparently altered in neoplastic cells. After partial hepatectomy, IMP dehydrogenase activity began to rise 6 h after operation, reaching a peak of 580% of normal activity by 18 h. Activity in neonatal liver, however, was only slightly higher than that in the adult. Organ-distribution studies showed highest enzyme activities in spleen and thymus. In livers of rats starved for 3 days, where all enzymes, except those involved in gluconeogenesis, showed decreased activity IMP dehydrogenase activity was increased; this change was accompanied by a rise in hepatic GTP concentrations. It is concluded that IMP dehydrogenase is a key enzyme in the regulation of GTP production, and thus involved in regulation of nucleic acid biosynthesis. The increased activity of IMP dehydrogenase in liver of starved rats may be related to the requirements for GTP for gluconeogenesis."}
{"id": "PMID:197917", "title": "Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation.", "content": "1. Cathepsin B, a tissue (lysosomal) proteinase, and two humoral proteinases, plasmin and kallikrein, activate the latent collagenase ('procollagenase') which is released by mouse bone explants in culture. Other lysosomal proteinases (carboxypeptidase B, cathepsin C and D) and thrombin did not activate the procollagenase. Dialysis of the culture fluids against 3M-NaSCN at 4 degrees C and, for some culture fluids, prolonged preincubation at 25 degrees C also caused the activation of procollagenase. 2. In all these cases, activation of procollagenase involved at least two successive steps: the activation of an endogenous latent activator present in the culture fluids and the activation of procollagenase itself. 3. An assay method was developed for the endogenous activator. Human serum, bovine serum albumin, casein and cysteine inhibited the endogenous activator at concentrations that did not influence the collagenase activity. N-Ethylmaleimide and 4-hydroxy-mercuribenzoate stimulated the endogenous activator, but iodoacetate had no effect. 4. It is proposed that cathepsin B, kallikrein and plasmin may play a role in the physiological activation of latent collagenase and thus initiate degradation of collagen in vivo. This may occur whatever the molecular nature of procollagenase (zymogen or enzyme-inhibitor complex) might be.", "contents": "Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation. 1. Cathepsin B, a tissue (lysosomal) proteinase, and two humoral proteinases, plasmin and kallikrein, activate the latent collagenase ('procollagenase') which is released by mouse bone explants in culture. Other lysosomal proteinases (carboxypeptidase B, cathepsin C and D) and thrombin did not activate the procollagenase. Dialysis of the culture fluids against 3M-NaSCN at 4 degrees C and, for some culture fluids, prolonged preincubation at 25 degrees C also caused the activation of procollagenase. 2. In all these cases, activation of procollagenase involved at least two successive steps: the activation of an endogenous latent activator present in the culture fluids and the activation of procollagenase itself. 3. An assay method was developed for the endogenous activator. Human serum, bovine serum albumin, casein and cysteine inhibited the endogenous activator at concentrations that did not influence the collagenase activity. N-Ethylmaleimide and 4-hydroxy-mercuribenzoate stimulated the endogenous activator, but iodoacetate had no effect. 4. It is proposed that cathepsin B, kallikrein and plasmin may play a role in the physiological activation of latent collagenase and thus initiate degradation of collagen in vivo. This may occur whatever the molecular nature of procollagenase (zymogen or enzyme-inhibitor complex) might be."}
{"id": "PMID:197974", "title": "Hypolipidemic activity of in vitro inhibitors of hepatic and intestinal sn-glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase.", "content": "A number of agents including a series of 1,3-bis (substituted phenoxy)-2-propanones were screened in vitro for their ability to inhibit hepatic and intestinal microsomal sn-glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase. Effective inhibitors reduced in vivo hepatic and intestinal glycerolipid production and with one exception also lowered serum triglyceride levels, suggesting that agents which inhibit potential rate-limiting steps of glycerolipid biosynthesis may be effective hypolipidemic agents. Two compounds, 1-methyl-4-piperidyl bis (p-chlorophenoxy) acetate (Sah 42-348) and 1,3-bis (p-methylphenoxy)-2-propanone were the best inhibitors of glycerolipid biosynthesis and lipid-lowering agents. The lipid-altering effects of both drugs were compared to chlorophenoxyisobutyrate during high fructose intake in rats. Each agent reduced fructose induced glycerolipid biosynthesis and serum triglyceride levels to similar degrees.", "contents": "Hypolipidemic activity of in vitro inhibitors of hepatic and intestinal sn-glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase. A number of agents including a series of 1,3-bis (substituted phenoxy)-2-propanones were screened in vitro for their ability to inhibit hepatic and intestinal microsomal sn-glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase. Effective inhibitors reduced in vivo hepatic and intestinal glycerolipid production and with one exception also lowered serum triglyceride levels, suggesting that agents which inhibit potential rate-limiting steps of glycerolipid biosynthesis may be effective hypolipidemic agents. Two compounds, 1-methyl-4-piperidyl bis (p-chlorophenoxy) acetate (Sah 42-348) and 1,3-bis (p-methylphenoxy)-2-propanone were the best inhibitors of glycerolipid biosynthesis and lipid-lowering agents. The lipid-altering effects of both drugs were compared to chlorophenoxyisobutyrate during high fructose intake in rats. Each agent reduced fructose induced glycerolipid biosynthesis and serum triglyceride levels to similar degrees."}
{"id": "PMID:197975", "title": "Dilute blood clot lysis time and electrophoretic lipoprotein fractions in a population sample of healthy Romanians.", "content": "Serum total lipids and cholesterol, electrophoretically determined lipoprotein concentrations, serum pseudocholinesterase and dilute blood clot lysis time were determined in 630 healthy subjects (287 men and 343 women) aged 20-60, working in the food industry. A high incidence of over-weight was noted ranging from 22.4% in women aged 20-40 to 58.7% in men aged 41-60. Over-weight subjects presenting higher levels of serum cholesterol, total lipids and of the pre-beta electrophoretic fraction also had a higher pseudo-cholinesterase activity and a more delayed clot lysis time than normal-weight subjects matched as to age and sex. When the material was divided into quintiles for pre-beta- and beta-lipoproteins, a highly significant delay of fibrinolysis was noted in the fourth and fifth quintiles for pre-beta-lipoproteins, but no significant changes of lysis time occurred with increasing concentrations of beta-lipoproteins. Possible explanations of the abovementioned findings are briefly discussed.", "contents": "Dilute blood clot lysis time and electrophoretic lipoprotein fractions in a population sample of healthy Romanians. Serum total lipids and cholesterol, electrophoretically determined lipoprotein concentrations, serum pseudocholinesterase and dilute blood clot lysis time were determined in 630 healthy subjects (287 men and 343 women) aged 20-60, working in the food industry. A high incidence of over-weight was noted ranging from 22.4% in women aged 20-40 to 58.7% in men aged 41-60. Over-weight subjects presenting higher levels of serum cholesterol, total lipids and of the pre-beta electrophoretic fraction also had a higher pseudo-cholinesterase activity and a more delayed clot lysis time than normal-weight subjects matched as to age and sex. When the material was divided into quintiles for pre-beta- and beta-lipoproteins, a highly significant delay of fibrinolysis was noted in the fourth and fifth quintiles for pre-beta-lipoproteins, but no significant changes of lysis time occurred with increasing concentrations of beta-lipoproteins. Possible explanations of the abovementioned findings are briefly discussed."}
{"id": "PMID:197972", "title": "Ultrastructural study of avian synovium infected with an arthrotropic reovirus.", "content": "Three-week-old chicks were inoculated via the foot pad with the avian reovirus (strain WVU 2937) that has been proved to be the causative agent in avian viral arthritis. The initial stages of the avian reovirus infection in the synovium of the hock joint were studied by transmission electron microscopy to shed light on the early virus-host relationship of an arthrotropic virus and synovial tissue. At 48 hours postinoculation (PI), coated, partially coated, and uncoated virus particles were seen in a dense lysosome-like inclusion in the cytoplasm of subsynovial fibroblasts. Virus replication was demonstrated in fibroblasts of the subsynovium 4 days PI. Infiltration of leukocytes into the area of the virus replication was noted at the time of virus replication (4 days PI). By the second week of the infection (11 days PI), the subsynovium was heavily infiltrated with lymphocytes and plasma cells, and proliferative changes had occurred in the synovial lining cells.", "contents": "Ultrastructural study of avian synovium infected with an arthrotropic reovirus. Three-week-old chicks were inoculated via the foot pad with the avian reovirus (strain WVU 2937) that has been proved to be the causative agent in avian viral arthritis. The initial stages of the avian reovirus infection in the synovium of the hock joint were studied by transmission electron microscopy to shed light on the early virus-host relationship of an arthrotropic virus and synovial tissue. At 48 hours postinoculation (PI), coated, partially coated, and uncoated virus particles were seen in a dense lysosome-like inclusion in the cytoplasm of subsynovial fibroblasts. Virus replication was demonstrated in fibroblasts of the subsynovium 4 days PI. Infiltration of leukocytes into the area of the virus replication was noted at the time of virus replication (4 days PI). By the second week of the infection (11 days PI), the subsynovium was heavily infiltrated with lymphocytes and plasma cells, and proliferative changes had occurred in the synovial lining cells."}
{"id": "PMID:197976", "title": "Effect of lipoprotein on in vitro synthesis of DNA in aortic tissue.", "content": "(1)Using both an explant system from swine thoracic aorta and an aortic smooth muscle cell culture system, we have investigated the effect of lipoproteins on the synthesis of DNA in the absence of serum or serum derivatives. (2)Chemical and morphological data from both systems confirm that (a) neither VLDL, LDL nor HDL account for any appreciable part of the DNA synthesis activity of whole serum. (b) There is no difference in activity between lipoprotein fractions derived from either normocholesterolemic or hypercholesterolemic serum. (c) The activity resident in whole serum is present largely in the pelleted serum protein fractions and in the soluble resideu. (3) The data suggest that smooth muscle cell proliferation results from the interaction of lipoproteins with other factor(s) in serum.", "contents": "Effect of lipoprotein on in vitro synthesis of DNA in aortic tissue. (1)Using both an explant system from swine thoracic aorta and an aortic smooth muscle cell culture system, we have investigated the effect of lipoproteins on the synthesis of DNA in the absence of serum or serum derivatives. (2)Chemical and morphological data from both systems confirm that (a) neither VLDL, LDL nor HDL account for any appreciable part of the DNA synthesis activity of whole serum. (b) There is no difference in activity between lipoprotein fractions derived from either normocholesterolemic or hypercholesterolemic serum. (c) The activity resident in whole serum is present largely in the pelleted serum protein fractions and in the soluble resideu. (3) The data suggest that smooth muscle cell proliferation results from the interaction of lipoproteins with other factor(s) in serum."}
{"id": "PMID:197977", "title": "Intercellular glycoproteins and low density lipoprotein binding to fibroblasts.", "content": "The interaction of low density lipoprotein (LDL) with solubilized subunits of two purified noncollagenous glycoproteins (A and G) of cartilage matrix have been studied in solution using Sepharose chromatography and at the cell surface using fibroblast monolayers. In the presence of A or G, [125I]-LDL forms aggregates of varying size. After pre-incubation with A or G, under conditions which form highly aggregrated complexes, there is an increase in the binding of LDL to fibroblasts. Mixing with A under conditions which form smaller complexes produced no increase in binding to fibroblasts. It is suggested that interactions of this type may be involved in the pathogenesis of atherosclerosis.", "contents": "Intercellular glycoproteins and low density lipoprotein binding to fibroblasts. The interaction of low density lipoprotein (LDL) with solubilized subunits of two purified noncollagenous glycoproteins (A and G) of cartilage matrix have been studied in solution using Sepharose chromatography and at the cell surface using fibroblast monolayers. In the presence of A or G, [125I]-LDL forms aggregates of varying size. After pre-incubation with A or G, under conditions which form highly aggregrated complexes, there is an increase in the binding of LDL to fibroblasts. Mixing with A under conditions which form smaller complexes produced no increase in binding to fibroblasts. It is suggested that interactions of this type may be involved in the pathogenesis of atherosclerosis."}
{"id": "PMID:197978", "title": "Predictable changes in low density lipoprotein composition after acute myocardial infarction.", "content": "Acute changes in low density lipoprotein cholesterol levels may be due to both a change in the number of LDL particles/ml of plasma and an alteration in the amount of cholesterol per LDL particle. Since LDL cholesterol levels are known to alter abruptly after myocardial infarction, the composition of LDL was determined in nine patients who suffered an uncomplicated transmural myocardial infarction. In six of these, LDL cholesterol levels fell whereas in three LDL cholesterol rose during the first nine days in hospital. The contents of B protein, free cholesterol, phospholipid, cholesterol ester and triglyceride in LDL were determined in the initial sample and the subsequent sample showing the greatest changes in LDL cholesterol level. The proportion of the LDL molecule contributed by B protein, free cholesterol and phospholipid did not differ significantly between the two samples. In contrast, when LDL cholesterol fell, the decrease in the proportion of cholesterol ester was disproportionately greater than in triglyceride. The opposite was observed when LDL cholesterol rose. This inverse relation between changes in LDL cholesterol ester and triglyceride could be expressed by Y = -1.02 X -0.17 (r = -0.94). These data are consistent with a pseudomicellar model of LDL in which the surface components are present in fixed amounts but the interior shell of cholesterol ester and triglyceride varies in an inverse relation depending on the absolute LDL concentration.", "contents": "Predictable changes in low density lipoprotein composition after acute myocardial infarction. Acute changes in low density lipoprotein cholesterol levels may be due to both a change in the number of LDL particles/ml of plasma and an alteration in the amount of cholesterol per LDL particle. Since LDL cholesterol levels are known to alter abruptly after myocardial infarction, the composition of LDL was determined in nine patients who suffered an uncomplicated transmural myocardial infarction. In six of these, LDL cholesterol levels fell whereas in three LDL cholesterol rose during the first nine days in hospital. The contents of B protein, free cholesterol, phospholipid, cholesterol ester and triglyceride in LDL were determined in the initial sample and the subsequent sample showing the greatest changes in LDL cholesterol level. The proportion of the LDL molecule contributed by B protein, free cholesterol and phospholipid did not differ significantly between the two samples. In contrast, when LDL cholesterol fell, the decrease in the proportion of cholesterol ester was disproportionately greater than in triglyceride. The opposite was observed when LDL cholesterol rose. This inverse relation between changes in LDL cholesterol ester and triglyceride could be expressed by Y = -1.02 X -0.17 (r = -0.94). These data are consistent with a pseudomicellar model of LDL in which the surface components are present in fixed amounts but the interior shell of cholesterol ester and triglyceride varies in an inverse relation depending on the absolute LDL concentration."}
{"id": "PMID:197981", "title": "Pharmacokinetics of pivmecillinam.", "content": "1 The plasma concentration/time curves of ampicillin and mecillinam in normal subjects were measured after oral administration of ampicillin (500 mg) and pivmecillinam (400 and 600 mg). 2 Similar plasma concentration/time curves of ampicillin and mecillinam in the starved normal subjects followed oral administration of ampicillin (500 mg) and pivmecillinam (600 mg). 3 The plasma concentration/time curve of mecillinam was measured in the same normal subjects after oral administration of pivmecillinam (400 mg) with a reproducible standardized Lundh test meal. 4 There was no statistically significant difference in the plasma concentration/time curve of mecillinam after pivmecillinam/400 mg) and the meal compared with the plasma concentration/time curve after oral pivmecillinam (400 mg) was given to the same subjects when starved. After administration of pivmecillinam (400 mg) with meal, Tasc was significantly delayed beyond the value obtained when the subjects were starved. 5 The pharmacokinetics of pivmecillinam in coeliac disease are normal. This finding contrasts with previous studies on the pharmacokinetics of another pivaloyloxymethylpenicillin ester, pivampicillin, in this condition.", "contents": "Pharmacokinetics of pivmecillinam. 1 The plasma concentration/time curves of ampicillin and mecillinam in normal subjects were measured after oral administration of ampicillin (500 mg) and pivmecillinam (400 and 600 mg). 2 Similar plasma concentration/time curves of ampicillin and mecillinam in the starved normal subjects followed oral administration of ampicillin (500 mg) and pivmecillinam (600 mg). 3 The plasma concentration/time curve of mecillinam was measured in the same normal subjects after oral administration of pivmecillinam (400 mg) with a reproducible standardized Lundh test meal. 4 There was no statistically significant difference in the plasma concentration/time curve of mecillinam after pivmecillinam/400 mg) and the meal compared with the plasma concentration/time curve after oral pivmecillinam (400 mg) was given to the same subjects when starved. After administration of pivmecillinam (400 mg) with meal, Tasc was significantly delayed beyond the value obtained when the subjects were starved. 5 The pharmacokinetics of pivmecillinam in coeliac disease are normal. This finding contrasts with previous studies on the pharmacokinetics of another pivaloyloxymethylpenicillin ester, pivampicillin, in this condition."}
{"id": "PMID:197982", "title": "A comparison of cholestyramine and nicotinic acid in the treatment of familial type II hyperlipoproteinaemia.", "content": "1 The effects of cholestyramine and nicotinic acid on plasma lipid concentration have been compared in patients with type IIa hyperlipoproteinaemia. 2 During a 3-month period, cholestyramine resulted in a mean decrease in cholesterol levels of 26%. Triglyceride levels rose in eight of the ten patients during treatment with this drug but in the majority of patients remained within the normal range. 3 During nicotinic acid therapy, cholesterol fell by a mean of 21% and triglyceride by a mean of 23%. 4 The slow release preparation of nicotinic acid used was acceptable to the majority of the patients studied and the results therefore suggest that this drug may be a useful alternative to the more widely used agent, cholestyramine.", "contents": "A comparison of cholestyramine and nicotinic acid in the treatment of familial type II hyperlipoproteinaemia. 1 The effects of cholestyramine and nicotinic acid on plasma lipid concentration have been compared in patients with type IIa hyperlipoproteinaemia. 2 During a 3-month period, cholestyramine resulted in a mean decrease in cholesterol levels of 26%. Triglyceride levels rose in eight of the ten patients during treatment with this drug but in the majority of patients remained within the normal range. 3 During nicotinic acid therapy, cholesterol fell by a mean of 21% and triglyceride by a mean of 23%. 4 The slow release preparation of nicotinic acid used was acceptable to the majority of the patients studied and the results therefore suggest that this drug may be a useful alternative to the more widely used agent, cholestyramine."}
{"id": "PMID:197989", "title": "Pulsed electron paramagnetic resonance studies of types I and II coper of Rhus vernicifera laccase and porcine ceruloplasmin.", "content": "Electron spin-echo decay envelopes for types I and II copper of Rhus vernicifera laccase and for type II copper of procine ceruloplasmin have been studied. Nuclear modulation patterns show that imidazole is a ligand for all of them. The linear electric field effect (LEFE) in EPR was studied for type I copper in a laccase preparation from which type II had been removed. The symmetry of the site is near tetrahedral and the magnitude of the LEFE is correlated with the intensity of blue color.", "contents": "Pulsed electron paramagnetic resonance studies of types I and II coper of Rhus vernicifera laccase and porcine ceruloplasmin. Electron spin-echo decay envelopes for types I and II copper of Rhus vernicifera laccase and for type II copper of procine ceruloplasmin have been studied. Nuclear modulation patterns show that imidazole is a ligand for all of them. The linear electric field effect (LEFE) in EPR was studied for type I copper in a laccase preparation from which type II had been removed. The symmetry of the site is near tetrahedral and the magnitude of the LEFE is correlated with the intensity of blue color."}
{"id": "PMID:197990", "title": "RNA phosphorylation: a polynucleotide kinase function in mouse L cell nuclei.", "content": "Analysis of [gamma-32P]ATP in vitro labeled nuclear RNA shows transfer of gamma-32P from ATP to form the 5'-terminal monophosphate for large RNA molecules. This finding is an actively transcribing nuclear system capable of guanylation and methylation reactions indicates that polynucleotide kinase activity in the eukaryotic nucleus may be functional in kinase reactions involving RNA. It further suggest a participation in the posttranscriptional modification reactions involved in RNA processing. All four nucleosides were found to act as acceptors at the 5' termini of RNA. It is also shown that both ATP and GTP can serve as donors in the nuclear polynucleotide kinase reaction.", "contents": "RNA phosphorylation: a polynucleotide kinase function in mouse L cell nuclei. Analysis of [gamma-32P]ATP in vitro labeled nuclear RNA shows transfer of gamma-32P from ATP to form the 5'-terminal monophosphate for large RNA molecules. This finding is an actively transcribing nuclear system capable of guanylation and methylation reactions indicates that polynucleotide kinase activity in the eukaryotic nucleus may be functional in kinase reactions involving RNA. It further suggest a participation in the posttranscriptional modification reactions involved in RNA processing. All four nucleosides were found to act as acceptors at the 5' termini of RNA. It is also shown that both ATP and GTP can serve as donors in the nuclear polynucleotide kinase reaction."}
{"id": "PMID:197995", "title": "The effect of phosphatidylcholine depletion on biochemical and physical properties of a Neurospora crassa membrane mutant.", "content": "By using the choline starvation process it is possible to deplete the membranes of Neurospora crassa choline auxotroph chol-1 of phosphatidylcholine, without affecting the viability of germinated spores or whole mycelium. Spin label probes were used to examine the possible dependence of the physical state of cellular lipids on the presence of phosphatidylcholine in the membranes. Increased freedom of rotational motion of lipid soluble probes was regularly detected in choline-starved mycelium. The accumulation of neutral lipids (mostly triglycerides) in bulk form was also observed during the choline starvation process. The experiments with isolated and separated lipid classes indicated that the observed increase in fluidity of lipids in choline-starved mycelium is partly due to the difference in physical properties between bulk lipids and membrane lipids. Spin label probe 2N4 (2-propyl-2,5,5-trimethyloxazolidine-N-oxyl), which can partition at the membrane-water interface, exhibited easier partitioning among membrane lipids of choline-starved mycelium.", "contents": "The effect of phosphatidylcholine depletion on biochemical and physical properties of a Neurospora crassa membrane mutant. By using the choline starvation process it is possible to deplete the membranes of Neurospora crassa choline auxotroph chol-1 of phosphatidylcholine, without affecting the viability of germinated spores or whole mycelium. Spin label probes were used to examine the possible dependence of the physical state of cellular lipids on the presence of phosphatidylcholine in the membranes. Increased freedom of rotational motion of lipid soluble probes was regularly detected in choline-starved mycelium. The accumulation of neutral lipids (mostly triglycerides) in bulk form was also observed during the choline starvation process. The experiments with isolated and separated lipid classes indicated that the observed increase in fluidity of lipids in choline-starved mycelium is partly due to the difference in physical properties between bulk lipids and membrane lipids. Spin label probe 2N4 (2-propyl-2,5,5-trimethyloxazolidine-N-oxyl), which can partition at the membrane-water interface, exhibited easier partitioning among membrane lipids of choline-starved mycelium."}
{"id": "PMID:197996", "title": "The role of enzyme I in the unmasking of an essential thiol of the membrane-bound enzyme II of the phosphoenolpyruvate-glucose phosphotransferase system of Escherichia coli.", "content": "The membrane-bound component of the phosphotransferase system of Escherichia coli, responsible for the phosphorylative uptake of methyl-alpha-D-glucoside has an essential thiol group which becomes available to inactivation by thiol reagents in the presence of the phosphate-accepting sugar or when phosphoenolpyruvate synthesis is inhibited. The form resistant to the thiol reagent requires not only the absence of sugar and an intact phosphoenolpyruvate generating system, but also an intact system generating phosphorylated Hpr which is impaired by heating of a thermosensitive enzyme I mutant.", "contents": "The role of enzyme I in the unmasking of an essential thiol of the membrane-bound enzyme II of the phosphoenolpyruvate-glucose phosphotransferase system of Escherichia coli. The membrane-bound component of the phosphotransferase system of Escherichia coli, responsible for the phosphorylative uptake of methyl-alpha-D-glucoside has an essential thiol group which becomes available to inactivation by thiol reagents in the presence of the phosphate-accepting sugar or when phosphoenolpyruvate synthesis is inhibited. The form resistant to the thiol reagent requires not only the absence of sugar and an intact phosphoenolpyruvate generating system, but also an intact system generating phosphorylated Hpr which is impaired by heating of a thermosensitive enzyme I mutant."}
{"id": "PMID:197997", "title": "Evidence for the presynaptic location of adenylate cyclase and the cyclic AMP-stimulated protein kinase which is bound to synaptic membranes.", "content": "By comparison of activities measured with either intact or ruptured synaptosomes it was found that half of the cerebral adenylate cyclase is presynaptic while all the membranes bound, cyclic AMP-stimulated protein kinase activity appears to be presynaptic with the cyclic AMP receptor facing inward.", "contents": "Evidence for the presynaptic location of adenylate cyclase and the cyclic AMP-stimulated protein kinase which is bound to synaptic membranes. By comparison of activities measured with either intact or ruptured synaptosomes it was found that half of the cerebral adenylate cyclase is presynaptic while all the membranes bound, cyclic AMP-stimulated protein kinase activity appears to be presynaptic with the cyclic AMP receptor facing inward."}
{"id": "PMID:197998", "title": "Electron spin resonance investigations of membrane proteins in erythrocytes in muscle diseases. Duchenne and myotonic muscular dystrophy and congenital myotonia.", "content": "Comparison of electron spin resonance spectra of spin labeled erythrocyte membranes from patients with the dystrophic conditions Duchenne and myotonic muscular dystrophy with those of normal controls suggests that alterations in membrane protein conformation and/or organization are present in these disease states. These protein alterations are not apparent in the non-dystrophic disease congenital myotonia. The results suggest a correlation between changes in the physical state of proteins in membranes with the presence of dystrophy. In addition, the present results from erythrocytes lend support for the concept of a generalized membrane defect in these diseases.", "contents": "Electron spin resonance investigations of membrane proteins in erythrocytes in muscle diseases. Duchenne and myotonic muscular dystrophy and congenital myotonia. Comparison of electron spin resonance spectra of spin labeled erythrocyte membranes from patients with the dystrophic conditions Duchenne and myotonic muscular dystrophy with those of normal controls suggests that alterations in membrane protein conformation and/or organization are present in these disease states. These protein alterations are not apparent in the non-dystrophic disease congenital myotonia. The results suggest a correlation between changes in the physical state of proteins in membranes with the presence of dystrophy. In addition, the present results from erythrocytes lend support for the concept of a generalized membrane defect in these diseases."}
{"id": "PMID:197999", "title": "Isolation of non-myelin plasma membranes unique to white matter.", "content": "A procedure is described for isolating two membrane fractions from rabbit spinal-cord white matter enriched with 5'-nucleotidase, a nonspecific plasma membrane marker, 2',3'-cyclic nucleotide phosphohydrolase, an oligodendroglial plasma membrane marker, and acetylcholinesterase, an axonal plasma membrane marker. While the two membrane fractions exhibited similar enrichments with respect to cyclic nucleotide phosphohydrolase, enrichments of 5'-nucleotidase and acetylcholinesterase were significantly greater in the heavier membrane fraction. Selected enzyme markers for cyto- and mitochondrial membranes were not detected. Moreover, gray matter did not yield homologous membrane fractions in the gradient when subjected to the identical procedure, indicating that the two membrane fractions were unique to white matter. While electronmicroscopic examination revealed that both membrane fractions were comtaminated with myelin, the heavier fraction was least contaminated and exhibited a fair degree of homogeneity with respect to single membrane vesicular profiles. It was concluded that both membrane fractions were enriched with oligodendroglial and axonal plasma membranes, with the heavier fraction containing significantly more axolemma.", "contents": "Isolation of non-myelin plasma membranes unique to white matter. A procedure is described for isolating two membrane fractions from rabbit spinal-cord white matter enriched with 5'-nucleotidase, a nonspecific plasma membrane marker, 2',3'-cyclic nucleotide phosphohydrolase, an oligodendroglial plasma membrane marker, and acetylcholinesterase, an axonal plasma membrane marker. While the two membrane fractions exhibited similar enrichments with respect to cyclic nucleotide phosphohydrolase, enrichments of 5'-nucleotidase and acetylcholinesterase were significantly greater in the heavier membrane fraction. Selected enzyme markers for cyto- and mitochondrial membranes were not detected. Moreover, gray matter did not yield homologous membrane fractions in the gradient when subjected to the identical procedure, indicating that the two membrane fractions were unique to white matter. While electronmicroscopic examination revealed that both membrane fractions were comtaminated with myelin, the heavier fraction was least contaminated and exhibited a fair degree of homogeneity with respect to single membrane vesicular profiles. It was concluded that both membrane fractions were enriched with oligodendroglial and axonal plasma membranes, with the heavier fraction containing significantly more axolemma."}
{"id": "PMID:198000", "title": "Miscibility properties of binary phosphatidylcholine mixtures. A calorimetric study.", "content": "From data obtained by differential scanning calorimetry phase diagrams were constructed, using a thermodynamically based fitting method. The following binary mixtures of phosphatidylcholines in water were studied: 14:0/14:0-glycerophosphocholine/16:0/16:0-glucerophosphocholine, 14:0/14:0-glycerophosphocholine/18:0/18:0-glycerophosphocholine, 12:0/12:0-glycerophosphocholine/16:0/16:0-glycerophosphocholine, 18:1t/18:1t-glycerophosphocholine/14:0/14:0-glycerophosphocholine and 18:1t/18:1t-glycerophosphocholine/16:0/16:0-glycerophosphocholine. A comparison is made of the present results with those obtained using probe techniques and the differences are discussed.", "contents": "Miscibility properties of binary phosphatidylcholine mixtures. A calorimetric study. From data obtained by differential scanning calorimetry phase diagrams were constructed, using a thermodynamically based fitting method. The following binary mixtures of phosphatidylcholines in water were studied: 14:0/14:0-glycerophosphocholine/16:0/16:0-glucerophosphocholine, 14:0/14:0-glycerophosphocholine/18:0/18:0-glycerophosphocholine, 12:0/12:0-glycerophosphocholine/16:0/16:0-glycerophosphocholine, 18:1t/18:1t-glycerophosphocholine/14:0/14:0-glycerophosphocholine and 18:1t/18:1t-glycerophosphocholine/16:0/16:0-glycerophosphocholine. A comparison is made of the present results with those obtained using probe techniques and the differences are discussed."}
{"id": "PMID:198001", "title": "The preparation and use of pyridoxal [32P]phosphate as a labeling reagent for proteins on the outer surface of membranes.", "content": "Pyridoxal [32P] phosphate was prepared using [gamma-32P] ATP, pyridoxal, and pyridoxine kinase purified from Escherichia coli B. The pyridoxal [32P] phosphate obtained had a specific activity of at least 1 Ci/mmol. This reagent was used to label intact influenza virus, red blood cells, and both normal and transformed chick embryo fibroblasts. The cell or virus to be labeled was incubated with pyridoxal [32P] phosphate. The Schiff base formed between pyridoxal [32P] phosphate and protein amino groups was reduced with NaBH4. The distribution of pyridoxal [32P] phosphate in cell membrane or virus envelope proteins was visualized by autoradiography of the proteins separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The labeling of the proteins of both influenza and chick cells appeared to be limited exclusively to those on the external surface of the virus or plasma membrane. With intact red blood cells the major portion of the probe was bound by external proteins, but a small amount of label was found associated with the internal proteins spectrin and hemoglobin.", "contents": "The preparation and use of pyridoxal [32P]phosphate as a labeling reagent for proteins on the outer surface of membranes. Pyridoxal [32P] phosphate was prepared using [gamma-32P] ATP, pyridoxal, and pyridoxine kinase purified from Escherichia coli B. The pyridoxal [32P] phosphate obtained had a specific activity of at least 1 Ci/mmol. This reagent was used to label intact influenza virus, red blood cells, and both normal and transformed chick embryo fibroblasts. The cell or virus to be labeled was incubated with pyridoxal [32P] phosphate. The Schiff base formed between pyridoxal [32P] phosphate and protein amino groups was reduced with NaBH4. The distribution of pyridoxal [32P] phosphate in cell membrane or virus envelope proteins was visualized by autoradiography of the proteins separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The labeling of the proteins of both influenza and chick cells appeared to be limited exclusively to those on the external surface of the virus or plasma membrane. With intact red blood cells the major portion of the probe was bound by external proteins, but a small amount of label was found associated with the internal proteins spectrin and hemoglobin."}
{"id": "PMID:198004", "title": "The separation of human serum high density lipoproteins by hydroxy apatite column chromatography. Evidence for the presence of discrete subfractions.", "content": "Human serum high density lipoprotein subfractions 2 and 3, isolated by preparative ultracentrifugation after blocking the enzyme phosphatidylcholine: cholesterol acyl transferase, have been subfractionated further by hydroxyapatite column chromatography. From subfraction 2 we reproducibly obtained 5 and from subfraction 3, 6 fractions differing in chemical composition and apolipoprotein content. The fractions eluting at low salt concentrations were composed primarily of apolipoprotein-A polypeptides while those eluting at high salt concentrations consisted primarily of apolipoprotein-C. From all the 11 subfractions only one contained the \"arginine-rich\" polypeptide. The apolipoprotein-C-containing fractions were richer in triacylglycerol, phospholipids and free cholesterol as compared to the apolipoprotein-A-containing ones. Although small differences of their partial specific volumes existed, the obtained values indicate that all subfractions belonged to the parent density class. The implications of these results to the current view of lipoprotein metabolism are discussed.", "contents": "The separation of human serum high density lipoproteins by hydroxy apatite column chromatography. Evidence for the presence of discrete subfractions. Human serum high density lipoprotein subfractions 2 and 3, isolated by preparative ultracentrifugation after blocking the enzyme phosphatidylcholine: cholesterol acyl transferase, have been subfractionated further by hydroxyapatite column chromatography. From subfraction 2 we reproducibly obtained 5 and from subfraction 3, 6 fractions differing in chemical composition and apolipoprotein content. The fractions eluting at low salt concentrations were composed primarily of apolipoprotein-A polypeptides while those eluting at high salt concentrations consisted primarily of apolipoprotein-C. From all the 11 subfractions only one contained the \"arginine-rich\" polypeptide. The apolipoprotein-C-containing fractions were richer in triacylglycerol, phospholipids and free cholesterol as compared to the apolipoprotein-A-containing ones. Although small differences of their partial specific volumes existed, the obtained values indicate that all subfractions belonged to the parent density class. The implications of these results to the current view of lipoprotein metabolism are discussed."}
{"id": "PMID:198005", "title": "Evidence for the glycoprotein nature of kidney renin.", "content": "The glycoprotein nature of renin isolated from either rabbit or human kidney has been demonstrated by affinity chromatography on concanavalin A-Sepharose. The bulk of rabbit renin activity bound to concanavalin A is released by 20 to 50 mM alpha-methyl-D-mannoside. Adsorption of renin is prevented by periodate oxidation prior to chromatography. Mild acid treatment (pH 2.5) prior to chromatography does not alter the concanavalin A binding profile although the pI values of native rabbit renin (5.1-5.6) are shifted into a broader distribution (4.7-6.4). The molecular weight values of rabbit renin obtained by gel filtration and those from zone centrifugation are identical (37000 +/- 1000), consistent with a low percent of carbohydrate in the glycoprotein. A hydrophobic contribution to the binding of renin by concanavalin A is evident since, in the presence of mM Ca2+ and Mn2+, higher concentrations of alpha-methyl-D-mannoside are required to affect the same release of renin at 23 degrees C compared to that at 4 degrees C. Furthermore, 25% ethylene glycol releases renin in the absence of alpha-methyl-D-mannoside. It is concluded that renin contains a small number of carbohydrate residues in relatively close proximity to a hydrophobic surface which enhances the interaction with concanavalin A.", "contents": "Evidence for the glycoprotein nature of kidney renin. The glycoprotein nature of renin isolated from either rabbit or human kidney has been demonstrated by affinity chromatography on concanavalin A-Sepharose. The bulk of rabbit renin activity bound to concanavalin A is released by 20 to 50 mM alpha-methyl-D-mannoside. Adsorption of renin is prevented by periodate oxidation prior to chromatography. Mild acid treatment (pH 2.5) prior to chromatography does not alter the concanavalin A binding profile although the pI values of native rabbit renin (5.1-5.6) are shifted into a broader distribution (4.7-6.4). The molecular weight values of rabbit renin obtained by gel filtration and those from zone centrifugation are identical (37000 +/- 1000), consistent with a low percent of carbohydrate in the glycoprotein. A hydrophobic contribution to the binding of renin by concanavalin A is evident since, in the presence of mM Ca2+ and Mn2+, higher concentrations of alpha-methyl-D-mannoside are required to affect the same release of renin at 23 degrees C compared to that at 4 degrees C. Furthermore, 25% ethylene glycol releases renin in the absence of alpha-methyl-D-mannoside. It is concluded that renin contains a small number of carbohydrate residues in relatively close proximity to a hydrophobic surface which enhances the interaction with concanavalin A."}
{"id": "PMID:198006", "title": "Determination of the exchange integral in binuclear iron-sulfur clusters in proteins of varying complexity.", "content": "The coupling constants J between the iron atoms in ferredoxin type iron-sulfur proteins containing binuclear clusters were evaluated by two parallel methods. The temperature dependence of the EPR linewidths and integrated abosrption intensities are both related to the energy of the first excited state. The values of J obtained were: center S-1 in succinate dehydrogenase, 90 cm-1; Rieske's iron-sulfur center, 65 cm-1; adrenodoxin, 270 cm-1. The behavior of iron-sulfur center N-1a in NADH:UQ reductase was also examined; its similarity to that of center S-1 indicates that center N-1a is also a binuclear iron-sulfur center, with J = 90 cm-1. Greater rhombic distortion present in the EPR spectrum of a binuclear cluster was associated with smaller values of J.", "contents": "Determination of the exchange integral in binuclear iron-sulfur clusters in proteins of varying complexity. The coupling constants J between the iron atoms in ferredoxin type iron-sulfur proteins containing binuclear clusters were evaluated by two parallel methods. The temperature dependence of the EPR linewidths and integrated abosrption intensities are both related to the energy of the first excited state. The values of J obtained were: center S-1 in succinate dehydrogenase, 90 cm-1; Rieske's iron-sulfur center, 65 cm-1; adrenodoxin, 270 cm-1. The behavior of iron-sulfur center N-1a in NADH:UQ reductase was also examined; its similarity to that of center S-1 indicates that center N-1a is also a binuclear iron-sulfur center, with J = 90 cm-1. Greater rhombic distortion present in the EPR spectrum of a binuclear cluster was associated with smaller values of J."}
{"id": "PMID:198008", "title": "Structural changes accompanying the removal of pyridoxal 5'-phosphate from phosphorylase b.", "content": "The changes in physical properties accompanying the removal of pyridoxal 5'-phosphate from glycogen phosphorylase b have been examined. The apoenzyme retains a high degree of structural rigidity, as determined from the time decay of anisotropy. The bulk of the secondary structure remains intact, although a significant change in circular dichroism indicates some degree of alteration. The mobility of a sulfhydryl-linked spin label increases. The restoration of pyridoxal 5'-phosphate reverses this effect, with indication of interaction between subunits. One or more new binding sites for 1-anilinonaphthalene-8-sulfonate appear for the apoenzyme. The kinetics of the recombination of pyridoxal 5'-phosphate with the apoenzyme, as monitored by difference spectra, indicate a high activation energy for the process. The apoenzyme is a reversibly associating system at 20-30 degrees C, pH 7.0.", "contents": "Structural changes accompanying the removal of pyridoxal 5'-phosphate from phosphorylase b. The changes in physical properties accompanying the removal of pyridoxal 5'-phosphate from glycogen phosphorylase b have been examined. The apoenzyme retains a high degree of structural rigidity, as determined from the time decay of anisotropy. The bulk of the secondary structure remains intact, although a significant change in circular dichroism indicates some degree of alteration. The mobility of a sulfhydryl-linked spin label increases. The restoration of pyridoxal 5'-phosphate reverses this effect, with indication of interaction between subunits. One or more new binding sites for 1-anilinonaphthalene-8-sulfonate appear for the apoenzyme. The kinetics of the recombination of pyridoxal 5'-phosphate with the apoenzyme, as monitored by difference spectra, indicate a high activation energy for the process. The apoenzyme is a reversibly associating system at 20-30 degrees C, pH 7.0."}
{"id": "PMID:198010", "title": "The cardiac sarcoplasmic reticulum-glycogenolytic complex. A possible effector site for cyclic AMP.", "content": "Cardiac sarcoplasmic reticulum-glycogenolytic complex, isolated as a single peak on sucrose density gradient, may function as a \"compartmented\" effector site for cyclic AMP resulting in modulation of both glycogenolysis and calcium transport. The conversion of phosphorylase b to a is stimulated by ATP and inhibited by protein kinase inhibitor. Cyclic AMP alone stimulated neither phosphorylase b to a conversion nor calcium uptake. An inhibitor of adenylate cyclase depressed both calcium uptake and phosphorylase activation and both functions were subsequently stimulated by micromolar concentrations of cyclic AMP. Endogenous phosphorylation of sarcoplasmic reticulum was also inhibited by adenylate cyclase inhibitor and the inhibition was reversed by cyclic AMP. These results suggest that the sarcoplasmic reticulum of cardiac muscle is an internal effector site for cyclic AMP which may regulate both calcium and metabolism. It appears that cyclic AMP formation in vitro is not the rate-controlling step in the activation sequence.", "contents": "The cardiac sarcoplasmic reticulum-glycogenolytic complex. A possible effector site for cyclic AMP. Cardiac sarcoplasmic reticulum-glycogenolytic complex, isolated as a single peak on sucrose density gradient, may function as a \"compartmented\" effector site for cyclic AMP resulting in modulation of both glycogenolysis and calcium transport. The conversion of phosphorylase b to a is stimulated by ATP and inhibited by protein kinase inhibitor. Cyclic AMP alone stimulated neither phosphorylase b to a conversion nor calcium uptake. An inhibitor of adenylate cyclase depressed both calcium uptake and phosphorylase activation and both functions were subsequently stimulated by micromolar concentrations of cyclic AMP. Endogenous phosphorylation of sarcoplasmic reticulum was also inhibited by adenylate cyclase inhibitor and the inhibition was reversed by cyclic AMP. These results suggest that the sarcoplasmic reticulum of cardiac muscle is an internal effector site for cyclic AMP which may regulate both calcium and metabolism. It appears that cyclic AMP formation in vitro is not the rate-controlling step in the activation sequence."}
{"id": "PMID:198014", "title": "[Interaction of cytochrome c with bilayer membranes].", "content": "Cytochrome c when adsorbed on bilayer phospholipid membrane (BLM) induced an adsorption potential of the order of 50 mv which relaxes gradually. The value and the sign of the adsorption potential depend upon the initial polarisation of the membrane. On the positively charged surface of the membrane (polarisation above 120 mv) the orientation of adsorbing molecules of the protein inverts. Ferri- and ferrocytochrome c have different affinity to phospholipids of BLM. The reduction of protein electrostatically bound to lipid bilayer causes its partial desorption when oxidation results additional adsorption of cytochrome c. Protein does not penetrate through the membrane. Electric conductivity and capacity of BLM are slightly influenced by cytochrome c adsorption. The capacity of BLM formed from an isooctane soluble complex of cytochrome c with phospholipid is less than the capacity of pure lipid bilayers.", "contents": "[Interaction of cytochrome c with bilayer membranes]. Cytochrome c when adsorbed on bilayer phospholipid membrane (BLM) induced an adsorption potential of the order of 50 mv which relaxes gradually. The value and the sign of the adsorption potential depend upon the initial polarisation of the membrane. On the positively charged surface of the membrane (polarisation above 120 mv) the orientation of adsorbing molecules of the protein inverts. Ferri- and ferrocytochrome c have different affinity to phospholipids of BLM. The reduction of protein electrostatically bound to lipid bilayer causes its partial desorption when oxidation results additional adsorption of cytochrome c. Protein does not penetrate through the membrane. Electric conductivity and capacity of BLM are slightly influenced by cytochrome c adsorption. The capacity of BLM formed from an isooctane soluble complex of cytochrome c with phospholipid is less than the capacity of pure lipid bilayers."}
{"id": "PMID:198015", "title": "[Interrelationship between structural and functional modifications in the membranes of the sarcoplasmic reticulum following lipid peroxidation].", "content": "Structural and functional modifications of sarcoplasmic reticulum membranes from skeletal muscles by molecular oxygen was studied. Lipid peroxidation (accumulation of 5-10 nmoles hydroperoxides/mg lipids) results in membrane permeability increase for Ca2+-ions whereas the activity of Ca2+-dependant ATPase preserved unchanged. In the temperature range 5-30 degrees C decrease of solubilization parameter alpha (for nitroxide radical 2,2,6,6-tetramethylpiperidin-1-oxyl) was registered while alpha reached the control values at temperatures higher than 30 degrees C. Further increase in lipoperoxide content (more than 20 nmoles/mg lipids) lead to inhibition of Ca2+dependant ATPase. In this case alpha was lower than in intack membranes in the whole temperature interval investigated. The loss of Ca2+-accumulating capacity is explained on the basis of peroxide clusters formation in lipid bilayer regions of sarcoplasmic membrane. One of the mechanisms of Ca2+-dependant ATPase inhibition after lipid peroxidation is the deficiency of polyunsaturated fatty acyls in microenvironment of the enzyme.", "contents": "[Interrelationship between structural and functional modifications in the membranes of the sarcoplasmic reticulum following lipid peroxidation]. Structural and functional modifications of sarcoplasmic reticulum membranes from skeletal muscles by molecular oxygen was studied. Lipid peroxidation (accumulation of 5-10 nmoles hydroperoxides/mg lipids) results in membrane permeability increase for Ca2+-ions whereas the activity of Ca2+-dependant ATPase preserved unchanged. In the temperature range 5-30 degrees C decrease of solubilization parameter alpha (for nitroxide radical 2,2,6,6-tetramethylpiperidin-1-oxyl) was registered while alpha reached the control values at temperatures higher than 30 degrees C. Further increase in lipoperoxide content (more than 20 nmoles/mg lipids) lead to inhibition of Ca2+dependant ATPase. In this case alpha was lower than in intack membranes in the whole temperature interval investigated. The loss of Ca2+-accumulating capacity is explained on the basis of peroxide clusters formation in lipid bilayer regions of sarcoplasmic membrane. One of the mechanisms of Ca2+-dependant ATPase inhibition after lipid peroxidation is the deficiency of polyunsaturated fatty acyls in microenvironment of the enzyme."}
{"id": "PMID:198016", "title": "[Factors influencing formation of dinitrosyl complexes of non-heme iron in vitro preparations of mouse liver and yeasts].", "content": "Total content of Fenh and its amounts incorporated into paramagnetic dinitrozyl complexes of Fenh (complexes 2.03) which are formed in vitro in homogenates of mouse liver and yeast preparations treated with nitrogen oxide was determined by means of chemical and ESR methods. Formation of the complexes 2.03 in the liver homogenate is limited by the content of easily dyalized weakly bound Fenh, in yeasts--by the content of pair RS-groups. It is suggested that in the liver preparation Fenh incorporated into the complexes 2.03 is determined by the interaction of reduction cytoplasm agents with ferritin. A change in the content of Fenh may affect the appearance and disappearance of the complexes 2.03 in animal tissues in vivo.", "contents": "[Factors influencing formation of dinitrosyl complexes of non-heme iron in vitro preparations of mouse liver and yeasts]. Total content of Fenh and its amounts incorporated into paramagnetic dinitrozyl complexes of Fenh (complexes 2.03) which are formed in vitro in homogenates of mouse liver and yeast preparations treated with nitrogen oxide was determined by means of chemical and ESR methods. Formation of the complexes 2.03 in the liver homogenate is limited by the content of easily dyalized weakly bound Fenh, in yeasts--by the content of pair RS-groups. It is suggested that in the liver preparation Fenh incorporated into the complexes 2.03 is determined by the interaction of reduction cytoplasm agents with ferritin. A change in the content of Fenh may affect the appearance and disappearance of the complexes 2.03 in animal tissues in vivo."}
{"id": "PMID:198017", "title": "[ESR study of the state of manganganese in chloroplasts].", "content": "In chloroplasts isolated in tris-HCl buffer in the presence of 0.1 M NaCl or in the absence of salts an asymmetric ESR spectrum of Mn2+ was observed which differs in shape from the ESR spectrum of Mn2+ aquanions usually observed in chloroplasts treated with ultrasonics, reducer, 0.8 M tis-HCl buffer, pH 8. The transition from asymmmetric spectrum to the symetric one takes place in the presence of reducers and in some cases is induced with light. Causes of asymmetry of the ESR spectrum of Mn2+ in chloroplasts are discussed.", "contents": "[ESR study of the state of manganganese in chloroplasts]. In chloroplasts isolated in tris-HCl buffer in the presence of 0.1 M NaCl or in the absence of salts an asymmetric ESR spectrum of Mn2+ was observed which differs in shape from the ESR spectrum of Mn2+ aquanions usually observed in chloroplasts treated with ultrasonics, reducer, 0.8 M tis-HCl buffer, pH 8. The transition from asymmmetric spectrum to the symetric one takes place in the presence of reducers and in some cases is induced with light. Causes of asymmetry of the ESR spectrum of Mn2+ in chloroplasts are discussed."}
{"id": "PMID:198018", "title": "[Mechanism of oxidative phosphorylation. III. Relationship between the composition of the mitochondrial incubation medium and functional parameters].", "content": "Functional properties of rat brain mitochondria were different in Krebs-Ringer solution as compared to these in the media with mannit. Mitochondria in the presence of cytochrme c increased endogenous respiration essentially after the introduction of mannit into the polarographic cell. It is concluded that mannit metabolised by mitochondria as other non-cell compounds, must not be in the media of incubation of mitochondria, while studying the oxidative phosphorylation mechanism.", "contents": "[Mechanism of oxidative phosphorylation. III. Relationship between the composition of the mitochondrial incubation medium and functional parameters]. Functional properties of rat brain mitochondria were different in Krebs-Ringer solution as compared to these in the media with mannit. Mitochondria in the presence of cytochrme c increased endogenous respiration essentially after the introduction of mannit into the polarographic cell. It is concluded that mannit metabolised by mitochondria as other non-cell compounds, must not be in the media of incubation of mitochondria, while studying the oxidative phosphorylation mechanism."}
{"id": "PMID:198019", "title": "[Influence of phospholipids of different natures on the structure of ferricytochrome c].", "content": "Influence of the two types of lipid molecules (neutral and acidic phospholipids) on the structure of ferricytochrome c in lipid-protein complexes was studied with the use of circular dichroism and absorption spectroscopy methods. It was found that interaction of ferricytochrome c with acidic phospholipids (cardiolipin and phosphatidylinositols) brings about some changes in the protein conformation, while interaction with neutral phospholipid (phosphatidylcholine plus 10% lauric acid) does not. Some difference in the mode of interaction of different acidic phospholipids with ferricytochrome c was also observed. As evidenced by visual light absorption spectra, cardiolipin induced the disruption of hem--methionine 80 bond in the protein molecule, while phosphatidylinositols do not cause such an effect.", "contents": "[Influence of phospholipids of different natures on the structure of ferricytochrome c]. Influence of the two types of lipid molecules (neutral and acidic phospholipids) on the structure of ferricytochrome c in lipid-protein complexes was studied with the use of circular dichroism and absorption spectroscopy methods. It was found that interaction of ferricytochrome c with acidic phospholipids (cardiolipin and phosphatidylinositols) brings about some changes in the protein conformation, while interaction with neutral phospholipid (phosphatidylcholine plus 10% lauric acid) does not. Some difference in the mode of interaction of different acidic phospholipids with ferricytochrome c was also observed. As evidenced by visual light absorption spectra, cardiolipin induced the disruption of hem--methionine 80 bond in the protein molecule, while phosphatidylinositols do not cause such an effect."}
{"id": "PMID:198024", "title": "[Oxidation and phosphorylation in rat liver nuclei and nuclear membranes in postnatal development and regeneration after partial hepatectomy].", "content": "Specific oxygen consumption by isolated nuclei of liver cells of newborn rats is higher and phosphorylation is lower as compared to adult animals. This is correlated with a higher free cytochrome oxidase activity as determined in the absence of detergents or tetramethyl-p-phenylenediamine. Correspondingly, oxygen consumption by isolated nuclear membranes of rat liver 44 hrs after partial hepatectomy is also increased and the P/O ratio is decreased 2.2-fold as compared to the controls.", "contents": "[Oxidation and phosphorylation in rat liver nuclei and nuclear membranes in postnatal development and regeneration after partial hepatectomy]. Specific oxygen consumption by isolated nuclei of liver cells of newborn rats is higher and phosphorylation is lower as compared to adult animals. This is correlated with a higher free cytochrome oxidase activity as determined in the absence of detergents or tetramethyl-p-phenylenediamine. Correspondingly, oxygen consumption by isolated nuclear membranes of rat liver 44 hrs after partial hepatectomy is also increased and the P/O ratio is decreased 2.2-fold as compared to the controls."}
{"id": "PMID:198025", "title": "[Effect on some pyridine derivatives on the activity of heart NAD glycohydrolase].", "content": "Effect of some 3- and 4-substituted pyridines on enzymatic hydrolysis of NAD by rabbit heart muscle NAD-glycohydrolase has been studied. It is shown that some 4-substituted derivatives in contrast with 3-substituted ones produce an inhibitory effect on the enzyme activity. A new efficient inhibitor of rabbit heart muscle NAD-glycohydrolase (I50 = 10(-3) M)--N1-(2-lactyl)-N2-(isonicotinoy)hydrazine, inducing uncompetitive inhibition of hydrolysis of NAD is found. The mechanism of the inhibitory effect of N1-(2-lactyl)-N2-(isonicotinoyl)hydrazine was investigated and the rate equation for enzymatic hydrolysis of NAD in the presence of inhibitor is calculated. It is suggested, that the inhibitory effect of N1-(2-lactyl)-N2-(isonicotinoyl)hydrazine is due to the formation of triple inactive complex inhibitor-enzyme-adenosinediphosphateribose.", "contents": "[Effect on some pyridine derivatives on the activity of heart NAD glycohydrolase]. Effect of some 3- and 4-substituted pyridines on enzymatic hydrolysis of NAD by rabbit heart muscle NAD-glycohydrolase has been studied. It is shown that some 4-substituted derivatives in contrast with 3-substituted ones produce an inhibitory effect on the enzyme activity. A new efficient inhibitor of rabbit heart muscle NAD-glycohydrolase (I50 = 10(-3) M)--N1-(2-lactyl)-N2-(isonicotinoy)hydrazine, inducing uncompetitive inhibition of hydrolysis of NAD is found. The mechanism of the inhibitory effect of N1-(2-lactyl)-N2-(isonicotinoyl)hydrazine was investigated and the rate equation for enzymatic hydrolysis of NAD in the presence of inhibitor is calculated. It is suggested, that the inhibitory effect of N1-(2-lactyl)-N2-(isonicotinoyl)hydrazine is due to the formation of triple inactive complex inhibitor-enzyme-adenosinediphosphateribose."}
{"id": "PMID:198026", "title": "[Enzymes of anabolic and catabolic nucleic acid pathways in human hepatomas, in liver of healthy persons, and in liver of patients with cancer of gastrointestinal tract].", "content": "The activities of enzymes catalyzing the formation of nucleic acid precursors, nucleoside kinases, as well as of those involved in the degradation of nucleic acids, were studied in nuclei of the liver of healthy persons, human hepatomas and the liver of patients with cancer of gastrointestinal tract. The activities of thymydine kinase and uridine kinase in the human hepatoma nuclear sap were found to increase 40- to 50-fold and 120- to 150-fold, respectively, as compared to those in normal human liver. The activities of DNase and RNase in the fraction of chromatin protein of human hepatomas, on the contrary, decreased almost to zero. As to the liver of patients with cancer of gastrointestinal tract, drastic alterations in the activities of nucleoside kinases and nucleases in the direction characteristic of tumors themselves were observed. This phenomenon is regarded as a manifestation of the systemic effects of the tumor on the host.", "contents": "[Enzymes of anabolic and catabolic nucleic acid pathways in human hepatomas, in liver of healthy persons, and in liver of patients with cancer of gastrointestinal tract]. The activities of enzymes catalyzing the formation of nucleic acid precursors, nucleoside kinases, as well as of those involved in the degradation of nucleic acids, were studied in nuclei of the liver of healthy persons, human hepatomas and the liver of patients with cancer of gastrointestinal tract. The activities of thymydine kinase and uridine kinase in the human hepatoma nuclear sap were found to increase 40- to 50-fold and 120- to 150-fold, respectively, as compared to those in normal human liver. The activities of DNase and RNase in the fraction of chromatin protein of human hepatomas, on the contrary, decreased almost to zero. As to the liver of patients with cancer of gastrointestinal tract, drastic alterations in the activities of nucleoside kinases and nucleases in the direction characteristic of tumors themselves were observed. This phenomenon is regarded as a manifestation of the systemic effects of the tumor on the host."}
{"id": "PMID:198022", "title": "[Interaction of ubisemiquinone with the high-potential iron-sulfur center of submitochondrial particle succinate dehydrogenase. EPR study at 240 and 12 degrees K].", "content": "The ESR spectra of beef heart submitochondrial particles were measured in the same samples at 240 degrees and 12 degrees K. There is close similarity between the inhibitory action of alpha-thenoyltrifluoroacetone, ethanol and ferricyanide on the non-saturating free radical signal SQ-2 observed at 240 degree K and peak at g=1.99 (and 2.04) which is visible only at very low temperatures. This result strongly supports our previous proposal that both ESR signals are manifestations of the ubisemiquinone complex with the High-Potential Iron-Sulfur protein of succinate dehydrogenase.", "contents": "[Interaction of ubisemiquinone with the high-potential iron-sulfur center of submitochondrial particle succinate dehydrogenase. EPR study at 240 and 12 degrees K]. The ESR spectra of beef heart submitochondrial particles were measured in the same samples at 240 degrees and 12 degrees K. There is close similarity between the inhibitory action of alpha-thenoyltrifluoroacetone, ethanol and ferricyanide on the non-saturating free radical signal SQ-2 observed at 240 degree K and peak at g=1.99 (and 2.04) which is visible only at very low temperatures. This result strongly supports our previous proposal that both ESR signals are manifestations of the ubisemiquinone complex with the High-Potential Iron-Sulfur protein of succinate dehydrogenase."}
{"id": "PMID:198027", "title": "[Effects of polyene antibiotics and detergents on cell membranes of polyene-sensitive and polyene-resistant strains of Candida albicans].", "content": "Various detergents and EPR-probes of 4,4-dimethylspiro[5alpha-androstan-17beta-ol-3,2-(1,3-oxazolidin-3-oxyl)]2CH3OH; 2,2,6,6-tetramethylpalmitoyl-amidopiperidine-1-oxyl and 2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinoxyl were used to establish structural differences in the membrane of polyene-sensitive and polyene-resistant strains of C. albicans. It was shown that the type of protein-lipid interactions is modified by the changes in the sterol component of the polyene-resistant strain membranes. This manifests itself in a decrease in sensitivity of membrane alkaline phosphatase for levorin and the detergents, as well as in the alteration of the lipid fluidity pattern of the polyene-resistant strain membranes as compared to the membranes of original culture of C. albicans. Treatment of polyene-sensitive strain membranes with amphotericine B causes more intensive protein-lipid interactions, which is not observed in case of the polyene-resistant strain. It is assumed that C. albicans resistance to polyenes is due to the existence of strong protein-lipid interactions in the membrane coupled with ergosterol substitution by other sterol components.", "contents": "[Effects of polyene antibiotics and detergents on cell membranes of polyene-sensitive and polyene-resistant strains of Candida albicans]. Various detergents and EPR-probes of 4,4-dimethylspiro[5alpha-androstan-17beta-ol-3,2-(1,3-oxazolidin-3-oxyl)]2CH3OH; 2,2,6,6-tetramethylpalmitoyl-amidopiperidine-1-oxyl and 2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinoxyl were used to establish structural differences in the membrane of polyene-sensitive and polyene-resistant strains of C. albicans. It was shown that the type of protein-lipid interactions is modified by the changes in the sterol component of the polyene-resistant strain membranes. This manifests itself in a decrease in sensitivity of membrane alkaline phosphatase for levorin and the detergents, as well as in the alteration of the lipid fluidity pattern of the polyene-resistant strain membranes as compared to the membranes of original culture of C. albicans. Treatment of polyene-sensitive strain membranes with amphotericine B causes more intensive protein-lipid interactions, which is not observed in case of the polyene-resistant strain. It is assumed that C. albicans resistance to polyenes is due to the existence of strong protein-lipid interactions in the membrane coupled with ergosterol substitution by other sterol components."}
{"id": "PMID:198028", "title": "[Interrelationship between the generation of oxygen anion-radicals and the reduction of artificial acceptors and cytochrome P-450 by NADPH-cytochrome c reductase].", "content": "The interaction of NADPH-cytochrome c reductase with oxygen, artificial acceptors and cytochrome P-450 is investigated. It is found that generation of oxygen anion-radicals (O2-), determined from the reaction of adrenaline oxidation into adrenochrome, proceeds independently on the reactions of interaction with artificial \"anaerobic\" acceptors-cytochrome c, dichlorophenolindophenol. Propylgallate competitively inhibits the reaction of adrenaline oxidation by isolated DADPH-cytochrome c reductase and non-competitively suppress the reaction of cytochrome c reduction. In contrast to the process of electron transfer on cytochrome c, there is a direct correlation between the rate of cytochrome P-450 reduction and the rate of adrenaline oxidation in liver microsomes. Hexobarbital increases V of the adrenaline oxidation reaction and does not affect the Km value, while metirapon, a metabolic inhibitor, decreases the Vmax and does not change Km. On the basis of the data obtained it is suggested that the reactions of NADPH-cytochrome c reductase interaction with oxygen and artificial \"anaerobic\" acceptors are connected with different redox-states of flavoprotein or with different flavine coenzymes, and that the electron transport on cytochrome P-450 and directly on oxygen takes place in interrelated redox-states of flavoprotein.", "contents": "[Interrelationship between the generation of oxygen anion-radicals and the reduction of artificial acceptors and cytochrome P-450 by NADPH-cytochrome c reductase]. The interaction of NADPH-cytochrome c reductase with oxygen, artificial acceptors and cytochrome P-450 is investigated. It is found that generation of oxygen anion-radicals (O2-), determined from the reaction of adrenaline oxidation into adrenochrome, proceeds independently on the reactions of interaction with artificial \"anaerobic\" acceptors-cytochrome c, dichlorophenolindophenol. Propylgallate competitively inhibits the reaction of adrenaline oxidation by isolated DADPH-cytochrome c reductase and non-competitively suppress the reaction of cytochrome c reduction. In contrast to the process of electron transfer on cytochrome c, there is a direct correlation between the rate of cytochrome P-450 reduction and the rate of adrenaline oxidation in liver microsomes. Hexobarbital increases V of the adrenaline oxidation reaction and does not affect the Km value, while metirapon, a metabolic inhibitor, decreases the Vmax and does not change Km. On the basis of the data obtained it is suggested that the reactions of NADPH-cytochrome c reductase interaction with oxygen and artificial \"anaerobic\" acceptors are connected with different redox-states of flavoprotein or with different flavine coenzymes, and that the electron transport on cytochrome P-450 and directly on oxygen takes place in interrelated redox-states of flavoprotein."}
{"id": "PMID:198031", "title": "Regulation of cyclic nucleotide phosphodiesterase activity in rhesus fetal muscle.", "content": "In both fetal and adult rhesus muscle, low levels of guanosine 3':5'-monophosphate (cyclic GMP; 0.25--5.0 micrometer) stimulated the adenosine 3':5'-monophosphate (cyclic AMP)-phosphodiesterase (PDE) at low substrate levels; the fetal enzyme was more sensitive than the adult (supernatant and particulate fractions). At high levels of substrate cyclic AMP (25--100 micrometer), hydrolysis was not influenced by either 10 or 20 micrometer cyclic GMP but the fetal and adult series were equally inhibited by 40 micrometer cyclic GMP. In the supernatant fraction cyclic AMP inhibition of cyclic GMP hydrolysis increased with increasing cyclic AMP levels. There was no difference between fetal and adult muscle preparations in percent inhibition; however, in the adult series, the inhibition was noncompetitive whereas in the fetal series the inhibition was competitive. The Ki for cyclic AMP was 40 micrometer for fetal and 100 micrometer for adult cyclic GMP-PDE. The Vmax values for cyclic GMP-PDE and both cyclic AMP-PDE enzymes were higher in the fetal series.", "contents": "Regulation of cyclic nucleotide phosphodiesterase activity in rhesus fetal muscle. In both fetal and adult rhesus muscle, low levels of guanosine 3':5'-monophosphate (cyclic GMP; 0.25--5.0 micrometer) stimulated the adenosine 3':5'-monophosphate (cyclic AMP)-phosphodiesterase (PDE) at low substrate levels; the fetal enzyme was more sensitive than the adult (supernatant and particulate fractions). At high levels of substrate cyclic AMP (25--100 micrometer), hydrolysis was not influenced by either 10 or 20 micrometer cyclic GMP but the fetal and adult series were equally inhibited by 40 micrometer cyclic GMP. In the supernatant fraction cyclic AMP inhibition of cyclic GMP hydrolysis increased with increasing cyclic AMP levels. There was no difference between fetal and adult muscle preparations in percent inhibition; however, in the adult series, the inhibition was noncompetitive whereas in the fetal series the inhibition was competitive. The Ki for cyclic AMP was 40 micrometer for fetal and 100 micrometer for adult cyclic GMP-PDE. The Vmax values for cyclic GMP-PDE and both cyclic AMP-PDE enzymes were higher in the fetal series."}
{"id": "PMID:198035", "title": "Effect of ethanol and prednisolone on growth rate and adherence of normal and SV 40 transformed hamster fibroblasts.", "content": "Ethanol decreases the growth rate of normal cells, prednisolone increases it. These factors have no effect on the growth rate of transformed cells. Ethanol increases the detachment and mortality of transformed cells, prednisolone has an inverse effect. Both factors affect neither adherence nor mortality of normal cells.", "contents": "Effect of ethanol and prednisolone on growth rate and adherence of normal and SV 40 transformed hamster fibroblasts. Ethanol decreases the growth rate of normal cells, prednisolone increases it. These factors have no effect on the growth rate of transformed cells. Ethanol increases the detachment and mortality of transformed cells, prednisolone has an inverse effect. Both factors affect neither adherence nor mortality of normal cells."}
{"id": "PMID:198036", "title": "Electron paramagnetic resonance determination of a low-lying excited state in Chromatium vinosum high-potential iron protein.", "content": "The temperature dependence of the EPR spectrum of oxidized high-potential iron protein from Chromatium vinosum has been studied. From line width and intensity measurements it is possible to determine the position of the first excited unoccupied state, 160 +/- 10 cm-1 above the ground state orbital.", "contents": "Electron paramagnetic resonance determination of a low-lying excited state in Chromatium vinosum high-potential iron protein. The temperature dependence of the EPR spectrum of oxidized high-potential iron protein from Chromatium vinosum has been studied. From line width and intensity measurements it is possible to determine the position of the first excited unoccupied state, 160 +/- 10 cm-1 above the ground state orbital."}
{"id": "PMID:198037", "title": "ESR an optical absorption studies on the copper(II) interaction with small peptides containing aromatic amino acids.", "content": "The interaction of Cu(II) with di- and tripeptides each containing phenylalanine, tryptophan or histidine in the amino acid chain has been investigated by means of electron spin resonance (ESR) and optical absorption spectroscopy. Cu(II) complexes of dipeptides and tripeptides exhibit different magnetic and optical parameters. Dipeptide complexes have larger gparallel-values and smaller A parallel values than tripeptide complexes. When compared to dipeptide complexes, the d-d band of the central metal ion is blue shifted for tripeptide complexes. There are no significant difference in the behavior of Cu(II) peptide complexes containing phenylalanine or tryptophan. Complexes of histidine containing peptides, however, show modified spectra caused by the participation of the imidazole nitrogen in the coordination to Cu(II). The imidazole nitrogen seems to coordinate in-plane with other coordinating atoms or in an axial position depending on the kind of peptide.", "contents": "ESR an optical absorption studies on the copper(II) interaction with small peptides containing aromatic amino acids. The interaction of Cu(II) with di- and tripeptides each containing phenylalanine, tryptophan or histidine in the amino acid chain has been investigated by means of electron spin resonance (ESR) and optical absorption spectroscopy. Cu(II) complexes of dipeptides and tripeptides exhibit different magnetic and optical parameters. Dipeptide complexes have larger gparallel-values and smaller A parallel values than tripeptide complexes. When compared to dipeptide complexes, the d-d band of the central metal ion is blue shifted for tripeptide complexes. There are no significant difference in the behavior of Cu(II) peptide complexes containing phenylalanine or tryptophan. Complexes of histidine containing peptides, however, show modified spectra caused by the participation of the imidazole nitrogen in the coordination to Cu(II). The imidazole nitrogen seems to coordinate in-plane with other coordinating atoms or in an axial position depending on the kind of peptide."}
{"id": "PMID:198039", "title": "A comparison between Nitrosomas europaea and Thiobacillus novellus on the basis of their oxidation systems of inorganic compounds.", "content": "Nitrosomonas europaea and Thiobacillus novellus were compared with each other on the basis of the biochemical properties of their inorganic compound-oxidizing systems. Cytochromes c of the two organisms differ considerably from each other; N. europaea cytochrome c-552 belongs to the \"bacterial-type\"  cytochrome c, while T. nouellus cytochrome c-550 resembles eucaryolic cytochrome c. The specificity of cytochrome oxidase for cytochrome c as the electron donor is different between the two organisms; T novellus oxidase reacts rapidly with cytochromes c of the organisms which seem to be higher than the organisms whose cytochromes c react rapidly with N. europaea oxidase. On the basis of these facts, N. europaea seems to be older organism than T. novellus in terms of evolution.", "contents": "A comparison between Nitrosomas europaea and Thiobacillus novellus on the basis of their oxidation systems of inorganic compounds. Nitrosomonas europaea and Thiobacillus novellus were compared with each other on the basis of the biochemical properties of their inorganic compound-oxidizing systems. Cytochromes c of the two organisms differ considerably from each other; N. europaea cytochrome c-552 belongs to the \"bacterial-type\"  cytochrome c, while T. nouellus cytochrome c-550 resembles eucaryolic cytochrome c. The specificity of cytochrome oxidase for cytochrome c as the electron donor is different between the two organisms; T novellus oxidase reacts rapidly with cytochromes c of the organisms which seem to be higher than the organisms whose cytochromes c react rapidly with N. europaea oxidase. On the basis of these facts, N. europaea seems to be older organism than T. novellus in terms of evolution."}
{"id": "PMID:198040", "title": "[Participation of the alpha- and beta-adrenoreactive systems of the brain in the regulation of contractile thermogenesis in the cat].", "content": "The influence of intraventricular injections of alpha- and beta-adrenergic substances (mesaton, phentolamine, isadrin, and propranolol) was investigated in cats. It was found that the central alpha-adrenoreceptors were involved in the shivering activating system and beta-adrenoreceptors -- in the inhibitory one.", "contents": "[Participation of the alpha- and beta-adrenoreactive systems of the brain in the regulation of contractile thermogenesis in the cat]. The influence of intraventricular injections of alpha- and beta-adrenergic substances (mesaton, phentolamine, isadrin, and propranolol) was investigated in cats. It was found that the central alpha-adrenoreceptors were involved in the shivering activating system and beta-adrenoreceptors -- in the inhibitory one."}
{"id": "PMID:198041", "title": "[Phosphoinositide content in the erythrocyte membranes of rats with spontaneous hypertension].", "content": "The values of triphosphoinositides (TPI) and monophosphoinositides (MPI) contents per 1 mg of membrane protein in the erythrocyte hosts of spontaneously hypertensive rats (SHR) constitute 178 and 74%, respectively, of that in the erythrocyte hosts of normotensive rats (NR). The total amount of phosphoinositides in the erythrocyte hosts of NR is more than 120% of the total amount of these lipids, in the erythrocyte hosts of SHR.", "contents": "[Phosphoinositide content in the erythrocyte membranes of rats with spontaneous hypertension]. The values of triphosphoinositides (TPI) and monophosphoinositides (MPI) contents per 1 mg of membrane protein in the erythrocyte hosts of spontaneously hypertensive rats (SHR) constitute 178 and 74%, respectively, of that in the erythrocyte hosts of normotensive rats (NR). The total amount of phosphoinositides in the erythrocyte hosts of NR is more than 120% of the total amount of these lipids, in the erythrocyte hosts of SHR."}
{"id": "PMID:198043", "title": "[Action of lipases on low-density serum lipoproteins].", "content": "It was shown that the action of phospholipase A2 on low density serum lipoproteins (LDL) in the presence of serum albumin led to decrease in the floatation coefficient. Lipase hydrolyzed LDL triglycerides after pretreatment of the latter with phospholipase A2. Due to the action of lipases the LDL residue loses its solubility and the cholesterol-rich precipitate forms. The loss of solubility of lipoproteins treated with lipases and proteinases may occur in vivo, underlying athermao formation, i.e. can thus serve as one of the factors in the pathogenesis of atherosclerosis.", "contents": "[Action of lipases on low-density serum lipoproteins]. It was shown that the action of phospholipase A2 on low density serum lipoproteins (LDL) in the presence of serum albumin led to decrease in the floatation coefficient. Lipase hydrolyzed LDL triglycerides after pretreatment of the latter with phospholipase A2. Due to the action of lipases the LDL residue loses its solubility and the cholesterol-rich precipitate forms. The loss of solubility of lipoproteins treated with lipases and proteinases may occur in vivo, underlying athermao formation, i.e. can thus serve as one of the factors in the pathogenesis of atherosclerosis."}
{"id": "PMID:198044", "title": "[Study of the effect of cAMP on the mitotic regimen in the esophageal epithelium of tumor-bearing mice].", "content": "The mitotic activity and number of DNA-synthesizing cells in the epithelium of the esophagus of the tumour-bearing albino mice were studied for 24 hours after the injection of dibutyryl cyclic 3', 5'-AMP. It was shown that injection of the preparation led to the blocking of cells in the G2-phase of the mitotic cycle, and to prolongation of mitosis during the first hours of the experiment without changing the total number of cells undergoing mitosis in the course of 24 hours.", "contents": "[Study of the effect of cAMP on the mitotic regimen in the esophageal epithelium of tumor-bearing mice]. The mitotic activity and number of DNA-synthesizing cells in the epithelium of the esophagus of the tumour-bearing albino mice were studied for 24 hours after the injection of dibutyryl cyclic 3', 5'-AMP. It was shown that injection of the preparation led to the blocking of cells in the G2-phase of the mitotic cycle, and to prolongation of mitosis during the first hours of the experiment without changing the total number of cells undergoing mitosis in the course of 24 hours."}
{"id": "PMID:198047", "title": "Stimulation of the hexose monophosphate shunt independent of hydrogen peroxide and superoxide production in rabbit alveolar macrophages during phagocytosis.", "content": "Phagocytosis and oxidative metabolism of human polymorphonuclear leukocytes (PMN) and rabbit alveolar macrophages (AM) were studied. Human PMN ingested a mean of 12 polyvinyl toluene latex particles (2 micrometer in diameter) per cell. There was stimulation of O2- and H2O2 production, light emission, and activation of the hexose monophosphate shunt during phagocytosis by human PMN. Rabbit AM ingested 51 latex particles (2 micrometer in diameter) per cell. There was no stimulation of the production of O2- and H2O2 or light emission associated with phagocytosis by rabbit AM, while the hexose monophosphate shunt was activated. Similar metabolic changes were obtained in both cell types when opsonized zymosan was used as phagocytic particles. 1-14C-glucoseoxidation was stimulated by H2O2 and methylene blue in both resting human PMN and rabbit AM. It is concluded that activation of the hexose monophosphate shunt in rabbit AM during phagocytosis is independent of O2- and H2O2 production.", "contents": "Stimulation of the hexose monophosphate shunt independent of hydrogen peroxide and superoxide production in rabbit alveolar macrophages during phagocytosis. Phagocytosis and oxidative metabolism of human polymorphonuclear leukocytes (PMN) and rabbit alveolar macrophages (AM) were studied. Human PMN ingested a mean of 12 polyvinyl toluene latex particles (2 micrometer in diameter) per cell. There was stimulation of O2- and H2O2 production, light emission, and activation of the hexose monophosphate shunt during phagocytosis by human PMN. Rabbit AM ingested 51 latex particles (2 micrometer in diameter) per cell. There was no stimulation of the production of O2- and H2O2 or light emission associated with phagocytosis by rabbit AM, while the hexose monophosphate shunt was activated. Similar metabolic changes were obtained in both cell types when opsonized zymosan was used as phagocytic particles. 1-14C-glucoseoxidation was stimulated by H2O2 and methylene blue in both resting human PMN and rabbit AM. It is concluded that activation of the hexose monophosphate shunt in rabbit AM during phagocytosis is independent of O2- and H2O2 production."}
{"id": "PMID:198051", "title": "Infectious hepatitis (hepatitis A) research in nonhuman primates.", "content": "A satisfactory animal model has been found for laboratory studies of human hepatitis A-namely, the white-moustached marmoset (Saguinus mystax). With this species it has been possible to perform serum-neutralization tests and to develop immune-adherence and complement-fixation tests demonstrating antigen and antibody to the virus. The recent work in marmosets has also led to determination of the agent's characteristics: it most closely resembles the enteroviruses of the picornavirus family. These advances open the way for development of a routine serologic test for diagnosis of the disease, of a human immune globulin for general use that would be precisely standardized for hepatitis A antibody, and, ultimately, of a vaccine. They also provide bases for epidemiologic studies that could reveal nonspecific measures for the disease's control. In addition, there is indication that marmosets could be used for safety control of the hepatitis B vaccine that has already been developed. An adequate supply of S. mystax-threatened by recent embargoes on their exportation-is essential to continuation of this work. The question of marmoset supply, both in the short term and over the long range, deserves serious review.", "contents": "Infectious hepatitis (hepatitis A) research in nonhuman primates. A satisfactory animal model has been found for laboratory studies of human hepatitis A-namely, the white-moustached marmoset (Saguinus mystax). With this species it has been possible to perform serum-neutralization tests and to develop immune-adherence and complement-fixation tests demonstrating antigen and antibody to the virus. The recent work in marmosets has also led to determination of the agent's characteristics: it most closely resembles the enteroviruses of the picornavirus family. These advances open the way for development of a routine serologic test for diagnosis of the disease, of a human immune globulin for general use that would be precisely standardized for hepatitis A antibody, and, ultimately, of a vaccine. They also provide bases for epidemiologic studies that could reveal nonspecific measures for the disease's control. In addition, there is indication that marmosets could be used for safety control of the hepatitis B vaccine that has already been developed. An adequate supply of S. mystax-threatened by recent embargoes on their exportation-is essential to continuation of this work. The question of marmoset supply, both in the short term and over the long range, deserves serious review."}
{"id": "PMID:198052", "title": "The herpesvirus group.", "content": "Several agents in the herpesvirus group are known to infect man. They cause a wide variety of conditions, ranging from coldsores to chickenpox and shingles. At the same time a number of the herpesviruses have been linked with malignant diseases in both lower animals and man.", "contents": "The herpesvirus group. Several agents in the herpesvirus group are known to infect man. They cause a wide variety of conditions, ranging from coldsores to chickenpox and shingles. At the same time a number of the herpesviruses have been linked with malignant diseases in both lower animals and man."}
{"id": "PMID:198050", "title": "[Effect of hyperoxia on triacylglycerol lipase activity of the rat lung (author's transl)].", "content": "An investigation of acid and neutral triacylglycerol lipases in rat lung tissue has been carried out. The effect of high oxygen concentration in the inspired gas mixture on the activities of the two triacylglycerol lipases has been studied. Hyperoxia had a strong inhibitory effect on both enzymes, the degree of inhibition being dependent on the duration of exposure. Dibutyryl-3',5' AMP and NaF restored completely the activities of the inhibited triacylglycerol lipases, while adrenaline and caffeine had no effect. The possible mechanisms of the effects of oxygen on lung triacylglycerol lipases are discussed.", "contents": "[Effect of hyperoxia on triacylglycerol lipase activity of the rat lung (author's transl)]. An investigation of acid and neutral triacylglycerol lipases in rat lung tissue has been carried out. The effect of high oxygen concentration in the inspired gas mixture on the activities of the two triacylglycerol lipases has been studied. Hyperoxia had a strong inhibitory effect on both enzymes, the degree of inhibition being dependent on the duration of exposure. Dibutyryl-3',5' AMP and NaF restored completely the activities of the inhibited triacylglycerol lipases, while adrenaline and caffeine had no effect. The possible mechanisms of the effects of oxygen on lung triacylglycerol lipases are discussed."}
{"id": "PMID:198053", "title": "Effect of isoprenaline and phenylephrine on the adenosine 3',5'-monophosphate content and mechanical activity of cold-stored and fresh taenia caecum from the guinea-pig.", "content": "1. Cold storage treatment of the guinea-pig taenia caecum had a greater inhibitory effect on the isoprenaline-induced relaxation than that induced by phenylephrine. Prolonged cold storage (12-14 days) almost abolished the effect of isoprenaline but only reduced the phenylephrine effect. The ED50 of cyclic adenosine 3',5'-monophosphate (cyclic AMP) that elicited muscle relaxation was not altered by the prolonged cold storage. 2. After cold storage treatment, tissue cyclic AMP content was decreased; however, isoprenaline still caused a dose-dependent increase in the cyclic AMP level. The threshold dose of isoprenaline for cyclic AMP accumulation was the same in fresh and cold-stored preparations. 3. In the fresh preparation, the onset of the isoprenaline (10(-6)M)-induced relaxation preceded the increase in tissue cyclic AMP. 4. Isoprenaline, phenylephrine, adrenaline and noradrenaline at doses (ED50) sufficient to induce muscle relaxation did not always increase the cyclic AMP level. 5. Similarly, the responses to papaverine and nitroglycerine were not accompanied by an increase in cyclic AMP. 6. The adenylate cyclase and phosphodiesterase (low and high Km) activities of taenia caecum were not attenuated by the prolonged cold storage. 7. Propranolol inhibited both the isoprenaline-induced relazation and cyclic AMP accumulation; however, the pA2 values were significantly different for the two events. 8. Based on these results, both the relaxation and cyclic AMP accumulation caused by isoprenaline are mediated by activation of beta-adrenoceptors but are independent phenomena.", "contents": "Effect of isoprenaline and phenylephrine on the adenosine 3',5'-monophosphate content and mechanical activity of cold-stored and fresh taenia caecum from the guinea-pig. 1. Cold storage treatment of the guinea-pig taenia caecum had a greater inhibitory effect on the isoprenaline-induced relaxation than that induced by phenylephrine. Prolonged cold storage (12-14 days) almost abolished the effect of isoprenaline but only reduced the phenylephrine effect. The ED50 of cyclic adenosine 3',5'-monophosphate (cyclic AMP) that elicited muscle relaxation was not altered by the prolonged cold storage. 2. After cold storage treatment, tissue cyclic AMP content was decreased; however, isoprenaline still caused a dose-dependent increase in the cyclic AMP level. The threshold dose of isoprenaline for cyclic AMP accumulation was the same in fresh and cold-stored preparations. 3. In the fresh preparation, the onset of the isoprenaline (10(-6)M)-induced relaxation preceded the increase in tissue cyclic AMP. 4. Isoprenaline, phenylephrine, adrenaline and noradrenaline at doses (ED50) sufficient to induce muscle relaxation did not always increase the cyclic AMP level. 5. Similarly, the responses to papaverine and nitroglycerine were not accompanied by an increase in cyclic AMP. 6. The adenylate cyclase and phosphodiesterase (low and high Km) activities of taenia caecum were not attenuated by the prolonged cold storage. 7. Propranolol inhibited both the isoprenaline-induced relazation and cyclic AMP accumulation; however, the pA2 values were significantly different for the two events. 8. Based on these results, both the relaxation and cyclic AMP accumulation caused by isoprenaline are mediated by activation of beta-adrenoceptors but are independent phenomena."}
{"id": "PMID:198054", "title": "The effect of angiotensin I converting enzyme inhibitor (SQ 20881) on the release of prostaglandins by rabbit kidney, in vivo.", "content": "1. Prostaglandin E- and F-like material has been estimated in renal venous blood of the left kidney of anaesthetized rabbits following renal nerve section. Prostaglandins were estimated by bioassay following solvent extraction and column chromatography. 2. Electrical stimulation of the renal nerves of the left kidney to reduce renal blood flow by approximately 15% for 15 min resulted in a significant increase in the concentration of prostaglandin E-like material in the renal venous blood. The peak values were normally seen either in the last 5 min of the stimulation period or in the first 5 min after the end of the stimulation period. The concentration of prostaglandin F-like material was not significantly altered. 3. Similar reduction of renal blood flow of the left kidney by renal artery constriction also resulted in a significant increase in the concentration of prostaglandin E- but not F-like material in renal venous blood. The timing and magnitude of the response was comparable with that observed with renal nerve stimuation. 4. The effect of an angiotensin I converting enzyme inhibitor, SQ 20881, on the response to both renal nerve stimulation and renal artery constriction has been studied. The administration of the drug did not significantly reduce the release of prostaglandins from the denervated kidneys, however, the increase in prostaglandin E-like material, in response to both stimuli, was abolished. 5. The results suggest that the increase in prostaglandin E-like material released from the kidney in response to low frequency stimulation or to modest reductions in renal blood flow is dependent on the release of renin and that the effect is mediated by the formation of angiotensin II and not angiotensin I.", "contents": "The effect of angiotensin I converting enzyme inhibitor (SQ 20881) on the release of prostaglandins by rabbit kidney, in vivo. 1. Prostaglandin E- and F-like material has been estimated in renal venous blood of the left kidney of anaesthetized rabbits following renal nerve section. Prostaglandins were estimated by bioassay following solvent extraction and column chromatography. 2. Electrical stimulation of the renal nerves of the left kidney to reduce renal blood flow by approximately 15% for 15 min resulted in a significant increase in the concentration of prostaglandin E-like material in the renal venous blood. The peak values were normally seen either in the last 5 min of the stimulation period or in the first 5 min after the end of the stimulation period. The concentration of prostaglandin F-like material was not significantly altered. 3. Similar reduction of renal blood flow of the left kidney by renal artery constriction also resulted in a significant increase in the concentration of prostaglandin E- but not F-like material in renal venous blood. The timing and magnitude of the response was comparable with that observed with renal nerve stimuation. 4. The effect of an angiotensin I converting enzyme inhibitor, SQ 20881, on the response to both renal nerve stimulation and renal artery constriction has been studied. The administration of the drug did not significantly reduce the release of prostaglandins from the denervated kidneys, however, the increase in prostaglandin E-like material, in response to both stimuli, was abolished. 5. The results suggest that the increase in prostaglandin E-like material released from the kidney in response to low frequency stimulation or to modest reductions in renal blood flow is dependent on the release of renin and that the effect is mediated by the formation of angiotensin II and not angiotensin I."}
{"id": "PMID:198055", "title": "A computer assisted comparison of 99Tcm-methylene-diphosphonate and 99Tcm-pyrophosphate bone imaging.", "content": "A total of 350 patient studies were carried out using clinical trials' batches of the Technetium (MDP) agent for bone scintigraphy (The Radiochemical Centre), and a commercially available Technetium pyrophosphate agent (CIS). The bone seeking properties of 99Tcm Sn-methylene-diphosphonate (MDP) and 99Tcm Sn-pyrophosphate (PYP) were evaluated by their comparative uptake in compact bone, cancellous bone and soft tissue using a region-of-interest technique. From these data uptake ratios were computed in order to correlate the values with (a) the amount of 99Tcm-MDP injected, (b) the time after injection and (c) the age of patients examined. All ratios derived with 99Tcm-MDP were superior to those using 99Tcm-PYP and were not dependent on the amount of 99Tcm-MDP injected. Uptake ratios determined for 99Tcm-MDP (1.5 h to 2.5 h after injection) were found to be higher than those for 99Tcm-PYP 2.5 to 3.5 h after injection. Soft tissue accumulation of 99Tcm-MDP, visible on scintiphotos, occurred only in 26% of cases but with 99Tcm-PYP, in 75% out of all cases studied. A decrease of cancellous bone/compact bone ratios with increasing age of the patients was found with both radiopharmaceuticals. This is most probably correlated with a diminished mass and/or surface of the cancellous bone in the elderly patient.", "contents": "A computer assisted comparison of 99Tcm-methylene-diphosphonate and 99Tcm-pyrophosphate bone imaging. A total of 350 patient studies were carried out using clinical trials' batches of the Technetium (MDP) agent for bone scintigraphy (The Radiochemical Centre), and a commercially available Technetium pyrophosphate agent (CIS). The bone seeking properties of 99Tcm Sn-methylene-diphosphonate (MDP) and 99Tcm Sn-pyrophosphate (PYP) were evaluated by their comparative uptake in compact bone, cancellous bone and soft tissue using a region-of-interest technique. From these data uptake ratios were computed in order to correlate the values with (a) the amount of 99Tcm-MDP injected, (b) the time after injection and (c) the age of patients examined. All ratios derived with 99Tcm-MDP were superior to those using 99Tcm-PYP and were not dependent on the amount of 99Tcm-MDP injected. Uptake ratios determined for 99Tcm-MDP (1.5 h to 2.5 h after injection) were found to be higher than those for 99Tcm-PYP 2.5 to 3.5 h after injection. Soft tissue accumulation of 99Tcm-MDP, visible on scintiphotos, occurred only in 26% of cases but with 99Tcm-PYP, in 75% out of all cases studied. A decrease of cancellous bone/compact bone ratios with increasing age of the patients was found with both radiopharmaceuticals. This is most probably correlated with a diminished mass and/or surface of the cancellous bone in the elderly patient."}
{"id": "PMID:198062", "title": "Neuronal circuitry in the basal septum and preoptic area of the rat.", "content": "Extracellular action potentials of spontaneously active units were studied in the basal septum and medial preoptic area (SPOA). Units responded in a similar way during stimulation of the amygdala, the reticular formation, the medial geniculate nucleus or the ventral hippocampus. The initial response was either short latency (6--35 msec) excitation or inhibition, the latter being predominant. A percentage of neurones (14.5%) did not respond. Only one response did not have an inhibitory component and responses have been further classified on the basis of the presence or absence of a postinhibitory excitation, and its rhythmicity. Single neurones tended to respond in a similar way to stimulation of different sites. Long inhibition (100--400 msec) is often preceded by excitation and may be a recurrent mechanism whilst short inhibition (18--55 msec) may be a 'direct' mechamism. Long inhibition  may be mediated by GABA as it is weakened by intravenous bicuculline whilst short inhibition was not affected. A small amplitude barrage of action potentials at the onset of inhibition was suggested to be generated by inhibitory interneurones within the SPOA. Rhythmic postinhibitory excitatory responses suggest transmission of activity from stimulation sites to the SPOA via the thalamus. A hypothesis for local neuronal circuitry of spontaneously active neurones in the SPOA was proposed.", "contents": "Neuronal circuitry in the basal septum and preoptic area of the rat. Extracellular action potentials of spontaneously active units were studied in the basal septum and medial preoptic area (SPOA). Units responded in a similar way during stimulation of the amygdala, the reticular formation, the medial geniculate nucleus or the ventral hippocampus. The initial response was either short latency (6--35 msec) excitation or inhibition, the latter being predominant. A percentage of neurones (14.5%) did not respond. Only one response did not have an inhibitory component and responses have been further classified on the basis of the presence or absence of a postinhibitory excitation, and its rhythmicity. Single neurones tended to respond in a similar way to stimulation of different sites. Long inhibition (100--400 msec) is often preceded by excitation and may be a recurrent mechanism whilst short inhibition (18--55 msec) may be a 'direct' mechamism. Long inhibition  may be mediated by GABA as it is weakened by intravenous bicuculline whilst short inhibition was not affected. A small amplitude barrage of action potentials at the onset of inhibition was suggested to be generated by inhibitory interneurones within the SPOA. Rhythmic postinhibitory excitatory responses suggest transmission of activity from stimulation sites to the SPOA via the thalamus. A hypothesis for local neuronal circuitry of spontaneously active neurones in the SPOA was proposed."}
{"id": "PMID:198063", "title": "Activity of neurons in the region of the substantia nigra during feeding in the monkey.", "content": "The activity of single neurons in the region of the substantia nigra of the monkey was recorded during feeding to investigate their function in ingestive behavior. It was observed that some neurons in the substantia nigra and the adjacent tegmentum altered their activity during feeding, in relation to mouth movements. The activity of these neurons was related to mouth movements in that the responses of the units were similar when the monkeys drank fluids with different tastes as long as the same movements were made, in that equally good responses could be obtained when the monkey moved his mouth to non-food objects, and in that in some units opposite responses were obtained when ipsilateral as compared with contralateral mouth movements were made. It was also shown that the responses of these units associated with mouth movements were similar when the monkeys were hungry and when they were satiated. These findings suggest that the activity of some neurons in the region of the substantia nigra is related to the execution of movements which may be involved in feeding, and that the activity of these neurons is not related to the initiation of feeding. Self-stimulation through the recording microelectrodes could be obtained just dorsal to the substantia nigra, but the neural basis of this self-stimulation is not known.", "contents": "Activity of neurons in the region of the substantia nigra during feeding in the monkey. The activity of single neurons in the region of the substantia nigra of the monkey was recorded during feeding to investigate their function in ingestive behavior. It was observed that some neurons in the substantia nigra and the adjacent tegmentum altered their activity during feeding, in relation to mouth movements. The activity of these neurons was related to mouth movements in that the responses of the units were similar when the monkeys drank fluids with different tastes as long as the same movements were made, in that equally good responses could be obtained when the monkey moved his mouth to non-food objects, and in that in some units opposite responses were obtained when ipsilateral as compared with contralateral mouth movements were made. It was also shown that the responses of these units associated with mouth movements were similar when the monkeys were hungry and when they were satiated. These findings suggest that the activity of some neurons in the region of the substantia nigra is related to the execution of movements which may be involved in feeding, and that the activity of these neurons is not related to the initiation of feeding. Self-stimulation through the recording microelectrodes could be obtained just dorsal to the substantia nigra, but the neural basis of this self-stimulation is not known."}
{"id": "PMID:198064", "title": "Role of norepinephrine in the release of prolactin induced by suckling and estrogen.", "content": "Release of prolactin from the anterior pituitary can be induced by a variety of neuronal and hormonal stimuli, including suckling and estrogen. To determine whether noradrenergic neurons in the central nervous system mediate the response to either of these stimuli, norepinephrine synthesis was inhibited by diethyldithiocarbamate (DDC; 50 mg/kg). When administered to suckled, lactating rats, DDC had no effect on suckling-induced increase in plasma prolactin. The drug also had no effect on prolactin levels in ovariectomized rats. However, when DDC was administered to ovariectomized rats treated with estrogen to increase plasma prolactin levels, there was a fall in plasma prolactin levels which correlated with a decrease in hypothalamic norepinephrine synthesis. It is proposed that estrogen increases noradrenergic neuron activity which in turn increases prolactin release from the pituitary.", "contents": "Role of norepinephrine in the release of prolactin induced by suckling and estrogen. Release of prolactin from the anterior pituitary can be induced by a variety of neuronal and hormonal stimuli, including suckling and estrogen. To determine whether noradrenergic neurons in the central nervous system mediate the response to either of these stimuli, norepinephrine synthesis was inhibited by diethyldithiocarbamate (DDC; 50 mg/kg). When administered to suckled, lactating rats, DDC had no effect on suckling-induced increase in plasma prolactin. The drug also had no effect on prolactin levels in ovariectomized rats. However, when DDC was administered to ovariectomized rats treated with estrogen to increase plasma prolactin levels, there was a fall in plasma prolactin levels which correlated with a decrease in hypothalamic norepinephrine synthesis. It is proposed that estrogen increases noradrenergic neuron activity which in turn increases prolactin release from the pituitary."}
{"id": "PMID:198065", "title": "Autoradiographic localization of opiate receptors in rat brain. III. The telencephalon.", "content": "Opiate receptor distribution, determined by the autoradiographic localization of stereospecific [3H]diprenorphine binding sites, was examined in the telencephalon. Areas showing very dense or dense localization of receptors included parts of the presubiculum and amygdala, patchy areas in the caudate-putamen and accumbens, the subfornical organ, the interstriatal nucleus of the striae terminalis and the anterior olfactory nucleus, pars externa. Lower densities were found in other parts of the hippocampal formation, the deeper part of the cerebral cortex, the entopeduncular nucleus, globus pallidus, nucleus triangularis septi and nucleus paratenialis. The significance of these findings is discussed in terms of the biochemical and physiological actions of opiates.", "contents": "Autoradiographic localization of opiate receptors in rat brain. III. The telencephalon. Opiate receptor distribution, determined by the autoradiographic localization of stereospecific [3H]diprenorphine binding sites, was examined in the telencephalon. Areas showing very dense or dense localization of receptors included parts of the presubiculum and amygdala, patchy areas in the caudate-putamen and accumbens, the subfornical organ, the interstriatal nucleus of the striae terminalis and the anterior olfactory nucleus, pars externa. Lower densities were found in other parts of the hippocampal formation, the deeper part of the cerebral cortex, the entopeduncular nucleus, globus pallidus, nucleus triangularis septi and nucleus paratenialis. The significance of these findings is discussed in terms of the biochemical and physiological actions of opiates."}
{"id": "PMID:198067", "title": "[Study of a virilizing adrenal cortical tumor. Analysis of urinary steroids by gas-liquid chromatography and mass spectrometry].", "content": "The C19 and C21 urinary steroids from a virilizing adrenal tumour with high levels of plasma 17alpha-progesterone and its urinary metabolites have been identified and quantitated by gas chromatography and mass spectrometry of sephadex fractions of the total urinary extract. Of the fifty five identified steroids thirteen were new compounds or known compounds not found before in such a case. The actiology of the apparent 21-steroid hydroxylase deficiency is discussed at the light of these analytical results and of the hormonogenesis enzymatic induction of the tumour biopsy.", "contents": "[Study of a virilizing adrenal cortical tumor. Analysis of urinary steroids by gas-liquid chromatography and mass spectrometry]. The C19 and C21 urinary steroids from a virilizing adrenal tumour with high levels of plasma 17alpha-progesterone and its urinary metabolites have been identified and quantitated by gas chromatography and mass spectrometry of sephadex fractions of the total urinary extract. Of the fifty five identified steroids thirteen were new compounds or known compounds not found before in such a case. The actiology of the apparent 21-steroid hydroxylase deficiency is discussed at the light of these analytical results and of the hormonogenesis enzymatic induction of the tumour biopsy."}
{"id": "PMID:198068", "title": "Effects of Solanum malacoxylon extract on rachitic chicks. Comparative study with vitamin D3.", "content": "A comparative study of the effects of vitamin D3 and of a partially purified extract of Solanum malacoxylon has been carried out in rachitic chicks. Vitamin D3 and Solanum malacoxylon increased intestinal calcium absorption and serum calcium levels. They normalized the bone water and ash content. Vitamin D3 produced an increase of serum phosphate while Solanum malacoxylon further decreased the already low phosphate values. Vitamin D3 significantly increased the body weight increment of rachitic chicks, but Solanum malacoxylon did not. It appears that Solanum malacoxylon duplicates certain actions of vitamin D but lacks its phosphate-regulating and growth-promoting actions.", "contents": "Effects of Solanum malacoxylon extract on rachitic chicks. Comparative study with vitamin D3. A comparative study of the effects of vitamin D3 and of a partially purified extract of Solanum malacoxylon has been carried out in rachitic chicks. Vitamin D3 and Solanum malacoxylon increased intestinal calcium absorption and serum calcium levels. They normalized the bone water and ash content. Vitamin D3 produced an increase of serum phosphate while Solanum malacoxylon further decreased the already low phosphate values. Vitamin D3 significantly increased the body weight increment of rachitic chicks, but Solanum malacoxylon did not. It appears that Solanum malacoxylon duplicates certain actions of vitamin D but lacks its phosphate-regulating and growth-promoting actions."}
{"id": "PMID:198069", "title": "Effect of neomycin and ionophore A23189 on ATP levels and turnover of polyphosphoinositides in human erythrocytes.", "content": "The relationship of polyphosphoinositide metabolism to erythrocyte ATP levels was examined. Turnover of polyphosphoinositides was not closely dependent on ATP as it is reported to be in yeast. Neomycin increased 32P incorporation into diphosphoinositide and to a lesser extent into triphosphoinositide without affecting intracellular ATP. Treatment of intact cells with ionophore A23187 resulted in a decrease of at least 80% in polyphosphoinositide levels which followed a decrease in cellular ATP and an increase in phosphatidate. The results indicate that polyphosphoinositide turnover does not regulate energy charge in the erythrocyte. However some of the events which follow treatment of erythrocytes with metabolic inhibitors or calcium and ionophore may be related to the accompanying decrease in polyphosphoinositide levels.", "contents": "Effect of neomycin and ionophore A23189 on ATP levels and turnover of polyphosphoinositides in human erythrocytes. The relationship of polyphosphoinositide metabolism to erythrocyte ATP levels was examined. Turnover of polyphosphoinositides was not closely dependent on ATP as it is reported to be in yeast. Neomycin increased 32P incorporation into diphosphoinositide and to a lesser extent into triphosphoinositide without affecting intracellular ATP. Treatment of intact cells with ionophore A23187 resulted in a decrease of at least 80% in polyphosphoinositide levels which followed a decrease in cellular ATP and an increase in phosphatidate. The results indicate that polyphosphoinositide turnover does not regulate energy charge in the erythrocyte. However some of the events which follow treatment of erythrocytes with metabolic inhibitors or calcium and ionophore may be related to the accompanying decrease in polyphosphoinositide levels."}
{"id": "PMID:198070", "title": "Fructose-1,6-diphosphatase activity in brown adipose tissue of the developing rat.", "content": "An enzyme activity capable of converting fructose-1,6-diphosphate to fructose-6-phosphate was demonstrated to present in crude tissue extracts from brown adipose tissue of the rat. Mg2+ was essential for the expression of activity. EDTA (0.5 mM) increased the activity by 30%. Fructose-1,6-diphosphate in concentrations of 1 and 10 mM inhibits activity by 30% and 60% respectively. A 65% inhibition was observed  in  the presence of 0.2 micrometer 5' AMP. The activity of the enzyme was measured in rat brown adipose tissue at different stages of development. It rises sharply between day 2 and day 6 and continues to increase reaching a maximum between 6 and 11 days. Thereafter the activity gradually declines to values observed prenatally. The normal developmental rise in activity could be prevented by chemical sympathectomy on day 2. This procedure had no effect when carried out on day 9. There was a significant increase in enzyme activity after cold adaptation. The possible physiological significance of this enzyme in brown adipose tissue is discussed.", "contents": "Fructose-1,6-diphosphatase activity in brown adipose tissue of the developing rat. An enzyme activity capable of converting fructose-1,6-diphosphate to fructose-6-phosphate was demonstrated to present in crude tissue extracts from brown adipose tissue of the rat. Mg2+ was essential for the expression of activity. EDTA (0.5 mM) increased the activity by 30%. Fructose-1,6-diphosphate in concentrations of 1 and 10 mM inhibits activity by 30% and 60% respectively. A 65% inhibition was observed  in  the presence of 0.2 micrometer 5' AMP. The activity of the enzyme was measured in rat brown adipose tissue at different stages of development. It rises sharply between day 2 and day 6 and continues to increase reaching a maximum between 6 and 11 days. Thereafter the activity gradually declines to values observed prenatally. The normal developmental rise in activity could be prevented by chemical sympathectomy on day 2. This procedure had no effect when carried out on day 9. There was a significant increase in enzyme activity after cold adaptation. The possible physiological significance of this enzyme in brown adipose tissue is discussed."}
{"id": "PMID:198071", "title": "Affinity chromatography of myosin, heavy meromyosin, and heavy meromyosin subfragment one on F-actin columns stabilized by phalloidin.", "content": "A method of affinity chromatography based on the trapping of actin filaments within agarose gel beads is described. This method can be used for the purification of myosin and its active proteolytic subfragments, as well as for studies on the interaction between actin and these proteins. Actin columns stabilized by phalloidin bind myosin, heavy meromyosin (HMM), and heavy meromyosin subfragment 1 (HMM-S1) specifically and reversibly. The effect of pyrophosphate and KCl on the dissociation of actomyosin, acto-HMM, or acto-HMM-S1 complex is reported. We also describe the single-step purification of myosin from a crude rabbit psoas muscle extract.", "contents": "Affinity chromatography of myosin, heavy meromyosin, and heavy meromyosin subfragment one on F-actin columns stabilized by phalloidin. A method of affinity chromatography based on the trapping of actin filaments within agarose gel beads is described. This method can be used for the purification of myosin and its active proteolytic subfragments, as well as for studies on the interaction between actin and these proteins. Actin columns stabilized by phalloidin bind myosin, heavy meromyosin (HMM), and heavy meromyosin subfragment 1 (HMM-S1) specifically and reversibly. The effect of pyrophosphate and KCl on the dissociation of actomyosin, acto-HMM, or acto-HMM-S1 complex is reported. We also describe the single-step purification of myosin from a crude rabbit psoas muscle extract."}
{"id": "PMID:198072", "title": "Insulin-like effects of fluoroacetate on lipolysis and lipogenesis in adipose tissue.", "content": "Hormone-stimulated lipolysis in adipose tissue was inhibited by fluoroacetate and there was a concomitant decrease in both the basal and hormone-stimulated cyclic AMP levels. Adenylate cyclase (EC 4.6.1.1) activity in membrane preparations was inhibited by fluoroacetate. There was no influence of fluoroacetate on the low Km cyclic AMP phosphodiesterase (EC 3.1.4.17) activity. The rate of glucose conversion to fatty acids was increased when adipose tissue was incubated in the presence of fluoroacetate. The outputs of pyruvate and lactate into the incubation medium were decreased at this time, suggesting decreased tissue pyruvate levels and a site of activation of lipogenesis distal to pyruvate formation. Pyruvate dehydrogenase (EC 1.2.4.1) activity was increased twofold in adipose tissue incubated in the presence of fluoroacetate. This was attributed to a fluoroacetate-induced inhibition of pyruvate dehydrogenase kinase, the enzyme responsible for inactivating the pyruvate dehydrogenase complex. Glucose transport was increased to a small but significant degree by fluoroacetate. In addition, both the tissue content of citrate and its release into the incubation medium were increased, suggesting that fluoroacetate resulted in an inhibition of aconitase (EC 4.2.1.3). The tissue ATP content was unchanged. Because the antilipolytic and lipogenic effects of fluoroacetate parallel those of insulin, they may share a common mechanism.", "contents": "Insulin-like effects of fluoroacetate on lipolysis and lipogenesis in adipose tissue. Hormone-stimulated lipolysis in adipose tissue was inhibited by fluoroacetate and there was a concomitant decrease in both the basal and hormone-stimulated cyclic AMP levels. Adenylate cyclase (EC 4.6.1.1) activity in membrane preparations was inhibited by fluoroacetate. There was no influence of fluoroacetate on the low Km cyclic AMP phosphodiesterase (EC 3.1.4.17) activity. The rate of glucose conversion to fatty acids was increased when adipose tissue was incubated in the presence of fluoroacetate. The outputs of pyruvate and lactate into the incubation medium were decreased at this time, suggesting decreased tissue pyruvate levels and a site of activation of lipogenesis distal to pyruvate formation. Pyruvate dehydrogenase (EC 1.2.4.1) activity was increased twofold in adipose tissue incubated in the presence of fluoroacetate. This was attributed to a fluoroacetate-induced inhibition of pyruvate dehydrogenase kinase, the enzyme responsible for inactivating the pyruvate dehydrogenase complex. Glucose transport was increased to a small but significant degree by fluoroacetate. In addition, both the tissue content of citrate and its release into the incubation medium were increased, suggesting that fluoroacetate resulted in an inhibition of aconitase (EC 4.2.1.3). The tissue ATP content was unchanged. Because the antilipolytic and lipogenic effects of fluoroacetate parallel those of insulin, they may share a common mechanism."}
{"id": "PMID:198073", "title": "The reactivity to N-ethyl maleimide of the subunits of cytochrome oxidase.", "content": "Beef heart cytochrome oxidase (EC 1.9.3.1) prepared in this laboratory consistently presents 10 Coomassie blue staining zones on SDS-polyacrylamide gel electrophoresis. At pH 7.0 only two of these polypeptides (III and VIa) are labelled by radioactive N-ethyl maleimide (NEM). The labelling of VIa is variable and correlates with activity of particular oxidase preparations. When cytochrome oxidase is isolated from alkylated membranes, either mitochrondria or electron transport particles, polypeptide VIa is found not to be labelled; polypeptide III is more strongly labelled than when isolated oxidase is alkylated, and label now appears in polypeptide I which is not alkylated upon treatment of isolated oxidase with NEM.", "contents": "The reactivity to N-ethyl maleimide of the subunits of cytochrome oxidase. Beef heart cytochrome oxidase (EC 1.9.3.1) prepared in this laboratory consistently presents 10 Coomassie blue staining zones on SDS-polyacrylamide gel electrophoresis. At pH 7.0 only two of these polypeptides (III and VIa) are labelled by radioactive N-ethyl maleimide (NEM). The labelling of VIa is variable and correlates with activity of particular oxidase preparations. When cytochrome oxidase is isolated from alkylated membranes, either mitochrondria or electron transport particles, polypeptide VIa is found not to be labelled; polypeptide III is more strongly labelled than when isolated oxidase is alkylated, and label now appears in polypeptide I which is not alkylated upon treatment of isolated oxidase with NEM."}
{"id": "PMID:198074", "title": "Characterization of the local and systemic virus neutralizing activity in swine vaccinated with a porcine enterovirus.", "content": "The virus neutralizing substance in the gastrointestinal tract of swine vaccinated in different ways with porcine enterovirus strain T80 was characterized by tests for enhancement and absorption of virus neutralizing activity by class specific antiporcine Ig antisera. The gastrointestinal virus neutralizing activity of piglets which were vaccinated with live virus orally resided predominantly in the IgA class, although some activity was present also in the IgM and IgG classes. The serum virus neutralizing activity of this group was present in all three classes but primarily in the IgG class. The IgA in the serum of this group was presumably of gut origin. However, in piglets vaccinated with live virus intramuscularly, with formaldehyde-inactivated virus orally or intramuscularly or with ethylenimine-inactivated virus by both oral and subcutaneous routes, both serum and gastrointestinal virus neutralizing activity were attributable predominantly to antibodies of the IgG and IgM classes. None possessed serum IgA. There was evidence also for the presence of Ig fragments in some gastrointestinal extracts.", "contents": "Characterization of the local and systemic virus neutralizing activity in swine vaccinated with a porcine enterovirus. The virus neutralizing substance in the gastrointestinal tract of swine vaccinated in different ways with porcine enterovirus strain T80 was characterized by tests for enhancement and absorption of virus neutralizing activity by class specific antiporcine Ig antisera. The gastrointestinal virus neutralizing activity of piglets which were vaccinated with live virus orally resided predominantly in the IgA class, although some activity was present also in the IgM and IgG classes. The serum virus neutralizing activity of this group was present in all three classes but primarily in the IgG class. The IgA in the serum of this group was presumably of gut origin. However, in piglets vaccinated with live virus intramuscularly, with formaldehyde-inactivated virus orally or intramuscularly or with ethylenimine-inactivated virus by both oral and subcutaneous routes, both serum and gastrointestinal virus neutralizing activity were attributable predominantly to antibodies of the IgG and IgM classes. None possessed serum IgA. There was evidence also for the presence of Ig fragments in some gastrointestinal extracts."}
{"id": "PMID:198075", "title": "The protective effect of two porcine enterovirus vaccines in swine.", "content": "Piglets vaccinated with a single oral dose of live porcine enterovirus strain T80 were protected to a highly significant degree against an oral challenge dose of 140 plaque forming units of T80 virus, in comparison with nonvaccinated controls, in terms of serum antibody response, titres and distribution of virus in the gastrointestinal tract contents and tissues and duration of virus excretion in the feces. Piglets vaccinated with multiple doses of adjuvanted, PE60-concentrated ethylenimine-inactivated virus administered both orally and subcutaneously showed only a slight degree of protection against the same challenge dose, despite the fact that they possessed high serum antibody titres at the time of challenge. Piglets vaccinated orally with live virus showed a degree of protection even against a challenge dose of 10(7.41) plaque forming units of T80 virus in terms of titres and distribution of virus in the gastrointestinal tract and duration of excretion of virus in the feces. Protection in the piglets dosed orally with live virus appeared to be attributable to the presence of relatively high levels of virus neutralizing antibody of the IgA class in the gastrointestinal tract.", "contents": "The protective effect of two porcine enterovirus vaccines in swine. Piglets vaccinated with a single oral dose of live porcine enterovirus strain T80 were protected to a highly significant degree against an oral challenge dose of 140 plaque forming units of T80 virus, in comparison with nonvaccinated controls, in terms of serum antibody response, titres and distribution of virus in the gastrointestinal tract contents and tissues and duration of virus excretion in the feces. Piglets vaccinated with multiple doses of adjuvanted, PE60-concentrated ethylenimine-inactivated virus administered both orally and subcutaneously showed only a slight degree of protection against the same challenge dose, despite the fact that they possessed high serum antibody titres at the time of challenge. Piglets vaccinated orally with live virus showed a degree of protection even against a challenge dose of 10(7.41) plaque forming units of T80 virus in terms of titres and distribution of virus in the gastrointestinal tract and duration of excretion of virus in the feces. Protection in the piglets dosed orally with live virus appeared to be attributable to the presence of relatively high levels of virus neutralizing antibody of the IgA class in the gastrointestinal tract."}
{"id": "PMID:198076", "title": "Bovine lymphosarcoma in twin calves.", "content": "Lymphosarcoma in twin female calves, apparently the first to be observed in Canada, is reported here. Peripheral blood and cultured mononuclear cells of one of the calves showed aneuploidy of the chromosomes. No hematological or serological evidence of bovine leukemia virus infection was observed in the other members of the herd. Bovine leukemia virus infection of the leukemic cells could not be detected by electron microscopy or by tissue culture procedures. There is a need to clarify the relationship of the calf form of the disease to the adult form of enzootic bovine leukosis.", "contents": "Bovine lymphosarcoma in twin calves. Lymphosarcoma in twin female calves, apparently the first to be observed in Canada, is reported here. Peripheral blood and cultured mononuclear cells of one of the calves showed aneuploidy of the chromosomes. No hematological or serological evidence of bovine leukemia virus infection was observed in the other members of the herd. Bovine leukemia virus infection of the leukemic cells could not be detected by electron microscopy or by tissue culture procedures. There is a need to clarify the relationship of the calf form of the disease to the adult form of enzootic bovine leukosis."}
{"id": "PMID:198077", "title": "Isolation of a new porcine enterovirus in the United States.", "content": "A cytopathogenic virus isolated from an Iowa farm pig with diarrhea was identified as a member of Group 5 of the porcine enteroviruses. Clinical signs observed in other pigs in the herd were diarrhea, debilitation and gauntness. Morbidity and mortality rates were approximately 50% and 3% respectively.A Group 5 porcine enterovirus had not been previously isolated in North America according to the Western Hemisphere Committee on Animal Virus Characterization.", "contents": "Isolation of a new porcine enterovirus in the United States. A cytopathogenic virus isolated from an Iowa farm pig with diarrhea was identified as a member of Group 5 of the porcine enteroviruses. Clinical signs observed in other pigs in the herd were diarrhea, debilitation and gauntness. Morbidity and mortality rates were approximately 50% and 3% respectively.A Group 5 porcine enterovirus had not been previously isolated in North America according to the Western Hemisphere Committee on Animal Virus Characterization."}
{"id": "PMID:198078", "title": "Depression of glutamate-mediated synaptic transmission by benzyl alcohol.", "content": "The data obtained from this study suggest that the nonionizable anesthetic benzyl alcohol has two prominent actions on GABA- and glutamate-mediated synaptic transmission at the lobster neuromuscular junction. They are as follows: (1) depression of the excitatory end-plate potential and the postsynaptic membrane response to applied glutamate, and (2) a hyperpolarization of the postsynaptic resting membrane potential associated with a decrease in effective membrane resistance. No change in amplitude of the inhibitory end-plate potential or inhibitory reversal potential was seen. Excitatory miniature end-plate potential frequency was also unaffected. The depression of excitatory synaptic transmission appears to be due to a decreased responsiveness of the postsynaptic receptor-ionophore complex.", "contents": "Depression of glutamate-mediated synaptic transmission by benzyl alcohol. The data obtained from this study suggest that the nonionizable anesthetic benzyl alcohol has two prominent actions on GABA- and glutamate-mediated synaptic transmission at the lobster neuromuscular junction. They are as follows: (1) depression of the excitatory end-plate potential and the postsynaptic membrane response to applied glutamate, and (2) a hyperpolarization of the postsynaptic resting membrane potential associated with a decrease in effective membrane resistance. No change in amplitude of the inhibitory end-plate potential or inhibitory reversal potential was seen. Excitatory miniature end-plate potential frequency was also unaffected. The depression of excitatory synaptic transmission appears to be due to a decreased responsiveness of the postsynaptic receptor-ionophore complex."}
{"id": "PMID:198079", "title": "Cannabinoid effects on adenylate cyclase and phosphodiesterase activities of mouse brain.", "content": "The experiments presented in this paper examine the mechanisms underlying the ability of cannabinoids to alter the in vivo levels of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in mouse brain. It was found that changes in cyclic AMP levels are a composite result of direct actions of cannabinoids on adenylate cyclase (EC 4.6.1.1) activity and indirect actions involving the potentiation or inhibition of biogenic amine induced activity of adenylate cyclase. Furthermore, the long-term intraperitoneal administration of 1-(--)-delta-tetrahydrocannabinol to mice produced a form of phosphodiesterase (EC 3.1.4.17) in the brain whose activity is not stimulated by Ca2+, although its basal specific activity is similar to that of control animals. In vitro, the presence of the cannabinoids caused no significant changes in activity of brain PDE at the concentrations tested. Some correlations are presented which imply that many of the observed behavioral and physiological actions of the cannabinoids in mammalian organisms may be mediated via cyclic AMP mechanisms.", "contents": "Cannabinoid effects on adenylate cyclase and phosphodiesterase activities of mouse brain. The experiments presented in this paper examine the mechanisms underlying the ability of cannabinoids to alter the in vivo levels of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in mouse brain. It was found that changes in cyclic AMP levels are a composite result of direct actions of cannabinoids on adenylate cyclase (EC 4.6.1.1) activity and indirect actions involving the potentiation or inhibition of biogenic amine induced activity of adenylate cyclase. Furthermore, the long-term intraperitoneal administration of 1-(--)-delta-tetrahydrocannabinol to mice produced a form of phosphodiesterase (EC 3.1.4.17) in the brain whose activity is not stimulated by Ca2+, although its basal specific activity is similar to that of control animals. In vitro, the presence of the cannabinoids caused no significant changes in activity of brain PDE at the concentrations tested. Some correlations are presented which imply that many of the observed behavioral and physiological actions of the cannabinoids in mammalian organisms may be mediated via cyclic AMP mechanisms."}
{"id": "PMID:198080", "title": "Virus detection on grapes.", "content": "Grapes inoculated with poliovirus 1 and coxsackievirus B5 were washed with water, 0.5% polyehtylene glycol, or phosphate-buffered saline with 1% serum. These washes were equally efficient at removing virus but much of the virus in the water was noninfectious until treated with 0.5% polyethylene glycol.", "contents": "Virus detection on grapes. Grapes inoculated with poliovirus 1 and coxsackievirus B5 were washed with water, 0.5% polyehtylene glycol, or phosphate-buffered saline with 1% serum. These washes were equally efficient at removing virus but much of the virus in the water was noninfectious until treated with 0.5% polyethylene glycol."}
{"id": "PMID:198082", "title": "Treatment of trophoblastic neoplasia at the Cancer Control Agency of British Columbia.", "content": "Over a period of 29 years 30 patients with gestational trophoblastic neoplasia were referred to the Cancer Control Agency of British Columbia. Five patients had benign disease and required no further treatment after having had dilatation and curettage. The remaining 25 patients were treated with methotrexate or hysterectomy, or both. Actuarial survival rates were 96.4% at 1 year and 90.6% at 5 years. There was a high correlation between malignancy and high titres of human chorionic gonadotropin (HCG). All cases of hydatidiform mole must be followed closely by means of estimations of HCG titre.", "contents": "Treatment of trophoblastic neoplasia at the Cancer Control Agency of British Columbia. Over a period of 29 years 30 patients with gestational trophoblastic neoplasia were referred to the Cancer Control Agency of British Columbia. Five patients had benign disease and required no further treatment after having had dilatation and curettage. The remaining 25 patients were treated with methotrexate or hysterectomy, or both. Actuarial survival rates were 96.4% at 1 year and 90.6% at 5 years. There was a high correlation between malignancy and high titres of human chorionic gonadotropin (HCG). All cases of hydatidiform mole must be followed closely by means of estimations of HCG titre."}
{"id": "PMID:198083", "title": "Criteria of complete remission from trophoblastic neoplasia with the use of human chorionic gonadotropin (HCG) excretion pattern as a parameter.", "content": "The excretion pattern of human chorionic gonadotropin (hCG) or luteinizing hormone (LH) was observed in the urine of 77 patients with trophoblastic neoplasia, 109 with complete remission from trophoblastic neoplasia, and 94 with no trophoblastic neoplasia, when the anti-beta-subunit hCG system radioimmunoassay (anti-beta-subunit RIA), which specifically measured hCG was used. The sensitivity of anti-beta-subunit RIA was limited to urinary hCG 16 mIL/ml from the specificity of the anti-beta-subunit serum. Luteinizing hormone in the urine of patients with complete remission and in normal menstrual, postmenopausal, and castrated women was less than 16 mIU/ml in most cases. The excretion pattern of urinary hCG in the patients undergoing treatment for trophoblastic neoplasia was more clearly comprehended with the anti-beta-subunit RIA as compared with the anti-hCH RIA. The criteria for judgment of complete remission were that the hCG value dropped to less than 16 mIU/ml and that cellular response was not observed at least in the last two courses.", "contents": "Criteria of complete remission from trophoblastic neoplasia with the use of human chorionic gonadotropin (HCG) excretion pattern as a parameter. The excretion pattern of human chorionic gonadotropin (hCG) or luteinizing hormone (LH) was observed in the urine of 77 patients with trophoblastic neoplasia, 109 with complete remission from trophoblastic neoplasia, and 94 with no trophoblastic neoplasia, when the anti-beta-subunit hCG system radioimmunoassay (anti-beta-subunit RIA), which specifically measured hCG was used. The sensitivity of anti-beta-subunit RIA was limited to urinary hCG 16 mIL/ml from the specificity of the anti-beta-subunit serum. Luteinizing hormone in the urine of patients with complete remission and in normal menstrual, postmenopausal, and castrated women was less than 16 mIU/ml in most cases. The excretion pattern of urinary hCG in the patients undergoing treatment for trophoblastic neoplasia was more clearly comprehended with the anti-beta-subunit RIA as compared with the anti-hCH RIA. The criteria for judgment of complete remission were that the hCG value dropped to less than 16 mIU/ml and that cellular response was not observed at least in the last two courses."}
{"id": "PMID:198084", "title": "Immunotherapy with autologous white cell infusions (\"lymphocytes\") in the treatment of recurrrent glioblastoma multiforme: a preliminary report.", "content": "Autologous leukocytes (10(7) to 10(9)), obtained with the Haemonetic's Leukaphoresis apparatus, were inoculated directly into recurrent glioblastoma tumors via indwelling catheters or by direct intratumoral injection through existing craniotomy openings. The rational use for autologous leukocyte (lymphocyte) infusions was based on in vitro autologous lymphocyte cytotoxicity to glioblastoma cells in the absence of serum inhibitory factors. Seven of 17 patients treated had life expectancy under 1 month; all patients had received definitive surgery, and all but two received radiation, nitrosourea chemotherapy and/or dexamethasone, and showed evidence of clinically recurrent disease. Following autologous leukocyte infusion (lymphocyte/granulocyte ratio 1:1), eight patients sustained clinical improvement and were alive up to 17 months later. No neurotoxicity ascribable to the procedure has been observed. One patient, who was comatose at the time of single leukocyte infusion, returned to full activity and lived for 17 months without an increase in tumor mass by brain scan. These results suggest that infusions of autologous leukocytes (lymphocyte-monocytes) directly into glioblastoma may be a viable additional treatment for glioblastoma and certainly warrants further evaluation.", "contents": "Immunotherapy with autologous white cell infusions (\"lymphocytes\") in the treatment of recurrrent glioblastoma multiforme: a preliminary report. Autologous leukocytes (10(7) to 10(9)), obtained with the Haemonetic's Leukaphoresis apparatus, were inoculated directly into recurrent glioblastoma tumors via indwelling catheters or by direct intratumoral injection through existing craniotomy openings. The rational use for autologous leukocyte (lymphocyte) infusions was based on in vitro autologous lymphocyte cytotoxicity to glioblastoma cells in the absence of serum inhibitory factors. Seven of 17 patients treated had life expectancy under 1 month; all patients had received definitive surgery, and all but two received radiation, nitrosourea chemotherapy and/or dexamethasone, and showed evidence of clinically recurrent disease. Following autologous leukocyte infusion (lymphocyte/granulocyte ratio 1:1), eight patients sustained clinical improvement and were alive up to 17 months later. No neurotoxicity ascribable to the procedure has been observed. One patient, who was comatose at the time of single leukocyte infusion, returned to full activity and lived for 17 months without an increase in tumor mass by brain scan. These results suggest that infusions of autologous leukocytes (lymphocyte-monocytes) directly into glioblastoma may be a viable additional treatment for glioblastoma and certainly warrants further evaluation."}
{"id": "PMID:198086", "title": "Experiment with 659 consecutive lymphograms in children.", "content": "Between 1963 and January 30, 1975, 659 children under 16 years of age were referred for bipedal lymphography at the Institut Gustave-Roussy. Approximately one-third were under 5 years of age. The vast majority had documented malignant disease. Successful bilateral lymphatic cannulation and lymph nodd opacification were accomplished in 86.7% of all children. Another 11.6% had successful unilateral lymphograms, which usually provided sufficient information to be considered as diagnostic stldies. In only 1.7% of all children was the study unsuccessful bilaterally. Lymphatic cannulation failure rates progressively decreased as the child increased in age. There were five \"allergic\" reactions (0.75%), one of which was considered life-threatening, and one instance (0.15%) of a transient neurological deficit. No permanent sequelae or deaths were attributed to the lymphogram.", "contents": "Experiment with 659 consecutive lymphograms in children. Between 1963 and January 30, 1975, 659 children under 16 years of age were referred for bipedal lymphography at the Institut Gustave-Roussy. Approximately one-third were under 5 years of age. The vast majority had documented malignant disease. Successful bilateral lymphatic cannulation and lymph nodd opacification were accomplished in 86.7% of all children. Another 11.6% had successful unilateral lymphograms, which usually provided sufficient information to be considered as diagnostic stldies. In only 1.7% of all children was the study unsuccessful bilaterally. Lymphatic cannulation failure rates progressively decreased as the child increased in age. There were five \"allergic\" reactions (0.75%), one of which was considered life-threatening, and one instance (0.15%) of a transient neurological deficit. No permanent sequelae or deaths were attributed to the lymphogram."}
{"id": "PMID:198087", "title": "Cervical carcinoma with adenoid cystic pattern: a light and electron microscopic study.", "content": "Three cases of cervical carcinoma with an adenoid cystic pattern were studied by light and electron microscopy. All were found to be compatible with the histologic picture of adenoid cystic carcinoma in other body sites. Although there was some variability in the pattern among the tumors, areas of each exhibited a cribriform appearance characterized by small cells with sparse cytoplasm arranged around cystic gland-like lumina. Only one tumor displayed cylindromatous formations similar to those described by Billroth. Two of the tumors were associated with foci of squamous cell carcinoma while the third contained areas suggestive of such a component. Electron microscopic examination showed varied morphology of the cysts, manifested by true glandlike lumina, extracellular spaces containing replicated basement membrane or enclosed stroma. In view of the observed diversity in the light and electron microscopic morphology of adenoid cystic carcinomas of the cervix, it is apparent that this tumor is not a distinct histologic entity. Accordingly, it is recommended that the terminology \"cervical carcinoma with adenoid cystic pattern\" be utilized.", "contents": "Cervical carcinoma with adenoid cystic pattern: a light and electron microscopic study. Three cases of cervical carcinoma with an adenoid cystic pattern were studied by light and electron microscopy. All were found to be compatible with the histologic picture of adenoid cystic carcinoma in other body sites. Although there was some variability in the pattern among the tumors, areas of each exhibited a cribriform appearance characterized by small cells with sparse cytoplasm arranged around cystic gland-like lumina. Only one tumor displayed cylindromatous formations similar to those described by Billroth. Two of the tumors were associated with foci of squamous cell carcinoma while the third contained areas suggestive of such a component. Electron microscopic examination showed varied morphology of the cysts, manifested by true glandlike lumina, extracellular spaces containing replicated basement membrane or enclosed stroma. In view of the observed diversity in the light and electron microscopic morphology of adenoid cystic carcinomas of the cervix, it is apparent that this tumor is not a distinct histologic entity. Accordingly, it is recommended that the terminology \"cervical carcinoma with adenoid cystic pattern\" be utilized."}
{"id": "PMID:198088", "title": "Carcinoma in situ of the breast.", "content": "A series of 87 cases of carcinoma in situ of the breast was reviewed. IN 49 CASes in which lobular carcinoma in situ was shown on biopsy, three patients were found to have invasive carcinoma in the subsequently done mastectomy. All three of these cases were in a group of 14 patients shown in have bilateral lobular carcinoma in situ on biopsy. In a group of 38 patients with intraductal carcinoma on biopsy, seven were found to have invasive carcinoma in the mastectomy that was subsequently done. Lymph node metastases were found in one patient in the lobular group and four patients in the intraductal group. Three patients in the intraductal group died of cancer. None in the lobular group has died of cancer.", "contents": "Carcinoma in situ of the breast. A series of 87 cases of carcinoma in situ of the breast was reviewed. IN 49 CASes in which lobular carcinoma in situ was shown on biopsy, three patients were found to have invasive carcinoma in the subsequently done mastectomy. All three of these cases were in a group of 14 patients shown in have bilateral lobular carcinoma in situ on biopsy. In a group of 38 patients with intraductal carcinoma on biopsy, seven were found to have invasive carcinoma in the mastectomy that was subsequently done. Lymph node metastases were found in one patient in the lobular group and four patients in the intraductal group. Three patients in the intraductal group died of cancer. None in the lobular group has died of cancer."}
{"id": "PMID:198089", "title": "Intranuclear tubular structures observed in the cells of an alveolar cell carcinoma of the lung.", "content": "Intranuclear tubular structures observed in the cells of an alveolar cell carcinoma of the lung are described. The structures were composed of membraneous tubules, measured about 60 nm in diameter, and had an electron-dense central core. These unusual structures were seen in the nuclei of neoplastic cells (Type II pneumocytes). The nature of the tubular structures remains unsolved, but morphologic characteristics and associated grnaulomatous reaction in the stroma imply the possibility of an unknown virus-like infection.", "contents": "Intranuclear tubular structures observed in the cells of an alveolar cell carcinoma of the lung. Intranuclear tubular structures observed in the cells of an alveolar cell carcinoma of the lung are described. The structures were composed of membraneous tubules, measured about 60 nm in diameter, and had an electron-dense central core. These unusual structures were seen in the nuclei of neoplastic cells (Type II pneumocytes). The nature of the tubular structures remains unsolved, but morphologic characteristics and associated grnaulomatous reaction in the stroma imply the possibility of an unknown virus-like infection."}
{"id": "PMID:198090", "title": "Basosquamous (transitional cloacogenic) carcinoma of the sigmoid colon.", "content": "A case of basosquamous or so-called transitional cloacogenic carcinoma of the sigmoid colon, which arose above the pelvic brim at the peritoneal reflection, is reported. We were not able to find a report of this histologic type of tumor arising this far from the pectinate line of the anus, which is the most common primary site of this neoplasm. Possibilities as to the histogenesis of this tumor at this site are stated. The neoplasm also produced parathyroid hormone (PTH) and also possibly adrenal corticotrophic hormone (ACTH), which had not been previously reported for this specific neoplasm.", "contents": "Basosquamous (transitional cloacogenic) carcinoma of the sigmoid colon. A case of basosquamous or so-called transitional cloacogenic carcinoma of the sigmoid colon, which arose above the pelvic brim at the peritoneal reflection, is reported. We were not able to find a report of this histologic type of tumor arising this far from the pectinate line of the anus, which is the most common primary site of this neoplasm. Possibilities as to the histogenesis of this tumor at this site are stated. The neoplasm also produced parathyroid hormone (PTH) and also possibly adrenal corticotrophic hormone (ACTH), which had not been previously reported for this specific neoplasm."}
{"id": "PMID:198091", "title": "Clinicopathologic features of encapsulated hepatocellular carcinoma: a study of 26 cases.", "content": "The clinicopathologic features of 26 cases of hepatocellular carcinoma (HCC) surrounded by a grossly distinct capsule-like fibrous tissue were studied. The frequency of this type was 10.3% among autopsy cases of HCC. The mean age of the patients was 64.1 years, which was significantly older compared with that of 143 cases of nonencapsulated HCC. Hepatitis-B surface antigen in serum was positive in 18.7% of the cases studied, the positivity rate being lower than that of HCC in general. Histologically, the tumor was relatively well differentiated and the capsule was the product of slow expanding growth. Intravenous tumor invasion was less frequent compared with other types of HCC. Clinically, celiac angiography proves to be a most useful diagnostic method; a thick capsule may be demonstrated as a thin radiolucent rim around the mass. The clinical course from the early stage is protracted and, if detected early, this type of HCC may be removed surgically.", "contents": "Clinicopathologic features of encapsulated hepatocellular carcinoma: a study of 26 cases. The clinicopathologic features of 26 cases of hepatocellular carcinoma (HCC) surrounded by a grossly distinct capsule-like fibrous tissue were studied. The frequency of this type was 10.3% among autopsy cases of HCC. The mean age of the patients was 64.1 years, which was significantly older compared with that of 143 cases of nonencapsulated HCC. Hepatitis-B surface antigen in serum was positive in 18.7% of the cases studied, the positivity rate being lower than that of HCC in general. Histologically, the tumor was relatively well differentiated and the capsule was the product of slow expanding growth. Intravenous tumor invasion was less frequent compared with other types of HCC. Clinically, celiac angiography proves to be a most useful diagnostic method; a thick capsule may be demonstrated as a thin radiolucent rim around the mass. The clinical course from the early stage is protracted and, if detected early, this type of HCC may be removed surgically."}
{"id": "PMID:198092", "title": "Adenoid cystic carcinoma of the larynx: a report of four cases and a review of the literature.", "content": "Adenoid cystic carcinoma (cylindroma) is a well-recognized tumor that is frequently encountered in the major salivary glands, the lacrimal glands and in the minor salivary glands of the oral cavity and upper respiratory tract. Only 60 cases of adenoid cystic carcinoma have been described arising in the larynx. Four new cases are reported and the literature is reviewed. In the larynx, these tumors arise almost exclusively in the subglottic and supraglottic regions--areas having large numbers of seromucinous glands of the minor salivary gland type. These malignant tumors, whether occurring in the larynx or elsewhere, tend to grow quite slowly with prolonged non-specific symptomatology and protracted clinical course. Despite their slow growth, in a majority of cases, they eventually lead to the death of the patient.", "contents": "Adenoid cystic carcinoma of the larynx: a report of four cases and a review of the literature. Adenoid cystic carcinoma (cylindroma) is a well-recognized tumor that is frequently encountered in the major salivary glands, the lacrimal glands and in the minor salivary glands of the oral cavity and upper respiratory tract. Only 60 cases of adenoid cystic carcinoma have been described arising in the larynx. Four new cases are reported and the literature is reviewed. In the larynx, these tumors arise almost exclusively in the subglottic and supraglottic regions--areas having large numbers of seromucinous glands of the minor salivary gland type. These malignant tumors, whether occurring in the larynx or elsewhere, tend to grow quite slowly with prolonged non-specific symptomatology and protracted clinical course. Despite their slow growth, in a majority of cases, they eventually lead to the death of the patient."}
{"id": "PMID:198093", "title": "Oncocytoma of the lung.", "content": "A tumor diagnosed as an oncocytoma was removed from the lower right lung of a 22-year-old patient. Specimens from the formalin fixed tumor were studied by light microscopy and by electron microscopy. Large numbers of mitochondria were observed in all the tumor cells at the ultrastructural level despite many artefacts due to fixation. The presence of two tumor cell types \"typical\" oncocytes and \"condensed\" oncocytes were demonstrated by electron microscopy. This appears to be the second pulmonary oncocytoma in which mitochondrial hyperplaxia has been demonstrated. The tumor was similar to previously reported cases of salivary gland oncocytomas.", "contents": "Oncocytoma of the lung. A tumor diagnosed as an oncocytoma was removed from the lower right lung of a 22-year-old patient. Specimens from the formalin fixed tumor were studied by light microscopy and by electron microscopy. Large numbers of mitochondria were observed in all the tumor cells at the ultrastructural level despite many artefacts due to fixation. The presence of two tumor cell types \"typical\" oncocytes and \"condensed\" oncocytes were demonstrated by electron microscopy. This appears to be the second pulmonary oncocytoma in which mitochondrial hyperplaxia has been demonstrated. The tumor was similar to previously reported cases of salivary gland oncocytomas."}
{"id": "PMID:198094", "title": "Antibody responses in normal infants and in infants receiving chemotherapy for congenital neuroblastoma.", "content": "Three infants with congenital neuroblastoma received a primary series of diptheria-pertassis-tetanus (DPT) immunizations during and after courses of chemotherapy with immunosuppressive medications. Serum IgG, IgA and IgM levels and antidiphthria and antitetanus antibody responses were measured and compared with those of normal infants of similar age. Protective levels of antibody were achieved by the study patients as well as by the control group. These results support the view that children with malignancies who are receiving chemotherapy should not be denied immunization with inactivated vaccines.", "contents": "Antibody responses in normal infants and in infants receiving chemotherapy for congenital neuroblastoma. Three infants with congenital neuroblastoma received a primary series of diptheria-pertassis-tetanus (DPT) immunizations during and after courses of chemotherapy with immunosuppressive medications. Serum IgG, IgA and IgM levels and antidiphthria and antitetanus antibody responses were measured and compared with those of normal infants of similar age. Protective levels of antibody were achieved by the study patients as well as by the control group. These results support the view that children with malignancies who are receiving chemotherapy should not be denied immunization with inactivated vaccines."}
{"id": "PMID:198095", "title": "Preliminary clinical results from U.S. fast neutron teletherapy studies.", "content": "Over 700 patients with cancer have been treated with fast neutron beams since 1972 in three U.S. programs at the M.D. Anderson-TAMVEC (Houston and College Station, Texas), University of Washington (Seattle, Washington), and MANTA (Naval Research Laboratory, Washington, D.C.). Clinical applications are about to start at the Fermilab (Batavia, Illinois) and Cleveland Clinic-NASA (Cleveland, Ohio). To date, studies have included: 1) effects of different treatment patterns and doses; 2) responses of several tumor types at many anatomic sites; and 3) acute and long-term normal tissue tolerances. Responses of several cancers, such as extensive epidermoid carcinoma of the cervix and \"fixed\" metastatic cervical adenopathy, have been encouraging. In patients with glioblastoma multiforme, good tumor responses have not lengthened survival compared with the following conventional radiation therapy. Both local tumor control and \"cure\" have been compromised by the inclusion of patients with very extensive cancers. In general, treatment has been well tolerated. These preliminary studies provide the basis for planned clinical trials.", "contents": "Preliminary clinical results from U.S. fast neutron teletherapy studies. Over 700 patients with cancer have been treated with fast neutron beams since 1972 in three U.S. programs at the M.D. Anderson-TAMVEC (Houston and College Station, Texas), University of Washington (Seattle, Washington), and MANTA (Naval Research Laboratory, Washington, D.C.). Clinical applications are about to start at the Fermilab (Batavia, Illinois) and Cleveland Clinic-NASA (Cleveland, Ohio). To date, studies have included: 1) effects of different treatment patterns and doses; 2) responses of several tumor types at many anatomic sites; and 3) acute and long-term normal tissue tolerances. Responses of several cancers, such as extensive epidermoid carcinoma of the cervix and \"fixed\" metastatic cervical adenopathy, have been encouraging. In patients with glioblastoma multiforme, good tumor responses have not lengthened survival compared with the following conventional radiation therapy. Both local tumor control and \"cure\" have been compromised by the inclusion of patients with very extensive cancers. In general, treatment has been well tolerated. These preliminary studies provide the basis for planned clinical trials."}
{"id": "PMID:198096", "title": "Breast carcinoma following radiotherapy of metastatic Wilm's tumor.", "content": "A 22-year-old women developed breast cancer 15 years after radiotherapy to the lung for metastatic Wilms tumor. Her 32-year-old mother died of bilateral breast cancer, suggesting a genetic predisposition to radiogenic cancer. Recent improvements in the survival of children with certain cancers necessitate long-term surveillance for iatrogenic neoplasia, particularly when familial susceptibility is evident.", "contents": "Breast carcinoma following radiotherapy of metastatic Wilm's tumor. A 22-year-old women developed breast cancer 15 years after radiotherapy to the lung for metastatic Wilms tumor. Her 32-year-old mother died of bilateral breast cancer, suggesting a genetic predisposition to radiogenic cancer. Recent improvements in the survival of children with certain cancers necessitate long-term surveillance for iatrogenic neoplasia, particularly when familial susceptibility is evident."}
{"id": "PMID:198098", "title": "Histopathological study of the first Medical Research Council Nephroblastoma Trial.", "content": "A histological analysis of the tumors from the first Medical Research Council (M.R.C.) Nephroblastoma Trial was carried out. Material from 104 out of the 111 concluded cases was suitable for assessment. The degree of tubular differentiation and the presence or absence of glomeruli, cysts and papillary structures were correlated with clinical stage and survival. A significant association was found with regard to tubular differentiation. Papillary structures appeared to be important, but the number of cases was small. The presence of either glomeruli or cysts was not a statistically significant feature as regards prognosis.", "contents": "Histopathological study of the first Medical Research Council Nephroblastoma Trial. A histological analysis of the tumors from the first Medical Research Council (M.R.C.) Nephroblastoma Trial was carried out. Material from 104 out of the 111 concluded cases was suitable for assessment. The degree of tubular differentiation and the presence or absence of glomeruli, cysts and papillary structures were correlated with clinical stage and survival. A significant association was found with regard to tubular differentiation. Papillary structures appeared to be important, but the number of cases was small. The presence of either glomeruli or cysts was not a statistically significant feature as regards prognosis."}
{"id": "PMID:198099", "title": "Hemostatic factors in primary hepatocellular cancer.", "content": "Detailed coagulation studies were performed in a group of 19 patients with primary hepatocellular cancer (PHC) and the results were compared statistically with the findings in 19 control subjects. Various funcitonal and immunochemical methods were employed in determining the possible presence of functional or structural coagulant protein abnormalities. The patient group was characterized by prolonged prothrombin  times, partial thromboplastin times, and Reptilase times, increased levels of fibrinogen, factor VIII, and factor VIII-related antigen, moderately devreased levels of factor V, factor IX, factor X, antithrombin III, and plasminogen, and reduced levels of factor II and factor VII. Functional, immunochemical, and biochemical analysis failed to detect the presence of acquired protein abnormalities. These findings indicate that hemostatic changes in primary hepatocellular cancer are nonspecific in character. Severe alterations in the plasma levels of one or more of these hemostatic factors may occur.", "contents": "Hemostatic factors in primary hepatocellular cancer. Detailed coagulation studies were performed in a group of 19 patients with primary hepatocellular cancer (PHC) and the results were compared statistically with the findings in 19 control subjects. Various funcitonal and immunochemical methods were employed in determining the possible presence of functional or structural coagulant protein abnormalities. The patient group was characterized by prolonged prothrombin  times, partial thromboplastin times, and Reptilase times, increased levels of fibrinogen, factor VIII, and factor VIII-related antigen, moderately devreased levels of factor V, factor IX, factor X, antithrombin III, and plasminogen, and reduced levels of factor II and factor VII. Functional, immunochemical, and biochemical analysis failed to detect the presence of acquired protein abnormalities. These findings indicate that hemostatic changes in primary hepatocellular cancer are nonspecific in character. Severe alterations in the plasma levels of one or more of these hemostatic factors may occur."}
{"id": "PMID:198100", "title": "HBAg-positive chronic liver disease associated with cirrhosis and hepatocellular carcinoma in the Senoi.", "content": "Necropsy and clinical data show that primary hepatocellular carcinoma (PHC) is the commonest cancer among the Senoi (a Malaysian aboringine group). The other aboringine tribes do not appear to have this high predilection for liver cancer. In the necropsy series, PHS was present in 10 out of 22 Senoi patients with cirrhosis. All the 22 livers contained hepatocytes that stained with Shikata's orcein stain and specific immunoperoxidase and immunofluorescent stains for hepatitis B antigen (HBAg). This observation raises the strong possibility that hepatitis B may be an important etiologic factor in the development of cirrhosis and PHC in the Senoi. The reason for the high susceptibility of the Senoi for HB virus infection is not clear, and the role of aflatoxin in the pathogenesis of PHC in the Senoi has yet to be determined. That the Senoi are a numerically small community, maintaining their own unique dietary and social customs and living in readily accessible areas in the Malaysian jungle, makes them an ideal population for the study of factors in the etiology of liver cancer.", "contents": "HBAg-positive chronic liver disease associated with cirrhosis and hepatocellular carcinoma in the Senoi. Necropsy and clinical data show that primary hepatocellular carcinoma (PHC) is the commonest cancer among the Senoi (a Malaysian aboringine group). The other aboringine tribes do not appear to have this high predilection for liver cancer. In the necropsy series, PHS was present in 10 out of 22 Senoi patients with cirrhosis. All the 22 livers contained hepatocytes that stained with Shikata's orcein stain and specific immunoperoxidase and immunofluorescent stains for hepatitis B antigen (HBAg). This observation raises the strong possibility that hepatitis B may be an important etiologic factor in the development of cirrhosis and PHC in the Senoi. The reason for the high susceptibility of the Senoi for HB virus infection is not clear, and the role of aflatoxin in the pathogenesis of PHC in the Senoi has yet to be determined. That the Senoi are a numerically small community, maintaining their own unique dietary and social customs and living in readily accessible areas in the Malaysian jungle, makes them an ideal population for the study of factors in the etiology of liver cancer."}
{"id": "PMID:198101", "title": "Direct immunochemical detection of prostaglandin-E and cyclic nucleotides in human malignant tumors.", "content": "Immunofluorescent localization of prostaglandin-E (PGE), cyclic AMP (CAMP), and cyclic GMP (cGMP) was studied in tumor tissues from 40 patients with a variety of solid tumors. Representative normal tissues served as controls. Rabbit antisera specific for PGE or the cyclic nucleotides were used, and the reactions observed were correlated with the degree and type of lymphocytic reaction at the tumor margins. Strong PGE immunofluorescence was detected in tumor cells in 27 of 42 malignancies; by contrast nine of 13 normal tissues showed weak PGE reactions, cAMP was detected in 30 of the 42 malignancies; cGMP was noted in only seven of the 42 malignant tissues and in none of the normal tissues studied. The most common malignant tumor profile (17/42) was that of positive PGE and cAMP and negative cGMP staining. Tumors showing strong staining with anti-PGE or cAMP demonstrated a distinct trend towards heavier lymphocytic infiltration with a predominance of T cells at their margins, although this association did not reach statistical significance in the present material.", "contents": "Direct immunochemical detection of prostaglandin-E and cyclic nucleotides in human malignant tumors. Immunofluorescent localization of prostaglandin-E (PGE), cyclic AMP (CAMP), and cyclic GMP (cGMP) was studied in tumor tissues from 40 patients with a variety of solid tumors. Representative normal tissues served as controls. Rabbit antisera specific for PGE or the cyclic nucleotides were used, and the reactions observed were correlated with the degree and type of lymphocytic reaction at the tumor margins. Strong PGE immunofluorescence was detected in tumor cells in 27 of 42 malignancies; by contrast nine of 13 normal tissues showed weak PGE reactions, cAMP was detected in 30 of the 42 malignancies; cGMP was noted in only seven of the 42 malignant tissues and in none of the normal tissues studied. The most common malignant tumor profile (17/42) was that of positive PGE and cAMP and negative cGMP staining. Tumors showing strong staining with anti-PGE or cAMP demonstrated a distinct trend towards heavier lymphocytic infiltration with a predominance of T cells at their margins, although this association did not reach statistical significance in the present material."}
{"id": "PMID:198102", "title": "Comparative epidemiology of carcinoid and oat-cell tumors of the lung.", "content": "Oat-cell carcinoma and bronchial carcinoid share histologic features with the Kultschitzky cell, and this argues for a common origin from the Kultschitzky cell for these tumors. In this view, the carcinoid represents the less malignant form and the oat-cell carcinoma the highly malignant adenocarcinoma of the colon, the epidemiologies of the benign and malignant forms of tumor arising from the same precursor are similar. However, the epidemiology of carcinoid tumor and that of oat-cell carcinoma are different. Although the ectopic production of hormones links the two kinds of tumor, it is also seen in other histologic types of lung carcinoma. Lung carcinoids occur in the genetic disorder of multiple endocrine adenomatosis, suggesting a genetic etiology for at least some carcinoids. This contrasts with the exogenous etiologic agents of cigarette smoking, occupational exposure, and urban domicile for oat-cell carcinoma. All these strong differences between lung carcinoid and oat-cell carcinoma indicate a markedly different process of carcinogenesis, which casts doubt on the hypothesis of a common cell precursor.", "contents": "Comparative epidemiology of carcinoid and oat-cell tumors of the lung. Oat-cell carcinoma and bronchial carcinoid share histologic features with the Kultschitzky cell, and this argues for a common origin from the Kultschitzky cell for these tumors. In this view, the carcinoid represents the less malignant form and the oat-cell carcinoma the highly malignant adenocarcinoma of the colon, the epidemiologies of the benign and malignant forms of tumor arising from the same precursor are similar. However, the epidemiology of carcinoid tumor and that of oat-cell carcinoma are different. Although the ectopic production of hormones links the two kinds of tumor, it is also seen in other histologic types of lung carcinoma. Lung carcinoids occur in the genetic disorder of multiple endocrine adenomatosis, suggesting a genetic etiology for at least some carcinoids. This contrasts with the exogenous etiologic agents of cigarette smoking, occupational exposure, and urban domicile for oat-cell carcinoma. All these strong differences between lung carcinoid and oat-cell carcinoma indicate a markedly different process of carcinogenesis, which casts doubt on the hypothesis of a common cell precursor."}
{"id": "PMID:198103", "title": "Multiple infiltrating glomus tumors in children.", "content": "Two children with  multiple infiltrating glomus tumors of the lower extremities presented in infancy with clinical and, in one, radiological, signs of varicose veins. Surgical therapy was followed by multiple recurrences, a phenomenon attributable to the infiltrative properties of the tumor. This variant of multiple glomus tumor may be congenital and is probably hamartomatous in nature.", "contents": "Multiple infiltrating glomus tumors in children. Two children with  multiple infiltrating glomus tumors of the lower extremities presented in infancy with clinical and, in one, radiological, signs of varicose veins. Surgical therapy was followed by multiple recurrences, a phenomenon attributable to the infiltrative properties of the tumor. This variant of multiple glomus tumor may be congenital and is probably hamartomatous in nature."}
{"id": "PMID:198104", "title": "Nine year follow-up of a case of benign liver cell adenoma related to oral contraceptives.", "content": "The case of a 26-year-old women on oral contraceptives who developed a benign liver cell adenoma that was successfully resected is reported. She continued on her oral medication and developed a recurrence 3 years later. On her second laparotomy, the liver tumor was merely biopsied and not removed. Oral contraceptive use was continued for an additional 3 years and then stopped. The tumor has regressed and is no longer palpable or diagnosable. The patient continues to be well 9 years following her first surgical procedure.", "contents": "Nine year follow-up of a case of benign liver cell adenoma related to oral contraceptives. The case of a 26-year-old women on oral contraceptives who developed a benign liver cell adenoma that was successfully resected is reported. She continued on her oral medication and developed a recurrence 3 years later. On her second laparotomy, the liver tumor was merely biopsied and not removed. Oral contraceptive use was continued for an additional 3 years and then stopped. The tumor has regressed and is no longer palpable or diagnosable. The patient continues to be well 9 years following her first surgical procedure."}
{"id": "PMID:198105", "title": "Benign liver-cell adenoma associated with long-term administration of an androgenic-anabolic steroid (methandienone).", "content": "A 19-year-old man with paroxysmal nocturnal hemoglobinuria treated for 3 years with Methandienone was admitted to the hospital with hemoperitoneum due to the rupture of an hepatic tumor. Histology revealed that it was a benign liver cell adenoma, with a pathologic appearance and mode of clinical presentation closely resembling those of cases observed to develop in association to contraceptive steroids.", "contents": "Benign liver-cell adenoma associated with long-term administration of an androgenic-anabolic steroid (methandienone). A 19-year-old man with paroxysmal nocturnal hemoglobinuria treated for 3 years with Methandienone was admitted to the hospital with hemoperitoneum due to the rupture of an hepatic tumor. Histology revealed that it was a benign liver cell adenoma, with a pathologic appearance and mode of clinical presentation closely resembling those of cases observed to develop in association to contraceptive steroids."}
{"id": "PMID:198106", "title": "Multiple hepatic adenomas and a hepatocellular carcinoma in a man on oral methyl testosterone for eleven years.", "content": "Numerous small hepatic adenomas and hepatocellular carcinoma developed in a man after 11 years of methyl testosterone ingestion. The man presented with an acute surgical abdomen and a large filling defect in the liver. Laparotomy disclosed hemoperitoneum and a large hepatic hematoma. Focal hemorrhagic infarction in the excised right liver lobe involved both adenomas and normal parenchyma. Review of the English literature reveals no other case of both a benign and a malignant hepatocellular neoplasm associated with anabolic steroid therapy. Hemorrhagic benign liver tumor must be considered in the differential diagnosis in both female and male patients on hormone therapy who present with acute abdominal pain.", "contents": "Multiple hepatic adenomas and a hepatocellular carcinoma in a man on oral methyl testosterone for eleven years. Numerous small hepatic adenomas and hepatocellular carcinoma developed in a man after 11 years of methyl testosterone ingestion. The man presented with an acute surgical abdomen and a large filling defect in the liver. Laparotomy disclosed hemoperitoneum and a large hepatic hematoma. Focal hemorrhagic infarction in the excised right liver lobe involved both adenomas and normal parenchyma. Review of the English literature reveals no other case of both a benign and a malignant hepatocellular neoplasm associated with anabolic steroid therapy. Hemorrhagic benign liver tumor must be considered in the differential diagnosis in both female and male patients on hormone therapy who present with acute abdominal pain."}
{"id": "PMID:198107", "title": "Experimental carcinogenesis: induction of multiple tumors by viruses.", "content": "Many viruses are able to cause the development of tumors when inoculated into suitable vertebrate hosts. Among them, polyoma virus can induce tumors in several mammalian species: not only many different kinds of tumor, but a large number of tumors within a single individual. Tissue culture studies employing cells from mice and hamsters, as well as observations of the manner of tumor development following polyoma virus injection in these species in vivo, suggest that some, or all, of the tumors so induced are multiple primaries. Because of the availability of mice of different genetic constitutions, the relative ease with which mouse cells from both normal and malignant tissue can cultivate in vitro, the known responses of mice to many carcinogenic agents, as well as the availability of transplantable, metastasizing mouse tumors, it is believed the polyoma virus/mouse host system would provide a highly suitable model in which an experimental approach to the elucidation of mechanisms for the origin of multiple tumors would be possible.", "contents": "Experimental carcinogenesis: induction of multiple tumors by viruses. Many viruses are able to cause the development of tumors when inoculated into suitable vertebrate hosts. Among them, polyoma virus can induce tumors in several mammalian species: not only many different kinds of tumor, but a large number of tumors within a single individual. Tissue culture studies employing cells from mice and hamsters, as well as observations of the manner of tumor development following polyoma virus injection in these species in vivo, suggest that some, or all, of the tumors so induced are multiple primaries. Because of the availability of mice of different genetic constitutions, the relative ease with which mouse cells from both normal and malignant tissue can cultivate in vitro, the known responses of mice to many carcinogenic agents, as well as the availability of transplantable, metastasizing mouse tumors, it is believed the polyoma virus/mouse host system would provide a highly suitable model in which an experimental approach to the elucidation of mechanisms for the origin of multiple tumors would be possible."}
{"id": "PMID:198108", "title": "Multiple primary tumors in domestic animals: a preliminary view with particular emphasis on tumors in dogs.", "content": "Cattle, horses, cats, and dogs with microscopically confirmed multiple primary tumors were reported to the Veterinary Medical Data Program, a system to collect, store and retrieve veterinary clinical information. Of 2611 tumors diagnosed prior to, concurrent with, or subsequent to other tumors during the period studied, 2361 were in 1062 dogs and 250 were in 120 other animals in all other species categories. The 604 multiple primary malignancies (two or more malignant tumors in one animal) were similarly distributed, by species, with 512 in dogs and 92 in all other species combined. The total number of multiple tumors reported in dogs closely approximated a theoretic model of random distribution, but several site-pairs of tumors seemed to occur excessively; one pair (mammary tumors and tumors of internal female organs) might parallel a similar excessive occurrence in women, suggesting a possible spontaneous tumor model for the latter.", "contents": "Multiple primary tumors in domestic animals: a preliminary view with particular emphasis on tumors in dogs. Cattle, horses, cats, and dogs with microscopically confirmed multiple primary tumors were reported to the Veterinary Medical Data Program, a system to collect, store and retrieve veterinary clinical information. Of 2611 tumors diagnosed prior to, concurrent with, or subsequent to other tumors during the period studied, 2361 were in 1062 dogs and 250 were in 120 other animals in all other species categories. The 604 multiple primary malignancies (two or more malignant tumors in one animal) were similarly distributed, by species, with 512 in dogs and 92 in all other species combined. The total number of multiple tumors reported in dogs closely approximated a theoretic model of random distribution, but several site-pairs of tumors seemed to occur excessively; one pair (mammary tumors and tumors of internal female organs) might parallel a similar excessive occurrence in women, suggesting a possible spontaneous tumor model for the latter."}
{"id": "PMID:198109", "title": "The epidemiology of oral cavity, pharyngeal and esophageal cancer outside of North America and Western Europe.", "content": "Geographical variations in the incidence of oral cavity, pharyngeal, and esophageal cancer were studied, with special reference to rates in countries outside of the United States and Western Europe. Although reporting techniques differ greatly and comparisons must be made with caution, significant variations are evident. Tracing such differences often reveals possible etiologic factor for these forms of cancer. The roles are discussed of known environmental carcinogens, such as N-nitroso compounds, polycyclic aromatic hydrocarbons, and such cultural habits as smoking or chewing tobacco, excessive consumption of alcoholic beverages, as well as other possible factors in the etiology of these cancer types.", "contents": "The epidemiology of oral cavity, pharyngeal and esophageal cancer outside of North America and Western Europe. Geographical variations in the incidence of oral cavity, pharyngeal, and esophageal cancer were studied, with special reference to rates in countries outside of the United States and Western Europe. Although reporting techniques differ greatly and comparisons must be made with caution, significant variations are evident. Tracing such differences often reveals possible etiologic factor for these forms of cancer. The roles are discussed of known environmental carcinogens, such as N-nitroso compounds, polycyclic aromatic hydrocarbons, and such cultural habits as smoking or chewing tobacco, excessive consumption of alcoholic beverages, as well as other possible factors in the etiology of these cancer types."}
{"id": "PMID:198110", "title": "Patterns of second malignant neoplasms in children.", "content": "A search of the records of 10 pediatric oncology centers revealed 102 children with more than one malignant neoplasm. In this group of 102 patients, all pediatric cancers were seen as initial lesions, but Wilms' tumor and retinoblastoma were over-represented and leukemia and brain tumors underrepresented. Survival variation as well as tumor susceptibility may be responsible for this disproportion. Osteosarcomas and chondrosarcomas were the most frequent second malignant neoplasms (SMN). Embryonal tumors were rare as SMN and adult-type tumors (carcinomas) appeared at earlier than expected ages, whether arising after irradiation or not related to that form of therapy. Radiation was associated with 69 SMN, genetic disease accounted for 27 SMN and both conditions were noted in 15 SMN. In the group of 21 patients for whom neither radiation nor a known genetic disorder could be implicated, there were three with colon carcinoma and glioma and five with leukemia or lymphoma and glioma. These combinations may reflect new tissue-specific hereditary cancer syndromes.", "contents": "Patterns of second malignant neoplasms in children. A search of the records of 10 pediatric oncology centers revealed 102 children with more than one malignant neoplasm. In this group of 102 patients, all pediatric cancers were seen as initial lesions, but Wilms' tumor and retinoblastoma were over-represented and leukemia and brain tumors underrepresented. Survival variation as well as tumor susceptibility may be responsible for this disproportion. Osteosarcomas and chondrosarcomas were the most frequent second malignant neoplasms (SMN). Embryonal tumors were rare as SMN and adult-type tumors (carcinomas) appeared at earlier than expected ages, whether arising after irradiation or not related to that form of therapy. Radiation was associated with 69 SMN, genetic disease accounted for 27 SMN and both conditions were noted in 15 SMN. In the group of 21 patients for whom neither radiation nor a known genetic disorder could be implicated, there were three with colon carcinoma and glioma and five with leukemia or lymphoma and glioma. These combinations may reflect new tissue-specific hereditary cancer syndromes."}
{"id": "PMID:198112", "title": "In vivo initiated rat liver carcinogenesis studied in vitro; formation of alcoholic hyaline-type bodies.", "content": "Epithelial liver cells isolated from rats after oral diethylnitrosamine administration were established in culture. When propagated in vitro for 2--3 months, over half the cells contained acentric nuclei and large juxtanuclear inclusions resembling the hyaline deposits (Mallory bodies) in cirrhotic livers of alcoholics. The morphological changes and disarrayed filaments in these bodies were retained on serial passages for many months. Cells inoculated into nude mice or newborn rats produced carcinomas from which cells with these abnormalities were reestablished in continuous culture.", "contents": "In vivo initiated rat liver carcinogenesis studied in vitro; formation of alcoholic hyaline-type bodies. Epithelial liver cells isolated from rats after oral diethylnitrosamine administration were established in culture. When propagated in vitro for 2--3 months, over half the cells contained acentric nuclei and large juxtanuclear inclusions resembling the hyaline deposits (Mallory bodies) in cirrhotic livers of alcoholics. The morphological changes and disarrayed filaments in these bodies were retained on serial passages for many months. Cells inoculated into nude mice or newborn rats produced carcinomas from which cells with these abnormalities were reestablished in continuous culture."}
{"id": "PMID:198113", "title": "Solubilisation of Epstein-Barr virus (EBV)-associated nuclear antigen from Raji cells and chromatin by treatment with various molarities of NaCl.", "content": "The solubilisation of Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) by treatment with various molarities of NaCl was investigated using the 125I--IgG absorption assay. Ninety percent of the antigenic activity detected using the 125I--IgG absorption assay was insoluble at 0.15 M NaCl. It could be rendered soluble by treatment with 2.0 M NaCl, but reprecipitated upon return to 0.15 M NaCl. EBNA was partially extracted from Raji chromatin by treatment with 0.35 M NaCl. The efficiency of extraction was increased by homogenisation in 2.0 M NaCl followed by dialysis to 0.35 M NaCl. The data demonstrate the close association of EBNA with Raji chromatin and suggest that it may be a chromatin-associated non-histone protein.", "contents": "Solubilisation of Epstein-Barr virus (EBV)-associated nuclear antigen from Raji cells and chromatin by treatment with various molarities of NaCl. The solubilisation of Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) by treatment with various molarities of NaCl was investigated using the 125I--IgG absorption assay. Ninety percent of the antigenic activity detected using the 125I--IgG absorption assay was insoluble at 0.15 M NaCl. It could be rendered soluble by treatment with 2.0 M NaCl, but reprecipitated upon return to 0.15 M NaCl. EBNA was partially extracted from Raji chromatin by treatment with 0.35 M NaCl. The efficiency of extraction was increased by homogenisation in 2.0 M NaCl followed by dialysis to 0.35 M NaCl. The data demonstrate the close association of EBNA with Raji chromatin and suggest that it may be a chromatin-associated non-histone protein."}
{"id": "PMID:198114", "title": "Effects of selenium on azo dye hepatocarcinogenesis.", "content": "Groups of male Sprague--Dawley rats were maintained on three regimens: I. basal diet plus 0.05% 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), II. same as I plus 6 ppm selenium (Na2SeO3) in the drinking water, and III. same as I plus 6 ppm selenium added to the diet in the form of a high selenium yeast. The 3'-MeDAB was incorporated in the diet for 8 weeks and then removed. The selenium supplements in Groups II and III were continued for an additional 4 weeks. At sacrifice the liver tumor incidence from was ascertained as the ratio of animals with tumors/total number of surviving animals per group. Selenium reduced the incidence  from 92% (11/12) in the Group I control, to 46% (7/15) in Group II and to 64% (9/14) in Group III.", "contents": "Effects of selenium on azo dye hepatocarcinogenesis. Groups of male Sprague--Dawley rats were maintained on three regimens: I. basal diet plus 0.05% 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), II. same as I plus 6 ppm selenium (Na2SeO3) in the drinking water, and III. same as I plus 6 ppm selenium added to the diet in the form of a high selenium yeast. The 3'-MeDAB was incorporated in the diet for 8 weeks and then removed. The selenium supplements in Groups II and III were continued for an additional 4 weeks. At sacrifice the liver tumor incidence from was ascertained as the ratio of animals with tumors/total number of surviving animals per group. Selenium reduced the incidence  from 92% (11/12) in the Group I control, to 46% (7/15) in Group II and to 64% (9/14) in Group III."}
{"id": "PMID:198115", "title": "Differences between the structural dynamics of plasma membranes of normal hamster lymphocytes and lymphoid cells neoplastically transformed by simian virus 40 as revealed by laser Raman spectroscopy.", "content": "The Raman spectra of highly purified plasma membranes from SV40-transformed GD248 lymphocytes have been compared with the spectra of the membranes of normal cells over the spectral region 100 cm-1 to 3010 cm-1. Striking differences between the two membrane categories were observed in the thermal response of the CH-stretching and acoustical regions. Analysis of CH-stretching shows that the membranes of normal cells exhibit a thermal transition centered at 7 degrees and approximately 5 degrees wide. The membranes of GD248 cells, in contrast, show a lipid transition centered at -5 degrees and 12-18 degrees wide. Analysis of the acoustical region yields equivalent results. The membrane proteins of normal membranes undergo a large thermotropic transition, starting at 39 degrees (sample temperatures), whereas this transition begins at 23 degrees with GD248 plasma membranes. The results suggest the possibility that SV40-specific membrane proteins may modify the collective thermotropic behavior of both normal membrane proteins and membrane lipids.", "contents": "Differences between the structural dynamics of plasma membranes of normal hamster lymphocytes and lymphoid cells neoplastically transformed by simian virus 40 as revealed by laser Raman spectroscopy. The Raman spectra of highly purified plasma membranes from SV40-transformed GD248 lymphocytes have been compared with the spectra of the membranes of normal cells over the spectral region 100 cm-1 to 3010 cm-1. Striking differences between the two membrane categories were observed in the thermal response of the CH-stretching and acoustical regions. Analysis of CH-stretching shows that the membranes of normal cells exhibit a thermal transition centered at 7 degrees and approximately 5 degrees wide. The membranes of GD248 cells, in contrast, show a lipid transition centered at -5 degrees and 12-18 degrees wide. Analysis of the acoustical region yields equivalent results. The membrane proteins of normal membranes undergo a large thermotropic transition, starting at 39 degrees (sample temperatures), whereas this transition begins at 23 degrees with GD248 plasma membranes. The results suggest the possibility that SV40-specific membrane proteins may modify the collective thermotropic behavior of both normal membrane proteins and membrane lipids."}
{"id": "PMID:198117", "title": "Characterization of L5178Y leukemic cells by phagocytosis, cytochemical methods, and membrane marker techniques.", "content": "Membrane marker techniques, endocytosis, and cytochemical methods were used to characterize L5178Y cells. L5178Y cells were found to have surface membrane immunoglobulin that typifies B-cells, and membrane receptors that are common to both B-cells and monocytes. L5178Y cells also have endocytic and enzymatic activities that are characteristic of monocytes. Thus L5178Y cells have the dual characteristics of B-cells and monocytes.", "contents": "Characterization of L5178Y leukemic cells by phagocytosis, cytochemical methods, and membrane marker techniques. Membrane marker techniques, endocytosis, and cytochemical methods were used to characterize L5178Y cells. L5178Y cells were found to have surface membrane immunoglobulin that typifies B-cells, and membrane receptors that are common to both B-cells and monocytes. L5178Y cells also have endocytic and enzymatic activities that are characteristic of monocytes. Thus L5178Y cells have the dual characteristics of B-cells and monocytes."}
{"id": "PMID:198118", "title": "Regulation of mammary tumor virus production by prolactin in BALB/cfC3H mouse normal mammary epithelial cells in vitro.", "content": "Hormonal regulation of mammary tumor virus (MTV) production, has been analyzed with normal mammary epithelial cells from chronically infected BALB/cfC3H mice. The effect of prolactin in terms of increased MTV production was not reproducibly observed in cells cultured in tissue culture dishes, whereas the cells grown on floating collagen gels consistently responded to prolactin in a dose-dependent manner. Of the three media tested. Dulbecco's modified Eagle's medium was found to be the best in terms of responsiveness to prolactin and in maximal MTV production. Specificity studies with other pituitary and placental hormones in place of prolactin have shown that both growth hormones and human placental lactogen can replace prolactin, whereas follicle-stimulating hormone, luteinizing hormone, and thyrotrophin were ineffective. Contrary to the mammary tumor systems, where it has been shown that insulin and glucocorticoid can maximally stimulate MTV production, these hormones alone elicited only a small response in the absence of prolactin in normal mammary epithelial cells. Although prolactin alone had very little effect by itself, its presence was necessary (permissive effect) in order for the glucocorticoids to be able to maximally stimulate MTV production in normal cells.", "contents": "Regulation of mammary tumor virus production by prolactin in BALB/cfC3H mouse normal mammary epithelial cells in vitro. Hormonal regulation of mammary tumor virus (MTV) production, has been analyzed with normal mammary epithelial cells from chronically infected BALB/cfC3H mice. The effect of prolactin in terms of increased MTV production was not reproducibly observed in cells cultured in tissue culture dishes, whereas the cells grown on floating collagen gels consistently responded to prolactin in a dose-dependent manner. Of the three media tested. Dulbecco's modified Eagle's medium was found to be the best in terms of responsiveness to prolactin and in maximal MTV production. Specificity studies with other pituitary and placental hormones in place of prolactin have shown that both growth hormones and human placental lactogen can replace prolactin, whereas follicle-stimulating hormone, luteinizing hormone, and thyrotrophin were ineffective. Contrary to the mammary tumor systems, where it has been shown that insulin and glucocorticoid can maximally stimulate MTV production, these hormones alone elicited only a small response in the absence of prolactin in normal mammary epithelial cells. Although prolactin alone had very little effect by itself, its presence was necessary (permissive effect) in order for the glucocorticoids to be able to maximally stimulate MTV production in normal cells."}
{"id": "PMID:198119", "title": "Isolation and some biochemical characteristics of nuclei from AH-66 hepatoma cells.", "content": "Cetylpyridinium chloride uniquely facilitated the isolation of nuclei from AH-66 hepatoma ascites cells in an isotonic medium without homogenization because of its strong solubilization of their plasma membranes, which were resistant to mechanical shearing with the commonly used nonionic detergents such as Triton X-100, Nonidet P-40, and Tween 80. Virtually all the nuclei in a population of AH-66 cells (10(6)/ml) can be isolated with 0.2% cetylpyridinium chloride. The isolated nuclei were free of adherent cytoplasm, maintained satisfactory morphology, and had high activity of nicotinamide adenine dinucleotide pyrophosphorylase. Two-dimensional polyacrylamide gel electrophoresis of the acid-soluble nuclear proteins of the AH-66 hepatoma nuclei isolated by the cetylpyridinium chloride procedure as well as by the citric acid procedure revealed that Spots Ac and C16-C18 were significantly intense in the gel pattern. Unexpectedly, Spot A10 was absent from the gel pattern of AH-66 hepatoma nuclei.", "contents": "Isolation and some biochemical characteristics of nuclei from AH-66 hepatoma cells. Cetylpyridinium chloride uniquely facilitated the isolation of nuclei from AH-66 hepatoma ascites cells in an isotonic medium without homogenization because of its strong solubilization of their plasma membranes, which were resistant to mechanical shearing with the commonly used nonionic detergents such as Triton X-100, Nonidet P-40, and Tween 80. Virtually all the nuclei in a population of AH-66 cells (10(6)/ml) can be isolated with 0.2% cetylpyridinium chloride. The isolated nuclei were free of adherent cytoplasm, maintained satisfactory morphology, and had high activity of nicotinamide adenine dinucleotide pyrophosphorylase. Two-dimensional polyacrylamide gel electrophoresis of the acid-soluble nuclear proteins of the AH-66 hepatoma nuclei isolated by the cetylpyridinium chloride procedure as well as by the citric acid procedure revealed that Spots Ac and C16-C18 were significantly intense in the gel pattern. Unexpectedly, Spot A10 was absent from the gel pattern of AH-66 hepatoma nuclei."}
{"id": "PMID:198120", "title": "Relationship between feline leukemia virus antigen expression and viral infectivity in blood, bone marrow, and saliva of cats.", "content": "Correlation was greater than 90% between feline leukemia virus (FeLV), group-specific antigen (GSA) in leukocytes, and viral infectivity (VI) in serum or plasma from 132 cats infected with either the Rickard strain of FeLV, the Snyder-Theilen strain of feline sarcoma virus, or field strains of FeLV. Detection of GSA in blood cells was at least as sensitive as detection of VI in serum. In 45% of FeLV GSA-positive cats inoculated with FeLV-Rickard strain, VI was detected in saliva. No saliva samples from GSA-negative cats had VI. Sequential bone marrow biopsies from 34 cats inoculated with Snyder-Theilen feline sarcoma virus indicated that the correlation between FeLV GSA in bone marrow cells and blood cells was virtually 100%. FeLV GSA appeared in bone marrow leukocyte precursors 1 week before its appearance in peripheral blood leukocytes in 50% of the cats. The FeLV GSA-positive state was transient (3 to 6 weeks) in 34% of the Snyder-Theilen feline sarcoma virus-inoculated cats.", "contents": "Relationship between feline leukemia virus antigen expression and viral infectivity in blood, bone marrow, and saliva of cats. Correlation was greater than 90% between feline leukemia virus (FeLV), group-specific antigen (GSA) in leukocytes, and viral infectivity (VI) in serum or plasma from 132 cats infected with either the Rickard strain of FeLV, the Snyder-Theilen strain of feline sarcoma virus, or field strains of FeLV. Detection of GSA in blood cells was at least as sensitive as detection of VI in serum. In 45% of FeLV GSA-positive cats inoculated with FeLV-Rickard strain, VI was detected in saliva. No saliva samples from GSA-negative cats had VI. Sequential bone marrow biopsies from 34 cats inoculated with Snyder-Theilen feline sarcoma virus indicated that the correlation between FeLV GSA in bone marrow cells and blood cells was virtually 100%. FeLV GSA appeared in bone marrow leukocyte precursors 1 week before its appearance in peripheral blood leukocytes in 50% of the cats. The FeLV GSA-positive state was transient (3 to 6 weeks) in 34% of the Snyder-Theilen feline sarcoma virus-inoculated cats."}
{"id": "PMID:198122", "title": "Inhibition of B-16 melanoma growth in vivo by a synthetic analog of prostaglandin E2.", "content": "The effect of systemic administration of 16,16-dimethyl prostaglandin E2-methyl ester (di-M-PGE2) on the growth of B-16 melanoma tumors has been studied in C57BL/6J mice. Daily i.p. injection of 5 mu of di-M-PGE2 commencing on the day of tumor inoculation with 10(5) and 10(6) viable cells delayed appearance of tumors; for the smaller tumor inoculum, it also increased median survival among treated mice from 23 to 33 days. Di-M-PGE2 treatment of mice with established tumors caused significant inhibition of tumor growth, as measured by a number of parameters including tumor diameters and volumes. At the time of sacrifice, di-M-PGE2-treated mice had tumors that were an average of 32% smaller (by weight), contained 60% fewer melanoma cells, and had higher concentrations of cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monophosphate (+225% and +100%, respectively).", "contents": "Inhibition of B-16 melanoma growth in vivo by a synthetic analog of prostaglandin E2. The effect of systemic administration of 16,16-dimethyl prostaglandin E2-methyl ester (di-M-PGE2) on the growth of B-16 melanoma tumors has been studied in C57BL/6J mice. Daily i.p. injection of 5 mu of di-M-PGE2 commencing on the day of tumor inoculation with 10(5) and 10(6) viable cells delayed appearance of tumors; for the smaller tumor inoculum, it also increased median survival among treated mice from 23 to 33 days. Di-M-PGE2 treatment of mice with established tumors caused significant inhibition of tumor growth, as measured by a number of parameters including tumor diameters and volumes. At the time of sacrifice, di-M-PGE2-treated mice had tumors that were an average of 32% smaller (by weight), contained 60% fewer melanoma cells, and had higher concentrations of cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monophosphate (+225% and +100%, respectively)."}
{"id": "PMID:198124", "title": "Reduction of streptozotocin toxicity by 3-O-methyl-D-glucose with enhancement of antitumor activity in murine L1210 leukemia.", "content": "3-O-Methyl-D-glucose (3-OMG), a nontoxic nonmetabolizable derivative of glucose, is effective in reducing the toxicity of streptozotocin (SZ). In mice the administration of 3-OMG prior to SZ increased the dose that killed 50% of the animals from 240 to 340 mg/kg. Furthermore, the combination of 3-OMG plus nicotinamide (also effective in reducing SZ toxicity) increased the dose that killed 50% of the animals to 540 mg/kg. In L1210 leukemic mice treated with SZ, there was a 2-fold increase in the median survival of animals pretreated with 3-OMG and a 3-fold increase in that of animals pretreated with the combination of 3-OMG and nicotinamide. Neither 3-OMG nor nicotinamide alone enhanced the survival of the leukemic mice. Pretreatment of normal mice with 3-OMG partially prevented the expected fall in hepatic nicotinamide adenine dinucleotide content. This study suggests that 3-OMG, by protecting normal tissue, will permit the administration of larger therapeutic doses of SZ in leukemic L1210 mice. The protective effect of 3-OMG against SZ toxicity appears to be partially mediated through conservation of the nicotinamide adenine dinucleotide content in the tissue.", "contents": "Reduction of streptozotocin toxicity by 3-O-methyl-D-glucose with enhancement of antitumor activity in murine L1210 leukemia. 3-O-Methyl-D-glucose (3-OMG), a nontoxic nonmetabolizable derivative of glucose, is effective in reducing the toxicity of streptozotocin (SZ). In mice the administration of 3-OMG prior to SZ increased the dose that killed 50% of the animals from 240 to 340 mg/kg. Furthermore, the combination of 3-OMG plus nicotinamide (also effective in reducing SZ toxicity) increased the dose that killed 50% of the animals to 540 mg/kg. In L1210 leukemic mice treated with SZ, there was a 2-fold increase in the median survival of animals pretreated with 3-OMG and a 3-fold increase in that of animals pretreated with the combination of 3-OMG and nicotinamide. Neither 3-OMG nor nicotinamide alone enhanced the survival of the leukemic mice. Pretreatment of normal mice with 3-OMG partially prevented the expected fall in hepatic nicotinamide adenine dinucleotide content. This study suggests that 3-OMG, by protecting normal tissue, will permit the administration of larger therapeutic doses of SZ in leukemic L1210 mice. The protective effect of 3-OMG against SZ toxicity appears to be partially mediated through conservation of the nicotinamide adenine dinucleotide content in the tissue."}
{"id": "PMID:198125", "title": "Inhibition of normal lymphocyte mitogenic reactivity by serum from feline leukemia virus-infected cats.", "content": "The effect of serum from 12 cats with lymphosarcoma induced by feline leukemia virus (FeLV) on the response of normal cat peripheral blood lymphocytes to phytomitogen-induced blastogenesis was studied. The majority of FeLV sera, when tested at a concentration of 20% of the incubation medium, caused a 40 to 70% reduction in the mean blastogenic response to concanavalin A compared to the response obtained with a similar concentration of normal feline serum. Results with pokeweed mitogen were similar, but the depression in blastogenesis was less than with concanavalin A. Further studies showed that the blastogenic inhibitory activity of FeLV serum (a) was heat labile at 56 degrees for 30 min, (b) could not be overcome by greater concentrations of mitogens, (c) was proportional to the concentration of FeLV serum in the incubation medium, and (d) could not be demonstrated when lymphocytes were preincubated in FeLV serum followed by washing and reincubating in normal feline serum. The results suggested that a substance present in the serum of FeLV-infected cats contributes to altered immunological reactivity during leukemogenesis in the cat.", "contents": "Inhibition of normal lymphocyte mitogenic reactivity by serum from feline leukemia virus-infected cats. The effect of serum from 12 cats with lymphosarcoma induced by feline leukemia virus (FeLV) on the response of normal cat peripheral blood lymphocytes to phytomitogen-induced blastogenesis was studied. The majority of FeLV sera, when tested at a concentration of 20% of the incubation medium, caused a 40 to 70% reduction in the mean blastogenic response to concanavalin A compared to the response obtained with a similar concentration of normal feline serum. Results with pokeweed mitogen were similar, but the depression in blastogenesis was less than with concanavalin A. Further studies showed that the blastogenic inhibitory activity of FeLV serum (a) was heat labile at 56 degrees for 30 min, (b) could not be overcome by greater concentrations of mitogens, (c) was proportional to the concentration of FeLV serum in the incubation medium, and (d) could not be demonstrated when lymphocytes were preincubated in FeLV serum followed by washing and reincubating in normal feline serum. The results suggested that a substance present in the serum of FeLV-infected cats contributes to altered immunological reactivity during leukemogenesis in the cat."}
{"id": "PMID:198127", "title": "Hepatocarcinogenic effects of N-nitroso-N-methylurea in guinea pigs.", "content": "Intragastric administration of N-nitroso-N-methylurea to strain 13 male guinea pigs, at a weekly dosage of 7.5 mg/kg for 15 weeks and then twice weekly for a subsequent 15 weeks, induced high toxicity, as evidenced by weight loss and mortality and a high incidence of malignant neoplasms, over a total observational period of 40 weeks. The neoplasms included hepatic angiosarcomas, cholangiocarcinomas, and generalized lymphoblastic lymphomas.", "contents": "Hepatocarcinogenic effects of N-nitroso-N-methylurea in guinea pigs. Intragastric administration of N-nitroso-N-methylurea to strain 13 male guinea pigs, at a weekly dosage of 7.5 mg/kg for 15 weeks and then twice weekly for a subsequent 15 weeks, induced high toxicity, as evidenced by weight loss and mortality and a high incidence of malignant neoplasms, over a total observational period of 40 weeks. The neoplasms included hepatic angiosarcomas, cholangiocarcinomas, and generalized lymphoblastic lymphomas."}
{"id": "PMID:198128", "title": "Fetal infection with bovine leukemia virus in sheep.", "content": "Several sheep fetuses were thymectomized, and their tails were removed at 58 to 65 days of gestation for tissue culture. Bovine leukemia virus (BLV) antigens were detected in serial culture of tissues from fetuses whose dams and sires were both BLV positive. However, no BLV antigens were detected in serial cultures of tissues from fetuses whose dams were negative but whose sire was positive. Precolostral serums from 3 of 16 neonatal lambs, whose sire and dams were both BLV positive, were BLV antibody positive. Thus, BLV may be vertically transmitted from a positive dam to her lamb via the placenta and/or germinal cells but not from sire to lamb.", "contents": "Fetal infection with bovine leukemia virus in sheep. Several sheep fetuses were thymectomized, and their tails were removed at 58 to 65 days of gestation for tissue culture. Bovine leukemia virus (BLV) antigens were detected in serial culture of tissues from fetuses whose dams and sires were both BLV positive. However, no BLV antigens were detected in serial cultures of tissues from fetuses whose dams were negative but whose sire was positive. Precolostral serums from 3 of 16 neonatal lambs, whose sire and dams were both BLV positive, were BLV antibody positive. Thus, BLV may be vertically transmitted from a positive dam to her lamb via the placenta and/or germinal cells but not from sire to lamb."}
{"id": "PMID:198129", "title": "Detection and evaluation of feline oncornavirus-induced cell surface antigen(s) shed from cells in vitro.", "content": "A method for preparation of soluble feline oncornavirus-induced cell surface antigens was described. This technique relied upon the natural release of antigen(s) from FL-74 feline lymphoblastoid cells during their maintenance at 37 degrees in serum-deficient medium. When concentrated and clarified spent medium from 4-day cultures was tested for its antigen content by inhibition of humoral cytotoxicity, it was found that this  natural production of soluble antigen provided more feline oncornavirus-associated cell membrane antigen per cell than did a solubilization procedure in which papain was used. The shed antigen preparation was immunogenic in cats, eliciting humoral antibody that was reactive with the surface of FL-74 Cells and feline sarcoma virus-transformed nonproducer mink cells but was not reactive with feline leukemia virus in a virus neutralization assay.", "contents": "Detection and evaluation of feline oncornavirus-induced cell surface antigen(s) shed from cells in vitro. A method for preparation of soluble feline oncornavirus-induced cell surface antigens was described. This technique relied upon the natural release of antigen(s) from FL-74 feline lymphoblastoid cells during their maintenance at 37 degrees in serum-deficient medium. When concentrated and clarified spent medium from 4-day cultures was tested for its antigen content by inhibition of humoral cytotoxicity, it was found that this  natural production of soluble antigen provided more feline oncornavirus-associated cell membrane antigen per cell than did a solubilization procedure in which papain was used. The shed antigen preparation was immunogenic in cats, eliciting humoral antibody that was reactive with the surface of FL-74 Cells and feline sarcoma virus-transformed nonproducer mink cells but was not reactive with feline leukemia virus in a virus neutralization assay."}
{"id": "PMID:198130", "title": "Magnitude of malate-aspartate reduced nicotinamide adenine dinucleotide shuttle activity in intact respiring tumor cells.", "content": "Measurements of respiration, CO2 and lactate production, and changes in the levels of various key metabolites of the glycolytic sequence and tricarboxylic acid cycle were made on five lines of rodent ascites tumor cells (two strains of Ehrlich ascites tumor cells, Krebs II carcinoma, AS-30D carcinoma, and L1210 cells) incubated aerobically in the presence of uniformly labeled D-[14C]glucose. From these data, as well as earlier evidence demonstrating that the reduced nicotinamide adenine dinucleotide (NADH) shuttle in these cells requires a transaminase step and is thus identified as the malate-aspartate shuttle (W.V.V. Greenhouse and A.L. Lehninger, Cancer Res., 36: 1392-1396, 1976), metabolic flux diagrams were constructed for the five cell lines. These diagrams show the relative rates of glycolysis, the tricarboxylic acid cycle, electron transport, and the malate-aspartate shuttle in these tumors. Large amounts of cytosolic NADH were oxidized by the mitochondrial respiratory chain via the NADH shuttle, comprising anywhere from about 20 to 80% of the total flow of reducing equivalents to oxygen in these tumors. Calculations of the sources of energy for adenosine triphosphate synthesis indicated that on the average about one-third of the respiratory adenosine triphosphate is generated by electron flow originating from cytosolic NADH via the malate-aspartate shuttle.", "contents": "Magnitude of malate-aspartate reduced nicotinamide adenine dinucleotide shuttle activity in intact respiring tumor cells. Measurements of respiration, CO2 and lactate production, and changes in the levels of various key metabolites of the glycolytic sequence and tricarboxylic acid cycle were made on five lines of rodent ascites tumor cells (two strains of Ehrlich ascites tumor cells, Krebs II carcinoma, AS-30D carcinoma, and L1210 cells) incubated aerobically in the presence of uniformly labeled D-[14C]glucose. From these data, as well as earlier evidence demonstrating that the reduced nicotinamide adenine dinucleotide (NADH) shuttle in these cells requires a transaminase step and is thus identified as the malate-aspartate shuttle (W.V.V. Greenhouse and A.L. Lehninger, Cancer Res., 36: 1392-1396, 1976), metabolic flux diagrams were constructed for the five cell lines. These diagrams show the relative rates of glycolysis, the tricarboxylic acid cycle, electron transport, and the malate-aspartate shuttle in these tumors. Large amounts of cytosolic NADH were oxidized by the mitochondrial respiratory chain via the NADH shuttle, comprising anywhere from about 20 to 80% of the total flow of reducing equivalents to oxygen in these tumors. Calculations of the sources of energy for adenosine triphosphate synthesis indicated that on the average about one-third of the respiratory adenosine triphosphate is generated by electron flow originating from cytosolic NADH via the malate-aspartate shuttle."}
{"id": "PMID:198135", "title": "Investigations on the turnover of adrenocortical mitochondria. IX. A stereological study of the effects of chronic treatment with acth on the size and number of mitochondria from adult human adrenocortical cells cultured in vitro.", "content": "The effects of ACTH on the mitochondria of adult human adrenocortical cells cultured in vitro were investigated by electron microscopic and stereological methods. It was found that ACTH induces increase in the volume of the mitochondrial compartment, which is due to both a hypertrophy and an increase in number of the organelles. The hypothesis that ACTH controls the growth and proliferation of human adrenocortical mitochondria is discussed.", "contents": "Investigations on the turnover of adrenocortical mitochondria. IX. A stereological study of the effects of chronic treatment with acth on the size and number of mitochondria from adult human adrenocortical cells cultured in vitro. The effects of ACTH on the mitochondria of adult human adrenocortical cells cultured in vitro were investigated by electron microscopic and stereological methods. It was found that ACTH induces increase in the volume of the mitochondrial compartment, which is due to both a hypertrophy and an increase in number of the organelles. The hypothesis that ACTH controls the growth and proliferation of human adrenocortical mitochondria is discussed."}
{"id": "PMID:198137", "title": "On the occurrence of Merkel cells in the epidermis of teleost fishes.", "content": "The ultrastructure of a differentiated cell type in the epidermis of two species of teleost fish, Ictalurus melas and Phoxinus phoxinus, is described. This cell type has a synaptic association with nerve fibres, microvillus-like peripheral processes, and membrane-bounded inclusions, which together are the diagnostic features of the Merkel cells of tetrapod vertebrates. Other cytoplasmic features are shared with the epithelial cells. The appearance of the membrane-bounded granules depends on the fixative used; after fixation with glutaraldehyde the granules are of a size and electron-density comparable to that found in tetrapod Merkel cells, but after fixing in osmium tetroxide the granules are inconspicuous.", "contents": "On the occurrence of Merkel cells in the epidermis of teleost fishes. The ultrastructure of a differentiated cell type in the epidermis of two species of teleost fish, Ictalurus melas and Phoxinus phoxinus, is described. This cell type has a synaptic association with nerve fibres, microvillus-like peripheral processes, and membrane-bounded inclusions, which together are the diagnostic features of the Merkel cells of tetrapod vertebrates. Other cytoplasmic features are shared with the epithelial cells. The appearance of the membrane-bounded granules depends on the fixative used; after fixation with glutaraldehyde the granules are of a size and electron-density comparable to that found in tetrapod Merkel cells, but after fixing in osmium tetroxide the granules are inconspicuous."}
{"id": "PMID:198138", "title": "Coupled transcription-translation of DNA injected into Xenopus oocytes.", "content": "A previous report from this laboratory showed that purified DNAs are transcribed after injection into the nucleus of Xenopus laevis oocytes (Mertz and Gurdon, 1977). Here we demonstrate that at least some of the RNA synthesized is translated within these injected cells to produce the correct protein products. Injection of Simian Virus 40 DNA into oocytes induces the synthesis of at least two proteins not normally synthesized in these cells. Using two-dimensional polyacrylamide gel electrophoresis and well characterized deletion mutants of SV40 that produce proteins of smaller size, we show that these two proteins are, indeed, the virus-coded proteins VP1 and VP3. Synthesis of VP1 and VP3 is inhibited by alpha-amanitin and, therefore, presumably mediated by a type II RNA polymerase. We also present evidence indicating that a histone-like protein is induced after the injection of a cloned plasmid DNA that codes for the Drosophila melanogaster histone proteins. This in vivo coupled transcription-translation system should be useful for identifying and mapping proteins coded by cloned eucaryotic DNAs.", "contents": "Coupled transcription-translation of DNA injected into Xenopus oocytes. A previous report from this laboratory showed that purified DNAs are transcribed after injection into the nucleus of Xenopus laevis oocytes (Mertz and Gurdon, 1977). Here we demonstrate that at least some of the RNA synthesized is translated within these injected cells to produce the correct protein products. Injection of Simian Virus 40 DNA into oocytes induces the synthesis of at least two proteins not normally synthesized in these cells. Using two-dimensional polyacrylamide gel electrophoresis and well characterized deletion mutants of SV40 that produce proteins of smaller size, we show that these two proteins are, indeed, the virus-coded proteins VP1 and VP3. Synthesis of VP1 and VP3 is inhibited by alpha-amanitin and, therefore, presumably mediated by a type II RNA polymerase. We also present evidence indicating that a histone-like protein is induced after the injection of a cloned plasmid DNA that codes for the Drosophila melanogaster histone proteins. This in vivo coupled transcription-translation system should be useful for identifying and mapping proteins coded by cloned eucaryotic DNAs."}
{"id": "PMID:198139", "title": "A novel method to map transcripts: evidence for homology between an adenovirus mRNA and discrete multiple regions of the viral genome.", "content": "A method has been devised which permits mapping of transcripts by a two-step hybridization procedure (sandwich hybridization). RNA extracted from cells infected with an adenovirus-SV40 hybrid (Ad2+ND1) was hybridized to restriction endonuclease fragments of adenovirus type 2 (Ad2) DNA immobilized on nitrocellulose filters. RNAs containing both Ad2 and SV40 sequences formed duplexes through their Ad2 sequences, leaving their SV40 sequences as protruding tails. Annealing with 32P-labeled SV40 DNA caused these tails to become labeled, permitting autoradiographic identification of the sequences of Ad2 DNA which are homologous to the RNA. The high sensitivity of this technique, achieved through the use of 32P-labeled RNA of high specific activity, has led to the observation that hybridization of Ad2+ND1 RNA occurs at several locations on the Ad2 genome, in addition to the expected sites of hybridization proximal to the SV40 insertion.", "contents": "A novel method to map transcripts: evidence for homology between an adenovirus mRNA and discrete multiple regions of the viral genome. A method has been devised which permits mapping of transcripts by a two-step hybridization procedure (sandwich hybridization). RNA extracted from cells infected with an adenovirus-SV40 hybrid (Ad2+ND1) was hybridized to restriction endonuclease fragments of adenovirus type 2 (Ad2) DNA immobilized on nitrocellulose filters. RNAs containing both Ad2 and SV40 sequences formed duplexes through their Ad2 sequences, leaving their SV40 sequences as protruding tails. Annealing with 32P-labeled SV40 DNA caused these tails to become labeled, permitting autoradiographic identification of the sequences of Ad2 DNA which are homologous to the RNA. The high sensitivity of this technique, achieved through the use of 32P-labeled RNA of high specific activity, has led to the observation that hybridization of Ad2+ND1 RNA occurs at several locations on the Ad2 genome, in addition to the expected sites of hybridization proximal to the SV40 insertion."}
{"id": "PMID:198142", "title": "Avian myeloblastosis virus RNA is terminally redundant: implications for the mechanism of retrovirus replication.", "content": "We have determined the terminal heteropolymeric sequences of AMV RNA by the following procedures: first, RNA sequence determination on the 5' terminal and the poly(A)-linked 3' terminal T1 oligonucleotides, and second, analysis by the Maxam and Gilbert (1977) method of AMV strong stop DNA and of DNA complementary to the poly(A)-linked T1 oligonucleotide, synthesized with reverse transcriptase and (pdT)13 as primer. The structure deduced for the 5' terminal region is (5')7mGpppGmCCAUUCUACCUCUCACCACAUUGGUGUGCACCUGGGUUGAUGGCCGGACCGUCGAUUCCCUGACGACUACGAGCACCUGCAUGAAGCAGAAGGCUUCAU... Two distinct 3' terminal sequences were deduced: GCCAUUCUACCUCUCAAA...AOH and GCCAUUCUACCUCUCACCAAA...AOH. The two termini, differing by a C-C-A sequence, may reflect genetic heterogeneity of the AMV stock or, more probably, may be generated at or after RNA transcription. These results demonstrate a terminal redundancy of the hetero polymeric sequence of 16 and 19 nucleotides, respectively. The terminal redundancy allows for mechanisms which involve transfer of the DNA segment synthesized on the 5' terminal redundant sequence to the 3' terminal redundant sequence.", "contents": "Avian myeloblastosis virus RNA is terminally redundant: implications for the mechanism of retrovirus replication. We have determined the terminal heteropolymeric sequences of AMV RNA by the following procedures: first, RNA sequence determination on the 5' terminal and the poly(A)-linked 3' terminal T1 oligonucleotides, and second, analysis by the Maxam and Gilbert (1977) method of AMV strong stop DNA and of DNA complementary to the poly(A)-linked T1 oligonucleotide, synthesized with reverse transcriptase and (pdT)13 as primer. The structure deduced for the 5' terminal region is (5')7mGpppGmCCAUUCUACCUCUCACCACAUUGGUGUGCACCUGGGUUGAUGGCCGGACCGUCGAUUCCCUGACGACUACGAGCACCUGCAUGAAGCAGAAGGCUUCAU... Two distinct 3' terminal sequences were deduced: GCCAUUCUACCUCUCAAA...AOH and GCCAUUCUACCUCUCACCAAA...AOH. The two termini, differing by a C-C-A sequence, may reflect genetic heterogeneity of the AMV stock or, more probably, may be generated at or after RNA transcription. These results demonstrate a terminal redundancy of the hetero polymeric sequence of 16 and 19 nucleotides, respectively. The terminal redundancy allows for mechanisms which involve transfer of the DNA segment synthesized on the 5' terminal redundant sequence to the 3' terminal redundant sequence."}
{"id": "PMID:198143", "title": "Inhibition of viral protein synthesis in monkey cells treated with interferon late in simian virus 40 lytic cycle.", "content": "We have investigated the effect of interferon on SV40 gene expression late in the lytic cycle, after early functions have been expressed and viral DNA replication has been initiated. Whereas pretreatment with interferon prior to infection reduces the amount of early SV40 RNA, post-infection treatment does not inhibit viral RNA synthesis. Viral 19S and 16S RNA species are found undiminished in quantity and poly(A) content. Despite the apparent normalcy of viral RNA classes, however, there is a marked reduction in the synthesis of their protein products, both T antigen and capsid polypeptides. The association of viral RNA with heavy polyribosomes is strongly reduced. On the other hand, there is no degradation of nonviral polyribosomes and the synthesis of most cellular proteins continues. These experiments demonstrate that late in infection, interferon treatment results in an inhibition of viral mRNA translation.", "contents": "Inhibition of viral protein synthesis in monkey cells treated with interferon late in simian virus 40 lytic cycle. We have investigated the effect of interferon on SV40 gene expression late in the lytic cycle, after early functions have been expressed and viral DNA replication has been initiated. Whereas pretreatment with interferon prior to infection reduces the amount of early SV40 RNA, post-infection treatment does not inhibit viral RNA synthesis. Viral 19S and 16S RNA species are found undiminished in quantity and poly(A) content. Despite the apparent normalcy of viral RNA classes, however, there is a marked reduction in the synthesis of their protein products, both T antigen and capsid polypeptides. The association of viral RNA with heavy polyribosomes is strongly reduced. On the other hand, there is no degradation of nonviral polyribosomes and the synthesis of most cellular proteins continues. These experiments demonstrate that late in infection, interferon treatment results in an inhibition of viral mRNA translation."}
{"id": "PMID:198150", "title": "Double viral infection of the mouth in the cancer patient.", "content": "An autopsy case of renal cancer complicated with multiple oral ulcers is presented. Although serological tests were not available, double viral infection with herpes simplex virus and cytomegalovirus was suspected as causal agents in the retrospective examination. This infection may be a complication in the prolonged stage of cancer patients.", "contents": "Double viral infection of the mouth in the cancer patient. An autopsy case of renal cancer complicated with multiple oral ulcers is presented. Although serological tests were not available, double viral infection with herpes simplex virus and cytomegalovirus was suspected as causal agents in the retrospective examination. This infection may be a complication in the prolonged stage of cancer patients."}
{"id": "PMID:198151", "title": "[Changes in the blood cortisol levels during the first week of life in calves (Bos taurus) and lambs (Ovis aries)].", "content": "At birth, the plasmatic level of cortisol is very variable and very high in the new-born Calf or the newborn Lamb. This level diminishes within one day and then varies between 10 and 30 ng/ml during the six following days. In the Calf, the secretion of cortisol can be directly stimulated by ACTH or inhibited at the level of the hypothalamic and hypophyseal system with dexamethasone on the day following birth.", "contents": "[Changes in the blood cortisol levels during the first week of life in calves (Bos taurus) and lambs (Ovis aries)]. At birth, the plasmatic level of cortisol is very variable and very high in the new-born Calf or the newborn Lamb. This level diminishes within one day and then varies between 10 and 30 ng/ml during the six following days. In the Calf, the secretion of cortisol can be directly stimulated by ACTH or inhibited at the level of the hypothalamic and hypophyseal system with dexamethasone on the day following birth."}
{"id": "PMID:198152", "title": "[The replication of a xenotropic murine C type virus in some mammalian cells. Definition of a specific antigen].", "content": "The use of our mink cell line maintained in vitro infected with the murine xenotropic AT 124 virus, and that of a (W/Fu x bn) f1 rat anti-124 serum allow us to define a new cell surface antigen specific of murine xenotropic type C viruses.", "contents": "[The replication of a xenotropic murine C type virus in some mammalian cells. Definition of a specific antigen]. The use of our mink cell line maintained in vitro infected with the murine xenotropic AT 124 virus, and that of a (W/Fu x bn) f1 rat anti-124 serum allow us to define a new cell surface antigen specific of murine xenotropic type C viruses."}
{"id": "PMID:198153", "title": "[Expression of an antigen associated with Gross virus on the surfaces of murine cells producing an oncornavirus from the radioleukemia of C57BL/6 mice].", "content": "A leukemogenic viral complex was demonstrated in cultures of 13-3 C cell line derived from a C57BL/6, radiation leukemia virus (RadLV-Rs) induced tumor. Both 13-3C and leukemic cells induced in C57BL/6 mice by 13-3C virus carry a cell surface antigen associated with Gross leukemia virus (GCSAa). These findings point to a close similarity between these antigens and those of murine endogenous ecotropic viruses.", "contents": "[Expression of an antigen associated with Gross virus on the surfaces of murine cells producing an oncornavirus from the radioleukemia of C57BL/6 mice]. A leukemogenic viral complex was demonstrated in cultures of 13-3 C cell line derived from a C57BL/6, radiation leukemia virus (RadLV-Rs) induced tumor. Both 13-3C and leukemic cells induced in C57BL/6 mice by 13-3C virus carry a cell surface antigen associated with Gross leukemia virus (GCSAa). These findings point to a close similarity between these antigens and those of murine endogenous ecotropic viruses."}
{"id": "PMID:198154", "title": "[Electrophoretic analysis of lactate NAD oxidoreductase in interspecific hybrids between three species of the genus Sphaeroma: S. monodi, S. Rugicauda and S. hookeri].", "content": "The electrophoretic analysis of lactate NAD oxydoreductase in interspecific hybrids between three species of genus Sphaeroma (S. monodi, S. rugicauda and S. hookeri hookeri) leads, for each category of hybrids, to a distribution between the two parental enzymatic patterns and, consequently, shows the absence of an isozyme appropriate to these hybrids.", "contents": "[Electrophoretic analysis of lactate NAD oxidoreductase in interspecific hybrids between three species of the genus Sphaeroma: S. monodi, S. Rugicauda and S. hookeri]. The electrophoretic analysis of lactate NAD oxydoreductase in interspecific hybrids between three species of genus Sphaeroma (S. monodi, S. rugicauda and S. hookeri hookeri) leads, for each category of hybrids, to a distribution between the two parental enzymatic patterns and, consequently, shows the absence of an isozyme appropriate to these hybrids."}
{"id": "PMID:198155", "title": "[Compared expression of murine plasmacytoma associated virus in tumor cells and in mouse embryo cells].", "content": "A DNA complementary to the viral genome of C-type particles produced by a Mouse myeloma derived cell line (MF2 cell line) was synthesized. This cDNA was used as a probe to study the viral genome expression among the total RNA and the poly (A)-rich RNA extracted from the MF2 and Balb/c embryonic cells. As evidenced by molecular hybridization experiments, the presence of at least one endogenous Balb/c virus in the MF2 virus stocks is suggested. In the productive cells, the viral RNA sequences are expressed in the poly (A)-rich RNA fraction.", "contents": "[Compared expression of murine plasmacytoma associated virus in tumor cells and in mouse embryo cells]. A DNA complementary to the viral genome of C-type particles produced by a Mouse myeloma derived cell line (MF2 cell line) was synthesized. This cDNA was used as a probe to study the viral genome expression among the total RNA and the poly (A)-rich RNA extracted from the MF2 and Balb/c embryonic cells. As evidenced by molecular hybridization experiments, the presence of at least one endogenous Balb/c virus in the MF2 virus stocks is suggested. In the productive cells, the viral RNA sequences are expressed in the poly (A)-rich RNA fraction."}
{"id": "PMID:198156", "title": "[Sensitivity of transformed EHSVi fibroblasts to the antibody-complement lytic system. Cooperation between the lytic units, and existence of a cellular defense].", "content": "The sensitivity of transformed EHSVi fibroblasts to the antibody-complement lytic system was evaluated, at various antibody concentrations (Ac), in conditions in which a variation of the lytic activity proportional to Ac3, 1 may be observed. This points out, not the expected cooperation between IgG molecules in activating C1 within a definite lytic unit, but a cooperation between the lytic units themselves, and therefore the existence of a cell defence.", "contents": "[Sensitivity of transformed EHSVi fibroblasts to the antibody-complement lytic system. Cooperation between the lytic units, and existence of a cellular defense]. The sensitivity of transformed EHSVi fibroblasts to the antibody-complement lytic system was evaluated, at various antibody concentrations (Ac), in conditions in which a variation of the lytic activity proportional to Ac3, 1 may be observed. This points out, not the expected cooperation between IgG molecules in activating C1 within a definite lytic unit, but a cooperation between the lytic units themselves, and therefore the existence of a cell defence."}
{"id": "PMID:198158", "title": "[3'5'-Cyclic AMP phosphodiesterase activity in the internal and external layers of human myometrium at the end of pregnancy].", "content": "The hydrolysis of cAMP by phosphodiesterase was studied in whole homogenate from human myometrium at the end of the pregnancy before onset of labour. Tissue samples were taken from outer and inner layers of placental and anti-placental sites. Kinetic analysis shows in every case two apparent Km values for low and high cAMP concentrations in the order of 1 x 10(-5) M and 1 x 10(-4) M. On the other hand Vmax values are lower for the enzyme isolated from the placental site than for the one isolated from the anti-placental area. In the 4 zones studied, an appreciable proportion of the low Km enzyme is present.", "contents": "[3'5'-Cyclic AMP phosphodiesterase activity in the internal and external layers of human myometrium at the end of pregnancy]. The hydrolysis of cAMP by phosphodiesterase was studied in whole homogenate from human myometrium at the end of the pregnancy before onset of labour. Tissue samples were taken from outer and inner layers of placental and anti-placental sites. Kinetic analysis shows in every case two apparent Km values for low and high cAMP concentrations in the order of 1 x 10(-5) M and 1 x 10(-4) M. On the other hand Vmax values are lower for the enzyme isolated from the placental site than for the one isolated from the anti-placental area. In the 4 zones studied, an appreciable proportion of the low Km enzyme is present."}
{"id": "PMID:198159", "title": "[Heterotransplantation of human glioblastoma in the brain of newborn mice].", "content": "7 human multiform glioblastoma have been transplanted into the brain of 100 new born Mice. Electron microscopy and chromosome analysis confirm the growth of a human tumor showing malignant features of glioblastoma.", "contents": "[Heterotransplantation of human glioblastoma in the brain of newborn mice]. 7 human multiform glioblastoma have been transplanted into the brain of 100 new born Mice. Electron microscopy and chromosome analysis confirm the growth of a human tumor showing malignant features of glioblastoma."}
{"id": "PMID:198160", "title": "[Comparative activity of endorphins on the opiate receptors].", "content": "Displacement of naloxone from membranes of Rat brain by alpha, beta and gamma-endorphins with and without Na+ in the incubating medium has been studied. beta-endorphin shows a higher affinity for the opiate receptors and a stronger agonist property than morphine. alpha and gamma-endorphins have a much lower affinity than morphine and a marked antagonist characteristic. This study suggests the possibility of naturally occurring antagonists of the opiate receptors.", "contents": "[Comparative activity of endorphins on the opiate receptors]. Displacement of naloxone from membranes of Rat brain by alpha, beta and gamma-endorphins with and without Na+ in the incubating medium has been studied. beta-endorphin shows a higher affinity for the opiate receptors and a stronger agonist property than morphine. alpha and gamma-endorphins have a much lower affinity than morphine and a marked antagonist characteristic. This study suggests the possibility of naturally occurring antagonists of the opiate receptors."}
{"id": "PMID:198161", "title": "Estrogens and experimental atherosclerosis in the baboon (Papio cynocephalus).", "content": "One hundred twenty-six adult female baboons (Papio cynocephalus) were hysterectomized and all except 18 were ovariectomized. The animals were fed a moderately atherogenic diet (40% calories form hydrogenated vegetable oil, 1.5 gm cholesterol/kcal) for two years. Ovariectomized-hysterectomized animals received estrone sulfate, ethynyl estradiol, or diethylstilbestrol orally in daily doses similar to those given humans. An ovariectomized-hysterectomized group and a hysterectomized group received no drug. The average total serum cholesterol concentration rose from 136 mg/dl to 223 mg/dl and declined to 186 mg/dl. Concentrations of cholesterol, triglyceride, and phospholipid in whole serum, low density lipoproteins and high density lipoproteins showed no consistent statistically significant differences among the groups. Triglyceride and phospholipid concentrations were higher in the estrogen-treated and intact-ovary groups than in the ovariectomized nonestrogen treated group, but not all pairwise comparisons were statistically significant. There were no consistent statistically significant differences in atherosclerotic lesions among the groups. Neither ovariectomy nor estrogen replacement influence diet-induced experimental atherosclerosis in the baboon within two years.", "contents": "Estrogens and experimental atherosclerosis in the baboon (Papio cynocephalus). One hundred twenty-six adult female baboons (Papio cynocephalus) were hysterectomized and all except 18 were ovariectomized. The animals were fed a moderately atherogenic diet (40% calories form hydrogenated vegetable oil, 1.5 gm cholesterol/kcal) for two years. Ovariectomized-hysterectomized animals received estrone sulfate, ethynyl estradiol, or diethylstilbestrol orally in daily doses similar to those given humans. An ovariectomized-hysterectomized group and a hysterectomized group received no drug. The average total serum cholesterol concentration rose from 136 mg/dl to 223 mg/dl and declined to 186 mg/dl. Concentrations of cholesterol, triglyceride, and phospholipid in whole serum, low density lipoproteins and high density lipoproteins showed no consistent statistically significant differences among the groups. Triglyceride and phospholipid concentrations were higher in the estrogen-treated and intact-ovary groups than in the ovariectomized nonestrogen treated group, but not all pairwise comparisons were statistically significant. There were no consistent statistically significant differences in atherosclerotic lesions among the groups. Neither ovariectomy nor estrogen replacement influence diet-induced experimental atherosclerosis in the baboon within two years."}
{"id": "PMID:198162", "title": "Breast carcinoma in children and adolescents.", "content": "Seventy-four cases of breast cancer in children and adolescents are reviewed. No predisposing factors were identified. A secretory type of mammary carcinoma characteristically seen in this age group has an excellent prognosis. Other types of mammary carcinoma which also occur in children may have a less favorable prognosis. Persistent breast masses in children and adolescents should be biopsied unless cystic, and should be treated as would carcinoma in adults, keeping in mind the favorable prognosis in so-called secretory carcinoma.", "contents": "Breast carcinoma in children and adolescents. Seventy-four cases of breast cancer in children and adolescents are reviewed. No predisposing factors were identified. A secretory type of mammary carcinoma characteristically seen in this age group has an excellent prognosis. Other types of mammary carcinoma which also occur in children may have a less favorable prognosis. Persistent breast masses in children and adolescents should be biopsied unless cystic, and should be treated as would carcinoma in adults, keeping in mind the favorable prognosis in so-called secretory carcinoma."}
{"id": "PMID:198163", "title": "Measurement of plasma lipoproteins by electrophoresis on polyacrylamide gel.", "content": "Results of densitometric analysis of lipoprotein peaks after electrophoresis on polyacrylamide gel and values obtained by the classical method of ultracentrifugation/precipitation correlate well. The correlation coefficients for high-density, low-density, and very-low-density lipoproteins are 0.85, 0.99, and 0.99, respectively. Thus the densitometric method for lipoprotein analysis appears to be suitable for routine clinical application.", "contents": "Measurement of plasma lipoproteins by electrophoresis on polyacrylamide gel. Results of densitometric analysis of lipoprotein peaks after electrophoresis on polyacrylamide gel and values obtained by the classical method of ultracentrifugation/precipitation correlate well. The correlation coefficients for high-density, low-density, and very-low-density lipoproteins are 0.85, 0.99, and 0.99, respectively. Thus the densitometric method for lipoprotein analysis appears to be suitable for routine clinical application."}
{"id": "PMID:198164", "title": "Creatine kinase in serum: 3. Further study of adenylate kinase inhibitors.", "content": "In search of an appropriate inhibitor to suppress the interference of adenylate kinase with the creatine kinase assay, we found that the combination diadenosine pentaphosphate (10 mumol/liter) and AMP (5 mmol/liter) is a better inhibitor than is fluoride (25 mmol/liter). The latter inhibits adenylate kinase uncompetitively and weakly (Ki = 2.5 mmol/liter), and must be incorporated in the starting reagent, and at 30 degrees C it becoms fully effective only after a lag phase of 6 min. In this concentration, fluoride inhibits adenylate kinase from erythrocytes, muscle, liver or platelets by 94, 92, 88, and 87%, respectively, and creatine kinase by 8%. Bromide and chloride also inhibit creatine kinase. Attempts to replace AMP by a specific inhibitor of liver adenylate kinase failed. Homologs of diadenosine pentaphosphate with either fewer or more phosphoryl groups in the polyphosphate bridge inhibited even more weakly than did the pentaphosphate. Platelets can significantly contribute to adenylate kinase activity in serum. The inhibitor combination inhibited adenylate kinase from platelets by 90%.", "contents": "Creatine kinase in serum: 3. Further study of adenylate kinase inhibitors. In search of an appropriate inhibitor to suppress the interference of adenylate kinase with the creatine kinase assay, we found that the combination diadenosine pentaphosphate (10 mumol/liter) and AMP (5 mmol/liter) is a better inhibitor than is fluoride (25 mmol/liter). The latter inhibits adenylate kinase uncompetitively and weakly (Ki = 2.5 mmol/liter), and must be incorporated in the starting reagent, and at 30 degrees C it becoms fully effective only after a lag phase of 6 min. In this concentration, fluoride inhibits adenylate kinase from erythrocytes, muscle, liver or platelets by 94, 92, 88, and 87%, respectively, and creatine kinase by 8%. Bromide and chloride also inhibit creatine kinase. Attempts to replace AMP by a specific inhibitor of liver adenylate kinase failed. Homologs of diadenosine pentaphosphate with either fewer or more phosphoryl groups in the polyphosphate bridge inhibited even more weakly than did the pentaphosphate. Platelets can significantly contribute to adenylate kinase activity in serum. The inhibitor combination inhibited adenylate kinase from platelets by 90%."}
{"id": "PMID:198165", "title": "Plasma lipoprotein changes in experimental cholestasis in the dog.", "content": "Plasma lipoproteins were compared before and after surgical induction of extrahepatic biliary obstruction in dogs by immunochemical techniques, zonal ultracentrifugation and gel filtration. A considerable increase in LDL was found one week after operation, with a zonal ultracentrifugal pattern which was more complex than that found before operation. The lipid composition was characterized by an increase of phospholipids and a decrease of triglycerides in cholestatic LDL fractions. None of the fractions displayed the inverse cholesterol-cholesterol ester ratio, characteristic for human LP-X. The apoprotein composition of cholestatic LDL was also markedly changed. Apoprotein A I, already present in the normal LDL2 subclass, increased and two apoproteins with apparent molecular weight of 35000-40000 appeared in considerable amounts. The amount of HDL was decreased during cholestasis without any appreciable changes in composition.", "contents": "Plasma lipoprotein changes in experimental cholestasis in the dog. Plasma lipoproteins were compared before and after surgical induction of extrahepatic biliary obstruction in dogs by immunochemical techniques, zonal ultracentrifugation and gel filtration. A considerable increase in LDL was found one week after operation, with a zonal ultracentrifugal pattern which was more complex than that found before operation. The lipid composition was characterized by an increase of phospholipids and a decrease of triglycerides in cholestatic LDL fractions. None of the fractions displayed the inverse cholesterol-cholesterol ester ratio, characteristic for human LP-X. The apoprotein composition of cholestatic LDL was also markedly changed. Apoprotein A I, already present in the normal LDL2 subclass, increased and two apoproteins with apparent molecular weight of 35000-40000 appeared in considerable amounts. The amount of HDL was decreased during cholestasis without any appreciable changes in composition."}
{"id": "PMID:198167", "title": "Alterations in serum prolactin heterogeneity by provocative tests in a patient with a pituitary tumour.", "content": "The proportion of serum prolactin heterogeneity were investigated in a patient with a pituitary adenoma producing both prolactin and growth hormone. Glucose tolerance (GTT) and insulin tolerance (ITT) tests were performed alone and in combination with chlorpromazine both before and after hypophysectomy. Serum prolactin multiple forms were separated by Sephadex G-100 column chromatography at 3 degrees C. None of the provocative tests altered the already elevated serum prolactin either before (300 ng/ml) or after (100 ng/ml)hypophysectomy. Chlorpromazine or ITT did not alter the proportion of prolactin heterogeneity; GTT, whether in conjunction with chlorpromazine or alone and both before and after hypophysectomy, increased the proportions of the larger molecular species. In five tests in which the GTT was not performed the prolactin heterogeneity was as follows: 'void volume', 4.9%; 'big', 13.1%; 'little', 82.1%; in those experiments in which the GTT was performed the proportions of prolactin heterogeneity were: 'void volume', 13.5%, 'big', 19.2%; 'little', 67.3%.", "contents": "Alterations in serum prolactin heterogeneity by provocative tests in a patient with a pituitary tumour. The proportion of serum prolactin heterogeneity were investigated in a patient with a pituitary adenoma producing both prolactin and growth hormone. Glucose tolerance (GTT) and insulin tolerance (ITT) tests were performed alone and in combination with chlorpromazine both before and after hypophysectomy. Serum prolactin multiple forms were separated by Sephadex G-100 column chromatography at 3 degrees C. None of the provocative tests altered the already elevated serum prolactin either before (300 ng/ml) or after (100 ng/ml)hypophysectomy. Chlorpromazine or ITT did not alter the proportion of prolactin heterogeneity; GTT, whether in conjunction with chlorpromazine or alone and both before and after hypophysectomy, increased the proportions of the larger molecular species. In five tests in which the GTT was not performed the prolactin heterogeneity was as follows: 'void volume', 4.9%; 'big', 13.1%; 'little', 82.1%; in those experiments in which the GTT was performed the proportions of prolactin heterogeneity were: 'void volume', 13.5%, 'big', 19.2%; 'little', 67.3%."}
{"id": "PMID:198168", "title": "Studies on the metabolic defect in Broad-beta disease (hyperlipoproteinaemia type III).", "content": "The apoprotein composition of the main lipoprotein fractions (VLDL, LDL-1, LDL-2 and HDL) was studied initially in 15 patients with Broad-beta disease. Analytical isoelectric focusing of urea-soluble apo-VLDL and apo LSL-1 demonstrated a variant pattern of the polymorphic Apoprotein E with a deficient Apo E-III band in all patients. The Apo E-III deficiency pattern was seen in only six out of 304 hyperlipidaemic controls. These six Apo E-III deficient controls had characteristic signs of Broad-beta disease, and thus represented patients not previously recognized as having the disorder. The Apo E focusing patterns were constant on repeated examinations and were stable under different metabolic conditions. The data show that Apo E-III deficiency in VLDL is a specific qualitative marker for Broad-beta disease, allowing an unequivocal diagnosis that had not been possible previously. Indirect evidence suggests that Apo E-III deficiency is the basic lipoprotein abnormality underlying the familial dyslipoproteinaemia.", "contents": "Studies on the metabolic defect in Broad-beta disease (hyperlipoproteinaemia type III). The apoprotein composition of the main lipoprotein fractions (VLDL, LDL-1, LDL-2 and HDL) was studied initially in 15 patients with Broad-beta disease. Analytical isoelectric focusing of urea-soluble apo-VLDL and apo LSL-1 demonstrated a variant pattern of the polymorphic Apoprotein E with a deficient Apo E-III band in all patients. The Apo E-III deficiency pattern was seen in only six out of 304 hyperlipidaemic controls. These six Apo E-III deficient controls had characteristic signs of Broad-beta disease, and thus represented patients not previously recognized as having the disorder. The Apo E focusing patterns were constant on repeated examinations and were stable under different metabolic conditions. The data show that Apo E-III deficiency in VLDL is a specific qualitative marker for Broad-beta disease, allowing an unequivocal diagnosis that had not been possible previously. Indirect evidence suggests that Apo E-III deficiency is the basic lipoprotein abnormality underlying the familial dyslipoproteinaemia."}
{"id": "PMID:198170", "title": "Species difference in the beta1/beta2-adrenoceptor selectivity of SM220CL in the cat and guinea-pig.", "content": "The beta-receptor stimulant effects of Sm220Cl, dl-N-(1,1-dimethyl-3-phenylpropyl)-2-hydroxy-2-(3,4-dihydroxy-2-methoxyphenyl)ethylamine, and (-)-isoprenaline have been compared in isolated atrial (beta1) and tracheal (beta2) preparations from guinea-pigs and cats. 2. The compounds were also tested for their ability to increase the heart rate (beta1), reduce serotonin-induced increases in pulmonary resistance (beta2), and decrease soleus muscle contractility (beta2) in vivo in the two species. 3. In all experiments cumulative concentration or dose-effect curves were established, EC50 or ED50 values obtained and molar activity-ratios (Sm220Cl: (-)-isoprenaline) calculated. 4. Calculated selectivity ratios [activity-ratio (heart):activity-ratio (bronchial smooth muscle)] from the in vitro experiments showed that Sm220Cl possessed beta2-receptor selectivity. This was more marked in guinea-pig than in cat preparations. 5. In the anaesthetized animals this species difference was more apparent; in cats Sm220Cl was non-selective in its actions for beta1- and beta2-receptor mediated responses, while marked beta2-receptor selectivity was obtained in the guinea-pig. 6. Since in both species the activity-ratios for beta2-receptor mediated actions are similar, the differences in the beta1/beta2-receptor selectivity of Sm220Cl are caused by the divergent cardiac effects produced by the drug.", "contents": "Species difference in the beta1/beta2-adrenoceptor selectivity of SM220CL in the cat and guinea-pig. The beta-receptor stimulant effects of Sm220Cl, dl-N-(1,1-dimethyl-3-phenylpropyl)-2-hydroxy-2-(3,4-dihydroxy-2-methoxyphenyl)ethylamine, and (-)-isoprenaline have been compared in isolated atrial (beta1) and tracheal (beta2) preparations from guinea-pigs and cats. 2. The compounds were also tested for their ability to increase the heart rate (beta1), reduce serotonin-induced increases in pulmonary resistance (beta2), and decrease soleus muscle contractility (beta2) in vivo in the two species. 3. In all experiments cumulative concentration or dose-effect curves were established, EC50 or ED50 values obtained and molar activity-ratios (Sm220Cl: (-)-isoprenaline) calculated. 4. Calculated selectivity ratios [activity-ratio (heart):activity-ratio (bronchial smooth muscle)] from the in vitro experiments showed that Sm220Cl possessed beta2-receptor selectivity. This was more marked in guinea-pig than in cat preparations. 5. In the anaesthetized animals this species difference was more apparent; in cats Sm220Cl was non-selective in its actions for beta1- and beta2-receptor mediated responses, while marked beta2-receptor selectivity was obtained in the guinea-pig. 6. Since in both species the activity-ratios for beta2-receptor mediated actions are similar, the differences in the beta1/beta2-receptor selectivity of Sm220Cl are caused by the divergent cardiac effects produced by the drug."}
{"id": "PMID:198179", "title": "Some myocardial factors of biological oxidation in experimental myocardial infarction.", "content": "In 175 dogs myocardial infarction was produced by high ligation of descending branch of left coronary artery. At various intervals after the intervention (1, 3, 5, 10, 30, 180 days), the activities and levels of NAD, NADH, FAD, riboflavin, cytochrome C, myoglobin, some NAD-dependent Krebs cycle enzymes, and mitochondrial succinate dehydrogenase and cytochrome oxidase were determined in the infarcted zone. It was found that in the infarcted zone there occurred substantial disturbances of various links constituting the tissue oxidative chain, in the stages of substrate dehydrogenation, electron transport to oxygen molecule, and myocardial oxygen uptake. The greatest disturbances took place in the systems of NAD and NAD-dependent enzymes, whereas the succinate oxidation system sustained substantially lesser damage. The decrease inlevels of flavonoids, which was likewise observed, participated also in the mechanism inhibiting succinate dehydrogenase. The cytochrome system activity was limited by the level of cytochrome C, whose deep decrease persisted considerably long in the infarcted zone. A certain role in disturbances of oxidative processes may have been played by the decreased concentration of myoglobin, an important myocardial reservoir of oxygen.", "contents": "Some myocardial factors of biological oxidation in experimental myocardial infarction. In 175 dogs myocardial infarction was produced by high ligation of descending branch of left coronary artery. At various intervals after the intervention (1, 3, 5, 10, 30, 180 days), the activities and levels of NAD, NADH, FAD, riboflavin, cytochrome C, myoglobin, some NAD-dependent Krebs cycle enzymes, and mitochondrial succinate dehydrogenase and cytochrome oxidase were determined in the infarcted zone. It was found that in the infarcted zone there occurred substantial disturbances of various links constituting the tissue oxidative chain, in the stages of substrate dehydrogenation, electron transport to oxygen molecule, and myocardial oxygen uptake. The greatest disturbances took place in the systems of NAD and NAD-dependent enzymes, whereas the succinate oxidation system sustained substantially lesser damage. The decrease inlevels of flavonoids, which was likewise observed, participated also in the mechanism inhibiting succinate dehydrogenase. The cytochrome system activity was limited by the level of cytochrome C, whose deep decrease persisted considerably long in the infarcted zone. A certain role in disturbances of oxidative processes may have been played by the decreased concentration of myoglobin, an important myocardial reservoir of oxygen."}
{"id": "PMID:198183", "title": "Actions of exogenous histones and other proteins on [3H]-thymidine incorporation into DNA of Novikoff hepatoma cells.", "content": "The effects of exogenous proteins on the incorporation of [3H]-thymidine into DNA was studied in Novikoff hepatoma ascites cells incubated in Eagle's minimal essential medium. A liver cytosol fraction (8 mg protein/ml) caused approximately 80% inhibition of isotope incorporation. The inhibitory activity of cytosol fractions from Morris hepatomas 9618A2, 5123C, and 20 were inversely related to their growth rate. Under conditions in which there appeared to be a density dependent inhibition of growth, a mean 10-20% stimulation of isotope incorporation was observed after addition of total calf thymus histones and individual fractions in the concentration range of 100-400 microgram/ml. In experiments with lower cell concentrations, a 60% or greater increase in [3H]-thymidine incorporation could be obtained with total calf thymus histone and with F1 and arginine-rich histones from rat liver. At concentrations of 1-2 mg/ml, histones inhibited DNA synthesis. Bovine serum albumin had little effect on DNA synthesis. Polylysine caused an 80-90% inhibition at a concentration of 1 mg/ml, but stimulatory effects were detected under certain conditions at 10 microgram/ml. The results suggest critical dependence on the ratio of cell and exogenous protein concentration in the action of proteins on DNA synthesis.", "contents": "Actions of exogenous histones and other proteins on [3H]-thymidine incorporation into DNA of Novikoff hepatoma cells. The effects of exogenous proteins on the incorporation of [3H]-thymidine into DNA was studied in Novikoff hepatoma ascites cells incubated in Eagle's minimal essential medium. A liver cytosol fraction (8 mg protein/ml) caused approximately 80% inhibition of isotope incorporation. The inhibitory activity of cytosol fractions from Morris hepatomas 9618A2, 5123C, and 20 were inversely related to their growth rate. Under conditions in which there appeared to be a density dependent inhibition of growth, a mean 10-20% stimulation of isotope incorporation was observed after addition of total calf thymus histones and individual fractions in the concentration range of 100-400 microgram/ml. In experiments with lower cell concentrations, a 60% or greater increase in [3H]-thymidine incorporation could be obtained with total calf thymus histone and with F1 and arginine-rich histones from rat liver. At concentrations of 1-2 mg/ml, histones inhibited DNA synthesis. Bovine serum albumin had little effect on DNA synthesis. Polylysine caused an 80-90% inhibition at a concentration of 1 mg/ml, but stimulatory effects were detected under certain conditions at 10 microgram/ml. The results suggest critical dependence on the ratio of cell and exogenous protein concentration in the action of proteins on DNA synthesis."}
{"id": "PMID:198184", "title": "Gene mapping in Mus musculus by interspecific cell hybridization: assignment of the genes for tripeptidase-1 to chromosome 10, dipeptidase-2 to chromosome 18, acid phosphatase-1 to chromosome 12, and adenylate kinase-1 to chromosome 2.", "content": "Chinese hamster X mouse somatic cell hybrids segregating mouse chromosomes were examined for their mouse chromosome content using trypsin-Giemsa (GTG) banding and Hoechst 33258 staining techniques. Simultaneously, they were scored for the presence of 24 mouse enzymes. The results confirm the assignments of 11 genes previously mapped by sexual genetics: Dip-1 and Id-1 to chromosome 1; Pgm-2 and Pgd to 4; Pgm-1 to 5; Gpi-1 to 7; Gr-1 to 8; Mpi-1 and Mod-1 to 9; Np-1 and Es-10 to 14. They also confirm chromosomally the assignments of 3 genes that were made by other somatic cell genetic studies: Aprt to 8; Hprt and alpha-gal to the X chromosome. But most importantly, four enzyme loci are assigned to four chromosomes that until now were not known to carry a biochemical marker which is expressed in cultured cells: Trip-1 to 10; Dip-2 to 18; Acp-1 to 12; and Ak-1 to 2. Cytogenetic examination of clones showing discordant segregation of HPRT and A-GAL, suggested the assignment of alpha-gal to region XE leads to XF of the mouse X chromosome. The cytologic studies provide a comparison between data from sexual genetics and somatic cell hybrids and validate hybrid cell techniques. They provide evidence of the reliability of scoring chromosomes by GTG and Hoechst staining and stress the importance of identifying clones with multiple chromosome rearrangements. Striking examples of norandom segregation of mouse chromosomes were observed in these hybrids with preferential retention of 15 and segregation of 11 and the Y chromosome.", "contents": "Gene mapping in Mus musculus by interspecific cell hybridization: assignment of the genes for tripeptidase-1 to chromosome 10, dipeptidase-2 to chromosome 18, acid phosphatase-1 to chromosome 12, and adenylate kinase-1 to chromosome 2. Chinese hamster X mouse somatic cell hybrids segregating mouse chromosomes were examined for their mouse chromosome content using trypsin-Giemsa (GTG) banding and Hoechst 33258 staining techniques. Simultaneously, they were scored for the presence of 24 mouse enzymes. The results confirm the assignments of 11 genes previously mapped by sexual genetics: Dip-1 and Id-1 to chromosome 1; Pgm-2 and Pgd to 4; Pgm-1 to 5; Gpi-1 to 7; Gr-1 to 8; Mpi-1 and Mod-1 to 9; Np-1 and Es-10 to 14. They also confirm chromosomally the assignments of 3 genes that were made by other somatic cell genetic studies: Aprt to 8; Hprt and alpha-gal to the X chromosome. But most importantly, four enzyme loci are assigned to four chromosomes that until now were not known to carry a biochemical marker which is expressed in cultured cells: Trip-1 to 10; Dip-2 to 18; Acp-1 to 12; and Ak-1 to 2. Cytogenetic examination of clones showing discordant segregation of HPRT and A-GAL, suggested the assignment of alpha-gal to region XE leads to XF of the mouse X chromosome. The cytologic studies provide a comparison between data from sexual genetics and somatic cell hybrids and validate hybrid cell techniques. They provide evidence of the reliability of scoring chromosomes by GTG and Hoechst staining and stress the importance of identifying clones with multiple chromosome rearrangements. Striking examples of norandom segregation of mouse chromosomes were observed in these hybrids with preferential retention of 15 and segregation of 11 and the Y chromosome."}
{"id": "PMID:198185", "title": "Dysrhythmias and sudden death in acromegalic heart disease. A clinicopathologic study.", "content": "A clinicopathologic investigation was carried out in a patient with acromegaly from acidophylic adenoma of the hypophysis. Pronounced cardiomegaly and disturbances in impulse formation and conduction led to sudden death. The problem of acromegalic cardiomyopathy has been reviewed. Particular attention has been focused on the histopathologic findings in the working and specific myocardium, and in the intrinsic nervous supply to the sinoatrial node, which were correlated with the electrocardiographic features of atrioventricular conduction delay and sick sinus syndrome.", "contents": "Dysrhythmias and sudden death in acromegalic heart disease. A clinicopathologic study. A clinicopathologic investigation was carried out in a patient with acromegaly from acidophylic adenoma of the hypophysis. Pronounced cardiomegaly and disturbances in impulse formation and conduction led to sudden death. The problem of acromegalic cardiomyopathy has been reviewed. Particular attention has been focused on the histopathologic findings in the working and specific myocardium, and in the intrinsic nervous supply to the sinoatrial node, which were correlated with the electrocardiographic features of atrioventricular conduction delay and sick sinus syndrome."}
{"id": "PMID:198186", "title": "Infectious mononucleosis and fatal myocarditis.", "content": "Mycocarditis is an uncommon manifestation and, very rarely, a lethal complication of infectious mononucleosis. A 14-year-old girl initially had exudative pharyngitis and splenomegaly and developed refractory ventricular fibrillation. The diagnosis of infectious mononucleosis was confirmed by both a strongly positive heterophil antibody test and a high titer of Epstein-Barr virus. Pathologic studies demonstrated extensive histiocytic and lypmhocytic infiltration of the myocardium.", "contents": "Infectious mononucleosis and fatal myocarditis. Mycocarditis is an uncommon manifestation and, very rarely, a lethal complication of infectious mononucleosis. A 14-year-old girl initially had exudative pharyngitis and splenomegaly and developed refractory ventricular fibrillation. The diagnosis of infectious mononucleosis was confirmed by both a strongly positive heterophil antibody test and a high titer of Epstein-Barr virus. Pathologic studies demonstrated extensive histiocytic and lypmhocytic infiltration of the myocardium."}
{"id": "PMID:198194", "title": "In vitro stimulation of thyroid ornithine decarboxylase activity and polyamines by thyrotropin.", "content": "Thyrotropin (TSH) stimulation of ornithine decarboxylase (ODC) activity and polyamine levels was studied in vitro in rat thyroids. The elevation in ODC activity was related to the concentration of TSH in the incubation medium with peak activity at a concentration of 25mU/ml. ODC activity with 50 mU/ml of TSH was 3 to 5-fold higher than control activity at 5 h of incubation; this stimulation was enhanced by the addition of 0.5 mM 3-isobutyl-l-methyl xanthine (MIX), a phosphodiesterase inhibitor. Dibutyryl cyclic AMP (DbcAMP) also stimulated ODC activity with a dose response up to 2.0 mm. The increase in ODC activity with TSH and MIX was prevented by incubation with actinomycin D (10 microgram/ml) or puromycin (0.2 mM). Putrescine concentrations in rat thyroids rose to three times basal levels after 6 h of incubation with TSH and MIX; no significant elevation in spermidine or spermine was observed after up to 7 h incubation. The increase in tissue putrescine preceded a rise in [3H]uridine incorporation into acid-soluble material that occurred at 7 h. The results suggest that stimulation of thyroid ODC activity by TSH is mediated by a cyclic AMP; the data further are consistent with a role for polyamines in the control of RNA synthesis in the thyroid.", "contents": "In vitro stimulation of thyroid ornithine decarboxylase activity and polyamines by thyrotropin. Thyrotropin (TSH) stimulation of ornithine decarboxylase (ODC) activity and polyamine levels was studied in vitro in rat thyroids. The elevation in ODC activity was related to the concentration of TSH in the incubation medium with peak activity at a concentration of 25mU/ml. ODC activity with 50 mU/ml of TSH was 3 to 5-fold higher than control activity at 5 h of incubation; this stimulation was enhanced by the addition of 0.5 mM 3-isobutyl-l-methyl xanthine (MIX), a phosphodiesterase inhibitor. Dibutyryl cyclic AMP (DbcAMP) also stimulated ODC activity with a dose response up to 2.0 mm. The increase in ODC activity with TSH and MIX was prevented by incubation with actinomycin D (10 microgram/ml) or puromycin (0.2 mM). Putrescine concentrations in rat thyroids rose to three times basal levels after 6 h of incubation with TSH and MIX; no significant elevation in spermidine or spermine was observed after up to 7 h incubation. The increase in tissue putrescine preceded a rise in [3H]uridine incorporation into acid-soluble material that occurred at 7 h. The results suggest that stimulation of thyroid ODC activity by TSH is mediated by a cyclic AMP; the data further are consistent with a role for polyamines in the control of RNA synthesis in the thyroid."}
{"id": "PMID:198195", "title": "Somatostatin inhibits urinary cyclic AMP excretion in diabetic rats.", "content": "Short term (30 min) infusion of cyclic somatostatin (50 microgram/rat), insulin (1 U/rat) or the two together significantly suppressed urinary cyclic AMP excretion in streptozotocin-diabetic rats. While somatostatin tended to increase cyclic GMP excretion, insulin had an opposite effect in diabetic but not in normal rats. It is suggested that somatostatin suppresses cyclic AMP excretion by inhibiting directly adenylate cyclase in liver and perhaps in other organs. The possibility that suppression of urinary cyclic AMP is due to inhibition of glucagon secretion is also considered.", "contents": "Somatostatin inhibits urinary cyclic AMP excretion in diabetic rats. Short term (30 min) infusion of cyclic somatostatin (50 microgram/rat), insulin (1 U/rat) or the two together significantly suppressed urinary cyclic AMP excretion in streptozotocin-diabetic rats. While somatostatin tended to increase cyclic GMP excretion, insulin had an opposite effect in diabetic but not in normal rats. It is suggested that somatostatin suppresses cyclic AMP excretion by inhibiting directly adenylate cyclase in liver and perhaps in other organs. The possibility that suppression of urinary cyclic AMP is due to inhibition of glucagon secretion is also considered."}
{"id": "PMID:198199", "title": "Perfusion of the pancreas isolated from pertussis-sensitized rats: potentiation of insulin secretory responses due to beta-adrenergic stimulation.", "content": "In order to study the mechanism by which pertussis-sensitized rats showed enhanced insulin secretory responses to various secretagogues (Sumi, T., and M. Ui, Endocrinology 97: 352, 1975), pancreases of rats receiving a single injection of Bordetella pertussis cells 3 days before were perfused with Krebs-Ringer solution, and release of insulin therefrom was compared with that from the pancreases of normal rats. Much more insulin was released from the pancreas of the pertussis-sensitized rat than from the pancreas of the normal rat in response to glucose, arginine, glibenclamide and 3-isobuty-l-methylxanthine. The inhibition of insulin secretion caused by epinephrine, norepinephrine or phenylephrine via alpha-adrenergic receptors in the pancreas of normal rats was no longer observable with the pancreas from pertussis-sensitized rats. Instead, the addition of epinephrine with or without phentolamine gave rise to a marked secretion of insulin from the pancreas of pertussis-sensitized rats which was prevented by propranolol. It is concluded that a single injection of B. pertussis into rats results in a sustained modification of insulin secretory processes in the pancreatic beta-cells in such a manner as to favor insulin secretory responses to beta-adrenergic stimulation and other secretagogues.", "contents": "Perfusion of the pancreas isolated from pertussis-sensitized rats: potentiation of insulin secretory responses due to beta-adrenergic stimulation. In order to study the mechanism by which pertussis-sensitized rats showed enhanced insulin secretory responses to various secretagogues (Sumi, T., and M. Ui, Endocrinology 97: 352, 1975), pancreases of rats receiving a single injection of Bordetella pertussis cells 3 days before were perfused with Krebs-Ringer solution, and release of insulin therefrom was compared with that from the pancreases of normal rats. Much more insulin was released from the pancreas of the pertussis-sensitized rat than from the pancreas of the normal rat in response to glucose, arginine, glibenclamide and 3-isobuty-l-methylxanthine. The inhibition of insulin secretion caused by epinephrine, norepinephrine or phenylephrine via alpha-adrenergic receptors in the pancreas of normal rats was no longer observable with the pancreas from pertussis-sensitized rats. Instead, the addition of epinephrine with or without phentolamine gave rise to a marked secretion of insulin from the pancreas of pertussis-sensitized rats which was prevented by propranolol. It is concluded that a single injection of B. pertussis into rats results in a sustained modification of insulin secretory processes in the pancreatic beta-cells in such a manner as to favor insulin secretory responses to beta-adrenergic stimulation and other secretagogues."}
{"id": "PMID:198201", "title": "Reduction in hepatic triiodothyronine binding capacity induced by fasting.", "content": "Triiodothyronine (T3) receptor kinetics were determined in liver nuclei isolated from fasting and fed rats. The results indicate that although affinity equilibrium constants (Ka) did not differ in the two groups, mean (+/- SE) maximal binding capacity (MBC) was reduced significantly to .30 +/- .05 nM/mg DNA in fasting compared to .46 +/- .07 nM/mg DNA (p less than .01) in the fed state. This observed decrease in MBC during fasting apparently could not be accounted for by a differential rates of loss of either DNA or of the receptor during the period of incubation.", "contents": "Reduction in hepatic triiodothyronine binding capacity induced by fasting. Triiodothyronine (T3) receptor kinetics were determined in liver nuclei isolated from fasting and fed rats. The results indicate that although affinity equilibrium constants (Ka) did not differ in the two groups, mean (+/- SE) maximal binding capacity (MBC) was reduced significantly to .30 +/- .05 nM/mg DNA in fasting compared to .46 +/- .07 nM/mg DNA (p less than .01) in the fed state. This observed decrease in MBC during fasting apparently could not be accounted for by a differential rates of loss of either DNA or of the receptor during the period of incubation."}
{"id": "PMID:198203", "title": "Effects of concurrent administration of lead, cadmium, and arsenic in the rat.", "content": "Humans are exposed to a number of toxic elements in the environment; however, most experiments with laboratory animals investigate only one toxic element. To determine if concomitant exposure to lead (Pb), cadmium (Cd), and/or arsenic (As) modified the changes produced by any one metal in various parameters of toxicity, 168 male, Sprague-Dawley, young adult rats were fed nutritionally adequate diets to which had been added 0 or 200 ppm Pb as Pb acetate, or 50 ppm Cd as Cd chloride, or 50 ppm As as sodium arsenate or arsanilic acid in a factorial design for a period of 10 weeks. At these concentrations, Cd and As reduced weight gain even when differences in food intake were taken into account; administration of both Cd and As depressed weight gain more than did either metal alone. Pb did not adversely affect food consumption or weight gain. Increased numbers of red blood cells (RBCs) were observed following administration of Pb, Cd, or As; usually more cells were observed when two or three metals were administered, compared to individual metals. Despite increasing numbers of circulating RBCs, hemoglobin and hematocrit were reduced, especially with the Pb-Cd combination and the Cd-arsanilic acid combination. Specific effects of Pb on heme synthesis were observed, including increased urinary excretion of delta-aminolevulinic acid; this increase was reduced by the presence of dietary cadmium. Analyses of blood showed values for the laboratory rat within normal ranges for blood urea nitrogen, creatinine, cholesterol, calcium, albumin, total protein, and bilirubin. Uric acid was increased by Pb, with little modification by dietary Cd or As content. Serum glutamate-oxalate transaminase activity was reduced by As. Serum alkaline phosphatase was greatly reduced by either As or Cd but not Pb. Combinations of As and Cd did not further reduce the activity of this enzyme. Kidney weight and kidney weight/body weight ratios were increased by Pb alone, with no effects of Cd or As alone or as interactions. Liver weight/body weight ratios were reduced in animals fed 50 ppm dietary Cd. Kidney histology shows predominantly Pb effects, namely, intranuclear inclusion bodies and cloudy swelling. Ultrastructural evaluation of kidneys from Pb-treated animals disclosed nuclear inclusion bodies of the usual morphology and mitochondrial swelling. Concurrent administration of Cd greatly minimized Pb effects on the kidney under conditions of this experiment. Liver histology suggests an increased rate of cell turnover with either As compound, but few specific changes.", "contents": "Effects of concurrent administration of lead, cadmium, and arsenic in the rat. Humans are exposed to a number of toxic elements in the environment; however, most experiments with laboratory animals investigate only one toxic element. To determine if concomitant exposure to lead (Pb), cadmium (Cd), and/or arsenic (As) modified the changes produced by any one metal in various parameters of toxicity, 168 male, Sprague-Dawley, young adult rats were fed nutritionally adequate diets to which had been added 0 or 200 ppm Pb as Pb acetate, or 50 ppm Cd as Cd chloride, or 50 ppm As as sodium arsenate or arsanilic acid in a factorial design for a period of 10 weeks. At these concentrations, Cd and As reduced weight gain even when differences in food intake were taken into account; administration of both Cd and As depressed weight gain more than did either metal alone. Pb did not adversely affect food consumption or weight gain. Increased numbers of red blood cells (RBCs) were observed following administration of Pb, Cd, or As; usually more cells were observed when two or three metals were administered, compared to individual metals. Despite increasing numbers of circulating RBCs, hemoglobin and hematocrit were reduced, especially with the Pb-Cd combination and the Cd-arsanilic acid combination. Specific effects of Pb on heme synthesis were observed, including increased urinary excretion of delta-aminolevulinic acid; this increase was reduced by the presence of dietary cadmium. Analyses of blood showed values for the laboratory rat within normal ranges for blood urea nitrogen, creatinine, cholesterol, calcium, albumin, total protein, and bilirubin. Uric acid was increased by Pb, with little modification by dietary Cd or As content. Serum glutamate-oxalate transaminase activity was reduced by As. Serum alkaline phosphatase was greatly reduced by either As or Cd but not Pb. Combinations of As and Cd did not further reduce the activity of this enzyme. Kidney weight and kidney weight/body weight ratios were increased by Pb alone, with no effects of Cd or As alone or as interactions. Liver weight/body weight ratios were reduced in animals fed 50 ppm dietary Cd. Kidney histology shows predominantly Pb effects, namely, intranuclear inclusion bodies and cloudy swelling. Ultrastructural evaluation of kidneys from Pb-treated animals disclosed nuclear inclusion bodies of the usual morphology and mitochondrial swelling. Concurrent administration of Cd greatly minimized Pb effects on the kidney under conditions of this experiment. Liver histology suggests an increased rate of cell turnover with either As compound, but few specific changes."}
{"id": "PMID:198204", "title": "Ultrastructural and biochemical effects of prolonged oral arsenic exposure on liver mitochondria of rats.", "content": "This investigation was undertaken to further delineate the subcellular manifestations of arsenic toxicity following chronic exposure using combined ultrastructural and biochemical techniques. Male rats were given access to deionized drinking water solutions containing 0, 20, 40, or 85 arsenic as arsenate (As(+5)) for 6 weeks. In situ swelling of liver mitochondria was the most prominent ultrastructural change observed. Mitochondrial respiration studies indicated decreased state 3 respiration and respiratory control ratios (RCR) for pyruvate/malate but not succinate mediated respiration. Specific activity of monoamine oxidase which is localized on the outer mitochondrial membrane showed increases of up to 150% of control and cytochrome-C oxidase which is localized on the inner mitochondrial membrane showed increases in specific activity of 150-200%. Activity of malate dehydrogenase which is localized in the mitochondrial matrix was unchanged at any dose level. These studies indicate that decreased mitochondrial respiration is only one aspect of arsenic toxicity to this organelle. Marked arsenic-mediated perturbation of important enzyme systems localized in mitochondria which participate in the control of respiration and other normal mitochondrial functions are also important manifestations of cellular dysfunction.", "contents": "Ultrastructural and biochemical effects of prolonged oral arsenic exposure on liver mitochondria of rats. This investigation was undertaken to further delineate the subcellular manifestations of arsenic toxicity following chronic exposure using combined ultrastructural and biochemical techniques. Male rats were given access to deionized drinking water solutions containing 0, 20, 40, or 85 arsenic as arsenate (As(+5)) for 6 weeks. In situ swelling of liver mitochondria was the most prominent ultrastructural change observed. Mitochondrial respiration studies indicated decreased state 3 respiration and respiratory control ratios (RCR) for pyruvate/malate but not succinate mediated respiration. Specific activity of monoamine oxidase which is localized on the outer mitochondrial membrane showed increases of up to 150% of control and cytochrome-C oxidase which is localized on the inner mitochondrial membrane showed increases in specific activity of 150-200%. Activity of malate dehydrogenase which is localized in the mitochondrial matrix was unchanged at any dose level. These studies indicate that decreased mitochondrial respiration is only one aspect of arsenic toxicity to this organelle. Marked arsenic-mediated perturbation of important enzyme systems localized in mitochondria which participate in the control of respiration and other normal mitochondrial functions are also important manifestations of cellular dysfunction."}
{"id": "PMID:198206", "title": "Hydrolysis and isomerization of trans,trans-farnesyl diphosphate by Andrographis tissue-culture enzymes.", "content": "Incubation of (3R,5S)-[5-3H1]mevalonate + (3RS)-[2-14C]mevalonate with Andrographis cell-free extract leads to trans,trans-farnesol and cis,trans-farnesol which both totally retain tritium. 2. This conflicts with our previous results which predict one third tritium loss in the cis,trans-farnesol. Inversion at C-1 during hydrolysis of trans,trans-farnesyl diphosphate to trans,trans-farnesol could explain this anomaly. 3. (1s)-trans,trans-[1-3H1]Farnesyl diphosphate and phosphate and (1R)-trans,trans-[1-3H1]-farnesyl diphosphate and phosphate, all prepared chemically, were hydrolysed with Andrographis phosphatase, and alkaline phosphatase and hydrogenolysed with lithium aluminium hydride and the product alcohols exchanged with liver alcohol hydrogenase. 4. Both Andrographis phosphatase and alkaline phosphatase hydrolyse trans,trans-farnesyl diphosphate and trans,trans-farnesyl phosphate with retention. 5. Hydrolysis of trans,trans-[1-18O]farnesyl diphosphate in H2(18O with both phosphatases supports P-O fission. 6. The C-1 configuration in (1S)-TRANS,TRANS-[1-3H1]farnesyl diphosphate and phosphate and (1R)-trans,trans-[1-3H1]farnesyl diphosphate and phosphate is progressively racemised in 0.01 M NH4OH/MeOH (1/9) AT - 20 degrees C.", "contents": "Hydrolysis and isomerization of trans,trans-farnesyl diphosphate by Andrographis tissue-culture enzymes. Incubation of (3R,5S)-[5-3H1]mevalonate + (3RS)-[2-14C]mevalonate with Andrographis cell-free extract leads to trans,trans-farnesol and cis,trans-farnesol which both totally retain tritium. 2. This conflicts with our previous results which predict one third tritium loss in the cis,trans-farnesol. Inversion at C-1 during hydrolysis of trans,trans-farnesyl diphosphate to trans,trans-farnesol could explain this anomaly. 3. (1s)-trans,trans-[1-3H1]Farnesyl diphosphate and phosphate and (1R)-trans,trans-[1-3H1]-farnesyl diphosphate and phosphate, all prepared chemically, were hydrolysed with Andrographis phosphatase, and alkaline phosphatase and hydrogenolysed with lithium aluminium hydride and the product alcohols exchanged with liver alcohol hydrogenase. 4. Both Andrographis phosphatase and alkaline phosphatase hydrolyse trans,trans-farnesyl diphosphate and trans,trans-farnesyl phosphate with retention. 5. Hydrolysis of trans,trans-[1-18O]farnesyl diphosphate in H2(18O with both phosphatases supports P-O fission. 6. The C-1 configuration in (1S)-TRANS,TRANS-[1-3H1]farnesyl diphosphate and phosphate and (1R)-trans,trans-[1-3H1]farnesyl diphosphate and phosphate is progressively racemised in 0.01 M NH4OH/MeOH (1/9) AT - 20 degrees C."}
{"id": "PMID:198205", "title": "Toxicological properties of lead.", "content": "The pathological effects of lead on the renal, nervous, reproductive, endocrine, and immune systems have been reviewed. Emphasis is placed on reported subclinical effects due to chronic, low-level lead exposure. The crucial issue of whether subtle behavioral, intellectual, and developmental impairment occurs in young children, as a result of lead-induced CNS damage is discussed in detail. This issue remains unresolved. Further studies are needed in order to determine the long-term health effects of continuous, low-level lead exposure.", "contents": "Toxicological properties of lead. The pathological effects of lead on the renal, nervous, reproductive, endocrine, and immune systems have been reviewed. Emphasis is placed on reported subclinical effects due to chronic, low-level lead exposure. The crucial issue of whether subtle behavioral, intellectual, and developmental impairment occurs in young children, as a result of lead-induced CNS damage is discussed in detail. This issue remains unresolved. Further studies are needed in order to determine the long-term health effects of continuous, low-level lead exposure."}
{"id": "PMID:198207", "title": "Dimerization of papain induced by mercuric chloride and a bifunctional organic mercurial.", "content": "The bifunctional mercurial meso-1,4-bis(acetatomercuri)-2,3-diethoxybutane and mercuric chloride are capable of dimerizing papain, by the attachment of the thiol group of two molecules of papain to each molecule of reagent. This is evident from the titration data, gel filtration and sedimentation equilibrium. The conformational change of papain necessary for this reaction is discussed.", "contents": "Dimerization of papain induced by mercuric chloride and a bifunctional organic mercurial. The bifunctional mercurial meso-1,4-bis(acetatomercuri)-2,3-diethoxybutane and mercuric chloride are capable of dimerizing papain, by the attachment of the thiol group of two molecules of papain to each molecule of reagent. This is evident from the titration data, gel filtration and sedimentation equilibrium. The conformational change of papain necessary for this reaction is discussed."}
{"id": "PMID:198208", "title": "Adenosine diphosphoribosylation of certain basic chromosomal proteins in isolated trout testis nuclei.", "content": "Isolated trout testis nuclei rapidly incorporate [alpha-32P]NAD+ into chromosomal proteins. Three proteins, very-lysine-rich histone (H1), a specific trout chromosomal protein (H6) and the sperm-specific protamines, incorporate the label as adenosine diphosphoribosyl (ADP-Rib) residues. No significant labeling of the nucleosomal 'core' histones H2A, H2B, H3 and H4 was observed. The linkage of the [32P](ADP-Rib) residues to each protein was very labile at pH values greater than 7.0 but by working at acidic pH and low temperatures the ADP-Rib label could be shown to be covalently bound to protein by gel electrophoresis and ion-exchange chromatography. The [32P]ADP-Rib chains could be removed by digestion with snake venom phosphodiesterase with the formation of AMP and phosphoribosyl-AMP.", "contents": "Adenosine diphosphoribosylation of certain basic chromosomal proteins in isolated trout testis nuclei. Isolated trout testis nuclei rapidly incorporate [alpha-32P]NAD+ into chromosomal proteins. Three proteins, very-lysine-rich histone (H1), a specific trout chromosomal protein (H6) and the sperm-specific protamines, incorporate the label as adenosine diphosphoribosyl (ADP-Rib) residues. No significant labeling of the nucleosomal 'core' histones H2A, H2B, H3 and H4 was observed. The linkage of the [32P](ADP-Rib) residues to each protein was very labile at pH values greater than 7.0 but by working at acidic pH and low temperatures the ADP-Rib label could be shown to be covalently bound to protein by gel electrophoresis and ion-exchange chromatography. The [32P]ADP-Rib chains could be removed by digestion with snake venom phosphodiesterase with the formation of AMP and phosphoribosyl-AMP."}
{"id": "PMID:198209", "title": "Reduction in beta-adrenergic response of cultured glioma cells following depletion of intracellular GTP.", "content": "1. When C6 glioma cells were incubated with mycophenolic acid, a potent and specific inhibitor of IMP:NAD oxidoreductase (EC 1.2.1.14) there was a marked depletion of the cellular content of GTP. The viability of the cells was unaffected. 2. The adenosine 3':5'-monophosphate (cyclic AMP) response of C6 glioma cells to the beta-adrenergic stimulant, (+/-)isoprenaline, was considerably reduced after treatment with mycophenolic acid. The diminished response to (+/-)isoprenaline was prevented by the inclusion of guanine in the culture medium along with mycophenolic acid. 3. The adenylate cyclase response to (+/-)isoprenaline of whole homogenates from C6 cells treated with mycophenolic acid was also depressed; the response was restored to normal by the addition of GTP. 4. The adenylate cyclase response to (+/-)isoprenaline of a membrane fraction prepared from homogenates of C6 cells was almost totally dependent on the presence of added GTP. Membrane fractions from control and mycophenolic-acid-treated C6 cells gave similar adenylate cyclase responses to (+/-)isoprenaline in the presence of GTP. 5. It is concluded that mycophenolic acid may depress the beta-adrenergic sensitivity of C6 cells by depleting the cellular content of GTP.", "contents": "Reduction in beta-adrenergic response of cultured glioma cells following depletion of intracellular GTP. 1. When C6 glioma cells were incubated with mycophenolic acid, a potent and specific inhibitor of IMP:NAD oxidoreductase (EC 1.2.1.14) there was a marked depletion of the cellular content of GTP. The viability of the cells was unaffected. 2. The adenosine 3':5'-monophosphate (cyclic AMP) response of C6 glioma cells to the beta-adrenergic stimulant, (+/-)isoprenaline, was considerably reduced after treatment with mycophenolic acid. The diminished response to (+/-)isoprenaline was prevented by the inclusion of guanine in the culture medium along with mycophenolic acid. 3. The adenylate cyclase response to (+/-)isoprenaline of whole homogenates from C6 cells treated with mycophenolic acid was also depressed; the response was restored to normal by the addition of GTP. 4. The adenylate cyclase response to (+/-)isoprenaline of a membrane fraction prepared from homogenates of C6 cells was almost totally dependent on the presence of added GTP. Membrane fractions from control and mycophenolic-acid-treated C6 cells gave similar adenylate cyclase responses to (+/-)isoprenaline in the presence of GTP. 5. It is concluded that mycophenolic acid may depress the beta-adrenergic sensitivity of C6 cells by depleting the cellular content of GTP."}
{"id": "PMID:198211", "title": "Purification of aldolase C from rat brain and hepatoma.", "content": "An isolation procedure for rat brain aldolase C has been developed which also permits the isolation of aldolase C from experimental hepatomas. Certain enzymatic properties (specific activity and Michaelis constant towards the two specific substrates: fructose 1,6-biphosphate and fructose 1-phosphate) and physico-chemical properties (molecular weight, N-terminal amino-acid) of the two enzymes have been studied and compared. Moreover, an amino-acid analysis has been carried out for rat brain aldolase C. Within experimental errors, the two enzymes appear to be identical.", "contents": "Purification of aldolase C from rat brain and hepatoma. An isolation procedure for rat brain aldolase C has been developed which also permits the isolation of aldolase C from experimental hepatomas. Certain enzymatic properties (specific activity and Michaelis constant towards the two specific substrates: fructose 1,6-biphosphate and fructose 1-phosphate) and physico-chemical properties (molecular weight, N-terminal amino-acid) of the two enzymes have been studied and compared. Moreover, an amino-acid analysis has been carried out for rat brain aldolase C. Within experimental errors, the two enzymes appear to be identical."}
{"id": "PMID:198212", "title": "Nuclear-magnetic-resonance studies of Pseudomonas aeruginosa cytochrome c-551.", "content": "Nuclear magnetic resonance (NMR) spectroscopy was used to study Pseudomonas aeruginosa cytochrome c-551. Assignments of resonances to specific residues have been made. A low-resolution X-ray structure was used to aid assignments. A structural comparison was made between P. aeruginosa cytochrome c-551 and mammalian cytochrome c, based on comparisons of NMR data.", "contents": "Nuclear-magnetic-resonance studies of Pseudomonas aeruginosa cytochrome c-551. Nuclear magnetic resonance (NMR) spectroscopy was used to study Pseudomonas aeruginosa cytochrome c-551. Assignments of resonances to specific residues have been made. A low-resolution X-ray structure was used to aid assignments. A structural comparison was made between P. aeruginosa cytochrome c-551 and mammalian cytochrome c, based on comparisons of NMR data."}
{"id": "PMID:198213", "title": "Ethanolaminosis. A newly recognized, generalized storage disease with cardiomegaly, cerebral dysfunction and early death.", "content": "A storage disease with cardiomegaly, generalized muscular hypotonia, cerebral dysfunction, failure to thrive and early death is described in two siblings. The first one died at the age of 10 months, the second at the age of 17 months. The symptoms were mainly due to lysosomal storage of a substance which had a positive reaction to PAS and Best's stain and which was resistant to diastase. This substance was stored in nearly all the organs, especially in the heart, liver, spleen and less in the brain and skeletal muscles. An increased renal excretion of ethanolamine, a greatly increased hepatic concentration of ethanolamine and diminished hepatic ethanolamine kinase activity could be demonstrated. Ethanolamine is essential for the synthesis of phospholipids. Both parents showed increased renal excretion of taurine. In several aspects, this syndrome is similar to the glycogenosis type II described by Pompe.", "contents": "Ethanolaminosis. A newly recognized, generalized storage disease with cardiomegaly, cerebral dysfunction and early death. A storage disease with cardiomegaly, generalized muscular hypotonia, cerebral dysfunction, failure to thrive and early death is described in two siblings. The first one died at the age of 10 months, the second at the age of 17 months. The symptoms were mainly due to lysosomal storage of a substance which had a positive reaction to PAS and Best's stain and which was resistant to diastase. This substance was stored in nearly all the organs, especially in the heart, liver, spleen and less in the brain and skeletal muscles. An increased renal excretion of ethanolamine, a greatly increased hepatic concentration of ethanolamine and diminished hepatic ethanolamine kinase activity could be demonstrated. Ethanolamine is essential for the synthesis of phospholipids. Both parents showed increased renal excretion of taurine. In several aspects, this syndrome is similar to the glycogenosis type II described by Pompe."}
{"id": "PMID:198216", "title": "Central cardiovascular effects of SQ 14,225, an angiotensin-converting enzyme inhibitor in chloralose-anesthetized cats.", "content": "Experiments were conducted in chloralose-anesthetized cats to investigate the central and peripheral cardiovascular effects of a new orally active angiotensin-converting inhibitor, SQ 14,225 (3-mercapto-2-D-methylpropanoyl-L-proline). I.v. administration of SQ 14,225 (0.31-3100 microgram/kg) antagonized the pressor responses to angiotensin I (AI) (310 ng/kg) i.v. in a dose-related manner but did not alter responses to angiotensin II (AII) (200 ng/kg) i.v. Similarly, intracerebroventricularly (i.c.v.) administered SQ 14,225 (0.31-310 microgram/kg perfused over 10 min) produced dose-related decreases in the centrally mediated pressor responses and heart increases elicited by AI (310 ng/kg) i.c.v. The central responses to AII (200 ng/kg) i.c.v. were not affected by SQ 14,225. Passage of SQ 14,225 out of the ventricular system into the systemic circulation was detected, but only at doses greater than that required to antagonize central AI responses. Doses of SQ 14,225 (310 microgram/kg and 3.1 mg/kg) i.v. which maximally inhibited i.v. AI responses, had no effect upon central AI activity. This finding suggests that passage of SQ 14,225 across the blood brain barrier into the central nervous system is restricted. Peripheral or central administration of SQ 14,225 produced only minimal transient decreases in blood pressure (less than 10 mm Hg). The results of these studies indicate that SQ 14,225 is a potent inhibitor of AI conversion in the brain as well as in the peripheral circulation.", "contents": "Central cardiovascular effects of SQ 14,225, an angiotensin-converting enzyme inhibitor in chloralose-anesthetized cats. Experiments were conducted in chloralose-anesthetized cats to investigate the central and peripheral cardiovascular effects of a new orally active angiotensin-converting inhibitor, SQ 14,225 (3-mercapto-2-D-methylpropanoyl-L-proline). I.v. administration of SQ 14,225 (0.31-3100 microgram/kg) antagonized the pressor responses to angiotensin I (AI) (310 ng/kg) i.v. in a dose-related manner but did not alter responses to angiotensin II (AII) (200 ng/kg) i.v. Similarly, intracerebroventricularly (i.c.v.) administered SQ 14,225 (0.31-310 microgram/kg perfused over 10 min) produced dose-related decreases in the centrally mediated pressor responses and heart increases elicited by AI (310 ng/kg) i.c.v. The central responses to AII (200 ng/kg) i.c.v. were not affected by SQ 14,225. Passage of SQ 14,225 out of the ventricular system into the systemic circulation was detected, but only at doses greater than that required to antagonize central AI responses. Doses of SQ 14,225 (310 microgram/kg and 3.1 mg/kg) i.v. which maximally inhibited i.v. AI responses, had no effect upon central AI activity. This finding suggests that passage of SQ 14,225 across the blood brain barrier into the central nervous system is restricted. Peripheral or central administration of SQ 14,225 produced only minimal transient decreases in blood pressure (less than 10 mm Hg). The results of these studies indicate that SQ 14,225 is a potent inhibitor of AI conversion in the brain as well as in the peripheral circulation."}
{"id": "PMID:198217", "title": "Failure of alpha-adrenergic stimulation by phenylephrine to enhance renin secretion in the isolated rat kidney.", "content": "The intrarenal effect of the alpha-receptor agonist phenylephrine on renin secretion was examined in the isolated rat kidney. Infusion of phenylephrine in non-vasoconstrictor doses resulted in secretion rates which were not significantly different from control values. Similarly no change in renin secretion was found when phenylephrine was infused at a dose that clearly caused renal vasoconstriction and increased vascular resistance. These results do not support the hypothesis of a role for the alpha-receptor in the stimulation of renin secretion by adrenergic activity.", "contents": "Failure of alpha-adrenergic stimulation by phenylephrine to enhance renin secretion in the isolated rat kidney. The intrarenal effect of the alpha-receptor agonist phenylephrine on renin secretion was examined in the isolated rat kidney. Infusion of phenylephrine in non-vasoconstrictor doses resulted in secretion rates which were not significantly different from control values. Similarly no change in renin secretion was found when phenylephrine was infused at a dose that clearly caused renal vasoconstriction and increased vascular resistance. These results do not support the hypothesis of a role for the alpha-receptor in the stimulation of renin secretion by adrenergic activity."}
{"id": "PMID:198218", "title": "Effect of phosphodiesterase inhibitors and dBcAMP on the inotropic and relaxing actions of histamine in cardiac muscle.", "content": "The influence of phosphodiesterase inhibitors, imidazole and dBcAMP on the action of histamine on peak tension, on rate of tension development and rate of relaxation of ventricular muscle of guinea pig's heart was investigated. It was found that theophylline plus dBcAMP enhanced the peak tension, (dF/dt)max and the rate of relaxation and increased the relaxing action of histamine. Imidazole, an activator of phosphodiesterase, also potentiated the action of histamine on peak tension, (dF/dt)max and rate of relaxation. Caffeine, a well-known inhibitor of phosphodiesterase, suppressed the relaxing action of histamine and epinephrine. These discrepant results could be explained by assuming the possibility that these drugs have effects other than those involving inhibition and activation of phosphodiesterase.", "contents": "Effect of phosphodiesterase inhibitors and dBcAMP on the inotropic and relaxing actions of histamine in cardiac muscle. The influence of phosphodiesterase inhibitors, imidazole and dBcAMP on the action of histamine on peak tension, on rate of tension development and rate of relaxation of ventricular muscle of guinea pig's heart was investigated. It was found that theophylline plus dBcAMP enhanced the peak tension, (dF/dt)max and the rate of relaxation and increased the relaxing action of histamine. Imidazole, an activator of phosphodiesterase, also potentiated the action of histamine on peak tension, (dF/dt)max and rate of relaxation. Caffeine, a well-known inhibitor of phosphodiesterase, suppressed the relaxing action of histamine and epinephrine. These discrepant results could be explained by assuming the possibility that these drugs have effects other than those involving inhibition and activation of phosphodiesterase."}
{"id": "PMID:198219", "title": "Elevation of adenosine 3',5'-monophosphate in the perfusate of rat kidney after addition of dopamine.", "content": "Dopamine (10-4 M) and vasopressin (1 mU/ml) were found to increase the level of cyclic AMP in the perfusate of rat kidney. There were some differences in the mode of action of these two drugs. Firstly, the effect of dopamine, but not of vasopressin, was completely antagonized by spiroperidol. Secondly, the maximal response was attained within 1 min after dopamine perfusion, but 8 min after vasopressin perfusion. These results suggest that a specific dopamine receptor which acts to increase the concentration of cyclic AMP is located in the vascular tissue of rat kidney.", "contents": "Elevation of adenosine 3',5'-monophosphate in the perfusate of rat kidney after addition of dopamine. Dopamine (10-4 M) and vasopressin (1 mU/ml) were found to increase the level of cyclic AMP in the perfusate of rat kidney. There were some differences in the mode of action of these two drugs. Firstly, the effect of dopamine, but not of vasopressin, was completely antagonized by spiroperidol. Secondly, the maximal response was attained within 1 min after dopamine perfusion, but 8 min after vasopressin perfusion. These results suggest that a specific dopamine receptor which acts to increase the concentration of cyclic AMP is located in the vascular tissue of rat kidney."}
{"id": "PMID:198220", "title": "Stress-induced ACTH release after removal of the hypothalamus in rats with atrophied neural lobe.", "content": "Twenty-four hours after isolation of the pituitary by surgical removal of the medial hypothalamus, i.e. in rats with pituitary island, E. coli endotoxin significantly increased the plasma corticosterone level. Atrophy of the neural lobe, due to pituitary stalk section performed one month prior to removal of the medial hypothalamus, did not prevent the increase of ACTH release by E. coli endotoxin. E. coli endotoxin-induced ACTH release in MBH-deprived animals does not appear to be a function of mechanisms operating only in the innervated lobe.", "contents": "Stress-induced ACTH release after removal of the hypothalamus in rats with atrophied neural lobe. Twenty-four hours after isolation of the pituitary by surgical removal of the medial hypothalamus, i.e. in rats with pituitary island, E. coli endotoxin significantly increased the plasma corticosterone level. Atrophy of the neural lobe, due to pituitary stalk section performed one month prior to removal of the medial hypothalamus, did not prevent the increase of ACTH release by E. coli endotoxin. E. coli endotoxin-induced ACTH release in MBH-deprived animals does not appear to be a function of mechanisms operating only in the innervated lobe."}
{"id": "PMID:198221", "title": "Site of action of 5-hydroxytryptophan and 5-hydroxytryptamine on the hypothalamo-pituitary-adrenal system in vitro.", "content": "5-hydroxytryptamine at a concentration of 0.04 microgram/ml was able to block the ACTH release caused by hypothalamic tissue (CRF) while it was ineffective when a hypothalamic extract containing CRF  was used. 5-hydroxytryptophan added to rat adrenal tissue caused a dose-dependent increase in corticosterone production. In a dose of 0.04 microgram/ml, 0.4 microgram/ml and 4.0 microgram/ml, 5-hydroxytryptophan was able to inhibit the ACTH release caused by hypothalamic tissue in vitro. However 0.04 microgram/ml was ineffective on the increase in ACTH secretion elicited by hypothalamic extract CRF. The data suggest that the inhibitory action of 5-hydroxytryptophan and 5-hydroxytryptamine is exerted at the hypothalamic level by inhibiting the release and/or synthesis of the corticotrophic releasing factor.", "contents": "Site of action of 5-hydroxytryptophan and 5-hydroxytryptamine on the hypothalamo-pituitary-adrenal system in vitro. 5-hydroxytryptamine at a concentration of 0.04 microgram/ml was able to block the ACTH release caused by hypothalamic tissue (CRF) while it was ineffective when a hypothalamic extract containing CRF  was used. 5-hydroxytryptophan added to rat adrenal tissue caused a dose-dependent increase in corticosterone production. In a dose of 0.04 microgram/ml, 0.4 microgram/ml and 4.0 microgram/ml, 5-hydroxytryptophan was able to inhibit the ACTH release caused by hypothalamic tissue in vitro. However 0.04 microgram/ml was ineffective on the increase in ACTH secretion elicited by hypothalamic extract CRF. The data suggest that the inhibitory action of 5-hydroxytryptophan and 5-hydroxytryptamine is exerted at the hypothalamic level by inhibiting the release and/or synthesis of the corticotrophic releasing factor."}
{"id": "PMID:198222", "title": "Persistence of Sendai virus in a mouse breeder colony and possibility to re-establish the virus free colonies.", "content": "An epizootic of Sendai virus infection occurred in a mouse breeder colony with respiratory signs, mortality, retarded growth in young and prolonged gestation period in adults. Thereafter, the infection persisted in this colony without any clinical signs and with 90 to 100% antibody positivity in adults. Weanlings had maternal antibodies and no pneumonic lesions. Antibodies were hardly detected in 6-week-old mice with high incidence of red hepatization or congestion in their lungs, but mice over 8 weeks of age had antibody without the lesions. After isolating weanlings and pregnant mice with antibodies from the infected colony, the isolated weanlings and offspring from the isolated dams became negative for Sendai virus antibodies.", "contents": "Persistence of Sendai virus in a mouse breeder colony and possibility to re-establish the virus free colonies. An epizootic of Sendai virus infection occurred in a mouse breeder colony with respiratory signs, mortality, retarded growth in young and prolonged gestation period in adults. Thereafter, the infection persisted in this colony without any clinical signs and with 90 to 100% antibody positivity in adults. Weanlings had maternal antibodies and no pneumonic lesions. Antibodies were hardly detected in 6-week-old mice with high incidence of red hepatization or congestion in their lungs, but mice over 8 weeks of age had antibody without the lesions. After isolating weanlings and pregnant mice with antibodies from the infected colony, the isolated weanlings and offspring from the isolated dams became negative for Sendai virus antibodies."}
{"id": "PMID:198233", "title": "Biologic effects of orally administered deuterium oxide on rat liver.", "content": "Rats were made to drink D2O mixed water (30: 70) for 6 weeks in order to study the biological effects of orally administered D2O on the liver. Heavy water administration results in gradual decrease in the body weight whereas the liver showed marginal increase in weight throughout the experimental period. Phosphatases and dehydrogenases were analyzed biochemically. Acid phosphatase, glucose-6-phosphatase and adenosine triphosphatase registered fall in contrast to alkaline phosphatase, SDH and LDH, all of which showed a definite increase. Lipids, nucleic acids and proteins, estimated biochemically, gradually decreased throughout the experimental period in response to D2O feeding.", "contents": "Biologic effects of orally administered deuterium oxide on rat liver. Rats were made to drink D2O mixed water (30: 70) for 6 weeks in order to study the biological effects of orally administered D2O on the liver. Heavy water administration results in gradual decrease in the body weight whereas the liver showed marginal increase in weight throughout the experimental period. Phosphatases and dehydrogenases were analyzed biochemically. Acid phosphatase, glucose-6-phosphatase and adenosine triphosphatase registered fall in contrast to alkaline phosphatase, SDH and LDH, all of which showed a definite increase. Lipids, nucleic acids and proteins, estimated biochemically, gradually decreased throughout the experimental period in response to D2O feeding."}
{"id": "PMID:198236", "title": "Non-synaptic chemical neurotransmission.", "content": "Images with apparently gemmulofugal polarity in the EPL of the olfactory bulb are the result of sectioning, along misleading planes, gemmulopetal synapses containing postsynaptic vesicles. Unless one accepts a bidirectional conduction for chemical synapses, the internal granule cells lack actual gemmulofugal synapses and the neurotransmitter contained on their vesicles must act at non-synaptic membranes.", "contents": "Non-synaptic chemical neurotransmission. Images with apparently gemmulofugal polarity in the EPL of the olfactory bulb are the result of sectioning, along misleading planes, gemmulopetal synapses containing postsynaptic vesicles. Unless one accepts a bidirectional conduction for chemical synapses, the internal granule cells lack actual gemmulofugal synapses and the neurotransmitter contained on their vesicles must act at non-synaptic membranes."}
{"id": "PMID:198247", "title": "In vitro effects of eledoisin on amylase secretion and cyclic AMP concentration of rat's parotids.", "content": "Amylase secretion from in vitro rat parotids was strongly stimulated by eledoisin. In the same experimental conditions the glandular cAMP concentration was not affected by the peptide. The results might indicate that the effect of eledoisin on rat parotids is not mediated by cAMP.", "contents": "In vitro effects of eledoisin on amylase secretion and cyclic AMP concentration of rat's parotids. Amylase secretion from in vitro rat parotids was strongly stimulated by eledoisin. In the same experimental conditions the glandular cAMP concentration was not affected by the peptide. The results might indicate that the effect of eledoisin on rat parotids is not mediated by cAMP."}
{"id": "PMID:198244", "title": "[Role of alpha- and beta-adrenoreceptors in catecholamine regulation of the natriuretic function of the kidneys in rats].", "content": "In acute tests set up on rats subject to investigations was the significance of alpha- and beta-adrenoreceptors in the mechanism of the catecholamines influence on the natriuretic function of the rats' kidneys. Phentolamine did not obstruct the stimulating action of epinephrine on the tubular reabsorption of sodium, but perverted its inhibitory effect on the glomerular filtration. Inderal did not affect the glomerular action of epinephrine, but fully prevented its effect on reabsorption of sodium in the tubules of the kidney. When used in a dose failing to produce any significant changes in the systemic arterial pressure isopropylnorepinephrine increased glomerular filtration, but inhibited excretion of sodium, augmenting its tubular reabsorption. The resulting implication is that alpha-adrenoreceptors participate in the mechanism of the catecholamines regulation of the intrarenal hemodynamics, whereas beta-adrenoreceptors play the part of mediating their activating influence on the tubular transport of sodium.", "contents": "[Role of alpha- and beta-adrenoreceptors in catecholamine regulation of the natriuretic function of the kidneys in rats]. In acute tests set up on rats subject to investigations was the significance of alpha- and beta-adrenoreceptors in the mechanism of the catecholamines influence on the natriuretic function of the rats' kidneys. Phentolamine did not obstruct the stimulating action of epinephrine on the tubular reabsorption of sodium, but perverted its inhibitory effect on the glomerular filtration. Inderal did not affect the glomerular action of epinephrine, but fully prevented its effect on reabsorption of sodium in the tubules of the kidney. When used in a dose failing to produce any significant changes in the systemic arterial pressure isopropylnorepinephrine increased glomerular filtration, but inhibited excretion of sodium, augmenting its tubular reabsorption. The resulting implication is that alpha-adrenoreceptors participate in the mechanism of the catecholamines regulation of the intrarenal hemodynamics, whereas beta-adrenoreceptors play the part of mediating their activating influence on the tubular transport of sodium."}
{"id": "PMID:198245", "title": "[Effect of non-steroid anti-inflammatory agents on components of the kinin system in animals with experimental inflammation].", "content": "The influence exerted by a number of non-steroid antiphlogistic agents on the fermentative mechanism responsible for the formation and decomposition of kininines in an inflammation focus and on the permeability of vessels in a skin changed under the effect of exogenous bradykininine was studied. Bradykininine, chigamin, sodium salicylate and mephenaminate are shown to inhibit \"in vitro\" the kininogenic and intensify the kininase activity of the exudate in rats with turpentine-induced pleuritis, while indometacin affects only the activity of kininogenases. Butadion, chingamin and sodium mephenaminate merely reduce the reactivity of the skin with respect to exogenous bradykininine.", "contents": "[Effect of non-steroid anti-inflammatory agents on components of the kinin system in animals with experimental inflammation]. The influence exerted by a number of non-steroid antiphlogistic agents on the fermentative mechanism responsible for the formation and decomposition of kininines in an inflammation focus and on the permeability of vessels in a skin changed under the effect of exogenous bradykininine was studied. Bradykininine, chigamin, sodium salicylate and mephenaminate are shown to inhibit \"in vitro\" the kininogenic and intensify the kininase activity of the exudate in rats with turpentine-induced pleuritis, while indometacin affects only the activity of kininogenases. Butadion, chingamin and sodium mephenaminate merely reduce the reactivity of the skin with respect to exogenous bradykininine."}
{"id": "PMID:198254", "title": "Virus-specific RNA in selected cell lines derived from RSV-induced tumour.", "content": "The presence of virus-specific RNA in mammalian tumour cell lines of RSV aetiology was studied using molecular hybridization between the PR-RSV 3H-DNA probe synthetized by the endogenous RNA-directed DNA polymerase reaction and cellular RNA. It was found that both virogenic XC cells harbouring the full PR-RSV genome and cryptovirogenic RVP3 cells harbouring an incomplete PR-RSV genome contain virus-specific RNA. The degree of homology between such RNA and PR-RSV 3H-DNA probe reached 10--12% in XC cells and 28--30% in RVP3 cells. It was found that RVP3 cells contain larger amounts of virus-specific RNA than XC cells and that it is localized in the gradient zone corresponding to 20--25S.", "contents": "Virus-specific RNA in selected cell lines derived from RSV-induced tumour. The presence of virus-specific RNA in mammalian tumour cell lines of RSV aetiology was studied using molecular hybridization between the PR-RSV 3H-DNA probe synthetized by the endogenous RNA-directed DNA polymerase reaction and cellular RNA. It was found that both virogenic XC cells harbouring the full PR-RSV genome and cryptovirogenic RVP3 cells harbouring an incomplete PR-RSV genome contain virus-specific RNA. The degree of homology between such RNA and PR-RSV 3H-DNA probe reached 10--12% in XC cells and 28--30% in RVP3 cells. It was found that RVP3 cells contain larger amounts of virus-specific RNA than XC cells and that it is localized in the gradient zone corresponding to 20--25S."}
{"id": "PMID:198256", "title": "Histopathology of carcinomas of the liver in mice ingesting heptachlor or heptachlor epoxide.", "content": "C3H male and female mice, ingesting 10 ppm of the pesticides heptachlor or heptachlor epoxide in the diet, developed highly significant incidences of carcinomas of the liver. The carcinomas varied from well-differentiated to poorly differentiated and undifferentiated and were capable of invasion and metastasis.", "contents": "Histopathology of carcinomas of the liver in mice ingesting heptachlor or heptachlor epoxide. C3H male and female mice, ingesting 10 ppm of the pesticides heptachlor or heptachlor epoxide in the diet, developed highly significant incidences of carcinomas of the liver. The carcinomas varied from well-differentiated to poorly differentiated and undifferentiated and were capable of invasion and metastasis."}
{"id": "PMID:198257", "title": "Differential cytology of breast cancer.", "content": "The aim of the study was to investigate the possibility of predicting the histologic type of different breast cancers by semi-quantitative screening of cytologic criteria. Cytologic material was obtained by the aspiration technique. The frequency of ten cytologic criteria was correlated to five histologic types of breast cancer. Hitherto, it has not been possible to define histologic types of breast carcinomas on the basis of cytologic criteria alone. While the occurrence of cellularity, intercellular cohesion, foam cells and necroses often varies from slide to slide within one particular carcinoma, other features such as nuclear diameter, polymorphism, anisonucleosis, apocrine carcinoma cells, and enlarged nucleoli are more or less uniformly distributed. The application of these cytologic criteria thus uniformly represented in a tumour may prove to be a more reliable method for classifying breast carcinomas than the use of histologic growth patterns which are often inhomogenous within each individual neoplasm.", "contents": "Differential cytology of breast cancer. The aim of the study was to investigate the possibility of predicting the histologic type of different breast cancers by semi-quantitative screening of cytologic criteria. Cytologic material was obtained by the aspiration technique. The frequency of ten cytologic criteria was correlated to five histologic types of breast cancer. Hitherto, it has not been possible to define histologic types of breast carcinomas on the basis of cytologic criteria alone. While the occurrence of cellularity, intercellular cohesion, foam cells and necroses often varies from slide to slide within one particular carcinoma, other features such as nuclear diameter, polymorphism, anisonucleosis, apocrine carcinoma cells, and enlarged nucleoli are more or less uniformly distributed. The application of these cytologic criteria thus uniformly represented in a tumour may prove to be a more reliable method for classifying breast carcinomas than the use of histologic growth patterns which are often inhomogenous within each individual neoplasm."}
{"id": "PMID:198275", "title": "A review of the current status of oil adjuvants in foot--and--mouth disease vaccines.", "content": "Review of lipovaccines since 1916, including oil adjuvants (1935-1943) and the two Freund's adjuvants. The first oil-adjuvanted vaccines appeared in 1961. Criticism of the water-in-oil and oil-in-water vaccines and description of the mineral oil adjuvants which are available today. The authors set forth the advantages of oil adjuvants and secondary reactions which might occur; they are particularly interested in the foot-and-mouth disease vaccine intended for use in swine and express their regret that no method of standardization has yet been adopted for oil-adjuvanted vaccines which are promising but which necessitate still further study.", "contents": "A review of the current status of oil adjuvants in foot--and--mouth disease vaccines. Review of lipovaccines since 1916, including oil adjuvants (1935-1943) and the two Freund's adjuvants. The first oil-adjuvanted vaccines appeared in 1961. Criticism of the water-in-oil and oil-in-water vaccines and description of the mineral oil adjuvants which are available today. The authors set forth the advantages of oil adjuvants and secondary reactions which might occur; they are particularly interested in the foot-and-mouth disease vaccine intended for use in swine and express their regret that no method of standardization has yet been adopted for oil-adjuvanted vaccines which are promising but which necessitate still further study."}
{"id": "PMID:198276", "title": "Efficiency testing of foot--and--mouth disease vaccines prepared from strain \"C\" with different adjuvants.", "content": "Various oil adjuvants were tested for immunogenicity enhancing action in \"C\" type FMD monovaccine preparations. The following composition proved to be optimal in mouse tests: Bayl F 85%, Arlacel A 14% Tween 80 1%. As to the quantitative relations of antigen adjuvant, 40% oil to 60% antigen was the best among all proportions tested. Oil-adjuvanted vaccines failed to evoke an immune response in calves, but proved to be the preparation of choice for adult cattle. Oil containing and DEAE-dextran-containing vaccines had an equal efficiency in pigs; both conferred full protection on one in three pigs treated with 2.5-fold bovine doses. The number of vaccinated pigs was too small to permit definitive conclusions, but it seems clear that only oil dextran are efficient adjuvants of FMD vaccines for pigs, and that the antigen component of such vaccines should be increased considerably in order to obtain a greater potency.", "contents": "Efficiency testing of foot--and--mouth disease vaccines prepared from strain \"C\" with different adjuvants. Various oil adjuvants were tested for immunogenicity enhancing action in \"C\" type FMD monovaccine preparations. The following composition proved to be optimal in mouse tests: Bayl F 85%, Arlacel A 14% Tween 80 1%. As to the quantitative relations of antigen adjuvant, 40% oil to 60% antigen was the best among all proportions tested. Oil-adjuvanted vaccines failed to evoke an immune response in calves, but proved to be the preparation of choice for adult cattle. Oil containing and DEAE-dextran-containing vaccines had an equal efficiency in pigs; both conferred full protection on one in three pigs treated with 2.5-fold bovine doses. The number of vaccinated pigs was too small to permit definitive conclusions, but it seems clear that only oil dextran are efficient adjuvants of FMD vaccines for pigs, and that the antigen component of such vaccines should be increased considerably in order to obtain a greater potency."}
{"id": "PMID:198277", "title": "[Use of anti-foot-and-mouth disease vaccine in oil adjuvant in young cattle].", "content": "A comparative study of the activity of foot-and-mouth disease vaccines, both aqueous- and oil-adjuvanted, was carried out on young bovines from vaccinated mothers. The immunity of these animals against foot-and-mouth disease was controlled after the first vaccination and booster by serology (neutralizing antibody count and immunology virulence testing). After having followed the kinetics of decrease in seroneutralizing antibodies of maternal origin the animals were vaccinated at the age of 11 weeks either with aqueous-adjuvanted or oil-adjuvanted vaccine. A booster dose was given two months later. Blood samples were taken at regular intervals and two virulence tests were made, one 21 days after the first vaccination and the other six months after the booster dose.", "contents": "[Use of anti-foot-and-mouth disease vaccine in oil adjuvant in young cattle]. A comparative study of the activity of foot-and-mouth disease vaccines, both aqueous- and oil-adjuvanted, was carried out on young bovines from vaccinated mothers. The immunity of these animals against foot-and-mouth disease was controlled after the first vaccination and booster by serology (neutralizing antibody count and immunology virulence testing). After having followed the kinetics of decrease in seroneutralizing antibodies of maternal origin the animals were vaccinated at the age of 11 weeks either with aqueous-adjuvanted or oil-adjuvanted vaccine. A booster dose was given two months later. Blood samples were taken at regular intervals and two virulence tests were made, one 21 days after the first vaccination and the other six months after the booster dose."}
{"id": "PMID:198280", "title": "[Production, control and use in swine of anti-foot-and-mouth disease vaccine in oil adjuvant].", "content": "A certain number of parameters involved in the manufacture, control and use of an efficacious vaccine against foot-and-mouth disease have been studied. This report considers the problems raised by the standardization of the raw material constituent to the vaccine as well as the different types of innocuity and activity testing carried out on sows, young pigs and bacon pigs. Special attention is given to virulence testing methods, to the criteria allowing evaluation of the quality of the vaccines and to the transmission of maternal immunity of the sows to their piglets and its incidence on the vaccination schedule.", "contents": "[Production, control and use in swine of anti-foot-and-mouth disease vaccine in oil adjuvant]. A certain number of parameters involved in the manufacture, control and use of an efficacious vaccine against foot-and-mouth disease have been studied. This report considers the problems raised by the standardization of the raw material constituent to the vaccine as well as the different types of innocuity and activity testing carried out on sows, young pigs and bacon pigs. Special attention is given to virulence testing methods, to the criteria allowing evaluation of the quality of the vaccines and to the transmission of maternal immunity of the sows to their piglets and its incidence on the vaccination schedule."}
{"id": "PMID:198281", "title": "[Comparison of a bivalent anti-foot-and-mouth disease vaccine with oil adjuvant to a vaccine with DEAE-dextran adjuvant in swine].", "content": "The report compares the compatibility, efficacity and serology response of two bivalent anti-foot-and-mouth disease vaccines (OC). One is oil-adjuvanted and the other based on diethyl-amino-ethyl-dextran (DEAE-Dextran). After vaccination no general clinical or local reactions are normally observed. Tissular reactions at the inoculation site are more severe with the oil-adjuvanted vaccine than with the DEAE-Dextran vaccine. Meat inspection, about three months after injection of the vaccine, showed the lesions to be in regression and negligible. The control of activity has been performed by the virulence test. For the oil-adjuvanted vaccine, protection against O1-Lausanne, 5, 21 and 90 days after vaccination is 90%, 80-100% and 55% respectively. For the DEAE-Dextran vaccine, these levels of protection are 80% after 5 days and 20-70% after 21 days. The percentage of swine protected against C-Noville 35 days after vaccination is 100% for the oil-adjuvanted vaccine and 70% for the DEAE-Dextran vaccine. The evolution of the amount of serum antibodies was followed for three months by the method of seroneutralization on cell cultures.", "contents": "[Comparison of a bivalent anti-foot-and-mouth disease vaccine with oil adjuvant to a vaccine with DEAE-dextran adjuvant in swine]. The report compares the compatibility, efficacity and serology response of two bivalent anti-foot-and-mouth disease vaccines (OC). One is oil-adjuvanted and the other based on diethyl-amino-ethyl-dextran (DEAE-Dextran). After vaccination no general clinical or local reactions are normally observed. Tissular reactions at the inoculation site are more severe with the oil-adjuvanted vaccine than with the DEAE-Dextran vaccine. Meat inspection, about three months after injection of the vaccine, showed the lesions to be in regression and negligible. The control of activity has been performed by the virulence test. For the oil-adjuvanted vaccine, protection against O1-Lausanne, 5, 21 and 90 days after vaccination is 90%, 80-100% and 55% respectively. For the DEAE-Dextran vaccine, these levels of protection are 80% after 5 days and 20-70% after 21 days. The percentage of swine protected against C-Noville 35 days after vaccination is 100% for the oil-adjuvanted vaccine and 70% for the DEAE-Dextran vaccine. The evolution of the amount of serum antibodies was followed for three months by the method of seroneutralization on cell cultures."}
{"id": "PMID:198284", "title": "Data on a FMD virus of type \"A\" isolated in Italy in 1975.", "content": "A strain of FMD virus type A was isolated in a disease outbreak in Alessandria, Italy, in December 1975. Affected animals were young unvaccinated bovines and pigs of a very restricted region. No further spread has been observed. The strain was compared with some subtype strains of type A, including the Italian vaccinal strain. This Italy 1975 strain differs from all the other viruses included in the performed tests.", "contents": "Data on a FMD virus of type \"A\" isolated in Italy in 1975. A strain of FMD virus type A was isolated in a disease outbreak in Alessandria, Italy, in December 1975. Affected animals were young unvaccinated bovines and pigs of a very restricted region. No further spread has been observed. The strain was compared with some subtype strains of type A, including the Italian vaccinal strain. This Italy 1975 strain differs from all the other viruses included in the performed tests."}
{"id": "PMID:198285", "title": "[Serological study of several strains of foot-and-mouth disease virus type \"O\" isolated in Europe between 1971 and 1975: application of the biomathematical system of classification].", "content": "Nine strains of foot-and-mouth disease virus type \"O\" received in our laboratories since 1971 have been studied serologically by Osler's quantitative method of complement fixation (50% hemolysis). The results, submitted to the biomathematical system of bidimensional classification, allow to conclude that at present in Europe there are two groups of foot-and-mouth disease strains of type \"O\"; one has reference to our vaccinal strain \"O Lausanne 1965\" and the other to \"O Romania 1972\" strain, which has certain points of similarity with subtype \"O2\". In addition, strain \"O Hungary 1975\" has been studied on bovines; the immunological tests confirm the serological test.", "contents": "[Serological study of several strains of foot-and-mouth disease virus type \"O\" isolated in Europe between 1971 and 1975: application of the biomathematical system of classification]. Nine strains of foot-and-mouth disease virus type \"O\" received in our laboratories since 1971 have been studied serologically by Osler's quantitative method of complement fixation (50% hemolysis). The results, submitted to the biomathematical system of bidimensional classification, allow to conclude that at present in Europe there are two groups of foot-and-mouth disease strains of type \"O\"; one has reference to our vaccinal strain \"O Lausanne 1965\" and the other to \"O Romania 1972\" strain, which has certain points of similarity with subtype \"O2\". In addition, strain \"O Hungary 1975\" has been studied on bovines; the immunological tests confirm the serological test."}
{"id": "PMID:198286", "title": "Examination of differences between foot-and-mouth disease virus strains using a radioimmunoassay techinque.", "content": "A radioimmunoassay (RIA) technique was used to compare different samples of type SAT 2 foot-and-mouth disease (FMD) viruses. The reaction involved the measurement of the competition of heterologous virus with homologous virus for previously titrated homologous antiserum. The results showed that differences occurred between the viruses examined. Viruses could be grouped according to their ability to compete with the homologous virus, and statistically significant differences between virus 'groups' were observed. A comparison of the relationships between the viruses using RIA and complement fixation tests was made. The results did not always correlate. Certain homologous antigen/antibody combinations were more discriminating. The method might prove useful in the examination of a large number of field strain viruses using a well-characterized vaccine virus homologous system, particularly if the method is adapted to use antisera specific for the neutralizing antigen of the homologous test virus.", "contents": "Examination of differences between foot-and-mouth disease virus strains using a radioimmunoassay techinque. A radioimmunoassay (RIA) technique was used to compare different samples of type SAT 2 foot-and-mouth disease (FMD) viruses. The reaction involved the measurement of the competition of heterologous virus with homologous virus for previously titrated homologous antiserum. The results showed that differences occurred between the viruses examined. Viruses could be grouped according to their ability to compete with the homologous virus, and statistically significant differences between virus 'groups' were observed. A comparison of the relationships between the viruses using RIA and complement fixation tests was made. The results did not always correlate. Certain homologous antigen/antibody combinations were more discriminating. The method might prove useful in the examination of a large number of field strain viruses using a well-characterized vaccine virus homologous system, particularly if the method is adapted to use antisera specific for the neutralizing antigen of the homologous test virus."}
{"id": "PMID:198287", "title": "[Classification of strains of foot-and-mouth disease virus according to the relationship-dominance model for a better understanding of the concept of serologic and immunologic subtype].", "content": "The homologous and heterologous serological titers of a specific serum can be integrated in a bidimensional system which characterizes the criteria of relationship and dominace. This bidimensional classification specifies more precisely the serological properties of each strain compared with the others (taxonomic purpose) and allows eventual guidance in the choice of vaccinal strains (epizootiologic and prophylactic purposes).", "contents": "[Classification of strains of foot-and-mouth disease virus according to the relationship-dominance model for a better understanding of the concept of serologic and immunologic subtype]. The homologous and heterologous serological titers of a specific serum can be integrated in a bidimensional system which characterizes the criteria of relationship and dominace. This bidimensional classification specifies more precisely the serological properties of each strain compared with the others (taxonomic purpose) and allows eventual guidance in the choice of vaccinal strains (epizootiologic and prophylactic purposes)."}
{"id": "PMID:198290", "title": "A survey of FMD type 'O' strains from the Far East.", "content": "A survey of 'O' strains submitted from Far Eastern countries has been conducted, comparing the strains with standard reference strains and with each other. The results indicate differences between these strains but they cannot be arranged in clearly distinct groups. There is, rather, a continuous variation with cross-relation between strains occurring more or less haphazardly. This makes the subgrouping of a large number of strains extremely difficult and supports the view expressed in other papers in this symposium that current concepts of subtyping should be revised to take into account multiple antigenic relationships.", "contents": "A survey of FMD type 'O' strains from the Far East. A survey of 'O' strains submitted from Far Eastern countries has been conducted, comparing the strains with standard reference strains and with each other. The results indicate differences between these strains but they cannot be arranged in clearly distinct groups. There is, rather, a continuous variation with cross-relation between strains occurring more or less haphazardly. This makes the subgrouping of a large number of strains extremely difficult and supports the view expressed in other papers in this symposium that current concepts of subtyping should be revised to take into account multiple antigenic relationships."}
{"id": "PMID:198291", "title": "Serological and immunological relationships among type A foot-and-mouth disease strains in South America.", "content": "Field strains of foot-and-mouth disease (FMD) virus which differ immunogenically from vaccine strains appear from time to time and may present serious problems for FMD campaigns. In order that appropriate measures can be taken it is important to determine the degree of differences between the vaccine strain and the variant strain soon after its appearance. With the A strains studied it was observed that a serological relationship by complement fixation test of greater than or equal to 0.40 would indicate sufficient protection of the vaccine strain for the field strain. With a lower relationship, however, the vaccine strains usually do not fully protect against the field strain. The mouse protection test can be used to determine how serious the lack of protection may be. With this test routine it is possible to issue alerts for intensified epidemiological surveillance within 2-3 weeks after the field strain is received at the Center.", "contents": "Serological and immunological relationships among type A foot-and-mouth disease strains in South America. Field strains of foot-and-mouth disease (FMD) virus which differ immunogenically from vaccine strains appear from time to time and may present serious problems for FMD campaigns. In order that appropriate measures can be taken it is important to determine the degree of differences between the vaccine strain and the variant strain soon after its appearance. With the A strains studied it was observed that a serological relationship by complement fixation test of greater than or equal to 0.40 would indicate sufficient protection of the vaccine strain for the field strain. With a lower relationship, however, the vaccine strains usually do not fully protect against the field strain. The mouse protection test can be used to determine how serious the lack of protection may be. With this test routine it is possible to issue alerts for intensified epidemiological surveillance within 2-3 weeks after the field strain is received at the Center."}
{"id": "PMID:198293", "title": "New media and their advantages in the production of suspended cells and foot--and--mouth disease virus.", "content": "The problems related to the use of serum in cell culture are reviewed. The possibility of substituting the serum with peptones has already been shown. Different peptones have been tested: one of the best is a peptone obtained from meat and casein pepsin pancreatically digested. BHK 21/13 cells were cultivated in serum-free media for 35 passages. The 0.81 cultures without automatic pH control had a cycle length of 3 days; starting with concentrations of 0.4 X 10(6) cells/ml, concentrations higher than 3 X 10(6) cells/ml were often obtained. We did not obtain satisfactory results when the volume of cultivation was increased to more than 6 1, perhaps because of different requirements for agitation, pH, O2. It is also necessary to check whether the results obtained up to now are consistent with reference to the source of reagents and cell strain used. The absence of serum in the medium did not influence virus replication when infectivity and complement fixation titers were tested.", "contents": "New media and their advantages in the production of suspended cells and foot--and--mouth disease virus. The problems related to the use of serum in cell culture are reviewed. The possibility of substituting the serum with peptones has already been shown. Different peptones have been tested: one of the best is a peptone obtained from meat and casein pepsin pancreatically digested. BHK 21/13 cells were cultivated in serum-free media for 35 passages. The 0.81 cultures without automatic pH control had a cycle length of 3 days; starting with concentrations of 0.4 X 10(6) cells/ml, concentrations higher than 3 X 10(6) cells/ml were often obtained. We did not obtain satisfactory results when the volume of cultivation was increased to more than 6 1, perhaps because of different requirements for agitation, pH, O2. It is also necessary to check whether the results obtained up to now are consistent with reference to the source of reagents and cell strain used. The absence of serum in the medium did not influence virus replication when infectivity and complement fixation titers were tested."}
{"id": "PMID:198294", "title": "[Methods of testing of safety of the anti-foot-and-mouth disease vaccine].", "content": "Innocuity testing in bovines remains the reference method but other methods using mice and especially cell cultures may be employed. Different techniques (dialysis, neutralization, elution, etc.) allow the elimination of toxic constituents of the vaccine while respecting the eventual presence of small quantities of active virus. The sensitivity of the cell cultures is certainly equal if not superior to that of the tongue of bovines. Interference phenomena do not intervene and, furthermore, there is not reason to fear them solely on cell cultures. From the purely statistical standpoint, it is hardly possible to prove the innocuity of a vaccine but the credit which sould be accorded to the innocuity test can be reinforced by a good control of the inactivation process and, a posteriori, by the repetition of negative results.", "contents": "[Methods of testing of safety of the anti-foot-and-mouth disease vaccine]. Innocuity testing in bovines remains the reference method but other methods using mice and especially cell cultures may be employed. Different techniques (dialysis, neutralization, elution, etc.) allow the elimination of toxic constituents of the vaccine while respecting the eventual presence of small quantities of active virus. The sensitivity of the cell cultures is certainly equal if not superior to that of the tongue of bovines. Interference phenomena do not intervene and, furthermore, there is not reason to fear them solely on cell cultures. From the purely statistical standpoint, it is hardly possible to prove the innocuity of a vaccine but the credit which sould be accorded to the innocuity test can be reinforced by a good control of the inactivation process and, a posteriori, by the repetition of negative results."}
{"id": "PMID:198296", "title": "Investigations on the suitability of mice for potency testing of FMD vaccines.", "content": "Potency testing of FMD vaccines by a three-point method was elaborated. Mice myotropic FMD virus was used as challenge virus. With this test the immunogenicity of FMD vaccines based on BHK, calf kidney or swine kidney was examined. The results are reproducible and allow quantification of the antigenic value of FMD vaccines within statistical limits.", "contents": "Investigations on the suitability of mice for potency testing of FMD vaccines. Potency testing of FMD vaccines by a three-point method was elaborated. Mice myotropic FMD virus was used as challenge virus. With this test the immunogenicity of FMD vaccines based on BHK, calf kidney or swine kidney was examined. The results are reproducible and allow quantification of the antigenic value of FMD vaccines within statistical limits."}
{"id": "PMID:198297", "title": "Studies on the correct quantitative relations of antigen components in mono-, bi- and trivalent foot-and-mouth disease vaccine preparations.", "content": "Waldmann and frenkel type mono-, bi- and trivalent FMD vaccines, with different quantitative relations of the antigen components, were prepared and tested by the E, K and S index methods. Potency tests in adult mice showed that the antigen components of the bivalent vaccines are usually synergistic, but a 47-57% excess of antigen \"O1\" over the other two types is always required for a similar immunogenic action (E index value). For the same reason, the \"O1\" content of the trivalent vaccine should be as high as the total quantity of its other two components. Trivalent FMD vaccines in which the quantitative relations of the antigen components correspond with the proportions assessed as optimal in the mouse test prove also to be satisfactorily immunogenic in cattle in respect of all three components.", "contents": "Studies on the correct quantitative relations of antigen components in mono-, bi- and trivalent foot-and-mouth disease vaccine preparations. Waldmann and frenkel type mono-, bi- and trivalent FMD vaccines, with different quantitative relations of the antigen components, were prepared and tested by the E, K and S index methods. Potency tests in adult mice showed that the antigen components of the bivalent vaccines are usually synergistic, but a 47-57% excess of antigen \"O1\" over the other two types is always required for a similar immunogenic action (E index value). For the same reason, the \"O1\" content of the trivalent vaccine should be as high as the total quantity of its other two components. Trivalent FMD vaccines in which the quantitative relations of the antigen components correspond with the proportions assessed as optimal in the mouse test prove also to be satisfactorily immunogenic in cattle in respect of all three components."}
{"id": "PMID:198298", "title": "Determination of antigen content and effectiveness of foor-and-mouth disease vaccines.", "content": "The following paragraphs are in reality the conclusion of a communication which was not presented at the symposium owing to Dr Czelleng's absence. Taking the place of his colleague, Dr S\u00f3lyom gave a brief account of the complement fixation test in the estimation of immunity against foot-and-mouth disease. The test conditions are improved by using a standardized complement; this method allows to meausre very precisely the amount of antigen used for the production of vaccine.", "contents": "Determination of antigen content and effectiveness of foor-and-mouth disease vaccines. The following paragraphs are in reality the conclusion of a communication which was not presented at the symposium owing to Dr Czelleng's absence. Taking the place of his colleague, Dr S\u00f3lyom gave a brief account of the complement fixation test in the estimation of immunity against foot-and-mouth disease. The test conditions are improved by using a standardized complement; this method allows to meausre very precisely the amount of antigen used for the production of vaccine."}
{"id": "PMID:198299", "title": "Attempts at potency testing of foot-and-mouth disease vaccines by evaluation of the complement fixing capacity of eluates.", "content": "A method has been developed to evaluate the amount of antigen in foot-and-mouth disease vaccines by complement fixation after elution from aluminum hydroxide. The 12 S antigen is eliminated by treatment with Arcton 119 so that only the 140 S antigen may be determined. The concentration of 140 S antigen eluted from the vaccine is compared with the degree of protection conferred to cattle. 333 heads of cattle were vaccinated with 111 vaccines containing detectable amounts of 140 S antigen. Only one animal was not protected. In a repeated test of the questionable vaccine with 6 animals all were found to be protected. From 32 vaccines the amount of eluted 140 S antigen was compared with the PD50 in guinea pigs. Ten vaccines from 11 without detectable 140 S antigen had a PD50 value in guinea pigs lower than the limit indicating a satisfying potency for cattle.", "contents": "Attempts at potency testing of foot-and-mouth disease vaccines by evaluation of the complement fixing capacity of eluates. A method has been developed to evaluate the amount of antigen in foot-and-mouth disease vaccines by complement fixation after elution from aluminum hydroxide. The 12 S antigen is eliminated by treatment with Arcton 119 so that only the 140 S antigen may be determined. The concentration of 140 S antigen eluted from the vaccine is compared with the degree of protection conferred to cattle. 333 heads of cattle were vaccinated with 111 vaccines containing detectable amounts of 140 S antigen. Only one animal was not protected. In a repeated test of the questionable vaccine with 6 animals all were found to be protected. From 32 vaccines the amount of eluted 140 S antigen was compared with the PD50 in guinea pigs. Ten vaccines from 11 without detectable 140 S antigen had a PD50 value in guinea pigs lower than the limit indicating a satisfying potency for cattle."}
{"id": "PMID:198300", "title": "[Routine physico-chemical testing of concentrated virulent and inactivated foot-and-mouth disease virus antigens].", "content": "The ponderal quantity of 140 S antigens and their peptide distribution are controlled in concentrated virulent and inactivated preparations proir to their being transformed into vaccines. A certain variability in the amount of 140 S particles and in the titer of peptide sensitive to trypsin (VP1) has been demonstrated in the virulent preparations. After treatment by inactivating agents (glycidaldehyde, binary ethyleneimine and formaldehyde) two types of alteration of the viral capsid are shown : one leads to the partial cleavage of VP1 (glycidaldehyde and binary ethyleneimine), the other leads to the detaching of an important quantity of VP1 from the capsid (formaldehyde). The degradation by formadehyde of the 140 S particles of type O and type C into 12 S particles is underlined, as well as the relatuve stability of type A and the relatuve lability of type C. The results are discussed in terms of immunogenicity.", "contents": "[Routine physico-chemical testing of concentrated virulent and inactivated foot-and-mouth disease virus antigens]. The ponderal quantity of 140 S antigens and their peptide distribution are controlled in concentrated virulent and inactivated preparations proir to their being transformed into vaccines. A certain variability in the amount of 140 S particles and in the titer of peptide sensitive to trypsin (VP1) has been demonstrated in the virulent preparations. After treatment by inactivating agents (glycidaldehyde, binary ethyleneimine and formaldehyde) two types of alteration of the viral capsid are shown : one leads to the partial cleavage of VP1 (glycidaldehyde and binary ethyleneimine), the other leads to the detaching of an important quantity of VP1 from the capsid (formaldehyde). The degradation by formadehyde of the 140 S particles of type O and type C into 12 S particles is underlined, as well as the relatuve stability of type A and the relatuve lability of type C. The results are discussed in terms of immunogenicity."}
{"id": "PMID:198301", "title": "[Immunogenic quality of foot-and-mouth disease virus].", "content": "Routine analysis of suspensions of foot-and-mouth disease virus and eluates of vaccine by the isopycnic method in analytical ultracentrifuge demonstrates the important heterogeneity of the viral population. This heterogeneity increases during inactivation of the virus by formol. In view of this dispersion of the physical characteristics of viral particles it may be asked (a) whether the immunogenic value is linked to the total quantity of particles which, we know, are very different from each other and of which we can determine only the partial or total parameters or (b) whether, on the contrary, the immunogenic value is linked to the activity of marginal particles, very small in number, and perhaps even quantitatively indistinguishable by the physical methods available. However, the hypothesis of particles possessing different properties but converging in the final result cannot, a priori, be excluded. Consequently it cannot be hoped that a simple relation between the concentration in weight of a viral suspension and its immunogenic property may be determined.", "contents": "[Immunogenic quality of foot-and-mouth disease virus]. Routine analysis of suspensions of foot-and-mouth disease virus and eluates of vaccine by the isopycnic method in analytical ultracentrifuge demonstrates the important heterogeneity of the viral population. This heterogeneity increases during inactivation of the virus by formol. In view of this dispersion of the physical characteristics of viral particles it may be asked (a) whether the immunogenic value is linked to the total quantity of particles which, we know, are very different from each other and of which we can determine only the partial or total parameters or (b) whether, on the contrary, the immunogenic value is linked to the activity of marginal particles, very small in number, and perhaps even quantitatively indistinguishable by the physical methods available. However, the hypothesis of particles possessing different properties but converging in the final result cannot, a priori, be excluded. Consequently it cannot be hoped that a simple relation between the concentration in weight of a viral suspension and its immunogenic property may be determined."}
{"id": "PMID:198302", "title": "An evalutation of some methods of assay of foot-and-mouth disease antigen for vaccines.", "content": "The relative merits of various in vitro assay systems for the measurement of the quality and quantity of foot-and-mouth disease virus vaccine antigen will be discussed. The assay systems include : viral infectivity, complement fixing activity, particle counts, radial diffusion titre and single radial haemolysis titre. The predictive value of the tests for the immunogenicity of the final vaccine product will be evaluated against the results of 50% Protective Dose titres determined in guinea pigs and cattle by antibody assay and by challenge.", "contents": "An evalutation of some methods of assay of foot-and-mouth disease antigen for vaccines. The relative merits of various in vitro assay systems for the measurement of the quality and quantity of foot-and-mouth disease virus vaccine antigen will be discussed. The assay systems include : viral infectivity, complement fixing activity, particle counts, radial diffusion titre and single radial haemolysis titre. The predictive value of the tests for the immunogenicity of the final vaccine product will be evaluated against the results of 50% Protective Dose titres determined in guinea pigs and cattle by antibody assay and by challenge."}
{"id": "PMID:198306", "title": "[Testing the activity of anti-foot-and-mouth disease vaccine in cattle: quantitative methods of antigenic extinction].", "content": "Two methods of evaluating the activity of the foot-and-mouth disease vaccine are compared, leading to the evaluation of the number of protective doses 50% or potency. These methods differ in sensitivity, precision and equivalence potency-percentage of protection. For the same vaccine the value of the PD50 is always larger than that of Pb. We chose the Pb method using a diluent containing no adjuvant. Standards based on the evaluation of average potency have not been taken into consideration; only those standards based on the evaluation of minimum potency ensure respect of OIE's recommendation. This recommendation: 70% minimum potency with 0.95 probability is not an easier alternative, since the average protection observed corresponds in fact to at least 90% taking into account the biological variability of bovines.", "contents": "[Testing the activity of anti-foot-and-mouth disease vaccine in cattle: quantitative methods of antigenic extinction]. Two methods of evaluating the activity of the foot-and-mouth disease vaccine are compared, leading to the evaluation of the number of protective doses 50% or potency. These methods differ in sensitivity, precision and equivalence potency-percentage of protection. For the same vaccine the value of the PD50 is always larger than that of Pb. We chose the Pb method using a diluent containing no adjuvant. Standards based on the evaluation of average potency have not been taken into consideration; only those standards based on the evaluation of minimum potency ensure respect of OIE's recommendation. This recommendation: 70% minimum potency with 0.95 probability is not an easier alternative, since the average protection observed corresponds in fact to at least 90% taking into account the biological variability of bovines."}
{"id": "PMID:198308", "title": "[Combined vaccines including 1 or several anti-foot-and-mouth valences].", "content": "Combined vaccines are used  for many human and animal diseases. However, we have very few examples of combinations containing anti-foot-and-mouth valence which would allow easy immunization against differnet diseases without additional handling. Until now foot-and-mouth vaccination has been applied simultaneously with anti-brucellic vaccination (Baldoni, Renoux), andi-anthrax (Nobili) and vaccination against swine fever and Aujeszky's disease (Lysenko). During the last ten years we have particularly studied the association of anti-foot-and-mouth disease vaccines with anti-brucella and anti-rabies vaccines. We have shown the possiblity of combining these different antigens, either in classical aqueous vaccines in aluminum hydroxide, or in emulsified vaccines containing oily adjuvants. The anti-brucella valences may be agglutinogenic (H 38) or non-agglutinogenic (MacEwen 45/20). The combined vaccines \"rabies + foot-and-mouth disease\" and \"brucellosis + foot-and-mouth disease\" can be produced on an industrial scale. For many years millions of animals have been successfully vaccinated in France by means of a combined \"rabies + foot-and-mouth disease\" vaccine.", "contents": "[Combined vaccines including 1 or several anti-foot-and-mouth valences]. Combined vaccines are used  for many human and animal diseases. However, we have very few examples of combinations containing anti-foot-and-mouth valence which would allow easy immunization against differnet diseases without additional handling. Until now foot-and-mouth vaccination has been applied simultaneously with anti-brucellic vaccination (Baldoni, Renoux), andi-anthrax (Nobili) and vaccination against swine fever and Aujeszky's disease (Lysenko). During the last ten years we have particularly studied the association of anti-foot-and-mouth disease vaccines with anti-brucella and anti-rabies vaccines. We have shown the possiblity of combining these different antigens, either in classical aqueous vaccines in aluminum hydroxide, or in emulsified vaccines containing oily adjuvants. The anti-brucella valences may be agglutinogenic (H 38) or non-agglutinogenic (MacEwen 45/20). The combined vaccines \"rabies + foot-and-mouth disease\" and \"brucellosis + foot-and-mouth disease\" can be produced on an industrial scale. For many years millions of animals have been successfully vaccinated in France by means of a combined \"rabies + foot-and-mouth disease\" vaccine."}
{"id": "PMID:198309", "title": "[Anti-foot-and-mouth vaccines combined with other bacterial or viral vaccines].", "content": "Medical and sanitary prevention of a growing number of major infectious diseases of bovines has led IFFA-M\u00e9rieux to investigate the association of vaccines and to define methods of utilization. Care has been taken to limit the number of interventions and at the same time to retain in the combined valences the efficacy they had when in a state of single constituent. The work which has been carried out for the last ten years, including the study of adjuvants as well as of incompatibility of associations, has permitted the improvement of formulas, reduced in volume (5 ml for a plurivalent dose), in aqueous excipient (aluminum hydroxide and saponin) or oily excipient (oil in water type). These formulas combine 3 foot-and-mouth disease valences with a rabies valence (fixed strain grown on cell culture) or with a brucellosis valence (strain B. abortus MacEwen 45/20 and B. melitensis H 38). The innocuity of these associations allows them to be used in sanitary compaigns; their efficacy is equal to that of monovalent vaccines. A logical vaccination calendar is proposed.", "contents": "[Anti-foot-and-mouth vaccines combined with other bacterial or viral vaccines]. Medical and sanitary prevention of a growing number of major infectious diseases of bovines has led IFFA-M\u00e9rieux to investigate the association of vaccines and to define methods of utilization. Care has been taken to limit the number of interventions and at the same time to retain in the combined valences the efficacy they had when in a state of single constituent. The work which has been carried out for the last ten years, including the study of adjuvants as well as of incompatibility of associations, has permitted the improvement of formulas, reduced in volume (5 ml for a plurivalent dose), in aqueous excipient (aluminum hydroxide and saponin) or oily excipient (oil in water type). These formulas combine 3 foot-and-mouth disease valences with a rabies valence (fixed strain grown on cell culture) or with a brucellosis valence (strain B. abortus MacEwen 45/20 and B. melitensis H 38). The innocuity of these associations allows them to be used in sanitary compaigns; their efficacy is equal to that of monovalent vaccines. A logical vaccination calendar is proposed."}
{"id": "PMID:198310", "title": "Simultaneous vaccination of cattle with foot-and-mouth disease and vesicular stomatitis live virus vaccines.", "content": "Four- to six- month-old cattle were simultaneously vaccinated with foot-and-mouth disease (FMD) and vesicular stomatitis (VS) live virus vaccines by injection of FMD vaccine in one side of the body and VS vaccine in the other side. These cattle were again vaccinated with FMD and VS vaccines given simultaneously three and nine months after the first vaccination. The antibody levels of the vaccinated animals were studied by serum protection test in suckling mice and results were compared with those obtained when cattle are vaccinated either with FMD alone or with VS vaccine alone. It appears that an interference mechanism is responsible for the lack or the low levels of antibody formation observed in the animals simultaneoulsy vaccinated with the two vaccines.", "contents": "Simultaneous vaccination of cattle with foot-and-mouth disease and vesicular stomatitis live virus vaccines. Four- to six- month-old cattle were simultaneously vaccinated with foot-and-mouth disease (FMD) and vesicular stomatitis (VS) live virus vaccines by injection of FMD vaccine in one side of the body and VS vaccine in the other side. These cattle were again vaccinated with FMD and VS vaccines given simultaneously three and nine months after the first vaccination. The antibody levels of the vaccinated animals were studied by serum protection test in suckling mice and results were compared with those obtained when cattle are vaccinated either with FMD alone or with VS vaccine alone. It appears that an interference mechanism is responsible for the lack or the low levels of antibody formation observed in the animals simultaneoulsy vaccinated with the two vaccines."}
{"id": "PMID:198311", "title": "[Preliminary study of the combination of anti-foot-and-mouth disease and anti-brucellosis vaccines].", "content": "The results obtained with Brucella B19 strain, used as adjuvant and stimulant in the preparation of hyperimmune anti-foot-and-mouth disease serums on guinea pigs, have led the authors to carry out a series of experiments with a combined anti-foot-and-mouth disease and anti-brucellosis vaccine (strain B 19 Buck and Cotton). The search for neutralizing antibodies for foot-and-mouth disease has been undertaken by different methods. In the search for antibrucellic antibodies reactions such as seroagglutination, fixation of the complement, etc. have been used. The results obtained with combined vaccine are identical with those obtained with each of the monovalent vaccines.", "contents": "[Preliminary study of the combination of anti-foot-and-mouth disease and anti-brucellosis vaccines]. The results obtained with Brucella B19 strain, used as adjuvant and stimulant in the preparation of hyperimmune anti-foot-and-mouth disease serums on guinea pigs, have led the authors to carry out a series of experiments with a combined anti-foot-and-mouth disease and anti-brucellosis vaccine (strain B 19 Buck and Cotton). The search for neutralizing antibodies for foot-and-mouth disease has been undertaken by different methods. In the search for antibrucellic antibodies reactions such as seroagglutination, fixation of the complement, etc. have been used. The results obtained with combined vaccine are identical with those obtained with each of the monovalent vaccines."}
{"id": "PMID:198312", "title": "One year experience on the Lindholm B medium used in large--scale FMD virus production on BHK cells in suspension.", "content": "The propagation of FMD virus on BHK 21 clone 13 suspension cells was based on the Lindholm B medium during the production period August 1975 to June 1976. The medium was used in connection with a production cycle including decreasing amounts of serum in the cell growth medium and inoculation of the cells while they were still in growth. This method of virus production, compared with the traditional method, is cheaper due to the lowered medium cost. The improved utilization of the fermenter capacity and the decreased consumption of serum have practical as well as economic aspects. The results obtained during the period indicate that virus production by this method is reliable and at least on the same level as by traditional methods.", "contents": "One year experience on the Lindholm B medium used in large--scale FMD virus production on BHK cells in suspension. The propagation of FMD virus on BHK 21 clone 13 suspension cells was based on the Lindholm B medium during the production period August 1975 to June 1976. The medium was used in connection with a production cycle including decreasing amounts of serum in the cell growth medium and inoculation of the cells while they were still in growth. This method of virus production, compared with the traditional method, is cheaper due to the lowered medium cost. The improved utilization of the fermenter capacity and the decreased consumption of serum have practical as well as economic aspects. The results obtained during the period indicate that virus production by this method is reliable and at least on the same level as by traditional methods."}
{"id": "PMID:198314", "title": "Certain aspects of foot--and--mouth disease. Virus production in growing BHK suspended cell cultures.", "content": "Production of FMDV in growing BHK suspended cell cultures offers several technical advantages: no medium change and no sedimentation of cells prior to infection are needed, thus saving time and medium. However, the final product should be as free of serum proteins as possible. For this purpose polyethylene-glycol-(PEG)-treated serum can be used for the stimulation of cell growth in combination with precipitation of the virus with PEG. With this method virus preparations are obtained in which practically no serum proteins can be estimated. Recently the use of serum-free medium has been reported for a BHK line which had been adapted to this medium. This also offers possibilities of virus cultivation in growing cells. Two of our BHK lines also grow in a cheap serum-free medium in which amino acids are replaced by a combination of lactalbumin hydrolysate and peptic peptone. With BHK cells adapted to this medium high cell yields are obtained. The use of PEG-treated serum will be compared with the use of the low cost serum-free medium with respect to FMDV production.", "contents": "Certain aspects of foot--and--mouth disease. Virus production in growing BHK suspended cell cultures. Production of FMDV in growing BHK suspended cell cultures offers several technical advantages: no medium change and no sedimentation of cells prior to infection are needed, thus saving time and medium. However, the final product should be as free of serum proteins as possible. For this purpose polyethylene-glycol-(PEG)-treated serum can be used for the stimulation of cell growth in combination with precipitation of the virus with PEG. With this method virus preparations are obtained in which practically no serum proteins can be estimated. Recently the use of serum-free medium has been reported for a BHK line which had been adapted to this medium. This also offers possibilities of virus cultivation in growing cells. Two of our BHK lines also grow in a cheap serum-free medium in which amino acids are replaced by a combination of lactalbumin hydrolysate and peptic peptone. With BHK cells adapted to this medium high cell yields are obtained. The use of PEG-treated serum will be compared with the use of the low cost serum-free medium with respect to FMDV production."}
{"id": "PMID:198315", "title": "Studies on the susceptibility to foot--and--mouth disease virus of BHK cell cultures derived from various sources.", "content": "Cultures of BHK monolayer and suspension cells obtained from a number of laboratories and a group of cloned sub-lines derived from suspension cells were examined for their susceptibility to three FMD virus strains. It was found that the various cultures were sensitive to the test virus strains to differing degrees. It was shown possible to obtain a clone with high susceptibility to Asia 1 Iran 1/73 virus from a parent culture which had a low susceptibility to that virus. The implication of these findings is discussed.", "contents": "Studies on the susceptibility to foot--and--mouth disease virus of BHK cell cultures derived from various sources. Cultures of BHK monolayer and suspension cells obtained from a number of laboratories and a group of cloned sub-lines derived from suspension cells were examined for their susceptibility to three FMD virus strains. It was found that the various cultures were sensitive to the test virus strains to differing degrees. It was shown possible to obtain a clone with high susceptibility to Asia 1 Iran 1/73 virus from a parent culture which had a low susceptibility to that virus. The implication of these findings is discussed."}
{"id": "PMID:198316", "title": "Reproducibility of yields of foot--and--mouth disease virus from BHK monolayer and suspension cells.", "content": "The production of FMD virus from BHK 21 C13 monolayer and suspension cells was examined under standardized conditions and in different systems. The yields of virus from suspension cells did not significantly exceed the yield from monolayer cells, whereas the monolayer cell was capable of producing virus from some strains of FMD virus which would not grow in suspension cells. When different production systems were examined, the scale of operation did not significantly influence the yield of virus from suspension cells, while the plastic spiral film propagator produced significantly less virus than the other monolayer systems examined. The use of unit monolayer systems on the large scale is discussed.", "contents": "Reproducibility of yields of foot--and--mouth disease virus from BHK monolayer and suspension cells. The production of FMD virus from BHK 21 C13 monolayer and suspension cells was examined under standardized conditions and in different systems. The yields of virus from suspension cells did not significantly exceed the yield from monolayer cells, whereas the monolayer cell was capable of producing virus from some strains of FMD virus which would not grow in suspension cells. When different production systems were examined, the scale of operation did not significantly influence the yield of virus from suspension cells, while the plastic spiral film propagator produced significantly less virus than the other monolayer systems examined. The use of unit monolayer systems on the large scale is discussed."}
{"id": "PMID:198317", "title": "[Characteristics of viruses multiplying in cell lines in suspension and their correspondent vaccines].", "content": "The characteristics of the viruses produced from cell lines developed in suspension and the vaccines for which they are used should be judged by methods which allow to ensure in all cases their innocuity and efficacity. Innocuity is essentially dependent upon the purity of the viral preparation which should contain a minimum of foreign proteins (due either to the cell or the culture medium) and certain antibiotics. Furthermore, the absence of oncogenic properties of the inactivated viral suspensions should be shown, in addition to their specific innocuity. Efficacity is linked with the concentration of viral particles and with their immunogenic properties after inactivation and incorporation of adjuvants of immunity. Methods of appreciation of the different parameters are proposed.", "contents": "[Characteristics of viruses multiplying in cell lines in suspension and their correspondent vaccines]. The characteristics of the viruses produced from cell lines developed in suspension and the vaccines for which they are used should be judged by methods which allow to ensure in all cases their innocuity and efficacity. Innocuity is essentially dependent upon the purity of the viral preparation which should contain a minimum of foreign proteins (due either to the cell or the culture medium) and certain antibiotics. Furthermore, the absence of oncogenic properties of the inactivated viral suspensions should be shown, in addition to their specific innocuity. Efficacity is linked with the concentration of viral particles and with their immunogenic properties after inactivation and incorporation of adjuvants of immunity. Methods of appreciation of the different parameters are proposed."}
{"id": "PMID:198318", "title": "The use of suspension cultures for FMD vaccine production. Criteria for the evaluation of cells, virus and vaccine.", "content": "A survey of problems connected with the cell suspension culture for the production of FMD vaccine is presented, in order to stimulate a discussion. Introductory remarks are made on the following topics: 1) suspension cell lines used for FMD vaccine production, 2) terminology, 3) criteria for the characterization of a cell culture, 4) evaluation of FMD virus produced according to the cell suspension technique and correlation existing between in vitro tests and antigenicity in domestic animals, 5) criteria which must be met by FMD vaccine produced from virus cultivated on cell suspension.", "contents": "The use of suspension cultures for FMD vaccine production. Criteria for the evaluation of cells, virus and vaccine. A survey of problems connected with the cell suspension culture for the production of FMD vaccine is presented, in order to stimulate a discussion. Introductory remarks are made on the following topics: 1) suspension cell lines used for FMD vaccine production, 2) terminology, 3) criteria for the characterization of a cell culture, 4) evaluation of FMD virus produced according to the cell suspension technique and correlation existing between in vitro tests and antigenicity in domestic animals, 5) criteria which must be met by FMD vaccine produced from virus cultivated on cell suspension."}
{"id": "PMID:198319", "title": "[Allergic reactions in cattle vaccinated against foot-and-mouth disease with vaccines prepared from viruses cultivated in BHK cells in roller bottles].", "content": "Tests on bovines vaccinated 3 or 4 times against foot-and-mouth disease with vaccines based on viruses cultivated on BKH cells, in roller bottles, have allowed to define the nature of some of the principal allergens: on the one hand residuary horse serum used to saturate the filters employed in preparing the virus intended for the manufacture of vaccines and, on the other hand, the substances liberated by the cytopathogenic action of the virus on the BHK cells. The horse serum is the most active and causes general and local reactions which are sometimes severe. It is therefore replaced by calf serum intended to reduce the importance of the problem for bovines. BHK antigens (BHK extracts and virus) produce only local reactions which are generally less severe.", "contents": "[Allergic reactions in cattle vaccinated against foot-and-mouth disease with vaccines prepared from viruses cultivated in BHK cells in roller bottles]. Tests on bovines vaccinated 3 or 4 times against foot-and-mouth disease with vaccines based on viruses cultivated on BKH cells, in roller bottles, have allowed to define the nature of some of the principal allergens: on the one hand residuary horse serum used to saturate the filters employed in preparing the virus intended for the manufacture of vaccines and, on the other hand, the substances liberated by the cytopathogenic action of the virus on the BHK cells. The horse serum is the most active and causes general and local reactions which are sometimes severe. It is therefore replaced by calf serum intended to reduce the importance of the problem for bovines. BHK antigens (BHK extracts and virus) produce only local reactions which are generally less severe."}
{"id": "PMID:198320", "title": "Critical factors of the vacuum-oven technique which influence the estimation of moisture in veterinary biologics.", "content": "When striving toward standardization of lyophilized products, it is often difficult to correlate biological characteristics and residual-moisture content because of the great variety of assay procedures being used to estimate residual moisture. Even when moisture assays are performed according to the same general assay procedure, there are often subtle differences that cause large variations in results. Critical factors of the vacuum-oven technique such as: homogeneity and number of samples, size of samples, moisture adsorption of dry weighing dishes, efficacy of disiccator jars, influence of ambient conditions, controlling time-sequence of the test, tolerances of the test, etc. are discussed and data presented to demonstrate how some of these factors can strongly influence the results of the assay. The validity of the assay and the subsequent judgement about the quality of the final product are greatly dependent upon how well these factors are controlled.", "contents": "Critical factors of the vacuum-oven technique which influence the estimation of moisture in veterinary biologics. When striving toward standardization of lyophilized products, it is often difficult to correlate biological characteristics and residual-moisture content because of the great variety of assay procedures being used to estimate residual moisture. Even when moisture assays are performed according to the same general assay procedure, there are often subtle differences that cause large variations in results. Critical factors of the vacuum-oven technique such as: homogeneity and number of samples, size of samples, moisture adsorption of dry weighing dishes, efficacy of disiccator jars, influence of ambient conditions, controlling time-sequence of the test, tolerances of the test, etc. are discussed and data presented to demonstrate how some of these factors can strongly influence the results of the assay. The validity of the assay and the subsequent judgement about the quality of the final product are greatly dependent upon how well these factors are controlled."}
{"id": "PMID:198321", "title": "Plasma cyclic nucleotide levels in juvenile-onset diabetes.", "content": "In patients with juvenile-onset diabetes, plasma concentrations of 3',5'-adenosine cyclic monophosphate (cAMP) were significantly lower than those of norman subjects [16 +/- 4 and 24 +/- 7 pmol per milliliter (p less than 0.025), respectively] as determined in this laboratory; whereas there were essentially no differences in plasma levels of 3',5'-guanosine cyclic monophosphate (cGMP). Because cAMP inhibits cell growth and cGMP stimulates it, these findings may represent an important factor in the atherosclerotic and obliterative angiopathies of diabetic individuals. We observed that cyclic nucleotide values were the same whether or not the subjects were receiving insulin. Those given insulin plus enough glucose to maintain hyperglycemia revealed modest elevations in cyclic nucleotide levels. Thus, the ratio of cAMP to cGMP, abnormally low in juvenile-onset diabetes, is relatively independent of short-term variations in plasma levels of either glucose of insulin.", "contents": "Plasma cyclic nucleotide levels in juvenile-onset diabetes. In patients with juvenile-onset diabetes, plasma concentrations of 3',5'-adenosine cyclic monophosphate (cAMP) were significantly lower than those of norman subjects [16 +/- 4 and 24 +/- 7 pmol per milliliter (p less than 0.025), respectively] as determined in this laboratory; whereas there were essentially no differences in plasma levels of 3',5'-guanosine cyclic monophosphate (cGMP). Because cAMP inhibits cell growth and cGMP stimulates it, these findings may represent an important factor in the atherosclerotic and obliterative angiopathies of diabetic individuals. We observed that cyclic nucleotide values were the same whether or not the subjects were receiving insulin. Those given insulin plus enough glucose to maintain hyperglycemia revealed modest elevations in cyclic nucleotide levels. Thus, the ratio of cAMP to cGMP, abnormally low in juvenile-onset diabetes, is relatively independent of short-term variations in plasma levels of either glucose of insulin."}
{"id": "PMID:198322", "title": "Cyclic nucleotide phosphodiesterase. Insulin activation detected in adipose tissue by gel electrophoresis.", "content": "In rat adipose tissue, insulin (100 muU./ml.) increases the activity of cyclic AMP (but not cyclic GMP) phosphodiesterase (PDE). Radioisotopic assay, autoradiography, and histochemical stains demonstrated that cyclic nucleotide PDE activity is associated with multiple bands of protein separable by polyacrylamide gel electrophoresis. The insulin activation of cyclic AMP PDE, however, was limited to a single band corresponding to the \"low\" Km enzyme specific for cyclic AMP; insulin had no effect on the \"high\" Km enzyme or on PDE bands with activity directed toward cyclic GMP. These data support the concept that insulin may modulate the activity of at least one of the cyclic AMP phosphodiesterases.", "contents": "Cyclic nucleotide phosphodiesterase. Insulin activation detected in adipose tissue by gel electrophoresis. In rat adipose tissue, insulin (100 muU./ml.) increases the activity of cyclic AMP (but not cyclic GMP) phosphodiesterase (PDE). Radioisotopic assay, autoradiography, and histochemical stains demonstrated that cyclic nucleotide PDE activity is associated with multiple bands of protein separable by polyacrylamide gel electrophoresis. The insulin activation of cyclic AMP PDE, however, was limited to a single band corresponding to the \"low\" Km enzyme specific for cyclic AMP; insulin had no effect on the \"high\" Km enzyme or on PDE bands with activity directed toward cyclic GMP. These data support the concept that insulin may modulate the activity of at least one of the cyclic AMP phosphodiesterases."}
{"id": "PMID:198323", "title": "Virus induced diabetes and the immune system. I. Suggestion that appearance of diabetes depends on immune reactions.", "content": "The participation of immune reactions in the EMC virus induced diabetes of the mouse was studied by immunosuppression with 500 R sublethal X-irradiation or 120 mg/kg Asta 5122, a cyclophosphamide derivative. Average glucose levels after X-irradiation and infection remained normal, while virus, infected, otherwise untreated mice, had significantly higher mean glucose levels, indicating that immune reactions are necessary for the development of virus induced diabetes. Immune suppression by the cyclophosphamide derivative led, in contrast, to a significantly increased mean glucose level and increased insulitis in comparison with the controls only infected. This indicates an important role of the cellular immune reaction, insulitis in the destruction of the islets.", "contents": "Virus induced diabetes and the immune system. I. Suggestion that appearance of diabetes depends on immune reactions. The participation of immune reactions in the EMC virus induced diabetes of the mouse was studied by immunosuppression with 500 R sublethal X-irradiation or 120 mg/kg Asta 5122, a cyclophosphamide derivative. Average glucose levels after X-irradiation and infection remained normal, while virus, infected, otherwise untreated mice, had significantly higher mean glucose levels, indicating that immune reactions are necessary for the development of virus induced diabetes. Immune suppression by the cyclophosphamide derivative led, in contrast, to a significantly increased mean glucose level and increased insulitis in comparison with the controls only infected. This indicates an important role of the cellular immune reaction, insulitis in the destruction of the islets."}
{"id": "PMID:198329", "title": "Metabolic and membrane aspects of gastric H+ transport.", "content": "Metabolic properties of dog gastric mucosa, investigated by substrate level measurements, implicate the Krebs cycle as the major energy-yielding metabolic pathway but are equivocal in terms of an ATP-based H+ secretion. Purification of gastric membranes by centrifugation and free flow electrophoresis results in a class of membrane vesicles enriched in K+-ATPase and capable of ATP-energized H+ uptake. Immunohistochemistry shows these to be derived from the parietal cell. H+ uptake by the vesicles is accompanied by K+ efflux, and movement of either ion is not potential-coupled. The simplest interpretation of these transport studies is uptake of KCl by the vesicles by passive diffusion followed by active H+:K+ exchange. In some respects, however, this model fails to conform to the expectations from in vitro studies. It may be, therefore, that another pump (i.e., redox) or another membrane component (i.e., Cl- conductance) is lost during purification. The properties of the vesicles are such, however, as to establish their role in H+ secretion by the stomach.", "contents": "Metabolic and membrane aspects of gastric H+ transport. Metabolic properties of dog gastric mucosa, investigated by substrate level measurements, implicate the Krebs cycle as the major energy-yielding metabolic pathway but are equivocal in terms of an ATP-based H+ secretion. Purification of gastric membranes by centrifugation and free flow electrophoresis results in a class of membrane vesicles enriched in K+-ATPase and capable of ATP-energized H+ uptake. Immunohistochemistry shows these to be derived from the parietal cell. H+ uptake by the vesicles is accompanied by K+ efflux, and movement of either ion is not potential-coupled. The simplest interpretation of these transport studies is uptake of KCl by the vesicles by passive diffusion followed by active H+:K+ exchange. In some respects, however, this model fails to conform to the expectations from in vitro studies. It may be, therefore, that another pump (i.e., redox) or another membrane component (i.e., Cl- conductance) is lost during purification. The properties of the vesicles are such, however, as to establish their role in H+ secretion by the stomach."}
{"id": "PMID:198332", "title": "Effect of cholecystokinin variant (CCK39) on dispersed acinar cells from guinea pig pancreas.", "content": "In dispersed acinar cells from guinea pig pancreas, cholecystokinin variants (CCK39 and CCK33) or carboxyl-terminal octapeptide of cholecystokinin (CCK-OP) caused significant increases in outflux of 45Ca, cyclic GMP, and release of amylase. In homogenates of acinar cells each peptide caused a significant increase in adenylate cyclase activity. For each function tested (1) CCK39 was equipotent with with CCK33, (2) CCK39 and CCK33 were 10 to 30 times less potent than CCK-OP, (3) the efficacies of CCK39, CCK33, and CCK-OP were the same, and (4) none of these effects were altered by concentrations of atropine sufficient to abolish the action of muscarinic cholinergic agents.", "contents": "Effect of cholecystokinin variant (CCK39) on dispersed acinar cells from guinea pig pancreas. In dispersed acinar cells from guinea pig pancreas, cholecystokinin variants (CCK39 and CCK33) or carboxyl-terminal octapeptide of cholecystokinin (CCK-OP) caused significant increases in outflux of 45Ca, cyclic GMP, and release of amylase. In homogenates of acinar cells each peptide caused a significant increase in adenylate cyclase activity. For each function tested (1) CCK39 was equipotent with with CCK33, (2) CCK39 and CCK33 were 10 to 30 times less potent than CCK-OP, (3) the efficacies of CCK39, CCK33, and CCK-OP were the same, and (4) none of these effects were altered by concentrations of atropine sufficient to abolish the action of muscarinic cholinergic agents."}
{"id": "PMID:198333", "title": "Distribution of intrinsic factor-vitamin B12 receptors in human intestine.", "content": "A new rapid and accurate method for detecting vitamin B12-intrinsic factor (IF-B12) receptors was used to study the distribution of mucosal IF-B12 receptors in three human small intestines. IF-B12 receptors in human intestine are present in significant amounts in the entire distal three-fifths of intestine. Triokinase activity is absent in the distal two-fifths of intestine, and tryptophan oxygenase is present only in the distal one-sixth, or most terminal part of the ileum. These data suggest (1) biochemical functions in the ileum have different anatomical distributions, (2) IF-B12 receptors correspond most closely with the accepted anatomical definitions of the ileum, and (3) vitamin B12 malabsorption seen in resection or disease of terminal ileum may not be attributable solely to a deficiency of ileal receptors.", "contents": "Distribution of intrinsic factor-vitamin B12 receptors in human intestine. A new rapid and accurate method for detecting vitamin B12-intrinsic factor (IF-B12) receptors was used to study the distribution of mucosal IF-B12 receptors in three human small intestines. IF-B12 receptors in human intestine are present in significant amounts in the entire distal three-fifths of intestine. Triokinase activity is absent in the distal two-fifths of intestine, and tryptophan oxygenase is present only in the distal one-sixth, or most terminal part of the ileum. These data suggest (1) biochemical functions in the ileum have different anatomical distributions, (2) IF-B12 receptors correspond most closely with the accepted anatomical definitions of the ileum, and (3) vitamin B12 malabsorption seen in resection or disease of terminal ileum may not be attributable solely to a deficiency of ileal receptors."}
{"id": "PMID:198334", "title": "Esophageal function in diabetes mellitus and its relation to peripheral neuropathy.", "content": "Esophageal function was determined in 50 unselected patients with diabetes mellitus (DM). Fourteen age-matched healthy subjects served as controls. The presence of peripheral neuropathy (PN) was determined by a neurological examination and by nerve conduction studies. An intraluminal transducer assembly placed in the distal esophagus measured pressure in the lower esophageal sphincter and body of the esophagus. Esophageal function was studied both before and after edrophonium chloride, 80 microgram per kg intravenously. There was no significant difference in peristaltic amplitude between the controls and diabetics. There was also no difference in amplitude when DM was divided into presence or absence of PN. However, there was a significant decrease in velocity of peristalsis in DM with PN when compared to DM without PN and to controls. Resting lower esophageal sphincter pressure in DM was similar to controls, with no difference with or without PN. Twenty-eight patients (56%) with DM had abnormal motility, characterized by frequent spontaneous contractions, and decreased prevalence of peristalsis. Abnormal motility in DM was associated with PN and was characterized by a dysfunction of esophageal innervation with intact smooth muscle function.", "contents": "Esophageal function in diabetes mellitus and its relation to peripheral neuropathy. Esophageal function was determined in 50 unselected patients with diabetes mellitus (DM). Fourteen age-matched healthy subjects served as controls. The presence of peripheral neuropathy (PN) was determined by a neurological examination and by nerve conduction studies. An intraluminal transducer assembly placed in the distal esophagus measured pressure in the lower esophageal sphincter and body of the esophagus. Esophageal function was studied both before and after edrophonium chloride, 80 microgram per kg intravenously. There was no significant difference in peristaltic amplitude between the controls and diabetics. There was also no difference in amplitude when DM was divided into presence or absence of PN. However, there was a significant decrease in velocity of peristalsis in DM with PN when compared to DM without PN and to controls. Resting lower esophageal sphincter pressure in DM was similar to controls, with no difference with or without PN. Twenty-eight patients (56%) with DM had abnormal motility, characterized by frequent spontaneous contractions, and decreased prevalence of peristalsis. Abnormal motility in DM was associated with PN and was characterized by a dysfunction of esophageal innervation with intact smooth muscle function."}
{"id": "PMID:198344", "title": "[Effects of 5-(o-chlorophenyl)-1-methyl-7-nitro-1, 3-dihydro-2HO1, 4-benzodiazepin-2-one (ID-390) as compared to nitrazepam on the sleep-wakefulness cycle in cats (author's transl)].", "content": "ID-690 was given at doses over 0.3 mg/kg, and increase in state of arousal and decrease in state of slow wave sleep were observed. Nitrazepam at doses over 1.0 mg/kg revealed similar effects. These agents increased incidences of paradoxical sleep at a low dose of 0.03 mg/kg. When ID-690 was given at doses over 0.3 mg/kg, the number and duration of incidences of paradoxical sleep decreased. Nitrazepam at doses over 0.1 mg/kg had a similar depressive effect on paradoxical sleep. These results suggest that these benzodiazepines have, dose-dependently, both facilitative and depressive actions on paradoxical sleep, and that the dose of these agents which affects arousal is not always the same as that which affects paradoxical sleep.", "contents": "[Effects of 5-(o-chlorophenyl)-1-methyl-7-nitro-1, 3-dihydro-2HO1, 4-benzodiazepin-2-one (ID-390) as compared to nitrazepam on the sleep-wakefulness cycle in cats (author's transl)]. ID-690 was given at doses over 0.3 mg/kg, and increase in state of arousal and decrease in state of slow wave sleep were observed. Nitrazepam at doses over 1.0 mg/kg revealed similar effects. These agents increased incidences of paradoxical sleep at a low dose of 0.03 mg/kg. When ID-690 was given at doses over 0.3 mg/kg, the number and duration of incidences of paradoxical sleep decreased. Nitrazepam at doses over 0.1 mg/kg had a similar depressive effect on paradoxical sleep. These results suggest that these benzodiazepines have, dose-dependently, both facilitative and depressive actions on paradoxical sleep, and that the dose of these agents which affects arousal is not always the same as that which affects paradoxical sleep."}
{"id": "PMID:198345", "title": "[Skeletal changes in Down's syndrome. A correlation between radiological and cytogenetic findings (author's transl)].", "content": "One hundred and two patients with Down's syndrome aged one day to 17 years were examined radiologically, seven of these repeatedly. Films obtained included the chest in two planes, lateral spine, left hand and pelvis. The following features were noted; the number of paired ribs, ossification centres in the manubrium, height of lumbar vertebral bodies, shortening of the phalanges, bone age and calculation of the acetabula and ilial angle and ilial index. In all patients the chromosomes were examined in order to determine the cytogenetic type. The following features were found to be more common in Down's syndrome than in normals: abnormal ossification of the manubrium (33%), aplasia of the twelfth rib (18%), high lumbar vertebral bodies (50%), brachymesophalangia of the fifth ray (62%) and changes in skeletal maturation (acceleration or retardation in 48%). Changes in the pelvis were typical; with increasing age, the acetabular angle falls and the ilial angle increases. The most striking skeletal changes were found in 84 patients with trisomy 21.", "contents": "[Skeletal changes in Down's syndrome. A correlation between radiological and cytogenetic findings (author's transl)]. One hundred and two patients with Down's syndrome aged one day to 17 years were examined radiologically, seven of these repeatedly. Films obtained included the chest in two planes, lateral spine, left hand and pelvis. The following features were noted; the number of paired ribs, ossification centres in the manubrium, height of lumbar vertebral bodies, shortening of the phalanges, bone age and calculation of the acetabula and ilial angle and ilial index. In all patients the chromosomes were examined in order to determine the cytogenetic type. The following features were found to be more common in Down's syndrome than in normals: abnormal ossification of the manubrium (33%), aplasia of the twelfth rib (18%), high lumbar vertebral bodies (50%), brachymesophalangia of the fifth ray (62%) and changes in skeletal maturation (acceleration or retardation in 48%). Changes in the pelvis were typical; with increasing age, the acetabular angle falls and the ilial angle increases. The most striking skeletal changes were found in 84 patients with trisomy 21."}
{"id": "PMID:198346", "title": "[Problems of corticosteroid-induced adrenal insufficiency in surgery].", "content": "Patients previously treated with corticosteroids have a high risk whenever surgery is undertaken. Corticosteroid therapy, especially if prolonged, causes adrenal suppression. Therefore patients under steroid treatment need more, not less corticosteroids during the operative period.", "contents": "[Problems of corticosteroid-induced adrenal insufficiency in surgery]. Patients previously treated with corticosteroids have a high risk whenever surgery is undertaken. Corticosteroid therapy, especially if prolonged, causes adrenal suppression. Therefore patients under steroid treatment need more, not less corticosteroids during the operative period."}
{"id": "PMID:198347", "title": "[Dopaminergic Neurotransmission in Parkinson's syndrome (author's transl)].", "content": "More recent electrophysiological and biochemical data dealing with the functioning of the central dopaminergic synapse are reviewed in relationship to Parkinsonian symptomatology. Emphasis is put on the influence of feedback mechanisms involving pre and postsynaptic receptor sites, the dopaminergic-cholinergic imbalance and receptor supersentitivity. Stimulation of the dopamine-sensitive adenylatecyclase proved to be a good indicator of central dopaminergic receptor stimulation. Current therapeutic concepts are discussed in view of their limitations and side-effects.", "contents": "[Dopaminergic Neurotransmission in Parkinson's syndrome (author's transl)]. More recent electrophysiological and biochemical data dealing with the functioning of the central dopaminergic synapse are reviewed in relationship to Parkinsonian symptomatology. Emphasis is put on the influence of feedback mechanisms involving pre and postsynaptic receptor sites, the dopaminergic-cholinergic imbalance and receptor supersentitivity. Stimulation of the dopamine-sensitive adenylatecyclase proved to be a good indicator of central dopaminergic receptor stimulation. Current therapeutic concepts are discussed in view of their limitations and side-effects."}
{"id": "PMID:198348", "title": "Social work services for radiation therapy patients and their families.", "content": "A social worker helps meet the social and emotional needs of cancer patients undergoing radiation therapy at the University of Utah Medical Center and the needs of their families. He makes personal contact with the patient and family on their first visit to the radiation division, answers questions, provides information on community services, and generally lets the patient and family know that they can call on him any time during the treatment process. He also follows up patients who are still seriously ill after treatment, and tries to maintain periodic contact with families of patients who have died.", "contents": "Social work services for radiation therapy patients and their families. A social worker helps meet the social and emotional needs of cancer patients undergoing radiation therapy at the University of Utah Medical Center and the needs of their families. He makes personal contact with the patient and family on their first visit to the radiation division, answers questions, provides information on community services, and generally lets the patient and family know that they can call on him any time during the treatment process. He also follows up patients who are still seriously ill after treatment, and tries to maintain periodic contact with families of patients who have died."}
{"id": "PMID:198349", "title": "Gestational trophoblastic neoplasms: morphologic considerations.", "content": "Abnormal trophoblastic proliferation is the hallmark of a spectrum of lesions constituting the gestational trophoblastic neoplasms. Rapid proliferation, infiltration, vascular invasion, hematogenous dissemination, and spontaneous regression are features of both normal and neoplastic trophoblast. Trophoblastic hyperplasia without hydrops, hydatidiform mole, invasive mole, and gestational choriocarcinoma are related lesions, characterized by increasingly aberrant trophoblastic growth and worsening prognosis, if untreated. Difficulties in diagnosis may arise with respect to the normal early implantation site, the hydropic abortus, and postgestational, involuting, residual trophoblast. Histologic grading or hydatidiform moles is relevant to their prognosis and biologic behavior. Trophoblastic neoplasia may begin at any stage of pregnancy or puerperally with immediate or late and local or distant manifestations in the mother or the child. Cognizance of the capricius potential behavior of trophoblast permits successful management of its proliferative lesions, monitored by serial measurement of gonadotropin secretion.", "contents": "Gestational trophoblastic neoplasms: morphologic considerations. Abnormal trophoblastic proliferation is the hallmark of a spectrum of lesions constituting the gestational trophoblastic neoplasms. Rapid proliferation, infiltration, vascular invasion, hematogenous dissemination, and spontaneous regression are features of both normal and neoplastic trophoblast. Trophoblastic hyperplasia without hydrops, hydatidiform mole, invasive mole, and gestational choriocarcinoma are related lesions, characterized by increasingly aberrant trophoblastic growth and worsening prognosis, if untreated. Difficulties in diagnosis may arise with respect to the normal early implantation site, the hydropic abortus, and postgestational, involuting, residual trophoblast. Histologic grading or hydatidiform moles is relevant to their prognosis and biologic behavior. Trophoblastic neoplasia may begin at any stage of pregnancy or puerperally with immediate or late and local or distant manifestations in the mother or the child. Cognizance of the capricius potential behavior of trophoblast permits successful management of its proliferative lesions, monitored by serial measurement of gonadotropin secretion."}
{"id": "PMID:198350", "title": "Malignant germ cell tumors of the ovary.", "content": "This article reviews 281 malignant germ cell tumors of the ovary from the Armed Forces Institute of Pathology and highlights their distinctive clinical and pathologic features. Emphasis is placed on the importance of a combined therapeutic approach utilizing surgery, chemotherapy, and radiation. The rationale for unilateral salpingo-oophorectomy in conjunction with chemotherapy for certain types of neoplasm confined to one ovary (stage 1a) is emphasized, and the role of human chorionic gonadotropin and alpha-fetoprotein as tumor markers in the management of patients with these tumors is discussed.", "contents": "Malignant germ cell tumors of the ovary. This article reviews 281 malignant germ cell tumors of the ovary from the Armed Forces Institute of Pathology and highlights their distinctive clinical and pathologic features. Emphasis is placed on the importance of a combined therapeutic approach utilizing surgery, chemotherapy, and radiation. The rationale for unilateral salpingo-oophorectomy in conjunction with chemotherapy for certain types of neoplasm confined to one ovary (stage 1a) is emphasized, and the role of human chorionic gonadotropin and alpha-fetoprotein as tumor markers in the management of patients with these tumors is discussed."}
{"id": "PMID:198351", "title": "Functional ovarian tumors of stromal and sex cord origin.", "content": "Most functional ovarian tumors are of specific stromal or sex cord origin, capable of differentiating in either a female direction or, less commonly, a male direction. Tumors of stromal origin such as thecoma, stromal luteoma, and Leydig cell tumors are for all practical purposes benign, and evolve from mature ovarian stroma, recapitulating common non-neoplastic transformations such as stromal changes associated with follicle development and nodular stromal hyperplasia. Sex cord tumors of granulosa or Sertoli cell types are generally of a low order of malignancy, tending to late recurrence, occasional peritoneal seeding, and only rarely to distant metastasis. Nonfunctional tumors of the ovary may trigger hormone production from adjacent reactive stroma. Massive edema of the ovary due to partial torsion may simulate neoplasm and may produce hormonal syndromes by an unknown mechanism.", "contents": "Functional ovarian tumors of stromal and sex cord origin. Most functional ovarian tumors are of specific stromal or sex cord origin, capable of differentiating in either a female direction or, less commonly, a male direction. Tumors of stromal origin such as thecoma, stromal luteoma, and Leydig cell tumors are for all practical purposes benign, and evolve from mature ovarian stroma, recapitulating common non-neoplastic transformations such as stromal changes associated with follicle development and nodular stromal hyperplasia. Sex cord tumors of granulosa or Sertoli cell types are generally of a low order of malignancy, tending to late recurrence, occasional peritoneal seeding, and only rarely to distant metastasis. Nonfunctional tumors of the ovary may trigger hormone production from adjacent reactive stroma. Massive edema of the ovary due to partial torsion may simulate neoplasm and may produce hormonal syndromes by an unknown mechanism."}
{"id": "PMID:198352", "title": "The polymorphism of red cell uridine monophosphate kinase in two samples of the Italian population.", "content": "Red cell uridine monophosphate kinase polymorphism has been studied on a total of 915 individuals from two different areas of Italy (Milan and Rome). The two groups of about the same size show very similar gene frequencies. The UMPK2 allele in the pooled sample has a frequency of 2.8% which is significantly lower than those observed in the two other Caucasian populations so far examined.", "contents": "The polymorphism of red cell uridine monophosphate kinase in two samples of the Italian population. Red cell uridine monophosphate kinase polymorphism has been studied on a total of 915 individuals from two different areas of Italy (Milan and Rome). The two groups of about the same size show very similar gene frequencies. The UMPK2 allele in the pooled sample has a frequency of 2.8% which is significantly lower than those observed in the two other Caucasian populations so far examined."}
{"id": "PMID:198353", "title": "An analysis of red cell enzymatic markers in the province of Bologna (Italy).", "content": "About 280 unrelated individuals living in the province of Bologna (Northern Italy) have been studied for the following red cell enzymatic markers: phosphoglucomutase (PGM), adenylate kinase (AK), adenosine deaminase (ADA) and phosphohexose isomerase (PHI). 116 subjects from the same sample have also been analysed for red cell acid phosphatase (ACP). The observed gene frequencies are PGM21 = 0.280; AK2 = 0.030; ADA2 = 0.091; ACPa = 0.297; ACPb = 0.647; ACPc = 0.056. In the PHI system two individuals with the variant PHI 3-1 phenotype have been found.", "contents": "An analysis of red cell enzymatic markers in the province of Bologna (Italy). About 280 unrelated individuals living in the province of Bologna (Northern Italy) have been studied for the following red cell enzymatic markers: phosphoglucomutase (PGM), adenylate kinase (AK), adenosine deaminase (ADA) and phosphohexose isomerase (PHI). 116 subjects from the same sample have also been analysed for red cell acid phosphatase (ACP). The observed gene frequencies are PGM21 = 0.280; AK2 = 0.030; ADA2 = 0.091; ACPa = 0.297; ACPb = 0.647; ACPc = 0.056. In the PHI system two individuals with the variant PHI 3-1 phenotype have been found."}
{"id": "PMID:198354", "title": "Enzyme polymorphisms of Ideles populations (Ahaggar, Algeria) and the Iwellemeden Kel Kummer Twaregs (Menaka, Mali).", "content": "Surveys dealing with enzyme polymorphisms have recently been conducted in the Sahara. Results from two populations are reported here: 227 inhabitants of Ideles village (Ahaggar, Algeria); 285 nomads of a genetic isolate, the Kel Kummer Twareg tribe (Menaka, Mali). The four classical molecular variants of G6PD:A+, A-, B+, B-, are found in Ideles. The frequency of the G6PD A+ Negroid variant reaches 15% in Ideles and 7.7% among the Kel Kummer. However, gene frequencies will have to be recalculated after a study of the genetic transmission through families. The PGDC gene of 6PGD is especially frequent in the Kel Kummer where 10 'Canning' phenotypes have been observed. The PGM distribution of alleles at locus 1 in Ideles is the same as in the Mediterranean populations. The pa gene of acid phosphatase, relatively frequent in Ideles, has been excluded by drift from the Kel Kummer gene pool. AK and LDH enzymes have also been studied in both samples. The abnormal Ea1 mutation of serum pseudocholinesterase exists in Ideles and in the Kel Kummer as in other populations of the Sahara; the C5 esterase component was revealed by electrophoresis in 5% of the Kel Kummer people.", "contents": "Enzyme polymorphisms of Ideles populations (Ahaggar, Algeria) and the Iwellemeden Kel Kummer Twaregs (Menaka, Mali). Surveys dealing with enzyme polymorphisms have recently been conducted in the Sahara. Results from two populations are reported here: 227 inhabitants of Ideles village (Ahaggar, Algeria); 285 nomads of a genetic isolate, the Kel Kummer Twareg tribe (Menaka, Mali). The four classical molecular variants of G6PD:A+, A-, B+, B-, are found in Ideles. The frequency of the G6PD A+ Negroid variant reaches 15% in Ideles and 7.7% among the Kel Kummer. However, gene frequencies will have to be recalculated after a study of the genetic transmission through families. The PGDC gene of 6PGD is especially frequent in the Kel Kummer where 10 'Canning' phenotypes have been observed. The PGM distribution of alleles at locus 1 in Ideles is the same as in the Mediterranean populations. The pa gene of acid phosphatase, relatively frequent in Ideles, has been excluded by drift from the Kel Kummer gene pool. AK and LDH enzymes have also been studied in both samples. The abnormal Ea1 mutation of serum pseudocholinesterase exists in Ideles and in the Kel Kummer as in other populations of the Sahara; the C5 esterase component was revealed by electrophoresis in 5% of the Kel Kummer people."}
{"id": "PMID:198355", "title": "Adenylate cyclase activity in cultured epithelial cells.", "content": "The cyclic AMP metabolism of cultured epithelial cells was investigated. Epinephrine or 1-methyl,3-isobutylxanthine (MIX) alone had no effect on cyclic AMP levels in intact cells, whereas the combination of the two agents yielded a 6- to 10-fold increase in cyclic AMP levels. Both basal and stimulated cyclic AMP levels decreased with increasing cell density. Cell-free adenylate cyclase preparations were stimulated markedly by epinephrine or isoproterenol in the absence of MIX. Since the epithelial cells were found to have a relatively small amount of cyclic nucleotide phosphodiesterase (PDE) activity, the requirement for MIX to visualize intact cell responsiveness to epinephrine could be explained only partially by its PDE inhibitory properties.", "contents": "Adenylate cyclase activity in cultured epithelial cells. The cyclic AMP metabolism of cultured epithelial cells was investigated. Epinephrine or 1-methyl,3-isobutylxanthine (MIX) alone had no effect on cyclic AMP levels in intact cells, whereas the combination of the two agents yielded a 6- to 10-fold increase in cyclic AMP levels. Both basal and stimulated cyclic AMP levels decreased with increasing cell density. Cell-free adenylate cyclase preparations were stimulated markedly by epinephrine or isoproterenol in the absence of MIX. Since the epithelial cells were found to have a relatively small amount of cyclic nucleotide phosphodiesterase (PDE) activity, the requirement for MIX to visualize intact cell responsiveness to epinephrine could be explained only partially by its PDE inhibitory properties."}
{"id": "PMID:198356", "title": "A further study on the regulation of cyclic nucleotide phosphodiesterase activity in neuroblastoma cells: effect of growth.", "content": "Adenosine 3',5'-cyclic monophosphate (cyclic AMP) phsophodiesterase activity in mouse neuroblastoma cells in culture markedly increased during exponential growth and reached a maximal level at confluency; whereas guanosine 3'5'-cyclic monophosphate (cyclic GMP) phosphodiesterase activity only slightly but significantly increased under a similar experimental condition. The increase in cyclic AMP phosphodiesterase activity was blocked by both cycloheximide and dactinomycin, whereas the increase in cyclic GMP phosphodiesterase was blocked by only cycloheximide. When the confluent cells were replated at low density, the cyclic nucleotide phosphodiesterase activity decreased; however, when they were plated at high cell density which equaled confluency, the enzyme activity did not decrease. Unlike cyclic AMP phosphodiesterase activity, cyclic GMP phosphodiesterase activity did not change significantly in prostaglandin E1-treated cells, but decreased in cells treated with the inhibitor of phosphodiesterase. Like cyclic AMP phosphodiesterase activity, cyclic GMP phosphodiesterase activity also did not change in cells treated with serum-free medium, X-irradiation, sodium butyrate and 6-thioguanine.", "contents": "A further study on the regulation of cyclic nucleotide phosphodiesterase activity in neuroblastoma cells: effect of growth. Adenosine 3',5'-cyclic monophosphate (cyclic AMP) phsophodiesterase activity in mouse neuroblastoma cells in culture markedly increased during exponential growth and reached a maximal level at confluency; whereas guanosine 3'5'-cyclic monophosphate (cyclic GMP) phosphodiesterase activity only slightly but significantly increased under a similar experimental condition. The increase in cyclic AMP phosphodiesterase activity was blocked by both cycloheximide and dactinomycin, whereas the increase in cyclic GMP phosphodiesterase was blocked by only cycloheximide. When the confluent cells were replated at low density, the cyclic nucleotide phosphodiesterase activity decreased; however, when they were plated at high cell density which equaled confluency, the enzyme activity did not decrease. Unlike cyclic AMP phosphodiesterase activity, cyclic GMP phosphodiesterase activity did not change significantly in prostaglandin E1-treated cells, but decreased in cells treated with the inhibitor of phosphodiesterase. Like cyclic AMP phosphodiesterase activity, cyclic GMP phosphodiesterase activity also did not change in cells treated with serum-free medium, X-irradiation, sodium butyrate and 6-thioguanine."}
{"id": "PMID:198357", "title": "Interferon inhibition of lymphocyte mitogenesis.", "content": "Interferon inhibits the early phase of mitogenic action of Concanavalin A on lymphocytes as measured by incorporation of labelled precursors in RNA, DNA or protein. There was no evidence for a role of cyclic AMP in the process of inhibition. Dialysis of interferon against high salt and urea did not separate cell inhibitory activity from antiviral activity. Thus, these results are compatible with the possibility that the antiviral and cell inhibitory activities are in the same molecule. However, further purification of the interferon will be required to verify this assumption.", "contents": "Interferon inhibition of lymphocyte mitogenesis. Interferon inhibits the early phase of mitogenic action of Concanavalin A on lymphocytes as measured by incorporation of labelled precursors in RNA, DNA or protein. There was no evidence for a role of cyclic AMP in the process of inhibition. Dialysis of interferon against high salt and urea did not separate cell inhibitory activity from antiviral activity. Thus, these results are compatible with the possibility that the antiviral and cell inhibitory activities are in the same molecule. However, further purification of the interferon will be required to verify this assumption."}
{"id": "PMID:198358", "title": "Effects of whole-body irradiation on antibody affinity.", "content": "Mice exposed to a sublethal dose of X-rays were immunized with alum-precipitated DNP-KLH (dinitrophenyl-keyhole limpet haemocyanin) and B. pertussis either before or after irradiation. The primary anti-DNP antibody response was evaluated during 8 weeks after immunization by the equilibrium dialysis technique using ammonium sulphate- precipitated serum globulins and the ligand 3H-labelled xi-DNP-L-Lysine. The serum concentrations of antibody sites in mice immunized 1-5 days before or 2 h-8 weeks after 450 rad were below the values in unirradiated controls at all bleeding times. Antibody affinity, however, was found to be up to 20 fold higher in irradiated mice than in control mice when antigen was injected before, or 3-8 weeks after, irradiation. Spleen cells from mice exposed to 450 rad 1-9 weeks before killing were stimulated in vitro with PHA, ConA, or LPS. Recovery profiles of mitotic responsiveness suggest that enhancement of antibody affinity in irradiated mice could result from relative lack of suppressor T Cells.", "contents": "Effects of whole-body irradiation on antibody affinity. Mice exposed to a sublethal dose of X-rays were immunized with alum-precipitated DNP-KLH (dinitrophenyl-keyhole limpet haemocyanin) and B. pertussis either before or after irradiation. The primary anti-DNP antibody response was evaluated during 8 weeks after immunization by the equilibrium dialysis technique using ammonium sulphate- precipitated serum globulins and the ligand 3H-labelled xi-DNP-L-Lysine. The serum concentrations of antibody sites in mice immunized 1-5 days before or 2 h-8 weeks after 450 rad were below the values in unirradiated controls at all bleeding times. Antibody affinity, however, was found to be up to 20 fold higher in irradiated mice than in control mice when antigen was injected before, or 3-8 weeks after, irradiation. Spleen cells from mice exposed to 450 rad 1-9 weeks before killing were stimulated in vitro with PHA, ConA, or LPS. Recovery profiles of mitotic responsiveness suggest that enhancement of antibody affinity in irradiated mice could result from relative lack of suppressor T Cells."}
{"id": "PMID:198359", "title": "Action of sphingomyelinase C and other lipid-specific agents as inhibitors of Fc binding and locomotion in human leucocytes.", "content": "The binding of antibody-coated chicken erythrocytes (EA) to human blood lymphocytes and monocytes is inhibited by pretreatment of the leucocytes with sphingomyelinase C. Inhibition of rosetting of neuraminidase-treated EA with neutrophils is also seen with this enzyme. The cholesterol-binding theta-toxin of Clostridium perfringens and pronase also inhibit EA-rosette formation, but less strongly than sphingomyelinase. The lipid-specific agents also inhibit chemotactic migration of leucocytes to casein and denatured HSA, whereas proteases and glycosidases do not. These results suggest that membrane lipids are important constituents of the binding sites for Fc fragments and for certain chemotactic factors and point to an important role for sphingomyelin in this binding.", "contents": "Action of sphingomyelinase C and other lipid-specific agents as inhibitors of Fc binding and locomotion in human leucocytes. The binding of antibody-coated chicken erythrocytes (EA) to human blood lymphocytes and monocytes is inhibited by pretreatment of the leucocytes with sphingomyelinase C. Inhibition of rosetting of neuraminidase-treated EA with neutrophils is also seen with this enzyme. The cholesterol-binding theta-toxin of Clostridium perfringens and pronase also inhibit EA-rosette formation, but less strongly than sphingomyelinase. The lipid-specific agents also inhibit chemotactic migration of leucocytes to casein and denatured HSA, whereas proteases and glycosidases do not. These results suggest that membrane lipids are important constituents of the binding sites for Fc fragments and for certain chemotactic factors and point to an important role for sphingomyelin in this binding."}
{"id": "PMID:198363", "title": "The effects of inhaled silica and chrysotile on the elastic properties of rat lungs; physiological, physical and biochemical studies of lung surfactant.", "content": "When rats breathed air containing approximately 70 mg m-3 of respirable crystalline silica 7 h daily for 10 days (2000 mg m-3 h) the surface tension forces of the alveolar lining film were reduced. This was shown both by surface tension measurements on lung extracts and by pressure-volume studies with air and saline filling of excised lungs. Larger quantities of inhaled silica produced similar effects. Chrysotile inhalation caused an even more marked decrease in the surface tension forces. In the chrysotile studies these findings were supported by biochemical estimations of the quantity of surfactant in the lungs, which was increased 10-fold by an inhalation of 6500 mg m-3 h. Electron microscopy showed an increased number of the type II alveolar cells which produce surfactant and of free phospholipid lattices in the air spaces of the lungs of rats exposed to chrysotile and silica. Both the surface tension and biochemical estimations on a control group of rats suggest that there is an increase in the amount of surfactant in the lungs up to about 12 months of age.", "contents": "The effects of inhaled silica and chrysotile on the elastic properties of rat lungs; physiological, physical and biochemical studies of lung surfactant. When rats breathed air containing approximately 70 mg m-3 of respirable crystalline silica 7 h daily for 10 days (2000 mg m-3 h) the surface tension forces of the alveolar lining film were reduced. This was shown both by surface tension measurements on lung extracts and by pressure-volume studies with air and saline filling of excised lungs. Larger quantities of inhaled silica produced similar effects. Chrysotile inhalation caused an even more marked decrease in the surface tension forces. In the chrysotile studies these findings were supported by biochemical estimations of the quantity of surfactant in the lungs, which was increased 10-fold by an inhalation of 6500 mg m-3 h. Electron microscopy showed an increased number of the type II alveolar cells which produce surfactant and of free phospholipid lattices in the air spaces of the lungs of rats exposed to chrysotile and silica. Both the surface tension and biochemical estimations on a control group of rats suggest that there is an increase in the amount of surfactant in the lungs up to about 12 months of age."}
{"id": "PMID:198364", "title": "A cell kinetic study of the alveolar wall following dust deposition.", "content": "The stathmokinetic technique was used to study quantitatively the proliferative response of cells comprising the alveolar wall of inbred mice which had inhaled coal or quartz. The exposures occupied 4 weeks and the observations continued over an extended period thereafter. Control observations suggested that mitotic inhibition was induced solely by residence in the exposure chamber, since cessation of exposure was quickly followed by a temporary rise of proliferative activity. This feature was not apparent when dust was inhaled, though with comparable exposure to both coal and quartz there was an elevation in mitotoic incidence of alveolar wall cells in dust-free areas of lung at a later interval. In dust-laden areas the rise was less in evidence, a situation that persisted throughout the post-exposure survival. The difference in mitotic incidence between dust-free and dust-containing areas was more evident after coal than after quartz inhalation, whilst in higher concentration a quartz aerosol induced a continued depression of mitotic activity. The proliferative response seen in the alveolar walls of control and dusted mice is most likely to be contributed by the interstitial precursors of alveolar macrophages, cells which are recognized to be marrow derived. The changes observed in mitotic incidence are interpreted in terms of demand for alveolar macrophages according to the nature of the dust and the inintensity of the exposure.", "contents": "A cell kinetic study of the alveolar wall following dust deposition. The stathmokinetic technique was used to study quantitatively the proliferative response of cells comprising the alveolar wall of inbred mice which had inhaled coal or quartz. The exposures occupied 4 weeks and the observations continued over an extended period thereafter. Control observations suggested that mitotic inhibition was induced solely by residence in the exposure chamber, since cessation of exposure was quickly followed by a temporary rise of proliferative activity. This feature was not apparent when dust was inhaled, though with comparable exposure to both coal and quartz there was an elevation in mitotoic incidence of alveolar wall cells in dust-free areas of lung at a later interval. In dust-laden areas the rise was less in evidence, a situation that persisted throughout the post-exposure survival. The difference in mitotic incidence between dust-free and dust-containing areas was more evident after coal than after quartz inhalation, whilst in higher concentration a quartz aerosol induced a continued depression of mitotic activity. The proliferative response seen in the alveolar walls of control and dusted mice is most likely to be contributed by the interstitial precursors of alveolar macrophages, cells which are recognized to be marrow derived. The changes observed in mitotic incidence are interpreted in terms of demand for alveolar macrophages according to the nature of the dust and the inintensity of the exposure."}
{"id": "PMID:198365", "title": "The activation of phospholipase A in macrophages after the phagocytosis of silica and other cytotoxic dusts.", "content": "The phospholipid and lipid metabolism of mouse peritoneal macrophages has been studied in the presence of various silicogenic dusts and asbestos particles. These extensive kinetic studies were possible as a reproducible method was developed to determine these major cellular constituents after labelling macrophages with 1-14C-oleic acid. The following results have been obtained so far: 1. Silicogenic dusts activate a phospholipase A in macrophages leading to a concentration and time-dependent degradation of lecithin and cephalin. 2. Using low doses of SiO2 (less than 1 mg/10(7) cells) the split-off free fatty acid can still be transesterified into the triglycerides. 3. High doses of silica (greater than 2 mg/10(7) cells) induce also a lipolysis. 4. Silica specifically inhibits a plasma membrane-bound acyltransferase 5. Asbestos particles induce in long-term cultures a moderate degradation of diacylphospholipids with transesterification of 1-14C-oleic acid into the triglycerides.", "contents": "The activation of phospholipase A in macrophages after the phagocytosis of silica and other cytotoxic dusts. The phospholipid and lipid metabolism of mouse peritoneal macrophages has been studied in the presence of various silicogenic dusts and asbestos particles. These extensive kinetic studies were possible as a reproducible method was developed to determine these major cellular constituents after labelling macrophages with 1-14C-oleic acid. The following results have been obtained so far: 1. Silicogenic dusts activate a phospholipase A in macrophages leading to a concentration and time-dependent degradation of lecithin and cephalin. 2. Using low doses of SiO2 (less than 1 mg/10(7) cells) the split-off free fatty acid can still be transesterified into the triglycerides. 3. High doses of silica (greater than 2 mg/10(7) cells) induce also a lipolysis. 4. Silica specifically inhibits a plasma membrane-bound acyltransferase 5. Asbestos particles induce in long-term cultures a moderate degradation of diacylphospholipids with transesterification of 1-14C-oleic acid into the triglycerides."}
{"id": "PMID:198366", "title": "Comparative pulmonary carcinogenicity of inhaled beta-emitting radionuclides in beagle dogs.", "content": "Beta-emitting radionuclides are important constituents of isotope inventories in light water reactors and may pose an inhalation hazard to industrial workers or the general population if they are released. To study the biological effects of such potential exposures, a series of life span studies was initiated in which beagle dogs were exposed to aerosols of relatively insoluble fused clay particles containing 90Y, 91Y, 144Ce or 90Sr. Groups of dogs exposed to each radionuclide received graded initial lung burdens of radioactivity. When combined with the varied physical half-lives of the four radionuclides, this resulted in a wide variety of radiation doses and dose patterns to the lung. Deaths (greater than 640 days after exposure) were generally associated with pulmonary neoplasia in dogs that inhaled 91Y, 144Ce or 90Sr. These dogs had cumulative lung doses to death greater than 20 000 rads. Exposure to 144Ce or 90Sr with dose rates that decreased slowly induced pulmonary haemangiosarcomas. Pulmonary irradiation from 91Y, with a rapidly decreasing dose rate, resulted in pulmonary epithelial tumours. No malignant lung tumours have been seen within 1540 days after exposure to 90Y. The animals in the main studies have been observed for 1342 to 2756 days after exposure.", "contents": "Comparative pulmonary carcinogenicity of inhaled beta-emitting radionuclides in beagle dogs. Beta-emitting radionuclides are important constituents of isotope inventories in light water reactors and may pose an inhalation hazard to industrial workers or the general population if they are released. To study the biological effects of such potential exposures, a series of life span studies was initiated in which beagle dogs were exposed to aerosols of relatively insoluble fused clay particles containing 90Y, 91Y, 144Ce or 90Sr. Groups of dogs exposed to each radionuclide received graded initial lung burdens of radioactivity. When combined with the varied physical half-lives of the four radionuclides, this resulted in a wide variety of radiation doses and dose patterns to the lung. Deaths (greater than 640 days after exposure) were generally associated with pulmonary neoplasia in dogs that inhaled 91Y, 144Ce or 90Sr. These dogs had cumulative lung doses to death greater than 20 000 rads. Exposure to 144Ce or 90Sr with dose rates that decreased slowly induced pulmonary haemangiosarcomas. Pulmonary irradiation from 91Y, with a rapidly decreasing dose rate, resulted in pulmonary epithelial tumours. No malignant lung tumours have been seen within 1540 days after exposure to 90Y. The animals in the main studies have been observed for 1342 to 2756 days after exposure."}
{"id": "PMID:198368", "title": "The effect of quartz and other non-coal dusts in coalworkers' pneumoconiosis. Part II. Lung autopsy study.", "content": "Preliminary pathological and mineralogical studies are reported on seventy-four sets of lungs from British coal miners who have been employed at the collieries included in the National Coal Boards's Pneumoconiosis Field Research. The degree of lung damage was considered in relation to the lung dust content and to the known dust exposures of the men concerned. Lungs were classified as having soft macules, fibrotic nodules or PMF. Those with soft macules had the lowest dust content but there was no significant difference between the dust contents of the lungs with fibrotic lesions and those with PMF. The percentage of non-coal minerals in the lung dust appeared to increase with the pathological classification from soft macules to PMF, and comparisons with the exposure data indicated a preferential retention of non-coal minerals, and especially of quartz, in the cases with the more severe lesions. Histological examination of the lesions showed the packing of dust was less close and the cellular response more vigorous with the lungs with the highest quartz content.", "contents": "The effect of quartz and other non-coal dusts in coalworkers' pneumoconiosis. Part II. Lung autopsy study. Preliminary pathological and mineralogical studies are reported on seventy-four sets of lungs from British coal miners who have been employed at the collieries included in the National Coal Boards's Pneumoconiosis Field Research. The degree of lung damage was considered in relation to the lung dust content and to the known dust exposures of the men concerned. Lungs were classified as having soft macules, fibrotic nodules or PMF. Those with soft macules had the lowest dust content but there was no significant difference between the dust contents of the lungs with fibrotic lesions and those with PMF. The percentage of non-coal minerals in the lung dust appeared to increase with the pathological classification from soft macules to PMF, and comparisons with the exposure data indicated a preferential retention of non-coal minerals, and especially of quartz, in the cases with the more severe lesions. Histological examination of the lesions showed the packing of dust was less close and the cellular response more vigorous with the lungs with the highest quartz content."}
{"id": "PMID:198369", "title": "Characteristics of lung dusts and their relation to dust exposure and pathological findings in the lungs.", "content": "Lung dusts were investigated, post-mortem, in twenty-five miners from mixed metal mines, tunnels, and quarries who had exposed to high concentrations of mixed dust containing about 20-25% free crystalline silica. The character of the relations found between the amount of quartz per 100 g dry tissue and the clinical, X-ray and pathological findings is similar to that established in coal miners. The difference lies in the fact that with equal amounts of quartz per 100 g dry tissue, there is less silicosis in coal miners than in our cases; the average residence time of retained dust is longer in coal miners, but its quartz per cent is lower.", "contents": "Characteristics of lung dusts and their relation to dust exposure and pathological findings in the lungs. Lung dusts were investigated, post-mortem, in twenty-five miners from mixed metal mines, tunnels, and quarries who had exposed to high concentrations of mixed dust containing about 20-25% free crystalline silica. The character of the relations found between the amount of quartz per 100 g dry tissue and the clinical, X-ray and pathological findings is similar to that established in coal miners. The difference lies in the fact that with equal amounts of quartz per 100 g dry tissue, there is less silicosis in coal miners than in our cases; the average residence time of retained dust is longer in coal miners, but its quartz per cent is lower."}
{"id": "PMID:198370", "title": "Immunoglobulin class-specific antibody response in serum, spleen, lungs, and bronchoalveolar washings after primary and secondary sendai virus infection of germfree mice.", "content": "Immunoglobulin class-specific antibodies were measured by a solid-phase radioimmunoassay in serum, bronchoalveolar washings (BAW), lung cell lysates, and spleen cell lysates in germfree mice after intranasal (i.n.) and intraperitoneal (i.p.) primary and secondary 10(5), 10(4), and 10(3) mean tissue culture infective doses (TCID(50)) of live parainfluenza 1 (Sendai) virus. The earliest antibody detected in lungs after i.n. virus challenge was immunoglobulin G (IgG), followed by IgM and, lastly, IgA. The local IgA response after both primary and secondary i.n. virus challenge was lowest after the severest infection. It is suggested that the delayed appearance of IgA antibody and the lower response after severe lung damage may be related to a temporary local secretory component-producing cell deficiency. The lungs were a major source of serum IgG antibody after both primary and secondary i.n. virus challenge. Only IgG and IgM antibodies were detectable in lung cell lysates after the i.n. 10(3) TCID(50) secondary response. A secondary response was detected in IgG, IgA, and IgM after secondary i.n. challenge with the other two doses. The lung response to all of primary and secondary i.p. doses of virus was exclusively IgG and IgM. Calculation of radioimmunoassay antibody per microgram of IgG, IgA, and IgM in serum and BAW after both i.n. and i.p. virus challenges showed that, when BAW antibody was present, the ratio in BAW was always higher than that in serum. This finding in the i.n. mice, together with the presence of IgA antibody-containing cells in the lungs, strongly indicates local manufacture and secretion of IgA antibodies in these animals and suggests that the same conclusion could apply to local IgG and IgM antibodies after both i.n. and i.p. challenges.", "contents": "Immunoglobulin class-specific antibody response in serum, spleen, lungs, and bronchoalveolar washings after primary and secondary sendai virus infection of germfree mice. Immunoglobulin class-specific antibodies were measured by a solid-phase radioimmunoassay in serum, bronchoalveolar washings (BAW), lung cell lysates, and spleen cell lysates in germfree mice after intranasal (i.n.) and intraperitoneal (i.p.) primary and secondary 10(5), 10(4), and 10(3) mean tissue culture infective doses (TCID(50)) of live parainfluenza 1 (Sendai) virus. The earliest antibody detected in lungs after i.n. virus challenge was immunoglobulin G (IgG), followed by IgM and, lastly, IgA. The local IgA response after both primary and secondary i.n. virus challenge was lowest after the severest infection. It is suggested that the delayed appearance of IgA antibody and the lower response after severe lung damage may be related to a temporary local secretory component-producing cell deficiency. The lungs were a major source of serum IgG antibody after both primary and secondary i.n. virus challenge. Only IgG and IgM antibodies were detectable in lung cell lysates after the i.n. 10(3) TCID(50) secondary response. A secondary response was detected in IgG, IgA, and IgM after secondary i.n. challenge with the other two doses. The lung response to all of primary and secondary i.p. doses of virus was exclusively IgG and IgM. Calculation of radioimmunoassay antibody per microgram of IgG, IgA, and IgM in serum and BAW after both i.n. and i.p. virus challenges showed that, when BAW antibody was present, the ratio in BAW was always higher than that in serum. This finding in the i.n. mice, together with the presence of IgA antibody-containing cells in the lungs, strongly indicates local manufacture and secretion of IgA antibodies in these animals and suggests that the same conclusion could apply to local IgG and IgM antibodies after both i.n. and i.p. challenges."}
{"id": "PMID:198371", "title": "Antigenic relationship between human and bovine rotaviruses as determined by neutralization, immune adherence hemagglutination, and complement fixation tests.", "content": "Guinea pig antiserum to bovine rotavirus does not neutralize human rotavirus. Bovine and human rotaviruses were, however, extensively cross-reactive when examined by complement fixation and immune adherence hemagglutination tests with antiserum to either virus. The immune adherence hemagglutination test was 16- to 32-fold more sensitive than the complement fixation test in detecting rotavirus.", "contents": "Antigenic relationship between human and bovine rotaviruses as determined by neutralization, immune adherence hemagglutination, and complement fixation tests. Guinea pig antiserum to bovine rotavirus does not neutralize human rotavirus. Bovine and human rotaviruses were, however, extensively cross-reactive when examined by complement fixation and immune adherence hemagglutination tests with antiserum to either virus. The immune adherence hemagglutination test was 16- to 32-fold more sensitive than the complement fixation test in detecting rotavirus."}
{"id": "PMID:198372", "title": "Sequential changes in cell-mediated immune responses to herpes simplex virus after recurrent herpetic infection in humans.", "content": "Lymphocyte responses to herpes simplex virus (HSV) were studied in 23 patients with recurrent herpes labialis and in 19 control subjects. Lymphocytes of seropositive, but not seronegative, controls responded to HSV by thymidine incorporation, and the supernatant fluids inhibited the migration of guinea pig macrophages. Lymphocytes from patients with a recurrent herpetic lesion responded to HSV by significantly greater thymidine incorporation than seropositive controls, but supernatants did not show an increased macrophage migration inhibition response. During the 28 days after the onset of a lesion, the thymidine incorporation to HSV fell to the level of the seropositive controls, and supernatants then induced an increased inhibition of macrophage migration. Lymphocyte responses to Candida albicans, purified protein derivative, or phytohemagglutinin did not fluctuate according to the presence of a lesion and did not differ from those of the controls. Lymphocyte responses to HSV were unaffected by culture in the presence of serum from seronegative or seropositive controls, or from patients with or without a herpetic lesion. It is suggested that in patients with recurrent herpes labialis a periodic defect of the migration inhibition response might have allowed the recurrent infection to develop, and that the increased thymidine incorporation stimulated by HSV in vitro is a result of antigenic stimulation from the lesion.", "contents": "Sequential changes in cell-mediated immune responses to herpes simplex virus after recurrent herpetic infection in humans. Lymphocyte responses to herpes simplex virus (HSV) were studied in 23 patients with recurrent herpes labialis and in 19 control subjects. Lymphocytes of seropositive, but not seronegative, controls responded to HSV by thymidine incorporation, and the supernatant fluids inhibited the migration of guinea pig macrophages. Lymphocytes from patients with a recurrent herpetic lesion responded to HSV by significantly greater thymidine incorporation than seropositive controls, but supernatants did not show an increased macrophage migration inhibition response. During the 28 days after the onset of a lesion, the thymidine incorporation to HSV fell to the level of the seropositive controls, and supernatants then induced an increased inhibition of macrophage migration. Lymphocyte responses to Candida albicans, purified protein derivative, or phytohemagglutinin did not fluctuate according to the presence of a lesion and did not differ from those of the controls. Lymphocyte responses to HSV were unaffected by culture in the presence of serum from seronegative or seropositive controls, or from patients with or without a herpetic lesion. It is suggested that in patients with recurrent herpes labialis a periodic defect of the migration inhibition response might have allowed the recurrent infection to develop, and that the increased thymidine incorporation stimulated by HSV in vitro is a result of antigenic stimulation from the lesion."}
{"id": "PMID:198373", "title": "Transplacental transmission of polyoma virus in mice.", "content": "When pregnant mice were inoculated on day 1 of gestation with polyoma, some of them exhibited total resorption or reduced litter size, the extent depending on the dose of virus. Virus was detected in 4 out of 11 mouse embryo fibroblast (MEF) cultures made from infected mothers. After maternal infection on day 5 or 10 of gestation, virus titers of up to 10(7) 50% tissue culture infectious doses (TCID50)/g of fetus were found in all pools of fetuses tested 5 days later, with the titers falling by day 6. Hemagglutination-inhibiting antibodies against polyoma appeared in maternal serum by day 6 and rose to a maximum by day 14. Immunoglobulin G class antibodies were detected by day 7, with titers rising rapidly to a maximum at day 14. After maternal infection later in gestation (day 15), one out of three litters of newborn mice was found to have 10(5) TCID50 polyoma virus per g in pooled kidney samples.", "contents": "Transplacental transmission of polyoma virus in mice. When pregnant mice were inoculated on day 1 of gestation with polyoma, some of them exhibited total resorption or reduced litter size, the extent depending on the dose of virus. Virus was detected in 4 out of 11 mouse embryo fibroblast (MEF) cultures made from infected mothers. After maternal infection on day 5 or 10 of gestation, virus titers of up to 10(7) 50% tissue culture infectious doses (TCID50)/g of fetus were found in all pools of fetuses tested 5 days later, with the titers falling by day 6. Hemagglutination-inhibiting antibodies against polyoma appeared in maternal serum by day 6 and rose to a maximum by day 14. Immunoglobulin G class antibodies were detected by day 7, with titers rising rapidly to a maximum at day 14. After maternal infection later in gestation (day 15), one out of three litters of newborn mice was found to have 10(5) TCID50 polyoma virus per g in pooled kidney samples."}
{"id": "PMID:198374", "title": "Heterogeneity of the sensitivity of vesicular stomatitis virus to interferons.", "content": "Twelve cloned viruses were randomly isolated from original (uncloned) vesicular stomatitis virus (VSV), and their sensitivities to mouse and human interferons were examined. When the interferon sensitivities of these various VSVs were compared by the plaque reduction method in L cells, virus 3 was found to be sevenfold more sensitive than virus 11, and the interferon sensitivity of the original (uncloned) virus was intermediate. The present study shows that uncloned VSV Indiana strain is a mixture of viruses that have different sensitivities to interferon. The slope of the dose-response curve of original (uncloned) virus to mouse interferon was less steep than those of cloned viruses. Virus 11, which was the least sensitive to mouse interferon, was relatively sensitive to human interferon. There was no correlation between the sensitivities of virus clones to mouse interferon and their sensitivities to human interferon. When the interferon sensitivities were tested by various assay methods (plaque reduction, yield reduction, and cytopathic effect inhibition), the ranking of the interferon sensitivities of different viruses was not changed. These results indicate that the relative sensitivity of a virus to interferon is determined by the host cells in which the tests are performed, but not by assay method used.", "contents": "Heterogeneity of the sensitivity of vesicular stomatitis virus to interferons. Twelve cloned viruses were randomly isolated from original (uncloned) vesicular stomatitis virus (VSV), and their sensitivities to mouse and human interferons were examined. When the interferon sensitivities of these various VSVs were compared by the plaque reduction method in L cells, virus 3 was found to be sevenfold more sensitive than virus 11, and the interferon sensitivity of the original (uncloned) virus was intermediate. The present study shows that uncloned VSV Indiana strain is a mixture of viruses that have different sensitivities to interferon. The slope of the dose-response curve of original (uncloned) virus to mouse interferon was less steep than those of cloned viruses. Virus 11, which was the least sensitive to mouse interferon, was relatively sensitive to human interferon. There was no correlation between the sensitivities of virus clones to mouse interferon and their sensitivities to human interferon. When the interferon sensitivities were tested by various assay methods (plaque reduction, yield reduction, and cytopathic effect inhibition), the ranking of the interferon sensitivities of different viruses was not changed. These results indicate that the relative sensitivity of a virus to interferon is determined by the host cells in which the tests are performed, but not by assay method used."}
{"id": "PMID:198375", "title": "Characterization of SA12 as a simian virus 40-related papovavirus of chacma baboons.", "content": "SA12 virus, originally isolated from an uninoculated South African vervet monkey kidney culture, was identified as a new member of the simian virus 40 (SV40)-polyoma subgroup of papovaviruses. The virus produced a cytopathic effect with nuclear enlargement in primary rhesus kidney cells. The virion had papovavirus morphology and a diameter of 44 to 45 nm. The DNA of the virus was a circular, double-stranded, superhelical molecule with a mean length 101% that of SV40 DNA and an estimated molecular weight of 3.3 X 10(6). The virus was found to be unrelated to other papovaviruses by neutralization, immune electron microscopy, and immunofluorescence tests with antiviral sera. SA12 virus-infected cells exhibited a capsid antigen, which has recently been found to be common to viruses of the SV40-polyoma subgroup. The virus readily transformed kideny cells from 10-day-old hamsters. Inoculation of transformed cells produced tumors in 3- to 4-week-old hamsters. The T antigens of SA12 and SV40 viruses were strongly and reciprocally cross-reactive. A high proportion of the sera of chacma baboons, Papio ursinus, and a comparatively lower proportion of the sera of vervet monkeys, Cercopithecus pygerythrus, had neutralizing antibodies to SA12 virus", "contents": "Characterization of SA12 as a simian virus 40-related papovavirus of chacma baboons. SA12 virus, originally isolated from an uninoculated South African vervet monkey kidney culture, was identified as a new member of the simian virus 40 (SV40)-polyoma subgroup of papovaviruses. The virus produced a cytopathic effect with nuclear enlargement in primary rhesus kidney cells. The virion had papovavirus morphology and a diameter of 44 to 45 nm. The DNA of the virus was a circular, double-stranded, superhelical molecule with a mean length 101% that of SV40 DNA and an estimated molecular weight of 3.3 X 10(6). The virus was found to be unrelated to other papovaviruses by neutralization, immune electron microscopy, and immunofluorescence tests with antiviral sera. SA12 virus-infected cells exhibited a capsid antigen, which has recently been found to be common to viruses of the SV40-polyoma subgroup. The virus readily transformed kideny cells from 10-day-old hamsters. Inoculation of transformed cells produced tumors in 3- to 4-week-old hamsters. The T antigens of SA12 and SV40 viruses were strongly and reciprocally cross-reactive. A high proportion of the sera of chacma baboons, Papio ursinus, and a comparatively lower proportion of the sera of vervet monkeys, Cercopithecus pygerythrus, had neutralizing antibodies to SA12 virus"}
{"id": "PMID:198376", "title": "Polymorphonuclear leukocyte bactericidal activity and oxidative metabolism during glutathione peroxidase deficiency.", "content": "Glutathione peroxidase (GPx) deficiency has been proposed as a cause of some instances of chronic granulomatous disease (CGD). GPx activity varies greatly among species, and specific deficiency of this selenium-dependent enzyme can be produced by dietary selenium deficiency in rats. Bactericidal activity of polymorphonuclear (PMN) leukocytes from normal rats, humans, and guinea pigs (GPx high, intermediate, and nearly absent, respectively), selenium-deficient rats (GPx absent), and a patient with CGD were compared. There was no correlation between natural levels of GPx and bactericidal activity; only CGD was associated with inability to kill a Proteus mirabilis strain in vitro (killing known to be dependent on oxidative mechanisms). Postphagocytic metabolism was examined in normal and GPx-deficient rats. Both demonstrated normal iodination and superoxide production during phagocytosis and gave similar histochemical reduction of nitroblue tetrazolium dye under either resting or endotoxin-stimulation conditions. Postphagocytic hexose monophosphate shunt activity was somewhat lower in PMN from GPx-deficient animals as compared with normal but was substantially (10-fold) higher than that observed in resting cells. Thus, postphagocytic oxidative responses and subsequent bactericidal activity of PMN leukocytes were not compromised by complete absence of GPx, even in the species with the highest natural level of this enzyme. These results are not compatible with the hypothesis that CGD can be caused by a deficiency of GPx.", "contents": "Polymorphonuclear leukocyte bactericidal activity and oxidative metabolism during glutathione peroxidase deficiency. Glutathione peroxidase (GPx) deficiency has been proposed as a cause of some instances of chronic granulomatous disease (CGD). GPx activity varies greatly among species, and specific deficiency of this selenium-dependent enzyme can be produced by dietary selenium deficiency in rats. Bactericidal activity of polymorphonuclear (PMN) leukocytes from normal rats, humans, and guinea pigs (GPx high, intermediate, and nearly absent, respectively), selenium-deficient rats (GPx absent), and a patient with CGD were compared. There was no correlation between natural levels of GPx and bactericidal activity; only CGD was associated with inability to kill a Proteus mirabilis strain in vitro (killing known to be dependent on oxidative mechanisms). Postphagocytic metabolism was examined in normal and GPx-deficient rats. Both demonstrated normal iodination and superoxide production during phagocytosis and gave similar histochemical reduction of nitroblue tetrazolium dye under either resting or endotoxin-stimulation conditions. Postphagocytic hexose monophosphate shunt activity was somewhat lower in PMN from GPx-deficient animals as compared with normal but was substantially (10-fold) higher than that observed in resting cells. Thus, postphagocytic oxidative responses and subsequent bactericidal activity of PMN leukocytes were not compromised by complete absence of GPx, even in the species with the highest natural level of this enzyme. These results are not compatible with the hypothesis that CGD can be caused by a deficiency of GPx."}
{"id": "PMID:198377", "title": "Beta-adrenergic blocking activity of Yersinia pestis murine toxin.", "content": "Yersinia pestis plague murine toxin has been found to inhibit the mobilization of free fatty acids in mice in a manner similar to that of beta-adrenergic blocking agents. The blockage is detectable 75 min after injection of the toxin (1 to 2 mean lethal doses). The degree of inhibition was directly correlated with the toxicity of a given toxin preparation. Agents such as cholera toxin or glucagon, with apparently distinct receptors from beta-adrenergic receptors, stimulated adenylate cyclase and lipolysis and effectively modified toxicity. Likewise, cyclic adenosine 3',5'-monophosphate bypassed the toxin block and antagonized toxicity. Energy-rich compounds such as fatty acids, organic acids, and glucose effectively modified the intoxication process. The biological activity of plague toxin showed profound temperature sensitivity. Mice placed at 5 degrees C were highly susceptible to the effects of the toxin, whereas mice placed at 37 degrees C were totally resistant to intoxication. Results showed that plague toxin cannot block epinephrine-induced mobilization of free fatty acids in mice placed at 37 degrees C. These studies suggested that plague toxin acts at the receptor level in a manner similar to that of beta-adrenergic blocking agents. A complete, analogous activity was shown between toxin and known beta-adrenergic antagonists in their effect on beta-adrenergic agonist action in stimulating lipolysis. It is hypothesized that, since toxin shows no in vitro activity, it is in some way modified in animals.", "contents": "Beta-adrenergic blocking activity of Yersinia pestis murine toxin. Yersinia pestis plague murine toxin has been found to inhibit the mobilization of free fatty acids in mice in a manner similar to that of beta-adrenergic blocking agents. The blockage is detectable 75 min after injection of the toxin (1 to 2 mean lethal doses). The degree of inhibition was directly correlated with the toxicity of a given toxin preparation. Agents such as cholera toxin or glucagon, with apparently distinct receptors from beta-adrenergic receptors, stimulated adenylate cyclase and lipolysis and effectively modified toxicity. Likewise, cyclic adenosine 3',5'-monophosphate bypassed the toxin block and antagonized toxicity. Energy-rich compounds such as fatty acids, organic acids, and glucose effectively modified the intoxication process. The biological activity of plague toxin showed profound temperature sensitivity. Mice placed at 5 degrees C were highly susceptible to the effects of the toxin, whereas mice placed at 37 degrees C were totally resistant to intoxication. Results showed that plague toxin cannot block epinephrine-induced mobilization of free fatty acids in mice placed at 37 degrees C. These studies suggested that plague toxin acts at the receptor level in a manner similar to that of beta-adrenergic blocking agents. A complete, analogous activity was shown between toxin and known beta-adrenergic antagonists in their effect on beta-adrenergic agonist action in stimulating lipolysis. It is hypothesized that, since toxin shows no in vitro activity, it is in some way modified in animals."}
{"id": "PMID:198378", "title": "Establishment of simian sarcoma virus, type 1 (SSV-1)-transformed non-producer marmoset cell lines.", "content": "Simian sarcoma virus, type 1 (SSV-1)-transformed non-producer cell lines were established by infection of normal marmoset fibroblast cells (HF) with limiting dilutions of SSV-1. Four focus-derived cell lines were identified as non-producers by assay of culture fluids for focus-forming activity and by the mixed culture cytopathogenicity test with XC cells. Further studies failed to detect production of type-C virus by 3H-uridine labelling, reverse transcriptase assay or electron microscopy. The non-producer cell lines, designated HF/SSV-NPI, IV, V, and VI, appeared morphologically transformed and cloned in soft agar with the same efficiency as HF/SSV-1 virus-producing transformed cells. Expression of either cytoplasmic or cell surface virus-related antigens was not detected by immunofluorescence or serum cytotoxicity tests. The presence of sarcoma genome in the transformed non-producer cell lines was demonstrated by rescue of focus-forming activity following superinfection with non-transforming helper virus or by cocultivation with helper-virus-producing cell lines. The SSV-1-transformed non-producer primate cells provide a useful tool for future studies.", "contents": "Establishment of simian sarcoma virus, type 1 (SSV-1)-transformed non-producer marmoset cell lines. Simian sarcoma virus, type 1 (SSV-1)-transformed non-producer cell lines were established by infection of normal marmoset fibroblast cells (HF) with limiting dilutions of SSV-1. Four focus-derived cell lines were identified as non-producers by assay of culture fluids for focus-forming activity and by the mixed culture cytopathogenicity test with XC cells. Further studies failed to detect production of type-C virus by 3H-uridine labelling, reverse transcriptase assay or electron microscopy. The non-producer cell lines, designated HF/SSV-NPI, IV, V, and VI, appeared morphologically transformed and cloned in soft agar with the same efficiency as HF/SSV-1 virus-producing transformed cells. Expression of either cytoplasmic or cell surface virus-related antigens was not detected by immunofluorescence or serum cytotoxicity tests. The presence of sarcoma genome in the transformed non-producer cell lines was demonstrated by rescue of focus-forming activity following superinfection with non-transforming helper virus or by cocultivation with helper-virus-producing cell lines. The SSV-1-transformed non-producer primate cells provide a useful tool for future studies."}
{"id": "PMID:198379", "title": "Susceptibility to and escape from complement-mediated lysis of guinea-pig hepatoma line-10.", "content": "Rabbit xenoantisera produced against diethyl-nitrosamine-induced strain-2 guinea-pig hepatoma line-10 cells (L-10) according to various immunization schedules were compared for their cytotoxicity on L-10 cells in the presence of guinea-pig complement. The highest activity was obtained with antisera (Cx-1) produced by repeated intravenous injections of living L-10 cells at high cell dosage, whereas intramuscular injections of living or glutaraldehyde-treated L-10 cells at similar frequency and cell dosage were less effective for the production of cytotoxic antibodies against L-10 cells. Intravenous injections of smaller cell doses were less effective. The cytotoxic antibody in Cx-1 antiserum was shown to be IgG by various methods including gel filtration on Sephadex G-200, ion exchange chromatography and immunoelectrophoresis of purified tumor-specific antibodies. It was concluded that L-10 cells can be lysed by guinea-pig complement and tumor-specific antibodies (IgG). Some antisera contained IgM antibodies which were not cytotoxic. A decrease in susceptibility of L-10 cells to complement-mediated lysis was observed when the cells were maintained in vivo for a long period (more than 20 passage generations). This was due to a lower density of tumor antigens on the cell surface. When tumor cells were treated with a second antibody directed against rabbit IgG or F(ab')2, cytotoxicity of Cx-1 antisera was completely abolished.", "contents": "Susceptibility to and escape from complement-mediated lysis of guinea-pig hepatoma line-10. Rabbit xenoantisera produced against diethyl-nitrosamine-induced strain-2 guinea-pig hepatoma line-10 cells (L-10) according to various immunization schedules were compared for their cytotoxicity on L-10 cells in the presence of guinea-pig complement. The highest activity was obtained with antisera (Cx-1) produced by repeated intravenous injections of living L-10 cells at high cell dosage, whereas intramuscular injections of living or glutaraldehyde-treated L-10 cells at similar frequency and cell dosage were less effective for the production of cytotoxic antibodies against L-10 cells. Intravenous injections of smaller cell doses were less effective. The cytotoxic antibody in Cx-1 antiserum was shown to be IgG by various methods including gel filtration on Sephadex G-200, ion exchange chromatography and immunoelectrophoresis of purified tumor-specific antibodies. It was concluded that L-10 cells can be lysed by guinea-pig complement and tumor-specific antibodies (IgG). Some antisera contained IgM antibodies which were not cytotoxic. A decrease in susceptibility of L-10 cells to complement-mediated lysis was observed when the cells were maintained in vivo for a long period (more than 20 passage generations). This was due to a lower density of tumor antigens on the cell surface. When tumor cells were treated with a second antibody directed against rabbit IgG or F(ab')2, cytotoxicity of Cx-1 antisera was completely abolished."}
{"id": "PMID:198380", "title": "Epstein-Barr herpesvirus infection: inhibition by immunologically induced mediators with interferon-like properties.", "content": "When sensitized leukocytes were re-exposed to EBV antigen or to tuberculin-purified protein derivatives, they produced lymphokines, including the migration inhibition factor, which inhibited the migration of guinea-pig peritoneal exudate cells, and other lymphokines with the characteristics of interferon, which inhibited EBV-induced transformation and EBV superinfection of target cells. Unsensitized leucocytes from sero-negative adults and from neonates did not produce lymphokines when challenged with the antigens. This indicates that cell-mediated immunity and its associated soluble mediators may be involved in the control of EBV infection and that the interferon release assay is a useful in vitro correlate for the study of cellular immunity to EBV.", "contents": "Epstein-Barr herpesvirus infection: inhibition by immunologically induced mediators with interferon-like properties. When sensitized leukocytes were re-exposed to EBV antigen or to tuberculin-purified protein derivatives, they produced lymphokines, including the migration inhibition factor, which inhibited the migration of guinea-pig peritoneal exudate cells, and other lymphokines with the characteristics of interferon, which inhibited EBV-induced transformation and EBV superinfection of target cells. Unsensitized leucocytes from sero-negative adults and from neonates did not produce lymphokines when challenged with the antigens. This indicates that cell-mediated immunity and its associated soluble mediators may be involved in the control of EBV infection and that the interferon release assay is a useful in vitro correlate for the study of cellular immunity to EBV."}
{"id": "PMID:198381", "title": "Comparative studies on immunity to EBV-associated antigens in NPC patients in North America, Tunisia, France and Hong Kong.", "content": "This study compared the relative antibody titers to EBV-related antigens in patients with nasopharyngeal carcinoma (NPC) and controls from a high-incidence (Hong Kong), an intermediate incidence (Tunisia), and two low-incidence (France, North America) areas to determine which of several EBV antibodies best differentiated NPC patients from controls. Antibodies measured include anti-virus capsid antigen (VCA), anti-early antigen (EA), anti-soluble antigen by complement-fixation (CF) and antibody-dependent lymphocyte cytotoxicity (ADLC). A matched pair analysis showed that significantly more NPC patients had higher VCA and EA but not CF or ADLC antibody titers than their matched cancer controls. The comparison of geometric mean titers between NPC cases and controls was more than seven-fold (816 vs 11.5) for EA antibody and more than three-fold (359.7 vs 95.4) for VCA anti-body (p less than 0.01). A two-fold difference was seen for CF antibody to soluble antigens (27.3 vs 12.9, p less than 0.01) and a three-fold difference (2657.7 vs 870.9, p less than 0.05) was observed for ADLC. Our finding of significant differences between NPC patients from four countries and their matched controls suggest that if EBV is the etiological agent of NPC in Chinese, it is quite likely to cause the majority of NPC cases in other ethnic groups living in other countries as well.", "contents": "Comparative studies on immunity to EBV-associated antigens in NPC patients in North America, Tunisia, France and Hong Kong. This study compared the relative antibody titers to EBV-related antigens in patients with nasopharyngeal carcinoma (NPC) and controls from a high-incidence (Hong Kong), an intermediate incidence (Tunisia), and two low-incidence (France, North America) areas to determine which of several EBV antibodies best differentiated NPC patients from controls. Antibodies measured include anti-virus capsid antigen (VCA), anti-early antigen (EA), anti-soluble antigen by complement-fixation (CF) and antibody-dependent lymphocyte cytotoxicity (ADLC). A matched pair analysis showed that significantly more NPC patients had higher VCA and EA but not CF or ADLC antibody titers than their matched cancer controls. The comparison of geometric mean titers between NPC cases and controls was more than seven-fold (816 vs 11.5) for EA antibody and more than three-fold (359.7 vs 95.4) for VCA anti-body (p less than 0.01). A two-fold difference was seen for CF antibody to soluble antigens (27.3 vs 12.9, p less than 0.01) and a three-fold difference (2657.7 vs 870.9, p less than 0.05) was observed for ADLC. Our finding of significant differences between NPC patients from four countries and their matched controls suggest that if EBV is the etiological agent of NPC in Chinese, it is quite likely to cause the majority of NPC cases in other ethnic groups living in other countries as well."}
{"id": "PMID:198382", "title": "Membrane receptor stripping confirms the association between EBV receptors and complement receptors on the surface of human B lymphoma lines.", "content": "Complement (C3) receptors, EBV receptors, Fc receptors, membrane IgM and beta2microglobulin (beta 2m) were individually stripped from the surface of human B lymphoma lines. The cells were subsequently tested for their ability to absorb infectious EB virus. Stripping of Fc receptors, IgM and beta2m did not reduce EBV absorption. Stripping of either EBV receptors or C3 receptors eliminated or drastically reduced EBV-absorptive capacity. The results confirm the distinctive association between EBV receptors and C3 receptors on human lymphoma cells.", "contents": "Membrane receptor stripping confirms the association between EBV receptors and complement receptors on the surface of human B lymphoma lines. Complement (C3) receptors, EBV receptors, Fc receptors, membrane IgM and beta2microglobulin (beta 2m) were individually stripped from the surface of human B lymphoma lines. The cells were subsequently tested for their ability to absorb infectious EB virus. Stripping of Fc receptors, IgM and beta2m did not reduce EBV absorption. Stripping of either EBV receptors or C3 receptors eliminated or drastically reduced EBV-absorptive capacity. The results confirm the distinctive association between EBV receptors and C3 receptors on human lymphoma cells."}
{"id": "PMID:198383", "title": "Factors interfering with cellular immunological responses to the murine mammary tumor virus in tumor-bearing mice.", "content": "T-cell-enriched spleen cell fractions from BALB/c mice bearing virally induced mammary tumors become unresponsive with progressive tumor growth in the lymphocyte blastogenesis test, using purified mammary tumor virus (MTV) as an antigen. reactivity can be restored by mild trypsinization or extensive washing of the cells. When reactive cells from mice immunized with MTV were incubated with the wash fluid of the initially unresponsive cells. MTV-specific blastogenesis was inhibited. Washings of normal cells had no such effect. Leukocytes from tumor-bearing mice also become unresponsive to MTV in the leukocyte adherence inhibition (LAI) assay. Trypsinization or extensive washing does not restore reactivity. However, such treatment of reactive cells from immunized animals abolishes a positive reaction in the LAI assay, using MTV as an antigen. The washings of spleen cells from tumor-bearing mice inhibit the reactivity of leukocytes from immunized animals. Sera from these mice could block the reaction in both cellular immunological tests. The inhibiting factors appeared early after the onset of tumor growth. By means of the Sepharose bead immunofluorescence assay it was established that wash fluid and sera with blocking activity contain MTV antigens as well as anti-MTV antibodies.", "contents": "Factors interfering with cellular immunological responses to the murine mammary tumor virus in tumor-bearing mice. T-cell-enriched spleen cell fractions from BALB/c mice bearing virally induced mammary tumors become unresponsive with progressive tumor growth in the lymphocyte blastogenesis test, using purified mammary tumor virus (MTV) as an antigen. reactivity can be restored by mild trypsinization or extensive washing of the cells. When reactive cells from mice immunized with MTV were incubated with the wash fluid of the initially unresponsive cells. MTV-specific blastogenesis was inhibited. Washings of normal cells had no such effect. Leukocytes from tumor-bearing mice also become unresponsive to MTV in the leukocyte adherence inhibition (LAI) assay. Trypsinization or extensive washing does not restore reactivity. However, such treatment of reactive cells from immunized animals abolishes a positive reaction in the LAI assay, using MTV as an antigen. The washings of spleen cells from tumor-bearing mice inhibit the reactivity of leukocytes from immunized animals. Sera from these mice could block the reaction in both cellular immunological tests. The inhibiting factors appeared early after the onset of tumor growth. By means of the Sepharose bead immunofluorescence assay it was established that wash fluid and sera with blocking activity contain MTV antigens as well as anti-MTV antibodies."}
{"id": "PMID:198385", "title": "Dose-response curves of gamma-irradiated purine and pyrimidine powders.", "content": "E.s.r. spectra have been obtained of gamma-irradiated dry purine and pyrimidine powders. Relative radical yields have been calculated and dose-response curves obtained. Relative recombination rates and recombination rates and formation rates of the radicals have been derived from the dose-response curves. The effect of crystalline structure on the dose-response curves is discussed.", "contents": "Dose-response curves of gamma-irradiated purine and pyrimidine powders. E.s.r. spectra have been obtained of gamma-irradiated dry purine and pyrimidine powders. Relative radical yields have been calculated and dose-response curves obtained. Relative recombination rates and recombination rates and formation rates of the radicals have been derived from the dose-response curves. The effect of crystalline structure on the dose-response curves is discussed."}
{"id": "PMID:198386", "title": "E.s.r. radiation studies of erythrocyte membrane haemoglobin interaction.", "content": "The dependence of the yield of free radicals in gamma-irradiated, freeze-dried erythrocyte membranes on their haemoglobin content was studied. A non-monotonous relationship was found--different from that observed in mixtures of freeze-dried membranes and haemoglobin, which suggests the existence of radiation-energy transfer between the membranes and bound haemoglobin.", "contents": "E.s.r. radiation studies of erythrocyte membrane haemoglobin interaction. The dependence of the yield of free radicals in gamma-irradiated, freeze-dried erythrocyte membranes on their haemoglobin content was studied. A non-monotonous relationship was found--different from that observed in mixtures of freeze-dried membranes and haemoglobin, which suggests the existence of radiation-energy transfer between the membranes and bound haemoglobin."}
{"id": "PMID:198384", "title": "Cytochrome-linked respiration in host grown M. leprae isolated from an Armadillo (Dasypus novemcinctus, L.).", "content": "The bacilli were isolated from an armadillo (Dasypus novemcinctus, L.) and cytochrome systems as well as oxidation of succinate and NADH by M. leprae were studied. Cell-free extracts of M. leprae contained cytochromes of the a + a3, b, c and o type. Whole cell suspensions catalyzed the oxidation of succinate. The process was unaffected by rotenone but was markedly inhibited by thenoyltrifluoroacetone, antimycin A and cyanide. Cell-free preparations of M. leprae also oxidized NADH with oxygen as the terminal electron acceptor. Although NADH oxidation was completely inhibited by rotenone, the process was inhibited to only 50% by 5 millimols cyanide. The results indicated that complete respiratory system is present in M. leprae isolated from leprous tissues of an armadillo. The effect of inhibitors on succinate and NADH oxidations showed that the respiration in host-grown M. leprae is mediated through the cytochrome system with oxygen as the final electron acceptor.", "contents": "Cytochrome-linked respiration in host grown M. leprae isolated from an Armadillo (Dasypus novemcinctus, L.). The bacilli were isolated from an armadillo (Dasypus novemcinctus, L.) and cytochrome systems as well as oxidation of succinate and NADH by M. leprae were studied. Cell-free extracts of M. leprae contained cytochromes of the a + a3, b, c and o type. Whole cell suspensions catalyzed the oxidation of succinate. The process was unaffected by rotenone but was markedly inhibited by thenoyltrifluoroacetone, antimycin A and cyanide. Cell-free preparations of M. leprae also oxidized NADH with oxygen as the terminal electron acceptor. Although NADH oxidation was completely inhibited by rotenone, the process was inhibited to only 50% by 5 millimols cyanide. The results indicated that complete respiratory system is present in M. leprae isolated from leprous tissues of an armadillo. The effect of inhibitors on succinate and NADH oxidations showed that the respiration in host-grown M. leprae is mediated through the cytochrome system with oxygen as the final electron acceptor."}
{"id": "PMID:198392", "title": "Cytochemical contributions to differentiating GERL from the Golgi apparatus.", "content": "Recent studies from our laboratory are described which deal with endocrine cells (insulinoma, beta-cells of the pancreas, thyroid epithelial cells), pancreatic exocrine cells, and hepatocytes. These emphasize the importance of the hydrolase-rich specialized region of endoplasmic reticulum, known as GERL, in secretory cells. Also reviewed in this paper are the varied molecular transformations which apparently occur in GERL in different cell types, as reported from other laboratories as well as our own. Evidence of the continuity of GERL with rough endoplasmic reticulum is presented. Two hydrolytic enzyme activities in GERL, in addition to acid phosphatase activity, are recorded. Finally, the use of cytochemical staining procedures in the study of microperoxisomes is briefly described.", "contents": "Cytochemical contributions to differentiating GERL from the Golgi apparatus. Recent studies from our laboratory are described which deal with endocrine cells (insulinoma, beta-cells of the pancreas, thyroid epithelial cells), pancreatic exocrine cells, and hepatocytes. These emphasize the importance of the hydrolase-rich specialized region of endoplasmic reticulum, known as GERL, in secretory cells. Also reviewed in this paper are the varied molecular transformations which apparently occur in GERL in different cell types, as reported from other laboratories as well as our own. Evidence of the continuity of GERL with rough endoplasmic reticulum is presented. Two hydrolytic enzyme activities in GERL, in addition to acid phosphatase activity, are recorded. Finally, the use of cytochemical staining procedures in the study of microperoxisomes is briefly described."}
{"id": "PMID:198394", "title": "Mechanics of the rib cage and diaphragm during sleep.", "content": "The pattern of motion of the rib cage and abdomen/diaphragm was studied in three normal subjects during sleep. Sleep state was monitored by electroencephalograph and electrocculograph. Intercostal electromyographs (EMG's) were recorded from the second interspace parasternally. Abdominothoracic motion was monitored with magnetometers and these signals calibrated by isovolume lines either immediately before going to sleep, or if there was movement, on awakening. Respiration was recorded using a jerkin plethysmograph. In the awake subject in the supine position, the rib cage contributed 44% to the tidal volume and had essentially the same contribution in quiet sleep. However, in active or rapid eye movement sleep the rib cage contribution fell to 19% of the tidal volume. This was accompanied by a marked reduction in the intercostal EMG. With the subject in the upright position the rib cage appears to be passively driven by the diaphragm. However, the present data suggest that active contraction of the intercostal muscles is required for normal rib cage expansion in the supine position.", "contents": "Mechanics of the rib cage and diaphragm during sleep. The pattern of motion of the rib cage and abdomen/diaphragm was studied in three normal subjects during sleep. Sleep state was monitored by electroencephalograph and electrocculograph. Intercostal electromyographs (EMG's) were recorded from the second interspace parasternally. Abdominothoracic motion was monitored with magnetometers and these signals calibrated by isovolume lines either immediately before going to sleep, or if there was movement, on awakening. Respiration was recorded using a jerkin plethysmograph. In the awake subject in the supine position, the rib cage contributed 44% to the tidal volume and had essentially the same contribution in quiet sleep. However, in active or rapid eye movement sleep the rib cage contribution fell to 19% of the tidal volume. This was accompanied by a marked reduction in the intercostal EMG. With the subject in the upright position the rib cage appears to be passively driven by the diaphragm. However, the present data suggest that active contraction of the intercostal muscles is required for normal rib cage expansion in the supine position."}
{"id": "PMID:198395", "title": "beta-Receptor influence on lung vasoconstrictor responses to hypoxia and humoral agents.", "content": "The role of the adrenergic receptor in mediating pulmonary vascular responses to gaseous and humoral agents was investigated by use of epinephrine injections in the perfused feline pulmonary circulation. Alteration of the balance between alpha- and beta-adrenergic activity was quantified by measurement of decreasing vasoconstrictor activity to epinephrine and rising lobar tissue 3',5'-adenosine cyclic monophosphate (cAMP) levels. The increased beta-adrenergic activity thus generated was associated with marked reductions in the pulmonary vasoconstrictor responses to hypoxia, hypercapnic acidosis, and histamine, but not to serotonin. Repeated pulmonary vasodilations or increases in blood, but not pulmonary tissue, levels of cAMP induced by theophylline doses, which would not necessarily affect the beta-adrenergic activity, did not alter the pulmonary vasoconstrictor responses to hypoxia, hypercapnia, or histamine. These data support the significant role which the adrenergic system plays in mediating pulmonary vasoconstrictor responses to certain specific gaseous and humoral agents, and the specificity with which this mediation occurs serves to link hypoxia and histamine together so that the latter could serve as a mediator of the former.", "contents": "beta-Receptor influence on lung vasoconstrictor responses to hypoxia and humoral agents. The role of the adrenergic receptor in mediating pulmonary vascular responses to gaseous and humoral agents was investigated by use of epinephrine injections in the perfused feline pulmonary circulation. Alteration of the balance between alpha- and beta-adrenergic activity was quantified by measurement of decreasing vasoconstrictor activity to epinephrine and rising lobar tissue 3',5'-adenosine cyclic monophosphate (cAMP) levels. The increased beta-adrenergic activity thus generated was associated with marked reductions in the pulmonary vasoconstrictor responses to hypoxia, hypercapnic acidosis, and histamine, but not to serotonin. Repeated pulmonary vasodilations or increases in blood, but not pulmonary tissue, levels of cAMP induced by theophylline doses, which would not necessarily affect the beta-adrenergic activity, did not alter the pulmonary vasoconstrictor responses to hypoxia, hypercapnia, or histamine. These data support the significant role which the adrenergic system plays in mediating pulmonary vasoconstrictor responses to certain specific gaseous and humoral agents, and the specificity with which this mediation occurs serves to link hypoxia and histamine together so that the latter could serve as a mediator of the former."}
{"id": "PMID:198396", "title": "Time course of muscular atrophy during immobilization of hindlimbs in rats.", "content": "The hindlimbs of rats were immobilized, in plaster casts, for varying durations, and the time course for atrophy of muscle and of selected proteins in these muscles was determined. In those muscles whose lengths were at less than resting length during the fixation procedures, exponential decay to a new apparent steady state after atrophy was shown by wet and dry muscle weights and by the amounts of biuret protein, cytochrome c, and citrate synthase. The time taken to decrease to one-half of the final decrease at the new apparent steady state level was about 4-6 days for the above parameters which decayed exponentially. In contrast, the myoglobin concentration increased during atrophy and the amount of myoglobin remain unchanged during atrophy. When fixation procedures on limbs were such that muscles were stretched to lengths greater than resting length, then the onset of atrophy was delayed; indeed, in some cases muscles hypertrophied when fixed in the stretched position.", "contents": "Time course of muscular atrophy during immobilization of hindlimbs in rats. The hindlimbs of rats were immobilized, in plaster casts, for varying durations, and the time course for atrophy of muscle and of selected proteins in these muscles was determined. In those muscles whose lengths were at less than resting length during the fixation procedures, exponential decay to a new apparent steady state after atrophy was shown by wet and dry muscle weights and by the amounts of biuret protein, cytochrome c, and citrate synthase. The time taken to decrease to one-half of the final decrease at the new apparent steady state level was about 4-6 days for the above parameters which decayed exponentially. In contrast, the myoglobin concentration increased during atrophy and the amount of myoglobin remain unchanged during atrophy. When fixation procedures on limbs were such that muscles were stretched to lengths greater than resting length, then the onset of atrophy was delayed; indeed, in some cases muscles hypertrophied when fixed in the stretched position."}
{"id": "PMID:198398", "title": "Purification and properties of poly(adenosine diphosphate ribose) synthetase.", "content": "Poly(ADP-ribose) synthetase has been purified approximately 5000-fold from rat liver nuclei. The activity of the purified enzyme is absolutely dependent upon the presence of native or synthetic DNA, and the further addition of histone(s) stimulates the activity 3- to 5-fold. When the ADP-ribosylated material synthesized in the absence or presence of various histones is analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the major product in all cases migrates between histones H1 and H3-H2B with the same RF value of 0.58 relative to the marker dye. No ADP-ribose was found to co-electrophorese with any of thehistones. The addition of histones does not affect the chain number of the poly(ADP-ribose) synthesized but does result in an increase in the average chain length of the polymer. In the presence of histones, the Km for NAD+ decreases from 80 micron to 25 micron and the Vmax doubles. These results indicate that, in the purified poly(ADP-ribose) synthetase system, histones are not ADP-robosylated but act as allosteric activators.", "contents": "Purification and properties of poly(adenosine diphosphate ribose) synthetase. Poly(ADP-ribose) synthetase has been purified approximately 5000-fold from rat liver nuclei. The activity of the purified enzyme is absolutely dependent upon the presence of native or synthetic DNA, and the further addition of histone(s) stimulates the activity 3- to 5-fold. When the ADP-ribosylated material synthesized in the absence or presence of various histones is analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the major product in all cases migrates between histones H1 and H3-H2B with the same RF value of 0.58 relative to the marker dye. No ADP-ribose was found to co-electrophorese with any of thehistones. The addition of histones does not affect the chain number of the poly(ADP-ribose) synthesized but does result in an increase in the average chain length of the polymer. In the presence of histones, the Km for NAD+ decreases from 80 micron to 25 micron and the Vmax doubles. These results indicate that, in the purified poly(ADP-ribose) synthetase system, histones are not ADP-robosylated but act as allosteric activators."}
{"id": "PMID:198399", "title": "Crystalline alkaline form fructose-1,6-diphosphatase. A simple purification procedure and preliminary x-ray diffraction analysis.", "content": "A simple and rapid procedure has been found for the preparation of higly pure alkaline form fructose-1,6-diphosphatase from turkey liver. The protein is tetrameric and is composed of subunits comprised of a 29,000 molecular weight core fragment and an associated 7,000-dalton S-peptide. Large single crystals of the protein, suitable for x-ray diffraction analysis, are produced in the course of the preparation. These are of space group R3 and have rhombohedral cell dimensions of a = 153 A and delta = 163 degrees (equivalent hexagonal dimensions a = 303 A, c = 75 A). There is one entire tetramer of 144,000 daltons in the asymmetric unit. The enzymatic properties of this enzyme appear to be very similar to those reported for the protein from other organisms, but its unique propensity to crystallize opens the way for a full three-dimensional structural analysis.", "contents": "Crystalline alkaline form fructose-1,6-diphosphatase. A simple purification procedure and preliminary x-ray diffraction analysis. A simple and rapid procedure has been found for the preparation of higly pure alkaline form fructose-1,6-diphosphatase from turkey liver. The protein is tetrameric and is composed of subunits comprised of a 29,000 molecular weight core fragment and an associated 7,000-dalton S-peptide. Large single crystals of the protein, suitable for x-ray diffraction analysis, are produced in the course of the preparation. These are of space group R3 and have rhombohedral cell dimensions of a = 153 A and delta = 163 degrees (equivalent hexagonal dimensions a = 303 A, c = 75 A). There is one entire tetramer of 144,000 daltons in the asymmetric unit. The enzymatic properties of this enzyme appear to be very similar to those reported for the protein from other organisms, but its unique propensity to crystallize opens the way for a full three-dimensional structural analysis."}
{"id": "PMID:198403", "title": "Cyclic AMP and the plasma membrane potential in Neurospora crassa.", "content": "Diverse treatments, which have been shown by Slayman, C. L. (1977) in Water Relations in Membrane Transport in Plants and Animals (Jungreis, A., Hodges, T. K., Kleinzeller, A., and Schultz, S. G., eds) pp. 69-86, Academic Press, New York, to depolarize the plasma membrane of Neurospora, increase levels of adenosine 3':5'-monophosphate (cyclic AMP) in the organism. The treatments include those producing large transport fluxes of metabolizable or nonmetabolizable compounds, rapid temperature drops, and addition of agents which uncouple oxidative phosphorylation. Severe mechanical stress, which may also act to depolarize the plasma membrane, leads to increases in cyclic AMP. The maximal depolarization appears to precede the maximal cyclic AMP levels. It is proposed that the membrane depolarization produces the increased cyclic AMP levels by stimulating the plasma membrane-bound adenylate cyclase and that cyclic AMP may be important to the maintenance of membrane integrity.", "contents": "Cyclic AMP and the plasma membrane potential in Neurospora crassa. Diverse treatments, which have been shown by Slayman, C. L. (1977) in Water Relations in Membrane Transport in Plants and Animals (Jungreis, A., Hodges, T. K., Kleinzeller, A., and Schultz, S. G., eds) pp. 69-86, Academic Press, New York, to depolarize the plasma membrane of Neurospora, increase levels of adenosine 3':5'-monophosphate (cyclic AMP) in the organism. The treatments include those producing large transport fluxes of metabolizable or nonmetabolizable compounds, rapid temperature drops, and addition of agents which uncouple oxidative phosphorylation. Severe mechanical stress, which may also act to depolarize the plasma membrane, leads to increases in cyclic AMP. The maximal depolarization appears to precede the maximal cyclic AMP levels. It is proposed that the membrane depolarization produces the increased cyclic AMP levels by stimulating the plasma membrane-bound adenylate cyclase and that cyclic AMP may be important to the maintenance of membrane integrity."}
{"id": "PMID:198404", "title": "Mast cell binding of neurotensin. II. Molecular conformation of neurotensin involved in the stereospecific binding to mast cell receptor sites.", "content": "Systematic substitution of the natural L-amino acids in neurotensin by their D isomers reveals that the COOH-terminal portion of this tridecapeptide is required for binding to mast cell receptors: D-amino acid replacements from Pro10 through Leu13 substantially decrease that binding. Either blockage of the COOH-terminal carboxyl group as with N-methylamidation, or formation of a cyclic structure by the inclusion of a disulfide bond, a Cys2,13 substitution, markedly reduces the specific binding to mast cell receptor sites. Modifications in the NH2-terminal portion of neurotensin do not affect the binding to mast cells. However, D-Arg8 and D-Arg9 substitutions increase binding by factors of 5- to 6-fold. The hydroxyl group at position 3 or 11 is not essential for binding since Phe3 or Phe11 is equivalent to Tyr3 or Tyr11. The COOH-terminal penta- and hexapeptides are able to displace approximately 70% 125I-neurotensin relative to the intact peptide. Of 18 other biologically active peptides tested, only xenopsin, a naturally occurring COOH-terminal analog of neurotensin, and bradykinin effectively compete in the binding assay to an extent of 60 and 100%, respectively. Histamine, diphenhydramine, and noradrenaline are ineffective in this regard.", "contents": "Mast cell binding of neurotensin. II. Molecular conformation of neurotensin involved in the stereospecific binding to mast cell receptor sites. Systematic substitution of the natural L-amino acids in neurotensin by their D isomers reveals that the COOH-terminal portion of this tridecapeptide is required for binding to mast cell receptors: D-amino acid replacements from Pro10 through Leu13 substantially decrease that binding. Either blockage of the COOH-terminal carboxyl group as with N-methylamidation, or formation of a cyclic structure by the inclusion of a disulfide bond, a Cys2,13 substitution, markedly reduces the specific binding to mast cell receptor sites. Modifications in the NH2-terminal portion of neurotensin do not affect the binding to mast cells. However, D-Arg8 and D-Arg9 substitutions increase binding by factors of 5- to 6-fold. The hydroxyl group at position 3 or 11 is not essential for binding since Phe3 or Phe11 is equivalent to Tyr3 or Tyr11. The COOH-terminal penta- and hexapeptides are able to displace approximately 70% 125I-neurotensin relative to the intact peptide. Of 18 other biologically active peptides tested, only xenopsin, a naturally occurring COOH-terminal analog of neurotensin, and bradykinin effectively compete in the binding assay to an extent of 60 and 100%, respectively. Histamine, diphenhydramine, and noradrenaline are ineffective in this regard."}
{"id": "PMID:198409", "title": "Orthopaedic treatment of hemangiomatous hypertrophy of the lower extremity.", "content": "The triad of varicose veins, hypertrophy of soft tissue and bone, and cutaneous hemangiomas (The Klippel-Trenaunay syndrome) often results in major malformations. A review of eleven children treated for this condition showed that the overgrowth of the limb was a major problem in management. In three patients the altered hemodynamics resulted in cardiac complications. Venous stripping, excision of the arteriovenous fistulae, and radiation therapy should be avoided.", "contents": "Orthopaedic treatment of hemangiomatous hypertrophy of the lower extremity. The triad of varicose veins, hypertrophy of soft tissue and bone, and cutaneous hemangiomas (The Klippel-Trenaunay syndrome) often results in major malformations. A review of eleven children treated for this condition showed that the overgrowth of the limb was a major problem in management. In three patients the altered hemodynamics resulted in cardiac complications. Venous stripping, excision of the arteriovenous fistulae, and radiation therapy should be avoided."}
{"id": "PMID:198410", "title": "Abductor digiti quinti opponensplasty.", "content": "Fifteen neurovascular pedicle transfers of the abductor digiti quinti to the base of the proximal phalanx of the thumb were performed: seven for laceration of the median nerve, seven for neurological disease, and one for congenital absence of the thenar muscles. Fourteen of the transfers were viable, and twelve gave excellent results. The three failures all had had inadequate release of contractures of the thumb. This transfer offers the following advantages over other opponensplasties: (1) an intrinsic muscle with correct amplitude and direction of pull replaces intrinsic muscles; (2) the tension of the muscle transfer is automatically correct; and (3) the appearance of the hand after this procedure is superior to that after other types of opponensplasty.", "contents": "Abductor digiti quinti opponensplasty. Fifteen neurovascular pedicle transfers of the abductor digiti quinti to the base of the proximal phalanx of the thumb were performed: seven for laceration of the median nerve, seven for neurological disease, and one for congenital absence of the thenar muscles. Fourteen of the transfers were viable, and twelve gave excellent results. The three failures all had had inadequate release of contractures of the thumb. This transfer offers the following advantages over other opponensplasties: (1) an intrinsic muscle with correct amplitude and direction of pull replaces intrinsic muscles; (2) the tension of the muscle transfer is automatically correct; and (3) the appearance of the hand after this procedure is superior to that after other types of opponensplasty."}
{"id": "PMID:198411", "title": "Cyclic AMP-induced morphological transformation of cells infected by temperature-sensitive mouse sarcoma virus. Expression of transformation-associated markers.", "content": "Normal rat kidney (NRK) cells infected with a temperature-sensitive (ts) mutant of mouse sarcoma virus (NRK [MSV-1b]) express the transformed phenotype when grown under permissive conditions, but acquire the normal phenotype when grown under restrictive conditions. Addition of 3', 5' cyclic adenosine monophosphate (cAMP) to NRK (MSV-1b) cells grown at the restrictive temperature results in morphological transformation. To determine whether other markers associated with the transformed phenotype were coordinately expressed after cAMP exposure, concanavalin A (Con A) agglutinability, hexose transport rate, and incorporation of radioactively labeled fucose into fucolipid III and fucolipid IV (FL III and FL IV ) of the cells were examined. NRK cells transformed by wild-type MSV or NRK(MSV- 1b) grown under permissive conditions were agglutinated by low concentrations of Con A and exhibited relatively high maximal agglutination levels which were specifically inhibited by alpha-methyl-D-mannoside. In contrast, NRK (MSV-1b) cells grown under restrictive conditions were weakly agglutinated by Con A and exhibited reduced maximal agglutination levels, similar to uninfected NRK cells. Treatment of NRK (MSV-1b) cells at the restrictive temperature with cAMP resulted in morphological transformation and a change in the pattern of incorporation of labeled fucose inot FL III and FL IV to one comparable to that of NRK (MSV-1b) cells at the permissive temperature or to NRK cells transformed by wild-type MSV. In contrast, cAMP treatment resulted in no increase in Con A agglutinability or 2 deoxy-D- [(3)H]glucose transport relative to mock treated cultures. The results demonstrate that cAMP-induced morphological transformation and altered fucolipid composition of NRK (MSV-1b) cells are not correlated with alterations in hexose transport rate or Con A agglutinability.", "contents": "Cyclic AMP-induced morphological transformation of cells infected by temperature-sensitive mouse sarcoma virus. Expression of transformation-associated markers. Normal rat kidney (NRK) cells infected with a temperature-sensitive (ts) mutant of mouse sarcoma virus (NRK [MSV-1b]) express the transformed phenotype when grown under permissive conditions, but acquire the normal phenotype when grown under restrictive conditions. Addition of 3', 5' cyclic adenosine monophosphate (cAMP) to NRK (MSV-1b) cells grown at the restrictive temperature results in morphological transformation. To determine whether other markers associated with the transformed phenotype were coordinately expressed after cAMP exposure, concanavalin A (Con A) agglutinability, hexose transport rate, and incorporation of radioactively labeled fucose into fucolipid III and fucolipid IV (FL III and FL IV ) of the cells were examined. NRK cells transformed by wild-type MSV or NRK(MSV- 1b) grown under permissive conditions were agglutinated by low concentrations of Con A and exhibited relatively high maximal agglutination levels which were specifically inhibited by alpha-methyl-D-mannoside. In contrast, NRK (MSV-1b) cells grown under restrictive conditions were weakly agglutinated by Con A and exhibited reduced maximal agglutination levels, similar to uninfected NRK cells. Treatment of NRK (MSV-1b) cells at the restrictive temperature with cAMP resulted in morphological transformation and a change in the pattern of incorporation of labeled fucose inot FL III and FL IV to one comparable to that of NRK (MSV-1b) cells at the permissive temperature or to NRK cells transformed by wild-type MSV. In contrast, cAMP treatment resulted in no increase in Con A agglutinability or 2 deoxy-D- [(3)H]glucose transport relative to mock treated cultures. The results demonstrate that cAMP-induced morphological transformation and altered fucolipid composition of NRK (MSV-1b) cells are not correlated with alterations in hexose transport rate or Con A agglutinability."}
{"id": "PMID:198412", "title": "Iontophoretic release of cyclic AMP and dispersion of melanosomes within a single melanophore.", "content": "Selective dispersion of melanosomes was often observed after iontophoretic injection of cyclic adenosine monophosphate (AMP) from a glass microelectrode positioned in a target melanophore in frog skin (as viewed from above through a microscope), with other melanophores in the field serving as controls. Because the skin has orderly arrays of several types of closely spaced cells, it is probable that at times the microelectrode also impales cells other than melanophores. When cyclic AMP injection inside a cell resulted in dispersion of melanosomes from a perinuclear position into dendritic processes, the onset of dispersion was relatively rapid, in many cases less than 4 min (mean time of onset, 5.3 +/- 2.9 [SD] min). A much slower dispersion (mean time of onset, 19.0 +/- 5.0 min) of melanosomes was observed when the microelectrode was positioned adjacent to a melanophore, and much larger quantities of cyclic AMP were released. In addition, no changes were observed for injections of 5'-AMP or cyclic guanosine monophosphate (GMP) through electrodes positioned inside or adjacent to melanophores. Potential measurements showed that after impaling a clell, a constant transmembrane potential could often be recorded over many minutes, indicating that the membrane tends to seal around the microelectrode. The results indicate that cyclic AMP acts more rapidly on the inside of a cell than when applied outside a cell and allowed to diffuse through the plasma membrane. This study introduces a model system whereby the properties of the plasma membrane and melanocyte-stimulating hormone (MSH) receptors can be studies within a single target cell.", "contents": "Iontophoretic release of cyclic AMP and dispersion of melanosomes within a single melanophore. Selective dispersion of melanosomes was often observed after iontophoretic injection of cyclic adenosine monophosphate (AMP) from a glass microelectrode positioned in a target melanophore in frog skin (as viewed from above through a microscope), with other melanophores in the field serving as controls. Because the skin has orderly arrays of several types of closely spaced cells, it is probable that at times the microelectrode also impales cells other than melanophores. When cyclic AMP injection inside a cell resulted in dispersion of melanosomes from a perinuclear position into dendritic processes, the onset of dispersion was relatively rapid, in many cases less than 4 min (mean time of onset, 5.3 +/- 2.9 [SD] min). A much slower dispersion (mean time of onset, 19.0 +/- 5.0 min) of melanosomes was observed when the microelectrode was positioned adjacent to a melanophore, and much larger quantities of cyclic AMP were released. In addition, no changes were observed for injections of 5'-AMP or cyclic guanosine monophosphate (GMP) through electrodes positioned inside or adjacent to melanophores. Potential measurements showed that after impaling a clell, a constant transmembrane potential could often be recorded over many minutes, indicating that the membrane tends to seal around the microelectrode. The results indicate that cyclic AMP acts more rapidly on the inside of a cell than when applied outside a cell and allowed to diffuse through the plasma membrane. This study introduces a model system whereby the properties of the plasma membrane and melanocyte-stimulating hormone (MSH) receptors can be studies within a single target cell."}
{"id": "PMID:198413", "title": "Characterization of the myosin-phosphorylating system in normal murine astrocytes and derivative sv40 wild-type and A-mutant transformant.", "content": "Myosin and myosin light-chain kinase have been isolated and characterized from small quantities of normal and SV40-transformed, murine astrocytic neuroglial cells in culture and from intact normal mouse brain. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of the astrocyte myosins revealed a heavy chain of 200,000 daltons and two light chains of 20,000 and 15,000 daltons. These myosins are similar to other cytyplasmic myosins. The astrocyte 20,000-dalton light chain can be phosphorylated by an endogenous myosin light-chain kinase which has properties similar to those of the myosin light-chain kinase found in human platelets. No differences were detected in either the astrocyte myosins or myosin light-chain kinases between (a) the normal and transformed cells, (b) the transformed cells grown at the permissive and nonpermissive temperatures, or (c) the SV40 wild-type and A-mutant transformants.", "contents": "Characterization of the myosin-phosphorylating system in normal murine astrocytes and derivative sv40 wild-type and A-mutant transformant. Myosin and myosin light-chain kinase have been isolated and characterized from small quantities of normal and SV40-transformed, murine astrocytic neuroglial cells in culture and from intact normal mouse brain. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of the astrocyte myosins revealed a heavy chain of 200,000 daltons and two light chains of 20,000 and 15,000 daltons. These myosins are similar to other cytyplasmic myosins. The astrocyte 20,000-dalton light chain can be phosphorylated by an endogenous myosin light-chain kinase which has properties similar to those of the myosin light-chain kinase found in human platelets. No differences were detected in either the astrocyte myosins or myosin light-chain kinases between (a) the normal and transformed cells, (b) the transformed cells grown at the permissive and nonpermissive temperatures, or (c) the SV40 wild-type and A-mutant transformants."}
{"id": "PMID:198414", "title": "Locomotory behavior, contact inhibition and pattern formation of 3T3 and polyoma virus-transformed 3T3 cells in culture.", "content": "The social behavior of 3T3 cells and their polynoma virus-transformed derivative (Py3T3 cells) was examined by time-lapse cinemicrography in order to determine what factors are responsible for the marked differences in the patterns formed by the two cell lines in culture. Contrary to expectations, both cell types have been found to exhibit contact inhibition of cell locomotion. Therefore, the tendency of 3T3 cells to form monolayers and of Py3T3 cells to form crisscrossed multilayers cannot be explained on the basis of the presence versus the absence of contact inhibition. Morevover, with the exception of cell division control, the social behavior of the two cell types is qualitively similar. Both exhibit cell underlapping and, after contact between lamelliopodia, both show inhibition of locomotory activity and adhesion formation. Neither cell type was observed to migrate over the surface of another cell. The two cell types do show quantitative differences in the frequency of underlapping, the frequency with which contact results in inhibition of locomotion, and the proportion of the cell margin that adheres to the substratum. The increased frequency pf Py3T3 underlapping is correlated with the reduced frequency of substratum adhesions, which in turn favors underlapping. On the basis of these observations, it is concluded that the differences in culture patterns are the result of differences in the shapes of the individual cells, such that underlapping, and hence crisscrossing, is favored in Py3T3 cell interactions and discouraged in 3T3 cells.", "contents": "Locomotory behavior, contact inhibition and pattern formation of 3T3 and polyoma virus-transformed 3T3 cells in culture. The social behavior of 3T3 cells and their polynoma virus-transformed derivative (Py3T3 cells) was examined by time-lapse cinemicrography in order to determine what factors are responsible for the marked differences in the patterns formed by the two cell lines in culture. Contrary to expectations, both cell types have been found to exhibit contact inhibition of cell locomotion. Therefore, the tendency of 3T3 cells to form monolayers and of Py3T3 cells to form crisscrossed multilayers cannot be explained on the basis of the presence versus the absence of contact inhibition. Morevover, with the exception of cell division control, the social behavior of the two cell types is qualitively similar. Both exhibit cell underlapping and, after contact between lamelliopodia, both show inhibition of locomotory activity and adhesion formation. Neither cell type was observed to migrate over the surface of another cell. The two cell types do show quantitative differences in the frequency of underlapping, the frequency with which contact results in inhibition of locomotion, and the proportion of the cell margin that adheres to the substratum. The increased frequency pf Py3T3 underlapping is correlated with the reduced frequency of substratum adhesions, which in turn favors underlapping. On the basis of these observations, it is concluded that the differences in culture patterns are the result of differences in the shapes of the individual cells, such that underlapping, and hence crisscrossing, is favored in Py3T3 cell interactions and discouraged in 3T3 cells."}
{"id": "PMID:198415", "title": "Intracellular protein degradation in growing, in density-inhibited, and in serum-restricted fibroblast cultures.", "content": "Exponentially growing Balb/3T3 mouse fibroblasts contain protein populations with slow and fast turnover. These two stability classes were labelled selectively with 3H-leucine. The intracellular degradation of the proteins was then followed as the release into the medium of radioactive leucine. The degradation rate of both stability classes of protein is increased by about 55% in cultures whose growth is inhibited by high cell density. Serum-deprivation, which also halts cell growth, accelerates protein breakdown to a smaller extent, the increases for relatively stable and unstable proteins being 30% and 13%, respectively. The density-dependent increase in protein breakdown is also found in BHK21 cells but not in chick fibroblasts. Protein degradation in Balb/3T3 cells transformed by simian virus 40 is affected by serum-deprivation but not by cell density. The proteins which are relatively stable during growth were shown to become less stable in density-inhibited or serum-deprived cultures, and vice versa. Cycloheximide inhibits degradation to a variable extent. Dibutyryl adenosine-3',5'-cyclic monophosphate has no effect on the protein degradation under the conditions investigated here.", "contents": "Intracellular protein degradation in growing, in density-inhibited, and in serum-restricted fibroblast cultures. Exponentially growing Balb/3T3 mouse fibroblasts contain protein populations with slow and fast turnover. These two stability classes were labelled selectively with 3H-leucine. The intracellular degradation of the proteins was then followed as the release into the medium of radioactive leucine. The degradation rate of both stability classes of protein is increased by about 55% in cultures whose growth is inhibited by high cell density. Serum-deprivation, which also halts cell growth, accelerates protein breakdown to a smaller extent, the increases for relatively stable and unstable proteins being 30% and 13%, respectively. The density-dependent increase in protein breakdown is also found in BHK21 cells but not in chick fibroblasts. Protein degradation in Balb/3T3 cells transformed by simian virus 40 is affected by serum-deprivation but not by cell density. The proteins which are relatively stable during growth were shown to become less stable in density-inhibited or serum-deprived cultures, and vice versa. Cycloheximide inhibits degradation to a variable extent. Dibutyryl adenosine-3',5'-cyclic monophosphate has no effect on the protein degradation under the conditions investigated here."}
{"id": "PMID:198416", "title": "Coexpression of mutant and wild type protein kinase in lymphoma cells resistant to dibutyryl cyclic AMP.", "content": "A mutant clone resistant to dibutyryl cyclic AMP was isolated from S49 mouse lymphoma cells. The mutant expressed a form of cyclic AMP-dependent protein kinase distinguishable from wild type kinase by its decreased sensitivity to activation by cyclic AMP and its increased thermal lability. Hybrids formed between mutant and wild type cells were resistant to dibutyryl cyclic AMP and expressed both mutant and wild type activities in about equal amount. The parent mutant cells also appeared to express wild type kinase activity, but at a lower level. We conclude that wild type S49 cells have and express two identical alleles for the regulatory subunit of protein kinase, one of which has undergone mutation in the mutant cells.", "contents": "Coexpression of mutant and wild type protein kinase in lymphoma cells resistant to dibutyryl cyclic AMP. A mutant clone resistant to dibutyryl cyclic AMP was isolated from S49 mouse lymphoma cells. The mutant expressed a form of cyclic AMP-dependent protein kinase distinguishable from wild type kinase by its decreased sensitivity to activation by cyclic AMP and its increased thermal lability. Hybrids formed between mutant and wild type cells were resistant to dibutyryl cyclic AMP and expressed both mutant and wild type activities in about equal amount. The parent mutant cells also appeared to express wild type kinase activity, but at a lower level. We conclude that wild type S49 cells have and express two identical alleles for the regulatory subunit of protein kinase, one of which has undergone mutation in the mutant cells."}
{"id": "PMID:198417", "title": "On the regulation of DNA synthesis in a line of adrenocortical tumor cells: effect of serum, adrenocorticotropin and pituitary factors.", "content": "Y-1 adrenal cells responded to serum step down by a several fold decrease in DNA synthesis. Serum starved cells resumed DNA synthesis upon serum step up. ACTH and cAMP inhibited DNA synthesis both at low and high serum concentrations, a fact previously known. Pituitary, brain and liver crude extracts stimulated DNA synthesis in serum starved cells. Purified pituitary factors preparations contained two activities: one specific for Y-1 cells and another active with both fibroblasts and Y-1 cells. The kinetics of restimulation of DNA synthesis by serum and pituitary factors was studied. DNA synthesis restimulation occurred after a lag of 11 hours. This lag did not vary irrespective of the type of stimulator or its concentration. Cells entered S phase continuously at a rate which increased with increasing concentrations of the stimulator. Cells became refractory to the inhibitory action of ACTH five hours before entering S phase. The implications of these data to the understanding of cell growth control are considered.", "contents": "On the regulation of DNA synthesis in a line of adrenocortical tumor cells: effect of serum, adrenocorticotropin and pituitary factors. Y-1 adrenal cells responded to serum step down by a several fold decrease in DNA synthesis. Serum starved cells resumed DNA synthesis upon serum step up. ACTH and cAMP inhibited DNA synthesis both at low and high serum concentrations, a fact previously known. Pituitary, brain and liver crude extracts stimulated DNA synthesis in serum starved cells. Purified pituitary factors preparations contained two activities: one specific for Y-1 cells and another active with both fibroblasts and Y-1 cells. The kinetics of restimulation of DNA synthesis by serum and pituitary factors was studied. DNA synthesis restimulation occurred after a lag of 11 hours. This lag did not vary irrespective of the type of stimulator or its concentration. Cells entered S phase continuously at a rate which increased with increasing concentrations of the stimulator. Cells became refractory to the inhibitory action of ACTH five hours before entering S phase. The implications of these data to the understanding of cell growth control are considered."}
{"id": "PMID:198418", "title": "Transformation of human cystinotic fibroblasts by SV40: characteristics of transformed cells with limited and unlimited growth potential.", "content": "Human skin fibroblasts derived from patients with nephropathic cystinosis were transformed with SV40 virions, cloned and permitted to enter the degenerative stage of growth termed \"crisis,\" characteristic of SV40 transformed human cells. Nephropathic cystinosis is an autosomal recessively inherited metabolic disorder resulting in the intracellular accumulation of the amino acid cystine. A transformed cystinotic cell line which was recovered from the crisis stage was indistinguishable from its transformed precrisis parental cell strain in growth rate in media containing either 1% or 10% serum, cloning efficiency on plastic, in semisolid media, or upon confluent monolayers of normal skin fibroblasts, expression of SV40 T antigen, or production of virus. However, the modal DNA content of the recovered postcrisis transformed cystinotic cell line was different from that of the cloned parental precrisis transformed cell strain, suggesting that the postcrisis line was derived from a small subpopulation of the precrisis strain. The DNA content of the established cystinotic cell line continued to be unstable during subsequent subculturing and gave rise to subclones with both more and less DNA per cell. This line now has an apparently infinite growth potential and still has the hallmark of the cystinotic parental line, the storage of abnormally large amounts of intracellular nonprotein cystine.", "contents": "Transformation of human cystinotic fibroblasts by SV40: characteristics of transformed cells with limited and unlimited growth potential. Human skin fibroblasts derived from patients with nephropathic cystinosis were transformed with SV40 virions, cloned and permitted to enter the degenerative stage of growth termed \"crisis,\" characteristic of SV40 transformed human cells. Nephropathic cystinosis is an autosomal recessively inherited metabolic disorder resulting in the intracellular accumulation of the amino acid cystine. A transformed cystinotic cell line which was recovered from the crisis stage was indistinguishable from its transformed precrisis parental cell strain in growth rate in media containing either 1% or 10% serum, cloning efficiency on plastic, in semisolid media, or upon confluent monolayers of normal skin fibroblasts, expression of SV40 T antigen, or production of virus. However, the modal DNA content of the recovered postcrisis transformed cystinotic cell line was different from that of the cloned parental precrisis transformed cell strain, suggesting that the postcrisis line was derived from a small subpopulation of the precrisis strain. The DNA content of the established cystinotic cell line continued to be unstable during subsequent subculturing and gave rise to subclones with both more and less DNA per cell. This line now has an apparently infinite growth potential and still has the hallmark of the cystinotic parental line, the storage of abnormally large amounts of intracellular nonprotein cystine."}
{"id": "PMID:198419", "title": "Resistance of teratocarcinoma stem cells to infection with simian virus 40: early events.", "content": "Multipotential stem cells of a murine teratocarcinoma are resistant to typical infection with either polyoma virus (PV) or Simian virus 40 (SV40). Differentiated progeny of the stem cells are susceptible to infection in a manner identical to other mouse somatic cells, i.e., they are permissive for PV and nonpermissive for SV40. The early interactions between the stem cells (embryonal carcinoma or EC cells) and SV40 and PV were studied. Virions adsorbed to and penetrated into the cytoplasm and nucleus of EC cells, but did not induce expression of T antigen in the EC nuclei. Purified SV40 DNA was capable of inducing T antigen in differentiated teratocarcinoma cells but not in EC cells. Virus could not be rescued from EC cells previously exposed to SV40. The resistance of the stem cells to infection apparently involves a block in the infectious cycle after adsorption and penetration but before T antigen induction.", "contents": "Resistance of teratocarcinoma stem cells to infection with simian virus 40: early events. Multipotential stem cells of a murine teratocarcinoma are resistant to typical infection with either polyoma virus (PV) or Simian virus 40 (SV40). Differentiated progeny of the stem cells are susceptible to infection in a manner identical to other mouse somatic cells, i.e., they are permissive for PV and nonpermissive for SV40. The early interactions between the stem cells (embryonal carcinoma or EC cells) and SV40 and PV were studied. Virions adsorbed to and penetrated into the cytoplasm and nucleus of EC cells, but did not induce expression of T antigen in the EC nuclei. Purified SV40 DNA was capable of inducing T antigen in differentiated teratocarcinoma cells but not in EC cells. Virus could not be rescued from EC cells previously exposed to SV40. The resistance of the stem cells to infection apparently involves a block in the infectious cycle after adsorption and penetration but before T antigen induction."}
{"id": "PMID:198422", "title": "Estriol conjugates in human breast cyst fluid and in serum of premenopausal women.", "content": "A sensitive method was developed for the assay of the four major estriol (E3) conjugates in human breast cyst fluid and in serum during the menstrual cycle. In the cyst fluid, estriol-3-sulfate (E3-3S) was found in each of ten samples, the concentrations ranging from 240-4310 pg/ml. Estriol-16-glucosiduronate (E3-16G) was detected in six samples at levels of 19-153 pg/ml; estriol-3-glucosiduronate (E3-3G) in five samples, 13-79 pg/ml and estriol-3-sulfate-16-glucosiduronate (E3-3S-16G) in four samples, 28-152 pg/ml. Unconjugated estriol was found in three of the ten cases (12-30 pg/ml). Serum samples obtained in the follicular and luteal phases of the cycle from eight different subjects were assayed in the same way. There was considerable variation between subjects and many values were indistinguishable from zero. But preliminary data suggest that E3-3G is the predominant E3 conjugate in the serum and E3-3S-16G is quantitatively least important. It appears that E3 conjugates in the cyst fluid are not derived from the blood directly, but are produced locally from precursors which have not been identified.", "contents": "Estriol conjugates in human breast cyst fluid and in serum of premenopausal women. A sensitive method was developed for the assay of the four major estriol (E3) conjugates in human breast cyst fluid and in serum during the menstrual cycle. In the cyst fluid, estriol-3-sulfate (E3-3S) was found in each of ten samples, the concentrations ranging from 240-4310 pg/ml. Estriol-16-glucosiduronate (E3-16G) was detected in six samples at levels of 19-153 pg/ml; estriol-3-glucosiduronate (E3-3G) in five samples, 13-79 pg/ml and estriol-3-sulfate-16-glucosiduronate (E3-3S-16G) in four samples, 28-152 pg/ml. Unconjugated estriol was found in three of the ten cases (12-30 pg/ml). Serum samples obtained in the follicular and luteal phases of the cycle from eight different subjects were assayed in the same way. There was considerable variation between subjects and many values were indistinguishable from zero. But preliminary data suggest that E3-3G is the predominant E3 conjugate in the serum and E3-3S-16G is quantitatively least important. It appears that E3 conjugates in the cyst fluid are not derived from the blood directly, but are produced locally from precursors which have not been identified."}
{"id": "PMID:198424", "title": "Reversible gonadotropin deficiency in male Cushing's disease.", "content": "Twelve adult males with documented active Cushing's disease were studied. Mean plasma testosterone (T) was significantly decreased: 1.8 +/- 0.3 (SEM) ng/ml (N=6.8 +/- 0.5); gonadotropin measurements in 8 patients, in basal conditions and under LH-RH iv, showed a significant decrease in both FSH and LH. A further study of 11 patients in remission of Cushing's disease indicated a significant increase in plasma T and gonadotropins up to the normal range. One patient with an initial low T value had a normalized T while in remission, then a dramatic decrease when the disease relapsed. We conclude: a hypogonadotropic hypogonadism is found in male Cushing's disease; it disappears as early as hypercortisolism is suppressed. Some possible mechanisms are discussed.", "contents": "Reversible gonadotropin deficiency in male Cushing's disease. Twelve adult males with documented active Cushing's disease were studied. Mean plasma testosterone (T) was significantly decreased: 1.8 +/- 0.3 (SEM) ng/ml (N=6.8 +/- 0.5); gonadotropin measurements in 8 patients, in basal conditions and under LH-RH iv, showed a significant decrease in both FSH and LH. A further study of 11 patients in remission of Cushing's disease indicated a significant increase in plasma T and gonadotropins up to the normal range. One patient with an initial low T value had a normalized T while in remission, then a dramatic decrease when the disease relapsed. We conclude: a hypogonadotropic hypogonadism is found in male Cushing's disease; it disappears as early as hypercortisolism is suppressed. Some possible mechanisms are discussed."}
{"id": "PMID:198428", "title": "The variations of plasma corticosterone/cortisol ratios following ACTH stimulation or dexamethasone administration in normal men.", "content": "A radioimmunoassay for human plasma corticosterone has been developed. Plasma corticosterone increased 4.83 times as much as basal value at 60 min after an im injection of 0.25 mg synthetic beta1-24 ACTH (Cortrosyn) in normal subjects, whereas plasma cortisol increased 2.12 times as much at 60 min. And basal corticosterone/cortisol ratio of 0.053 +/- 0.017 increased to 0.116 +/- 0.022 (P less than 0.001) after ACTH. This might be mainly due to a larger increment of corticosterone than that of cortisol after ACTH. Corticosterone decreased to 36.7% of basal value at 4 h after 1 mg dexamethasone administration in normal subjects, whereas cortisol decreased to 13.9% of basal value at 4 h. The basal corticosterone/cortisol ratio of 0.059 +/- 0.020 increased to 0.137 +/- 0.055 (0.001 less than P less than 0.01) after dexamethasone administration. This may have been mainly due to a more effective suppression of cortisol than that of corticosterone after dexamethasone.", "contents": "The variations of plasma corticosterone/cortisol ratios following ACTH stimulation or dexamethasone administration in normal men. A radioimmunoassay for human plasma corticosterone has been developed. Plasma corticosterone increased 4.83 times as much as basal value at 60 min after an im injection of 0.25 mg synthetic beta1-24 ACTH (Cortrosyn) in normal subjects, whereas plasma cortisol increased 2.12 times as much at 60 min. And basal corticosterone/cortisol ratio of 0.053 +/- 0.017 increased to 0.116 +/- 0.022 (P less than 0.001) after ACTH. This might be mainly due to a larger increment of corticosterone than that of cortisol after ACTH. Corticosterone decreased to 36.7% of basal value at 4 h after 1 mg dexamethasone administration in normal subjects, whereas cortisol decreased to 13.9% of basal value at 4 h. The basal corticosterone/cortisol ratio of 0.059 +/- 0.020 increased to 0.137 +/- 0.055 (0.001 less than P less than 0.01) after dexamethasone administration. This may have been mainly due to a more effective suppression of cortisol than that of corticosterone after dexamethasone."}
{"id": "PMID:198429", "title": "Center for disease control diagnostic immunology proficiency testing program results for 1976.", "content": "Over 900 laboratories participated in the Diagnostic Immunology portion of the 1976 Proficiency Testing Program, which was provided by the Center of Disease Control under the authority of the Clinical Laboratories Improvement Act of 1967. One hundred specimens prepared by the Center for Disease Control for analysis were distributed on a quarterly schedule or in special surveys. Feedback from participating laboratories included over 37,500 qualitative and 33,000 quantitative responses, which were analyzed to determine individual laboratory proficiency levels. In addition, information supplied by participants in each survey helped to delineate trends in  testing protocols. The specimens chosen for analysis called for a broad range of tests commonly performed in diagnostic immunology laboratories, including those for rubella antibodies, hepatitis B surface antigen, bacterial antibodies, rheumatoid factor, immunoglobulins and other serum-specific proteins, and carcinoembryonic antigen. A summary of the data analysis is provided so that the laboratories can improve their overall performance levels.", "contents": "Center for disease control diagnostic immunology proficiency testing program results for 1976. Over 900 laboratories participated in the Diagnostic Immunology portion of the 1976 Proficiency Testing Program, which was provided by the Center of Disease Control under the authority of the Clinical Laboratories Improvement Act of 1967. One hundred specimens prepared by the Center for Disease Control for analysis were distributed on a quarterly schedule or in special surveys. Feedback from participating laboratories included over 37,500 qualitative and 33,000 quantitative responses, which were analyzed to determine individual laboratory proficiency levels. In addition, information supplied by participants in each survey helped to delineate trends in  testing protocols. The specimens chosen for analysis called for a broad range of tests commonly performed in diagnostic immunology laboratories, including those for rubella antibodies, hepatitis B surface antigen, bacterial antibodies, rheumatoid factor, immunoglobulins and other serum-specific proteins, and carcinoembryonic antigen. A summary of the data analysis is provided so that the laboratories can improve their overall performance levels."}
{"id": "PMID:198430", "title": "Enrichment medium for the isolation of Bordetella.", "content": "The development of a specimen collection and transport medium outfit for the rapid laboratory diagnosis of whoping cough is described. The transport medium consisted of a semisolid agar containing charcoal, cephalexin, and defibrinated horse blood. It was also found to be an excellent enrichment medium for the selective isolation of Bordetella pertussis and B. parapertussis from scantily populated specimens. The investigation of 3,237 specimens that yielded 1,419 positive isolates of Bordetella, including 86 B. parapertussis, during a 20-month period is presented. A total of 3,076 specimens were processed in the laboratory by using the enrichment medium in addition to the routine procedure. Of these specimens, 757 were submitted in our medium, from which 137 (18%) were positive. Of the 567 specimens received in Amies transport medium, 290 (51%) positive cultures were obtained by the enrichment method only and not by primary culture.", "contents": "Enrichment medium for the isolation of Bordetella. The development of a specimen collection and transport medium outfit for the rapid laboratory diagnosis of whoping cough is described. The transport medium consisted of a semisolid agar containing charcoal, cephalexin, and defibrinated horse blood. It was also found to be an excellent enrichment medium for the selective isolation of Bordetella pertussis and B. parapertussis from scantily populated specimens. The investigation of 3,237 specimens that yielded 1,419 positive isolates of Bordetella, including 86 B. parapertussis, during a 20-month period is presented. A total of 3,076 specimens were processed in the laboratory by using the enrichment medium in addition to the routine procedure. Of these specimens, 757 were submitted in our medium, from which 137 (18%) were positive. Of the 567 specimens received in Amies transport medium, 290 (51%) positive cultures were obtained by the enrichment method only and not by primary culture."}
{"id": "PMID:198431", "title": "Characterization of high density lipoproteins in patients heterozygous for Tangier disease.", "content": "In this study a large family group affectd with Tangier disease has been investigated. Besides two homozygous propositi, several heterozygous patients have been identified on the basis of quantitative measurements of high density lipoproteins and their constitutive polypeptides. By a variety of quantitative immunological methods, such as one-dimensional Laurell eletrophoresis, two-dimensional immunoelectrophoresis, and double-antibody radioimmunoassay, the total amount of apoprotein A-I and apoprotein A-I contained in the serum of heterozygous patients and the distribution of these A apoproteins among serum lipoproteins have been determined. The molar ration of apoprotein A-I and apoprotein A-II contained in high density lipoproteins of heterozygous patients did not significantly differ from that of control preparations, although the total mass of high density lipoproteins was reduced by approximately 50%. The elution profile of high density lipoproteins from agarose columns and their morphological appearance, as ascertained by electron microscopy, were similar to control preparations. In addition to the quantitative alterations of serum lipoproteins, lipid storage in histiocytes of the rectal mucosa obtained from heterozygous patients has been documented. It is concluded that patients heterozygous for Tangier disease have normal high density lipoproteins in circulation, the total mass of which is reduced by approximately 50%.", "contents": "Characterization of high density lipoproteins in patients heterozygous for Tangier disease. In this study a large family group affectd with Tangier disease has been investigated. Besides two homozygous propositi, several heterozygous patients have been identified on the basis of quantitative measurements of high density lipoproteins and their constitutive polypeptides. By a variety of quantitative immunological methods, such as one-dimensional Laurell eletrophoresis, two-dimensional immunoelectrophoresis, and double-antibody radioimmunoassay, the total amount of apoprotein A-I and apoprotein A-I contained in the serum of heterozygous patients and the distribution of these A apoproteins among serum lipoproteins have been determined. The molar ration of apoprotein A-I and apoprotein A-II contained in high density lipoproteins of heterozygous patients did not significantly differ from that of control preparations, although the total mass of high density lipoproteins was reduced by approximately 50%. The elution profile of high density lipoproteins from agarose columns and their morphological appearance, as ascertained by electron microscopy, were similar to control preparations. In addition to the quantitative alterations of serum lipoproteins, lipid storage in histiocytes of the rectal mucosa obtained from heterozygous patients has been documented. It is concluded that patients heterozygous for Tangier disease have normal high density lipoproteins in circulation, the total mass of which is reduced by approximately 50%."}
{"id": "PMID:198432", "title": "Collagen-mediated platelet aggregation. Evidence for multivalent interactions of intermediate specificity between collagen and platelets.", "content": "We have shown previously that periodate oxidation of collagen carbohydrate does not affect its ability to aggregate platelets. We now describe an additional characterization of periodate-modified collagen which demonstrates that collagen devoid of intact carbohydrate is fully capable of fibril formation, and we confirm its capacity to initiate platelet aggregation. Furthermore, we demonstrate that the platelet aggregating abilities of Types I, II, and III fibrillar collagen are quite similar despite differences in carbohydrate content and amino acid sequence. We also demonstrate that monomeric, pepsin-solubilized Type I human collagen is ineffective inhibiting aggregation by performed fibrils derived from the same molecule, thus establishing that the affinity of platelets for collagen depends upon prior polymerization of collagen. We interpret these and other findings to demonstrate that the hydroxylysyl glycoside regions of collagen are not highly specific sites involved in platelet-collagen interactions leading to \"physiological\" aggregation, and that the possibility must be considered that multiple interactions involving collagen sites of comparatively low structural specificity may be the initiating events in release of platelet ADP and the ensuing aggregation.", "contents": "Collagen-mediated platelet aggregation. Evidence for multivalent interactions of intermediate specificity between collagen and platelets. We have shown previously that periodate oxidation of collagen carbohydrate does not affect its ability to aggregate platelets. We now describe an additional characterization of periodate-modified collagen which demonstrates that collagen devoid of intact carbohydrate is fully capable of fibril formation, and we confirm its capacity to initiate platelet aggregation. Furthermore, we demonstrate that the platelet aggregating abilities of Types I, II, and III fibrillar collagen are quite similar despite differences in carbohydrate content and amino acid sequence. We also demonstrate that monomeric, pepsin-solubilized Type I human collagen is ineffective inhibiting aggregation by performed fibrils derived from the same molecule, thus establishing that the affinity of platelets for collagen depends upon prior polymerization of collagen. We interpret these and other findings to demonstrate that the hydroxylysyl glycoside regions of collagen are not highly specific sites involved in platelet-collagen interactions leading to \"physiological\" aggregation, and that the possibility must be considered that multiple interactions involving collagen sites of comparatively low structural specificity may be the initiating events in release of platelet ADP and the ensuing aggregation."}
{"id": "PMID:198434", "title": "The biochemical consequences of hypoxia.", "content": "The various phases of energy production have been described. These include glycolysis which is unique in its ability to produce ATP anaerobically, the tricarboxylic acid cycle with its major contribution to ATP production coming through the generation of NADH, and the cytochrome system at which reducing equivalents are converted to water, the released energy being incorporated into high-energy phosphates. The regulation of these pathways has been briefly described and the importance of the small amount of ATP generated anaerobically emphasized. The adaptation of muscle to periods of hypoxia through the presence of myoglobin, creatine phosphate and large amounts of glycogen is then discussed. The role of pH in limiting anaerobic glycolysis in muscle and the importance of the circulation in providing oxygen for exercising muscle are outlined. The effects of hypoxia on certain other tissues such as liver and brain have been detailed and finally methods for assessment of tissue hypoxia in man such as the measurement of the lactate:pyruvate ratio in blood are presented.", "contents": "The biochemical consequences of hypoxia. The various phases of energy production have been described. These include glycolysis which is unique in its ability to produce ATP anaerobically, the tricarboxylic acid cycle with its major contribution to ATP production coming through the generation of NADH, and the cytochrome system at which reducing equivalents are converted to water, the released energy being incorporated into high-energy phosphates. The regulation of these pathways has been briefly described and the importance of the small amount of ATP generated anaerobically emphasized. The adaptation of muscle to periods of hypoxia through the presence of myoglobin, creatine phosphate and large amounts of glycogen is then discussed. The role of pH in limiting anaerobic glycolysis in muscle and the importance of the circulation in providing oxygen for exercising muscle are outlined. The effects of hypoxia on certain other tissues such as liver and brain have been detailed and finally methods for assessment of tissue hypoxia in man such as the measurement of the lactate:pyruvate ratio in blood are presented."}
{"id": "PMID:198441", "title": "A hypothesis concerning the structure of cAMP-and cGMP-dependent protein kinases.", "content": "cAMP-and cGMP-dependent protein kinases have been purified. Each enzyme demonstrates high specificity and affinity for the cyclic nucleotide with binding of two moles of nucleotide per holoenzyme and each enzyme is an ATP: phosphotransferase. The holoenzymes have similar molecular weights and demonstrate similar molecular asymmetry. A structural model relating the two enzymes is proposed. cGMP-dependent protein kinase is proposed to be a dimer composed of two identical protomers in isologous association with the chains arranged in anti-parallel fashion. cAMP-dependent protein kinase is proposed to have a similar structure with a dyad axis of symmetry but with a discontinuity in each chain. These structures account for the differing mechanisms of cyclic nucleotide activation of the two enzymes.", "contents": "A hypothesis concerning the structure of cAMP-and cGMP-dependent protein kinases. cAMP-and cGMP-dependent protein kinases have been purified. Each enzyme demonstrates high specificity and affinity for the cyclic nucleotide with binding of two moles of nucleotide per holoenzyme and each enzyme is an ATP: phosphotransferase. The holoenzymes have similar molecular weights and demonstrate similar molecular asymmetry. A structural model relating the two enzymes is proposed. cGMP-dependent protein kinase is proposed to be a dimer composed of two identical protomers in isologous association with the chains arranged in anti-parallel fashion. cAMP-dependent protein kinase is proposed to have a similar structure with a dyad axis of symmetry but with a discontinuity in each chain. These structures account for the differing mechanisms of cyclic nucleotide activation of the two enzymes."}
{"id": "PMID:198442", "title": "Synchronous generation of ovarian hCG binding sites and LH-sensitive adenylate cyclase in immature rats following treatment with pregnant mare serum gonadotropin.", "content": "A concomitant increase in the activity of LH-senstive adenylate cyclase and in the number of LH/hCG binding sites was induced in ovaries of immature rats upon administration of pregnant mare serum gonadotropin (PMSG), a hormone preparation known to have predominantly follicle stimulation (FSH-like) activity. When an optimal dose of PMSG (15 i.u./rat) was administered to 25-day-old rats, specific activity of LH-dependent adenylate cyclase and the number of binding sites for LH/hCG per mg protein remained unchanged during the first 24h, but 48h after injection a 2-to 4-fold increase in both parameters was observed. By contrast, there was no change in basal adenylate cyclase activity or in the response of the enzyme to the stimulatory action of guanosine-5'-(beta gamma-imino) triphosphate (Gpp (NH)p), GTP, or NaF. Specific activity of succinate cytochrome c reductase, glucose-6-phosphatase and 5'-nucleotidase were found to be unaffected by the hormonal pretreatment, although total protein determined in these homogenates increased 3-fold in the course of this treatment. It is inferred that during follicular maturation, FSH enhances the responsiveness of ovarian adenylate cyclase to LH by stimulating the insertion of LH/hCG-receptors into the cell membrane.", "contents": "Synchronous generation of ovarian hCG binding sites and LH-sensitive adenylate cyclase in immature rats following treatment with pregnant mare serum gonadotropin. A concomitant increase in the activity of LH-senstive adenylate cyclase and in the number of LH/hCG binding sites was induced in ovaries of immature rats upon administration of pregnant mare serum gonadotropin (PMSG), a hormone preparation known to have predominantly follicle stimulation (FSH-like) activity. When an optimal dose of PMSG (15 i.u./rat) was administered to 25-day-old rats, specific activity of LH-dependent adenylate cyclase and the number of binding sites for LH/hCG per mg protein remained unchanged during the first 24h, but 48h after injection a 2-to 4-fold increase in both parameters was observed. By contrast, there was no change in basal adenylate cyclase activity or in the response of the enzyme to the stimulatory action of guanosine-5'-(beta gamma-imino) triphosphate (Gpp (NH)p), GTP, or NaF. Specific activity of succinate cytochrome c reductase, glucose-6-phosphatase and 5'-nucleotidase were found to be unaffected by the hormonal pretreatment, although total protein determined in these homogenates increased 3-fold in the course of this treatment. It is inferred that during follicular maturation, FSH enhances the responsiveness of ovarian adenylate cyclase to LH by stimulating the insertion of LH/hCG-receptors into the cell membrane."}
{"id": "PMID:198443", "title": "Cyclic AMP-protein-DNA complex formation in mammalian cell-free systems.", "content": "A cytoplasmic protein fraction from KB and Chinese hamster ovary cells (CHO-Kl) was shown to bind in vitro to cAMP and subsequently to DNA-cellulose. This protein complex was not found in DE-52 purified CHO-K1 cAMP-dependent protein kinases. The complex appeared to exist as a small fraction of the total cAMP binding proteins, preferred native to denatured DNA and exhibited multiple sedimentation coefficients in glycerol gradients. This complex, after elution from the DNA cellulose column, was shown to have bound specifically to [3H]-cAMP which could be displaced by non-radioactive cAMP in competitive binding assays.", "contents": "Cyclic AMP-protein-DNA complex formation in mammalian cell-free systems. A cytoplasmic protein fraction from KB and Chinese hamster ovary cells (CHO-Kl) was shown to bind in vitro to cAMP and subsequently to DNA-cellulose. This protein complex was not found in DE-52 purified CHO-K1 cAMP-dependent protein kinases. The complex appeared to exist as a small fraction of the total cAMP binding proteins, preferred native to denatured DNA and exhibited multiple sedimentation coefficients in glycerol gradients. This complex, after elution from the DNA cellulose column, was shown to have bound specifically to [3H]-cAMP which could be displaced by non-radioactive cAMP in competitive binding assays."}
{"id": "PMID:198444", "title": "Lack of effect on cyclic GMP content of cells treated with mycophenolic acid.", "content": "Mycophenolic acid, an oncolytic agent and a known inhibitor of guanine ribonucleotide synthesis, has proven to be an effective drug against psoriasis. With reports of greater guantities of c-GMP in psoriatic tissues than in normal tissue, and with the correlation of c-GMP content of cells to proliferation, the effect of mycophenolic acid on cellular c-GMP was investigated. When HeLa, green monkey BSC-1, and mouse L-cells were treated with inhibitory concentrations of mycophenolic acid, no decrease in c-GMP was observed from that of untreated cells. Though mycophenolic acid inhibits guanine ribonucleotide synthesis, this inhibition does not extend to c-GMP synthesis. The inhibition of proliferation of cells by mycophenolic acid then does not include the inhibition of synthesis of c-GMP, but apparently resides solely in limiting the guanylate necessary for nucleic acid synthesis.", "contents": "Lack of effect on cyclic GMP content of cells treated with mycophenolic acid. Mycophenolic acid, an oncolytic agent and a known inhibitor of guanine ribonucleotide synthesis, has proven to be an effective drug against psoriasis. With reports of greater guantities of c-GMP in psoriatic tissues than in normal tissue, and with the correlation of c-GMP content of cells to proliferation, the effect of mycophenolic acid on cellular c-GMP was investigated. When HeLa, green monkey BSC-1, and mouse L-cells were treated with inhibitory concentrations of mycophenolic acid, no decrease in c-GMP was observed from that of untreated cells. Though mycophenolic acid inhibits guanine ribonucleotide synthesis, this inhibition does not extend to c-GMP synthesis. The inhibition of proliferation of cells by mycophenolic acid then does not include the inhibition of synthesis of c-GMP, but apparently resides solely in limiting the guanylate necessary for nucleic acid synthesis."}
{"id": "PMID:198445", "title": "Phosphorylation of casein by the lactating mammary gland: a review.", "content": "The lactating mammary gland synthesizes and secretes large amounts of phosphoproteins that mainly are associated with the casein fraction of milk. The free amino acids and inorganic phosphate of blood serve as building materials for casein, and the final product appears in milk as a colloidal-sized particle, the casein micelle. According to our present concept, the biosynthesis of casein occurs in two steps: synthesis of the polypeptide chain, followed by phosphate addition. Phosphate groups are transferred to the nascent casein by a protein kinase localized in the Golgi apparatus. The enzyme uses adenosine 5'-triphosphate as the phosphate donor and requires divalent cations. Neighboring amino acids may be important in determining which serine residues in casein are phosphorylated. This review discusses historical and current research on the phosphorylation of casein.", "contents": "Phosphorylation of casein by the lactating mammary gland: a review. The lactating mammary gland synthesizes and secretes large amounts of phosphoproteins that mainly are associated with the casein fraction of milk. The free amino acids and inorganic phosphate of blood serve as building materials for casein, and the final product appears in milk as a colloidal-sized particle, the casein micelle. According to our present concept, the biosynthesis of casein occurs in two steps: synthesis of the polypeptide chain, followed by phosphate addition. Phosphate groups are transferred to the nascent casein by a protein kinase localized in the Golgi apparatus. The enzyme uses adenosine 5'-triphosphate as the phosphate donor and requires divalent cations. Neighboring amino acids may be important in determining which serine residues in casein are phosphorylated. This review discusses historical and current research on the phosphorylation of casein."}
{"id": "PMID:198446", "title": "Effects of polybrominated biphenyls on health and performance of pregnant Holstein heifers.", "content": "The toxicity of a commercial blend of polybrominated biphenyls was determined in 24 pregnant Holstein heifers that were allotted randomly to one of four experimental groups given 0, .25, 250, or 25,000 mg/day of fire-Master BP-6. The polybrominated biphenyls were mixed with finely ground corn and given by bolus for 60 days or until the animal became moribund. Average body weight of heifers at onset of experiment was 381 kg. No clinical signs of toxicosis were evident in heifers fed 0, .25 or 250 mg/day. Toxicosis was induced in heifers fed 25,000 mg/day resulting in reduced dry matter intake, body weight, heart rate, and respiration rate. Clinical signs were anorexia, emaciation, dehydration, excessive lacrimation and salivation, diarrhea, depression, and abortion or fetal death. All heifers fed 25,000 mg/day became moribund within 33 to 66 days.", "contents": "Effects of polybrominated biphenyls on health and performance of pregnant Holstein heifers. The toxicity of a commercial blend of polybrominated biphenyls was determined in 24 pregnant Holstein heifers that were allotted randomly to one of four experimental groups given 0, .25, 250, or 25,000 mg/day of fire-Master BP-6. The polybrominated biphenyls were mixed with finely ground corn and given by bolus for 60 days or until the animal became moribund. Average body weight of heifers at onset of experiment was 381 kg. No clinical signs of toxicosis were evident in heifers fed 0, .25 or 250 mg/day. Toxicosis was induced in heifers fed 25,000 mg/day resulting in reduced dry matter intake, body weight, heart rate, and respiration rate. Clinical signs were anorexia, emaciation, dehydration, excessive lacrimation and salivation, diarrhea, depression, and abortion or fetal death. All heifers fed 25,000 mg/day became moribund within 33 to 66 days."}
{"id": "PMID:198448", "title": "Myocardial uptake of Tc-99m skeletal agents in the rat after experimental induction of microscopic foci of injury.", "content": "The cardiac uptake of Tc-99m tagged skeletal agents was studied after myocardial injury produced by subcutaneous catecholamine injection and random foot-shock stress. Rats stressed for 2 hr developed microfocal myocardial injury, without gross change, whereas those stressed for 12 hr sustained more confluent and sometimes grossly visible damage. Tc-99m MDP and Tc-99m PPi concentrations in these hearts were significantly above control (undamaged) heart levels, producing positive gamma-camera images. Subcutaneous epinephrine injections resulted in grossly visible lesions, with tracer concentrations higher than those previously reported in vasoocclusive infarcts. We postulate that the stress-induced scattered microfocal lesions may accumulate radiopharmaceutical on a per-gram basis in the same way as the larger catecholamine-induced lesions, since tracer delivery to the injured areas in each case is probably less impeded than in frankly vasoocclusive models. Such microfoci, then, could provide an explanation for some of the \"false positive\" myocardial scans observed clinically.", "contents": "Myocardial uptake of Tc-99m skeletal agents in the rat after experimental induction of microscopic foci of injury. The cardiac uptake of Tc-99m tagged skeletal agents was studied after myocardial injury produced by subcutaneous catecholamine injection and random foot-shock stress. Rats stressed for 2 hr developed microfocal myocardial injury, without gross change, whereas those stressed for 12 hr sustained more confluent and sometimes grossly visible damage. Tc-99m MDP and Tc-99m PPi concentrations in these hearts were significantly above control (undamaged) heart levels, producing positive gamma-camera images. Subcutaneous epinephrine injections resulted in grossly visible lesions, with tracer concentrations higher than those previously reported in vasoocclusive infarcts. We postulate that the stress-induced scattered microfocal lesions may accumulate radiopharmaceutical on a per-gram basis in the same way as the larger catecholamine-induced lesions, since tracer delivery to the injured areas in each case is probably less impeded than in frankly vasoocclusive models. Such microfoci, then, could provide an explanation for some of the \"false positive\" myocardial scans observed clinically."}
{"id": "PMID:198449", "title": "Cochlear micromechanics--a mechanism for transforming mechanical to neural tuning within the cochlea.", "content": "A linear mathematical model is proposed which will account for the differences observed between mechanically measured data of Rhode (1971) for basilar membrane motion, and the responses of neural tuning curves (Kiang et al., 1974). We show that theoretical tuning curves may be derived from mechanical responses by forming the difference between the pressure across the basilar membrane and its displacement. Some ramifications of this proposal are discussed. We then propose a hypothetical physical model which could perform such a function.", "contents": "Cochlear micromechanics--a mechanism for transforming mechanical to neural tuning within the cochlea. A linear mathematical model is proposed which will account for the differences observed between mechanically measured data of Rhode (1971) for basilar membrane motion, and the responses of neural tuning curves (Kiang et al., 1974). We show that theoretical tuning curves may be derived from mechanical responses by forming the difference between the pressure across the basilar membrane and its displacement. Some ramifications of this proposal are discussed. We then propose a hypothetical physical model which could perform such a function."}
{"id": "PMID:198451", "title": "The in vitro effect of toluene diisocyanate on lymphocyte cyclic adenosine monophosphate production by isoproterenol, prostaglandin, and histamine: a possible mode of action.", "content": "Toluene diisocyanate (TDI) significantly inhibits the rise in intracellular cyclic 3',5'-adenosine monophosphate (cAMP) that follows in vitro incubation of human lymphocytes with 6.7 x 10(-3) M isoproterenol and 1 x 10(-6) M prostagladin E1 (p less than 0.05). TDI has no significant effect on th production of lymphocyte cAMP following incubation with histamine (1 x 10(-3) M). The inhibitory action of TDI is greatest at a concentration of 3.3 x 10(-4) M and diminishes as the TDI concentration is increased or decreased. TDI also caused four- to fivefold stimulation of lymphocyte cAMP, an effect that is maximal at 1 x 10(-3) M, a concentration which has no significant inhibitory effect on stimulation of cAMP by isoproterenol or prostagladin E1. Conversely, 3.3 x 10(-4) M TDI, which inhibits cAMP production by isoproterenol and prostaglandin, has little stimulatory effect itself on cAMP production. This evidence suggests that TDI might induce obstructive airways disease through pharmacologic mechanisms and that TDI may be acting as a partial agonist.", "contents": "The in vitro effect of toluene diisocyanate on lymphocyte cyclic adenosine monophosphate production by isoproterenol, prostaglandin, and histamine: a possible mode of action. Toluene diisocyanate (TDI) significantly inhibits the rise in intracellular cyclic 3',5'-adenosine monophosphate (cAMP) that follows in vitro incubation of human lymphocytes with 6.7 x 10(-3) M isoproterenol and 1 x 10(-6) M prostagladin E1 (p less than 0.05). TDI has no significant effect on th production of lymphocyte cAMP following incubation with histamine (1 x 10(-3) M). The inhibitory action of TDI is greatest at a concentration of 3.3 x 10(-4) M and diminishes as the TDI concentration is increased or decreased. TDI also caused four- to fivefold stimulation of lymphocyte cAMP, an effect that is maximal at 1 x 10(-3) M, a concentration which has no significant inhibitory effect on stimulation of cAMP by isoproterenol or prostagladin E1. Conversely, 3.3 x 10(-4) M TDI, which inhibits cAMP production by isoproterenol and prostaglandin, has little stimulatory effect itself on cAMP production. This evidence suggests that TDI might induce obstructive airways disease through pharmacologic mechanisms and that TDI may be acting as a partial agonist."}
{"id": "PMID:198452", "title": "Drug-induced changes of adenylate cyclase activity in cells from asthmatic and nonasthmatic subjects.", "content": "Monolayers of adherent mononuclear leukocytes prepared from normal subjects and asthmatic children whose bronchodilater therapy did not include sympathomimetic drugs, respond to relatively low concentrations of isoproterenol (ISO) and prostaglandin E1 with increased intracellular cyclic adenosine monophosphate (cAMP) levels. The magnitude of in vitro responses to ISO is decreased by previous contact of the cells with ISO or other, orally effective, adrenergic drugs. The desensitization is rapid, concentration- and time-dependent, and is readily reversible after removal of the desensitizing drug. The phenomenon exhibits pharmacologic specificity. Cells in which the response to restimulation with ISO was decreased exhibited full sensitivity to prostaglandin E1. No differences in these behaviors were detected in cells from normal or asthmatic subjects. The results suggest that earlier observations reporting decreased responses to beta adrenergic stimulation in asthmatics may have been due to the treatment of these patients with sympathomimetic agents and not caused by a disease-related beta adrenergic receptor dysfunction.", "contents": "Drug-induced changes of adenylate cyclase activity in cells from asthmatic and nonasthmatic subjects. Monolayers of adherent mononuclear leukocytes prepared from normal subjects and asthmatic children whose bronchodilater therapy did not include sympathomimetic drugs, respond to relatively low concentrations of isoproterenol (ISO) and prostaglandin E1 with increased intracellular cyclic adenosine monophosphate (cAMP) levels. The magnitude of in vitro responses to ISO is decreased by previous contact of the cells with ISO or other, orally effective, adrenergic drugs. The desensitization is rapid, concentration- and time-dependent, and is readily reversible after removal of the desensitizing drug. The phenomenon exhibits pharmacologic specificity. Cells in which the response to restimulation with ISO was decreased exhibited full sensitivity to prostaglandin E1. No differences in these behaviors were detected in cells from normal or asthmatic subjects. The results suggest that earlier observations reporting decreased responses to beta adrenergic stimulation in asthmatics may have been due to the treatment of these patients with sympathomimetic agents and not caused by a disease-related beta adrenergic receptor dysfunction."}
{"id": "PMID:198453", "title": "Depression in the aged: theoretical concepts.", "content": "The etiology of depression in the aged is discussed from the viewpoint of biologic, psychodynamic, genetic and sociocultural concepts. The chronic neurotic depression of the aged seems to differ from that of younger age groups. The understanding of geriatric depression requires a multidisciplinary approach.", "contents": "Depression in the aged: theoretical concepts. The etiology of depression in the aged is discussed from the viewpoint of biologic, psychodynamic, genetic and sociocultural concepts. The chronic neurotic depression of the aged seems to differ from that of younger age groups. The understanding of geriatric depression requires a multidisciplinary approach."}
{"id": "PMID:198459", "title": "Surgical management of brachial plexus injuries.", "content": "Exploration of the brachial plexus was done as an elective procedure in 56 patients with complete or partial lesions. The indications were based on clinical findings, a Tinel-Hoffman sign indicating that at least one root was available for direct repair, or a cessation of signs of progressive recovery. In young patients with supraganglionic lesions and evidence of root avulsion, nerve grafts from intercostals to various portions of the plexus were done. Evaluation of the results of motor functions showed that 38 of 54 (70 percent) recovered a useful motor function in at least one important area. There were two postoperative hematomas leading to delayed healing and failure of nerve recovery. Two patients had temporary loss of power in uninvolved muscles but both recovered satisfactory function. Only one patient had a persistent pain syndrome. Two failures were due to the late operation (19 months after injury) and one because of a 15 cm. which was grafted.", "contents": "Surgical management of brachial plexus injuries. Exploration of the brachial plexus was done as an elective procedure in 56 patients with complete or partial lesions. The indications were based on clinical findings, a Tinel-Hoffman sign indicating that at least one root was available for direct repair, or a cessation of signs of progressive recovery. In young patients with supraganglionic lesions and evidence of root avulsion, nerve grafts from intercostals to various portions of the plexus were done. Evaluation of the results of motor functions showed that 38 of 54 (70 percent) recovered a useful motor function in at least one important area. There were two postoperative hematomas leading to delayed healing and failure of nerve recovery. Two patients had temporary loss of power in uninvolved muscles but both recovered satisfactory function. Only one patient had a persistent pain syndrome. Two failures were due to the late operation (19 months after injury) and one because of a 15 cm. which was grafted."}
{"id": "PMID:198460", "title": "Peripheral neuropathy--an unusual complication of meningococcemia.", "content": "A case of meningococcemia with a persisting peripheral neuropathy and gangrene of the fingers is presented. These unusual complications are thought to be related to the diffuse intravascular coagulation syndrome.", "contents": "Peripheral neuropathy--an unusual complication of meningococcemia. A case of meningococcemia with a persisting peripheral neuropathy and gangrene of the fingers is presented. These unusual complications are thought to be related to the diffuse intravascular coagulation syndrome."}
{"id": "PMID:198476", "title": "Analysis of murine C-type virus structural proteins by rocket and crossed immunoelectrophoresis.", "content": "We have examined the structural proteins of Rauscher murine leukemia virus (R-MuLV) by means of rocket immunoelectrophoresis and crossed immunoelectrophoresis, using polyspecific antisera to Tween/ether-disrupted purified R-MuLV. Fifteen different precipitation lines were recognized in virus lysates. Using five reference antisera prepared to purified R-MuLV-structural proteins, the precipitation lines of p 10, p 15, p 30 and gp 69/70 were identified. These techniques, although less sensitive than radioimmunoassay, have several advantages, such as simplicity, direct control of precipitation reactions and possibility of using crude antigen preparations.", "contents": "Analysis of murine C-type virus structural proteins by rocket and crossed immunoelectrophoresis. We have examined the structural proteins of Rauscher murine leukemia virus (R-MuLV) by means of rocket immunoelectrophoresis and crossed immunoelectrophoresis, using polyspecific antisera to Tween/ether-disrupted purified R-MuLV. Fifteen different precipitation lines were recognized in virus lysates. Using five reference antisera prepared to purified R-MuLV-structural proteins, the precipitation lines of p 10, p 15, p 30 and gp 69/70 were identified. These techniques, although less sensitive than radioimmunoassay, have several advantages, such as simplicity, direct control of precipitation reactions and possibility of using crude antigen preparations."}
{"id": "PMID:198477", "title": "A rapid microassay for detecting antibodies against poliovirus based on [14C]thymidine uptake of treated cell cultures.", "content": "DNA synthesis of mammalian cells propagated in microplates can easily be measured if cell cultures incubated with [14C]thymidine are harvested on the glass fibre filters by a semiautomatic harvesting technique. Soon after infection with poliovirus, [14C]thymidine uptake of U cells (established, human amniotic cell line) is inhibited. This inhibition can be prevented by previous virus neutralization with antibody. Based on this effect a rapid, precise assay method was set up to determine neutralizing antibody titres against poliovirus. There was a good correlation between titres obtained by this assay and those obtained by 50% end point titrations in cytopathogenic effect inhibition assays.", "contents": "A rapid microassay for detecting antibodies against poliovirus based on [14C]thymidine uptake of treated cell cultures. DNA synthesis of mammalian cells propagated in microplates can easily be measured if cell cultures incubated with [14C]thymidine are harvested on the glass fibre filters by a semiautomatic harvesting technique. Soon after infection with poliovirus, [14C]thymidine uptake of U cells (established, human amniotic cell line) is inhibited. This inhibition can be prevented by previous virus neutralization with antibody. Based on this effect a rapid, precise assay method was set up to determine neutralizing antibody titres against poliovirus. There was a good correlation between titres obtained by this assay and those obtained by 50% end point titrations in cytopathogenic effect inhibition assays."}
{"id": "PMID:198478", "title": "Quantitation and immunocytochemical localization of human skin collagenase in basal cell carcinoma.", "content": "Human skin collagenase was quantitated by radioimmunoassay in 21 basal cell carcinomas. Immunoreactive collagenase protein was found to be approximately 2-fold greater in extracts of these tumors than in extracts of normal skin, suggesting that this enzyme may be important in the pathogenesis of soft tissue destruction in vivo. To further define the role of collagenase in such destruction, immunofluorescent staining with specific antiserum to human skin collagenase was used to localize collagenase in the basal cell carcinomas. The enzyme was found only in the stromal elements surrounding the tumor islands. No staining of the epithelial components of the basal cell carcinomas was found. These findings suggest that the normal connective tissue elements may have been stimulated to produce an increased amount of collagenase and emphasize the importance of epithelial-stromal interaction in soft tissue invasiveness.", "contents": "Quantitation and immunocytochemical localization of human skin collagenase in basal cell carcinoma. Human skin collagenase was quantitated by radioimmunoassay in 21 basal cell carcinomas. Immunoreactive collagenase protein was found to be approximately 2-fold greater in extracts of these tumors than in extracts of normal skin, suggesting that this enzyme may be important in the pathogenesis of soft tissue destruction in vivo. To further define the role of collagenase in such destruction, immunofluorescent staining with specific antiserum to human skin collagenase was used to localize collagenase in the basal cell carcinomas. The enzyme was found only in the stromal elements surrounding the tumor islands. No staining of the epithelial components of the basal cell carcinomas was found. These findings suggest that the normal connective tissue elements may have been stimulated to produce an increased amount of collagenase and emphasize the importance of epithelial-stromal interaction in soft tissue invasiveness."}
{"id": "PMID:198479", "title": "Characterization of cryoprecipitates in pemphigus: demonstration of pemphigus antibody activity in cryoprecipitates using the immunofluorescent technique.", "content": "Cryoproteins observed in patients with pemphigus have been shown to contain IgG, complement components, and other serum proteins. The IgG moiety possessed pemphigus antibody activity and contained kappa and lambda light chains. Cryoproteins appeared in the clinically active stage and disappeared subsequent to clinical improvement. These observations indicate that immune complexes may exist in the sera of patients with pemphigus.", "contents": "Characterization of cryoprecipitates in pemphigus: demonstration of pemphigus antibody activity in cryoprecipitates using the immunofluorescent technique. Cryoproteins observed in patients with pemphigus have been shown to contain IgG, complement components, and other serum proteins. The IgG moiety possessed pemphigus antibody activity and contained kappa and lambda light chains. Cryoproteins appeared in the clinically active stage and disappeared subsequent to clinical improvement. These observations indicate that immune complexes may exist in the sera of patients with pemphigus."}
{"id": "PMID:198480", "title": "Epidermal adenylate cyclase: stimulation of the histamine (H2) receptor by tolazoline.", "content": "Tolazoline (2-benzyl-2-imidazoline) activated adenylate cyclase in pig epidermal slices resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of the cyclic AMP-phosphodiesterase inhibitor, theophylline. Specific histamine (H2) receptor inhibitors (metiamide and cimetidine) completely blocked the tolazoline activation of adenylate cylase. At low concentrations (10-100 micrometer), a histamine (H1) receptor inhibitor (diphenhydramine) and a beta-adrenergic blocker (propranolol) did not inhibit this effect. The stimulation of cyclic AMP formation by the combination of tolazoline and histamine was about the same as the stimulation by histamine alone (nonadditive), whereas the stimulatory effects by tolazoline and epinephrine were additive. These data suggest that tolazoline, an alpha-adrenergic blocker, also activates adenylate cyclase at the histamine (H2) receptor site which is distinct from the beta-adrenergic receptor site. Another alpha-adrenergic blocker, phentolamine, did not have this effect.", "contents": "Epidermal adenylate cyclase: stimulation of the histamine (H2) receptor by tolazoline. Tolazoline (2-benzyl-2-imidazoline) activated adenylate cyclase in pig epidermal slices resulting in the accumulation of cyclic AMP. This effect was highly potentiated by the addition of the cyclic AMP-phosphodiesterase inhibitor, theophylline. Specific histamine (H2) receptor inhibitors (metiamide and cimetidine) completely blocked the tolazoline activation of adenylate cylase. At low concentrations (10-100 micrometer), a histamine (H1) receptor inhibitor (diphenhydramine) and a beta-adrenergic blocker (propranolol) did not inhibit this effect. The stimulation of cyclic AMP formation by the combination of tolazoline and histamine was about the same as the stimulation by histamine alone (nonadditive), whereas the stimulatory effects by tolazoline and epinephrine were additive. These data suggest that tolazoline, an alpha-adrenergic blocker, also activates adenylate cyclase at the histamine (H2) receptor site which is distinct from the beta-adrenergic receptor site. Another alpha-adrenergic blocker, phentolamine, did not have this effect."}
{"id": "PMID:198483", "title": "Murine cytomegalovirus infection of epithelial cells in mouse tracheal ring organ culture.", "content": "A differentiated tissue model was used to study the course of cytomegalovirus infection in respiratory epithelium in vitro. Mouse tracheal rings in organ culture were infected with murine cytomegalovirus. Infectious virus in the medium reached average titers of 10(5.5) plaque-forming units/ml by day 17. Infected epithelial cells on the rings contained viral antigen as demonstrated by immunofluorescence staining; light microscopy of these cells revealed enlarged nuclei, cytoplasmic vacuolization, and nuclear and cytoplasmic inclusions characteristic of infection with cytomegalo-virus. Development of viral particles, as visualized by electron microscopy, was similar to that observed in other types of cells.", "contents": "Murine cytomegalovirus infection of epithelial cells in mouse tracheal ring organ culture. A differentiated tissue model was used to study the course of cytomegalovirus infection in respiratory epithelium in vitro. Mouse tracheal rings in organ culture were infected with murine cytomegalovirus. Infectious virus in the medium reached average titers of 10(5.5) plaque-forming units/ml by day 17. Infected epithelial cells on the rings contained viral antigen as demonstrated by immunofluorescence staining; light microscopy of these cells revealed enlarged nuclei, cytoplasmic vacuolization, and nuclear and cytoplasmic inclusions characteristic of infection with cytomegalo-virus. Development of viral particles, as visualized by electron microscopy, was similar to that observed in other types of cells."}
{"id": "PMID:198485", "title": "Inhibition of the biologic effects of endotoxin on neutrophils by polymyxin B sulfate.", "content": "Polymyxin B sulfate diminished the endotoxin-mediated release of human blood neutrophil lysosomal enzymes. Similarly, this antibiotic reduced the endotoxin-induced increase in the neutrophil hexose monophosphate pathway activity as measured by the release of 14CO2 from [l-14C]glucose. Although these effects were seen with therapeutically attainable levels of polymyxin B sulfate, they could not be demonstrated when the cell-endotoxin interaction preceded treatment with polymyxin B sulfate.", "contents": "Inhibition of the biologic effects of endotoxin on neutrophils by polymyxin B sulfate. Polymyxin B sulfate diminished the endotoxin-mediated release of human blood neutrophil lysosomal enzymes. Similarly, this antibiotic reduced the endotoxin-induced increase in the neutrophil hexose monophosphate pathway activity as measured by the release of 14CO2 from [l-14C]glucose. Although these effects were seen with therapeutically attainable levels of polymyxin B sulfate, they could not be demonstrated when the cell-endotoxin interaction preceded treatment with polymyxin B sulfate."}
{"id": "PMID:198486", "title": "Free amino acids in plasma during experimental infection of mice with the MHV-3 strain of mouse hepatitis virus.", "content": "The concentrations of total free amino acids, single free amino acids, urea, and ammonia were determined in plasma of mice during experimental infection with the MHV-3 strain of mouse hepatitis virus. Analysis of free amino acids was done by ion-exchange resin chromatography under conditions that allowed the use of a single chromatographic column, separation of glutamine and asparagine, and an accelerated rate of chromatography. The results showed that as early as 6 hr after infection there was a decrease in the concentration of several free amino acids as well as in the total concentration of free amino acids in plasma. For most of the amino acids the decrease persisted until 48 hr. Only at 72 hr, during severe cytolysis, did the concentration of amino acids increase significantly. It is suggested that the decrease during the initial phases of the infection may be due to a thermolabile factor that is produced by circulating leukocytes and that effects a flow of free amino acids from the plasma toward the liver. The final increase in concentration of several free amino acids reflects the cytolytic damage to the liver caused by the virus.", "contents": "Free amino acids in plasma during experimental infection of mice with the MHV-3 strain of mouse hepatitis virus. The concentrations of total free amino acids, single free amino acids, urea, and ammonia were determined in plasma of mice during experimental infection with the MHV-3 strain of mouse hepatitis virus. Analysis of free amino acids was done by ion-exchange resin chromatography under conditions that allowed the use of a single chromatographic column, separation of glutamine and asparagine, and an accelerated rate of chromatography. The results showed that as early as 6 hr after infection there was a decrease in the concentration of several free amino acids as well as in the total concentration of free amino acids in plasma. For most of the amino acids the decrease persisted until 48 hr. Only at 72 hr, during severe cytolysis, did the concentration of amino acids increase significantly. It is suggested that the decrease during the initial phases of the infection may be due to a thermolabile factor that is produced by circulating leukocytes and that effects a flow of free amino acids from the plasma toward the liver. The final increase in concentration of several free amino acids reflects the cytolytic damage to the liver caused by the virus."}
{"id": "PMID:198487", "title": "Antibody to varicella-zoster virus-induced membrane antigen: immunofluorescence assay using monodisperse glutaraldehyde-fixed target cells.", "content": "A sensitive and reproducible technique was developed for the detection of antibody to varicella-zoster virus-induced membrane antigen (VZMA) by immunofluorescence. Controlled trypsinization and glutaraldehyde fixation were employed to prepare a monodisperse suspension of noninfectious VZMA-positive target cells that can be stored indefinitely at -72 degrees C. A microtiter immunofluorescence assay utilizing these target cells was shown to provide a sensitive and specific means for the detection and quantitation of antibody to varicella-zoster virus. The properties of the target cell preparation and the characteristics of the assay make practical the rapid assessment of immunity to the varicella-zoster virus.", "contents": "Antibody to varicella-zoster virus-induced membrane antigen: immunofluorescence assay using monodisperse glutaraldehyde-fixed target cells. A sensitive and reproducible technique was developed for the detection of antibody to varicella-zoster virus-induced membrane antigen (VZMA) by immunofluorescence. Controlled trypsinization and glutaraldehyde fixation were employed to prepare a monodisperse suspension of noninfectious VZMA-positive target cells that can be stored indefinitely at -72 degrees C. A microtiter immunofluorescence assay utilizing these target cells was shown to provide a sensitive and specific means for the detection and quantitation of antibody to varicella-zoster virus. The properties of the target cell preparation and the characteristics of the assay make practical the rapid assessment of immunity to the varicella-zoster virus."}
{"id": "PMID:198488", "title": "Prospective study of prevalence, incidence, and source of herpesvirus infections in patients with renal allografts.", "content": "The prevalence, incidence, and source of infections with different types of herpesviruses were determined prospectively for 25 persons undergoing hemodialysis, 30 allograft recipients, and 16 kidney donors. The prevalence of prior infections with cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) was high (72%-100%) and was similar for healthy persons and those with renal failure. The incidence of infections in patients undergoing hemodialysis was no greater than that before dialysis. In allograft recipients, the incidence of infection with CMV was 73%; HSV, 57%; EBV, 30%; and varicella-zoster virus (clinical), 7%. Ninety-seven percent of the patients developed an infection with one or more herpesviruses. Transfusions, hemodialysis, the allograft, and hospital environment were not significant sources in transmission. Uremia and splenectomy were unimportant in the reactivation of infection. Immunosuppressive drugs possibly algmented by a graft rejection response account for the high incidence of recrudescent infections with CMV and HSV.", "contents": "Prospective study of prevalence, incidence, and source of herpesvirus infections in patients with renal allografts. The prevalence, incidence, and source of infections with different types of herpesviruses were determined prospectively for 25 persons undergoing hemodialysis, 30 allograft recipients, and 16 kidney donors. The prevalence of prior infections with cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) was high (72%-100%) and was similar for healthy persons and those with renal failure. The incidence of infections in patients undergoing hemodialysis was no greater than that before dialysis. In allograft recipients, the incidence of infection with CMV was 73%; HSV, 57%; EBV, 30%; and varicella-zoster virus (clinical), 7%. Ninety-seven percent of the patients developed an infection with one or more herpesviruses. Transfusions, hemodialysis, the allograft, and hospital environment were not significant sources in transmission. Uremia and splenectomy were unimportant in the reactivation of infection. Immunosuppressive drugs possibly algmented by a graft rejection response account for the high incidence of recrudescent infections with CMV and HSV."}
{"id": "PMID:198489", "title": "Isolation of simian virus 40 from rhesus monkeys (Macaca mulatta) with spontaneous progressive multifocal leukoencephalopathy.", "content": "Isolates of virus from the brain tissue of two naturally occurring cases of progressive multifocal leukoencephalopathy in rhesus monkeys (Macaca mulatta) have been characterized. Both isolates were demonstrated to be simian virus 40 (SV40) by serological tests and analysis of cleavage fragments of viral deoxyribonucleic acid produced by restriction endonuclease from Haemophilus influenzae. SV40 virions and the nonvirion T antigen were demonstrated in the brain lesions of one monkey by the fluorescent antibody staining technique. SV40 was not demonstrated in the brain of normal rhesus monkeys from the same colony with use of the same methods of viral isolation or demonstration of antigen.", "contents": "Isolation of simian virus 40 from rhesus monkeys (Macaca mulatta) with spontaneous progressive multifocal leukoencephalopathy. Isolates of virus from the brain tissue of two naturally occurring cases of progressive multifocal leukoencephalopathy in rhesus monkeys (Macaca mulatta) have been characterized. Both isolates were demonstrated to be simian virus 40 (SV40) by serological tests and analysis of cleavage fragments of viral deoxyribonucleic acid produced by restriction endonuclease from Haemophilus influenzae. SV40 virions and the nonvirion T antigen were demonstrated in the brain lesions of one monkey by the fluorescent antibody staining technique. SV40 was not demonstrated in the brain of normal rhesus monkeys from the same colony with use of the same methods of viral isolation or demonstration of antigen."}
{"id": "PMID:198490", "title": "Enzyme immunoassays for viral diseases.", "content": "Microplate enzyme-linked immunosorbent assays (ELISA) for viral diseases were investigated with special reference to rubella. Standardization of the carrier plates, antigens, conjugates, and substrate was found to be essential. The ELISA results were compared with results of hemagglutination-inhibition tests for rubella, and ELISA was used in an epidemiologic study. Antibodies to cytomegalovirus, measles, adenovirus, coxsackieviruses, and herpesviruses were also assayed by ELISA. ELISA has veterinary applications in detection of respiratory syncytial virus and Newcastle disease virus, and it has been used for assay of plant viruses.", "contents": "Enzyme immunoassays for viral diseases. Microplate enzyme-linked immunosorbent assays (ELISA) for viral diseases were investigated with special reference to rubella. Standardization of the carrier plates, antigens, conjugates, and substrate was found to be essential. The ELISA results were compared with results of hemagglutination-inhibition tests for rubella, and ELISA was used in an epidemiologic study. Antibodies to cytomegalovirus, measles, adenovirus, coxsackieviruses, and herpesviruses were also assayed by ELISA. ELISA has veterinary applications in detection of respiratory syncytial virus and Newcastle disease virus, and it has been used for assay of plant viruses."}
{"id": "PMID:198491", "title": "Detection of antibodies specific for herpes simplex virus in human sera by the enzyme-linked immunosorbent assay.", "content": "An enzyme-linked immunosorbent assay (ELISA) was used for the detection in human sera of antibody to herpes simplex virus antigens. Development and standardization of the assay suggested that antigenic purity, temperature of reactions, concentration of enzyme-conjugated antiglobulin, and concentrations of test sera are all critical parameters of a successful ELISA procedure. When ELISA titers of 30 human sera were compared to micro-complement fixation titers of the same sera, a significant degree of correlation was observed, but quantitatively ELISA was found to be up to 200 times more sensitive. The sensitivity of the assay and its adaptability to automation should provide an additional method for study or diagnosis of infection with herpes simplex virus.", "contents": "Detection of antibodies specific for herpes simplex virus in human sera by the enzyme-linked immunosorbent assay. An enzyme-linked immunosorbent assay (ELISA) was used for the detection in human sera of antibody to herpes simplex virus antigens. Development and standardization of the assay suggested that antigenic purity, temperature of reactions, concentration of enzyme-conjugated antiglobulin, and concentrations of test sera are all critical parameters of a successful ELISA procedure. When ELISA titers of 30 human sera were compared to micro-complement fixation titers of the same sera, a significant degree of correlation was observed, but quantitatively ELISA was found to be up to 200 times more sensitive. The sensitivity of the assay and its adaptability to automation should provide an additional method for study or diagnosis of infection with herpes simplex virus."}
{"id": "PMID:198492", "title": "Quantitative, semiautomated, enzyme-linked immunosorbent assay for viral antibodies.", "content": "A quantitative, semiautomated, enzyme-linked immunosorbent assay for viral antibodies was developed. The quantitation was based on the comparison of the antibody activity of a serum to a standard curve obtained from a reference serum. This comparison was made automatically by a programmable calculator connected with the spectrophotometer. The assay was simplified further by use of specially designed disposable microcuvettes and micropipettes. The reproducibility of the test was good (1 SD = 5%), and the sensitivity for antibodies to influenza A virus and respiratory syncytial virus was 100-200 times greater than that of complement-fixation or hemagglutination-inhibition techniques. The technique seems especially suitable for virus laboratories in hospitals, where the time required for specific diagnosis of viral diseases can be shortened considerably, not only because of the simple performance of the test, but also because the greater sensitivity allows the shortening of the interval between successive samples of serum down to two or three days.", "contents": "Quantitative, semiautomated, enzyme-linked immunosorbent assay for viral antibodies. A quantitative, semiautomated, enzyme-linked immunosorbent assay for viral antibodies was developed. The quantitation was based on the comparison of the antibody activity of a serum to a standard curve obtained from a reference serum. This comparison was made automatically by a programmable calculator connected with the spectrophotometer. The assay was simplified further by use of specially designed disposable microcuvettes and micropipettes. The reproducibility of the test was good (1 SD = 5%), and the sensitivity for antibodies to influenza A virus and respiratory syncytial virus was 100-200 times greater than that of complement-fixation or hemagglutination-inhibition techniques. The technique seems especially suitable for virus laboratories in hospitals, where the time required for specific diagnosis of viral diseases can be shortened considerably, not only because of the simple performance of the test, but also because the greater sensitivity allows the shortening of the interval between successive samples of serum down to two or three days."}
{"id": "PMID:198493", "title": "Solid-phase enzyme immunoassay for herpes simplex virus.", "content": "An enzyme immunoassay was used for the rapid detection of herpes simplex virus type 1 (HSV-1). The test utilized specific antibodies to HSV-1 attached to a solid phase. A laboratory preparation of HSV-1 was detectable in amounts of greater than or equal to 50 50% tissue culture-infective doses by this method. Tests performed with clinical samples indicated a specificity of 95%. The sensitivity appeared to depend on the length of time the samples were stored. When samples were stored frozen for three to six months, the sensitivity was 46% of that of tissue culture isolations performed when the samples were first collected. The sensitivity was 89% in comparison with attempts at tissue culture reisolation with the same samples at the time of enzyme immunoassay. The immunoassay also detected HSV in seven of 10 positive samples that were stored frozen for no more than two weeks before testing.", "contents": "Solid-phase enzyme immunoassay for herpes simplex virus. An enzyme immunoassay was used for the rapid detection of herpes simplex virus type 1 (HSV-1). The test utilized specific antibodies to HSV-1 attached to a solid phase. A laboratory preparation of HSV-1 was detectable in amounts of greater than or equal to 50 50% tissue culture-infective doses by this method. Tests performed with clinical samples indicated a specificity of 95%. The sensitivity appeared to depend on the length of time the samples were stored. When samples were stored frozen for three to six months, the sensitivity was 46% of that of tissue culture isolations performed when the samples were first collected. The sensitivity was 89% in comparison with attempts at tissue culture reisolation with the same samples at the time of enzyme immunoassay. The immunoassay also detected HSV in seven of 10 positive samples that were stored frozen for no more than two weeks before testing."}
{"id": "PMID:198494", "title": "Detection of soluble antigen of Epstein-Barr virus by the enzyme-linked immunosorbent assay.", "content": "The enzym-linked immunosorbent assay (ELISA) was compared with the microcomplement-fixation test for sensitivity and reliability in detection of antibody to soluble antigen of Epstein-Barr virus. ELISA was found to be more sensitive (up to 160 times more antibody) in detecting levels of antibody than the complement-fixation assay. The ELISA test was shown also to be comparably reliable to the complement-fixation assay in detecting immunity to this antigen; only one false-positive response was found in tests of 21 sera. Because this assay is completely quantifiable, it provides an easy, rapid, and highly sensitive technique for the detection of antibody to antigen of Epstein-Barr virus.", "contents": "Detection of soluble antigen of Epstein-Barr virus by the enzyme-linked immunosorbent assay. The enzym-linked immunosorbent assay (ELISA) was compared with the microcomplement-fixation test for sensitivity and reliability in detection of antibody to soluble antigen of Epstein-Barr virus. ELISA was found to be more sensitive (up to 160 times more antibody) in detecting levels of antibody than the complement-fixation assay. The ELISA test was shown also to be comparably reliable to the complement-fixation assay in detecting immunity to this antigen; only one false-positive response was found in tests of 21 sera. Because this assay is completely quantifiable, it provides an easy, rapid, and highly sensitive technique for the detection of antibody to antigen of Epstein-Barr virus."}
{"id": "PMID:198495", "title": "Magnetic transfer devices for use in solid-phase radioimmunoassays and enzyme-linked immunosorbent assays.", "content": "A method was developed for the simultaneous transfer of large numbers of solid-phase adsorbents in radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). Specially coated ferromagnetic spheres (beads) were used as the solid phase. These beads were transferred from a reaction mixture through a rinse bath to another reaction mixture by magnetic probes. The quality of results obtained with this new methodology compared favorably with that obtained when solid-phase adsorbents were handled individually. The magnetic transfer system provided a high degree of mechanization, thus permitting many more tests to be performed at one time, under almost identical conditions. Certain mechanical features of the test and the micro scale of the reactions provided substantial economy in time and consumption of valuable reagents. The sensitivities of the RIA and ELISA for detection of viral antibody were about the same. An important advantage in using magnetic devices for transfer of beads is that the immune and enzyme-substrate reactions can be started and stopped instantly in either system.", "contents": "Magnetic transfer devices for use in solid-phase radioimmunoassays and enzyme-linked immunosorbent assays. A method was developed for the simultaneous transfer of large numbers of solid-phase adsorbents in radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). Specially coated ferromagnetic spheres (beads) were used as the solid phase. These beads were transferred from a reaction mixture through a rinse bath to another reaction mixture by magnetic probes. The quality of results obtained with this new methodology compared favorably with that obtained when solid-phase adsorbents were handled individually. The magnetic transfer system provided a high degree of mechanization, thus permitting many more tests to be performed at one time, under almost identical conditions. Certain mechanical features of the test and the micro scale of the reactions provided substantial economy in time and consumption of valuable reagents. The sensitivities of the RIA and ELISA for detection of viral antibody were about the same. An important advantage in using magnetic devices for transfer of beads is that the immune and enzyme-substrate reactions can be started and stopped instantly in either system."}
{"id": "PMID:198496", "title": "Comparison of the enzyme-linked immunosorbent assay and the indirect hemagglutination test for detection of antibody to cytomegalovirus.", "content": "Thirty samples of serum were tested for antibody to cytomegalovirus by enzyme-linked immunosorbent assay (ELISA) and indirect hemagglutination (IHA). The two tests were in extremely close agreement. Of the 30 sera evaluated by ELISA, 16 were considered to be positive and 14 were considered negative. In all 16 positive samples, the titers by ELISA were at least twofold to 10-fold higher than the indirect hemagglutination titers. Two of the 14 sera evaluated as negative by the ELISA test had low indirect hemagglutination titers (1:8 and 1:4). They were not detectable at the initial dilution (1:50) of the ELISA test. These two sera might have been classified as positive if the initial dilution in ELISA had been lower than 1:50.", "contents": "Comparison of the enzyme-linked immunosorbent assay and the indirect hemagglutination test for detection of antibody to cytomegalovirus. Thirty samples of serum were tested for antibody to cytomegalovirus by enzyme-linked immunosorbent assay (ELISA) and indirect hemagglutination (IHA). The two tests were in extremely close agreement. Of the 30 sera evaluated by ELISA, 16 were considered to be positive and 14 were considered negative. In all 16 positive samples, the titers by ELISA were at least twofold to 10-fold higher than the indirect hemagglutination titers. Two of the 14 sera evaluated as negative by the ELISA test had low indirect hemagglutination titers (1:8 and 1:4). They were not detectable at the initial dilution (1:50) of the ELISA test. These two sera might have been classified as positive if the initial dilution in ELISA had been lower than 1:50."}
{"id": "PMID:198502", "title": "Uptake of very low density lipoprotein triglyceride by bovine aortic endothelial cells in culture.", "content": "Primary monolayers of calf aortic endothelial cells were presented with isolated human very low density lipoproteins that had been labeled with radioactive triglyceride. The cells were observed to take up triglyceride over a 24 hr period; incorporation increased with exogenous lipoprotein concentrations, and up to 60% of the triglyceride taken up was converted to other cell lipids within 24 hr. When [2-3H]glyceryl tri[1-14C]oleate-labeled very low density lipoprotein was used, the 3H/14C ratio in the cell triglyceride was always similar to that of the exogenous lipoprotein triglyceride. Moreover, no significant hydrolysis of the exogenous very low density lipoprotein triglyceride was observed during the time of exposure to the cells. Similar experiments using doubly-labeled triglyceride exposed to endothelial cells in triglyceride-phospholipid liposome preparations also resulted in incorporation of the exogenous triglyceride without evidence of extracellular hydrolysis. The results indicate that primary monolayers of endothelial cells in culture are able to incorporate and metabolize very low density lipoprotein triglyceride. However, triglyceride does not appear to be significantly hydrolyzed during uptake, suggesting an absence of lipoprotein lipase activity in these cells.", "contents": "Uptake of very low density lipoprotein triglyceride by bovine aortic endothelial cells in culture. Primary monolayers of calf aortic endothelial cells were presented with isolated human very low density lipoproteins that had been labeled with radioactive triglyceride. The cells were observed to take up triglyceride over a 24 hr period; incorporation increased with exogenous lipoprotein concentrations, and up to 60% of the triglyceride taken up was converted to other cell lipids within 24 hr. When [2-3H]glyceryl tri[1-14C]oleate-labeled very low density lipoprotein was used, the 3H/14C ratio in the cell triglyceride was always similar to that of the exogenous lipoprotein triglyceride. Moreover, no significant hydrolysis of the exogenous very low density lipoprotein triglyceride was observed during the time of exposure to the cells. Similar experiments using doubly-labeled triglyceride exposed to endothelial cells in triglyceride-phospholipid liposome preparations also resulted in incorporation of the exogenous triglyceride without evidence of extracellular hydrolysis. The results indicate that primary monolayers of endothelial cells in culture are able to incorporate and metabolize very low density lipoprotein triglyceride. However, triglyceride does not appear to be significantly hydrolyzed during uptake, suggesting an absence of lipoprotein lipase activity in these cells."}
{"id": "PMID:198503", "title": "Common characteristics of the cytochrome P-450 system involved in 18- and 11 beta-hydroxylation of deoxycorticosterone in rat adrenals.", "content": "18- and 11beta-Hydroxylation of deoxycorticosterone and side chain cleavage of cholesterol were studied in mitochondria and submitochondrial reconstituted systems prepared from rat and bovine adrenals. A mass fragmentographic technique was used that allows determination of hydroxylation of both exogenous and endogenous cholesterol. The following results were obtained. (1) Treatment of rats with excess potassium chloride in drinking fluid increased mitochondrial cytochrome P-450 as well as 18- and 11beta-hydroxylase activity in the adrenals. Cholesterol side chain cleavage was not affected. In the presence of excess adrenodoxin and adrenodoxin reductase, cytochrome P-450 isolated from potassium chloride-treated rats had higher 18- and 11beta-hydroxylase activity per nmol than cytochrome P-450 isolated from control rats. The stimulatory effects on 18- and 11beta-hydroxylation were of similar magnitude. (2) Long-term treatment with ACTH increased cholesterol side chain cleavage in the adrenals but had no effect on 18- and 11beta-hydroxylase activity. The amount of cytochrome P-450 in the adrenals was not affected by the treatment. It was shown with isolated mitochondrial cytochrome P-450 in the presence of excess adrenodoxin and adrenodoxin reductase that the effect of ACTH was due to increase of side chain cleavage activity per nmol cytochrome P-450. Side chain cleavage of exogenous cholesterol was affected more than that of endogenous cholesterol. (3) Gel chromatography of soluble cytochrome P-450 prepared from rat and bovine adrenal mitochondria yielded chromatographic fractions having either a high 18- and 11beta-hydroxylase activity and a low cholesterol side chain cleavage activity or the reverse. The ratio between 18- and 11beta-hydroxylase activity was approximately constant, provided the origin of cytochrome P-450 was the same. (4) Addition of progesterone to incubations of deoxycorticosterone with soluble or insoluble rat adrenal cytochrome P-450 competitively inhibited 18- and 11beta-hydroxylation of deoxycorticosterone to the same degree. Addition of deoxycorticosterone competitively inhibited 11beta-hydroxylation of progesterone with the same system. Progesterone was not 18-hydroxylated by the system. From the results obtained, it is concluded that 18- and 11beta-hydroxylation have similar properties and that the binding site for deoxycorticosterone is similar or identical in the two hydroxylations. The possibility that the same specific type of cytochrome P-450 is responsible for both 18- and 11beta-hydroxylation of deoxycorticosterone is discussed.", "contents": "Common characteristics of the cytochrome P-450 system involved in 18- and 11 beta-hydroxylation of deoxycorticosterone in rat adrenals. 18- and 11beta-Hydroxylation of deoxycorticosterone and side chain cleavage of cholesterol were studied in mitochondria and submitochondrial reconstituted systems prepared from rat and bovine adrenals. A mass fragmentographic technique was used that allows determination of hydroxylation of both exogenous and endogenous cholesterol. The following results were obtained. (1) Treatment of rats with excess potassium chloride in drinking fluid increased mitochondrial cytochrome P-450 as well as 18- and 11beta-hydroxylase activity in the adrenals. Cholesterol side chain cleavage was not affected. In the presence of excess adrenodoxin and adrenodoxin reductase, cytochrome P-450 isolated from potassium chloride-treated rats had higher 18- and 11beta-hydroxylase activity per nmol than cytochrome P-450 isolated from control rats. The stimulatory effects on 18- and 11beta-hydroxylation were of similar magnitude. (2) Long-term treatment with ACTH increased cholesterol side chain cleavage in the adrenals but had no effect on 18- and 11beta-hydroxylase activity. The amount of cytochrome P-450 in the adrenals was not affected by the treatment. It was shown with isolated mitochondrial cytochrome P-450 in the presence of excess adrenodoxin and adrenodoxin reductase that the effect of ACTH was due to increase of side chain cleavage activity per nmol cytochrome P-450. Side chain cleavage of exogenous cholesterol was affected more than that of endogenous cholesterol. (3) Gel chromatography of soluble cytochrome P-450 prepared from rat and bovine adrenal mitochondria yielded chromatographic fractions having either a high 18- and 11beta-hydroxylase activity and a low cholesterol side chain cleavage activity or the reverse. The ratio between 18- and 11beta-hydroxylase activity was approximately constant, provided the origin of cytochrome P-450 was the same. (4) Addition of progesterone to incubations of deoxycorticosterone with soluble or insoluble rat adrenal cytochrome P-450 competitively inhibited 18- and 11beta-hydroxylation of deoxycorticosterone to the same degree. Addition of deoxycorticosterone competitively inhibited 11beta-hydroxylation of progesterone with the same system. Progesterone was not 18-hydroxylated by the system. From the results obtained, it is concluded that 18- and 11beta-hydroxylation have similar properties and that the binding site for deoxycorticosterone is similar or identical in the two hydroxylations. The possibility that the same specific type of cytochrome P-450 is responsible for both 18- and 11beta-hydroxylation of deoxycorticosterone is discussed."}
{"id": "PMID:198504", "title": "Characterization of human very low density lipoproteins containing two electrophoretic populations: double pre-beta lipoproteinemia and primary dysbetalipoproteinemia.", "content": "Two discrete populations of very low density lipoproteins, with fast and slow pre-beta electrophoretic mobility, were found in 50% of normolipemic and 30% of hyperlipemic individuals selected at random. The two populations were isolated by preparative electrophoresis from five hyperlipemic subjects. The particles comprising the slow component were smaller than those of the fast component and the slow component contained a larger proportion of cholesteryl esters, free cholesterol, B-apoprotein, and arginine-rich apoprotein and a smaller proportion of triglycerides and the two most anionic apoproteins (R-glutamic acid and R-alanine). The properties of the slow component thus closely resemble those of \"remnant\" very low density lipoproteins that accumulate in blood plasma of functionally hepatectomized rats. The chemical composition of the slow component was also similar to that of the very low density lipoproteins with beta mobility found in primary dysbetalipoproteinemia. However, the proportion of cholesteryl esters and argininerich apoprotein was much higher in the latter. The argininerich apoprotein from very low density lipoproteins of most normolipemic and hyperlipemic subjects separates into three or four major bands upon isoelectric focusing electrophoresis in polyacrylamide gels, with pI varying from 5.57 to 6.03. In very low density lipoproteins from individuals with primary dysbetalipoproteinemia, this protein uniquely contains little or none of the two most cationic bands. The number of bands was constant in all subjects studied. The pattern was the same in very low density lipoproteins with fast and slow pre-beta mobility as well as in the beta and pre-beta components in primary dysbetalipoproteinemia. These results suggest that many individuals have \"remnant\" very low density lipoproteins in their plasma. However, the beta-migrating \"remnant\" that accumulated in large amounts in individuals with primary dysbetalipoproteinemia contains much more arginine-rich protein and this protein is structurally abnormal.", "contents": "Characterization of human very low density lipoproteins containing two electrophoretic populations: double pre-beta lipoproteinemia and primary dysbetalipoproteinemia. Two discrete populations of very low density lipoproteins, with fast and slow pre-beta electrophoretic mobility, were found in 50% of normolipemic and 30% of hyperlipemic individuals selected at random. The two populations were isolated by preparative electrophoresis from five hyperlipemic subjects. The particles comprising the slow component were smaller than those of the fast component and the slow component contained a larger proportion of cholesteryl esters, free cholesterol, B-apoprotein, and arginine-rich apoprotein and a smaller proportion of triglycerides and the two most anionic apoproteins (R-glutamic acid and R-alanine). The properties of the slow component thus closely resemble those of \"remnant\" very low density lipoproteins that accumulate in blood plasma of functionally hepatectomized rats. The chemical composition of the slow component was also similar to that of the very low density lipoproteins with beta mobility found in primary dysbetalipoproteinemia. However, the proportion of cholesteryl esters and argininerich apoprotein was much higher in the latter. The argininerich apoprotein from very low density lipoproteins of most normolipemic and hyperlipemic subjects separates into three or four major bands upon isoelectric focusing electrophoresis in polyacrylamide gels, with pI varying from 5.57 to 6.03. In very low density lipoproteins from individuals with primary dysbetalipoproteinemia, this protein uniquely contains little or none of the two most cationic bands. The number of bands was constant in all subjects studied. The pattern was the same in very low density lipoproteins with fast and slow pre-beta mobility as well as in the beta and pre-beta components in primary dysbetalipoproteinemia. These results suggest that many individuals have \"remnant\" very low density lipoproteins in their plasma. However, the beta-migrating \"remnant\" that accumulated in large amounts in individuals with primary dysbetalipoproteinemia contains much more arginine-rich protein and this protein is structurally abnormal."}
{"id": "PMID:198505", "title": "Apolipoprotein A-II content of human plasma high density lipoproteins measured by radioimmunoassay.", "content": "A double antibody radioimmunoassay for human ApoA-II is reported. ApoA-II isolated from human plasma high density lipoprotein (HDL) by column chromatography migrated as a single band on polyacrylamide disc gel electrophoresis, had the appropriate amino acid composition, and provoked the production of monospecific antisera. (125)I-ApoA-II (iodinated by lactoperoxidase, purified by Sephadex G-75 chromatography) migrated with \"cold\" ApoA-II as a single band on disc gel electrophoresis in SDS. Its specific radioactivity was 5-12 mCi/ micro g. In assays, (0.05 M barbital buffer, 0.01% Triton X-100, pH 8.6) over 90% of (125)I-ApoA-II was bound by excess first antibody and over 95% was displaced by excess \"cold\" ApoA-II. Low density lipoprotein, very low density lipoprotein, ApoA-I, ApoC-II, and ApoC-III displaced no counts. Intraassay and interassay coefficients of variation for lipoprotein or plasma samples were 7 +/- 4 and 11 +/- 6%, respectively. As little as 1.0 ng of ApoA-II was detectable with a precision of 10%. ApoA-II made up 20-25% of the proteins of HDL (d 1.083-1.19), HDL(2) (d 1.083-1.124), and HDL(3) (d 1.124-1.19) on column chromatography. The ApoA-II contents of these HDL fractions were also 20-25% by radioimmunoassay. Similar results were obtained whether assays were carried out on intact or delipidated HDL samples. Thus, in contrast with ApoA-I (only 10% of which is detectable), all of the ApoA-II contents of intact HDL are detected with accuracy by this assay. Plasma levels of ApoA-II in young normolipemic subjects were approximately 40 mg/dl (n = 29). In these subjects, over 98% of ApoA-II was found in the d 1.063-1.21 density fractions.", "contents": "Apolipoprotein A-II content of human plasma high density lipoproteins measured by radioimmunoassay. A double antibody radioimmunoassay for human ApoA-II is reported. ApoA-II isolated from human plasma high density lipoprotein (HDL) by column chromatography migrated as a single band on polyacrylamide disc gel electrophoresis, had the appropriate amino acid composition, and provoked the production of monospecific antisera. (125)I-ApoA-II (iodinated by lactoperoxidase, purified by Sephadex G-75 chromatography) migrated with \"cold\" ApoA-II as a single band on disc gel electrophoresis in SDS. Its specific radioactivity was 5-12 mCi/ micro g. In assays, (0.05 M barbital buffer, 0.01% Triton X-100, pH 8.6) over 90% of (125)I-ApoA-II was bound by excess first antibody and over 95% was displaced by excess \"cold\" ApoA-II. Low density lipoprotein, very low density lipoprotein, ApoA-I, ApoC-II, and ApoC-III displaced no counts. Intraassay and interassay coefficients of variation for lipoprotein or plasma samples were 7 +/- 4 and 11 +/- 6%, respectively. As little as 1.0 ng of ApoA-II was detectable with a precision of 10%. ApoA-II made up 20-25% of the proteins of HDL (d 1.083-1.19), HDL(2) (d 1.083-1.124), and HDL(3) (d 1.124-1.19) on column chromatography. The ApoA-II contents of these HDL fractions were also 20-25% by radioimmunoassay. Similar results were obtained whether assays were carried out on intact or delipidated HDL samples. Thus, in contrast with ApoA-I (only 10% of which is detectable), all of the ApoA-II contents of intact HDL are detected with accuracy by this assay. Plasma levels of ApoA-II in young normolipemic subjects were approximately 40 mg/dl (n = 29). In these subjects, over 98% of ApoA-II was found in the d 1.063-1.21 density fractions."}
{"id": "PMID:198506", "title": "Serum bile acid analysis: a rapid, direct enzymatic method using dual-beam spectrophotofluorimetry.", "content": "The direct quantitative measurement of total bile acids in serum has been achieved using an enzymatic fluorescent method with a dual-beam spectrophotofluorimeter. By use of a 3alpha-hydroxysteroid dehydrogenase, oxidation of bile acids with NAD is completed in 200 seconds with the observed NADH fluorescence being proportional to the concentration of serum bile acids. This method is rapid (8 minutes per individual sample), has an intrinsic sensitivity of +/- micronM of total bile acids, requires no sample preparation and less than 0.8 ml of serum. Paired data analysis using enzymatic fluorescence and gas-liquid chromatographic methods gives a correlation coefficient (r) of 0.99 for 34 samples ranging from 2 to 530 micronM.", "contents": "Serum bile acid analysis: a rapid, direct enzymatic method using dual-beam spectrophotofluorimetry. The direct quantitative measurement of total bile acids in serum has been achieved using an enzymatic fluorescent method with a dual-beam spectrophotofluorimeter. By use of a 3alpha-hydroxysteroid dehydrogenase, oxidation of bile acids with NAD is completed in 200 seconds with the observed NADH fluorescence being proportional to the concentration of serum bile acids. This method is rapid (8 minutes per individual sample), has an intrinsic sensitivity of +/- micronM of total bile acids, requires no sample preparation and less than 0.8 ml of serum. Paired data analysis using enzymatic fluorescence and gas-liquid chromatographic methods gives a correlation coefficient (r) of 0.99 for 34 samples ranging from 2 to 530 micronM."}
{"id": "PMID:198510", "title": "Innervation of the ventral diaphragm of the locust (Locusta migratoria).", "content": "1. Innervation and some electrical properties of the locust ventral diaphragm were investigated with electrophysiological and histological methods. 2. Muscle fibres are coupled electrically. Electrical stimulation evokes a graded active membrane response. 3. Each segment is innervated by four motor neurones as follows. Two motor neurones are situated in each abdominal ganglion. Branches of their axons supply the ventral diaphragm in the respective and the next posterior segment. 4. This pattern of innervation was confirmed by axonal Co and Ni staining of the motor nerve endings. 5. Neuromuscular junctions are excitatory. EPSPs show summation but no facilitation. 6. Spontaneous electrical activity of the diaphragm is to a certain degree coupled to activity of the main inspiratory muscles.", "contents": "Innervation of the ventral diaphragm of the locust (Locusta migratoria). 1. Innervation and some electrical properties of the locust ventral diaphragm were investigated with electrophysiological and histological methods. 2. Muscle fibres are coupled electrically. Electrical stimulation evokes a graded active membrane response. 3. Each segment is innervated by four motor neurones as follows. Two motor neurones are situated in each abdominal ganglion. Branches of their axons supply the ventral diaphragm in the respective and the next posterior segment. 4. This pattern of innervation was confirmed by axonal Co and Ni staining of the motor nerve endings. 5. Neuromuscular junctions are excitatory. EPSPs show summation but no facilitation. 6. Spontaneous electrical activity of the diaphragm is to a certain degree coupled to activity of the main inspiratory muscles."}
{"id": "PMID:198511", "title": "Adult mouse dorsal root ganglia neurons in cell culture.", "content": "A method has been developed for the long-term culture of dissociated adult mouse dorsal root ganglia (DRG). Of critical importance to the success of this technique was a three-hour incubation in collagenase which softened the DRG and permitted gentle dissociation. The morphological and electrophysiological features of the dissociated adult DRG were similar to those observed in previous studies of immature (i.e., embryonic and newborn) DRG in culture and also to those of adult DRG in situ. With regard to electrophysiological work, the adult DRG neurons are superior to embryonic and newborn neurons because of their larger size and greatly increased survival in culture (no degeneration for first six days, and thereafter a relatively slow decrease). The adult neurons regenerated nerve fibers to an extent comparable to that of immature neurons. Therefore, the adult DRG cultures might be useful to study factors influencing regeneration in the adult mammalian nervous system. The adult cultures might also be useful to investigated factors influencing the aging process.", "contents": "Adult mouse dorsal root ganglia neurons in cell culture. A method has been developed for the long-term culture of dissociated adult mouse dorsal root ganglia (DRG). Of critical importance to the success of this technique was a three-hour incubation in collagenase which softened the DRG and permitted gentle dissociation. The morphological and electrophysiological features of the dissociated adult DRG were similar to those observed in previous studies of immature (i.e., embryonic and newborn) DRG in culture and also to those of adult DRG in situ. With regard to electrophysiological work, the adult DRG neurons are superior to embryonic and newborn neurons because of their larger size and greatly increased survival in culture (no degeneration for first six days, and thereafter a relatively slow decrease). The adult neurons regenerated nerve fibers to an extent comparable to that of immature neurons. Therefore, the adult DRG cultures might be useful to study factors influencing regeneration in the adult mammalian nervous system. The adult cultures might also be useful to investigated factors influencing the aging process."}
{"id": "PMID:198513", "title": "Fine structure of cutaneous nerves in ganglioside storage disease.", "content": "Skin punch biopsies of six children suffering from infantile or late onset Tay-Sachs disease, juvenile Sandhoff disease, or GM gangliosidosis type I, contained axons which, when viewed with the electron microscope, were distended by large amorphous black deposits. These are nonspecific residual bodies. Their large numbers indicate severe disturbance of the nerve cell and may be part of the dying back process. The three cases with Tay-Sachs disease had also axonal zebra or complex membranous bodies which appeared to be specific. Cytoplasmic vacuolation of other cells was a feature in the patient with GM1 gangliosidosis. Biopsies of three parents were negative.", "contents": "Fine structure of cutaneous nerves in ganglioside storage disease. Skin punch biopsies of six children suffering from infantile or late onset Tay-Sachs disease, juvenile Sandhoff disease, or GM gangliosidosis type I, contained axons which, when viewed with the electron microscope, were distended by large amorphous black deposits. These are nonspecific residual bodies. Their large numbers indicate severe disturbance of the nerve cell and may be part of the dying back process. The three cases with Tay-Sachs disease had also axonal zebra or complex membranous bodies which appeared to be specific. Cytoplasmic vacuolation of other cells was a feature in the patient with GM1 gangliosidosis. Biopsies of three parents were negative."}
{"id": "PMID:198514", "title": "Mouse spinal cord in cell culture. II. Synaptic activity and circuit behavior.", "content": "1. Neurons in cell cultures of fetal mouse spinal cord (SC) and dorsal root ganglia (DRG) develop extensive synaptic interconnections. 2. No spontaneous synaptic activity was detectable in the presence of tetrodotoxin or an elevated magnsium ion concentration, but statistical analysis of evoked excitatory postsynaptic potentials (EPSPs) indicates that the quantal size was 200-250 muV, which was below the noise level of the recording system used. 3. In a sample of eight RDG-SC and seven SC-SC cell pairs linked by EPSPs, the quantal content of the SC-SC EPSPs was about 3.5-fold larger than for the DRG-SC EPSPs. 4. The extrapolated equilibrium potential for the SC-SC EPSP was about 20 mV positive. The IPSP reversed at a membrane potential of 60-80 mV negative. 5. Some examples of the types of synaptic circuits commonly encountered are given. Only one case of electrical coupling between neurons was found.", "contents": "Mouse spinal cord in cell culture. II. Synaptic activity and circuit behavior. 1. Neurons in cell cultures of fetal mouse spinal cord (SC) and dorsal root ganglia (DRG) develop extensive synaptic interconnections. 2. No spontaneous synaptic activity was detectable in the presence of tetrodotoxin or an elevated magnsium ion concentration, but statistical analysis of evoked excitatory postsynaptic potentials (EPSPs) indicates that the quantal size was 200-250 muV, which was below the noise level of the recording system used. 3. In a sample of eight RDG-SC and seven SC-SC cell pairs linked by EPSPs, the quantal content of the SC-SC EPSPs was about 3.5-fold larger than for the DRG-SC EPSPs. 4. The extrapolated equilibrium potential for the SC-SC EPSP was about 20 mV positive. The IPSP reversed at a membrane potential of 60-80 mV negative. 5. Some examples of the types of synaptic circuits commonly encountered are given. Only one case of electrical coupling between neurons was found."}
{"id": "PMID:198516", "title": "Concentration of 3',5' cyclic adenosine monophosphate in ventricular CSF of patients following severe head trauma.", "content": "Previous studies have demonstrated that cerebrospinal fluid (CSF) from the lateral ventricle of patients without disturbance of sensorium or intracranial pressure, contains 15 to 30 nM 3',5' cyclic adenosine monophosphate (cAMP). The concentration of this cyclic nucleotide was measured by radioimmunoassay in 133 samples of CSF from the lateral ventricle of 26 patients who were comatose following acute head trauma for periods up to 40 days. Concentration of CSF cAMP in diminishing coma Grades V, IV, III, II, and I was 1.5 +/- 0.1 nM; 1.24 +/- 0.34 nM; 3.14 +/- 0.7 NM; 10.06 +/- 3.47 nM; and 13.36 +/-  1.38 nM, respectively. After the sensorium cleared (coma Grade 0), cAMP was 22.0 +/- 1.7 nM. The correlation between the grade of coma and cAMP concentration was -0.80 (p greater than 0.01). These results imply that alteration in the level of consciousness following head trauma is associated with a disturbance of cAMP metabolism within the central nervous system. Possible mechanisms explaining this observation as well as therapeutic implications are discussed.", "contents": "Concentration of 3',5' cyclic adenosine monophosphate in ventricular CSF of patients following severe head trauma. Previous studies have demonstrated that cerebrospinal fluid (CSF) from the lateral ventricle of patients without disturbance of sensorium or intracranial pressure, contains 15 to 30 nM 3',5' cyclic adenosine monophosphate (cAMP). The concentration of this cyclic nucleotide was measured by radioimmunoassay in 133 samples of CSF from the lateral ventricle of 26 patients who were comatose following acute head trauma for periods up to 40 days. Concentration of CSF cAMP in diminishing coma Grades V, IV, III, II, and I was 1.5 +/- 0.1 nM; 1.24 +/- 0.34 nM; 3.14 +/- 0.7 NM; 10.06 +/- 3.47 nM; and 13.36 +/-  1.38 nM, respectively. After the sensorium cleared (coma Grade 0), cAMP was 22.0 +/- 1.7 nM. The correlation between the grade of coma and cAMP concentration was -0.80 (p greater than 0.01). These results imply that alteration in the level of consciousness following head trauma is associated with a disturbance of cAMP metabolism within the central nervous system. Possible mechanisms explaining this observation as well as therapeutic implications are discussed."}
{"id": "PMID:198517", "title": "Cerebrospinal fluid GABA reductions in seizure patients evoked by cerebellar surface stimulation.", "content": "Lumbar cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) levels determined by fluorometric assay in four seizure patients were found to be significantly lower during bilateral, continuous cerebellar stimulation than those determined after a 7-day period without stimulation. The CSF GABA concentrations during chronic unilateral, alternating cerebellar stimulation were reduced in three seizure patients but unchanged in a fourth patient. The percentage decrease in CSF GABA appeared to be independent of cerebellar stimulation frequency. These findings suggest that GABA-mediated neuronal transmission is depressed during cerebellar surface stimulation and this evoked reduction in GABA activity may compromise the efficacy of cerebellar stimulation in the treatment of epilepsy. Lumbar CSF cyclic guanosine monophosphate levels determined by radioimmunoassay were not significantly altered by either mode or frequency of cerebellar stimulation.", "contents": "Cerebrospinal fluid GABA reductions in seizure patients evoked by cerebellar surface stimulation. Lumbar cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) levels determined by fluorometric assay in four seizure patients were found to be significantly lower during bilateral, continuous cerebellar stimulation than those determined after a 7-day period without stimulation. The CSF GABA concentrations during chronic unilateral, alternating cerebellar stimulation were reduced in three seizure patients but unchanged in a fourth patient. The percentage decrease in CSF GABA appeared to be independent of cerebellar stimulation frequency. These findings suggest that GABA-mediated neuronal transmission is depressed during cerebellar surface stimulation and this evoked reduction in GABA activity may compromise the efficacy of cerebellar stimulation in the treatment of epilepsy. Lumbar CSF cyclic guanosine monophosphate levels determined by radioimmunoassay were not significantly altered by either mode or frequency of cerebellar stimulation."}
{"id": "PMID:198518", "title": "Influence of vitamin C restriction on guinea pig adrenal calcium and plasma corticosteroids.", "content": "Some aspects of adrenocortical function were investigated in young male guinea pigs fed an ascorbic acid (AsA)-deficient diet for 7 days, followed by 0.1 mg AsA/100 g body weight/day for 4 days; pair-fed guinea pigs served as controls. Ninety minutes prior to killine, all guinea pigs received either an adrenocorticotropic hormone (ACTH) or saline injection, and 30 minutes prior to killing, all were injected with 20 muCi  45Ca/100 g body weight intraperitoneally. AsA restriction alone caused an 89% reduction in adrenal AsA concentration, but growth rate, adrenal weight and plasma ACTH were not different from those of pair-fed controls. Adrenal radiocalcium uptake, adrenal calcium content and plasma corticosteroids were similar in saline-treated guinea pigs restricted in AsA and the ACTH-treated controls, all of which were significantly higher than the values observed in saline-injected controls. Similar responses of the ACTH-treated controls and the saline-treated mildly deficient guinea pigs indicated that, at the adrenal AsA levels achieved (4.45 to 7.02 mg/100 g tissue), adrenal calcium and plasma corticosteroids increased significantly without the mediation of ACTH.", "contents": "Influence of vitamin C restriction on guinea pig adrenal calcium and plasma corticosteroids. Some aspects of adrenocortical function were investigated in young male guinea pigs fed an ascorbic acid (AsA)-deficient diet for 7 days, followed by 0.1 mg AsA/100 g body weight/day for 4 days; pair-fed guinea pigs served as controls. Ninety minutes prior to killine, all guinea pigs received either an adrenocorticotropic hormone (ACTH) or saline injection, and 30 minutes prior to killing, all were injected with 20 muCi  45Ca/100 g body weight intraperitoneally. AsA restriction alone caused an 89% reduction in adrenal AsA concentration, but growth rate, adrenal weight and plasma ACTH were not different from those of pair-fed controls. Adrenal radiocalcium uptake, adrenal calcium content and plasma corticosteroids were similar in saline-treated guinea pigs restricted in AsA and the ACTH-treated controls, all of which were significantly higher than the values observed in saline-injected controls. Similar responses of the ACTH-treated controls and the saline-treated mildly deficient guinea pigs indicated that, at the adrenal AsA levels achieved (4.45 to 7.02 mg/100 g tissue), adrenal calcium and plasma corticosteroids increased significantly without the mediation of ACTH."}
{"id": "PMID:198520", "title": "Current progress in the treatment of the child with cancer.", "content": "Treatment for the child with cancer has increasingly been on a rational rather than an empiric basis. An understanding has developed of the importance for determining clinical and laboratory features present at diagnosis as an aid not only to establish a prognosis but also to design specific treatment regimens. A system has been developed for bringing new chemotherapeutic agents into clinical trials as effectively as possible. Through both clinical and laboratory studies, an increasing understanding of the biology of cancer is being developed. This understanding will provide the basis for more rational treatment programs in the future. Physicians of different specialty interests have learned to work together to develop coordinated programs of treatment so important to optimal care. By far the most important lesson learned, however, is that cancer in children is not of necessity a fatal disease, even when dissemination has occurred. For the furture, it will be necessary to develop even more effective methods of treatment, and research must provide a better understanding of this disease that may offer the opportunity for prevention, which, after all, is the number one interest of the pediatrician.", "contents": "Current progress in the treatment of the child with cancer. Treatment for the child with cancer has increasingly been on a rational rather than an empiric basis. An understanding has developed of the importance for determining clinical and laboratory features present at diagnosis as an aid not only to establish a prognosis but also to design specific treatment regimens. A system has been developed for bringing new chemotherapeutic agents into clinical trials as effectively as possible. Through both clinical and laboratory studies, an increasing understanding of the biology of cancer is being developed. This understanding will provide the basis for more rational treatment programs in the future. Physicians of different specialty interests have learned to work together to develop coordinated programs of treatment so important to optimal care. By far the most important lesson learned, however, is that cancer in children is not of necessity a fatal disease, even when dissemination has occurred. For the furture, it will be necessary to develop even more effective methods of treatment, and research must provide a better understanding of this disease that may offer the opportunity for prevention, which, after all, is the number one interest of the pediatrician."}
{"id": "PMID:198521", "title": "A viremic phase for herpes zoster in children with cancer.", "content": "Eight childhood cancer patients with herpes zoster were serially tested for the presence of varicella-zoster virus in blood. Cell cultures of leukocyte-rich plasma from four patients were positive for the virus. In this study viremia was clearly related to dissemination of dermal lesions-the spread of zoster lesions outside an infected dermatome. The child with the longest viremic phase, five days, had the longest and most severe course of skin dissemination, as well as biochemical evidence of hepatitis. One patient with viremia had advanced embryonal carcinoma and died of disseminated tumor before her clinical course could be evaluated. These observations, the first to document a viremic phase for herpes zoster in immunosuppressed children, furnish an added criterion for evaluation of antiviral drugs and live-virus vaccines in the treatment and prevention of varicella-zoster infections.", "contents": "A viremic phase for herpes zoster in children with cancer. Eight childhood cancer patients with herpes zoster were serially tested for the presence of varicella-zoster virus in blood. Cell cultures of leukocyte-rich plasma from four patients were positive for the virus. In this study viremia was clearly related to dissemination of dermal lesions-the spread of zoster lesions outside an infected dermatome. The child with the longest viremic phase, five days, had the longest and most severe course of skin dissemination, as well as biochemical evidence of hepatitis. One patient with viremia had advanced embryonal carcinoma and died of disseminated tumor before her clinical course could be evaluated. These observations, the first to document a viremic phase for herpes zoster in immunosuppressed children, furnish an added criterion for evaluation of antiviral drugs and live-virus vaccines in the treatment and prevention of varicella-zoster infections."}
{"id": "PMID:198524", "title": "Is calcium the final mediator of exocytosis in the rat parotid gland?", "content": "Rat parotid slices were partially depleted of cellular Ca by long (80-100 minute) incubations in media containing no added Ca and 5mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). This treatment inhibited the secretory response (release of alpha-amylase) both to isoproterenol and to dibutyryl cyclic adenosine 3':5'-monophosphate. The isoproterenol-stimulated synthesis of cyclic adenosine 3':5'-monophosphate was inhibited by depletion of Ca but not to an extent sufficient to explain the effects of depletion of Ca on secretion. Isoproterenol did not affect influx of 45Ca but stimulated efflux of 45Ca suggesting release of Ca from intracellular stores. Isoproterenol caused vacuolation of the Golgi region and (in high concentration) enhanced the release of 86Rb, responses which are both believed to be mediated by an increase in cytoplasmic Ca concentration. The results of these experiments suggest that isoproterenol acts to increase the tissue level of cyclic adenosine 3':5'-monophosphate which in turn acts to release Ca from intracellular stores. The rise in intracellular Ca concentration is believed to mediate exocytosis.", "contents": "Is calcium the final mediator of exocytosis in the rat parotid gland? Rat parotid slices were partially depleted of cellular Ca by long (80-100 minute) incubations in media containing no added Ca and 5mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). This treatment inhibited the secretory response (release of alpha-amylase) both to isoproterenol and to dibutyryl cyclic adenosine 3':5'-monophosphate. The isoproterenol-stimulated synthesis of cyclic adenosine 3':5'-monophosphate was inhibited by depletion of Ca but not to an extent sufficient to explain the effects of depletion of Ca on secretion. Isoproterenol did not affect influx of 45Ca but stimulated efflux of 45Ca suggesting release of Ca from intracellular stores. Isoproterenol caused vacuolation of the Golgi region and (in high concentration) enhanced the release of 86Rb, responses which are both believed to be mediated by an increase in cytoplasmic Ca concentration. The results of these experiments suggest that isoproterenol acts to increase the tissue level of cyclic adenosine 3':5'-monophosphate which in turn acts to release Ca from intracellular stores. The rise in intracellular Ca concentration is believed to mediate exocytosis."}
{"id": "PMID:198525", "title": "Histamine mediation in muscular vasodilatation induced by beta adrenoceptor stimulation in dogs.", "content": "This study was designed to investigate the possibility of a histamine mediation in muscular vasodilation induced by beta adrenoceptor stimulation. Accordingly, in seven dogs the effects of isoproterenol administration on the release of 14C-histamine from the perfused gracilis muscle were studied. Beta adrenoceptors stimulation induced a vasodilatation, as shown by a decrease in perfusion pressure(-43 +/- 12 mm Hg); simultaneously, a significant increase of the radioactivity measured in the venous blood effluent from the gracilis muscle was observed. Both these events were blocked by propranolol. In the other five dogs, chlorpheniramine was able to reduce the vasodilatation induced by the injection in the gracilis muscle of isoproterenol. Under control conditions, isoproterenol induced a fall in perfusion pressure of 44 +/- 5 mm Hg while, after chlorpheniramine, perfusion pressure decreased by only 24 +/- 4 mm Hg. The results of this study seem to confirm the possibility of a histamine mediation in isoproterenol-induced vasodilatation. However, further investigation is needed in order to identify the exact role of histamine in the geneis of this phenomenon.", "contents": "Histamine mediation in muscular vasodilatation induced by beta adrenoceptor stimulation in dogs. This study was designed to investigate the possibility of a histamine mediation in muscular vasodilation induced by beta adrenoceptor stimulation. Accordingly, in seven dogs the effects of isoproterenol administration on the release of 14C-histamine from the perfused gracilis muscle were studied. Beta adrenoceptors stimulation induced a vasodilatation, as shown by a decrease in perfusion pressure(-43 +/- 12 mm Hg); simultaneously, a significant increase of the radioactivity measured in the venous blood effluent from the gracilis muscle was observed. Both these events were blocked by propranolol. In the other five dogs, chlorpheniramine was able to reduce the vasodilatation induced by the injection in the gracilis muscle of isoproterenol. Under control conditions, isoproterenol induced a fall in perfusion pressure of 44 +/- 5 mm Hg while, after chlorpheniramine, perfusion pressure decreased by only 24 +/- 4 mm Hg. The results of this study seem to confirm the possibility of a histamine mediation in isoproterenol-induced vasodilatation. However, further investigation is needed in order to identify the exact role of histamine in the geneis of this phenomenon."}
{"id": "PMID:198527", "title": "The hepatic microsomal mixed-function oxidase system in man: cofactor effects and the influence of cholestasis.", "content": "Microsomal preparations from 22 surgical specimens of normal, cholestatic or severely diseased human liver were analyzed with respect to the amounts of cytochromes P-450 and b5 and NADPH-cytochrome c reductase present. Normal human liver contained slightly less NADPH-cytochrome c reductase and cytochrome P-450 (mean 102.6 +/- 14.6 nmol/mg of protein per min. and 0.60 +/- 0.10 nmol/mg of protein, respectively) than is found in the adult rat, but wide variations were observed. Cytochrome b5 was present in comparable amounts to that in rat liver, and cytochrome b5/P --450 ratios were slightly increased in human liver as compared with rat liver. Cholestatic liver did not show significant alterations in the specific contents of any of these three components of the microsomal mixed-function oxidase system, but the two livers with severe parenchymal disease showed substantial reductions in all three. In vitro investigations of cofacter interrelationships in the N-demethylation of ethylmorphine by human liver microsomes suggested that NADPH was the favored electron donor, but NADH had a substantial (ca. 20%) synergistic effect (which was not enhanced by cyanide addition). These observations are in keeping with cytochrome b5 having a possible role in cytochrome P-450-mediated drug hydroxylation in man in both the normal state and after onset of cholestasis.", "contents": "The hepatic microsomal mixed-function oxidase system in man: cofactor effects and the influence of cholestasis. Microsomal preparations from 22 surgical specimens of normal, cholestatic or severely diseased human liver were analyzed with respect to the amounts of cytochromes P-450 and b5 and NADPH-cytochrome c reductase present. Normal human liver contained slightly less NADPH-cytochrome c reductase and cytochrome P-450 (mean 102.6 +/- 14.6 nmol/mg of protein per min. and 0.60 +/- 0.10 nmol/mg of protein, respectively) than is found in the adult rat, but wide variations were observed. Cytochrome b5 was present in comparable amounts to that in rat liver, and cytochrome b5/P --450 ratios were slightly increased in human liver as compared with rat liver. Cholestatic liver did not show significant alterations in the specific contents of any of these three components of the microsomal mixed-function oxidase system, but the two livers with severe parenchymal disease showed substantial reductions in all three. In vitro investigations of cofacter interrelationships in the N-demethylation of ethylmorphine by human liver microsomes suggested that NADPH was the favored electron donor, but NADH had a substantial (ca. 20%) synergistic effect (which was not enhanced by cyanide addition). These observations are in keeping with cytochrome b5 having a possible role in cytochrome P-450-mediated drug hydroxylation in man in both the normal state and after onset of cholestasis."}
{"id": "PMID:198528", "title": "The contribution of cholinergic postganglionic neurotransmission to contractions of rabbit detrusor.", "content": "Field stimulation was used to elicit a contractile response in muscle strips from rabbit detrusor. The blockade of this response by tetrodotoxin (1 X 10(-7) M) ranged from 100% at 1 Hz to 86% at 40 Hz. At concentrations which produced strictly muscarinic antagonism (up to 4 X 10(-7) M) atropine depressed the frequency-response curve by about 42% at maximum but was much less effective at frequencies below 10 Hz. Similarly, treatment of the strips with hemicholinium-3 (5.2 X 10(-4) M) for 90 minutes in the presence of field stimulation at 60 Hz, depressed the frequency-response curve by 52% at maximum but produced less depression below 10 Hz. The hemicholinium-3-resistant response was neither depressed further by atropine (4 X 10(-7) M) nor potentiated by physostigmine (2 X 10(-6) M). Although hemicholinium-3 has antimuscarinic and anticholinesterase properties, these were found not to interfere with the tests for residual cholinergic transmission. Therefore, it was concluded that only part of the motor neurotransmission in rabbit detrusor is cholinergic. The remaining portion is predominant at frequencies below 10 Hz and is postulated to involve a chemical mediator other than acetylcholine.", "contents": "The contribution of cholinergic postganglionic neurotransmission to contractions of rabbit detrusor. Field stimulation was used to elicit a contractile response in muscle strips from rabbit detrusor. The blockade of this response by tetrodotoxin (1 X 10(-7) M) ranged from 100% at 1 Hz to 86% at 40 Hz. At concentrations which produced strictly muscarinic antagonism (up to 4 X 10(-7) M) atropine depressed the frequency-response curve by about 42% at maximum but was much less effective at frequencies below 10 Hz. Similarly, treatment of the strips with hemicholinium-3 (5.2 X 10(-4) M) for 90 minutes in the presence of field stimulation at 60 Hz, depressed the frequency-response curve by 52% at maximum but produced less depression below 10 Hz. The hemicholinium-3-resistant response was neither depressed further by atropine (4 X 10(-7) M) nor potentiated by physostigmine (2 X 10(-6) M). Although hemicholinium-3 has antimuscarinic and anticholinesterase properties, these were found not to interfere with the tests for residual cholinergic transmission. Therefore, it was concluded that only part of the motor neurotransmission in rabbit detrusor is cholinergic. The remaining portion is predominant at frequencies below 10 Hz and is postulated to involve a chemical mediator other than acetylcholine."}
{"id": "PMID:198530", "title": "The effect of catecholamines on Na-K transport and membrane potential in rat soleus muscle.", "content": "1. The action of catecholamines on the transport and the distribution of Na and K and the resting membrane potential (E(M)) has been investigated in soleus muscles isolated from fed rats.2. In a substrate-free Krebs-Ringer bicarbonate buffer adrenaline (ADR) (6 x 10(-6)M) increased (22)Na efflux by 83%, (42)K influx by 34%, and E(M) by 10%. Similar effects were exerted by noradrenaline (NA), phenylephrine, salbutamol and isoprenaline. The effects of ADR on Na-K transport and E(M) were suppressed by ouabain (10(-3)M) and propranolol (10(-5)M), but not by thymoxamine (10(-5)M) or tetracaine (10(-4)M).3. Following 90 min of incubation in the presence of ADR (6 x 10(-6)M), the intracellular K/Na-ratio was increased threefold. NA produced almost the same change, and both catecholamines seem to induce a new steady-state distribution of Na and K which can be maintained for several hours in vitro.4. The effect of ADR on (22)Na efflux and E(M) could be detected at concentrations down to 6 x 10(-9) and 6 x 10(-10)M, respectively, and half-maximum increase was obtained at around 2 x 10(-8)M. NA was at least one order of magnitude less potent.5. The effect of low concentrations of ADR on (22)Na efflux was potentiated by theophylline (2 mM). When added together, dibutyryl-cyclic AMP and theophylline mimicked the action of ADR on (22)Na efflux, (42)K influx, Na/K content and E(M). Ouabain (10(-3)M) also suppressed the effect of dibutyryl-cyclic AMP and theophylline on Na-K transport.6. Following the addition of ouabain (10(-3)M), E(M) rapidly dropped from a mean of -71 to -63 mV, and then showed a slow linear fall for up to 4hr.7. The hyperpolarization induced by ADR was associated with a decrease in membrane conductance, (22)Na influx and (42)K efflux. The time course and the response to ouabain suggests that all of these effects are secondary to stimulation of the active coupled transport of Na and K.8. It is concluded that in rat soleus muscle, the active Na-K transport is electrogenic and susceptible to stimulation by catecholamines via beta-adrenoceptors. This effect is mediated by adenyl cyclase activation and may account for the increase in E(M) and the intracellular K/Na ratio.", "contents": "The effect of catecholamines on Na-K transport and membrane potential in rat soleus muscle. 1. The action of catecholamines on the transport and the distribution of Na and K and the resting membrane potential (E(M)) has been investigated in soleus muscles isolated from fed rats.2. In a substrate-free Krebs-Ringer bicarbonate buffer adrenaline (ADR) (6 x 10(-6)M) increased (22)Na efflux by 83%, (42)K influx by 34%, and E(M) by 10%. Similar effects were exerted by noradrenaline (NA), phenylephrine, salbutamol and isoprenaline. The effects of ADR on Na-K transport and E(M) were suppressed by ouabain (10(-3)M) and propranolol (10(-5)M), but not by thymoxamine (10(-5)M) or tetracaine (10(-4)M).3. Following 90 min of incubation in the presence of ADR (6 x 10(-6)M), the intracellular K/Na-ratio was increased threefold. NA produced almost the same change, and both catecholamines seem to induce a new steady-state distribution of Na and K which can be maintained for several hours in vitro.4. The effect of ADR on (22)Na efflux and E(M) could be detected at concentrations down to 6 x 10(-9) and 6 x 10(-10)M, respectively, and half-maximum increase was obtained at around 2 x 10(-8)M. NA was at least one order of magnitude less potent.5. The effect of low concentrations of ADR on (22)Na efflux was potentiated by theophylline (2 mM). When added together, dibutyryl-cyclic AMP and theophylline mimicked the action of ADR on (22)Na efflux, (42)K influx, Na/K content and E(M). Ouabain (10(-3)M) also suppressed the effect of dibutyryl-cyclic AMP and theophylline on Na-K transport.6. Following the addition of ouabain (10(-3)M), E(M) rapidly dropped from a mean of -71 to -63 mV, and then showed a slow linear fall for up to 4hr.7. The hyperpolarization induced by ADR was associated with a decrease in membrane conductance, (22)Na influx and (42)K efflux. The time course and the response to ouabain suggests that all of these effects are secondary to stimulation of the active coupled transport of Na and K.8. It is concluded that in rat soleus muscle, the active Na-K transport is electrogenic and susceptible to stimulation by catecholamines via beta-adrenoceptors. This effect is mediated by adenyl cyclase activation and may account for the increase in E(M) and the intracellular K/Na ratio."}
{"id": "PMID:198531", "title": "Regulation of amylase release from dispersed pancreatic acinar cells.", "content": "1. A study has been made of factors influencing release of amylase from dispersed pancreatic acinar cells. 2. In the basal, unstimulated, condition cells released 2-3% of the total amylase present in 30 min. 3. The rate of amylase release was stimulated 50-70% by C-terminal octapeptide of cholecystokinin (CCK-OP, maximally effective concentration, 3 X 10(-10) M); carbamylcholine (maximally effective concentration, 10(-5 M); secretin (maximally effective concentration greater than 10(-6) M); vasoactive intestinal peptide (VIP, maximally effective concentration, 10(-8) M); and adenosine 3':5' monophosphate (cyclic AMP) and guanosine 3':5' monophosphate (cyclic GMP) as well as their dibutyryl derivatives (maximally effective concentrations, 10(-3) M). 4. The responses to CCK-OP or carbamylcholine were potentiated by secretin, VIP or dibutyryl cyclic AMP. 5. The responses to secretin or VIP were potentiated by CCK-OP, carbamylcholine, or dibutyryl cyclic GMP. 6. There appear to be two pathways for the regulation of amylase release from pancreatic acinar cells: one pathway can be stimulated by cholecystokinin or cholinergic agonists, and the response to these stimuli is mediated by cyclic GMP; the other pathway can be stimulated by secretin or VIP, and the response to these stimuli is mediated by cyclic AMP.", "contents": "Regulation of amylase release from dispersed pancreatic acinar cells. 1. A study has been made of factors influencing release of amylase from dispersed pancreatic acinar cells. 2. In the basal, unstimulated, condition cells released 2-3% of the total amylase present in 30 min. 3. The rate of amylase release was stimulated 50-70% by C-terminal octapeptide of cholecystokinin (CCK-OP, maximally effective concentration, 3 X 10(-10) M); carbamylcholine (maximally effective concentration, 10(-5 M); secretin (maximally effective concentration greater than 10(-6) M); vasoactive intestinal peptide (VIP, maximally effective concentration, 10(-8) M); and adenosine 3':5' monophosphate (cyclic AMP) and guanosine 3':5' monophosphate (cyclic GMP) as well as their dibutyryl derivatives (maximally effective concentrations, 10(-3) M). 4. The responses to CCK-OP or carbamylcholine were potentiated by secretin, VIP or dibutyryl cyclic AMP. 5. The responses to secretin or VIP were potentiated by CCK-OP, carbamylcholine, or dibutyryl cyclic GMP. 6. There appear to be two pathways for the regulation of amylase release from pancreatic acinar cells: one pathway can be stimulated by cholecystokinin or cholinergic agonists, and the response to these stimuli is mediated by cyclic GMP; the other pathway can be stimulated by secretin or VIP, and the response to these stimuli is mediated by cyclic AMP."}
{"id": "PMID:198532", "title": "Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise.", "content": "1. Five subjects trained for 8 weeks on a bicycle ergometer for an average of 40 min/day, four times a week at a work load requiring 80% of the maximal oxygen uptake (V(O2 max.)). V(O2 max.) determinations were performed, and muscle biopsies from the quadriceps femoris muscle (vastus lateralis) were taken before, as well as repeatedly during, the training period. The muscle biopsies were histochemically stained for fibre-types (myofibrillar ATPase) and capillaries (amylase-PAS method), and analysed biochemically for succinate dehydrogenase and cytochrome oxidase activities.2. The training programme resulted in a 16% increase in V(O2 max.), a 20% increase in capillary density, a 20% increase in mean fibre area, and an approximately 40% increase in the activities of succinate dehydrogenase and cytochrome oxidase.3. The capillary supply to type I, IIA and IIB fibres, expressed as the mean number of capillaries in contact with each fibre-type, relative to fibre-type area, increased equally.4. The present study shows that endurance training constitutes a powerful stimulus for capillary proliferation in human skeletal muscle.", "contents": "Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise. 1. Five subjects trained for 8 weeks on a bicycle ergometer for an average of 40 min/day, four times a week at a work load requiring 80% of the maximal oxygen uptake (V(O2 max.)). V(O2 max.) determinations were performed, and muscle biopsies from the quadriceps femoris muscle (vastus lateralis) were taken before, as well as repeatedly during, the training period. The muscle biopsies were histochemically stained for fibre-types (myofibrillar ATPase) and capillaries (amylase-PAS method), and analysed biochemically for succinate dehydrogenase and cytochrome oxidase activities.2. The training programme resulted in a 16% increase in V(O2 max.), a 20% increase in capillary density, a 20% increase in mean fibre area, and an approximately 40% increase in the activities of succinate dehydrogenase and cytochrome oxidase.3. The capillary supply to type I, IIA and IIB fibres, expressed as the mean number of capillaries in contact with each fibre-type, relative to fibre-type area, increased equally.4. The present study shows that endurance training constitutes a powerful stimulus for capillary proliferation in human skeletal muscle."}
{"id": "PMID:198533", "title": "A study of excitatory neuromuscular transmission in the bovine trachea.", "content": "1. The excitatory innervation of bovine tracheal smooth muscle has been studied with the sucrose-gap apparatus.2. Single 2 ms electrical stimuli applied to the whole tissue excited intrinsic nerves, and produced a small transient depolarization of the smooth muscle, the excitatory junction potential (e.j.p.). The e.j.p. caused a twitch-type contraction; twitches and e.j.p.s summated during repetitive stimulation but facilitation was not observed, and action potentials were never elicited.3. The effects of electrical stimulation could be abolished by atropine (5 x 10(-7) mol/l) and augmented by neostigmine (4 x 10(-6) mol/l), and were mimicked by exogenous acetylcholine (1.0 mug/ml).4. With the electron microscope, the density of innervation was found to be low (one axon per ninety smooth muscle cells). Axons were found in small groups in the clefts between bundles of cells, but no axons penetrated within the muscle bundles. Naked axon varicosities containing agranular vesicles were seen, but no axon approached within 200 nm of a smooth muscle cell.5. It is difficult to reconcile the sparsity of innervation with the dependence of the tissue on nerve excitation to initiate activity.", "contents": "A study of excitatory neuromuscular transmission in the bovine trachea. 1. The excitatory innervation of bovine tracheal smooth muscle has been studied with the sucrose-gap apparatus.2. Single 2 ms electrical stimuli applied to the whole tissue excited intrinsic nerves, and produced a small transient depolarization of the smooth muscle, the excitatory junction potential (e.j.p.). The e.j.p. caused a twitch-type contraction; twitches and e.j.p.s summated during repetitive stimulation but facilitation was not observed, and action potentials were never elicited.3. The effects of electrical stimulation could be abolished by atropine (5 x 10(-7) mol/l) and augmented by neostigmine (4 x 10(-6) mol/l), and were mimicked by exogenous acetylcholine (1.0 mug/ml).4. With the electron microscope, the density of innervation was found to be low (one axon per ninety smooth muscle cells). Axons were found in small groups in the clefts between bundles of cells, but no axons penetrated within the muscle bundles. Naked axon varicosities containing agranular vesicles were seen, but no axon approached within 200 nm of a smooth muscle cell.5. It is difficult to reconcile the sparsity of innervation with the dependence of the tissue on nerve excitation to initiate activity."}
{"id": "PMID:198534", "title": "An analysis of the actions of prostaglandin E1 on membrane currents and contraction in uterine smooth muscle.", "content": "1. The effects of prostaglandin E(1) have been studied on the transmembrane potentials, ionic currents, and contractions in isolated myometrial strips from pregnant rats by means of a double sucrose gap apparatus.2. At low concentrations (10(-8) g/ml.), prostaglandin E(1) reduced the duration (though not the amplitude) of the action potential, but significantly increased the contraction. The inward current was unchanged, as well as the phasic component of the contraction. However, the tonic contraction, recorded when the transmembrane calcium influx was blocked selectively with D 600, was stimulated significantly, and the outward current secondarily increased.3. At maximally effective doses (10(-6) g/ml.), the electrical response to prostaglandin E(1) consisted of a slight depolarization, while a large contracture developed. The depolarization and contracture were unaffected by the removal of external calcium. The inward current was reduced by prostaglandin E(1) and the reversal potential was shifted towards less positive values of voltage, indicating a decrease in the driving force and consequently, an increase in the internal calcium concentration.4. Dibutyryl-c-AMP (5 x 10(-4)M) produced a marked relaxation of the resting tension and a slight hyperpolarization of the uterine membrane. Under these conditions, a triggered action potential was able to evoke a larger contractile response. However, prostaglandin E(1) is known to increase tissue c-AMP, so that its contractile effect cannot be mediated by c-AMP.5. It is suggested that prostaglandin E(1) acts essentially by increasing the intracellular calcium concentration. This might result from the translocation of membrane-bound calcium from surface microvesicles or sarcoplasmic reticulum. The increase in internal calcium concentration could, in turn, lead to an increase in the outward current intensity.", "contents": "An analysis of the actions of prostaglandin E1 on membrane currents and contraction in uterine smooth muscle. 1. The effects of prostaglandin E(1) have been studied on the transmembrane potentials, ionic currents, and contractions in isolated myometrial strips from pregnant rats by means of a double sucrose gap apparatus.2. At low concentrations (10(-8) g/ml.), prostaglandin E(1) reduced the duration (though not the amplitude) of the action potential, but significantly increased the contraction. The inward current was unchanged, as well as the phasic component of the contraction. However, the tonic contraction, recorded when the transmembrane calcium influx was blocked selectively with D 600, was stimulated significantly, and the outward current secondarily increased.3. At maximally effective doses (10(-6) g/ml.), the electrical response to prostaglandin E(1) consisted of a slight depolarization, while a large contracture developed. The depolarization and contracture were unaffected by the removal of external calcium. The inward current was reduced by prostaglandin E(1) and the reversal potential was shifted towards less positive values of voltage, indicating a decrease in the driving force and consequently, an increase in the internal calcium concentration.4. Dibutyryl-c-AMP (5 x 10(-4)M) produced a marked relaxation of the resting tension and a slight hyperpolarization of the uterine membrane. Under these conditions, a triggered action potential was able to evoke a larger contractile response. However, prostaglandin E(1) is known to increase tissue c-AMP, so that its contractile effect cannot be mediated by c-AMP.5. It is suggested that prostaglandin E(1) acts essentially by increasing the intracellular calcium concentration. This might result from the translocation of membrane-bound calcium from surface microvesicles or sarcoplasmic reticulum. The increase in internal calcium concentration could, in turn, lead to an increase in the outward current intensity."}
{"id": "PMID:198543", "title": "Improving patient care through measurement: goal importance and achievement scaling.", "content": "Sophisticated treatment record keeping requires something more than a focus on problems. An emphasis on positive aspects of treatment, i.e., on goals may be more appropriate for certain patients or for certain types of treatment or at specific stages of an illness. Unfortunately, currently available methods of quantifying goal importance and achievement are not entirely satisfactory for general everday use. GIA is proposed as a simple procedure for quantifying judgments of the importance of a treatment goal, of the extent to which that goal is achieved and of determining the social value of what treatment has accomplished. GIA ratings have considerable potential for improving patient care through measurement.", "contents": "Improving patient care through measurement: goal importance and achievement scaling. Sophisticated treatment record keeping requires something more than a focus on problems. An emphasis on positive aspects of treatment, i.e., on goals may be more appropriate for certain patients or for certain types of treatment or at specific stages of an illness. Unfortunately, currently available methods of quantifying goal importance and achievement are not entirely satisfactory for general everday use. GIA is proposed as a simple procedure for quantifying judgments of the importance of a treatment goal, of the extent to which that goal is achieved and of determining the social value of what treatment has accomplished. GIA ratings have considerable potential for improving patient care through measurement."}
{"id": "PMID:198544", "title": "3-N-Substituted aminomethyl derivatives of rifamycin SV. A convenient method of synthesis, cyclization of certain derivatives, and anticellular and antiviral activities of several derivatives.", "content": "A new synthesis of Mannich bases of rifamycin SV using the Borch2 procedure with rifaldehyde is described. This new synthesis offers two advantages over the previously published method. It provides a route to monoalkyl-aminomethylrifamycins (le-h) and to unsubstituted aminomethylrifamycins that were not accessible by the old procedure. The new method also offers a preparative route to Mannich bases 1a and 1b were needed in multigram quantities for biological testing. In addition, the cyclization of certain of the monoalkylaminomethylrifamycins to the novel N,15-didehydro-15-epi[methano(alkylimino)]rifamycin SV derivatives (2) is described. The anticellular and antiviral effects of representatives of both series of compounds against cultured mouse cells and murine oncornavirus are are discussed.", "contents": "3-N-Substituted aminomethyl derivatives of rifamycin SV. A convenient method of synthesis, cyclization of certain derivatives, and anticellular and antiviral activities of several derivatives. A new synthesis of Mannich bases of rifamycin SV using the Borch2 procedure with rifaldehyde is described. This new synthesis offers two advantages over the previously published method. It provides a route to monoalkyl-aminomethylrifamycins (le-h) and to unsubstituted aminomethylrifamycins that were not accessible by the old procedure. The new method also offers a preparative route to Mannich bases 1a and 1b were needed in multigram quantities for biological testing. In addition, the cyclization of certain of the monoalkylaminomethylrifamycins to the novel N,15-didehydro-15-epi[methano(alkylimino)]rifamycin SV derivatives (2) is described. The anticellular and antiviral effects of representatives of both series of compounds against cultured mouse cells and murine oncornavirus are are discussed."}
{"id": "PMID:198545", "title": "Prostaglandin isosteres. 1. (8-Aza-,  8,10-diaza-, and 8-aza-11-thia)-9-oxoprostanoic acids and their derivatives.", "content": "A series of novel (8-aza-, 8,10-diaza-, and 8-aza-11-thia)-9-oxoprostanoic acids has been synthesized and evaluated for their ability to mimic the E series prostaglandins in stimulating cAMP formation in the mouse ovary and in binding to the rat kidney plasma prostaglandin receptor. 7-[2-(3-Hydroxyoctyl)-1,1,4-trioxo-3-thiazolidinyl]heptanoic acid markedly stimulates cAMP formation at reasonable pharmacological concentrations and avidly binds to the rat kidney prostaglandin receptor.", "contents": "Prostaglandin isosteres. 1. (8-Aza-,  8,10-diaza-, and 8-aza-11-thia)-9-oxoprostanoic acids and their derivatives. A series of novel (8-aza-, 8,10-diaza-, and 8-aza-11-thia)-9-oxoprostanoic acids has been synthesized and evaluated for their ability to mimic the E series prostaglandins in stimulating cAMP formation in the mouse ovary and in binding to the rat kidney plasma prostaglandin receptor. 7-[2-(3-Hydroxyoctyl)-1,1,4-trioxo-3-thiazolidinyl]heptanoic acid markedly stimulates cAMP formation at reasonable pharmacological concentrations and avidly binds to the rat kidney prostaglandin receptor."}
{"id": "PMID:198546", "title": "11,12-secoprostaglandins. 4. 7-(N-alkylmethanesulfonamido) heptanoic acids.", "content": "A series of 7-(N-alkylmethanesulfonamido) heptanoic acids has been prepared which represents an extension of our 8-aza-11,12-secoprostaglandin studies. The studies. The compounds mimic the natural prostaglandins in that they markedly stimulate cAMP formation in the mouse ovary assay.", "contents": "11,12-secoprostaglandins. 4. 7-(N-alkylmethanesulfonamido) heptanoic acids. A series of 7-(N-alkylmethanesulfonamido) heptanoic acids has been prepared which represents an extension of our 8-aza-11,12-secoprostaglandin studies. The studies. The compounds mimic the natural prostaglandins in that they markedly stimulate cAMP formation in the mouse ovary assay."}
{"id": "PMID:198547", "title": "Synthesis of spin-labeled nitroxyl esters of steroids.", "content": "The preparations of spin-labeled nitroxyl esters of prednisone, cortisone, deoxycorticosterone, and cholesterol are described. The ESR spectra indicate that the esters of the three steroids with an oxygen atom at the 11 position have narrower band widths than those with only protons at that position. Mass spectral, chemical, and ESR studies confirmed the structures and purity of the compounds prepared. Reaction of four esters with prednisone antibodies showed reversible binding and large crossover binding.", "contents": "Synthesis of spin-labeled nitroxyl esters of steroids. The preparations of spin-labeled nitroxyl esters of prednisone, cortisone, deoxycorticosterone, and cholesterol are described. The ESR spectra indicate that the esters of the three steroids with an oxygen atom at the 11 position have narrower band widths than those with only protons at that position. Mass spectral, chemical, and ESR studies confirmed the structures and purity of the compounds prepared. Reaction of four esters with prednisone antibodies showed reversible binding and large crossover binding."}
{"id": "PMID:198555", "title": "Cell proliferation and histologic classification of bronchogenic carcinoma.", "content": "The rate of cell proliferation of 99 bronchogenic carcinomas (94 primary tumors and 5 metastases) was evaluated from the labeling index after in vitro incorporation of [3H]thymidine; the rate was then correlated with the histologic tumor type according to the classification of the World Health Organization (WHO). Cell proliferation was significantly slower in adenocarcinoma (WHO type III) than in squamous cell carcinoma (WHO type I), small cell anaplastic carcinoma (WHO type II), and large cell carcinoma (WHO type IV). Cells proliferated at a significantly higher rate in large cell carcinoma than in the squamous cell type, whereas no significant difference was observed between the other cell types. Dedifferentiated forms of squamous cell carcinomas had a higher rate of cell proliferation than did differentiated forms of the same cell type. Metastases of small cell anaplastic carcinoma did not differ in cell proliferation from primary tumors of the same cell type.", "contents": "Cell proliferation and histologic classification of bronchogenic carcinoma. The rate of cell proliferation of 99 bronchogenic carcinomas (94 primary tumors and 5 metastases) was evaluated from the labeling index after in vitro incorporation of [3H]thymidine; the rate was then correlated with the histologic tumor type according to the classification of the World Health Organization (WHO). Cell proliferation was significantly slower in adenocarcinoma (WHO type III) than in squamous cell carcinoma (WHO type I), small cell anaplastic carcinoma (WHO type II), and large cell carcinoma (WHO type IV). Cells proliferated at a significantly higher rate in large cell carcinoma than in the squamous cell type, whereas no significant difference was observed between the other cell types. Dedifferentiated forms of squamous cell carcinomas had a higher rate of cell proliferation than did differentiated forms of the same cell type. Metastases of small cell anaplastic carcinoma did not differ in cell proliferation from primary tumors of the same cell type."}
{"id": "PMID:198556", "title": "B-lymphocytes and T-lymphocytes in three types of bovine lymphosarcoma.", "content": "Lymphoid cells of peripheral blood, lymph nodes, and thymus from clinically normal cattle, cattle infected with bovine leukemia virus (BLV), and cattle with lymphosarcoma were characterized for T- and B-cell surface markers. B-cells were detected by the erythrocyte-antibody-complement (EAC) rosette test and the surface immunoglobulin (sig) immunofluorescence assay. Peripheral blood from BLV-infected cattle had a higher than normal percentage of B-cells by both EAC rosette and sig immunofluorescence assays. Lymphoid cells from tumorous lymph nodes of cattle with the adult type of lymphosarcoma had a higher than normal percentage of sig-bearing cells, but in the same cell preparation the EAC rosette-positive cells were fewer than sig-positive cells. T-cells were detected by the erythrocyte rosette test. The percentage of T-cells by this test in lymph nodes of adult type lymphosarcoma was lower than that in normal cattle. A distinctly lower than normal percentage of lymphocytes could be characterized as either B- or T-cells in lymph nodes thymus, and peripheral blood from the calf type and thymic type of lymphosarcoma.", "contents": "B-lymphocytes and T-lymphocytes in three types of bovine lymphosarcoma. Lymphoid cells of peripheral blood, lymph nodes, and thymus from clinically normal cattle, cattle infected with bovine leukemia virus (BLV), and cattle with lymphosarcoma were characterized for T- and B-cell surface markers. B-cells were detected by the erythrocyte-antibody-complement (EAC) rosette test and the surface immunoglobulin (sig) immunofluorescence assay. Peripheral blood from BLV-infected cattle had a higher than normal percentage of B-cells by both EAC rosette and sig immunofluorescence assays. Lymphoid cells from tumorous lymph nodes of cattle with the adult type of lymphosarcoma had a higher than normal percentage of sig-bearing cells, but in the same cell preparation the EAC rosette-positive cells were fewer than sig-positive cells. T-cells were detected by the erythrocyte rosette test. The percentage of T-cells by this test in lymph nodes of adult type lymphosarcoma was lower than that in normal cattle. A distinctly lower than normal percentage of lymphocytes could be characterized as either B- or T-cells in lymph nodes thymus, and peripheral blood from the calf type and thymic type of lymphosarcoma."}
{"id": "PMID:198557", "title": "Pathology of human-mouse somatic cell hybrid tumors.", "content": "Somatic cell hybrids between mouse peritoneal macrophages and simian virus 40-transformed human cells injected sc into nude mice resulted in a formation of tumors with two distinct growth rates and growth patterns: 1) rapid growing, irregularly circumscribed, with necrotic foci and prominent vascular channels lined by tumor cells and 2) slow growing, small, well-circumscribed, and nonvascular. Individual tumor cells were ultrastructurally classified as undifferentiated mesenchymal cells indistinguishable within these two tumor types. Characteristics of each tumor type were retained during subsequent passages in nude mice.", "contents": "Pathology of human-mouse somatic cell hybrid tumors. Somatic cell hybrids between mouse peritoneal macrophages and simian virus 40-transformed human cells injected sc into nude mice resulted in a formation of tumors with two distinct growth rates and growth patterns: 1) rapid growing, irregularly circumscribed, with necrotic foci and prominent vascular channels lined by tumor cells and 2) slow growing, small, well-circumscribed, and nonvascular. Individual tumor cells were ultrastructurally classified as undifferentiated mesenchymal cells indistinguishable within these two tumor types. Characteristics of each tumor type were retained during subsequent passages in nude mice."}
{"id": "PMID:198558", "title": "Detection of bovine leukemia virus in B-lymphocytes by the syncytia induction assay.", "content": "Bovine peripheral blood lymphocytes (PBL's) from 3 cows and 1 steer infected with bovine leukemia virus (BLV) were separated by fractionation through nylon wool columns into nylon-adherent and nonadherent cell populations. Nylon-adherent cells were enriched in B-lymphocytes, as determined by the presence of surface membrane immunoglobulins (slg), whereas nylon-nonadherent cells or \"non-B-lymphocytes\" contained few slg-bearing cells. PBL's and separated B- and non-B-lymphocyte populations were assayed for the presence of BLV by the induction of syncytia in bovine embryonic spleen cells. PBL's and B-lymphocyte populations both produced many syncytia, whereas non-B-lymphocytes yielded few or no syncytia. The specificity of syncytia formation by anti-BLV serum. PBL's from 2 control animals were negative for syncytia induction. This study presents further evidence that B-lymphocytes are the target cells for BLV infection.", "contents": "Detection of bovine leukemia virus in B-lymphocytes by the syncytia induction assay. Bovine peripheral blood lymphocytes (PBL's) from 3 cows and 1 steer infected with bovine leukemia virus (BLV) were separated by fractionation through nylon wool columns into nylon-adherent and nonadherent cell populations. Nylon-adherent cells were enriched in B-lymphocytes, as determined by the presence of surface membrane immunoglobulins (slg), whereas nylon-nonadherent cells or \"non-B-lymphocytes\" contained few slg-bearing cells. PBL's and separated B- and non-B-lymphocyte populations were assayed for the presence of BLV by the induction of syncytia in bovine embryonic spleen cells. PBL's and B-lymphocyte populations both produced many syncytia, whereas non-B-lymphocytes yielded few or no syncytia. The specificity of syncytia formation by anti-BLV serum. PBL's from 2 control animals were negative for syncytia induction. This study presents further evidence that B-lymphocytes are the target cells for BLV infection."}
{"id": "PMID:198559", "title": "Subcellular distribution of the tumor-specific transplantation antigen of simian virus 40-transformed cells.", "content": "TU-5, a simian virus 40 (SV40)-transformed cell line of BALB/c origin, expressed the SV40-specific T-antigen and a transplantation  antigen (TSTA). Nuclei and plasma membranes were prepared from these cells and shown on the basis of the distribution of T-antigen and histocompatibility (H-2) antigens to be relatively free of cross contamination. Most of the TSTA, estimated by tumor rejection, was associated with the nuclear fraction.", "contents": "Subcellular distribution of the tumor-specific transplantation antigen of simian virus 40-transformed cells. TU-5, a simian virus 40 (SV40)-transformed cell line of BALB/c origin, expressed the SV40-specific T-antigen and a transplantation  antigen (TSTA). Nuclei and plasma membranes were prepared from these cells and shown on the basis of the distribution of T-antigen and histocompatibility (H-2) antigens to be relatively free of cross contamination. Most of the TSTA, estimated by tumor rejection, was associated with the nuclear fraction."}
{"id": "PMID:198560", "title": "Biologic and biochemical properties of detergent-solubilized tumor-specific transplantation antigen from a simian virus 40-induced neoplasm: brief communication.", "content": "The detergent Nonidet P40 was used to solubilize tumor-specific transplantation antigens (TSTA) from crude membranes obtained from dissociated cells of simian virus 40-induced sarcoma of BALB/c mice. A good recovery of specific tumor rejection activity was observed. One fraction, fraction V, was obtained following polyacrylamide-agarose filtration of the solubilized material, and this fraction contained most of the activity. An increased specific activity followed gel filtration. Preliminary data from lectin column chromatography of the active fraction V indicated a separation of TSTA activity from H-2 activity.", "contents": "Biologic and biochemical properties of detergent-solubilized tumor-specific transplantation antigen from a simian virus 40-induced neoplasm: brief communication. The detergent Nonidet P40 was used to solubilize tumor-specific transplantation antigens (TSTA) from crude membranes obtained from dissociated cells of simian virus 40-induced sarcoma of BALB/c mice. A good recovery of specific tumor rejection activity was observed. One fraction, fraction V, was obtained following polyacrylamide-agarose filtration of the solubilized material, and this fraction contained most of the activity. An increased specific activity followed gel filtration. Preliminary data from lectin column chromatography of the active fraction V indicated a separation of TSTA activity from H-2 activity."}
{"id": "PMID:198561", "title": "Some factors affecting the expression of Epstein-Barr virus-associated membrane antigens.", "content": "The effect of two factors, L-arginine concentration and phytohemagglutinin (PHA) stimulation, on the expression of Epstein-Barr virus (EBV)-associated membrane antigens (MA) was evaluated. An EBV-producer cell line, AV-1, was cultivated in Eagle's basal medium with Earle's salts, supplemented with various L-arginine concentrations ranging from 0.0 to 20.0 mM. In most of the L-arginine concentrations, the number of cells expressing MA decreased within the first 24 hours. This decrease was followed by a marked increase in MA-positive cells at 48 hours and a slight decrease between 48 and 72 hours. Statistical evaluation, however, revealed no significant differences in the level of MA expression among cells exposed to the various L-arginine concentrations. These findings were discussed in relation to the cell cycle dependence of L-arginine-deficient media as a virus-activating agent. AV-1 cell cultures were treated with PHA and observed at 24-hour intervals for 72 hours. Within the first 24 hours, the percentage of cells showing MA was markedly increased. This was followed by a rapid decline in percentage of MA-positive cells within the next 24 hours. Treatment of an EBV-nonproducer cell line, NC37, with PHA resulted in the production of MA in approximately 11% of the cells within the first 24 hours. The number of MA-positive cells gradually declined over the next 48 hours. No viral capsid antigens were detected in these cells. The data suggested either complete or partial activation of the latent EBV genome by PHA.", "contents": "Some factors affecting the expression of Epstein-Barr virus-associated membrane antigens. The effect of two factors, L-arginine concentration and phytohemagglutinin (PHA) stimulation, on the expression of Epstein-Barr virus (EBV)-associated membrane antigens (MA) was evaluated. An EBV-producer cell line, AV-1, was cultivated in Eagle's basal medium with Earle's salts, supplemented with various L-arginine concentrations ranging from 0.0 to 20.0 mM. In most of the L-arginine concentrations, the number of cells expressing MA decreased within the first 24 hours. This decrease was followed by a marked increase in MA-positive cells at 48 hours and a slight decrease between 48 and 72 hours. Statistical evaluation, however, revealed no significant differences in the level of MA expression among cells exposed to the various L-arginine concentrations. These findings were discussed in relation to the cell cycle dependence of L-arginine-deficient media as a virus-activating agent. AV-1 cell cultures were treated with PHA and observed at 24-hour intervals for 72 hours. Within the first 24 hours, the percentage of cells showing MA was markedly increased. This was followed by a rapid decline in percentage of MA-positive cells within the next 24 hours. Treatment of an EBV-nonproducer cell line, NC37, with PHA resulted in the production of MA in approximately 11% of the cells within the first 24 hours. The number of MA-positive cells gradually declined over the next 48 hours. No viral capsid antigens were detected in these cells. The data suggested either complete or partial activation of the latent EBV genome by PHA."}
{"id": "PMID:198562", "title": "Epstein-Barr virus and nasopharyngeal carcinoma: is there an etiologic relationship?", "content": "Antibody titers to all the Epstein-Barr virus (EBV)-related antigens were significant elevated (P less than 0.001) in patients with nasopharyngeal carcinoma (NPC) compared with those of controls. EBV, early antigen, and anti-diffuse titers of Chinese-American and black patients with NPC were higher than those of white patients with NPC. Epstein-Barr viral capsid antigen antibody titers were elevated in white patients with squamous cell carcinoma of the pharynx, regardless of subsite. These results raise doubts about the specificity of the association between EBV and NPC.", "contents": "Epstein-Barr virus and nasopharyngeal carcinoma: is there an etiologic relationship? Antibody titers to all the Epstein-Barr virus (EBV)-related antigens were significant elevated (P less than 0.001) in patients with nasopharyngeal carcinoma (NPC) compared with those of controls. EBV, early antigen, and anti-diffuse titers of Chinese-American and black patients with NPC were higher than those of white patients with NPC. Epstein-Barr viral capsid antigen antibody titers were elevated in white patients with squamous cell carcinoma of the pharynx, regardless of subsite. These results raise doubts about the specificity of the association between EBV and NPC."}
{"id": "PMID:198564", "title": "Experimental carcinoma of liver in macaque monkeys exposed to diethylnitrosamine and hepatitis B virus.", "content": "The effects of treatments with diethylnitrosamine (DENA) and hepatitis B virus (HBV) on macaque monkeys were investigated by virus serology and by light and electron microscopy. The experimental groups comprised 43 newborn or juvenile cynomolgus and rhesus monkeys of both sexes. HBV neither had a carcinogenic effect nor increased the oncogenic effect of DENA. However, HBV given to juvenile primates before treatment with DENA resulted in subsequent gross and microscopic alterations consistent with mild hepatitis and postnecrotic cirrhosis; multifocal liver carcinoma apparently developed within these cirrhotic nodules. The pathologic findings in the experimental animals were strikingly similar to those observed in liver cancer patients.", "contents": "Experimental carcinoma of liver in macaque monkeys exposed to diethylnitrosamine and hepatitis B virus. The effects of treatments with diethylnitrosamine (DENA) and hepatitis B virus (HBV) on macaque monkeys were investigated by virus serology and by light and electron microscopy. The experimental groups comprised 43 newborn or juvenile cynomolgus and rhesus monkeys of both sexes. HBV neither had a carcinogenic effect nor increased the oncogenic effect of DENA. However, HBV given to juvenile primates before treatment with DENA resulted in subsequent gross and microscopic alterations consistent with mild hepatitis and postnecrotic cirrhosis; multifocal liver carcinoma apparently developed within these cirrhotic nodules. The pathologic findings in the experimental animals were strikingly similar to those observed in liver cancer patients."}
{"id": "PMID:198565", "title": "Susceptibility of common marmosets (Callithrix jacchus) to oncogenic and attenuated strains of Herpesvirus saimiri.", "content": "Adult common marmosets, inoculated with either of 2 oncogenic Herpesvirus saimiri (HVS) strains, developed fatal lymphoproliferative disease within 23-25 days post inoculation (PI). The disease was identical to HVS-induced lymphoma in cotton-topped and white-lipped marmosets. Common marmosets inoculated with an attenuated HVS strain developed persistent infection; virus has been recovered from cocultivated lymphocytes of these animals for more than 384 days PI.", "contents": "Susceptibility of common marmosets (Callithrix jacchus) to oncogenic and attenuated strains of Herpesvirus saimiri. Adult common marmosets, inoculated with either of 2 oncogenic Herpesvirus saimiri (HVS) strains, developed fatal lymphoproliferative disease within 23-25 days post inoculation (PI). The disease was identical to HVS-induced lymphoma in cotton-topped and white-lipped marmosets. Common marmosets inoculated with an attenuated HVS strain developed persistent infection; virus has been recovered from cocultivated lymphocytes of these animals for more than 384 days PI."}
{"id": "PMID:198566", "title": "Elution of tumor-directed antibody from kidneys of mammary tumor-bearing mice.", "content": "Immunoglobulin-containing eluates, prepared from kidneys of Paris RIII mammary tumor-bearing mice approximately 10 months old, were incubated with frozen sections of mouse mammary tumor and normal lactating mammary gland and examined by immunofluorescence. The eluates diffusely strained the tumor but did not stain the nonneoplastic lactating mammary gland. Mammary tumor and normal lactating mammary gland were both stained by an antiserum to mammary tumor virus (MuMTV). The euglobulin portion of the eluates, when fractionated on a Sephadex G-200 column, yielded an IgG fraction which was shown by immunodiffusion to react with Paris RIII mammary tumor extract and with anti-mouse globulin but not with nonneoplastic mouse tissue extracts. Since the lactating mammary glands of these animals contain MuMTV, the antibody-containing fraction eluted from the kidneys appeared to be tumor directed rather than virus directed.", "contents": "Elution of tumor-directed antibody from kidneys of mammary tumor-bearing mice. Immunoglobulin-containing eluates, prepared from kidneys of Paris RIII mammary tumor-bearing mice approximately 10 months old, were incubated with frozen sections of mouse mammary tumor and normal lactating mammary gland and examined by immunofluorescence. The eluates diffusely strained the tumor but did not stain the nonneoplastic lactating mammary gland. Mammary tumor and normal lactating mammary gland were both stained by an antiserum to mammary tumor virus (MuMTV). The euglobulin portion of the eluates, when fractionated on a Sephadex G-200 column, yielded an IgG fraction which was shown by immunodiffusion to react with Paris RIII mammary tumor extract and with anti-mouse globulin but not with nonneoplastic mouse tissue extracts. Since the lactating mammary glands of these animals contain MuMTV, the antibody-containing fraction eluted from the kidneys appeared to be tumor directed rather than virus directed."}
{"id": "PMID:198567", "title": "Transformation of rat liver epithelial cells by Kirsten murine sarcoma virus.", "content": "We studied the transformation of epithelial, diploid cell lines (RL-33 and RL-34) derived from W rat liver by the Kirsten murine sarcoma virus. On days 4-5 after virus infection, the epithelial cells began to pile up focally, forming small projections and releasing round cells from the foci. The epithelial cells grew in  chains or as islets and grew in suspension above the cells attached to the bottom of the flasks when the cultures reached the confluent stage. The virus titration pattern was \"one-hit.\" Three classes of transformed cells were isolated with respect to virus release and antigen expression: 1) virus producer, 2) non-producer, and 3) sarcoma-positive, leukemia-negative cells. When transplanted sc into newborn rats, the transformed cells produced sarcomas. The transformed cells formed within 1-3 days larger aggregates than those of their normal counterpart cells when suspended in liquid growth medium above an agar base. Aggregate  properties (size, viability, and proliferation) of transformed cells correlated with growth in soft agar and tumorigenicity. RNA-dependent DNA polymerase and type C virus particles were readily induced in the normal rat liver epithelial cells after exposure to 5-iodo-2'-deoxyuridine.", "contents": "Transformation of rat liver epithelial cells by Kirsten murine sarcoma virus. We studied the transformation of epithelial, diploid cell lines (RL-33 and RL-34) derived from W rat liver by the Kirsten murine sarcoma virus. On days 4-5 after virus infection, the epithelial cells began to pile up focally, forming small projections and releasing round cells from the foci. The epithelial cells grew in  chains or as islets and grew in suspension above the cells attached to the bottom of the flasks when the cultures reached the confluent stage. The virus titration pattern was \"one-hit.\" Three classes of transformed cells were isolated with respect to virus release and antigen expression: 1) virus producer, 2) non-producer, and 3) sarcoma-positive, leukemia-negative cells. When transplanted sc into newborn rats, the transformed cells produced sarcomas. The transformed cells formed within 1-3 days larger aggregates than those of their normal counterpart cells when suspended in liquid growth medium above an agar base. Aggregate  properties (size, viability, and proliferation) of transformed cells correlated with growth in soft agar and tumorigenicity. RNA-dependent DNA polymerase and type C virus particles were readily induced in the normal rat liver epithelial cells after exposure to 5-iodo-2'-deoxyuridine."}
{"id": "PMID:198568", "title": "Induction of simian virus 40 (SV40) transplantation immunity in mice by SV40-transformed cells of various species.", "content": "Specific tumor rejection was obtained with the use of simian virus 40 (SV40)-transformed cells from several species including man, rat, ape, sheep, and hamster. Growth of the syngeneic sarcoma mKSA in BALB/c mice was strikingly inhibited following a single immunization with as few as 10(3) intact, viable cells. Non-SV40-transformed cells did not induce tumor rejection activity nor did SV40-transformed lines induce immunity against  the 3-methylcholanthrene-induced sarcoma Meth A, syngeneic with BALB/c mice. A close relationship existed between the tumor rejection antigen, the tumor-specific transplantation antigen (TSTA) located on the plasma membrane, and the intranuclear tumor antigen (T-ag). Both were associated with the DNA sequence of the early region of the SV40 genome, and TSTA activity was found in the nucleus. However, we did not observe a close parallelism between T-ag activity and TSTA. Neverthesless, the results strongly suggested that TSTA, like T-ag, was encoded by the virus.", "contents": "Induction of simian virus 40 (SV40) transplantation immunity in mice by SV40-transformed cells of various species. Specific tumor rejection was obtained with the use of simian virus 40 (SV40)-transformed cells from several species including man, rat, ape, sheep, and hamster. Growth of the syngeneic sarcoma mKSA in BALB/c mice was strikingly inhibited following a single immunization with as few as 10(3) intact, viable cells. Non-SV40-transformed cells did not induce tumor rejection activity nor did SV40-transformed lines induce immunity against  the 3-methylcholanthrene-induced sarcoma Meth A, syngeneic with BALB/c mice. A close relationship existed between the tumor rejection antigen, the tumor-specific transplantation antigen (TSTA) located on the plasma membrane, and the intranuclear tumor antigen (T-ag). Both were associated with the DNA sequence of the early region of the SV40 genome, and TSTA activity was found in the nucleus. However, we did not observe a close parallelism between T-ag activity and TSTA. Neverthesless, the results strongly suggested that TSTA, like T-ag, was encoded by the virus."}
{"id": "PMID:198569", "title": "Inhibitory effect of a polychlorinated biphenyl (Aroclor 1254) on aflatoxin B1 carcinogenesis in rainbow trout (Salmo gairdneri).", "content": "Duplicate lots of 120 rainbow trout (Salmo gairdneri) fingerlings were fed for 1 year semipurified diets containing 6 ppb aflatoxin B1 (AFB1), 100 ppm Aroclor 1254 (a polychlorinated biphenyl), and 6 ppb AFB1 plus 100 ppm Aroclor 1254. Appropriate controls were also maintained. Samples were taken at 1, 2, 4, 6, 9, and 12 months to monitor tumor incidence, Aroclor 1254 accumulation, and histopathology of liver, spleen, and kidney tissues. At the end of the year, 26 of 37 (70.3%) trout fed 6 ppb AFB1 had hepatocellular carcinomas, compared to 14 of 46 (30.4%) trout fed 6 ppb AFB1 plus 100 ppm Aroclor 1254, a highly significant reduction in tumor incidence in the trout on the Aroclor 1254-containing diet. None of the control or Aroclor 1254-fed fish had liver tumors. Levels of Aroclor 1254 increased rapidly during the first 6 months, then plateaued at approximately 80 ppm on a whole-fish basis. AFB1 inhibited growth but Aroclor 1254 did not. Glycogen depletion of hepatocytes and hyperemia, and white pulp depletion of the spleen were the only changes induced by Aroclor 1254.", "contents": "Inhibitory effect of a polychlorinated biphenyl (Aroclor 1254) on aflatoxin B1 carcinogenesis in rainbow trout (Salmo gairdneri). Duplicate lots of 120 rainbow trout (Salmo gairdneri) fingerlings were fed for 1 year semipurified diets containing 6 ppb aflatoxin B1 (AFB1), 100 ppm Aroclor 1254 (a polychlorinated biphenyl), and 6 ppb AFB1 plus 100 ppm Aroclor 1254. Appropriate controls were also maintained. Samples were taken at 1, 2, 4, 6, 9, and 12 months to monitor tumor incidence, Aroclor 1254 accumulation, and histopathology of liver, spleen, and kidney tissues. At the end of the year, 26 of 37 (70.3%) trout fed 6 ppb AFB1 had hepatocellular carcinomas, compared to 14 of 46 (30.4%) trout fed 6 ppb AFB1 plus 100 ppm Aroclor 1254, a highly significant reduction in tumor incidence in the trout on the Aroclor 1254-containing diet. None of the control or Aroclor 1254-fed fish had liver tumors. Levels of Aroclor 1254 increased rapidly during the first 6 months, then plateaued at approximately 80 ppm on a whole-fish basis. AFB1 inhibited growth but Aroclor 1254 did not. Glycogen depletion of hepatocytes and hyperemia, and white pulp depletion of the spleen were the only changes induced by Aroclor 1254."}
{"id": "PMID:198570", "title": "Transmission of mammary tumor virus in mouse strain DD: further support for the uniqueness of strain GR.", "content": "Outcrosses between high tumor mouse strain DD and low-incidence strains BALB/c and C57BL to produce reciprocal F1 susceptible offspring of both types resulted in high incidences of mammary tumors in (DD female X BALB/c male)F1 and (DD female X C57BL male)F1 females but not in the reciprocal hybrids with DD as the male parent. The finding that transmission of murine mammary tumor virus (MuMTV) in DD was through the milk, as most often observed in mouse strains, further supported the uniqueness of strain GR in which MuMTV is transmitted by either parent.", "contents": "Transmission of mammary tumor virus in mouse strain DD: further support for the uniqueness of strain GR. Outcrosses between high tumor mouse strain DD and low-incidence strains BALB/c and C57BL to produce reciprocal F1 susceptible offspring of both types resulted in high incidences of mammary tumors in (DD female X BALB/c male)F1 and (DD female X C57BL male)F1 females but not in the reciprocal hybrids with DD as the male parent. The finding that transmission of murine mammary tumor virus (MuMTV) in DD was through the milk, as most often observed in mouse strains, further supported the uniqueness of strain GR in which MuMTV is transmitted by either parent."}
{"id": "PMID:198571", "title": "High incidence of ependymomas induced by BK virus, a human papovavirus: brief communication.", "content": "Ependymomas were produced in 44 of 50 Syrian golden hamsters and in 9 of 31 outbred Swiss mice inoculated intracerebrally with high-titer, purified BK virus (BKV). Tumors contained a T-antigen that reacted with BKV-specific T-antibody in immunofluorescence and complement-fixation tests. A proportion of tumor-bearing animals had antibodies to BKV T-antigen in their sera. BKV could be rescued from two tumor cell lines by Sendal virus-mediated fusion with Vero cells. A low, or lack of, oncogenic activity was displayed by BKV inoculated sc, ip, or iv.", "contents": "High incidence of ependymomas induced by BK virus, a human papovavirus: brief communication. Ependymomas were produced in 44 of 50 Syrian golden hamsters and in 9 of 31 outbred Swiss mice inoculated intracerebrally with high-titer, purified BK virus (BKV). Tumors contained a T-antigen that reacted with BKV-specific T-antibody in immunofluorescence and complement-fixation tests. A proportion of tumor-bearing animals had antibodies to BKV T-antigen in their sera. BKV could be rescued from two tumor cell lines by Sendal virus-mediated fusion with Vero cells. A low, or lack of, oncogenic activity was displayed by BKV inoculated sc, ip, or iv."}
{"id": "PMID:198572", "title": "Characterization of a new type of human papillomavirus that causes skin warts.", "content": "A human papillomavirus (HPV) was isolated from the lesions of a patient (ML) bearing numerous hand common warts. This virus was compared with the well-characterized HPV found in typical plantar warts (plantar HPV). ML and plantar HPV DNAs have similar molecular weights (5.26 x 10(6) and 5.23 x 10(6), respectively) but were shown to be different by restriction enzyme analysis. When the cleavage products of both DNAs by endonuclease EcoRI, BamI, HpaI, or Hind were analyzed by electron microscopy, one, two, one, and four fragments were detected for ML HPV DNA instead of the two, one, two, and six fragments, respectively, detected for plantar HPV DNA. In contrast to plantar HPV DNA, a high proportion of ML HPV DNA molecules were resistant to these restriction enzymes. Most, if not all, of the molecules were either resistant to BamI and sensitive to EcoRI or sensitive to BamI and resistant to EcoRI. After denaturation and renaturation of the cleavage products of ML HPV DNA by a mixture of the two enzymes, the circular \"heteroduplexes\" formed showed one to three heterology loops corresponding to about 4 to 8% of the genome length. No sequence homology was detected between ML and plantar HPV DNAs by cRNA-DNA filter hybridization, by measuring the reassociation kinetics of an iodinated plantar HPV DNA in the presence of a 25-fold excess of ML HPV DNA, or by the heteroduplex technique. The two viruses had distinct electrophoretic polypeptide patterns and showed no antigenic cross-reaction by immunodiffusion or immunofluorescence techniques. Preliminary cRNA-DNA hybridization experiments, using viral DNAs from single or pooled plantar or hand warts, suggest that hand common warts are associated with viruses similar or related to ML HPV. The existence of at least two distinct types of HPVs that cause skin warts was demonstrated; they were provisionally called HPV type 1 and HPV type 2, with plantar HPV and ML HPV as prototypical viruses, respectively.", "contents": "Characterization of a new type of human papillomavirus that causes skin warts. A human papillomavirus (HPV) was isolated from the lesions of a patient (ML) bearing numerous hand common warts. This virus was compared with the well-characterized HPV found in typical plantar warts (plantar HPV). ML and plantar HPV DNAs have similar molecular weights (5.26 x 10(6) and 5.23 x 10(6), respectively) but were shown to be different by restriction enzyme analysis. When the cleavage products of both DNAs by endonuclease EcoRI, BamI, HpaI, or Hind were analyzed by electron microscopy, one, two, one, and four fragments were detected for ML HPV DNA instead of the two, one, two, and six fragments, respectively, detected for plantar HPV DNA. In contrast to plantar HPV DNA, a high proportion of ML HPV DNA molecules were resistant to these restriction enzymes. Most, if not all, of the molecules were either resistant to BamI and sensitive to EcoRI or sensitive to BamI and resistant to EcoRI. After denaturation and renaturation of the cleavage products of ML HPV DNA by a mixture of the two enzymes, the circular \"heteroduplexes\" formed showed one to three heterology loops corresponding to about 4 to 8% of the genome length. No sequence homology was detected between ML and plantar HPV DNAs by cRNA-DNA filter hybridization, by measuring the reassociation kinetics of an iodinated plantar HPV DNA in the presence of a 25-fold excess of ML HPV DNA, or by the heteroduplex technique. The two viruses had distinct electrophoretic polypeptide patterns and showed no antigenic cross-reaction by immunodiffusion or immunofluorescence techniques. Preliminary cRNA-DNA hybridization experiments, using viral DNAs from single or pooled plantar or hand warts, suggest that hand common warts are associated with viruses similar or related to ML HPV. The existence of at least two distinct types of HPVs that cause skin warts was demonstrated; they were provisionally called HPV type 1 and HPV type 2, with plantar HPV and ML HPV as prototypical viruses, respectively."}
{"id": "PMID:198573", "title": "State of the viral DNA in rat cells transformed by polyma virus. II. Identification of the cells containing nonintegrated viral DNA and the effect of viral mutations.", "content": "F2408 rat cells transformed by polyoma virus contained integrated and nonintegrated viral DNA. The presence of nonintegrated viral DNA is under control of the A early viral function. Polyoma ts-a-transformed rat cells lose the free viral DNA when growth at the nonpermissive temperature (40 degrees C), but they reexpress it 1 to 3 days after they are shifted back to the permissive temperature. In contrast, rat cells transformed by a late viral mutant, ts-8, contain free viral DNA at both permissive and nonpermissive temperatures. Treatment of the transformed rat cells with mitomycin C produces a large increase in the quantity of free viral DNA and some production of infectious virus. Experiments of in situ hybridization, with 3H-labeled polyoma complementary RNA as a probe, show that only a minority (approximately 0.1%) of the transformed cells contain nonintegrated viral DNA at any given time. These results suggest that the presence of free viral DNA in polyoma-transformed rat cells is caused by a spontaneous induction of viral DNA replication, occurring with low but constant probability in the transformed cell population, and that the free viral DNA molecules originate from the integrated ones, probably through a phenomenon of excision and limited replication.", "contents": "State of the viral DNA in rat cells transformed by polyma virus. II. Identification of the cells containing nonintegrated viral DNA and the effect of viral mutations. F2408 rat cells transformed by polyoma virus contained integrated and nonintegrated viral DNA. The presence of nonintegrated viral DNA is under control of the A early viral function. Polyoma ts-a-transformed rat cells lose the free viral DNA when growth at the nonpermissive temperature (40 degrees C), but they reexpress it 1 to 3 days after they are shifted back to the permissive temperature. In contrast, rat cells transformed by a late viral mutant, ts-8, contain free viral DNA at both permissive and nonpermissive temperatures. Treatment of the transformed rat cells with mitomycin C produces a large increase in the quantity of free viral DNA and some production of infectious virus. Experiments of in situ hybridization, with 3H-labeled polyoma complementary RNA as a probe, show that only a minority (approximately 0.1%) of the transformed cells contain nonintegrated viral DNA at any given time. These results suggest that the presence of free viral DNA in polyoma-transformed rat cells is caused by a spontaneous induction of viral DNA replication, occurring with low but constant probability in the transformed cell population, and that the free viral DNA molecules originate from the integrated ones, probably through a phenomenon of excision and limited replication."}
{"id": "PMID:198574", "title": "Evidence for simian virus 40 (SV40) coding of SV40 T-antigen and the SV40-specific proteins in HeLa cells infected with nondefective adenovirus type 2-SV40 hybrid viruses.", "content": "HeLa cells infected with the nondefective adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrid viruses (Ad2(+)ND1, Ad2(+)ND2, Ad2(+)ND4, and Ad2(+)ND5) synthesize SV40-specific proteins ranging in size from 28,000 to 100,000 daltons. By analysis of their methionine-containing tryptic peptides, we demonstrated that all these proteins shared common amino acid sequences. Most methionine-containing tryptic peptides derived from proteins of smaller size were contained within the proteins of larger size. Seventeen of the 21 methionine-containing tryptic peptides of the largest SV40-specific protein (100,000 daltons) from Ad2(+)ND4-infected cells were identical to methionine-containing peptides of SV40 T-antigen immunoprecipitated from extracts of SV40-infected cells. All of the methionine-containing tryptic peptides of the Ad2(+)ND4 100,000-dalton protein were found in SV40 T-antigen immunoprecipitated from SV40-transformed cells. All SV40-specific proteins observed in vivo could be synthesized in vitro using the wheat germ cell-free system and SV40-specific RNA from hybrid virus-infected cells that was purified by hybridization to SV40 DNA. As proof of identity, the in vitro products were shown to have methionine-containing tryptic peptides identical to those of their in vivo counterparts. Based on the extensive overlap in amino acid sequence between the SV40-specific proteins from hybrid virus-infected cells and SV40 T-antigen from SV40-infected and -transformed cells, we conclude that at least the major portion of the SV40-specific proteins cannot be Ad2 coded. From the in vitro synthesis experiments with SV40-selected RNA, we further conclude that the SV40-specific proteins must be SV40 coded and not host coded. Since SV40 T-antigen is related to the SV40-specific proteins, it must also be SV40 coded.", "contents": "Evidence for simian virus 40 (SV40) coding of SV40 T-antigen and the SV40-specific proteins in HeLa cells infected with nondefective adenovirus type 2-SV40 hybrid viruses. HeLa cells infected with the nondefective adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrid viruses (Ad2(+)ND1, Ad2(+)ND2, Ad2(+)ND4, and Ad2(+)ND5) synthesize SV40-specific proteins ranging in size from 28,000 to 100,000 daltons. By analysis of their methionine-containing tryptic peptides, we demonstrated that all these proteins shared common amino acid sequences. Most methionine-containing tryptic peptides derived from proteins of smaller size were contained within the proteins of larger size. Seventeen of the 21 methionine-containing tryptic peptides of the largest SV40-specific protein (100,000 daltons) from Ad2(+)ND4-infected cells were identical to methionine-containing peptides of SV40 T-antigen immunoprecipitated from extracts of SV40-infected cells. All of the methionine-containing tryptic peptides of the Ad2(+)ND4 100,000-dalton protein were found in SV40 T-antigen immunoprecipitated from SV40-transformed cells. All SV40-specific proteins observed in vivo could be synthesized in vitro using the wheat germ cell-free system and SV40-specific RNA from hybrid virus-infected cells that was purified by hybridization to SV40 DNA. As proof of identity, the in vitro products were shown to have methionine-containing tryptic peptides identical to those of their in vivo counterparts. Based on the extensive overlap in amino acid sequence between the SV40-specific proteins from hybrid virus-infected cells and SV40 T-antigen from SV40-infected and -transformed cells, we conclude that at least the major portion of the SV40-specific proteins cannot be Ad2 coded. From the in vitro synthesis experiments with SV40-selected RNA, we further conclude that the SV40-specific proteins must be SV40 coded and not host coded. Since SV40 T-antigen is related to the SV40-specific proteins, it must also be SV40 coded."}
{"id": "PMID:198575", "title": "Characterization of the autoregulation of simian virus 40 gene A.", "content": "Cells infected by tsA mutants of simian virus 40 (SV40) overproduce early RNA. Overproduction results from failure of the temperature-sensitive A protein (T antigen) to inhibit early transcription. The amount of early RNA in the cytoplasm, determined quantitatively from the kinetics of hybridization to labeled complementary SV40 DNA, was elevated at both permissive (32 degrees C) and nonpermissive (41 degrees C) temperatures in all the early mutants tested (tsA7, -30, -58, and -209), but not in the late mutant tsB4. The amount of early RNA in a culture maintained at 32 degrees C for 72 h and then shifted to 41 degrees C was maximum when each cell was infected initially with at least one plaque-forming unit of tsA58. Azidocytidine (2'-deoxy-2'-azidocytidine), which inhibits initiation of DNA synthesis, did not cause overproduction of early RNA in cells infected with wild-type SV40, showing that the effect seen with tsA mutants is not due to interference with initiation of DNA synthesis per se. In parallel infections at 41 degrees C, the amount of early RNA per copy of viral DNA was as much as 2,000 times greater with tsA58 than with wild-type SV40, even though there was no replication of the tsA58 DNA. Synthesis of late RNA could not be detected during the first 20 h of an infection by either virus at 32 degrees C, indicating that late and early transcription are under different control. In three cell lines transformed by tsA mutants, the amount of early RNA increased moderately after a shift from 32 to 41 degrees C, whereas with homologous cells transformed by wild-type virus, the amount of early RNA decreased, indicating that the A protein may be able to repress transcription of integrated SV40 DNA. All the observations are consistent with a simple model in which the binding of A protein at the origin of replication blocks either binding of RNA polymerase to the early promoter or its progress through the early gene(s).", "contents": "Characterization of the autoregulation of simian virus 40 gene A. Cells infected by tsA mutants of simian virus 40 (SV40) overproduce early RNA. Overproduction results from failure of the temperature-sensitive A protein (T antigen) to inhibit early transcription. The amount of early RNA in the cytoplasm, determined quantitatively from the kinetics of hybridization to labeled complementary SV40 DNA, was elevated at both permissive (32 degrees C) and nonpermissive (41 degrees C) temperatures in all the early mutants tested (tsA7, -30, -58, and -209), but not in the late mutant tsB4. The amount of early RNA in a culture maintained at 32 degrees C for 72 h and then shifted to 41 degrees C was maximum when each cell was infected initially with at least one plaque-forming unit of tsA58. Azidocytidine (2'-deoxy-2'-azidocytidine), which inhibits initiation of DNA synthesis, did not cause overproduction of early RNA in cells infected with wild-type SV40, showing that the effect seen with tsA mutants is not due to interference with initiation of DNA synthesis per se. In parallel infections at 41 degrees C, the amount of early RNA per copy of viral DNA was as much as 2,000 times greater with tsA58 than with wild-type SV40, even though there was no replication of the tsA58 DNA. Synthesis of late RNA could not be detected during the first 20 h of an infection by either virus at 32 degrees C, indicating that late and early transcription are under different control. In three cell lines transformed by tsA mutants, the amount of early RNA increased moderately after a shift from 32 to 41 degrees C, whereas with homologous cells transformed by wild-type virus, the amount of early RNA decreased, indicating that the A protein may be able to repress transcription of integrated SV40 DNA. All the observations are consistent with a simple model in which the binding of A protein at the origin of replication blocks either binding of RNA polymerase to the early promoter or its progress through the early gene(s)."}
{"id": "PMID:198576", "title": "Electron microscopic characterization of the defectiveness of a temperature-sensitive mutant of Moloney murine leukemia virus restricted in assembly.", "content": "The effect of temperature shiftdown on the assembly of ts3 virions was investigated by both scanning (SEM) and transmission (TEM) electron microscopy. Ts3 is a spontaneous temperature-sensitive mutant of Moloney murine leukemia virus (Mo-MuLV) which previous studies indicated to be defective in assembly or release of the virions. In the present study, both SEM and TEM revealed the following: (i) there were more cell-associated virions in ts3-infected cells grown at the nonpermissive temperature (39 degrees C) than either in cells grown at the permissive temperature (34 degrees C) or in wild-type MuLV-infected cells grown at 39 degrees C; (ii) there were more normal single particles than multiploids (virions with two or more pieces of genomic RNA) in ts3-infected cells grown at the nonpermissive temperature; (iii) there were more multiploids in ts3-infected cells grown at the nonpermissive temperature than either in cells grown at the permissive temperature or in wild-type MuLV-infected cells grown at the nonpermissive temperature; (iv) upon temperature shift from 39 to 34 degrees C, about 90% of the cell-associated virions dissociated from the cell surface. TEM studies also indicated that upon temperature shiftdown, virion assembly rapidly occurred. The above observations suggest that faulty assembly, which results in the production of multiploids, may not be the reason why ts3 virions accumulate on the cell surface at the nonpermissive temperature. The relatively higher proportion of multiploids found in ts3-infected cells grown at 39 degrees C compared with those grown at 34 degrees C may be due to the higher density of budding virions at the cell surface at the nonpermissive temperature, which increases the possibility of two or more particles assembling close to one another. The accumulation of ts3 virions in all stages of assembly at the nonpermissive temperature, together with the fact that rapid assembly and release of ts3 virions occurred on temperature shiftdown, indicates that virion assembly is restricted after it has been initiated. The probable role of altered glycoprotein(s) in restricting virion assembly is discussed.", "contents": "Electron microscopic characterization of the defectiveness of a temperature-sensitive mutant of Moloney murine leukemia virus restricted in assembly. The effect of temperature shiftdown on the assembly of ts3 virions was investigated by both scanning (SEM) and transmission (TEM) electron microscopy. Ts3 is a spontaneous temperature-sensitive mutant of Moloney murine leukemia virus (Mo-MuLV) which previous studies indicated to be defective in assembly or release of the virions. In the present study, both SEM and TEM revealed the following: (i) there were more cell-associated virions in ts3-infected cells grown at the nonpermissive temperature (39 degrees C) than either in cells grown at the permissive temperature (34 degrees C) or in wild-type MuLV-infected cells grown at 39 degrees C; (ii) there were more normal single particles than multiploids (virions with two or more pieces of genomic RNA) in ts3-infected cells grown at the nonpermissive temperature; (iii) there were more multiploids in ts3-infected cells grown at the nonpermissive temperature than either in cells grown at the permissive temperature or in wild-type MuLV-infected cells grown at the nonpermissive temperature; (iv) upon temperature shift from 39 to 34 degrees C, about 90% of the cell-associated virions dissociated from the cell surface. TEM studies also indicated that upon temperature shiftdown, virion assembly rapidly occurred. The above observations suggest that faulty assembly, which results in the production of multiploids, may not be the reason why ts3 virions accumulate on the cell surface at the nonpermissive temperature. The relatively higher proportion of multiploids found in ts3-infected cells grown at 39 degrees C compared with those grown at 34 degrees C may be due to the higher density of budding virions at the cell surface at the nonpermissive temperature, which increases the possibility of two or more particles assembling close to one another. The accumulation of ts3 virions in all stages of assembly at the nonpermissive temperature, together with the fact that rapid assembly and release of ts3 virions occurred on temperature shiftdown, indicates that virion assembly is restricted after it has been initiated. The probable role of altered glycoprotein(s) in restricting virion assembly is discussed."}
{"id": "PMID:198577", "title": "Anatomy of herpes simplex virus DNA. IX. Apparent exclusion of some parental DNA arrangements in the generation of intertypic (HSV-1 X HSV-2) recombinants.", "content": "We are reporting the physical location of parental DNA sequences in 28 recombinants produced by crossing herpes simplex viruses (HSV) 1 and 2. The parental crosses were of two kinds. In the first, temperature-sensitive mutants of HSV-1 and HSV-2 were crossed to produce wild-type recombinants. In the second, temperature-sensitive mutants of HSV-1 rendered resistant to phosphonoacetic acid were crossed with wild-type HSV-2, and recombinants that multiplied at nonpermissive temperature and were resistant to the drug were selected. The DNAs of the recombinants were mapped with XbaI, EcoRI, HpaI, HsuI, BglII, and, in some instances, KpnI restriction endonucleases. The results were as follows. (i) We established the colinear arrangements of HSV-1 and HSV-2 DNAs. (ii) There was extensive interchange of genomic regions, ranging from the exchange or the entire L of S component of HSV DNA to substitutions of regions within the same component. In some recombinants, the reiterated sequences ab and ac bracketing the L and S components of HSV DNA were heterotypic. Most recombinants grew well and showed no obvious defects. (iii) The number of crossover events ranged from one to as many as six. Although crossover events occurred throughout the DNA, some clustering of crossover events was observed. (iv) Analysis of recombinants permitted localization of several markers used in this study and appears to be a useful technique for marker mapping. (v) As previously reported, HSV DNA consists of four populations, differing in relative orientation of the L and S components. All recombinants could be displayed in one arrangement of L and S such that the number of crossover events was minimized. The data are consistent with the hypothesis that only one arrangement of the parental DNA participates in the generation of recombinants.", "contents": "Anatomy of herpes simplex virus DNA. IX. Apparent exclusion of some parental DNA arrangements in the generation of intertypic (HSV-1 X HSV-2) recombinants. We are reporting the physical location of parental DNA sequences in 28 recombinants produced by crossing herpes simplex viruses (HSV) 1 and 2. The parental crosses were of two kinds. In the first, temperature-sensitive mutants of HSV-1 and HSV-2 were crossed to produce wild-type recombinants. In the second, temperature-sensitive mutants of HSV-1 rendered resistant to phosphonoacetic acid were crossed with wild-type HSV-2, and recombinants that multiplied at nonpermissive temperature and were resistant to the drug were selected. The DNAs of the recombinants were mapped with XbaI, EcoRI, HpaI, HsuI, BglII, and, in some instances, KpnI restriction endonucleases. The results were as follows. (i) We established the colinear arrangements of HSV-1 and HSV-2 DNAs. (ii) There was extensive interchange of genomic regions, ranging from the exchange or the entire L of S component of HSV DNA to substitutions of regions within the same component. In some recombinants, the reiterated sequences ab and ac bracketing the L and S components of HSV DNA were heterotypic. Most recombinants grew well and showed no obvious defects. (iii) The number of crossover events ranged from one to as many as six. Although crossover events occurred throughout the DNA, some clustering of crossover events was observed. (iv) Analysis of recombinants permitted localization of several markers used in this study and appears to be a useful technique for marker mapping. (v) As previously reported, HSV DNA consists of four populations, differing in relative orientation of the L and S components. All recombinants could be displayed in one arrangement of L and S such that the number of crossover events was minimized. The data are consistent with the hypothesis that only one arrangement of the parental DNA participates in the generation of recombinants."}
{"id": "PMID:198578", "title": "Human cytomegalovirus genome: partial denaturation map and organization of genome sequences.", "content": "Contour-length measurements of both nondenatured and partially denatured DNA from purified extracellular human cytomegalovirus indicate that more than one size class of viral DNA is encapsidated. In addition to a size class averaging about 100 x 10(6) daltons, a much less abundant class of larger viral DNA molecules, 150 x 10(6) to 155 x 10(6) daltons, was extracted from purified extracellular virus. As predicted by melting-curve analysis, partial denaturation of human cytomegalovirus DNA generates denaturation maps showing distinctive adenine plus thymidine (A+T)-rich and guanine plus cytosine (G+C)-rich localizations. Alignment of partial denaturation maps of both 100 x 10(6)- and 150 x 10(6)- to 155 x 10(6)-dalton molecules from maximum overlap of common A+T- and G+C-rich zones clearly shows six unique zones contained in a length equal to the longest class, 150 x 10(6) to 155 x 10(6) daltons. However, various alignments of the smaller class of the molecules within the confines of the approximately 100 x 10(6)-dalton-length equivalent are nondistinctive. Of the six unique A+T- and G+C-rich zones, five are linked in a specific sequence and maintain the same relative orientation; these features indicate the absence of major inversions within these zones. The sixth unique zone may occur at either end of this five-zone series, but it was never found at both ends of the same molecule. Additionally, this terminal zone appears to undergo complete inversions at least at one end of the alignment, and perhaps at both. These data indicate that 150 x 10(6)- to 155 x 10(6)-dalton molecules comprise human cytomegalovirus-specific genetic information.", "contents": "Human cytomegalovirus genome: partial denaturation map and organization of genome sequences. Contour-length measurements of both nondenatured and partially denatured DNA from purified extracellular human cytomegalovirus indicate that more than one size class of viral DNA is encapsidated. In addition to a size class averaging about 100 x 10(6) daltons, a much less abundant class of larger viral DNA molecules, 150 x 10(6) to 155 x 10(6) daltons, was extracted from purified extracellular virus. As predicted by melting-curve analysis, partial denaturation of human cytomegalovirus DNA generates denaturation maps showing distinctive adenine plus thymidine (A+T)-rich and guanine plus cytosine (G+C)-rich localizations. Alignment of partial denaturation maps of both 100 x 10(6)- and 150 x 10(6)- to 155 x 10(6)-dalton molecules from maximum overlap of common A+T- and G+C-rich zones clearly shows six unique zones contained in a length equal to the longest class, 150 x 10(6) to 155 x 10(6) daltons. However, various alignments of the smaller class of the molecules within the confines of the approximately 100 x 10(6)-dalton-length equivalent are nondistinctive. Of the six unique A+T- and G+C-rich zones, five are linked in a specific sequence and maintain the same relative orientation; these features indicate the absence of major inversions within these zones. The sixth unique zone may occur at either end of this five-zone series, but it was never found at both ends of the same molecule. Additionally, this terminal zone appears to undergo complete inversions at least at one end of the alignment, and perhaps at both. These data indicate that 150 x 10(6)- to 155 x 10(6)-dalton molecules comprise human cytomegalovirus-specific genetic information."}
{"id": "PMID:198579", "title": "Physical and genetic characterization of deletion mutants of simian virus 40 constructed in vitro.", "content": "Mutants of simian virus 40 (SV40), with deletions ranging in size from fewer than 3 to 750 base pairs located throughout the SV40 genome, were obtained by infecting CV-1P cells with linear SV40 DNA and DNA of an appropriate helper virus. The linear DNA was obtained by complete cleavage of closed circular DNA with Hae II or Bam HI endonuclease or partial cleavage with either Hae III endonuclease or nuclease S1, followed, in some cases, by mild digestion with phage lambda 5' -exonuclease. The following mutants with deletions in the late region of the SV40 genome were obtained and characterized. Ten, containing deletions at the Hae II endonuclease site (map location 0.83), define a new genetic complementation group, E, grow extremely slowly without helper virus, and cause alterations only in VP2. Two mutants with deletions in the region 0.92 to 0.945 affect both VP2 and VP3, demonstrating that VP3 shares sequences with the C-terminal portion of VP2. The mutant with a deletion at 0.93 is the first deletion mutant in the D complementation group and is also temperature sensitive; the mutant with a deletion at 0.94 is viable and grows normally. Three mutants with deletions at the EcoRI endonuclease site (0/1.0) and eleven with deletions at the BamHI endonuclease site (0.15) fall into the B/C complementation group. Six additional mutants with deletions at the BamHI endonuclease site are viable, growing more slowly than wild type. VP1 is the only polypeptide affected by mutants in the B/C group. A mutant with a deletion of the region 0.72 to 0.80 has a polar effect, failing to express the E, D, and B/C genes. Mutants with deletions in the early region (0.67 counterclockwise to 0.17) at 0.66 to 0.59, 0.48, 0.47, 0.33, and 0.285 to 0.205 are all members of the A complementation group. Thus, the A gene is the only viral gene in the early region whose expression is necessary for productive infection of permissive cells. Since mutants with deletions in the region 0.59 to 0.54 are viable, two separate regions are essential for expression of the gene A function: 0.66 to 0.59 and 0.54 to 0.21. Mutants with deletions at 0.21 and 0.18 are viable. Approximate map locations of SV40 genes and possible models for their regulation are discussed.", "contents": "Physical and genetic characterization of deletion mutants of simian virus 40 constructed in vitro. Mutants of simian virus 40 (SV40), with deletions ranging in size from fewer than 3 to 750 base pairs located throughout the SV40 genome, were obtained by infecting CV-1P cells with linear SV40 DNA and DNA of an appropriate helper virus. The linear DNA was obtained by complete cleavage of closed circular DNA with Hae II or Bam HI endonuclease or partial cleavage with either Hae III endonuclease or nuclease S1, followed, in some cases, by mild digestion with phage lambda 5' -exonuclease. The following mutants with deletions in the late region of the SV40 genome were obtained and characterized. Ten, containing deletions at the Hae II endonuclease site (map location 0.83), define a new genetic complementation group, E, grow extremely slowly without helper virus, and cause alterations only in VP2. Two mutants with deletions in the region 0.92 to 0.945 affect both VP2 and VP3, demonstrating that VP3 shares sequences with the C-terminal portion of VP2. The mutant with a deletion at 0.93 is the first deletion mutant in the D complementation group and is also temperature sensitive; the mutant with a deletion at 0.94 is viable and grows normally. Three mutants with deletions at the EcoRI endonuclease site (0/1.0) and eleven with deletions at the BamHI endonuclease site (0.15) fall into the B/C complementation group. Six additional mutants with deletions at the BamHI endonuclease site are viable, growing more slowly than wild type. VP1 is the only polypeptide affected by mutants in the B/C group. A mutant with a deletion of the region 0.72 to 0.80 has a polar effect, failing to express the E, D, and B/C genes. Mutants with deletions in the early region (0.67 counterclockwise to 0.17) at 0.66 to 0.59, 0.48, 0.47, 0.33, and 0.285 to 0.205 are all members of the A complementation group. Thus, the A gene is the only viral gene in the early region whose expression is necessary for productive infection of permissive cells. Since mutants with deletions in the region 0.59 to 0.54 are viable, two separate regions are essential for expression of the gene A function: 0.66 to 0.59 and 0.54 to 0.21. Mutants with deletions at 0.21 and 0.18 are viable. Approximate map locations of SV40 genes and possible models for their regulation are discussed."}
{"id": "PMID:198580", "title": "Structure and formation of circular dimers of simian virus 40 DNA.", "content": "Most of the viral DNA extracted from simian virus 40 (SV40)-infected African green monkey kidney cells consists of circular molecules about 5.3 kilobases in contour length. However, about 1% of the viral DNA was found to occur as closed circular dimers that appeared to be formed, preferentially, late in infection. The monomeric units of dimers were organized in a head-to-tail, tandem arrangement; moreover, the monomeric units were not defective; i.e., they lacked deletions or other rearrangements. After infections with dimer DNA, nondefective monomers were formed. These findings suggest that dimers are not intermediates in the production of defective SV40 genomes. The majority of the dimers formed in mixed infections with two mutants were homodimers, but about 5% of the circular dimers were heterodimers and must have arisen by intermolecular recombination.", "contents": "Structure and formation of circular dimers of simian virus 40 DNA. Most of the viral DNA extracted from simian virus 40 (SV40)-infected African green monkey kidney cells consists of circular molecules about 5.3 kilobases in contour length. However, about 1% of the viral DNA was found to occur as closed circular dimers that appeared to be formed, preferentially, late in infection. The monomeric units of dimers were organized in a head-to-tail, tandem arrangement; moreover, the monomeric units were not defective; i.e., they lacked deletions or other rearrangements. After infections with dimer DNA, nondefective monomers were formed. These findings suggest that dimers are not intermediates in the production of defective SV40 genomes. The majority of the dimers formed in mixed infections with two mutants were homodimers, but about 5% of the circular dimers were heterodimers and must have arisen by intermolecular recombination."}
{"id": "PMID:198581", "title": "[125I]deoxycytidine used in a rapid, sensitive, and specific assay for herpes simplex virus type 1 thymidine kinase.", "content": "[125I]deoxycytidine was a good substrate for herpes simplex virus type 1 thymidine kinase (TK), whereas [125I]deoxycytidine was a very poor substrate for cellular TK. Simple, sensitive, and specific assays for viral TK could be carried out in vivo and in vitro even in the presence of cell TK. Autoradiographic detection of incorporated [125I]deoxycytidine provided a rapid and simple method for detection of and screening for viral TK in infected as well as viral TK-transformed cells.", "contents": "[125I]deoxycytidine used in a rapid, sensitive, and specific assay for herpes simplex virus type 1 thymidine kinase. [125I]deoxycytidine was a good substrate for herpes simplex virus type 1 thymidine kinase (TK), whereas [125I]deoxycytidine was a very poor substrate for cellular TK. Simple, sensitive, and specific assays for viral TK could be carried out in vivo and in vitro even in the presence of cell TK. Autoradiographic detection of incorporated [125I]deoxycytidine provided a rapid and simple method for detection of and screening for viral TK in infected as well as viral TK-transformed cells."}
{"id": "PMID:198582", "title": "Relationship between the methionine tryptic peptides of simian virus 40 and BK virus tumor antigens.", "content": "The monomer form of BK virus (BKV) tumor antigen (T Ag) was immunoprecipitated from extracts of BKV-transformed cells and had a molecular weight of approximately 113,000. This compared with 97,000 for the molecular weight of either BKV or simian virus 40 (SV40) T Ag from lytically infected cells. The SV40 and BKV T Ag's from productively infected cells were compared by examining their methionine-labeled tryptic peptides. Out of a total of 20 SV40-and 21 BKV-specific peptides, there were seven pairs of similar peptides on the basis of ion-exchange chromatography, These coeluting peptides contained approximately 25 to 30% of the total methionine radioactivity. Similar results were obtained when the tryptic peptides of SV40 T Ag from lytically infected cells were compared with those of BKV T Ag from virally transformed cells.", "contents": "Relationship between the methionine tryptic peptides of simian virus 40 and BK virus tumor antigens. The monomer form of BK virus (BKV) tumor antigen (T Ag) was immunoprecipitated from extracts of BKV-transformed cells and had a molecular weight of approximately 113,000. This compared with 97,000 for the molecular weight of either BKV or simian virus 40 (SV40) T Ag from lytically infected cells. The SV40 and BKV T Ag's from productively infected cells were compared by examining their methionine-labeled tryptic peptides. Out of a total of 20 SV40-and 21 BKV-specific peptides, there were seven pairs of similar peptides on the basis of ion-exchange chromatography, These coeluting peptides contained approximately 25 to 30% of the total methionine radioactivity. Similar results were obtained when the tryptic peptides of SV40 T Ag from lytically infected cells were compared with those of BKV T Ag from virally transformed cells."}
{"id": "PMID:198583", "title": "Prolongation of herpes simplex virus latency in cultured human cells by temperature elevation.", "content": "Treatment of herpes simplex virus type 2 (HSV-2)-infected human fibroblast cells with cytosine arabinoside (ara-C) at 25 microgram/ml resulted in complete inhibition of virus replication. Removal of ara-C after 7 days of treatment ultimately resulted in renewed virus replication, but after a delay of at least 5 days. If however, the temperature was elevated from 37 degrees C to 39.5 to 40 degrees C at the time of ara-C reversal, infectious HSV-2 did not reappear. As long as the cultures were maintained at 39.5 to 40 degrees C (up to at least 128 days), HSV-2 was latent and infectious virus was undetectable. If the temperature was reduced to 37 degrees C at any time during the latent period, infectious virus was always reactivated, but only after a period of incubation at 37 degrees C of a least 11 days. Infectious-center assays performed with latent cultures indicated that only a very small fraction of cells could reactivate virus. The infectious-center titer did not show significant changes during much of the period of latency. This seemed to argue against the possibility that the latent cultures were synthesizing very small amounts of infectious virus. Additional studies were aimed at determining the minimum incubation period at 37 degrees C required to reactivate infectious HSV-2. Latent cultures reduced from 39.5 to 40 degrees C to 37 degrees C for less than 96 h did not yield infectious HSV-2, but those incubated at 37 degrees C for 96 h or more did.", "contents": "Prolongation of herpes simplex virus latency in cultured human cells by temperature elevation. Treatment of herpes simplex virus type 2 (HSV-2)-infected human fibroblast cells with cytosine arabinoside (ara-C) at 25 microgram/ml resulted in complete inhibition of virus replication. Removal of ara-C after 7 days of treatment ultimately resulted in renewed virus replication, but after a delay of at least 5 days. If however, the temperature was elevated from 37 degrees C to 39.5 to 40 degrees C at the time of ara-C reversal, infectious HSV-2 did not reappear. As long as the cultures were maintained at 39.5 to 40 degrees C (up to at least 128 days), HSV-2 was latent and infectious virus was undetectable. If the temperature was reduced to 37 degrees C at any time during the latent period, infectious virus was always reactivated, but only after a period of incubation at 37 degrees C of a least 11 days. Infectious-center assays performed with latent cultures indicated that only a very small fraction of cells could reactivate virus. The infectious-center titer did not show significant changes during much of the period of latency. This seemed to argue against the possibility that the latent cultures were synthesizing very small amounts of infectious virus. Additional studies were aimed at determining the minimum incubation period at 37 degrees C required to reactivate infectious HSV-2. Latent cultures reduced from 39.5 to 40 degrees C to 37 degrees C for less than 96 h did not yield infectious HSV-2, but those incubated at 37 degrees C for 96 h or more did."}
{"id": "PMID:198584", "title": "Temperature-sensitive mutants of human cytomegalovirus.", "content": "Eight temperature-sensitive mutants of human cytomegalovirus have been isolated after mutagenesis with nitrosoguanidine. Three of these mutants have been classified into three separate complementation groups and are capable of synthesizing virus DNA at the nonpermissive temperature (39.5 degrees C). Two others appear unable to synthesize virus DNA at the elevated temperature.", "contents": "Temperature-sensitive mutants of human cytomegalovirus. Eight temperature-sensitive mutants of human cytomegalovirus have been isolated after mutagenesis with nitrosoguanidine. Three of these mutants have been classified into three separate complementation groups and are capable of synthesizing virus DNA at the nonpermissive temperature (39.5 degrees C). Two others appear unable to synthesize virus DNA at the elevated temperature."}
{"id": "PMID:198585", "title": "Size and genetic content of viral RNAs in avian oncovirus-infected cells.", "content": "Viral complementary DNA (cDNA) sequences corresponding to the gag, pol, env, src, and c regions of the Rous sarcoma virus genome were selected by hybridizing viral cDNA to RNA from viruses that lack the env or src gene or to polyadenylic acid [poly(A)]-containing RNA fragments of different lengths and isolating either hybridized or unhybridized DNA. The specificities, genetic complexities, and map locations of the selected cDNA's were shown to be in good agreement with the size and map locations of the corresponding viral genes. Analyses of virus-specific RNA, using the specific cDNA's as molecular probes, demonstrated that oncovirus-infected cells contained genome-length (30-40S) RNA plus either one or two species of subgenome-length viral RNA. The size and genetic content of these RNAs varied, depending on the genetic makeup of the infecting virus, but in each case the smaller RNAs contained only sequences located near the 3' end of the viral genome. Three RNA species were detected in Schmidt-Ruppin Rous sarcoma virus-infected cells: 39S (genome-length) RNA; 28S RNA, with an apparent sequence of env-src-c-poly(A); and 21S RNA, with an apparent sequence of src-c-poly(A). Cells infected with the Bryan high-titer strain of Rous sarcoma virus, which lacks the env gene, contained genome-length (35S) RNA and 21S src-specific RNA, but not the 28S RNA species. Leukosis virus-infected cells contained two detectable RNA species: 35S (genome-length) RNA and 21S RNA, with apparent sequence env-c-poly(A). Since gag and pol sequences were detected only in genome-length RNAs, it seems likely that the full-length transcripts function as mRNA for these two genes. The 28S and 21S RNAs could be the active messengers for the env and src genes. Analyses of sequence homologies among nucleic acids of different avian oncoviruses demonstrated substantial similarities within most of the genetic regions of these viruses. However, the \"common\" region of Rous-associated virus-0, an endogenous virus, was found to differ significantly from that of the other viruses tested.", "contents": "Size and genetic content of viral RNAs in avian oncovirus-infected cells. Viral complementary DNA (cDNA) sequences corresponding to the gag, pol, env, src, and c regions of the Rous sarcoma virus genome were selected by hybridizing viral cDNA to RNA from viruses that lack the env or src gene or to polyadenylic acid [poly(A)]-containing RNA fragments of different lengths and isolating either hybridized or unhybridized DNA. The specificities, genetic complexities, and map locations of the selected cDNA's were shown to be in good agreement with the size and map locations of the corresponding viral genes. Analyses of virus-specific RNA, using the specific cDNA's as molecular probes, demonstrated that oncovirus-infected cells contained genome-length (30-40S) RNA plus either one or two species of subgenome-length viral RNA. The size and genetic content of these RNAs varied, depending on the genetic makeup of the infecting virus, but in each case the smaller RNAs contained only sequences located near the 3' end of the viral genome. Three RNA species were detected in Schmidt-Ruppin Rous sarcoma virus-infected cells: 39S (genome-length) RNA; 28S RNA, with an apparent sequence of env-src-c-poly(A); and 21S RNA, with an apparent sequence of src-c-poly(A). Cells infected with the Bryan high-titer strain of Rous sarcoma virus, which lacks the env gene, contained genome-length (35S) RNA and 21S src-specific RNA, but not the 28S RNA species. Leukosis virus-infected cells contained two detectable RNA species: 35S (genome-length) RNA and 21S RNA, with apparent sequence env-c-poly(A). Since gag and pol sequences were detected only in genome-length RNAs, it seems likely that the full-length transcripts function as mRNA for these two genes. The 28S and 21S RNAs could be the active messengers for the env and src genes. Analyses of sequence homologies among nucleic acids of different avian oncoviruses demonstrated substantial similarities within most of the genetic regions of these viruses. However, the \"common\" region of Rous-associated virus-0, an endogenous virus, was found to differ significantly from that of the other viruses tested."}
{"id": "PMID:198586", "title": "Genetic variation in the RNA transcripts of endogenous virus genes in uninfected chicken cells.", "content": "Uninfected cells from two different phenotypes of chicken embryos express significant amounts of endogenous viral information, though they do not produce virus particles. Cells of the phenotype gs(+)chf(+) are positive for both group-specific (gs) antigens and chicken helper factor (chf) activity, whereas cells of a second phenotype, gs(L)chf(+)(h(E)), demonstrate noncoordinate expression of these two viral activities (very low amounts of gs antigens, but extremely high helper activity). RNA from these cells was analyzed to determine the size, genetic content, and relative abundance of virus-specific RNAs in cells of each phenotype. Two major size classes of polyadenylic acid-containing RNA, homologous to the avian leukosis virus genome, were detectable in cells of both types. The larger RNA, which contained most of the sequences of the leukosis virus genome, was of different sizes in the two phenotypes, 31S in gs(+)chf(+) cells but 35S in the noncoordinate cell type. Analysis of the viral RNA with gene-specific complementary DNA probes revealed the following characteristics. (i) The 31S RNA appeared to lack portions of the gag and pol genes. (ii) A smaller RNA species, which sedimented at 21S in both cell types, was a transcript of the 3'-proximal portion of the viral genome, consisting of the env gene and the \"common\" sequences. (iii) The amount of env-specific RNA in the 21S region was more than six times higher in the noncoordinate cell type than in the gs(+)chf(+) cells; this difference was concordant with the 5- to 10-fold higher chf activity in the noncoordinate cells. (iv) The endogenous viral RNA in uninfected cells and the RNA from Rous-associated virus-0 virions hybridized only partially with DNA complementary to the common region of the Rous-associated virus-2 genome, whereas the RNA of all exogenous viruses tested hybridized almost completely to this complementary DNA. Small amounts of src-specific polyadenylated RNA were also present in uninfected chicken cells. This RNA sedimented as a single peak at 26S and was not covalently linked to any other identifiable virus-specific RNA sequences. The amount of src RNA was the same in the above two types of expression-positive cells and also in cells that were gs(-)chf(-), indicating that the transcription of the cellular sequences homologous to the src gene is independent of the transcription of the other endogenous viral genes.", "contents": "Genetic variation in the RNA transcripts of endogenous virus genes in uninfected chicken cells. Uninfected cells from two different phenotypes of chicken embryos express significant amounts of endogenous viral information, though they do not produce virus particles. Cells of the phenotype gs(+)chf(+) are positive for both group-specific (gs) antigens and chicken helper factor (chf) activity, whereas cells of a second phenotype, gs(L)chf(+)(h(E)), demonstrate noncoordinate expression of these two viral activities (very low amounts of gs antigens, but extremely high helper activity). RNA from these cells was analyzed to determine the size, genetic content, and relative abundance of virus-specific RNAs in cells of each phenotype. Two major size classes of polyadenylic acid-containing RNA, homologous to the avian leukosis virus genome, were detectable in cells of both types. The larger RNA, which contained most of the sequences of the leukosis virus genome, was of different sizes in the two phenotypes, 31S in gs(+)chf(+) cells but 35S in the noncoordinate cell type. Analysis of the viral RNA with gene-specific complementary DNA probes revealed the following characteristics. (i) The 31S RNA appeared to lack portions of the gag and pol genes. (ii) A smaller RNA species, which sedimented at 21S in both cell types, was a transcript of the 3'-proximal portion of the viral genome, consisting of the env gene and the \"common\" sequences. (iii) The amount of env-specific RNA in the 21S region was more than six times higher in the noncoordinate cell type than in the gs(+)chf(+) cells; this difference was concordant with the 5- to 10-fold higher chf activity in the noncoordinate cells. (iv) The endogenous viral RNA in uninfected cells and the RNA from Rous-associated virus-0 virions hybridized only partially with DNA complementary to the common region of the Rous-associated virus-2 genome, whereas the RNA of all exogenous viruses tested hybridized almost completely to this complementary DNA. Small amounts of src-specific polyadenylated RNA were also present in uninfected chicken cells. This RNA sedimented as a single peak at 26S and was not covalently linked to any other identifiable virus-specific RNA sequences. The amount of src RNA was the same in the above two types of expression-positive cells and also in cells that were gs(-)chf(-), indicating that the transcription of the cellular sequences homologous to the src gene is independent of the transcription of the other endogenous viral genes."}
{"id": "PMID:198587", "title": "Visna virus RNA synthesis.", "content": "Visna is a classical slow infection in which virus characteristically persists in the face of the host immune response. The agent of this disease belongs to the retravirus group. The persistence of infection and the slow spread of virus are at least in part a consequence of restriction of the expression of virus genetic information in tissues of an infected animal (A. T. Haase et al., Science 195:175-177, 1977), but the point at which the virus life cycle is interrupted in vivo and the mechanism of restriction are unknown. We have embarked on a molecular analysis of restriction, focusing first on transcription. In this paper we have established the levels of viral RNA synthesis under permissive conditions, as a base line for subsequent studies in vivo. We show that (i) uninfected cells do not contain RNA sequences related to the visna virus genome, (ii) parental RNA is rapidly transported to the nucleus of the infected cell, (iii) virus RNA is synthesized in the nucleus and then transported to the cytoplasm (iv) synthesis of RNA proceeds mostly exponentially to reach levels of about 4,000 copies per cell at the end of the growth cycle, (v) nuclear and cytoplasmic RNA sediment in two size classes, 35S and 10-20S, (vi) viral mRNA  has the same polarity as genome RNA and also sediments in two size classes of 35S and 10-20S.", "contents": "Visna virus RNA synthesis. Visna is a classical slow infection in which virus characteristically persists in the face of the host immune response. The agent of this disease belongs to the retravirus group. The persistence of infection and the slow spread of virus are at least in part a consequence of restriction of the expression of virus genetic information in tissues of an infected animal (A. T. Haase et al., Science 195:175-177, 1977), but the point at which the virus life cycle is interrupted in vivo and the mechanism of restriction are unknown. We have embarked on a molecular analysis of restriction, focusing first on transcription. In this paper we have established the levels of viral RNA synthesis under permissive conditions, as a base line for subsequent studies in vivo. We show that (i) uninfected cells do not contain RNA sequences related to the visna virus genome, (ii) parental RNA is rapidly transported to the nucleus of the infected cell, (iii) virus RNA is synthesized in the nucleus and then transported to the cytoplasm (iv) synthesis of RNA proceeds mostly exponentially to reach levels of about 4,000 copies per cell at the end of the growth cycle, (v) nuclear and cytoplasmic RNA sediment in two size classes, 35S and 10-20S, (vi) viral mRNA  has the same polarity as genome RNA and also sediments in two size classes of 35S and 10-20S."}
{"id": "PMID:198588", "title": "Crossed immunoelectrophoretic studies of the solubility immunogenicity of herpes simplex virus antigens.", "content": "The nonionic detergent Triton X-100 was capable of solubilizing 90% of the protein content in herpes simplex virus (HSV)-infected rabbit cornea cells. The solubilized HSV antigens formed well-characterized precipitates by crossed immunoelectrophoresis in Triton X-100-containing agarose gel, allowing both identification and relative quantitation. Water-soluble and detergent-requiring HSV antigens were identified by different solubilization procedures in buffer with and without detergent. Five glycoprotein antigens were solubilized only in the presence of detergent, indicating their membrane-bound state. One non-glycosylated antigen was present in both a water-soluble and a membrane-bound form. Based upon the crossed immunoelectrophoretic precipitating patterns of Triton X-100-solubilized HSV antigens, it has been estimated that infected cells yield an amount of virus-specific protein equivalent to 2,000 enveloped virions per cell. Rabbits inoculated intracutaneously with Triton X-100-solubilized HSV antigens developed neutralizing antibodies against HSV almost as effectively as rabbits with an active HSV infection. Precipitins against individual HSV antigens in sera from rabbits infected with HSV and immunized with the Triton X-100-solubilized HSV antigens were assayed by the crossed immunoelectrophoretic technique. Sera from infected rabbits reacted more strongly and with a higher number of HSV antigens than sera from immunized rabbits.", "contents": "Crossed immunoelectrophoretic studies of the solubility immunogenicity of herpes simplex virus antigens. The nonionic detergent Triton X-100 was capable of solubilizing 90% of the protein content in herpes simplex virus (HSV)-infected rabbit cornea cells. The solubilized HSV antigens formed well-characterized precipitates by crossed immunoelectrophoresis in Triton X-100-containing agarose gel, allowing both identification and relative quantitation. Water-soluble and detergent-requiring HSV antigens were identified by different solubilization procedures in buffer with and without detergent. Five glycoprotein antigens were solubilized only in the presence of detergent, indicating their membrane-bound state. One non-glycosylated antigen was present in both a water-soluble and a membrane-bound form. Based upon the crossed immunoelectrophoretic precipitating patterns of Triton X-100-solubilized HSV antigens, it has been estimated that infected cells yield an amount of virus-specific protein equivalent to 2,000 enveloped virions per cell. Rabbits inoculated intracutaneously with Triton X-100-solubilized HSV antigens developed neutralizing antibodies against HSV almost as effectively as rabbits with an active HSV infection. Precipitins against individual HSV antigens in sera from rabbits infected with HSV and immunized with the Triton X-100-solubilized HSV antigens were assayed by the crossed immunoelectrophoretic technique. Sera from infected rabbits reacted more strongly and with a higher number of HSV antigens than sera from immunized rabbits."}
{"id": "PMID:198589", "title": "Further biochemical characterization, including the detection of surface glycoproteins, of human, calf, and simian rotaviruses.", "content": "Polyacrylamide gel electrophoretic analysis of purified preparation of the simian rotavirus SA-11 indicated eight polypeptide components that migrated in a manner remarkably similar to those of the previously characterized human and calf rotaviruses. Analyses of preparations of single-shelled and double-shelled particles of human, calf, and simian an rotaviruses have also permitted assignment of the polypeptides to the inner or outer shells. The major components of the outer shells of each virus have been identified as glycoproteins, and the importance of this in terms of host cell specificity is discussed. Sensitivities of the various rotaviruses to acid, proteases, and glycosidases were also investigated.", "contents": "Further biochemical characterization, including the detection of surface glycoproteins, of human, calf, and simian rotaviruses. Polyacrylamide gel electrophoretic analysis of purified preparation of the simian rotavirus SA-11 indicated eight polypeptide components that migrated in a manner remarkably similar to those of the previously characterized human and calf rotaviruses. Analyses of preparations of single-shelled and double-shelled particles of human, calf, and simian an rotaviruses have also permitted assignment of the polypeptides to the inner or outer shells. The major components of the outer shells of each virus have been identified as glycoproteins, and the importance of this in terms of host cell specificity is discussed. Sensitivities of the various rotaviruses to acid, proteases, and glycosidases were also investigated."}
{"id": "PMID:198590", "title": "Genome of infectious bronchitis virus.", "content": "Techniques are described for the growth and rapid purification of the avian coronavirus infectious bronchitis virus (IBV). Purified IBV has a sedimentation coefficient of 320S and a buoyant density of 1.22 g/ml in sucrose-deuterium oxide equilibrium gradients. IBV RNA extracted by proteinase K in the presence of sodium dodecyl sulfate and further purified by phenol extraction and gradient centrifugation is single stranded and has a sedimentation coefficient of 64S, as determined by isokinetic gradient centrifugation. Analysis on sucrose gradients under both aqueous and denaturing conditions together with agarose gel electrophoresis in the presence of the chaotropic agent methylmercuric hydroxide gave a value of 8 X 10(6) for the moleclar weight of IBV RNA. This value was confirmed by RNase T1 fingerprinting, which also indicated that IBV RNA is haploid. No evidence was found of subunit structure in IBV RNA. From these results together with the recently reported observation that IBV RNA is infectious and contains a tract of polyadenylic acid (Lomniczi, J. Gen. Virol., in press), we conclude that the genome of the coronaviruses is a single continuous chain of about 23,000 mononucleotides that is of messenger polarity.", "contents": "Genome of infectious bronchitis virus. Techniques are described for the growth and rapid purification of the avian coronavirus infectious bronchitis virus (IBV). Purified IBV has a sedimentation coefficient of 320S and a buoyant density of 1.22 g/ml in sucrose-deuterium oxide equilibrium gradients. IBV RNA extracted by proteinase K in the presence of sodium dodecyl sulfate and further purified by phenol extraction and gradient centrifugation is single stranded and has a sedimentation coefficient of 64S, as determined by isokinetic gradient centrifugation. Analysis on sucrose gradients under both aqueous and denaturing conditions together with agarose gel electrophoresis in the presence of the chaotropic agent methylmercuric hydroxide gave a value of 8 X 10(6) for the moleclar weight of IBV RNA. This value was confirmed by RNase T1 fingerprinting, which also indicated that IBV RNA is haploid. No evidence was found of subunit structure in IBV RNA. From these results together with the recently reported observation that IBV RNA is infectious and contains a tract of polyadenylic acid (Lomniczi, J. Gen. Virol., in press), we conclude that the genome of the coronaviruses is a single continuous chain of about 23,000 mononucleotides that is of messenger polarity."}
{"id": "PMID:198591", "title": "Inflammatory fibrous histiocytoma presenting as a renal pelvic and bladder mass.", "content": "The first case of simultaneous presentation of a bladder and renal pelvic malignant fibrous histiocytoma is reported. Although only a small percentage of fibrous histiocytomas are malignant the lesion is extremely aggressive. Radiotherapy and chemotherapy have been used but only sporadic remissions have been reported. If the tumor is localized wide surgical excision is recommended.", "contents": "Inflammatory fibrous histiocytoma presenting as a renal pelvic and bladder mass. The first case of simultaneous presentation of a bladder and renal pelvic malignant fibrous histiocytoma is reported. Although only a small percentage of fibrous histiocytomas are malignant the lesion is extremely aggressive. Radiotherapy and chemotherapy have been used but only sporadic remissions have been reported. If the tumor is localized wide surgical excision is recommended."}
{"id": "PMID:198592", "title": "Wilms' tumor metastatic to the orbit.", "content": "In a 2 1/2-year-old boy, a proptotic right lower lid developed one year after a primary abdominal mass proved to be Wilms' tumor. An orbital abscess or fungal infection was considered because the child was receiving chemotherapy. However, echography demonstrated a firm orbital mass, delineated its dimensions, and showed destruction of the orbital floor. The biopsy specimen showed metastatic tumor cells. Lile neuroblastoma and certain hematologic and reticuloendothelial malignant neoplasms, Wilms' tumor may secondarily invade the ocular adnexa.", "contents": "Wilms' tumor metastatic to the orbit. In a 2 1/2-year-old boy, a proptotic right lower lid developed one year after a primary abdominal mass proved to be Wilms' tumor. An orbital abscess or fungal infection was considered because the child was receiving chemotherapy. However, echography demonstrated a firm orbital mass, delineated its dimensions, and showed destruction of the orbital floor. The biopsy specimen showed metastatic tumor cells. Lile neuroblastoma and certain hematologic and reticuloendothelial malignant neoplasms, Wilms' tumor may secondarily invade the ocular adnexa."}
{"id": "PMID:198594", "title": "Effects of angiotensin III (DES-1-asp-angiotensin II) and angiotensin III analogue (DES-1-asp-8-ile-angiotensin II) upon adrenal steroidogenesis and blood pressure.", "content": "Effects of angiotensin III and angiotensin III analogue upon adrenal steroidogenesis and blood pressure were studied in rats, rabbits and a man. Pressor effect of angiotensin III was about one fifth of that of angiotensin II in all the species. Degradation rate  of pressor effect of angiotensin III in plasma was more rapid than that of angiotensin II. Different from the effects of angiotensin III upon blood pressure, its effect upon aldosterone was similar to that of angiotensin II. The effect of angiotensin III upon other adrenal steroids, such as DOC and cortisol, however, seemed to be slightly less than that of angiotensin II. Angiotensin III producted an additive effect to that of ACTH, but it didn't produce an additive effect to that of angiotensin II. Angiotensin III analogue, itself, stimulated adrenal steroidogenesis, but it inhibited the effects of angiotensin III and angiotensin II upon aldosterone. Effects of ACTH upon plasma DOC and cortisol were not inhibited by angiotenesin III analogue, but the effect of ACTH upon aldosterone was blunted slightly.", "contents": "Effects of angiotensin III (DES-1-asp-angiotensin II) and angiotensin III analogue (DES-1-asp-8-ile-angiotensin II) upon adrenal steroidogenesis and blood pressure. Effects of angiotensin III and angiotensin III analogue upon adrenal steroidogenesis and blood pressure were studied in rats, rabbits and a man. Pressor effect of angiotensin III was about one fifth of that of angiotensin II in all the species. Degradation rate  of pressor effect of angiotensin III in plasma was more rapid than that of angiotensin II. Different from the effects of angiotensin III upon blood pressure, its effect upon aldosterone was similar to that of angiotensin II. The effect of angiotensin III upon other adrenal steroids, such as DOC and cortisol, however, seemed to be slightly less than that of angiotensin II. Angiotensin III producted an additive effect to that of ACTH, but it didn't produce an additive effect to that of angiotensin II. Angiotensin III analogue, itself, stimulated adrenal steroidogenesis, but it inhibited the effects of angiotensin III and angiotensin II upon aldosterone. Effects of ACTH upon plasma DOC and cortisol were not inhibited by angiotenesin III analogue, but the effect of ACTH upon aldosterone was blunted slightly."}
{"id": "PMID:198600", "title": "[The effect of natural and artificial light via the eye on the hormonal and metabolic balance of man (author's transl)].", "content": "Examinations of hormone levels in blind persons compared with almost blind and people with normal vision and hormone evaluation with increased artificial light exposure show a definite stimulating effect of light on the human hormonal balance. The effect of light is mediated by an intact perception of light by the eye over an \"energetic part\" of the visual pathway (Hollwich 1948) - hypothalamus - hypophysis - peripheral endocrine gland. Increasing the intensity of artificial light with \"neon-tubes\" (fluorescent tubes) leads to \"light stress\" proved by increased hormone production - especially the stress hormone Cortisol. The belief that artificial light is the same as natural light and that it can fully replace it, is inappropriate in the medical view and needs correction.", "contents": "[The effect of natural and artificial light via the eye on the hormonal and metabolic balance of man (author's transl)]. Examinations of hormone levels in blind persons compared with almost blind and people with normal vision and hormone evaluation with increased artificial light exposure show a definite stimulating effect of light on the human hormonal balance. The effect of light is mediated by an intact perception of light by the eye over an \"energetic part\" of the visual pathway (Hollwich 1948) - hypothalamus - hypophysis - peripheral endocrine gland. Increasing the intensity of artificial light with \"neon-tubes\" (fluorescent tubes) leads to \"light stress\" proved by increased hormone production - especially the stress hormone Cortisol. The belief that artificial light is the same as natural light and that it can fully replace it, is inappropriate in the medical view and needs correction."}
{"id": "PMID:198601", "title": "[Effect of clofibrate on lipoprotein-lipids in patients with type IV hyperlipoproteinaemia (author's transl)].", "content": "The effect of clofibrate treatment (1.5 g/day for four weeks) on triglycerides, cholesterol and phospholipids in very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) was investigated in 12 patients with type IV hyperlipoproteinaemia. The decrease of serum triglycerides was due to the reduction of VLDL-triglycerides. Furthermore, LDL-hypertriglyceridemia was normalised by clofibrate. -- There existed a significant decrease of VLDL- und HDL-cholesterol as well as of VLDL-phospholipids. The changes in LDL-cholesterol and LDL-phospholipids by clofibrate depended on their initial concentrations which were negatively correlated to the serum triglycerides before treatment. -- The normalisation of lipid concentrations in VLDL and LDI could be explained by a stimulated delipidation of the apo B-lipoproteins.", "contents": "[Effect of clofibrate on lipoprotein-lipids in patients with type IV hyperlipoproteinaemia (author's transl)]. The effect of clofibrate treatment (1.5 g/day for four weeks) on triglycerides, cholesterol and phospholipids in very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) was investigated in 12 patients with type IV hyperlipoproteinaemia. The decrease of serum triglycerides was due to the reduction of VLDL-triglycerides. Furthermore, LDL-hypertriglyceridemia was normalised by clofibrate. -- There existed a significant decrease of VLDL- und HDL-cholesterol as well as of VLDL-phospholipids. The changes in LDL-cholesterol and LDL-phospholipids by clofibrate depended on their initial concentrations which were negatively correlated to the serum triglycerides before treatment. -- The normalisation of lipid concentrations in VLDL and LDI could be explained by a stimulated delipidation of the apo B-lipoproteins."}
{"id": "PMID:198602", "title": "[Model studies on virus-induced tumors and their immunological treatment (author's transl)].", "content": "After a review of the general biological properties of C-type oncorna viruses, results are presented on the structure of an exogenous murine leukemia virus (FLV) and on the serobiological properties of its structural proteins. Our findings suggested a major role of the viral surface glycoprotein gp71 in immunological defense mechanisms. This was confirmed by vaccination experiments with isolated gp71 in mice. The induced immunity was highly specific and not operative against endogenous murine C-viruses belonging to other serotypes. Surprisingly the latter were found to be activated by the vaccination with gp71 of FLV. In heterologous animal species isolated FLV-gp71 induced the formation of broadly reacting antibodies. They were found to be effective in the therapy of infections with FLV in mice as well as with feline leukaemia virus in cats. Most impressive results were obtained with an antiserum prepared against feline leukaemia virus in a goat. This serum completely suppressed sarcomas induced by infection with feline sarcoma virus.", "contents": "[Model studies on virus-induced tumors and their immunological treatment (author's transl)]. After a review of the general biological properties of C-type oncorna viruses, results are presented on the structure of an exogenous murine leukemia virus (FLV) and on the serobiological properties of its structural proteins. Our findings suggested a major role of the viral surface glycoprotein gp71 in immunological defense mechanisms. This was confirmed by vaccination experiments with isolated gp71 in mice. The induced immunity was highly specific and not operative against endogenous murine C-viruses belonging to other serotypes. Surprisingly the latter were found to be activated by the vaccination with gp71 of FLV. In heterologous animal species isolated FLV-gp71 induced the formation of broadly reacting antibodies. They were found to be effective in the therapy of infections with FLV in mice as well as with feline leukaemia virus in cats. Most impressive results were obtained with an antiserum prepared against feline leukaemia virus in a goat. This serum completely suppressed sarcomas induced by infection with feline sarcoma virus."}
{"id": "PMID:198603", "title": "[Factors involved in the development of human tumors using the Epstein-Barr virus as an example (author's transl)].", "content": "Several viruses induce tumors in animals under experimental or natural conditions. It is likely therefore that some human malignancies are also caused by viruses. Proof of this hypothesis can be provided only by indirect evidence based on the following criteria: (1) detection of viral antigens or viral genetic information in a given tumor; (2) transformation of normal human cells by the virus in tissue culture; (3) induction of tumors in animals by the virus; and (4) demonstration of enhanced titers of antibodies to the virus in patients bearing the tumor. These criteria have been fulfilled to support a causal relationship of the Epstein-Barr virus (EBV) in Burkitt's lymphoma and nasopharyngeal carcinoma. It is clear, however, that factors of a genetic, immunologic or environmental nature must play an additional role because EBV, the cause of infectious mononucleosis, is widely disseminated yet development of the tumors is a rare event.", "contents": "[Factors involved in the development of human tumors using the Epstein-Barr virus as an example (author's transl)]. Several viruses induce tumors in animals under experimental or natural conditions. It is likely therefore that some human malignancies are also caused by viruses. Proof of this hypothesis can be provided only by indirect evidence based on the following criteria: (1) detection of viral antigens or viral genetic information in a given tumor; (2) transformation of normal human cells by the virus in tissue culture; (3) induction of tumors in animals by the virus; and (4) demonstration of enhanced titers of antibodies to the virus in patients bearing the tumor. These criteria have been fulfilled to support a causal relationship of the Epstein-Barr virus (EBV) in Burkitt's lymphoma and nasopharyngeal carcinoma. It is clear, however, that factors of a genetic, immunologic or environmental nature must play an additional role because EBV, the cause of infectious mononucleosis, is widely disseminated yet development of the tumors is a rare event."}
{"id": "PMID:198606", "title": "The gastrin-producing cells in tissue cultures of the rat pyloric antrum.", "content": "Tissue culture methods were used to study the gastrin-producing cells isolated from the pyloric antral mucosa of rats. Cultures were maintained for up to 7 days. Gastrin cells were identified by means of immunofluorescent and unlabeled antibody-enzyme techniques. The tissue culture medium was monitored for basal gastrin secretion. In addition, stimulation of gastrin release was achieved by the use of dibutyryl cyclic-AMP and theophylline. This is the first report of the successful application of tissue culture methods to the functional study of antral gastrin cells. The procedure has proven to be useful in assessing the mechanisms of gastrin secretion.", "contents": "The gastrin-producing cells in tissue cultures of the rat pyloric antrum. Tissue culture methods were used to study the gastrin-producing cells isolated from the pyloric antral mucosa of rats. Cultures were maintained for up to 7 days. Gastrin cells were identified by means of immunofluorescent and unlabeled antibody-enzyme techniques. The tissue culture medium was monitored for basal gastrin secretion. In addition, stimulation of gastrin release was achieved by the use of dibutyryl cyclic-AMP and theophylline. This is the first report of the successful application of tissue culture methods to the functional study of antral gastrin cells. The procedure has proven to be useful in assessing the mechanisms of gastrin secretion."}
{"id": "PMID:198608", "title": "The place of electrical stimulation in the physiotherapy of leprosy.", "content": "The production of nerve and muscle impulses by faradic and interrupted direct current, and the \"Strength-duration curves\" plotted for normal, denervated, and partially denervated muscles, are described. The advantages and disadvantages of such electrical stimulation in the testing of recent paralysis, the treatment of recent paralysis, and following tendon transfer surgery, in leprosy patients, are discussed. In the light of these, electrical stimulation is concluded to have only a minor role in the Physiotherapy of leprosy.", "contents": "The place of electrical stimulation in the physiotherapy of leprosy. The production of nerve and muscle impulses by faradic and interrupted direct current, and the \"Strength-duration curves\" plotted for normal, denervated, and partially denervated muscles, are described. The advantages and disadvantages of such electrical stimulation in the testing of recent paralysis, the treatment of recent paralysis, and following tendon transfer surgery, in leprosy patients, are discussed. In the light of these, electrical stimulation is concluded to have only a minor role in the Physiotherapy of leprosy."}
{"id": "PMID:198609", "title": "Pattern of reactions in leprosy: a clinical appraisal.", "content": "The term 'reactions' is applied in the present text, to describe the acute episodes, recognized with the different types of leprosy. The incidence of reactions was found to be 9.7% of 1053 cases examined. They were seen in all types of leprosy, but their frequency and severity was marked in lepromatous and borderline cases, and in majority of them, the age ranged from 20-40 years. The precipitating factor(s) could not be established in many; in some dapsone was incriminated, followed by bacterial infection and malnutrition. The exacerbations of the existing lesion(s) either alone or in combination with new lesions (E.N.L.) and E.N.L. lesions alone, were the presenting clinical features. The constitutional symptoms were observed largely in the types other than the tuberculoid. Foot drop and contractures of the fingers were the common sequels of the reactions. An attempt has been made to explain their mechanisms in the light of the recent literature.", "contents": "Pattern of reactions in leprosy: a clinical appraisal. The term 'reactions' is applied in the present text, to describe the acute episodes, recognized with the different types of leprosy. The incidence of reactions was found to be 9.7% of 1053 cases examined. They were seen in all types of leprosy, but their frequency and severity was marked in lepromatous and borderline cases, and in majority of them, the age ranged from 20-40 years. The precipitating factor(s) could not be established in many; in some dapsone was incriminated, followed by bacterial infection and malnutrition. The exacerbations of the existing lesion(s) either alone or in combination with new lesions (E.N.L.) and E.N.L. lesions alone, were the presenting clinical features. The constitutional symptoms were observed largely in the types other than the tuberculoid. Foot drop and contractures of the fingers were the common sequels of the reactions. An attempt has been made to explain their mechanisms in the light of the recent literature."}
{"id": "PMID:198613", "title": "Hormonal regulation of hepatic amino acid transport.", "content": "The transport of 2-aminoisobutyric acid (AIB) into liver tissue was increased by both insulin and glucagon. We have now shown that these hormones do not stimulate the same transport system. Glucagon, possibly via cAMP, increased the hepatic uptake of AIB by a mechanism which resembled system A. This glucagon-sensitive system could be monitored by the use of the model amino acid MeAIB. In contrast, the insulin-stimulated system exhibited little or no affinity for MeAIB and will be referred to as system B. On the basis of other reports that the hepatic transport of AIB is almost entirely Na+ dependent and the present finding that the uptake of 2-aminobicyclo [2,2]heptane-2-carboxylic acid (BCH) was not stimulated by either hormone, we conclude that system B is Na+ dependent. Furthermore, insulin added to the perfusate of livers from glucagon-pretreated donors suppressed the increase in AIB or MeAIB uptake. Depending upon the specificities of systems A and B, both of which are unknown for liver tissue, the insulin/glucagon ratio may alter the composition of the intracellular pool of amino acids.", "contents": "Hormonal regulation of hepatic amino acid transport. The transport of 2-aminoisobutyric acid (AIB) into liver tissue was increased by both insulin and glucagon. We have now shown that these hormones do not stimulate the same transport system. Glucagon, possibly via cAMP, increased the hepatic uptake of AIB by a mechanism which resembled system A. This glucagon-sensitive system could be monitored by the use of the model amino acid MeAIB. In contrast, the insulin-stimulated system exhibited little or no affinity for MeAIB and will be referred to as system B. On the basis of other reports that the hepatic transport of AIB is almost entirely Na+ dependent and the present finding that the uptake of 2-aminobicyclo [2,2]heptane-2-carboxylic acid (BCH) was not stimulated by either hormone, we conclude that system B is Na+ dependent. Furthermore, insulin added to the perfusate of livers from glucagon-pretreated donors suppressed the increase in AIB or MeAIB uptake. Depending upon the specificities of systems A and B, both of which are unknown for liver tissue, the insulin/glucagon ratio may alter the composition of the intracellular pool of amino acids."}
{"id": "PMID:198614", "title": "Perspectives and limitations of resolutions-reconstitution experiments.", "content": "Reconstitutions of membranous activities can tell us how many components are required and what their functions are. The mitochondrial proton pump is used as an example. Moreover, the biological activity, such as Pi transport, can be used in reconstituted vesicles as an assay during the isolation of the transporter. Reconstitution experiments reveal the importance of membrane asymmetry and allow us to study conditions of vectorial assembly. The mechanism of action of ion pumps has been successfully analyzed in reconstituted liposomes. We can study the movement of ions and the electrogenicity of the system without interference by other unrelated processes. Based on studies with the resolved Ca2+-ATPase of sarcoplasmic reticulum, we propose a novel formulation of the mechanism of ATP-driven ion pumps in which cyclic binding of Mg2+ plays a key role.", "contents": "Perspectives and limitations of resolutions-reconstitution experiments. Reconstitutions of membranous activities can tell us how many components are required and what their functions are. The mitochondrial proton pump is used as an example. Moreover, the biological activity, such as Pi transport, can be used in reconstituted vesicles as an assay during the isolation of the transporter. Reconstitution experiments reveal the importance of membrane asymmetry and allow us to study conditions of vectorial assembly. The mechanism of action of ion pumps has been successfully analyzed in reconstituted liposomes. We can study the movement of ions and the electrogenicity of the system without interference by other unrelated processes. Based on studies with the resolved Ca2+-ATPase of sarcoplasmic reticulum, we propose a novel formulation of the mechanism of ATP-driven ion pumps in which cyclic binding of Mg2+ plays a key role."}
{"id": "PMID:198619", "title": "[Granular cell tumour of the parotid gland. The differential diagnostic criteria (author's transl)].", "content": "Granular cell tumours (synonyms: myoblastmyomas, granular neuromas, granular cell myoblastomas) are localized predominantly in the head and neck area, especially in the region of tongue and larynx. Only 2 observations of an occurrence in the parotid gland exist till now in the world literature. This paper reports a further case of an occurrence in the parotid gland in a 6-years-old girl. The about cherrygreat tumour was distinctly limited and showed histologically a typic lobular arrangement of acidophilic granular cells. No recidive was observed in the prevailing postoperative phase of 3 years. The differential diagnosis of the granular cell tumorus is demonstrated to other tumour types with similar histological arrangement, expecially to the alveolar soft-part sarcoma, the acinic cell tumour and the non-chrom-affine paraganglioma (chemodectoma).", "contents": "[Granular cell tumour of the parotid gland. The differential diagnostic criteria (author's transl)]. Granular cell tumours (synonyms: myoblastmyomas, granular neuromas, granular cell myoblastomas) are localized predominantly in the head and neck area, especially in the region of tongue and larynx. Only 2 observations of an occurrence in the parotid gland exist till now in the world literature. This paper reports a further case of an occurrence in the parotid gland in a 6-years-old girl. The about cherrygreat tumour was distinctly limited and showed histologically a typic lobular arrangement of acidophilic granular cells. No recidive was observed in the prevailing postoperative phase of 3 years. The differential diagnosis of the granular cell tumorus is demonstrated to other tumour types with similar histological arrangement, expecially to the alveolar soft-part sarcoma, the acinic cell tumour and the non-chrom-affine paraganglioma (chemodectoma)."}
{"id": "PMID:198635", "title": "Antigenic variation of poliovirus caused by antibody components with different specificities.", "content": "The possible role of antibody as a selective pressure on antigenic mutants of poliovirus in nature was investigated in vitro. A mutant resistant to a monospecific antibody with a definite specificity was readily obtained by several cycles of neutralization of Mahoney strain with a monospecific antibody and multiplication in monkey kidney (MS) cells. Mutants resistant to more than two different monospecific antibodies were also readily obtained in a similar manner. Studies on the antigenicity of these mutants by kinetic neutralization tests revealed that the Mahoney strain underwent a progressive serological variation as it became successively resistant to one to five different monospecific antibodies isolated from anti-Mahoney serum.", "contents": "Antigenic variation of poliovirus caused by antibody components with different specificities. The possible role of antibody as a selective pressure on antigenic mutants of poliovirus in nature was investigated in vitro. A mutant resistant to a monospecific antibody with a definite specificity was readily obtained by several cycles of neutralization of Mahoney strain with a monospecific antibody and multiplication in monkey kidney (MS) cells. Mutants resistant to more than two different monospecific antibodies were also readily obtained in a similar manner. Studies on the antigenicity of these mutants by kinetic neutralization tests revealed that the Mahoney strain underwent a progressive serological variation as it became successively resistant to one to five different monospecific antibodies isolated from anti-Mahoney serum."}
{"id": "PMID:198639", "title": "Restitution of hemagglutinating activity to spikeless particles of HVJ (Sendai virus) by glycoprotein components of Newcastle disease virus.", "content": "Spikeless particles of HVJ (Sendai virus) lacking in hemagglutinating (HA) activity were obtained by enzymatic digestion of virions with trypsin followed by centrifugation through a sucrose gradient. When they were mixed with glycoprotein components of Newcastle disease virus (NDV) obtained by treatment of purified virions with deoxycholate (DOC), the mixture showed hemagglutination reaction, which was inhibited by anti-NDV serum, but not by anti-HVJ serum. Sedimentation profile of the HA active agents was then examined by centrifugation of the mixture of spikeless particles of HVJ (labeled with 3H-uridine) and glycoproteins of NDV (labeled with 14C-amino acid mixture). The results showed that the peak of HA activity had both of the radioactivities, and that the sedimentation rate of the HA was faster than that of spikeless HVJ but slower than that of intact HVJ. Electron micrographs of such HA active structures showed that they were morphologically closely similar to intact virion of HVJ, although they had neither hemolytic activity nor infectivity. The mixture of spikeless HVJ and glycoproteins of HVJ or NDV which were removed from virions by proteolytic enzymes, on the other hand, did not show any detectable hemagglutinating activity.", "contents": "Restitution of hemagglutinating activity to spikeless particles of HVJ (Sendai virus) by glycoprotein components of Newcastle disease virus. Spikeless particles of HVJ (Sendai virus) lacking in hemagglutinating (HA) activity were obtained by enzymatic digestion of virions with trypsin followed by centrifugation through a sucrose gradient. When they were mixed with glycoprotein components of Newcastle disease virus (NDV) obtained by treatment of purified virions with deoxycholate (DOC), the mixture showed hemagglutination reaction, which was inhibited by anti-NDV serum, but not by anti-HVJ serum. Sedimentation profile of the HA active agents was then examined by centrifugation of the mixture of spikeless particles of HVJ (labeled with 3H-uridine) and glycoproteins of NDV (labeled with 14C-amino acid mixture). The results showed that the peak of HA activity had both of the radioactivities, and that the sedimentation rate of the HA was faster than that of spikeless HVJ but slower than that of intact HVJ. Electron micrographs of such HA active structures showed that they were morphologically closely similar to intact virion of HVJ, although they had neither hemolytic activity nor infectivity. The mixture of spikeless HVJ and glycoproteins of HVJ or NDV which were removed from virions by proteolytic enzymes, on the other hand, did not show any detectable hemagglutinating activity."}
{"id": "PMID:198640", "title": "[Respiratory chain of Candida mycoderma].", "content": "The respiration chain of the yeast Candida mycoderma was studied during its growth on glucose. Electrons can be transported from the pyridine nucleotide (PN) pool to oxygen by two pathways, as was shown in experiments with intact cells on the basis of inhibitory analysis of respiration and the extent of reduction of electron carriers. The first pathway is inhibited by cyanide and antimycin A; it includes PN, flavoprotein, (FP) and cytochromes b, c and a + a3. The second pathway of electron transport is resistant to cyanide (CrPET), includes PN and FP, lacks cytochromes, and is blocked by salicyl- or benzhydroxamic acid. Two flavoprotein NADH-dehydrogenases are present in the cells of C. mycoderma: one is sensitive to rotenone, the other is resistant to it. The terminal electron acceptor can be not only O2, but also H2O2; in the latter case, electron transport involves PN, FP, and cytochromes b and c. At the exponential growth phase, only the first pathway of electron transport, including rotenone-resistant NADH-dehydrogenase, functions. At the phase when the rate of growth decreased, both pathways of electron transport and the two dehydrogenases are involved. At the stationary phase, mainly CrPET functions, but both NADH-dehydrogenases participate.", "contents": "[Respiratory chain of Candida mycoderma]. The respiration chain of the yeast Candida mycoderma was studied during its growth on glucose. Electrons can be transported from the pyridine nucleotide (PN) pool to oxygen by two pathways, as was shown in experiments with intact cells on the basis of inhibitory analysis of respiration and the extent of reduction of electron carriers. The first pathway is inhibited by cyanide and antimycin A; it includes PN, flavoprotein, (FP) and cytochromes b, c and a + a3. The second pathway of electron transport is resistant to cyanide (CrPET), includes PN and FP, lacks cytochromes, and is blocked by salicyl- or benzhydroxamic acid. Two flavoprotein NADH-dehydrogenases are present in the cells of C. mycoderma: one is sensitive to rotenone, the other is resistant to it. The terminal electron acceptor can be not only O2, but also H2O2; in the latter case, electron transport involves PN, FP, and cytochromes b and c. At the exponential growth phase, only the first pathway of electron transport, including rotenone-resistant NADH-dehydrogenase, functions. At the phase when the rate of growth decreased, both pathways of electron transport and the two dehydrogenases are involved. At the stationary phase, mainly CrPET functions, but both NADH-dehydrogenases participate."}
{"id": "PMID:198648", "title": "Microassay with the NADH-induced light reaction, technique improved by means of purified enzymes from Achromobacter fischeri.", "content": "Purification of a commercial preparation of Achromobacter fischeri was carried out by agarose-suspension electrophoresis and by molecular-sieve chromatography. Both the luciferase and an oxidoreductase, catalyzing reduction of FMN with NADH, were obtained in more than one form. Flavins, liable to interfere with the light production in analytical applications, were present in amounts worthy of consideration, but seem to be firmly bound to protein. The major quantity was found in the enzymatically inactive fractions. In free zone electrophoresis of the main luciferase component, the mobility of the zone containing enzyme activity was calculated to -4.0 X 10(-5) cm2 sec-1 V-1 at 12 degrees C. Fractions of the two enzymes were separated and mixed in different proportions to study how the intensity and time course of NADH-induced light emission can be modified. These experiments disclosed how reaction mixtures will have to be composed in appropriate photokinetic assays, using NADH as measurable product. A regenerating system based on the purified fractions is described. Instead of the light flash, following the consumption of NADH, the light is emitted on a well maintained level, permitting assays with a less elaborate equipment than the one required for the recording of fast reactions.", "contents": "Microassay with the NADH-induced light reaction, technique improved by means of purified enzymes from Achromobacter fischeri. Purification of a commercial preparation of Achromobacter fischeri was carried out by agarose-suspension electrophoresis and by molecular-sieve chromatography. Both the luciferase and an oxidoreductase, catalyzing reduction of FMN with NADH, were obtained in more than one form. Flavins, liable to interfere with the light production in analytical applications, were present in amounts worthy of consideration, but seem to be firmly bound to protein. The major quantity was found in the enzymatically inactive fractions. In free zone electrophoresis of the main luciferase component, the mobility of the zone containing enzyme activity was calculated to -4.0 X 10(-5) cm2 sec-1 V-1 at 12 degrees C. Fractions of the two enzymes were separated and mixed in different proportions to study how the intensity and time course of NADH-induced light emission can be modified. These experiments disclosed how reaction mixtures will have to be composed in appropriate photokinetic assays, using NADH as measurable product. A regenerating system based on the purified fractions is described. Instead of the light flash, following the consumption of NADH, the light is emitted on a well maintained level, permitting assays with a less elaborate equipment than the one required for the recording of fast reactions."}
{"id": "PMID:198649", "title": "[Functional anatomy of low back pain and ischialgia (author's transl)].", "content": "The neuronal systems involved in low back pain are first described in a functional anatomical review and then an attempt is made to work out the special functional structure data which seem to be decisive for the origin and localization of low back pain and ischialgia. Low back pain may arise as a deep pain through stimulation of the nociceptive afferents in the musculature and supporting tissues and as a neural pain through irritation of nociceptive nerve fibers within the innervation area of the lumbosacral plexus. The nociceptive influx from the viscera only elicits pain in the rarest cases, however, it often has a conductive influence. Skeletal muscle plays a special role here, along with the sensory supply to the vertebral motor segment through the spinal nerve and the particular innervation scheme of the lumbosacral plexus caused by the limb budding.", "contents": "[Functional anatomy of low back pain and ischialgia (author's transl)]. The neuronal systems involved in low back pain are first described in a functional anatomical review and then an attempt is made to work out the special functional structure data which seem to be decisive for the origin and localization of low back pain and ischialgia. Low back pain may arise as a deep pain through stimulation of the nociceptive afferents in the musculature and supporting tissues and as a neural pain through irritation of nociceptive nerve fibers within the innervation area of the lumbosacral plexus. The nociceptive influx from the viscera only elicits pain in the rarest cases, however, it often has a conductive influence. Skeletal muscle plays a special role here, along with the sensory supply to the vertebral motor segment through the spinal nerve and the particular innervation scheme of the lumbosacral plexus caused by the limb budding."}
{"id": "PMID:198650", "title": "[Neurological aspects of the differential diagnosis of low back pain (author's transl)].", "content": "The close relationships between the bony spinal column, spinal marrow and the emerging nerve roots explain the frequency of neurological symptoms of diseases in the region of the lumbar vertebrae, the sacrum and the pelvis. After a short description of the local diagnostic signs in lumbosacral pains, further important differential diagnostic aspects of the changes in the vertebral column besides those of the intervertebral disks, inflammatory changes in the vertebrae, intramedullary tumors as well as a few rare pain syndromes in peripheral nerve diseases are discussed.", "contents": "[Neurological aspects of the differential diagnosis of low back pain (author's transl)]. The close relationships between the bony spinal column, spinal marrow and the emerging nerve roots explain the frequency of neurological symptoms of diseases in the region of the lumbar vertebrae, the sacrum and the pelvis. After a short description of the local diagnostic signs in lumbosacral pains, further important differential diagnostic aspects of the changes in the vertebral column besides those of the intervertebral disks, inflammatory changes in the vertebrae, intramedullary tumors as well as a few rare pain syndromes in peripheral nerve diseases are discussed."}
{"id": "PMID:198651", "title": "[The role of cyclic AMP in the control of insulin secretion (author's transl)].", "content": "D-glucose stimulates the accumulation of cyclic AMP in isolated islets of Langerhans in a dose-dependent manner. This effect is present as long as the sugar remains elevated in the incubate. Under present experimental conditions the stimulation of cyclic AMP precedes insulin release. Islet or medium cyclic AMP, and insulin secretion are closely correlated at various incubation times. We conclude that the beta-cell cyclic AMP system is one of the major mediators of the glucose signal to insulin secretion. Tolbutamide and glibenclamide have similar effects in the absence or with low concentrations of glucose. These results may indicate that these sulfonylurea derivates act at sites where glucose exerts its effect.", "contents": "[The role of cyclic AMP in the control of insulin secretion (author's transl)]. D-glucose stimulates the accumulation of cyclic AMP in isolated islets of Langerhans in a dose-dependent manner. This effect is present as long as the sugar remains elevated in the incubate. Under present experimental conditions the stimulation of cyclic AMP precedes insulin release. Islet or medium cyclic AMP, and insulin secretion are closely correlated at various incubation times. We conclude that the beta-cell cyclic AMP system is one of the major mediators of the glucose signal to insulin secretion. Tolbutamide and glibenclamide have similar effects in the absence or with low concentrations of glucose. These results may indicate that these sulfonylurea derivates act at sites where glucose exerts its effect."}
{"id": "PMID:198652", "title": "Decline in mutation frequency in temperature-sensitive SV40 viruses before viral DNA synthesis.", "content": "Lesions that promote reversion from a temperature-sensitive to a wild-type phenotype were induced in temperature-sensitive late mutants of SV40 virus by UV irradiation. When cultures infected with UV-irradiated temperature-sensitive mutants were grown for various times at permissive temperature (35 degrees C) and then at restrictive temperature (39 degrees C), the reversion frequency declined just before the onset of semiconservative DNA synthesis when DNA synthesis began at 32 degrees C. This can be explained by competition between reactions that lead to the onset of viral DNA synthesis and reactions that repair the lesions before the onset of viral DNA synthesis.", "contents": "Decline in mutation frequency in temperature-sensitive SV40 viruses before viral DNA synthesis. Lesions that promote reversion from a temperature-sensitive to a wild-type phenotype were induced in temperature-sensitive late mutants of SV40 virus by UV irradiation. When cultures infected with UV-irradiated temperature-sensitive mutants were grown for various times at permissive temperature (35 degrees C) and then at restrictive temperature (39 degrees C), the reversion frequency declined just before the onset of semiconservative DNA synthesis when DNA synthesis began at 32 degrees C. This can be explained by competition between reactions that lead to the onset of viral DNA synthesis and reactions that repair the lesions before the onset of viral DNA synthesis."}
{"id": "PMID:198654", "title": "Paradoxical ACTH response to glucocorticoids in Cushing's disease.", "content": "To define further the defect in the steroid feedback mechanism in Cushing's disease, we studied the acute effects of intravenous administration of glucorticoids on plasma ACTH levels in seven patients with this disease after total adrenalectomy. In seven other patients with hypoadrenocorticism ACTH was readily suppressed; a significant decrease (72.5+/-5 per cent, mean +/- S.E.M., P less than 0.002) occurred within 15 minutes of the start of an infusion of 50 mg per hour of cortisol. In contrast, in the seven adrenalectomized patients with Cushing's disease, cortisol induced a transient paradoxical rise in ACTH levels, with a maximum at 15 minutes (347+/-99 per cent,, P less than 0.05). A similar ACTH response was observed with dexamethasone. Cushing's disease is characterized by a paradoxical transient rise in ACTH after glucocorticoid administration. This effect was more pronounced in adrenalectomized than in nonadrenalectomized patients.", "contents": "Paradoxical ACTH response to glucocorticoids in Cushing's disease. To define further the defect in the steroid feedback mechanism in Cushing's disease, we studied the acute effects of intravenous administration of glucorticoids on plasma ACTH levels in seven patients with this disease after total adrenalectomy. In seven other patients with hypoadrenocorticism ACTH was readily suppressed; a significant decrease (72.5+/-5 per cent, mean +/- S.E.M., P less than 0.002) occurred within 15 minutes of the start of an infusion of 50 mg per hour of cortisol. In contrast, in the seven adrenalectomized patients with Cushing's disease, cortisol induced a transient paradoxical rise in ACTH levels, with a maximum at 15 minutes (347+/-99 per cent,, P less than 0.05). A similar ACTH response was observed with dexamethasone. Cushing's disease is characterized by a paradoxical transient rise in ACTH after glucocorticoid administration. This effect was more pronounced in adrenalectomized than in nonadrenalectomized patients."}
{"id": "PMID:198659", "title": "Factitious hypoglycemia. Diagnosis by measurement of serum C-peptide immunoreactivity and insulin-binding antibodies.", "content": "In seven patients with factitious hypoglycemia due to the surreptitious injection of insulin, we made the diagnosis by measurements of plasma insulin and C-peptide immunoreactivity (in seven patients), facilitated by the finding of circulating insulin-binding antibodies (in two patients). The simultaneous demonstration of low plasma glucose, high immunoreactive insulin and suppressed C-peptide immunoreactivity represents a triad of results pathognomonic of exogenous insulin administration. Determination of plasma free C-peptide and free insulin permitted patients with high titers of insulin antibodies, including those with a history of insulin-treated diabetes, to be studied and diagnosed in a way similar to that in subjects who had no circulating insulin antibodies.", "contents": "Factitious hypoglycemia. Diagnosis by measurement of serum C-peptide immunoreactivity and insulin-binding antibodies. In seven patients with factitious hypoglycemia due to the surreptitious injection of insulin, we made the diagnosis by measurements of plasma insulin and C-peptide immunoreactivity (in seven patients), facilitated by the finding of circulating insulin-binding antibodies (in two patients). The simultaneous demonstration of low plasma glucose, high immunoreactive insulin and suppressed C-peptide immunoreactivity represents a triad of results pathognomonic of exogenous insulin administration. Determination of plasma free C-peptide and free insulin permitted patients with high titers of insulin antibodies, including those with a history of insulin-treated diabetes, to be studied and diagnosed in a way similar to that in subjects who had no circulating insulin antibodies."}
{"id": "PMID:198660", "title": "Variable phenotypic expression of an X-linked recessive lymphoproliferative syndrome.", "content": "Investigation of a family with cancer in boys revealed that at least 20 males had the X-linked recessive lymphoproliferative syndrome. A variety of phenotypes occurred: aproliferative phenotypes consisted of aplastic anemia, agranulocytosis or acquired hypogammaglobulinemia; and proliferative phenotypes of B cells included disorders associated with the Epstein-Barr virus, American Burkitt's lymphoma, immunoblastic sarcoma of B cells, fatal infectious mononucleosis or plasmacytoma. The lymphoproliferative disorders observed in males could have resulted from an immunodeficiency to Epstein-Barr virus. The variable phenotypic expression could have resulted from individual differences in the viral dose, duration of exposure and age at which the boys were exposed to the virus. Aproliferative phenotypes such as acquired hypogammaglobulinemia could have ensued from excessive suppressor-cell activity on B cells, whereas proliferative phenotypes such as Burkitt's lymphoma or fatal infectious mononucleosis could have resulted from infection by Epstein-Barr virus and failure to stop proliferation of B cells.", "contents": "Variable phenotypic expression of an X-linked recessive lymphoproliferative syndrome. Investigation of a family with cancer in boys revealed that at least 20 males had the X-linked recessive lymphoproliferative syndrome. A variety of phenotypes occurred: aproliferative phenotypes consisted of aplastic anemia, agranulocytosis or acquired hypogammaglobulinemia; and proliferative phenotypes of B cells included disorders associated with the Epstein-Barr virus, American Burkitt's lymphoma, immunoblastic sarcoma of B cells, fatal infectious mononucleosis or plasmacytoma. The lymphoproliferative disorders observed in males could have resulted from an immunodeficiency to Epstein-Barr virus. The variable phenotypic expression could have resulted from individual differences in the viral dose, duration of exposure and age at which the boys were exposed to the virus. Aproliferative phenotypes such as acquired hypogammaglobulinemia could have ensued from excessive suppressor-cell activity on B cells, whereas proliferative phenotypes such as Burkitt's lymphoma or fatal infectious mononucleosis could have resulted from infection by Epstein-Barr virus and failure to stop proliferation of B cells."}
{"id": "PMID:198661", "title": "Selective deficiency of 1,25-dihydroxycholecalciferol. A cause of isolated skeletal resistance to parathyroid hormone.", "content": "To investigate the role of vitamin D metabolites in the pathogenesis of pseudohypoparathyroidism, we studied an elderly man with a unique variant of the disease, which was characterized by hypocalcemia, elevated serum parathyroid hormone (513 +/- 13 pg per milliliter, mean +/- S.E.M., normal, less than 450) but normal renal responses (phosphate and cyclic AMP) to exogenous parathyroid extract. Treatment with parathyroid extract did not produce a calcemic effect, suggesting an isolated skeletal hyporesponsiveness to parathyroid hormone. Although 25-hydroxyvitamin D levels were not reduced, levels of 1,25-dihydroxycholecalciferol were extremely low (0.52 ng per deciliter; normal 3.3 +/- 0.06, S.D.). Treatment with 1,25-dihydroxycholecalciferol (1 microgram by mouth per day for four days) increased circulating levels to normal (4.60 ng per deciliter) and restored to normal the calcemic response to parathyroid (change in calcium 3.0 mg per deciliter). These data suggest that 1,25-dihydroxycholecalciferol deficiency may explain the skeletal resistance, but not the renal resistance, often present in classic pseudohypoparathyroidism.", "contents": "Selective deficiency of 1,25-dihydroxycholecalciferol. A cause of isolated skeletal resistance to parathyroid hormone. To investigate the role of vitamin D metabolites in the pathogenesis of pseudohypoparathyroidism, we studied an elderly man with a unique variant of the disease, which was characterized by hypocalcemia, elevated serum parathyroid hormone (513 +/- 13 pg per milliliter, mean +/- S.E.M., normal, less than 450) but normal renal responses (phosphate and cyclic AMP) to exogenous parathyroid extract. Treatment with parathyroid extract did not produce a calcemic effect, suggesting an isolated skeletal hyporesponsiveness to parathyroid hormone. Although 25-hydroxyvitamin D levels were not reduced, levels of 1,25-dihydroxycholecalciferol were extremely low (0.52 ng per deciliter; normal 3.3 +/- 0.06, S.D.). Treatment with 1,25-dihydroxycholecalciferol (1 microgram by mouth per day for four days) increased circulating levels to normal (4.60 ng per deciliter) and restored to normal the calcemic response to parathyroid (change in calcium 3.0 mg per deciliter). These data suggest that 1,25-dihydroxycholecalciferol deficiency may explain the skeletal resistance, but not the renal resistance, often present in classic pseudohypoparathyroidism."}
{"id": "PMID:198678", "title": "Iontrophoretic application of autonomic mediators and cyclic nucleotides in the sinus node cells.", "content": "The effects of intracellular application of noradrenaline, acetylcholine, cAMP and cGMP were studied in the sinus-node of the rabbit. Noradrenaline and acetylcholine were without effect on electrical activity. In about one third of cases, cAMP increased, and cGMP decreased the slope of slow depolarization. These results suggest that adrenergic as well as cholinergic receptors which control the electrical activity of the sinus node cell are localized at the outer side of the cell membrane. It has also been shown that the cyclic nucleotides exert direct but opposite chronotropic effects.", "contents": "Iontrophoretic application of autonomic mediators and cyclic nucleotides in the sinus node cells. The effects of intracellular application of noradrenaline, acetylcholine, cAMP and cGMP were studied in the sinus-node of the rabbit. Noradrenaline and acetylcholine were without effect on electrical activity. In about one third of cases, cAMP increased, and cGMP decreased the slope of slow depolarization. These results suggest that adrenergic as well as cholinergic receptors which control the electrical activity of the sinus node cell are localized at the outer side of the cell membrane. It has also been shown that the cyclic nucleotides exert direct but opposite chronotropic effects."}
{"id": "PMID:198679", "title": "alpha-Adrenoceptor-mediated inhibitory effect of the sympathetic nervous system on the isoprenaline-induced increase in plasma renin concentration.", "content": "The importance of the sympatho-adrenal system for the isoprenaline-induced increase in plasma renin concentration was investigated in conscious rats Ganglionic blockade by trimethidinium (10 mg kg-1) increased the dose-dependent elevation of plasma renin concentration induced by isoprenaline (0.03-0.48 microgram kg-1 min-1). Also treatment of the rats with guanethidine (6 mg kg-1) or reserpine (2.5 mg kg-1, given 16 and 7 h prior to the experiments) further increased the effect of isoprenaline (0.5 microgram kg-1 min-1) on plasma renin concentration. Unilateral renal denervation combined with contralateral nephrectomy doubled the effect of the beta-sympathomimetic amine on renin release. The alpha-adrenoceptor antagonist phenoxy-benzamine (3 mg kg-1) also enhanced the effect of isoprenaline on this parameter. It is concluded that apart from a stimulation of renin release via beta-adrenoceptors the sympathetic nervous system may inhibit renin release via stimulation of alpha-adrenoceptors.", "contents": "alpha-Adrenoceptor-mediated inhibitory effect of the sympathetic nervous system on the isoprenaline-induced increase in plasma renin concentration. The importance of the sympatho-adrenal system for the isoprenaline-induced increase in plasma renin concentration was investigated in conscious rats Ganglionic blockade by trimethidinium (10 mg kg-1) increased the dose-dependent elevation of plasma renin concentration induced by isoprenaline (0.03-0.48 microgram kg-1 min-1). Also treatment of the rats with guanethidine (6 mg kg-1) or reserpine (2.5 mg kg-1, given 16 and 7 h prior to the experiments) further increased the effect of isoprenaline (0.5 microgram kg-1 min-1) on plasma renin concentration. Unilateral renal denervation combined with contralateral nephrectomy doubled the effect of the beta-sympathomimetic amine on renin release. The alpha-adrenoceptor antagonist phenoxy-benzamine (3 mg kg-1) also enhanced the effect of isoprenaline on this parameter. It is concluded that apart from a stimulation of renin release via beta-adrenoceptors the sympathetic nervous system may inhibit renin release via stimulation of alpha-adrenoceptors."}
{"id": "PMID:198683", "title": "Effects of Sr2+ and Mg2+ on the phospholipase A and the presynaptic neuromuscular blocking actions of beta-bungarotoxin, crotoxin and taipoxin.", "content": "1.beta-Bungarotoxin, crotoxin and taipoxin, presynaptic neurotoxins of snake venom origin, have about the same phospholipid-splitting activities as a much less toxic cobra phospholipase A2 in the presence of Ca2+ and deoxycholate. 2. Sr2+ was a much less effective activator of the enzymes than is Ca2+, the activation by Sr2+ being only 3-6% for beta-bungarotoxin and crotoxin and 12% for taipoxin. 3. Sr2+ also inhibited the Ca2+ -activated enzymes by 80% in the cases of beta-bungarotoxin and crotoxin, but only 16% in the case of taipoxin. 4. Mg2\" had no significant effect on beta-bungarotoxin or crotoxin, but activated taipoxin in the presence or absence of Ca2\". 5. In Sr2+ -Tyrode lacking Ca2+ all three toxins exhibited the same immediate depression followed by facilitation in the rat and mouse diaphragms, but the final blocking activity was only 3-10% with beta-bungarotoxin and crotoxin and was 30% with taipoxin. 6. In Sr2+ -Tyrode, increasing in the rate of nerve stimulation had less accelerating effect on the development of neuromuscular block than in Ca2+ -Tyrode for any of the toxins. 7. Removal of Mg2+ from Sr2+ -Tyrode did not diminish the potency of taipoxin in blocking neuromuscular transmission, suggesting that enzyme activity at the outer surface of the axolemma does not contribute to the neuromuscular blocking action. 8. All of the results indicate that there are close correlations between the presynaptic activities of these toxins and their phospholipid-splitting activities in the cationic environment prevailing in the axoplasm. Apparently the final blocking effect of these toxins is due to phospholipase A action within the nerve terminal.", "contents": "Effects of Sr2+ and Mg2+ on the phospholipase A and the presynaptic neuromuscular blocking actions of beta-bungarotoxin, crotoxin and taipoxin. 1.beta-Bungarotoxin, crotoxin and taipoxin, presynaptic neurotoxins of snake venom origin, have about the same phospholipid-splitting activities as a much less toxic cobra phospholipase A2 in the presence of Ca2+ and deoxycholate. 2. Sr2+ was a much less effective activator of the enzymes than is Ca2+, the activation by Sr2+ being only 3-6% for beta-bungarotoxin and crotoxin and 12% for taipoxin. 3. Sr2+ also inhibited the Ca2+ -activated enzymes by 80% in the cases of beta-bungarotoxin and crotoxin, but only 16% in the case of taipoxin. 4. Mg2\" had no significant effect on beta-bungarotoxin or crotoxin, but activated taipoxin in the presence or absence of Ca2\". 5. In Sr2+ -Tyrode lacking Ca2+ all three toxins exhibited the same immediate depression followed by facilitation in the rat and mouse diaphragms, but the final blocking activity was only 3-10% with beta-bungarotoxin and crotoxin and was 30% with taipoxin. 6. In Sr2+ -Tyrode, increasing in the rate of nerve stimulation had less accelerating effect on the development of neuromuscular block than in Ca2+ -Tyrode for any of the toxins. 7. Removal of Mg2+ from Sr2+ -Tyrode did not diminish the potency of taipoxin in blocking neuromuscular transmission, suggesting that enzyme activity at the outer surface of the axolemma does not contribute to the neuromuscular blocking action. 8. All of the results indicate that there are close correlations between the presynaptic activities of these toxins and their phospholipid-splitting activities in the cationic environment prevailing in the axoplasm. Apparently the final blocking effect of these toxins is due to phospholipase A action within the nerve terminal."}
{"id": "PMID:198684", "title": "Adrenal cortex adenylate cyclase. In vitro modification of the enzyme by cholera toxin.", "content": "Pretreatment of rat adrenal particulate fractions with cholera toxin in vitro markedly changed the properties of the membrane-bound adenylate cyclase. The basal activity of the enzyme was increased after cholera toxin treatment. The main action of the toxin was on the Vmax of the enzyme. In the absence of added GTP Lineweaver-Burk plots indicate a deviation from normal Michaelis-Menten kinetics with respect to substrate, the slopes being concave downward for control and toxin-treated membranes. Although hormonal stimulation of the enzyme was diminished in toxin-treated membranes, the hormone receptors were still functionally active as revealed after addition of Gpp(NH)p, GTP or GTPgammaS. The response to NaF was decreased in the toxin-treated membranes. Whereas GTP behaves as an antagonist (or a partial agonist with low intrinsic activity) compared to Gpp(NH)p in control membranes, it has similar intrinsic activity as Gpp(NH)p in the toxin-treated membranes. The results indicate that cholera toxin modification of the adenylate cyclase complex is located at the guanyl nucleotide sites or factors controlling the turnover of GTP at these sites. Cholera toxin modification may be a useful tool to investigate the role of guanyl nucleotide sites in the regulation of adenylate cyclase activity.", "contents": "Adrenal cortex adenylate cyclase. In vitro modification of the enzyme by cholera toxin. Pretreatment of rat adrenal particulate fractions with cholera toxin in vitro markedly changed the properties of the membrane-bound adenylate cyclase. The basal activity of the enzyme was increased after cholera toxin treatment. The main action of the toxin was on the Vmax of the enzyme. In the absence of added GTP Lineweaver-Burk plots indicate a deviation from normal Michaelis-Menten kinetics with respect to substrate, the slopes being concave downward for control and toxin-treated membranes. Although hormonal stimulation of the enzyme was diminished in toxin-treated membranes, the hormone receptors were still functionally active as revealed after addition of Gpp(NH)p, GTP or GTPgammaS. The response to NaF was decreased in the toxin-treated membranes. Whereas GTP behaves as an antagonist (or a partial agonist with low intrinsic activity) compared to Gpp(NH)p in control membranes, it has similar intrinsic activity as Gpp(NH)p in the toxin-treated membranes. The results indicate that cholera toxin modification of the adenylate cyclase complex is located at the guanyl nucleotide sites or factors controlling the turnover of GTP at these sites. Cholera toxin modification may be a useful tool to investigate the role of guanyl nucleotide sites in the regulation of adenylate cyclase activity."}
{"id": "PMID:198686", "title": "[Synaptic effects induced in lamprey motor neurons by direct stimulation of individual presynaptic fibers].", "content": "Parallel intracellular recording from giant reticulospinal axons and target motoneurons of the lamprey (Lampetra fluviatilis) revealed unitary synaptic actions produced in the post-synaptic membrane by direct stimulation of individual presynaptic fibres. It is shown that monosynaptic reticulomotoneuronal EPSPs contain both electrical and chemical components which have different synaptic delay, time course, amplitude, sensitivity to Cadeficit and operating characterisitcs. A single motoneuron may receive direct electrotonic inputs from several giant axons. Individual giant axons may affect segmental motoneurons not only via monosynaptic connections but also via additional synaptic relays.", "contents": "[Synaptic effects induced in lamprey motor neurons by direct stimulation of individual presynaptic fibers]. Parallel intracellular recording from giant reticulospinal axons and target motoneurons of the lamprey (Lampetra fluviatilis) revealed unitary synaptic actions produced in the post-synaptic membrane by direct stimulation of individual presynaptic fibres. It is shown that monosynaptic reticulomotoneuronal EPSPs contain both electrical and chemical components which have different synaptic delay, time course, amplitude, sensitivity to Cadeficit and operating characterisitcs. A single motoneuron may receive direct electrotonic inputs from several giant axons. Individual giant axons may affect segmental motoneurons not only via monosynaptic connections but also via additional synaptic relays."}
{"id": "PMID:198687", "title": "Morphological and histochemical properties of human embryonic cells transformed by Rous and polyoma viruses.", "content": "It is shown that human embryonic cells transformed by Rous sarcoma virus (stable cell line 23) and those transformed by polyoma virus (stable cell line P-2) are morphologically distinguished from the normal human embryonic cells. The mitotic activity of P-2 cells was 51% and the mitotic activity of 23 cells was 48%. While the mitosis activity of human embryo fibroblast was 28%. The duration of the mitosis of P-2 cells was 20 hours and that of 23 cells was 18 hr. The duration of the mitotic cycle of human embryo fibroblast was 18 hr. The G1 periods lasted 6 hours for both the cell lines; the S period of P-2 cells lasted 8 hr and the S period of 23 cells was 6 hr. Both the cell lines had a high content of RNA, DNA, protein bound SH-groups, and a high activity of acid phosphatase, acid RNAase and glucose-6-phosphatase. The content of glycogen, and acidic mucopolysaccharides, the activity of NADPH-tetrazolium reductase, succinic dehydrogenase of both the lines were the same as in normal human cells.", "contents": "Morphological and histochemical properties of human embryonic cells transformed by Rous and polyoma viruses. It is shown that human embryonic cells transformed by Rous sarcoma virus (stable cell line 23) and those transformed by polyoma virus (stable cell line P-2) are morphologically distinguished from the normal human embryonic cells. The mitotic activity of P-2 cells was 51% and the mitotic activity of 23 cells was 48%. While the mitosis activity of human embryo fibroblast was 28%. The duration of the mitosis of P-2 cells was 20 hours and that of 23 cells was 18 hr. The duration of the mitotic cycle of human embryo fibroblast was 18 hr. The G1 periods lasted 6 hours for both the cell lines; the S period of P-2 cells lasted 8 hr and the S period of 23 cells was 6 hr. Both the cell lines had a high content of RNA, DNA, protein bound SH-groups, and a high activity of acid phosphatase, acid RNAase and glucose-6-phosphatase. The content of glycogen, and acidic mucopolysaccharides, the activity of NADPH-tetrazolium reductase, succinic dehydrogenase of both the lines were the same as in normal human cells."}
{"id": "PMID:198688", "title": "Notes on the mechanism of postvaccination immunity in Marek's disease.", "content": "The investigated 16th and 45th in vitro passages of non-pathogenic variant 83 of the Kekava strain Marek's disease virus have led in chickens to resistance to Marek's disease by introduction of the above-mentioned virus 14 days before application of pathogenic variant 55 of the Kekava strain Marek's disease virus. Simultaneous administration of both variants of the Kekava strains Marek's disease virus did not protect chickens from the disease. Presence in those variants of the Kekava strain Marek's disease virus of genetic markers manifesting themselves on passaging the virus in chicken fibroblast cultures created the possibility to investigate interrelations between them in the organism of chickens, utilizing in isolation of the virus the method of infecting cultures with chicken fibroblasts. The results of isolation of the virus from the blood cells of vaccinated chickens have shown that in their organism there is interference between those virus variants since the frequency of isolation of the pathogenic virus variant was 3-times lower than that of the apathogenic Kekava strain Marek's disease virus, and both virus variants persisted in various cells. After simultaneous administration of both virus variants to chickens equal amounts of the pathogenic and of the apathogenic Kekava strain Marek's disease virus were isolated from their blood cells. In that case also persistance of both virus variants in one cell may occur.", "contents": "Notes on the mechanism of postvaccination immunity in Marek's disease. The investigated 16th and 45th in vitro passages of non-pathogenic variant 83 of the Kekava strain Marek's disease virus have led in chickens to resistance to Marek's disease by introduction of the above-mentioned virus 14 days before application of pathogenic variant 55 of the Kekava strain Marek's disease virus. Simultaneous administration of both variants of the Kekava strains Marek's disease virus did not protect chickens from the disease. Presence in those variants of the Kekava strain Marek's disease virus of genetic markers manifesting themselves on passaging the virus in chicken fibroblast cultures created the possibility to investigate interrelations between them in the organism of chickens, utilizing in isolation of the virus the method of infecting cultures with chicken fibroblasts. The results of isolation of the virus from the blood cells of vaccinated chickens have shown that in their organism there is interference between those virus variants since the frequency of isolation of the pathogenic virus variant was 3-times lower than that of the apathogenic Kekava strain Marek's disease virus, and both virus variants persisted in various cells. After simultaneous administration of both virus variants to chickens equal amounts of the pathogenic and of the apathogenic Kekava strain Marek's disease virus were isolated from their blood cells. In that case also persistance of both virus variants in one cell may occur."}
{"id": "PMID:198689", "title": "Benzo(a)pyrene free-radicals formation in the presence of butylated hydroxyanisole and their possible importance in carcinogenesis.", "content": "By the method of UV irradiation of benzopyrene in the presence of butylated hydroxyanisole, the benzopyrene EPR spectra was investigated and the possible mechanism by which the carcinogenic activity of benzopyrene in the presence of butylated hydroxyanisole is lowered, was studied.", "contents": "Benzo(a)pyrene free-radicals formation in the presence of butylated hydroxyanisole and their possible importance in carcinogenesis. By the method of UV irradiation of benzopyrene in the presence of butylated hydroxyanisole, the benzopyrene EPR spectra was investigated and the possible mechanism by which the carcinogenic activity of benzopyrene in the presence of butylated hydroxyanisole is lowered, was studied."}
{"id": "PMID:198692", "title": "Observations on the etiology of trigeminal neuralgia, hemifacial spasm, acoustic nerve dysfunction and glossopharyngeal neuralgia. Definitive microsurgical treatment and results in 117 patients.", "content": "Microsurgical observations have been made of the cranial nerve root entry or exit zones 117 patients operated upon for the treatment of hyperactive-hypoactive dysfunction syndromes (trigeminal neuralgia, hemifacial spasm, acoustic nerve dysfunction, and glossopharyngeal neuralgia). Cross-compression or distortion of the appropriate nerve root at its entry or exit zone was noted in all patients. This compression or distortion was usually caused by normal or arteriosclerotic, elongated arterial loops, it was usually relieved by decompressive microsurgical techniques. A small percentage of patients were found to have compression of the nerve root at the entry-exit zone by a tumor, a vein, or some other structural abnormality; they were relieved by tumor excision or other measures as described. Relief was gradual postoperatively if the treated nerve was not stroked or manipulated at operation but it was immediate if the nerve was manipulated. Preoperative evidence of decreased nerve function improved postoperatively.", "contents": "Observations on the etiology of trigeminal neuralgia, hemifacial spasm, acoustic nerve dysfunction and glossopharyngeal neuralgia. Definitive microsurgical treatment and results in 117 patients. Microsurgical observations have been made of the cranial nerve root entry or exit zones 117 patients operated upon for the treatment of hyperactive-hypoactive dysfunction syndromes (trigeminal neuralgia, hemifacial spasm, acoustic nerve dysfunction, and glossopharyngeal neuralgia). Cross-compression or distortion of the appropriate nerve root at its entry or exit zone was noted in all patients. This compression or distortion was usually caused by normal or arteriosclerotic, elongated arterial loops, it was usually relieved by decompressive microsurgical techniques. A small percentage of patients were found to have compression of the nerve root at the entry-exit zone by a tumor, a vein, or some other structural abnormality; they were relieved by tumor excision or other measures as described. Relief was gradual postoperatively if the treated nerve was not stroked or manipulated at operation but it was immediate if the nerve was manipulated. Preoperative evidence of decreased nerve function improved postoperatively."}
{"id": "PMID:198696", "title": "Effect of electrical stimulation of the canine brain stem on the secretion of ACTH and growth hormone (GH).", "content": "The effects of electrical stimulation of the brain stem on ACTH and GH secretion were studied in pentobarbital-anesthetized dogs. Stimulations in or near the subcoeruleus area or ventral ascending noradrenergic pathway inhibited the stress-induced increase in ACTH secretion, while stimulations in other areas of the brain stem did not. No significant changes in GH secretion occurred following stimulation of the subcoeruleus area, ventral ascending noradrenergic pathway or adjacent regions of the canine brain stem. These results are consistent with the hypothesis that there is central noradrenergic input to the hypothalamus which can inhibit ACTH secretion. This input appears to be separate from the postulated noradrenergic input that may increase the secretion of GH.", "contents": "Effect of electrical stimulation of the canine brain stem on the secretion of ACTH and growth hormone (GH). The effects of electrical stimulation of the brain stem on ACTH and GH secretion were studied in pentobarbital-anesthetized dogs. Stimulations in or near the subcoeruleus area or ventral ascending noradrenergic pathway inhibited the stress-induced increase in ACTH secretion, while stimulations in other areas of the brain stem did not. No significant changes in GH secretion occurred following stimulation of the subcoeruleus area, ventral ascending noradrenergic pathway or adjacent regions of the canine brain stem. These results are consistent with the hypothesis that there is central noradrenergic input to the hypothalamus which can inhibit ACTH secretion. This input appears to be separate from the postulated noradrenergic input that may increase the secretion of GH."}
{"id": "PMID:198697", "title": "Effect of electrical stimulation of the canine diencephalon on the secretion of ACTH, growth hormone (GH) and prolactin (P).", "content": "Plasma levels of ACTH, growth hormone (GH), prolactin (Prl) and corticoids were simultaneously monitored before, during and after diencephalic stimulation in 18 pentobarbital-anesthetized dogs. Constant-current, monopolar biphasic stimulation of several regions of the canine ventral medial hypothalamus caused rapid increases in ACTH and corticoid concentrations. No increases in plasma GH were seen during stimulation, but plasma GH increased after the stimulus was turned off when the stimulating electrodes were in the arcuate-median eminence region. Plasma Prl concentration was not increased or decreased by stimulation of the ventral medial hypothalamus, but in 2 instances in 1 dog, it was increased by stimulation of the nucleus supraopticus difusus. The data indicate that different areas in the hypothalamus regulate the secretion of these 3 anterior pituitary (AP) hormones.", "contents": "Effect of electrical stimulation of the canine diencephalon on the secretion of ACTH, growth hormone (GH) and prolactin (P). Plasma levels of ACTH, growth hormone (GH), prolactin (Prl) and corticoids were simultaneously monitored before, during and after diencephalic stimulation in 18 pentobarbital-anesthetized dogs. Constant-current, monopolar biphasic stimulation of several regions of the canine ventral medial hypothalamus caused rapid increases in ACTH and corticoid concentrations. No increases in plasma GH were seen during stimulation, but plasma GH increased after the stimulus was turned off when the stimulating electrodes were in the arcuate-median eminence region. Plasma Prl concentration was not increased or decreased by stimulation of the ventral medial hypothalamus, but in 2 instances in 1 dog, it was increased by stimulation of the nucleus supraopticus difusus. The data indicate that different areas in the hypothalamus regulate the secretion of these 3 anterior pituitary (AP) hormones."}
{"id": "PMID:198700", "title": "The use of coronal scans for computed tomography of the orbits.", "content": "The use of coronal tomograms for CT scanning of the orbits is emphasized and the technic for patient positioning is described. Normal tomographic images are described and the contribution of coronal scans to a correct diagnosis is stressed in the light of 16 pathological cases. Coronal tomograms are especially valuable to show the regions of the orbital floor and roof and complement axial scanning.", "contents": "The use of coronal scans for computed tomography of the orbits. The use of coronal tomograms for CT scanning of the orbits is emphasized and the technic for patient positioning is described. Normal tomographic images are described and the contribution of coronal scans to a correct diagnosis is stressed in the light of 16 pathological cases. Coronal tomograms are especially valuable to show the regions of the orbital floor and roof and complement axial scanning."}
{"id": "PMID:198701", "title": "Neuromuscular blockade with anti-axoplasmic antibodies.", "content": "In the process of developing an immunopharmacologic method for identifying a \"trophic\" protein released from motor nerve terminals, a soluble fraction of peripheral nerve axoplasm was prepared. An attempt was made to eliminate contaminating myelin and basic protein. Antibodies were produced to soluble nerve proteins in all sheep immunized. On boosting, after a 6-week interval, the animals became weak, and some could not stand on the fifth day after injection. A distinct component of neuromuscular blockade was demonstrated electrically and in response to edrophonium. Because this syndrome was (1) in the broadest sense, an experimental allergic neuropathy but produced by a distinctly different antigen than has been utilized previously (the soluble nerve proteins represented the axoplasmic compartment) and (2) a clinical condition associated with a defect in neuromuscular transmission, this may represent a new and potentially important model in the study of neuromuscular and other neurologic diseases.", "contents": "Neuromuscular blockade with anti-axoplasmic antibodies. In the process of developing an immunopharmacologic method for identifying a \"trophic\" protein released from motor nerve terminals, a soluble fraction of peripheral nerve axoplasm was prepared. An attempt was made to eliminate contaminating myelin and basic protein. Antibodies were produced to soluble nerve proteins in all sheep immunized. On boosting, after a 6-week interval, the animals became weak, and some could not stand on the fifth day after injection. A distinct component of neuromuscular blockade was demonstrated electrically and in response to edrophonium. Because this syndrome was (1) in the broadest sense, an experimental allergic neuropathy but produced by a distinctly different antigen than has been utilized previously (the soluble nerve proteins represented the axoplasmic compartment) and (2) a clinical condition associated with a defect in neuromuscular transmission, this may represent a new and potentially important model in the study of neuromuscular and other neurologic diseases."}
{"id": "PMID:198707", "title": "Conjugated estrogens and the overnight dexamethasone suppression test.", "content": "Basal (8:00 AM) serum cortisol levels in peri- or postmenopausal women treated with 0.625 mg daily of conjugated equine estrogens were only slightly higher than pretreatment levels. A 1.25 mg/day dosage resulted in a significant increase in basal serum cortisol levels. In women treated with either dosage, 8:00 AM serum cortisol levels 8 to 10 hours after 1 mg of oral dexamethasone were suppressed to below 5 microgram/100 ml, although there was a significant rise in post-dexamethasone serum cortisol levels in those treated with the higher dosage. It is concluded that while replacement dosages of estrogens increase circulating total serum cortisol levels, they do not interfere with the interpretation of the overnight dexamethasone suppression test.", "contents": "Conjugated estrogens and the overnight dexamethasone suppression test. Basal (8:00 AM) serum cortisol levels in peri- or postmenopausal women treated with 0.625 mg daily of conjugated equine estrogens were only slightly higher than pretreatment levels. A 1.25 mg/day dosage resulted in a significant increase in basal serum cortisol levels. In women treated with either dosage, 8:00 AM serum cortisol levels 8 to 10 hours after 1 mg of oral dexamethasone were suppressed to below 5 microgram/100 ml, although there was a significant rise in post-dexamethasone serum cortisol levels in those treated with the higher dosage. It is concluded that while replacement dosages of estrogens increase circulating total serum cortisol levels, they do not interfere with the interpretation of the overnight dexamethasone suppression test."}
{"id": "PMID:198715", "title": "[Characteristics of the functional maturity of the insular apparatus of the human pancreas during intrauterine development].", "content": "The reactivity of human foetal pancreas was determined by the increase of insulin secretion in vitro in response to the effect of glucose, arginine, theophylline, cyclic AMP and somatotrophic hormone (STH). The results of the experiments have shown that the beta-cells of the islet system in the pancreas of 7-9 weeks old embryos are as yet not able to respond to the main physiological stimulus, glucose, but respond already to cAMP, STH, arginine with glucose. The glands of 10-14 weeks old foetuses are already able to react to glucose and respond to all other stimuli, except arginine. Taken for comparison, the glands of 19-22 weeks old foetuses respond to glucose by the increase of insulin secretion.", "contents": "[Characteristics of the functional maturity of the insular apparatus of the human pancreas during intrauterine development]. The reactivity of human foetal pancreas was determined by the increase of insulin secretion in vitro in response to the effect of glucose, arginine, theophylline, cyclic AMP and somatotrophic hormone (STH). The results of the experiments have shown that the beta-cells of the islet system in the pancreas of 7-9 weeks old embryos are as yet not able to respond to the main physiological stimulus, glucose, but respond already to cAMP, STH, arginine with glucose. The glands of 10-14 weeks old foetuses are already able to react to glucose and respond to all other stimuli, except arginine. Taken for comparison, the glands of 19-22 weeks old foetuses respond to glucose by the increase of insulin secretion."}
{"id": "PMID:198716", "title": "[Effect of thyroid hormones on cytochrome concentration on the liver and heart tissues of chickens during ontogenesis].", "content": "Changes in the concentration of cytochromes c, c1 and a in the liver and heart homogenates during chick pre- and postnatal development were detected by means of low temperature differential spectrometry. At the early stages of development the high content of respiratory enzymes comparable with that in the adult organism is noted. By the end of embryogenesis the content of cytochromes decreased and, subsequently, increased. The injection of thyroxine in the 16-17 days old embryos and 9-10 days old chickes resulted in more distinct changes in the content of respiratory enzymes in mitochondria of the heart, as compared with those of the liver. No changes in the content of cytochromes were recorded after the injection of 6-methyl thiouracyl in the 10 days old embryos, thus suggesting the inactive state of thyroid parenchyma during this period of development.", "contents": "[Effect of thyroid hormones on cytochrome concentration on the liver and heart tissues of chickens during ontogenesis]. Changes in the concentration of cytochromes c, c1 and a in the liver and heart homogenates during chick pre- and postnatal development were detected by means of low temperature differential spectrometry. At the early stages of development the high content of respiratory enzymes comparable with that in the adult organism is noted. By the end of embryogenesis the content of cytochromes decreased and, subsequently, increased. The injection of thyroxine in the 16-17 days old embryos and 9-10 days old chickes resulted in more distinct changes in the content of respiratory enzymes in mitochondria of the heart, as compared with those of the liver. No changes in the content of cytochromes were recorded after the injection of 6-methyl thiouracyl in the 10 days old embryos, thus suggesting the inactive state of thyroid parenchyma during this period of development."}
{"id": "PMID:198717", "title": "[Isoenzyme makeup of the malate dehydrogenase in 2 species of Acetabularia].", "content": "The isozymes of malate dehydrogenase (MDH) were studied by means of electrophoresis in polyacrilamide gel in Acetabularia crenulata and A. mediterranea. The isozyme profile of MDH was shown to be variable in different parts of the plant. Distinct differences in isozyme profiles of MDH between A. crenulata and A. mediteranea were found when studying the cell fractions which consisted mainly of chloroplasts. The chloroplast fraction of A. mediterranea contained 8 isozymes which form 2 groups with different electrophoretic mobility. The chloroplast fraction of A. crenulata contained 9 isozymes. All the isozymes of the first group were common for both the species under study.", "contents": "[Isoenzyme makeup of the malate dehydrogenase in 2 species of Acetabularia]. The isozymes of malate dehydrogenase (MDH) were studied by means of electrophoresis in polyacrilamide gel in Acetabularia crenulata and A. mediterranea. The isozyme profile of MDH was shown to be variable in different parts of the plant. Distinct differences in isozyme profiles of MDH between A. crenulata and A. mediteranea were found when studying the cell fractions which consisted mainly of chloroplasts. The chloroplast fraction of A. mediterranea contained 8 isozymes which form 2 groups with different electrophoretic mobility. The chloroplast fraction of A. crenulata contained 9 isozymes. All the isozymes of the first group were common for both the species under study."}
{"id": "PMID:198718", "title": "[Interrelations of cyclic adenosine monophosphate and calcium in regulating glycogen synthetase in developing skeletal and cardiac muscles in chickens].", "content": "The decrease of glycogen synthetase activity under the effect of Ca++ and cAMP is observed in the skeletal muscles of chick embryos only at the later stages of embryogenesis (15-18 days). In the cardiac muscle the activity of glycogen synthetase is inhibited by Ca++ apparently prior to the 12th day of development, long before the effect of cAMP which appears, as in the skeletal muscles, on the 18th day. Under the combined effect of cAMP and Ca++ in vitro and that of Ca++ and epinephrine in vivo, no additivity was observed. The possibility of Ca++ participation in the realization of catecholamine effect on the glycogen synthetase system of muscle and their interrelations with cAMP are discussed.", "contents": "[Interrelations of cyclic adenosine monophosphate and calcium in regulating glycogen synthetase in developing skeletal and cardiac muscles in chickens]. The decrease of glycogen synthetase activity under the effect of Ca++ and cAMP is observed in the skeletal muscles of chick embryos only at the later stages of embryogenesis (15-18 days). In the cardiac muscle the activity of glycogen synthetase is inhibited by Ca++ apparently prior to the 12th day of development, long before the effect of cAMP which appears, as in the skeletal muscles, on the 18th day. Under the combined effect of cAMP and Ca++ in vitro and that of Ca++ and epinephrine in vivo, no additivity was observed. The possibility of Ca++ participation in the realization of catecholamine effect on the glycogen synthetase system of muscle and their interrelations with cAMP are discussed."}
{"id": "PMID:198719", "title": "Pleomorphic adenomas of the parotid gland resembling mesenchymal tumors.", "content": "Two cases of unusual pleomorphic adenoma of the parotid gland are described. Each showed marked palisaded zones. Distinction from smooth muscle tumors, neurofibromas, and other spindle-cell neoplasms is described.", "contents": "Pleomorphic adenomas of the parotid gland resembling mesenchymal tumors. Two cases of unusual pleomorphic adenoma of the parotid gland are described. Each showed marked palisaded zones. Distinction from smooth muscle tumors, neurofibromas, and other spindle-cell neoplasms is described."}
{"id": "PMID:198720", "title": "Ultrastructural, electron-probe, and microhardness studies of the controversial amorphous areas in the dentin of regional odontodysplasia.", "content": "The amorphous areas, which are gray in sections stained with hematoxylin and eosin and which are a prominent feature in the coronal dentin of the more severely affected cases of regional odontodysplasia, were studied ultrastructurally and with an electron probe and a Vickers microhardnesss tester. The ultrastructural findings confirmed previous histochemical evidence that the amorphous material consists of glycosaminoglycans and represents collagen-free dentinal matrix, that is, ground substance. Phosphoproteins may also present. The ultrastructural examination of nondecalcified material and electron-probe and microhardness tests supported previous microradiographic evidence that the amorphous areas are more heavily mineralized than normal dentin. The boundaries of the amorphous areas were found on ultrastructural examination to be distinct but very irregular.", "contents": "Ultrastructural, electron-probe, and microhardness studies of the controversial amorphous areas in the dentin of regional odontodysplasia. The amorphous areas, which are gray in sections stained with hematoxylin and eosin and which are a prominent feature in the coronal dentin of the more severely affected cases of regional odontodysplasia, were studied ultrastructurally and with an electron probe and a Vickers microhardnesss tester. The ultrastructural findings confirmed previous histochemical evidence that the amorphous material consists of glycosaminoglycans and represents collagen-free dentinal matrix, that is, ground substance. Phosphoproteins may also present. The ultrastructural examination of nondecalcified material and electron-probe and microhardness tests supported previous microradiographic evidence that the amorphous areas are more heavily mineralized than normal dentin. The boundaries of the amorphous areas were found on ultrastructural examination to be distinct but very irregular."}
{"id": "PMID:198722", "title": "Fine structure of a bronchial oncocytoma.", "content": "The fine structure of a bronchial oncocytoma is described. The tumour cells are characterized by abundant, normal sized mitochondria with lamellar cristae. Membrane bound protein granules, which measure 0,1 to 0.5 micron in diameter, are also regularly found. Furthermore, all cell organelles involved in protein synthesis occur in oncocytes. The tumour cells lack basement membranes. The protein storing granules of oncocytes are comparable to peptide hormones storing granules. Positive staining with lead hematoxylin and a faint argentaffin staining suggest that oncocytes in the case studied belong to an oncocytic carcinoid. This view is further substantiated by a high serotonin content of the tumour (50.6 microgram/g wet weight).", "contents": "Fine structure of a bronchial oncocytoma. The fine structure of a bronchial oncocytoma is described. The tumour cells are characterized by abundant, normal sized mitochondria with lamellar cristae. Membrane bound protein granules, which measure 0,1 to 0.5 micron in diameter, are also regularly found. Furthermore, all cell organelles involved in protein synthesis occur in oncocytes. The tumour cells lack basement membranes. The protein storing granules of oncocytes are comparable to peptide hormones storing granules. Positive staining with lead hematoxylin and a faint argentaffin staining suggest that oncocytes in the case studied belong to an oncocytic carcinoid. This view is further substantiated by a high serotonin content of the tumour (50.6 microgram/g wet weight)."}
{"id": "PMID:198723", "title": "[Cerebral gigantism (Sotos-syndrome) (author's transl)].", "content": "Case report of a nine month old girl with Cerebral Gigantism. It is a gigantism syndrome characterized by advanced bone age, a typical craniofacial dysmorphia and a not progredient mental retardation. Etiology and pathogenesis of this syndrome are unknown.", "contents": "[Cerebral gigantism (Sotos-syndrome) (author's transl)]. Case report of a nine month old girl with Cerebral Gigantism. It is a gigantism syndrome characterized by advanced bone age, a typical craniofacial dysmorphia and a not progredient mental retardation. Etiology and pathogenesis of this syndrome are unknown."}
{"id": "PMID:198725", "title": "Observations on the algogenic actions of adenosine compounds on the human blister base preparation.", "content": "The action of the adenyl compounds adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine was studied on the human blister base preparation. All 4 adenyl compounds produced pain which was slow in onset and not maintained. The threshold concentration for pain was of the order of 1-3 micron. The slopes of log concentration:pain intensity plots were relatively shallow and for moderate to severe pain a 100-fold increase of the threshold concentration was required. The adenyl compounds resembled 5-hydroxytryptamine and bradykinin with respect to onset and duration of action but were less potent. On the other hand, for threshold effects they were more potent than acetylcholine or potassium. Evidence was found for an interaction of adenyl compounds with 5-hydroxytryptamine but not with potassium, acetylcholine or bradykinin. Cyclic adenosine 3',5'-monophosphate or the chelation of extracellular calcium or magnesium were shown not to be involved in the algogenic action of adenyl compounds and the action of adenyl compounds on the rabbit isolated jejunum too was found to be unrelated to their algogenic action on the human blister base preparation.", "contents": "Observations on the algogenic actions of adenosine compounds on the human blister base preparation. The action of the adenyl compounds adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine was studied on the human blister base preparation. All 4 adenyl compounds produced pain which was slow in onset and not maintained. The threshold concentration for pain was of the order of 1-3 micron. The slopes of log concentration:pain intensity plots were relatively shallow and for moderate to severe pain a 100-fold increase of the threshold concentration was required. The adenyl compounds resembled 5-hydroxytryptamine and bradykinin with respect to onset and duration of action but were less potent. On the other hand, for threshold effects they were more potent than acetylcholine or potassium. Evidence was found for an interaction of adenyl compounds with 5-hydroxytryptamine but not with potassium, acetylcholine or bradykinin. Cyclic adenosine 3',5'-monophosphate or the chelation of extracellular calcium or magnesium were shown not to be involved in the algogenic action of adenyl compounds and the action of adenyl compounds on the rabbit isolated jejunum too was found to be unrelated to their algogenic action on the human blister base preparation."}
{"id": "PMID:198726", "title": "Longitudinal study of calcium and bone metabolism in paraplegic patients.", "content": "A longitudinal study of bone and calcium metabolism in 28 patients with spinal chord lesion shows an enhancement of bone calcium accretion, generalized to the whole skeleton. The bone calcium turnover rate is more increased in the non-paralysed area during the first 2 months.", "contents": "Longitudinal study of calcium and bone metabolism in paraplegic patients. A longitudinal study of bone and calcium metabolism in 28 patients with spinal chord lesion shows an enhancement of bone calcium accretion, generalized to the whole skeleton. The bone calcium turnover rate is more increased in the non-paralysed area during the first 2 months."}
{"id": "PMID:198730", "title": "The activity of galactose-1-phosphate uridyltransferase and galactokinase in human fetal organs.", "content": "The activity of galactose-1-phosphate uridyltransferase (transferase) and galactokinase in several organs from human fetuses 7-28 weeks old was measured by using radioactive substrates and column chromatography for product identification. The specific activity of transferase and galactokinase increased with gestational age and reached, at the 28th week, a maximal level of 30.0 and 7.9 nmol/min/mg protein (units) in liver, 4.7 and  2.5 units in kidney, 6.0 and 4.0 units in lung, 6.7 and 2.9 units in spleen, 5.2 and 2.6 units in cardiac muscle, and 4.0 and 1.4 units in skeletal muscle, respectively. The activity in brain, on the other hand, remained quite constant with 1.2 units in the case of transferase and 0.5 units in the case of galactokinase during this period. The activities of both enzymes in the liver of children were slightly lower than the highest fetal level during the period of pregnancy studied. Galactokinase activity in fetal erythrocytes was approximately 4 times higher and the transferase activity approximately 30% higher than in adults. The Km value of fetal liver transferase for galactose-1-phosphate was found to be 0.330-0.357 mM and that of galactokinase for galactose, 0.265-0.277 mM.", "contents": "The activity of galactose-1-phosphate uridyltransferase and galactokinase in human fetal organs. The activity of galactose-1-phosphate uridyltransferase (transferase) and galactokinase in several organs from human fetuses 7-28 weeks old was measured by using radioactive substrates and column chromatography for product identification. The specific activity of transferase and galactokinase increased with gestational age and reached, at the 28th week, a maximal level of 30.0 and 7.9 nmol/min/mg protein (units) in liver, 4.7 and  2.5 units in kidney, 6.0 and 4.0 units in lung, 6.7 and 2.9 units in spleen, 5.2 and 2.6 units in cardiac muscle, and 4.0 and 1.4 units in skeletal muscle, respectively. The activity in brain, on the other hand, remained quite constant with 1.2 units in the case of transferase and 0.5 units in the case of galactokinase during this period. The activities of both enzymes in the liver of children were slightly lower than the highest fetal level during the period of pregnancy studied. Galactokinase activity in fetal erythrocytes was approximately 4 times higher and the transferase activity approximately 30% higher than in adults. The Km value of fetal liver transferase for galactose-1-phosphate was found to be 0.330-0.357 mM and that of galactokinase for galactose, 0.265-0.277 mM."}
{"id": "PMID:198732", "title": "Recent advances in pediatric oncology.", "content": "There have been remarkable improvements in our knowledge of how to treat children with cancer and also in the results of treatment. Much of this improvement has come from careful and systematic clinical therapeutic studies. We have learned much about the natural history and some about the biology of childhood cancer. For the future it would seem that major advances are going to come not from clinical therapeutic trials but from combined laboratory and clinical research approaches. Chemotherapy will be the main stay of treatment for the foreseeable future. Immunotherapy may play some role as our knowledge of that modality improves. Basically, however, we need much more understanding of the biology of childhood tumors to effect significant answers in this disease area.", "contents": "Recent advances in pediatric oncology. There have been remarkable improvements in our knowledge of how to treat children with cancer and also in the results of treatment. Much of this improvement has come from careful and systematic clinical therapeutic studies. We have learned much about the natural history and some about the biology of childhood cancer. For the future it would seem that major advances are going to come not from clinical therapeutic trials but from combined laboratory and clinical research approaches. Chemotherapy will be the main stay of treatment for the foreseeable future. Immunotherapy may play some role as our knowledge of that modality improves. Basically, however, we need much more understanding of the biology of childhood tumors to effect significant answers in this disease area."}
{"id": "PMID:198734", "title": "Rapid eye movement sleep, apnea, and cardiac slowing influenced by phenobarbital administration in the neonate.", "content": "Polygraphic recordings were performed in seven preterm infants who had been given phenobarbital (phenobarbitone) to evaluate its effect on neonatal sleep behavior and on the incidence of neurogenic apnea and/or bradycardia. The amount of active sleep, as well as the incidence of apnea and/or cardiac slowing occurring predominantly in active sleep, were decreased at therapeutic serum levels of phenobarbital. With declining serum drug levels, active sleep showed a rebound effect; at the same time, apnea and/or cardiac slowing relapsed. Thus, our previously proposed neurophysiologic concept that neonatal apnea is facilitated by active sleep-inhibitory brain mechanisms seems to be confirmed.", "contents": "Rapid eye movement sleep, apnea, and cardiac slowing influenced by phenobarbital administration in the neonate. Polygraphic recordings were performed in seven preterm infants who had been given phenobarbital (phenobarbitone) to evaluate its effect on neonatal sleep behavior and on the incidence of neurogenic apnea and/or bradycardia. The amount of active sleep, as well as the incidence of apnea and/or cardiac slowing occurring predominantly in active sleep, were decreased at therapeutic serum levels of phenobarbital. With declining serum drug levels, active sleep showed a rebound effect; at the same time, apnea and/or cardiac slowing relapsed. Thus, our previously proposed neurophysiologic concept that neonatal apnea is facilitated by active sleep-inhibitory brain mechanisms seems to be confirmed."}
{"id": "PMID:198740", "title": "The repeating nucleotide sequence in the repetitive mitochondrial DNA from a \"low-density\" petite mutant of yeast.", "content": "The repeating nucleotide sequence of 68 base pairs in the mtDNA from an ethidium-induced cytoplasmic petite mutant of yeast has been determined. For sequence analysis specifically primed and terminated RNA copies, obtained by in vitro transcription of the separated strands, were use. The sequence consists of 66 consecutive AT base pairs flanked by two GC pairs and comprises nearly all of the mutant mitochondrial genome. The sequence, moreover, also represents the first part of wild-type mtDNA sequence so far.", "contents": "The repeating nucleotide sequence in the repetitive mitochondrial DNA from a \"low-density\" petite mutant of yeast. The repeating nucleotide sequence of 68 base pairs in the mtDNA from an ethidium-induced cytoplasmic petite mutant of yeast has been determined. For sequence analysis specifically primed and terminated RNA copies, obtained by in vitro transcription of the separated strands, were use. The sequence consists of 66 consecutive AT base pairs flanked by two GC pairs and comprises nearly all of the mutant mitochondrial genome. The sequence, moreover, also represents the first part of wild-type mtDNA sequence so far."}
{"id": "PMID:198741", "title": "Characterization of human enzymes specific for damaged DNA: resolution of endonuclease for irradiated DNA from an apparent N-glycosidase active on alkylated DNA.", "content": "An endonuclease partially purified from human lymphoblasts, and active against ultraviolet-irradiated DNA, was found to act additionally on DNA damaged by either x-radiation or methylmethanesulfonate. To determine if these activities were truly endonucleolytic, the reaction products were analyzed under conditions that prevented conversion of apurinic or apyrimidinic sites to single-strand breaks. With either ultraviolet- or x-irradiated DNA, strand breakage remained maximal, hence confirming the endonucleolytic character of the enzyme. By contrast, with DNA alkylated with methylmethanesulfonate, strand breakage was sharply reduced. Additional experiments indicated that the activity for alkylated DNA induces strand breaks only in concert with a purified endonuclease specific for apurinic sites, suggesting that it is an N-glycosidase that depurinates alkylated bases. This enzyme was separated from the endonuclease specific for irradiated DNA, by chromatography on DNA-agarose.", "contents": "Characterization of human enzymes specific for damaged DNA: resolution of endonuclease for irradiated DNA from an apparent N-glycosidase active on alkylated DNA. An endonuclease partially purified from human lymphoblasts, and active against ultraviolet-irradiated DNA, was found to act additionally on DNA damaged by either x-radiation or methylmethanesulfonate. To determine if these activities were truly endonucleolytic, the reaction products were analyzed under conditions that prevented conversion of apurinic or apyrimidinic sites to single-strand breaks. With either ultraviolet- or x-irradiated DNA, strand breakage remained maximal, hence confirming the endonucleolytic character of the enzyme. By contrast, with DNA alkylated with methylmethanesulfonate, strand breakage was sharply reduced. Additional experiments indicated that the activity for alkylated DNA induces strand breaks only in concert with a purified endonuclease specific for apurinic sites, suggesting that it is an N-glycosidase that depurinates alkylated bases. This enzyme was separated from the endonuclease specific for irradiated DNA, by chromatography on DNA-agarose."}
{"id": "PMID:198742", "title": "Influences of amino acid, ATP, pyrophosphate and tRNA on binding of aminoalkyl adenylates to isoleucyl-tRNA synthetase from Escherichia coli MRE 600.", "content": "Aminoalcohol-AMP esters, structurally related to the assumed intermediates of the amino acid activation reaction, behave as competitive inhibitors both with respect to the amino acid and ATP, when tested in the ATP-(32P) PPi-exchange or the tRNA-charging reaction. However, closer investigation of the binding of norvalinyl adenylate to isoleucyl-tRNA synthetase from Escherichia coli MRE 600 by an equilibrium method shows that only the amino acid is a true competitor, while ATP cannot displace the ester from binding. Pyrophosphate enhances the stability of the ester-enzyme complex whereas tRNA is without detectable influence.", "contents": "Influences of amino acid, ATP, pyrophosphate and tRNA on binding of aminoalkyl adenylates to isoleucyl-tRNA synthetase from Escherichia coli MRE 600. Aminoalcohol-AMP esters, structurally related to the assumed intermediates of the amino acid activation reaction, behave as competitive inhibitors both with respect to the amino acid and ATP, when tested in the ATP-(32P) PPi-exchange or the tRNA-charging reaction. However, closer investigation of the binding of norvalinyl adenylate to isoleucyl-tRNA synthetase from Escherichia coli MRE 600 by an equilibrium method shows that only the amino acid is a true competitor, while ATP cannot displace the ester from binding. Pyrophosphate enhances the stability of the ester-enzyme complex whereas tRNA is without detectable influence."}
{"id": "PMID:198739", "title": "[Respiratory diseases in poultry caused by viruses--occurrence and diagnosis (author's transl)].", "content": "The highly intensive conditions, that economic necessity has forced upon the poultry industry, have resulted in strongly changed environmental conditions and management which combined with the use of a constantly increasing number of live vaccines has highly complicated clearing up the etiology in diseased flocks. This is true not least as far as respiratory diseases concerns, which thereby often run an atypical course. A review, however, not complete, is given of the occurrence and diagnostic procedures in respiratory diseases caused by viruses, the greatest importance attached to infections caused by adeno- and infectious bronchitis virus.", "contents": "[Respiratory diseases in poultry caused by viruses--occurrence and diagnosis (author's transl)]. The highly intensive conditions, that economic necessity has forced upon the poultry industry, have resulted in strongly changed environmental conditions and management which combined with the use of a constantly increasing number of live vaccines has highly complicated clearing up the etiology in diseased flocks. This is true not least as far as respiratory diseases concerns, which thereby often run an atypical course. A review, however, not complete, is given of the occurrence and diagnostic procedures in respiratory diseases caused by viruses, the greatest importance attached to infections caused by adeno- and infectious bronchitis virus."}
{"id": "PMID:198743", "title": "Restoration by T4 ligase of DNA sequences sensitive to \"flush\" cleaving restriction enzyme.", "content": "Fouteen \"flush\"-ended segments originate from the action of the restriction endonuclease Hae III of Haemophilus aegiptius on the DNA of the colicinogenic factor ColE 1 (A. Oka and M. Takanami, Nature, 264, 191, 1976). They are joined by the T4 polynucleotide ligase. The reaction can be monitored by gel electrophoresis, electron microscopy and resistance to phosphatase of the 5'-32P labelled ends. The joined products are a random recombination of the original segments, and can be cleaved by the same Hae III endonuclease to restore the exact electrophoretic pattern of the Hae III-cut ColE 1 DNA. In a properly diluted mixture of 5'-32P segments treated with T4 ligase, the level of phosphatase resistance is very close to the frequency of circle-formation as determined by electron microscopy: thus, the joining of the \"flush\"-ends involves the formation of circular structures covalently closed in both strands.", "contents": "Restoration by T4 ligase of DNA sequences sensitive to \"flush\" cleaving restriction enzyme. Fouteen \"flush\"-ended segments originate from the action of the restriction endonuclease Hae III of Haemophilus aegiptius on the DNA of the colicinogenic factor ColE 1 (A. Oka and M. Takanami, Nature, 264, 191, 1976). They are joined by the T4 polynucleotide ligase. The reaction can be monitored by gel electrophoresis, electron microscopy and resistance to phosphatase of the 5'-32P labelled ends. The joined products are a random recombination of the original segments, and can be cleaved by the same Hae III endonuclease to restore the exact electrophoretic pattern of the Hae III-cut ColE 1 DNA. In a properly diluted mixture of 5'-32P segments treated with T4 ligase, the level of phosphatase resistance is very close to the frequency of circle-formation as determined by electron microscopy: thus, the joining of the \"flush\"-ends involves the formation of circular structures covalently closed in both strands."}
{"id": "PMID:198744", "title": "Natural occurence of a biopolymer, poly (adenosine diphosphate ribose).", "content": "Evidence for the natural occurrence of poly(adenosine diphosphate ribose) in vivo was obtained using a sensitive radioimmunoassay and poly(adenosine diphosphate ribose) glycohydrolase, which specifically hydrolyzes poly(adenosine diphosphate ribose). Calf thymus, liver, kidney, brain, pancreas and spleen contained poly(adenosine diphosphate ribose). Naturally occurring poly(adenosine diphosphate ribose) in calf thymus is composed of molecules of various chain lengths, like that synthesized by an in vitro system. Calf thymus was estimated to contain about 0.02 microgram/mg DNA of poly(adenosine diphosphate ribose).", "contents": "Natural occurence of a biopolymer, poly (adenosine diphosphate ribose). Evidence for the natural occurrence of poly(adenosine diphosphate ribose) in vivo was obtained using a sensitive radioimmunoassay and poly(adenosine diphosphate ribose) glycohydrolase, which specifically hydrolyzes poly(adenosine diphosphate ribose). Calf thymus, liver, kidney, brain, pancreas and spleen contained poly(adenosine diphosphate ribose). Naturally occurring poly(adenosine diphosphate ribose) in calf thymus is composed of molecules of various chain lengths, like that synthesized by an in vitro system. Calf thymus was estimated to contain about 0.02 microgram/mg DNA of poly(adenosine diphosphate ribose)."}
{"id": "PMID:198745", "title": "Nucleotide sequence of the gene for the major structural protein of SV40 virus.", "content": "We have determined the sequence of the portion of Simian Virus 40 (SV40) that codes for the major structural protein of the virus. The gene contains 361 codons. Synonym codons for an amino acid are not used randomly. The dinucleotide CG occurs only once and there is 2 to 1 preference for uridylic acid in the third position of codons.", "contents": "Nucleotide sequence of the gene for the major structural protein of SV40 virus. We have determined the sequence of the portion of Simian Virus 40 (SV40) that codes for the major structural protein of the virus. The gene contains 361 codons. Synonym codons for an amino acid are not used randomly. The dinucleotide CG occurs only once and there is 2 to 1 preference for uridylic acid in the third position of codons."}
{"id": "PMID:198746", "title": "Comparison of the nucleotide sequence of the messenger RNA for the major structural protein of SV40 with the DNA sequence encoding the amino acids of the protein.", "content": "The 16S late mRNA from SV40 directs the synthesis of the major viral structural protein, VP1. We have compared the oligonucleotides in the 16S mRNA with those that would be present in a transcript of the portion of SV40 DNA coding for VP1. The results indicate that a segment of about 200 nucleotides of RNA transcribed from a distant part of SV40 DNA have become linked to the transcript of VP1 codons by a bond resistant to phenol extraction and denaturation in formamide.", "contents": "Comparison of the nucleotide sequence of the messenger RNA for the major structural protein of SV40 with the DNA sequence encoding the amino acids of the protein. The 16S late mRNA from SV40 directs the synthesis of the major viral structural protein, VP1. We have compared the oligonucleotides in the 16S mRNA with those that would be present in a transcript of the portion of SV40 DNA coding for VP1. The results indicate that a segment of about 200 nucleotides of RNA transcribed from a distant part of SV40 DNA have become linked to the transcript of VP1 codons by a bond resistant to phenol extraction and denaturation in formamide."}
{"id": "PMID:198747", "title": "Nonuniform distribution of DNA repair in chromatin after treatment with methyl methanesulfonate.", "content": "The distribution of methyl methanesulfonate induced DNA repair was measured in mouse mammary cell chromatin by digestion of \"repair labeled\" nuclei with micrococcal nuclease. The results indicate that there is a nonuniform distribution of DNA repair in chromatin. The chromatin fraction digested during the first 5 minutes of incubation with micrococcal nuclease appears to be a primary site of DNA repair after methyl methanesulfoante treatment. The observed nonuniform distribution of DNA repair in chromatin may be due to 1)a nonrandom alkylation of DNA in chromatin by methyl methanesulfonate or 2)areas in chromatin of increased accessibility for the repair enzymes to the DNA lesions.", "contents": "Nonuniform distribution of DNA repair in chromatin after treatment with methyl methanesulfonate. The distribution of methyl methanesulfonate induced DNA repair was measured in mouse mammary cell chromatin by digestion of \"repair labeled\" nuclei with micrococcal nuclease. The results indicate that there is a nonuniform distribution of DNA repair in chromatin. The chromatin fraction digested during the first 5 minutes of incubation with micrococcal nuclease appears to be a primary site of DNA repair after methyl methanesulfoante treatment. The observed nonuniform distribution of DNA repair in chromatin may be due to 1)a nonrandom alkylation of DNA in chromatin by methyl methanesulfonate or 2)areas in chromatin of increased accessibility for the repair enzymes to the DNA lesions."}
{"id": "PMID:198748", "title": "Methylated constituents of Aedes albopictus poly (A)-containing messenger RNA.", "content": "Poly (A)-containing mRNA prepared from cultured mosquito (Aedes albopictus) cells was found to contain methylated 5'-terminal \"caps\" as well as internal m6A residues. Both type I [m7G(5')ppp(5')Xmp] and type II [m7G(5')ppp(5')XmpYmp] caps were present, at molar ratio of ca five to one. All four common RNA bases were represented in the second position (Xm) of the caps, adenine being the most abundant and N6-methyladenine being absent. The four bases were also represented in the third position (Ym), but here uracil was the predominant base. There was approximately one internal m6A residue for every three caps. These studies demonstrate that mRNA from an invertebrate source can have a methylation pattern comparable with that of mammalian cells in it complexity.", "contents": "Methylated constituents of Aedes albopictus poly (A)-containing messenger RNA. Poly (A)-containing mRNA prepared from cultured mosquito (Aedes albopictus) cells was found to contain methylated 5'-terminal \"caps\" as well as internal m6A residues. Both type I [m7G(5')ppp(5')Xmp] and type II [m7G(5')ppp(5')XmpYmp] caps were present, at molar ratio of ca five to one. All four common RNA bases were represented in the second position (Xm) of the caps, adenine being the most abundant and N6-methyladenine being absent. The four bases were also represented in the third position (Ym), but here uracil was the predominant base. There was approximately one internal m6A residue for every three caps. These studies demonstrate that mRNA from an invertebrate source can have a methylation pattern comparable with that of mammalian cells in it complexity."}
{"id": "PMID:198749", "title": "Application of the avidin-biotin method of gene enrichment to the isolation of long double-stranded DNA containing specific gene sequences.", "content": "A method of enriching for long double-stranded segments of eukaryotic DNA carrying particular genes is described. A purified RNA coded for by the gene is covalently attached to biotin via the protein, cytochrome c. This modified RNA is hybridized to total nuclear, double-stranded DNA under conditions that allow the formation of R-loops. Avidin, which has a high affinity for biotin, is covalently attached to polymer spheres. The complexes of avidin-spheres with DNA:RNA-biotin R-loop hybrids band in CsCl at a much lower bouyant density than does free DNA. This density is a function of the length of DNA coupled per avidin-sphere. This method was used to prepare very long double-strands of DNA highly enriched in the coding sequences for the large rRNAs of D. melanogaster and L. donovani and the histone mRNAs of S. purpuratus.", "contents": "Application of the avidin-biotin method of gene enrichment to the isolation of long double-stranded DNA containing specific gene sequences. A method of enriching for long double-stranded segments of eukaryotic DNA carrying particular genes is described. A purified RNA coded for by the gene is covalently attached to biotin via the protein, cytochrome c. This modified RNA is hybridized to total nuclear, double-stranded DNA under conditions that allow the formation of R-loops. Avidin, which has a high affinity for biotin, is covalently attached to polymer spheres. The complexes of avidin-spheres with DNA:RNA-biotin R-loop hybrids band in CsCl at a much lower bouyant density than does free DNA. This density is a function of the length of DNA coupled per avidin-sphere. This method was used to prepare very long double-strands of DNA highly enriched in the coding sequences for the large rRNAs of D. melanogaster and L. donovani and the histone mRNAs of S. purpuratus."}
{"id": "PMID:198750", "title": "DNA synthesis by partially purified replicating simian virus 40 chromosomes.", "content": "We have partially purified replicating simian virus 40 (SV40) chromosomes in a form which allows continued DNA synthesis in vitro. We first prepare a soluble DNA-synthesizing system from SV40-infected monkey cells and then sediment the components through a neutral sucrose gradient of extremely low ionic strength. Replicating SV40 chromosomes isolated from such gradients are capable of continuing DNA synthesis in vitro in the same manner as two crude subnuclear systems we have previously described (4). This indicates that the enzymes and other proteins required for in vitro DNA synthesis are bound to the replicating chromosomes.", "contents": "DNA synthesis by partially purified replicating simian virus 40 chromosomes. We have partially purified replicating simian virus 40 (SV40) chromosomes in a form which allows continued DNA synthesis in vitro. We first prepare a soluble DNA-synthesizing system from SV40-infected monkey cells and then sediment the components through a neutral sucrose gradient of extremely low ionic strength. Replicating SV40 chromosomes isolated from such gradients are capable of continuing DNA synthesis in vitro in the same manner as two crude subnuclear systems we have previously described (4). This indicates that the enzymes and other proteins required for in vitro DNA synthesis are bound to the replicating chromosomes."}
{"id": "PMID:198757", "title": "The preparation of silica gel thin layers with a new apparatus.", "content": "An apparatus for the preparation of uniform thin layer chromatography gel layers is described. The apparatus employs rubber cushion runners to compensate for differences in plate thickness and a gel applicator which functions independently of plate edge variability. Consistently uniform layers are prepared by careful establishment of the plate-to-applicator distance. Silica gel layers averaged 87% of the applied thickness with a variability of +/-2% within a single run and +/-8% between independent runs.", "contents": "The preparation of silica gel thin layers with a new apparatus. An apparatus for the preparation of uniform thin layer chromatography gel layers is described. The apparatus employs rubber cushion runners to compensate for differences in plate thickness and a gel applicator which functions independently of plate edge variability. Consistently uniform layers are prepared by careful establishment of the plate-to-applicator distance. Silica gel layers averaged 87% of the applied thickness with a variability of +/-2% within a single run and +/-8% between independent runs."}
{"id": "PMID:198759", "title": "[Hormonal regulation of lipoate-35S transport into rat liver mitochondria].", "content": "The effect of adrenalectomy, and also of adrenaline, hydrocortisone and ACTH on the rate of lipoate-35S penetration into the mitochondria of the liver was studied in rats. Bilateral adrenalectomy proved to decrease the rate of the lipoate penetration into the organellae significantly; this was more pronounced in female than in the male rats. The capacity of hepatic mitochondria to absorp the lipoic acid was restored under the effect of single adrenaline, hydrocortisone and ACTH injections. Actinomycin D administered to the animals for a period of 3 days in combination with hydrocortisone eliminated the stimulating effect of the hormone on the lipoate transport into the mitochondria of the liver of the intact and adrenalectomized rats completely. The data obtained pointed to the regulating effect of some hormones on the intensity of penetration of lipoate into the biological structures.", "contents": "[Hormonal regulation of lipoate-35S transport into rat liver mitochondria]. The effect of adrenalectomy, and also of adrenaline, hydrocortisone and ACTH on the rate of lipoate-35S penetration into the mitochondria of the liver was studied in rats. Bilateral adrenalectomy proved to decrease the rate of the lipoate penetration into the organellae significantly; this was more pronounced in female than in the male rats. The capacity of hepatic mitochondria to absorp the lipoic acid was restored under the effect of single adrenaline, hydrocortisone and ACTH injections. Actinomycin D administered to the animals for a period of 3 days in combination with hydrocortisone eliminated the stimulating effect of the hormone on the lipoate transport into the mitochondria of the liver of the intact and adrenalectomized rats completely. The data obtained pointed to the regulating effect of some hormones on the intensity of penetration of lipoate into the biological structures."}
{"id": "PMID:198760", "title": "[Mechanism of hypoglycemia in insulinoma].", "content": "A study was made of the capacity of insulinoma to catalyze the splitting of hippuryl-L-arginine (HA) and the contents of proinsulin-like component in the tissues of the tumours and in the blood serum of the patients. As revealed, in the absence of HA splitting by the tumour cytoplasmic fraction in the neutral pH zone there was noted a higher proinsulin-like component both in the tumour tissue and in the blood serum. An increase amount of proinsulin-like component in the blood serum stipulates possibly a more prolonged period of starvation before the occurrence of hypoglycemia, and a less pronounced picture of hypoglycemia in such patients in comparison with the patients whose tumours were capable of splitting HA similarly to the normal islands of Langerhans.", "contents": "[Mechanism of hypoglycemia in insulinoma]. A study was made of the capacity of insulinoma to catalyze the splitting of hippuryl-L-arginine (HA) and the contents of proinsulin-like component in the tissues of the tumours and in the blood serum of the patients. As revealed, in the absence of HA splitting by the tumour cytoplasmic fraction in the neutral pH zone there was noted a higher proinsulin-like component both in the tumour tissue and in the blood serum. An increase amount of proinsulin-like component in the blood serum stipulates possibly a more prolonged period of starvation before the occurrence of hypoglycemia, and a less pronounced picture of hypoglycemia in such patients in comparison with the patients whose tumours were capable of splitting HA similarly to the normal islands of Langerhans."}
{"id": "PMID:198761", "title": "[Disorder of the activity of the cardiovascular system in obesity in children and adolescents].", "content": "The author describes the results of study carried out in 171 children aged from 6 to 14 years suffering from adiposity of the constitutional-exogenous and neuro-endocrine form. A complicated character of hemodynamic dicturbances in adiposity (intensified cardiac activity, hyperdynamia replaced by the hypodynamia of the myocardium syndrome in marked degrees of adiposity, incoordination between the central and the peripheral circulation links is noted. All this points to the early involvement of the heart and the vessels in the pathological process.", "contents": "[Disorder of the activity of the cardiovascular system in obesity in children and adolescents]. The author describes the results of study carried out in 171 children aged from 6 to 14 years suffering from adiposity of the constitutional-exogenous and neuro-endocrine form. A complicated character of hemodynamic dicturbances in adiposity (intensified cardiac activity, hyperdynamia replaced by the hypodynamia of the myocardium syndrome in marked degrees of adiposity, incoordination between the central and the peripheral circulation links is noted. All this points to the early involvement of the heart and the vessels in the pathological process."}
{"id": "PMID:198762", "title": "[Mineralocorticoid and glucocorticoid functions of the adrenal cortex and some mechanisms of their regulation in obesity].", "content": "A study was made of 77 patients with adiposity and a group of healthy persons with normal weight. Patients with adiposity had a significant increase of blood plasma aldosterone level; of decisive role in the formation of secondary hyperaldosteronism was played by the elevation of blood renin level. Apparently activation of the renin-angiotensin system and the associated intensification of mineralocorticoid function of the adrenal glands served as one of the causes of development of arterial hypertension in persons with excessive weight. In adiposity there proved to be an increased rate of cortizol secretion and of 17-OCS excretion with the urine; as to the blood plasma cortizol concentration, it failed to show any significant difference from the normal. Apparently stable blood cortizol level in the patients with adiposity was maintained as a result of intensified ACTH secretion; in these patients reserve possibilities of the adrenocorticosteroid function of the hypophysis were diminished.", "contents": "[Mineralocorticoid and glucocorticoid functions of the adrenal cortex and some mechanisms of their regulation in obesity]. A study was made of 77 patients with adiposity and a group of healthy persons with normal weight. Patients with adiposity had a significant increase of blood plasma aldosterone level; of decisive role in the formation of secondary hyperaldosteronism was played by the elevation of blood renin level. Apparently activation of the renin-angiotensin system and the associated intensification of mineralocorticoid function of the adrenal glands served as one of the causes of development of arterial hypertension in persons with excessive weight. In adiposity there proved to be an increased rate of cortizol secretion and of 17-OCS excretion with the urine; as to the blood plasma cortizol concentration, it failed to show any significant difference from the normal. Apparently stable blood cortizol level in the patients with adiposity was maintained as a result of intensified ACTH secretion; in these patients reserve possibilities of the adrenocorticosteroid function of the hypophysis were diminished."}
{"id": "PMID:198763", "title": "[Correlation of hydrocortisone and corticosterone content in assessing the functional state of the adrenal cortex in varying forms of hypercorticism].", "content": "Separate determination of hydrocortisone and corticosterone in the blood of patients with the hypercorticism symptom-complex showed that elevation of the corticosteroid concentration could occur on account of similar elevation of the concentration of both hormones, or one of the hormones alone. Analogous data were observed in patients after ACTH administration. Dexamethasone administration caused a reduction of the hydrocortisone and corticosterone concentration in patients with Itsenko-Cushing's disease, but to a lesser degree than in healthy individuals. Administration of the preparation to the patients with juvenile dyspituitrism decreased the cortizol level, but corticosterone chiefly; as to the patients with the hypothalamic syndrome--only the cortizol level was reduced, the level of corticosterone remaining unchanged. Thus, the evidence obtained before and after the administration of the ACTH preparations and dexamethasone permitted to assess the adrenal cortex function more fully and to defect disturbances of the corticosteroid secretion of interest of the understanding of the clinical symptoms of the disease.", "contents": "[Correlation of hydrocortisone and corticosterone content in assessing the functional state of the adrenal cortex in varying forms of hypercorticism]. Separate determination of hydrocortisone and corticosterone in the blood of patients with the hypercorticism symptom-complex showed that elevation of the corticosteroid concentration could occur on account of similar elevation of the concentration of both hormones, or one of the hormones alone. Analogous data were observed in patients after ACTH administration. Dexamethasone administration caused a reduction of the hydrocortisone and corticosterone concentration in patients with Itsenko-Cushing's disease, but to a lesser degree than in healthy individuals. Administration of the preparation to the patients with juvenile dyspituitrism decreased the cortizol level, but corticosterone chiefly; as to the patients with the hypothalamic syndrome--only the cortizol level was reduced, the level of corticosterone remaining unchanged. Thus, the evidence obtained before and after the administration of the ACTH preparations and dexamethasone permitted to assess the adrenal cortex function more fully and to defect disturbances of the corticosteroid secretion of interest of the understanding of the clinical symptoms of the disease."}
{"id": "PMID:198764", "title": "[Effect of hypophyseal somatotropic, adrenocorticotropic and thyrotropic hormones on the protein component level in the aortal tissue of hypophysectomized rats].", "content": "The authors investigated changes in the content of collagen, noncollagen proteins, total glycoproteins, glycosaminoglycuronans in the aortic tissue of hypophysectomized rats with due regard for the regulatory effects of STH, ACTH and TTH. Replacement STH therapy led to an increase of oxyproline, hexuronic acids, hexoses in the aortic tissue of the hypophysectomized rats. With the action of ACTH under conditions of hypophysectomy there was a marked increase in the content of glyco- and mucoproteins and a reduction of glycosamines in the aortic tissue. The amount of glycosaminoglycuronans, collagen increased considerably under the effect of TTH in the aortic tissue of the hypophysectomized rats; as to the glyco- and mucoprotein content--in remained unchanged. ACTH, TTH and STH were administered from the 15th to the 21st day after hypophysectomy.", "contents": "[Effect of hypophyseal somatotropic, adrenocorticotropic and thyrotropic hormones on the protein component level in the aortal tissue of hypophysectomized rats]. The authors investigated changes in the content of collagen, noncollagen proteins, total glycoproteins, glycosaminoglycuronans in the aortic tissue of hypophysectomized rats with due regard for the regulatory effects of STH, ACTH and TTH. Replacement STH therapy led to an increase of oxyproline, hexuronic acids, hexoses in the aortic tissue of the hypophysectomized rats. With the action of ACTH under conditions of hypophysectomy there was a marked increase in the content of glyco- and mucoproteins and a reduction of glycosamines in the aortic tissue. The amount of glycosaminoglycuronans, collagen increased considerably under the effect of TTH in the aortic tissue of the hypophysectomized rats; as to the glyco- and mucoprotein content--in remained unchanged. ACTH, TTH and STH were administered from the 15th to the 21st day after hypophysectomy."}
{"id": "PMID:198765", "title": "[Diabetic peripheral polyneuropathy].", "content": "Pain, tactile, vibration and temperature sensitivity, and also electroexcitability of individual nerves were determined. Neuropathy incidence was almost the same among males and females. There was found no association between neuropathy and excessive weight of the patients and the type of treatment. The frequency of affection increased with the advance of age and was maximum (40.4%) in patients aged from 55 to 64 years. The frequency of neuropathy proved to depend on the duration of diabetes. Sensitivity was chiefly distributed by distal and polyneuritic type. Affection of the lower limbs occurred in all the cases. Improvement after the treatment was noted in 69.3% of patients; however, in 13.5% of cases only it was objective in character. The irritative-pain syndrome was the one which yielded to the treatment best. Analysis of the results demonstrated the treatment to be more affective in younger persons with a lesser duration and severity of diabetes. The duration of partial remission constituted from 3 to 13 months. This pointed to the necessity of prophylactic therapeutic courses.", "contents": "[Diabetic peripheral polyneuropathy]. Pain, tactile, vibration and temperature sensitivity, and also electroexcitability of individual nerves were determined. Neuropathy incidence was almost the same among males and females. There was found no association between neuropathy and excessive weight of the patients and the type of treatment. The frequency of affection increased with the advance of age and was maximum (40.4%) in patients aged from 55 to 64 years. The frequency of neuropathy proved to depend on the duration of diabetes. Sensitivity was chiefly distributed by distal and polyneuritic type. Affection of the lower limbs occurred in all the cases. Improvement after the treatment was noted in 69.3% of patients; however, in 13.5% of cases only it was objective in character. The irritative-pain syndrome was the one which yielded to the treatment best. Analysis of the results demonstrated the treatment to be more affective in younger persons with a lesser duration and severity of diabetes. The duration of partial remission constituted from 3 to 13 months. This pointed to the necessity of prophylactic therapeutic courses."}
{"id": "PMID:198766", "title": "[Diagnosis of virilizing ovarian tumors and surgical tactics for their treatment].", "content": "The authors present the results of study of the basic blood testosterone level and of the 17-ketosteroid urinary excretion under conditions of a test with dexamethasone and choriongonin. The results obtained were compared with the results of analogous examination of a group of patients with the virile form of the Stein-Loewenthal's syndrome. Blood testosterone level served as a significant criterion in the diagnosis of virilizing tumours of the testes. Besides, a study was made of the remote results of sparing surgical tactics in the treatment of virilizing tumours of the testes lasting up to 13 years in 37 patients. Favourable results pointed to the benign course of these tumours and justified conservative therapy.", "contents": "[Diagnosis of virilizing ovarian tumors and surgical tactics for their treatment]. The authors present the results of study of the basic blood testosterone level and of the 17-ketosteroid urinary excretion under conditions of a test with dexamethasone and choriongonin. The results obtained were compared with the results of analogous examination of a group of patients with the virile form of the Stein-Loewenthal's syndrome. Blood testosterone level served as a significant criterion in the diagnosis of virilizing tumours of the testes. Besides, a study was made of the remote results of sparing surgical tactics in the treatment of virilizing tumours of the testes lasting up to 13 years in 37 patients. Favourable results pointed to the benign course of these tumours and justified conservative therapy."}
{"id": "PMID:198771", "title": "Oxygen \"pulsed\" cytochrome c oxidase: functional properties and catalytic relevance.", "content": "The kinetics of the reaction of cytochrome c with solubilized mammalian cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) has been studied by a stopped-flow technique under two different experimental situations: (i) the completely oxidized enzyme (resting oxidase as obtained from the preparation) was mixed with reduced cytochrome c, and (ii) the completely reduced enzyme in the presence of reduced cytochrome c was exposed to a \"pulse\" of O2 (pulsed oxidase). Both sets of experiments were performed with either \"limiting\" or \"excess\" O2 (relative to oxidase), in the presence or absence of CO. Both the pre-steady-state events and the steady-state kinetics of cytochrome oxidase are found to be different in the two cases. This shows that the product of the reaction of fully reduced oxidase with O2 (pulsed oxidase) is functionally different from the oxidase as prepared (resting oxidase). These differences are interpreted with the assumption of a different rate of intramolecular electron transfer in the pulsed and resting oxidases. Implications of these experimental findings are discussed in the general framework of a tentative model for the catalytic cycle of the oxidase.", "contents": "Oxygen \"pulsed\" cytochrome c oxidase: functional properties and catalytic relevance. The kinetics of the reaction of cytochrome c with solubilized mammalian cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) has been studied by a stopped-flow technique under two different experimental situations: (i) the completely oxidized enzyme (resting oxidase as obtained from the preparation) was mixed with reduced cytochrome c, and (ii) the completely reduced enzyme in the presence of reduced cytochrome c was exposed to a \"pulse\" of O2 (pulsed oxidase). Both sets of experiments were performed with either \"limiting\" or \"excess\" O2 (relative to oxidase), in the presence or absence of CO. Both the pre-steady-state events and the steady-state kinetics of cytochrome oxidase are found to be different in the two cases. This shows that the product of the reaction of fully reduced oxidase with O2 (pulsed oxidase) is functionally different from the oxidase as prepared (resting oxidase). These differences are interpreted with the assumption of a different rate of intramolecular electron transfer in the pulsed and resting oxidases. Implications of these experimental findings are discussed in the general framework of a tentative model for the catalytic cycle of the oxidase."}
{"id": "PMID:198772", "title": "Analysis of polyoma virus nuclear RNA by mini-blot hybridization.", "content": "The size and sequence composition of virus-specific RNA extracted from the nuclei of mouse cells late during polyoma virus productive infection were studied by blot-hybridization analysis of 32P-labeled RNA fractionated on CH3HgOH/agarose gels. Viral RNA molecules between approximately 0.4 and 4 times the length of a complete transcript of the 5.4-kilobase circular viral DNA were found. Less than 20% of such molecules were polyadenylylated. Although viral RNA of all sizes contained species that together hybridized to the entire polyoma genome, sequences complementary to the late region were more abundant than sequences complementary to the early region in transcripts less than 10-12 kilobases long.", "contents": "Analysis of polyoma virus nuclear RNA by mini-blot hybridization. The size and sequence composition of virus-specific RNA extracted from the nuclei of mouse cells late during polyoma virus productive infection were studied by blot-hybridization analysis of 32P-labeled RNA fractionated on CH3HgOH/agarose gels. Viral RNA molecules between approximately 0.4 and 4 times the length of a complete transcript of the 5.4-kilobase circular viral DNA were found. Less than 20% of such molecules were polyadenylylated. Although viral RNA of all sizes contained species that together hybridized to the entire polyoma genome, sequences complementary to the late region were more abundant than sequences complementary to the early region in transcripts less than 10-12 kilobases long."}
{"id": "PMID:198769", "title": "[Effect of 5alpha-androstan-3beta, 17beta-diol on serum lipids and lipoproteins and the development of experimental atherosclerosis].", "content": "The author studied the influence of testosterone metabolite--5alpha-androstan-3beta,17beta-diol--on the development of hyperlipidemia and atherosclerosis in chinchilla rabbits given cholesterol-free semisynthetic atherogenic diet. The metabolite under study inhibited the development of hypercholesterolemia and hyperbetalipoproteinemia and decreased blood phospholipid content in the blood serum of experimental animals below the initial level. Lipid content in the sum total fraction of pre-beta and beta-lipoproteins decreased under the effect of the mentioned metabolite; there was also a fall in the amount of lipoproteins of low density and their greater saturation with cholesterol. Development of experimental atherosclerosis was intensified.", "contents": "[Effect of 5alpha-androstan-3beta, 17beta-diol on serum lipids and lipoproteins and the development of experimental atherosclerosis]. The author studied the influence of testosterone metabolite--5alpha-androstan-3beta,17beta-diol--on the development of hyperlipidemia and atherosclerosis in chinchilla rabbits given cholesterol-free semisynthetic atherogenic diet. The metabolite under study inhibited the development of hypercholesterolemia and hyperbetalipoproteinemia and decreased blood phospholipid content in the blood serum of experimental animals below the initial level. Lipid content in the sum total fraction of pre-beta and beta-lipoproteins decreased under the effect of the mentioned metabolite; there was also a fall in the amount of lipoproteins of low density and their greater saturation with cholesterol. Development of experimental atherosclerosis was intensified."}
{"id": "PMID:198773", "title": "Enzyme associations in T4 phage DNA precursor synthesis.", "content": "A DIRECT APPROACH IS DESCRIBED TO THE QUESTION: Are enzymes of DNA precursor synthesis organized into a supramolecular structure? This approach involved sedimentation analysis of several T4 phage-coded early enzyme activities in crude lysates of infected Escherichia coli. One-third to one-half of several activities tested-dCMP hydroxymethylase, dTMP synthetase, deoxynucleoside 5'-monophosphate kinase, deoxyuridine triphosphatase, and probably dCMP deaminase, but not dihydrofolate reductase or DNA polymerase-sedimented much more rapidly than expected from molecular weight. About 5% of the host cell nucleoside diphosphate kinase, known to participate in T4 DNA precursor synthesis, cosedimented with these activities. To show that this rapidly sedimenting material represents an organized enzyme complex rather than a nonspecific aggregate, we studied the kinetics of formation of dTTP with dUMP as the initial substrate. This three-step reaction sequence reached its maximal rate within a few seconds when catalyzed by enzymes in the aggregate, whereas an equivalent mixture of uncomplexed enzymes required nearly 20 min before dTTP synthesis reached its maximal rate. The effect of aggregation is evidently to decrease the volume into which intermediates are free to diffuse. Because there is reason to believe that intracellular concentration gradients of DNA precursors exist, the properties of this enzyme aggregate in vitro may help to explain how such gradients are maintained.", "contents": "Enzyme associations in T4 phage DNA precursor synthesis. A DIRECT APPROACH IS DESCRIBED TO THE QUESTION: Are enzymes of DNA precursor synthesis organized into a supramolecular structure? This approach involved sedimentation analysis of several T4 phage-coded early enzyme activities in crude lysates of infected Escherichia coli. One-third to one-half of several activities tested-dCMP hydroxymethylase, dTMP synthetase, deoxynucleoside 5'-monophosphate kinase, deoxyuridine triphosphatase, and probably dCMP deaminase, but not dihydrofolate reductase or DNA polymerase-sedimented much more rapidly than expected from molecular weight. About 5% of the host cell nucleoside diphosphate kinase, known to participate in T4 DNA precursor synthesis, cosedimented with these activities. To show that this rapidly sedimenting material represents an organized enzyme complex rather than a nonspecific aggregate, we studied the kinetics of formation of dTTP with dUMP as the initial substrate. This three-step reaction sequence reached its maximal rate within a few seconds when catalyzed by enzymes in the aggregate, whereas an equivalent mixture of uncomplexed enzymes required nearly 20 min before dTTP synthesis reached its maximal rate. The effect of aggregation is evidently to decrease the volume into which intermediates are free to diffuse. Because there is reason to believe that intracellular concentration gradients of DNA precursors exist, the properties of this enzyme aggregate in vitro may help to explain how such gradients are maintained."}
{"id": "PMID:198774", "title": "Stimulation of RNA synthesis in isolated nuclei by partially purified preparations of simian virus 40 T-antigen.", "content": "T-Antigen was partially purified from nuclei of cells transformed by simian virus 40 (SV 40). When nuclei isolated from either rat liver or quiescent hamster cells were preincubated with T-antigen preparations, there was a marked stimulation of RNA synthesis in an in vitro assay, up to 150% above control levels. The stimulation of RNA synthesis was inhibited by hamster antiserum against T-antigen but not by normal hamster serum. When the T-antigen preparations were fractionated on glycerol gradients, the fractions containing complement-fixing activity with antiserum to T-antigen also had the highest stimulatory activity on nuclear RNA synthesis. T-Antigen was also partially purified from nuclei of cells transformed by a temperature-sensitive A mutant of SV40. When preincubated up to 2 hr at 50 degrees, the T-antigen preparation from these temperature-sensitive A mutants was rapidly inactivated, in terms of both complement-fixing activity and ability to stimulate RNA synthesis in isolated rat liver nuclei. Under the same conditions of preincubation, T-antigen preparations from cells transformed by wild-type SV40 maintained their complement-fixing activity and ability to stimulate RNA synthesis. These results suggest that the biological action of T-antigen may be exerted at the level of transcription.", "contents": "Stimulation of RNA synthesis in isolated nuclei by partially purified preparations of simian virus 40 T-antigen. T-Antigen was partially purified from nuclei of cells transformed by simian virus 40 (SV 40). When nuclei isolated from either rat liver or quiescent hamster cells were preincubated with T-antigen preparations, there was a marked stimulation of RNA synthesis in an in vitro assay, up to 150% above control levels. The stimulation of RNA synthesis was inhibited by hamster antiserum against T-antigen but not by normal hamster serum. When the T-antigen preparations were fractionated on glycerol gradients, the fractions containing complement-fixing activity with antiserum to T-antigen also had the highest stimulatory activity on nuclear RNA synthesis. T-Antigen was also partially purified from nuclei of cells transformed by a temperature-sensitive A mutant of SV40. When preincubated up to 2 hr at 50 degrees, the T-antigen preparation from these temperature-sensitive A mutants was rapidly inactivated, in terms of both complement-fixing activity and ability to stimulate RNA synthesis in isolated rat liver nuclei. Under the same conditions of preincubation, T-antigen preparations from cells transformed by wild-type SV40 maintained their complement-fixing activity and ability to stimulate RNA synthesis. These results suggest that the biological action of T-antigen may be exerted at the level of transcription."}
{"id": "PMID:198775", "title": "Nucleotide phosphotransferase of Escherichia coli: purification by affinity chromatography.", "content": "Improved extraction and purification procedures permit the isolation from Escherichia coli W cells of much larger quantities and of more highly purified preparations of nucleotide phosphotransferase. Of various affinity resins tested for efficiency of purification, columns of agarose/5'-AMP (AGAMP), type 3, proved the best. In this way a 300- to 450-fold purification of the enzyme was achieved in a few steps. The enzyme, which, as reported before, transfers organically bound phosphate to the 2' or 3' hydroxyls of nucleosides and nucleotides, was tested in its behavior toward a series of ribonucleosidonucleotides, namely, CpC, ApA, CpA, and ApC. All were phosphate acceptors, but a detailed comparative study of adenosine and cytidine, 5'-AMP and 5'-CMP, and ApA and ApC revealed peculiar specificities in the relative distribution of the phosphorylated products.", "contents": "Nucleotide phosphotransferase of Escherichia coli: purification by affinity chromatography. Improved extraction and purification procedures permit the isolation from Escherichia coli W cells of much larger quantities and of more highly purified preparations of nucleotide phosphotransferase. Of various affinity resins tested for efficiency of purification, columns of agarose/5'-AMP (AGAMP), type 3, proved the best. In this way a 300- to 450-fold purification of the enzyme was achieved in a few steps. The enzyme, which, as reported before, transfers organically bound phosphate to the 2' or 3' hydroxyls of nucleosides and nucleotides, was tested in its behavior toward a series of ribonucleosidonucleotides, namely, CpC, ApA, CpA, and ApC. All were phosphate acceptors, but a detailed comparative study of adenosine and cytidine, 5'-AMP and 5'-CMP, and ApA and ApC revealed peculiar specificities in the relative distribution of the phosphorylated products."}
{"id": "PMID:198768", "title": "[Functional activity of the adrenal cortex and thymus of mice of strains AKR, C57BL/6, C3H/He and C3Hf].", "content": "The authors studied the relationship between the functional activity of the adrenal cortex before and after the ACTH administration and the thymus mass in AKR, C57BL/6, C3H/He, and C3Hf mice. Blood 11-OCS level of these mice proved to differ in accordance with the differences in the 11-OCS production by the adrenal glands. There was revealed no expected inverse correlative dependence between the basal blood glucocorticoid content and the thymus mass. After ACTH administration the mouse species could be placed thus in order of increasing reaction of the thymus: AKR less than C3Hf less than C3H/He less than C57BL/6; this correlated positively with the level of 11-OCS production by the adrenal glands and basal 11-OCS concentration in the peripheral blood.", "contents": "[Functional activity of the adrenal cortex and thymus of mice of strains AKR, C57BL/6, C3H/He and C3Hf]. The authors studied the relationship between the functional activity of the adrenal cortex before and after the ACTH administration and the thymus mass in AKR, C57BL/6, C3H/He, and C3Hf mice. Blood 11-OCS level of these mice proved to differ in accordance with the differences in the 11-OCS production by the adrenal glands. There was revealed no expected inverse correlative dependence between the basal blood glucocorticoid content and the thymus mass. After ACTH administration the mouse species could be placed thus in order of increasing reaction of the thymus: AKR less than C3Hf less than C3H/He less than C57BL/6; this correlated positively with the level of 11-OCS production by the adrenal glands and basal 11-OCS concentration in the peripheral blood."}
{"id": "PMID:198776", "title": "Frog oocytes synthesize and completely process the precursor polypeptide to virion structural proteins after microinjection of avian myeloblastosis virus RNA.", "content": "After microinjection of Xenopus laevis oocytes with RNA from avian myeloblastosis virus, viral structural proteins p27, p19, p15, and p12 are formed by a sequence of posttranslational cleavages of a high-molecular-weight precursor polypeptide. The 60-70S RNA aggregate or its 30-40S RNA subunits obtained by heat or formamide treatment possess the same ability to serve as template in X. laevis oocytes. The processing pattern of virus-specific precursor polypeptides is the same in X. laevis oocytes as in chick embryo fibroblasts infected with avian myeloblastosis virus, but the processing takes place at a much slower rate.", "contents": "Frog oocytes synthesize and completely process the precursor polypeptide to virion structural proteins after microinjection of avian myeloblastosis virus RNA. After microinjection of Xenopus laevis oocytes with RNA from avian myeloblastosis virus, viral structural proteins p27, p19, p15, and p12 are formed by a sequence of posttranslational cleavages of a high-molecular-weight precursor polypeptide. The 60-70S RNA aggregate or its 30-40S RNA subunits obtained by heat or formamide treatment possess the same ability to serve as template in X. laevis oocytes. The processing pattern of virus-specific precursor polypeptides is the same in X. laevis oocytes as in chick embryo fibroblasts infected with avian myeloblastosis virus, but the processing takes place at a much slower rate."}
{"id": "PMID:198777", "title": "Adenosine 3':5'-cyclic monophosphate- and guanosine 3':5'-cyclic monophosphate-dependent protein kinases: possible homologous proteins.", "content": "The properties of purified mammalian adenosine 3':5'-cyclic monophosphate (cAMP)- and guanosine 3':5'-cyclic monophosphate (cGMP)-dependent protein kinases were compared. Several physical characteristics of the two enzymes were similar, including size, shape, affinity for cyclic nucleotide binding, and K(m) for ATP. In addition, the amino acid composition of the two proteins indicated a close composition homology (70-90%). Both cyclic nucleotide-dependent protein kinases catalyzed phosphorylation of rat liver pyruvate kinase (EC 2.7.1.40) and fructose 1,6-diphosphatase (EC 3.1.3.11), rabbit skeletal muscle glycogen synthase (EC 2.4.1.11) and phosphorylase b kinase (EC 2.7.1.38), and calf thymus histone H(2)b. The phosphorylation of several synthetic peptides and of trypsin-sensitive and trypsin-insensitive sites in glycogen synthase suggested similar recognition sites on the protein substrates for the two kinases. The cAMP-dependent protein kinase was the better catalyst with each protein or peptides substrate. The results suggest that the two enzymes evolved from a common ancestral protein.", "contents": "Adenosine 3':5'-cyclic monophosphate- and guanosine 3':5'-cyclic monophosphate-dependent protein kinases: possible homologous proteins. The properties of purified mammalian adenosine 3':5'-cyclic monophosphate (cAMP)- and guanosine 3':5'-cyclic monophosphate (cGMP)-dependent protein kinases were compared. Several physical characteristics of the two enzymes were similar, including size, shape, affinity for cyclic nucleotide binding, and K(m) for ATP. In addition, the amino acid composition of the two proteins indicated a close composition homology (70-90%). Both cyclic nucleotide-dependent protein kinases catalyzed phosphorylation of rat liver pyruvate kinase (EC 2.7.1.40) and fructose 1,6-diphosphatase (EC 3.1.3.11), rabbit skeletal muscle glycogen synthase (EC 2.4.1.11) and phosphorylase b kinase (EC 2.7.1.38), and calf thymus histone H(2)b. The phosphorylation of several synthetic peptides and of trypsin-sensitive and trypsin-insensitive sites in glycogen synthase suggested similar recognition sites on the protein substrates for the two kinases. The cAMP-dependent protein kinase was the better catalyst with each protein or peptides substrate. The results suggest that the two enzymes evolved from a common ancestral protein."}
{"id": "PMID:198778", "title": "Membrane assembly in vitro: synthesis, glycosylation, and asymmetric insertion of a transmembrane protein.", "content": "Membrane assembly was observed to proceed in cell-free extracts. Specifically, the membrane glycoprotein of vesicular stomatitis virus was synthesized in crude extracts of wheat germ in the presence of membrane vesicles derived from pancreatic endoplasmic reticulum. The resulting glycoprotein spans the lipid bilayer asymmetrically, is glycosylated, and is indistinguishable in these respects from the form of the glycoprotein found in the rough endoplasmic reticulum of virus-infected cells. Both glycosylation and asymmetric transmembrane insertion of the glycoprotein into membranes in vitro require protein synthesis in the presence of membranes. The carboxyl-terminal 5% of the polypeptide chain is located on the external surface of vesicles, corresponding to the cytoplasmic surface of the endoplasmic reticulum in cells. Most, or all, of the amino-terminal portion of the glycoprotein, as well as the protein-bound carbohydrate, appears to be located within the lumen of the membrane vesicles. These findings demonstrate that insertion of this membrane protein occurs during or immediately after protein synthesis. The results are consistent with the concepts that the growing membrane protein is extruded across the endoplasmic reticulum membrane amino terminus first and that glycosylation is restricted to the lumenal surface of the membrane. The cell-free system reported here should prove valuable for studying these processes.", "contents": "Membrane assembly in vitro: synthesis, glycosylation, and asymmetric insertion of a transmembrane protein. Membrane assembly was observed to proceed in cell-free extracts. Specifically, the membrane glycoprotein of vesicular stomatitis virus was synthesized in crude extracts of wheat germ in the presence of membrane vesicles derived from pancreatic endoplasmic reticulum. The resulting glycoprotein spans the lipid bilayer asymmetrically, is glycosylated, and is indistinguishable in these respects from the form of the glycoprotein found in the rough endoplasmic reticulum of virus-infected cells. Both glycosylation and asymmetric transmembrane insertion of the glycoprotein into membranes in vitro require protein synthesis in the presence of membranes. The carboxyl-terminal 5% of the polypeptide chain is located on the external surface of vesicles, corresponding to the cytoplasmic surface of the endoplasmic reticulum in cells. Most, or all, of the amino-terminal portion of the glycoprotein, as well as the protein-bound carbohydrate, appears to be located within the lumen of the membrane vesicles. These findings demonstrate that insertion of this membrane protein occurs during or immediately after protein synthesis. The results are consistent with the concepts that the growing membrane protein is extruded across the endoplasmic reticulum membrane amino terminus first and that glycosylation is restricted to the lumenal surface of the membrane. The cell-free system reported here should prove valuable for studying these processes."}
{"id": "PMID:198779", "title": "Glucocorticoid effect on the level of corticotropin messenger RNA activity in rat pituitary.", "content": "In an attempt to understand the molecular mechanism underlying the depressive effect of glucocorticoids on corticotropin production, the level of corticotropin messenger RNA activity in rat pituitaries was measured with the use of the cell-free protein-synthesizing system derived from wheat germ. The large translation product of corticotropin messenger RNA was identified and quantitated by indirect immunoprecipitation with antibody against corticotropin. The level of corticotropin messenger RNA activity was increased 3- to 6-fold by adrenalectomy. Dexamethasone administration to adrenalectomized rats resulted in a marked suppression of corticotropin messenger RNA activity. Cortisol and corticosterone also exhibited a suppressive effect but were less effective than dexamethasone. In contrast, nonglucocorticoids such as progesterone and aldosterone had no suppressive effect. These results indicate that at least part of the glucocorticoid effect on corticotropin production in the pituitary is exerted at the pretranslational level.", "contents": "Glucocorticoid effect on the level of corticotropin messenger RNA activity in rat pituitary. In an attempt to understand the molecular mechanism underlying the depressive effect of glucocorticoids on corticotropin production, the level of corticotropin messenger RNA activity in rat pituitaries was measured with the use of the cell-free protein-synthesizing system derived from wheat germ. The large translation product of corticotropin messenger RNA was identified and quantitated by indirect immunoprecipitation with antibody against corticotropin. The level of corticotropin messenger RNA activity was increased 3- to 6-fold by adrenalectomy. Dexamethasone administration to adrenalectomized rats resulted in a marked suppression of corticotropin messenger RNA activity. Cortisol and corticosterone also exhibited a suppressive effect but were less effective than dexamethasone. In contrast, nonglucocorticoids such as progesterone and aldosterone had no suppressive effect. These results indicate that at least part of the glucocorticoid effect on corticotropin production in the pituitary is exerted at the pretranslational level."}
{"id": "PMID:198780", "title": "In vitro translation yields a possible Rous sarcoma virus src gene product.", "content": "In vitro translation of Rous sarcoma virus (RSV) virion RNA in the messenger-dependent reticulocyte lysate system yielded polypeptides that were not synthesized by translation of RNA from a transformation-defective deletion mutant of RSV. These RSV-specific products migrated on sodium dodecyl sulfate/polyacrylamide gels as two doublets of approximately 25,000 and 17,000 daltons. Synthesis of these proteins was not sensitive to inhibition by m7GTP; however, synthesis of the 76,000-dalton precursor of the internal structural proteins was sensitive to inhibition by m7GTP. Tryptic peptide maps showed the 25,000- and 17,000-dalton proteins to be related to one another but to be distinct from the 76,000-dalton protein. The 25,000-dalton protein was translated only from a polyadenylylated RNA of approximately 2500 nucleotides, whereas the 76,000-dalton protein was translated from 38S RNA, corresponding to the entire viral genome. A 180,000-dalton protein was also synthesized from 38S RSV virion RNA. From the absence of the 25,000- and 17,000-dalton proteins in the translation products of transformation-defective RSV RNA and the size of their RNA templates, we conclude that these proteins may be derived from coding sequences within the RSV src gene.", "contents": "In vitro translation yields a possible Rous sarcoma virus src gene product. In vitro translation of Rous sarcoma virus (RSV) virion RNA in the messenger-dependent reticulocyte lysate system yielded polypeptides that were not synthesized by translation of RNA from a transformation-defective deletion mutant of RSV. These RSV-specific products migrated on sodium dodecyl sulfate/polyacrylamide gels as two doublets of approximately 25,000 and 17,000 daltons. Synthesis of these proteins was not sensitive to inhibition by m7GTP; however, synthesis of the 76,000-dalton precursor of the internal structural proteins was sensitive to inhibition by m7GTP. Tryptic peptide maps showed the 25,000- and 17,000-dalton proteins to be related to one another but to be distinct from the 76,000-dalton protein. The 25,000-dalton protein was translated only from a polyadenylylated RNA of approximately 2500 nucleotides, whereas the 76,000-dalton protein was translated from 38S RNA, corresponding to the entire viral genome. A 180,000-dalton protein was also synthesized from 38S RSV virion RNA. From the absence of the 25,000- and 17,000-dalton proteins in the translation products of transformation-defective RSV RNA and the size of their RNA templates, we conclude that these proteins may be derived from coding sequences within the RSV src gene."}
{"id": "PMID:198781", "title": "Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site.", "content": "Treatment of turkey erthrocyte membranes with cholera toxin caused an enhancement of the basal and catecholamine-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activities. Both of these activities required the presence of GTP. The toxin effect on the adenylate cyclase activity concided with an inhibition of the catecholamine-stimulated guanosinetriphosphatase activity. Inhibition of the guanosinetriphosphatase, as well as enhancement of the adenylate cyclase activity, showed the same dependence on cholera toxin concentrations, and the effect of the toxin on both activities was dependent on the presence of NAD. It is proposed that continuous GTP hydrolysis at the regulatory guanyl nucleotide site is an essential turn-off mechanism, terminating activation of the adenylate cyclase. Cholera toxin inhibits the turn-off guanosinetriphosphatase reaction and thereby causes activation of the adenylate cyclase. According to this mechanism GTP should activate the toxin-treated preparation of adenylate cyclase, as does the hydrolysis-resistant analog guanosine 5'-(beta,gamma-immino)triphosphate [Gpp(NH)p]. Indeed, the toxin-treated adenylate cyclase was maximally activated, in the presence of isoproternol, by either GTP or Gpp(NH)p, while adenylate cyclase not treated with toxin was stimulated by hormone plus GTP to only one-fifth of the activity achieved with hormone plus Gpp(NH)p. Furthermore, the toxin-treated adenylate cyclase activated by isoproterenol plus GTP remained active for and extended period (half-time of 3 min) upon subsequent addition of the beta-adrenergic blocker, propranolol. The native enzyme, however, was refractory to propranolol only if activated by Gpp(NH)p but not by GTP.", "contents": "Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. Treatment of turkey erthrocyte membranes with cholera toxin caused an enhancement of the basal and catecholamine-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activities. Both of these activities required the presence of GTP. The toxin effect on the adenylate cyclase activity concided with an inhibition of the catecholamine-stimulated guanosinetriphosphatase activity. Inhibition of the guanosinetriphosphatase, as well as enhancement of the adenylate cyclase activity, showed the same dependence on cholera toxin concentrations, and the effect of the toxin on both activities was dependent on the presence of NAD. It is proposed that continuous GTP hydrolysis at the regulatory guanyl nucleotide site is an essential turn-off mechanism, terminating activation of the adenylate cyclase. Cholera toxin inhibits the turn-off guanosinetriphosphatase reaction and thereby causes activation of the adenylate cyclase. According to this mechanism GTP should activate the toxin-treated preparation of adenylate cyclase, as does the hydrolysis-resistant analog guanosine 5'-(beta,gamma-immino)triphosphate [Gpp(NH)p]. Indeed, the toxin-treated adenylate cyclase was maximally activated, in the presence of isoproternol, by either GTP or Gpp(NH)p, while adenylate cyclase not treated with toxin was stimulated by hormone plus GTP to only one-fifth of the activity achieved with hormone plus Gpp(NH)p. Furthermore, the toxin-treated adenylate cyclase activated by isoproterenol plus GTP remained active for and extended period (half-time of 3 min) upon subsequent addition of the beta-adrenergic blocker, propranolol. The native enzyme, however, was refractory to propranolol only if activated by Gpp(NH)p but not by GTP."}
{"id": "PMID:198782", "title": "Mechanism of translational control by hemin in reticulocyte lysates.", "content": "The formation of translational inhibitor (active eIF-2 kinase) from proinhibitor (inactive eIF-2 kinase) in reticulocyte lysates, known to be controlled by hemin, can, as we recently reported, be induced by 3':5'-cyclic AMP(cAMP)-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) or its catalytic subunit. We find that in crude preparations from rabbit reticulocyte lysates, hemin inhibits the conversion of proinhibitor to inhibitor catalyzed by endogenous cAMP-dependent protein kinase upon addition of cAMP, but not that caused by the addition of free protein kinase catalytic subunit. Hemin prevents the binding of cAMP to the regulatory subunit of cAMP-dependent protein kinase and blocks the cAMP-induced dissociation of regulatory and catalytic subunits of the enzyme whereby the enzyme is inactivated. The mechanism by which hemin prevents the formation of the inhibitor and maintains protein synthesis in reticulocyte lysates is thus explained.", "contents": "Mechanism of translational control by hemin in reticulocyte lysates. The formation of translational inhibitor (active eIF-2 kinase) from proinhibitor (inactive eIF-2 kinase) in reticulocyte lysates, known to be controlled by hemin, can, as we recently reported, be induced by 3':5'-cyclic AMP(cAMP)-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) or its catalytic subunit. We find that in crude preparations from rabbit reticulocyte lysates, hemin inhibits the conversion of proinhibitor to inhibitor catalyzed by endogenous cAMP-dependent protein kinase upon addition of cAMP, but not that caused by the addition of free protein kinase catalytic subunit. Hemin prevents the binding of cAMP to the regulatory subunit of cAMP-dependent protein kinase and blocks the cAMP-induced dissociation of regulatory and catalytic subunits of the enzyme whereby the enzyme is inactivated. The mechanism by which hemin prevents the formation of the inhibitor and maintains protein synthesis in reticulocyte lysates is thus explained."}
{"id": "PMID:198783", "title": "Levels of translatable mRNAs for cell surface protein, collagen precursors, and two membrane proteins are altered in Rous sarcoma virus-transformed chick embryo fibroblasts.", "content": "Transformation of chick embryo fibroblasts by Rous sarcoma virus results in decreased amounts of a major cell surface protein and of collagen. To determine the mechanism accounting for the decreased production of these proteins, we have measured the relative amounts of functional mRNAs for these and other transformation-sensitive proteins. Total cellular RNAs extracted from normal cells and from cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus were translated in a cell-free system derived from wheat germ. Analysis of the in vitro translation products of RNAs from normal and transformed chick embryo fibroblasts shows a 5-fold reduction in the translatable mRNA for cell surface protein and a 10-fold reduction in translatable mRNA for two collagen precursors. In addition, increases in functional mRNA are observed for myosin and for two membrane polypeptides with molecular weights of 95,000 and 78,000; the latter two proteins increase on transformation, but the increases are in large part secondary to the depletion of glucose from the medium of transformed cells. Our data suggest that some of the major cellular changes induced by oncogenic viruses are due to changes in the activity of specific cellular genes.", "contents": "Levels of translatable mRNAs for cell surface protein, collagen precursors, and two membrane proteins are altered in Rous sarcoma virus-transformed chick embryo fibroblasts. Transformation of chick embryo fibroblasts by Rous sarcoma virus results in decreased amounts of a major cell surface protein and of collagen. To determine the mechanism accounting for the decreased production of these proteins, we have measured the relative amounts of functional mRNAs for these and other transformation-sensitive proteins. Total cellular RNAs extracted from normal cells and from cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus were translated in a cell-free system derived from wheat germ. Analysis of the in vitro translation products of RNAs from normal and transformed chick embryo fibroblasts shows a 5-fold reduction in the translatable mRNA for cell surface protein and a 10-fold reduction in translatable mRNA for two collagen precursors. In addition, increases in functional mRNA are observed for myosin and for two membrane polypeptides with molecular weights of 95,000 and 78,000; the latter two proteins increase on transformation, but the increases are in large part secondary to the depletion of glucose from the medium of transformed cells. Our data suggest that some of the major cellular changes induced by oncogenic viruses are due to changes in the activity of specific cellular genes."}
{"id": "PMID:198784", "title": "Effects of colchicine on cyclic AMP levels in human leukocytes.", "content": "The increase in human leukocyte adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels seen in response to various substances was markedly potentiated by colchicine and other agents that affect microtubule assembly. Addition of dl-isoproterenol (2 muM) or prostaglandin E(1) (10 muM), together with the phosphodiesterase inhibitor isobutylmethylxanthine (1 mM), caused a much greater increase in cyclic AMP in colchicine-pretreated cells than in control cells. With isoproterenol (2 muM) plus isobutylmethylaxanthine (1 mM), cyclic AMP levels rose about 3-fold but, in combination with colchicine, these drugs caused a more than 15-fold increase in cyclic AMP. The effects of colchicine were both time- and dose-dependent; they could be seen within 1 min after addition of colchicine or at concentrations as low as 10 nM. In addition to its potentiation of hormonally induced increases in cyclic AMP levels, colchicine also potentiated the effect of isobutylmethylxanthine alone on leukocyte cyclic AMP levels. Vinblastine, vincristine, podophyllotoxin, and oncodazole all had effects similar to those of colchicine but lumicolchicine did not. The data suggest that cytoplasmic microtubules interact with the leukocyte plasma membrane to impose constraints on the expression of hormone-sensitive adenylate cyclase; the therapeutic effects of colchicine may depend in part upon the relaxation of such constraints. Moreover, the synergism described here between colchicine-like agents and hormones is of potential therapeutic importance in clinical conditions in which either alkaloid or hormone has been useful separately.", "contents": "Effects of colchicine on cyclic AMP levels in human leukocytes. The increase in human leukocyte adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels seen in response to various substances was markedly potentiated by colchicine and other agents that affect microtubule assembly. Addition of dl-isoproterenol (2 muM) or prostaglandin E(1) (10 muM), together with the phosphodiesterase inhibitor isobutylmethylxanthine (1 mM), caused a much greater increase in cyclic AMP in colchicine-pretreated cells than in control cells. With isoproterenol (2 muM) plus isobutylmethylaxanthine (1 mM), cyclic AMP levels rose about 3-fold but, in combination with colchicine, these drugs caused a more than 15-fold increase in cyclic AMP. The effects of colchicine were both time- and dose-dependent; they could be seen within 1 min after addition of colchicine or at concentrations as low as 10 nM. In addition to its potentiation of hormonally induced increases in cyclic AMP levels, colchicine also potentiated the effect of isobutylmethylxanthine alone on leukocyte cyclic AMP levels. Vinblastine, vincristine, podophyllotoxin, and oncodazole all had effects similar to those of colchicine but lumicolchicine did not. The data suggest that cytoplasmic microtubules interact with the leukocyte plasma membrane to impose constraints on the expression of hormone-sensitive adenylate cyclase; the therapeutic effects of colchicine may depend in part upon the relaxation of such constraints. Moreover, the synergism described here between colchicine-like agents and hormones is of potential therapeutic importance in clinical conditions in which either alkaloid or hormone has been useful separately."}
{"id": "PMID:198785", "title": "Intermediate role of adenosine 3':5'-cyclic monophosphate and protein kinase during gonadotropin-induced steroidogenesis in testicular interstitial cells.", "content": "Discrepancies between adenosine 3':5'-cyclic monophosphate (cAMP) and steroid production have been frequently observed in isolated target cells stimulated by low concentrations of trophic hormone. This dissociation is particularly marked in the interstitial cells of the testis, where testosterone production is elicited by gonadotropin concentrations in the picomolar range. Because of these observations, and a disparity between steroidogenesis and protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) activation in Leydig cells, the role of cAMP as a mediator of the acute steroidogenic response has been questioned. This problem has been further analyzed by assay of free and occupied cAMP-binding sites of the regulatory subunit of protein kinase in basal and hormone-stimulated cells. Free sites were measured by a [(3)H]-cAMP-binding assay, and occupied sites were measured by radioimmunoassay of endogenous cAMP eluted from receptor protein. After stimulation of purified Leydig cells with 0.1-10 pM human chorionic gonadotropin, a dose-dependent decrease in available [(3)H]cAMP-binding sites was observed, with no change in binding affinity. The reduction in cAMP-binding sites was equivalent to the increase in occupancy of cAMP receptors by endogenous nucleotide formed during gonadotropin action. Fractional occupancy of cAMP receptors rose progressively from basal values of 0.2-0.40 to full saturation as intracellular cAMP rose 10- to 30-fold during hormone stimulation. The testosterone dose-response curve was coincident with the initial part of the cAMP-receptor occupancy curve. These changes in endogenous cAMP binding to the regulatory subunit were accompanied by a significant increase in protein kinase activity in gonadotropin-stimulated Leydig cells. These observations provide direct evidence for the role of cAMP and protein kinase during hormonal activation of steroidogenesis in the Leydig cell by low concentrations of gonadotropin.", "contents": "Intermediate role of adenosine 3':5'-cyclic monophosphate and protein kinase during gonadotropin-induced steroidogenesis in testicular interstitial cells. Discrepancies between adenosine 3':5'-cyclic monophosphate (cAMP) and steroid production have been frequently observed in isolated target cells stimulated by low concentrations of trophic hormone. This dissociation is particularly marked in the interstitial cells of the testis, where testosterone production is elicited by gonadotropin concentrations in the picomolar range. Because of these observations, and a disparity between steroidogenesis and protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) activation in Leydig cells, the role of cAMP as a mediator of the acute steroidogenic response has been questioned. This problem has been further analyzed by assay of free and occupied cAMP-binding sites of the regulatory subunit of protein kinase in basal and hormone-stimulated cells. Free sites were measured by a [(3)H]-cAMP-binding assay, and occupied sites were measured by radioimmunoassay of endogenous cAMP eluted from receptor protein. After stimulation of purified Leydig cells with 0.1-10 pM human chorionic gonadotropin, a dose-dependent decrease in available [(3)H]cAMP-binding sites was observed, with no change in binding affinity. The reduction in cAMP-binding sites was equivalent to the increase in occupancy of cAMP receptors by endogenous nucleotide formed during gonadotropin action. Fractional occupancy of cAMP receptors rose progressively from basal values of 0.2-0.40 to full saturation as intracellular cAMP rose 10- to 30-fold during hormone stimulation. The testosterone dose-response curve was coincident with the initial part of the cAMP-receptor occupancy curve. These changes in endogenous cAMP binding to the regulatory subunit were accompanied by a significant increase in protein kinase activity in gonadotropin-stimulated Leydig cells. These observations provide direct evidence for the role of cAMP and protein kinase during hormonal activation of steroidogenesis in the Leydig cell by low concentrations of gonadotropin."}
{"id": "PMID:198786", "title": "Changes in surface properties of normal and transformed cells caused by tunicamycin, an inhibitor of protein glycosylation.", "content": "Normal and virally transformed mouse (3T3) and human (WI-38) cells were treated with tunicamycin, an inhibitor of lipid-carrier-dependent glycosylation of proteins. Incubation of cells with tunicamycin (1 microgram/ml) caused detachment and death of simian virus 40- and polyoma-transformed cells within 24 hr; these effects were not seen with nontransformed cell lines. However, the proliferation of 3T3 cells was inhibited by tunicamycin and, after a few days, a distinct change from an epithelioid to an abnormally elongated shape was observed. Both inhibition of growth and the morphological changes were reversible. A marked decrease in concanavalin A agglutinability was observed in virally transformed cells treated with tunicamycin (0.5 microgram/ml), but agglutination by wheat germ agglutinin or soybean agglutinin was unaffected. Analysis of biosynthetically labeled proteins showed that a high-molecular-weight protein, presumed to be related to fibronectin, is markedly reduced in the medium of cells cultured in the presence of tunicamycin. These results suggest that tunicamycin interferes with the insertion or function of one or more cell-surface glycoproteins. Such cell-surface changes could affect a number of cellular properties, including attachment, cell shape, and agglutinability by some lectins.", "contents": "Changes in surface properties of normal and transformed cells caused by tunicamycin, an inhibitor of protein glycosylation. Normal and virally transformed mouse (3T3) and human (WI-38) cells were treated with tunicamycin, an inhibitor of lipid-carrier-dependent glycosylation of proteins. Incubation of cells with tunicamycin (1 microgram/ml) caused detachment and death of simian virus 40- and polyoma-transformed cells within 24 hr; these effects were not seen with nontransformed cell lines. However, the proliferation of 3T3 cells was inhibited by tunicamycin and, after a few days, a distinct change from an epithelioid to an abnormally elongated shape was observed. Both inhibition of growth and the morphological changes were reversible. A marked decrease in concanavalin A agglutinability was observed in virally transformed cells treated with tunicamycin (0.5 microgram/ml), but agglutination by wheat germ agglutinin or soybean agglutinin was unaffected. Analysis of biosynthetically labeled proteins showed that a high-molecular-weight protein, presumed to be related to fibronectin, is markedly reduced in the medium of cells cultured in the presence of tunicamycin. These results suggest that tunicamycin interferes with the insertion or function of one or more cell-surface glycoproteins. Such cell-surface changes could affect a number of cellular properties, including attachment, cell shape, and agglutinability by some lectins."}
{"id": "PMID:198787", "title": "Biological properties of poliovirus encapsulated in lipid vesicles: antibody resistance and infectivity in virus-resistant cells.", "content": "We present evidence that poliovirus can be encapsulated in synthetic large phospholipid vesicles. The virus associated with the vesicles is found to be (i) resistant to antiserum against poliovirus and (ii) infectious for cells that are normally resistant to virus infection because of a membrane restriction. Our interpretation of these results is that the virus is entrapped in the interior aqueous space of the vesicles and that this vesicle-associated virus is introduced directly into the cytoplasm of the cells via fusion of the vesicles with the cellular plasma membrane, bypassing the surface receptor-mediated restriction.", "contents": "Biological properties of poliovirus encapsulated in lipid vesicles: antibody resistance and infectivity in virus-resistant cells. We present evidence that poliovirus can be encapsulated in synthetic large phospholipid vesicles. The virus associated with the vesicles is found to be (i) resistant to antiserum against poliovirus and (ii) infectious for cells that are normally resistant to virus infection because of a membrane restriction. Our interpretation of these results is that the virus is entrapped in the interior aqueous space of the vesicles and that this vesicle-associated virus is introduced directly into the cytoplasm of the cells via fusion of the vesicles with the cellular plasma membrane, bypassing the surface receptor-mediated restriction."}
{"id": "PMID:198788", "title": "Genetic analysis of host range mutant viruses suggests an uncoating defect in simian virus 40-resistant monkey cells.", "content": "Host range mutations that permit simian virus 40 (SV40) to grow with increased efficiency on SV40-resistant monkey cells have been positioned within the viral B/C gene by a mapping method that relies on the coupling of specific DNA fragments. Pairs of restriction endonucleases that each cleave SV40 DNA at only one site were used to generate pairs of specific DNA fragments. Corresponding pairs of fragments were purified from host range mutant and wild-type DNA and joined in known combinations to determine the location of the host range mutations. The map position of the host range mutations was confirmed by using the same technique to generate and couple genetically marked viral DNA fragments to produce the predicted double mutants. Three different double mutants were constructed that carry both host range and temperature-sensitive A mutations. The mutations in three independently isolated host range mutant viruses are located at very close, perhaps identical, sites, because no wild type viruses were produced from the cell-mediated repair of pairwise heteroduplexes between them. The location of these host range mutations suggests that their phenotype results from mutational alteration of the major capsid protein, the product of the B/C gene. In addition it was demonstrated that monkey cells can efficiently join appropriate pairs of restriction endonuclease fragments intracellularly to produce infectious genomes. That reaction has been partially characterized. The general utility of fragment coupling (in vitro and in vivo) and heteroduplex repair for constructing and analyzing multiple mutants of SV40 is discussed.", "contents": "Genetic analysis of host range mutant viruses suggests an uncoating defect in simian virus 40-resistant monkey cells. Host range mutations that permit simian virus 40 (SV40) to grow with increased efficiency on SV40-resistant monkey cells have been positioned within the viral B/C gene by a mapping method that relies on the coupling of specific DNA fragments. Pairs of restriction endonucleases that each cleave SV40 DNA at only one site were used to generate pairs of specific DNA fragments. Corresponding pairs of fragments were purified from host range mutant and wild-type DNA and joined in known combinations to determine the location of the host range mutations. The map position of the host range mutations was confirmed by using the same technique to generate and couple genetically marked viral DNA fragments to produce the predicted double mutants. Three different double mutants were constructed that carry both host range and temperature-sensitive A mutations. The mutations in three independently isolated host range mutant viruses are located at very close, perhaps identical, sites, because no wild type viruses were produced from the cell-mediated repair of pairwise heteroduplexes between them. The location of these host range mutations suggests that their phenotype results from mutational alteration of the major capsid protein, the product of the B/C gene. In addition it was demonstrated that monkey cells can efficiently join appropriate pairs of restriction endonuclease fragments intracellularly to produce infectious genomes. That reaction has been partially characterized. The general utility of fragment coupling (in vitro and in vivo) and heteroduplex repair for constructing and analyzing multiple mutants of SV40 is discussed."}
{"id": "PMID:198789", "title": "Membrane-controlled depletion of complement activity by spin-label-specific IgM.", "content": "Complement depletion mediated by high molecular weight (IgM) rabbit antibodies specifically bound to spin-label lipid haptens dispersed in model membranes is controlled by various physical attributes of those membranes other than the total number of exposed determinants that they provide. Carrier lipids used at 32 degrees were (i) a \"fluid\" phosphatidylcholine (PC), (ii) a \"solid\" PC, and (iii) a cholesterol/PC mixture. The concentration of hapten in the plane of the membranes (two-dimensional concentration) was varied while the overall hapten molarity (three-dimensional concentration) was kept constant. Both specific binding and the efficiency of depletion by IgM are markedly enhanced by systematically decreasing the average distance between haptens (infinity --> 26 A). Heterogeneous distribution was found to be more favorable than a random homogeneous distribution of the same number of haptens in the same total quantity of lipids. IgM efficiency is also markedly increased by the inclusion of cholesterol in PC membranes, an effect thought to result from enhanced projection of the determinant from the surface of the membrane and hence increased accessibility to the antibody-binding site. Furthermore, the efficiency of IgM was increased by using haptens dispersed in fluid rather than in solid PC membranes. The results are consistent with the hypothesis that IgM molecules must be bound to a critical multiple of antigenic determinants at a membrane surface in order to induce complement-mediated attack and that subtle variation of the physical state of membrane antigens can be the crucial factor in determining the outcome of this type of efferent immune response.", "contents": "Membrane-controlled depletion of complement activity by spin-label-specific IgM. Complement depletion mediated by high molecular weight (IgM) rabbit antibodies specifically bound to spin-label lipid haptens dispersed in model membranes is controlled by various physical attributes of those membranes other than the total number of exposed determinants that they provide. Carrier lipids used at 32 degrees were (i) a \"fluid\" phosphatidylcholine (PC), (ii) a \"solid\" PC, and (iii) a cholesterol/PC mixture. The concentration of hapten in the plane of the membranes (two-dimensional concentration) was varied while the overall hapten molarity (three-dimensional concentration) was kept constant. Both specific binding and the efficiency of depletion by IgM are markedly enhanced by systematically decreasing the average distance between haptens (infinity --> 26 A). Heterogeneous distribution was found to be more favorable than a random homogeneous distribution of the same number of haptens in the same total quantity of lipids. IgM efficiency is also markedly increased by the inclusion of cholesterol in PC membranes, an effect thought to result from enhanced projection of the determinant from the surface of the membrane and hence increased accessibility to the antibody-binding site. Furthermore, the efficiency of IgM was increased by using haptens dispersed in fluid rather than in solid PC membranes. The results are consistent with the hypothesis that IgM molecules must be bound to a critical multiple of antigenic determinants at a membrane surface in order to induce complement-mediated attack and that subtle variation of the physical state of membrane antigens can be the crucial factor in determining the outcome of this type of efferent immune response."}
{"id": "PMID:198790", "title": "Immunohistochemical localization of 3':5'-cyclic AMP and 3':5'-cyclic GMP in rat renal cortex: effect of parathyroid hormone.", "content": "Adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) were localized in cells of rat kidney cortex by an immunocytochemical technique before and after perfusion with parathyroid hormone (PTH). In control tissues the cAMP antiserum detected approximately the same intensity of fluorescence in cytoplasmic epithelial cell elements of cortical tubules and glomeruli (cells of Bowman's capsule and podocytes). PTH increased fluorescence in these glomerular cells and increased cAMP fluorescence in cytoplasmic granules in proximal tubular cells. These granules, whose structure has not been identified, were located predominantly on the luminal side of the tubular cells. In control rats, the renal cortical fluorescence detected with the cGMP antiserum was more pronounced in glomeruli (predominantly in the mesangial areas) and lesser amounts of fluorescence were observed in tubules. After PTH treatment, cGMP fluorescence increased in glomeruli and in renal tubular cells. A bright linear pattern of fluorescence was found in the area of the tubular luminal membrane. Perfusion with PTH caused relatively small increases in total tissue cAMP and no consistent increases in total tissue cGMP. Our observations suggest that both cAMP and cGMP are involved in the glomerular and tubular responses to PTH and point out the added dimension that this immunocytochemical technique brings to studies of cyclic nucleotide dynamics in heterogeneous tissues.", "contents": "Immunohistochemical localization of 3':5'-cyclic AMP and 3':5'-cyclic GMP in rat renal cortex: effect of parathyroid hormone. Adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) were localized in cells of rat kidney cortex by an immunocytochemical technique before and after perfusion with parathyroid hormone (PTH). In control tissues the cAMP antiserum detected approximately the same intensity of fluorescence in cytoplasmic epithelial cell elements of cortical tubules and glomeruli (cells of Bowman's capsule and podocytes). PTH increased fluorescence in these glomerular cells and increased cAMP fluorescence in cytoplasmic granules in proximal tubular cells. These granules, whose structure has not been identified, were located predominantly on the luminal side of the tubular cells. In control rats, the renal cortical fluorescence detected with the cGMP antiserum was more pronounced in glomeruli (predominantly in the mesangial areas) and lesser amounts of fluorescence were observed in tubules. After PTH treatment, cGMP fluorescence increased in glomeruli and in renal tubular cells. A bright linear pattern of fluorescence was found in the area of the tubular luminal membrane. Perfusion with PTH caused relatively small increases in total tissue cAMP and no consistent increases in total tissue cGMP. Our observations suggest that both cAMP and cGMP are involved in the glomerular and tubular responses to PTH and point out the added dimension that this immunocytochemical technique brings to studies of cyclic nucleotide dynamics in heterogeneous tissues."}
{"id": "PMID:198791", "title": "Supercoiled circular DNA of an insect granulosis virus.", "content": "The DNA of the granulosis virus of the Indian meal moth, Plodia interpunctella, was characterized by physical chemical and electron microscopic techniques. Twenty-five percent of the DNA extracted from purified virus was isolated as supercoiled circular molecules. The remaining 75% consisted of relaxed circular molecules. These molecular forms were indicated by the production of two radioactive bands during sedimentation of (3)H-labeled granulosis virus DNA in alkaline sucrose gradients or in equilibrium density gradients of neutral cesium chloride/propidium iodide. Electron microscopic visualization of the DNA that banded at the higher density in the latter gradients revealed supercoiled structures whereas that of DNA that banded at the lower density demonstrated relaxed circular molecules. The superhelical molecules were converted to relaxed circles by treatment with pancreatic DNase. The molecular weight of the viral DNA was calculated to be 81 x 10(6) by sedimentation in neutral sucrose and 78 x 10(6) by sedimentation in alkaline sucrose. The molecular weight estimated from length measurements in electron micrographs was 76 x 10(6). The buoyant density of the granulosis virus DNA was 1.703 g/cm(3) and that of its insect host DNA was 1.697 g/cm(3). Equilibrium sedimentation in cesium chloride and thermal denaturation indicated G + C contents of 44% and 39% for the viral and host DNA, respectively.", "contents": "Supercoiled circular DNA of an insect granulosis virus. The DNA of the granulosis virus of the Indian meal moth, Plodia interpunctella, was characterized by physical chemical and electron microscopic techniques. Twenty-five percent of the DNA extracted from purified virus was isolated as supercoiled circular molecules. The remaining 75% consisted of relaxed circular molecules. These molecular forms were indicated by the production of two radioactive bands during sedimentation of (3)H-labeled granulosis virus DNA in alkaline sucrose gradients or in equilibrium density gradients of neutral cesium chloride/propidium iodide. Electron microscopic visualization of the DNA that banded at the higher density in the latter gradients revealed supercoiled structures whereas that of DNA that banded at the lower density demonstrated relaxed circular molecules. The superhelical molecules were converted to relaxed circles by treatment with pancreatic DNase. The molecular weight of the viral DNA was calculated to be 81 x 10(6) by sedimentation in neutral sucrose and 78 x 10(6) by sedimentation in alkaline sucrose. The molecular weight estimated from length measurements in electron micrographs was 76 x 10(6). The buoyant density of the granulosis virus DNA was 1.703 g/cm(3) and that of its insect host DNA was 1.697 g/cm(3). Equilibrium sedimentation in cesium chloride and thermal denaturation indicated G + C contents of 44% and 39% for the viral and host DNA, respectively."}
{"id": "PMID:198792", "title": "Mechanisms by which diazepam, muscimol, and other drugs change the content of cGMP in cerebellar cortex.", "content": "THE CEREBELLUM CONSISTS OF TWO PARTS: the cerebellar nuclei whose connections to the various parts of the central nervous system coordinate muscle movements, and the cerebellar cortex which exerts an inhibitory influence on the cerebellar nuclei through the release of gamma-aminobutyric acid (gammaAbu) from Purkinje cells. The activity of Purkinje cells is regulated by two excitatory inputs to the cerebellar cortex-the climbing and mossy fibers-and by a neuronal network within the cortex which inhibits the activity of Purkinje cells through the release of gammaAbu from interneurons. The net activity of Purkinje cells is related to their content of guanosine 3':5'-cyclic monophosphate (cGMP) which increases or decreases according to changes in the activity of climbing and mossy fibers as well as to changes in the activation of gammaAbu receptors. When these receptors are activated, the cGMP of Purkinje cells decreases; when they are inhibited, the cGMP increases.The cGMP content of the cerebellar cortex is altered by drugs that change either the excitatory input of climbing or mossy fibers or the inhibitory input mediated by the activation of gammaAbu receptors. Mechanisms by which various drugs alter the cerebellar content of cGMP were investigated. By using various experimental designs, it was shown that diazepam and muscimol lowered the cGMP content by activating gammaAbu receptors. In contrast, morphine and haloperidol lowered the cerebellar cortex cGMP by decreasing the excitation of mossy fibers whereas harmaline increased the cGMP by increasing the excitation of the climbing fibers.", "contents": "Mechanisms by which diazepam, muscimol, and other drugs change the content of cGMP in cerebellar cortex. THE CEREBELLUM CONSISTS OF TWO PARTS: the cerebellar nuclei whose connections to the various parts of the central nervous system coordinate muscle movements, and the cerebellar cortex which exerts an inhibitory influence on the cerebellar nuclei through the release of gamma-aminobutyric acid (gammaAbu) from Purkinje cells. The activity of Purkinje cells is regulated by two excitatory inputs to the cerebellar cortex-the climbing and mossy fibers-and by a neuronal network within the cortex which inhibits the activity of Purkinje cells through the release of gammaAbu from interneurons. The net activity of Purkinje cells is related to their content of guanosine 3':5'-cyclic monophosphate (cGMP) which increases or decreases according to changes in the activity of climbing and mossy fibers as well as to changes in the activation of gammaAbu receptors. When these receptors are activated, the cGMP of Purkinje cells decreases; when they are inhibited, the cGMP increases.The cGMP content of the cerebellar cortex is altered by drugs that change either the excitatory input of climbing or mossy fibers or the inhibitory input mediated by the activation of gammaAbu receptors. Mechanisms by which various drugs alter the cerebellar content of cGMP were investigated. By using various experimental designs, it was shown that diazepam and muscimol lowered the cGMP content by activating gammaAbu receptors. In contrast, morphine and haloperidol lowered the cerebellar cortex cGMP by decreasing the excitation of mossy fibers whereas harmaline increased the cGMP by increasing the excitation of the climbing fibers."}
{"id": "PMID:198793", "title": "31P nuclear magnetic resonance kinetic measurements on adenylatekinase.", "content": "By using 31P double-resonance nucelar magnetic resonance, preliminary kinetic measurements were made on the equilibrium reaction 2ADP in equilibrium ATP +AMP catalyzed by adenylate kinase. The double-resonance method used consisted of selectively inverting the spin population in a particular chemical environment and observing the transfer of the inverted spin to another chemical environment. The chemical transfer time between AMP and ADP, free in solution, was proportional to the substrate-to-enzyme ratio, and a transfer rate of 95 mol of AMP/see per mol of enzyme was obtained. In the same series of experiments, the life-time of AMP in solution was determined from the extra broadening of its resonance line due to the active enzyme. This gave a rate 3.2 times faster than the overall transfer rate given above. From these rates and other nuclear magnetic resonance  measurements wehave calculated the individual rate constants between the ternary complexes, AMP-enzyme-ATP and ADP-enzyme-ADP. In addition, we obtained one of the ADP off-rates from this latter complex. The rates on the enzyme are approximately 1250 and 500mol/sec per mol of enzyme for the forward and reverse directions, respectively. The ADP has an off-rate of 450 sec (-1).", "contents": "31P nuclear magnetic resonance kinetic measurements on adenylatekinase. By using 31P double-resonance nucelar magnetic resonance, preliminary kinetic measurements were made on the equilibrium reaction 2ADP in equilibrium ATP +AMP catalyzed by adenylate kinase. The double-resonance method used consisted of selectively inverting the spin population in a particular chemical environment and observing the transfer of the inverted spin to another chemical environment. The chemical transfer time between AMP and ADP, free in solution, was proportional to the substrate-to-enzyme ratio, and a transfer rate of 95 mol of AMP/see per mol of enzyme was obtained. In the same series of experiments, the life-time of AMP in solution was determined from the extra broadening of its resonance line due to the active enzyme. This gave a rate 3.2 times faster than the overall transfer rate given above. From these rates and other nuclear magnetic resonance  measurements wehave calculated the individual rate constants between the ternary complexes, AMP-enzyme-ATP and ADP-enzyme-ADP. In addition, we obtained one of the ADP off-rates from this latter complex. The rates on the enzyme are approximately 1250 and 500mol/sec per mol of enzyme for the forward and reverse directions, respectively. The ADP has an off-rate of 450 sec (-1)."}
{"id": "PMID:198794", "title": "Coupling in cytochrome c oxidase.", "content": "Cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase; EC 1.9.3.1) can be resolved into an electron transfer complex (ETC) and an ionophore transfer complex (ITC). Coupling requires an interaction between the moving electron in the ETC and a moving, positively charged ionophore-cation adduct in the ITC. The duplex character of cytochrome oxidase facilitates this interaction. The ITC mediates cyclical cation transport. It can be replaced as the coupling partner by the combination of valinomycin and nigericin in the presence of K(+) when cytochrome oxidase is incorporated into liposomes containing acidic phospholipids or by the combination of lipid cytochrome c and bile acids in an ITC-resolved preparation of the ETC. Respiratory control can be induced by incorporating cytochrome oxidase into vesicles of unfractionated whole mitochondrial lipid. The activity of the ITC is suppressed by such incorporation and this suppression leads to the emergence of respiratory control. The ionophoroproteins of the ITC can be extracted into organic solvents; some 50% of the total protein of cytochrome oxidase is extractable. The release of free ionophore is achieved by tryptic digestion of the ionophoroprotein. Preliminary to this release the ionophoroprotein is degraded to an ionophoropeptide. Electrogenic ionophores, as well as uncoupler, are liberated by such proteolysis. The ITC contains a set of ionophoroproteins imbedded in a matrix of phospholipid.", "contents": "Coupling in cytochrome c oxidase. Cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase; EC 1.9.3.1) can be resolved into an electron transfer complex (ETC) and an ionophore transfer complex (ITC). Coupling requires an interaction between the moving electron in the ETC and a moving, positively charged ionophore-cation adduct in the ITC. The duplex character of cytochrome oxidase facilitates this interaction. The ITC mediates cyclical cation transport. It can be replaced as the coupling partner by the combination of valinomycin and nigericin in the presence of K(+) when cytochrome oxidase is incorporated into liposomes containing acidic phospholipids or by the combination of lipid cytochrome c and bile acids in an ITC-resolved preparation of the ETC. Respiratory control can be induced by incorporating cytochrome oxidase into vesicles of unfractionated whole mitochondrial lipid. The activity of the ITC is suppressed by such incorporation and this suppression leads to the emergence of respiratory control. The ionophoroproteins of the ITC can be extracted into organic solvents; some 50% of the total protein of cytochrome oxidase is extractable. The release of free ionophore is achieved by tryptic digestion of the ionophoroprotein. Preliminary to this release the ionophoroprotein is degraded to an ionophoropeptide. Electrogenic ionophores, as well as uncoupler, are liberated by such proteolysis. The ITC contains a set of ionophoroproteins imbedded in a matrix of phospholipid."}
{"id": "PMID:198795", "title": "Nucleotide sequences of ribosome recgonition sites in messenger RNAs of vesicular stomatitis virus.", "content": "The ribosome recognition sites from vesicular stomatitis virus mRNAs have been isolated by ribosome protection of the mixture of viral mRNAs followed by complete separation of the protected sites by two-dimensional gel electrophoresis. The sites from the four major mRNAs each contain a single AUG initiation codon, indicating that they are true initiation sites, and the complete sequences of the N, NS, and G mRNA sites are reported. The sites do not all share common features nor do they have significant regions complementary to the known sequence at the 3'-terminus of 18S rRNA. The N and NS mRNAs show anine-nucleotide homology in the first eleven nucleotides extending from the capped 5'-end.", "contents": "Nucleotide sequences of ribosome recgonition sites in messenger RNAs of vesicular stomatitis virus. The ribosome recognition sites from vesicular stomatitis virus mRNAs have been isolated by ribosome protection of the mixture of viral mRNAs followed by complete separation of the protected sites by two-dimensional gel electrophoresis. The sites from the four major mRNAs each contain a single AUG initiation codon, indicating that they are true initiation sites, and the complete sequences of the N, NS, and G mRNA sites are reported. The sites do not all share common features nor do they have significant regions complementary to the known sequence at the 3'-terminus of 18S rRNA. The N and NS mRNAs show anine-nucleotide homology in the first eleven nucleotides extending from the capped 5'-end."}
{"id": "PMID:198796", "title": "Poliovirus-specific primer-dependent RNA polymerase able to copy poly(A).", "content": "A template-dependent RNA polymerase has been isolated from poliovirus-infected cells by assaying for the ability of the enzyme to copy poly(A) complexed to an oligo(U) primer. The polymerase was solubilized with detergent, and RNA was removed by precipitation with 2 M LiCl. The solubilized polymerase required both poly(A) and oligo(U) for activity and was stimulated by Mg2+ but was inhibited by Mn2+. Poly(A)-oligo(U)-dependent poly(U) polymerase was not found in extracts of HeLa cells until about 2 hr after poliovirus infection, and then there was a linear increase in activity until about 5 hr. Analysis of the polymerase by glycerol gradient centrifugation showed that the majority of the activity sedimented at about 4 S, indicating that it was no longer complexed with high-molecular-weight RNA or cellular membranes. This poly(A)-oligo(U)-dependent polymerase activity could represent an important component of the poliovirus RNA-dependent RNA polymerase.", "contents": "Poliovirus-specific primer-dependent RNA polymerase able to copy poly(A). A template-dependent RNA polymerase has been isolated from poliovirus-infected cells by assaying for the ability of the enzyme to copy poly(A) complexed to an oligo(U) primer. The polymerase was solubilized with detergent, and RNA was removed by precipitation with 2 M LiCl. The solubilized polymerase required both poly(A) and oligo(U) for activity and was stimulated by Mg2+ but was inhibited by Mn2+. Poly(A)-oligo(U)-dependent poly(U) polymerase was not found in extracts of HeLa cells until about 2 hr after poliovirus infection, and then there was a linear increase in activity until about 5 hr. Analysis of the polymerase by glycerol gradient centrifugation showed that the majority of the activity sedimented at about 4 S, indicating that it was no longer complexed with high-molecular-weight RNA or cellular membranes. This poly(A)-oligo(U)-dependent polymerase activity could represent an important component of the poliovirus RNA-dependent RNA polymerase."}
{"id": "PMID:198797", "title": "Novel mechanism for RNA maturation: the leader sequences of simian virus 40 mRNA are not transcribed adjacent to the coding sequences.", "content": "The 5'-terminal 100-200 ribonucleotides of late simian virus 40 (SV40) mRNAs are not transcribed immediately adjacent to their coding sequences. This conclusion is based on the following observations. The major late SV40 cytoplasmic RNA species, 16S and 19S, were purified from poly(A)-containing cytoplasmic RNA by hybridization to and elution from an SV40 DNA fragment that maps between 0.67 and 0.76. This fragment is remote from the DNA fragments that include the coding sequences. The RNA transcripts from the fragment located between 0.67 and 0.76 were found in abundance. Even though selected on oligo(dT)-cellulose columns, the 5'-terminal sequences did not contain poly(A) tails directly adjacent to their 3' termini. The 5' terminus of the 16S mRNA, as monitored by hybridization of the sequences adjacent to the \"cap\" structure, was found adjacent to the coding sequences when intact [3H]methyl-labeled RNA was hybridized with restriction fragments. However, after fragmentation, the methyl label of this same RNA hybridized with a fragment that is remote from the coding sequences and maps between 0.67 and 0.73. These results imply a novel mechanism for biosynthesis of SV40 mRNA.", "contents": "Novel mechanism for RNA maturation: the leader sequences of simian virus 40 mRNA are not transcribed adjacent to the coding sequences. The 5'-terminal 100-200 ribonucleotides of late simian virus 40 (SV40) mRNAs are not transcribed immediately adjacent to their coding sequences. This conclusion is based on the following observations. The major late SV40 cytoplasmic RNA species, 16S and 19S, were purified from poly(A)-containing cytoplasmic RNA by hybridization to and elution from an SV40 DNA fragment that maps between 0.67 and 0.76. This fragment is remote from the DNA fragments that include the coding sequences. The RNA transcripts from the fragment located between 0.67 and 0.76 were found in abundance. Even though selected on oligo(dT)-cellulose columns, the 5'-terminal sequences did not contain poly(A) tails directly adjacent to their 3' termini. The 5' terminus of the 16S mRNA, as monitored by hybridization of the sequences adjacent to the \"cap\" structure, was found adjacent to the coding sequences when intact [3H]methyl-labeled RNA was hybridized with restriction fragments. However, after fragmentation, the methyl label of this same RNA hybridized with a fragment that is remote from the coding sequences and maps between 0.67 and 0.73. These results imply a novel mechanism for biosynthesis of SV40 mRNA."}
{"id": "PMID:198798", "title": "Isolation of adenylate cyclase-free, beta-adrenergic receptor from turkey erythrocyte membranes by affinity chromatography.", "content": "The adenylate cyclase [ATP pyrophosphatelyase (cyclizing); EC 4.6.1.1] and beta-adrenergic receptor of plasma membranes of turkey erythrocytes were solubilized in an active form by treatment with either NaF or guanylylimidodiphosphate and digitonin. The solubilized enzyme was no longer stimulated by catecholamines, NaF, or guanine nucleotides. The digitonin extract was chromatographed on an alprenolol-agarose derivative. While the bulk of protein and all the adenylate cyclase activity passed unretarded through the column, the receptor was retained. It eluted free of enzyme activity with an alprenolol solution containing 1 M NaCl; the yield was 25-30%. The protein content of the alprenolol eluates was too low to be estimated by the Lowry technique and was assessed by a more sensitive fluorometric method. Under these conditions, the beta-adrenergic receptor was purified approximately 2000-fold in a single step with retention of all its pharmacological properties. These experiments establish that the beta-adrenergic receptor and the adenylate cyclase are independent entities which may be separated on a functional basis.", "contents": "Isolation of adenylate cyclase-free, beta-adrenergic receptor from turkey erythrocyte membranes by affinity chromatography. The adenylate cyclase [ATP pyrophosphatelyase (cyclizing); EC 4.6.1.1] and beta-adrenergic receptor of plasma membranes of turkey erythrocytes were solubilized in an active form by treatment with either NaF or guanylylimidodiphosphate and digitonin. The solubilized enzyme was no longer stimulated by catecholamines, NaF, or guanine nucleotides. The digitonin extract was chromatographed on an alprenolol-agarose derivative. While the bulk of protein and all the adenylate cyclase activity passed unretarded through the column, the receptor was retained. It eluted free of enzyme activity with an alprenolol solution containing 1 M NaCl; the yield was 25-30%. The protein content of the alprenolol eluates was too low to be estimated by the Lowry technique and was assessed by a more sensitive fluorometric method. Under these conditions, the beta-adrenergic receptor was purified approximately 2000-fold in a single step with retention of all its pharmacological properties. These experiments establish that the beta-adrenergic receptor and the adenylate cyclase are independent entities which may be separated on a functional basis."}
{"id": "PMID:198799", "title": "Reconstitution of catecholamine-sensitive adenylate cyclase activity: interactions of solubilized components with receptor-replete membranes.", "content": "Membranes of mouse L cells that contain adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] but lack beta-adrenergic receptors have been solubilized with Lubrol 12A9. Addition of such adenylate cyclase-containing extracts to beta-adrenergic receptor-replete membranes from adenylate cyclase-deficient S49 lymphoma cells results in the production of a catecholamine-sensitive adenylate cyclase system. The effects of beta-adrenergic agonists and antagonists on the reconstituted system reproduce those that are characteristic of the wild-type S49 lymphoma cell. The uncoupled variant of the S49lymphoma contains adenylate cyclase, but donor extracts from this clone fail to reconstitute the hormone-sensitive enzyme activity when added to adenylate cyclase-deficient membranes. Thus, the uncoupled and adenylate cyclase-deficient variants of the S49 cell are not complementary.", "contents": "Reconstitution of catecholamine-sensitive adenylate cyclase activity: interactions of solubilized components with receptor-replete membranes. Membranes of mouse L cells that contain adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] but lack beta-adrenergic receptors have been solubilized with Lubrol 12A9. Addition of such adenylate cyclase-containing extracts to beta-adrenergic receptor-replete membranes from adenylate cyclase-deficient S49 lymphoma cells results in the production of a catecholamine-sensitive adenylate cyclase system. The effects of beta-adrenergic agonists and antagonists on the reconstituted system reproduce those that are characteristic of the wild-type S49 lymphoma cell. The uncoupled variant of the S49lymphoma contains adenylate cyclase, but donor extracts from this clone fail to reconstitute the hormone-sensitive enzyme activity when added to adenylate cyclase-deficient membranes. Thus, the uncoupled and adenylate cyclase-deficient variants of the S49 cell are not complementary."}
{"id": "PMID:198800", "title": "Single-stranded DNA from oncornavirus-infected cells enriched in virus-specific DNA sequences.", "content": "We previously found that a minor fraction of single-stranded DNA (ss-DNA) isolated from native nuclear DNA of normal chicken embryonic cells and cells of other species hybridized with bulk nuclear DNA or cellular RNA in great excess. At least one-third of ss-DNA belonging to the nonrepetitious part of the cell genome could be hybridized to homologous RNAs. In the present work, similar results were obtained with ss-DNA from cells of chickens infected by avian myeloblastosis virus (AMV). To investigate whether this enrichment of ss-DNA in transcribed DNA sequences involves provirus DNA, radioactive AMV RNA and cDNA copies of AMV RNA were used. Most of the 70S AMV RNA hybridized much faster to ss-DNA from productively infected leukemic cells than to bulk DNA. cDNA, either double-stranded or single-stranded, made in the presence of actinomycin D hybridized to total nuclear DNA with similar kinetics. In contrast, about half of the double-stranded cDNA molecules hybridized 40-50 times faster to ss-DNA than to total DNA, indicating that only one of the provirus DNA strands seems to be present in ss-DNA. This was confirmed by the fact that relatively insignificant amounts of the ss-cDNA molecules made in the presence of actinomycin D could be annealed to ss-DNA as compared with bulk DNA. These results indicate that actively transcribed DNA sequences can be selectively distributed in the ss-DNA fraction, probably because of single strand breaks in the vicinity of transcription sites.", "contents": "Single-stranded DNA from oncornavirus-infected cells enriched in virus-specific DNA sequences. We previously found that a minor fraction of single-stranded DNA (ss-DNA) isolated from native nuclear DNA of normal chicken embryonic cells and cells of other species hybridized with bulk nuclear DNA or cellular RNA in great excess. At least one-third of ss-DNA belonging to the nonrepetitious part of the cell genome could be hybridized to homologous RNAs. In the present work, similar results were obtained with ss-DNA from cells of chickens infected by avian myeloblastosis virus (AMV). To investigate whether this enrichment of ss-DNA in transcribed DNA sequences involves provirus DNA, radioactive AMV RNA and cDNA copies of AMV RNA were used. Most of the 70S AMV RNA hybridized much faster to ss-DNA from productively infected leukemic cells than to bulk DNA. cDNA, either double-stranded or single-stranded, made in the presence of actinomycin D hybridized to total nuclear DNA with similar kinetics. In contrast, about half of the double-stranded cDNA molecules hybridized 40-50 times faster to ss-DNA than to total DNA, indicating that only one of the provirus DNA strands seems to be present in ss-DNA. This was confirmed by the fact that relatively insignificant amounts of the ss-cDNA molecules made in the presence of actinomycin D could be annealed to ss-DNA as compared with bulk DNA. These results indicate that actively transcribed DNA sequences can be selectively distributed in the ss-DNA fraction, probably because of single strand breaks in the vicinity of transcription sites."}
{"id": "PMID:198801", "title": "High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase.", "content": "A tumorigenic anchorage-dependent cell line (H-91) was established in culture from an azo-dye-induced rat ascites hepatoma. When grown in a glucose-containing medium the cells exhibit high rates of lactic acid production characteristic of rapidly growing tumor cells. However, when glucose is replaced with galactose the cells grow equally well but exhibit only moderately elevated rates of lactic acid production. The molecular basis for this observation cannot be attributed to differences in permeability because initial rates of glucose and galactose entry into hepatoma cells are identical. Rather, the activity of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is found to be high in hepatoma cells, about 20-fold higher than that of control and regenerating rat liver. Moreover, tumor hexokinase activity is not inhibited by low concentrations (<0.6 mM) of the reaction product glucose 6-phosphate. Additionally, 50% of the hexokinase activity of hepatoma cells is found associated with the mitochondrial fraction. This fraction is 3-fold enriched in hexokinase activity relative to the homogenate and 4-fold enriched relative to the nuclear and postmitochondrial fractions. Tumor mitochondrial hexokinase appears to be coupled directly to oxidative phosphorylation, because addition of glucose to respiring hepatoma mitochondria (after a burst of ATP synthesis) results in stimulation of respiration. In contrast, glucose has no effect on the respiration of mitochondria from control and regenerating liver. These results suggest that the high glycolytic capacity of H-91 hepatoma cells is due, at least in part, to an elevated form of hexokinase concentrated in the mitochondrial fraction of the cell.", "contents": "High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase. A tumorigenic anchorage-dependent cell line (H-91) was established in culture from an azo-dye-induced rat ascites hepatoma. When grown in a glucose-containing medium the cells exhibit high rates of lactic acid production characteristic of rapidly growing tumor cells. However, when glucose is replaced with galactose the cells grow equally well but exhibit only moderately elevated rates of lactic acid production. The molecular basis for this observation cannot be attributed to differences in permeability because initial rates of glucose and galactose entry into hepatoma cells are identical. Rather, the activity of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is found to be high in hepatoma cells, about 20-fold higher than that of control and regenerating rat liver. Moreover, tumor hexokinase activity is not inhibited by low concentrations (<0.6 mM) of the reaction product glucose 6-phosphate. Additionally, 50% of the hexokinase activity of hepatoma cells is found associated with the mitochondrial fraction. This fraction is 3-fold enriched in hexokinase activity relative to the homogenate and 4-fold enriched relative to the nuclear and postmitochondrial fractions. Tumor mitochondrial hexokinase appears to be coupled directly to oxidative phosphorylation, because addition of glucose to respiring hepatoma mitochondria (after a burst of ATP synthesis) results in stimulation of respiration. In contrast, glucose has no effect on the respiration of mitochondria from control and regenerating liver. These results suggest that the high glycolytic capacity of H-91 hepatoma cells is due, at least in part, to an elevated form of hexokinase concentrated in the mitochondrial fraction of the cell."}
{"id": "PMID:198802", "title": "Purification of simian virus 40 tumor antigen from a line of simian virus 40-transformed human cells.", "content": "Simian virus 40 tumor antigen can be isolated in a highly purified state from the nuclei ofSV80 cells, a continuous line of simian virus 40-transformed human fibroblasts. A five-step purification method was used. Its apparent molecular weight (in sodium dodecyl sulfate/polyacrylamide gels) is approximately 90,000-94,000. It contains a detectable amino-terminal residue.", "contents": "Purification of simian virus 40 tumor antigen from a line of simian virus 40-transformed human cells. Simian virus 40 tumor antigen can be isolated in a highly purified state from the nuclei ofSV80 cells, a continuous line of simian virus 40-transformed human fibroblasts. A five-step purification method was used. Its apparent molecular weight (in sodium dodecyl sulfate/polyacrylamide gels) is approximately 90,000-94,000. It contains a detectable amino-terminal residue."}
{"id": "PMID:198803", "title": "Enzyme regulation in neuroblastoma cells in a salts/glucose medium: induction of ornithine decarboxylase by asparagine and glutamine.", "content": "L-Asparagine is necessary and sufficient for the maximal induction of ornithine decarboxylase (ODC) (L-ornithine carboxy-lyase, EC 4.1.1.17) activity in confluent N18 mouse neuroblastoma cells in a salts/glucose medium; L-asparagine also induces maximal ODC activity when added to a tissue culture medium. L-Glutamine is about one-half as effective as asparagine. Cholera toxin and agents that are known to raise intracellular cyclic AMP concentrations have no effect on the induction of ODC activity unless suboptimal concentrations of asparagine are present in the salts/glucose medium. Whereas actinomycin D does not inhibit induction of ODC activity by asparagine, it inhibits the induction of ODC activity in association with cyclic AMP. In the salts/glucose medium, the rate of loss of ODC activity following the inhibition of protein synthesis by cycloheximide or puromycin depends upon the presence or absence of asparagine; loss is rapid only in the absence of asparagine and does not appear to be related to the inhibition of protein synthesis. These results are discussed in the context that the overlay of the growth medium tends to mask the minimal requirements for enzyme induction, because the composition of the medium defines: (a) the requirements for the induction of ODC activity; (b) the effect, or lack of effect, of cyclic AMP (and of inducers of intracellular cyclic AMP) on the induction of ODC activity; (c) the effect, or lack of effect, of actinomycin D on the induction of ODC activity; and (d) the action of puromycin and of cycloheximide on the rate of loss of ODC activity. It will be interesting to determine whether these results are uniquely applicable to ODC, whether many of the reactions attributed to cyclic AMP in the literature may be mediated by asparagine and glutamine, and whether actinomycin D, cycloheximide, and puromycin can be relied upon to differentiate between transcriptional and post-transcriptional control.", "contents": "Enzyme regulation in neuroblastoma cells in a salts/glucose medium: induction of ornithine decarboxylase by asparagine and glutamine. L-Asparagine is necessary and sufficient for the maximal induction of ornithine decarboxylase (ODC) (L-ornithine carboxy-lyase, EC 4.1.1.17) activity in confluent N18 mouse neuroblastoma cells in a salts/glucose medium; L-asparagine also induces maximal ODC activity when added to a tissue culture medium. L-Glutamine is about one-half as effective as asparagine. Cholera toxin and agents that are known to raise intracellular cyclic AMP concentrations have no effect on the induction of ODC activity unless suboptimal concentrations of asparagine are present in the salts/glucose medium. Whereas actinomycin D does not inhibit induction of ODC activity by asparagine, it inhibits the induction of ODC activity in association with cyclic AMP. In the salts/glucose medium, the rate of loss of ODC activity following the inhibition of protein synthesis by cycloheximide or puromycin depends upon the presence or absence of asparagine; loss is rapid only in the absence of asparagine and does not appear to be related to the inhibition of protein synthesis. These results are discussed in the context that the overlay of the growth medium tends to mask the minimal requirements for enzyme induction, because the composition of the medium defines: (a) the requirements for the induction of ODC activity; (b) the effect, or lack of effect, of cyclic AMP (and of inducers of intracellular cyclic AMP) on the induction of ODC activity; (c) the effect, or lack of effect, of actinomycin D on the induction of ODC activity; and (d) the action of puromycin and of cycloheximide on the rate of loss of ODC activity. It will be interesting to determine whether these results are uniquely applicable to ODC, whether many of the reactions attributed to cyclic AMP in the literature may be mediated by asparagine and glutamine, and whether actinomycin D, cycloheximide, and puromycin can be relied upon to differentiate between transcriptional and post-transcriptional control."}
{"id": "PMID:198804", "title": "Interaction of L-alpha-didecanoyl phosphatidylcholine with the AI polypeptide of high density lipoprotein.", "content": "Cooperative interaction of L-alpha-didecanoyl phosphatidylcholine with the AI polypeptide from human serum high density lipoprotein results in a complex particle containing 2 molecules of AI and 190 molecules of the lipid. Binding occurs two orders of magnitude above the critical micelle concentration of the lipid and requires the simultaneous presence of low levels of single-chain amphiphiles. The present investigation and previous studies from this laboratory suggest that AI contains \"pockets\" capable of interacting with a fixed hydrophobic volume and that amphiphilic head groups do not affect the binding capacity.", "contents": "Interaction of L-alpha-didecanoyl phosphatidylcholine with the AI polypeptide of high density lipoprotein. Cooperative interaction of L-alpha-didecanoyl phosphatidylcholine with the AI polypeptide from human serum high density lipoprotein results in a complex particle containing 2 molecules of AI and 190 molecules of the lipid. Binding occurs two orders of magnitude above the critical micelle concentration of the lipid and requires the simultaneous presence of low levels of single-chain amphiphiles. The present investigation and previous studies from this laboratory suggest that AI contains \"pockets\" capable of interacting with a fixed hydrophobic volume and that amphiphilic head groups do not affect the binding capacity."}
{"id": "PMID:198805", "title": "Strand breakage by the DNA untwisting enzyme results in covalent attachment of the enzyme to DNA.", "content": "Strands of DNA that have been broken by the DNA untwisting enzyme exhibit a reduced buoyant density in alkaline CsCl due to bound protein. A covalent linkage between the DNA and the enzyme was indicated by the stability of the complex in alkali (pH greaterthan 12.7), in 7 M guanidine-HCl, and at 90 degrees in 1% Sarkosyl for 5 min. The single-strand breaks generated by the enzyme are resistant to exonuclease III, indicating that the protein is attached to one of the ends of the broken strands. The free end of the broken strand bears a 5'-hydroxyl group, indicating attachment of the protein to the 3'-phosphoryl terminus. A nucleotide-peptide linkage involving a phosphoamide bond is unlikely since the complex is resistant to 3.5 M hydroxylamine at pH 4.75.", "contents": "Strand breakage by the DNA untwisting enzyme results in covalent attachment of the enzyme to DNA. Strands of DNA that have been broken by the DNA untwisting enzyme exhibit a reduced buoyant density in alkaline CsCl due to bound protein. A covalent linkage between the DNA and the enzyme was indicated by the stability of the complex in alkali (pH greaterthan 12.7), in 7 M guanidine-HCl, and at 90 degrees in 1% Sarkosyl for 5 min. The single-strand breaks generated by the enzyme are resistant to exonuclease III, indicating that the protein is attached to one of the ends of the broken strands. The free end of the broken strand bears a 5'-hydroxyl group, indicating attachment of the protein to the 3'-phosphoryl terminus. A nucleotide-peptide linkage involving a phosphoamide bond is unlikely since the complex is resistant to 3.5 M hydroxylamine at pH 4.75."}
{"id": "PMID:198806", "title": "Fundamental aspects of electron transfer: experimental verification of vibronically coupled electron tunneling.", "content": "A detailed investigation of the applicability of the vibronically coupled electron tunneling theory in biomolecules can be made by a quantitative study of a weak charge-transfer optical absorption band that has been predicted by this theory. The measurement of the position, width, and molar extinction coefficient of this band is examined in the bound model system cytochrome c-Fe(CN)6 at room temperature and demonstrates that the theory is quantitatively applicable in this system. The size of the parameters measured is typical of those relevant for biological electron transfers. The comparisons lend credibility to the generality of vibronically coupled electron theory in biomolecules and its short transfer distances.", "contents": "Fundamental aspects of electron transfer: experimental verification of vibronically coupled electron tunneling. A detailed investigation of the applicability of the vibronically coupled electron tunneling theory in biomolecules can be made by a quantitative study of a weak charge-transfer optical absorption band that has been predicted by this theory. The measurement of the position, width, and molar extinction coefficient of this band is examined in the bound model system cytochrome c-Fe(CN)6 at room temperature and demonstrates that the theory is quantitatively applicable in this system. The size of the parameters measured is typical of those relevant for biological electron transfers. The comparisons lend credibility to the generality of vibronically coupled electron theory in biomolecules and its short transfer distances."}
{"id": "PMID:198807", "title": "X-ray absorption edge studies on oxidized and reduced cytochrome c oxidase.", "content": "The x-ray absorption edge spectra of the Cu and Fe-centers in oxidized and reduced cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase: EC 1.9.3.1) have been obtained using synchrotron radiation from the SPEAR storage ring at the Stanford Linear Accelerator Center. In addition, oxidized and reduced plastocyanin as well as a number of model copper compounds in various oxidation states were also examined. A comparison of the absorption edge fine structure of cytochrome oxidase with those of the models indicates that one of the two coopers in the oxidized protein is in the +1 oxidation state. Upon reduction of the protein with dithionite, the second copper becomes Cu(I). The shift in the Fe K-edge of cytochrome oxidase upon reduction is small (about 2 e V or 3 times 10(-19 J) and is comparable to that previously observed for the reduction of the heme iron of cytochrome c.", "contents": "X-ray absorption edge studies on oxidized and reduced cytochrome c oxidase. The x-ray absorption edge spectra of the Cu and Fe-centers in oxidized and reduced cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase: EC 1.9.3.1) have been obtained using synchrotron radiation from the SPEAR storage ring at the Stanford Linear Accelerator Center. In addition, oxidized and reduced plastocyanin as well as a number of model copper compounds in various oxidation states were also examined. A comparison of the absorption edge fine structure of cytochrome oxidase with those of the models indicates that one of the two coopers in the oxidized protein is in the +1 oxidation state. Upon reduction of the protein with dithionite, the second copper becomes Cu(I). The shift in the Fe K-edge of cytochrome oxidase upon reduction is small (about 2 e V or 3 times 10(-19 J) and is comparable to that previously observed for the reduction of the heme iron of cytochrome c."}
{"id": "PMID:198808", "title": "Electron paramagentic resonance studies of photosynthetic electron transport: photoreduction of ferredoxinand membrane-bound iron-sulfur centers.", "content": "Electron paramagnetic resonance spectrometry was used to investigate, at physiological temperatures, light-induced electron transport from membrane-bound iron-sulfur components (bound ferredoxin) to soluble ferredoxin and NADP(+) in membrane fragments (from the blue-green alga, Nostoc muscorum) that had high rates of electron transport from water to NADP(+) and from an artificial electron donor, reduced dichlorophenolindophenol (DCIPH(2)) to NADP(+). Illumination at 20 degrees resulted in the photoreduction of membrane-bound iron-sulfur centers A and B. Photoreduction by water gave electron paramagnetic resonance signals of both centers A and B; photoreduction by DCIPH(2) was found to generate a strong electron paramagnetic signal of only center B. When water was the reductant, the addition and photoreduction of soluble ferredoxin generated additional signals characteristics of soluble ferredoxin without causing a decrease in the amplitude of the signals due to centers A and B. The further addition of NADP(+) (and its photoreduction) greatly diminished signals due to the bound iron-sulfur centers and to soluble ferredoxin. An outflow of electrons from center B to soluble ferredoxin and NADP(+) was particularly pronounced when DCIPH(2) was the reductant. These observations provide the first evidence for a light-induced electron transport between membrane-bound iron-sulfur centers and ferredoxin-NADP(+). The relationship of these observations to current concepts of photosynthetic electron transport is discussed.", "contents": "Electron paramagentic resonance studies of photosynthetic electron transport: photoreduction of ferredoxinand membrane-bound iron-sulfur centers. Electron paramagnetic resonance spectrometry was used to investigate, at physiological temperatures, light-induced electron transport from membrane-bound iron-sulfur components (bound ferredoxin) to soluble ferredoxin and NADP(+) in membrane fragments (from the blue-green alga, Nostoc muscorum) that had high rates of electron transport from water to NADP(+) and from an artificial electron donor, reduced dichlorophenolindophenol (DCIPH(2)) to NADP(+). Illumination at 20 degrees resulted in the photoreduction of membrane-bound iron-sulfur centers A and B. Photoreduction by water gave electron paramagnetic resonance signals of both centers A and B; photoreduction by DCIPH(2) was found to generate a strong electron paramagnetic signal of only center B. When water was the reductant, the addition and photoreduction of soluble ferredoxin generated additional signals characteristics of soluble ferredoxin without causing a decrease in the amplitude of the signals due to centers A and B. The further addition of NADP(+) (and its photoreduction) greatly diminished signals due to the bound iron-sulfur centers and to soluble ferredoxin. An outflow of electrons from center B to soluble ferredoxin and NADP(+) was particularly pronounced when DCIPH(2) was the reductant. These observations provide the first evidence for a light-induced electron transport between membrane-bound iron-sulfur centers and ferredoxin-NADP(+). The relationship of these observations to current concepts of photosynthetic electron transport is discussed."}
{"id": "PMID:198809", "title": "Glucose depletion accounts for the induction of two transformation-sensitive membrane proteinsin Rous sarcoma virus-transformed chick embryo fibroblasts.", "content": "Chick embryo fibroblasts transformed by Rous sarcoma virus have an increased content of two membrane proteins of molecular weights 78,000 and 95,000. The increased content of the 95,000-dalton protein and the principal increase in the content of the 78,000-dalton protein are not an early consequence of cell transformation but instead are secondary to the rapid depletion of glucose  from the growth medium of transformed cells. When glucose is maintained at high levels in the growth medium of transformed cells, the synthesis of the 95,000-dalton protein is arrested and that of the 78,000-dalton protein is markedly suppressed. Upon removal of glucose from the growth medium of normal cells, these proteins increase to levels comparable to those of transformed cells. Because the amount of these two proteins is influenced by the presence or absence of glucose, we suggest they be referred to as \"glucose-regulated proteins.\" GRP-78 and GRP-95. These proteins may have an important role in regulating the utilization of glucose in cultured cells.", "contents": "Glucose depletion accounts for the induction of two transformation-sensitive membrane proteinsin Rous sarcoma virus-transformed chick embryo fibroblasts. Chick embryo fibroblasts transformed by Rous sarcoma virus have an increased content of two membrane proteins of molecular weights 78,000 and 95,000. The increased content of the 95,000-dalton protein and the principal increase in the content of the 78,000-dalton protein are not an early consequence of cell transformation but instead are secondary to the rapid depletion of glucose  from the growth medium of transformed cells. When glucose is maintained at high levels in the growth medium of transformed cells, the synthesis of the 95,000-dalton protein is arrested and that of the 78,000-dalton protein is markedly suppressed. Upon removal of glucose from the growth medium of normal cells, these proteins increase to levels comparable to those of transformed cells. Because the amount of these two proteins is influenced by the presence or absence of glucose, we suggest they be referred to as \"glucose-regulated proteins.\" GRP-78 and GRP-95. These proteins may have an important role in regulating the utilization of glucose in cultured cells."}
{"id": "PMID:198810", "title": "Synthesis of collagen by chondrocytes in suspension culture: modulation by calcium, 3':5'-cyclic AMP, and prostaglandins.", "content": "Rabbit articular chondrocytes synthesize type II collagen [3alpha(1)(II)] in vivo and type I collagen [2alpha(1)(I).alpha(2)] in monolayer cultures. In suspension culture the nature of phenotype depends on extracellular Ca(2+). The relationship of Ca(2+) and 3':5'-cyclic AMP (cAMP) in regulation of collagen synthesis has been investigated. In suspension culture, cAMP levels of chondrocytes increase by 2- to 3-fold and then reach basal values regardless of the presence or absence of extracellular Ca(2+). The cells, however, synthesize primarily type II collagen in the absence of CaCl(2) in the medium and type I collagen in medium containing 1.8 mM CaCl(2). If CaCl(2) is added when intracellular cAMP levels are low, the phenotype is type I collagen. These observations minimize the role of cAMP as a second messenger in the chondrocyte culture system. Increasing endogenous cAMP with a phosphodiesterase inhibitor or adding exogenous dibutyryl-cAMP leads the cells to synthesize type I collagen, although this effect is significantly less pronounced if the medium contains ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). Increased concentrations of cAMP may mobilize the intracellular calcium pools and activate the cells to switch their phenotypic expression. Prostaglandins E(2) and F(2)alpha, thought to be involved in rheumatoid arthritis and bone resorption, have no significant effect on cAMP content of chondrocytes and alter their collagen phenotype to a small extent.", "contents": "Synthesis of collagen by chondrocytes in suspension culture: modulation by calcium, 3':5'-cyclic AMP, and prostaglandins. Rabbit articular chondrocytes synthesize type II collagen [3alpha(1)(II)] in vivo and type I collagen [2alpha(1)(I).alpha(2)] in monolayer cultures. In suspension culture the nature of phenotype depends on extracellular Ca(2+). The relationship of Ca(2+) and 3':5'-cyclic AMP (cAMP) in regulation of collagen synthesis has been investigated. In suspension culture, cAMP levels of chondrocytes increase by 2- to 3-fold and then reach basal values regardless of the presence or absence of extracellular Ca(2+). The cells, however, synthesize primarily type II collagen in the absence of CaCl(2) in the medium and type I collagen in medium containing 1.8 mM CaCl(2). If CaCl(2) is added when intracellular cAMP levels are low, the phenotype is type I collagen. These observations minimize the role of cAMP as a second messenger in the chondrocyte culture system. Increasing endogenous cAMP with a phosphodiesterase inhibitor or adding exogenous dibutyryl-cAMP leads the cells to synthesize type I collagen, although this effect is significantly less pronounced if the medium contains ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). Increased concentrations of cAMP may mobilize the intracellular calcium pools and activate the cells to switch their phenotypic expression. Prostaglandins E(2) and F(2)alpha, thought to be involved in rheumatoid arthritis and bone resorption, have no significant effect on cAMP content of chondrocytes and alter their collagen phenotype to a small extent."}
{"id": "PMID:198811", "title": "Division of BALB/c mouse 3T3 and simian virus 40-transformed 3T3 cells in cellular aggregates.", "content": "BALB/c mouse 3T3 cells and 3T3 cells transformed by simian virus 40 (SV40) were cultured as aggregates in agitated liquid medium. When maintained with daily medium changes, 3T3 cells incorporated [(3)H]thymidine into acid-insoluble material at a rate (1/4) that of 3T3 cells in logarithmic-phase flat cultures but 16 times that of the same cells in stationary-phase flat cultures. Similarly, SV40-transformed 3T3 cells in aggregates incorporated [(3)H]thymidine at (1/3) the rate of SV40-3T3 cells in logarithimic-phase flat culture and 14 times that of these cells in stationary-phase flat culture. Autoradiographs of aggregates of 3T3 and SV40-3T3 cells incubated for 2 hr in the presence of [(3)H]uridine and [(3)H]thymidine indicated that penetration of the nucleosides into aggregates during this period was limited to the outer four to six cell layers. Aggregates were also incubated in the presence of radiolabeled thymidine and uridine continuously for 4 days. Under these conditions, where nucleoside penetration was not limiting, 100% of the SV40-3T3 cells and 56% of the 3T3 cells incorporated [(3)H]thymidine into acid-insoluble material. The rates of cell division, cell loss, and net cell accumulation in aggregates of 3T3 and SV40-3T3 cells were measured by techniques not influenced by possible alterations in transport, pool size, or penetration. SV40-3T3 cells divided with a doubling time for the total population of 26.0 hr. The total cell number increased more slowly (doubling time of 48.3 hr) because of cell loss, which occurred with a half-time (time for 50% of the cells to be lost) of 53.3 hr. 3T3 cells in aggregates began to divide only after 3 days, then did so with a doubling time for the total population of 76.4 hr. Total cell number decreased (half-time of 26.3 hr) because this rate of cell division was exceeded by the rate of cell loss, which was constant with a half-time of 22.9 hr. The results suggest that 3T3 and SV40-3T3 cells display growth properties in aggregates consistent with their previously reported behavior in conventional flat culture: SV40-transformed 3T3 cells can proliferate under conditions of high cell density to a much greater extent than 3T3 cells can. Both cell lines, however, display an increased capacity to divide in aggregates relative to confluent flat culture, despite conditions of high cell density and absence of anchorage to an artificial solid substrate.", "contents": "Division of BALB/c mouse 3T3 and simian virus 40-transformed 3T3 cells in cellular aggregates. BALB/c mouse 3T3 cells and 3T3 cells transformed by simian virus 40 (SV40) were cultured as aggregates in agitated liquid medium. When maintained with daily medium changes, 3T3 cells incorporated [(3)H]thymidine into acid-insoluble material at a rate (1/4) that of 3T3 cells in logarithmic-phase flat cultures but 16 times that of the same cells in stationary-phase flat cultures. Similarly, SV40-transformed 3T3 cells in aggregates incorporated [(3)H]thymidine at (1/3) the rate of SV40-3T3 cells in logarithimic-phase flat culture and 14 times that of these cells in stationary-phase flat culture. Autoradiographs of aggregates of 3T3 and SV40-3T3 cells incubated for 2 hr in the presence of [(3)H]uridine and [(3)H]thymidine indicated that penetration of the nucleosides into aggregates during this period was limited to the outer four to six cell layers. Aggregates were also incubated in the presence of radiolabeled thymidine and uridine continuously for 4 days. Under these conditions, where nucleoside penetration was not limiting, 100% of the SV40-3T3 cells and 56% of the 3T3 cells incorporated [(3)H]thymidine into acid-insoluble material. The rates of cell division, cell loss, and net cell accumulation in aggregates of 3T3 and SV40-3T3 cells were measured by techniques not influenced by possible alterations in transport, pool size, or penetration. SV40-3T3 cells divided with a doubling time for the total population of 26.0 hr. The total cell number increased more slowly (doubling time of 48.3 hr) because of cell loss, which occurred with a half-time (time for 50% of the cells to be lost) of 53.3 hr. 3T3 cells in aggregates began to divide only after 3 days, then did so with a doubling time for the total population of 76.4 hr. Total cell number decreased (half-time of 26.3 hr) because this rate of cell division was exceeded by the rate of cell loss, which was constant with a half-time of 22.9 hr. The results suggest that 3T3 and SV40-3T3 cells display growth properties in aggregates consistent with their previously reported behavior in conventional flat culture: SV40-transformed 3T3 cells can proliferate under conditions of high cell density to a much greater extent than 3T3 cells can. Both cell lines, however, display an increased capacity to divide in aggregates relative to confluent flat culture, despite conditions of high cell density and absence of anchorage to an artificial solid substrate."}
{"id": "PMID:198812", "title": "Cell fusion induced by herpes simplex virus is promoted and suppressed by different viral glycoproteins.", "content": "Some of the factors that regulate membrane fusion resulting in polykaryocyte formationhave been investigated, using the model system of human cells infected with mutants of herpes simplex virus (HSV). One of the mutant viruses used in this study (MP) failed to produce the viral glycoprotein designated C2--a nonlethal defect that has previously been correlated with the polykaryocyte-inducing phenotype of this and other mutant strains (wild-type strains of HSV usually induce the aggregation of infected cells rather than their fusion). The other mutant virus (tsB5), a temperature-sensitive conditional-lethal mutant, failed to produce glycoprotein B2 at non-permissive temperature, whereas the synthesis of all other viral products appeared to be normal. We produced and isolated seven recombinants of MP and tsB5 that expressed both of the parental alterations in glycoprotein synthesis. All of the re-combinant viruses induced the fusion of infected cells at 34 degrees (correlated with the absence of C2 expression) but were unable to cause cell fusion at 39 degrees (correlated with the absence of C2 and of B2 expression), even after infection at multiplicities high enough to ensure that all cells in the cultures synthesized viral macromolecules. These results and studies on the dominance or recessiveness of the fusion-inducing phenotype in mixed infections provide evidence that glycoprotein B2 plays a critical role in the promotion of cell fusion and that glycoprotein C2 can act to suppress fusion.", "contents": "Cell fusion induced by herpes simplex virus is promoted and suppressed by different viral glycoproteins. Some of the factors that regulate membrane fusion resulting in polykaryocyte formationhave been investigated, using the model system of human cells infected with mutants of herpes simplex virus (HSV). One of the mutant viruses used in this study (MP) failed to produce the viral glycoprotein designated C2--a nonlethal defect that has previously been correlated with the polykaryocyte-inducing phenotype of this and other mutant strains (wild-type strains of HSV usually induce the aggregation of infected cells rather than their fusion). The other mutant virus (tsB5), a temperature-sensitive conditional-lethal mutant, failed to produce glycoprotein B2 at non-permissive temperature, whereas the synthesis of all other viral products appeared to be normal. We produced and isolated seven recombinants of MP and tsB5 that expressed both of the parental alterations in glycoprotein synthesis. All of the re-combinant viruses induced the fusion of infected cells at 34 degrees (correlated with the absence of C2 expression) but were unable to cause cell fusion at 39 degrees (correlated with the absence of C2 and of B2 expression), even after infection at multiplicities high enough to ensure that all cells in the cultures synthesized viral macromolecules. These results and studies on the dominance or recessiveness of the fusion-inducing phenotype in mixed infections provide evidence that glycoprotein B2 plays a critical role in the promotion of cell fusion and that glycoprotein C2 can act to suppress fusion."}
{"id": "PMID:198813", "title": "Amyloid protein SAA is associated with high density lipoprotein from human serum.", "content": "Human serums contain a protein antigenically related to protein AA, the principal protein of a major class of amyloid substance. The serum antigen, SAA, occurs mainly in a high molecular weight form, 1 to 2 X 10(5). This work shows that the bulk of the SAA sediments at density 1.12 g/cm3 and floats at density 1.21 g/cm3, as does the high density lipoprotein HDL3. SAA is associated with the apolipoproteins ApoA-I and ApoA-II. The total cholesterol:total protein ratio of the fraction with density 1.12-1.21 g/cm3 is 0.2:1, consistent with that of SAA constituent of the HDL3 fraction into low molecular weight species of the order of 13,000. The quantity of SAA may vary from 0.1% or more of the total protein of HDL3.", "contents": "Amyloid protein SAA is associated with high density lipoprotein from human serum. Human serums contain a protein antigenically related to protein AA, the principal protein of a major class of amyloid substance. The serum antigen, SAA, occurs mainly in a high molecular weight form, 1 to 2 X 10(5). This work shows that the bulk of the SAA sediments at density 1.12 g/cm3 and floats at density 1.21 g/cm3, as does the high density lipoprotein HDL3. SAA is associated with the apolipoproteins ApoA-I and ApoA-II. The total cholesterol:total protein ratio of the fraction with density 1.12-1.21 g/cm3 is 0.2:1, consistent with that of SAA constituent of the HDL3 fraction into low molecular weight species of the order of 13,000. The quantity of SAA may vary from 0.1% or more of the total protein of HDL3."}
{"id": "PMID:198814", "title": "Specific receptors for des-Asp1-angiotensin II ((\"angiotensin III\") in rat adrenals.", "content": "The specific binding of angiotensin II and des-Asp1-angiotensin II (\"angiotensin III\") III\") to rat adrenals was studied with the use of the tritiated peptides. The binding sites having maximal affinity for angiotensin II were characterized by an equilibrium dissociation constant of 3.3 to 5.2 X 10(-9) M. Angiotensin III was able to interact with these sites, and also with a class of sites with very high affinity, characterized by an equilibrium dissociation constant of 1 to 2 X 10(-10) M. These sites exhibited a greater affinity for the heptapeptide angiotensin III than for the octapeptide angiotensin II. These findings, together with the known potent aldosterone stimulating effect of angiotensin III and its presence in rat plasma, suggest that this heptapeptide could be the physiologically important steroidogenic angiotensin in this species.", "contents": "Specific receptors for des-Asp1-angiotensin II ((\"angiotensin III\") in rat adrenals. The specific binding of angiotensin II and des-Asp1-angiotensin II (\"angiotensin III\") III\") to rat adrenals was studied with the use of the tritiated peptides. The binding sites having maximal affinity for angiotensin II were characterized by an equilibrium dissociation constant of 3.3 to 5.2 X 10(-9) M. Angiotensin III was able to interact with these sites, and also with a class of sites with very high affinity, characterized by an equilibrium dissociation constant of 1 to 2 X 10(-10) M. These sites exhibited a greater affinity for the heptapeptide angiotensin III than for the octapeptide angiotensin II. These findings, together with the known potent aldosterone stimulating effect of angiotensin III and its presence in rat plasma, suggest that this heptapeptide could be the physiologically important steroidogenic angiotensin in this species."}
{"id": "PMID:198815", "title": "Alteration of cellular adhesion by nerve growth factor.", "content": "Nerve growth factor increases the initial rates of cell-substratum and cell-cell adhesion of sympathetic nerve cell clone PC12. It also stimulates adenosine 3':5'-cyclic monophosphate accumulation in the cells, and exogenous adenosine 3':5'-cyclic monophosphate increases cell-substratum adhesion. NGH-stimulated adhesion is energy dependent and cold-sensitive and does not require de novo protein synthesis. It is probably mediated by an effect of adenosine 3':5'-cyclic monophosphate on the plasma membrane. Stimulation of cellular adhesion may be the first step in NGF-initiated neurite outgrowth by sympathetic nerve cells.", "contents": "Alteration of cellular adhesion by nerve growth factor. Nerve growth factor increases the initial rates of cell-substratum and cell-cell adhesion of sympathetic nerve cell clone PC12. It also stimulates adenosine 3':5'-cyclic monophosphate accumulation in the cells, and exogenous adenosine 3':5'-cyclic monophosphate increases cell-substratum adhesion. NGH-stimulated adhesion is energy dependent and cold-sensitive and does not require de novo protein synthesis. It is probably mediated by an effect of adenosine 3':5'-cyclic monophosphate on the plasma membrane. Stimulation of cellular adhesion may be the first step in NGF-initiated neurite outgrowth by sympathetic nerve cells."}
{"id": "PMID:198838", "title": "Urinary cyclic AMP excretion by methadone subjects during gradual and acute withdrawal.", "content": "Laboratory and animal investigations have supported the hypothesis that levels of cyclic AMP are stable during tolerance to narcotic drugs and increased during withdrawal. In order to test this hypothesis, serial 24-h urinary excretion of cyclic AMP by long-term methadone addicts was determined during a period of stable methadone intake, a period of gradual withdrawal, and a period of acute withdrawal. Cyclic AMP excretion during stable methadone intake is identical to that of normal control subjects. Neither gradual nor acute withdrawal appears to affect the urinary excretion of cyclic AMP. These data agree with previous reports in the literature which suggest that cyclic AMP levels are not altered during tolerance to narcotics, but do not support the hypothesis that levels of the nucleotide might be increased during withdrawal.", "contents": "Urinary cyclic AMP excretion by methadone subjects during gradual and acute withdrawal. Laboratory and animal investigations have supported the hypothesis that levels of cyclic AMP are stable during tolerance to narcotic drugs and increased during withdrawal. In order to test this hypothesis, serial 24-h urinary excretion of cyclic AMP by long-term methadone addicts was determined during a period of stable methadone intake, a period of gradual withdrawal, and a period of acute withdrawal. Cyclic AMP excretion during stable methadone intake is identical to that of normal control subjects. Neither gradual nor acute withdrawal appears to affect the urinary excretion of cyclic AMP. These data agree with previous reports in the literature which suggest that cyclic AMP levels are not altered during tolerance to narcotics, but do not support the hypothesis that levels of the nucleotide might be increased during withdrawal."}
{"id": "PMID:198840", "title": "Effects on hypothalamic self-stimulation of drugs influencing dopaminergic neurotransmission injected into nucleus accumbens and corpus striatum of rats.", "content": "The role of the nucleus accumbens septi (ACB) and corpus striatum (CPU) in self-stimulation were investigated by injecting directly or indirectly acting stimulant drugs or a dopamine-(DA)-receptor blocking agent into each site bilaterally. d-Amphetamine (68 nmol) facilitated hypothalamic self-stimulation when injected into either side. Apomorphine (40 nmol) depressed or facilitated responding, the direction and magnitude of this effect being contingent (C = 0.52) on the effect of systemic injection (0.3 mg/kg.i.p.), and correlated with the difference between the effects of d- and l-amphetamine (0.5 mg/kg i.p.) but not with injection site. Haloperidol (6.6 nmol) in either site depressed self-stimulation. Tyramine (730 nmol), an agent believed to cause noncontingent displacement of transmitter from catecholamine terminals, depressed self-stimulation when injection into CPU, but facilitated it when injected into ACB. The site-specific effects found with tyramine but not with apomorphine may have been due to release by tyramine of transmitters other than DA.", "contents": "Effects on hypothalamic self-stimulation of drugs influencing dopaminergic neurotransmission injected into nucleus accumbens and corpus striatum of rats. The role of the nucleus accumbens septi (ACB) and corpus striatum (CPU) in self-stimulation were investigated by injecting directly or indirectly acting stimulant drugs or a dopamine-(DA)-receptor blocking agent into each site bilaterally. d-Amphetamine (68 nmol) facilitated hypothalamic self-stimulation when injected into either side. Apomorphine (40 nmol) depressed or facilitated responding, the direction and magnitude of this effect being contingent (C = 0.52) on the effect of systemic injection (0.3 mg/kg.i.p.), and correlated with the difference between the effects of d- and l-amphetamine (0.5 mg/kg i.p.) but not with injection site. Haloperidol (6.6 nmol) in either site depressed self-stimulation. Tyramine (730 nmol), an agent believed to cause noncontingent displacement of transmitter from catecholamine terminals, depressed self-stimulation when injection into CPU, but facilitated it when injected into ACB. The site-specific effects found with tyramine but not with apomorphine may have been due to release by tyramine of transmitters other than DA."}
{"id": "PMID:198844", "title": "Autosomal dominant osteosclerosis.", "content": "Two cases of a craniotubular hyperostosis are presented. The radiographic features closely resemble Van Buchem disease (hyperostosis corticalis generalisata; endosteal hyperostosis, recessive type), including symmetrical and bilateral diaphyseal cortical thickening of the long and short tubular bones as well as sclerosis and thickening of the calvaria, mandible, shoulder and pelvic girdles, and thoracic cage. Unlike Van Buchem disease, no periosteal excresences are observed, alkaline phosphatase is normal, no basal foramina encroachment of the skull is present, and the genetic pattern is dominant inheritance. These cases possibly represent a separate disorder rather than a variant of Van Buchem disease.", "contents": "Autosomal dominant osteosclerosis. Two cases of a craniotubular hyperostosis are presented. The radiographic features closely resemble Van Buchem disease (hyperostosis corticalis generalisata; endosteal hyperostosis, recessive type), including symmetrical and bilateral diaphyseal cortical thickening of the long and short tubular bones as well as sclerosis and thickening of the calvaria, mandible, shoulder and pelvic girdles, and thoracic cage. Unlike Van Buchem disease, no periosteal excresences are observed, alkaline phosphatase is normal, no basal foramina encroachment of the skull is present, and the genetic pattern is dominant inheritance. These cases possibly represent a separate disorder rather than a variant of Van Buchem disease."}
{"id": "PMID:198845", "title": "Generalized cortical hyperostosis (Van Buchem disease): nosologic considerations.", "content": "Six of 41 presumed cases of Van Buchem disease described in the literature fit uniform diagnostic criteria. Segregation analysis of these 6 cases, in addition to another the authors report, supports a recessive mode of inheritance. Genetic heterogeneity is confirmed by the demonstration of a dominantly-inherited phenotype resembling Van Buchem disease. The probable etiology is a defect in the endochrondral modulatory step regulating transformation of osteoclast to osteoblast.", "contents": "Generalized cortical hyperostosis (Van Buchem disease): nosologic considerations. Six of 41 presumed cases of Van Buchem disease described in the literature fit uniform diagnostic criteria. Segregation analysis of these 6 cases, in addition to another the authors report, supports a recessive mode of inheritance. Genetic heterogeneity is confirmed by the demonstration of a dominantly-inherited phenotype resembling Van Buchem disease. The probable etiology is a defect in the endochrondral modulatory step regulating transformation of osteoclast to osteoblast."}
{"id": "PMID:198846", "title": "Combination chemotherapy and radiotherapy in small-cell carcinoma of the lung.", "content": "A combination of chemotherapy (Cytoxan, vincristine, and CCNU) and radiation therapy was used to treat 37 patients with small-cell carcinoma of the lung. There was 49% complete remission and an overall 76% objective response with an overall median survival of 12.5 months and 17 months for those showing a complete response. No serious morbidity was observed.", "contents": "Combination chemotherapy and radiotherapy in small-cell carcinoma of the lung. A combination of chemotherapy (Cytoxan, vincristine, and CCNU) and radiation therapy was used to treat 37 patients with small-cell carcinoma of the lung. There was 49% complete remission and an overall 76% objective response with an overall median survival of 12.5 months and 17 months for those showing a complete response. No serious morbidity was observed."}
{"id": "PMID:198847", "title": "Autosomal dominant osteosclerosis.", "content": "Autosomal dominant osteosclerosis, an entity previously labelled by various names, is clearly separate from Van Buchem disease; Van Buchem disease exhibits autosomal recessive inheritance. The clinical manifestation of autosomal dominant osteosclerosis is a widened and deepened mandible with increased gonial angle. Radiographic manifestations include endosteal sclerosis of the neurocranium with loss of the diplo\u00eb, osteosclerosis and hyperostosis of the mandible with absence of the normal antegonial notches, endosteal sclerosis of the diaphyses of long bones (including metacarpals and metatarsals), and osteosclerosis of the pelvis.", "contents": "Autosomal dominant osteosclerosis. Autosomal dominant osteosclerosis, an entity previously labelled by various names, is clearly separate from Van Buchem disease; Van Buchem disease exhibits autosomal recessive inheritance. The clinical manifestation of autosomal dominant osteosclerosis is a widened and deepened mandible with increased gonial angle. Radiographic manifestations include endosteal sclerosis of the neurocranium with loss of the diplo\u00eb, osteosclerosis and hyperostosis of the mandible with absence of the normal antegonial notches, endosteal sclerosis of the diaphyses of long bones (including metacarpals and metatarsals), and osteosclerosis of the pelvis."}
{"id": "PMID:198851", "title": "Effects of prostaglandins on rat renal adenylate cyclase-cyclic AMP systems.", "content": "The effects of prostaglandin (PG) E1, E2, A1, F1alpha, F2alpha or D2 on the rat renal cortical, outer medullary and inner medullary adenylate cyclase-cyclic AMP systems were examined. While high concentrations (8X10-4M) of each prostaglandin stimulated adenylate cyclase activity in each area of the kidney, PGE1 was the only prostaglandin to stimulate at 10-7M. PGA's were the only prostaglandins tested besides PGE's which stimulated adenylate cyclase at less than 10-4M. This effect of PGA's was limited to the outer medulla. PGD2 was the least stimulatory. Observations with renal slices yielded qualitatively similar results. The PGE's were the most potent in each area with PGA's only stimulatory in the outer medulla. O2 deprivation (5% O2) lowered the slice cyclic AMP content in each area of the kidney. In the cortex and outer medulla, prostaglandin mediated increases in cyclic AMP content were either lower or absent at 5% O2 compared to 95% O2. However, in the inner medulla PGE stimulation was observed only at 5% O2 and not 95% O2. No other prostaglandins were found to increase inner medullary cyclic AMP content at 95% or 5% O2. These results illustrate that the adenylate cyclase-cyclic AMP system responds uniquely to prostaglandins in each area of the kidney. Consideration of these results along with correlative observations suggests that inner medullary produced PGE's may act as local modulators of inner medullary adenylate cyclase.", "contents": "Effects of prostaglandins on rat renal adenylate cyclase-cyclic AMP systems. The effects of prostaglandin (PG) E1, E2, A1, F1alpha, F2alpha or D2 on the rat renal cortical, outer medullary and inner medullary adenylate cyclase-cyclic AMP systems were examined. While high concentrations (8X10-4M) of each prostaglandin stimulated adenylate cyclase activity in each area of the kidney, PGE1 was the only prostaglandin to stimulate at 10-7M. PGA's were the only prostaglandins tested besides PGE's which stimulated adenylate cyclase at less than 10-4M. This effect of PGA's was limited to the outer medulla. PGD2 was the least stimulatory. Observations with renal slices yielded qualitatively similar results. The PGE's were the most potent in each area with PGA's only stimulatory in the outer medulla. O2 deprivation (5% O2) lowered the slice cyclic AMP content in each area of the kidney. In the cortex and outer medulla, prostaglandin mediated increases in cyclic AMP content were either lower or absent at 5% O2 compared to 95% O2. However, in the inner medulla PGE stimulation was observed only at 5% O2 and not 95% O2. No other prostaglandins were found to increase inner medullary cyclic AMP content at 95% or 5% O2. These results illustrate that the adenylate cyclase-cyclic AMP system responds uniquely to prostaglandins in each area of the kidney. Consideration of these results along with correlative observations suggests that inner medullary produced PGE's may act as local modulators of inner medullary adenylate cyclase."}
{"id": "PMID:198854", "title": "[\"E\" rosette formation in \"active\" T lymphocytes: phenomenon modulated by intracellular level of cyclic AMP and GMP (author's transl)].", "content": "The rosette formation envolving the binding of sheep red blood cells (SRBC) with active T lymphocytes was activated when the lymphocytes were incubated with levamisole, acetylcholine or carbamylcholine. Similar activation was seen when to the incubation medium was added substances of glucose metabolism (lactate, fumarate or succinate) or triphosphate de adenosina--ATP. The lymphocytes incubation with aminophyline, isoproterenol or 2-4-dinitrofenol--DNP--inhibited the rosette formation. The inhibition promoted by aminophyline was reversed by levamisole, acetylcholine or carbamylcholine, but not when lactate or ATP was used. When the rosette formation inhibition was caused by DNP, the reversion was only possible by ATP and no affect occurred if guanil cyclase activators were added to the incubation medium.", "contents": "[\"E\" rosette formation in \"active\" T lymphocytes: phenomenon modulated by intracellular level of cyclic AMP and GMP (author's transl)]. The rosette formation envolving the binding of sheep red blood cells (SRBC) with active T lymphocytes was activated when the lymphocytes were incubated with levamisole, acetylcholine or carbamylcholine. Similar activation was seen when to the incubation medium was added substances of glucose metabolism (lactate, fumarate or succinate) or triphosphate de adenosina--ATP. The lymphocytes incubation with aminophyline, isoproterenol or 2-4-dinitrofenol--DNP--inhibited the rosette formation. The inhibition promoted by aminophyline was reversed by levamisole, acetylcholine or carbamylcholine, but not when lactate or ATP was used. When the rosette formation inhibition was caused by DNP, the reversion was only possible by ATP and no affect occurred if guanil cyclase activators were added to the incubation medium."}
{"id": "PMID:198855", "title": "[Morphological (Macro-, micro-electronoptical) changes and cytoenzyme changes after ligation of the pulmonary artery, pulmonary veins and both in dogs].", "content": "In six dogs ligature of the main pulmonary artery was performed, and in five other ligature of the pulmonary veins was carried out, while in five other animals combined simultaneous ligatures were made. Extensive infarcization was noted, of the pulmonary tissue, with an evolution toward death, in all types of ligatures. Death occured earlier in ligatures of the pulmonary veins. All the interventions were performed on the left lung, under general anesthesia, orotracheal intubation and assisted respiration. Electron-optic investigation revealed mitochondrial alterations 30 minutes after ligature of the pulmonary veins and 2 hours after that of the pulmonary arteries. The lesions were extensive in time. In the infarction areas the activity of the energetic enzymes (SDH, NADH2, G6PD, LDM) appears to be reduced, and even completly abolished. This occurs earlier when pulmonary veins are closed. On the basis of clinical and surgical data already mentioned in the literature, as well as on that of the experimental studies performed, the authors consider that ligature of the pulmonary artery, either therapeutically or due to various necessities, an intervention that is recommended by some surgeons, is not a functional type of intervention, and can even have ill-fated results, especially if the pulmonary venous circulation is also involve in the pathological process.", "contents": "[Morphological (Macro-, micro-electronoptical) changes and cytoenzyme changes after ligation of the pulmonary artery, pulmonary veins and both in dogs]. In six dogs ligature of the main pulmonary artery was performed, and in five other ligature of the pulmonary veins was carried out, while in five other animals combined simultaneous ligatures were made. Extensive infarcization was noted, of the pulmonary tissue, with an evolution toward death, in all types of ligatures. Death occured earlier in ligatures of the pulmonary veins. All the interventions were performed on the left lung, under general anesthesia, orotracheal intubation and assisted respiration. Electron-optic investigation revealed mitochondrial alterations 30 minutes after ligature of the pulmonary veins and 2 hours after that of the pulmonary arteries. The lesions were extensive in time. In the infarction areas the activity of the energetic enzymes (SDH, NADH2, G6PD, LDM) appears to be reduced, and even completly abolished. This occurs earlier when pulmonary veins are closed. On the basis of clinical and surgical data already mentioned in the literature, as well as on that of the experimental studies performed, the authors consider that ligature of the pulmonary artery, either therapeutically or due to various necessities, an intervention that is recommended by some surgeons, is not a functional type of intervention, and can even have ill-fated results, especially if the pulmonary venous circulation is also involve in the pathological process."}
{"id": "PMID:198856", "title": "[Neurophysiological data on transmission and integration of nociceptive messages (author's transl)].", "content": "In this study cutaneous nociceptive messages are followed at different levels of the CNS, from the periphery to the cortex. A brief summary is given concerning the role of the fine myelinated and unmyelinated fibres which are specifically activated by noxious stimuli. A more extensive review considers the spinal mechanisms which sustain the transmission of nociceptive messages; the electrophysiological properties of interneurones located in laminae VIII, V, and I of the dorsal horn are described in detail. At the same time, the problem of the ascending projections of those cells activated by nociceptive stimuli is discussed. Particular attention is paid to the controls acting at the spinal level: segmental controls are described first and lead to discussion of the \"gate control theory\"; descending inhibitory controls are then discussed and their importance emphasized. The complexity of pain mechanisms at the supra-spinal level is underlined and a brief review considers the role of various bulbar, mesencephalic and thalamic structures involved in transmission of noxious messages. Among these structures, the PO group of nuclei seem to have a particular role in pain processes. Although the importance of the cortex for final integration of nociceptive messages is discussed, a brief summary is also given of investigations into the role of somatic area SII.", "contents": "[Neurophysiological data on transmission and integration of nociceptive messages (author's transl)]. In this study cutaneous nociceptive messages are followed at different levels of the CNS, from the periphery to the cortex. A brief summary is given concerning the role of the fine myelinated and unmyelinated fibres which are specifically activated by noxious stimuli. A more extensive review considers the spinal mechanisms which sustain the transmission of nociceptive messages; the electrophysiological properties of interneurones located in laminae VIII, V, and I of the dorsal horn are described in detail. At the same time, the problem of the ascending projections of those cells activated by nociceptive stimuli is discussed. Particular attention is paid to the controls acting at the spinal level: segmental controls are described first and lead to discussion of the \"gate control theory\"; descending inhibitory controls are then discussed and their importance emphasized. The complexity of pain mechanisms at the supra-spinal level is underlined and a brief review considers the role of various bulbar, mesencephalic and thalamic structures involved in transmission of noxious messages. Among these structures, the PO group of nuclei seem to have a particular role in pain processes. Although the importance of the cortex for final integration of nociceptive messages is discussed, a brief summary is also given of investigations into the role of somatic area SII."}
{"id": "PMID:198860", "title": "The agonist and antagonist properties of N-allylenkephalins.", "content": "The agonist (ID 50) and antagonist (Ke) potencies of the newly synthesized N-allyl derivatives of Met5-enkephalin and Leu5-enkephalin were compared with those of their respective parent compounds on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum. N-allyl substitution of the aminenitrogen in the Met5-enkephalin significantly decreased both the ID 50 and the Ke. In contrast, similar substitution in Leu5-enkephalin did not significantly alter the ID50, but caused an almost tenfold increase in the Ke. The results suggest that substitution on the amine-nitrogen of Leu5-enkephalin rather than Met5-enkephalin is more likely to produce potent narcotic antagonists.", "contents": "The agonist and antagonist properties of N-allylenkephalins. The agonist (ID 50) and antagonist (Ke) potencies of the newly synthesized N-allyl derivatives of Met5-enkephalin and Leu5-enkephalin were compared with those of their respective parent compounds on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum. N-allyl substitution of the aminenitrogen in the Met5-enkephalin significantly decreased both the ID 50 and the Ke. In contrast, similar substitution in Leu5-enkephalin did not significantly alter the ID50, but caused an almost tenfold increase in the Ke. The results suggest that substitution on the amine-nitrogen of Leu5-enkephalin rather than Met5-enkephalin is more likely to produce potent narcotic antagonists."}
{"id": "PMID:198861", "title": "An assessment of the effects of enzyme inducers on aryl hydrocarbon hydroxylase activity.", "content": "The aryl hydrocarbon hydroxylase activity for control, Aroclor 1254 and FireMaster BP-6 induced hepatic microsomes was determined using 4-chlorobiphenyl, a model PCB isomer, as the substrate. The assay system was used to quantitate the amount of metabolites, conjugates and macromolecular adducts formed for the induced and control microsomes. The metabolites and conjugates were designated detoxification (D) products and the macromolecular adducts designated as toxification (T) products. From the data it was then possible to determine a T/D index for each inducer and it is proposed that this index is useful in assessing the potential toxicity of microsomal enzyme inducers.", "contents": "An assessment of the effects of enzyme inducers on aryl hydrocarbon hydroxylase activity. The aryl hydrocarbon hydroxylase activity for control, Aroclor 1254 and FireMaster BP-6 induced hepatic microsomes was determined using 4-chlorobiphenyl, a model PCB isomer, as the substrate. The assay system was used to quantitate the amount of metabolites, conjugates and macromolecular adducts formed for the induced and control microsomes. The metabolites and conjugates were designated detoxification (D) products and the macromolecular adducts designated as toxification (T) products. From the data it was then possible to determine a T/D index for each inducer and it is proposed that this index is useful in assessing the potential toxicity of microsomal enzyme inducers."}
{"id": "PMID:198857", "title": "[Effects of aflatoxins B1 on glucose-6-phosphatase activity in kidney and liver of rats (Rattus rattus norvegicus)].", "content": "The authors observed the influence of the B1 aflatoxin over rat liver and kidneys glucose-6-phosphatase activity. Animals aged 30 and 60 days received B1 aflatoxin in oil, 1 mcg/g and 5 mcg/g of body weight. The parameters were observed 6, 24 and 48 hours after the micotoxin administration. There was significant decrease of glucemia in the 30 days animals. In the 60 days animals the results suggested possible increase in the liver glucose-6-phosphatase and marked decrease in glycogen.", "contents": "[Effects of aflatoxins B1 on glucose-6-phosphatase activity in kidney and liver of rats (Rattus rattus norvegicus)]. The authors observed the influence of the B1 aflatoxin over rat liver and kidneys glucose-6-phosphatase activity. Animals aged 30 and 60 days received B1 aflatoxin in oil, 1 mcg/g and 5 mcg/g of body weight. The parameters were observed 6, 24 and 48 hours after the micotoxin administration. There was significant decrease of glucemia in the 30 days animals. In the 60 days animals the results suggested possible increase in the liver glucose-6-phosphatase and marked decrease in glycogen."}
{"id": "PMID:198862", "title": "The airborne dispersal of foot-and-mouth disease virus from vaccinated and recovered pigs, cattle and sheep after exposure to infection.", "content": "Foot-and-mouth disease virus was detected during two periods in the air of looseboxes which housed susceptible, vaccinated or recovered pigs, cattle or sheep exposed to infection. The first was 30 min to 22 h after exposure and occurred in all animals. The second was two to seven days after exposure and occurred with those susceptible and vaccinated animals which developed clinical lesions, and with vaccinated and recovered pigs and sheep, which did not develop clinical lesions. Vaccination of animals before exposure resulted in less or no virus being detected. The virus during the first period was attributed to virus trapped on the animal during exposure, and the virus during the second period to limited multiplication in the respiratory tract. Control of movement for two weeks after contact with infection is suggested as a means of preventing spread of foot-and-mouth disease in areas that contain vaccinated animals.", "contents": "The airborne dispersal of foot-and-mouth disease virus from vaccinated and recovered pigs, cattle and sheep after exposure to infection. Foot-and-mouth disease virus was detected during two periods in the air of looseboxes which housed susceptible, vaccinated or recovered pigs, cattle or sheep exposed to infection. The first was 30 min to 22 h after exposure and occurred in all animals. The second was two to seven days after exposure and occurred with those susceptible and vaccinated animals which developed clinical lesions, and with vaccinated and recovered pigs and sheep, which did not develop clinical lesions. Vaccination of animals before exposure resulted in less or no virus being detected. The virus during the first period was attributed to virus trapped on the animal during exposure, and the virus during the second period to limited multiplication in the respiratory tract. Control of movement for two weeks after contact with infection is suggested as a means of preventing spread of foot-and-mouth disease in areas that contain vaccinated animals."}
{"id": "PMID:198867", "title": "[Lipids and beta-lipoproteins in hepatic cirrhosis].", "content": "The authors carried out a study of serum lipids and beta-lipoproteins using chemical methods commonly available in clinical pathological laboratories. The study was based on 72 men and women who were chemically and clinically healthy and 41 other patients with  biopsy confirmed hepatic cirrhosis, clinically decompensated. In cirrhotic patients there is a decrease in lipid and beta-lipoprotein values in serum. In plasma cirrhotics show a decrease in beta-lipoproteins. In addition the beta-lipoprotien molecule has a different make-up in cirrhotics which statistically is significantly altered from that seen in healthy patients. The graphic correlation between cholesterol, phospholipids and esterified fatty acids in serum as well as in beta-lipoproteins shows a different theoretical equation in the healty and cirrhotic patient. The beta-lipoproteins in cirrhotics are less atherogenic than the corresponding molecules in healthy individuals. The results here presented suggest that there is an important quantitative and qualitative alternation in lipid metabolism and in the biosynthesis of plasma lipoproteins in the uncontrolled cirrhotic.", "contents": "[Lipids and beta-lipoproteins in hepatic cirrhosis]. The authors carried out a study of serum lipids and beta-lipoproteins using chemical methods commonly available in clinical pathological laboratories. The study was based on 72 men and women who were chemically and clinically healthy and 41 other patients with  biopsy confirmed hepatic cirrhosis, clinically decompensated. In cirrhotic patients there is a decrease in lipid and beta-lipoprotein values in serum. In plasma cirrhotics show a decrease in beta-lipoproteins. In addition the beta-lipoprotien molecule has a different make-up in cirrhotics which statistically is significantly altered from that seen in healthy patients. The graphic correlation between cholesterol, phospholipids and esterified fatty acids in serum as well as in beta-lipoproteins shows a different theoretical equation in the healty and cirrhotic patient. The beta-lipoproteins in cirrhotics are less atherogenic than the corresponding molecules in healthy individuals. The results here presented suggest that there is an important quantitative and qualitative alternation in lipid metabolism and in the biosynthesis of plasma lipoproteins in the uncontrolled cirrhotic."}
{"id": "PMID:198872", "title": "[Primary maxillary location of myoblastoma].", "content": "The authors report the case of a myoblastoma with multiple successive and rare localisations: maxilla, cheek, lymphatics, lungs, liver and hyoid bone, with a fatal course over 28 months. They recall the possible malignancy of this tumour even in the absence of histological criteria and suggest its classification on bases which at present are only clinical.", "contents": "[Primary maxillary location of myoblastoma]. The authors report the case of a myoblastoma with multiple successive and rare localisations: maxilla, cheek, lymphatics, lungs, liver and hyoid bone, with a fatal course over 28 months. They recall the possible malignancy of this tumour even in the absence of histological criteria and suggest its classification on bases which at present are only clinical."}
{"id": "PMID:198873", "title": "Undernutrition and immunity: smallpox vaccination in chronically starved, undernourished subjects and its immunologic evaluation.", "content": "This study illustrates the specific immune response of chronically starved, undernourished adults after inoculation of live smallpox vaccine. It produced no adverse effect, and major vaccinial reaction was observed in all. 63% of undernourished individuals showed a fourfold or greater rise of the neutralizing antibody titre. In contrast, only 9% of normal healthy subjects could show similar response. However, the prevaccination titre was much lower in the undernourished group than in the control group, and the postvaccination titre also remained persistently lower in the former than in the latter group. Furthermore, whereas the specific humoral antibody response in the undernourished subjects was partially adequate, the development of specific cellular immunity against vaccinia was remarkably poor, indicating that smallpox vaccination in these subjects might be less effective against variola infection. This observed profound effect of chronic starvation and severe undernutrition on the immune apparatus was possibly multifactorial, protein depletion being the most important factor, as proved by the significantly low serum albumin level. The significantly low peripheral blood lymphocyte count and spectacular unresponsiveness to many antigens in these individuals suggested profound depression of the thymolymphatic system. Further, the significantly low level of neutralizing antibody in the malnourished subjects suggested that the formation of this protective antibody might necessitate the cooperation of T lymphocytes.", "contents": "Undernutrition and immunity: smallpox vaccination in chronically starved, undernourished subjects and its immunologic evaluation. This study illustrates the specific immune response of chronically starved, undernourished adults after inoculation of live smallpox vaccine. It produced no adverse effect, and major vaccinial reaction was observed in all. 63% of undernourished individuals showed a fourfold or greater rise of the neutralizing antibody titre. In contrast, only 9% of normal healthy subjects could show similar response. However, the prevaccination titre was much lower in the undernourished group than in the control group, and the postvaccination titre also remained persistently lower in the former than in the latter group. Furthermore, whereas the specific humoral antibody response in the undernourished subjects was partially adequate, the development of specific cellular immunity against vaccinia was remarkably poor, indicating that smallpox vaccination in these subjects might be less effective against variola infection. This observed profound effect of chronic starvation and severe undernutrition on the immune apparatus was possibly multifactorial, protein depletion being the most important factor, as proved by the significantly low serum albumin level. The significantly low peripheral blood lymphocyte count and spectacular unresponsiveness to many antigens in these individuals suggested profound depression of the thymolymphatic system. Further, the significantly low level of neutralizing antibody in the malnourished subjects suggested that the formation of this protective antibody might necessitate the cooperation of T lymphocytes."}
{"id": "PMID:198874", "title": "Human skeletal muscle in bacterial infection: enzyme activities and their relationship to age.", "content": "8 male patients (age 65-82 years) suffering from bacterial pneumonia or erysipelas were subjected to skeletal muscle biopsies. Significantly lower activities of lactate dehydrogenase (LDH) and glyceraldehyde-3-phosphate dehydrogenase (TPD) of skeletal muscle were recorded in the acute phase of the illness as compared to after the end of the convalescent phase. For citrate synthetase (CS) a similar although non-significant tendency was observed, while cytochrome c oxidase (CYTOX) was not altered by infection. Similar results have been reported in young patients with viral and mycoplasma infections. In the old patients the activity of LDH was approximately half of that found in the young patients (and in young controls confined to bed) on all occasions of measurement.", "contents": "Human skeletal muscle in bacterial infection: enzyme activities and their relationship to age. 8 male patients (age 65-82 years) suffering from bacterial pneumonia or erysipelas were subjected to skeletal muscle biopsies. Significantly lower activities of lactate dehydrogenase (LDH) and glyceraldehyde-3-phosphate dehydrogenase (TPD) of skeletal muscle were recorded in the acute phase of the illness as compared to after the end of the convalescent phase. For citrate synthetase (CS) a similar although non-significant tendency was observed, while cytochrome c oxidase (CYTOX) was not altered by infection. Similar results have been reported in young patients with viral and mycoplasma infections. In the old patients the activity of LDH was approximately half of that found in the young patients (and in young controls confined to bed) on all occasions of measurement."}
{"id": "PMID:198870", "title": "[Rheumatic manifestations of Gougerot-Houwers-Sj\u00f6gren syndrome].", "content": "The authors retrospectively survey the concept of the Gougerot-Houwers-5j\u00f6gren syndrome which links articular disease with the \"dry\" syndrome (pharyngitis sicca) and then go on to study the rheumatic conditions found in the Gougerot-Houwers-Sj\u00f6gren syndrome. They point out that the association between the \"dry\" syndrome and rheumatic appearances varies in frequency according as whether the problem is seen from a rheumatological, dermatological, ophthalmological or stomatological point of view. They establish the frequency of the various rheumatic conditions, stressing the importance of the association with rheumatoid polyarthritis. They study the associated biological and visceral backgrounds, the thyroid, renal, digestive, blood, neural, allergic and immunological conditions and describe the rheumatic appearances of the other collagenoses associated with the \"dry\" syndrome. They conclude with the current difficulty of restricting the scope of the Gougerot-Houwers-Sj\u00f6gren syndrome when histological and scintigraphic techniques have broadened it. They would like to see exact criteria adopted to define this syndrome.", "contents": "[Rheumatic manifestations of Gougerot-Houwers-Sj\u00f6gren syndrome]. The authors retrospectively survey the concept of the Gougerot-Houwers-5j\u00f6gren syndrome which links articular disease with the \"dry\" syndrome (pharyngitis sicca) and then go on to study the rheumatic conditions found in the Gougerot-Houwers-Sj\u00f6gren syndrome. They point out that the association between the \"dry\" syndrome and rheumatic appearances varies in frequency according as whether the problem is seen from a rheumatological, dermatological, ophthalmological or stomatological point of view. They establish the frequency of the various rheumatic conditions, stressing the importance of the association with rheumatoid polyarthritis. They study the associated biological and visceral backgrounds, the thyroid, renal, digestive, blood, neural, allergic and immunological conditions and describe the rheumatic appearances of the other collagenoses associated with the \"dry\" syndrome. They conclude with the current difficulty of restricting the scope of the Gougerot-Houwers-Sj\u00f6gren syndrome when histological and scintigraphic techniques have broadened it. They would like to see exact criteria adopted to define this syndrome."}
{"id": "PMID:198875", "title": "Haemophilus parainfluenzae infection of the central nervous system. A report on two infants.", "content": "Two cases of infection of the central nervous system (CNS) with Haemophilus parainfluenzae--a 12-month-old girl with meningitis and a 17-month-old girl with brain abscess--are reported. Both infants had long-standing upper respiratory infection before CNS disease. Both recovered after treatment.", "contents": "Haemophilus parainfluenzae infection of the central nervous system. A report on two infants. Two cases of infection of the central nervous system (CNS) with Haemophilus parainfluenzae--a 12-month-old girl with meningitis and a 17-month-old girl with brain abscess--are reported. Both infants had long-standing upper respiratory infection before CNS disease. Both recovered after treatment."}
{"id": "PMID:198876", "title": "Neuropathy and the automatic analysis of electromyographic signals from vibration exposed workers.", "content": "An automatic analysis of the electromyographic activity of the extensor digitorum communis, first dorsal interosseus and opponens pollicis muscles was performed, and both motor and sensory conduction velocities of the median and ulnar nerves were measured in the study of neuropathic changes that occur in traumatic vasospastic disease. Twenty-eight forest workers and 10 pneumatic-tool operators, all with a long occupational exposure to local vibration of the hands, were studied with these neurophysiological methods and general clinical and roentgenological examinations. Twenty male manual workers with a similar age distribution served as the comparison group. The most sensitive measures which separated the subjects with traumatic vasospastic disease from the nonexposed workers were the conduction velocity of the slower motor fibers of the ulnar nerve, the distal sensory conduction velocity and the motor distal latency of the median nerve. The duration and rise time of the averaged muscular potentials of intrinsic hand muscles correlated especially with those nerve conduction velocities which were the most sensitive in exhibiting neuropathic changes.", "contents": "Neuropathy and the automatic analysis of electromyographic signals from vibration exposed workers. An automatic analysis of the electromyographic activity of the extensor digitorum communis, first dorsal interosseus and opponens pollicis muscles was performed, and both motor and sensory conduction velocities of the median and ulnar nerves were measured in the study of neuropathic changes that occur in traumatic vasospastic disease. Twenty-eight forest workers and 10 pneumatic-tool operators, all with a long occupational exposure to local vibration of the hands, were studied with these neurophysiological methods and general clinical and roentgenological examinations. Twenty male manual workers with a similar age distribution served as the comparison group. The most sensitive measures which separated the subjects with traumatic vasospastic disease from the nonexposed workers were the conduction velocity of the slower motor fibers of the ulnar nerve, the distal sensory conduction velocity and the motor distal latency of the median nerve. The duration and rise time of the averaged muscular potentials of intrinsic hand muscles correlated especially with those nerve conduction velocities which were the most sensitive in exhibiting neuropathic changes."}
{"id": "PMID:198877", "title": "Hypertension: increase of collagen biosynthesis in arteries but not in veins.", "content": "In two models of hypertension in rats, it was shown that collagen synthesis and deposition are increased in arteries where blood pressure is elevated. By contrast, there were no alterations in any of the markers of collagen synthesis in veins, where blood pressure was only slightly elevated. It would appear that the stimulus for vascular collagen synthesis is provided by a direct effect of the increased pressure on the arterial cells rather than by a humoral factor released into the general circulation.", "contents": "Hypertension: increase of collagen biosynthesis in arteries but not in veins. In two models of hypertension in rats, it was shown that collagen synthesis and deposition are increased in arteries where blood pressure is elevated. By contrast, there were no alterations in any of the markers of collagen synthesis in veins, where blood pressure was only slightly elevated. It would appear that the stimulus for vascular collagen synthesis is provided by a direct effect of the increased pressure on the arterial cells rather than by a humoral factor released into the general circulation."}
{"id": "PMID:198878", "title": "Establishment of a cell line with associated Epstein-Barr-like virus from a leukemic orangutan.", "content": "An Epstein-Barr virus like herpesvirus has been isolated from a lymphoid cell line derived from an orangutan with spontaneous myelomonocytic leukemia. Herpesvirus has not previously been isolated from this species of higher ape.", "contents": "Establishment of a cell line with associated Epstein-Barr-like virus from a leukemic orangutan. An Epstein-Barr virus like herpesvirus has been isolated from a lymphoid cell line derived from an orangutan with spontaneous myelomonocytic leukemia. Herpesvirus has not previously been isolated from this species of higher ape."}
{"id": "PMID:198879", "title": "Adrenergic stimulation of taurine transport by the heart.", "content": "A high-affinity transport system that is specific for beta-amino acids has been delineated in rat hearts. This system transports the cardiotonic sulfonic amino acid taurine. beta-Adrenergic stimulation increases the transport capacity without effect on alpha-amino acid uptake, as does stimulation with adenosine 3',5'-monophosphate or theophylline. The existence of such an uptake system for taurine in the heart accounts for the high intra- to extracellular concentration gradient that is maintained, and suggests that cardiac stress is associated with increased taurine uptake. This may explain why taurine is the only amino acid to be markedly elevated in congestive heart failure. Taurine is a modifier of calcium fluxes in the heart, as are beta-adrenergic agonists. The presence of this uptake system suggests a link between beta-adrenergic stimulation of calcium and taurine fluxes.", "contents": "Adrenergic stimulation of taurine transport by the heart. A high-affinity transport system that is specific for beta-amino acids has been delineated in rat hearts. This system transports the cardiotonic sulfonic amino acid taurine. beta-Adrenergic stimulation increases the transport capacity without effect on alpha-amino acid uptake, as does stimulation with adenosine 3',5'-monophosphate or theophylline. The existence of such an uptake system for taurine in the heart accounts for the high intra- to extracellular concentration gradient that is maintained, and suggests that cardiac stress is associated with increased taurine uptake. This may explain why taurine is the only amino acid to be markedly elevated in congestive heart failure. Taurine is a modifier of calcium fluxes in the heart, as are beta-adrenergic agonists. The presence of this uptake system suggests a link between beta-adrenergic stimulation of calcium and taurine fluxes."}
{"id": "PMID:198880", "title": "[Hypercalcemia during acute intermittent porphyria. Apropos of 3 cases].", "content": "3 cases of hypercalcemia are reported, among 14 tetraplegic patients with porphyria. The calciuria, the estimations of parathormone, calcitonin and the isotopic calcium balance studies, suggested in the two most serious cases, hypercalcemia due to immobilisation. The main factor seems to be the duration of the immobilisation. The predisposing role of renal failure and catecholamines is discussed.", "contents": "[Hypercalcemia during acute intermittent porphyria. Apropos of 3 cases]. 3 cases of hypercalcemia are reported, among 14 tetraplegic patients with porphyria. The calciuria, the estimations of parathormone, calcitonin and the isotopic calcium balance studies, suggested in the two most serious cases, hypercalcemia due to immobilisation. The main factor seems to be the duration of the immobilisation. The predisposing role of renal failure and catecholamines is discussed."}
{"id": "PMID:198881", "title": "[Severe hypercalcemia during hyperthyroidism].", "content": "A particularly high hypercalcemia (141 mg/ml) was observed in a man with Graves' disease. An intense muscle asthenia, with lack of dynamism and vomiting which may cause dehydration, are the most suggestive signs of hypercalcemia. Bone biopsy and above all parathormone estimations permit one to eliminate associated hyperparathyroidism. The efficacy of mithramycin used alone, without any other hypocalcemic drug, was remarkable. The direct responsibility of thyrotoxicosis as a cause of the calcium disorder seems undoubted but the precise mechanism of the hypercalcemia remains unexplained.", "contents": "[Severe hypercalcemia during hyperthyroidism]. A particularly high hypercalcemia (141 mg/ml) was observed in a man with Graves' disease. An intense muscle asthenia, with lack of dynamism and vomiting which may cause dehydration, are the most suggestive signs of hypercalcemia. Bone biopsy and above all parathormone estimations permit one to eliminate associated hyperparathyroidism. The efficacy of mithramycin used alone, without any other hypocalcemic drug, was remarkable. The direct responsibility of thyrotoxicosis as a cause of the calcium disorder seems undoubted but the precise mechanism of the hypercalcemia remains unexplained."}
{"id": "PMID:198882", "title": "[Complication caused by abuse of alkalies in the treatment of ulcers].", "content": "The authors report the case of a 57 year old man who had taken for several years large quantities of alkaline drugs to relieve pain due to a gastric ulcer. This man presented acute digestive symptoms, and a confusional syndrome explained by various metabolic disturbance and especially hypercalcemia at 145 mg. Stopping the alkalis permitted within a few days the disappearance of the clinical symptoms and the correction of the laboratory disturbances. In the light of this case, the authors study the main clinical cases which have been described either in their acute form or in their chronic form (Burnett's syndrome). They discuss above all the physiopathology of these manifestations and it seems to them that the hypercalcemia is more important than the alkalosis. It remains to be explained why only a small number of subjects are exposed to these metabolic complications. There seems to be an individual hypersensitivity for under normal conditions, excess calcium is not sufficient to induce hypercalcemia.", "contents": "[Complication caused by abuse of alkalies in the treatment of ulcers]. The authors report the case of a 57 year old man who had taken for several years large quantities of alkaline drugs to relieve pain due to a gastric ulcer. This man presented acute digestive symptoms, and a confusional syndrome explained by various metabolic disturbance and especially hypercalcemia at 145 mg. Stopping the alkalis permitted within a few days the disappearance of the clinical symptoms and the correction of the laboratory disturbances. In the light of this case, the authors study the main clinical cases which have been described either in their acute form or in their chronic form (Burnett's syndrome). They discuss above all the physiopathology of these manifestations and it seems to them that the hypercalcemia is more important than the alkalosis. It remains to be explained why only a small number of subjects are exposed to these metabolic complications. There seems to be an individual hypersensitivity for under normal conditions, excess calcium is not sufficient to induce hypercalcemia."}
{"id": "PMID:198885", "title": "[Essential hypernatremia with hypovolemia caused by hypodipsia and partial diabetes insipidus].", "content": "The authors report the case of 13 year old girl presenting with chronic hypernatremia. This case should be considered as either neurogenic or essential hypernatremia. Partial diabetes insipidus and hypodipsia hypernatremia. Partial diabetes insipidus and hypodipsia are the cause of chronic hypovolemia and a new homeostasis with an exceptionally high level of sodium (isoosmotic point 154 mEq/l). No cause was found and in particular, the search for a cerebral disease was until now proved negative.", "contents": "[Essential hypernatremia with hypovolemia caused by hypodipsia and partial diabetes insipidus]. The authors report the case of 13 year old girl presenting with chronic hypernatremia. This case should be considered as either neurogenic or essential hypernatremia. Partial diabetes insipidus and hypodipsia hypernatremia. Partial diabetes insipidus and hypodipsia are the cause of chronic hypovolemia and a new homeostasis with an exceptionally high level of sodium (isoosmotic point 154 mEq/l). No cause was found and in particular, the search for a cerebral disease was until now proved negative."}
{"id": "PMID:198886", "title": "[Hyponatremia and myxedamatous coma].", "content": "The authors report a case of coma due to peripheral myxoedema with severe hyponatremia (111 mq) and low urinary sodium. The clinical and metabolic disorders regressed within ten days under treatment with thyroid. The frequency of hyponatremia during myxoedema coma is recalled and the pathogenic mechanism discussed. Although the adrenal origin seems excluded, there is possibly some hypervasopresinism, but it seems finally that the thyroxin-dependent hyponatremia is of renal origin.", "contents": "[Hyponatremia and myxedamatous coma]. The authors report a case of coma due to peripheral myxoedema with severe hyponatremia (111 mq) and low urinary sodium. The clinical and metabolic disorders regressed within ten days under treatment with thyroid. The frequency of hyponatremia during myxoedema coma is recalled and the pathogenic mechanism discussed. Although the adrenal origin seems excluded, there is possibly some hypervasopresinism, but it seems finally that the thyroxin-dependent hyponatremia is of renal origin."}
{"id": "PMID:198887", "title": "[Syndrome of inappropriate secretion of vasopressin. Apropos of 3 cases].", "content": "3 cases of inappropriate vasopressin secretion during one case of anaplastic carcinoma of the lung, one case of carcinoma of the prostate with bony metastases and one case of acute intermittent porphyria are presented. The plasma levels of vasopressin, measured by radioimmunoassay were high. Treatment with demeclocycline was attempted in one case. The clearance of free water was positive but the treatment was poorly tolerated by the digestive tract.", "contents": "[Syndrome of inappropriate secretion of vasopressin. Apropos of 3 cases]. 3 cases of inappropriate vasopressin secretion during one case of anaplastic carcinoma of the lung, one case of carcinoma of the prostate with bony metastases and one case of acute intermittent porphyria are presented. The plasma levels of vasopressin, measured by radioimmunoassay were high. Treatment with demeclocycline was attempted in one case. The clearance of free water was positive but the treatment was poorly tolerated by the digestive tract."}
{"id": "PMID:198888", "title": "[Striatal syndrome and hypokalemia].", "content": "The authors present the case of a patient with a striated syndrome resembling Wilson's disease but without the disorder of cooper metabolism. The clinical picture was completely masked by a hypokalemia at 1 mEq/l following urinary loss of this cation, due to ascending interstitial nephritis. Correction of the potassium deficiency produced rapid reappearance of the initial neurological syndrome.", "contents": "[Striatal syndrome and hypokalemia]. The authors present the case of a patient with a striated syndrome resembling Wilson's disease but without the disorder of cooper metabolism. The clinical picture was completely masked by a hypokalemia at 1 mEq/l following urinary loss of this cation, due to ascending interstitial nephritis. Correction of the potassium deficiency produced rapid reappearance of the initial neurological syndrome."}
{"id": "PMID:198889", "title": "[Hypokalemic familial periodic paralysis with basal electrocardiographic changes].", "content": "The authors report the case of an 18 year old girl with nocturnal tetraplegia. There was a family history of Westphal periodic paralysis, and a past history of transient paralysis two years previously. The serum potassium was 2.3 mEq/l. The patient was cured by intravenous drip of potassium chloride. There was a reactionary hyperinsulinism. The red cell potassium was lowered. There was a fall in the exchangeable and total potassium pool. The E.C.G. changes; observed during the acute attack of paralysis, persisted afterwards, which is unusual.", "contents": "[Hypokalemic familial periodic paralysis with basal electrocardiographic changes]. The authors report the case of an 18 year old girl with nocturnal tetraplegia. There was a family history of Westphal periodic paralysis, and a past history of transient paralysis two years previously. The serum potassium was 2.3 mEq/l. The patient was cured by intravenous drip of potassium chloride. There was a reactionary hyperinsulinism. The red cell potassium was lowered. There was a fall in the exchangeable and total potassium pool. The E.C.G. changes; observed during the acute attack of paralysis, persisted afterwards, which is unusual."}
{"id": "PMID:198890", "title": "[Paralysis with hypokalemia by transfer, treated by acetazolamide].", "content": "A case of familial paralysis with hypokalemia is presented. Acetazolamide at a dose of 500 mg daily prevents the onset of acute attacks. Under acetazolamide, an oral glucose tolerance test is not followed by hypokalemia. The association of glucose and insulin is unable to trigger off a paralytic attack although without acetazolamide, the same protocol had 5 months previously precipitated tetraplegia with hypokalemia. These results are compared with those in the literature.", "contents": "[Paralysis with hypokalemia by transfer, treated by acetazolamide]. A case of familial paralysis with hypokalemia is presented. Acetazolamide at a dose of 500 mg daily prevents the onset of acute attacks. Under acetazolamide, an oral glucose tolerance test is not followed by hypokalemia. The association of glucose and insulin is unable to trigger off a paralytic attack although without acetazolamide, the same protocol had 5 months previously precipitated tetraplegia with hypokalemia. These results are compared with those in the literature."}
{"id": "PMID:198892", "title": "[Hypokalemia and hypomagnesemia in a cirrhotic patient. Correction of metabolic disorders by magnesium].", "content": "The authors report the case of a cirrhotic with severe hypokalemia (2 mEq/l) responding incompletely to attempts at correction by classical treatments. The findings of a serum and red cell magnesium deficiency led to administration of this electrolyte which proved efficacous. They then recall the mechanism of hypokalemia and hypomagnesemia in alcoholics, study the possible relationship between these abnormalities, their noxious effects and suggest a treatment.", "contents": "[Hypokalemia and hypomagnesemia in a cirrhotic patient. Correction of metabolic disorders by magnesium]. The authors report the case of a cirrhotic with severe hypokalemia (2 mEq/l) responding incompletely to attempts at correction by classical treatments. The findings of a serum and red cell magnesium deficiency led to administration of this electrolyte which proved efficacous. They then recall the mechanism of hypokalemia and hypomagnesemia in alcoholics, study the possible relationship between these abnormalities, their noxious effects and suggest a treatment."}
{"id": "PMID:198893", "title": "[Bismuth treatment and blood bismuth levels].", "content": "The authors report the results of bismuth blood levels in 41 patients treated by oral route with bismuth salts used in gastro-enterology according to the Bensaude rule (10 to 20 g/day, 20 days/month). Median bismuth blood level during the period of treatment amounts to 13 microgram/l. It decreases to 7 microgram/l during the period of therapeutic withdrawal. In patients with bismuth encephalopathies (63 cases recorded in the literature) median values range from 680 to 700 microgram/l. The authors recommend the determination of bismuth blood levels as a monitoring method in bismuth treatment and propose the following values:--normal level during treatment : less than 50 microgram/l (in Bi metal);--alarm level : 50 to 100 microgram/l : (patients to be monitored);--toxicity level less than 100 microgram/l : (treatment to be interrupted).", "contents": "[Bismuth treatment and blood bismuth levels]. The authors report the results of bismuth blood levels in 41 patients treated by oral route with bismuth salts used in gastro-enterology according to the Bensaude rule (10 to 20 g/day, 20 days/month). Median bismuth blood level during the period of treatment amounts to 13 microgram/l. It decreases to 7 microgram/l during the period of therapeutic withdrawal. In patients with bismuth encephalopathies (63 cases recorded in the literature) median values range from 680 to 700 microgram/l. The authors recommend the determination of bismuth blood levels as a monitoring method in bismuth treatment and propose the following values:--normal level during treatment : less than 50 microgram/l (in Bi metal);--alarm level : 50 to 100 microgram/l : (patients to be monitored);--toxicity level less than 100 microgram/l : (treatment to be interrupted)."}
{"id": "PMID:198894", "title": "[Deceptive and revealing clinical forms of acute respiratory insufficience in chronic bronchopneumopathies].", "content": "The authors report 6 cases of acute respiratory failure complicating chronic bronchial and lung disease admitted to hospital with the diagnosis of: heart disease, 3 cases, pulmonary oedema, pulmonary embolism, atrial flutter; status asthmaticus : one case; neuro-psychiatric disease : 2 cases (toxic coma and agitation). The authors emphasize the frequency of chronic bronchial disease and recall the signs of acute decompensation discussing the possible difficulties in diagnosis and the therapeutic implications.", "contents": "[Deceptive and revealing clinical forms of acute respiratory insufficience in chronic bronchopneumopathies]. The authors report 6 cases of acute respiratory failure complicating chronic bronchial and lung disease admitted to hospital with the diagnosis of: heart disease, 3 cases, pulmonary oedema, pulmonary embolism, atrial flutter; status asthmaticus : one case; neuro-psychiatric disease : 2 cases (toxic coma and agitation). The authors emphasize the frequency of chronic bronchial disease and recall the signs of acute decompensation discussing the possible difficulties in diagnosis and the therapeutic implications."}
{"id": "PMID:198895", "title": "[Misleading pulmonary emboliu].", "content": "The authors report 12 cases of pulmonary embolism with misleading signs and discuss the difficulty in diagnosis: 1) the frequency of incomplete forms; 2) lack of specificity of the clinical and paraclinical picture of pulmonary embolism which may simulate pulmonary or heart disease; 3) difficulties in interpretation of the signs of pulmonary embolism in cases of prior heart or pulmonary disease.", "contents": "[Misleading pulmonary emboliu]. The authors report 12 cases of pulmonary embolism with misleading signs and discuss the difficulty in diagnosis: 1) the frequency of incomplete forms; 2) lack of specificity of the clinical and paraclinical picture of pulmonary embolism which may simulate pulmonary or heart disease; 3) difficulties in interpretation of the signs of pulmonary embolism in cases of prior heart or pulmonary disease."}
{"id": "PMID:198896", "title": "[Myotonic dystrophy and acute respiratory insufficiency].", "content": "Myotonic dystrophy or Steinert's disease may be discovered during acute respiratory failure, sometimes caused by a general anaesthetic. It complicates chronic respiratory failure which is present in almost all cases, both restrictive and obstructive, the clinical signs of which progress with the myopathy. Apart from myotonic degeneration of the respiratory muscles, a hypoventilation syndrome of central origin has been described, but the etiology of this respiratory failure is dominated by repeated aspiration pneumonia favoured by constant dysphagia and passage of food into the trachea and poor cough reflex. One should attempt to correct this.", "contents": "[Myotonic dystrophy and acute respiratory insufficiency]. Myotonic dystrophy or Steinert's disease may be discovered during acute respiratory failure, sometimes caused by a general anaesthetic. It complicates chronic respiratory failure which is present in almost all cases, both restrictive and obstructive, the clinical signs of which progress with the myopathy. Apart from myotonic degeneration of the respiratory muscles, a hypoventilation syndrome of central origin has been described, but the etiology of this respiratory failure is dominated by repeated aspiration pneumonia favoured by constant dysphagia and passage of food into the trachea and poor cough reflex. One should attempt to correct this."}
{"id": "PMID:198897", "title": "[HLA system and rhizomelic pseudopolyarthritis].", "content": "26 HLA antigens of the loci A and B were studied in 50 patients with pseudo-polyarthritis and in 300 control subjects without any joint disease. The arthritis was isolated and not associated with temporal arteritis. An increase in frequency of both HLA antigens was noted in the patients studied: HLA-B5 = 24% as against 13% in controls (P = 0.05 and Pc NS). HLA-Bw38 = 18% as against 5.33% in controls (p = 0.002 - Pc = o.05). The rise in frequency of HLA-B5 and HLA-Bw38 was also found in 19 subjects with polyarthritis and temporal arteritis but not in 31 patients with temporal arteritis alone. In this disease, a link with the HLA-B14 antigen was noted in 50 cases (22.9% as against 8.6% in control). These results suggest that arthritis and temporal arteritis although sometimes associated are probably distinct diseases.", "contents": "[HLA system and rhizomelic pseudopolyarthritis]. 26 HLA antigens of the loci A and B were studied in 50 patients with pseudo-polyarthritis and in 300 control subjects without any joint disease. The arthritis was isolated and not associated with temporal arteritis. An increase in frequency of both HLA antigens was noted in the patients studied: HLA-B5 = 24% as against 13% in controls (P = 0.05 and Pc NS). HLA-Bw38 = 18% as against 5.33% in controls (p = 0.002 - Pc = o.05). The rise in frequency of HLA-B5 and HLA-Bw38 was also found in 19 subjects with polyarthritis and temporal arteritis but not in 31 patients with temporal arteritis alone. In this disease, a link with the HLA-B14 antigen was noted in 50 cases (22.9% as against 8.6% in control). These results suggest that arthritis and temporal arteritis although sometimes associated are probably distinct diseases."}
{"id": "PMID:198898", "title": "[Hematological and clinical manifestations of bone marrow metastasis of carcinomas. Apropos of 36 cases verified by biopsy].", "content": "A retrospective study of 36 cases of bone marrow metastases from carcinoma is reported. In all cases, the presence of tumour cells was confirmed by needle biopsy of the bone marrow. The clinical picture was fairly typical: decline in general health, fever, bony pain and skin and mucosal hemorrhages. Radiological lesions of the skeleton were present in 64% of cases. Sometimes the blood disorders were isolated. Anemia was almost constant (86), normochromic, normocytic, and may be associated with leukocytosis and thrombopenia. Pancytopenia is rarer as also is a rise in the number of platelets. Erythremia, very suggestive, is demonstrated in 73% of the blood smears. In 31% of the slides examined again, schizocytes were found among the normal red cells. Disorders of hemostasis were easily circumscribed. As fibrinolysis was sometime found, hemostasis was studied as a routine in all patients. The special recruitment of a hematology unit explains the high frequency of blood abnormalities in this series of bone metastases.", "contents": "[Hematological and clinical manifestations of bone marrow metastasis of carcinomas. Apropos of 36 cases verified by biopsy]. A retrospective study of 36 cases of bone marrow metastases from carcinoma is reported. In all cases, the presence of tumour cells was confirmed by needle biopsy of the bone marrow. The clinical picture was fairly typical: decline in general health, fever, bony pain and skin and mucosal hemorrhages. Radiological lesions of the skeleton were present in 64% of cases. Sometimes the blood disorders were isolated. Anemia was almost constant (86), normochromic, normocytic, and may be associated with leukocytosis and thrombopenia. Pancytopenia is rarer as also is a rise in the number of platelets. Erythremia, very suggestive, is demonstrated in 73% of the blood smears. In 31% of the slides examined again, schizocytes were found among the normal red cells. Disorders of hemostasis were easily circumscribed. As fibrinolysis was sometime found, hemostasis was studied as a routine in all patients. The special recruitment of a hematology unit explains the high frequency of blood abnormalities in this series of bone metastases."}
{"id": "PMID:198899", "title": "[Parenteral feeding. Prevention of complications in adults during exclusive mid-term parenteral feeding].", "content": "The benefits of parenteral feeding need no longer be emphasised. However, qualitative and quantitative food supplements raise a certain number of difficulties which should be better known. Infection is the most frequent complication. It may be avoided by strict aseptic precautions throughout parenteral feeding. Hypoglycemia is a major risk owing to the possible consequence. Hyperglycemia and its consequence of osmotic polyuria is more frequent and should be controlled to avoid loss of water and salt. Complications due to the use of lipid emulsions are exceptional when soya oil is used. Hypophosphoremia should be corrected by increasing phosphate intake. Hypocalcemia is common; it is often associated with hypoproteinemia and sometime a low calcium intake, vitamin D deficiency or a sudden increase in phosphate intake. Vitamin deficiencies, hypomagnesemia, and oligo-element deficiencies should be correcty by appropriate supplements.", "contents": "[Parenteral feeding. Prevention of complications in adults during exclusive mid-term parenteral feeding]. The benefits of parenteral feeding need no longer be emphasised. However, qualitative and quantitative food supplements raise a certain number of difficulties which should be better known. Infection is the most frequent complication. It may be avoided by strict aseptic precautions throughout parenteral feeding. Hypoglycemia is a major risk owing to the possible consequence. Hyperglycemia and its consequence of osmotic polyuria is more frequent and should be controlled to avoid loss of water and salt. Complications due to the use of lipid emulsions are exceptional when soya oil is used. Hypophosphoremia should be corrected by increasing phosphate intake. Hypocalcemia is common; it is often associated with hypoproteinemia and sometime a low calcium intake, vitamin D deficiency or a sudden increase in phosphate intake. Vitamin deficiencies, hypomagnesemia, and oligo-element deficiencies should be correcty by appropriate supplements."}
{"id": "PMID:198911", "title": "The lipid disorders centre at the Transvaal Memorial Hospital for Children. A review of the first 30 months.", "content": "A specialized clinic for the investigation and treatment of familial lipoprotein disorders was started at the Transvaal Memorial Hospital for Children in July 1972. The reasons for its formation, its siting at a paediatric hospital and patient protocols are detailed. During the first 30 months, 195 patients with familial hyperlipoproteinaemia were seen. The ethnic distribution revealed a disproportionately high prevalence of lipoprotein disorders in the Afrikaner population. The most common lipoprotein disturbance seen was familial hypercholesterolaemia or Fredrickson type II hyperlipoproteinaemia, which was found in 84% of the patients. Included in this group were 18 homozygotes. The majority of patients were between 1 and 20 years, while few were over the age of 50. The incidence of ischaemic heart disease at various ages in the clinic population is reported. Results of therapy, both dietary and drug, for the various types of hyperlipoproteinaemia are presented. The contribution of familial hypercholesterolaemia to the high incidence of ischaemic heart disease and its possible implications in young White South Africans is discussed.", "contents": "The lipid disorders centre at the Transvaal Memorial Hospital for Children. A review of the first 30 months. A specialized clinic for the investigation and treatment of familial lipoprotein disorders was started at the Transvaal Memorial Hospital for Children in July 1972. The reasons for its formation, its siting at a paediatric hospital and patient protocols are detailed. During the first 30 months, 195 patients with familial hyperlipoproteinaemia were seen. The ethnic distribution revealed a disproportionately high prevalence of lipoprotein disorders in the Afrikaner population. The most common lipoprotein disturbance seen was familial hypercholesterolaemia or Fredrickson type II hyperlipoproteinaemia, which was found in 84% of the patients. Included in this group were 18 homozygotes. The majority of patients were between 1 and 20 years, while few were over the age of 50. The incidence of ischaemic heart disease at various ages in the clinic population is reported. Results of therapy, both dietary and drug, for the various types of hyperlipoproteinaemia are presented. The contribution of familial hypercholesterolaemia to the high incidence of ischaemic heart disease and its possible implications in young White South Africans is discussed."}
{"id": "PMID:198913", "title": "Comparison of lactate and pyruvate during endotoxic shock.", "content": "The livers of Sprague-Dawley rats, previously injected with endotoxin, were isolated and perfused in a controlled environment with known amounts of lactate or pyruvate. Samples were taken after one hour to determine substrate utilization, content of oxidized and reduced metabolites, adenylate energy charge and reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide + ratio. In this experiment, it was found that, in the group treated with endotoxin and perfused with lactate substrate, utilization and adenylate energy charge were reduced, while the concentration of reduced metabolites and reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide + ratio were increased. We conclude that infusion of lactate solutions to patients in a state of shock may have an adverse effect upon cellular function.", "contents": "Comparison of lactate and pyruvate during endotoxic shock. The livers of Sprague-Dawley rats, previously injected with endotoxin, were isolated and perfused in a controlled environment with known amounts of lactate or pyruvate. Samples were taken after one hour to determine substrate utilization, content of oxidized and reduced metabolites, adenylate energy charge and reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide + ratio. In this experiment, it was found that, in the group treated with endotoxin and perfused with lactate substrate, utilization and adenylate energy charge were reduced, while the concentration of reduced metabolites and reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide + ratio were increased. We conclude that infusion of lactate solutions to patients in a state of shock may have an adverse effect upon cellular function."}
{"id": "PMID:198914", "title": "Postresection stage grouping in carcinoma of the lung.", "content": "The postsurgical treatment classification and staging system for carcinoma of the lung has been evaluated in a series of 403 patients admitted to a completed prospective randomized adjuvant cancer chemotherapy trial conducted by the Veterans Administration Surgical Adjuvant Group. The proposed T, N and M classification suggested by the American Joint Committee for Cancer Staging and End Results Reporting is supported. However, the stage groupings as suggested by the Committee fails to separate adequately the various prognostic groups. This appears to be better accomplished by the stage grouping modification suggested by the Radiation Therapy Oncology Group. In the latter schema, the five year survival rate of patients with postsurgical treatment Stage I disease is 40.9 per cent; Stage II, 26.2 per cent, and Stage III, 10.5 per cent. In the Joint Committee classification, these survival rates are 30.8 per cent, 25.5 per cent and 10.5 per cent, respectively. In addition, 18 patients with undifferentiated small cell carcinoma were also evaluated. The long term survival of three of sixe patients with small peripheral lesions without metastatic lymph node involvement supports the opinion that resection of these specific lesions continues to be the treatment of choice.", "contents": "Postresection stage grouping in carcinoma of the lung. The postsurgical treatment classification and staging system for carcinoma of the lung has been evaluated in a series of 403 patients admitted to a completed prospective randomized adjuvant cancer chemotherapy trial conducted by the Veterans Administration Surgical Adjuvant Group. The proposed T, N and M classification suggested by the American Joint Committee for Cancer Staging and End Results Reporting is supported. However, the stage groupings as suggested by the Committee fails to separate adequately the various prognostic groups. This appears to be better accomplished by the stage grouping modification suggested by the Radiation Therapy Oncology Group. In the latter schema, the five year survival rate of patients with postsurgical treatment Stage I disease is 40.9 per cent; Stage II, 26.2 per cent, and Stage III, 10.5 per cent. In the Joint Committee classification, these survival rates are 30.8 per cent, 25.5 per cent and 10.5 per cent, respectively. In addition, 18 patients with undifferentiated small cell carcinoma were also evaluated. The long term survival of three of sixe patients with small peripheral lesions without metastatic lymph node involvement supports the opinion that resection of these specific lesions continues to be the treatment of choice."}
{"id": "PMID:198918", "title": "The transfer of estrone glucuronide to bile in an isolated perfused rat liver system.", "content": "An isolated rat liver perfusion system has been utilized in a study of the biliary excretion of estrone glucuronide. The estrogen was initially shown to be excreted without prior metabolism. Disappearance from the medium was rapid and biliary concentrations exceeded that in the medium by more than a thousand-fold. Disappearance rates were decreased when medium estrone glucuronide concentrations exceeded 0.29 mM. Inhibition by other steroidal conjugates, testosterone glucuronide, 2-methoxyestrone (3-hydroxy-2-methoxy-estra-1,3,5(10)-trien-17-one glucuronide and 2-hydroxyestrone (2,3-dihydroxyestra-1,3,5(10)-trien-17-one) glutathione, was also demonstrated. Phenolphthalein glucuronide, at 10 times the molar concentration of estrone glucuronide, did not affect the medium clearance of the latter compound. These findings indicate the possibility of utilizing this system for further studies of possible interactions by other organic compounds for excretion via the biliary route.", "contents": "The transfer of estrone glucuronide to bile in an isolated perfused rat liver system. An isolated rat liver perfusion system has been utilized in a study of the biliary excretion of estrone glucuronide. The estrogen was initially shown to be excreted without prior metabolism. Disappearance from the medium was rapid and biliary concentrations exceeded that in the medium by more than a thousand-fold. Disappearance rates were decreased when medium estrone glucuronide concentrations exceeded 0.29 mM. Inhibition by other steroidal conjugates, testosterone glucuronide, 2-methoxyestrone (3-hydroxy-2-methoxy-estra-1,3,5(10)-trien-17-one glucuronide and 2-hydroxyestrone (2,3-dihydroxyestra-1,3,5(10)-trien-17-one) glutathione, was also demonstrated. Phenolphthalein glucuronide, at 10 times the molar concentration of estrone glucuronide, did not affect the medium clearance of the latter compound. These findings indicate the possibility of utilizing this system for further studies of possible interactions by other organic compounds for excretion via the biliary route."}
{"id": "PMID:198921", "title": "Primary carcinoma of the liver in Malawi: a review of 24 cases.", "content": "A consecutive series of 24 cases of primary carcinoma of the liver in Malawi has been investigated. Histologically, all were hepatocellular carcinomas (HCC). All patients were African Bantus, the average age was 42.7, and the sex ratio was men 3.5:women 1. The duration of symptoms attributable to HCC was about 5 months previous to admission to hospital and was in no case preceded by clinically manifest cirrhosis. The clinical picture was rather uniform with pain in the region of the liver, emaciation and nodular hepatomegaly as the most important features. One of the patients had repeated attacks of hypoglycaemic coma. Sera from 11 out of 13 patients contained alpha-feto-protein. Hepatitis-associated antigen and antibody in the serum were found in 7 and 6 out of 16 and 14 cases respectively. Serum B12 and serum unsaturated B12 binding capacity were moderately raised in most patients. The prognosis was poor, the average time of survival was 4.8 weeks after admission. The cause of death was most frequently hepatic coma. HCC in the African Bantu shows some different features from the same disease in the Western Hemisphere: The incidence is much higher; the patients are younger. The neoplasm commonly develops in a clinically latent cirrhosis. The latter is not caused by alcohol, but is presumably a sequel of hepatitis. It is possible that aflatoxin is the carcinogenic factor, acting more readily in a cirrhotic than in a normal liver.", "contents": "Primary carcinoma of the liver in Malawi: a review of 24 cases. A consecutive series of 24 cases of primary carcinoma of the liver in Malawi has been investigated. Histologically, all were hepatocellular carcinomas (HCC). All patients were African Bantus, the average age was 42.7, and the sex ratio was men 3.5:women 1. The duration of symptoms attributable to HCC was about 5 months previous to admission to hospital and was in no case preceded by clinically manifest cirrhosis. The clinical picture was rather uniform with pain in the region of the liver, emaciation and nodular hepatomegaly as the most important features. One of the patients had repeated attacks of hypoglycaemic coma. Sera from 11 out of 13 patients contained alpha-feto-protein. Hepatitis-associated antigen and antibody in the serum were found in 7 and 6 out of 16 and 14 cases respectively. Serum B12 and serum unsaturated B12 binding capacity were moderately raised in most patients. The prognosis was poor, the average time of survival was 4.8 weeks after admission. The cause of death was most frequently hepatic coma. HCC in the African Bantu shows some different features from the same disease in the Western Hemisphere: The incidence is much higher; the patients are younger. The neoplasm commonly develops in a clinically latent cirrhosis. The latter is not caused by alcohol, but is presumably a sequel of hepatitis. It is possible that aflatoxin is the carcinogenic factor, acting more readily in a cirrhotic than in a normal liver."}
{"id": "PMID:198923", "title": "Ultrastructural localization of diaminobenzidine reactivity in leishmania donovani promastigotes.", "content": "The ultrastructural localization of the activities of two enzyme systems in the culture forms of Leishmania donovani was shown by means of the diaminobenzidine techniques. The consistent deposition of electron dense reaction product of DAB oxidation without H2O2 in the kinetoplast and mitochondrial cristae and membranes was taken as evidence of the presence of cytochrome oxidase activity and cytochrome c. In the presence of H2O2, a more intense DAB oxidation was attributed to the activity of a peroxidase, possibly cytochrome c peroxidase. Mitochondrial and kinetoplast reactions to DAB were completely inhibited by KCN, methanol-nitroprusside, and by heating to 50 degrees C for 10 min. On the other hand, no inhibitory effect was observed with 100 mM 3-amino-1,2,4-triazole. Under all conditions of incubation tested, the microbodies were completely unreactive to DAB staining, which was utilized as the basis for their identification. These organelles are rounded, moderately electron-opaque bodies with a finely granular matrix and fine tubules or cores and are limited by a single membrane. Under normal staining method, the microbodies were indistinguishable from the rounded sections of mitochondria.", "contents": "Ultrastructural localization of diaminobenzidine reactivity in leishmania donovani promastigotes. The ultrastructural localization of the activities of two enzyme systems in the culture forms of Leishmania donovani was shown by means of the diaminobenzidine techniques. The consistent deposition of electron dense reaction product of DAB oxidation without H2O2 in the kinetoplast and mitochondrial cristae and membranes was taken as evidence of the presence of cytochrome oxidase activity and cytochrome c. In the presence of H2O2, a more intense DAB oxidation was attributed to the activity of a peroxidase, possibly cytochrome c peroxidase. Mitochondrial and kinetoplast reactions to DAB were completely inhibited by KCN, methanol-nitroprusside, and by heating to 50 degrees C for 10 min. On the other hand, no inhibitory effect was observed with 100 mM 3-amino-1,2,4-triazole. Under all conditions of incubation tested, the microbodies were completely unreactive to DAB staining, which was utilized as the basis for their identification. These organelles are rounded, moderately electron-opaque bodies with a finely granular matrix and fine tubules or cores and are limited by a single membrane. Under normal staining method, the microbodies were indistinguishable from the rounded sections of mitochondria."}
{"id": "PMID:198927", "title": "Interaction of ultrasound with neoplastic tissue. III. Electron microscopic demonstration of ulstrasonic destruction of Wilms tumor and its cellular membranes.", "content": "Exposure of 300 adult, male Wistar-Furth rats bearing subcutaneous implants of Wilms tumor to a vertically oriented planar ultrasound beam consistently resulted in a marked decrease in the growth rates of the tumors with an increase in the survival times of the treated animals. Grossly, the local effects consisted of a flattening of the tumors with clean excavation of their bases. Histologically, a line of demarcation was demonstrated between the sonicated (or destroyed) and non-sonicated portions of the same rat Wilms tumors. The sonicated portions exhibited a complete loss of the normal spatial relationship between the tumor epithelium and its surrounding mesenchyme. Ghost residuals of portions of individual cytoplasmic cell borders and nuclei with condensed chromatin patterns still could be discerned. Electron microscopy demonstrated a marked destruction of the nuclear and cytoplasmic cellular membranes with a migration of destroyed condensed chromatin material into the surrounding cytoplasm.", "contents": "Interaction of ultrasound with neoplastic tissue. III. Electron microscopic demonstration of ulstrasonic destruction of Wilms tumor and its cellular membranes. Exposure of 300 adult, male Wistar-Furth rats bearing subcutaneous implants of Wilms tumor to a vertically oriented planar ultrasound beam consistently resulted in a marked decrease in the growth rates of the tumors with an increase in the survival times of the treated animals. Grossly, the local effects consisted of a flattening of the tumors with clean excavation of their bases. Histologically, a line of demarcation was demonstrated between the sonicated (or destroyed) and non-sonicated portions of the same rat Wilms tumors. The sonicated portions exhibited a complete loss of the normal spatial relationship between the tumor epithelium and its surrounding mesenchyme. Ghost residuals of portions of individual cytoplasmic cell borders and nuclei with condensed chromatin patterns still could be discerned. Electron microscopy demonstrated a marked destruction of the nuclear and cytoplasmic cellular membranes with a migration of destroyed condensed chromatin material into the surrounding cytoplasm."}
{"id": "PMID:198928", "title": "Investigations of urinary stone formation following persorption.", "content": "Persorption is the excretion in urine of particles that have been absorbed (persorbed) from the gastrointestinal tract. In experiments with rats the effect of Herbst was combined with the production of renal calcium oxalate sediments by the oral administration of ethylene glycol and acidification with ammonium chloride. We used this method to investigate whether persorbed corpuscula may represent nuclei of crystallization in the formation of renal calculi. Lead sulfide, zirconium silicate and 45Ca-labeled calcium oxalate crystals were used as persorbable model bodies. It became apparent that orally supplied lead sulfide and zirconium silicate crystals could be found in the urine and the kidneys but they did not function as crystallization centers in the calcium oxalate sediments. However, radioactive labeled calcium could be demonstrated histoautoradiographically within the renal concrements. Our experiments showed that persorbed calcium oxalate crystals can work as nuclei for stone formation.", "contents": "Investigations of urinary stone formation following persorption. Persorption is the excretion in urine of particles that have been absorbed (persorbed) from the gastrointestinal tract. In experiments with rats the effect of Herbst was combined with the production of renal calcium oxalate sediments by the oral administration of ethylene glycol and acidification with ammonium chloride. We used this method to investigate whether persorbed corpuscula may represent nuclei of crystallization in the formation of renal calculi. Lead sulfide, zirconium silicate and 45Ca-labeled calcium oxalate crystals were used as persorbable model bodies. It became apparent that orally supplied lead sulfide and zirconium silicate crystals could be found in the urine and the kidneys but they did not function as crystallization centers in the calcium oxalate sediments. However, radioactive labeled calcium could be demonstrated histoautoradiographically within the renal concrements. Our experiments showed that persorbed calcium oxalate crystals can work as nuclei for stone formation."}
{"id": "PMID:198931", "title": "Simplified assessment of pituitary-adrenal axis in a stable group of chronic hemodialysis patients.", "content": "1) A stable group of hemodialysis patients in our study do not have a normal response to the cosyntropin test; 2) although one would expect chronic renal failure patients to accommodate to hemodialysis, our study demonstrates that hemodialysis may still serve as a useful stress test; 3) the reduced response to the metyrapone suppression test in our stable group of hemodialysis patients suggests impairment of the feedback mechanism of the pituitary-adrenal axis.", "contents": "Simplified assessment of pituitary-adrenal axis in a stable group of chronic hemodialysis patients. 1) A stable group of hemodialysis patients in our study do not have a normal response to the cosyntropin test; 2) although one would expect chronic renal failure patients to accommodate to hemodialysis, our study demonstrates that hemodialysis may still serve as a useful stress test; 3) the reduced response to the metyrapone suppression test in our stable group of hemodialysis patients suggests impairment of the feedback mechanism of the pituitary-adrenal axis."}
{"id": "PMID:198946", "title": "[Banded filamentous associates in the intra- and extracellular space in connection with collagen degradation (author's transl)].", "content": "Banded fibrous associates are described in the extracellular space of connective tissue from human endometrium, Ehlers-Danlos syndrome and of tendon rupture. In the cases of morbus Dupuytren these associates are also found as intracellular inclusions. The banded structures are interpreted as states of an enzymatically induced degradation of collagen in correlation with Type-III collagen.", "contents": "[Banded filamentous associates in the intra- and extracellular space in connection with collagen degradation (author's transl)]. Banded fibrous associates are described in the extracellular space of connective tissue from human endometrium, Ehlers-Danlos syndrome and of tendon rupture. In the cases of morbus Dupuytren these associates are also found as intracellular inclusions. The banded structures are interpreted as states of an enzymatically induced degradation of collagen in correlation with Type-III collagen."}
{"id": "PMID:198947", "title": "Storage of proteins in the rough endoplasmic reticulum of human hepatocytes in a patient with normal blood proteins, on oral contraceptives.", "content": "Aspects of protein storage in the rough endoplasmic reticulum of hepatocytes, comparable with those reported in alpha1-antitrypsine (AAT) deficiency, have been observed in the course of jaundice in a woman presenting no evident abnormality in AAT or other blood proteins. In light microscopy, most hepatocytes contained characteristic globular inclusions but they were PAS negative and did not react with anti-AAT antibodies. This storage of protein ceased at the time the jaundice disappeared. Prolonged treatment with high doses of contraceptive steroids may have been involved in this peculiar reaction of the hepatocytes.", "contents": "Storage of proteins in the rough endoplasmic reticulum of human hepatocytes in a patient with normal blood proteins, on oral contraceptives. Aspects of protein storage in the rough endoplasmic reticulum of hepatocytes, comparable with those reported in alpha1-antitrypsine (AAT) deficiency, have been observed in the course of jaundice in a woman presenting no evident abnormality in AAT or other blood proteins. In light microscopy, most hepatocytes contained characteristic globular inclusions but they were PAS negative and did not react with anti-AAT antibodies. This storage of protein ceased at the time the jaundice disappeared. Prolonged treatment with high doses of contraceptive steroids may have been involved in this peculiar reaction of the hepatocytes."}
{"id": "PMID:198950", "title": "[Cytological diagnosis of salivary gland tumors].", "content": "The rationale of using clinical cytodiagnostics for preoperative recognition of salivary gland neoplasms is shown. As a result of using diagnostic puncturing in 44 examined patients the character of the pathological process was precisely determined in 88.6%, and the tumor was typed histologically in 66.7%.", "contents": "[Cytological diagnosis of salivary gland tumors]. The rationale of using clinical cytodiagnostics for preoperative recognition of salivary gland neoplasms is shown. As a result of using diagnostic puncturing in 44 examined patients the character of the pathological process was precisely determined in 88.6%, and the tumor was typed histologically in 66.7%."}
{"id": "PMID:198951", "title": "[RNA biosynthesis in the ascitic cells of Ehrlich's carcinoma and Zajdela's hepatoma under conditions of blocked oxidative phosphorylation].", "content": "In experiments in vitro on ascites tumor cells of Ehrlich carcinoma and Zajdela hepatoma the author studied the effect of 2,4-dinitrophenol (an agent dissociating respiration from phosphorylation) on respiration, glycolysis, resynthesis of ATP and synthesis of basic fractions of cytoplasmic RNA by the incorporation of labeled 3N-uridine precursor. It was shown that under optimum conditions of tumor cell incubation (phosphate-rich Igle medium) in the presence of 6.10(-4) M DNP a sharp activation of anaerobic glycosis is observed as well as increased O2 absorption and high level of ATP. Blocked phosphorylation associated with respiration renders no appreciable effect on the biosynthesis of basic fractions (4 S, 18 S, 28 S) of cytoplasmic RNA.", "contents": "[RNA biosynthesis in the ascitic cells of Ehrlich's carcinoma and Zajdela's hepatoma under conditions of blocked oxidative phosphorylation]. In experiments in vitro on ascites tumor cells of Ehrlich carcinoma and Zajdela hepatoma the author studied the effect of 2,4-dinitrophenol (an agent dissociating respiration from phosphorylation) on respiration, glycolysis, resynthesis of ATP and synthesis of basic fractions of cytoplasmic RNA by the incorporation of labeled 3N-uridine precursor. It was shown that under optimum conditions of tumor cell incubation (phosphate-rich Igle medium) in the presence of 6.10(-4) M DNP a sharp activation of anaerobic glycosis is observed as well as increased O2 absorption and high level of ATP. Blocked phosphorylation associated with respiration renders no appreciable effect on the biosynthesis of basic fractions (4 S, 18 S, 28 S) of cytoplasmic RNA."}
{"id": "PMID:198953", "title": "[Serum lipids in uterine cancer].", "content": "In 40 patients with uterine cancer changes were studied in total lipids, beta-lipoproteids and cholesterol in serum prior to, during and 4 years following the treatment. All patients were characterized by a low level of total lipids and increased cholesterol values, the former were normalized under the influence of the therapy in disappearance of the symptoms. The level of beta-lipoproteids decreased prior to the treatment was reliably increased during it only in patients with cervical cancer subjected to the combination treatment (surgery & irradiation).", "contents": "[Serum lipids in uterine cancer]. In 40 patients with uterine cancer changes were studied in total lipids, beta-lipoproteids and cholesterol in serum prior to, during and 4 years following the treatment. All patients were characterized by a low level of total lipids and increased cholesterol values, the former were normalized under the influence of the therapy in disappearance of the symptoms. The level of beta-lipoproteids decreased prior to the treatment was reliably increased during it only in patients with cervical cancer subjected to the combination treatment (surgery & irradiation)."}
{"id": "PMID:198954", "title": "[Transforming action of the total RNA preparations isolated from Rous virus-induced sarcomas].", "content": "The authors compared the effect of RNA substances isolated from chick sarcomas producing Rous virus and hamster sarcomas not producing the virus. In both species of animals the tumors were induced by the same Rous virus strain (Carr-Zilber). The treatment of embryonal cells cultures both of the chick and hamster with RNA preparations resulted in the morphological transformation. The action of RNA-s would reduce considerably or eliminated totally the effect, while DNA-s failed to influence the activity of the preparations under study. Embryonal cells culture in hamsters proved to be more sensitive to RNA action than chick cells.", "contents": "[Transforming action of the total RNA preparations isolated from Rous virus-induced sarcomas]. The authors compared the effect of RNA substances isolated from chick sarcomas producing Rous virus and hamster sarcomas not producing the virus. In both species of animals the tumors were induced by the same Rous virus strain (Carr-Zilber). The treatment of embryonal cells cultures both of the chick and hamster with RNA preparations resulted in the morphological transformation. The action of RNA-s would reduce considerably or eliminated totally the effect, while DNA-s failed to influence the activity of the preparations under study. Embryonal cells culture in hamsters proved to be more sensitive to RNA action than chick cells."}
{"id": "PMID:198956", "title": "[Kinetic study of the effectiveness of chemotherapy of experimental metastases (using a computer)].", "content": "Under study was the influence of active antitumor substances on experimental metastasizing tumors. The method for assessment of their efficacy, using an electronic computer, is suggested. Significant differences in the action of the substances on primary tumors and their metastases are shown.", "contents": "[Kinetic study of the effectiveness of chemotherapy of experimental metastases (using a computer)]. Under study was the influence of active antitumor substances on experimental metastasizing tumors. The method for assessment of their efficacy, using an electronic computer, is suggested. Significant differences in the action of the substances on primary tumors and their metastases are shown."}
{"id": "PMID:198957", "title": "[Study of viremia in chronic human herpetic infection].", "content": "Attempts at virus isolation were made on the blood specimens from patients with relapsing herpesvirus infection. Examinations of over 100 blood specimens from patients with various localizations of herpetic lesions yielded II strains of herpesvirus. In all the cases the virus was isolated from a mixture of leukocytes with erythrocytes of the blood of patients. The method of cocultivation of blood leukocytes with cell cultures was most sensitive and yielded 7 herpesvirus isolates. The herpesvirus isolates vary in their biological and antigenic properties.", "contents": "[Study of viremia in chronic human herpetic infection]. Attempts at virus isolation were made on the blood specimens from patients with relapsing herpesvirus infection. Examinations of over 100 blood specimens from patients with various localizations of herpetic lesions yielded II strains of herpesvirus. In all the cases the virus was isolated from a mixture of leukocytes with erythrocytes of the blood of patients. The method of cocultivation of blood leukocytes with cell cultures was most sensitive and yielded 7 herpesvirus isolates. The herpesvirus isolates vary in their biological and antigenic properties."}
{"id": "PMID:198958", "title": "[Transfection by integrated proviruses].", "content": "Three lines of continuous mouse L cells were compared: one of them contained only its endogenic oncornavirus, another was contaminated with SV5 virus, and a third was obtained from the second line chronically infected with vesicular stomatitis virus. Experiments with transfection showed that it was possible to recover SV5 virus from the two former cultures and vesicular stomatitis virus from the latter.", "contents": "[Transfection by integrated proviruses]. Three lines of continuous mouse L cells were compared: one of them contained only its endogenic oncornavirus, another was contaminated with SV5 virus, and a third was obtained from the second line chronically infected with vesicular stomatitis virus. Experiments with transfection showed that it was possible to recover SV5 virus from the two former cultures and vesicular stomatitis virus from the latter."}
{"id": "PMID:198960", "title": "[Study of the antigenic properties of herpesvirus strains isolated from herpetic lesions at different sites].", "content": "The antigenic properties of 15 strains of hepesvirus isolated from herpetic lesions of different localization were studied. The serotype of each strain was established by the neutralization tests with hyperimmune sera to the reference type 1 and 2 strains: the cross-neutralization tests revealed antigenic relationships between the strains of 1 and 2 serotypes. Most strains isolated from lesions of the genitalia belonged to type 2, although one strain isolated in herpes genitalis belonged to type 1, and 2 strains isolated from facial lesions also belonged to type 2. These results confirm the necessity of using inactivated polyvaccine prepared from herpesvirus strains of antigenic types 1 and 2 for relapse control therapy instead of using monovalent type 1 and type 2 vaccines as reported by foreign authors.", "contents": "[Study of the antigenic properties of herpesvirus strains isolated from herpetic lesions at different sites]. The antigenic properties of 15 strains of hepesvirus isolated from herpetic lesions of different localization were studied. The serotype of each strain was established by the neutralization tests with hyperimmune sera to the reference type 1 and 2 strains: the cross-neutralization tests revealed antigenic relationships between the strains of 1 and 2 serotypes. Most strains isolated from lesions of the genitalia belonged to type 2, although one strain isolated in herpes genitalis belonged to type 1, and 2 strains isolated from facial lesions also belonged to type 2. These results confirm the necessity of using inactivated polyvaccine prepared from herpesvirus strains of antigenic types 1 and 2 for relapse control therapy instead of using monovalent type 1 and type 2 vaccines as reported by foreign authors."}
{"id": "PMID:198962", "title": "[Study of the morphological aspects of Okhotski\u012d virus replication in a chick fibroblast culture].", "content": "Electron microscopic studies of chick embryo fibroblast cells 24 hours after infection with Okhotsky virus revealed changes typical orbivirus infection in the cytoplasm and the nuclei of the cells. The nuclei of the infected cells contained fine-granular matrices with forming virus particles and tubular structures. The cell cytoplasm also contained tubular structures, crystal arrays, fine-granular matrices and virus particles 50-60 nm in diameter.", "contents": "[Study of the morphological aspects of Okhotski\u012d virus replication in a chick fibroblast culture]. Electron microscopic studies of chick embryo fibroblast cells 24 hours after infection with Okhotsky virus revealed changes typical orbivirus infection in the cytoplasm and the nuclei of the cells. The nuclei of the infected cells contained fine-granular matrices with forming virus particles and tubular structures. The cell cytoplasm also contained tubular structures, crystal arrays, fine-granular matrices and virus particles 50-60 nm in diameter."}
{"id": "PMID:198963", "title": "[Herpetic infection of the oral cavity in guinea pigs].", "content": "A convenient experimental model for serial studies of herpes simplex of the buccal mucosa has been developed in guinea pigs by application of fresh isolates of herpes simplex virus type 1 from a patient with primary herpetic gingivo-stomatitis on prescarified buccal mucosa. The herpetic nature of the eruptions in the oral cavity was confirmed by virus isolations and serologically. The possibility of exogenous reinfection of the buccal mucosa in convalescent animals against the background of humoral virus-neutralizing antibody has been demonstrated. No virus was isolated from the blood, brain, regional lymph nodes, oesophagus, trachea, lungs or liver of the animals with primary herpes simplex of the buccal mucosa. The model is recommended for experimental investigations of herpetic infections of the buccal mucosa.", "contents": "[Herpetic infection of the oral cavity in guinea pigs]. A convenient experimental model for serial studies of herpes simplex of the buccal mucosa has been developed in guinea pigs by application of fresh isolates of herpes simplex virus type 1 from a patient with primary herpetic gingivo-stomatitis on prescarified buccal mucosa. The herpetic nature of the eruptions in the oral cavity was confirmed by virus isolations and serologically. The possibility of exogenous reinfection of the buccal mucosa in convalescent animals against the background of humoral virus-neutralizing antibody has been demonstrated. No virus was isolated from the blood, brain, regional lymph nodes, oesophagus, trachea, lungs or liver of the animals with primary herpes simplex of the buccal mucosa. The model is recommended for experimental investigations of herpetic infections of the buccal mucosa."}
{"id": "PMID:198964", "title": "[Immunofluorescent method of studying autopsy material in acute pneumonia].", "content": "The immunofluorescent procedure in examinations of the autopsy material from 304 fatal cases hospitalized for acute pneumonia permitted to diagnose influenza A2 in 29.0%, influenza B in 18.1%, parainfluenza in 3.5%, adenovirus infection in 9.2% and respiratory syncytial virus infection in 3.5% of the cases. In the period of a high incidence of acute respiratory infection, influenza A2 was detected by this method in 40.9% and influenza B in 50% of the cases. Simultaneous examinations of the material in the influenza epidemic period by virological and immunofluorescent methods (63 cases) in 13 cases positive results were obtained with both methods, in 6 cases where influenza viruses were detected the immunofluorescent test was negative, and in 28 cases the positive diagnosis by the immunofluorescent test could not be confirmed virologically. Among the cases examined, 33 were found by the immunofluorescence test to have a mixed respiratory infection, including influenza A2 with other forms of respiratory infection in 18, and influenza B with other respiratory infections in 19 cases. Serological examinations by the complement fixation and hemagglutination inhibition tests on the blood from fatal cases irrespective of the time of examination, as a rule, revealed antibody in low titres which did not confirm the diagnosis.", "contents": "[Immunofluorescent method of studying autopsy material in acute pneumonia]. The immunofluorescent procedure in examinations of the autopsy material from 304 fatal cases hospitalized for acute pneumonia permitted to diagnose influenza A2 in 29.0%, influenza B in 18.1%, parainfluenza in 3.5%, adenovirus infection in 9.2% and respiratory syncytial virus infection in 3.5% of the cases. In the period of a high incidence of acute respiratory infection, influenza A2 was detected by this method in 40.9% and influenza B in 50% of the cases. Simultaneous examinations of the material in the influenza epidemic period by virological and immunofluorescent methods (63 cases) in 13 cases positive results were obtained with both methods, in 6 cases where influenza viruses were detected the immunofluorescent test was negative, and in 28 cases the positive diagnosis by the immunofluorescent test could not be confirmed virologically. Among the cases examined, 33 were found by the immunofluorescence test to have a mixed respiratory infection, including influenza A2 with other forms of respiratory infection in 18, and influenza B with other respiratory infections in 19 cases. Serological examinations by the complement fixation and hemagglutination inhibition tests on the blood from fatal cases irrespective of the time of examination, as a rule, revealed antibody in low titres which did not confirm the diagnosis."}
{"id": "PMID:198965", "title": "[Quantitative indices and physico-chemical properties of non-specific inhibitors of influenza A virus hemagglutination in the sera of different species of animals and birds].", "content": "The results of studies of the quantitative values of nonspecific antihemagglutinins of influenza viruses in the sera of birds, laboratory, wild and domestic animals (altogether 27 species) are presented. The antiviral inhibitors characterized by a number of physicochemical properties (sensitivity to heating, KIO4, trypsin, rivanol, 2-mercaptoethanol) were divided into 3 groups, sera of sheep, goats and cattle making up a separate group with regard to their sensitivity to heating and treatment with KIO4. Studies using molecular screen chromatography demonstrated the nonspecific inhibitors present in bovine sera to be heterogenous both in type (thermolabile and thermostable) and in the molecular composition. Alongside with thermolabile inhibitors of macroglobulin nature, thermostabe 19S and 4S inhibitors were identified.", "contents": "[Quantitative indices and physico-chemical properties of non-specific inhibitors of influenza A virus hemagglutination in the sera of different species of animals and birds]. The results of studies of the quantitative values of nonspecific antihemagglutinins of influenza viruses in the sera of birds, laboratory, wild and domestic animals (altogether 27 species) are presented. The antiviral inhibitors characterized by a number of physicochemical properties (sensitivity to heating, KIO4, trypsin, rivanol, 2-mercaptoethanol) were divided into 3 groups, sera of sheep, goats and cattle making up a separate group with regard to their sensitivity to heating and treatment with KIO4. Studies using molecular screen chromatography demonstrated the nonspecific inhibitors present in bovine sera to be heterogenous both in type (thermolabile and thermostable) and in the molecular composition. Alongside with thermolabile inhibitors of macroglobulin nature, thermostabe 19S and 4S inhibitors were identified."}
{"id": "PMID:198967", "title": "[Interaction of Sindbis virus with a culture of cells producing oncornavirus].", "content": "Electron microscopy and biophysical methods were used for examinations of primarily trypsinized chick fibroblast cell culture spontaneously producing C-type oncornavirus at 1, 6, and 24 hours after inoculation with Sindbis virus. During the first 6 hours rapid maturation and release of oncornavirus from cells were observed. At later intervals oncornavirus production was inhibited. It is assumed that in the system under study, biosynthesis of oncornavirus and Sindbis virus occur separately.", "contents": "[Interaction of Sindbis virus with a culture of cells producing oncornavirus]. Electron microscopy and biophysical methods were used for examinations of primarily trypsinized chick fibroblast cell culture spontaneously producing C-type oncornavirus at 1, 6, and 24 hours after inoculation with Sindbis virus. During the first 6 hours rapid maturation and release of oncornavirus from cells were observed. At later intervals oncornavirus production was inhibited. It is assumed that in the system under study, biosynthesis of oncornavirus and Sindbis virus occur separately."}
{"id": "PMID:198966", "title": "[Sensitivity of Japanese quail, embryos and embryonal tissue culture to infection with several avian viruses].", "content": "The sensitivity of the biological system Japanese quail-embryo-quail fibroblast cultures to some common fowl viruses (Newcastle disease virus, infectious laryngotracheitis and infectious bronchitis viruses) was studied. Japanese quails, their embryos and embryo cell cultures were found to be sensitive to Newcastle disease virus infection. The virus reproduction was accompanied by death of embryos and destruction of cell culture. Japanese quails are sensitive to infectious laryngotracheitis virus given as aerosol. Reproduction of this virus in embryos was accompanied by formation of plaques on the chorioallantoic membrane and in the cell cultures by incomplete cytopathic effect. Japanese quails were found to be sensitive to infectious bronchitis virus, while their embryos and embryo cell cultures had low susceptibility to this virus.", "contents": "[Sensitivity of Japanese quail, embryos and embryonal tissue culture to infection with several avian viruses]. The sensitivity of the biological system Japanese quail-embryo-quail fibroblast cultures to some common fowl viruses (Newcastle disease virus, infectious laryngotracheitis and infectious bronchitis viruses) was studied. Japanese quails, their embryos and embryo cell cultures were found to be sensitive to Newcastle disease virus infection. The virus reproduction was accompanied by death of embryos and destruction of cell culture. Japanese quails are sensitive to infectious laryngotracheitis virus given as aerosol. Reproduction of this virus in embryos was accompanied by formation of plaques on the chorioallantoic membrane and in the cell cultures by incomplete cytopathic effect. Japanese quails were found to be sensitive to infectious bronchitis virus, while their embryos and embryo cell cultures had low susceptibility to this virus."}
{"id": "PMID:198968", "title": "[Mechanism of postvaccinal immunity in Marek's disease].", "content": "The apathogenic variant No. 38 of Marek's disease virus, Kekava strain (MDV-Kekava), at the level of the 16th and 45th passages in vitro made chickens resistant to Marek's disease when inoculated 14 days before the infection of the chickens with the pathogenic variant No. 55 of MDV-Kekava. A simultaneous administration of both variants did not protect the animals against the disease. The occurrence in variants of MDV-Kekava of genetic markets manifest upon virus passages in chick embryo fibroblast (CEF) cultures provided an opportunity to study the interactions between them in chickens, using the CEF culture for virus isolation. The results of virus isolation from the blood cells of vaccinated chickens showed interference to occur in chickens between the virus variants as the rate of isolation of the pathogenic variant was 3 times as low as that of apathogenic MDV-Kekava, and both virus variants persisted in different cells. When chickens were inoculated simultaneously with both virus variants, the recovery rate of both pathogenic and apathogenic variants from the blood cells was similar. In such cases, persistence of two virus variants in one cell is also possible. The experimental results suggest that in the mechanism of resistance of vaccinated chickens to Marek's disease a significant role may be played by interference between the viruses in which the \"occupation\" of target cells by vaccine virus protects them from pathogenic MDV.", "contents": "[Mechanism of postvaccinal immunity in Marek's disease]. The apathogenic variant No. 38 of Marek's disease virus, Kekava strain (MDV-Kekava), at the level of the 16th and 45th passages in vitro made chickens resistant to Marek's disease when inoculated 14 days before the infection of the chickens with the pathogenic variant No. 55 of MDV-Kekava. A simultaneous administration of both variants did not protect the animals against the disease. The occurrence in variants of MDV-Kekava of genetic markets manifest upon virus passages in chick embryo fibroblast (CEF) cultures provided an opportunity to study the interactions between them in chickens, using the CEF culture for virus isolation. The results of virus isolation from the blood cells of vaccinated chickens showed interference to occur in chickens between the virus variants as the rate of isolation of the pathogenic variant was 3 times as low as that of apathogenic MDV-Kekava, and both virus variants persisted in different cells. When chickens were inoculated simultaneously with both virus variants, the recovery rate of both pathogenic and apathogenic variants from the blood cells was similar. In such cases, persistence of two virus variants in one cell is also possible. The experimental results suggest that in the mechanism of resistance of vaccinated chickens to Marek's disease a significant role may be played by interference between the viruses in which the \"occupation\" of target cells by vaccine virus protects them from pathogenic MDV."}
{"id": "PMID:198969", "title": "[Differences in the antiviral and antioncogenic action of interferons produced in murine peritoneal cells and in Krebs-2 ascitic carcinoma cells].", "content": "Comparisons of native preparation of mouse interferons, \"macrophage\" and \"Krebs\" revealed some differences, Thus, the minimal time necessary for the development of resistance to vesicular stomatitis virus (VSV) in L cells treated with \"macrophage\" and \"Krebs\" interferon was 5 and 2 hours, respectively. The activity of the lysosomal enzyme of acid phosphatase was considerably higher in the cells treated with \"Krebs\" interferon and infected with VSV than with \"macrophage\" interferon. Differences in the antiviral and antioncogenic properties of fractions No. 1 and No. 5 of these interferons obtained in fractionation of native interferon preparations by the cryomethod were demonstrated. In particular, fraction No. 5 of \"Krebs\" interferon, in contrast to that of \"macrophage\" interferon, had no antioncogenic properties but did have antiviral properties. It is suggested that these differences are due to the presence in native preparations of different substances capable of exerting an effect on interferon.", "contents": "[Differences in the antiviral and antioncogenic action of interferons produced in murine peritoneal cells and in Krebs-2 ascitic carcinoma cells]. Comparisons of native preparation of mouse interferons, \"macrophage\" and \"Krebs\" revealed some differences, Thus, the minimal time necessary for the development of resistance to vesicular stomatitis virus (VSV) in L cells treated with \"macrophage\" and \"Krebs\" interferon was 5 and 2 hours, respectively. The activity of the lysosomal enzyme of acid phosphatase was considerably higher in the cells treated with \"Krebs\" interferon and infected with VSV than with \"macrophage\" interferon. Differences in the antiviral and antioncogenic properties of fractions No. 1 and No. 5 of these interferons obtained in fractionation of native interferon preparations by the cryomethod were demonstrated. In particular, fraction No. 5 of \"Krebs\" interferon, in contrast to that of \"macrophage\" interferon, had no antioncogenic properties but did have antiviral properties. It is suggested that these differences are due to the presence in native preparations of different substances capable of exerting an effect on interferon."}
{"id": "PMID:198973", "title": "Survival in lung cancer.", "content": "Analysis was carried out according to stage and tissue type of 392 consecutive cases of lung cancer diagnosed at David Grant Medical Center between 1960 and 1974. Biphasic survival curves were described with a variable primary phase and a constant (1.1 percent per month) secondary phase. Survival was found to correlate both to histology and stage. The best survival was found in stage I bronchoalveolar carcinoma. Even in the more favorable categories a leveling off of survival was not found. This study strongly suggests that surgical treatment of lung cancer, while beneficial, cannot expect to be considered as a curative procedure in more than 10 percent of cases. Radiotherapy did not prolong survival.", "contents": "Survival in lung cancer. Analysis was carried out according to stage and tissue type of 392 consecutive cases of lung cancer diagnosed at David Grant Medical Center between 1960 and 1974. Biphasic survival curves were described with a variable primary phase and a constant (1.1 percent per month) secondary phase. Survival was found to correlate both to histology and stage. The best survival was found in stage I bronchoalveolar carcinoma. Even in the more favorable categories a leveling off of survival was not found. This study strongly suggests that surgical treatment of lung cancer, while beneficial, cannot expect to be considered as a curative procedure in more than 10 percent of cases. Radiotherapy did not prolong survival."}
{"id": "PMID:198974", "title": "The biology of the rheumatoid synovial cell.", "content": "Over the past 15 years, many of the elaborate research techniques of cell biology and biochemistry have been applied toward discovering the cause of rheumatoid arthritis. Consequently, it is valuable to review the morphological, physiological and biochemical alterations that have been observed in rheumatoid synovial cells. All of the changes observed suggest that a viral agent may form the basis for these alterations. However, studies to date have failed to isolate or identify the putative causative virus and the search continues.", "contents": "The biology of the rheumatoid synovial cell. Over the past 15 years, many of the elaborate research techniques of cell biology and biochemistry have been applied toward discovering the cause of rheumatoid arthritis. Consequently, it is valuable to review the morphological, physiological and biochemical alterations that have been observed in rheumatoid synovial cells. All of the changes observed suggest that a viral agent may form the basis for these alterations. However, studies to date have failed to isolate or identify the putative causative virus and the search continues."}
{"id": "PMID:198976", "title": "[Therapeutic and diagnostic problems in a patient with insulinoma (author's transl)].", "content": "Surgical intervention in organic hyperinsulinism is based on prior accurate biochemical assessment. The emergent problems are discussed in a case with hypoglycaemic attacks, where \"blind\" pancreatic resections had been performed in two occasions without success. Finally, after demonstration of hyperinsulinaemia and localization of the tumour by selective angiography an adenoma was removed surgically. The postoperative complications, including the development of insulin-dependent diabetes, demonstrate the inherent risks of blind distal pancreatectomy for suspected insulinoma.", "contents": "[Therapeutic and diagnostic problems in a patient with insulinoma (author's transl)]. Surgical intervention in organic hyperinsulinism is based on prior accurate biochemical assessment. The emergent problems are discussed in a case with hypoglycaemic attacks, where \"blind\" pancreatic resections had been performed in two occasions without success. Finally, after demonstration of hyperinsulinaemia and localization of the tumour by selective angiography an adenoma was removed surgically. The postoperative complications, including the development of insulin-dependent diabetes, demonstrate the inherent risks of blind distal pancreatectomy for suspected insulinoma."}
{"id": "PMID:198982", "title": "[Secondary hyperlipoproteinemias].", "content": "At first the review deals with significance of the apoproteins for the metabolism of the lipoproteins, especially VLDL. Thus, for instance the apo-C is a cofactor for the lipase of the fatty tissue which hydrolyses the chylomicron-TG. The author enters examples of the secondary hyperlipoproteinaemias: hyperlipoproteinaemias in diseases of the liver and of the kidneys, in pancreatitis and in diabetes. In cholestasis an abnormal lipoprotein called LP-X is observed, in other diseases of the liver the beta2LP corresponding to the VLDL-intermediate. Causes for increases of lipoproteins in renal diseases are probably disturbances of the protein metabolism. There are close correlations between hyperlipoproteinaemias and pancreatitis. In diabetes primary hyperlipoproteinaemias in maturity-onset-diabetes are to be differed from clearly secondary ones in juvenile-onset-diabetes as well as such ones in nephropathy. The therapy of the secondary hyperlipoproteinaemias is shortly discussed.", "contents": "[Secondary hyperlipoproteinemias]. At first the review deals with significance of the apoproteins for the metabolism of the lipoproteins, especially VLDL. Thus, for instance the apo-C is a cofactor for the lipase of the fatty tissue which hydrolyses the chylomicron-TG. The author enters examples of the secondary hyperlipoproteinaemias: hyperlipoproteinaemias in diseases of the liver and of the kidneys, in pancreatitis and in diabetes. In cholestasis an abnormal lipoprotein called LP-X is observed, in other diseases of the liver the beta2LP corresponding to the VLDL-intermediate. Causes for increases of lipoproteins in renal diseases are probably disturbances of the protein metabolism. There are close correlations between hyperlipoproteinaemias and pancreatitis. In diabetes primary hyperlipoproteinaemias in maturity-onset-diabetes are to be differed from clearly secondary ones in juvenile-onset-diabetes as well as such ones in nephropathy. The therapy of the secondary hyperlipoproteinaemias is shortly discussed."}
{"id": "PMID:198983", "title": "Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo.", "content": "We have recently reported that fetal BD IX-rat brain cells (FBC), transferred to long-term culture after a transplacental pulse of EtNU on the 18th day of gestation, undergo neoplastic transformation in vitro (\"BT-cell lines\"). Tumors developed upon s.c. reimplantation of BT-cells into baby BD IX-rats, appeared histologically as neurinoma-, glioma- or glioblastoma-like, and frequently as pleiomorphic neoplasms. In spite of a more atypic cellular morphology, these tumors grossly resembled the different types of neuroectodermal rat neoplasms induced by EtNU in vivo. Like the neoplastic cell culture lines derived from EtNU-induced, neuroectodermal BD IX-rat tumors (\"V-cell lines\"), the BT-lines contained multipolar glia-like cells, but also flat cells with fewer and shorter cytoplasmic processes, and occasionally giant cells. Both the V- and BT-lines showed different levels of aneuploidy. They contained multiple subpopulations of cells, as reflected, e.g., by plurimodal pulse-cytophotometric DNA distributions. All lines contained, to varying degrees, the nervous system-specific protein S-100, a \"marker\" not yet expressed in FBC. There was no indication of more than borderline neurotransmitter activity, suggesting that proliferating (precursor) cells of glial lineages may preferentially undergo malignant transformation after exposure to EtNU during this stage of brain development.", "contents": "Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. We have recently reported that fetal BD IX-rat brain cells (FBC), transferred to long-term culture after a transplacental pulse of EtNU on the 18th day of gestation, undergo neoplastic transformation in vitro (\"BT-cell lines\"). Tumors developed upon s.c. reimplantation of BT-cells into baby BD IX-rats, appeared histologically as neurinoma-, glioma- or glioblastoma-like, and frequently as pleiomorphic neoplasms. In spite of a more atypic cellular morphology, these tumors grossly resembled the different types of neuroectodermal rat neoplasms induced by EtNU in vivo. Like the neoplastic cell culture lines derived from EtNU-induced, neuroectodermal BD IX-rat tumors (\"V-cell lines\"), the BT-lines contained multipolar glia-like cells, but also flat cells with fewer and shorter cytoplasmic processes, and occasionally giant cells. Both the V- and BT-lines showed different levels of aneuploidy. They contained multiple subpopulations of cells, as reflected, e.g., by plurimodal pulse-cytophotometric DNA distributions. All lines contained, to varying degrees, the nervous system-specific protein S-100, a \"marker\" not yet expressed in FBC. There was no indication of more than borderline neurotransmitter activity, suggesting that proliferating (precursor) cells of glial lineages may preferentially undergo malignant transformation after exposure to EtNU during this stage of brain development."}
{"id": "PMID:198984", "title": "On the function of hormone receptors in the action of steroidal alkylating agents.", "content": "Steroidal alkylating agents are supposed to bind to steroid hormone receptors in target tissues. By this interaction the steroid portion might act as a carrier for the alkylating group. Three steroidal agents (phenesterin, estradiol mustard, dehydroepiandrosterone mustard) were tested for their capacity to combine with estrogen and androgen receptors in normal and malignant target tissues. For measuring steroid receptor complexes ager gel electrophoresis was used. All three compounds (added at a 10(3)-fold excess) revealed in vitro no competition to receptor sites (estrogen and androgen binding). After preincubation of intact tissue estrogen mustard was effective in inhibiting the binding of 3H-estradiol and dehydroepiandrosterone mustard reduced the uptake of 3H-5alpha-DHT. This may be due to liberating of estradiol and dehydroepiandrosterone, respectively, from the intact molecule. From these data it is unlikely that the cytostatic steroidal agents are more effective than other alkylating drugs.", "contents": "On the function of hormone receptors in the action of steroidal alkylating agents. Steroidal alkylating agents are supposed to bind to steroid hormone receptors in target tissues. By this interaction the steroid portion might act as a carrier for the alkylating group. Three steroidal agents (phenesterin, estradiol mustard, dehydroepiandrosterone mustard) were tested for their capacity to combine with estrogen and androgen receptors in normal and malignant target tissues. For measuring steroid receptor complexes ager gel electrophoresis was used. All three compounds (added at a 10(3)-fold excess) revealed in vitro no competition to receptor sites (estrogen and androgen binding). After preincubation of intact tissue estrogen mustard was effective in inhibiting the binding of 3H-estradiol and dehydroepiandrosterone mustard reduced the uptake of 3H-5alpha-DHT. This may be due to liberating of estradiol and dehydroepiandrosterone, respectively, from the intact molecule. From these data it is unlikely that the cytostatic steroidal agents are more effective than other alkylating drugs."}
{"id": "PMID:198985", "title": "[Transplacental induction of neurogenic tumors in rabbits (author's transl)].", "content": "The oncogenic effect of ethylnitrosourea (ENU) on rabbits during the organogenesis was studied. ENU, dissolved in sodium phosphate (pH 6.0), was injected in a 50 mg/kg dosis intravenously in pregnant dams between the 8th and 10th day of gestation. From 12 offspring 8 grew up normally and appeared unremarkably until 30--36 months of age when neurologic signs first developed. Six rabbits showed one or more tumors along the peripheral nerves. Two rabbits were bearing brain gliomas in the vicinity of the 3rd ventricle. The tumors of the peripheral nervous system (PNS) were of variable size and soft consistency; they had a cut surface of spongy and even cystic appearance. Histologically, the PNS tumors resemble Schwannomas of the Antoni B type. An ultrastructural study of these neoplasms disclosed cells featuring a basal lamina type of lining characteristics of Schwann cells. These findings demonstrate that the exposure of rabbits to ENU during organogenesis results in the induction of neurogenic tumors which become clinically manifest late in life. It seems, therefore, that the selective oncogenic effect of ENU on the nervous tissues of the exposed animals depends exclusively on the stage of organogenesis at which the drug is brought to bear upon the target organ anlage.", "contents": "[Transplacental induction of neurogenic tumors in rabbits (author's transl)]. The oncogenic effect of ethylnitrosourea (ENU) on rabbits during the organogenesis was studied. ENU, dissolved in sodium phosphate (pH 6.0), was injected in a 50 mg/kg dosis intravenously in pregnant dams between the 8th and 10th day of gestation. From 12 offspring 8 grew up normally and appeared unremarkably until 30--36 months of age when neurologic signs first developed. Six rabbits showed one or more tumors along the peripheral nerves. Two rabbits were bearing brain gliomas in the vicinity of the 3rd ventricle. The tumors of the peripheral nervous system (PNS) were of variable size and soft consistency; they had a cut surface of spongy and even cystic appearance. Histologically, the PNS tumors resemble Schwannomas of the Antoni B type. An ultrastructural study of these neoplasms disclosed cells featuring a basal lamina type of lining characteristics of Schwann cells. These findings demonstrate that the exposure of rabbits to ENU during organogenesis results in the induction of neurogenic tumors which become clinically manifest late in life. It seems, therefore, that the selective oncogenic effect of ENU on the nervous tissues of the exposed animals depends exclusively on the stage of organogenesis at which the drug is brought to bear upon the target organ anlage."}
{"id": "PMID:198986", "title": "Specifically immune mouse T-cells can destroy H-2 compatible murine target cells infected with herpes simplex virus types 1 or 2.", "content": "Lymphocytes from the spleen (SL) or peritoneal cavities (PL) of HSV-1- or HSV-2-immunized C 3 H mice expressed pronounced cytotoxicity, as measured by 51Cr release assay, against L cells experimentally infected with HSF-types 1 or 2 but not against uninfected L cells. HSV-1 or HSV-2 immune lymphocytes induced substantially more 51Cr release when L-cell targets were infected with homotypic virus compared to those infected with heterotypic virus. Inasmuch as the cytotoxicity of specifically immune C 3 H SL for HSV-infected L cells was selectively eliminated by treatment with AKR anti-theta C 3 H serum plus complement, the effector cells in present system were theta-bearing T cells. Evidence has been provided which indicates that specifically immune T cells express cytotoxicity exclusively directed against different HSV-infected target cells (mouse embryo cells or mouse peritoneal macrophages) which share H-2 antigens with the effector cells.", "contents": "Specifically immune mouse T-cells can destroy H-2 compatible murine target cells infected with herpes simplex virus types 1 or 2. Lymphocytes from the spleen (SL) or peritoneal cavities (PL) of HSV-1- or HSV-2-immunized C 3 H mice expressed pronounced cytotoxicity, as measured by 51Cr release assay, against L cells experimentally infected with HSF-types 1 or 2 but not against uninfected L cells. HSV-1 or HSV-2 immune lymphocytes induced substantially more 51Cr release when L-cell targets were infected with homotypic virus compared to those infected with heterotypic virus. Inasmuch as the cytotoxicity of specifically immune C 3 H SL for HSV-infected L cells was selectively eliminated by treatment with AKR anti-theta C 3 H serum plus complement, the effector cells in present system were theta-bearing T cells. Evidence has been provided which indicates that specifically immune T cells express cytotoxicity exclusively directed against different HSV-infected target cells (mouse embryo cells or mouse peritoneal macrophages) which share H-2 antigens with the effector cells."}
{"id": "PMID:198987", "title": "[The properties of [omega(3-acetylpyridinio)-n-alkyl]adenosine pyrophosphates, structural analogs of the coenzyme NAD (author's transl)].", "content": "[omega-(3-Acetylpyridinio)-n-alkyl]adenosine pyrophosphates are coenzyme analogs of NAD. The adenosine pyrophosphate moiety and the 3-acetylpyridine ring of the analogs are connected by n-alkyl chains of different lengths (ethyl--hexyl). The analogs form strong dissociating complexes with lactate dehydrogenase. The complex formation is predominantly achieved by interaction of the ADP moiety with its respective binding domain at the active site. The redox potentials of the analogs and NAD are of similar magnitude. The coenzyme function of the analogs depends upon the length of the hydrocarbon chain. Lactate dehydrogenase and alcohol dehydrogenases from yeast and horse liver do not catalize hydrogen transfer from their substrates to any other alkyl analog but [4-(3-acetylpyridinio)-n-butyl]adenosine pyrophosphate, aldehyde dehydrogenase from horse liver catalizes hydrogen transfer from acetaldehyde to the pentyl derivative and glyceraldehyde-3-phosphate dehydrogenase catalizes hydrogen transfer to both analogs. In no case, hydrogen transfer from or to one of the 3-acetylpyridine-n-alkyl analogs proceeded with a velocity comparable to NAD or its 3-acetylpyridine analog. The results show that the nicotinamide bound ribose in NAD is involved in the binding and the activation of the coenzyme.", "contents": "[The properties of [omega(3-acetylpyridinio)-n-alkyl]adenosine pyrophosphates, structural analogs of the coenzyme NAD (author's transl)]. [omega-(3-Acetylpyridinio)-n-alkyl]adenosine pyrophosphates are coenzyme analogs of NAD. The adenosine pyrophosphate moiety and the 3-acetylpyridine ring of the analogs are connected by n-alkyl chains of different lengths (ethyl--hexyl). The analogs form strong dissociating complexes with lactate dehydrogenase. The complex formation is predominantly achieved by interaction of the ADP moiety with its respective binding domain at the active site. The redox potentials of the analogs and NAD are of similar magnitude. The coenzyme function of the analogs depends upon the length of the hydrocarbon chain. Lactate dehydrogenase and alcohol dehydrogenases from yeast and horse liver do not catalize hydrogen transfer from their substrates to any other alkyl analog but [4-(3-acetylpyridinio)-n-butyl]adenosine pyrophosphate, aldehyde dehydrogenase from horse liver catalizes hydrogen transfer from acetaldehyde to the pentyl derivative and glyceraldehyde-3-phosphate dehydrogenase catalizes hydrogen transfer to both analogs. In no case, hydrogen transfer from or to one of the 3-acetylpyridine-n-alkyl analogs proceeded with a velocity comparable to NAD or its 3-acetylpyridine analog. The results show that the nicotinamide bound ribose in NAD is involved in the binding and the activation of the coenzyme."}
{"id": "PMID:198988", "title": "Stimulation of tyrosinase activity and melanin formation of cultured melanoma cells by serum deprivation alone or in combination with dibutyryl cyclic AMP and theophylline.", "content": "Serum removal from the media of serial monolayer cultures of the Harding-Passey melanoma during an incubation period of 3 days resulted in an exponentially declining DNA synthesis rate (measured by the incorporation of [14C]thymidine) and in an inhibition of cell proliferation. Protein synthesis, as measured by the incorporation of radioactive leucine, was less affected than DNA synthesis. Incubation in serum-free culture medium resulted in significant rises of tyrosinase activity and cellular melanin content. Addition of dibutyryl adenosine 3':5' monophosphate (Bu2cAMP, 5X10(-4) M) and theophylline (5X10(-4) M) to serum-free cultures caused a further striking increase of tyrosinase activity and melanin formation, while treatment of serum containing cultures with Bu2cAMP and theophylline showed only a slight rise in melanogenesis. It is suggested that these stimulatory effects are mediated by an increased intracellular cAMP level, since a correlation between the degree of melanogenesis and cellular cAMP content was indicated. Treatment of serum-free or serum-containing cultures with the phosphodiesterase inhibitor theophylline (5X10(-4)--10(-3)M) alone revealed only a slight enhancement (about 20%) of melanogenesis. Because augmentation of melanogenesis by serum-free medium alone or together with Bu2cAMP and theophylline was prevented by cycloheximide (or actinomycin D), de novo protein synthesis seems to be required for these stimulatory effects.", "contents": "Stimulation of tyrosinase activity and melanin formation of cultured melanoma cells by serum deprivation alone or in combination with dibutyryl cyclic AMP and theophylline. Serum removal from the media of serial monolayer cultures of the Harding-Passey melanoma during an incubation period of 3 days resulted in an exponentially declining DNA synthesis rate (measured by the incorporation of [14C]thymidine) and in an inhibition of cell proliferation. Protein synthesis, as measured by the incorporation of radioactive leucine, was less affected than DNA synthesis. Incubation in serum-free culture medium resulted in significant rises of tyrosinase activity and cellular melanin content. Addition of dibutyryl adenosine 3':5' monophosphate (Bu2cAMP, 5X10(-4) M) and theophylline (5X10(-4) M) to serum-free cultures caused a further striking increase of tyrosinase activity and melanin formation, while treatment of serum containing cultures with Bu2cAMP and theophylline showed only a slight rise in melanogenesis. It is suggested that these stimulatory effects are mediated by an increased intracellular cAMP level, since a correlation between the degree of melanogenesis and cellular cAMP content was indicated. Treatment of serum-free or serum-containing cultures with the phosphodiesterase inhibitor theophylline (5X10(-4)--10(-3)M) alone revealed only a slight enhancement (about 20%) of melanogenesis. Because augmentation of melanogenesis by serum-free medium alone or together with Bu2cAMP and theophylline was prevented by cycloheximide (or actinomycin D), de novo protein synthesis seems to be required for these stimulatory effects."}
{"id": "PMID:198993", "title": "Enzymatic oxydation of linoleic acid: formation of bittertasting fatty acids.", "content": "Linoleic acid was oxidized with a protein fraction from soya beans (25 degrees C; 2h), in which lipoxygenase and peroxydase activities occurred. The fatty acids formed were isolated and, after emulsification with a sugar ester, were evaluated for bitter taste. The main components of the bitter-tasting fractions was a mixture of 9.12.13-trihydroxyoctadec-10- and 9.10.13-trihydroxyoctadec-11-enoic acids. The taste threshold lies in the range 0.6-0.9 mumol/ml. Two further trihydroxy-acids and two oxodihydroxy-acids were also identified in the bitter-tasting fraction.", "contents": "Enzymatic oxydation of linoleic acid: formation of bittertasting fatty acids. Linoleic acid was oxidized with a protein fraction from soya beans (25 degrees C; 2h), in which lipoxygenase and peroxydase activities occurred. The fatty acids formed were isolated and, after emulsification with a sugar ester, were evaluated for bitter taste. The main components of the bitter-tasting fractions was a mixture of 9.12.13-trihydroxyoctadec-10- and 9.10.13-trihydroxyoctadec-11-enoic acids. The taste threshold lies in the range 0.6-0.9 mumol/ml. Two further trihydroxy-acids and two oxodihydroxy-acids were also identified in the bitter-tasting fraction."}
{"id": "PMID:198994", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. IX. Influence of bivalent cations on the diphosphatase activity of muscle tissue].", "content": "The diphosphatase of comminuted muscle tissue is activated by high MgCl2 concentrations. CaCl2, EDTA and low concentrations of MgCl2 lower the activity. The addition of diphosphate inhibits even after its complete enzymatic hydrolysis the breakdown of additionally added diphosphate; addition of MgCl2 increases the diphosphatase activity again.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. IX. Influence of bivalent cations on the diphosphatase activity of muscle tissue]. The diphosphatase of comminuted muscle tissue is activated by high MgCl2 concentrations. CaCl2, EDTA and low concentrations of MgCl2 lower the activity. The addition of diphosphate inhibits even after its complete enzymatic hydrolysis the breakdown of additionally added diphosphate; addition of MgCl2 increases the diphosphatase activity again."}
{"id": "PMID:198995", "title": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. XII. Influence of the breakdown of tripolyphosphate and diphosphate on the water-holding-capacity of meat (author's transl)].", "content": "The increase in the water-holding capacity of salted minced bovine muscle caused by added diphosphate is maintained also after a complete enzymatic breakdown of the diphosphate. This effect is probably due to irreversible dissociation of actomyosin by DP in presence of NaCl.--An increase in water-holding capacity of minced salted bovine muscle after addition of tripolyphosphate occurs only if the tripolyphosphate is enzymatically hydrolysed to diphosphate. In contrast to diphosphate, tripolyphosphate apparently does not cause a dissociation of the actomyosin system.", "contents": "[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. XII. Influence of the breakdown of tripolyphosphate and diphosphate on the water-holding-capacity of meat (author's transl)]. The increase in the water-holding capacity of salted minced bovine muscle caused by added diphosphate is maintained also after a complete enzymatic breakdown of the diphosphate. This effect is probably due to irreversible dissociation of actomyosin by DP in presence of NaCl.--An increase in water-holding capacity of minced salted bovine muscle after addition of tripolyphosphate occurs only if the tripolyphosphate is enzymatically hydrolysed to diphosphate. In contrast to diphosphate, tripolyphosphate apparently does not cause a dissociation of the actomyosin system."}
{"id": "PMID:198990", "title": "Dissociation and reassociation of poliovirus. II. Protein components obtained by urea treatment of the virus particle.", "content": "Dissociation of poliovirus by 9 M urea in 0.015 M NaCl at 25 degrees C resulted in the liberation of 35S RNA and of polypeptides sedimenting at 2S in sucrose gradients containing 9 M urea. However, a ribonucleopolypeptide (RNPP) complex sedimenting at 45S and oligomers of the viral polypeptides sedimenting at 7--8S were found in addition to the monomers sedimenting at 2S when the urea concentration was lowered to 5 M after the dissociation procedure. Ribonuclease treatment prevents the appearance of the RNPP-complex. The amount of the RNPP-complex decreased, when the dissociation was performed at higher ionic strength. Under these conditions small amounts of empty capsids were detected. Polyacrylamide gel electrophoresis showed that the RNPP-complex contained the polypeptide VP1. The oligomers (7--8S) contained the polypeptide VP3 and small amounts of VP2. The bulk of VP2 and some VP3 were found in the 2S position together with VP4. The molecular weight of the dissociation products in urea and phosphate buffer was determined by gel filtration to be about 30,000 for the monomeric polypeptides containing predominantly VP2 and about 70,000 for the oligomeric polypeptides containing predominantly VP3. Our results demonstrate that the oligomers and the RNPP-complex are not primary products obtained by dissociation of the virus particle by urea but are due to a reassociation of the polypeptides or of VP1 and RNA.", "contents": "Dissociation and reassociation of poliovirus. II. Protein components obtained by urea treatment of the virus particle. Dissociation of poliovirus by 9 M urea in 0.015 M NaCl at 25 degrees C resulted in the liberation of 35S RNA and of polypeptides sedimenting at 2S in sucrose gradients containing 9 M urea. However, a ribonucleopolypeptide (RNPP) complex sedimenting at 45S and oligomers of the viral polypeptides sedimenting at 7--8S were found in addition to the monomers sedimenting at 2S when the urea concentration was lowered to 5 M after the dissociation procedure. Ribonuclease treatment prevents the appearance of the RNPP-complex. The amount of the RNPP-complex decreased, when the dissociation was performed at higher ionic strength. Under these conditions small amounts of empty capsids were detected. Polyacrylamide gel electrophoresis showed that the RNPP-complex contained the polypeptide VP1. The oligomers (7--8S) contained the polypeptide VP3 and small amounts of VP2. The bulk of VP2 and some VP3 were found in the 2S position together with VP4. The molecular weight of the dissociation products in urea and phosphate buffer was determined by gel filtration to be about 30,000 for the monomeric polypeptides containing predominantly VP2 and about 70,000 for the oligomeric polypeptides containing predominantly VP3. Our results demonstrate that the oligomers and the RNPP-complex are not primary products obtained by dissociation of the virus particle by urea but are due to a reassociation of the polypeptides or of VP1 and RNA."}
{"id": "PMID:198997", "title": "[The lymphocyte transformation test in squamous epithelial carcinomas of the orofacial region].", "content": "In the last years cell mediated immune reactions against the antigens of human carcinomas have obtained an increasing importance. With the lymphocyte transformation tests was found on the estimate of the PHA (phythemagglutinin)-stimulation a significant difference of the T-cell stimulation of patients with squamous cell carcinoma of the orofacial region opposite to a comparison group of healthy patients.", "contents": "[The lymphocyte transformation test in squamous epithelial carcinomas of the orofacial region]. In the last years cell mediated immune reactions against the antigens of human carcinomas have obtained an increasing importance. With the lymphocyte transformation tests was found on the estimate of the PHA (phythemagglutinin)-stimulation a significant difference of the T-cell stimulation of patients with squamous cell carcinoma of the orofacial region opposite to a comparison group of healthy patients."}
{"id": "PMID:198998", "title": "[Operative treatment of fractures of the patella (author's transl)].", "content": "Relative incongruance and great pressure in the femoro-patella joint are, besides the primary traumatic damage of the cartilage, responsible for frequent posttraumatic arthrosis and posttraumatic chondropathy of the patella after patellafracture. An operative reconstruction with a smooth joint surface of the patella is necessary. The only reliable method to fulfil these demands is the tension wire osteosynthesis by Pauwels, which, according to the type of fracture, can be combined with Kirschner wires and small fragment screws. The best access to the patella is established by diagonal incision. Open fractures must and closed fractures should be operated immediately. In comminuted fractures with devitalised cartilagefragments there is no indication to preserve the patella. Primary patellectomy has better results as late patellectomy. According to stability the after-treatment requires 4 to 6 weeks rest in a plaster cast. Although the operation can be performed with technical skill, arthrosis and chondropathy of the patella cannot always be avoided.", "contents": "[Operative treatment of fractures of the patella (author's transl)]. Relative incongruance and great pressure in the femoro-patella joint are, besides the primary traumatic damage of the cartilage, responsible for frequent posttraumatic arthrosis and posttraumatic chondropathy of the patella after patellafracture. An operative reconstruction with a smooth joint surface of the patella is necessary. The only reliable method to fulfil these demands is the tension wire osteosynthesis by Pauwels, which, according to the type of fracture, can be combined with Kirschner wires and small fragment screws. The best access to the patella is established by diagonal incision. Open fractures must and closed fractures should be operated immediately. In comminuted fractures with devitalised cartilagefragments there is no indication to preserve the patella. Primary patellectomy has better results as late patellectomy. According to stability the after-treatment requires 4 to 6 weeks rest in a plaster cast. Although the operation can be performed with technical skill, arthrosis and chondropathy of the patella cannot always be avoided."}
{"id": "PMID:198999", "title": "The portals of entry of herpes simplex virus infections.", "content": "In the present paper different possible portals of entry into the body for Herpes simplex Virus are examined. The possibility to infect the cornea with HsV without a preceding scarification was established. Scanning microscopy clearly showed the lesions of the infected cornea and a parallelity between the concentration of the inoculum and the spread of lesions. The i.c., i.m. and i.p. portals of entry are compared as to their capacity to produce encephalitis. The titration of virus may also be realized in the animal experiment. The intragastric portal of entry could be clearly demonstrated. So it is possible to explain herpes encephalitis in human newborns from mothers infected with Herpes virus.", "contents": "The portals of entry of herpes simplex virus infections. In the present paper different possible portals of entry into the body for Herpes simplex Virus are examined. The possibility to infect the cornea with HsV without a preceding scarification was established. Scanning microscopy clearly showed the lesions of the infected cornea and a parallelity between the concentration of the inoculum and the spread of lesions. The i.c., i.m. and i.p. portals of entry are compared as to their capacity to produce encephalitis. The titration of virus may also be realized in the animal experiment. The intragastric portal of entry could be clearly demonstrated. So it is possible to explain herpes encephalitis in human newborns from mothers infected with Herpes virus."}
{"id": "PMID:199000", "title": "[Detection of viruses in water of the Baltic Sea (author's transl)].", "content": "Virological examination of water of the Baltic Sea in the neighbourhood of a sewage outfall was done. By means of an apparatus for concentrating viruses in water, it was possible to detect enteroviruses in four of eleven samples, and in general in those moments, when conditions were fulfilled by a certain windway. The amount of viruses varied from 5 to 126 pfu in 10 liters, the ratio of virus to E. coli titer from 1:11 111 to 1:100 000. Factors influencing the decrease of virus titer in seawater were briefly discussed.", "contents": "[Detection of viruses in water of the Baltic Sea (author's transl)]. Virological examination of water of the Baltic Sea in the neighbourhood of a sewage outfall was done. By means of an apparatus for concentrating viruses in water, it was possible to detect enteroviruses in four of eleven samples, and in general in those moments, when conditions were fulfilled by a certain windway. The amount of viruses varied from 5 to 126 pfu in 10 liters, the ratio of virus to E. coli titer from 1:11 111 to 1:100 000. Factors influencing the decrease of virus titer in seawater were briefly discussed."}
{"id": "PMID:199001", "title": "Adenovirus infection in lambs. II. Experimental infection of lambs.", "content": "Adenovirus strain GY/14 isolated during a natural outbreak was used in experimental infection. Three weeks old lambs responded with temperature rise, respiratory symptoms and diarrhoea to the infection. Infection spread to a contact animal, too. Reisolation of the virus was successful from the nasal discharge and feces from the 3rd to 10th, and the 3rd to 5th day following infection, respectively. In the killed experimental animals the pathological and histological changes observed were similar to those observed in natural cases. On comparing the natural outbreaks with the experimental infection the only difference appeared in the severity of the changes. Following the experimental infection characteristic nuclear inclusions appeared in the nasal and bronchiolar epithelium, in the alveolar septal cells and in the reticular cells of the lymph nodes. Epizootiologic observations and experimental results confirm the assumption that our adenovirus strains isolated from natural cases are pathogenic for lambs.", "contents": "Adenovirus infection in lambs. II. Experimental infection of lambs. Adenovirus strain GY/14 isolated during a natural outbreak was used in experimental infection. Three weeks old lambs responded with temperature rise, respiratory symptoms and diarrhoea to the infection. Infection spread to a contact animal, too. Reisolation of the virus was successful from the nasal discharge and feces from the 3rd to 10th, and the 3rd to 5th day following infection, respectively. In the killed experimental animals the pathological and histological changes observed were similar to those observed in natural cases. On comparing the natural outbreaks with the experimental infection the only difference appeared in the severity of the changes. Following the experimental infection characteristic nuclear inclusions appeared in the nasal and bronchiolar epithelium, in the alveolar septal cells and in the reticular cells of the lymph nodes. Epizootiologic observations and experimental results confirm the assumption that our adenovirus strains isolated from natural cases are pathogenic for lambs."}
{"id": "PMID:199002", "title": "Experimental infection of calves with an adenovirus isolated from sheep and related to bovine Adenovirus type 2 I. Clinical and virological studies.", "content": "Colostrum deprived calves were experimentally infected with an adenovirus isolated from sheep and related to bovine adenovirus type 2. The calves showed respiratory symptoms and mild diarrhoea from the third day after infection. Laboratory tests revealed the development of leucopenia, lymphopenia, a drop of the pH of the urine and the appearance of pathological changes in the urine. The animals shed the virus in their nasal discharge, faeces and urine. Comparing the clinical and virological findings with the previous experimental infection of lambs it is concluded, that this type of adenovirus is similarly pathogenic for the two ruminant species.", "contents": "Experimental infection of calves with an adenovirus isolated from sheep and related to bovine Adenovirus type 2 I. Clinical and virological studies. Colostrum deprived calves were experimentally infected with an adenovirus isolated from sheep and related to bovine adenovirus type 2. The calves showed respiratory symptoms and mild diarrhoea from the third day after infection. Laboratory tests revealed the development of leucopenia, lymphopenia, a drop of the pH of the urine and the appearance of pathological changes in the urine. The animals shed the virus in their nasal discharge, faeces and urine. Comparing the clinical and virological findings with the previous experimental infection of lambs it is concluded, that this type of adenovirus is similarly pathogenic for the two ruminant species."}
{"id": "PMID:199005", "title": "Overlapping effects of different pituitary hormones on the oogenesis and spermatogenesis of Helix pomatia.", "content": "In agreement with earlier results, follicle stimulating hormone (FSH) enhances spermatogenesis in the snail. Thyreotropic hormone (TSH), which resembles FSH in its chemical structure, acts in the same way as does adrenocorticotropic hormone (ACTH) to a lesser extent. As opposed to FSH, TSH and ACTH clearly increased the number of mature egg cells. The experiments support the view that the gonad cells of the snails respond to vertebrate hormones, and that the hormones have overlapping effects at this level.", "contents": "Overlapping effects of different pituitary hormones on the oogenesis and spermatogenesis of Helix pomatia. In agreement with earlier results, follicle stimulating hormone (FSH) enhances spermatogenesis in the snail. Thyreotropic hormone (TSH), which resembles FSH in its chemical structure, acts in the same way as does adrenocorticotropic hormone (ACTH) to a lesser extent. As opposed to FSH, TSH and ACTH clearly increased the number of mature egg cells. The experiments support the view that the gonad cells of the snails respond to vertebrate hormones, and that the hormones have overlapping effects at this level."}
{"id": "PMID:199010", "title": "HCG-binding capacity of the rat ovary during pregnancy.", "content": "During pregnancy, binding of 125I-labelled HCG to the rat ovary increases markedly from the 3rd to the 17th day of pregnancy but is reduced drastically at the end of pregnancy and after delivery. At the 17th day of pregnancy the HCG-binding capacity of the rat ovary is raised 76-fold in comparison to oestrous rats (17th day of pregnancy: 128 X 10(-15) mol/mg wet weight; oestrus: 1.67 X 10(-15) mol/mg wet weight). It is assumed that only LH receptors not occupied by endogenous hormone are covered by our assay. The high number of \"free\" ovarian HCG receptors during pregnancy apparently represents \"Spare\" receptors, the functional significance of which remains unclear. It is suggested that the metabolic activity of the ovarian luteal cells during pregnancy is not restricted by the number of HCG receptors present, but through the level of the endogenous gonadotrophic hormone and/or some unknown factors residing in the luteal cell.", "contents": "HCG-binding capacity of the rat ovary during pregnancy. During pregnancy, binding of 125I-labelled HCG to the rat ovary increases markedly from the 3rd to the 17th day of pregnancy but is reduced drastically at the end of pregnancy and after delivery. At the 17th day of pregnancy the HCG-binding capacity of the rat ovary is raised 76-fold in comparison to oestrous rats (17th day of pregnancy: 128 X 10(-15) mol/mg wet weight; oestrus: 1.67 X 10(-15) mol/mg wet weight). It is assumed that only LH receptors not occupied by endogenous hormone are covered by our assay. The high number of \"free\" ovarian HCG receptors during pregnancy apparently represents \"Spare\" receptors, the functional significance of which remains unclear. It is suggested that the metabolic activity of the ovarian luteal cells during pregnancy is not restricted by the number of HCG receptors present, but through the level of the endogenous gonadotrophic hormone and/or some unknown factors residing in the luteal cell."}
{"id": "PMID:199013", "title": "Inhibition by somatostatin of mouse thyroid activity following stimulation by thyrotrophin, isoprenaline and dibutyryl cyclic-AMP.", "content": "The recent discovery of somatostatin-containing cells within the thyroid gland infers that somatostatin may influence thyroid activity. This possibility was investigated by measurements of radio-iodine release in mice pre-treated with 125I and T4. The animals were treated with TSH, isoprenaline or dibutyryl-cyclic AMP with and without concomitant injection of somatostatin. It was found that somatostatin reduced the blood 125I increase in response to each of the three thyroid-stimulating agents. The elimination rates of 125I-labelled T4 and T3 were unaffected by somatostatin. The observations suggests that somatostatin may participate in the regulation of thyroid hormone secretion, by an inhibitory effect exerted within the thyroid gland.", "contents": "Inhibition by somatostatin of mouse thyroid activity following stimulation by thyrotrophin, isoprenaline and dibutyryl cyclic-AMP. The recent discovery of somatostatin-containing cells within the thyroid gland infers that somatostatin may influence thyroid activity. This possibility was investigated by measurements of radio-iodine release in mice pre-treated with 125I and T4. The animals were treated with TSH, isoprenaline or dibutyryl-cyclic AMP with and without concomitant injection of somatostatin. It was found that somatostatin reduced the blood 125I increase in response to each of the three thyroid-stimulating agents. The elimination rates of 125I-labelled T4 and T3 were unaffected by somatostatin. The observations suggests that somatostatin may participate in the regulation of thyroid hormone secretion, by an inhibitory effect exerted within the thyroid gland."}
{"id": "PMID:199007", "title": "Comparative investigations on cytochemical and cytohormonal exponents of estrogens- progesteron activity in vaginal epithelium in women with complicated pregnancy. I. Threatened abortion.", "content": "Cytohormonal smears taken from the women hospitalized due to threatened abortion were classified in four groups according to KPI, E.I., FI and CI values. Simultaneously in the vaginal section hormono-dependent enzymes (Al.,P.,Ac.,P., NADH2 t.r., ATP-ase, PAS reaction for glycogen) were studied. The investigated enzymes were compared with the values of cytohormonal indices, in intensity of cytochemical reaction. A distinct correlation was discovered between the intensity of the reactions for Al.,P.,ATP-ase and NADH2 t.r. and KPI, as well as for EI values which suggest either the balance of estrogens-progesteron or its disturbance.", "contents": "Comparative investigations on cytochemical and cytohormonal exponents of estrogens- progesteron activity in vaginal epithelium in women with complicated pregnancy. I. Threatened abortion. Cytohormonal smears taken from the women hospitalized due to threatened abortion were classified in four groups according to KPI, E.I., FI and CI values. Simultaneously in the vaginal section hormono-dependent enzymes (Al.,P.,Ac.,P., NADH2 t.r., ATP-ase, PAS reaction for glycogen) were studied. The investigated enzymes were compared with the values of cytohormonal indices, in intensity of cytochemical reaction. A distinct correlation was discovered between the intensity of the reactions for Al.,P.,ATP-ase and NADH2 t.r. and KPI, as well as for EI values which suggest either the balance of estrogens-progesteron or its disturbance."}
{"id": "PMID:199014", "title": "Islet contents of cyclic 3',5'-guanosine monophosphate under conditions which affect the cyclic 3',5'-adenosine monophosphate.", "content": "The sensitivity of the radioimmunoassay for cGMP was considerably increased by previous 2'-O-succinylation of the nucleotide. The basal content of cGMP in beta-cell-rich pancreatic islets isolated from ob/ob-mice was similar to that of cAMP, i.e. about 3 mumoles per kg dry weight. Extra-cellular Ca2+ was a prerequisite for maintaining this amount of cGMP. The islet cGMP differed from cAMP in being only slightly enhanced or not affected at all when the islets were exposed to high concentrations of glucose, the sulphydryl reagents chloromercuribenzene-p-sulphonic acid and iodoacetamide, or the potent phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine. The data obtained suggest that the turnover rate for cGMP is much slower than that for cAMP in the pancreatic beta-cells. The interrelationships between the two cyclic nucleotides do not seem to fit into a simple pattern of antagonism.", "contents": "Islet contents of cyclic 3',5'-guanosine monophosphate under conditions which affect the cyclic 3',5'-adenosine monophosphate. The sensitivity of the radioimmunoassay for cGMP was considerably increased by previous 2'-O-succinylation of the nucleotide. The basal content of cGMP in beta-cell-rich pancreatic islets isolated from ob/ob-mice was similar to that of cAMP, i.e. about 3 mumoles per kg dry weight. Extra-cellular Ca2+ was a prerequisite for maintaining this amount of cGMP. The islet cGMP differed from cAMP in being only slightly enhanced or not affected at all when the islets were exposed to high concentrations of glucose, the sulphydryl reagents chloromercuribenzene-p-sulphonic acid and iodoacetamide, or the potent phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine. The data obtained suggest that the turnover rate for cGMP is much slower than that for cAMP in the pancreatic beta-cells. The interrelationships between the two cyclic nucleotides do not seem to fit into a simple pattern of antagonism."}
{"id": "PMID:199015", "title": "In vitro responses of focal hyperplastic tissue of the human adrenal zona fasciculata to ACTH.", "content": "The temporal cAMP, cortisol and aldosterone responses to ACTH of focal hyperplasia of the zona fasciculata and of normal human adrenocortical tissue were investigated. ACTH significantly increased cAMP levels (1 min) and cortisol output (2 min) in normal adrenal tissue but not in hyperplastic tissue. However, following ACTH treatment cortisol and aldosterone production were depressed in the abnormal adrenal tissue below the untreated or the ACTH stimulated normal adrenal tissue. In addition, basal cortisol and aldosterone production of the hyperplastic adrenal tissue was elevated above that of the normal adrenal tissue. These findings suggest that the cAMP second messenger concept may be only one of several mechanisms in the modulation of human adrenocortical function.", "contents": "In vitro responses of focal hyperplastic tissue of the human adrenal zona fasciculata to ACTH. The temporal cAMP, cortisol and aldosterone responses to ACTH of focal hyperplasia of the zona fasciculata and of normal human adrenocortical tissue were investigated. ACTH significantly increased cAMP levels (1 min) and cortisol output (2 min) in normal adrenal tissue but not in hyperplastic tissue. However, following ACTH treatment cortisol and aldosterone production were depressed in the abnormal adrenal tissue below the untreated or the ACTH stimulated normal adrenal tissue. In addition, basal cortisol and aldosterone production of the hyperplastic adrenal tissue was elevated above that of the normal adrenal tissue. These findings suggest that the cAMP second messenger concept may be only one of several mechanisms in the modulation of human adrenocortical function."}
{"id": "PMID:199018", "title": "Biochemical studies on the leukocytes in Chediak-Higashi syndrome.", "content": "Blood leukocytes from a patient with Chediak-Higashi syndrome (CHS) were compared with normal cells for their capacity of extruding (exocytosis) the lysosomal enzyme myeloperoxidase during phagocytosis or after a treatment with the ionophore A23187 and Ca2+. A decreased rate and extent of exocytosis in phagocytizing CHS cells was observed also with the Ca2+ ionophore. This suggests that a defect in Ca2+ mobilization is not responsible for the impaired secretion of granule content. Isolated granules of CHS cells and of leukocytes were treated with the detergent Triton X-100. Since the solubilization of myeloperoxidase from the CHS granules was much lower than from the normal ones, we suggest that the former organelles have a more resistant membrane.", "contents": "Biochemical studies on the leukocytes in Chediak-Higashi syndrome. Blood leukocytes from a patient with Chediak-Higashi syndrome (CHS) were compared with normal cells for their capacity of extruding (exocytosis) the lysosomal enzyme myeloperoxidase during phagocytosis or after a treatment with the ionophore A23187 and Ca2+. A decreased rate and extent of exocytosis in phagocytizing CHS cells was observed also with the Ca2+ ionophore. This suggests that a defect in Ca2+ mobilization is not responsible for the impaired secretion of granule content. Isolated granules of CHS cells and of leukocytes were treated with the detergent Triton X-100. Since the solubilization of myeloperoxidase from the CHS granules was much lower than from the normal ones, we suggest that the former organelles have a more resistant membrane."}
{"id": "PMID:199019", "title": "Coupling of fibrin with low density lipoproteins.", "content": "By means of chemical methods and immunodiffusion technique it has been shown that low density lipoproteins incorporate into the structure of fibrin clot formed both in purified systems and in the blood plasma. Quantity of the incorporated lipoproteins into the fibrin depends on the concentration of fibrinogen and low density lipoproteins in the blood plasma. Rinsing of the fibrin with solutions of chemical compounds destroying different types of binding show that low density lipoproteins couple with the fibrin clot by means of ion and hydrogen bindings.", "contents": "Coupling of fibrin with low density lipoproteins. By means of chemical methods and immunodiffusion technique it has been shown that low density lipoproteins incorporate into the structure of fibrin clot formed both in purified systems and in the blood plasma. Quantity of the incorporated lipoproteins into the fibrin depends on the concentration of fibrinogen and low density lipoproteins in the blood plasma. Rinsing of the fibrin with solutions of chemical compounds destroying different types of binding show that low density lipoproteins couple with the fibrin clot by means of ion and hydrogen bindings."}
{"id": "PMID:199029", "title": "Herpes simplex virus-IgM specific antibodies in Guillain-Barr\u00e9 syndrome and encephalitis.", "content": "Herpes simplex virus (HSV) has veen associated with a variety of inflammatory neurologic disorders. Recently we studied a patient with Guillain-Barr\u00e9 syndrome (GBS) following acute herpes vaginalis infection. Since IgM virus-specific antibody is thought to be a reliable indicator of acute viral infection, we employed a 2-h serologic assay for serum IgM antibodies to HSV using an indirect immunofluorescent technique. This patient demonstrated high serum IgM titers to HSV type 2 during the acute phase of her neurologic syndrome. The titer dropped substantially as convalescence progressed. A search for similar elevations in HSV-IgM specific antibody was made on sera from more than 70 other GBS patients. No other significant IgM antibody titers to either HSV type 1 or type 2 were found in this GBS series and a large number of neurologic controls. However, sera from two patients with a presumptive diagnosis of acute herpes encephalitis based on clinical and cerebrospinal fluid findings were positive, showing high titers in our test. The results of this study suggest that associated acute HSV infection is uncommon in GBS and an immunofluorescent seroassay of the type reported here may be a valuable noninvasive technique enabling the clinical laboratory to rapid confirm a diagnosis of herpes encephalitis.", "contents": "Herpes simplex virus-IgM specific antibodies in Guillain-Barr\u00e9 syndrome and encephalitis. Herpes simplex virus (HSV) has veen associated with a variety of inflammatory neurologic disorders. Recently we studied a patient with Guillain-Barr\u00e9 syndrome (GBS) following acute herpes vaginalis infection. Since IgM virus-specific antibody is thought to be a reliable indicator of acute viral infection, we employed a 2-h serologic assay for serum IgM antibodies to HSV using an indirect immunofluorescent technique. This patient demonstrated high serum IgM titers to HSV type 2 during the acute phase of her neurologic syndrome. The titer dropped substantially as convalescence progressed. A search for similar elevations in HSV-IgM specific antibody was made on sera from more than 70 other GBS patients. No other significant IgM antibody titers to either HSV type 1 or type 2 were found in this GBS series and a large number of neurologic controls. However, sera from two patients with a presumptive diagnosis of acute herpes encephalitis based on clinical and cerebrospinal fluid findings were positive, showing high titers in our test. The results of this study suggest that associated acute HSV infection is uncommon in GBS and an immunofluorescent seroassay of the type reported here may be a valuable noninvasive technique enabling the clinical laboratory to rapid confirm a diagnosis of herpes encephalitis."}
{"id": "PMID:199030", "title": "Fine structural changes in the mutant hamster with hind leg paralysis.", "content": "Various parts of the central and peripheral nervous system of the mutant hamster with hind leg paralysis were studied in the electron microscope. A number of alterations involving the myelin sheath, the axon and certain neuronal perikarya were observed. Anterior horn cells were apparently well preserved. This condition represents an inherited form of peripheral neuropathy.", "contents": "Fine structural changes in the mutant hamster with hind leg paralysis. Various parts of the central and peripheral nervous system of the mutant hamster with hind leg paralysis were studied in the electron microscope. A number of alterations involving the myelin sheath, the axon and certain neuronal perikarya were observed. Anterior horn cells were apparently well preserved. This condition represents an inherited form of peripheral neuropathy."}
{"id": "PMID:199031", "title": "Comparative ultrastructural observations on peripheral nerve abnormalities in the late infantile, juvenile and late onset forms of metachromatic leukodystrophy.", "content": "The ultrastructural findings in nerve biopsies from two cases of late onset metachromatic leukodystrophy were compared with those in cases of late infantile and juvenile onset. Hypertrophic changes and regenerating clusters were more evident in the late onset cases, in which macrophages were less frequent, presumably reflecting the chronicity of the disorder in this form. Inclusions within Schwann cells and endoneurial macrophages were similar in all four cases. Myelin figures, in which the periodicity of major dense lines was 8 nm, were present in Schwann cells associated with myelinated axons. The electron lucent zones between the major dense lines were bisected by lines of lesser electron density. These inclusions were probably related to myelin breakdown. All other inclusions displayed a periodicity of 5.8 nm and consisted of zebra bodies, vacuoles containing irregularly orientated lamellar material and stacks of flattened discs. These inclusions represented the metachromatic sulphatide deposits. Occasional inclusion bodies were observed within axons.", "contents": "Comparative ultrastructural observations on peripheral nerve abnormalities in the late infantile, juvenile and late onset forms of metachromatic leukodystrophy. The ultrastructural findings in nerve biopsies from two cases of late onset metachromatic leukodystrophy were compared with those in cases of late infantile and juvenile onset. Hypertrophic changes and regenerating clusters were more evident in the late onset cases, in which macrophages were less frequent, presumably reflecting the chronicity of the disorder in this form. Inclusions within Schwann cells and endoneurial macrophages were similar in all four cases. Myelin figures, in which the periodicity of major dense lines was 8 nm, were present in Schwann cells associated with myelinated axons. The electron lucent zones between the major dense lines were bisected by lines of lesser electron density. These inclusions were probably related to myelin breakdown. All other inclusions displayed a periodicity of 5.8 nm and consisted of zebra bodies, vacuoles containing irregularly orientated lamellar material and stacks of flattened discs. These inclusions represented the metachromatic sulphatide deposits. Occasional inclusion bodies were observed within axons."}
{"id": "PMID:199032", "title": "Giant axonal neuropathy. Involvement of peripheral nerve, myenteric plexus and extra-neuronal area.", "content": "A case of giant axonal neuropathy in a 8 years old child is reported by light and electron microscopy. Clinically, this case is strikingly similar to the rare previous reports and characterized by a distal neuropathy, CNS symptoms and tightly curled hair. Giant axons were found in the sural nerve but had been absent at the onset of the illness. An increase in the number of neurofilaments was found in the axons and neurons of the myenteric plexus. The number of microfilaments was also increased in various types of cells namely Schwann and endothelial cells and fibroblasts: This suggests that the metabolic disorder, probably inborn and genetic, does not only affect the nervous system.", "contents": "Giant axonal neuropathy. Involvement of peripheral nerve, myenteric plexus and extra-neuronal area. A case of giant axonal neuropathy in a 8 years old child is reported by light and electron microscopy. Clinically, this case is strikingly similar to the rare previous reports and characterized by a distal neuropathy, CNS symptoms and tightly curled hair. Giant axons were found in the sural nerve but had been absent at the onset of the illness. An increase in the number of neurofilaments was found in the axons and neurons of the myenteric plexus. The number of microfilaments was also increased in various types of cells namely Schwann and endothelial cells and fibroblasts: This suggests that the metabolic disorder, probably inborn and genetic, does not only affect the nervous system."}
{"id": "PMID:199034", "title": "The role of the subependymal plate in glial tumorigenesis.", "content": "We have studied the sequential morphological events of glial tumorigenesis in neonatal dogs, using high titer subgroup C Bratislava-77 Avian Sarcoma Virus, given as 0.01 ml by intraventricular inoculation. The cells of the subependymal plate are those which seem to form the gliomas; cytoplasmic alterations are evident within 24 h after inoculation and microfoci of gliomas, contiguous with the subependymal plate of the lateral ventricles, are visible within 7 days. Independent tumors are present by the 10th post-inoculation day. These studies support the hypothesis of Globus and Kuhlenbeck, which implicates the cells of the subependymal palte in glial tumorigenesis.", "contents": "The role of the subependymal plate in glial tumorigenesis. We have studied the sequential morphological events of glial tumorigenesis in neonatal dogs, using high titer subgroup C Bratislava-77 Avian Sarcoma Virus, given as 0.01 ml by intraventricular inoculation. The cells of the subependymal plate are those which seem to form the gliomas; cytoplasmic alterations are evident within 24 h after inoculation and microfoci of gliomas, contiguous with the subependymal plate of the lateral ventricles, are visible within 7 days. Independent tumors are present by the 10th post-inoculation day. These studies support the hypothesis of Globus and Kuhlenbeck, which implicates the cells of the subependymal palte in glial tumorigenesis."}
{"id": "PMID:199035", "title": "Giant axonal neuropathy: possibly secondary to vitamin b12 malabsorption.", "content": "A giant axonal neuropathy is described in an adult with no evidence of a childhood onset of his disease and no history of exposure to toxic hydrocarbons. A causal relation to vitamin B12 malabsorption is proposed. This case suggests the need to expand the spectrum of diagnoses that must be considered when giant axons are encountered in peripheral nerve biopsy specimens.", "contents": "Giant axonal neuropathy: possibly secondary to vitamin b12 malabsorption. A giant axonal neuropathy is described in an adult with no evidence of a childhood onset of his disease and no history of exposure to toxic hydrocarbons. A causal relation to vitamin B12 malabsorption is proposed. This case suggests the need to expand the spectrum of diagnoses that must be considered when giant axons are encountered in peripheral nerve biopsy specimens."}
{"id": "PMID:199036", "title": "Herpes simplex encephalitis: an autopsy case with isolation of type 1 herpes simplex virus.", "content": "An adult case of herpes simplex encephalitis was studied after autopsy. Postmortem examination revealed necrotizing encephalitis associated with Cowdry type A intranuclear inclusion bodies in glial cells. Herper simplex virus type 1 was isolated from the removed brain. Herpes simplex virus antigens were detected diffusely in wide areas of the brain by immunofluorescent test and viral particles characteristic to herpes simplex virus were demonstrated by electron microscopy. There was an apparent discrepancy between severity of histological changes and distribution of virus antigen.", "contents": "Herpes simplex encephalitis: an autopsy case with isolation of type 1 herpes simplex virus. An adult case of herpes simplex encephalitis was studied after autopsy. Postmortem examination revealed necrotizing encephalitis associated with Cowdry type A intranuclear inclusion bodies in glial cells. Herper simplex virus type 1 was isolated from the removed brain. Herpes simplex virus antigens were detected diffusely in wide areas of the brain by immunofluorescent test and viral particles characteristic to herpes simplex virus were demonstrated by electron microscopy. There was an apparent discrepancy between severity of histological changes and distribution of virus antigen."}
{"id": "PMID:199037", "title": "Bioavailability of natural estrogens in young females with secondary amenorrhea.", "content": "The bioavailability of 17 beta-estradiol valerate, free 17 beta-estradiol and Premarin was studied in 24 subjects suffering from secondary amenorrhea. 17 beta-estradiol and estrone were determined by specific radioimmunoassay systems. All estrogens were administered as single oral doses. The amounts applied were 2 and 10 mg of 17 beta-estradiol valerate or equivalent amounts of the free estradiol and Premarin, respectively. No elevations of 17 beta-estradiol serum levels were recorded at the lower dosages, whereas the increases of estrone serum levels were approximately tenfold over basal levels. Similar data were recorded in a group of 3 women with normal cycles after the ingestion of 2 mg of 17 beta-estradiol valerate. All subjects responded to the higher doses of estrogens with a moderate increase of 17 beta-estradiol serum levels, but with much higher elevation of estrone levels. These data suggest a rapid conversion of 17 beta-estradiol into estrone. The biological activity of 2 mg 17 beta-estradiol valerate is discussed on grounds of a possible metabolism of estrone sulfate at the target tissues.", "contents": "Bioavailability of natural estrogens in young females with secondary amenorrhea. The bioavailability of 17 beta-estradiol valerate, free 17 beta-estradiol and Premarin was studied in 24 subjects suffering from secondary amenorrhea. 17 beta-estradiol and estrone were determined by specific radioimmunoassay systems. All estrogens were administered as single oral doses. The amounts applied were 2 and 10 mg of 17 beta-estradiol valerate or equivalent amounts of the free estradiol and Premarin, respectively. No elevations of 17 beta-estradiol serum levels were recorded at the lower dosages, whereas the increases of estrone serum levels were approximately tenfold over basal levels. Similar data were recorded in a group of 3 women with normal cycles after the ingestion of 2 mg of 17 beta-estradiol valerate. All subjects responded to the higher doses of estrogens with a moderate increase of 17 beta-estradiol serum levels, but with much higher elevation of estrone levels. These data suggest a rapid conversion of 17 beta-estradiol into estrone. The biological activity of 2 mg 17 beta-estradiol valerate is discussed on grounds of a possible metabolism of estrone sulfate at the target tissues."}
{"id": "PMID:199042", "title": "Effects of exogenous ACTH on the rat fetal adrenal cortex: a histochemical and electron-microscopical observation.", "content": "ACTH was administered subcutaneously to rat fetus directly at the late stage of fetal development and acute reaction on the fetal adrenal cortex was observed histochemically and electron microscopically. By administration of ACTH the adrenal cortex became remarkably hyperemic and there were swollen cells in all layers, particularly in the middle and inner layers (corresponding to the zona fasciculata and reticularis in adult rat). Marked reduction of lipid, enlarged mitochondria with increased vesicular cristae and increased smooth-surfaced endoplasmic reticulum (SER) were characteristic. The alterations of mitochondria preceded the change of SER, and thereafter mitochondria showed rapid degeneration. The outer layer (corresponding to the zona glomerulosa in adult rat) also showed similar changes by ACTH to those of the other two layers. These results indicated that the fetal adrenal cortex of rats was exogenous ACTH-reactive and its reaction which was different from that of adult cortical cells, seemed to be specifically related to the development and differentiation of the cells.", "contents": "Effects of exogenous ACTH on the rat fetal adrenal cortex: a histochemical and electron-microscopical observation. ACTH was administered subcutaneously to rat fetus directly at the late stage of fetal development and acute reaction on the fetal adrenal cortex was observed histochemically and electron microscopically. By administration of ACTH the adrenal cortex became remarkably hyperemic and there were swollen cells in all layers, particularly in the middle and inner layers (corresponding to the zona fasciculata and reticularis in adult rat). Marked reduction of lipid, enlarged mitochondria with increased vesicular cristae and increased smooth-surfaced endoplasmic reticulum (SER) were characteristic. The alterations of mitochondria preceded the change of SER, and thereafter mitochondria showed rapid degeneration. The outer layer (corresponding to the zona glomerulosa in adult rat) also showed similar changes by ACTH to those of the other two layers. These results indicated that the fetal adrenal cortex of rats was exogenous ACTH-reactive and its reaction which was different from that of adult cortical cells, seemed to be specifically related to the development and differentiation of the cells."}
{"id": "PMID:199043", "title": "Functional prenatal development of anencephalic and normal anterior pituitary glands. In human and experimental animals studied by peroxidase-labeled antibody method.", "content": "In order to investigate the influence of the central nervous system on the functional differentiation of the fetal anterior pituitary gland, the pituitary gland of anencephalic and normal fetus was studied by the peroxidase-labeled antibody method for the localization of various hormones. The only abnormality of pituitary endocrine cells in anencephaly was a marked decrease of ACTH cells. In the normal development, ACTH appeared as the earliest hormone in 5 weeks. And all other hormones were seen in 13 weeks. The reason for the decrease of ACTH cells in anencephaly was speculated to be a suppression at an early developmental life. The experimental observations done in rats using MAM might support this speculation. The adrenal glands of anencephalus showed atrophy of the fetal cortex which was considered to correlate with the decrease in number of ACTH cells. Absence of the histochemical activity of alkaline phosphatase in the permanent cortex of anencephaly may indicate absence or inadequate stimulation by fetal ACTH. Further experimental studies in suppression of the central nervous system in early developmental life seemed to confirm the above speculation in functional differentiation of the fetal pituitary and adrenal glands.", "contents": "Functional prenatal development of anencephalic and normal anterior pituitary glands. In human and experimental animals studied by peroxidase-labeled antibody method. In order to investigate the influence of the central nervous system on the functional differentiation of the fetal anterior pituitary gland, the pituitary gland of anencephalic and normal fetus was studied by the peroxidase-labeled antibody method for the localization of various hormones. The only abnormality of pituitary endocrine cells in anencephaly was a marked decrease of ACTH cells. In the normal development, ACTH appeared as the earliest hormone in 5 weeks. And all other hormones were seen in 13 weeks. The reason for the decrease of ACTH cells in anencephaly was speculated to be a suppression at an early developmental life. The experimental observations done in rats using MAM might support this speculation. The adrenal glands of anencephalus showed atrophy of the fetal cortex which was considered to correlate with the decrease in number of ACTH cells. Absence of the histochemical activity of alkaline phosphatase in the permanent cortex of anencephaly may indicate absence or inadequate stimulation by fetal ACTH. Further experimental studies in suppression of the central nervous system in early developmental life seemed to confirm the above speculation in functional differentiation of the fetal pituitary and adrenal glands."}
{"id": "PMID:199040", "title": "Penetration of erythromycin stearate into maxillary sinus mucosa and secretion in chronic maxillary sinusitis.", "content": "The penetration of oral erythromycin stearate (Abboticin), administered in a dosage of 500 mg three times a day, into the maxillary sinus mucosa and secretion was studied in 15 patients (22 sinuses) operated on for chronic maxillary sinusitis. The average concentration in serum was 2.3 microgram/ml, 1.2 microgram/ml in secretion, and 1.8 microgram/ml in  mucosa. These concentrations are highly effective against diplococci and most aerobic and anaerobic streptococci (MIC value 0.06 microgram/ml) but not against Haemophilus influenzae (MIC value for 80% of 2 microgram/ml).", "contents": "Penetration of erythromycin stearate into maxillary sinus mucosa and secretion in chronic maxillary sinusitis. The penetration of oral erythromycin stearate (Abboticin), administered in a dosage of 500 mg three times a day, into the maxillary sinus mucosa and secretion was studied in 15 patients (22 sinuses) operated on for chronic maxillary sinusitis. The average concentration in serum was 2.3 microgram/ml, 1.2 microgram/ml in secretion, and 1.8 microgram/ml in  mucosa. These concentrations are highly effective against diplococci and most aerobic and anaerobic streptococci (MIC value 0.06 microgram/ml) but not against Haemophilus influenzae (MIC value for 80% of 2 microgram/ml)."}
{"id": "PMID:199044", "title": "Glomus tumor of the stomach. Light and electron microscopic study with literature review of related tumors.", "content": "A gastric tumor from a 27-year-old female showed the light microscopic features of glomus tumor. Ultrastructurally there were two types of tumor cells, i.e. smooth muscle and possible pericytes. From the literature review of ultrastructure of glomus tumor, hemangiopericytomas (HPC), leiomyoblastomas and leiomyomas, the glomus tumor appeared to exist as an intermediate form between HPC and leiomyomas which were considered to be in a broad spectrum of smooth muscle tumors.", "contents": "Glomus tumor of the stomach. Light and electron microscopic study with literature review of related tumors. A gastric tumor from a 27-year-old female showed the light microscopic features of glomus tumor. Ultrastructurally there were two types of tumor cells, i.e. smooth muscle and possible pericytes. From the literature review of ultrastructure of glomus tumor, hemangiopericytomas (HPC), leiomyoblastomas and leiomyomas, the glomus tumor appeared to exist as an intermediate form between HPC and leiomyomas which were considered to be in a broad spectrum of smooth muscle tumors."}
{"id": "PMID:199045", "title": "Skeletal muscle fibres and muscle enzyme activities in monozygous and dizygous twins of both sexes.", "content": "Significance of the genetic component in determining the interindividual variation observed in skeletal muscle fibre composition and enzyme activities was investigated in 31 pairs of male and female monozygous (MZ) and dizygous (DZ) twins, whose ages ranged in all but one pair (11 years) from 15 to 24 years. Percent distribution of slow twitch muscle fibres and activities of Ca2+ and Ng2+ stimulated ATPases, creatine phosphokinase, myokinase, phosphorylase, lactate dehydrogenase (LDH) and distribution of its isozyme LDH-1 were all analyzed in biopsy samples taken from the vastus lateralis muscle. The data disclosed that in contrast to DZ twins the MZ twins of both sexes had an essentially identical muscle fibre composition. Calculation of the heritability estimate for this parameter gave the values of 99.5% and 92.8%, respectively for males and females. In contrast to the fibre composition presence of a significant genetic component was not observed in any of the enzyme activities studied. It was concluded that there is a predominant genetic influence on the skeletal muscle fibre composition in man, and thus also on the potential capacity of the muscles to perform work.", "contents": "Skeletal muscle fibres and muscle enzyme activities in monozygous and dizygous twins of both sexes. Significance of the genetic component in determining the interindividual variation observed in skeletal muscle fibre composition and enzyme activities was investigated in 31 pairs of male and female monozygous (MZ) and dizygous (DZ) twins, whose ages ranged in all but one pair (11 years) from 15 to 24 years. Percent distribution of slow twitch muscle fibres and activities of Ca2+ and Ng2+ stimulated ATPases, creatine phosphokinase, myokinase, phosphorylase, lactate dehydrogenase (LDH) and distribution of its isozyme LDH-1 were all analyzed in biopsy samples taken from the vastus lateralis muscle. The data disclosed that in contrast to DZ twins the MZ twins of both sexes had an essentially identical muscle fibre composition. Calculation of the heritability estimate for this parameter gave the values of 99.5% and 92.8%, respectively for males and females. In contrast to the fibre composition presence of a significant genetic component was not observed in any of the enzyme activities studied. It was concluded that there is a predominant genetic influence on the skeletal muscle fibre composition in man, and thus also on the potential capacity of the muscles to perform work."}
{"id": "PMID:199047", "title": "Adenosine in rat cerebral cortex: its determination, normal values, and correlation to AMP and cyclic AMP during shortlasting ischemia.", "content": "It has recently been suggested that adenosine is a metabolic coupling factor responsible for an increased cerebral blood flow during hypoxia or increased functional activity. However, tissue adenosine concentrations have been reported to increase in situations previously shown to be unassociated with changes in tissue AMP concentrations. The present experiments were undertaken to assess cerebral cortex concentrations of adenosine under normal circumstances, and to relate changes in adenosine, AMP and cyclic AMP during shortlasting ischemia. Following freezing and extraction of tissue, adenosine was measured using high pressure liquid chromatography. In paralyzed and anaesthetized (70% N2O) rats, freezing of tissue through intact skull bone gave an adenosine concentration of 0.9 +/- 0.1 mumol-kg-1 (mean +/- S.E.M.). With freezing through the exposed dura the concentration was 3 times as high with a large scatter. When special precautions were taken to avoid tissue trauma during craniotomy, the adenosine concentration was 1.1 +/- 0.1 mumol-kg-1. It is concluded that previously reported values are erroneously high. During the first 60 s of total ischemia there was a linear correlation between increase in AMP and in adenosine concentration (as well as between adenosine and cyclic AMP concentrations). It is concluded that increases in tissue adenosine concentration only occur if AMP accumulates. However, since (relative) changes in adenosine concentrations are at least twice those of AMP, analyses of adenosine may provide sensitive measures of a change in phosphorylation state.", "contents": "Adenosine in rat cerebral cortex: its determination, normal values, and correlation to AMP and cyclic AMP during shortlasting ischemia. It has recently been suggested that adenosine is a metabolic coupling factor responsible for an increased cerebral blood flow during hypoxia or increased functional activity. However, tissue adenosine concentrations have been reported to increase in situations previously shown to be unassociated with changes in tissue AMP concentrations. The present experiments were undertaken to assess cerebral cortex concentrations of adenosine under normal circumstances, and to relate changes in adenosine, AMP and cyclic AMP during shortlasting ischemia. Following freezing and extraction of tissue, adenosine was measured using high pressure liquid chromatography. In paralyzed and anaesthetized (70% N2O) rats, freezing of tissue through intact skull bone gave an adenosine concentration of 0.9 +/- 0.1 mumol-kg-1 (mean +/- S.E.M.). With freezing through the exposed dura the concentration was 3 times as high with a large scatter. When special precautions were taken to avoid tissue trauma during craniotomy, the adenosine concentration was 1.1 +/- 0.1 mumol-kg-1. It is concluded that previously reported values are erroneously high. During the first 60 s of total ischemia there was a linear correlation between increase in AMP and in adenosine concentration (as well as between adenosine and cyclic AMP concentrations). It is concluded that increases in tissue adenosine concentration only occur if AMP accumulates. However, since (relative) changes in adenosine concentrations are at least twice those of AMP, analyses of adenosine may provide sensitive measures of a change in phosphorylation state."}
{"id": "PMID:199049", "title": "The adrenocortical response to angiotensin II infusion in anephric and non-nephrectomized patients on regular hemodialysis.", "content": "In the present study 8 anephric and 4 non-nephrectomized patients were stimulated with angiotensin II (A-II). In 5 of the anephric patients, an increased plasma aldosterone concentration (PAC) in response to ACTH stimulation had previously been demonstrated. After A-II stimulation, all 8 anephric patients responded with a significant rise in PAC although the increase was less pronounced than in 4 non-nephrectomized patients. In both groups of patients the increase in PAC was correlated to the increase in diastolic and systolic BP and to the A-II dose. Furthermore, in the non-nephrectomized patients, the plasma renin activity showed a significant decline, which was inversely correlated to the increase in PAC. When all 12 patients, regardless of the difference in remaining renin-angiotensin system, were considered as one population, the variable basal levels of PAC correlated significantly to the increase in PAC during A-II and ACTH stimulation. It is concluded that the adrenals of anephric man respond to A-II with an increase in PAC and that the reason for a lower response appears to be the lack of the renin-angiotensin system.", "contents": "The adrenocortical response to angiotensin II infusion in anephric and non-nephrectomized patients on regular hemodialysis. In the present study 8 anephric and 4 non-nephrectomized patients were stimulated with angiotensin II (A-II). In 5 of the anephric patients, an increased plasma aldosterone concentration (PAC) in response to ACTH stimulation had previously been demonstrated. After A-II stimulation, all 8 anephric patients responded with a significant rise in PAC although the increase was less pronounced than in 4 non-nephrectomized patients. In both groups of patients the increase in PAC was correlated to the increase in diastolic and systolic BP and to the A-II dose. Furthermore, in the non-nephrectomized patients, the plasma renin activity showed a significant decline, which was inversely correlated to the increase in PAC. When all 12 patients, regardless of the difference in remaining renin-angiotensin system, were considered as one population, the variable basal levels of PAC correlated significantly to the increase in PAC during A-II and ACTH stimulation. It is concluded that the adrenals of anephric man respond to A-II with an increase in PAC and that the reason for a lower response appears to be the lack of the renin-angiotensin system."}
{"id": "PMID:199050", "title": "On the functional significance of sleep.", "content": "Some aspects of the functional significance of sleep are considered. These involve studies on (i) the dynamics of electrical activity in the neo- and archi-paleocortical structures of the brain in the sleep-wakefulness cycle, (ii) the effect of selective deprivation of different sleep phases on the sleep-wakefulness cycle, (iii) effect of stimulating synchronizing and desynchronizing systems on the sleep-wakefulness cycle, and (iv) the dynamics of emotional tension in the sleep-wakefulness cycle. Analysis of our findings and their comparison with those reported in the literature support a hypothesis that every phase in the sleep-wakefulness cycle operates in two directions; it withdraws the factors formed in the previous phase which are potentially aimed at disturbing brain homeostasis; and, at the same time, it forms new antihomeostatic factors, withdrawal of which requires the triggering and work of a subsequent phase. The triggering links of the systems regulating each phase are very sensitive to the factors formed in the preceding phase. Therefore, in normal conditions the anti-homeostatic factors fail to attain a critical level of disturbance of homeostasis of the brain, since the threshold for their activation is far lower than the critical level of homeostatic disturbance. Activation of the triggering links of the paradoxical phase and wakefulness seems to be mediated through the same anti-homeostatic factors formed in the orthodox phase. However, the threshold for activation of the paradoxical phase is lower than that of wakefulness. As a consequence, the orthodox phase readily passes into the paradoxical. The latter, effectively reducing the antihomeostatic factors formed in the orthodox phase, prevents the onset of undue awakening that would have been undesirable because there would have been insufficient time for inactivation of the anti-homeostatic factors formed during wakefulness.", "contents": "On the functional significance of sleep. Some aspects of the functional significance of sleep are considered. These involve studies on (i) the dynamics of electrical activity in the neo- and archi-paleocortical structures of the brain in the sleep-wakefulness cycle, (ii) the effect of selective deprivation of different sleep phases on the sleep-wakefulness cycle, (iii) effect of stimulating synchronizing and desynchronizing systems on the sleep-wakefulness cycle, and (iv) the dynamics of emotional tension in the sleep-wakefulness cycle. Analysis of our findings and their comparison with those reported in the literature support a hypothesis that every phase in the sleep-wakefulness cycle operates in two directions; it withdraws the factors formed in the previous phase which are potentially aimed at disturbing brain homeostasis; and, at the same time, it forms new antihomeostatic factors, withdrawal of which requires the triggering and work of a subsequent phase. The triggering links of the systems regulating each phase are very sensitive to the factors formed in the preceding phase. Therefore, in normal conditions the anti-homeostatic factors fail to attain a critical level of disturbance of homeostasis of the brain, since the threshold for their activation is far lower than the critical level of homeostatic disturbance. Activation of the triggering links of the paradoxical phase and wakefulness seems to be mediated through the same anti-homeostatic factors formed in the orthodox phase. However, the threshold for activation of the paradoxical phase is lower than that of wakefulness. As a consequence, the orthodox phase readily passes into the paradoxical. The latter, effectively reducing the antihomeostatic factors formed in the orthodox phase, prevents the onset of undue awakening that would have been undesirable because there would have been insufficient time for inactivation of the anti-homeostatic factors formed during wakefulness."}
{"id": "PMID:199051", "title": "Supratentorial recurrences of gliomas. Morphological studies in relation to time intervals with oligodendrogliomas.", "content": "On the basis of a three stage grading system we report 23 stage one recurrent oligodendrogliomas (O 1), and 29 stage two recurrent oligodendrogliomas (O 2). In the O 1 group after the first interval 15 became O 2 and 2 became glioblastomas. Twenty tumours of the O 2 group after the first interval were not changed, three became oligodendroglioma-astrocytomas stage 2, and six became glioblastomas. The time relation for the recurrent phase in the primary O 1 group is calculated as 42 months, and in the primary O 2 group as 22 months, but this is without significance. For the development of malignancy, especially for the change to glioblastoma, a prominent participation by transformed local astrocytes seems to be essential. Postoperative irradiation most probably does not favour malignant change. A prolongation of the expectation of life by radiotherapy is not noticed.", "contents": "Supratentorial recurrences of gliomas. Morphological studies in relation to time intervals with oligodendrogliomas. On the basis of a three stage grading system we report 23 stage one recurrent oligodendrogliomas (O 1), and 29 stage two recurrent oligodendrogliomas (O 2). In the O 1 group after the first interval 15 became O 2 and 2 became glioblastomas. Twenty tumours of the O 2 group after the first interval were not changed, three became oligodendroglioma-astrocytomas stage 2, and six became glioblastomas. The time relation for the recurrent phase in the primary O 1 group is calculated as 42 months, and in the primary O 2 group as 22 months, but this is without significance. For the development of malignancy, especially for the change to glioblastoma, a prominent participation by transformed local astrocytes seems to be essential. Postoperative irradiation most probably does not favour malignant change. A prolongation of the expectation of life by radiotherapy is not noticed."}
{"id": "PMID:199052", "title": "Lymphocytic infiltration in long-survival glioblastomas: possible host's resistance.", "content": "A series of 200 patients operated on at the Rome University Neurosurgical Clinic for primary glioblastoma is analyzed. Eight of these patients (4%) survived for over four years. The histological preparations showed more or less heavy perivascular lymphocytic infiltration in six of these cases. Since such infiltrations in malignant tumours of other organs are recognized as having an immune function, expressing the host's resistance to his tumour, the longer survival of the cases considered may well denote an immune defensive mechanism.", "contents": "Lymphocytic infiltration in long-survival glioblastomas: possible host's resistance. A series of 200 patients operated on at the Rome University Neurosurgical Clinic for primary glioblastoma is analyzed. Eight of these patients (4%) survived for over four years. The histological preparations showed more or less heavy perivascular lymphocytic infiltration in six of these cases. Since such infiltrations in malignant tumours of other organs are recognized as having an immune function, expressing the host's resistance to his tumour, the longer survival of the cases considered may well denote an immune defensive mechanism."}
{"id": "PMID:199056", "title": "Multiple hepatic tumors and peliosis hepatis in Fanconi's anemia treated with androgens.", "content": "We report the case of a 13-year-old boy who was known to have Fanconi's anemia for five years. For treatment of this condition he was given androgens and corticosteroids. Two months before his death, severe varicella developed complicated by pneumonia, jaundice, and prolonged fever; all of which resolved during a five-week hospitalization. Three weeks later he died of Clostridium septicum sepsis caused by necrotizing enterocolitis. At autopsy he was found to have multiple hepatocellular neoplasms. A striking feature of the neoplasms was cholestasis. The liver also showed peliosis hepatis. The association of the use of certain androgenic steroids with hepatic neoplasms histologically resembling hepatocarcinomas, but characterized by lack of metastases and apparent reversibility, suggests the desirability of a new nomenclature for these hepatocellular lesions.", "contents": "Multiple hepatic tumors and peliosis hepatis in Fanconi's anemia treated with androgens. We report the case of a 13-year-old boy who was known to have Fanconi's anemia for five years. For treatment of this condition he was given androgens and corticosteroids. Two months before his death, severe varicella developed complicated by pneumonia, jaundice, and prolonged fever; all of which resolved during a five-week hospitalization. Three weeks later he died of Clostridium septicum sepsis caused by necrotizing enterocolitis. At autopsy he was found to have multiple hepatocellular neoplasms. A striking feature of the neoplasms was cholestasis. The liver also showed peliosis hepatis. The association of the use of certain androgenic steroids with hepatic neoplasms histologically resembling hepatocarcinomas, but characterized by lack of metastases and apparent reversibility, suggests the desirability of a new nomenclature for these hepatocellular lesions."}
{"id": "PMID:199057", "title": "Granular cell myoblastoma of the gallbladder.", "content": "A case of granular cell myoblastoma of the gallbladder in a 39-year old Japanese female is presented. Granular cell myoblastomas arising in the biliary tract are a rare occurrence. This tumor has not yet been reported in the gallbladder.", "contents": "Granular cell myoblastoma of the gallbladder. A case of granular cell myoblastoma of the gallbladder in a 39-year old Japanese female is presented. Granular cell myoblastomas arising in the biliary tract are a rare occurrence. This tumor has not yet been reported in the gallbladder."}
{"id": "PMID:199058", "title": "Amebic granuloma--an experimental study.", "content": "The etiopathogenesis of granuloma formation in amebiasis is not known. An experimental study was carried out in 48 guinea pigs arranged into four groups, to assess the role of hypersensitivity in formation of amebic granuloma. Repeated intracecal inoculations of saline in Group I and mixed amebic and bacterial suspension in other groups were made. Animals in Group III were sensitized by amebic antigen and in Group IV by bacterial antigen before inoculations. Lesions produced in the amebic hypersensitive group of animals were notably different from those in other groups. A higher frequency of cecal ulceration and a significantly severe grade of cecal damage was seen in these animals. Extensive pericecal adhesions and marked thickening of the wall produced nodular lesions. Granulomas were formed with dense chronic inflammatory cell infiltration including fibroblasts.", "contents": "Amebic granuloma--an experimental study. The etiopathogenesis of granuloma formation in amebiasis is not known. An experimental study was carried out in 48 guinea pigs arranged into four groups, to assess the role of hypersensitivity in formation of amebic granuloma. Repeated intracecal inoculations of saline in Group I and mixed amebic and bacterial suspension in other groups were made. Animals in Group III were sensitized by amebic antigen and in Group IV by bacterial antigen before inoculations. Lesions produced in the amebic hypersensitive group of animals were notably different from those in other groups. A higher frequency of cecal ulceration and a significantly severe grade of cecal damage was seen in these animals. Extensive pericecal adhesions and marked thickening of the wall produced nodular lesions. Granulomas were formed with dense chronic inflammatory cell infiltration including fibroblasts."}
{"id": "PMID:199059", "title": "Antibodies to Epstein-Barr virus capsid antigen and early antigen in nasopharyngeal carcinoma and comparison groups.", "content": "Antibodies to Epstein-Barr virus capsid antigen (anti-VCA) and early antigen (anti-EA) were measured in 263 patients with nasopharyngeal carcinoma (NPC), 624 age- and sex-matched neighborhood controls, 570 family members of NPC patients and 830 family members of neighborhood controls in Taiwan. The distribution of antibody titers was significantly different between NPC patients and the other three groups. More than 55% and 45% of NPC patients had titers of greater than or equal to 1:640 and greater than or equal to 1:80 for anti-VCA and anti-EA, respectively, while less than 6.7% and 2.5% of the other three groups had such high titers. The geometric means of anti-VCA and anti-EA titers were 1:352 and 1:45, respectively, in NPC patients compared to less than 1:77 and 1:12, respectively, in the comparison groups. Anti-VCA and anti-EA titers were significantly correlated. The association of EBV with NPC is discussed.", "contents": "Antibodies to Epstein-Barr virus capsid antigen and early antigen in nasopharyngeal carcinoma and comparison groups. Antibodies to Epstein-Barr virus capsid antigen (anti-VCA) and early antigen (anti-EA) were measured in 263 patients with nasopharyngeal carcinoma (NPC), 624 age- and sex-matched neighborhood controls, 570 family members of NPC patients and 830 family members of neighborhood controls in Taiwan. The distribution of antibody titers was significantly different between NPC patients and the other three groups. More than 55% and 45% of NPC patients had titers of greater than or equal to 1:640 and greater than or equal to 1:80 for anti-VCA and anti-EA, respectively, while less than 6.7% and 2.5% of the other three groups had such high titers. The geometric means of anti-VCA and anti-EA titers were 1:352 and 1:45, respectively, in NPC patients compared to less than 1:77 and 1:12, respectively, in the comparison groups. Anti-VCA and anti-EA titers were significantly correlated. The association of EBV with NPC is discussed."}
{"id": "PMID:199060", "title": "Atypical herpesvirus hominis type 2 infection in uremic patients receiving immunosuppressive therapy.", "content": "In four uremic patients (three renal transplant recipients and one with idiopathic thrombocytopenia), painful, initially vesicular lesions developed in the anogenital region while they were receiving immunosuppressive drug therapy. These lesions enlarged, coalesced and ulcerated, presenting a puzzling diagnostic problem. Initial misdiagnoses often resulted in inappropriate antimicrobial therapy. Routine cultures, histologic sections and Tzanck preparations were seldom helpful. The correct diagnosis of herpesvirus hominis (HVH) infection was established within 18 to 48 hours by viral culture of swab or biopsy material. Subsequent identification of isolates as HVH type 2 was confirmed by neutralization kinetics, infectivity titers and ability to plaque in chick embryo cells. Various therapeutic regimens were ineffective. Clinical improvement best correlated with decrease in dosage of immunosuppressive agents.", "contents": "Atypical herpesvirus hominis type 2 infection in uremic patients receiving immunosuppressive therapy. In four uremic patients (three renal transplant recipients and one with idiopathic thrombocytopenia), painful, initially vesicular lesions developed in the anogenital region while they were receiving immunosuppressive drug therapy. These lesions enlarged, coalesced and ulcerated, presenting a puzzling diagnostic problem. Initial misdiagnoses often resulted in inappropriate antimicrobial therapy. Routine cultures, histologic sections and Tzanck preparations were seldom helpful. The correct diagnosis of herpesvirus hominis (HVH) infection was established within 18 to 48 hours by viral culture of swab or biopsy material. Subsequent identification of isolates as HVH type 2 was confirmed by neutralization kinetics, infectivity titers and ability to plaque in chick embryo cells. Various therapeutic regimens were ineffective. Clinical improvement best correlated with decrease in dosage of immunosuppressive agents."}
{"id": "PMID:199061", "title": "Cytomegalovirus retinitis in adults. A manifestation of disseminated viral infection.", "content": "Retinitis caused by cytomegalovirus (CMV) infection is unusual in adults. Sixteen of the 17 cases reported have occurred in immunologically compromised patients, most frequently renal transplant recipients. CMV retinitis is associated with a distinctive ophthalmoscopic appearance and, in the majority of cases, was the first clinical manifestation of systemic viral infection. Severe and permanent visual deficits are characteristic. Since retinitis is a reliable sign of disseminated disease and ophthalmoscopic examination a rapid method of establishing its presence, recognition of this manifestation should allow earlier diagnosis of serious CMV infection.", "contents": "Cytomegalovirus retinitis in adults. A manifestation of disseminated viral infection. Retinitis caused by cytomegalovirus (CMV) infection is unusual in adults. Sixteen of the 17 cases reported have occurred in immunologically compromised patients, most frequently renal transplant recipients. CMV retinitis is associated with a distinctive ophthalmoscopic appearance and, in the majority of cases, was the first clinical manifestation of systemic viral infection. Severe and permanent visual deficits are characteristic. Since retinitis is a reliable sign of disseminated disease and ophthalmoscopic examination a rapid method of establishing its presence, recognition of this manifestation should allow earlier diagnosis of serious CMV infection."}
{"id": "PMID:199063", "title": "The natural history of hypertrophic gastrophy (Menetrier's disease). Report of a case with 16 year follow-up and review of 120 cases from the literature.", "content": "We describe a 33 year old man who presented with epigastric pain, weight loss and hematemesis. Roentgenograms of the upper gastrointestinal tract and endoscopy demonstrated giant rugal folds, and the diagnosis of hypertrophic gastropathy was confirmed by operative biopsy. This patient's symptoms and abnormalities noted on the roentgenograms persisted until his death 16 years later. Postmortem examination confirmed the persistence of hypertrophic gastropathy and revealed, in addition, a hepatocellular carcinoma metastatic to the stomach and regional lymph nodes. A review of 120 previously reported cases of hypertrophic gastropathy with special attention to its natural history indicates that the chronic nature of this patient's illness is typical. In addition, the chance of gastric carcinoma developing in these patients is appreciable. Since the reported long-term results of operative therapy appear favorable, patients with persistent and sufficiently distressing symptoms should be considered for gastric resection.", "contents": "The natural history of hypertrophic gastrophy (Menetrier's disease). Report of a case with 16 year follow-up and review of 120 cases from the literature. We describe a 33 year old man who presented with epigastric pain, weight loss and hematemesis. Roentgenograms of the upper gastrointestinal tract and endoscopy demonstrated giant rugal folds, and the diagnosis of hypertrophic gastropathy was confirmed by operative biopsy. This patient's symptoms and abnormalities noted on the roentgenograms persisted until his death 16 years later. Postmortem examination confirmed the persistence of hypertrophic gastropathy and revealed, in addition, a hepatocellular carcinoma metastatic to the stomach and regional lymph nodes. A review of 120 previously reported cases of hypertrophic gastropathy with special attention to its natural history indicates that the chronic nature of this patient's illness is typical. In addition, the chance of gastric carcinoma developing in these patients is appreciable. Since the reported long-term results of operative therapy appear favorable, patients with persistent and sufficiently distressing symptoms should be considered for gastric resection."}
{"id": "PMID:199064", "title": "An epidemiologic study of cancer of the cervix, vagina, and vulva based on the Third National Cancer Survey in the United States.", "content": "Cases of invasive and in situ carcinoma of the lower female genital tract as reported in the Third National Cancer Survey in the United States were analyzed according to age, race, and geographic distribution. Results indicate that the incidence rates of in situ and invasive carcinoma of the cervix were greater in black than in white women, with a relative risk rate for black women of approximately two for both types of cervical carcinoma. For white women, the age-specific rates for invasive carcinoma of the cervix remained relatively constant after age 45, while for black women the age-specific rates for invasive carcinoma continued to increase after age 45. For both races, the patterns of age-specific incidence rates for in situ and invasive carcinoma of the cervix were not similar to those for carcinoma of the vagina or vulva. The pattern of age-specific incidence rates of adenocarcinoma of the cervix did not resemble those for in situ or invasive squamous cell carcinoma of the cervix. The rates for adenocarcinoma of the cervix demonstrated patterns similar to those for intraductal carcinoma of the breast. Results of the study are discussed in relationship to the field theory of carcinogenesis as developed for the lower female genital tract.", "contents": "An epidemiologic study of cancer of the cervix, vagina, and vulva based on the Third National Cancer Survey in the United States. Cases of invasive and in situ carcinoma of the lower female genital tract as reported in the Third National Cancer Survey in the United States were analyzed according to age, race, and geographic distribution. Results indicate that the incidence rates of in situ and invasive carcinoma of the cervix were greater in black than in white women, with a relative risk rate for black women of approximately two for both types of cervical carcinoma. For white women, the age-specific rates for invasive carcinoma of the cervix remained relatively constant after age 45, while for black women the age-specific rates for invasive carcinoma continued to increase after age 45. For both races, the patterns of age-specific incidence rates for in situ and invasive carcinoma of the cervix were not similar to those for carcinoma of the vagina or vulva. The pattern of age-specific incidence rates of adenocarcinoma of the cervix did not resemble those for in situ or invasive squamous cell carcinoma of the cervix. The rates for adenocarcinoma of the cervix demonstrated patterns similar to those for intraductal carcinoma of the breast. Results of the study are discussed in relationship to the field theory of carcinogenesis as developed for the lower female genital tract."}
{"id": "PMID:199065", "title": "Cytomegalovirus retinitis secondary to chronic viremia in phagocytic leukocytes.", "content": "We studied the relationship between the duration and intensity of cytomegalovirus viremia, cytomegalovirus complement fixing antibody, and cytomegalovirus retinitis in 61 renal transplant recipients. Five (8%) patients had chronic viremia which lasted more than six months. Two of the five developed typical cytomegalovirus retinitis and a severe fungal infection after intensive viremia of more than 11 months' duration. Retinitis did not develop in 22 patients with short-term viremia. Infectious cytomegalovirus was largely associated with polymorphonuclear leukocytes, but the virus was associated with monocytes during the immature granulocytic response accompanying one patient's terminal illness.", "contents": "Cytomegalovirus retinitis secondary to chronic viremia in phagocytic leukocytes. We studied the relationship between the duration and intensity of cytomegalovirus viremia, cytomegalovirus complement fixing antibody, and cytomegalovirus retinitis in 61 renal transplant recipients. Five (8%) patients had chronic viremia which lasted more than six months. Two of the five developed typical cytomegalovirus retinitis and a severe fungal infection after intensive viremia of more than 11 months' duration. Retinitis did not develop in 22 patients with short-term viremia. Infectious cytomegalovirus was largely associated with polymorphonuclear leukocytes, but the virus was associated with monocytes during the immature granulocytic response accompanying one patient's terminal illness."}
{"id": "PMID:199066", "title": "Effect of polychlorinated biphenyl (PCB) on the thyroid gland of rats. Ultrastructural and biochemical investigations.", "content": "Polychlorinated biphenyls (PCB) produced ultrastructural lesions in thyroid follicular cells and reductions in serum thyroxine levels in rats that were time- and dose-dependent. The acute effects (4 week) of PCB (50 and 500 ppm) consisted of an accumulation of lysosomal bodies and colloid droplets in follicular cells with abnormalities of microvilli on the luminal surface. The chronic administration (12 week) of PCB (50 and 500/250 ppm) resulted in a striking distention of many follicular cells with large lysosomal bodies with strong acid phosphatase activity and colloid droplets, blunt and abnormally branched microvilli, and mitochondrial vacuolation. These ultrastructural alterations in follicular cells were associated with a highly significant reduction in serum thyroxine with both the low and the high dose of PCB. Follicular cells remained responsive to the lowered thyroxine level after feeding PCB for 4 and 12 weeks 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 colloid. Residual ultrastructural alterations persisted for 12 weeks following cessation of feeding the compound, and serum thyroxine levels were significantly lower than in control rats. However, 35 weeks after discontinuing PCB, thyroid follicular cells were similar to those in controls and serum thyroxine levels had returned to normal. The striking ultrastructural lesions in follicular cells produced by feeding PCB to rats appeared to contribute to the lowering of serum thyroxine levels, in combination with the known stimulation of peripheral thyroxine metabolism by these compounds. Certain metabolic alterations produced by PCB intoxication in experimental animals and human beings may be related to an alteration in thyroid function.", "contents": "Effect of polychlorinated biphenyl (PCB) on the thyroid gland of rats. Ultrastructural and biochemical investigations. Polychlorinated biphenyls (PCB) produced ultrastructural lesions in thyroid follicular cells and reductions in serum thyroxine levels in rats that were time- and dose-dependent. The acute effects (4 week) of PCB (50 and 500 ppm) consisted of an accumulation of lysosomal bodies and colloid droplets in follicular cells with abnormalities of microvilli on the luminal surface. The chronic administration (12 week) of PCB (50 and 500/250 ppm) resulted in a striking distention of many follicular cells with large lysosomal bodies with strong acid phosphatase activity and colloid droplets, blunt and abnormally branched microvilli, and mitochondrial vacuolation. These ultrastructural alterations in follicular cells were associated with a highly significant reduction in serum thyroxine with both the low and the high dose of PCB. Follicular cells remained responsive to the lowered thyroxine level after feeding PCB for 4 and 12 weeks 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 colloid. Residual ultrastructural alterations persisted for 12 weeks following cessation of feeding the compound, and serum thyroxine levels were significantly lower than in control rats. However, 35 weeks after discontinuing PCB, thyroid follicular cells were similar to those in controls and serum thyroxine levels had returned to normal. The striking ultrastructural lesions in follicular cells produced by feeding PCB to rats appeared to contribute to the lowering of serum thyroxine levels, in combination with the known stimulation of peripheral thyroxine metabolism by these compounds. Certain metabolic alterations produced by PCB intoxication in experimental animals and human beings may be related to an alteration in thyroid function."}
{"id": "PMID:199068", "title": "Role of cyclic 3',5'-GMP in modulation of cellular uptake of phosphate.", "content": "The role of cGMP in regulating renal cortical phosphate uptake was investigated in rats. Cyclic GMP (1 mM) produced a 27.7% +/- 1.4 (SE) increase in 32PO4 uptake by isolated renal cortical tubules (P less than 0.001) and cAMP (1 mM) a 28.7% +/- 1.4 increase (P less than 0.001), but their effects were not additive. Acetylcholine (Ach) (1 mM), in the presence of theophylline (T) (10 mM), increased cGMP in cortical slices from 24.1 pmol/g wet wt +/- 1.3 to 76.5 +/- 5.2 (P less than 0.001), but had no effect on cAMP, and Ach (1 mM) in the presence of T (1 mM) increased 32PO4 uptake 19.1% +/- 1.1 (P less than 0.001). Addition of Ca2+ to the incubation medium in the presence of T (10 mM) significantly increased cGMP in cortical slices from 7.4 pmol/g wet wt +/- 0.6 (0 Ca2+ plus EGTA, 0.5 mM) to 24.1 +/- 1.3 (1 mM Ca2+) and caused a 52.2% +/- 2.7 rise in 32PO4 uptake (P less than 0.001). Cyclic AMP was decreased by the addition of Ca2+. In summary, cGMP and cAMP stimulate 32PO4 uptake by renal cortex, and Ach and Ca2+ increase both cGMP and 32PO4 but do not increase cAMP. These data suggest that cGMP may play a role in regulating cellular uptake of phosphate.", "contents": "Role of cyclic 3',5'-GMP in modulation of cellular uptake of phosphate. The role of cGMP in regulating renal cortical phosphate uptake was investigated in rats. Cyclic GMP (1 mM) produced a 27.7% +/- 1.4 (SE) increase in 32PO4 uptake by isolated renal cortical tubules (P less than 0.001) and cAMP (1 mM) a 28.7% +/- 1.4 increase (P less than 0.001), but their effects were not additive. Acetylcholine (Ach) (1 mM), in the presence of theophylline (T) (10 mM), increased cGMP in cortical slices from 24.1 pmol/g wet wt +/- 1.3 to 76.5 +/- 5.2 (P less than 0.001), but had no effect on cAMP, and Ach (1 mM) in the presence of T (1 mM) increased 32PO4 uptake 19.1% +/- 1.1 (P less than 0.001). Addition of Ca2+ to the incubation medium in the presence of T (10 mM) significantly increased cGMP in cortical slices from 7.4 pmol/g wet wt +/- 0.6 (0 Ca2+ plus EGTA, 0.5 mM) to 24.1 +/- 1.3 (1 mM Ca2+) and caused a 52.2% +/- 2.7 rise in 32PO4 uptake (P less than 0.001). Cyclic AMP was decreased by the addition of Ca2+. In summary, cGMP and cAMP stimulate 32PO4 uptake by renal cortex, and Ach and Ca2+ increase both cGMP and 32PO4 but do not increase cAMP. These data suggest that cGMP may play a role in regulating cellular uptake of phosphate."}
{"id": "PMID:199069", "title": "Development-dependent responses of ovarian follicles to FSH and hCG.", "content": "Ovarian follicles removed from immature rats (preantral follicles) and immature rats treated in vivo with follicle stimulating hormone (FSH) (antral follicles) released progesterone in vitro in response to either human chorionic gonadotropin (hCG), hFSH, or DBcAMP in a time- and concentration-dependent fashion. Antral follicles produced approximately 20 times more progesterone than preantral follicles in response to both FSH and hCG at 10(-7) M and approximately 5 times more progesterone in  response to 8 X 10(-3) M DBcAMP. After in vitro incubations, follicles were transplanted beneath the kidney capsules of recipient rats to assess their ability to luteinize after hormonal stimulation. Only antral follicles incubated with hCG, hFSH, and DBcAMP formed ectopic corpora lutea. Adenylate cyclase activity in preantral and antral follicle granulosa cells increased in response to both 10 mM KF and 10(-6) M hFSH with no major differences observed between membranes prepared from preantral or antral follicle granulosa cells. These results demonstrate that follicular maturation is associated with major changes in the ability of the granulosa cells to produce progesterone and luteinize in response to hormonal stimulation and that these changes may be, in part, independent of a functional hormone-responsive adenylate cyclase system.", "contents": "Development-dependent responses of ovarian follicles to FSH and hCG. Ovarian follicles removed from immature rats (preantral follicles) and immature rats treated in vivo with follicle stimulating hormone (FSH) (antral follicles) released progesterone in vitro in response to either human chorionic gonadotropin (hCG), hFSH, or DBcAMP in a time- and concentration-dependent fashion. Antral follicles produced approximately 20 times more progesterone than preantral follicles in response to both FSH and hCG at 10(-7) M and approximately 5 times more progesterone in  response to 8 X 10(-3) M DBcAMP. After in vitro incubations, follicles were transplanted beneath the kidney capsules of recipient rats to assess their ability to luteinize after hormonal stimulation. Only antral follicles incubated with hCG, hFSH, and DBcAMP formed ectopic corpora lutea. Adenylate cyclase activity in preantral and antral follicle granulosa cells increased in response to both 10 mM KF and 10(-6) M hFSH with no major differences observed between membranes prepared from preantral or antral follicle granulosa cells. These results demonstrate that follicular maturation is associated with major changes in the ability of the granulosa cells to produce progesterone and luteinize in response to hormonal stimulation and that these changes may be, in part, independent of a functional hormone-responsive adenylate cyclase system."}
{"id": "PMID:199070", "title": "Effect of leukocytic endogenous mediators on endocrine pancreas secretory responses.", "content": "Crude mediators from stimulated rabbit peritoneal leukocytes (LEM) engender numerous physiologic alterations in rats, which are similar to those observed during infection. One hour after the intraperitoneal injection of crude LEM, plasma insulin and glucagon concentrations are elevated; at 2 h the hormonal alterations are manifested by a 30% increase in hepatic cyclic adenosine 3',5'-monophosphate (cAMP), glycogen depression, and uptake of 14C-labeled nonmetabolizable amino acid analogues (AA). Plasma hormone concentrations reach maximum levels by 5 h and decline by 24 h. The hepatic concentrations of AA parallel the insulin and glucagon responses and correlate with the inverse of insulin/glucagon molar ratio. In spite of mobilization of hepatic glycogen evident at 5 h, plasma glucose concentrations were transiently depressed. Plasma insulin, glucagon, and hepatic AA concentrations were dose dependent. Plasma insulin and glucagon responses to crude LEM may explain increases in hepatic cAMP, uptake of AA, and glycogenolysis as well as hypoglycemia. These data partially characterize the role of crude LEM, provide an explanation for the stimuli-inducing hyperglucagonemia and hyperinsulinemia during infection. They implicate the endocrine pancreas as a factor regulating the host's metabolic response to infection.", "contents": "Effect of leukocytic endogenous mediators on endocrine pancreas secretory responses. Crude mediators from stimulated rabbit peritoneal leukocytes (LEM) engender numerous physiologic alterations in rats, which are similar to those observed during infection. One hour after the intraperitoneal injection of crude LEM, plasma insulin and glucagon concentrations are elevated; at 2 h the hormonal alterations are manifested by a 30% increase in hepatic cyclic adenosine 3',5'-monophosphate (cAMP), glycogen depression, and uptake of 14C-labeled nonmetabolizable amino acid analogues (AA). Plasma hormone concentrations reach maximum levels by 5 h and decline by 24 h. The hepatic concentrations of AA parallel the insulin and glucagon responses and correlate with the inverse of insulin/glucagon molar ratio. In spite of mobilization of hepatic glycogen evident at 5 h, plasma glucose concentrations were transiently depressed. Plasma insulin, glucagon, and hepatic AA concentrations were dose dependent. Plasma insulin and glucagon responses to crude LEM may explain increases in hepatic cAMP, uptake of AA, and glycogenolysis as well as hypoglycemia. These data partially characterize the role of crude LEM, provide an explanation for the stimuli-inducing hyperglucagonemia and hyperinsulinemia during infection. They implicate the endocrine pancreas as a factor regulating the host's metabolic response to infection."}
{"id": "PMID:199072", "title": "Neurons in medullary areas controlling ACTH: atrial input and rostral projections.", "content": "To examine hindbrain pathways mediating release of adrenocorticotropin (ACTH) in response to hemodynamic changes we tested, in 19 cats (chloralose/urethan), 70 neurons in ACTH-active areas of the medulla for their response to volume pulsation (+/- 1 ml, 1 Hz, 60 s) of the right atrium (RA) or to hemorrhage (3 ml/kg per 30 s), and to electrical stimulation in ACTH-active areas of the dorsal rostral pons (DRP). The activity of 16 neurons was increased (P less than 0.05) by RA. Of these, 6 were driven antidromically from the locus subcoeruleus (LSC), and were located in the lateral solitary nucleus and in posteromedial nucleus intercalatus (NI). The activity of 11 neurons was decreased by RA. Of these, 5 were driven antidromically from LSC and lateral ventral tegmental nucleus and were located in anterolateral NI. No rostral projections were found to more medial sites in DRP. Responses to the first trial of RA were rapid, but slowed and attenuated with repeated trials. Responses to hemorrhage were rapid and in the opposite direction, but did not attenuate. The results suggest that pathways displaying rate sensitivity project from the right atrium via B-receptors to the DRP.", "contents": "Neurons in medullary areas controlling ACTH: atrial input and rostral projections. To examine hindbrain pathways mediating release of adrenocorticotropin (ACTH) in response to hemodynamic changes we tested, in 19 cats (chloralose/urethan), 70 neurons in ACTH-active areas of the medulla for their response to volume pulsation (+/- 1 ml, 1 Hz, 60 s) of the right atrium (RA) or to hemorrhage (3 ml/kg per 30 s), and to electrical stimulation in ACTH-active areas of the dorsal rostral pons (DRP). The activity of 16 neurons was increased (P less than 0.05) by RA. Of these, 6 were driven antidromically from the locus subcoeruleus (LSC), and were located in the lateral solitary nucleus and in posteromedial nucleus intercalatus (NI). The activity of 11 neurons was decreased by RA. Of these, 5 were driven antidromically from LSC and lateral ventral tegmental nucleus and were located in anterolateral NI. No rostral projections were found to more medial sites in DRP. Responses to the first trial of RA were rapid, but slowed and attenuated with repeated trials. Responses to hemorrhage were rapid and in the opposite direction, but did not attenuate. The results suggest that pathways displaying rate sensitivity project from the right atrium via B-receptors to the DRP."}
{"id": "PMID:199074", "title": "Structure-function relationships of peptide fragments of gastrin and cholecystokinin.", "content": "This study evaluates the structure-function relationships of the C-terminal peptide fragments of gastrin and cholecystokinin (CCK) in the biliary system and the stomach. Dogs with chronic biliary and gastric fistulas were used. Administration of the common fragments of CCK and gastrin with four and five amino acids and the active fragments of CCK with six through eight amino acids without sulfation of tyrosine in position 7 failed to alter hepatic bile flow from control values while significantly stimulating gastric hydrogen ion output. Administration of the seven and eight amino acid peptide fragments of CCK with sulfation of tyrosine in position 7 significantly increased hepatic bile flow. Administration of the sulfated octapeptide with 4 microgram/kg per h of nonsulfated octapeptide did not result in the inhibition of the choleresis produced by the sulfated peptide. The gastric hydrogen ion response produced by the administration of the nonsulfated and sulfated peptide was equal to that of the nonsulfated peptide alone. These results suggest that in the biliary system the receptor is highly specific as sulfation of the peptide fragment of CCK is essential for combining with the receptor, whereas in the stomach the receptor has little specificity and combines with all of the peptide fragments evaluated.", "contents": "Structure-function relationships of peptide fragments of gastrin and cholecystokinin. This study evaluates the structure-function relationships of the C-terminal peptide fragments of gastrin and cholecystokinin (CCK) in the biliary system and the stomach. Dogs with chronic biliary and gastric fistulas were used. Administration of the common fragments of CCK and gastrin with four and five amino acids and the active fragments of CCK with six through eight amino acids without sulfation of tyrosine in position 7 failed to alter hepatic bile flow from control values while significantly stimulating gastric hydrogen ion output. Administration of the seven and eight amino acid peptide fragments of CCK with sulfation of tyrosine in position 7 significantly increased hepatic bile flow. Administration of the sulfated octapeptide with 4 microgram/kg per h of nonsulfated octapeptide did not result in the inhibition of the choleresis produced by the sulfated peptide. The gastric hydrogen ion response produced by the administration of the nonsulfated and sulfated peptide was equal to that of the nonsulfated peptide alone. These results suggest that in the biliary system the receptor is highly specific as sulfation of the peptide fragment of CCK is essential for combining with the receptor, whereas in the stomach the receptor has little specificity and combines with all of the peptide fragments evaluated."}
{"id": "PMID:199075", "title": "Barrier and uptake mechanisms in the cerebrovascular response to noradrenaline.", "content": "Cerebral blood flow (CBF) was measured in 20 baboons by the intra-arterial xenon-133 injection method. The CBF responses to intra-arterial infusions of noradrenaline (NA) were determined. These responses were normally found to be vasodilator and mediated by beta adrenoreceptors. After infusion of substances blocking extraneuronal uptake of NA or opening of the blood-brain barrier, this vasodilation was either abolished or converted to an alpha-receptor mediated vasoconstriction. This suggests that normally the cerebral circulation is protected against noradrenergic vasoconstriction by mechanisms reducing the concentration of NA in the tunica media to below threshold for alpha-adrenoreceptor stimulation.", "contents": "Barrier and uptake mechanisms in the cerebrovascular response to noradrenaline. Cerebral blood flow (CBF) was measured in 20 baboons by the intra-arterial xenon-133 injection method. The CBF responses to intra-arterial infusions of noradrenaline (NA) were determined. These responses were normally found to be vasodilator and mediated by beta adrenoreceptors. After infusion of substances blocking extraneuronal uptake of NA or opening of the blood-brain barrier, this vasodilation was either abolished or converted to an alpha-receptor mediated vasoconstriction. This suggests that normally the cerebral circulation is protected against noradrenergic vasoconstriction by mechanisms reducing the concentration of NA in the tunica media to below threshold for alpha-adrenoreceptor stimulation."}
{"id": "PMID:199076", "title": "Malignant salivary gland neoplasms of the lip.", "content": "The charts of fourteen patients with malignant salivary gland tumors of the lip were reviewed. These patients represented 1 per cent of all patients seen during this same period of time with malignant salivary gland tumors. No specific etiologic factors were implicated except that the tumors occurred predominantly in white males. The overall results of treatment were poor, perhaps secondary to delay in diagnosis, very biologically aggressive tumors, or inadequate or improper treatment. Hopefully, the 20 per cent survival can be improved with planned combined sequential surgery and radiation in those selected high risk patients.", "contents": "Malignant salivary gland neoplasms of the lip. The charts of fourteen patients with malignant salivary gland tumors of the lip were reviewed. These patients represented 1 per cent of all patients seen during this same period of time with malignant salivary gland tumors. No specific etiologic factors were implicated except that the tumors occurred predominantly in white males. The overall results of treatment were poor, perhaps secondary to delay in diagnosis, very biologically aggressive tumors, or inadequate or improper treatment. Hopefully, the 20 per cent survival can be improved with planned combined sequential surgery and radiation in those selected high risk patients."}
{"id": "PMID:199090", "title": "Pattern of angiomas in the Igbos of Nigeria.", "content": "Almost all angiomas fall into three main groups--hemangioma, lymphangioma, and glomangioma. Fifty-one such angiomas were found in approximately 7500 surgical specimens examined at a central laboratory serving the Igbos of Nigeria. The youngest patient was aged 19 days and the oldest 70 years. Most patients presented in the first two decades of life and both sexes were equally affected. Hemangiomas greatly outnumbered the other angiomas; most were cavernous and tended to thrombose, fibrose, or calcify. Lymphangiomas frequently exhibited lymphoid tissue, some showing germinal centers. Glomangiomas occurred mostly in the upper extremity as small, painful masses.", "contents": "Pattern of angiomas in the Igbos of Nigeria. Almost all angiomas fall into three main groups--hemangioma, lymphangioma, and glomangioma. Fifty-one such angiomas were found in approximately 7500 surgical specimens examined at a central laboratory serving the Igbos of Nigeria. The youngest patient was aged 19 days and the oldest 70 years. Most patients presented in the first two decades of life and both sexes were equally affected. Hemangiomas greatly outnumbered the other angiomas; most were cavernous and tended to thrombose, fibrose, or calcify. Lymphangiomas frequently exhibited lymphoid tissue, some showing germinal centers. Glomangiomas occurred mostly in the upper extremity as small, painful masses."}
{"id": "PMID:199092", "title": "Temporary remission of hypoglycemia in a dog with an insulinoma after treatment with streptozotocin.", "content": "Temporary remission of hypoglycemia was achieved in a dog with an insulinoma by treatment, using streptozotocin. Nephropathy, manifested as a renal tubular defect, and hepatopathy were associated with the administration of streptozotocin.", "contents": "Temporary remission of hypoglycemia in a dog with an insulinoma after treatment with streptozotocin. Temporary remission of hypoglycemia was achieved in a dog with an insulinoma by treatment, using streptozotocin. Nephropathy, manifested as a renal tubular defect, and hepatopathy were associated with the administration of streptozotocin."}
{"id": "PMID:199093", "title": "Equine rhinopneumonitis virus (herpesvirus type 1): attenuation in stable monkey cell line.", "content": "An isolate of virulent equine herpesvirus (EHV) type 1 was adapted to Vero stable cell line by 13 serial passages at 37 C and 50 serial passages at 26 C. Characteristics of the attenuated EHV-1 were found to be avirulent, but immunogenic in horses if injected intramuscularly. The attenuated virus was regularly isolated from peripheral leukocytes in inoculated horses, but was not recovered from nasal turbinate tissues. A mild leukopenia was noticed. The attenuated virus produced characteristic large syncytia on primary isolation in rabbit kidney (RK13) or Vero cells at 37 C in contrast to cell rounding observed with virulent EHV-1. The syncytial marker was stable through 20 serial passages in Vero cells at 37 C. New application of double immunodiffusion test for distinguishing between EHV-1 and EHV-2 also is described.", "contents": "Equine rhinopneumonitis virus (herpesvirus type 1): attenuation in stable monkey cell line. An isolate of virulent equine herpesvirus (EHV) type 1 was adapted to Vero stable cell line by 13 serial passages at 37 C and 50 serial passages at 26 C. Characteristics of the attenuated EHV-1 were found to be avirulent, but immunogenic in horses if injected intramuscularly. The attenuated virus was regularly isolated from peripheral leukocytes in inoculated horses, but was not recovered from nasal turbinate tissues. A mild leukopenia was noticed. The attenuated virus produced characteristic large syncytia on primary isolation in rabbit kidney (RK13) or Vero cells at 37 C in contrast to cell rounding observed with virulent EHV-1. The syncytial marker was stable through 20 serial passages in Vero cells at 37 C. New application of double immunodiffusion test for distinguishing between EHV-1 and EHV-2 also is described."}
{"id": "PMID:199094", "title": "Inactivation of equine infectious anemia virus by chemical disinfectants.", "content": "Twelve chemicals and commercial disinfectants were tested for inactivation of equine infectious anemia virus. In the presence of 10% bovine serum, all chemicals inactivated 4 log10 (based on 0.1 ml) of the virus within 5 minutes at 23 C. A reduction of at least 4 log10 was observed when the virus was exposed for 1 minute to substituted phenolic disinfectants (3 commercial preparations and sodium orthophenylphenate), halogen derivatives (iodophor and sodium hypochlorite), chlorhexidine, and 70% ethanol. Sodium hydroxide (5%), 2% formalin, and 2% glutaraldehyde were slower to inactivate the virus, but achieved 4 log10 reduction in titer by 5 minutes' contact time. The susceptibility of the equine infectious anemia virus to chemical disinfectants is similar to that of other enveloped viruses.", "contents": "Inactivation of equine infectious anemia virus by chemical disinfectants. Twelve chemicals and commercial disinfectants were tested for inactivation of equine infectious anemia virus. In the presence of 10% bovine serum, all chemicals inactivated 4 log10 (based on 0.1 ml) of the virus within 5 minutes at 23 C. A reduction of at least 4 log10 was observed when the virus was exposed for 1 minute to substituted phenolic disinfectants (3 commercial preparations and sodium orthophenylphenate), halogen derivatives (iodophor and sodium hypochlorite), chlorhexidine, and 70% ethanol. Sodium hydroxide (5%), 2% formalin, and 2% glutaraldehyde were slower to inactivate the virus, but achieved 4 log10 reduction in titer by 5 minutes' contact time. The susceptibility of the equine infectious anemia virus to chemical disinfectants is similar to that of other enveloped viruses."}
{"id": "PMID:199095", "title": "Leukocyte migration-inhibition procedure for transmissible gastroenteritis viral antigens.", "content": "Swine exposed to transmissible gastroenteritis viral antigens developed humoral and cell-mediated immunity. Migration of leukocytes from exposed swine was inhibited in the presence of the sensitizing antigens, whereas migration of leukocytes from nonexposed swine was not inhibited in the presense of these same antigens. In virus-neutralization-positive animals, it was not possible to correlate degree of inhibition with virus-neutralization titer. Inhibition was observed 7 days after exposure and was found to persist for at least 35 days.", "contents": "Leukocyte migration-inhibition procedure for transmissible gastroenteritis viral antigens. Swine exposed to transmissible gastroenteritis viral antigens developed humoral and cell-mediated immunity. Migration of leukocytes from exposed swine was inhibited in the presence of the sensitizing antigens, whereas migration of leukocytes from nonexposed swine was not inhibited in the presense of these same antigens. In virus-neutralization-positive animals, it was not possible to correlate degree of inhibition with virus-neutralization titer. Inhibition was observed 7 days after exposure and was found to persist for at least 35 days."}
{"id": "PMID:199096", "title": "Diabetes, blood lipids, and the role of obesity in coronary heart disease risk for women. The Framingham study.", "content": "Diabetes and a low high-density lipoprotein cholesterol level are associated with each other and with a higher coronary heart disease risk in women. Moreover, both are strongly associated with obesity. These findings are reported from the Framington Study, in which persons aged 49 to 82 were characterized, after overnight fast, for blood lipids by the method of Fredrickson and Levy and then followed for the subsequent development of coronary heart disease. Low-density lipoprotein cholesterol was also associated with coronary heart disease risk in women, but fasting triglycerides were not associated with risk after allowing for the association with high-density lipoprotein cholesterol and diabetes. A low high-density lipoprotein cholesterol in the presence of diabetes appeared to raise the coronary heart disease risk in women relative to that of men.", "contents": "Diabetes, blood lipids, and the role of obesity in coronary heart disease risk for women. The Framingham study. Diabetes and a low high-density lipoprotein cholesterol level are associated with each other and with a higher coronary heart disease risk in women. Moreover, both are strongly associated with obesity. These findings are reported from the Framington Study, in which persons aged 49 to 82 were characterized, after overnight fast, for blood lipids by the method of Fredrickson and Levy and then followed for the subsequent development of coronary heart disease. Low-density lipoprotein cholesterol was also associated with coronary heart disease risk in women, but fasting triglycerides were not associated with risk after allowing for the association with high-density lipoprotein cholesterol and diabetes. A low high-density lipoprotein cholesterol in the presence of diabetes appeared to raise the coronary heart disease risk in women relative to that of men."}
{"id": "PMID:199097", "title": "Arthritis associated with apatite crystals.", "content": "Needle-shaped crystals of 75 to 250 A diameter have been identified by transmission electron microscopy in clumps within synovial fluid mononuclear cell vacuoles in a variety of joint diseases. These crystals, similar to those previously associated with calcific periarthritis, were seen in acute undiagnosed arthritis and in exacerbations of osteoarthritis where they may be inducing a synovitis similar to that seen with urate and pyrophosphate crystals in gout and pseudogout. By light microscopy purple staining cytoplasmic inclusions or extracellular globules can suggest the presence of clumps of these crystals. Apatite clumps can also occasionally appear as small birefringent chunks or rods and thus might mimic urate or calcium pyrophosphate. Ultrastructural appearance, electron probe analysis, and X-ray diffraction pattern were those of apatite. Experimental injection of hydroxyapatite crystals into dog knee joints produces inflammation supporting the potential role for these crystals in joint disease.", "contents": "Arthritis associated with apatite crystals. Needle-shaped crystals of 75 to 250 A diameter have been identified by transmission electron microscopy in clumps within synovial fluid mononuclear cell vacuoles in a variety of joint diseases. These crystals, similar to those previously associated with calcific periarthritis, were seen in acute undiagnosed arthritis and in exacerbations of osteoarthritis where they may be inducing a synovitis similar to that seen with urate and pyrophosphate crystals in gout and pseudogout. By light microscopy purple staining cytoplasmic inclusions or extracellular globules can suggest the presence of clumps of these crystals. Apatite clumps can also occasionally appear as small birefringent chunks or rods and thus might mimic urate or calcium pyrophosphate. Ultrastructural appearance, electron probe analysis, and X-ray diffraction pattern were those of apatite. Experimental injection of hydroxyapatite crystals into dog knee joints produces inflammation supporting the potential role for these crystals in joint disease."}
{"id": "PMID:199098", "title": "Serum angiotensin-converting enzyme in leprosy and coccidioidomycosis.", "content": "Serum angiotensin-converting enzyme levels were found to be elevated in 71.4% of 42 leprosy patients, both treated and untreated, but in only one of 13 patients with disseminated coccidioidomycosis. The elevations with leprosy were present in association with each of the three major categories: lepromatous, borderline, or tuberculoid. Sulfone therapy had no immediate effect on the elevated serum levels, although long-term sulfone therapy appeared to result in lowering of the level. Corticosteroid therapy had a more immediate and dramatic effect on reducing the elevated angiotensin-converting enzyme level in leprosy. This assay cannot distinguish between sarcoidosis and leprosy or between the various categories of leprosy, but it can help differentiate sarcoidosis from fungal or tuberculous disease. Elevated levels of serum angiotensin-converting enzyme have now been associated with three diseases states: sarcoidosis, Gaucher's disease, and leprosy.", "contents": "Serum angiotensin-converting enzyme in leprosy and coccidioidomycosis. Serum angiotensin-converting enzyme levels were found to be elevated in 71.4% of 42 leprosy patients, both treated and untreated, but in only one of 13 patients with disseminated coccidioidomycosis. The elevations with leprosy were present in association with each of the three major categories: lepromatous, borderline, or tuberculoid. Sulfone therapy had no immediate effect on the elevated serum levels, although long-term sulfone therapy appeared to result in lowering of the level. Corticosteroid therapy had a more immediate and dramatic effect on reducing the elevated angiotensin-converting enzyme level in leprosy. This assay cannot distinguish between sarcoidosis and leprosy or between the various categories of leprosy, but it can help differentiate sarcoidosis from fungal or tuberculous disease. Elevated levels of serum angiotensin-converting enzyme have now been associated with three diseases states: sarcoidosis, Gaucher's disease, and leprosy."}
{"id": "PMID:199099", "title": "Hypersensitivity to adrenergic stimulation after propranolol withdrawal in normal subjects.", "content": "The cardiac response to isoproterenol after propranolol withdrawal was studied in six normal persons. Serial isoproterenol infusions were done before and after oral propranolol administration, 160 mg daily for 2 days. Changes in electromechanical systole corrected for heart rate (QS2I) and pulse pressure were used to assess the inotropic response to isoproterenol, and changes in heart rate were used to assess the chronotropic response. As shown in previous studies, the negative inotropic effect of propranolol lasted only 12 to 15 h, while the negative chronotropic effect lasted 24 to 36 h. After the disappearance of blockade a hypersensitivity to isoproterenol was found 24 to 48 h after propranolol withdrawal in all three measured determinants. The explanation of this phenomenon most likely lies in the nature of adrenergic receptors that become activated during long-term blockade.", "contents": "Hypersensitivity to adrenergic stimulation after propranolol withdrawal in normal subjects. The cardiac response to isoproterenol after propranolol withdrawal was studied in six normal persons. Serial isoproterenol infusions were done before and after oral propranolol administration, 160 mg daily for 2 days. Changes in electromechanical systole corrected for heart rate (QS2I) and pulse pressure were used to assess the inotropic response to isoproterenol, and changes in heart rate were used to assess the chronotropic response. As shown in previous studies, the negative inotropic effect of propranolol lasted only 12 to 15 h, while the negative chronotropic effect lasted 24 to 36 h. After the disappearance of blockade a hypersensitivity to isoproterenol was found 24 to 48 h after propranolol withdrawal in all three measured determinants. The explanation of this phenomenon most likely lies in the nature of adrenergic receptors that become activated during long-term blockade."}
{"id": "PMID:199100", "title": "Alveolar cell carcinoma in identical twins. Similarity in time of onset, histochemistry, and site of metastasis.", "content": "Identical male twins had alveolar cell carcinoma with nearly synchronous onset and similar histopathologic features, both metastatic to the brain. The hypothesis is advanced that there are genes shared by these twins that determine not only the susceptibility of pulmonary cells to malignant transformation but also the character of the resultant neoplasm, including its histologic features and metastatic behavior.", "contents": "Alveolar cell carcinoma in identical twins. Similarity in time of onset, histochemistry, and site of metastasis. Identical male twins had alveolar cell carcinoma with nearly synchronous onset and similar histopathologic features, both metastatic to the brain. The hypothesis is advanced that there are genes shared by these twins that determine not only the susceptibility of pulmonary cells to malignant transformation but also the character of the resultant neoplasm, including its histologic features and metastatic behavior."}
{"id": "PMID:199101", "title": "[Plasmidic resistance of \"Haemophilus sp.\" to aminoglycoside antibiotics: isolation and study of a new phosphotransferase (author's transl)].", "content": "Plasmid mediated phosphorylating activities have been found in Haemophilus sp. strains resistant to some aminoglycoside antibiotics. The enzymes responsible for this phenomenon have been purified and studied. They belong to the group of aminoglycoside phosphotransferases which are able to phosphorylate these antibiotics on the 3'- or 5\"-hydroxyl group. The first enzyme studied is closely related to APH(3')I whereas the second one is different from the former on the basis of substrate specificities and physicochemical properties. We propose to call this second enzyme APH(3')Ib as compared to APH(3')I which will be called APH(3')Ia.", "contents": "[Plasmidic resistance of \"Haemophilus sp.\" to aminoglycoside antibiotics: isolation and study of a new phosphotransferase (author's transl)]. Plasmid mediated phosphorylating activities have been found in Haemophilus sp. strains resistant to some aminoglycoside antibiotics. The enzymes responsible for this phenomenon have been purified and studied. They belong to the group of aminoglycoside phosphotransferases which are able to phosphorylate these antibiotics on the 3'- or 5\"-hydroxyl group. The first enzyme studied is closely related to APH(3')I whereas the second one is different from the former on the basis of substrate specificities and physicochemical properties. We propose to call this second enzyme APH(3')Ib as compared to APH(3')I which will be called APH(3')Ia."}
{"id": "PMID:199108", "title": "[Effect of different salts and their concentration on polymyxin M biosynthesis by Bac. polymyxa Ross].", "content": "The effect of various concentrations of ammonium sulfate, sodium and potassium chlorides and sulfates on biosynthesis of polymyxin M by Bac. polymyxa Ross. on media containing wheet meal as the carbon source was studied. The culture growth, antibiotic accumulation and consumption of the main nutrients was studied as dependent on the level of the salts in the medium. The highest productivity was observed on media with the salt concentrations amounting to 1--2 per cent except sodium sulfate: changes in the concentration of the latter had practically no effect on the activity of the fermentation broth.", "contents": "[Effect of different salts and their concentration on polymyxin M biosynthesis by Bac. polymyxa Ross]. The effect of various concentrations of ammonium sulfate, sodium and potassium chlorides and sulfates on biosynthesis of polymyxin M by Bac. polymyxa Ross. on media containing wheet meal as the carbon source was studied. The culture growth, antibiotic accumulation and consumption of the main nutrients was studied as dependent on the level of the salts in the medium. The highest productivity was observed on media with the salt concentrations amounting to 1--2 per cent except sodium sulfate: changes in the concentration of the latter had practically no effect on the activity of the fermentation broth."}
{"id": "PMID:199109", "title": "[Nerve-blocking properties of antibiotics].", "content": "Comparative data on the neuroblocking activity of antibiotics of various groups in acute experiments on albino mice and narcotized cats are presented. It was found that according to the impairments in the neuro-muscle conductivity the drugs were arranged in the following descending order: polymyxin B, neomycin, gentamicin, streptomycin, lincomycin and kanamycin. The streptomycin derivatives were approximately 2 times less toxic than streptomycin. The problems of the mode of action of the antibiotics on conductivity of excitation in the neuro-muscle synapses are discussed.", "contents": "[Nerve-blocking properties of antibiotics]. Comparative data on the neuroblocking activity of antibiotics of various groups in acute experiments on albino mice and narcotized cats are presented. It was found that according to the impairments in the neuro-muscle conductivity the drugs were arranged in the following descending order: polymyxin B, neomycin, gentamicin, streptomycin, lincomycin and kanamycin. The streptomycin derivatives were approximately 2 times less toxic than streptomycin. The problems of the mode of action of the antibiotics on conductivity of excitation in the neuro-muscle synapses are discussed."}
{"id": "PMID:199110", "title": "Rapid detection and quantitation of Clostridium perfringens enterostoxin by counterimmunoelectrophoresis.", "content": "Conditions for detection and quantitation of Clostridium perfringens enterotoxin by counterimmunoelectrophoresis are described. As little as 0.2 microgram of enterotoxin per ml could be detected. The test was found to be rapid, sensitive, specific and easy for the detection and quantitation of enterotoxin.", "contents": "Rapid detection and quantitation of Clostridium perfringens enterostoxin by counterimmunoelectrophoresis. Conditions for detection and quantitation of Clostridium perfringens enterotoxin by counterimmunoelectrophoresis are described. As little as 0.2 microgram of enterotoxin per ml could be detected. The test was found to be rapid, sensitive, specific and easy for the detection and quantitation of enterotoxin."}
{"id": "PMID:199111", "title": "Increased spore yields of Clostridium perfringens in the presence of methylxanthines.", "content": "The methylxanthines caffeine, theophylline, and isobutylmethylxanthine greatly increased spore yields of Clostridium perfringens strains FD-1, PS52, and PS49 when grown on Duncan-Strong medium or on a new casein-digest medium. Four other strains (KA3, and National Collection of Type Cultures strains 8798, 8238, and 10240) failed to show any significant increase when tested under similar conditions. The degree of sporulation increase was influenced by the carbohydrate energy source in some strains but not in others. Strain PS52 showed a large increase in spore yield when dextrin was the energy source but only a slight increase when raffinose served as the energy source. Strain FD-1 showed similar increases in spore yield with either dextrin or raffinose.", "contents": "Increased spore yields of Clostridium perfringens in the presence of methylxanthines. The methylxanthines caffeine, theophylline, and isobutylmethylxanthine greatly increased spore yields of Clostridium perfringens strains FD-1, PS52, and PS49 when grown on Duncan-Strong medium or on a new casein-digest medium. Four other strains (KA3, and National Collection of Type Cultures strains 8798, 8238, and 10240) failed to show any significant increase when tested under similar conditions. The degree of sporulation increase was influenced by the carbohydrate energy source in some strains but not in others. Strain PS52 showed a large increase in spore yield when dextrin was the energy source but only a slight increase when raffinose served as the energy source. Strain FD-1 showed similar increases in spore yield with either dextrin or raffinose."}
{"id": "PMID:199112", "title": "Dialysis technique for containment of microbial populations inoculated into food systems.", "content": "A technique utilizing dialysis tubing was developed for the containment of microbial populations introduced into a food system. The entrapment of the inoculum was accomplished while reducing interference with interactions between the sample and the surrounding environment.", "contents": "Dialysis technique for containment of microbial populations inoculated into food systems. A technique utilizing dialysis tubing was developed for the containment of microbial populations introduced into a food system. The entrapment of the inoculum was accomplished while reducing interference with interactions between the sample and the surrounding environment."}
{"id": "PMID:199113", "title": "Thermal inactivation of ileal loop-reactive Clostridium perfringens type A strains in phosphate buffer and beef gravy.", "content": "The thermal resistance of spore crops produced from each of two ileal loop-reactive strains of Clostridium perfringens type A was determined in two suspending vehicles consisting of 0.067 M (pH 7.0) phosphate buffer and a commercial beef gravy. D115.6 values obtained in buffer and enumerated after pretreatment with sodium ethylenediaminetetraacetate and recovery in plating medium containing lysozyme were two- to threefold greater than those obtained without this treatment. D115.6 values obtained with beef gravy were less than those obtained in buffer with or without lysozyme; however, the D98.9 and D104.4 values were 1.3 to 2 times greater than those obtained in buffer with lysozyme. The z values were within the ranges reported by previous investigators.", "contents": "Thermal inactivation of ileal loop-reactive Clostridium perfringens type A strains in phosphate buffer and beef gravy. The thermal resistance of spore crops produced from each of two ileal loop-reactive strains of Clostridium perfringens type A was determined in two suspending vehicles consisting of 0.067 M (pH 7.0) phosphate buffer and a commercial beef gravy. D115.6 values obtained in buffer and enumerated after pretreatment with sodium ethylenediaminetetraacetate and recovery in plating medium containing lysozyme were two- to threefold greater than those obtained without this treatment. D115.6 values obtained with beef gravy were less than those obtained in buffer with or without lysozyme; however, the D98.9 and D104.4 values were 1.3 to 2 times greater than those obtained in buffer with lysozyme. The z values were within the ranges reported by previous investigators."}
{"id": "PMID:199114", "title": "Arenavirus concentration by molecular filtration.", "content": "Liter volumes of a human arenavirus pathogen (Machupo) and a nonpathogen (Tacaribe) were concentrated 30 to 100 times in less than 90 min without significant loss of particle infectivity.", "contents": "Arenavirus concentration by molecular filtration. Liter volumes of a human arenavirus pathogen (Machupo) and a nonpathogen (Tacaribe) were concentrated 30 to 100 times in less than 90 min without significant loss of particle infectivity."}
{"id": "PMID:199118", "title": "Synthesis of prostaglandins by psoriatic skin.", "content": "The biosynthesis of prostaglandins (PG) in biopsies from 9 patients with psoriasis was studied. The involved as well as the uninvolved psoriatic skin showed a statistically significant decrease of the ability to synthesize PG's. In PGE1-equivalents the concentration (mean +/- S.E.M.) was 4.41 +/- 0.48 ng/g wet weight in the psoriatic lesion, 5.41 +/- 0.64 ng/g wet weight in uninvolved psoriatic skin in the presence of exogenous arachidonic acid in the incubation medium as compared with 9.02 +/- 1.59 in normal human skin. When the skin was incubated without excess of exogenous precursor acid the activity formed was similarly significantly lower in psoriatic skin as compared with normal skin. A disturbed balance between E and F PG synthesis was not demonstrated, which might have accounted for the postulated altered intracellular ratio of cyclic AMP to cyclic GMP in psoriatic skin.", "contents": "Synthesis of prostaglandins by psoriatic skin. The biosynthesis of prostaglandins (PG) in biopsies from 9 patients with psoriasis was studied. The involved as well as the uninvolved psoriatic skin showed a statistically significant decrease of the ability to synthesize PG's. In PGE1-equivalents the concentration (mean +/- S.E.M.) was 4.41 +/- 0.48 ng/g wet weight in the psoriatic lesion, 5.41 +/- 0.64 ng/g wet weight in uninvolved psoriatic skin in the presence of exogenous arachidonic acid in the incubation medium as compared with 9.02 +/- 1.59 in normal human skin. When the skin was incubated without excess of exogenous precursor acid the activity formed was similarly significantly lower in psoriatic skin as compared with normal skin. A disturbed balance between E and F PG synthesis was not demonstrated, which might have accounted for the postulated altered intracellular ratio of cyclic AMP to cyclic GMP in psoriatic skin."}
{"id": "PMID:199119", "title": "Assessment of the role of surgery for control of lung cancer.", "content": "When morphologically stratified, the classification of patients according to surgical stage provides an objective basis for evaluating the results of surgical treatment. In a review of 794 patients according to surgical staging criteria, the data supported concepts regarding differences in the behavior of each cell type as well as major differences in survival between each stage of disease. The overall cumulative five-year survival was 37% for squamous cell carcinoma, 27% for adenocarcinoma, and 27% for undifferentiated large cell carcinoma. Fewer than 1% of patients with undifferentiated small cell carcinoma survived. Survival for patients with surgical Stage I disease was 53%, for Stage II 29%, and for Stage III 16%. The results of surgical treatment for patients with limited disease extent are much better than is generally realized. Fifty to 60% of such patients in this series survived five years. Survival studies by surgical stage permit resonable estimates of the presence of occult metastatic disease and supply insights necessary to the design and appropriate selection of adjunctive therapeutic programs.", "contents": "Assessment of the role of surgery for control of lung cancer. When morphologically stratified, the classification of patients according to surgical stage provides an objective basis for evaluating the results of surgical treatment. In a review of 794 patients according to surgical staging criteria, the data supported concepts regarding differences in the behavior of each cell type as well as major differences in survival between each stage of disease. The overall cumulative five-year survival was 37% for squamous cell carcinoma, 27% for adenocarcinoma, and 27% for undifferentiated large cell carcinoma. Fewer than 1% of patients with undifferentiated small cell carcinoma survived. Survival for patients with surgical Stage I disease was 53%, for Stage II 29%, and for Stage III 16%. The results of surgical treatment for patients with limited disease extent are much better than is generally realized. Fifty to 60% of such patients in this series survived five years. Survival studies by surgical stage permit resonable estimates of the presence of occult metastatic disease and supply insights necessary to the design and appropriate selection of adjunctive therapeutic programs."}
{"id": "PMID:199120", "title": "Dissociation of lipolysis from the levels of cyclic AMP in rat epididymal fat cells.", "content": "Two compounds, theophylline and 8-aza-9-furfuryl-adenine (SQ 4665), were found to maximally stimulate lipolysis in preparations of rat epididymal fat cells in the absence of exogenous hormones. Cyclic AMP levels in lipocytes maximally stimulated by either agent alone were unchanged from control levels. In contrast, lipolysis stimulated by either epinephrine alone or in combination with several cyclic nucleotide phosphodiesterase inhibitors correlated well with increases in the levels of cyclic AMP observed. These results suggest the presence of a non-cyclic AMP dependent pathway for the stimulation of lipolysis in rat epididymal fat cells.", "contents": "Dissociation of lipolysis from the levels of cyclic AMP in rat epididymal fat cells. Two compounds, theophylline and 8-aza-9-furfuryl-adenine (SQ 4665), were found to maximally stimulate lipolysis in preparations of rat epididymal fat cells in the absence of exogenous hormones. Cyclic AMP levels in lipocytes maximally stimulated by either agent alone were unchanged from control levels. In contrast, lipolysis stimulated by either epinephrine alone or in combination with several cyclic nucleotide phosphodiesterase inhibitors correlated well with increases in the levels of cyclic AMP observed. These results suggest the presence of a non-cyclic AMP dependent pathway for the stimulation of lipolysis in rat epididymal fat cells."}
{"id": "PMID:199121", "title": "Vascular alpha adrenotropic responses of the isolated rabbit kidney at 15 degrees C.", "content": "Rabbit kidneys were isolated and perfused with a balanced salt solution at 15 degrees C. The effects of norepinephrine (NOR) and phentolamine (P) were tested after fastly or slowly induced cooling. Vascular alpha receptor effects were enhanced by a slow cooling rate (0.6 degrees C/min), but blocked or impaired by a faster cooling rate (6 degrees C/min). Kidney function was severely impaired at this temperature as it would be expected.", "contents": "Vascular alpha adrenotropic responses of the isolated rabbit kidney at 15 degrees C. Rabbit kidneys were isolated and perfused with a balanced salt solution at 15 degrees C. The effects of norepinephrine (NOR) and phentolamine (P) were tested after fastly or slowly induced cooling. Vascular alpha receptor effects were enhanced by a slow cooling rate (0.6 degrees C/min), but blocked or impaired by a faster cooling rate (6 degrees C/min). Kidney function was severely impaired at this temperature as it would be expected."}
{"id": "PMID:199122", "title": "[Precipitation antibodies against poliovirus in patients with poliomyelitis].", "content": "Sera from 26 children bearing poliomyelitis caused by virus tipe I and from 47 cases with paralysis of different etiology (non-poliomyelitic) were tested against antigen of poliovirus types I, II and III with an agar-immunoprecipitation reaction. All sera with neutralizing antibodies with titres of 1:1250 gave positive results in immunodifusion tests. The percentage of positiveness decrease with lower titres. No false positive reactions were found. Immunodiffusion test with antigens of poliovirus were positive in 100% of sera from patients with poliomyelitis and only in 30% in sera from patients with non polio paralysis.", "contents": "[Precipitation antibodies against poliovirus in patients with poliomyelitis]. Sera from 26 children bearing poliomyelitis caused by virus tipe I and from 47 cases with paralysis of different etiology (non-poliomyelitic) were tested against antigen of poliovirus types I, II and III with an agar-immunoprecipitation reaction. All sera with neutralizing antibodies with titres of 1:1250 gave positive results in immunodifusion tests. The percentage of positiveness decrease with lower titres. No false positive reactions were found. Immunodiffusion test with antigens of poliovirus were positive in 100% of sera from patients with poliomyelitis and only in 30% in sera from patients with non polio paralysis."}
{"id": "PMID:199123", "title": "[Cytochemical labeling of proteolytic enzymes in Entamoeba histolytica].", "content": "Trophozoites were obtained from fecal mucous in patients bearing colonic amebiasis. The tripsin inhibitor of soya bean was coupled to peroxidase according to Nakane and Kawokoi method. Amebae were incubated with couple and reactions were developed following Karnowsky's technic. There was a specific labeling of proteolitic enzymes on plasma membrane, the wall of digestive vacuoles and intracytoplasmic vacuoles of the trophozoites. Such a distribution of proteolitic enzymes agreed with digestive and invasion functions of E. histolytica.", "contents": "[Cytochemical labeling of proteolytic enzymes in Entamoeba histolytica]. Trophozoites were obtained from fecal mucous in patients bearing colonic amebiasis. The tripsin inhibitor of soya bean was coupled to peroxidase according to Nakane and Kawokoi method. Amebae were incubated with couple and reactions were developed following Karnowsky's technic. There was a specific labeling of proteolitic enzymes on plasma membrane, the wall of digestive vacuoles and intracytoplasmic vacuoles of the trophozoites. Such a distribution of proteolitic enzymes agreed with digestive and invasion functions of E. histolytica."}
{"id": "PMID:199125", "title": "Induction of polymyxin resistance in Pseudomonas fluorescens by phosphate limitation.", "content": "Shift of Pseudomonas fluorescens NCMB 129 from a a phosphate rich into a phosphate limited medium results in a reduction of the membrane phospholipids phosphatidylethanolamine, phosphatidylglycerol and cardiolipin. Concomitantly a positively charged ornithine amide lipid is synthesized. The gradual increase of this lipid is paralleled by an increasing resistance to polymyxin B. The binding capacities of intact cells, and isolated inner and outer membranes for the antibiotic are reduced in the resistant organisms. It is discussed that the observed effect could be circumstantial evidence that the positively charged polymyxin B needs negatively charged receptors in biological membranes in order to exert its antibiotic activity.", "contents": "Induction of polymyxin resistance in Pseudomonas fluorescens by phosphate limitation. Shift of Pseudomonas fluorescens NCMB 129 from a a phosphate rich into a phosphate limited medium results in a reduction of the membrane phospholipids phosphatidylethanolamine, phosphatidylglycerol and cardiolipin. Concomitantly a positively charged ornithine amide lipid is synthesized. The gradual increase of this lipid is paralleled by an increasing resistance to polymyxin B. The binding capacities of intact cells, and isolated inner and outer membranes for the antibiotic are reduced in the resistant organisms. It is discussed that the observed effect could be circumstantial evidence that the positively charged polymyxin B needs negatively charged receptors in biological membranes in order to exert its antibiotic activity."}
{"id": "PMID:199126", "title": "Micromorphology of Gram-negative hydrogen bacteria. II. Cell envelope, membranes, and cytoplasmic inclusions.", "content": "The fine structure of the cell envelope, of membrane systems and of cytoplasmic inclusions of Gram-negative aerobic hydrogen bacteria has been studied. The results have been tabulated, and three main groups could be recognized: Group 1: Alcaligenes eutrophus, A.paradoxus, A.ruhlandii, Pseudomonas facilis,   P.flava, P.pseudoflava, P.palleronii, and Aquaspirillum autotrophicum; Group 2: \"Corynebacterium\" autotrophicum and strains MA 2 and SA 35; Group 3: Paracoccus denitrificans. Special structures related to the chemoautotrophic way of life of the hydrogen bacteria were not observed.", "contents": "Micromorphology of Gram-negative hydrogen bacteria. II. Cell envelope, membranes, and cytoplasmic inclusions. The fine structure of the cell envelope, of membrane systems and of cytoplasmic inclusions of Gram-negative aerobic hydrogen bacteria has been studied. The results have been tabulated, and three main groups could be recognized: Group 1: Alcaligenes eutrophus, A.paradoxus, A.ruhlandii, Pseudomonas facilis,   P.flava, P.pseudoflava, P.palleronii, and Aquaspirillum autotrophicum; Group 2: \"Corynebacterium\" autotrophicum and strains MA 2 and SA 35; Group 3: Paracoccus denitrificans. Special structures related to the chemoautotrophic way of life of the hydrogen bacteria were not observed."}
{"id": "PMID:199128", "title": "Evidence against involvement of endorphins in sexual arousal and orgasm in man.", "content": "In a double-blind study, intravenous injection of naloxone, at a dose sufficient to saturate the opiate (endorphin) receptors, had no effect on sexual arousal, penile erection, ejaculation, or orgasm in a human subject. Apparently, endorphins are not involved in these phenomena.", "contents": "Evidence against involvement of endorphins in sexual arousal and orgasm in man. In a double-blind study, intravenous injection of naloxone, at a dose sufficient to saturate the opiate (endorphin) receptors, had no effect on sexual arousal, penile erection, ejaculation, or orgasm in a human subject. Apparently, endorphins are not involved in these phenomena."}
{"id": "PMID:199129", "title": "Fluphenazine decanoate, oral fluphenazine, and placebo in treatment of remitted schizophrenics. II. Rating scale data.", "content": "This study of patients with remitted chronic schizophrenia in an aftercare clinic was designed to test whether such patients require maintenance antipsychotic medication. A previous report showed that the group receiving active medication, fluphenazine decanoate and oral fluphenazine, had far fewer relapses; but the former group had a high incidence of akinesia. This present report presents rating scale data substantiating these two findings: (1) patients terminated on clinical grounds because of a schizophrenic relapse showed rating scale changes consistent with that diagnosis; and (2) the patients removed due to severe akinesia showed a worsening on items selected a priori to measure akinesia, and when compared to survivors on the same items, showed significant differences--thus confirming our clinical judgments.", "contents": "Fluphenazine decanoate, oral fluphenazine, and placebo in treatment of remitted schizophrenics. II. Rating scale data. This study of patients with remitted chronic schizophrenia in an aftercare clinic was designed to test whether such patients require maintenance antipsychotic medication. A previous report showed that the group receiving active medication, fluphenazine decanoate and oral fluphenazine, had far fewer relapses; but the former group had a high incidence of akinesia. This present report presents rating scale data substantiating these two findings: (1) patients terminated on clinical grounds because of a schizophrenic relapse showed rating scale changes consistent with that diagnosis; and (2) the patients removed due to severe akinesia showed a worsening on items selected a priori to measure akinesia, and when compared to survivors on the same items, showed significant differences--thus confirming our clinical judgments."}
{"id": "PMID:199130", "title": "Life events and schizophrenia. I. Comparison of schizophrenics with a community sample.", "content": "In exploring the relationship of life events and psychiatric impairment in a group of 132 posthospitalized schizophrenics living in the community, schizophrenics are contrasted with 132 nonpatient community subjects matched on age, race, sex, and social class. Schizophrenics were significantly more psychiatrically impaired than their nonpatient counterparts and experienced significantly more life events. The overall correlation between life events and psychiatric impairment is weaker in the schizophrenic group than in the control group. However, our findings underscore the association between these variables found in previous studies. In terms of specificity, schizophrenics experienced significantly more events in the interpersonal, health, work, legal, and community crisis areas of activity, and more events categorized as exits from the social field and socially undesirable. On the psychological control dimension, schizophrenics experienced significantly more life events categorized both as \"controlled\" and \"uncontrolled\". We discuss the findings in relation to studies exploring the relationship of life events to illness onset and show the implications for the delivery of mental health services to schizophrenics living in the community setting.", "contents": "Life events and schizophrenia. I. Comparison of schizophrenics with a community sample. In exploring the relationship of life events and psychiatric impairment in a group of 132 posthospitalized schizophrenics living in the community, schizophrenics are contrasted with 132 nonpatient community subjects matched on age, race, sex, and social class. Schizophrenics were significantly more psychiatrically impaired than their nonpatient counterparts and experienced significantly more life events. The overall correlation between life events and psychiatric impairment is weaker in the schizophrenic group than in the control group. However, our findings underscore the association between these variables found in previous studies. In terms of specificity, schizophrenics experienced significantly more events in the interpersonal, health, work, legal, and community crisis areas of activity, and more events categorized as exits from the social field and socially undesirable. On the psychological control dimension, schizophrenics experienced significantly more life events categorized both as \"controlled\" and \"uncontrolled\". We discuss the findings in relation to studies exploring the relationship of life events to illness onset and show the implications for the delivery of mental health services to schizophrenics living in the community setting."}
{"id": "PMID:199131", "title": "[On the organization of the mature human placenta (author's transl)].", "content": "By means of macroscopic, histologic and enzyme histochemical methods the concept of Schuhmann and Wehler (1971) that the mature human placenta shows a morphological organization coincides with bloodflow-units was examined. The investigation deals with the existence and distribution of terminal villi which can be distinguished on the basis of histological and enzyme histochemical peculiarities. 90 placentas were available, 3 of which were premature. In 6 cases one half of the placenta or the whole organ was cut into serial sections. Mature placentas. Per dissected placenta on an average 6--7 regions with cavities in the intervillous space could be observed, which might correlate to the \"placentones\" postulated by Schuhmann and Wehler (1971). Using histological techniques at random scattered areas of different size of so-called \"immature\" villi exist in the near of the basal plate; a relation between these areas and the placentones cannot be seen. All enzymes investigated possess a lower activity in the syncytiotrophoblast of the immature villi than in the mature ones. The demonstration of phosphatases and lysosomal enzymes reveals groups of mature villi with increased activity; they form a patchy enzyme pattern. With the exception of dehydrogenases there is no relation between villi with special enzyme activities and the placentones. Premature placentas. The younger the placenta, the larger is the volume of immature villi. Result. At present a organization of the human placenta into morphological units which correlates to the bloodflow (placentones) cannot be seen. A principle of segmentation which bases on differences between the terminal villi cannot be demonstrated.", "contents": "[On the organization of the mature human placenta (author's transl)]. By means of macroscopic, histologic and enzyme histochemical methods the concept of Schuhmann and Wehler (1971) that the mature human placenta shows a morphological organization coincides with bloodflow-units was examined. The investigation deals with the existence and distribution of terminal villi which can be distinguished on the basis of histological and enzyme histochemical peculiarities. 90 placentas were available, 3 of which were premature. In 6 cases one half of the placenta or the whole organ was cut into serial sections. Mature placentas. Per dissected placenta on an average 6--7 regions with cavities in the intervillous space could be observed, which might correlate to the \"placentones\" postulated by Schuhmann and Wehler (1971). Using histological techniques at random scattered areas of different size of so-called \"immature\" villi exist in the near of the basal plate; a relation between these areas and the placentones cannot be seen. All enzymes investigated possess a lower activity in the syncytiotrophoblast of the immature villi than in the mature ones. The demonstration of phosphatases and lysosomal enzymes reveals groups of mature villi with increased activity; they form a patchy enzyme pattern. With the exception of dehydrogenases there is no relation between villi with special enzyme activities and the placentones. Premature placentas. The younger the placenta, the larger is the volume of immature villi. Result. At present a organization of the human placenta into morphological units which correlates to the bloodflow (placentones) cannot be seen. A principle of segmentation which bases on differences between the terminal villi cannot be demonstrated."}
{"id": "PMID:199132", "title": "Stimulated neutrophil locomotion: chemokinesis and chemotaxis.", "content": "All leukocytes are capable of responding chemotactically (oriented locomotion) and chemokinetically (stimulated nondirected or random locomotion) to a variety of chemical agents. A brief review of the in vitro and in vivo methods of studying neutrophil movement and our present knowledge of chemotactic factors is presented as well as a discussion on the mechanisms of stimulated movement. Two clinically important instances of defects in neutrophil movement, ie, the Ch\u00e9diak-Higashi syndrome and a case of actin dysfunction, are herein described.", "contents": "Stimulated neutrophil locomotion: chemokinesis and chemotaxis. All leukocytes are capable of responding chemotactically (oriented locomotion) and chemokinetically (stimulated nondirected or random locomotion) to a variety of chemical agents. A brief review of the in vitro and in vivo methods of studying neutrophil movement and our present knowledge of chemotactic factors is presented as well as a discussion on the mechanisms of stimulated movement. Two clinically important instances of defects in neutrophil movement, ie, the Ch\u00e9diak-Higashi syndrome and a case of actin dysfunction, are herein described."}
{"id": "PMID:199133", "title": "Clinical, histopathological, and biochemical findings in Fabry's disease. A case report and family study.", "content": "An extensive enzymatic and morphological study was performed in a 38-year-old patient with Fabry's disease (FD). The quantitative evaluation of the enzyme alpha-galactosidase was shown to be important in identifying the genetic distribution of FD in the family tree of the patient under study. An enzymatic activity less than 0.5 nanomole/hr/10(6) cells and ranging from 2.2 to 1.1 nanomoles/hr/10(6) cells was found in the affected males and the heterozygous females, respectively. alpha-galactosidase activity in the patient's leukocytes correlates well with the histopathological findings of the kidney and skin biopsy specimens, thus demonstrating the need for both of these special examinations for a correct diagnosis of FD.", "contents": "Clinical, histopathological, and biochemical findings in Fabry's disease. A case report and family study. An extensive enzymatic and morphological study was performed in a 38-year-old patient with Fabry's disease (FD). The quantitative evaluation of the enzyme alpha-galactosidase was shown to be important in identifying the genetic distribution of FD in the family tree of the patient under study. An enzymatic activity less than 0.5 nanomole/hr/10(6) cells and ranging from 2.2 to 1.1 nanomoles/hr/10(6) cells was found in the affected males and the heterozygous females, respectively. alpha-galactosidase activity in the patient's leukocytes correlates well with the histopathological findings of the kidney and skin biopsy specimens, thus demonstrating the need for both of these special examinations for a correct diagnosis of FD."}
{"id": "PMID:199134", "title": "Adenomyoma: a precursor of extrauterine M\u00fcllerian adenosarcoma?", "content": "One patient had an extrauterine pelvic M\u00fcllerian adenosarcoma that recurred on multiple occasions and was originally diagnosed as a benign lesion. Caution is needed in the initial interpretatrion of such lesions as \"adenofibromas.\" We have compared this lesion with a benign adenomyoma of the uterus from a second patient and suggest that such benign neoplasms serve as precursors for M\u00fcllerian adenosarcoma in some cases. Light and electron microscopic observations in the first case as well as data from the literature support this hypothesis.", "contents": "Adenomyoma: a precursor of extrauterine M\u00fcllerian adenosarcoma? One patient had an extrauterine pelvic M\u00fcllerian adenosarcoma that recurred on multiple occasions and was originally diagnosed as a benign lesion. Caution is needed in the initial interpretatrion of such lesions as \"adenofibromas.\" We have compared this lesion with a benign adenomyoma of the uterus from a second patient and suggest that such benign neoplasms serve as precursors for M\u00fcllerian adenosarcoma in some cases. Light and electron microscopic observations in the first case as well as data from the literature support this hypothesis."}
{"id": "PMID:199135", "title": "Acidophil stem cell adenoma of the human pituitary.", "content": "Among 87 pituitary adenomas, four neoplasms had a superficial resemblance to undifferentiated cell adenomas and some fine structural features of both sparsely granulated adenomatous growth hormone and prolactin cells. Misplaced exocytosis, fibrous bodies, and multiple centrioles were sometimes revealed within the same cell and usually were accompanied by oncocytic transformation, mitochondrial alterations, and abnormal centriologenesis. The patients had normal or low blood growth hormone levels and elevated or normal prolactin values. All the tumors that were tested contained immunoreactive growth hormone and prolactin, irrespective of the blood hormone levels. The four tumors could represent a hitherto unclassified adenoma type and derive from the common, committed precursor of the two acidophils. The term acidophil stem cell adenoma is proposed to designate this entity.", "contents": "Acidophil stem cell adenoma of the human pituitary. Among 87 pituitary adenomas, four neoplasms had a superficial resemblance to undifferentiated cell adenomas and some fine structural features of both sparsely granulated adenomatous growth hormone and prolactin cells. Misplaced exocytosis, fibrous bodies, and multiple centrioles were sometimes revealed within the same cell and usually were accompanied by oncocytic transformation, mitochondrial alterations, and abnormal centriologenesis. The patients had normal or low blood growth hormone levels and elevated or normal prolactin values. All the tumors that were tested contained immunoreactive growth hormone and prolactin, irrespective of the blood hormone levels. The four tumors could represent a hitherto unclassified adenoma type and derive from the common, committed precursor of the two acidophils. The term acidophil stem cell adenoma is proposed to designate this entity."}
{"id": "PMID:199136", "title": "Multiple tumors after androgen therapy.", "content": "A case of multiple small well-differentiated hepatomas with early peliosis hepatis, multiple pancreatic islet cell tumors, and a renal medullary interstitial cell tumor following five years of androgen and prednisone therapy for idiopathic aplastic anemia is reported in a patient who died shortly after allogeneic bone marrow transplantation. The hepatic tumors were well differentiated, and the pancreatic tumors were of mixed ribbon and islet cell pattern. Therapeutic and experimental implications and the relevant literature are briefly summarized.", "contents": "Multiple tumors after androgen therapy. A case of multiple small well-differentiated hepatomas with early peliosis hepatis, multiple pancreatic islet cell tumors, and a renal medullary interstitial cell tumor following five years of androgen and prednisone therapy for idiopathic aplastic anemia is reported in a patient who died shortly after allogeneic bone marrow transplantation. The hepatic tumors were well differentiated, and the pancreatic tumors were of mixed ribbon and islet cell pattern. Therapeutic and experimental implications and the relevant literature are briefly summarized."}
{"id": "PMID:199138", "title": "Dominant lethal mutations in male mice.", "content": "Dominant lethal mutations are due to chromosome aberrations as demonstrated by analysis of first cleavage. With a sample size of 40-45 mice per dose the induction of dominant lethal mutations by 10 mg/kg of methyl methanesulfonat (MMS) can be detected in spermatids in the mating interval 9-12 days posttreatment (6-11%). In the same mating interval a dose of 150 mg/kg of MMS induces 100% dominant lethal mutations. MMS and other chemical mutagens can be characterized by their different spermatogenic response. The germ cell stage specific induction of dominant lethal mutations by chemical agents is very likely due to their different pathways and therefore, to different effects on the structural and macromolecular changes during spermatogenesis. The feasibility of standardizing test protocol for the dominant lethal assay in mice, based on collaborative studies, is discussed. The reproducibility of results and the sensitivity of the induction of dominant lethal mutations in the collaborative studies demonstrate the usefullness of the method for mutagenicity screening.", "contents": "Dominant lethal mutations in male mice. Dominant lethal mutations are due to chromosome aberrations as demonstrated by analysis of first cleavage. With a sample size of 40-45 mice per dose the induction of dominant lethal mutations by 10 mg/kg of methyl methanesulfonat (MMS) can be detected in spermatids in the mating interval 9-12 days posttreatment (6-11%). In the same mating interval a dose of 150 mg/kg of MMS induces 100% dominant lethal mutations. MMS and other chemical mutagens can be characterized by their different spermatogenic response. The germ cell stage specific induction of dominant lethal mutations by chemical agents is very likely due to their different pathways and therefore, to different effects on the structural and macromolecular changes during spermatogenesis. The feasibility of standardizing test protocol for the dominant lethal assay in mice, based on collaborative studies, is discussed. The reproducibility of results and the sensitivity of the induction of dominant lethal mutations in the collaborative studies demonstrate the usefullness of the method for mutagenicity screening."}
{"id": "PMID:199139", "title": "The role of mammals in the future of chemical mutagenesis research.", "content": "Radiation genetics has demonstrated that mutagenesis is a complex process affected by many factors. The ABCW hypothesis, that mutation frequency per rad over a wide range of organisms, from microbes to man, is linearly related to DNA content, ignores the fact that, within the mouse alone, different cell stages exhibit a range of mutation rates greater than that listed for the whole evolutionary tree. Also ignored are the findings that the important effects of dose rate and some other factors in the mouse were not predictable even from Drosophila. A much greater maze of complexities has already been found in chemical mutagenesis. This is illustrated even by the results obtained from testing of a single drug. Thus, it is clear that the attempt to extend the ABCW hypothesis to chemicals will be of little, if any, predictive value. Similarly, such concepts as the REC (roentgen-equivalent-chemical), designed to express the mutagenic risk from a chemical by a single unit quantitatively related to radiation damage, are defeated by the extreme qualitative differences in response. Unifying theories and simple non-mammalian tests that reliably predict the results in mammals cannot be expected to materialize until much more information has been collected on transmitted mutations induced in mammalian germ cells.", "contents": "The role of mammals in the future of chemical mutagenesis research. Radiation genetics has demonstrated that mutagenesis is a complex process affected by many factors. The ABCW hypothesis, that mutation frequency per rad over a wide range of organisms, from microbes to man, is linearly related to DNA content, ignores the fact that, within the mouse alone, different cell stages exhibit a range of mutation rates greater than that listed for the whole evolutionary tree. Also ignored are the findings that the important effects of dose rate and some other factors in the mouse were not predictable even from Drosophila. A much greater maze of complexities has already been found in chemical mutagenesis. This is illustrated even by the results obtained from testing of a single drug. Thus, it is clear that the attempt to extend the ABCW hypothesis to chemicals will be of little, if any, predictive value. Similarly, such concepts as the REC (roentgen-equivalent-chemical), designed to express the mutagenic risk from a chemical by a single unit quantitatively related to radiation damage, are defeated by the extreme qualitative differences in response. Unifying theories and simple non-mammalian tests that reliably predict the results in mammals cannot be expected to materialize until much more information has been collected on transmitted mutations induced in mammalian germ cells."}
{"id": "PMID:199141", "title": "Cell receptors for paramyxoviruses.", "content": "Treatment of chick embryo fibroblasts, calf kidney and BHK cells for 30 minutes with the enzyme neuraminidase from Vibrio cholerae causes an enhancement of the per cent of attached NDV virions. This enhancement does not depend on the multiplicity of infection. The quantity of spontaneously eluted and cellbound virus is two times greater than the quantity of the same virus derived from control cells. N-acetyl-neuramin lactose inhibits the effect of Vibrio cholerae neuraminidase. After prolonged action of this enzyme, the quantity of adsorbed NDV diminishes. Treatment of the same cells with neuraminidase from influenza virus decreases the per cent of adsorbed NDV with respect to controls. The other paramyxovirus--bovine parainfluenza 3 virus adsorbs also more intensively on cells treated with Vibrio cholerae neuraminidase. It is suggested that partial hydrolysis of NANA molecules causes a rearrangement of the cell surface charged groups and thus allows a more effective contact between paramyxoviruses and the cell.", "contents": "Cell receptors for paramyxoviruses. Treatment of chick embryo fibroblasts, calf kidney and BHK cells for 30 minutes with the enzyme neuraminidase from Vibrio cholerae causes an enhancement of the per cent of attached NDV virions. This enhancement does not depend on the multiplicity of infection. The quantity of spontaneously eluted and cellbound virus is two times greater than the quantity of the same virus derived from control cells. N-acetyl-neuramin lactose inhibits the effect of Vibrio cholerae neuraminidase. After prolonged action of this enzyme, the quantity of adsorbed NDV diminishes. Treatment of the same cells with neuraminidase from influenza virus decreases the per cent of adsorbed NDV with respect to controls. The other paramyxovirus--bovine parainfluenza 3 virus adsorbs also more intensively on cells treated with Vibrio cholerae neuraminidase. It is suggested that partial hydrolysis of NANA molecules causes a rearrangement of the cell surface charged groups and thus allows a more effective contact between paramyxoviruses and the cell."}
{"id": "PMID:199142", "title": "The effect of ultraviolet light on primary herpes simplex virus infection in the mouse.", "content": "The effect of irradiation with UV light on herpes simplex virus infection in the mouse ear was investigated. Irradiation 2 days before infection had no effect on the titre of virus in the skin 3 days after infection. In ears irradiated 24 hours or immediately before infection virus titres measured 3 days after infection were depressed. Irradiation 2 days after infection enhanced virus titres. The dose of irradiation used did not directly inactivate herpes simplex virus in the ear. The results are discussed with reference to theories of herpes simplex reactivation.", "contents": "The effect of ultraviolet light on primary herpes simplex virus infection in the mouse. The effect of irradiation with UV light on herpes simplex virus infection in the mouse ear was investigated. Irradiation 2 days before infection had no effect on the titre of virus in the skin 3 days after infection. In ears irradiated 24 hours or immediately before infection virus titres measured 3 days after infection were depressed. Irradiation 2 days after infection enhanced virus titres. The dose of irradiation used did not directly inactivate herpes simplex virus in the ear. The results are discussed with reference to theories of herpes simplex reactivation."}
{"id": "PMID:199143", "title": "[Immunohistochemical characteristics of cells of the adenohypophysis producing adrenocorticotropic hormone].", "content": "By means of immune fluorescence and histochemical methods, adenohypophyseal corticotropocytes from intact rats and the rats subjected to immobilization stress were studied. The data obtained demonstrated that according to their tinctorial properties, corticotropocytes are chromophobic adenocytes and some of them contain small aldehyde-fuchsinophil and PAS-positives granules. After an acute stress, corticotropocytes secrete ACTH into the intracellular space, and the cytoplasmic processes secrete it into the pericapillar space. Under a prolonged stress, the latter phenomenon prevails.", "contents": "[Immunohistochemical characteristics of cells of the adenohypophysis producing adrenocorticotropic hormone]. By means of immune fluorescence and histochemical methods, adenohypophyseal corticotropocytes from intact rats and the rats subjected to immobilization stress were studied. The data obtained demonstrated that according to their tinctorial properties, corticotropocytes are chromophobic adenocytes and some of them contain small aldehyde-fuchsinophil and PAS-positives granules. After an acute stress, corticotropocytes secrete ACTH into the intracellular space, and the cytoplasmic processes secrete it into the pericapillar space. Under a prolonged stress, the latter phenomenon prevails."}
{"id": "PMID:199144", "title": "[Malignant glomus tumor of the jejunum with distant metastases].", "content": "An autopsy observation of a malignant glomal tumor (angioleiomyomatotic variant) of rare localization (jejunum) with degeneration, outgrowth through the intestinal wall, and numerous metastases (regional, paratracheal and bifurcational lymph nodes, the liver, lungs) in a man of 65 is described.", "contents": "[Malignant glomus tumor of the jejunum with distant metastases]. An autopsy observation of a malignant glomal tumor (angioleiomyomatotic variant) of rare localization (jejunum) with degeneration, outgrowth through the intestinal wall, and numerous metastases (regional, paratracheal and bifurcational lymph nodes, the liver, lungs) in a man of 65 is described."}
{"id": "PMID:199145", "title": "Alternating proptosis. A case report of acute orbital myositis defined by the computerized tomographic scan.", "content": "A 27-year-old woman had a two-week course of acute painful right proptosis with ptosis, medial conjunctival injection, and restriction of eye movements--particularly abduction. One month later, a similar remitting painful left proptosis with complete limitation of abduction developed. Computerized tomographic x-ray scanning showed marked contrast enhancement of both medial rectus muscles, documenting the presumptive diagnosis of acute orbital myositis without recourse to invasive diagnostic techniques. Myositis is a common component of idiopathic orbital inflammatory disease (orbital pseudotumor), but awareness of the rare patient with acute inflammation clinically localized to the extraocular muscles will decrease confusion with cranial nerve and cavernous sinus disease.", "contents": "Alternating proptosis. A case report of acute orbital myositis defined by the computerized tomographic scan. A 27-year-old woman had a two-week course of acute painful right proptosis with ptosis, medial conjunctival injection, and restriction of eye movements--particularly abduction. One month later, a similar remitting painful left proptosis with complete limitation of abduction developed. Computerized tomographic x-ray scanning showed marked contrast enhancement of both medial rectus muscles, documenting the presumptive diagnosis of acute orbital myositis without recourse to invasive diagnostic techniques. Myositis is a common component of idiopathic orbital inflammatory disease (orbital pseudotumor), but awareness of the rare patient with acute inflammation clinically localized to the extraocular muscles will decrease confusion with cranial nerve and cavernous sinus disease."}
{"id": "PMID:199146", "title": "Dapsone-induced peripheral neuropathy.", "content": "Peripheral neuropathy is a rare complication of dapsone therapy. This neuropathy appears primarily to be of the motor type, and recovery occurs on discontinuation of the drug therapy. The patient in  this report developed a marked motor deficit as well as a selective marked loss of vibration sense shortly after the initiation of a relatively low dose of dapsone. Recovery was rapid on cessation of the therapy. This patient was found to be a slow acetylator of isoniazid, and therefore is probably a slow acetylator of dapsone. The possible mechanisms of the neurotoxicity of dapsone and the role of altered metabolism are discussed.", "contents": "Dapsone-induced peripheral neuropathy. Peripheral neuropathy is a rare complication of dapsone therapy. This neuropathy appears primarily to be of the motor type, and recovery occurs on discontinuation of the drug therapy. The patient in  this report developed a marked motor deficit as well as a selective marked loss of vibration sense shortly after the initiation of a relatively low dose of dapsone. Recovery was rapid on cessation of the therapy. This patient was found to be a slow acetylator of isoniazid, and therefore is probably a slow acetylator of dapsone. The possible mechanisms of the neurotoxicity of dapsone and the role of altered metabolism are discussed."}
{"id": "PMID:199147", "title": "Endocrine influences on ulceration and regeneration in the alkali-burned cornea.", "content": "Subconjunctival dibutyryl 3',5' cyclic adenosine monophosphoric acid (DBcAMP) produced a statistically significant reduction of ulceration in the alkaliburned rabbit cornea. No effect on epithelial cell growth was observed. DBcAMP also caused a statistically significant acceleration of corneal neovascularization in the first two weeks postburn. Medroxyprogesterone acetate also affected the development  of corneal ulcers postalkali burn, but in a less well-defined manner. Dinoprost and indomethacin did not seem to influence this lesion. Cyclic adenosine monophosphoric acid may therefore possess a potential for use in the alkali-burned human eye.", "contents": "Endocrine influences on ulceration and regeneration in the alkali-burned cornea. Subconjunctival dibutyryl 3',5' cyclic adenosine monophosphoric acid (DBcAMP) produced a statistically significant reduction of ulceration in the alkaliburned rabbit cornea. No effect on epithelial cell growth was observed. DBcAMP also caused a statistically significant acceleration of corneal neovascularization in the first two weeks postburn. Medroxyprogesterone acetate also affected the development  of corneal ulcers postalkali burn, but in a less well-defined manner. Dinoprost and indomethacin did not seem to influence this lesion. Cyclic adenosine monophosphoric acid may therefore possess a potential for use in the alkali-burned human eye."}
{"id": "PMID:199148", "title": "Treatment of hypercholesterolaemia with oral lecithin.", "content": "An open clinical trial was performed to evaluate the plasma cholesterol-lowering potential of oral lecithin in large doses (20--30 g/day), with or without supplementary clofibrate. Three healthy subjects and seven patients with hypercholesterolaemia were studied over periods ranging from eight weeks to 11 months. In one-third of healthy subjects and in 3/7 patients, lecithin therapy led to a significant fall in plasma cholesterol concentration (10--18% fall). Combination of lecithin and clofibrate in two of the patients led to still lower plasma cholesterol levels (21 and 22% fall). Most of the change in plasma cholesterol concentration, when it occurred, was due to a reduction in beta lipoproteins. Evidence is presented that oral lecithin may reduce plasma cholesterol levels by acting as a source of linoleic acid.", "contents": "Treatment of hypercholesterolaemia with oral lecithin. An open clinical trial was performed to evaluate the plasma cholesterol-lowering potential of oral lecithin in large doses (20--30 g/day), with or without supplementary clofibrate. Three healthy subjects and seven patients with hypercholesterolaemia were studied over periods ranging from eight weeks to 11 months. In one-third of healthy subjects and in 3/7 patients, lecithin therapy led to a significant fall in plasma cholesterol concentration (10--18% fall). Combination of lecithin and clofibrate in two of the patients led to still lower plasma cholesterol levels (21 and 22% fall). Most of the change in plasma cholesterol concentration, when it occurred, was due to a reduction in beta lipoproteins. Evidence is presented that oral lecithin may reduce plasma cholesterol levels by acting as a source of linoleic acid."}
{"id": "PMID:199151", "title": "Lymphoid leukosis: interrelations among virus infections in hens, eggs, embryos, and chicks.", "content": "Hens from a commercial source were selected because they were infected with lymphoid leukosis virus (LLV). LLV was detected in vaginal swabs from 17 viremic hens and from 27 of 44 hens that were not viremic. All hens that were positive on the vaginal swab test (VST) produced one or more eggs with virus in albumen or in embryos, whereas in comparable tests, virus was detected only in eggs from 5 of 17 hens that were negative on VST. Congenital transmission of LLV was erratic and neither the VST nor tests for virus in egg albumen prior to incubating eggs identified all hens that transmitted infection. For example, 14 hens negative on VST produced 50 eggs negative for virus in albumen and yet one of the embryos from these eggs was infected. Eggs from other hens had infectious virus in albumen and about half of the embryos from these were infected. Tests for virus in cloacal swabs from one-day-old chicks were as sensitive as tests on embryos for detecting congenital transmission. Titers of LLV in the meconium of congenitally infected chicks were as high as 10(7) infectious units per ml. The cloacal swab test should be a valuable adjunct to the VST and tests on egg albumen in programs designed to eradicate lymphoid leukosis from chickens.", "contents": "Lymphoid leukosis: interrelations among virus infections in hens, eggs, embryos, and chicks. Hens from a commercial source were selected because they were infected with lymphoid leukosis virus (LLV). LLV was detected in vaginal swabs from 17 viremic hens and from 27 of 44 hens that were not viremic. All hens that were positive on the vaginal swab test (VST) produced one or more eggs with virus in albumen or in embryos, whereas in comparable tests, virus was detected only in eggs from 5 of 17 hens that were negative on VST. Congenital transmission of LLV was erratic and neither the VST nor tests for virus in egg albumen prior to incubating eggs identified all hens that transmitted infection. For example, 14 hens negative on VST produced 50 eggs negative for virus in albumen and yet one of the embryos from these eggs was infected. Eggs from other hens had infectious virus in albumen and about half of the embryos from these were infected. Tests for virus in cloacal swabs from one-day-old chicks were as sensitive as tests on embryos for detecting congenital transmission. Titers of LLV in the meconium of congenitally infected chicks were as high as 10(7) infectious units per ml. The cloacal swab test should be a valuable adjunct to the VST and tests on egg albumen in programs designed to eradicate lymphoid leukosis from chickens."}
{"id": "PMID:199152", "title": "Pathogenicity of low-virulence Marek's disease viruses in normal versus immunologically compromised chickens.", "content": "To learn whether \"low virulence\" isolants of Marek's disease (MD) virus have a low inherent oncogenic potential, 3 isolants (CU-1, CU-2, S-11) were given to genetically susceptible S-strain or P-line birds with or without immunosuppressive treatments. Based on lesion incidence and type during an 8-10-week experimental period, embryonal (17-day) bursectomy and neonatal cyclophosphamide (CY) treatment were without effect on CU-1 and CU-2 infections in P-lines. S-11 virus was virulent for P-lines, and CY treatment reduced MD incidence as reported by others for virulent virus infections. Neonatal thymectomy or infection in ovo (at 8 days of incubation) or use of the more susceptible S-strain chicks all increased the incidence of MD induced by CU-1 and CU-2 viruses. It was concluded that the \"low virulence\" of these viruses is a reflection of an adequate immune response by the host.", "contents": "Pathogenicity of low-virulence Marek's disease viruses in normal versus immunologically compromised chickens. To learn whether \"low virulence\" isolants of Marek's disease (MD) virus have a low inherent oncogenic potential, 3 isolants (CU-1, CU-2, S-11) were given to genetically susceptible S-strain or P-line birds with or without immunosuppressive treatments. Based on lesion incidence and type during an 8-10-week experimental period, embryonal (17-day) bursectomy and neonatal cyclophosphamide (CY) treatment were without effect on CU-1 and CU-2 infections in P-lines. S-11 virus was virulent for P-lines, and CY treatment reduced MD incidence as reported by others for virulent virus infections. Neonatal thymectomy or infection in ovo (at 8 days of incubation) or use of the more susceptible S-strain chicks all increased the incidence of MD induced by CU-1 and CU-2 viruses. It was concluded that the \"low virulence\" of these viruses is a reflection of an adequate immune response by the host."}
{"id": "PMID:199153", "title": "Serological response of chickens exposed to a type 1 avian adenovirus alone or in combination with the adeno-associated virus.", "content": "The avian adenoviruses (AV) are common infectious agents of poultry and other avian species throughout the world (1,4,8). Limited observations suggest that the adeno-associated virus (A-AV) coinfects many of the chickens that carry AV (8). The presence and persistence of these infections in a flock is often determined by serological methods. In the current study, the immune response of chickens to type 1 AV alone and to a dual exposure, AV plus A-AV, was followed over a 12-week period with a variety of serological tests. The study also determined the duration of the viral infections.", "contents": "Serological response of chickens exposed to a type 1 avian adenovirus alone or in combination with the adeno-associated virus. The avian adenoviruses (AV) are common infectious agents of poultry and other avian species throughout the world (1,4,8). Limited observations suggest that the adeno-associated virus (A-AV) coinfects many of the chickens that carry AV (8). The presence and persistence of these infections in a flock is often determined by serological methods. In the current study, the immune response of chickens to type 1 AV alone and to a dual exposure, AV plus A-AV, was followed over a 12-week period with a variety of serological tests. The study also determined the duration of the viral infections."}
{"id": "PMID:199157", "title": "Subcellular distribution of superoxide dismutases in human neutrophils. Influence of myeloperoxidase on the measurement of superoxide dismutase activity.", "content": "We have identified two distinct pools of superoxide dismutase in fractions of human peripheral neutrophils obtained by the isopycnic fractionation of homogenates of the latter with linear sucrose gradients. Superoxide dismutase activity, observed with polyacrylamide gels impregnated with Nitro Blue Tetrazolium, was present in: (1) the mitochondrial fraction [density (rho) 1.169g/ml], containing the high-molecular-weight KCN-resistant enzyme, and (2) the cytoplasm fraction, containing the low-molecular-weight KCN-sensitive enzyme. Superoxide dismutase activity, observed with a quantitative assay involving cytochrome c, was present in: (1) the mitochondria, (2) the cytoplasm, and (3) the azurophil-granule fractions (rho=1.206 and 1.222g/ml). No substantial enzyme activity was observed in specific-granule fractions (rho=1.187g/ml) or in the membranous fraction (rho=1.136g/ml) in either assay. The apparent superoxide dismutase activity observed in the azurophil granules with the cytochrome c assay was attributable not to true superoxide dismutase but to myeloperoxidase, an enzyme found solely in the azurophil granules. In the presence of H(2)O(2), human neutrophil myeloperoxidase oxidized ferrocytochrome c. Thus, in the cytochrome c assay for superoxide dismutase, the oxidation of ferrocytochrome c by myeloperoxidase mimicked the inhibition of reduction of ferricytochrome c by superoxide dismutase. When myeloperoxidase was removed from azurophilgranule fractions by specific immuno-affinity chromatography, both myeloperoxidase and apparent superoxide dismutase activities were removed. It is concluded that there is no detectable superoxide dismutase in either the azurophil or specific granules of human neutrophils. Mitochondrial superoxide dismutase, 15% of the total dismutase activity of the cells, occurred only in fractions of density 1.160g/ml, where isocitrate dehydrogenase and cytochrome oxidase were also observed.", "contents": "Subcellular distribution of superoxide dismutases in human neutrophils. Influence of myeloperoxidase on the measurement of superoxide dismutase activity. We have identified two distinct pools of superoxide dismutase in fractions of human peripheral neutrophils obtained by the isopycnic fractionation of homogenates of the latter with linear sucrose gradients. Superoxide dismutase activity, observed with polyacrylamide gels impregnated with Nitro Blue Tetrazolium, was present in: (1) the mitochondrial fraction [density (rho) 1.169g/ml], containing the high-molecular-weight KCN-resistant enzyme, and (2) the cytoplasm fraction, containing the low-molecular-weight KCN-sensitive enzyme. Superoxide dismutase activity, observed with a quantitative assay involving cytochrome c, was present in: (1) the mitochondria, (2) the cytoplasm, and (3) the azurophil-granule fractions (rho=1.206 and 1.222g/ml). No substantial enzyme activity was observed in specific-granule fractions (rho=1.187g/ml) or in the membranous fraction (rho=1.136g/ml) in either assay. The apparent superoxide dismutase activity observed in the azurophil granules with the cytochrome c assay was attributable not to true superoxide dismutase but to myeloperoxidase, an enzyme found solely in the azurophil granules. In the presence of H(2)O(2), human neutrophil myeloperoxidase oxidized ferrocytochrome c. Thus, in the cytochrome c assay for superoxide dismutase, the oxidation of ferrocytochrome c by myeloperoxidase mimicked the inhibition of reduction of ferricytochrome c by superoxide dismutase. When myeloperoxidase was removed from azurophilgranule fractions by specific immuno-affinity chromatography, both myeloperoxidase and apparent superoxide dismutase activities were removed. It is concluded that there is no detectable superoxide dismutase in either the azurophil or specific granules of human neutrophils. Mitochondrial superoxide dismutase, 15% of the total dismutase activity of the cells, occurred only in fractions of density 1.160g/ml, where isocitrate dehydrogenase and cytochrome oxidase were also observed."}
{"id": "PMID:199158", "title": "Collagen synthesis in the muscle of developing chick embryos.", "content": "Radioactive protein was prepared from the leg muscle of chick embryos, 11, 14, 16 and 17 days old, each injected with radioactive proline and incubated for 30, 60 or 90 min afterwards. The radioactive protein was incubated with collagenase purified by chromatography on a Sephadex G-100 column. Under this condition, only collagen is digested into products soluble in trichloroacetic acid. The relative rate of collagen synthesis was determined by comparing the amount of radioactivity released into the supernatant fraction and that in the residue, by the method of Diegelmann & Peterkofsky [(1972) Dev. Biol. 28, 443--453]. The results show that the rate of collagen synthesis remains at approx. 10% of the rate of synthesis of other non-collagenous proteins during the development of chick embryonic muscle from 11 to 17 days. This suggests that the synthesis of collagen and that of other proteins are co-ordinately regulated at these stages of development.", "contents": "Collagen synthesis in the muscle of developing chick embryos. Radioactive protein was prepared from the leg muscle of chick embryos, 11, 14, 16 and 17 days old, each injected with radioactive proline and incubated for 30, 60 or 90 min afterwards. The radioactive protein was incubated with collagenase purified by chromatography on a Sephadex G-100 column. Under this condition, only collagen is digested into products soluble in trichloroacetic acid. The relative rate of collagen synthesis was determined by comparing the amount of radioactivity released into the supernatant fraction and that in the residue, by the method of Diegelmann & Peterkofsky [(1972) Dev. Biol. 28, 443--453]. The results show that the rate of collagen synthesis remains at approx. 10% of the rate of synthesis of other non-collagenous proteins during the development of chick embryonic muscle from 11 to 17 days. This suggests that the synthesis of collagen and that of other proteins are co-ordinately regulated at these stages of development."}
{"id": "PMID:199159", "title": "Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate.", "content": "1. The subcellular distribution of adenine nucleotides, acetyl-CoA, CoA, glutamate, 2-oxoglutarate, malate, oxaloacetate, pyruvate, phosphoenolpyruvate, 3-phosphoglycerate, glucose 6-phosphate, aspartate and citrate was studied in isolated hepatocytes in the absence and presence of glucagon by using a modified digitonin procedure for cell fractionation. 2. In the absence of glucagon, the cytosol contains about two-thirds of cellular ATP, some 40-50% of ADP, acetyl-CoA, citrate and phosphoenolpyruvate, more than 75% of total 2-oxoglutarate, glutamate, malate, oxaloacetate, pyruvate, 3-phosphoglycerate and aspartate, and all of glucose 6-phosphate. 3. In the presence of glucagon the cytosolic space shows an increase in the content of malate, phosphoenolpyruvate and 3-phosphoglycerate by more than 60%, and those of aspartate and glucose 6-phosphate rise by about 25%. Other metabolites remain unchanged. After glucagon treatment, cytosolic pyruvate is decreased by 37%, whereas glutamate and 2-oxoglutarate decrease by 70%. The [NAD(+)]/[NADH] ratios calculated from the cytosolic concentrations of the reactants of lactate dehydrogenase and malate dehydrogenase were the same. Glucagon shifts this ratio and also that of the [NADP(+)]/[NADPH] couple towards a more reduced state. 4. In the mitochondrial space glucagon causes an increase in the acetyl-CoA and ATP contents by 25%, and an increase in [phosphoenolpyruvate] by 50%. Other metabolites are not changed by glucagon. Oxaloacetate in the matrix is only slightly decreased after glucagon, yet glutamate and 2-oxoglutarate fall to about 25% of the respective control values. The [NAD(+)]/[NADH] ratios as calculated from the [3-hydroxybutyrate]/[acetoacetate] ratio and from the matrix [malate]/[oxaloacetate] couple are lowered by glucagon, yet in the latter case the values are about tenfold higher than in the former. 5. Glucagon and oleate stimulate gluconeogenesis from lactate to nearly the same extent. Oleate, however, does not produce the changes in cellular 2-oxoglutarate and glutamate as observed with glucagon. 6. The changes of the subcellular metabolite distribution after glucagon are compatible with the proposal that the stimulation of gluconeogenesis results from as yet unknown action(s) of the hormone at the mitochondrial level in concert with its established effects on proteolysis and lipolysis.", "contents": "Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. 1. The subcellular distribution of adenine nucleotides, acetyl-CoA, CoA, glutamate, 2-oxoglutarate, malate, oxaloacetate, pyruvate, phosphoenolpyruvate, 3-phosphoglycerate, glucose 6-phosphate, aspartate and citrate was studied in isolated hepatocytes in the absence and presence of glucagon by using a modified digitonin procedure for cell fractionation. 2. In the absence of glucagon, the cytosol contains about two-thirds of cellular ATP, some 40-50% of ADP, acetyl-CoA, citrate and phosphoenolpyruvate, more than 75% of total 2-oxoglutarate, glutamate, malate, oxaloacetate, pyruvate, 3-phosphoglycerate and aspartate, and all of glucose 6-phosphate. 3. In the presence of glucagon the cytosolic space shows an increase in the content of malate, phosphoenolpyruvate and 3-phosphoglycerate by more than 60%, and those of aspartate and glucose 6-phosphate rise by about 25%. Other metabolites remain unchanged. After glucagon treatment, cytosolic pyruvate is decreased by 37%, whereas glutamate and 2-oxoglutarate decrease by 70%. The [NAD(+)]/[NADH] ratios calculated from the cytosolic concentrations of the reactants of lactate dehydrogenase and malate dehydrogenase were the same. Glucagon shifts this ratio and also that of the [NADP(+)]/[NADPH] couple towards a more reduced state. 4. In the mitochondrial space glucagon causes an increase in the acetyl-CoA and ATP contents by 25%, and an increase in [phosphoenolpyruvate] by 50%. Other metabolites are not changed by glucagon. Oxaloacetate in the matrix is only slightly decreased after glucagon, yet glutamate and 2-oxoglutarate fall to about 25% of the respective control values. The [NAD(+)]/[NADH] ratios as calculated from the [3-hydroxybutyrate]/[acetoacetate] ratio and from the matrix [malate]/[oxaloacetate] couple are lowered by glucagon, yet in the latter case the values are about tenfold higher than in the former. 5. Glucagon and oleate stimulate gluconeogenesis from lactate to nearly the same extent. Oleate, however, does not produce the changes in cellular 2-oxoglutarate and glutamate as observed with glucagon. 6. The changes of the subcellular metabolite distribution after glucagon are compatible with the proposal that the stimulation of gluconeogenesis results from as yet unknown action(s) of the hormone at the mitochondrial level in concert with its established effects on proteolysis and lipolysis."}
{"id": "PMID:199160", "title": "Membrane cholesterol and cell fusion of hen and guinea-pig erythrocytes.", "content": "1. The cholesterol content of hen erythrocytes was modified by treating the cells with phospholipid liposomes. 2. Depletion of cellular cholesterol, by using liposomes of dipalmitoylglycerophosphocholine or phosphatidylcholine from hen erythrocytes, had no effect on the susceptibility of the cells to fusion induced by oleoylglycerol, but markedly decreased fusion induced by Sendai virus. 3. By contrast, enrichment of cellular cholesterol by using liposomes of dipalmitoylglycerophosphocholine and cholesterol increased cell fusion induced by oleoylglycerol, poly(ethylene glycol) and Sendai virus. 4. Virus-induced cell fusion of guinea-pig erythrocytes, which were enriched in cholesterol by feeding a cholesterol-rich diet to the animals, was also enhanced. 5. Hen erythrocytes that were treated with liposomes prepared from egg phosphatidylcholine contained increased quantities of phospholipid phosphorus and fused readily on incubation with retinol, independently of their cholesterol content. 6. It is suggested that cholesterol may enhance cell fusion by acting to facilitate a phase separation of protein-free areas of lipid bilayer, which subsequently provide the sites for cell fusion.", "contents": "Membrane cholesterol and cell fusion of hen and guinea-pig erythrocytes. 1. The cholesterol content of hen erythrocytes was modified by treating the cells with phospholipid liposomes. 2. Depletion of cellular cholesterol, by using liposomes of dipalmitoylglycerophosphocholine or phosphatidylcholine from hen erythrocytes, had no effect on the susceptibility of the cells to fusion induced by oleoylglycerol, but markedly decreased fusion induced by Sendai virus. 3. By contrast, enrichment of cellular cholesterol by using liposomes of dipalmitoylglycerophosphocholine and cholesterol increased cell fusion induced by oleoylglycerol, poly(ethylene glycol) and Sendai virus. 4. Virus-induced cell fusion of guinea-pig erythrocytes, which were enriched in cholesterol by feeding a cholesterol-rich diet to the animals, was also enhanced. 5. Hen erythrocytes that were treated with liposomes prepared from egg phosphatidylcholine contained increased quantities of phospholipid phosphorus and fused readily on incubation with retinol, independently of their cholesterol content. 6. It is suggested that cholesterol may enhance cell fusion by acting to facilitate a phase separation of protein-free areas of lipid bilayer, which subsequently provide the sites for cell fusion."}
{"id": "PMID:199200", "title": "[Studies on the mechanism of action of clonidine (author's transl)].", "content": "The effects of 3.7-120 microgram 2-(2,6-dichloro-anilino)-2-imidazoline (clonidine, Catapresan)/kg i.v. on the arterial blood pressure and the central nervous activities of sympathetic and phrenic nerves were studied in 42 anaesthetized cats which had been relaxed and artificially respirated. At the dosage 3.7-30 microgram/kg clonidine produced a moderate fall of blood pressure and a more distinct sympathetic inhibitory effect. At a dosage of 60-120 microgram/kg an increase of the hypotensive action was not observed whereas the central nervous inhibition increased with the dosage. The activity of the respiratory centre remained constant. The pressor effects as well as the sympathetic stimulation effects of nicotine, nicetamide or asphyxia were reduced by the treatment with clonidine. At a dosage of 3.7-30 microgram clonidine/kg, i.e. including the 6fold therapeutic dosage, the inhibition of the evoked sympathetic activity was, however, considerably weaker than the inhibition of the sympathetic activity at rest. Therefore clonidine at a therapeutic dosage probably causes an activation of the central part of the pressor-receptor reflexes and as a result a decrease of the central sympathetic activity and the moderate fall in blood pressure. At a higher dosage the absence of increasing hypotensive effect in spite of increasing sympathetic inhibition is probably caused by a stimulation of peripheral postsynaptic alpha-adrenoreceptors.", "contents": "[Studies on the mechanism of action of clonidine (author's transl)]. The effects of 3.7-120 microgram 2-(2,6-dichloro-anilino)-2-imidazoline (clonidine, Catapresan)/kg i.v. on the arterial blood pressure and the central nervous activities of sympathetic and phrenic nerves were studied in 42 anaesthetized cats which had been relaxed and artificially respirated. At the dosage 3.7-30 microgram/kg clonidine produced a moderate fall of blood pressure and a more distinct sympathetic inhibitory effect. At a dosage of 60-120 microgram/kg an increase of the hypotensive action was not observed whereas the central nervous inhibition increased with the dosage. The activity of the respiratory centre remained constant. The pressor effects as well as the sympathetic stimulation effects of nicotine, nicetamide or asphyxia were reduced by the treatment with clonidine. At a dosage of 3.7-30 microgram clonidine/kg, i.e. including the 6fold therapeutic dosage, the inhibition of the evoked sympathetic activity was, however, considerably weaker than the inhibition of the sympathetic activity at rest. Therefore clonidine at a therapeutic dosage probably causes an activation of the central part of the pressor-receptor reflexes and as a result a decrease of the central sympathetic activity and the moderate fall in blood pressure. At a higher dosage the absence of increasing hypotensive effect in spite of increasing sympathetic inhibition is probably caused by a stimulation of peripheral postsynaptic alpha-adrenoreceptors."}
{"id": "PMID:199202", "title": "Studies of plasma viscosity in primary hyperlipoproteinaemia.", "content": "Using an Ubbelohde capillary viscometer, viscosity was determined in the plasma of 39 patients with a primary hyperlipoproteinaemia (type IIa, n=13; type IV, n=12; type IIb, n=14), in isolated lipoprotein fractions as well as in sera which differed only in their lipoprotein concentration. Plasma viscosity of the patients with hyperlipoproteinaemia was compared to that of a normolipidaemic control group and correlated with the lipid fractions characteristic of the different hyperlipoproteinaemia types. Plasma viscosity in types IIa, IV and IIb was found to be significantly higher than in the control group. Of the different hyperlipoproteinaemia types, IIa exhibited the lowest and IIb the highest plasma viscosity levels. The elevation of plasma viscosity was correlated with the concentration of lipoproteins (lipid fractions). In viscosity measurements of sera which varied only in lipoprotein concentrations, a correlation between the increase of viscosity and lipoprotein concentration as well as a greater efficiency of VLDL fractions was observed, similar to the viscosity results from isolated lipoproteins.", "contents": "Studies of plasma viscosity in primary hyperlipoproteinaemia. Using an Ubbelohde capillary viscometer, viscosity was determined in the plasma of 39 patients with a primary hyperlipoproteinaemia (type IIa, n=13; type IV, n=12; type IIb, n=14), in isolated lipoprotein fractions as well as in sera which differed only in their lipoprotein concentration. Plasma viscosity of the patients with hyperlipoproteinaemia was compared to that of a normolipidaemic control group and correlated with the lipid fractions characteristic of the different hyperlipoproteinaemia types. Plasma viscosity in types IIa, IV and IIb was found to be significantly higher than in the control group. Of the different hyperlipoproteinaemia types, IIa exhibited the lowest and IIb the highest plasma viscosity levels. The elevation of plasma viscosity was correlated with the concentration of lipoproteins (lipid fractions). In viscosity measurements of sera which varied only in lipoprotein concentrations, a correlation between the increase of viscosity and lipoprotein concentration as well as a greater efficiency of VLDL fractions was observed, similar to the viscosity results from isolated lipoproteins."}
{"id": "PMID:199204", "title": "Elastin sub-fraction as binding site for lipids.", "content": "Elastin preparations were isolated from human thoracic aorta, from atherosclerotic and from grossly normal regions. A relatively mild procedure was used to avoid hot alkaline extraction and autoclaving. The elastase digest of the aortic elastin was chromatographed on a Sephadex G-100 column and separated into two fractions: A (larger molecular weight) and B (smaller molecular weight). The ratio of fraction A to total aortic elastin increased with age and the development of the atherosclerosis. Amino acid and sugar analyses showed that fraction A consistently contained more polar amino acids, hexose, hexosamine and L-fucose, and less sialic acid, in comparison with fraction B. Part of the elastin preparation was incubated with human low-density lipoprotein; a considerable amount of lipid, especially cholesterol, was transferred from the lipoprotein to the elastin. Estimation of protein and cholesterol in fractions A and B of the elastase hydrolyzate of incubated elastin showed that most of the cholesterol taken up by elastin had been in fraction A. The increased proportion of fraction A in aortic elastin derived from plaque areas appeared responsible for the marked lipid-binding capacity of plaque elastin.", "contents": "Elastin sub-fraction as binding site for lipids. Elastin preparations were isolated from human thoracic aorta, from atherosclerotic and from grossly normal regions. A relatively mild procedure was used to avoid hot alkaline extraction and autoclaving. The elastase digest of the aortic elastin was chromatographed on a Sephadex G-100 column and separated into two fractions: A (larger molecular weight) and B (smaller molecular weight). The ratio of fraction A to total aortic elastin increased with age and the development of the atherosclerosis. Amino acid and sugar analyses showed that fraction A consistently contained more polar amino acids, hexose, hexosamine and L-fucose, and less sialic acid, in comparison with fraction B. Part of the elastin preparation was incubated with human low-density lipoprotein; a considerable amount of lipid, especially cholesterol, was transferred from the lipoprotein to the elastin. Estimation of protein and cholesterol in fractions A and B of the elastase hydrolyzate of incubated elastin showed that most of the cholesterol taken up by elastin had been in fraction A. The increased proportion of fraction A in aortic elastin derived from plaque areas appeared responsible for the marked lipid-binding capacity of plaque elastin."}
{"id": "PMID:199207", "title": "Biochemical and immunological evidence for the presence of an apolipoprotein B-like component in the serum low-density lipoproteins of several animal species.", "content": "The major component of the protein moiety of human LDL, i.e. apolipoprotein B, has been compared biochemically and immunologically with its counterpart in the LDL of several groups of animals (mammals, birds, snakes and fish). A marked resemblance was found in the amino acid composition of the apo-B fractions from all the phylogenetic groups, although immunological cross-reactivity with human apolipoprotein B occurred only in the case of non-human primate (Old World monkey), non-primate mammalian (pig and guinea pig) and bird (chicken) apo-B components (63%, 24% and about 8% respectively). The cross-reactivity of each animal apo-B component with its human counterpart was 7-14% lower than that observed between the parent LDL's. The resemblance in amino acid composition between the various apo-B preparations suggests that certain structural characteristics are required in this protein in order for it to bind and stabilise the lipid complement of serum LDL.", "contents": "Biochemical and immunological evidence for the presence of an apolipoprotein B-like component in the serum low-density lipoproteins of several animal species. The major component of the protein moiety of human LDL, i.e. apolipoprotein B, has been compared biochemically and immunologically with its counterpart in the LDL of several groups of animals (mammals, birds, snakes and fish). A marked resemblance was found in the amino acid composition of the apo-B fractions from all the phylogenetic groups, although immunological cross-reactivity with human apolipoprotein B occurred only in the case of non-human primate (Old World monkey), non-primate mammalian (pig and guinea pig) and bird (chicken) apo-B components (63%, 24% and about 8% respectively). The cross-reactivity of each animal apo-B component with its human counterpart was 7-14% lower than that observed between the parent LDL's. The resemblance in amino acid composition between the various apo-B preparations suggests that certain structural characteristics are required in this protein in order for it to bind and stabilise the lipid complement of serum LDL."}
{"id": "PMID:199208", "title": "[Wilms' tumor, multiple intestinal parasitosis and typhoid fever].", "content": "The case was that of a 21-month-old infant who presented a great inoperable Wilm's tumor that was treated with vincristine to the point of practically disappearing. Severe typhoid fever that was complicated by multiple intestinal parasitoses (ascariasis, trichuriasis, giardiasis and strongyloidiasis) appeared. Possibly, tumoral necrosis, salmonellosis and the parasitoses formed a sac that opened to the hepatic angle of the colon. Finally, multiple liver metastases were discovered and confirmed pathologically. The patient died 36 hours after surgical reexamination and liver biopsies, from causes not clearly explained. Comments are made on the diagnostic problems originated by rareness of the association of typhoid fever resistant to chloramphenicol, intestinal parasitoses and a great Wilms' tumor and the possible influence of chemotherapy and radiotherapy in the evolution of the case.", "contents": "[Wilms' tumor, multiple intestinal parasitosis and typhoid fever]. The case was that of a 21-month-old infant who presented a great inoperable Wilm's tumor that was treated with vincristine to the point of practically disappearing. Severe typhoid fever that was complicated by multiple intestinal parasitoses (ascariasis, trichuriasis, giardiasis and strongyloidiasis) appeared. Possibly, tumoral necrosis, salmonellosis and the parasitoses formed a sac that opened to the hepatic angle of the colon. Finally, multiple liver metastases were discovered and confirmed pathologically. The patient died 36 hours after surgical reexamination and liver biopsies, from causes not clearly explained. Comments are made on the diagnostic problems originated by rareness of the association of typhoid fever resistant to chloramphenicol, intestinal parasitoses and a great Wilms' tumor and the possible influence of chemotherapy and radiotherapy in the evolution of the case."}
{"id": "PMID:199209", "title": "[Juvenile nasopharyngeal angiofibroma with intracraneal lesion. Report of a case].", "content": "A case of juvenile nasopharyngeal angiofibroma in a 9 years and 8 months old male child is reported. Histologically it is considered a mild tumor, but because of its rapid growth and great surgical risk, it is clinically considered malignant. Surgery is the most important factor.", "contents": "[Juvenile nasopharyngeal angiofibroma with intracraneal lesion. Report of a case]. A case of juvenile nasopharyngeal angiofibroma in a 9 years and 8 months old male child is reported. Histologically it is considered a mild tumor, but because of its rapid growth and great surgical risk, it is clinically considered malignant. Surgery is the most important factor."}
{"id": "PMID:199210", "title": "[Review of 15 cases of hypervitaminosis D].", "content": "In our experience, hypervitaminosis D, which at present should only be a historic remembrance in pediatrics, is still a frequent cause of hipercalcemia in childhood. It is easy understand that its appearance should turn out to be a complication in the treatment of hypoparathyroidisms or in vitamin D resistant rickets, but its persistance as a purely iatrogenic diseases is at present inexplicable. The frequency with which we have seen it has led us to review 15 cases where erroneous administration of high doses of vitamin D has resulted in serious clinical, biological and anatomical problems.", "contents": "[Review of 15 cases of hypervitaminosis D]. In our experience, hypervitaminosis D, which at present should only be a historic remembrance in pediatrics, is still a frequent cause of hipercalcemia in childhood. It is easy understand that its appearance should turn out to be a complication in the treatment of hypoparathyroidisms or in vitamin D resistant rickets, but its persistance as a purely iatrogenic diseases is at present inexplicable. The frequency with which we have seen it has led us to review 15 cases where erroneous administration of high doses of vitamin D has resulted in serious clinical, biological and anatomical problems."}
{"id": "PMID:199211", "title": "[Rotavirus in children with severe malnutrition].", "content": "The study comprised 19 children with severe protein-calorie malnutrition admitted to Hospital Nacional de Ni\u00f1os. With one exception, all of the patients complained of diarrhea at the examination. Samples of stools were collected for bacteriologic, parasitologic and virologic studies. Rotavirus was shown in 4 cases and adenovirus in another 4. Enteropathogenic Escherichia coli, Shigella and Salmonella were isolated in 9 different children. It was possible to demonstrate at least one potentially pathogenic agent in 84% of the total number of cases. In malnourished infants under one year of age, the index of positiveness was 100%. It is set forth that infection is the most important factor in the etiology of diarrhea of the malnourished infant.", "contents": "[Rotavirus in children with severe malnutrition]. The study comprised 19 children with severe protein-calorie malnutrition admitted to Hospital Nacional de Ni\u00f1os. With one exception, all of the patients complained of diarrhea at the examination. Samples of stools were collected for bacteriologic, parasitologic and virologic studies. Rotavirus was shown in 4 cases and adenovirus in another 4. Enteropathogenic Escherichia coli, Shigella and Salmonella were isolated in 9 different children. It was possible to demonstrate at least one potentially pathogenic agent in 84% of the total number of cases. In malnourished infants under one year of age, the index of positiveness was 100%. It is set forth that infection is the most important factor in the etiology of diarrhea of the malnourished infant."}
{"id": "PMID:199220", "title": "The effect of age on the safety factor in neuromuscular transmission in the isolated diaphragm of the rat.", "content": "An analysis of neuromuscular transmission has been made in phrenic nerve/diaphragm preparations from male rats aged 30 days or 110 days. The amplitude of miniature end-plate potentials was found to decrease with age, being 0.969 +/- SEM 0.058 mV at 30 days and 0.510 +/- SEM 0.031 mV at 110 days. Over the same period, the quantum content of the first end-plate potential of a train of 40 at 10 Hz, increased from 144.5, SEM + 11.1, -10.4 to 346, SEM +41.4, -37.0. A corresponding change was observed also in the average quantum contents of the last 30 end-plate potentials of each train; from 50.6, SEM +3.5, -3.2, to 138.9, SEM + 15.0,--13.6. The safety factor for neuromuscular transmission, calculated from these measured parameters, was found at 30 days to be only 70-80% of that at 110 days. It was estimated that the lower safety factor found in young rats was approximately equivalent to the neuromuscular blocking action of a dose of, at least, 0.0225 mg/kg of d-tubocurarine. Extrapolation of these results to man would support previous reports of increased sensitivity to d-tubocurarine in neonates.", "contents": "The effect of age on the safety factor in neuromuscular transmission in the isolated diaphragm of the rat. An analysis of neuromuscular transmission has been made in phrenic nerve/diaphragm preparations from male rats aged 30 days or 110 days. The amplitude of miniature end-plate potentials was found to decrease with age, being 0.969 +/- SEM 0.058 mV at 30 days and 0.510 +/- SEM 0.031 mV at 110 days. Over the same period, the quantum content of the first end-plate potential of a train of 40 at 10 Hz, increased from 144.5, SEM + 11.1, -10.4 to 346, SEM +41.4, -37.0. A corresponding change was observed also in the average quantum contents of the last 30 end-plate potentials of each train; from 50.6, SEM +3.5, -3.2, to 138.9, SEM + 15.0,--13.6. The safety factor for neuromuscular transmission, calculated from these measured parameters, was found at 30 days to be only 70-80% of that at 110 days. It was estimated that the lower safety factor found in young rats was approximately equivalent to the neuromuscular blocking action of a dose of, at least, 0.0225 mg/kg of d-tubocurarine. Extrapolation of these results to man would support previous reports of increased sensitivity to d-tubocurarine in neonates."}
{"id": "PMID:199222", "title": "Studies on brain metabolism of biogenic amines.", "content": "1. In vitro models (synaptosones, electrically stimulated brain slices and monoamine oxidase (MAO) preparations have been used to identify the sites of action of nomifensine on brain monoamine metabolism. 2. Nomifensine potentiates neurotransmission in noradrenergic and dopaminergic synapses by blocking catecholamine uptake. 3. Nomifensine does not inhibit MAO and does not enhance the release of biogenic amines. 4. Studies on electrically stimulated brain slices suggest that nomifensine does not directly stimulate dopamine (DA) nor noradrenaline (NA) receptor sites. 5. 5-Hydroxytryptamine (5-HT) uptake is not inhibited at \"therapeutic\" concentrations of nomifensine. 6. Nomifensine differs from the tricyclic antidepressants by virtue of its effect on the dopaminergic system.", "contents": "Studies on brain metabolism of biogenic amines. 1. In vitro models (synaptosones, electrically stimulated brain slices and monoamine oxidase (MAO) preparations have been used to identify the sites of action of nomifensine on brain monoamine metabolism. 2. Nomifensine potentiates neurotransmission in noradrenergic and dopaminergic synapses by blocking catecholamine uptake. 3. Nomifensine does not inhibit MAO and does not enhance the release of biogenic amines. 4. Studies on electrically stimulated brain slices suggest that nomifensine does not directly stimulate dopamine (DA) nor noradrenaline (NA) receptor sites. 5. 5-Hydroxytryptamine (5-HT) uptake is not inhibited at \"therapeutic\" concentrations of nomifensine. 6. Nomifensine differs from the tricyclic antidepressants by virtue of its effect on the dopaminergic system."}
{"id": "PMID:199223", "title": "Comparison of cell-surface glycoproteins of rat hepatomas and embryonic rat liver.", "content": "Cell-surface glycoprotein of 3 rat hepatoma strains and late-embryonic liver was metabolically labelled in vivo with [3H]- or [14C]-fucose. Trypsinization of the cells and exhaustive pronase digestion of combined hepatoma-liver trypsinates followed by gel filtration over Sephadex-Biogel mixtures, yielded elution profiles that contained more early-eluting (high-mol.-wt.) glycopeptides for hepatomas than for liver. At least 3 factors were identified which acted to augment the fraction of early-eluting tumour glycopeptides: (a) increase of neuraminidase-sensitive sialic acid, (b) increase of neuraminidase-insensitive sialic acid that was sensitive to mild HCl hydrolysis, and (c) presence of sugar sulphate groups contributing to a restricted extent, relative to possible unknown factor(s). Whether (a), (b) or (c) operated depended on the hepatoma strain or its mode of growth. Notwithstanding these differences in the nature of the increase in early-eluting glycopeptides, the increase itself appears not to be due to growth per se, nor to an embryonic expression, but rather may serve as a marker of tumourigenicity.", "contents": "Comparison of cell-surface glycoproteins of rat hepatomas and embryonic rat liver. Cell-surface glycoprotein of 3 rat hepatoma strains and late-embryonic liver was metabolically labelled in vivo with [3H]- or [14C]-fucose. Trypsinization of the cells and exhaustive pronase digestion of combined hepatoma-liver trypsinates followed by gel filtration over Sephadex-Biogel mixtures, yielded elution profiles that contained more early-eluting (high-mol.-wt.) glycopeptides for hepatomas than for liver. At least 3 factors were identified which acted to augment the fraction of early-eluting tumour glycopeptides: (a) increase of neuraminidase-sensitive sialic acid, (b) increase of neuraminidase-insensitive sialic acid that was sensitive to mild HCl hydrolysis, and (c) presence of sugar sulphate groups contributing to a restricted extent, relative to possible unknown factor(s). Whether (a), (b) or (c) operated depended on the hepatoma strain or its mode of growth. Notwithstanding these differences in the nature of the increase in early-eluting glycopeptides, the increase itself appears not to be due to growth per se, nor to an embryonic expression, but rather may serve as a marker of tumourigenicity."}
{"id": "PMID:199224", "title": "Radioiodination studies of tumour cell-surface proteins after different disaggregation procedures.", "content": "The surface of single cells isolated from solid tumours by either a mechanical or an enzymatic method have been compared, using lactoperoxidase-catalyzed radioiodination of the tyrosine-containing proteins. Qualitatively, the patterns of surface labelling were similar, and duplicate experiments indicated that each method of isolation gave reproducible results. Analysis of incorporated label into 4 defined sections of the electrophoretic pattern illustrated quantitative differences. When the cells were isolated mechanically, the incorporation into low-mol.- wt. components was considerably reduced, whereas that into the high-mol.-wt. components was unaffected. Treatment of enzymatically isolated cells with trypsin also reduced incorporation into low-mol.-wt components.", "contents": "Radioiodination studies of tumour cell-surface proteins after different disaggregation procedures. The surface of single cells isolated from solid tumours by either a mechanical or an enzymatic method have been compared, using lactoperoxidase-catalyzed radioiodination of the tyrosine-containing proteins. Qualitatively, the patterns of surface labelling were similar, and duplicate experiments indicated that each method of isolation gave reproducible results. Analysis of incorporated label into 4 defined sections of the electrophoretic pattern illustrated quantitative differences. When the cells were isolated mechanically, the incorporation into low-mol.- wt. components was considerably reduced, whereas that into the high-mol.-wt. components was unaffected. Treatment of enzymatically isolated cells with trypsin also reduced incorporation into low-mol.-wt components."}
{"id": "PMID:199225", "title": "Null-cell properties of a lymphoid cell line from a child with acute lymphoblastic leukaemia.", "content": "Cultured cells established from the bone marrow of a child with null-cell acute lymphoblastic leukaemia (ALL) have been studied. After 8 months in vitro, the cytological, cytochemical and immunological properties of the cultured cells were very similar to those of the patient's cells. Many of the cultured cells had morphological and cytogenetic abnormalities often found in acute leukaemia. The cells were EBNA-negative. This unique culture of ALL-derived null cells might provide information as to the aetiology and origin of malignant cells.", "contents": "Null-cell properties of a lymphoid cell line from a child with acute lymphoblastic leukaemia. Cultured cells established from the bone marrow of a child with null-cell acute lymphoblastic leukaemia (ALL) have been studied. After 8 months in vitro, the cytological, cytochemical and immunological properties of the cultured cells were very similar to those of the patient's cells. Many of the cultured cells had morphological and cytogenetic abnormalities often found in acute leukaemia. The cells were EBNA-negative. This unique culture of ALL-derived null cells might provide information as to the aetiology and origin of malignant cells."}
{"id": "PMID:199226", "title": "Hepatic cell loss and proliferation induced by N-2-fluorenylacetamide, diethylnitrosamine, and aflatoxin B1 in relation to hepatoma induction.", "content": "Three hepatic carcinogens (aflatoxin B1, diethylnitrosamine (DEN) and N-2-fluorenylacetamide (FAA)) were compared for carcinogenicity, early cell toxicity and parenchymal cell proliferation. The carcinogens were administered to rats for 15 weeks as follows: aflatoxin B1, 1 in 10(6) in pelleted food; DEN, 2 in 10(5) in drinking water; FAA, 3 in 10(4) in pelleted food. The loss of prelabelled DNA and the [H3] TdR pulse-labelling indices (LI) of parenchymal and nonparenchymal cells were determined at various times during the period of carcinogen availability. On a molar basis, aflatoxin B1 was 90 times as carcinogenic as FAA and 24 times as carcinogenic as DEN. However, for about equal magnitudes of hepatic cell proliferation and loss, aflatoxin B1 was the least potent carcinogen. For a given level of carcinogenicity, FAA was more potent than DEN in causing loss of hepatic DNA and in increasing the parenchymal cell labelling index. DEN and aflatoxin B1 produced about the same degree of DNA loss and parenchymal cell labelling, but the former was a more potent carcinogen. When carcinogenicity was compared for approximately equal levels of early hepatic cell destruction and proliferation, the 3 chemicals in the present study could be ranked in descending order of potency as DEN, FAA and aflatoxin B1.", "contents": "Hepatic cell loss and proliferation induced by N-2-fluorenylacetamide, diethylnitrosamine, and aflatoxin B1 in relation to hepatoma induction. Three hepatic carcinogens (aflatoxin B1, diethylnitrosamine (DEN) and N-2-fluorenylacetamide (FAA)) were compared for carcinogenicity, early cell toxicity and parenchymal cell proliferation. The carcinogens were administered to rats for 15 weeks as follows: aflatoxin B1, 1 in 10(6) in pelleted food; DEN, 2 in 10(5) in drinking water; FAA, 3 in 10(4) in pelleted food. The loss of prelabelled DNA and the [H3] TdR pulse-labelling indices (LI) of parenchymal and nonparenchymal cells were determined at various times during the period of carcinogen availability. On a molar basis, aflatoxin B1 was 90 times as carcinogenic as FAA and 24 times as carcinogenic as DEN. However, for about equal magnitudes of hepatic cell proliferation and loss, aflatoxin B1 was the least potent carcinogen. For a given level of carcinogenicity, FAA was more potent than DEN in causing loss of hepatic DNA and in increasing the parenchymal cell labelling index. DEN and aflatoxin B1 produced about the same degree of DNA loss and parenchymal cell labelling, but the former was a more potent carcinogen. When carcinogenicity was compared for approximately equal levels of early hepatic cell destruction and proliferation, the 3 chemicals in the present study could be ranked in descending order of potency as DEN, FAA and aflatoxin B1."}
{"id": "PMID:199228", "title": "The effect of macrophage poisoning by silica on experimental pulmonary contusion and its benzo-pyrone treatment.", "content": "The effect of poisoning the macrophages with silica on the fine structure of pulmonary contusion was studied in rats. It was found that this causes an increase in the concentration of protein in the interstitial tissue and in the air spaces. It also causes a consequent increase in the amount of interstitial oedema. While the benzo-pyrones normally cause a considerable reduction both in the protein concentrations and in the amount of oedema, they do not act in these ways when the macrophages are poisoned. These results imply that the macrophages normally lyse some of the protein and that this effect is considerably enhanced by the action of the benzo-pyrones.", "contents": "The effect of macrophage poisoning by silica on experimental pulmonary contusion and its benzo-pyrone treatment. The effect of poisoning the macrophages with silica on the fine structure of pulmonary contusion was studied in rats. It was found that this causes an increase in the concentration of protein in the interstitial tissue and in the air spaces. It also causes a consequent increase in the amount of interstitial oedema. While the benzo-pyrones normally cause a considerable reduction both in the protein concentrations and in the amount of oedema, they do not act in these ways when the macrophages are poisoned. These results imply that the macrophages normally lyse some of the protein and that this effect is considerably enhanced by the action of the benzo-pyrones."}
{"id": "PMID:199230", "title": "Pregnancy complicated by insulinoma. Case report.", "content": "An insulinoma was excised during pregnancy. The tumor was located by radiography and severe hypoglycaemia made it necessary to administer diazoxide to the mother. The out come in the pregnancy was satisfactory. The rationale and risks of giving diazoxide in pregnancy are discussed.", "contents": "Pregnancy complicated by insulinoma. Case report. An insulinoma was excised during pregnancy. The tumor was located by radiography and severe hypoglycaemia made it necessary to administer diazoxide to the mother. The out come in the pregnancy was satisfactory. The rationale and risks of giving diazoxide in pregnancy are discussed."}
{"id": "PMID:199231", "title": "Hydatidiform mole arising twice during bromocriptine therapy. Case report.", "content": "A patient with a prolactin secreting pituitary tumour is described, in whom two pregnancies occurred during bromocriptine treatment. Both were hydatidiform moles.", "contents": "Hydatidiform mole arising twice during bromocriptine therapy. Case report. A patient with a prolactin secreting pituitary tumour is described, in whom two pregnancies occurred during bromocriptine treatment. Both were hydatidiform moles."}
{"id": "PMID:199232", "title": "Effect of phosphonoacetic acid in the treatment of experimental herpes simplex keratitis.", "content": "In the rabbit 5% phosphonoacetic acid ointment suppressed herpetic keratitis as well as 0-5% idoxuridine ointment. After 5 days of treatment quantitative virus titres showed that phosphonoacetic acid was superior to idoxuridine in the inhibition of herpes virus replication. Phosphonoacetic acid was found to be nontoxic to the eye in both clinical and histopathological studies. Recent reports suggest that the mechanism of action of phosphonoacetic acid appears to be the blocking of the virus DNA polymerase, which is essential for the synthesis of herpes virus DNA.", "contents": "Effect of phosphonoacetic acid in the treatment of experimental herpes simplex keratitis. In the rabbit 5% phosphonoacetic acid ointment suppressed herpetic keratitis as well as 0-5% idoxuridine ointment. After 5 days of treatment quantitative virus titres showed that phosphonoacetic acid was superior to idoxuridine in the inhibition of herpes virus replication. Phosphonoacetic acid was found to be nontoxic to the eye in both clinical and histopathological studies. Recent reports suggest that the mechanism of action of phosphonoacetic acid appears to be the blocking of the virus DNA polymerase, which is essential for the synthesis of herpes virus DNA."}
{"id": "PMID:199236", "title": "Role of coenzyme Q in the mitochondrial respiratory chain. Reconstitution of activity in coenzyme Q deficient mutants of yeast.", "content": "The reduction of cytochrome c by the reduced form of the 6-decyl analogue of coenzyme Q follows first-order kinetics with respect to cytochrome c and increases in a linear manner with added mitochondrial protein. The activity is completely sensitive to antimycin A in whole cell extracts of yeast as well as in isolated mitochondria and fractionates with markers for the mitochondrial electron-transport chain. The presence of both cytochrome b and c1 in an approximately 2:1 ratio appears essential for enzymatic activity. Reduced coenzyme Q-cytochrome c reductase obeys Michaelis-Menten kinetics when assayed in mitochondria obtained from a yeast strain lacking coenzyme Q. Both reduced nitotinamide adenine dinucleotide and succinate:cytochrome c reductase activities were not detectable in six coenzyme Q deficient strains tested, but were restored after addition of the oxidized form of the coenzyme Q analogue. No marked difference in the concentration of the analogue required to restore the two activities was observed.", "contents": "Role of coenzyme Q in the mitochondrial respiratory chain. Reconstitution of activity in coenzyme Q deficient mutants of yeast. The reduction of cytochrome c by the reduced form of the 6-decyl analogue of coenzyme Q follows first-order kinetics with respect to cytochrome c and increases in a linear manner with added mitochondrial protein. The activity is completely sensitive to antimycin A in whole cell extracts of yeast as well as in isolated mitochondria and fractionates with markers for the mitochondrial electron-transport chain. The presence of both cytochrome b and c1 in an approximately 2:1 ratio appears essential for enzymatic activity. Reduced coenzyme Q-cytochrome c reductase obeys Michaelis-Menten kinetics when assayed in mitochondria obtained from a yeast strain lacking coenzyme Q. Both reduced nitotinamide adenine dinucleotide and succinate:cytochrome c reductase activities were not detectable in six coenzyme Q deficient strains tested, but were restored after addition of the oxidized form of the coenzyme Q analogue. No marked difference in the concentration of the analogue required to restore the two activities was observed."}
{"id": "PMID:199238", "title": "Pulse fluorimetry study of octopine dehydrogenase-reduced nicotinamide adenine dinucleotide complexes.", "content": "We measured the transient fluorescence of NADH bound to octopine dehydrogenase in the binary octopine dehydrogenase-NADH complex and in the ternary complexes containing D-octopine, L-allooctopine, L-arginine, D-arginine, or 5-guanidinovaleric acid. The fluorescence decay in all these complexes is biexponential. This is explained by the presence of several conformations of the single NADH binding site. In addition, transietn anisotropy measurements show that the nicotinamide moiety is rigidly bound to the enzyme.", "contents": "Pulse fluorimetry study of octopine dehydrogenase-reduced nicotinamide adenine dinucleotide complexes. We measured the transient fluorescence of NADH bound to octopine dehydrogenase in the binary octopine dehydrogenase-NADH complex and in the ternary complexes containing D-octopine, L-allooctopine, L-arginine, D-arginine, or 5-guanidinovaleric acid. The fluorescence decay in all these complexes is biexponential. This is explained by the presence of several conformations of the single NADH binding site. In addition, transietn anisotropy measurements show that the nicotinamide moiety is rigidly bound to the enzyme."}
{"id": "PMID:199243", "title": "Effects of neuraminidase on lectin binding by wild-type and ricin-resistant strains of hamster fibroblasts.", "content": "The nature of cell surface receptors for ricin on wild-type and ricin-resistant variants of baby hamster kidney fibroblasts has been studied. Neuraminidase stimulated ricin binding threefold by wild-type cells, and increased their susceptibility to ricin toxicity as measured by inhibition of [3H]leucine uptake (LD30 fell from 5.0 to 0.5 microgram/mL). Basal ricin binding by ricin-resistant variants (10-300% that of wild type) was also stimulated (2- to 17-fold) by neuraminidase in all seven clonal strains examined; susceptibility to ricin was greatly increased by neuraminidase in these variants. Neuraminidase did not affect the binding of concanavalin A by wild type or a ricin-resistant variant, but decreased the binding of wheat-germ agglutinin by 90% in both cell types. The trivial binding of peanut agglutinin by wild type and a ricin-resistant variant was markedly enhanced (14- to 22-fold) by neuraminidase. Neither collagenase (50 U/mL) nor Pronase (0.0001%) affected ricin binding by wild type or a ricin-resistant variant. These data suggest the existence of \"exposed\" and \"cryptic\" oligosaccharide receptors for ricin on the cell membrane glycoproteins of baby hamster kidney fibroblasts. The cryptic ricin receptors probably include at least the sequence D-galactosyl-beta-(1 replaced by 3)-N-acetylhexosamine substituted by sialic acid residues. Exposed and cryptic ricin receptors appear to be different and under separate genetic control.", "contents": "Effects of neuraminidase on lectin binding by wild-type and ricin-resistant strains of hamster fibroblasts. The nature of cell surface receptors for ricin on wild-type and ricin-resistant variants of baby hamster kidney fibroblasts has been studied. Neuraminidase stimulated ricin binding threefold by wild-type cells, and increased their susceptibility to ricin toxicity as measured by inhibition of [3H]leucine uptake (LD30 fell from 5.0 to 0.5 microgram/mL). Basal ricin binding by ricin-resistant variants (10-300% that of wild type) was also stimulated (2- to 17-fold) by neuraminidase in all seven clonal strains examined; susceptibility to ricin was greatly increased by neuraminidase in these variants. Neuraminidase did not affect the binding of concanavalin A by wild type or a ricin-resistant variant, but decreased the binding of wheat-germ agglutinin by 90% in both cell types. The trivial binding of peanut agglutinin by wild type and a ricin-resistant variant was markedly enhanced (14- to 22-fold) by neuraminidase. Neither collagenase (50 U/mL) nor Pronase (0.0001%) affected ricin binding by wild type or a ricin-resistant variant. These data suggest the existence of \"exposed\" and \"cryptic\" oligosaccharide receptors for ricin on the cell membrane glycoproteins of baby hamster kidney fibroblasts. The cryptic ricin receptors probably include at least the sequence D-galactosyl-beta-(1 replaced by 3)-N-acetylhexosamine substituted by sialic acid residues. Exposed and cryptic ricin receptors appear to be different and under separate genetic control."}
{"id": "PMID:199244", "title": "Oxidative titrations of reduced cytochrome aa3: influence of cytochrome c and carbon monoxide on the midpoint potential values.", "content": "Oxidative titrations were performed on the electrostatic complex formed between cytochrome c and cytochrome aa3 at low ionic strength. Midpoint potentials of the redox centers in the proteins in 1:1 and 2:1 complexes were compared with those in mixtures of the cytochromes at high ionic strength. Computer simulations of all titrations yielded midpoint potentials for the components of cytochrome aa3 which were consistent with literature values for isolated cytochrome aa3 or mixture of cytochromes c and aa3. However, the unequal heme extinction coefficients observed previously (Schroedl, N.A., and Hartzell, C.R. (1977), Biochemistry 16, 1327) during oxidative titrations of cytochrome aa3 became equal in magnitude under these experimental conditions. The binding of cytochrome c to cytochrome aa3 changed the midpoint potentials of cytochrome aa3 by 15-20 mV, while the midpoint potentials for cytochrome c were altered by 50-60 mV. Careful analysis of these titrations including computer simulation revealed that cytochrome c was able to bind to cytochrome aa3 only after cytochrome aL2+ had become oxidized. When bound to cytochrome aa3, the midpoint potential of cytochrome c was 210 7V. Titrations performed under a carbon monoxide atmosphere revealed cytochrome aa3 midpoint potentials unchanged from reported values. Cytochrome c again exhibited a midpoint potential of 210 mV after binding to cytochrome aa3.", "contents": "Oxidative titrations of reduced cytochrome aa3: influence of cytochrome c and carbon monoxide on the midpoint potential values. Oxidative titrations were performed on the electrostatic complex formed between cytochrome c and cytochrome aa3 at low ionic strength. Midpoint potentials of the redox centers in the proteins in 1:1 and 2:1 complexes were compared with those in mixtures of the cytochromes at high ionic strength. Computer simulations of all titrations yielded midpoint potentials for the components of cytochrome aa3 which were consistent with literature values for isolated cytochrome aa3 or mixture of cytochromes c and aa3. However, the unequal heme extinction coefficients observed previously (Schroedl, N.A., and Hartzell, C.R. (1977), Biochemistry 16, 1327) during oxidative titrations of cytochrome aa3 became equal in magnitude under these experimental conditions. The binding of cytochrome c to cytochrome aa3 changed the midpoint potentials of cytochrome aa3 by 15-20 mV, while the midpoint potentials for cytochrome c were altered by 50-60 mV. Careful analysis of these titrations including computer simulation revealed that cytochrome c was able to bind to cytochrome aa3 only after cytochrome aL2+ had become oxidized. When bound to cytochrome aa3, the midpoint potential of cytochrome c was 210 7V. Titrations performed under a carbon monoxide atmosphere revealed cytochrome aa3 midpoint potentials unchanged from reported values. Cytochrome c again exhibited a midpoint potential of 210 mV after binding to cytochrome aa3."}
{"id": "PMID:199245", "title": "Use of specific lysine modifications to locate the reaction site of cytochrome c with cytochrome oxidase.", "content": "The reaction of cytochrome c with trifluoromethylphenyl isocyanate was carried out under conditions which led to the modification of a small number of the 19 lysines. Extensive ion-exchange chromatography was used to separate and purify six different derivatives, each modified at a single lysine residue, lysines 8, 13, 27, 72, 79, and 100, respectively. The only modifications which affected the activity of cytochrome c with cytochrome oxidase (EC 1.9.3.1) were those of lysines immediately surrounding the heme crevice, lysines 13, 27, 72, and 79, and also lysine 8 at the top of the heme crevice. In each case, the modified cytochrome c had the same maximum velocity as that of native cytochrome c, but an increased Michaelis constant for high affinity phase of the reaction. This supports the hypothesis that the cytochrome oxidase reaction site is located in the heme crevice region, and the highly conserved lysine residues surrounding the heme crevice are important in the binding.", "contents": "Use of specific lysine modifications to locate the reaction site of cytochrome c with cytochrome oxidase. The reaction of cytochrome c with trifluoromethylphenyl isocyanate was carried out under conditions which led to the modification of a small number of the 19 lysines. Extensive ion-exchange chromatography was used to separate and purify six different derivatives, each modified at a single lysine residue, lysines 8, 13, 27, 72, 79, and 100, respectively. The only modifications which affected the activity of cytochrome c with cytochrome oxidase (EC 1.9.3.1) were those of lysines immediately surrounding the heme crevice, lysines 13, 27, 72, and 79, and also lysine 8 at the top of the heme crevice. In each case, the modified cytochrome c had the same maximum velocity as that of native cytochrome c, but an increased Michaelis constant for high affinity phase of the reaction. This supports the hypothesis that the cytochrome oxidase reaction site is located in the heme crevice region, and the highly conserved lysine residues surrounding the heme crevice are important in the binding."}
{"id": "PMID:199248", "title": "3'-Phosphatase activity in T4 polynucleotide kinase.", "content": "The purification of T4 polynucleotide kinase results in the copurification of an activity which will specifically remove the 3'-terminal phosphate from a variety of deoxyribonucleotides and ribonucleotides in the absence of ATP. This phosphatase activity requires magnesium, has a pH optiumum of 6.0, and is more active with deoxyribonucleotides than ribonucleotides. T4 polynucleotide kinase and the 3'-phosphatase activity copurify by gradient elution column chromatography on DEAE-cellulose, phosphocellulose, and hydroxylapatite. The two activities are included in and comigrate on Sephadex G-200. Polyacrylamide gel electrophoresis at PH 9.2 results in conigration of the two activities together with the major protein band. The two activities respond in parallel to heat inactivation at 35 degrees C and ATP, a substrate for the kinase only, protects both activities from heat inactivation. It is therefore suggested that the two activities are functions of the same protein molecule.", "contents": "3'-Phosphatase activity in T4 polynucleotide kinase. The purification of T4 polynucleotide kinase results in the copurification of an activity which will specifically remove the 3'-terminal phosphate from a variety of deoxyribonucleotides and ribonucleotides in the absence of ATP. This phosphatase activity requires magnesium, has a pH optiumum of 6.0, and is more active with deoxyribonucleotides than ribonucleotides. T4 polynucleotide kinase and the 3'-phosphatase activity copurify by gradient elution column chromatography on DEAE-cellulose, phosphocellulose, and hydroxylapatite. The two activities are included in and comigrate on Sephadex G-200. Polyacrylamide gel electrophoresis at PH 9.2 results in conigration of the two activities together with the major protein band. The two activities respond in parallel to heat inactivation at 35 degrees C and ATP, a substrate for the kinase only, protects both activities from heat inactivation. It is therefore suggested that the two activities are functions of the same protein molecule."}
{"id": "PMID:199252", "title": "The anaerobic oxidation of dihydroorotate by Escherichia coli K-12.", "content": "The oxidation of dihydroorotate under anaerobic conditions has been examined using various mutant strains of Escherichia coli K-12. This oxidation in cells grown anaerobically in a glucose minimal medium is linked via menaquinone to the fumarate reductase enzyme coded for by the frd gene and is independent of the cytochromes. The same dihydroorotate dehydrogenase protein functions in both the anaerobic and aerobic oxidation of dihydroorotate. Ferricyanide can act as an artificial electron acceptor for dihydroorotate dehydrogenase and the dihydroorotate-menaquinone-ferricyanide reductase activity can be solubilised by 2 M guanidine-HCl with little loss of activity.", "contents": "The anaerobic oxidation of dihydroorotate by Escherichia coli K-12. The oxidation of dihydroorotate under anaerobic conditions has been examined using various mutant strains of Escherichia coli K-12. This oxidation in cells grown anaerobically in a glucose minimal medium is linked via menaquinone to the fumarate reductase enzyme coded for by the frd gene and is independent of the cytochromes. The same dihydroorotate dehydrogenase protein functions in both the anaerobic and aerobic oxidation of dihydroorotate. Ferricyanide can act as an artificial electron acceptor for dihydroorotate dehydrogenase and the dihydroorotate-menaquinone-ferricyanide reductase activity can be solubilised by 2 M guanidine-HCl with little loss of activity."}
{"id": "PMID:199254", "title": "The number of Fe atoms in the iron-sulphur centers of the respiratory chain.", "content": "1. From the 57Fe hyperfine interaction in EPR spectra of reduced submitochondrial particles from the yeast Candida utilis, grown with 57Fe, it is concluded that all Fe-S centers in these particles detectable in spectra at 35-80 K are [2Fe-2S]2-(2-; 3-) centers. These are the centers 1 of NADH and succinate dehydrogenase, the Rieske Fe-S center and possibly center 2 of succinate dehydrogenase. 2. The signals of the reduced particles detectable only at temperatures below 20 K are [4Fe-4S]2-(2-; 3-) clusters. These are the centers 2,3 and 4 of NADH dehydrogenase. 3. EPR spectra of the [2Fe-2S]3- centers of Complex I and II, but not that of Complex III, display a great inequality of the Fe nuclei in the effective hyperfine interaction in the x-y direction.", "contents": "The number of Fe atoms in the iron-sulphur centers of the respiratory chain. 1. From the 57Fe hyperfine interaction in EPR spectra of reduced submitochondrial particles from the yeast Candida utilis, grown with 57Fe, it is concluded that all Fe-S centers in these particles detectable in spectra at 35-80 K are [2Fe-2S]2-(2-; 3-) centers. These are the centers 1 of NADH and succinate dehydrogenase, the Rieske Fe-S center and possibly center 2 of succinate dehydrogenase. 2. The signals of the reduced particles detectable only at temperatures below 20 K are [4Fe-4S]2-(2-; 3-) clusters. These are the centers 2,3 and 4 of NADH dehydrogenase. 3. EPR spectra of the [2Fe-2S]3- centers of Complex I and II, but not that of Complex III, display a great inequality of the Fe nuclei in the effective hyperfine interaction in the x-y direction."}
{"id": "PMID:199255", "title": "The structural transitions of erythrocyte membranes induced by cyclic AMP.", "content": "The generalized structural transitions of erythrocyte membranes induced by cyclic AMP were registered by ESR, fluorescence, freeze-fracture and circular dichroism methods. Two transitions different in nature were revealed. One, which arises at 10-(11)--10-(10) M cyclic AMP, is cooperative and may be considered as a consequence of interaction of cyclic AMP with a receptor. It was calculated that a structural rearrangement in one erythrocyte ghost is induced by three cyclic AMP molecules. As a result of it the membranes are \"loosened\". The other transition arises at 10-(10)--10-(8) M cyclic AMP and depends on the activity of the protein kinase system. This transition was shown to be non-cooperative and due to phosphorylation of membranous proteins. During this rearrangement the membranes are \"stiffened\". Both transitions were demonstrated to relate to the membrane integrity.", "contents": "The structural transitions of erythrocyte membranes induced by cyclic AMP. The generalized structural transitions of erythrocyte membranes induced by cyclic AMP were registered by ESR, fluorescence, freeze-fracture and circular dichroism methods. Two transitions different in nature were revealed. One, which arises at 10-(11)--10-(10) M cyclic AMP, is cooperative and may be considered as a consequence of interaction of cyclic AMP with a receptor. It was calculated that a structural rearrangement in one erythrocyte ghost is induced by three cyclic AMP molecules. As a result of it the membranes are \"loosened\". The other transition arises at 10-(10)--10-(8) M cyclic AMP and depends on the activity of the protein kinase system. This transition was shown to be non-cooperative and due to phosphorylation of membranous proteins. During this rearrangement the membranes are \"stiffened\". Both transitions were demonstrated to relate to the membrane integrity."}
{"id": "PMID:199257", "title": "Regulation of DNA chain elongation in SV3T3 cells in relation to growth rate.", "content": "Regulation of DNA synthesis was investigated in SV40 transformed 3T3 cells exhibiting variable growth rates and residence times in S phase when cultured in the presence of different serum concentrations. Pulse-labeled DNA was chased into large molecular weight material in vivo much more slowly in slowly growing cells than in cells growing at the normal rate. Consistent with this, the joining of short (less than 10 S) chains to form long (greater than 10 S) chains by whole cell lysate system in vitro was greatly impaired in slowly growing cells compared to controls. Thus the lengthening of S phase in SV3T3 cells growing slowly in low serum is reflected in a reduced rate of DNA chain elongation. The presence of cycloheximide during chase in vivo reduced the rate of conversion of pulse-labeled molecules into large molecular weight DNA in both slowly growing and normally growing cells.", "contents": "Regulation of DNA chain elongation in SV3T3 cells in relation to growth rate. Regulation of DNA synthesis was investigated in SV40 transformed 3T3 cells exhibiting variable growth rates and residence times in S phase when cultured in the presence of different serum concentrations. Pulse-labeled DNA was chased into large molecular weight material in vivo much more slowly in slowly growing cells than in cells growing at the normal rate. Consistent with this, the joining of short (less than 10 S) chains to form long (greater than 10 S) chains by whole cell lysate system in vitro was greatly impaired in slowly growing cells compared to controls. Thus the lengthening of S phase in SV3T3 cells growing slowly in low serum is reflected in a reduced rate of DNA chain elongation. The presence of cycloheximide during chase in vivo reduced the rate of conversion of pulse-labeled molecules into large molecular weight DNA in both slowly growing and normally growing cells."}
{"id": "PMID:199258", "title": "Effect of SV40 infection on [3H]uridine incorporation.", "content": "More [3H]uridine was incorporated into RNA of SV40-infected than into uninfected cells 31 h after infection. When the specific activity of the uridine triphosphate pools in infected and uninfected cells was equated by the addition of appropriate amounts of exogenous unlabelled uridine, no difference in the rate of [3H]uridine incorporation into RNA was observed. Although no difference in [3H]uridine entry or phosphorylation was demonstrable, the apparently smaller pools of endogenous RNA precursors in infected cells resulted in less isotope dilution and thus to synthesis of uridine triphosphate and RNA of higher specific activity.", "contents": "Effect of SV40 infection on [3H]uridine incorporation. More [3H]uridine was incorporated into RNA of SV40-infected than into uninfected cells 31 h after infection. When the specific activity of the uridine triphosphate pools in infected and uninfected cells was equated by the addition of appropriate amounts of exogenous unlabelled uridine, no difference in the rate of [3H]uridine incorporation into RNA was observed. Although no difference in [3H]uridine entry or phosphorylation was demonstrable, the apparently smaller pools of endogenous RNA precursors in infected cells resulted in less isotope dilution and thus to synthesis of uridine triphosphate and RNA of higher specific activity."}
{"id": "PMID:199259", "title": "Synthesis and secretion of albumin by a synchronized rat hepatoma cell line.", "content": "The rat hepatoma cell H4-12 which synthesizes and secretes albumin was synchronized by growth in isoleucine-deficient medium followed by a second block with excess thymidine. Albumin synthesis and secretion was measured in the synchronized cells at different time intervals representative of early S, late S, G2, mitosis, early G1 and late G1 phases of the cell cycle. Maximal albumin synthesis occurred during G1 although significant synthesis also occurred during the other cell cyle phases. Most (75--80%) of the radioactive albumin produced during a 15 min pulse incubation with L-[4,5-3H] leucine was found in the microsomal cell fraction and this nascent albumin was secreted into the incubation medium during a 160 min chase period. Fifty percent of the nascent albumin was secreted by 50--55 min and this pattern of secretion did not change during the cell cycle. These data indicate that albumin synthesis occurs throughout the cell cycle but that it is preferred during G1. The rate of intracellular transport and secretion of albumin does not vary during the different phase of the cell cycle.", "contents": "Synthesis and secretion of albumin by a synchronized rat hepatoma cell line. The rat hepatoma cell H4-12 which synthesizes and secretes albumin was synchronized by growth in isoleucine-deficient medium followed by a second block with excess thymidine. Albumin synthesis and secretion was measured in the synchronized cells at different time intervals representative of early S, late S, G2, mitosis, early G1 and late G1 phases of the cell cycle. Maximal albumin synthesis occurred during G1 although significant synthesis also occurred during the other cell cyle phases. Most (75--80%) of the radioactive albumin produced during a 15 min pulse incubation with L-[4,5-3H] leucine was found in the microsomal cell fraction and this nascent albumin was secreted into the incubation medium during a 160 min chase period. Fifty percent of the nascent albumin was secreted by 50--55 min and this pattern of secretion did not change during the cell cycle. These data indicate that albumin synthesis occurs throughout the cell cycle but that it is preferred during G1. The rate of intracellular transport and secretion of albumin does not vary during the different phase of the cell cycle."}
{"id": "PMID:199260", "title": "Different responses to some stimulators of prolyl hydroxylase activities in various rat organs.", "content": "Prolyl hydroxylase (proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) of soluble fraction (105 000 X g supernatant) of rat granulation tissues was markedly enhanced by addition of nucleoside triphosphates to the assay medium. But the stimulatory activities of nucleoside triphosphates were very different in fractions derived from tissues of rat. In skin, lung or whole fetal tissues other than granuloma, GTP enhanced the enzymatic activity by 3-4 fold. On the other hand, in kidney, liver and spleen tissues it brought about no enhancement. The same results were obtained even if ATP regenerating system was added in the assay medium. The stimulatory effect of nucleoside triphosphates was not seen with the soluble fraction of liver, but it appeared with the enzyme fraction purified by affinity column chromatography. The same phenomenon was observed by addition of bovine serum albumin instead of nucleoside triphosphates as stimulator. We discuss the possible reasons as to why the responses of the enzyme to stimulators were quite different among various tissues.", "contents": "Different responses to some stimulators of prolyl hydroxylase activities in various rat organs. Prolyl hydroxylase (proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) of soluble fraction (105 000 X g supernatant) of rat granulation tissues was markedly enhanced by addition of nucleoside triphosphates to the assay medium. But the stimulatory activities of nucleoside triphosphates were very different in fractions derived from tissues of rat. In skin, lung or whole fetal tissues other than granuloma, GTP enhanced the enzymatic activity by 3-4 fold. On the other hand, in kidney, liver and spleen tissues it brought about no enhancement. The same results were obtained even if ATP regenerating system was added in the assay medium. The stimulatory effect of nucleoside triphosphates was not seen with the soluble fraction of liver, but it appeared with the enzyme fraction purified by affinity column chromatography. The same phenomenon was observed by addition of bovine serum albumin instead of nucleoside triphosphates as stimulator. We discuss the possible reasons as to why the responses of the enzyme to stimulators were quite different among various tissues."}
{"id": "PMID:199262", "title": "Cyclic 3':5'-nucleotide phosphodiesterase determined in various human tissues by DEAE-cellulose chromatography.", "content": "Tissue extracts from human heart, lung, liver, kidney, skeletal muscle and cerebrum displayed at least 3 distinct cyclic 3':5'-nucleotide phosphodieterase (EC 3.1.4.17) activity peaks (FI, FII, FIII) on DEAE-cellulose chromatography and various properties of these forms were compared in each tissue. FI eluted at about 0.08 M sodium acetate, hydrolyzed cyclic GMP more rapidly than it did cyclic AMP, and cyclic GMP hydrolysis by FI in most tissues was enhanced by a protein activator in the presence of CaCl2. As only high concentrations of cyclic AMP inhibited cyclic GMP hydrolytic activity of FI, the enzyme probably has a low affinity for cyclic AMP. FII eluted at about 0.2 M sodium acetate, hydrolyzed both nucleotides at equal rates, and substrate affinities were relatively low. Cyclic GMP hydrolysis by FII was also stimulated by addition of a protein activator in the presence of CaCl2 and cyclic AMP hydrolysis in this fraction was accelerated by a micromolar fraction of cyclic GMP. FII eluted at about 0.35 M hydrolyzed cyclic AMP preferentially and was insensitive to protein activator. These two cyclic nucleotides act as mutual inhibitors of the hydrolysis in this fraction. Ratio of the cyclic GMP to cyclic AMP hydrolysis was in the order FI, FII, FIII. Four activity peaks were eluted from the cerebral extract and enzymes from this tissue exhibited much the same properties as observed in the other tissues examined herein.", "contents": "Cyclic 3':5'-nucleotide phosphodiesterase determined in various human tissues by DEAE-cellulose chromatography. Tissue extracts from human heart, lung, liver, kidney, skeletal muscle and cerebrum displayed at least 3 distinct cyclic 3':5'-nucleotide phosphodieterase (EC 3.1.4.17) activity peaks (FI, FII, FIII) on DEAE-cellulose chromatography and various properties of these forms were compared in each tissue. FI eluted at about 0.08 M sodium acetate, hydrolyzed cyclic GMP more rapidly than it did cyclic AMP, and cyclic GMP hydrolysis by FI in most tissues was enhanced by a protein activator in the presence of CaCl2. As only high concentrations of cyclic AMP inhibited cyclic GMP hydrolytic activity of FI, the enzyme probably has a low affinity for cyclic AMP. FII eluted at about 0.2 M sodium acetate, hydrolyzed both nucleotides at equal rates, and substrate affinities were relatively low. Cyclic GMP hydrolysis by FII was also stimulated by addition of a protein activator in the presence of CaCl2 and cyclic AMP hydrolysis in this fraction was accelerated by a micromolar fraction of cyclic GMP. FII eluted at about 0.35 M hydrolyzed cyclic AMP preferentially and was insensitive to protein activator. These two cyclic nucleotides act as mutual inhibitors of the hydrolysis in this fraction. Ratio of the cyclic GMP to cyclic AMP hydrolysis was in the order FI, FII, FIII. Four activity peaks were eluted from the cerebral extract and enzymes from this tissue exhibited much the same properties as observed in the other tissues examined herein."}
{"id": "PMID:199263", "title": "Activation of low molecular weight acid phosphatase from bovine brain by purines and glycerol.", "content": "Low molecular weight acid phosphatase (orthophosphoric monoester phosphophydrolase (acid optimum), EC 3.1.3.2) from bovine brain is activated up to 4-fold by guanosine, guanine, adenine, adenosine, and 6-ethylmercapto-purine. Several pyrimidines and other purines were tested and did not show any activation effect. The rate enhancement induced by purines is uncompetitive and not caused by transphosphorylation to the activator. Using transphosphorylation to glycerol as a probe, it is proposed that the activator binds to one of the phosphorylated intermediates in the reaction pathway. These findings are discussed in terms of the catalytic mechanism of low molecular weight acid phosphatase.", "contents": "Activation of low molecular weight acid phosphatase from bovine brain by purines and glycerol. Low molecular weight acid phosphatase (orthophosphoric monoester phosphophydrolase (acid optimum), EC 3.1.3.2) from bovine brain is activated up to 4-fold by guanosine, guanine, adenine, adenosine, and 6-ethylmercapto-purine. Several pyrimidines and other purines were tested and did not show any activation effect. The rate enhancement induced by purines is uncompetitive and not caused by transphosphorylation to the activator. Using transphosphorylation to glycerol as a probe, it is proposed that the activator binds to one of the phosphorylated intermediates in the reaction pathway. These findings are discussed in terms of the catalytic mechanism of low molecular weight acid phosphatase."}
{"id": "PMID:199265", "title": "Evidence for mammalian collagenases as zinc ion metalloenzymes.", "content": "Collagenases (EC 3.4.24.3) from human skin, rat skin and rat uterus were inhibited by the chelating agents EDTA, 1,10-phenanthroline and tetraethylene pentamine in the presence of excess Ca2+, suggesting that a second metal ion participates in the activity of the enzyme. Collagenase inhibition by 1,10-phenanthroline could be both prevented and reversed by a number of transition metal ions, specifically Zn2+, Co2+, Fe2+ and Cu2+. However, Zn2+ is effective in five-fold lower molar concentrations (1-10(-4) M) than the other ions. Furthermore, Zn2+ was the only ion tested able to prevent and reverse the inhibition of collagenase by EDTA in the presence of excess Ca2+. Atomic absorption analysis of purified collagenase for Zn2+ showed that Zn2+ was present in the enzyme preparations, and that the metal co-purifies with collagenase during column chromatography.", "contents": "Evidence for mammalian collagenases as zinc ion metalloenzymes. Collagenases (EC 3.4.24.3) from human skin, rat skin and rat uterus were inhibited by the chelating agents EDTA, 1,10-phenanthroline and tetraethylene pentamine in the presence of excess Ca2+, suggesting that a second metal ion participates in the activity of the enzyme. Collagenase inhibition by 1,10-phenanthroline could be both prevented and reversed by a number of transition metal ions, specifically Zn2+, Co2+, Fe2+ and Cu2+. However, Zn2+ is effective in five-fold lower molar concentrations (1-10(-4) M) than the other ions. Furthermore, Zn2+ was the only ion tested able to prevent and reverse the inhibition of collagenase by EDTA in the presence of excess Ca2+. Atomic absorption analysis of purified collagenase for Zn2+ showed that Zn2+ was present in the enzyme preparations, and that the metal co-purifies with collagenase during column chromatography."}
{"id": "PMID:199266", "title": "Protocatechuate 3,4-dioxygenase. Inhibitor studies and mechanistic implications.", "content": "Protocatechuate 3,4-dioxygenase (EC 1.13.11.3) from Pseudomonas aeruginosa catalyzes the cleavage of 3,4-dihydroxybenzoate (protocatechuate) into beta-carboxy-cis,cis-muconate. The inhibition constants, Ki, of a series of substrate analogues were measured in order to assess the relative importance of the various functional groups on the substrate. Though important for binding, the carboxylate group is not essential for activity. Compounds with para hydroxy groups are better inhibitors than their meta isomers. Our studies of the enzyme-inhibitor complexes indicate that the 4-OH group of the substrate binds to the active-site iron. Taken together, M\u00f6ssbauer, EPR, and kinetic data suggest a mechanism where substrate reaction with oxygen is preceded by metal activation of substrate.", "contents": "Protocatechuate 3,4-dioxygenase. Inhibitor studies and mechanistic implications. Protocatechuate 3,4-dioxygenase (EC 1.13.11.3) from Pseudomonas aeruginosa catalyzes the cleavage of 3,4-dihydroxybenzoate (protocatechuate) into beta-carboxy-cis,cis-muconate. The inhibition constants, Ki, of a series of substrate analogues were measured in order to assess the relative importance of the various functional groups on the substrate. Though important for binding, the carboxylate group is not essential for activity. Compounds with para hydroxy groups are better inhibitors than their meta isomers. Our studies of the enzyme-inhibitor complexes indicate that the 4-OH group of the substrate binds to the active-site iron. Taken together, M\u00f6ssbauer, EPR, and kinetic data suggest a mechanism where substrate reaction with oxygen is preceded by metal activation of substrate."}
{"id": "PMID:199269", "title": "Concentration of lipoproteins containing apolipoprotein B in human peripheral lymph.", "content": "The concentration of apolipoprotein B (apoB) in human serum and peripheral lymph was measured by quantitative immunoelectrophoresis with anti-serum to human low-density lipoprotein. In four normal and six hyperlipidaemic subjects, total lymph apob/ml was 5-10% of total serum apoB/ml in the same subject. These ratios were equivalent to lymph apob concentrations of 60-120 microgram/ml. When the assays were carried out under conditions in which unmasking of immunoreactive sites on lymph and serum apoB was assumed to be maximal (delipidation with Nonidet P40), the lymph/serum apoB concentration ratios in three normal subjects were similar to those obtained with untreated lymph and serum.", "contents": "Concentration of lipoproteins containing apolipoprotein B in human peripheral lymph. The concentration of apolipoprotein B (apoB) in human serum and peripheral lymph was measured by quantitative immunoelectrophoresis with anti-serum to human low-density lipoprotein. In four normal and six hyperlipidaemic subjects, total lymph apob/ml was 5-10% of total serum apoB/ml in the same subject. These ratios were equivalent to lymph apob concentrations of 60-120 microgram/ml. When the assays were carried out under conditions in which unmasking of immunoreactive sites on lymph and serum apoB was assumed to be maximal (delipidation with Nonidet P40), the lymph/serum apoB concentration ratios in three normal subjects were similar to those obtained with untreated lymph and serum."}
{"id": "PMID:199270", "title": "Theta-toxin of Clostridium perfringens. I. Purification and some properties.", "content": "Theta-Toxin, an oxygen-labile hemolysin produced by Clostridium perfringens, was purified 3300 fold from culture filtrate by successive chromatography on DEAE-Sephadex A-50 and Sephadex G-150. The purified toxin gave two distinct bands in disc electrophoresis, while the same material, after mild reduction with dithiothreitol, yielded a single band, indicating that the purified theta-toxin contained, as well as a reduced, active form, an oxidized, inactive form of toxin. These two forms of the toxin had a similar, if not identical molecular size. The purified preparation gave a single band in a sodium dodecyl sulfate polyacrylamide gel electrophoresis and formed a single precipitin line with National Standard gas gangrene (C. perfringens) antitoxin. By sodium dodecyl sulfate polyacrylamide gel electrophoresis, the molecular weight of theta-toxin was estimated to be 51 000, the value being in exact accordance with that obtained by amino acid analysis. The amino acid composition of theta-toxin was very close to that of cereolysin, an oxygen-labile hemolysin produced by Bacillus cereus. The amino-terminal residue of theta-toxin was lysine as determined by the Dansyl method.", "contents": "Theta-toxin of Clostridium perfringens. I. Purification and some properties. Theta-Toxin, an oxygen-labile hemolysin produced by Clostridium perfringens, was purified 3300 fold from culture filtrate by successive chromatography on DEAE-Sephadex A-50 and Sephadex G-150. The purified toxin gave two distinct bands in disc electrophoresis, while the same material, after mild reduction with dithiothreitol, yielded a single band, indicating that the purified theta-toxin contained, as well as a reduced, active form, an oxidized, inactive form of toxin. These two forms of the toxin had a similar, if not identical molecular size. The purified preparation gave a single band in a sodium dodecyl sulfate polyacrylamide gel electrophoresis and formed a single precipitin line with National Standard gas gangrene (C. perfringens) antitoxin. By sodium dodecyl sulfate polyacrylamide gel electrophoresis, the molecular weight of theta-toxin was estimated to be 51 000, the value being in exact accordance with that obtained by amino acid analysis. The amino acid composition of theta-toxin was very close to that of cereolysin, an oxygen-labile hemolysin produced by Bacillus cereus. The amino-terminal residue of theta-toxin was lysine as determined by the Dansyl method."}
{"id": "PMID:199271", "title": "Thermodynamic characterization of partially denatured states in the denaturation process of bovine alpha-lactalbumin by inorganic denaturants.", "content": "In an attempt to understand the specific effect of inorganic protein denaturants, lithium cation and perchlorate anion, upon the molecular conformation of bovine alpha-lactalbumin and to characterize the denatured states of the protein and the denaturation processes, themodynamic studies on the reversible unfolding of the protein in the presence of lithium chloride, lithium perchlorate and sodium perchlorate were made by means of circular dichroism and ultraviolet absorption measurements. The denaturation reaction caused by lithium chloride was found to take place in a three-state type, while that caused by the two perchlorates in a two-state type. The latter produces the same denatured state as the acid does on the protein, the state where the helical structures remain unchanged. The former produces two kinds of the denatured state, one being a less unfolded state than the acid denatured one and the other a fully unfolded state which is identical with the finally denatured state induced by organic denaturants such as guanidinium chloride, guanidinium thiocyanate and urea.", "contents": "Thermodynamic characterization of partially denatured states in the denaturation process of bovine alpha-lactalbumin by inorganic denaturants. In an attempt to understand the specific effect of inorganic protein denaturants, lithium cation and perchlorate anion, upon the molecular conformation of bovine alpha-lactalbumin and to characterize the denatured states of the protein and the denaturation processes, themodynamic studies on the reversible unfolding of the protein in the presence of lithium chloride, lithium perchlorate and sodium perchlorate were made by means of circular dichroism and ultraviolet absorption measurements. The denaturation reaction caused by lithium chloride was found to take place in a three-state type, while that caused by the two perchlorates in a two-state type. The latter produces the same denatured state as the acid does on the protein, the state where the helical structures remain unchanged. The former produces two kinds of the denatured state, one being a less unfolded state than the acid denatured one and the other a fully unfolded state which is identical with the finally denatured state induced by organic denaturants such as guanidinium chloride, guanidinium thiocyanate and urea."}
{"id": "PMID:199272", "title": "Haemoglobin North Shore, beta134 Val replaced by Glu, a new unstable haemoglobin.", "content": "A new mildly unstable haemoglobin, Hb North Shore (beta134 Val replaced by Glu) is described. It was found in a 4th generation Australian of Anglo-Celtic origin with a mild microcytic anaemia. The charge change involved is partially obscured as evidenced by the electrophoretic mobility of the native haemoglobin. The structural studies illustrate the usefulness of Staphylococcus aureus strain V8 protease as a specific cleavage enzyme at glutamyl residues.", "contents": "Haemoglobin North Shore, beta134 Val replaced by Glu, a new unstable haemoglobin. A new mildly unstable haemoglobin, Hb North Shore (beta134 Val replaced by Glu) is described. It was found in a 4th generation Australian of Anglo-Celtic origin with a mild microcytic anaemia. The charge change involved is partially obscured as evidenced by the electrophoretic mobility of the native haemoglobin. The structural studies illustrate the usefulness of Staphylococcus aureus strain V8 protease as a specific cleavage enzyme at glutamyl residues."}
{"id": "PMID:199273", "title": "M\u00f6ssbauer studies of cytochrome c' from Rhodospirillum rubrum.", "content": "Cytochrome c' from Rhodospirillum rubrum has been investigated in the ferric form with M\u00f6ssbauer and EPR spectroscopy. In the pH range from 6 to 9.5, three species are observed which belong to two pH-dependent equilibria with pK values near 6 and 8.5. The pK = 6 transition is resolved only with high-field M\u00f6ssbauer spectroscopy. For the three species we have determined the zero-field splitting parameters and the hyperfine coupling constants. The data were fitted to a spin Hamiltonian which takes into account a weak mixing of excited S = 3/2 states into the sextet ground manifold. The low temperature spectra clearly show that the quadruple coupling constant deltaEQ is positive for ferricytochrome c' and thus in accord with all other high-spin ferric heme proteins.", "contents": "M\u00f6ssbauer studies of cytochrome c' from Rhodospirillum rubrum. Cytochrome c' from Rhodospirillum rubrum has been investigated in the ferric form with M\u00f6ssbauer and EPR spectroscopy. In the pH range from 6 to 9.5, three species are observed which belong to two pH-dependent equilibria with pK values near 6 and 8.5. The pK = 6 transition is resolved only with high-field M\u00f6ssbauer spectroscopy. For the three species we have determined the zero-field splitting parameters and the hyperfine coupling constants. The data were fitted to a spin Hamiltonian which takes into account a weak mixing of excited S = 3/2 states into the sextet ground manifold. The low temperature spectra clearly show that the quadruple coupling constant deltaEQ is positive for ferricytochrome c' and thus in accord with all other high-spin ferric heme proteins."}
{"id": "PMID:199274", "title": "Phosphodiesterase from cultured tobacco cells. Physical and chemical properties.", "content": "Phosphodiesterase isolated from suspension cultures of tobacco cells showed high affinity for concanavalin A-Sepharose and gave single superimposed bands of protein and carbohydrates on disc gel electrophoresis, suggesting that it is a glycoprotein. It contains 14% carbohydrate by weight, and has relatively high contents of basic and aromatic amino acids. Its isoelectric point is at pH 8.8, and the molecular weight of its subunits was estimated as 72 000 from a plot of the retardation coefficient on sodium dodecyl sulfate gel electrophoresis versus the molecular weight. The enzyme was catalytically active in an immobilized state on a concanavalin A-Sepharose column.", "contents": "Phosphodiesterase from cultured tobacco cells. Physical and chemical properties. Phosphodiesterase isolated from suspension cultures of tobacco cells showed high affinity for concanavalin A-Sepharose and gave single superimposed bands of protein and carbohydrates on disc gel electrophoresis, suggesting that it is a glycoprotein. It contains 14% carbohydrate by weight, and has relatively high contents of basic and aromatic amino acids. Its isoelectric point is at pH 8.8, and the molecular weight of its subunits was estimated as 72 000 from a plot of the retardation coefficient on sodium dodecyl sulfate gel electrophoresis versus the molecular weight. The enzyme was catalytically active in an immobilized state on a concanavalin A-Sepharose column."}
{"id": "PMID:199275", "title": "Effects of human chorionic gonadotropin and N6,O2'-dibutyryladenosine 3' ,5'-monophosphate on phosphofructokinase activity in isolated rat testis.", "content": "Phosphofructokinase activity in rat testis is elevated by treatment in vitro with human chorionic godadotropin or N6,O2'-dibutyryladenosine 3' ,5'-monophosphate. Puromycin or actinomycin D suppresses the effect of the gonadotropin but does not affect the enzyme increase induced by the cyclic nucleotide. The possible cause for the divergent action of the two stimulatory agents are discussed.", "contents": "Effects of human chorionic gonadotropin and N6,O2'-dibutyryladenosine 3' ,5'-monophosphate on phosphofructokinase activity in isolated rat testis. Phosphofructokinase activity in rat testis is elevated by treatment in vitro with human chorionic godadotropin or N6,O2'-dibutyryladenosine 3' ,5'-monophosphate. Puromycin or actinomycin D suppresses the effect of the gonadotropin but does not affect the enzyme increase induced by the cyclic nucleotide. The possible cause for the divergent action of the two stimulatory agents are discussed."}
{"id": "PMID:199277", "title": "[Formation of free radicals during photooxidation of bacterioviridin in its monomeric and aggregated state].", "content": "ESR study of photooxidation of bacterioviridin in polar and non-polar organic solvents containing monomeric and aggregated forms of the pigment was carried out. Light-indiced formation of free radicals was shown to proceed during photooxidation of bacterioviridin with oxygen. These free radicals were similar by the ESR-signal parameters (G-factor value and the line width) to the cation-radicals initiated during photooxidation of the pigment with p-benzoquinone and at the same time differing in kinetics and temperature relationship. A small yield of radical products in the presence of oxygen is observed in non-polar solvents where bacterioviridin forms the aggregated forms with the absorption maxima of 680 and 720 nm. The study of the kinetics of photoformation of radicals within the temperature range +20-- --110 degrees allowed to reveal different stages corresponding to the oxidation of the long wave and short wave forms of bacterioviridin, photooxidation of the long wave aggregated form being the first stage of photoprocess. It is concluded that aggregations contributs to the stabilization of the primary reversible products of bacterioviridin photooxidation having the nature of free radicals.", "contents": "[Formation of free radicals during photooxidation of bacterioviridin in its monomeric and aggregated state]. ESR study of photooxidation of bacterioviridin in polar and non-polar organic solvents containing monomeric and aggregated forms of the pigment was carried out. Light-indiced formation of free radicals was shown to proceed during photooxidation of bacterioviridin with oxygen. These free radicals were similar by the ESR-signal parameters (G-factor value and the line width) to the cation-radicals initiated during photooxidation of the pigment with p-benzoquinone and at the same time differing in kinetics and temperature relationship. A small yield of radical products in the presence of oxygen is observed in non-polar solvents where bacterioviridin forms the aggregated forms with the absorption maxima of 680 and 720 nm. The study of the kinetics of photoformation of radicals within the temperature range +20-- --110 degrees allowed to reveal different stages corresponding to the oxidation of the long wave and short wave forms of bacterioviridin, photooxidation of the long wave aggregated form being the first stage of photoprocess. It is concluded that aggregations contributs to the stabilization of the primary reversible products of bacterioviridin photooxidation having the nature of free radicals."}
{"id": "PMID:199278", "title": "[Solubility of adenosine in concentrated salt solutions].", "content": "The solubility of adenosine has been measured in concentrated neutral salt solutions of NaClO4 (salt-destabilizer) and Na2SO4 (salt-stabilizer) as a function of salt concentration and temperature. The thermodynamic functions of adenosine transfer from water to salt solutions have been estimated. The values of delta Ftr, delta Htr, delta Str adenosine transfer in NaClO4 solutions are negative, in Na2SO4--positive. The results are considered in connection with the mechanism of high concentrations of salt action on DNA in the water solutions.", "contents": "[Solubility of adenosine in concentrated salt solutions]. The solubility of adenosine has been measured in concentrated neutral salt solutions of NaClO4 (salt-destabilizer) and Na2SO4 (salt-stabilizer) as a function of salt concentration and temperature. The thermodynamic functions of adenosine transfer from water to salt solutions have been estimated. The values of delta Ftr, delta Htr, delta Str adenosine transfer in NaClO4 solutions are negative, in Na2SO4--positive. The results are considered in connection with the mechanism of high concentrations of salt action on DNA in the water solutions."}
{"id": "PMID:199280", "title": "[Study of electron transport in the photosynthetic systems of higher plants by the EPR method. V. Interaction of paramagnetic prob I(12,3) with the membranes of bean chloroplasts].", "content": "Lipid-soluble paramagnetic proble I(12,3) was subjected to partially reversible photoinduced redox transformations while interacting with the electron-transport chains of chloroplasts. Incorporation of I(12,3) into the chloroplast membrane does not affect the kinetic characteristics of the EPR I signal (from P700+). The parameters of the EPR spectrum from I(12,3) are not changed under illumination, however, they are sensitive to temperature and different additions (Mg2+, ATP, atebrin).", "contents": "[Study of electron transport in the photosynthetic systems of higher plants by the EPR method. V. Interaction of paramagnetic prob I(12,3) with the membranes of bean chloroplasts]. Lipid-soluble paramagnetic proble I(12,3) was subjected to partially reversible photoinduced redox transformations while interacting with the electron-transport chains of chloroplasts. Incorporation of I(12,3) into the chloroplast membrane does not affect the kinetic characteristics of the EPR I signal (from P700+). The parameters of the EPR spectrum from I(12,3) are not changed under illumination, however, they are sensitive to temperature and different additions (Mg2+, ATP, atebrin)."}
{"id": "PMID:199284", "title": "[Different cooperativity of some oxidoreductases to specialized and nonspecialized regulators].", "content": "The activation of 2 different mouse liver enzymes: cytozolic disulfide reductase (DSR) and mitochondrial NAD-isocitrate dehydrogenase (ICDH), by catecholamines and especially by 3',5'-AMP is characterized by negative cooperativity; substrate (both enzymes), protamine and EDTA (DSR) produce the positive cooperativity type of activation; DSR activation by isopropyl noradrenaline and serotonine is characterized by hyperbolic kinetics. Consequently, one and the same enzyme can combine positive cooperativity to non-specialized regulators (substrate, protamine, EDTA) with negative cooperativity to specialized regulators (3',5'-AMP, catecholamines). The systems, switching on by catecholamines and 3',5'-AMP, are oligomeric, and the degree and even the type of cooperativity can modify depending on the kind of catecholamine. The negative cooperativity is revealed in literature for many effects of catecholamines and 3',5'-AMP. Probably, it guarantees the broad range of regulations. Dose effect curves for 3',5'-AMP, catecholamines and other hormones should be analyzed on the basis of allosteric protein kinetics. A simple nomogram is given to estimate nH less than 1.", "contents": "[Different cooperativity of some oxidoreductases to specialized and nonspecialized regulators]. The activation of 2 different mouse liver enzymes: cytozolic disulfide reductase (DSR) and mitochondrial NAD-isocitrate dehydrogenase (ICDH), by catecholamines and especially by 3',5'-AMP is characterized by negative cooperativity; substrate (both enzymes), protamine and EDTA (DSR) produce the positive cooperativity type of activation; DSR activation by isopropyl noradrenaline and serotonine is characterized by hyperbolic kinetics. Consequently, one and the same enzyme can combine positive cooperativity to non-specialized regulators (substrate, protamine, EDTA) with negative cooperativity to specialized regulators (3',5'-AMP, catecholamines). The systems, switching on by catecholamines and 3',5'-AMP, are oligomeric, and the degree and even the type of cooperativity can modify depending on the kind of catecholamine. The negative cooperativity is revealed in literature for many effects of catecholamines and 3',5'-AMP. Probably, it guarantees the broad range of regulations. Dose effect curves for 3',5'-AMP, catecholamines and other hormones should be analyzed on the basis of allosteric protein kinetics. A simple nomogram is given to estimate nH less than 1."}
{"id": "PMID:199285", "title": "[Preparative isolation and some properties of SV40 T-antigen].", "content": "SV40 T-antigen was isolated from hamster tumors and purified about 1600-fold by the procedure including successive ammonium sulfate precipitation, chromatography on DEAE-cellulose, preparative polyacrylamide gel electrophoresis and elimination of the bulk of contaminating cell proteins by the interaction with antibodies to the tissues of normal hamsters. The resulting preparation was not quite homogenous being contaminated with some of cell proteins left. T-antigen in the tumor extract was revealed at least in three distinct forms with molecular weight of 100 000, 200 000, and 400 000. It is proposed that these forms correspond to mono-, di-, and tetramers of the basal protein of T-antigen, although the alternative explanation, the existence of complex of T-antigen with cell proteins, cannot be ruled out.", "contents": "[Preparative isolation and some properties of SV40 T-antigen]. SV40 T-antigen was isolated from hamster tumors and purified about 1600-fold by the procedure including successive ammonium sulfate precipitation, chromatography on DEAE-cellulose, preparative polyacrylamide gel electrophoresis and elimination of the bulk of contaminating cell proteins by the interaction with antibodies to the tissues of normal hamsters. The resulting preparation was not quite homogenous being contaminated with some of cell proteins left. T-antigen in the tumor extract was revealed at least in three distinct forms with molecular weight of 100 000, 200 000, and 400 000. It is proposed that these forms correspond to mono-, di-, and tetramers of the basal protein of T-antigen, although the alternative explanation, the existence of complex of T-antigen with cell proteins, cannot be ruled out."}
{"id": "PMID:199281", "title": "[Role of superoxide anion-radicals and superoxide dismutase in the lipid photoperoxidation reactions of isolated chloroplasts].", "content": "Exogenous superoxide dismutase (SOD, erythrocuprein) inhibits the chlorophyll bleaching and photoperoxidation of polyunsaturated lipids in pea isolated chloroplasts. As SOD did not produce this effect in tris-HCl buffer, it is suggested that peroxidation is mediated by the OH radicals which may appear in illuminated chloroplasts with the participation of superoxide radicals and hydrogen peroxide. The physiological role of SOD is discussed in relation to the stability of cells photosynthesizing organisms towards light and oxygen effect.", "contents": "[Role of superoxide anion-radicals and superoxide dismutase in the lipid photoperoxidation reactions of isolated chloroplasts]. Exogenous superoxide dismutase (SOD, erythrocuprein) inhibits the chlorophyll bleaching and photoperoxidation of polyunsaturated lipids in pea isolated chloroplasts. As SOD did not produce this effect in tris-HCl buffer, it is suggested that peroxidation is mediated by the OH radicals which may appear in illuminated chloroplasts with the participation of superoxide radicals and hydrogen peroxide. The physiological role of SOD is discussed in relation to the stability of cells photosynthesizing organisms towards light and oxygen effect."}
{"id": "PMID:199286", "title": "[Effect of NAD recirculation on the mechanism of ATP stabilization in cytoplasm. Mathematical models].", "content": "A mathematical model of the glycolytic system with the cytoplasmic coenzymes NAD+ and NADH as essential variables is proposed. It has been shown that any increase in the steady-state concentration of NADH will reduce the range of activity of the \"generalized\" ATPase, wherein the level of ATP is stabilized. Such a reduction in the range of ATP stabilization may be caused by an increasing rate of the pyruvate loss into non-glycolytic pathways, in particular, into mitochondria. This effect may be compensated by increasing oxidation of NADH by the dehydrogenases of H+-transferring cytosol-mitochondrial shuttles (malate-aspartate or alpha-glycerophosphate). The properties of the complete model were compared with those of its simplified version, which takes account only of the phosphotransferase reactions of glycolysis. The effects of various factors, which do not alter the level of NADH in the system, may be studied within the scope of the simplified model.", "contents": "[Effect of NAD recirculation on the mechanism of ATP stabilization in cytoplasm. Mathematical models]. A mathematical model of the glycolytic system with the cytoplasmic coenzymes NAD+ and NADH as essential variables is proposed. It has been shown that any increase in the steady-state concentration of NADH will reduce the range of activity of the \"generalized\" ATPase, wherein the level of ATP is stabilized. Such a reduction in the range of ATP stabilization may be caused by an increasing rate of the pyruvate loss into non-glycolytic pathways, in particular, into mitochondria. This effect may be compensated by increasing oxidation of NADH by the dehydrogenases of H+-transferring cytosol-mitochondrial shuttles (malate-aspartate or alpha-glycerophosphate). The properties of the complete model were compared with those of its simplified version, which takes account only of the phosphotransferase reactions of glycolysis. The effects of various factors, which do not alter the level of NADH in the system, may be studied within the scope of the simplified model."}
{"id": "PMID:199282", "title": "[Factors influencing formation of dinitrosyl complexes of non-heme iron in the organs of animals in vivo].", "content": "The formation of paramagnetic non-haem iron dinitrozyl complexes (2,03 complexes) in mouse liver has been detected, when these animals were exposed to a diet with high content of nitrite or nitrite and iron salt. These complexes appeared after 3-5 days and their content was kept at the same level during a month. The 2,03 complexes content in mouse liver was 3 times higher for mice which were exposed to the diet with nitrite and iron salt than for those on the diet only with nitrite. While the liver preparations of experimental mice were treated with NO in vitro the 2,03 complexes content increased in the liver and reached the same level for all experimental mice. It has been supposed that the 2.03 complexes formation was limited in mouse liver in vivo, both by NO production in the liver and by the content of the more labile form of non-haem iron, which was primarily incorporated into the complexes.", "contents": "[Factors influencing formation of dinitrosyl complexes of non-heme iron in the organs of animals in vivo]. The formation of paramagnetic non-haem iron dinitrozyl complexes (2,03 complexes) in mouse liver has been detected, when these animals were exposed to a diet with high content of nitrite or nitrite and iron salt. These complexes appeared after 3-5 days and their content was kept at the same level during a month. The 2,03 complexes content in mouse liver was 3 times higher for mice which were exposed to the diet with nitrite and iron salt than for those on the diet only with nitrite. While the liver preparations of experimental mice were treated with NO in vitro the 2,03 complexes content increased in the liver and reached the same level for all experimental mice. It has been supposed that the 2.03 complexes formation was limited in mouse liver in vivo, both by NO production in the liver and by the content of the more labile form of non-haem iron, which was primarily incorporated into the complexes."}
{"id": "PMID:199287", "title": "[Polyphosphate kinase activity in yeast vacuoles].", "content": "The enzyme polyphosphate kinase (ATP: Polyphosphate phosphotransferase EC 2.7.4.1) relating to the class of transferases was detected in the vacuoles of Saccharomyces carlsbergensis yeast. The direct ATP: Polyphosphate phosphotransferase reaction resulting in the synthesis of polyphosphates from ATP was shown to occur mainly in vacuoles. The localization of the reverse polyphosphate: ADP phosphatransferase reaction was not established in any of the subcellular yeast fractions studied. The activity of the direct reaction in the yeast protoplasts makes up about 1% of the reverse one, but in vacuoles it is significantly higher and makes up to 19%. Under activation of biochemical processes involved in the production of cell wall components by protoplasts, vacuolar polyphosphates work mainly in the direction of ATP synthesis at the expense of polyphosphates accumulated in vacuoles.", "contents": "[Polyphosphate kinase activity in yeast vacuoles]. The enzyme polyphosphate kinase (ATP: Polyphosphate phosphotransferase EC 2.7.4.1) relating to the class of transferases was detected in the vacuoles of Saccharomyces carlsbergensis yeast. The direct ATP: Polyphosphate phosphotransferase reaction resulting in the synthesis of polyphosphates from ATP was shown to occur mainly in vacuoles. The localization of the reverse polyphosphate: ADP phosphatransferase reaction was not established in any of the subcellular yeast fractions studied. The activity of the direct reaction in the yeast protoplasts makes up about 1% of the reverse one, but in vacuoles it is significantly higher and makes up to 19%. Under activation of biochemical processes involved in the production of cell wall components by protoplasts, vacuolar polyphosphates work mainly in the direction of ATP synthesis at the expense of polyphosphates accumulated in vacuoles."}
{"id": "PMID:199283", "title": "[Use of spin labels for studying the association of adenosine, adenosine-5'-mono-, di- and triphosphate in aqueous solutions].", "content": "Possibility of spin label studies as a method of investigation of different molecular associations is considered with adenosine, adenosine-5'-mono, di- and triphosphate as examples. The proposed method is based on dependence of the parameters of spin-labelled derivatives ESR-spectra on concentration of corresponding unlabelled compounds. Being highly sensitive the method takes the advantage of obtaining not only thermodynamic characteristics of association but dynamic parameters of molecular mobility of the associates as well. It is shown by this method that base-phosphate interaction participates in nucleotide association, together with the stacking interaction.", "contents": "[Use of spin labels for studying the association of adenosine, adenosine-5'-mono-, di- and triphosphate in aqueous solutions]. Possibility of spin label studies as a method of investigation of different molecular associations is considered with adenosine, adenosine-5'-mono, di- and triphosphate as examples. The proposed method is based on dependence of the parameters of spin-labelled derivatives ESR-spectra on concentration of corresponding unlabelled compounds. Being highly sensitive the method takes the advantage of obtaining not only thermodynamic characteristics of association but dynamic parameters of molecular mobility of the associates as well. It is shown by this method that base-phosphate interaction participates in nucleotide association, together with the stacking interaction."}
{"id": "PMID:199288", "title": "[Activities of some yeast flavogenic enzymes in situ].", "content": "Effects of digitonin, dimethylsulfoxide and protamine sulfate on yeast Pichia guilliermondii were studied in order to produce cells with increased permeability and possessing the GTP-cyclohydrolase, riboflavinsynthetase and riboflavinkinase activities. The digitonin-treated cells exhibited a higher cyclohydrolase activity than the cell-free extracts; the activities of riboflavinsynthetase and riboflavinkinase in the cells and cell-free extracts were found to be similar. Treatment of cells with dimethylsulfoxide proved to be most effective to determine the activity of GTP-cyclohydrolase and also helpful to determine that of riboflavinsynthetase. Protamine sulfate had no effect on the cells of P. guilliermondii. The methods developed were used to determine the activities of GTP-cyclohydrolase, riboflavinsynthetase and riboflavinkinase in the cells of flavinogenic (P. guiller-mondii, Torulopsis candida) and non-flavinogenic (Candida utilis, Candida pulcherrima) yeasts grown in iron-rich and iron-deficient media. Derepression of riboflavinsynthetase and GTP-cyclohydrolase syntheses under conditions of Fe deficiency in the flavinogenic yeast cells confirmed previously made assumptions.", "contents": "[Activities of some yeast flavogenic enzymes in situ]. Effects of digitonin, dimethylsulfoxide and protamine sulfate on yeast Pichia guilliermondii were studied in order to produce cells with increased permeability and possessing the GTP-cyclohydrolase, riboflavinsynthetase and riboflavinkinase activities. The digitonin-treated cells exhibited a higher cyclohydrolase activity than the cell-free extracts; the activities of riboflavinsynthetase and riboflavinkinase in the cells and cell-free extracts were found to be similar. Treatment of cells with dimethylsulfoxide proved to be most effective to determine the activity of GTP-cyclohydrolase and also helpful to determine that of riboflavinsynthetase. Protamine sulfate had no effect on the cells of P. guilliermondii. The methods developed were used to determine the activities of GTP-cyclohydrolase, riboflavinsynthetase and riboflavinkinase in the cells of flavinogenic (P. guiller-mondii, Torulopsis candida) and non-flavinogenic (Candida utilis, Candida pulcherrima) yeasts grown in iron-rich and iron-deficient media. Derepression of riboflavinsynthetase and GTP-cyclohydrolase syntheses under conditions of Fe deficiency in the flavinogenic yeast cells confirmed previously made assumptions."}
{"id": "PMID:199290", "title": "[Effect of aminazin on changes in the electrical activity of the cerebral cortex under the influence of the toxin C1. perfringens type A].", "content": "Experiments on cats revealed that injection of chlorpromazine (3 mg/kg of body weight, intramuscular) one hour prior to the Cl. perfingens toxin type A injection prevented the appearance of desynchronization of the electrical activity of the cerebral cortex usually observed during the first phase of intoxication. Chlorpromazine injection postpones the appearance of the electrical activity depression phase during the second phase and prolonged the animals' life span from 1.5 to 2 times. The effect of chlorpromazine was apparently connected with the block of the adrenergic structures of the brain stem reticular formation.", "contents": "[Effect of aminazin on changes in the electrical activity of the cerebral cortex under the influence of the toxin C1. perfringens type A]. Experiments on cats revealed that injection of chlorpromazine (3 mg/kg of body weight, intramuscular) one hour prior to the Cl. perfingens toxin type A injection prevented the appearance of desynchronization of the electrical activity of the cerebral cortex usually observed during the first phase of intoxication. Chlorpromazine injection postpones the appearance of the electrical activity depression phase during the second phase and prolonged the animals' life span from 1.5 to 2 times. The effect of chlorpromazine was apparently connected with the block of the adrenergic structures of the brain stem reticular formation."}
{"id": "PMID:199291", "title": "[Effect of epidermal chalones on the growth of transplantable tumors].", "content": "The ethanolic extract of rat skin contains epidermal G1- and G2-chalones which having been added to cell suspension of transplantable squamous-cell cornified carcinoma of mice cervix, inhibits its growth in recipients by 72,6 per cent. The same extract failed to inhibit the growth of transplantable mouse tumours of other histogenesis (hepatoma 22a, leukemia L-1210 and sarcoma 180). When added to cell suspension of transplantable carcinoma of mouse skin which had been anaplized during a long period of transplantation (over 10 years) this extract inhibits its growth by 39,2 per cent only.", "contents": "[Effect of epidermal chalones on the growth of transplantable tumors]. The ethanolic extract of rat skin contains epidermal G1- and G2-chalones which having been added to cell suspension of transplantable squamous-cell cornified carcinoma of mice cervix, inhibits its growth in recipients by 72,6 per cent. The same extract failed to inhibit the growth of transplantable mouse tumours of other histogenesis (hepatoma 22a, leukemia L-1210 and sarcoma 180). When added to cell suspension of transplantable carcinoma of mouse skin which had been anaplized during a long period of transplantation (over 10 years) this extract inhibits its growth by 39,2 per cent only."}
{"id": "PMID:199292", "title": "[Concentration and metabolism of cyclic AMP during the early stages of hepatoma 22a growth].", "content": "Intracellular levels of cyclic AMP (cAMP), adenylate cyclase, and cAMP-phosphodiesterase activities at lag-period, exponential and stationary growth phases of hepatoma 22a were determined. It was shown that the transition of tumour cells from the lag-period to the exponential phase of growth was accompanied by the two-fold decrease of intracellular cAMP level on account of drastic activation of cAMP phosphodiesterase. Subsequently the cAMP level lowered more slowly until the cells entered the stationary phase of growth. In view of the fact that the adenylate cyclase activity failed to change at different growth phases of hepatoma 22a, it seems very proballe that the rise of cAMP phosphodiesterase activity could be a signal for the exit of tumour cells from the lag-period and their entrance into the mitotic cycle.", "contents": "[Concentration and metabolism of cyclic AMP during the early stages of hepatoma 22a growth]. Intracellular levels of cyclic AMP (cAMP), adenylate cyclase, and cAMP-phosphodiesterase activities at lag-period, exponential and stationary growth phases of hepatoma 22a were determined. It was shown that the transition of tumour cells from the lag-period to the exponential phase of growth was accompanied by the two-fold decrease of intracellular cAMP level on account of drastic activation of cAMP phosphodiesterase. Subsequently the cAMP level lowered more slowly until the cells entered the stationary phase of growth. In view of the fact that the adenylate cyclase activity failed to change at different growth phases of hepatoma 22a, it seems very proballe that the rise of cAMP phosphodiesterase activity could be a signal for the exit of tumour cells from the lag-period and their entrance into the mitotic cycle."}
{"id": "PMID:199293", "title": "[Mechanism of disorders in energy formation in acute hepatic ischemia].", "content": "Respiration of hepatic mitochondria of rats after addition of ischemic toxin to the incubation medium was compared with respiration of mitochondria isolated from an ischemic rat liver. Its change could be prevented in both cases by the preliminary administration of dithiotreitol and could be decreased by the subsequent addition of cytochrome C or dithiotreitol into the incubation medium. Similarity of the mechanisms of disturbed energy formation in vivo and in vitro is supposed.", "contents": "[Mechanism of disorders in energy formation in acute hepatic ischemia]. Respiration of hepatic mitochondria of rats after addition of ischemic toxin to the incubation medium was compared with respiration of mitochondria isolated from an ischemic rat liver. Its change could be prevented in both cases by the preliminary administration of dithiotreitol and could be decreased by the subsequent addition of cytochrome C or dithiotreitol into the incubation medium. Similarity of the mechanisms of disturbed energy formation in vivo and in vitro is supposed."}
{"id": "PMID:199294", "title": "[Effect of benz(a)pyrene on a monolayer culture of normal and malignant mouse liver cells].", "content": "Both the cells of monolayer culture of mouse embryonic liver and that of highly malignant hepatoma 22A transplanted for 20 years actively metabolized the carcinogenic hydrocarbon benz(a)pyrene and were highly sensitive to iits toxic action. Since hepatic tissue was resistant in vivo to carcinogenic carbohydrates it is suggested that the resistance depended on factors acting at the organ or the organism but not as the cellular level. The mechanism of retention of hepatoma 22A sensitivity to the toxic action of benz(a)pyrene is also discussed.", "contents": "[Effect of benz(a)pyrene on a monolayer culture of normal and malignant mouse liver cells]. Both the cells of monolayer culture of mouse embryonic liver and that of highly malignant hepatoma 22A transplanted for 20 years actively metabolized the carcinogenic hydrocarbon benz(a)pyrene and were highly sensitive to iits toxic action. Since hepatic tissue was resistant in vivo to carcinogenic carbohydrates it is suggested that the resistance depended on factors acting at the organ or the organism but not as the cellular level. The mechanism of retention of hepatoma 22A sensitivity to the toxic action of benz(a)pyrene is also discussed."}
{"id": "PMID:199295", "title": "[Pathologic anatomy of experimental diseases of small laboratory animals caused by encephalomyocarditis virus (strain EMK-70)].", "content": "The results of pathomorphological investigation of the disease in small laboratory animals experimentally induced by the EMC-70 strain of encephalomyocarditis virus isolated from monkeys are presented. Irrespective of the mode of virus injection, the newborn and juvenile mice developed some lesions in the brown fat, transverse-striated muscles, as well as in the brain and heart. In guinea pigs the changes were characterized by the development of severe myocarditis and encephalitis accompanied by viral antigen accumulation. The disease induced by the EMC-70 strain could not be differentiated from the Coxsackie infection by the pathomorphological data. This fact should be taken into consideration in solving some problems pertinent to pathoanatomical diagnosis of viral diseases.", "contents": "[Pathologic anatomy of experimental diseases of small laboratory animals caused by encephalomyocarditis virus (strain EMK-70)]. The results of pathomorphological investigation of the disease in small laboratory animals experimentally induced by the EMC-70 strain of encephalomyocarditis virus isolated from monkeys are presented. Irrespective of the mode of virus injection, the newborn and juvenile mice developed some lesions in the brown fat, transverse-striated muscles, as well as in the brain and heart. In guinea pigs the changes were characterized by the development of severe myocarditis and encephalitis accompanied by viral antigen accumulation. The disease induced by the EMC-70 strain could not be differentiated from the Coxsackie infection by the pathomorphological data. This fact should be taken into consideration in solving some problems pertinent to pathoanatomical diagnosis of viral diseases."}
{"id": "PMID:199296", "title": "Effect of atropine on vascular adrenergic neuroeffector transmission.", "content": "Atropine, homatropine, scopolamine, procaine, lidocaine and phentolamine inhibited the contractile response of rabbit isolated pulmonary artery elicited by electrical-field stimulation. Methylatropine had no effect. The inhibition induced by atropine (2 x 10(-6)-2 x 10(-4) M) had a rapid onset of action and then remained almost constant. The inhibition was slowly reversible. The potency of atropine as an inhibitor of responses to field stimulation was very much less than the potency of phentolamine. The inhibition was not antagonized by cocaine or (+)-amphetamine. Atropine (3 x 10(-5) and 3 x 10(-4) M) enhanced the electrical-field-stimulation-induced outflow of tritium from the pulmonary artery preloaded with 3H-(-)-noradrenaline. In contrast, atropine in a concentration-dependent manner either had no effect or slightly decreased the tyramine-induced outflow of tritium. Atropine reduced the contractile response of the pulmonary artery evoked by tyramine. Atropine (10(-4) and 3 x 10(-4) M) and phentolamine inhibited the arterial contractions elicited by exogenous (-)-noradrenaline in an apparently competitive manner. The contractions of rabbit isolated aorta elicited by (-)-noradrenaline, serotonin and histamine were inhibited by atropine (10(-5) and 10(-4) M). Atropine was very much less potent in antagonizing noradrenaline, histamine and serotonin than in antagonizing acetylcholine. tthe inhibotory potency of atropine, procaine and lidocaine on the accumulation of 3H-(-)-noradrenaline by rabbit aorta in vitro was much less than that of cocaine. The relationship between the aortic concentration of 3H-atropine and in vitro accumulation was almost linear. The accumulation was slightly higher at 37 degrees C than at 1 degree C. The results suggest that atropine blocks alpha-adrenoceptors, both presynaptically at the adrenergic neurone terminals and postsynaptically at the smooth muscle. In addition, atropine may possibly act in a nonspecific manner at postsynaptic sites.", "contents": "Effect of atropine on vascular adrenergic neuroeffector transmission. Atropine, homatropine, scopolamine, procaine, lidocaine and phentolamine inhibited the contractile response of rabbit isolated pulmonary artery elicited by electrical-field stimulation. Methylatropine had no effect. The inhibition induced by atropine (2 x 10(-6)-2 x 10(-4) M) had a rapid onset of action and then remained almost constant. The inhibition was slowly reversible. The potency of atropine as an inhibitor of responses to field stimulation was very much less than the potency of phentolamine. The inhibition was not antagonized by cocaine or (+)-amphetamine. Atropine (3 x 10(-5) and 3 x 10(-4) M) enhanced the electrical-field-stimulation-induced outflow of tritium from the pulmonary artery preloaded with 3H-(-)-noradrenaline. In contrast, atropine in a concentration-dependent manner either had no effect or slightly decreased the tyramine-induced outflow of tritium. Atropine reduced the contractile response of the pulmonary artery evoked by tyramine. Atropine (10(-4) and 3 x 10(-4) M) and phentolamine inhibited the arterial contractions elicited by exogenous (-)-noradrenaline in an apparently competitive manner. The contractions of rabbit isolated aorta elicited by (-)-noradrenaline, serotonin and histamine were inhibited by atropine (10(-5) and 10(-4) M). Atropine was very much less potent in antagonizing noradrenaline, histamine and serotonin than in antagonizing acetylcholine. tthe inhibotory potency of atropine, procaine and lidocaine on the accumulation of 3H-(-)-noradrenaline by rabbit aorta in vitro was much less than that of cocaine. The relationship between the aortic concentration of 3H-atropine and in vitro accumulation was almost linear. The accumulation was slightly higher at 37 degrees C than at 1 degree C. The results suggest that atropine blocks alpha-adrenoceptors, both presynaptically at the adrenergic neurone terminals and postsynaptically at the smooth muscle. In addition, atropine may possibly act in a nonspecific manner at postsynaptic sites."}
{"id": "PMID:199310", "title": "Pharmacological and certain chemical properties of AH 10407, an unusually short-acting, competitive neuromuscular blocking drug, and some related compounds.", "content": "1,1-Azobis[3-methyl-2-phenylbenzimidazolinium]dimethanesulphonate (AH 10407) has an ultrashort, competitive neuromuscular blocking action in the mouse, cat, dog, Cynamolgus monkey and cotton-eared marmoset. 2 AH 10407 is chemically unstable in bicarbonate-containing solutions and is degraded to inactive products. The half-life of AH 10407 in vitro in dog and human whole blood and in Krebs physiological solution is about 1.0 minute. In distilled water and in HCO-3-deficient Krebs solution AH 10407 is much more stable. Base catalyzed degradation is shown to be the prime determinant of the duration of action of the drug. 3 Some pharmacological properties of AH 11244 and AH 11056, close analogues of AH 10407, are briefly described and the duration of their neuromuscular blocking actions rationalized by reference to their chemical stabilities.", "contents": "Pharmacological and certain chemical properties of AH 10407, an unusually short-acting, competitive neuromuscular blocking drug, and some related compounds. 1,1-Azobis[3-methyl-2-phenylbenzimidazolinium]dimethanesulphonate (AH 10407) has an ultrashort, competitive neuromuscular blocking action in the mouse, cat, dog, Cynamolgus monkey and cotton-eared marmoset. 2 AH 10407 is chemically unstable in bicarbonate-containing solutions and is degraded to inactive products. The half-life of AH 10407 in vitro in dog and human whole blood and in Krebs physiological solution is about 1.0 minute. In distilled water and in HCO-3-deficient Krebs solution AH 10407 is much more stable. Base catalyzed degradation is shown to be the prime determinant of the duration of action of the drug. 3 Some pharmacological properties of AH 11244 and AH 11056, close analogues of AH 10407, are briefly described and the duration of their neuromuscular blocking actions rationalized by reference to their chemical stabilities."}
{"id": "PMID:199311", "title": "Suppression of transmission of nociceptive impulses by morphine: selective effects of morphine administered in the region of the substantia gelatinosa.", "content": "1 In spinal cats anaesthetized with alpha-chloralose, a study was made of the effects of morphine and naloxone, administered electrophoretically from micropipettes, on the responses of dorsal horn neurones to noxious (raising of skin temperature above 45 degrees C) and innocuous (deflection of hairs) peripheral stimuli.2 Administered near cell bodies, morphine reduced the nociceptive responses of only 2 of 37 cells. Excitation occurred more commonly than depression and abnormalities in action potentials were commonly observed following ejection of morphine. None of these effects of morphine was antagonized by electrophoretically applied naloxone.3 Administered in the substantia gelatinosa from one micropipette while recording responses of deeper neurones with a second micropipette, morphine reduced the nociceptive responses of 15 of 19 neurones. Firing in response to deflection of hairs was not reduced by morphine. Depression of nociceptive responses by morphine was long lasting (>20 minutes). Naloxone ejected into the substantia gelatinosa or given intravenously in doses as low as 0.1 mg/kg antagonized the effects of morphine. The effectiveness of this dose of intravenous naloxone suggests that the concentrations of morphine in the substantia gelatinosa which reduced nociceptive responses were not unlike those present after analgesic doses of systemic morphine. Naloxone alone, and excitant and depressant amino acids ejected into the substantia gelatinosa had little effect on cell firing.4 Both the selective action of morphine on nociceptive responses and the reversal of this action by intravenous naloxone suggest that the opiate receptor present in the substantia gelatinosa is relevant to analgesia produced by opiates given systemically.", "contents": "Suppression of transmission of nociceptive impulses by morphine: selective effects of morphine administered in the region of the substantia gelatinosa. 1 In spinal cats anaesthetized with alpha-chloralose, a study was made of the effects of morphine and naloxone, administered electrophoretically from micropipettes, on the responses of dorsal horn neurones to noxious (raising of skin temperature above 45 degrees C) and innocuous (deflection of hairs) peripheral stimuli.2 Administered near cell bodies, morphine reduced the nociceptive responses of only 2 of 37 cells. Excitation occurred more commonly than depression and abnormalities in action potentials were commonly observed following ejection of morphine. None of these effects of morphine was antagonized by electrophoretically applied naloxone.3 Administered in the substantia gelatinosa from one micropipette while recording responses of deeper neurones with a second micropipette, morphine reduced the nociceptive responses of 15 of 19 neurones. Firing in response to deflection of hairs was not reduced by morphine. Depression of nociceptive responses by morphine was long lasting (>20 minutes). Naloxone ejected into the substantia gelatinosa or given intravenously in doses as low as 0.1 mg/kg antagonized the effects of morphine. The effectiveness of this dose of intravenous naloxone suggests that the concentrations of morphine in the substantia gelatinosa which reduced nociceptive responses were not unlike those present after analgesic doses of systemic morphine. Naloxone alone, and excitant and depressant amino acids ejected into the substantia gelatinosa had little effect on cell firing.4 Both the selective action of morphine on nociceptive responses and the reversal of this action by intravenous naloxone suggest that the opiate receptor present in the substantia gelatinosa is relevant to analgesia produced by opiates given systemically."}
{"id": "PMID:199312", "title": "Studies of hydrolytic enzymes and isoenzymes of normal and neoplastic childhood renal tissues and their tissue cultured cells.", "content": "The hydrolases of acid and alkaline phosphatase and non-specific esterases were investigated by histochemical and electrophoretic techniques in normal and neoplastic renal tissues and their cultured cells. A distinct tumour specific pattern of non-specific esterases was demonstrated in Wilms' tumour. The reasons for the quantitative differences found in the distribution of alkaline phosphatase in Wilms' tumour and their cultured cells are discussed.", "contents": "Studies of hydrolytic enzymes and isoenzymes of normal and neoplastic childhood renal tissues and their tissue cultured cells. The hydrolases of acid and alkaline phosphatase and non-specific esterases were investigated by histochemical and electrophoretic techniques in normal and neoplastic renal tissues and their cultured cells. A distinct tumour specific pattern of non-specific esterases was demonstrated in Wilms' tumour. The reasons for the quantitative differences found in the distribution of alkaline phosphatase in Wilms' tumour and their cultured cells are discussed."}
{"id": "PMID:199313", "title": "Glomerulosclerosis following irradiation and cytotoxic therapy for nephroblastoma.", "content": "A 6-year-old child had a nephrectomy for nephroblastoma followed by radiotherapy and chemotherapy with actinomycin D and vincristine. He died of metastatic disease 13 months after the operation. Autopsy showed a diffuse glomerulosclerosis in the remaining kidney which is attributed to the postoperative therapy.", "contents": "Glomerulosclerosis following irradiation and cytotoxic therapy for nephroblastoma. A 6-year-old child had a nephrectomy for nephroblastoma followed by radiotherapy and chemotherapy with actinomycin D and vincristine. He died of metastatic disease 13 months after the operation. Autopsy showed a diffuse glomerulosclerosis in the remaining kidney which is attributed to the postoperative therapy."}
{"id": "PMID:199316", "title": "Axonal regeneration in the rat sciatic nerve: effect of a conditioning lesion and of dbcAMP.", "content": "After the sciatic nerve had been crushed at the level of the mid-thigh, the rate of outgrowth of the regenerating axons was measured by using the pinch test to locate the leading sensory axons. This standard crush lesion (\"testing\" lesion) elicited axonal outgrowth at a rate of 4.3 +/- 0.1 mm/day, with an initial delay (before the axons entered the degenerating distal stump) of 1.6 days. A \"conditioning\" lesion (transection of the tibial nerve at the ankle), made two weeks before the testing lesion, caused an increase of 23% in the outgrowth rat (P less than 0.02), with no appreciable change in the initial delay. Dibutyryl cyclic AMP (dbcAMP) was found to have no effect on the rate of axonal outgrowth measured by the pinch test. Histological examination of the pinch-tested nerves showed that the drug also had no effect on the numbers of regenerating silver-stained axons or fluorescent noradrenergic axons seen at various levels distal to the testing lesion.", "contents": "Axonal regeneration in the rat sciatic nerve: effect of a conditioning lesion and of dbcAMP. After the sciatic nerve had been crushed at the level of the mid-thigh, the rate of outgrowth of the regenerating axons was measured by using the pinch test to locate the leading sensory axons. This standard crush lesion (\"testing\" lesion) elicited axonal outgrowth at a rate of 4.3 +/- 0.1 mm/day, with an initial delay (before the axons entered the degenerating distal stump) of 1.6 days. A \"conditioning\" lesion (transection of the tibial nerve at the ankle), made two weeks before the testing lesion, caused an increase of 23% in the outgrowth rat (P less than 0.02), with no appreciable change in the initial delay. Dibutyryl cyclic AMP (dbcAMP) was found to have no effect on the rate of axonal outgrowth measured by the pinch test. Histological examination of the pinch-tested nerves showed that the drug also had no effect on the numbers of regenerating silver-stained axons or fluorescent noradrenergic axons seen at various levels distal to the testing lesion."}
{"id": "PMID:199317", "title": "The mechanism of actions of collagenase on the inhibition of release of acetylcholine from synaptosomal preparations.", "content": "The release of acetylcholine from synaptosomal preparations from bovine superior cervical ganglia and rat cortex was inhibited when the preparations were pretreated with collagenase. The inhibition of release could be overcome with the calcium ionophore A23187. Collagenase treatment was shown to inhibit the uptake of calcium into the preparations. In addition, gel electrophoresis of synaptosomal membranes revealed two missing high molecular weight proteins when either synaptosomes or synaptosomal membranes were incubated with collagenase.", "contents": "The mechanism of actions of collagenase on the inhibition of release of acetylcholine from synaptosomal preparations. The release of acetylcholine from synaptosomal preparations from bovine superior cervical ganglia and rat cortex was inhibited when the preparations were pretreated with collagenase. The inhibition of release could be overcome with the calcium ionophore A23187. Collagenase treatment was shown to inhibit the uptake of calcium into the preparations. In addition, gel electrophoresis of synaptosomal membranes revealed two missing high molecular weight proteins when either synaptosomes or synaptosomal membranes were incubated with collagenase."}
{"id": "PMID:199318", "title": "Paradoxical sleep and brain catecholamines in the rat after single and repeated administration of alpha-methyl-paratyrosine.", "content": "This study is concerned with the role of catecholamines (CA) in the regulation of paradoxical sleep (PS) in the rat. Alpha-methyl-paratyrosine (alphaMPT), an inhibitor of tyrosine hydroxylase, was used in a multiple administration schedule in order to avoid toxic effects. From 2 to 10 doses of 75 mg/kg of alphaMPT, a progressive reduction of green fluorescence occurred in CA cell bodies as well as in terminals. The green fluorescence reduction was faster in dopaminergic than in noradrenergic neurons, and faster in cell bodies than in terminals. Sleep recordings showed a slight increase of PS after one or two doses of 75 mg/kg of alphaMPT, and a dose-related decrease after 3-7 injections. After two doses of 75 mg/kg, the number of PS phases was significantly increased. This can be due to the release of a non-CA PS primer mechanism. These experiments support the view that an intact synaptic transmission in CA neurons is necessary for the realization of PS.", "contents": "Paradoxical sleep and brain catecholamines in the rat after single and repeated administration of alpha-methyl-paratyrosine. This study is concerned with the role of catecholamines (CA) in the regulation of paradoxical sleep (PS) in the rat. Alpha-methyl-paratyrosine (alphaMPT), an inhibitor of tyrosine hydroxylase, was used in a multiple administration schedule in order to avoid toxic effects. From 2 to 10 doses of 75 mg/kg of alphaMPT, a progressive reduction of green fluorescence occurred in CA cell bodies as well as in terminals. The green fluorescence reduction was faster in dopaminergic than in noradrenergic neurons, and faster in cell bodies than in terminals. Sleep recordings showed a slight increase of PS after one or two doses of 75 mg/kg of alphaMPT, and a dose-related decrease after 3-7 injections. After two doses of 75 mg/kg, the number of PS phases was significantly increased. This can be due to the release of a non-CA PS primer mechanism. These experiments support the view that an intact synaptic transmission in CA neurons is necessary for the realization of PS."}
{"id": "PMID:199319", "title": "Post-synaptic potentials recorded from afferent nerve fibres of the posterior semicircular canal in the frog.", "content": "Glass microelectrode recordings were made from single fibres of the posterior ampullary nerve in the isolated labyrinth of the frog (Rana esculenta). Potentials were recorded both at rest and during rotatory stimulation of the canal. At rest, the tracings revealed an intense background of small, largely summated potentials (0.5-10 mV amplitude, 3-6 msec duration), which underlay the discharge of spikes in all the impaled units. The frequency of the subthreshold events was related to the frequency of the propagated spikes, the latter ranging from 0 to 40/sec. Stimulation modulated the frequency of both spikes and subthreshold potentials, whose summation during excitation led to a positive shift of the fibre membrane potential. The small potentials proved to be dependent on Ca2+ and Mg2+ levels in the bath. Antidromic-stimulation of the posterior ampullary nerve indicated that the observed events do not represent an artifact due to extracellular field interference related to spike activity in the neighbouring fibres. Tetrodotoxin (10(-7)-10(-6) g/ml) applied externally to the preparation or previously perfused through the frog vessels abolishes the propagated spikes but left unaffected the small potentials which, even under drug treatment, were normally modulated by the stimulus. The subthreshold potentials thus appear to be EPSPs generated at the cyto-neural junction between the hair cells and the endings of the ampullary nerve fibres.", "contents": "Post-synaptic potentials recorded from afferent nerve fibres of the posterior semicircular canal in the frog. Glass microelectrode recordings were made from single fibres of the posterior ampullary nerve in the isolated labyrinth of the frog (Rana esculenta). Potentials were recorded both at rest and during rotatory stimulation of the canal. At rest, the tracings revealed an intense background of small, largely summated potentials (0.5-10 mV amplitude, 3-6 msec duration), which underlay the discharge of spikes in all the impaled units. The frequency of the subthreshold events was related to the frequency of the propagated spikes, the latter ranging from 0 to 40/sec. Stimulation modulated the frequency of both spikes and subthreshold potentials, whose summation during excitation led to a positive shift of the fibre membrane potential. The small potentials proved to be dependent on Ca2+ and Mg2+ levels in the bath. Antidromic-stimulation of the posterior ampullary nerve indicated that the observed events do not represent an artifact due to extracellular field interference related to spike activity in the neighbouring fibres. Tetrodotoxin (10(-7)-10(-6) g/ml) applied externally to the preparation or previously perfused through the frog vessels abolishes the propagated spikes but left unaffected the small potentials which, even under drug treatment, were normally modulated by the stimulus. The subthreshold potentials thus appear to be EPSPs generated at the cyto-neural junction between the hair cells and the endings of the ampullary nerve fibres."}
{"id": "PMID:199321", "title": "Responses of the immature fowl to a single injection of adrenocorticotrophic hormone.", "content": "Chicks, aged 1 or 21 d, were injected with long-acting ACTH (6, 12, 30 or 60 IU/kg) and changes in plasma glucose and cholesterol and in adrenal weight and cholesterol measured. 2. No consistent response was observed in the 1-d-old chicks. 3. Hyperglycaemia and adrenal cholesterol depletion could be demonstrated in the 3-week-old bird at all doses. 4. The duration of the hyperglycaemic response was dose-dependent but there was only limited evidence that adrenal cholesterol depletion was similarly dependent. 5. Starving the 3-week-old bird overnight led to a significant hypercholesteraemia which was reduced after ACTH. In contrast no change in plasma cholesterol concentration was noted in fully fed birds.", "contents": "Responses of the immature fowl to a single injection of adrenocorticotrophic hormone. Chicks, aged 1 or 21 d, were injected with long-acting ACTH (6, 12, 30 or 60 IU/kg) and changes in plasma glucose and cholesterol and in adrenal weight and cholesterol measured. 2. No consistent response was observed in the 1-d-old chicks. 3. Hyperglycaemia and adrenal cholesterol depletion could be demonstrated in the 3-week-old bird at all doses. 4. The duration of the hyperglycaemic response was dose-dependent but there was only limited evidence that adrenal cholesterol depletion was similarly dependent. 5. Starving the 3-week-old bird overnight led to a significant hypercholesteraemia which was reduced after ACTH. In contrast no change in plasma cholesterol concentration was noted in fully fed birds."}
{"id": "PMID:199323", "title": "[Effect of cyclic AMP on retrogression of the Mullerian ducts in chick embryos].", "content": "Theophyllin and puromycine, inhibitors of the enzyme phosphodiesterase and AMPc are all able to inhibit the retrogression of mullerian ducts in the female chick embryo, grafted with an embryonic testis. We can think that these results are explained by an inhibitory action of AMPc on the mechanisms responsible for the mullerian retrogression. So the chick embryo reacts similarly as do the mammalian embryo.", "contents": "[Effect of cyclic AMP on retrogression of the Mullerian ducts in chick embryos]. Theophyllin and puromycine, inhibitors of the enzyme phosphodiesterase and AMPc are all able to inhibit the retrogression of mullerian ducts in the female chick embryo, grafted with an embryonic testis. We can think that these results are explained by an inhibitory action of AMPc on the mechanisms responsible for the mullerian retrogression. So the chick embryo reacts similarly as do the mammalian embryo."}
{"id": "PMID:199320", "title": "Regional distribution of beta-lipotropin converting enzymes in rat pituitary and brain.", "content": "Among the brain areas studied only pars distalis and pars intermedia are found to contain beta-lipotropin activating enzyme indicating the these may be the exclusive organs for a physiologically significant conversion of beta-lipotropin into beta-endorphin. beta-Endorphin inactivating enzyme is found to be rather uniformly distributed in all the pituitary and brain regions. alpha-and gamma-endorphins are presumably formed by the action of the enzyme on beta-endorphin.", "contents": "Regional distribution of beta-lipotropin converting enzymes in rat pituitary and brain. Among the brain areas studied only pars distalis and pars intermedia are found to contain beta-lipotropin activating enzyme indicating the these may be the exclusive organs for a physiologically significant conversion of beta-lipotropin into beta-endorphin. beta-Endorphin inactivating enzyme is found to be rather uniformly distributed in all the pituitary and brain regions. alpha-and gamma-endorphins are presumably formed by the action of the enzyme on beta-endorphin."}
{"id": "PMID:199339", "title": "Virions associated with acute gastroenteritis in Vancouver, 1976.", "content": "Virions were identified by electron microscopic observation of unconcentrated extracts of feces obtained from 55 (33%) of 167 children aged 3 weeks to 5 years who were hospitalized with acute gastroenteritis at Children's Hospital, Vancouver between January and December 1976. Morphologic types included 30 rotavirus, 15 adenovirus, 5 astrovirus and 5 picornavirus-like particles.", "contents": "Virions associated with acute gastroenteritis in Vancouver, 1976. Virions were identified by electron microscopic observation of unconcentrated extracts of feces obtained from 55 (33%) of 167 children aged 3 weeks to 5 years who were hospitalized with acute gastroenteritis at Children's Hospital, Vancouver between January and December 1976. Morphologic types included 30 rotavirus, 15 adenovirus, 5 astrovirus and 5 picornavirus-like particles."}
{"id": "PMID:199341", "title": "Primary mucinous carcinoma of skin: histochemistry and electron microscopy.", "content": "Two primary mucinous carcinomas of skin were studied by histochemistry and by light and electron microscopy. Enzyme histochemistry showed a pattern of reactivity similar to that found in eccrine secretory epithelium. Mucin histochemistry substantiated previous reports of probable sialomucin formation. Electron microscopy revealed a highly differentiated neoplasm with a mode of mucin secretion similar to that observed in the dark (mucinous) cell of the eccrine coil. The natural history of mucinous carcinoma of skin indicates that although local growth is the rule, lymph node metastasis may occur.", "contents": "Primary mucinous carcinoma of skin: histochemistry and electron microscopy. Two primary mucinous carcinomas of skin were studied by histochemistry and by light and electron microscopy. Enzyme histochemistry showed a pattern of reactivity similar to that found in eccrine secretory epithelium. Mucin histochemistry substantiated previous reports of probable sialomucin formation. Electron microscopy revealed a highly differentiated neoplasm with a mode of mucin secretion similar to that observed in the dark (mucinous) cell of the eccrine coil. The natural history of mucinous carcinoma of skin indicates that although local growth is the rule, lymph node metastasis may occur."}
{"id": "PMID:199342", "title": "Erythrophagocytosis by epithelial cells of a breast carcinoma.", "content": "Erytrophagocytosis by epithelial tumor cells has been observed in metastases of ductal carcinoma of the female breast. Some malignant cells of this tumor seem to be capable of phagocytizing and digesting extravasated red blood cells with for formation of residual hemosiderin probably from their hemoglobin content. Erythrophagocytosis has been observed only in hemorrhagic areas of the tumor. Erythrophagocytosis has been observed only in hemorrhagic areas of the tumor. Although the nature of this phenomenon is unknown, it is postulated that acquired hematological disturbancess during the natural course of the malignant disease affect the surface of the red blood cells making them vulnerable to phagocytosis by the malignant cells. This case seems to represent the second time such a phenomenon has been reported in an epithelial neoplasm in man. However, it has been more frequently observed in reticulo-endothelial malignancies. The possible occurence of this phenomenon should alert pathologists to search for it in primary and metastatic epithelial tumors and in living patients to correlate pertinent hematological studies in an attempt to elucidate its possible significance.", "contents": "Erythrophagocytosis by epithelial cells of a breast carcinoma. Erytrophagocytosis by epithelial tumor cells has been observed in metastases of ductal carcinoma of the female breast. Some malignant cells of this tumor seem to be capable of phagocytizing and digesting extravasated red blood cells with for formation of residual hemosiderin probably from their hemoglobin content. Erythrophagocytosis has been observed only in hemorrhagic areas of the tumor. Erythrophagocytosis has been observed only in hemorrhagic areas of the tumor. Although the nature of this phenomenon is unknown, it is postulated that acquired hematological disturbancess during the natural course of the malignant disease affect the surface of the red blood cells making them vulnerable to phagocytosis by the malignant cells. This case seems to represent the second time such a phenomenon has been reported in an epithelial neoplasm in man. However, it has been more frequently observed in reticulo-endothelial malignancies. The possible occurence of this phenomenon should alert pathologists to search for it in primary and metastatic epithelial tumors and in living patients to correlate pertinent hematological studies in an attempt to elucidate its possible significance."}
{"id": "PMID:199343", "title": "Observation of nervous tissue in a Wilms' tumor: its histogenetic significance.", "content": "A case of Wilms' tumor occurring in a horseshoe kidney is reported in which bona fide nervous tissue containing ganglion cells was observed. This finding cannot be reconciled with the currently held \"metanephrogenic blastema\" theory of the histogenesis of this tumor. Masson's concept of \"neuroepithelial origin\" of the Wilms' tumor should be re-evaluated.", "contents": "Observation of nervous tissue in a Wilms' tumor: its histogenetic significance. A case of Wilms' tumor occurring in a horseshoe kidney is reported in which bona fide nervous tissue containing ganglion cells was observed. This finding cannot be reconciled with the currently held \"metanephrogenic blastema\" theory of the histogenesis of this tumor. Masson's concept of \"neuroepithelial origin\" of the Wilms' tumor should be re-evaluated."}
{"id": "PMID:199344", "title": "The histogenesis and development of pulmonary tumorlets.", "content": "A lung, which was surgically removed from a patient who had oat cell carcinoma, contained multiple tumorlets and showed extensive Kultschitsky-type cell proliferation of bronchial and bronchiolar mucosa. On the basis of light and electron microscopic observations, it is shown that pulmonary tumorlets arise from focal areas of bronchial and bronchiolar Kultschitsky cell proliferation which may advance to luminal obliteration. Involvement of the pulmonary parenchyma takes place by extension of these newly proliferated cells along the terminal branches of the bronchiolar tree or by penetration of the bronchial or bronchiolar wall; the latter process evokes a striking proliferation of connective tissue which forms the matrix in which the cells of some fully developed tumorlets are embedded. Because of striking morphologic similarities between tumorlets and spindle cell carcinoid tumors, and the proven origin of tumorlets from pulmonary Kultschitsky-type cells, it is suggested that the more complete and histogenetically acceptable term \"carcinoid tumor-let\" be used to distinguish this lesion from other forms of epithelial proliferations in the lung.", "contents": "The histogenesis and development of pulmonary tumorlets. A lung, which was surgically removed from a patient who had oat cell carcinoma, contained multiple tumorlets and showed extensive Kultschitsky-type cell proliferation of bronchial and bronchiolar mucosa. On the basis of light and electron microscopic observations, it is shown that pulmonary tumorlets arise from focal areas of bronchial and bronchiolar Kultschitsky cell proliferation which may advance to luminal obliteration. Involvement of the pulmonary parenchyma takes place by extension of these newly proliferated cells along the terminal branches of the bronchiolar tree or by penetration of the bronchial or bronchiolar wall; the latter process evokes a striking proliferation of connective tissue which forms the matrix in which the cells of some fully developed tumorlets are embedded. Because of striking morphologic similarities between tumorlets and spindle cell carcinoid tumors, and the proven origin of tumorlets from pulmonary Kultschitsky-type cells, it is suggested that the more complete and histogenetically acceptable term \"carcinoid tumor-let\" be used to distinguish this lesion from other forms of epithelial proliferations in the lung."}
{"id": "PMID:199345", "title": "Tendosynovial sarcoma: a clinicopathological study of 136 cases.", "content": "A series of 136 cases of tendosynovial sarcomas were studied from the histologic point of view. All of the primary, recurrent and metastatic tumors were reclassified according to histologic type, anatomic site and size; age and sex of patients and modality of surgical treatment. The overall 5-year survival rate was 40%. Among the factors which most favorably influenced the prognosis were: small size (74%, 5-year survival), \"exposed\" primary site (53%, 5-year survival), and histologic type (biphasic form: 55%, 5-year survival and epithelioid sarcoma: 58%, 5-year survival). Children and elderly patients had also better than the average prognosis. Sixty percent of the sarcomas recurred after wide local excision. Twelve percent of the tumors metastasized to regional lymph nodes and 10% to bones. Almost all of the 24 patients who were autopsied died because of cardio-pulmonary insufficiency due to massive pleuropulmonary metastasis. It is hoped that better understanding of the natural history of these tumors will lead to optimal local and systemic therapy and better survival.", "contents": "Tendosynovial sarcoma: a clinicopathological study of 136 cases. A series of 136 cases of tendosynovial sarcomas were studied from the histologic point of view. All of the primary, recurrent and metastatic tumors were reclassified according to histologic type, anatomic site and size; age and sex of patients and modality of surgical treatment. The overall 5-year survival rate was 40%. Among the factors which most favorably influenced the prognosis were: small size (74%, 5-year survival), \"exposed\" primary site (53%, 5-year survival), and histologic type (biphasic form: 55%, 5-year survival and epithelioid sarcoma: 58%, 5-year survival). Children and elderly patients had also better than the average prognosis. Sixty percent of the sarcomas recurred after wide local excision. Twelve percent of the tumors metastasized to regional lymph nodes and 10% to bones. Almost all of the 24 patients who were autopsied died because of cardio-pulmonary insufficiency due to massive pleuropulmonary metastasis. It is hoped that better understanding of the natural history of these tumors will lead to optimal local and systemic therapy and better survival."}
{"id": "PMID:199346", "title": "Perianal mucinous adenocarcinoma.", "content": "Perianal mucinous adenocarcinoma, also known as anal duct or anal gland carcinoma, is a rare tumor usually associated with chronic fistulae-in-ano. Whether the tumor occurs primarily and the fistula is a secondary manifestation, or whether this tumor arises in a chronic fistulous tract is debatable. Diagnosis can be made only by open deep biopsy of the buttock mass, and, due to the low grade histologic appearance of the malignancy, an incorrect diagnosis is frequently made. Treatment is abdominoperineal resection with wide removal of the buttock mass.", "contents": "Perianal mucinous adenocarcinoma. Perianal mucinous adenocarcinoma, also known as anal duct or anal gland carcinoma, is a rare tumor usually associated with chronic fistulae-in-ano. Whether the tumor occurs primarily and the fistula is a secondary manifestation, or whether this tumor arises in a chronic fistulous tract is debatable. Diagnosis can be made only by open deep biopsy of the buttock mass, and, due to the low grade histologic appearance of the malignancy, an incorrect diagnosis is frequently made. Treatment is abdominoperineal resection with wide removal of the buttock mass."}
{"id": "PMID:199347", "title": "A minute hepatocellular carcinoma found in a liver with clonorchis sinensis infection: report of two cases.", "content": "Two cases of minute hepatocellular carcinoma (HCC) found in a liver infested with Clonorchis sinensis are described. One had mild infestation with hepatic changes suggestive of posthepatitic cirrhosis, and the other heavy infestation exhibiting secondary biliary cirrhosis with dilated intrahepatic bile ducts and periductal fibrosis. None had evidence of hepatitis B infection. The tumor nodule was solitary, measuring 5 X 7 mm and 10 X 11 mm, respectively, and the cells were differentiated to be classified as Grade I of Edmondson-Steiner's scale of anaplasia. It is not clear whether or not clonorchiasis was etiologically related to HCC, but it was of interest that in both cases the tumor nodule was very small representing the primary lesion without metastasis.", "contents": "A minute hepatocellular carcinoma found in a liver with clonorchis sinensis infection: report of two cases. Two cases of minute hepatocellular carcinoma (HCC) found in a liver infested with Clonorchis sinensis are described. One had mild infestation with hepatic changes suggestive of posthepatitic cirrhosis, and the other heavy infestation exhibiting secondary biliary cirrhosis with dilated intrahepatic bile ducts and periductal fibrosis. None had evidence of hepatitis B infection. The tumor nodule was solitary, measuring 5 X 7 mm and 10 X 11 mm, respectively, and the cells were differentiated to be classified as Grade I of Edmondson-Steiner's scale of anaplasia. It is not clear whether or not clonorchiasis was etiologically related to HCC, but it was of interest that in both cases the tumor nodule was very small representing the primary lesion without metastasis."}
{"id": "PMID:199348", "title": "Metastatic infantile Wilms' tumor and hydrocephalus; a case report with review of the literature.", "content": "A case of infantile metastasizing Wilms' tumor is described clinically and pathologically. The presenting feature was congenital hydrocephalus due to cerebral metastases. The literature is reviewed and four similar examples are found. The unusual pattern of clinical presentation and metastases is emphasized as it may be characteristic for this rare entity.", "contents": "Metastatic infantile Wilms' tumor and hydrocephalus; a case report with review of the literature. A case of infantile metastasizing Wilms' tumor is described clinically and pathologically. The presenting feature was congenital hydrocephalus due to cerebral metastases. The literature is reviewed and four similar examples are found. The unusual pattern of clinical presentation and metastases is emphasized as it may be characteristic for this rare entity."}
{"id": "PMID:199349", "title": "Cystic nephroma.", "content": "The clinical and pathologic findings of four cases of cystic nephroma (so-called \"renal multilocular cyst\") in four infants nephrectomized with the diagnosis of Wilms' tumor are presented. Each lesion consisted of an encapsulated mass composed of cysts separated by thin septa. Histologically the cysts were lined by epithelium, and the septa contained foci of immature metanephric blastema (abundant in one case and sparse in another). rhabdomyocytes and mature tubules. Neither embryonic ducts nor cartilage were seen. One cystic lesion was adjacent to a nephroblastoma which formed a separate nodule. No recurrences of metastases developed, and the only death was due to postoperative sepsis. These lesions are considered by some authors to be dysplasia, while others interpret them as benign neoplasms. Our findings and a review of the literature probably represent the differentiated counterpart of nephroblastoma.", "contents": "Cystic nephroma. The clinical and pathologic findings of four cases of cystic nephroma (so-called \"renal multilocular cyst\") in four infants nephrectomized with the diagnosis of Wilms' tumor are presented. Each lesion consisted of an encapsulated mass composed of cysts separated by thin septa. Histologically the cysts were lined by epithelium, and the septa contained foci of immature metanephric blastema (abundant in one case and sparse in another). rhabdomyocytes and mature tubules. Neither embryonic ducts nor cartilage were seen. One cystic lesion was adjacent to a nephroblastoma which formed a separate nodule. No recurrences of metastases developed, and the only death was due to postoperative sepsis. These lesions are considered by some authors to be dysplasia, while others interpret them as benign neoplasms. Our findings and a review of the literature probably represent the differentiated counterpart of nephroblastoma."}
{"id": "PMID:199350", "title": "Intracerebral delayed hypersensitivity reactions in glioblastoma multiforme patients.", "content": "Patients with malignant gliomas who had undergone BCG inoculation were injected intratumorally with PPD to induce an intratumoral delayed hypersensitivity reaction. Histopathological examination of the tumor before and after PPD injections revealed that chronic inflammatory responses were increased after injection in four of the five patients. In no case, however, was the response more than moderate, and in no case did the inflammatory response encompass the tumor at its peripheral margins. Intracerebral delayed hypersensitivity reactions were evoked in humans with acceptable morbidity. The mild reactions evoked did not cause detectable tumor regression.", "contents": "Intracerebral delayed hypersensitivity reactions in glioblastoma multiforme patients. Patients with malignant gliomas who had undergone BCG inoculation were injected intratumorally with PPD to induce an intratumoral delayed hypersensitivity reaction. Histopathological examination of the tumor before and after PPD injections revealed that chronic inflammatory responses were increased after injection in four of the five patients. In no case, however, was the response more than moderate, and in no case did the inflammatory response encompass the tumor at its peripheral margins. Intracerebral delayed hypersensitivity reactions were evoked in humans with acceptable morbidity. The mild reactions evoked did not cause detectable tumor regression."}
{"id": "PMID:199353", "title": "A possible involvement of cya gene in the synthesis of cyclic guanosine 3':5'-monophosphate in E. coli.", "content": "Based on the following genetical experiments, the cya gene in E. coli was shown to be involved in the synthesis of both cyclic AMP and cyclic GMP. First, all five independent cya-deficient mutants accumulated exceedingly low amounts of cyclic GMP. Second, the ability to form both cyclic AMP and cyclic GMP was simultaneously restored by transduction of an intact cya locus to one of the above cya-deficient mutants. Third, a spontaneous revertant from one of the above mutants regained the synthetic activity for cyclic GMP as well as for cyclic AMP. Fourth, the characteristic of a strain overproducing cyclic GMP was co-transduced with the cya locus. These results suggest that the synthesis of both cyclic GMP and cyclic AMP is mediated by the same enzyme, adenylate cyclase, Interestingly, a reciprocal effect of glucose starvation was observed on the accumulation of both cyclic nucleotides. The formation of cyclic AMP was greatly enhanced on glucose starvation, whereas that of cyclic GMP proceeded at a slower rate than in the presence of glucose. This effect was observed only in cells carrying normal cya and crp genes, but not in a cya-altered or a crp-deficient strain.", "contents": "A possible involvement of cya gene in the synthesis of cyclic guanosine 3':5'-monophosphate in E. coli. Based on the following genetical experiments, the cya gene in E. coli was shown to be involved in the synthesis of both cyclic AMP and cyclic GMP. First, all five independent cya-deficient mutants accumulated exceedingly low amounts of cyclic GMP. Second, the ability to form both cyclic AMP and cyclic GMP was simultaneously restored by transduction of an intact cya locus to one of the above cya-deficient mutants. Third, a spontaneous revertant from one of the above mutants regained the synthetic activity for cyclic GMP as well as for cyclic AMP. Fourth, the characteristic of a strain overproducing cyclic GMP was co-transduced with the cya locus. These results suggest that the synthesis of both cyclic GMP and cyclic AMP is mediated by the same enzyme, adenylate cyclase, Interestingly, a reciprocal effect of glucose starvation was observed on the accumulation of both cyclic nucleotides. The formation of cyclic AMP was greatly enhanced on glucose starvation, whereas that of cyclic GMP proceeded at a slower rate than in the presence of glucose. This effect was observed only in cells carrying normal cya and crp genes, but not in a cya-altered or a crp-deficient strain."}
{"id": "PMID:199354", "title": "Overlapping of the VP2-VP3 gene and the VP1 gene in the SV40 genome.", "content": "The nucleotide sequence of the SV40 Hind E fragment has been determined mainly by the partial chemical degradation procedure of Maxam and Gilbert (1977). The sequence of the strand with the same polarity as the late messenger RNA shows only one open reading frame for translation. Considering that VP3 corresponds to the carbosyl terminal part of VP2, and considering various evidence which indicates that the SV40 Hind E segment is part of the amino acid sequence of VP2-VP3. It continues clockwise in Hind K, where it terminates with a UAA signal. The latter is located 110 nucleotides beyond the initiation signal for the major structural protein VP1 (Fiers et al., 1975; Van de Voorde et al., 1976). Hence this small overlapping region of the genome codes for the synthesis of three different proteins in two different reading frames. The deduced amino acid sequence covers a major part of the vp3 poly peptide, and the amino acid composition is in good agreement with published values (Greenaway and Levine, 1973).", "contents": "Overlapping of the VP2-VP3 gene and the VP1 gene in the SV40 genome. The nucleotide sequence of the SV40 Hind E fragment has been determined mainly by the partial chemical degradation procedure of Maxam and Gilbert (1977). The sequence of the strand with the same polarity as the late messenger RNA shows only one open reading frame for translation. Considering that VP3 corresponds to the carbosyl terminal part of VP2, and considering various evidence which indicates that the SV40 Hind E segment is part of the amino acid sequence of VP2-VP3. It continues clockwise in Hind K, where it terminates with a UAA signal. The latter is located 110 nucleotides beyond the initiation signal for the major structural protein VP1 (Fiers et al., 1975; Van de Voorde et al., 1976). Hence this small overlapping region of the genome codes for the synthesis of three different proteins in two different reading frames. The deduced amino acid sequence covers a major part of the vp3 poly peptide, and the amino acid composition is in good agreement with published values (Greenaway and Levine, 1973)."}
{"id": "PMID:199355", "title": "Further characterization of Sendai virus DI-RNAs: a model for their generation.", "content": "Sendai virus DI-RNAs which contain complementary ends have been characterized as follows. First, the complementary ends of three DI-RNAs, although somewhat different in size (110-150 base pairs), contain sequences that are both identical to each other and to the 5' end of the nondefective (ND) genome. Second, almost all the sequences contained sequences that are both identical to each other and to the 5' end of the nondefective (ND) genome. Second, almost all the sequences contained in the DI-RNAs derive from sequences that are contiguous to the 5' end of the ND genome. The ND genome, on the other hand, does not contain any sequences that are complementary to its 5' end. A genetic map and a model for the generation of the Sendai DI-RNAs are presented.", "contents": "Further characterization of Sendai virus DI-RNAs: a model for their generation. Sendai virus DI-RNAs which contain complementary ends have been characterized as follows. First, the complementary ends of three DI-RNAs, although somewhat different in size (110-150 base pairs), contain sequences that are both identical to each other and to the 5' end of the nondefective (ND) genome. Second, almost all the sequences contained sequences that are both identical to each other and to the 5' end of the nondefective (ND) genome. Second, almost all the sequences contained in the DI-RNAs derive from sequences that are contiguous to the 5' end of the ND genome. The ND genome, on the other hand, does not contain any sequences that are complementary to its 5' end. A genetic map and a model for the generation of the Sendai DI-RNAs are presented."}
{"id": "PMID:199357", "title": "Adenylyl cyclase and the control of cell differentiation in Dictyostelium dicoideum.", "content": "Adenylyl cyclase is part of a biochemical network that controls cell differentiation in Dictyostelium discoideum. At a certain stage of development the enzyme is rhythmically activated, with periods of about 8 min. These oscillations are superimposed upon an increase of the basal activity extending over a period of hours. The basal activity remains low in a mutant blocked at an early stage of development. In strain Ax-2 two periods of strongly increasing basal activity have been found: the first from 2 to 4 h after the end of the growth phase, the other beginning at about 8 h. Based on the periodic regulation of adenylyl cyclase, cyclic AMP is released into the extracellular space in the form of pulses. Application of cyclic-AMP pulses, but not its continuous influx, stimulates the increase of basal adenylyl cyclase activity. Two other constituents of the cyclic-AMP signal system cyclic-AMP receptors and cell-surface phosphodiesterase, are similarly controlled. The principal importance of positive feedback loops in a network controlling cell differentiation is discussed.", "contents": "Adenylyl cyclase and the control of cell differentiation in Dictyostelium dicoideum. Adenylyl cyclase is part of a biochemical network that controls cell differentiation in Dictyostelium discoideum. At a certain stage of development the enzyme is rhythmically activated, with periods of about 8 min. These oscillations are superimposed upon an increase of the basal activity extending over a period of hours. The basal activity remains low in a mutant blocked at an early stage of development. In strain Ax-2 two periods of strongly increasing basal activity have been found: the first from 2 to 4 h after the end of the growth phase, the other beginning at about 8 h. Based on the periodic regulation of adenylyl cyclase, cyclic AMP is released into the extracellular space in the form of pulses. Application of cyclic-AMP pulses, but not its continuous influx, stimulates the increase of basal adenylyl cyclase activity. Two other constituents of the cyclic-AMP signal system cyclic-AMP receptors and cell-surface phosphodiesterase, are similarly controlled. The principal importance of positive feedback loops in a network controlling cell differentiation is discussed."}
{"id": "PMID:199367", "title": "[Cellular contaminants and structural proteins of Rous sarcoma virus (RSV), studied by polyacrylamide gel electrophoresis].", "content": "The number of polypeptides in highly purified preparations of RSV, of two different subgroups, produced in culture, has been compared to the polypeptides present in the supernatant of uninfected cultures and processed in identical manner. The analysis of PAGE-SDS shows that from 13 to 18 polypeptides present in viral preparations may be cellular contaminants. Fewer contaminating polypeptides are found in the myeloblastosis virus purified from plasma of Chicken.", "contents": "[Cellular contaminants and structural proteins of Rous sarcoma virus (RSV), studied by polyacrylamide gel electrophoresis]. The number of polypeptides in highly purified preparations of RSV, of two different subgroups, produced in culture, has been compared to the polypeptides present in the supernatant of uninfected cultures and processed in identical manner. The analysis of PAGE-SDS shows that from 13 to 18 polypeptides present in viral preparations may be cellular contaminants. Fewer contaminating polypeptides are found in the myeloblastosis virus purified from plasma of Chicken."}
{"id": "PMID:199368", "title": "[Measurement of cyclic AMP in the islets of Langerhans of newborn rats. Effect of amino acids].", "content": "Radioimmunoassay of cyclic AMP (cAMP) in the islets of Langerhans from 48-64 h old Rats was performed after succinylation of the samples. cAMP was detected at 0.03 nM. The cAMP content of islets increases when L-arginine, L-lysine and L alanine are added together in the incubation medium at a concentration of 5-10 mM each. When phosphodiesterase is inhibited by theophylline the three amino acids considerably increase the cAMP content of islets. Thus an increase in cAMP content of the islets was observed with a concentration of amino acids which is efficient in stimulating the insulin and glucagon secretion.", "contents": "[Measurement of cyclic AMP in the islets of Langerhans of newborn rats. Effect of amino acids]. Radioimmunoassay of cyclic AMP (cAMP) in the islets of Langerhans from 48-64 h old Rats was performed after succinylation of the samples. cAMP was detected at 0.03 nM. The cAMP content of islets increases when L-arginine, L-lysine and L alanine are added together in the incubation medium at a concentration of 5-10 mM each. When phosphodiesterase is inhibited by theophylline the three amino acids considerably increase the cAMP content of islets. Thus an increase in cAMP content of the islets was observed with a concentration of amino acids which is efficient in stimulating the insulin and glucagon secretion."}
{"id": "PMID:199369", "title": "[Variation in the toxicity of various silicas in relation to the duration of presence in the body].", "content": "The toxic effect of two forms of sand on the lung was investigated by tracheal injection in Rats. After a latent period with low toxicity, more and more extensive pulmonary lesions, comparable to typical silicotic lesions, appear progressively. On the basis of some observations, the hypothesis is put forward that the impurities present in the dust have a retardative effect.", "contents": "[Variation in the toxicity of various silicas in relation to the duration of presence in the body]. The toxic effect of two forms of sand on the lung was investigated by tracheal injection in Rats. After a latent period with low toxicity, more and more extensive pulmonary lesions, comparable to typical silicotic lesions, appear progressively. On the basis of some observations, the hypothesis is put forward that the impurities present in the dust have a retardative effect."}
{"id": "PMID:199370", "title": "[Receptors for cytomegaloviruses on the surface of human lymphocytes].", "content": "The relationships between cytomegalovirus (CMV) and lymphocytes have already been noted because of: (a) the immunological abnormalities induced by this virus, and (b) activation of latent CMV in the course of lymphocyte reactions associated with anti-histocompatibility antigen immune response. The present work shows that the lymphocyte surface may have specific receptors for CMV. Cultured fibroblasts infected with DMV were incubated with lymphocytes isolated from the blood of human immune subjects. Rosettes defined by the adherence of three or more lymphocytes around a fibroblast were formed in infected preparation while no rosettes were seen with normal control fibroblasts. Approximately 1.2 per cent of lymphocytes were involved in the formation of these rosettes. Rosette formation is inhibited when infected fibroblasts have been incubated with anti-CMV antibodies prior to the addition of lymphocytes.", "contents": "[Receptors for cytomegaloviruses on the surface of human lymphocytes]. The relationships between cytomegalovirus (CMV) and lymphocytes have already been noted because of: (a) the immunological abnormalities induced by this virus, and (b) activation of latent CMV in the course of lymphocyte reactions associated with anti-histocompatibility antigen immune response. The present work shows that the lymphocyte surface may have specific receptors for CMV. Cultured fibroblasts infected with DMV were incubated with lymphocytes isolated from the blood of human immune subjects. Rosettes defined by the adherence of three or more lymphocytes around a fibroblast were formed in infected preparation while no rosettes were seen with normal control fibroblasts. Approximately 1.2 per cent of lymphocytes were involved in the formation of these rosettes. Rosette formation is inhibited when infected fibroblasts have been incubated with anti-CMV antibodies prior to the addition of lymphocytes."}
{"id": "PMID:199365", "title": "[15 new serotypes of Salmonella of subgenus I isolated in Africa].", "content": "Filteen new serotypes of Salmonella belonging to the sub-genus I have been isolated in Africa. Isolated in Ivory Coast: S. dabou (8,20:Z4,Z23,l,W), S. elokate (9,12:c:1,7), S. assinie (3,10:1,w:Z5), S. anna (13,23:Z35:e,n,Z16), S. mpouto (16:m,t:-), S. banco (28:r:1,7), S. abidjan (38:b:l,w); in Senegal: S. bignona (17:b:e,n,Z15), S. lode (17:r:1,2), S. derkle (52,e,h:1,7); in Tchad: S. moussoro (1,6,14,25:i:e,n,Z15), S. drogana (1,4,12,27:r,i:e,n,Z15); in Algeria: S. hydra (21:c:1,6); in Haute-Volta S. farakan (28:Z10:1,5); in Republique Centrafricaine: S. babili (28:Z35:1,7).", "contents": "[15 new serotypes of Salmonella of subgenus I isolated in Africa]. Filteen new serotypes of Salmonella belonging to the sub-genus I have been isolated in Africa. Isolated in Ivory Coast: S. dabou (8,20:Z4,Z23,l,W), S. elokate (9,12:c:1,7), S. assinie (3,10:1,w:Z5), S. anna (13,23:Z35:e,n,Z16), S. mpouto (16:m,t:-), S. banco (28:r:1,7), S. abidjan (38:b:l,w); in Senegal: S. bignona (17:b:e,n,Z15), S. lode (17:r:1,2), S. derkle (52,e,h:1,7); in Tchad: S. moussoro (1,6,14,25:i:e,n,Z15), S. drogana (1,4,12,27:r,i:e,n,Z15); in Algeria: S. hydra (21:c:1,6); in Haute-Volta S. farakan (28:Z10:1,5); in Republique Centrafricaine: S. babili (28:Z35:1,7)."}
{"id": "PMID:199371", "title": "[Role of acoustic stress on the development of polyoma tumors in immunized golden hamsters].", "content": "An acoustic stress increases the metastatic spread of polyoma virus-induced tumors in syrian Hamsters. To try to elucidate the mechanism of this action, we studied the effect of stress on the protection afforded by the virus against tumour challenge. Exposure to ultrasonics during the immunization period markedly decreased the protective effect of the virus.", "contents": "[Role of acoustic stress on the development of polyoma tumors in immunized golden hamsters]. An acoustic stress increases the metastatic spread of polyoma virus-induced tumors in syrian Hamsters. To try to elucidate the mechanism of this action, we studied the effect of stress on the protection afforded by the virus against tumour challenge. Exposure to ultrasonics during the immunization period markedly decreased the protective effect of the virus."}
{"id": "PMID:199372", "title": "[Ultrastructural aspects of the cell fusion induced by Visna virus on sheep choroid plexus cell in culture].", "content": "Sheep choroid plexus cells infected with low multiplicities of infection of Visna Virus were stellate and had long and thin processes containing filaments and forming cytoplasmic bridges between adjacent cells. Enlargement of the bridges resulted in the formation of multinucleated cells. Some glycoproteins were clustered on filaments outside the cell. The cytoplasmic changes showed : an intensive protein synthesis; numerous mitochondria closely associated with filaments and some lysosomes and numerous vesicules near the plasma membrane.", "contents": "[Ultrastructural aspects of the cell fusion induced by Visna virus on sheep choroid plexus cell in culture]. Sheep choroid plexus cells infected with low multiplicities of infection of Visna Virus were stellate and had long and thin processes containing filaments and forming cytoplasmic bridges between adjacent cells. Enlargement of the bridges resulted in the formation of multinucleated cells. Some glycoproteins were clustered on filaments outside the cell. The cytoplasmic changes showed : an intensive protein synthesis; numerous mitochondria closely associated with filaments and some lysosomes and numerous vesicules near the plasma membrane."}
{"id": "PMID:199373", "title": "[Oxidation of malate, NADH and glycine in C3 and C4 plant mitochondria].", "content": "Spinach leaf mitochondria (C3 plant) were capable of oxidizing Glycine. This oxidation was linked to the mitochondrial electron transport chain, was coupled to three phosphorylation sites and was sensitive to electron transport inhibitors. In marked contrast however, neither mitochondria from dark grown plants nor mitochondria from C4 leaf plants were capable of oxidizing this amino acid.", "contents": "[Oxidation of malate, NADH and glycine in C3 and C4 plant mitochondria]. Spinach leaf mitochondria (C3 plant) were capable of oxidizing Glycine. This oxidation was linked to the mitochondrial electron transport chain, was coupled to three phosphorylation sites and was sensitive to electron transport inhibitors. In marked contrast however, neither mitochondria from dark grown plants nor mitochondria from C4 leaf plants were capable of oxidizing this amino acid."}
{"id": "PMID:199374", "title": "[Early effect of poliomyelitis virus on 5'-nucleotidase activity in HeLa cells].", "content": "One of the earlier effects of poliovirus was the maintaining of a high level of Hela cells 5'-nucleotidase activity (maximal efficiency for a virus/cell ratio = 500 ID 50/cell) (ID50:50% Infections Dose). The activity decreased when cells were suspended in the presence of EDTA(EDTA:Ethylene Diamine Tetracetic Acid) and was partially restored by adding 10 mM Mg++ interactions are discussed.", "contents": "[Early effect of poliomyelitis virus on 5'-nucleotidase activity in HeLa cells]. One of the earlier effects of poliovirus was the maintaining of a high level of Hela cells 5'-nucleotidase activity (maximal efficiency for a virus/cell ratio = 500 ID 50/cell) (ID50:50% Infections Dose). The activity decreased when cells were suspended in the presence of EDTA(EDTA:Ethylene Diamine Tetracetic Acid) and was partially restored by adding 10 mM Mg++ interactions are discussed."}
{"id": "PMID:199375", "title": "[Effect of the inhibition of \"NADH-diaphorase\" activity on the ultrastructural localization of 3 beta-hydroxysteroid dehydrogenase].", "content": "The NADH-ferricyanide oxidoreductase (\"NADH-diaphorase\") activity can be inhibited selectively with 0.5 mM p-chloromercuribenzoate, and the reduction of the potassium ferricyanide can be restored with an exogenous electron carrier (PMS). These operations do not affect the localization of the final precipitate of copper ferrocyanide which results from 3beta-hydroxysteroid dehydrogenase activity.", "contents": "[Effect of the inhibition of \"NADH-diaphorase\" activity on the ultrastructural localization of 3 beta-hydroxysteroid dehydrogenase]. The NADH-ferricyanide oxidoreductase (\"NADH-diaphorase\") activity can be inhibited selectively with 0.5 mM p-chloromercuribenzoate, and the reduction of the potassium ferricyanide can be restored with an exogenous electron carrier (PMS). These operations do not affect the localization of the final precipitate of copper ferrocyanide which results from 3beta-hydroxysteroid dehydrogenase activity."}
{"id": "PMID:199376", "title": "[Tissue antagonist of interferon : murine substance similar to plant lectins].", "content": "A tissue antagonist of interferon (TAI) extracted from mouse costal cartilage contains a substance which has many properties characteristic of plant lectins. After binding to the cell membrane receptors, it agglutines normal and transformed murine cells. In interferon treated cells, it restores virus sensitivity probably through a modification in the distribution of membrane bound cellular antigens.", "contents": "[Tissue antagonist of interferon : murine substance similar to plant lectins]. A tissue antagonist of interferon (TAI) extracted from mouse costal cartilage contains a substance which has many properties characteristic of plant lectins. After binding to the cell membrane receptors, it agglutines normal and transformed murine cells. In interferon treated cells, it restores virus sensitivity probably through a modification in the distribution of membrane bound cellular antigens."}
{"id": "PMID:199377", "title": "New micromethod for measuring cholesterol in plasma lipoprotein fractions.", "content": "A method is described for the reliable, fast, and relatively inexpensive fractionation of plasma lipoproteins and quantitation of their cholesterol content. This procedure requires 350 microliter of plasma and can be completed within 3 h. Plasma lipoproteins (175 microliter of plasma) were prestained with Fat Red 7B and centrifuged (Beckman Airfuge) at plasma density (d = 1.006 kg/liter) and at a solvent density of 1.060 kg/liter, adjusted by adding solid KBr. Prestained centrifuged samples demonstrated the characteristic elevation of chylomicrons in phenotypes I and V, low-density lipoproteins of phenotype II, very-low-density lipoproteins in phenotype IV and V, and continuum of pink color throughout the centrifuge tube, diagnostic of the floating beta lipoprotein of type III. Centrifuged samples were separated into top and bottom fractions by aspiration. Cholesterol was quantitated with an enzymic oxygen-electrode analyzer (Beckman Cholesterol Analyzer). Correlation coefficients between cholesterol values for plasma from normal hyperlipidemic individuals obtained with the Beckman Analyzer vs. the Technicon AutoAnalyzer II and SMAC systems were 0.977 and 0.973, respectively.", "contents": "New micromethod for measuring cholesterol in plasma lipoprotein fractions. A method is described for the reliable, fast, and relatively inexpensive fractionation of plasma lipoproteins and quantitation of their cholesterol content. This procedure requires 350 microliter of plasma and can be completed within 3 h. Plasma lipoproteins (175 microliter of plasma) were prestained with Fat Red 7B and centrifuged (Beckman Airfuge) at plasma density (d = 1.006 kg/liter) and at a solvent density of 1.060 kg/liter, adjusted by adding solid KBr. Prestained centrifuged samples demonstrated the characteristic elevation of chylomicrons in phenotypes I and V, low-density lipoproteins of phenotype II, very-low-density lipoproteins in phenotype IV and V, and continuum of pink color throughout the centrifuge tube, diagnostic of the floating beta lipoprotein of type III. Centrifuged samples were separated into top and bottom fractions by aspiration. Cholesterol was quantitated with an enzymic oxygen-electrode analyzer (Beckman Cholesterol Analyzer). Correlation coefficients between cholesterol values for plasma from normal hyperlipidemic individuals obtained with the Beckman Analyzer vs. the Technicon AutoAnalyzer II and SMAC systems were 0.977 and 0.973, respectively."}
{"id": "PMID:199378", "title": "The effect of temperature on the kinetic constants of human lactate dehydrogenase 1 and 5.", "content": "The kinetic constants of human lactate dehydrogenase 1 and 5 (L-lactate: NAD+ oxidoreductase, EC 1.1.1.27), assayed lactate-to-pyruvate increase with temperature. The reaction mechanism is ordered sequential as has been found with lactate dehydrogenase from other sources. The KM values for each substrate are larger for isoenzyme 5 than for 1. For lactate dehydrogenase 1 the KM(lactate) increases from 1.07 mM at 25 degrees C to 3.95 mM at 37 degrees C and for lactate dehydrogenase 5 it increases from 5.37 mM at 25 degrees C to 6.88 mM at 37 degrees C. The KM(NAD+) for lactate dehydrogenase 5 is 0.14 mM at 25 degrees C and 0.29 mM at 37 degrees C. The increase in the KM for each substrate with increasing temperature confirms that additional substrate is required for optimal reaction conditions at higher temperatures.", "contents": "The effect of temperature on the kinetic constants of human lactate dehydrogenase 1 and 5. The kinetic constants of human lactate dehydrogenase 1 and 5 (L-lactate: NAD+ oxidoreductase, EC 1.1.1.27), assayed lactate-to-pyruvate increase with temperature. The reaction mechanism is ordered sequential as has been found with lactate dehydrogenase from other sources. The KM values for each substrate are larger for isoenzyme 5 than for 1. For lactate dehydrogenase 1 the KM(lactate) increases from 1.07 mM at 25 degrees C to 3.95 mM at 37 degrees C and for lactate dehydrogenase 5 it increases from 5.37 mM at 25 degrees C to 6.88 mM at 37 degrees C. The KM(NAD+) for lactate dehydrogenase 5 is 0.14 mM at 25 degrees C and 0.29 mM at 37 degrees C. The increase in the KM for each substrate with increasing temperature confirms that additional substrate is required for optimal reaction conditions at higher temperatures."}
{"id": "PMID:199379", "title": "Urinary pregnanetriol excretion in hirsutism.", "content": "Eighteen consecutive hirsute women attending an endocrine clinic have been studied by measurement of the urinary pregnanetriol excretion before and following the concurrent administration of corticotrophin and metyrapone. An abnormal increment in pregnanetriol excretion was observed in 11 of these 18 patients. It is suggested that this is evidence that an adrenal abnormality, probably operative at the 21-hydroxylase level, might be a factor responsible for the hirsutism in these 11 patients. Five adrenalectomized women who were also studied showed no significant increase in urinary pregnanetriol excretion in response to concurrent corticotrophin and metyrapone administration.", "contents": "Urinary pregnanetriol excretion in hirsutism. Eighteen consecutive hirsute women attending an endocrine clinic have been studied by measurement of the urinary pregnanetriol excretion before and following the concurrent administration of corticotrophin and metyrapone. An abnormal increment in pregnanetriol excretion was observed in 11 of these 18 patients. It is suggested that this is evidence that an adrenal abnormality, probably operative at the 21-hydroxylase level, might be a factor responsible for the hirsutism in these 11 patients. Five adrenalectomized women who were also studied showed no significant increase in urinary pregnanetriol excretion in response to concurrent corticotrophin and metyrapone administration."}
{"id": "PMID:199380", "title": "How to collect blood for the measurement of HGH, LH, FSH, cyclic AMP, folic acid, cortisol and testosterone.", "content": "In order to estimate peptide hormones, steroid hormones, folic acid and cyclic AMP in the same blood sample we investigated the influences of different anticoagulants on the measurement. It could be demonstrated that blood collected in EDTA-coated tubes can be for the measurement of each of the mentioned constituents.", "contents": "How to collect blood for the measurement of HGH, LH, FSH, cyclic AMP, folic acid, cortisol and testosterone. In order to estimate peptide hormones, steroid hormones, folic acid and cyclic AMP in the same blood sample we investigated the influences of different anticoagulants on the measurement. It could be demonstrated that blood collected in EDTA-coated tubes can be for the measurement of each of the mentioned constituents."}
{"id": "PMID:199381", "title": "Changes in serum high density lipoproteins in women on oral contraceptive drugs.", "content": "Serum lipids, lipoproteins, and lipoprotein subfractions were measured in a group of 18 women aged 20 through 39 who were users of oral contraceptive drugs, and in 19 age-matched controls. Concentrations of the major lipid and lipoprotein classes were higher in the users, but the elevation was statistically significant only in the case of the high density lipoproteins. This increase was shown to be due to a highly significant increase (275 +/- 9 vs. 223 +/- 9 mg/100 ml, (p less than 0.005) in the denser high density lipoprotein subfraction (HDL3). Levels of the other subfraction (HDL2) were similar in users and controls. Thus, anovulatory steroids have selective effects on individual types of high density lipoproteins. Studies of such specific effects may help to further define the functional properties of the high density lipoproteins such as their apparent protective role in atherosclerosis.", "contents": "Changes in serum high density lipoproteins in women on oral contraceptive drugs. Serum lipids, lipoproteins, and lipoprotein subfractions were measured in a group of 18 women aged 20 through 39 who were users of oral contraceptive drugs, and in 19 age-matched controls. Concentrations of the major lipid and lipoprotein classes were higher in the users, but the elevation was statistically significant only in the case of the high density lipoproteins. This increase was shown to be due to a highly significant increase (275 +/- 9 vs. 223 +/- 9 mg/100 ml, (p less than 0.005) in the denser high density lipoprotein subfraction (HDL3). Levels of the other subfraction (HDL2) were similar in users and controls. Thus, anovulatory steroids have selective effects on individual types of high density lipoproteins. Studies of such specific effects may help to further define the functional properties of the high density lipoproteins such as their apparent protective role in atherosclerosis."}
{"id": "PMID:199382", "title": "Isolation and characterization of lipoprotein-X from the pig.", "content": "In vitro incubation of pig bile with pig whole serum resulted in the formation of \"LP-X like\" material migrating towards the cathode on agar-gel electrophoresis. As in all other species studied so far, LP-X occurred also in the serum of bile duct ligated pigs, however, relatively late (48-72h) after the operation. In parallel, alterations of some serum parameters and of the protein-lipid composition of the different lipoporotein fractions were observed. While the electrophoretic behaviour, the protein-lipid and apoprotein composition of pig LP-X were comparable to those found in man, dog and rat, it sedimated in most instances at the density 1.063 g/ml.", "contents": "Isolation and characterization of lipoprotein-X from the pig. In vitro incubation of pig bile with pig whole serum resulted in the formation of \"LP-X like\" material migrating towards the cathode on agar-gel electrophoresis. As in all other species studied so far, LP-X occurred also in the serum of bile duct ligated pigs, however, relatively late (48-72h) after the operation. In parallel, alterations of some serum parameters and of the protein-lipid composition of the different lipoporotein fractions were observed. While the electrophoretic behaviour, the protein-lipid and apoprotein composition of pig LP-X were comparable to those found in man, dog and rat, it sedimated in most instances at the density 1.063 g/ml."}
{"id": "PMID:199387", "title": "Genetic study of hyperlipoproteinaemia types IV and V.", "content": "In a family, of which 32 members belonging to three generations could be examined, 21 subjects were normal, while 11 were affected by hyperlipoproteinaemia types IV and V or related biological disorders. Neither an autosomal dominant inheritance nor an autosomal recessive inheritance nor a multiple-type hyperlipoproteinaemia can unreservedly be accepted.", "contents": "Genetic study of hyperlipoproteinaemia types IV and V. In a family, of which 32 members belonging to three generations could be examined, 21 subjects were normal, while 11 were affected by hyperlipoproteinaemia types IV and V or related biological disorders. Neither an autosomal dominant inheritance nor an autosomal recessive inheritance nor a multiple-type hyperlipoproteinaemia can unreservedly be accepted."}
{"id": "PMID:199388", "title": "A family with syndactyly type II (synpolydactyly).", "content": "Syndactyly Type II is reported in eight members of a family in four generations. Affected individuals show two distinctive patterns of variation in the expression of the gene. Distortion of dermatoglyphic patterns is associated with the severe but not the mild manifestation of the malformation. The diagnostic significance of minimal features of the condition is discussed. Linkage data suggest that loci for Syndactyly II and for blood-group antigens ABO, MNSs, P, Rh and Kell are not closely linked.", "contents": "A family with syndactyly type II (synpolydactyly). Syndactyly Type II is reported in eight members of a family in four generations. Affected individuals show two distinctive patterns of variation in the expression of the gene. Distortion of dermatoglyphic patterns is associated with the severe but not the mild manifestation of the malformation. The diagnostic significance of minimal features of the condition is discussed. Linkage data suggest that loci for Syndactyly II and for blood-group antigens ABO, MNSs, P, Rh and Kell are not closely linked."}
{"id": "PMID:199393", "title": "Plasma concentration of pyridostigmine and effects in myastenia gravis.", "content": "The relation between the plasma concentration of pyridostigmine and its effects was studied in 5 patients with myasthenia gravis. In 4 patients with typical electromyographic decrement in the adductor pollicis, there was a positive correlation between the concentration  of pyridostigmine in plasma and the effect on neuromuscular transmission. The plasma concentration of pyridostigmine required to restore transmission to normal (as calculated from the regression line relating plasma concentration to neuromuscular function) varied over a 5-fold range, reflecting the variable severity of the disease. In another myasthenic patient with purely ocular symptoms, there was a significant correlation between the plasma concentration of the drug and the diameter of the palpebral fissure. It is suggested that the routine measurement of the plasma concentration of pyridostigmine may be of value in the management of myasthenia gravis. A method to calculate the optimal daily dose of pyridostigmine in individual myasthenic patients is described.", "contents": "Plasma concentration of pyridostigmine and effects in myastenia gravis. The relation between the plasma concentration of pyridostigmine and its effects was studied in 5 patients with myasthenia gravis. In 4 patients with typical electromyographic decrement in the adductor pollicis, there was a positive correlation between the concentration  of pyridostigmine in plasma and the effect on neuromuscular transmission. The plasma concentration of pyridostigmine required to restore transmission to normal (as calculated from the regression line relating plasma concentration to neuromuscular function) varied over a 5-fold range, reflecting the variable severity of the disease. In another myasthenic patient with purely ocular symptoms, there was a significant correlation between the plasma concentration of the drug and the diameter of the palpebral fissure. It is suggested that the routine measurement of the plasma concentration of pyridostigmine may be of value in the management of myasthenia gravis. A method to calculate the optimal daily dose of pyridostigmine in individual myasthenic patients is described."}
{"id": "PMID:199396", "title": "The passage of apoproteins from plasma lipoproteins into the lipoproteins of peripheral lymph in man.", "content": "1. The transport of apoprotein B from the lipoprotein of plasma into the lipoproteins of lymph draining the foot has been studied in four men with type III hyperlipoproteinaemia. 2. Three subjects were given autologous 125I-labelled very-low-density lipoprotein (VLDL) and 131I-labelled low-density lipoprotein (LDL) by intravenous injection; the fourth was given autologous 125I-labelled VLDL and 131I-labelled intermediate-density lipoprotein (IDL) plus LDL. 3. The 125I/131I ratios in serum and lymph apoprotein B, and the 125I and 131I specific radioactivities of apoprotein B in VLDL, IDL and LDL from serum and lymph, indicate that apoprotein B in the circulating VLDL can reach peripherallymph without the intermediacy of circulating LDL.", "contents": "The passage of apoproteins from plasma lipoproteins into the lipoproteins of peripheral lymph in man. 1. The transport of apoprotein B from the lipoprotein of plasma into the lipoproteins of lymph draining the foot has been studied in four men with type III hyperlipoproteinaemia. 2. Three subjects were given autologous 125I-labelled very-low-density lipoprotein (VLDL) and 131I-labelled low-density lipoprotein (LDL) by intravenous injection; the fourth was given autologous 125I-labelled VLDL and 131I-labelled intermediate-density lipoprotein (IDL) plus LDL. 3. The 125I/131I ratios in serum and lymph apoprotein B, and the 125I and 131I specific radioactivities of apoprotein B in VLDL, IDL and LDL from serum and lymph, indicate that apoprotein B in the circulating VLDL can reach peripherallymph without the intermediacy of circulating LDL."}
{"id": "PMID:199392", "title": "[Studies on the development and therapy of scoliosis].", "content": "Inadequately treated cases of scoliosis with deterioration were studied. Biomechanics and pathology are discussed. It has been observed that permanent lateral deviation of the vertebral column continues irreversibly if not treated in time. A study of the evolution of scoliosis in relation to vertebral growth is reported. It is followed by a description of therapeutic management based on fundamental factors: --aetiology, the severity of the deformity, bone age and potential deterioration. A series of cases treated conservatively and by surgical fixation is illustrated.", "contents": "[Studies on the development and therapy of scoliosis]. Inadequately treated cases of scoliosis with deterioration were studied. Biomechanics and pathology are discussed. It has been observed that permanent lateral deviation of the vertebral column continues irreversibly if not treated in time. A study of the evolution of scoliosis in relation to vertebral growth is reported. It is followed by a description of therapeutic management based on fundamental factors: --aetiology, the severity of the deformity, bone age and potential deterioration. A series of cases treated conservatively and by surgical fixation is illustrated."}
{"id": "PMID:199403", "title": "Pathological and therapeutic consequences of sleep loss: a review.", "content": "Until recently sleep deprivation has been studied from the point of view of determining whether or not it produces deleterious effects. Evidence, however, has begun to accumulate indicating that both REM deprivation and single night sleep deprivation may have antidepressant effects. Although beneficial effects are found primarily in endogenously depressed patients, variable results have been obtained in both \"endogenous\" and \"reactive\" depressions, suggesting that these diagnostic categories include biologically heterogeneous populations.", "contents": "Pathological and therapeutic consequences of sleep loss: a review. Until recently sleep deprivation has been studied from the point of view of determining whether or not it produces deleterious effects. Evidence, however, has begun to accumulate indicating that both REM deprivation and single night sleep deprivation may have antidepressant effects. Although beneficial effects are found primarily in endogenously depressed patients, variable results have been obtained in both \"endogenous\" and \"reactive\" depressions, suggesting that these diagnostic categories include biologically heterogeneous populations."}
{"id": "PMID:199405", "title": "Modification of glycoprotein residues as Ca2+ receptor sites after chronic ethanol exposure.", "content": "Previous studies have demonstrated that chronic low-dose administration of ethanol in the drinking fluid of rats produces an increase in content of calcium on synaptic membranes. In the present study, ethanol was studied in vitro and in vivo for its effects on Ca2+ binding to a high affinity receptor site on synaptic membranes. Ethanol (1-50 micrometer) significantly inhibits the binding of Ca2+ in non-competitive fashion, together with inhibiton of a cooperative mechanism for Ca2+ binding. Ruthenium red and neuraminidase were used to probe surface glycoprotein sites as receptors for Ca2+. Use of these probes together with ethanol in vitro or in vivo suggests that increases in Ca2+ receptor sites after chronic ethanol exposure are related to an increase in sialic acid exposure, possibly as a result of conformational changes in membrane protein. These findings are consistent with the hypothesis that chronic low-dose exposure to ethanol causes changes in proteins of synaptic membranes, which may in turn regulate the cellular adaptation to ethanol.", "contents": "Modification of glycoprotein residues as Ca2+ receptor sites after chronic ethanol exposure. Previous studies have demonstrated that chronic low-dose administration of ethanol in the drinking fluid of rats produces an increase in content of calcium on synaptic membranes. In the present study, ethanol was studied in vitro and in vivo for its effects on Ca2+ binding to a high affinity receptor site on synaptic membranes. Ethanol (1-50 micrometer) significantly inhibits the binding of Ca2+ in non-competitive fashion, together with inhibiton of a cooperative mechanism for Ca2+ binding. Ruthenium red and neuraminidase were used to probe surface glycoprotein sites as receptors for Ca2+. Use of these probes together with ethanol in vitro or in vivo suggests that increases in Ca2+ receptor sites after chronic ethanol exposure are related to an increase in sialic acid exposure, possibly as a result of conformational changes in membrane protein. These findings are consistent with the hypothesis that chronic low-dose exposure to ethanol causes changes in proteins of synaptic membranes, which may in turn regulate the cellular adaptation to ethanol."}
{"id": "PMID:199409", "title": "[Primary carcinoma of the liver and long-term administration of oral contraceptives followed by pregnancy (author's transl)].", "content": "A 32-year-old woman who had taken oral contraceptives for seven years, became pregnant after omitting the drug and had a normal child. Soon after a malignant hepatic tumour became apparent of which she died after three months. The tumour was a hepatocellular carcinoma, of low differentiation under the electron microscope. The tumour cells contained fibrils similar to alcoholic hyaline. A review of published reports suggests the possibility that the oral contraceptives and the hormonal influence of the pregnancy together played an important role in the development of the malignant tumour.", "contents": "[Primary carcinoma of the liver and long-term administration of oral contraceptives followed by pregnancy (author's transl)]. A 32-year-old woman who had taken oral contraceptives for seven years, became pregnant after omitting the drug and had a normal child. Soon after a malignant hepatic tumour became apparent of which she died after three months. The tumour was a hepatocellular carcinoma, of low differentiation under the electron microscope. The tumour cells contained fibrils similar to alcoholic hyaline. A review of published reports suggests the possibility that the oral contraceptives and the hormonal influence of the pregnancy together played an important role in the development of the malignant tumour."}
{"id": "PMID:199410", "title": "[Familial hypobetalipoproteinaemia and diabetes mellitus (author's transl)].", "content": "In a 60-year-old patient with manifest diabetes mellitus and in his 63-year-old brother with latent diabetes mellitus hypobeta-lipoproteinaemia was diagnosed. Cholesterol values were around 1,8 mmol/1 in whole serum samples. The LDL-cholesterol fraction was 1,04 mmol/1. The beta-lipoprotein band in the lipoprotein electrophoresis was markedly reduced. Apolipoprotein B measured by radial immuno-diffusion was about 30% of the normal for age. The components of LDL were normal. Values of hepatic triglyceride lipase and lipoprotein lipase in heparinised plasma were within the normal range. The simultaneous occurrence of hypobetalipoproteinaemia and diabetes mellitus is described here for the first time.", "contents": "[Familial hypobetalipoproteinaemia and diabetes mellitus (author's transl)]. In a 60-year-old patient with manifest diabetes mellitus and in his 63-year-old brother with latent diabetes mellitus hypobeta-lipoproteinaemia was diagnosed. Cholesterol values were around 1,8 mmol/1 in whole serum samples. The LDL-cholesterol fraction was 1,04 mmol/1. The beta-lipoprotein band in the lipoprotein electrophoresis was markedly reduced. Apolipoprotein B measured by radial immuno-diffusion was about 30% of the normal for age. The components of LDL were normal. Values of hepatic triglyceride lipase and lipoprotein lipase in heparinised plasma were within the normal range. The simultaneous occurrence of hypobetalipoproteinaemia and diabetes mellitus is described here for the first time."}
{"id": "PMID:199406", "title": "Relationship between levels of cyclic nucleotides and gamma-aminobutyric acid during ethanol withdrawal in rats.", "content": "Cyclic nucleotide and gamma-aminobutyric acid (GABA) levels were measured in four brain areas of control rats and rats undergoing ethanol withdrawal. Cyclic adenosine 3',5' monophosphate (cyclic AMP) was increased in the cerebral cortex and pons-medulla oblongata; cyclic guanosine 3',5'-monophosphate (cyclic GMP) was increased in the cerebellum and cerebral cortex; and GABA was decreased in the cerebellum, subcortex and pons-medulla oblongata. Individual values in withdrawn animals were correlated and subjected to a factor analysis. One of the common factors identified by this analysis was important for all but one of the levels which changed during ethanol withdrawal. Significant correlations of levels correlated with this factor included a negative correlation between cyclic GMP and GABA levels in the cerebellum, a positive correlation between cyclic GMP levels in the cerebellum and cyclic AMP levels in the pons-medulla oblongata and a positive correlation between cyclic AMP levels in the pons-medulla oblongata and cerebral cortex. These results indicate that multiple brain areas and neurotransmitters are involved in ethanol withdrawal.", "contents": "Relationship between levels of cyclic nucleotides and gamma-aminobutyric acid during ethanol withdrawal in rats. Cyclic nucleotide and gamma-aminobutyric acid (GABA) levels were measured in four brain areas of control rats and rats undergoing ethanol withdrawal. Cyclic adenosine 3',5' monophosphate (cyclic AMP) was increased in the cerebral cortex and pons-medulla oblongata; cyclic guanosine 3',5'-monophosphate (cyclic GMP) was increased in the cerebellum and cerebral cortex; and GABA was decreased in the cerebellum, subcortex and pons-medulla oblongata. Individual values in withdrawn animals were correlated and subjected to a factor analysis. One of the common factors identified by this analysis was important for all but one of the levels which changed during ethanol withdrawal. Significant correlations of levels correlated with this factor included a negative correlation between cyclic GMP and GABA levels in the cerebellum, a positive correlation between cyclic GMP levels in the cerebellum and cyclic AMP levels in the pons-medulla oblongata and a positive correlation between cyclic AMP levels in the pons-medulla oblongata and cerebral cortex. These results indicate that multiple brain areas and neurotransmitters are involved in ethanol withdrawal."}
{"id": "PMID:199411", "title": "[Demonstration of the agent of bovine viral diarrhea-mucosal disease (BVD/MD) in comparison between organ fluoresence freezing method and the direct cultivation in tissue culture].", "content": "Organs of 100 calves whose clinical symptoms indicated a BVD/MD viral infection have been examined in the laboratory by different methods on BVD/MD virus in order to compare the effectivity of the single test-systems. By inoculation of organ material into tissue culture from foetal calf kidneys and additional staining with swine-fever conjugate in the CCSC-system 59 calves were detected as BVD/MD virus carriers. Taking this result for comparative purposes equal to 100% there could be stated an effectivity of 73% by inoculation of tissue cultures and judging cpe instead of staining with fluorescent antibody as above. Only 34% reactions could be demonstrated by means of heterotypic immunofluorescence in organ tissues. For diagnostic purposes a combination of the easy and quick method of heterotypic immunofluorescence in organ tissues and a cultural virus isolation from organ material with additional immunofluorescence is recommended.", "contents": "[Demonstration of the agent of bovine viral diarrhea-mucosal disease (BVD/MD) in comparison between organ fluoresence freezing method and the direct cultivation in tissue culture]. Organs of 100 calves whose clinical symptoms indicated a BVD/MD viral infection have been examined in the laboratory by different methods on BVD/MD virus in order to compare the effectivity of the single test-systems. By inoculation of organ material into tissue culture from foetal calf kidneys and additional staining with swine-fever conjugate in the CCSC-system 59 calves were detected as BVD/MD virus carriers. Taking this result for comparative purposes equal to 100% there could be stated an effectivity of 73% by inoculation of tissue cultures and judging cpe instead of staining with fluorescent antibody as above. Only 34% reactions could be demonstrated by means of heterotypic immunofluorescence in organ tissues. For diagnostic purposes a combination of the easy and quick method of heterotypic immunofluorescence in organ tissues and a cultural virus isolation from organ material with additional immunofluorescence is recommended."}
{"id": "PMID:199407", "title": "Cyclic adenosine 3',5'-monophosphate, adenylate cyclase and physical dependence on ethanol: studies with tranylcypromine.", "content": "Tranylcypromine, a monoamine oxidase inhititor, was administered to rats during chronic ethanol treatment. The severity of the hyperactive withdrawal behavior observed upon removal of ethanol was, during the first 60 hours of treatment, similar in both ethanol and ethanol + tranylcypromine treated animals. However, after 84 hours of ethanol treatment, tranylcypromine slightly depressed the withdrawal severity. Rises in cerebral cortical cyclic adenosine 3',5'-monophosphate (cAMP) levels and adenylate cyclase activity associated with withdrawal behavior in ethanol-treated rats, though, were not observed. (Adenylate cyclase activity used throughout this paper refers to % conversion of 3H-adenine into 3H-cAMP). Based on this and previous data, a model invoking two neurochemical adaptations--one in adenylate cyclase and one, as yet, unknown-is proposed for the mechanism of physical dependence.", "contents": "Cyclic adenosine 3',5'-monophosphate, adenylate cyclase and physical dependence on ethanol: studies with tranylcypromine. Tranylcypromine, a monoamine oxidase inhititor, was administered to rats during chronic ethanol treatment. The severity of the hyperactive withdrawal behavior observed upon removal of ethanol was, during the first 60 hours of treatment, similar in both ethanol and ethanol + tranylcypromine treated animals. However, after 84 hours of ethanol treatment, tranylcypromine slightly depressed the withdrawal severity. Rises in cerebral cortical cyclic adenosine 3',5'-monophosphate (cAMP) levels and adenylate cyclase activity associated with withdrawal behavior in ethanol-treated rats, though, were not observed. (Adenylate cyclase activity used throughout this paper refers to % conversion of 3H-adenine into 3H-cAMP). Based on this and previous data, a model invoking two neurochemical adaptations--one in adenylate cyclase and one, as yet, unknown-is proposed for the mechanism of physical dependence."}
{"id": "PMID:199412", "title": "[3 gastrointestinal neoplasms in the dog].", "content": "In the last five years, 3 carcinomas of the intestine were found in a total of 1961 necropsies of dogs. One proved to be a primary gastric carcinoma situated in the area of the Curvatura minor, another a primary carcinoma of the ileocaecal valve and the third one a signet-cell carcinoma in the end of the jejunum. The morphological characteristics of the carcinomas are discussed.", "contents": "[3 gastrointestinal neoplasms in the dog]. In the last five years, 3 carcinomas of the intestine were found in a total of 1961 necropsies of dogs. One proved to be a primary gastric carcinoma situated in the area of the Curvatura minor, another a primary carcinoma of the ileocaecal valve and the third one a signet-cell carcinoma in the end of the jejunum. The morphological characteristics of the carcinomas are discussed."}
{"id": "PMID:199415", "title": "Characterization and follicle stimulating hormone activation of Sertoli cell cyclic AMP-dependent protein kinases.", "content": "The Sertoli cell of the rat testis contains two cytoplasmic forms of adenosine 3',5' monophosphate (cyclic AMP)-dependent protein kinase, designated as Peak I and Peak II, which change in relative proportion during Sertoli cell maturation. Peak I and Peak II differ in their subunit interaction. Thus, while the substrates, ATP and histone, affect cyclic AMP binding to Peak I, neither of these compounds affect the binding of cyclic AMP to the Peak II enzyme. The effects of cyclic AMP binding to Peak I appear to be due to the fact that histone and high ionic strength cause dissociation of the Peak I holoenzyme, whereas ATP stabilizes the holoenzyme complex against dissociation. The Peak II holoenzyme is not affected by either salt of histone and is only dissociated by cyclic AMP. Once dissociated, the subunits of Peak II will rapidly reassociate under low salt conditions whereas the subunits of Peak I will not reassociate. By utilizing the distinct properties of Peak I and Peak II, it is possible to demonstrate the activation of both Peak I and Peak II Sertoli cell protein kinase in response to FSH.", "contents": "Characterization and follicle stimulating hormone activation of Sertoli cell cyclic AMP-dependent protein kinases. The Sertoli cell of the rat testis contains two cytoplasmic forms of adenosine 3',5' monophosphate (cyclic AMP)-dependent protein kinase, designated as Peak I and Peak II, which change in relative proportion during Sertoli cell maturation. Peak I and Peak II differ in their subunit interaction. Thus, while the substrates, ATP and histone, affect cyclic AMP binding to Peak I, neither of these compounds affect the binding of cyclic AMP to the Peak II enzyme. The effects of cyclic AMP binding to Peak I appear to be due to the fact that histone and high ionic strength cause dissociation of the Peak I holoenzyme, whereas ATP stabilizes the holoenzyme complex against dissociation. The Peak II holoenzyme is not affected by either salt of histone and is only dissociated by cyclic AMP. Once dissociated, the subunits of Peak II will rapidly reassociate under low salt conditions whereas the subunits of Peak I will not reassociate. By utilizing the distinct properties of Peak I and Peak II, it is possible to demonstrate the activation of both Peak I and Peak II Sertoli cell protein kinase in response to FSH."}
{"id": "PMID:199416", "title": "Preparation and immunological characteristics of biologically active radioiodinated human calcitonin.", "content": "Synthetic human calcitonin (hCT) was radioiodinated by electrolysis and chloramine-T oxidation. The electrolytic method was adapted for practicable quantities of hormone and isotope with no loss in efficiency of labeling. The immunological characterisitcs of the two hormone preparations were nearly identical using four calcitonin antisera with specificities for the regions 17-21, 17-29, 28-29, and 29-32 of hCT, respectively. However, only the electrolytically-labeled preparation retained full ability to produce hypocalcemia in vivo and stimulate cyclic AMP production in kidney homogenates of the rat. In addition, the electrolytically-iodinated hormone remained nearly homogeneous during 104 days of storage and the specific activity as measured by radioimmunoassay remained constant during one half-life of the isotope. These studies demonstrate that electrolytic iodination of hCT results in a tracer which is immunochemically stable and biologically active.", "contents": "Preparation and immunological characteristics of biologically active radioiodinated human calcitonin. Synthetic human calcitonin (hCT) was radioiodinated by electrolysis and chloramine-T oxidation. The electrolytic method was adapted for practicable quantities of hormone and isotope with no loss in efficiency of labeling. The immunological characterisitcs of the two hormone preparations were nearly identical using four calcitonin antisera with specificities for the regions 17-21, 17-29, 28-29, and 29-32 of hCT, respectively. However, only the electrolytically-labeled preparation retained full ability to produce hypocalcemia in vivo and stimulate cyclic AMP production in kidney homogenates of the rat. In addition, the electrolytically-iodinated hormone remained nearly homogeneous during 104 days of storage and the specific activity as measured by radioimmunoassay remained constant during one half-life of the isotope. These studies demonstrate that electrolytic iodination of hCT results in a tracer which is immunochemically stable and biologically active."}
{"id": "PMID:199419", "title": "Studies on the mode of action of somatostatin on insulin secretion.", "content": "The effect of somatostatin on insulin release by incubated slices of rat pancreas was studied. Somatostatin inhibited insulin release induced by arginine/glucose (A/G), glucagon, glibenclamide, pentoxifyllin, 3',5'-adenosine monophosphate (cAMP), phentolamine, and KCl. When A/G was used as a stimulus, the quantial inhibitory effect of somatostatin was not neutralized by progressively increasing glucose concentrations. The alpha adrenergic blocking agent phentolamine, the phosphodiesterase inhibitors theophylline (10 mM) or pentoxifyllin (10 mM), and KCl partially reversed the inhibitory effect of somatostatin on A/G stimulation. The maximal reversal of somatostatin inhibition was obtained when the slices of pancreas were stimulated with A/G in the presence of the calcium ioniphore A23187 plus ATP. These results suggest that the inhibitory effect of somatostatin on insulin secretion could result from calcium translocation in pancreatic beta cells.", "contents": "Studies on the mode of action of somatostatin on insulin secretion. The effect of somatostatin on insulin release by incubated slices of rat pancreas was studied. Somatostatin inhibited insulin release induced by arginine/glucose (A/G), glucagon, glibenclamide, pentoxifyllin, 3',5'-adenosine monophosphate (cAMP), phentolamine, and KCl. When A/G was used as a stimulus, the quantial inhibitory effect of somatostatin was not neutralized by progressively increasing glucose concentrations. The alpha adrenergic blocking agent phentolamine, the phosphodiesterase inhibitors theophylline (10 mM) or pentoxifyllin (10 mM), and KCl partially reversed the inhibitory effect of somatostatin on A/G stimulation. The maximal reversal of somatostatin inhibition was obtained when the slices of pancreas were stimulated with A/G in the presence of the calcium ioniphore A23187 plus ATP. These results suggest that the inhibitory effect of somatostatin on insulin secretion could result from calcium translocation in pancreatic beta cells."}
{"id": "PMID:199421", "title": "Presence of corticotropin in human placenta: demonstration of in vitro synthesis.", "content": "Immunoassayable (I) and bioassayable (B) ACTH activity is present in extracts of extensively washed human placental tissue and dispersed viable trophoblasts (Tr). Similar concentrations (I) (1.7-2.7 ng/g) are present in term placentas from elective cesarian section or vaginal delivery and from plancentas obtained by prostaglandin-induced abortion at 12, 15 and 18 weeks of gestation. Oral dexamethasone (8-12 mg) administered over an 8-48 h period prior to delivery does not significantly alter placental ACTH content. B-ACTH concentrations are 31-40% of I-ACTH. Sephadex G-50 filtration of term placental homogenates demonstrates two I-ACTH peaks, one eluting in the void volume and the other eluting in the region of synthetic hACTH1-39. When Tr are incubated in tissue culture medium, ACTH content of cells and of medium is significantly greater than pre-incubation levels.", "contents": "Presence of corticotropin in human placenta: demonstration of in vitro synthesis. Immunoassayable (I) and bioassayable (B) ACTH activity is present in extracts of extensively washed human placental tissue and dispersed viable trophoblasts (Tr). Similar concentrations (I) (1.7-2.7 ng/g) are present in term placentas from elective cesarian section or vaginal delivery and from plancentas obtained by prostaglandin-induced abortion at 12, 15 and 18 weeks of gestation. Oral dexamethasone (8-12 mg) administered over an 8-48 h period prior to delivery does not significantly alter placental ACTH content. B-ACTH concentrations are 31-40% of I-ACTH. Sephadex G-50 filtration of term placental homogenates demonstrates two I-ACTH peaks, one eluting in the void volume and the other eluting in the region of synthetic hACTH1-39. When Tr are incubated in tissue culture medium, ACTH content of cells and of medium is significantly greater than pre-incubation levels."}
{"id": "PMID:199422", "title": "Cyclic AMP production in rat calvaria in vitro: interaction prostaglandins with parathyroid hormone.", "content": "We studied the cAMP response of cultured rat calvaria to parathyroid hormone (PTH) and prostaglandins (PG) in order to test the hypothesis that PTH action is mediated by PG. PTH and PGE1 each caused an 8-fold increase in tissue cAMP during 15 min incubation. There was an additive response to the combination of the two agonists at maximally effective individual concentrations. Similar results were obtained when adenylate cyclase activity in bone homogenates were measured. Calvaria incubated for 60 min with PGE1 were desensitized to further stimulation by PGE1, but responded normally to PTH. Indomethacin, aspirin and phenylbutazone, 10(-5)M, had no effect on the cAMP response to PTH. At millimolar concentration these agents did block the hormone response; however, the response to exogenous PGE1 and the fluoride-sensitive adenylate cyclase were also inhibited. Thus, it appears that the effects of high concentrations of the anti-inflammatory drugs on cAMP formation are non-specific. Our results suggest that receptors in bone for PTH and prostaglandins are separate and independent, and that the cAMP response to PTH is not mediated by prostaglandins.", "contents": "Cyclic AMP production in rat calvaria in vitro: interaction prostaglandins with parathyroid hormone. We studied the cAMP response of cultured rat calvaria to parathyroid hormone (PTH) and prostaglandins (PG) in order to test the hypothesis that PTH action is mediated by PG. PTH and PGE1 each caused an 8-fold increase in tissue cAMP during 15 min incubation. There was an additive response to the combination of the two agonists at maximally effective individual concentrations. Similar results were obtained when adenylate cyclase activity in bone homogenates were measured. Calvaria incubated for 60 min with PGE1 were desensitized to further stimulation by PGE1, but responded normally to PTH. Indomethacin, aspirin and phenylbutazone, 10(-5)M, had no effect on the cAMP response to PTH. At millimolar concentration these agents did block the hormone response; however, the response to exogenous PGE1 and the fluoride-sensitive adenylate cyclase were also inhibited. Thus, it appears that the effects of high concentrations of the anti-inflammatory drugs on cAMP formation are non-specific. Our results suggest that receptors in bone for PTH and prostaglandins are separate and independent, and that the cAMP response to PTH is not mediated by prostaglandins."}
{"id": "PMID:199424", "title": "Testicular binding of 125I-HCG in developing estrogenized and androgenized rats.", "content": "The present work describes changes seen in the binding of 125I-HCG by testis homogenates of rats injected at the age of three days with 400 microgram estradiol-17beta-dipropionate, or 250 microgram testosterone propionate. Estrogenized and androgenized male rats showed a marked decrease of gonadotropin binding in testis at the 30th, 45th and 60th postnatal day. These results show that delayed sexual maturation of male rats treated with estrogen and androgen in the neonatal period is also related to pubertal decrease of testicular gonadotropin receptors.", "contents": "Testicular binding of 125I-HCG in developing estrogenized and androgenized rats. The present work describes changes seen in the binding of 125I-HCG by testis homogenates of rats injected at the age of three days with 400 microgram estradiol-17beta-dipropionate, or 250 microgram testosterone propionate. Estrogenized and androgenized male rats showed a marked decrease of gonadotropin binding in testis at the 30th, 45th and 60th postnatal day. These results show that delayed sexual maturation of male rats treated with estrogen and androgen in the neonatal period is also related to pubertal decrease of testicular gonadotropin receptors."}
{"id": "PMID:199426", "title": "Studies on protein-phosphorylation reactions in isolated chromatin.", "content": "The endogenous protein-phosphorylating activity of isolated chromatin was tested. We have found that a group of high-molecular-weight proteins (Mr greater than 50 000) was preferentially phosphorylated when chromatin from mouse ascites cells or from bovine lymphocytes was incubated in the presence of ATP. After disintegration of chromatin by nuclease treatment or by high salt concentration, a larger spectrum of chromatin proteins becomes accessible for phosphorylation by the chromatin-bound protein kinase. Some observations described in this communication may help to partially explain this result. The protein kinase was not found in nucleosomal subunits, indicating a non-random distribution of the enzyme in chromatin. This suggests that enzyme and substrate have to be in close spatial contact for the phosphorylation reaction to occur. Furthermore, we have shown for one protein, histone H1, that phosphorylation sites for the endogenous protein kinase are available on the free but not on the DNA-bound protein, suggesting that phosphate-accepting sites in chromatin proteins may be blocked by protein-DNA or by protein-protein interactions. We also discuss the possibility that chromatin protein kinase occurs in stable complexes with its phosphate-accepting substrates, as has been suggested by the findings of other [Kish, V.M. & Kleinsmith, L.J. (1974) J. Biol. Chem. 249, 750-760].", "contents": "Studies on protein-phosphorylation reactions in isolated chromatin. The endogenous protein-phosphorylating activity of isolated chromatin was tested. We have found that a group of high-molecular-weight proteins (Mr greater than 50 000) was preferentially phosphorylated when chromatin from mouse ascites cells or from bovine lymphocytes was incubated in the presence of ATP. After disintegration of chromatin by nuclease treatment or by high salt concentration, a larger spectrum of chromatin proteins becomes accessible for phosphorylation by the chromatin-bound protein kinase. Some observations described in this communication may help to partially explain this result. The protein kinase was not found in nucleosomal subunits, indicating a non-random distribution of the enzyme in chromatin. This suggests that enzyme and substrate have to be in close spatial contact for the phosphorylation reaction to occur. Furthermore, we have shown for one protein, histone H1, that phosphorylation sites for the endogenous protein kinase are available on the free but not on the DNA-bound protein, suggesting that phosphate-accepting sites in chromatin proteins may be blocked by protein-DNA or by protein-protein interactions. We also discuss the possibility that chromatin protein kinase occurs in stable complexes with its phosphate-accepting substrates, as has been suggested by the findings of other [Kish, V.M. & Kleinsmith, L.J. (1974) J. Biol. Chem. 249, 750-760]."}
{"id": "PMID:199427", "title": "The isolation of tubulin and actin from mouse 3T3 cells transformed by simian virus 40 (SV3T3 cells), an established cell line growing in culture.", "content": "Tubulin can be purified from mouse SV3T3 cells (3T3 cells transformed by SV40 virus) by several cycles of temperature-dependent polymerization and depolymerization. Electron microscopical analysis of the final product reveals morphologically normal microtubules. Homogeneous actin can be isolated as a byproduct of the purification procedure. Mouse SV3T3 actin and skeletal muscle actin were compared by fingerprint analysis of the tryptic peptides obtained from performic-acid-oxidized protein. The two actins show a high degree of homology although apparently five of the twenty-five spots visualized by fluorescamine show a difference in chromatographic mobility. The purification procedure described allows the rapid isolation of both actin and tubulin from tissue culture in sufficient amounts for comparative biochemicals studies.", "contents": "The isolation of tubulin and actin from mouse 3T3 cells transformed by simian virus 40 (SV3T3 cells), an established cell line growing in culture. Tubulin can be purified from mouse SV3T3 cells (3T3 cells transformed by SV40 virus) by several cycles of temperature-dependent polymerization and depolymerization. Electron microscopical analysis of the final product reveals morphologically normal microtubules. Homogeneous actin can be isolated as a byproduct of the purification procedure. Mouse SV3T3 actin and skeletal muscle actin were compared by fingerprint analysis of the tryptic peptides obtained from performic-acid-oxidized protein. The two actins show a high degree of homology although apparently five of the twenty-five spots visualized by fluorescamine show a difference in chromatographic mobility. The purification procedure described allows the rapid isolation of both actin and tubulin from tissue culture in sufficient amounts for comparative biochemicals studies."}
{"id": "PMID:199428", "title": "Purification and primary structure of cytochrome f from the cyanobacterium, Plectonema boryanum.", "content": "The amino acid sequence of the soluble c-type cytochrome, cytochrome f, from the cyanobacterium Plectonema boryanum (also called Phormidium luridum or Schizothrix calcicola) has been determined. The proposed sequence consists of one polypeptide chain of 85 residues and has three Asn-Gly linkages. Partly due to the presence of these Asn-Gly bonds, which readily undergo rearrangement, proteolytic digestion on the small amount of protein available was unsatisfactory. The structure was determined partly by a combination of chemical cleavage and automatic sequencing techniques. A new technique for conserving material by cyanogen bromide cleavage of residual polypeptide after automatic degradation is described. The possible evolutionary significance of primary structure comparisons with other cytochromes f is discussed.", "contents": "Purification and primary structure of cytochrome f from the cyanobacterium, Plectonema boryanum. The amino acid sequence of the soluble c-type cytochrome, cytochrome f, from the cyanobacterium Plectonema boryanum (also called Phormidium luridum or Schizothrix calcicola) has been determined. The proposed sequence consists of one polypeptide chain of 85 residues and has three Asn-Gly linkages. Partly due to the presence of these Asn-Gly bonds, which readily undergo rearrangement, proteolytic digestion on the small amount of protein available was unsatisfactory. The structure was determined partly by a combination of chemical cleavage and automatic sequencing techniques. A new technique for conserving material by cyanogen bromide cleavage of residual polypeptide after automatic degradation is described. The possible evolutionary significance of primary structure comparisons with other cytochromes f is discussed."}
{"id": "PMID:199430", "title": "Induction of division synchrony in Tetrahymena pyriformis by a single hypoxic shock. Its use in elucidating control of the cell cycle by adenosine 3':5'-monophosphate.", "content": "A single hypoxic shock was used to induce division synchrony in Tetrahymena pyriformis. Hypoxia results in accumulation of the cells in the G2 phase of the cell cycle. Cyclic AMP and adenyl cyclase activity were measured in this system. Cell-cycle blockade was associated with extraordinarily high levels of intracellular cyclic AMP. After release from hypoxia, the cells retain a characteristic pattern of modulation of cyclic AMP associated with division that is found in selection-synchronized cells. The results are discussed with reference to other methods of induction synchrony and related studies on the natural cell cycle in this organism.", "contents": "Induction of division synchrony in Tetrahymena pyriformis by a single hypoxic shock. Its use in elucidating control of the cell cycle by adenosine 3':5'-monophosphate. A single hypoxic shock was used to induce division synchrony in Tetrahymena pyriformis. Hypoxia results in accumulation of the cells in the G2 phase of the cell cycle. Cyclic AMP and adenyl cyclase activity were measured in this system. Cell-cycle blockade was associated with extraordinarily high levels of intracellular cyclic AMP. After release from hypoxia, the cells retain a characteristic pattern of modulation of cyclic AMP associated with division that is found in selection-synchronized cells. The results are discussed with reference to other methods of induction synchrony and related studies on the natural cell cycle in this organism."}
{"id": "PMID:199433", "title": "Choline kinase and ethanolamine kinase are separate, soluble enzymes in rat liver.", "content": "Choline kinase and ethanolamine kinase are located in the cytosol from rat liver and have been copurified more than 500-fold by affinity chromatography [P. J. Brophy and D. E. Vance (1976) FEBS Lett. 62, 123-125]. Kinetic properties of the two activities were determined. Choline kinase had a Km for choline of 0.033 mM and ethanolamine was a competitive inhibitor (Ki = 6.2 mM). Ethanolamine kinase had a Km for ethanolamine of 7.7 mM and choline was a 'mixed' type of inhibitor with a Ki of 0.037 mM. Both enzymes activities responded in a similar fashion to the adenylate energy charge. Betaine and choline phosphate partially inhibited both kinases with a 93% inhibition of the ethanolamine kinase by 5 mM choline phosphate. CTP and ethanolaminephosphate partially inhibited the ethanolamine kinase, but not the choline kinase. Other metabolites tested had negliglible effects on both kinases. The affinity-column-purified enzyme was analyzed by disc gel electrophoresis which resolved the two activities. Hence, although many of the properties of the two activities are similar, choline kinase and ethanolamine kinase must be separate enzymes. Analysis of rat liver cytosol by disc gel electrophoresis indicated four isoenzymes for choline kinase and ethanolamine kinase.", "contents": "Choline kinase and ethanolamine kinase are separate, soluble enzymes in rat liver. Choline kinase and ethanolamine kinase are located in the cytosol from rat liver and have been copurified more than 500-fold by affinity chromatography [P. J. Brophy and D. E. Vance (1976) FEBS Lett. 62, 123-125]. Kinetic properties of the two activities were determined. Choline kinase had a Km for choline of 0.033 mM and ethanolamine was a competitive inhibitor (Ki = 6.2 mM). Ethanolamine kinase had a Km for ethanolamine of 7.7 mM and choline was a 'mixed' type of inhibitor with a Ki of 0.037 mM. Both enzymes activities responded in a similar fashion to the adenylate energy charge. Betaine and choline phosphate partially inhibited both kinases with a 93% inhibition of the ethanolamine kinase by 5 mM choline phosphate. CTP and ethanolaminephosphate partially inhibited the ethanolamine kinase, but not the choline kinase. Other metabolites tested had negliglible effects on both kinases. The affinity-column-purified enzyme was analyzed by disc gel electrophoresis which resolved the two activities. Hence, although many of the properties of the two activities are similar, choline kinase and ethanolamine kinase must be separate enzymes. Analysis of rat liver cytosol by disc gel electrophoresis indicated four isoenzymes for choline kinase and ethanolamine kinase."}
{"id": "PMID:199435", "title": "Inhibition of human erythrocyte lactate dehydrogenase by high concentrations of pyruvate. Evidence for the competitive substrate inhibition.", "content": "The mechanism of the inhibitory effect of high concentrations of pyruvate on human erythrocyte lactate dehydrogenase has been studied by the use of a new parameter, delta, defined as the difference between the reciprocals of initial reaction rates obtained from experimental measurements and hypothetical linear Lineweaver-Burk plots. This parameter served as a method for differentiating between the competitive and umcompetitive substrate inhibition. Results of this study indicate that pyruvate is a competitive substrate inhibitor. It is suggested that the inhibitory effect of pyruvate is due to its competition with  NADH for binding to the free enzyme and formation of an inactive enzyme-pyruvate binary complex. The competitive nature of pyruvate inhibition is further supported by the results of a kinetic study with NADH as the variable substrate. The dissociation constnat of the inactive enzyme-pyruvate binary complex was determined to be 101 micrometer. The physiological significance of the inhibitory effect could be to preserve a level of NADH concentration necessary for other vital enzymic reactions of living cells despite the presence of a high concentration of pyruvate.", "contents": "Inhibition of human erythrocyte lactate dehydrogenase by high concentrations of pyruvate. Evidence for the competitive substrate inhibition. The mechanism of the inhibitory effect of high concentrations of pyruvate on human erythrocyte lactate dehydrogenase has been studied by the use of a new parameter, delta, defined as the difference between the reciprocals of initial reaction rates obtained from experimental measurements and hypothetical linear Lineweaver-Burk plots. This parameter served as a method for differentiating between the competitive and umcompetitive substrate inhibition. Results of this study indicate that pyruvate is a competitive substrate inhibitor. It is suggested that the inhibitory effect of pyruvate is due to its competition with  NADH for binding to the free enzyme and formation of an inactive enzyme-pyruvate binary complex. The competitive nature of pyruvate inhibition is further supported by the results of a kinetic study with NADH as the variable substrate. The dissociation constnat of the inactive enzyme-pyruvate binary complex was determined to be 101 micrometer. The physiological significance of the inhibitory effect could be to preserve a level of NADH concentration necessary for other vital enzymic reactions of living cells despite the presence of a high concentration of pyruvate."}
{"id": "PMID:199436", "title": "Preparation of polypeptide subunits of cytochrome oxidase from Neurospora crassa.", "content": "Cytochrome oxidase was purified from Neurospora crassa by ammonium sulfate fractionation in the presence of bile salts. The enzyme preparations contained 10-13 nmol of heme a per mg of protein; no other hemoproteins could be detected. Dodecylsulfate gel electrophoresis resolved the enzyme complex into seven major bands, representing seven polypeptide subunits. A procedure is described that allows the isolation of these enzyme subunits on a large scale starting from a single batch of oxidase preparation. It involves dissociation of the enzyme complex by dodecylsulfate and subsequent separation of the obtained polypeptides by chromatography in the presence of various dodecylsulfate concentrations. Purification of subunits 3, 4, 5, 6 and 7 was achieved by column chromatography using molecular sieves (Sephadex G-100, Bio Gel P-60) and hydroxylapatite. For the purification of subunits 1 and 2 an electrophoretic separation on a preparative polyacrylamide gel was required. The advantages and disadvantages of the separation procedure of the enzyme polypeptides are discussed. As a special point of interest, the conservation of antigenic determinants of the polypeptide chains during the dodecylsulfate treatment is considered.", "contents": "Preparation of polypeptide subunits of cytochrome oxidase from Neurospora crassa. Cytochrome oxidase was purified from Neurospora crassa by ammonium sulfate fractionation in the presence of bile salts. The enzyme preparations contained 10-13 nmol of heme a per mg of protein; no other hemoproteins could be detected. Dodecylsulfate gel electrophoresis resolved the enzyme complex into seven major bands, representing seven polypeptide subunits. A procedure is described that allows the isolation of these enzyme subunits on a large scale starting from a single batch of oxidase preparation. It involves dissociation of the enzyme complex by dodecylsulfate and subsequent separation of the obtained polypeptides by chromatography in the presence of various dodecylsulfate concentrations. Purification of subunits 3, 4, 5, 6 and 7 was achieved by column chromatography using molecular sieves (Sephadex G-100, Bio Gel P-60) and hydroxylapatite. For the purification of subunits 1 and 2 an electrophoretic separation on a preparative polyacrylamide gel was required. The advantages and disadvantages of the separation procedure of the enzyme polypeptides are discussed. As a special point of interest, the conservation of antigenic determinants of the polypeptide chains during the dodecylsulfate treatment is considered."}
{"id": "PMID:199437", "title": "Protein components of very low density lipoproteins from hen's egg yolk.", "content": "Egg yolk lipoproteins of very low density were found to contain proteins with cofactor activity for lipoprotein lipase. When delipidated very low density lipoproteins were dissolved in 10 mM HCl and fractionated by gel filtration about two thirds of the protein were in several components with estimated molecular weights of 60000 to more than 170000. The major low-molecular-weight proteins were the dimeric and monomeric forms of a previously characterized 9000-dalton peptide. The cofactor activity was not associated with any of these major proteins. A large-scale fractionation method was developed by which two proteins fractions with cofactor activity for lipoprotein lipase were purified more than thousand-fold. One fraction had a molecular size of about 9000 daltons and the other had a size of about 5000 daltons. Both these fractions could be further separated on the basis of charge into several fractions with cofactor activity. The cofactor proteins were relatively soluble both at high and at low pH. The retained their cofactor activity after denaturation in guanidinium hydrochloride and after reduction. During the initial steps in the purification of the cofactor proteins another low-molecular-weight protein followed the cofactors. It had a single 17500-dalton peptide chain and was present in four variants, three of which contained carbohydrate.", "contents": "Protein components of very low density lipoproteins from hen's egg yolk. Egg yolk lipoproteins of very low density were found to contain proteins with cofactor activity for lipoprotein lipase. When delipidated very low density lipoproteins were dissolved in 10 mM HCl and fractionated by gel filtration about two thirds of the protein were in several components with estimated molecular weights of 60000 to more than 170000. The major low-molecular-weight proteins were the dimeric and monomeric forms of a previously characterized 9000-dalton peptide. The cofactor activity was not associated with any of these major proteins. A large-scale fractionation method was developed by which two proteins fractions with cofactor activity for lipoprotein lipase were purified more than thousand-fold. One fraction had a molecular size of about 9000 daltons and the other had a size of about 5000 daltons. Both these fractions could be further separated on the basis of charge into several fractions with cofactor activity. The cofactor proteins were relatively soluble both at high and at low pH. The retained their cofactor activity after denaturation in guanidinium hydrochloride and after reduction. During the initial steps in the purification of the cofactor proteins another low-molecular-weight protein followed the cofactors. It had a single 17500-dalton peptide chain and was present in four variants, three of which contained carbohydrate."}
{"id": "PMID:199440", "title": "DNA unwinding enzyme II of Escherichia coli. 1. Purification and characterization of the ATPase activity.", "content": "A DNA-stimulated ATP-gamma-phosphohydrolase of molecular weight 75000 was purified from Escherichia coli cells. The ATPase, a globular molecule (identical probably with an ATPase described previously by Richet and Kohiyama in 1976) shows specificity for adenine nucleotides, it prefers single-stranded DNA as the cofactor, it exhibits a complicated mode of response to variations of the cofacter concentration and it is devoid of nuclease activity. Preparations derived from rep3 mutant cells yield widely varying amounts of an apparently normal ATPase.", "contents": "DNA unwinding enzyme II of Escherichia coli. 1. Purification and characterization of the ATPase activity. A DNA-stimulated ATP-gamma-phosphohydrolase of molecular weight 75000 was purified from Escherichia coli cells. The ATPase, a globular molecule (identical probably with an ATPase described previously by Richet and Kohiyama in 1976) shows specificity for adenine nucleotides, it prefers single-stranded DNA as the cofactor, it exhibits a complicated mode of response to variations of the cofacter concentration and it is devoid of nuclease activity. Preparations derived from rep3 mutant cells yield widely varying amounts of an apparently normal ATPase."}
{"id": "PMID:199441", "title": "DNA unwinding enzyme II of Escherichia coli. 2. Characterization of the DNA unwinding activity.", "content": "The DNA-stimulated 75000-Mr ATPase described in the preceding paper is shown to be a further catalytic DNA unwinding principle (DNA unwinding enzyme II) made in Escherichia coli cells (the first being the 180000-Mr ATPase of the cells: DNA unwinding enzyme I). Unwinding depends strictly, on the supply of ATP. It occurs only under conditions permitting ATP dephosphorylation and it proceeds as long as enzyme molecules are permitted to enter the enzyme - DNA complex. The enzyme binds specifically to single-stranded DNA yielding a complex of only limited stability. These results are interpreted in terms of a distributive mode of action of the enzyme. It is argued that chain separation starts near a single-stranded DNA region and that, forced by continued adsorption of enzyme molecules to the DNA, it develops along the duplex. This mechanism is different from that deduced previously for DNA unwinding enzyme I. Complicated results were obtained using ATPase prepared from rep3 mutant cells.", "contents": "DNA unwinding enzyme II of Escherichia coli. 2. Characterization of the DNA unwinding activity. The DNA-stimulated 75000-Mr ATPase described in the preceding paper is shown to be a further catalytic DNA unwinding principle (DNA unwinding enzyme II) made in Escherichia coli cells (the first being the 180000-Mr ATPase of the cells: DNA unwinding enzyme I). Unwinding depends strictly, on the supply of ATP. It occurs only under conditions permitting ATP dephosphorylation and it proceeds as long as enzyme molecules are permitted to enter the enzyme - DNA complex. The enzyme binds specifically to single-stranded DNA yielding a complex of only limited stability. These results are interpreted in terms of a distributive mode of action of the enzyme. It is argued that chain separation starts near a single-stranded DNA region and that, forced by continued adsorption of enzyme molecules to the DNA, it develops along the duplex. This mechanism is different from that deduced previously for DNA unwinding enzyme I. Complicated results were obtained using ATPase prepared from rep3 mutant cells."}
{"id": "PMID:199443", "title": "Detection of hepatoma in liver cirrhosis.", "content": "The analogic liver scintigram using 99mTc sulfur colloid in cirrhotic patients does not permit determination of the nature of the areas of decreased uptake. Scintigrams with 67Ga citrate generally show increased activity in cases of hepatoma. In some cases, however, 67Ga citrate is less concentrated in neoplasic tissue, and it is not possible to detect a tumoral lesion in a cirrhotic liver. This is why we used double isotope scintigraphies with 67Ga citrate and 99mTc sulfur colloid, with digital subtraction, after simultaneous recording of 99mTc and 67Ga data on magnetic tape by means of an interface. In our series of 22 patients, the comparison of the results obtained by this double isotope technique with histology showed no false positive in substraction scintigrams. There was one false negative because of the lack of significance in the subtracted image for one of the six patients with cancer of the liver. For three of the six patients with hepatoma, the gallium scintigram showed an increased uptake in the tumor area. For the three other cases, the gallium uptake was equilibrated throughout the liver scintigraphy. It was therefore in cases where the gallium scintigram showed no increased activity that the subtraction technique was of greatest value, for it permitted the diagnosis of hepatoma in two cases.", "contents": "Detection of hepatoma in liver cirrhosis. The analogic liver scintigram using 99mTc sulfur colloid in cirrhotic patients does not permit determination of the nature of the areas of decreased uptake. Scintigrams with 67Ga citrate generally show increased activity in cases of hepatoma. In some cases, however, 67Ga citrate is less concentrated in neoplasic tissue, and it is not possible to detect a tumoral lesion in a cirrhotic liver. This is why we used double isotope scintigraphies with 67Ga citrate and 99mTc sulfur colloid, with digital subtraction, after simultaneous recording of 99mTc and 67Ga data on magnetic tape by means of an interface. In our series of 22 patients, the comparison of the results obtained by this double isotope technique with histology showed no false positive in substraction scintigrams. There was one false negative because of the lack of significance in the subtracted image for one of the six patients with cancer of the liver. For three of the six patients with hepatoma, the gallium scintigram showed an increased uptake in the tumor area. For the three other cases, the gallium uptake was equilibrated throughout the liver scintigraphy. It was therefore in cases where the gallium scintigram showed no increased activity that the subtraction technique was of greatest value, for it permitted the diagnosis of hepatoma in two cases."}
{"id": "PMID:199444", "title": "Apallic syndrome in chronic mercury poisoning.", "content": "This report includes five cases afflicted by chronic mercury poisoning which was observed in Iraq in 1972. All five cases showed the symptomatology of a severe cerebral damage combined with peripheral nerve lesion. The clinical picture reveals an apallic syndrome or a prestage ensuring in the full-blown picture. The combination of CNS lesions with polyneuropathy is typical of mercury poisoning with failure of all brain functions and the appearance of brain stem automatism, combined with severe muscular atrophy. When such conditions are established the remission seems to be impossible. The historical as well as the clinical and morphological facts of the Minamata disease is reviewed. The different stages of chronic mercury poisoning in Iraq are described.", "contents": "Apallic syndrome in chronic mercury poisoning. This report includes five cases afflicted by chronic mercury poisoning which was observed in Iraq in 1972. All five cases showed the symptomatology of a severe cerebral damage combined with peripheral nerve lesion. The clinical picture reveals an apallic syndrome or a prestage ensuring in the full-blown picture. The combination of CNS lesions with polyneuropathy is typical of mercury poisoning with failure of all brain functions and the appearance of brain stem automatism, combined with severe muscular atrophy. When such conditions are established the remission seems to be impossible. The historical as well as the clinical and morphological facts of the Minamata disease is reviewed. The different stages of chronic mercury poisoning in Iraq are described."}
{"id": "PMID:199451", "title": "Ascending vestibular projections: further results at cortical and thalamic levels in the cat.", "content": "The purpose of this work was to precisely delineate the vestibular projection area in the cat's cortex and to trace electrophysiologically its afferent pathways at thalamic and mesencephalic levels. On anaesthetized animals, macropotentials evoked by electrical stimulation of the ampullar nerve from the horizontal semi-circular canal were recorded at three levels: on the cortex, the vestibular zone is restricted to the lower lip of the suprasylvian gyrus; in the thalamus, our results demonstrate the vestibular character of the magnocellular part of the medial geniculate body; at the mesencephalic level, our recordings indicate the existence of an ascending vestibular pathway situated laterally and ventrally with respect to the medial longitudinal bundle. The discussion focuses on two main points: 1. the precise cortical projection area of the horizontal ampullar nerve in relation to cytoarchitectonic areas and its possible functional role in motor programming. 2. the thalamic relays of the vestibulo-cortical pathway with regard to the hypothesis of two parallel input channels.", "contents": "Ascending vestibular projections: further results at cortical and thalamic levels in the cat. The purpose of this work was to precisely delineate the vestibular projection area in the cat's cortex and to trace electrophysiologically its afferent pathways at thalamic and mesencephalic levels. On anaesthetized animals, macropotentials evoked by electrical stimulation of the ampullar nerve from the horizontal semi-circular canal were recorded at three levels: on the cortex, the vestibular zone is restricted to the lower lip of the suprasylvian gyrus; in the thalamus, our results demonstrate the vestibular character of the magnocellular part of the medial geniculate body; at the mesencephalic level, our recordings indicate the existence of an ascending vestibular pathway situated laterally and ventrally with respect to the medial longitudinal bundle. The discussion focuses on two main points: 1. the precise cortical projection area of the horizontal ampullar nerve in relation to cytoarchitectonic areas and its possible functional role in motor programming. 2. the thalamic relays of the vestibulo-cortical pathway with regard to the hypothesis of two parallel input channels."}
{"id": "PMID:199452", "title": "Changes of interhemispheric hippocampal responses during conditioning in the awake rat.", "content": "The responses of the hippocampus of the awake rat to stimulation of one of its afferent pathways were measured during classical conditioning. It was found that when the contralateral hippocampus is stimulated concurrently with the presentation of a conditioned stimulus preceding either food or an aversive shock, a late (30-40 msec) negative component in the averaged evoked response can be recorded. This late component was absent when the interhemispheric stimulation was applied prior to presentation of a conditioned stimulus or when the rat was satiated or pretreated with drugs which interfere with noradrenergic or serotonergic neurotransmission. It is suggested that classical conditioning changes neurotransmission in certain  pathways in the brain and that the monoamines are involved in mediation of this change.", "contents": "Changes of interhemispheric hippocampal responses during conditioning in the awake rat. The responses of the hippocampus of the awake rat to stimulation of one of its afferent pathways were measured during classical conditioning. It was found that when the contralateral hippocampus is stimulated concurrently with the presentation of a conditioned stimulus preceding either food or an aversive shock, a late (30-40 msec) negative component in the averaged evoked response can be recorded. This late component was absent when the interhemispheric stimulation was applied prior to presentation of a conditioned stimulus or when the rat was satiated or pretreated with drugs which interfere with noradrenergic or serotonergic neurotransmission. It is suggested that classical conditioning changes neurotransmission in certain  pathways in the brain and that the monoamines are involved in mediation of this change."}
{"id": "PMID:199453", "title": "The action of a single toxic dose of 2-acetylaminofluorene or allylic alcohol on the adrenals. II. Effect on adrenal cyclic 3',5'-adenosine monophosphate concentration during the 1st and 2nd day.", "content": "In the adrenals of male Sprague-Dawley rats the concentration of cyclic 3',5'-adenosine monophosphate (cAMP) was studied 5, 10, 14, 24, 30 and 39 hours after single intoxication by 2-acetylaminofluorene (AAF) or allylic alcohol (ALL). Beside diurnal changes a transient elevation of adrenal cAMP concentration occurred when compared with the controls 10 hours after intoxication. Thereafter, up to the 30th hour of investigation the values of the experimental groups as well as those of the control groups were within the same range. In the final stage of the experiment (30-39 hours after application) ALL intoxication was associated with a significant increase in adrenal cAMP concentration whereas it was reduced to subnormal level following AAF intoxication. In an earlier experimental study (Danz et al. 1976) we found inverse behaviour of the proliferative activity in the adrenal cortex: cell division was intensified by AAF whereas ALL was ineffective. These results indicate that division growth and functional activities are alternating conditions also in the adrenals. The possible causes of the different effects of intoxication by carcinogens or by noncarcinogenic substances are discussed.", "contents": "The action of a single toxic dose of 2-acetylaminofluorene or allylic alcohol on the adrenals. II. Effect on adrenal cyclic 3',5'-adenosine monophosphate concentration during the 1st and 2nd day. In the adrenals of male Sprague-Dawley rats the concentration of cyclic 3',5'-adenosine monophosphate (cAMP) was studied 5, 10, 14, 24, 30 and 39 hours after single intoxication by 2-acetylaminofluorene (AAF) or allylic alcohol (ALL). Beside diurnal changes a transient elevation of adrenal cAMP concentration occurred when compared with the controls 10 hours after intoxication. Thereafter, up to the 30th hour of investigation the values of the experimental groups as well as those of the control groups were within the same range. In the final stage of the experiment (30-39 hours after application) ALL intoxication was associated with a significant increase in adrenal cAMP concentration whereas it was reduced to subnormal level following AAF intoxication. In an earlier experimental study (Danz et al. 1976) we found inverse behaviour of the proliferative activity in the adrenal cortex: cell division was intensified by AAF whereas ALL was ineffective. These results indicate that division growth and functional activities are alternating conditions also in the adrenals. The possible causes of the different effects of intoxication by carcinogens or by noncarcinogenic substances are discussed."}
{"id": "PMID:199465", "title": "Adrenoceptor sensitivity in disease as assessed through response to temperature alteration.", "content": "Drug receptors are usually defined in terms of specific agonists and blocking agents. The adrenoreceptor occurs in two forms, alpha and beta. From a pharmacologic point of view, this receptor concept has proved useful by allowing the development of new, selective agonists and blocking agents. From a physiologic viewpoint, there is no need for two receptors. Clinically, it is important to find out whether the pharmacologic adrenoceptors are immutable. Evidence is accumulating, both pro and con, regarding this point. Some of the effects of temperature on the response of the isolated dilator muscle of the rabbit iris to catecholamines are described. The following questions are asked: Is it not possible that there is only one adrenoceptor whose specific agonists are epinephrine or norepinephrine? Do the alpha and beta configuration depend only on the local environment? While no answers are given, it is concluded that these are clinically relavant questions.", "contents": "Adrenoceptor sensitivity in disease as assessed through response to temperature alteration. Drug receptors are usually defined in terms of specific agonists and blocking agents. The adrenoreceptor occurs in two forms, alpha and beta. From a pharmacologic point of view, this receptor concept has proved useful by allowing the development of new, selective agonists and blocking agents. From a physiologic viewpoint, there is no need for two receptors. Clinically, it is important to find out whether the pharmacologic adrenoceptors are immutable. Evidence is accumulating, both pro and con, regarding this point. Some of the effects of temperature on the response of the isolated dilator muscle of the rabbit iris to catecholamines are described. The following questions are asked: Is it not possible that there is only one adrenoceptor whose specific agonists are epinephrine or norepinephrine? Do the alpha and beta configuration depend only on the local environment? While no answers are given, it is concluded that these are clinically relavant questions."}
{"id": "PMID:199467", "title": "Cardiac adrenoceptors at low temperature: what is the experimental evidence for the adrenoceptor interconversion hypothesis?", "content": "Isolated heart preparations of frog and rat were used to test the validity of the adrenoceptor interconversion hypothesis. This hypothesis claims that low temperature converts the inotropic beta-adrenoceptors in isolated frog and rat heart to alpha-adrenoceptors. The present results do not support the adrenoceptor interconversion hypothesis. In the isolated frog ventricle, lowering the temperature from 24 C to 14 C did not significantly alter the inotropic potency of the sympathomimetic drugs isoprenaline, epinephrine, and phenylephrine and did not reduce the potency of the beta-adrenoceptor blocking drug propranolol as an epinephrine antagonist. In the isolated rat left atrium, lowering the temperature from 31 C to 17-19 C did not significantly change the inotropic potency of isoprenaline, norepinephrine and phenylephrine, did not diminish the potency of propranolol, and did not increase the potency of the alpha-adrenoceptor blocking drug phentolamine.--Benfey, B. G. Cardiac adrenoceptors at low temperature; what is the experimental evidence for the adrenoceptor interconversion hypothesis?", "contents": "Cardiac adrenoceptors at low temperature: what is the experimental evidence for the adrenoceptor interconversion hypothesis? Isolated heart preparations of frog and rat were used to test the validity of the adrenoceptor interconversion hypothesis. This hypothesis claims that low temperature converts the inotropic beta-adrenoceptors in isolated frog and rat heart to alpha-adrenoceptors. The present results do not support the adrenoceptor interconversion hypothesis. In the isolated frog ventricle, lowering the temperature from 24 C to 14 C did not significantly alter the inotropic potency of the sympathomimetic drugs isoprenaline, epinephrine, and phenylephrine and did not reduce the potency of the beta-adrenoceptor blocking drug propranolol as an epinephrine antagonist. In the isolated rat left atrium, lowering the temperature from 31 C to 17-19 C did not significantly change the inotropic potency of isoprenaline, norepinephrine and phenylephrine, did not diminish the potency of propranolol, and did not increase the potency of the alpha-adrenoceptor blocking drug phentolamine.--Benfey, B. G. Cardiac adrenoceptors at low temperature; what is the experimental evidence for the adrenoceptor interconversion hypothesis?"}
{"id": "PMID:199472", "title": "[Character of metabolism and regulating role of cholinoreactive tissue systems during hypercapnia, hypoxia and cooling].", "content": "The content of the free fatty acids, ketone bodies, total glycogen, glucose, adrenaline and noradrenaline and morpho-histochemical picture of the tissues of neuro-endocrinal system (hypophysis and adrenal) in the brain, heart, liver, skeletal muscles and blood of the white non-linear rats, were studied 2-3 min adaptation to complex atmosphere changes: gradual increase of the CO2, decrease of the O2, and cooling (in the condition of deep hypothermia the rectal temperature was--RT--19.1 +/- 0.1 degrees C). The same parameters were studied in 48 hrs after the same training (at normothermia) and in 2-3 min. after the same repeated training in 48 hrs after the first one, at RT--20.2 +/- 0.1 degrees C. The fluctuating character of the metabolism and of the regulating systems was shown.", "contents": "[Character of metabolism and regulating role of cholinoreactive tissue systems during hypercapnia, hypoxia and cooling]. The content of the free fatty acids, ketone bodies, total glycogen, glucose, adrenaline and noradrenaline and morpho-histochemical picture of the tissues of neuro-endocrinal system (hypophysis and adrenal) in the brain, heart, liver, skeletal muscles and blood of the white non-linear rats, were studied 2-3 min adaptation to complex atmosphere changes: gradual increase of the CO2, decrease of the O2, and cooling (in the condition of deep hypothermia the rectal temperature was--RT--19.1 +/- 0.1 degrees C). The same parameters were studied in 48 hrs after the same training (at normothermia) and in 2-3 min. after the same repeated training in 48 hrs after the first one, at RT--20.2 +/- 0.1 degrees C. The fluctuating character of the metabolism and of the regulating systems was shown."}
{"id": "PMID:199473", "title": "[Acceleration of the initial stages of thrombin clearance in the bloodstream of rats during stress].", "content": "In a stress due to 30-min immobilization, the initial stages of the thrombin clearance in the blood flow of rats are considerably accelerated. Thus, in 5 min after i.v. administration of thrombin I131, The blood relative radioactivity in experimental rats decreases by about 40% while in the control animals--by 20%. The same stress against the background of exogenous ACTH leads to a still greater acceleration of the thrombin clearance and the blood relative radioactivity within the 5 min decreases by 55%. The accelerated clearance of the thrombin I131 from the blood during immobilization and combination of the latter with ACTH administration is followed by its accumulation in the liver and its reduction in the lungs. The activating effect of ACTH on the thrombin I131 clearance is not, apparently, mediated through activation of the adrenal glucocorticoid function as the clearance initial stages are not accelerated after hydrocortisone administration. The clearance depends on the heparin contents in the blood: binding of endogenous heparin with protamine--sulphate leads to abolishing of the stress activating effect, and the speed of clearance in immobilized animals decreases to basal level of control animals.", "contents": "[Acceleration of the initial stages of thrombin clearance in the bloodstream of rats during stress]. In a stress due to 30-min immobilization, the initial stages of the thrombin clearance in the blood flow of rats are considerably accelerated. Thus, in 5 min after i.v. administration of thrombin I131, The blood relative radioactivity in experimental rats decreases by about 40% while in the control animals--by 20%. The same stress against the background of exogenous ACTH leads to a still greater acceleration of the thrombin clearance and the blood relative radioactivity within the 5 min decreases by 55%. The accelerated clearance of the thrombin I131 from the blood during immobilization and combination of the latter with ACTH administration is followed by its accumulation in the liver and its reduction in the lungs. The activating effect of ACTH on the thrombin I131 clearance is not, apparently, mediated through activation of the adrenal glucocorticoid function as the clearance initial stages are not accelerated after hydrocortisone administration. The clearance depends on the heparin contents in the blood: binding of endogenous heparin with protamine--sulphate leads to abolishing of the stress activating effect, and the speed of clearance in immobilized animals decreases to basal level of control animals."}
{"id": "PMID:199474", "title": "[Effect of ACTH on plasma renin activity, aldosterone level and deoxycorticosterone level in humans (author's transl)].", "content": "Plasma aldosterone level (PAL) and deoxycorticosterone level (PDL) were determined in 5 subjects of normal sodium intake and 5 subjects of low sodium intake after the intramuscular administrations of ACTH (Upjohn, Cortrosyn) 40 IU, using radioligand methods. PAL and PDL reached their peaks at one hour after the administrations of ACTH, and then decreased in their normal ranges. Pretreated with the oral administrations of Dexamethasone 2 mg/day for 2 days, these subjects had, when ACTH were injected, such a similiar pattern in PAL and PDL as the peak of one hour and the consecutive falling without the pretreating of Dexamethasone. PAL and PDL of these subjects were not different between normal sodium intake and low sodium intake during the course of the experiment.", "contents": "[Effect of ACTH on plasma renin activity, aldosterone level and deoxycorticosterone level in humans (author's transl)]. Plasma aldosterone level (PAL) and deoxycorticosterone level (PDL) were determined in 5 subjects of normal sodium intake and 5 subjects of low sodium intake after the intramuscular administrations of ACTH (Upjohn, Cortrosyn) 40 IU, using radioligand methods. PAL and PDL reached their peaks at one hour after the administrations of ACTH, and then decreased in their normal ranges. Pretreated with the oral administrations of Dexamethasone 2 mg/day for 2 days, these subjects had, when ACTH were injected, such a similiar pattern in PAL and PDL as the peak of one hour and the consecutive falling without the pretreating of Dexamethasone. PAL and PDL of these subjects were not different between normal sodium intake and low sodium intake during the course of the experiment."}
{"id": "PMID:199481", "title": "[Effect of biogenic amines on rat anterior pituitary cyclic AMP].", "content": "The effects of biogenic amines on the formation of adenosine-3',5' monophosphate (cAMP) in the anterior pituitary of rats were investigated. Pituitary halves were preincubated in a Krebs-Ringer bicarbonate buffer (pH 7.4) containing theophylline (10(-2)M) at 37 degrees C for 30 minutes and incubated in a fresh buffer for 15 minutes after the addition of test substances. Noradrenaline at 4 X 10(-4)M and serotonin at 3.3 X 10(-4)M were effective in elevating cAMP, but dopamine at 2 X 20(-4)M was ineffective. The beta adrenergic blocking agent, propranolol, effectively antagonized the cAMP response to noradrenaline, but the alpha adrenergic blocking agent, phentolamine, did not. The serotonin antagonist, methysergide, remarkably antagonized the cAMP response to serotonin, but the alpha and beta adrenergic agents did not.", "contents": "[Effect of biogenic amines on rat anterior pituitary cyclic AMP]. The effects of biogenic amines on the formation of adenosine-3',5' monophosphate (cAMP) in the anterior pituitary of rats were investigated. Pituitary halves were preincubated in a Krebs-Ringer bicarbonate buffer (pH 7.4) containing theophylline (10(-2)M) at 37 degrees C for 30 minutes and incubated in a fresh buffer for 15 minutes after the addition of test substances. Noradrenaline at 4 X 10(-4)M and serotonin at 3.3 X 10(-4)M were effective in elevating cAMP, but dopamine at 2 X 20(-4)M was ineffective. The beta adrenergic blocking agent, propranolol, effectively antagonized the cAMP response to noradrenaline, but the alpha adrenergic blocking agent, phentolamine, did not. The serotonin antagonist, methysergide, remarkably antagonized the cAMP response to serotonin, but the alpha and beta adrenergic agents did not."}
{"id": "PMID:199484", "title": "[Lipid composition of circulating lipoproteins in various types of hyperlipoproteinemia (author's transl)].", "content": "By means of simple and selective precipitation methods with polyanions, three lipoprotein fractions rich in HDL (F1), LDL (F2) and VLDL (F3) were isolated from serum of normal subjects, of normolipemic patients with atherosclerotic disease and of patients with type IIA, IIB or IV hyperlipoproteinemia. Cholesterol content was used to quantify lipoprotein fractions and to measure relative triglycerides abundance (cholesterol/triglyceride ratio and regression coefficients). Findings in the atheroscerotic patients without hyperlipoproteinemia resembled those of the controls. No correlation between cholesterol and triglycerides was obtained in F1 of the various groups. However, a significant relation was established in F2 and the relative content of triglycerides was increased progressively from type IIA, through type IIB to type IV. In all types of hyperlipoproteinemia comparable relationships were found in F3 mainly containing VLDL, the precursor of LDL. In fractions F2 and F3, types IIB and IV were clearly distinguishable from type IIA.", "contents": "[Lipid composition of circulating lipoproteins in various types of hyperlipoproteinemia (author's transl)]. By means of simple and selective precipitation methods with polyanions, three lipoprotein fractions rich in HDL (F1), LDL (F2) and VLDL (F3) were isolated from serum of normal subjects, of normolipemic patients with atherosclerotic disease and of patients with type IIA, IIB or IV hyperlipoproteinemia. Cholesterol content was used to quantify lipoprotein fractions and to measure relative triglycerides abundance (cholesterol/triglyceride ratio and regression coefficients). Findings in the atheroscerotic patients without hyperlipoproteinemia resembled those of the controls. No correlation between cholesterol and triglycerides was obtained in F1 of the various groups. However, a significant relation was established in F2 and the relative content of triglycerides was increased progressively from type IIA, through type IIB to type IV. In all types of hyperlipoproteinemia comparable relationships were found in F3 mainly containing VLDL, the precursor of LDL. In fractions F2 and F3, types IIB and IV were clearly distinguishable from type IIA."}
{"id": "PMID:199512", "title": "Polygraphic studies of kitten development: sleep state patterns.", "content": "The sequence of developmental changes in sleep pattern organization was derived from 12-hr recordings in 10-, 20 and 40-day-old kittens. Each characteristic of sleep patterning exhibited a distinct maturational sequence. Earlier changes (10-20 days) included quiet sleep (QS) increments and somatic activity decrements; later changes (20-40 days) included emergence of EEG slow waves and spindles, decrements in active sleep (AS), and diminution of QS respiratory variability. Changes in the lengths of state epochs and the types of state transitions spanned the period studied. We suggest that the differential development of the characteristics of sleep patterns reflects differential maturation of distinct nervous system elements.", "contents": "Polygraphic studies of kitten development: sleep state patterns. The sequence of developmental changes in sleep pattern organization was derived from 12-hr recordings in 10-, 20 and 40-day-old kittens. Each characteristic of sleep patterning exhibited a distinct maturational sequence. Earlier changes (10-20 days) included quiet sleep (QS) increments and somatic activity decrements; later changes (20-40 days) included emergence of EEG slow waves and spindles, decrements in active sleep (AS), and diminution of QS respiratory variability. Changes in the lengths of state epochs and the types of state transitions spanned the period studied. We suggest that the differential development of the characteristics of sleep patterns reflects differential maturation of distinct nervous system elements."}
{"id": "PMID:199515", "title": "Serum high density lipoprotein in diabetic patients.", "content": "The purpose of the present investigation was the study of HDL lipoprotein changes in patients with diabetes mellitus. The comparison was made between 40 normal and 109 diabetic subjects and the following data was obtained: relative HDL concentration (polyacrylamide gel electrophoresis), HDL-cholesterol and apolipoprotein A concentrations. We found significant decreases in HDL (18-28%) and HDL-cholesterol (31-40 mg/100 ml) in most diabetics except in those with normalized serum levels of glucose and lipids (34% and 50 mg/100 ml respectively). There was a statistically significant difference in HDL and HDL-cholesterol concentrations between patients in the latter group and other diabetic patients. There was a negative correlation between HDL and HDL-cholesterol and serum glucose levels. No statistically significant difference was found when apolipoprotein A was compared in normal and diabetic subjects. Our results suggest that a deficient binding of cholesterol to apoprotein A might be present in diabetes.", "contents": "Serum high density lipoprotein in diabetic patients. The purpose of the present investigation was the study of HDL lipoprotein changes in patients with diabetes mellitus. The comparison was made between 40 normal and 109 diabetic subjects and the following data was obtained: relative HDL concentration (polyacrylamide gel electrophoresis), HDL-cholesterol and apolipoprotein A concentrations. We found significant decreases in HDL (18-28%) and HDL-cholesterol (31-40 mg/100 ml) in most diabetics except in those with normalized serum levels of glucose and lipids (34% and 50 mg/100 ml respectively). There was a statistically significant difference in HDL and HDL-cholesterol concentrations between patients in the latter group and other diabetic patients. There was a negative correlation between HDL and HDL-cholesterol and serum glucose levels. No statistically significant difference was found when apolipoprotein A was compared in normal and diabetic subjects. Our results suggest that a deficient binding of cholesterol to apoprotein A might be present in diabetes."}
{"id": "PMID:199518", "title": "Incorporation characteristics of uracil, uridine, and orotic acid into ribonucleic acid of neoplastic cells.", "content": "Incorporation of uracil and uridine into ribonucleic acid (RNA) was compared among the ascitic and solid forms of Ehrlich mouse tumor, Morris hepatoma, Rhodamine sarcoma, gastric cancer and ulcer from human patients, and several normal rat tissues. Of these cells tested, the cells of Ehrlich ascites and solid tumors, human gastric cancer and ulcer, and certain tissues of a normal rat showed a considerably high activity. Furthermore, Ehrlich ascites tumor cells indicating a high incorporation activity was also high in activities of both phosphorylase and kinase for uridine, while Rhodamine sarcoma as a representative having a low incorporation activity was considerably low in these two enzymic activities. RNA synthesis from uridine phosphates by Rhodamine sarcoma was maintained to a fairly high extent contrary to its low activities of the phosphorylase and the kinase. Consequently, the low utilization of uracil and uridine by certain tumors was suggested to be due to the extremely low activities of both enzymes.", "contents": "Incorporation characteristics of uracil, uridine, and orotic acid into ribonucleic acid of neoplastic cells. Incorporation of uracil and uridine into ribonucleic acid (RNA) was compared among the ascitic and solid forms of Ehrlich mouse tumor, Morris hepatoma, Rhodamine sarcoma, gastric cancer and ulcer from human patients, and several normal rat tissues. Of these cells tested, the cells of Ehrlich ascites and solid tumors, human gastric cancer and ulcer, and certain tissues of a normal rat showed a considerably high activity. Furthermore, Ehrlich ascites tumor cells indicating a high incorporation activity was also high in activities of both phosphorylase and kinase for uridine, while Rhodamine sarcoma as a representative having a low incorporation activity was considerably low in these two enzymic activities. RNA synthesis from uridine phosphates by Rhodamine sarcoma was maintained to a fairly high extent contrary to its low activities of the phosphorylase and the kinase. Consequently, the low utilization of uracil and uridine by certain tumors was suggested to be due to the extremely low activities of both enzymes."}
{"id": "PMID:199520", "title": "Detection of the estrogen receptor and response to endocrine therapy in male breast cancer patients.", "content": "The estrogen receptor was measured in breast cancer of two male patients. Both patients had a positive receptor content in their tumors. The dissociation constant and number of binding sites were both very similar to those in the female counterpart. In one of the patients, the number of binding sites in the metastatic lesions of the liver was similar to that in the primary site. The patient responded well to the endocrine ablation therapy with a remission period of 8 months. The estrogen receptor was found to be positive in 12 out of 14 cases of male breast cancer reported previously including the present 2 patients. Three out of 4 cases with positive receptor contnet, including the present case, responded to orchiectomy.", "contents": "Detection of the estrogen receptor and response to endocrine therapy in male breast cancer patients. The estrogen receptor was measured in breast cancer of two male patients. Both patients had a positive receptor content in their tumors. The dissociation constant and number of binding sites were both very similar to those in the female counterpart. In one of the patients, the number of binding sites in the metastatic lesions of the liver was similar to that in the primary site. The patient responded well to the endocrine ablation therapy with a remission period of 8 months. The estrogen receptor was found to be positive in 12 out of 14 cases of male breast cancer reported previously including the present 2 patients. Three out of 4 cases with positive receptor contnet, including the present case, responded to orchiectomy."}
{"id": "PMID:199521", "title": "Stimulation of a reconstituted, microsomal NADH oxidase system by carboquone, a quinoid anticancer chemical.", "content": "Carboquone was found to greatly stimulate the aerobic NADH oxidation in the presence of both the partially purified NADH-cytochrome b5 reductase and cytochrome b5 prepared from hepatic microsomes by acting as an electron carrier from cytochrome b5 to molecular oxygen. Other quinoid anticancer chemicals, mitomycin-C, adriamycin, and daunomycin practically failed to do so.", "contents": "Stimulation of a reconstituted, microsomal NADH oxidase system by carboquone, a quinoid anticancer chemical. Carboquone was found to greatly stimulate the aerobic NADH oxidation in the presence of both the partially purified NADH-cytochrome b5 reductase and cytochrome b5 prepared from hepatic microsomes by acting as an electron carrier from cytochrome b5 to molecular oxygen. Other quinoid anticancer chemicals, mitomycin-C, adriamycin, and daunomycin practically failed to do so."}
{"id": "PMID:199523", "title": "Cytomegalovirus infection of the gastrointestinal tract in a patient with late onset immunodeficiency syndrome.", "content": "An adult with the late onset immunodeficiency syndrome developed intractable diarrhea. Widespread cytomegalovirus (CMV) infection of the gastrointestinal tract was detected antemortem with detailed morphological studies and viral culture. The CMV-type cells were especially numerous in his severely ulcerated colon. Electron microscopy of infected cells in rectal biopsy material revealed the characteristic features of CMV infection. It is likely that the CMV infection contributed to the symptom complex and the mucosal injury. Unusual opportunistic infections as a cause of diarrhea should be considered in patients with late onset immunodefociency, especially if Giardiasis is ruled out.", "contents": "Cytomegalovirus infection of the gastrointestinal tract in a patient with late onset immunodeficiency syndrome. An adult with the late onset immunodeficiency syndrome developed intractable diarrhea. Widespread cytomegalovirus (CMV) infection of the gastrointestinal tract was detected antemortem with detailed morphological studies and viral culture. The CMV-type cells were especially numerous in his severely ulcerated colon. Electron microscopy of infected cells in rectal biopsy material revealed the characteristic features of CMV infection. It is likely that the CMV infection contributed to the symptom complex and the mucosal injury. Unusual opportunistic infections as a cause of diarrhea should be considered in patients with late onset immunodefociency, especially if Giardiasis is ruled out."}
{"id": "PMID:199524", "title": "Clinical recovery owing to target parietal cell failure in a patient with Zollinger-Ellison syndrome.", "content": "A patient is presented with Zollinger-Ellison syndrome, in whom spontaneous disappearance of gastric hypersecretion and peptic ulcer disease occurred subsequent to an intercurrent illness causing acute nonspecific inflammation of the gastric mucosal lining. The dramatic clinical improvement after subsiding of the intercurrent illness was obviously linked to pronounced failure of the parietal cell mass for acid secretion and not to infarction of the gastrinoma because gastrin secretion by the tumor was unchanged.", "contents": "Clinical recovery owing to target parietal cell failure in a patient with Zollinger-Ellison syndrome. A patient is presented with Zollinger-Ellison syndrome, in whom spontaneous disappearance of gastric hypersecretion and peptic ulcer disease occurred subsequent to an intercurrent illness causing acute nonspecific inflammation of the gastric mucosal lining. The dramatic clinical improvement after subsiding of the intercurrent illness was obviously linked to pronounced failure of the parietal cell mass for acid secretion and not to infarction of the gastrinoma because gastrin secretion by the tumor was unchanged."}
{"id": "PMID:199525", "title": "Pancreatic acinar cell metabolism and function.", "content": "This review outlines progress made during the past 11 years in research related to pancreatic acinar cell metabolism and function. We have reviewed information gained at the cellular level concerning structural and functional relationships, and effects of fasting and feeding, as well as the action of gastrointestinal hormones and cholinergic agonists on acinar cells. In toto, this information outlines a significant role for gastrointestinal hormones as mediators of secretion, synthesis, and control of trophism. This information provides a basis for more sophisticated inquiries as to the mechanisms of injury of alcohol and drugs. The information may prove helpful in developing diagnostic modalities for pancreatic disease, as well as understanding the processes involved in neoplastic transformation.", "contents": "Pancreatic acinar cell metabolism and function. This review outlines progress made during the past 11 years in research related to pancreatic acinar cell metabolism and function. We have reviewed information gained at the cellular level concerning structural and functional relationships, and effects of fasting and feeding, as well as the action of gastrointestinal hormones and cholinergic agonists on acinar cells. In toto, this information outlines a significant role for gastrointestinal hormones as mediators of secretion, synthesis, and control of trophism. This information provides a basis for more sophisticated inquiries as to the mechanisms of injury of alcohol and drugs. The information may prove helpful in developing diagnostic modalities for pancreatic disease, as well as understanding the processes involved in neoplastic transformation."}
{"id": "PMID:199527", "title": "Studies of human malignant lymphomas after treatment with endoxan. I. Cytochemical studies in the respiratory enzymes succinic dehydrogenase and cytochrome oxidase.", "content": "The respiratory enzymes succinic dehydrogenase and cytochrome oxidase were studied in normal lymph node and malignant lymphoma cells under the effect of endoxan treatment. It is concluded that the decrease in the respiratory enzymes in lymphoma cells may be taken as one of the outstanding differences between the neoplastic and normal tissues.", "contents": "Studies of human malignant lymphomas after treatment with endoxan. I. Cytochemical studies in the respiratory enzymes succinic dehydrogenase and cytochrome oxidase. The respiratory enzymes succinic dehydrogenase and cytochrome oxidase were studied in normal lymph node and malignant lymphoma cells under the effect of endoxan treatment. It is concluded that the decrease in the respiratory enzymes in lymphoma cells may be taken as one of the outstanding differences between the neoplastic and normal tissues."}
{"id": "PMID:199528", "title": "Enzyme histochemistry of cultured ovarian cells. III. Histochemical characteristics of bovine granulosa and theca interna cells grown separately in cell culture.", "content": "Granulosa and theca interna cells were isolated from bovine preovulatory ovarian follicles. They were cultured separately but in the same conditions of cell culture. Both cell types, grown as monolayers, were investigated histochemically with special regard to the activity of several hydroxysteroid dehydrogenases: delta53betaOH-SDH, 17betaOH-SDH, 20alphaOH-SDH and G6P-DH. Bovine granulosa and theca interna cells during in vitro culture showed high activity of delta53betaOH-SDH and G6P-DH, the enzymes essential to progesterone biosynthesis. Enzyme pattern of cultured cells indicated continuation in vitro of luteinization, which in the normal preovulatory follicle of the bovine ovary begins prior to ovulation. There was investigated as well the influence of single doses of gonadotrophic hormones and estradiol on growth, lipid contents and enzymic activity of cultured in vitro bovine granulosa and theca interna cells.", "contents": "Enzyme histochemistry of cultured ovarian cells. III. Histochemical characteristics of bovine granulosa and theca interna cells grown separately in cell culture. Granulosa and theca interna cells were isolated from bovine preovulatory ovarian follicles. They were cultured separately but in the same conditions of cell culture. Both cell types, grown as monolayers, were investigated histochemically with special regard to the activity of several hydroxysteroid dehydrogenases: delta53betaOH-SDH, 17betaOH-SDH, 20alphaOH-SDH and G6P-DH. Bovine granulosa and theca interna cells during in vitro culture showed high activity of delta53betaOH-SDH and G6P-DH, the enzymes essential to progesterone biosynthesis. Enzyme pattern of cultured cells indicated continuation in vitro of luteinization, which in the normal preovulatory follicle of the bovine ovary begins prior to ovulation. There was investigated as well the influence of single doses of gonadotrophic hormones and estradiol on growth, lipid contents and enzymic activity of cultured in vitro bovine granulosa and theca interna cells."}
{"id": "PMID:199529", "title": "[Modification of chromosome aberrations caused by kilham virus in rat embryo cells].", "content": "Mutagenic effect of Kilham virus on the frequency of chromosome aberrations in the cells of primary and continous rat embryo cultures and the modification effect of cadmium salt on the mutagenic potential of this virus was studied. The frequency of chromosome aberrations increased in the primary rat embryo culture after Kilham virus enfection. Rat embryo culture chronically infected with Kilham virus did not differ from control continuous cells in the frequency level of chromosome aberrations. Isertion of cadmium in the process of cultivation increased the mutagenic effect of kilham virus in the primary rat embryo culture.", "contents": "[Modification of chromosome aberrations caused by kilham virus in rat embryo cells]. Mutagenic effect of Kilham virus on the frequency of chromosome aberrations in the cells of primary and continous rat embryo cultures and the modification effect of cadmium salt on the mutagenic potential of this virus was studied. The frequency of chromosome aberrations increased in the primary rat embryo culture after Kilham virus enfection. Rat embryo culture chronically infected with Kilham virus did not differ from control continuous cells in the frequency level of chromosome aberrations. Isertion of cadmium in the process of cultivation increased the mutagenic effect of kilham virus in the primary rat embryo culture."}
{"id": "PMID:199530", "title": "Anterior interosseous nerve paralysis: report of 13 cases and review of Japanese literatures.", "content": "Fifty-six cases of anterior interosseous nerve paralysis including our thirteen cases were collected by reviewing the Japanese literature. The causes of the paralysis were similar to those in the cases reported in other countries. Paralysis is often only partial, and this is of importance in the differential diagnosis.", "contents": "Anterior interosseous nerve paralysis: report of 13 cases and review of Japanese literatures. Fifty-six cases of anterior interosseous nerve paralysis including our thirteen cases were collected by reviewing the Japanese literature. The causes of the paralysis were similar to those in the cases reported in other countries. Paralysis is often only partial, and this is of importance in the differential diagnosis."}
{"id": "PMID:199532", "title": "[Double controlled regulation of renin release by the sympathetic nervous system. Stimulation via beta receptors and inhibition via alpha receptors].", "content": "The beta-sympathomimetic amine isoprenaline increases the plasma renin concentration by a stimulation of beta-receptors which control renin release. Isoprenaline also lowers systemic blood pressure and causes a reflex-mediated activation of the sympathetic nervous system. In these investigations it has been tested to see whether the catecholamines released by this activation modulate renin release by stimulation of certain alpha-receptors. Pretreatment of rats with reserpine or with the ganglionic blocking agent Trimethidinium enhanced the increase in plasma renin concentration induced by isoprenaline. So did pretreatment with the irreversible alpha-receptor antagonist phenoxybenzamine. Renal denervation also increased the effect of isoprenaline on plasma renin concentration. It is concluded that catecholamines released from the sympathetic nervous system can decrease renin secretion by an activation of certain alpha-receptors. The sympathetic nervous system may thus exert control of renin release by beta-receptors which stimulate and by alpha-receptors which diminish renin secretion.", "contents": "[Double controlled regulation of renin release by the sympathetic nervous system. Stimulation via beta receptors and inhibition via alpha receptors]. The beta-sympathomimetic amine isoprenaline increases the plasma renin concentration by a stimulation of beta-receptors which control renin release. Isoprenaline also lowers systemic blood pressure and causes a reflex-mediated activation of the sympathetic nervous system. In these investigations it has been tested to see whether the catecholamines released by this activation modulate renin release by stimulation of certain alpha-receptors. Pretreatment of rats with reserpine or with the ganglionic blocking agent Trimethidinium enhanced the increase in plasma renin concentration induced by isoprenaline. So did pretreatment with the irreversible alpha-receptor antagonist phenoxybenzamine. Renal denervation also increased the effect of isoprenaline on plasma renin concentration. It is concluded that catecholamines released from the sympathetic nervous system can decrease renin secretion by an activation of certain alpha-receptors. The sympathetic nervous system may thus exert control of renin release by beta-receptors which stimulate and by alpha-receptors which diminish renin secretion."}
{"id": "PMID:199533", "title": "[The mechanism of action of histamine on the myocardium and the smooth vascular muscles].", "content": "Histamine-H1-receptors are only present in the left atrium of guinea-pig hearts, whereas the ventricular myocardium contains histamine-H2-receptors exclusively. Although the stimulation of both receptor types causes positive intropic effects, only the H2-receptor response is closely associated with increases of cyclic AMP. H1- as well as H2-receptors are present in the rabbit mesenteric artery. Cyclic AMP serves as a messenger for H2-receptor mediated relaxation only and not for H1-receptor mediated contraction. Thus, the different effects on the cyclic AMP-system must also be considered in H1- and H2-receptor differentiation.", "contents": "[The mechanism of action of histamine on the myocardium and the smooth vascular muscles]. Histamine-H1-receptors are only present in the left atrium of guinea-pig hearts, whereas the ventricular myocardium contains histamine-H2-receptors exclusively. Although the stimulation of both receptor types causes positive intropic effects, only the H2-receptor response is closely associated with increases of cyclic AMP. H1- as well as H2-receptors are present in the rabbit mesenteric artery. Cyclic AMP serves as a messenger for H2-receptor mediated relaxation only and not for H1-receptor mediated contraction. Thus, the different effects on the cyclic AMP-system must also be considered in H1- and H2-receptor differentiation."}
{"id": "PMID:199534", "title": "[Measurement of liver circulation by means of an ultrasonic Doppler flow measuring device].", "content": "The ultrasonic-Doppler technique is a very simple method for flow measurement. With this method the generally accepted mechanism of hepatic arterial flow increase after reduction or interruption of the portal vein flow could be confirmed. The increase was not related to cardiac output. Previous doubts about the portal vein flow behaviour after suppression of hepatic artery flow were decided, joining the little group of authors, who did not observe a variation of the portal vein flow in this condition. The concept of the autoregulation of the liver blood supply seems to be connected to the hepatic arterial system only. Although an increase of the hepatic artery flow after infusion of isoproterenol supports the existance of beta-receptors in the hepatic arterial system, it could be proved, that there was no reduction after propranolol infusion. This suggests, that autoregulation of the liver blood supply is not connected to the beta-receptors only.", "contents": "[Measurement of liver circulation by means of an ultrasonic Doppler flow measuring device]. The ultrasonic-Doppler technique is a very simple method for flow measurement. With this method the generally accepted mechanism of hepatic arterial flow increase after reduction or interruption of the portal vein flow could be confirmed. The increase was not related to cardiac output. Previous doubts about the portal vein flow behaviour after suppression of hepatic artery flow were decided, joining the little group of authors, who did not observe a variation of the portal vein flow in this condition. The concept of the autoregulation of the liver blood supply seems to be connected to the hepatic arterial system only. Although an increase of the hepatic artery flow after infusion of isoproterenol supports the existance of beta-receptors in the hepatic arterial system, it could be proved, that there was no reduction after propranolol infusion. This suggests, that autoregulation of the liver blood supply is not connected to the beta-receptors only."}
{"id": "PMID:199537", "title": "Delivering Mental Health Services to an ambulatory, low-income population. Lincoln Community Health Center, Durham, North Carolina.", "content": "The social work and mental health unit of a comprehensive neighborhood health center delivers mental health services in coordination with general health services to ambulatory patients in a predominantly low-income black community. The unit works with other general health, mental health, and social service resources to provide a broad continuum of coordinated care. Services are provided to individuals, families, and groups, along with consultation, education, training, and referral. Before the unit was established in July 1971, the patients it serves were seen only for crisis intervention and in emergency rooms and did not have the benefit of a thorough evaluation or follow-up. Staff of the unit now identify potential medical and emotional problems before they reach the crisis stage, and they maintain contact with the patients to ensure that the prescribed regimen is carried out.", "contents": "Delivering Mental Health Services to an ambulatory, low-income population. Lincoln Community Health Center, Durham, North Carolina. The social work and mental health unit of a comprehensive neighborhood health center delivers mental health services in coordination with general health services to ambulatory patients in a predominantly low-income black community. The unit works with other general health, mental health, and social service resources to provide a broad continuum of coordinated care. Services are provided to individuals, families, and groups, along with consultation, education, training, and referral. Before the unit was established in July 1971, the patients it serves were seen only for crisis intervention and in emergency rooms and did not have the benefit of a thorough evaluation or follow-up. Staff of the unit now identify potential medical and emotional problems before they reach the crisis stage, and they maintain contact with the patients to ensure that the prescribed regimen is carried out."}
{"id": "PMID:199539", "title": "[Fundamentals of anti-NADase reaction in A-streptococcus infections and its determination in microtiter test (author's transl)].", "content": "A-streptococci of known serotypes were investigated for their ability to produce NADase. For this, a microtiter-dilution technique was employed. The results were compared with those of Lazarides and Bernheimer who had determined the NADase-activity in an other way. It seems, that there is no fixed relation of NADase-production and growth curve for all of the strains. At the moment, anti-NADase can be determined only with a macrotechnique, which is, with respect to costs, time work and others, difficult to handle. A microtiter-technique is described, which is adapted to the macrotechnique. With 426 young men in the age of 18-20 years titers were found between less than 50 and 800 with a 95% level between 200 and 300. The reproducibility of the micromethod is like that of the macromethod. It is of great importance to redetermine the titer in the upper limit of normal and those which are expected to rise. The possibility to seize also infections with G- and C-streptococci is mentioned.", "contents": "[Fundamentals of anti-NADase reaction in A-streptococcus infections and its determination in microtiter test (author's transl)]. A-streptococci of known serotypes were investigated for their ability to produce NADase. For this, a microtiter-dilution technique was employed. The results were compared with those of Lazarides and Bernheimer who had determined the NADase-activity in an other way. It seems, that there is no fixed relation of NADase-production and growth curve for all of the strains. At the moment, anti-NADase can be determined only with a macrotechnique, which is, with respect to costs, time work and others, difficult to handle. A microtiter-technique is described, which is adapted to the macrotechnique. With 426 young men in the age of 18-20 years titers were found between less than 50 and 800 with a 95% level between 200 and 300. The reproducibility of the micromethod is like that of the macromethod. It is of great importance to redetermine the titer in the upper limit of normal and those which are expected to rise. The possibility to seize also infections with G- and C-streptococci is mentioned."}
{"id": "PMID:199540", "title": "[Adjuvant activity of gram-negative bacteria and their structural components (author's transl)].", "content": "Regarding the adjuvant activity of gram-negative bacteria we have to distinguish at least 4 different potencies, i.e., 1) increase in the production of circulating antibodies during the primary and secondary immune responses; 2) induction of susceptibility to systemic anaphylaxis; 3) prompt production of experimental \"allergic\" diseases, and 4) increase in resistance to infections. Although all gram-negative bacteria contain several structural components with adjuvant potencies, the immunopotentiating effectiveness of the corresponding whole bacteria becomes--with the exception of killed cells of Bordetella pertussis--only detectable to a weak degree.", "contents": "[Adjuvant activity of gram-negative bacteria and their structural components (author's transl)]. Regarding the adjuvant activity of gram-negative bacteria we have to distinguish at least 4 different potencies, i.e., 1) increase in the production of circulating antibodies during the primary and secondary immune responses; 2) induction of susceptibility to systemic anaphylaxis; 3) prompt production of experimental \"allergic\" diseases, and 4) increase in resistance to infections. Although all gram-negative bacteria contain several structural components with adjuvant potencies, the immunopotentiating effectiveness of the corresponding whole bacteria becomes--with the exception of killed cells of Bordetella pertussis--only detectable to a weak degree."}
{"id": "PMID:199543", "title": "Relationship between the Epstein-Barr virus and undifferentiated nasopharyngeal carcinoma: correlated nucleic acid hybridization and histopathological examination.", "content": "In order to examine critically the closeness of association between Epstein-Barr virus (EBV) DNA and nasopharyngeal carcinoma (NPC) a correlated histopathological and nucleic acid hybridization study was performed on 51 undifferentiated NPC, 4 NPC with some signs of squamous differentiation, 7 nasophayngeal tumors of other histological types and 14 head and neck carcinomas located outside the nasopharynx. All 51 undifferentiated NPCs contained significant numbers of EBV-genome copies per cell. Two of the somewhat differentiated NPCs were also EBV-DNA-positive, whereas 2 were negative. Of the 7 other nasopharyngeal tumors, 1 was EBV-DNA-positive. Histological examination, however, showed that this was a typical Burkitt lymphoma. The other 6 tumors were all EBV-DNA-negative lymphoproliferative malignancies. All 14 had head and neck carcinomas located outside the nasopharynx were EBV-DNA-negative. The sera of undifferentiated NPC patients had elevated antibody titers against the EBV-determined antigens, the EA (D) componet in particular. These findings confirm that there is a regular association between EBV-DNA and undifferentiated NPC.", "contents": "Relationship between the Epstein-Barr virus and undifferentiated nasopharyngeal carcinoma: correlated nucleic acid hybridization and histopathological examination. In order to examine critically the closeness of association between Epstein-Barr virus (EBV) DNA and nasopharyngeal carcinoma (NPC) a correlated histopathological and nucleic acid hybridization study was performed on 51 undifferentiated NPC, 4 NPC with some signs of squamous differentiation, 7 nasophayngeal tumors of other histological types and 14 head and neck carcinomas located outside the nasopharynx. All 51 undifferentiated NPCs contained significant numbers of EBV-genome copies per cell. Two of the somewhat differentiated NPCs were also EBV-DNA-positive, whereas 2 were negative. Of the 7 other nasopharyngeal tumors, 1 was EBV-DNA-positive. Histological examination, however, showed that this was a typical Burkitt lymphoma. The other 6 tumors were all EBV-DNA-negative lymphoproliferative malignancies. All 14 had head and neck carcinomas located outside the nasopharynx were EBV-DNA-negative. The sera of undifferentiated NPC patients had elevated antibody titers against the EBV-determined antigens, the EA (D) componet in particular. These findings confirm that there is a regular association between EBV-DNA and undifferentiated NPC."}
{"id": "PMID:199544", "title": "Cell mediated immunity during infectious mononucleosis to Epstein-Barr virus associated antigens.", "content": "Twenty-three patients with recent infectious mononucleosis were studied for cell-mediated immunity to Epstein-Barr virus (EBV)-associated antigens. By means of a virion-containing antigen preparation, (P3J), leukocyte migration inhibition was demonstrated in 6 of 13 patients with acute infectious mononucleosis (IM) and in 6 of 10 patients studied during the convalescent period. Inhibition with a soluble antigen (S) preparation was seen in only a few patients at all stages of the illness. Lymphocyte blast transformation on exposure to P3J occurred in 4 of 9 patients with acute IM; no other study group reacted. Control donors lacking anti-EBV antibodies did not demonstrate migration inhibition or blast transformation with either P3J or S. Control donors with evidence of previous EBV infection did demonstrate migration inhibition with P3J (8 of 12) and S (3 of 10). These studies indicated that cell-mediate immunity to EBV-associated antigens could be detected by either leukocyte migration inhibition or lymphocyte blast transformation, but neither assay is diagnostic of infectious mononucleosis.", "contents": "Cell mediated immunity during infectious mononucleosis to Epstein-Barr virus associated antigens. Twenty-three patients with recent infectious mononucleosis were studied for cell-mediated immunity to Epstein-Barr virus (EBV)-associated antigens. By means of a virion-containing antigen preparation, (P3J), leukocyte migration inhibition was demonstrated in 6 of 13 patients with acute infectious mononucleosis (IM) and in 6 of 10 patients studied during the convalescent period. Inhibition with a soluble antigen (S) preparation was seen in only a few patients at all stages of the illness. Lymphocyte blast transformation on exposure to P3J occurred in 4 of 9 patients with acute IM; no other study group reacted. Control donors lacking anti-EBV antibodies did not demonstrate migration inhibition or blast transformation with either P3J or S. Control donors with evidence of previous EBV infection did demonstrate migration inhibition with P3J (8 of 12) and S (3 of 10). These studies indicated that cell-mediate immunity to EBV-associated antigens could be detected by either leukocyte migration inhibition or lymphocyte blast transformation, but neither assay is diagnostic of infectious mononucleosis."}
{"id": "PMID:199545", "title": "Production of hybrid cells by fusion of human malignant tumour cells and primary mouse embryo cells.", "content": "Hybrid cells with a subtetraploid mouse chromosome complement were produced by fusion of three types of human tumour cells with primary mouse embryo cells. The most frequently present presumptive human chromosome was 21. Numerous chromosome rearrangements were present. Some hybrid cells produced regressing tumours in mice.", "contents": "Production of hybrid cells by fusion of human malignant tumour cells and primary mouse embryo cells. Hybrid cells with a subtetraploid mouse chromosome complement were produced by fusion of three types of human tumour cells with primary mouse embryo cells. The most frequently present presumptive human chromosome was 21. Numerous chromosome rearrangements were present. Some hybrid cells produced regressing tumours in mice."}
{"id": "PMID:199546", "title": "Bovine leukemia virus specific antibodies among French cattle. II. Radioimmunoassay with the major structural protein (BLV p24).", "content": "A radioimmunoassay (RIA) for the major internal protein of the bovine leukemia virus (BLV p24) was established using anti-BLV p24 natural antibodies and purified 125I-labelled BLV p24. The final precipitation of the immune complexes was realized by a preparation of inactivated Staphylococcus aureau Cowan I. Sera from 363 cows belonging to (1) leukemic herds, (2) non-leukemic but BLV-exposed herds, and (3) apparently unexposed herds were studied comparatively in BLV p24 RIA, complement fixation and immunodiffusion. The BLV p24 RIA appeared much more senstive than the two other methods in the detection of positive sera. With this method 100% of the leukemic animals, excluding those with juvenile lymphosarcoma, presented very high antibody titers (greater than or equal to 10,000). Practically all cows with persistent lymphocytosis were also positive with slightly lower levels of antibodies, confirming the relationship between BLV infection and the persistent lymphycytosis. Moreover, about two-thirds of the hematologically suspect animals and one-third of the normal animals from BLV-exposed herds were found positive, whereas 100% of the sera from unexposed cows remained negative for anti-BLV p24 antibodies.", "contents": "Bovine leukemia virus specific antibodies among French cattle. II. Radioimmunoassay with the major structural protein (BLV p24). A radioimmunoassay (RIA) for the major internal protein of the bovine leukemia virus (BLV p24) was established using anti-BLV p24 natural antibodies and purified 125I-labelled BLV p24. The final precipitation of the immune complexes was realized by a preparation of inactivated Staphylococcus aureau Cowan I. Sera from 363 cows belonging to (1) leukemic herds, (2) non-leukemic but BLV-exposed herds, and (3) apparently unexposed herds were studied comparatively in BLV p24 RIA, complement fixation and immunodiffusion. The BLV p24 RIA appeared much more senstive than the two other methods in the detection of positive sera. With this method 100% of the leukemic animals, excluding those with juvenile lymphosarcoma, presented very high antibody titers (greater than or equal to 10,000). Practically all cows with persistent lymphocytosis were also positive with slightly lower levels of antibodies, confirming the relationship between BLV infection and the persistent lymphycytosis. Moreover, about two-thirds of the hematologically suspect animals and one-third of the normal animals from BLV-exposed herds were found positive, whereas 100% of the sera from unexposed cows remained negative for anti-BLV p24 antibodies."}
{"id": "PMID:199547", "title": "Adenylate cyclase activity and the cAMP level are not directly correlated with transformation by avian sarcoma viruses.", "content": "The adenylate cyclase activity was measured in chick embryo fibroblasts (CEF) infected with temperature-sensitive mutants (ts) of avian sarcoma virus (ASV). When CEF transformed with a (ts) mutant at 36 degrees C were incubated at the non-permissive temperature (41 degrees C), recovery from the low adenylate cyclase activity detectable in the transformed state was slower than the disappearance of signs of morphological transformation. After a downward shift of the temperature the activity decreased and this change was also slower than the alteration of cell morphology. The affinity of the enzyme system for ATP also changed after, and not during, morphological alteration. No significant difference was observed between the cAMP levels in ASV-transformed and non-infected CEF. These findings are consistent with the idea that adenylate cyclase is not involved in cell transformation and that the change in its activity is secondary to cell transformation.", "contents": "Adenylate cyclase activity and the cAMP level are not directly correlated with transformation by avian sarcoma viruses. The adenylate cyclase activity was measured in chick embryo fibroblasts (CEF) infected with temperature-sensitive mutants (ts) of avian sarcoma virus (ASV). When CEF transformed with a (ts) mutant at 36 degrees C were incubated at the non-permissive temperature (41 degrees C), recovery from the low adenylate cyclase activity detectable in the transformed state was slower than the disappearance of signs of morphological transformation. After a downward shift of the temperature the activity decreased and this change was also slower than the alteration of cell morphology. The affinity of the enzyme system for ATP also changed after, and not during, morphological alteration. No significant difference was observed between the cAMP levels in ASV-transformed and non-infected CEF. These findings are consistent with the idea that adenylate cyclase is not involved in cell transformation and that the change in its activity is secondary to cell transformation."}
{"id": "PMID:199548", "title": "Development of a congeneic line of the GR mouse strain without early mammary tumours.", "content": "Based on the previous observation that Mtv-2 controls the appearance of pregnancy-dependent mammary tumours and the early expression of mammary tumour virus (MTV)-antigens in the milk, an attempt was made to develop a congeneic GR line, without this locus, by introducing genetic material of the C57BL/10 strain. The cross-intercross system was used for this purpose. The mice of the even-numbered generations were selected for the absence of the Mtv-2 locus with the early maammary tumour (EMT) test and during the later cycles with the immunodiffusion (ID) test for MTV-antigens in the milk. After six cycles of cross-intercross, brother-sister mating was started with mice selected for the absence of Mtv-2. After two brother-sister matings the milk-transmitted MTV was eliminated by foster-nursing. Of the foster-nursed subline 233 mice (16 of the first, 118 of the second and 99 of the third generation) were tested for the presence of Mtv-2 with one or two of the following three methods: (1) ID-test, (2) EMT-test and (3) by examination of the development of spontaneous mammary tumours in breeding females. The tests were negative in 226 mice. This indicates that Mtv-2 was absent in nearly all mice of the congeneic subline. The positive reactions in the seven other tested mice were weaker than that observed in the GR strain and in GR mice foster-nursed by BALB/c. The presence of the Mtv-2 gene in the seven positive mice of the congeneic line is doubtful. With the ID test, viral antigens were detectable in 50% of the milk samples from the first lactation period of mice of the segregating backcross I population [GR congeneic X (GR congeneic X GR)], indicating a one-gene difference between the congeneic GR line and the progenitor GR strain.", "contents": "Development of a congeneic line of the GR mouse strain without early mammary tumours. Based on the previous observation that Mtv-2 controls the appearance of pregnancy-dependent mammary tumours and the early expression of mammary tumour virus (MTV)-antigens in the milk, an attempt was made to develop a congeneic GR line, without this locus, by introducing genetic material of the C57BL/10 strain. The cross-intercross system was used for this purpose. The mice of the even-numbered generations were selected for the absence of the Mtv-2 locus with the early maammary tumour (EMT) test and during the later cycles with the immunodiffusion (ID) test for MTV-antigens in the milk. After six cycles of cross-intercross, brother-sister mating was started with mice selected for the absence of Mtv-2. After two brother-sister matings the milk-transmitted MTV was eliminated by foster-nursing. Of the foster-nursed subline 233 mice (16 of the first, 118 of the second and 99 of the third generation) were tested for the presence of Mtv-2 with one or two of the following three methods: (1) ID-test, (2) EMT-test and (3) by examination of the development of spontaneous mammary tumours in breeding females. The tests were negative in 226 mice. This indicates that Mtv-2 was absent in nearly all mice of the congeneic subline. The positive reactions in the seven other tested mice were weaker than that observed in the GR strain and in GR mice foster-nursed by BALB/c. The presence of the Mtv-2 gene in the seven positive mice of the congeneic line is doubtful. With the ID test, viral antigens were detectable in 50% of the milk samples from the first lactation period of mice of the segregating backcross I population [GR congeneic X (GR congeneic X GR)], indicating a one-gene difference between the congeneic GR line and the progenitor GR strain."}
{"id": "PMID:199549", "title": "Resistance of guinea-pig hepatoma cells to complement-mediated lysis induced by ascites fluid or serum from tumor-bearing animals.", "content": "The mechanisms of tumor cell susceptibility and resistance to cytotoxic antibodies were investigated in the guinea-pig ascites hepatoma (line-1 and line-10) system. Treatment of line-specific rabbit antibody-coated tumor cells by ascitic fluid, by serum of tumor bearers or by tumor extract inhibited subsequent complement-mediated lysis. Inhibition by ascitic fluid and serum was not line-specific, but inhibition by tumor extract was line-specific. Treatment of tumor cells with ascitic fluid or tumor extract prior to exposure to specific cytotoxic antibody and complement did not inhibit lysis. Incubation of cytotoxic rabbit antisera with ascitic fluid, tumor-bearer serum or tumor extract neutralized their complement-dependent cytotoxic activity on tumor cells. Tumor-immune guinea-pigs exhibited line-specific delayed cutaneous reactions after injection with ascitic fluid or tumor extract. Studies with indrect immunofluorescence revealed that exposure to ascites fluid or tumor extract caused a rapid shedding of rabbit antibodies from the tumor cell surface. Evidence is presented indicating that the active fraction of ascites fluid was associated with immune complexes consisting of IgG and tumor antigen in excess. The relevance of these findings to tumor escape from immune destruction in vivo is discussed.", "contents": "Resistance of guinea-pig hepatoma cells to complement-mediated lysis induced by ascites fluid or serum from tumor-bearing animals. The mechanisms of tumor cell susceptibility and resistance to cytotoxic antibodies were investigated in the guinea-pig ascites hepatoma (line-1 and line-10) system. Treatment of line-specific rabbit antibody-coated tumor cells by ascitic fluid, by serum of tumor bearers or by tumor extract inhibited subsequent complement-mediated lysis. Inhibition by ascitic fluid and serum was not line-specific, but inhibition by tumor extract was line-specific. Treatment of tumor cells with ascitic fluid or tumor extract prior to exposure to specific cytotoxic antibody and complement did not inhibit lysis. Incubation of cytotoxic rabbit antisera with ascitic fluid, tumor-bearer serum or tumor extract neutralized their complement-dependent cytotoxic activity on tumor cells. Tumor-immune guinea-pigs exhibited line-specific delayed cutaneous reactions after injection with ascitic fluid or tumor extract. Studies with indrect immunofluorescence revealed that exposure to ascites fluid or tumor extract caused a rapid shedding of rabbit antibodies from the tumor cell surface. Evidence is presented indicating that the active fraction of ascites fluid was associated with immune complexes consisting of IgG and tumor antigen in excess. The relevance of these findings to tumor escape from immune destruction in vivo is discussed."}
{"id": "PMID:199550", "title": "In vivo and in vitro TSTA-inducing activity of temperature-sensitive (ts) mutants of SV40.", "content": "In vivo TSTA induction in Syrian hamsters was studied with the use of SV40 ts mutants (A, B, C, BC and D). The ts A30, TS A239 and possibly also the ts BC210 mutants were defective in resistance-inducing activity in hamsters in contrast to wild type SV40 and other ts mutnats. At the permissive temperature ts A30 and ts A239 did not induce TSTA in hamster cells during abortive infection in vitro, while they did so in green monkey cells at both permissive and non-permissive temperatures. In hamster cells transformed by ts A30, ts A239 and ts A209 mutants none at all or very little TSTA was detected by in vivo transplantation immunological tests. Thus, expression of TSTA induced by these three SV40 ts A mutants was found to be dependent from the species of infected cells and was being a temperature independent viral function.", "contents": "In vivo and in vitro TSTA-inducing activity of temperature-sensitive (ts) mutants of SV40. In vivo TSTA induction in Syrian hamsters was studied with the use of SV40 ts mutants (A, B, C, BC and D). The ts A30, TS A239 and possibly also the ts BC210 mutants were defective in resistance-inducing activity in hamsters in contrast to wild type SV40 and other ts mutnats. At the permissive temperature ts A30 and ts A239 did not induce TSTA in hamster cells during abortive infection in vitro, while they did so in green monkey cells at both permissive and non-permissive temperatures. In hamster cells transformed by ts A30, ts A239 and ts A209 mutants none at all or very little TSTA was detected by in vivo transplantation immunological tests. Thus, expression of TSTA induced by these three SV40 ts A mutants was found to be dependent from the species of infected cells and was being a temperature independent viral function."}
{"id": "PMID:199555", "title": "The electrophysiological effects of lithium in the rat.", "content": "The effects of lithium on the tail nerve conduction velocity of the rat were studied. No effect of lithium on the conduction velocity was found, even at toxic serum lithium levels. No effect of lithium on repetitive stimulation of the distal forelimb flexor muscles was seen. The results suggest that electrophysiological measurements do not provide an effective means of titrating serum lithium levels in the rat. The results may have clinical signficance since they provide evidence against neuropathic or neuromuscular transmission defects as the cause of the transient weakness of some patients taking lithium.", "contents": "The electrophysiological effects of lithium in the rat. The effects of lithium on the tail nerve conduction velocity of the rat were studied. No effect of lithium on the conduction velocity was found, even at toxic serum lithium levels. No effect of lithium on repetitive stimulation of the distal forelimb flexor muscles was seen. The results suggest that electrophysiological measurements do not provide an effective means of titrating serum lithium levels in the rat. The results may have clinical signficance since they provide evidence against neuropathic or neuromuscular transmission defects as the cause of the transient weakness of some patients taking lithium."}
{"id": "PMID:199556", "title": "Increased intraocular pressure following topical azide or nitroprusside.", "content": "In rabbits the topical administration of sodium azide (NaNs) or sodium nitroprusside (SNP) increased intraocular pressure in a dose-response manner. These agents, which activate guanylate cyclase, elevated cyclic GMP in the aqueous humor. Systemic blood pressure and pulse were not altered. Tonographic outflow facility was unchanged, suggesting an increase in aqueous humor flow as the mechanism for the elevation of intraocular pressure. Posterior chamber aqueous humor ascorbate concentration was decreased in the eye receiving the NaN3 or SNP. Systemic pretreatment with phenoxybenzamine, an alpha-adrenergic blocking agent, prevented the elevation of intraocular pressure observed following NaN3 and SNP. Pretreatment with systemic indomethacin, propranolol, or acetazolamide or the topical application of atropine or epinephrine failed to alter the elevation of intraocular pressure by either NaN3 or SNP.", "contents": "Increased intraocular pressure following topical azide or nitroprusside. In rabbits the topical administration of sodium azide (NaNs) or sodium nitroprusside (SNP) increased intraocular pressure in a dose-response manner. These agents, which activate guanylate cyclase, elevated cyclic GMP in the aqueous humor. Systemic blood pressure and pulse were not altered. Tonographic outflow facility was unchanged, suggesting an increase in aqueous humor flow as the mechanism for the elevation of intraocular pressure. Posterior chamber aqueous humor ascorbate concentration was decreased in the eye receiving the NaN3 or SNP. Systemic pretreatment with phenoxybenzamine, an alpha-adrenergic blocking agent, prevented the elevation of intraocular pressure observed following NaN3 and SNP. Pretreatment with systemic indomethacin, propranolol, or acetazolamide or the topical application of atropine or epinephrine failed to alter the elevation of intraocular pressure by either NaN3 or SNP."}
{"id": "PMID:199557", "title": "[Vesicular fluid of hereditary bullous dystrophic epidermolysis splits alpha 1-antitrypsin].", "content": "In epidermolysis hereditaria bullosa dystrophica increased collagenase activity can be detected and seems to be one of the pathogenetic mechanisms of this disease. Neither the origin nor the mechanism of increased collagenolysis is known. Whether the cause of the enzymatic imbalance is the increased collagenase production or decreased collagenase-inhibitor activity cannot be decided. Factors of decreased protease inhibitor activity could be the quantitative or qualitative defect or the inactivation of the inhibitor. Clear, sterile vesicular fluid was incubated with alpha-1-antitrypsin, which is known to inhibit collagenase. By means of an immunoelectrophoretic method the cleaving of the inhibitor into two antigenic split products was found. We suggest that this might be responsible for the increased collagenolysis in this form of epidermolysis.", "contents": "[Vesicular fluid of hereditary bullous dystrophic epidermolysis splits alpha 1-antitrypsin]. In epidermolysis hereditaria bullosa dystrophica increased collagenase activity can be detected and seems to be one of the pathogenetic mechanisms of this disease. Neither the origin nor the mechanism of increased collagenolysis is known. Whether the cause of the enzymatic imbalance is the increased collagenase production or decreased collagenase-inhibitor activity cannot be decided. Factors of decreased protease inhibitor activity could be the quantitative or qualitative defect or the inactivation of the inhibitor. Clear, sterile vesicular fluid was incubated with alpha-1-antitrypsin, which is known to inhibit collagenase. By means of an immunoelectrophoretic method the cleaving of the inhibitor into two antigenic split products was found. We suggest that this might be responsible for the increased collagenolysis in this form of epidermolysis."}
{"id": "PMID:199558", "title": "A study of Cytomegalovirus, Epstein-Barr virus and Herpesvirus hominis (types 1 and 2) antibody in institutionalized and non-institutionalized children.", "content": "In an attempt to demonstrate differences in antibody prevalence between free-living and institutionalized children, antibodies to Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Herpesvirus hominis (HVH), types 1 and 2, were assayed in 123 children. The children comprised three groups consisting of 41 institutionalized patients with Down's syndrome (all non-disjunctive trisomy-G karyotype and equal numbers of age-, sex-, and race-matched non-mongoloid institutionalized subjects and non-institutionalized normal controls. CMV antibody titer values were statistically similar in the three groups. However, fewer mongoloids (21.9%) were seropositive than other institutionalized retardates (39.0%) and normal control subjects (43.9%). Antibody titer values to EBV were also similar; however, in comparison to the other groups, significantly more mongoloids were seropositive at younger ages. More mongoloids were seropositive to HVH-1 and had higher antibody titers than the other two groups. Antibody to HVH-2 was more prevalent in institutionalized subjects, 85.4% in mongoloids and 65.8% in other institutionalized retardates, than in normal non-institutionalized children (26.8%).", "contents": "A study of Cytomegalovirus, Epstein-Barr virus and Herpesvirus hominis (types 1 and 2) antibody in institutionalized and non-institutionalized children. In an attempt to demonstrate differences in antibody prevalence between free-living and institutionalized children, antibodies to Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Herpesvirus hominis (HVH), types 1 and 2, were assayed in 123 children. The children comprised three groups consisting of 41 institutionalized patients with Down's syndrome (all non-disjunctive trisomy-G karyotype and equal numbers of age-, sex-, and race-matched non-mongoloid institutionalized subjects and non-institutionalized normal controls. CMV antibody titer values were statistically similar in the three groups. However, fewer mongoloids (21.9%) were seropositive than other institutionalized retardates (39.0%) and normal control subjects (43.9%). Antibody titer values to EBV were also similar; however, in comparison to the other groups, significantly more mongoloids were seropositive at younger ages. More mongoloids were seropositive to HVH-1 and had higher antibody titers than the other two groups. Antibody to HVH-2 was more prevalent in institutionalized subjects, 85.4% in mongoloids and 65.8% in other institutionalized retardates, than in normal non-institutionalized children (26.8%)."}
{"id": "PMID:199560", "title": "Biochemical analysis of genetic recombination in eukaryotes.", "content": "Recent studies concerning molecular mechanisms of genetic recombination in eukaryotes are reviewed. Since many of these studies have focused on the testable predictions arising from the hybrid DNA theory of genetic recombination, this theory is summarised. Experiments to determine the time of meiotic crossing-over and the structure of the synaptonemal complex which facilitates meiotic crossing-over are described. Investigations of DNA nicking and repair events implicated in recombination are discussed. Properties of proteins which may facilitate hybrid DNA formation, and biochemical evidence for hybrid DNA formation are presented. Finally, a nuclease which has been implicated in gene conversion is described.", "contents": "Biochemical analysis of genetic recombination in eukaryotes. Recent studies concerning molecular mechanisms of genetic recombination in eukaryotes are reviewed. Since many of these studies have focused on the testable predictions arising from the hybrid DNA theory of genetic recombination, this theory is summarised. Experiments to determine the time of meiotic crossing-over and the structure of the synaptonemal complex which facilitates meiotic crossing-over are described. Investigations of DNA nicking and repair events implicated in recombination are discussed. Properties of proteins which may facilitate hybrid DNA formation, and biochemical evidence for hybrid DNA formation are presented. Finally, a nuclease which has been implicated in gene conversion is described."}
{"id": "PMID:199561", "title": "A simple technique for supporting single cells in electron microscopic immunocytochemistry and embedding.", "content": "Cell suspensions of rat anterior pituitaries were filtered with a polycarbonate filter (pore size 3 micron) and fixed on the filter. After fixation the cells were adherent to the filter and immunocytochemical staining could be accomplished by simply dipping the filter into the different incubation media. The cells could be dehydrated and embedded in Epon 812 on the filter. After polymerization the embedded filter was sawn into small blocks and the cell layer was sectioned tangentially on an ultramicrotome. This method also seems to be applicable to other histochemical studies on single cells.", "contents": "A simple technique for supporting single cells in electron microscopic immunocytochemistry and embedding. Cell suspensions of rat anterior pituitaries were filtered with a polycarbonate filter (pore size 3 micron) and fixed on the filter. After fixation the cells were adherent to the filter and immunocytochemical staining could be accomplished by simply dipping the filter into the different incubation media. The cells could be dehydrated and embedded in Epon 812 on the filter. After polymerization the embedded filter was sawn into small blocks and the cell layer was sectioned tangentially on an ultramicrotome. This method also seems to be applicable to other histochemical studies on single cells."}
{"id": "PMID:199564", "title": "Role of conducting airways in partial separation of inhaled gas mixtures.", "content": "A positive (hollow) cast of the bronchial tree was made from a pig's lung. Gas mixtures containing sulfur hexafluoride (SF6) and helium (He), and SF6 and argon (Ar), were blown down the cast at two different flows, the cast having first been filled with air. Gas was sampled by a mass spectrometer probe from 1-mm-diam branches situated on short, medium, and long pathways. The front of the SF6 appeared in advance of the fronts of the He and the Ar. This relative advancement was greater a) with the SF6/He mixture than with the SF6/Ar mixture; b) at slower flows; and c) on longer pathways. With reverse flow up the cast using SF6/He there was little differences between the arrival times of the two gas fronts at either flow. These results could be explained by the effects of Taylor dispersion on gases having different diffusion coefficients.", "contents": "Role of conducting airways in partial separation of inhaled gas mixtures. A positive (hollow) cast of the bronchial tree was made from a pig's lung. Gas mixtures containing sulfur hexafluoride (SF6) and helium (He), and SF6 and argon (Ar), were blown down the cast at two different flows, the cast having first been filled with air. Gas was sampled by a mass spectrometer probe from 1-mm-diam branches situated on short, medium, and long pathways. The front of the SF6 appeared in advance of the fronts of the He and the Ar. This relative advancement was greater a) with the SF6/He mixture than with the SF6/Ar mixture; b) at slower flows; and c) on longer pathways. With reverse flow up the cast using SF6/He there was little differences between the arrival times of the two gas fronts at either flow. These results could be explained by the effects of Taylor dispersion on gases having different diffusion coefficients."}
{"id": "PMID:199565", "title": "Penetration of inhaled He and SF6 into alveolar space at low tidal volumes.", "content": "To study mixing of inspired gas with lung gas, penetration of simultaneously inspired helium (He) and sulfur hexafluoride (SF6) into alveolar space was determined in normal subjects at low tidal volumes (from 50 to 500 ml) and at varied lung volumes and speeds of inspiration/expiration. The volume of inspired gas reaching the alveolar space, termed alveolar-tidal volume, VTA, was calculated from preinspiratory lung volume, inspired volume, and inspired and expired alveolar test gas concentrations. The difference between the VTA values calculated for He and SF6, VTA(He) - VTA(SF6), was influenced by tidal volume, lung volume, and the speed of inspiration/expiration, but it was always positive. The results are qualitatively explainable on the basis of easier diffusive mixing of He in lung airways compared with SF6. Since Taylor dispersion would produce deeper penetration, and therefore higher VTA, for a less diffusible gas the results provide no evidence for its implication in pulmonary gas exchange.", "contents": "Penetration of inhaled He and SF6 into alveolar space at low tidal volumes. To study mixing of inspired gas with lung gas, penetration of simultaneously inspired helium (He) and sulfur hexafluoride (SF6) into alveolar space was determined in normal subjects at low tidal volumes (from 50 to 500 ml) and at varied lung volumes and speeds of inspiration/expiration. The volume of inspired gas reaching the alveolar space, termed alveolar-tidal volume, VTA, was calculated from preinspiratory lung volume, inspired volume, and inspired and expired alveolar test gas concentrations. The difference between the VTA values calculated for He and SF6, VTA(He) - VTA(SF6), was influenced by tidal volume, lung volume, and the speed of inspiration/expiration, but it was always positive. The results are qualitatively explainable on the basis of easier diffusive mixing of He in lung airways compared with SF6. Since Taylor dispersion would produce deeper penetration, and therefore higher VTA, for a less diffusible gas the results provide no evidence for its implication in pulmonary gas exchange."}
{"id": "PMID:199566", "title": "Control of liver size in heat-acclimated hamsters.", "content": "In the hamster, heat acclimation reduces liver weight more than it does body weight. Therefore, liver weight constitutes a lower percentage of body weight during exposure to high ambient temperature. This change is not a result of dehydration since water content of the whole body and of the liver is not altered during heat acclimation. However, changes in lactic dehydrogenase isozyme proportions indicate a higher rate of liver degradation during the first 2 wk of heat exposure. These changes are accompanied by enhancement of DNA synthesis which is found to be elevated during the early period of heat exposure and later to fall to the control levels. The enhanced DNA synthesis might be a result of a high rate of tissue regeneration which probably takes place in the organ following the commencement of the degradative processes as was suggested in partial hepatectomy. Since the activity of DNA synthesis is negatively correlated with cyclic AMP levels, it is suggested that cyclic AMP plays some role in controlling hepatic DNA synthesis during heat acclimation.", "contents": "Control of liver size in heat-acclimated hamsters. In the hamster, heat acclimation reduces liver weight more than it does body weight. Therefore, liver weight constitutes a lower percentage of body weight during exposure to high ambient temperature. This change is not a result of dehydration since water content of the whole body and of the liver is not altered during heat acclimation. However, changes in lactic dehydrogenase isozyme proportions indicate a higher rate of liver degradation during the first 2 wk of heat exposure. These changes are accompanied by enhancement of DNA synthesis which is found to be elevated during the early period of heat exposure and later to fall to the control levels. The enhanced DNA synthesis might be a result of a high rate of tissue regeneration which probably takes place in the organ following the commencement of the degradative processes as was suggested in partial hepatectomy. Since the activity of DNA synthesis is negatively correlated with cyclic AMP levels, it is suggested that cyclic AMP plays some role in controlling hepatic DNA synthesis during heat acclimation."}
{"id": "PMID:199567", "title": "Isolated, ventilated, perfused newborn rabbit lung preparation and its assessment.", "content": "To achieve an isolated, ventilated, perfused newborn rabbit lung preparation, newborn rabbits are anesthetized and ventilated. The pulmonary vasculature is perfused with a Krebs-Ringer bicarbonate solution containing glucose and plasma expanders, and the lungs are isolated in a 37 degrees C chamber at 100% humidity. The success of a perfusion is evaluated on three levels. 1) Visual. 2)mechanical: a, drop in flow of greater than 20% indicates failure; b, an increase of more than 25% of the initial lung weight indicates fluid accumulation and failure. 3) Biochemical: a, the endogenous ATP concentration after perfusion; b, the level of the enzyme choline phosphotransferase (CPT) after perfusion. Isolated, perfused, ventilated newborn rabbit lungs maintained for 4 h with no changes in the monitored physical and mechanical parameters have an endogenous ATP level of 1.06 +/- 0.06 (2 SD) mumol ATP/mg wet weight and a CPT level of 1.34 +/-0.15 (2 SD nmol [14C]CDP-choline per milligram protein in 30 min. These values are stable at a level lower than observed in intact, hypoxic, newborn rabbit's lungs. In constrast, if perfusion is maintained after any of the monitored criteria indicate failure, the endogenous ATP concentration and CPT activity are significantly depressed.", "contents": "Isolated, ventilated, perfused newborn rabbit lung preparation and its assessment. To achieve an isolated, ventilated, perfused newborn rabbit lung preparation, newborn rabbits are anesthetized and ventilated. The pulmonary vasculature is perfused with a Krebs-Ringer bicarbonate solution containing glucose and plasma expanders, and the lungs are isolated in a 37 degrees C chamber at 100% humidity. The success of a perfusion is evaluated on three levels. 1) Visual. 2)mechanical: a, drop in flow of greater than 20% indicates failure; b, an increase of more than 25% of the initial lung weight indicates fluid accumulation and failure. 3) Biochemical: a, the endogenous ATP concentration after perfusion; b, the level of the enzyme choline phosphotransferase (CPT) after perfusion. Isolated, perfused, ventilated newborn rabbit lungs maintained for 4 h with no changes in the monitored physical and mechanical parameters have an endogenous ATP level of 1.06 +/- 0.06 (2 SD) mumol ATP/mg wet weight and a CPT level of 1.34 +/-0.15 (2 SD nmol [14C]CDP-choline per milligram protein in 30 min. These values are stable at a level lower than observed in intact, hypoxic, newborn rabbit's lungs. In constrast, if perfusion is maintained after any of the monitored criteria indicate failure, the endogenous ATP concentration and CPT activity are significantly depressed."}
{"id": "PMID:199571", "title": "Respiratory competence of Dictyostelium discoideum spores.", "content": "Analysis of the respiratory chain of spores of Dictyostelium discoideum, which lack a cyanide-sensitive respiration, indicated that cytochromes a-a3, b, and c-c1 are present at levels identical to those found in the vegetative amoebae. The specific activities of enzymes of both the respiratory chain and the citric acid cycle in the 600 x g supernatant fraction of sonically treated spores were at least as high as in similar preparations of amoebae. The activities of glutamic dehydrogenase and oligomycin-sensitive adenosine triphosphatase were reduced in the spores 30 and 56%, respectively. Intact spores appeared to lack a cyanide-sensitive respiration as a result of inadequate quantities of respiratory substrate and, more importantly, as a result of a lack of the cofactor nicotinamide adenine dinucleotide. The emergence phase of spore germination was sensitive to the antibiotic chloramphenicol, which is a specific inhibitor of mitochondrial protein synthesis. It is concluded that germination requires the early synthesis of oxidized nicotinamide adenine dinucleotide and generation of respiratory substrates and one or more mitochondrially synthesized proteins.", "contents": "Respiratory competence of Dictyostelium discoideum spores. Analysis of the respiratory chain of spores of Dictyostelium discoideum, which lack a cyanide-sensitive respiration, indicated that cytochromes a-a3, b, and c-c1 are present at levels identical to those found in the vegetative amoebae. The specific activities of enzymes of both the respiratory chain and the citric acid cycle in the 600 x g supernatant fraction of sonically treated spores were at least as high as in similar preparations of amoebae. The activities of glutamic dehydrogenase and oligomycin-sensitive adenosine triphosphatase were reduced in the spores 30 and 56%, respectively. Intact spores appeared to lack a cyanide-sensitive respiration as a result of inadequate quantities of respiratory substrate and, more importantly, as a result of a lack of the cofactor nicotinamide adenine dinucleotide. The emergence phase of spore germination was sensitive to the antibiotic chloramphenicol, which is a specific inhibitor of mitochondrial protein synthesis. It is concluded that germination requires the early synthesis of oxidized nicotinamide adenine dinucleotide and generation of respiratory substrates and one or more mitochondrially synthesized proteins."}
{"id": "PMID:199572", "title": "Characterization of a novel thiosulfate-forming enzyme isolated from Desulfovibrio vulgaris.", "content": "An enzyme that formed thiosulfate from bisulfite and trithionate was purified from extracts of Desulfovibrio vulgaris. This enzyme, designated as \"thiosulfate-forming\" enzyme, required the presence of both bisulfite and trithionate. Various 35S-labeling studies showed that thiosulfate was formed from bisulfite and the inner sulfur atom of trithionate. This involved a nucleophilic attack by the bisulfite ion, resulting in the displacement of the two outer sulfonate groups of trithionate that recycled to participate as free bisulfite in subsequent reactions. This reaction required a reduction, presumably by a concerted mechanism with thiosulfate formation. The natural electron carrier cytochrome c3 participated in this reductive formation of thiosulfate. This reaction was coupled to the bisulfite reductase-catalyzed reaction, which resulted in the reconstruction of a thiosulfate-forming pathway from bisulfite.", "contents": "Characterization of a novel thiosulfate-forming enzyme isolated from Desulfovibrio vulgaris. An enzyme that formed thiosulfate from bisulfite and trithionate was purified from extracts of Desulfovibrio vulgaris. This enzyme, designated as \"thiosulfate-forming\" enzyme, required the presence of both bisulfite and trithionate. Various 35S-labeling studies showed that thiosulfate was formed from bisulfite and the inner sulfur atom of trithionate. This involved a nucleophilic attack by the bisulfite ion, resulting in the displacement of the two outer sulfonate groups of trithionate that recycled to participate as free bisulfite in subsequent reactions. This reaction required a reduction, presumably by a concerted mechanism with thiosulfate formation. The natural electron carrier cytochrome c3 participated in this reductive formation of thiosulfate. This reaction was coupled to the bisulfite reductase-catalyzed reaction, which resulted in the reconstruction of a thiosulfate-forming pathway from bisulfite."}
{"id": "PMID:199573", "title": "Intracellular distribution of enzymes of phospholipid metabolism in several gram-negative bacteria.", "content": "Cell-free extracts of Salmonella typhimurium, Serratia marcescens, Enterobacter aerogenes, and Micrococcus cerificans contained the following enzymatic activities related to phospholipid metabolism: cytidine 5'-diphospho-1,2-diacyl-sn-glycerol (CDP-diglyceride):l-serine O-phosphatidyltransferase (phosphatidylserine synthase), phosphatidylserine decarboxylase, CDP-diglyceride:sn-glycero-3-phosphate phosphatidyltransferase (phosphatidylglycerophosphate synthase), phosphatidylglycerophosphate phosphatase, and CDP-diglyceride hydrolase. The intracellular distribution of these enzymatic activities as determined by sucrose density gradient centrifugation of cell-free extracts was shown to be similar in each species investigated. The phosphatidylserine decarboxylase, phosphatidylglycerophosphate synthase, and CDP-diglyceride hydrolase activities were all associated with the cell envelope fraction, whereas the phosphatidylserine synthase activity was associated mainly with the ribosomal fraction. These enzymatic activities are comparable and have an intracellular distribution similar to those found in Escherichia coli cell-free extracts. Therefore, the pathways established for phospholipid biosynthesis in E. coli can also account for the synthesis of the major phospholipids (phosphatidylethanolamine and phosphatidylglycerol) in several other gram-negative organisms. In addition, the unusual ribosomal association of the phosphatidylserine synthase from E. coli (Raetz and Kennedy, J. Biol. Chem. 247:2008-2014, 1972) appears to be a general property for this activity in several other bacterial species.", "contents": "Intracellular distribution of enzymes of phospholipid metabolism in several gram-negative bacteria. Cell-free extracts of Salmonella typhimurium, Serratia marcescens, Enterobacter aerogenes, and Micrococcus cerificans contained the following enzymatic activities related to phospholipid metabolism: cytidine 5'-diphospho-1,2-diacyl-sn-glycerol (CDP-diglyceride):l-serine O-phosphatidyltransferase (phosphatidylserine synthase), phosphatidylserine decarboxylase, CDP-diglyceride:sn-glycero-3-phosphate phosphatidyltransferase (phosphatidylglycerophosphate synthase), phosphatidylglycerophosphate phosphatase, and CDP-diglyceride hydrolase. The intracellular distribution of these enzymatic activities as determined by sucrose density gradient centrifugation of cell-free extracts was shown to be similar in each species investigated. The phosphatidylserine decarboxylase, phosphatidylglycerophosphate synthase, and CDP-diglyceride hydrolase activities were all associated with the cell envelope fraction, whereas the phosphatidylserine synthase activity was associated mainly with the ribosomal fraction. These enzymatic activities are comparable and have an intracellular distribution similar to those found in Escherichia coli cell-free extracts. Therefore, the pathways established for phospholipid biosynthesis in E. coli can also account for the synthesis of the major phospholipids (phosphatidylethanolamine and phosphatidylglycerol) in several other gram-negative organisms. In addition, the unusual ribosomal association of the phosphatidylserine synthase from E. coli (Raetz and Kennedy, J. Biol. Chem. 247:2008-2014, 1972) appears to be a general property for this activity in several other bacterial species."}
{"id": "PMID:199574", "title": "Sulfate uptake in Saccharomyces cerevisiae: biochemical and genetic study.", "content": "Sulfate uptake is the first step of the sulfate assimilation pathway, which has been shown in our laboratory to be part of the methionine biosynthetic pathway. Kinetic study of sulfate uptake has shown a biphasic curve in a Lineweaver-Burk plot. The analysis of this plot indicates that two enzymes participate in sulfate uptake. One (permease I) has a high affinity for the substrate (K(m) = 0.005 mM); the other (permease II) shows a much lower affinity for sulfate (K(m) = 0.35 mM). Regulation of the synthesis of both permeases is under the control of exogenous methionine or S-adenosylmethionine. It was shown, moreover, that synthesis of sulfate permeases is coordinated with the synthesis of the other methionine biosynthetic enzymes thus far studied in our laboratory. An additional specific regulation of sulfate permeases by inhibition of their activity by endogenous sulfate and adenosyl phosphosulfate (an intermediate metabolite in sulfate assimilation) has been shown. A mutant unable to concentrate sulfate has been selected. This strain carried mutations in two independent genes. These two mutations, separated in two different strains, lead to modified kinetics of sulfate uptake. The study of these strains leads us to postulate that there is an interaction in situ between the products of these two genes.", "contents": "Sulfate uptake in Saccharomyces cerevisiae: biochemical and genetic study. Sulfate uptake is the first step of the sulfate assimilation pathway, which has been shown in our laboratory to be part of the methionine biosynthetic pathway. Kinetic study of sulfate uptake has shown a biphasic curve in a Lineweaver-Burk plot. The analysis of this plot indicates that two enzymes participate in sulfate uptake. One (permease I) has a high affinity for the substrate (K(m) = 0.005 mM); the other (permease II) shows a much lower affinity for sulfate (K(m) = 0.35 mM). Regulation of the synthesis of both permeases is under the control of exogenous methionine or S-adenosylmethionine. It was shown, moreover, that synthesis of sulfate permeases is coordinated with the synthesis of the other methionine biosynthetic enzymes thus far studied in our laboratory. An additional specific regulation of sulfate permeases by inhibition of their activity by endogenous sulfate and adenosyl phosphosulfate (an intermediate metabolite in sulfate assimilation) has been shown. A mutant unable to concentrate sulfate has been selected. This strain carried mutations in two independent genes. These two mutations, separated in two different strains, lead to modified kinetics of sulfate uptake. The study of these strains leads us to postulate that there is an interaction in situ between the products of these two genes."}
{"id": "PMID:199575", "title": "Ribonucleic acid polymerase mutant of Escherichia coli defective in flagella formation.", "content": "Escherichia coli K-12 mutants that are resistant to bacteriophage chi, defective in motility, and unable to grow at high temperature (42 degrees C) were isolated from among those selected for rifampin resistance at low temperature (30 degrees C) after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. Genetic analysis of one such mutant indicated the presence of two mutations that probably affect the beta subunit of ribonucleic acid (RNA) polymerase: one (rif) causing rifampin resistance and the other (Ts-74) conferring resistance to phage chi (and loss of motility) and temperature sensitivity for growth. Observations with an electron microscope revealed that the number of flagella per mutant cell was significantly reduced, suggesting that the Ts-74 mutation somehow affected flagella formation at the permissive temperature. When a mutant culture was transferred from 30 to 42 degrees C, deoxyribonucleic acid synthesis accelerated normally, but RNA or protein synthesis was enhanced relatively little. The rate of synthesis of beta and beta' subunits of RNA polymerase was low even at 30 degrees C and was further reduced at 42 degrees C, in contrast to the parental wild-type strain. Expression of the lactose and other sugar fermentation operons, as well as lysogenization with phage lambda, occurred normally at 30 degrees C, suggesting that the mutation does not cause general shut-off of gene expression regulated by cyclic adenosine 3',5'-monophosphate.", "contents": "Ribonucleic acid polymerase mutant of Escherichia coli defective in flagella formation. Escherichia coli K-12 mutants that are resistant to bacteriophage chi, defective in motility, and unable to grow at high temperature (42 degrees C) were isolated from among those selected for rifampin resistance at low temperature (30 degrees C) after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. Genetic analysis of one such mutant indicated the presence of two mutations that probably affect the beta subunit of ribonucleic acid (RNA) polymerase: one (rif) causing rifampin resistance and the other (Ts-74) conferring resistance to phage chi (and loss of motility) and temperature sensitivity for growth. Observations with an electron microscope revealed that the number of flagella per mutant cell was significantly reduced, suggesting that the Ts-74 mutation somehow affected flagella formation at the permissive temperature. When a mutant culture was transferred from 30 to 42 degrees C, deoxyribonucleic acid synthesis accelerated normally, but RNA or protein synthesis was enhanced relatively little. The rate of synthesis of beta and beta' subunits of RNA polymerase was low even at 30 degrees C and was further reduced at 42 degrees C, in contrast to the parental wild-type strain. Expression of the lactose and other sugar fermentation operons, as well as lysogenization with phage lambda, occurred normally at 30 degrees C, suggesting that the mutation does not cause general shut-off of gene expression regulated by cyclic adenosine 3',5'-monophosphate."}
{"id": "PMID:199576", "title": "2-Hydroxypyridine metabolism and pigment formation in three Arthrobacter species.", "content": "Three species of the genus Arthrobacter, A. crystallopoietes, A. pyridinolis, and A. viridescens, have the capabilities to utilize 2-hydroxypyridine (2-HP) as the sole source of carbon and nitrogen for growth and to produce an extracellular crystalline pigment from this substrate. Degradation of 2-HP by cell-free extracts requires the presence of both reduced nicotinamide adenine dinucleotide and molecular oxygen and is stimulated by flavin mononucleotide, suggesting the presence of a monooxygenase activity in the extract. Loss of the ability to produce pigment at a high spontaneous frequency, 0.26% loss per generation, is observed only with A. crystallopoietes and can be visualized by the presence of sectored and fully nonpigmented colonies on solid media containing 2-HP. Concomitant with the loss of pigment-producing character are both loss of ability to utilize 2-HP for growth and oxidation of 2-HP by cell-free extracts. These three 2-HP-associated characteristics also are lost simultaneously by treating cultures of A. crystallopoietes with curing agents, such as acridine orange and mitomycin C, but are not curable in A. pyridinolis or A. viridescens. All nonpigmented strains of A. crystallopoietes are nonrevertible for these properties. These data suggest that 2-HP-related characteristics are plasmid determined in A. crystallopoietes but not in A. pyridinolis and A. viridescens. A survey for the presence of plasmids in these three species and two physiologically unrelated species, A. globiformis and A. atrocyaneus, revealed plasmid material only in A. globiformis and A. crystallopoietes.", "contents": "2-Hydroxypyridine metabolism and pigment formation in three Arthrobacter species. Three species of the genus Arthrobacter, A. crystallopoietes, A. pyridinolis, and A. viridescens, have the capabilities to utilize 2-hydroxypyridine (2-HP) as the sole source of carbon and nitrogen for growth and to produce an extracellular crystalline pigment from this substrate. Degradation of 2-HP by cell-free extracts requires the presence of both reduced nicotinamide adenine dinucleotide and molecular oxygen and is stimulated by flavin mononucleotide, suggesting the presence of a monooxygenase activity in the extract. Loss of the ability to produce pigment at a high spontaneous frequency, 0.26% loss per generation, is observed only with A. crystallopoietes and can be visualized by the presence of sectored and fully nonpigmented colonies on solid media containing 2-HP. Concomitant with the loss of pigment-producing character are both loss of ability to utilize 2-HP for growth and oxidation of 2-HP by cell-free extracts. These three 2-HP-associated characteristics also are lost simultaneously by treating cultures of A. crystallopoietes with curing agents, such as acridine orange and mitomycin C, but are not curable in A. pyridinolis or A. viridescens. All nonpigmented strains of A. crystallopoietes are nonrevertible for these properties. These data suggest that 2-HP-related characteristics are plasmid determined in A. crystallopoietes but not in A. pyridinolis and A. viridescens. A survey for the presence of plasmids in these three species and two physiologically unrelated species, A. globiformis and A. atrocyaneus, revealed plasmid material only in A. globiformis and A. crystallopoietes."}
{"id": "PMID:199577", "title": "Requirement of cyclic adenosine 3',5'-monophosphate for the thermosensitive effects of Rts1 in a cyclic adenosine 3',5'-monophosphate-less mutant of Escherichia coli.", "content": "Previous publications showed that a covalently closed circular (CCC) Rts1 plasmid deoxyribonucleic acid (DNA) that confers kanamycin resistance upon the host bacteria inhibits host growth at 42 degrees C but not at 32 degrees C. At 42 degrees C, the CCC Rts1 DNA is not formed, and cells without plasmids emerge. To investigate the possible role of cyclic adenosine 3',5'-monophosphate (cAMP) in the action of Rts1 on host bacteria, Rts1 was placed in an Escherichia coli mutant (CA7902) that lacks adenylate cyclase or in E. coli PP47 (a mutant lacking cAMP receptor protein). Rts1 did not exert the thermosensitive effect on these cells, and CCC Rts1 DNA was formed even at 42 degrees C. Upon addition of cAMP to E. coli CA7902(Rts1), cell growth and formation of CCC Rts1 DNA were inhibited at 42 degrees C. The addition of cAMP to E. coli PP47(Rts1) did not cause inhibitory effects on either cell growth or CCC Rts1 DNA formation at 42 degrees C. The inhibitory effect of cAMP on E. coli CA7902(Rts1) is specific to this cyclic nucleotide, and other cyclic nucleotides such as cyclic guanosine 3',5'-monophosphate did not have the effect. For this inhibitory effect, cells have to be preincubated with cAMP; the presence of cAMP at the time of CCC Rts1 DNA formation is not enough for the inhibitory effect. If the cells are preincubated with cAMP, one can remove cAMP during the [(3)H]thymidine pulse and still observe its inhibitory effect on the formation of CCC Rts1 DNA. The presence of chloramphenicol during this preincubation period abolished the inhibitory effect of cAMP. These observations suggest that cAMP is necessary to induce synthesis of a protein that inhibits CCC Rts1 DNA formation and cell growth at 42 degrees C.", "contents": "Requirement of cyclic adenosine 3',5'-monophosphate for the thermosensitive effects of Rts1 in a cyclic adenosine 3',5'-monophosphate-less mutant of Escherichia coli. Previous publications showed that a covalently closed circular (CCC) Rts1 plasmid deoxyribonucleic acid (DNA) that confers kanamycin resistance upon the host bacteria inhibits host growth at 42 degrees C but not at 32 degrees C. At 42 degrees C, the CCC Rts1 DNA is not formed, and cells without plasmids emerge. To investigate the possible role of cyclic adenosine 3',5'-monophosphate (cAMP) in the action of Rts1 on host bacteria, Rts1 was placed in an Escherichia coli mutant (CA7902) that lacks adenylate cyclase or in E. coli PP47 (a mutant lacking cAMP receptor protein). Rts1 did not exert the thermosensitive effect on these cells, and CCC Rts1 DNA was formed even at 42 degrees C. Upon addition of cAMP to E. coli CA7902(Rts1), cell growth and formation of CCC Rts1 DNA were inhibited at 42 degrees C. The addition of cAMP to E. coli PP47(Rts1) did not cause inhibitory effects on either cell growth or CCC Rts1 DNA formation at 42 degrees C. The inhibitory effect of cAMP on E. coli CA7902(Rts1) is specific to this cyclic nucleotide, and other cyclic nucleotides such as cyclic guanosine 3',5'-monophosphate did not have the effect. For this inhibitory effect, cells have to be preincubated with cAMP; the presence of cAMP at the time of CCC Rts1 DNA formation is not enough for the inhibitory effect. If the cells are preincubated with cAMP, one can remove cAMP during the [(3)H]thymidine pulse and still observe its inhibitory effect on the formation of CCC Rts1 DNA. The presence of chloramphenicol during this preincubation period abolished the inhibitory effect of cAMP. These observations suggest that cAMP is necessary to induce synthesis of a protein that inhibits CCC Rts1 DNA formation and cell growth at 42 degrees C."}
{"id": "PMID:199578", "title": "Membrane phospholipid synthesis and phenotypic correlation of an Escherichia coli pss mutant.", "content": "A pair of putatively isogenic pss(Ts) and pss+ (phosphatidylserine synthetase structural gene) strains was constructed and analyzed, together with the revertants, for the physiological consequences of cessation of the optimal synthesis of phosphatidylethanolamine (PE). Their in vivo and in vitro abilities to synthetize PE and the growth rates at different temperatures were determined. The rate of PE synthesis by OS2101 pss(Ts) was inversely related to the culture temperature. OS2101 in a low-salt broth medium stopped division and formed filamentous cells with declining viability upon the elevation of culture temperature from 27 to 42 or 44 degrees C, whereas the syntheses of deoxyribonucleic acid, ribonucleic acid, and protein were not affected. Proper concentrations of cations such as Na+, K+, NH4+, and Mg2+ or of sucrose could remedy the division and growth of OS2101 at the restrictive temperature without restoring normal PE synthesis. A remedial effect other than osmotic protection of these effectors and an adaptive regulatory mechanism for PE formation are suggested.", "contents": "Membrane phospholipid synthesis and phenotypic correlation of an Escherichia coli pss mutant. A pair of putatively isogenic pss(Ts) and pss+ (phosphatidylserine synthetase structural gene) strains was constructed and analyzed, together with the revertants, for the physiological consequences of cessation of the optimal synthesis of phosphatidylethanolamine (PE). Their in vivo and in vitro abilities to synthetize PE and the growth rates at different temperatures were determined. The rate of PE synthesis by OS2101 pss(Ts) was inversely related to the culture temperature. OS2101 in a low-salt broth medium stopped division and formed filamentous cells with declining viability upon the elevation of culture temperature from 27 to 42 or 44 degrees C, whereas the syntheses of deoxyribonucleic acid, ribonucleic acid, and protein were not affected. Proper concentrations of cations such as Na+, K+, NH4+, and Mg2+ or of sucrose could remedy the division and growth of OS2101 at the restrictive temperature without restoring normal PE synthesis. A remedial effect other than osmotic protection of these effectors and an adaptive regulatory mechanism for PE formation are suggested."}
{"id": "PMID:199579", "title": "Icosahedral inclusions (carboxysomes) of Nitrobacter agilis.", "content": "The icosahedral bodies of Nitrobacter agilis are about 120 nm in diameter and, as viewed by electron microscopy, consist of an outer shell enclosing 10-nm particles. The inner 10-nm particle is the enzyme D-ribulose 1,5-bisphosphate carboxylase. The bodies isolated from cells incubated 1 month without nitrite had a specific activity for the enzyme of 0.54 mu mol of CO2 fixed per min per mg of protein.", "contents": "Icosahedral inclusions (carboxysomes) of Nitrobacter agilis. The icosahedral bodies of Nitrobacter agilis are about 120 nm in diameter and, as viewed by electron microscopy, consist of an outer shell enclosing 10-nm particles. The inner 10-nm particle is the enzyme D-ribulose 1,5-bisphosphate carboxylase. The bodies isolated from cells incubated 1 month without nitrite had a specific activity for the enzyme of 0.54 mu mol of CO2 fixed per min per mg of protein."}
{"id": "PMID:199580", "title": "Production of large amounts of acetate during germination of Bacillus megaterium spores in the absence of exogenous carbon sources.", "content": "When Bacillus megaterium spores germinate in the absence of an exogenous carbon source, the first minutes of germination are accompanied by production of large amounts (approximately 70 nmol/mg of dry spores) of acetate and much smaller amounts of pyruvate and lactate. The majority of these compounds are excreted into the medium. Exogenous pyruvate and alanine are also converted to CO2 and acetate by germinating spores, presumably by using the pyruvate dehydrogenase that is present in dormant spores. These data suggest that the 3-phosphoglyceric acid stores in the dormant spore and alanine generated by proteolysis early in germination can be catabolized to acetate during germination with production of large amounts of reduced nicotinamide adenine dinucleotide, acetyl coenzyme A, and adenosine 5'-triphosphate.", "contents": "Production of large amounts of acetate during germination of Bacillus megaterium spores in the absence of exogenous carbon sources. When Bacillus megaterium spores germinate in the absence of an exogenous carbon source, the first minutes of germination are accompanied by production of large amounts (approximately 70 nmol/mg of dry spores) of acetate and much smaller amounts of pyruvate and lactate. The majority of these compounds are excreted into the medium. Exogenous pyruvate and alanine are also converted to CO2 and acetate by germinating spores, presumably by using the pyruvate dehydrogenase that is present in dormant spores. These data suggest that the 3-phosphoglyceric acid stores in the dormant spore and alanine generated by proteolysis early in germination can be catabolized to acetate during germination with production of large amounts of reduced nicotinamide adenine dinucleotide, acetyl coenzyme A, and adenosine 5'-triphosphate."}
{"id": "PMID:199581", "title": "A new method for measurement of cyclic AMP phosphodiesterase activity.", "content": "The extreme sensitivity of chicken muscle fructose 1,6-bisphosphatase to inhibition by 5'-AMP has been utilized to develop a new method for the assay of cAMP phosphodiesterase activity. In this method, the substrate (cAMP) is first incubated with phosphodiesterase and the amount of 5'-AMP formed is then determined by measuring the degree of inhibition of fructose 1'6-bisphosphatase activity. The present method conveniently employs the spectrophotometric technique and is sensitive enough to detect the conversion of 50 pmol of cAMP to 5'-AMP in 1 ml of reaction mixture. This method is considered particularly valuable for those laboratories that are not equipped with facilities for measuring radioactivity.", "contents": "A new method for measurement of cyclic AMP phosphodiesterase activity. The extreme sensitivity of chicken muscle fructose 1,6-bisphosphatase to inhibition by 5'-AMP has been utilized to develop a new method for the assay of cAMP phosphodiesterase activity. In this method, the substrate (cAMP) is first incubated with phosphodiesterase and the amount of 5'-AMP formed is then determined by measuring the degree of inhibition of fructose 1'6-bisphosphatase activity. The present method conveniently employs the spectrophotometric technique and is sensitive enough to detect the conversion of 50 pmol of cAMP to 5'-AMP in 1 ml of reaction mixture. This method is considered particularly valuable for those laboratories that are not equipped with facilities for measuring radioactivity."}
{"id": "PMID:199582", "title": "Phosphatidylcholine substrate specificity of lecithin: cholestrol acyltransferase-in high density lipoproteins and in lipids dispersions.", "content": "Lecithin: cholesterol acyltransferase (LCAT) was more highly activated by apolipoprotein A-I (apoA-I) with dimyristoyl phosphatidylcholine (DMPC) than with dilinoleoyl phosphatidylcholine (DLPC) when lipid dispersion of cholesterol and each phosphatidylcholine was used as a substrate. When the enzyme reactions were activated by whole apolipoproteins of high density lipoproteins (HDL), DLPC was more available to the LCAT reaction than DMPC with high concentrations of apoHDL in an incubation mixture. However,  no detectable enzyme reaction was observed with dipalmitoyl phosphatidylcholine (DPPC) under both conditions. On the other hand, all of these phosphatidylcholines acted as substrates of LCAT when they were incorporated into HDL coupled to Sepharose. The order of their relative reactivities to cholesterol was DMPC, DPPC, AND DLPC under the conditions used.", "contents": "Phosphatidylcholine substrate specificity of lecithin: cholestrol acyltransferase-in high density lipoproteins and in lipids dispersions. Lecithin: cholesterol acyltransferase (LCAT) was more highly activated by apolipoprotein A-I (apoA-I) with dimyristoyl phosphatidylcholine (DMPC) than with dilinoleoyl phosphatidylcholine (DLPC) when lipid dispersion of cholesterol and each phosphatidylcholine was used as a substrate. When the enzyme reactions were activated by whole apolipoproteins of high density lipoproteins (HDL), DLPC was more available to the LCAT reaction than DMPC with high concentrations of apoHDL in an incubation mixture. However,  no detectable enzyme reaction was observed with dipalmitoyl phosphatidylcholine (DPPC) under both conditions. On the other hand, all of these phosphatidylcholines acted as substrates of LCAT when they were incorporated into HDL coupled to Sepharose. The order of their relative reactivities to cholesterol was DMPC, DPPC, AND DLPC under the conditions used."}
{"id": "PMID:199583", "title": "Purification and some properties of cytochrome c-552 from an extreme thermophile, Thermus thermophilus HB8.", "content": "A c-type cytochrome, cytochrome c-552, from a soluble fraction of an extreme thermophile, Thermus thermophilus HB8, was highly purified and its properties investigated. The absorption peaks were at 552, 522, and 417 nm in the reduced form, and at 408 nm in the oxidized form. The isoelectric point was at PH 10.8, the midpoint redox potential was about +0.23 V, and the molecular weight was about 15,000. The cytochrome c-552 was highly thermoresistant. The cytochrome reacted rapidly with pseudomonas aeruginosa nitrite reductase [EC 1.9.3.2], but slowly with bovine cytochrome oxidase [EC 1.9.3.1], yeast cytochrome c peroxidase [EC 1.11.1.5], or Nitrosomonas europaea hydroxylamine-cytochrome c reductase [EC 1.7.3.4].", "contents": "Purification and some properties of cytochrome c-552 from an extreme thermophile, Thermus thermophilus HB8. A c-type cytochrome, cytochrome c-552, from a soluble fraction of an extreme thermophile, Thermus thermophilus HB8, was highly purified and its properties investigated. The absorption peaks were at 552, 522, and 417 nm in the reduced form, and at 408 nm in the oxidized form. The isoelectric point was at PH 10.8, the midpoint redox potential was about +0.23 V, and the molecular weight was about 15,000. The cytochrome c-552 was highly thermoresistant. The cytochrome reacted rapidly with pseudomonas aeruginosa nitrite reductase [EC 1.9.3.2], but slowly with bovine cytochrome oxidase [EC 1.9.3.1], yeast cytochrome c peroxidase [EC 1.11.1.5], or Nitrosomonas europaea hydroxylamine-cytochrome c reductase [EC 1.7.3.4]."}
{"id": "PMID:199584", "title": "Inhibition by Mg2+ of the interaction of Ca2+ with spin-labeled g2 bound to myosin.", "content": "According to the measurement of ESR spectrum, Ca2+ induced conformational change of spin-labeled g2 bound to myosin in the presence of 1 mM Mg2+. The half-maximal changes were observed at pCa 6.8 and at pCa 3.7. Spin-labeled phosphorylated g2 bound to myosin showed one transition at pCa 4.5, which shifted to pCa 6.5 after the dephosphorylation  with E. coli alkaliphosphatase.", "contents": "Inhibition by Mg2+ of the interaction of Ca2+ with spin-labeled g2 bound to myosin. According to the measurement of ESR spectrum, Ca2+ induced conformational change of spin-labeled g2 bound to myosin in the presence of 1 mM Mg2+. The half-maximal changes were observed at pCa 6.8 and at pCa 3.7. Spin-labeled phosphorylated g2 bound to myosin showed one transition at pCa 4.5, which shifted to pCa 6.5 after the dephosphorylation  with E. coli alkaliphosphatase."}
{"id": "PMID:199589", "title": "Studies on the role of adenosine 3':5'-monophosphate in the activation of liver phosphorylase.", "content": "Crude extracts of rabbit liver, preincubated to promote the dephosphorylation of enzymes or other regulatory proteins, were used to study the role of cyclic AMP in the activation of glycogen phosphorylase. Inasmuch as endogenous liver phosphorylase was irreversibly altered by the preincubation procedure, crystalline skeletal muscle phosphorylase was used as the substrate in these studies. In the presence of magnesium ions and ATP, phosphorylase b was converted to phosphorylase a, and in an apparent biphasic process the phosphorylase a formed was subsequently converted to phosphorylase b. In the presence of adenosine 3':5'-monophosphate the rate of phosphorylase a formation and the maximal amount of phosphorylase a formed were increased. The cyclic AMP effect was enhanced by glucose-6-P and required the presence of glycogen. The catalytic subunit of cyclic AMP-dependent protein kinase could replace cyclic AMP in the stimulation of phosphorylase a formation. The effects of cyclic AMP or the catalytic subunit were shown to be due to stimulation of phosphorylase kinase rather than to inhibition of phosphorylase phosphatase. Preliminary fractionation experiments showed that it is possible to separate phosphorylase kinase catalytic activity from a factor or factors required for stimulation of its activation by the catalytic subunit.", "contents": "Studies on the role of adenosine 3':5'-monophosphate in the activation of liver phosphorylase. Crude extracts of rabbit liver, preincubated to promote the dephosphorylation of enzymes or other regulatory proteins, were used to study the role of cyclic AMP in the activation of glycogen phosphorylase. Inasmuch as endogenous liver phosphorylase was irreversibly altered by the preincubation procedure, crystalline skeletal muscle phosphorylase was used as the substrate in these studies. In the presence of magnesium ions and ATP, phosphorylase b was converted to phosphorylase a, and in an apparent biphasic process the phosphorylase a formed was subsequently converted to phosphorylase b. In the presence of adenosine 3':5'-monophosphate the rate of phosphorylase a formation and the maximal amount of phosphorylase a formed were increased. The cyclic AMP effect was enhanced by glucose-6-P and required the presence of glycogen. The catalytic subunit of cyclic AMP-dependent protein kinase could replace cyclic AMP in the stimulation of phosphorylase a formation. The effects of cyclic AMP or the catalytic subunit were shown to be due to stimulation of phosphorylase kinase rather than to inhibition of phosphorylase phosphatase. Preliminary fractionation experiments showed that it is possible to separate phosphorylase kinase catalytic activity from a factor or factors required for stimulation of its activation by the catalytic subunit."}
{"id": "PMID:199591", "title": "Synthesis and release of low density lipoproteins by the isolated perfused pig liver.", "content": "In previous studies, we have shown that a relatively large amount of low density lipoproteins is released into the perfusate during isolated pig liver perfusion. The present studies were done to determine the source of these lipoproteins. Breakdown of the very low density lipoproteins to low density lipoproteins by the perfusion apparatus or by hepatic catabolism was excluded by adding 125I very low density lipoproteins to the perfusate in the presence and absence of a liver and then measuring the radioactivity in the low density lipoprotein fraction after rate-zonal ultracentrifugation. Release of preformed low density, lipoproteins from the liver was investigated by injecting iodine-labeled low density lipoproteins in vivo several hours prior to perfusion of the liver and then measuring the release of labeled low density lipoproteins into the perfusate. It was shown that intact labeled low density lipoproteins were released by the perfused liver. De novo synthesis of the low density lipoproteins was established by measuring the incorporation of [1-14C]leucine into this lipoprotein fraction. The radioactivity in the low density lipoprotein fraction increased with time and accounted for 20 to 25% of the total radioactivity incorporated into all the lipoprotein fractions. The incorporation of [1-14C]leucine into the low density lipoproteins was confirmed by rate-zonal analysis. We conclude that the low density lipoproteins in the perfusate from pig liver perfusions were derived mainly from a preformed liver pool, but also partly from de novo synthesis by the liver.", "contents": "Synthesis and release of low density lipoproteins by the isolated perfused pig liver. In previous studies, we have shown that a relatively large amount of low density lipoproteins is released into the perfusate during isolated pig liver perfusion. The present studies were done to determine the source of these lipoproteins. Breakdown of the very low density lipoproteins to low density lipoproteins by the perfusion apparatus or by hepatic catabolism was excluded by adding 125I very low density lipoproteins to the perfusate in the presence and absence of a liver and then measuring the radioactivity in the low density lipoprotein fraction after rate-zonal ultracentrifugation. Release of preformed low density, lipoproteins from the liver was investigated by injecting iodine-labeled low density lipoproteins in vivo several hours prior to perfusion of the liver and then measuring the release of labeled low density lipoproteins into the perfusate. It was shown that intact labeled low density lipoproteins were released by the perfused liver. De novo synthesis of the low density lipoproteins was established by measuring the incorporation of [1-14C]leucine into this lipoprotein fraction. The radioactivity in the low density lipoprotein fraction increased with time and accounted for 20 to 25% of the total radioactivity incorporated into all the lipoprotein fractions. The incorporation of [1-14C]leucine into the low density lipoproteins was confirmed by rate-zonal analysis. We conclude that the low density lipoproteins in the perfusate from pig liver perfusions were derived mainly from a preformed liver pool, but also partly from de novo synthesis by the liver."}
{"id": "PMID:199592", "title": "Prolyl hydroxylase of earthworms. Substrate specificity of an enzyme from the subcuticular epithelium.", "content": "A relatively crude enzyme preparation derived from the subcuticular epithelium of earthworms catalyzed the formation of 4-hydroxyproline from prolyl residues in unhydroxylated natural collagens and in several synthetic collagen-like polypeptides. The specificity of hydroxylation differed from that of all vertebrate polyl hydroxylases in that (Gly-Pro-Ala)n was a much better substrate than (Gly-Ala-Pro)n. In contrast, however, only the so-called Y position proline (Gly-X-Y) was hydroxylated in Gly-Pro-Pro sequences derived either from natural collagen or from synthetic polypeptides; specificity of hydroxylation for the latter sequence is identical with that of the vertebrate enzymes. Little or no formation of 3-hydroxyproline could be demonstrated in preparations of the enzyme active as a 4-hydroxylase. In contrast with an earlier report from another laboratory, using a crude extract of earthworm body wall, we were unable to demonstrate either significant 3-hydroxyproline formation or efficient 4-hydroxylation of X position prolyl residues in synthetic polypeptides with the internal sequence Gly-Pro-Pro.", "contents": "Prolyl hydroxylase of earthworms. Substrate specificity of an enzyme from the subcuticular epithelium. A relatively crude enzyme preparation derived from the subcuticular epithelium of earthworms catalyzed the formation of 4-hydroxyproline from prolyl residues in unhydroxylated natural collagens and in several synthetic collagen-like polypeptides. The specificity of hydroxylation differed from that of all vertebrate polyl hydroxylases in that (Gly-Pro-Ala)n was a much better substrate than (Gly-Ala-Pro)n. In contrast, however, only the so-called Y position proline (Gly-X-Y) was hydroxylated in Gly-Pro-Pro sequences derived either from natural collagen or from synthetic polypeptides; specificity of hydroxylation for the latter sequence is identical with that of the vertebrate enzymes. Little or no formation of 3-hydroxyproline could be demonstrated in preparations of the enzyme active as a 4-hydroxylase. In contrast with an earlier report from another laboratory, using a crude extract of earthworm body wall, we were unable to demonstrate either significant 3-hydroxyproline formation or efficient 4-hydroxylation of X position prolyl residues in synthetic polypeptides with the internal sequence Gly-Pro-Pro."}
{"id": "PMID:199593", "title": "Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. I. Purification and characterization of an active enzyme from bovine cerebellum.", "content": "A protein kinase which phosphorylated histone and protamine was partially purified from bovine cerebellum. Casein and phosvitin were inert as substrates. The enzyme did not require any cyclic nucleotide. A sulfhydryl compound such as 2-mercaptoethanol, glutathione, or cysteine was necessary for the reaction. The optimum pH was 8.5 to 9.0 Km values for ATP and whole histone were 3.3 X 10(-6) M and 150 microgram/ml, respectively. The optimum concentration of Mg2+ varied with histone fractions employed; with H2B histone as substrate the enzyme was most active at 50 to 100 nM Mg2\", whereas with H1 and H2A histones the maximum activity was observed at 5 to 10 mM Mg2+ and with H3 and H4 histones the enzyme was active over a range of 5 to 75 mM Mg2+. The enzyme phosphorylated Ser-32 and Ser-36 in H2B histone and Ser-38 in H1 histone, although the reaction with Ser-36 in H2B histone was very slow. The molecular weight was 6.4 X 10(4). The sedimentation coefficient and Stokes radium were about 4.5 and 29 A, respectively. The enzyme showed heterogeneity upon isoelectrofocusing electrophoresis with isoelectric points of 5.6, 6.0, and 6.6. The enzyme was not inhibited by protein inhibitor nor by the regulatory subunit of cyclic AMP-dependent protein kinase. Preliminary analysis suggested that the enzyme was produced from its precursor protein by a limited proteolytic reaction.", "contents": "Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. I. Purification and characterization of an active enzyme from bovine cerebellum. A protein kinase which phosphorylated histone and protamine was partially purified from bovine cerebellum. Casein and phosvitin were inert as substrates. The enzyme did not require any cyclic nucleotide. A sulfhydryl compound such as 2-mercaptoethanol, glutathione, or cysteine was necessary for the reaction. The optimum pH was 8.5 to 9.0 Km values for ATP and whole histone were 3.3 X 10(-6) M and 150 microgram/ml, respectively. The optimum concentration of Mg2+ varied with histone fractions employed; with H2B histone as substrate the enzyme was most active at 50 to 100 nM Mg2\", whereas with H1 and H2A histones the maximum activity was observed at 5 to 10 mM Mg2+ and with H3 and H4 histones the enzyme was active over a range of 5 to 75 mM Mg2+. The enzyme phosphorylated Ser-32 and Ser-36 in H2B histone and Ser-38 in H1 histone, although the reaction with Ser-36 in H2B histone was very slow. The molecular weight was 6.4 X 10(4). The sedimentation coefficient and Stokes radium were about 4.5 and 29 A, respectively. The enzyme showed heterogeneity upon isoelectrofocusing electrophoresis with isoelectric points of 5.6, 6.0, and 6.6. The enzyme was not inhibited by protein inhibitor nor by the regulatory subunit of cyclic AMP-dependent protein kinase. Preliminary analysis suggested that the enzyme was produced from its precursor protein by a limited proteolytic reaction."}
{"id": "PMID:199595", "title": "Protein synthesis in 3T3 and SV40-transformed 3T3 cells. Activity of ribosomes and cytosol proteins in cell-free protein synthesis.", "content": "The activity of specific components involved in protein synthesis in 3T3 cells and its SV40-transformed derivative, SV3T3, were examined in a cell-free protein synthetic system, and the results correlated with previous studies, indicating that a decreasing rate of protein synthesis does not accompany the stationary phase of growth. We found that 3T3 and SV3T3 polysome preparations containing endogenous mRNA were equally efficient in supporting cell-free protein synthesis in this system. Further, the net protein synthesis observed was not altered by an increase in the population density of the cellular polysome source. The activity of the aminoacyl-tRNA synthetase enzymes from 3T3 and SV3T3 cells was examined in vitro after isolation by pH 5 precipitation and by ammonium sulfate fractionation. The activity of these preparations from stationary phase 3T3 and nonexponential phase SV3T3 cells was found to be approximately 3 times higher than the activity of fractions from the homologous exponential phase cell. However, at both growth stages, the SV3T3 preparations were 30 to 40 times more active than the 3T3 preparations. These findings may have implications for the different growth properties observed in the two cell types.", "contents": "Protein synthesis in 3T3 and SV40-transformed 3T3 cells. Activity of ribosomes and cytosol proteins in cell-free protein synthesis. The activity of specific components involved in protein synthesis in 3T3 cells and its SV40-transformed derivative, SV3T3, were examined in a cell-free protein synthetic system, and the results correlated with previous studies, indicating that a decreasing rate of protein synthesis does not accompany the stationary phase of growth. We found that 3T3 and SV3T3 polysome preparations containing endogenous mRNA were equally efficient in supporting cell-free protein synthesis in this system. Further, the net protein synthesis observed was not altered by an increase in the population density of the cellular polysome source. The activity of the aminoacyl-tRNA synthetase enzymes from 3T3 and SV3T3 cells was examined in vitro after isolation by pH 5 precipitation and by ammonium sulfate fractionation. The activity of these preparations from stationary phase 3T3 and nonexponential phase SV3T3 cells was found to be approximately 3 times higher than the activity of fractions from the homologous exponential phase cell. However, at both growth stages, the SV3T3 preparations were 30 to 40 times more active than the 3T3 preparations. These findings may have implications for the different growth properties observed in the two cell types."}
{"id": "PMID:199597", "title": "Partial purification and characterization of rat liver phenylalanine hydroxylase phosphatase.", "content": "A phosphatase which catalyzes the release of 32Pi from 32P-labeled phenylalanine hydroxylase has been purified about 50-fold from rat liver extracts. The phosphatase is able to catalyze the removal of only 70 to 80% of the 32Pi leaving about the same amount of Pi still bound to the hydroxylase as was originally present in the native enzyme. Dephosphorylation is accompanied by a corresponding loss in phenylalanine hydroxylase activity when the activity is measured with the natural cofactor, tetrahydrobiopterin, but not when measured with the synthetic cofactor, 6-methyltetrahydropterin. The partially purified phosphatase has very low activity toward p-nitrophenylphosphate, histone phosphate, and phosphorylase a. The activity toward these substrates has not been purified to the same extent as the phenylalanine hydroxylase phosphatase activity.", "contents": "Partial purification and characterization of rat liver phenylalanine hydroxylase phosphatase. A phosphatase which catalyzes the release of 32Pi from 32P-labeled phenylalanine hydroxylase has been purified about 50-fold from rat liver extracts. The phosphatase is able to catalyze the removal of only 70 to 80% of the 32Pi leaving about the same amount of Pi still bound to the hydroxylase as was originally present in the native enzyme. Dephosphorylation is accompanied by a corresponding loss in phenylalanine hydroxylase activity when the activity is measured with the natural cofactor, tetrahydrobiopterin, but not when measured with the synthetic cofactor, 6-methyltetrahydropterin. The partially purified phosphatase has very low activity toward p-nitrophenylphosphate, histone phosphate, and phosphorylase a. The activity toward these substrates has not been purified to the same extent as the phenylalanine hydroxylase phosphatase activity."}
{"id": "PMID:199598", "title": "Lactoperoxidase-catalyzed iodination of horse cytochrome c:monoiodotyrosyl 74 cytochrome c.", "content": "Iodination of horse cytochrome c with the lactoperoxidase-hydrogen peroxide-iodide system results initially in the formation of the monoiodotyrosyl 74 derivative. This singly modified protein was obtained in pure form by ion exchange chromatography and preparative column electrophoresis. It shows an intact 695 nm absorption band, the midpoint potential of the native protein, a nuclear magnetic resonance spectrum which indicates an undisturbed heme crevice structure, a normal reaction with antibodies directed against native horse cytochrome c, and circular dichroic spectra in which the only changes from those of the native protein can be ascribed to the spectral properties of iodotyrosine itself. This conformationally intact derivative reacts with the succinate-cytochrome c reductase and the cytochrome c oxidase systems of beef mitochondrial particle preparations indistinguishably from the unmodified protein, showing that the region including tyrosine 74 is not involved in these enzymic electron transfer functions of the protein. The circular dichroic spectra of this derivative indicate that the minima observed at 288 and 282 nm in the spectrum of native ferricytochrome c originate from tyrosyl residue 74.", "contents": "Lactoperoxidase-catalyzed iodination of horse cytochrome c:monoiodotyrosyl 74 cytochrome c. Iodination of horse cytochrome c with the lactoperoxidase-hydrogen peroxide-iodide system results initially in the formation of the monoiodotyrosyl 74 derivative. This singly modified protein was obtained in pure form by ion exchange chromatography and preparative column electrophoresis. It shows an intact 695 nm absorption band, the midpoint potential of the native protein, a nuclear magnetic resonance spectrum which indicates an undisturbed heme crevice structure, a normal reaction with antibodies directed against native horse cytochrome c, and circular dichroic spectra in which the only changes from those of the native protein can be ascribed to the spectral properties of iodotyrosine itself. This conformationally intact derivative reacts with the succinate-cytochrome c reductase and the cytochrome c oxidase systems of beef mitochondrial particle preparations indistinguishably from the unmodified protein, showing that the region including tyrosine 74 is not involved in these enzymic electron transfer functions of the protein. The circular dichroic spectra of this derivative indicate that the minima observed at 288 and 282 nm in the spectrum of native ferricytochrome c originate from tyrosyl residue 74."}
{"id": "PMID:199599", "title": "Nereis cuticle collagen. Isolation and properties of a large fragment resistant to proteolysis by bacterial collagenase.", "content": "Native cuticle collagen, obtained from Nereis virens, was incubated with purified bacterial collagenase (EC 3.4.4.19). The kinetics of proteolysis were monitored by viscometry, in parallel with similar digestions of calf skin collagen. Comparison of the kinetics of digestion of the two collagens, at similar enzyme to substrate ratios (w/w), showed that the native cuticle collagen was relatively refractory to digestion by bacterial collagenase. Characterization of the cuticle collagen digest by sodium dodecyl sulfate-polyacrylamide electrophoresis and agarose gel filtration in CaCl2 showed a large polypeptide, of about 300,000 daltons, to be a major product. The native form of this product, a unique fragment, was isolated from the digest by ethanol precipitation. It was found to have an intrinsic viscosity of 120 dl/g, to have an optical rotary dispersion curve characteristic of collagen, to undergo a typical collagenous thermal transition with a Tm of 23.2 degrees, and to have a calculated molar mass of 900,000 g with molecular dimensions of 9,000 X 13 A. It had an amino acid composition which was similar, but not identical with the native cuticle collagen. Although the original substrate contained two dissimilar chains, A and B, in a molar ratio of 1:2, the collagenase-resistant product appeared to be composed of only one type of polypeptide fragment. Possibly, the original subunits contain similar, if not identical collagenase-resistant regions.", "contents": "Nereis cuticle collagen. Isolation and properties of a large fragment resistant to proteolysis by bacterial collagenase. Native cuticle collagen, obtained from Nereis virens, was incubated with purified bacterial collagenase (EC 3.4.4.19). The kinetics of proteolysis were monitored by viscometry, in parallel with similar digestions of calf skin collagen. Comparison of the kinetics of digestion of the two collagens, at similar enzyme to substrate ratios (w/w), showed that the native cuticle collagen was relatively refractory to digestion by bacterial collagenase. Characterization of the cuticle collagen digest by sodium dodecyl sulfate-polyacrylamide electrophoresis and agarose gel filtration in CaCl2 showed a large polypeptide, of about 300,000 daltons, to be a major product. The native form of this product, a unique fragment, was isolated from the digest by ethanol precipitation. It was found to have an intrinsic viscosity of 120 dl/g, to have an optical rotary dispersion curve characteristic of collagen, to undergo a typical collagenous thermal transition with a Tm of 23.2 degrees, and to have a calculated molar mass of 900,000 g with molecular dimensions of 9,000 X 13 A. It had an amino acid composition which was similar, but not identical with the native cuticle collagen. Although the original substrate contained two dissimilar chains, A and B, in a molar ratio of 1:2, the collagenase-resistant product appeared to be composed of only one type of polypeptide fragment. Possibly, the original subunits contain similar, if not identical collagenase-resistant regions."}
{"id": "PMID:199601", "title": "Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora. VI. Isolation and sequences of eighteen fragments from the cyanogen bromide digest.", "content": "The 1030-residue polypeptide chain of the NAD-specific glutamate dehydrogenase of Neurospora crassa was fragmented by treatment with cyanogen bromide. The isolation and sequences of 18 fragments ranging in size from 4 to 51 residues are described. Some of these peptides proved to be cleavage products resulting from hydrolysis at acid-sensitive aspartyl-prolyl bonds. Some overlaps could be deduced on the basis of known sequences of peptides obtained by tryptic hydrolysis.", "contents": "Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora. VI. Isolation and sequences of eighteen fragments from the cyanogen bromide digest. The 1030-residue polypeptide chain of the NAD-specific glutamate dehydrogenase of Neurospora crassa was fragmented by treatment with cyanogen bromide. The isolation and sequences of 18 fragments ranging in size from 4 to 51 residues are described. Some of these peptides proved to be cleavage products resulting from hydrolysis at acid-sensitive aspartyl-prolyl bonds. Some overlaps could be deduced on the basis of known sequences of peptides obtained by tryptic hydrolysis."}
{"id": "PMID:199602", "title": "Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora. VII. Isolation and sequences of three large cyanogen bromide peptides.", "content": "The isolation and sequences of three peptides of large size from a cyanogen bromide digest of the NAD-specific glutamate dehydrogenase of Neurospora crassa are reported. These three peptides comprise 86, 117, and 134 residues, respectively, and represent approximately 30% of the estimated 1030 residues in the peptide chain.", "contents": "Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora. VII. Isolation and sequences of three large cyanogen bromide peptides. The isolation and sequences of three peptides of large size from a cyanogen bromide digest of the NAD-specific glutamate dehydrogenase of Neurospora crassa are reported. These three peptides comprise 86, 117, and 134 residues, respectively, and represent approximately 30% of the estimated 1030 residues in the peptide chain."}
{"id": "PMID:199603", "title": "Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora. VIII. Isolation and sequences of peptides from a tryptic hydrolysate of the maleylated protein.", "content": "The NAD-specific glutamate dehydrogenase of Neurospora crassa was S-carboxymethylated with [14C]iodoacetate, maleylated, and hydrolyzed with trypsin. The isolation and sequences of the resulting peptides are described. These peptides gave information on the structure of the protein that was previously unknown and gave many overlaps of previously isolated segments of the protein.", "contents": "Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora. VIII. Isolation and sequences of peptides from a tryptic hydrolysate of the maleylated protein. The NAD-specific glutamate dehydrogenase of Neurospora crassa was S-carboxymethylated with [14C]iodoacetate, maleylated, and hydrolyzed with trypsin. The isolation and sequences of the resulting peptides are described. These peptides gave information on the structure of the protein that was previously unknown and gave many overlaps of previously isolated segments of the protein."}
{"id": "PMID:199604", "title": "Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora crassa. IX. Isolation and sequences of several large cyanogen bromide peptides.", "content": "The isolation and sequences of several large peptides from cyanogen bromide cleavage of the 1030-residue polypeptide chain of the NAD-specific glutamate dehydrogenase of Neurospora crassa are described. One of these is in the 669-residue sequence of the COOH-terminal end of the protein. The remaining peptides have been aligned in two partial sequences in the NH2-terminal portion of the polypeptide chain.", "contents": "Nicotinamide adenine dinucleotide-specific glutamate dehydrogenase of Neurospora crassa. IX. Isolation and sequences of several large cyanogen bromide peptides. The isolation and sequences of several large peptides from cyanogen bromide cleavage of the 1030-residue polypeptide chain of the NAD-specific glutamate dehydrogenase of Neurospora crassa are described. One of these is in the 669-residue sequence of the COOH-terminal end of the protein. The remaining peptides have been aligned in two partial sequences in the NH2-terminal portion of the polypeptide chain."}
{"id": "PMID:199607", "title": "Subcellular fractionation and morphology of calf aortic smooth muscle cells. Studies on whole aorta, aortic explants, and subcultures grown under different conditions.", "content": "A comparative biochemical and morphological study was made of calf aortic smooth muscle cells found in situ and grown in vitro under various conditions. Striking alterations in enzyme contents, physical properties, and morphological appearances of lysosomes, endoplasmic reticulum, plasma membranes and, to a lesser extent, mitochondria were observed upon culturing of calf aortic smooth muscle cells. These changes first appeared in cells growing out of tissue explants. They developed further upon subculturing of the cells and depended greatly on the culture conditions used. The alterations included increases in specific activities of some 5- to 25-fold of four acid hydrolases, an average ninefold increase in 5' -nucleotidase, sevenfold increase in cytochrome oxidase, and fourfold increase in neutral alpha-glucosidase in subcultured smooth muscle cells compared to aortic cells in situ. Cell fractionation studies showed significant shifts in the equilibrium densities of plasma membranes, microsomes, and lysosomes, but not of mitochondria, in smooth muscle cells growing out from explants and in subcultured cells, compared to cells isolated from intact aortas. Although the cells grown in vitro exhibited typical phenotypic features of smooth muscle cells such as abundant myofilaments and surface vesicles, alterations in the morphological appearance of the endoplasmic reticulum, Golgi apparatus, and, especially, lysosomes were observed. These results demonstrate significant differences in specific cellular characteristics and functions of aortic smooth muscle cells grown in vitro compared to aortic cells in situ.", "contents": "Subcellular fractionation and morphology of calf aortic smooth muscle cells. Studies on whole aorta, aortic explants, and subcultures grown under different conditions. A comparative biochemical and morphological study was made of calf aortic smooth muscle cells found in situ and grown in vitro under various conditions. Striking alterations in enzyme contents, physical properties, and morphological appearances of lysosomes, endoplasmic reticulum, plasma membranes and, to a lesser extent, mitochondria were observed upon culturing of calf aortic smooth muscle cells. These changes first appeared in cells growing out of tissue explants. They developed further upon subculturing of the cells and depended greatly on the culture conditions used. The alterations included increases in specific activities of some 5- to 25-fold of four acid hydrolases, an average ninefold increase in 5' -nucleotidase, sevenfold increase in cytochrome oxidase, and fourfold increase in neutral alpha-glucosidase in subcultured smooth muscle cells compared to aortic cells in situ. Cell fractionation studies showed significant shifts in the equilibrium densities of plasma membranes, microsomes, and lysosomes, but not of mitochondria, in smooth muscle cells growing out from explants and in subcultured cells, compared to cells isolated from intact aortas. Although the cells grown in vitro exhibited typical phenotypic features of smooth muscle cells such as abundant myofilaments and surface vesicles, alterations in the morphological appearance of the endoplasmic reticulum, Golgi apparatus, and, especially, lysosomes were observed. These results demonstrate significant differences in specific cellular characteristics and functions of aortic smooth muscle cells grown in vitro compared to aortic cells in situ."}
{"id": "PMID:199608", "title": "Macrophage deformability and phagocytosis.", "content": "The influence of several metabolic inhibitors and pharmacologic agents on macrophage deformation (induced by fluid shear stress) was examined in relationship to changes in ATP content and phagocytosis of latex beads. Two relatively specific inhibitors of glycolysis (iodoacetate [IA], and sodium fluoride [NaF]) and a sulfhydryl-binding agent (N-ethylmaleimide [NEM] markedly inhibited phagocytosis and reduced cell deformability. A microtubule-disrupting agent (vinblastine) and a highly specific inhibitor of glycolysis (2-deoxyglucose) markedly inhibited phagocytosis without influencing cell deformability. An organomercurial sulfhydryl binding agent p-chloromercuribenzene (PCMBS) and a microfilament-disrupting agent (cytochalasin B) inhibited phagocytosis and increased cell deformability. The effects of these agents on phagocytosis and cell deformability bore no consistent relationship to alterations in cellular content of ATP. The observation that 2-deoxyglucose, the most specific inhibitor of glycolysis examined, reduced ATP content to levels far lower (15 percent of control values) than those achieved by any other agent examined and inhibited phagocytosis without altering cell deformability, suggests that alterations in cell deformability induced by NaF, IA, NEM, PCMBS, and cytochalasin B are not due to inhibition of glycolysis per se, but instead result from direct or indirect effects of these agents on cell constituents, possibly contractile proteins, which are determinants of cell deformability. The finding that cytochalasin B, NEM, PCMBS, and IA interfere with phagocytosis and alter cell deformability, together with evidence that these agents interact with isolated actin and myosin, suggests that contractile proteins are important both in phagocytosis and as determinants of cell deformability. The observation that vinblastine, colchicines, and heavy water (D(2)O) did not alter cell deformability, even though vinblastine caused formation of intracellular crystals of microtubular protein, indicates that microtubules are not major determinants of cell deformability. The observations that beads adhered normally to surfaces of cytochalasin B- and of PCMBS-treated cells and that shear-stress induced deformation was increased whereas phagocytosis was markedly inhibited, suggest that deformation of cells around beads associated with ingestion depends on some form of cellular (contractile?) activity, whereas deformation of cells by fluid shear stress is a passive phenomenon.", "contents": "Macrophage deformability and phagocytosis. The influence of several metabolic inhibitors and pharmacologic agents on macrophage deformation (induced by fluid shear stress) was examined in relationship to changes in ATP content and phagocytosis of latex beads. Two relatively specific inhibitors of glycolysis (iodoacetate [IA], and sodium fluoride [NaF]) and a sulfhydryl-binding agent (N-ethylmaleimide [NEM] markedly inhibited phagocytosis and reduced cell deformability. A microtubule-disrupting agent (vinblastine) and a highly specific inhibitor of glycolysis (2-deoxyglucose) markedly inhibited phagocytosis without influencing cell deformability. An organomercurial sulfhydryl binding agent p-chloromercuribenzene (PCMBS) and a microfilament-disrupting agent (cytochalasin B) inhibited phagocytosis and increased cell deformability. The effects of these agents on phagocytosis and cell deformability bore no consistent relationship to alterations in cellular content of ATP. The observation that 2-deoxyglucose, the most specific inhibitor of glycolysis examined, reduced ATP content to levels far lower (15 percent of control values) than those achieved by any other agent examined and inhibited phagocytosis without altering cell deformability, suggests that alterations in cell deformability induced by NaF, IA, NEM, PCMBS, and cytochalasin B are not due to inhibition of glycolysis per se, but instead result from direct or indirect effects of these agents on cell constituents, possibly contractile proteins, which are determinants of cell deformability. The finding that cytochalasin B, NEM, PCMBS, and IA interfere with phagocytosis and alter cell deformability, together with evidence that these agents interact with isolated actin and myosin, suggests that contractile proteins are important both in phagocytosis and as determinants of cell deformability. The observation that vinblastine, colchicines, and heavy water (D(2)O) did not alter cell deformability, even though vinblastine caused formation of intracellular crystals of microtubular protein, indicates that microtubules are not major determinants of cell deformability. The observations that beads adhered normally to surfaces of cytochalasin B- and of PCMBS-treated cells and that shear-stress induced deformation was increased whereas phagocytosis was markedly inhibited, suggest that deformation of cells around beads associated with ingestion depends on some form of cellular (contractile?) activity, whereas deformation of cells by fluid shear stress is a passive phenomenon."}
{"id": "PMID:199609", "title": "High-pressure liquid chromatography of amino acids and dipeptides on a tripeptide bonded stationary phase.", "content": "A bonded tripeptide (L-valyl-L-phenylalanyl-L-valine) phase has been used as a stationary phase in liquid chromatography. Unique retention orders and retention variations are shown for phenylthiohydantoin (PTH) derivatives of amino acids and isomeric dipeptides using acidic and basic mobile phases. It is shown that the 25 PTH-amino acids studied here have different capacity ratios when 1% citric acid in water (ca. pH 2.5) is used as the mobile phase. The analysis time for these amino acid derivatives could be shortened without a loss in the resolution by adding 5% methanol to the above mobile phase. Of particular importance is the fact that the basic amino acids are eluted first. Isomeric dipeptides have been resolved by using deionized water (pH 5.5), and 1% sodium citrate in water (pH 7.9), as mobile phases. The data show that the nature of the mobile phases, the pH, and the ionic strength are the important factors affecting the selectivity and efficiency of the separations of amino acids and dipeptides.", "contents": "High-pressure liquid chromatography of amino acids and dipeptides on a tripeptide bonded stationary phase. A bonded tripeptide (L-valyl-L-phenylalanyl-L-valine) phase has been used as a stationary phase in liquid chromatography. Unique retention orders and retention variations are shown for phenylthiohydantoin (PTH) derivatives of amino acids and isomeric dipeptides using acidic and basic mobile phases. It is shown that the 25 PTH-amino acids studied here have different capacity ratios when 1% citric acid in water (ca. pH 2.5) is used as the mobile phase. The analysis time for these amino acid derivatives could be shortened without a loss in the resolution by adding 5% methanol to the above mobile phase. Of particular importance is the fact that the basic amino acids are eluted first. Isomeric dipeptides have been resolved by using deionized water (pH 5.5), and 1% sodium citrate in water (pH 7.9), as mobile phases. The data show that the nature of the mobile phases, the pH, and the ionic strength are the important factors affecting the selectivity and efficiency of the separations of amino acids and dipeptides."}
{"id": "PMID:199610", "title": "Analysis of polybrominated biphenyls.", "content": "High-performance liquid chromatography, gas chromatography-mass spectrometry, ultraviolet spectrometry and nuclear magnetic resonance spectrometry have been used to characterize the behaviour of a number of individual brominated biphenyls and to assess the composition of several mixtures of these compounds. The dependence of retention and spectral characteristics on the bromine content of the substituted biphenyls is discussed and the behaviour of polybrominated biphenyls is compared with that of polychlorinated biphenyls. The applicability of high-performance liquid chromatography to photodegradation studies is demonstrated.", "contents": "Analysis of polybrominated biphenyls. High-performance liquid chromatography, gas chromatography-mass spectrometry, ultraviolet spectrometry and nuclear magnetic resonance spectrometry have been used to characterize the behaviour of a number of individual brominated biphenyls and to assess the composition of several mixtures of these compounds. The dependence of retention and spectral characteristics on the bromine content of the substituted biphenyls is discussed and the behaviour of polybrominated biphenyls is compared with that of polychlorinated biphenyls. The applicability of high-performance liquid chromatography to photodegradation studies is demonstrated."}
{"id": "PMID:199611", "title": "Peptide separations using fluorescence detection.", "content": "The formation of fluorophores by the action of o-phthalaldehyde with amino acids and peptides has provided a highly sensitive assay for these compounds. A relatively simple system for the analysis and separation of peptides, in the range 5 nmole to 10 micromole, normally derived from enzymic digestion of proteins, is described. The system comprises a gradient-generating device feeding volatile pyridine buffers via a pump to a column of cation-exchange resin. Eluate from the column is fed through a proportioning pump to a fluorocolorimeter, output from which is displayed on a recorder. For analytical runs the eluate is mixed with o-phthalaldehyde in borate buffer containing Brij 35 and 2-mercaptoethanol prior to its passage into the detector. For preparative work the eluate stream is split, one reacting with 0-phthalaldehyde, the other for collection. Results on the analysis and preparation of tryptic peptides derived from cytochrome c and Salmonella histidinol dehydrogenase are discussed.", "contents": "Peptide separations using fluorescence detection. The formation of fluorophores by the action of o-phthalaldehyde with amino acids and peptides has provided a highly sensitive assay for these compounds. A relatively simple system for the analysis and separation of peptides, in the range 5 nmole to 10 micromole, normally derived from enzymic digestion of proteins, is described. The system comprises a gradient-generating device feeding volatile pyridine buffers via a pump to a column of cation-exchange resin. Eluate from the column is fed through a proportioning pump to a fluorocolorimeter, output from which is displayed on a recorder. For analytical runs the eluate is mixed with o-phthalaldehyde in borate buffer containing Brij 35 and 2-mercaptoethanol prior to its passage into the detector. For preparative work the eluate stream is split, one reacting with 0-phthalaldehyde, the other for collection. Results on the analysis and preparation of tryptic peptides derived from cytochrome c and Salmonella histidinol dehydrogenase are discussed."}
{"id": "PMID:199613", "title": "Filter paper solid-phase radioimmunoassay for human rotavirus surface immunoglobulins.", "content": "A filter paper solid-phase radioimmunoassay has been developed. Filter paper disks adsorbed a large amount of rotavirus and serum globulin and gave small mean variation of coating and low background binding. The rotavirus isolated from stools from infants with acute enteritis 1, 3, and 4 days after onset of symptoms was shown to be already covered with immunoglobulin G (IgG), IgA, and IgM antibodies by this radioimmunoassay, by immunoelectrophoresis, and by immune electron microscopy. The immunoglobulins covering the virus particle were partially separated during 125I labeling and eluted at the position expected for IgG during Sephadex G-200 gel filtration. Rabbit antiserum prepared against purified fecal rotavirus contained not only rotavirus antibodies but also a fairly large amount of immunoglobulin antibody, reflecting the antibodies on the rotavirus particle surface.", "contents": "Filter paper solid-phase radioimmunoassay for human rotavirus surface immunoglobulins. A filter paper solid-phase radioimmunoassay has been developed. Filter paper disks adsorbed a large amount of rotavirus and serum globulin and gave small mean variation of coating and low background binding. The rotavirus isolated from stools from infants with acute enteritis 1, 3, and 4 days after onset of symptoms was shown to be already covered with immunoglobulin G (IgG), IgA, and IgM antibodies by this radioimmunoassay, by immunoelectrophoresis, and by immune electron microscopy. The immunoglobulins covering the virus particle were partially separated during 125I labeling and eluted at the position expected for IgG during Sephadex G-200 gel filtration. Rabbit antiserum prepared against purified fecal rotavirus contained not only rotavirus antibodies but also a fairly large amount of immunoglobulin antibody, reflecting the antibodies on the rotavirus particle surface."}
{"id": "PMID:199614", "title": "Use of sodium polyanetholesulfonate-CaCl2 for removal of serum nonspecific inhibitors of rubella hemagglutination: comparison with other polyanion-divalent cation combinations.", "content": "By using trypsin-treated human type O cells as indicators, we compared the abilities of four polyanion-divalent cation combinations (heparin-MnCl(2); high-and low-molecular-weight dextran sulfate-CaCl(2); and sodium polyanetholesulfonate [SPS]-CaCl(2)) for removal of serum non-immunoglobulin (lipoprotein) inhibitors of rubella hemagglutination. The combination of SPS-CaCl(2) was found to be the most effective, precipitating completely the pre-beta and beta-lipoproteins and reducing the alpha-lipoprotein levels by more than 50%. Hemagglutination patterns after this treatment were clear and stable, and, when normal sera were tested, hemagglutination-inhibition (HI) titers were comparable to those obtained after standard heparin-MnCl(2) treatment. High-molecular-weight dextran sulfate-CaCl(2) removed serum lipoproteins almost as effectively as SPS-CaCl(2). However, problems of nonspecific agglutination and the heavy hemagglutination patterns resulting made this combination unacceptable for routine purposes. Neither low-molecular-weight dextran sulfate-CaCl(2) nor heparin-MnCl(2) removed the pre-beta lipoproteins completely, and occasionally traces of beta-lipoprotein also remained after treatment. The presence of pre-beta lipoproteins in normal sera after treatment may be of no consequence in the HI test since we have found that the very-low-density lipoprotein fractions obtained by ultracentrifugal methods from normal sera (those corresponding to the pre-beta fractions obtained by electrophoresis) had no HI activity. However, very-low-density lipoprotein fractions from all hyperlipemic sera tested had HI activity (titers ranging from 1:16 to 1:1,024) which, in the majority of cases, was not eliminated after heparin-MnCl(2) treatment. In every case, treatment with SPS-CaCl(2) removed this nonspecific activity completely. Since hyperlipemic sera may occasionally be encountered in routine rubella HI antibody testing, we recommend the use of SPS-CaCl(2) rather than heparin-MnCl(2) for pretreatment of sera.", "contents": "Use of sodium polyanetholesulfonate-CaCl2 for removal of serum nonspecific inhibitors of rubella hemagglutination: comparison with other polyanion-divalent cation combinations. By using trypsin-treated human type O cells as indicators, we compared the abilities of four polyanion-divalent cation combinations (heparin-MnCl(2); high-and low-molecular-weight dextran sulfate-CaCl(2); and sodium polyanetholesulfonate [SPS]-CaCl(2)) for removal of serum non-immunoglobulin (lipoprotein) inhibitors of rubella hemagglutination. The combination of SPS-CaCl(2) was found to be the most effective, precipitating completely the pre-beta and beta-lipoproteins and reducing the alpha-lipoprotein levels by more than 50%. Hemagglutination patterns after this treatment were clear and stable, and, when normal sera were tested, hemagglutination-inhibition (HI) titers were comparable to those obtained after standard heparin-MnCl(2) treatment. High-molecular-weight dextran sulfate-CaCl(2) removed serum lipoproteins almost as effectively as SPS-CaCl(2). However, problems of nonspecific agglutination and the heavy hemagglutination patterns resulting made this combination unacceptable for routine purposes. Neither low-molecular-weight dextran sulfate-CaCl(2) nor heparin-MnCl(2) removed the pre-beta lipoproteins completely, and occasionally traces of beta-lipoprotein also remained after treatment. The presence of pre-beta lipoproteins in normal sera after treatment may be of no consequence in the HI test since we have found that the very-low-density lipoprotein fractions obtained by ultracentrifugal methods from normal sera (those corresponding to the pre-beta fractions obtained by electrophoresis) had no HI activity. However, very-low-density lipoprotein fractions from all hyperlipemic sera tested had HI activity (titers ranging from 1:16 to 1:1,024) which, in the majority of cases, was not eliminated after heparin-MnCl(2) treatment. In every case, treatment with SPS-CaCl(2) removed this nonspecific activity completely. Since hyperlipemic sera may occasionally be encountered in routine rubella HI antibody testing, we recommend the use of SPS-CaCl(2) rather than heparin-MnCl(2) for pretreatment of sera."}
{"id": "PMID:199615", "title": "Vesicular stomatitis virus causes abortion and neonatal death in ferrets.", "content": "Vesicular stomatitis virus caused transplacental infection in ferrets, resulting in infant death. No clinically significant illness was observed in the adult, despite histological changes in the uterus, liver, and spleen.", "contents": "Vesicular stomatitis virus causes abortion and neonatal death in ferrets. Vesicular stomatitis virus caused transplacental infection in ferrets, resulting in infant death. No clinically significant illness was observed in the adult, despite histological changes in the uterus, liver, and spleen."}
{"id": "PMID:199616", "title": "Multiple symmetric lipomatosis: a defect in adrenergic-stimulated lipolysis.", "content": "The cellularity of normal and lipomatous adipose tissue and its response to different lipolytic agents have been studied in a group of 10 patients with multiple symmetric lipomatosis (MSL). In MSL patients, fat cells from lipomatous tissue are smaller than normal, uninvolved adipocytes. Fat cells from lipomata show minimal variations in size following conspicuous increase of lipomatous masses. These findings suggest that the growth of lipomata can be attributed to the neoformation of adipocytes rather than to an enlargement in the single fat cells. The incidence of reduced glucose tolerance and of hyperlipoproteinemia is similar in MSL patients and in controls. A significant reduction in plasma free fatty acids was observed in MSL patients after a 24-h fast as well as after noradrenaline infusion. A specific insensitivity of lipomatous tissue to the lipolytic effect of noradrenaline and isoprenaline was observed in vitro, as indicated by glycerol release in the medium, whereas response to theophylline and to dibutyryl cyclic AMP was retained. The lipolytic response to catecholamines was retained. The lipolytic response to catecholamines was normal in the nonlipomatous adipose tissue of MSL patients. In basal conditions ATP concentrations were similar in normal and in lipomatous adipose tissue. However, incubation with noradrenaline induced a significant fall in intracellular ATP levels in normal tissue, whereas no variations were observed in lipomatous tissue. Theophylline, instead, induced a prompt and significant decrease in intracellular ATP levels in lipomatous tissue. These observations indicate that the block in catecholamine-stimulated lipolysis in lipomatous tissue of MSL patients can be localized at a level preceding the formation of cyclic AMP.", "contents": "Multiple symmetric lipomatosis: a defect in adrenergic-stimulated lipolysis. The cellularity of normal and lipomatous adipose tissue and its response to different lipolytic agents have been studied in a group of 10 patients with multiple symmetric lipomatosis (MSL). In MSL patients, fat cells from lipomatous tissue are smaller than normal, uninvolved adipocytes. Fat cells from lipomata show minimal variations in size following conspicuous increase of lipomatous masses. These findings suggest that the growth of lipomata can be attributed to the neoformation of adipocytes rather than to an enlargement in the single fat cells. The incidence of reduced glucose tolerance and of hyperlipoproteinemia is similar in MSL patients and in controls. A significant reduction in plasma free fatty acids was observed in MSL patients after a 24-h fast as well as after noradrenaline infusion. A specific insensitivity of lipomatous tissue to the lipolytic effect of noradrenaline and isoprenaline was observed in vitro, as indicated by glycerol release in the medium, whereas response to theophylline and to dibutyryl cyclic AMP was retained. The lipolytic response to catecholamines was retained. The lipolytic response to catecholamines was normal in the nonlipomatous adipose tissue of MSL patients. In basal conditions ATP concentrations were similar in normal and in lipomatous adipose tissue. However, incubation with noradrenaline induced a significant fall in intracellular ATP levels in normal tissue, whereas no variations were observed in lipomatous tissue. Theophylline, instead, induced a prompt and significant decrease in intracellular ATP levels in lipomatous tissue. These observations indicate that the block in catecholamine-stimulated lipolysis in lipomatous tissue of MSL patients can be localized at a level preceding the formation of cyclic AMP."}
{"id": "PMID:199617", "title": "Thyroid hormonelike actions of 3,3',5'-L-triiodothyronine nad 3,3'-diiodothyronine.", "content": "l-Thyroxine is converted to 3,5,3'-l-triiodothyronine (T(3)) as well as to 3,3',5'-l-triiodothyronine (reverse T(3)). One product of further deiodination is 3,3'-diiodothyronine (3,3'T(2)). The serum levels of reverse T(3) and 3,3'T(2) change considerably in various physiological and disease states. We previously found that reverse T(3) and 3,3'T(2) bind to the solubilized hepatic nuclear \"receptors\" for thyroid hormones. This led us to study binding and actions of these metabolites in cultured rat pituitary cells in which glucose consumption and growth hormone production are regulated by T(3) and l-thyroxine. Reverse T(3) and 3,3'T(2) stimulated growth hormone production and glucose consumption and inhibited nuclear binding of radioactive T(3). Either metabolite produced maximal effects that equaled those of T(3), and neither inhibited the T(3) response. Further, additive effects were observed when reverse T(3) was combined with submaximal concentrations of T(3). In serum-free and serum-containing media, concentrations of 3,3'T(2) 50- to 70- and 10- to 100-fold greater, respectively, than those of T(3) were required for equivalent stimulations and for inhibition of nuclear binding by T(3). The relative activity differences under the two conditions can be attributed to weaker serum protein binding of 3,3'T(2) than T(3). With cells in serum-free media, reverse T(3) was a less avid competitor than 3,3'T(2) for T(3) binding by the nuclear receptors, and was less potent than 3,3'T(2) (0.001 the potency of T(3)) in inducing growth hormone production or glucose oxidation. In incubations with serum-containing media, reverse T(3) was an ineffective competitor for T(3) binding, and had only 0.1 the inducing potency of 3,3'T(2) (0.001 the potency of T(3)). The weaker activity of reverse T(3) relative to 3,3'T(2) in serum-containing media could be explained by stronger serum binding of reverse T(3) than 3,3'T(2). In addition, after long-term incubation of cells with radioactive reverse T(3), much of the cell-associated radioactivity was recovered as 3,3'T(2). These studies suggest that reverse T(3) and 3,3'T(2) can stimulate thyroid hormone-regulated functions as weak agonists by acting via the same receptors that mediate T(3) actions. Moreover, some of the effects of reverse T(3) may be due to 3,3'T(2) produced by deiodination of reverse T(3).", "contents": "Thyroid hormonelike actions of 3,3',5'-L-triiodothyronine nad 3,3'-diiodothyronine. l-Thyroxine is converted to 3,5,3'-l-triiodothyronine (T(3)) as well as to 3,3',5'-l-triiodothyronine (reverse T(3)). One product of further deiodination is 3,3'-diiodothyronine (3,3'T(2)). The serum levels of reverse T(3) and 3,3'T(2) change considerably in various physiological and disease states. We previously found that reverse T(3) and 3,3'T(2) bind to the solubilized hepatic nuclear \"receptors\" for thyroid hormones. This led us to study binding and actions of these metabolites in cultured rat pituitary cells in which glucose consumption and growth hormone production are regulated by T(3) and l-thyroxine. Reverse T(3) and 3,3'T(2) stimulated growth hormone production and glucose consumption and inhibited nuclear binding of radioactive T(3). Either metabolite produced maximal effects that equaled those of T(3), and neither inhibited the T(3) response. Further, additive effects were observed when reverse T(3) was combined with submaximal concentrations of T(3). In serum-free and serum-containing media, concentrations of 3,3'T(2) 50- to 70- and 10- to 100-fold greater, respectively, than those of T(3) were required for equivalent stimulations and for inhibition of nuclear binding by T(3). The relative activity differences under the two conditions can be attributed to weaker serum protein binding of 3,3'T(2) than T(3). With cells in serum-free media, reverse T(3) was a less avid competitor than 3,3'T(2) for T(3) binding by the nuclear receptors, and was less potent than 3,3'T(2) (0.001 the potency of T(3)) in inducing growth hormone production or glucose oxidation. In incubations with serum-containing media, reverse T(3) was an ineffective competitor for T(3) binding, and had only 0.1 the inducing potency of 3,3'T(2) (0.001 the potency of T(3)). The weaker activity of reverse T(3) relative to 3,3'T(2) in serum-containing media could be explained by stronger serum binding of reverse T(3) than 3,3'T(2). In addition, after long-term incubation of cells with radioactive reverse T(3), much of the cell-associated radioactivity was recovered as 3,3'T(2). These studies suggest that reverse T(3) and 3,3'T(2) can stimulate thyroid hormone-regulated functions as weak agonists by acting via the same receptors that mediate T(3) actions. Moreover, some of the effects of reverse T(3) may be due to 3,3'T(2) produced by deiodination of reverse T(3)."}
{"id": "PMID:199618", "title": "Neurogenic coronary vasoconstrictor effects of digitalis during acute global ischemia in dogs.", "content": "The rapid i.v. administration of digitalis has recently been shown to cause a substantial increase in coronary vascular resistance in the normal heart. This neurogenically mediated decrease in coronary blood flow would be potentially detrimental if it occurred during ischemia. The present study evaluates the effects of i.v. acetylstrophanthidin and digoxin on coronary vascular resistance during acute global ischemia in 29 dogs anesthetized with chloralose and urethane. Under these conditions, 0.5 mg of i.v. acetylstrophanthidin in 15 dogs resulted in erratic increases in coronary vascular resistance. The peak rise was 12+/-5% above control (P less than 0.01). In 7 of the 15 dogs, the initial erratic rise in coronary vascular resistance culminated in a steep rise associated with acute elevation in left ventricular end-diastolic pressure, which in four dogs terminated in ventricular fibrillation. During the nonischemic control periods, the peak rise in coronary vascular resistance with acetylstrophanthidin was 16+/-1% above control (P less than 0.01). In five dogs, prior alpha adrenergic receptor blockade with phenoxybenzamine prevented the rise in coronary vascular resistance with acetylstrophanthidin during ischemia. Similar erratic increases in coronary vascular resistance were observed with i.v. digoxin (1 mg) during ischemia in three dogs. In two of these dogs, there was a progressive rise in coronary vascular resistance associated with elevation of left ventricular end-diastolic pressure and ventricular fibrillation. The increase in coronary vascular resistance with digoxin during ischemia was abolished with phenoxybenzamine in two additional dogs. Thus, i.v. digitalis in the ischemic heart results in potentially detrimental increases in coronary vascular resistance mediated through alpha adrenergic receptor stimulation.", "contents": "Neurogenic coronary vasoconstrictor effects of digitalis during acute global ischemia in dogs. The rapid i.v. administration of digitalis has recently been shown to cause a substantial increase in coronary vascular resistance in the normal heart. This neurogenically mediated decrease in coronary blood flow would be potentially detrimental if it occurred during ischemia. The present study evaluates the effects of i.v. acetylstrophanthidin and digoxin on coronary vascular resistance during acute global ischemia in 29 dogs anesthetized with chloralose and urethane. Under these conditions, 0.5 mg of i.v. acetylstrophanthidin in 15 dogs resulted in erratic increases in coronary vascular resistance. The peak rise was 12+/-5% above control (P less than 0.01). In 7 of the 15 dogs, the initial erratic rise in coronary vascular resistance culminated in a steep rise associated with acute elevation in left ventricular end-diastolic pressure, which in four dogs terminated in ventricular fibrillation. During the nonischemic control periods, the peak rise in coronary vascular resistance with acetylstrophanthidin was 16+/-1% above control (P less than 0.01). In five dogs, prior alpha adrenergic receptor blockade with phenoxybenzamine prevented the rise in coronary vascular resistance with acetylstrophanthidin during ischemia. Similar erratic increases in coronary vascular resistance were observed with i.v. digoxin (1 mg) during ischemia in three dogs. In two of these dogs, there was a progressive rise in coronary vascular resistance associated with elevation of left ventricular end-diastolic pressure and ventricular fibrillation. The increase in coronary vascular resistance with digoxin during ischemia was abolished with phenoxybenzamine in two additional dogs. Thus, i.v. digitalis in the ischemic heart results in potentially detrimental increases in coronary vascular resistance mediated through alpha adrenergic receptor stimulation."}
{"id": "PMID:199619", "title": "H2O2 release from human granulocytes during phagocytosis. Relationship to superoxide anion formation and cellular catabolism of H2O2: studies with normal and cytochalasin B-treated cells.", "content": "Normal and cytochalasin B-treated human granulocytes have been studied to determine some of the interrelationships between phagocytosis-induced respiration and superoxide and hydrogen peroxide formation and release into the extracellular medium by intact cells. By using the scopoletin fluorescent assay to continuously monitor extracellular hydrogen peroxide concentrations during contact of cells with opsonized staphylococci, it was demonstrated that the superoxide scavengers ferricytochrome c and nitroblue tetrazolium significantly reduced the amount of H(2)O(2) released with time from normal cells but did not abolish it. This inhibitory effect was reversed by the simultaneous addition of superoxide dismutase (SOD), whereas the addition of SOD alone increased the amount of detectable H(2)O(2) in the medium. The addition of sodium azide markedly inhibited myeloperoxidase-H(2)O(2)-dependent protein iodination and more than doubled H(2)O(2) release, including the residual amount remaining after exposure of the cells to ferricytochrome c, suggesting its origin from an intracellular pool shared by several pathways for H(2)O(2) catabolism. When cells were pretreated with cytochalasin B and opsonized bacteria added, reduced oxygen consumption was observed, but this was in parallel to a reduction in specific binding of organisms to the cells when compared to normal. Under the influence of inhibited phagosome formation by cytochalasin B, the cells released an increased amount of superoxide and peroxide into the extracellular medium relative to oxygen consumption, and all detectable peroxide release could be inhibited by the addition of ferricytochrome c. Decreased H(2)O(2) production in the presence of this compound could not be ascribed to diminished bacterial binding, decreased oxidase activity, or increased H(2)O(2) catabolism and was reversed by the simultaneous addition of SOD. Furthermore, SOD and ferricytochrome c had similar effects on another H(2)O(2)-dependent reaction, protein iodination, in both normal and cytochalasin B cells. When oxygen consumption, O(2.) (-), and H(2)O(2) release were compared in the presence of azide under identical incubation conditions, the molar relationships for normal cells were 1.00:0.34:0.51 and for cytochalasin B-treated cells 1.00:0.99:0.40, respectively. Nonopsonized, or opsonized but disrupted, bacteria did not stimulate any of these metabolic functions. The results indicate that with normal cells approximately 50% of H(2)O(2) released during phagocytosis is derived directly from O(2.) (-) by dismutation, the remainder appearing from an (intra)cellular source shared by azide-inhibitable heme enzymes. With cytochalasin B treatment the evidence is consistent with the derivation of all H(2)O(2) from an O(2.) (-) precursor which is released from the cell surface. Furthermore, when activated by phagocytic particle binding, the neutrophil O(2.) (-) generating system appears to make more of this compound than can be accounted for by dismutation to H(2)O(2). This establishes conditions for the direct participation of both compounds in the microbicidal and cytocidal activity of these cells.", "contents": "H2O2 release from human granulocytes during phagocytosis. Relationship to superoxide anion formation and cellular catabolism of H2O2: studies with normal and cytochalasin B-treated cells. Normal and cytochalasin B-treated human granulocytes have been studied to determine some of the interrelationships between phagocytosis-induced respiration and superoxide and hydrogen peroxide formation and release into the extracellular medium by intact cells. By using the scopoletin fluorescent assay to continuously monitor extracellular hydrogen peroxide concentrations during contact of cells with opsonized staphylococci, it was demonstrated that the superoxide scavengers ferricytochrome c and nitroblue tetrazolium significantly reduced the amount of H(2)O(2) released with time from normal cells but did not abolish it. This inhibitory effect was reversed by the simultaneous addition of superoxide dismutase (SOD), whereas the addition of SOD alone increased the amount of detectable H(2)O(2) in the medium. The addition of sodium azide markedly inhibited myeloperoxidase-H(2)O(2)-dependent protein iodination and more than doubled H(2)O(2) release, including the residual amount remaining after exposure of the cells to ferricytochrome c, suggesting its origin from an intracellular pool shared by several pathways for H(2)O(2) catabolism. When cells were pretreated with cytochalasin B and opsonized bacteria added, reduced oxygen consumption was observed, but this was in parallel to a reduction in specific binding of organisms to the cells when compared to normal. Under the influence of inhibited phagosome formation by cytochalasin B, the cells released an increased amount of superoxide and peroxide into the extracellular medium relative to oxygen consumption, and all detectable peroxide release could be inhibited by the addition of ferricytochrome c. Decreased H(2)O(2) production in the presence of this compound could not be ascribed to diminished bacterial binding, decreased oxidase activity, or increased H(2)O(2) catabolism and was reversed by the simultaneous addition of SOD. Furthermore, SOD and ferricytochrome c had similar effects on another H(2)O(2)-dependent reaction, protein iodination, in both normal and cytochalasin B cells. When oxygen consumption, O(2.) (-), and H(2)O(2) release were compared in the presence of azide under identical incubation conditions, the molar relationships for normal cells were 1.00:0.34:0.51 and for cytochalasin B-treated cells 1.00:0.99:0.40, respectively. Nonopsonized, or opsonized but disrupted, bacteria did not stimulate any of these metabolic functions. The results indicate that with normal cells approximately 50% of H(2)O(2) released during phagocytosis is derived directly from O(2.) (-) by dismutation, the remainder appearing from an (intra)cellular source shared by azide-inhibitable heme enzymes. With cytochalasin B treatment the evidence is consistent with the derivation of all H(2)O(2) from an O(2.) (-) precursor which is released from the cell surface. Furthermore, when activated by phagocytic particle binding, the neutrophil O(2.) (-) generating system appears to make more of this compound than can be accounted for by dismutation to H(2)O(2). This establishes conditions for the direct participation of both compounds in the microbicidal and cytocidal activity of these cells."}
{"id": "PMID:199620", "title": "Vasopressin-stimulated prostaglandin E biosynthesis in the toad urinary bladder. Effect of water flow.", "content": "Prostaglandin E biosynthesis and its effect on water permeability were investigated in the toad urinary bladder. Arginine vasopressin (1 mU/ml) increased prostaglandin E (PGE) biosynthesis from 0.5+/-0.1 to 5.0+/-0.4 pmol/min per hemibladder (mean +/-SEM, n= 8, P less than 0.001). Maximal vasopressin-stimulated PGE biosynthesis, 6.4+/-0.2 pmol/min per hemibladder, occurred at vasopressin concentrations in excess of 3 mU/ml. Half-maximal stimulation of PGE biosynthesis occurred at a vasopressin concentration of approximately 0.7 mU/ml, whereas half-maximal stimulation of water flow occurred at a vasopressin concentration of approximately 5 mU/ml. Vasopressin-stimulated PGE biosynthesis did not depend on water flow along an osmotic gradient or upon sodium transport. Thin-layer chromatographic analysis of the lipids released from hemibladders labeled with tritium-arachidonic acid revealed that vasopressin stimulates the release of arachidonic acid from intracellular lipid stores without affecting the percentage of free arachidonic acid converted to PGE. Neither cyclic AMP nor theophylline stimulated PGE biosynthesis although they mimic arginine vasopressin (AVP) in stimulating water permeability. Biosynthesis of PGE was inhibited by mepacrine, a phospholipase inhibitor, and by agents that inhibit arachidonic acid oxygenase. The inhibition of PGE biosynthesis resulted in augmented vasopressin- and theophylline-stimulated water flow, but had no effect on cyclic AMP-stimulated water flow. We interpret these results to mean that endogenous PGE inhibits basal and vasopressin-stimulated adenylate cyclase activity. In contrast to the effects of AVP on permeability and transport, AVP stimulates PGE biosynthesis by a mechanism that does not depend on an increase in cellular cyclic AMP levels. The water permeability response of the toad urinary bladder to vasopressin is inhibited by PGE synthesized by the bladder in response to vasopressin.", "contents": "Vasopressin-stimulated prostaglandin E biosynthesis in the toad urinary bladder. Effect of water flow. Prostaglandin E biosynthesis and its effect on water permeability were investigated in the toad urinary bladder. Arginine vasopressin (1 mU/ml) increased prostaglandin E (PGE) biosynthesis from 0.5+/-0.1 to 5.0+/-0.4 pmol/min per hemibladder (mean +/-SEM, n= 8, P less than 0.001). Maximal vasopressin-stimulated PGE biosynthesis, 6.4+/-0.2 pmol/min per hemibladder, occurred at vasopressin concentrations in excess of 3 mU/ml. Half-maximal stimulation of PGE biosynthesis occurred at a vasopressin concentration of approximately 0.7 mU/ml, whereas half-maximal stimulation of water flow occurred at a vasopressin concentration of approximately 5 mU/ml. Vasopressin-stimulated PGE biosynthesis did not depend on water flow along an osmotic gradient or upon sodium transport. Thin-layer chromatographic analysis of the lipids released from hemibladders labeled with tritium-arachidonic acid revealed that vasopressin stimulates the release of arachidonic acid from intracellular lipid stores without affecting the percentage of free arachidonic acid converted to PGE. Neither cyclic AMP nor theophylline stimulated PGE biosynthesis although they mimic arginine vasopressin (AVP) in stimulating water permeability. Biosynthesis of PGE was inhibited by mepacrine, a phospholipase inhibitor, and by agents that inhibit arachidonic acid oxygenase. The inhibition of PGE biosynthesis resulted in augmented vasopressin- and theophylline-stimulated water flow, but had no effect on cyclic AMP-stimulated water flow. We interpret these results to mean that endogenous PGE inhibits basal and vasopressin-stimulated adenylate cyclase activity. In contrast to the effects of AVP on permeability and transport, AVP stimulates PGE biosynthesis by a mechanism that does not depend on an increase in cellular cyclic AMP levels. The water permeability response of the toad urinary bladder to vasopressin is inhibited by PGE synthesized by the bladder in response to vasopressin."}
{"id": "PMID:199621", "title": "Inhibition of vasopressin-stimulated prostaglandin E biosynthesis by chlorpropamide in the toad urinary bladder. Mechanism of enhancement of vasopressin-stimulated water flow.", "content": "Chlorpropamide is known to enhance the water permeability response of the toad urinary bladder to vasopressin and to theophylline. In other studies, we have shown that prostaglandin E synthesis by the toad bladder inhibits the water permeability response to arginine vasopressin and to theophylline. In this study, the effect of chlorpropamide on vasopressin-, theophylline-, and cyclic AMP-stimulated water flow and on prostaglandin E biosynthesis was investigated in the toad urinary bladder in vitro. Chlorpropamide inhibited prostaglandin E biosynthesis during vasopressin-, theophylline- and cyclic AMP-stimulated water flow. Tolbutamide and glyburide, two other sulfonylurea compounds, also enhanced vasopressin-stimulated water flow and inhibited vasopressin-stimulated prostaglandin E biosynthesis. We conclude that the mechanism of enhancement on vasopressin-stimulated water flow by the sulfonylureas is the inhibition of prostaglandin E biosynthesis.", "contents": "Inhibition of vasopressin-stimulated prostaglandin E biosynthesis by chlorpropamide in the toad urinary bladder. Mechanism of enhancement of vasopressin-stimulated water flow. Chlorpropamide is known to enhance the water permeability response of the toad urinary bladder to vasopressin and to theophylline. In other studies, we have shown that prostaglandin E synthesis by the toad bladder inhibits the water permeability response to arginine vasopressin and to theophylline. In this study, the effect of chlorpropamide on vasopressin-, theophylline-, and cyclic AMP-stimulated water flow and on prostaglandin E biosynthesis was investigated in the toad urinary bladder in vitro. Chlorpropamide inhibited prostaglandin E biosynthesis during vasopressin-, theophylline- and cyclic AMP-stimulated water flow. Tolbutamide and glyburide, two other sulfonylurea compounds, also enhanced vasopressin-stimulated water flow and inhibited vasopressin-stimulated prostaglandin E biosynthesis. We conclude that the mechanism of enhancement on vasopressin-stimulated water flow by the sulfonylureas is the inhibition of prostaglandin E biosynthesis."}
{"id": "PMID:199622", "title": "Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport.", "content": "To better understand the pathogenesis of infantile viral gastroenteritis, we studied Na+ and Cl- fluxes in vitro in short-circuited jejunal epithelium from 8-10-day-old piglets after infection with a standard dose of human rotavirus given via nasogastric tube. 11 infected piglets, all of whom became ill, were compared with 9 uninfected, healthy litter-mates. When killed 72 h after infection, intestinal villi were shorter and crypts deeper (P less than 0.025) in duodenum, upper jejunum, and mid-small intestine, but not ileum in infected piglets. Virus antigen was seen by fluorescence microscopy in occasional jejunal villus tip cells in only four infected piglets and no controls at 72 h. Net Na+ and Cl- fluxes did not differ from noninfected litter-mate controls under basal conditions, but response to glucose was blunted in infected piglets (P less than 0.001). Theophylline stimulated net Cl- secretion in both infected and control animals, and cyclic AMP concentration in isolated jejunal villus enterocytes did not differ significantly. In isolated jejunal villus enterocytes of infected piglets, thymidine kinase activity increased (P less than 0.001), and sucrase activity decreased (P less than 0.001). We conclude that in this invasive enteritis caused by a major human viral pathogen, glucose-coupled Na+ transport is impaired in the jejunum at a time when the villus epithelium shows enzyme characteristics of crypt epithelium, and when little or no virus is present. These findings are identical to those occurring in an invasive coronavirus enteritis of piglets but differ markedly from those seen with enterotoxigenic diarrhea.", "contents": "Human rotavirus enteritis induced in conventional piglets. Intestinal structure and transport. To better understand the pathogenesis of infantile viral gastroenteritis, we studied Na+ and Cl- fluxes in vitro in short-circuited jejunal epithelium from 8-10-day-old piglets after infection with a standard dose of human rotavirus given via nasogastric tube. 11 infected piglets, all of whom became ill, were compared with 9 uninfected, healthy litter-mates. When killed 72 h after infection, intestinal villi were shorter and crypts deeper (P less than 0.025) in duodenum, upper jejunum, and mid-small intestine, but not ileum in infected piglets. Virus antigen was seen by fluorescence microscopy in occasional jejunal villus tip cells in only four infected piglets and no controls at 72 h. Net Na+ and Cl- fluxes did not differ from noninfected litter-mate controls under basal conditions, but response to glucose was blunted in infected piglets (P less than 0.001). Theophylline stimulated net Cl- secretion in both infected and control animals, and cyclic AMP concentration in isolated jejunal villus enterocytes did not differ significantly. In isolated jejunal villus enterocytes of infected piglets, thymidine kinase activity increased (P less than 0.001), and sucrase activity decreased (P less than 0.001). We conclude that in this invasive enteritis caused by a major human viral pathogen, glucose-coupled Na+ transport is impaired in the jejunum at a time when the villus epithelium shows enzyme characteristics of crypt epithelium, and when little or no virus is present. These findings are identical to those occurring in an invasive coronavirus enteritis of piglets but differ markedly from those seen with enterotoxigenic diarrhea."}
{"id": "PMID:199623", "title": "An electron microscope observation of the right and the two left portions of the habenular nuclei of the frog.", "content": "The right dorsal habenula (RDH), the left dorsal habenula, lateral portion (LDH-LP) and the left dorsal habenula, medial portion (LDH-MP) of the adult frog Rana esculenta have been studied by the electron microscope with the use of three types of fixatives: osmium tetroxide, aldehydes and potassium permangarate. The study has demonstrated in the habenulae of both sides a variety of syraptic vesicles, special synaptic patterns (en passant, serial, axo-somatic) containing small spherical transparent vesicles, never mixed with other types of vesicles, and large pale processes containing big granules. However, a particular type of synaptic vesicles characterized by small clear spherical vesicles with a tiny dark granule revealed by potassium permanganate fixition has been demonstrated only in the neuropil of the LDH and not in the RDH. Further, a peculiar type of intracytoplasmic inclusion appears in the form of myelin-like and crystal-like formations only in the LDH-MP. On the basis of these consistent ultrastructural differences, the dorsal habenular nuclei of the frog can be considered as composed of three individual nuclei, each with its own morphological characterization, dislocated, for some unknown reason, one on the right and two on the left side of the epithalamus. The results suggest that the LDH-MP is a nucleus metabolically different from the others and that the projections to the dorsal habenular nuclei are different on the right and left sides of the brain.", "contents": "An electron microscope observation of the right and the two left portions of the habenular nuclei of the frog. The right dorsal habenula (RDH), the left dorsal habenula, lateral portion (LDH-LP) and the left dorsal habenula, medial portion (LDH-MP) of the adult frog Rana esculenta have been studied by the electron microscope with the use of three types of fixatives: osmium tetroxide, aldehydes and potassium permangarate. The study has demonstrated in the habenulae of both sides a variety of syraptic vesicles, special synaptic patterns (en passant, serial, axo-somatic) containing small spherical transparent vesicles, never mixed with other types of vesicles, and large pale processes containing big granules. However, a particular type of synaptic vesicles characterized by small clear spherical vesicles with a tiny dark granule revealed by potassium permanganate fixition has been demonstrated only in the neuropil of the LDH and not in the RDH. Further, a peculiar type of intracytoplasmic inclusion appears in the form of myelin-like and crystal-like formations only in the LDH-MP. On the basis of these consistent ultrastructural differences, the dorsal habenular nuclei of the frog can be considered as composed of three individual nuclei, each with its own morphological characterization, dislocated, for some unknown reason, one on the right and two on the left side of the epithalamus. The results suggest that the LDH-MP is a nucleus metabolically different from the others and that the projections to the dorsal habenular nuclei are different on the right and left sides of the brain."}
{"id": "PMID:199624", "title": "Granular cell myoblastoma.", "content": "Electron microscopic observations in three cases of granular cell myoblastoma revealed that this tumor is made up of two types of cells. 1) Granular cells grouped into nests, surrounded by a basement membrane, and displaying characteristic inclusions. Numerous processes were observed close to these cells, showing filamentous and microtubular components lying parallel to their axes. 2) Satellite fibroblasts which included angulated bodies. The relationship between these two types of cells is discussed.", "contents": "Granular cell myoblastoma. Electron microscopic observations in three cases of granular cell myoblastoma revealed that this tumor is made up of two types of cells. 1) Granular cells grouped into nests, surrounded by a basement membrane, and displaying characteristic inclusions. Numerous processes were observed close to these cells, showing filamentous and microtubular components lying parallel to their axes. 2) Satellite fibroblasts which included angulated bodies. The relationship between these two types of cells is discussed."}
{"id": "PMID:199626", "title": "Effects of sodium nitroprusside, nitroglycerin, and sodium azide on levels of cyclic nucleotides and mechanical activity of various tissues.", "content": "Three agents that activate guanylate cyclase, sodium nitroprusside, nitroglycerin and sodium axide, were examined for their effects on cyclic GMP and cyclic AMP accumulation and muscle motility with several tissues. All of these agents, except nitroglycerin with ventricle preparations, increased cyclic GMP levels and did not alter cyclic AMP in incubations of preparations of bovine tracheal smooth muscle, guinea pig tracheal chains, taenia cecum, atria and ventricle, and rat liver and cerebral cortex. Increases in cyclic GMP with these agents occurred with relaxation of smooth muscle preparations and without alteration in the contractility of atrial preparations. These observations support the hypothesis that cyclic GMP accumulation in smooth muscle may be related to relaxation rather than contraction as proposed previously. Relaxation with these agents is not associated with alterations in cyclic AMP levels. Increases in cyclic GMP levels in atrial preparations can also occur without changes in contractile force or rate of contraction.", "contents": "Effects of sodium nitroprusside, nitroglycerin, and sodium azide on levels of cyclic nucleotides and mechanical activity of various tissues. Three agents that activate guanylate cyclase, sodium nitroprusside, nitroglycerin and sodium axide, were examined for their effects on cyclic GMP and cyclic AMP accumulation and muscle motility with several tissues. All of these agents, except nitroglycerin with ventricle preparations, increased cyclic GMP levels and did not alter cyclic AMP in incubations of preparations of bovine tracheal smooth muscle, guinea pig tracheal chains, taenia cecum, atria and ventricle, and rat liver and cerebral cortex. Increases in cyclic GMP with these agents occurred with relaxation of smooth muscle preparations and without alteration in the contractility of atrial preparations. These observations support the hypothesis that cyclic GMP accumulation in smooth muscle may be related to relaxation rather than contraction as proposed previously. Relaxation with these agents is not associated with alterations in cyclic AMP levels. Increases in cyclic GMP levels in atrial preparations can also occur without changes in contractile force or rate of contraction."}
{"id": "PMID:199627", "title": "Distortion of cyclic AMP responses to catecholamine due to destruction of the hormone.", "content": "The acute actions of low and moderate concentrations of catecholamines on cyclic AMP metabolism in SV40-transformed human lung fibroblasts (VA13) were seriously distorted by non-enzymatic destruction of the agonist. Catecholamine destruction, as measured directly with an isotopic method, was slowed by a variety of anti-oxidants and chelating agents. A combination of two anti-oxidants, ascorbate and thiourea, was very effective in protecting isoproterenol in the cell culture system. That is, there was a 10-fold increase in the sensitivity of VA13 to isoproterenol and the duration of action of the catecholamine was greatly prolonged. However, the anti-oxidants did not alter the responses of the cells to prostaglandins. We conclude that any quantitative studies of cyclic AMP responses to catecholamines must address the question of agonist destruction if meaningful results are to be expected. The use of anti-oxidants, especially the combination of ascorbate and thiourea, would appear to be advisable, particularly in situations where the catecholamine concentrations are less than supramaximal.", "contents": "Distortion of cyclic AMP responses to catecholamine due to destruction of the hormone. The acute actions of low and moderate concentrations of catecholamines on cyclic AMP metabolism in SV40-transformed human lung fibroblasts (VA13) were seriously distorted by non-enzymatic destruction of the agonist. Catecholamine destruction, as measured directly with an isotopic method, was slowed by a variety of anti-oxidants and chelating agents. A combination of two anti-oxidants, ascorbate and thiourea, was very effective in protecting isoproterenol in the cell culture system. That is, there was a 10-fold increase in the sensitivity of VA13 to isoproterenol and the duration of action of the catecholamine was greatly prolonged. However, the anti-oxidants did not alter the responses of the cells to prostaglandins. We conclude that any quantitative studies of cyclic AMP responses to catecholamines must address the question of agonist destruction if meaningful results are to be expected. The use of anti-oxidants, especially the combination of ascorbate and thiourea, would appear to be advisable, particularly in situations where the catecholamine concentrations are less than supramaximal."}
{"id": "PMID:199629", "title": "Immunohistochemical localization of cyclic GMP in rat cerebellum.", "content": "The technique of cyclic nucleotide fluorescence immunohistochemistry has been applied for the specific localization of cyclic GMP in rat cerebellum. We report immunofluorescence associated with fibres and membranes, contrasting with previously reported cytoplasmic localization of cyclic AMP in different cell populations, using a similar technique. We have been unable to detect changes in cyclic GMP staining in response to post-mortem changes, harmaline and pentobarbitone administration. A role of cyclic GMP is suggested in membrane ion transport.", "contents": "Immunohistochemical localization of cyclic GMP in rat cerebellum. The technique of cyclic nucleotide fluorescence immunohistochemistry has been applied for the specific localization of cyclic GMP in rat cerebellum. We report immunofluorescence associated with fibres and membranes, contrasting with previously reported cytoplasmic localization of cyclic AMP in different cell populations, using a similar technique. We have been unable to detect changes in cyclic GMP staining in response to post-mortem changes, harmaline and pentobarbitone administration. A role of cyclic GMP is suggested in membrane ion transport."}
{"id": "PMID:199630", "title": "Differences in thermal sensitivities of the regulatory-catalytic and catalytic forms of cyclic AMP-dependent protein kinases from various tissues.", "content": "The cAMP-dependent protein kinase from various tissues was more thermally sensitive when activated by cAMP than the non-activated enzyme. For example, when the activity ratio (the activity of protein kinase assayed -cAMP/+cAMP) was 0.40, 80% and 76% of total hepatic cAMP dependent protein kinase activity was recoverable after incubations at 45 degrees C for 15 and 30 minutes, respectively. However, when the activity ratio was elevated to about 0.80 - 0.90 by increasing cAMP levels in vivo or adding exogenous cAMP to soluble liver extracts, the total protein kinase activity recoverable after incubations at 45 degrees C for 15 minutes was 34-44% and 19-22%, respectively. This observation was used to estimate the degree of activation of the enzyme in vivo and in vitro, since the loss of enzyme activity at 45 degrees C was directly related to the degree of activation of the enzyme in tissue extracts. The regulatory-catalytic form of cAMP-dependent protein kinase was thermally resistant at 45 degrees C unless activated by incubation with exogenous cAMP, histones or NaCl, while the catalytic form of the enzyme was highly thermally sensitive at this same temperature. These data describe a new property of the cAMP-dependent protein kinase and suggest an alternative method which measure the degree of activation of the enzyme.", "contents": "Differences in thermal sensitivities of the regulatory-catalytic and catalytic forms of cyclic AMP-dependent protein kinases from various tissues. The cAMP-dependent protein kinase from various tissues was more thermally sensitive when activated by cAMP than the non-activated enzyme. For example, when the activity ratio (the activity of protein kinase assayed -cAMP/+cAMP) was 0.40, 80% and 76% of total hepatic cAMP dependent protein kinase activity was recoverable after incubations at 45 degrees C for 15 and 30 minutes, respectively. However, when the activity ratio was elevated to about 0.80 - 0.90 by increasing cAMP levels in vivo or adding exogenous cAMP to soluble liver extracts, the total protein kinase activity recoverable after incubations at 45 degrees C for 15 minutes was 34-44% and 19-22%, respectively. This observation was used to estimate the degree of activation of the enzyme in vivo and in vitro, since the loss of enzyme activity at 45 degrees C was directly related to the degree of activation of the enzyme in tissue extracts. The regulatory-catalytic form of cAMP-dependent protein kinase was thermally resistant at 45 degrees C unless activated by incubation with exogenous cAMP, histones or NaCl, while the catalytic form of the enzyme was highly thermally sensitive at this same temperature. These data describe a new property of the cAMP-dependent protein kinase and suggest an alternative method which measure the degree of activation of the enzyme."}
{"id": "PMID:199632", "title": "Effect of exogenous corticotropin and climatic conditions on bovine adrenal cortical function.", "content": "Interactions between three climatic conditions and exogenous adrenocorticotropin (200 IU) or saline on glucocorticoids of plasma were tested in six pregnant Holstein heifers. Animals were under cold (5 C, 30% relative humidity), thermoneutral (18 C, 50% relative humidity), and hot (35 C, and 80% relative humidity) conditions. Effects of treatment, interactions of environment with treatment, and environment with treatment with interval on glucocorticoids of plasma were measured through timed intervals of blood collection at pre- and postintravenous injection of a treatment solution. Adrenocorticotropin elevated corticoid concentrations in plasma, but interactions of environment with treatment and environment by treatment by sampling interval were nil for responses of corticoids in plasma.", "contents": "Effect of exogenous corticotropin and climatic conditions on bovine adrenal cortical function. Interactions between three climatic conditions and exogenous adrenocorticotropin (200 IU) or saline on glucocorticoids of plasma were tested in six pregnant Holstein heifers. Animals were under cold (5 C, 30% relative humidity), thermoneutral (18 C, 50% relative humidity), and hot (35 C, and 80% relative humidity) conditions. Effects of treatment, interactions of environment with treatment, and environment with treatment with interval on glucocorticoids of plasma were measured through timed intervals of blood collection at pre- and postintravenous injection of a treatment solution. Adrenocorticotropin elevated corticoid concentrations in plasma, but interactions of environment with treatment and environment by treatment by sampling interval were nil for responses of corticoids in plasma."}
{"id": "PMID:199633", "title": "Gallium imaging in pediatrics.", "content": "Gallium-67 citrate imaging was carried out in 59 children from 3 mo to 20 yr of age. Indications for the study included the search for occult inflammatory disease and the detection and staging of malignant disease. The Ga-67 citrate scan had a 96% reliability in confirming or excluding the site of purulent material as a cause of sepsis, and 76% reliability in detecting malignant disease. Tissue distributions in children differ from those in adults primarily in that the epiphyseal plates, spleen, and thymus may show increased activity normally and in the presence of sepsis. These variations are illustrated as possible sources of incorrect interpretation. \"Cold\" defects may be seen in sterile collections and avascular masses. Experience in this age group seems sufficiently encouraging to continue the use of gallium-67 citrate for the purposes described.", "contents": "Gallium imaging in pediatrics. Gallium-67 citrate imaging was carried out in 59 children from 3 mo to 20 yr of age. Indications for the study included the search for occult inflammatory disease and the detection and staging of malignant disease. The Ga-67 citrate scan had a 96% reliability in confirming or excluding the site of purulent material as a cause of sepsis, and 76% reliability in detecting malignant disease. Tissue distributions in children differ from those in adults primarily in that the epiphyseal plates, spleen, and thymus may show increased activity normally and in the presence of sepsis. These variations are illustrated as possible sources of incorrect interpretation. \"Cold\" defects may be seen in sterile collections and avascular masses. Experience in this age group seems sufficiently encouraging to continue the use of gallium-67 citrate for the purposes described."}
{"id": "PMID:199634", "title": "A case of myocardial abscess evaluated by radionuclide techniques: case report.", "content": "A patient with infective endocarditis was evaluated by Ga-67 citrate imaging, Tc-99m pyrophosphate imaging, equilibrium gated blood pool imaging, and Tl-201 imaging of the chest. The diagnosis of ventricular abscess was first suggested by an abnormal gallium scan. At surgery, an abscess was identified in the area where the scan was abnormal, and postoperatively a repeat scan was normal.", "contents": "A case of myocardial abscess evaluated by radionuclide techniques: case report. A patient with infective endocarditis was evaluated by Ga-67 citrate imaging, Tc-99m pyrophosphate imaging, equilibrium gated blood pool imaging, and Tl-201 imaging of the chest. The diagnosis of ventricular abscess was first suggested by an abnormal gallium scan. At surgery, an abscess was identified in the area where the scan was abnormal, and postoperatively a repeat scan was normal."}
{"id": "PMID:199635", "title": "Clinical evaluation of the Cleon imager.", "content": "We have compared bone images from a number of patients using three instruments. In 38 patients, Cleon body images were compared with whole-body rectilinear scans. Cleon images were also compared with scintillation camera images of the trunk or extremities of 31 patients and of the skull of 70 patients. The Cleon was superior to the rectilinear scanner in resolution, lesion detectability, and speed of scanning. The Cleon and gamma camera were comparable in lesion detection, but the Cleon was consdierably faster. Clinical studies and comparative evaluation are presented.", "contents": "Clinical evaluation of the Cleon imager. We have compared bone images from a number of patients using three instruments. In 38 patients, Cleon body images were compared with whole-body rectilinear scans. Cleon images were also compared with scintillation camera images of the trunk or extremities of 31 patients and of the skull of 70 patients. The Cleon was superior to the rectilinear scanner in resolution, lesion detectability, and speed of scanning. The Cleon and gamma camera were comparable in lesion detection, but the Cleon was consdierably faster. Clinical studies and comparative evaluation are presented."}
{"id": "PMID:199641", "title": "The calcium and vitamin D status in an elderly female population and their response to administered supplemental vitamin D3.", "content": "Recent reports have implicated the importance of impaired calcium absorption, inadequate dietary vitamin D, and low serum vitamin D levels in the genesis of metabolic bone diseases in the elderly. This study evaluated the dietary intakes of calcium and Vitamin D, calcium absorption, and serum 25 hydroxycholecalciferol (25 OH D) levels in a population of women (mean age 83 yrs) compared to healthy volunteers (mean age 35 yrs). Dietary intakes of both calcium and vitamin D and serum 25 OH D levels were found to be comparable in both groups. Calcium absorption was normal in the subjects studied and did not change significantly after two 2-week periods of oral supplementation with vitamin D3 in doses of 500 I.U./day and 10,000 I.U./day, although the serum 25 OH D levels rose significantly and comparably in both groups. Thus other etiological factors may play relevant roles in the causation of bone diseases in the elderly and unless deficient dietary or serum vitamin D levels are demonstrated, empirical supplementation with vitamin D should not be undertaken. The differences of the above findings from previously published data are discussed.", "contents": "The calcium and vitamin D status in an elderly female population and their response to administered supplemental vitamin D3. Recent reports have implicated the importance of impaired calcium absorption, inadequate dietary vitamin D, and low serum vitamin D levels in the genesis of metabolic bone diseases in the elderly. This study evaluated the dietary intakes of calcium and Vitamin D, calcium absorption, and serum 25 hydroxycholecalciferol (25 OH D) levels in a population of women (mean age 83 yrs) compared to healthy volunteers (mean age 35 yrs). Dietary intakes of both calcium and vitamin D and serum 25 OH D levels were found to be comparable in both groups. Calcium absorption was normal in the subjects studied and did not change significantly after two 2-week periods of oral supplementation with vitamin D3 in doses of 500 I.U./day and 10,000 I.U./day, although the serum 25 OH D levels rose significantly and comparably in both groups. Thus other etiological factors may play relevant roles in the causation of bone diseases in the elderly and unless deficient dietary or serum vitamin D levels are demonstrated, empirical supplementation with vitamin D should not be undertaken. The differences of the above findings from previously published data are discussed."}
{"id": "PMID:199643", "title": "[Indications for hysterectomy in placental tumors].", "content": "Indications for hysterectomy in placental tumours are now most often to carry out hysterectomy as a second attack designed to deal with residual lesions of choriocarcinoma that prove resistant to chemotherapy. Of 80 patients treated, 24 were first seen for chemotherapy after hysterectomy and this is too great a number. On the remaining 56 patients we carried out hysterectomy in 8 cases of whom 7 were secondary to chemotherapy. Seven times we found a residual lesion. These patients are now apparently cured.", "contents": "[Indications for hysterectomy in placental tumors]. Indications for hysterectomy in placental tumours are now most often to carry out hysterectomy as a second attack designed to deal with residual lesions of choriocarcinoma that prove resistant to chemotherapy. Of 80 patients treated, 24 were first seen for chemotherapy after hysterectomy and this is too great a number. On the remaining 56 patients we carried out hysterectomy in 8 cases of whom 7 were secondary to chemotherapy. Seven times we found a residual lesion. These patients are now apparently cured."}
{"id": "PMID:199644", "title": "[Radioimmunoassay of HCG and HCG beta in blood during pregnancy and trophoblastomas].", "content": "This work was carried out on 151 estimations of the radioimmune levels of hCG-hCG beta in the first half of normal pregnancy and 390 levels estimated in 10 molar pregnancies, in 4 choriocarcinomata following moles and 1 primary choriocarcinoma of the ovary using homologous hCG beta. In normal pregnancy the level of hCG-hCG beta rises rapidly. The levels are highest between the 8th and 9th weeks of pregnancy, and then gradually decrease. In active molar pregnancies the levels of hCG-hCG beta in the plasma are significantly higher than those found in normal pregnancies of the same gestational age. When the outcome is going to be favourable the levels drop progressively. Complete absence in peripheral blood is usually found about 14 weeks after a mole has been expelled or evacuated. In choriocarcinomata, if the level of hCG-hCG beta rises it is a certain sign of reactivation of the tumour.", "contents": "[Radioimmunoassay of HCG and HCG beta in blood during pregnancy and trophoblastomas]. This work was carried out on 151 estimations of the radioimmune levels of hCG-hCG beta in the first half of normal pregnancy and 390 levels estimated in 10 molar pregnancies, in 4 choriocarcinomata following moles and 1 primary choriocarcinoma of the ovary using homologous hCG beta. In normal pregnancy the level of hCG-hCG beta rises rapidly. The levels are highest between the 8th and 9th weeks of pregnancy, and then gradually decrease. In active molar pregnancies the levels of hCG-hCG beta in the plasma are significantly higher than those found in normal pregnancies of the same gestational age. When the outcome is going to be favourable the levels drop progressively. Complete absence in peripheral blood is usually found about 14 weeks after a mole has been expelled or evacuated. In choriocarcinomata, if the level of hCG-hCG beta rises it is a certain sign of reactivation of the tumour."}
{"id": "PMID:199666", "title": "Protein A-peroxidase: a valluable tool for the localization of antigens.", "content": "Protein A of Staphylococcus aureus has been conjugated to horseradish peroxidase and used in an indirect immunolabeling technique to visualize membrane and viral antigens. The same Protein A-peroxidase conjugate was used with antisera from five different species. Using this indirect test, membrane markers for T and B lymphocytes were labeled with a greater specificity than when peroxidase conjugated anti-immunoglobulin was used in the second step. Viral antigens on cells infected with measles, vesicular stomatitis, herpes or visna virus, respectively, were also stained in the protein A-peroxidase indirect test with a greater specificity than indirect method using anti-immunoglobulin. Paired preparations were examined in the light and electron microscope. Ultrastructural analysis showed that the protein A-peroxidase conjugate penetrated well through fixed viral membranes and resulted in fine resolution of antigenic sites.", "contents": "Protein A-peroxidase: a valluable tool for the localization of antigens. Protein A of Staphylococcus aureus has been conjugated to horseradish peroxidase and used in an indirect immunolabeling technique to visualize membrane and viral antigens. The same Protein A-peroxidase conjugate was used with antisera from five different species. Using this indirect test, membrane markers for T and B lymphocytes were labeled with a greater specificity than when peroxidase conjugated anti-immunoglobulin was used in the second step. Viral antigens on cells infected with measles, vesicular stomatitis, herpes or visna virus, respectively, were also stained in the protein A-peroxidase indirect test with a greater specificity than indirect method using anti-immunoglobulin. Paired preparations were examined in the light and electron microscope. Ultrastructural analysis showed that the protein A-peroxidase conjugate penetrated well through fixed viral membranes and resulted in fine resolution of antigenic sites."}
{"id": "PMID:199667", "title": "Thymus-derived lymphocyte-dependent rejection of syngeneic papovavirus (SV40) and methylcholanthrene tumors in inbred hamsters.", "content": "Treatment of specifically sensitized MHA hamster lymphoid cells with rabbit antisera specific for hamster thymus-derived lymphocytes, in the presence of C, eliminated those cells capable of inhibiting the growth of syngeneic SV40 and methylcholanthrene tumors in vivo. Thymectomized, lethally-irradiated, bone marrow-reconstituted hamsters, shown to be devoid to T cell function, were, after attempted specific sensitization to the two syngeneic tumor cell lines, unable to reject either tumor by direct challenge in vivo. In addition, lymphocytes from such animals were incapable of inhibiting the growth of either tumor cell line in normal syngeneic recepients in the tumor cell neutralization assay. These data strongly support the conclusion that specifically sensitized thymus-derived lymphocytes are required for the rejection of syngeneic SV40 and methylcholanthrene tumors in inbred hamsters.", "contents": "Thymus-derived lymphocyte-dependent rejection of syngeneic papovavirus (SV40) and methylcholanthrene tumors in inbred hamsters. Treatment of specifically sensitized MHA hamster lymphoid cells with rabbit antisera specific for hamster thymus-derived lymphocytes, in the presence of C, eliminated those cells capable of inhibiting the growth of syngeneic SV40 and methylcholanthrene tumors in vivo. Thymectomized, lethally-irradiated, bone marrow-reconstituted hamsters, shown to be devoid to T cell function, were, after attempted specific sensitization to the two syngeneic tumor cell lines, unable to reject either tumor by direct challenge in vivo. In addition, lymphocytes from such animals were incapable of inhibiting the growth of either tumor cell line in normal syngeneic recepients in the tumor cell neutralization assay. These data strongly support the conclusion that specifically sensitized thymus-derived lymphocytes are required for the rejection of syngeneic SV40 and methylcholanthrene tumors in inbred hamsters."}
{"id": "PMID:199669", "title": "Modulation of Fc-mediated phagocytosis by cyclic AMP and insulin in a macrophage-like cell line.", "content": "Studies on genetically selected mutants in phagocytosis of E[IgG] indicated that the defect in some mutants could be corrected by addition of 8 Br-cAMP, and suggested that cyclic AMP may be involved in the mechanism of phagocytosis through the Fc receptor. In order to elucidate the role of cyclic AMP in phagocytosis in the parental, nonmutant macrophage-like cell line, J774.2, it was necessary to employ restrictive conditions which rendered phagocytosis suboptimal. When 4774.2 cells were cultured in nontissue culture Petri dishes phagocytosis was markedly reduced. Addition of 8 Br-cAMP or inducers of intracellular cyclic AMP such as isoproterenol restored the phagocytic ability of these cells. Similarly, treatment of the parental J774.2 cells with insulin reduced the level of phagocytosis, and once again this suppression could be corrected by addition of 8 Br-cAMP. In no case did AMP mimic the effects of 8 Br-cAMP. The effect of cyclic AMP action in this system was not instantaneous, but rather reached optimal levels at 5 to 10 hr, suggesting that cyclic AMP is not the immediate signal for phagocytosis. The genetic analysis of macrophage variants may provide a useful model for studies on the mechanisms of phagocytosis, and also the effects of insulin and cyclic AMP on an easily measurable biologic function in a specialized cell type.", "contents": "Modulation of Fc-mediated phagocytosis by cyclic AMP and insulin in a macrophage-like cell line. Studies on genetically selected mutants in phagocytosis of E[IgG] indicated that the defect in some mutants could be corrected by addition of 8 Br-cAMP, and suggested that cyclic AMP may be involved in the mechanism of phagocytosis through the Fc receptor. In order to elucidate the role of cyclic AMP in phagocytosis in the parental, nonmutant macrophage-like cell line, J774.2, it was necessary to employ restrictive conditions which rendered phagocytosis suboptimal. When 4774.2 cells were cultured in nontissue culture Petri dishes phagocytosis was markedly reduced. Addition of 8 Br-cAMP or inducers of intracellular cyclic AMP such as isoproterenol restored the phagocytic ability of these cells. Similarly, treatment of the parental J774.2 cells with insulin reduced the level of phagocytosis, and once again this suppression could be corrected by addition of 8 Br-cAMP. In no case did AMP mimic the effects of 8 Br-cAMP. The effect of cyclic AMP action in this system was not instantaneous, but rather reached optimal levels at 5 to 10 hr, suggesting that cyclic AMP is not the immediate signal for phagocytosis. The genetic analysis of macrophage variants may provide a useful model for studies on the mechanisms of phagocytosis, and also the effects of insulin and cyclic AMP on an easily measurable biologic function in a specialized cell type."}
{"id": "PMID:199673", "title": "Resistance of Bordetella pertussis phase I to mucociliary clearance by rabbit tracheal mucous membrane.", "content": "Cultivated mucous membrane of rabbit trachea was point inoculated with Bordetella pertussis phase I or III. Phase I (virulent) bacteria were found to be infective at the point-inoculated site, but phase III (avirulent) bacteria rarely showed such behavior. After inoculation, homogenized segments of mucous membrane were spread on plates. Large numbers of phase I bacteria were recovered from the inoculated segment; however, the laryngeal segment was the site of recovery of large numbers of phase III bacteria. The difference was not due to the ciliostatic bacterial toxin. After coinoculation with phase I and III bacteria, phase III bacteria were recognized at the laryngeal end, whereas phase I bacteria were recognized at the inoculated site. Therefore, the adherence of the bacteria to the ciliated epithelium is considered to be the most probable mechanism of the resistance to the mucociliary stream. Scanning electron microscopy facilitated visualization of phase I bacteria adhering to the inoculated site.", "contents": "Resistance of Bordetella pertussis phase I to mucociliary clearance by rabbit tracheal mucous membrane. Cultivated mucous membrane of rabbit trachea was point inoculated with Bordetella pertussis phase I or III. Phase I (virulent) bacteria were found to be infective at the point-inoculated site, but phase III (avirulent) bacteria rarely showed such behavior. After inoculation, homogenized segments of mucous membrane were spread on plates. Large numbers of phase I bacteria were recovered from the inoculated segment; however, the laryngeal segment was the site of recovery of large numbers of phase III bacteria. The difference was not due to the ciliostatic bacterial toxin. After coinoculation with phase I and III bacteria, phase III bacteria were recognized at the laryngeal end, whereas phase I bacteria were recognized at the inoculated site. Therefore, the adherence of the bacteria to the ciliated epithelium is considered to be the most probable mechanism of the resistance to the mucociliary stream. Scanning electron microscopy facilitated visualization of phase I bacteria adhering to the inoculated site."}
{"id": "PMID:199674", "title": "Regional localization of activity of Clostridium perfringens type A enterotoxin in the rabbit ileum, jejunum, and duodenum.", "content": "Rabbit ileal, jejunal, and duodenal loops were exposed to purified enterotoxin from Clostridium perfringens type A and then perfused for comparative analysis of effects of the enterotoxin on each region of the intestine. Ileal loops responded with enhanced net secretion of fluid and sodium, inhibition of chloride and glucose uptake, and substantial sloughing of epithelial cells. The jejunum responded with fluid secretion, enhancement of sodium secretion only during the first 20 min, inhibition of chloride and glucose uptake, and substantial sloughing of epithelial cells. In the duodenum, transport of fluid, sodium, and chloride was significantly altered only during the first 20 min of perfusion, and significant inhibition of glucose uptake varied from one period to another. Epithelial damage was much less than that seen in the jejunum or ileum. Levels of fluid protein in all three sections corresponded closely to extent of tissue damage. In general, it was found that the severity of response to fixed doses of enterotoxin varied as follows: ileum greater than jejunum greater than duodenum.", "contents": "Regional localization of activity of Clostridium perfringens type A enterotoxin in the rabbit ileum, jejunum, and duodenum. Rabbit ileal, jejunal, and duodenal loops were exposed to purified enterotoxin from Clostridium perfringens type A and then perfused for comparative analysis of effects of the enterotoxin on each region of the intestine. Ileal loops responded with enhanced net secretion of fluid and sodium, inhibition of chloride and glucose uptake, and substantial sloughing of epithelial cells. The jejunum responded with fluid secretion, enhancement of sodium secretion only during the first 20 min, inhibition of chloride and glucose uptake, and substantial sloughing of epithelial cells. In the duodenum, transport of fluid, sodium, and chloride was significantly altered only during the first 20 min of perfusion, and significant inhibition of glucose uptake varied from one period to another. Epithelial damage was much less than that seen in the jejunum or ileum. Levels of fluid protein in all three sections corresponded closely to extent of tissue damage. In general, it was found that the severity of response to fixed doses of enterotoxin varied as follows: ileum greater than jejunum greater than duodenum."}
{"id": "PMID:199675", "title": "Interaction of cytomegalovirus with leukocytes from patients with mononucleosis due to cytomegalovirus.", "content": "Cytomegalovirus (CMV) was isolated from hemic cells from seven of seven patients with acute CMV mononucleosis and from one of six patients with mononucleosis during convalescence. CMV was isolated from the mononuclear leukocyte fraction, the polymorphonuclear leukocyte fraction, or both cell fractions. Virus was not detected in washed erythrocytes, plasma, or leukocyte lysates. Mononuclear leukocytes from patients with acute CMV mononucleosis displayed an elevated level of incorporation of [3H]thymidine on the day of donation compared with that in cells from convalescent patients or normal donors. Responses to pokeweed mitogen and concanavalin A were significantly lower in patients with CMV mononucleosis than in normal donors. There were no significant differences among the acute, convalescent, and normal donor groups in response to phytohemagglutinin or in the one-way mixed leukocyte reaction. These findings suggest that in patients with CMV mononucleosis virus infects and may persist within peripheral blood leukocytes and that the lymphocytes of these patients are selectively hyporesponsive to certain mitogens.", "contents": "Interaction of cytomegalovirus with leukocytes from patients with mononucleosis due to cytomegalovirus. Cytomegalovirus (CMV) was isolated from hemic cells from seven of seven patients with acute CMV mononucleosis and from one of six patients with mononucleosis during convalescence. CMV was isolated from the mononuclear leukocyte fraction, the polymorphonuclear leukocyte fraction, or both cell fractions. Virus was not detected in washed erythrocytes, plasma, or leukocyte lysates. Mononuclear leukocytes from patients with acute CMV mononucleosis displayed an elevated level of incorporation of [3H]thymidine on the day of donation compared with that in cells from convalescent patients or normal donors. Responses to pokeweed mitogen and concanavalin A were significantly lower in patients with CMV mononucleosis than in normal donors. There were no significant differences among the acute, convalescent, and normal donor groups in response to phytohemagglutinin or in the one-way mixed leukocyte reaction. These findings suggest that in patients with CMV mononucleosis virus infects and may persist within peripheral blood leukocytes and that the lymphocytes of these patients are selectively hyporesponsive to certain mitogens."}
{"id": "PMID:199676", "title": "Herpetic whitlow as part of genital virus infection.", "content": "Lesions on fingers or hands caused by Herpesvirus hominis have in the past been attributed to inoculation with virus-containing oropharyngeal secretions. Often these \"herpetic whitlows\" were caused by H. hominis type 1 and occurred in medical personnel. A recent series of 13 recurrent \"herpetic whitlows\" yielded 11 isolates of H. hominis type 2 and only two of H. hominis type 1. None of the subjects was engaged in patient care, and none had oral or facial herpetic lesions. Nine of the 11 infections due to H. hominis type 2 were in females, and more than half were associated with genital herpetic lesions. Herpetic finger or hand lesions in adults appear to be a common part of genital virus infections caused by H. hominis type 2 and are not associated with infections acquired in hospitals or during primary gingivostomatitis.", "contents": "Herpetic whitlow as part of genital virus infection. Lesions on fingers or hands caused by Herpesvirus hominis have in the past been attributed to inoculation with virus-containing oropharyngeal secretions. Often these \"herpetic whitlows\" were caused by H. hominis type 1 and occurred in medical personnel. A recent series of 13 recurrent \"herpetic whitlows\" yielded 11 isolates of H. hominis type 2 and only two of H. hominis type 1. None of the subjects was engaged in patient care, and none had oral or facial herpetic lesions. Nine of the 11 infections due to H. hominis type 2 were in females, and more than half were associated with genital herpetic lesions. Herpetic finger or hand lesions in adults appear to be a common part of genital virus infections caused by H. hominis type 2 and are not associated with infections acquired in hospitals or during primary gingivostomatitis."}
{"id": "PMID:199680", "title": "Clinical and histological malignancy of adenoid cystic carcinoma.", "content": "The authors report on 25 cases of adenoid cystic carcinoma of the head and neck region. The tumours were divided into 4 histological malignancy groups. Treatment generally consisted of surgery performed with as large a margin as possible, in combination with split course million volt therapy, about 6,000 rads, usually given preoperatively. It was found that the patients in the groups of lower malignancy generally managed for a comparatively long time without a clinically demonstrable recurrence, while the patients in the groups of higher malignancy relapsed rather quickly and often had metastases. The patients in the groups of higher malignancy also died relatively soon after the histological tumour preparations.", "contents": "Clinical and histological malignancy of adenoid cystic carcinoma. The authors report on 25 cases of adenoid cystic carcinoma of the head and neck region. The tumours were divided into 4 histological malignancy groups. Treatment generally consisted of surgery performed with as large a margin as possible, in combination with split course million volt therapy, about 6,000 rads, usually given preoperatively. It was found that the patients in the groups of lower malignancy generally managed for a comparatively long time without a clinically demonstrable recurrence, while the patients in the groups of higher malignancy relapsed rather quickly and often had metastases. The patients in the groups of higher malignancy also died relatively soon after the histological tumour preparations."}
{"id": "PMID:199681", "title": "Cryptophthalmos: symptoms and treatment of a rare deformity. A case report.", "content": "Since 1872 more than 50 cases of the cryptophthalmos syndrome have been reported. In addition to other deformities, the typical anomalies of this syndrome are the missing palpebral fissure, eyebrow and the rudimentary eyeball. This paper deals with the possibilities of operative correction in a 13-year-old female. We are of the opinion that by means of plastic surgery, social integration into the community of the patient is possible.", "contents": "Cryptophthalmos: symptoms and treatment of a rare deformity. A case report. Since 1872 more than 50 cases of the cryptophthalmos syndrome have been reported. In addition to other deformities, the typical anomalies of this syndrome are the missing palpebral fissure, eyebrow and the rudimentary eyeball. This paper deals with the possibilities of operative correction in a 13-year-old female. We are of the opinion that by means of plastic surgery, social integration into the community of the patient is possible."}
{"id": "PMID:199684", "title": "[Metabolism and action of intracellular magnesium (author's transl)].", "content": "The activity of Mg2+-activated enzymes shows a bell shaped pMg dependency, with a pMg optimum at 3. Intracellular Mg2+ concentrations, determined by different methods, are about 10(-3) mol/1. Thus Mg2+-dependent enzymes are optimally activated, or nearly so, with Mg2+. If the substrates of an enzyme form complexes with Mg2+ of different stabilities, and if free substrate and the substrate-Mg2+ complex react differently with the enzyme, the equilibrium will change with the concentration of Mg2+. When the extracellular concentration of Mg2+ is increased, Mg2+ becomes bound practically exclusively to the cell membrane. In Mg2+ deficiency, the intracellular concentrations of Na+, K+, Ca2+ and cycl. AMP are changed, and the rates of synthesis of DNA, RNA and protein are decreased.", "contents": "[Metabolism and action of intracellular magnesium (author's transl)]. The activity of Mg2+-activated enzymes shows a bell shaped pMg dependency, with a pMg optimum at 3. Intracellular Mg2+ concentrations, determined by different methods, are about 10(-3) mol/1. Thus Mg2+-dependent enzymes are optimally activated, or nearly so, with Mg2+. If the substrates of an enzyme form complexes with Mg2+ of different stabilities, and if free substrate and the substrate-Mg2+ complex react differently with the enzyme, the equilibrium will change with the concentration of Mg2+. When the extracellular concentration of Mg2+ is increased, Mg2+ becomes bound practically exclusively to the cell membrane. In Mg2+ deficiency, the intracellular concentrations of Na+, K+, Ca2+ and cycl. AMP are changed, and the rates of synthesis of DNA, RNA and protein are decreased."}
{"id": "PMID:199688", "title": "Cation and anion sequences in dark-adapted Balanus photoreceptor.", "content": "Anion and cation permeabilities in dark-adapted Balanus photoreceptors were determined by comparing changes in the membrane potential in response to replacement of the dominant anion (Cl-) or cation (Na+) by test anions or cations in the superfusing solution. The anion permeability sequence obtained was PI greater than PSO4 greater than PBr greater than PCl greater than Pisethionate greater than Pmethanesulfonate. Gluconate, glucuronate, and glutamate generally appeared more permeable and propionate less permeable than Cl-. The alkali-metal cation permeability sequence obtained was PK greater than PRb greater than PCx greater than PNa approximately PLi. This corresponds to Eisenman's IV which is the same sequencethat has been obtained for other classes of nerve cells in the resting state. The values obtained for the permeability ratios of the alkali-metal cations are considered to be minimal. The membrane conductance measured by passing inward current pulses in the different test cations followed the sequence, GK greater than GRb greater than GCs greater than GNa greater than GLi. The conductance ratios obtained for a full substitution of the test cation agreed quite well with permeability ratios for all the alkali-metal cations except K+ which was generally higher.", "contents": "Cation and anion sequences in dark-adapted Balanus photoreceptor. Anion and cation permeabilities in dark-adapted Balanus photoreceptors were determined by comparing changes in the membrane potential in response to replacement of the dominant anion (Cl-) or cation (Na+) by test anions or cations in the superfusing solution. The anion permeability sequence obtained was PI greater than PSO4 greater than PBr greater than PCl greater than Pisethionate greater than Pmethanesulfonate. Gluconate, glucuronate, and glutamate generally appeared more permeable and propionate less permeable than Cl-. The alkali-metal cation permeability sequence obtained was PK greater than PRb greater than PCx greater than PNa approximately PLi. This corresponds to Eisenman's IV which is the same sequencethat has been obtained for other classes of nerve cells in the resting state. The values obtained for the permeability ratios of the alkali-metal cations are considered to be minimal. The membrane conductance measured by passing inward current pulses in the different test cations followed the sequence, GK greater than GRb greater than GCs greater than GNa greater than GLi. The conductance ratios obtained for a full substitution of the test cation agreed quite well with permeability ratios for all the alkali-metal cations except K+ which was generally higher."}
{"id": "PMID:199690", "title": "Replication of enterovirus 70 in non-primate cell cultures.", "content": "Replication of the strain J 670/71 of enterovirus 70 (EV70) in non-primate cell cultures at 33 degrees C was studied using strain L (mouse), BHK21 (hamster), RK13 (rabbit), RK17 (rabbit), PK15 (porcine), IB-RS-2 (porcine), ESK (porcine), MDBK (bovine), and BK1 (primary bovine) together with that of the LSc, 2ab strain of poliovrus type 1 (PV1) as a control. All the cells tested adsorbed from 54 to 90% of EV70. The replication with complete c.p.e. was evident in RK13, RK17 and BK1 cells; replication without c.p.e. was shown in L, BHK21, IB-RS-2 and ESK; but PK15 and MDBK were non-permissive despite a high virus adsorption rate. On the contrary, none of these non-primate cells allowed the adsorption and growth of PV1. One-step growth of EV70 in RK13 was almost identical with that in the primate cells. Two other strains of EV70 were found having similar host range in vitro. Therefore, it is concluded that EV70 has a wider host range in vitro than ordinary human enteroviruses, and its implication is discussed.", "contents": "Replication of enterovirus 70 in non-primate cell cultures. Replication of the strain J 670/71 of enterovirus 70 (EV70) in non-primate cell cultures at 33 degrees C was studied using strain L (mouse), BHK21 (hamster), RK13 (rabbit), RK17 (rabbit), PK15 (porcine), IB-RS-2 (porcine), ESK (porcine), MDBK (bovine), and BK1 (primary bovine) together with that of the LSc, 2ab strain of poliovrus type 1 (PV1) as a control. All the cells tested adsorbed from 54 to 90% of EV70. The replication with complete c.p.e. was evident in RK13, RK17 and BK1 cells; replication without c.p.e. was shown in L, BHK21, IB-RS-2 and ESK; but PK15 and MDBK were non-permissive despite a high virus adsorption rate. On the contrary, none of these non-primate cells allowed the adsorption and growth of PV1. One-step growth of EV70 in RK13 was almost identical with that in the primate cells. Two other strains of EV70 were found having similar host range in vitro. Therefore, it is concluded that EV70 has a wider host range in vitro than ordinary human enteroviruses, and its implication is discussed."}
{"id": "PMID:199691", "title": "The effect of temperature on the synthesis of rhinovirus type 2 RNA.", "content": "The reduced yields of rhinovirus type 2 at temperatures above 37 degrees C were shown to result from the degradation of virus-induced RNA, leaving little RNA available for inclusion into mature infectious virions. The degradation occurred about 6 h p.i., and appeared to be selectively effecting the single-stranded species. Lysosomal nucleases do not appear to have a role in this supra-optimal degradation.", "contents": "The effect of temperature on the synthesis of rhinovirus type 2 RNA. The reduced yields of rhinovirus type 2 at temperatures above 37 degrees C were shown to result from the degradation of virus-induced RNA, leaving little RNA available for inclusion into mature infectious virions. The degradation occurred about 6 h p.i., and appeared to be selectively effecting the single-stranded species. Lysosomal nucleases do not appear to have a role in this supra-optimal degradation."}
{"id": "PMID:199693", "title": "Growth of cytomegalovirus at supra-optimal temperatures.", "content": "An isolate (Mira) of cytomegalovirus is shown to replicate in human embryonic lung fibroblasts at supra-optimal temperature (40 degrees C). The ability of the Mira isolate to grow at 40 degrees C decreased as a function of age of cells in which the virus was grown. The unusual morphology of the lesions in late passage cells infected and maintained at 40 degrees C is illustrated.", "contents": "Growth of cytomegalovirus at supra-optimal temperatures. An isolate (Mira) of cytomegalovirus is shown to replicate in human embryonic lung fibroblasts at supra-optimal temperature (40 degrees C). The ability of the Mira isolate to grow at 40 degrees C decreased as a function of age of cells in which the virus was grown. The unusual morphology of the lesions in late passage cells infected and maintained at 40 degrees C is illustrated."}
{"id": "PMID:199695", "title": "Some properties of recombinants between type 1 and type 2 herpes simplex viruses.", "content": "Four intertypic recombinants of herpes simplex virus have been shown to possess genetic information for functions characteristic of each of the two parental types. The functions were identified by (a) polyacrylamide gel electrophoresis of purified virus particles and of polypeptides synthesized in cells infected with the recombinants and (b) analysis of antigenic sites interacting with type specific neutralizing antibody. The analysis shows that each recombinant possess a different combination of these type specific markers. Finally we have been unable to detect recombination between herpes simplex type 1 and pseudorabies viruses.", "contents": "Some properties of recombinants between type 1 and type 2 herpes simplex viruses. Four intertypic recombinants of herpes simplex virus have been shown to possess genetic information for functions characteristic of each of the two parental types. The functions were identified by (a) polyacrylamide gel electrophoresis of purified virus particles and of polypeptides synthesized in cells infected with the recombinants and (b) analysis of antigenic sites interacting with type specific neutralizing antibody. The analysis shows that each recombinant possess a different combination of these type specific markers. Finally we have been unable to detect recombination between herpes simplex type 1 and pseudorabies viruses."}
{"id": "PMID:199696", "title": "Studies on the structure of a coronavirus-avian infectious bronchitis virus.", "content": "When avian infectious bronchitis virus (IBV) is fixed in formaldehyde, negative stain is able to penetrate the particle and an internal component is visualized. This component is seen as a tongue or flask shaped structure attached at one point to the outer virus membrane. A model yielding transmission patterns similar to the virus has been made. Gradient centrifugation studies on IBV reveal that the RNP is associated with the internal sac.", "contents": "Studies on the structure of a coronavirus-avian infectious bronchitis virus. When avian infectious bronchitis virus (IBV) is fixed in formaldehyde, negative stain is able to penetrate the particle and an internal component is visualized. This component is seen as a tongue or flask shaped structure attached at one point to the outer virus membrane. A model yielding transmission patterns similar to the virus has been made. Gradient centrifugation studies on IBV reveal that the RNP is associated with the internal sac."}
{"id": "PMID:199697", "title": "Biological properties of avian coronavirus RNA.", "content": "RNA with a sedimentation coefficient of 64S was isolated from infectious bronchitis virus, an avian coronavirus. The SNA contained a polyadenylic acid tract and was found to be infectious.", "contents": "Biological properties of avian coronavirus RNA. RNA with a sedimentation coefficient of 64S was isolated from infectious bronchitis virus, an avian coronavirus. The SNA contained a polyadenylic acid tract and was found to be infectious."}
{"id": "PMID:199698", "title": "The circular, segmented nucleocapsid of an arenavirus-Tacaribe virus.", "content": "The nucleocapsid structures of Tacaribe virus, a member of the Arenaviridae, were purified from detergent-treated virus particles by equilibrium density gradient centrifugation. Negative-contrast electron microscopy indicated that they were coiled, circular filaments. They had a mean diam. of 5 to 10 nm and two predominant length classes of 640 nm and 1300 nm were found.", "contents": "The circular, segmented nucleocapsid of an arenavirus-Tacaribe virus. The nucleocapsid structures of Tacaribe virus, a member of the Arenaviridae, were purified from detergent-treated virus particles by equilibrium density gradient centrifugation. Negative-contrast electron microscopy indicated that they were coiled, circular filaments. They had a mean diam. of 5 to 10 nm and two predominant length classes of 640 nm and 1300 nm were found."}
{"id": "PMID:199699", "title": "Infectious DNA from cells infected with feline syncytium-forming virus (Spumavirinae).", "content": "DNA isolated from cells infected with FSFV (a foamy virus) is infectious when tested on susceptible cells. The virus produced by this infectious DNA is identical to the original infecting virus in terms of plaque and virion morphology and serology.", "contents": "Infectious DNA from cells infected with feline syncytium-forming virus (Spumavirinae). DNA isolated from cells infected with FSFV (a foamy virus) is infectious when tested on susceptible cells. The virus produced by this infectious DNA is identical to the original infecting virus in terms of plaque and virion morphology and serology."}
{"id": "PMID:199700", "title": "Resistance to murine cytomegalovirus linked to the major histocompatibility complex of the mouse.", "content": "Studies of the resistance patterns to infection with a murine cytomegalovirus in inbred strains of mice revealed the existence of resistant and susceptible strains. Resistance was found to be associated with possession of the H-2k allele at the major histocompatibility locus of the mouse. The F1 hybrid between a resistant strain (C3H/HeJ) and a susceptible strain (BALB/c) was found to have a resistance intermediate between that of both parents, indicating that the gene(s) controlling resistance is partly dominant. Susceptible BALB/c mice could be made resistant to lethal infection by pre-treatment with thioglycollate broth but not by pre-treatment with endotoxin or BCG. Resistant C3H/HeJ mice could be made susceptible to lethal infection by pre-treatment with cyclophosphamide.", "contents": "Resistance to murine cytomegalovirus linked to the major histocompatibility complex of the mouse. Studies of the resistance patterns to infection with a murine cytomegalovirus in inbred strains of mice revealed the existence of resistant and susceptible strains. Resistance was found to be associated with possession of the H-2k allele at the major histocompatibility locus of the mouse. The F1 hybrid between a resistant strain (C3H/HeJ) and a susceptible strain (BALB/c) was found to have a resistance intermediate between that of both parents, indicating that the gene(s) controlling resistance is partly dominant. Susceptible BALB/c mice could be made resistant to lethal infection by pre-treatment with thioglycollate broth but not by pre-treatment with endotoxin or BCG. Resistant C3H/HeJ mice could be made susceptible to lethal infection by pre-treatment with cyclophosphamide."}
{"id": "PMID:199701", "title": "Localization of the restrictive event of EMC virus replication in semi-permissive monkey and monkey-mouse hybrid cells.", "content": "Encephalomyocarditis (EMC) virus replication was investigated in permissive mouse MKS cells, semi-permissive monkey CV1 cells, and in somatic monkey-mouse MKCVIII hybrid cells whose permissiveness is under the negative control of the simian genome. We found that in CV1 cells the synthesis of both single- and double-stranded virus RNAs was restricted. In contrast, in semi-permissive hybrid Cl4/3 cells only the single-stranded virus RNA was synthesized in small amounts, whereas the double-stranded virus RNA accumulated late after infection. The synthesis of virus polyribosomes and virus polypeptides was lowered in semipermissive conditions. In the presence of quaternary ammonium ions, the synthesis of EMC virus was partially relieved in CV1 cells. Thus, it can be postulated that a defective function in the replication complex is involved in the restrictive event.", "contents": "Localization of the restrictive event of EMC virus replication in semi-permissive monkey and monkey-mouse hybrid cells. Encephalomyocarditis (EMC) virus replication was investigated in permissive mouse MKS cells, semi-permissive monkey CV1 cells, and in somatic monkey-mouse MKCVIII hybrid cells whose permissiveness is under the negative control of the simian genome. We found that in CV1 cells the synthesis of both single- and double-stranded virus RNAs was restricted. In contrast, in semi-permissive hybrid Cl4/3 cells only the single-stranded virus RNA was synthesized in small amounts, whereas the double-stranded virus RNA accumulated late after infection. The synthesis of virus polyribosomes and virus polypeptides was lowered in semipermissive conditions. In the presence of quaternary ammonium ions, the synthesis of EMC virus was partially relieved in CV1 cells. Thus, it can be postulated that a defective function in the replication complex is involved in the restrictive event."}
{"id": "PMID:199702", "title": "Separation and infectivity of two particle types of human rotavirus.", "content": "Two morphological types of human rotavirus particles were separated in caesium chloride density gradients. The particles of higher density ('incomplete' particles without an outer capsid layer) banded at a density of 1-38 g/ml, while the less dense ('complete' particles with an outer as well as an inner capsid layer) banded at a density of 1-36 g/ml. Some particles were found with an incomplete outer layer of capsomeres. The particle/infectivity ratio for tissue cultures of the fraction containing complete particles was more than 3 log10 higher than that of the fraction containing incomplete particles. But, as there was a small number of complete particles in the fraction containing mostly incomplete particles, it was impossible to determine whether the incomplete particles had a low infectivity or whether they had none at all.", "contents": "Separation and infectivity of two particle types of human rotavirus. Two morphological types of human rotavirus particles were separated in caesium chloride density gradients. The particles of higher density ('incomplete' particles without an outer capsid layer) banded at a density of 1-38 g/ml, while the less dense ('complete' particles with an outer as well as an inner capsid layer) banded at a density of 1-36 g/ml. Some particles were found with an incomplete outer layer of capsomeres. The particle/infectivity ratio for tissue cultures of the fraction containing complete particles was more than 3 log10 higher than that of the fraction containing incomplete particles. But, as there was a small number of complete particles in the fraction containing mostly incomplete particles, it was impossible to determine whether the incomplete particles had a low infectivity or whether they had none at all."}
{"id": "PMID:199703", "title": "Effects of cycloheximide and puromycin on the antiviral and anticellular activities of human interferon.", "content": "Human leucocyte interferon has antiviral activity and anticellular effects on the transformed human cell lines, RSa and RSb. Treatment of the cells with cycloheximide or puromycin at 0-5 to 5-0 microgram/ml suppressed the antiviral action of interferon but increased its anticellular effects. Interferon also has antiviral activity in IFr cells, but this is relatively resistant to its anticellular action. Nevertheless, both drugs suppressed the antiviral activity of interferon and increased its anticellular action.", "contents": "Effects of cycloheximide and puromycin on the antiviral and anticellular activities of human interferon. Human leucocyte interferon has antiviral activity and anticellular effects on the transformed human cell lines, RSa and RSb. Treatment of the cells with cycloheximide or puromycin at 0-5 to 5-0 microgram/ml suppressed the antiviral action of interferon but increased its anticellular effects. Interferon also has antiviral activity in IFr cells, but this is relatively resistant to its anticellular action. Nevertheless, both drugs suppressed the antiviral activity of interferon and increased its anticellular action."}
{"id": "PMID:199704", "title": "Induction of interferon in human lymphoblastoid cells by Sendai and measles viruses.", "content": "Sendai and measles viruses were tested for their interferon-induced capacity in human lymphoblast cells. Sendai virus reproducibly induced considerable amounts of interferon (I research reference interferon unit/10(3) cells), but no increase in infectious virus titre was observed. Two Edmonston-Enders strains of measles virus grew very well. The attenuated (A) strain was a good interferon inducer (4 units/10(3) cells), while the virulent (V) strain induced only minimal amounts at a high multiplicity of infection. Pre-treatment of the cells with 5-iododeoxyuridine (IdUrd) had no effect on the growth of Sendai or EE measles virus and on interferon yields induced by Sendai virus. It slightly potentiated interferon induction by EE measles virus. Partial u.v.-light-inactivation of Sendai virus infectivity resulted in a parallel loss in interferon-inducing capacity.", "contents": "Induction of interferon in human lymphoblastoid cells by Sendai and measles viruses. Sendai and measles viruses were tested for their interferon-induced capacity in human lymphoblast cells. Sendai virus reproducibly induced considerable amounts of interferon (I research reference interferon unit/10(3) cells), but no increase in infectious virus titre was observed. Two Edmonston-Enders strains of measles virus grew very well. The attenuated (A) strain was a good interferon inducer (4 units/10(3) cells), while the virulent (V) strain induced only minimal amounts at a high multiplicity of infection. Pre-treatment of the cells with 5-iododeoxyuridine (IdUrd) had no effect on the growth of Sendai or EE measles virus and on interferon yields induced by Sendai virus. It slightly potentiated interferon induction by EE measles virus. Partial u.v.-light-inactivation of Sendai virus infectivity resulted in a parallel loss in interferon-inducing capacity."}
{"id": "PMID:199705", "title": "Circular and circular-linear DNA molecules of herpes simplex virus.", "content": "Circular and circular-linear DNA molecules of herpes simplex virus were isolated from infected cells. Two types of circular-linear DNA molecules are described, one with a circular component of about 8 micrometer and a linear component of 45 micrometer and the other with a circular component of 45 micrometer and a linear component of 8 micrometer. The circular DNA molecules were either the size of linear DNA molecules or were shorter and corresponded to the length of the L (long) component of linear virus DNA.", "contents": "Circular and circular-linear DNA molecules of herpes simplex virus. Circular and circular-linear DNA molecules of herpes simplex virus were isolated from infected cells. Two types of circular-linear DNA molecules are described, one with a circular component of about 8 micrometer and a linear component of 45 micrometer and the other with a circular component of 45 micrometer and a linear component of 8 micrometer. The circular DNA molecules were either the size of linear DNA molecules or were shorter and corresponded to the length of the L (long) component of linear virus DNA."}
{"id": "PMID:199706", "title": "Cell DNA replication as a function in the synthesis of human cytomegalovirus.", "content": "The rate of virus and cell DNA synthesis was studied in human embryonic lung cells pre-treated with 5-iodo-2'-deoxyuridine (IdUrd) and exposed to cytomegalovirus (CMV) or medium. Analysis of DNA in CMV-infected cells following sequential 4 h pulses with 3H-thymidine indicated that a temporal relationship existed in the pattern of virus and cell DNA synthesis. The pattern of DNA replication in infected cells resembled that of a typical cell cycle, whereas the rate of cell DNA synthesis in uninfected cells remained low throughout the study. Increased rates of cell and virus DNA synthesis began concomitantly at 16 h post-infection and reached a maximum at 36 h post-infection. The rate of DNA synthesis then declined and remained at lower levels until 48 h post-infection. This was subsequently followed by a second increase in the rate of cell and virus DNA synthesis. The rates of cell and virus DNA replication were similar throughout the study in that increased and decreased rates of synthesis occurred simultaneously. It was of interest to note that CMV induced cell DNA replication in IDUrd arrested cells; in contrast, addition of fresh serum did not induce a similar increase in the rate of DNA synthesis in IdUrd arrested, but uninfected, cells.", "contents": "Cell DNA replication as a function in the synthesis of human cytomegalovirus. The rate of virus and cell DNA synthesis was studied in human embryonic lung cells pre-treated with 5-iodo-2'-deoxyuridine (IdUrd) and exposed to cytomegalovirus (CMV) or medium. Analysis of DNA in CMV-infected cells following sequential 4 h pulses with 3H-thymidine indicated that a temporal relationship existed in the pattern of virus and cell DNA synthesis. The pattern of DNA replication in infected cells resembled that of a typical cell cycle, whereas the rate of cell DNA synthesis in uninfected cells remained low throughout the study. Increased rates of cell and virus DNA synthesis began concomitantly at 16 h post-infection and reached a maximum at 36 h post-infection. The rate of DNA synthesis then declined and remained at lower levels until 48 h post-infection. This was subsequently followed by a second increase in the rate of cell and virus DNA synthesis. The rates of cell and virus DNA replication were similar throughout the study in that increased and decreased rates of synthesis occurred simultaneously. It was of interest to note that CMV induced cell DNA replication in IDUrd arrested cells; in contrast, addition of fresh serum did not induce a similar increase in the rate of DNA synthesis in IdUrd arrested, but uninfected, cells."}
{"id": "PMID:199707", "title": "Phophorylation of polyoma and SV40 virus proteins.", "content": "The polypeptides of polyoma and SV40 virions are phosphorylated. An estimate of the amount of phosphorylation of the major virus capsid protein (VPI) has been made using two-dimensional gel electrophoresis to resolve phosphorylated from non-phosphorylated forms. The results suggest that in both polyoma and SV40 virions about 12% of VPI molecules are phosphorylated. In unassembled VPI molecules immunoprecipitated from extracts of infected cells the proportion is greater, about 33%. The possibility that phosphorylated VPI may form the penton proteins of the virus capsid is discussed.", "contents": "Phophorylation of polyoma and SV40 virus proteins. The polypeptides of polyoma and SV40 virions are phosphorylated. An estimate of the amount of phosphorylation of the major virus capsid protein (VPI) has been made using two-dimensional gel electrophoresis to resolve phosphorylated from non-phosphorylated forms. The results suggest that in both polyoma and SV40 virions about 12% of VPI molecules are phosphorylated. In unassembled VPI molecules immunoprecipitated from extracts of infected cells the proportion is greater, about 33%. The possibility that phosphorylated VPI may form the penton proteins of the virus capsid is discussed."}
{"id": "PMID:199708", "title": "Sarcoid-like disorder of the intracranial optic nerve.", "content": "Two cases with a sarcoid-like disorder apparently restricted to the intracranial optic nerve and the adjacent dura mater are described, doublilng the number of reported cases. In both instances there were unilateral visual loss and unusual radiographic changes in the optic canal area. Biopsy samples showed localised infiltration of tissues with non-caseating tubercles containing epithelioid and multinucleated giant cells.", "contents": "Sarcoid-like disorder of the intracranial optic nerve. Two cases with a sarcoid-like disorder apparently restricted to the intracranial optic nerve and the adjacent dura mater are described, doublilng the number of reported cases. In both instances there were unilateral visual loss and unusual radiographic changes in the optic canal area. Biopsy samples showed localised infiltration of tissues with non-caseating tubercles containing epithelioid and multinucleated giant cells."}
{"id": "PMID:199709", "title": "Sleep apnoea syndrome: states of sleep and autonomic dysfunction.", "content": "Eleven patients with upper airway apnoea during sleep (one with SHY-Drager syndrome) were monitored polygraphically for wakefulness, sleep, and cardiovascular variables. Systemic hypertension and most of the severe arrhythmias recorded during sleep were secondary to repetitive obstructive apnonea and were mediated through the autonomic nervous system. Sleep related elevations of pulmonary arterial pressure were not influenced by atropine or impaired autonomic functions. Upper airway sleep apnoea is sleep related; the type of sleep (REM or NREM) is critical in the appearance of abnormalities. The distinction between two patient subgroups (total sleep dependent and NREM sleep dependent) has haemodynamic, and possibly long-term, implications. Sleep apnoea syndrome should be looked for in pateints with the Shy-Drager syndrome.", "contents": "Sleep apnoea syndrome: states of sleep and autonomic dysfunction. Eleven patients with upper airway apnoea during sleep (one with SHY-Drager syndrome) were monitored polygraphically for wakefulness, sleep, and cardiovascular variables. Systemic hypertension and most of the severe arrhythmias recorded during sleep were secondary to repetitive obstructive apnonea and were mediated through the autonomic nervous system. Sleep related elevations of pulmonary arterial pressure were not influenced by atropine or impaired autonomic functions. Upper airway sleep apnoea is sleep related; the type of sleep (REM or NREM) is critical in the appearance of abnormalities. The distinction between two patient subgroups (total sleep dependent and NREM sleep dependent) has haemodynamic, and possibly long-term, implications. Sleep apnoea syndrome should be looked for in pateints with the Shy-Drager syndrome."}
{"id": "PMID:199710", "title": "Immunofluorescence studies in a case of rheumatoid neuropathy.", "content": "Findings in a sural nerve biopsy from a patient with rheumatoid neuropathy are reported. Inflammatory changes in different stages were observed in epineurial arterioles. Arterioles with fibrinoid necrosis contained IgG, IgM, rheumatoid factor and complement. The same substances were found at the inner site of the perineurial sheaths. It is suggested that these proteins leaked out of endoneurial vessels and became trapped in the perineurial sheaths. With anti-herpes simplex virus serum fluorescence was seen in monuclear cells of infiltrated vessel walls. This virus could not be isolated in tissue culture.", "contents": "Immunofluorescence studies in a case of rheumatoid neuropathy. Findings in a sural nerve biopsy from a patient with rheumatoid neuropathy are reported. Inflammatory changes in different stages were observed in epineurial arterioles. Arterioles with fibrinoid necrosis contained IgG, IgM, rheumatoid factor and complement. The same substances were found at the inner site of the perineurial sheaths. It is suggested that these proteins leaked out of endoneurial vessels and became trapped in the perineurial sheaths. With anti-herpes simplex virus serum fluorescence was seen in monuclear cells of infiltrated vessel walls. This virus could not be isolated in tissue culture."}
{"id": "PMID:199711", "title": "Respective importance of different electrophysiological parameters in alcoholic neuropathy.", "content": "An electrophysiological study of alcoholic and normal subjects is presented. The aim was to evaluate the respective importance of the various parameters. The subjects were divided into 4 groups: (I) normal subjects; (II) chronic alcoholics without clinical evidence of neuropathy; (III) chronic alcoholics with sensory symptoms; (IV) chronic alcoholics with both motor and sensory symptoms. The electrophysiological parameters tested were: conduction velocity (CV) in Ia sensory fibres, motor fibres, and cutaneous sensory fibres of the popliteal nerve, CV in the sural nerve, amplitude of the cutaneous sensory action potentials (SAP) in the sural and popliteal nerves, H reflex and M response of the soleus muscle, and electromyograms from the extensor digitorum brevis muscle. In the 3 groups of alcoholics, the electrophysiological findings were more abnormal than the clinical symptoms could have predicted. The more sensitive parameters were: (1) CV in the Ia sensory fibres of the popliteal nerve, which is slowed very early (in Group II) and (2) measurement of the amplitude of sural and popliteal SAP's which are also reduced early (in Group II). The nature of the mechanisms involved are discussed.", "contents": "Respective importance of different electrophysiological parameters in alcoholic neuropathy. An electrophysiological study of alcoholic and normal subjects is presented. The aim was to evaluate the respective importance of the various parameters. The subjects were divided into 4 groups: (I) normal subjects; (II) chronic alcoholics without clinical evidence of neuropathy; (III) chronic alcoholics with sensory symptoms; (IV) chronic alcoholics with both motor and sensory symptoms. The electrophysiological parameters tested were: conduction velocity (CV) in Ia sensory fibres, motor fibres, and cutaneous sensory fibres of the popliteal nerve, CV in the sural nerve, amplitude of the cutaneous sensory action potentials (SAP) in the sural and popliteal nerves, H reflex and M response of the soleus muscle, and electromyograms from the extensor digitorum brevis muscle. In the 3 groups of alcoholics, the electrophysiological findings were more abnormal than the clinical symptoms could have predicted. The more sensitive parameters were: (1) CV in the Ia sensory fibres of the popliteal nerve, which is slowed very early (in Group II) and (2) measurement of the amplitude of sural and popliteal SAP's which are also reduced early (in Group II). The nature of the mechanisms involved are discussed."}
{"id": "PMID:199712", "title": "Electron-microscopic appearance of the DA virus, a demyelinating murine virus.", "content": "The DA virus is a neurotropic murine virus which can induce acute encephalomyelitis in suckling mice and a chronic myelopathy in weanlings. The agent has been attenuated by serial passage in baby hamster kidney (BHK-21) cells. When attenuated virus is inoculated in 8-week-old C3HeJ mice a myelopathy of delayed onset with prominent demyelination of lateral and anterior columns occurs. The DA virus is believed to be related to the Theiler murine encephalomyelitis (TME) viruses because of the similar clinical and pathological conditions which it causes, and because neutralization tests indicate shared antigens between it and GD7, a TME virus. This paper reports electron-microscopic studies of BHK-21 cells infected with DA virus. The cells were prepared 24 and 48 hr after inoculation. Cytopathic effects were observed and infected cells contained plaques consisting of numerous 25 nm virus particles in crystalline array. The virions were exclusively intracytoplasmic and were morphologically indistinguishable from human poliomyelitis virus. These observations appear to establish DA as a picorna virus, related to the TME virus group. The chronic myelopathy caused by DA may prove relevant to chronic demyelinative myelopathies in man, such as multiple sclerosis, and also to amyotrophic lateral sclerosis.", "contents": "Electron-microscopic appearance of the DA virus, a demyelinating murine virus. The DA virus is a neurotropic murine virus which can induce acute encephalomyelitis in suckling mice and a chronic myelopathy in weanlings. The agent has been attenuated by serial passage in baby hamster kidney (BHK-21) cells. When attenuated virus is inoculated in 8-week-old C3HeJ mice a myelopathy of delayed onset with prominent demyelination of lateral and anterior columns occurs. The DA virus is believed to be related to the Theiler murine encephalomyelitis (TME) viruses because of the similar clinical and pathological conditions which it causes, and because neutralization tests indicate shared antigens between it and GD7, a TME virus. This paper reports electron-microscopic studies of BHK-21 cells infected with DA virus. The cells were prepared 24 and 48 hr after inoculation. Cytopathic effects were observed and infected cells contained plaques consisting of numerous 25 nm virus particles in crystalline array. The virions were exclusively intracytoplasmic and were morphologically indistinguishable from human poliomyelitis virus. These observations appear to establish DA as a picorna virus, related to the TME virus group. The chronic myelopathy caused by DA may prove relevant to chronic demyelinative myelopathies in man, such as multiple sclerosis, and also to amyotrophic lateral sclerosis."}
{"id": "PMID:199713", "title": "Myotonic dystrophy with nerve hypertrophy. Report of a case with electrophysiological and ultrastructural study of the sural nerve.", "content": "A striking enlargement of peripheral nerves was observed in a patient with myotonic dystrophy (Steinert's disease). Clinical findings disclosed a polyneuropathy which was confirmed by electrophysiological and morphological investigations. Myopathic as well as neurogenic alterations were found on electromyography in wasted hand muscles. The prominent finding on ultrastructural study of sural nerve biopsy was an important collagen infiltration with rather few \"onior bulb\" formations. This extensive endoneural collagen formation appeared to be responsible for the nerve hypertrophy. Evidence of segmental demyelination and remyelination was also found. Glycogen deposits were present in some myelinated axons and is some Schwann cells. Peculiar crystalline inclusions were observed in fibroblasts processes. The relation between myotonic dystrophy and polyneuropathy remains a matter of discussion.", "contents": "Myotonic dystrophy with nerve hypertrophy. Report of a case with electrophysiological and ultrastructural study of the sural nerve. A striking enlargement of peripheral nerves was observed in a patient with myotonic dystrophy (Steinert's disease). Clinical findings disclosed a polyneuropathy which was confirmed by electrophysiological and morphological investigations. Myopathic as well as neurogenic alterations were found on electromyography in wasted hand muscles. The prominent finding on ultrastructural study of sural nerve biopsy was an important collagen infiltration with rather few \"onior bulb\" formations. This extensive endoneural collagen formation appeared to be responsible for the nerve hypertrophy. Evidence of segmental demyelination and remyelination was also found. Glycogen deposits were present in some myelinated axons and is some Schwann cells. Peculiar crystalline inclusions were observed in fibroblasts processes. The relation between myotonic dystrophy and polyneuropathy remains a matter of discussion."}
{"id": "PMID:199714", "title": "Vitamin E binding proteins in human serum.", "content": "The distribution of vitamin E in human serum lipoprotein fraction was investigated by measuring the amount of vitamin E in various protein fractions prepared by ultracentrifugation, gel filtration and electrophoresis. The larger part of the total serum vitamin E (up to 44%) was present in the alpha1-lipoproteins, while the beta-lipoproteins contained smaller concentrations (up to 26%).", "contents": "Vitamin E binding proteins in human serum. The distribution of vitamin E in human serum lipoprotein fraction was investigated by measuring the amount of vitamin E in various protein fractions prepared by ultracentrifugation, gel filtration and electrophoresis. The larger part of the total serum vitamin E (up to 44%) was present in the alpha1-lipoproteins, while the beta-lipoproteins contained smaller concentrations (up to 26%)."}
{"id": "PMID:199715", "title": "Application of 13C-NMR spectroscopy to in vitro analysis of enzyme kinetics.", "content": "The conversion of D,L-alpha-13C-histidine to similarly labeled alpha-13C histamine by bacterial and mammalian histidine decarboxylase was studied by 13C-NMR spectroscopy and GLC-mass spectrometry. The results obtained with the partially purified bacterial enzyme were in essentially perfect agreement with results obtained simultaneously with a standard  radioisotopic  method using carboxyl-labeled-14C-L-histidine. For a crude tissue preparation of the mammalian enzyme, the radioisotopic method indicated an activity three times that based on 13C-NMR measurement of alpha-13C-histamine. The difference in results was accountable in terms of additional 13C-NMR signals attributable to  products other than histamine due in part to enzymatic degradation of the latter.", "contents": "Application of 13C-NMR spectroscopy to in vitro analysis of enzyme kinetics. The conversion of D,L-alpha-13C-histidine to similarly labeled alpha-13C histamine by bacterial and mammalian histidine decarboxylase was studied by 13C-NMR spectroscopy and GLC-mass spectrometry. The results obtained with the partially purified bacterial enzyme were in essentially perfect agreement with results obtained simultaneously with a standard  radioisotopic  method using carboxyl-labeled-14C-L-histidine. For a crude tissue preparation of the mammalian enzyme, the radioisotopic method indicated an activity three times that based on 13C-NMR measurement of alpha-13C-histamine. The difference in results was accountable in terms of additional 13C-NMR signals attributable to  products other than histamine due in part to enzymatic degradation of the latter."}
{"id": "PMID:199719", "title": "A role for endogneous prostaglandins in the short-circuit current responses to osmolal changes in isolated frog skin.", "content": "1. Reduction in osmolality of the Ringer solution bathing the morphological inside of frog skin (by lowering the NaCl concentration) caused a significant increase in sodium transport as measured by the short-circuit current. Pretreatment of the skin with acetylsalicylic acid (2.5 x 10(-4)M) abolished the short-circuit current and open-circuit potential responses to osmolal change.2. The output of prostaglandin-like material from isolated frog skin was increased by incubating the skin in hypotonic Ringer solution.3. The cyclic AMP levels of isolated frog skin were also increased by a reduction in the osmolality of the Ringer fluid bathing the skin.4. Prostaglandin-like material was released both by the separated epithelial and dermal layers of frog skin and the output from both layers, on a unit wet weight basis, did not differ.5. The output of prostaglandin-like material from the separated layers of the skin was substantially greater than from whole skin. Indomethacin (6 x 10(-6)M) reduced the output of this material by more than 90% from both layers.6. The release of prostaglandin-like material from the separated layers of the skin was not altered by a reduction in osmolality of the bathing medium.7. It is concluded that a reduction in the osmolality of the solution bathing frog skin stimulates prostaglandin production and that the increased level of prostaglandins stimulates transepithelial sodium transport by stimulating cyclic AMP accumulation. It is also concluded that the response to osmolal change can only occur in intact skin since separation of the epithelial and dermal layers abolished the increase in the release of prostaglandin-like material to osmolal change. The site of the increased prostaglandin production and the exact nature of the stimulus remain to be determined.", "contents": "A role for endogneous prostaglandins in the short-circuit current responses to osmolal changes in isolated frog skin. 1. Reduction in osmolality of the Ringer solution bathing the morphological inside of frog skin (by lowering the NaCl concentration) caused a significant increase in sodium transport as measured by the short-circuit current. Pretreatment of the skin with acetylsalicylic acid (2.5 x 10(-4)M) abolished the short-circuit current and open-circuit potential responses to osmolal change.2. The output of prostaglandin-like material from isolated frog skin was increased by incubating the skin in hypotonic Ringer solution.3. The cyclic AMP levels of isolated frog skin were also increased by a reduction in the osmolality of the Ringer fluid bathing the skin.4. Prostaglandin-like material was released both by the separated epithelial and dermal layers of frog skin and the output from both layers, on a unit wet weight basis, did not differ.5. The output of prostaglandin-like material from the separated layers of the skin was substantially greater than from whole skin. Indomethacin (6 x 10(-6)M) reduced the output of this material by more than 90% from both layers.6. The release of prostaglandin-like material from the separated layers of the skin was not altered by a reduction in osmolality of the bathing medium.7. It is concluded that a reduction in the osmolality of the solution bathing frog skin stimulates prostaglandin production and that the increased level of prostaglandins stimulates transepithelial sodium transport by stimulating cyclic AMP accumulation. It is also concluded that the response to osmolal change can only occur in intact skin since separation of the epithelial and dermal layers abolished the increase in the release of prostaglandin-like material to osmolal change. The site of the increased prostaglandin production and the exact nature of the stimulus remain to be determined."}
{"id": "PMID:199721", "title": "[A study on the gustatory effects of tetrodotoxin in rat (author's transl)].", "content": "Effects of tetrodotoxin (TTX) on neural responses of the chorda tympani to four basic taste stimuli were investigated electrophysiologically in rats. When the TTX (10 mg/ml) was applied directly to the tongue surface for 3 minutes, magnitude of the integrated responses of the chorda tympani was diminished to about 60% of that of the control response. This diminution of response was recovered within 30 minutes by degrees and the effect of the TTX was antagonized by guanylate. This result gives a suggestion that guanidyl group in the TTX may play an important role for the inhibitory actions to the responses of the chorda tympani. On the other hand, when the TTX (0.25 mg/100 g b. wt.) was applied intravenously, magnitude of the responses of the chorda tympani to four basic taste stimuli decreased gradually to 20 approximately 30% of that of the control responses within 60 minutes and did not recover more than 10 hours. This is assumed due to the blocking of the sodium pump of nerve fibers in the chorda tympani by the TTX.", "contents": "[A study on the gustatory effects of tetrodotoxin in rat (author's transl)]. Effects of tetrodotoxin (TTX) on neural responses of the chorda tympani to four basic taste stimuli were investigated electrophysiologically in rats. When the TTX (10 mg/ml) was applied directly to the tongue surface for 3 minutes, magnitude of the integrated responses of the chorda tympani was diminished to about 60% of that of the control response. This diminution of response was recovered within 30 minutes by degrees and the effect of the TTX was antagonized by guanylate. This result gives a suggestion that guanidyl group in the TTX may play an important role for the inhibitory actions to the responses of the chorda tympani. On the other hand, when the TTX (0.25 mg/100 g b. wt.) was applied intravenously, magnitude of the responses of the chorda tympani to four basic taste stimuli decreased gradually to 20 approximately 30% of that of the control responses within 60 minutes and did not recover more than 10 hours. This is assumed due to the blocking of the sodium pump of nerve fibers in the chorda tympani by the TTX."}
{"id": "PMID:199723", "title": "Binding of LH and FSH to porcine granulosa cells during follicular maturation.", "content": "The uptake of 125I-labelled LH by equal numbers of granulosa cells from small, medium or large follicles was greater by cells from large follicles. In contrast, granulosa cells obtained from small follicles bound much more 125I-labelled FSH per cell than did cells obtained from medium and large follicles. Competition studies with unlabelled hormones indicated that porcine granulosa cells have specific receptors for LH and FSH. The addition of diethylstilboestrol enhanced the binding of 125I-labelled LH and inhibited the binding of 125I-labelled FSH to granulosa cells harvested from small and medium-sized follicles, but had no effect on those from large follicles.", "contents": "Binding of LH and FSH to porcine granulosa cells during follicular maturation. The uptake of 125I-labelled LH by equal numbers of granulosa cells from small, medium or large follicles was greater by cells from large follicles. In contrast, granulosa cells obtained from small follicles bound much more 125I-labelled FSH per cell than did cells obtained from medium and large follicles. Competition studies with unlabelled hormones indicated that porcine granulosa cells have specific receptors for LH and FSH. The addition of diethylstilboestrol enhanced the binding of 125I-labelled LH and inhibited the binding of 125I-labelled FSH to granulosa cells harvested from small and medium-sized follicles, but had no effect on those from large follicles."}
{"id": "PMID:199725", "title": "Radioreceptor assays: plasma membrane receptors and assays for polypeptide and glycoprotein hormones.", "content": "Receptors for peptide, protein and glycoprotein hormones, and the catecholamines are located on the plasma membranes of their target cells. Preparations of the receptors may be used as specific, high-affinity binding agents for these hormones in assay methodology akin to that for radioimmunoassay. A particular advantage of the radioreceptor assay is that it has a specificity directed towards the biologically active region of the hormone, rather than to some immunologically active region that may have little (or no) involvement in the expression of hormonal activity. Methods for hormone receptor preparation vary greatly, and range from the use of intact cells (as the source of hormone receptor) to the use of purified or solubilized membrane receptors. Receptors isolated from plasma membranes have proved to be of variable stability, and may be damaged during preparation and/or storage. Moreover, since they are present in relatively low concentration in the cell, their preparation in sufficient quantity for use in a radioreceptor assay may present technical problems. In general, there is good correlation between radioreceptor assays and in-vitro bioassays; differences between results from radioreceptor assays and radioimmunoassays are similar to those noted between in-vitro bioassays and radioimmunoassays. The sensitivity of the method is such that normal plasma concentrations of various hormones have been assayed by this technique.", "contents": "Radioreceptor assays: plasma membrane receptors and assays for polypeptide and glycoprotein hormones. Receptors for peptide, protein and glycoprotein hormones, and the catecholamines are located on the plasma membranes of their target cells. Preparations of the receptors may be used as specific, high-affinity binding agents for these hormones in assay methodology akin to that for radioimmunoassay. A particular advantage of the radioreceptor assay is that it has a specificity directed towards the biologically active region of the hormone, rather than to some immunologically active region that may have little (or no) involvement in the expression of hormonal activity. Methods for hormone receptor preparation vary greatly, and range from the use of intact cells (as the source of hormone receptor) to the use of purified or solubilized membrane receptors. Receptors isolated from plasma membranes have proved to be of variable stability, and may be damaged during preparation and/or storage. Moreover, since they are present in relatively low concentration in the cell, their preparation in sufficient quantity for use in a radioreceptor assay may present technical problems. In general, there is good correlation between radioreceptor assays and in-vitro bioassays; differences between results from radioreceptor assays and radioimmunoassays are similar to those noted between in-vitro bioassays and radioimmunoassays. The sensitivity of the method is such that normal plasma concentrations of various hormones have been assayed by this technique."}
{"id": "PMID:199727", "title": "Synthesis of beta-spiro[pyrrolidinoindolines], their binding to the glycine receptor, and in vivo biological acitivity.", "content": "A series of beta-spiro[pyrrolidinoindolines], 3a-d, was prepared and evaluated for their ability to bind to the glycine receptor. These compounds were also tested in vivo to determine if they would produce convulsant or anxiolytic effects. The target indolines were chosen because they represent rings A, B, E, and a portion of ring C of strychnine. Results of this study indicate that, in this series, an acetylindoline in the endo configuration and a tertiary amine, such as that of the pyrrolidine ring nitrogen, are required for biological activity. In all of the cases studied, the activity was of a convulsant rather than a relaxant nature. Excellent correlation was found to exist between the binding affinities to the strychnine site of the glycine receptor and clonic convulsions (ED50) and death (LD50) in the mouse.", "contents": "Synthesis of beta-spiro[pyrrolidinoindolines], their binding to the glycine receptor, and in vivo biological acitivity. A series of beta-spiro[pyrrolidinoindolines], 3a-d, was prepared and evaluated for their ability to bind to the glycine receptor. These compounds were also tested in vivo to determine if they would produce convulsant or anxiolytic effects. The target indolines were chosen because they represent rings A, B, E, and a portion of ring C of strychnine. Results of this study indicate that, in this series, an acetylindoline in the endo configuration and a tertiary amine, such as that of the pyrrolidine ring nitrogen, are required for biological activity. In all of the cases studied, the activity was of a convulsant rather than a relaxant nature. Excellent correlation was found to exist between the binding affinities to the strychnine site of the glycine receptor and clonic convulsions (ED50) and death (LD50) in the mouse."}
{"id": "PMID:199728", "title": "Heterocyclic and piperonylic acid esters of 1-methyl-4-piperidinol as analgesics.", "content": "Heterocyclic and piperonylic acid esters of 1-methyl-4-piperidinol were synthesized and evaluated for analgesic activity. 1-Methyl-4-piperidinol 4-piperonylate (14) exhibited activity in the codeine range (mouse hot plate). In monkeys, 14 acted neither as a typical narcotic agonist nor as a typical antagonist and it showed no physical dependence liability of the morphine type. The nonquaternary C-4 peperidinol esters 1a, 4, 8, and 14 exhibited marginal to virtually no binding to the opiate receptor in rat brain homogenates. The interaction of various functional groups of this series with potential binding sites of a nonopiate type receptor is discussed.", "contents": "Heterocyclic and piperonylic acid esters of 1-methyl-4-piperidinol as analgesics. Heterocyclic and piperonylic acid esters of 1-methyl-4-piperidinol were synthesized and evaluated for analgesic activity. 1-Methyl-4-piperidinol 4-piperonylate (14) exhibited activity in the codeine range (mouse hot plate). In monkeys, 14 acted neither as a typical narcotic agonist nor as a typical antagonist and it showed no physical dependence liability of the morphine type. The nonquaternary C-4 peperidinol esters 1a, 4, 8, and 14 exhibited marginal to virtually no binding to the opiate receptor in rat brain homogenates. The interaction of various functional groups of this series with potential binding sites of a nonopiate type receptor is discussed."}
{"id": "PMID:199729", "title": "Synthesis and biological activity of two metabolites of 1-methyl-5-(1-methylethyl)-2-nitro-1 H-imidazole, an antiprotozoal agent.", "content": "5-(-Hydroxyl-1-methylethyl-)-1-methyl-2-nitro-1 H-imidazole (6) and 5-(1,2-dihydroxyl-1-methylethyl)-1-methyl-2-nitro-1 H-imidazole (9) are the principal metabolites found in urines of animals (mice, rats, and dogs) treated with 1-methyl-5-(1-methylethyl)-2-nitro-1 H-imidazole (1), an effective antitrichomonas agent. These two metabolites have been synthesized. Compound 6 was found to be less toxic than the parent compound 1 and to possess essentially the same activity against Trichomonas vaginalis in experimental infections. Compound 9 showed a low degree of in vivo activity.", "contents": "Synthesis and biological activity of two metabolites of 1-methyl-5-(1-methylethyl)-2-nitro-1 H-imidazole, an antiprotozoal agent. 5-(-Hydroxyl-1-methylethyl-)-1-methyl-2-nitro-1 H-imidazole (6) and 5-(1,2-dihydroxyl-1-methylethyl)-1-methyl-2-nitro-1 H-imidazole (9) are the principal metabolites found in urines of animals (mice, rats, and dogs) treated with 1-methyl-5-(1-methylethyl)-2-nitro-1 H-imidazole (1), an effective antitrichomonas agent. These two metabolites have been synthesized. Compound 6 was found to be less toxic than the parent compound 1 and to possess essentially the same activity against Trichomonas vaginalis in experimental infections. Compound 9 showed a low degree of in vivo activity."}
{"id": "PMID:199730", "title": "Radioimmunoassay of herpes-simplex and measles virus antibodies in serum and cerebrospinal fluid of patients without infectious or demyelinating diseases of the central nervous system.", "content": "A solid-phase radioimmunoassay was used to detect IgG antibodies against herpes-simplex virus antigens (capsid, envelope and excreted) and against measles virus antigen in serum and cerebrospinal fluid (CSF) specimens of 61 patients with no evidence of infectious or demyelinating disease of the central nervous system. Quantitative determinations of IgG and albumin in serum and CSF were also performed. Of the 61 serum and 61 CSF samples tested, 57 and 56 respectively contained antibodies against subunit antigens of herpes simplex virus. Antibody against measles virus was found in 59 serum and 47 CSF specimens. A positive correlation (P less than 0-001) was found between each of the four serum to CSF antibody ratios and the serum to CSF total IgG ratios. This indicated that the distribution of antiviral IgG antibodies in serum and CSF normally follows the distribution of total IgG. The ratios between viral antibody in serum and CSF were also correlated with albumin ratios (P less than 0-05). An inverse relation (P less than 0-001) was found between the age of the patients and their serum to CSF albumin ratios, but not their IgG ratios, suggesting that the albumin ratio is a useful indicator of a blood brain barrier lesion and that the IgG ratio should be used in evaluating disturbed antibody ratios.", "contents": "Radioimmunoassay of herpes-simplex and measles virus antibodies in serum and cerebrospinal fluid of patients without infectious or demyelinating diseases of the central nervous system. A solid-phase radioimmunoassay was used to detect IgG antibodies against herpes-simplex virus antigens (capsid, envelope and excreted) and against measles virus antigen in serum and cerebrospinal fluid (CSF) specimens of 61 patients with no evidence of infectious or demyelinating disease of the central nervous system. Quantitative determinations of IgG and albumin in serum and CSF were also performed. Of the 61 serum and 61 CSF samples tested, 57 and 56 respectively contained antibodies against subunit antigens of herpes simplex virus. Antibody against measles virus was found in 59 serum and 47 CSF specimens. A positive correlation (P less than 0-001) was found between each of the four serum to CSF antibody ratios and the serum to CSF total IgG ratios. This indicated that the distribution of antiviral IgG antibodies in serum and CSF normally follows the distribution of total IgG. The ratios between viral antibody in serum and CSF were also correlated with albumin ratios (P less than 0-05). An inverse relation (P less than 0-001) was found between the age of the patients and their serum to CSF albumin ratios, but not their IgG ratios, suggesting that the albumin ratio is a useful indicator of a blood brain barrier lesion and that the IgG ratio should be used in evaluating disturbed antibody ratios."}
{"id": "PMID:199731", "title": "Cytomegaloviru; antibody in the urine of renal transplant patients.", "content": "Small amounts of cytomegalovirus (CMV) antibody were detected in the urine of renal transplant patients excreting the virus. The antibody was probably produced locally, as a result of active CMV infection of the urinary tract.", "contents": "Cytomegaloviru; antibody in the urine of renal transplant patients. Small amounts of cytomegalovirus (CMV) antibody were detected in the urine of renal transplant patients excreting the virus. The antibody was probably produced locally, as a result of active CMV infection of the urinary tract."}
{"id": "PMID:199733", "title": "Interaction of Simian Virus 40 chromatin with Simian Virus 40 T-antigen.", "content": "We have studied the binding of the tumor antigen (T-antigen) of simian virus 40 to simian virus 40 chromatin (minichromosomes). The minichromosomes isolated from infected cells by a modification of standard techniques were relatively free of contaminating RNA and cellular DNA and had a ratio (by weight) of protein to DNA of approximately 1; their DNA was 50 to 60% digestible to an acid-soluble form by staphylococcal nuclease. Cleavage of this chromatin with restriction endonucleases indicated that the nuclease-resistant regions were randomly distributed in the population of minichromosomes, but were not randomly distributed within minichromosomes. Only 20 to 35% of these minichromosomes adsorbed nonspecifically to nitrocellulose filters, permitting binding studies between simian virus 40 T-antigen and chromatin to be performed. Approximately two to three times as much T-antigen was required to bind chromatin as to bind an equivalent amount of free DNA.  When T-antigen was present in excess, both chromatin and free DNA were quantitatively retained on the filters. On the other hand, when DNA or chromatin was present in excess, only one-third as much chromatin as DNA was retained. We suggest that T-antigen-chromatin complexes may be formed by the cooperative binding of T-antigen to chromatin, whereas T-antigen-DNA complexes may be formed by simple bimolecular interactions.", "contents": "Interaction of Simian Virus 40 chromatin with Simian Virus 40 T-antigen. We have studied the binding of the tumor antigen (T-antigen) of simian virus 40 to simian virus 40 chromatin (minichromosomes). The minichromosomes isolated from infected cells by a modification of standard techniques were relatively free of contaminating RNA and cellular DNA and had a ratio (by weight) of protein to DNA of approximately 1; their DNA was 50 to 60% digestible to an acid-soluble form by staphylococcal nuclease. Cleavage of this chromatin with restriction endonucleases indicated that the nuclease-resistant regions were randomly distributed in the population of minichromosomes, but were not randomly distributed within minichromosomes. Only 20 to 35% of these minichromosomes adsorbed nonspecifically to nitrocellulose filters, permitting binding studies between simian virus 40 T-antigen and chromatin to be performed. Approximately two to three times as much T-antigen was required to bind chromatin as to bind an equivalent amount of free DNA.  When T-antigen was present in excess, both chromatin and free DNA were quantitatively retained on the filters. On the other hand, when DNA or chromatin was present in excess, only one-third as much chromatin as DNA was retained. We suggest that T-antigen-chromatin complexes may be formed by the cooperative binding of T-antigen to chromatin, whereas T-antigen-DNA complexes may be formed by simple bimolecular interactions."}
{"id": "PMID:199734", "title": "Herpes simplex virus DNA polymerase as the site of phosphonoacetate sensitivity: temperature-sensitive mutants.", "content": "Temperature-sensitive (ts) mutants in a number of complementation groups of herpes simplex virus type 1 (HSV-1) are deficient in DNA polymerase induction at the restrictive temperature. Twenty-two mutants in 15 complementation groups were tested for sensitivity to phosphonoacetate (PAA), a compound that inhibits HSV replication in vivo and the DNA polymerase in vitro. One mutant, tsD9, was resistant to PAA (Pr), whereas all others were sensitive. Revertants of tsD9 to the ts+ phenotype simultaneously lost PAA resistance. Additional Pr mutants were isolated from ts mutants belonging to several complementation groups of HSV-1. Double mutants (ts Pr phenotype) were used in three-factor recombination analyses to locate the PAA locus on the genetic map at a position indistinguishable from the ts lesion in tsD9. In all cases, resistance or sensitivity to PAA in vivo was correlated with resistance or sensitivity of DNA polymerase in vitro. These data are compatible with the temperature-sensitive lesion of tsD9 and the determinant of PAA sensitivity both residing in the structural gene for DNA polymerase.", "contents": "Herpes simplex virus DNA polymerase as the site of phosphonoacetate sensitivity: temperature-sensitive mutants. Temperature-sensitive (ts) mutants in a number of complementation groups of herpes simplex virus type 1 (HSV-1) are deficient in DNA polymerase induction at the restrictive temperature. Twenty-two mutants in 15 complementation groups were tested for sensitivity to phosphonoacetate (PAA), a compound that inhibits HSV replication in vivo and the DNA polymerase in vitro. One mutant, tsD9, was resistant to PAA (Pr), whereas all others were sensitive. Revertants of tsD9 to the ts+ phenotype simultaneously lost PAA resistance. Additional Pr mutants were isolated from ts mutants belonging to several complementation groups of HSV-1. Double mutants (ts Pr phenotype) were used in three-factor recombination analyses to locate the PAA locus on the genetic map at a position indistinguishable from the ts lesion in tsD9. In all cases, resistance or sensitivity to PAA in vivo was correlated with resistance or sensitivity of DNA polymerase in vitro. These data are compatible with the temperature-sensitive lesion of tsD9 and the determinant of PAA sensitivity both residing in the structural gene for DNA polymerase."}
{"id": "PMID:199735", "title": "Characterization of RNA from equine infectious anemia virus.", "content": "The genome of equine infectious anemia virus, a nononcogenic retrovirus, has been characterized by velocity sedimentation, electrophoresis in polyacrylamide gels, buoyant density in CS2SO4, and susceptibility to nuclease digestion. The nucleic acid of purified virus was resolved by sedimentation analysis into a fast-sedimenting genome component, which comprises about two-thirds of the virion RNA, and a slow-sedimenting RNA, which is probably comprised of host-derived tRNA and a trace amount of 5S RNA. The fast-sedimenting RNA had a sedimentation coefficient of 62S and a molecular weight of 5.4 X 10(6) to 5.6 X 10(6), as determined by sedimentation velocity and electrophoretic mobility. Upon heat denaturation, [3H]uridine-labeled 62S RNA dissociated into material comprised of 90 to 95% single-stranded species, sedimenting predominantly at 34S, with a molecular weight of 2.7 X 10(6) to 2.9 X 10(6) and 5 to 10% 4S RNA. The 62S RNA was predominantly single-stranded but contained double-stranded regions, as indicated by partial resistance to RNase IA and SI nuclease and by a lower buoyant density in CS2SO4 than that of the single-stranded 34S RNA derived by heat denaturation. These data indicated that the viral genome consisted of two 34S subunits of single-stranded RNA held in a high-molecular-weight complex with 4S RNA by a mechanism involving a small degree of base pairing. Thus, the structure of equine infectious anemia virus RNA is similar to that of other retroviruses.", "contents": "Characterization of RNA from equine infectious anemia virus. The genome of equine infectious anemia virus, a nononcogenic retrovirus, has been characterized by velocity sedimentation, electrophoresis in polyacrylamide gels, buoyant density in CS2SO4, and susceptibility to nuclease digestion. The nucleic acid of purified virus was resolved by sedimentation analysis into a fast-sedimenting genome component, which comprises about two-thirds of the virion RNA, and a slow-sedimenting RNA, which is probably comprised of host-derived tRNA and a trace amount of 5S RNA. The fast-sedimenting RNA had a sedimentation coefficient of 62S and a molecular weight of 5.4 X 10(6) to 5.6 X 10(6), as determined by sedimentation velocity and electrophoretic mobility. Upon heat denaturation, [3H]uridine-labeled 62S RNA dissociated into material comprised of 90 to 95% single-stranded species, sedimenting predominantly at 34S, with a molecular weight of 2.7 X 10(6) to 2.9 X 10(6) and 5 to 10% 4S RNA. The 62S RNA was predominantly single-stranded but contained double-stranded regions, as indicated by partial resistance to RNase IA and SI nuclease and by a lower buoyant density in CS2SO4 than that of the single-stranded 34S RNA derived by heat denaturation. These data indicated that the viral genome consisted of two 34S subunits of single-stranded RNA held in a high-molecular-weight complex with 4S RNA by a mechanism involving a small degree of base pairing. Thus, the structure of equine infectious anemia virus RNA is similar to that of other retroviruses."}
{"id": "PMID:199736", "title": "Measurement of proviral genes in uninfected and avian myeloblastosis virus-infected cells by hybridization with 3H-labeled complementary DNA probe excess.", "content": "Viral RNA (vRNA) from avian myeloblastosis virus or DNA from virus-infected and uninfected cells was hybridized with [3H]DNA complementary to viral RNA ([3H]cDNA) under conditions of [3H]cDNA excess. When [3H]cDNA was used to drive the hybridization reaction with vRNA, a rate constant of 33.2 liters/mol-s was obtained. The same rate constant was obtained when vRNA excess was used as the driver. The specific activities of the [3H]DNA probe, estimated from kinetic measurements of the hybridization reaction and from the amount of [3H]cDNA in hybrid form at equilibrium, were 9.1 and 8.6 cpm/pg, respectively. DNA isolated from uninfected cells contained five or six copies of proviral DNA per cell genome. DNA isolated from erythrocytes infected with avian myeloblastosis virus had an additional five or six viral genes added to the cell genome, and the virus-infected target cell (myeloblasts) contained about 15 additional copies of proviral DNA per cell. The use of excess [3H]cDNA probe is an easy and accurate method to quantify the frequency of proviral DNA sequences in cell DNA and to measure a small amount (40 to 200 pg) of vRNA. Probe excess hybridization offers a number of advantages over other procedures and these are discussed.", "contents": "Measurement of proviral genes in uninfected and avian myeloblastosis virus-infected cells by hybridization with 3H-labeled complementary DNA probe excess. Viral RNA (vRNA) from avian myeloblastosis virus or DNA from virus-infected and uninfected cells was hybridized with [3H]DNA complementary to viral RNA ([3H]cDNA) under conditions of [3H]cDNA excess. When [3H]cDNA was used to drive the hybridization reaction with vRNA, a rate constant of 33.2 liters/mol-s was obtained. The same rate constant was obtained when vRNA excess was used as the driver. The specific activities of the [3H]DNA probe, estimated from kinetic measurements of the hybridization reaction and from the amount of [3H]cDNA in hybrid form at equilibrium, were 9.1 and 8.6 cpm/pg, respectively. DNA isolated from uninfected cells contained five or six copies of proviral DNA per cell genome. DNA isolated from erythrocytes infected with avian myeloblastosis virus had an additional five or six viral genes added to the cell genome, and the virus-infected target cell (myeloblasts) contained about 15 additional copies of proviral DNA per cell. The use of excess [3H]cDNA probe is an easy and accurate method to quantify the frequency of proviral DNA sequences in cell DNA and to measure a small amount (40 to 200 pg) of vRNA. Probe excess hybridization offers a number of advantages over other procedures and these are discussed."}
{"id": "PMID:199737", "title": "Nucleotide sequences derived from pheasant DNA in the genome of recombinant avian leukosis viruses with subgroup F specificity.", "content": "Recombination between viral and cellular genes can give rise to new strains of retroviruses. For example, Rous-associated virus 61 (RAV-61) is a recombinant between the Bryan high-titer strain of Rous sarcoma virus (RSV) and normal pheasant DNA. Nucleic acid hybridization techniques were used to study the genome of RAV-61 and another RAV with subgroup F specificity (RAV-F) obtained by passage of RSV-RAV-0 in cells from a ring-necked pheasant embryo. The nucleotide sequences acquired by these two independent isolates of RAV-F that were not shared with the parental virus comprised 20 to 25% of the RAV-F genomes and were indistinguishable by nucleic acid hybridization. (In addition, RAV-F genomes had another set of nucleotide sequences that were homologous to some pheasant nucleotide sequences and also were present in the parental viruses.) A specific complementary DNA, containing only nucleotide sequences complementary to those acquired by RAV-61 through recombination, was prepared. These nucleotide sequences were pheasant derived and were not present in the genomes of reticuloendotheliosis viruses, pheasant viruses, and avian leukosis-sarcoma viruses of subgroups A, B, C, D, and E. They were partially endogenous, however, to avian DNA other than pheasant. The fraction of these nucleotide sequences present in other avian DNAs generally paralleled the genetic relatedness of these avian species to pheasants. However, there was a high degree of homology between these pheasant nucleotide sequences and related nucleotide sequences in the DNA of normal chickens as indicated by the identical melting profiles of the respective hybrids.", "contents": "Nucleotide sequences derived from pheasant DNA in the genome of recombinant avian leukosis viruses with subgroup F specificity. Recombination between viral and cellular genes can give rise to new strains of retroviruses. For example, Rous-associated virus 61 (RAV-61) is a recombinant between the Bryan high-titer strain of Rous sarcoma virus (RSV) and normal pheasant DNA. Nucleic acid hybridization techniques were used to study the genome of RAV-61 and another RAV with subgroup F specificity (RAV-F) obtained by passage of RSV-RAV-0 in cells from a ring-necked pheasant embryo. The nucleotide sequences acquired by these two independent isolates of RAV-F that were not shared with the parental virus comprised 20 to 25% of the RAV-F genomes and were indistinguishable by nucleic acid hybridization. (In addition, RAV-F genomes had another set of nucleotide sequences that were homologous to some pheasant nucleotide sequences and also were present in the parental viruses.) A specific complementary DNA, containing only nucleotide sequences complementary to those acquired by RAV-61 through recombination, was prepared. These nucleotide sequences were pheasant derived and were not present in the genomes of reticuloendotheliosis viruses, pheasant viruses, and avian leukosis-sarcoma viruses of subgroups A, B, C, D, and E. They were partially endogenous, however, to avian DNA other than pheasant. The fraction of these nucleotide sequences present in other avian DNAs generally paralleled the genetic relatedness of these avian species to pheasants. However, there was a high degree of homology between these pheasant nucleotide sequences and related nucleotide sequences in the DNA of normal chickens as indicated by the identical melting profiles of the respective hybrids."}
{"id": "PMID:199738", "title": "Role of potassium in the synthesis and decay of two specific bacteriophage T4 messages.", "content": "The role of K+ in the in vivo metabolism of specific phage T4 messengers was studied. By using a mutant of Escherichia coli defective in its ability to accumulate K+ from the growth medium, it was possible to rapidly deplete cells of their intracellular K+ and in this way determine K+-dependent reactions in vivo. The rate constants for accumulation, synthesis, and decay of the early enzymes deoxynucleotide kinase and alpha-glucosyl transferase were determined. It was shown that there is a very close association between mRNA synthesis and its decay, indicating that a mechanism may be present in the cell that can regulate the concentration of these RNAs. Since the mRNA's for these enzymes are very stable in cells depleted of K+, K+ depletion may be a useful method for the isolation of functional T4 mRNA.", "contents": "Role of potassium in the synthesis and decay of two specific bacteriophage T4 messages. The role of K+ in the in vivo metabolism of specific phage T4 messengers was studied. By using a mutant of Escherichia coli defective in its ability to accumulate K+ from the growth medium, it was possible to rapidly deplete cells of their intracellular K+ and in this way determine K+-dependent reactions in vivo. The rate constants for accumulation, synthesis, and decay of the early enzymes deoxynucleotide kinase and alpha-glucosyl transferase were determined. It was shown that there is a very close association between mRNA synthesis and its decay, indicating that a mechanism may be present in the cell that can regulate the concentration of these RNAs. Since the mRNA's for these enzymes are very stable in cells depleted of K+, K+ depletion may be a useful method for the isolation of functional T4 mRNA."}
{"id": "PMID:199739", "title": "Recombination between endogenous and exogenous simian virus 40 genes. I. Rescue of a simian virus 40 temperature-sensitive mutant by passage in permissive transformed monkey lines.", "content": "Passage of the simian virus 40 (SV40) temperature-sensitive (ts) mutant tsD202 at the permissive temperature in each of three permissive lines of SV40-transformed monkey CV1 cells resulted in the emergence of temperature-insensitive virus, which plated like wild-type SV40 at the restrictive temperature on normal CV1 cells. In independent experiments, the amount of temperature-insensitive virus that appeared after passage on transformed cells was from 10(3)- to 10(6)-fold greater than the amount of ts-revertant virus that appeared after an equal number of passages in nontransformed CV1 cells. The virus rescued by passage on transformed cells bred true upon sequential plaque purification, plated on normal CV1 cells with single-hit kinetics at the restrictive temperature, and displayed no selective growth advantage on transformed cells compared to non-transformed cells. Hence, the reversion of the ts phenotype is neither due to complementation effects nor to the selection of preexisting revertants, which grow better on transformed cells. In the accompanying article (T. Vogel et al., J. Virol. 24:541-550, 1977), we present biochemical evidence that the rescue of tsD202 mediated by passage on transformed cells is due to recombination with the resident SV40 genome. Parallel experiments in which tsA, tsB, and tsC SV40 mutants were passaged in each of the three permissive lines of SV40-transformed monkey cells resulted in either only borderline levels of rescue (tsA mutants) or no detectable rescue (tsB and tsC mutants). Evidence is presented that the resident SV40 genome of the transformed monkey lines is itself a late ts mutant, and we suggest that this accounts for the lack of detectable rescue of the tsB and tsC mutants. We furthermore suggest that the borderline level of rescue observed with two tsA mutants is related to a previous finding (Y. Gluzman et al., J. Virol. 22:256-266, 1977) which indicated that the resident SV40 genome of the permissive transformed monkey cells is defective in the function required for initiation of viral DNA synthesis.", "contents": "Recombination between endogenous and exogenous simian virus 40 genes. I. Rescue of a simian virus 40 temperature-sensitive mutant by passage in permissive transformed monkey lines. Passage of the simian virus 40 (SV40) temperature-sensitive (ts) mutant tsD202 at the permissive temperature in each of three permissive lines of SV40-transformed monkey CV1 cells resulted in the emergence of temperature-insensitive virus, which plated like wild-type SV40 at the restrictive temperature on normal CV1 cells. In independent experiments, the amount of temperature-insensitive virus that appeared after passage on transformed cells was from 10(3)- to 10(6)-fold greater than the amount of ts-revertant virus that appeared after an equal number of passages in nontransformed CV1 cells. The virus rescued by passage on transformed cells bred true upon sequential plaque purification, plated on normal CV1 cells with single-hit kinetics at the restrictive temperature, and displayed no selective growth advantage on transformed cells compared to non-transformed cells. Hence, the reversion of the ts phenotype is neither due to complementation effects nor to the selection of preexisting revertants, which grow better on transformed cells. In the accompanying article (T. Vogel et al., J. Virol. 24:541-550, 1977), we present biochemical evidence that the rescue of tsD202 mediated by passage on transformed cells is due to recombination with the resident SV40 genome. Parallel experiments in which tsA, tsB, and tsC SV40 mutants were passaged in each of the three permissive lines of SV40-transformed monkey cells resulted in either only borderline levels of rescue (tsA mutants) or no detectable rescue (tsB and tsC mutants). Evidence is presented that the resident SV40 genome of the transformed monkey lines is itself a late ts mutant, and we suggest that this accounts for the lack of detectable rescue of the tsB and tsC mutants. We furthermore suggest that the borderline level of rescue observed with two tsA mutants is related to a previous finding (Y. Gluzman et al., J. Virol. 22:256-266, 1977) which indicated that the resident SV40 genome of the permissive transformed monkey cells is defective in the function required for initiation of viral DNA synthesis."}
{"id": "PMID:199740", "title": "Recombination between endogenous and exogenous simian virus 40 genes. II. Biochemical evidence for genetic exchange.", "content": "The genome of the simian virus 40 (SV40) temperature-sensitive (ts) mutant tsD202 rescued by passage on transformed permissive monkey lines (see accompanying paper [Y. Gluzman et al., J. Virol. 24:534-540, 1977]) was analyzed by restriction endonuclease cleavage mapping to obtain biochemical evidence that the rescue of the ts phenotype results from recombination with the resident SV40 genome of the transformed cell. It was demonstrated that the endonuclease R. HaeIII cleavage site, which is located at 0.9 map unit in the standard viral genome (and which is in the proximity of the known map position of the tsD lesion), is missing in the DNAs of the parental tsD202 virus and of three independent revertants of tsD202. In contrast, this cleavage site was shown to be present in the DNAs of four out of five independently derived rescued D202 populations and in the DNA of the SV40 strain, 777, used to transform the monkey cells. Comparison of the endonuclease R. Hin(II + III) cleavage patterns of SV40 strain 777 DNA and tsD202 DNA revealed differences in the electrophoretic mobilities of Hin fragments A, B, and F. However, the corresponding Hin fragments from all four rescued D202 genomes were identical in their mobilities to those of tsD202 DNA, indicating that these regions of the rescued D202 genome are characteristic of the tsD202 parent. We conclude, therefore, that the genome of the rescued D202 virus is a true recombinant, since it contains restriction endonuclease cleavage sites characteristic of both parents, the endogenous resident SV40 genome of the transformed monkey cells and the exogenous tsD202 mutant.", "contents": "Recombination between endogenous and exogenous simian virus 40 genes. II. Biochemical evidence for genetic exchange. The genome of the simian virus 40 (SV40) temperature-sensitive (ts) mutant tsD202 rescued by passage on transformed permissive monkey lines (see accompanying paper [Y. Gluzman et al., J. Virol. 24:534-540, 1977]) was analyzed by restriction endonuclease cleavage mapping to obtain biochemical evidence that the rescue of the ts phenotype results from recombination with the resident SV40 genome of the transformed cell. It was demonstrated that the endonuclease R. HaeIII cleavage site, which is located at 0.9 map unit in the standard viral genome (and which is in the proximity of the known map position of the tsD lesion), is missing in the DNAs of the parental tsD202 virus and of three independent revertants of tsD202. In contrast, this cleavage site was shown to be present in the DNAs of four out of five independently derived rescued D202 populations and in the DNA of the SV40 strain, 777, used to transform the monkey cells. Comparison of the endonuclease R. Hin(II + III) cleavage patterns of SV40 strain 777 DNA and tsD202 DNA revealed differences in the electrophoretic mobilities of Hin fragments A, B, and F. However, the corresponding Hin fragments from all four rescued D202 genomes were identical in their mobilities to those of tsD202 DNA, indicating that these regions of the rescued D202 genome are characteristic of the tsD202 parent. We conclude, therefore, that the genome of the rescued D202 virus is a true recombinant, since it contains restriction endonuclease cleavage sites characteristic of both parents, the endogenous resident SV40 genome of the transformed monkey cells and the exogenous tsD202 mutant."}
{"id": "PMID:199741", "title": "Characterization of Gazdar murine sarcoma virus by nucleic acid hybridization and analysis of viral expression in cells.", "content": "Gazdar murine sarcoma virus (Gz-MSV) and Moloney murine sarcoma virus (M-MSV) are closely related. The complete M-MSV-specific nucleic acid sequences constituted a major portion of Gz-MSV-specific sequences. The MSV-specific sequences in both Gz-MSV and M-MSV genomes shared homology with hamster leukemia virus nucleic acid sequences. Both rat cells (S+L+) and hamster (S+L-) cells expressed two viral proteins of 68,000 and 70,000 daltons. These proteins were immunologically related to p60 purified from m1 virions of M-MSV.", "contents": "Characterization of Gazdar murine sarcoma virus by nucleic acid hybridization and analysis of viral expression in cells. Gazdar murine sarcoma virus (Gz-MSV) and Moloney murine sarcoma virus (M-MSV) are closely related. The complete M-MSV-specific nucleic acid sequences constituted a major portion of Gz-MSV-specific sequences. The MSV-specific sequences in both Gz-MSV and M-MSV genomes shared homology with hamster leukemia virus nucleic acid sequences. Both rat cells (S+L+) and hamster (S+L-) cells expressed two viral proteins of 68,000 and 70,000 daltons. These proteins were immunologically related to p60 purified from m1 virions of M-MSV."}
{"id": "PMID:199742", "title": "Alterations of neutral glycolipids in cells infected with syncytium-producing mutants of herpes simplex virus type 1.", "content": "The isolation of syncytium-producing mutants of herpes simplex virus type 1 (KOS strain), which cause extensive cell fusion during otherwise normal infections, has been reported previously (S. Person, R. W. Knowles, G. S. Read, S. C. Warner, and V. C. Bond, J. Virol. 17:183-190, 1976). Seven of these mutants, plus two syncytial strains obtained elsewhere, were used to compare the incorporation of labeled galactose into neutral glycolipids of mock-infected, wild-type-infected, and syncytially infected human embryonic lung cells. Five predominant cellular glycolipid species were observed, denoted GL-1 through GL-5 in order of increasing oligosaccharide chain length; for example, GL-1 and GL-2 correspond to glycolipids that contain mono- and disaccharide units, respectively. Wild-type virus infection caused an increase in galactose incorporation into GL-1 and GL-2 relative to GL-3 through GL-5. For a single labeling interval from 4 to 10 h after adsorption, syncytial infections generally resulted in a relatively greater incorporation into more complex glycolipids than did wild-type infections. One mutant, syn 20, was compared with wild-type virus throughout infection by using a series of shorter labeling pulses and appeared to delay by at least 2 h the alterations observed during wild-type infections. These alterations are apparently due to defects in synthesis, since prelabeled cellular glycolipids were not differentially degraded during mock or virus infection.", "contents": "Alterations of neutral glycolipids in cells infected with syncytium-producing mutants of herpes simplex virus type 1. The isolation of syncytium-producing mutants of herpes simplex virus type 1 (KOS strain), which cause extensive cell fusion during otherwise normal infections, has been reported previously (S. Person, R. W. Knowles, G. S. Read, S. C. Warner, and V. C. Bond, J. Virol. 17:183-190, 1976). Seven of these mutants, plus two syncytial strains obtained elsewhere, were used to compare the incorporation of labeled galactose into neutral glycolipids of mock-infected, wild-type-infected, and syncytially infected human embryonic lung cells. Five predominant cellular glycolipid species were observed, denoted GL-1 through GL-5 in order of increasing oligosaccharide chain length; for example, GL-1 and GL-2 correspond to glycolipids that contain mono- and disaccharide units, respectively. Wild-type virus infection caused an increase in galactose incorporation into GL-1 and GL-2 relative to GL-3 through GL-5. For a single labeling interval from 4 to 10 h after adsorption, syncytial infections generally resulted in a relatively greater incorporation into more complex glycolipids than did wild-type infections. One mutant, syn 20, was compared with wild-type virus throughout infection by using a series of shorter labeling pulses and appeared to delay by at least 2 h the alterations observed during wild-type infections. These alterations are apparently due to defects in synthesis, since prelabeled cellular glycolipids were not differentially degraded during mock or virus infection."}
{"id": "PMID:199743", "title": "RNase T1-resistant oligonucleotides of an N- and a B-tropic murine leukemia virus of BALB/c: evidence for recombination between these viruses.", "content": "We used two-dimensional gel electrophoresis to obtain fingerprints of 32P-labeled RNase T1-resistant oligonucleotides derived from the genomes of an N- and a B-tropic murine leukemia virus of BALB/c. These viruses share approximately 30 large T1-resistant oligonucleotides. In addition, there are eight large oligonucleotides unique to the N-tropic virus, and there are six B-trophic virus-specific oligonucleotides. Viruses, designated XLP-N, which appear by biological criteria and analysis of virion proteins to be recombinants between these N- and B-tropic viruses, possess some but not all of the N or B virus-specific oligonucleotides.", "contents": "RNase T1-resistant oligonucleotides of an N- and a B-tropic murine leukemia virus of BALB/c: evidence for recombination between these viruses. We used two-dimensional gel electrophoresis to obtain fingerprints of 32P-labeled RNase T1-resistant oligonucleotides derived from the genomes of an N- and a B-tropic murine leukemia virus of BALB/c. These viruses share approximately 30 large T1-resistant oligonucleotides. In addition, there are eight large oligonucleotides unique to the N-tropic virus, and there are six B-trophic virus-specific oligonucleotides. Viruses, designated XLP-N, which appear by biological criteria and analysis of virion proteins to be recombinants between these N- and B-tropic viruses, possess some but not all of the N or B virus-specific oligonucleotides."}
{"id": "PMID:199744", "title": "RNase T1-resistant oligonucleotides of Akv-1 and Akv-2 type C viruses of AKR mice.", "content": "We used two-dimensional gel electrophoresis to obtain fingerprints of RNase T1-resistant oligonucleotides derived from the genomes of Akv-1 and Akv-2 type C viruses of AKR mice. The fingerprints of these two viruses look identical. The products of pancreatic RNase digestion of corresponding oligonucleotides of the two viruses were indistinguishable. These observations are consistent with, but not proof of, the possible identity of the genomes of the Akv-1 and Akv-2 viruses and, thus, of the viral genetic material believed to comprise the Akv-1 and Akv-2 loci of AKR mice.", "contents": "RNase T1-resistant oligonucleotides of Akv-1 and Akv-2 type C viruses of AKR mice. We used two-dimensional gel electrophoresis to obtain fingerprints of RNase T1-resistant oligonucleotides derived from the genomes of Akv-1 and Akv-2 type C viruses of AKR mice. The fingerprints of these two viruses look identical. The products of pancreatic RNase digestion of corresponding oligonucleotides of the two viruses were indistinguishable. These observations are consistent with, but not proof of, the possible identity of the genomes of the Akv-1 and Akv-2 viruses and, thus, of the viral genetic material believed to comprise the Akv-1 and Akv-2 loci of AKR mice."}
{"id": "PMID:199745", "title": "Measurements of the genome sizes of simian virus 40 and polyoma virus.", "content": "We have measured the genome sizes of simian virus 40 and polyoma virus and found them to be 5,010 +/- 125 base pairs and 5,080 +/- 125 base pairs, respectively.", "contents": "Measurements of the genome sizes of simian virus 40 and polyoma virus. We have measured the genome sizes of simian virus 40 and polyoma virus and found them to be 5,010 +/- 125 base pairs and 5,080 +/- 125 base pairs, respectively."}
{"id": "PMID:199746", "title": "BALB/3T3 cells infected by the ts3 mutant of polyoma virus fail to accumulate virus-specific early RNA at the nonpermissive temperature.", "content": "We measured the accumulation of virus-specific early RNA in BALB/3T3 cells infected by the ts3 mutant of polyoma virus by annealing cytoplasmic RNA from infected cells to purified, radiolabeled, \"early\" strand of polyoma DNA. Cells infected by the ts3 mutant fail to accumulate virus-specific early RNA at the nonpermissive temperature.", "contents": "BALB/3T3 cells infected by the ts3 mutant of polyoma virus fail to accumulate virus-specific early RNA at the nonpermissive temperature. We measured the accumulation of virus-specific early RNA in BALB/3T3 cells infected by the ts3 mutant of polyoma virus by annealing cytoplasmic RNA from infected cells to purified, radiolabeled, \"early\" strand of polyoma DNA. Cells infected by the ts3 mutant fail to accumulate virus-specific early RNA at the nonpermissive temperature."}
{"id": "PMID:199747", "title": "The use of evoked electromyographic responses in diagnosing lesions of the cauda equina.", "content": "An electrophysiologic technique to evaluate the anatomic integrity of the peripheral pathways to the bladder and sphincters is described. Evoked electromyographic responses of the anal sphincter are produced by stimulating the bladder wall and urethra. Impulses travel via the pelvic nerves and cauda equina to the conus medullaris, activating the pudendal nerve nucleus and resulting in contraction of the external anal sphincter. Lesions along this pathway produce either prolonged latencies and depressed responses or complete loss of response. Correlation of the results of this technique in 110 patients with clinical myelographic and operative findings indicates that the technique is a useful clinical tool.", "contents": "The use of evoked electromyographic responses in diagnosing lesions of the cauda equina. An electrophysiologic technique to evaluate the anatomic integrity of the peripheral pathways to the bladder and sphincters is described. Evoked electromyographic responses of the anal sphincter are produced by stimulating the bladder wall and urethra. Impulses travel via the pelvic nerves and cauda equina to the conus medullaris, activating the pudendal nerve nucleus and resulting in contraction of the external anal sphincter. Lesions along this pathway produce either prolonged latencies and depressed responses or complete loss of response. Correlation of the results of this technique in 110 patients with clinical myelographic and operative findings indicates that the technique is a useful clinical tool."}
{"id": "PMID:199748", "title": "Paget's disease of the scrotum presenting as an inguinal lymph node.", "content": "Extramammary Paget's disease is a rare malignant entity. A case with a unique clinical presentation is described and emphasis is placed on the need for early biopsy of skin lesions in the genital area.", "contents": "Paget's disease of the scrotum presenting as an inguinal lymph node. Extramammary Paget's disease is a rare malignant entity. A case with a unique clinical presentation is described and emphasis is placed on the need for early biopsy of skin lesions in the genital area."}
{"id": "PMID:199749", "title": "Evidence for the association of cytomegalovirus with carcinoma of the prostate.", "content": "A human genital isolate of cytomegalovirus is shown to have transformed human embryonic lung cells in vitro. These cells produce tumors when injected into athymic nude mice. Two cell lines derived from tissue from human prostatic carcinoma have survived more than 20 passages in vitro and demonstrate cytomegalovirus-specific membrane antigen. Significant humoral antibody titers against cytomegalovirus have been demonstrated. Cell-mediated lymphocytotoxicity against these transformed cells has been demonstrated in patients with urinary tract tumors. This evidence indicates that an association between cytomegalovirus and human prostatic cancer may be more than coincidental.", "contents": "Evidence for the association of cytomegalovirus with carcinoma of the prostate. A human genital isolate of cytomegalovirus is shown to have transformed human embryonic lung cells in vitro. These cells produce tumors when injected into athymic nude mice. Two cell lines derived from tissue from human prostatic carcinoma have survived more than 20 passages in vitro and demonstrate cytomegalovirus-specific membrane antigen. Significant humoral antibody titers against cytomegalovirus have been demonstrated. Cell-mediated lymphocytotoxicity against these transformed cells has been demonstrated in patients with urinary tract tumors. This evidence indicates that an association between cytomegalovirus and human prostatic cancer may be more than coincidental."}
{"id": "PMID:199750", "title": "Pheochromocytoma with prominent calcification and associated pancreatic islet cell tumor.", "content": "A case of bilateral pheochromocytoma with an associated pancreatic islet cell tumor is reported. Prominent calcification was noted in the left adrenal tumor.", "contents": "Pheochromocytoma with prominent calcification and associated pancreatic islet cell tumor. A case of bilateral pheochromocytoma with an associated pancreatic islet cell tumor is reported. Prominent calcification was noted in the left adrenal tumor."}
{"id": "PMID:199751", "title": "Poxvirus fibromas on African hares.", "content": "Small dermal tumors were found on three African hares (Lepus capensis) in the Laikipia District, Kenya. Gross and histopathologic studies revealed similarities to the Shope's fibroma of wild rabbits in North America and fibromas of European hares. Histological examination of the African hare fibromas revealed intracytoplasmic inclusion bodies characteristic of poxviruses and poxvirus virions were demonstrated by electron microscopy of ultrathin sections. Attempts to propagate the virus in rabbit skin, embryonated chicken eggs and cell cultures were unsuccessful.", "contents": "Poxvirus fibromas on African hares. Small dermal tumors were found on three African hares (Lepus capensis) in the Laikipia District, Kenya. Gross and histopathologic studies revealed similarities to the Shope's fibroma of wild rabbits in North America and fibromas of European hares. Histological examination of the African hare fibromas revealed intracytoplasmic inclusion bodies characteristic of poxviruses and poxvirus virions were demonstrated by electron microscopy of ultrathin sections. Attempts to propagate the virus in rabbit skin, embryonated chicken eggs and cell cultures were unsuccessful."}
{"id": "PMID:199752", "title": "Primary liver tumors and oral contraceptives. Results of a survey.", "content": "Data on 378 (in females) and 165 (in males) cases of primary liver tumors reported by 477 hospitals in the United States during 1970 to 1975 show that in males, 91.5% of the tumors were malignant, and in females, 43.9% were malignant and 59.1% were benign. Of the 212 benign tumors in females, 96 were hepatic cell adenomas and 58 were focal nodular hyperplasias. A history of oral contraceptive use was found in nearly half of all women: 65% with benign tumors, 74% with hepatic cell adenomas, and 74% with focal nodular hyperplasias. Symptoms were more severe among users. No case of intraperitoneal bleeding was observed in nonusers. The findings confirm the suggested association between oral contraceptive use and hepatic cell adenomas and focal nodular hyperplasias.", "contents": "Primary liver tumors and oral contraceptives. Results of a survey. Data on 378 (in females) and 165 (in males) cases of primary liver tumors reported by 477 hospitals in the United States during 1970 to 1975 show that in males, 91.5% of the tumors were malignant, and in females, 43.9% were malignant and 59.1% were benign. Of the 212 benign tumors in females, 96 were hepatic cell adenomas and 58 were focal nodular hyperplasias. A history of oral contraceptive use was found in nearly half of all women: 65% with benign tumors, 74% with hepatic cell adenomas, and 74% with focal nodular hyperplasias. Symptoms were more severe among users. No case of intraperitoneal bleeding was observed in nonusers. The findings confirm the suggested association between oral contraceptive use and hepatic cell adenomas and focal nodular hyperplasias."}
{"id": "PMID:199753", "title": "Plasma high-density lipoprotein cholesterol level. Influence of risk factor intervention.", "content": "Determinants of circulating high density lipoproteins (HDL) were sought in 301 men studied during a year of participation in a coronary prevention program. Mean plasma HDL-cholesterol concentration rose by 2.8 mg/dl (6%) in the group receiving multifactor intervention, but the change did not differ significantly from that in the comparison group. Larger changes in both directions were seen in many individuals. Multiple regression analysis of these changes indicates that increased plasma HDL levels occur when plasma triglyceride level is decreased, cigarette smoking is reduced, and habitual alcohol intake is increased. Increases in the concentration of HDL-cholesterol also tended to accompany adherence to the fat-controlled diet, reduction in LDL-cholesterol level, and loss of body weight. Conventional coronary prevention programs are unlikely to have an adverse influence on this new, risk-lowering factor.", "contents": "Plasma high-density lipoprotein cholesterol level. Influence of risk factor intervention. Determinants of circulating high density lipoproteins (HDL) were sought in 301 men studied during a year of participation in a coronary prevention program. Mean plasma HDL-cholesterol concentration rose by 2.8 mg/dl (6%) in the group receiving multifactor intervention, but the change did not differ significantly from that in the comparison group. Larger changes in both directions were seen in many individuals. Multiple regression analysis of these changes indicates that increased plasma HDL levels occur when plasma triglyceride level is decreased, cigarette smoking is reduced, and habitual alcohol intake is increased. Increases in the concentration of HDL-cholesterol also tended to accompany adherence to the fat-controlled diet, reduction in LDL-cholesterol level, and loss of body weight. Conventional coronary prevention programs are unlikely to have an adverse influence on this new, risk-lowering factor."}
{"id": "PMID:199754", "title": "Peripheral diabetic neuropathy treated with amitriptyline and fluphenazine.", "content": "The pain of diabetic peripheral neuropathy responds poorly to current modes of treatment. We treated eight patients with this disorder whose pain was refractory to standard regimens but who experienced remarkable pain relief within two to five days after treatment with fluphenazine hydrochloride, amitriptyline hydrochloride, or a combination of the two. In four patients whose regimens were discontinued, pain recurred within two days and again remitted on reinstitution of the drug regimens. These findings suggest that fluphenazine alone or in combination with amitriptyline may be of benefit in treating the painful peripheral neuropathy associated with diabetes.", "contents": "Peripheral diabetic neuropathy treated with amitriptyline and fluphenazine. The pain of diabetic peripheral neuropathy responds poorly to current modes of treatment. We treated eight patients with this disorder whose pain was refractory to standard regimens but who experienced remarkable pain relief within two to five days after treatment with fluphenazine hydrochloride, amitriptyline hydrochloride, or a combination of the two. In four patients whose regimens were discontinued, pain recurred within two days and again remitted on reinstitution of the drug regimens. These findings suggest that fluphenazine alone or in combination with amitriptyline may be of benefit in treating the painful peripheral neuropathy associated with diabetes."}
{"id": "PMID:199755", "title": "Cytomegalovirus encephalitis in immunologically normal adults. Successful treatment with vidarabine.", "content": "Acute cytomegalovirus (CMV) encephalitis developed in two immunologically normal adults. The diagnosis was confirmed by isolation of CMV from the CSF and urine in one case and from temporal lobe biopsy tissue, CSF, and urine in the second case. Both patients were treated with vidarabine and showed dramatic clinical improvement. Virus excretion, which had been chronic in one case, cleared after therapy. To our knowledge, these are the first persons with CMV encephalitis evidenced by isolation of the virus from the CNS. The response to vidarabine was impressive and warrants further evaluation.", "contents": "Cytomegalovirus encephalitis in immunologically normal adults. Successful treatment with vidarabine. Acute cytomegalovirus (CMV) encephalitis developed in two immunologically normal adults. The diagnosis was confirmed by isolation of CMV from the CSF and urine in one case and from temporal lobe biopsy tissue, CSF, and urine in the second case. Both patients were treated with vidarabine and showed dramatic clinical improvement. Virus excretion, which had been chronic in one case, cleared after therapy. To our knowledge, these are the first persons with CMV encephalitis evidenced by isolation of the virus from the CNS. The response to vidarabine was impressive and warrants further evaluation."}
{"id": "PMID:199758", "title": "Probucol (Lorelco) in treatment of hyperlipemia.", "content": "The chemical structure of probucol differs from that of other hypolipemic agents, and its mechanism of action is unknown. This agent lowers elevated serum cholesterol (and low-density lipoprotein) levels and appears to be effective when used as an adjunct to a low-cholesterol, low-saturated-fat diet for treatment of type IIa hyperlipoproteinimia in adults; however, it is less effective than cholestyramine resin in patients with familial type IIa disorder. Although probucol has no consistent effect on elevated triglyceride levels, it may be useful as an adjunct to other drugs that lower these concentrations in patients with types IIb, III, and IV hyperlipoproteinemia when hypercholesterolemia persists. Probucol is generally well tolerated.", "contents": "Probucol (Lorelco) in treatment of hyperlipemia. The chemical structure of probucol differs from that of other hypolipemic agents, and its mechanism of action is unknown. This agent lowers elevated serum cholesterol (and low-density lipoprotein) levels and appears to be effective when used as an adjunct to a low-cholesterol, low-saturated-fat diet for treatment of type IIa hyperlipoproteinimia in adults; however, it is less effective than cholestyramine resin in patients with familial type IIa disorder. Although probucol has no consistent effect on elevated triglyceride levels, it may be useful as an adjunct to other drugs that lower these concentrations in patients with types IIb, III, and IV hyperlipoproteinemia when hypercholesterolemia persists. Probucol is generally well tolerated."}
{"id": "PMID:199769", "title": "Properties of thirteen kinds of adsorbents for removal of hydrogen sulfide, methanethiol, methyl sulfide, trimethylamine, and ammonia.", "content": "Adsorption of hydrogen sulfide, methanethiol, methyl sulfide, trimethylamine, and ammonia on thirteen kinds of adsorbents (5 kinds of silicate, 4 kinds of activated carbon, and 4 kinds of zeolite) was measured by gravimetry, at 30 degrees C and 50 Torr, using an adsorption apparatus with a spring balance in order to find the most suitable adsorbent for the removal of these gases by dry process. The relations between the amount of these gases adsorbed (mmol/cm2) on the adsorbent and the surface properties or the porous structure were examined to clarify the mechanism of adsorption of these gases on them through surface pH, pore size distribution, and area of an adsorbed particle of these gases. Among the thirteen adsorbents, the activated carbon Nos. 6 and 7 were the most suitable adsorbent for methanethiol, methyl sulfide, and trimethylamine whose area of an adsobed particle (wrho) was larger than about 17 A2, and zeolite Nos. 12 and 13 were most suitable for removal of hydrogen sulfide and ammonia (wrho less than about 17A2). The amount of these gases adsorbed (mmol/cm2) on these adsorbents was mainly determined by their porous structure rather than by their surface properties.", "contents": "Properties of thirteen kinds of adsorbents for removal of hydrogen sulfide, methanethiol, methyl sulfide, trimethylamine, and ammonia. Adsorption of hydrogen sulfide, methanethiol, methyl sulfide, trimethylamine, and ammonia on thirteen kinds of adsorbents (5 kinds of silicate, 4 kinds of activated carbon, and 4 kinds of zeolite) was measured by gravimetry, at 30 degrees C and 50 Torr, using an adsorption apparatus with a spring balance in order to find the most suitable adsorbent for the removal of these gases by dry process. The relations between the amount of these gases adsorbed (mmol/cm2) on the adsorbent and the surface properties or the porous structure were examined to clarify the mechanism of adsorption of these gases on them through surface pH, pore size distribution, and area of an adsorbed particle of these gases. Among the thirteen adsorbents, the activated carbon Nos. 6 and 7 were the most suitable adsorbent for methanethiol, methyl sulfide, and trimethylamine whose area of an adsobed particle (wrho) was larger than about 17 A2, and zeolite Nos. 12 and 13 were most suitable for removal of hydrogen sulfide and ammonia (wrho less than about 17A2). The amount of these gases adsorbed (mmol/cm2) on these adsorbents was mainly determined by their porous structure rather than by their surface properties."}
{"id": "PMID:199770", "title": "Studies on the respiratory system of Aspergillus oryzae. V. Some properties of the respiratory system of mitochondria from mycelia grown in the presence of chloramphenicol.", "content": "Presence of chloramphenicol in the growth medium for mycelia of Aspergillus oryzae was without effect on the oxidative activity, respiratory control, or P/O ratio of isolated mitochondria. The mitochondria oxidized Krebs cycle intermediates even in the presence of cyanide at the concentration markedly inhibiting the normal mitochondrial oxidation. However, the P/O ratio during the mitochondrial oxidation decreased by about 1.0 on addition of cyanide. The c-type cytochromes, shown to occur in large amounts than in normal mitochondria (Wakiyama and Ogura, 1972), were suggested to act as electron carriers in this cyanide-resistant oxidation. A novel pigment, demonstrated only in the mitochondria prepared from chloramphenicol-treated mycelia by a CO-difference spectrum, was presumed to be the terminal oxidase of the respiration in the presence of cyanide.", "contents": "Studies on the respiratory system of Aspergillus oryzae. V. Some properties of the respiratory system of mitochondria from mycelia grown in the presence of chloramphenicol. Presence of chloramphenicol in the growth medium for mycelia of Aspergillus oryzae was without effect on the oxidative activity, respiratory control, or P/O ratio of isolated mitochondria. The mitochondria oxidized Krebs cycle intermediates even in the presence of cyanide at the concentration markedly inhibiting the normal mitochondrial oxidation. However, the P/O ratio during the mitochondrial oxidation decreased by about 1.0 on addition of cyanide. The c-type cytochromes, shown to occur in large amounts than in normal mitochondria (Wakiyama and Ogura, 1972), were suggested to act as electron carriers in this cyanide-resistant oxidation. A novel pigment, demonstrated only in the mitochondria prepared from chloramphenicol-treated mycelia by a CO-difference spectrum, was presumed to be the terminal oxidase of the respiration in the presence of cyanide."}
{"id": "PMID:199772", "title": "Depressive effect of epinephrine mediated via adrenergic beta-receptor in isolated rat colon and duodenum.", "content": "Differences in sensitivity to catecholamines between colon and duodenum were examined in tissues from the rat, monitoring the depressive effect of catecholamines on contractile response to acetylcholine (ACh). The sensitivity of colonic tissue to ACh was higher than that of duodenal. Epinephrine (Ep, 10(-7) g/ml) depressed the contractile response to ACh in the colonic tissue, but not in the duodenal. The depressive effect of Ep on the contractile response to ACh is attributed to the stimulation of adrenergic beta-receptors in the colonic tissue as the depression disappeared by pretreatment with propranolol (10(-6) g/ml). There was no difference on the depressive effect of papaverine on the contractile response to ACh, except when low concentrations were used. Dibutyryl cyclic AMP (10(-4) g/ml) depressed the contractile responses of both tissues to ACh. After treatment with Ep (10(-7) g/ml), cyclic AMP content was increased in the colonic tissue but not in the duodenal. However, papaverine (3 X 10(-6 g/ml) and a higher dose of Ep(10(-6) g/ml) increased cyclic AMP content in both tissues. The increase of cyclic AMP and the decrease of tension caused by Ep were not correlated in these tissues. However, a positive correlation was observed between the depressive effect of Ep on the contractile response to ACh and the increase of cyclic AMP content in these tissues.", "contents": "Depressive effect of epinephrine mediated via adrenergic beta-receptor in isolated rat colon and duodenum. Differences in sensitivity to catecholamines between colon and duodenum were examined in tissues from the rat, monitoring the depressive effect of catecholamines on contractile response to acetylcholine (ACh). The sensitivity of colonic tissue to ACh was higher than that of duodenal. Epinephrine (Ep, 10(-7) g/ml) depressed the contractile response to ACh in the colonic tissue, but not in the duodenal. The depressive effect of Ep on the contractile response to ACh is attributed to the stimulation of adrenergic beta-receptors in the colonic tissue as the depression disappeared by pretreatment with propranolol (10(-6) g/ml). There was no difference on the depressive effect of papaverine on the contractile response to ACh, except when low concentrations were used. Dibutyryl cyclic AMP (10(-4) g/ml) depressed the contractile responses of both tissues to ACh. After treatment with Ep (10(-7) g/ml), cyclic AMP content was increased in the colonic tissue but not in the duodenal. However, papaverine (3 X 10(-6 g/ml) and a higher dose of Ep(10(-6) g/ml) increased cyclic AMP content in both tissues. The increase of cyclic AMP and the decrease of tension caused by Ep were not correlated in these tissues. However, a positive correlation was observed between the depressive effect of Ep on the contractile response to ACh and the increase of cyclic AMP content in these tissues."}
{"id": "PMID:199773", "title": "Effects of p-chlorophenylalanine (p-CPA) on sleep in olfactory bulb lesioned rats.", "content": "The effect of p-CPA and 5-HTP followed by p-CPA on sleep was studied in rats with olfactory bulb lesions (O.B. lesioned rats). In these rats, electrodes were chronically implanted to record the EEG (frontal cortex and dorsal hippocampus), the cervical electromyogram and eye movements. The REM sleep stage was selectively decreased from 24 to 32 hours after 200 mg/kg of p-CPA in the sham lesioned rats, whereas both the slow wave sleep and REM sleep stages were markedly decreased by the same dose of p-CPA in the O.B. lesioned rats. In both sham and O.B. lesioned groups, the slow wave sleep and REM sleep stages decreased from 24 to 32 hours after 400 mg/kg of p-CPA and the percentage of decrease in the slow wave sleep stage was much larger with 400 mg/kg of p-CPA than with 200 mg/kg and 400 mg/kg of p-CPA. In the O.B. lesioned rats, the insomnia produced by 200 mg/kg and 400 mg/kg of p-CPA disappeared with 5-HTP (5 mg/kg). On the other hand, the insomnia produced by 200 mg/kg of p-CPA did not recur with 5-HTP in the sham lesioned rats, but with 400 mg/kg there was a recurrence. These results suggest that the enhanced effect of p-CPA and 5-HTP followed by p-CPA in the O.B. lesioned rats is due to changes in the sensitivity of the serotonergic system in the brain.", "contents": "Effects of p-chlorophenylalanine (p-CPA) on sleep in olfactory bulb lesioned rats. The effect of p-CPA and 5-HTP followed by p-CPA on sleep was studied in rats with olfactory bulb lesions (O.B. lesioned rats). In these rats, electrodes were chronically implanted to record the EEG (frontal cortex and dorsal hippocampus), the cervical electromyogram and eye movements. The REM sleep stage was selectively decreased from 24 to 32 hours after 200 mg/kg of p-CPA in the sham lesioned rats, whereas both the slow wave sleep and REM sleep stages were markedly decreased by the same dose of p-CPA in the O.B. lesioned rats. In both sham and O.B. lesioned groups, the slow wave sleep and REM sleep stages decreased from 24 to 32 hours after 400 mg/kg of p-CPA and the percentage of decrease in the slow wave sleep stage was much larger with 400 mg/kg of p-CPA than with 200 mg/kg and 400 mg/kg of p-CPA. In the O.B. lesioned rats, the insomnia produced by 200 mg/kg and 400 mg/kg of p-CPA disappeared with 5-HTP (5 mg/kg). On the other hand, the insomnia produced by 200 mg/kg of p-CPA did not recur with 5-HTP in the sham lesioned rats, but with 400 mg/kg there was a recurrence. These results suggest that the enhanced effect of p-CPA and 5-HTP followed by p-CPA in the O.B. lesioned rats is due to changes in the sensitivity of the serotonergic system in the brain."}
{"id": "PMID:199774", "title": "Potentiation of the NGF-mediated nerve fiber outgrowth by ginsenoside Rb1 in organ cultures of chicken dorsal root ganglia.", "content": "The fiber outgrowth induced by ACh, dibutyryl cyclic AMP and dibutyryl cyclic GMP in explanted chick embryonic dorsal root ganglia differed distinctly from that be nerve growth factor (NGF) and submandibular gland extract of adult male mice. Ginsenoside Rb1 potentiated the effects of NGF and submandibular extract at concentrations of 3 and 30 muM, but did not potentiate the effects of ACh, dibutyryl cyclic AMP and dibutyryl cyclic GMP. NGF-antibody inhibited the effects of NGF, but not the effects of ACh, dibutyryl cyclic AMP and dibutyryl cyclic GMP, Concanavalin A and KCL did not promote fiber outgrowth.", "contents": "Potentiation of the NGF-mediated nerve fiber outgrowth by ginsenoside Rb1 in organ cultures of chicken dorsal root ganglia. The fiber outgrowth induced by ACh, dibutyryl cyclic AMP and dibutyryl cyclic GMP in explanted chick embryonic dorsal root ganglia differed distinctly from that be nerve growth factor (NGF) and submandibular gland extract of adult male mice. Ginsenoside Rb1 potentiated the effects of NGF and submandibular extract at concentrations of 3 and 30 muM, but did not potentiate the effects of ACh, dibutyryl cyclic AMP and dibutyryl cyclic GMP. NGF-antibody inhibited the effects of NGF, but not the effects of ACh, dibutyryl cyclic AMP and dibutyryl cyclic GMP, Concanavalin A and KCL did not promote fiber outgrowth."}
{"id": "PMID:199778", "title": "The integrated trauma service concept.", "content": "An integrated trauma service, through coordination of pre-existing manpower and resources, insures the availability of medical care to patients suffering unforeseen or critical physical injuries and their sequelae. Provided an examination of the overall emergency medical service capabilities of the community dictates the need for a trauma service, the first step is to secure a surgeon interested in the care of the trauma patient. Cooperation of physician colleagues is gained by a policy of mandatory consultation whenever injuries involve specialty areas. Trauma service involvement begins with prioritization, resuscitation, and assessment of the patient in the emergency department and extends through definitive care, management of injury sequelae and rehabilitation. The \"isolated injury\" is defined by the trauma service and the appropriate specialty service notified. Injuries involving two or more body systems dictate admission to the trauma service except for the patient with an unstable cervical spine injury or deteriorating neurologic status. Under such circumstances, a neurosurgical admission is instituted and the trauma service consults. When the trauma service is operational, educational programs, data collection and retrieval, and follow-up care are enhanced.", "contents": "The integrated trauma service concept. An integrated trauma service, through coordination of pre-existing manpower and resources, insures the availability of medical care to patients suffering unforeseen or critical physical injuries and their sequelae. Provided an examination of the overall emergency medical service capabilities of the community dictates the need for a trauma service, the first step is to secure a surgeon interested in the care of the trauma patient. Cooperation of physician colleagues is gained by a policy of mandatory consultation whenever injuries involve specialty areas. Trauma service involvement begins with prioritization, resuscitation, and assessment of the patient in the emergency department and extends through definitive care, management of injury sequelae and rehabilitation. The \"isolated injury\" is defined by the trauma service and the appropriate specialty service notified. Injuries involving two or more body systems dictate admission to the trauma service except for the patient with an unstable cervical spine injury or deteriorating neurologic status. Under such circumstances, a neurosurgical admission is instituted and the trauma service consults. When the trauma service is operational, educational programs, data collection and retrieval, and follow-up care are enhanced."}
{"id": "PMID:199816", "title": "Progressive necrotizing external otitis: treatment with ticarcillin and tobramycin.", "content": "The history of necrotizing external otitis, its diagnosis and management are reviewed. A case history is presented of a patient who was diagnosed as having progressive necrotizing external otitis with facial paralysis. In spite of standard medical treatment and aggressive surgical management, the disease process continued with progressive involvement of Cranial nerves IX and X. The Pseudomonas aeruginosa bacteria developed an increased minimal inhibitory concentration (MIC) to carbenicillin and gentamicin by requiring near toxic blood levels to be effective. Investigational ticarcillin (alpha-carboxy-3-thienylmethylpenicillin) and tobramycin were used successfully in resolving the infection.", "contents": "Progressive necrotizing external otitis: treatment with ticarcillin and tobramycin. The history of necrotizing external otitis, its diagnosis and management are reviewed. A case history is presented of a patient who was diagnosed as having progressive necrotizing external otitis with facial paralysis. In spite of standard medical treatment and aggressive surgical management, the disease process continued with progressive involvement of Cranial nerves IX and X. The Pseudomonas aeruginosa bacteria developed an increased minimal inhibitory concentration (MIC) to carbenicillin and gentamicin by requiring near toxic blood levels to be effective. Investigational ticarcillin (alpha-carboxy-3-thienylmethylpenicillin) and tobramycin were used successfully in resolving the infection."}
{"id": "PMID:199817", "title": "Viral particles in nasopharyngeal carcinoma.", "content": "Lymphoepithelioma of the nasopharynx was identified in a 17-year-old Chinese male. The Epstein-Barr virus titer was 1:3200. Tissue from the tumor mass was prepared for electron microscopy. Particles consistent with the morphological characteristics of herpes virus were found within the cytoplasm of malignant epithelial cells. This finding is discussed in relation to other data suggesting an oncogenic role of herpes virus in human malignancy.", "contents": "Viral particles in nasopharyngeal carcinoma. Lymphoepithelioma of the nasopharynx was identified in a 17-year-old Chinese male. The Epstein-Barr virus titer was 1:3200. Tissue from the tumor mass was prepared for electron microscopy. Particles consistent with the morphological characteristics of herpes virus were found within the cytoplasm of malignant epithelial cells. This finding is discussed in relation to other data suggesting an oncogenic role of herpes virus in human malignancy."}
{"id": "PMID:199826", "title": "The in vivo incorporation of [32P]-labeled orthophosphate into pyrophosphatidic acid and other phospholipids of Cryptococcus neoformans through cell growth.", "content": "Cryptococcus neoformans was cultured in a liquid medium containing [32P]-orthophosphate and harvested at various stages of cell growth. An aliquot of the [32P]-labeled cells was transferred to a nonradioactive medium, and the culture was continued again for some hours. The [32P]-radioactivity composition and the phosphorus composition of individual phospholipids relative to the total phospholipid through the incubation periods were estimated. Although levels of major phospholipids remained constant throughout the cell growth, the distribution pattern of the [32P]-radioactivity of individual phospholipids changed remarkably along with the progress of cell growth. The changing patterns of the specific radioactivities of individual phospholipids through the growth phase demonstrated that phosphatidic acid was one of the most active metabolites in phospholipids and that pyrophosphatidic acid was also metabolically active.", "contents": "The in vivo incorporation of [32P]-labeled orthophosphate into pyrophosphatidic acid and other phospholipids of Cryptococcus neoformans through cell growth. Cryptococcus neoformans was cultured in a liquid medium containing [32P]-orthophosphate and harvested at various stages of cell growth. An aliquot of the [32P]-labeled cells was transferred to a nonradioactive medium, and the culture was continued again for some hours. The [32P]-radioactivity composition and the phosphorus composition of individual phospholipids relative to the total phospholipid through the incubation periods were estimated. Although levels of major phospholipids remained constant throughout the cell growth, the distribution pattern of the [32P]-radioactivity of individual phospholipids changed remarkably along with the progress of cell growth. The changing patterns of the specific radioactivities of individual phospholipids through the growth phase demonstrated that phosphatidic acid was one of the most active metabolites in phospholipids and that pyrophosphatidic acid was also metabolically active."}
{"id": "PMID:199830", "title": "[Structure and function of virus-induced antigens in cultured cells infected with Merek's disease and turkey herpes viruses. II. Isolation of intracellular antigens from infected cells (author's transl)].", "content": "Virus-induced antigens were isolated from MDV and HVT-infected cells by salt extraction with 3M KCl and purified by Con.A chromatography and isoelectric focusing. Electrophoretic analysis of 35S-methionine, 3H-fucose and 32P-orthophosphate labeled antigens revealed 7 different polypeptides, two of them containing labeled carbohydrates, and one phospholipid component. The isolated virus-induced antigens from infected cells were identified as serologically active membrane complexes carrying common antigenic determinants of MDV and HVT. They were able to bind to virus-neutralizing immunglobulins as shown by antibody binding tests. Summarizing the presented analytic and serologic findings it was proposed to classify MDV and HVT as different serotypes of a common Marek's disease virus group.", "contents": "[Structure and function of virus-induced antigens in cultured cells infected with Merek's disease and turkey herpes viruses. II. Isolation of intracellular antigens from infected cells (author's transl)]. Virus-induced antigens were isolated from MDV and HVT-infected cells by salt extraction with 3M KCl and purified by Con.A chromatography and isoelectric focusing. Electrophoretic analysis of 35S-methionine, 3H-fucose and 32P-orthophosphate labeled antigens revealed 7 different polypeptides, two of them containing labeled carbohydrates, and one phospholipid component. The isolated virus-induced antigens from infected cells were identified as serologically active membrane complexes carrying common antigenic determinants of MDV and HVT. They were able to bind to virus-neutralizing immunglobulins as shown by antibody binding tests. Summarizing the presented analytic and serologic findings it was proposed to classify MDV and HVT as different serotypes of a common Marek's disease virus group."}
{"id": "PMID:199831", "title": "Hepatitis A-virus particles in stools of patients from a natural hepatitis outbreak in Germany.", "content": "During a hepatitis outbreak in Southern Germany 27 nm particles were visualized by immune electron microscopy in stools of two patients. These particles were sereologically identical or similar to hepatitis A-virus particles identified in the USA. The buoyant density of these particles was 1.34 g/cm3 as shown by cesium chloride density centrifugation. The particles were first observed in small numbers in a stool obtained 11 days, and in large numbers in stools obtained 6 and 7 days before the onset of jaundice. Few particles were seen on the day of the onset of jaundice and none thereafter. In both patients a sereoconversion to hepatitis A-virus as judged by immune electron microscopy could be demonstrated.", "contents": "Hepatitis A-virus particles in stools of patients from a natural hepatitis outbreak in Germany. During a hepatitis outbreak in Southern Germany 27 nm particles were visualized by immune electron microscopy in stools of two patients. These particles were sereologically identical or similar to hepatitis A-virus particles identified in the USA. The buoyant density of these particles was 1.34 g/cm3 as shown by cesium chloride density centrifugation. The particles were first observed in small numbers in a stool obtained 11 days, and in large numbers in stools obtained 6 and 7 days before the onset of jaundice. Few particles were seen on the day of the onset of jaundice and none thereafter. In both patients a sereoconversion to hepatitis A-virus as judged by immune electron microscopy could be demonstrated."}
{"id": "PMID:199832", "title": "Preparation in undenatured form of the main protein bound to heterogeneous nuclear RNA in liver and hepatoma cells.", "content": "Particles carrying heterogeneous nuclear RNA (30 S-particles) were prepared from rat liver and Zajdela hepatoma ascites cell nuclei after ultrasonic disruption. The ribonucleoprotein structures were disintegrated in the presence of 100mM spermidine. Using chromatography on Sepharose-polyadenylate a protein component has been obtained which possessed high affinity for heterogeneous nuclear RNA, polyuridylate and polyadenylate, and double-stranded DNA. This protein was the main species of the ribonucleoprotein studied; it showed bands with molcular weights of 37000 and 40000 respectively in SDS gel electrophoresis. The RNA-binding proteins isolated from liver and hepatoma had identical molecular weights and the same affinity for Sepharose-polyadenylate used in the isolation.", "contents": "Preparation in undenatured form of the main protein bound to heterogeneous nuclear RNA in liver and hepatoma cells. Particles carrying heterogeneous nuclear RNA (30 S-particles) were prepared from rat liver and Zajdela hepatoma ascites cell nuclei after ultrasonic disruption. The ribonucleoprotein structures were disintegrated in the presence of 100mM spermidine. Using chromatography on Sepharose-polyadenylate a protein component has been obtained which possessed high affinity for heterogeneous nuclear RNA, polyuridylate and polyadenylate, and double-stranded DNA. This protein was the main species of the ribonucleoprotein studied; it showed bands with molcular weights of 37000 and 40000 respectively in SDS gel electrophoresis. The RNA-binding proteins isolated from liver and hepatoma had identical molecular weights and the same affinity for Sepharose-polyadenylate used in the isolation."}
{"id": "PMID:199833", "title": "Coding capacity of poly(A)+mRNA isolated from mengovirus-infected Ehrlich ascites tumor cells.", "content": "Total poly (A)+mRNA was isolated from mengovirus-infected Ehrlich ascites tumor cells at various times postinfection and quantitated in a cell-free system derived from uninfected ascites cells. Basic proteins were separated from acidic proteins by carboxymethyl cellulose chromatography. At the end of the infectious cycle, 8h postinfection, the cellular contents of most mRNAs coding for basic ribosomal proteins are still between 70 and 90 percent of those measured at the beginning of infection or in uninfected cells. On the basis of this result, the rapid shutoff of host protein synthesis after mengovirus infection of Ehrlich ascites tumor cells cannot be the consequence of the inactivation of host template RNA.", "contents": "Coding capacity of poly(A)+mRNA isolated from mengovirus-infected Ehrlich ascites tumor cells. Total poly (A)+mRNA was isolated from mengovirus-infected Ehrlich ascites tumor cells at various times postinfection and quantitated in a cell-free system derived from uninfected ascites cells. Basic proteins were separated from acidic proteins by carboxymethyl cellulose chromatography. At the end of the infectious cycle, 8h postinfection, the cellular contents of most mRNAs coding for basic ribosomal proteins are still between 70 and 90 percent of those measured at the beginning of infection or in uninfected cells. On the basis of this result, the rapid shutoff of host protein synthesis after mengovirus infection of Ehrlich ascites tumor cells cannot be the consequence of the inactivation of host template RNA."}
{"id": "PMID:199834", "title": "New directions in prostaglandin research and their possible implications for immunologic and nonimmunologic inflammation.", "content": "New information on prostaglandins and related structures derived from arachidonic acid is accumulating rapidly. Of particular interest is evidence for the existence of labile, highly biologically active, nonprostanoate derivatives. A role for the classic prostaglandins in immunologic inflammation is already strongly suspected, and it seems likely that the newly recognized arachidonic acid metabolites may prove to be even more important.", "contents": "New directions in prostaglandin research and their possible implications for immunologic and nonimmunologic inflammation. New information on prostaglandins and related structures derived from arachidonic acid is accumulating rapidly. Of particular interest is evidence for the existence of labile, highly biologically active, nonprostanoate derivatives. A role for the classic prostaglandins in immunologic inflammation is already strongly suspected, and it seems likely that the newly recognized arachidonic acid metabolites may prove to be even more important."}
{"id": "PMID:199836", "title": "A protective effect of caffeine on drosophila larvae treated with methyl methanesulfonate.", "content": "Lethality induced in larval populations of Drosophila melanogaster was recorded after treatment with (1) caffeine, (2) MMS or (3) caffeine plus MMS. The mixture of caffeine plus MMS was less toxic than expected from the effects observed after treatment with either substance individually. It is postulated that in the combined treatment the caffeine, by inhibiting semiconservative DNA replication, allows for some additional time for repair of alkylated DNA by a repair pathway which is not sensitive to caffeine, possibly excision repair.", "contents": "A protective effect of caffeine on drosophila larvae treated with methyl methanesulfonate. Lethality induced in larval populations of Drosophila melanogaster was recorded after treatment with (1) caffeine, (2) MMS or (3) caffeine plus MMS. The mixture of caffeine plus MMS was less toxic than expected from the effects observed after treatment with either substance individually. It is postulated that in the combined treatment the caffeine, by inhibiting semiconservative DNA replication, allows for some additional time for repair of alkylated DNA by a repair pathway which is not sensitive to caffeine, possibly excision repair."}
{"id": "PMID:199842", "title": "[Study of intracellular enzymes in the genus Schizosaccharomyces. Sistematic implications].", "content": "In the genus Schizosaccharomyces intracellular osidases and nitrite and nitrate reductases are revealed; particularly all the species possessing invertase, alpha-glucosidase and alpha-galactosidase. These characters underline the homogeneity on the genus. On the basis of osidases, nitrite and nitrate reductases results, 2 groups can be distinguished in this genus.", "contents": "[Study of intracellular enzymes in the genus Schizosaccharomyces. Sistematic implications]. In the genus Schizosaccharomyces intracellular osidases and nitrite and nitrate reductases are revealed; particularly all the species possessing invertase, alpha-glucosidase and alpha-galactosidase. These characters underline the homogeneity on the genus. On the basis of osidases, nitrite and nitrate reductases results, 2 groups can be distinguished in this genus."}
{"id": "PMID:199850", "title": "Immunodiffusion test in avian encephalomyelitis. I. Standardization of procedure and detection of antigen in infected chickens and embryos.", "content": "The double immunodiffusion technique was applied to avian encephalomyelitis virus (AEV). Agar gel medium containing such a high concentration of NaCl as 15% was more preferable for highly diluted quantities of reactants than any other NaCl-containing medium. A single precipitin line appeared on the 1st to 7th days of diffusion at room temperature. The specificity of reaction between AEV antigen and homologous immune chicken serum has been demonstrated by no cross reaction between heterologous viruses and specific absorption by homologous virus. The antigen was produced in the brain, viscera, eyeball, whole body and yolk sac of chick embryos inoculated via yolk sac, as well as in the thigh muscles of chicks subcutaneously inoculated at 2 days of age. Antigenicity was detectable in 50% emulsion of these organs with a virus titer more than 10(5.0) per 0.1 g of tissue weight.", "contents": "Immunodiffusion test in avian encephalomyelitis. I. Standardization of procedure and detection of antigen in infected chickens and embryos. The double immunodiffusion technique was applied to avian encephalomyelitis virus (AEV). Agar gel medium containing such a high concentration of NaCl as 15% was more preferable for highly diluted quantities of reactants than any other NaCl-containing medium. A single precipitin line appeared on the 1st to 7th days of diffusion at room temperature. The specificity of reaction between AEV antigen and homologous immune chicken serum has been demonstrated by no cross reaction between heterologous viruses and specific absorption by homologous virus. The antigen was produced in the brain, viscera, eyeball, whole body and yolk sac of chick embryos inoculated via yolk sac, as well as in the thigh muscles of chicks subcutaneously inoculated at 2 days of age. Antigenicity was detectable in 50% emulsion of these organs with a virus titer more than 10(5.0) per 0.1 g of tissue weight."}
{"id": "PMID:199851", "title": "Immunodiffusion test in avian encephalomyelitis. II. Detection of precipitating antibody in infected chickens in comparison with neutralizing antibody.", "content": "The sensitivities of double-immunodiffusion (DID) and neutralization tests to detect avian encephalomyelitis (AE) antibody in chickens were studied. Two antigens were employed in the tests. Concentrated antigen gave a higher titer of antiserum than crude antigen, which reacted only to serum having a neutralization log-index (NI) of 3.4approximately4.0 or more. Antibody responses were examined in four growing chick groups inoculated with AE virus by the intracerebral, subcutaneous and oral routes by the DID test with concentrated antigen and by the neutralization test for 1 or over 2 years after inoculation. When concentrated antigen was used, most sera having an NI of over 1.0 were positive for precipitating antibody. Therefore, the sensitivity of the DID test was nearly equal to that of the neutralization test. The DID test was considered to be applicable to the diagnosis of AE and an antibody survey in the field.", "contents": "Immunodiffusion test in avian encephalomyelitis. II. Detection of precipitating antibody in infected chickens in comparison with neutralizing antibody. The sensitivities of double-immunodiffusion (DID) and neutralization tests to detect avian encephalomyelitis (AE) antibody in chickens were studied. Two antigens were employed in the tests. Concentrated antigen gave a higher titer of antiserum than crude antigen, which reacted only to serum having a neutralization log-index (NI) of 3.4approximately4.0 or more. Antibody responses were examined in four growing chick groups inoculated with AE virus by the intracerebral, subcutaneous and oral routes by the DID test with concentrated antigen and by the neutralization test for 1 or over 2 years after inoculation. When concentrated antigen was used, most sera having an NI of over 1.0 were positive for precipitating antibody. Therefore, the sensitivity of the DID test was nearly equal to that of the neutralization test. The DID test was considered to be applicable to the diagnosis of AE and an antibody survey in the field."}
{"id": "PMID:199866", "title": "Nuclear localisation of DNA polymerase alpha and DNA synthesis in polyoma virus infected mouse cells.", "content": "Studies using inhibitors of DNA synthesis have shown that DNA polymerase alpha is located in nuclei of polyoma virus infected mouse cells to the same degree as these nuclei are engaged in DNA replication. These results indicate that either the enzyme is actively transported into nuclei concomitant with the onset of DNA synthesis, or that it is bound much more strongly in nuclei during DNA replication. In any case, these observations support the hypothesis that DNA polymerase alpha is involved in the replication of cellular and viral DNA.", "contents": "Nuclear localisation of DNA polymerase alpha and DNA synthesis in polyoma virus infected mouse cells. Studies using inhibitors of DNA synthesis have shown that DNA polymerase alpha is located in nuclei of polyoma virus infected mouse cells to the same degree as these nuclei are engaged in DNA replication. These results indicate that either the enzyme is actively transported into nuclei concomitant with the onset of DNA synthesis, or that it is bound much more strongly in nuclei during DNA replication. In any case, these observations support the hypothesis that DNA polymerase alpha is involved in the replication of cellular and viral DNA."}
{"id": "PMID:199867", "title": "The effect of eugenol on nerve transmission.", "content": "Because of its long-time use as a sedative or anodyne in dental procedures, eugenol was studied to determine its effect on evoked nerve impulse transmission. The sciatic nerve of the bullfrog was stimulated in a nerve chamber, and the compound action potential was visualized on and recorded from an oscilloscope screen. It was determined that eugenol concentrations ranging from 100 per cent to 0.01 per cent extinguished the impulse-transmission capabilities of the nerve within 3 hours. No reversal was observed within this time frame.", "contents": "The effect of eugenol on nerve transmission. Because of its long-time use as a sedative or anodyne in dental procedures, eugenol was studied to determine its effect on evoked nerve impulse transmission. The sciatic nerve of the bullfrog was stimulated in a nerve chamber, and the compound action potential was visualized on and recorded from an oscilloscope screen. It was determined that eugenol concentrations ranging from 100 per cent to 0.01 per cent extinguished the impulse-transmission capabilities of the nerve within 3 hours. No reversal was observed within this time frame."}
{"id": "PMID:199868", "title": "Radiographic manifestations of a lung carcinoma with metastases to the anterior maxilla.", "content": "Radiographic examination of the facial bones frequently reveals osteolytic and osteoblastic changes. A case of undifferentiated large-cell carcinoma of the lung with metastasis to the anterior maxilla is reported. Intraoral dental radiographs revealed an ill-defined lytic area in the left anterior maxilla. The periphery of the lesion revealed saberlike extensions of bone extending into the lytic defect. Cytologic and biopsy studies of the oral mucosa led to identification of the tumor as an undifferentiated large-cell carcinoma of the lung.", "contents": "Radiographic manifestations of a lung carcinoma with metastases to the anterior maxilla. Radiographic examination of the facial bones frequently reveals osteolytic and osteoblastic changes. A case of undifferentiated large-cell carcinoma of the lung with metastasis to the anterior maxilla is reported. Intraoral dental radiographs revealed an ill-defined lytic area in the left anterior maxilla. The periphery of the lesion revealed saberlike extensions of bone extending into the lytic defect. Cytologic and biopsy studies of the oral mucosa led to identification of the tumor as an undifferentiated large-cell carcinoma of the lung."}
{"id": "PMID:199871", "title": "Method for the determination of protein evolution rates by amino acid composition. Evolution rate of actins.", "content": "A method has been developed to determine the actin evolution rate. The method is based on amino acid compositon. The actin evolution rate has been established to be extremely low. Only three or less amino acid changes per hundred amino acid residues have accumulated for a 100 million years. One can explain the conservative nature of actin evolution as a sequence of its unique tightly fitted structure rich in biologically active centres at short distances from each other. The peculiar invariability of polar amino acids leads to a conclusion that some given distribution of charges is necessary for the unique functioning of actin molecules.", "contents": "Method for the determination of protein evolution rates by amino acid composition. Evolution rate of actins. A method has been developed to determine the actin evolution rate. The method is based on amino acid compositon. The actin evolution rate has been established to be extremely low. Only three or less amino acid changes per hundred amino acid residues have accumulated for a 100 million years. One can explain the conservative nature of actin evolution as a sequence of its unique tightly fitted structure rich in biologically active centres at short distances from each other. The peculiar invariability of polar amino acids leads to a conclusion that some given distribution of charges is necessary for the unique functioning of actin molecules."}
{"id": "PMID:199873", "title": "[A new antigonadotropin in the treatment of precocious puberty and pubertal gynaecomastia (author's transl)].", "content": "A synthetic steroid compound derived from testosteron (isoxazol-ethisterone), Danazol, with gonadotropin-depressing activity, was used in the treatment of 4 cases of idiopathis sexual precocity (age 2 1/2 to 4 years) and in 10 cases of severe pubertal gynaecomastia. In sexual precocity the suppression of menstruation as well as of breast-enlargement was good, while the suppression of acceleration of longitudinal growth and bone maturation was inferior compared with cyproteron-acetate. In most boys with gynaecomastia a marked regression of breast enlargement occurred within a few weeks or months. With the dosage used (200-300 mg/day in the sexual precocity patients, 300-400 mg in the gynaecomastia patients) the changes in plasma hormone levels (LH, FSH, progesterone, estradiol, testosterone) were within a non significant range. Depression of testosterone seemed to be a rather regular finding. No untoward side-effects of the medication were noticed in the 14 patients studied. In summary, Danazol did not show any advantages compared with the compounds used in the treatment of isosexual precocity sofar. In contrast, the drug proved to have useful effects in pubertal gynecomastia, a condition which in severe degrees certainly deserves medical treatment.", "contents": "[A new antigonadotropin in the treatment of precocious puberty and pubertal gynaecomastia (author's transl)]. A synthetic steroid compound derived from testosteron (isoxazol-ethisterone), Danazol, with gonadotropin-depressing activity, was used in the treatment of 4 cases of idiopathis sexual precocity (age 2 1/2 to 4 years) and in 10 cases of severe pubertal gynaecomastia. In sexual precocity the suppression of menstruation as well as of breast-enlargement was good, while the suppression of acceleration of longitudinal growth and bone maturation was inferior compared with cyproteron-acetate. In most boys with gynaecomastia a marked regression of breast enlargement occurred within a few weeks or months. With the dosage used (200-300 mg/day in the sexual precocity patients, 300-400 mg in the gynaecomastia patients) the changes in plasma hormone levels (LH, FSH, progesterone, estradiol, testosterone) were within a non significant range. Depression of testosterone seemed to be a rather regular finding. No untoward side-effects of the medication were noticed in the 14 patients studied. In summary, Danazol did not show any advantages compared with the compounds used in the treatment of isosexual precocity sofar. In contrast, the drug proved to have useful effects in pubertal gynecomastia, a condition which in severe degrees certainly deserves medical treatment."}
{"id": "PMID:199874", "title": "Response of gonadotropins to stimulation with luteinizing hormone -- releasing hormone (LH-RH) in children with precocious puberty before, during and following therapy with cyproterone acetate or an ethisterone derivate.", "content": "9 children with precocious puberty were treated over a period of 6 months to 6 3/12 years with Cyproteron acetate or an Ethisterone derivate. LH-RH tests with radioimmunological estimations of LH and FSH were performed before therapy was begun, during and after completion of treatment. In children with untreated precocious puberty the mean basal LH levels were the same as in normal prepubertal children but the increase and the peak values after i.v. LH-RH were found to be considerably greater than in normals. In the treated patients this stimulatable LH release was suppressed; after completion of therapy it was again elevated. The basal FSH levels in untreated children were elevated; however the increase and the peak values were comparable to the collective norm. Results were not altered considerably by therapy, however these parameters were given elevated after completion of therapy. Despite the marked suppression of stimulatable LH by therapy acceleration of bone age is practically not affected. After completion of therapy this drug-induced suppression of gonadotropines is promptly reversible.", "contents": "Response of gonadotropins to stimulation with luteinizing hormone -- releasing hormone (LH-RH) in children with precocious puberty before, during and following therapy with cyproterone acetate or an ethisterone derivate. 9 children with precocious puberty were treated over a period of 6 months to 6 3/12 years with Cyproteron acetate or an Ethisterone derivate. LH-RH tests with radioimmunological estimations of LH and FSH were performed before therapy was begun, during and after completion of treatment. In children with untreated precocious puberty the mean basal LH levels were the same as in normal prepubertal children but the increase and the peak values after i.v. LH-RH were found to be considerably greater than in normals. In the treated patients this stimulatable LH release was suppressed; after completion of therapy it was again elevated. The basal FSH levels in untreated children were elevated; however the increase and the peak values were comparable to the collective norm. Results were not altered considerably by therapy, however these parameters were given elevated after completion of therapy. Despite the marked suppression of stimulatable LH by therapy acceleration of bone age is practically not affected. After completion of therapy this drug-induced suppression of gonadotropines is promptly reversible."}
{"id": "PMID:199875", "title": "[Investigations of the urinary cAMP-excretion in pseudohypoparathyroidism (author's transl)].", "content": "Pseudohypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs and clinical and laboratory symptoms of hypoparathyroidism which is resistant however to parathyroid extract. ALBRIGHT and coworkers supposed that this resistance was caused by an inability of the renal tubules to respond to parathyroid hormone. On three children, suffering from PHP, we could demonstrate that parathyroid extract-resistance disappears during treatment with vitamin D. Measurements of urinary excretion of cAMP, the second messenger for parathyroid hormone, in the same patients showed low basal levels of this nucleotide, which could not be stimulated by parathyroid extract either before or during vitamin D-treatment. This constantly low and by parathyroid extract not stimulable cAMP-excretion is now the symptom with the most diagnostic value for PHP. Beyond this the finding of this defective urinary excretion of cAMP in PHP was able to explain the hitherto unknown pathogenesis of this disorder: the parathyroid hormone -- sensitive adenylcyclase system is here unable to mediate the action of parathyroid hormone on its target cells, so causing a peripheral block of parathyroid-hormone activity. Therefore GREENBERG and coworkers justly term PHP a disease of the second messenger.", "contents": "[Investigations of the urinary cAMP-excretion in pseudohypoparathyroidism (author's transl)]. Pseudohypoparathyroidism (PHP) is a hereditary disorder with typical dysmorphic signs and clinical and laboratory symptoms of hypoparathyroidism which is resistant however to parathyroid extract. ALBRIGHT and coworkers supposed that this resistance was caused by an inability of the renal tubules to respond to parathyroid hormone. On three children, suffering from PHP, we could demonstrate that parathyroid extract-resistance disappears during treatment with vitamin D. Measurements of urinary excretion of cAMP, the second messenger for parathyroid hormone, in the same patients showed low basal levels of this nucleotide, which could not be stimulated by parathyroid extract either before or during vitamin D-treatment. This constantly low and by parathyroid extract not stimulable cAMP-excretion is now the symptom with the most diagnostic value for PHP. Beyond this the finding of this defective urinary excretion of cAMP in PHP was able to explain the hitherto unknown pathogenesis of this disorder: the parathyroid hormone -- sensitive adenylcyclase system is here unable to mediate the action of parathyroid hormone on its target cells, so causing a peripheral block of parathyroid-hormone activity. Therefore GREENBERG and coworkers justly term PHP a disease of the second messenger."}
{"id": "PMID:199876", "title": "Isolation of polioviruses from paralyzed  children in the province of Isfahan, Iran.", "content": "Viral studies were carried out in 47 children with clinical features of paralytic poliomyelitis. Forty-seven healthy children matched in age and sex were used as controls. Fourteen cases of polioviruses were isolated from the paralyzed children. Of these, 10 isolates were of type one, 2 type two and 2 type three. Among the healthy children two polioviruses were isolated, one type 1 and one type three. The importance of vaccination against poliomyelitis is emphasized.", "contents": "Isolation of polioviruses from paralyzed  children in the province of Isfahan, Iran. Viral studies were carried out in 47 children with clinical features of paralytic poliomyelitis. Forty-seven healthy children matched in age and sex were used as controls. Fourteen cases of polioviruses were isolated from the paralyzed children. Of these, 10 isolates were of type one, 2 type two and 2 type three. Among the healthy children two polioviruses were isolated, one type 1 and one type three. The importance of vaccination against poliomyelitis is emphasized."}
{"id": "PMID:199879", "title": "The action of collagenase on K-type Bence-Jones proteins.", "content": "The proteolytic action of a bacterial collagenase on two Bence-Jones k chains has been studied and the localization of the cleavage sites accomplished. The implications of this enzymatic attack are discussed.", "contents": "The action of collagenase on K-type Bence-Jones proteins. The proteolytic action of a bacterial collagenase on two Bence-Jones k chains has been studied and the localization of the cleavage sites accomplished. The implications of this enzymatic attack are discussed."}
{"id": "PMID:199885", "title": "Transient effects of norepinephrine on myocardial oxygen balance.", "content": "In conscious dogs with experimental atrioventricular block and with ventricles paced at constant rate the effects of norepinephrine (NE) and isoproterenol (ISO) on coronary flow, coronary resistance, and myocardial O2-balance were investigated. Myocardial O2-S balance, as estimated from continuous measurement of coronary venous O2-S saturation, was used for the discrimination of coronary dilation induced either directly by vascular beta-adrenoreceptor stimulation or indirectly by increased myocardial metabolism. Following bolus injection of NE (0.3 microgram/kg) or ISO (0.1 microgram/kg) into the pulmonary artery, coronary venous O2-S saturation increased from a control of 25 +/- 2% O2-S saturation (mean +/- S.D.) transiently to 51 +/- 5 and 62 +/- 5% O2-S saturation respectively. After beta1-adrenoreceptor blockade these increases were reduced to 33 +/- 4 and 41 +/- 3% O2-S saturation, respectively. The remaining increase after NE was abolished when atropine was given in addition to beta1-b blockade. After beta1 + 2-adrenoreceptor blockade neither NE nor ISO injection had an effect on coronary venous O2 saturation. After beta1-b blockade was superimposed on ganglionic blockade NE injection led to a decrease in coronary venous O2-S saturation indicating a latent alpha-a activity of NE. NE seems to act directly via beta1-a adrenoreceptors, since no differences were observed in the time courses of changes in coronary venous O2-S saturation after left atrial injection of NE when compared to adenosine. It is concluded that circulating NE like ISO is able to improve myocardial oxygen balance by a direct vasodilating effect on canine coronary vessels mediated by vascular beta1-adrenoreceptors.", "contents": "Transient effects of norepinephrine on myocardial oxygen balance. In conscious dogs with experimental atrioventricular block and with ventricles paced at constant rate the effects of norepinephrine (NE) and isoproterenol (ISO) on coronary flow, coronary resistance, and myocardial O2-balance were investigated. Myocardial O2-S balance, as estimated from continuous measurement of coronary venous O2-S saturation, was used for the discrimination of coronary dilation induced either directly by vascular beta-adrenoreceptor stimulation or indirectly by increased myocardial metabolism. Following bolus injection of NE (0.3 microgram/kg) or ISO (0.1 microgram/kg) into the pulmonary artery, coronary venous O2-S saturation increased from a control of 25 +/- 2% O2-S saturation (mean +/- S.D.) transiently to 51 +/- 5 and 62 +/- 5% O2-S saturation respectively. After beta1-adrenoreceptor blockade these increases were reduced to 33 +/- 4 and 41 +/- 3% O2-S saturation, respectively. The remaining increase after NE was abolished when atropine was given in addition to beta1-b blockade. After beta1 + 2-adrenoreceptor blockade neither NE nor ISO injection had an effect on coronary venous O2 saturation. After beta1-b blockade was superimposed on ganglionic blockade NE injection led to a decrease in coronary venous O2-S saturation indicating a latent alpha-a activity of NE. NE seems to act directly via beta1-a adrenoreceptors, since no differences were observed in the time courses of changes in coronary venous O2-S saturation after left atrial injection of NE when compared to adenosine. It is concluded that circulating NE like ISO is able to improve myocardial oxygen balance by a direct vasodilating effect on canine coronary vessels mediated by vascular beta1-adrenoreceptors."}
{"id": "PMID:199889", "title": "[Multiplication of murine C-type viruses in mouse teratocarcinoma cell lines].", "content": "The host-virus interactions of several murine C type viruses with cell lines established in vitro from a mouse teratocarcinoma were studied. The cells used in this study were the multipotential stem cells, or embryonal carcinoma cells, and the differentiated cells derived from a same tumor.", "contents": "[Multiplication of murine C-type viruses in mouse teratocarcinoma cell lines]. The host-virus interactions of several murine C type viruses with cell lines established in vitro from a mouse teratocarcinoma were studied. The cells used in this study were the multipotential stem cells, or embryonal carcinoma cells, and the differentiated cells derived from a same tumor."}
{"id": "PMID:199893", "title": "Hypothalamic-pituitary function tests: current status.", "content": "Pituitary disorders can be diagnosed more readily and precisely as a result of two recent advances: development of radioimmunoassays for direct measurement of each pituitary hormone in blood, and availability of hypothalamic hormones for use in provocative tests for secretion of thyroid-stimulating hormone, prolactin, and gonadotropic hormones.", "contents": "Hypothalamic-pituitary function tests: current status. Pituitary disorders can be diagnosed more readily and precisely as a result of two recent advances: development of radioimmunoassays for direct measurement of each pituitary hormone in blood, and availability of hypothalamic hormones for use in provocative tests for secretion of thyroid-stimulating hormone, prolactin, and gonadotropic hormones."}
{"id": "PMID:199895", "title": "Van Buchem disease.", "content": "Van Buchem disease is a hereditary sclerosing dysplasia of bone. Both dominant and autosomal recessive modes of transmission have been described. The dominant form tends to be a benign disorder and symptoms are usually confined to those associated with the enlargement of the jaw. The recessive forms tend to have a greater morbidity and symptoms arise from pressure on cranial nerves by hyperostotic bone at the base of the skull. Patients of the dominant families have often had a torus palatinus. No haematological changes are found. The alkaline phosphatase may be raised--even if the total level is not elevated, the bone fraction may be increased. The radiological appearances are regarded as characteristic. The jaw is enlarged and thickened to an extent not seen in other bone dysplasias such as osteopetrosis. The cortices of the diaphyses are thickened and the medullary cavities are encroached upon but not obliterated. Abnormal modelling of the bone ends is not found in van Buchem disease. In long bones the distribution is predominantly diaphyseal but the bone ends are also affected.", "contents": "Van Buchem disease. Van Buchem disease is a hereditary sclerosing dysplasia of bone. Both dominant and autosomal recessive modes of transmission have been described. The dominant form tends to be a benign disorder and symptoms are usually confined to those associated with the enlargement of the jaw. The recessive forms tend to have a greater morbidity and symptoms arise from pressure on cranial nerves by hyperostotic bone at the base of the skull. Patients of the dominant families have often had a torus palatinus. No haematological changes are found. The alkaline phosphatase may be raised--even if the total level is not elevated, the bone fraction may be increased. The radiological appearances are regarded as characteristic. The jaw is enlarged and thickened to an extent not seen in other bone dysplasias such as osteopetrosis. The cortices of the diaphyses are thickened and the medullary cavities are encroached upon but not obliterated. Abnormal modelling of the bone ends is not found in van Buchem disease. In long bones the distribution is predominantly diaphyseal but the bone ends are also affected."}
{"id": "PMID:199896", "title": "[The significance of the local oxygen pressure and of the PO2 histogram for the evaluation of the state of oxygen supply to various organs (author's transl)].", "content": "Theoretical and experimental investigations have shown that the oxygen pressure field of an organ reflects the state of the oxygen supply of a tissue. Unfortunately it is practically impossible to measure the total oxygen pressure field. Meaurements of arterial and venous PO2 or of the mean tissue PO2 do not reveal the local tissue situation. Measurements together with K. Kunze and M. Kessler lead us to the conclusion, that the oxygen pressure field can be characterized sufficiently well by a PO2-histogram. Under normal conditions the PO2-histogram is bell shaped with a steeper left side. The form and position is rather consistent. In hypoxia low PO2 values increase causing a leftward shift of the histogram; in hyperoxia the bell shaped form is destroyed and the form becomes broader and irregular. The form of the histogram gives also information about the state of the regulation of the microflow. It can be measured by PO2 microelectrodes as well as by multiwire surface electrodes. Both techniques have been applied successfully with patients.", "contents": "[The significance of the local oxygen pressure and of the PO2 histogram for the evaluation of the state of oxygen supply to various organs (author's transl)]. Theoretical and experimental investigations have shown that the oxygen pressure field of an organ reflects the state of the oxygen supply of a tissue. Unfortunately it is practically impossible to measure the total oxygen pressure field. Meaurements of arterial and venous PO2 or of the mean tissue PO2 do not reveal the local tissue situation. Measurements together with K. Kunze and M. Kessler lead us to the conclusion, that the oxygen pressure field can be characterized sufficiently well by a PO2-histogram. Under normal conditions the PO2-histogram is bell shaped with a steeper left side. The form and position is rather consistent. In hypoxia low PO2 values increase causing a leftward shift of the histogram; in hyperoxia the bell shaped form is destroyed and the form becomes broader and irregular. The form of the histogram gives also information about the state of the regulation of the microflow. It can be measured by PO2 microelectrodes as well as by multiwire surface electrodes. Both techniques have been applied successfully with patients."}
{"id": "PMID:199901", "title": "Collagenase-released non-collagenous proteins of cortical bone matrix.", "content": "Two distinct groups of non-collagenous components were isolated from rat cortical bone gelatin which had previously been digested with purified bacterial collagenase. One component was disulfide-bonded, strongly acidic, trypsin-labile glycoprotein aggregate with a molecular mass of more than 100,000 daltons. When reduced with beta-mercaptoethanol this protein disaggregated into subunits with a molecular mass of about 60,000 daltons. The other components consisted of a group of polypeptides with a molecular mass of about 5,000 daltons. The latter group was present in collagenase digests prepared from normal bone gelatin but was hardly detectable or absent in digests of gelatin prepared from either autolyzed, trypsinized or lathyritic bone, or from the residue of neutral salt extracted rat tail tendon.", "contents": "Collagenase-released non-collagenous proteins of cortical bone matrix. Two distinct groups of non-collagenous components were isolated from rat cortical bone gelatin which had previously been digested with purified bacterial collagenase. One component was disulfide-bonded, strongly acidic, trypsin-labile glycoprotein aggregate with a molecular mass of more than 100,000 daltons. When reduced with beta-mercaptoethanol this protein disaggregated into subunits with a molecular mass of about 60,000 daltons. The other components consisted of a group of polypeptides with a molecular mass of about 5,000 daltons. The latter group was present in collagenase digests prepared from normal bone gelatin but was hardly detectable or absent in digests of gelatin prepared from either autolyzed, trypsinized or lathyritic bone, or from the residue of neutral salt extracted rat tail tendon."}
{"id": "PMID:199902", "title": "A modified method for the preparation of agarose.", "content": "A simple procedure for the preparation of agarose suitable for electrophoresis is developed in which anionic polysaccharides are removed by extracting the agar gel-granules with phosphate buffer (0.03 M, pH 6.8) containing urea (4 M), followed by electrophoresis in the same buffer system. Further, alkali treatment in the presence of sodium borohydride, eliminates electroendosmosis, giving essentially a neutral agarose, as judged by the electrophoretic behaviour of basic substances like crystal violet and cytochrome C. The purified agarose with yields 60-65%, has a sulphur content less than 0.1%, and forms rigid, transparent gels.", "contents": "A modified method for the preparation of agarose. A simple procedure for the preparation of agarose suitable for electrophoresis is developed in which anionic polysaccharides are removed by extracting the agar gel-granules with phosphate buffer (0.03 M, pH 6.8) containing urea (4 M), followed by electrophoresis in the same buffer system. Further, alkali treatment in the presence of sodium borohydride, eliminates electroendosmosis, giving essentially a neutral agarose, as judged by the electrophoretic behaviour of basic substances like crystal violet and cytochrome C. The purified agarose with yields 60-65%, has a sulphur content less than 0.1%, and forms rigid, transparent gels."}
{"id": "PMID:199903", "title": "[Influence of methylcobalamin and cyanocobalamin on the neoplastic process in rats].", "content": "The effect of methylcobalamine (5.6-dimethylbenzimidazolyl-Co-methylcobamide, CH3-B12) and cyanocobalamine (5,6-dimethylbenzimidazolyly-Co-cyanocobamide, CN-B12) on the growth of Walker's carcinosarcoma and longevity of white noninbred rats with implanted Zajdela ascites hepatoma was studied. The two agents exerted a similar effect. They 1) reduced the survival of rats with implanted Zajdela ascites hepatoma and Walker's carcinosarcoma; 2) did not increase the cell concentration in ascites; and 3) increased the total volume of ascites.", "contents": "[Influence of methylcobalamin and cyanocobalamin on the neoplastic process in rats]. The effect of methylcobalamine (5.6-dimethylbenzimidazolyl-Co-methylcobamide, CH3-B12) and cyanocobalamine (5,6-dimethylbenzimidazolyly-Co-cyanocobamide, CN-B12) on the growth of Walker's carcinosarcoma and longevity of white noninbred rats with implanted Zajdela ascites hepatoma was studied. The two agents exerted a similar effect. They 1) reduced the survival of rats with implanted Zajdela ascites hepatoma and Walker's carcinosarcoma; 2) did not increase the cell concentration in ascites; and 3) increased the total volume of ascites."}
{"id": "PMID:199909", "title": "Mechanisms of amitriptyline induced hypothermia in the rat.", "content": "Effects of amitriptyline on rectal temperature of male rats were studied at the ambient temperature of 25 degrees C. Drugs were administered intraperitoneally. Amitryptyline elicited a dose related hypothermia. The hypothermia was attenuated by phenoxybenzamine 10 mg/kg, haloperidol 2 mg/kg, diphenhydramine 5 mg/kg, atropine 20 mg/kg, and cyproheptadine 5 mg/kg. Propranolol, at a dose of 5 mg/kg, had no effect on the hypothermia. Theophylline 50 mg/kg and dibutyryl cyclic AMP 20 mg/kg inhibited the hypothermia produced by anitriptyline. Pretreatment with parachloroamphetamine (PCA), 2 or 5 mg/kg daily for 3 days, strongly antagonized the hypothermia. In addition, pretreatment with parachlorophenylalanine (PCPA), 100 mg/kg daily for three days, reduced the brain 5-hydroxytryptamine (5-HT) concentration to 20% of the control level and completely blocked the hypothermia response. When brain 5-HT concentration recovered to 50% of the control level in PCPA treated rats following the administration of 10 mg/kg 5-hydroxytryptophan (5-HTP) the hypothermia induced by amitriptyline was restored. However, the administration of 5-HT, 5 mg/kg, to PCPA treated rats did not increase brain 5-HT concentration or restore the amitriptyline induced hypothermia (AIH). Results suggest that amitriptyline interacts with several transmitter substances to produce hypothermia. Since the ability of amitriptyline to produce hypothermia was correlated with brain 5-HT content, 5-HT might play an important role in the mediation of AIH.", "contents": "Mechanisms of amitriptyline induced hypothermia in the rat. Effects of amitriptyline on rectal temperature of male rats were studied at the ambient temperature of 25 degrees C. Drugs were administered intraperitoneally. Amitryptyline elicited a dose related hypothermia. The hypothermia was attenuated by phenoxybenzamine 10 mg/kg, haloperidol 2 mg/kg, diphenhydramine 5 mg/kg, atropine 20 mg/kg, and cyproheptadine 5 mg/kg. Propranolol, at a dose of 5 mg/kg, had no effect on the hypothermia. Theophylline 50 mg/kg and dibutyryl cyclic AMP 20 mg/kg inhibited the hypothermia produced by anitriptyline. Pretreatment with parachloroamphetamine (PCA), 2 or 5 mg/kg daily for 3 days, strongly antagonized the hypothermia. In addition, pretreatment with parachlorophenylalanine (PCPA), 100 mg/kg daily for three days, reduced the brain 5-hydroxytryptamine (5-HT) concentration to 20% of the control level and completely blocked the hypothermia response. When brain 5-HT concentration recovered to 50% of the control level in PCPA treated rats following the administration of 10 mg/kg 5-hydroxytryptophan (5-HTP) the hypothermia induced by amitriptyline was restored. However, the administration of 5-HT, 5 mg/kg, to PCPA treated rats did not increase brain 5-HT concentration or restore the amitriptyline induced hypothermia (AIH). Results suggest that amitriptyline interacts with several transmitter substances to produce hypothermia. Since the ability of amitriptyline to produce hypothermia was correlated with brain 5-HT content, 5-HT might play an important role in the mediation of AIH."}
{"id": "PMID:199910", "title": "Role played by the adenylcyclase-cAMP system of the rat septal area on Na+, K+ and water renal excretion.", "content": "In this study, the participation of the adenylcyclase--cAMP system of the rat septal area in the mediation of the natriuretic, kaliuretic and diuretic effects of noradrenaline (NA) was investigated. The intraseptal injection of 20 nmol of NA caused a significant increase in the urinary excretion of Na+ and K+ as well as in the urinary volume during the 2 hr period following the intracerebral injection which was blocked by 40 nmol of phentolamine, locally injected, 30 min before the catecholamine. In contrast, pretreatment with propranolol (100 nmol) potentiated the effects of NA on salt and water renal excretion. The intraseptal injection of 3.12 to 50 nmol of dibutryrl cyclic adenosine monophosphate (db cAMP) caused dose-dependent increase in natriuresis and kaliuresis, but a decrease in urinary volume. Under the same experimental conditions, caffeine administration (6.25 to 100 nmol) also induced dose-dependent increases in Na+ and K+ urinary output. These results indicate that the saluretic effect of NA may be mediated by an alpha receptor-induced activation of the adenylcyclase--cAMP system in the septal area.", "contents": "Role played by the adenylcyclase-cAMP system of the rat septal area on Na+, K+ and water renal excretion. In this study, the participation of the adenylcyclase--cAMP system of the rat septal area in the mediation of the natriuretic, kaliuretic and diuretic effects of noradrenaline (NA) was investigated. The intraseptal injection of 20 nmol of NA caused a significant increase in the urinary excretion of Na+ and K+ as well as in the urinary volume during the 2 hr period following the intracerebral injection which was blocked by 40 nmol of phentolamine, locally injected, 30 min before the catecholamine. In contrast, pretreatment with propranolol (100 nmol) potentiated the effects of NA on salt and water renal excretion. The intraseptal injection of 3.12 to 50 nmol of dibutryrl cyclic adenosine monophosphate (db cAMP) caused dose-dependent increase in natriuresis and kaliuresis, but a decrease in urinary volume. Under the same experimental conditions, caffeine administration (6.25 to 100 nmol) also induced dose-dependent increases in Na+ and K+ urinary output. These results indicate that the saluretic effect of NA may be mediated by an alpha receptor-induced activation of the adenylcyclase--cAMP system in the septal area."}
{"id": "PMID:199911", "title": "Actinomycin D peritonitis in rats: a tool for the study of early events in inflammation.", "content": "The injection of 50 microgram i.p. of actinomycin D produces, in rats, a biphasic inflammatory reaction. The first short lasting phase (approximately 24 h) is characterized by the decrease of the peritoneal cells number, by the increase of the levels of both cAMP and cGMP in the peritoneal cells and by the increased synthesis and release of lysosomal enzymes from these cells. The second long lasting phase (greater than 120 h) is characterized by the exudate formation, intense cellular immigration, continuous release of lysosomal enzymes, return to or below the normal values of the intracellular levels of cyclic nucleotides. The treatment of rats with a steroidal drug reduces the beta-glucuronidase release and, concomitantly, the intracellular cyclic nucleotides levels. Indomethacin is ineffective.", "contents": "Actinomycin D peritonitis in rats: a tool for the study of early events in inflammation. The injection of 50 microgram i.p. of actinomycin D produces, in rats, a biphasic inflammatory reaction. The first short lasting phase (approximately 24 h) is characterized by the decrease of the peritoneal cells number, by the increase of the levels of both cAMP and cGMP in the peritoneal cells and by the increased synthesis and release of lysosomal enzymes from these cells. The second long lasting phase (greater than 120 h) is characterized by the exudate formation, intense cellular immigration, continuous release of lysosomal enzymes, return to or below the normal values of the intracellular levels of cyclic nucleotides. The treatment of rats with a steroidal drug reduces the beta-glucuronidase release and, concomitantly, the intracellular cyclic nucleotides levels. Indomethacin is ineffective."}
{"id": "PMID:199912", "title": "Role of brain monoamines in the anticonvulsant effect of imipramine in albino rats.", "content": "The role of brain monoamines in the anticonvulsant effect of imipramine was investigated in albino rats, against maximal electroshock-induced seizures, by using drugs with well-defined effects on brain monoamines. The results suggest a definite role for noradrenaline in imipramine anticonvulsant action. Dopamine and 5-hydroxytryptamine do not appear to be involved in this effect of imipramine.", "contents": "Role of brain monoamines in the anticonvulsant effect of imipramine in albino rats. The role of brain monoamines in the anticonvulsant effect of imipramine was investigated in albino rats, against maximal electroshock-induced seizures, by using drugs with well-defined effects on brain monoamines. The results suggest a definite role for noradrenaline in imipramine anticonvulsant action. Dopamine and 5-hydroxytryptamine do not appear to be involved in this effect of imipramine."}
{"id": "PMID:199913", "title": "Voluntary ethanol drinking by the RAT: effects of 2-aminoethylisothiouronium Salt, a modifier of NAD:NADH and norelegnine, a beta-carboline derivative.", "content": "Voluntary intake of ethanol solution (ETOH) was decreased in rats administered 2-aminoethylisothiouronium bromide hydrobromide (AET), an agent reported to alter NAD:NADH ratios in rat liver. Repeated administration of same dose of AET to ETOH-naive rats produced a significant inhibition of liver aldehyde dehydrogenase. Ethanol intake was decreased in rats given noreleagnine (NLG), a beta-carbone derivative reported to inhibit monoamine oxidase. Repeated administration of NLG exerted a significant inhibitory effect on liver alcohol dehydrogenase activity. It is concluded that the observed reduction of ethanol under AET which inhibits liver aldehyde dehydrogenase may reflect an antabuse-like reaction and the reduction of ethanol intake under NLG may be due, in part, to a build-up of alcohol in the blood and brain through inhibition of ethanol metabolism. The results are discussed in reference to the possible mechanism of action underlying voluntary intake of ethanol in rats, implicating alteration of NAD:NADH ratios in the biochemical processes underlying alcohol intake of rats.", "contents": "Voluntary ethanol drinking by the RAT: effects of 2-aminoethylisothiouronium Salt, a modifier of NAD:NADH and norelegnine, a beta-carboline derivative. Voluntary intake of ethanol solution (ETOH) was decreased in rats administered 2-aminoethylisothiouronium bromide hydrobromide (AET), an agent reported to alter NAD:NADH ratios in rat liver. Repeated administration of same dose of AET to ETOH-naive rats produced a significant inhibition of liver aldehyde dehydrogenase. Ethanol intake was decreased in rats given noreleagnine (NLG), a beta-carbone derivative reported to inhibit monoamine oxidase. Repeated administration of NLG exerted a significant inhibitory effect on liver alcohol dehydrogenase activity. It is concluded that the observed reduction of ethanol under AET which inhibits liver aldehyde dehydrogenase may reflect an antabuse-like reaction and the reduction of ethanol intake under NLG may be due, in part, to a build-up of alcohol in the blood and brain through inhibition of ethanol metabolism. The results are discussed in reference to the possible mechanism of action underlying voluntary intake of ethanol in rats, implicating alteration of NAD:NADH ratios in the biochemical processes underlying alcohol intake of rats."}
{"id": "PMID:199915", "title": "Angiographic diagnosis of endocrine tumors of the pancreas.", "content": "The angiographic findings in 18 patients with endocrine tumors of the pancreas are analyzed. A literature review (262 cases) is performed in order to assess the accuracy of angiography in diagnosing islet cell tumors, in particular multiple and small (less than 1 cm) lesions. Problems of differential diagnosis of pancreatic and extrapancreatic structures and lesions are discussed.", "contents": "Angiographic diagnosis of endocrine tumors of the pancreas. The angiographic findings in 18 patients with endocrine tumors of the pancreas are analyzed. A literature review (262 cases) is performed in order to assess the accuracy of angiography in diagnosing islet cell tumors, in particular multiple and small (less than 1 cm) lesions. Problems of differential diagnosis of pancreatic and extrapancreatic structures and lesions are discussed."}
{"id": "PMID:199914", "title": "Hormonal influences on RNA and DNA synthesis in developing rat brain.", "content": "In recent years, authors' interest was focussed on the role of hormones in the brain biochemical maturation during the early postnatal life. One-day-old rats were used in the investigation of the following hormones: thyroxine (T4), hydrocortisone, aldosterone and ACTH, in unique or repeated administration. Dynamics of cerebral RNA and DNA synthesis, a realiable indicator of central nervous system (CNS) maturation, was investigated. Authors' research led to the following conclusions: In infant rats, cerebral RNA and DNA synthesis exhibits a continuous increase, with a peak between 7 and 14 days after birth. Hydrocortisone induces a significant inhibition of cerebral RNA and DNA synthesis, more important in 7-day-old rats. In ACTH-treated newborn rats, RNA and DNA synthesis presents a high stimulation in 7- and 14-day-old rats. Aldosterone elicits an enhancement of brain nucleic acid synthesis, more marked in 7- and 14-day-old rats. Thyroxine administration induces a marked stimulation of cerebral RNA and DNA synthesis, greatest at 7 and 14 days after birth. The results confirm the important, even decisive, role of endocrine secretions during the early postnatal life, as far as the subsequent individual development is concerned.", "contents": "Hormonal influences on RNA and DNA synthesis in developing rat brain. In recent years, authors' interest was focussed on the role of hormones in the brain biochemical maturation during the early postnatal life. One-day-old rats were used in the investigation of the following hormones: thyroxine (T4), hydrocortisone, aldosterone and ACTH, in unique or repeated administration. Dynamics of cerebral RNA and DNA synthesis, a realiable indicator of central nervous system (CNS) maturation, was investigated. Authors' research led to the following conclusions: In infant rats, cerebral RNA and DNA synthesis exhibits a continuous increase, with a peak between 7 and 14 days after birth. Hydrocortisone induces a significant inhibition of cerebral RNA and DNA synthesis, more important in 7-day-old rats. In ACTH-treated newborn rats, RNA and DNA synthesis presents a high stimulation in 7- and 14-day-old rats. Aldosterone elicits an enhancement of brain nucleic acid synthesis, more marked in 7- and 14-day-old rats. Thyroxine administration induces a marked stimulation of cerebral RNA and DNA synthesis, greatest at 7 and 14 days after birth. The results confirm the important, even decisive, role of endocrine secretions during the early postnatal life, as far as the subsequent individual development is concerned."}
{"id": "PMID:199922", "title": "Activation of cAMP-dependent protein kinase without a corresponding increase in phosphorylase activity.", "content": "The effect of prostaglandin E1(PGE1) and epinephrine on glycogen metabolism has been investigated in the perfused rat heart. Both agents produced increases in cAMP and the cAMP-dependent protein kinase activity ratio. When dosages were adjusted to give equal increases in the protein kinase activity ratio from a basal value of 0.15 to as high as 0.40, only epinephrine caused a significant increase in phosphorylase activity. When used together, PGE1 did not effect the ability of epinephrine to increase phosphorylase activity.", "contents": "Activation of cAMP-dependent protein kinase without a corresponding increase in phosphorylase activity. The effect of prostaglandin E1(PGE1) and epinephrine on glycogen metabolism has been investigated in the perfused rat heart. Both agents produced increases in cAMP and the cAMP-dependent protein kinase activity ratio. When dosages were adjusted to give equal increases in the protein kinase activity ratio from a basal value of 0.15 to as high as 0.40, only epinephrine caused a significant increase in phosphorylase activity. When used together, PGE1 did not effect the ability of epinephrine to increase phosphorylase activity."}
{"id": "PMID:199923", "title": "Enhanced affinity of opiate receptors for naloxone in striatal slices of morphine-dependent mice.", "content": "Slices of corpus striatum were allowed to accumulate 3H-morphine and then they were placed in a small chamber and superfused with Krebs-Ringer bicarbonate solution. 100 to 1 pM of naloxone caused an immediate increase in the release of morphine from the slices when it was placed in the superfusion fluid at 0, 5 or 15 min after the the start of the superfusion. Slices from morphine-dependent mice were more sensitive to the naloxone-induced release of morphine than those of control mice. The data suggest that the affinity of the opiate receptors in the corpus straitum for naloxone is increased in morphine-dependent mice.", "contents": "Enhanced affinity of opiate receptors for naloxone in striatal slices of morphine-dependent mice. Slices of corpus striatum were allowed to accumulate 3H-morphine and then they were placed in a small chamber and superfused with Krebs-Ringer bicarbonate solution. 100 to 1 pM of naloxone caused an immediate increase in the release of morphine from the slices when it was placed in the superfusion fluid at 0, 5 or 15 min after the the start of the superfusion. Slices from morphine-dependent mice were more sensitive to the naloxone-induced release of morphine than those of control mice. The data suggest that the affinity of the opiate receptors in the corpus straitum for naloxone is increased in morphine-dependent mice."}
{"id": "PMID:199924", "title": "Cyclic AMP and cyclic GMP levels in glandular stomach of restrained rats.", "content": "Cyclic AMP and cyclic GMP were measured in glandular stomach of rats subjected to saline administration, cold (4 degrees C), restraint and restraint+cold after 15, 30, 60, 90 and 120 minutes. All animals subjected to restraint+cold had gastric ulceration after 2 hours. A significant but transient decrease in cAMP was observed 15 minutes after restraint+cold. A marked, sustained and significant decrease of cGMP was observed in the same group of animals. It is concluded that it seems unlikely to be a correlation between cAMP and cGMP changes of the stomach and the restraint-induced gastric ulceration.", "contents": "Cyclic AMP and cyclic GMP levels in glandular stomach of restrained rats. Cyclic AMP and cyclic GMP were measured in glandular stomach of rats subjected to saline administration, cold (4 degrees C), restraint and restraint+cold after 15, 30, 60, 90 and 120 minutes. All animals subjected to restraint+cold had gastric ulceration after 2 hours. A significant but transient decrease in cAMP was observed 15 minutes after restraint+cold. A marked, sustained and significant decrease of cGMP was observed in the same group of animals. It is concluded that it seems unlikely to be a correlation between cAMP and cGMP changes of the stomach and the restraint-induced gastric ulceration."}
{"id": "PMID:199936", "title": "[Bifocal bronchial granulocellular myoblastoma (Abrikosov's tumor)].", "content": "To the 44 observations of endobronchial granular cell myoblastoma described in the world literature can be added the case of a 52-year-old patient who presented with bifocal localization of this rare tumor of enigmatic origin. The two tumors were isolated from each other, one being situated at the level of the bronchus of the left superior lobe without implantation on the main bronchus, and the other at the bifurcation of the anterior segmental bronchus and left apico-dorsal segmental bronchus. The irreversible chronic-inflammatory peripheral lesions necessitated pneumonectomy. The patient is in excellent health 17 years after pneumonectomy. This is the fifth case of bifocal bronchial granular cell myoblastoma to be published.", "contents": "[Bifocal bronchial granulocellular myoblastoma (Abrikosov's tumor)]. To the 44 observations of endobronchial granular cell myoblastoma described in the world literature can be added the case of a 52-year-old patient who presented with bifocal localization of this rare tumor of enigmatic origin. The two tumors were isolated from each other, one being situated at the level of the bronchus of the left superior lobe without implantation on the main bronchus, and the other at the bifurcation of the anterior segmental bronchus and left apico-dorsal segmental bronchus. The irreversible chronic-inflammatory peripheral lesions necessitated pneumonectomy. The patient is in excellent health 17 years after pneumonectomy. This is the fifth case of bifocal bronchial granular cell myoblastoma to be published."}
{"id": "PMID:199937", "title": "[Serum lipids in diminished kidney function, during hemodialysis and after kidney transplantation].", "content": "Lipids have been investigated in three groups of patients with chronic renal insufficiency. 19 patients were on conservative treatment (no dialysis), 52 patients were on regular hemodialysis, and 27 patients had been transplanted. The results were compared with those obtained from control subjects of the same age and sex. Hyperlipoproteinemia was found in 25% of the uremic patients, 55% of hemodialysis patients, and 85% of transplant recipients. The predominant lipid abnormalities were hyperlipoproteinemia of Type IV in both uremic (5 out of 19) and hemodialysis patients (17 ou of 52). Hyperlipoproteinemia of Type II was mainly observed after transplantation (IIb: 13, IIa: 5 out of 27).", "contents": "[Serum lipids in diminished kidney function, during hemodialysis and after kidney transplantation]. Lipids have been investigated in three groups of patients with chronic renal insufficiency. 19 patients were on conservative treatment (no dialysis), 52 patients were on regular hemodialysis, and 27 patients had been transplanted. The results were compared with those obtained from control subjects of the same age and sex. Hyperlipoproteinemia was found in 25% of the uremic patients, 55% of hemodialysis patients, and 85% of transplant recipients. The predominant lipid abnormalities were hyperlipoproteinemia of Type IV in both uremic (5 out of 19) and hemodialysis patients (17 ou of 52). Hyperlipoproteinemia of Type II was mainly observed after transplantation (IIb: 13, IIa: 5 out of 27)."}
{"id": "PMID:199938", "title": "[Antiviral activity in the serum of patients with acute myelocytic leukemia: prognostic significance. Preliminary report].", "content": "In view of suggestions that acute myeloblastic leukemia (AML) may be of viral etiology, sera of 31 patients suffering from AML were investigated for antiviral activity. Fowl plague virus (FPV), vesicular stomatitis virus (VSV), BT 20 mammary carcinoma cells and chicken embryo fibroblasts (CEF) were used as assay systems. In the FPV-BT20 system, 19 of 20 patients whose blood sample was taken when they were in complete remission showed antiviral activity in their sera. These patients stayed in complete remission for at least three months after the blood sample was taken. In the sera of 11 patients no antiviral activity could be found with the FPV-BT20 assay system. 3 of the 11 were in relapse, 5 had a relapse within 3 months and 3 stayed in remission more than 3 months after the blood sample was taken. In the FPV-CEF and in the VSV-BT20 system antiviral activity was also found. The activity in the FPV-CEF system corresponded well with the FPV-BT20 assay and the disease status, whereas the activity detected by the VSV-BT20 system did not. The nature of the antiviral activities in the sera of AML patients against FPV and VSV is not yet clear. Interferon and specific antiviral antibodies can probably be ruled out. The antiviral activity against FPV appears to be a biological index of the activity of the disease and might eventually be used to determine intensity and length of treatment.", "contents": "[Antiviral activity in the serum of patients with acute myelocytic leukemia: prognostic significance. Preliminary report]. In view of suggestions that acute myeloblastic leukemia (AML) may be of viral etiology, sera of 31 patients suffering from AML were investigated for antiviral activity. Fowl plague virus (FPV), vesicular stomatitis virus (VSV), BT 20 mammary carcinoma cells and chicken embryo fibroblasts (CEF) were used as assay systems. In the FPV-BT20 system, 19 of 20 patients whose blood sample was taken when they were in complete remission showed antiviral activity in their sera. These patients stayed in complete remission for at least three months after the blood sample was taken. In the sera of 11 patients no antiviral activity could be found with the FPV-BT20 assay system. 3 of the 11 were in relapse, 5 had a relapse within 3 months and 3 stayed in remission more than 3 months after the blood sample was taken. In the FPV-CEF and in the VSV-BT20 system antiviral activity was also found. The activity in the FPV-CEF system corresponded well with the FPV-BT20 assay and the disease status, whereas the activity detected by the VSV-BT20 system did not. The nature of the antiviral activities in the sera of AML patients against FPV and VSV is not yet clear. Interferon and specific antiviral antibodies can probably be ruled out. The antiviral activity against FPV appears to be a biological index of the activity of the disease and might eventually be used to determine intensity and length of treatment."}
{"id": "PMID:199939", "title": "[Hereditary myeloperoxidase deficiency. Clinical, biological and genetic study].", "content": "A case is reported of hereditary myeloperoxidase deficiency in a diabetic patient suffering from a Candida albicans hepatic abscess. Myeloperoxidase (MPO) is completely absent from the neutrophils and monocytes, although it is present in the eosinophils. Functional granulocyte studies have revealed normalchemotactic and phagocytic activity, although the bacterial activity is partially diminished with regard to Staphylococcus aureus and is almost nil with regard to Candida albicans. The granulocytic metabolism, when stimulated by zymosan, is characterized by greatly increased oxygen consumption. Genetic investigations have been conducted in 28 members of the patient's family. Cyto- and biochemical determination of MPO is clearly diminished in close relatives of the patient. Genetic analysis indicates recessive autosomal transmission with variable expressivity of the gene for the heterozygote state.", "contents": "[Hereditary myeloperoxidase deficiency. Clinical, biological and genetic study]. A case is reported of hereditary myeloperoxidase deficiency in a diabetic patient suffering from a Candida albicans hepatic abscess. Myeloperoxidase (MPO) is completely absent from the neutrophils and monocytes, although it is present in the eosinophils. Functional granulocyte studies have revealed normalchemotactic and phagocytic activity, although the bacterial activity is partially diminished with regard to Staphylococcus aureus and is almost nil with regard to Candida albicans. The granulocytic metabolism, when stimulated by zymosan, is characterized by greatly increased oxygen consumption. Genetic investigations have been conducted in 28 members of the patient's family. Cyto- and biochemical determination of MPO is clearly diminished in close relatives of the patient. Genetic analysis indicates recessive autosomal transmission with variable expressivity of the gene for the heterozygote state."}
{"id": "PMID:199933", "title": "Somatotrophic, thyrotrophic and adrenocorticotrophic functions of the anterior pituitary in obesity.", "content": "The basal plasma level of GH, TSH and ACTH and the reserve capacities of the adenohypophysis in the secretion of these hormones was investigated radioimmunologically in 80 patients with excessive weight (from 15.3% to 180.0%) and a group of healthy subjects. It is shown that obesity is accompanied by diverse changes of the anterior pituitary GH, TSH and ACTH functions, which may be explained by their varied participation in the fatty metabolism. The pituitary somatotrophic function is weakened in obese subjects and its disorders advance with increase of the grade of obesity. Reduced pituitary thyrotrophic function in obesity causes weakening of thyroid function; disorders of the thyroid regulation occur at the hypothalamic level. The increased blood plasma concentration of ACTH in obese subjects has a compensatory character. The reserve capacities of the adrenocorticotrophic function of the pituitary are diminished in obestiy. Disturbances of the anterior pituitary GH, TSH and ACTH functions show a single-direction character both in alimentary-constitutional and in hypothalamic obesity.", "contents": "Somatotrophic, thyrotrophic and adrenocorticotrophic functions of the anterior pituitary in obesity. The basal plasma level of GH, TSH and ACTH and the reserve capacities of the adenohypophysis in the secretion of these hormones was investigated radioimmunologically in 80 patients with excessive weight (from 15.3% to 180.0%) and a group of healthy subjects. It is shown that obesity is accompanied by diverse changes of the anterior pituitary GH, TSH and ACTH functions, which may be explained by their varied participation in the fatty metabolism. The pituitary somatotrophic function is weakened in obese subjects and its disorders advance with increase of the grade of obesity. Reduced pituitary thyrotrophic function in obesity causes weakening of thyroid function; disorders of the thyroid regulation occur at the hypothalamic level. The increased blood plasma concentration of ACTH in obese subjects has a compensatory character. The reserve capacities of the adrenocorticotrophic function of the pituitary are diminished in obestiy. Disturbances of the anterior pituitary GH, TSH and ACTH functions show a single-direction character both in alimentary-constitutional and in hypothalamic obesity."}
{"id": "PMID:199940", "title": "[Selection of patients with breast cancer with regard to endocrine therapy].", "content": "Predictive tests assisting in selection of breast cancer patients for endocrine therapy have been reviewed. Information gained from histologic sections, such as degree of the tumor differentiation, degree of elastosis, Barr-body count and the DNA content, are valuable predictors of prognosis and response to endocrine therapy. The length of time between mastectomy and recurrence of metastasis is an important factor in predicting response to ablative endocrine surgery. The presence of various enzymes in the tumor tissue, blood groups, immunologic competence, altered metabolism of tryptophan, urinary excretion of steroids and  in vitro hormonal responsiveness of the tumor tissue have not been widely used as predictors of tumor response to endocrine therapy. The determination of hormone receptors in primary or metastatic breast tumors is at present the most reliable test in selecting breast cancer  patients for endocrine therapy. Future developments in hormone receptor assay may provide a means of tailoring endocrine therapy to the individual patient.", "contents": "[Selection of patients with breast cancer with regard to endocrine therapy]. Predictive tests assisting in selection of breast cancer patients for endocrine therapy have been reviewed. Information gained from histologic sections, such as degree of the tumor differentiation, degree of elastosis, Barr-body count and the DNA content, are valuable predictors of prognosis and response to endocrine therapy. The length of time between mastectomy and recurrence of metastasis is an important factor in predicting response to ablative endocrine surgery. The presence of various enzymes in the tumor tissue, blood groups, immunologic competence, altered metabolism of tryptophan, urinary excretion of steroids and  in vitro hormonal responsiveness of the tumor tissue have not been widely used as predictors of tumor response to endocrine therapy. The determination of hormone receptors in primary or metastatic breast tumors is at present the most reliable test in selecting breast cancer  patients for endocrine therapy. Future developments in hormone receptor assay may provide a means of tailoring endocrine therapy to the individual patient."}
{"id": "PMID:199941", "title": "Pituitary nuclear 3,5,3'-triiodothyronine and thyrotropin secretion: an explanation for the effect of thyroxine.", "content": "An excellent correlation was observed between nuclear triiodothyronine (T3) and the ensuing suppression of thyrotropin (TSH) after a single intravenous injection of T3 to thyroidectomized (hypothyroid) rats. At 1 and 2 hours after injection of thyroxine (T4), in amounts equally potent to the administered T3 in terms of acute suppression of TSH, the same quantities of T3 were found in the pituitary nuclei. Virtually no nuclear T4 was present, and plasma T3 was negligible at these short intervals after T4 injection. These results suggest that suppression of TSH release in hypothyroid rats occurs by interaction of T3 with the nuclear receptor of the thyrotroph. After T4 injection, the T3 found in the nucleus is derived from rapid intrapituitary monodeiodination.", "contents": "Pituitary nuclear 3,5,3'-triiodothyronine and thyrotropin secretion: an explanation for the effect of thyroxine. An excellent correlation was observed between nuclear triiodothyronine (T3) and the ensuing suppression of thyrotropin (TSH) after a single intravenous injection of T3 to thyroidectomized (hypothyroid) rats. At 1 and 2 hours after injection of thyroxine (T4), in amounts equally potent to the administered T3 in terms of acute suppression of TSH, the same quantities of T3 were found in the pituitary nuclei. Virtually no nuclear T4 was present, and plasma T3 was negligible at these short intervals after T4 injection. These results suggest that suppression of TSH release in hypothyroid rats occurs by interaction of T3 with the nuclear receptor of the thyrotroph. After T4 injection, the T3 found in the nucleus is derived from rapid intrapituitary monodeiodination."}
{"id": "PMID:199942", "title": "Stereospecific and nonstereospecific effects of (+)- and (-)-morphine: evidence for a new class of receptors?", "content": "The unnatural (+) enantiomer of morphine had minimal activity in three opiate assays in vitro: the rat brain homogenate binding assay, the electrically stimulated guinea pig ileum assay, and the inhibition of adenylate cyclase in neuroblastoma X glioma hybrid cell homogenates. When (+)-morphine was microinfected into the periaqueductal gray (a site known to mediate morphine analgesia) of drug-naive rats, there was only minimal analgesia, but the hyperresponsivity usually observed after microinfection of (-)-morphine occurred. Also, when (+)-morphine was microinfected into the midbrain reticular formation of drug-naive rats, rotation similar to that following microinjection of (-)-morphine occurred. These behaviors were not blocked by naloxone. Significantly, they typically occur in precipitated abstinence in morphine-dependent rats. These observations suggest that there are at least two classes of receptors, one stereospecific and blocked by naloxone and the other only weakly stereospecific and not blocked by naloxone, and that precipitated abstinence may be due, in part, to a selective blockade of receptors of the former class but not of the latter.", "contents": "Stereospecific and nonstereospecific effects of (+)- and (-)-morphine: evidence for a new class of receptors? The unnatural (+) enantiomer of morphine had minimal activity in three opiate assays in vitro: the rat brain homogenate binding assay, the electrically stimulated guinea pig ileum assay, and the inhibition of adenylate cyclase in neuroblastoma X glioma hybrid cell homogenates. When (+)-morphine was microinfected into the periaqueductal gray (a site known to mediate morphine analgesia) of drug-naive rats, there was only minimal analgesia, but the hyperresponsivity usually observed after microinfection of (-)-morphine occurred. Also, when (+)-morphine was microinfected into the midbrain reticular formation of drug-naive rats, rotation similar to that following microinjection of (-)-morphine occurred. These behaviors were not blocked by naloxone. Significantly, they typically occur in precipitated abstinence in morphine-dependent rats. These observations suggest that there are at least two classes of receptors, one stereospecific and blocked by naloxone and the other only weakly stereospecific and not blocked by naloxone, and that precipitated abstinence may be due, in part, to a selective blockade of receptors of the former class but not of the latter."}
{"id": "PMID:199943", "title": "Cyclic nucleotides injected intracellularly into rat superior cervical ganglion cells.", "content": "Intracellular iontophoresis of either adenosine 3',5'-monophosphate or guanosine 3',5'-monophosphate produces a membrane depolarization and an increased membrane conductance in sympathetic ganglion cells of the rat superior cervical ganglion. Since adenosine 3',5'-monophosphate did not cause a membrane hyperpolarization, it is difficult to assign it a second messenger role in the mediation of the slow inhibitory postsynaptic potential. However, these results do not rule out the possibility that the cyclic nucleotides, at the intracellular concentrations attained in these experiments, participate in cellular processes that contribute to conductance changes which result in depolarization of the ganglion cell membrane.", "contents": "Cyclic nucleotides injected intracellularly into rat superior cervical ganglion cells. Intracellular iontophoresis of either adenosine 3',5'-monophosphate or guanosine 3',5'-monophosphate produces a membrane depolarization and an increased membrane conductance in sympathetic ganglion cells of the rat superior cervical ganglion. Since adenosine 3',5'-monophosphate did not cause a membrane hyperpolarization, it is difficult to assign it a second messenger role in the mediation of the slow inhibitory postsynaptic potential. However, these results do not rule out the possibility that the cyclic nucleotides, at the intracellular concentrations attained in these experiments, participate in cellular processes that contribute to conductance changes which result in depolarization of the ganglion cell membrane."}
{"id": "PMID:199944", "title": "Coagulation abnormalities in liver disease.", "content": "The decreased capacity of the liver to synthesize proteins is the main cause of decreased blood levels of clotting factors II, V, VII, IX, X and of antithrombin III in patients with liver disease. Therefore, determination of the activity or concentration of these coagulation proteins is a useful test of liver function and guide to prognosis, provided that other mechanisms which may influence the blood level are carefully considered. Clotting factor assays have an only limited value for the differential diagnosis in liver disease.", "contents": "Coagulation abnormalities in liver disease. The decreased capacity of the liver to synthesize proteins is the main cause of decreased blood levels of clotting factors II, V, VII, IX, X and of antithrombin III in patients with liver disease. Therefore, determination of the activity or concentration of these coagulation proteins is a useful test of liver function and guide to prognosis, provided that other mechanisms which may influence the blood level are carefully considered. Clotting factor assays have an only limited value for the differential diagnosis in liver disease."}
{"id": "PMID:199946", "title": "Primary Epstein-Barr virus infection in a renal transplant recipient.", "content": "A young girl with familial nephronophthisis and chronic renal failure contracted a primary Epstein-Barr virus infection after renal transplantation. During the illness she developed a clinical picture of fever and pneumonitis which closely resembled the posttransplantation syndrome usually associated with cytomegalovirus, although she had no evidence of cytomegalovirus infection. A younger sibling with the same renal disease was found retrospectively to have apparently had an earlier subclinical Epstein-Barr virus infection.", "contents": "Primary Epstein-Barr virus infection in a renal transplant recipient. A young girl with familial nephronophthisis and chronic renal failure contracted a primary Epstein-Barr virus infection after renal transplantation. During the illness she developed a clinical picture of fever and pneumonitis which closely resembled the posttransplantation syndrome usually associated with cytomegalovirus, although she had no evidence of cytomegalovirus infection. A younger sibling with the same renal disease was found retrospectively to have apparently had an earlier subclinical Epstein-Barr virus infection."}
{"id": "PMID:199947", "title": "Vibrometry and uremic peripheral neuropathy.", "content": "The vibratory sensation threshold (VST) was measured with a vibrometer to assess the progression of neuropathy in patients with end-stage renal disease. Normal patients and patients receiving chronic hemodialysis were studied. We found that the longer the patients were dialyzed, the lower their VST (P less than 0.01). Regression equations were established to predict threshold values versus age of both groups, and VST versus months on dialysis in the patient population. Vibrometry was an important addition to the assessment of peripheral neuropathy in our dialysis patients. It offers low cost, little patient preparation, and requires little professional time for examination and interpretation.", "contents": "Vibrometry and uremic peripheral neuropathy. The vibratory sensation threshold (VST) was measured with a vibrometer to assess the progression of neuropathy in patients with end-stage renal disease. Normal patients and patients receiving chronic hemodialysis were studied. We found that the longer the patients were dialyzed, the lower their VST (P less than 0.01). Regression equations were established to predict threshold values versus age of both groups, and VST versus months on dialysis in the patient population. Vibrometry was an important addition to the assessment of peripheral neuropathy in our dialysis patients. It offers low cost, little patient preparation, and requires little professional time for examination and interpretation."}
{"id": "PMID:199948", "title": "Review of 18 years' experience with pituitary tumors.", "content": "The presenting signs, symptoms, roentgenographic findings, endocrine evaluations, treatment, and results in 68 cases of presumed pituitary adenomas treated over an 18-year period are discussed. The most common symptoms were headache, acromegalic changes, visual symptoms, and amenorrhea. Most common physical findings were obesity, acromegaly, and visual field defects, usually bitemporal hemianopsia. Roentgenographic evidence of sellar erosion was almost universal but angiography and pneumoencephalography were required to evaluate suprasellar extension. Brain scan was not considered a particularly useful diagnostic tool. Endocrine status was best evaluated by a battery of tests including 17-OH, 17-KS, T3, T4, PBI, ACTH stimulation, and FSH and STH levels. (Prolactin levels are currently being obtained, also). Surgical specimens were obtained in 29 patients, with subsequent diagnoses of 22 chromophobe adenomas, five eosinophilie adenomas, one cystic adenoma, and one necrotic tumor. All five eosinophilic tumors came from acromegalic patients. Patients treated by operation alone or operation followed by radiotherapy generally had less \"medical morbidity\" than did patients who received radiotherapy alone.", "contents": "Review of 18 years' experience with pituitary tumors. The presenting signs, symptoms, roentgenographic findings, endocrine evaluations, treatment, and results in 68 cases of presumed pituitary adenomas treated over an 18-year period are discussed. The most common symptoms were headache, acromegalic changes, visual symptoms, and amenorrhea. Most common physical findings were obesity, acromegaly, and visual field defects, usually bitemporal hemianopsia. Roentgenographic evidence of sellar erosion was almost universal but angiography and pneumoencephalography were required to evaluate suprasellar extension. Brain scan was not considered a particularly useful diagnostic tool. Endocrine status was best evaluated by a battery of tests including 17-OH, 17-KS, T3, T4, PBI, ACTH stimulation, and FSH and STH levels. (Prolactin levels are currently being obtained, also). Surgical specimens were obtained in 29 patients, with subsequent diagnoses of 22 chromophobe adenomas, five eosinophilie adenomas, one cystic adenoma, and one necrotic tumor. All five eosinophilic tumors came from acromegalic patients. Patients treated by operation alone or operation followed by radiotherapy generally had less \"medical morbidity\" than did patients who received radiotherapy alone."}
{"id": "PMID:199949", "title": "The absence of antagonism between extracts of Clinacanthus nutans Burm. and Naja naja siamensis venom.", "content": "Clinacanthus nutans Burm, a herb reputed in Thailand and Malaysia to be \"snakebite antidote\" has been tested in vitro and in vivo for antivenin activity. The aqueous extract of C. nutans leaves has been found to have no effect on the inhibition of neuromuscular transmission produced by purified Naja naja siamensis neurotoxin in isolated rat phrenic-nerve diaphragm preparations. The extract of C. nutans, when given orally or intraperitoneally, are ineffective in prolonging the survival time of experimental mice receiving lethal doses of N.n. siamensis crude venom. Oral administrations of the herb extracts pretreated with alpha-amylase or beta-amylase also fail to protect the animal. It is concluded that the extract of C. nutans can not antagonize the action of cobra venom.", "contents": "The absence of antagonism between extracts of Clinacanthus nutans Burm. and Naja naja siamensis venom. Clinacanthus nutans Burm, a herb reputed in Thailand and Malaysia to be \"snakebite antidote\" has been tested in vitro and in vivo for antivenin activity. The aqueous extract of C. nutans leaves has been found to have no effect on the inhibition of neuromuscular transmission produced by purified Naja naja siamensis neurotoxin in isolated rat phrenic-nerve diaphragm preparations. The extract of C. nutans, when given orally or intraperitoneally, are ineffective in prolonging the survival time of experimental mice receiving lethal doses of N.n. siamensis crude venom. Oral administrations of the herb extracts pretreated with alpha-amylase or beta-amylase also fail to protect the animal. It is concluded that the extract of C. nutans can not antagonize the action of cobra venom."}
{"id": "PMID:199952", "title": "Genetics of the mammalian phenylalanine hydroxylase system: I. Isolation of phenylalanine hydroxylase-deficient tyrosine auxotrophs from rat hepatoma cells.", "content": "Cultured rat hepatoma cells, H4-II-E-C3, are known to possess a phenylananine hydroxylating system which is sufficient to enable them to grow in tyrosine-depleted medium. Using standard procedures of auxotroph enrichment with this cell line, we have isolated tyrosine auxotrophs for the first time. We report in this paper the class of auxotrophs with (a) reduced (15-64% of wild type) or (b) absent activity of phenylalanine hydroxylase, an enzymic component of the phenylalanine hydroxylating system. This class of auxotroph presumably contains either lower (a) [or zero (b)] levels of normal phenylalanine hydroxylase protein than wild type, or mutant phenylalanine hydroxylase protein with lowered (or zero) activity. The two subgroups of auxotrophs (a) and (b) differ from each other in their revertibility and their growth behavior in the tyrosine-free medium. Over a 12-month period of testing, the auxotrophs have been highly stable with respect to their phenylalanine hydroxylase activity and growth phenotype in tyrosine-free medium. Such auxotrophs should facilitate genetic and biochemical study of the genes controlling the phenylalanine hydroxylation system and the study of phenylketonuria.", "contents": "Genetics of the mammalian phenylalanine hydroxylase system: I. Isolation of phenylalanine hydroxylase-deficient tyrosine auxotrophs from rat hepatoma cells. Cultured rat hepatoma cells, H4-II-E-C3, are known to possess a phenylananine hydroxylating system which is sufficient to enable them to grow in tyrosine-depleted medium. Using standard procedures of auxotroph enrichment with this cell line, we have isolated tyrosine auxotrophs for the first time. We report in this paper the class of auxotrophs with (a) reduced (15-64% of wild type) or (b) absent activity of phenylalanine hydroxylase, an enzymic component of the phenylalanine hydroxylating system. This class of auxotroph presumably contains either lower (a) [or zero (b)] levels of normal phenylalanine hydroxylase protein than wild type, or mutant phenylalanine hydroxylase protein with lowered (or zero) activity. The two subgroups of auxotrophs (a) and (b) differ from each other in their revertibility and their growth behavior in the tyrosine-free medium. Over a 12-month period of testing, the auxotrophs have been highly stable with respect to their phenylalanine hydroxylase activity and growth phenotype in tyrosine-free medium. Such auxotrophs should facilitate genetic and biochemical study of the genes controlling the phenylalanine hydroxylation system and the study of phenylketonuria."}
{"id": "PMID:199953", "title": "Increased polyethylene glycol-mediated fusion competence in mitotic cells of a mouse lymphoid cell line.", "content": "Spontaneous mitotic cells of the mouse leukemic cell line GF7 are preferentially included in cell fusion products after treatment with polyethylene glycol (PEG). This implies a unique configuration of the natural mitotic membrane which is particularly vulnerable to induction of fusion by PEG. Colcemid-arrested GF7 mitotic cells, however, are excluded from PEG-induced cell fusion products, suggesting that colcemid reverses the membrane configuration which is susceptible to the action of PEG. When Sendai virus is used as the fusogenic agent, both colcemid-arrested and spontaneous mitotic cells are selectively fused. There must, therefore, be an essential membrane-fusogen reaction which is characteristically different for each of these agents.", "contents": "Increased polyethylene glycol-mediated fusion competence in mitotic cells of a mouse lymphoid cell line. Spontaneous mitotic cells of the mouse leukemic cell line GF7 are preferentially included in cell fusion products after treatment with polyethylene glycol (PEG). This implies a unique configuration of the natural mitotic membrane which is particularly vulnerable to induction of fusion by PEG. Colcemid-arrested GF7 mitotic cells, however, are excluded from PEG-induced cell fusion products, suggesting that colcemid reverses the membrane configuration which is susceptible to the action of PEG. When Sendai virus is used as the fusogenic agent, both colcemid-arrested and spontaneous mitotic cells are selectively fused. There must, therefore, be an essential membrane-fusogen reaction which is characteristically different for each of these agents."}
{"id": "PMID:199954", "title": "The control of cell proliferation by preformed purines: a genetic study. I. Isolation and preliminary characterization of Chinese hamster lines with single or multiple defects in purine \"salvage\" pathways.", "content": "Sublines with single or multiple defects in purine \"salvage\" enzymes were isolated from the Chinese hamster fibroblastic line GMA32 through single or successive one-step selections for resistance to purine analogs. They were examined for their ability to incorporate purine bases and nucleosides into macromolecules, for their sensitivity to growth inhibitory purines, and for their rescue by exogenous purines from deprivation imposed by metabolic inhibitors of endogenous synthesis. The results show that a deficiency of either adenosine kinase (EC 2.7.1.20), adenine phosphoribosyltransferase (EC 2.4.2.7) or hypoxanthine guanine phosphoribosyltransferase (EC 2.4.2.8) abolishes the ability of adenine to cause cell death by interfering with pyrimidine synthesis; on the other hand, the pyrimidine starvation caused by adenosine is fully prevented only by a deficiency of adenosine kinase.", "contents": "The control of cell proliferation by preformed purines: a genetic study. I. Isolation and preliminary characterization of Chinese hamster lines with single or multiple defects in purine \"salvage\" pathways. Sublines with single or multiple defects in purine \"salvage\" enzymes were isolated from the Chinese hamster fibroblastic line GMA32 through single or successive one-step selections for resistance to purine analogs. They were examined for their ability to incorporate purine bases and nucleosides into macromolecules, for their sensitivity to growth inhibitory purines, and for their rescue by exogenous purines from deprivation imposed by metabolic inhibitors of endogenous synthesis. The results show that a deficiency of either adenosine kinase (EC 2.7.1.20), adenine phosphoribosyltransferase (EC 2.4.2.7) or hypoxanthine guanine phosphoribosyltransferase (EC 2.4.2.8) abolishes the ability of adenine to cause cell death by interfering with pyrimidine synthesis; on the other hand, the pyrimidine starvation caused by adenosine is fully prevented only by a deficiency of adenosine kinase."}
{"id": "PMID:199955", "title": "Extracranial metastases of glioblastoma multiforme confirmed by electron microscopy.", "content": "A case of glioblastoma multiforme which metastasized to the pleura and the lymph nodes of the neck is described. The metastases were detected during the life of the patient. The glial nature of the metastases was confirmed by electronmicriscopic demonstration of typical 90-100 angstrom wide glial fibrils occupying the tumor cell cytoplasm. Electronmicroscopy is recommended to prove the astrocytic nature of a metastatic glioblastoma multiforme. A review of the literature of histologically documented extracranial metastases of glioblastoma multiforme reveals an increase in frequency in recent years. Increased efforts at detection and documentation or an increase in occurrence caused by new methods of treatment are the two possible explanations for this trend.", "contents": "Extracranial metastases of glioblastoma multiforme confirmed by electron microscopy. A case of glioblastoma multiforme which metastasized to the pleura and the lymph nodes of the neck is described. The metastases were detected during the life of the patient. The glial nature of the metastases was confirmed by electronmicriscopic demonstration of typical 90-100 angstrom wide glial fibrils occupying the tumor cell cytoplasm. Electronmicroscopy is recommended to prove the astrocytic nature of a metastatic glioblastoma multiforme. A review of the literature of histologically documented extracranial metastases of glioblastoma multiforme reveals an increase in frequency in recent years. Increased efforts at detection and documentation or an increase in occurrence caused by new methods of treatment are the two possible explanations for this trend."}
{"id": "PMID:199956", "title": "Clinical characteristics of the lethal cytomegalovirus infection following renal transplantation.", "content": "An ongoing prospective study of the role of viruses in renal transplant recipients has provided identification of two patterns of cytomegalovirus (CMV) infection.  In both patterns, fever and leukopenia occur within 6 months after transplant. In addition, the benign form is characterized by renal biopsy evidence of rejection and brisk Antibody responses to CMV. The lethal syndrome runs a typical 4 week course, beginning with prostration, orthostatic hypotension, mild hypoxemia and progressing to severe pulmonary and hepatic dysfunction, muscle wasting, central nervous system depression, and death. antibody responses to CMV are minimal, and renal biopsy does not show rejection despite elevation of serum creatinine. At autopsy, CMV is found in lung, liver, kidney, gastrointestinal tract, and brain. Successful management of the potentially lethal kidney, gastrointestinal tract, and brain.  Successful management of the potentially lethal CMV syndrome requires rapid clinical recognition and immediate reduction of immunosuppressive therapy. future prospects for control include development of a CMV vaccine and specific antiviral chemotherapy.", "contents": "Clinical characteristics of the lethal cytomegalovirus infection following renal transplantation. An ongoing prospective study of the role of viruses in renal transplant recipients has provided identification of two patterns of cytomegalovirus (CMV) infection.  In both patterns, fever and leukopenia occur within 6 months after transplant. In addition, the benign form is characterized by renal biopsy evidence of rejection and brisk Antibody responses to CMV. The lethal syndrome runs a typical 4 week course, beginning with prostration, orthostatic hypotension, mild hypoxemia and progressing to severe pulmonary and hepatic dysfunction, muscle wasting, central nervous system depression, and death. antibody responses to CMV are minimal, and renal biopsy does not show rejection despite elevation of serum creatinine. At autopsy, CMV is found in lung, liver, kidney, gastrointestinal tract, and brain. Successful management of the potentially lethal kidney, gastrointestinal tract, and brain.  Successful management of the potentially lethal CMV syndrome requires rapid clinical recognition and immediate reduction of immunosuppressive therapy. future prospects for control include development of a CMV vaccine and specific antiviral chemotherapy."}
{"id": "PMID:199957", "title": "Regional hyperplastic lymph nodes in breast cancer: the role of lymphocytes and nodal macrophages. An immunological study with a five-year follow-up.", "content": "Five stage I and stage II breast cancer patients with sinus histiocytosis in two or more enlarged regional lymph nodes were studied. Peripheral lymphocytes, serum, and nodal lymphocytes were tested in vitro for cytotoxicity against autologous normal and tumor cells. Nodal macrophages were incubated with autologous peripheral lymphocytes and these \"activated\" lymphocytes then were tested in vitro for cytotoxicity against autologous normal and tumor cells. Peripheral lymphocytes (L) were not cytotoxic to autologous tumor (T) cells at 25:1 L/T ratios. Nodal lymphocytes were specifically cytotoxic to autologous tumor cells. Macrophages from hyperplastic regional lymph nodes transferred tumor specific inmunity to peripheral lymphocytes. Macrophages from small, nonhyperplastic regional lymph nodes did not transfer tumor specific immunity. With the advent of adjuvant chemotherapy and its attack on systemic immunity, a quantitative, immunopathological classification of breast cancer patients is needed in order to properly select patients for further therapy.", "contents": "Regional hyperplastic lymph nodes in breast cancer: the role of lymphocytes and nodal macrophages. An immunological study with a five-year follow-up. Five stage I and stage II breast cancer patients with sinus histiocytosis in two or more enlarged regional lymph nodes were studied. Peripheral lymphocytes, serum, and nodal lymphocytes were tested in vitro for cytotoxicity against autologous normal and tumor cells. Nodal macrophages were incubated with autologous peripheral lymphocytes and these \"activated\" lymphocytes then were tested in vitro for cytotoxicity against autologous normal and tumor cells. Peripheral lymphocytes (L) were not cytotoxic to autologous tumor (T) cells at 25:1 L/T ratios. Nodal lymphocytes were specifically cytotoxic to autologous tumor cells. Macrophages from hyperplastic regional lymph nodes transferred tumor specific inmunity to peripheral lymphocytes. Macrophages from small, nonhyperplastic regional lymph nodes did not transfer tumor specific immunity. With the advent of adjuvant chemotherapy and its attack on systemic immunity, a quantitative, immunopathological classification of breast cancer patients is needed in order to properly select patients for further therapy."}
{"id": "PMID:199958", "title": "Evolution of surgical treatment of bilateral Wilms' tumor.", "content": "Bilateral Wilms' tumor (stage V) accounts for 10 to 15% of patients with nephroblastoma. Heretofore, surgical resection in many of these children presented insoluble technical problems. Ex vivo renal perfusion with \"bench\" surgical excision and revascularization has been applied in the management of a child with bilateral Wilms' tumor unresectable by conventional techniques. Complete extirpation of tumor was accomplished. Furthermore, the autotransplanted kidney was removed from the field of radiation therapy given after operation. By selective application of this technique, the child with bilateral Wilms's tumor can be approached with a greater expectation of cure.", "contents": "Evolution of surgical treatment of bilateral Wilms' tumor. Bilateral Wilms' tumor (stage V) accounts for 10 to 15% of patients with nephroblastoma. Heretofore, surgical resection in many of these children presented insoluble technical problems. Ex vivo renal perfusion with \"bench\" surgical excision and revascularization has been applied in the management of a child with bilateral Wilms' tumor unresectable by conventional techniques. Complete extirpation of tumor was accomplished. Furthermore, the autotransplanted kidney was removed from the field of radiation therapy given after operation. By selective application of this technique, the child with bilateral Wilms's tumor can be approached with a greater expectation of cure."}
{"id": "PMID:199961", "title": "[The immunity against challenge with swine fever virus of piglets from sows vaccinated with C-strain virus (author's transl)].", "content": "The protective value of maternal antibodies against exposure by contact to virulent swine fever virus was investigated in a group of 40 piglets at the age of 33-40 days. The piglets were from a single farm and derived from 10 sows which had been vaccinated once with C-strain virus 5.5 months before farrowing. Four contact controls of approximately the same age as the test-groups and born from non-vaccinated sows died 4-10 days (av. 7.5 days) after the onset of symptoms. Three pigs from the group under test succombed to swine fever after an illness of 12 to 16 days (av. 14 days) and one animal died from coli-enteritis. A febrile reaction (av. duration 2.9 days) was observed in more than 75% of the piglets that survived the challenge and all survivors showed a serological response. There was no relationship between the serum-neutralisation titer before challenge and the presence or absence of fever. Attempts to isolate swine fever virus by means of leucoyte cultures, bonemarrow cultures and plasma clot cultures from tonsils, spleen and lymphnodes of surviving piglets 5-7 weeks after the start of the experiment were not successful. It is concluded that a high proportion of the piglets born from dams vaccinated with C-strain virus are protected against contact exposure till the age that they can successfully be vaccinated themselves.", "contents": "[The immunity against challenge with swine fever virus of piglets from sows vaccinated with C-strain virus (author's transl)]. The protective value of maternal antibodies against exposure by contact to virulent swine fever virus was investigated in a group of 40 piglets at the age of 33-40 days. The piglets were from a single farm and derived from 10 sows which had been vaccinated once with C-strain virus 5.5 months before farrowing. Four contact controls of approximately the same age as the test-groups and born from non-vaccinated sows died 4-10 days (av. 7.5 days) after the onset of symptoms. Three pigs from the group under test succombed to swine fever after an illness of 12 to 16 days (av. 14 days) and one animal died from coli-enteritis. A febrile reaction (av. duration 2.9 days) was observed in more than 75% of the piglets that survived the challenge and all survivors showed a serological response. There was no relationship between the serum-neutralisation titer before challenge and the presence or absence of fever. Attempts to isolate swine fever virus by means of leucoyte cultures, bonemarrow cultures and plasma clot cultures from tonsils, spleen and lymphnodes of surviving piglets 5-7 weeks after the start of the experiment were not successful. It is concluded that a high proportion of the piglets born from dams vaccinated with C-strain virus are protected against contact exposure till the age that they can successfully be vaccinated themselves."}
{"id": "PMID:199962", "title": "Molecular composition of lecithins in the primary hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene.", "content": "The lecithins of the primary hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene (DAB) and host liver of rat were isolated, and the individual molecular species were estimated quantitatively by combined thin-layer and gaschromatographic analysis and specific enzymic hydrolysis. The DAB-hepatoma lecithins appeared to have more specific positioning of fatty acids than the transplanted hepatoma lecithins which have been reported by Dyatlovitskaya et al. (1974). However, there were some striking differences to be noted between the DAB-hepatoma and host liver lecithins. The usual type of molecular species of lecithin, saturated-unsaturated species, was the main component in the hepatoma and host liver. The amounts of the unusual species having impaired positional specificity in fatty acid such as the saturated-saturated and the unsaturated-saturated species were high in the DAB-hepatoma when compared with host liver, although the content of the unsaturated-unsaturated species of lecithin were almost similar in both the tissues. The formation of the unusual species of lecithin in tumor tissues was discussed in relation to the impairing in the enzyme systems involved in lecithin synthesis.", "contents": "Molecular composition of lecithins in the primary hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene. The lecithins of the primary hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene (DAB) and host liver of rat were isolated, and the individual molecular species were estimated quantitatively by combined thin-layer and gaschromatographic analysis and specific enzymic hydrolysis. The DAB-hepatoma lecithins appeared to have more specific positioning of fatty acids than the transplanted hepatoma lecithins which have been reported by Dyatlovitskaya et al. (1974). However, there were some striking differences to be noted between the DAB-hepatoma and host liver lecithins. The usual type of molecular species of lecithin, saturated-unsaturated species, was the main component in the hepatoma and host liver. The amounts of the unusual species having impaired positional specificity in fatty acid such as the saturated-saturated and the unsaturated-saturated species were high in the DAB-hepatoma when compared with host liver, although the content of the unsaturated-unsaturated species of lecithin were almost similar in both the tissues. The formation of the unusual species of lecithin in tumor tissues was discussed in relation to the impairing in the enzyme systems involved in lecithin synthesis."}
{"id": "PMID:199963", "title": "Immunological and biochemical investigations on the fluorocarbon-treated antigens obtained from placenta and from cancer tissues.", "content": "Biochemical and immunological investigations were made on the nature of fluorocarbon-treated antigens obtained from placenta and cancer tissues. 1) By the diffusion in gel method, a specific antigen common to cancer tissues was found in placental tissue, but not in normal tissue. Immunoelectrophoretically, a characteristic precipitate line was found in alpha2-globulin region. 2) Further purification of the placental antigens was carried out by DEAE-cellulose chromatography. Four fractions positive to Folin reaction were detected. 3) Immunoelectrophoresis revealed that the active component was concentrated in a fraction eluted with 0.1 M NaCl in 0.05 M phosphate buffer, pH 5.8 (5.8-fraction). 4) Further purification of the active component was performed by using polyacrylamide gel electrophoresis. Chemical analysis indicated that it belonged to glycoprotein. 5) This substance did not induce anemia in rabbits and had no influence on the osmotic fragility of erythrocytes. These results indicate that this substance is different from the anemia-inducing substance which was previously reported by us.", "contents": "Immunological and biochemical investigations on the fluorocarbon-treated antigens obtained from placenta and from cancer tissues. Biochemical and immunological investigations were made on the nature of fluorocarbon-treated antigens obtained from placenta and cancer tissues. 1) By the diffusion in gel method, a specific antigen common to cancer tissues was found in placental tissue, but not in normal tissue. Immunoelectrophoretically, a characteristic precipitate line was found in alpha2-globulin region. 2) Further purification of the placental antigens was carried out by DEAE-cellulose chromatography. Four fractions positive to Folin reaction were detected. 3) Immunoelectrophoresis revealed that the active component was concentrated in a fraction eluted with 0.1 M NaCl in 0.05 M phosphate buffer, pH 5.8 (5.8-fraction). 4) Further purification of the active component was performed by using polyacrylamide gel electrophoresis. Chemical analysis indicated that it belonged to glycoprotein. 5) This substance did not induce anemia in rabbits and had no influence on the osmotic fragility of erythrocytes. These results indicate that this substance is different from the anemia-inducing substance which was previously reported by us."}
{"id": "PMID:199964", "title": "alpha-L-Iduronidase activity in established lymphoblastoid cells from patients with Hurler and Scheie syndromes transformed by Epstein-Barr virus.", "content": "alpha-L-Iduronidase activity was determined in established lymphoblastoid cells, which were transformed in vitro by Epstein-Barr virus, of lymphocytes-rich cell populations isolated from peripheral blood of patients with Hurler and Scheie syndromes. alpha-L-Iduronidase activities in established lymphoblastoid cells from patients were undetectable, while activities of control subjects were clearly detected. These results suggest that established lymphoblastoid cells are useful for the enzymatic study of genetic mucopolysaccharidoses.", "contents": "alpha-L-Iduronidase activity in established lymphoblastoid cells from patients with Hurler and Scheie syndromes transformed by Epstein-Barr virus. alpha-L-Iduronidase activity was determined in established lymphoblastoid cells, which were transformed in vitro by Epstein-Barr virus, of lymphocytes-rich cell populations isolated from peripheral blood of patients with Hurler and Scheie syndromes. alpha-L-Iduronidase activities in established lymphoblastoid cells from patients were undetectable, while activities of control subjects were clearly detected. These results suggest that established lymphoblastoid cells are useful for the enzymatic study of genetic mucopolysaccharidoses."}
{"id": "PMID:199968", "title": "[Change in the hybridization characteristics of rapidly-labelled ribonucleic acids during tumor \"progression\"].", "content": "The hybridization properties of in vivo rapidly labeled with 14C-orotate both nuclear and mitochondrial ribonucleic acids from the MD hepatoma were investigated. During tumour progression the repression of nuclear genome found at its early stages (5th to 6th passages) is replaced by the increase of hybridizability of nuclear DNA with a population of 14C-RNA's as well as by the appearance of new classes of pulse labeled RNA's. In other words, at late stages of tumour progression (60th passage) there occur a de-repression of nuclear genome. The hybridizability of mitochondrial RNA with nuclear DNA remains almost the same at different tumour progression stages. The results obtained are discussed in the light of literature data available.", "contents": "[Change in the hybridization characteristics of rapidly-labelled ribonucleic acids during tumor \"progression\"]. The hybridization properties of in vivo rapidly labeled with 14C-orotate both nuclear and mitochondrial ribonucleic acids from the MD hepatoma were investigated. During tumour progression the repression of nuclear genome found at its early stages (5th to 6th passages) is replaced by the increase of hybridizability of nuclear DNA with a population of 14C-RNA's as well as by the appearance of new classes of pulse labeled RNA's. In other words, at late stages of tumour progression (60th passage) there occur a de-repression of nuclear genome. The hybridizability of mitochondrial RNA with nuclear DNA remains almost the same at different tumour progression stages. The results obtained are discussed in the light of literature data available."}
{"id": "PMID:199969", "title": "[Analysis of substances released from Zajdela ascites hepatoma cells exposed to UV radiation of different wavelengths. III. Release of nucleoproteins and carbohydrates].", "content": "Irradiation of the Zaidela ascite hepatoma cells with physiological doses of shortwave length (254 nm) and longwave length (300-380 nm) UV light (far and near UV radiation) is accompanied by the release of ribonucleoproteins (RNP) from the cells, whose amounts increase with dose. Irradiation with far and near UV light leads to the release of high-molecular and low-molecular RNP, respectively. No deoxyribonucleoprotein were found among the released substances. Non-protein fractions, released from irradiated cells, contain carbohydrate-like substances. At maximum far and near UV doses the amounts of these substances constitute 180-190% of the control and 6% of their amount in intact cells. After irradiation with far UV light, relatively high-molecular carbohydrates are released, while near UV light treatment induces the release of low-molecular carbohydrates. The criteria tested show that the efficiency of far UV light exceeds that of near UV light by one order.", "contents": "[Analysis of substances released from Zajdela ascites hepatoma cells exposed to UV radiation of different wavelengths. III. Release of nucleoproteins and carbohydrates]. Irradiation of the Zaidela ascite hepatoma cells with physiological doses of shortwave length (254 nm) and longwave length (300-380 nm) UV light (far and near UV radiation) is accompanied by the release of ribonucleoproteins (RNP) from the cells, whose amounts increase with dose. Irradiation with far and near UV light leads to the release of high-molecular and low-molecular RNP, respectively. No deoxyribonucleoprotein were found among the released substances. Non-protein fractions, released from irradiated cells, contain carbohydrate-like substances. At maximum far and near UV doses the amounts of these substances constitute 180-190% of the control and 6% of their amount in intact cells. After irradiation with far UV light, relatively high-molecular carbohydrates are released, while near UV light treatment induces the release of low-molecular carbohydrates. The criteria tested show that the efficiency of far UV light exceeds that of near UV light by one order."}
{"id": "PMID:199970", "title": "[Effect of light deprivation on enzymic activity of synaptosomes and mitochondria of rabbit cortex visual region].", "content": "The specific activity of markers-enzymes in the subcellular fractions of the rabbit visual analyzer cortical end, the synaptosomes and mitochondria of nerve cells, changed under the effect of early long deprivation. For cytochromoxidase and Na+, K+-ATPase it lowers considerably in all subfractions, for monoaminoxidase and Mg2+-ATPase it rises mainly in synaptosomes; the activity of acetyl cholinesterase lowers per 1 g of tissue. In the light two weeks later a tendency is observed to normalization of the studied indexes. The specific activity of cytochrome oxidase (except for free mitochondria) and Na+, K+-ATPase reaches the control, that of monoaminoxidase also partially normalizes, but not competely; Mg2+ATPase in all the subfractions is more inhibited than in the control. This evidences for the effect of light deprivation on the activity of the enzymes associated with different cycles of metabolic processes, first of all, of oxidation and ion transport. These changes are reversible when visual impulsation is recovered. Disturbances in chemism at the subcellular level are specific for different enzymic systems and are not the same in certain subfractions of great hemispheres.", "contents": "[Effect of light deprivation on enzymic activity of synaptosomes and mitochondria of rabbit cortex visual region]. The specific activity of markers-enzymes in the subcellular fractions of the rabbit visual analyzer cortical end, the synaptosomes and mitochondria of nerve cells, changed under the effect of early long deprivation. For cytochromoxidase and Na+, K+-ATPase it lowers considerably in all subfractions, for monoaminoxidase and Mg2+-ATPase it rises mainly in synaptosomes; the activity of acetyl cholinesterase lowers per 1 g of tissue. In the light two weeks later a tendency is observed to normalization of the studied indexes. The specific activity of cytochrome oxidase (except for free mitochondria) and Na+, K+-ATPase reaches the control, that of monoaminoxidase also partially normalizes, but not competely; Mg2+ATPase in all the subfractions is more inhibited than in the control. This evidences for the effect of light deprivation on the activity of the enzymes associated with different cycles of metabolic processes, first of all, of oxidation and ion transport. These changes are reversible when visual impulsation is recovered. Disturbances in chemism at the subcellular level are specific for different enzymic systems and are not the same in certain subfractions of great hemispheres."}
{"id": "PMID:199971", "title": "[Metabolism and content of proteins in rat tissues under the effect of sodium ribonucleate in experimental hypercorticism].", "content": "Experimental hypercorticism induced by multiple injections of ACTH-zinc-phosphate inhibits the incorporation of 1-14C-alanine and 3H-methionine into proteins of the liver, spleen, musculus quadratus femoris, blood and nuclear plasma, mitochondria, microsomas and cytosol of the liver as well as decreases the protein content in them. Under the effect of ACTH-zinc-phosphate in combination with enteral administration of sodium ribonucleate, the deviations from the normal level in the incorporation of the labelled amino acids into proteins and in the protein content of the tissues under study are less pronounced than under the effect of the hormone only. An opinion is advanced that enteral injection of sodium ribonucleate may be more preferable than parenteral administration of this preparation with hypercorticism under clinical conditions.", "contents": "[Metabolism and content of proteins in rat tissues under the effect of sodium ribonucleate in experimental hypercorticism]. Experimental hypercorticism induced by multiple injections of ACTH-zinc-phosphate inhibits the incorporation of 1-14C-alanine and 3H-methionine into proteins of the liver, spleen, musculus quadratus femoris, blood and nuclear plasma, mitochondria, microsomas and cytosol of the liver as well as decreases the protein content in them. Under the effect of ACTH-zinc-phosphate in combination with enteral administration of sodium ribonucleate, the deviations from the normal level in the incorporation of the labelled amino acids into proteins and in the protein content of the tissues under study are less pronounced than under the effect of the hormone only. An opinion is advanced that enteral injection of sodium ribonucleate may be more preferable than parenteral administration of this preparation with hypercorticism under clinical conditions."}
{"id": "PMID:199972", "title": "[Effect of \"carbostimulin\", vitamin D 3 and their mixture on bone tissue regeneration].", "content": "Healing of the bone injury in rabbits was studied as affected by carbostimulin and its mixture with vitamin D3. Some biochemical indexes: the content of sialic acids, calcium and citric acid in blood serum of the animals, intensity of 14C incorporation from NaH14CO3 into the regenerated bone tissue and its proteins as well as histological studies, data, evidence for a positive effect of the mentioned preparations on the bone substance regeneration in the animals under experiment. So. the content of sialic acids in blood serum normalizes on the 10th day after the operation mostly in the animals which were administered the mixture of the preparations and in which the most pronounced hypercalcemia is observed. Incorporation of 14C from NaH14CO3 into the regenerated tissue and its proteins is most intensive in the same animals.", "contents": "[Effect of \"carbostimulin\", vitamin D 3 and their mixture on bone tissue regeneration]. Healing of the bone injury in rabbits was studied as affected by carbostimulin and its mixture with vitamin D3. Some biochemical indexes: the content of sialic acids, calcium and citric acid in blood serum of the animals, intensity of 14C incorporation from NaH14CO3 into the regenerated bone tissue and its proteins as well as histological studies, data, evidence for a positive effect of the mentioned preparations on the bone substance regeneration in the animals under experiment. So. the content of sialic acids in blood serum normalizes on the 10th day after the operation mostly in the animals which were administered the mixture of the preparations and in which the most pronounced hypercalcemia is observed. Incorporation of 14C from NaH14CO3 into the regenerated tissue and its proteins is most intensive in the same animals."}
{"id": "PMID:199975", "title": "Angiographic features of lateral cervical masses.", "content": "An audible bruit may represent a clue to the vascular nature of the lesion. Angiography is definitely indicated in the presence of pulsatile cervical masses with or without an associated bruit, and should be more widely utilized in the future for evaluation of cervical masses. In addition to the nature of the mass, angiography may also be of value in outlining the extent of the mass and its relationship to major vessels. Magnification and subtraction angiographic techniques with their improved detail may play an important role in clarifying the etiology of cervical masses, and hence facilitate the plan of therapy. If reasonable uncertainty as to the clinical diagnosis exists, angiography should be considered a diagnostic aid.", "contents": "Angiographic features of lateral cervical masses. An audible bruit may represent a clue to the vascular nature of the lesion. Angiography is definitely indicated in the presence of pulsatile cervical masses with or without an associated bruit, and should be more widely utilized in the future for evaluation of cervical masses. In addition to the nature of the mass, angiography may also be of value in outlining the extent of the mass and its relationship to major vessels. Magnification and subtraction angiographic techniques with their improved detail may play an important role in clarifying the etiology of cervical masses, and hence facilitate the plan of therapy. If reasonable uncertainty as to the clinical diagnosis exists, angiography should be considered a diagnostic aid."}
{"id": "PMID:199980", "title": "Melanotic neuro-ectodermal tumour of infancy (melanotic progonoma) in two calves.", "content": "Large unilateral tumours involving the mandible in two calves were composed of melanin-containing cells and small lymphocyte-like cells in a cellular fibrous stroma. These neoplasms resembled the melanotic neuro-ectodermal tumour of infancy.", "contents": "Melanotic neuro-ectodermal tumour of infancy (melanotic progonoma) in two calves. Large unilateral tumours involving the mandible in two calves were composed of melanin-containing cells and small lymphocyte-like cells in a cellular fibrous stroma. These neoplasms resembled the melanotic neuro-ectodermal tumour of infancy."}
{"id": "PMID:199976", "title": "Cranal computed tomography: application to otolaryngology.", "content": "Cranial computed tomography (CT) is an effective radiologic method for the evaluation of extracranial and intracranial pathology. Representative cases of extracranial and intracranial pathology of otolaryngic interest are selected from 6,000 CT scans. Pathology of the nasal cavities, paranasal sinuses, orbits, and cerebellopontine angles is demonstrated.", "contents": "Cranal computed tomography: application to otolaryngology. Cranial computed tomography (CT) is an effective radiologic method for the evaluation of extracranial and intracranial pathology. Representative cases of extracranial and intracranial pathology of otolaryngic interest are selected from 6,000 CT scans. Pathology of the nasal cavities, paranasal sinuses, orbits, and cerebellopontine angles is demonstrated."}
{"id": "PMID:199983", "title": "[Biological properties of the dermopathic bovine herpes (Allerton-mammillitis) virus].", "content": "The dynamics of accumulation and localization of the virus antigen in cells of calf kidney (line CK) was followed by means of immunofluorescence technique. The antigen was detected eight hours (at the very earliest) after infecting the cells. Studied was the immune response of calves vaccinated with an inactivated virus and the addition of an adjuvant. Two weeks following revaccination high titres of virus-neutralizing and complement-fixing antibodies were established in the blood serum of the calves. These results made it reasonable to believe that the inactivated virus is suitable as a vaccinal antigen.", "contents": "[Biological properties of the dermopathic bovine herpes (Allerton-mammillitis) virus]. The dynamics of accumulation and localization of the virus antigen in cells of calf kidney (line CK) was followed by means of immunofluorescence technique. The antigen was detected eight hours (at the very earliest) after infecting the cells. Studied was the immune response of calves vaccinated with an inactivated virus and the addition of an adjuvant. Two weeks following revaccination high titres of virus-neutralizing and complement-fixing antibodies were established in the blood serum of the calves. These results made it reasonable to believe that the inactivated virus is suitable as a vaccinal antigen."}
{"id": "PMID:199984", "title": "[Morphological changes in the kidneys of pigs with an adenovirus infection].", "content": "Dystrophic and necrobiotic changes developed in the epithelium of the kidney tubuli of sucking pigs spontaneously and experimentally infected with adenoviruses. The epithelial cells showed hyperchromatosis of the nuclei, breaking up of the chromatin, and formation of nuclear function bodies. The swelling of the dystrophic cells produced certain amount of pressure on the adjacent capillaries. The pale colour of the kidney itselt was due to the dystrophy of the epithelium and the compression anemia. After the desquamation of the degenerated epithelial cells and their carrying away with the urine the capillaries became strongly dilatated. Groups of adjacent capillaries became macroscopically visible and assumed the appearance of a petechia. Edema in lymphoidcell proliferation were established in the interstitial tissue.", "contents": "[Morphological changes in the kidneys of pigs with an adenovirus infection]. Dystrophic and necrobiotic changes developed in the epithelium of the kidney tubuli of sucking pigs spontaneously and experimentally infected with adenoviruses. The epithelial cells showed hyperchromatosis of the nuclei, breaking up of the chromatin, and formation of nuclear function bodies. The swelling of the dystrophic cells produced certain amount of pressure on the adjacent capillaries. The pale colour of the kidney itselt was due to the dystrophy of the epithelium and the compression anemia. After the desquamation of the degenerated epithelial cells and their carrying away with the urine the capillaries became strongly dilatated. Groups of adjacent capillaries became macroscopically visible and assumed the appearance of a petechia. Edema in lymphoidcell proliferation were established in the interstitial tissue."}
{"id": "PMID:199985", "title": "[Studies of the CFT in the diagnosis of Aujeszky's disease virus in swine].", "content": "It was found that the complement-fixation test is a prompt and suitable method in the diagnosis of the Aujeszky's disease virus, the antigen employed being a cell culture virus. A virulent virus, a slightly virulent one, and the vaccinal mutant strain MK have shown a good complement-fixing activity and they detect specific complement-fixing antibodies in the immune serum. By means of cross CFT an antigenic relation has been established between some strains of the Herpes group and the Aujeszky's disease virus, it being predominantly unilatera. In Aujeszky's disease antisera neutralizing and complement fixing antibodies have been deomonstrated in titres up to 1:64, and in MK antisera--CF-antibodies only. In blood sera from farms with a moderate course in the manifestation of Aujeszky's disease the titre of the CF-antibodies has been 1:8.", "contents": "[Studies of the CFT in the diagnosis of Aujeszky's disease virus in swine]. It was found that the complement-fixation test is a prompt and suitable method in the diagnosis of the Aujeszky's disease virus, the antigen employed being a cell culture virus. A virulent virus, a slightly virulent one, and the vaccinal mutant strain MK have shown a good complement-fixing activity and they detect specific complement-fixing antibodies in the immune serum. By means of cross CFT an antigenic relation has been established between some strains of the Herpes group and the Aujeszky's disease virus, it being predominantly unilatera. In Aujeszky's disease antisera neutralizing and complement fixing antibodies have been deomonstrated in titres up to 1:64, and in MK antisera--CF-antibodies only. In blood sera from farms with a moderate course in the manifestation of Aujeszky's disease the titre of the CF-antibodies has been 1:8."}
{"id": "PMID:199986", "title": "[Attempts at specific immunoprophylaxis against herpes mammillitis].", "content": "A live cell culture adsorbate vaccine was produced against herpes mammillitis in cattle. Comparative investigations were carried out on the immunogenic properties of four vaccines having different adjuvants--aluminum hydroxide, saponin, arlacell, and Freund's adjuvant. All tested vaccines proved harmless and immunogenic for sensitive cattle, the highest immunogenic effect being produced by the vaccine that contained aluminum hydroxide and Freund's adjuvant. The vaccinated animals reacted to immunization with the formation of specific antibodies that showed a highest titre between the 21st and 28th day following treatment. Immunity was checked through challenge on the 45th day, all immunized heifers being fully protected against Bovid herpesvirus infection 2 infection. When necessary the vaccine can be used successfully in a dose of 3-6 cm3, subcutaneously, in the region of the dewlap.", "contents": "[Attempts at specific immunoprophylaxis against herpes mammillitis]. A live cell culture adsorbate vaccine was produced against herpes mammillitis in cattle. Comparative investigations were carried out on the immunogenic properties of four vaccines having different adjuvants--aluminum hydroxide, saponin, arlacell, and Freund's adjuvant. All tested vaccines proved harmless and immunogenic for sensitive cattle, the highest immunogenic effect being produced by the vaccine that contained aluminum hydroxide and Freund's adjuvant. The vaccinated animals reacted to immunization with the formation of specific antibodies that showed a highest titre between the 21st and 28th day following treatment. Immunity was checked through challenge on the 45th day, all immunized heifers being fully protected against Bovid herpesvirus infection 2 infection. When necessary the vaccine can be used successfully in a dose of 3-6 cm3, subcutaneously, in the region of the dewlap."}
{"id": "PMID:199987", "title": "[Pathogenesis of Aujeszky's disease].", "content": "Results are presented of studies on the various localization of the virus of Aujeszky's disease (the avirulent mutant strain MK and the virulent strain 2) in the organism of experimentally infected pigs. At the oral infection of pigs with strain MK the virus has been isolated from the submandibular lymph nodes of the animals only, the pigs being killed on the second and fifth day following infection with a low plaque-forming titer. However, from pigs that have been infected subcutaneously no virus was isolated. In experiments with the virulent strain 2, 15 out of 20 pigs have died up to the seventh day following infection. The examination has revealed that a virus of a high plaque-forming titer was present in almost all organs. Histologic investigations in the experiments with the virulent strain 2 have revealed the presence of a strongly manifested nonsuppurative encephalitis, interstitial pneumonia, necroses, and nuclear inclusion bodies. In the experiments with strain MK these changes have been much more slightly expressed, and after the tenth day of infection they tended to disappear. In the authors' opinion the changes are due to the 'interaction' between the viral particles of the vaccinal virus and the competent cells, being the cytologic manifestation of the enhanced immunobiologic status of the host organism. This is an expression of the cell manifestation of immunogenesis and not of the toxic injury of cells which has been observed in experiments with the virulent strain.", "contents": "[Pathogenesis of Aujeszky's disease]. Results are presented of studies on the various localization of the virus of Aujeszky's disease (the avirulent mutant strain MK and the virulent strain 2) in the organism of experimentally infected pigs. At the oral infection of pigs with strain MK the virus has been isolated from the submandibular lymph nodes of the animals only, the pigs being killed on the second and fifth day following infection with a low plaque-forming titer. However, from pigs that have been infected subcutaneously no virus was isolated. In experiments with the virulent strain 2, 15 out of 20 pigs have died up to the seventh day following infection. The examination has revealed that a virus of a high plaque-forming titer was present in almost all organs. Histologic investigations in the experiments with the virulent strain 2 have revealed the presence of a strongly manifested nonsuppurative encephalitis, interstitial pneumonia, necroses, and nuclear inclusion bodies. In the experiments with strain MK these changes have been much more slightly expressed, and after the tenth day of infection they tended to disappear. In the authors' opinion the changes are due to the 'interaction' between the viral particles of the vaccinal virus and the competent cells, being the cytologic manifestation of the enhanced immunobiologic status of the host organism. This is an expression of the cell manifestation of immunogenesis and not of the toxic injury of cells which has been observed in experiments with the virulent strain."}
{"id": "PMID:199988", "title": "[Relationship between the chemical structure and the biological activity of antibodies against the foot-and-mouth disease virus].", "content": "Investigated was the effect of various amino agents (stained and phthalic anhydride and sulfopicric acid) on the complement-and antigen-fixing activity of IgG and IgM antibodies isolated from guinea pig sera, the donor animals being hyperimmunzed with type O, strain Polyana, of the foot-and-mouth disease virus, At the moderate modification (75-86 per cent acetylation, and 36-40 per cent 'phthalation') of the primary amino groups the foot-and-mouth disease antibodies retained only half of the conjugation caused greater and complete loss of this activity. IgG and IgM showed almost equal specificity with regard to the antigen that had induced them. The lowered complement-fixing capacity was shown to have no specific effect on the primary relation of the foot-and-mouth disease virus to the antibody. Chemical modifying agents inactivated the specific small, strongly defined complement-fixing zones in the Fc-fragment of the foot-and-mouth disease antibody molecule.", "contents": "[Relationship between the chemical structure and the biological activity of antibodies against the foot-and-mouth disease virus]. Investigated was the effect of various amino agents (stained and phthalic anhydride and sulfopicric acid) on the complement-and antigen-fixing activity of IgG and IgM antibodies isolated from guinea pig sera, the donor animals being hyperimmunzed with type O, strain Polyana, of the foot-and-mouth disease virus, At the moderate modification (75-86 per cent acetylation, and 36-40 per cent 'phthalation') of the primary amino groups the foot-and-mouth disease antibodies retained only half of the conjugation caused greater and complete loss of this activity. IgG and IgM showed almost equal specificity with regard to the antigen that had induced them. The lowered complement-fixing capacity was shown to have no specific effect on the primary relation of the foot-and-mouth disease virus to the antibody. Chemical modifying agents inactivated the specific small, strongly defined complement-fixing zones in the Fc-fragment of the foot-and-mouth disease antibody molecule."}
{"id": "PMID:199989", "title": "Histologic variants of lipid-secreting carcinoma of the breast.", "content": "Ten new cases of so-called lipid-secreting carcinomas of the breast are presented. Histopathologic analysis suggests three different microscopical patterns which are all characterized by abundant intracytoplasmic neutral fat deposits. Review of the literature yielded only 15 well-documented cases. Diagnostic problems are emphasized, with special regard to the secretory differentiation of normal and neoplastic mammary cells.", "contents": "Histologic variants of lipid-secreting carcinoma of the breast. Ten new cases of so-called lipid-secreting carcinomas of the breast are presented. Histopathologic analysis suggests three different microscopical patterns which are all characterized by abundant intracytoplasmic neutral fat deposits. Review of the literature yielded only 15 well-documented cases. Diagnostic problems are emphasized, with special regard to the secretory differentiation of normal and neoplastic mammary cells."}
{"id": "PMID:199999", "title": "[Changes in organelle-specific enzyme activity and the ultrastructure of liver cells in cholelithiasis].", "content": "Activities of organelle specific enzymes (succinate dehydrogenase, glucose-6-phosphatase, acidic DNAase, acidic RNAase, acidic and alkaline phosphatases) were measured in homogenates and subcellular fractions of liver tissue of patients with cholelithic disease. Liver tissue samples analyzed were investigated also by light and electron microscopy. The data obtained were considered in connection with localization of cholelith in biliary system, type of inflammation, presence of subhepatic cholestasis and of accompanying syndrome of pancreatitis. Typical alterations were observed in the activity of organelle specific enzymes and in the ultrastructure of mitochindria, lysosomes and endoplasmic reticulum in cholelithic disease. The most distinct alterations in the enzymatic activities were found in choledocholithiasis as well as in subhepatic jaundice.", "contents": "[Changes in organelle-specific enzyme activity and the ultrastructure of liver cells in cholelithiasis]. Activities of organelle specific enzymes (succinate dehydrogenase, glucose-6-phosphatase, acidic DNAase, acidic RNAase, acidic and alkaline phosphatases) were measured in homogenates and subcellular fractions of liver tissue of patients with cholelithic disease. Liver tissue samples analyzed were investigated also by light and electron microscopy. The data obtained were considered in connection with localization of cholelith in biliary system, type of inflammation, presence of subhepatic cholestasis and of accompanying syndrome of pancreatitis. Typical alterations were observed in the activity of organelle specific enzymes and in the ultrastructure of mitochindria, lysosomes and endoplasmic reticulum in cholelithic disease. The most distinct alterations in the enzymatic activities were found in choledocholithiasis as well as in subhepatic jaundice."}
{"id": "PMID:200001", "title": "[Interrelationships between lipids and scleroproteins in silicosis caused by crystalline and condensed modifications of silicon].", "content": "Accumulation of lipids, including phospholipids, in lungs was accompanied by a proliferative-cellular reaction. The proliferation of cells was caused by accumulation of lipids. One of possible mechanisms of interrelation between lipids and collagen synthesis was as follows: in silicosis degradation of macrophages was accompanied by secretion into the medium of phospholipids, which inhibited free radical oxidation; in this case the decreased formation of cytotoxic products caused the cell proliferation, including fibroblasts, which produced collagen. The importance of lipids in collagen formation was corroborated: by accumulation of lipids, which preceded the hydroxyproline increase (scleroproteins, collagen), by development of the proliferative-cellular reaction together with the higher phospholipid-hydroxyproline level as compared with control, by formation of earlier sclerosis of silicotic nodes in \"condensed\" silicosis with the simultaneous increase in absolute content of phospholipids and total lipids. This role of lipids was also supported by the observed correlation between the absolute contents of scleroproteins and lipids within all steps of \"quartz\" silicosis development.", "contents": "[Interrelationships between lipids and scleroproteins in silicosis caused by crystalline and condensed modifications of silicon]. Accumulation of lipids, including phospholipids, in lungs was accompanied by a proliferative-cellular reaction. The proliferation of cells was caused by accumulation of lipids. One of possible mechanisms of interrelation between lipids and collagen synthesis was as follows: in silicosis degradation of macrophages was accompanied by secretion into the medium of phospholipids, which inhibited free radical oxidation; in this case the decreased formation of cytotoxic products caused the cell proliferation, including fibroblasts, which produced collagen. The importance of lipids in collagen formation was corroborated: by accumulation of lipids, which preceded the hydroxyproline increase (scleroproteins, collagen), by development of the proliferative-cellular reaction together with the higher phospholipid-hydroxyproline level as compared with control, by formation of earlier sclerosis of silicotic nodes in \"condensed\" silicosis with the simultaneous increase in absolute content of phospholipids and total lipids. This role of lipids was also supported by the observed correlation between the absolute contents of scleroproteins and lipids within all steps of \"quartz\" silicosis development."}
{"id": "PMID:200000", "title": "[Lipid metabolism of neonatally thymectomized rats of different sexes].", "content": "Content of cholesterol, its esters, total beta-lipoproteins and free fatty acids was increased in blood serum of rats, subjected to thymectomia after birth. The distinct sex variations were found in alterations of these patterns. Content of cholesterol was increased only in thymectomized males at the age of 3 months; content of beta-lipoproteins in males was elevated earlier and to higher level as compared wtih females. Alteration in content of blood serum lipids did not depend on manifestations of exhaustion syndrome (typical consequence of neonatal thymectomia) but it was related to ablation of thymus; this suggests that thymus participates in regulation of lipid metabolism. Sex differences in alterations of lipid metabolism patterns enabled to assume the existence of endocrine interrelations between thymus and sex glands.", "contents": "[Lipid metabolism of neonatally thymectomized rats of different sexes]. Content of cholesterol, its esters, total beta-lipoproteins and free fatty acids was increased in blood serum of rats, subjected to thymectomia after birth. The distinct sex variations were found in alterations of these patterns. Content of cholesterol was increased only in thymectomized males at the age of 3 months; content of beta-lipoproteins in males was elevated earlier and to higher level as compared wtih females. Alteration in content of blood serum lipids did not depend on manifestations of exhaustion syndrome (typical consequence of neonatal thymectomia) but it was related to ablation of thymus; this suggests that thymus participates in regulation of lipid metabolism. Sex differences in alterations of lipid metabolism patterns enabled to assume the existence of endocrine interrelations between thymus and sex glands."}
{"id": "PMID:200002", "title": "[Age and changes in the activity of several energy metabolism enzymes in the rabbit aorta].", "content": "Age alterations in the activity of several key enzymes of glucose oxidative breakdown (hexokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and cytochrome c oxidase) were studied in extracts from rabbit aorta. The hexokinase activity was measured also in mitochondrial fraction. The activity of all the enzymes studied in rabbit aorta (calculated either per 1 g of the tissue or per 1 mg of proteins) was the highest at the age from 1-2 weeks to 1 month. The minimal activity was observed in adult animals, which were 1-2 years old, In aorta of 3,5-4 years old rabbits an increase (per 1 g of the tissue) in the activity of the enzymes was observed.", "contents": "[Age and changes in the activity of several energy metabolism enzymes in the rabbit aorta]. Age alterations in the activity of several key enzymes of glucose oxidative breakdown (hexokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and cytochrome c oxidase) were studied in extracts from rabbit aorta. The hexokinase activity was measured also in mitochondrial fraction. The activity of all the enzymes studied in rabbit aorta (calculated either per 1 g of the tissue or per 1 mg of proteins) was the highest at the age from 1-2 weeks to 1 month. The minimal activity was observed in adult animals, which were 1-2 years old, In aorta of 3,5-4 years old rabbits an increase (per 1 g of the tissue) in the activity of the enzymes was observed."}
{"id": "PMID:200003", "title": "[Activity of enzymes of glycolysis and gluconeogenesis in primary hepatomas induced by diethylnitrosamine].", "content": "Activities of the key enzymes of glycolysis and gluconeogenesis were studied in soluble fraction of primary hepatoma, induced by diethyl nitrosamine (DENA) in rats and mice of C3HA strain. Histological structure of the tumors studied showed that they belonged mainly to highly differentiated hepatocellular adenomas. Liver tissue of the animals which were not treated with DENA, was used as a control. The hexokinase activity was increased about 2-fold in the rat hepatomas and 3-fold--in the mice hepatomas. In primary hepatomas the glucokinase activity was unaltered or slightly decreased; the fructokinase activity was distinctly decreased (in several cases down to zero). The activity of key enzymes of gluconeogenesis--glucose-6-phosphatase and fructose-1,6-diphosphatase--was distinctly decreased, especially the activity of the former enzyme, which constituted in hepatomas about 1/6 of the activity found in liver tissue.", "contents": "[Activity of enzymes of glycolysis and gluconeogenesis in primary hepatomas induced by diethylnitrosamine]. Activities of the key enzymes of glycolysis and gluconeogenesis were studied in soluble fraction of primary hepatoma, induced by diethyl nitrosamine (DENA) in rats and mice of C3HA strain. Histological structure of the tumors studied showed that they belonged mainly to highly differentiated hepatocellular adenomas. Liver tissue of the animals which were not treated with DENA, was used as a control. The hexokinase activity was increased about 2-fold in the rat hepatomas and 3-fold--in the mice hepatomas. In primary hepatomas the glucokinase activity was unaltered or slightly decreased; the fructokinase activity was distinctly decreased (in several cases down to zero). The activity of key enzymes of gluconeogenesis--glucose-6-phosphatase and fructose-1,6-diphosphatase--was distinctly decreased, especially the activity of the former enzyme, which constituted in hepatomas about 1/6 of the activity found in liver tissue."}
{"id": "PMID:200007", "title": "[Effect of radiation on the activity of lactate dehydrogenase and acid phosphatase isoenzymes of Zajdela hepatoma].", "content": "In cells of ascites Zajdela hepatoma in different terms after irradiation of the abdominal region in tumor-bearing rats (doses of 500, 700 and 1000 rad) there were found a reduction of highly active and an increase of insignificantly active normal isoenzymes of lactate dehydrogenase and also disorders in the content of acid phosphatase.", "contents": "[Effect of radiation on the activity of lactate dehydrogenase and acid phosphatase isoenzymes of Zajdela hepatoma]. In cells of ascites Zajdela hepatoma in different terms after irradiation of the abdominal region in tumor-bearing rats (doses of 500, 700 and 1000 rad) there were found a reduction of highly active and an increase of insignificantly active normal isoenzymes of lactate dehydrogenase and also disorders in the content of acid phosphatase."}
{"id": "PMID:200008", "title": "[Advantages of the Eagle medium over saline solutions in the studies of the metabolic parameters of tumor cells in vitro].", "content": "In two media (krebsringer phosphate and phosphate-enriched Eagle medium) the indices of energetic metabolism (respiration, glycolysis. ATP content) were determined and the metabolism of macromolecular compounds (c-RNA) of Ehrlich carcinoma ascitic cells was investigated. The results of studies of ascites tumor cells metabolism have indicated considerable advantages of phosphate-enriched Eagle medium over krebs ringer phosphate buffer.", "contents": "[Advantages of the Eagle medium over saline solutions in the studies of the metabolic parameters of tumor cells in vitro]. In two media (krebsringer phosphate and phosphate-enriched Eagle medium) the indices of energetic metabolism (respiration, glycolysis. ATP content) were determined and the metabolism of macromolecular compounds (c-RNA) of Ehrlich carcinoma ascitic cells was investigated. The results of studies of ascites tumor cells metabolism have indicated considerable advantages of phosphate-enriched Eagle medium over krebs ringer phosphate buffer."}
{"id": "PMID:200005", "title": "[Effect of pepsin on low density serum lipoproteins].", "content": "Native lipoproteins of low density from human blood serum were intensively hydrolyzed by pepsin in 0.1 M solution of beta-alanine-HCl at pH 1.9. About 50% and 90% of all the protein part of the substances were split off within 60 min and 22 hrs, respectively. Analytical ultracentrifugation showed that the proteolysis occurred in several steps with formation of discrete intermediates (sedimentation coefficients 2.9 S and 2.3 S at solution density 1,012 g/ml).", "contents": "[Effect of pepsin on low density serum lipoproteins]. Native lipoproteins of low density from human blood serum were intensively hydrolyzed by pepsin in 0.1 M solution of beta-alanine-HCl at pH 1.9. About 50% and 90% of all the protein part of the substances were split off within 60 min and 22 hrs, respectively. Analytical ultracentrifugation showed that the proteolysis occurred in several steps with formation of discrete intermediates (sedimentation coefficients 2.9 S and 2.3 S at solution density 1,012 g/ml)."}
{"id": "PMID:200011", "title": "[Interfering and interferonogenic activity of attenuated and original para-influenza viral strains].", "content": "A higher interfering activity of attenuated (vaccine) strains of parainfluenza virus types 1, 2 and 3 which had undergone a long-term adaptation to cell cultures as compared to the original viruses was established. The interferon-inducing activity of vaccine parainfluenza virus types 2 and 3 was also higher than that of the original viruses. The high interfering and interferon-inducing activity of attenuated parainfluenza virus strains of type 2 and 3 correlated with reduced virulence of these variants for man. These tests may be used for the assessment of virulence of parainfluenza virus strains type 2 and 3 in the laboratory.", "contents": "[Interfering and interferonogenic activity of attenuated and original para-influenza viral strains]. A higher interfering activity of attenuated (vaccine) strains of parainfluenza virus types 1, 2 and 3 which had undergone a long-term adaptation to cell cultures as compared to the original viruses was established. The interferon-inducing activity of vaccine parainfluenza virus types 2 and 3 was also higher than that of the original viruses. The high interfering and interferon-inducing activity of attenuated parainfluenza virus strains of type 2 and 3 correlated with reduced virulence of these variants for man. These tests may be used for the assessment of virulence of parainfluenza virus strains type 2 and 3 in the laboratory."}
{"id": "PMID:200013", "title": "[Characteristics of the biological properties of a Kemerovo group arbovirus isolated in Transcarpathia].", "content": "A strain of an arbovirus named Mircha was isolated from Ixodes ricinus L. ticks (30 incompletely engorged females) collected in May, 1972 from cows pastured in a forest near the village of Mircha of the Velikobereznyansky district of the Zakarpathye region of the Ukrainian SSR. The strain was found to be pathogenic for newborn white mice and rats by the intracerebral and intraperitoneal routes and for chick embryos inoculated into the yolk sac, to replicate in chick embryo fibroblast culture producing a marked cytopathic effect to be relatively stable to ethyl ether and sodium deoxylate. On the basis of the results of serological identification (CFT) it was classified into arboviruses of the Kemerovo group, the antigenic subgroup Kemeroxo-Tribec. The factors of natural focality are described briefly, and the results of the study of virus persistence in adult white mice, rats, and guinea pigs and of its immunodepressive effect are presented.", "contents": "[Characteristics of the biological properties of a Kemerovo group arbovirus isolated in Transcarpathia]. A strain of an arbovirus named Mircha was isolated from Ixodes ricinus L. ticks (30 incompletely engorged females) collected in May, 1972 from cows pastured in a forest near the village of Mircha of the Velikobereznyansky district of the Zakarpathye region of the Ukrainian SSR. The strain was found to be pathogenic for newborn white mice and rats by the intracerebral and intraperitoneal routes and for chick embryos inoculated into the yolk sac, to replicate in chick embryo fibroblast culture producing a marked cytopathic effect to be relatively stable to ethyl ether and sodium deoxylate. On the basis of the results of serological identification (CFT) it was classified into arboviruses of the Kemerovo group, the antigenic subgroup Kemeroxo-Tribec. The factors of natural focality are described briefly, and the results of the study of virus persistence in adult white mice, rats, and guinea pigs and of its immunodepressive effect are presented."}
{"id": "PMID:200010", "title": "[Isolation and characteristics of messenger RNA for antiviral protein].", "content": "Experimental data on the induction and isolation of functionally active mRNA's for antiviral protein (AVP) from interferon-treated cells are presented. The dynamics of mRNA-AVP translation in homologous cells and sedimentational distribution of the total and poly(A)-containing preparation of mRNA-AVP in sucrose density gradients were studied.", "contents": "[Isolation and characteristics of messenger RNA for antiviral protein]. Experimental data on the induction and isolation of functionally active mRNA's for antiviral protein (AVP) from interferon-treated cells are presented. The dynamics of mRNA-AVP translation in homologous cells and sedimentational distribution of the total and poly(A)-containing preparation of mRNA-AVP in sucrose density gradients were studied."}
{"id": "PMID:200012", "title": "[Abortive myxovirus infection in Ehrlich's ascitic carcinoma cells. Further study of the nature of the virus-specific structures produced by heterokaryons].", "content": "Fowl plague virus-infected cells of Ehrlich ascitic carcinoma produce a noninfectious virus which is defective in fragility of its membranes. An attempt has been made to produce nondefective virus by fusion of infected Ehrlich cells with permissive cells: infected and non-infected chicken fibroblasts. The fusion of FPV-infected and 3H-uridine labeled Ehrlich ascitic carcinoma cells with infected unlabeled chicken fibroblasts using inactivated Sendai virus resulted in production of two types of labeled virus particles: with a buoyant density in cesium chloride gradient of 1.29 g/cm3 characteristic of particles produced by infected Ehrlich cells and buoyant density 1.22 g/cm3 typical of standard influenza virus. Both types of particles has infectious activity which was greater in the virus with the density of 1.22 g/cm3. However, particles with the density of 1.22 g/cm3 are not found upon the fusion of infected Ehrlich cells with uninfected chicken fibroblasts, with chicken fibroblasts early after infection, or with chicken fibroblasts treated with actinomycin D before infection. Infected chicken fibroblasts in hybrids were shown not to use the radioactive pool of Ehrlich cells and, accordingly, the virus with the density of 1.22 g/cm3 if formed from components pre-existing in Ehrlich cells. It is suggested that the standard virus buds on the areas of membranes of permissive cells which are parts of the hybrids.", "contents": "[Abortive myxovirus infection in Ehrlich's ascitic carcinoma cells. Further study of the nature of the virus-specific structures produced by heterokaryons]. Fowl plague virus-infected cells of Ehrlich ascitic carcinoma produce a noninfectious virus which is defective in fragility of its membranes. An attempt has been made to produce nondefective virus by fusion of infected Ehrlich cells with permissive cells: infected and non-infected chicken fibroblasts. The fusion of FPV-infected and 3H-uridine labeled Ehrlich ascitic carcinoma cells with infected unlabeled chicken fibroblasts using inactivated Sendai virus resulted in production of two types of labeled virus particles: with a buoyant density in cesium chloride gradient of 1.29 g/cm3 characteristic of particles produced by infected Ehrlich cells and buoyant density 1.22 g/cm3 typical of standard influenza virus. Both types of particles has infectious activity which was greater in the virus with the density of 1.22 g/cm3. However, particles with the density of 1.22 g/cm3 are not found upon the fusion of infected Ehrlich cells with uninfected chicken fibroblasts, with chicken fibroblasts early after infection, or with chicken fibroblasts treated with actinomycin D before infection. Infected chicken fibroblasts in hybrids were shown not to use the radioactive pool of Ehrlich cells and, accordingly, the virus with the density of 1.22 g/cm3 if formed from components pre-existing in Ehrlich cells. It is suggested that the standard virus buds on the areas of membranes of permissive cells which are parts of the hybrids."}
{"id": "PMID:200018", "title": "[Biochemical methods in the assessment of activity in rheumatoid arthritis (author's transl)].", "content": "An investigation was carried out in 120 patients with classical rheumatoid arthritis (RA). Prolylhydroxylase activity was determined in the synovial membrane and serum and compared with the level of collagen-like protein in plasma and the hydroxyproline-creatinine quotient in urine. The data were related to the activity of RA as measured according to Voit and Gamp and also according to Lansbury. Activity was, furthermore, also assessed on the basis of newly defined criteria considering clinical, biochemical and histological findings. Prolylhydroxylase activity was significantly correlated to the activity of the RA assessed according to each of these systems. The significance of the known parameters, collagen-like protein in plasma and hydroxyproline-creatinine quotient in urine were confirmed in this larger series of patients. The positive correlation between prolylhydroxylase activities in the synovial membrane, as well as in serum, and the level of collagen metabolites in plasma and urine corroborated the value of biochemical methods in the assessment of activity of RA in order to undertake differentiated therapy.", "contents": "[Biochemical methods in the assessment of activity in rheumatoid arthritis (author's transl)]. An investigation was carried out in 120 patients with classical rheumatoid arthritis (RA). Prolylhydroxylase activity was determined in the synovial membrane and serum and compared with the level of collagen-like protein in plasma and the hydroxyproline-creatinine quotient in urine. The data were related to the activity of RA as measured according to Voit and Gamp and also according to Lansbury. Activity was, furthermore, also assessed on the basis of newly defined criteria considering clinical, biochemical and histological findings. Prolylhydroxylase activity was significantly correlated to the activity of the RA assessed according to each of these systems. The significance of the known parameters, collagen-like protein in plasma and hydroxyproline-creatinine quotient in urine were confirmed in this larger series of patients. The positive correlation between prolylhydroxylase activities in the synovial membrane, as well as in serum, and the level of collagen metabolites in plasma and urine corroborated the value of biochemical methods in the assessment of activity of RA in order to undertake differentiated therapy."}
{"id": "PMID:200015", "title": "[Use of immune electron microscopy for detecting the hepatitis A virus].", "content": "Attempts were made to isolate and identify hepatitis A virus by the method of immune electron microscopy using also biophysical methods and the transfection procedure of cell cultures by nucleic acid preparations. In fecal specimens from patients with infectious hepatitis A, virus-like particles 25-30 nm in diameter were found which reacted with convalescent antisera and could be detected by the immune electron microscopy method. By the same method virus-like particles 22-25 nm in diameter were detected in the blood serum of the patients collected early in the disease. A method for their purification and concentration in cesium chloride density gradients has been developed. Attempts at transfection of the cell cultures with preparations of nucleic acids failed. In the course of the study, however, data were obtained which would subsequently facilitate isolation of the causative agent of hepatitis A.", "contents": "[Use of immune electron microscopy for detecting the hepatitis A virus]. Attempts were made to isolate and identify hepatitis A virus by the method of immune electron microscopy using also biophysical methods and the transfection procedure of cell cultures by nucleic acid preparations. In fecal specimens from patients with infectious hepatitis A, virus-like particles 25-30 nm in diameter were found which reacted with convalescent antisera and could be detected by the immune electron microscopy method. By the same method virus-like particles 22-25 nm in diameter were detected in the blood serum of the patients collected early in the disease. A method for their purification and concentration in cesium chloride density gradients has been developed. Attempts at transfection of the cell cultures with preparations of nucleic acids failed. In the course of the study, however, data were obtained which would subsequently facilitate isolation of the causative agent of hepatitis A."}
{"id": "PMID:200019", "title": "[Pz peptidase activity in serum (author's transl)].", "content": "Synthetic PZ peptide, synthesized by W\u00fcnsch and Heidrich, was used as substrate to determine PZ peptidase activities in the sera of man, rabbit, guinea pig and mouse. The PZ peptidase from rabbit serum was purified 200 fold and characterized. The enzyme has an isoelectric point of 5.0 and pH optima at pH 7.2 and pH 7.9. Its behaviour on gel filtration points to a molecular weight of 60.000 dalton. The peptidase is inhibited by heavy metal ions, SH reagents and serum. Ca ions are EDTA are without any effect. In contrast to collagen peptidases from micro-organisms, the enzyme from rabbit serum does not attack native, but only denatured collagen. The results suggest that PZ peptidases participate in collagen breakdown by cleaving the collagen fragments which are released by the collagenases.", "contents": "[Pz peptidase activity in serum (author's transl)]. Synthetic PZ peptide, synthesized by W\u00fcnsch and Heidrich, was used as substrate to determine PZ peptidase activities in the sera of man, rabbit, guinea pig and mouse. The PZ peptidase from rabbit serum was purified 200 fold and characterized. The enzyme has an isoelectric point of 5.0 and pH optima at pH 7.2 and pH 7.9. Its behaviour on gel filtration points to a molecular weight of 60.000 dalton. The peptidase is inhibited by heavy metal ions, SH reagents and serum. Ca ions are EDTA are without any effect. In contrast to collagen peptidases from micro-organisms, the enzyme from rabbit serum does not attack native, but only denatured collagen. The results suggest that PZ peptidases participate in collagen breakdown by cleaving the collagen fragments which are released by the collagenases."}
{"id": "PMID:200014", "title": "[Study of the synthesis of Rous virus-specific RNA in chick embryo cells].", "content": "The presence of virus-specific RNA in commercial chick embryos and its lack in chick embryos of leukemia-free chicken farm of the USSR AMS Oncological Research Center as well as in cell cultures from RIF-free chicken infected with Marek's disease virus was demonstrated by hybridizationof 3H-DNA-product of Rous sarcoma virus synthesized in vitro in the presence of actinomycin D with the total preparation of cellular RNA.", "contents": "[Study of the synthesis of Rous virus-specific RNA in chick embryo cells]. The presence of virus-specific RNA in commercial chick embryos and its lack in chick embryos of leukemia-free chicken farm of the USSR AMS Oncological Research Center as well as in cell cultures from RIF-free chicken infected with Marek's disease virus was demonstrated by hybridizationof 3H-DNA-product of Rous sarcoma virus synthesized in vitro in the presence of actinomycin D with the total preparation of cellular RNA."}
{"id": "PMID:200016", "title": "[Study of the vaccinating properties of 2 variants of Marek's disease virus].", "content": "The vaccinating properties of two variants of Marek's disease virus, Kekava strain (MDV-Kekava) have been studied. One of them is naturally attenuated, the other has been produced as a result of attenuation of the pathogenic MDV-Kekava by long-term passages in chick embryo fibroblast (CEF) culture. The vaccinating properties of the naturally attenuated strains (MDV-Kekava 83) were first studied in an experiment in which the blood of chicken No. 1683 was used as the vaccine. In paralled. the MDV-Kekava 83 variant was isolated from the blood of this chicken in CEF culture. Vaccination of chickens with the blood of this chicken as well as with 1000-3000 PFU MDV-Kekava 83 which had undergone 16, 24, 45, and 46 passages in vitro produced in the chickens resistance to Marek's disease. According to the combined data of 4 experiments, altogether 9 out of 101 vaccinated chickens developed Marek's disease. Among the controls inoculated with the pathogenic MDV alone 51 out of 137 chickens developed the disease. Attenuation of the pathogenic MDV-Kekava 55 in CEF culture occurred very slowly. The virus of the 45th passage in vitro had no vaccinating properties. Vaccination of the chickens with 1000-2500 PFU MDV-Kekava 56 which had undergone  73 a94 passages in CEF culture produced resistance to Marek's disease. Among the vaccinated chickens 20 out of 113 had Marek's disease whereas in the control group 74 out of 122 were observed to develop the disease. Among the chickens vaccinated with MDV, 3-4% developed the disease. Possible causes of the disease in this group of chickens are discussed.", "contents": "[Study of the vaccinating properties of 2 variants of Marek's disease virus]. The vaccinating properties of two variants of Marek's disease virus, Kekava strain (MDV-Kekava) have been studied. One of them is naturally attenuated, the other has been produced as a result of attenuation of the pathogenic MDV-Kekava by long-term passages in chick embryo fibroblast (CEF) culture. The vaccinating properties of the naturally attenuated strains (MDV-Kekava 83) were first studied in an experiment in which the blood of chicken No. 1683 was used as the vaccine. In paralled. the MDV-Kekava 83 variant was isolated from the blood of this chicken in CEF culture. Vaccination of chickens with the blood of this chicken as well as with 1000-3000 PFU MDV-Kekava 83 which had undergone 16, 24, 45, and 46 passages in vitro produced in the chickens resistance to Marek's disease. According to the combined data of 4 experiments, altogether 9 out of 101 vaccinated chickens developed Marek's disease. Among the controls inoculated with the pathogenic MDV alone 51 out of 137 chickens developed the disease. Attenuation of the pathogenic MDV-Kekava 55 in CEF culture occurred very slowly. The virus of the 45th passage in vitro had no vaccinating properties. Vaccination of the chickens with 1000-2500 PFU MDV-Kekava 56 which had undergone  73 a94 passages in CEF culture produced resistance to Marek's disease. Among the vaccinated chickens 20 out of 113 had Marek's disease whereas in the control group 74 out of 122 were observed to develop the disease. Among the chickens vaccinated with MDV, 3-4% developed the disease. Possible causes of the disease in this group of chickens are discussed."}
{"id": "PMID:200033", "title": "[Gestagen therapy in bladderneck adenoma. III. Clinicochemical findings and course controls in patients with bladderneck adenomas under gestagen therapy].", "content": "It is reported on clinico-chemical examinations in 30 carriers of adenomas, who underwent a gestagen therapy lasting 3 months. The treatment was performed in group I in 15 patients with progesterone depot and in group II with depostate. After the end of the treatment in group I an increase of the content of the sodium ions was found. The infections of the urinary tract improved. Neither in negative sense nor in positive sense an influence of the therapy on the other examination parameters was found.", "contents": "[Gestagen therapy in bladderneck adenoma. III. Clinicochemical findings and course controls in patients with bladderneck adenomas under gestagen therapy]. It is reported on clinico-chemical examinations in 30 carriers of adenomas, who underwent a gestagen therapy lasting 3 months. The treatment was performed in group I in 15 patients with progesterone depot and in group II with depostate. After the end of the treatment in group I an increase of the content of the sodium ions was found. The infections of the urinary tract improved. Neither in negative sense nor in positive sense an influence of the therapy on the other examination parameters was found."}
{"id": "PMID:200034", "title": "[The rhagocyte (author's transl)].", "content": "The \"rhagocyte\" (Delbarre) was defined with the aid of own results and results from the literature as an unity of structure and function of phagocytic cells in synovial fluids. Rhagocytes are an ubiquitous phenomenon in most cases of inflammation in joints detectable with nonspecific methods and are not a specific sign for the diagnosis of rheumatoid arthritis. The inclusion bodies of rhagocytes were demonstrated as immunoglobulin complexes with fixation of complement (IgG/IgM/C) by means of the immunofluorescence technique. In these specific preparations the rhagocyte has an importance as rheumatoid arthritis cell (R.A. cell) as defined by Hollander. --A definition of the rhagocyte and a description of histochemical results is given in a synopsis of characteristical properties of inclusion body cells. Moreover, a representation of the morphogenesis and value of the rhagocytes in a concept of the pathogenesis of rheumatoid arthritis, the in vitro and in vivo reproduction of rhagocytes and its value for the diagnosis in diseases of joints is given.", "contents": "[The rhagocyte (author's transl)]. The \"rhagocyte\" (Delbarre) was defined with the aid of own results and results from the literature as an unity of structure and function of phagocytic cells in synovial fluids. Rhagocytes are an ubiquitous phenomenon in most cases of inflammation in joints detectable with nonspecific methods and are not a specific sign for the diagnosis of rheumatoid arthritis. The inclusion bodies of rhagocytes were demonstrated as immunoglobulin complexes with fixation of complement (IgG/IgM/C) by means of the immunofluorescence technique. In these specific preparations the rhagocyte has an importance as rheumatoid arthritis cell (R.A. cell) as defined by Hollander. --A definition of the rhagocyte and a description of histochemical results is given in a synopsis of characteristical properties of inclusion body cells. Moreover, a representation of the morphogenesis and value of the rhagocytes in a concept of the pathogenesis of rheumatoid arthritis, the in vitro and in vivo reproduction of rhagocytes and its value for the diagnosis in diseases of joints is given."}
{"id": "PMID:200031", "title": "[Effect of deprivation of the \"rapid\" phase of sleep on self stimulation of the hypothalamus and septum in white rats].", "content": "26 rats with bipolar electrodes in lateral hypothalamic and septal areas were learned to press the bar for electrical stimulation of the brain (monopolar square pulses, 0.1 msec, 100 cps, train length 250 msec). After stabilization of self-stimulation (SS) responses, the animals were deprived of rapid eye movement sleep (REM) for up to 4 days by confinement to a small platform surrounded by water. The rats were allowed to SS for 40 min per day during and after REM deprivation up to 1 month. It was found that REM deprivation strongly increased hypothalamic SS rates but failed to change SS thresholds. As to the septal SS, its rate either increased, with threshold unchanged or lowered (1st type), or remained steady (2nd type), or decreased, with threshold unchanged or risen. In most cases the deprivation led to alteration in the shape of SS rate/intensity curve, which remained during the whole experimental period (1 month).", "contents": "[Effect of deprivation of the \"rapid\" phase of sleep on self stimulation of the hypothalamus and septum in white rats]. 26 rats with bipolar electrodes in lateral hypothalamic and septal areas were learned to press the bar for electrical stimulation of the brain (monopolar square pulses, 0.1 msec, 100 cps, train length 250 msec). After stabilization of self-stimulation (SS) responses, the animals were deprived of rapid eye movement sleep (REM) for up to 4 days by confinement to a small platform surrounded by water. The rats were allowed to SS for 40 min per day during and after REM deprivation up to 1 month. It was found that REM deprivation strongly increased hypothalamic SS rates but failed to change SS thresholds. As to the septal SS, its rate either increased, with threshold unchanged or lowered (1st type), or remained steady (2nd type), or decreased, with threshold unchanged or risen. In most cases the deprivation led to alteration in the shape of SS rate/intensity curve, which remained during the whole experimental period (1 month)."}
{"id": "PMID:200035", "title": "[Luteoma of the ovary during pregnancy (author's transl)].", "content": "The tumor of lutein cells of the ovary during pregnancy was first described by Sternberg (1963) as \"luteoma of pregnancy\". Up to 1973/74 66 cases were published. This benign tumor occurring only during pregnancy probably arises under stimulation of chorionic gonadotropin and may cause a virilization of the mother and female infant. After birth the ovarian tumors regress spontaneouly. Lutein cell tumors are usally discovered incidentally at laparotomy (cesarean section) in late pregnancy  and require no radical surgical treatment. The feature of these tumors and some related questions are discussed on the basis of on own observation being, to our knowledge, the first case of this type in Central Europe.", "contents": "[Luteoma of the ovary during pregnancy (author's transl)]. The tumor of lutein cells of the ovary during pregnancy was first described by Sternberg (1963) as \"luteoma of pregnancy\". Up to 1973/74 66 cases were published. This benign tumor occurring only during pregnancy probably arises under stimulation of chorionic gonadotropin and may cause a virilization of the mother and female infant. After birth the ovarian tumors regress spontaneouly. Lutein cell tumors are usally discovered incidentally at laparotomy (cesarean section) in late pregnancy  and require no radical surgical treatment. The feature of these tumors and some related questions are discussed on the basis of on own observation being, to our knowledge, the first case of this type in Central Europe."}
{"id": "PMID:200032", "title": "[Disintegration of enzymatically pretreated cartilage after subcutaneous implantation].", "content": "The influence of previous digestion  of cartilage proteoglycans and collagen on cartilage resorption in implants was studied. After implantation for 1, 2, 3, and 4 weeks the morphology of the implants was studied by light microscopy. It was found that enzymatic treatment of cartilage with hyaluronidase, collagenase as well as the combination of both enzymes slightly increased the resorption by granulation tissue. From these studies it can be concluded, that cartilage depletion of proteoglycans facilitates cartilage degradation, however it is not the only reason for the severe cartilage destruction seen in arthritic joints.", "contents": "[Disintegration of enzymatically pretreated cartilage after subcutaneous implantation]. The influence of previous digestion  of cartilage proteoglycans and collagen on cartilage resorption in implants was studied. After implantation for 1, 2, 3, and 4 weeks the morphology of the implants was studied by light microscopy. It was found that enzymatic treatment of cartilage with hyaluronidase, collagenase as well as the combination of both enzymes slightly increased the resorption by granulation tissue. From these studies it can be concluded, that cartilage depletion of proteoglycans facilitates cartilage degradation, however it is not the only reason for the severe cartilage destruction seen in arthritic joints."}
{"id": "PMID:200036", "title": "[Core and coat of the hepatitis b-virus and cytoplasmic viruslike particles in chronic hepatitis. An electron microscopic study (author's transl)].", "content": "In the second liver biopsy material of a seropositive patient receiving immunosuppressive therapy (Corticosteroid + Imuran) for chronic active hepatitis (CAH), intranuclear, ring-shaped, 20--25 nm in diameter non-coated particles (core) of liver cells and intracisternal filaments, 23 nm in diameter (coat) of the soft ER in the \"ground-glass\" hepatocytes were demonstrated by electron microscopy. Core-particles in the cytoplasm were seen occasionally. Dane-particles could not be visualized. Cytoplasmic spherical and ring-shaped virus-like structures (circ. 80 nm in diameter) different from B-virus components and Dane-particle were also found (second virus-infection?). The role of immuno-suppression in the appaerance of viral structures is considered because such particles could not be detected in the first biopsy before therapy when CAH and antigenaemia were already present.", "contents": "[Core and coat of the hepatitis b-virus and cytoplasmic viruslike particles in chronic hepatitis. An electron microscopic study (author's transl)]. In the second liver biopsy material of a seropositive patient receiving immunosuppressive therapy (Corticosteroid + Imuran) for chronic active hepatitis (CAH), intranuclear, ring-shaped, 20--25 nm in diameter non-coated particles (core) of liver cells and intracisternal filaments, 23 nm in diameter (coat) of the soft ER in the \"ground-glass\" hepatocytes were demonstrated by electron microscopy. Core-particles in the cytoplasm were seen occasionally. Dane-particles could not be visualized. Cytoplasmic spherical and ring-shaped virus-like structures (circ. 80 nm in diameter) different from B-virus components and Dane-particle were also found (second virus-infection?). The role of immuno-suppression in the appaerance of viral structures is considered because such particles could not be detected in the first biopsy before therapy when CAH and antigenaemia were already present."}
{"id": "PMID:200030", "title": "[Cellular mechanisms of conditioned reflex integration].", "content": "The paper deals with the formation of cellular mechanisms of integration in the course of conditioned reflex elaboration. Primary integration consists in an interaction between the effects of the conditioned (CS) and unconditioned (US) stimuli on neurons, which leads to a stable connection between them. The subsequent, final integration consists in the joining up of these cells into special populations with common functional properties in relation to the paired stimuli. Primary integration is achieved either by the mechanism of addition of the elaborated reaction to the CS to the response to the US, or by joining an adequate reaction to the CS of the elaborated response to the US. The final integration is apparently achieved by the mechanisms of transmition from one neuron to another of the formed connection between the paired stimuli along one path common for the association as a whole.", "contents": "[Cellular mechanisms of conditioned reflex integration]. The paper deals with the formation of cellular mechanisms of integration in the course of conditioned reflex elaboration. Primary integration consists in an interaction between the effects of the conditioned (CS) and unconditioned (US) stimuli on neurons, which leads to a stable connection between them. The subsequent, final integration consists in the joining up of these cells into special populations with common functional properties in relation to the paired stimuli. Primary integration is achieved either by the mechanism of addition of the elaborated reaction to the CS to the response to the US, or by joining an adequate reaction to the CS of the elaborated response to the US. The final integration is apparently achieved by the mechanisms of transmition from one neuron to another of the formed connection between the paired stimuli along one path common for the association as a whole."}
{"id": "PMID:200037", "title": "An epidemiological study on paramyxovirus antibody titers in multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.", "content": "The present epidemiological study concerned and evaluation of the level of measles antibodies (hemagglutination inhibition (HI) assay) and para-influenza-1 (Sendai) antibodies (complement fixation (CF) test) in serum of 107 control individuals (38 women), 176 multiple sclerosis (MS) patients (93 women), 717 relatives to MS patients (361 women), 9 patients with systemic lupus erythematosus (SLE) (all women), 46 relatives to SLE patients (28 women), 57 patients with rheumatoid arthritis (RA) (37 women), and 143 relatives to RA patients (85 women). In MS and their relatives the HI titer value was significantly raised and the CF titer only insignificantly increased. In SLE the HI titers were insignificantly raised but the CF values significantly decreased. In RA HI values were insignificatly raised, but the CF values were significantly decreased among females lacking rheumatoid factor in serum. In the individuals under study, HI values did not correlate with CF values. In MS two groups of patients could be treated, i.e. one group with raised HI values and one with normal distribution of titers. The data obtained are discussed in light of the theory, that all three disease entities may be \"Slow Virus Diseases\".", "contents": "An epidemiological study on paramyxovirus antibody titers in multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. The present epidemiological study concerned and evaluation of the level of measles antibodies (hemagglutination inhibition (HI) assay) and para-influenza-1 (Sendai) antibodies (complement fixation (CF) test) in serum of 107 control individuals (38 women), 176 multiple sclerosis (MS) patients (93 women), 717 relatives to MS patients (361 women), 9 patients with systemic lupus erythematosus (SLE) (all women), 46 relatives to SLE patients (28 women), 57 patients with rheumatoid arthritis (RA) (37 women), and 143 relatives to RA patients (85 women). In MS and their relatives the HI titer value was significantly raised and the CF titer only insignificantly increased. In SLE the HI titers were insignificantly raised but the CF values significantly decreased. In RA HI values were insignificatly raised, but the CF values were significantly decreased among females lacking rheumatoid factor in serum. In the individuals under study, HI values did not correlate with CF values. In MS two groups of patients could be treated, i.e. one group with raised HI values and one with normal distribution of titers. The data obtained are discussed in light of the theory, that all three disease entities may be \"Slow Virus Diseases\"."}
{"id": "PMID:200039", "title": "[Biologic-economic study of processes for cultivating Clostridium perfringens. II. Comparison of the effectiveness of actual and predicted processes for cultivating microorganisms].", "content": "The authors analyzed the efficacy of actual and prognosticated processes of Cl. perfringens, type A, cultivation: periodic, semicontinuous, continuous, and combined monocyclic. Comparative study permitted to choose the economically optimal processes, without any expenditure for their realization. Monocyclic combined process which could provide a great amount of active toxin at short periods proved to be the most advantageous among the cultivation processes studied.", "contents": "[Biologic-economic study of processes for cultivating Clostridium perfringens. II. Comparison of the effectiveness of actual and predicted processes for cultivating microorganisms]. The authors analyzed the efficacy of actual and prognosticated processes of Cl. perfringens, type A, cultivation: periodic, semicontinuous, continuous, and combined monocyclic. Comparative study permitted to choose the economically optimal processes, without any expenditure for their realization. Monocyclic combined process which could provide a great amount of active toxin at short periods proved to be the most advantageous among the cultivation processes studied."}
{"id": "PMID:200042", "title": "GnRH action in rat anterior pituitary gland: regulation of protein, glycoprotein and LH synthesis.", "content": "The effect of synthetic GnRH on the synthesis of proteins and glycoproteins in the anterior pituitary and in vitro release of LH into the medium was studied. A maximal dose (25 ng/ml) of of synthetic GnRH caused optimum release of radioimmunoassayable LH into the medium after 2 h of incubation. A concomitant increase in cyclic AMP accumulation in the tissue and LH in the incubation medium was also observed under the influence of GnRH during different periods of incubation time. Incubation of the rat anterior pituitary with GnRH stimulated the incorporation of [3H] proline into acid precipitable proteins in a time- and dose-dependent manner, similar to radioimmunoassayable LH released into the medium. Similar results were obtained when pituitary was incubated with dibutyryl cyclic AMP. LH, in addition, enhanced the incorporation of [3H] glucosamine and [3H] amino acids mixture into acid-precipitable proteins suggesting that proteins including glycoproteins are synthesized by the rat anterior pituitary under the influence of GnRH. Approximately 10% of the radioactivity associated with proteins comigrated with radioimmunoassayable LH on the gels. GnRH also enhanced the incorporation of [3H] glucosamine and [3H] amino acid mixture into immunoprecipitable LH. The GnRH-induced incorporation of [3H] proline into anterior pituitary proteins was abolished by specific translation inhibitors.", "contents": "GnRH action in rat anterior pituitary gland: regulation of protein, glycoprotein and LH synthesis. The effect of synthetic GnRH on the synthesis of proteins and glycoproteins in the anterior pituitary and in vitro release of LH into the medium was studied. A maximal dose (25 ng/ml) of of synthetic GnRH caused optimum release of radioimmunoassayable LH into the medium after 2 h of incubation. A concomitant increase in cyclic AMP accumulation in the tissue and LH in the incubation medium was also observed under the influence of GnRH during different periods of incubation time. Incubation of the rat anterior pituitary with GnRH stimulated the incorporation of [3H] proline into acid precipitable proteins in a time- and dose-dependent manner, similar to radioimmunoassayable LH released into the medium. Similar results were obtained when pituitary was incubated with dibutyryl cyclic AMP. LH, in addition, enhanced the incorporation of [3H] glucosamine and [3H] amino acids mixture into acid-precipitable proteins suggesting that proteins including glycoproteins are synthesized by the rat anterior pituitary under the influence of GnRH. Approximately 10% of the radioactivity associated with proteins comigrated with radioimmunoassayable LH on the gels. GnRH also enhanced the incorporation of [3H] glucosamine and [3H] amino acid mixture into immunoprecipitable LH. The GnRH-induced incorporation of [3H] proline into anterior pituitary proteins was abolished by specific translation inhibitors."}
{"id": "PMID:200043", "title": "Ionic effects on the uptake of chloromercuribenzene-p-sulphonic acid by pancreatic islets.", "content": "Effects of inorganic ions on the uptake of chloromercuribenzene-p-sulphonic acid (CMBS) were studied in microdissected pancreatic islets of non-inbred ob/ob-mice. Na2SO4 stimulated the total islet cell uptake of CMBS but decreased the amount of CMBS remaining in islets after brief washing with L-cysteine. CaCl2 stimulated both the total and the cysteine-nondisplaceable uptake; the stimulatory effect of CaCl2 on the cysteine-non-displaceable CMBS uptake was counteracted by Na2SO4. NaCl, KCl or choline chloride had no significant effect on the total islet cell uptake of CMBS, whereas LiCl was stimulatory. It is concluded that beta-cells resemble erythrocytes in having a permeation path for CMBS that is inhibited by SO4(2-). By analogy with existing models of the erythrocyte membrane, it is suggested that the SO4(2-) sensitive path leads to sulphydryl groups controlling monovalent cationic permeability in beta-cells.", "contents": "Ionic effects on the uptake of chloromercuribenzene-p-sulphonic acid by pancreatic islets. Effects of inorganic ions on the uptake of chloromercuribenzene-p-sulphonic acid (CMBS) were studied in microdissected pancreatic islets of non-inbred ob/ob-mice. Na2SO4 stimulated the total islet cell uptake of CMBS but decreased the amount of CMBS remaining in islets after brief washing with L-cysteine. CaCl2 stimulated both the total and the cysteine-nondisplaceable uptake; the stimulatory effect of CaCl2 on the cysteine-non-displaceable CMBS uptake was counteracted by Na2SO4. NaCl, KCl or choline chloride had no significant effect on the total islet cell uptake of CMBS, whereas LiCl was stimulatory. It is concluded that beta-cells resemble erythrocytes in having a permeation path for CMBS that is inhibited by SO4(2-). By analogy with existing models of the erythrocyte membrane, it is suggested that the SO4(2-) sensitive path leads to sulphydryl groups controlling monovalent cationic permeability in beta-cells."}
{"id": "PMID:200040", "title": "[The so-called minimal cancers of the breast (author's transl)].", "content": "In situ lobular carcinoma, intraductal carcinoma and papilliferous non-invasive carcinoma are three non-invading cancers that present clinically as the other malignant tumors of the breast. Between January 1, 1973 and August 31, 1976, ten patients were operated at the institut Bordet for such tumors. Surgical treatment varied between radical mastectomy according to Madden and partial mammectomy. Follow-up reveals no recurrence over periods extending from zero to three years. The choice of treatment depends on the histology and the probability of evolution of the actual cancer.", "contents": "[The so-called minimal cancers of the breast (author's transl)]. In situ lobular carcinoma, intraductal carcinoma and papilliferous non-invasive carcinoma are three non-invading cancers that present clinically as the other malignant tumors of the breast. Between January 1, 1973 and August 31, 1976, ten patients were operated at the institut Bordet for such tumors. Surgical treatment varied between radical mastectomy according to Madden and partial mammectomy. Follow-up reveals no recurrence over periods extending from zero to three years. The choice of treatment depends on the histology and the probability of evolution of the actual cancer."}
{"id": "PMID:200044", "title": "Insulin stimulation tests in pituitary dependent Cushing's syndrome after complete adrenalectomy.", "content": "The present study shows that in a group of 6 euadrenal patients, previously treated by complete adrenalectomy for pituitary dependent Cushing's syndrome, the stress stimulus of insulin induced hypoglycaemia is followed by a plasma ACTH response which is of similar magnitude as the response obtained with lysin-vasopressin. Both observations indicate that the central nervous system-pituitary axis is basically normal in pituitary dependent Cushing's syndrome as assessed by insulin induced hypoglycaemia. It is concluded that non-responsiveness of the pituitary-adrenocortical system to insulin induced hypoglycaemia in untreated patients with pituitary dependent Cushing's syndrome does not represent a fundamental defect of the stress mechanism, but is due to hypercorticism per se.", "contents": "Insulin stimulation tests in pituitary dependent Cushing's syndrome after complete adrenalectomy. The present study shows that in a group of 6 euadrenal patients, previously treated by complete adrenalectomy for pituitary dependent Cushing's syndrome, the stress stimulus of insulin induced hypoglycaemia is followed by a plasma ACTH response which is of similar magnitude as the response obtained with lysin-vasopressin. Both observations indicate that the central nervous system-pituitary axis is basically normal in pituitary dependent Cushing's syndrome as assessed by insulin induced hypoglycaemia. It is concluded that non-responsiveness of the pituitary-adrenocortical system to insulin induced hypoglycaemia in untreated patients with pituitary dependent Cushing's syndrome does not represent a fundamental defect of the stress mechanism, but is due to hypercorticism per se."}
{"id": "PMID:200046", "title": "Hypophysis and function of pancreatic islets. IV. Effect of treatment with growth hormone and corticotrophin on insulin secretion and biosynthesis in isolated pancreatic islets of normal rats.", "content": "The effects of the recognized diabetogenic hormones, growth hormone and ACTH, administered in vivo, on (pro-)insulin biosynthesis and secretion in isolated islets of normal rats were studied. Rats were treated with these hormones for 4 weeks. Afterwards, their collagenase-isolated islets were incubated with [3H]leucine for 3 h. (Pro-)Insulin biosynthesis was estimated for the incorporation data into islet protein fractions. Islets of treated rats released significantly more insulin and incorporated significantly less [3H]leucine into proinsulin and insulin compared with controls when tested at 100 mg glucose/100 ml. At 200 mg glucose/100 ml, no significant differences were found. The findings demonstrate an impact of these hormones on the B-cells derived from normal pancreas of intact rats. The alterations are, however, not very pronounced and can be easily compensated under a strong glucose stimulus. It appears that the mechanisms for (pro-)insulin biosynthesis and release in rats are more resistant against the diabetogenic actions of pituitary hormones than in other species.", "contents": "Hypophysis and function of pancreatic islets. IV. Effect of treatment with growth hormone and corticotrophin on insulin secretion and biosynthesis in isolated pancreatic islets of normal rats. The effects of the recognized diabetogenic hormones, growth hormone and ACTH, administered in vivo, on (pro-)insulin biosynthesis and secretion in isolated islets of normal rats were studied. Rats were treated with these hormones for 4 weeks. Afterwards, their collagenase-isolated islets were incubated with [3H]leucine for 3 h. (Pro-)Insulin biosynthesis was estimated for the incorporation data into islet protein fractions. Islets of treated rats released significantly more insulin and incorporated significantly less [3H]leucine into proinsulin and insulin compared with controls when tested at 100 mg glucose/100 ml. At 200 mg glucose/100 ml, no significant differences were found. The findings demonstrate an impact of these hormones on the B-cells derived from normal pancreas of intact rats. The alterations are, however, not very pronounced and can be easily compensated under a strong glucose stimulus. It appears that the mechanisms for (pro-)insulin biosynthesis and release in rats are more resistant against the diabetogenic actions of pituitary hormones than in other species."}
{"id": "PMID:200047", "title": "Longitudinal study of the behaviour of certain hormonal parameters in women undergoing treatment with cyproterone acetate.", "content": "A study has been made of the behaviour of certain hormonal parameters (LH, FSH, PRL, HGH, ACTH, cortisol and testosterone) in five women aged from 17 to 28 years, during two successive menstrual cycles, the first under basal conditions and the second while under treatment with cyproterone acetate (CPA) 100 mg/day), given from the fifth to the twenty-fifth day of the cycle. On the first day of the initial cycle and the twenty-ninth day of the second cycle, the secretion of gonadotropins, prolactin, and somatotropin were measured before and after stimulation with GnRH (50 microgram, i.v.), sulpiride (200 mg, i.m.) or insulin (0.1 U/kg). During treatment with CPA the ovulatory peak of LH was abolished, with a reduction in the levels of gonadotropin and testosterone. No changes were observed for PRL, HGH, ACTH or cortisol. The study of the pituitary reserves showed a reduced response of LH but not of FSH to GnRH. There were no changes in the response of PRL and HGH to stimulation. The data obtained confirm the inhibitory effect of CPA on gonadotropin and testosterone secretion, while the other parameters studied did not vary significantly.", "contents": "Longitudinal study of the behaviour of certain hormonal parameters in women undergoing treatment with cyproterone acetate. A study has been made of the behaviour of certain hormonal parameters (LH, FSH, PRL, HGH, ACTH, cortisol and testosterone) in five women aged from 17 to 28 years, during two successive menstrual cycles, the first under basal conditions and the second while under treatment with cyproterone acetate (CPA) 100 mg/day), given from the fifth to the twenty-fifth day of the cycle. On the first day of the initial cycle and the twenty-ninth day of the second cycle, the secretion of gonadotropins, prolactin, and somatotropin were measured before and after stimulation with GnRH (50 microgram, i.v.), sulpiride (200 mg, i.m.) or insulin (0.1 U/kg). During treatment with CPA the ovulatory peak of LH was abolished, with a reduction in the levels of gonadotropin and testosterone. No changes were observed for PRL, HGH, ACTH or cortisol. The study of the pituitary reserves showed a reduced response of LH but not of FSH to GnRH. There were no changes in the response of PRL and HGH to stimulation. The data obtained confirm the inhibitory effect of CPA on gonadotropin and testosterone secretion, while the other parameters studied did not vary significantly."}
{"id": "PMID:200053", "title": "Content and composition of urinary glycosaminoglycans in the patients with myoclonus epilepsy with and without Lafora bodies.", "content": "Content, composition and molecular weight distribution of the urinary glycosaminoglycans (GAG) were determined in five patients with progressive myoclonus epilepsy (PME). In one patient (Family B) this syndrome was associated with cerebral Lafora bodies and in four siblings of Family A, no Lafora bodies were present in brain biopsy. Only one of the five patients had a moderate increase of urinary GAG excretion as expressed by 24-h output or creatinine. The heparan sulfate component of the GAG was moderately increased in two other patients. The molecular weight distribution of the urinary GAG was normal. The results do not support the contention that urinary GAG excretion is abnormal in PME. Among nine lysosomal enzymes in leucocytes, only the activity of alpha-mannosidase was increased 3-fold in the four siblings.", "contents": "Content and composition of urinary glycosaminoglycans in the patients with myoclonus epilepsy with and without Lafora bodies. Content, composition and molecular weight distribution of the urinary glycosaminoglycans (GAG) were determined in five patients with progressive myoclonus epilepsy (PME). In one patient (Family B) this syndrome was associated with cerebral Lafora bodies and in four siblings of Family A, no Lafora bodies were present in brain biopsy. Only one of the five patients had a moderate increase of urinary GAG excretion as expressed by 24-h output or creatinine. The heparan sulfate component of the GAG was moderately increased in two other patients. The molecular weight distribution of the urinary GAG was normal. The results do not support the contention that urinary GAG excretion is abnormal in PME. Among nine lysosomal enzymes in leucocytes, only the activity of alpha-mannosidase was increased 3-fold in the four siblings."}
{"id": "PMID:200054", "title": "Cerebral calcinosis with late onset encephalopathy. Unusual type of pseudo-pseudohypoparathyreoidism.", "content": "A family from Western Norway is described in which 5 out of 9 members in one generation developed a progressive encephalopathy in middle life. Massive, symmetrical calcifications located in basal ganglia, dentate nuclei and cerebral sulci of the brain were seen on roentgenograms of the skull. All affected members exhibited a clinical syndrome which included mental deterioration, extrapyramidal motor deficit, cerebellar ataxia and tremor. The biochemical investigation showed normal serum calcium and phosphorous and concentration of immunoreactive parathyroid hormone was normal. The Ellsworth-Howard test with exogenously administered parathyroid extract revealed a subnormal phosphorous diuresis while urinary excretion of cyclic AMP was normal. Thus, the defect appears to be an insufficient intracellular response to cyclic AMP. The late onset of symptoms is compatible with the slight disturbance in calcium-phosphorous metabolism we have demonstrated. The family probably represents an unusual type of pseudo-pseudohypoparathyroidism of which only one other family has been reported earlier. The investigations and pedigree analysis of the present kindred is suggestive of an autosomal recessive inheritance of the disorder.", "contents": "Cerebral calcinosis with late onset encephalopathy. Unusual type of pseudo-pseudohypoparathyreoidism. A family from Western Norway is described in which 5 out of 9 members in one generation developed a progressive encephalopathy in middle life. Massive, symmetrical calcifications located in basal ganglia, dentate nuclei and cerebral sulci of the brain were seen on roentgenograms of the skull. All affected members exhibited a clinical syndrome which included mental deterioration, extrapyramidal motor deficit, cerebellar ataxia and tremor. The biochemical investigation showed normal serum calcium and phosphorous and concentration of immunoreactive parathyroid hormone was normal. The Ellsworth-Howard test with exogenously administered parathyroid extract revealed a subnormal phosphorous diuresis while urinary excretion of cyclic AMP was normal. Thus, the defect appears to be an insufficient intracellular response to cyclic AMP. The late onset of symptoms is compatible with the slight disturbance in calcium-phosphorous metabolism we have demonstrated. The family probably represents an unusual type of pseudo-pseudohypoparathyroidism of which only one other family has been reported earlier. The investigations and pedigree analysis of the present kindred is suggestive of an autosomal recessive inheritance of the disorder."}
{"id": "PMID:200051", "title": "[Preliminary observations on the results of treating malignant lymphoma with Lycurim].", "content": "The authors gave Lycurim to 30 patients with malignant lymphoma (LLC--12 cases, Hodgkin's disease - 15 cases, reticulosarcoma - 2 cases and lymphosarcoma - 1 case). The patients were divided into three groups. Group I received only Lycurim, group II - Lycurim and prednisone, group III - Lycurim and Solcoseryl. Significant improvement was observed in 22 patients, with complete remission in 5 cases and partial in 17 cases. Leucopenia and thrombocytopenia precluding treatment were never observed in cases treated simultaneously with prednisone or Solcoseryl. The authors believe that the proportion of remissions may be increased combining Lycurim with vincristine, procarbazine and glycocorticosteroids (LOP or LOPP).", "contents": "[Preliminary observations on the results of treating malignant lymphoma with Lycurim]. The authors gave Lycurim to 30 patients with malignant lymphoma (LLC--12 cases, Hodgkin's disease - 15 cases, reticulosarcoma - 2 cases and lymphosarcoma - 1 case). The patients were divided into three groups. Group I received only Lycurim, group II - Lycurim and prednisone, group III - Lycurim and Solcoseryl. Significant improvement was observed in 22 patients, with complete remission in 5 cases and partial in 17 cases. Leucopenia and thrombocytopenia precluding treatment were never observed in cases treated simultaneously with prednisone or Solcoseryl. The authors believe that the proportion of remissions may be increased combining Lycurim with vincristine, procarbazine and glycocorticosteroids (LOP or LOPP)."}
{"id": "PMID:200056", "title": "[Current therapy of juvenile nasopharyngeal angiofibroma].", "content": "The nasopharyngeal angiofibrom continues sometimes to challenge the otolaryngologists because of the difficult radical surgery owing to the deep anchorage of the tumor in the base of the skull. In these cases, when possible, the embolization followed by surgery or the radiotherapy are the two better treatments. Without embolization, radiotherapy must be preferred because of the life threatening surgery that cannot eradicate the tumor.", "contents": "[Current therapy of juvenile nasopharyngeal angiofibroma]. The nasopharyngeal angiofibrom continues sometimes to challenge the otolaryngologists because of the difficult radical surgery owing to the deep anchorage of the tumor in the base of the skull. In these cases, when possible, the embolization followed by surgery or the radiotherapy are the two better treatments. Without embolization, radiotherapy must be preferred because of the life threatening surgery that cannot eradicate the tumor."}
{"id": "PMID:200057", "title": "Hepatocellular carcinoma and chronic persistent hepatitis.", "content": "The morphologic type of cirrhosis that is followed most frequently by hepatocellular carcinoma is posthepatitic cirrhosis. Furthermore, HB AG is detected in a high rate among cases with hepatocellular carcinoma suggesting the intimate causal relationship between hepatitis b virus and hepatocellular carcinoma. It has been considered that hepatocellular carcinoma might develop during destruction and regeneration of fully developed liver cirrhosis. However, hepatocellular carcinoma is combined with not only liver cirrhosis but also with mild liver fibrosis. An attempt was made to determine HBs Ag in the liver tissue of liver fibrosis with hepatocellular carcinoma. HBs Ag was found in non-cancerous liver tissue of 40 percent of those cases. Therefore, it may be concluded that, at least some of those fibrosis is caused by chronic viral hepatitis and hepatocellular carcinoma may develop not only on posthepatitic cirrhosis but also on chronic persistent hepatitis. This evidence also suggests the carcinogenicity of hepatitis B virus.", "contents": "Hepatocellular carcinoma and chronic persistent hepatitis. The morphologic type of cirrhosis that is followed most frequently by hepatocellular carcinoma is posthepatitic cirrhosis. Furthermore, HB AG is detected in a high rate among cases with hepatocellular carcinoma suggesting the intimate causal relationship between hepatitis b virus and hepatocellular carcinoma. It has been considered that hepatocellular carcinoma might develop during destruction and regeneration of fully developed liver cirrhosis. However, hepatocellular carcinoma is combined with not only liver cirrhosis but also with mild liver fibrosis. An attempt was made to determine HBs Ag in the liver tissue of liver fibrosis with hepatocellular carcinoma. HBs Ag was found in non-cancerous liver tissue of 40 percent of those cases. Therefore, it may be concluded that, at least some of those fibrosis is caused by chronic viral hepatitis and hepatocellular carcinoma may develop not only on posthepatitic cirrhosis but also on chronic persistent hepatitis. This evidence also suggests the carcinogenicity of hepatitis B virus."}
{"id": "PMID:200058", "title": "Character of the tumors developing in young hamsters by the mixed cell transplantation of para-adeno-virus 12 and SV40 tumors-the similarity to the tumors induced by para-adenovirus 7.", "content": "Two mixtures of either allogeneic PARA-adenovirus 12 tumor cells or adenovirus (Adeno) 12 tumor cells and SV40 tumor cells in an equal number of 1 multiplied by 10(7) cells were transplanted subcutaneously at two sites of 10 young hamsters. The former two tumor cells were transplantable in nearly half of the transplants and the latter tumor cells in all of the transplants. By the mixture of PARA-Adeno 12 and SV40 tumor cells, 10 tumors were grown, 7 of which were mixed with Adeno and SV40 types and 3 were solely SV40 type. The other 10 tumors produced by the mixture of Adeno 12 and SV40 tumor cells revealed SV40 type only. Morphologically, Adeno type resembled the tumor induced by Adeno, and SV40 type by SV40. The results suggest that the existence of SV40 genetic information in Adeno type tumor cells is indispensable to the formation of mixed tumor in allogeneic tumor cell system. The similarity between the tumors developed by the mixed cell transplantation and those induced by PARA-adeno 7 was discussed both viro-immunologically and morphologically.", "contents": "Character of the tumors developing in young hamsters by the mixed cell transplantation of para-adeno-virus 12 and SV40 tumors-the similarity to the tumors induced by para-adenovirus 7. Two mixtures of either allogeneic PARA-adenovirus 12 tumor cells or adenovirus (Adeno) 12 tumor cells and SV40 tumor cells in an equal number of 1 multiplied by 10(7) cells were transplanted subcutaneously at two sites of 10 young hamsters. The former two tumor cells were transplantable in nearly half of the transplants and the latter tumor cells in all of the transplants. By the mixture of PARA-Adeno 12 and SV40 tumor cells, 10 tumors were grown, 7 of which were mixed with Adeno and SV40 types and 3 were solely SV40 type. The other 10 tumors produced by the mixture of Adeno 12 and SV40 tumor cells revealed SV40 type only. Morphologically, Adeno type resembled the tumor induced by Adeno, and SV40 type by SV40. The results suggest that the existence of SV40 genetic information in Adeno type tumor cells is indispensable to the formation of mixed tumor in allogeneic tumor cell system. The similarity between the tumors developed by the mixed cell transplantation and those induced by PARA-adeno 7 was discussed both viro-immunologically and morphologically."}
{"id": "PMID:200059", "title": "Bronchial carcinoid accompanied by thyroid adenomas and adrenal adenomas.", "content": "A large tumor massively occupying the left pleural cavity had the findings of both typical carcinoid and onococytoma which were thought to be of bronchogenic origin. The ultrastructural observation of the tumor revealed a mixture of rod-shaped granules in addition to usual round neurosecretory ones. In the nuclei of dark cells of the oncocytoma, a latticed or hatched structure was detected. Besides two adenomas and hyperplastic foci of large acidophilic cells in the thyroid, a black adenoma and cortical adenoma in the adrenal gland, were detected. Moreover, there was an ectopic adrenal gland in the retroperitoneum. Briefly it was suggested that the bronchial carcinoid presented may be related to multiple endocrine adenomatosis.", "contents": "Bronchial carcinoid accompanied by thyroid adenomas and adrenal adenomas. A large tumor massively occupying the left pleural cavity had the findings of both typical carcinoid and onococytoma which were thought to be of bronchogenic origin. The ultrastructural observation of the tumor revealed a mixture of rod-shaped granules in addition to usual round neurosecretory ones. In the nuclei of dark cells of the oncocytoma, a latticed or hatched structure was detected. Besides two adenomas and hyperplastic foci of large acidophilic cells in the thyroid, a black adenoma and cortical adenoma in the adrenal gland, were detected. Moreover, there was an ectopic adrenal gland in the retroperitoneum. Briefly it was suggested that the bronchial carcinoid presented may be related to multiple endocrine adenomatosis."}
{"id": "PMID:200055", "title": "Labyrinthine input to the vestibular nuclei of the awake cat.", "content": "The labyrinthine input to the vestibular nuclei was investigated in 24 awake cats. Stimulus consisted of electrical shocks given through bipolar silver wire electrodes, implanted in the utricular and lateral ampullar nerves. Throughout the vestibular nuclei, single units were recorded extracellularly with glass micropipettes filled with Fast Green. The tracts of the penetrating electrodes were identified histologically. In all four nuclei units responding to both labyrinths outnumbered unilaterally responding neurones with certain differences between the individual nuclei. Excitatory as well as inhibitory responses were observed, polysynaptic being more common than mono- or disynaptic ones. No monosynaptic contralateral responses were seen. The latency distribution of contralateral responses closely mirrored that of ipsilateral responses within each nucleus. Both excitatory and inhibitory responses fell into relatively segregated populations, based upon latency distribution. This implies separate pathways for labyrinthine input to the vestibular nuclei.", "contents": "Labyrinthine input to the vestibular nuclei of the awake cat. The labyrinthine input to the vestibular nuclei was investigated in 24 awake cats. Stimulus consisted of electrical shocks given through bipolar silver wire electrodes, implanted in the utricular and lateral ampullar nerves. Throughout the vestibular nuclei, single units were recorded extracellularly with glass micropipettes filled with Fast Green. The tracts of the penetrating electrodes were identified histologically. In all four nuclei units responding to both labyrinths outnumbered unilaterally responding neurones with certain differences between the individual nuclei. Excitatory as well as inhibitory responses were observed, polysynaptic being more common than mono- or disynaptic ones. No monosynaptic contralateral responses were seen. The latency distribution of contralateral responses closely mirrored that of ipsilateral responses within each nucleus. Both excitatory and inhibitory responses fell into relatively segregated populations, based upon latency distribution. This implies separate pathways for labyrinthine input to the vestibular nuclei."}
{"id": "PMID:200060", "title": "Histological observation of the brain of Tay-Sachs disease with seizure and chronic DPH intoxication--report of an autopsy case.", "content": "The patients was a 3-year-old boy with psychomotor retardation and attacked by seizures since 8 months of age. On funduscopy, the maculla presented a cherry-red spot. Serum hexosaminidase A activities were as low as 8.2 percent. Both parents were carriers. The patient was diagnosed as classical Tay-Sachs disease by neurological examination. Diphenylhydantoin was continuously given for 2 years and 2 months till his death. Autopsy revealed swelling of the cerebrum, atrophy and sclerosis of the cerebellum, hepatomegaly and mild enlargement of the lymph nodes. Histologically, the cerebrum showed ballooned swelling of nerve cells, slight gliosis and demyelination, while cerebellar Purkinje's cells and granular cells were degenerated and disappeared. The cerebellar cortex showed small focal spongy degeneration. By electron microscopy, membranous cytoplasmic bodies were found in the nerve cells. The change of brain observed in this case were interpreted as a combined result of (i) essential change to classical Tay-Sachs disease, (ii) ischemic change due to frequently repeated seizures, (iii) chronic toxicity by long-term anticonvulsant administration.", "contents": "Histological observation of the brain of Tay-Sachs disease with seizure and chronic DPH intoxication--report of an autopsy case. The patients was a 3-year-old boy with psychomotor retardation and attacked by seizures since 8 months of age. On funduscopy, the maculla presented a cherry-red spot. Serum hexosaminidase A activities were as low as 8.2 percent. Both parents were carriers. The patient was diagnosed as classical Tay-Sachs disease by neurological examination. Diphenylhydantoin was continuously given for 2 years and 2 months till his death. Autopsy revealed swelling of the cerebrum, atrophy and sclerosis of the cerebellum, hepatomegaly and mild enlargement of the lymph nodes. Histologically, the cerebrum showed ballooned swelling of nerve cells, slight gliosis and demyelination, while cerebellar Purkinje's cells and granular cells were degenerated and disappeared. The cerebellar cortex showed small focal spongy degeneration. By electron microscopy, membranous cytoplasmic bodies were found in the nerve cells. The change of brain observed in this case were interpreted as a combined result of (i) essential change to classical Tay-Sachs disease, (ii) ischemic change due to frequently repeated seizures, (iii) chronic toxicity by long-term anticonvulsant administration."}
{"id": "PMID:200061", "title": "A new type of mucolipidosis associated with hereditary thrombocytopathy and color blindness.", "content": "Autopsy findings of a 22-year-old Japanese male who showed the symptoms of both mucopolysaccharidosis and sphingolipidosis are reported. The patient had a gargoyle-like face, bone change with cherry-red spot and absence of mucopolysacchariduria, and moreover accompanied by hereditary thrombocytopathy and color blindness. Autopsy findings were almost the same as those of mucopolysaccharidosis, histochemically and electron microscopically. Unique findings were, however, present in the hepatocytes, another inclusion containing dense fine granuloreticular structures was found electron microscopically. Some foamy cells in the lymph nodes, liver including sinusiodal cells, bone marrow and spleen contained intracytoplasmic sudanophilic substance in the form of moderate electron dense globules by electron microscopy. The outstanding finding of the enzymatic activity was the decrease of beta-galactosidase in the liver and brain.", "contents": "A new type of mucolipidosis associated with hereditary thrombocytopathy and color blindness. Autopsy findings of a 22-year-old Japanese male who showed the symptoms of both mucopolysaccharidosis and sphingolipidosis are reported. The patient had a gargoyle-like face, bone change with cherry-red spot and absence of mucopolysacchariduria, and moreover accompanied by hereditary thrombocytopathy and color blindness. Autopsy findings were almost the same as those of mucopolysaccharidosis, histochemically and electron microscopically. Unique findings were, however, present in the hepatocytes, another inclusion containing dense fine granuloreticular structures was found electron microscopically. Some foamy cells in the lymph nodes, liver including sinusiodal cells, bone marrow and spleen contained intracytoplasmic sudanophilic substance in the form of moderate electron dense globules by electron microscopy. The outstanding finding of the enzymatic activity was the decrease of beta-galactosidase in the liver and brain."}
{"id": "PMID:200063", "title": "Mechanical and metabolic effects of diazoxide in rat uterus.", "content": "Diazoxide relaxed both polarized and depolarized rat uterus. The drug also conteracted the contractions elicited by Ca2+ in a competitive manner. The relaxing effect was associated with an increase in the tissue level of cyclic AMP. This metabolic effect of diazoxide was inhibited by propranolol-treatment and in preparations from reserpinized animals, while the mechanical effects were only partially reduced. Diazoxide was also found to increase the release of tritium from preparations preloaded with [3H]-noradrenaline. It is suggested that diazoxide  may induce some of its mechanical and metabolic effects by releasing the adrenergic transmittor substance noradrenaline. An effect of diazoxide on the Ca2+-metabolism is also probable.", "contents": "Mechanical and metabolic effects of diazoxide in rat uterus. Diazoxide relaxed both polarized and depolarized rat uterus. The drug also conteracted the contractions elicited by Ca2+ in a competitive manner. The relaxing effect was associated with an increase in the tissue level of cyclic AMP. This metabolic effect of diazoxide was inhibited by propranolol-treatment and in preparations from reserpinized animals, while the mechanical effects were only partially reduced. Diazoxide was also found to increase the release of tritium from preparations preloaded with [3H]-noradrenaline. It is suggested that diazoxide  may induce some of its mechanical and metabolic effects by releasing the adrenergic transmittor substance noradrenaline. An effect of diazoxide on the Ca2+-metabolism is also probable."}
{"id": "PMID:200064", "title": "Effect of adenosine compounds (ATP, cAMP) on renin release in vitro.", "content": "Renin release by surviving canine renal cortical slices incubated media with ATP or cAMP at concentrations of 5 X 10(-5)--5 X 10(-3) M has been studied. Both adenosine compounds were significantly increasing renin release. A linear correlation was observed between their dose and the renin activity of the medium. The difference between the effects of ATP and cAMP appeared to be caused by phosphodiesterase, since the difference was eliminated if to the medium containing cAMP 5 X 10(-2) M theophylline, a phosphodiesterase inhibitor was added.", "contents": "Effect of adenosine compounds (ATP, cAMP) on renin release in vitro. Renin release by surviving canine renal cortical slices incubated media with ATP or cAMP at concentrations of 5 X 10(-5)--5 X 10(-3) M has been studied. Both adenosine compounds were significantly increasing renin release. A linear correlation was observed between their dose and the renin activity of the medium. The difference between the effects of ATP and cAMP appeared to be caused by phosphodiesterase, since the difference was eliminated if to the medium containing cAMP 5 X 10(-2) M theophylline, a phosphodiesterase inhibitor was added."}
{"id": "PMID:200065", "title": "Circadian rhythm of hypothalamo-hypophyseal-adrenal activity in the chicken.", "content": "Corticosteroid production, ACTH content in the adenohypophysis and CRF content in the median eminence were studied in vitro and in vivo in the 3-weeks-old chicken according to SAFFRAN and SCHALLY in four different parts of the day: at 6 and 12 a.m., and 6 and 12 p.m. The chicken adrenals in vitro produced only corticosterone in fluorimetrically measurable amounts, with the maximum during the day and the minimum in the evening and at night. Sensitivity to ACTH of the adrenals in vitro was higher during the day than in the evening or at night. After paper-chromatographic separation, steroid hormones equivalent to corticosterone and cortisol could be detected fluorimetrically in the plasma. The \"cortisol\" level was about 2-2.5 times higher than the corticosterone level. Plasma \"cortisol\" level displayed the peak at 6 a.m. and the minimum at 12 p.m., while corticosterone at 12 a.m. and 12 p.m., respectively. ACTH content in the adenohypophysis was lowest at 6 a.m. then increased gradually until 12 p.m. CRF level in the median eminence fell during the forenoon, was lowest at noon, to rise up to 6 p.m. and persist at a high level between 6 p.m. and 6 a.m. Thus, in the 3-week-old chicken the functioning of the hypothalamo-hypophyseal-adrenal system displays a circadian rhythm characteristic of animals showing diurnal activity.", "contents": "Circadian rhythm of hypothalamo-hypophyseal-adrenal activity in the chicken. Corticosteroid production, ACTH content in the adenohypophysis and CRF content in the median eminence were studied in vitro and in vivo in the 3-weeks-old chicken according to SAFFRAN and SCHALLY in four different parts of the day: at 6 and 12 a.m., and 6 and 12 p.m. The chicken adrenals in vitro produced only corticosterone in fluorimetrically measurable amounts, with the maximum during the day and the minimum in the evening and at night. Sensitivity to ACTH of the adrenals in vitro was higher during the day than in the evening or at night. After paper-chromatographic separation, steroid hormones equivalent to corticosterone and cortisol could be detected fluorimetrically in the plasma. The \"cortisol\" level was about 2-2.5 times higher than the corticosterone level. Plasma \"cortisol\" level displayed the peak at 6 a.m. and the minimum at 12 p.m., while corticosterone at 12 a.m. and 12 p.m., respectively. ACTH content in the adenohypophysis was lowest at 6 a.m. then increased gradually until 12 p.m. CRF level in the median eminence fell during the forenoon, was lowest at noon, to rise up to 6 p.m. and persist at a high level between 6 p.m. and 6 a.m. Thus, in the 3-week-old chicken the functioning of the hypothalamo-hypophyseal-adrenal system displays a circadian rhythm characteristic of animals showing diurnal activity."}
{"id": "PMID:200066", "title": "Seasonal rhythm in the hypothalamo-hypophyseal-adrenal function of the chicken.", "content": "The seasonal rhythm in hypothalamo-hypophyseal-adrenal function was studied in 3-week-old, meat-hybrid chickens, bred under standard conditions, CRF content in the median eminence and ACTH content in the adenohypophysis showed the maximum in February, the minimum in August, to return practically to the February level by November. Adrenal corticosterone production was maximum in February decreased by May and stayed at the low level for the further months of the year. The increase in autumn of the CRF content in the median eminence and of the ACTH content in the adenohypophysis, with unaltered corticosterone production suggests a reduced functioning of the mechanisms regulating hypothalamic release. It is assumed that the winter maximum in the activity of the corticotropic system is due to the endogenous annual rhythm.", "contents": "Seasonal rhythm in the hypothalamo-hypophyseal-adrenal function of the chicken. The seasonal rhythm in hypothalamo-hypophyseal-adrenal function was studied in 3-week-old, meat-hybrid chickens, bred under standard conditions, CRF content in the median eminence and ACTH content in the adenohypophysis showed the maximum in February, the minimum in August, to return practically to the February level by November. Adrenal corticosterone production was maximum in February decreased by May and stayed at the low level for the further months of the year. The increase in autumn of the CRF content in the median eminence and of the ACTH content in the adenohypophysis, with unaltered corticosterone production suggests a reduced functioning of the mechanisms regulating hypothalamic release. It is assumed that the winter maximum in the activity of the corticotropic system is due to the endogenous annual rhythm."}
{"id": "PMID:200067", "title": "Suppression of the excitatory adrenergic neurotransmission; a possible role of cholinergic nerves in the retractor penis muscle.", "content": "The excitatory adrenergic response to transmural nerve stimulation of the isolated retractor penis (rp) of dog, cat, horse, boar, elk, bull, ram and goat, as well as the evoked release of 3H from dog rp preloaded with 3H-noradrenaline were studied. In untreated preparations a low concentration of scopolamine could markedly increase the excitatory adrenergic response. On the contrary, physostigmine per se suppressed this response and so did acetylcholine. Scopolamine or atropine totally prevented these suppressions. They also immediately restored the suppressed responses in spite of continuous presence of physostigmine and/or acetylcholine. In the rat rp there was no suppression of the response by physostigmine. Physostigmine decreased the evoked release of 3H and this effect was counteracted by scopolamine. The rp of dog, gelding, boar, hog, bull and ram contained considerable amounts of noradrenaline and also of acetylcholine. It is suggested that one action of cholinergic nerves in the rp is muscarine suppression of the excitatory adrenergic neurotransmission.", "contents": "Suppression of the excitatory adrenergic neurotransmission; a possible role of cholinergic nerves in the retractor penis muscle. The excitatory adrenergic response to transmural nerve stimulation of the isolated retractor penis (rp) of dog, cat, horse, boar, elk, bull, ram and goat, as well as the evoked release of 3H from dog rp preloaded with 3H-noradrenaline were studied. In untreated preparations a low concentration of scopolamine could markedly increase the excitatory adrenergic response. On the contrary, physostigmine per se suppressed this response and so did acetylcholine. Scopolamine or atropine totally prevented these suppressions. They also immediately restored the suppressed responses in spite of continuous presence of physostigmine and/or acetylcholine. In the rat rp there was no suppression of the response by physostigmine. Physostigmine decreased the evoked release of 3H and this effect was counteracted by scopolamine. The rp of dog, gelding, boar, hog, bull and ram contained considerable amounts of noradrenaline and also of acetylcholine. It is suggested that one action of cholinergic nerves in the rp is muscarine suppression of the excitatory adrenergic neurotransmission."}
{"id": "PMID:200068", "title": "Frequency-dependence of 3H-noradrenaline secretion from human vasoconstrictor nerves: modification by factors interfering with alpha-or beta-adrenoceptor or prostaglandin E2 mediated control.", "content": "Isolated superfused field  stimulated human omental arteries and veins, preincubated with 3H (-)-noradrenaline (NA) were used to study the frequency dependence of NA secretion and of the mechanisms  for its local feedback control. 3H-NA secretion per shock was found to be basically a simple hyperbolic function of the stimulation frequency from 1 to 30 Hz, as long as secretion was restricted by prostaglandin E2 (PGE2). In the absence of restriction, or during facilitation, 3H-NA secretion per shock reached its maximum at 10 Hz and then declined at 30 Hz, indicating 'overload' in some link in the secretory mechanism. 3H-NA secretion was depressed by exogenous NA and by PGE2, and enchanced by isoprenaline, phentolamine and by blockade of PGE2 formation. Most of these effects were inversely related to the stimulation frequency. Attempts were made to study interactions between the different control mechanisms and to evaluate possible in vivo consequences of disturbance of adrenergic neuroeffector transmission by interference with the local control of the secretory mechanisms.", "contents": "Frequency-dependence of 3H-noradrenaline secretion from human vasoconstrictor nerves: modification by factors interfering with alpha-or beta-adrenoceptor or prostaglandin E2 mediated control. Isolated superfused field  stimulated human omental arteries and veins, preincubated with 3H (-)-noradrenaline (NA) were used to study the frequency dependence of NA secretion and of the mechanisms  for its local feedback control. 3H-NA secretion per shock was found to be basically a simple hyperbolic function of the stimulation frequency from 1 to 30 Hz, as long as secretion was restricted by prostaglandin E2 (PGE2). In the absence of restriction, or during facilitation, 3H-NA secretion per shock reached its maximum at 10 Hz and then declined at 30 Hz, indicating 'overload' in some link in the secretory mechanism. 3H-NA secretion was depressed by exogenous NA and by PGE2, and enchanced by isoprenaline, phentolamine and by blockade of PGE2 formation. Most of these effects were inversely related to the stimulation frequency. Attempts were made to study interactions between the different control mechanisms and to evaluate possible in vivo consequences of disturbance of adrenergic neuroeffector transmission by interference with the local control of the secretory mechanisms."}
{"id": "PMID:200069", "title": "Comparison of two muscle relaxant drugs on human sleep: diazepam and parachlorophenylgaba.", "content": "The effects of two muscle relaxant drugs of different chemical structures, parachlorophenylgaba and diazepam, were investigated in the sleep of normal young adults. Parachlorophenylgaba did not show any significant and dose-related effect. In contrast, diazepam induced clear modifications, including a decrease of stage 4 and of REM-sleep, an increase of spindles and a decrease of K potentials in stage 2, a decrease of rapid eye movements in REM-sleep, and finally a decrease of body movements. In addition, the recovery of REM-sleep upon withdrawal of the drug was much faster than the recovery of stage 4. These results add a new contribution to known differences in the pharmacological profiles of these two compounds ; for diazepam, the possible role of GABA mediated monoaminergic mechanisms is discussed.", "contents": "Comparison of two muscle relaxant drugs on human sleep: diazepam and parachlorophenylgaba. The effects of two muscle relaxant drugs of different chemical structures, parachlorophenylgaba and diazepam, were investigated in the sleep of normal young adults. Parachlorophenylgaba did not show any significant and dose-related effect. In contrast, diazepam induced clear modifications, including a decrease of stage 4 and of REM-sleep, an increase of spindles and a decrease of K potentials in stage 2, a decrease of rapid eye movements in REM-sleep, and finally a decrease of body movements. In addition, the recovery of REM-sleep upon withdrawal of the drug was much faster than the recovery of stage 4. These results add a new contribution to known differences in the pharmacological profiles of these two compounds ; for diazepam, the possible role of GABA mediated monoaminergic mechanisms is discussed."}
{"id": "PMID:200096", "title": "The characteristics of human plasma lipoprotein metabolism: influence of low caloric diet on hyperlipidemia.", "content": "We have classified hyperlipidemia into three groups according to different levels of VLDL-TG, and postulated the effect of low calorie-diets on plasma TCh are as follows: 1) Low calorie-diets are effective on VLDL-TG in every type of hyperlipidemia, except hyperlipidemia with VLDL-TG under 180 mg/100ml; 2) There was a reciprocal relation between the decreased amount of plasma TCh and the change VLDL-TG induced by the diet; 3) Catabolism of VLDL was accelerated by an increased esterification of VLDL-FC; 4) In the the group with VLDL-TG less than or equal to 180 mg/100ml, the LDC showed a high level of TCh: protein ration, and in the group with VLDL-TG greater than or equal to 260 mg/100ml, there was to be low level of TG: protein ratio in VLDL: 5) In hyperlipidemia with plasma TCh unchanged by the diet LDL-TCh increased significantly without any increase in LDL protein and LDL-TG.", "contents": "The characteristics of human plasma lipoprotein metabolism: influence of low caloric diet on hyperlipidemia. We have classified hyperlipidemia into three groups according to different levels of VLDL-TG, and postulated the effect of low calorie-diets on plasma TCh are as follows: 1) Low calorie-diets are effective on VLDL-TG in every type of hyperlipidemia, except hyperlipidemia with VLDL-TG under 180 mg/100ml; 2) There was a reciprocal relation between the decreased amount of plasma TCh and the change VLDL-TG induced by the diet; 3) Catabolism of VLDL was accelerated by an increased esterification of VLDL-FC; 4) In the the group with VLDL-TG less than or equal to 180 mg/100ml, the LDC showed a high level of TCh: protein ration, and in the group with VLDL-TG greater than or equal to 260 mg/100ml, there was to be low level of TG: protein ratio in VLDL: 5) In hyperlipidemia with plasma TCh unchanged by the diet LDL-TCh increased significantly without any increase in LDL protein and LDL-TG."}
{"id": "PMID:200102", "title": "The origin and fate of HDL.", "content": "High density lipoproteins are synthesized both in the liver and intestine. All apoproteins can be synthesized in the liver and intestine except the \"C\" apoproteins which could not be synthesized by the intestine. After injection of 125I-HDL its different apoproteins are removed from the circulation at a similar rate. Most of the HDL is removed by the liver and the degradation of the protein moiety of HDL was localized to the lysozomes of the parenchymal cells. Cholesterol feeding alters the distribution of lipoprotein fractions and results in the appearance of a new intermediate density class, in which all HDL apoproteins are present in addition to apo-B. Cholesterol feeding also results in an alteration of apoprotein composition of HDL.", "contents": "The origin and fate of HDL. High density lipoproteins are synthesized both in the liver and intestine. All apoproteins can be synthesized in the liver and intestine except the \"C\" apoproteins which could not be synthesized by the intestine. After injection of 125I-HDL its different apoproteins are removed from the circulation at a similar rate. Most of the HDL is removed by the liver and the degradation of the protein moiety of HDL was localized to the lysozomes of the parenchymal cells. Cholesterol feeding alters the distribution of lipoprotein fractions and results in the appearance of a new intermediate density class, in which all HDL apoproteins are present in addition to apo-B. Cholesterol feeding also results in an alteration of apoprotein composition of HDL."}
{"id": "PMID:200115", "title": "Regulatory function of delta6 desaturate -- key enzyme of polyunsaturated fatty acid synthesis.", "content": "The delta6 desaturation of unsaturated acyl-CoA is the first reaction involved in the normal biosynthesis of all polyunsaturated fatty acids families in animal microsomes. Due to this key position it can regulate the biosynthesis of the fatty acids of the series. The reaction is modified by competition with substrates and products, ATP, and acyl-CoA acceptors. Dietary glucose and fructose inhibit the enzyme whereas protein diets and essential fatty acid deficient diets enhance the reaction independently of hormonal effects. The enzyme is sensitive to hormones concentration. Insulin enhance the reaction but the effect is eliminated by protein synthesis inhibition. Hyperglucemic hormones as glucagon, and epinephrine depress the activity of the delta6 desaturase by reactions triggers by an increase of cAMP concentration. The lateral relation of linoleic or alpha-linolenic microsomal elongation is insensitive to insulin, glucagon, epinephrine and protein. All these effects have been proved by either in vivo experiments or cell culture using linoleic or alpha-linolenic acids as substrates.", "contents": "Regulatory function of delta6 desaturate -- key enzyme of polyunsaturated fatty acid synthesis. The delta6 desaturation of unsaturated acyl-CoA is the first reaction involved in the normal biosynthesis of all polyunsaturated fatty acids families in animal microsomes. Due to this key position it can regulate the biosynthesis of the fatty acids of the series. The reaction is modified by competition with substrates and products, ATP, and acyl-CoA acceptors. Dietary glucose and fructose inhibit the enzyme whereas protein diets and essential fatty acid deficient diets enhance the reaction independently of hormonal effects. The enzyme is sensitive to hormones concentration. Insulin enhance the reaction but the effect is eliminated by protein synthesis inhibition. Hyperglucemic hormones as glucagon, and epinephrine depress the activity of the delta6 desaturase by reactions triggers by an increase of cAMP concentration. The lateral relation of linoleic or alpha-linolenic microsomal elongation is insensitive to insulin, glucagon, epinephrine and protein. All these effects have been proved by either in vivo experiments or cell culture using linoleic or alpha-linolenic acids as substrates."}
{"id": "PMID:200116", "title": "Electron paramagnetic resonance studies of ethanol on membrane fluidity.", "content": "An optimum level of fluidity in the membrane appears to be important for some physiological functions. The present studies examined the effects of ethanol in erythrocyte and brain membrane preparations from Swiss Webster mice using electron paramagnetic resonance (EPR) techniques with a fatty acid spin label. The spectral parameter measured was the order parmeter, S, an index of membrane fluidity. Synaptosomal membranes were more fluid than myelin but less fluid than mitochondrial membranes. In low concentrations of 1 and 2 mg/ml of ethanol membrane fluidity was increased in mitochondrial, synaptosomal, and erythrocyte membranes. Dose-related increases in membrane fluidity were also observed at higher concentrations of 4, 8 and 16 mg/ml of ethanol for all of the membranes except myelin. These data indicate that non-lethal concentrations of ethanol may increase membrane fluidity in vivo.", "contents": "Electron paramagnetic resonance studies of ethanol on membrane fluidity. An optimum level of fluidity in the membrane appears to be important for some physiological functions. The present studies examined the effects of ethanol in erythrocyte and brain membrane preparations from Swiss Webster mice using electron paramagnetic resonance (EPR) techniques with a fatty acid spin label. The spectral parameter measured was the order parmeter, S, an index of membrane fluidity. Synaptosomal membranes were more fluid than myelin but less fluid than mitochondrial membranes. In low concentrations of 1 and 2 mg/ml of ethanol membrane fluidity was increased in mitochondrial, synaptosomal, and erythrocyte membranes. Dose-related increases in membrane fluidity were also observed at higher concentrations of 4, 8 and 16 mg/ml of ethanol for all of the membranes except myelin. These data indicate that non-lethal concentrations of ethanol may increase membrane fluidity in vivo."}
{"id": "PMID:200117", "title": "Regulatory factors of acetaldehyde metabolism in isolated rat liver mitochondria.", "content": "The factors affecting acetaldehyde oxidation were studied by direct measurement of redox changes of NADH and cytochrome c in isolated rat liver mitochondria which contain the natural complement of mitochondrial substrates and co-factors, etc. Thus, this system affords a quantitative model for mitochondrial acetaldehyde metabolism simulating in vivo conditions. The activity of acetaldehyde dehydrogenase, as measured by the turnover number of cytochrome c, k3, depends upon the substrate concentration in a complex way. It reaches a maximum below 0.033 mM acetaldehyde and decreases abruptly at higher acetaldehyde concentration, interpreted here to be due to substrate inhibition. When mitochondria undergo hypotonic swelling, the maximal value of k3 is lowered by a factor of 15 and the substrate inhibition largely disappears. When mitochondria are stripped of the outer membrane and are suspended in pyrophosphate buffer, similar effects are obtained. It is concluded that acetaldehyde oxidation in mitochondria is dependent upon the state of mitochondria and the substrate concentration, and that the mitochondrial metabolism of acetaldehyde cannot be accurately predicted from in vitro data of solubilized enzyme.", "contents": "Regulatory factors of acetaldehyde metabolism in isolated rat liver mitochondria. The factors affecting acetaldehyde oxidation were studied by direct measurement of redox changes of NADH and cytochrome c in isolated rat liver mitochondria which contain the natural complement of mitochondrial substrates and co-factors, etc. Thus, this system affords a quantitative model for mitochondrial acetaldehyde metabolism simulating in vivo conditions. The activity of acetaldehyde dehydrogenase, as measured by the turnover number of cytochrome c, k3, depends upon the substrate concentration in a complex way. It reaches a maximum below 0.033 mM acetaldehyde and decreases abruptly at higher acetaldehyde concentration, interpreted here to be due to substrate inhibition. When mitochondria undergo hypotonic swelling, the maximal value of k3 is lowered by a factor of 15 and the substrate inhibition largely disappears. When mitochondria are stripped of the outer membrane and are suspended in pyrophosphate buffer, similar effects are obtained. It is concluded that acetaldehyde oxidation in mitochondria is dependent upon the state of mitochondria and the substrate concentration, and that the mitochondrial metabolism of acetaldehyde cannot be accurately predicted from in vitro data of solubilized enzyme."}
{"id": "PMID:200119", "title": "Changes in receptor sensitivity of the cerebral cortex and liver during chronic ethanol ingestion and withdrawal.", "content": "The evidence was reviewed supporting the noradrenergic sub- and supersensitivity hypothesis of ethanol withdrawal pathogenesis. New data indicates that the cAMP generating system linked to noradrenergic receptor sensitivity is in a steady state in the brain during ethanol withdrawal since the cAMP levels were not different from controls in vivo. Propranolol blocking experiments indicated the beta-adrenergic receptor is a necessary link in the increased cAMP response induced by ethanol withdrawal. The changes in sensitivity observed in the ethanol withdrawn rats were reproduced by acute and chronic reserpinization.", "contents": "Changes in receptor sensitivity of the cerebral cortex and liver during chronic ethanol ingestion and withdrawal. The evidence was reviewed supporting the noradrenergic sub- and supersensitivity hypothesis of ethanol withdrawal pathogenesis. New data indicates that the cAMP generating system linked to noradrenergic receptor sensitivity is in a steady state in the brain during ethanol withdrawal since the cAMP levels were not different from controls in vivo. Propranolol blocking experiments indicated the beta-adrenergic receptor is a necessary link in the increased cAMP response induced by ethanol withdrawal. The changes in sensitivity observed in the ethanol withdrawn rats were reproduced by acute and chronic reserpinization."}
{"id": "PMID:200120", "title": "The metabolism of biogenic amines in experimental animals and in human subjects during acute and chronic administration of ethanol.", "content": "Ethanol has been shown to induce a shift in catecholamine metabolism peripherally from normally oxidative pathways to reductive pathways. The mechanisms of this effect may result from competitive inhibition of aldehyde dehydrogenase by acetaldehyde. The shift in metabolism cannot be found in brain and alterations in catecholamine function may reflect changes in the turnover of these amines.", "contents": "The metabolism of biogenic amines in experimental animals and in human subjects during acute and chronic administration of ethanol. Ethanol has been shown to induce a shift in catecholamine metabolism peripherally from normally oxidative pathways to reductive pathways. The mechanisms of this effect may result from competitive inhibition of aldehyde dehydrogenase by acetaldehyde. The shift in metabolism cannot be found in brain and alterations in catecholamine function may reflect changes in the turnover of these amines."}
{"id": "PMID:200121", "title": "Alcohol, sleep and cerebrospinal fluid changes in alcoholics: cyclic AMP and biogenic amine metabolites in CSF.", "content": "Relative to baseline, one day of alcohol ingestion by chronic alcoholics demonstrated significant increases in SWS, decreases in REM sleep and decreases in CSF levels of cyclic AMP and 5-HIAA.", "contents": "Alcohol, sleep and cerebrospinal fluid changes in alcoholics: cyclic AMP and biogenic amine metabolites in CSF. Relative to baseline, one day of alcohol ingestion by chronic alcoholics demonstrated significant increases in SWS, decreases in REM sleep and decreases in CSF levels of cyclic AMP and 5-HIAA."}
{"id": "PMID:200133", "title": "Asymptomatic gonorrhea.", "content": "Asymptomatic gonorrhea is significantly common in both males and females. A patient with one sexually transmitted disease (STD) is more likely to have an asymptomatic gonorrheal infection. A physician seeing a patient with an STD should obtain a culture for Neisseria gonorrhoeae to check for a possible asymptomatic infection. Routine culturing of this sexually active population will help to control the increasing incidence of gonorrhea. Appropriate treatment should be initiated by the physician who makes the diagnosis of gonorrhea.", "contents": "Asymptomatic gonorrhea. Asymptomatic gonorrhea is significantly common in both males and females. A patient with one sexually transmitted disease (STD) is more likely to have an asymptomatic gonorrheal infection. A physician seeing a patient with an STD should obtain a culture for Neisseria gonorrhoeae to check for a possible asymptomatic infection. Routine culturing of this sexually active population will help to control the increasing incidence of gonorrhea. Appropriate treatment should be initiated by the physician who makes the diagnosis of gonorrhea."}
{"id": "PMID:200137", "title": "LDH isoenzyme electrophoretic pattern differences between colloid and other adenocarcinomas of the colon.", "content": "LDH isoenzyme electrophoretic patterns have been studied in 27 adenocarcinomas of the colon. The different content of M monomer in poorly differentiated tumors is statistically significant (P less than 0.001) when compared to well-differentiated tumors of the colon. Such a difference has not been found for two Broders groups of well-differentiated tumors. A commentary is made on the possibilities of histochemistry and cytochemistry providing better classification of these tumors.", "contents": "LDH isoenzyme electrophoretic pattern differences between colloid and other adenocarcinomas of the colon. LDH isoenzyme electrophoretic patterns have been studied in 27 adenocarcinomas of the colon. The different content of M monomer in poorly differentiated tumors is statistically significant (P less than 0.001) when compared to well-differentiated tumors of the colon. Such a difference has not been found for two Broders groups of well-differentiated tumors. A commentary is made on the possibilities of histochemistry and cytochemistry providing better classification of these tumors."}
{"id": "PMID:200138", "title": "Effects of blood glucose levels on aspirin-induced gastric mucosal damage.", "content": "In female rats aspirin-induced gastrin mucosal damage was increased and glycoprotein synthesis decreased by fasting and by insulin administration. Glucose added to the drinking water during the fasting period reduced mucosal damage and increased glycoprotein synthesis to control levels. Alloxan diabetes did not affect mucosal damage or glycoprotein synthesis. Alloxan diabetes plus insulin restored blood glucose levels to normal, and susceptibility to aspirin damage and glycoprotein synthesis were also normal. Alloxan diabetes plus fasting restored blood glucose levels to normal but increased aspirin-induced mucosal damage and reduced glycoprotein synthesis. In vitro incubation of gastric mucosal homogenates showed that diburyryl cyclic AMP and theophylline inhibited glycoprotein synthesis but dibutyryl cyclic GMP had no significant effects. The importance of an adequate supply of glucose to the gastric mucosa and the effects of cyclic nucleotides on glycoprotein synthesis are discussed.", "contents": "Effects of blood glucose levels on aspirin-induced gastric mucosal damage. In female rats aspirin-induced gastrin mucosal damage was increased and glycoprotein synthesis decreased by fasting and by insulin administration. Glucose added to the drinking water during the fasting period reduced mucosal damage and increased glycoprotein synthesis to control levels. Alloxan diabetes did not affect mucosal damage or glycoprotein synthesis. Alloxan diabetes plus insulin restored blood glucose levels to normal, and susceptibility to aspirin damage and glycoprotein synthesis were also normal. Alloxan diabetes plus fasting restored blood glucose levels to normal but increased aspirin-induced mucosal damage and reduced glycoprotein synthesis. In vitro incubation of gastric mucosal homogenates showed that diburyryl cyclic AMP and theophylline inhibited glycoprotein synthesis but dibutyryl cyclic GMP had no significant effects. The importance of an adequate supply of glucose to the gastric mucosa and the effects of cyclic nucleotides on glycoprotein synthesis are discussed."}
{"id": "PMID:200140", "title": "Epidemic keratoconjunctivitis at a Vietnamese refugee camp in Florida.", "content": "During the summer of 1975 an ongoing outbreak of conjunctivitis occurred among Vietnamese refugees temporarily housed at a U.S. mainland camp. Twenty-two per cent of surveyed refugees gave a history of the disease and 10% were documented as having clinical conjunctivitis at the time of the survey. Fifty-six per cent of documented cases were in children less than 10 years of age. The attack rate among American camp personnel was 4%. Comprehensive microbiologic analysis revealed multiple potential pathogens in most cases, but the recovery of adenovirus 8 (AV8) in 81% of cases cultured within two weeks of onset implicated AV8 as the principal cause of the epidemic.", "contents": "Epidemic keratoconjunctivitis at a Vietnamese refugee camp in Florida. During the summer of 1975 an ongoing outbreak of conjunctivitis occurred among Vietnamese refugees temporarily housed at a U.S. mainland camp. Twenty-two per cent of surveyed refugees gave a history of the disease and 10% were documented as having clinical conjunctivitis at the time of the survey. Fifty-six per cent of documented cases were in children less than 10 years of age. The attack rate among American camp personnel was 4%. Comprehensive microbiologic analysis revealed multiple potential pathogens in most cases, but the recovery of adenovirus 8 (AV8) in 81% of cases cultured within two weeks of onset implicated AV8 as the principal cause of the epidemic."}
{"id": "PMID:200142", "title": "Effect of maternal isoxsuprine on fetal rabbit lung biochemical maturation.", "content": "Isoxsuprine was given intramuscularly for 24 hours to pregnant rabbits at 26 to 27 days' gestation. There was no effect on fetal weight within one day of the last injection. Fetuses of isoxsuprine-treated mothers had higher lung lecithin (6.67 micron per gram +/- 2.81) and higher tracheal wash lecithin/sphingomyelin (L/S) ratios (5.85 +/- 4.5) than did untreated fetuses--lung lecithin (5.35 micron per gram 1.23) and tracheal wash L/S (4.08 +/- 2.3). In contrast, phosphorylcholine glyceride transferase activity of the fetal lung was less in isoxsuprine-treated fetal lung tissue.", "contents": "Effect of maternal isoxsuprine on fetal rabbit lung biochemical maturation. Isoxsuprine was given intramuscularly for 24 hours to pregnant rabbits at 26 to 27 days' gestation. There was no effect on fetal weight within one day of the last injection. Fetuses of isoxsuprine-treated mothers had higher lung lecithin (6.67 micron per gram +/- 2.81) and higher tracheal wash lecithin/sphingomyelin (L/S) ratios (5.85 +/- 4.5) than did untreated fetuses--lung lecithin (5.35 micron per gram 1.23) and tracheal wash L/S (4.08 +/- 2.3). In contrast, phosphorylcholine glyceride transferase activity of the fetal lung was less in isoxsuprine-treated fetal lung tissue."}
{"id": "PMID:200143", "title": "Differences in growth of transplants of liver, liver hyperplastic nodules, and hepatocellular carcinomas in the mammary fat pad.", "content": "Transplantation of fragments of normal rat liver autologously and isologously into the inguinal mammary fat pad permitted survival for up to 75% of grafts for 38 weeks, the longest interval studied. Similarly transplanted hepatocarcinomas grew rapidly and progressively in this site. Neither autologous or isologous transplants of liver hyperplastic nodules displayed obvious growth, although like normal liver, they also persisted for up to 38 weeks. Some persisting hyperplastic cells retained certain characteristic features, but others appeared to revert to a normal morphology. Thus, there is a stage in which hyperplastic cells do not possess the progressive growth ability of neoplastic cells and appear to be capable of reversion to a normal phenotype.", "contents": "Differences in growth of transplants of liver, liver hyperplastic nodules, and hepatocellular carcinomas in the mammary fat pad. Transplantation of fragments of normal rat liver autologously and isologously into the inguinal mammary fat pad permitted survival for up to 75% of grafts for 38 weeks, the longest interval studied. Similarly transplanted hepatocarcinomas grew rapidly and progressively in this site. Neither autologous or isologous transplants of liver hyperplastic nodules displayed obvious growth, although like normal liver, they also persisted for up to 38 weeks. Some persisting hyperplastic cells retained certain characteristic features, but others appeared to revert to a normal morphology. Thus, there is a stage in which hyperplastic cells do not possess the progressive growth ability of neoplastic cells and appear to be capable of reversion to a normal phenotype."}
{"id": "PMID:200145", "title": "Effect of oxygen tension on cellular energetics.", "content": "Simultaneous measurements of the mitochondrial [NAD+]/[NADH], the cytoplasmic [ATP]/[ADP] x [Pi], and the respiratory rate were carried out in suspensions of cultured kidney cells in a range of defined oxygen tensions. The results show that as the extracellular oxygen concentration falls there is a decrease in the respiratory rate, which is accompanied by a decrease in the [ATP]/[ADP] and a progressive reduction of cytochrome c. Even at low O2 tensions the mitochondrial respiratory chain between the NAD couple and cytochrome c remains at near equilibrium with the ATP synthesizing reactions. It is concluded that limited oxygen supply affects cellular metabolism at much higher concentrations than the P50 value for the oxygen dependence of respiration, but the respiratory rate remains relatively unchanged due to compensatory changes in the [ATP]/[ADP] X [Pi] and progressive reduction of cytochrome c. These metabolic changes may form a basis for the phenomenon of tissue oxygen sensing at near physiological oxygen tensions.", "contents": "Effect of oxygen tension on cellular energetics. Simultaneous measurements of the mitochondrial [NAD+]/[NADH], the cytoplasmic [ATP]/[ADP] x [Pi], and the respiratory rate were carried out in suspensions of cultured kidney cells in a range of defined oxygen tensions. The results show that as the extracellular oxygen concentration falls there is a decrease in the respiratory rate, which is accompanied by a decrease in the [ATP]/[ADP] and a progressive reduction of cytochrome c. Even at low O2 tensions the mitochondrial respiratory chain between the NAD couple and cytochrome c remains at near equilibrium with the ATP synthesizing reactions. It is concluded that limited oxygen supply affects cellular metabolism at much higher concentrations than the P50 value for the oxygen dependence of respiration, but the respiratory rate remains relatively unchanged due to compensatory changes in the [ATP]/[ADP] X [Pi] and progressive reduction of cytochrome c. These metabolic changes may form a basis for the phenomenon of tissue oxygen sensing at near physiological oxygen tensions."}
{"id": "PMID:200144", "title": "Considerations on the preneoplastic lesions of the mammary gland.", "content": "The general characteristics of the preneoplastic lesions of the human mammary gland, as they are known through histologic description, are outlined, and data obtained from the experimental analysis of mammary gland preneoplasia in five areas of endeavor are discussed. Results obtained with transplantation procedures and aimed at defining the growth potential of hyperplastic outgrowths are reported. Information derived from the study of events able to induce benign hyperplastic outgrowths or their malignant transformation in the murine mammary gland is summarized. Attempts to predict neoplastic transformation in morphologically hyperplastic epithelium of human and rodent glands are discussed. The present status of efforts toward the prophylaxis of preneoplastic lesions of the mammary gland is described. Considerations of the relationship between preneoplasia and tumor dormancy conclude the presentation.", "contents": "Considerations on the preneoplastic lesions of the mammary gland. The general characteristics of the preneoplastic lesions of the human mammary gland, as they are known through histologic description, are outlined, and data obtained from the experimental analysis of mammary gland preneoplasia in five areas of endeavor are discussed. Results obtained with transplantation procedures and aimed at defining the growth potential of hyperplastic outgrowths are reported. Information derived from the study of events able to induce benign hyperplastic outgrowths or their malignant transformation in the murine mammary gland is summarized. Attempts to predict neoplastic transformation in morphologically hyperplastic epithelium of human and rodent glands are discussed. The present status of efforts toward the prophylaxis of preneoplastic lesions of the mammary gland is described. Considerations of the relationship between preneoplasia and tumor dormancy conclude the presentation."}
{"id": "PMID:200146", "title": "Estimates of quantal-release and binomial statistical-release parameters at rat neuromuscular junction.", "content": "Quantal-release and binomial statistical-release parameters were examined in the isolated rat diaphragm phrenic nerve preparation. The muscle resting potentials were reduced by cutting the muscle fibers to prevent muscle action potentials and contractions. The cutting technique was modified to allow persistent observation of miniature end-plate potentials (MEPPs) and end-plate potentials (EPPs) with intracellular recording techniques. Direct estimates of quantal release were examined and compared with predicted binomial and Poisson distributions. The results indicate that release is binomial when the nerve is stimulated with low- or high-frequency stimuli. The indirect method of estimating quantal release (variance method), which assumes release is described by a Poisson distribution, seriously overestimates quantal release. The binomial analysis indicates that the statistical store is small (less than 90 quanta) and that most of these quanta are released with each nerve impulse.", "contents": "Estimates of quantal-release and binomial statistical-release parameters at rat neuromuscular junction. Quantal-release and binomial statistical-release parameters were examined in the isolated rat diaphragm phrenic nerve preparation. The muscle resting potentials were reduced by cutting the muscle fibers to prevent muscle action potentials and contractions. The cutting technique was modified to allow persistent observation of miniature end-plate potentials (MEPPs) and end-plate potentials (EPPs) with intracellular recording techniques. Direct estimates of quantal release were examined and compared with predicted binomial and Poisson distributions. The results indicate that release is binomial when the nerve is stimulated with low- or high-frequency stimuli. The indirect method of estimating quantal release (variance method), which assumes release is described by a Poisson distribution, seriously overestimates quantal release. The binomial analysis indicates that the statistical store is small (less than 90 quanta) and that most of these quanta are released with each nerve impulse."}
{"id": "PMID:200147", "title": "Rat adrenal cell sensitivity to angiotensin II, alpha-1-24-ACTH, and potassium: a comparative study.", "content": "Rat adrenal glomerulosa and fasciculata-reticularis cell sensitivity to comparable molar doses of angiotensin II (AII) (2.4 X 10(-12) to 2.4 X 10(-4) M) and ACTH (alpha-1-24-adrenocorticotropin) (3.5 X 10(-13) to 3.5 X 10(-8) M) as well as small increments in potassium (K+) (3.7 to 13 meq/liter) was investigated. Glomerulose cells responded to physiological levels of AII (2.4 X 10(-10) M) and alpha-1-24-ACTH (3.5 X 10(-12) M), whereas an increment of as little 0.3 meq/liter in medium K+ also significantly increased aldosterone production. Of the three stimuli, alpha-1-24-ACTH caused the greatest aldosterone rise (11 times control). Fasciculata-reticularis cells responded only to alpha-1-24-ACTH. Whereas the threshold sensitivity was no lower than with glomerulosa cells, the maximum response was significantly greater (63 times control). These findings are consistent with findings documented in vivo in man, suggesting that the control of aldosterone secretion is similar in these two species.", "contents": "Rat adrenal cell sensitivity to angiotensin II, alpha-1-24-ACTH, and potassium: a comparative study. Rat adrenal glomerulosa and fasciculata-reticularis cell sensitivity to comparable molar doses of angiotensin II (AII) (2.4 X 10(-12) to 2.4 X 10(-4) M) and ACTH (alpha-1-24-adrenocorticotropin) (3.5 X 10(-13) to 3.5 X 10(-8) M) as well as small increments in potassium (K+) (3.7 to 13 meq/liter) was investigated. Glomerulose cells responded to physiological levels of AII (2.4 X 10(-10) M) and alpha-1-24-ACTH (3.5 X 10(-12) M), whereas an increment of as little 0.3 meq/liter in medium K+ also significantly increased aldosterone production. Of the three stimuli, alpha-1-24-ACTH caused the greatest aldosterone rise (11 times control). Fasciculata-reticularis cells responded only to alpha-1-24-ACTH. Whereas the threshold sensitivity was no lower than with glomerulosa cells, the maximum response was significantly greater (63 times control). These findings are consistent with findings documented in vivo in man, suggesting that the control of aldosterone secretion is similar in these two species."}
{"id": "PMID:200148", "title": "Cardiopulmonary sympathetic afferent influences on renal nerve activity.", "content": "Cardiopulmonary sympathetic afferent nerves may affect renal control of intravascular volume by influencing renal sympathetic nerve activity. This influence was evaluated in alpha-chloralose anesthetized, vagotomized, sino-aortic denervated cats. When the afferent nerves were activated with a single electrical stimulus, the renal nerve responded with an excitatory burst of activity followed by a long period of inhibition. This response had characteristics of a supraspinal reflex. Repetitive stimulation of the sympathetic afferent nerve either inhibited or excited renal nerves and increased or decreased systemic blood pressure. The direction of these changes depended on stimulus parameters. No obligatory correlation in the direction of change of nerve activity and blood pressure was observed. Activation of cardiopulmonary sympathetic afferent nerves by intravascular volume expansion inhibited renal nerve discharge. Inhibition was elminated by sectioning the sympathetic afferent nerves. Volume expansion had no effect on lumbar sympathetic discharge monitored simultaneously with renal nerve activity. This observation suggests specificity of reflex influences of these afferent nerves on the kidney. In conclusion, cardiopulmonary sympathetic afferent nerves can reflexly alter renal nerve activity, and therefore may affect renal control of intravascular volume.", "contents": "Cardiopulmonary sympathetic afferent influences on renal nerve activity. Cardiopulmonary sympathetic afferent nerves may affect renal control of intravascular volume by influencing renal sympathetic nerve activity. This influence was evaluated in alpha-chloralose anesthetized, vagotomized, sino-aortic denervated cats. When the afferent nerves were activated with a single electrical stimulus, the renal nerve responded with an excitatory burst of activity followed by a long period of inhibition. This response had characteristics of a supraspinal reflex. Repetitive stimulation of the sympathetic afferent nerve either inhibited or excited renal nerves and increased or decreased systemic blood pressure. The direction of these changes depended on stimulus parameters. No obligatory correlation in the direction of change of nerve activity and blood pressure was observed. Activation of cardiopulmonary sympathetic afferent nerves by intravascular volume expansion inhibited renal nerve discharge. Inhibition was elminated by sectioning the sympathetic afferent nerves. Volume expansion had no effect on lumbar sympathetic discharge monitored simultaneously with renal nerve activity. This observation suggests specificity of reflex influences of these afferent nerves on the kidney. In conclusion, cardiopulmonary sympathetic afferent nerves can reflexly alter renal nerve activity, and therefore may affect renal control of intravascular volume."}
{"id": "PMID:200149", "title": "Sleep and hibernation in ground squirrels (Citellus spp): electrophysiological observations.", "content": "Electroencephalogram (EEG), electrooculogram, electromyogram, and electrocardiogram were recorded from ground squirrels (Citellus beldingi and C. lateralis) during the summer and also during the hibernation season. Summer recordings revealed that the animals spent an average of 66% of the 24-h period asleep (49% of the 12-h light period and 84% of the 12-h dark period); 19% of the total sleep time (TST) consisted of rapid-eye-movement (REM) sleep, and 81% of TST consisted of slow-wave sleep (SWS). Recordings obtained during the hibernation season showed that hibernation was entered through sleep, but the distribution of sleep states was different than in euthermic sleep. During the early entrance when brain temperature (Tbr) was between 35 and 25 degrees C, the animals were asleep 88% of the time, but only 10% of the TST was spent in REM sleep. The EEG amplitude declined with decreased Tbr so that classical sleep stages could not be identified below a Tbr of 25 degrees C. The frequency of the EEG increased as Tbr decreased; but activity in the 0-4 cycles/s band occupied the majority of the record even at a Tbr of 10 degrees C. Below a Tbr of 10 degrees C the EEG was isoelectric except for intermittent bursts of spindles. It was concluded from these and other results that the entrance into hibernation represents an extension of the thermoregulatory adjustments that occur during SWS.", "contents": "Sleep and hibernation in ground squirrels (Citellus spp): electrophysiological observations. Electroencephalogram (EEG), electrooculogram, electromyogram, and electrocardiogram were recorded from ground squirrels (Citellus beldingi and C. lateralis) during the summer and also during the hibernation season. Summer recordings revealed that the animals spent an average of 66% of the 24-h period asleep (49% of the 12-h light period and 84% of the 12-h dark period); 19% of the total sleep time (TST) consisted of rapid-eye-movement (REM) sleep, and 81% of TST consisted of slow-wave sleep (SWS). Recordings obtained during the hibernation season showed that hibernation was entered through sleep, but the distribution of sleep states was different than in euthermic sleep. During the early entrance when brain temperature (Tbr) was between 35 and 25 degrees C, the animals were asleep 88% of the time, but only 10% of the TST was spent in REM sleep. The EEG amplitude declined with decreased Tbr so that classical sleep stages could not be identified below a Tbr of 25 degrees C. The frequency of the EEG increased as Tbr decreased; but activity in the 0-4 cycles/s band occupied the majority of the record even at a Tbr of 10 degrees C. Below a Tbr of 10 degrees C the EEG was isoelectric except for intermittent bursts of spindles. It was concluded from these and other results that the entrance into hibernation represents an extension of the thermoregulatory adjustments that occur during SWS."}
{"id": "PMID:200150", "title": "Paget's disease of the vulva. A histogenetic study of five cases including ultrastructural observations and review of the literature.", "content": "Five cases of extramammary Paget's disease of the vulva were studied by histologic, ultrastructural, and immunologic methods. In one of these cases, the associated invasive adnexal carcinoma was studied in a similar fashion. In all five cases, carcinoma-in situ of the sweat glands was observed. In two cases, the glands were identified as aporcrine. In the other three it could not be determined whether they were apocrine or eccrine. In one case tumor cells were seen extending from a focus of underlying carcinoma-in-situ of sweat glands through the excretory duct into the surface epithelium. The ultrastructural findings indicated that the Paget's cells as well as the cells of the invasive carcinoma were adenocarcinoma cells, but the findings were not conclusive as to whether the cells were apocrine or eccrine. There was no evidence of origin of the Paget's cells from keratinocytes. We believe that the bulk of evidence favors an extraepidermal origin for extramammary Paget's disease. The tumor is most commonly derived from the secretory portion of sweat glands, probably either of apocrine or eccrine types, or the dermal or poral portion of the sweat duct. Some cases of Paget's disease are derived from other types of glands.", "contents": "Paget's disease of the vulva. A histogenetic study of five cases including ultrastructural observations and review of the literature. Five cases of extramammary Paget's disease of the vulva were studied by histologic, ultrastructural, and immunologic methods. In one of these cases, the associated invasive adnexal carcinoma was studied in a similar fashion. In all five cases, carcinoma-in situ of the sweat glands was observed. In two cases, the glands were identified as aporcrine. In the other three it could not be determined whether they were apocrine or eccrine. In one case tumor cells were seen extending from a focus of underlying carcinoma-in-situ of sweat glands through the excretory duct into the surface epithelium. The ultrastructural findings indicated that the Paget's cells as well as the cells of the invasive carcinoma were adenocarcinoma cells, but the findings were not conclusive as to whether the cells were apocrine or eccrine. There was no evidence of origin of the Paget's cells from keratinocytes. We believe that the bulk of evidence favors an extraepidermal origin for extramammary Paget's disease. The tumor is most commonly derived from the secretory portion of sweat glands, probably either of apocrine or eccrine types, or the dermal or poral portion of the sweat duct. Some cases of Paget's disease are derived from other types of glands."}
{"id": "PMID:200151", "title": "Complete devascularization of hepatic lobe with nonresectable hepatoma.", "content": "Complete dearterialization of the entire liver was carried out in three patients with nonresectable liver cell carcinoma in whom the right or left portal vein had already obstructed due to tumor thrombosis or invasion. Although remittent fever ensued for two to three weeks postoperatively in all patients, hepatic infaction never occurred in the devascularized hepatic lobes. The effect of the treatment on tumorous lesions appeared satisfactory. The results indicated that the tumor-bearing liver can tolerate nearly complete deprivation of hepatic arterial and portal blood in at least one lobe of the liver if it is not simultaneous.", "contents": "Complete devascularization of hepatic lobe with nonresectable hepatoma. Complete dearterialization of the entire liver was carried out in three patients with nonresectable liver cell carcinoma in whom the right or left portal vein had already obstructed due to tumor thrombosis or invasion. Although remittent fever ensued for two to three weeks postoperatively in all patients, hepatic infaction never occurred in the devascularized hepatic lobes. The effect of the treatment on tumorous lesions appeared satisfactory. The results indicated that the tumor-bearing liver can tolerate nearly complete deprivation of hepatic arterial and portal blood in at least one lobe of the liver if it is not simultaneous."}
{"id": "PMID:200155", "title": "Response of plasma corticosteroids and circulating leukocytes in cattle following intravenous injection of different doses of adrenocorticotropin.", "content": "The relationships among exogenous adrenocorticotropin (ACTH), plasma corticosteroids, and circulating leukocytes were studied in 7 lactating cows. Blood samples were obtained from jugular cannulas at -2, -1, and 0 hours before ACTH was injected (base line) and 0.25, 0.50, 1, 2, 3, 6, and 24 hours after injection. Plasma corticosteroids were increased progressively by injecting doses of ACTH between 1 and 200 IU. Plasma corticosteroids reached peak concentrations between 15 and 30 minutes and returned to base line within 1 to 3 hours after 1, 5, and 10 IU doses of ACTH were injected, but required as long as 6 hours after injection of 100 and 200 IU. Base line counts of circulating leukocytes averaged 7.3 X 10(3) cells/mm3 and remained unchanged after injecting 0 and 1 IU of ACTH (P less than 0.05). Significant dose-dependent increases in circulating leukocytes were detected within 2 hours after administering 5, 10, and 100 IU of ACTH. Responses to 100 and 200 IU were similar. The average concentration of leukocytes increased up to 6 hours after ACTH administration and returned to base line values within 12 to 24 hours in cows injected with 5 and 10 IU, but not until 48 hours in cows injected with 100 and 200 IU of ACTH. In contrast to the delayed and sustained responses observed for leukocytes, corticosteroid responses were rapid and transient. Moreover, the administration of 200 IU of ACTH was considered to increase circulating corticosteroids and leukocytes beyond that found in dairy cattle exposed to stress associated with overmilking, acute coliform mastitis, or parturition.", "contents": "Response of plasma corticosteroids and circulating leukocytes in cattle following intravenous injection of different doses of adrenocorticotropin. The relationships among exogenous adrenocorticotropin (ACTH), plasma corticosteroids, and circulating leukocytes were studied in 7 lactating cows. Blood samples were obtained from jugular cannulas at -2, -1, and 0 hours before ACTH was injected (base line) and 0.25, 0.50, 1, 2, 3, 6, and 24 hours after injection. Plasma corticosteroids were increased progressively by injecting doses of ACTH between 1 and 200 IU. Plasma corticosteroids reached peak concentrations between 15 and 30 minutes and returned to base line within 1 to 3 hours after 1, 5, and 10 IU doses of ACTH were injected, but required as long as 6 hours after injection of 100 and 200 IU. Base line counts of circulating leukocytes averaged 7.3 X 10(3) cells/mm3 and remained unchanged after injecting 0 and 1 IU of ACTH (P less than 0.05). Significant dose-dependent increases in circulating leukocytes were detected within 2 hours after administering 5, 10, and 100 IU of ACTH. Responses to 100 and 200 IU were similar. The average concentration of leukocytes increased up to 6 hours after ACTH administration and returned to base line values within 12 to 24 hours in cows injected with 5 and 10 IU, but not until 48 hours in cows injected with 100 and 200 IU of ACTH. In contrast to the delayed and sustained responses observed for leukocytes, corticosteroid responses were rapid and transient. Moreover, the administration of 200 IU of ACTH was considered to increase circulating corticosteroids and leukocytes beyond that found in dairy cattle exposed to stress associated with overmilking, acute coliform mastitis, or parturition."}
{"id": "PMID:200156", "title": "Detection of turkey coronaviral enteritis (bluecomb) in field epiornithics, using the direct and indirect fluorescent antibody tests.", "content": "In Minnesota, efforts have been made over the past 10 years to eliminate turkey coronaviral enteritis (TCE, bluecomb) by controlled depopulation and decontamination with a rest period before restocking. In 1973, clinical observations indicated that bluecomb was restricted to one limited area in Minnesota. Five epiornithics occurred during late 1973 and 1974, involving 5 different farms in this limited geographic area. During 1975, 3 epiornithics of TCE were investigated, involving 185,000 turkeys in 17 flocks, of which approximately 17,000 died. Naturally infected turkeys representing 7 operations between 1973 and 1976 were examined by both the direct fluorescent antibody test and indirect fluorescent antibody test (IFAT). The direct fluorescent antibody test detected coronaviral antigen in intestinal tissues during the acute phase of the disease, and the IFAT was highly useful in detecting TCE serum antibodies of turkey flocks that had recovered and were potential carriers. Therefore, an IFAT surveillance program was instituted for replacement flocks on farms where clinical epiornithics of TCE had occurred in 1974 through 1976. Operation 5 involved TCE epiornithics over a 2-year period and illustrate the importance of complete depopulation with an intensive decontamination program.", "contents": "Detection of turkey coronaviral enteritis (bluecomb) in field epiornithics, using the direct and indirect fluorescent antibody tests. In Minnesota, efforts have been made over the past 10 years to eliminate turkey coronaviral enteritis (TCE, bluecomb) by controlled depopulation and decontamination with a rest period before restocking. In 1973, clinical observations indicated that bluecomb was restricted to one limited area in Minnesota. Five epiornithics occurred during late 1973 and 1974, involving 5 different farms in this limited geographic area. During 1975, 3 epiornithics of TCE were investigated, involving 185,000 turkeys in 17 flocks, of which approximately 17,000 died. Naturally infected turkeys representing 7 operations between 1973 and 1976 were examined by both the direct fluorescent antibody test and indirect fluorescent antibody test (IFAT). The direct fluorescent antibody test detected coronaviral antigen in intestinal tissues during the acute phase of the disease, and the IFAT was highly useful in detecting TCE serum antibodies of turkey flocks that had recovered and were potential carriers. Therefore, an IFAT surveillance program was instituted for replacement flocks on farms where clinical epiornithics of TCE had occurred in 1974 through 1976. Operation 5 involved TCE epiornithics over a 2-year period and illustrate the importance of complete depopulation with an intensive decontamination program."}
{"id": "PMID:200157", "title": "The prognosis of lung cancer originating as a round lesion. Data from the Philadelphia pulmonary neoplasm research project.", "content": "A population of 6,027 men 45 or more years of age was screened every 6 months for 10 years with chest photofluorograms and questionnaires regarding symptoms. Although volunteers, they were similar to older men in the general population with respect to age, race, and smoking habits. Of 121 men who developed lung cancer after the beginning of observation, 48 had neoplasms appearing as round lesions at the time of radiographic detection. Only 8 per cent of the 48 men survived 5 years or more, a rate identical to that of men in whom cancer first appeared in some other form. There was an inverse relationship between initial size of the cancer and survival. Two thirds of the tumors were squamous cell carcinomas. Comparison with the literature suggests that selection accounts for the favorable prognosis of round lung cancers in hospital-based series.", "contents": "The prognosis of lung cancer originating as a round lesion. Data from the Philadelphia pulmonary neoplasm research project. A population of 6,027 men 45 or more years of age was screened every 6 months for 10 years with chest photofluorograms and questionnaires regarding symptoms. Although volunteers, they were similar to older men in the general population with respect to age, race, and smoking habits. Of 121 men who developed lung cancer after the beginning of observation, 48 had neoplasms appearing as round lesions at the time of radiographic detection. Only 8 per cent of the 48 men survived 5 years or more, a rate identical to that of men in whom cancer first appeared in some other form. There was an inverse relationship between initial size of the cancer and survival. Two thirds of the tumors were squamous cell carcinomas. Comparison with the literature suggests that selection accounts for the favorable prognosis of round lung cancers in hospital-based series."}
{"id": "PMID:200160", "title": "Type III hyperlipoproteinemia: diagnosis in whole plasma by apolipoprotein-E immunoassay.", "content": "Because the cholesterol-rich very low density (VLD) lipoproteins of subjects with type III hyperlipoproteinemia are distinctively enriched in apolipoprotein E, a radial immunodiffusion assay for apolipoprotein E in whole plasma was developed. Its diagnostic usefulness was tested in randomly selected (n = 174) and hyperlipidemic (n = 61) subsets of an adult employee population and a hyperlipidemia clinic referral group (n = 63), which included 18 patients with well-documented type III hyperlipoproteinemia. Apolipoprotein-E levels were normally distributed among the random population subset, were equal between the two sexes, and increased little with age. The mean and 99th percentile values were 24.6 and 40.1 mg/dl, respectively. All subjects with type III patterns as assigned by standard criteria from both population (n = 4) and referral sources exceeded this 99th percentile (chi +/- SD = 54.7 +/- 9.7 mg/dl). Hence a plasma apolipoprotein-E concentration exceeding 40 mg/dl appears diagnostic of type III hyperlipoproteinemia, representing the first application of an apolipoprotein immunoassay to improved diagnosis of the hyperlipoproteinemias.", "contents": "Type III hyperlipoproteinemia: diagnosis in whole plasma by apolipoprotein-E immunoassay. Because the cholesterol-rich very low density (VLD) lipoproteins of subjects with type III hyperlipoproteinemia are distinctively enriched in apolipoprotein E, a radial immunodiffusion assay for apolipoprotein E in whole plasma was developed. Its diagnostic usefulness was tested in randomly selected (n = 174) and hyperlipidemic (n = 61) subsets of an adult employee population and a hyperlipidemia clinic referral group (n = 63), which included 18 patients with well-documented type III hyperlipoproteinemia. Apolipoprotein-E levels were normally distributed among the random population subset, were equal between the two sexes, and increased little with age. The mean and 99th percentile values were 24.6 and 40.1 mg/dl, respectively. All subjects with type III patterns as assigned by standard criteria from both population (n = 4) and referral sources exceeded this 99th percentile (chi +/- SD = 54.7 +/- 9.7 mg/dl). Hence a plasma apolipoprotein-E concentration exceeding 40 mg/dl appears diagnostic of type III hyperlipoproteinemia, representing the first application of an apolipoprotein immunoassay to improved diagnosis of the hyperlipoproteinemias."}
{"id": "PMID:200161", "title": "Type III hyperlipoproteinemia: paradoxical hypolipidemic response to estrogen.", "content": "Exogenous estrogens (ethinyl estradiol, 1 microgram/kg body weight per day), which stimulate triglyceride production in normal women and those with endogenous hypertriglyceridemia, were found to exert a paradoxical, hypolipidemic effect in six subjects (five women, one man) with type III hyperlipoproteinemia on diets both of normal and of fat-free, high-carbohydrate composition. Moreover, very low-density (VLD) lipoprotein lipid and apolipoprotein composition and electrophoretic mobility became normal during estrogen administration in these subjects. Levels of normal VLD lipoproteins remained mildly to moderately elevated in a type IV lipoprotein pattern. Estrogen withdrawal promptly restored the type III pattern with its abnormal enrichment of VLD lipoproteins with apolipoprotein E (the arginine-rich peptide). These findings suggest that estrogens facilitate the assimilation of chylomicron and VLD lipoprotein remnants, a defect that appears likely to represent the metabolic abnormality underlying type III hyperlipoproteinemia.", "contents": "Type III hyperlipoproteinemia: paradoxical hypolipidemic response to estrogen. Exogenous estrogens (ethinyl estradiol, 1 microgram/kg body weight per day), which stimulate triglyceride production in normal women and those with endogenous hypertriglyceridemia, were found to exert a paradoxical, hypolipidemic effect in six subjects (five women, one man) with type III hyperlipoproteinemia on diets both of normal and of fat-free, high-carbohydrate composition. Moreover, very low-density (VLD) lipoprotein lipid and apolipoprotein composition and electrophoretic mobility became normal during estrogen administration in these subjects. Levels of normal VLD lipoproteins remained mildly to moderately elevated in a type IV lipoprotein pattern. Estrogen withdrawal promptly restored the type III pattern with its abnormal enrichment of VLD lipoproteins with apolipoprotein E (the arginine-rich peptide). These findings suggest that estrogens facilitate the assimilation of chylomicron and VLD lipoprotein remnants, a defect that appears likely to represent the metabolic abnormality underlying type III hyperlipoproteinemia."}
{"id": "PMID:200162", "title": "Primary type V hyperlipoproteinemia. A descriptive study in 32 families.", "content": "We have studied 32 kindreds identified by propositi with primary type V hyperlipoproteinemia. The clinical presentation, metabolic associations, and natural history confirm the distinctiveness of primary type V hyperlipoproteinemia from other lipoprotein abnormalities. Although the underlying defect(s) remains unknown, several factors such as obesity, alcohol, drugs, and diet are able to modify the glyceridemia, the major manifestation of this disorder. Abnormalities of postheparin lipolytic activity or its subfractions do not appear to be involved in the pathogenesis of primary type V. The prevalence of hyperuricemia, diabetes, pancreatitis, and xanthomatosis appears high among the 32 propositi; the last two entities are much less prevalent in the relatives, even among those relatives classified as hyperglyceridemic. There is no evidence in these families of excessive coronary artery disease prevalence. Triglyceride levels are positively associated with age in this population, especially among women. Average triglyceride levels were lower for women than for men before age 50.", "contents": "Primary type V hyperlipoproteinemia. A descriptive study in 32 families. We have studied 32 kindreds identified by propositi with primary type V hyperlipoproteinemia. The clinical presentation, metabolic associations, and natural history confirm the distinctiveness of primary type V hyperlipoproteinemia from other lipoprotein abnormalities. Although the underlying defect(s) remains unknown, several factors such as obesity, alcohol, drugs, and diet are able to modify the glyceridemia, the major manifestation of this disorder. Abnormalities of postheparin lipolytic activity or its subfractions do not appear to be involved in the pathogenesis of primary type V. The prevalence of hyperuricemia, diabetes, pancreatitis, and xanthomatosis appears high among the 32 propositi; the last two entities are much less prevalent in the relatives, even among those relatives classified as hyperglyceridemic. There is no evidence in these families of excessive coronary artery disease prevalence. Triglyceride levels are positively associated with age in this population, especially among women. Average triglyceride levels were lower for women than for men before age 50."}
{"id": "PMID:200166", "title": "Evacuation of orbital hematoma by continuous suction.", "content": "An orbital hematoma, unusual in its delayed onset and association with indirect trauma, is described. Successful therapy consisted of continuous suction through a polyethylene catheter. Various methods of therapy, conservative and surgical, have been described in the ophthalmic literature, but no previous report was found of the employment of continuous suction.", "contents": "Evacuation of orbital hematoma by continuous suction. An orbital hematoma, unusual in its delayed onset and association with indirect trauma, is described. Successful therapy consisted of continuous suction through a polyethylene catheter. Various methods of therapy, conservative and surgical, have been described in the ophthalmic literature, but no previous report was found of the employment of continuous suction."}
{"id": "PMID:200167", "title": "The deficiency of a lysosomal acid hydrolase in two clones derived from the human lymphoblastoid line F137 after mutagen treatment.", "content": "Two clones (out of a total of 181 clones tested) derived from the human lymphoblastoid (lymphoid) line F137 after mutagen treatment were found to be deficient in a lysosomal acid hydrolase. The clone N32 derived from EMS-treated F137 is deficient in N-acetyl hexosaminidase A and B but contains normal levels of N-acetyl hexosaminidase C and low levels of an enzyme resembling N-acetyl hexosaminidase S. Thus the enzyme deficiency in this clone appears to resemble the so-called Sandhoff variant of Tay-Sachs disease, a disease inherited as an autosomal recessive condition. The clone G3 derived from MNNG treated F137 is deficient in alpha-galactosidase A. This clone resembles the situation in X-linked Fabry's disease. Karyotype analysis of the clones failed to reveal any chromosome rearrangement or losses of chromosomal material that might have accounted for the mutations and it is suggested that a single point mutation might in each case account for the loss of enzyme activity. No storage of the natural substrates of the two enzymes could be demonstrated in the clones.", "contents": "The deficiency of a lysosomal acid hydrolase in two clones derived from the human lymphoblastoid line F137 after mutagen treatment. Two clones (out of a total of 181 clones tested) derived from the human lymphoblastoid (lymphoid) line F137 after mutagen treatment were found to be deficient in a lysosomal acid hydrolase. The clone N32 derived from EMS-treated F137 is deficient in N-acetyl hexosaminidase A and B but contains normal levels of N-acetyl hexosaminidase C and low levels of an enzyme resembling N-acetyl hexosaminidase S. Thus the enzyme deficiency in this clone appears to resemble the so-called Sandhoff variant of Tay-Sachs disease, a disease inherited as an autosomal recessive condition. The clone G3 derived from MNNG treated F137 is deficient in alpha-galactosidase A. This clone resembles the situation in X-linked Fabry's disease. Karyotype analysis of the clones failed to reveal any chromosome rearrangement or losses of chromosomal material that might have accounted for the mutations and it is suggested that a single point mutation might in each case account for the loss of enzyme activity. No storage of the natural substrates of the two enzymes could be demonstrated in the clones."}
{"id": "PMID:200168", "title": "Family studies with the chromosome 9 markers ABO, AK1, ACONs and 9qh.", "content": "We have failed to measure the recombination fraction between 9qh and the ABO:AK1 linkage group. Since the total male map distance along chromosome 9 is likely to be at least 120 cM, calculated from male chiasmata counts (Hult\u00e9n, 1974) they may well not be within measurable distance of each other. ACONs does not lie between ABO and AK1, but there is so little information on this marker from family studies that it could lie almost anywhere else on chromosome 9 and might be within measurable distance of 9qh. The map of chromosome 9 based on studies on families with normal karyotypes is summarized in Fig. 1. We hope to improve this map in a subsequent paper based on observations on families with abnormal karyotypes.", "contents": "Family studies with the chromosome 9 markers ABO, AK1, ACONs and 9qh. We have failed to measure the recombination fraction between 9qh and the ABO:AK1 linkage group. Since the total male map distance along chromosome 9 is likely to be at least 120 cM, calculated from male chiasmata counts (Hult\u00e9n, 1974) they may well not be within measurable distance of each other. ACONs does not lie between ABO and AK1, but there is so little information on this marker from family studies that it could lie almost anywhere else on chromosome 9 and might be within measurable distance of 9qh. The map of chromosome 9 based on studies on families with normal karyotypes is summarized in Fig. 1. We hope to improve this map in a subsequent paper based on observations on families with abnormal karyotypes."}
{"id": "PMID:200169", "title": "Lysosomal enzymes in human lymphoblastoid lines: unusual characteristics of RAJI and DAUDI.", "content": "The lysosomal enzymes N-acetyl hexosaminidase, alpha-galactosidase and alpha-mannosidase vary in electrophoretic mobility in different human lymphoblastoid (lymphoid) lines. The relative mobilities of these three enzymes and three out of four other lysosomal enzymes tested correlate well with each other. The patterns appear to be relatively stable characteristics of each line. The lines RAJI and DAUDI show a strikingly fast electrophoretic mobility for all of these enzymes. N-acetyl hexosaminidase is also markedly deficient in DAUDI.", "contents": "Lysosomal enzymes in human lymphoblastoid lines: unusual characteristics of RAJI and DAUDI. The lysosomal enzymes N-acetyl hexosaminidase, alpha-galactosidase and alpha-mannosidase vary in electrophoretic mobility in different human lymphoblastoid (lymphoid) lines. The relative mobilities of these three enzymes and three out of four other lysosomal enzymes tested correlate well with each other. The patterns appear to be relatively stable characteristics of each line. The lines RAJI and DAUDI show a strikingly fast electrophoretic mobility for all of these enzymes. N-acetyl hexosaminidase is also markedly deficient in DAUDI."}
{"id": "PMID:200170", "title": "Antiviral activity of ribavirin in rotavirus gastroenteritis of mice.", "content": "Ribavirin was inactive against the rotavirus of murine gastroenteritis; this may be due to the presence of guanosine inhibitors in the gut.", "contents": "Antiviral activity of ribavirin in rotavirus gastroenteritis of mice. Ribavirin was inactive against the rotavirus of murine gastroenteritis; this may be due to the presence of guanosine inhibitors in the gut."}
{"id": "PMID:200171", "title": "Growth properties of mecillinam-resistant bacterial variants in urine.", "content": "Resistant variants are often formed when susceptible Enterobacteriaceae are grown in media containing mecillinam. These variants have not yet been detected in patients or identified as a cause of treatment failure in limited clinical trials. Mecillinam-resistant organisms were formed by 5 out of 13 urinary isolates of Enterobacteriaceae incubated in urine containing mecillinam. The mean generation time of these five variants in urine containing therapeutic concentrations of mecillinam was 3.2 times that of normal organisms in antibiotic-free urine. When three of these five resistant variants were subcultured in antibiotic-free urine, the generation time, morphology, and antibiotic susceptibility returned to normal. On antibiotic-free agar medium, all five mecillinam-resistant variants readily reverted to the \"susceptible\" form and were therefore more likely to be phenotypic rather than genotypic mutants. In a second series of experiments, the flushing effect of the bladder on the clearance of organisms was partly simulated by frequent subculture in urine. Under these conditions, the cell density of cultures of all bacteria remained high during 10 subcultures over 52 h. However, bacterial populations progressively decreased in urine containing mecillinam until none could be detected at 28 h or thereafter. The slow growth rate of mecillinam-resistant variants may explain why detectable numbers of these organisms fail to colonize the urinary tract during treatment. Other factors may reinforce the postulated effect of the reduced growth rate in vivo.", "contents": "Growth properties of mecillinam-resistant bacterial variants in urine. Resistant variants are often formed when susceptible Enterobacteriaceae are grown in media containing mecillinam. These variants have not yet been detected in patients or identified as a cause of treatment failure in limited clinical trials. Mecillinam-resistant organisms were formed by 5 out of 13 urinary isolates of Enterobacteriaceae incubated in urine containing mecillinam. The mean generation time of these five variants in urine containing therapeutic concentrations of mecillinam was 3.2 times that of normal organisms in antibiotic-free urine. When three of these five resistant variants were subcultured in antibiotic-free urine, the generation time, morphology, and antibiotic susceptibility returned to normal. On antibiotic-free agar medium, all five mecillinam-resistant variants readily reverted to the \"susceptible\" form and were therefore more likely to be phenotypic rather than genotypic mutants. In a second series of experiments, the flushing effect of the bladder on the clearance of organisms was partly simulated by frequent subculture in urine. Under these conditions, the cell density of cultures of all bacteria remained high during 10 subcultures over 52 h. However, bacterial populations progressively decreased in urine containing mecillinam until none could be detected at 28 h or thereafter. The slow growth rate of mecillinam-resistant variants may explain why detectable numbers of these organisms fail to colonize the urinary tract during treatment. Other factors may reinforce the postulated effect of the reduced growth rate in vivo."}
{"id": "PMID:200172", "title": "Latent herpes simplex virus infections in sensory ganglia of mice after topical treatment with adenine arabinoside and adenine arabinoside monophosphate.", "content": "Adenine arabinoside (Ara-A) and Ara-A monosphosphate (Ara-AMP) ointments were able to prevent the fatal outcome of herpes simplex virus (HSV)-induced skin infection of the lumbosacral area in hairless mice. Ara-A and Ara-AMP had no irritating effect on the skin, but in a number of animals a protracted healing time of the skin lesions after the treatment was observed. The compounds conferred only a partial protection against the establishment of latent HSV infection in the spinal root ganglia of the treated animals. The immune response, as judged from levels of HSV-specific neutralizing serum antibody titers, was not impaired by the antiviral treatment.", "contents": "Latent herpes simplex virus infections in sensory ganglia of mice after topical treatment with adenine arabinoside and adenine arabinoside monophosphate. Adenine arabinoside (Ara-A) and Ara-A monosphosphate (Ara-AMP) ointments were able to prevent the fatal outcome of herpes simplex virus (HSV)-induced skin infection of the lumbosacral area in hairless mice. Ara-A and Ara-AMP had no irritating effect on the skin, but in a number of animals a protracted healing time of the skin lesions after the treatment was observed. The compounds conferred only a partial protection against the establishment of latent HSV infection in the spinal root ganglia of the treated animals. The immune response, as judged from levels of HSV-specific neutralizing serum antibody titers, was not impaired by the antiviral treatment."}
{"id": "PMID:200173", "title": "Production of uricase by Candida tropicalis using n-alkane as a substrate.", "content": "Production of uricase (urate oxidase, EC 1.7.3.3) by n-alkane-utilizing Candida tropicalis pK233 was studied. Although the yeast showed very low enzyme productivity under growing conditions on glucose or an n-alkane mixture (C10 to C13) (less than 2 U/g of dry cells), enzyme formation was enhanced markedly in an induction medium consisting of potassium phosphate buffer, MgSO4, uric acid, and an n-alkane mixture (47 U/g of dry cells) or glucose (21 U/g of dry cells). Of the carbon sources tested, the n-alkane mixture was the most suitable for enzyme production. Appropriate aeration also stimulated uricase formation. In addition to uric acid, xanthine, guanine, adenine, and hypoxanthine were also effective for inducing uricase. Under optimum conditions, the maximum yield of the enzyme was 91 U/g of dry cells. Uricase thus induced was localized in the microbodies of the yeast.", "contents": "Production of uricase by Candida tropicalis using n-alkane as a substrate. Production of uricase (urate oxidase, EC 1.7.3.3) by n-alkane-utilizing Candida tropicalis pK233 was studied. Although the yeast showed very low enzyme productivity under growing conditions on glucose or an n-alkane mixture (C10 to C13) (less than 2 U/g of dry cells), enzyme formation was enhanced markedly in an induction medium consisting of potassium phosphate buffer, MgSO4, uric acid, and an n-alkane mixture (47 U/g of dry cells) or glucose (21 U/g of dry cells). Of the carbon sources tested, the n-alkane mixture was the most suitable for enzyme production. Appropriate aeration also stimulated uricase formation. In addition to uric acid, xanthine, guanine, adenine, and hypoxanthine were also effective for inducing uricase. Under optimum conditions, the maximum yield of the enzyme was 91 U/g of dry cells. Uricase thus induced was localized in the microbodies of the yeast."}
{"id": "PMID:200184", "title": "Granular cell myoblastoma in Nigerian Igbos.", "content": "Three cases of granular cell myoblastoma occurring in the Igbos of Nigeria are reported. In this ethnic group the tumor has shown several typical features as follows: it is rarely diagnosed preoperatively; it is found more frequently in the oral cavity and breast than in most other sites; and it is in the maxilla of girls that it usually presents congenitally. A unique presentation in this ethnic group occurred in the perineum. The lesion found in this site appears to be the first to be reported in the literature.", "contents": "Granular cell myoblastoma in Nigerian Igbos. Three cases of granular cell myoblastoma occurring in the Igbos of Nigeria are reported. In this ethnic group the tumor has shown several typical features as follows: it is rarely diagnosed preoperatively; it is found more frequently in the oral cavity and breast than in most other sites; and it is in the maxilla of girls that it usually presents congenitally. A unique presentation in this ethnic group occurred in the perineum. The lesion found in this site appears to be the first to be reported in the literature."}
{"id": "PMID:200185", "title": "Three cases of rare tumors of the mammary gland.", "content": "The cases are reported of three patients with rare tumors of the mammary gland: one osteogenic sarcoma, one benign mixed tumor and one reticulum-cell sarcoma of the breast. The pathological and clinical aspects of these tumors are discussed with reference to the literature.", "contents": "Three cases of rare tumors of the mammary gland. The cases are reported of three patients with rare tumors of the mammary gland: one osteogenic sarcoma, one benign mixed tumor and one reticulum-cell sarcoma of the breast. The pathological and clinical aspects of these tumors are discussed with reference to the literature."}
{"id": "PMID:200188", "title": "Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. II. Swelling.", "content": "Studies of the equilibrium, partition, and diffusion of tritiated water were carried out on normal and osteoarthrotic cartilage as well as on cartilage from which proteoglycans had been extracted chemically. All the water was found to be freely exchangeable in both normal and degenerate specimens. The diffusiviity of the water was equal to about 40% of the value in free solution, with an activation energy equal to that in free solution. It was concluded that the swelling of degenerate tissue is not due to any changes in the state of the water, but to a failure of the damaged collagen network to oppose the swelling pressure of the proteoglycans. Swelling similar to that observed in fibrillated cartilage was also found in initially normal specimens treated with collagenase.", "contents": "Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. II. Swelling. Studies of the equilibrium, partition, and diffusion of tritiated water were carried out on normal and osteoarthrotic cartilage as well as on cartilage from which proteoglycans had been extracted chemically. All the water was found to be freely exchangeable in both normal and degenerate specimens. The diffusiviity of the water was equal to about 40% of the value in free solution, with an activation energy equal to that in free solution. It was concluded that the swelling of degenerate tissue is not due to any changes in the state of the water, but to a failure of the damaged collagen network to oppose the swelling pressure of the proteoglycans. Swelling similar to that observed in fibrillated cartilage was also found in initially normal specimens treated with collagenase."}
{"id": "PMID:200190", "title": "The influence of various methods of sensitization on delayed hypersensitivity to Bordetella pertussis in the Sprague Dawley Rat.", "content": "In the rat, the injection of Bordetella pertussis produces, after prior sensitization, a delayed hypersensitivity inflammatory reaction within the pleural cavity. The influence of various methods of sensitization on this hypersensitivity was studied in the Sprague Dawley rat. The reaction was very variable according to the experimental conditions used. Optimal sensitization was obtained following the injection of antigen mixed with complete Freund's adjuvant into the dorsal surface of the paws.", "contents": "The influence of various methods of sensitization on delayed hypersensitivity to Bordetella pertussis in the Sprague Dawley Rat. In the rat, the injection of Bordetella pertussis produces, after prior sensitization, a delayed hypersensitivity inflammatory reaction within the pleural cavity. The influence of various methods of sensitization on this hypersensitivity was studied in the Sprague Dawley rat. The reaction was very variable according to the experimental conditions used. Optimal sensitization was obtained following the injection of antigen mixed with complete Freund's adjuvant into the dorsal surface of the paws."}
{"id": "PMID:200191", "title": "Influence of cyclic nucleotides and a phosphodiesterase inhibitor on in vitro human blood neutrophil chemotaxis.", "content": "Cyclic AMP and dibutyryl cyclic AMP as well as several 8-substituted analogs of cyclic AMP inhibited in vitro human blood neutrophil chemotaxis. Cyclic GMP enhanced chemotaxis. 8-substitution on the cyclic GMP nucleus markedly dampened the cyclic GMP effect. SQ 20,009, a potent phosphodiesterase inhibitor when tested alone inhibited chemotaxis; it potentiated the inhibition or enhancement of chemotaxis when combined with cyclic AMP or cyclic GMP, respectively.", "contents": "Influence of cyclic nucleotides and a phosphodiesterase inhibitor on in vitro human blood neutrophil chemotaxis. Cyclic AMP and dibutyryl cyclic AMP as well as several 8-substituted analogs of cyclic AMP inhibited in vitro human blood neutrophil chemotaxis. Cyclic GMP enhanced chemotaxis. 8-substitution on the cyclic GMP nucleus markedly dampened the cyclic GMP effect. SQ 20,009, a potent phosphodiesterase inhibitor when tested alone inhibited chemotaxis; it potentiated the inhibition or enhancement of chemotaxis when combined with cyclic AMP or cyclic GMP, respectively."}
{"id": "PMID:200192", "title": "Bilateral diaphragmatic paralysis in association with neurogenic disease.", "content": "A patient had complete diaphragmatic paralysis and his disease progressed to include systemic neurological deficit. The cause is unknown. Appropriate diagnostic tests are emphasized, and a discussion of potential etiologies with a review of the literature of idiopathic diaphragmatic paralysis is presented.", "contents": "Bilateral diaphragmatic paralysis in association with neurogenic disease. A patient had complete diaphragmatic paralysis and his disease progressed to include systemic neurological deficit. The cause is unknown. Appropriate diagnostic tests are emphasized, and a discussion of potential etiologies with a review of the literature of idiopathic diaphragmatic paralysis is presented."}
{"id": "PMID:200193", "title": "Spontaneous cytomegalovirus mononucleosis with conjunctivitis.", "content": "Cytomegalovirus (CMV) was isolated from the conjunctiva of a patient with mild unilateral catarrhal conjunctivitis associated with the typical clinical features of CMV mononucleosis syndrome in a previously healthy adult. The diagnosis was confirmed by a marked rise in the complement fixation antibody titers. Prospective studies are needed to determine the frequency of conjunctival involvement in CMV mononucleosis and the relation, if any, to sporadic cases of conjunctivitis.", "contents": "Spontaneous cytomegalovirus mononucleosis with conjunctivitis. Cytomegalovirus (CMV) was isolated from the conjunctiva of a patient with mild unilateral catarrhal conjunctivitis associated with the typical clinical features of CMV mononucleosis syndrome in a previously healthy adult. The diagnosis was confirmed by a marked rise in the complement fixation antibody titers. Prospective studies are needed to determine the frequency of conjunctival involvement in CMV mononucleosis and the relation, if any, to sporadic cases of conjunctivitis."}
{"id": "PMID:200194", "title": "Qualitative x-ray spectrometric study of E. histolytica trophozoite nuclei.", "content": "Qualitative X-ray energy spectroscopical analysis was performed in two strains of Entamoeba histolytica trophozoites: HK-9; NIH strain, and HM-2; IMSS strain, cultured in axenic and monoxenic conditions, respectively. The trophozoites were fixed in buffered-glutaraldehyde, embedded in Epon, thick sectioned )50-200 nm), and mounted on nickel grids. X-ray emissions were analyzed with an Ortec X-ray energy detector and multichannel and analyzer adapted to a transmission electron microscope. The study was concentrated on the refractive intranuclear bodies, characteristically numerous in axenically grown E. histolytica trophozoites. Nuclei of trophozoites with those intranuclear bodies contained phosphorus, calcium, and magnesium in greater amounts than nuclei not containing those structures. This was true for all axenically grown trophozoites and two monoxenically grown trophozoites which contained four intranuclear bodies. It is concluded that the composition of the refractive intranuclear bodies in E. histolytica trophozites does not appear to change with the culture conditions or with the composition of the culture media.", "contents": "Qualitative x-ray spectrometric study of E. histolytica trophozoite nuclei. Qualitative X-ray energy spectroscopical analysis was performed in two strains of Entamoeba histolytica trophozoites: HK-9; NIH strain, and HM-2; IMSS strain, cultured in axenic and monoxenic conditions, respectively. The trophozoites were fixed in buffered-glutaraldehyde, embedded in Epon, thick sectioned )50-200 nm), and mounted on nickel grids. X-ray emissions were analyzed with an Ortec X-ray energy detector and multichannel and analyzer adapted to a transmission electron microscope. The study was concentrated on the refractive intranuclear bodies, characteristically numerous in axenically grown E. histolytica trophozoites. Nuclei of trophozoites with those intranuclear bodies contained phosphorus, calcium, and magnesium in greater amounts than nuclei not containing those structures. This was true for all axenically grown trophozoites and two monoxenically grown trophozoites which contained four intranuclear bodies. It is concluded that the composition of the refractive intranuclear bodies in E. histolytica trophozites does not appear to change with the culture conditions or with the composition of the culture media."}
{"id": "PMID:200195", "title": "Routine titration of foot-and-mouth disease virus suspensions by analytical ultracentrifugation 2nd communication: sedimentation equilibrium method.", "content": "A routine method for the determination of the virus concentration in FMD virus cultures and vaccines was developed. This method was based on sedimentation equilibrium in the analytical ultraviolet scanning ultracentrifuge. The virus suspension was first clarified. The virions were then sedimented in a preparative ultracentrifuge. The resuspended virions were diluted in a Cesium chloride solution and brought to equilibrium in the density gradient generated in the analytical ultracentrifuge. The optical density of the virus band was measured by the UV scanning system. A calculation procedure was developed to compute the density at the limits and at the maximum of the virus band. The virus concentration expressed as weight, was calculated for the original virus suspension.", "contents": "Routine titration of foot-and-mouth disease virus suspensions by analytical ultracentrifugation 2nd communication: sedimentation equilibrium method. A routine method for the determination of the virus concentration in FMD virus cultures and vaccines was developed. This method was based on sedimentation equilibrium in the analytical ultraviolet scanning ultracentrifuge. The virus suspension was first clarified. The virions were then sedimented in a preparative ultracentrifuge. The resuspended virions were diluted in a Cesium chloride solution and brought to equilibrium in the density gradient generated in the analytical ultracentrifuge. The optical density of the virus band was measured by the UV scanning system. A calculation procedure was developed to compute the density at the limits and at the maximum of the virus band. The virus concentration expressed as weight, was calculated for the original virus suspension."}
{"id": "PMID:200198", "title": "Location of antigens associated with bovine leukemia virus.", "content": "Antigens associated with bovine leukemia virus (BLV) infection (gp 44/55 and p23) were identified by neutralization and immunofluorescent antibody (FA) tests. Only serums containing antibody to gp 45/55 neutralized the virus; antibody to p23 did not. These results indicate that gp 44/55 may be located in the virus envelope. In indirect FA tests, both a cytoplasmic fluorescence and a membrane fluorscence were detected in BLV-infected cells. The serum used in the FA test was then absorbed with either p23 or gp 45/55. The results of these absorption tests indicate that the membrane fluorescence maybe associated with gp 45/55 and the cytoplasmic fluorescence may be associated with p23.", "contents": "Location of antigens associated with bovine leukemia virus. Antigens associated with bovine leukemia virus (BLV) infection (gp 44/55 and p23) were identified by neutralization and immunofluorescent antibody (FA) tests. Only serums containing antibody to gp 45/55 neutralized the virus; antibody to p23 did not. These results indicate that gp 44/55 may be located in the virus envelope. In indirect FA tests, both a cytoplasmic fluorescence and a membrane fluorscence were detected in BLV-infected cells. The serum used in the FA test was then absorbed with either p23 or gp 45/55. The results of these absorption tests indicate that the membrane fluorescence maybe associated with gp 45/55 and the cytoplasmic fluorescence may be associated with p23."}
{"id": "PMID:200199", "title": "Inhibition of bovine leukemia virus release by antiviral antibodies.", "content": "Peripheral blood lymphocytes from bovine leukemia virus (BLV) infected cattle were grown in vitro with serums from BLV-infected and uninfected cattle, sheep and rabbits. Only serums from infected animals which had antibody to gp 45/55, the major glycoprotein antigen, inhibited the release of virus from the cells. Although viral antigens could be detected in the cells themselves, none were detected in the supernatants of cultures grown with these serums. Normal serums and serums with antibody only to p23, the internal BLV antigen, did not inhibit virus release. To identify the factor responsible for virus release inhibition, 2 inhibitory serums were absorbed with either gp 44/55, p23 or tissue culture cells from BLV-infected and uninfected cells lines. The results indicated that antibody to gp 45/55 is the factor responsible for virus release inhibition.", "contents": "Inhibition of bovine leukemia virus release by antiviral antibodies. Peripheral blood lymphocytes from bovine leukemia virus (BLV) infected cattle were grown in vitro with serums from BLV-infected and uninfected cattle, sheep and rabbits. Only serums from infected animals which had antibody to gp 45/55, the major glycoprotein antigen, inhibited the release of virus from the cells. Although viral antigens could be detected in the cells themselves, none were detected in the supernatants of cultures grown with these serums. Normal serums and serums with antibody only to p23, the internal BLV antigen, did not inhibit virus release. To identify the factor responsible for virus release inhibition, 2 inhibitory serums were absorbed with either gp 44/55, p23 or tissue culture cells from BLV-infected and uninfected cells lines. The results indicated that antibody to gp 45/55 is the factor responsible for virus release inhibition."}
{"id": "PMID:200200", "title": "Effect of tunicamyein on the morphogenesis of Semliki Forest virus and Rous sarcoma virus.", "content": "Semliki Forst Virus (SFV) infected chick embroyo cells (CEC) incubated in the presence of Tunicamyein, a drug which specifically inhibits glycosylation, were studied under the electron microscope. No extracellular virions were produced although intracellular viral nucleocapsids in paracrystalline form were detected. Under these conditions the structures, referred to as type 1 and 2 cytopathic vacuoles (cpv-1 and cpv-2, respectively) as well as membraneous spherules at the plasma membrane could still be observed. CEC rpoductively infected and transformed by Rous sarcoma virus (RSV) incubated for 24 hours in the presence of Tunicamycin (1 microgram/ml) still showed budding and extracellular parties. Intracellur nucleocapsid could could not be detected.", "contents": "Effect of tunicamyein on the morphogenesis of Semliki Forest virus and Rous sarcoma virus. Semliki Forst Virus (SFV) infected chick embroyo cells (CEC) incubated in the presence of Tunicamyein, a drug which specifically inhibits glycosylation, were studied under the electron microscope. No extracellular virions were produced although intracellular viral nucleocapsids in paracrystalline form were detected. Under these conditions the structures, referred to as type 1 and 2 cytopathic vacuoles (cpv-1 and cpv-2, respectively) as well as membraneous spherules at the plasma membrane could still be observed. CEC rpoductively infected and transformed by Rous sarcoma virus (RSV) incubated for 24 hours in the presence of Tunicamycin (1 microgram/ml) still showed budding and extracellular parties. Intracellur nucleocapsid could could not be detected."}
{"id": "PMID:200202", "title": "The polypeptide composition of avain infectious bronchitis virus particles.", "content": "Egg grown avian infectious bronchitis virus (IBV) centrifuged on sucrose density gradients was found to consist of a major virus peak of density 1.17 to 1.18 g/cm(3). Three different IBV strains were examined and no morphological differences were detected between virus particles of different densities or from different strains. The polypeptides of the different density virus particles from the three IBV strains were analysed on polyacrylamide gels. In all cases 7 polypeptides were observed, although there were differences in the proportions of these polypeptides in particles of different densities and those from the different strains. The polypeptides have been called VP1 (molecular weight 130,000), VP2 (105,000), VP3 (97,000), VP4 (81,000), VP5 (74,000), VP6 (51,000) and VP7 (33,000). Additional polypeptides were produced if slightly harsher treatments were used.", "contents": "The polypeptide composition of avain infectious bronchitis virus particles. Egg grown avian infectious bronchitis virus (IBV) centrifuged on sucrose density gradients was found to consist of a major virus peak of density 1.17 to 1.18 g/cm(3). Three different IBV strains were examined and no morphological differences were detected between virus particles of different densities or from different strains. The polypeptides of the different density virus particles from the three IBV strains were analysed on polyacrylamide gels. In all cases 7 polypeptides were observed, although there were differences in the proportions of these polypeptides in particles of different densities and those from the different strains. The polypeptides have been called VP1 (molecular weight 130,000), VP2 (105,000), VP3 (97,000), VP4 (81,000), VP5 (74,000), VP6 (51,000) and VP7 (33,000). Additional polypeptides were produced if slightly harsher treatments were used."}
{"id": "PMID:200203", "title": "Detection of transmissible gastroenteritis virus neutralising antibody in cats.", "content": "High titres of neutralizing activity to transmissible gastroenteritis virus (TGEV), a porcine coronavirus, were found in sera and peritoneal fluids from cats infected with feline infectious peritonitis (FIP). A small proportion of cats, from a hospital population unaffected by FIP, also had neutralising activity. Procedures to remove non-specific viral inhibitors, including treatment by heat inactivation, trypsin, sulphydryl reagent and kaolin absorption were unsuccessful. The active component was unable to neutralise another porcine coronavirus, haemagglutinating encephalomyelitis virus or the porcine enterovirus, Talfan. Gel filtration of feline sera and peritoneal fluid demonstrated high levels of the neutralising activity in the area corresponding to 7S IgG, which could be removed by absorption with specific anti-IgG serum and these properties are suggested to be consistent with those of antibody. These findings imply that there is a coronavirus in cats which is antigenically related to TGEV and its possible nature is discussed.", "contents": "Detection of transmissible gastroenteritis virus neutralising antibody in cats. High titres of neutralizing activity to transmissible gastroenteritis virus (TGEV), a porcine coronavirus, were found in sera and peritoneal fluids from cats infected with feline infectious peritonitis (FIP). A small proportion of cats, from a hospital population unaffected by FIP, also had neutralising activity. Procedures to remove non-specific viral inhibitors, including treatment by heat inactivation, trypsin, sulphydryl reagent and kaolin absorption were unsuccessful. The active component was unable to neutralise another porcine coronavirus, haemagglutinating encephalomyelitis virus or the porcine enterovirus, Talfan. Gel filtration of feline sera and peritoneal fluid demonstrated high levels of the neutralising activity in the area corresponding to 7S IgG, which could be removed by absorption with specific anti-IgG serum and these properties are suggested to be consistent with those of antibody. These findings imply that there is a coronavirus in cats which is antigenically related to TGEV and its possible nature is discussed."}
{"id": "PMID:200206", "title": "Ocular manifestations of focal dermal hypoplasia syndrome.", "content": "Although 40 percent of patients with the focal dermal hypoplasia syndrome have ocular abnormalities, to our knowledge, only one case of this condition has been previously described in the ophthalmic literature. Two additional cases are presented, and the systemic and ocular findings are reviewed.", "contents": "Ocular manifestations of focal dermal hypoplasia syndrome. Although 40 percent of patients with the focal dermal hypoplasia syndrome have ocular abnormalities, to our knowledge, only one case of this condition has been previously described in the ophthalmic literature. Two additional cases are presented, and the systemic and ocular findings are reviewed."}
{"id": "PMID:200207", "title": "Malignant fibrous histiocytoma of the orbit.", "content": "A 31-year-old woman had a mass in the posterior inferior orbit that progressively increased in size for almost two years. Histopathologic examination of an orbital biopsy specimen showed pleomorphic neoplastic cells arranged in a storiform pattern. The tumor cells were composed of hyperchromatic nuclei with prominent nucleoli and admixtures of fibroblasts. Electron microscopy demonstrated histiocyte-like cells with complex infoldings of plasma membrane, prominent mitochondria and golgi, and free ribosomes. Fibroblast-like cells displayed abundant rough endoplasmic reticulum and adjacent collagen fibrils. The diagnosis was malignant fibrous histiocytoma. An exenteration was performed and postoperative systemic chemotherapy with doxorubicin hydrochloride and methotrexate sodium sulfate was commenced. There was no evidence of recurrence two years later.", "contents": "Malignant fibrous histiocytoma of the orbit. A 31-year-old woman had a mass in the posterior inferior orbit that progressively increased in size for almost two years. Histopathologic examination of an orbital biopsy specimen showed pleomorphic neoplastic cells arranged in a storiform pattern. The tumor cells were composed of hyperchromatic nuclei with prominent nucleoli and admixtures of fibroblasts. Electron microscopy demonstrated histiocyte-like cells with complex infoldings of plasma membrane, prominent mitochondria and golgi, and free ribosomes. Fibroblast-like cells displayed abundant rough endoplasmic reticulum and adjacent collagen fibrils. The diagnosis was malignant fibrous histiocytoma. An exenteration was performed and postoperative systemic chemotherapy with doxorubicin hydrochloride and methotrexate sodium sulfate was commenced. There was no evidence of recurrence two years later."}
{"id": "PMID:200208", "title": "Herpesvirus in sensory and autonomic ganglia after eye infection.", "content": "In herpesvirus hominis (HVH) infections, virus harbored in the sensory ganglia is now thought to be the main source of recurrent infection at peripheral sites. Experimental HVH infection of the external eye in rabbits produces an acute infection and then latent infection of the trigeminal ganglion. In this study, acute infection of the automatic ganglia serving the eye (superior cervical and ciliary) as well as trigeminal ganglia occurred after HVH inoculation of rabbits' corneas with a herpes type 1 strain (RE). Latent virus infection was detected in the trigeminal ganglion of one of five animals tested six months after initial infection. Since the superior cervical and other autonomic ganglia serving the eye become infected during acute herpes simplex virus infection of the external eye in rabbits, it is possible that these ganglia are also sources of reinfection in recurrent herpetic disease of the eye. Following the initial eye disease with this virus strain, HVH shedding could not be demonstrated even after induction attempts by topically applied epinephrine or systemic use of cyclophosphamide. Thus, establishment of latent HVH infection in the ganglia and chronic shedding of virus into the external eye is not a constant feature of this animal model, but may depend on the specific strain of herpesvirus used.", "contents": "Herpesvirus in sensory and autonomic ganglia after eye infection. In herpesvirus hominis (HVH) infections, virus harbored in the sensory ganglia is now thought to be the main source of recurrent infection at peripheral sites. Experimental HVH infection of the external eye in rabbits produces an acute infection and then latent infection of the trigeminal ganglion. In this study, acute infection of the automatic ganglia serving the eye (superior cervical and ciliary) as well as trigeminal ganglia occurred after HVH inoculation of rabbits' corneas with a herpes type 1 strain (RE). Latent virus infection was detected in the trigeminal ganglion of one of five animals tested six months after initial infection. Since the superior cervical and other autonomic ganglia serving the eye become infected during acute herpes simplex virus infection of the external eye in rabbits, it is possible that these ganglia are also sources of reinfection in recurrent herpetic disease of the eye. Following the initial eye disease with this virus strain, HVH shedding could not be demonstrated even after induction attempts by topically applied epinephrine or systemic use of cyclophosphamide. Thus, establishment of latent HVH infection in the ganglia and chronic shedding of virus into the external eye is not a constant feature of this animal model, but may depend on the specific strain of herpesvirus used."}
{"id": "PMID:200209", "title": "Herpes simplex uveitis in immune rabbits. Priming effect of nonherpetic uveitis.", "content": "Systemic immunization of rabbits with herpes simplex virus (HSV) had two opposite effects on the outcome of subsequent efforts to produce primary HSV uveitis, the difference depending on whether or not the rabbits had had nonherpetic uveitis before the HSV challenge. In normal eyes, systemic immunization with HSV provided complete protection against the production of primary uveitis by an intraocular injection of HSV; but in eyes that had had a bout of experimentally induced nonherpetic uveitis before the challenge, the same systemic immunization was not protective. In these eyes, an immune-mediated uveal inflammation developed. Nonherpetic uveitis had apparently \"primed\" the eyes of the HSV-immune rabbits for subsequent immune-mediated HSV uveitis.", "contents": "Herpes simplex uveitis in immune rabbits. Priming effect of nonherpetic uveitis. Systemic immunization of rabbits with herpes simplex virus (HSV) had two opposite effects on the outcome of subsequent efforts to produce primary HSV uveitis, the difference depending on whether or not the rabbits had had nonherpetic uveitis before the HSV challenge. In normal eyes, systemic immunization with HSV provided complete protection against the production of primary uveitis by an intraocular injection of HSV; but in eyes that had had a bout of experimentally induced nonherpetic uveitis before the challenge, the same systemic immunization was not protective. In these eyes, an immune-mediated uveal inflammation developed. Nonherpetic uveitis had apparently \"primed\" the eyes of the HSV-immune rabbits for subsequent immune-mediated HSV uveitis."}
{"id": "PMID:200210", "title": "Acute peripheral facial palsy. Part of a cranial polyneuropathy?", "content": "In 14 of 16 consecutive patients with acute peripheral facial palsy, one or more (up to four) other nerves were involved. The nerves affected in addition to the facial nerve were as follows: trigeminal (ten patients), vestibular (eight), cochlear (six), vagus (one), and upper cervical (five). Virus was not isolated from any of the patients. A fourfold increase or decrease in complement-fixing antibody titers was present in eight patients (in four, varicella-zoster; in one, varicella-zoster and mumps; in two, cytomegalovirus; in one, mumps). Further, two of the patients with varicella-zoster antibodies showed clinical signs of herpes zoster oticus. About one fourth of all patients had an increase of ESR and of alpha2-globulins in serum, and two thirds of them had increased gamma-globulins in CSF. Acute peripheral facial palsy seems to be part of a cranial polyneuropathy and may be caused by a viral infection.", "contents": "Acute peripheral facial palsy. Part of a cranial polyneuropathy? In 14 of 16 consecutive patients with acute peripheral facial palsy, one or more (up to four) other nerves were involved. The nerves affected in addition to the facial nerve were as follows: trigeminal (ten patients), vestibular (eight), cochlear (six), vagus (one), and upper cervical (five). Virus was not isolated from any of the patients. A fourfold increase or decrease in complement-fixing antibody titers was present in eight patients (in four, varicella-zoster; in one, varicella-zoster and mumps; in two, cytomegalovirus; in one, mumps). Further, two of the patients with varicella-zoster antibodies showed clinical signs of herpes zoster oticus. About one fourth of all patients had an increase of ESR and of alpha2-globulins in serum, and two thirds of them had increased gamma-globulins in CSF. Acute peripheral facial palsy seems to be part of a cranial polyneuropathy and may be caused by a viral infection."}
{"id": "PMID:200212", "title": "Preweaning mortality in the pig. Pathological findings in piglets dying between birth and weaning.", "content": "During a survey of preweaning mortality 538 piglets which died between birth and weaning were autopsied. The results of laboratory examinations permitted a division of the findings into a number of syndromes which were considered to be associated with the immediate cause of death. The non-infectious conditions such as trauma, starvation and suffocation were the most common. Seventy-eight piglets were included in the trauma group because of depressed cranial bone fractures or visceral rupture leading to haemorrhage into the serous cavities. An absence of alimentary tract contents was detected in each of the 92 cases of starvation, fatty metamorphosis of the liver was found in 28 while the hepatocyte cytoplasm of the remainder stained uniformally. Cyanosis and visceral congestion and haemorrhage were the main features observed in the 159 deaths ascribed to suffocation. Bacterial septicaemias and infections with enterotoxic strains of E. coli were the most prevalent infectious conditions. E. coli and beta haemolytic streptococci were the most common causes of septicaemia, being isolated from 36 and 25 cases, respectively. The post-mortem findings in these cases were non-specific except for fibrinous polyserositis which was observed in 11 of the carcasses from which E. coli was recovered. Twenty-six piglets yielded E. coli in heavy pure culture from the upper small intestine and the most common serogroup involved was 08. Encephalomyocarditis virus infection was associated with the deaths of 19 piglets. Pathologically, it was characterised by myocardial degeneration and a variable influx of mononuclear inflammatory cells. No significant lesions were found in 41 piglets.", "contents": "Preweaning mortality in the pig. Pathological findings in piglets dying between birth and weaning. During a survey of preweaning mortality 538 piglets which died between birth and weaning were autopsied. The results of laboratory examinations permitted a division of the findings into a number of syndromes which were considered to be associated with the immediate cause of death. The non-infectious conditions such as trauma, starvation and suffocation were the most common. Seventy-eight piglets were included in the trauma group because of depressed cranial bone fractures or visceral rupture leading to haemorrhage into the serous cavities. An absence of alimentary tract contents was detected in each of the 92 cases of starvation, fatty metamorphosis of the liver was found in 28 while the hepatocyte cytoplasm of the remainder stained uniformally. Cyanosis and visceral congestion and haemorrhage were the main features observed in the 159 deaths ascribed to suffocation. Bacterial septicaemias and infections with enterotoxic strains of E. coli were the most prevalent infectious conditions. E. coli and beta haemolytic streptococci were the most common causes of septicaemia, being isolated from 36 and 25 cases, respectively. The post-mortem findings in these cases were non-specific except for fibrinous polyserositis which was observed in 11 of the carcasses from which E. coli was recovered. Twenty-six piglets yielded E. coli in heavy pure culture from the upper small intestine and the most common serogroup involved was 08. Encephalomyocarditis virus infection was associated with the deaths of 19 piglets. Pathologically, it was characterised by myocardial degeneration and a variable influx of mononuclear inflammatory cells. No significant lesions were found in 41 piglets."}
{"id": "PMID:200213", "title": "Studies on poxvirus isolated from a magpig in Queensland.", "content": "An avian poxvirus was isolated from a black-backed magpie in Queensland. The virus produced pocks on the chorio-allantoic membrane of chicken embryos and lesions on the skin of chickens. Comparison by passive haemagglutination test and neutralisation test indicated that the virus was related more closely to pigeonpox virus than to fowlpox virus.", "contents": "Studies on poxvirus isolated from a magpig in Queensland. An avian poxvirus was isolated from a black-backed magpie in Queensland. The virus produced pocks on the chorio-allantoic membrane of chicken embryos and lesions on the skin of chickens. Comparison by passive haemagglutination test and neutralisation test indicated that the virus was related more closely to pigeonpox virus than to fowlpox virus."}
{"id": "PMID:200214", "title": "Intracardial gas bubbles of altitude after negative pressure breathing.", "content": "The influence of negative pressure breathing on the appearance of intracardial gas bubbles at a subsequent decompression to altitude was investigated in five subjects using the precordial Doppler ultrasound technique. Every subject was tested for a suitable exposition that, after 30 min oxygen breathing at surface, caused both intracardial bubbles and decompression sickness. An identical exposition followed a week later, except that oxygen breathing at the surface now included negative pressure breathing. In all cases, negative pressure breathing caused a delay of the onset of both intracardial bubbles and bends and, in some cases, neither bubbles nor bends appeared at all. The total amount of bubbles was always less after negative pressure breathing. Thus, negative pressure breathing in connection with decompression may reduce the amount of intracardial bubbles and the risk of decompression sickness. This may be of importance in diving procedures and in the construction of diving devices.", "contents": "Intracardial gas bubbles of altitude after negative pressure breathing. The influence of negative pressure breathing on the appearance of intracardial gas bubbles at a subsequent decompression to altitude was investigated in five subjects using the precordial Doppler ultrasound technique. Every subject was tested for a suitable exposition that, after 30 min oxygen breathing at surface, caused both intracardial bubbles and decompression sickness. An identical exposition followed a week later, except that oxygen breathing at the surface now included negative pressure breathing. In all cases, negative pressure breathing caused a delay of the onset of both intracardial bubbles and bends and, in some cases, neither bubbles nor bends appeared at all. The total amount of bubbles was always less after negative pressure breathing. Thus, negative pressure breathing in connection with decompression may reduce the amount of intracardial bubbles and the risk of decompression sickness. This may be of importance in diving procedures and in the construction of diving devices."}
{"id": "PMID:200216", "title": "[The fructose induces \"glycogenosis\". III. Histochemical and morphometrical studies of glycogen metabolism in mouse liver after fructose overload (author's transl)].", "content": "After feeding fructose for 7 days rat liver cells show an accumulation of glycogen, a high activity of glucose-6-phosphatase combined with a SER- and RER-reduction. This result was reviewed by mouse liver cells using histochemical and morphometrical methods. 60% fructose in drinking water was given mice as only nutritional source. Controls had free access to Altromin-R-standard diet and drinking water. Glycogen and glycogen metabolizing enzymes are demonstrated in the course of an 1-14 days fructose diet. After a 7 days diet liver tissue was analysed morphometrically. Feeding of fructose leads to a high glycogen content, combined with a high activity of glycogen-phosphorylase and glucose-6-phosphatase in the liver parenchyma of mouse. Glycogen-synthetase activity falls to a low level. The SER and RER and the peroxisomes are reduced. The single volume of the hepatic nucleus is decreased and the hepatocellular chondrioma is transformed in a smaller number of larger mitochondria. Compared with the rate the analysed organelles and enzymes of mouse liver show only slight quantitative differences. The increase of glucose-6-phosphatase and simultaneous reduction of endoplasmic reticulum-membranes is illustrated by the dynamic structure of endoplasmic reticulum-membranes, which adapt to metabolic changes. The variable turnover of different parts of endoplasmic reticulum-membranes seems to be very important.", "contents": "[The fructose induces \"glycogenosis\". III. Histochemical and morphometrical studies of glycogen metabolism in mouse liver after fructose overload (author's transl)]. After feeding fructose for 7 days rat liver cells show an accumulation of glycogen, a high activity of glucose-6-phosphatase combined with a SER- and RER-reduction. This result was reviewed by mouse liver cells using histochemical and morphometrical methods. 60% fructose in drinking water was given mice as only nutritional source. Controls had free access to Altromin-R-standard diet and drinking water. Glycogen and glycogen metabolizing enzymes are demonstrated in the course of an 1-14 days fructose diet. After a 7 days diet liver tissue was analysed morphometrically. Feeding of fructose leads to a high glycogen content, combined with a high activity of glycogen-phosphorylase and glucose-6-phosphatase in the liver parenchyma of mouse. Glycogen-synthetase activity falls to a low level. The SER and RER and the peroxisomes are reduced. The single volume of the hepatic nucleus is decreased and the hepatocellular chondrioma is transformed in a smaller number of larger mitochondria. Compared with the rate the analysed organelles and enzymes of mouse liver show only slight quantitative differences. The increase of glucose-6-phosphatase and simultaneous reduction of endoplasmic reticulum-membranes is illustrated by the dynamic structure of endoplasmic reticulum-membranes, which adapt to metabolic changes. The variable turnover of different parts of endoplasmic reticulum-membranes seems to be very important."}
{"id": "PMID:200218", "title": "Cytochrome c oxidase activity in T/t6 (balanced lethal) mutant mice.", "content": "R-1 (1450g) and R-2 (25,000g) liver fractions from T/t6 and B6CBAF1 hybrid mice were analyzed for their protein content, mitochondria concentrations, and activities of three respiratory-chain enzymes of the mitochondrial inner membrane: cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase, E.C. 1.9.3.1.), alpha-glycerophosphate dehydrogenase [L-glycerol-3-phosphate: (acceptor) oxidoreductase, E.C. 1.1.99.5], and succinate-cytochrome c reductase. Only cytochrome c oxidase activity, calculated as units per 10(10) mitochondria, was significantly lower in both R-1 and R-2 fractions of T/t6 mice. Cytochrome c oxidase activity varied greatly among T/t6 mice, as did their liver mitochondria concentrations and body weights. Cytochrome c oxidase activity in the R-1 fraction of T/t6 mice, averaged about 40% lower than in B6CBAF1 mice. alpha-Glycerophosphate dehydrogenase activity was often elevated in T/t6 mice, particularly in the R-2 fraction. The T/t locus, a complex genetic locus on chromosome 17, may contain genes important to the function and biogenesis of mitochondria.", "contents": "Cytochrome c oxidase activity in T/t6 (balanced lethal) mutant mice. R-1 (1450g) and R-2 (25,000g) liver fractions from T/t6 and B6CBAF1 hybrid mice were analyzed for their protein content, mitochondria concentrations, and activities of three respiratory-chain enzymes of the mitochondrial inner membrane: cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase, E.C. 1.9.3.1.), alpha-glycerophosphate dehydrogenase [L-glycerol-3-phosphate: (acceptor) oxidoreductase, E.C. 1.1.99.5], and succinate-cytochrome c reductase. Only cytochrome c oxidase activity, calculated as units per 10(10) mitochondria, was significantly lower in both R-1 and R-2 fractions of T/t6 mice. Cytochrome c oxidase activity varied greatly among T/t6 mice, as did their liver mitochondria concentrations and body weights. Cytochrome c oxidase activity in the R-1 fraction of T/t6 mice, averaged about 40% lower than in B6CBAF1 mice. alpha-Glycerophosphate dehydrogenase activity was often elevated in T/t6 mice, particularly in the R-2 fraction. The T/t locus, a complex genetic locus on chromosome 17, may contain genes important to the function and biogenesis of mitochondria."}
{"id": "PMID:200219", "title": "The gross architecture of an antibody-combining site as determined by spin-label mapping.", "content": "1. A series of Dnp (dinitrophenyl) nitroxide spin labels was used to map the dimensions of the combining site of the Dnp-binding immunoglobulin A myeloma protein MOPC 315. The method compares the observed e.s.r. (electron-spin-resonance) hyperfine splittings with those calculated on the basis of different postulated motions for the spin label. The analysis is complicated by the sensitivity of the e.s.r. hyperfine splitting to the overall ;tumbling' time of the antibody-hapten complex and the polarity of the spin-label's environment. When these effects are considered quantitatively, it is then possible to determine the degree of mobility of each hapten which is allowed by the shape of the combining site. 2. The dinitrophenyl ring is rigidly held, and the depth of the site is 1.1-1.2nm and has lateral dimensions at the entrance to the site >/=0.6nmx0.9nm. The analysis of the results for spin-labelled haptens with chiral centres allows these lateral dimensions to be refined to 0.8nm and 1.1nm, and it is shown that the site is asymmetric with respect to the plane of the dinitrophenyl ring. 3. A polarity profile of the combining site was also obtained and a positively charged amino acid residue, possibly arginine-95(L) (light chain), was located at the entrance to the site. 4. The binding of Gd(III) to the antibody-hapten complexes results in quenching of the e.s.r. signal of the nitroxide. By using La(III) as a control, the paramagnetic contribution to the quenching is measured. 5. Analysis of the differential quenchings of the enantiomers of two five-membered nitroxide ring spin labels gives two possible locations of the metal-binding site. One of these is equidistant (0.7nm) from each of the three dinitrophenyl aromatic protons, and nuclear-magnetic-resonance relaxation studies, at 270MHz, on solutions of dinitrobenzene, Gd(III) and the Fv fragment (variable region of heavy and light chain) from protein MOPC 315 support this location for the metal site. 6. The e.s.r. and metal-binding data were then compared with the results of a model of the combining site constructed on the basis of framework invariance in immunoglobulins [Padlan, Davies, Pecht, Givol & Wright (1976) Cold Spring Harbor Symp. Quant. Biol.41, in the press]. The overall agreement is very good. Assignments of possible chelating groups for the metal can be made.", "contents": "The gross architecture of an antibody-combining site as determined by spin-label mapping. 1. A series of Dnp (dinitrophenyl) nitroxide spin labels was used to map the dimensions of the combining site of the Dnp-binding immunoglobulin A myeloma protein MOPC 315. The method compares the observed e.s.r. (electron-spin-resonance) hyperfine splittings with those calculated on the basis of different postulated motions for the spin label. The analysis is complicated by the sensitivity of the e.s.r. hyperfine splitting to the overall ;tumbling' time of the antibody-hapten complex and the polarity of the spin-label's environment. When these effects are considered quantitatively, it is then possible to determine the degree of mobility of each hapten which is allowed by the shape of the combining site. 2. The dinitrophenyl ring is rigidly held, and the depth of the site is 1.1-1.2nm and has lateral dimensions at the entrance to the site >/=0.6nmx0.9nm. The analysis of the results for spin-labelled haptens with chiral centres allows these lateral dimensions to be refined to 0.8nm and 1.1nm, and it is shown that the site is asymmetric with respect to the plane of the dinitrophenyl ring. 3. A polarity profile of the combining site was also obtained and a positively charged amino acid residue, possibly arginine-95(L) (light chain), was located at the entrance to the site. 4. The binding of Gd(III) to the antibody-hapten complexes results in quenching of the e.s.r. signal of the nitroxide. By using La(III) as a control, the paramagnetic contribution to the quenching is measured. 5. Analysis of the differential quenchings of the enantiomers of two five-membered nitroxide ring spin labels gives two possible locations of the metal-binding site. One of these is equidistant (0.7nm) from each of the three dinitrophenyl aromatic protons, and nuclear-magnetic-resonance relaxation studies, at 270MHz, on solutions of dinitrobenzene, Gd(III) and the Fv fragment (variable region of heavy and light chain) from protein MOPC 315 support this location for the metal site. 6. The e.s.r. and metal-binding data were then compared with the results of a model of the combining site constructed on the basis of framework invariance in immunoglobulins [Padlan, Davies, Pecht, Givol & Wright (1976) Cold Spring Harbor Symp. Quant. Biol.41, in the press]. The overall agreement is very good. Assignments of possible chelating groups for the metal can be made."}
{"id": "PMID:200220", "title": "Comparison of the dimensions of the combining sites of the dinitrophenyl-binding immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 by spin-label mapping.", "content": "The mouse immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 all possess dinitrophenyl (Dnp)-binding activity. Differences in specificities were shown by measuring the affinities of a variety of haptens. By using a series of Dnp-spin-labelled haptens, the dimensions of the binding sites of the three myeloma proteins were compared by the method described for protein MOPC 315 [Sutton, Gettins, Givol, Marsh, Wain-Hobson, Willan & Dwek (1977) Biochem. J.165, 177-197]. The dinitrophenyl ring is rigidly held in all three sites. The depths of the sites are all 1.1-1.2nm, but there are differences in the lateral dimensions at the entrance to the sites. For protein XRPC 25 these dimensions are 0.75nmx0.8nm, which may be compared with 0.85nmx1.1nm for protein MOPC 315 and >/=1.0nmx1.1nm for protein MOPC 460. The site in protein MOPC 460 is more symmetrical with respect to the plane of the dinitrophenyl ring than in either of the other two myeloma proteins and also allows greater penetration of solvent. In protein XRPC 25 a positively charged residue was located at the entrance to the site, similarly positioned to that reported for protein MOPC 315 [Sutton, Gettins, Givol, Marsh, Wain-Hobson, Willan & Dwek (1977) Biochem.J.165, 177-197]. All three proteins possess lanthanide-binding sites, but only in protein MOPC 315 is there antagonism between lanthanide and hapten binding. However, the effects of the diamagnetic La(III) on the electron-spin-resonance spectra of bound Dnp spin labels in both proteins MOPC 460 and XRPC 25 suggest an interaction between the two sites. Comparison of this effect with that caused by the addition of the paramagnetic Gd(III) enables the distance between the lanthanide- and hapten-binding sites to be calculated. In both proteins MOPC 460 and MOPC 315 the metal site is approx. 1.0nm from the nitroxide moiety of the spin-labelled hapten, but in protein XRPC 25 this distance is at least 2.0nm.", "contents": "Comparison of the dimensions of the combining sites of the dinitrophenyl-binding immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 by spin-label mapping. The mouse immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 all possess dinitrophenyl (Dnp)-binding activity. Differences in specificities were shown by measuring the affinities of a variety of haptens. By using a series of Dnp-spin-labelled haptens, the dimensions of the binding sites of the three myeloma proteins were compared by the method described for protein MOPC 315 [Sutton, Gettins, Givol, Marsh, Wain-Hobson, Willan & Dwek (1977) Biochem. J.165, 177-197]. The dinitrophenyl ring is rigidly held in all three sites. The depths of the sites are all 1.1-1.2nm, but there are differences in the lateral dimensions at the entrance to the sites. For protein XRPC 25 these dimensions are 0.75nmx0.8nm, which may be compared with 0.85nmx1.1nm for protein MOPC 315 and >/=1.0nmx1.1nm for protein MOPC 460. The site in protein MOPC 460 is more symmetrical with respect to the plane of the dinitrophenyl ring than in either of the other two myeloma proteins and also allows greater penetration of solvent. In protein XRPC 25 a positively charged residue was located at the entrance to the site, similarly positioned to that reported for protein MOPC 315 [Sutton, Gettins, Givol, Marsh, Wain-Hobson, Willan & Dwek (1977) Biochem.J.165, 177-197]. All three proteins possess lanthanide-binding sites, but only in protein MOPC 315 is there antagonism between lanthanide and hapten binding. However, the effects of the diamagnetic La(III) on the electron-spin-resonance spectra of bound Dnp spin labels in both proteins MOPC 460 and XRPC 25 suggest an interaction between the two sites. Comparison of this effect with that caused by the addition of the paramagnetic Gd(III) enables the distance between the lanthanide- and hapten-binding sites to be calculated. In both proteins MOPC 460 and MOPC 315 the metal site is approx. 1.0nm from the nitroxide moiety of the spin-labelled hapten, but in protein XRPC 25 this distance is at least 2.0nm."}
{"id": "PMID:200221", "title": "Variable-temperature magnetic-circular-dichroism spectra of cytochrome c oxidase and its derivatives.", "content": "A detailed study of the effect of temperature on the m.c.d. (magnetic circular dichroism) spectra of cytochrome c oxidase and some of its derivatives was undertaken to characterize the spin states of haem a and a(3). The fully reduced enzyme contains haem a(3) (2+) in its high-spin form and haem a(2+) in the low-spin state. This conclusion is reached by comparing the spectrum with that of the mixed-valence CO derivatives and its photolysis product. The cyanide derivative of the fully reduced enzyme contains both haem a and a(3) in the low-spin ferrous form. The m.c.d. spectra of the fully oxidized derivatives are consistent with the presence of one low-spin ferric haem group, assigned to a, which remains unaltered in the presence of ligands. Haem a(3) is high spin in the resting enzyme and the fluoride derivatives, and low spin in the cyanide form. The partially reduced formate and cyanide derivatives have temperature-dependent m.c.d. spectra due to the presence of high- and low-spin haem a(3) (3+) respectively. Haem a is low-spin ferrous in both. A comparison of the magnitude of the temperature-dependence of haem a(3) (3+) in the fully oxidized and partially reduced forms shows a marked difference which is tentatively ascribed to the presence of anti-ferromagnetic coupling in the fully oxidized form of the enzyme, and to its absence from the partially reduced derivatives, owing to the reduction of both Cu(2+) ions.", "contents": "Variable-temperature magnetic-circular-dichroism spectra of cytochrome c oxidase and its derivatives. A detailed study of the effect of temperature on the m.c.d. (magnetic circular dichroism) spectra of cytochrome c oxidase and some of its derivatives was undertaken to characterize the spin states of haem a and a(3). The fully reduced enzyme contains haem a(3) (2+) in its high-spin form and haem a(2+) in the low-spin state. This conclusion is reached by comparing the spectrum with that of the mixed-valence CO derivatives and its photolysis product. The cyanide derivative of the fully reduced enzyme contains both haem a and a(3) in the low-spin ferrous form. The m.c.d. spectra of the fully oxidized derivatives are consistent with the presence of one low-spin ferric haem group, assigned to a, which remains unaltered in the presence of ligands. Haem a(3) is high spin in the resting enzyme and the fluoride derivatives, and low spin in the cyanide form. The partially reduced formate and cyanide derivatives have temperature-dependent m.c.d. spectra due to the presence of high- and low-spin haem a(3) (3+) respectively. Haem a is low-spin ferrous in both. A comparison of the magnitude of the temperature-dependence of haem a(3) (3+) in the fully oxidized and partially reduced forms shows a marked difference which is tentatively ascribed to the presence of anti-ferromagnetic coupling in the fully oxidized form of the enzyme, and to its absence from the partially reduced derivatives, owing to the reduction of both Cu(2+) ions."}
{"id": "PMID:200222", "title": "Aldolase-like imine formation in the mechanism of action of phosphonoacetaldehyde hydrolase.", "content": "Phosphonoacetaldehyde hydrolase (EC 3.11.1.1), the bacterial enzyme that catalyses the reaction HCO-CH2-PO(OH)2+H2O leads to HCO-CH3+Pi, is inactivated by borohydride if either phosphonoacetaldehyde or acetaldehyde is present. This supports the suggestion that the substrate forms an imine with an amino group of the enzyme. Such imine formation would labilize the C-P bond in the same way that aldolase and related enzymes labilize C-C and C-H bonds (Scheme 1a).", "contents": "Aldolase-like imine formation in the mechanism of action of phosphonoacetaldehyde hydrolase. Phosphonoacetaldehyde hydrolase (EC 3.11.1.1), the bacterial enzyme that catalyses the reaction HCO-CH2-PO(OH)2+H2O leads to HCO-CH3+Pi, is inactivated by borohydride if either phosphonoacetaldehyde or acetaldehyde is present. This supports the suggestion that the substrate forms an imine with an amino group of the enzyme. Such imine formation would labilize the C-P bond in the same way that aldolase and related enzymes labilize C-C and C-H bonds (Scheme 1a)."}
{"id": "PMID:200223", "title": "Chromous ion reduction of mammalian cytochrome oxidase and some of its derivatives.", "content": "The reduction of cytochrome c oxidase by Cr2+, followed by means of stopped-flow spectrophotometry, exhibits two phases: the faster Cr2+-concentration-dependent reaction has an initial rate constant of 1.1 X 10(4)M-1-S-1, but reaches a rate limit at high concentration of reductant; the slower phase is concentration-independent with a rate of 0.3S-1. The activation energies of the fast and the slow processes are 35 and 71 kJ/mol respectively. The reduction kinetics of the mixed-valence CO complex and the cyanide-inhibited enzyme were compared with those of the fully oxidized forms: both the liganded species have a fast phase identical with that found in the oxidized oxidase. A comparison of the kinetic difference spectra obtained for the fast phase of reduction of oxidized oxidase with those obtained on reduction of the liganded species suggests that the rapid phase arises from the reduction ofhaem a, and the slow phase from the reduction of haem a3.", "contents": "Chromous ion reduction of mammalian cytochrome oxidase and some of its derivatives. The reduction of cytochrome c oxidase by Cr2+, followed by means of stopped-flow spectrophotometry, exhibits two phases: the faster Cr2+-concentration-dependent reaction has an initial rate constant of 1.1 X 10(4)M-1-S-1, but reaches a rate limit at high concentration of reductant; the slower phase is concentration-independent with a rate of 0.3S-1. The activation energies of the fast and the slow processes are 35 and 71 kJ/mol respectively. The reduction kinetics of the mixed-valence CO complex and the cyanide-inhibited enzyme were compared with those of the fully oxidized forms: both the liganded species have a fast phase identical with that found in the oxidized oxidase. A comparison of the kinetic difference spectra obtained for the fast phase of reduction of oxidized oxidase with those obtained on reduction of the liganded species suggests that the rapid phase arises from the reduction ofhaem a, and the slow phase from the reduction of haem a3."}
{"id": "PMID:200224", "title": "The effects of amphiphilic cationic drugs and inorganic cations on the activity of phosphatidate phosphohydrolase.", "content": "1. Phosphatidate phosphohydrolase from the particle-free supernatant of rat liver was assayed by using emulsions of phosphatidate as substrate. 2. The inhibition of the phosphohydrolase by chlorpromazine was of a competitive type with respect to phosphatidate. The potency of various amphiphilic cationic drugs as inhibitors of this reaction was related to their partition coefficients into a phosphatidate emulsion. 3. The effect of chlorpromazine on the phosphohydrolase activity was complementary rather than antagonistic towards Mg2+. Chlorpromazine stimulated the phosphohydrolase activity in the absence of added Mg2+ and was able to replace the requirement for Mg2+. However, at optimum concentrations of Mg2+, chlorpromazine inhibited the reaction, as did Ca2+. The phosphohydrolase activity was also stimulated by Co2+ and to a lesser extent by Mn2+, Fe2+, Fe3+, Ca2+, spermine and spermidine when Mg2+ was not added to the assays. 4. It is concluded that the inhibition of phosphatidate phosphohydrolase by amphiphilic cations can largely be explained by the interaction of these compounds with phosphatidate, which changes the physical properties of the lipid, making it less available for conversion into diacylglycerol. 5. The implications of these results to the effects of amphiphilic cations in redirecting glycerolipid synthesis at the level of phosphatidate are discussed.", "contents": "The effects of amphiphilic cationic drugs and inorganic cations on the activity of phosphatidate phosphohydrolase. 1. Phosphatidate phosphohydrolase from the particle-free supernatant of rat liver was assayed by using emulsions of phosphatidate as substrate. 2. The inhibition of the phosphohydrolase by chlorpromazine was of a competitive type with respect to phosphatidate. The potency of various amphiphilic cationic drugs as inhibitors of this reaction was related to their partition coefficients into a phosphatidate emulsion. 3. The effect of chlorpromazine on the phosphohydrolase activity was complementary rather than antagonistic towards Mg2+. Chlorpromazine stimulated the phosphohydrolase activity in the absence of added Mg2+ and was able to replace the requirement for Mg2+. However, at optimum concentrations of Mg2+, chlorpromazine inhibited the reaction, as did Ca2+. The phosphohydrolase activity was also stimulated by Co2+ and to a lesser extent by Mn2+, Fe2+, Fe3+, Ca2+, spermine and spermidine when Mg2+ was not added to the assays. 4. It is concluded that the inhibition of phosphatidate phosphohydrolase by amphiphilic cations can largely be explained by the interaction of these compounds with phosphatidate, which changes the physical properties of the lipid, making it less available for conversion into diacylglycerol. 5. The implications of these results to the effects of amphiphilic cations in redirecting glycerolipid synthesis at the level of phosphatidate are discussed."}
{"id": "PMID:200225", "title": "The isolation and characterization of corticotropin from the pituitary gland of the ostrich Struthio camelus.", "content": "1. Avian corticotropin (ACTH) was purified from both fresh and aged pituitary glands of the ostrich Struthio camelus. 2. The isolation of corticotropin in pure form involved acid/acetone extraction, NaCl fractionation, CM-cellulose chromatography and Sephadex G-50 chromatography. 3. The hormone preparations from fresh and aged glands behaved as single substances on polyacrylamide-gel electrophoresis, and both preparations were found to consist of 39 amino acid residues, in identical molar proportions for the different amino acids. 4. The isoelectric points of the two hormone preparations were estimated to be in the range pH 8.3-8.7, indicating possible differences in amide content, and the N-terminal amino acid of both preparations appeared to be serine. 5. The hormone preparations from fresh and aged glands exhibited similar biological potencies (73 and 77 i.u./mg respectively), as measured by steroidogenesis in vitro. 6. Apart from possible differences in amide content, the corticotropin preparations obtained from fresh and aged glands appear to be indistinguishable.", "contents": "The isolation and characterization of corticotropin from the pituitary gland of the ostrich Struthio camelus. 1. Avian corticotropin (ACTH) was purified from both fresh and aged pituitary glands of the ostrich Struthio camelus. 2. The isolation of corticotropin in pure form involved acid/acetone extraction, NaCl fractionation, CM-cellulose chromatography and Sephadex G-50 chromatography. 3. The hormone preparations from fresh and aged glands behaved as single substances on polyacrylamide-gel electrophoresis, and both preparations were found to consist of 39 amino acid residues, in identical molar proportions for the different amino acids. 4. The isoelectric points of the two hormone preparations were estimated to be in the range pH 8.3-8.7, indicating possible differences in amide content, and the N-terminal amino acid of both preparations appeared to be serine. 5. The hormone preparations from fresh and aged glands exhibited similar biological potencies (73 and 77 i.u./mg respectively), as measured by steroidogenesis in vitro. 6. Apart from possible differences in amide content, the corticotropin preparations obtained from fresh and aged glands appear to be indistinguishable."}
{"id": "PMID:200226", "title": "Binding proteins for adenosine 3':5'-cyclic monophosphate in bovine adrenal cortex.", "content": "Five peaks of cyclic AMP-binding activity could be resolved by DEAE-cellulose chromatography of bovine adrenal-cortex cytosol. Two of the binding peaks co-chromatographed with the catalytic activities of cyclic AMP-dependent protein kinases (ATP-protein phosphotransferase, EC 2.7.1.37) of type I or type II respectively. A third binding protein was eluted between the two kinases, and appeared to be the free regulatory moiety of protein kinase I. Two of the binding proteins for cyclic AMP, sedimenting at 9S in sucrose gradients, could also bind adenosine. They bound cyclic AMP with an apparent equilibrium dissociation constant (K(d)) of about 0.1mum, and showed an increased binding capacity for cyclic AMP after preincubation in the presence of K(+), Mg(2+) and ATP. The two binding proteins differed in their apparent affinities for adenosine. The isolated regulatory moiety of protein kinase I had a very high affinity for cyclic AMP (K(d)<0.1nm). At low ionic strength or in the presence of MgATP, the high-affinity binding of cyclic AMP to the regulatory subunit of protein kinase I was decreased by the catalytic subunit. At high ionic strength and in the absence of MgATP the high-affinity binding to the regulatory subunit was not affected by the presence of catalytic subunit. Under all experimental conditions tested, dissociation of protein kinase I was accompanied by an increased affinity for cyclic AMP. To gain some insight into the mechanism by which cyclic AMP activates protein kinase, the interaction between basic proteins, salt and the cyclic nucleotide in activating the kinase was studied.", "contents": "Binding proteins for adenosine 3':5'-cyclic monophosphate in bovine adrenal cortex. Five peaks of cyclic AMP-binding activity could be resolved by DEAE-cellulose chromatography of bovine adrenal-cortex cytosol. Two of the binding peaks co-chromatographed with the catalytic activities of cyclic AMP-dependent protein kinases (ATP-protein phosphotransferase, EC 2.7.1.37) of type I or type II respectively. A third binding protein was eluted between the two kinases, and appeared to be the free regulatory moiety of protein kinase I. Two of the binding proteins for cyclic AMP, sedimenting at 9S in sucrose gradients, could also bind adenosine. They bound cyclic AMP with an apparent equilibrium dissociation constant (K(d)) of about 0.1mum, and showed an increased binding capacity for cyclic AMP after preincubation in the presence of K(+), Mg(2+) and ATP. The two binding proteins differed in their apparent affinities for adenosine. The isolated regulatory moiety of protein kinase I had a very high affinity for cyclic AMP (K(d)<0.1nm). At low ionic strength or in the presence of MgATP, the high-affinity binding of cyclic AMP to the regulatory subunit of protein kinase I was decreased by the catalytic subunit. At high ionic strength and in the absence of MgATP the high-affinity binding to the regulatory subunit was not affected by the presence of catalytic subunit. Under all experimental conditions tested, dissociation of protein kinase I was accompanied by an increased affinity for cyclic AMP. To gain some insight into the mechanism by which cyclic AMP activates protein kinase, the interaction between basic proteins, salt and the cyclic nucleotide in activating the kinase was studied."}
{"id": "PMID:200248", "title": "Biological properties and clinical application of propolis. V. The action of ethanol extract of propolis (EEP) on laboratory animals. Histochemical investigations.", "content": "In the experiment on rats the ethanol extract of propolis (EEP) injections caused an activation of all experimental enzymes. The greatest effect EEP exerted was on NADPH2 tetrazolium reductase and glucose-6-phosphatase.", "contents": "Biological properties and clinical application of propolis. V. The action of ethanol extract of propolis (EEP) on laboratory animals. Histochemical investigations. In the experiment on rats the ethanol extract of propolis (EEP) injections caused an activation of all experimental enzymes. The greatest effect EEP exerted was on NADPH2 tetrazolium reductase and glucose-6-phosphatase."}
{"id": "PMID:200249", "title": "Effect of lithium on cyclic 3',5'-adenosine monophosphate formation in brain slices and its influence on phosphodiesterase.", "content": "The effect of lithium on cyclic 3',5'-adenosine monophosphate formation from precursor [8-14C]-adenine in guinea pig and rat brain slices and its influence on cAMP phosphodieesterase activity were studied. It was demonstrated that lithium stimulated cAMP formation in brain slices in correlation to its concentration. In guinea pig brain slices it stimulated cAMP formation in the presence of neurotransmitters and a phosphodiesterase inhibitor (histamine less than norepinephrine less than 5-OH-tryptamine). In rat brain slices, norepinephrine was also more effective than histamine. Phosphodiesterase inhibition was demonstrated only in preparations in which Triton X 100 was used.", "contents": "Effect of lithium on cyclic 3',5'-adenosine monophosphate formation in brain slices and its influence on phosphodiesterase. The effect of lithium on cyclic 3',5'-adenosine monophosphate formation from precursor [8-14C]-adenine in guinea pig and rat brain slices and its influence on cAMP phosphodieesterase activity were studied. It was demonstrated that lithium stimulated cAMP formation in brain slices in correlation to its concentration. In guinea pig brain slices it stimulated cAMP formation in the presence of neurotransmitters and a phosphodiesterase inhibitor (histamine less than norepinephrine less than 5-OH-tryptamine). In rat brain slices, norepinephrine was also more effective than histamine. Phosphodiesterase inhibition was demonstrated only in preparations in which Triton X 100 was used."}
{"id": "PMID:200250", "title": "[Receptor occupation and pharmacological activity as demonstrated on opiates (author's transl)].", "content": "The availability of highly radioactively labelled opiates with high receptor affinity has made it possible to identify and characterize opiate receptors in vitro as well as in vivo. These investigations revealed that the affinity of the compounds to the receptor decides about the pharmacological potency of the compounds. The differing action of opiate agonists and antagonists are explained by an allosteric receptor model. In vivo experiments showed that the dose range at which opiates induce specific pharmacological actions is identical with those doses at which increasing and finally complete receptor occupancy is obtained. Toxicological aspects of receptor occupation are discussed.", "contents": "[Receptor occupation and pharmacological activity as demonstrated on opiates (author's transl)]. The availability of highly radioactively labelled opiates with high receptor affinity has made it possible to identify and characterize opiate receptors in vitro as well as in vivo. These investigations revealed that the affinity of the compounds to the receptor decides about the pharmacological potency of the compounds. The differing action of opiate agonists and antagonists are explained by an allosteric receptor model. In vivo experiments showed that the dose range at which opiates induce specific pharmacological actions is identical with those doses at which increasing and finally complete receptor occupancy is obtained. Toxicological aspects of receptor occupation are discussed."}
{"id": "PMID:200247", "title": "Adjuvant polyarthritis. III. Evidence in support of viral etiology.", "content": "Intraperitoneal administration of a relatively small volume (0.2 ml) of plasma obtained from Sindbis virus--infected animals containing approximately 480 units of interferon/ml effectively suppressed the development of adjuvant arthritis. Similarly, administration of interferon (624 units/rat/day, ip) prepared in vitro by exposing rat embryo fibroblast culture to poly I:C in the presence of cycloheximide also suppressed the development of adjuvant arthritis without affecting the humoral or the cell-mediated immune response. The findings provide circumstantial evidence to the speculation that a virus or a virus-like organism plays a role in the pathogenesis of this disease.", "contents": "Adjuvant polyarthritis. III. Evidence in support of viral etiology. Intraperitoneal administration of a relatively small volume (0.2 ml) of plasma obtained from Sindbis virus--infected animals containing approximately 480 units of interferon/ml effectively suppressed the development of adjuvant arthritis. Similarly, administration of interferon (624 units/rat/day, ip) prepared in vitro by exposing rat embryo fibroblast culture to poly I:C in the presence of cycloheximide also suppressed the development of adjuvant arthritis without affecting the humoral or the cell-mediated immune response. The findings provide circumstantial evidence to the speculation that a virus or a virus-like organism plays a role in the pathogenesis of this disease."}
{"id": "PMID:200253", "title": "Reproducibility of measurements of oestrogen-receptor concentration in breast cancer.", "content": "The reproducibility of measurements of oestrogen-receptor activity has been examined in multiple specimens from a rabbit uterus, a rat mammary tumour and human breast tumours. The relationship between receptor concentration and tumour histology has also been investigated in 11 large primary tumours. In the animal tissues, receptor measurements were relatively reproducible (coefficient of variance: wet wt. basis 16-17%, protein basis 16-21%) but in human breast tumours receptor activity varied considerably (c.v.: wet wt. basis, 22-125%; protein basis, 28-72%). In addition to these variations in receptor activity within tumours, there was a difference between tumours, as demonstrated by an analysis of variance (P less than 0.01). In the 11 primary breast cancers selected for study, the level of receptor activity was related to menopausal status and the tumour content of the specimen. We conclude that the receptor activity detected varies within a tumour and depends upon the tumour content of the biopsy specimen. Predictions based on precise quantitation of receptor concentrations may therefore necessitate replicate tumour sampling and correction for the fraction of non-tumour tissue in each sample.", "contents": "Reproducibility of measurements of oestrogen-receptor concentration in breast cancer. The reproducibility of measurements of oestrogen-receptor activity has been examined in multiple specimens from a rabbit uterus, a rat mammary tumour and human breast tumours. The relationship between receptor concentration and tumour histology has also been investigated in 11 large primary tumours. In the animal tissues, receptor measurements were relatively reproducible (coefficient of variance: wet wt. basis 16-17%, protein basis 16-21%) but in human breast tumours receptor activity varied considerably (c.v.: wet wt. basis, 22-125%; protein basis, 28-72%). In addition to these variations in receptor activity within tumours, there was a difference between tumours, as demonstrated by an analysis of variance (P less than 0.01). In the 11 primary breast cancers selected for study, the level of receptor activity was related to menopausal status and the tumour content of the specimen. We conclude that the receptor activity detected varies within a tumour and depends upon the tumour content of the biopsy specimen. Predictions based on precise quantitation of receptor concentrations may therefore necessitate replicate tumour sampling and correction for the fraction of non-tumour tissue in each sample."}
{"id": "PMID:200254", "title": "Electron spin resonance of caeruloplasmin and iron transferrin in blood of patients with various malignant diseases.", "content": "Electron spin resonance studies have been made of caeruloplasmin and iron transferrin levels in whole blood of healthy controls and patients with a variety of malignant conditions receiving various forms of treatment. A small difference was found in caeruloplasmin level between normal males and females, although normal females receiving contraceptive steroids had an elevated level. No difference was found in iron transferrin level. Various conditions increased the caeruloplasmin and some also decreased the iron transferrin level in patients with malignant disease. These included surgery and the approach of a terminal phase of disease. Once allowance for these factors was made, the remaining small differences in Cu and Fe between patients with either squamous cell carcinoma or breast cancer and controls appeared to have no clinical significance.", "contents": "Electron spin resonance of caeruloplasmin and iron transferrin in blood of patients with various malignant diseases. Electron spin resonance studies have been made of caeruloplasmin and iron transferrin levels in whole blood of healthy controls and patients with a variety of malignant conditions receiving various forms of treatment. A small difference was found in caeruloplasmin level between normal males and females, although normal females receiving contraceptive steroids had an elevated level. No difference was found in iron transferrin level. Various conditions increased the caeruloplasmin and some also decreased the iron transferrin level in patients with malignant disease. These included surgery and the approach of a terminal phase of disease. Once allowance for these factors was made, the remaining small differences in Cu and Fe between patients with either squamous cell carcinoma or breast cancer and controls appeared to have no clinical significance."}
{"id": "PMID:200256", "title": "Effect of hormone replacement therapy on glucose tolerance in postmenopausal women.", "content": "Oral glucose tolerance tests were performed on 50 symptomatic postmenopausal women before and after three months of hormone replacement therapy. All patients were randomly allocated to one of five groups treated with various synthetic or so-called naturally occurring oestrogens. Therapy produced a significant deterioration of carbohydrate tolerance with sequential preparations containing 100 microgram of ethinyl oestradiol or graduated doses of mestranol up to 50 microgram. The conjugated equine oestrogen (1.25 mg daily) and oestrogen valerate (2 mg daily) treated groups did not show abnormal glucose tolerance. The decreased glucose tolerance may be due as much to dosage levels as to any metabolic characteristics of the various oestrogens prescribed.", "contents": "Effect of hormone replacement therapy on glucose tolerance in postmenopausal women. Oral glucose tolerance tests were performed on 50 symptomatic postmenopausal women before and after three months of hormone replacement therapy. All patients were randomly allocated to one of five groups treated with various synthetic or so-called naturally occurring oestrogens. Therapy produced a significant deterioration of carbohydrate tolerance with sequential preparations containing 100 microgram of ethinyl oestradiol or graduated doses of mestranol up to 50 microgram. The conjugated equine oestrogen (1.25 mg daily) and oestrogen valerate (2 mg daily) treated groups did not show abnormal glucose tolerance. The decreased glucose tolerance may be due as much to dosage levels as to any metabolic characteristics of the various oestrogens prescribed."}
{"id": "PMID:200260", "title": "Lipid binding by fragments of apolipoprotein C-III-1 obtained by thrombin cleavage.", "content": "We have used thrombin to cleave apolipoprotein C-III-1 into two fragments constituting residues 1-40 (apoLP-C-III-A) and 41-79 (apoLP-C-III-B). The lipid binding properties of these fragments with dimyristoyl- and 1-palmitoyl-2-oleoylphosphatidylcholines have been determined using circular dichroic and intrinsic tryptophan fluorescence spectroscopy. The peptide-phospholipid mixtures were fractionated by density gradients of cesium chloride. ApoLP-C-III-A showed disordered structure in the absence and presence of DMPC and no significant amount of peptide-phospholipid complex was isolated. ApoLP-C-III-B showed conformational changes in the circular dichroic spectrum and a shift in the intrinsic tryptophan fluorescence spectrum. Ultracentrifugation in cesium chloride gradients yielded peptide-phospholipid complexes isolated between density 1.10 and 1.18. The molar ratio of lipid to protein was 12:1. The results of these studies and the examination of space filling models of apoLP-C-III provide evidence that an amphipathic alpha helix which contains a nonpolar face and a polar face is the basic structural unit for binding of phospholipid by the plasma apolipoproteins. These results also provide direct evidence that the hydrophobicity of the nonpolar face is important in lipid binding since the nonpolar face of residues 1-40 is considerably less hydrophobic than the nonpolar face of residues 41-79.", "contents": "Lipid binding by fragments of apolipoprotein C-III-1 obtained by thrombin cleavage. We have used thrombin to cleave apolipoprotein C-III-1 into two fragments constituting residues 1-40 (apoLP-C-III-A) and 41-79 (apoLP-C-III-B). The lipid binding properties of these fragments with dimyristoyl- and 1-palmitoyl-2-oleoylphosphatidylcholines have been determined using circular dichroic and intrinsic tryptophan fluorescence spectroscopy. The peptide-phospholipid mixtures were fractionated by density gradients of cesium chloride. ApoLP-C-III-A showed disordered structure in the absence and presence of DMPC and no significant amount of peptide-phospholipid complex was isolated. ApoLP-C-III-B showed conformational changes in the circular dichroic spectrum and a shift in the intrinsic tryptophan fluorescence spectrum. Ultracentrifugation in cesium chloride gradients yielded peptide-phospholipid complexes isolated between density 1.10 and 1.18. The molar ratio of lipid to protein was 12:1. The results of these studies and the examination of space filling models of apoLP-C-III provide evidence that an amphipathic alpha helix which contains a nonpolar face and a polar face is the basic structural unit for binding of phospholipid by the plasma apolipoproteins. These results also provide direct evidence that the hydrophobicity of the nonpolar face is important in lipid binding since the nonpolar face of residues 1-40 is considerably less hydrophobic than the nonpolar face of residues 41-79."}
{"id": "PMID:200263", "title": "Angiotensin I converting enzyme from human plasma.", "content": "The angiotensin I converting enzyme was purified 101 000-fold to homogeneity from human plasma by a combination of chromatographic and electrophoretic techniques. The enzyme is similar to other angiotensin I converting enzymes. It is an acidic glycoprotein consisting of a single polypeptide chain of molecular weight 140 000 with an isoelectric point of 4.6. The enzyme requires chloride ion for activity and is inhibited by ethylenediaminetetraacetic acid, angiotensin II, bradykinin, bradykinin potentiating factor nonapeptide, and 3-mercapto-2-D-methylpropanoyl-L-proline (SQ-14,225). The purified preparation cleaves bradykinin as well as angiotensin II and hippuryl-L-histidyl-L-leucine. Its specific activity with angiotensin I is 2.4 units per mg and with hippuryl-L-histidyl-L-leucine is 31.4 units per mg.", "contents": "Angiotensin I converting enzyme from human plasma. The angiotensin I converting enzyme was purified 101 000-fold to homogeneity from human plasma by a combination of chromatographic and electrophoretic techniques. The enzyme is similar to other angiotensin I converting enzymes. It is an acidic glycoprotein consisting of a single polypeptide chain of molecular weight 140 000 with an isoelectric point of 4.6. The enzyme requires chloride ion for activity and is inhibited by ethylenediaminetetraacetic acid, angiotensin II, bradykinin, bradykinin potentiating factor nonapeptide, and 3-mercapto-2-D-methylpropanoyl-L-proline (SQ-14,225). The purified preparation cleaves bradykinin as well as angiotensin II and hippuryl-L-histidyl-L-leucine. Its specific activity with angiotensin I is 2.4 units per mg and with hippuryl-L-histidyl-L-leucine is 31.4 units per mg."}
{"id": "PMID:200265", "title": "Effect of coenzymes and temperature on the process of in vitro refolding and reassociation of lactic dehydrogenase isoenzymes.", "content": "Dissociation and deactivation of the H4 and M4 isoenzymes of lactic dehydrogenase in strong denaturants may be reversed with a yield of reactivation up to 100%. The products of reconstitution are indistinguishable from the native enzymes as far as the Michaelis constants and the dissociation constants for substrate and coenzyme as well as spectral and hydrodynamic properties are concerned. The presence of NAD+ and NADH does not affect either the conformational state of the product of reconstitution, or the kinetics of reactivation, using the pure apoenzymes as a reference. At 20 degrees C the kinetics of reactivation for LDH-M4 in the presence and absence of coenzyme may be quantitatively described by a second-order rate equation (k2 = 23.4 +/- 2.6 mM-1S-1) while LDH-H4 is characterized by a uni-bimolecular reaction sequence (k1 = 1.45 +/- 0.45 X 10(-3)-S-1, k2 = 5 +/- 1 mM-1S-1), in agreement with earlier observations (Rudolph, R., et al. (1977), Biochemistry 16, 3384-3390). Regarding the influence of temperature on the rate of reactivation no significant anomalies are detectable within the range of 0-25 degrees C. The (apparent) activation energies, taken from the linear Arrhenius plots, are 58 kcal/mol for the association reaction of LDH-M4, and 41 kcal/mol for the transconformation reaction of LDH-H4.", "contents": "Effect of coenzymes and temperature on the process of in vitro refolding and reassociation of lactic dehydrogenase isoenzymes. Dissociation and deactivation of the H4 and M4 isoenzymes of lactic dehydrogenase in strong denaturants may be reversed with a yield of reactivation up to 100%. The products of reconstitution are indistinguishable from the native enzymes as far as the Michaelis constants and the dissociation constants for substrate and coenzyme as well as spectral and hydrodynamic properties are concerned. The presence of NAD+ and NADH does not affect either the conformational state of the product of reconstitution, or the kinetics of reactivation, using the pure apoenzymes as a reference. At 20 degrees C the kinetics of reactivation for LDH-M4 in the presence and absence of coenzyme may be quantitatively described by a second-order rate equation (k2 = 23.4 +/- 2.6 mM-1S-1) while LDH-H4 is characterized by a uni-bimolecular reaction sequence (k1 = 1.45 +/- 0.45 X 10(-3)-S-1, k2 = 5 +/- 1 mM-1S-1), in agreement with earlier observations (Rudolph, R., et al. (1977), Biochemistry 16, 3384-3390). Regarding the influence of temperature on the rate of reactivation no significant anomalies are detectable within the range of 0-25 degrees C. The (apparent) activation energies, taken from the linear Arrhenius plots, are 58 kcal/mol for the association reaction of LDH-M4, and 41 kcal/mol for the transconformation reaction of LDH-H4."}
{"id": "PMID:200266", "title": "Mutations in Escherichia coli altering an apurinic endonuclease, endonuclease II, and exonuclease III and their effect on in vivo sensitivity to methylmethanesulfonate.", "content": "The levels of endonuclease II, an apurinic endonuclease, and exonuclease III in the parent strains (AB 1157) of Escherichia coli and in various mutants were determined by chromatography on DEAE-cellulose. AB 3027 and NH 5016 lacked endonuclease II and exonuclease III. BW 2001 lacked the apurinic endonuclease and exonuclease III while BW 2007, BW 9093, and BW 9059 lacked only exonuclease III. Deletion mutants BW 9101 and BW 9109 lacked all three enzymes. The latter mutants locate the genes for the two endonucleases in the region of exonuclease III (chith) of 38.2 min (White et al., 1976). All of the mutants which were sensitive to methylmethanesulfonate in vivo lacked exonuclease III, but not all mutants lacking exonuclease III were MMS sensitive. The deletion mutants and NH 5016 were the exceptions.", "contents": "Mutations in Escherichia coli altering an apurinic endonuclease, endonuclease II, and exonuclease III and their effect on in vivo sensitivity to methylmethanesulfonate. The levels of endonuclease II, an apurinic endonuclease, and exonuclease III in the parent strains (AB 1157) of Escherichia coli and in various mutants were determined by chromatography on DEAE-cellulose. AB 3027 and NH 5016 lacked endonuclease II and exonuclease III. BW 2001 lacked the apurinic endonuclease and exonuclease III while BW 2007, BW 9093, and BW 9059 lacked only exonuclease III. Deletion mutants BW 9101 and BW 9109 lacked all three enzymes. The latter mutants locate the genes for the two endonucleases in the region of exonuclease III (chith) of 38.2 min (White et al., 1976). All of the mutants which were sensitive to methylmethanesulfonate in vivo lacked exonuclease III, but not all mutants lacking exonuclease III were MMS sensitive. The deletion mutants and NH 5016 were the exceptions."}
{"id": "PMID:200268", "title": "Purification and characterization of baboon endogenous virus DNA polymerase.", "content": "An RNA-directed DNA polymerase was purified from baboon endogenous type-C virus by successive column chromatography on DEAE cellulose, phosphocellulose and hydroxyapatite. The purified DNA polymerase has a molecular weight of 68 000, a pH optimum of 8.0, a Mn2+ optimum of 1 mM, and a KCl optimum of 40 mM. The purified enzyme transcribes heteropolymeric regions of viral 60--70 S RNA isolated from different type-C viruses. The purified enzyme is immunologically related to a similarly purified polymerase from the cat endogenous type-C virus RD114.", "contents": "Purification and characterization of baboon endogenous virus DNA polymerase. An RNA-directed DNA polymerase was purified from baboon endogenous type-C virus by successive column chromatography on DEAE cellulose, phosphocellulose and hydroxyapatite. The purified DNA polymerase has a molecular weight of 68 000, a pH optimum of 8.0, a Mn2+ optimum of 1 mM, and a KCl optimum of 40 mM. The purified enzyme transcribes heteropolymeric regions of viral 60--70 S RNA isolated from different type-C viruses. The purified enzyme is immunologically related to a similarly purified polymerase from the cat endogenous type-C virus RD114."}
{"id": "PMID:200269", "title": "Conformational changes in yeast tRNATyr revealed by EPR spectra of spin-labelled N6-(delta2-isopentenyl)-adenosine residue.", "content": "Temperature-induced conformational changes in the anticodon region of yeast tRNATyr were studied by EPR spectroscopy. The spin label 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl was attached to the N6-(delta2-isopentenyl)-adenosine residue in tRNATyr, previously made reactive by iodination. The labelled tRNATyr gave an asymmetrical triplet spectrum typical of rapidly tumbling nitroxide, with a rotational correlation time (tauc) of 0.65 ns. Spin-labelled tRNATyr was exposed to heating and cooling in three different buffers each with or without MgCl2. In each case the Arrhenius plot of --log tauc vs. inverse absolute temperature gave two straight lines, intersecting at a critical temperature (tcr). Above tcr, the anisotropy of the spectrum was not reduced and the activation energy of motion increased, indicating that the transition is associated with a conformational change of the macromolecule. Transitions in 0.05 M potassium phosphate (pH 8.0) and 0.02 M Tris - HC1 (pH 7.0) were observed at potassium phosphate (pH 8.0) and 0.02 M Tris - Hc1 (pH 7.0) were observed at approx. 37 degrees C. When 0.01 M mgCl2 was present in these buffers, transitions were shifted to 46 degrees and 53 degrees C, respectively. Transitions in 0.01 M sodium cacodylate were observed at temperatures which are significantly lower. Since all these transitions occur at temperatures considerably below those required to melt the helical regions of tRNA, and at least approximately 10 degrees C below those reported to break tertiary interactions, it is supposed that they reflect some reorientation of the anticodon region, e.g. a change in tilt of the bases.", "contents": "Conformational changes in yeast tRNATyr revealed by EPR spectra of spin-labelled N6-(delta2-isopentenyl)-adenosine residue. Temperature-induced conformational changes in the anticodon region of yeast tRNATyr were studied by EPR spectroscopy. The spin label 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl was attached to the N6-(delta2-isopentenyl)-adenosine residue in tRNATyr, previously made reactive by iodination. The labelled tRNATyr gave an asymmetrical triplet spectrum typical of rapidly tumbling nitroxide, with a rotational correlation time (tauc) of 0.65 ns. Spin-labelled tRNATyr was exposed to heating and cooling in three different buffers each with or without MgCl2. In each case the Arrhenius plot of --log tauc vs. inverse absolute temperature gave two straight lines, intersecting at a critical temperature (tcr). Above tcr, the anisotropy of the spectrum was not reduced and the activation energy of motion increased, indicating that the transition is associated with a conformational change of the macromolecule. Transitions in 0.05 M potassium phosphate (pH 8.0) and 0.02 M Tris - HC1 (pH 7.0) were observed at potassium phosphate (pH 8.0) and 0.02 M Tris - Hc1 (pH 7.0) were observed at approx. 37 degrees C. When 0.01 M mgCl2 was present in these buffers, transitions were shifted to 46 degrees and 53 degrees C, respectively. Transitions in 0.01 M sodium cacodylate were observed at temperatures which are significantly lower. Since all these transitions occur at temperatures considerably below those required to melt the helical regions of tRNA, and at least approximately 10 degrees C below those reported to break tertiary interactions, it is supposed that they reflect some reorientation of the anticodon region, e.g. a change in tilt of the bases."}
{"id": "PMID:200270", "title": "Cytoplasmic and nuclear protein kinases during the cell cycle.", "content": "Nuclear and cytoplasmic protein kinases were measured during the traverse of synchronous CHO cultures through G1 into S phase. Cells were synchronized by selective detachment of cells blocked in metaphase using colcemid. Nuclei were isolated and the protein kinases extracted from the nuclear preparation with 0.6 M NaCl. This procedure solubilized greater than 90% of the total protein kinase activity present in the nuclear preparation. DEAE chromatography of this extract showed 5 apparently different ionic forms of nuclear protein kinases. The nuclear protein kinases preferred casein and phosvitin to histone as substrates and were cyclic AMP-independent. Nuclear protein kinase activities increased greater than two-fold, when expressed as units of activity per cell nucleus, during G1 phase traverse, concomitant with a 70% increase in nuclear non-histone proteins (those soluble in 0.6 M NaCl). This resulted in only a 40% increase in the specific activities (units/microgram protein in 0.6 M NaCl extractable nuclear fraction) of these enzymes as cells progressed through G1 into S phase. This was in contrast to cytoplasmic cyclic AMP-dependent protein kinase activities which also increased two-fold during progression through G1 phase while total cellular protein increased less than 20%. Activation of, as well as synthesis of, cyclic AMP-dependent cytoplasmic protein kinases during G1 phase suggests a regulatory mechanism for precise temporal phosphorylation, whereas the constant specific activity in nuclear kinases during cell cycle is more compatible with the maintenance of bulk phosphorylation processes in the nucleus.", "contents": "Cytoplasmic and nuclear protein kinases during the cell cycle. Nuclear and cytoplasmic protein kinases were measured during the traverse of synchronous CHO cultures through G1 into S phase. Cells were synchronized by selective detachment of cells blocked in metaphase using colcemid. Nuclei were isolated and the protein kinases extracted from the nuclear preparation with 0.6 M NaCl. This procedure solubilized greater than 90% of the total protein kinase activity present in the nuclear preparation. DEAE chromatography of this extract showed 5 apparently different ionic forms of nuclear protein kinases. The nuclear protein kinases preferred casein and phosvitin to histone as substrates and were cyclic AMP-independent. Nuclear protein kinase activities increased greater than two-fold, when expressed as units of activity per cell nucleus, during G1 phase traverse, concomitant with a 70% increase in nuclear non-histone proteins (those soluble in 0.6 M NaCl). This resulted in only a 40% increase in the specific activities (units/microgram protein in 0.6 M NaCl extractable nuclear fraction) of these enzymes as cells progressed through G1 into S phase. This was in contrast to cytoplasmic cyclic AMP-dependent protein kinase activities which also increased two-fold during progression through G1 phase while total cellular protein increased less than 20%. Activation of, as well as synthesis of, cyclic AMP-dependent cytoplasmic protein kinases during G1 phase suggests a regulatory mechanism for precise temporal phosphorylation, whereas the constant specific activity in nuclear kinases during cell cycle is more compatible with the maintenance of bulk phosphorylation processes in the nucleus."}
{"id": "PMID:200271", "title": "Myeloperoxidase inactivation in the course of catalysis of chlorination of taurine.", "content": "Myeloperoxidase (donor: hydrogen-peroxide oxidoreductase, EC 1.11.1.7) was isolated from leukocytes of patients with chronic granulocyte leukemia. In the presence of H2O2 and Cl- at pH 4.0-6.6 the myeloperoxidase catalyses chlorination of taurine to monochloramine taurine and simultaneously undergoes inactivation. The myeloperoxidase inactivation rate depends on the concentration of H2O2 and Cl-: both the initial rate of chlorination and myeloperoxidase inactivation rate increase with increasing concentration of H2O2. However, an increase in concentration of Cl- results in a decrease in enzyme inactivation. At a given H2O2 concentration, myeloperoxidase inactivation is a first order reaction, which implied that the enzyme may react with a substrate a limited number of times.", "contents": "Myeloperoxidase inactivation in the course of catalysis of chlorination of taurine. Myeloperoxidase (donor: hydrogen-peroxide oxidoreductase, EC 1.11.1.7) was isolated from leukocytes of patients with chronic granulocyte leukemia. In the presence of H2O2 and Cl- at pH 4.0-6.6 the myeloperoxidase catalyses chlorination of taurine to monochloramine taurine and simultaneously undergoes inactivation. The myeloperoxidase inactivation rate depends on the concentration of H2O2 and Cl-: both the initial rate of chlorination and myeloperoxidase inactivation rate increase with increasing concentration of H2O2. However, an increase in concentration of Cl- results in a decrease in enzyme inactivation. At a given H2O2 concentration, myeloperoxidase inactivation is a first order reaction, which implied that the enzyme may react with a substrate a limited number of times."}
{"id": "PMID:200272", "title": "Some properties of purified phosphoprotein phosphatases from rabbit liver.", "content": "The activity of two purified homogeneous phosphoprotein phosphatases types P I and P II) (phosphoprotein phosphohydrolase, EC 3.1.3.16) from rabbit liver (Khandelwal, R.L., Vandenheede, J.R., and Krebs, E.G. (1976) J. Biol. Chem. 251, 4850-4858) were examined in the presence of divalent cations, Pi, PPi, nucleotides, glycolytic intermediates and a number of other compounds using phosphorylase a, glycogen synthase D and phosphorylated histone as substrates. Enzyme activities were usually inhibited by divalent cations with all substrates; the inhibition being more pronounced with phosphorylase a. Zn2+ was the most potent inhibitor among the divalent cations tested. The enzyme was competitively inhibited by PPi (Ki = 0.1 mM for P I and 0.3 mM for PII), Pi (Ki = 15 mM for P I and 19.8 mM for P II) and p-nitrophenyl phosphate (Ki = 1 mM and 1.4 mM for P I and P II, respectively) employing phosphorylase a as the substrate. The compounds along with a number of others (Na2SO4, citrate, NaF and EDTA) also inhibited the enzyme activity with the other two substrates. Severe inhibition of the enzyme was also observed in the presence of the adenine and uridine nucleotides; monophosphate nucleotides being more inhibitory with phosphorylase a, whereas the di- and triphosphate nucleotides showed more inhibition with glycogen synthase D and phosphorylated histone. Cyclic AMP had no significant effect on enzyme activity with all the substrates tested. Phosphorylated metabolites did not show any marked effect on the enzyme activity with phosphorylase a as the substrate.", "contents": "Some properties of purified phosphoprotein phosphatases from rabbit liver. The activity of two purified homogeneous phosphoprotein phosphatases types P I and P II) (phosphoprotein phosphohydrolase, EC 3.1.3.16) from rabbit liver (Khandelwal, R.L., Vandenheede, J.R., and Krebs, E.G. (1976) J. Biol. Chem. 251, 4850-4858) were examined in the presence of divalent cations, Pi, PPi, nucleotides, glycolytic intermediates and a number of other compounds using phosphorylase a, glycogen synthase D and phosphorylated histone as substrates. Enzyme activities were usually inhibited by divalent cations with all substrates; the inhibition being more pronounced with phosphorylase a. Zn2+ was the most potent inhibitor among the divalent cations tested. The enzyme was competitively inhibited by PPi (Ki = 0.1 mM for P I and 0.3 mM for PII), Pi (Ki = 15 mM for P I and 19.8 mM for P II) and p-nitrophenyl phosphate (Ki = 1 mM and 1.4 mM for P I and P II, respectively) employing phosphorylase a as the substrate. The compounds along with a number of others (Na2SO4, citrate, NaF and EDTA) also inhibited the enzyme activity with the other two substrates. Severe inhibition of the enzyme was also observed in the presence of the adenine and uridine nucleotides; monophosphate nucleotides being more inhibitory with phosphorylase a, whereas the di- and triphosphate nucleotides showed more inhibition with glycogen synthase D and phosphorylated histone. Cyclic AMP had no significant effect on enzyme activity with all the substrates tested. Phosphorylated metabolites did not show any marked effect on the enzyme activity with phosphorylase a as the substrate."}
{"id": "PMID:200273", "title": "Thiol groups of Escherichia coli citrate synthase and their influence on activity and regulation.", "content": "The modification of Escherichia coli citrate synthase (citrate oxaloacetatelyase(pro-3S-CH2.COO- leads to acetyl-CoA, EC 4.1.3.7) with 5,5'-dithiobis-(2-nitrobenzoic acid) has been investigated. (1) In low ionic strength (20 mM Tris.HCl, pH 8.0): (A) Eight thiol groups per tetramer of the native enzyme reacted with Nbs2. (b) Two of the eight accessible thiols were modified rapidly with the loss of 26% enzyme activity but with no change in the NADH inhibition. The remaining six were modified more slowly, resulting in a further 60% loss of activity and complete densensitization to NADH. (c) The 2nd-order rate constant for the modification of the rapidly reacting thiols is 2.5.10(4) M-1.min-1. At the reagent concentrations used (0.1 to 0.2 mM) the modification of the six thiols in the slow kinetic set appeared to be 1st-order; at 0.1 mM dithionitrobenzoic acid their rate of modification was approximately 30 times slower than the thiols in the fast kinetic set. (2) In high ionic strength (20 mM Tris.HCl, pH 8.0, 0.1 M KCl): (a) Four thiol groups were modified in a single kinetic set and it appeared that these thiols are four of the six slowly modified in the absence of KCl. (b) The modification resulted in 70% loss of enzyme activity and complete loss of NADH inhibition. (3) From the kinetic analysis it is proposed that the four thiol groups accessible to dithionitrobenzoic acid in the absence and presence of 0.1 M KCl are those involved in the response of NADH. Modification of any one of these four groups produced no reduction in the inhibition; instead, loss of NADH sensitivity was coincident with the appearance of tetrameric protein possessing three substituted thiols, whereas enzyme with one or two modified groups was still fully inhibited by NADH.", "contents": "Thiol groups of Escherichia coli citrate synthase and their influence on activity and regulation. The modification of Escherichia coli citrate synthase (citrate oxaloacetatelyase(pro-3S-CH2.COO- leads to acetyl-CoA, EC 4.1.3.7) with 5,5'-dithiobis-(2-nitrobenzoic acid) has been investigated. (1) In low ionic strength (20 mM Tris.HCl, pH 8.0): (A) Eight thiol groups per tetramer of the native enzyme reacted with Nbs2. (b) Two of the eight accessible thiols were modified rapidly with the loss of 26% enzyme activity but with no change in the NADH inhibition. The remaining six were modified more slowly, resulting in a further 60% loss of activity and complete densensitization to NADH. (c) The 2nd-order rate constant for the modification of the rapidly reacting thiols is 2.5.10(4) M-1.min-1. At the reagent concentrations used (0.1 to 0.2 mM) the modification of the six thiols in the slow kinetic set appeared to be 1st-order; at 0.1 mM dithionitrobenzoic acid their rate of modification was approximately 30 times slower than the thiols in the fast kinetic set. (2) In high ionic strength (20 mM Tris.HCl, pH 8.0, 0.1 M KCl): (a) Four thiol groups were modified in a single kinetic set and it appeared that these thiols are four of the six slowly modified in the absence of KCl. (b) The modification resulted in 70% loss of enzyme activity and complete loss of NADH inhibition. (3) From the kinetic analysis it is proposed that the four thiol groups accessible to dithionitrobenzoic acid in the absence and presence of 0.1 M KCl are those involved in the response of NADH. Modification of any one of these four groups produced no reduction in the inhibition; instead, loss of NADH sensitivity was coincident with the appearance of tetrameric protein possessing three substituted thiols, whereas enzyme with one or two modified groups was still fully inhibited by NADH."}
{"id": "PMID:200274", "title": "Synthesis of phospholipids in mitochondria and other membrane fractions of rabbit reticulocytes.", "content": "1. Reticulocytosis of 40-50% was obtained in rabbits by daily bleeding. Reticulocytes (plus erythrocytes) were subfractionated into plasma membrane fraction, mitochondria and the post-mitochondrial fraction. 2. In all fractions, fatty acids were incorporated into phospholipids. This process was ATP dependent and represented acylation of lysophospholipids. 3. Incorporation of fatty acids into lysophosphatidic and phosphatidic acids occurred only in the presence of sn-glycerol 3-phosphate and was observed in mitochondria and the post-mitochondrial fraction. It represents a two-step acylation of sn-glycerol 3-phosphate. 4. Incorporation of phosphorylcholine from CDPcholine into phosphatidylcholine was observed in the mitochondrial and the post-mitochondrial fractions. This activity was correlated with NADPH-cytochrome c reductase and was probably connected with the remnants of the endoplasmic reticulum.", "contents": "Synthesis of phospholipids in mitochondria and other membrane fractions of rabbit reticulocytes. 1. Reticulocytosis of 40-50% was obtained in rabbits by daily bleeding. Reticulocytes (plus erythrocytes) were subfractionated into plasma membrane fraction, mitochondria and the post-mitochondrial fraction. 2. In all fractions, fatty acids were incorporated into phospholipids. This process was ATP dependent and represented acylation of lysophospholipids. 3. Incorporation of fatty acids into lysophosphatidic and phosphatidic acids occurred only in the presence of sn-glycerol 3-phosphate and was observed in mitochondria and the post-mitochondrial fraction. It represents a two-step acylation of sn-glycerol 3-phosphate. 4. Incorporation of phosphorylcholine from CDPcholine into phosphatidylcholine was observed in the mitochondrial and the post-mitochondrial fractions. This activity was correlated with NADPH-cytochrome c reductase and was probably connected with the remnants of the endoplasmic reticulum."}
{"id": "PMID:200275", "title": "Hydrolysis of phosphatidylcholine by phospholipase A2 does not cause dissociation of apolipoprotein C from rat plasma very low density lipoprotein.", "content": "To test the hypothesis that hydrolysis of glycerophosphatides causes displacement of apolipoprotein C from very low density lipoprotein, we have studied the effects of a snake venom phospholipase A2 on very low density lipoprotein labeled with [125I]apoC, [3H]cholesterol, [14C]palmitate and [32P]phospholipids. In spite of hydrolysis of 97% of the phosphatidylcholine, only small amounts of labeled apoC and labeled cholesterol were displaced from the very low density lipoprotein. With purified lipoprotein lipase in contrast, 80-90% of the labeled apoC and cholesterol were removed from the lipoprotein. It is concluded that hydrolysis of phosphatidylcholine does not cause an appreciable dissociation of apolipoprotein C from very low density lipoprotein.", "contents": "Hydrolysis of phosphatidylcholine by phospholipase A2 does not cause dissociation of apolipoprotein C from rat plasma very low density lipoprotein. To test the hypothesis that hydrolysis of glycerophosphatides causes displacement of apolipoprotein C from very low density lipoprotein, we have studied the effects of a snake venom phospholipase A2 on very low density lipoprotein labeled with [125I]apoC, [3H]cholesterol, [14C]palmitate and [32P]phospholipids. In spite of hydrolysis of 97% of the phosphatidylcholine, only small amounts of labeled apoC and labeled cholesterol were displaced from the very low density lipoprotein. With purified lipoprotein lipase in contrast, 80-90% of the labeled apoC and cholesterol were removed from the lipoprotein. It is concluded that hydrolysis of phosphatidylcholine does not cause an appreciable dissociation of apolipoprotein C from very low density lipoprotein."}
{"id": "PMID:200277", "title": "Studies on adenosine 3',5'-phosphate-binding and adenosine 3',5-phosphate-dependent protein kinase activities associated with subcellular fractions of Chinese hamster ovary cells.", "content": "Both cyclic AMP-binding and cyclic AMP-dependent protein kinase activities exist in Chinese hamster ovary cell extract. Competition experiments demonstrate that the binding is specific for cyclic AMP. All cellular elements including nucleus, mitochondria, plasma membrane, microsome, ribosome and cytosol contain both activities. Binding activity is highest in the cytosol and lowest in the nucleus. Each fraction contains endogenous protein kinase activity which is insensitive to cyclic AMP activation. When histone was used as a substrate, protein kinase activity in all fractions was stimulated by cyclic AMP (with the highest in cytosol and lowest in the nucleus) and inhibited by Walsh's protein kinase inhibitor.", "contents": "Studies on adenosine 3',5'-phosphate-binding and adenosine 3',5-phosphate-dependent protein kinase activities associated with subcellular fractions of Chinese hamster ovary cells. Both cyclic AMP-binding and cyclic AMP-dependent protein kinase activities exist in Chinese hamster ovary cell extract. Competition experiments demonstrate that the binding is specific for cyclic AMP. All cellular elements including nucleus, mitochondria, plasma membrane, microsome, ribosome and cytosol contain both activities. Binding activity is highest in the cytosol and lowest in the nucleus. Each fraction contains endogenous protein kinase activity which is insensitive to cyclic AMP activation. When histone was used as a substrate, protein kinase activity in all fractions was stimulated by cyclic AMP (with the highest in cytosol and lowest in the nucleus) and inhibited by Walsh's protein kinase inhibitor."}
{"id": "PMID:200278", "title": "Effects of isoproterenol on cyclic AMP and cyclic AMP-dependent protein kinase in developing chick myocardium.", "content": "Embryonic chick (7-9 day) and newborn chick myocardia contain one major peak of cyclic AMP-dependent protein kinase activity as assessed by DEAE-cellulose chromatography. Evidence is presented that the cyclic AMP-dependent protein kinase activity ratios (activity in absence of cyclic AMP/activity in presence of added cyclic AMP) of homogenates prepared with low ionic strength buffer reflect the endogenous activation state of the enzyme. The cyclic AMP content of newborn chick myocardium is lower than that of 7--9 day embryonic chick myocardium; the baseline cyclic AMP-dependent protein kinase activity is correspondingly reduced. Isoproterenol produces smaller elevations in cyclic AMP and in the cyclic AMP-dependent protein kinase activity ratio of newborn chick as compared to embryonic chick myocardium. Differences in the ability of isoproterenol to elevate cyclic AMP in the different preparations are not accompanied by appropriate changes in the adenylate cyclase or phosphodiesterase activities of the corresponding broken cell preparations. Studies with the phosphodiesterase inhibitor, Ro 20 1724 indicate that the changes in the ability of isoproterenol to elevate cyclic AMP in the developing chick myocardium are due to changes in the metabolism of the cyclic nucleotide by phosphodiesterase.", "contents": "Effects of isoproterenol on cyclic AMP and cyclic AMP-dependent protein kinase in developing chick myocardium. Embryonic chick (7-9 day) and newborn chick myocardia contain one major peak of cyclic AMP-dependent protein kinase activity as assessed by DEAE-cellulose chromatography. Evidence is presented that the cyclic AMP-dependent protein kinase activity ratios (activity in absence of cyclic AMP/activity in presence of added cyclic AMP) of homogenates prepared with low ionic strength buffer reflect the endogenous activation state of the enzyme. The cyclic AMP content of newborn chick myocardium is lower than that of 7--9 day embryonic chick myocardium; the baseline cyclic AMP-dependent protein kinase activity is correspondingly reduced. Isoproterenol produces smaller elevations in cyclic AMP and in the cyclic AMP-dependent protein kinase activity ratio of newborn chick as compared to embryonic chick myocardium. Differences in the ability of isoproterenol to elevate cyclic AMP in the different preparations are not accompanied by appropriate changes in the adenylate cyclase or phosphodiesterase activities of the corresponding broken cell preparations. Studies with the phosphodiesterase inhibitor, Ro 20 1724 indicate that the changes in the ability of isoproterenol to elevate cyclic AMP in the developing chick myocardium are due to changes in the metabolism of the cyclic nucleotide by phosphodiesterase."}
{"id": "PMID:200279", "title": "A simple and defined method to study calcification by isolated matrix vesicles. Effect of ATP and vesicle phosphatase.", "content": "A simplified and defined system was developed to study in vitro calcium phosphate deposition by isolated matrix vesicles from rabbit growth plate cartilage, and to examine the relationship between vesicle phosphatase and calcium deposition. Samples of suspended vesicles containing 25 microgram of protein, were incubated for 2 h in a 45Ca-labelled solution with 2.2 mM Ca2+, 1.6 mM PO 3/4-and 1 mM ATP at pH 7.6. Calcium deposition was related to the amount of PO4 hydrolysed by matrix vesicle phosphatases from ATP and other phosphate esters. Ca2+ or Mg2+ was found to stimulate matrix vesicle ATPase, but the hydrolysis of phosphoenolpyruvate, glucose 1-phosphate, beta-glycerol phosphate and AMP was independent of either cation. All of the above substrates supported calcium deposition. 1 mM ATP was more effective than 5 mM in supporting calcium deposition, indicating inhibition of mineralization at higher ATP concentrations. Our results suggest that, in addition to concentrating calcium, vesicles provide phosphate from ATP for mineral formation and at the same time remove the inhibitory effect of ATP upon mineral deposition.", "contents": "A simple and defined method to study calcification by isolated matrix vesicles. Effect of ATP and vesicle phosphatase. A simplified and defined system was developed to study in vitro calcium phosphate deposition by isolated matrix vesicles from rabbit growth plate cartilage, and to examine the relationship between vesicle phosphatase and calcium deposition. Samples of suspended vesicles containing 25 microgram of protein, were incubated for 2 h in a 45Ca-labelled solution with 2.2 mM Ca2+, 1.6 mM PO 3/4-and 1 mM ATP at pH 7.6. Calcium deposition was related to the amount of PO4 hydrolysed by matrix vesicle phosphatases from ATP and other phosphate esters. Ca2+ or Mg2+ was found to stimulate matrix vesicle ATPase, but the hydrolysis of phosphoenolpyruvate, glucose 1-phosphate, beta-glycerol phosphate and AMP was independent of either cation. All of the above substrates supported calcium deposition. 1 mM ATP was more effective than 5 mM in supporting calcium deposition, indicating inhibition of mineralization at higher ATP concentrations. Our results suggest that, in addition to concentrating calcium, vesicles provide phosphate from ATP for mineral formation and at the same time remove the inhibitory effect of ATP upon mineral deposition."}
{"id": "PMID:200280", "title": "Studies on mannose-containing glycopeptides from a normal and an SV40 transformed human cell.", "content": "The oligosaccharide moiety of cell-surface mannose-labelled glycopeptides from a normal (WI38) and an SV40 transformed cell (W118Va) have been investigated using specific glycosidases. Partially purified mannose-containing glycopeptides were separated into acidic and neutral species by high voltage paper electrophoresis. Endo-beta-N-acetylgucosaminidase D, in the presence of three exoglycosidases, released from the acidic glycopeptides of non-growing cells a product completely absent in growing cells. However, the acidic species from growing WI18 Va and WI38 were found to be similar in the products released by enzyme digestion. The neutral species from growing normal cells contained a proportion of the glycopeptides resistant to endoglycosidase D while those from the non-growing cells were almost free of these resistant species. The SV40 transformed cells were further enriched, when compared to normal cells (WI38), in these neutral resistant species. We suggest that the oligomannosyl core of the majority of the susceptible species contains three mannose residues while that of the resistant species contains between six and eight.", "contents": "Studies on mannose-containing glycopeptides from a normal and an SV40 transformed human cell. The oligosaccharide moiety of cell-surface mannose-labelled glycopeptides from a normal (WI38) and an SV40 transformed cell (W118Va) have been investigated using specific glycosidases. Partially purified mannose-containing glycopeptides were separated into acidic and neutral species by high voltage paper electrophoresis. Endo-beta-N-acetylgucosaminidase D, in the presence of three exoglycosidases, released from the acidic glycopeptides of non-growing cells a product completely absent in growing cells. However, the acidic species from growing WI18 Va and WI38 were found to be similar in the products released by enzyme digestion. The neutral species from growing normal cells contained a proportion of the glycopeptides resistant to endoglycosidase D while those from the non-growing cells were almost free of these resistant species. The SV40 transformed cells were further enriched, when compared to normal cells (WI38), in these neutral resistant species. We suggest that the oligomannosyl core of the majority of the susceptible species contains three mannose residues while that of the resistant species contains between six and eight."}
{"id": "PMID:200282", "title": "[Study of mechanisms of photoreceptor membrane destabilization under modifying action of oxygen].", "content": "Induction of lipid peroxidation in the rod outer segments (ROS) of frog retina results in fragmentation of photoreceptor disc membranes and solubilization of lipoprotein rhodopsin complexes (sedimentation coefficient 2.7S). The substrates of lipid autooxidation are mainly docosahexa- and docosapentaenoyl residues of phosphatidyl ethanolamine. Large fragments (precipitation at 5000 gX30 min) and small vesicles (precipitation at 40 000 gX60 min; average diameter 1000 A) formed from lipoperoxidized ROS differ both in their chemical composition and structural organization. In small vesicles the content of O2-modified polyenoic acyls in the phospholipids is 3,7 times higher as compared to large fragments. Correspondingly, the capacity of hydrophobic areas in the small vesicle membranes evaluated by EPR spin-probing technique is lower than in the large fragments. A mechanism of the photoreceptor membrane destabilization under modification by molecular oxygen is proposed. It is based on a decrease in the value of surface tension upon accumulation of lipid peroxidation products in ROS, the former possessing the properties of non-ionic detergents.", "contents": "[Study of mechanisms of photoreceptor membrane destabilization under modifying action of oxygen]. Induction of lipid peroxidation in the rod outer segments (ROS) of frog retina results in fragmentation of photoreceptor disc membranes and solubilization of lipoprotein rhodopsin complexes (sedimentation coefficient 2.7S). The substrates of lipid autooxidation are mainly docosahexa- and docosapentaenoyl residues of phosphatidyl ethanolamine. Large fragments (precipitation at 5000 gX30 min) and small vesicles (precipitation at 40 000 gX60 min; average diameter 1000 A) formed from lipoperoxidized ROS differ both in their chemical composition and structural organization. In small vesicles the content of O2-modified polyenoic acyls in the phospholipids is 3,7 times higher as compared to large fragments. Correspondingly, the capacity of hydrophobic areas in the small vesicle membranes evaluated by EPR spin-probing technique is lower than in the large fragments. A mechanism of the photoreceptor membrane destabilization under modification by molecular oxygen is proposed. It is based on a decrease in the value of surface tension upon accumulation of lipid peroxidation products in ROS, the former possessing the properties of non-ionic detergents."}
{"id": "PMID:200283", "title": "[Some characteristics of mitochondrial multienzyme systems from rat liver mitochondria after heating of rats].", "content": "A character of rat liver mitochondria degradation after the heat treatment of animals is studied. It is found that mitochondria under the effect of elevated temperature do not considerably change their functional characteristics and thus they are capable to provide the normal rate of ATP synthesis, the rate of succinate oxidation being slightly increased. At the same time the heating caused the degradation of mitochondria which results in the decrease of their thermostability, in the increased susceptibility to lytic effect of trypsin and phospholipase D, and in the activation of succinate dehydrogenase and cytochrome c oxidase. The mitochondria degradation is due to the formation of \"latent impairments\" in the structure of mitochondria.", "contents": "[Some characteristics of mitochondrial multienzyme systems from rat liver mitochondria after heating of rats]. A character of rat liver mitochondria degradation after the heat treatment of animals is studied. It is found that mitochondria under the effect of elevated temperature do not considerably change their functional characteristics and thus they are capable to provide the normal rate of ATP synthesis, the rate of succinate oxidation being slightly increased. At the same time the heating caused the degradation of mitochondria which results in the decrease of their thermostability, in the increased susceptibility to lytic effect of trypsin and phospholipase D, and in the activation of succinate dehydrogenase and cytochrome c oxidase. The mitochondria degradation is due to the formation of \"latent impairments\" in the structure of mitochondria."}
{"id": "PMID:200284", "title": "[Investigation of Endomyces magnusii respiratory system. Characteristics of mitochondria from cells grown in the presence of antimycin A].", "content": "Mitochondria from AA-cells are a unique model with separately finctioning 1st and 3rd points of energy coupling and with completely blocked 2nd coupling point. In vivo the terminal segment of the respiratory chain does not operate, cytochromes c and a+a3 remain oxidized, and dominating terminal oxidase appears to be a component inhibiting by salicylhydroxamate and bound with the respiratory chain via cytochromes b or ubiquinone pool. The blocking of the 2nd coupling point is due to firm and, probably, quantitative binding of AA with cytochromes b, especially with b559, and also to a partial denaturation of the complex III.", "contents": "[Investigation of Endomyces magnusii respiratory system. Characteristics of mitochondria from cells grown in the presence of antimycin A]. Mitochondria from AA-cells are a unique model with separately finctioning 1st and 3rd points of energy coupling and with completely blocked 2nd coupling point. In vivo the terminal segment of the respiratory chain does not operate, cytochromes c and a+a3 remain oxidized, and dominating terminal oxidase appears to be a component inhibiting by salicylhydroxamate and bound with the respiratory chain via cytochromes b or ubiquinone pool. The blocking of the 2nd coupling point is due to firm and, probably, quantitative binding of AA with cytochromes b, especially with b559, and also to a partial denaturation of the complex III."}
{"id": "PMID:200285", "title": "[NAD-dependent formate dehydrogenase from methylotrophic bacteria. Isolation and properties].", "content": "NAD-Dependent formate dehydrogenase (FDH) has been isolated from methylotrophyc strain Bacterium sp 1 by (NH4)2SO4 fractionation of cell extract, ion-exchange chromatography and preparative isotachophoresis. Preparation of FDH is homogeneous in analytical polyacrylamide gel electrophoresis and under ultracentrifugation. Sedimentation coefficient of FDH is 4.9S. Mikhaelis constants are 1.1-10(-4) M for NAD and 1.5-10(-2) M for formate. In the absence of sulfhydril compounds FDH is unstable, but it is stable in the presence of mercaptoethanol or ditiotreitol.", "contents": "[NAD-dependent formate dehydrogenase from methylotrophic bacteria. Isolation and properties]. NAD-Dependent formate dehydrogenase (FDH) has been isolated from methylotrophyc strain Bacterium sp 1 by (NH4)2SO4 fractionation of cell extract, ion-exchange chromatography and preparative isotachophoresis. Preparation of FDH is homogeneous in analytical polyacrylamide gel electrophoresis and under ultracentrifugation. Sedimentation coefficient of FDH is 4.9S. Mikhaelis constants are 1.1-10(-4) M for NAD and 1.5-10(-2) M for formate. In the absence of sulfhydril compounds FDH is unstable, but it is stable in the presence of mercaptoethanol or ditiotreitol."}
{"id": "PMID:200289", "title": "The biochemical basis of memory.", "content": "Several lines of research have indicated that the metabolism of both RNA and protein in the brain are important for permanent learning. One problem is to distinguish learning from stimulation per se, and whether it is meaningful to do so. Another problem is the biochemical interpretation of experiments using tracer precursor techniques. Evidence for the involvement of hormones such as ACTH as mediators of the biochemical responses and perhaps as stimulators of learning is discussed.", "contents": "The biochemical basis of memory. Several lines of research have indicated that the metabolism of both RNA and protein in the brain are important for permanent learning. One problem is to distinguish learning from stimulation per se, and whether it is meaningful to do so. Another problem is the biochemical interpretation of experiments using tracer precursor techniques. Evidence for the involvement of hormones such as ACTH as mediators of the biochemical responses and perhaps as stimulators of learning is discussed."}
{"id": "PMID:200290", "title": "Histochemical studies on the EBV-determined nuclear antigen (EBNA).", "content": "The EBV-determined nuclear antigen (EBNA) was studied with regard to several histochemical properties. Proteolytic enzymes destroyed EBNA staining. RNAse DNAse and hyaluronidase had no effect on the number of EBNA positive cells. Intensive treatment with DNAse weakened the chromosomal fluorescence of EBNA, whereas the staining of interphase nuclei was relatively enzyme resistant. When EBV-associated soluble complement-fixing antigen of Raji cells (CFA-R) was added to methanolacetic acid-fixed chicken red blood cells, brilliant and specific EBNA staining was obtained by anti-complement fluorescence (ACIF) with anti-EBNA positive sera. DNAse treatment abolished the ability of the nuclei to bind the antigen (CFA-R), whereas DNAse treatment following CFA-R antigen binding had no effect on the ACIF staining. EBNA was relatively heat stable. Somewhat weakened, but still fully positive EBNA reaction was obtained after 56 degrees C heating for 30 minutes in BSS. Periodate destroyed the EBNA reaction. Formaldehyde also abolished the staining, whereas methanol, acetone, methanol-acetone and methanol-hexyleneglycol-water preserved the staining relatively well.", "contents": "Histochemical studies on the EBV-determined nuclear antigen (EBNA). The EBV-determined nuclear antigen (EBNA) was studied with regard to several histochemical properties. Proteolytic enzymes destroyed EBNA staining. RNAse DNAse and hyaluronidase had no effect on the number of EBNA positive cells. Intensive treatment with DNAse weakened the chromosomal fluorescence of EBNA, whereas the staining of interphase nuclei was relatively enzyme resistant. When EBV-associated soluble complement-fixing antigen of Raji cells (CFA-R) was added to methanolacetic acid-fixed chicken red blood cells, brilliant and specific EBNA staining was obtained by anti-complement fluorescence (ACIF) with anti-EBNA positive sera. DNAse treatment abolished the ability of the nuclei to bind the antigen (CFA-R), whereas DNAse treatment following CFA-R antigen binding had no effect on the ACIF staining. EBNA was relatively heat stable. Somewhat weakened, but still fully positive EBNA reaction was obtained after 56 degrees C heating for 30 minutes in BSS. Periodate destroyed the EBNA reaction. Formaldehyde also abolished the staining, whereas methanol, acetone, methanol-acetone and methanol-hexyleneglycol-water preserved the staining relatively well."}
{"id": "PMID:200291", "title": "Poland syndrome: a concept of pathogenesis based on limb bud embryology.", "content": "A study of 15 patients as well as a review of the literature was made to determine the etiology of Poland syndrome. Neither the associated pathologic features nor any pattern of prenatal factors were helpful in revealing an etiology. A theory of primary nerve root dysgenesis was disproven. However, a concept of a localized insult at a particular embryonic stage based on known limb bud development is presented as a possible explanation of pathogenesis.", "contents": "Poland syndrome: a concept of pathogenesis based on limb bud embryology. A study of 15 patients as well as a review of the literature was made to determine the etiology of Poland syndrome. Neither the associated pathologic features nor any pattern of prenatal factors were helpful in revealing an etiology. A theory of primary nerve root dysgenesis was disproven. However, a concept of a localized insult at a particular embryonic stage based on known limb bud development is presented as a possible explanation of pathogenesis."}
{"id": "PMID:200293", "title": "Clinical aspects of gene expression.", "content": "1. Expression and nonexpressin of genetic information may be viewed in relationship to the biologic structures that express or do not express the genetic information. We suggest defining expressivity as the quality of expression of genetic information in cells, tissues, organs, etc, of individuals, defining penetrance as the quality of expression of genetic information in an individual organism as a whole, and using a new term, phenotrance, to describe the quality of expression of genetic information in generations. 2. Decreased phenotrance may be indicated by \"incompletely dominant\" inheritance, by conditions for which \"dominant\" as well as \"recessive\" inheritance has been reported, or by disorders with sporadic occurrence in most and familial occurrence in some instances. The human conditions with decreased phenotrance that we have studied indicate that there are different types of decreased phenotrance. 3. The mechanisms for decreased phenotrance in man may correspond to certain genetic mechanisms that have been studied in lower organisms, such as delayed mutation, replicating instabilities, controlling elements, extrachromosomal inheritance, and others.", "contents": "Clinical aspects of gene expression. 1. Expression and nonexpressin of genetic information may be viewed in relationship to the biologic structures that express or do not express the genetic information. We suggest defining expressivity as the quality of expression of genetic information in cells, tissues, organs, etc, of individuals, defining penetrance as the quality of expression of genetic information in an individual organism as a whole, and using a new term, phenotrance, to describe the quality of expression of genetic information in generations. 2. Decreased phenotrance may be indicated by \"incompletely dominant\" inheritance, by conditions for which \"dominant\" as well as \"recessive\" inheritance has been reported, or by disorders with sporadic occurrence in most and familial occurrence in some instances. The human conditions with decreased phenotrance that we have studied indicate that there are different types of decreased phenotrance. 3. The mechanisms for decreased phenotrance in man may correspond to certain genetic mechanisms that have been studied in lower organisms, such as delayed mutation, replicating instabilities, controlling elements, extrachromosomal inheritance, and others."}
{"id": "PMID:200294", "title": "[Isoenzyme pattern of acid phosphatase in epstein-barr-virus-DNA positive permanent growing lymphoid cell lines (author's transl)].", "content": "The expression of acid phosphatases is cytochemically one of the most important features in permanent growing B-cell-lines. In few cell lines acid phosphatase is resistant against tartrate. Tartrate resistant isoenzyme 5 with components a and b can be demonstrated in monocytes, lymphocytes, chronic lymphatic leucemic cells and especially in hairy cells as well as in cell lines derived from a healthy donor. Fractionation of acid phosphatase by gelelectrophoresis in separated lymphocytes demonstrates especially isoenzyme 3, in separated macrophages isoenzyme 4. Isoenzyme 4 could not be detected in several cell lines. It is therefore concluded that these cell lines are probably derived from lymphocytic precursors. Cell lines with isoenzyme 4 may be the result of a facultative hybridisation between lymphocytes and monocytes. Profiles of acid phosphatases in virus-negative cell lines (Ramos, BJAB) were not significantly altered by conversion with EBV.", "contents": "[Isoenzyme pattern of acid phosphatase in epstein-barr-virus-DNA positive permanent growing lymphoid cell lines (author's transl)]. The expression of acid phosphatases is cytochemically one of the most important features in permanent growing B-cell-lines. In few cell lines acid phosphatase is resistant against tartrate. Tartrate resistant isoenzyme 5 with components a and b can be demonstrated in monocytes, lymphocytes, chronic lymphatic leucemic cells and especially in hairy cells as well as in cell lines derived from a healthy donor. Fractionation of acid phosphatase by gelelectrophoresis in separated lymphocytes demonstrates especially isoenzyme 3, in separated macrophages isoenzyme 4. Isoenzyme 4 could not be detected in several cell lines. It is therefore concluded that these cell lines are probably derived from lymphocytic precursors. Cell lines with isoenzyme 4 may be the result of a facultative hybridisation between lymphocytes and monocytes. Profiles of acid phosphatases in virus-negative cell lines (Ramos, BJAB) were not significantly altered by conversion with EBV."}
{"id": "PMID:200295", "title": "[Fluorinated pyrimidines administered by percutaneous arterial perfusion in primary or secondary cancers of the liver].", "content": "The results of a study based on intraaterial therapy applied to 65 cases of hepatic cancers (among which 42 cases of metastases of recto-colitic origin and 8 cases of primitive hepatomas) are reported. The catheters are insected percutaneously through the left brachial artery. After achort term treatment with Fluoro-Uracil FUDR is given continuously for over 20 weeks on the average, in ambulatory practice, using a Watkins chronofusor. A subjective response is reported in 88 p. 100 of the cases, an objective one in 74 p. 100. The mean survival time reckoning from the date of diagnosis is 16.6 months (it is somewhat longer in the cases of primitive hepatoma). The signs of systemic toxicity are frequent but mild; they seldom compel to discontinue the treatment. No death due to therapy has been register-d. The results are at least as good and even better with transcutaneous catheters than with catheters surgically inserted in the abdomen. They should encourage a wide spread of the method.", "contents": "[Fluorinated pyrimidines administered by percutaneous arterial perfusion in primary or secondary cancers of the liver]. The results of a study based on intraaterial therapy applied to 65 cases of hepatic cancers (among which 42 cases of metastases of recto-colitic origin and 8 cases of primitive hepatomas) are reported. The catheters are insected percutaneously through the left brachial artery. After achort term treatment with Fluoro-Uracil FUDR is given continuously for over 20 weeks on the average, in ambulatory practice, using a Watkins chronofusor. A subjective response is reported in 88 p. 100 of the cases, an objective one in 74 p. 100. The mean survival time reckoning from the date of diagnosis is 16.6 months (it is somewhat longer in the cases of primitive hepatoma). The signs of systemic toxicity are frequent but mild; they seldom compel to discontinue the treatment. No death due to therapy has been register-d. The results are at least as good and even better with transcutaneous catheters than with catheters surgically inserted in the abdomen. They should encourage a wide spread of the method."}
{"id": "PMID:200297", "title": "The effects of alloxanate, nicotinic acid and imidazole on secretory processes and the activities of adenylate cyclase and 3',5'-AMP phosphodiesterase in cat pancreas.", "content": "1 Nicotinic acid and alloxanate inhibited water and electrolyte secretion in a dose-dependent fashion when added to the perfusate of the isolated saline-perfused pancreas of the cat stimulated by a supramaximal dose of secretin.2 There were no changes in the concentration of sodium or potassium secreted into the juice, but the anions exhibited changes which were related to flow rate. As the flow rate declined the chloride concentration increased with a reciprocal decrease in bicarbonate concentration.3 Nicotinic acid and alloxanate inhibited enzyme secretion stimulated by carbachol.4 Imidazole inhibited pancreatic electrolyte secretion, but stimulated amylase secretion. Atropine (0.14 muM) reduced the secretion of amylase but did not abolish the effect.5 Adenylate cyclase prepared from cat pancreas, was stimulated by the octapeptide of cholecystokinin-pancreozymin, secretin and sodium fluoride.6 Alloxanate strongly inhibited both basal and hormone-stimulated adenylate cyclase activity. Nicotinic acid and imidazole stimulated basal adenylate cyclase activity but had little effect on secretin-stimulated activity.7 Alloxanate, nicotinic acid and imidazole were all without effect on phosphodiesterase when tested in the presence of micromolar concentrations of adenosine 3',5'-monophosphate (cyclic AMP). At higher cyclic AMP concentrations (2 mM) alloxanate and nicotinic acid were without effect, whereas imidazole had a slight stimulatory effect at 10 mM which was more marked at 50 mM.8 Alloxanate (10 mM) strongly inhibited both basal and secretin-stimulated adenylate cyclase activity.9 It is concluded that the effects of nicotinic acid, alloxanate and imidazole on pancreatic secretion are not mediated entirely through their effects on the adenylate cyclase or phosphodiesterase enzyme systems.", "contents": "The effects of alloxanate, nicotinic acid and imidazole on secretory processes and the activities of adenylate cyclase and 3',5'-AMP phosphodiesterase in cat pancreas. 1 Nicotinic acid and alloxanate inhibited water and electrolyte secretion in a dose-dependent fashion when added to the perfusate of the isolated saline-perfused pancreas of the cat stimulated by a supramaximal dose of secretin.2 There were no changes in the concentration of sodium or potassium secreted into the juice, but the anions exhibited changes which were related to flow rate. As the flow rate declined the chloride concentration increased with a reciprocal decrease in bicarbonate concentration.3 Nicotinic acid and alloxanate inhibited enzyme secretion stimulated by carbachol.4 Imidazole inhibited pancreatic electrolyte secretion, but stimulated amylase secretion. Atropine (0.14 muM) reduced the secretion of amylase but did not abolish the effect.5 Adenylate cyclase prepared from cat pancreas, was stimulated by the octapeptide of cholecystokinin-pancreozymin, secretin and sodium fluoride.6 Alloxanate strongly inhibited both basal and hormone-stimulated adenylate cyclase activity. Nicotinic acid and imidazole stimulated basal adenylate cyclase activity but had little effect on secretin-stimulated activity.7 Alloxanate, nicotinic acid and imidazole were all without effect on phosphodiesterase when tested in the presence of micromolar concentrations of adenosine 3',5'-monophosphate (cyclic AMP). At higher cyclic AMP concentrations (2 mM) alloxanate and nicotinic acid were without effect, whereas imidazole had a slight stimulatory effect at 10 mM which was more marked at 50 mM.8 Alloxanate (10 mM) strongly inhibited both basal and secretin-stimulated adenylate cyclase activity.9 It is concluded that the effects of nicotinic acid, alloxanate and imidazole on pancreatic secretion are not mediated entirely through their effects on the adenylate cyclase or phosphodiesterase enzyme systems."}
{"id": "PMID:200298", "title": "Opiate binding and effect in ileum preparations from normal and morphine pretreated guinea-pigs.", "content": "1 Dose-response curves for normorphine in the absence and presence of naloxone have been obtained from myenteric plexus-longitudinal muscle strip preparations from normal and morphine pretreated guinea-pigs. In addition, the high affinity stereospecific binding of [3H]-etorphine has been measured in homogenates of the same tissue. 2 Higher concentrations of normorphine were required to produce 50% inhibition of the electrically stimulated contractions of strip preparations from morphine pretreated animals. There was also an increase in the slope of linearized dose-response curves in opiate-tolerant preparations. Maximum opiate effect was unchanged, and responses to exogenous acetylcholine were not affected by the pretreatment. 3 There was a slight increase in the apparent equilibrium constant for naloxone after morphine pretreatment. 4 Tolerance to opiate effect was not accompanied by a change in the affinity or number of stereospecific binding sites for [3H]-etorphine. Hill plots of [3H]-etorphine binding in both control and morphine pretreated preparations gave slopes close to unity. 5 Most of these results can be explained by the assumption that in tolerant preparations, a certain fractional opiate receptor occupation threshold must be exceeded before opiate effects become apparent. It is suggested that the tissue adapts toward a threshold equivalent to the mean receptor occupancy attained during the period of opiate drug pretreatment.", "contents": "Opiate binding and effect in ileum preparations from normal and morphine pretreated guinea-pigs. 1 Dose-response curves for normorphine in the absence and presence of naloxone have been obtained from myenteric plexus-longitudinal muscle strip preparations from normal and morphine pretreated guinea-pigs. In addition, the high affinity stereospecific binding of [3H]-etorphine has been measured in homogenates of the same tissue. 2 Higher concentrations of normorphine were required to produce 50% inhibition of the electrically stimulated contractions of strip preparations from morphine pretreated animals. There was also an increase in the slope of linearized dose-response curves in opiate-tolerant preparations. Maximum opiate effect was unchanged, and responses to exogenous acetylcholine were not affected by the pretreatment. 3 There was a slight increase in the apparent equilibrium constant for naloxone after morphine pretreatment. 4 Tolerance to opiate effect was not accompanied by a change in the affinity or number of stereospecific binding sites for [3H]-etorphine. Hill plots of [3H]-etorphine binding in both control and morphine pretreated preparations gave slopes close to unity. 5 Most of these results can be explained by the assumption that in tolerant preparations, a certain fractional opiate receptor occupation threshold must be exceeded before opiate effects become apparent. It is suggested that the tissue adapts toward a threshold equivalent to the mean receptor occupancy attained during the period of opiate drug pretreatment."}
{"id": "PMID:200306", "title": "Identification of respiratory motor neurons in the carp and determination of their firing characteristics and interconnections.", "content": "Motor neurons of the respiratory muscles of the carp, located in the medulla oblongata, are identified with a signal averaging technique. Analysis of the firing characteristics of these neurons provides data on their activity patterns under different circumstances. The results show that, on the one hand, the number of spikes a motor neuron fires per respiratory cycle depends on the respiratory intensity, and can even be as low as one action potential per respiration. On the other hand, with constant respiratory intensity, the activity of individual motor neurons can stop and be resumed again in periods of several minutes. During mechanical loading of respiration, action potential synchronization between specific respiratory muscles takes place. Possible neuronal circuits causing this synchronization, which is thought to increase the coordination of the muscular effort, are discussed.", "contents": "Identification of respiratory motor neurons in the carp and determination of their firing characteristics and interconnections. Motor neurons of the respiratory muscles of the carp, located in the medulla oblongata, are identified with a signal averaging technique. Analysis of the firing characteristics of these neurons provides data on their activity patterns under different circumstances. The results show that, on the one hand, the number of spikes a motor neuron fires per respiratory cycle depends on the respiratory intensity, and can even be as low as one action potential per respiration. On the other hand, with constant respiratory intensity, the activity of individual motor neurons can stop and be resumed again in periods of several minutes. During mechanical loading of respiration, action potential synchronization between specific respiratory muscles takes place. Possible neuronal circuits causing this synchronization, which is thought to increase the coordination of the muscular effort, are discussed."}
{"id": "PMID:200307", "title": "Modulation of electrical activity and cyclic nucleotide metabolism in molluscan nervous system by a peptide-containing nervous system extract.", "content": "A peptide-containing extract (PE) from Helix nervous system modifies the endogenous bursting pattern of electrical activity in Helix neurone F-1. This effect is similar to that induced in neuron F-1 by certain phosphodiesterase inhibitors and cAMP derivatives. The PE, and the vertebrate peptide hormones vasopressin and oxytocin, also cause an accumulation of cAMP in Helix ganglia in vitro. The factor in the PE which causes the cAMP accumulation is destroyed by Pronase, is lost on dialysis, and is stable to boiling. In all these respects it is identical to the factor which causes the change in neuronal electrical activity. The PE also stimulates adenylate cyclase activity in a crude membrane fraction prepared from Helix ganglion homogenates. This stimulation is abolished by prior dialysis of the PE, or pretreatment of the PE with pepsin, but is not affected by boiling of the PE. Pepsin-treated PE has no effect on electrical activity in neuron F-1. The adenylate cyclase-stimulating activity of the PE, like the factor which modifies neurone F-1 electrical activity, elutes in the void volume of a Sephadex G-10 column. The included volume of this column contains a factor which inhibits PE modification of neuronal electrical activity, and also inhibits both basal and PE-stimulated adenylate cyclase activity. The data are consistent with the possibility that cAMP mediates the effects of the PE on electrical activity in molluscan neurones.", "contents": "Modulation of electrical activity and cyclic nucleotide metabolism in molluscan nervous system by a peptide-containing nervous system extract. A peptide-containing extract (PE) from Helix nervous system modifies the endogenous bursting pattern of electrical activity in Helix neurone F-1. This effect is similar to that induced in neuron F-1 by certain phosphodiesterase inhibitors and cAMP derivatives. The PE, and the vertebrate peptide hormones vasopressin and oxytocin, also cause an accumulation of cAMP in Helix ganglia in vitro. The factor in the PE which causes the cAMP accumulation is destroyed by Pronase, is lost on dialysis, and is stable to boiling. In all these respects it is identical to the factor which causes the change in neuronal electrical activity. The PE also stimulates adenylate cyclase activity in a crude membrane fraction prepared from Helix ganglion homogenates. This stimulation is abolished by prior dialysis of the PE, or pretreatment of the PE with pepsin, but is not affected by boiling of the PE. Pepsin-treated PE has no effect on electrical activity in neuron F-1. The adenylate cyclase-stimulating activity of the PE, like the factor which modifies neurone F-1 electrical activity, elutes in the void volume of a Sephadex G-10 column. The included volume of this column contains a factor which inhibits PE modification of neuronal electrical activity, and also inhibits both basal and PE-stimulated adenylate cyclase activity. The data are consistent with the possibility that cAMP mediates the effects of the PE on electrical activity in molluscan neurones."}
{"id": "PMID:200309", "title": "A morphine-like factor in mammalian brain: analgesic activity in rats.", "content": "A partially purified morphine-like peptide 'enkephalin' (PPE) extract from bovine brain elicited pronounced apparent analgesia after injection into the periaqueductal gray matter of rat brain. This analgesia was reversed by the opiate antagonist naloxone in a dose-dependent fashion. Analgesia was more rapid in onset and much shorter in duration after PPE than after morphine administration. Analgesia was elicited only by those ion exchange column fractions of PPE that competed potently for opiate receptor binding. No analgesia could be detected when PPE or morphine injections were administered at a site 2 mm lateral to the periaqueductal gray matter. The potencies of synthetic methionine- and leucine-enkephalin in eliciting analgesia were less than 1% of those of partially purified enkephalin extracts when doses of equivalent ability to compete for opiate receptor binding were compared.", "contents": "A morphine-like factor in mammalian brain: analgesic activity in rats. A partially purified morphine-like peptide 'enkephalin' (PPE) extract from bovine brain elicited pronounced apparent analgesia after injection into the periaqueductal gray matter of rat brain. This analgesia was reversed by the opiate antagonist naloxone in a dose-dependent fashion. Analgesia was more rapid in onset and much shorter in duration after PPE than after morphine administration. Analgesia was elicited only by those ion exchange column fractions of PPE that competed potently for opiate receptor binding. No analgesia could be detected when PPE or morphine injections were administered at a site 2 mm lateral to the periaqueductal gray matter. The potencies of synthetic methionine- and leucine-enkephalin in eliciting analgesia were less than 1% of those of partially purified enkephalin extracts when doses of equivalent ability to compete for opiate receptor binding were compared."}
{"id": "PMID:200314", "title": "Analyses of relative protein content and distribution of histones in euchromatic and heterochromatic fractions.", "content": "Euchromatic and heterochromatic fractions obtained by autodigestion of mouse TLT (taper liver tumour) hepatoma chromatin (Paul, I. J & Duerksen, J. D. (1976) Arch. Biochem. Biophys. 174, 491-505) were analyzed for relative protein content and histone content. With one exception, all fractions had the same DNA to protein ratio. Similarly, the total histone to DNA ratio was also constant in all fractions. In addition, the relative contents of the major histones, H1, (H2A + H2B + H3), and H4, were also constant in all fractions.", "contents": "Analyses of relative protein content and distribution of histones in euchromatic and heterochromatic fractions. Euchromatic and heterochromatic fractions obtained by autodigestion of mouse TLT (taper liver tumour) hepatoma chromatin (Paul, I. J & Duerksen, J. D. (1976) Arch. Biochem. Biophys. 174, 491-505) were analyzed for relative protein content and histone content. With one exception, all fractions had the same DNA to protein ratio. Similarly, the total histone to DNA ratio was also constant in all fractions. In addition, the relative contents of the major histones, H1, (H2A + H2B + H3), and H4, were also constant in all fractions."}
{"id": "PMID:200315", "title": "Protein content and enzyme levels of cultured chick embryo cells treated with camptothecin and actinomycin D.", "content": "The alkaloid camptothecin uncouples the growth and adivision of chick embryo cells. At a moderate dose (0.5 microgram/ml) it inhibits the incorporation of thymidine but not of uridine and leucine and the cell protein content increases and reaches twice that of control after 4 days of treatment. Twelve hours after addition of the drug, the activities per cell of the mitochondrial enzymes poly A hydrolase (EC 3.1. 4.21), cytochrome c oxidase (EC 1.9.3.1), and succinate dehydrogenase (EC 1.3.99.1) are greater than that of the control and keep increasing for at least 96 H. The increase in the activities of the mitochondrial enzymes precede that of NADPH-cytochrome c reductase (EC 1.6.2.4) and cytidine triphosphatase (EC 3.6.1.15), which are microsomal and plasma membranes enzymes respectively. Actinomycin D (0.01 microgram/ml) also inhibits the multiplication of the chick cells and the synthesis of DNA. The protein content of the actinomycin D treated cells decreases to 70% of the control by day 2. Nevertheless, the activities of the mitochondrial enzymes increase over that of the control but to a smaller extent that with camptothecin. The activities of the enzymes of the other organelles are not stimulated. Camptothecin at a higher dose (5.0 microgram/ml) induces effects similar to those of actinomycin D.", "contents": "Protein content and enzyme levels of cultured chick embryo cells treated with camptothecin and actinomycin D. The alkaloid camptothecin uncouples the growth and adivision of chick embryo cells. At a moderate dose (0.5 microgram/ml) it inhibits the incorporation of thymidine but not of uridine and leucine and the cell protein content increases and reaches twice that of control after 4 days of treatment. Twelve hours after addition of the drug, the activities per cell of the mitochondrial enzymes poly A hydrolase (EC 3.1. 4.21), cytochrome c oxidase (EC 1.9.3.1), and succinate dehydrogenase (EC 1.3.99.1) are greater than that of the control and keep increasing for at least 96 H. The increase in the activities of the mitochondrial enzymes precede that of NADPH-cytochrome c reductase (EC 1.6.2.4) and cytidine triphosphatase (EC 3.6.1.15), which are microsomal and plasma membranes enzymes respectively. Actinomycin D (0.01 microgram/ml) also inhibits the multiplication of the chick cells and the synthesis of DNA. The protein content of the actinomycin D treated cells decreases to 70% of the control by day 2. Nevertheless, the activities of the mitochondrial enzymes increase over that of the control but to a smaller extent that with camptothecin. The activities of the enzymes of the other organelles are not stimulated. Camptothecin at a higher dose (5.0 microgram/ml) induces effects similar to those of actinomycin D."}
{"id": "PMID:200316", "title": "Transmissible gastroenteritis: demonstration of the virus from field specimens by means of cell culture and pig inoculation.", "content": "Isolation of transmissible gastroenteritis virus was attempted from segments of jejunum collected from piglets submitted for diagnosis of transmissible gastroenteritis. The virus was isolated more frequently in susceptible piglets than in pig kidney or pig thyroid cells. Practically, both cell systems were equally capable of demonstrating the virus when the tissue suspensions were sonicated. The pig thyroid cells prepared with glands collected from minimal disease pigs were preferred to the pig kidney cells for initial virus isolation because of their ability to respond to transmissible gastroenteritis virus with a progressive cytopathic effect. However, the pig thyroid cells, prepared from pool of glands collected in abattoirs, were often contaminated with parvoviruses and could not be used for diagnostic work. Controlled ultrasound treatments of the inoculum increased the frequency of virus isolation in both cell systems.", "contents": "Transmissible gastroenteritis: demonstration of the virus from field specimens by means of cell culture and pig inoculation. Isolation of transmissible gastroenteritis virus was attempted from segments of jejunum collected from piglets submitted for diagnosis of transmissible gastroenteritis. The virus was isolated more frequently in susceptible piglets than in pig kidney or pig thyroid cells. Practically, both cell systems were equally capable of demonstrating the virus when the tissue suspensions were sonicated. The pig thyroid cells prepared with glands collected from minimal disease pigs were preferred to the pig kidney cells for initial virus isolation because of their ability to respond to transmissible gastroenteritis virus with a progressive cytopathic effect. However, the pig thyroid cells, prepared from pool of glands collected in abattoirs, were often contaminated with parvoviruses and could not be used for diagnostic work. Controlled ultrasound treatments of the inoculum increased the frequency of virus isolation in both cell systems."}
{"id": "PMID:200312", "title": "A monosynaptic fiber track studied in vitro: evidence of a hippocampal CA1 associational system?", "content": "An excitatory afferent system previously undescribed in the in vitro slice was found to be present in the hippocampal CA1 stratum oriens. Evidence was provided that the system makes monosynaptic, en passage contact with CA1 pyramidal cells in the region of their basal dendrites. Slices from partially deafferented hippocampai were used in evaluating the possibility that the s. oriens pathway originated in the contralateral hippocampus. This possibility was not confirmed and the results were discussed in terms of an ipsilateral associational system in CA1 s. oriens.", "contents": "A monosynaptic fiber track studied in vitro: evidence of a hippocampal CA1 associational system? An excitatory afferent system previously undescribed in the in vitro slice was found to be present in the hippocampal CA1 stratum oriens. Evidence was provided that the system makes monosynaptic, en passage contact with CA1 pyramidal cells in the region of their basal dendrites. Slices from partially deafferented hippocampai were used in evaluating the possibility that the s. oriens pathway originated in the contralateral hippocampus. This possibility was not confirmed and the results were discussed in terms of an ipsilateral associational system in CA1 s. oriens."}
{"id": "PMID:200317", "title": "Cell mediated immunity in equine herpesvirus type 1 infection I. In vitro lymphocyte blastogenesis and serum neutralization antibody in normal parturient and aborting mares.", "content": "Blastic transformation of peripheral blood mononuclear cells and serum neutralization antibody levels for equine herpesivurs type 1 were measured in 19 mares from three farms at the time of termination of their pregnancy by normal foaling or viral abortion. The stimulation indexes of lymphocytes obtained from the mares from two farms (Farm 1 and 2) which had virus abortions, ranged from 2.1 to 10.8. But there was no significant difference in stimulation index levels between the aborting and normal foaling mares on these two farms. Equine herpesvirus type 1 was isolated from the mononuclear cells of one mare (No. 5) about two months after she aborted. The stimulation index of lymphocytes from that mare was not significantly different from that of other mares on these farms. Stimulation index of lymphocytes from the mares on one farm (Farm 3) where there was no virus abortion or previous history of virus abortion but were exposed to virus antigen from vaccination, ranged from 1.6 to 2.9. The serum neutralization antibody levels were low in most mares ranging from 1/4 to 1/20 and in three mares these were higher. There was no direct correlation between the levels of serum neutralization antibody and stimulation index of lymphocytes from the mares on these farms.", "contents": "Cell mediated immunity in equine herpesvirus type 1 infection I. In vitro lymphocyte blastogenesis and serum neutralization antibody in normal parturient and aborting mares. Blastic transformation of peripheral blood mononuclear cells and serum neutralization antibody levels for equine herpesivurs type 1 were measured in 19 mares from three farms at the time of termination of their pregnancy by normal foaling or viral abortion. The stimulation indexes of lymphocytes obtained from the mares from two farms (Farm 1 and 2) which had virus abortions, ranged from 2.1 to 10.8. But there was no significant difference in stimulation index levels between the aborting and normal foaling mares on these two farms. Equine herpesvirus type 1 was isolated from the mononuclear cells of one mare (No. 5) about two months after she aborted. The stimulation index of lymphocytes from that mare was not significantly different from that of other mares on these farms. Stimulation index of lymphocytes from the mares on one farm (Farm 3) where there was no virus abortion or previous history of virus abortion but were exposed to virus antigen from vaccination, ranged from 1.6 to 2.9. The serum neutralization antibody levels were low in most mares ranging from 1/4 to 1/20 and in three mares these were higher. There was no direct correlation between the levels of serum neutralization antibody and stimulation index of lymphocytes from the mares on these farms."}
{"id": "PMID:200313", "title": "Medullary unit responses to changes in local and hypothalamic temperatures in the cat.", "content": "Single unit activity was recorded with glass microelectrodes in the reticular formation of the medulla oblongata of cats lightly anesthetized with urethan, while medullary temperature was changed by surface irrigation with warm or cold artificial cerebrospinal fluid. In addition, water-perfusion thermodes were implanted over the preoptic anterior hypothalamus (POAH) region, and the effects of heating and cooling of the POAH on firing rate of medullary units were studied. One hundred and twenty-five temperature-sensitive neurons were studied in the medullary reticular formation. Out of these 125 neurons, 80 were warm-sensitive and 45 were cold-sensitive. Sixteen warm-sensitive medullary neurons were examined in responses to changes of POAH temperature. Ten units (62.5%) responded, and the remaining 6 units were not responsive to changes of the POAH temperature. Of 13 cold-sensitive neurons examined, 10 units (77.0%) responded. On the other hand, only 1 out of 7 (14.3%) temperature-insensitive neurons tested did respond to changes in the POAH temperature. These results suggest that the temperature signals sent out from thermosensitive structures in the hypothalamus might be transmitted to a major portion of temperature-sensitive neurons in the medullary reticular formation.", "contents": "Medullary unit responses to changes in local and hypothalamic temperatures in the cat. Single unit activity was recorded with glass microelectrodes in the reticular formation of the medulla oblongata of cats lightly anesthetized with urethan, while medullary temperature was changed by surface irrigation with warm or cold artificial cerebrospinal fluid. In addition, water-perfusion thermodes were implanted over the preoptic anterior hypothalamus (POAH) region, and the effects of heating and cooling of the POAH on firing rate of medullary units were studied. One hundred and twenty-five temperature-sensitive neurons were studied in the medullary reticular formation. Out of these 125 neurons, 80 were warm-sensitive and 45 were cold-sensitive. Sixteen warm-sensitive medullary neurons were examined in responses to changes of POAH temperature. Ten units (62.5%) responded, and the remaining 6 units were not responsive to changes of the POAH temperature. Of 13 cold-sensitive neurons examined, 10 units (77.0%) responded. On the other hand, only 1 out of 7 (14.3%) temperature-insensitive neurons tested did respond to changes in the POAH temperature. These results suggest that the temperature signals sent out from thermosensitive structures in the hypothalamus might be transmitted to a major portion of temperature-sensitive neurons in the medullary reticular formation."}
{"id": "PMID:200318", "title": "Detection and localization of aleutian disease virus and its antigens in vivo by immunoferritin technique.", "content": "Tissues from mink infected with aleutian disease virus were examined by the electron microscope for the presence of virus particles. Virus-like particles, measuring 22 nm in diameter, were observed in macrophages of spleen, mesenteric lymph node and in Kupffer cells in liver of mink ten to 13 days after infection. The virus-like particles were usually present in vacuoles inside the cytoplasm of macrophages and Kupffer cells and, occasionally, similar particles were observed inside the nucleus. Cells from uninfected mink did not contain such patricles. To correlate the existence of these virus-like particles with the presence of aleutian disease virus antigen in infected cells, tissues were processed for immunoferritin technique. It was found that aleutian disease virus antigen was present in vacuoles inside the cytoplasm of cells from the infected spleen, lymph node and liver, and that the location was similar to that of the 22 nm virus-like particles. In addition, some viral antigen was also detected as cytoplasmic granular material. The nuclei of some cells also contained aleutian disease virus antigen. The pattern of aleutian disease virus antigen was similar to the distribution of virus-like particles in cells of infected tissue. It is suggested that virus replication occurs inside the nucleus with subsequent accumulation of virus in the vacuoles of the cytoplasm.", "contents": "Detection and localization of aleutian disease virus and its antigens in vivo by immunoferritin technique. Tissues from mink infected with aleutian disease virus were examined by the electron microscope for the presence of virus particles. Virus-like particles, measuring 22 nm in diameter, were observed in macrophages of spleen, mesenteric lymph node and in Kupffer cells in liver of mink ten to 13 days after infection. The virus-like particles were usually present in vacuoles inside the cytoplasm of macrophages and Kupffer cells and, occasionally, similar particles were observed inside the nucleus. Cells from uninfected mink did not contain such patricles. To correlate the existence of these virus-like particles with the presence of aleutian disease virus antigen in infected cells, tissues were processed for immunoferritin technique. It was found that aleutian disease virus antigen was present in vacuoles inside the cytoplasm of cells from the infected spleen, lymph node and liver, and that the location was similar to that of the 22 nm virus-like particles. In addition, some viral antigen was also detected as cytoplasmic granular material. The nuclei of some cells also contained aleutian disease virus antigen. The pattern of aleutian disease virus antigen was similar to the distribution of virus-like particles in cells of infected tissue. It is suggested that virus replication occurs inside the nucleus with subsequent accumulation of virus in the vacuoles of the cytoplasm."}
{"id": "PMID:200319", "title": "Necrotizing encephalitis in skunks caused by Herpes simplex virus.", "content": "Herpes simplex virus was isolated from the brain of a wild skunk (Mephitis mephitis) which had clinical neurological disease. In the brain of this skunk and in brain of skunks inoculated intracerebrally, there were areas of necrosis in the grey matter of the cerebral cortex and to a lesser extent in the brain stem. Intranuclear inclusions occurred in neurons and glial cells with vascular cuffing by mononuclear cells and a few neutrophils. Skunks inoculated intravenously had extensive focal necrosis in the liver and adrenal glands.", "contents": "Necrotizing encephalitis in skunks caused by Herpes simplex virus. Herpes simplex virus was isolated from the brain of a wild skunk (Mephitis mephitis) which had clinical neurological disease. In the brain of this skunk and in brain of skunks inoculated intracerebrally, there were areas of necrosis in the grey matter of the cerebral cortex and to a lesser extent in the brain stem. Intranuclear inclusions occurred in neurons and glial cells with vascular cuffing by mononuclear cells and a few neutrophils. Skunks inoculated intravenously had extensive focal necrosis in the liver and adrenal glands."}
{"id": "PMID:200320", "title": "Effect of age and pregnancy on the antibody and cell-mediated immune responses of horses to equine herpesvirus 1.", "content": "The cell-mediated immune response and antibody response of horses of varying ages and of pregnant horses to equine herpesvirus 1 antigen were examined. Six to eight month old horses showed either no increase or slight increases in anti-equine herpesvirus 1 serum neutralizing antibody following vaccination and revaccination with a modified live equine herpesvirus 1 vaccine. However, these same horses showed a marked increase in the cell-mediated immune response to equine herpesvirus 1 as measured by the lymphocyte transformation test. Eighteen to 21 month old horses showed four to 64-fold increases in anti-equine herpesvirus 1 serum neutralizing antibody titer following vaccination, but the cell-mediated immune response to equine herpesvirus 1 was low or absent. Only after revaccination did they show an increased cell-mediated immune response to equine herpesvirus 1. The cell-mediated immune response of mares in the latter stages of pregnancy to equine herpesivurs 1 was suppressed although antibody titers increased as much as 16-fold following exposure to virulent equine herpesvirus 1.", "contents": "Effect of age and pregnancy on the antibody and cell-mediated immune responses of horses to equine herpesvirus 1. The cell-mediated immune response and antibody response of horses of varying ages and of pregnant horses to equine herpesvirus 1 antigen were examined. Six to eight month old horses showed either no increase or slight increases in anti-equine herpesvirus 1 serum neutralizing antibody following vaccination and revaccination with a modified live equine herpesvirus 1 vaccine. However, these same horses showed a marked increase in the cell-mediated immune response to equine herpesvirus 1 as measured by the lymphocyte transformation test. Eighteen to 21 month old horses showed four to 64-fold increases in anti-equine herpesvirus 1 serum neutralizing antibody titer following vaccination, but the cell-mediated immune response to equine herpesvirus 1 was low or absent. Only after revaccination did they show an increased cell-mediated immune response to equine herpesvirus 1. The cell-mediated immune response of mares in the latter stages of pregnancy to equine herpesivurs 1 was suppressed although antibody titers increased as much as 16-fold following exposure to virulent equine herpesvirus 1."}
{"id": "PMID:200321", "title": "Metabolic clearance rate of adrenocorticotropin in the rat.", "content": "The metabolic clearance rate (MCR) of adrenocorticotropin (ACTH) was estimated after the intravenous infusion of graded rates of the hormone (40-2560 muU/min per 100 g body weight) in rats pretreated with chlorpromazine, morphine, and Nembutal, a preparation which proved effective in blocking endogenous ACTH release. The hormone was infused over a period of 45 min, at which time the plasma ACTH concentration had reached a steady state. A specific and sensitive bioassay, based on the corticosterone production of dispersed adrenal cells, was used to measure the plasma ACTH concentration. With increasing infusion rates of ACTH, a threefold decrease in the MCR of ACTH was observed. Previous studies of our group have shown that the MCR of corticosterone increases as a function of the infusion rate of the steroid. It appears, therefore, that the metabolism of these two hormonal links of the hypothalamo-pituitary-adrenocortical axis vary in opposite fashions as a function of the secretion rate of the hormone.", "contents": "Metabolic clearance rate of adrenocorticotropin in the rat. The metabolic clearance rate (MCR) of adrenocorticotropin (ACTH) was estimated after the intravenous infusion of graded rates of the hormone (40-2560 muU/min per 100 g body weight) in rats pretreated with chlorpromazine, morphine, and Nembutal, a preparation which proved effective in blocking endogenous ACTH release. The hormone was infused over a period of 45 min, at which time the plasma ACTH concentration had reached a steady state. A specific and sensitive bioassay, based on the corticosterone production of dispersed adrenal cells, was used to measure the plasma ACTH concentration. With increasing infusion rates of ACTH, a threefold decrease in the MCR of ACTH was observed. Previous studies of our group have shown that the MCR of corticosterone increases as a function of the infusion rate of the steroid. It appears, therefore, that the metabolism of these two hormonal links of the hypothalamo-pituitary-adrenocortical axis vary in opposite fashions as a function of the secretion rate of the hormone."}
{"id": "PMID:200322", "title": "Quantitative study of alpha-adrenergic receptors in circular and longitudinal muscle of isthmus of rabbit fallopian tube and in rabbit aorta.", "content": "The affinity of phenylephrine (pD2 value) and KB value for phentolamine for the alpha-adrenergic receptors of circular and longitudinal muscle of isthmus of rabbit fallopian tube and rabbit aorta have been estimated. The affinity of both phenylephrine and phentolamine was significantly more for the alpha adrenoceptors of the longitudinal muscle of isthmus of rabbit fallopian tube and rabbit aorta than circular muscle of isthmus of fallopian tube. The results of this investigation suggest that alpha adrenoceptors of circular muscle of isthmus are atypical. If this holds good for the human fallopian tube, the development of selective alpha-adrenergic-receptor agonists and antagonists may be of potential practical application for the control of fertility.", "contents": "Quantitative study of alpha-adrenergic receptors in circular and longitudinal muscle of isthmus of rabbit fallopian tube and in rabbit aorta. The affinity of phenylephrine (pD2 value) and KB value for phentolamine for the alpha-adrenergic receptors of circular and longitudinal muscle of isthmus of rabbit fallopian tube and rabbit aorta have been estimated. The affinity of both phenylephrine and phentolamine was significantly more for the alpha adrenoceptors of the longitudinal muscle of isthmus of rabbit fallopian tube and rabbit aorta than circular muscle of isthmus of fallopian tube. The results of this investigation suggest that alpha adrenoceptors of circular muscle of isthmus are atypical. If this holds good for the human fallopian tube, the development of selective alpha-adrenergic-receptor agonists and antagonists may be of potential practical application for the control of fertility."}
{"id": "PMID:200323", "title": "Effect in vivo of beta-adrenergic stimulation, angiotensin II, dibutyryl cyclic AMP, and theophylline on tonin concentration in rat saliva and submaxillary gland.", "content": "Tonin (an enzyme present in rat submaxillary gland and saliva) has previously been shown to be able, unlike renin and reninlike substances, to release angiotensin II either directly by acting on an appropriate substrate or from angiotensin I. The administration of a beta-adrenergic drug, isoproterenol, produces a rise of tonin concentration in saliva without affecting its concentration in the submaxillary gland. Prior administration of a beta blocker, propranolol, partially prevents this effect. The administration of theophylline increases the tonin concentration in both saliva and the submaxillary gland, whereas dibutyryl cyclic AMP increases tonin concentration in the former. These results suggest that beta-adrenergic stimulation enhances both tonin release into the saliva and tonin synthesis in the submaxillary gland, and that these effects might be mediated by cyclic AMP. Infusion of angiotensin II blocked the stimulatory effect of isoproterenol on salivary tonin. 1Sar-8Ile-angiotensin II is both a weak antagonist of angiotensin II in this respect and a strong agonist in terms of blocking the effect of isoproterenol another role mirrored in other physiological mechanisms of derivatives of angiotensin II.", "contents": "Effect in vivo of beta-adrenergic stimulation, angiotensin II, dibutyryl cyclic AMP, and theophylline on tonin concentration in rat saliva and submaxillary gland. Tonin (an enzyme present in rat submaxillary gland and saliva) has previously been shown to be able, unlike renin and reninlike substances, to release angiotensin II either directly by acting on an appropriate substrate or from angiotensin I. The administration of a beta-adrenergic drug, isoproterenol, produces a rise of tonin concentration in saliva without affecting its concentration in the submaxillary gland. Prior administration of a beta blocker, propranolol, partially prevents this effect. The administration of theophylline increases the tonin concentration in both saliva and the submaxillary gland, whereas dibutyryl cyclic AMP increases tonin concentration in the former. These results suggest that beta-adrenergic stimulation enhances both tonin release into the saliva and tonin synthesis in the submaxillary gland, and that these effects might be mediated by cyclic AMP. Infusion of angiotensin II blocked the stimulatory effect of isoproterenol on salivary tonin. 1Sar-8Ile-angiotensin II is both a weak antagonist of angiotensin II in this respect and a strong agonist in terms of blocking the effect of isoproterenol another role mirrored in other physiological mechanisms of derivatives of angiotensin II."}
{"id": "PMID:200324", "title": "Effect of exogenous nucleotides on the candicidin fermentation.", "content": "Addition of cyclic-AMP (c-AMP) to Streptomyces griseus fermentations inhibited candicidin formation. In a phosphate-free resting cell system, c-AMP inhibited net candicidin formation and incorporation of labeled propionate and p-aminobenzoic acid into the antibiotic but did not inhibit protein synthesis. All nucleotides tested, regardless of the position of the phosphate ester, were effective inhibitors; nucleosides and free bases were not. Inhibition occurred whether the nucleotide was added early or late. The results indicate that inhibition of antibiotic formation by exogenous nucleotides, including cyclic nucleotides, is similar to the effect produced by inorganic phosphate.", "contents": "Effect of exogenous nucleotides on the candicidin fermentation. Addition of cyclic-AMP (c-AMP) to Streptomyces griseus fermentations inhibited candicidin formation. In a phosphate-free resting cell system, c-AMP inhibited net candicidin formation and incorporation of labeled propionate and p-aminobenzoic acid into the antibiotic but did not inhibit protein synthesis. All nucleotides tested, regardless of the position of the phosphate ester, were effective inhibitors; nucleosides and free bases were not. Inhibition occurred whether the nucleotide was added early or late. The results indicate that inhibition of antibiotic formation by exogenous nucleotides, including cyclic nucleotides, is similar to the effect produced by inorganic phosphate."}
{"id": "PMID:200325", "title": "The effect of ionic surface-active agents on macroconidial plasma membrane of Fusarium sulphureum.", "content": "A method was developed for direct assessment of changes in cytoplasmic volume and permeability of plasma membranes of intact cells to divalent cations. This technique, which ultilized an amphipathic spin label partitioning between intracellular aqueous and hydrophobic environments, allowed estimates of the proportion of cells in a homogenous population sustaining membrane damage associated with Ni+2 and water permeability and the rate at which such damage was induced. Several specific effects of cationic and anionic surfactants on the macroconidial plasma membranes of Fusarium sulphureum Schlect (isolate 1) were distinguished on the basis of detergent concentration and charge. The induction of water uptake by the cells was found to be an effect of dodecylguanidine acetate (Dodine), a cationic fungicide, at low concentration. At higher concentrations (greater than 5 X 10(-5) M) both the impermeability of the plasma membrane to divalent cations and the ability to accumulate actively L-phenylalanine were lost irreversibly and cell lysis occurred above 5 X 10(-4) M. Sodium dodecyl sulfate eliminated divalent cation impermeability more rapidly than Dodine but was less effective in inhibiting active transport function. An antagonistic effect between cationic and anionic detergents was observed.", "contents": "The effect of ionic surface-active agents on macroconidial plasma membrane of Fusarium sulphureum. A method was developed for direct assessment of changes in cytoplasmic volume and permeability of plasma membranes of intact cells to divalent cations. This technique, which ultilized an amphipathic spin label partitioning between intracellular aqueous and hydrophobic environments, allowed estimates of the proportion of cells in a homogenous population sustaining membrane damage associated with Ni+2 and water permeability and the rate at which such damage was induced. Several specific effects of cationic and anionic surfactants on the macroconidial plasma membranes of Fusarium sulphureum Schlect (isolate 1) were distinguished on the basis of detergent concentration and charge. The induction of water uptake by the cells was found to be an effect of dodecylguanidine acetate (Dodine), a cationic fungicide, at low concentration. At higher concentrations (greater than 5 X 10(-5) M) both the impermeability of the plasma membrane to divalent cations and the ability to accumulate actively L-phenylalanine were lost irreversibly and cell lysis occurred above 5 X 10(-4) M. Sodium dodecyl sulfate eliminated divalent cation impermeability more rapidly than Dodine but was less effective in inhibiting active transport function. An antagonistic effect between cationic and anionic detergents was observed."}
{"id": "PMID:200326", "title": "Isolation and characterization of catabolite repression-resistant mutants of Escherichia coli.", "content": "A method has been developed for the isolation of Escherichia coli mutants which are resistant to catabolic repression. The method is based on the fact that a mixture of glucose and gluconate inhibits the development of chemotactic motility in the wild type, but not in the mutants. A motile E. coli strain was mutagenized and grown in glucose and gluconate. Mutants which were able to swim into a tube containing a chemotactic attractant (aspartic acid) were isolated. Most of these mutants were able to produce beta-galactosidase in the presence of glucose and gluconate and were normal in their ability to degrade adenosine 3',5-cyclic monophosphate. Some of these mutants were defective in the glucose phosphotransferase system.", "contents": "Isolation and characterization of catabolite repression-resistant mutants of Escherichia coli. A method has been developed for the isolation of Escherichia coli mutants which are resistant to catabolic repression. The method is based on the fact that a mixture of glucose and gluconate inhibits the development of chemotactic motility in the wild type, but not in the mutants. A motile E. coli strain was mutagenized and grown in glucose and gluconate. Mutants which were able to swim into a tube containing a chemotactic attractant (aspartic acid) were isolated. Most of these mutants were able to produce beta-galactosidase in the presence of glucose and gluconate and were normal in their ability to degrade adenosine 3',5-cyclic monophosphate. Some of these mutants were defective in the glucose phosphotransferase system."}
{"id": "PMID:200327", "title": "Epitheliocystis disease in the striped bass Morone saxatilis from the Chesapeake Bay.", "content": "Epitheliocystis disease in the gills of the striped bass Morone saxatilis from Chesapeake Bay was studied using light and electron microscopy. The epitheliocystis infection appeared synchronous in that all capsules on a single host were at the same stage of development. The disease appeared to begin in a single cell on the gill lamella, which gradually enlarged to form a large cyst, encapsulated by a thick cellular capsule of epithelial origin. The epitheliocystis inclusion was filled with cells of the general morphology and size of rickettsiae; however, the infection was atypical for rickettsiae in that the cells had a dense central nucleoid region and they developed within an inclusion separated from the host cytoplasm.", "contents": "Epitheliocystis disease in the striped bass Morone saxatilis from the Chesapeake Bay. Epitheliocystis disease in the gills of the striped bass Morone saxatilis from Chesapeake Bay was studied using light and electron microscopy. The epitheliocystis infection appeared synchronous in that all capsules on a single host were at the same stage of development. The disease appeared to begin in a single cell on the gill lamella, which gradually enlarged to form a large cyst, encapsulated by a thick cellular capsule of epithelial origin. The epitheliocystis inclusion was filled with cells of the general morphology and size of rickettsiae; however, the infection was atypical for rickettsiae in that the cells had a dense central nucleoid region and they developed within an inclusion separated from the host cytoplasm."}
{"id": "PMID:200328", "title": "Inhibition of antigen and mitogen-induced lymphocyte transformation by fetal calf serum.", "content": "Use of fetal calf serum as a serum supplement in whole blood microcultures of human lymphocytes resulted in a significant suppression of in vitro stimulation with herpes simplex virus (type 1) antigen, purified protein derivative, and phytohemagglutinin. If the response to viral antigen is weak in autologous serum it may be completely missed if cultures are carried out in fetal calf serum.", "contents": "Inhibition of antigen and mitogen-induced lymphocyte transformation by fetal calf serum. Use of fetal calf serum as a serum supplement in whole blood microcultures of human lymphocytes resulted in a significant suppression of in vitro stimulation with herpes simplex virus (type 1) antigen, purified protein derivative, and phytohemagglutinin. If the response to viral antigen is weak in autologous serum it may be completely missed if cultures are carried out in fetal calf serum."}
{"id": "PMID:200329", "title": "Protective effect of polymyxin B sulfate in experimental meningococcal infection in mice.", "content": "The mouse model of intraperitoneal meningococcal sepsis was used to evaluate the antiendotoxic activity of polymyxin B sulfate independent of its antibiotic effects. Administered either before or after the infective challenge therapeutic doses of polymyxin B sulfate produced small but significant increases in survival over unprotected animals. These results also suggest that endotoxin contributes to the outcome in this variety of Gram-negative infection.", "contents": "Protective effect of polymyxin B sulfate in experimental meningococcal infection in mice. The mouse model of intraperitoneal meningococcal sepsis was used to evaluate the antiendotoxic activity of polymyxin B sulfate independent of its antibiotic effects. Administered either before or after the infective challenge therapeutic doses of polymyxin B sulfate produced small but significant increases in survival over unprotected animals. These results also suggest that endotoxin contributes to the outcome in this variety of Gram-negative infection."}
{"id": "PMID:200330", "title": "The response of Azotobacter chroococcum to oxygen: superoxide-mediated effects.", "content": "Nitrogenase in Azotobacter chroococcum whole cells was inhibited by enzymically generated superoxide anion (O2-), hydrogen peroxide, and ethyl hydrogen peroxide. The degree of inhibition produced by O2- was related to the quantity of oxygen supplied to the organisms in continuous cultures. O2- also inhibited oxygen uptake by whole cells. These O2- mediated inhibitions were prevented by bovine superoxide dismutase. The quantities of superoxide dismutase (SOD), and catalase associated with cells grown under varying oxygen concentrations were determined. The role of hydrogen peroxide, and of the hydroxyl radical (.OH) in nitrogenase inhibition was examined. The response of Azotobacter chroococum to oxygen was evaluated with respect to the observed effects of O2- on the organism, and some explanation is given to account for nitrogenase sensitivity to oxygen.", "contents": "The response of Azotobacter chroococcum to oxygen: superoxide-mediated effects. Nitrogenase in Azotobacter chroococcum whole cells was inhibited by enzymically generated superoxide anion (O2-), hydrogen peroxide, and ethyl hydrogen peroxide. The degree of inhibition produced by O2- was related to the quantity of oxygen supplied to the organisms in continuous cultures. O2- also inhibited oxygen uptake by whole cells. These O2- mediated inhibitions were prevented by bovine superoxide dismutase. The quantities of superoxide dismutase (SOD), and catalase associated with cells grown under varying oxygen concentrations were determined. The role of hydrogen peroxide, and of the hydroxyl radical (.OH) in nitrogenase inhibition was examined. The response of Azotobacter chroococum to oxygen was evaluated with respect to the observed effects of O2- on the organism, and some explanation is given to account for nitrogenase sensitivity to oxygen."}
{"id": "PMID:200332", "title": "Chemotherapy of malignant fibrous histiocytoma: a Southwest Oncology Group report.", "content": "Malignant fibrous histiocytoma is a rare tumor, which constitutes 3-4% of the soft tissue sarcomas. It occurs with maximum frequency in the sixth and seventh decades of life and has a distinct male preponderance. In two-thirds of the patients an extremity is the primary site and approximately one-half develop local recurrences and one-half, distant metastases. Response to combination chemotherapy occurred in 33%, a rate similar to that seen in other sarcomas.", "contents": "Chemotherapy of malignant fibrous histiocytoma: a Southwest Oncology Group report. Malignant fibrous histiocytoma is a rare tumor, which constitutes 3-4% of the soft tissue sarcomas. It occurs with maximum frequency in the sixth and seventh decades of life and has a distinct male preponderance. In two-thirds of the patients an extremity is the primary site and approximately one-half develop local recurrences and one-half, distant metastases. Response to combination chemotherapy occurred in 33%, a rate similar to that seen in other sarcomas."}
{"id": "PMID:200333", "title": "Human leukemic \"null\" cell line (NALL-1).", "content": "A human lymphoblast cell line, NALL-1, was established from the peripheral blood of a patient with acute lymphoblastic leukemia (ALL). NALL-1 cells had neither properties of T and B cells nor Epstein-Barr virus (EBV). Many characteristics of the NALL-1 line were distinct from those of numerous EBV-positive lymphoblastoid cell lines previously reported. NALL-1 cells are considered to have originated from the donor's leukemic cells on the basis of their cytogenetic, morphologic and functional features. The NALL-1 line is the first human leukemic \"null\" cell line derived from ALL. The significance of this cell line is disscussed.", "contents": "Human leukemic \"null\" cell line (NALL-1). A human lymphoblast cell line, NALL-1, was established from the peripheral blood of a patient with acute lymphoblastic leukemia (ALL). NALL-1 cells had neither properties of T and B cells nor Epstein-Barr virus (EBV). Many characteristics of the NALL-1 line were distinct from those of numerous EBV-positive lymphoblastoid cell lines previously reported. NALL-1 cells are considered to have originated from the donor's leukemic cells on the basis of their cytogenetic, morphologic and functional features. The NALL-1 line is the first human leukemic \"null\" cell line derived from ALL. The significance of this cell line is disscussed."}
{"id": "PMID:200334", "title": "Bronchiolo-alveolar carcinoma: a Clara cell tumor?", "content": "The cell of origin, and indeed the very existence, of bronchiolo-alveolar carcinoma have long been the subject of debate. Published cases have demonstrated the presence of type II pneumocytes in some tumors, while others have been composed of mucus-secreting bronchiolar cells. A case of bronchiolo-alveolar carcinoma is presented in which the ultrastructure indicates an origin from Clara cells, but in which some cells contain polymorphous and lamellar bodies, It is concluded that bronchiolo-alveolar carcinoma is a primary lung tumor derived from the terminal airways and in the majority of cases from the bronchiole. The value of electron microscopy in assessing such tumors is emphasized.", "contents": "Bronchiolo-alveolar carcinoma: a Clara cell tumor? The cell of origin, and indeed the very existence, of bronchiolo-alveolar carcinoma have long been the subject of debate. Published cases have demonstrated the presence of type II pneumocytes in some tumors, while others have been composed of mucus-secreting bronchiolar cells. A case of bronchiolo-alveolar carcinoma is presented in which the ultrastructure indicates an origin from Clara cells, but in which some cells contain polymorphous and lamellar bodies, It is concluded that bronchiolo-alveolar carcinoma is a primary lung tumor derived from the terminal airways and in the majority of cases from the bronchiole. The value of electron microscopy in assessing such tumors is emphasized."}
{"id": "PMID:200335", "title": "Studies of the tumorigenic effect of two goitrogens.", "content": "The nature of tumors appearing in the thyroid gland and in the lungs of mice fed two standard goitrogenic drugs (MTU and MII) has been studied. These tumors have been considered malignant on the basis of their morphological appearance and their occurrence in abnormal locations. Some investigatiors, however, have questioned that they are actually malignant. The present results indicate that these tumors are most likely not malignant even if it is shown that the pulmonary nodules are of thyroid origin. The thyroid adenomas disappear once the goitrogen is withdrawn, but thryoid enlargement pesists, and event 6 months after discontinuation of the goitrogenic treatment , pulmonary nodules are still produced. Evidence is presented that these nodules are emoli from hyperplastic thyroid tissue and not tumors.", "contents": "Studies of the tumorigenic effect of two goitrogens. The nature of tumors appearing in the thyroid gland and in the lungs of mice fed two standard goitrogenic drugs (MTU and MII) has been studied. These tumors have been considered malignant on the basis of their morphological appearance and their occurrence in abnormal locations. Some investigatiors, however, have questioned that they are actually malignant. The present results indicate that these tumors are most likely not malignant even if it is shown that the pulmonary nodules are of thyroid origin. The thyroid adenomas disappear once the goitrogen is withdrawn, but thryoid enlargement pesists, and event 6 months after discontinuation of the goitrogenic treatment , pulmonary nodules are still produced. Evidence is presented that these nodules are emoli from hyperplastic thyroid tissue and not tumors."}
{"id": "PMID:200336", "title": "Glycogen-rich Clara cell-type bronchiolo-alveolar carcinoma: light and electron microscopic study.", "content": "A clear cell type of bronchiolo-alveolar carcinoma removed from the lung of a 63-year-old man was studied by light and electron microscopy. The tumor was composed exclusively of Clara cells identified by the presence of secretory granules, an abundance of granular endoplasmic reticulum, a moderate number of mitochondria and prominent Golgi complexes. The tumor cells were tall columnar and had clear cytoplasm due to the presence of large pools of intracytoplasmic glycogen. This feature has not heretofore been described. Ultrastructural features distinguishing this tumor from benign clear cell tumors of the lung and clear cell carcinomas of the kidney are described.", "contents": "Glycogen-rich Clara cell-type bronchiolo-alveolar carcinoma: light and electron microscopic study. A clear cell type of bronchiolo-alveolar carcinoma removed from the lung of a 63-year-old man was studied by light and electron microscopy. The tumor was composed exclusively of Clara cells identified by the presence of secretory granules, an abundance of granular endoplasmic reticulum, a moderate number of mitochondria and prominent Golgi complexes. The tumor cells were tall columnar and had clear cytoplasm due to the presence of large pools of intracytoplasmic glycogen. This feature has not heretofore been described. Ultrastructural features distinguishing this tumor from benign clear cell tumors of the lung and clear cell carcinomas of the kidney are described."}
{"id": "PMID:200337", "title": "M\u00fcllerian adenosarcoma of the uterus: an ultrastructural study of four cases.", "content": "Four cases of uterine m\u00fcllerian adenosarcoma, a distinctive form of mixed m\u00fcllerian tumor, were studied by light and electron microscopy. All tumors showed the characteristic histologic pattern of benign neoplastic glands within sarcomatous stroma. Ultrastructurally, both mesenchymal and epithelial cells were seen. The mesenchymal cells showed some features of endometrial stromal cells, including the presence of intracytoplasmic collagen fibers. The epithelial cells formed glands, which resembled benign endometrial glands and were separated from the stroma by a well-defined basal lamina. No transitional cells between the epithelial and mesenchymal cells were seen. The ultrastructural features of these tumors suggest that the sarcomatous portion is of endometrial stromal origin. The glandular portion may arise, along with the stroma, from multipotential stem cells, or the glands may be non-neoplastic entrapped endometrial glands stimulated by the stroma and thus appearing to form an integral part of the tumor.", "contents": "M\u00fcllerian adenosarcoma of the uterus: an ultrastructural study of four cases. Four cases of uterine m\u00fcllerian adenosarcoma, a distinctive form of mixed m\u00fcllerian tumor, were studied by light and electron microscopy. All tumors showed the characteristic histologic pattern of benign neoplastic glands within sarcomatous stroma. Ultrastructurally, both mesenchymal and epithelial cells were seen. The mesenchymal cells showed some features of endometrial stromal cells, including the presence of intracytoplasmic collagen fibers. The epithelial cells formed glands, which resembled benign endometrial glands and were separated from the stroma by a well-defined basal lamina. No transitional cells between the epithelial and mesenchymal cells were seen. The ultrastructural features of these tumors suggest that the sarcomatous portion is of endometrial stromal origin. The glandular portion may arise, along with the stroma, from multipotential stem cells, or the glands may be non-neoplastic entrapped endometrial glands stimulated by the stroma and thus appearing to form an integral part of the tumor."}
{"id": "PMID:200338", "title": "Nasopharyngeal cancer in patients under the age of thirty years.", "content": "There is evidence that patients under 30 years of age with nasopharyngeal cancer present a somewhat different form of disease than patients of the older age group. Serum immunologic reactivity in the former was quantitatively different. Histologically, tumors in the younger age group are always of the undifferentiated type, and clinically, the disease is aggressive, characterized by frequent bone and lung metastases. The lymphatic spread into the mediastinum is accompanied by a paraneoplastic syndrome consisting of finger clubbing and hypertrophic osteoarthropathy, which is reversible after successful therapy. High rates of recovery have been obtained, even in the presence of advanced disease or metastases. This warrants a radical and persistent radiotherapeutic and or chemotherapeutic approach.", "contents": "Nasopharyngeal cancer in patients under the age of thirty years. There is evidence that patients under 30 years of age with nasopharyngeal cancer present a somewhat different form of disease than patients of the older age group. Serum immunologic reactivity in the former was quantitatively different. Histologically, tumors in the younger age group are always of the undifferentiated type, and clinically, the disease is aggressive, characterized by frequent bone and lung metastases. The lymphatic spread into the mediastinum is accompanied by a paraneoplastic syndrome consisting of finger clubbing and hypertrophic osteoarthropathy, which is reversible after successful therapy. High rates of recovery have been obtained, even in the presence of advanced disease or metastases. This warrants a radical and persistent radiotherapeutic and or chemotherapeutic approach."}
{"id": "PMID:200339", "title": "Progression of intraepithelial Paget's disease of the vulva to invasive carcinoma.", "content": "Sequential progression from intraepithelial Paget's disease of the vulva to invasive carcinoma after an interval of 10.8 years is documented in this report. Infiltration of the dermis with permeation of lymphatics and metastasis to regional lymph nodes are believed to have resulted directly from foci of intraepidermal Paget's cells that persisted after a simple vulvectomy. No underlying primary sweat gland carcinoma was present. Hence, this case establishes the invasive potential of intraepithelial vulvar Paget's disease and substantiates the notion that it is indeed a type of carcinoma in situ.", "contents": "Progression of intraepithelial Paget's disease of the vulva to invasive carcinoma. Sequential progression from intraepithelial Paget's disease of the vulva to invasive carcinoma after an interval of 10.8 years is documented in this report. Infiltration of the dermis with permeation of lymphatics and metastasis to regional lymph nodes are believed to have resulted directly from foci of intraepidermal Paget's cells that persisted after a simple vulvectomy. No underlying primary sweat gland carcinoma was present. Hence, this case establishes the invasive potential of intraepithelial vulvar Paget's disease and substantiates the notion that it is indeed a type of carcinoma in situ."}
{"id": "PMID:200340", "title": "Inhibits of of colon carcinogenesis.", "content": "Disulfiram (tetraethylthiuram disulfide, Antabuse) and sodium diethyldithiocarbamate, when added to the diet, inhibit 1,2-dimethylhydrazine (DMH)-induced neoplasia of the large bowel in female CF1 mice. Ethylene bis(dithiocarbamato)manganese (Maneb) and bis(ethylxanthogen), two pesticides with structural similarities to disulfiram, produce comparable inhibition of DHM. In other work, disulfiram was found to inhibit the carcinogenic effect of azoxymethane (AOM) on the large bowel. Under comparable conditions the inhibition of AOM was considerably less than that obtained with DMH as the carcinogen. The data suggest that disulfiram inhibits DMH metabolism at more than one oxidative step.", "contents": "Inhibits of of colon carcinogenesis. Disulfiram (tetraethylthiuram disulfide, Antabuse) and sodium diethyldithiocarbamate, when added to the diet, inhibit 1,2-dimethylhydrazine (DMH)-induced neoplasia of the large bowel in female CF1 mice. Ethylene bis(dithiocarbamato)manganese (Maneb) and bis(ethylxanthogen), two pesticides with structural similarities to disulfiram, produce comparable inhibition of DHM. In other work, disulfiram was found to inhibit the carcinogenic effect of azoxymethane (AOM) on the large bowel. Under comparable conditions the inhibition of AOM was considerably less than that obtained with DMH as the carcinogen. The data suggest that disulfiram inhibits DMH metabolism at more than one oxidative step."}
{"id": "PMID:200341", "title": "Investigations into the metabolism and mode of action of the colon carcinogens 1,2-dimethylhydrazine and azoxymethane.", "content": "Colon cancer can be induced reliably in rodents with 1,2-dimethylhydrazine and azoxymethane (AOM). Our studies deal with the mode of action of these compounds and their organotropism. A partial summary of our previous work on the metabolism of 1,2-dimethylhydrazine and its inhibition by disulfiram, carbon disulfide and other thiono-sulfur compounds is presented. On-going studies with AOM-14C indicate that in male F-344 rats, this carcinogen is rapidly metabolized to 14CO2 (37%, 48 hours), and to methylazoxymethanol-14C (MAM) (0.6--1%), which, along with other metabolites, appears in the urine. Pretreatment of rats with phenobarbital or chyrsene increased exhaled 14CO2 to 53% and 65%, respectively. Pretreatment with disulfiram or CS2 causes a complete, although transient, inhibition of exhaled 14CO2, decreases urinary MAM, and increases significantly the levels of unmetabolized AOM in the exhaled air and in urine. Thus, phenobarbital and chrysene appear to stimulate, while disulfiram and CS2 appear to inhibit, the metabolism of AOM. In vitro hydroxylation of AOM to MAM was demonstrated with rat liver homogenates and microsomal fractions. A hypothetical scheme for the endogenous formation of AOM is presented.", "contents": "Investigations into the metabolism and mode of action of the colon carcinogens 1,2-dimethylhydrazine and azoxymethane. Colon cancer can be induced reliably in rodents with 1,2-dimethylhydrazine and azoxymethane (AOM). Our studies deal with the mode of action of these compounds and their organotropism. A partial summary of our previous work on the metabolism of 1,2-dimethylhydrazine and its inhibition by disulfiram, carbon disulfide and other thiono-sulfur compounds is presented. On-going studies with AOM-14C indicate that in male F-344 rats, this carcinogen is rapidly metabolized to 14CO2 (37%, 48 hours), and to methylazoxymethanol-14C (MAM) (0.6--1%), which, along with other metabolites, appears in the urine. Pretreatment of rats with phenobarbital or chyrsene increased exhaled 14CO2 to 53% and 65%, respectively. Pretreatment with disulfiram or CS2 causes a complete, although transient, inhibition of exhaled 14CO2, decreases urinary MAM, and increases significantly the levels of unmetabolized AOM in the exhaled air and in urine. Thus, phenobarbital and chrysene appear to stimulate, while disulfiram and CS2 appear to inhibit, the metabolism of AOM. In vitro hydroxylation of AOM to MAM was demonstrated with rat liver homogenates and microsomal fractions. A hypothetical scheme for the endogenous formation of AOM is presented."}
{"id": "PMID:200342", "title": "Colorectal carcinoma in adolescents implications regarding etiology.", "content": "Between October, 1974 and December, 1976, 13 adolescent patients with far-advanced, poorly differentiated colorectal carcinoma had been referred to a pediatric cancer center. All patients received chemotherapy with vincristine, methyl-CCNU and 5-fluorouracil. Five of 13 patients are living, one of whom remains disease-free after 12 months of chemotherapy. Four of the patients were from urban areas and nine from rural areas. One of four from urban areas had intimate exposure to chemicals used in the production of cotton and soy beans. Eight of nine patients from rural areas also had exposure to farm or agricultural chemicals, and three of these patients were intimately involved with the spraying operations. Suggestions regarding etiology and causative factors for the development of carcinoma of the colon in adults have previously been advanced. Results of these studies suggest that alternate etiologies must be suggested for adolescent colorectal carcinoma.", "contents": "Colorectal carcinoma in adolescents implications regarding etiology. Between October, 1974 and December, 1976, 13 adolescent patients with far-advanced, poorly differentiated colorectal carcinoma had been referred to a pediatric cancer center. All patients received chemotherapy with vincristine, methyl-CCNU and 5-fluorouracil. Five of 13 patients are living, one of whom remains disease-free after 12 months of chemotherapy. Four of the patients were from urban areas and nine from rural areas. One of four from urban areas had intimate exposure to chemicals used in the production of cotton and soy beans. Eight of nine patients from rural areas also had exposure to farm or agricultural chemicals, and three of these patients were intimately involved with the spraying operations. Suggestions regarding etiology and causative factors for the development of carcinoma of the colon in adults have previously been advanced. Results of these studies suggest that alternate etiologies must be suggested for adolescent colorectal carcinoma."}
{"id": "PMID:200343", "title": "Overview: molecular changes associated with large bowel cancer and their potential as markers and chemotherapeutic agents.", "content": "The search for molecular changes that may be diagnostic of malignancy in the colonic epithelium is complicated by the diversity of cell types and complex cell kinetics of a tissue in which most of the cells are destined to leave within hours or days. Methods for cell separation and nuclear fractionation now permit biochemical studies of those cells that retain or regain the capacity for DNA synthesis and that are likely to include the transformed cell population. Among the changes associated with malignant transformation to be described are alterations in nuclear protein composition and metabolism, qualitative and quantitative differences in adenosine deaminase activities, activation of the guanylate/cyclic GMP system, and modification of both DNA and chromosomal proteins by alkylating carcinogens. DNA modification to produce O6-methylguanine correlates well with the incidence of tumor induction by methylazoxymethanol. Modifications of chromosomal proteins to produce methylated derivatives of lysine and arginine have been observed after the administration of 1,2-dimethylhydrazine. Such changes are likely to lead to aberrant interactions between DNA and regulatory elements in chromatin, and may not be subject to repair.", "contents": "Overview: molecular changes associated with large bowel cancer and their potential as markers and chemotherapeutic agents. The search for molecular changes that may be diagnostic of malignancy in the colonic epithelium is complicated by the diversity of cell types and complex cell kinetics of a tissue in which most of the cells are destined to leave within hours or days. Methods for cell separation and nuclear fractionation now permit biochemical studies of those cells that retain or regain the capacity for DNA synthesis and that are likely to include the transformed cell population. Among the changes associated with malignant transformation to be described are alterations in nuclear protein composition and metabolism, qualitative and quantitative differences in adenosine deaminase activities, activation of the guanylate/cyclic GMP system, and modification of both DNA and chromosomal proteins by alkylating carcinogens. DNA modification to produce O6-methylguanine correlates well with the incidence of tumor induction by methylazoxymethanol. Modifications of chromosomal proteins to produce methylated derivatives of lysine and arginine have been observed after the administration of 1,2-dimethylhydrazine. Such changes are likely to lead to aberrant interactions between DNA and regulatory elements in chromatin, and may not be subject to repair."}
{"id": "PMID:200344", "title": "Selective toxicity induced by picolinic acid in simian virus 40-transformed cells in tissue culture.", "content": "When cultured normal and SV40-transformed normal rat kidney and BALB/3T3 cells were exposed to picolinic acid, cell proliferation ceases. Most of the normal cells remained in a quiescent G1 (G0) state and viable for prolonged periods of time. In contrast, SV40-transformed cells progressed to the S and G2 phases of the cell cycle and remained viable only up to 90 to 120 hr. Then, most of the cells began to die. However, a very small fraction of the cell population (approximately 0.01 percent) developed into variants resistant to picolinic acid. Prevention of development of variants, and therefore destruction of all transformed cells, was obtained by addition of glycerol to picolinic acid-treated cells. Untransformed cells were unaffected by the same treatment. These results suggest that differential tumor toxicity should be feasible.", "contents": "Selective toxicity induced by picolinic acid in simian virus 40-transformed cells in tissue culture. When cultured normal and SV40-transformed normal rat kidney and BALB/3T3 cells were exposed to picolinic acid, cell proliferation ceases. Most of the normal cells remained in a quiescent G1 (G0) state and viable for prolonged periods of time. In contrast, SV40-transformed cells progressed to the S and G2 phases of the cell cycle and remained viable only up to 90 to 120 hr. Then, most of the cells began to die. However, a very small fraction of the cell population (approximately 0.01 percent) developed into variants resistant to picolinic acid. Prevention of development of variants, and therefore destruction of all transformed cells, was obtained by addition of glycerol to picolinic acid-treated cells. Untransformed cells were unaffected by the same treatment. These results suggest that differential tumor toxicity should be feasible."}
{"id": "PMID:200346", "title": "Radioimmunoassay for glycoprotein gp47 of murine mammary tumor virus in organs and serum of mice and search for related antigens in human sera.", "content": "Murine mammary tumor virus main glycoprotein (gp47), prepared by diethylaminoethyl cellulose and hydroxyapatite chromatography of detergent-mercaptoethanol-KCI-disrupted virion, was used as labeled antigen in a highly specific and reproducible radioimmunoassay. Seven other (glyco) proteins of the virus were antigenically distinct from gp47. Serum and organs of unifected C57BL mice did not contain gp47, but sera of infected Swiss and RIII mice did contain the antigen. Despite the high content in the mammary gland, the level of gp47 in other organs was identical in male and female mice. The titer of gp47 in serum was high in tumor-bearing females, but it varied with the mouse strain. Anti-gp47 immunoglobulins could not be detected. The investigation included 314 human sera (107 normal, 65 benign mastopathy, 89 breast vancer, and 53 digestive cancer). None contained an antigen related to gp47. One of 20 human mammary cyst fluids was positive.", "contents": "Radioimmunoassay for glycoprotein gp47 of murine mammary tumor virus in organs and serum of mice and search for related antigens in human sera. Murine mammary tumor virus main glycoprotein (gp47), prepared by diethylaminoethyl cellulose and hydroxyapatite chromatography of detergent-mercaptoethanol-KCI-disrupted virion, was used as labeled antigen in a highly specific and reproducible radioimmunoassay. Seven other (glyco) proteins of the virus were antigenically distinct from gp47. Serum and organs of unifected C57BL mice did not contain gp47, but sera of infected Swiss and RIII mice did contain the antigen. Despite the high content in the mammary gland, the level of gp47 in other organs was identical in male and female mice. The titer of gp47 in serum was high in tumor-bearing females, but it varied with the mouse strain. Anti-gp47 immunoglobulins could not be detected. The investigation included 314 human sera (107 normal, 65 benign mastopathy, 89 breast vancer, and 53 digestive cancer). None contained an antigen related to gp47. One of 20 human mammary cyst fluids was positive."}
{"id": "PMID:200347", "title": "Membranous effects on adenosine triphosphatase activities of mitochondria from rat liver and Morris hepatoma 3924A.", "content": "Adenosine triphosphatase (ATPase) activities of sonically prepared submitochondrial particles of rat liver and Morris Hepatoma 3924A were compared as a function of changes in temperature. On Arrhenius plots, a discontinuity at 18 degrees was observed for the rat liver mitochondrial ATPase, while the hepatoma mitochondrial ATPase revealed a discontinuity at 20.4 degrees. Values for energy of activation of the rat liver and hepatoma mitochondrial ATPases were comparable below the break (34.5 and 35.5 kcal/mole, respectively) and above the break (11.6 and 9.2 kcal/mole, respectively). Solubilization of the mitochondrial membrances with Triton X-100 resulted in constant and similar values of energy of activation for the ATPases Km values of hepatoma and rat liver mitochondrial ATPases for adenosine triphosphate were similar in both the membrane-bound and solubilized states. The lack of uncoupler-stimulated ATPase activity in hepatoma mitochondria is apparently not due to membranous effects on the affinity of the ATPase for adenosine triphosphate.", "contents": "Membranous effects on adenosine triphosphatase activities of mitochondria from rat liver and Morris hepatoma 3924A. Adenosine triphosphatase (ATPase) activities of sonically prepared submitochondrial particles of rat liver and Morris Hepatoma 3924A were compared as a function of changes in temperature. On Arrhenius plots, a discontinuity at 18 degrees was observed for the rat liver mitochondrial ATPase, while the hepatoma mitochondrial ATPase revealed a discontinuity at 20.4 degrees. Values for energy of activation of the rat liver and hepatoma mitochondrial ATPases were comparable below the break (34.5 and 35.5 kcal/mole, respectively) and above the break (11.6 and 9.2 kcal/mole, respectively). Solubilization of the mitochondrial membrances with Triton X-100 resulted in constant and similar values of energy of activation for the ATPases Km values of hepatoma and rat liver mitochondrial ATPases for adenosine triphosphate were similar in both the membrane-bound and solubilized states. The lack of uncoupler-stimulated ATPase activity in hepatoma mitochondria is apparently not due to membranous effects on the affinity of the ATPase for adenosine triphosphate."}
{"id": "PMID:200348", "title": "Scanning electron microscopy of the surfaces of hamster embryo cells transformed by herpes simplex virus.", "content": "The surfaces of normal hamster embryo fibroblast (HEF) cells were examined by scanning electron microscopy. Surface characteristics of HEF cells were compared to those of cells derived from a primary tumor induced in hamsters following s.c. inoculation of herpes simplex virus type 1-transformed HEF cells (14-012-8-1) and to the surfaces of cells derived from a metastatic tumor to the lung induced by the same cells. The most obvious difference in the surface characteristics of the examined cells was the morphology of the microvilli. In the few HEF cells that possessed microvilli, the distribution was uneven, and the lengths of the microvilli and the filopodia were variable. However, the surfaces of both tumor cell lines showed large numbers of microvilli which were evenly distributed over the surface of the cells, giving an almost \"hairy\" appearance. Long filopodia were occasionally observed on the surface of the primary tumor cell line and on the cell line derived from the metastatic tumor. Ruffles and blebs were occasionally observed on HEF cells and on the primary tumor cells but were not seen on the cells of the metastatic tumor.", "contents": "Scanning electron microscopy of the surfaces of hamster embryo cells transformed by herpes simplex virus. The surfaces of normal hamster embryo fibroblast (HEF) cells were examined by scanning electron microscopy. Surface characteristics of HEF cells were compared to those of cells derived from a primary tumor induced in hamsters following s.c. inoculation of herpes simplex virus type 1-transformed HEF cells (14-012-8-1) and to the surfaces of cells derived from a metastatic tumor to the lung induced by the same cells. The most obvious difference in the surface characteristics of the examined cells was the morphology of the microvilli. In the few HEF cells that possessed microvilli, the distribution was uneven, and the lengths of the microvilli and the filopodia were variable. However, the surfaces of both tumor cell lines showed large numbers of microvilli which were evenly distributed over the surface of the cells, giving an almost \"hairy\" appearance. Long filopodia were occasionally observed on the surface of the primary tumor cell line and on the cell line derived from the metastatic tumor. Ruffles and blebs were occasionally observed on HEF cells and on the primary tumor cells but were not seen on the cells of the metastatic tumor."}
{"id": "PMID:200349", "title": "Tumor-associated immunoglobulins in pulmonary carcinoma.", "content": "In view of the uncertainty of location and significance of immunoglobulin in tumors found by elution or rosette formation (as reported in the literature), the presence of IgG, IgM, and IgA in human carcinoma of the lung was studied by means of the peroxidase-antiperoxidase method. Surgically obtained specimens from patients with known survival times were used in this study. Membranous as well as cytoplasmic location of IgG was demonstrated more frequently than was that of IgA or IgM. The number of tumor cells carrying immunoglobulin varied greatly, even within a given case. Albumin could be demonstrated in tumor cells in 10 of 20 specimens, but there was poor correlation with immunoglobuin. In some instances, only the necrotic part of the tumor or the stroma was immunoreactive. The results are discussed and suggest that Fc receptors are not involved in the binding of immunoglobin by pulmonary carcinoma cells.", "contents": "Tumor-associated immunoglobulins in pulmonary carcinoma. In view of the uncertainty of location and significance of immunoglobulin in tumors found by elution or rosette formation (as reported in the literature), the presence of IgG, IgM, and IgA in human carcinoma of the lung was studied by means of the peroxidase-antiperoxidase method. Surgically obtained specimens from patients with known survival times were used in this study. Membranous as well as cytoplasmic location of IgG was demonstrated more frequently than was that of IgA or IgM. The number of tumor cells carrying immunoglobulin varied greatly, even within a given case. Albumin could be demonstrated in tumor cells in 10 of 20 specimens, but there was poor correlation with immunoglobuin. In some instances, only the necrotic part of the tumor or the stroma was immunoreactive. The results are discussed and suggest that Fc receptors are not involved in the binding of immunoglobin by pulmonary carcinoma cells."}
{"id": "PMID:200350", "title": "Long-term effects of prenatal and neonatal administration of 5beta-dihydrotestosterone on normal and neoplastic mammary development in mice.", "content": "The long-term effects on mammary glands of 5beta-dihydrotestosterone, considered to be biologically inactive, were studied in female SHN mice with mammary tumor, virus. 5beta-Dihydrotestosterone was adminstered to mothers for 4 days from Day 12 to Day 15 of pregnancy (prenatal treatment) and to pups for 5 days of postnatal life (neonatal treatment) at daily doses of 1 mg and 200 mug, respectively. Neonatal treatment resulted in marked stimulation of spontaneous mammary tumorigenesis; all neonatally treated mice had palpable mammary tumors by 6.2 months of age, when mammary tumor incidences in the control mice and in mice treated prenatally with 5beta-dihydrotestosterone were 21.1 and 6.3 percent, respectively. Furthermore, neonatal treatment promoted normal and preneoplastic mammary growth and pituitary prolactin secretion and induced ovarian anovulatory syndrome in all mice. Prenatal treatment also increased the number of mammary hyperplastic alveolar nodules and induced an delayed anovulatory syndrome. These results have demonstrated that perinatal treatment with 5beta-dihydrotestosterone can induce such irreversible changes in the mammary glands, pituitary gland, ovaries, and genital tracts as those seen with other biologically active steroid hormones.", "contents": "Long-term effects of prenatal and neonatal administration of 5beta-dihydrotestosterone on normal and neoplastic mammary development in mice. The long-term effects on mammary glands of 5beta-dihydrotestosterone, considered to be biologically inactive, were studied in female SHN mice with mammary tumor, virus. 5beta-Dihydrotestosterone was adminstered to mothers for 4 days from Day 12 to Day 15 of pregnancy (prenatal treatment) and to pups for 5 days of postnatal life (neonatal treatment) at daily doses of 1 mg and 200 mug, respectively. Neonatal treatment resulted in marked stimulation of spontaneous mammary tumorigenesis; all neonatally treated mice had palpable mammary tumors by 6.2 months of age, when mammary tumor incidences in the control mice and in mice treated prenatally with 5beta-dihydrotestosterone were 21.1 and 6.3 percent, respectively. Furthermore, neonatal treatment promoted normal and preneoplastic mammary growth and pituitary prolactin secretion and induced ovarian anovulatory syndrome in all mice. Prenatal treatment also increased the number of mammary hyperplastic alveolar nodules and induced an delayed anovulatory syndrome. These results have demonstrated that perinatal treatment with 5beta-dihydrotestosterone can induce such irreversible changes in the mammary glands, pituitary gland, ovaries, and genital tracts as those seen with other biologically active steroid hormones."}
{"id": "PMID:200351", "title": "alpha-Lactalbumin levels in human mammary tumors, sera, and mammary cell culture lines.", "content": "Antiserum to purified human alpha-lactalbumin was produced in rabbits and used to develop a radioimmunoassay capable of detecting 0.1 ng of alpha-lactalbumin per ml of sample. Human breast diseases were analyzed for alpha-lactalbumin levels. A high percentage of breast carcinomas contained varying levels of alpha-lactalbumin. Lymph node metastases from primary carcinomas that synthesized alpha-lactalbumin also contained it. Analysis of serum from breast cancer patients indicated that approximately 25 percent had measurable levels of alpha-lactalbumin before surgery, but no alpha-lactalbumin was found in postsurgery sera. alpha-Lactalbumin was not detected in the urine of early lactational women, although it was present in the sera. Human cell culture lines derived from pleural effusions of mammary carcinomas contained little, if any, alpha-lactalbumin. Other human cell lines derived from mammary carcinomas and grown as solid tumors in athymic mice did not contain measurable levels of alpha-lactalbumin.", "contents": "alpha-Lactalbumin levels in human mammary tumors, sera, and mammary cell culture lines. Antiserum to purified human alpha-lactalbumin was produced in rabbits and used to develop a radioimmunoassay capable of detecting 0.1 ng of alpha-lactalbumin per ml of sample. Human breast diseases were analyzed for alpha-lactalbumin levels. A high percentage of breast carcinomas contained varying levels of alpha-lactalbumin. Lymph node metastases from primary carcinomas that synthesized alpha-lactalbumin also contained it. Analysis of serum from breast cancer patients indicated that approximately 25 percent had measurable levels of alpha-lactalbumin before surgery, but no alpha-lactalbumin was found in postsurgery sera. alpha-Lactalbumin was not detected in the urine of early lactational women, although it was present in the sera. Human cell culture lines derived from pleural effusions of mammary carcinomas contained little, if any, alpha-lactalbumin. Other human cell lines derived from mammary carcinomas and grown as solid tumors in athymic mice did not contain measurable levels of alpha-lactalbumin."}
{"id": "PMID:200353", "title": "Inhibition of concanavalin A stimulation of feline lymphocytes by inactivated feline leukemia virus.", "content": "In a lymphocyte blast transformation assay, the response of feline lymphocytes to concanavalin A was suppressed 20 to 65 percent in the presence of inactivated feline leukemia virus. The decrease was not due to viral cytotoxicity, as determined by trypan blue viability counts, nor was the virus binding the concanavalin A and interfering with its mitogenic stimulation. The virus may be biochemically repressive in itself, interfering with cell-mediated immunity within the feline system.", "contents": "Inhibition of concanavalin A stimulation of feline lymphocytes by inactivated feline leukemia virus. In a lymphocyte blast transformation assay, the response of feline lymphocytes to concanavalin A was suppressed 20 to 65 percent in the presence of inactivated feline leukemia virus. The decrease was not due to viral cytotoxicity, as determined by trypan blue viability counts, nor was the virus binding the concanavalin A and interfering with its mitogenic stimulation. The virus may be biochemically repressive in itself, interfering with cell-mediated immunity within the feline system."}
{"id": "PMID:200355", "title": "Biological characterization of an Epstein-Barr nuclear antigen-positive American Burkitt's tumor-derived cell line.", "content": "Two distinct cultures derived from a lymphoid cell line designated NAB were characterized immunologically, morphologically, and cytogenetically. Both cultures were positive for Epstein-Barr nuclear antigen. NAB I cultures were negative for virus capsid antigen and early antigen and were not affected by treatment with 5-iododeoxyurdine. NAB II cultures were positive for virus capsid antigen and early antigen, which increased with 5-iododeoxyuridine treatment. Both cultures were superinfected with virus prepared from P3HR-1 cells. Cell-free virus concentrates prepared from both cultures were inactive for transformation and infectivity. NAB I and NAB II cells were lymphoid as determined by light and electron microscopy. NAB II cells showed morphological alterations characteristic of herpes infection. 5-iododeoxyuridine-treated cells from both cultures revealed ultrastructural characteristics of cells infected with herpes-viruses but without particles. In addition, the induction of tubuloreticular structures within the endoplasmic reticulum was observed. Cytogenetic analysis of both cultures revealed a rearranged chromosome 14 and several other chromosome aberrations, three of which may be used as a reliable means of identifying NAB cultures.", "contents": "Biological characterization of an Epstein-Barr nuclear antigen-positive American Burkitt's tumor-derived cell line. Two distinct cultures derived from a lymphoid cell line designated NAB were characterized immunologically, morphologically, and cytogenetically. Both cultures were positive for Epstein-Barr nuclear antigen. NAB I cultures were negative for virus capsid antigen and early antigen and were not affected by treatment with 5-iododeoxyurdine. NAB II cultures were positive for virus capsid antigen and early antigen, which increased with 5-iododeoxyuridine treatment. Both cultures were superinfected with virus prepared from P3HR-1 cells. Cell-free virus concentrates prepared from both cultures were inactive for transformation and infectivity. NAB I and NAB II cells were lymphoid as determined by light and electron microscopy. NAB II cells showed morphological alterations characteristic of herpes infection. 5-iododeoxyuridine-treated cells from both cultures revealed ultrastructural characteristics of cells infected with herpes-viruses but without particles. In addition, the induction of tubuloreticular structures within the endoplasmic reticulum was observed. Cytogenetic analysis of both cultures revealed a rearranged chromosome 14 and several other chromosome aberrations, three of which may be used as a reliable means of identifying NAB cultures."}
{"id": "PMID:200357", "title": "Role of radiation therapy in combination with chemotherapy in extensive oat cell cancer of the lung: a randomized study.", "content": "After 3 months of chemotherapy with procarbazine, vincristine, cyclophosphamide, and CCNU, patients with extensive oat cell carcinoma of the lung were randomly allocated to receive 3000 rads of involved-field irradiation and further chemotherapy or to continue with chemotherapy only. In addition, all patients received 3000 rads of prophylactic whole-brain irradiation. The addition of involved-field radiation, as given in this trial, not only failed to improve survival but was unable to alter the pattern of sites of initial relapse. There were no cases of extension to the brain in 31 consecutive patients who received prophylactic whole-brain irradiation. This was in strong contrast to a preceding trial in which six cases of brain extension occurred among 19 patients who did not receive prophylactic whole-brain irradiation.", "contents": "Role of radiation therapy in combination with chemotherapy in extensive oat cell cancer of the lung: a randomized study. After 3 months of chemotherapy with procarbazine, vincristine, cyclophosphamide, and CCNU, patients with extensive oat cell carcinoma of the lung were randomly allocated to receive 3000 rads of involved-field irradiation and further chemotherapy or to continue with chemotherapy only. In addition, all patients received 3000 rads of prophylactic whole-brain irradiation. The addition of involved-field radiation, as given in this trial, not only failed to improve survival but was unable to alter the pattern of sites of initial relapse. There were no cases of extension to the brain in 31 consecutive patients who received prophylactic whole-brain irradiation. This was in strong contrast to a preceding trial in which six cases of brain extension occurred among 19 patients who did not receive prophylactic whole-brain irradiation."}
{"id": "PMID:200361", "title": "Autoradiographic studies of 3H-dexamethasone uptake by immunocytochemically characterized cells of the rat pituitary.", "content": "3H-Dexamethasone (10 microgram/kg) was injected intravenously in adrenalectomized rats and after survival times of 5, 30, 60, and 180 min its uptake within the pituitary was studied by autoradiography. Radioactivity was concentrated in cell nuclei in the pars nervosa and pars distalis. Within the pars intermedia, only cells of the marginal zone were labeled. In the pars distalis, some cells showed a weak nuclear accumulation of radioactivity as early as 5 min after injection. The tissue radioactivity was nearly maximal at 5 min, and the proportion of radioactivity in nuclei reached a maximum of 60-70% by 30 min. In competition experiments, non-radioactive steroids (1 mg/kg) were injected 5 min before 3H-dexamethasone and sacrifice was 30 min later. Dexamethasone markedly diminished the nuclear accumulation in the pars distalis, but corticosterone and progesterone did not. In the pars nervosa, corticosterone and progesterone competed for nuclear uptake of 3H-dexamethasone, although less effectively than dexamethasone itself. Different cell types in the pars distalis were characterized by treating autoradiograms with an immuno-peroxidase bridge procedure. Cells treated with anti-ACTH 17-39 had the greatest nuclear concentration of radioactivity, and those stained with anti-TSH were least heavily labeled. Cells treated with antisera to GH, PRL, and hCG were moderately labeled.", "contents": "Autoradiographic studies of 3H-dexamethasone uptake by immunocytochemically characterized cells of the rat pituitary. 3H-Dexamethasone (10 microgram/kg) was injected intravenously in adrenalectomized rats and after survival times of 5, 30, 60, and 180 min its uptake within the pituitary was studied by autoradiography. Radioactivity was concentrated in cell nuclei in the pars nervosa and pars distalis. Within the pars intermedia, only cells of the marginal zone were labeled. In the pars distalis, some cells showed a weak nuclear accumulation of radioactivity as early as 5 min after injection. The tissue radioactivity was nearly maximal at 5 min, and the proportion of radioactivity in nuclei reached a maximum of 60-70% by 30 min. In competition experiments, non-radioactive steroids (1 mg/kg) were injected 5 min before 3H-dexamethasone and sacrifice was 30 min later. Dexamethasone markedly diminished the nuclear accumulation in the pars distalis, but corticosterone and progesterone did not. In the pars nervosa, corticosterone and progesterone competed for nuclear uptake of 3H-dexamethasone, although less effectively than dexamethasone itself. Different cell types in the pars distalis were characterized by treating autoradiograms with an immuno-peroxidase bridge procedure. Cells treated with anti-ACTH 17-39 had the greatest nuclear concentration of radioactivity, and those stained with anti-TSH were least heavily labeled. Cells treated with antisera to GH, PRL, and hCG were moderately labeled."}
{"id": "PMID:200362", "title": "Filaments and rod-shaped tubulated bodies in the endothelia of anterior cerebral arteries in young rats.", "content": "Endothelia of the anterior cerebral arteries in rats aged 1 to 3 days were studied. Thin (about 50-90 A) and thick (about 100-110 A) filaments are present in the endothelia. Numerous spherical- or rod-shaped bodies, measuring approximately 0.07 to 0.3 micrometer in diameter and up to 0.6 micrometer in length occur in the endothelial cells. These bodies contain a tubular structure. The diameter of the individual tubules is about 200 A. The present observations suggest that spherical- or rod-shaped inclusions are first synthesized in the rough endoplasmic reticulum and thereafter these materials are transported into the Golgi complex for maturation. A small number of the inclusions, however, may originate directly from the rough endoplasmic reticulum and not pass through the Golgi apparatus.", "contents": "Filaments and rod-shaped tubulated bodies in the endothelia of anterior cerebral arteries in young rats. Endothelia of the anterior cerebral arteries in rats aged 1 to 3 days were studied. Thin (about 50-90 A) and thick (about 100-110 A) filaments are present in the endothelia. Numerous spherical- or rod-shaped bodies, measuring approximately 0.07 to 0.3 micrometer in diameter and up to 0.6 micrometer in length occur in the endothelial cells. These bodies contain a tubular structure. The diameter of the individual tubules is about 200 A. The present observations suggest that spherical- or rod-shaped inclusions are first synthesized in the rough endoplasmic reticulum and thereafter these materials are transported into the Golgi complex for maturation. A small number of the inclusions, however, may originate directly from the rough endoplasmic reticulum and not pass through the Golgi apparatus."}
{"id": "PMID:200363", "title": "Effect of cyproterone acetate on cells of the pars distalis of the adenohypophysis in the beagle bitch.", "content": "The effects of oral administration of 100 mg per kg per day cyproterone acetate (CPA) for four weeks on cells of the pars distalis, as revealed by the immunoperoxidase technique and chemical staining, were studied in the ovariectomized beagle bitch. For immunochemical staining antisera to the following hormones were used: canine GH, canine PRL, procine ACHT, bovine TSH beta, bovine  LH beta and human FSH beta1. The most striking effects of the treatment were an overall increase in the relative proportion of GH cells and a marked morphological indication of high secretory activity in these cells. In contrast, PRL cells were not affected significantly. In all ovariectomized control bitches a marked atrophy of the cells stained for FSH beta (FSH cells) and hypertrophy of the cells shown to contain LH beta (LH cells) were observed. FSH cells became enlarged, while LH cells appeared reduced in size by administration of CPA. In some treated bitches ACTH/MSH cells showed atrophy and regressive changes, whereas TSH cells seemed to become enlarged and were more densely arranged. These structural responses indicate that, in addition to its partial antigonadotropic properties, CPA as a synthetic progesterone derivative may stimulate GH secretion and possibly suppress CRH-ACTH activity in the ovariectomized beagle bitch.", "contents": "Effect of cyproterone acetate on cells of the pars distalis of the adenohypophysis in the beagle bitch. The effects of oral administration of 100 mg per kg per day cyproterone acetate (CPA) for four weeks on cells of the pars distalis, as revealed by the immunoperoxidase technique and chemical staining, were studied in the ovariectomized beagle bitch. For immunochemical staining antisera to the following hormones were used: canine GH, canine PRL, procine ACHT, bovine TSH beta, bovine  LH beta and human FSH beta1. The most striking effects of the treatment were an overall increase in the relative proportion of GH cells and a marked morphological indication of high secretory activity in these cells. In contrast, PRL cells were not affected significantly. In all ovariectomized control bitches a marked atrophy of the cells stained for FSH beta (FSH cells) and hypertrophy of the cells shown to contain LH beta (LH cells) were observed. FSH cells became enlarged, while LH cells appeared reduced in size by administration of CPA. In some treated bitches ACTH/MSH cells showed atrophy and regressive changes, whereas TSH cells seemed to become enlarged and were more densely arranged. These structural responses indicate that, in addition to its partial antigonadotropic properties, CPA as a synthetic progesterone derivative may stimulate GH secretion and possibly suppress CRH-ACTH activity in the ovariectomized beagle bitch."}
{"id": "PMID:200364", "title": "Autoradiographic study of the distribution of LH(HCG) receptors in the ovary of untreated and gonadotrophin-primed immature rats.", "content": "The LH(HCG) receptors in the ovaries of immature rats which were either untreated, or primed with PMSG and HCG, have been studied with a histochemical method which has proved to be as effective as when earlier used in the rat testis. This method, which consists of the topical application of 125I-HCG to picric acid-formaldehyde (PAF) fixed frozen sections followed by autoradiography, is also suitable for quantitative studies on the distribution of receptors. In the ovary of the immature 26 days old rat, the LH(HCG) receptors are localized exclusively in the interstitial and thecal tissues. After PMSG treatment many receptors appear in the granulosa of the large antral follicles. These receptors are most numerous in the outer layers of cells and least numerous in the inner. At the same time there are fewer receptors in the thecal and interstitial cells which have undergone the process of luteinization. After PMSG and HCG treatment the newly formed corpora lutea have few receptors, but these become progressively more numerous on subsequent days. It is suggested that, in the rat, the luteinization of the ovarian LH-target cells is associated with an initial decrease in the number of their LH(HCG) receptors.", "contents": "Autoradiographic study of the distribution of LH(HCG) receptors in the ovary of untreated and gonadotrophin-primed immature rats. The LH(HCG) receptors in the ovaries of immature rats which were either untreated, or primed with PMSG and HCG, have been studied with a histochemical method which has proved to be as effective as when earlier used in the rat testis. This method, which consists of the topical application of 125I-HCG to picric acid-formaldehyde (PAF) fixed frozen sections followed by autoradiography, is also suitable for quantitative studies on the distribution of receptors. In the ovary of the immature 26 days old rat, the LH(HCG) receptors are localized exclusively in the interstitial and thecal tissues. After PMSG treatment many receptors appear in the granulosa of the large antral follicles. These receptors are most numerous in the outer layers of cells and least numerous in the inner. At the same time there are fewer receptors in the thecal and interstitial cells which have undergone the process of luteinization. After PMSG and HCG treatment the newly formed corpora lutea have few receptors, but these become progressively more numerous on subsequent days. It is suggested that, in the rat, the luteinization of the ovarian LH-target cells is associated with an initial decrease in the number of their LH(HCG) receptors."}
{"id": "PMID:200365", "title": "Formaldehyde-ozone-induced fluorescence in pituitary ACTH cells: effect of adrenalectomy.", "content": "ACTH and MSH cells of the pituitary are rich in peptides with NH2-terminaltryptophan, as revealed by fluorescence histochemistry. Adrenalectomy stimulates the ACTH cells but not the MSH cells. As a result, ACTH as well as tryptophyl-peptides disappear from the ACTH cells but not from the MSH cells. It is concluded that the tryptophyl-peptides are stored together with the respective hormone in the ACTH and MSH cells and that tryptophyl-peptides in the ACTH cells are released together with the hormone.", "contents": "Formaldehyde-ozone-induced fluorescence in pituitary ACTH cells: effect of adrenalectomy. ACTH and MSH cells of the pituitary are rich in peptides with NH2-terminaltryptophan, as revealed by fluorescence histochemistry. Adrenalectomy stimulates the ACTH cells but not the MSH cells. As a result, ACTH as well as tryptophyl-peptides disappear from the ACTH cells but not from the MSH cells. It is concluded that the tryptophyl-peptides are stored together with the respective hormone in the ACTH and MSH cells and that tryptophyl-peptides in the ACTH cells are released together with the hormone."}
{"id": "PMID:200366", "title": "Comparative cellular localization of corticotropin and melanotropin in lerot adenohypophysis (Eliomys quercinus). An immunohistochemical study.", "content": "Corticotropin and melanotropin producing cells were localized in the adenohypophysis of normal Lerots by using antibodies against synthetic corticotropins (anti beta1-24 ACTH, anti alpha17-39 ACTH, anti alpha25-39 ACTH), and melanotropins (anti alpha MSH, anti beta MSH). All the anticorticotropin sera stained the same cells both in the anterior lobe and in the intermediate lobe. The anti alpha MSH serum only stained a few cells, exclusively located in the intermediate lobe. These alpha MSH cells were not stained with anticorticotropin antibodies. The anti beta MSH serum revealed all the cells stained with anticorticotropin and anti alpha MSH sera. Absorption tests showed that the 4-10 heptapeptide common to ACTH and MSH, is not responsible for the immunohistochemical staining. The staining of only some corticotrophs with the anti 4-10 ACTH serum might indicate the presence in these cells of a peptide with an accessible 4-10 site. These results are discussed.", "contents": "Comparative cellular localization of corticotropin and melanotropin in lerot adenohypophysis (Eliomys quercinus). An immunohistochemical study. Corticotropin and melanotropin producing cells were localized in the adenohypophysis of normal Lerots by using antibodies against synthetic corticotropins (anti beta1-24 ACTH, anti alpha17-39 ACTH, anti alpha25-39 ACTH), and melanotropins (anti alpha MSH, anti beta MSH). All the anticorticotropin sera stained the same cells both in the anterior lobe and in the intermediate lobe. The anti alpha MSH serum only stained a few cells, exclusively located in the intermediate lobe. These alpha MSH cells were not stained with anticorticotropin antibodies. The anti beta MSH serum revealed all the cells stained with anticorticotropin and anti alpha MSH sera. Absorption tests showed that the 4-10 heptapeptide common to ACTH and MSH, is not responsible for the immunohistochemical staining. The staining of only some corticotrophs with the anti 4-10 ACTH serum might indicate the presence in these cells of a peptide with an accessible 4-10 site. These results are discussed."}
{"id": "PMID:200367", "title": "The display of microtubules in transformed cells.", "content": "Monospecific tubulin antibodies have been used in indirect immunofluorescence microscopy on a variety of well characterized, transformed cell lines grown in tissue culture. Networks of colcemid-sensitive fibers are seen in SV40-transformed 3T3 cells, SV40-transformed rat embryo cells, HeLa cells and other transformed cell lines. In each case, greater than 90% of the cells contain visible microtubular networks, and where individual microtubules can be distinguished, they run for long distances. Documentation of these metworks is more difficult in transformed than in normal cells, because transformed cells are in general more rounded and have less well spread cytoplasm. In addition, the microtubular networks can be readily visualized in \"cytoskeletons\" of both normal and transformed cells, obtained by treatment of cells with nonionic detergents in a buffer which stabilizes microtubules in vitro. Addition of calcium to this buffer results in in situ fragmentation and destruction of the microtubular network. In view of these results, we conclude that transformed cells contain significant numbers of microtubules, and that in transformed cells, as in normal cells, microtubules are arranged in networks.", "contents": "The display of microtubules in transformed cells. Monospecific tubulin antibodies have been used in indirect immunofluorescence microscopy on a variety of well characterized, transformed cell lines grown in tissue culture. Networks of colcemid-sensitive fibers are seen in SV40-transformed 3T3 cells, SV40-transformed rat embryo cells, HeLa cells and other transformed cell lines. In each case, greater than 90% of the cells contain visible microtubular networks, and where individual microtubules can be distinguished, they run for long distances. Documentation of these metworks is more difficult in transformed than in normal cells, because transformed cells are in general more rounded and have less well spread cytoplasm. In addition, the microtubular networks can be readily visualized in \"cytoskeletons\" of both normal and transformed cells, obtained by treatment of cells with nonionic detergents in a buffer which stabilizes microtubules in vitro. Addition of calcium to this buffer results in in situ fragmentation and destruction of the microtubular network. In view of these results, we conclude that transformed cells contain significant numbers of microtubules, and that in transformed cells, as in normal cells, microtubules are arranged in networks."}
{"id": "PMID:200369", "title": "Abelson virus-transformed lymphocytes: null cells that modulate H-2.", "content": "A-MuLV-transformed lymphoid cells from Balb/c mice had the properties of null lymphocytes. They did not secrete Ig and all but one did not have detectable cell-associated Ig; one line synthesized, but did not secrete, the mu chain of IgM. The cells expressed H-2D and H-2K, but not H-21 histocompatibility antigens or theta-antigen; they had Fc receptors. Most cell lines grew to form donor cell tumors after inoculation into (Balb/c X C57B1/6)F1 mice. The tumor cells have more H-2Dd than cells passaged in vitro. Cell lines carried in vitro progressively lost H-2Dd. A line in which 5-30% of the cells were lysable by anti-H-2Dd was cloned; all eleven clones had H-2Dd (13-69% lysable) demonstrating that H-2 modulates in vitro. A clone with little H-2Dd (10-15% lysable) was tumorigenic even after treatment with anti-H-2Dd sera; at least 50% of the tumor cells were lysed by anti-H-2Dd. Thus A-MuLV-transformed lymphocytes modulate H-2 in vivo to higher levels and in vitro to lower levels.", "contents": "Abelson virus-transformed lymphocytes: null cells that modulate H-2. A-MuLV-transformed lymphoid cells from Balb/c mice had the properties of null lymphocytes. They did not secrete Ig and all but one did not have detectable cell-associated Ig; one line synthesized, but did not secrete, the mu chain of IgM. The cells expressed H-2D and H-2K, but not H-21 histocompatibility antigens or theta-antigen; they had Fc receptors. Most cell lines grew to form donor cell tumors after inoculation into (Balb/c X C57B1/6)F1 mice. The tumor cells have more H-2Dd than cells passaged in vitro. Cell lines carried in vitro progressively lost H-2Dd. A line in which 5-30% of the cells were lysable by anti-H-2Dd was cloned; all eleven clones had H-2Dd (13-69% lysable) demonstrating that H-2 modulates in vitro. A clone with little H-2Dd (10-15% lysable) was tumorigenic even after treatment with anti-H-2Dd sera; at least 50% of the tumor cells were lysed by anti-H-2Dd. Thus A-MuLV-transformed lymphocytes modulate H-2 in vivo to higher levels and in vitro to lower levels."}
{"id": "PMID:200376", "title": "Inhibition by aldehydes as a possible further mechanism for glucose-6-phosphatase inactivation during CCl4-poisoning.", "content": "Diffusable aldehydes are known to be produced during lipoperoxidative deterioration of unsaturated fatty acids. Malealdehyde (MLA) and 4-hydroxy-2,3-trans-penten-1-al (4-HPE) inhibit rat liver glucose-6-phosphatase activity in vitro. With MLA inhibition is significant at 0.25 mM concentration. With 4-HPE inhibition takes place at 0.5 mM. 1 mM MLA inhibited by about 89%, 6 mM -HPE by about 67%. Maximal inhibition is present as early as 5 min after addition of both aldehydes. Preincubation of aldehydes with 2 mM cystein or glycine in the absence of microsomes almost completely prevents the inhibitory influence. Previous incubation of microsomes with 2 mM glutathione or 2 mM dithiothreitol or 2 mM cysteine affords a good protection towards the inhibitory action of the aldehydes; on the contrary, no protection is seen when microsomes are preincubated in the presence of either 2 mM glycine or asparagine. The total content of microsomes -SH groups is strongly decreased after incubation with 2mM malealdehyde. These results support the idea that the two aldehydes inhibit glucose-6-phosphatase mostly through interaction with protein -SH groups. The possibility that aldehydes derivated from the peroxidative decomposition of lipids may play a cooperative role in the inhibition of glucose-6-phosphatase occurring early after CCl4-poisoning is discussed.", "contents": "Inhibition by aldehydes as a possible further mechanism for glucose-6-phosphatase inactivation during CCl4-poisoning. Diffusable aldehydes are known to be produced during lipoperoxidative deterioration of unsaturated fatty acids. Malealdehyde (MLA) and 4-hydroxy-2,3-trans-penten-1-al (4-HPE) inhibit rat liver glucose-6-phosphatase activity in vitro. With MLA inhibition is significant at 0.25 mM concentration. With 4-HPE inhibition takes place at 0.5 mM. 1 mM MLA inhibited by about 89%, 6 mM -HPE by about 67%. Maximal inhibition is present as early as 5 min after addition of both aldehydes. Preincubation of aldehydes with 2 mM cystein or glycine in the absence of microsomes almost completely prevents the inhibitory influence. Previous incubation of microsomes with 2 mM glutathione or 2 mM dithiothreitol or 2 mM cysteine affords a good protection towards the inhibitory action of the aldehydes; on the contrary, no protection is seen when microsomes are preincubated in the presence of either 2 mM glycine or asparagine. The total content of microsomes -SH groups is strongly decreased after incubation with 2mM malealdehyde. These results support the idea that the two aldehydes inhibit glucose-6-phosphatase mostly through interaction with protein -SH groups. The possibility that aldehydes derivated from the peroxidative decomposition of lipids may play a cooperative role in the inhibition of glucose-6-phosphatase occurring early after CCl4-poisoning is discussed."}
{"id": "PMID:200377", "title": "[Inhibition of corticotropic function by administration of GABA in carp (Cyprinus carpio L.)].", "content": "The intracardiac injection (50 microgram/g) of GABA to Carps clearly inhibits the rise of the plasma cortisol level which occurs usually in response to the blood sampling manipulations. The inhibition starts thirty minutes after injection and lasts till the end of the experiment two hours later. The hypothesis that this neurotransmitter has a regulatory function on the corticotrop cells, especially on the excretion of ACTH has to be considered.", "contents": "[Inhibition of corticotropic function by administration of GABA in carp (Cyprinus carpio L.)]. The intracardiac injection (50 microgram/g) of GABA to Carps clearly inhibits the rise of the plasma cortisol level which occurs usually in response to the blood sampling manipulations. The inhibition starts thirty minutes after injection and lasts till the end of the experiment two hours later. The hypothesis that this neurotransmitter has a regulatory function on the corticotrop cells, especially on the excretion of ACTH has to be considered."}
{"id": "PMID:200378", "title": "Influence of salts on Michaelis-constant values for NADH.", "content": "We previously observed [Clin. Chem. 22, 1648 (1976)] that values of the Michaelis constant for NADH for the conversion of pyruvate to lactate with lactate dehydrogenase (EC 1.1.1.27) in the presence of 0.1 mol/liter buffers at 25 degrees C showed first-order dependence on enzyme concentration. This is now recognized to be the result of an inhibitory influence exerted by buffers [NH4HCO2, tris(hydroxymethyl)aminomethane, and phosphate] and salts [(NH4)2SO4 and NaCl] present in the reaction mixtures. Inhibition constants for the enzyme/inhibitor complexes formed with these substances are about 0.3 mol/liter for competition of NH4HCO3 with NaOH and 0.4 mol/liter for competition of NH4HCO3 with pyruvate; they are 0.6 mol/liter for NaCl, 1.0 mol/liter for sodium phosphate, 0.3 mol/liter for (NH4)2SO4, and 0.8 mol/liter for tris(hydroxymethyl)aminomethane when these substances compete with NADH. Because of the large molar ratio of buffer to substrate (about 10(9):1) in enzymatic assays, the buffer concentration significantly influences the Michaelis constant, despite the large value for the inhibition constant. Attention to the concentrations of these substances may be required for decreasing variability in clinical assays in which lactate dehydrogenase and possible other enzymes are used.", "contents": "Influence of salts on Michaelis-constant values for NADH. We previously observed [Clin. Chem. 22, 1648 (1976)] that values of the Michaelis constant for NADH for the conversion of pyruvate to lactate with lactate dehydrogenase (EC 1.1.1.27) in the presence of 0.1 mol/liter buffers at 25 degrees C showed first-order dependence on enzyme concentration. This is now recognized to be the result of an inhibitory influence exerted by buffers [NH4HCO2, tris(hydroxymethyl)aminomethane, and phosphate] and salts [(NH4)2SO4 and NaCl] present in the reaction mixtures. Inhibition constants for the enzyme/inhibitor complexes formed with these substances are about 0.3 mol/liter for competition of NH4HCO3 with NaOH and 0.4 mol/liter for competition of NH4HCO3 with pyruvate; they are 0.6 mol/liter for NaCl, 1.0 mol/liter for sodium phosphate, 0.3 mol/liter for (NH4)2SO4, and 0.8 mol/liter for tris(hydroxymethyl)aminomethane when these substances compete with NADH. Because of the large molar ratio of buffer to substrate (about 10(9):1) in enzymatic assays, the buffer concentration significantly influences the Michaelis constant, despite the large value for the inhibition constant. Attention to the concentrations of these substances may be required for decreasing variability in clinical assays in which lactate dehydrogenase and possible other enzymes are used."}
{"id": "PMID:200379", "title": "4-Nitrophenol in 4-nitrophenyl phosphate, a substrate for alkaline phosphatase, as measured by paired-ion high-performance liquid chromatography.", "content": "We used paired-ion high-performance liquid chromatography to determine the 4-nitrophenol content of 4-nitrophenyl phosphate, a substrate for alkaline phosphatase analysis. This was done on a reversed-phase column with a mobile phase of methanol/water, 45/55 by vol, containing 3 ml of tetrabutylammonium phosphate reagent per 200 ml of solvent. At a flow rate of 1 ml/min, 4-nitrophenol was eluted at 9 min and monitored at 404 nm; 4-nitrophenyl phosphate was eluted at 5 min and could be monitored at 311 nm. Samples of 4-nitrophenyl phosphate obtained from several sources contained 0.3 to 7.8 mole of 4-nitrophenol per mole of 4-nitrophenyl phosphate.", "contents": "4-Nitrophenol in 4-nitrophenyl phosphate, a substrate for alkaline phosphatase, as measured by paired-ion high-performance liquid chromatography. We used paired-ion high-performance liquid chromatography to determine the 4-nitrophenol content of 4-nitrophenyl phosphate, a substrate for alkaline phosphatase analysis. This was done on a reversed-phase column with a mobile phase of methanol/water, 45/55 by vol, containing 3 ml of tetrabutylammonium phosphate reagent per 200 ml of solvent. At a flow rate of 1 ml/min, 4-nitrophenol was eluted at 9 min and monitored at 404 nm; 4-nitrophenyl phosphate was eluted at 5 min and could be monitored at 311 nm. Samples of 4-nitrophenyl phosphate obtained from several sources contained 0.3 to 7.8 mole of 4-nitrophenol per mole of 4-nitrophenyl phosphate."}
{"id": "PMID:200381", "title": "A method for measurement of low levels of guanosine 3',5'-cylic monophosphate in blood plasma.", "content": "A very sensitive method is described for the assay of guanosine 3',5'-cyclic monophosphate (cGMP) based on a competitive protein-binding technique. The procedure is simple to carry out, and does not require the purchase of expensive reagents. The binding-protein used is extracted from rat lungs and the bound and unbound cGMP are separated by ammonium sulphate precipitation. Although prior extraction of the cGMP is required, the time for this extra step is easily compensated for by the shortness of the assay time. The mean cGMP found in the blood plasma of normal young males and females is 9.9 +/- 2.4 (S.D.) nmol/l (range 5.9--14.3 nmol/l) and 9.5 +/- 2.1 (S.D.) nmol/l (range 6.9--12.7 nmol/l), respectively.", "contents": "A method for measurement of low levels of guanosine 3',5'-cylic monophosphate in blood plasma. A very sensitive method is described for the assay of guanosine 3',5'-cyclic monophosphate (cGMP) based on a competitive protein-binding technique. The procedure is simple to carry out, and does not require the purchase of expensive reagents. The binding-protein used is extracted from rat lungs and the bound and unbound cGMP are separated by ammonium sulphate precipitation. Although prior extraction of the cGMP is required, the time for this extra step is easily compensated for by the shortness of the assay time. The mean cGMP found in the blood plasma of normal young males and females is 9.9 +/- 2.4 (S.D.) nmol/l (range 5.9--14.3 nmol/l) and 9.5 +/- 2.1 (S.D.) nmol/l (range 6.9--12.7 nmol/l), respectively."}
{"id": "PMID:200389", "title": "Cerebrotendinous cholestanolosis in relation to other cerebral xanthomatoses.", "content": "A synopsis is given of 37 reported patients with cerebrotendinous xanthomatosis; divided in 11 possible, but not proven cases of C.T.Ch (cerebrotendinous cholestanolosis), and 26 proven cases. An increased content of cholestanol in serum or tissue, was used as the main criterion. The ophthalmological and neurological signs are tabulated. Attention is drawn to the fact that cholestanol is not mentioned in the extensive literature on related diseases with possible cerebrospinal xanthomas, such as eosinophilic granulomatosis and hyperlipoproteinemia. The importance of a possible role of cholestanol in these diseases is stressed. A hypothetical form of cerebrotendinous cholesterolosis is discussed. A family with a sibship of parents and twelve children, three of which showed C.T.Ch is described. The development of the clinical picture confirmed the variable expression of the autosomal recessive disease. Two patients showed disturbances of steroid metabolism. A first contribution to the search for linkage with the H.L.A. system is presented. Cholestanol over cholesterol ratio, appeared to be independent of the type of lipoprotein. In search for therapy we found in patients with hyperlipoproteinemia type II A, that cholestyramine alone gave dangerously high blood levels of cholestanol; in combined treatment of cholestyramine with clofibrate cholestanol, levels were comparable to those of the controls. The possibilities of therapy are discussed.", "contents": "Cerebrotendinous cholestanolosis in relation to other cerebral xanthomatoses. A synopsis is given of 37 reported patients with cerebrotendinous xanthomatosis; divided in 11 possible, but not proven cases of C.T.Ch (cerebrotendinous cholestanolosis), and 26 proven cases. An increased content of cholestanol in serum or tissue, was used as the main criterion. The ophthalmological and neurological signs are tabulated. Attention is drawn to the fact that cholestanol is not mentioned in the extensive literature on related diseases with possible cerebrospinal xanthomas, such as eosinophilic granulomatosis and hyperlipoproteinemia. The importance of a possible role of cholestanol in these diseases is stressed. A hypothetical form of cerebrotendinous cholesterolosis is discussed. A family with a sibship of parents and twelve children, three of which showed C.T.Ch is described. The development of the clinical picture confirmed the variable expression of the autosomal recessive disease. Two patients showed disturbances of steroid metabolism. A first contribution to the search for linkage with the H.L.A. system is presented. Cholestanol over cholesterol ratio, appeared to be independent of the type of lipoprotein. In search for therapy we found in patients with hyperlipoproteinemia type II A, that cholestyramine alone gave dangerously high blood levels of cholestanol; in combined treatment of cholestyramine with clofibrate cholestanol, levels were comparable to those of the controls. The possibilities of therapy are discussed."}
{"id": "PMID:200390", "title": "Concepts in undergraduate neurological teaching.", "content": "Common neurological problems in family practice were determined to assess what knowledge of neurology is essential to the graduating medical student. The family practitioner's difficulties in managing these problems and needs for referral, were studied. Types of problems seen in a teaching hospital neurology service were also examined. Neurological problems are important if they are common, require therapy, or demand emergency management. However, dealing with these problems family practitioners report considerable difficulties. An approach to medical training is outlined in an effort to assist future physicians in handling the neurological problems of daily practice with competence and confidence.", "contents": "Concepts in undergraduate neurological teaching. Common neurological problems in family practice were determined to assess what knowledge of neurology is essential to the graduating medical student. The family practitioner's difficulties in managing these problems and needs for referral, were studied. Types of problems seen in a teaching hospital neurology service were also examined. Neurological problems are important if they are common, require therapy, or demand emergency management. However, dealing with these problems family practitioners report considerable difficulties. An approach to medical training is outlined in an effort to assist future physicians in handling the neurological problems of daily practice with competence and confidence."}
{"id": "PMID:200391", "title": "Computed tomography of intracerebral hematoma.", "content": "The C.T. findings of 33 intracerebral hematomas are described. During the first week intracerebral hematomas were visible as a sharply demarcated lesion with markedly increased density without contrast enhancement. Thereafter the density decreased gradually and after 30 days the density was always lower than that of cerebral tissue. Depending on the etiology of the hemorrhage, differences were found in the localization, shape and density of the lesion on the C.T. scan. Secondary mass effects could be evaluated precisely. On first interpretation, 94% of the hematomas were recognized as focal lesions (2 false negative) and 85% as intracerebral hematomas (2 false negative and 3 incorrect). False positives were absent. The review C.T. diagnosis was correct in 94%. In the diagnosis of intracerebral hematomas, C.T. was found to be superior to all other investigations both quantitatively and qualitatively. C.T. also has therapeutic consequences since the operability can be much better judged than before.", "contents": "Computed tomography of intracerebral hematoma. The C.T. findings of 33 intracerebral hematomas are described. During the first week intracerebral hematomas were visible as a sharply demarcated lesion with markedly increased density without contrast enhancement. Thereafter the density decreased gradually and after 30 days the density was always lower than that of cerebral tissue. Depending on the etiology of the hemorrhage, differences were found in the localization, shape and density of the lesion on the C.T. scan. Secondary mass effects could be evaluated precisely. On first interpretation, 94% of the hematomas were recognized as focal lesions (2 false negative) and 85% as intracerebral hematomas (2 false negative and 3 incorrect). False positives were absent. The review C.T. diagnosis was correct in 94%. In the diagnosis of intracerebral hematomas, C.T. was found to be superior to all other investigations both quantitatively and qualitatively. C.T. also has therapeutic consequences since the operability can be much better judged than before."}
{"id": "PMID:200392", "title": "Computed tomography of extracerebral hematoma.", "content": "The appearance on C.T. of 30 extracerebral hematomas is described. Acute subdural hematomas were seen as bandlike lesions with markedly increased, homogenous density. Epidural hematomas demonstrated a high density and a biconvex, lenticular shape. During the process of liquefaction the density decreases and three hematomas appeared as isodense lesions. The majority of chronic subdural hematomas presented a mildly to moderately decreased, nonhomogenous density, the clearly identifiable inner wall of the lesion being either convex or concave. Subdural hygromas showed a homogeneous, markedly decreased density. Almost all the hematomas caused compression of the homolateral lateral ventricle and displacement of midline structures, particularly of the septum pellucidum. In 60% of the hematomas a dilatation of the contralateral lateral ventricle, predominantly of the posterior part was seen. Acute hematomas presented oedema in varying degrees, in chronic hematomas oedema was usually absent. In the original interpretation extracerebral hematomas were recognized as a lesion on C.T. in 97% (1 false negative result), in 90%, the lesion was correctly diagnosed as an extracerebral hematoma (1 false negative and 2 incorrect). The series contained one false positive C.T. scan and 2 intracerebral hematomas were interpreted incorrectly as subdural hematomas. The review C.T. diagnosis proved to be correct in 100%. C.T. and angiography appeared to have about the same diagnostic accuracy. However, C.T. is a non invasive investigation and it provides valuable additional information with regard to all the intracranial contents. Therefore C.T. should be the method of first choice in the diagnosis of extracerebral hematomas.", "contents": "Computed tomography of extracerebral hematoma. The appearance on C.T. of 30 extracerebral hematomas is described. Acute subdural hematomas were seen as bandlike lesions with markedly increased, homogenous density. Epidural hematomas demonstrated a high density and a biconvex, lenticular shape. During the process of liquefaction the density decreases and three hematomas appeared as isodense lesions. The majority of chronic subdural hematomas presented a mildly to moderately decreased, nonhomogenous density, the clearly identifiable inner wall of the lesion being either convex or concave. Subdural hygromas showed a homogeneous, markedly decreased density. Almost all the hematomas caused compression of the homolateral lateral ventricle and displacement of midline structures, particularly of the septum pellucidum. In 60% of the hematomas a dilatation of the contralateral lateral ventricle, predominantly of the posterior part was seen. Acute hematomas presented oedema in varying degrees, in chronic hematomas oedema was usually absent. In the original interpretation extracerebral hematomas were recognized as a lesion on C.T. in 97% (1 false negative result), in 90%, the lesion was correctly diagnosed as an extracerebral hematoma (1 false negative and 2 incorrect). The series contained one false positive C.T. scan and 2 intracerebral hematomas were interpreted incorrectly as subdural hematomas. The review C.T. diagnosis proved to be correct in 100%. C.T. and angiography appeared to have about the same diagnostic accuracy. However, C.T. is a non invasive investigation and it provides valuable additional information with regard to all the intracranial contents. Therefore C.T. should be the method of first choice in the diagnosis of extracerebral hematomas."}
{"id": "PMID:200393", "title": "Neuroaxonal dystrophy, a juvenile-adult form.", "content": "This paper is an anatomoclinical study of a neuroaxonal dystrophy case, starting in childhood and evolving up to maturity, which may be considered as a juvenile-adult form of this syndrome. Several of the morphologic emphasized aspects suggest that this juvenile-adult form is a primary affection of the axon and therefore, may be considered as a separate entity, differing from the Hallervorden-Spatz disease.", "contents": "Neuroaxonal dystrophy, a juvenile-adult form. This paper is an anatomoclinical study of a neuroaxonal dystrophy case, starting in childhood and evolving up to maturity, which may be considered as a juvenile-adult form of this syndrome. Several of the morphologic emphasized aspects suggest that this juvenile-adult form is a primary affection of the axon and therefore, may be considered as a separate entity, differing from the Hallervorden-Spatz disease."}
{"id": "PMID:200394", "title": "Paraganglioma of cauda equina.", "content": "After a brief introduction to the problem of the nature and localisation of sympathetic and parasympathetic paragangliomas a new case of paraganglioma of cauda equina is reported.", "contents": "Paraganglioma of cauda equina. After a brief introduction to the problem of the nature and localisation of sympathetic and parasympathetic paragangliomas a new case of paraganglioma of cauda equina is reported."}
{"id": "PMID:200395", "title": "Noninvasive monitoring of beta-adrenergic tone during isoproterenol infusions.", "content": "Sphygmo-Recording is a simple, noninvasive technique for analysis of pulse wave contour and timing which has been used to evaluate the change in cardiac dynamics during isoproterenol infusion. The QKd interval, i.e., the time interval between the onset of the QRS complex and the onset of the Korotkoff sound at the brachial artery when the sphygomomanometer cuff is at diastolic pressure, is normally 205 +/- 15 msec. Continuous intravenous infusion of isoproterenol at 0.01, 0.02, and 0.03 microgram/kg/min into 12 euthyroid normotensive adult volunteers for 10-min intervals resulted in decreases of 55, 79, and 89 msec in QKd and increases of heart rate of 14, 27, and 43 beats/min, respectively. The corresponding changes in dP/dt, i.e., slope of the pulse wave upstroke at the brachial artery determined noninvasively from the same records, were 0.65, 1.47, and 2.26 mm Hg/msec. These results confirm previous studies which indicate that the chronotropic response of normal subjects to isoproterenol infusion is comparable to that previously reported in patients with the putative \"hyperdynamic beta-adrenergic state.\"", "contents": "Noninvasive monitoring of beta-adrenergic tone during isoproterenol infusions. Sphygmo-Recording is a simple, noninvasive technique for analysis of pulse wave contour and timing which has been used to evaluate the change in cardiac dynamics during isoproterenol infusion. The QKd interval, i.e., the time interval between the onset of the QRS complex and the onset of the Korotkoff sound at the brachial artery when the sphygomomanometer cuff is at diastolic pressure, is normally 205 +/- 15 msec. Continuous intravenous infusion of isoproterenol at 0.01, 0.02, and 0.03 microgram/kg/min into 12 euthyroid normotensive adult volunteers for 10-min intervals resulted in decreases of 55, 79, and 89 msec in QKd and increases of heart rate of 14, 27, and 43 beats/min, respectively. The corresponding changes in dP/dt, i.e., slope of the pulse wave upstroke at the brachial artery determined noninvasively from the same records, were 0.65, 1.47, and 2.26 mm Hg/msec. These results confirm previous studies which indicate that the chronotropic response of normal subjects to isoproterenol infusion is comparable to that previously reported in patients with the putative \"hyperdynamic beta-adrenergic state.\""}
{"id": "PMID:200398", "title": "Collagen and non-collagen protein synthesis in the lungs of rats exposed to a trypsin aerosol.", "content": "In rat lungs, 24 h after a 10 min inhalation of a nebulized 1% (w/v) trypsin solution, there was a 25% increase in lung weight. The incorporation of 3H-tryptophane and 2,3-[3H]-proline into trichloroacetic acid insoluble material was decreased although there was no alteration in prolyl hydroxylase activity. Although hydroxyproline formation was decreased, this decrease was probably due to the general decrease in protein synthesis. Ninety-six hours after inhalation of the trypsin solution there was an increase in non-collagen protein biosynthesis. Proline incorporation and hydroxyproline formation were both increased more than the tryptophane incorporation increase at this same time point. These increases were accompanied by an increase in prolyl hydroxylase activity. These experiments indicate that major changes in protein biosynthesis occur in lung tissues after inhalation of proteolytic enzymes and demonstrate the temporal biochemical changes which occur in lung injury.", "contents": "Collagen and non-collagen protein synthesis in the lungs of rats exposed to a trypsin aerosol. In rat lungs, 24 h after a 10 min inhalation of a nebulized 1% (w/v) trypsin solution, there was a 25% increase in lung weight. The incorporation of 3H-tryptophane and 2,3-[3H]-proline into trichloroacetic acid insoluble material was decreased although there was no alteration in prolyl hydroxylase activity. Although hydroxyproline formation was decreased, this decrease was probably due to the general decrease in protein synthesis. Ninety-six hours after inhalation of the trypsin solution there was an increase in non-collagen protein biosynthesis. Proline incorporation and hydroxyproline formation were both increased more than the tryptophane incorporation increase at this same time point. These increases were accompanied by an increase in prolyl hydroxylase activity. These experiments indicate that major changes in protein biosynthesis occur in lung tissues after inhalation of proteolytic enzymes and demonstrate the temporal biochemical changes which occur in lung injury."}
{"id": "PMID:200399", "title": "Extractable collagenase and carcinogenesis of the mouse skin.", "content": "Collagenolytic activity has been demonstrated in the early phase of chemical carcinogenesis of mouse skin following 3-methylcholanthrene application dropwise in acetone or painted on the skin in benzene. In addition very high levels of collagenase could be detected in mouse skin papillomas and carcinomas. In all the tissues investigated, collagenase activity was extracted from the 6000 X g sediment of tissue homogenates with 5 M urea in 50 mM Tris-HCl buffer, pH 7.5. After dialyzing the extract, the enzyme was precipitated with ammonium sulfate and the activity determined against 14C-collagen substrate in solution. This procedure was found suitable for the detection and estimation of collagenase activity in skin tissues with high turnover of collagen and thus offers an attractive alternative to tissue culture methods.", "contents": "Extractable collagenase and carcinogenesis of the mouse skin. Collagenolytic activity has been demonstrated in the early phase of chemical carcinogenesis of mouse skin following 3-methylcholanthrene application dropwise in acetone or painted on the skin in benzene. In addition very high levels of collagenase could be detected in mouse skin papillomas and carcinomas. In all the tissues investigated, collagenase activity was extracted from the 6000 X g sediment of tissue homogenates with 5 M urea in 50 mM Tris-HCl buffer, pH 7.5. After dialyzing the extract, the enzyme was precipitated with ammonium sulfate and the activity determined against 14C-collagen substrate in solution. This procedure was found suitable for the detection and estimation of collagenase activity in skin tissues with high turnover of collagen and thus offers an attractive alternative to tissue culture methods."}
{"id": "PMID:200401", "title": "Dream report following commissurotomy.", "content": "This paper addresses the question of right hemisphere involvement in the visual components of dreaming. The rationale derives from an observed relation between reports of visual agnosia accompanied by dream cessation and the literature on right hemisphere specialization for visuo-spatial processes. All night sleep EEGs were recorded from subjects with partial or complete section of the corpus callosum and anterior commissure. Upon entering a EEG-, EOG- and EMG-defined REM episode, the subjects were awakened and questioned about dream content. All subjects examined in this fashion were able to recount some visual dream content. This result fails to support any notion of selective right hemisphere visual dream mediation.", "contents": "Dream report following commissurotomy. This paper addresses the question of right hemisphere involvement in the visual components of dreaming. The rationale derives from an observed relation between reports of visual agnosia accompanied by dream cessation and the literature on right hemisphere specialization for visuo-spatial processes. All night sleep EEGs were recorded from subjects with partial or complete section of the corpus callosum and anterior commissure. Upon entering a EEG-, EOG- and EMG-defined REM episode, the subjects were awakened and questioned about dream content. All subjects examined in this fashion were able to recount some visual dream content. This result fails to support any notion of selective right hemisphere visual dream mediation."}
{"id": "PMID:200402", "title": "Practical problems in clinical enzymology.", "content": "It is possible to carry out precise determinations of the activity of the clinically important serum enzymes with continuous monitoring (kinetic) methods. Care must be taken that the induction period has passed before the first measurement is taken and that the reading is taken from the zero-order, linear part of the curve. Special precautions must be taken with highly active sera that are also turbid. There are no suitable enzyme standards available at present; therefore, standardization of the instrument is of utmost importance. The instrument must be able to produce the theoretical molar absorptivity of the substrate or cofactor. The instrument must be calibrated for wavelength and absorbance accuracy with nationally accepted standards. Some reference methods are beginning to appear; if widely adopted, they should improve the interlaboratory comparability of enzyme assays. Instrument and method standardization plus well-characterized enzyme standards, when available, will reduce the variability of intra- and interlaboratory enzyme assays.", "contents": "Practical problems in clinical enzymology. It is possible to carry out precise determinations of the activity of the clinically important serum enzymes with continuous monitoring (kinetic) methods. Care must be taken that the induction period has passed before the first measurement is taken and that the reading is taken from the zero-order, linear part of the curve. Special precautions must be taken with highly active sera that are also turbid. There are no suitable enzyme standards available at present; therefore, standardization of the instrument is of utmost importance. The instrument must be able to produce the theoretical molar absorptivity of the substrate or cofactor. The instrument must be calibrated for wavelength and absorbance accuracy with nationally accepted standards. Some reference methods are beginning to appear; if widely adopted, they should improve the interlaboratory comparability of enzyme assays. Instrument and method standardization plus well-characterized enzyme standards, when available, will reduce the variability of intra- and interlaboratory enzyme assays."}
{"id": "PMID:200404", "title": "Cytochrome C as antidote in mice poisoned with the mushroom toxin alpha-amanitin.", "content": "The curative potencies of cytochrome c applied 8 hours after lethal doses of alpha-amanitin in mice are confirmed. In a comprehensive series of experiments, various dosage schedules were explored. Optimal effects with cure rates approaching 100% were obtained either with repeated doses of cytochrome c or by combining it with penicillin. Male mice are more sensitive to alpha-amanitin than female mice but it was established that the antidote is effective in both sexes. Substantial cure rates are seen even when the treatment after supralethal doses of alpha-amanitin is withheld for 12 hours after the poisoning.", "contents": "Cytochrome C as antidote in mice poisoned with the mushroom toxin alpha-amanitin. The curative potencies of cytochrome c applied 8 hours after lethal doses of alpha-amanitin in mice are confirmed. In a comprehensive series of experiments, various dosage schedules were explored. Optimal effects with cure rates approaching 100% were obtained either with repeated doses of cytochrome c or by combining it with penicillin. Male mice are more sensitive to alpha-amanitin than female mice but it was established that the antidote is effective in both sexes. Substantial cure rates are seen even when the treatment after supralethal doses of alpha-amanitin is withheld for 12 hours after the poisoning."}
{"id": "PMID:200407", "title": "[The diuresis of cyclic adenosine-3'5'-monophosphate (cAMP) in primary and secondary disorders of the parathyroid glands].", "content": "The diuresis of cAMP in primary hyperparathyroidism was significantly higher at 7.3 +/- 2.5 mumol/g creatinine X 24 h (P less than 0.005) than that in healthy subjects (3.5 +/- 0.7 mumol/g creatinine X 24 h). After successful operation on the parathyroid gland, cAMP diuresis usually decreased within 24 hours to normal or subnormal values. In primary or secondary hypoparathyroidism subnormal amounts of cAMP (P less than 0.005) were excreted. The method gives false-negative results in functional disorders of the parathyroid glands accompanied or caused by renal failure.", "contents": "[The diuresis of cyclic adenosine-3'5'-monophosphate (cAMP) in primary and secondary disorders of the parathyroid glands]. The diuresis of cAMP in primary hyperparathyroidism was significantly higher at 7.3 +/- 2.5 mumol/g creatinine X 24 h (P less than 0.005) than that in healthy subjects (3.5 +/- 0.7 mumol/g creatinine X 24 h). After successful operation on the parathyroid gland, cAMP diuresis usually decreased within 24 hours to normal or subnormal values. In primary or secondary hypoparathyroidism subnormal amounts of cAMP (P less than 0.005) were excreted. The method gives false-negative results in functional disorders of the parathyroid glands accompanied or caused by renal failure."}
{"id": "PMID:200412", "title": "Biochemical pathogenesis and therapeutical prospectives in degenerative chorea.", "content": "In the last few years both neuropathological and neurochemical data have contributed towards a classification of the pathogenesis of degenerative chorea of which Huntington's chorea shows clear evidence of heredity. The role of GABA, DA and Ach in determining chorea seems clear. In 7 patients with degenerative hypotonic-hyperkinetic chorea (the acid metabolites into the cerebrospinal fluid are not available) a neuropharmacological study was conducted. The symptomatology was evaluated both through clinical rating and through phasic and tonic performance tests. The neuropharmacological tests were both acute and chronic. In the acute tests the effect of modification of various neurotransmitters (Ach, DA, NA, GABA) was evaluated. In chronic treatment the effectiveness of haloperidol, PCPA and bromocryptine was evaluated. The results of the acute study were positive both as regards increment of DA (receptors stimulation) and GABA. The chronic study shows any effect of PCPA, positive results both with bromocryptine and with haloperidol. Our results confirm a DA/GABA interaction in the pathogenesis of degenerative chorea.", "contents": "Biochemical pathogenesis and therapeutical prospectives in degenerative chorea. In the last few years both neuropathological and neurochemical data have contributed towards a classification of the pathogenesis of degenerative chorea of which Huntington's chorea shows clear evidence of heredity. The role of GABA, DA and Ach in determining chorea seems clear. In 7 patients with degenerative hypotonic-hyperkinetic chorea (the acid metabolites into the cerebrospinal fluid are not available) a neuropharmacological study was conducted. The symptomatology was evaluated both through clinical rating and through phasic and tonic performance tests. The neuropharmacological tests were both acute and chronic. In the acute tests the effect of modification of various neurotransmitters (Ach, DA, NA, GABA) was evaluated. In chronic treatment the effectiveness of haloperidol, PCPA and bromocryptine was evaluated. The results of the acute study were positive both as regards increment of DA (receptors stimulation) and GABA. The chronic study shows any effect of PCPA, positive results both with bromocryptine and with haloperidol. Our results confirm a DA/GABA interaction in the pathogenesis of degenerative chorea."}
{"id": "PMID:200413", "title": "Failure of neurotransmitter blockers to alter PGE2-induced LH release.", "content": "The purpose of this study is to ascertain whether or not prostaglandin (PG) E2 induces LH release by modifying or modulating the release or action of neural transmitters. PGE2 injected iv into spayed rats primed two days earlier with 10 microgram estradiol benzoate increased the plasma levels of LH 10 min later as measured by radioimmunoassay. The peak of plasma LH was not changed by prior treatment with beta- or alpha-adrenergic receptor blockers, propranolol or phenoxybenzamine. The peak level of plasma LH did not alter in rats treated with DL-alpha-methyl-p-tyrosine methyl ester HCl (alpha-MPT) or sodium diethyldithiocarbamate (DDC). Similarly, the peak of plasma LH was not changed by prior treatment with imipramine. Administration of PGE2 produced an increase in anterior pituitary and plasma, but not hypothalamic cyclic AMP concomitantly with the elevation in plasma LH. Although it is possible that the effect of PGE2 could be mediated by another transmitter system, as yet unknown, or that the effect of PGE2 on LH release could be mediated via the adenylate cyclase-cyclic AMP system, the results indicate that PGE2 does not act trans-synaptically, but probably acts directly on LH-RH neurons.", "contents": "Failure of neurotransmitter blockers to alter PGE2-induced LH release. The purpose of this study is to ascertain whether or not prostaglandin (PG) E2 induces LH release by modifying or modulating the release or action of neural transmitters. PGE2 injected iv into spayed rats primed two days earlier with 10 microgram estradiol benzoate increased the plasma levels of LH 10 min later as measured by radioimmunoassay. The peak of plasma LH was not changed by prior treatment with beta- or alpha-adrenergic receptor blockers, propranolol or phenoxybenzamine. The peak level of plasma LH did not alter in rats treated with DL-alpha-methyl-p-tyrosine methyl ester HCl (alpha-MPT) or sodium diethyldithiocarbamate (DDC). Similarly, the peak of plasma LH was not changed by prior treatment with imipramine. Administration of PGE2 produced an increase in anterior pituitary and plasma, but not hypothalamic cyclic AMP concomitantly with the elevation in plasma LH. Although it is possible that the effect of PGE2 could be mediated by another transmitter system, as yet unknown, or that the effect of PGE2 on LH release could be mediated via the adenylate cyclase-cyclic AMP system, the results indicate that PGE2 does not act trans-synaptically, but probably acts directly on LH-RH neurons."}
{"id": "PMID:200414", "title": "Effects of biogenic amines on the formation of adenosine 3',5'-monophosphate in human thyroid slices.", "content": "The effects of various concentrations of biogenic amines on the formation of adenosine-3', 5'-monophosphate (cyclic AMP) and their interactions with other thyroid stimulators were investigated in human thyroid slices from normal and Graves' disease. Most of biogenic amines were found to have the stimulatory effects to some extent. Among the biogenic amines tested, histamine was the most potent thyroid stimulator, norepinephrine and serotonin, the intermediate in terms of cyclic AMP formation. The effect of histamine was almost as potent as TSH in thyroid slices from Graves' disease. This stimulatory effect of histamine was blocked by metiamide, a histamine H2-receptor antagonist, but not by chlorpheniramine, a histamine H1-receptor antagonist. The effect of norepinephrine was completely inhibited by propranolol, but not by phentolamine. Polyphloretin phosphate did not inhibit norepinephrine- or histamine-induced cyclic AMP formation, while it significantly depressed cyclic AMP formation induced by prostaglandin E2. The maximal effect of histamine was additive to that of TSH. It is suggested that biogenic amines, histamine and norepinephrine, in particular, have the thyroid receptors different from that of TSH or prostaglandin E2 and could play an important role in thyroid physiology.", "contents": "Effects of biogenic amines on the formation of adenosine 3',5'-monophosphate in human thyroid slices. The effects of various concentrations of biogenic amines on the formation of adenosine-3', 5'-monophosphate (cyclic AMP) and their interactions with other thyroid stimulators were investigated in human thyroid slices from normal and Graves' disease. Most of biogenic amines were found to have the stimulatory effects to some extent. Among the biogenic amines tested, histamine was the most potent thyroid stimulator, norepinephrine and serotonin, the intermediate in terms of cyclic AMP formation. The effect of histamine was almost as potent as TSH in thyroid slices from Graves' disease. This stimulatory effect of histamine was blocked by metiamide, a histamine H2-receptor antagonist, but not by chlorpheniramine, a histamine H1-receptor antagonist. The effect of norepinephrine was completely inhibited by propranolol, but not by phentolamine. Polyphloretin phosphate did not inhibit norepinephrine- or histamine-induced cyclic AMP formation, while it significantly depressed cyclic AMP formation induced by prostaglandin E2. The maximal effect of histamine was additive to that of TSH. It is suggested that biogenic amines, histamine and norepinephrine, in particular, have the thyroid receptors different from that of TSH or prostaglandin E2 and could play an important role in thyroid physiology."}
{"id": "PMID:200416", "title": "Correlation of ovarian binding of 125I-HCG with formation of cAMP, estradiol and progesterone during pregnancy.", "content": "The content of ovarian gonadotropin receptors in rat was found to change during pregnancy. The specific binding of 125I-HCG to ovarian homogenates rose to its maximal values on days 13 and 16. Thereafter, the binding declined as parturition approached. No consistent changes in responsiveness of rat ovary to LH in synthesis of cAMP and estradiol were observed during pregnancy. Plasma estradiol concentration increased on day 16 and remained high throught days 21 and 22. Progesterone levels increase steadily during the first half of pregnancy and then fall, especially sharply on day 21 and 22. The results demonstrate that the secretion of progesterone correlates with gonadotropin receptors during pregnancy.", "contents": "Correlation of ovarian binding of 125I-HCG with formation of cAMP, estradiol and progesterone during pregnancy. The content of ovarian gonadotropin receptors in rat was found to change during pregnancy. The specific binding of 125I-HCG to ovarian homogenates rose to its maximal values on days 13 and 16. Thereafter, the binding declined as parturition approached. No consistent changes in responsiveness of rat ovary to LH in synthesis of cAMP and estradiol were observed during pregnancy. Plasma estradiol concentration increased on day 16 and remained high throught days 21 and 22. Progesterone levels increase steadily during the first half of pregnancy and then fall, especially sharply on day 21 and 22. The results demonstrate that the secretion of progesterone correlates with gonadotropin receptors during pregnancy."}
{"id": "PMID:200418", "title": "Fructose transport in Bacillus subtilis.", "content": "The transport of fructose in Bacillus subtilis was studied in various mutant strains lacking the following activities: ATP-dependent fructokinase (fruC), the fructose 1-phosphate kinase (fruB) the phosphofructokinase (pfk), the enzyme I of the phosphoenolpyruvate phosphotransferase system (the thermosensitive mutation ptsI1), and a transport activity (fruA). Combinations of these mutations indicated that the transport of fructose in Bacillus subtilis is tightly coupled to its phosphorylation either in fructose 1-phosphate, identified in vivo and in vitro or in fructose 6-phosphate identified by indirect lines of evidence. These steps of fructose metabolism were shown to depend on the activity of the enzyme I of the phosphoenolpyruvate phosphotransferase systems. The fruA mutations affect the transport of fructose when the bacteria are submitted to catabolite repression. The mutations were localized on the chromosome of Bacillus subtilis in a cluster including the fruB gene. When grown in a medium supplemented by a mixture of potassium glutamate and succinate the fruA mutants are able to carry on the two vectorial metabolisms generating fructose 6-phosphate as well as fructose 1-phosphate. A negative search of strictly negative transport mutants in fruA strains indicated that more than two structural genes are involved in the transport of fructose.", "contents": "Fructose transport in Bacillus subtilis. The transport of fructose in Bacillus subtilis was studied in various mutant strains lacking the following activities: ATP-dependent fructokinase (fruC), the fructose 1-phosphate kinase (fruB) the phosphofructokinase (pfk), the enzyme I of the phosphoenolpyruvate phosphotransferase system (the thermosensitive mutation ptsI1), and a transport activity (fruA). Combinations of these mutations indicated that the transport of fructose in Bacillus subtilis is tightly coupled to its phosphorylation either in fructose 1-phosphate, identified in vivo and in vitro or in fructose 6-phosphate identified by indirect lines of evidence. These steps of fructose metabolism were shown to depend on the activity of the enzyme I of the phosphoenolpyruvate phosphotransferase systems. The fruA mutations affect the transport of fructose when the bacteria are submitted to catabolite repression. The mutations were localized on the chromosome of Bacillus subtilis in a cluster including the fruB gene. When grown in a medium supplemented by a mixture of potassium glutamate and succinate the fruA mutants are able to carry on the two vectorial metabolisms generating fructose 6-phosphate as well as fructose 1-phosphate. A negative search of strictly negative transport mutants in fruA strains indicated that more than two structural genes are involved in the transport of fructose."}
{"id": "PMID:200420", "title": "The modification of nuclear proteins by ADP-ribosylation.", "content": "When incubated in vitro purified mouse nuclei incorporate NAD into poly(ADP-Rib). Analysis of the product on CsDl/urea gradients showed that a large proportion of the poly(ADP-Rib) was not attached to protein. The free poly(ADP-Rib) did not appear to arise through degradation and its chain length was significantly longer than the poly(ADP-Rib) attached to proteins. Fractionation of the proteins on hydroxyapatite revealed that tissue-specific modification of both the histones and non-histone proteins, had occurred. In the case of one protein species there was evidence for the existence of several forms with different numbers of ADP-Rib residues.", "contents": "The modification of nuclear proteins by ADP-ribosylation. When incubated in vitro purified mouse nuclei incorporate NAD into poly(ADP-Rib). Analysis of the product on CsDl/urea gradients showed that a large proportion of the poly(ADP-Rib) was not attached to protein. The free poly(ADP-Rib) did not appear to arise through degradation and its chain length was significantly longer than the poly(ADP-Rib) attached to proteins. Fractionation of the proteins on hydroxyapatite revealed that tissue-specific modification of both the histones and non-histone proteins, had occurred. In the case of one protein species there was evidence for the existence of several forms with different numbers of ADP-Rib residues."}
{"id": "PMID:200422", "title": "The regulation of glutamate metabolism in Candida utilis. Evidence for two interconvertible forms of NAD-dependent glutamate dehydrogenase.", "content": "An earlier observation from this laboratory (J. Gen. Microbiol. 64, 423--427) that NAD-dependent glutamate dehydrogenase activity is modulated by rapid inactivation has been extended to show that this mechanism is completely reversible. Changes in properties of the enzyme accompany inactivation and two different forms active (a) and inactive (b) of the enzyme with distinctive properties have been isolated. Incubation of the inactive enzyme with magnesium in vitro produced a rapid increase of activity; this was accompanied by a change in the properties of the enzyme to those of the a form. This control mechanism of enzyme interconversion appears widespread among yeasts. Its probable role in modulating glutamate synthesis and degration is discussed.", "contents": "The regulation of glutamate metabolism in Candida utilis. Evidence for two interconvertible forms of NAD-dependent glutamate dehydrogenase. An earlier observation from this laboratory (J. Gen. Microbiol. 64, 423--427) that NAD-dependent glutamate dehydrogenase activity is modulated by rapid inactivation has been extended to show that this mechanism is completely reversible. Changes in properties of the enzyme accompany inactivation and two different forms active (a) and inactive (b) of the enzyme with distinctive properties have been isolated. Incubation of the inactive enzyme with magnesium in vitro produced a rapid increase of activity; this was accompanied by a change in the properties of the enzyme to those of the a form. This control mechanism of enzyme interconversion appears widespread among yeasts. Its probable role in modulating glutamate synthesis and degration is discussed."}
{"id": "PMID:200423", "title": "Development of Escherichia coli virus T1: repression of host gene expression.", "content": "Host protein synthesis, measured either as amino acid incorporation into proteins or as enzyme synthesis, is inhibited rapidly after infection Escherichia coli with T1. Analysis of this inhibition, using a technique which distinguishes between translation and transcription, revealed that translation of host mRNA is specifically blocked. Comparison of the time course of T1-induced host repression with inhibition by the drugs rifampicin, nitrofurantoin and chloramphenicol showed that T1 affects the initiation step of host translation. Intact membranes are apparently essential for host repression, suggesting a membrane-mediated process. Concomitant viral protein synthesis is not required. The membrane-altering principle is a constituent of the viral particle.", "contents": "Development of Escherichia coli virus T1: repression of host gene expression. Host protein synthesis, measured either as amino acid incorporation into proteins or as enzyme synthesis, is inhibited rapidly after infection Escherichia coli with T1. Analysis of this inhibition, using a technique which distinguishes between translation and transcription, revealed that translation of host mRNA is specifically blocked. Comparison of the time course of T1-induced host repression with inhibition by the drugs rifampicin, nitrofurantoin and chloramphenicol showed that T1 affects the initiation step of host translation. Intact membranes are apparently essential for host repression, suggesting a membrane-mediated process. Concomitant viral protein synthesis is not required. The membrane-altering principle is a constituent of the viral particle."}
{"id": "PMID:200426", "title": "Mechanism of activation of the protein kinase I from rabbit skeletal muscle. The high-affinity ATP site of the holoenzyme.", "content": "The high-affinity binding site for ATP of the holoenzyme of cAMP-dependent protein kinase (type I) from rabbit skeletal muscle has been investigated. Binding affinity of a series of ATP derivatives substituted at different sites in the molecule was determined by competition with tritiated ATP. The results were compared with data available from cAMP derivatives with the same substituents, in order to analyse the electronic and steric features of these two sites on the protein kinase. The comparison revealed significant differences of the effect of substituents towards the two sites. In particular the N6-derivatives of ATP and substituents affecting the gamma-phosphate indicate that the high-affinity ATP site of the protein kinase has similar properties as those found for phosphotransferase sites. The present results are consistent with the supposition that the high-affinity site for ATP on the holoenzyme is congruent with the phosphotransferase site of the catalytic subunit. Upon combination of catalytic and regulatory subunits this site would be transformed into a high-affinity site for ATP with simultaneous blocking of the phosphotransferase activity.", "contents": "Mechanism of activation of the protein kinase I from rabbit skeletal muscle. The high-affinity ATP site of the holoenzyme. The high-affinity binding site for ATP of the holoenzyme of cAMP-dependent protein kinase (type I) from rabbit skeletal muscle has been investigated. Binding affinity of a series of ATP derivatives substituted at different sites in the molecule was determined by competition with tritiated ATP. The results were compared with data available from cAMP derivatives with the same substituents, in order to analyse the electronic and steric features of these two sites on the protein kinase. The comparison revealed significant differences of the effect of substituents towards the two sites. In particular the N6-derivatives of ATP and substituents affecting the gamma-phosphate indicate that the high-affinity ATP site of the protein kinase has similar properties as those found for phosphotransferase sites. The present results are consistent with the supposition that the high-affinity site for ATP on the holoenzyme is congruent with the phosphotransferase site of the catalytic subunit. Upon combination of catalytic and regulatory subunits this site would be transformed into a high-affinity site for ATP with simultaneous blocking of the phosphotransferase activity."}
{"id": "PMID:200428", "title": "Effect of borate on the catalytic activities of muscle glyceraldehyde-3-phosphate dehydrogenase.", "content": "The effect of borate on glyceraldehyde-3-phosphate dehydrogenase from human, pig and rabbit muscle was studied. At lower concentration of borate only the dehydrogenase activity is inhibited, reversibly and competitively against NAD. At concentration of borate above 6 mM the plots of 1/v versus borate concentration become nonlinear and the inhibition is extended to the esterase and acetylphosphatase activities. In certain conditions a time-dependent inactivation and reactivation was observed. The direct interaction between borate (if present at concentration of at least 6 mM) and glyceraldehyde-3-phosphate dehydrogenase is postulated, the possible site of the reaction being the histidine residue(s). The esterase activity of the human muscle enzyme and the effect of borate on it are different from the other mammalian enzymes.", "contents": "Effect of borate on the catalytic activities of muscle glyceraldehyde-3-phosphate dehydrogenase. The effect of borate on glyceraldehyde-3-phosphate dehydrogenase from human, pig and rabbit muscle was studied. At lower concentration of borate only the dehydrogenase activity is inhibited, reversibly and competitively against NAD. At concentration of borate above 6 mM the plots of 1/v versus borate concentration become nonlinear and the inhibition is extended to the esterase and acetylphosphatase activities. In certain conditions a time-dependent inactivation and reactivation was observed. The direct interaction between borate (if present at concentration of at least 6 mM) and glyceraldehyde-3-phosphate dehydrogenase is postulated, the possible site of the reaction being the histidine residue(s). The esterase activity of the human muscle enzyme and the effect of borate on it are different from the other mammalian enzymes."}
{"id": "PMID:200429", "title": "Case report: Liver scintigraphy in the follow-up of a patient on cytotoxic therapy.", "content": "A 63-year-old male patient with a small cell bronchial carcinoma on cytotoxic therapy was followed up with the use of liver scintigraphy. In the various scintigrams the remission as well as the late reappearance of the liver metastasis was demonstrated. The abnormalities in the liver scintigrams correlated with the biochemical changes throughout the course.", "contents": "Case report: Liver scintigraphy in the follow-up of a patient on cytotoxic therapy. A 63-year-old male patient with a small cell bronchial carcinoma on cytotoxic therapy was followed up with the use of liver scintigraphy. In the various scintigrams the remission as well as the late reappearance of the liver metastasis was demonstrated. The abnormalities in the liver scintigrams correlated with the biochemical changes throughout the course."}
{"id": "PMID:200433", "title": "Effect of exercise and of prolonged oral administration of propranolol on haemodynamic variables, plasma renin concentration, plasma aldosterone and c-AMP.", "content": "The effect of submaximal exercise upon haemodynamic and biochemical variables was investigated in healthy male subjects, aged 17-27 years, before and at the end of 2 weeks treatment with propranolol (40 mg p.o., q.i.d.). Propranolol reduced the resting blood pressure in normal subjects significantly. This effect was due to reduction of cardiac output and of systemic vascular resistance. No effect of propranolol on BP was seen during maximal exercise, since a reduced cardiac output was accompanied by an increased peripheral resistance. The reduction of cardiac output during exercise can be compensated in part by an increase in stroke volume. The sympathetic activity induced by physical exercise in normotensives increased plasma renin concentration (PRC) and plasma aldosterone (PA), and suppressed urinary excretion of c-AMP. PRC returned to basal levels after 45 min. No increase of PRC was observed after exercise in subjects treated with propranolol. Yet the increase of PA was not completely suppressed. No direct relation was demonstrated between PRC and the haemodynamic variables before or during the administration of propranolol.", "contents": "Effect of exercise and of prolonged oral administration of propranolol on haemodynamic variables, plasma renin concentration, plasma aldosterone and c-AMP. The effect of submaximal exercise upon haemodynamic and biochemical variables was investigated in healthy male subjects, aged 17-27 years, before and at the end of 2 weeks treatment with propranolol (40 mg p.o., q.i.d.). Propranolol reduced the resting blood pressure in normal subjects significantly. This effect was due to reduction of cardiac output and of systemic vascular resistance. No effect of propranolol on BP was seen during maximal exercise, since a reduced cardiac output was accompanied by an increased peripheral resistance. The reduction of cardiac output during exercise can be compensated in part by an increase in stroke volume. The sympathetic activity induced by physical exercise in normotensives increased plasma renin concentration (PRC) and plasma aldosterone (PA), and suppressed urinary excretion of c-AMP. PRC returned to basal levels after 45 min. No increase of PRC was observed after exercise in subjects treated with propranolol. Yet the increase of PA was not completely suppressed. No direct relation was demonstrated between PRC and the haemodynamic variables before or during the administration of propranolol."}
{"id": "PMID:200435", "title": "Evaulation of the effect of fosazepam (a new benzodiazepine), nitrazepam and placebo on sleep patterns in normal subjects.", "content": "The nocturnal sleep of eight healthy young volunteers was studied after placebo, Fosazepam 100 mg and Nitrazepam 10 mg. Overall results were very similar after the two drugs. During drug periods there was less of sleep Stages I, III + IV and REM, compensated by an increase in Stage II. The decrease in SWS (III + IV) persisted during the withdrawal periods. There was also an increase in Stage I during Fosazepam withdrawal, whereas the percentage of other sleep stages returned to normal. Sleep quality was reported to be slightly better and morning drowsiness, as well as hangover effects, were said to be less pronounced after Fosazepam than after Nitrazepam.", "contents": "Evaulation of the effect of fosazepam (a new benzodiazepine), nitrazepam and placebo on sleep patterns in normal subjects. The nocturnal sleep of eight healthy young volunteers was studied after placebo, Fosazepam 100 mg and Nitrazepam 10 mg. Overall results were very similar after the two drugs. During drug periods there was less of sleep Stages I, III + IV and REM, compensated by an increase in Stage II. The decrease in SWS (III + IV) persisted during the withdrawal periods. There was also an increase in Stage I during Fosazepam withdrawal, whereas the percentage of other sleep stages returned to normal. Sleep quality was reported to be slightly better and morning drowsiness, as well as hangover effects, were said to be less pronounced after Fosazepam than after Nitrazepam."}
{"id": "PMID:200436", "title": "Smoking and catecholamine and c-AMP concentrations in the coronary circulation of man and the effect of oxprenolol.", "content": "Changes in catecholamine, c-AMP and lactate concentrations in the coronary circulation of man, during smoking, were studied in 12 patients. The heart rate increase from 63 +/- 2 beats/min (control) to 74 +/- 3 (smoking)(P less than 0.01), falling to 70 +/- 2 (10 min after smoking) (0.05 greater than P greater than 0.01), whilst coronary sinus c-AMP concentrations rose from 11 +/- 0.7 nmol/l (smoking) to 11.9 +/- 0.8 nmol/l (after smoking) (0.05 greater than P greater than 0.01; one tailed 't' test). There was no significant change in blood pressure, catecholamine or lactate concentrations. The study was repeated in eight of the patients following intravenous oxprenolol. Coronary sinus catecholamine concentrations increased from 4.1 +/- 0.7 nmol/l (control) to 5.5 +/- 1.1 nmol/l (after smoking) (0.05 greater than P greater than 0.01; one tailed 't' test), but heart rate and c-AMP concentrations remained unchanged, confirming that smoking-induced tachycardia is a result of a beta-adrenergic mechanism, at least part of which is due to a release of cardiac catecholamines. Arterial lactate concentrations increased only following oxprenolol from 0.74 +/- 0.07 mmol/l (control) to 0.83 +/- 0.09 mmol/l (smoking).", "contents": "Smoking and catecholamine and c-AMP concentrations in the coronary circulation of man and the effect of oxprenolol. Changes in catecholamine, c-AMP and lactate concentrations in the coronary circulation of man, during smoking, were studied in 12 patients. The heart rate increase from 63 +/- 2 beats/min (control) to 74 +/- 3 (smoking)(P less than 0.01), falling to 70 +/- 2 (10 min after smoking) (0.05 greater than P greater than 0.01), whilst coronary sinus c-AMP concentrations rose from 11 +/- 0.7 nmol/l (smoking) to 11.9 +/- 0.8 nmol/l (after smoking) (0.05 greater than P greater than 0.01; one tailed 't' test). There was no significant change in blood pressure, catecholamine or lactate concentrations. The study was repeated in eight of the patients following intravenous oxprenolol. Coronary sinus catecholamine concentrations increased from 4.1 +/- 0.7 nmol/l (control) to 5.5 +/- 1.1 nmol/l (after smoking) (0.05 greater than P greater than 0.01; one tailed 't' test), but heart rate and c-AMP concentrations remained unchanged, confirming that smoking-induced tachycardia is a result of a beta-adrenergic mechanism, at least part of which is due to a release of cardiac catecholamines. Arterial lactate concentrations increased only following oxprenolol from 0.74 +/- 0.07 mmol/l (control) to 0.83 +/- 0.09 mmol/l (smoking)."}
{"id": "PMID:200437", "title": "Central and peripheral alpha-adrenergic effects of some imidazolidines.", "content": "The central hypotensive activity of clonidine and of 12 structurally related analogues was determined following intravenous administration to pentobarbital-anaesthetized, normotensive rats. This sympathoinhibitory action was characterized by means of a pC30, calculated from dose-response curves. The centrally mediated depressor activity (pC30) was correlated with the peripherally induced pressor activity of the compounds (pC100) reported on previously and which had been established after intravenous application to pithed rats. In these correlations, the quantitative ability of the substances to penetrate into the central nervous system had been taken into account. The octanol/buffer (pH = 7.4) partition coefficients were used as a measure of lipophilic behaviour. A positive correlation was found between the central hypotensive activity and the linear combination of peripheral alpha-sympathomimetic activity and lipophilicity.", "contents": "Central and peripheral alpha-adrenergic effects of some imidazolidines. The central hypotensive activity of clonidine and of 12 structurally related analogues was determined following intravenous administration to pentobarbital-anaesthetized, normotensive rats. This sympathoinhibitory action was characterized by means of a pC30, calculated from dose-response curves. The centrally mediated depressor activity (pC30) was correlated with the peripherally induced pressor activity of the compounds (pC100) reported on previously and which had been established after intravenous application to pithed rats. In these correlations, the quantitative ability of the substances to penetrate into the central nervous system had been taken into account. The octanol/buffer (pH = 7.4) partition coefficients were used as a measure of lipophilic behaviour. A positive correlation was found between the central hypotensive activity and the linear combination of peripheral alpha-sympathomimetic activity and lipophilicity."}
{"id": "PMID:200439", "title": "Properties of the peripheral opiate receptors in the cat nictitating membrane.", "content": "The noradrenaline overflow and the contractile response elicited by nerve stimulation of the muscle were inhibited by 1 micron morphine in the cat nictitating membrane. This concentration of morphine did not modify the response of the muscle to exogenous noradrenaline. The inhibitory effect of morphine was increased by low Na+ (50 mM), whereas the capacity of naloxone as antagonist to morphine was higher with 150 mM than with 50 mM Na+. These results suggest that the peripheral opiate receptors which interact with noradrenergic neurotransmission could show a sodium allosteric transformation similar to that described for the brain opiate receptor. The effect of morphine was enhanced by manganese ion in the presence of normal Na+. The responses of the cat nictitating membrane to nerve stimulation were not altered in the presence of the protein modifying reagent DTNB [5,5'-dithiobis-(2-nitrobenzoic acid)] but the effect of morphine on the adrenergic neurotransmission was diminished by DTNB with 150 mM Na+. It is postulated that the affinity of the ligands for presynaptic receptors which regulate adrenergic neurotransmission might be modified during the physiological changes in ion concentration which accompany nerve depolarization.", "contents": "Properties of the peripheral opiate receptors in the cat nictitating membrane. The noradrenaline overflow and the contractile response elicited by nerve stimulation of the muscle were inhibited by 1 micron morphine in the cat nictitating membrane. This concentration of morphine did not modify the response of the muscle to exogenous noradrenaline. The inhibitory effect of morphine was increased by low Na+ (50 mM), whereas the capacity of naloxone as antagonist to morphine was higher with 150 mM than with 50 mM Na+. These results suggest that the peripheral opiate receptors which interact with noradrenergic neurotransmission could show a sodium allosteric transformation similar to that described for the brain opiate receptor. The effect of morphine was enhanced by manganese ion in the presence of normal Na+. The responses of the cat nictitating membrane to nerve stimulation were not altered in the presence of the protein modifying reagent DTNB [5,5'-dithiobis-(2-nitrobenzoic acid)] but the effect of morphine on the adrenergic neurotransmission was diminished by DTNB with 150 mM Na+. It is postulated that the affinity of the ligands for presynaptic receptors which regulate adrenergic neurotransmission might be modified during the physiological changes in ion concentration which accompany nerve depolarization."}
{"id": "PMID:200440", "title": "Antagonism of pentobarbital-induced hormonal changes by TRH in rats.", "content": "In adult male rats, injection of TRH into a lateral ventricle of the brain 5 min prior to pentobarbital (PB) administration caused a significant dose-related inhibition of prolactin (PRL) release, in doses ranging from 500 to 5 ng. Among 8 TRH analogues devoid of thyrotropin-releasing activity, 6 were found to significantly suppress PB-induced PRL secretion at an intraventricular dose level of 10 microgram, and the 3 most effective in this respect were also able to counteract growth hormone (GH) release elicited by PB. The derivative [1,3'-DCM2]TRH was still potent enough to block PB-induced PRL secretion at an intraventricular dosage of 50 ng. The peptide ACTH 4--10 was ineffective, whereas another ACTH derivative H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH (Org 2766) reduced PRL release. TRH did not affect the increase of plasma PRL induced by acute stress. alpha-Methyl-p-tyrosine (alpha-MT) failed to influence the inhibiting effect of TRH on GH secretion but significantly reduced that on PRL release. p-Chlorophenylalanine (PCPA) completely blocked the antagonistic effect of TRH on all PB-induced hormonal changes, suggesting that serotoninergic mechanisms may be involved in the extra-pituitary effect of TRH.", "contents": "Antagonism of pentobarbital-induced hormonal changes by TRH in rats. In adult male rats, injection of TRH into a lateral ventricle of the brain 5 min prior to pentobarbital (PB) administration caused a significant dose-related inhibition of prolactin (PRL) release, in doses ranging from 500 to 5 ng. Among 8 TRH analogues devoid of thyrotropin-releasing activity, 6 were found to significantly suppress PB-induced PRL secretion at an intraventricular dose level of 10 microgram, and the 3 most effective in this respect were also able to counteract growth hormone (GH) release elicited by PB. The derivative [1,3'-DCM2]TRH was still potent enough to block PB-induced PRL secretion at an intraventricular dosage of 50 ng. The peptide ACTH 4--10 was ineffective, whereas another ACTH derivative H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH (Org 2766) reduced PRL release. TRH did not affect the increase of plasma PRL induced by acute stress. alpha-Methyl-p-tyrosine (alpha-MT) failed to influence the inhibiting effect of TRH on GH secretion but significantly reduced that on PRL release. p-Chlorophenylalanine (PCPA) completely blocked the antagonistic effect of TRH on all PB-induced hormonal changes, suggesting that serotoninergic mechanisms may be involved in the extra-pituitary effect of TRH."}
{"id": "PMID:200441", "title": "The effect of verapamil on the action of parathyroid hormone on embryonic bone in vitro.", "content": "Short term in vitro experiments showed that, added alone, verapamil inhibited both glycolysis and Ca uptake in embryonic chicken and rat bone cells. Added together with PTH, verapamil (0.02 MM) enhanced cAMP production, had no effect on lactate production, but significantly inhibited citrate, calcium and phosphate release from embryonic rat and mouse calvaria incubated under hypocalcemic conditions. The depression by verapamil of PTH-stimulated demineralization was confirmed histologically. It is concluded that in addition to cAMP, Ca plays a key role in the action of PTH on bone.", "contents": "The effect of verapamil on the action of parathyroid hormone on embryonic bone in vitro. Short term in vitro experiments showed that, added alone, verapamil inhibited both glycolysis and Ca uptake in embryonic chicken and rat bone cells. Added together with PTH, verapamil (0.02 MM) enhanced cAMP production, had no effect on lactate production, but significantly inhibited citrate, calcium and phosphate release from embryonic rat and mouse calvaria incubated under hypocalcemic conditions. The depression by verapamil of PTH-stimulated demineralization was confirmed histologically. It is concluded that in addition to cAMP, Ca plays a key role in the action of PTH on bone."}
{"id": "PMID:200442", "title": "Effect of papaverine on cyclic nucleotide levels in the isolated rat aorta.", "content": "An increase in cAMP  but no significant modification in cGMP content could be demonstrated in rat aorta strips after applying papaverine in concentrations which reduced contractile responses. Accumulation of cAMP was induced in noradrenaline-stimulated on K+-depolarized strips, under omission of external Ca2+. Thus the elevation of cAMP level preceded the reduction of contraction subsequently elicited by readdition of Ca2+. The effects could not be dissociated under the experimental conditions used here.", "contents": "Effect of papaverine on cyclic nucleotide levels in the isolated rat aorta. An increase in cAMP  but no significant modification in cGMP content could be demonstrated in rat aorta strips after applying papaverine in concentrations which reduced contractile responses. Accumulation of cAMP was induced in noradrenaline-stimulated on K+-depolarized strips, under omission of external Ca2+. Thus the elevation of cAMP level preceded the reduction of contraction subsequently elicited by readdition of Ca2+. The effects could not be dissociated under the experimental conditions used here."}
{"id": "PMID:200451", "title": "Isolation of Epstein-Barr virus from cultured cells of a patient with Hodgkin's disease.", "content": "The suspension lymphoblastoid cell line named ChSL-1 was established from the tumor node of a patient with Hodgkin's disease. The cells of this culture produce a virus with morphological and physicochemical properties of herpes viruses. Immunologic study of the isolated virus demonstrated great similarity with the Epstein-Barr virus (EBV).", "contents": "Isolation of Epstein-Barr virus from cultured cells of a patient with Hodgkin's disease. The suspension lymphoblastoid cell line named ChSL-1 was established from the tumor node of a patient with Hodgkin's disease. The cells of this culture produce a virus with morphological and physicochemical properties of herpes viruses. Immunologic study of the isolated virus demonstrated great similarity with the Epstein-Barr virus (EBV)."}
{"id": "PMID:200452", "title": "Effect of microwave radiation on cells treated with membrane-injuring substances.", "content": "WISH cells grown in vitro were pretreated with subcytotoxic concentrations of digitonin, cortisol and purified bacterial toxins -- staphylococcal beta-haemolysin or Clostridium perfringens alpha-toxin and irradiated with 3 GHz electromagnetic wave (microwaves) at the field power densities 5 or 40 mW/cm2. At 40 mW/cm2 increase in temperature of the culture medium of about 2-3 degrees C was noted, while at 5 mW/cm2 no detectable increase in temperature was found. Control and pretreated WISH cells after irradiation in the microwave field were used for evaluation of their viability, incorporation of tritiated thymidine, glycine and uridine and level of intracellular cyclic AMP. Irradiation with microwaves resulted in lowering of thymidine and glycine incorporation along with changes in the intracellular amount of cAMP (decrease in cells exposed to 5 mW/cm2 and increase in those exposed to 40 mW/cm2). Under both conditions viability of the cultures was normal. Pretreatment of cells with digitonin or purified bacterial toxins followed by irradiation with microwaves resulted in enhancement of the cytotoxic effect with lowering of cell viability, especially after exposition to power density of 40 mW/cm2. Cortisol led to decrease in 3H-glycine and 3H-uridine incorporation into WISH cells, but did not influence the reaction of the cells to microwave radiation. In view of the results presented it may be concluded that substances injuring cell membranes sensitize cell cultures to electromagnetic radiation of the microwave range and may enhance the specific (non-thermal) effect of microwaves.", "contents": "Effect of microwave radiation on cells treated with membrane-injuring substances. WISH cells grown in vitro were pretreated with subcytotoxic concentrations of digitonin, cortisol and purified bacterial toxins -- staphylococcal beta-haemolysin or Clostridium perfringens alpha-toxin and irradiated with 3 GHz electromagnetic wave (microwaves) at the field power densities 5 or 40 mW/cm2. At 40 mW/cm2 increase in temperature of the culture medium of about 2-3 degrees C was noted, while at 5 mW/cm2 no detectable increase in temperature was found. Control and pretreated WISH cells after irradiation in the microwave field were used for evaluation of their viability, incorporation of tritiated thymidine, glycine and uridine and level of intracellular cyclic AMP. Irradiation with microwaves resulted in lowering of thymidine and glycine incorporation along with changes in the intracellular amount of cAMP (decrease in cells exposed to 5 mW/cm2 and increase in those exposed to 40 mW/cm2). Under both conditions viability of the cultures was normal. Pretreatment of cells with digitonin or purified bacterial toxins followed by irradiation with microwaves resulted in enhancement of the cytotoxic effect with lowering of cell viability, especially after exposition to power density of 40 mW/cm2. Cortisol led to decrease in 3H-glycine and 3H-uridine incorporation into WISH cells, but did not influence the reaction of the cells to microwave radiation. In view of the results presented it may be concluded that substances injuring cell membranes sensitize cell cultures to electromagnetic radiation of the microwave range and may enhance the specific (non-thermal) effect of microwaves."}
{"id": "PMID:200453", "title": "Electron microscope study of thallium-induced alterations in the oligodendrocytes of the rat area postrema.", "content": "Thallotoxicosis following accidental ingestion of thallium in rodenticides and in cases of homicidal and suicidal ingestion are well documented in the literature. The mechanism of action of thallium, in particular the pathogenesis of its neurotoxic manifestations, is not entirely clear. This is the first electron microscopic investigation dealing with the effect of thallium on the oligodendrocytes of the area postrema. The area postrema is devoid of a blood-brain barrier, indicating that the hemoneural transport of thallous ions may be quite substantial in this region. Rats weighing 155-175 g were given intraperitoneal injections of 5 mg/kg thallous acetate for 7 days (35 mg/kg total dose). Following perfusion-fixation, ultrathin sections of area postrema were examined with an electron microscope. The oligodendrocytes exhibited pleomorphic vacuolated dense bodies in their perikaryon. The findings were also suggestive of the fact that either the multiplication of oligodendrocytes or their aggregation to form \"giant cell\" was operative.", "contents": "Electron microscope study of thallium-induced alterations in the oligodendrocytes of the rat area postrema. Thallotoxicosis following accidental ingestion of thallium in rodenticides and in cases of homicidal and suicidal ingestion are well documented in the literature. The mechanism of action of thallium, in particular the pathogenesis of its neurotoxic manifestations, is not entirely clear. This is the first electron microscopic investigation dealing with the effect of thallium on the oligodendrocytes of the area postrema. The area postrema is devoid of a blood-brain barrier, indicating that the hemoneural transport of thallous ions may be quite substantial in this region. Rats weighing 155-175 g were given intraperitoneal injections of 5 mg/kg thallous acetate for 7 days (35 mg/kg total dose). Following perfusion-fixation, ultrathin sections of area postrema were examined with an electron microscope. The oligodendrocytes exhibited pleomorphic vacuolated dense bodies in their perikaryon. The findings were also suggestive of the fact that either the multiplication of oligodendrocytes or their aggregation to form \"giant cell\" was operative."}
{"id": "PMID:200454", "title": "Dissolution of silicic acid from dusts of kaolin, mica and talc and its relation to their hemolytic activity. -- an in vitro study.", "content": "Hemolysis induced by native kaolin dust was found to run parallel to the amount of silicic acid dissolved from it. Native mica and talc dusts were hemolytic only to a small extent and the silicic acid dissolution from these dusts was also smaller in comparison to that of native kaolin. The proportionality between hemolysis and the amount of dissolved silicic acid was not consistently observed in the case of acid, alkali and water treated kaolin, mica and talc dusts.", "contents": "Dissolution of silicic acid from dusts of kaolin, mica and talc and its relation to their hemolytic activity. -- an in vitro study. Hemolysis induced by native kaolin dust was found to run parallel to the amount of silicic acid dissolved from it. Native mica and talc dusts were hemolytic only to a small extent and the silicic acid dissolution from these dusts was also smaller in comparison to that of native kaolin. The proportionality between hemolysis and the amount of dissolved silicic acid was not consistently observed in the case of acid, alkali and water treated kaolin, mica and talc dusts."}
{"id": "PMID:200455", "title": "Interaction of molybdate with copper(II)-histidine.", "content": "Molybdate and copper(II)-histidine form an insoluble complex of empirical formula Cu2(His)3(MoO4)2(H2O)2ESR-spectroscopy indicated that the complex had tetragonal symmetry. IR-spectroscopy showed the presence of a carboxylate anion and suggested that the molybdate ion formed an ammonium-type salt with the nitrogens of the imidazole. The complex did not form following dissociation of the protonated imidazole (above a pH of approximately 6).", "contents": "Interaction of molybdate with copper(II)-histidine. Molybdate and copper(II)-histidine form an insoluble complex of empirical formula Cu2(His)3(MoO4)2(H2O)2ESR-spectroscopy indicated that the complex had tetragonal symmetry. IR-spectroscopy showed the presence of a carboxylate anion and suggested that the molybdate ion formed an ammonium-type salt with the nitrogens of the imidazole. The complex did not form following dissociation of the protonated imidazole (above a pH of approximately 6)."}
{"id": "PMID:200456", "title": "Alterations in the phospholipid composition of Nocardia polychromogenes during growth.", "content": "The major phospholipid classes of Nocardia polychromogenes were quantitated at different stages of the growth cycle. Significant differences were observed both in the total lipid phosphorus per g (dry weight) of cells, and in the relative percentages of individual phospholipids. The total amount of lipid-phosphorus increased throughout the growth cycle. Cardiolipin and phosphoinositides contents increased with significant decrease in phosphatidyl ethanolamine and unknown phospholipids.", "contents": "Alterations in the phospholipid composition of Nocardia polychromogenes during growth. The major phospholipid classes of Nocardia polychromogenes were quantitated at different stages of the growth cycle. Significant differences were observed both in the total lipid phosphorus per g (dry weight) of cells, and in the relative percentages of individual phospholipids. The total amount of lipid-phosphorus increased throughout the growth cycle. Cardiolipin and phosphoinositides contents increased with significant decrease in phosphatidyl ethanolamine and unknown phospholipids."}
{"id": "PMID:200457", "title": "Cholesterol synthesis in freshly isolated human leukocytes.", "content": "Cholesterol synthesis has been studied in human leukocytes shortly after the isolation from healthy subjects. Not delipidated human serum reduced the cholesterol synthesis when added to the incubation medium. A similar effect was obtained when the leukocytes were incubated in the presence of physiological concentrations of low density lipoproteins.", "contents": "Cholesterol synthesis in freshly isolated human leukocytes. Cholesterol synthesis has been studied in human leukocytes shortly after the isolation from healthy subjects. Not delipidated human serum reduced the cholesterol synthesis when added to the incubation medium. A similar effect was obtained when the leukocytes were incubated in the presence of physiological concentrations of low density lipoproteins."}
{"id": "PMID:200458", "title": "Lead potentiation of endotoxin lethality in rats: lack of effect of kininase inhibition.", "content": "Although lead and SQ20881 are potent in vitro inhibitors of kininase II activity, SQ20881 does not alter the sensitivity of rats to endotoxin. These results indicate that marked changes in plasma kininase activity do not contribute to endotoxin morbidity and that kininase inhibition is not the mechanism whereby lead ions sensitize rats to endotoxin.", "contents": "Lead potentiation of endotoxin lethality in rats: lack of effect of kininase inhibition. Although lead and SQ20881 are potent in vitro inhibitors of kininase II activity, SQ20881 does not alter the sensitivity of rats to endotoxin. These results indicate that marked changes in plasma kininase activity do not contribute to endotoxin morbidity and that kininase inhibition is not the mechanism whereby lead ions sensitize rats to endotoxin."}
{"id": "PMID:200459", "title": "Corticotropin and nonshivering thermogenesis.", "content": "Chronic treatment with corticotropin led to reduced calorigenic effect of norepinephrine in cold acclimatized rats, but potentiated its effect in controls. This inhibitory effect was not due to the observed decrease in corticosterone plasma level, as it was shown by metopirone administration. It is concluded that corticotropin could have a competitive action on receptor sites mediating the calorigenic effect of norepinephrine in nonshivering thermogenesis.", "contents": "Corticotropin and nonshivering thermogenesis. Chronic treatment with corticotropin led to reduced calorigenic effect of norepinephrine in cold acclimatized rats, but potentiated its effect in controls. This inhibitory effect was not due to the observed decrease in corticosterone plasma level, as it was shown by metopirone administration. It is concluded that corticotropin could have a competitive action on receptor sites mediating the calorigenic effect of norepinephrine in nonshivering thermogenesis."}
{"id": "PMID:200460", "title": "A cholinergic modulator.", "content": "Soluble proteins obtained from presynaptic cholinergic vesicles have been tested regarding their effects to modify postsynaptic spike generation. The results suggest that these proteins (or derivatives, incl. glycopeptides) may act as modulators in increasing the effectiveness and duration of postsynaptic spike generation. They may partake in generation of homosynaptic (posttetanic) potentiation.", "contents": "A cholinergic modulator. Soluble proteins obtained from presynaptic cholinergic vesicles have been tested regarding their effects to modify postsynaptic spike generation. The results suggest that these proteins (or derivatives, incl. glycopeptides) may act as modulators in increasing the effectiveness and duration of postsynaptic spike generation. They may partake in generation of homosynaptic (posttetanic) potentiation."}
{"id": "PMID:200461", "title": "Facilitation of synaptic transmission by diazepam in a perfused frog cerebellum.", "content": "The action of diazepam on the parallel fibres-Purkinje cell synapse was studied in a perfused frog cerebellum. Diazepam facilitates the excitatory input to Purkinje cells and hence increases the inhibition produced by Purkinje cells activity.", "contents": "Facilitation of synaptic transmission by diazepam in a perfused frog cerebellum. The action of diazepam on the parallel fibres-Purkinje cell synapse was studied in a perfused frog cerebellum. Diazepam facilitates the excitatory input to Purkinje cells and hence increases the inhibition produced by Purkinje cells activity."}
{"id": "PMID:200462", "title": "Cyclic AMP in neuroblastoma, ganglioneuroma and sympathetic ganglia.", "content": "Tissue content of cyclic AMP was as much as 10 times greater in ganglioneuroma than in neuroblastoma. This high cyclic AMP in ganglioneuroma was not significantly different from that of sympathetic ganglia.", "contents": "Cyclic AMP in neuroblastoma, ganglioneuroma and sympathetic ganglia. Tissue content of cyclic AMP was as much as 10 times greater in ganglioneuroma than in neuroblastoma. This high cyclic AMP in ganglioneuroma was not significantly different from that of sympathetic ganglia."}
{"id": "PMID:200463", "title": "Effects of various hormones and adrenalectomy on the levels of amylase in rat pancreas and parotid gland.", "content": "Dexamethasone, adrenocorticotropic hormone and thyroxine increased the amylase activities in both the pancreas and the parotid gland of infant rats. After adrenalectomy, the amylase activities of the pancreas and parotid gland were about half the control levels, suggesting that both glucocorticoid and thyroxine are involved in maintaining the amylase activities in these organs.", "contents": "Effects of various hormones and adrenalectomy on the levels of amylase in rat pancreas and parotid gland. Dexamethasone, adrenocorticotropic hormone and thyroxine increased the amylase activities in both the pancreas and the parotid gland of infant rats. After adrenalectomy, the amylase activities of the pancreas and parotid gland were about half the control levels, suggesting that both glucocorticoid and thyroxine are involved in maintaining the amylase activities in these organs."}
{"id": "PMID:200469", "title": "[Research on substances with antiviral activity. VII. Activity and lipophilic of property N-alkyl-2-chloro-3-formylindole thiosemicarbazone].", "content": "Thiosemicarbazones of N-alkyl-2-chloroindole-3-carboxaldehydes were synthesized and investigated for antiviral activity against RNA virus (parainfluenza type 3, HA-I/CR-8 stock) and DNA virus (vaccinia virus, HID stock). The effect of lipophilicity on the activity against vaccinia virus was considered. Relative lipophilicities were measured by a reversed phase thin-layer chromatographic technique. The most active compound N-isopropyl-2-chloroindole-3-carboxaldehyde thiosemicarbazone appeared comparable for its activity to methisazone.", "contents": "[Research on substances with antiviral activity. VII. Activity and lipophilic of property N-alkyl-2-chloro-3-formylindole thiosemicarbazone]. Thiosemicarbazones of N-alkyl-2-chloroindole-3-carboxaldehydes were synthesized and investigated for antiviral activity against RNA virus (parainfluenza type 3, HA-I/CR-8 stock) and DNA virus (vaccinia virus, HID stock). The effect of lipophilicity on the activity against vaccinia virus was considered. Relative lipophilicities were measured by a reversed phase thin-layer chromatographic technique. The most active compound N-isopropyl-2-chloroindole-3-carboxaldehyde thiosemicarbazone appeared comparable for its activity to methisazone."}
{"id": "PMID:200470", "title": "[Chemical and pharmacologic study on pyran derivatives. IX. Synthesis of 2-dialkylaminochromones].", "content": "Under suitable conditions the reaction of phenol and N,N-dialkylethoxycarbonylacetamides, in the presence of phosphorus oxychloride, resulted in the formation of 2-dialkylaminochromones. In a similar manner, variously substituted phenols afforded 2-dialkylaminochromones with substituents in different positions of the benzene ring. Pharmacological screening of all these compounds showed that they markedly affect the CNS, activity being mainly excitatory. Decreased activity was shown by compounds with particular substituents in the positions 6,7,8 among which two products [(V e) - K 12440, (V s) - K 12420] have weak but clear anticonvulsant effect.", "contents": "[Chemical and pharmacologic study on pyran derivatives. IX. Synthesis of 2-dialkylaminochromones]. Under suitable conditions the reaction of phenol and N,N-dialkylethoxycarbonylacetamides, in the presence of phosphorus oxychloride, resulted in the formation of 2-dialkylaminochromones. In a similar manner, variously substituted phenols afforded 2-dialkylaminochromones with substituents in different positions of the benzene ring. Pharmacological screening of all these compounds showed that they markedly affect the CNS, activity being mainly excitatory. Decreased activity was shown by compounds with particular substituents in the positions 6,7,8 among which two products [(V e) - K 12440, (V s) - K 12420] have weak but clear anticonvulsant effect."}
{"id": "PMID:200466", "title": "[Electrolyte and water content in the kidney cortical sections of rats exposed to catecholamine action].", "content": "Functional significance of alpha and beta-adrenoreceptors and also possible involvement of the cyclic 3', 5'-AMP in the catecholamines regulation mechanism of the sodium and potassium ions transport in renal cortex slices of rats were studied. Epinephrine did not change the intracellular sodium and water content, but increased that of potassium in the cells. Phentolamine-a blocking agent of the alpha-adrenoreceptors--did not change the reaction of slices to epinephrine, while inderal--a beta-adrenoblocking agent-prevented accumulation of potassium by the cells occurring under the action of epinephrine. Isopropyl-nore-pinephrine reproduced the action of epinephrine on the electrolytes composition of the renal tissue. It is suggested that accumulation of postassium by the cells of the rats' renal cortex slices is consequent upon excitation of the beta-adrenoreceptors.", "contents": "[Electrolyte and water content in the kidney cortical sections of rats exposed to catecholamine action]. Functional significance of alpha and beta-adrenoreceptors and also possible involvement of the cyclic 3', 5'-AMP in the catecholamines regulation mechanism of the sodium and potassium ions transport in renal cortex slices of rats were studied. Epinephrine did not change the intracellular sodium and water content, but increased that of potassium in the cells. Phentolamine-a blocking agent of the alpha-adrenoreceptors--did not change the reaction of slices to epinephrine, while inderal--a beta-adrenoblocking agent-prevented accumulation of potassium by the cells occurring under the action of epinephrine. Isopropyl-nore-pinephrine reproduced the action of epinephrine on the electrolytes composition of the renal tissue. It is suggested that accumulation of postassium by the cells of the rats' renal cortex slices is consequent upon excitation of the beta-adrenoreceptors."}
{"id": "PMID:200471", "title": "[Preparation and pharmacological activity of N6, 02-dipivaloyl-cyclic AMP].", "content": "The synthesis of N6,O2'-dipivaloyl-cyclic AMP is described with some pharmacological tests made in comparison with the dibutyryl homolog. The two compounds proved equally active in increasing glycemia in the rabbit whereas the dipivaloyl derivative is less effective in counteracting contractions induced by imidazole in the isolated guinea-pig trachea.", "contents": "[Preparation and pharmacological activity of N6, 02-dipivaloyl-cyclic AMP]. The synthesis of N6,O2'-dipivaloyl-cyclic AMP is described with some pharmacological tests made in comparison with the dibutyryl homolog. The two compounds proved equally active in increasing glycemia in the rabbit whereas the dipivaloyl derivative is less effective in counteracting contractions induced by imidazole in the isolated guinea-pig trachea."}
{"id": "PMID:200467", "title": "[Antidiuretic activity of dithiocarbamic acid derivatives].", "content": "Chemically pure dithiocarbamates, thiuramsulphides and ethylene-bis-dithiocarbamates display a well-marked antidiuretic action. They materially reduce diuresis, natri- and kaliuresis in rats (1/5 LD(50) per 1 kg into the stomach) and in dogs (sodium N, N-diethyl-dithiocarbamate-into renal artery). Without changing the tubular reabsorption DEDTC inhibits the glomerular filtration of the dogs' kidneys. Furosemide (lasix) prevents the development of the an antidiuletic anidiuretic effect and reduction of the sodium and potassium excretion provoked in rats with DEDTC, zinc N, N', N\"-tetraethylthiuram-disulphide and ethylene-bis-dithiocarbamate. Furosemide is recommended for the treatment of acute poisonings with dithiocarbaminic acid derivatives.", "contents": "[Antidiuretic activity of dithiocarbamic acid derivatives]. Chemically pure dithiocarbamates, thiuramsulphides and ethylene-bis-dithiocarbamates display a well-marked antidiuretic action. They materially reduce diuresis, natri- and kaliuresis in rats (1/5 LD(50) per 1 kg into the stomach) and in dogs (sodium N, N-diethyl-dithiocarbamate-into renal artery). Without changing the tubular reabsorption DEDTC inhibits the glomerular filtration of the dogs' kidneys. Furosemide (lasix) prevents the development of the an antidiuletic anidiuretic effect and reduction of the sodium and potassium excretion provoked in rats with DEDTC, zinc N, N', N\"-tetraethylthiuram-disulphide and ethylene-bis-dithiocarbamate. Furosemide is recommended for the treatment of acute poisonings with dithiocarbaminic acid derivatives."}
{"id": "PMID:200468", "title": "[Effect of combinations of apressin, obsidan, diprazin, adenosine, NAD and nicotinamide on the resistance of rats to hypoxia and on carbohydrate metabolic indices].", "content": "As evidenced from experiments on rats, a combined application of apressin with obsidan and diprazine, and also of adenozine with nicotine-amidadenine-dinucleotide (NAD), as well as of adeozine with nicotine amide potentiates the protective effect of these substances in hypobaric hypoxia, increases the resistance of the animals to cerebral ischemia, brings down the excess lactate level and raises the redoz potential of the system lactic-acid-pyruvic acid in the brain of rats exposed to the effects of rarefied atmosphere.", "contents": "[Effect of combinations of apressin, obsidan, diprazin, adenosine, NAD and nicotinamide on the resistance of rats to hypoxia and on carbohydrate metabolic indices]. As evidenced from experiments on rats, a combined application of apressin with obsidan and diprazine, and also of adenozine with nicotine-amidadenine-dinucleotide (NAD), as well as of adeozine with nicotine amide potentiates the protective effect of these substances in hypobaric hypoxia, increases the resistance of the animals to cerebral ischemia, brings down the excess lactate level and raises the redoz potential of the system lactic-acid-pyruvic acid in the brain of rats exposed to the effects of rarefied atmosphere."}
{"id": "PMID:200496", "title": "[Role of the medial hypothalamus in regulating the pituitary-adrenocortical system].", "content": "In unrestrained rabbits, inhibition of ACTH release as determined by changes in plasma levels of corticosteroids, followed electrolytic lesion of the dorso-and ventromedia nuclei of the hypothalamus. Electric stimulation of the dorsal midbrain tegmentum had activated ACTH prior to lesion; after the lesion of the dorso-and ventromedial nuclei the stimulation produced no response. The dorso-and ventromedial nuclei of the hypothalamus are essential for basal and induced secretion of the ACTH.", "contents": "[Role of the medial hypothalamus in regulating the pituitary-adrenocortical system]. In unrestrained rabbits, inhibition of ACTH release as determined by changes in plasma levels of corticosteroids, followed electrolytic lesion of the dorso-and ventromedia nuclei of the hypothalamus. Electric stimulation of the dorsal midbrain tegmentum had activated ACTH prior to lesion; after the lesion of the dorso-and ventromedial nuclei the stimulation produced no response. The dorso-and ventromedial nuclei of the hypothalamus are essential for basal and induced secretion of the ACTH."}
{"id": "PMID:200506", "title": "Isolation of mutant adrenocortical tumor cells resistant to cyclic nucleotides.", "content": "A somatic cell genetic approach was used to study the role of cyclic nucleotides in adrenal steroidogenesis. 8-Bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated steroidogenesis (K'd=0.1 mM) in cultured mouse adrenocortical tumor cells (Clone Y1). In addition, 8BrcAMP inhibited Y1 cell growth and caused Y1 cell monolayers to assume a rounded morphology. As a consequence, 8BrcAMP (at concentrations greater than or equal to 0.4 mM) reduced the relative plating efficiency of Y1 cells to less than 10(-5). Y1 cells were mutagenized with ethyl methanesulfonate (300 microgram/ml) and grown in the presence of 0.4 mM 8BrcAMP. A surviving colony (8BrcAMPr-1) was shown to be resistant to growth inhibition (relative plating efficiency at 1.0 mM 8BrcAMP=50 percent)) and to morphological changes induced by 8BrcAMP. 8BrcAMPr-1 cells had diminished steroidogenic responses to cyclic nucleotides and to ACTH (less than or equal to 33 percent of maximum). In 8BrcAMP(R)-1 cells, adenylate cyclase activity remained responsive to ACTH, and cyclic AMP phosphodiesterase activity was not increased. These data suggest that 8BrcAMPr-1 cells are defective at a point common to cyclic AMP action on growth, morphology and steroidogenesis. The associated decrease in responsiveness of the steroidogenic pathway to ACTH suggests that ACTH-regulated steroidogenesis is via a cyclic nucleotide-mediated mechanism.", "contents": "Isolation of mutant adrenocortical tumor cells resistant to cyclic nucleotides. A somatic cell genetic approach was used to study the role of cyclic nucleotides in adrenal steroidogenesis. 8-Bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated steroidogenesis (K'd=0.1 mM) in cultured mouse adrenocortical tumor cells (Clone Y1). In addition, 8BrcAMP inhibited Y1 cell growth and caused Y1 cell monolayers to assume a rounded morphology. As a consequence, 8BrcAMP (at concentrations greater than or equal to 0.4 mM) reduced the relative plating efficiency of Y1 cells to less than 10(-5). Y1 cells were mutagenized with ethyl methanesulfonate (300 microgram/ml) and grown in the presence of 0.4 mM 8BrcAMP. A surviving colony (8BrcAMPr-1) was shown to be resistant to growth inhibition (relative plating efficiency at 1.0 mM 8BrcAMP=50 percent)) and to morphological changes induced by 8BrcAMP. 8BrcAMPr-1 cells had diminished steroidogenic responses to cyclic nucleotides and to ACTH (less than or equal to 33 percent of maximum). In 8BrcAMP(R)-1 cells, adenylate cyclase activity remained responsive to ACTH, and cyclic AMP phosphodiesterase activity was not increased. These data suggest that 8BrcAMPr-1 cells are defective at a point common to cyclic AMP action on growth, morphology and steroidogenesis. The associated decrease in responsiveness of the steroidogenic pathway to ACTH suggests that ACTH-regulated steroidogenesis is via a cyclic nucleotide-mediated mechanism."}
{"id": "PMID:200507", "title": "Discontinuity of thyroid gland response to hormonal stimulation: effect of TSH and cAMP on iodide organification.", "content": "The action of TSH on the process of iodide organification was studied in rat thyroid glands under different experimental in vitro incubation conditions. The effects on glands of both short and prolonged exposure to TSH were evaluated using two different procedures: continuous and pulse labelling of thyroids with radioactive iodide. It was demonstrated that during prolonged contact with thyroid cells, TSH stimulates iodide organification periodically. This periodic effect is cyclic and is composed of a stimulatory and an inhibitory phase. Each cycle lasts 30-45 min, and several cycles follow one another in a regular manner. Furthermore, it has been shown that the periodic effect of THS is due to an intrinsic property of the thyroid cell to respond in a cyclic manner to hormonal stimulation. TSH stimulated the accumulation of organic iodide only when introduced at a precise phase of the cycle. The same type of discontinuous thyroid cell response was obtained when TSH was replaced by its intracellular mediator, cAMP. This indicates that the initiation of the cyclic response to hormonal stimulation is localized at the steps after that of cAMP formation. It seems, therefore, that this cyclic response of thyroid glands is not related to the recently observed phenomenon of desensitization. This phenomenon, characterized by the development of resistance in many target organs and cells toward their respective hormonal stimulators, is due to modifications in steps preceding those of cAMP formation. The discontinuity of thyroid gland response to both TSH and cAMP described in this work seems to be a new phenomenon, whose physiological significance and possible molecular mechanisms are discussed.", "contents": "Discontinuity of thyroid gland response to hormonal stimulation: effect of TSH and cAMP on iodide organification. The action of TSH on the process of iodide organification was studied in rat thyroid glands under different experimental in vitro incubation conditions. The effects on glands of both short and prolonged exposure to TSH were evaluated using two different procedures: continuous and pulse labelling of thyroids with radioactive iodide. It was demonstrated that during prolonged contact with thyroid cells, TSH stimulates iodide organification periodically. This periodic effect is cyclic and is composed of a stimulatory and an inhibitory phase. Each cycle lasts 30-45 min, and several cycles follow one another in a regular manner. Furthermore, it has been shown that the periodic effect of THS is due to an intrinsic property of the thyroid cell to respond in a cyclic manner to hormonal stimulation. TSH stimulated the accumulation of organic iodide only when introduced at a precise phase of the cycle. The same type of discontinuous thyroid cell response was obtained when TSH was replaced by its intracellular mediator, cAMP. This indicates that the initiation of the cyclic response to hormonal stimulation is localized at the steps after that of cAMP formation. It seems, therefore, that this cyclic response of thyroid glands is not related to the recently observed phenomenon of desensitization. This phenomenon, characterized by the development of resistance in many target organs and cells toward their respective hormonal stimulators, is due to modifications in steps preceding those of cAMP formation. The discontinuity of thyroid gland response to both TSH and cAMP described in this work seems to be a new phenomenon, whose physiological significance and possible molecular mechanisms are discussed."}
{"id": "PMID:200508", "title": "Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: a search for the mechanism of action.", "content": "Cultures of granulosa cells from immature hypophysectomized DES-treated rats were unable to maintain progestin production of more than 48 h in medium without hormone supplementation or in the presence of FSH only. Production of progestin (20alpha-dihydroprogesterone, as measured by radioimmunoassay) remained unimpaired in the presence of androstenedione (Ad) and was markedly increased in the presence of both Ad and FSH. The combined treatment with FSH and Ad during the first 48 h of culture brought about persistent changes in the cultured cells, since progestin accumulation did not decline upon subsequent removal of these hormones during days 3 and 4 of culture. Dibutyryl cyclic AMP (DBC) was able to mimic the changes in steroidogenic capability induced by the combined action of FSH and Ad. The extent of [125I]-FSH binding, FSH-stimulable cAMP accumulation and cyclic 3',5'-nucleotide phosphodiesterase activity were not affected by addition of Ad to the culture medium. Ad synergized with DBC in the stimulation of progestin accumulation in granulosa cell cultures. It is suggested that androgen acts at a step in the regulation of progestin biosynthesis distal to cAMP production.", "contents": "Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: a search for the mechanism of action. Cultures of granulosa cells from immature hypophysectomized DES-treated rats were unable to maintain progestin production of more than 48 h in medium without hormone supplementation or in the presence of FSH only. Production of progestin (20alpha-dihydroprogesterone, as measured by radioimmunoassay) remained unimpaired in the presence of androstenedione (Ad) and was markedly increased in the presence of both Ad and FSH. The combined treatment with FSH and Ad during the first 48 h of culture brought about persistent changes in the cultured cells, since progestin accumulation did not decline upon subsequent removal of these hormones during days 3 and 4 of culture. Dibutyryl cyclic AMP (DBC) was able to mimic the changes in steroidogenic capability induced by the combined action of FSH and Ad. The extent of [125I]-FSH binding, FSH-stimulable cAMP accumulation and cyclic 3',5'-nucleotide phosphodiesterase activity were not affected by addition of Ad to the culture medium. Ad synergized with DBC in the stimulation of progestin accumulation in granulosa cell cultures. It is suggested that androgen acts at a step in the regulation of progestin biosynthesis distal to cAMP production."}
{"id": "PMID:200509", "title": "Biological and immunological properties of tritiated salmon calcitonin.", "content": "Tritiated salmon calcitonin was prepared by methylation of the free amino groups using tritiated sodium borohydride as precursor. Specific radioactivity was measured in competitive inhibition studies with specific anticalcitonin antibodies or tubular membranes as binding sites for calcitonin. The value observed, approx. 4 Ci/mmol, corresponded to methylation of one third of the available N-H bonds. Tritiated calcitonin prepared in this way retained full biological activity as assessed in vitro by stimulation of adenylate cyclase and in vivo by rat bioassay. Tritiated calcitonin specifically bound to isolated renal cells and nonspecific binding did not exceed 10% of total binding. Equilibrium was obtained after 15 min incubation. The hormone-receptor complex could be dissociated in the presence of an excess of unlabelled calcitonin. This data shows that tritiated calcitonin can be used in metabolic and receptor studies.", "contents": "Biological and immunological properties of tritiated salmon calcitonin. Tritiated salmon calcitonin was prepared by methylation of the free amino groups using tritiated sodium borohydride as precursor. Specific radioactivity was measured in competitive inhibition studies with specific anticalcitonin antibodies or tubular membranes as binding sites for calcitonin. The value observed, approx. 4 Ci/mmol, corresponded to methylation of one third of the available N-H bonds. Tritiated calcitonin prepared in this way retained full biological activity as assessed in vitro by stimulation of adenylate cyclase and in vivo by rat bioassay. Tritiated calcitonin specifically bound to isolated renal cells and nonspecific binding did not exceed 10% of total binding. Equilibrium was obtained after 15 min incubation. The hormone-receptor complex could be dissociated in the presence of an excess of unlabelled calcitonin. This data shows that tritiated calcitonin can be used in metabolic and receptor studies."}
{"id": "PMID:200510", "title": "Steroid and FSH action on LH receptors and LH-sensitive testicular responsiveness during sexual maturation of the rat.", "content": "This study examines the effect of FSH, testosterone and estradiol on testicular LH receptors and in vitro testicular responsiveness to LH in immature rats under various conditions. FSH treatment of 15-day-old immature rats significantly increased the number of LH receptors but did not alter testicular responsiveness. FSH treatment of hypophysectomized immature rats increased the number of LH receptors and markedly increased testicular responsiveness. Treatment of hypophysectomized rats with testosterone proprionate for 4 days, followed by a 5-day treatment with FSH, enhanced the effect of FSH on the number of LH receptors but did not increase the effect of FSH on testicular responsiveness. In contrast, treatment with estradiol for 4 days before FSH treatment had no effect on the FSH-induced increase in LH receptors but completely inhibited the FSH-induced increase in testicular responsiveness. These observations suggest that during male sexual maturation (1) regulation of LH receptors is distinct from regulation of testicular responsiveness to LH, (2) estradiol may be a factor in the regulation of testicular responsiveness to LH, and (3) testosterone may enhance the FSH-induced increase of LH receptors.", "contents": "Steroid and FSH action on LH receptors and LH-sensitive testicular responsiveness during sexual maturation of the rat. This study examines the effect of FSH, testosterone and estradiol on testicular LH receptors and in vitro testicular responsiveness to LH in immature rats under various conditions. FSH treatment of 15-day-old immature rats significantly increased the number of LH receptors but did not alter testicular responsiveness. FSH treatment of hypophysectomized immature rats increased the number of LH receptors and markedly increased testicular responsiveness. Treatment of hypophysectomized rats with testosterone proprionate for 4 days, followed by a 5-day treatment with FSH, enhanced the effect of FSH on the number of LH receptors but did not increase the effect of FSH on testicular responsiveness. In contrast, treatment with estradiol for 4 days before FSH treatment had no effect on the FSH-induced increase in LH receptors but completely inhibited the FSH-induced increase in testicular responsiveness. These observations suggest that during male sexual maturation (1) regulation of LH receptors is distinct from regulation of testicular responsiveness to LH, (2) estradiol may be a factor in the regulation of testicular responsiveness to LH, and (3) testosterone may enhance the FSH-induced increase of LH receptors."}
{"id": "PMID:200511", "title": "Hormone receptors: VI. On the nature of the binding of glucagon and insulin to human circulating mononuclear leukocytes.", "content": "Several characteristics of the binding of insulin and glucagon to human circulating mononuclear leukocytes have been studied. Functional analysis (latex bead ingestion) revealed that cell mixtures, as prepared according to Boyum and used generally in studies of insulin resistance in humans, consist of 20-29% phagocytic monocytes, with the remainder being lymphocytes. Partial separation of monocytes from lymphocytes on columns of Sephadex G-10, followed by correlation of insulin binding with cell type, confirms that the monocyte is the binding species. Insulin influenced neither glucose uptake nor the further conversion of glucose to lipids and CO2 by the leukocytes. The transport of alpha-aminoisobutyrate, a nonmetabolizable amino acid, into these cells was also unaffected by insulin. Monocyte/lymphocyte mixtures specifically bound glucagon and prostaglandin E1. At physiological concentrations of these hormones, steady states were reached in 15 min and 45 min, respectively. In contrast to the 8-10-fold increases in cellular cyclic AMP produced by prostaglandins, the effect of glucagon was very small but apparently real. Under appropriate preincubation conditions, sodium azide and iodoacetamide inhibited phagocytosis and insulin binding in parallel. The binding of glucagon was unaffected by these agents. Although both antimycin A and actinomycin D inhibited phagocytosis of the monocytes, only the former inhibited insulin binding; there was only a slight effect on glucagon binding. We would conclude that the binding of insulin to human circulating monocytes, although reflective of insulin resistance in diabetes mellitus and obesity, may not be to traditional receptors. In contrast, the binding of glucagon to lymphocyte/monocyte mixtures may be to function-linked receptors.", "contents": "Hormone receptors: VI. On the nature of the binding of glucagon and insulin to human circulating mononuclear leukocytes. Several characteristics of the binding of insulin and glucagon to human circulating mononuclear leukocytes have been studied. Functional analysis (latex bead ingestion) revealed that cell mixtures, as prepared according to Boyum and used generally in studies of insulin resistance in humans, consist of 20-29% phagocytic monocytes, with the remainder being lymphocytes. Partial separation of monocytes from lymphocytes on columns of Sephadex G-10, followed by correlation of insulin binding with cell type, confirms that the monocyte is the binding species. Insulin influenced neither glucose uptake nor the further conversion of glucose to lipids and CO2 by the leukocytes. The transport of alpha-aminoisobutyrate, a nonmetabolizable amino acid, into these cells was also unaffected by insulin. Monocyte/lymphocyte mixtures specifically bound glucagon and prostaglandin E1. At physiological concentrations of these hormones, steady states were reached in 15 min and 45 min, respectively. In contrast to the 8-10-fold increases in cellular cyclic AMP produced by prostaglandins, the effect of glucagon was very small but apparently real. Under appropriate preincubation conditions, sodium azide and iodoacetamide inhibited phagocytosis and insulin binding in parallel. The binding of glucagon was unaffected by these agents. Although both antimycin A and actinomycin D inhibited phagocytosis of the monocytes, only the former inhibited insulin binding; there was only a slight effect on glucagon binding. We would conclude that the binding of insulin to human circulating monocytes, although reflective of insulin resistance in diabetes mellitus and obesity, may not be to traditional receptors. In contrast, the binding of glucagon to lymphocyte/monocyte mixtures may be to function-linked receptors."}
{"id": "PMID:200524", "title": "Increased spontaneous mitotic segregation in MMS-sensitive mutants of Saccharomyces cerevisiae.", "content": "Methyl methanesulfonate (MMS)-sensitive mutants of Saccharomyces cerevisiae belonging to four different complementation groups, when homozygous, increase the rate of spontaneous mitotic segregation to canavanine resistance from heterozygous sensitive (canr/+) diploids by 13-to 170-fold. The mms8-1 mutant is MMS and X-ray sensitive and increases the rate of spontaneous mitotic segregation 170-fold. The mms9-1 and mms13-1 mutants are sensitive to X rays and UV, respectively, in addition of MMS, and increase the rate of spontaneous mitotic segregation by 13-fold and 85-fold, respectively. The mutant mms21-1 is sensitive to MMS, X rays and UV and increases the rate of spontaneous mitotic segregation 23-fold.", "contents": "Increased spontaneous mitotic segregation in MMS-sensitive mutants of Saccharomyces cerevisiae. Methyl methanesulfonate (MMS)-sensitive mutants of Saccharomyces cerevisiae belonging to four different complementation groups, when homozygous, increase the rate of spontaneous mitotic segregation to canavanine resistance from heterozygous sensitive (canr/+) diploids by 13-to 170-fold. The mms8-1 mutant is MMS and X-ray sensitive and increases the rate of spontaneous mitotic segregation 170-fold. The mms9-1 and mms13-1 mutants are sensitive to X rays and UV, respectively, in addition of MMS, and increase the rate of spontaneous mitotic segregation by 13-fold and 85-fold, respectively. The mutant mms21-1 is sensitive to MMS, X rays and UV and increases the rate of spontaneous mitotic segregation 23-fold."}
{"id": "PMID:200525", "title": "Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. I. Recessive lethal mutations.", "content": "The efficiency of the adult feeding method for EMS treatment in Drosophila melanogaster was studied by measuring the frequency of induced recessive lethals on the second chromosome. The treatment was most effective when mature spermatozoa or spermatids were treated and was much less effective on earlier stages. The number of mutations induced was proportional to the concentration except at the highest doses. The recessive lethal rate was estimated to be about 0.012 per second chromosome per 10(-4) M. In addition, about 0.004-0.005 recessive lethals per 10(-4) M were found in a later generation in chromosomes that had not shown the lethal effect in the previous generation. When the experiments are done in a consistent manner and gametes treated as mature sperm or spermatids are sampled, the results are highly reproducible. However, modifications of the procedure, such as starvation before EMS treatment, can considerably alter the effectiveness of the mutagen.", "contents": "Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. I. Recessive lethal mutations. The efficiency of the adult feeding method for EMS treatment in Drosophila melanogaster was studied by measuring the frequency of induced recessive lethals on the second chromosome. The treatment was most effective when mature spermatozoa or spermatids were treated and was much less effective on earlier stages. The number of mutations induced was proportional to the concentration except at the highest doses. The recessive lethal rate was estimated to be about 0.012 per second chromosome per 10(-4) M. In addition, about 0.004-0.005 recessive lethals per 10(-4) M were found in a later generation in chromosomes that had not shown the lethal effect in the previous generation. When the experiments are done in a consistent manner and gametes treated as mature sperm or spermatids are sampled, the results are highly reproducible. However, modifications of the procedure, such as starvation before EMS treatment, can considerably alter the effectiveness of the mutagen."}
{"id": "PMID:200526", "title": "Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. II. Homozygous effect of polygenic mutations.", "content": "Polygenic mutations affecting viability were accumulated on the second chromosome of Drosophila melanogaster by treating flies with EMS in successive generations. The treated chromosomes were later made homozygous and tested for their effects on viability by comparison of the frequency of such homozygotes with that of other genotypes in the same culture. The treated wild-type chromosomes were kept heterozygous in Pm/+ males by mating individual males in successive generations to Cy/Pm females. The number of generations of accumulation was 1 to 30 generations, depending on the concentration of EMS. A similar experiment for spontaneous polygenic mutations was also conducted by accumulating mutations for 40 generations. The lower limit of the spontaneous mutation rate of viability polygenes is estimated to be 0.06 per second chromosome per generation, which is about 12 times as high as the spontaneous recessive lethal mutation rate, 0.005. EMS-induced polygenic mutations increase linearly with the number of treated generations and with the concentration of EMS. The minimum mutation rate of viability polygenes is about 0.017 per 10(-4)m, which is only slightly larger than the lethal rate of 0.013 per 10(-4) m. The maximum estimate of the viability reduction of a single mutant is about 6 to 10 percent of the normal viability. The data are consistent with a constant average effect per mutant at all concentrations, but this is about three times as high as that for spontaneous mutants. It is obvious that one can obtain only a lower limit for the mutation rate, since some mutants may have effects so near to zero that they cannot be detected. The possibility of measuring something other than the lower limit is discussed. The ratio of the load due to detrimental mutants to that caused by lethals, the D/L ratio, is about 0.2 to 0.3 for EMS-induced mutants, as compared to about 0.5 for spontaneous mutants. This is to be expected if EMS treatment produces a large fraction of small deletions and other chromosome rearrangements which are more likely to be lethal.", "contents": "Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. II. Homozygous effect of polygenic mutations. Polygenic mutations affecting viability were accumulated on the second chromosome of Drosophila melanogaster by treating flies with EMS in successive generations. The treated chromosomes were later made homozygous and tested for their effects on viability by comparison of the frequency of such homozygotes with that of other genotypes in the same culture. The treated wild-type chromosomes were kept heterozygous in Pm/+ males by mating individual males in successive generations to Cy/Pm females. The number of generations of accumulation was 1 to 30 generations, depending on the concentration of EMS. A similar experiment for spontaneous polygenic mutations was also conducted by accumulating mutations for 40 generations. The lower limit of the spontaneous mutation rate of viability polygenes is estimated to be 0.06 per second chromosome per generation, which is about 12 times as high as the spontaneous recessive lethal mutation rate, 0.005. EMS-induced polygenic mutations increase linearly with the number of treated generations and with the concentration of EMS. The minimum mutation rate of viability polygenes is about 0.017 per 10(-4)m, which is only slightly larger than the lethal rate of 0.013 per 10(-4) m. The maximum estimate of the viability reduction of a single mutant is about 6 to 10 percent of the normal viability. The data are consistent with a constant average effect per mutant at all concentrations, but this is about three times as high as that for spontaneous mutants. It is obvious that one can obtain only a lower limit for the mutation rate, since some mutants may have effects so near to zero that they cannot be detected. The possibility of measuring something other than the lower limit is discussed. The ratio of the load due to detrimental mutants to that caused by lethals, the D/L ratio, is about 0.2 to 0.3 for EMS-induced mutants, as compared to about 0.5 for spontaneous mutants. This is to be expected if EMS treatment produces a large fraction of small deletions and other chromosome rearrangements which are more likely to be lethal."}
{"id": "PMID:200527", "title": "Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. III. Heterozygous effect of polygenic mutations.", "content": "Spontaneous and EMS-induced mutations were accumulated for several generations on the second chromosome of Drosophila melanogaster by keeping this chromosome heterozygous under conditions of minimal natural selection. This article reports studies of heterozygous effects of these mutants.--Both lethal and mildly deleterious mutants have a deleterious heterozygous effect. There was no discernible difference between heterozygotes in which all the mutants were on one chromosome and those where the mutants were distributed over both homologs; thus the coupling-repulsion effect of MUKAI and YAMAZAKI (1964, 1968) is not confirmed. The spontaneous polygenic mutants have a dominance of 0.4 to 0.5, and the same value is found at very low EMS doses. However, the value at higher EMS doses is only about half as high. Since the low doses have a large fraction of spontaneous mutants, the dominance of EMS mutants is less, in the range 0.1 to 0.3, but still larger than for lethals.", "contents": "Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. III. Heterozygous effect of polygenic mutations. Spontaneous and EMS-induced mutations were accumulated for several generations on the second chromosome of Drosophila melanogaster by keeping this chromosome heterozygous under conditions of minimal natural selection. This article reports studies of heterozygous effects of these mutants.--Both lethal and mildly deleterious mutants have a deleterious heterozygous effect. There was no discernible difference between heterozygotes in which all the mutants were on one chromosome and those where the mutants were distributed over both homologs; thus the coupling-repulsion effect of MUKAI and YAMAZAKI (1964, 1968) is not confirmed. The spontaneous polygenic mutants have a dominance of 0.4 to 0.5, and the same value is found at very low EMS doses. However, the value at higher EMS doses is only about half as high. Since the low doses have a large fraction of spontaneous mutants, the dominance of EMS mutants is less, in the range 0.1 to 0.3, but still larger than for lethals."}
{"id": "PMID:200533", "title": "[Antidotes in acute poisonings].", "content": "Inhalation of dexamethazone (Auxiloson) prohibits a toxic edema of the lungs after poisoning with irritants. Poisoning with methanol is to be treated with ethanol trisbuffer and tetrahydrofolic acid (Folsan). \"Solvents\" should be \"bound\" in paraffinum liquidum in order to prohibit their absorption. Poisoning with organophosphates is to be treated with high doses of atropine and with the reactivator obidoxime (Toxogonin). Cyanide poisoningis are to be treated with 4-dimethylamino-phenol (DMAP) and sodium thiosulfate. In methemoglobin-poisoning the reduction of ferrihemoglobin is accelerated when toluidine-blue is applied intravenously.", "contents": "[Antidotes in acute poisonings]. Inhalation of dexamethazone (Auxiloson) prohibits a toxic edema of the lungs after poisoning with irritants. Poisoning with methanol is to be treated with ethanol trisbuffer and tetrahydrofolic acid (Folsan). \"Solvents\" should be \"bound\" in paraffinum liquidum in order to prohibit their absorption. Poisoning with organophosphates is to be treated with high doses of atropine and with the reactivator obidoxime (Toxogonin). Cyanide poisoningis are to be treated with 4-dimethylamino-phenol (DMAP) and sodium thiosulfate. In methemoglobin-poisoning the reduction of ferrihemoglobin is accelerated when toluidine-blue is applied intravenously."}
{"id": "PMID:200535", "title": "Insulin release from collagenase-isolated islets of rat pancreas in the presence of cyclic AMP and somatostatin.", "content": "In order to study the role of cyclic AMP in the inhibition by somatostatin of glucose-induced insulin release, the effect of somatostatin on the potentiation by dibutyryl-cyclic AMP (db-cAMP) of insulin release from isolated pancreatic islets of rats was examined. Isolated islets were obtained from the rat pancreas by the collagenase method. Ten islets were incubated for periods of 30 min in Krebs-Ringer bicarbonate buffer containg albumin and glucose 2.0 mg/ml in the presence or absence of somatostatin (1 microgram/ml or 100 ng/ml) and/or db-cAMP 1 mM. Glucose-induced insulin release was reduced by somatostatin in concentrations of 1 microgram/ml. Somatostatin in a concentration of 100 ng/ml significantly abolished the potentiation by db-cAMP of insulin release (p less than 0;01), in spite of exerting no inhibition of glucose-induced insulin release. However, in the presence of theophylline 5 mM, somatostatin 100 ng/ml did not show that inhibitory effect on the potentiated insulin release.", "contents": "Insulin release from collagenase-isolated islets of rat pancreas in the presence of cyclic AMP and somatostatin. In order to study the role of cyclic AMP in the inhibition by somatostatin of glucose-induced insulin release, the effect of somatostatin on the potentiation by dibutyryl-cyclic AMP (db-cAMP) of insulin release from isolated pancreatic islets of rats was examined. Isolated islets were obtained from the rat pancreas by the collagenase method. Ten islets were incubated for periods of 30 min in Krebs-Ringer bicarbonate buffer containg albumin and glucose 2.0 mg/ml in the presence or absence of somatostatin (1 microgram/ml or 100 ng/ml) and/or db-cAMP 1 mM. Glucose-induced insulin release was reduced by somatostatin in concentrations of 1 microgram/ml. Somatostatin in a concentration of 100 ng/ml significantly abolished the potentiation by db-cAMP of insulin release (p less than 0;01), in spite of exerting no inhibition of glucose-induced insulin release. However, in the presence of theophylline 5 mM, somatostatin 100 ng/ml did not show that inhibitory effect on the potentiated insulin release."}
{"id": "PMID:200536", "title": "Glycogen metabolism and cyclic AMP levels in isolated islets of lean and genetically obese mice.", "content": "The levels of glycogen and cyclic AMP, incorporation of glucose into glycogen and activities of glycogen synthetase and phosphorylase were determined in pancreatic islets isolated from genetically obese mice and their lean litter-mates. Islets from obese mice had elevated glycogen levels, increased phosphorylase activity and an increased amount of glycogen synthetase in the physiologically more effective I-form, indicating an increased turnover of glycogen. There was no significant difference in cyclic AMP levels between islets of lean and obese mice, but inhibition of phosphodiesterase or stimulation of adenyl cyclase increased cyclic AMP levels more in obese than in lean mouse islets, indicating a more rapid turnover of cyclic AMP in the former. It is suggested that cyclic AMP stimulated phosphorolytic breakdown of glycogen may be one of the mechanisms responsible for the increased insulin secretory response to glucose observed in islets from genetically obese mice.", "contents": "Glycogen metabolism and cyclic AMP levels in isolated islets of lean and genetically obese mice. The levels of glycogen and cyclic AMP, incorporation of glucose into glycogen and activities of glycogen synthetase and phosphorylase were determined in pancreatic islets isolated from genetically obese mice and their lean litter-mates. Islets from obese mice had elevated glycogen levels, increased phosphorylase activity and an increased amount of glycogen synthetase in the physiologically more effective I-form, indicating an increased turnover of glycogen. There was no significant difference in cyclic AMP levels between islets of lean and obese mice, but inhibition of phosphodiesterase or stimulation of adenyl cyclase increased cyclic AMP levels more in obese than in lean mouse islets, indicating a more rapid turnover of cyclic AMP in the former. It is suggested that cyclic AMP stimulated phosphorolytic breakdown of glycogen may be one of the mechanisms responsible for the increased insulin secretory response to glucose observed in islets from genetically obese mice."}
{"id": "PMID:200539", "title": "Effects of hypothalamic extract and corticosterone on incorporation of 14C-phenylalanine into newly synthesized ACTH-like protein in vitro.", "content": "The purpose of the present experiments was firstly, to examine the efficacy of the oxycellulose-Amberlite CG-50 extraction procedure for the isolation of rat pituitary ACTH and secondly, to study the effects of both hypothalamic extract and corticosterone on the synthesis of rat pituitary ACTH. Briefly, 'cold' rat pituitary ACTH was monitored by bioassay in each step of the isolation procedure as a function of corticosterone stimulation in incubated adrenal slices. Labeled ACTH was isolated from rat pituitaries previously incubated in vitro and obtained from adrenalectomized animals and cortisone acetate treated animals to provide further data to substantiate that the labeled isolated protein contained ACTH. Cold ACTH was detected in two purified fractions (oxycellulose and Amberlite CG-50). Adrenalectomy stimulated and cortisone acetate suppressed the incorporation of 14C-phenylalaine into the ACTH-like protein in these two fractions. A continuously increasing uptake of the label into ACTH-like protein in the isolated fractions occurred with time providing evidence that de novo synthesis had taken place. Corticosterone inhibited ACTH synthesis at both 10(-4) and 10(-6) M, whereas, hypothalamic stalk median eminence (HSME) caused a significant, but not dose-related, increase in ACTH synthesis with 3/5, 1, and 2 HSME equivalents added.", "contents": "Effects of hypothalamic extract and corticosterone on incorporation of 14C-phenylalanine into newly synthesized ACTH-like protein in vitro. The purpose of the present experiments was firstly, to examine the efficacy of the oxycellulose-Amberlite CG-50 extraction procedure for the isolation of rat pituitary ACTH and secondly, to study the effects of both hypothalamic extract and corticosterone on the synthesis of rat pituitary ACTH. Briefly, 'cold' rat pituitary ACTH was monitored by bioassay in each step of the isolation procedure as a function of corticosterone stimulation in incubated adrenal slices. Labeled ACTH was isolated from rat pituitaries previously incubated in vitro and obtained from adrenalectomized animals and cortisone acetate treated animals to provide further data to substantiate that the labeled isolated protein contained ACTH. Cold ACTH was detected in two purified fractions (oxycellulose and Amberlite CG-50). Adrenalectomy stimulated and cortisone acetate suppressed the incorporation of 14C-phenylalaine into the ACTH-like protein in these two fractions. A continuously increasing uptake of the label into ACTH-like protein in the isolated fractions occurred with time providing evidence that de novo synthesis had taken place. Corticosterone inhibited ACTH synthesis at both 10(-4) and 10(-6) M, whereas, hypothalamic stalk median eminence (HSME) caused a significant, but not dose-related, increase in ACTH synthesis with 3/5, 1, and 2 HSME equivalents added."}
{"id": "PMID:200540", "title": "On the molecular weight of mitochondrially synthesized subunits of rat liver cytochrome oxidase.", "content": "The subunit composition of cytochrome c oxidase from rat liver mitochondria was studied by dodecylsulfate polyacrylamide gel electrophoresis. The apparent molecular weight of the seven subunits are in reasonable agreement with published data on cytochrome c oxidase subunits from other sources. Two additional subunits were found if the electrophoresis was performed with 8m urea, due to splitting of the smallest subunit. Performic acid oxidation of the isolated subunits I and II increased the apparent molecular weights from 38000 to 48000 and from 24500 to 29000, respectively, accompained by a normalization of the anomalous behaviour of subunit I in the Ferguson plot. It is suggested that performic acid, by splitting extremely inaccessible disulfide bridges, mediates full complexing of the subunits by dodecylsulfate, thus permitting the determination of the real molecular weights by dodecylsulfate polyacrylamide gel electrophoresis.", "contents": "On the molecular weight of mitochondrially synthesized subunits of rat liver cytochrome oxidase. The subunit composition of cytochrome c oxidase from rat liver mitochondria was studied by dodecylsulfate polyacrylamide gel electrophoresis. The apparent molecular weight of the seven subunits are in reasonable agreement with published data on cytochrome c oxidase subunits from other sources. Two additional subunits were found if the electrophoresis was performed with 8m urea, due to splitting of the smallest subunit. Performic acid oxidation of the isolated subunits I and II increased the apparent molecular weights from 38000 to 48000 and from 24500 to 29000, respectively, accompained by a normalization of the anomalous behaviour of subunit I in the Ferguson plot. It is suggested that performic acid, by splitting extremely inaccessible disulfide bridges, mediates full complexing of the subunits by dodecylsulfate, thus permitting the determination of the real molecular weights by dodecylsulfate polyacrylamide gel electrophoresis."}
{"id": "PMID:200542", "title": "Inactivation of pyruvate kinase type M2 from chicken liver by phosphorylation, catalyzed by a cAMP-independent protein kinase.", "content": "A cAMP-independent protein kinase from chicken liver phosphorylated and inactivated pyruvate kinase type M2 from the same tissue. Complete inactivation was reached when 4 mol of phosphate were incorporated/mol of tetrameric pyruvate kinase. The protein kinase bound with high affinity to pyruvate kinase type M2 (Km value for pyruvate kinase = 6 X 10(-10)M; it phosphorylated phosvitin and casein but not histones, ATP and GTP were substrates. The differences between the properties of this protein kinase in the interconversion of pyruvate kinase and that described previously are discussed.", "contents": "Inactivation of pyruvate kinase type M2 from chicken liver by phosphorylation, catalyzed by a cAMP-independent protein kinase. A cAMP-independent protein kinase from chicken liver phosphorylated and inactivated pyruvate kinase type M2 from the same tissue. Complete inactivation was reached when 4 mol of phosphate were incorporated/mol of tetrameric pyruvate kinase. The protein kinase bound with high affinity to pyruvate kinase type M2 (Km value for pyruvate kinase = 6 X 10(-10)M; it phosphorylated phosvitin and casein but not histones, ATP and GTP were substrates. The differences between the properties of this protein kinase in the interconversion of pyruvate kinase and that described previously are discussed."}
{"id": "PMID:200544", "title": "Irreversible inhibition of hypoxanthine phosphoribosyltransferase. Further studies on the specificity of periodate-oxidized GMP.", "content": "Inactivation of hypoxanthine phosphoribosyltransferase caused by periodate-oxidized GMP is irreversible, even under the conditions of polyacrylamide gel electrophoresis and during affinity chromatography on GMP-Sepharose. Partial binding of the inhibitor to the enzyme protein can be demonstrated on dodecyl sulfate gel electrophoresis: The substrate, phosphoribosyl diphosphate in the presence of Mg2, and the product GMP protect the enzyme against inactivation. Periodate-oxidized GMP, AMP and oxidized purine nucleosides do not influence ribosephosphate pyrophosphokinase, 5'-nucleotidase, purine-nucleoside phosphorylase and guanylate kinase. A variety of other purine nucleosides and nucleotides, tested in their periodateoxidized form, do not lead to a compound comparable or superior to oxidized GMP in its effect on hypoxanthine phosphoribosyltransferase. In an erythrocyte system it is clearly demonstrated that oxidized GMP cannot act across an intact cell membrane.", "contents": "Irreversible inhibition of hypoxanthine phosphoribosyltransferase. Further studies on the specificity of periodate-oxidized GMP. Inactivation of hypoxanthine phosphoribosyltransferase caused by periodate-oxidized GMP is irreversible, even under the conditions of polyacrylamide gel electrophoresis and during affinity chromatography on GMP-Sepharose. Partial binding of the inhibitor to the enzyme protein can be demonstrated on dodecyl sulfate gel electrophoresis: The substrate, phosphoribosyl diphosphate in the presence of Mg2, and the product GMP protect the enzyme against inactivation. Periodate-oxidized GMP, AMP and oxidized purine nucleosides do not influence ribosephosphate pyrophosphokinase, 5'-nucleotidase, purine-nucleoside phosphorylase and guanylate kinase. A variety of other purine nucleosides and nucleotides, tested in their periodateoxidized form, do not lead to a compound comparable or superior to oxidized GMP in its effect on hypoxanthine phosphoribosyltransferase. In an erythrocyte system it is clearly demonstrated that oxidized GMP cannot act across an intact cell membrane."}
{"id": "PMID:200545", "title": "Structure of a cytochrome b-c 1 complex from Saccharomyces cerevisiae YF.", "content": "1) An isolation and purification procedure is reported for an active cytochrome b-c1 complex from Saccharomyces cerevisiae. The complex acts as an antimycin A-sensitive duroquinone-cytochrome c reductase and contains cytochromes b and c1 at a concentration of 8 nmol/mg protein and non-heme iron at a concentration of 15 nmol/mg protein. 2) Difference spectra at room temperature and at 70 degrees K show that the preparation is free from contamination with cytochromes c or aa3. Assays of enzyme activity indicate the absence of any of the other catalytic functions normally associated with the mitochondrial respiratory chain. 3) On dissociation and separation on sodium dodecylsulfate-polyacrylamide gels the complex gives rise to seven bands corresponding to subunit polypeptide molecular weights of 43 000, 40 000, 32 000, 24 000, 22 000, 20 000 and 18 000. These appear in a regular stoichiometry of 1:1:3:1:1:1:1.", "contents": "Structure of a cytochrome b-c 1 complex from Saccharomyces cerevisiae YF. 1) An isolation and purification procedure is reported for an active cytochrome b-c1 complex from Saccharomyces cerevisiae. The complex acts as an antimycin A-sensitive duroquinone-cytochrome c reductase and contains cytochromes b and c1 at a concentration of 8 nmol/mg protein and non-heme iron at a concentration of 15 nmol/mg protein. 2) Difference spectra at room temperature and at 70 degrees K show that the preparation is free from contamination with cytochromes c or aa3. Assays of enzyme activity indicate the absence of any of the other catalytic functions normally associated with the mitochondrial respiratory chain. 3) On dissociation and separation on sodium dodecylsulfate-polyacrylamide gels the complex gives rise to seven bands corresponding to subunit polypeptide molecular weights of 43 000, 40 000, 32 000, 24 000, 22 000, 20 000 and 18 000. These appear in a regular stoichiometry of 1:1:3:1:1:1:1."}
{"id": "PMID:200549", "title": "Electron microscopy of a feminizing Leydig cell tumor of the testis.", "content": "The ultrastructural characteristics of a feminizing interstitial (Leydig) cell tumor of the testis were compared with those of normal Leydig cells and with the findings described in 10 published cases of Leydig cell tumor. The neoplastic Leydig cells superficially resembled normal Leydig cells. Similarities included abundant smooth endoplasmic reticulum, lipid, and microbodies. Contrastingly, Reinke crystalloids and paracrystalline inclusions were absent and lipochrome pigment and lysosomes very rare. The nuclei were large and contained enlarged, often multiple, nucleoli. The nuclear membranes tended to be irregular and undulating. Cytoplasmic membranous whorls and myelin figures were conspicuous. Fairly homogeneous fibrous septa were evident between single and grouped tumor cells. Despite several individual variations, there is a general resemblance between the neoplastic Leydig cells in this patient and those previously reported. No distinguishing ultrastructural characteristics were discerned between feminizing and virilizing Leydig cell tumors.", "contents": "Electron microscopy of a feminizing Leydig cell tumor of the testis. The ultrastructural characteristics of a feminizing interstitial (Leydig) cell tumor of the testis were compared with those of normal Leydig cells and with the findings described in 10 published cases of Leydig cell tumor. The neoplastic Leydig cells superficially resembled normal Leydig cells. Similarities included abundant smooth endoplasmic reticulum, lipid, and microbodies. Contrastingly, Reinke crystalloids and paracrystalline inclusions were absent and lipochrome pigment and lysosomes very rare. The nuclei were large and contained enlarged, often multiple, nucleoli. The nuclear membranes tended to be irregular and undulating. Cytoplasmic membranous whorls and myelin figures were conspicuous. Fairly homogeneous fibrous septa were evident between single and grouped tumor cells. Despite several individual variations, there is a general resemblance between the neoplastic Leydig cells in this patient and those previously reported. No distinguishing ultrastructural characteristics were discerned between feminizing and virilizing Leydig cell tumors."}
{"id": "PMID:200550", "title": "Malignant mixed tumor of the parotid gland presenting as a scalp nodule: a case report.", "content": "Malignant mixed tumors of the parotid gland are rare. Metastasizing lesions are even more rare. To the best of our knowledge, this is the first case reported in the English literature in which the scalp nodule was the primary manifestation of the malignant nature of the parotid tumor.", "contents": "Malignant mixed tumor of the parotid gland presenting as a scalp nodule: a case report. Malignant mixed tumors of the parotid gland are rare. Metastasizing lesions are even more rare. To the best of our knowledge, this is the first case reported in the English literature in which the scalp nodule was the primary manifestation of the malignant nature of the parotid tumor."}
{"id": "PMID:200559", "title": "Interaction between cyclic nucleotides and herpes simplex viruses: productive infection.", "content": "Infection of human fibroblasts and HEp-2 cells with herpes simplex virus type 1 (HSV-1) produced a decrease in the intracellular levels of cyclic adenosine 5'- monophosphate (cAMP) and a concomitant increase in the cyclic guanosine 5'- monophosphate (cGMP) levels. In both cell cultures, changes in cyclic nucleotide levels were first observed at 6 h after viral inoculation and were maximal at 12 h. In human fibroblasts, the addition of theophylline, dibutyryl cAMP, or papaverine (cAMP-enhancing compounds) decreased significantly the yield of HSV-1, whereas the addition of insulin or dibutyryl cGMP (cGMP-enhancing compounds) increased the viral yield. In HEp-2 cells, only theophylline decreased the yield of HSV-1, and the cGMP-enhancing compounds had no apparent effect. Cyclic nucleotide enhancing compounds exhibited their effect only if added to either cell culture within the first 3 h after inoculation with HSV-1.", "contents": "Interaction between cyclic nucleotides and herpes simplex viruses: productive infection. Infection of human fibroblasts and HEp-2 cells with herpes simplex virus type 1 (HSV-1) produced a decrease in the intracellular levels of cyclic adenosine 5'- monophosphate (cAMP) and a concomitant increase in the cyclic guanosine 5'- monophosphate (cGMP) levels. In both cell cultures, changes in cyclic nucleotide levels were first observed at 6 h after viral inoculation and were maximal at 12 h. In human fibroblasts, the addition of theophylline, dibutyryl cAMP, or papaverine (cAMP-enhancing compounds) decreased significantly the yield of HSV-1, whereas the addition of insulin or dibutyryl cGMP (cGMP-enhancing compounds) increased the viral yield. In HEp-2 cells, only theophylline decreased the yield of HSV-1, and the cGMP-enhancing compounds had no apparent effect. Cyclic nucleotide enhancing compounds exhibited their effect only if added to either cell culture within the first 3 h after inoculation with HSV-1."}
{"id": "PMID:200560", "title": "New test for endotoxin potency based upon histamine sensitization in mice.", "content": "The results of a test of endotoxic potency based upon the development of histamine hypersensitivity in mice were compared with the results obtained by testing the same materials for pyrogenicity in rabbits and lethality for chicken embryos (CELD50). The results of the histamine hypersensitization test (HHT) correlated well with those of the other two tests. The sensitivity of the HHT was about the same as that of the CELD50 assay. The HHT may provide a relatively inexpensive, fast, and reliable assay method for endotoxin laboratories that do not have the facilities for the more elaborate assays.", "contents": "New test for endotoxin potency based upon histamine sensitization in mice. The results of a test of endotoxic potency based upon the development of histamine hypersensitivity in mice were compared with the results obtained by testing the same materials for pyrogenicity in rabbits and lethality for chicken embryos (CELD50). The results of the histamine hypersensitization test (HHT) correlated well with those of the other two tests. The sensitivity of the HHT was about the same as that of the CELD50 assay. The HHT may provide a relatively inexpensive, fast, and reliable assay method for endotoxin laboratories that do not have the facilities for the more elaborate assays."}
{"id": "PMID:200561", "title": "Immunological and chemical characterization of the extracellular antigens from Corynebacterium vaginale.", "content": "Supernatants from 72-h peptone-starch-dextrose broth cultures of Corynebacterium vaginale contained significant quantities of three extracellular, soluble antigens (ESA). The ESA were concentrated and partially purified by dialysis followed by ammonium sulfate and ethanol precipitation. Diethylaminoethylcellulose columns were used to isolate two of the three ESA. The ESA were shown to be similar to antigens found on whole C. vaginale cells. Absorption studies indicated that the cell antigens are located at, or near, the surface. On the bases of heat stability, resistance to protease treatment, concanavalin A binding activity, and susceptibility to periodate, it appears that all three ESA are polysaccharide or glycoprotein in nature.", "contents": "Immunological and chemical characterization of the extracellular antigens from Corynebacterium vaginale. Supernatants from 72-h peptone-starch-dextrose broth cultures of Corynebacterium vaginale contained significant quantities of three extracellular, soluble antigens (ESA). The ESA were concentrated and partially purified by dialysis followed by ammonium sulfate and ethanol precipitation. Diethylaminoethylcellulose columns were used to isolate two of the three ESA. The ESA were shown to be similar to antigens found on whole C. vaginale cells. Absorption studies indicated that the cell antigens are located at, or near, the surface. On the bases of heat stability, resistance to protease treatment, concanavalin A binding activity, and susceptibility to periodate, it appears that all three ESA are polysaccharide or glycoprotein in nature."}
{"id": "PMID:200562", "title": "Effect of interferon, elevated temperature, and cell type on replication of acute hemorrhagic conjunctivitis viruses.", "content": "Five strains of enterovirus type 70 (E 70) and four of coxsackievirus type A 24 (CA 24) were studied for their sensitivity to interferon (IF), ability to induce IF, replication at various temperatures, and adaptability to human and mouse cell cultures. We found that isolates ranged from 0.01 to 16 times as sensitive to fibroblast IF as vesicular stomatitis virus, depending upon the cell type used and the multiplicity of infection. Most of the isolates induced no detectable IF; however, when induction occurred the titers were relatively low (5 to 300 U). Only E 70 virus isolates were adaptable to growth in L-cells. Replication of all viruses was inhibited approximately 90% at 37 to 39 degrees C depending upon the cell type. These results and the accessibility of the eye to application of IF and/or heat suggests the possibility of their use for treatment. The adaptation of certain E 70 viruses to mouse L-cells opens the possibility of development of a mouse model infection.", "contents": "Effect of interferon, elevated temperature, and cell type on replication of acute hemorrhagic conjunctivitis viruses. Five strains of enterovirus type 70 (E 70) and four of coxsackievirus type A 24 (CA 24) were studied for their sensitivity to interferon (IF), ability to induce IF, replication at various temperatures, and adaptability to human and mouse cell cultures. We found that isolates ranged from 0.01 to 16 times as sensitive to fibroblast IF as vesicular stomatitis virus, depending upon the cell type used and the multiplicity of infection. Most of the isolates induced no detectable IF; however, when induction occurred the titers were relatively low (5 to 300 U). Only E 70 virus isolates were adaptable to growth in L-cells. Replication of all viruses was inhibited approximately 90% at 37 to 39 degrees C depending upon the cell type. These results and the accessibility of the eye to application of IF and/or heat suggests the possibility of their use for treatment. The adaptation of certain E 70 viruses to mouse L-cells opens the possibility of development of a mouse model infection."}
{"id": "PMID:200563", "title": "Mitogenic response of mouse spleen cells and gelation of limulus lysate by lipopolysaccharide of Yersinia pestis and evidence for neutralization of lipopolysaccharide by polymyxin B.", "content": "Lipopolysaccharide (LPS) extracted with phenol and water from Yersinia pestis was compared with LPS of Escherichia coli for stimulation of deoxyribonucleic acid synthesis in mouse spleen cells (lymphocyte mitogenesis), gelation of limulus lysate, pyrogenicity in the rabbit, and susceptibility to inhibition of these activities by polymyxin B sulfate (PBS). LPS of Y. pestis stimulated deoxyribonucleic acid synthesis in mouse spleen cell cultures over the same quantitative range as LPS of E. coli. In the limulus tests and rabbit pyrogenicity studies, the LPS of Y. pestis was active but about 10 times less potent than E. coli LPS on a weight basis. PBS in concentrations from 1 to 10 microgram/ml diminished the rate of deoxyribonucleic acid synthesis in spleen cell cultures stimulated by LPS of both Y. pestis and E. coli. Addition of PBS to LPS of both Y. pestis and E. coli in a ratio of 100 parts of PBS to 1 part of LPS by weight increased by 10-fold the concentration of LPS required to produce gelation of limulus lysate and inhibited significantly pyrogenic responses in rabbits. These results demonstrating similarities of LPS of Y. pestis and E. coli may suggest that the pathogenesis of plague is similar to that of other gram-negative bacterial infections.", "contents": "Mitogenic response of mouse spleen cells and gelation of limulus lysate by lipopolysaccharide of Yersinia pestis and evidence for neutralization of lipopolysaccharide by polymyxin B. Lipopolysaccharide (LPS) extracted with phenol and water from Yersinia pestis was compared with LPS of Escherichia coli for stimulation of deoxyribonucleic acid synthesis in mouse spleen cells (lymphocyte mitogenesis), gelation of limulus lysate, pyrogenicity in the rabbit, and susceptibility to inhibition of these activities by polymyxin B sulfate (PBS). LPS of Y. pestis stimulated deoxyribonucleic acid synthesis in mouse spleen cell cultures over the same quantitative range as LPS of E. coli. In the limulus tests and rabbit pyrogenicity studies, the LPS of Y. pestis was active but about 10 times less potent than E. coli LPS on a weight basis. PBS in concentrations from 1 to 10 microgram/ml diminished the rate of deoxyribonucleic acid synthesis in spleen cell cultures stimulated by LPS of both Y. pestis and E. coli. Addition of PBS to LPS of both Y. pestis and E. coli in a ratio of 100 parts of PBS to 1 part of LPS by weight increased by 10-fold the concentration of LPS required to produce gelation of limulus lysate and inhibited significantly pyrogenic responses in rabbits. These results demonstrating similarities of LPS of Y. pestis and E. coli may suggest that the pathogenesis of plague is similar to that of other gram-negative bacterial infections."}
{"id": "PMID:200564", "title": "Experimental infection of human leukocytes with parainfluenza 1 (6/94) virus.", "content": "Parainfluenza 1 (6/94) virus replicated in both unstimulated and phytohemagglutinin (PHA)-stimulated human peripheral blood leukocytes (PBL). After exposure of PBL to 6/94 virus at a multiplicity of infection of 1, the presence of viral antigen was demonstrated by immunofluorescence in the cytoplasm of less than 1% of unstimulated PBL and 1 to 5% of macrophages. Small amounts (less than 50 mean egg infective doses per ml in most instances) of cell-free virus were present in 18 of 30 (60%) cell cultures tested from 3 to 8 days postinfection. Cell-free virus peaked 6 days postinfection. Virus replication was enhanced in PHA-stimulated cells. Approximately 1 to 10% of PHA-stimulated PBL contained viral antigen as evidenced by immunofluorescence, and cell-free virus was present in 19 of 25 (76%) of the cell cultures tested from 3 to 8 days postinfection. Paramyxovirus nucleocapsids and tubular aggregates were seen in the cytoplasm of approximately 5% of PHA-stimulated PBL and were visualized only in lymphocytes. No other unusual intracytoplasmic or intranuclear structures were seen.", "contents": "Experimental infection of human leukocytes with parainfluenza 1 (6/94) virus. Parainfluenza 1 (6/94) virus replicated in both unstimulated and phytohemagglutinin (PHA)-stimulated human peripheral blood leukocytes (PBL). After exposure of PBL to 6/94 virus at a multiplicity of infection of 1, the presence of viral antigen was demonstrated by immunofluorescence in the cytoplasm of less than 1% of unstimulated PBL and 1 to 5% of macrophages. Small amounts (less than 50 mean egg infective doses per ml in most instances) of cell-free virus were present in 18 of 30 (60%) cell cultures tested from 3 to 8 days postinfection. Cell-free virus peaked 6 days postinfection. Virus replication was enhanced in PHA-stimulated cells. Approximately 1 to 10% of PHA-stimulated PBL contained viral antigen as evidenced by immunofluorescence, and cell-free virus was present in 19 of 25 (76%) of the cell cultures tested from 3 to 8 days postinfection. Paramyxovirus nucleocapsids and tubular aggregates were seen in the cytoplasm of approximately 5% of PHA-stimulated PBL and were visualized only in lymphocytes. No other unusual intracytoplasmic or intranuclear structures were seen."}
{"id": "PMID:200565", "title": "Detection of hepatitis A antigen by immunofluorescence.", "content": "Hepatitis A antigen (HA Ag) was demonstrated by immunofluorescence (IF) in liver biopsies from chimpanzees with experimental hepatitis A virus infection. Blocking experiments with paired sera from patients with hepatitis types A, B, or non-A, non-B, as well as with purified HA Ag, showed that the fluorescence was specific for HA Ag. HA Ag could be demonstrated only in biopsies from chimpanzees inoculated with hepatitis A virus. In two of four chimpanzees biopsied weekly, HA Ag could be detected by IF before stool shedding of HA Ag, elevation in serum alanine aminotransferase (SGPT), or histopathological evidence of liver disease was seen. The HA Ag was detected for 4 to 5 weeks; the last IF-positive biopsy was obtained after SGPT activity had returned to normal. In the two other chimpanzees, HA Ag could be detected only in the biopsy taken at the time of SGPT elevation. In the early IF-positive biopsies, HA Ag was diffusely distributed in the cytoplasm of many cells, but it later accumulated in a focal distribution in the cytoplasm of a few of the hepatocytes and Kupffer cells. This cytoplasmic distribution agrees with previous electron microscopic data.", "contents": "Detection of hepatitis A antigen by immunofluorescence. Hepatitis A antigen (HA Ag) was demonstrated by immunofluorescence (IF) in liver biopsies from chimpanzees with experimental hepatitis A virus infection. Blocking experiments with paired sera from patients with hepatitis types A, B, or non-A, non-B, as well as with purified HA Ag, showed that the fluorescence was specific for HA Ag. HA Ag could be demonstrated only in biopsies from chimpanzees inoculated with hepatitis A virus. In two of four chimpanzees biopsied weekly, HA Ag could be detected by IF before stool shedding of HA Ag, elevation in serum alanine aminotransferase (SGPT), or histopathological evidence of liver disease was seen. The HA Ag was detected for 4 to 5 weeks; the last IF-positive biopsy was obtained after SGPT activity had returned to normal. In the two other chimpanzees, HA Ag could be detected only in the biopsy taken at the time of SGPT elevation. In the early IF-positive biopsies, HA Ag was diffusely distributed in the cytoplasm of many cells, but it later accumulated in a focal distribution in the cytoplasm of a few of the hepatocytes and Kupffer cells. This cytoplasmic distribution agrees with previous electron microscopic data."}
{"id": "PMID:200566", "title": "Physical changes in the epsilon prototoxin molecule of Clostridium perfringens during enzymatic activation.", "content": "Enzymatic activation of Clostridium perfringens epsilon prototoxin removed a small basic part of the molecule, causing a slight change in molecular weight (32,700 to 31,200) and a large change in isoelectric point (from pH 8.02 into fractions of 5.36 and 5.74).", "contents": "Physical changes in the epsilon prototoxin molecule of Clostridium perfringens during enzymatic activation. Enzymatic activation of Clostridium perfringens epsilon prototoxin removed a small basic part of the molecule, causing a slight change in molecular weight (32,700 to 31,200) and a large change in isoelectric point (from pH 8.02 into fractions of 5.36 and 5.74)."}
{"id": "PMID:200567", "title": "Immunological relatedness of papovaviruses of the simian virus 40-polyoma subgroup.", "content": "Viral antigens in permissive cells infected with JC virus, K virus, and SA12 virus were reactive in immunofluorescence tests to antisera against sodium dodecyl sulfate-disrupted simian virus 40 capsids and polyoma VP1. The major capsid polypeptides of all papovaviruses of the simian virus 40-polyoma subgroup are immunologically related.", "contents": "Immunological relatedness of papovaviruses of the simian virus 40-polyoma subgroup. Viral antigens in permissive cells infected with JC virus, K virus, and SA12 virus were reactive in immunofluorescence tests to antisera against sodium dodecyl sulfate-disrupted simian virus 40 capsids and polyoma VP1. The major capsid polypeptides of all papovaviruses of the simian virus 40-polyoma subgroup are immunologically related."}
{"id": "PMID:200568", "title": "Isolation of infectious EB virus from the epithelial tumour cells of nasopharyngeal carcinoma.", "content": "Evidence of herpesvirus replication has been found by light and electron microscopy in the malignant epithelial cells of two out of six nasopharyngeal carcinomas (NPC) examined directly after growth in nude mice to eliminate non-malignant infiltrating cells. The agent has been identified as EB virus by immunofluorescence tests for EB virus capsid antigen, and has been shown to be biologically active by its ability to infect and transform foetal cord blood lymphocytes. Lymphoblastoid cell lines which express the EB virus nuclear antigen have been established from the transformed foetal lymphocytes, and thus carry the first isolate of the virus from the actual epithelial tumour cells of NPC, in a form suitable for further investigation. The results are discussed in terms of the relationship of EB virus to NPC epithelial cells.", "contents": "Isolation of infectious EB virus from the epithelial tumour cells of nasopharyngeal carcinoma. Evidence of herpesvirus replication has been found by light and electron microscopy in the malignant epithelial cells of two out of six nasopharyngeal carcinomas (NPC) examined directly after growth in nude mice to eliminate non-malignant infiltrating cells. The agent has been identified as EB virus by immunofluorescence tests for EB virus capsid antigen, and has been shown to be biologically active by its ability to infect and transform foetal cord blood lymphocytes. Lymphoblastoid cell lines which express the EB virus nuclear antigen have been established from the transformed foetal lymphocytes, and thus carry the first isolate of the virus from the actual epithelial tumour cells of NPC, in a form suitable for further investigation. The results are discussed in terms of the relationship of EB virus to NPC epithelial cells."}
{"id": "PMID:200570", "title": "Complement-dependent cytotoxic antibodies in the course of cervical carcinoma.", "content": "Complement-dependent cytotoxic antibodies to three cervical carcinoma cell lines (Me-180, SW-732 and HeLa) and to Herpes simplex virus type 2 (HSV-2)-infected cells were determined in a long-term study of women with cervical carcinoma. Cytolysis of surface antigens differed significantly between the cervical carcinoma cell lines and HSV-2. Regression of the tumor during treatment was accompanied by decreasing cytolysis in the cervical carcinoma lines, while tumor bearers and patients who became severely ill had high or increasing cytotoxic antibodies, The opposite was noted for the antibody response to HSV-2 infected cells: patients with less advanced cancer had significantly higher cytolytic activity than those who were severely ill or had advanced cancer; long-term survivors demonstrated high, stable lysis of HSV-2 infected cells. As a control of the cervical carcinoma cell lines, cytolytic activity was tested also on a lung carcinoma cell line, A-549. No significant differences were found between the patients with cervical cancer and the control women. Tumor bearers and patients treated for advanced cervical cancer showed a slight but non-significant increase in cytolytic activity on the A-549 line.", "contents": "Complement-dependent cytotoxic antibodies in the course of cervical carcinoma. Complement-dependent cytotoxic antibodies to three cervical carcinoma cell lines (Me-180, SW-732 and HeLa) and to Herpes simplex virus type 2 (HSV-2)-infected cells were determined in a long-term study of women with cervical carcinoma. Cytolysis of surface antigens differed significantly between the cervical carcinoma cell lines and HSV-2. Regression of the tumor during treatment was accompanied by decreasing cytolysis in the cervical carcinoma lines, while tumor bearers and patients who became severely ill had high or increasing cytotoxic antibodies, The opposite was noted for the antibody response to HSV-2 infected cells: patients with less advanced cancer had significantly higher cytolytic activity than those who were severely ill or had advanced cancer; long-term survivors demonstrated high, stable lysis of HSV-2 infected cells. As a control of the cervical carcinoma cell lines, cytolytic activity was tested also on a lung carcinoma cell line, A-549. No significant differences were found between the patients with cervical cancer and the control women. Tumor bearers and patients treated for advanced cervical cancer showed a slight but non-significant increase in cytolytic activity on the A-549 line."}
{"id": "PMID:200572", "title": "Lymphocyte subpopulations and mitogenic responses in nasopharyngeal carcinoma, prior to and after radiotherapy.", "content": "Eighteen patients with nasopharyngeal carcinoma (NPC) were compared to matched controls, before or after cobalt therapy, for the ability of their peripheral blood lymphocytes to: (1) form E and EAC rosettes and (2) mount a proliferative response with PHA, Con A and ALG. A slight decrease in the percentage of E rosettes and a moderate hyporesponsiveness to PHA and Con A were observed before treatment. The statistical significance of these alterations was borderline. Within the group of treated patients a much greater depression, including the response to ALG, was found, although a few long-term survivors responded to mitogens as well as the controls. These findings stress the difficulty of interpreting the results of a longitudinal study of cell-mediated immunity, specific or non-specific, in cancer patients. Finally, by comparing the proliferative response to the three mitogens before and after radiotherapy, it is suggested that their differential effect on these responses might be used in man, as it was in mice, to delineate lymphocyte subpopulations.", "contents": "Lymphocyte subpopulations and mitogenic responses in nasopharyngeal carcinoma, prior to and after radiotherapy. Eighteen patients with nasopharyngeal carcinoma (NPC) were compared to matched controls, before or after cobalt therapy, for the ability of their peripheral blood lymphocytes to: (1) form E and EAC rosettes and (2) mount a proliferative response with PHA, Con A and ALG. A slight decrease in the percentage of E rosettes and a moderate hyporesponsiveness to PHA and Con A were observed before treatment. The statistical significance of these alterations was borderline. Within the group of treated patients a much greater depression, including the response to ALG, was found, although a few long-term survivors responded to mitogens as well as the controls. These findings stress the difficulty of interpreting the results of a longitudinal study of cell-mediated immunity, specific or non-specific, in cancer patients. Finally, by comparing the proliferative response to the three mitogens before and after radiotherapy, it is suggested that their differential effect on these responses might be used in man, as it was in mice, to delineate lymphocyte subpopulations."}
{"id": "PMID:200573", "title": "Glycopeptides from epithelial cell mutants: temperature sensitive for the transformation phenotype.", "content": "Fucose-labelled glycopeptides obtained from the cell surfaces of normal and transformed epithelial cells were compared by co-chromatography on Sephadex G-50. The material obtained from epithelial cells transformed in vitro or from hepatoma cells in culture elutes earlier than the fucose-containing glycopeptides obtained from normal rat epithelial cells. A mutant (TS 223) of a transformed epithelial cell that is temperature-sensitive for maintenance of the transformed phenotype, varies in its Sephadex G-50 profile of cell surface glycopeptides when grown at the permissive (36 degrees C) or the non-permissive temperature (40 degrees C). When grown and labelled at 36 degrees C the gel filtration profile of the glycopeptides resembles that of transformed cells. At 40 degrees C there is an enrichment of later eluting glycopeptides. These differences are more striking in confluent-phase cultures than in log-phase culture. The differences are reversible following upward or downward shifts in growth temperature although there appears to be a lag of at least 6 h before the alteration can be demonstrated by these procedures.", "contents": "Glycopeptides from epithelial cell mutants: temperature sensitive for the transformation phenotype. Fucose-labelled glycopeptides obtained from the cell surfaces of normal and transformed epithelial cells were compared by co-chromatography on Sephadex G-50. The material obtained from epithelial cells transformed in vitro or from hepatoma cells in culture elutes earlier than the fucose-containing glycopeptides obtained from normal rat epithelial cells. A mutant (TS 223) of a transformed epithelial cell that is temperature-sensitive for maintenance of the transformed phenotype, varies in its Sephadex G-50 profile of cell surface glycopeptides when grown at the permissive (36 degrees C) or the non-permissive temperature (40 degrees C). When grown and labelled at 36 degrees C the gel filtration profile of the glycopeptides resembles that of transformed cells. At 40 degrees C there is an enrichment of later eluting glycopeptides. These differences are more striking in confluent-phase cultures than in log-phase culture. The differences are reversible following upward or downward shifts in growth temperature although there appears to be a lag of at least 6 h before the alteration can be demonstrated by these procedures."}
{"id": "PMID:200574", "title": "Virus expression in different tissues of normal and tumor-bearing mice inoculated with a murine leukemia virus.", "content": "Evolution of virus expression in different lymphoid organs as well as in solid syngeneic tumors of mice inoculated with an MuLV was studied with the aid of in vitro XC co-culture technique. When normal adult mice of strain XLII were inoculated intraperitoneally with a cultured Rauscher virus (RC), the virus could be detected, 10 days after inoculation, only in bone marrow in small amounts and thereafter no virus could be found in any of the organs tested, including bone marrow, spleen, thymus, lymph node and kidney. However, when age- and sex-matched parallel mice bearing syngeneic subcutaneous non-viral tumors were inoculated similarly with the RC virus, the virus could be detected abundantly not only in bone marrow and spleen but also in tumors during the first 3 weeks and even 6 weeks after virus inoculation. Transitional decrease or disappearance of the virus was observed around the 25th-31st day in organs and tumors of the inoculated mice. When the tumor mass was removed from these mice by surgery, the virus disappeared rapidly and definitely from all the organs tested. The virus recovered from in vitro explanted and cultured tumors, taken from mice inoculated with the virus, induced typical lymphoid leukemia in BALB/c mice inoculated as newborns. However, from certain aspects (hypertrophy of the thymus and lymph nodes), this virus was different from the original RC virus.", "contents": "Virus expression in different tissues of normal and tumor-bearing mice inoculated with a murine leukemia virus. Evolution of virus expression in different lymphoid organs as well as in solid syngeneic tumors of mice inoculated with an MuLV was studied with the aid of in vitro XC co-culture technique. When normal adult mice of strain XLII were inoculated intraperitoneally with a cultured Rauscher virus (RC), the virus could be detected, 10 days after inoculation, only in bone marrow in small amounts and thereafter no virus could be found in any of the organs tested, including bone marrow, spleen, thymus, lymph node and kidney. However, when age- and sex-matched parallel mice bearing syngeneic subcutaneous non-viral tumors were inoculated similarly with the RC virus, the virus could be detected abundantly not only in bone marrow and spleen but also in tumors during the first 3 weeks and even 6 weeks after virus inoculation. Transitional decrease or disappearance of the virus was observed around the 25th-31st day in organs and tumors of the inoculated mice. When the tumor mass was removed from these mice by surgery, the virus disappeared rapidly and definitely from all the organs tested. The virus recovered from in vitro explanted and cultured tumors, taken from mice inoculated with the virus, induced typical lymphoid leukemia in BALB/c mice inoculated as newborns. However, from certain aspects (hypertrophy of the thymus and lymph nodes), this virus was different from the original RC virus."}
{"id": "PMID:200575", "title": "Immunologic identification of fetal calf serum-derived proteins on the surfaces of cultured transformed and untransformed rat cells.", "content": "The antigens of rat embryo fibroblasts (REF) and of rat Rous sarcoma cells (derived by in vivo passage of oncogenically transformed REF) were studied using the technique of non-ionic detergent solubilization of radiolabelled cells. Solubilized antigens were complexed with rat immune IgG, and precipitation of the complexes was accomplished with rabbit anti-rat IgG. The precipitated radiolabelled antigens were then dissolved in sodium dodecyl sulfate and separated by polyacrylamide gel electrophoresis. This investigation disclosed the existence of cell surface antigenic proteins which are derived from the fetal calf serum (FCS) used in the cell-culture medium. These FCS-dependent antigens include at least three molecular species of approximate molecular weights 95,000, 80,000 and 98,000 daltons. They are probably derived from simple adsorption of FCS proteins to the cell surface, although more complex interactions are possible. One of these proteins (95,000 daltons) is of particular interest. It tenaciously adheres to the cell surface so that a trace amount remains even after subculture in the absence of FCS. Rat Rous sarcomas which are morphologically highly transformed appear to bind very little or none of this protein to their surfaces, whereas untransformed rat embryo fibroblasts bind large quantities. A rat Rous sarcoma line which is intermediate in morphological transformation binds an intermediate amount of this antigen. These findings invite speculation that the interaction of certain serum components with the cell surface may be related to plasma membrane properties which distinguish untransformed and transformed cells.", "contents": "Immunologic identification of fetal calf serum-derived proteins on the surfaces of cultured transformed and untransformed rat cells. The antigens of rat embryo fibroblasts (REF) and of rat Rous sarcoma cells (derived by in vivo passage of oncogenically transformed REF) were studied using the technique of non-ionic detergent solubilization of radiolabelled cells. Solubilized antigens were complexed with rat immune IgG, and precipitation of the complexes was accomplished with rabbit anti-rat IgG. The precipitated radiolabelled antigens were then dissolved in sodium dodecyl sulfate and separated by polyacrylamide gel electrophoresis. This investigation disclosed the existence of cell surface antigenic proteins which are derived from the fetal calf serum (FCS) used in the cell-culture medium. These FCS-dependent antigens include at least three molecular species of approximate molecular weights 95,000, 80,000 and 98,000 daltons. They are probably derived from simple adsorption of FCS proteins to the cell surface, although more complex interactions are possible. One of these proteins (95,000 daltons) is of particular interest. It tenaciously adheres to the cell surface so that a trace amount remains even after subculture in the absence of FCS. Rat Rous sarcomas which are morphologically highly transformed appear to bind very little or none of this protein to their surfaces, whereas untransformed rat embryo fibroblasts bind large quantities. A rat Rous sarcoma line which is intermediate in morphological transformation binds an intermediate amount of this antigen. These findings invite speculation that the interaction of certain serum components with the cell surface may be related to plasma membrane properties which distinguish untransformed and transformed cells."}
{"id": "PMID:200576", "title": "Induction of tumor resistance with BCG-associated tumor antigen.", "content": "Soluble material enriched in tumor-associated antigen was prepared by affinity chromatography from a KCl extract of the chemically-induced D-23 rat hepatoma. Microgram quantities of the above material bound spontaneously to living BCG when the two were incubated briefly in vitro. When injected into normal syngeneic rats, the BCG-associated tumor antigen induced a measure of resistance against challenge with D-23 tumor cells. Peritoneal exudate cells (PEC) obtained from such actively immunized subjects were able to suppress the growth of D-23 tumor cells at a test site in muscle. In contrast, immunization with either BCG alone, tumor protein alone, or tumor protein admixed with BCG in circumstances designed to impede association of the protein, failed to provoke the formation of tumor suppressor PEC. The results encourage of the belief that binding of tumor antigen to BCG favors the induction of a cell-mediated tumor suppressive response.", "contents": "Induction of tumor resistance with BCG-associated tumor antigen. Soluble material enriched in tumor-associated antigen was prepared by affinity chromatography from a KCl extract of the chemically-induced D-23 rat hepatoma. Microgram quantities of the above material bound spontaneously to living BCG when the two were incubated briefly in vitro. When injected into normal syngeneic rats, the BCG-associated tumor antigen induced a measure of resistance against challenge with D-23 tumor cells. Peritoneal exudate cells (PEC) obtained from such actively immunized subjects were able to suppress the growth of D-23 tumor cells at a test site in muscle. In contrast, immunization with either BCG alone, tumor protein alone, or tumor protein admixed with BCG in circumstances designed to impede association of the protein, failed to provoke the formation of tumor suppressor PEC. The results encourage of the belief that binding of tumor antigen to BCG favors the induction of a cell-mediated tumor suppressive response."}
{"id": "PMID:200577", "title": "A review of treatment and rehabilitation legislation regarding alcohol abusers and alcoholics in the United States: 1920-1971.", "content": "A review of various legislative and judicial decisions in the area of alcohol abuse and alcoholism is presented. With heightened awareness of alcoholism as our nation's number one drug problem, the federal government has developed a national institute to coordinate multimodal prevention, treatment, and rehabilitation programs. It is noted that several historical cases promoted the courts and investigating committees to recommend to our states that the crime of public drunkenness be removed. The recently developed Uniform Alcoholism Intoxication Treatment Act is discussed along with some of the intervention techniques being employed to deal with drinking drivers.", "contents": "A review of treatment and rehabilitation legislation regarding alcohol abusers and alcoholics in the United States: 1920-1971. A review of various legislative and judicial decisions in the area of alcohol abuse and alcoholism is presented. With heightened awareness of alcoholism as our nation's number one drug problem, the federal government has developed a national institute to coordinate multimodal prevention, treatment, and rehabilitation programs. It is noted that several historical cases promoted the courts and investigating committees to recommend to our states that the crime of public drunkenness be removed. The recently developed Uniform Alcoholism Intoxication Treatment Act is discussed along with some of the intervention techniques being employed to deal with drinking drivers."}
{"id": "PMID:200581", "title": "The effects of various kinds of sparsely-ionizing radiation on total cell RNA and preribosomal nuclear RNA of Novikoff hepatoma ascites cells after in vivo labelling.", "content": "The effects of 300 kV X-rays, 60Co gamma-rays, 43 MV X-rays and 43 MeV electrons on total cell RNA and 45 S pre-r RNA were investigated in Novikoff Hepatoma ascites cells. Six hours after local irradiation of the animals with 600 rad, the tumour cells were labelled in vivo for 30 and 60 min. The specific activities of high-molecular-weight RNA were influenced differently. This may be due to divergent effects of the applied radiation qualities at the level of transcription and transformation (processing). In addition, these radiation effects are mediated by the adrenal glands in a rather complex manner. Therefore, the results presented in this study support the suggestion that an in vivo labelling system is unsuitable for the evaluation of quantitative radiation effects on RNA.", "contents": "The effects of various kinds of sparsely-ionizing radiation on total cell RNA and preribosomal nuclear RNA of Novikoff hepatoma ascites cells after in vivo labelling. The effects of 300 kV X-rays, 60Co gamma-rays, 43 MV X-rays and 43 MeV electrons on total cell RNA and 45 S pre-r RNA were investigated in Novikoff Hepatoma ascites cells. Six hours after local irradiation of the animals with 600 rad, the tumour cells were labelled in vivo for 30 and 60 min. The specific activities of high-molecular-weight RNA were influenced differently. This may be due to divergent effects of the applied radiation qualities at the level of transcription and transformation (processing). In addition, these radiation effects are mediated by the adrenal glands in a rather complex manner. Therefore, the results presented in this study support the suggestion that an in vivo labelling system is unsuitable for the evaluation of quantitative radiation effects on RNA."}
{"id": "PMID:200582", "title": "A C5'-centred deoxyribose radical in single crystals of 5-chloro-and 5-bromodeoxyuridine X-irradiated at low temperatures.", "content": "X-irradiation at 77 K and subsequent warming to 150 K of single crystals of 5-chloro-and 5-bromodeoxyuridine produces a radical located at position C5' of the deoxyribose moiety. The radical exhibits identical spectral properties in both crystal systems. It is characterized by interaction of the unpaired electron with an alpha-proton(-17-0, -8-7, -33-7G), a beta-proton (18-6, 21-3, 17-5 G) as well as an OH-proton (4-8, 7-9, 12-8 G). The principal values of the g-tensor are 2-0034, 2-0049 and 2-0042. The spectral parameters are discussed in relation to those of the same or similar radicals in other nucleosides (-tides).", "contents": "A C5'-centred deoxyribose radical in single crystals of 5-chloro-and 5-bromodeoxyuridine X-irradiated at low temperatures. X-irradiation at 77 K and subsequent warming to 150 K of single crystals of 5-chloro-and 5-bromodeoxyuridine produces a radical located at position C5' of the deoxyribose moiety. The radical exhibits identical spectral properties in both crystal systems. It is characterized by interaction of the unpaired electron with an alpha-proton(-17-0, -8-7, -33-7G), a beta-proton (18-6, 21-3, 17-5 G) as well as an OH-proton (4-8, 7-9, 12-8 G). The principal values of the g-tensor are 2-0034, 2-0049 and 2-0042. The spectral parameters are discussed in relation to those of the same or similar radicals in other nucleosides (-tides)."}
{"id": "PMID:200584", "title": "In vitro determination of the ability of drugs to bind to adrenergic receptors.", "content": "Alpha- and beta-adrenergic receptors were studied by measuring the binding of 3H-dihydroergocryptine and 3H-dihydroalprenolol, respectively, to membranes prepared from homogenized rabbit iris--ciliary bodies. The binding of 3H-dihydroergocryptine appears to be specific for alpha-adrenergic receptors, since adrenergic agents displace this radioligand with the following order of potency: phentolamine greater than epinephrine greater than or equal to norepinephrine greater than or equal to isoproterenol = propranolol. The binding of 3H-dihydroalprenolol appears to be specific for beta-adrenergic receptors, since adrenergic agents displace this radioligand with the following order of potency: propranolol greater than or equal to isoproterenol greater than or equal to epinephrine greater than norepinephrine greater than or equal to phentolamine. Clonidine and dopamine bind to the alpha-adrenergic receptor but have little activity at the beta-adrenergic receptor. Timolol, d-isoproterenol, and dipivalyl epinephrine bind to the beta-adrenergic receptor but have little activity at the alpha-adrenergic receptor. The results demonstrate that in vitro binding assays for alpha- and beta-adrenergic receptors are useful for studying the mechanism of drug action.", "contents": "In vitro determination of the ability of drugs to bind to adrenergic receptors. Alpha- and beta-adrenergic receptors were studied by measuring the binding of 3H-dihydroergocryptine and 3H-dihydroalprenolol, respectively, to membranes prepared from homogenized rabbit iris--ciliary bodies. The binding of 3H-dihydroergocryptine appears to be specific for alpha-adrenergic receptors, since adrenergic agents displace this radioligand with the following order of potency: phentolamine greater than epinephrine greater than or equal to norepinephrine greater than or equal to isoproterenol = propranolol. The binding of 3H-dihydroalprenolol appears to be specific for beta-adrenergic receptors, since adrenergic agents displace this radioligand with the following order of potency: propranolol greater than or equal to isoproterenol greater than or equal to epinephrine greater than norepinephrine greater than or equal to phentolamine. Clonidine and dopamine bind to the alpha-adrenergic receptor but have little activity at the beta-adrenergic receptor. Timolol, d-isoproterenol, and dipivalyl epinephrine bind to the beta-adrenergic receptor but have little activity at the alpha-adrenergic receptor. The results demonstrate that in vitro binding assays for alpha- and beta-adrenergic receptors are useful for studying the mechanism of drug action."}
{"id": "PMID:200587", "title": "Human cytomegalovirions and dense bodies: glycopeptide analysis and mechanism of cell rounding and polykaryocytosis.", "content": "Human cytomegalovirions and dense bodies labeled with [14C]glucosamine were analyzed by means of sodium dodecyl sulfate-urea polyacrylamide gel electrophoresis and autoradiography. The same glycopeptide composition was found in both cytomegalovirions and dense bodies. These consisted of at least 11 glycopeptides which ranged in molecular weight from 46,500 to over 170,000 daltons. Addition of purified human cytomegalovirus (CMV) at high multiplicity to confluent monolayers of human fibroblasts produced cell rounding and polykaryocytes containing 3 to 150 nuclei. The cell rounding was induced by the cytomegalovirions, but not by the cytomegalo dense bodies. Inhibition of protein synthesis, but not of DNA synthesis, prevented this effect, suggesting that cell rounding is protein mediated. In contrast, the formation of polykaryocytes by CMV was not affected by inhibitors of protein synthesis. UV irradiation of the virus, which abolishes infectivity, does not affect its fusion properties. CMV dense bodies, which contain very little or no DNA, also produce cell fusion although this effect is less pronounced than with virions. CMV-induced polykaryocytosis therefore appears to be a direct result of the interaction of cells with the input viral particles, a phenomenon usually referred to as early polykaryocytosis.", "contents": "Human cytomegalovirions and dense bodies: glycopeptide analysis and mechanism of cell rounding and polykaryocytosis. Human cytomegalovirions and dense bodies labeled with [14C]glucosamine were analyzed by means of sodium dodecyl sulfate-urea polyacrylamide gel electrophoresis and autoradiography. The same glycopeptide composition was found in both cytomegalovirions and dense bodies. These consisted of at least 11 glycopeptides which ranged in molecular weight from 46,500 to over 170,000 daltons. Addition of purified human cytomegalovirus (CMV) at high multiplicity to confluent monolayers of human fibroblasts produced cell rounding and polykaryocytes containing 3 to 150 nuclei. The cell rounding was induced by the cytomegalovirions, but not by the cytomegalo dense bodies. Inhibition of protein synthesis, but not of DNA synthesis, prevented this effect, suggesting that cell rounding is protein mediated. In contrast, the formation of polykaryocytes by CMV was not affected by inhibitors of protein synthesis. UV irradiation of the virus, which abolishes infectivity, does not affect its fusion properties. CMV dense bodies, which contain very little or no DNA, also produce cell fusion although this effect is less pronounced than with virions. CMV-induced polykaryocytosis therefore appears to be a direct result of the interaction of cells with the input viral particles, a phenomenon usually referred to as early polykaryocytosis."}
{"id": "PMID:200590", "title": "Role of the Food and Drug Administration concerning chemical contaminants in animal feeds.", "content": "Chemical contamination of animal feeds and feed ingredients is of concern to the Food and Drug Administration. Contamination by industrial chemicals such as polychlorinated biphenyls and polybrominated biphenyls; heavy metals such as lead, cadmium, and mercury; and pesticides such as dieldrin and chlordane exemplify the problem in feeds and the resulting problem of tissue residues in human foods.", "contents": "Role of the Food and Drug Administration concerning chemical contaminants in animal feeds. Chemical contamination of animal feeds and feed ingredients is of concern to the Food and Drug Administration. Contamination by industrial chemicals such as polychlorinated biphenyls and polybrominated biphenyls; heavy metals such as lead, cadmium, and mercury; and pesticides such as dieldrin and chlordane exemplify the problem in feeds and the resulting problem of tissue residues in human foods."}
{"id": "PMID:200593", "title": "Arrhenoblastoma in a mare.", "content": "An ovarian neoplasm measuring 10 by 8 by 6 cm was surgically removed from a 14-year-old Appaloosa mare. For 2 years prior to surgery, the mare had manifested marked behavioral changes, becoming aggressive toward other broodmares. Histologically, the tumor was found to be an arrhenoblastoma. Preoperative endocrinologic findings (high serum testosterone and low serum estradiol concentrations) supported the diagnosis.", "contents": "Arrhenoblastoma in a mare. An ovarian neoplasm measuring 10 by 8 by 6 cm was surgically removed from a 14-year-old Appaloosa mare. For 2 years prior to surgery, the mare had manifested marked behavioral changes, becoming aggressive toward other broodmares. Histologically, the tumor was found to be an arrhenoblastoma. Preoperative endocrinologic findings (high serum testosterone and low serum estradiol concentrations) supported the diagnosis."}
{"id": "PMID:200594", "title": "Pelvic endometriosis and simian foamy virus infection in a pigtailed macaque.", "content": "Pelvic endometriosis and simian foamy virus infection occurred in a pigtailed macaque. Diffuse omental, peritoneal, and intestinal implantation of endometrium resulted in massive adhesions between adjacent abdominal and pelvic viscera, with formation of a large mass in the right caudal quadrant of the abdomen. Simian foamy virus type 1 was isolated from ectopic endometrium and from the uterine wall but was considered to be merely epiphenomenal.", "contents": "Pelvic endometriosis and simian foamy virus infection in a pigtailed macaque. Pelvic endometriosis and simian foamy virus infection occurred in a pigtailed macaque. Diffuse omental, peritoneal, and intestinal implantation of endometrium resulted in massive adhesions between adjacent abdominal and pelvic viscera, with formation of a large mass in the right caudal quadrant of the abdomen. Simian foamy virus type 1 was isolated from ectopic endometrium and from the uterine wall but was considered to be merely epiphenomenal."}
{"id": "PMID:200596", "title": "Encephalomyocarditis virus infection of captive elephants.", "content": "Four African elephants at each of 2 widely separated zoologic gardens in Florida died following a fulminating illness. Tissue suspensions obtained from an elephant from each of the zoologic gardens were inoculated into newborn mice, 3- to 4-week-old mice, and buffalo green monkey and baby hamster kidney cell cultures. Encephalitis and myocarditis developed in the mice. The cell cultures were destroyed within 24 to 72 hours, and intracytoplasmic viral inclusions were observed in infected cells by electron microscopy. The viral agent was neutralized by known antiserum to encephalomyocarditis virus.", "contents": "Encephalomyocarditis virus infection of captive elephants. Four African elephants at each of 2 widely separated zoologic gardens in Florida died following a fulminating illness. Tissue suspensions obtained from an elephant from each of the zoologic gardens were inoculated into newborn mice, 3- to 4-week-old mice, and buffalo green monkey and baby hamster kidney cell cultures. Encephalitis and myocarditis developed in the mice. The cell cultures were destroyed within 24 to 72 hours, and intracytoplasmic viral inclusions were observed in infected cells by electron microscopy. The viral agent was neutralized by known antiserum to encephalomyocarditis virus."}
{"id": "PMID:200599", "title": "High pressure liquid chromatographic determination of vitamin D3 in livestock feed supplements.", "content": "Vitamin D3 is determined in livestock feed supplements by high pressure liquid chromatography (HPLC). Extracts of the samples are quantitated using normal phase chromatography. If interfering co-extractives are present, an aliquot of the extract is injected on the normal phase column, and the fraction corresponding to vitamin D3 is collected. The vitamin fraction is then further cleaned up and separated from interferences by reverse phase chromatography, and quantitated by measuring the ultraviolet absorption at 254 and 280 nm. The method measures actual vitamin D3 content in the presence of pre-vitamin D, tachysterol, isotachysterol, and vitamin A.", "contents": "High pressure liquid chromatographic determination of vitamin D3 in livestock feed supplements. Vitamin D3 is determined in livestock feed supplements by high pressure liquid chromatography (HPLC). Extracts of the samples are quantitated using normal phase chromatography. If interfering co-extractives are present, an aliquot of the extract is injected on the normal phase column, and the fraction corresponding to vitamin D3 is collected. The vitamin fraction is then further cleaned up and separated from interferences by reverse phase chromatography, and quantitated by measuring the ultraviolet absorption at 254 and 280 nm. The method measures actual vitamin D3 content in the presence of pre-vitamin D, tachysterol, isotachysterol, and vitamin A."}
{"id": "PMID:200600", "title": "Identification of adenosine 3',5'-monophosphate in Mycobacterium smegmatis.", "content": "Cyclic adenosine 3',5'-monophosphate isolated from Mycobacterium smegmatis cells was identified by thin-layer chromatography, stepwise conversion to adenosine 5'-monophosphate and adenosine, ultraviolet absorption spectrum, phosphate analysis, and detection by two relatively specific radioisotopic methods.", "contents": "Identification of adenosine 3',5'-monophosphate in Mycobacterium smegmatis. Cyclic adenosine 3',5'-monophosphate isolated from Mycobacterium smegmatis cells was identified by thin-layer chromatography, stepwise conversion to adenosine 5'-monophosphate and adenosine, ultraviolet absorption spectrum, phosphate analysis, and detection by two relatively specific radioisotopic methods."}
{"id": "PMID:200601", "title": "Outer membranes of gram-negative bacteria. XV. Transmembrane diffusion rates in lipoprotein-deficient mutants of Escherichia coli.", "content": "Permeability of the outer membrane to 6-aminopenicillanic acid was unaltered in an lpo mutant, lacking the Braun lipoprotein, a result suggesting that the lipoproteins by themselves form no or few diffusion pores.", "contents": "Outer membranes of gram-negative bacteria. XV. Transmembrane diffusion rates in lipoprotein-deficient mutants of Escherichia coli. Permeability of the outer membrane to 6-aminopenicillanic acid was unaltered in an lpo mutant, lacking the Braun lipoprotein, a result suggesting that the lipoproteins by themselves form no or few diffusion pores."}
{"id": "PMID:200602", "title": "Direct selective procedure for isolating Neurospora mutants defective in nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase.", "content": "A procedure has been developed for isolating nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (am) mutants of Neurospora. Physiological, genetic, and enzymatic tests show that the new mutants are am alleles. Reconstruction tests and analysis of the new alleles show that the procedure yields a broad spectrum of lesions at the am locus. The isolation of am mutants by this technique appears to be related to the effect of am mutants on the control of the general permease.", "contents": "Direct selective procedure for isolating Neurospora mutants defective in nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase. A procedure has been developed for isolating nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (am) mutants of Neurospora. Physiological, genetic, and enzymatic tests show that the new mutants are am alleles. Reconstruction tests and analysis of the new alleles show that the procedure yields a broad spectrum of lesions at the am locus. The isolation of am mutants by this technique appears to be related to the effect of am mutants on the control of the general permease."}
{"id": "PMID:200603", "title": "Synthesis of ribonucleotides and their participation in ribonucleic acid synthesis by Coxiella burnetii.", "content": "Synthesis of ribonucleic acid (RNA) by the deoxyribonucleic acid-dependent RNA polymerase of Coxiella burnetii required adenosine, uridine, guanosine, and cytidine 5'-triphosphates. Cell-free preparations of this obligate intracellular procaryotic parasite had competence to phosphorylate ribonucleoside mono- and diphosphates in the presence of exogenous adenosine and guanosine 5'-triphosphates to the corresponding di- and triphosphates. C. burnetii contained about 2 nmol of adenosine 5'-triphosphate per mg of protein, which could serve as a approximately P donor for in vivo synthesis of nucleoside triphosphates. The latter were then used as substrates in the synthesis of RNA in a coordinated metabolic system with C. burnetii RNA polymerase. It is suggested that during infection the rickettsiae might obtain the nucleotides necessary for RNA synthesis from the vacuoles in which C. burnetii proliferates.", "contents": "Synthesis of ribonucleotides and their participation in ribonucleic acid synthesis by Coxiella burnetii. Synthesis of ribonucleic acid (RNA) by the deoxyribonucleic acid-dependent RNA polymerase of Coxiella burnetii required adenosine, uridine, guanosine, and cytidine 5'-triphosphates. Cell-free preparations of this obligate intracellular procaryotic parasite had competence to phosphorylate ribonucleoside mono- and diphosphates in the presence of exogenous adenosine and guanosine 5'-triphosphates to the corresponding di- and triphosphates. C. burnetii contained about 2 nmol of adenosine 5'-triphosphate per mg of protein, which could serve as a approximately P donor for in vivo synthesis of nucleoside triphosphates. The latter were then used as substrates in the synthesis of RNA in a coordinated metabolic system with C. burnetii RNA polymerase. It is suggested that during infection the rickettsiae might obtain the nucleotides necessary for RNA synthesis from the vacuoles in which C. burnetii proliferates."}
{"id": "PMID:200604", "title": "Polyadenylate in the virion RNA of mouse hepatitis virus.", "content": "Mouse hepatitis (MH) virus was grown in SR-CDF1-DBT, a mouse cell line, and purified by ammonium sulfate precipitation and by density gradient centrifugation. Extraction of RNA from purified virions with 1% SDS and sedimentation analysis of the RNA revealed a major 50S component and two minor components. Treatment of virions with phenol/chloroform also produced the 50S component, although its yield was lower. MH virion RNA can bind to a poly(U)-fiberglass filter, indicating that MH virion RNA contains poly(A). A poly(A)-like fragment was isolated by digestion with ribonuclease A [EC 3.1.4.22] and T1 [EC 3.1.4.8] and by DEAE-Sephadex column chromatography. Analysis of the fragment for base composition showed it to be an adenine-rich material. Its chain length was about 90 nucleotides, as determined by ion-exchange chromatography and gel electrophoresis.", "contents": "Polyadenylate in the virion RNA of mouse hepatitis virus. Mouse hepatitis (MH) virus was grown in SR-CDF1-DBT, a mouse cell line, and purified by ammonium sulfate precipitation and by density gradient centrifugation. Extraction of RNA from purified virions with 1% SDS and sedimentation analysis of the RNA revealed a major 50S component and two minor components. Treatment of virions with phenol/chloroform also produced the 50S component, although its yield was lower. MH virion RNA can bind to a poly(U)-fiberglass filter, indicating that MH virion RNA contains poly(A). A poly(A)-like fragment was isolated by digestion with ribonuclease A [EC 3.1.4.22] and T1 [EC 3.1.4.8] and by DEAE-Sephadex column chromatography. Analysis of the fragment for base composition showed it to be an adenine-rich material. Its chain length was about 90 nucleotides, as determined by ion-exchange chromatography and gel electrophoresis."}
{"id": "PMID:200606", "title": "Stimulatory effect of histones on phosphorylation of nuclear phosphoproteins.", "content": "Effect of histones on phosphorylation of nuclear phosphoproteins was studied using two species of phosphoprotein kinases with different kinetic and catalytic properties; namely, protein kinases A1 and A2 (Takeda, M., Matsumura, S., & Nakaya, Y. (1974) J. Biochem. 75, 743-751). The reaction rate for protein kinase A1 was markedly enhanced when histone or polylysine was added to the reaction mixture. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the basic protein served as a stimulator rather than acted as a substrate in this reaction. In contrast, when protein kinase A2 was employed, the stimulatory action of these basic proteins was less marked than for protein kinase A1. It seems likely that the phosphorylation of nuclear phosphoproteins, particularly the reaction catalyzed by protein kinase A1, may be strongly influenced by histones which are integrated in the chromatin structure.", "contents": "Stimulatory effect of histones on phosphorylation of nuclear phosphoproteins. Effect of histones on phosphorylation of nuclear phosphoproteins was studied using two species of phosphoprotein kinases with different kinetic and catalytic properties; namely, protein kinases A1 and A2 (Takeda, M., Matsumura, S., & Nakaya, Y. (1974) J. Biochem. 75, 743-751). The reaction rate for protein kinase A1 was markedly enhanced when histone or polylysine was added to the reaction mixture. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the basic protein served as a stimulator rather than acted as a substrate in this reaction. In contrast, when protein kinase A2 was employed, the stimulatory action of these basic proteins was less marked than for protein kinase A1. It seems likely that the phosphorylation of nuclear phosphoproteins, particularly the reaction catalyzed by protein kinase A1, may be strongly influenced by histones which are integrated in the chromatin structure."}
{"id": "PMID:200607", "title": "Essential arginyl residues in yeast phosphoglyceromutase.", "content": "Inactivation of yeast phosphoglyceromutase (tetramer) with 1,2-cyclohexanedione correlates with the modification of six arginyl residues per mole of the enzyme. Protection experiments using 3-phosphoglycerate suggest that four arginyl residues (one residue per subunit) are involved in the binding of the substrate to the enzyme. The modified enzyme reversibly regained its activity upon incubation with hydroxylamine. The reactivity of lysyl residues which have been shown to be involved in the active site is markedly reduced in the enzyme inactivated with 1,2-cyclohexanedione, indicating that the lysyl and arginyl residues are in close proximity in the active site.", "contents": "Essential arginyl residues in yeast phosphoglyceromutase. Inactivation of yeast phosphoglyceromutase (tetramer) with 1,2-cyclohexanedione correlates with the modification of six arginyl residues per mole of the enzyme. Protection experiments using 3-phosphoglycerate suggest that four arginyl residues (one residue per subunit) are involved in the binding of the substrate to the enzyme. The modified enzyme reversibly regained its activity upon incubation with hydroxylamine. The reactivity of lysyl residues which have been shown to be involved in the active site is markedly reduced in the enzyme inactivated with 1,2-cyclohexanedione, indicating that the lysyl and arginyl residues are in close proximity in the active site."}
{"id": "PMID:200608", "title": "Spin-labeling of adenosine triphosphatase in sarcoplasmic reticulum membrane and change in the state of the spin labels induced by deoxycholate.", "content": "Fragmented sarcoplasmic reticulum (SR) was reacted with a thiol-directed spin label, N-(1-oxyl-2,2,6,6,-tetramethyl-4-piperidinyl)maleimide, under various conditions. It was found that ATP inhibited the binding of the label to SR protein in the initial phase of the reaction, but as the incubation time was extended up to 18 h, the amount of label bound to SR protein in the control and ATP-containing samples became almost identical. The Ca2+-dependent ATPase control and ATP-containing samples became almost identical The Ca2+-dependent ATPase (ATP phosphohydrolase [EC 3.6.1.3]) of SR was protected by the presence of ATP during incubation with relatively low concentrations of spin label, irrespective of the total amount of label bound, although with increasing concentration of bound label the ATPase activity decreased. Deoxycholate slightly reduced the rotational freedom of the label bound to SR protein and decreased the initial rate of quenching of protein-bound nitroxide by ascorbate. From an analysis of these results, it was concluded that the binding of deoxycholate to protein decreases the accessibility of ascorbate to the protein-bound label.", "contents": "Spin-labeling of adenosine triphosphatase in sarcoplasmic reticulum membrane and change in the state of the spin labels induced by deoxycholate. Fragmented sarcoplasmic reticulum (SR) was reacted with a thiol-directed spin label, N-(1-oxyl-2,2,6,6,-tetramethyl-4-piperidinyl)maleimide, under various conditions. It was found that ATP inhibited the binding of the label to SR protein in the initial phase of the reaction, but as the incubation time was extended up to 18 h, the amount of label bound to SR protein in the control and ATP-containing samples became almost identical. The Ca2+-dependent ATPase control and ATP-containing samples became almost identical The Ca2+-dependent ATPase (ATP phosphohydrolase [EC 3.6.1.3]) of SR was protected by the presence of ATP during incubation with relatively low concentrations of spin label, irrespective of the total amount of label bound, although with increasing concentration of bound label the ATPase activity decreased. Deoxycholate slightly reduced the rotational freedom of the label bound to SR protein and decreased the initial rate of quenching of protein-bound nitroxide by ascorbate. From an analysis of these results, it was concluded that the binding of deoxycholate to protein decreases the accessibility of ascorbate to the protein-bound label."}
{"id": "PMID:200612", "title": "Thermodynamics of oxidative phosphorylation in bovine heart submitochondrial particles.", "content": "The rates of both forward and reverse electron transfer in phosphorylating submitochondrial particles from bovine heart can be controlled by the thermodynamic phosphorylation potential (deltaGp) of the adenine nucleotide system. deltaGp is the Gibbs free energy of ATP synthesis and is defined by the relationship deltaGp = -deltaG'o + RTln([ATP]/[ADP][Pi]) where deltaG'o is the standard free energy of ATP hydrolysis. Studies of the effects of deltaGp on NADH respiration and the reduction of NAD+ by succinate show that increasing values of deltaGp cause an inhibition of forward electron transfer and a stimulation of reverse electron transfer. Between deltaGp values of 7.6 and 13.0 kcal/mol the rate of NADH respiration decreased 3-fold and the rate of NAD+ reduction by succinate increased 3-fold. Indirect phosphorylation potential titration experiments as well as direct chemical measurements indicate that steady state levels of ATP, ADP, and Pi are established during NADH respiration which correspond to a deltaGp equal to 10.7 to 11.4 kcal/mol.", "contents": "Thermodynamics of oxidative phosphorylation in bovine heart submitochondrial particles. The rates of both forward and reverse electron transfer in phosphorylating submitochondrial particles from bovine heart can be controlled by the thermodynamic phosphorylation potential (deltaGp) of the adenine nucleotide system. deltaGp is the Gibbs free energy of ATP synthesis and is defined by the relationship deltaGp = -deltaG'o + RTln([ATP]/[ADP][Pi]) where deltaG'o is the standard free energy of ATP hydrolysis. Studies of the effects of deltaGp on NADH respiration and the reduction of NAD+ by succinate show that increasing values of deltaGp cause an inhibition of forward electron transfer and a stimulation of reverse electron transfer. Between deltaGp values of 7.6 and 13.0 kcal/mol the rate of NADH respiration decreased 3-fold and the rate of NAD+ reduction by succinate increased 3-fold. Indirect phosphorylation potential titration experiments as well as direct chemical measurements indicate that steady state levels of ATP, ADP, and Pi are established during NADH respiration which correspond to a deltaGp equal to 10.7 to 11.4 kcal/mol."}
{"id": "PMID:200615", "title": "An ultracentrifugal study of the self-association of canine apolipoprotein A-I in solution.", "content": "The sedimentation behavior of canine apolipoprotein (apo) A-I in 0.02 M EDTA, pH 8.6, was studied as a function of protein concentration by the techniques of sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge. At concentrations of less than 1 g/liter, apo-A-I exhibited a monomodal sedimentation pattern, with apparent sedimentation coefficients which varied from 2.3 to 3.5 S with increasing protein concentrations. Above 1.5 g/liter, apo-A-I had two well resolved peaks with s20,w values of 4.15 S and 5.75 S. The proportion of the 5.75 S component increased with increasing apo-A-I concentrations, with a concomitant decrease of the 4.15 S component. By sedimentation equilibrium ultracentrifugation with both the conventional and meniscus-depletion methods, the apparent weight-average molecular weight of apo-A-I was found to be concentration-dependent. At a protein concentration of 5.25 g/liter, an apparent weight average molecular weight of 138,000 was determined, indicating that molecular species larger than a tetramer (monomer molecular weight = 28,000) were present in solution. When analyzed in terms of a reversible self-associating system, the experimental data could best be described according to a monomer-dimer-tetramer-octamer model, as previously reported from human apo-A-I (Vitello, L. B., and Scanu, A. M. (1975) J. Biol. Chem. 251, 1131-1136). The equilibrium constants were: K2 = 4.5 liters/g, K4 = 470 liters3/g3, and K8 = 41,600 liters7/g7, respectively.", "contents": "An ultracentrifugal study of the self-association of canine apolipoprotein A-I in solution. The sedimentation behavior of canine apolipoprotein (apo) A-I in 0.02 M EDTA, pH 8.6, was studied as a function of protein concentration by the techniques of sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge. At concentrations of less than 1 g/liter, apo-A-I exhibited a monomodal sedimentation pattern, with apparent sedimentation coefficients which varied from 2.3 to 3.5 S with increasing protein concentrations. Above 1.5 g/liter, apo-A-I had two well resolved peaks with s20,w values of 4.15 S and 5.75 S. The proportion of the 5.75 S component increased with increasing apo-A-I concentrations, with a concomitant decrease of the 4.15 S component. By sedimentation equilibrium ultracentrifugation with both the conventional and meniscus-depletion methods, the apparent weight-average molecular weight of apo-A-I was found to be concentration-dependent. At a protein concentration of 5.25 g/liter, an apparent weight average molecular weight of 138,000 was determined, indicating that molecular species larger than a tetramer (monomer molecular weight = 28,000) were present in solution. When analyzed in terms of a reversible self-associating system, the experimental data could best be described according to a monomer-dimer-tetramer-octamer model, as previously reported from human apo-A-I (Vitello, L. B., and Scanu, A. M. (1975) J. Biol. Chem. 251, 1131-1136). The equilibrium constants were: K2 = 4.5 liters/g, K4 = 470 liters3/g3, and K8 = 41,600 liters7/g7, respectively."}
{"id": "PMID:200616", "title": "An endonuclease activity of venom phosphodiesterase specific for single-stranded and superhelical DNA.", "content": "A homogeneous preparation of venom phosphodiesterase from Crotalus adamanteus possesses an intrinsic endonuclease activity, specific for superhelical (form I) and single-stranded DNA. The phosphodiesterase degrades single-stranded T7 DNA by endonucleolytic cleavages. Duplex T7 DNA is hydrolyzed by the liberation of acid-soluble products simultaneously from the 3' and 5' termini but without demonstrable internal scissions in duplex regions. Since venom phosphodiesterase is known to hydrolyze oligonucleotides stepwise from the 3' termini, the cleavage at the 5' end of duplex T7 DNA is ascribed to an endonuclease activity. Form I PM2 DNA is nicked to yield first relaxed circles and then linear DNA which is subsequently hydrolyzed only from the chain termini. The linear duplex DNA intermediates consist of a discrete series of fragments (11 are usually resolved on agarose gels) with initial molecular weights ranging from 6.3 x 10(6) (the intact PM2 DNA size) to approximately 1 x 10(6). The cleavage of the form I molecule must, therefore, occur at a limited number of unique sites. The enzyme also cleaves nonsuperhelical, covalently closed circular PM2 DNA but at a 10(4) times slower rate. Both the endonuclease activity on form I DNA and the known exonuclease activity co-migrate on polyacrtkanude gels, are optimally active at pH 9, are stimulated by small concentrations of Mg2+, and are similarly inactivated by heat, reducing agents, and EDTA.", "contents": "An endonuclease activity of venom phosphodiesterase specific for single-stranded and superhelical DNA. A homogeneous preparation of venom phosphodiesterase from Crotalus adamanteus possesses an intrinsic endonuclease activity, specific for superhelical (form I) and single-stranded DNA. The phosphodiesterase degrades single-stranded T7 DNA by endonucleolytic cleavages. Duplex T7 DNA is hydrolyzed by the liberation of acid-soluble products simultaneously from the 3' and 5' termini but without demonstrable internal scissions in duplex regions. Since venom phosphodiesterase is known to hydrolyze oligonucleotides stepwise from the 3' termini, the cleavage at the 5' end of duplex T7 DNA is ascribed to an endonuclease activity. Form I PM2 DNA is nicked to yield first relaxed circles and then linear DNA which is subsequently hydrolyzed only from the chain termini. The linear duplex DNA intermediates consist of a discrete series of fragments (11 are usually resolved on agarose gels) with initial molecular weights ranging from 6.3 x 10(6) (the intact PM2 DNA size) to approximately 1 x 10(6). The cleavage of the form I molecule must, therefore, occur at a limited number of unique sites. The enzyme also cleaves nonsuperhelical, covalently closed circular PM2 DNA but at a 10(4) times slower rate. Both the endonuclease activity on form I DNA and the known exonuclease activity co-migrate on polyacrtkanude gels, are optimally active at pH 9, are stimulated by small concentrations of Mg2+, and are similarly inactivated by heat, reducing agents, and EDTA."}
{"id": "PMID:200617", "title": "Substrate-induced conformational changes in lactate dehydrogenase. Proteolysis of the immobilized enzyme in the presence of specific substrates.", "content": "We report here a new approach to the study of the conformation of enzymes in the presence of specific substrates. Rabbit muscle lactate dehydrogenase was attached to CL-Sepharose via a cleavable spacer arm (-NH-(CH2)6NHCO(CH2)2SS(CH2)2CO-). The bound lactate dehydrogenase was digested with subtilisin BPN' in the presence of substrates of lactate dehydrogenase. The use of a flow system permits the maintenance of saturating levels of substrates. Proteolysis was followed by loss of activity of the enzyme column. The time course of proteolysis in the presence of either NADH, NAD+, or pyruvate alone did not differ from the control. However, when NADH and pyruvate were present simultaneously, the enzyme became more susceptible to proteolysis. The initial rate of proteolysis was increased by 40%. The abortive ternary complex (lactate dehydrogenase - NAD+ - pyruvate) also showed an increase in susceptibility to proteolysis. These findings clearly show that the productive ternary complex (lactate dehydrogenase - NADH - pyruvate) is conformationally different from the apoenzyme and binary complexes under optimal catalytic conditions.", "contents": "Substrate-induced conformational changes in lactate dehydrogenase. Proteolysis of the immobilized enzyme in the presence of specific substrates. We report here a new approach to the study of the conformation of enzymes in the presence of specific substrates. Rabbit muscle lactate dehydrogenase was attached to CL-Sepharose via a cleavable spacer arm (-NH-(CH2)6NHCO(CH2)2SS(CH2)2CO-). The bound lactate dehydrogenase was digested with subtilisin BPN' in the presence of substrates of lactate dehydrogenase. The use of a flow system permits the maintenance of saturating levels of substrates. Proteolysis was followed by loss of activity of the enzyme column. The time course of proteolysis in the presence of either NADH, NAD+, or pyruvate alone did not differ from the control. However, when NADH and pyruvate were present simultaneously, the enzyme became more susceptible to proteolysis. The initial rate of proteolysis was increased by 40%. The abortive ternary complex (lactate dehydrogenase - NAD+ - pyruvate) also showed an increase in susceptibility to proteolysis. These findings clearly show that the productive ternary complex (lactate dehydrogenase - NADH - pyruvate) is conformationally different from the apoenzyme and binary complexes under optimal catalytic conditions."}
{"id": "PMID:200618", "title": "Conformational relaxations of urea- and guanidine hydrochloride-unfolded ferricytochrome c.", "content": "Several recent studies of protein the unfolded proteins. In urea- and guanidine HCl-unfolded ferricytochrome c (horse heart), an acid-induced spin state transformation of the heme group has been detected by the heme absorptions, Trp-59 fluorescence, and the intrinsic viscosity of protein. Kinetics of this second conformational transition, by the temperature jump and stopped flow methods, are complex. One rapid reaction (tau1), pH-independent, occurs in a 50-mus range; the second reaction (tau2), in a 1-ms range, depends linearly upon pH and is faster at the alkaline side; a third reaction (tau3), in a 1-s range, shows a sigmoidal transition at pH 5.1 and is faster at the acidic side. The results are consistent with a kinetic scheme which involves protein conformational changes in the transformation of the heme coordination state. The kinetics, along with previous equilibrium studies, indicate that ligand or charge interactions within a protein molecule are not completely prohibited even in strongly denaturing conditions, such as in high concentrations of urea and guanidine HCl. Thus, local structures of peptide chain associated with these interactions can exist in the unfolded protein.", "contents": "Conformational relaxations of urea- and guanidine hydrochloride-unfolded ferricytochrome c. Several recent studies of protein the unfolded proteins. In urea- and guanidine HCl-unfolded ferricytochrome c (horse heart), an acid-induced spin state transformation of the heme group has been detected by the heme absorptions, Trp-59 fluorescence, and the intrinsic viscosity of protein. Kinetics of this second conformational transition, by the temperature jump and stopped flow methods, are complex. One rapid reaction (tau1), pH-independent, occurs in a 50-mus range; the second reaction (tau2), in a 1-ms range, depends linearly upon pH and is faster at the alkaline side; a third reaction (tau3), in a 1-s range, shows a sigmoidal transition at pH 5.1 and is faster at the acidic side. The results are consistent with a kinetic scheme which involves protein conformational changes in the transformation of the heme coordination state. The kinetics, along with previous equilibrium studies, indicate that ligand or charge interactions within a protein molecule are not completely prohibited even in strongly denaturing conditions, such as in high concentrations of urea and guanidine HCl. Thus, local structures of peptide chain associated with these interactions can exist in the unfolded protein."}
{"id": "PMID:200621", "title": "Failure of cultured chick embryo fibroblasts to incorporate collagen into their extracellular matrix when transformed by Rous sarcoma virus. An effect of transformation but not of virus production.", "content": "Whole chick embryo fibroblasts were infected with the Prague wild type Rous sarcoma virus and with a temperature sensitive mutant of this strain, RSVtsLA24. Normal fibroblasts and fibroblasts infected with the temperature-sensitive mutant and cultured at the nonpermissive temperature-sensitive mutant and cultured at the nonpermissive temperature, secreted procollagen into the medium and incorporated collagen into their extracellular matrix. On the other hand, transformed fibroblasts and fibroblasts infected with the temperature-sensitive mutant and cultured at the permissive temperature, were able to secrete procollagen into the medium, but there was no evidence that they were able to convert procollagen to collagen and incorporate collagen into an extracellular matrix. The inability of the infected cells to incorporate collagen into an extracellular matrix was found to be a result of transformation rather than of virus production in these cells.", "contents": "Failure of cultured chick embryo fibroblasts to incorporate collagen into their extracellular matrix when transformed by Rous sarcoma virus. An effect of transformation but not of virus production. Whole chick embryo fibroblasts were infected with the Prague wild type Rous sarcoma virus and with a temperature sensitive mutant of this strain, RSVtsLA24. Normal fibroblasts and fibroblasts infected with the temperature-sensitive mutant and cultured at the nonpermissive temperature-sensitive mutant and cultured at the nonpermissive temperature, secreted procollagen into the medium and incorporated collagen into their extracellular matrix. On the other hand, transformed fibroblasts and fibroblasts infected with the temperature-sensitive mutant and cultured at the permissive temperature, were able to secrete procollagen into the medium, but there was no evidence that they were able to convert procollagen to collagen and incorporate collagen into an extracellular matrix. The inability of the infected cells to incorporate collagen into an extracellular matrix was found to be a result of transformation rather than of virus production in these cells."}
{"id": "PMID:200626", "title": "Impaired intracellular migration and altered solubility of nonglycosylated glycoproteins of vesicular stomatitis virus and Sindbis virus.", "content": "Tunicamycin, an antibiotic which prevents the glycosylation of newly synthesized proteins, inhibits the replication of both vesicular stomatitis virus and Sindbis virus. In tunicamycin-treated infected cells, all of the viral proteins are synthesized but the glycoproteins are devoid of carbohydrate. The nonglycosylated glycoproteins could not be detected on the outside of the plasma membrane by lactoperoxidase labeling, indirect immunofluorescence staining, or chymotrypsin treatment of intact cells, whereas the glycosylated glycoproteins were readily detected by all three methods. These results indicate that the bulk of the nonglycosylated glycoproteins are unable to undergo the normal migration to the cell surface. In contrast to the normal glycosylated viral glycoproteins, the nonglycosylated glycoproteins were insoluble in nonionic detergents such as Triton X-100. The nonglycosylated glycoprotein of vesicular stomatitis virus could be solubilized using a combination of 6 M guanidine hydrochloride and 0.2% Triton X-100, but precipitated when the 6 M guanidine was removed by dialysis. These results suggest that the lack of carbohydrate alters the properties of the glycoproteins, which may explain their impaired mobility through the intracellular membranous system.", "contents": "Impaired intracellular migration and altered solubility of nonglycosylated glycoproteins of vesicular stomatitis virus and Sindbis virus. Tunicamycin, an antibiotic which prevents the glycosylation of newly synthesized proteins, inhibits the replication of both vesicular stomatitis virus and Sindbis virus. In tunicamycin-treated infected cells, all of the viral proteins are synthesized but the glycoproteins are devoid of carbohydrate. The nonglycosylated glycoproteins could not be detected on the outside of the plasma membrane by lactoperoxidase labeling, indirect immunofluorescence staining, or chymotrypsin treatment of intact cells, whereas the glycosylated glycoproteins were readily detected by all three methods. These results indicate that the bulk of the nonglycosylated glycoproteins are unable to undergo the normal migration to the cell surface. In contrast to the normal glycosylated viral glycoproteins, the nonglycosylated glycoproteins were insoluble in nonionic detergents such as Triton X-100. The nonglycosylated glycoprotein of vesicular stomatitis virus could be solubilized using a combination of 6 M guanidine hydrochloride and 0.2% Triton X-100, but precipitated when the 6 M guanidine was removed by dialysis. These results suggest that the lack of carbohydrate alters the properties of the glycoproteins, which may explain their impaired mobility through the intracellular membranous system."}
{"id": "PMID:200627", "title": "Studies of low molecular weight RNA from cells infected with adenovirus 2. III. The sequence of the promoter for VA-RNA I.", "content": "VA-RNA I is one of the very few RNA species produced in animal cells whose transcriptional initiation site is known precisely. We have analyzed the nucleotide sequence of the DNA preceding the 5' end of VA-RNA I and compared it with known prokaryotic promoters and presumptive eukaryotic promoters.", "contents": "Studies of low molecular weight RNA from cells infected with adenovirus 2. III. The sequence of the promoter for VA-RNA I. VA-RNA I is one of the very few RNA species produced in animal cells whose transcriptional initiation site is known precisely. We have analyzed the nucleotide sequence of the DNA preceding the 5' end of VA-RNA I and compared it with known prokaryotic promoters and presumptive eukaryotic promoters."}
{"id": "PMID:200631", "title": "Mitotic activity of differentiated goldfish erythrophores in culture.", "content": "Integumental erythrophores on the scales of xanthic goldfishes were dissociated and cultured in a monolayer for about 30 days. The proportion of erythrophores in the culture was about 50% at the beginning of cultivation. Erythrophores in culture were characterized by the aggregate of orange-coloured pigment in the centre of the cell body. With the progress of culture the erythrophores develop a few elongated dendritic processes and came to rest on a monolayer sheet of coexisting non-pigmented cells. The erythrophores responded to adrenocorticotropic hormone (ACTH) by producing reversible pigment dispersion and this response was retained throughout the whole period of culture. Dividing erythrophores were found first within 3 days of cultivation and at all times after that. The number  of the erythrophores doubled within 9 days of cultivation and trebled within 16 days. Thus, evidence was provided that differentiated erythrophores of the goldfish still showed mitotic activity in vitro, in contrast to the generally accepted view that fish chromatophores are kind of terminally differentiated cell.", "contents": "Mitotic activity of differentiated goldfish erythrophores in culture. Integumental erythrophores on the scales of xanthic goldfishes were dissociated and cultured in a monolayer for about 30 days. The proportion of erythrophores in the culture was about 50% at the beginning of cultivation. Erythrophores in culture were characterized by the aggregate of orange-coloured pigment in the centre of the cell body. With the progress of culture the erythrophores develop a few elongated dendritic processes and came to rest on a monolayer sheet of coexisting non-pigmented cells. The erythrophores responded to adrenocorticotropic hormone (ACTH) by producing reversible pigment dispersion and this response was retained throughout the whole period of culture. Dividing erythrophores were found first within 3 days of cultivation and at all times after that. The number  of the erythrophores doubled within 9 days of cultivation and trebled within 16 days. Thus, evidence was provided that differentiated erythrophores of the goldfish still showed mitotic activity in vitro, in contrast to the generally accepted view that fish chromatophores are kind of terminally differentiated cell."}
{"id": "PMID:200633", "title": "Adrenocortical function in hyperprolactinemic women.", "content": "To study the effects of prolactin (PRL) on adrenocortical function in humans, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (delta) and testosterone (T) were measured in serum obtained from 35 hyperprolactinemic women with galactorrhea and amenorrhea before and after treatment with bromocriptine-induced fall in mean PRL levels from 82 +/- 8 (SE) to 14 +/- 2 ng/ml (n = 39, P less than 0.0005), DHAS fell from 322 +/- 21 to 237 +/- 21 microgram/dl (n = 39); P less than 0.0005), DHA fell from 492 +/- 47 to 378 +/- 30 ng/dl (n = 39; P less than 0.01) while T (n = 16) and delta (n = 13) levels were unchanges (44 +/- 4 vs. 49 +/- 4 ng/dl and 280 +/- 55 vs. 236 +/- 40 ng/dl, respectively). In addition, 4 women were infused iv with 25 microgram synthetic ACTH over 4 h and serial blood samples drawn while hyperprolactinemic, and again 2-4 months later following normalization of PRL levels by bromocriptine. Although pre-infusion levels of DHAS were lower when PRL levels were normalized, no significant differences in responses of circulating DHAS, DHA, T, cortisol and 17-hydroxyprogesterone concentrations were detected between the two infusions. Since DHAS is virtually an exclusive product of the adrenal cortex, and since high PRL levels appear to inhibit ovarian steroid production, the findings suggest that hyperprolactinemia selectively stimulates adrenocortical androgen production.", "contents": "Adrenocortical function in hyperprolactinemic women. To study the effects of prolactin (PRL) on adrenocortical function in humans, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (delta) and testosterone (T) were measured in serum obtained from 35 hyperprolactinemic women with galactorrhea and amenorrhea before and after treatment with bromocriptine-induced fall in mean PRL levels from 82 +/- 8 (SE) to 14 +/- 2 ng/ml (n = 39, P less than 0.0005), DHAS fell from 322 +/- 21 to 237 +/- 21 microgram/dl (n = 39); P less than 0.0005), DHA fell from 492 +/- 47 to 378 +/- 30 ng/dl (n = 39; P less than 0.01) while T (n = 16) and delta (n = 13) levels were unchanges (44 +/- 4 vs. 49 +/- 4 ng/dl and 280 +/- 55 vs. 236 +/- 40 ng/dl, respectively). In addition, 4 women were infused iv with 25 microgram synthetic ACTH over 4 h and serial blood samples drawn while hyperprolactinemic, and again 2-4 months later following normalization of PRL levels by bromocriptine. Although pre-infusion levels of DHAS were lower when PRL levels were normalized, no significant differences in responses of circulating DHAS, DHA, T, cortisol and 17-hydroxyprogesterone concentrations were detected between the two infusions. Since DHAS is virtually an exclusive product of the adrenal cortex, and since high PRL levels appear to inhibit ovarian steroid production, the findings suggest that hyperprolactinemia selectively stimulates adrenocortical androgen production."}
{"id": "PMID:200634", "title": "Anaerobes in human biliary tracts.", "content": "During a 2-year period, 1,892 patients underwent biliary tract surgery at the Mayo Clinic. Both aerobic and anaerobic cultures of bile were performed in 371 of these patients. Sixty-nine percent of the cultures were positive, and 41% (117) of these grew anaerobes, although they were present in pure culture only twice. Mixed cultures most commonly contained four different organisms (three aerobes and one anaerobe). Bacteroides fragilis was the single most commonly isolated anaerobe and ranked fourth in terms of overall isolates behind Escherichia coli, group D streptococci, and Klebsiella B. fragilis accounted for 7.0% of the total group D streptococci, and Klebsiella. B. fragilis accounted for 7.0% of the total aerobic and anaerobic isolates and was present in 21% of all positive cultures. Pseudomonas aeruginosa and Clostridium perfringens ranked fifth and sixth, providing 6.5 and 5.9% of all isolates, respectively. This study demonstrates the frequent presence of anaerobes in patients with bactibilia and suggests that they be considered in the formulation of antimicrobial therapy for infections involving human biliary tracts.", "contents": "Anaerobes in human biliary tracts. During a 2-year period, 1,892 patients underwent biliary tract surgery at the Mayo Clinic. Both aerobic and anaerobic cultures of bile were performed in 371 of these patients. Sixty-nine percent of the cultures were positive, and 41% (117) of these grew anaerobes, although they were present in pure culture only twice. Mixed cultures most commonly contained four different organisms (three aerobes and one anaerobe). Bacteroides fragilis was the single most commonly isolated anaerobe and ranked fourth in terms of overall isolates behind Escherichia coli, group D streptococci, and Klebsiella B. fragilis accounted for 7.0% of the total group D streptococci, and Klebsiella. B. fragilis accounted for 7.0% of the total aerobic and anaerobic isolates and was present in 21% of all positive cultures. Pseudomonas aeruginosa and Clostridium perfringens ranked fifth and sixth, providing 6.5 and 5.9% of all isolates, respectively. This study demonstrates the frequent presence of anaerobes in patients with bactibilia and suggests that they be considered in the formulation of antimicrobial therapy for infections involving human biliary tracts."}
{"id": "PMID:200635", "title": "Enzyme-linked immunosorbent assay for diagnosis of rotavirus infections in calves.", "content": "An enzyme-linked immunosorbent assay for the diagnosis of rotavirus infection in calves is described. The assay was more efficient for the detection of rotavirus antigens in calf feces than were electron microscopy and immunoelectroosmorphoresis.", "contents": "Enzyme-linked immunosorbent assay for diagnosis of rotavirus infections in calves. An enzyme-linked immunosorbent assay for the diagnosis of rotavirus infection in calves is described. The assay was more efficient for the detection of rotavirus antigens in calf feces than were electron microscopy and immunoelectroosmorphoresis."}
{"id": "PMID:200636", "title": "The development and degeneration of Purkinje cells in pcd mutant mice.", "content": "Purkinje cell degeneration (pcd), an autosomal recessive mutation in the mouse, causes the postnatal death of virtually all cerebellar Purkinje cells during the third and fourth postnatal week. We have compared the postnatal development of normal and pcd mutant Purkinje cells. The early deviations from normal development involve primarily the perikaryonal polysomes and endoplasmic reticulum. Many of the mutant Purkinje cells retain abnormally the basal accumulation of polysomes, a finding which permits the identification of affected animals at postnatal day 15, one week prior to the onset of behavioral abnormalities. In addition, the affected Purkinje cells possess unusual configurations of endoplasmic reticulum with associated electron-dense particles similar to but larger than ribosomes, mature and forming intracisternal A particles and nematosomes. Before the pcd Purkinje cells degenerate they appear to receive all their appropriate synaptic contacts. Some disruption, however, of parallel fiber: Purkinje spine synaptogenesis occurs at late stages of development. Some spines lack presynaptic elements, postsynaptic thickenings are present along the dendritic shafts and parallel fibers appear to make synaptic contacts directly onto the shafts. The spectrum of early morphological changes that has been observed in pcd mutant Purkinje cells is thus far unique to this cerebellar abnormality.", "contents": "The development and degeneration of Purkinje cells in pcd mutant mice. Purkinje cell degeneration (pcd), an autosomal recessive mutation in the mouse, causes the postnatal death of virtually all cerebellar Purkinje cells during the third and fourth postnatal week. We have compared the postnatal development of normal and pcd mutant Purkinje cells. The early deviations from normal development involve primarily the perikaryonal polysomes and endoplasmic reticulum. Many of the mutant Purkinje cells retain abnormally the basal accumulation of polysomes, a finding which permits the identification of affected animals at postnatal day 15, one week prior to the onset of behavioral abnormalities. In addition, the affected Purkinje cells possess unusual configurations of endoplasmic reticulum with associated electron-dense particles similar to but larger than ribosomes, mature and forming intracisternal A particles and nematosomes. Before the pcd Purkinje cells degenerate they appear to receive all their appropriate synaptic contacts. Some disruption, however, of parallel fiber: Purkinje spine synaptogenesis occurs at late stages of development. Some spines lack presynaptic elements, postsynaptic thickenings are present along the dendritic shafts and parallel fibers appear to make synaptic contacts directly onto the shafts. The spectrum of early morphological changes that has been observed in pcd mutant Purkinje cells is thus far unique to this cerebellar abnormality."}
{"id": "PMID:200637", "title": "The effects of formocresol on rat sponge implant tissue: a biochemical study.", "content": "An investigation was conducted on the effect of formocresol treatment of the aqueous extractability and enzymatic susceptibility of excised implant tissue. The treated tissue demonstrated a decreased solubility and a diminished digestibility by trypsin, pepsin and collagenase. However, its reactivity toward hyaluronidase showed little alteration.", "contents": "The effects of formocresol on rat sponge implant tissue: a biochemical study. An investigation was conducted on the effect of formocresol treatment of the aqueous extractability and enzymatic susceptibility of excised implant tissue. The treated tissue demonstrated a decreased solubility and a diminished digestibility by trypsin, pepsin and collagenase. However, its reactivity toward hyaluronidase showed little alteration."}
{"id": "PMID:200638", "title": "A laboratory evaluation of the effect of two surface-wetting treatments on soft denture liners.", "content": "The wettability of acrylic and silicone soft denture-liners was improved by two methods of surface treatment. They consisted of formation of a thin film of silica from the application of silicon tetrachloride, and by cross-linking the surface molecules and bombarding with hydroxyl free radicals. Softness and water sorption were monitored throughout the study.", "contents": "A laboratory evaluation of the effect of two surface-wetting treatments on soft denture liners. The wettability of acrylic and silicone soft denture-liners was improved by two methods of surface treatment. They consisted of formation of a thin film of silica from the application of silicon tetrachloride, and by cross-linking the surface molecules and bombarding with hydroxyl free radicals. Softness and water sorption were monitored throughout the study."}
{"id": "PMID:200672", "title": "Inorganic trimetaphosphatase as a histochemical marker for lysosomes in light and electron microscopy.", "content": "A new cytochemical method is presented for the light and electron microscopic localization of lysosomes in mineralized and soft tissues. Inorganic trimetaphosphate is used as substrate in a lead chelate incubation medium at pH 3.9. Lysosomes in several tissues are strongly reactive, and reaction product is frequently present in Golgi saccules and GERL. The reaction can be differentiated from acid glycerophosphatase activity, is relatively insensitive to fixation and demineralization procedures, and the reaction is often complete after short incubation times.", "contents": "Inorganic trimetaphosphatase as a histochemical marker for lysosomes in light and electron microscopy. A new cytochemical method is presented for the light and electron microscopic localization of lysosomes in mineralized and soft tissues. Inorganic trimetaphosphate is used as substrate in a lead chelate incubation medium at pH 3.9. Lysosomes in several tissues are strongly reactive, and reaction product is frequently present in Golgi saccules and GERL. The reaction can be differentiated from acid glycerophosphatase activity, is relatively insensitive to fixation and demineralization procedures, and the reaction is often complete after short incubation times."}
{"id": "PMID:200673", "title": "Experimental protein malnutrition in primates: electronmicroscopic observations on the cerebellum of healthy and malnourished squirrel monkeys (Saimiri sciureus).", "content": "Eight young adult squirrel monkeys were maintained on a protein deficient (2% calories from proteins) diet for a period of 15 weeks during which the animals lost wieght steadily and developed varying degrees of sensory and motor impairments as evidenced by lack of interest in the surrounding environment and changes in posture and gait. An additional eight animals were maintained on a high protein diet (25% calories from proteins) to serve as controls. Two animals each from the experimental and control groups were sacrificed at 9, 11, 13 and 15 weeks of special feeding schedule. The Purkinje cells of the cerebellum of malnourished animals showed significant changes in the ribosomes, endoplasmic reticulum and Golgi zone indicating greatly disturbed protein metabolism. The granule cells, especially of the pale variety show prominent watery swellings with scant cell organelles. The most prominent change appeared in various types of neurons related to the multiplication of various types of lysosomes, multivesicular lamellar bodies and the lipofuscin pigment bodies. In the animals sacrificed at different intervals, the relatively more malnourished animals showed significantly larger number of lipofuscin pigment in the various types of neurons of the cerebellar cortex. The dendritic changes included honey-comb formation in the lumen. The astrocyte glial fibers were greatly increased. The pericytes of the blood vessels showed irregular outlines and were greatly enlarged with numerous osmiophilic bodies (presumably lipofuscin) in the experimental animals as compared to the controls.", "contents": "Experimental protein malnutrition in primates: electronmicroscopic observations on the cerebellum of healthy and malnourished squirrel monkeys (Saimiri sciureus). Eight young adult squirrel monkeys were maintained on a protein deficient (2% calories from proteins) diet for a period of 15 weeks during which the animals lost wieght steadily and developed varying degrees of sensory and motor impairments as evidenced by lack of interest in the surrounding environment and changes in posture and gait. An additional eight animals were maintained on a high protein diet (25% calories from proteins) to serve as controls. Two animals each from the experimental and control groups were sacrificed at 9, 11, 13 and 15 weeks of special feeding schedule. The Purkinje cells of the cerebellum of malnourished animals showed significant changes in the ribosomes, endoplasmic reticulum and Golgi zone indicating greatly disturbed protein metabolism. The granule cells, especially of the pale variety show prominent watery swellings with scant cell organelles. The most prominent change appeared in various types of neurons related to the multiplication of various types of lysosomes, multivesicular lamellar bodies and the lipofuscin pigment bodies. In the animals sacrificed at different intervals, the relatively more malnourished animals showed significantly larger number of lipofuscin pigment in the various types of neurons of the cerebellar cortex. The dendritic changes included honey-comb formation in the lumen. The astrocyte glial fibers were greatly increased. The pericytes of the blood vessels showed irregular outlines and were greatly enlarged with numerous osmiophilic bodies (presumably lipofuscin) in the experimental animals as compared to the controls."}
{"id": "PMID:200674", "title": "A test for the assessment of disinfectant/sanitizers used for napkin storage.", "content": "A test is described for assessing the effect of hypochlorites in reducing the bacterial load on soiled napkins during storage, between removal from the infant and laundering.", "contents": "A test for the assessment of disinfectant/sanitizers used for napkin storage. A test is described for assessing the effect of hypochlorites in reducing the bacterial load on soiled napkins during storage, between removal from the infant and laundering."}
{"id": "PMID:200675", "title": "Identification of pregnancies at risk from cytomegalovirus infection.", "content": "The fluorescent antibody technique was used for the identification of specific cytomegalovirus IgM in the sera of twenty-four of 1065 unmarried pregnant women. Seventeen of them were followed to term and five infected infants were identified. Two other infants had CMV IgM in neonatal serum samples but virus excretion was not demonstrated. The congenital infection rate in this study was 5.3 per 1000 births by virus excretion and 7.9 per 1000 if cases with specific IgM are included; from previous studies a rate of 8.8 per 1000 was expected. The reasons for the lack of relationship between specific IgM in the mothers' serum and infected babies is discussed.", "contents": "Identification of pregnancies at risk from cytomegalovirus infection. The fluorescent antibody technique was used for the identification of specific cytomegalovirus IgM in the sera of twenty-four of 1065 unmarried pregnant women. Seventeen of them were followed to term and five infected infants were identified. Two other infants had CMV IgM in neonatal serum samples but virus excretion was not demonstrated. The congenital infection rate in this study was 5.3 per 1000 births by virus excretion and 7.9 per 1000 if cases with specific IgM are included; from previous studies a rate of 8.8 per 1000 was expected. The reasons for the lack of relationship between specific IgM in the mothers' serum and infected babies is discussed."}
{"id": "PMID:200676", "title": "Distribution and titres of rotavirus antibodies in different age groups.", "content": "Three hundred and fifty-seven sera selected at random from hospital patients of all ages were examined for rotavirus antibodies using indirect immunofluorescence (FA) and complement fixation levels (CFT). Three hundred and fourteen of these were also tested for neutralizing antibodies to human rotavirus. Sera from patients admitted with a diagnosis of acute gastroenteritis were excluded from this survey. FA antibodies were found in newborn infants but fell to undetectable titres at 3 months. The highest titres were found in children between the ages of one and three years. In older age groups, the model titre fell gradually with increasing age until, in sera from those above 70 years of age, FA antibodies were almost undetectable. The same pattern was observed with neutralizing antibodies. A high model titre of CF antibodies was only found in sera from those aged one to three years.", "contents": "Distribution and titres of rotavirus antibodies in different age groups. Three hundred and fifty-seven sera selected at random from hospital patients of all ages were examined for rotavirus antibodies using indirect immunofluorescence (FA) and complement fixation levels (CFT). Three hundred and fourteen of these were also tested for neutralizing antibodies to human rotavirus. Sera from patients admitted with a diagnosis of acute gastroenteritis were excluded from this survey. FA antibodies were found in newborn infants but fell to undetectable titres at 3 months. The highest titres were found in children between the ages of one and three years. In older age groups, the model titre fell gradually with increasing age until, in sera from those above 70 years of age, FA antibodies were almost undetectable. The same pattern was observed with neutralizing antibodies. A high model titre of CF antibodies was only found in sera from those aged one to three years."}
{"id": "PMID:200677", "title": "The metabolic inhibition test for mycoplasmas based on phosphatase production.", "content": "A metabolic inhibition test based upon phosphatase production is described. This is of value for those Mycoplasma species which produce phosphatase but which cannot be examined by the previously published metabolic inhibition techniques.", "contents": "The metabolic inhibition test for mycoplasmas based on phosphatase production. A metabolic inhibition test based upon phosphatase production is described. This is of value for those Mycoplasma species which produce phosphatase but which cannot be examined by the previously published metabolic inhibition techniques."}
{"id": "PMID:200679", "title": "Scanning electron microscopic study of hamster tracheal organ cultures infected with Bordetella pertussis.", "content": "Hamster tracheal organculture was employed as a model for the study of the pathogenesis of infection due to bordetella pertusis. Scanning electron microscopy provided a three-dimensional view of the surface infection of the tracheal explants. Phase I B. pertussis attached only to the ciliated epithelial cells, and a sequence of events involving the injury, expulsion, and destruction of these differentiated cells occurred. This in vitro model provides insights into the mechanisms by which B. pertussis mediates host cell injury at the site of infection.", "contents": "Scanning electron microscopic study of hamster tracheal organ cultures infected with Bordetella pertussis. Hamster tracheal organculture was employed as a model for the study of the pathogenesis of infection due to bordetella pertusis. Scanning electron microscopy provided a three-dimensional view of the surface infection of the tracheal explants. Phase I B. pertussis attached only to the ciliated epithelial cells, and a sequence of events involving the injury, expulsion, and destruction of these differentiated cells occurred. This in vitro model provides insights into the mechanisms by which B. pertussis mediates host cell injury at the site of infection."}
{"id": "PMID:200680", "title": "Diagnostic skin test reactions with varicella virus antigen and clinical application of the test.", "content": "Varicella virus antigen was prepared and used in skin testing of 75 children one to 17 years old. Results of skin tests were analyzed in relation to history of varicella, presence of absence of neutralizing antibody, and susceptibility to clinical varicella. All 22 children with no history of varicella and no neutralizing antibody were negative in the skin test when an erythematous change of greater than or equal to 5 mm in diameter was taken as a positive result. Of the 53 children with neutralizing antibody, only three were negative in the skin test. The skin test was applied clinically in an institution for mentally retarded children immediately after varicella infection occurred in a patient. A total of 65 patients were examined by the skin test, and 24 children with negative results were given live varicella virus vaccine. As a result, no spread of varicella was observed except for three cases, which developed two weeks after onset of illness in the index case. Thus the skin test seems clinically useful in the determination of susceptibility of individuals to clinical varicella.", "contents": "Diagnostic skin test reactions with varicella virus antigen and clinical application of the test. Varicella virus antigen was prepared and used in skin testing of 75 children one to 17 years old. Results of skin tests were analyzed in relation to history of varicella, presence of absence of neutralizing antibody, and susceptibility to clinical varicella. All 22 children with no history of varicella and no neutralizing antibody were negative in the skin test when an erythematous change of greater than or equal to 5 mm in diameter was taken as a positive result. Of the 53 children with neutralizing antibody, only three were negative in the skin test. The skin test was applied clinically in an institution for mentally retarded children immediately after varicella infection occurred in a patient. A total of 65 patients were examined by the skin test, and 24 children with negative results were given live varicella virus vaccine. As a result, no spread of varicella was observed except for three cases, which developed two weeks after onset of illness in the index case. Thus the skin test seems clinically useful in the determination of susceptibility of individuals to clinical varicella."}
{"id": "PMID:200681", "title": "Cervical excretion cytomegalovirus: correlation with secretory and humoral antibody.", "content": "Cytomegalovirus (CMV) was isolated from cervical secretions of 10 of 121 outpatients at a venereal disease clinic. The buoyant densities of the DNA of five of the 10 CMV isolates were determined and found to be the same as those reported for strains isolated from other anatomical sites. Nine of 102 specimens of cervical secretions were reactive for IgG antibody to CMV, and five of 61 specimens tested were reactive for secretory IgA antibody, whereas two excretors had only IgG and secretory IgA antibody, whereas two excretors had only IgG antibody. Antibody to early antigen was identified in the sera of excretors whose cervical secretions were reactive for IgG and secretory IgA antibody.", "contents": "Cervical excretion cytomegalovirus: correlation with secretory and humoral antibody. Cytomegalovirus (CMV) was isolated from cervical secretions of 10 of 121 outpatients at a venereal disease clinic. The buoyant densities of the DNA of five of the 10 CMV isolates were determined and found to be the same as those reported for strains isolated from other anatomical sites. Nine of 102 specimens of cervical secretions were reactive for IgG antibody to CMV, and five of 61 specimens tested were reactive for secretory IgA antibody, whereas two excretors had only IgG and secretory IgA antibody, whereas two excretors had only IgG antibody. Antibody to early antigen was identified in the sera of excretors whose cervical secretions were reactive for IgG and secretory IgA antibody."}
{"id": "PMID:200688", "title": "A rapid and sensitive radiochemical assay for phosphatidic acid phosphohydrolase activity.", "content": "A technique is described for the radiochemical assay of phosphatidic acid phosphohydrolase activity in rat brain. Radiochemically pure 32P-labeled phosphatidic acid of known specific radioactivity and structure, which was biosynthesized in vitro by the diacylglycerol kinase of E. coli, was used as the substrate. As little as 5 microgram of microsomal or mitochondrial protein can be used for the assay, and product formation in the picomole range can be determined accurately. This procedure should be useful in situations where only limited amounts of tissue are available.", "contents": "A rapid and sensitive radiochemical assay for phosphatidic acid phosphohydrolase activity. A technique is described for the radiochemical assay of phosphatidic acid phosphohydrolase activity in rat brain. Radiochemically pure 32P-labeled phosphatidic acid of known specific radioactivity and structure, which was biosynthesized in vitro by the diacylglycerol kinase of E. coli, was used as the substrate. As little as 5 microgram of microsomal or mitochondrial protein can be used for the assay, and product formation in the picomole range can be determined accurately. This procedure should be useful in situations where only limited amounts of tissue are available."}
{"id": "PMID:200692", "title": "Effect of dibutyryl cyclic AMP and oestradiol on incorporation of [3H]leucine into the proteins of luminal fluid of the rat uterus.", "content": "An injection of 12-5 nmol dibutyryl cyclic AMP (dbcAMP) into each uterine horn of ovariectomized rats maintained on progesterone alone, enhanced incorporation of [3H]leucine into uterine luminal proteins. A value of 11-73 X 10(3) c.p.m.  [3H]leucine incorporated/rat was found after injection of dbcAMP compared with 3-69 X 10(3) c.p.m./rat after injection of saline. An injection of 1-0 microgram oestradiol, in contrast, gave 58-05 X 10(3) c.p.m./rat. Electrophoretic analysis showed that the radioactively labelled proteins found after an injection of dbcAMP or oestradiol were qualitatively similar to those detected on day 5 of pregnancy, the day of blastocyst implantation. The nucleotide thus apparently elicits a uterine response similar to that observed after an injection of oestradiol.", "contents": "Effect of dibutyryl cyclic AMP and oestradiol on incorporation of [3H]leucine into the proteins of luminal fluid of the rat uterus. An injection of 12-5 nmol dibutyryl cyclic AMP (dbcAMP) into each uterine horn of ovariectomized rats maintained on progesterone alone, enhanced incorporation of [3H]leucine into uterine luminal proteins. A value of 11-73 X 10(3) c.p.m.  [3H]leucine incorporated/rat was found after injection of dbcAMP compared with 3-69 X 10(3) c.p.m./rat after injection of saline. An injection of 1-0 microgram oestradiol, in contrast, gave 58-05 X 10(3) c.p.m./rat. Electrophoretic analysis showed that the radioactively labelled proteins found after an injection of dbcAMP or oestradiol were qualitatively similar to those detected on day 5 of pregnancy, the day of blastocyst implantation. The nucleotide thus apparently elicits a uterine response similar to that observed after an injection of oestradiol."}
{"id": "PMID:200693", "title": "Effect of human chorionic gonadotrophin on adenylate cyclase activity and testosterone content in rat testicular mitochondria.", "content": "The adneylate cyclase activity and the concentration of testosterone in testicular mitochondria from immature rats were measured after administration of human chorionic gonadotrophin (HCG) or dibutyryl cyclic AMP in vivo or in vitro. Intratesticular injection of HCG produced an increase in adenylate cyclase activity which preceded the rise in the level of testosterone, whereas addition of the trophic hormone in vitro resulted simultaneous increases. Administration of dibutyryl cyclic AMP in vivo enhanced the testosterone content of the mitochondria. However, the cyclic nucleotide added in vitro at concentrations up to 5 mmol/l had no effect. Cycloheximide injected intraperitoneally before the administration of HCG abolished the stimulatory effect of the trophic hormone on the level of testosterone in the mitochondria, whereas chloramphenicol had no effect. These results, although they confirm the role of cyclic AMP as an intermediate in the stimulatory effect of HCG on the concentration of testosterone in rat testis, do not support a role for mitochondrial adenylate cyclase in this action. A protein regulator(s) formed extramitochondrially appears to be involved in the stimulatory effect of gonadotrophins on steroidogenesis.", "contents": "Effect of human chorionic gonadotrophin on adenylate cyclase activity and testosterone content in rat testicular mitochondria. The adneylate cyclase activity and the concentration of testosterone in testicular mitochondria from immature rats were measured after administration of human chorionic gonadotrophin (HCG) or dibutyryl cyclic AMP in vivo or in vitro. Intratesticular injection of HCG produced an increase in adenylate cyclase activity which preceded the rise in the level of testosterone, whereas addition of the trophic hormone in vitro resulted simultaneous increases. Administration of dibutyryl cyclic AMP in vivo enhanced the testosterone content of the mitochondria. However, the cyclic nucleotide added in vitro at concentrations up to 5 mmol/l had no effect. Cycloheximide injected intraperitoneally before the administration of HCG abolished the stimulatory effect of the trophic hormone on the level of testosterone in the mitochondria, whereas chloramphenicol had no effect. These results, although they confirm the role of cyclic AMP as an intermediate in the stimulatory effect of HCG on the concentration of testosterone in rat testis, do not support a role for mitochondrial adenylate cyclase in this action. A protein regulator(s) formed extramitochondrially appears to be involved in the stimulatory effect of gonadotrophins on steroidogenesis."}
{"id": "PMID:200695", "title": "Testicular receptors for luteinizing hormone after immunoneutralization of gonadotrophin releasing hormone in the male rat.", "content": "The effects of immunoneutralization of endogenous gonadotrophin releasing hormone (GnRH) on the serum concentrations of testosterone and gonadotrophins and the binding of 125I-labelled human chorionic gonadotrophin (HCG) to testicular membrane fractions were studied in adult male rats. Four days after the administration of 1 ml anti-GnRH serum, the level of testosterone in the serum decreased to 44% of the concentration before the injection, whereas administration of normal rabbit serum had no effect. Multiple injections of anti-GnRH serum for 4 days dramatically suppressed the secretion of gonadotrophins in rats orchidectomized 2 months earlier. In intact male rats treated identically, immunoneutralization of GnRH decreased the level of serum testosterone to 32% of the concentration present in saline-treated controls, but did not decrease the number of testicular binding sites for HCG (LH). Administration of testosterone or oestradiol for 3 or 6 days caused a marked reduction in the concentration of serum gonadotrophins but did not decrease the number of LH receptors. This study provides further support for the concept that one releasing hormone governs secretion of both FSH and LH. In addition, these studies indicate that selective reduction of gonadotrophins for 3-6 days has no effect on the number of testicular LH receptors. This suggests that pituitary hormones other than gonadotrophins may be important in the maintenance of testicular receptors for LH.", "contents": "Testicular receptors for luteinizing hormone after immunoneutralization of gonadotrophin releasing hormone in the male rat. The effects of immunoneutralization of endogenous gonadotrophin releasing hormone (GnRH) on the serum concentrations of testosterone and gonadotrophins and the binding of 125I-labelled human chorionic gonadotrophin (HCG) to testicular membrane fractions were studied in adult male rats. Four days after the administration of 1 ml anti-GnRH serum, the level of testosterone in the serum decreased to 44% of the concentration before the injection, whereas administration of normal rabbit serum had no effect. Multiple injections of anti-GnRH serum for 4 days dramatically suppressed the secretion of gonadotrophins in rats orchidectomized 2 months earlier. In intact male rats treated identically, immunoneutralization of GnRH decreased the level of serum testosterone to 32% of the concentration present in saline-treated controls, but did not decrease the number of testicular binding sites for HCG (LH). Administration of testosterone or oestradiol for 3 or 6 days caused a marked reduction in the concentration of serum gonadotrophins but did not decrease the number of LH receptors. This study provides further support for the concept that one releasing hormone governs secretion of both FSH and LH. In addition, these studies indicate that selective reduction of gonadotrophins for 3-6 days has no effect on the number of testicular LH receptors. This suggests that pituitary hormones other than gonadotrophins may be important in the maintenance of testicular receptors for LH."}
{"id": "PMID:200696", "title": "Steroid and prostaglandin concentrations in the plasma of pregnant ewes during infusion of adrenocorticotrophin or dexamethasone to intact or hypophysectomized foetuses.", "content": "Catheters were implanted into 16 ewes and their foetuses between days 110 and 124 of gestation. Hypophysectomy was attempted in eight of these foetuses. Continuous infusion of synthetic ACTH (10 microgram/h) or dexamethasone (1mg/24 h) into the foetus, starting between days 124 and 129, induced premature parturition. The concentration of progesterone in the maternal peripheral plasma decreased before parturition in all animals while the level of oestradiol increased in ewes with intact foetuses or in those in which hypophysectomy was incomplete. When hypophysectomy was complete, no increase in the maternal level of oestradiol occurred before delivery. The concentration of 13,14-dihydro-15-oxo-prostaglandin F2alpha increased in the peripheral plasma of ewes with intact or hypophysectomized foetuses infused with ACTH. It is suggested that an intact foetal pituitary gland is required for the rise in the level of oestrogen prepartum, but that this rise is not essential for increased prostaglandin production of parturition.", "contents": "Steroid and prostaglandin concentrations in the plasma of pregnant ewes during infusion of adrenocorticotrophin or dexamethasone to intact or hypophysectomized foetuses. Catheters were implanted into 16 ewes and their foetuses between days 110 and 124 of gestation. Hypophysectomy was attempted in eight of these foetuses. Continuous infusion of synthetic ACTH (10 microgram/h) or dexamethasone (1mg/24 h) into the foetus, starting between days 124 and 129, induced premature parturition. The concentration of progesterone in the maternal peripheral plasma decreased before parturition in all animals while the level of oestradiol increased in ewes with intact foetuses or in those in which hypophysectomy was incomplete. When hypophysectomy was complete, no increase in the maternal level of oestradiol occurred before delivery. The concentration of 13,14-dihydro-15-oxo-prostaglandin F2alpha increased in the peripheral plasma of ewes with intact or hypophysectomized foetuses infused with ACTH. It is suggested that an intact foetal pituitary gland is required for the rise in the level of oestrogen prepartum, but that this rise is not essential for increased prostaglandin production of parturition."}
{"id": "PMID:200697", "title": "Mammary tumors and mammary tumor virus expression in hybrid mice of strains C57BL and GR.", "content": "Mammary tumorigenesis in genetic crosses between the high mammary tumor incidence GR and the low incidence C57BL mouse strains is highly correlated with murine mammary tumor virus expression in milk. Although the F1 and first backcross females had a mammary tumor incidence which was consistent with a single dominant gene segregation, the tumor incidence in the critical second backcross segregants disproved the single gene hypothesis. Genetic factors were clearly involved in regulation of virus expression which in turn correlated with both tumor incidence and tumor latency; these complex phenotypes are however best explained as threshold or quasicontinuous characters. As predicted from this model, the age specific incidence of mammary tumors showed a broad peak at 14-19 mo of age with no evidence of an early or late phase. Hematopoietic tumors showed no correlation with virus expression or mammary tumorigenesis suggesting different etiologies for these tumors.", "contents": "Mammary tumors and mammary tumor virus expression in hybrid mice of strains C57BL and GR. Mammary tumorigenesis in genetic crosses between the high mammary tumor incidence GR and the low incidence C57BL mouse strains is highly correlated with murine mammary tumor virus expression in milk. Although the F1 and first backcross females had a mammary tumor incidence which was consistent with a single dominant gene segregation, the tumor incidence in the critical second backcross segregants disproved the single gene hypothesis. Genetic factors were clearly involved in regulation of virus expression which in turn correlated with both tumor incidence and tumor latency; these complex phenotypes are however best explained as threshold or quasicontinuous characters. As predicted from this model, the age specific incidence of mammary tumors showed a broad peak at 14-19 mo of age with no evidence of an early or late phase. Hematopoietic tumors showed no correlation with virus expression or mammary tumorigenesis suggesting different etiologies for these tumors."}
{"id": "PMID:200698", "title": "The interaction of Herpes Simplex Virus with murine lymphocytes. I. Mitogenic properties of herpes simplex virus.", "content": "Herpes simplex virus (HSV) stimulates DNA synthesis in mouse spleen cultures prepared from normal, macrophage-depleted, and T-cell-depleted spleen cells, but not from thymocytes. In addition, a polyclonal antibody response is observed in HSV-infected spleen cultures. These findings indicate that the cells stimulated to undergo DNA synthesis after HSV infection appear to be the bone marrow-derived lymphocytes. The newly synthesized DNA is host cell and not of viral origin. Heat treatment and ultraviolet irradiation of HSV before addition to spleen cultures prevents the induction of DNA synthesis. We consider the use of this system as assay for the study of cell transformation by HSV and also for the study of host cell control of the expression of the viral genome.", "contents": "The interaction of Herpes Simplex Virus with murine lymphocytes. I. Mitogenic properties of herpes simplex virus. Herpes simplex virus (HSV) stimulates DNA synthesis in mouse spleen cultures prepared from normal, macrophage-depleted, and T-cell-depleted spleen cells, but not from thymocytes. In addition, a polyclonal antibody response is observed in HSV-infected spleen cultures. These findings indicate that the cells stimulated to undergo DNA synthesis after HSV infection appear to be the bone marrow-derived lymphocytes. The newly synthesized DNA is host cell and not of viral origin. Heat treatment and ultraviolet irradiation of HSV before addition to spleen cultures prevents the induction of DNA synthesis. We consider the use of this system as assay for the study of cell transformation by HSV and also for the study of host cell control of the expression of the viral genome."}
{"id": "PMID:200699", "title": "Secretion of plasminogen activator by human polymorphonuclear leukocytes. Modulation by glucocorticoids and other effectors.", "content": "Purified human PMNs secrete plasminogen activator. This secretion is stimulated by Con A and low concentrations of PMA, and is inhibited by low concentrations of glucocorticoids, and by cAMP, actinomycin D, and cycloheximide. In contrast, the release of granule-bound enzymes, such as elastase, is achieved only at higher concentrations of PMA, and is not affected by any of the inhibitors that block plasminogen activator production. These results show that the production of plasminogen activatory by PMNs is controlled by agents that affect inflammations, and that this control is not shared by other lytic enzymes known to be associated with these cells. This suggests a particular role for plasminogen activator in the response pattern of PMNs and also supports the concept, previously developed for macrophages, that the secretion of this enzyme is correlated with cell migration in vivo.", "contents": "Secretion of plasminogen activator by human polymorphonuclear leukocytes. Modulation by glucocorticoids and other effectors. Purified human PMNs secrete plasminogen activator. This secretion is stimulated by Con A and low concentrations of PMA, and is inhibited by low concentrations of glucocorticoids, and by cAMP, actinomycin D, and cycloheximide. In contrast, the release of granule-bound enzymes, such as elastase, is achieved only at higher concentrations of PMA, and is not affected by any of the inhibitors that block plasminogen activator production. These results show that the production of plasminogen activatory by PMNs is controlled by agents that affect inflammations, and that this control is not shared by other lytic enzymes known to be associated with these cells. This suggests a particular role for plasminogen activator in the response pattern of PMNs and also supports the concept, previously developed for macrophages, that the secretion of this enzyme is correlated with cell migration in vivo."}
{"id": "PMID:200700", "title": "Recovery of avian sarcoma virus from tumors induced by transformation-defective mutants.", "content": "Transformation-defective (td) mutants of the Schmidt-Ruppin strain of Rous sarcoma virus (RSV), which contains deletions in the gene responsible for transformation (src gene), are unable to transform chicken embryo fibroblasts in vitro. Injection of some of these td mutants into newborn chickens resulted in the formation of sarcomas from which sarcoma virus was unfailingly recovered. The possibility that transforming RSV was present in the td virus preparations was excluded by further purification of the td viruses. Morphology of the foci induced by the newly recovered sarcoma virus was distinct from that of foci induced by the parental Schmidt Ruppin strain of RSV. It is suggested that the new sarcoma virus was generated as a result of the genetic interaction between the genomes of td virus and chicken cells.", "contents": "Recovery of avian sarcoma virus from tumors induced by transformation-defective mutants. Transformation-defective (td) mutants of the Schmidt-Ruppin strain of Rous sarcoma virus (RSV), which contains deletions in the gene responsible for transformation (src gene), are unable to transform chicken embryo fibroblasts in vitro. Injection of some of these td mutants into newborn chickens resulted in the formation of sarcomas from which sarcoma virus was unfailingly recovered. The possibility that transforming RSV was present in the td virus preparations was excluded by further purification of the td viruses. Morphology of the foci induced by the newly recovered sarcoma virus was distinct from that of foci induced by the parental Schmidt Ruppin strain of RSV. It is suggested that the new sarcoma virus was generated as a result of the genetic interaction between the genomes of td virus and chicken cells."}
{"id": "PMID:200701", "title": "Inhibition of lymphocyte proliferation stimulated by lectins and allogeneic cells by normal plasma lipoproteins.", "content": "Lipoproteins, isolated by sequential flotation at densities 1.006, 1.019, 1.063, and 1.21, were examined for their ability to inhibit human lymphocytes stimulated by allogeneic cells and by lectins (phytohemagglutinin-P and concanavalin A). All the classes of normal plasma lipoproteins inhibited lymphoproliferation when peripheral blood lymphocytes were cultured in autologous, heterologous, or lipoprotein-deficient plasma (d greater than 1.21). The rank order of inhibitory potency was intermediate density lipoprotein (IDL) greater than very low density lipoproteins (VLDL) greater than low density lipoproteins (LDL) greater than high density lipoproteins (HDL), regardless of the mode of stimulation. The concentrations of IDL, VLDL, and LDL required for complete inhibition of stimulated lymphoproliferation were considerably below the levels of each of these lipoproteins normally found in human plasma. In addition, the concentration of HDL required for 50-90% inhibition was in the range of HDL levels normally found in human plasma. Moreover, at relatively higher concentrations, lipoproteins suppressed the incorporation of [3H]thymidine into DNA below the levels seen with reseting, unstimulated lymphocytes. The results suggest that circulating lymphocytes may normally be highly suppressed by the combined effects of all the endogenous lipoproteins and that the lipoproteins may play important roles in vivo in modulating lymphocyte functions and responses.", "contents": "Inhibition of lymphocyte proliferation stimulated by lectins and allogeneic cells by normal plasma lipoproteins. Lipoproteins, isolated by sequential flotation at densities 1.006, 1.019, 1.063, and 1.21, were examined for their ability to inhibit human lymphocytes stimulated by allogeneic cells and by lectins (phytohemagglutinin-P and concanavalin A). All the classes of normal plasma lipoproteins inhibited lymphoproliferation when peripheral blood lymphocytes were cultured in autologous, heterologous, or lipoprotein-deficient plasma (d greater than 1.21). The rank order of inhibitory potency was intermediate density lipoprotein (IDL) greater than very low density lipoproteins (VLDL) greater than low density lipoproteins (LDL) greater than high density lipoproteins (HDL), regardless of the mode of stimulation. The concentrations of IDL, VLDL, and LDL required for complete inhibition of stimulated lymphoproliferation were considerably below the levels of each of these lipoproteins normally found in human plasma. In addition, the concentration of HDL required for 50-90% inhibition was in the range of HDL levels normally found in human plasma. Moreover, at relatively higher concentrations, lipoproteins suppressed the incorporation of [3H]thymidine into DNA below the levels seen with reseting, unstimulated lymphocytes. The results suggest that circulating lymphocytes may normally be highly suppressed by the combined effects of all the endogenous lipoproteins and that the lipoproteins may play important roles in vivo in modulating lymphocyte functions and responses."}
{"id": "PMID:200702", "title": "The determination of nonesterified fatty acids in blood serum using a stable cupric reagent.", "content": "A modification of the method for the determination of nonesterified fatty acids in blood serum using a stable cupric reagent stabilized with sodium citrate, has been developed. 33 g of NaCl are dissolved in 100 ml of the described reagent, and its pH should not be additionally adjusted. The reagent is stable for at least one year if kept in the refrigerator at 5 degrees C. The determination may be done in 0.1--0.2 ml of blood serum. The relationship between the absorbance and concentration of palmitic acid is still linear at a concentration of 2500 mumol/l. Error of the method is +/- 3%.", "contents": "The determination of nonesterified fatty acids in blood serum using a stable cupric reagent. A modification of the method for the determination of nonesterified fatty acids in blood serum using a stable cupric reagent stabilized with sodium citrate, has been developed. 33 g of NaCl are dissolved in 100 ml of the described reagent, and its pH should not be additionally adjusted. The reagent is stable for at least one year if kept in the refrigerator at 5 degrees C. The determination may be done in 0.1--0.2 ml of blood serum. The relationship between the absorbance and concentration of palmitic acid is still linear at a concentration of 2500 mumol/l. Error of the method is +/- 3%."}
{"id": "PMID:200705", "title": "Virus-induced diabetes mellitus: VIII. Passage of encephalomyocarditis virus and severity of diabetes in susceptible and resistant strains of mice.", "content": "The diabetogenic capacity of the M-variant of encephalomyocarditis (EMC) virus was markedly diminished after passage in mouse kidney cell cultures. One passage in mice fully restored this capacity. Virus harvested after five passages in either susceptible (SWR/J) or resistant (C57BL/6J) strains of mice was capable of producing diabetes in susceptible SWR/J mice but not in resistant C57BL/6J mice. Resistance was not overcome by inoculating mice with high concentrations of virus. Immunofluorescence studies showed that islets from strains of mice (i.e. CBA, AKR, C57BL/6J, A/J) that did not develop diabetes after infection with EMC virus, nonetheless, contained virus antigens. The percentage of cells in the islets containing virus antigens varied from 3-6% in CBA to 13-5% in A/J. In contrast 38% of the islet cells in susceptible SWR/J mice contained virus antigens. It is concluded that both the genetic background of the host and the passage history of the virus influence the development of diabetes.", "contents": "Virus-induced diabetes mellitus: VIII. Passage of encephalomyocarditis virus and severity of diabetes in susceptible and resistant strains of mice. The diabetogenic capacity of the M-variant of encephalomyocarditis (EMC) virus was markedly diminished after passage in mouse kidney cell cultures. One passage in mice fully restored this capacity. Virus harvested after five passages in either susceptible (SWR/J) or resistant (C57BL/6J) strains of mice was capable of producing diabetes in susceptible SWR/J mice but not in resistant C57BL/6J mice. Resistance was not overcome by inoculating mice with high concentrations of virus. Immunofluorescence studies showed that islets from strains of mice (i.e. CBA, AKR, C57BL/6J, A/J) that did not develop diabetes after infection with EMC virus, nonetheless, contained virus antigens. The percentage of cells in the islets containing virus antigens varied from 3-6% in CBA to 13-5% in A/J. In contrast 38% of the islet cells in susceptible SWR/J mice contained virus antigens. It is concluded that both the genetic background of the host and the passage history of the virus influence the development of diabetes."}
{"id": "PMID:200706", "title": "Alterations of actin-containing structures in BHK21 cells infected with Newcastle disease virus and vesicular stomatitis virus.", "content": "The distribution pattern of actin-containing structures in BHK21 cells and the changes which they undergo upon infection with Newcastle disease virus (NDV) and vesicular stomatitis virus (VSV) were studied by means of immunofluorescence. Double labelling with antibodies conjugated with fluorescein (for actin) and rhodamine (for virus antigens) has shown that the progressive cytopathic effects after virus infection are accompanied by extensive alterations of the structures demonstrable by antiactin antibodies. In NDV-infected BHK21 cells the number of actin filaments increases, some zones which contain virus antigens apparently being in close association with the actin structures. By contrast, infection with VSV results in a strong reduction of actin-containing fibres. The results indicate that in the genesis of morphologically detectable alterations of a cell after virus infection--the 'cytopathic changes'--alterations of those structural elements are involved which are also probably responsible for maintenance of cell shape and motility.", "contents": "Alterations of actin-containing structures in BHK21 cells infected with Newcastle disease virus and vesicular stomatitis virus. The distribution pattern of actin-containing structures in BHK21 cells and the changes which they undergo upon infection with Newcastle disease virus (NDV) and vesicular stomatitis virus (VSV) were studied by means of immunofluorescence. Double labelling with antibodies conjugated with fluorescein (for actin) and rhodamine (for virus antigens) has shown that the progressive cytopathic effects after virus infection are accompanied by extensive alterations of the structures demonstrable by antiactin antibodies. In NDV-infected BHK21 cells the number of actin filaments increases, some zones which contain virus antigens apparently being in close association with the actin structures. By contrast, infection with VSV results in a strong reduction of actin-containing fibres. The results indicate that in the genesis of morphologically detectable alterations of a cell after virus infection--the 'cytopathic changes'--alterations of those structural elements are involved which are also probably responsible for maintenance of cell shape and motility."}
{"id": "PMID:200707", "title": "An assessment by competition hybridization of the sequence homology between the RNAs of the seven serotypes of FMDV.", "content": "A comparison has been made of the RNAs of the seven serotypes of foot-and-mouth disease virus (FMDV) by competition hybridization. Homology among the three European serotypes A, O, C and the Asia I serotype was 60 to 70%. Similar homologies were found among the three Southern African Territories serotypes (SAT I, SAT 2, SAT 3), but homology between the two groups was much lower (25 to 40%). Homology between the RNAs of subtypes within serotypes A and O was greater than 70%. Double competition experiments with the Eropean serotypes indicate sharing of nucleotide sequences.", "contents": "An assessment by competition hybridization of the sequence homology between the RNAs of the seven serotypes of FMDV. A comparison has been made of the RNAs of the seven serotypes of foot-and-mouth disease virus (FMDV) by competition hybridization. Homology among the three European serotypes A, O, C and the Asia I serotype was 60 to 70%. Similar homologies were found among the three Southern African Territories serotypes (SAT I, SAT 2, SAT 3), but homology between the two groups was much lower (25 to 40%). Homology between the RNAs of subtypes within serotypes A and O was greater than 70%. Double competition experiments with the Eropean serotypes indicate sharing of nucleotide sequences."}
{"id": "PMID:200708", "title": "Characterization of two distinct molecular populations of type I mouse interferons.", "content": "The molecular heterogeneity of acid-stable (Type I) mouse interferons induced in C243 cells by Newcastle disease virus was analysed by SDS-polyacrylamide gel electrophoresis under non-reducing and reducing conditions, and the profiles of antiviral activities obtained were characterized biologicaly in mouse cells and in heterologous (guinea-pig) cells. Two bands of activity, A and B, were consistently present in all interferon preparations tested: under reducing conditions, the activity in all fractions of band A (with a peak of activity at about 38000 daltons) was uniformly increased, while that of band B (with a peak at about 22000 daltons) was uniformly diminished. All the active fraction in band A had only slight activity (less than 10% of homologous titres) on guinea-pig cells, whereas all those in band B were significantly more active an guinea-pig cells than on homologous L cells. Thus, mouse type I interferon preparations contain two molecular populations of interferons that can be distinguished physically (by size), biochemically (by the effect of reduction on reactivation from SDS) and biologically (by activity in heterologous cells).", "contents": "Characterization of two distinct molecular populations of type I mouse interferons. The molecular heterogeneity of acid-stable (Type I) mouse interferons induced in C243 cells by Newcastle disease virus was analysed by SDS-polyacrylamide gel electrophoresis under non-reducing and reducing conditions, and the profiles of antiviral activities obtained were characterized biologicaly in mouse cells and in heterologous (guinea-pig) cells. Two bands of activity, A and B, were consistently present in all interferon preparations tested: under reducing conditions, the activity in all fractions of band A (with a peak of activity at about 38000 daltons) was uniformly increased, while that of band B (with a peak at about 22000 daltons) was uniformly diminished. All the active fraction in band A had only slight activity (less than 10% of homologous titres) on guinea-pig cells, whereas all those in band B were significantly more active an guinea-pig cells than on homologous L cells. Thus, mouse type I interferon preparations contain two molecular populations of interferons that can be distinguished physically (by size), biochemically (by the effect of reduction on reactivation from SDS) and biologically (by activity in heterologous cells)."}
{"id": "PMID:200710", "title": "Structural studies of encephalomyocarditis virus RNA both in situ and in free solution.", "content": "The secondary structure of encephalomyocarditis (EMC) virus RNA has been studied in situ and in free solution by absorbance-temperature relationships and by circular dichroism (CD). Extracted EMC virus RNA melts reversibly and has a hypochromicity of about 20%; analysis of CD spectra and formaldehyde treatment suggests that approx. 60% of the nucleotides are involved in base-pairing at 25 degrees C. It is shown that the RNA within the virus particle is less structured than when it exists in free solution, being partially stabilized by capsid protein against melting until the virion is disrupted to release the intact RNA. Upon clarification to remove denatured capsid protein, the released RNA gives a melting profile identical with that of phenol-extracted virus RNA. The results suggest that the intact structure of the virus is dependent upon intimate non-covalent bonds between RNA and protein together with hydrophobic bonds between the protein subunits.", "contents": "Structural studies of encephalomyocarditis virus RNA both in situ and in free solution. The secondary structure of encephalomyocarditis (EMC) virus RNA has been studied in situ and in free solution by absorbance-temperature relationships and by circular dichroism (CD). Extracted EMC virus RNA melts reversibly and has a hypochromicity of about 20%; analysis of CD spectra and formaldehyde treatment suggests that approx. 60% of the nucleotides are involved in base-pairing at 25 degrees C. It is shown that the RNA within the virus particle is less structured than when it exists in free solution, being partially stabilized by capsid protein against melting until the virion is disrupted to release the intact RNA. Upon clarification to remove denatured capsid protein, the released RNA gives a melting profile identical with that of phenol-extracted virus RNA. The results suggest that the intact structure of the virus is dependent upon intimate non-covalent bonds between RNA and protein together with hydrophobic bonds between the protein subunits."}
{"id": "PMID:200712", "title": "Avian tumour virus interactions with chicken fibroblast membranes: partial characterization of initial attachment site activity.", "content": "Exposure of chicken embryo fibroblasts (CEF) to trypsin solubilizes cell surface components, including the initial attachment site for avian tumour viruses (ATV). The soluble attachment site activity appears to interact directly with the ATV in vitro thereby interfering with the binding of at least two ATV subgroups to both intact CEF and CEF plasma membranes. A result of this interaction in vitro is reduced ATV infectivity, demonstrated by reduced transforming capacity of RSV (RAV-I).", "contents": "Avian tumour virus interactions with chicken fibroblast membranes: partial characterization of initial attachment site activity. Exposure of chicken embryo fibroblasts (CEF) to trypsin solubilizes cell surface components, including the initial attachment site for avian tumour viruses (ATV). The soluble attachment site activity appears to interact directly with the ATV in vitro thereby interfering with the binding of at least two ATV subgroups to both intact CEF and CEF plasma membranes. A result of this interaction in vitro is reduced ATV infectivity, demonstrated by reduced transforming capacity of RSV (RAV-I)."}
{"id": "PMID:200713", "title": "Scanning electron microscopical observations on the cytopathology of porcine enteroviruses in PK-14 cells.", "content": "Examination by scanning electron microscopy (SEM) of PK-15 cells infected with each of the two cytopathogenic types of porcine enterovirus revealed changes similar to those observed by light microscopy. However, differences between the two types could be detected at an earlier stage of the infection. Cells infected with T80 virus (type I) were rounded, with surface microridges, while V13 (type II) infected cells were characterized by cytoplasmic protrusions.", "contents": "Scanning electron microscopical observations on the cytopathology of porcine enteroviruses in PK-14 cells. Examination by scanning electron microscopy (SEM) of PK-15 cells infected with each of the two cytopathogenic types of porcine enterovirus revealed changes similar to those observed by light microscopy. However, differences between the two types could be detected at an earlier stage of the infection. Cells infected with T80 virus (type I) were rounded, with surface microridges, while V13 (type II) infected cells were characterized by cytoplasmic protrusions."}
{"id": "PMID:200714", "title": "Immunosuppression reactivates and disseminates latent murine cytomegalovirus.", "content": "When searched for by standard virological methods, murine cytomegalovirus (MCMV) becomes undetectable by 4 months after inoculation of mice. However, a 2-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 immunocompromised individuals.", "contents": "Immunosuppression reactivates and disseminates latent murine cytomegalovirus. When searched for by standard virological methods, murine cytomegalovirus (MCMV) becomes undetectable by 4 months after inoculation of mice. However, a 2-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 immunocompromised individuals."}
{"id": "PMID:200715", "title": "Replication of herpes simplex virus DNA after removal of hydroxyurea block from infected cells.", "content": "Hydroxyurea (HU) treatment of HSV-infected cells markedly inhibits the synthesis of virus DNA. Only 0-3.6 of the 3H-thymidine label was incorporated into virus DNA in the presence of HU as compared to untreated infected cells. Removal of HU resulted in a renewed synthesis of virus DNA as determined by the gradual increase in the incorporation of 3H-thymidine into HSV DNA. The labelled virus DNA molecules were isolated and chromatographed on benzoylated napthoylated DEAE (BND)-cellulose columns to separate the replicative intermediates that have single-stranded (ss) sequences from the mature double-stranded (ds) DNA genomes. Mature radioactive dsDNA molecules were found to appear at 22 min after removal of HU and gradually increased in amount thereafter. The virus DNA molecules synthesized during the initial 20 min after removal of HU, constitute the replicative intermediates of HSV DNA. It was calculated that the synthesis of HSV DNA proceeds at the rate of about 5 X 10(6) daltons per min.", "contents": "Replication of herpes simplex virus DNA after removal of hydroxyurea block from infected cells. Hydroxyurea (HU) treatment of HSV-infected cells markedly inhibits the synthesis of virus DNA. Only 0-3.6 of the 3H-thymidine label was incorporated into virus DNA in the presence of HU as compared to untreated infected cells. Removal of HU resulted in a renewed synthesis of virus DNA as determined by the gradual increase in the incorporation of 3H-thymidine into HSV DNA. The labelled virus DNA molecules were isolated and chromatographed on benzoylated napthoylated DEAE (BND)-cellulose columns to separate the replicative intermediates that have single-stranded (ss) sequences from the mature double-stranded (ds) DNA genomes. Mature radioactive dsDNA molecules were found to appear at 22 min after removal of HU and gradually increased in amount thereafter. The virus DNA molecules synthesized during the initial 20 min after removal of HU, constitute the replicative intermediates of HSV DNA. It was calculated that the synthesis of HSV DNA proceeds at the rate of about 5 X 10(6) daltons per min."}
{"id": "PMID:200716", "title": "Observations on the morphology of two rotaviruses.", "content": "The negative staining technique was used to study the morphology of two rotaviruses, the epizootic diarrizootic diarrhoea of infant mice (EDIM) and the simian virus SA II. It is proposed that the inner capsid of the virion has icosahedral symmetry and consists of 180 morphological units arranged in an open lattice formation with the 12 spaces at the apices being surrounded by 5 capsomeres and the other 80 spaces each surrounded by six capsomeres. The outer capsid of the virion consists of a honeycomb-like lattice which corresponds to the lattice arrangement of the inner capsid.", "contents": "Observations on the morphology of two rotaviruses. The negative staining technique was used to study the morphology of two rotaviruses, the epizootic diarrizootic diarrhoea of infant mice (EDIM) and the simian virus SA II. It is proposed that the inner capsid of the virion has icosahedral symmetry and consists of 180 morphological units arranged in an open lattice formation with the 12 spaces at the apices being surrounded by 5 capsomeres and the other 80 spaces each surrounded by six capsomeres. The outer capsid of the virion consists of a honeycomb-like lattice which corresponds to the lattice arrangement of the inner capsid."}
{"id": "PMID:200717", "title": "A micro-electrode study of peripheral neuropathy in man. Part 1. Responses to single graded stimuli.", "content": "Multi-unit micro-electrode recording were obtained from sensory fascicles of the sural and median nerves of 12 control subjects and of 28 patients with peripheral neuropathy. Spontaneous activity and mass responses to mechanical and electrical stimuli were examined. Mechanoreceptor function appeared normal but there was a reduced number of responsive receptors in peripheral neuropathy. The electrical activation threshold of nerve fibres of all conduction velocities was increased in neuropathy and a greater number of fibres needed to be activated for preception to occur. Clinical sensory impairment was associated with a reduction in size of the initial compound action potential of the maximal evoked neurogram and with dispersion of fibre responses. Pathological slowing of fibre conduction velocity was demonstrated in demyelinating neuropathy but in most cases of axomal degeneration the changes in velocity could have been due either to a reduced number of fast conducting fibres, or to conduction block. No changes were observed in C-fibre activity in these patients.", "contents": "A micro-electrode study of peripheral neuropathy in man. Part 1. Responses to single graded stimuli. Multi-unit micro-electrode recording were obtained from sensory fascicles of the sural and median nerves of 12 control subjects and of 28 patients with peripheral neuropathy. Spontaneous activity and mass responses to mechanical and electrical stimuli were examined. Mechanoreceptor function appeared normal but there was a reduced number of responsive receptors in peripheral neuropathy. The electrical activation threshold of nerve fibres of all conduction velocities was increased in neuropathy and a greater number of fibres needed to be activated for preception to occur. Clinical sensory impairment was associated with a reduction in size of the initial compound action potential of the maximal evoked neurogram and with dispersion of fibre responses. Pathological slowing of fibre conduction velocity was demonstrated in demyelinating neuropathy but in most cases of axomal degeneration the changes in velocity could have been due either to a reduced number of fast conducting fibres, or to conduction block. No changes were observed in C-fibre activity in these patients."}
{"id": "PMID:200718", "title": "A micro-electrode study of peripheral neuropathy in man. Part 2. Responses to conditioning stimuli.", "content": "Surface, needle and micro-electrode recordings were obtained from sensory nerves of patients with various types of peripheral neuropathy. Changes in amplitude and conduction velocity of nerve action potentials were measured after a single conditioning stimulus and after tetanic stimulation for 2 min. In patients with hereditary forms of axonal degeneration (AD), recovery processes of nerve fibres of all conduction velocities were normal; in acquired forms of AD fibres with conduction velocity less than 30 m/sec had greater and more prolonged post-tetanic depression than control nerves of similar conduction velocity. Where neuropathy was associated with segmental demyelination (SD), fibres of all conduction velocities had prolonged recovery processes after both single and tetanic stimulation. The changes were especially marked at higher skin temperature, and were greater than the changes seen in nerves with acquired forms of AD. Finally, 2 sural nerves were studied during the process of Wallerian degeneration after a biopsy had been obtained proximally, and recovery processes did not change during the period of degeneration. Perceptual abnormalities were similar in AD and SD. It is suggested that changes in recovery processes of nerve fibres with segmental demyelination or regeneration after injury contribute to the perceptual abnormalities which occur in clinically encountered peripheral neuropathies.", "contents": "A micro-electrode study of peripheral neuropathy in man. Part 2. Responses to conditioning stimuli. Surface, needle and micro-electrode recordings were obtained from sensory nerves of patients with various types of peripheral neuropathy. Changes in amplitude and conduction velocity of nerve action potentials were measured after a single conditioning stimulus and after tetanic stimulation for 2 min. In patients with hereditary forms of axonal degeneration (AD), recovery processes of nerve fibres of all conduction velocities were normal; in acquired forms of AD fibres with conduction velocity less than 30 m/sec had greater and more prolonged post-tetanic depression than control nerves of similar conduction velocity. Where neuropathy was associated with segmental demyelination (SD), fibres of all conduction velocities had prolonged recovery processes after both single and tetanic stimulation. The changes were especially marked at higher skin temperature, and were greater than the changes seen in nerves with acquired forms of AD. Finally, 2 sural nerves were studied during the process of Wallerian degeneration after a biopsy had been obtained proximally, and recovery processes did not change during the period of degeneration. Perceptual abnormalities were similar in AD and SD. It is suggested that changes in recovery processes of nerve fibres with segmental demyelination or regeneration after injury contribute to the perceptual abnormalities which occur in clinically encountered peripheral neuropathies."}
{"id": "PMID:200719", "title": "Spontaneous phagocytosis of boutons on spinal motoneurons during early postnatal development. An electron microscopical study in the cat.", "content": "The boutons making synaptic contact with different regions of spinal motoneurons have been studied during the early postnatal period. The observations suggest that a spontaneous glial phagocytosis of boutons of different types occurs mainly during the second postnatal week. This finding is discussed in relation to the previously demonstrated disappearance of boutons from the initial axon segment of spinal motoneurons during the same period of development and also in relation to other degenerative and eliminatory phenomena associated with the normal development of the nervous system.", "contents": "Spontaneous phagocytosis of boutons on spinal motoneurons during early postnatal development. An electron microscopical study in the cat. The boutons making synaptic contact with different regions of spinal motoneurons have been studied during the early postnatal period. The observations suggest that a spontaneous glial phagocytosis of boutons of different types occurs mainly during the second postnatal week. This finding is discussed in relation to the previously demonstrated disappearance of boutons from the initial axon segment of spinal motoneurons during the same period of development and also in relation to other degenerative and eliminatory phenomena associated with the normal development of the nervous system."}
{"id": "PMID:200720", "title": "Localization of 5-hydroxytryptamine and protein(s) in the secretion granules of the rudimentary photoreceptor cells in the pineal of Lacerta.", "content": "In order to localize 5-hydroxytryptamine (5-HT) stores, the pineal organ of Lacerta was examined by electron microscopy following argentaffin and chromaffin reactions. The results obtained with these ultracytochemical reactions were correlated with those obtained previously using the Falck and Hillarp method and electron microscopic radioautography. The secretion granules (diameter: 60-340 nm) of the secretory rudimentary photoreceptor (SRP) cells are the locus of the argentaffin and chromaffin reactions. The reactivity of the granules disappeared after p-CPA or reserpine administration and increased after nialamide injection. From the previous and present results it can be concluded that 5-HT in the pineal organ of Lacerta is stored in the secretion granules of SRP cells and coexists with a proteinaceous and/or possibly a glycoproteinaceous component. Whether this secretion is neurohormonal in nature is still not clear.", "contents": "Localization of 5-hydroxytryptamine and protein(s) in the secretion granules of the rudimentary photoreceptor cells in the pineal of Lacerta. In order to localize 5-hydroxytryptamine (5-HT) stores, the pineal organ of Lacerta was examined by electron microscopy following argentaffin and chromaffin reactions. The results obtained with these ultracytochemical reactions were correlated with those obtained previously using the Falck and Hillarp method and electron microscopic radioautography. The secretion granules (diameter: 60-340 nm) of the secretory rudimentary photoreceptor (SRP) cells are the locus of the argentaffin and chromaffin reactions. The reactivity of the granules disappeared after p-CPA or reserpine administration and increased after nialamide injection. From the previous and present results it can be concluded that 5-HT in the pineal organ of Lacerta is stored in the secretion granules of SRP cells and coexists with a proteinaceous and/or possibly a glycoproteinaceous component. Whether this secretion is neurohormonal in nature is still not clear."}
{"id": "PMID:200722", "title": "Immunobiology of primary intracranial tumors. Part 3: Microcytotoxicity assays of specific immune responses of brain tumor patients.", "content": "Fifty-six in vitro microcytotoxicity assays were conducted on 30 patients with intracranial tumors at various times during the postoperative course. Significant specific cellular cytotoxic responses were found in nine of 56 assays, humoral cytotoxic responses in nine of 54 assays, and host effector cell-dependent, antibody-dependent cytotoxic responses in four of 28 assays. Variables that might influence the occurrence of cytotoxicity were studied, and the relationship of these findings to other immune parameters was discussed.", "contents": "Immunobiology of primary intracranial tumors. Part 3: Microcytotoxicity assays of specific immune responses of brain tumor patients. Fifty-six in vitro microcytotoxicity assays were conducted on 30 patients with intracranial tumors at various times during the postoperative course. Significant specific cellular cytotoxic responses were found in nine of 56 assays, humoral cytotoxic responses in nine of 54 assays, and host effector cell-dependent, antibody-dependent cytotoxic responses in four of 28 assays. Variables that might influence the occurrence of cytotoxicity were studied, and the relationship of these findings to other immune parameters was discussed."}
{"id": "PMID:200723", "title": "Effect of diet restriction on some key enzymes tryptophan-NAD pathway in rats.", "content": "Dietary intake of rats was restricted by feeding varying amounts of a 20% protein diet. After 6 weeks of feeding, some key enzymes of the tryptophan and nicotinic acid-NAD pathway, liver nicotinamide nucleotide concentration, and urinary metabolites of tryptophan and nicotinic acid were studied. With an increase in diet restriction, liver tryptophan oxygenase (EC 1.13.1.12) activity increased. Quinolinate phosphoribosyltransferase (EC 2.4.2.a) activity, on the other hand, was found to decrease with moderate diet restriction up to 50% restriction, but increased again with more severe diet restriction in rats fed 25% of ad libitum intake. Liver nicotinate phosphoribosyltransferase (EC 2.4.2.11) activity was also observed to decrease with moderate diet restriction and did not further change when the restriction was severe while picolinate carboxylase (EC 4.1.1.45) activity increased significantly only in severe diet restriction. In rats fed 25% of ad libitum intake, urinary quinolinic acid excretion was low whereas N'-methylnicotinamide excretion was elevated. Alterations in the enzyme activities accompanied by changes in the levels of urinary metabolites, observed in the present study, suggest that the potential efficiency of conversion of tryptophan to nicotinamide nucleotides is not constant and is influenced by dietary intake.", "contents": "Effect of diet restriction on some key enzymes tryptophan-NAD pathway in rats. Dietary intake of rats was restricted by feeding varying amounts of a 20% protein diet. After 6 weeks of feeding, some key enzymes of the tryptophan and nicotinic acid-NAD pathway, liver nicotinamide nucleotide concentration, and urinary metabolites of tryptophan and nicotinic acid were studied. With an increase in diet restriction, liver tryptophan oxygenase (EC 1.13.1.12) activity increased. Quinolinate phosphoribosyltransferase (EC 2.4.2.a) activity, on the other hand, was found to decrease with moderate diet restriction up to 50% restriction, but increased again with more severe diet restriction in rats fed 25% of ad libitum intake. Liver nicotinate phosphoribosyltransferase (EC 2.4.2.11) activity was also observed to decrease with moderate diet restriction and did not further change when the restriction was severe while picolinate carboxylase (EC 4.1.1.45) activity increased significantly only in severe diet restriction. In rats fed 25% of ad libitum intake, urinary quinolinic acid excretion was low whereas N'-methylnicotinamide excretion was elevated. Alterations in the enzyme activities accompanied by changes in the levels of urinary metabolites, observed in the present study, suggest that the potential efficiency of conversion of tryptophan to nicotinamide nucleotides is not constant and is influenced by dietary intake."}
{"id": "PMID:200726", "title": "The secretion of adrenal androgens and growth patterns of patients with hypogonadotropic hypogonadism and isiopathic delayed puberty.", "content": "Plasma concentrations of adrenal androgens (DHEA and DHEA-S) and the growth patterns of four male patients with hypogonadotropic hypogonadism have been compared and contrasted with those of eight male patients wit idiopathic delayed puberty. As a group the patients with HH presented at an older age with delayed puberty and normal heights; the growth rate and pattern have been normal except for an absence of the pubertal growth spurt. Adrenal androgens were usually normal for chronologic age and high for bone age. The patients with IDP presented at a younger age, usually with short stature, low adrenal androgens relative to the chronologic age, but normal relative to the bone age. Patients with IDP appear to exhibit a delay in maturation of both the adrenal cortex and the hypothalamo-pituitary gonadal axis usually with short stature and retardation of the bone age. The importance in measurements of adrenal androgens in the diagnosis of HH and of IDP is emphasized.", "contents": "The secretion of adrenal androgens and growth patterns of patients with hypogonadotropic hypogonadism and isiopathic delayed puberty. Plasma concentrations of adrenal androgens (DHEA and DHEA-S) and the growth patterns of four male patients with hypogonadotropic hypogonadism have been compared and contrasted with those of eight male patients wit idiopathic delayed puberty. As a group the patients with HH presented at an older age with delayed puberty and normal heights; the growth rate and pattern have been normal except for an absence of the pubertal growth spurt. Adrenal androgens were usually normal for chronologic age and high for bone age. The patients with IDP presented at a younger age, usually with short stature, low adrenal androgens relative to the chronologic age, but normal relative to the bone age. Patients with IDP appear to exhibit a delay in maturation of both the adrenal cortex and the hypothalamo-pituitary gonadal axis usually with short stature and retardation of the bone age. The importance in measurements of adrenal androgens in the diagnosis of HH and of IDP is emphasized."}
{"id": "PMID:200729", "title": "Chronotropic and cyclic adenosine monophosphate response of fetal rat heart in organ culture to isoproterenol, quinidine, and a dysrhythmogenic agent.", "content": "The fetal rat heart in organ culture was used to investigate rate chanes by various cardioactive agents. Concomitantly, the effect of these pharmacologically induced rate changes on steady-state cyclic adenosine monophosphate levels was determined. Isoproterenol increased the fetal rat heart rate and cyclic adenosine monophosphate in a concentration-related fashion. Quinidine produced a concentration-related decrease in heart rate and no change in cyclic adenosine monophosphate level. The dysrhythmogenic agent produced concentration-related negative chronotropism in the fetal rat heart preparation and significant elevations in cyclic adenosine monophosphate at concentrations without chronotropic action. No correlation between chronotropic effect of a drug and cyclic adenosine monophosphate levels was observed.", "contents": "Chronotropic and cyclic adenosine monophosphate response of fetal rat heart in organ culture to isoproterenol, quinidine, and a dysrhythmogenic agent. The fetal rat heart in organ culture was used to investigate rate chanes by various cardioactive agents. Concomitantly, the effect of these pharmacologically induced rate changes on steady-state cyclic adenosine monophosphate levels was determined. Isoproterenol increased the fetal rat heart rate and cyclic adenosine monophosphate in a concentration-related fashion. Quinidine produced a concentration-related decrease in heart rate and no change in cyclic adenosine monophosphate level. The dysrhythmogenic agent produced concentration-related negative chronotropism in the fetal rat heart preparation and significant elevations in cyclic adenosine monophosphate at concentrations without chronotropic action. No correlation between chronotropic effect of a drug and cyclic adenosine monophosphate levels was observed."}
{"id": "PMID:200730", "title": "Preparation, identification, and quantitative NMR determination of silyl derivatives of 6-aminopenicillanic acid, 7-amino-3-methyl-delta3-cephem-4-carboxylic acid, and 7-amino-3-acetoxymethyl-delta3-cephem-4-carboxylic acid.", "content": "A rapid and accurate method for the quantitative determination of the extent and ratio of amino and carboxyl group trimethylsilylation of 6-aminopenicillanic acid, 7-amino-3-methyl-delta3-cephem-4-carboxylic acid, and 7-amino-3-acetoxymethyl-delta3-cephem-4-carboxylic acid is presented. The method utilizes NMR spectroscopy and is based on the difference in chemical shifts between N-trimethylsilyl and O-trimethylsilyl groups or, in cephalosporin derivatives, between the methyl group in the 3-position and free amino resonances. The spectra of the N,O-bis(trimethylsilyl) derivatives are discussed.", "contents": "Preparation, identification, and quantitative NMR determination of silyl derivatives of 6-aminopenicillanic acid, 7-amino-3-methyl-delta3-cephem-4-carboxylic acid, and 7-amino-3-acetoxymethyl-delta3-cephem-4-carboxylic acid. A rapid and accurate method for the quantitative determination of the extent and ratio of amino and carboxyl group trimethylsilylation of 6-aminopenicillanic acid, 7-amino-3-methyl-delta3-cephem-4-carboxylic acid, and 7-amino-3-acetoxymethyl-delta3-cephem-4-carboxylic acid is presented. The method utilizes NMR spectroscopy and is based on the difference in chemical shifts between N-trimethylsilyl and O-trimethylsilyl groups or, in cephalosporin derivatives, between the methyl group in the 3-position and free amino resonances. The spectra of the N,O-bis(trimethylsilyl) derivatives are discussed."}
{"id": "PMID:200731", "title": "GLC determination of 6-aminopenicillanic acid and 7-amino-3-methyl-delta3-cephem-4-carboxylic acid.", "content": "A quantitative GLC determination of 6-aminopenicillanic acid and 7-amino-3-methyl-delta3-cephem-4-carboxylic acid is presented. The results obtained are in good agreement with those of known chemical procedures. The method is free from interference by related substances.", "contents": "GLC determination of 6-aminopenicillanic acid and 7-amino-3-methyl-delta3-cephem-4-carboxylic acid. A quantitative GLC determination of 6-aminopenicillanic acid and 7-amino-3-methyl-delta3-cephem-4-carboxylic acid is presented. The results obtained are in good agreement with those of known chemical procedures. The method is free from interference by related substances."}
{"id": "PMID:200732", "title": "Antidiarrheal and central nervous system activities of SC-27166 (2-[3 - 5 - methyl - 1, 3, 4 - oxadiazol - 2 - yl) - 3, 3 - diphenylpropyl] - 2 - azabicyclo [2.2.2]octane), a new antidiarrheal agent, resulting from binding to opiate receptor sites of brain and myenteric plexus.", "content": "Pharmacological studies were performed to investigate the interaction of SC-27166 (2-[3-(5-methyl-1,3,4--oxadiazol-2-yl)-3,3-diphenylpropyl]-2-azabicyclo[2.2.2]octane), a new antidiarrheal agent, with opiate receptor sites in vitro and in vivo. Morphine, loperamide and SC-27166 inhibited the binding of [3H]naloxone to homogenates of guinea-pig brain and myenteric plexus and the inhibition was diminished in the presence of 100 mM Na+. Unlike that of morphine and [3H]naloxone itself, the binding of loperamide and SC-27166 was complex and Scatchard plots indicated the presence of low and high affinity sites for both compounds. Morphine, loperamide and SC-27166 inhibited the contractions of electrically driven longitudinal muscle from guinea-pig ileum and naloxone antagonized these effects. In the anesthetized dog, i.v. administration of morphine and SC-27166 enhanced the contractile activity of circular muscle in proximal and distal duodenum and distal ileum but duodenal longitudinal muscle was relaxed; these effects were completely reversed by subsequent administration of naloxone. In the rat, p.o. administration of loperamide and SC-27166 inhibited intestinal propulsion at doses considerably lower than were necessary to produce activity in the hot plate test; this specificity of action was not seen with morphine. In the rat, p.o. administration of loperamide and SC-27166 inhibited diarrhea at doses considerably lower than were necessary to produce withdrawal symptoms. The authors concluded that both loperamide and SC-27166 are specific antidiarrheal agents that produce both their central and antidiarrheal effects by binding to opiate receptor sites.", "contents": "Antidiarrheal and central nervous system activities of SC-27166 (2-[3 - 5 - methyl - 1, 3, 4 - oxadiazol - 2 - yl) - 3, 3 - diphenylpropyl] - 2 - azabicyclo [2.2.2]octane), a new antidiarrheal agent, resulting from binding to opiate receptor sites of brain and myenteric plexus. Pharmacological studies were performed to investigate the interaction of SC-27166 (2-[3-(5-methyl-1,3,4--oxadiazol-2-yl)-3,3-diphenylpropyl]-2-azabicyclo[2.2.2]octane), a new antidiarrheal agent, with opiate receptor sites in vitro and in vivo. Morphine, loperamide and SC-27166 inhibited the binding of [3H]naloxone to homogenates of guinea-pig brain and myenteric plexus and the inhibition was diminished in the presence of 100 mM Na+. Unlike that of morphine and [3H]naloxone itself, the binding of loperamide and SC-27166 was complex and Scatchard plots indicated the presence of low and high affinity sites for both compounds. Morphine, loperamide and SC-27166 inhibited the contractions of electrically driven longitudinal muscle from guinea-pig ileum and naloxone antagonized these effects. In the anesthetized dog, i.v. administration of morphine and SC-27166 enhanced the contractile activity of circular muscle in proximal and distal duodenum and distal ileum but duodenal longitudinal muscle was relaxed; these effects were completely reversed by subsequent administration of naloxone. In the rat, p.o. administration of loperamide and SC-27166 inhibited intestinal propulsion at doses considerably lower than were necessary to produce activity in the hot plate test; this specificity of action was not seen with morphine. In the rat, p.o. administration of loperamide and SC-27166 inhibited diarrhea at doses considerably lower than were necessary to produce withdrawal symptoms. The authors concluded that both loperamide and SC-27166 are specific antidiarrheal agents that produce both their central and antidiarrheal effects by binding to opiate receptor sites."}
{"id": "PMID:200733", "title": "Control of cyclic adenosine 3':5'-monophosphate-elevating effect of adenosine in C-1300 murine neuroblastoma in tissue culture.", "content": "The elevation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) in response to adenosine in C-1300 murine neuroblastoma (clone N2a) in surface culture is increased in magnitude in cultures pretreated overnight with theophylline or adenosine deaminase. This \"potentiating\" effect of theophylline takes time to develop and is blocked by cycloheximide. The cyclic AMP-elevating effect of adenosine decreases in magnitude as the cultures approach confluence. This reduced responsiveness is reversed by the overnight treatment with theophylline. It is hypothesized that adenosine is continually released by the cells to the growth medium and that this adenosine acts extracellularly to modulate the sensitivity of the cells to the cyclic AMP-elevating effect of adenosine.", "contents": "Control of cyclic adenosine 3':5'-monophosphate-elevating effect of adenosine in C-1300 murine neuroblastoma in tissue culture. The elevation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) in response to adenosine in C-1300 murine neuroblastoma (clone N2a) in surface culture is increased in magnitude in cultures pretreated overnight with theophylline or adenosine deaminase. This \"potentiating\" effect of theophylline takes time to develop and is blocked by cycloheximide. The cyclic AMP-elevating effect of adenosine decreases in magnitude as the cultures approach confluence. This reduced responsiveness is reversed by the overnight treatment with theophylline. It is hypothesized that adenosine is continually released by the cells to the growth medium and that this adenosine acts extracellularly to modulate the sensitivity of the cells to the cyclic AMP-elevating effect of adenosine."}
{"id": "PMID:200734", "title": "Protection from habituation of the crayfish lateral giant fibre escape response.", "content": "1. Habituation of the lateral giant fibre escape response in the crayfish to repetitive tactile stimuli is believed to result from homosynaptic depression at the first synapse of the reflex, between tactile afferents and interneurones. Normally, habituation of escape responses to repeated innocuous stimuli is presumed to be adaptive. Experiments reported here were undertaken to determine whether habituation would occur under circumstances when it would presumably be maladaptive - in particular, when tactile receptors are stimulated by an animal's own tail-flip movements.2. Experiments were carried out on the crayfish isolated abdominal nerve cord, which contains the lateral giant reflex pathway.3. Compound e.p.s.p.s elicited in the lateral giant by electrical stimulation of tactile afferents decline by from 25 to 36% over a series of eleven trials at 1/5 sec (control series).4. To determine whether such a decline would occur when sensory afferents are stimulated during a ;tail-flip', stimuli were given as in the control series but each stimulus occurred 20 msec after direct electrical stimulation of a medial giant or lateral giant escape-command fibre at which time tail flexion movements of an intact animal would be in progress. Under these conditions% e.p.s.p. decline over 11 trials at 1/5 sec was only 16-45% of that occurring on the control series.5. This protective effect starts at about 10 msec after escape command neurone firing, is maximal at 20 msec, and thereafter declines, remaining weakly detectable at 100 msec. This time course is commensurate with that required for execution of a tail-flip movement. Thus, sensory afferent-to-lateral giant transmission is protected from depression if stimuli occur when a tail-flip movement is or should be occurring.6. Giant fibre spikes do not superimpose facilitation upon a depressed reflex pathway, nor accelerate rate of recovery from depression; rather, protection is attributable to actual prevention of development of the depressed state.7. Protection was also examined at the first synapse of the reflex, where the depression responsible for habituation is believed to occur, by recording intracellularly in the largest of the first-order interneurones (interneurone A) of the pathway. In absence of protection, ten stimuli presented at 1/4 sec caused a mean decline of 32% in the e.p.s.p. in interneurone A. When such stimuli followed directly evoked escape command neurone firing by 20 msec this decline was reduced by 59-100%.8. We suggest that protection serves to prevent crayfish from habituating to stimuli produced by their own tail-flip movements.", "contents": "Protection from habituation of the crayfish lateral giant fibre escape response. 1. Habituation of the lateral giant fibre escape response in the crayfish to repetitive tactile stimuli is believed to result from homosynaptic depression at the first synapse of the reflex, between tactile afferents and interneurones. Normally, habituation of escape responses to repeated innocuous stimuli is presumed to be adaptive. Experiments reported here were undertaken to determine whether habituation would occur under circumstances when it would presumably be maladaptive - in particular, when tactile receptors are stimulated by an animal's own tail-flip movements.2. Experiments were carried out on the crayfish isolated abdominal nerve cord, which contains the lateral giant reflex pathway.3. Compound e.p.s.p.s elicited in the lateral giant by electrical stimulation of tactile afferents decline by from 25 to 36% over a series of eleven trials at 1/5 sec (control series).4. To determine whether such a decline would occur when sensory afferents are stimulated during a ;tail-flip', stimuli were given as in the control series but each stimulus occurred 20 msec after direct electrical stimulation of a medial giant or lateral giant escape-command fibre at which time tail flexion movements of an intact animal would be in progress. Under these conditions% e.p.s.p. decline over 11 trials at 1/5 sec was only 16-45% of that occurring on the control series.5. This protective effect starts at about 10 msec after escape command neurone firing, is maximal at 20 msec, and thereafter declines, remaining weakly detectable at 100 msec. This time course is commensurate with that required for execution of a tail-flip movement. Thus, sensory afferent-to-lateral giant transmission is protected from depression if stimuli occur when a tail-flip movement is or should be occurring.6. Giant fibre spikes do not superimpose facilitation upon a depressed reflex pathway, nor accelerate rate of recovery from depression; rather, protection is attributable to actual prevention of development of the depressed state.7. Protection was also examined at the first synapse of the reflex, where the depression responsible for habituation is believed to occur, by recording intracellularly in the largest of the first-order interneurones (interneurone A) of the pathway. In absence of protection, ten stimuli presented at 1/4 sec caused a mean decline of 32% in the e.p.s.p. in interneurone A. When such stimuli followed directly evoked escape command neurone firing by 20 msec this decline was reduced by 59-100%.8. We suggest that protection serves to prevent crayfish from habituating to stimuli produced by their own tail-flip movements."}
{"id": "PMID:200735", "title": "Presynaptic inhibition: the mechanism of protection from habituation of the crayfish lateral giant fibre escape response.", "content": "1. Mechanism of protection from habituation of the lateral giant escape reflex of the crayfish was studied. Experiments were designed to determine whether presynaptic inhibition of primary afferents for the reflex occurs following escape command neurone firing, and if so, whether it could account for protection of the first synapse from depression. 2. Synaptic transmission between afferents and interneurone A of the escape reflex is strongly inhibited following giant fibre spikes. 3. Giant fibre firing results in post-synaptic inhibition of interneurone A. However, inhibition of afferent input to interneurone A consistently outlasts both i.p.s.p.s and post-synaptic conductance increases in the neurone; the inhibition, therefore, is probably not exclusively post-synaptic. 4. Giant fibre firing results in excitability changes in sensory afferent terminals as measured by the amplitude of antidromic compound action potentials to focal electrical stimuli applied in the region of afferent terminals in the last abdominal ganglion. The time course of this effect parallels those of protection and inhibition of the first synapse. 5. The magnitude and time course of protection and inhibition of transmission to interneurone A parallel each other closely. Both processes considerably outlast measurable signs of post-synaptic inhibition. 6. We conclude that following giant fibre activity the first synapse of the lateral giant reflex is presynaptically inhibited and the presynaptic inhibition is responsible for the protection effect described in the preceding paper.", "contents": "Presynaptic inhibition: the mechanism of protection from habituation of the crayfish lateral giant fibre escape response. 1. Mechanism of protection from habituation of the lateral giant escape reflex of the crayfish was studied. Experiments were designed to determine whether presynaptic inhibition of primary afferents for the reflex occurs following escape command neurone firing, and if so, whether it could account for protection of the first synapse from depression. 2. Synaptic transmission between afferents and interneurone A of the escape reflex is strongly inhibited following giant fibre spikes. 3. Giant fibre firing results in post-synaptic inhibition of interneurone A. However, inhibition of afferent input to interneurone A consistently outlasts both i.p.s.p.s and post-synaptic conductance increases in the neurone; the inhibition, therefore, is probably not exclusively post-synaptic. 4. Giant fibre firing results in excitability changes in sensory afferent terminals as measured by the amplitude of antidromic compound action potentials to focal electrical stimuli applied in the region of afferent terminals in the last abdominal ganglion. The time course of this effect parallels those of protection and inhibition of the first synapse. 5. The magnitude and time course of protection and inhibition of transmission to interneurone A parallel each other closely. Both processes considerably outlast measurable signs of post-synaptic inhibition. 6. We conclude that following giant fibre activity the first synapse of the lateral giant reflex is presynaptically inhibited and the presynaptic inhibition is responsible for the protection effect described in the preceding paper."}
{"id": "PMID:200736", "title": "Transmission from photoreceptors to ganglion cells in turtle retina.", "content": "1. Synaptic transfer between photoreceptors and impulse-generating cells was studied in isolated eyecups from turtles. Single red-sensitive cones or rods were stimulated by current passed through an intracellular electrode, and impulses generated by the resulting synaptic action were recorded with an external micro-electrode. This technique permits study of retinal transmission without the operation of the visual transduction mechanism. Antidromic stimulation of the optic nerve indicated that most of the impulse-generating cells were ganglion cells.2. Individual ganglion cells responded transiently to changes in the membrane potential of a receptor and could be classified into three groups on the basis of the direction of the effective change in potential. Off centre ganglion cells responded selectively to depolarizations of a receptor, while on centre ganglion cells responded selectively to hyperpolarizations. On-off ganglion cells responded to both depolarizations and hyperpolarizations of a receptor.3. Ganglion cells gave the same pattern of response to electrical hyperpolarization of a receptor and to light in the centre of their receptive fields. Subthreshold depolarizing currents passed in a receptor antagonized the ganglion cell's response to light, and subthreshold hyperpolarizing currents reinforced the response. These observations are consistent with the view that the hyperpolarization generated by visual transduction is responsible for regulating the release of transmitter at the first retinal synapse.4. When a receptor was stimulated with weak current pulses of fixed intensity the number and latency of the ganglion cell impulses fluctuated randomly in successive trials. The relation between the fraction of trials yielding a response and the stimulus intensity was broad. These results indicate that the link between retinal input and output is noisy.5. In the most sensitive pairs of cells, a response of one or more impulses could be obtained in half the trials with a current of about 2 x 10(-11) A, which changed the potential of the receptor by 1-2 mV. A current of similar magnitude would be developed by about 130 photoisomerizations in a red-sensitive cone or 50 photoisomerizations in a rod.6. Dim background light producing a steady hyperpolarization of a few millivolts in the rods raised the threshold for electrically-evoked transmission from a rod to a ganglion cell. In experiments on red-sensitive cones, background light raised the threshold in the off pathway, in which depolarization was the effective stimulus, and lowered the threshold in the on pathway, in which hyperpolarization was the effective stimulus. These changes in sensitivity were not accompanied by obvious changes in the input resistance of the stimulated receptor. Regulation of retinal sensitivity in background light thus involves changes in synaptic transfer as well as changes in the sensitivity of the visual transduction mechanism.", "contents": "Transmission from photoreceptors to ganglion cells in turtle retina. 1. Synaptic transfer between photoreceptors and impulse-generating cells was studied in isolated eyecups from turtles. Single red-sensitive cones or rods were stimulated by current passed through an intracellular electrode, and impulses generated by the resulting synaptic action were recorded with an external micro-electrode. This technique permits study of retinal transmission without the operation of the visual transduction mechanism. Antidromic stimulation of the optic nerve indicated that most of the impulse-generating cells were ganglion cells.2. Individual ganglion cells responded transiently to changes in the membrane potential of a receptor and could be classified into three groups on the basis of the direction of the effective change in potential. Off centre ganglion cells responded selectively to depolarizations of a receptor, while on centre ganglion cells responded selectively to hyperpolarizations. On-off ganglion cells responded to both depolarizations and hyperpolarizations of a receptor.3. Ganglion cells gave the same pattern of response to electrical hyperpolarization of a receptor and to light in the centre of their receptive fields. Subthreshold depolarizing currents passed in a receptor antagonized the ganglion cell's response to light, and subthreshold hyperpolarizing currents reinforced the response. These observations are consistent with the view that the hyperpolarization generated by visual transduction is responsible for regulating the release of transmitter at the first retinal synapse.4. When a receptor was stimulated with weak current pulses of fixed intensity the number and latency of the ganglion cell impulses fluctuated randomly in successive trials. The relation between the fraction of trials yielding a response and the stimulus intensity was broad. These results indicate that the link between retinal input and output is noisy.5. In the most sensitive pairs of cells, a response of one or more impulses could be obtained in half the trials with a current of about 2 x 10(-11) A, which changed the potential of the receptor by 1-2 mV. A current of similar magnitude would be developed by about 130 photoisomerizations in a red-sensitive cone or 50 photoisomerizations in a rod.6. Dim background light producing a steady hyperpolarization of a few millivolts in the rods raised the threshold for electrically-evoked transmission from a rod to a ganglion cell. In experiments on red-sensitive cones, background light raised the threshold in the off pathway, in which depolarization was the effective stimulus, and lowered the threshold in the on pathway, in which hyperpolarization was the effective stimulus. These changes in sensitivity were not accompanied by obvious changes in the input resistance of the stimulated receptor. Regulation of retinal sensitivity in background light thus involves changes in synaptic transfer as well as changes in the sensitivity of the visual transduction mechanism."}
{"id": "PMID:200737", "title": "Kinetics of synaptic transfer from receptors to ganglion cells in turtle retina.", "content": "1. Synaptic transfer between the retinal input and output was studied in turtle eyecups by injecting rectangular current pulses into a single cone or rod while recording externally from a ganglion cell.2. When a receptor was activated with weak steps of polarizing current, the probability of obtaining a ganglion cell impulse rose after an S-shaped delay to a peak at about 0.1 sec and then declined. This suggests that the transmission chain behaves like an electrical band-pass filter containing delay and differentiating elements.3. To further characterize the kinetics of excitation in the subthreshold region, the duration and polarity of the polarizing current pulses were varied while determining the magnitude of the threshold current and the delay to the ganglion cell impulses. The results of these experiments were described with linear models which assume that synaptic transfer occurs over a cascade of first-order delay stages and a single differentiating stage.4. The pathways which relay off responses to light from rods and red-sensitive cones were formally similar, but the time scale in the rod path was several times slower. The path carrying off responses from the red-sensitive cones was faster than the on path. These kinetic differences indicate that independent pathways mediate each of the three categories of response and suggest that the kinetics of each path are ;matched' to the input signals generated by light.5. The strength-latency relations for the responses of on-centre ganglion cells to flashes and steps of light were approximately predicted from the description of synaptic transfer developed here and the description of visual transduction in red-sensitive cones from a previous study.6. It is suggested that the retinal paths have kinetics which might be useful in transmitting light-evoked signals whilst attenuating noise present near the input.", "contents": "Kinetics of synaptic transfer from receptors to ganglion cells in turtle retina. 1. Synaptic transfer between the retinal input and output was studied in turtle eyecups by injecting rectangular current pulses into a single cone or rod while recording externally from a ganglion cell.2. When a receptor was activated with weak steps of polarizing current, the probability of obtaining a ganglion cell impulse rose after an S-shaped delay to a peak at about 0.1 sec and then declined. This suggests that the transmission chain behaves like an electrical band-pass filter containing delay and differentiating elements.3. To further characterize the kinetics of excitation in the subthreshold region, the duration and polarity of the polarizing current pulses were varied while determining the magnitude of the threshold current and the delay to the ganglion cell impulses. The results of these experiments were described with linear models which assume that synaptic transfer occurs over a cascade of first-order delay stages and a single differentiating stage.4. The pathways which relay off responses to light from rods and red-sensitive cones were formally similar, but the time scale in the rod path was several times slower. The path carrying off responses from the red-sensitive cones was faster than the on path. These kinetic differences indicate that independent pathways mediate each of the three categories of response and suggest that the kinetics of each path are ;matched' to the input signals generated by light.5. The strength-latency relations for the responses of on-centre ganglion cells to flashes and steps of light were approximately predicted from the description of synaptic transfer developed here and the description of visual transduction in red-sensitive cones from a previous study.6. It is suggested that the retinal paths have kinetics which might be useful in transmitting light-evoked signals whilst attenuating noise present near the input."}
{"id": "PMID:200738", "title": "Changes in renal cyclic nucleotide content as a possible trigger to the initiation of compensatory renal hypertrophy in rats.", "content": "1. Cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and cyclic guanosine 3', 5'-monophosphate (cyclic GMP) have been estimated in the kidneys of rats.2. Ten minutes after unilateral nephrectomy there was a threefold increase of cyclic GMP in the remaining kidney, which was accompanied by a moderate fall of cyclic AMP.3. The changes in cyclic nucleotides in the remaining kidney after unilateral nephrectomy were of short duration.4. When an anephric rat was cross-circulated with a normal litter-mate, there was an increase of cyclic GMP concentration in the kidneys of the latter, which reached its maximum 10 min after the establishment of the cross circulation.5. In experiments where one kidney of a litter-mate was transplanted to the neck of another rat, unilateral nephrectomy was not followed by changes of the level of cyclic nucleotides in either the transplanted or the remaining kidney. Bilateral nephrectomy, however, resulted in a marked increase of cyclic GMP in the transplanted kidney.6. The clamping of the blood vessels to one kidney for periods up to 10 min had the same effect as unilateral nephrectomy on the concentration of cyclic GMP in the remaining kidney. When the clamp was removed and the circulation restored, the concentrations of cyclic nucleotides returned to preoperative levels in both kidneys.", "contents": "Changes in renal cyclic nucleotide content as a possible trigger to the initiation of compensatory renal hypertrophy in rats. 1. Cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and cyclic guanosine 3', 5'-monophosphate (cyclic GMP) have been estimated in the kidneys of rats.2. Ten minutes after unilateral nephrectomy there was a threefold increase of cyclic GMP in the remaining kidney, which was accompanied by a moderate fall of cyclic AMP.3. The changes in cyclic nucleotides in the remaining kidney after unilateral nephrectomy were of short duration.4. When an anephric rat was cross-circulated with a normal litter-mate, there was an increase of cyclic GMP concentration in the kidneys of the latter, which reached its maximum 10 min after the establishment of the cross circulation.5. In experiments where one kidney of a litter-mate was transplanted to the neck of another rat, unilateral nephrectomy was not followed by changes of the level of cyclic nucleotides in either the transplanted or the remaining kidney. Bilateral nephrectomy, however, resulted in a marked increase of cyclic GMP in the transplanted kidney.6. The clamping of the blood vessels to one kidney for periods up to 10 min had the same effect as unilateral nephrectomy on the concentration of cyclic GMP in the remaining kidney. When the clamp was removed and the circulation restored, the concentrations of cyclic nucleotides returned to preoperative levels in both kidneys."}
{"id": "PMID:200739", "title": "Synaptic excitation and inhibition resulting from direct action of acetylcholine on two types of chemoreceptors on individual amphibian parasympathetic neurones.", "content": "1. Synaptic transmission was studied in visually identified parasympathetic ganglion cells that modulate the heart beat of the mudpuppy Necturus maculosus).2. The brief pulse of acetylcholine (ACh) released from terminals of the vagus nerve after each impulse can produce two distinct post-synaptic responses in individual principal cells of the ganglion: (i) within a milli-second of release, ACh generates a rapid and strong excitatory post-synaptic potential (e.p.s.p.) that normally initiates a post-synaptic impulse; (ii) this excitation is usually followed by a slow hyperpolarizing inhibitory post-synaptic potential (i.p.s.p.) that lasts for several seconds. The magnitude and time course of the i.p.s.p. depends on the frequency and number of vagal stimuli. When the hydrolysis of ACh is inhibited by prostigmine, a train of nerve stimuli may be followed by an i.p.s.p. lasting half a minute or longer.3. The rapid e.p.s.p. and slow i.p.s.p. result from the direct action of ACh on two different types of chemoreceptors in the post-synaptic membrane of the principal cell. The e.p.s.p. can be preferentially blocked by the nicotinic antagonist dihydro-beta-erythroidine (5 x 10(-7)M), while the i.p.s.p. is selectively blocked by the muscarinic antagonist atropine (5 x 10(-9)M).4. Potentials resembling nerve-evoked e.p.s.p.s and i.p.s.p.s can be produced by iontophoretic release of ACh from micropipettes onto the post-synaptic membrane. Application of the muscarinic agonist bethanechol generates exclusively inhibitory responses.5. The reversal potential for the i.p.s.p. is about -105 mV, which is approximately the equilibrium potential for potassium (E(K)). When the external K(+) concentration is altered, the reversal potential for inhibition is shifted to the new value of E(K) as expected from the Nernst equation. Changes in the external Na(+) and Cl(-) concentrations have no appreciable effect on the reversal potential. Thus, the i.p.s.p. is the result of a conductance increase for K(+).6. The conductance change producing the i.p.s.p. is voltage sensitive. When the membrane potential is shifted from -40 to -60 mV, the i.p.s.p becomes larger and longer. Beyond -60 mV the inhibitory response decreases in proportion to the driving force on K(+) without any further change in time course.7. The inhibitory response produced by an iontophoretically applied pulse of bethanechol has a delayed onset of about 150 msec at 24 degrees C. The early portion of this response, including the delay, is proportional to t(3), where t is time. The proportionality factor (the apparent rate constant) decreases elevenfold when the temperature is lowered by 10 degrees C. This suggests that a multi-step process is involved in the activation of the conductance increase that leads to the inhibitory response. Inhibitory responses with similar kinetics were produced in heart muscles of the mudpuppy upon application of ACh.", "contents": "Synaptic excitation and inhibition resulting from direct action of acetylcholine on two types of chemoreceptors on individual amphibian parasympathetic neurones. 1. Synaptic transmission was studied in visually identified parasympathetic ganglion cells that modulate the heart beat of the mudpuppy Necturus maculosus).2. The brief pulse of acetylcholine (ACh) released from terminals of the vagus nerve after each impulse can produce two distinct post-synaptic responses in individual principal cells of the ganglion: (i) within a milli-second of release, ACh generates a rapid and strong excitatory post-synaptic potential (e.p.s.p.) that normally initiates a post-synaptic impulse; (ii) this excitation is usually followed by a slow hyperpolarizing inhibitory post-synaptic potential (i.p.s.p.) that lasts for several seconds. The magnitude and time course of the i.p.s.p. depends on the frequency and number of vagal stimuli. When the hydrolysis of ACh is inhibited by prostigmine, a train of nerve stimuli may be followed by an i.p.s.p. lasting half a minute or longer.3. The rapid e.p.s.p. and slow i.p.s.p. result from the direct action of ACh on two different types of chemoreceptors in the post-synaptic membrane of the principal cell. The e.p.s.p. can be preferentially blocked by the nicotinic antagonist dihydro-beta-erythroidine (5 x 10(-7)M), while the i.p.s.p. is selectively blocked by the muscarinic antagonist atropine (5 x 10(-9)M).4. Potentials resembling nerve-evoked e.p.s.p.s and i.p.s.p.s can be produced by iontophoretic release of ACh from micropipettes onto the post-synaptic membrane. Application of the muscarinic agonist bethanechol generates exclusively inhibitory responses.5. The reversal potential for the i.p.s.p. is about -105 mV, which is approximately the equilibrium potential for potassium (E(K)). When the external K(+) concentration is altered, the reversal potential for inhibition is shifted to the new value of E(K) as expected from the Nernst equation. Changes in the external Na(+) and Cl(-) concentrations have no appreciable effect on the reversal potential. Thus, the i.p.s.p. is the result of a conductance increase for K(+).6. The conductance change producing the i.p.s.p. is voltage sensitive. When the membrane potential is shifted from -40 to -60 mV, the i.p.s.p becomes larger and longer. Beyond -60 mV the inhibitory response decreases in proportion to the driving force on K(+) without any further change in time course.7. The inhibitory response produced by an iontophoretically applied pulse of bethanechol has a delayed onset of about 150 msec at 24 degrees C. The early portion of this response, including the delay, is proportional to t(3), where t is time. The proportionality factor (the apparent rate constant) decreases elevenfold when the temperature is lowered by 10 degrees C. This suggests that a multi-step process is involved in the activation of the conductance increase that leads to the inhibitory response. Inhibitory responses with similar kinetics were produced in heart muscles of the mudpuppy upon application of ACh."}
{"id": "PMID:200741", "title": "[Norepinephrine interference in adrenal hormone balance related to blood calcium effects of PTH (author's transl)].", "content": "Decreased hypercalcemic effects of PTH are observed after medulloadrenalectomy, (table I), metoprione (table II) or cortisone (table IV) treatments in guinea pigs. 2. Norepinephrine restores the blood calcium effects of PTH in these cases but epinephrine is inactive. 3. Immediate activation of kidney adenylate cyclase by PTH (increased urinary AMPc) is also reduced in medulloadrenalectomised, cortisone or metopirone treated guinea pigs (table V). But in this test, norepinephrine reduces the effect of PTH (fig. 1).", "contents": "[Norepinephrine interference in adrenal hormone balance related to blood calcium effects of PTH (author's transl)]. Decreased hypercalcemic effects of PTH are observed after medulloadrenalectomy, (table I), metoprione (table II) or cortisone (table IV) treatments in guinea pigs. 2. Norepinephrine restores the blood calcium effects of PTH in these cases but epinephrine is inactive. 3. Immediate activation of kidney adenylate cyclase by PTH (increased urinary AMPc) is also reduced in medulloadrenalectomised, cortisone or metopirone treated guinea pigs (table V). But in this test, norepinephrine reduces the effect of PTH (fig. 1)."}
{"id": "PMID:200742", "title": "[Placental and fetal growth in the rabbit: influence and mechanism of action of ovarian hormones (author's transl)].", "content": "During the second half of gestation in normal rabbits, hormonal overdoses result in similar modifications of placental and fetal weights, as in castrated animals identically treated (fig. 1). Nucleic acid and protein assays show that hormonal mechanisms are very different for the maternal (table I) and fetal portions of the placenta (table II): progesterone alone promotes a hypertrophy of the fetal placenta and hyperplasia of the maternal placenta. Estradiol at physiological levels counteracts these effects. Moreover, progesterone (fig. 3) and estradiol (fig. 2) receptors are found only in the maternal placenta, although the fetal placental is the most sensitive to the hormonal environment.", "contents": "[Placental and fetal growth in the rabbit: influence and mechanism of action of ovarian hormones (author's transl)]. During the second half of gestation in normal rabbits, hormonal overdoses result in similar modifications of placental and fetal weights, as in castrated animals identically treated (fig. 1). Nucleic acid and protein assays show that hormonal mechanisms are very different for the maternal (table I) and fetal portions of the placenta (table II): progesterone alone promotes a hypertrophy of the fetal placenta and hyperplasia of the maternal placenta. Estradiol at physiological levels counteracts these effects. Moreover, progesterone (fig. 3) and estradiol (fig. 2) receptors are found only in the maternal placenta, although the fetal placental is the most sensitive to the hormonal environment."}
{"id": "PMID:200743", "title": "Problem solving revisited.", "content": "In this paper the increasing problems and need for novel solutions in today's world are discussed. A framework consisting of the combination of the problem-solving process and the creative thinking process is considered. Inherent in each process is a predominant mode of thought: reasoning or vertical thinking in the problem-solving process, and imagination or lateral thinking in the creative thinking process. These processes directed in a complementary manner are suggested as a means of solving problems creatively in situations which call for unique and novel solutions.", "contents": "Problem solving revisited. In this paper the increasing problems and need for novel solutions in today's world are discussed. A framework consisting of the combination of the problem-solving process and the creative thinking process is considered. Inherent in each process is a predominant mode of thought: reasoning or vertical thinking in the problem-solving process, and imagination or lateral thinking in the creative thinking process. These processes directed in a complementary manner are suggested as a means of solving problems creatively in situations which call for unique and novel solutions."}
{"id": "PMID:200747", "title": "A collaborative model for university nursing education and agency staff development.", "content": "A model is proposed for the integration of the education of senior nursing students and staff at a mental hospital, maximizing utilization of time and resources. A pilot study employed small group techniques with faculty as facilitators and resource persons, with the dual purpose of increasing competence and reducing communication barriers. Four students and four nursing staff participated in weekly meetings, alternating supervision groups (2 groups, each composed of 1 faculty, 2 students and 2 staff) with discussion groups (2 faculty, 4 students and 4 staff). Evaluation tools used did not yield significant differences between pre- and post-tests. However, objective and subjective indices point to positive changes of attitudes between all unit staff and students, improved therapeutic skills of students and staff, both on individual and group level. Ongoing group meetings of patients run by students and staff resulted.", "contents": "A collaborative model for university nursing education and agency staff development. A model is proposed for the integration of the education of senior nursing students and staff at a mental hospital, maximizing utilization of time and resources. A pilot study employed small group techniques with faculty as facilitators and resource persons, with the dual purpose of increasing competence and reducing communication barriers. Four students and four nursing staff participated in weekly meetings, alternating supervision groups (2 groups, each composed of 1 faculty, 2 students and 2 staff) with discussion groups (2 faculty, 4 students and 4 staff). Evaluation tools used did not yield significant differences between pre- and post-tests. However, objective and subjective indices point to positive changes of attitudes between all unit staff and students, improved therapeutic skills of students and staff, both on individual and group level. Ongoing group meetings of patients run by students and staff resulted."}
{"id": "PMID:200753", "title": "Microwave fixation of brain tissue as a neurochemical technique- a review.", "content": "Microwave devices have been developed for rapidly inactivating brain enzymes by focusing the power output into the heads of small laboratory animals. The rapid inactivation achieved prevents postmortem changes and permits the measurement of neurochemicals such as acetylcholine at concentrations close to those obtained in vivo. The technique promises the assay of neurochemical parameters not possible before.", "contents": "Microwave fixation of brain tissue as a neurochemical technique- a review. Microwave devices have been developed for rapidly inactivating brain enzymes by focusing the power output into the heads of small laboratory animals. The rapid inactivation achieved prevents postmortem changes and permits the measurement of neurochemicals such as acetylcholine at concentrations close to those obtained in vivo. The technique promises the assay of neurochemical parameters not possible before."}
{"id": "PMID:200754", "title": "Leukocyte migration in ovarian carcinoma: comparison of inhibitory activity of tumor extracts.", "content": "Inhibition of migration of leukocytes from patients with serous cystadenocarcinoma of the ovary was studied by the use of several different types of ovarian carcinoma extract as antigen. KCl extract of an ovarian carconoma was found to be the most effective antigen preparation in comparison with saline, deoxycholate, and perchloric acid extracts. Low concentrations of KCl ovarian carcinoma extract significantly inhibited migration of leukocytes from 11 of 17 patients with ovarian carcinoma (migration index, less than 0.74). Leukocytes from patients with breast, colon, or endometrial carcinoma showed minimal reactivity with ovarian carcinoma KCl extract, and leukocytes from patients with ovarian carcinoma showed minimal reactivity with KCl extracts of breast, colon, and endometrial carcinoma. These results suggested that the 3 M KCl procedure is superior for the isolation of antigens active in the leukocyte migration inhibition test and that this test may be of use for the isolation of tumor-associated antigen and the immunodiagnosis of ovarian carcinoma.", "contents": "Leukocyte migration in ovarian carcinoma: comparison of inhibitory activity of tumor extracts. Inhibition of migration of leukocytes from patients with serous cystadenocarcinoma of the ovary was studied by the use of several different types of ovarian carcinoma extract as antigen. KCl extract of an ovarian carconoma was found to be the most effective antigen preparation in comparison with saline, deoxycholate, and perchloric acid extracts. Low concentrations of KCl ovarian carcinoma extract significantly inhibited migration of leukocytes from 11 of 17 patients with ovarian carcinoma (migration index, less than 0.74). Leukocytes from patients with breast, colon, or endometrial carcinoma showed minimal reactivity with ovarian carcinoma KCl extract, and leukocytes from patients with ovarian carcinoma showed minimal reactivity with KCl extracts of breast, colon, and endometrial carcinoma. These results suggested that the 3 M KCl procedure is superior for the isolation of antigens active in the leukocyte migration inhibition test and that this test may be of use for the isolation of tumor-associated antigen and the immunodiagnosis of ovarian carcinoma."}
{"id": "PMID:200755", "title": "Cytoplasmic leucine naphthylamidase activity expressed in signet-ring cell carcinoma of the stomach.", "content": "Histochemical studies were performed on signet-ring cells in surgically resected gastric carcinomas from 64 patients. On the basis of periodic acid-Schiff reactivity of the intracellular mucin, the signet-ring cells were classified as type A (immature), type B (intermediate), or type C (mature). Different staining reactions to Alcian blue at pH 2.5 enabled type C cells to be subclassified as C-1 or C-2. In 63 cases (98.4%), intense leucine naphthylamidase (LNAase) activity was found histochemically in the cytoplasm of nearly all cancer cells except type C-2. Localization of LNAase activity in the cytoplasm was confirmed by conventional biochemical assay. From the present results, histochemical characteristics of signet-ring cell carcinoma are discussed.", "contents": "Cytoplasmic leucine naphthylamidase activity expressed in signet-ring cell carcinoma of the stomach. Histochemical studies were performed on signet-ring cells in surgically resected gastric carcinomas from 64 patients. On the basis of periodic acid-Schiff reactivity of the intracellular mucin, the signet-ring cells were classified as type A (immature), type B (intermediate), or type C (mature). Different staining reactions to Alcian blue at pH 2.5 enabled type C cells to be subclassified as C-1 or C-2. In 63 cases (98.4%), intense leucine naphthylamidase (LNAase) activity was found histochemically in the cytoplasm of nearly all cancer cells except type C-2. Localization of LNAase activity in the cytoplasm was confirmed by conventional biochemical assay. From the present results, histochemical characteristics of signet-ring cell carcinoma are discussed."}
{"id": "PMID:200756", "title": "Cyclic nucleotide phosphodiesterase and protein activator in human cancer cell lines and Brown-Pearce carcinoma.", "content": "3':5'-Cyclic-AMP phosphodiesterase (EC 3.1.4.17) and the activating factor of cyclic nucleotide phosphodiesterase were detected in cultured human cell lines from patients with lymphoblastic leukemia and retinoblastoma and in the Brown-Pearce (rabbit) carcinoma. The homogenate of lymphoblasts contained levels of the activating factor in excess of that required to produce maximal activation of the endogenous phosphodiesterase. The activating factor found in these malignant cells appears to be similar to the calcium-binding protein activator of bovine brain phosphodiesterase on the basis of the molecular weight obtained from gel filtration, electrophoretic patterns, calcium requirement for the activity, and the effect of calcium on the proteolysis. In addition, the tumor-derived activator was able to restore the activity of activator-deficient phosphodiesterase from the bovine brain.", "contents": "Cyclic nucleotide phosphodiesterase and protein activator in human cancer cell lines and Brown-Pearce carcinoma. 3':5'-Cyclic-AMP phosphodiesterase (EC 3.1.4.17) and the activating factor of cyclic nucleotide phosphodiesterase were detected in cultured human cell lines from patients with lymphoblastic leukemia and retinoblastoma and in the Brown-Pearce (rabbit) carcinoma. The homogenate of lymphoblasts contained levels of the activating factor in excess of that required to produce maximal activation of the endogenous phosphodiesterase. The activating factor found in these malignant cells appears to be similar to the calcium-binding protein activator of bovine brain phosphodiesterase on the basis of the molecular weight obtained from gel filtration, electrophoretic patterns, calcium requirement for the activity, and the effect of calcium on the proteolysis. In addition, the tumor-derived activator was able to restore the activity of activator-deficient phosphodiesterase from the bovine brain."}
{"id": "PMID:200757", "title": "Malignant tumors in rats fed nafenopin, a hepatic peroxisome proliferator.", "content": "Nafenopin (2-methyl-2-[P-(1,2,3,4-tetrahydro-1-naphthyl)phenoxy] propionic acid; Su-13,437), a potent hypolipidemic hepatic peroxisome proliferator, was fed to male F344 rats at a dietary concentration of o.1% until the end of the experiment at 25 months. Between 18 and 25 months, 12 of 15 rats (80%) developed tumors. Approximately 73% (11/15) developed hepatocellular carcinomas, and 10% (3/15) developed pancreatic acinar cell tumors, including 1 metastasizing carcinoma. The hepatocellular carcinomas as well as the acinar cell carcinoma of the pancreas were transplantable successfully through 6 generations.", "contents": "Malignant tumors in rats fed nafenopin, a hepatic peroxisome proliferator. Nafenopin (2-methyl-2-[P-(1,2,3,4-tetrahydro-1-naphthyl)phenoxy] propionic acid; Su-13,437), a potent hypolipidemic hepatic peroxisome proliferator, was fed to male F344 rats at a dietary concentration of o.1% until the end of the experiment at 25 months. Between 18 and 25 months, 12 of 15 rats (80%) developed tumors. Approximately 73% (11/15) developed hepatocellular carcinomas, and 10% (3/15) developed pancreatic acinar cell tumors, including 1 metastasizing carcinoma. The hepatocellular carcinomas as well as the acinar cell carcinoma of the pancreas were transplantable successfully through 6 generations."}
{"id": "PMID:200758", "title": "Cellular immunity to murine sarcoma virus-induced tumors as measured by macrophage migration inhibition assays.", "content": "C57BL/6N mice immunized with regressor murine sarcoma virus (MuSV) were studied at different times after inoculation for their cellular immune responses as measured by migration inhibition assays. We used both the direct capillary and indirect agarose dropiet methods and, as the source of antigens, viable tumor cells and 3 M KCl-solubilized extracts. Migration inhibitory factor (MIF) production coulctivity becoming undetectable after 21 days. However, the level of activity and the kinetics of production of this lymphokine were strongly influenced by the source of the antigen and the form in which it was presented to the immune spleen cells (ISC). Using RBL-5 ct 9-10 days, a decrease to low levels at 14 days, and a second peak of activity between 17 and 21 days. However, uith MBL-2 cells or with 3 M KCl-solubilized antigen from fresh RBL-5 ascites cells, MIF production was observed as early as 9-10 days after tumor induction, peaked at 14 days, and decreased substantially by 21 days. T-cells appeared to be required for migration inhibition reactivity, since ISC depleted of T-lymphocytes by treatment with antibody plus complement were unable to produce MIF after antigen stimulation. The results obtained from specificity studies on the response of ISC in migration inhibition to 11 different tumor lines agreed with the results previously obtained from cytotoxicity studies. With the use of RBL-5 cells as the antigen, there appeared to be an inverse relationship between the development of specific cytotoxic effector cells in 51Cr-release assay and the development of specific effector cells needed for MIF production. However, after removal of adherent cells, the level of cytotoxicity observed correlated with MIF release by immune lymphocytes.", "contents": "Cellular immunity to murine sarcoma virus-induced tumors as measured by macrophage migration inhibition assays. C57BL/6N mice immunized with regressor murine sarcoma virus (MuSV) were studied at different times after inoculation for their cellular immune responses as measured by migration inhibition assays. We used both the direct capillary and indirect agarose dropiet methods and, as the source of antigens, viable tumor cells and 3 M KCl-solubilized extracts. Migration inhibitory factor (MIF) production coulctivity becoming undetectable after 21 days. However, the level of activity and the kinetics of production of this lymphokine were strongly influenced by the source of the antigen and the form in which it was presented to the immune spleen cells (ISC). Using RBL-5 ct 9-10 days, a decrease to low levels at 14 days, and a second peak of activity between 17 and 21 days. However, uith MBL-2 cells or with 3 M KCl-solubilized antigen from fresh RBL-5 ascites cells, MIF production was observed as early as 9-10 days after tumor induction, peaked at 14 days, and decreased substantially by 21 days. T-cells appeared to be required for migration inhibition reactivity, since ISC depleted of T-lymphocytes by treatment with antibody plus complement were unable to produce MIF after antigen stimulation. The results obtained from specificity studies on the response of ISC in migration inhibition to 11 different tumor lines agreed with the results previously obtained from cytotoxicity studies. With the use of RBL-5 cells as the antigen, there appeared to be an inverse relationship between the development of specific cytotoxic effector cells in 51Cr-release assay and the development of specific effector cells needed for MIF production. However, after removal of adherent cells, the level of cytotoxicity observed correlated with MIF release by immune lymphocytes."}
{"id": "PMID:200759", "title": "In vitro inhibition of tritiated thymidine uptake in Morris hepatoma cells by normal rat liver extract: a possible liver chalone.", "content": "A phosphate-buffered saline extract of normal rat liver tissue almost completely inhibited DNA synthesis in Buffalo rat Morris hepatoma 7777 cells in vitro. This effect was tissue-specific because it did not occur with extracts of kidney, spleen, heart, lung, muscle, and hepatoma. The liver extracts did not inhibit in vitro human prostate carcinoma or phytohemagglutinin-stimulated human and rat peripheral blood lymphocyte cultures. The addition of 10% fetal calf serum in the incubation medium had no effect on this inhibition. We determined that doses of liver extract that inhibit thymidine incorporation were not toxic inasmuch as treated cells remained viable, as indicated by trypan blue exclusion. The liver extract may thus contain a cell-specific mitotic inhibitor, a chalone for hepatoma cells.", "contents": "In vitro inhibition of tritiated thymidine uptake in Morris hepatoma cells by normal rat liver extract: a possible liver chalone. A phosphate-buffered saline extract of normal rat liver tissue almost completely inhibited DNA synthesis in Buffalo rat Morris hepatoma 7777 cells in vitro. This effect was tissue-specific because it did not occur with extracts of kidney, spleen, heart, lung, muscle, and hepatoma. The liver extracts did not inhibit in vitro human prostate carcinoma or phytohemagglutinin-stimulated human and rat peripheral blood lymphocyte cultures. The addition of 10% fetal calf serum in the incubation medium had no effect on this inhibition. We determined that doses of liver extract that inhibit thymidine incorporation were not toxic inasmuch as treated cells remained viable, as indicated by trypan blue exclusion. The liver extract may thus contain a cell-specific mitotic inhibitor, a chalone for hepatoma cells."}
{"id": "PMID:200761", "title": "Effect of strain differences and tumor presence on microsomal drug metabolism in the guinea pig: brief communication.", "content": "In vitro drug metabolism in the Hartley guinea pig was compared with that in two inbred guinea pig strains used as carriers for the line 10 hepatoma. We observed minor differences in enzyme specific activity among the three strains. Three weeks after intradermal inoculation of Strain 2 guinea pigs with line 10 hepatoma cells, cytochrome P450 levels and aminopyrine demethylase activity were significantly decreased. Seven to 10 days after inoculation with the ascites form of the tumor, the activities of aniline and biphenyl hydroxylases, p-aminobenzoic acid N-acetyltransferase, and dichloronitrobenzene glutathione S-aryltransferase, in addition to those of cytochrome P450 and aminopyrine N-demethylase, were probably also described.", "contents": "Effect of strain differences and tumor presence on microsomal drug metabolism in the guinea pig: brief communication. In vitro drug metabolism in the Hartley guinea pig was compared with that in two inbred guinea pig strains used as carriers for the line 10 hepatoma. We observed minor differences in enzyme specific activity among the three strains. Three weeks after intradermal inoculation of Strain 2 guinea pigs with line 10 hepatoma cells, cytochrome P450 levels and aminopyrine demethylase activity were significantly decreased. Seven to 10 days after inoculation with the ascites form of the tumor, the activities of aniline and biphenyl hydroxylases, p-aminobenzoic acid N-acetyltransferase, and dichloronitrobenzene glutathione S-aryltransferase, in addition to those of cytochrome P450 and aminopyrine N-demethylase, were probably also described."}
{"id": "PMID:200762", "title": "Induction of hepatic tumors in a teleost (Oryzias latipes) after treatment with methylazoxymethanol acetate: brief communication.", "content": "Liver neoplasms including trabecular hepatoma and cholangioma were induced in medakas (Oryzias latipes) by the addition of methylazoxymethanol acetate to their aquarium water at levels of 0.1-3 ppm for periods ranging from 1 to 120 days. More than 80% of the surviving fish developed tumors at 3 or 5 months after commencement of the treatment, irrespective of levels of the drug, when appropriate times of exposure were chosen.", "contents": "Induction of hepatic tumors in a teleost (Oryzias latipes) after treatment with methylazoxymethanol acetate: brief communication. Liver neoplasms including trabecular hepatoma and cholangioma were induced in medakas (Oryzias latipes) by the addition of methylazoxymethanol acetate to their aquarium water at levels of 0.1-3 ppm for periods ranging from 1 to 120 days. More than 80% of the surviving fish developed tumors at 3 or 5 months after commencement of the treatment, irrespective of levels of the drug, when appropriate times of exposure were chosen."}
{"id": "PMID:200763", "title": "Abrogation of antitumor effects of Corynebacterium parvum and BCG by antimacrophage agents: brief communication.", "content": "The consistently demonstrable antitumor effect of Corynebacterium parvum and BCG against a 7,12-dimethylbenz[a]anthracene-induced rat fibrosarcoma, growing either as a localized subcutaneous tumor or in ascites form, was abrogated by treatment of rats with antimacrophage agents such as silica or carrageenan.", "contents": "Abrogation of antitumor effects of Corynebacterium parvum and BCG by antimacrophage agents: brief communication. The consistently demonstrable antitumor effect of Corynebacterium parvum and BCG against a 7,12-dimethylbenz[a]anthracene-induced rat fibrosarcoma, growing either as a localized subcutaneous tumor or in ascites form, was abrogated by treatment of rats with antimacrophage agents such as silica or carrageenan."}
{"id": "PMID:200764", "title": "Distribution and excretion of 2,4,5,2',4',5'-hexabromobiphenyl, the major component of Firemaster BP-6.", "content": "The intestinal absorption, distribution, and excretion of the major component of Firemaster BP-6,2,4,5,2',4',5'-hexabromobiphenyl, has been studied in the male rat. This polybrominated biphenyl was readily absorbed from the intestine, initially distributed throughout the body, and eventually stored primarily in the adipose tissue, was not subject to appreciable metabolism, and was excreted almost exclusively in the feces and at a very slow rate. Approximately 90% of an oral dose was absorbed from the intestine, and extrapolation of the rate of excretion to infinity indicates that less than 10% of the total dose would ever be excreted.", "contents": "Distribution and excretion of 2,4,5,2',4',5'-hexabromobiphenyl, the major component of Firemaster BP-6. The intestinal absorption, distribution, and excretion of the major component of Firemaster BP-6,2,4,5,2',4',5'-hexabromobiphenyl, has been studied in the male rat. This polybrominated biphenyl was readily absorbed from the intestine, initially distributed throughout the body, and eventually stored primarily in the adipose tissue, was not subject to appreciable metabolism, and was excreted almost exclusively in the feces and at a very slow rate. Approximately 90% of an oral dose was absorbed from the intestine, and extrapolation of the rate of excretion to infinity indicates that less than 10% of the total dose would ever be excreted."}
{"id": "PMID:200766", "title": "Radiation-induced stenosis of the renal artery causing hypertension: case report.", "content": "A case is presented of renal artery stenosis causing renin-dependent hypertension 11 1/2 years after irradiation for Wilms tumor. The literature was reviewed briefly for other cases of large artery damage after irradiation therapy.", "contents": "Radiation-induced stenosis of the renal artery causing hypertension: case report. A case is presented of renal artery stenosis causing renin-dependent hypertension 11 1/2 years after irradiation for Wilms tumor. The literature was reviewed briefly for other cases of large artery damage after irradiation therapy."}
{"id": "PMID:200767", "title": "Hepatoma in a child with methotrexate-induced hepatic fibrosis.", "content": "During autopsy, an 11-year-old girl with acute lymphocytic leukemia was found to have hepatic fibrosis with a 2.5-cm nodule of hepatocarcinoma. For 5 1/2 of the six years of treatment, chemotherapy consisted of daily orally administered methotrexate with monthly doses of vincristine sulfate and prednisone. The cumulative dose of methotrexate was 2.5 g. To our knowledge, this report constitutes the first association of hepatoma with methotrexate-induced hepatic fibrosis. A careful follow-up of patients receiving methotrexate for malignant neoplasms is urged; caution is suggested in the prolonged use of methotrexate when treating benign disease.", "contents": "Hepatoma in a child with methotrexate-induced hepatic fibrosis. During autopsy, an 11-year-old girl with acute lymphocytic leukemia was found to have hepatic fibrosis with a 2.5-cm nodule of hepatocarcinoma. For 5 1/2 of the six years of treatment, chemotherapy consisted of daily orally administered methotrexate with monthly doses of vincristine sulfate and prednisone. The cumulative dose of methotrexate was 2.5 g. To our knowledge, this report constitutes the first association of hepatoma with methotrexate-induced hepatic fibrosis. A careful follow-up of patients receiving methotrexate for malignant neoplasms is urged; caution is suggested in the prolonged use of methotrexate when treating benign disease."}
{"id": "PMID:200784", "title": "[Myocardial function in patients with congenital pulmonary valve stenosis].", "content": "The studies of metabolism and morphology of the myocardium, and of ECG parameters in 72 patients with valvular pulmonary stenosis conducted with biopsy and autopsy material has demonstrated that while the workload on the right ventricle grows and the severity of the pathological process increases, the oxidative capacity of the myocardium also increase, the indices of its energy supply decrease, the degree of myocytes hypertrophy grows, and the number of mitochondria and the coefficient of their energy efficacy decrease. A correlation was established between the degree of these changes and the severity of electrocardiographic signs of hypertrophy and disorders in the repolarization process in the right ventricle.", "contents": "[Myocardial function in patients with congenital pulmonary valve stenosis]. The studies of metabolism and morphology of the myocardium, and of ECG parameters in 72 patients with valvular pulmonary stenosis conducted with biopsy and autopsy material has demonstrated that while the workload on the right ventricle grows and the severity of the pathological process increases, the oxidative capacity of the myocardium also increase, the indices of its energy supply decrease, the degree of myocytes hypertrophy grows, and the number of mitochondria and the coefficient of their energy efficacy decrease. A correlation was established between the degree of these changes and the severity of electrocardiographic signs of hypertrophy and disorders in the repolarization process in the right ventricle."}
{"id": "PMID:200785", "title": "[Study of the mechanisms of adrenaline effect on the coupling of respiration with phosphorylation and K+ content in the cardiac mitochondria].", "content": "The binding of Ca2+ with fatty acids during the isolation of mitochondria from a conine heart was shown not to prevent the dissociation of respiration and physphorylation produced by adrenalin. The proteinkinase activated by cyclic AMP participates in the dissociation of respiration and phosphorylation in the mitochondria when adrenalin is administered in vivo. The reduced K+ content in the mitochondria under the effect of adrenalin is attributed to a reduction of the membrane potential of the mitochondria, the passive permeability of the mitochondria for K+ ions remaining unchanged.", "contents": "[Study of the mechanisms of adrenaline effect on the coupling of respiration with phosphorylation and K+ content in the cardiac mitochondria]. The binding of Ca2+ with fatty acids during the isolation of mitochondria from a conine heart was shown not to prevent the dissociation of respiration and physphorylation produced by adrenalin. The proteinkinase activated by cyclic AMP participates in the dissociation of respiration and phosphorylation in the mitochondria when adrenalin is administered in vivo. The reduced K+ content in the mitochondria under the effect of adrenalin is attributed to a reduction of the membrane potential of the mitochondria, the passive permeability of the mitochondria for K+ ions remaining unchanged."}
{"id": "PMID:200786", "title": "[Hydroxyproline content in blood and urine in ischemic heart disease].", "content": "The content of protein-bound oxyproline in blood and the total oxyproline content in urine were studied in 70 healthy individuals between the ages of 20 and 60 and in 124 patients with chronic ischemic heart disease whose ages ranged from 32 to 74. No age dependence of the protein-bound oxyproline level in blood plasma was revealed in healthy individuals. The concentration of oxyproline excreted in the urine was higher in individuals between the ages of 20 and 30 than among older individuals. In patients with chronic ischemic heart disease the level of protein-bound oxyproline in blood plasma  was normal, excretion of oxyproline with the urine was increased. In patients with myocardial infarction a period of increased content of oxyproline in blood and urine was observed, the duration of which was determined by the extent and depth of infarction and the clinical course of the disease.", "contents": "[Hydroxyproline content in blood and urine in ischemic heart disease]. The content of protein-bound oxyproline in blood and the total oxyproline content in urine were studied in 70 healthy individuals between the ages of 20 and 60 and in 124 patients with chronic ischemic heart disease whose ages ranged from 32 to 74. No age dependence of the protein-bound oxyproline level in blood plasma was revealed in healthy individuals. The concentration of oxyproline excreted in the urine was higher in individuals between the ages of 20 and 30 than among older individuals. In patients with chronic ischemic heart disease the level of protein-bound oxyproline in blood plasma  was normal, excretion of oxyproline with the urine was increased. In patients with myocardial infarction a period of increased content of oxyproline in blood and urine was observed, the duration of which was determined by the extent and depth of infarction and the clinical course of the disease."}
{"id": "PMID:200789", "title": "[The diagnostic value of corneal arcus as symptom of hyperlipoproteinemia (author's transl)].", "content": "In the normal population a physiologic arcus senilis develops in the 6th and the following decades. Hyperlipoproteinemia (type II a  and type II b) however may be the cause of an earlier onset of a corneal arcus. 63 patients with hyperlipoproteinemia type II a and type II b were examined with slit-lamp. In more than 75% of these patients corneal arcus were found already in the 5th decade. Normal population of the same age in contrast shows an arcus corneae only in 25%. Prospective examinations of the Western Collaborative Group found out, that men, 39-49 years old, had with corneal arcus a significantly higher incidence of coronary heart disease, compared with those without arcus. The average annual incidence of symptomatic myocardial infarction was 6.8 per 1000 with arcus as compared to 3.2 per 1000 without. In the 6th decade however there was no more any difference between subjects with arcus and those without arcus. These results, together with the findings of our study, show that one ought to examine the blood-lipids, if by chance of the first refraction a fully developed arcus corneae is found.", "contents": "[The diagnostic value of corneal arcus as symptom of hyperlipoproteinemia (author's transl)]. In the normal population a physiologic arcus senilis develops in the 6th and the following decades. Hyperlipoproteinemia (type II a  and type II b) however may be the cause of an earlier onset of a corneal arcus. 63 patients with hyperlipoproteinemia type II a and type II b were examined with slit-lamp. In more than 75% of these patients corneal arcus were found already in the 5th decade. Normal population of the same age in contrast shows an arcus corneae only in 25%. Prospective examinations of the Western Collaborative Group found out, that men, 39-49 years old, had with corneal arcus a significantly higher incidence of coronary heart disease, compared with those without arcus. The average annual incidence of symptomatic myocardial infarction was 6.8 per 1000 with arcus as compared to 3.2 per 1000 without. In the 6th decade however there was no more any difference between subjects with arcus and those without arcus. These results, together with the findings of our study, show that one ought to examine the blood-lipids, if by chance of the first refraction a fully developed arcus corneae is found."}
{"id": "PMID:200790", "title": "[Perimetry in chiasmal syndrome -Liminal and surpraliminal stimuli (author's transl)].", "content": "The value of static and kinetic perimetry with white and colored stimuli in chiasmal syndrome seems to be equal. The presentation of evenly moving supraliminal targets allows for an evaluation of sensory disturbance. This procedure is even more subjective, variable and difficult to perform accurately. It may reveal, however, more discrete sensory pathology than conventional perimetry can do. Red is often better than other colors, spectral colors are better than pigment colors. The sector-shaped pattern of disturbance of sensation might relfect the arrangement of nerve-fibers in the optic chiasm.", "contents": "[Perimetry in chiasmal syndrome -Liminal and surpraliminal stimuli (author's transl)]. The value of static and kinetic perimetry with white and colored stimuli in chiasmal syndrome seems to be equal. The presentation of evenly moving supraliminal targets allows for an evaluation of sensory disturbance. This procedure is even more subjective, variable and difficult to perform accurately. It may reveal, however, more discrete sensory pathology than conventional perimetry can do. Red is often better than other colors, spectral colors are better than pigment colors. The sector-shaped pattern of disturbance of sensation might relfect the arrangement of nerve-fibers in the optic chiasm."}
{"id": "PMID:200791", "title": "[The use of photon absorptiometry in renal osteodystrophy (author's transl)].", "content": "In 58 patients with end-stage renal failure before commencement of regular hemodialyses treatment (RTD) and 58 patients under RTD bone mineral content (BMC) was determined by the use of the photon absorptiometry. Further the effect of a treatment with bitamin D3 and 5,6-trans-25-OH-vitamin D3 on BMC was studied. There existed a negative correlation between the duration of chronic renal failure or of RDT as well as of the serum parathyroid hormone level to BMC. No correlation was found between BMC and serum calcium level. During a 14 months-course treatment with vitamin D3 or 5,6-trans-25-OH-vitamin D3 BMC increased. The method of photon absorptiometry presented itself as an easy and well reproducible technique for routine examinations.", "contents": "[The use of photon absorptiometry in renal osteodystrophy (author's transl)]. In 58 patients with end-stage renal failure before commencement of regular hemodialyses treatment (RTD) and 58 patients under RTD bone mineral content (BMC) was determined by the use of the photon absorptiometry. Further the effect of a treatment with bitamin D3 and 5,6-trans-25-OH-vitamin D3 on BMC was studied. There existed a negative correlation between the duration of chronic renal failure or of RDT as well as of the serum parathyroid hormone level to BMC. No correlation was found between BMC and serum calcium level. During a 14 months-course treatment with vitamin D3 or 5,6-trans-25-OH-vitamin D3 BMC increased. The method of photon absorptiometry presented itself as an easy and well reproducible technique for routine examinations."}
{"id": "PMID:200792", "title": "Evaluation of the classical methods for the diagnosis of type III hyperlipoproteinemia.", "content": "Familial type III hyperlipoproteinemia is characterized by the presence of elevated plasma levels of very low density lopoproteins (VLDL) which contain an increased amount of cholesterol and by the presence of a significant amount of lipoproteins with an intermediate density between that of VLDL and low density lipoproteins (LDL); the intermediate density lopoproteins, designated IDL or Lp III, have a slower electrophoretic migration rate than VLDL, and are found in the ultracentrifugal top fraction as a contaminant. Classically, the diagnosis of type III is based on the demonstration of beta-migrating lipoproteins in the ultracentrifugal top fraction (density less than 1.006), thus \"floating beta-lipoprotein\". More recently, it has been proposed that an elevated VLDL-cholesterol to triglyceride ratio is diagnostic of the disorder. In the present report, we have compared the two methods for their diagnostic value and have concluded that the chemical index definition is the more reliable method for the diagnosis of type III hyperlipoproteinemia.", "contents": "Evaluation of the classical methods for the diagnosis of type III hyperlipoproteinemia. Familial type III hyperlipoproteinemia is characterized by the presence of elevated plasma levels of very low density lopoproteins (VLDL) which contain an increased amount of cholesterol and by the presence of a significant amount of lipoproteins with an intermediate density between that of VLDL and low density lipoproteins (LDL); the intermediate density lopoproteins, designated IDL or Lp III, have a slower electrophoretic migration rate than VLDL, and are found in the ultracentrifugal top fraction as a contaminant. Classically, the diagnosis of type III is based on the demonstration of beta-migrating lipoproteins in the ultracentrifugal top fraction (density less than 1.006), thus \"floating beta-lipoprotein\". More recently, it has been proposed that an elevated VLDL-cholesterol to triglyceride ratio is diagnostic of the disorder. In the present report, we have compared the two methods for their diagnostic value and have concluded that the chemical index definition is the more reliable method for the diagnosis of type III hyperlipoproteinemia."}
{"id": "PMID:200815", "title": "Hypercholesterolemia and triglyceride secretion rates in monkeys fed different dietary fats.", "content": "The influence of hypercholesterolemia on the triglyceride secretion rate was studied in both squirrel and cebus monkeys fed coconut oil, corn oil, or safflower oil. The triglyceride secretion rate (TGSR) was determined in vivo following the administration of Triton WR1339, which blocks the clearance of very low density lipoprotein (VLDL). Thus, the increase observed in circulating triglyceride after Triton administration presumably reflecte hepatic triglyceride (VLDL) secretion in the fasted state. The VLDL-TGSR was lowest in hypercholesterolemic monkeys and highest in those fed unsaturated fat diets and having a low serum cholesterol. In all instances, TGSR was inversely correlated with the plasma cholesterol concentration. While a definitive explanation for these observations must await further investigation, the possibility that circulating low density lipoprotein (LDL) acts to feed back on VLDL secretion is discussed. The decreased TGSR associated with the diet-induced cholesterolemia also implies clearance of VLDL is impaired under these conditions.", "contents": "Hypercholesterolemia and triglyceride secretion rates in monkeys fed different dietary fats. The influence of hypercholesterolemia on the triglyceride secretion rate was studied in both squirrel and cebus monkeys fed coconut oil, corn oil, or safflower oil. The triglyceride secretion rate (TGSR) was determined in vivo following the administration of Triton WR1339, which blocks the clearance of very low density lipoprotein (VLDL). Thus, the increase observed in circulating triglyceride after Triton administration presumably reflecte hepatic triglyceride (VLDL) secretion in the fasted state. The VLDL-TGSR was lowest in hypercholesterolemic monkeys and highest in those fed unsaturated fat diets and having a low serum cholesterol. In all instances, TGSR was inversely correlated with the plasma cholesterol concentration. While a definitive explanation for these observations must await further investigation, the possibility that circulating low density lipoprotein (LDL) acts to feed back on VLDL secretion is discussed. The decreased TGSR associated with the diet-induced cholesterolemia also implies clearance of VLDL is impaired under these conditions."}
{"id": "PMID:200816", "title": "Autoxidation of fatty acid monolayers adsorbed on silica gel: I. Nature of adsorption sites.", "content": "An unsaturated fatty acid monolayer deposited on a silica gel surface has been chosen as a model for studying non-enzymatic autoxidation of membrane lipids. Studies to determine the suitability of this system as a model for biomembranes were conducted to define the nature of the monolayers, particularly with respect to the factors determining the concentration of the fatty acid molecule on unit area of the surface. The results from adsorption isotherm, high temperature dehydroxylation, and infrared spectra studies show that adsorption of a monomolecular layer of fatty acids occurs and that the number of molecules absorbed corresponds to the number of isolated, non-hydrogen-bonded silanol groups. It is presumed the binding is by hydrogen bonding of the carboxyl groups to silanol groups. The packing density of the fatty acid molecules is 1.25 molecule/100 A2 which is similar to the density of the isolated silanol sites on the surface.", "contents": "Autoxidation of fatty acid monolayers adsorbed on silica gel: I. Nature of adsorption sites. An unsaturated fatty acid monolayer deposited on a silica gel surface has been chosen as a model for studying non-enzymatic autoxidation of membrane lipids. Studies to determine the suitability of this system as a model for biomembranes were conducted to define the nature of the monolayers, particularly with respect to the factors determining the concentration of the fatty acid molecule on unit area of the surface. The results from adsorption isotherm, high temperature dehydroxylation, and infrared spectra studies show that adsorption of a monomolecular layer of fatty acids occurs and that the number of molecules absorbed corresponds to the number of isolated, non-hydrogen-bonded silanol groups. It is presumed the binding is by hydrogen bonding of the carboxyl groups to silanol groups. The packing density of the fatty acid molecules is 1.25 molecule/100 A2 which is similar to the density of the isolated silanol sites on the surface."}
{"id": "PMID:200817", "title": "Autoxidation of fatty acid monolayers adsorbed on silica gel: II. Rates and products.", "content": "Unsaturated fatty acid monolayers on silica gel have been autoxidized, and the rate of fatty acid disappearance and products obtained from those membrane-like assemblies have been studied. Fatty acid monolayers consisting of pure linoleic acid, linolelaidic acid, and oleic acid were autoxidized at 60 C. The rates of autoxidation of linoleic acid and linolelaidic acid monolayers followed by the disappearance of substrates are considerably faster than that in bulk phase, and the rates conform to apparent first order kinetics. Autoxidation of linoleic and linolelaidic acid monolayers, unlike bulk phase, produced only a small amount of diene conjugation, and the major products formed were identified as 9,10-epoxy and 12,13-epoxyoctadecenoic acid in roughly equal quantities. The epoxidation is stereospecific, with cis and trans olefins giving cis and trans epoxides, respectively. Oleic acid was autoxidized to only a small extent during 27 hr and produced no detectable amount of epoxide.", "contents": "Autoxidation of fatty acid monolayers adsorbed on silica gel: II. Rates and products. Unsaturated fatty acid monolayers on silica gel have been autoxidized, and the rate of fatty acid disappearance and products obtained from those membrane-like assemblies have been studied. Fatty acid monolayers consisting of pure linoleic acid, linolelaidic acid, and oleic acid were autoxidized at 60 C. The rates of autoxidation of linoleic acid and linolelaidic acid monolayers followed by the disappearance of substrates are considerably faster than that in bulk phase, and the rates conform to apparent first order kinetics. Autoxidation of linoleic and linolelaidic acid monolayers, unlike bulk phase, produced only a small amount of diene conjugation, and the major products formed were identified as 9,10-epoxy and 12,13-epoxyoctadecenoic acid in roughly equal quantities. The epoxidation is stereospecific, with cis and trans olefins giving cis and trans epoxides, respectively. Oleic acid was autoxidized to only a small extent during 27 hr and produced no detectable amount of epoxide."}
{"id": "PMID:200827", "title": "Effect of polymyxin B on outer membranes of Serratia marcescens: morphological alterations of the outer membranes and their lipopolysaccharide components.", "content": "The in vitro or the in vivo treatment of outer membranes and their lipopolysaccharide (LPS) components from Serratia marcescens with the antibiotic polymyxin B appeared to alter their normal morphology in a sequential manner. The normal spherodial morphology was destablized into a flattened structure after the in vitro treatment of either the resistant strain 08 or the sensitive strain Bizio. The more severe in vivo treatment of the outer membranes from the resistant strain converted the flattened forms further into spheres with undefined periphery and diminished sizes. On the other hand, the same treatment of the outer membranes from the sensitive strain resulted in numerous incomplete spheres and short rods, which were similar to the various morphological forms of the LPS components after polymyxin B treatment. The difference in the morphological changes of the outer membranes and their LPS components of the resistant and sensitive strains after polymyxin B treatment may be explained by the variation of the susceptiblity of the membrane components to the degradative effects of the antibiotic.", "contents": "Effect of polymyxin B on outer membranes of Serratia marcescens: morphological alterations of the outer membranes and their lipopolysaccharide components. The in vitro or the in vivo treatment of outer membranes and their lipopolysaccharide (LPS) components from Serratia marcescens with the antibiotic polymyxin B appeared to alter their normal morphology in a sequential manner. The normal spherodial morphology was destablized into a flattened structure after the in vitro treatment of either the resistant strain 08 or the sensitive strain Bizio. The more severe in vivo treatment of the outer membranes from the resistant strain converted the flattened forms further into spheres with undefined periphery and diminished sizes. On the other hand, the same treatment of the outer membranes from the sensitive strain resulted in numerous incomplete spheres and short rods, which were similar to the various morphological forms of the LPS components after polymyxin B treatment. The difference in the morphological changes of the outer membranes and their LPS components of the resistant and sensitive strains after polymyxin B treatment may be explained by the variation of the susceptiblity of the membrane components to the degradative effects of the antibiotic."}
{"id": "PMID:200832", "title": "Leukemia following Reye's syndrome treated with exchange transfusions: search for type-C viral infection.", "content": "A 5-year-old child developed acute lymphoblastic leukemia during convalescence from an episode of Reye's syndrome that was treated with multiple exchange transfusions. Routine laboratory, histology, and viral serology were unable to establish a common etiology for the 2 illnesses. Cultural and immunologic methods to search for evidence of infection with type-C viruses or viral genes in lymphoblasts from the buffy coat and bone marrow failed to reveal these agents. Although no common infectious etiology was defined for the close temporal occurrence of 2 rare diseases, the possibility of an iatrogenically induced malignancy was considered.", "contents": "Leukemia following Reye's syndrome treated with exchange transfusions: search for type-C viral infection. A 5-year-old child developed acute lymphoblastic leukemia during convalescence from an episode of Reye's syndrome that was treated with multiple exchange transfusions. Routine laboratory, histology, and viral serology were unable to establish a common etiology for the 2 illnesses. Cultural and immunologic methods to search for evidence of infection with type-C viruses or viral genes in lymphoblasts from the buffy coat and bone marrow failed to reveal these agents. Although no common infectious etiology was defined for the close temporal occurrence of 2 rare diseases, the possibility of an iatrogenically induced malignancy was considered."}
{"id": "PMID:200835", "title": "Ertosterol biosynthesis in Saccharomyces cerevisiae: mutants deficient in the early steps of the pathway.", "content": "Thermosensitive mutants, auxotrophic for ergosterol synthesis, have been isolated, analyzed genetically and their enzymatic deficiencies investigated. These mutants were classified into seven unlinked complementation groups. These groupes lack the following enzymatic activities: squalene epoxidase (erg 1), 2,3-oxidosqualene-lanosterol cyclase (erg 7), phosphomevalonic kinase (erg 8), mevalonic kinase (erg12) and squalene synthetase (erg 9, erg 10, erg 11).", "contents": "Ertosterol biosynthesis in Saccharomyces cerevisiae: mutants deficient in the early steps of the pathway. Thermosensitive mutants, auxotrophic for ergosterol synthesis, have been isolated, analyzed genetically and their enzymatic deficiencies investigated. These mutants were classified into seven unlinked complementation groups. These groupes lack the following enzymatic activities: squalene epoxidase (erg 1), 2,3-oxidosqualene-lanosterol cyclase (erg 7), phosphomevalonic kinase (erg 8), mevalonic kinase (erg12) and squalene synthetase (erg 9, erg 10, erg 11)."}
{"id": "PMID:200836", "title": "On the structure of the deo operon of Escherichia coli.", "content": "A characterization of a specialized transducing lambda phage for the deo operon (lambdaddeo), and some composite colE1-deo plasmids is given in this paper. This includes localization of the RSmaI, RHind/III, RBamI, and REcoRI sensitive sites. The deo genes have been localized by construction of composite colE1-deo plasmids. Using the DNA fragments, obtained by digestion with REcoRI and RHindIII, respectively, as templates in an in vitro protein synthesizing system, it has been possible to give the direction of transcription and the exact location of the deo genes, relative to the endonuclease sites. Furthermore, the cytO,P and deoO,P regions have been mapped relative to the structural genes. Supercoiled co1E1-deo DNA has been used as template in the in vitro system; this DNA gives essentially the same results as the endonuclease-fragmented DNA. The use of the different types of templates is discussed.", "contents": "On the structure of the deo operon of Escherichia coli. A characterization of a specialized transducing lambda phage for the deo operon (lambdaddeo), and some composite colE1-deo plasmids is given in this paper. This includes localization of the RSmaI, RHind/III, RBamI, and REcoRI sensitive sites. The deo genes have been localized by construction of composite colE1-deo plasmids. Using the DNA fragments, obtained by digestion with REcoRI and RHindIII, respectively, as templates in an in vitro protein synthesizing system, it has been possible to give the direction of transcription and the exact location of the deo genes, relative to the endonuclease sites. Furthermore, the cytO,P and deoO,P regions have been mapped relative to the structural genes. Supercoiled co1E1-deo DNA has been used as template in the in vitro system; this DNA gives essentially the same results as the endonuclease-fragmented DNA. The use of the different types of templates is discussed."}
{"id": "PMID:200838", "title": "Uridine-cytidine kinase. III. Competition between uridine and cytidine for a single enzyme.", "content": "The combined phosphorylation of uridine and cytidine by a partially purified preparation of uridine-cytidine kinase has been studied with dual-substrate kinetics. The kinetic patterns obtained are consistent with the theoretical analysis for two competing, alternate substrates interacting with a single enzyme. Thus, despite feedback regulation of the kinase by both UTP and CTP, the results allow a clear conclusion that both nucleosides are phosphorylated by the same enzyme, and probably at a single site, rather than by two closely related isozymes, each specific for one pyrimidine.", "contents": "Uridine-cytidine kinase. III. Competition between uridine and cytidine for a single enzyme. The combined phosphorylation of uridine and cytidine by a partially purified preparation of uridine-cytidine kinase has been studied with dual-substrate kinetics. The kinetic patterns obtained are consistent with the theoretical analysis for two competing, alternate substrates interacting with a single enzyme. Thus, despite feedback regulation of the kinase by both UTP and CTP, the results allow a clear conclusion that both nucleosides are phosphorylated by the same enzyme, and probably at a single site, rather than by two closely related isozymes, each specific for one pyrimidine."}
{"id": "PMID:200839", "title": "[Classification and supervision of hyperlipemias (author's transl)].", "content": "Different methods for determination and classification systems of serum lipoproteins were used and compared in 300 patients with hyperlipidemia. The procedures and methods were examined to find out which would provide a useful classification for diagnosis and therapy. Lipid electrophoresis on agarose gel gave no reliably reproducible typing. With acetate and polyacetate foils, Type llb was not recognizable in the majority of cases. Neither the determination of beta-cholesterol after polyanion precipitation nor quantitative lipid electrophoresis calculating the values as lipoprotein lipid gave type determinations which completely agreed with the ultracentrifuge, but the best coincidence with the ultracentrifuge was obtained with these two methods. The second method is chiefly suitable for supervision.", "contents": "[Classification and supervision of hyperlipemias (author's transl)]. Different methods for determination and classification systems of serum lipoproteins were used and compared in 300 patients with hyperlipidemia. The procedures and methods were examined to find out which would provide a useful classification for diagnosis and therapy. Lipid electrophoresis on agarose gel gave no reliably reproducible typing. With acetate and polyacetate foils, Type llb was not recognizable in the majority of cases. Neither the determination of beta-cholesterol after polyanion precipitation nor quantitative lipid electrophoresis calculating the values as lipoprotein lipid gave type determinations which completely agreed with the ultracentrifuge, but the best coincidence with the ultracentrifuge was obtained with these two methods. The second method is chiefly suitable for supervision."}
{"id": "PMID:200837", "title": "Glycosphingolipid hydrolases: properties and molecular genetics.", "content": "This is a review of the properties and molecular genetics of six lysosomal hydrolases: beta-galactosidase, hexosaminidases A and B, alpha-galactosidase, beta-glucosidase and alpha-fucosidase. Each enzyme is discussed with regards to isoenzymes and substrate specificity, subunit structure, genetic relationship of isoenzymes and genetic variants. The molecular genetics of human diseases caused by deficiencies of each enzyme are discussed.", "contents": "Glycosphingolipid hydrolases: properties and molecular genetics. This is a review of the properties and molecular genetics of six lysosomal hydrolases: beta-galactosidase, hexosaminidases A and B, alpha-galactosidase, beta-glucosidase and alpha-fucosidase. Each enzyme is discussed with regards to isoenzymes and substrate specificity, subunit structure, genetic relationship of isoenzymes and genetic variants. The molecular genetics of human diseases caused by deficiencies of each enzyme are discussed."}
{"id": "PMID:200840", "title": "[Operative possibilities for tumors in single kidneys with particular reference to in situ perfusion (author's transl)].", "content": "Surgical removal of malignant tumors from a single kidney is definitely a problem which can be solved by modern techniques of urological surgery. The different operation techniques in 5 of the patients operated on in the Urologische Universit\u00e4tsklinik Giessen are presented and discussed. In the individual case, besides extracorporeal tumor surgery, the excision of the tumor especially using in situ perfusion with the aid of the floating catheter can facilitate the surgical intervention considerably, and in particular reduce the danger of a postoperative renal failure.", "contents": "[Operative possibilities for tumors in single kidneys with particular reference to in situ perfusion (author's transl)]. Surgical removal of malignant tumors from a single kidney is definitely a problem which can be solved by modern techniques of urological surgery. The different operation techniques in 5 of the patients operated on in the Urologische Universit\u00e4tsklinik Giessen are presented and discussed. In the individual case, besides extracorporeal tumor surgery, the excision of the tumor especially using in situ perfusion with the aid of the floating catheter can facilitate the surgical intervention considerably, and in particular reduce the danger of a postoperative renal failure."}
{"id": "PMID:200841", "title": "Selective deficiency of hepatic triglyceride lipase in uremic patients.", "content": "To investigate the pathogenesis of hypertriglyceridemia in patients with renal disease we measured plasma lipoprotein composition as well as hepatic triglyceride lipase and lipoprotein lipase in post-heparin plasma. Three groups with renal disease were studied: conservatively treated chronic uremia; patients undergoing maintenance hemodialysis; and renal-allograft recipients. A selective decrease of hepatic triglyceride lipase with normal lipoprotein lipase was found in conservatively treated uremia and in patients undergoing hemodialysis. Elevated levels of very-low-density lipoproteins and increased triglycerides in low-density lipoproteins occurred in these patients. In contrast, hepatic triglyceride lipase and lipoprotein lipase were both normal in patients after renal transplantation who had Type II hyperlipoproteinemia as a common lipoprotein pattern with increased low-density-lipoprotein cholesterol and decreased high-density-lipoprotein cholesterol concentrations. The accumulation of a triglyceride-rich low-density lipoprotein in the majority of patients with renal disease may be the consequence of low hepatic triglyceride lipase.", "contents": "Selective deficiency of hepatic triglyceride lipase in uremic patients. To investigate the pathogenesis of hypertriglyceridemia in patients with renal disease we measured plasma lipoprotein composition as well as hepatic triglyceride lipase and lipoprotein lipase in post-heparin plasma. Three groups with renal disease were studied: conservatively treated chronic uremia; patients undergoing maintenance hemodialysis; and renal-allograft recipients. A selective decrease of hepatic triglyceride lipase with normal lipoprotein lipase was found in conservatively treated uremia and in patients undergoing hemodialysis. Elevated levels of very-low-density lipoproteins and increased triglycerides in low-density lipoproteins occurred in these patients. In contrast, hepatic triglyceride lipase and lipoprotein lipase were both normal in patients after renal transplantation who had Type II hyperlipoproteinemia as a common lipoprotein pattern with increased low-density-lipoprotein cholesterol and decreased high-density-lipoprotein cholesterol concentrations. The accumulation of a triglyceride-rich low-density lipoprotein in the majority of patients with renal disease may be the consequence of low hepatic triglyceride lipase."}
{"id": "PMID:200843", "title": "Malakoplakia: evidence for monocyte lysosomal abnormality correctable by cholinergic agonist in vitro and in vivo.", "content": "We studied monocyte function in a case of malakoplakia in an attempt to characterize the immune defect in this condition. Our patient's intracellular cyclic-GMP levels were abnormally low (mean +/- S.D. of 0.17 +/- 0.05 pmol per 10(7) malakoplakia cells, versus 0.79 +/- 0.12 in normals) p less than 0.001). After phagocytosis, his monocytes failed to release beta-glucuronidase. In the bactericidal assay, incubation of the patient's monocytes with Escherichia coli allowed growth of 542 +/- 46 colonies, normal monocytes allowed 95 +/- 22 (p less than 0.001). The percentage of monocytes with large lysosomal granules was 23 +/- 4 in the patient and 4 +/- 2 in normal controls. After in vitro incubation of the patient's cells or in vivo treatment with bethanechol chloride, the cyclic-GMP levels, bactericidal ability and lysosomal granules of the cells returned to normal levels. Low levels of cyclic-GMP could impair lysosomal function and bacterial killing in this condition. Cholinergic agonists correct the in vitro abnormalities and are beneficial in vivo.", "contents": "Malakoplakia: evidence for monocyte lysosomal abnormality correctable by cholinergic agonist in vitro and in vivo. We studied monocyte function in a case of malakoplakia in an attempt to characterize the immune defect in this condition. Our patient's intracellular cyclic-GMP levels were abnormally low (mean +/- S.D. of 0.17 +/- 0.05 pmol per 10(7) malakoplakia cells, versus 0.79 +/- 0.12 in normals) p less than 0.001). After phagocytosis, his monocytes failed to release beta-glucuronidase. In the bactericidal assay, incubation of the patient's monocytes with Escherichia coli allowed growth of 542 +/- 46 colonies, normal monocytes allowed 95 +/- 22 (p less than 0.001). The percentage of monocytes with large lysosomal granules was 23 +/- 4 in the patient and 4 +/- 2 in normal controls. After in vitro incubation of the patient's cells or in vivo treatment with bethanechol chloride, the cyclic-GMP levels, bactericidal ability and lysosomal granules of the cells returned to normal levels. Low levels of cyclic-GMP could impair lysosomal function and bacterial killing in this condition. Cholinergic agonists correct the in vitro abnormalities and are beneficial in vivo."}
{"id": "PMID:200844", "title": "Synchronised transmembrane insertion and glycosylation of a nascent membrane protein.", "content": "Studies of the synthesis and incorporation of the vesicular stomatitis virus glycoprotein into membranes in a synchronised cell-free system demonstrate a tight coupling between polypeptide synthesis and membrane insertion, as a result of which the nascent chain crosses the membrane. The studies reveal a surprisingly precise sequence by which the nascent chain of this membrane glycoprotein is glycosylated in two steps. These findings have important implications for the mechanisms of membrane assembly.", "contents": "Synchronised transmembrane insertion and glycosylation of a nascent membrane protein. Studies of the synthesis and incorporation of the vesicular stomatitis virus glycoprotein into membranes in a synchronised cell-free system demonstrate a tight coupling between polypeptide synthesis and membrane insertion, as a result of which the nascent chain crosses the membrane. The studies reveal a surprisingly precise sequence by which the nascent chain of this membrane glycoprotein is glycosylated in two steps. These findings have important implications for the mechanisms of membrane assembly."}
{"id": "PMID:200850", "title": "[Molecular biology of tumor viruses].", "content": "All classes of vertebrates harbor tumor viruses that are capable of inducing either tumors or leukemias. After infection, their genomes become integral parts of the host cell's genetic material (DNA). Many biological functions such as the capacity to code for the synthesis of new proteins and, in particular, the oncogenic property (oncogen) have already been assigned to specific regions (on physical maps) of their DNA.", "contents": "[Molecular biology of tumor viruses]. All classes of vertebrates harbor tumor viruses that are capable of inducing either tumors or leukemias. After infection, their genomes become integral parts of the host cell's genetic material (DNA). Many biological functions such as the capacity to code for the synthesis of new proteins and, in particular, the oncogenic property (oncogen) have already been assigned to specific regions (on physical maps) of their DNA."}
{"id": "PMID:200852", "title": "Effects of type A botulinum toxin on the cholinergic transmission at spinal Renshaw cells and on the inhibitory action at Ia inhibitory interneurones.", "content": "1. The central action of botulinum toxin A (BTA) on the cholinergic transmission at Renshaw cells (RCs) and on the RC-induced inhibition of Ia inhibitory interneurones (IaINs) was studied in anaesthetized cats. BTA was administered by application directly into the spinal cord, injection into a ventral root (L7) and/or injection into the triceps surae (GS) muscle. 2. A direct application of BTA into the spinal cord led to a decrease of the early and the late response of RCs. 3. When the neurotoxin was injected into the GS muscle, the RC activity remained unaffected during the test period (33-46 h after application). 4. No effect appeared up to 10 h after an injection into the ventral root L7. 5. The RC-induced inhibition on IaINs, when tested in animals with local botulismus, remained intact during the test period. 6. From the present results it is suggested that on the spinal level the central action of botulinum toxin predominantly passes on the motoneurones.", "contents": "Effects of type A botulinum toxin on the cholinergic transmission at spinal Renshaw cells and on the inhibitory action at Ia inhibitory interneurones. 1. The central action of botulinum toxin A (BTA) on the cholinergic transmission at Renshaw cells (RCs) and on the RC-induced inhibition of Ia inhibitory interneurones (IaINs) was studied in anaesthetized cats. BTA was administered by application directly into the spinal cord, injection into a ventral root (L7) and/or injection into the triceps surae (GS) muscle. 2. A direct application of BTA into the spinal cord led to a decrease of the early and the late response of RCs. 3. When the neurotoxin was injected into the GS muscle, the RC activity remained unaffected during the test period (33-46 h after application). 4. No effect appeared up to 10 h after an injection into the ventral root L7. 5. The RC-induced inhibition on IaINs, when tested in animals with local botulismus, remained intact during the test period. 6. From the present results it is suggested that on the spinal level the central action of botulinum toxin predominantly passes on the motoneurones."}
{"id": "PMID:200857", "title": "[Electrotonic and chemical EPSPs in lamprey motor neurons following stimulation of the descending tract and posterior root afferents].", "content": "In experiments carried out on the isolated spinal cord of the lamprey (Lampetra fluviatilis) post-synaptic responses produced in spinal motoneurons by stimulation of the descending tract and dorsal roots were investigated by means of the intracellular recording technique. It is found that, in addition to giant reticulospinal (M\u00fcller's) axons, many other descending fibres as well as dorsal root afferents establish synaptic linkage with both chemical and electrical mode of transmission as revealed by their sensitivity to calcium-deficient and magnesium-rich perfusing solutions. Complex electrotonic EPSPs could have a very fast time course characteristic for the elementary responses but could also produce slow depolarization of the post-synaptic membrane, thus suggesting an integrative function of electrical synapses.", "contents": "[Electrotonic and chemical EPSPs in lamprey motor neurons following stimulation of the descending tract and posterior root afferents]. In experiments carried out on the isolated spinal cord of the lamprey (Lampetra fluviatilis) post-synaptic responses produced in spinal motoneurons by stimulation of the descending tract and dorsal roots were investigated by means of the intracellular recording technique. It is found that, in addition to giant reticulospinal (M\u00fcller's) axons, many other descending fibres as well as dorsal root afferents establish synaptic linkage with both chemical and electrical mode of transmission as revealed by their sensitivity to calcium-deficient and magnesium-rich perfusing solutions. Complex electrotonic EPSPs could have a very fast time course characteristic for the elementary responses but could also produce slow depolarization of the post-synaptic membrane, thus suggesting an integrative function of electrical synapses."}
{"id": "PMID:200858", "title": "Enzymes relevant to cancer chemotherapy II. Heterogeneity of rat kidney uridine kinase following chromatography on Sepharose 6B coupled to N4-(5-amino-Pentyl)-cytidine.", "content": "Using Sepharose 6B coupled to N4-(5-aminopentyl)-cytidine at least three different peaks of rat kidney uridine kinase activity have been found. Prior to affinity chromatography the enzyme was partially purified by ammonium sulfate precipitation. The elution was carried out with 0.15 M NaCl or with 0.012 M ATP. The importance of different forms of uridine kinase in eukaryotic cells for cancer chemotherapy with uridine and cytidine analogues is discussed.", "contents": "Enzymes relevant to cancer chemotherapy II. Heterogeneity of rat kidney uridine kinase following chromatography on Sepharose 6B coupled to N4-(5-amino-Pentyl)-cytidine. Using Sepharose 6B coupled to N4-(5-aminopentyl)-cytidine at least three different peaks of rat kidney uridine kinase activity have been found. Prior to affinity chromatography the enzyme was partially purified by ammonium sulfate precipitation. The elution was carried out with 0.15 M NaCl or with 0.012 M ATP. The importance of different forms of uridine kinase in eukaryotic cells for cancer chemotherapy with uridine and cytidine analogues is discussed."}
{"id": "PMID:200859", "title": "Mitochondrial ATPase of Zajdela hepatoma. II. Mitochondria of Zajdela hepatoma contain less adenosine triphosphatase than mitochondria of rat liver.", "content": "The specific activity and the content of ATPase in mitochondria of rat liver and Zajdela hepatoma were compared. The specific activity of ATPase in sonicated mitochondria and in mitochondrial membrane fraction of rat liver was almost two times higher than the specific activity in the corresponding fraction of Zajdela hepatoma. Accordingly, the autovertin binding capacity of rat liver mitochondrial membrane fraction as well as the yield of F1-ATPase from this fraction were about two times higher than those of the mitochondrial membrane fraction of Zajdela hepatoma. The results show that mitochondria of Zajdela Hapatoma possess about half amount of ATPase present in rat liver mitochondria.", "contents": "Mitochondrial ATPase of Zajdela hepatoma. II. Mitochondria of Zajdela hepatoma contain less adenosine triphosphatase than mitochondria of rat liver. The specific activity and the content of ATPase in mitochondria of rat liver and Zajdela hepatoma were compared. The specific activity of ATPase in sonicated mitochondria and in mitochondrial membrane fraction of rat liver was almost two times higher than the specific activity in the corresponding fraction of Zajdela hepatoma. Accordingly, the autovertin binding capacity of rat liver mitochondrial membrane fraction as well as the yield of F1-ATPase from this fraction were about two times higher than those of the mitochondrial membrane fraction of Zajdela hepatoma. The results show that mitochondria of Zajdela Hapatoma possess about half amount of ATPase present in rat liver mitochondria."}
{"id": "PMID:200860", "title": "Effect of hematin in porphyric neuropathy.", "content": "Early, intravenous administration of hematin in a patient with acute intermittent porphyria and severe quadriparesis may have produced partial but remarkable improvement of neuropathy, and resulted in simultaneous decline of porphyrin precursors in the blood. Intermittent, biweekly hematin infusions given 1 month after the onset of the porphyric relapse had no effect on recovery of the residual neuropathy. We believe hematin may be effective in the treatment of porphyric neuropathy, if administered before irreversible neuronal damage has occured.", "contents": "Effect of hematin in porphyric neuropathy. Early, intravenous administration of hematin in a patient with acute intermittent porphyria and severe quadriparesis may have produced partial but remarkable improvement of neuropathy, and resulted in simultaneous decline of porphyrin precursors in the blood. Intermittent, biweekly hematin infusions given 1 month after the onset of the porphyric relapse had no effect on recovery of the residual neuropathy. We believe hematin may be effective in the treatment of porphyric neuropathy, if administered before irreversible neuronal damage has occured."}
{"id": "PMID:200861", "title": "Adrenomyeloneuropathy: a probable variant of adrenoleukodystrophy. I. Clinical and endocrinologic aspects.", "content": "We have studied four unrelated males with a heritable disorder that we term adrenomyeloneuropathy; limited clinical information is available on a fifth case. All had adrenal insufficiency beginning in childhood and developed progressive spastic paraparesis in the third decade. Hypogonadism of variable severity was present in all four cases appropriately examined. Neurologic features included peripheral neuropathy, impotence, and sphincter disturbances. Late manifestations were cerebellar dysfunction in one case and dementia and hemiparesis in another. A family history of adrenal disease or spastic paraparesis was present in two cases and absent in one; in the other two, no family history was available. Although males are predominantly affected, the mode of inheritance is uncertain. Adrenomyeloneuropathy probably represents a clinically and genetically distinct variant of childhood adrenoleukodystrophy.", "contents": "Adrenomyeloneuropathy: a probable variant of adrenoleukodystrophy. I. Clinical and endocrinologic aspects. We have studied four unrelated males with a heritable disorder that we term adrenomyeloneuropathy; limited clinical information is available on a fifth case. All had adrenal insufficiency beginning in childhood and developed progressive spastic paraparesis in the third decade. Hypogonadism of variable severity was present in all four cases appropriately examined. Neurologic features included peripheral neuropathy, impotence, and sphincter disturbances. Late manifestations were cerebellar dysfunction in one case and dementia and hemiparesis in another. A family history of adrenal disease or spastic paraparesis was present in two cases and absent in one; in the other two, no family history was available. Although males are predominantly affected, the mode of inheritance is uncertain. Adrenomyeloneuropathy probably represents a clinically and genetically distinct variant of childhood adrenoleukodystrophy."}
{"id": "PMID:200862", "title": "Adrenomyeloneuropathy: a probable variant of adrenoleukodystrophy. II. General pathologic, neuropathologic, and biochemical aspects.", "content": "Histopathologic features were studied in postmortem examination of two men with adrenomyeloneuropathy, and biochemical studies were performed on one of these individuals. The histopathologic picture of one case included dying-back features in the nervous system and lamellar cytoplasmic inclusions in the brain, adrenal gland, and testis similar to those in adrenoleukodystrophy. Biochemical studies of the cerebral white matter of this individual revealed increased amounts of long-chain saturated fatty acids in cholesterol esters, an abnormality characteristic of adrenoleukodystrophy. Despite differences in clinical presentation and neuropathology, adrenomyeloneuropathy probably represents a distinct variant of adrenoleukodystrophy.", "contents": "Adrenomyeloneuropathy: a probable variant of adrenoleukodystrophy. II. General pathologic, neuropathologic, and biochemical aspects. Histopathologic features were studied in postmortem examination of two men with adrenomyeloneuropathy, and biochemical studies were performed on one of these individuals. The histopathologic picture of one case included dying-back features in the nervous system and lamellar cytoplasmic inclusions in the brain, adrenal gland, and testis similar to those in adrenoleukodystrophy. Biochemical studies of the cerebral white matter of this individual revealed increased amounts of long-chain saturated fatty acids in cholesterol esters, an abnormality characteristic of adrenoleukodystrophy. Despite differences in clinical presentation and neuropathology, adrenomyeloneuropathy probably represents a distinct variant of adrenoleukodystrophy."}
{"id": "PMID:200863", "title": "Cytomegalovirus complement fixation antibody in Guillain-Barr\u00e9 syndrome.", "content": "Cytomegalovirus, measles, and adenovirus antibodies were measured in the sera of 92 Guillain-Barr\u00e9 patients and 120 controls. Thirty patients (33 percent) had markedly elevated levels of complement-fixing antibody to cytomegalovirus and in 21, a fourfold or more alteration in titer was demonstrated. Diagnostic falls in titer were seen in most instances and no significant elevation to the other viral agents was found. The serologic findings reported here suggest that cytomegalovirus may be a common agent involved in the pathogenesis of the Guillain-Barr\u00e9 syndrome.", "contents": "Cytomegalovirus complement fixation antibody in Guillain-Barr\u00e9 syndrome. Cytomegalovirus, measles, and adenovirus antibodies were measured in the sera of 92 Guillain-Barr\u00e9 patients and 120 controls. Thirty patients (33 percent) had markedly elevated levels of complement-fixing antibody to cytomegalovirus and in 21, a fourfold or more alteration in titer was demonstrated. Diagnostic falls in titer were seen in most instances and no significant elevation to the other viral agents was found. The serologic findings reported here suggest that cytomegalovirus may be a common agent involved in the pathogenesis of the Guillain-Barr\u00e9 syndrome."}
{"id": "PMID:200866", "title": "[Radiological picture Turner's syndrome].", "content": "A review of the relevant literature is followed by presentation of the radiological picture, particularly that of the skeleton, in 8 patients with the clinical and endocrinological features and the chromosome pattern of Turner's syndrome. An indication is given of the weight to be attached to the main and lesser radiological signs, especially in cases where the absence of somatic features and detectable hypogonadism impede early diagnosis.", "contents": "[Radiological picture Turner's syndrome]. A review of the relevant literature is followed by presentation of the radiological picture, particularly that of the skeleton, in 8 patients with the clinical and endocrinological features and the chromosome pattern of Turner's syndrome. An indication is given of the weight to be attached to the main and lesser radiological signs, especially in cases where the absence of somatic features and detectable hypogonadism impede early diagnosis."}
{"id": "PMID:200876", "title": "Unexpected disseminated herpes simplex infection in a newborn.", "content": "Disseminated herpes simplex virus type 2 was unexpectedly discovered in a baby delivered by primary cesarean section at 36 weeks' gestation prior to rupture of the membranes. The mother was free of orogenital lesions at each prenatal examination. Examination of the placenta revealed chorioamnionitis implicating an ascending infection from the mother's infected genital tract.", "contents": "Unexpected disseminated herpes simplex infection in a newborn. Disseminated herpes simplex virus type 2 was unexpectedly discovered in a baby delivered by primary cesarean section at 36 weeks' gestation prior to rupture of the membranes. The mother was free of orogenital lesions at each prenatal examination. Examination of the placenta revealed chorioamnionitis implicating an ascending infection from the mother's infected genital tract."}
{"id": "PMID:200877", "title": "Clostridial myonecrosis of the postpartum uterus with radiologic diagnosis.", "content": "A case of clostridial uterine infection following prolonged labor and vaginal delivery is presented. Uterine myonecrosis with gas formation was diagnosed by radiologic studies. Antimicrobial therapy with megadosage penicillin was initiated and total abdominal hysterectomy performed. Three episodes of cardiac arrest occurred during surgery. Resuscitation was carried out with recovery.", "contents": "Clostridial myonecrosis of the postpartum uterus with radiologic diagnosis. A case of clostridial uterine infection following prolonged labor and vaginal delivery is presented. Uterine myonecrosis with gas formation was diagnosed by radiologic studies. Antimicrobial therapy with megadosage penicillin was initiated and total abdominal hysterectomy performed. Three episodes of cardiac arrest occurred during surgery. Resuscitation was carried out with recovery."}
{"id": "PMID:200878", "title": "Adenoid cystic carcinoma of the vulva. Malignant cylindroma.", "content": "A case of adenoid cystic carcinoma (cylindroma) of the vulva is presented, reviewing the clinical course and response to therapy over a 5-year period. Only 9 previous cases had been reported by 1963. Several sources of cell origin had been previously suggested. Findings and histology in this case support a relation to a similar tumor occurring in other sites of the upper respiratory tract and salivary gland.", "contents": "Adenoid cystic carcinoma of the vulva. Malignant cylindroma. A case of adenoid cystic carcinoma (cylindroma) of the vulva is presented, reviewing the clinical course and response to therapy over a 5-year period. Only 9 previous cases had been reported by 1963. Several sources of cell origin had been previously suggested. Findings and histology in this case support a relation to a similar tumor occurring in other sites of the upper respiratory tract and salivary gland."}
{"id": "PMID:200890", "title": "[Chloroquine neuromyopathy. One case in prophylactic maleriatherapy (author's transl)].", "content": "A case of neuromyopathy due to chronic chloroquine intoxication is reported. The neuromyopathy developped 9 months after malaria suppression therapy with chloroquine was started. The clinical picture was that of a peripherical neuropathy in the lower limbs and of a generalized myasthenic syndrome. Muscular biopsy showed typical pictures of \"vacuolar myopathy\". The metabolism of the drug was normal. The patient improved soon after chloroquine was discontinued.", "contents": "[Chloroquine neuromyopathy. One case in prophylactic maleriatherapy (author's transl)]. A case of neuromyopathy due to chronic chloroquine intoxication is reported. The neuromyopathy developped 9 months after malaria suppression therapy with chloroquine was started. The clinical picture was that of a peripherical neuropathy in the lower limbs and of a generalized myasthenic syndrome. Muscular biopsy showed typical pictures of \"vacuolar myopathy\". The metabolism of the drug was normal. The patient improved soon after chloroquine was discontinued."}
{"id": "PMID:200892", "title": "Compact form of SV40 viral minichromosome is resistant to nuclease: possible implications for chromatin structure.", "content": "We report two new findings bearing on the \"supranucleo-somal\" level of the structure of the Simian Virus 40 minichromosome. I) Isolated SV40 minichromosome which contains all five histones including HI/I/ exists in solution under approximately physiological ionic conditions as a compact roughly spherical particle approximately 300 A in diameter which is capable of fitting within the virus capsid. In spite of such a compact conformation of the minichromosome individual nucleosomes can be readily visualized within the particle. Compact state of SV40 minichromosome depends on both the presence of histone HI and maintenance of approximately physiological ionic strength of solution (micron approximately 0.15). Removal of HI results in a conversion of the compact minichromosomes into an extended (circular beaded) structure. 2) The compact form of the SV40 minichromosome in contract to its circular beaded form is virtually completely resistant to staphylococcal nuclease, strongly suggesting that in particular nuclease-sensitive parts of the internucleosomal DNA regions are not exposed on the outside of the compact SV40 minichromosome. On the other hand, DNase I which is known to attack both inter-and intranucleosomal DNA in the chronatin /2,3/ readily digests the compact form of the SV40 minichromosome. Possible models of the compact minichromosome and implications for higher order structures of the cellular chromatin are discussed.", "contents": "Compact form of SV40 viral minichromosome is resistant to nuclease: possible implications for chromatin structure. We report two new findings bearing on the \"supranucleo-somal\" level of the structure of the Simian Virus 40 minichromosome. I) Isolated SV40 minichromosome which contains all five histones including HI/I/ exists in solution under approximately physiological ionic conditions as a compact roughly spherical particle approximately 300 A in diameter which is capable of fitting within the virus capsid. In spite of such a compact conformation of the minichromosome individual nucleosomes can be readily visualized within the particle. Compact state of SV40 minichromosome depends on both the presence of histone HI and maintenance of approximately physiological ionic strength of solution (micron approximately 0.15). Removal of HI results in a conversion of the compact minichromosomes into an extended (circular beaded) structure. 2) The compact form of the SV40 minichromosome in contract to its circular beaded form is virtually completely resistant to staphylococcal nuclease, strongly suggesting that in particular nuclease-sensitive parts of the internucleosomal DNA regions are not exposed on the outside of the compact SV40 minichromosome. On the other hand, DNase I which is known to attack both inter-and intranucleosomal DNA in the chronatin /2,3/ readily digests the compact form of the SV40 minichromosome. Possible models of the compact minichromosome and implications for higher order structures of the cellular chromatin are discussed."}
{"id": "PMID:200893", "title": "Histone synthesis during infection of monkey kidney cells with Simian Virus 40.", "content": "The synthesis of histones during lytic infection of BSC-1 (African Green Monkey kidney) cells with SV40 has been investigated. The synthesis of all five classes of histones was stimulated, and all classes appeared to be stimulated to the same extent. The increase in rate of histone synthesis in response to SV40 infection was detectable several hours before SV40 DNA synthesis was measureable, and the rate of histone synthesis decreased at a time when SV40 DNA synthesis was occuring at a maximal or relatively high rate. In addition, the changes in rates of histone synthesis did not correlate well with the rates of host DNA synthesis during infection. Thus it appears that DNA synthesis and histone synthesis may not be strictly coupled in SV40 infected cells.", "contents": "Histone synthesis during infection of monkey kidney cells with Simian Virus 40. The synthesis of histones during lytic infection of BSC-1 (African Green Monkey kidney) cells with SV40 has been investigated. The synthesis of all five classes of histones was stimulated, and all classes appeared to be stimulated to the same extent. The increase in rate of histone synthesis in response to SV40 infection was detectable several hours before SV40 DNA synthesis was measureable, and the rate of histone synthesis decreased at a time when SV40 DNA synthesis was occuring at a maximal or relatively high rate. In addition, the changes in rates of histone synthesis did not correlate well with the rates of host DNA synthesis during infection. Thus it appears that DNA synthesis and histone synthesis may not be strictly coupled in SV40 infected cells."}
{"id": "PMID:200894", "title": "A rapid method for preparation of calf spleen exonuclease.", "content": "Chromatography on Concanavalin A sepharose is a simple procedure for partial purification of spleen phosphodiesterase. This procedure removes much, but not all, of the ribonuclease activity found as contaminant in most spleen phosphdisterase preparations.", "contents": "A rapid method for preparation of calf spleen exonuclease. Chromatography on Concanavalin A sepharose is a simple procedure for partial purification of spleen phosphodiesterase. This procedure removes much, but not all, of the ribonuclease activity found as contaminant in most spleen phosphdisterase preparations."}
{"id": "PMID:200900", "title": "Normal growth and development: current concepts.", "content": "Human growth and development are a continuum starting at conception. Prenatal growth can only be estimated at present but is an important consideration in an evaluation of a child's developmental status. Postnatal growth can be assessed for size attained (distance curve) or change over time (velocity curve). Velocity curves truly reflect the pattern of growth in stature.", "contents": "Normal growth and development: current concepts. Human growth and development are a continuum starting at conception. Prenatal growth can only be estimated at present but is an important consideration in an evaluation of a child's developmental status. Postnatal growth can be assessed for size attained (distance curve) or change over time (velocity curve). Velocity curves truly reflect the pattern of growth in stature."}
{"id": "PMID:200901", "title": "Granular cell myoblastoma of the biliary tree.", "content": "A granular cell myoblastoma of the common bile duct is described which caused episodes of jaundice in a young woman. Histological examination demonstrated a close association of the tumour with nerve fibres, tending to support the theory of origin from Schwann cells. The lesion is benign and after excision carries an excellent prognosis.", "contents": "Granular cell myoblastoma of the biliary tree. A granular cell myoblastoma of the common bile duct is described which caused episodes of jaundice in a young woman. Histological examination demonstrated a close association of the tumour with nerve fibres, tending to support the theory of origin from Schwann cells. The lesion is benign and after excision carries an excellent prognosis."}
{"id": "PMID:200905", "title": "Cellular transformation and differentiation. Effect of Rous sarcoma virus transformation on sulfated proteoglycan synthesis by chicken chondrocytes.", "content": "Incorporation of sulfate into sulfated proteoglycans by isolated chicken chondrocytes was inhibited up to 74% by transformation with the Rous sarcoma virus, and a similar inhibitory effect was observed on acetate incorporation into chondroitin sulfate. Slower sedimenting sulfated proteoglycans appear after the viral transformation. The ratio of chondroitin 4-sulfate to chondroitin 6-sulfate in these slower sedimenting sulfated proteoglycans was different from that of normal chondrocytes, but the chain lengths of sulfated glycosaminoglycans produced by normal chondrocytes and transformed chondrocytes were not significantly different. Chondrocytes were also infected with a temperature-sensitive mutant of RSV, ts LA24, which has a temperature-sensitive lesion in the transforming gene. Hyaluronic acid production by these cells was increased, and the slower sedimenting sulfated proteoglycan was produced only at the permissive temperature.", "contents": "Cellular transformation and differentiation. Effect of Rous sarcoma virus transformation on sulfated proteoglycan synthesis by chicken chondrocytes. Incorporation of sulfate into sulfated proteoglycans by isolated chicken chondrocytes was inhibited up to 74% by transformation with the Rous sarcoma virus, and a similar inhibitory effect was observed on acetate incorporation into chondroitin sulfate. Slower sedimenting sulfated proteoglycans appear after the viral transformation. The ratio of chondroitin 4-sulfate to chondroitin 6-sulfate in these slower sedimenting sulfated proteoglycans was different from that of normal chondrocytes, but the chain lengths of sulfated glycosaminoglycans produced by normal chondrocytes and transformed chondrocytes were not significantly different. Chondrocytes were also infected with a temperature-sensitive mutant of RSV, ts LA24, which has a temperature-sensitive lesion in the transforming gene. Hyaluronic acid production by these cells was increased, and the slower sedimenting sulfated proteoglycan was produced only at the permissive temperature."}
{"id": "PMID:200906", "title": "Location of protein(s) involved in oligomycin-induced inhibition of mitochondrial adenosinetriphosphatase near the outer surface of the inner membrane.", "content": "Mitoplasts, that is, mitochondria freed from their outer membranes, were prepared from pig heart. Sonication induced an inversion of these mitoplasts, giving inside-out vesicles. Added cytochrome c can be bound much better to mitoplasts than to sonicated vesicles; addition of trypsin increased adenosinetriphosphatase (ATPase) (ATP phosphohydrolase; EC 3.6.1.3) activity of sonicated vesicles without significantly affecting that of the mitoplasts. Since the site of fixation of cytochrome c was located on the outer side of the inner mitochondrial membrane and since the protein inhibitor of the mitochondrial ATPase is present on the inner face of the inner membrane and is very sensitive to trypsin, it can be concluded that mitoplasts are mainly oriented as normal mitochondria while sonicated vesicles are mainly inverted. Trypsin treatment can abolish the oligomycin sensitivity of ATPase activity of either mitoplasts or sonicated vesicles. However, trypsin induced the solubilization of the soluble F(1)-ATPase of sonicated vesicles while the ATPase activity remained with the mitoplasts after trypsin action. Therefore, trypsin destroyed the oligomycin effect by rupturing the liaison between F(1) and the membrane in sonicated vesicles. On the other hand, the effect of trypsin on mitoplasts must be attributed to the hydrolysis of a protein located near the outer surface of the inner membrane that is at least structurally involved in the oligomycin sensitivity of the ATPase complex.", "contents": "Location of protein(s) involved in oligomycin-induced inhibition of mitochondrial adenosinetriphosphatase near the outer surface of the inner membrane. Mitoplasts, that is, mitochondria freed from their outer membranes, were prepared from pig heart. Sonication induced an inversion of these mitoplasts, giving inside-out vesicles. Added cytochrome c can be bound much better to mitoplasts than to sonicated vesicles; addition of trypsin increased adenosinetriphosphatase (ATPase) (ATP phosphohydrolase; EC 3.6.1.3) activity of sonicated vesicles without significantly affecting that of the mitoplasts. Since the site of fixation of cytochrome c was located on the outer side of the inner mitochondrial membrane and since the protein inhibitor of the mitochondrial ATPase is present on the inner face of the inner membrane and is very sensitive to trypsin, it can be concluded that mitoplasts are mainly oriented as normal mitochondria while sonicated vesicles are mainly inverted. Trypsin treatment can abolish the oligomycin sensitivity of ATPase activity of either mitoplasts or sonicated vesicles. However, trypsin induced the solubilization of the soluble F(1)-ATPase of sonicated vesicles while the ATPase activity remained with the mitoplasts after trypsin action. Therefore, trypsin destroyed the oligomycin effect by rupturing the liaison between F(1) and the membrane in sonicated vesicles. On the other hand, the effect of trypsin on mitoplasts must be attributed to the hydrolysis of a protein located near the outer surface of the inner membrane that is at least structurally involved in the oligomycin sensitivity of the ATPase complex."}
{"id": "PMID:200903", "title": "[Mechanism of stimulation of protein synthesis in the thyroid gland with cyclic nucleotides].", "content": "A study was made of cyclic guanosine-3+, 5+-monophosphate (cGMP) on protein synthesis in the cell-free system of the thyroid gland. Preincubation of S30 fraction with cGMP led to increase of labeled amino acid incorporation into proteins (by 56% with the cGMP concentration of 1.73 X 10(-5) M, and by 160% with the concentration of 2 X 10(-4)). No stimulating effect was observed on addition of cGMP directly into the incubation medium. The results obtained suggested that protein synthesis was stimulated under the effect of cGMP at the translation level. The same protein fractions [27S, 19S, 12S, 3-8S (I) and 3-8S (II)] were revealed by disc-electrophoresis of soluble proteins synthesized in the cell-free system in which polyribosomes preincubated with cAMP (1.73 X 10(-5) M) were used as in the system devoid of cAMP. Specific radioactivity of thyroglobulin subunits corresponded in experiments with cAMP to that in experiments without cAMP. At the same time specific radioactivity of 19S thyroglobulin was more than doubled. It can be supposed that thyroglobulin subunit synthesis was accelerated under the effect of cAMP, and, as a result, labeled thyroglobulin increased in the system. The data obtained confirmed a hypothesis put forward earlier that cAMP had a direct influence upon the translation process.", "contents": "[Mechanism of stimulation of protein synthesis in the thyroid gland with cyclic nucleotides]. A study was made of cyclic guanosine-3+, 5+-monophosphate (cGMP) on protein synthesis in the cell-free system of the thyroid gland. Preincubation of S30 fraction with cGMP led to increase of labeled amino acid incorporation into proteins (by 56% with the cGMP concentration of 1.73 X 10(-5) M, and by 160% with the concentration of 2 X 10(-4)). No stimulating effect was observed on addition of cGMP directly into the incubation medium. The results obtained suggested that protein synthesis was stimulated under the effect of cGMP at the translation level. The same protein fractions [27S, 19S, 12S, 3-8S (I) and 3-8S (II)] were revealed by disc-electrophoresis of soluble proteins synthesized in the cell-free system in which polyribosomes preincubated with cAMP (1.73 X 10(-5) M) were used as in the system devoid of cAMP. Specific radioactivity of thyroglobulin subunits corresponded in experiments with cAMP to that in experiments without cAMP. At the same time specific radioactivity of 19S thyroglobulin was more than doubled. It can be supposed that thyroglobulin subunit synthesis was accelerated under the effect of cAMP, and, as a result, labeled thyroglobulin increased in the system. The data obtained confirmed a hypothesis put forward earlier that cAMP had a direct influence upon the translation process."}
{"id": "PMID:200907", "title": "Elimination of size and charge heterogeneities of human leukocyte interferons by chemical cleavage.", "content": "Human leukocyte interferon (HuLeIF) preparations contain distinct molecular forms of interferon exhibiting significant heterogeneties in sizes when analyzed by electrophoresis in sodium dodecyl sulfate (NaDodSO(4))/polyacrylamide gels, migrating in two broad bands of activity with peaks at about 21,000 and 15,000 daltons. HuLeIFs exhibit extensive charge heterogeneities when analyzed by isoelectric focusing, resolving into several major peaks of approximately equal activity distributed from pH 5.7 to 7.0. When HuLeIF preparations are treated with 0.01 M sodium periodate buffer, pH 4.5, at 4 degrees , both the size and charge heterogeneities rapidly disappear: periodate-treated HuLeIF migrates as a single, narrow band at 15,000 daltons in NaDodSO(4)/polyacrylamide gels and focuses as a single, narrow band at pH 5.7. Quantitative considerations suggest that either the larger, heterogeneously charged HuLeIFs are converted to the smaller, size- and charge-homogeneous interferon by extensive chemical deglycosylation, or, alternatively, the smaller, 15,000 dalton, pH 5.7 interferon is much more stable to periodate treatment than are the other interferon forms. However, the activity of each of the variously charged forms of HuLeIF isolated from focusing gels exhibited the same stability as the pH 5.7 component; similarly, the activity of each of the size-forms of HuLeIF isolated from NaDodSO(4)/polyacrylamide gels exhibited the same stability as the 15,000-dalton interferon.", "contents": "Elimination of size and charge heterogeneities of human leukocyte interferons by chemical cleavage. Human leukocyte interferon (HuLeIF) preparations contain distinct molecular forms of interferon exhibiting significant heterogeneties in sizes when analyzed by electrophoresis in sodium dodecyl sulfate (NaDodSO(4))/polyacrylamide gels, migrating in two broad bands of activity with peaks at about 21,000 and 15,000 daltons. HuLeIFs exhibit extensive charge heterogeneities when analyzed by isoelectric focusing, resolving into several major peaks of approximately equal activity distributed from pH 5.7 to 7.0. When HuLeIF preparations are treated with 0.01 M sodium periodate buffer, pH 4.5, at 4 degrees , both the size and charge heterogeneities rapidly disappear: periodate-treated HuLeIF migrates as a single, narrow band at 15,000 daltons in NaDodSO(4)/polyacrylamide gels and focuses as a single, narrow band at pH 5.7. Quantitative considerations suggest that either the larger, heterogeneously charged HuLeIFs are converted to the smaller, size- and charge-homogeneous interferon by extensive chemical deglycosylation, or, alternatively, the smaller, 15,000 dalton, pH 5.7 interferon is much more stable to periodate treatment than are the other interferon forms. However, the activity of each of the variously charged forms of HuLeIF isolated from focusing gels exhibited the same stability as the pH 5.7 component; similarly, the activity of each of the size-forms of HuLeIF isolated from NaDodSO(4)/polyacrylamide gels exhibited the same stability as the 15,000-dalton interferon."}
{"id": "PMID:200908", "title": "Acyl group and electron pair relay system: a network of interacting lipoyl moieties in the pyruvate and alpha-ketoglutarate dehydrogenase complexes from Escherichia coli.", "content": "The dihydrolipoyl transacetylase component of the Escherichia coli pyruvate dehydrogenase complex [pyruvate:lipoate oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1] bears two sites on each of its 24 polypeptide chains that undergo reductive acetylation by [2-(14)C]pyruvate and thiamin pyrophosphate, acetylation by [1-(14)C]acetyl-CoA in the presence of DPNH, and reaction with N-ethyl[2,3-(14)C]maleimide in the presence of pyruvate and thiamin pyrophosphate. The data strongly imply that these sites are covalently bound lipoyl moieties. The results of similar experiments with the E. coli alpha-ketoglutarate dehydrogenase complex [2-oxoglutarate:lipoate oxidoreductase (decarboxylating and acceptor-succinylating), EC 1.2.4.2] indicate that its dihydrolipoyl transsuccinylase component bears only one lipoyl moiety on each of its 24 chains. Charging of the 48 acetyl acceptor sites on the transacetylase or the 24 succinyl acceptor sites on the transsuccinylase by pyruvate or alpha-ketoglutarate, respectively, and thiamin pyrophosphate was observed in the presence of only a few functionally active pyruvate dehydrogenase or alpha-ketoglutarate dehydrogenase chains. Extensive crosslinking of the transacetylase chains was observed when the pyruvate dehydrogenase complex was treated with pyruvate and thiamin pyrophosphate or with DPNH in the presence of N,N'-o- or N,N'-p-phenylenedimaleimide, respectively. When the alpha-ketoglutarate dehydrogenase complex was treated with DPNH in the presence of N,N'-p-phenylenedimaleimide, only transsuccinylase monomers and crosslinked transsuccinylase dimers were detected. It appears that the 48 lipoyl moieties in the transacetylase and the 24 lipoyl moieties in the transsuccinylase comprise an interacting network that functions as an acyl group and electron pair relay system through thiol-disulfide and acyl-transfer reactions among all of the lipoyl moieties.", "contents": "Acyl group and electron pair relay system: a network of interacting lipoyl moieties in the pyruvate and alpha-ketoglutarate dehydrogenase complexes from Escherichia coli. The dihydrolipoyl transacetylase component of the Escherichia coli pyruvate dehydrogenase complex [pyruvate:lipoate oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1] bears two sites on each of its 24 polypeptide chains that undergo reductive acetylation by [2-(14)C]pyruvate and thiamin pyrophosphate, acetylation by [1-(14)C]acetyl-CoA in the presence of DPNH, and reaction with N-ethyl[2,3-(14)C]maleimide in the presence of pyruvate and thiamin pyrophosphate. The data strongly imply that these sites are covalently bound lipoyl moieties. The results of similar experiments with the E. coli alpha-ketoglutarate dehydrogenase complex [2-oxoglutarate:lipoate oxidoreductase (decarboxylating and acceptor-succinylating), EC 1.2.4.2] indicate that its dihydrolipoyl transsuccinylase component bears only one lipoyl moiety on each of its 24 chains. Charging of the 48 acetyl acceptor sites on the transacetylase or the 24 succinyl acceptor sites on the transsuccinylase by pyruvate or alpha-ketoglutarate, respectively, and thiamin pyrophosphate was observed in the presence of only a few functionally active pyruvate dehydrogenase or alpha-ketoglutarate dehydrogenase chains. Extensive crosslinking of the transacetylase chains was observed when the pyruvate dehydrogenase complex was treated with pyruvate and thiamin pyrophosphate or with DPNH in the presence of N,N'-o- or N,N'-p-phenylenedimaleimide, respectively. When the alpha-ketoglutarate dehydrogenase complex was treated with DPNH in the presence of N,N'-p-phenylenedimaleimide, only transsuccinylase monomers and crosslinked transsuccinylase dimers were detected. It appears that the 48 lipoyl moieties in the transacetylase and the 24 lipoyl moieties in the transsuccinylase comprise an interacting network that functions as an acyl group and electron pair relay system through thiol-disulfide and acyl-transfer reactions among all of the lipoyl moieties."}
{"id": "PMID:200909", "title": "A light-activated GTPase in vertebrate photoreceptors: regulation of light-activated cyclic GMP phosphodiesterase.", "content": "We have been studying the mechanism by which light and nucleoside triphosphates activate the discmembrane phosphodiesterase (oligonucleate 5'-nucleotidohydrolase; EC 3.1.4.1) in frog rod outer segments. GTP is orders of magnitude more effective than ATP as a cofactor in the light-dependent activation step. GTP and the analogue guanylyl-imidodiphosphate function equally as allosteric activators of photoreceptor phosphodiesterase rather than participating in the formation of a phosphorylated activator. Moreover, we have found a light-activated (5-fold) GTPase which participates in the modulation of photoreceptor phosphodiesterase. This GTPase activity appears necessary for the reversal of phosphodiesterase activation in vitro and may play a critical role in the in vivo regulation of light-sensitive phosphodiesterase. The K(m) for GTP in the light-activated GTPase reaction is <1 muM. The light sensitivity of this GTPase (number of photons required for half-maximal activation) is identical to that of light-activated phosphodiesterase. The GTPase action spectrum corresponds to the absorption spectrum of rhodopsin. There is, in addition, a light-insensitive GTPase activity with a K(m) for GTP of 90 muM. At GTP concentrations above 5 muM, there is no appreciable activation of GTPase activity by light. The substrate K(m) values for guanylate cyclase, light-activated GTPase, and light-activated phosphodiesterase order an enzyme array that might permit light to simultaneously cause the hydrolysis of both the substrate and product of guanylate cyclase. These findings reveal yet another facet of light regulation of photoreceptor/cyclic GMP levels and also provide a striking analogy to the GTP regulation of nonphotoreceptor, hormone-sensitive adenylate cyclase.", "contents": "A light-activated GTPase in vertebrate photoreceptors: regulation of light-activated cyclic GMP phosphodiesterase. We have been studying the mechanism by which light and nucleoside triphosphates activate the discmembrane phosphodiesterase (oligonucleate 5'-nucleotidohydrolase; EC 3.1.4.1) in frog rod outer segments. GTP is orders of magnitude more effective than ATP as a cofactor in the light-dependent activation step. GTP and the analogue guanylyl-imidodiphosphate function equally as allosteric activators of photoreceptor phosphodiesterase rather than participating in the formation of a phosphorylated activator. Moreover, we have found a light-activated (5-fold) GTPase which participates in the modulation of photoreceptor phosphodiesterase. This GTPase activity appears necessary for the reversal of phosphodiesterase activation in vitro and may play a critical role in the in vivo regulation of light-sensitive phosphodiesterase. The K(m) for GTP in the light-activated GTPase reaction is <1 muM. The light sensitivity of this GTPase (number of photons required for half-maximal activation) is identical to that of light-activated phosphodiesterase. The GTPase action spectrum corresponds to the absorption spectrum of rhodopsin. There is, in addition, a light-insensitive GTPase activity with a K(m) for GTP of 90 muM. At GTP concentrations above 5 muM, there is no appreciable activation of GTPase activity by light. The substrate K(m) values for guanylate cyclase, light-activated GTPase, and light-activated phosphodiesterase order an enzyme array that might permit light to simultaneously cause the hydrolysis of both the substrate and product of guanylate cyclase. These findings reveal yet another facet of light regulation of photoreceptor/cyclic GMP levels and also provide a striking analogy to the GTP regulation of nonphotoreceptor, hormone-sensitive adenylate cyclase."}
{"id": "PMID:200910", "title": "Semisynthetic cytochrome c.", "content": "Horse heart cytochrome c can be split with cyanogen bromide into a heme peptide (residues 1-65) and a nonheme peptide (residues 66-104). In a process involving (i) complex formation between the two fragments and (ii) restoration of the severed peptide linkage, a fully active cytochrome c preparation can be re-formed. Use has been made of this process to couple the heme peptide to peptide 66-104 synthesized by the Merrifield solid-phase procedure. The semisynthetic product formed in this manner is indistinguishable from reconstituted cytochrome c prepared with nonsynthetic peptide 66-104.", "contents": "Semisynthetic cytochrome c. Horse heart cytochrome c can be split with cyanogen bromide into a heme peptide (residues 1-65) and a nonheme peptide (residues 66-104). In a process involving (i) complex formation between the two fragments and (ii) restoration of the severed peptide linkage, a fully active cytochrome c preparation can be re-formed. Use has been made of this process to couple the heme peptide to peptide 66-104 synthesized by the Merrifield solid-phase procedure. The semisynthetic product formed in this manner is indistinguishable from reconstituted cytochrome c prepared with nonsynthetic peptide 66-104."}
{"id": "PMID:200911", "title": "Studies on the mechanism of phosphorylation of synthetic polypeptides by a calf thymus cyclic AMP-dependent protein kinase.", "content": "Synthetic polypeptides were employed as substrates in kinetic analyses of the reaction mechanism for the catalytic subunit of a cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) from calf thymus. This enzyme preparation was shown to catalyze the transfer of phosphate from ATP to histone H1 from calf thymus, as well as to two synthetic polypeptides, Arg-Lys-Ala-Ser-Gly-Pro (H1-6) and Arg-Arg-Lys-Ala-Ser-Gly-Pro (H1-7), corresponding to the amino acid sequence about serine-38 in calf H1. A related, basic heptapeptide corresponding to a sequence from pig liver pyruvate kinase, Leu-Arg-Arg-Ala-Ser-Leu-Gly (K), was also a substrate. The stoichiometry of peptide phosphorylation was established in each case as the transfer of 1 mol of phosphate from the gamma position of MgATP to the serine hydroxyl of 1 mol of the peptide. Steady-state, initial-velocity, kinetic parameters were determined for each substrate, using various concentrations of ATP. Under the conditions used, all synthetic peptides reacted with greater maximum velocities than whole histone H1. Nevertheless, the K(m) for H1, 54 muM, was lower than the K(m) values of the synthetic substrates. The most efficient substrate was peptide K, which had a V(max) of 50.6 mumol/min per mg of kinase and a K(m) of 63 muM. In the absence of peptide substrate no ATPase activity was detectable at a sensitivity of 0.05% of the rate of peptide phosphorylation, suggesting that ATP is not cleaved to form an unstable phosphoenzyme complex. The data are consistent with a sequential reaction mechanism involving a ternary complex between enzyme, polypeptide substrate, and ATP.", "contents": "Studies on the mechanism of phosphorylation of synthetic polypeptides by a calf thymus cyclic AMP-dependent protein kinase. Synthetic polypeptides were employed as substrates in kinetic analyses of the reaction mechanism for the catalytic subunit of a cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) from calf thymus. This enzyme preparation was shown to catalyze the transfer of phosphate from ATP to histone H1 from calf thymus, as well as to two synthetic polypeptides, Arg-Lys-Ala-Ser-Gly-Pro (H1-6) and Arg-Arg-Lys-Ala-Ser-Gly-Pro (H1-7), corresponding to the amino acid sequence about serine-38 in calf H1. A related, basic heptapeptide corresponding to a sequence from pig liver pyruvate kinase, Leu-Arg-Arg-Ala-Ser-Leu-Gly (K), was also a substrate. The stoichiometry of peptide phosphorylation was established in each case as the transfer of 1 mol of phosphate from the gamma position of MgATP to the serine hydroxyl of 1 mol of the peptide. Steady-state, initial-velocity, kinetic parameters were determined for each substrate, using various concentrations of ATP. Under the conditions used, all synthetic peptides reacted with greater maximum velocities than whole histone H1. Nevertheless, the K(m) for H1, 54 muM, was lower than the K(m) values of the synthetic substrates. The most efficient substrate was peptide K, which had a V(max) of 50.6 mumol/min per mg of kinase and a K(m) of 63 muM. In the absence of peptide substrate no ATPase activity was detectable at a sensitivity of 0.05% of the rate of peptide phosphorylation, suggesting that ATP is not cleaved to form an unstable phosphoenzyme complex. The data are consistent with a sequential reaction mechanism involving a ternary complex between enzyme, polypeptide substrate, and ATP."}
{"id": "PMID:200912", "title": "Integration of avian sarcoma virus DNA sequences in transformed mammalian cells.", "content": "DNA from six avian sarcoma virus (ASV)-transformed mammalian cell lines was digested with the restriction endonucleases EcoRI, Xho I, or Sal I, fractionated by agarose gel electrophoresis, transferred to nitrocellulose filter strips, and hybridized with specific ASV [32P]cDNA probes. DNA from all of the ASV-transformed cell lines yielded three common virus-specific DNA fragments (2.4, 1.8, and 1.3 X 10(6) daltons) upon cleavage with EcoRI. Xho I appeared to cleave at least once within the integrated provirus and yielded a common fragment of 3.3 X 10(6) daltons as well as a second virus-specific DNA fragment whose size varied from 4.0 to 5.0 X 10(6) daltons in the different transformed cell lines. Sal I did not cleave within the provirus and yielded a single major virus-specific fragment of about 11 X 10(6) daltons in all transformed lines examined. Using specific cDNA probes, we show that the 1.8 X 10(6)-dalton EcoRI fragment contains sequences homologous to the 3' end of the viral RNA as well as to the src region of the viral genome. These studies clearly demonstrate that the same region on the ASV genome is utilized for provirus integration in different ASV-transformed cell lines.", "contents": "Integration of avian sarcoma virus DNA sequences in transformed mammalian cells. DNA from six avian sarcoma virus (ASV)-transformed mammalian cell lines was digested with the restriction endonucleases EcoRI, Xho I, or Sal I, fractionated by agarose gel electrophoresis, transferred to nitrocellulose filter strips, and hybridized with specific ASV [32P]cDNA probes. DNA from all of the ASV-transformed cell lines yielded three common virus-specific DNA fragments (2.4, 1.8, and 1.3 X 10(6) daltons) upon cleavage with EcoRI. Xho I appeared to cleave at least once within the integrated provirus and yielded a common fragment of 3.3 X 10(6) daltons as well as a second virus-specific DNA fragment whose size varied from 4.0 to 5.0 X 10(6) daltons in the different transformed cell lines. Sal I did not cleave within the provirus and yielded a single major virus-specific fragment of about 11 X 10(6) daltons in all transformed lines examined. Using specific cDNA probes, we show that the 1.8 X 10(6)-dalton EcoRI fragment contains sequences homologous to the 3' end of the viral RNA as well as to the src region of the viral genome. These studies clearly demonstrate that the same region on the ASV genome is utilized for provirus integration in different ASV-transformed cell lines."}
{"id": "PMID:200913", "title": "The RNA of avian acute leukemia virus MC29.", "content": "The RNA of myelocytoma virus MC29, a replication-defective avian acute leukemia virus, was investigated. Sedimentation and electrophoretic analyses indicated that the virus contains a distinct 28S RNA with about 5700 nucleotides. It is the smallest avian tumor virus RNA detected to date. The small size of the RNA suggests that the defectiveness of the virus is due to deletions in replicative genes. The RNA shared 3 to 5 of 30 large RNase T1-resistant oligonucleotides with the RNA of other avian leukosis and sarcoma and may represent the transforming information of the virus. Sequences of the conserved transforming gene of avian sarcoma viruses were not detected in MC29 RNA. It was concluded that the transforming sequences of MC29 RNA define a new class of avian tumor viral transforming genes.", "contents": "The RNA of avian acute leukemia virus MC29. The RNA of myelocytoma virus MC29, a replication-defective avian acute leukemia virus, was investigated. Sedimentation and electrophoretic analyses indicated that the virus contains a distinct 28S RNA with about 5700 nucleotides. It is the smallest avian tumor virus RNA detected to date. The small size of the RNA suggests that the defectiveness of the virus is due to deletions in replicative genes. The RNA shared 3 to 5 of 30 large RNase T1-resistant oligonucleotides with the RNA of other avian leukosis and sarcoma and may represent the transforming information of the virus. Sequences of the conserved transforming gene of avian sarcoma viruses were not detected in MC29 RNA. It was concluded that the transforming sequences of MC29 RNA define a new class of avian tumor viral transforming genes."}
{"id": "PMID:200914", "title": "Steroidogenic activity of fragments of adrenocorticotropin with arginine in residue positions 3 and 5.", "content": "The maximal steroidogenic response (Smax) to adrenocorticotropin (ACTH) is enhanced by the substitution of arginine in position 3. Though the Smax of adrenocorticotropin-(3-10)-octapeptide [ACTH-(3-10)] is only 20% of ACTH-(1-24) in isolated rabbit adrenal cells and 10% in rat cells, [Arg3]ACTH-(3-10) has an Smax comparable to that of the longer peptide. Activity determined from the midpoints of dose-response curves (A50), however, is several orders of magnitude less. The Smax of ACTH-(4-10) is not significantly different from that of the 3-10 analog. Substitution of arginine in the 5 position of ACTH-(4-10) decreases activity for rabbit cells, but does not affect activity for rat cells. The substitution of arginine in the 5 position of ACTH-(1-20) markedly decreases Smax in rabbit but not rat cells. The Smax of [Arg 3,5)]ACTH-(3-10), containing both substitutions, is greater than that of ACTH-(3-10), but much less than that of [Arg3]acth-(3-10) in both species studied. These findings contrast with those in the rabbit adipocyte, where both arginine-containing ACTH analogs have enhanced activity and the effects of both substitutions in a single peptide are additive.", "contents": "Steroidogenic activity of fragments of adrenocorticotropin with arginine in residue positions 3 and 5. The maximal steroidogenic response (Smax) to adrenocorticotropin (ACTH) is enhanced by the substitution of arginine in position 3. Though the Smax of adrenocorticotropin-(3-10)-octapeptide [ACTH-(3-10)] is only 20% of ACTH-(1-24) in isolated rabbit adrenal cells and 10% in rat cells, [Arg3]ACTH-(3-10) has an Smax comparable to that of the longer peptide. Activity determined from the midpoints of dose-response curves (A50), however, is several orders of magnitude less. The Smax of ACTH-(4-10) is not significantly different from that of the 3-10 analog. Substitution of arginine in the 5 position of ACTH-(4-10) decreases activity for rabbit cells, but does not affect activity for rat cells. The substitution of arginine in the 5 position of ACTH-(1-20) markedly decreases Smax in rabbit but not rat cells. The Smax of [Arg 3,5)]ACTH-(3-10), containing both substitutions, is greater than that of ACTH-(3-10), but much less than that of [Arg3]acth-(3-10) in both species studied. These findings contrast with those in the rabbit adipocyte, where both arginine-containing ACTH analogs have enhanced activity and the effects of both substitutions in a single peptide are additive."}
{"id": "PMID:200915", "title": "Replication of viral RNA by a defective interfering vesicular stomatitis virus particle in the absence of helper virus.", "content": "The genome of a defective interfering particle (DILT) derived from the heat-resistant strain of vesicular stomatitis virus is expressed in vivo without the assistance of infectious helper virus. The rates of RNA synthesis in the presence of cycloheximide (primary transcription) are the same when infections are with equal numbers of physical particles of DILT or virus. With this treatment, DILT synthesizes only 12-17S mRNAs as characterized by size, polarity, and polyadenylylation. In the absence of cycloheximide, DILT-infected cells produce not only these mRNAs but also a 28S RNA species. This RNA, which represents one half of the viral specific RNA, contains newly synthesized full-length (+) and (-) strand DILT RNA. Both strands are found intracellularly as ribonucleoprotein complexes. Without cycloheximide present, the rate of RNA synthesis by DILT was less than that by virus. This curtailment is most likely due to the inability of DILT to synthesize L protein mRNA. An expanded role for defective interfering particles in infection is discussed.", "contents": "Replication of viral RNA by a defective interfering vesicular stomatitis virus particle in the absence of helper virus. The genome of a defective interfering particle (DILT) derived from the heat-resistant strain of vesicular stomatitis virus is expressed in vivo without the assistance of infectious helper virus. The rates of RNA synthesis in the presence of cycloheximide (primary transcription) are the same when infections are with equal numbers of physical particles of DILT or virus. With this treatment, DILT synthesizes only 12-17S mRNAs as characterized by size, polarity, and polyadenylylation. In the absence of cycloheximide, DILT-infected cells produce not only these mRNAs but also a 28S RNA species. This RNA, which represents one half of the viral specific RNA, contains newly synthesized full-length (+) and (-) strand DILT RNA. Both strands are found intracellularly as ribonucleoprotein complexes. Without cycloheximide present, the rate of RNA synthesis by DILT was less than that by virus. This curtailment is most likely due to the inability of DILT to synthesize L protein mRNA. An expanded role for defective interfering particles in infection is discussed."}
{"id": "PMID:200916", "title": "Choleragen activation of solubilized adenylate cyclase: requirement for GTP and protein activator for demonstration of enzymatic activity.", "content": "The requirements for choleragen activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] were investigated by using an enzyme preparation solubilized with Triton X-100 from an extensively washed brain particulate fraction and partially purified with DEAE-cellulose. Unlike the particulate enzyme, this preparation was not activated after incubation with choleragen plus dithiothreitol, ATP, and NAD. Addition of the purified protein activator of cyclic nucleotide phosphodiesterase and calcium to the partially purified enzyme increased basal activity somewhat, but choleragen activation was minimal. When cyclase was incubated with GTP plus the protein activator (and calcium), choleragen markedly increased the activity 3- to 6-fold. When GppNHp and protein activator were incubated with the cyclase prior to assay, activity was elevated but no effect of choleragen was observed. GTP and GppNHp had relatively small effects on cyclase activity in the absence of protein activator or if they were added directly to the assay. Boiled brain supernatant was consistently more effective than protein activator (plus calcium) and GTP, suggesting that other factors are required for maximal cyclase activity after choleragen treatment. It appears that the cyclase system is dissociable into several components, all of which may be necessary for optimal regulation of activity. It is probable that one of these is the heat-stable calcium-dependent protein activator of cyclic nucleotide phosphodiesterase and adenylate cyclase that we have found is required along with GTP for demonstration of choleragen activation of partially purified brain adenylate cyclase.", "contents": "Choleragen activation of solubilized adenylate cyclase: requirement for GTP and protein activator for demonstration of enzymatic activity. The requirements for choleragen activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] were investigated by using an enzyme preparation solubilized with Triton X-100 from an extensively washed brain particulate fraction and partially purified with DEAE-cellulose. Unlike the particulate enzyme, this preparation was not activated after incubation with choleragen plus dithiothreitol, ATP, and NAD. Addition of the purified protein activator of cyclic nucleotide phosphodiesterase and calcium to the partially purified enzyme increased basal activity somewhat, but choleragen activation was minimal. When cyclase was incubated with GTP plus the protein activator (and calcium), choleragen markedly increased the activity 3- to 6-fold. When GppNHp and protein activator were incubated with the cyclase prior to assay, activity was elevated but no effect of choleragen was observed. GTP and GppNHp had relatively small effects on cyclase activity in the absence of protein activator or if they were added directly to the assay. Boiled brain supernatant was consistently more effective than protein activator (plus calcium) and GTP, suggesting that other factors are required for maximal cyclase activity after choleragen treatment. It appears that the cyclase system is dissociable into several components, all of which may be necessary for optimal regulation of activity. It is probable that one of these is the heat-stable calcium-dependent protein activator of cyclic nucleotide phosphodiesterase and adenylate cyclase that we have found is required along with GTP for demonstration of choleragen activation of partially purified brain adenylate cyclase."}
{"id": "PMID:200917", "title": "Homology between a prolyl hydroxylase subunit and a tissue protein that crossreacts immunologically with the enzyme.", "content": "A protein, enzymatically inactive but immunologically related to prolyl hydroxylase (prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase; EC 1.14.11.2) (cross-reacting protein), has been purified to near homogeneity from skin of newborn rats. The purified protein has a molecular weight of 60,000 on gel filtration and sodium dodecyl sulfate gel electrophoresis, corresponding to that of the smaller of the two dissimilar subunits of the enzyme. The two subunits of prolyl hydroxylase differ markedly from one another in their amino acid compositions, but crossreating protein and the smaller subunit are very similar in composition. On antibody-affinity chromatography both subunits reacted with the antibody developed against the intact enzyme. Neither crossreacting protein nor the 60,000 molecular weight subunit was adsorbed onto concanavalin A, which adsorbed the intact enzyme as well as the larger subunit. It would appear that crossreacting protein is identical to one of the subunits of prolyl hydroxylase or metabolically related to it.", "contents": "Homology between a prolyl hydroxylase subunit and a tissue protein that crossreacts immunologically with the enzyme. A protein, enzymatically inactive but immunologically related to prolyl hydroxylase (prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase; EC 1.14.11.2) (cross-reacting protein), has been purified to near homogeneity from skin of newborn rats. The purified protein has a molecular weight of 60,000 on gel filtration and sodium dodecyl sulfate gel electrophoresis, corresponding to that of the smaller of the two dissimilar subunits of the enzyme. The two subunits of prolyl hydroxylase differ markedly from one another in their amino acid compositions, but crossreating protein and the smaller subunit are very similar in composition. On antibody-affinity chromatography both subunits reacted with the antibody developed against the intact enzyme. Neither crossreacting protein nor the 60,000 molecular weight subunit was adsorbed onto concanavalin A, which adsorbed the intact enzyme as well as the larger subunit. It would appear that crossreacting protein is identical to one of the subunits of prolyl hydroxylase or metabolically related to it."}
{"id": "PMID:200918", "title": "Cyclic AMP, the microtubule-microfilament system, and cancer.", "content": "Additional evidence is presented for the previously proposed existence in normal fibroblasts of a cyclic AMP-dependent network of microtubules and microfilaments, which is connected with cell membrane elements on one end and with nuclear structures on the other and whose disorganization leads to malignant transformation. In the presence of cyclic AMP derivatives sufficient to promote integrity of this network, cell growth limitation in suspension, increased transport of alpha-[14C]aminobutyrate, and the relatively tranquilized membrane of the normal fibroblast are also achieved. A pattern of distribution of actin and tubulin has been demonstrated showing aggregated actin deposits which are presumably responsible for the oscillatory knob activity of cells with the transformed habitus. Specific orientations of microtubular and filamentous elements with respect to the nucleus can be demonstrated. The hypothesis that the microtubular-microfilamentous structure conveys growth-regulatory information from the cell membrane to the nucleus and that its disorganization can lead to malignancy has been extended to explain various cellular manifestations.", "contents": "Cyclic AMP, the microtubule-microfilament system, and cancer. Additional evidence is presented for the previously proposed existence in normal fibroblasts of a cyclic AMP-dependent network of microtubules and microfilaments, which is connected with cell membrane elements on one end and with nuclear structures on the other and whose disorganization leads to malignant transformation. In the presence of cyclic AMP derivatives sufficient to promote integrity of this network, cell growth limitation in suspension, increased transport of alpha-[14C]aminobutyrate, and the relatively tranquilized membrane of the normal fibroblast are also achieved. A pattern of distribution of actin and tubulin has been demonstrated showing aggregated actin deposits which are presumably responsible for the oscillatory knob activity of cells with the transformed habitus. Specific orientations of microtubular and filamentous elements with respect to the nucleus can be demonstrated. The hypothesis that the microtubular-microfilamentous structure conveys growth-regulatory information from the cell membrane to the nucleus and that its disorganization can lead to malignancy has been extended to explain various cellular manifestations."}
{"id": "PMID:200919", "title": "Norepinephrine induces glial-specific enzyme activity in cultured plasma glioma cells.", "content": "Addition of 1 micronM 1-norepinephrine to cultures of C6TK- rat glioma cells caused a 2-fold increase in specific activity of the glial-specific enzyme 2':3'-cyclic nucleotide 3'-phosphohydrolase (nucleoside-2':3'-cyclic-phosphate 3'-nucleotidohydrolase, EC 3.1.4.16). Specific activity could also be stimulated by analogues of 3':5'-cyclic AMP, and the effect of norepinephrine could be blocked by beta-adrenergic receptor antagonists but not by alpha-adrenergic antagonists. Norepinephrine or cyclic AMP analogues also increased the specific activity of this enzyme in other clones of glioma and Schwannoma cells and in glioma X neuroblastoma cell hybrids. These results show that the stimulatory effect of norepinephrine on cyclic AMP concentrations in glioma cells leads ultimately to a stimulation of glial-specific cell funtion.", "contents": "Norepinephrine induces glial-specific enzyme activity in cultured plasma glioma cells. Addition of 1 micronM 1-norepinephrine to cultures of C6TK- rat glioma cells caused a 2-fold increase in specific activity of the glial-specific enzyme 2':3'-cyclic nucleotide 3'-phosphohydrolase (nucleoside-2':3'-cyclic-phosphate 3'-nucleotidohydrolase, EC 3.1.4.16). Specific activity could also be stimulated by analogues of 3':5'-cyclic AMP, and the effect of norepinephrine could be blocked by beta-adrenergic receptor antagonists but not by alpha-adrenergic antagonists. Norepinephrine or cyclic AMP analogues also increased the specific activity of this enzyme in other clones of glioma and Schwannoma cells and in glioma X neuroblastoma cell hybrids. These results show that the stimulatory effect of norepinephrine on cyclic AMP concentrations in glioma cells leads ultimately to a stimulation of glial-specific cell funtion."}
{"id": "PMID:200920", "title": "Tritium suicide selection of mammalian cell mutants defective in the transport of neutral amino acids.", "content": "Mouse lymphocytic cells of the established line GF-14 were allowed to accumulate intracellular 3H-labeled aminoisobutyric acid (AIB), frozen, and stored over liquid N2. After internal radiation had reduced survival to 1 in 10(4), survivors were plated and tested for their ability to transport AIB. Out of 200 clones tested, two (designated GF-17 and GF-18) were found to have reductions to 13-35% of the parent in the rate of transport of AIB, L-alanine, L-proline, and L-serine; GF-18 also showed significant reductions in the rate of transport of L-glutamate and DL-cysteine. Little or no change was observed for 10 other amino acids or for thymidine. Kinetic analyses revealed that the mutants were not altered in Km for AIB uptake, but had Vmax values approximately 20% the value of the parent strain, GF-14, suggesting that either the number of AIB transport sites or the turnover rate of the sites has been reduced in the two mutants.", "contents": "Tritium suicide selection of mammalian cell mutants defective in the transport of neutral amino acids. Mouse lymphocytic cells of the established line GF-14 were allowed to accumulate intracellular 3H-labeled aminoisobutyric acid (AIB), frozen, and stored over liquid N2. After internal radiation had reduced survival to 1 in 10(4), survivors were plated and tested for their ability to transport AIB. Out of 200 clones tested, two (designated GF-17 and GF-18) were found to have reductions to 13-35% of the parent in the rate of transport of AIB, L-alanine, L-proline, and L-serine; GF-18 also showed significant reductions in the rate of transport of L-glutamate and DL-cysteine. Little or no change was observed for 10 other amino acids or for thymidine. Kinetic analyses revealed that the mutants were not altered in Km for AIB uptake, but had Vmax values approximately 20% the value of the parent strain, GF-14, suggesting that either the number of AIB transport sites or the turnover rate of the sites has been reduced in the two mutants."}
{"id": "PMID:200921", "title": "Identification of amber and ochre mutants of the human virus Ad2+ND1.", "content": "Although human adenoviruses grow poorly in monkey cells, this defect can be overcome either by coinfection of cells with simian virus 40 (SV40) or by insertion of the relevant portion of the SV40 genome into the adenovirus genome to form an adenovirus-SV40 hybrid virus. The nondefective adenovirus-2-SV40 hybrid virus, Ad2+ND1, contains an insertion of 17% of the SV40 genome, which codes for at least part of a 30,000 dalton protein. A set of Ad2+ND1 host-range mutants that have lost the ability to grow in monkey cells and behave as point mutants fail to synthesize the 30,000 dalton ND1 protein. Translation in vitro of SV40-specific mRNA from mutant-infected cells produces unique short polypeptides instead of the 30,000 dalton protein. Here we show that this set of host-range mutants includes both ochre and amber nonsense mutations. When the SV40-specific mRNA from the host-range mutants is translated in vitro to produce the polypeptide fragments, yeast suppressor tRNA can partially restore synthesis of wild-type-size 30,000 dalton protein. By this assay, one mutant is ochre and two are amber.", "contents": "Identification of amber and ochre mutants of the human virus Ad2+ND1. Although human adenoviruses grow poorly in monkey cells, this defect can be overcome either by coinfection of cells with simian virus 40 (SV40) or by insertion of the relevant portion of the SV40 genome into the adenovirus genome to form an adenovirus-SV40 hybrid virus. The nondefective adenovirus-2-SV40 hybrid virus, Ad2+ND1, contains an insertion of 17% of the SV40 genome, which codes for at least part of a 30,000 dalton protein. A set of Ad2+ND1 host-range mutants that have lost the ability to grow in monkey cells and behave as point mutants fail to synthesize the 30,000 dalton ND1 protein. Translation in vitro of SV40-specific mRNA from mutant-infected cells produces unique short polypeptides instead of the 30,000 dalton protein. Here we show that this set of host-range mutants includes both ochre and amber nonsense mutations. When the SV40-specific mRNA from the host-range mutants is translated in vitro to produce the polypeptide fragments, yeast suppressor tRNA can partially restore synthesis of wild-type-size 30,000 dalton protein. By this assay, one mutant is ochre and two are amber."}
{"id": "PMID:200922", "title": "In vivo and in vitro phosphorylation of rat liver fructose-1,6-bisphosphatase.", "content": "Incorporation of 32P from [gamma-32P]ATP into a homogenous preparation of rat hepatic fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphatase 1-phosphohydrolase, EC 3.1.3.11) was catalyzed by a homogeneous preparation of the catalytic subunit of cyclic AMP-dependent protein kinase from bovine liver. Approximately 4 mol of phosphate were incorporated per mol of the tetrameric enzyme. This phosphorylation was associated with an increase in enzyme activity. In addition, in vivo phosphorylation of the enzyme was observed after injection of radioactive inorganic phosphate into rats and subsequent isolation of the enzyme by conventional purification methods and by immunoprecipitation. All of the labeled phosphate incorporation into the enzyme, both in vitro and in vivo, was precipitated by antibody specific for the enzyme. Furthermore, the 32Pi counts were coincident with the enzyme subunit band when the immunoprecipitates were examined by sodium dodecyl sulfate/disc gel electrophoresis. Acid hydrolysis of the immunoprecipitated enzyme that was phosphorylated in vitro revealed that only seryl residues were labeled. On the basis of the concentration of protein kinase (0.2-1.0 muM) necessary to phosphorylate physiological amounts of fructose-1,6-bisphosphatase (1.0-4.0 muM), it is suggested that cyclic AMP-dependent protein kinase may catalyze the phosphorylation of fructose-1,6-bisphosphatase in vivo.", "contents": "In vivo and in vitro phosphorylation of rat liver fructose-1,6-bisphosphatase. Incorporation of 32P from [gamma-32P]ATP into a homogenous preparation of rat hepatic fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphatase 1-phosphohydrolase, EC 3.1.3.11) was catalyzed by a homogeneous preparation of the catalytic subunit of cyclic AMP-dependent protein kinase from bovine liver. Approximately 4 mol of phosphate were incorporated per mol of the tetrameric enzyme. This phosphorylation was associated with an increase in enzyme activity. In addition, in vivo phosphorylation of the enzyme was observed after injection of radioactive inorganic phosphate into rats and subsequent isolation of the enzyme by conventional purification methods and by immunoprecipitation. All of the labeled phosphate incorporation into the enzyme, both in vitro and in vivo, was precipitated by antibody specific for the enzyme. Furthermore, the 32Pi counts were coincident with the enzyme subunit band when the immunoprecipitates were examined by sodium dodecyl sulfate/disc gel electrophoresis. Acid hydrolysis of the immunoprecipitated enzyme that was phosphorylated in vitro revealed that only seryl residues were labeled. On the basis of the concentration of protein kinase (0.2-1.0 muM) necessary to phosphorylate physiological amounts of fructose-1,6-bisphosphatase (1.0-4.0 muM), it is suggested that cyclic AMP-dependent protein kinase may catalyze the phosphorylation of fructose-1,6-bisphosphatase in vivo."}
{"id": "PMID:200923", "title": "Enzyme replacement therapy in Gaucher's disease: preliminary clinical trial of a new enzyme preparation.", "content": "A patient with far-advanced adult type Gaucher's disease was treated with solubilized, highly purified placental glucocerebrosidase administered after entrapment in human erythrocytes or by direct intravenous injection. In some instances the enzyme-containing erythrocytes were coated with gamma globulin. No toxic side effects were observed after enzyme infusion. There were suggestive, but not conclusive, findings that enzyme infusion may have been beneficial. After therapy, there was a decrease in transfusion requirement, some improvement of liver function, possible decrease in liver size, and relief of subjective symptoms. Erythrocyte and plasma glucocerebroside levels were unchanged during therapy, but there was a possibly significant decrease in leukocyte and platelet levels of the glycolipid. No changes occurred in serum acid phosphatase or angiotensin-converting enzyme activity.", "contents": "Enzyme replacement therapy in Gaucher's disease: preliminary clinical trial of a new enzyme preparation. A patient with far-advanced adult type Gaucher's disease was treated with solubilized, highly purified placental glucocerebrosidase administered after entrapment in human erythrocytes or by direct intravenous injection. In some instances the enzyme-containing erythrocytes were coated with gamma globulin. No toxic side effects were observed after enzyme infusion. There were suggestive, but not conclusive, findings that enzyme infusion may have been beneficial. After therapy, there was a decrease in transfusion requirement, some improvement of liver function, possible decrease in liver size, and relief of subjective symptoms. Erythrocyte and plasma glucocerebroside levels were unchanged during therapy, but there was a possibly significant decrease in leukocyte and platelet levels of the glycolipid. No changes occurred in serum acid phosphatase or angiotensin-converting enzyme activity."}
{"id": "PMID:200924", "title": "Recessive dystrophic epidermolysis bullosa: evidence for an altered collagenase in fibroblast cultures.", "content": "Collagenase has been implicated in the pathogenesis of blister formation in recessive dystrophic epidermolysis bullosa. In order to examine whether aberrations in this enzyme are important in the disease, fibroblast cultures from two patients were used to compare the properties of the collagenases from the mutant cells with those from control fibroblast lines. Purified procollagenase preparations from the mutant fibroblasts were significantly more thermolabile at low Ca2+ concentration than control enzymes. They also showed a decrease in affinity for Ca2+, a cofactor required both for enzyme activity and thermal stability. In addition, the collagenase from each mutant line displayed diminished specific activity, expressed as activity per unit of immunoreactive protein, with a mean value of 39% of control for one patient's enzyme and 16% for the other. The data support the postulate that, in these two patients, the altered collagenase is the result of a structural gene mutation, a defect in the post-translational modification of the enzyme, or a mutation in a gene regulating the normal degradation of collagenase.", "contents": "Recessive dystrophic epidermolysis bullosa: evidence for an altered collagenase in fibroblast cultures. Collagenase has been implicated in the pathogenesis of blister formation in recessive dystrophic epidermolysis bullosa. In order to examine whether aberrations in this enzyme are important in the disease, fibroblast cultures from two patients were used to compare the properties of the collagenases from the mutant cells with those from control fibroblast lines. Purified procollagenase preparations from the mutant fibroblasts were significantly more thermolabile at low Ca2+ concentration than control enzymes. They also showed a decrease in affinity for Ca2+, a cofactor required both for enzyme activity and thermal stability. In addition, the collagenase from each mutant line displayed diminished specific activity, expressed as activity per unit of immunoreactive protein, with a mean value of 39% of control for one patient's enzyme and 16% for the other. The data support the postulate that, in these two patients, the altered collagenase is the result of a structural gene mutation, a defect in the post-translational modification of the enzyme, or a mutation in a gene regulating the normal degradation of collagenase."}
{"id": "PMID:200925", "title": "Comparison of Epstein-Barr viral DNAs in Burkitt lymphoma biopsy cells and in cells clonally transformed in vitro.", "content": "The nucleotide sequences of intracellular Epstein-Barr viral DNAs in tumor biopsy cells of clones independently transformed in vitro were generally compared by determing the electrophoretic mobilities of restriction endonuclease cleavage fragments of the viral DNA. To carry out this comparison, cleaved cell DNAs were electrophoresed in agarose gels and transferred to nitrocellulose paper, and the immobilized viral species were identified by hybridization with purified, viral DNA labeled in vitro. These studies lead to three findings: (i) The complexities of all of the intracellular viral DNAs are similar to one another and to that of purified virion DNA. (II) There are small differences in the cleavage patterns of some viral DNAs, but the differences of the cleavage patterns of the viral DNA resident in the tumor cells and in the cells transformed in vitro are not more pronounced than those found between the different clones of the cells transformed in vitro. (iii) All of the viral DNA species contain a repeated sequence. The first two conclusions indicate that the Epstein-Barr virus strain studied in the laboratory appears indistinguishable from that associated with Burkitt lymphoma.", "contents": "Comparison of Epstein-Barr viral DNAs in Burkitt lymphoma biopsy cells and in cells clonally transformed in vitro. The nucleotide sequences of intracellular Epstein-Barr viral DNAs in tumor biopsy cells of clones independently transformed in vitro were generally compared by determing the electrophoretic mobilities of restriction endonuclease cleavage fragments of the viral DNA. To carry out this comparison, cleaved cell DNAs were electrophoresed in agarose gels and transferred to nitrocellulose paper, and the immobilized viral species were identified by hybridization with purified, viral DNA labeled in vitro. These studies lead to three findings: (i) The complexities of all of the intracellular viral DNAs are similar to one another and to that of purified virion DNA. (II) There are small differences in the cleavage patterns of some viral DNAs, but the differences of the cleavage patterns of the viral DNA resident in the tumor cells and in the cells transformed in vitro are not more pronounced than those found between the different clones of the cells transformed in vitro. (iii) All of the viral DNA species contain a repeated sequence. The first two conclusions indicate that the Epstein-Barr virus strain studied in the laboratory appears indistinguishable from that associated with Burkitt lymphoma."}
{"id": "PMID:200926", "title": "Translation of 35S and of subgenomic regions of avian sarcoma virus RNA.", "content": "Rabbit antiserum monospecific for an internal structural protein, p27, of avian sarcoma viruses (ASV) was found to immunoprecipitate polypeptides with molecular weights (Mr) of 180,000 and 76,000 from cell-free reticulocyte lysates programmed by ASV 35S RNA and also from lysates of ASV-infected cells. In addition, the Mr 180,000 protein was also precipitated by antiserum raised against virion DNA polymerase, suggesting that is a product of the two genes nearest the 5' end of virion 35S RNA. We have also investigated the ability of subgenomic portions of virion RNA to program cell-free protein synthesis. A 10-12S poly(A)-containing fragment of RNA from both nondefective and transformation-defective ASV directed the synthesis of a polypeptide of Mr 29,000 immunologically unrelated to the gs antigens; 20-24S poly(A)-containing RNA from nondefective ASV directed the synthesis of a polypeptide of Mr 60,000 not found when a similar RNA preparation from transformation-defective ASV was translated, suggesting that it is the product of the ASV src gene. These results indicate that internal initiation sites for protein synthesis exist on the 35S RNA genome.", "contents": "Translation of 35S and of subgenomic regions of avian sarcoma virus RNA. Rabbit antiserum monospecific for an internal structural protein, p27, of avian sarcoma viruses (ASV) was found to immunoprecipitate polypeptides with molecular weights (Mr) of 180,000 and 76,000 from cell-free reticulocyte lysates programmed by ASV 35S RNA and also from lysates of ASV-infected cells. In addition, the Mr 180,000 protein was also precipitated by antiserum raised against virion DNA polymerase, suggesting that is a product of the two genes nearest the 5' end of virion 35S RNA. We have also investigated the ability of subgenomic portions of virion RNA to program cell-free protein synthesis. A 10-12S poly(A)-containing fragment of RNA from both nondefective and transformation-defective ASV directed the synthesis of a polypeptide of Mr 29,000 immunologically unrelated to the gs antigens; 20-24S poly(A)-containing RNA from nondefective ASV directed the synthesis of a polypeptide of Mr 60,000 not found when a similar RNA preparation from transformation-defective ASV was translated, suggesting that it is the product of the ASV src gene. These results indicate that internal initiation sites for protein synthesis exist on the 35S RNA genome."}
{"id": "PMID:200927", "title": "Friend strain of spleen focus-forming virus is a recombinant between ecotropic murine type C virus and the env gene region of xenotropic type C virus.", "content": "The spleen focus-forming virus (SFFV), a replication-defective murine leukemia virus that causes the rapid transformation of certain hematopoietic target cells, has acquired specific xenotropic viral genetic information not contained in Friend helper virus. In the current studies, it is shown that a cDNA that represents a xenotropic virus portion of SFFV detects genetic sequences derived from the env gene region of murine xenotropic virus. The significance of the acquisition of these xenotropic viral sequences by SFFV is discussed with regard to their possible role in the rapid leukemogenicity of SFFV, and an analogy is drawn between the formation of SFFV and the formation of the Kirsten and Harvey sarcoma viruses.", "contents": "Friend strain of spleen focus-forming virus is a recombinant between ecotropic murine type C virus and the env gene region of xenotropic type C virus. The spleen focus-forming virus (SFFV), a replication-defective murine leukemia virus that causes the rapid transformation of certain hematopoietic target cells, has acquired specific xenotropic viral genetic information not contained in Friend helper virus. In the current studies, it is shown that a cDNA that represents a xenotropic virus portion of SFFV detects genetic sequences derived from the env gene region of murine xenotropic virus. The significance of the acquisition of these xenotropic viral sequences by SFFV is discussed with regard to their possible role in the rapid leukemogenicity of SFFV, and an analogy is drawn between the formation of SFFV and the formation of the Kirsten and Harvey sarcoma viruses."}
{"id": "PMID:200928", "title": "Biochemical evidence that MCF murine leukemia viruses are envelope (env) gene recombinants.", "content": "Recently, a novel class of murine type C virus (MCF), some strains of which are highly oncogenic in the AKR acceleration test, has been isolated from premalignant and malignant thymuses of AKR mice. The biology of these viruses suggested that MCFs are the product of recombination between endogenous ecotropic and xenotropic viruses and, further, that the recombination has taken place within the envelope (env) gene which encodes the surface glycoprotein (gp70) of the virion. We have compared by tryptic peptide analysis, the gp70s of four MCF isolates with the gp70s of various possible parental viruses. In addition, we have compared the tryptic peptides of the gag gene products p30 and p15 from several of these viruses. The results allow the following conclusions: (i) the gp70s of the MCF viruses are not identical to one another and are different from the gp70s of the possible parental viruses tested; (ii) the MCF virus gp70s have tryptic peptides in common with xenotropic virus gp70s as well as with ecotropic virus gp70s; and (iii) the gap region protein, p30, of the MCFs tested is identical to p30 of AKR ecotropic virus (Akv-1 or Akv-2) and distinct from p30 of xenotropic viruses, suggesting that the 5' end of the recombinant viruses is of Akv origin. The findings are discussed with respect to the possible role a recombinant virus might play in leukemogenesis in AKR mice.", "contents": "Biochemical evidence that MCF murine leukemia viruses are envelope (env) gene recombinants. Recently, a novel class of murine type C virus (MCF), some strains of which are highly oncogenic in the AKR acceleration test, has been isolated from premalignant and malignant thymuses of AKR mice. The biology of these viruses suggested that MCFs are the product of recombination between endogenous ecotropic and xenotropic viruses and, further, that the recombination has taken place within the envelope (env) gene which encodes the surface glycoprotein (gp70) of the virion. We have compared by tryptic peptide analysis, the gp70s of four MCF isolates with the gp70s of various possible parental viruses. In addition, we have compared the tryptic peptides of the gag gene products p30 and p15 from several of these viruses. The results allow the following conclusions: (i) the gp70s of the MCF viruses are not identical to one another and are different from the gp70s of the possible parental viruses tested; (ii) the MCF virus gp70s have tryptic peptides in common with xenotropic virus gp70s as well as with ecotropic virus gp70s; and (iii) the gap region protein, p30, of the MCFs tested is identical to p30 of AKR ecotropic virus (Akv-1 or Akv-2) and distinct from p30 of xenotropic viruses, suggesting that the 5' end of the recombinant viruses is of Akv origin. The findings are discussed with respect to the possible role a recombinant virus might play in leukemogenesis in AKR mice."}
{"id": "PMID:200929", "title": "Nerve growth factor increases activity of ornithine decarboxylase in superior cervical ganglia of young rats.", "content": "Nerve growth factor produces a rapid increase in the activity of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) in superior cervical ganglia of young rats in vivo and in vitro. Maximum activity occurs 6-7 hr after the addition of nerve growth factor. The nerve growth factor-mediated increase in ornithine decarboxylase activity in vitro can be prevented by the addition of cycloheximide, actinomycin D, or antibody to nerve growth factor. A number of other agents were tested for their ability to increase ornithine decarboxylase were tested for their ability to increase ornithine decarboxylase activity in the ganglia; only nerve growth factor, and, to a slight extent, insulin were able to raise the activity of the enzyme. High concentrations of dibutyryl cyclic AMP (10 mM) were able to mimic the effect of nerve growth factor.", "contents": "Nerve growth factor increases activity of ornithine decarboxylase in superior cervical ganglia of young rats. Nerve growth factor produces a rapid increase in the activity of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) in superior cervical ganglia of young rats in vivo and in vitro. Maximum activity occurs 6-7 hr after the addition of nerve growth factor. The nerve growth factor-mediated increase in ornithine decarboxylase activity in vitro can be prevented by the addition of cycloheximide, actinomycin D, or antibody to nerve growth factor. A number of other agents were tested for their ability to increase ornithine decarboxylase were tested for their ability to increase ornithine decarboxylase activity in the ganglia; only nerve growth factor, and, to a slight extent, insulin were able to raise the activity of the enzyme. High concentrations of dibutyryl cyclic AMP (10 mM) were able to mimic the effect of nerve growth factor."}
{"id": "PMID:200930", "title": "Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme.", "content": "A target protein for nalidixic and oxolinic acids in Escherichia coli, the nalA gene product (Pnal), was purified to homogeneity as judged by gel electrophoresis, using an in vitro complementation assay. It is a dimer of identical 110,000-dalton subunits. A polypeptide of this molecular weight is uniquely induced by a lambda nalA transducing phage, thereby showing that the purified Pnal is a product of the nalA gene. Nalidixic and oxolinic acids inhibit DNA gyrase activity and induce formation of a relaxation complex analogue. Treatment of the complex with sodium dodecyl sulfate causes a doublestrand break in the DNA substrate and the resulting linear molecule seems covalently bound to protein. Complex formation, unlike the introduction of supertwists, does not require ATP or relaxed circular DNA and is insensitive to novobiocin. DNA gyrase from a strain with a nalA mutation conferring drug resistance (nalA(r)) is 1/100 as sensitive to oxolinic and nalidixic acids with respect to inhibition of supertwisting and induction of the pre-linearization complex. Addition of Pnal restores drug sensitivity and stimulates DNA gyrase activity. DNA gyrase preparations and Pnal catalyze a third reaction sensitive to nalidixic and oxolinic acids, the ATP-independent relaxation of supertwister DNA. Relaxation by gyrase from nalA(r) cells is drug resistant. The nicking-closing activity is distinct from E. coli omega protein in several properties, including the ability to relax positively supertwisted DNA. We postulate that the nalA gene product occurs in two molecular forms, as Pnal and as a gyrase component. Both forms catalyze nicking-closing, and inhibition of this activity by nalidixic and oxolinic acids may account for the inhibition of DNA synthesis by these drugs.", "contents": "Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. A target protein for nalidixic and oxolinic acids in Escherichia coli, the nalA gene product (Pnal), was purified to homogeneity as judged by gel electrophoresis, using an in vitro complementation assay. It is a dimer of identical 110,000-dalton subunits. A polypeptide of this molecular weight is uniquely induced by a lambda nalA transducing phage, thereby showing that the purified Pnal is a product of the nalA gene. Nalidixic and oxolinic acids inhibit DNA gyrase activity and induce formation of a relaxation complex analogue. Treatment of the complex with sodium dodecyl sulfate causes a doublestrand break in the DNA substrate and the resulting linear molecule seems covalently bound to protein. Complex formation, unlike the introduction of supertwists, does not require ATP or relaxed circular DNA and is insensitive to novobiocin. DNA gyrase from a strain with a nalA mutation conferring drug resistance (nalA(r)) is 1/100 as sensitive to oxolinic and nalidixic acids with respect to inhibition of supertwisting and induction of the pre-linearization complex. Addition of Pnal restores drug sensitivity and stimulates DNA gyrase activity. DNA gyrase preparations and Pnal catalyze a third reaction sensitive to nalidixic and oxolinic acids, the ATP-independent relaxation of supertwister DNA. Relaxation by gyrase from nalA(r) cells is drug resistant. The nicking-closing activity is distinct from E. coli omega protein in several properties, including the ability to relax positively supertwisted DNA. We postulate that the nalA gene product occurs in two molecular forms, as Pnal and as a gyrase component. Both forms catalyze nicking-closing, and inhibition of this activity by nalidixic and oxolinic acids may account for the inhibition of DNA synthesis by these drugs."}
{"id": "PMID:200931", "title": "Occurrence of partial deletion and substitution of the src gene in the RNA genome of avian sarcoma virus.", "content": "The genome size of 20 transformation-defective (td) viruses derived from different strains of Rous sarcoma viruses [Prague (subgroups A and C), Schmidt-Ruppin (subgroups A and D) (SR-D), Bratislava 77, and Carr-Zilber subgroup D)] was examined by polyacrylamide gel electrophoresis. All of the td viruses except td SR-D have 35S RNA of the same size-i.e., class b RNA. Two of five td SR-D viruses examined have a slightly larger RNA, corresponding to a td deletion that is about 25% smaller than that of class b RNA. However, the RNase T(1)-oligonucleotide fingerprints of all the td SR-D viruses are identical, lacking two sarcoma-specific oligonucleotides. The fingerprints of these viruses also showed a minor oligonucleotide present at very low concentration. A study of heteroduplex molecules formed between genome-length cDNA made from wild-type SR-D and 35S RNA of td SR-D showed a deletion loop of 2.0 and 1.5 kilobases, respectively, at the map position of the src gene for these two classes of td SR-D viruses, confirming the results of polyacrylamide gel electrophoresis. In addition, some heteroduplex molecules with a substitution loop of 0.6-0.7 kilobase at the same site as the deletion loop were observed in all five of the td SR-D viruses. We conclude that some of the td SR-D viruses have a partially deleted src gene and that all of the td SR-D viruses have incorporated heterologous sequences of distinct length in some RNA molecules at the position of the src gene. The nature and origin of these heterologous sequences are discussed.", "contents": "Occurrence of partial deletion and substitution of the src gene in the RNA genome of avian sarcoma virus. The genome size of 20 transformation-defective (td) viruses derived from different strains of Rous sarcoma viruses [Prague (subgroups A and C), Schmidt-Ruppin (subgroups A and D) (SR-D), Bratislava 77, and Carr-Zilber subgroup D)] was examined by polyacrylamide gel electrophoresis. All of the td viruses except td SR-D have 35S RNA of the same size-i.e., class b RNA. Two of five td SR-D viruses examined have a slightly larger RNA, corresponding to a td deletion that is about 25% smaller than that of class b RNA. However, the RNase T(1)-oligonucleotide fingerprints of all the td SR-D viruses are identical, lacking two sarcoma-specific oligonucleotides. The fingerprints of these viruses also showed a minor oligonucleotide present at very low concentration. A study of heteroduplex molecules formed between genome-length cDNA made from wild-type SR-D and 35S RNA of td SR-D showed a deletion loop of 2.0 and 1.5 kilobases, respectively, at the map position of the src gene for these two classes of td SR-D viruses, confirming the results of polyacrylamide gel electrophoresis. In addition, some heteroduplex molecules with a substitution loop of 0.6-0.7 kilobase at the same site as the deletion loop were observed in all five of the td SR-D viruses. We conclude that some of the td SR-D viruses have a partially deleted src gene and that all of the td SR-D viruses have incorporated heterologous sequences of distinct length in some RNA molecules at the position of the src gene. The nature and origin of these heterologous sequences are discussed."}
{"id": "PMID:200932", "title": "Immunologic selection against simian virus-40 transformed cells: concomitnat loss of viral antigens and early viral gene sequences.", "content": "A clonal line of highly oncogenic \"spontaneously transformed\" mouse cells (T AL/N clone 3) was transformed in tissue culture by simian virus 40 (SV40) and subsequently recloned. The clone of SV40-transformed cells (subclone 1) expressed SV40-specific T (nuclear) and transplantation antigens but was 100 times less tumorigenic than the parent T AL/N clone 3 cells. When large numbers of subclone 1 cells (10(4)-10(5)) were injected into syngeneic AL/N mice, tumors were produced. From the tumors, cell lines were established in culture, all of which were consistently negative for T antigen. Tumor lines tested were found not to contain SV40-specific transplantation antigen and had again become highly tumorigenic. The original subclone 1 cells contained about one copy of SV40 DNA per diploid amount of cell DNA, as well as RNA complementary to the early region of the SV40 genome. The T antigen-negative cells from tumor line 124 contained approximately 0.5 copy of SV40 DNA per diploid equivalent and did not synthesize any detectable virus-specific RNA. Reassociation kinetic analysis with restriction enzyme fragments of viral DNA demonstrated that the cells from tumor line 124 (and also the clones of this line) had lost DNA sequences predominantly from the early region of the SV40 genome. The results indicate that a set of stably integrated SV40 DNA sequences can be present in a cell without the expression of viral antigens.", "contents": "Immunologic selection against simian virus-40 transformed cells: concomitnat loss of viral antigens and early viral gene sequences. A clonal line of highly oncogenic \"spontaneously transformed\" mouse cells (T AL/N clone 3) was transformed in tissue culture by simian virus 40 (SV40) and subsequently recloned. The clone of SV40-transformed cells (subclone 1) expressed SV40-specific T (nuclear) and transplantation antigens but was 100 times less tumorigenic than the parent T AL/N clone 3 cells. When large numbers of subclone 1 cells (10(4)-10(5)) were injected into syngeneic AL/N mice, tumors were produced. From the tumors, cell lines were established in culture, all of which were consistently negative for T antigen. Tumor lines tested were found not to contain SV40-specific transplantation antigen and had again become highly tumorigenic. The original subclone 1 cells contained about one copy of SV40 DNA per diploid amount of cell DNA, as well as RNA complementary to the early region of the SV40 genome. The T antigen-negative cells from tumor line 124 contained approximately 0.5 copy of SV40 DNA per diploid equivalent and did not synthesize any detectable virus-specific RNA. Reassociation kinetic analysis with restriction enzyme fragments of viral DNA demonstrated that the cells from tumor line 124 (and also the clones of this line) had lost DNA sequences predominantly from the early region of the SV40 genome. The results indicate that a set of stably integrated SV40 DNA sequences can be present in a cell without the expression of viral antigens."}
{"id": "PMID:200933", "title": "Glucocorticoids increase the responsiveness of cells in culture to prostaglandin E1.", "content": "The influence of steroid hormones on the response of human astrocytoma cells (1321N1) to prostaglandin E(1) (PGE(1)) has been investigated. Responsiveness to PGE(1) was determined by measuring the conversion of [(3)H]ATP to cyclic [(3)H]AMP in cells prelabeled with [(3)H]adenine. After incubation of the cells with dexamethasone, a marked increase in both the maximal effect (2- to 3-fold) and the potency (5-fold) of PGE(1) was observed. The effect was specific for the action of PGE(1) in that no change in the response of the cells to isoproterenol was observed. The EC(50) for dexamethasone was 0.001 muM and the effect was dependent on the presence of serum. The effect of dexamethasone was first observed after a 30- to 60-min lag and was maximal by 6-8 hr. Preconfluent cultures (3 days after seeding) exhibited optimal responsiveness to glucocorticoids. Both hydrocortisone and corticosterone mimicked the effect of dexamethasone but both were less potent. The action of dexamethasone was blocked by progesterone, testosterone, and 17alpha-methyltestosterone. Cycloheximide, at a concentration (1.0 mug/ml) that blocked protein synthesis (>90%) in 1321N1 cells, totally prevented the effect of dexamethasone on the response of the cells to PGE(1). Upon removal of dexamethasone from cells treated for 16 hr, responsiveness to PGE(1) returned to control levels with a half-time of 4 hr. Dexamethasone also was found to increase the response to PGE(1) of a Rous sarcoma virus-transformed human astrocytoma cell line and the WI-38 human fibroblast line. The most obvious interpretation of our findings is that glucocorticoids induce the synthesis of a protein that selectively modifies the sensitivity of adenylate cyclase to PGE(1).", "contents": "Glucocorticoids increase the responsiveness of cells in culture to prostaglandin E1. The influence of steroid hormones on the response of human astrocytoma cells (1321N1) to prostaglandin E(1) (PGE(1)) has been investigated. Responsiveness to PGE(1) was determined by measuring the conversion of [(3)H]ATP to cyclic [(3)H]AMP in cells prelabeled with [(3)H]adenine. After incubation of the cells with dexamethasone, a marked increase in both the maximal effect (2- to 3-fold) and the potency (5-fold) of PGE(1) was observed. The effect was specific for the action of PGE(1) in that no change in the response of the cells to isoproterenol was observed. The EC(50) for dexamethasone was 0.001 muM and the effect was dependent on the presence of serum. The effect of dexamethasone was first observed after a 30- to 60-min lag and was maximal by 6-8 hr. Preconfluent cultures (3 days after seeding) exhibited optimal responsiveness to glucocorticoids. Both hydrocortisone and corticosterone mimicked the effect of dexamethasone but both were less potent. The action of dexamethasone was blocked by progesterone, testosterone, and 17alpha-methyltestosterone. Cycloheximide, at a concentration (1.0 mug/ml) that blocked protein synthesis (>90%) in 1321N1 cells, totally prevented the effect of dexamethasone on the response of the cells to PGE(1). Upon removal of dexamethasone from cells treated for 16 hr, responsiveness to PGE(1) returned to control levels with a half-time of 4 hr. Dexamethasone also was found to increase the response to PGE(1) of a Rous sarcoma virus-transformed human astrocytoma cell line and the WI-38 human fibroblast line. The most obvious interpretation of our findings is that glucocorticoids induce the synthesis of a protein that selectively modifies the sensitivity of adenylate cyclase to PGE(1)."}
{"id": "PMID:200934", "title": "Characterization of a common precursor to corticotropin and beta-lipotropin: cell-free synthesis of the precursor and identification of corticotropin peptides in the molecule.", "content": "mRNA was isolated from cultures of AtT-20/D-16v tumor cells and translated in a mRNA-dependent reticulocyte cell-free system. The corticotropin (ACTH) product was purified by a double-antibody immunoprecipitation procedure using antisera specific for the alpha(1-24) sequence of ACTH. The product is shown by sodium dodecyl sulfate/gel electrophoresis and gel filtration on guanidine-HCl columns to be homogeneous with an apparent molecular weight (Mr) of 28,500. A product with the same molecular weight is synthesized when membrane-bound polysomes from D-16v cells are allowed to complete their nascent chains in a reticulocyte cell-free system. Mr 31,000 ACTH isolated from tumor cells has been separated into three proteins of different apparent Mr:29,000, 32,000, and 34,000. The cell-free product contains the same lysine-, methionine-, and phenylalanine-labeled tryptic peptides as the Mr 29,000 ACTH synthesized in the tumor cells. Tryptic peptide analysis also reveals the presence of the alpha(1-39) sequence in the Mr 28,500 cell-free product and suggests that there is only one copy of this sequence in the Mr 28,500 molecule.", "contents": "Characterization of a common precursor to corticotropin and beta-lipotropin: cell-free synthesis of the precursor and identification of corticotropin peptides in the molecule. mRNA was isolated from cultures of AtT-20/D-16v tumor cells and translated in a mRNA-dependent reticulocyte cell-free system. The corticotropin (ACTH) product was purified by a double-antibody immunoprecipitation procedure using antisera specific for the alpha(1-24) sequence of ACTH. The product is shown by sodium dodecyl sulfate/gel electrophoresis and gel filtration on guanidine-HCl columns to be homogeneous with an apparent molecular weight (Mr) of 28,500. A product with the same molecular weight is synthesized when membrane-bound polysomes from D-16v cells are allowed to complete their nascent chains in a reticulocyte cell-free system. Mr 31,000 ACTH isolated from tumor cells has been separated into three proteins of different apparent Mr:29,000, 32,000, and 34,000. The cell-free product contains the same lysine-, methionine-, and phenylalanine-labeled tryptic peptides as the Mr 29,000 ACTH synthesized in the tumor cells. Tryptic peptide analysis also reveals the presence of the alpha(1-39) sequence in the Mr 28,500 cell-free product and suggests that there is only one copy of this sequence in the Mr 28,500 molecule."}
{"id": "PMID:200935", "title": "Regulatory function of simian virus 40 DNA replication for late viral gene expression.", "content": "Inhibition of simian virus 40 (SV40) DNA synthesis prevents late but not early viral gene expression in infected cells. To test whether the late SV40 template specificity is elicited by replicative intermediate DNA molecules (RI-DNA), we isolated subcellular fractions containing RI-DNA from SV-40-infected monkey cells and microinjected these preparations into various cell lines under conditions in which viral DNA synthesis was blocked. Late SV40 gene expression (V-antigen synthesis) was obtained by microinjection of wild-type RI-DNA or temperature-sensitive mutant A7 RI-DNA preparations at 37 degrees or 41.5 degrees, respectively, while SV40 native superhelical DNA (DNA I) at a 10-fold higher concentration failed to induce V-antigen synthesis under the restrictive conditions. V-antigen synthesis was also obtained by microinjection of partially denatured SV40 DNA or a high number of randomly nicked DNA molecules (DNA II) in the absence of DNA synthesis; both single-stranded regions and nicks are specific features of RI-DNA molecules.", "contents": "Regulatory function of simian virus 40 DNA replication for late viral gene expression. Inhibition of simian virus 40 (SV40) DNA synthesis prevents late but not early viral gene expression in infected cells. To test whether the late SV40 template specificity is elicited by replicative intermediate DNA molecules (RI-DNA), we isolated subcellular fractions containing RI-DNA from SV-40-infected monkey cells and microinjected these preparations into various cell lines under conditions in which viral DNA synthesis was blocked. Late SV40 gene expression (V-antigen synthesis) was obtained by microinjection of wild-type RI-DNA or temperature-sensitive mutant A7 RI-DNA preparations at 37 degrees or 41.5 degrees, respectively, while SV40 native superhelical DNA (DNA I) at a 10-fold higher concentration failed to induce V-antigen synthesis under the restrictive conditions. V-antigen synthesis was also obtained by microinjection of partially denatured SV40 DNA or a high number of randomly nicked DNA molecules (DNA II) in the absence of DNA synthesis; both single-stranded regions and nicks are specific features of RI-DNA molecules."}
{"id": "PMID:200936", "title": "Dinucleoside pyrophosphate are substrates for T4-induced RNA ligase.", "content": "RNA ligase isolated from bacteriophage T4-infected Escherichia coli will utilize a number of different compounds with the general structure Ado-5'PP-X as substrates in an ATP-independent reaction. The P-X portions of these molecules are transferred to the 3'-hydroxyl of an oligoribonucleotide to form a phosphodiester bond, and the Ado-5'P (AMP) portion is released. AMP, CMP, GMP, UMP, dTMP, NMN, alphaNMN, reduced NMN, FMN, Rib-5P, phosphopantetheine, and cyanoethylphosphate all have been added to [Cyd-3H](Ap)3C from their corresponding AMP adducts. Contrary to the relative lack of specificity of RNA ligase for the P-X -group added, the failure of NADP+, deamino-NAD+, epsilonNCD+, epsilon NAD and CoA to react indicates that the enzyme shows a high degree of selectivity for the AMP portion of the substrate. The diversity of chemical groups that can be efficiently added suggests that this reaction of RNA ligase will prove useful for the modification of the 3' ends of RNA molecules.", "contents": "Dinucleoside pyrophosphate are substrates for T4-induced RNA ligase. RNA ligase isolated from bacteriophage T4-infected Escherichia coli will utilize a number of different compounds with the general structure Ado-5'PP-X as substrates in an ATP-independent reaction. The P-X portions of these molecules are transferred to the 3'-hydroxyl of an oligoribonucleotide to form a phosphodiester bond, and the Ado-5'P (AMP) portion is released. AMP, CMP, GMP, UMP, dTMP, NMN, alphaNMN, reduced NMN, FMN, Rib-5P, phosphopantetheine, and cyanoethylphosphate all have been added to [Cyd-3H](Ap)3C from their corresponding AMP adducts. Contrary to the relative lack of specificity of RNA ligase for the P-X -group added, the failure of NADP+, deamino-NAD+, epsilonNCD+, epsilon NAD and CoA to react indicates that the enzyme shows a high degree of selectivity for the AMP portion of the substrate. The diversity of chemical groups that can be efficiently added suggests that this reaction of RNA ligase will prove useful for the modification of the 3' ends of RNA molecules."}
{"id": "PMID:200937", "title": "Activation of hormone-sensitive lipase and phosphorylase kinase by purified cyclic GMP-dependent protein kinase.", "content": "Cyclic GMP-dependent protein kinase, purified to homogeneity from bovine lung, was shown to activate hormone-sensitive lipase partially purified from chicken adipose tissue. The degree of activation was the same as that effected by cyclic AMP-dependent protein kinase although higher concentrations of the cyclic GMP-dependent enzyme were required (relative activities expressed in terms of histone H2b phosphorylation units). Activation by cyclic AMP-dependent protein kinase was completely blocked by the heat-stable protein kinase inhibitor protein from skeletal muscle but activation by the cyclic GMP enzyme was not inhibited. Lipase fully activated by cyclic AMP-dependent protein kinase showed no further change in activity when treated with cyclic GMP-dependent protein kinase. Lipase activated by cyclic GMP-dependent protein kinase was reversibly deactivated by purified phosphorylase phosphatase (from bovine heart); full activity was restored by reincubation with cyclic GMP and cyclic GMP-dependent protein kinase. Cholesterol esterase activity in the chicken adipose tissue fraction, previously shown to be activated along with the triglyceride lipase by cyclic AMP-dependent protein kinase, was also activated by cyclic GMP-dependent protein kinase. Crude preparations of hormone-sensitive triglyceride lipase from human or rat adipose tissue and cholesterol esterase from rat adrenal were also activated by cyclic GMP-dependent protein kinase. Purified phosphorylase kinase (rabbit skeletal muscle) was also shown to be activated by cyclic GMP-dependent protein kinase. The present results, together with those of other workers on histone phosphorylation, suggest that the substrate specificities of cyclic GMP-dependent and cyclic AMP-dependent protein kinase may be similar. This is discussed in the light of a model recently proposed with regard to the relationship between the subunit structures of the two kinases. The physiologic significance of the findings remains to be established.", "contents": "Activation of hormone-sensitive lipase and phosphorylase kinase by purified cyclic GMP-dependent protein kinase. Cyclic GMP-dependent protein kinase, purified to homogeneity from bovine lung, was shown to activate hormone-sensitive lipase partially purified from chicken adipose tissue. The degree of activation was the same as that effected by cyclic AMP-dependent protein kinase although higher concentrations of the cyclic GMP-dependent enzyme were required (relative activities expressed in terms of histone H2b phosphorylation units). Activation by cyclic AMP-dependent protein kinase was completely blocked by the heat-stable protein kinase inhibitor protein from skeletal muscle but activation by the cyclic GMP enzyme was not inhibited. Lipase fully activated by cyclic AMP-dependent protein kinase showed no further change in activity when treated with cyclic GMP-dependent protein kinase. Lipase activated by cyclic GMP-dependent protein kinase was reversibly deactivated by purified phosphorylase phosphatase (from bovine heart); full activity was restored by reincubation with cyclic GMP and cyclic GMP-dependent protein kinase. Cholesterol esterase activity in the chicken adipose tissue fraction, previously shown to be activated along with the triglyceride lipase by cyclic AMP-dependent protein kinase, was also activated by cyclic GMP-dependent protein kinase. Crude preparations of hormone-sensitive triglyceride lipase from human or rat adipose tissue and cholesterol esterase from rat adrenal were also activated by cyclic GMP-dependent protein kinase. Purified phosphorylase kinase (rabbit skeletal muscle) was also shown to be activated by cyclic GMP-dependent protein kinase. The present results, together with those of other workers on histone phosphorylation, suggest that the substrate specificities of cyclic GMP-dependent and cyclic AMP-dependent protein kinase may be similar. This is discussed in the light of a model recently proposed with regard to the relationship between the subunit structures of the two kinases. The physiologic significance of the findings remains to be established."}
{"id": "PMID:200938", "title": "Role of nucleotides in tubulin polymerization: effect of guanylyl 5'-methylenediphosphonate.", "content": "Incubation of 48,000 X g rat brain supernatants for 30 min at 37 degrees with 1-2 mM guanylyl 5'-methylenediphosphonate [Gmp(CH2)pp] results in polymerization of 95-98% of the tubulin present. This is considerably more than the 50% polymerization that can be achieved with the natural nucleotide, GTP, under optimal conditions. Gmp(CH2)pp is also much more effective than GTP in inducing polymerization of purified tubulin. Assembly of microtubules with Gmp(CH2)pp occurs at tubulin concentrations one-third of those possible with GTP. Furthermore, with Gmp(CH2)pp, microtubule assembly does not require the high molecular weight basic proteins needed with GTP. Polymerization of tubulin by Gmp(CH2)pp is neither prevented nor reversed by concentrations of calcium (2 mM) that can either prevent microtubule assembly or disrupt already formed microtubules if the nucleotide used is GTP or guanylyl imidodiphosphate. When Ca2+ is added before or after microtubule assembly, electron microscopy of the Gmp(CH2)pp preparations reveals normal microtubules turning into twisted ribbons. Low temperature (4 degrees) can both prevent and disrupt the tubulin assembled Gmp(CH2)pp although disruption proceeds much more slowly when GTP is used.", "contents": "Role of nucleotides in tubulin polymerization: effect of guanylyl 5'-methylenediphosphonate. Incubation of 48,000 X g rat brain supernatants for 30 min at 37 degrees with 1-2 mM guanylyl 5'-methylenediphosphonate [Gmp(CH2)pp] results in polymerization of 95-98% of the tubulin present. This is considerably more than the 50% polymerization that can be achieved with the natural nucleotide, GTP, under optimal conditions. Gmp(CH2)pp is also much more effective than GTP in inducing polymerization of purified tubulin. Assembly of microtubules with Gmp(CH2)pp occurs at tubulin concentrations one-third of those possible with GTP. Furthermore, with Gmp(CH2)pp, microtubule assembly does not require the high molecular weight basic proteins needed with GTP. Polymerization of tubulin by Gmp(CH2)pp is neither prevented nor reversed by concentrations of calcium (2 mM) that can either prevent microtubule assembly or disrupt already formed microtubules if the nucleotide used is GTP or guanylyl imidodiphosphate. When Ca2+ is added before or after microtubule assembly, electron microscopy of the Gmp(CH2)pp preparations reveals normal microtubules turning into twisted ribbons. Low temperature (4 degrees) can both prevent and disrupt the tubulin assembled Gmp(CH2)pp although disruption proceeds much more slowly when GTP is used."}
{"id": "PMID:200939", "title": "Binding of the endogenous nonpeptide morphine-like compound to opiate receptors.", "content": "The endogenous central nervous tissue substance called MLC (morphine-like compound) is shown to bind to the opiate receptors of the mouse neuroblastoma X glioma hybrid cell line NG108-15. The interaction of MLC with these opiate receptors is noncooperative, as is the interaction of morphine, naloxone, and Leu-enkephalin with these receptors. A specific antibody to morphine will bind MLC but will not bind beta-endorphin, Leu-enkephalin, or Met-enkephalin. It would appear, therefore, that MLC can be considered to be a different type of endogenous ligand for the opiate receptor.", "contents": "Binding of the endogenous nonpeptide morphine-like compound to opiate receptors. The endogenous central nervous tissue substance called MLC (morphine-like compound) is shown to bind to the opiate receptors of the mouse neuroblastoma X glioma hybrid cell line NG108-15. The interaction of MLC with these opiate receptors is noncooperative, as is the interaction of morphine, naloxone, and Leu-enkephalin with these receptors. A specific antibody to morphine will bind MLC but will not bind beta-endorphin, Leu-enkephalin, or Met-enkephalin. It would appear, therefore, that MLC can be considered to be a different type of endogenous ligand for the opiate receptor."}
{"id": "PMID:200940", "title": "Cell-free synthesis of the precursor polypeptide for avian myeloblastosis virus DNA polymerase.", "content": "High molecular weight RNA (35S) isolated from avian myeloblastosis virus directs the cell-free synthesis of two prominent polypeptides of 180,000 and 76,000 molecular weight. The latter polypeptide has previously been identified as the precursor to the group-specific antigens of the virus (\"gag\" proteins) [Vogt, V. M., Eisenman, R. & Diggelmann, H. (1975) J. Mol. Biol. 96, 471-493]. Two-dimensional tryptic peptide analyses of the [35S]methionine-labeled peptides demonstrate that the 180,000-dalton product is a polyprotein that can account for all the peptides of the avian myeloblastosis virus DNA polymerase (DNA nucleotidyltransferase, EC 2.7.7.7) and those of the gag viral proteins. This is direct confirmation of the genomic order of the viral structural genes, placing the polymerase gene adjacent to the 5'-proximal gag gene of the virus. Furthermore, our findings suggest that the primary polymerase gene product is the beta subunit of the enzyme. These results are discussed in relation to the proposed structural gene map for the avian retraviruses and suggest a model for the in vivo processing of the viral polymerase.", "contents": "Cell-free synthesis of the precursor polypeptide for avian myeloblastosis virus DNA polymerase. High molecular weight RNA (35S) isolated from avian myeloblastosis virus directs the cell-free synthesis of two prominent polypeptides of 180,000 and 76,000 molecular weight. The latter polypeptide has previously been identified as the precursor to the group-specific antigens of the virus (\"gag\" proteins) [Vogt, V. M., Eisenman, R. & Diggelmann, H. (1975) J. Mol. Biol. 96, 471-493]. Two-dimensional tryptic peptide analyses of the [35S]methionine-labeled peptides demonstrate that the 180,000-dalton product is a polyprotein that can account for all the peptides of the avian myeloblastosis virus DNA polymerase (DNA nucleotidyltransferase, EC 2.7.7.7) and those of the gag viral proteins. This is direct confirmation of the genomic order of the viral structural genes, placing the polymerase gene adjacent to the 5'-proximal gag gene of the virus. Furthermore, our findings suggest that the primary polymerase gene product is the beta subunit of the enzyme. These results are discussed in relation to the proposed structural gene map for the avian retraviruses and suggest a model for the in vivo processing of the viral polymerase."}
{"id": "PMID:200941", "title": "Prostaglandin regulation of macrophage collagenase production.", "content": "The production of collagenase (EC 3.4.24.3) by endotoxin-stimulated macrophages was significantly inhibited by indomethacin, indicating that prostaglandins (PGs) mediate this effect. Inhibitions of collagenase production by indomethacin was overcome by addition of exogenous PGE2 at 10 nM whereas the addition of 0.1 and 1.0 micrometer PGE2 increased the enzyme production to 3 times that achieved by endotoxin. Although the addition of prostaglandin alone to macrophage cultures did not stimulate collagenase production, the simultaneous addition of PGE1 or PGE2 and endotoxin enhanced collagenase activity 2- to 10-fold. This increase was detectable at PGE concentrations of 10 nM and was optimal at 0.1-1.0 micrometer. PGF2alpha had little effect on either the enhancement of collagenase production by endotoxin-stimulated macrophages or its restoration in cultures inhibited by indomethacin. Radioimmunoassay of prostaglandins in the culture media revealed that macrophages exposed to endotoxin secreted 40-fold more PGE2 than did unstimulated cells. The increase in PGE2 was detected 4 hr after exposure to endotoxin and was maximal at 14 hr. The peak PGE2 concentrations in the culture media were similar to those of exogenous PGE2 (about 10 nM) needed to restore collagenase production in indomethacin-treated cultures. These findings demonstrate the involvement of PGE in the endotoxin-activation of macrophages with resultant production of collagenase.", "contents": "Prostaglandin regulation of macrophage collagenase production. The production of collagenase (EC 3.4.24.3) by endotoxin-stimulated macrophages was significantly inhibited by indomethacin, indicating that prostaglandins (PGs) mediate this effect. Inhibitions of collagenase production by indomethacin was overcome by addition of exogenous PGE2 at 10 nM whereas the addition of 0.1 and 1.0 micrometer PGE2 increased the enzyme production to 3 times that achieved by endotoxin. Although the addition of prostaglandin alone to macrophage cultures did not stimulate collagenase production, the simultaneous addition of PGE1 or PGE2 and endotoxin enhanced collagenase activity 2- to 10-fold. This increase was detectable at PGE concentrations of 10 nM and was optimal at 0.1-1.0 micrometer. PGF2alpha had little effect on either the enhancement of collagenase production by endotoxin-stimulated macrophages or its restoration in cultures inhibited by indomethacin. Radioimmunoassay of prostaglandins in the culture media revealed that macrophages exposed to endotoxin secreted 40-fold more PGE2 than did unstimulated cells. The increase in PGE2 was detected 4 hr after exposure to endotoxin and was maximal at 14 hr. The peak PGE2 concentrations in the culture media were similar to those of exogenous PGE2 (about 10 nM) needed to restore collagenase production in indomethacin-treated cultures. These findings demonstrate the involvement of PGE in the endotoxin-activation of macrophages with resultant production of collagenase."}
{"id": "PMID:200942", "title": "Sequence arrangement of the 5' ends of simian virus 40 16S and 19S mRNAs.", "content": "Electron microscopic examination of molecular hybrids between simian virus 40 DNA, that had been cleaved with EcoRI and then digested with exonuclease III, and either 16S or 19S mRNA produced late during the viral infection cycle indicated that each of these mRNAs contained a 5'-terminal \"leader\" sequence that was encoded in the viral genome at about map position 0.71-0.75. Hybridization of each of these mRNAs to viral DNA immobilized on nitrocellulose filters supported the electron microscopic observations.", "contents": "Sequence arrangement of the 5' ends of simian virus 40 16S and 19S mRNAs. Electron microscopic examination of molecular hybrids between simian virus 40 DNA, that had been cleaved with EcoRI and then digested with exonuclease III, and either 16S or 19S mRNA produced late during the viral infection cycle indicated that each of these mRNAs contained a 5'-terminal \"leader\" sequence that was encoded in the viral genome at about map position 0.71-0.75. Hybridization of each of these mRNAs to viral DNA immobilized on nitrocellulose filters supported the electron microscopic observations."}
{"id": "PMID:200943", "title": "Complexes of inorganic pyrophosphate, orthophosphate, and calcium as stimulants of 3T3 cell multiplication.", "content": "Addition of 0.1-0.5 mM sodium PP(i) for 17 hr to confluent cultures of BALB/c 3T3 cells in low serum concentrations stimulated the incorporation of [(3)H]thymidine into DNA to an extent equal to that produced by high serum concentration. PP(i) prevented much but not all of the cell detachment that accompanies decreasing the serum concentration of confluent cultures and it increased the saturation density of cultures in high serum concentrations. The stimulation had a sharp concentration dependence and was associated with the appearance in the medium of a flocculent precipitate. Stimulation and precipitate formation were dependent on Ca(2+) and inorganic orthophosphate (HPO(4) (2-)) and were inhibited by Mg(2+). More than half the Ca(2+) requirement could be met with Sr(2+). In the absence of PP(i), supranormal concentrations of either Ca(2+) or HPO(4) (2-) caused graded increases in [(3)H]thymidine incorporation and total cell yield. The effect of supranormal [Ca(2+)] depended on [HPO(4) (2-)] and vice versa, and the Ca(2+) requirement could be partially met by Sr(2+). The stimulation was associated with increasing turbidity of the medium. Various other complexing agents of Ca(2+), including the divalent cation ionophore A 23187, failed to produce stimulation of 3T3 cells. We conclude that water insoluble complexes of PP(i), HPO(4) (2-), and Ca(2+) or, at much higher concentrations, the latter two together, stimulate 3T3 cells and we speculate that this is brought about by the association of these complexes with the cell membrane.", "contents": "Complexes of inorganic pyrophosphate, orthophosphate, and calcium as stimulants of 3T3 cell multiplication. Addition of 0.1-0.5 mM sodium PP(i) for 17 hr to confluent cultures of BALB/c 3T3 cells in low serum concentrations stimulated the incorporation of [(3)H]thymidine into DNA to an extent equal to that produced by high serum concentration. PP(i) prevented much but not all of the cell detachment that accompanies decreasing the serum concentration of confluent cultures and it increased the saturation density of cultures in high serum concentrations. The stimulation had a sharp concentration dependence and was associated with the appearance in the medium of a flocculent precipitate. Stimulation and precipitate formation were dependent on Ca(2+) and inorganic orthophosphate (HPO(4) (2-)) and were inhibited by Mg(2+). More than half the Ca(2+) requirement could be met with Sr(2+). In the absence of PP(i), supranormal concentrations of either Ca(2+) or HPO(4) (2-) caused graded increases in [(3)H]thymidine incorporation and total cell yield. The effect of supranormal [Ca(2+)] depended on [HPO(4) (2-)] and vice versa, and the Ca(2+) requirement could be partially met by Sr(2+). The stimulation was associated with increasing turbidity of the medium. Various other complexing agents of Ca(2+), including the divalent cation ionophore A 23187, failed to produce stimulation of 3T3 cells. We conclude that water insoluble complexes of PP(i), HPO(4) (2-), and Ca(2+) or, at much higher concentrations, the latter two together, stimulate 3T3 cells and we speculate that this is brought about by the association of these complexes with the cell membrane."}
{"id": "PMID:200944", "title": "Hexamethylene bisacetamide induces morphologic changes and increased synthesis of procollagen in cell line from glioblastoma multiforme.", "content": "Addition to hexamethylene bisacetamide (diacetyldiaminohexane) to cultures of a malignant mesenchymal cell line derived from a human glioblastoma multiforme induces morphological changes and stimulates the synthesis of procollagen. The morphological changes include cell elongation, an increase of extracellular material with staining properties of collagen by light microscopy, and an increase in extracellular 220-A fibrils by electron microscopy. The rate of procollagen synthesis increased as much as 20-fold, and the ratio of type I:type III procollagen changed, with type I becoming the predominant form. The change in type I:type III ratio is similar to that seen in the maturation of normal fetal to adult connective tissue.", "contents": "Hexamethylene bisacetamide induces morphologic changes and increased synthesis of procollagen in cell line from glioblastoma multiforme. Addition to hexamethylene bisacetamide (diacetyldiaminohexane) to cultures of a malignant mesenchymal cell line derived from a human glioblastoma multiforme induces morphological changes and stimulates the synthesis of procollagen. The morphological changes include cell elongation, an increase of extracellular material with staining properties of collagen by light microscopy, and an increase in extracellular 220-A fibrils by electron microscopy. The rate of procollagen synthesis increased as much as 20-fold, and the ratio of type I:type III procollagen changed, with type I becoming the predominant form. The change in type I:type III ratio is similar to that seen in the maturation of normal fetal to adult connective tissue."}
{"id": "PMID:200945", "title": "Simian virus 40-specific proteins in the membranes of simian virus 40-transformed hamster and mouse cells.", "content": "Membranes of simian virus 40-transformed hamster lymphocytes and phagocytes, as well as of transformed mouse fibroblasts, contain two classes of antigenic virus-specific protein. The isoelectric points of these proteins, as defined by isoelectric focusing/immune electrophoresis are at pH 4.5 and 4.7. The molecular weights of the pI 4.5 and pI 4.7 components, determined by isoelectric focusing/dodecyl sulfate polyacrylamide electrophoresis, lie near 58,000 and 90,000-110,000, respectively. The pI 4.5 and pI 4.7 proteins are tentatively identified with the surface (transplantation) and U antigens, respectively.", "contents": "Simian virus 40-specific proteins in the membranes of simian virus 40-transformed hamster and mouse cells. Membranes of simian virus 40-transformed hamster lymphocytes and phagocytes, as well as of transformed mouse fibroblasts, contain two classes of antigenic virus-specific protein. The isoelectric points of these proteins, as defined by isoelectric focusing/immune electrophoresis are at pH 4.5 and 4.7. The molecular weights of the pI 4.5 and pI 4.7 components, determined by isoelectric focusing/dodecyl sulfate polyacrylamide electrophoresis, lie near 58,000 and 90,000-110,000, respectively. The pI 4.5 and pI 4.7 proteins are tentatively identified with the surface (transplantation) and U antigens, respectively."}
{"id": "PMID:200946", "title": "Solubilization of apolipoprotein B  and its specific binding by the cellular receptor for low density lipoprotein.", "content": "Low density lipoprotein (LDL) and very low density lipoprotein (VLDL) bind specifically to a receptor on fibroblasts, and it has been postulated that the apoprotein of LDL (apo B) confers the specificity of cellular binding. This hypothesis has been tested in the present study with a watersoluble apo B-bovine serum albumin complex. The binding of (125)I-labeled apo B to cultured fibroblasts was temperature-dependent. Specific binding ranged between 183 and 859 ng/mg of cell protein at a concentration of 5 mug/ml; at 37 degrees , 750-2199 ng/mg was bound and internalized. The binding of apo B greatly exceeded the amount of (125)I-labeled LDL bound at 4 degrees and 37 degrees in the same experiment. Fibroblasts from a subject homozygous for hyper-beta-lipoproteinemia showed minimal binding of (125)I-labeled LDL, consistent with the absence of the cellular LDL receptor. Such cells also had depressed binding of (125)I-labeled apo B. Lymphocytes grown in lipoprotein-deficient medium demonstrated specific binding of LDL; however, freshly isolated lymphocytes did not show such binding. The binding of (125)I-labeled apo B to lymphocytes paralleled the binding of (125)I-labeled LDL. Unlabeled LDL and apo B-albumin complex both competitively inhibited the binding of (125)I-labeled apo B and (125)I-labeled LDL to fibroblasts. When labeled LDL was incubated with fibroblasts for 6 hr at 37 degrees , it underwent cellular internalization and degradation, as measured by the release of (125)I-labeled fragments into the medium. This degradation was inhibited by unlabeled apo B. Conversely, (125)I-labeled apo B also was internalized and degraded by fibroblasts, and this process was inhibited by LDL. These findings demonstrate that apo B binds specifically to the LDL receptor and that the cellular binding of LDL is determined by this apoprotein.", "contents": "Solubilization of apolipoprotein B  and its specific binding by the cellular receptor for low density lipoprotein. Low density lipoprotein (LDL) and very low density lipoprotein (VLDL) bind specifically to a receptor on fibroblasts, and it has been postulated that the apoprotein of LDL (apo B) confers the specificity of cellular binding. This hypothesis has been tested in the present study with a watersoluble apo B-bovine serum albumin complex. The binding of (125)I-labeled apo B to cultured fibroblasts was temperature-dependent. Specific binding ranged between 183 and 859 ng/mg of cell protein at a concentration of 5 mug/ml; at 37 degrees , 750-2199 ng/mg was bound and internalized. The binding of apo B greatly exceeded the amount of (125)I-labeled LDL bound at 4 degrees and 37 degrees in the same experiment. Fibroblasts from a subject homozygous for hyper-beta-lipoproteinemia showed minimal binding of (125)I-labeled LDL, consistent with the absence of the cellular LDL receptor. Such cells also had depressed binding of (125)I-labeled apo B. Lymphocytes grown in lipoprotein-deficient medium demonstrated specific binding of LDL; however, freshly isolated lymphocytes did not show such binding. The binding of (125)I-labeled apo B to lymphocytes paralleled the binding of (125)I-labeled LDL. Unlabeled LDL and apo B-albumin complex both competitively inhibited the binding of (125)I-labeled apo B and (125)I-labeled LDL to fibroblasts. When labeled LDL was incubated with fibroblasts for 6 hr at 37 degrees , it underwent cellular internalization and degradation, as measured by the release of (125)I-labeled fragments into the medium. This degradation was inhibited by unlabeled apo B. Conversely, (125)I-labeled apo B also was internalized and degraded by fibroblasts, and this process was inhibited by LDL. These findings demonstrate that apo B binds specifically to the LDL receptor and that the cellular binding of LDL is determined by this apoprotein."}
{"id": "PMID:200954", "title": "Arterial uptake and synthesis of low density lipoproteins.", "content": "The accumulation of cholesterol in atherosclerotic lesions is associated with an increased uptake of plasma cholesterol and LDL by the arterial wall. During the regression of atherosclerosis, the uptake of these macromolecules returns to or below normal, suggesting that the retention of cholesterol in regressed lesions is due to a defect in the removal of cholesterol from the arterial wall rather than to an abnormality in vascular permeability. Although increased amounts of 125I-LDL were detected in atherosclerotic vessels, the percent distribution and fractional degradation rate of 125I-LDL appeared similar in normal and diseased vessels. The present studies in support of earlier findings in human vessels indicate that LDL in the artery is contained in a number of different cellular and extracellular pools in close association with AMPS. These lipoproteins appeared to be derived not only from the lipoproteins contained in the plasma but also from lipoproteins synthesized by the arterial wall.", "contents": "Arterial uptake and synthesis of low density lipoproteins. The accumulation of cholesterol in atherosclerotic lesions is associated with an increased uptake of plasma cholesterol and LDL by the arterial wall. During the regression of atherosclerosis, the uptake of these macromolecules returns to or below normal, suggesting that the retention of cholesterol in regressed lesions is due to a defect in the removal of cholesterol from the arterial wall rather than to an abnormality in vascular permeability. Although increased amounts of 125I-LDL were detected in atherosclerotic vessels, the percent distribution and fractional degradation rate of 125I-LDL appeared similar in normal and diseased vessels. The present studies in support of earlier findings in human vessels indicate that LDL in the artery is contained in a number of different cellular and extracellular pools in close association with AMPS. These lipoproteins appeared to be derived not only from the lipoproteins contained in the plasma but also from lipoproteins synthesized by the arterial wall."}
{"id": "PMID:200955", "title": "Structural correlates of arterial endothelial permeability in the Evans blue model.", "content": "Normal young pigs were injected intravenously with azo dye Evans blue, which is preferentially and consistently taken up by focal areas in the aorta known to be areas of enhanced permeability. Ferritin was intravenously injected into these animals, and its uptake was quantitated at the electron microscope level at 1, 5 and 15 min after administration. The number of vesicles, large inclusions or vacuoles, and junctions, both labelled and unlabelled, were counted in areas of normal and enhanced permeability. The results have revealed that the number of ferritin grains per vesicle is the same in both areas. However, the percentage of vesicles containing ferritin is significantly higher in areas of enhanced permeability.", "contents": "Structural correlates of arterial endothelial permeability in the Evans blue model. Normal young pigs were injected intravenously with azo dye Evans blue, which is preferentially and consistently taken up by focal areas in the aorta known to be areas of enhanced permeability. Ferritin was intravenously injected into these animals, and its uptake was quantitated at the electron microscope level at 1, 5 and 15 min after administration. The number of vesicles, large inclusions or vacuoles, and junctions, both labelled and unlabelled, were counted in areas of normal and enhanced permeability. The results have revealed that the number of ferritin grains per vesicle is the same in both areas. However, the percentage of vesicles containing ferritin is significantly higher in areas of enhanced permeability."}
{"id": "PMID:200956", "title": "Studies on the passage of plasma proteins across arterial endothelium in relation to atherogenesis.", "content": "Previous studies using isotopically labelled lipoproteins or immuno-histological characterisation of the apolipoproteins present in atherolsclerotic lesions have suggested that lipoproteins varying in size from LDL to VLDL gain entry to the lesions. It has also been shown that a fraction of these lipoproteins is firmly bound to various constituents of the arterial wall. Using the immunoperoxidase technique at the electron microscopic level, it is now confirmed that spherical molecules specifically interacting with labelled anti-LDL (anti-apolipoprotein B) and of a range of molecular diameters corresponding to those of LDL to VLDL are indentifiable in the intersitial matrix of lesions. The labelled antibodies also identified lipoprotein bound to elastin, within smooth muscle cells, and bound to collagen fibres. In advanced lesions lipoprotein was found to be bound not only to \"normal\" (native) collagen fibrils but also with a characteristic periodicity to fibrous long-spacing collagen. The occurrence of this \"abnormal\" form of collagen in plaques is now reported for the first time but its possible significance in relation to atherogenesis is discussed.", "contents": "Studies on the passage of plasma proteins across arterial endothelium in relation to atherogenesis. Previous studies using isotopically labelled lipoproteins or immuno-histological characterisation of the apolipoproteins present in atherolsclerotic lesions have suggested that lipoproteins varying in size from LDL to VLDL gain entry to the lesions. It has also been shown that a fraction of these lipoproteins is firmly bound to various constituents of the arterial wall. Using the immunoperoxidase technique at the electron microscopic level, it is now confirmed that spherical molecules specifically interacting with labelled anti-LDL (anti-apolipoprotein B) and of a range of molecular diameters corresponding to those of LDL to VLDL are indentifiable in the intersitial matrix of lesions. The labelled antibodies also identified lipoprotein bound to elastin, within smooth muscle cells, and bound to collagen fibres. In advanced lesions lipoprotein was found to be bound not only to \"normal\" (native) collagen fibrils but also with a characteristic periodicity to fibrous long-spacing collagen. The occurrence of this \"abnormal\" form of collagen in plaques is now reported for the first time but its possible significance in relation to atherogenesis is discussed."}
{"id": "PMID:200959", "title": "Ultrastructural changes in the lipid inclusions of arterial smooth muscle cells after reduction of high serum cholesterol levels.", "content": "Intimal smooth muscle cells overloaded with lipid droplets can, when the serum cholesterol is reduced to a sufficiently low level over a sufficiently long period, reduce the size of droplets and at least some can completely clear inclusions.", "contents": "Ultrastructural changes in the lipid inclusions of arterial smooth muscle cells after reduction of high serum cholesterol levels. Intimal smooth muscle cells overloaded with lipid droplets can, when the serum cholesterol is reduced to a sufficiently low level over a sufficiently long period, reduce the size of droplets and at least some can completely clear inclusions."}
{"id": "PMID:200960", "title": "Smooth muscle cells of intimal cushions and the localization of atherosclerotic lesions.", "content": "Atherosclerosis results from a precise sequence of endothelial interaction with platelets or thrombocytes and mononuclear cells, uptake of specific lipoproteins, cholesteryl ester removal, production of collagen, elastin ad proteoglycans by activated smooth muscle cells. Thus, both the filtration hypothesis and the thrombogenic hypothesis for the pathogenesis of atherosclerosis appear to be correct.", "contents": "Smooth muscle cells of intimal cushions and the localization of atherosclerotic lesions. Atherosclerosis results from a precise sequence of endothelial interaction with platelets or thrombocytes and mononuclear cells, uptake of specific lipoproteins, cholesteryl ester removal, production of collagen, elastin ad proteoglycans by activated smooth muscle cells. Thus, both the filtration hypothesis and the thrombogenic hypothesis for the pathogenesis of atherosclerosis appear to be correct."}
{"id": "PMID:200962", "title": "Evidence for interactions between central noradrenergic neurons and adrenal hormones in learning and memory.", "content": "The role of ascending noradrenergic projections in the acquisition and retention of a passive avoidance step-down response was evaluated by means of bilateral stereotaxic 6-hydroxydopamine-induced lesions of these systems. Lesions of the dorsal NA bundle alone, or in combination with lesions of the ventral NA bundle, failed to influence either the acquisition or retention of the passive avoidance response. In contrast, animals subjected to dorsal and ventral NA bundle lesions and adrenalectomy exhibited severe deficits in both the acquisition and retention of this response, and this effect was of the same magnitude as was observed after posttrial injections of diethyldithiocarbamate (DDC, 300 mg/kg). Adrenalectomy by itself had a small but significant effect on retention but did not influence acquisition of the response. The results are discussed with reference to the possibility that interactions between adrenal hormones and central NA mechanisms may serve important roles in learning and memory. However, the data provide no support for the hypothesis that central NA neurons are, by themselves, critically involved in these phenomena.", "contents": "Evidence for interactions between central noradrenergic neurons and adrenal hormones in learning and memory. The role of ascending noradrenergic projections in the acquisition and retention of a passive avoidance step-down response was evaluated by means of bilateral stereotaxic 6-hydroxydopamine-induced lesions of these systems. Lesions of the dorsal NA bundle alone, or in combination with lesions of the ventral NA bundle, failed to influence either the acquisition or retention of the passive avoidance response. In contrast, animals subjected to dorsal and ventral NA bundle lesions and adrenalectomy exhibited severe deficits in both the acquisition and retention of this response, and this effect was of the same magnitude as was observed after posttrial injections of diethyldithiocarbamate (DDC, 300 mg/kg). Adrenalectomy by itself had a small but significant effect on retention but did not influence acquisition of the response. The results are discussed with reference to the possibility that interactions between adrenal hormones and central NA mechanisms may serve important roles in learning and memory. However, the data provide no support for the hypothesis that central NA neurons are, by themselves, critically involved in these phenomena."}
{"id": "PMID:200963", "title": "Drugs affecting dopamine neurons and yawning behavior.", "content": "Drugs stimulating the dopamine (DA) neurons in different ways (apomorphine, piribedil, amphetamine, nomifensine, L-DOPA) given in low doses (not producing behavioral excitation) induced yawning in rats. Blockade of DA receptors with neuroleptics counteracted DA-agonists induced yawning which may indicate a dopaminergic component of this behavior.", "contents": "Drugs affecting dopamine neurons and yawning behavior. Drugs stimulating the dopamine (DA) neurons in different ways (apomorphine, piribedil, amphetamine, nomifensine, L-DOPA) given in low doses (not producing behavioral excitation) induced yawning in rats. Blockade of DA receptors with neuroleptics counteracted DA-agonists induced yawning which may indicate a dopaminergic component of this behavior."}
{"id": "PMID:200966", "title": "Effect of elevated brain GABA concentrations on the actions of bicuculline and picrotoxin in mice.", "content": "gamma-Acetylenic GABA and gamma-vinyl GABA, two catalytic irreversible inhibitors of mammalian brain GABA transaminase that produce several-fold increases in brain GABA concentrations were tested for their effects on bicuculline and picrotoxin-induced seizures and mortality in mice. Neither inhibitor influenced the frequency of seizures or death produced by either bicuculline or picrotoxin. Both inhibitors, however, produced a dose-dependent prolongation of the time to onset of seizures and death induced by picrotoxin but by bicuculline. These results suggest differences in the antagonism by bicuculline and picrotoxin of GABA-mediated neural functions.", "contents": "Effect of elevated brain GABA concentrations on the actions of bicuculline and picrotoxin in mice. gamma-Acetylenic GABA and gamma-vinyl GABA, two catalytic irreversible inhibitors of mammalian brain GABA transaminase that produce several-fold increases in brain GABA concentrations were tested for their effects on bicuculline and picrotoxin-induced seizures and mortality in mice. Neither inhibitor influenced the frequency of seizures or death produced by either bicuculline or picrotoxin. Both inhibitors, however, produced a dose-dependent prolongation of the time to onset of seizures and death induced by picrotoxin but by bicuculline. These results suggest differences in the antagonism by bicuculline and picrotoxin of GABA-mediated neural functions."}
{"id": "PMID:200967", "title": "Stimulus effects of delta(9)-THC and its interaction with naltrexone and catecholamine blockers in rats.", "content": "Rats trained in a T-shaped maze to discriminate the effects of i.p. injections of delta(9)-tetrahydrocannabinol (delta(9)-THC, 4 mg/kg) and the effects of the vehicle were tested for antagonism and generalization to the delta(9)-THC stimulus by naltrexone (4 mg/kg), haloperidol (0.32 mg/kg), propranolol (20 mg/kg), and phenoxybenzamine (10 mg/kg). None of these drugs blocked the delta(9)-THC stimulus, nor were they found to generalize to delta(9)-THC.", "contents": "Stimulus effects of delta(9)-THC and its interaction with naltrexone and catecholamine blockers in rats. Rats trained in a T-shaped maze to discriminate the effects of i.p. injections of delta(9)-tetrahydrocannabinol (delta(9)-THC, 4 mg/kg) and the effects of the vehicle were tested for antagonism and generalization to the delta(9)-THC stimulus by naltrexone (4 mg/kg), haloperidol (0.32 mg/kg), propranolol (20 mg/kg), and phenoxybenzamine (10 mg/kg). None of these drugs blocked the delta(9)-THC stimulus, nor were they found to generalize to delta(9)-THC."}
{"id": "PMID:200964", "title": "[A case of varices caused by angiodysplasia of the upper limb].", "content": "The authors recall that the syndrome of Klippel and Trenaunay, which in its typical form most commonly involves a lower limb, constitutes the best known example of the angiodysplastic disorders, and go on to describe the case of a patient with extensive congenital varicose veins of the left upper limb, with slight bone hypertrophy and changes in the limb skeleton. In the varicose veins were numerous phleboliths, and phlebography revealed agenesis of the deep veins of the forearm. In discussion they try to demonstrate the diagnostic difficulties of this disorder which may suggest a phlebo-angiomatosis, a \"pure\" phlebodysplasia or an atypical Klippel and Trenaunay syndrome.", "contents": "[A case of varices caused by angiodysplasia of the upper limb]. The authors recall that the syndrome of Klippel and Trenaunay, which in its typical form most commonly involves a lower limb, constitutes the best known example of the angiodysplastic disorders, and go on to describe the case of a patient with extensive congenital varicose veins of the left upper limb, with slight bone hypertrophy and changes in the limb skeleton. In the varicose veins were numerous phleboliths, and phlebography revealed agenesis of the deep veins of the forearm. In discussion they try to demonstrate the diagnostic difficulties of this disorder which may suggest a phlebo-angiomatosis, a \"pure\" phlebodysplasia or an atypical Klippel and Trenaunay syndrome."}
{"id": "PMID:200969", "title": "Computed tomographic demonstration of hepatic tumor with the aid of intravenous iodinated fat emulsion. An experimental study.", "content": "Computed tomography showed improved visualization of carcinogen-induced hepatoma in monkeys following intravenous injection of an experimental contrast material AG 60-99; selective opacification of the liver and spleen was accomplished with a dose of greater than or equal to 0.1 ml/kg, a fraction of the dose used in conventional x-ray tomography. This marked reduction was made possible by the improved density resolution of the CT scanner. This may be the first organ-specific contrast material intended primarily for use with CT scanners.", "contents": "Computed tomographic demonstration of hepatic tumor with the aid of intravenous iodinated fat emulsion. An experimental study. Computed tomography showed improved visualization of carcinogen-induced hepatoma in monkeys following intravenous injection of an experimental contrast material AG 60-99; selective opacification of the liver and spleen was accomplished with a dose of greater than or equal to 0.1 ml/kg, a fraction of the dose used in conventional x-ray tomography. This marked reduction was made possible by the improved density resolution of the CT scanner. This may be the first organ-specific contrast material intended primarily for use with CT scanners."}
{"id": "PMID:200968", "title": "Comparison of laboratory performance with blind and mail-distributed proficiency testing samples.", "content": "Simulated addict urine samples containing drugs were sent to collaborating hospital administrators and officials of methadone centers, who then forwarded the samples to their supporting laboratories as though they were ordinary specimens from patients. The laboratories, which were already participating in the proficiency testing program of the Center for Disease Control, received the identical test samples in the mail as part of a regular Center for Disease Control proficiency testing program. Most of the laboratories performed acceptably with the mail-distributed samples, but many performed poorly when the identical samples were sent to them as if they were specimens from patients. Because of the limitations of proficiency testing involving mail-distribution samples and the impracticality of extensive testing with blind samples on a national level, the Center for Disease Control proposes to compliment its regular proficiency testing program with a monitored, onsite program of performance evaluation.", "contents": "Comparison of laboratory performance with blind and mail-distributed proficiency testing samples. Simulated addict urine samples containing drugs were sent to collaborating hospital administrators and officials of methadone centers, who then forwarded the samples to their supporting laboratories as though they were ordinary specimens from patients. The laboratories, which were already participating in the proficiency testing program of the Center for Disease Control, received the identical test samples in the mail as part of a regular Center for Disease Control proficiency testing program. Most of the laboratories performed acceptably with the mail-distributed samples, but many performed poorly when the identical samples were sent to them as if they were specimens from patients. Because of the limitations of proficiency testing involving mail-distribution samples and the impracticality of extensive testing with blind samples on a national level, the Center for Disease Control proposes to compliment its regular proficiency testing program with a monitored, onsite program of performance evaluation."}
{"id": "PMID:200983", "title": "Viral attributes and host factors in carcinogenesis: herpesviruses.", "content": "This paper describes two different experiments of nature: 1) the persistence of unusual virus strains of Epstein-Barr virus (EBV) (which proved oncogenic in vitro) and cytomegalovirus (CMV) in lymphoid cells following congenital or early acquired infection; 2) the occurence of multiple cases of Burkitt's lymphoma and nasopharyngeal carcinoma in one family. All the members of this family were EBV viral capsid antigen (VCA) and nuclear antigen (EBNA) antibody positive. The two patients with nasopharyngeal carcinoma had high titers of EBV-VCA, EA, and EBNA antibodies. The only member of this family having EBV early antigen (EA antibodies in addition to the patients with tumors was the mother. Borderline IgA deficiency was documented in 3 members of this family. These findings illustrate the importance of host factors (intracellular resistance to transformation and secondarily, immunological surveillance) in the outcome of the host-virus challenge whether cancer or infectious disease is the outcome. Extensive studies of these cases may provide the best insight into the mysteries of viral oncogenesis.", "contents": "Viral attributes and host factors in carcinogenesis: herpesviruses. This paper describes two different experiments of nature: 1) the persistence of unusual virus strains of Epstein-Barr virus (EBV) (which proved oncogenic in vitro) and cytomegalovirus (CMV) in lymphoid cells following congenital or early acquired infection; 2) the occurence of multiple cases of Burkitt's lymphoma and nasopharyngeal carcinoma in one family. All the members of this family were EBV viral capsid antigen (VCA) and nuclear antigen (EBNA) antibody positive. The two patients with nasopharyngeal carcinoma had high titers of EBV-VCA, EA, and EBNA antibodies. The only member of this family having EBV early antigen (EA antibodies in addition to the patients with tumors was the mother. Borderline IgA deficiency was documented in 3 members of this family. These findings illustrate the importance of host factors (intracellular resistance to transformation and secondarily, immunological surveillance) in the outcome of the host-virus challenge whether cancer or infectious disease is the outcome. Extensive studies of these cases may provide the best insight into the mysteries of viral oncogenesis."}
{"id": "PMID:200985", "title": "Retinal structure in Synbranchus marmoratus with observations on two new cone myoid inclusions.", "content": "The retina of a South American swamp eel, Synbranchus marmoratus (Synbranchidae), was studied by Golgi impregnation, light and electron microscopy. Its principal features include (1) the presence of a dense matrix, possibly a new type of tapetum lucidum, in the pigment epithelium, (2) a well developed photoreceptor layer containing large rods, single, double and triple cones, and (3) well developped inner nuclear and plexiform layers, with the exception of horizontal cells which are few and relatively small. These and other observations are discussed in relation to the photic environment and habits of this fish. The presence of microfilament bundles and two unusual features, microtubuleladen dense bodies and paracrystalline inclusions, in cone myoids are discussed in terms of their possible involvement in retinomotor responses.", "contents": "Retinal structure in Synbranchus marmoratus with observations on two new cone myoid inclusions. The retina of a South American swamp eel, Synbranchus marmoratus (Synbranchidae), was studied by Golgi impregnation, light and electron microscopy. Its principal features include (1) the presence of a dense matrix, possibly a new type of tapetum lucidum, in the pigment epithelium, (2) a well developed photoreceptor layer containing large rods, single, double and triple cones, and (3) well developped inner nuclear and plexiform layers, with the exception of horizontal cells which are few and relatively small. These and other observations are discussed in relation to the photic environment and habits of this fish. The presence of microfilament bundles and two unusual features, microtubuleladen dense bodies and paracrystalline inclusions, in cone myoids are discussed in terms of their possible involvement in retinomotor responses."}
{"id": "PMID:200987", "title": "[Comparison between two types of pertussis vaccines].", "content": "We have produced pertussis vaccines with laboratory and industrial methods. The characteristic of laboratory cultivation of microorganisms is, in this context, growth on Hornibrook medium in low form flask and in stationary culture. Industrial cultivation is done in homogenous culture on a B-2 medium in fermentor. The strains utilized were isolated from whooping-cough cases in the Montreal region. The yield (org. x 10(9)/ml) obtained with an industrial cultivation of B. pertussis was 4 to 7 times higher than that reached with a laboratory cultivation of this microorganism. The non-toxicity as expressed in weight gain of mice was shown for both types of vaccine. The vaccines produced in fermentor were less histamino sensibilizing for mice than the one produced in stationary flash culture. The quality of the vaccines achieved by industrial method is easily reproducible due to the fact that enough variables can be measured.", "contents": "[Comparison between two types of pertussis vaccines]. We have produced pertussis vaccines with laboratory and industrial methods. The characteristic of laboratory cultivation of microorganisms is, in this context, growth on Hornibrook medium in low form flask and in stationary culture. Industrial cultivation is done in homogenous culture on a B-2 medium in fermentor. The strains utilized were isolated from whooping-cough cases in the Montreal region. The yield (org. x 10(9)/ml) obtained with an industrial cultivation of B. pertussis was 4 to 7 times higher than that reached with a laboratory cultivation of this microorganism. The non-toxicity as expressed in weight gain of mice was shown for both types of vaccine. The vaccines produced in fermentor were less histamino sensibilizing for mice than the one produced in stationary flash culture. The quality of the vaccines achieved by industrial method is easily reproducible due to the fact that enough variables can be measured."}
{"id": "PMID:200989", "title": "[Pharmacological suppression of paradoxical sleep in the newborn rat (author's transl)].", "content": "In an attempt to suppress paradoxical sleep (PS) an intracerebral injection of 6 0HDA was carried out on rat faetuses at a gestational age of 16-20 days. In these animals a delay in maturation occurred compared to controls, the only modification of sleep being observed however, related to the circadian rhythmn of PS. The possible reasons for this are discussed within the framework of a concept relating paradoxical sleep to cerebral maturation.", "contents": "[Pharmacological suppression of paradoxical sleep in the newborn rat (author's transl)]. In an attempt to suppress paradoxical sleep (PS) an intracerebral injection of 6 0HDA was carried out on rat faetuses at a gestational age of 16-20 days. In these animals a delay in maturation occurred compared to controls, the only modification of sleep being observed however, related to the circadian rhythmn of PS. The possible reasons for this are discussed within the framework of a concept relating paradoxical sleep to cerebral maturation."}
{"id": "PMID:200993", "title": "Comparisons of antidotal efficacy of sodium diethyldithiocarbamate, D-penicillamine and triethylenetetramine upon acute toxicity of nickel carbonyl in rats.", "content": "Sodium diethyldithiocarbamate, D-penicillamine, and triethylene-tetramine were administered to rats by im injection in dosages equivalent to 0.6 times their respective LD50 values in order to compare their relative effectiveness in prevention of death caused by exposure for 15 min to inhalation of nickel carbonyl (1.4 or 4.2 mg Ni (CO)4/liter of air). When the three drugs were administered to groups of rats at 10 min before or after the exposure to nickel carbonyl, sodium diethyldithiocarbamate was the most effective antidote. In contrast, then the drugs were administered at 6 hr after exposure to nickel carbonyl, D-penicillamine was the most effective antidote. Based upon the combined results of 4 sets of experiments, sodium diethyldithiocarbamate and D-penicillamine were significantly more effective than triethylenetetramine. The authors recommend that sodium diethyldithio-carbamate should remain the chelating agent of choice for therapy of nickel carbonyl poisoning. If sodium diethyldithiocarbamate is not available or if its use is contraindicated, D-penicillamine might be considered as an alternative chelating agent.", "contents": "Comparisons of antidotal efficacy of sodium diethyldithiocarbamate, D-penicillamine and triethylenetetramine upon acute toxicity of nickel carbonyl in rats. Sodium diethyldithiocarbamate, D-penicillamine, and triethylene-tetramine were administered to rats by im injection in dosages equivalent to 0.6 times their respective LD50 values in order to compare their relative effectiveness in prevention of death caused by exposure for 15 min to inhalation of nickel carbonyl (1.4 or 4.2 mg Ni (CO)4/liter of air). When the three drugs were administered to groups of rats at 10 min before or after the exposure to nickel carbonyl, sodium diethyldithiocarbamate was the most effective antidote. In contrast, then the drugs were administered at 6 hr after exposure to nickel carbonyl, D-penicillamine was the most effective antidote. Based upon the combined results of 4 sets of experiments, sodium diethyldithiocarbamate and D-penicillamine were significantly more effective than triethylenetetramine. The authors recommend that sodium diethyldithio-carbamate should remain the chelating agent of choice for therapy of nickel carbonyl poisoning. If sodium diethyldithiocarbamate is not available or if its use is contraindicated, D-penicillamine might be considered as an alternative chelating agent."}
{"id": "PMID:200994", "title": "Angiotensinase activity in red blood cell membranes and intact adrenal cells.", "content": "The present study was undertaken to characterize angiotensinase activity in human red blood cells (RBCs), RBC ghosts and rabbit adrenal cells. It was found, by the use of paper chromatography, that each of these preparations possess enzymes capable of converting angiotensin II to its heptapeptide derivative, [des=Asp1] angiotensin II (angiotensin III). Further characterization of these enzymes by the use of a chromogenic assay indicates that although intact RBCs do not split sarcosine-beta-naphthylamide, RBC ghosts do. Intact rabbit adrenal cells from the zona glomerulosa, however, do show activity against sarcosine-beta-naphthylamide. This is interpreted to indicate the presence of non-specific angiotensinases on the inside of the RBC membrane and the outside of the adrenal cell membrane.", "contents": "Angiotensinase activity in red blood cell membranes and intact adrenal cells. The present study was undertaken to characterize angiotensinase activity in human red blood cells (RBCs), RBC ghosts and rabbit adrenal cells. It was found, by the use of paper chromatography, that each of these preparations possess enzymes capable of converting angiotensin II to its heptapeptide derivative, [des=Asp1] angiotensin II (angiotensin III). Further characterization of these enzymes by the use of a chromogenic assay indicates that although intact RBCs do not split sarcosine-beta-naphthylamide, RBC ghosts do. Intact rabbit adrenal cells from the zona glomerulosa, however, do show activity against sarcosine-beta-naphthylamide. This is interpreted to indicate the presence of non-specific angiotensinases on the inside of the RBC membrane and the outside of the adrenal cell membrane."}
{"id": "PMID:200990", "title": "[The normal E.E.G. of the neonate (author's transl)].", "content": "This study is the statement of the present knowledge of the normal EEG activity of the full term and the premature neonates. The criteria for normality of the records are based on transversal studies of normal newborn babies, born after a normal pregnancy and a normal delivery (Apgar 9 and 10). Follow up studies of children over of period of 3 years or more have allowed to appreciate the variability of the neonatal EEG, especially in premature babies having a later normal psycho-motor development. The variability of bioelectric activity is considerable from child to child and in the same child from one moment to another especially during quiet sleep. EEG activity varies according to the states of vigilance and sleep. Organisation of sleep is independent of the recording methods, as shown by a comparative study using different technics of electrode application.", "contents": "[The normal E.E.G. of the neonate (author's transl)]. This study is the statement of the present knowledge of the normal EEG activity of the full term and the premature neonates. The criteria for normality of the records are based on transversal studies of normal newborn babies, born after a normal pregnancy and a normal delivery (Apgar 9 and 10). Follow up studies of children over of period of 3 years or more have allowed to appreciate the variability of the neonatal EEG, especially in premature babies having a later normal psycho-motor development. The variability of bioelectric activity is considerable from child to child and in the same child from one moment to another especially during quiet sleep. EEG activity varies according to the states of vigilance and sleep. Organisation of sleep is independent of the recording methods, as shown by a comparative study using different technics of electrode application."}
{"id": "PMID:200995", "title": "Cyclic AMP-dependent protein kinase activation in hearts from euthyroid and hyperthyroid rats.", "content": "The degree of cyclic AMP-dependent protein kinase activation in response to dibutyryl cyclic AMP and norepinephrine was determined in samples of rat heart obtained from hyperthyroid and euthyroid animals. The data indicate that thyroid hormone-induced supersensitivity to the metabolic effects of the catecholamines cannot be explained on the basis of a change in activity of supernatant protein kinase.", "contents": "Cyclic AMP-dependent protein kinase activation in hearts from euthyroid and hyperthyroid rats. The degree of cyclic AMP-dependent protein kinase activation in response to dibutyryl cyclic AMP and norepinephrine was determined in samples of rat heart obtained from hyperthyroid and euthyroid animals. The data indicate that thyroid hormone-induced supersensitivity to the metabolic effects of the catecholamines cannot be explained on the basis of a change in activity of supernatant protein kinase."}
{"id": "PMID:200991", "title": "[Normal children sleep E.E.Gs from 5 months to 3 years old (author's transl)].", "content": "The sleep E.E.G. of the child under 3 years old is characteristic from several points of view: Drowsiness: The hypersynchrony is always observed. It is more continuous in younger children, than in the older one, where only bursts of hypersynchrony are seen. The fast rhythms of low amplitude may exist, during stage 2 sleep, but they are rare. Calm Sleep (C.S.): The vertex humps are more and more acute and sharper from 18 months. The sleep spindles are of high amplitude and frequent at 6 and 8 months. They diminish later. It may be for that reason that III and IV sleep stages seem to be more important after 12 months than before. From 21 months, we have observed an unusual pattern during C.S.: rhythmic and diffuse th\u00eata rhythms of about 6 c/s. Paradoxal sleep (P.S.): If it is possible to observe P.S. during day-naps 8 or 9 months, it is rare later and for recording P.S., it is necessary to record E.E.G.s at night. The E.E.Gs are either a little like stage I E.E.G, or consistent of high and monomorphic delta waves. If it is possible to observe at least 3 complete sleep cycles, the proportion of P.S. is about 20 p. 100 of the total length of the sleep. At least, it is very important, even in medical practice, to record not only E.E.G. but also polygraphic leads: breathing, electro-myogram, electrocardiogram, and to notice also the rapid eyes movements.", "contents": "[Normal children sleep E.E.Gs from 5 months to 3 years old (author's transl)]. The sleep E.E.G. of the child under 3 years old is characteristic from several points of view: Drowsiness: The hypersynchrony is always observed. It is more continuous in younger children, than in the older one, where only bursts of hypersynchrony are seen. The fast rhythms of low amplitude may exist, during stage 2 sleep, but they are rare. Calm Sleep (C.S.): The vertex humps are more and more acute and sharper from 18 months. The sleep spindles are of high amplitude and frequent at 6 and 8 months. They diminish later. It may be for that reason that III and IV sleep stages seem to be more important after 12 months than before. From 21 months, we have observed an unusual pattern during C.S.: rhythmic and diffuse th\u00eata rhythms of about 6 c/s. Paradoxal sleep (P.S.): If it is possible to observe P.S. during day-naps 8 or 9 months, it is rare later and for recording P.S., it is necessary to record E.E.G.s at night. The E.E.Gs are either a little like stage I E.E.G, or consistent of high and monomorphic delta waves. If it is possible to observe at least 3 complete sleep cycles, the proportion of P.S. is about 20 p. 100 of the total length of the sleep. At least, it is very important, even in medical practice, to record not only E.E.G. but also polygraphic leads: breathing, electro-myogram, electrocardiogram, and to notice also the rapid eyes movements."}
{"id": "PMID:200996", "title": "Human fat cell adenylate cyclase. Modulation of parathyroid hormone action by guanine nucleotides.", "content": "The effects of guanine nucleotides on basal and parathyroid hormone-stimulated adenylate cyclase of human fat cell ghosts were studied. GTP (10(-7)-10(-3) M) caused a dose-dependent inhibition of basal enzyme activity, but it had no significant effect on PTH-stimulated rates of cAMP-formation. The guanine nucleotide analogue 5'-guanylyl-imidodiphosphate GMP (PNP) when applied in the same concentration range, stimulated basal as well as PTH-activated adenylate cyclase activity up to 300%. GMP (PNP) activation was non-linear with time. PTH-activated the human fat cell adenylate cyclase via an individual receptor distinct from beta-adrenergic receptor sites.", "contents": "Human fat cell adenylate cyclase. Modulation of parathyroid hormone action by guanine nucleotides. The effects of guanine nucleotides on basal and parathyroid hormone-stimulated adenylate cyclase of human fat cell ghosts were studied. GTP (10(-7)-10(-3) M) caused a dose-dependent inhibition of basal enzyme activity, but it had no significant effect on PTH-stimulated rates of cAMP-formation. The guanine nucleotide analogue 5'-guanylyl-imidodiphosphate GMP (PNP) when applied in the same concentration range, stimulated basal as well as PTH-activated adenylate cyclase activity up to 300%. GMP (PNP) activation was non-linear with time. PTH-activated the human fat cell adenylate cyclase via an individual receptor distinct from beta-adrenergic receptor sites."}
{"id": "PMID:200997", "title": "The occurrence of antibody to Babesia and to the virus of louping-ill in deer in Scotland.", "content": "Sera of wild red deer from 16 localities in Scotland were tested by the indirect fluorescent antibody technique for antibody to Babesia and by the haemagglutination inhibition test for antibody to the virus of louping-ill. Babesial antibody was detected in sera from all localities in proportions ranging from 22 to 100 per cent. Antibody to louping-ill virus could not be demonstrated in sera from five of the localities and in the other 11 was found less frequently than was antibody to Babesia. Sera from male and female deer were positive for louping-ill in almost equal proportions whereas the incidence of babesial antibody was significantly lower in females than in mature males. This difference could be explained by the habits of the deer. The variable occurrence of louping-ill antibody suggested that red deer are tangential hosts for the virus.", "contents": "The occurrence of antibody to Babesia and to the virus of louping-ill in deer in Scotland. Sera of wild red deer from 16 localities in Scotland were tested by the indirect fluorescent antibody technique for antibody to Babesia and by the haemagglutination inhibition test for antibody to the virus of louping-ill. Babesial antibody was detected in sera from all localities in proportions ranging from 22 to 100 per cent. Antibody to louping-ill virus could not be demonstrated in sera from five of the localities and in the other 11 was found less frequently than was antibody to Babesia. Sera from male and female deer were positive for louping-ill in almost equal proportions whereas the incidence of babesial antibody was significantly lower in females than in mature males. This difference could be explained by the habits of the deer. The variable occurrence of louping-ill antibody suggested that red deer are tangential hosts for the virus."}
{"id": "PMID:200999", "title": "Identification of the receptor involved in adrenaline mediated sweating in the horse.", "content": "Using adrenergic agonists and antagonists this study has demonstrated that adrenaline induced sweating is mediated via beta2-adrenoreceptors in the horse.", "contents": "Identification of the receptor involved in adrenaline mediated sweating in the horse. Using adrenergic agonists and antagonists this study has demonstrated that adrenaline induced sweating is mediated via beta2-adrenoreceptors in the horse."}
{"id": "PMID:201000", "title": "Phosphatase activity of placental extracts and pregnant mare's plasma.", "content": "Equine placental extracts show phosphatase activity with a pH optimum between 4.5 and 6. The enzyme shows heat stability to 45 degrees C and electrophoresis on cellulose acetate demonstrates the presence of two bands of activity. Histochemistry confirms the presence of phosphatase activity in the placental villi. Assay of plasma samples from pregnant mares showed no increase in phosphatase activity through pregnancy under conditions of test.", "contents": "Phosphatase activity of placental extracts and pregnant mare's plasma. Equine placental extracts show phosphatase activity with a pH optimum between 4.5 and 6. The enzyme shows heat stability to 45 degrees C and electrophoresis on cellulose acetate demonstrates the presence of two bands of activity. Histochemistry confirms the presence of phosphatase activity in the placental villi. Assay of plasma samples from pregnant mares showed no increase in phosphatase activity through pregnancy under conditions of test."}
{"id": "PMID:201003", "title": "[Meningitis caused by enteroviruses. Clinical and virological study of several sporadic cases in adults].", "content": "In the course of seven years (1968--1974) viral investigations were carried out in 212 casese of meningitis; predominantly Coxsackie viruses and sometimes ECHO viruses were isolated from 80 cases (37.73%). No polioviruses were isolated. Analysis of the clinical data (onset, general conidtion, evolution, complications, psychical, renal and cardiac disturbances etc.) revealed the severe aspect of these cases. The aspect and evolution of the cerebrospinal fluid showed the presence in almost 25% of the cases of an increased number of cellular elements of more than 1 000/mm3 and albumin sometimes far above normal values with a slow return (3--4 weeks). The complex therapy applied in more than half the cases demonstrates the necessity of attentive follow up of these cases of viral meningitis.", "contents": "[Meningitis caused by enteroviruses. Clinical and virological study of several sporadic cases in adults]. In the course of seven years (1968--1974) viral investigations were carried out in 212 casese of meningitis; predominantly Coxsackie viruses and sometimes ECHO viruses were isolated from 80 cases (37.73%). No polioviruses were isolated. Analysis of the clinical data (onset, general conidtion, evolution, complications, psychical, renal and cardiac disturbances etc.) revealed the severe aspect of these cases. The aspect and evolution of the cerebrospinal fluid showed the presence in almost 25% of the cases of an increased number of cellular elements of more than 1 000/mm3 and albumin sometimes far above normal values with a slow return (3--4 weeks). The complex therapy applied in more than half the cases demonstrates the necessity of attentive follow up of these cases of viral meningitis."}
{"id": "PMID:201006", "title": "[Quantitative evaluation of the dynamics of tubercular mediastinal adenopathy treated with rifampicin and ethambutol].", "content": "The authors have followed for one year the rhythm of involution of adenopathy in 114 patients aged between 0 and 16 years, with patent primary infection, in which four therapeutic regimens have been randomly applied, in continuous or intermittent administration, with INH-RMP; RMP-EMB; INH-EMB; INH-SM. Quantified data were obtained with the aid of a planimeter, measuring the surface of the adenopathy on trimestrial seriotomographies. The rhythm of involution was evaluated by the variable halving time of the surface of the adenopathy under treatment. The percentage, the data of the physical model, showed that in the first 3--4 months, detection of the curves is more rapid for RMP and the 7/7 formula, but with almost similar results (8--14%) at 12 months. By processing the data in the computer, depending on the mathematical model, it was estimated that the halving time is by 90,4 days shorter for RMP and similar for EMB and SM.", "contents": "[Quantitative evaluation of the dynamics of tubercular mediastinal adenopathy treated with rifampicin and ethambutol]. The authors have followed for one year the rhythm of involution of adenopathy in 114 patients aged between 0 and 16 years, with patent primary infection, in which four therapeutic regimens have been randomly applied, in continuous or intermittent administration, with INH-RMP; RMP-EMB; INH-EMB; INH-SM. Quantified data were obtained with the aid of a planimeter, measuring the surface of the adenopathy on trimestrial seriotomographies. The rhythm of involution was evaluated by the variable halving time of the surface of the adenopathy under treatment. The percentage, the data of the physical model, showed that in the first 3--4 months, detection of the curves is more rapid for RMP and the 7/7 formula, but with almost similar results (8--14%) at 12 months. By processing the data in the computer, depending on the mathematical model, it was estimated that the halving time is by 90,4 days shorter for RMP and similar for EMB and SM."}
{"id": "PMID:201007", "title": "[Clinical, radiological and bacteriological study of pulmonary tuberculosis with bacteria showing drug resistance].", "content": "The authors have investigated two groups of patients of young age suffering from tuberculosis with germs showing primary resistance to chemotherapeutic agents (61 cases), and with germs displaying sensitivity to these agents (64 cases). The following conclusions have been reached: tuberculosis with germs showing primary drug resistance did not display onset modalities, clinically and radiologically, that differed significantly from other types of tuberculosis; sputum conversion is more slow in patients with resistant germs than in those with sensitive germs in the first two months of treatment, but following application of the treatment according to the data resulting from the antibiogram, this differences quickly disappeared. The presence of a smaller number of complete recoveries and of a surplus of doubtful recoveries can be explained in the same way in this group of patients: the final results are similar in both groups of patients, evidencing that the treatment of pulmonary tuberculosis due to germs showing parimary drug resistance does not give rise to particular problems.", "contents": "[Clinical, radiological and bacteriological study of pulmonary tuberculosis with bacteria showing drug resistance]. The authors have investigated two groups of patients of young age suffering from tuberculosis with germs showing primary resistance to chemotherapeutic agents (61 cases), and with germs displaying sensitivity to these agents (64 cases). The following conclusions have been reached: tuberculosis with germs showing primary drug resistance did not display onset modalities, clinically and radiologically, that differed significantly from other types of tuberculosis; sputum conversion is more slow in patients with resistant germs than in those with sensitive germs in the first two months of treatment, but following application of the treatment according to the data resulting from the antibiogram, this differences quickly disappeared. The presence of a smaller number of complete recoveries and of a surplus of doubtful recoveries can be explained in the same way in this group of patients: the final results are similar in both groups of patients, evidencing that the treatment of pulmonary tuberculosis due to germs showing parimary drug resistance does not give rise to particular problems."}
{"id": "PMID:201008", "title": "[Bronchopulmonary carcinosarcomas. Therapeutic indications].", "content": "The authors make an analysis of 11 cases of carcinosarcoma that have underwent surgery in the Clinic of Thoracic Surgery. The authors stress the rarity of these cases in their statistics. Only 11 carcinosarcomas have been identified out of a total of 2.500 cases of bronchopulmonary tumors operated in the Clinic. The difficulty of pre-operatory diagnosis is also stressed. Indications for surgical treatment are mandatory in all cases, even when the expected effects are palliative.", "contents": "[Bronchopulmonary carcinosarcomas. Therapeutic indications]. The authors make an analysis of 11 cases of carcinosarcoma that have underwent surgery in the Clinic of Thoracic Surgery. The authors stress the rarity of these cases in their statistics. Only 11 carcinosarcomas have been identified out of a total of 2.500 cases of bronchopulmonary tumors operated in the Clinic. The difficulty of pre-operatory diagnosis is also stressed. Indications for surgical treatment are mandatory in all cases, even when the expected effects are palliative."}
{"id": "PMID:201009", "title": "[Prevalence of chronic productive cough and obstructive ventilatory dysfunction in a rural community with minimal air pollution].", "content": "Results obtained during an epidemiological investigation on chronic cough and obstructive ventilatory dysfunction in subjects without bronchopulmonary affections of known etiopathogeny, carried out in a rural environment with minimal air pollution on 282 men aged between 40 and 69 years, indicate the following: --there was a lower prevalence of chronic cough in the rural environment as compared with the urban one (12.8:21.0). The percentage of heavy smokers being approximately similar in both environments, the difference could be explained by the variable intensity of air pollution, the impact of which was exerted on the large airways (hypertrophy of the serous-mucous glands resulting in hypercrinia with dyscrinia); --similar prevalence in the two environments of the obstructive ventilatory dysfunction (11,0:8,7) suggests that this abnormality, an expression of the narrowing of the small airways, could be due to other pathogenic factors. Functional pulmonary tests with sensitivity higher than the ratio between FEV 1.0 and VC (as, for instance VEmx 50% VC) could provide higher percentages of obstructive disturbances both among chronic coughing and non-coughing subjects, revealing the latent form of the obstruction, as opposed to the manifest one as evidenced by a decrease of the FEV 1.0/VC ratio.", "contents": "[Prevalence of chronic productive cough and obstructive ventilatory dysfunction in a rural community with minimal air pollution]. Results obtained during an epidemiological investigation on chronic cough and obstructive ventilatory dysfunction in subjects without bronchopulmonary affections of known etiopathogeny, carried out in a rural environment with minimal air pollution on 282 men aged between 40 and 69 years, indicate the following: --there was a lower prevalence of chronic cough in the rural environment as compared with the urban one (12.8:21.0). The percentage of heavy smokers being approximately similar in both environments, the difference could be explained by the variable intensity of air pollution, the impact of which was exerted on the large airways (hypertrophy of the serous-mucous glands resulting in hypercrinia with dyscrinia); --similar prevalence in the two environments of the obstructive ventilatory dysfunction (11,0:8,7) suggests that this abnormality, an expression of the narrowing of the small airways, could be due to other pathogenic factors. Functional pulmonary tests with sensitivity higher than the ratio between FEV 1.0 and VC (as, for instance VEmx 50% VC) could provide higher percentages of obstructive disturbances both among chronic coughing and non-coughing subjects, revealing the latent form of the obstruction, as opposed to the manifest one as evidenced by a decrease of the FEV 1.0/VC ratio."}
{"id": "PMID:201010", "title": "[Correlations between culture methods, double diffusion and immunofluorescence in the laboratory diagnosis of mycoses (candidiasis and aspergillosis)].", "content": "Of a total of 1950 patients with various pneumologic affections 115 cases were selected, on the basis of positive mycologic results on examination of the bronchial aspirate. In these patients immunodiffusion and immunofluorescence serological tests were carried out. Confrontation with the clinical and histopathologic diagnosis showed that the simultaneous use of mycological studies (of the bronchial aspirate) and of complex serologic investigations (immunodiffusion, immunofluorescence) allow to make a correcs and aspergilloses.", "contents": "[Correlations between culture methods, double diffusion and immunofluorescence in the laboratory diagnosis of mycoses (candidiasis and aspergillosis)]. Of a total of 1950 patients with various pneumologic affections 115 cases were selected, on the basis of positive mycologic results on examination of the bronchial aspirate. In these patients immunodiffusion and immunofluorescence serological tests were carried out. Confrontation with the clinical and histopathologic diagnosis showed that the simultaneous use of mycological studies (of the bronchial aspirate) and of complex serologic investigations (immunodiffusion, immunofluorescence) allow to make a correcs and aspergilloses."}
{"id": "PMID:201017", "title": "[Angiography of the liver (author's transl)].", "content": "Angiography is a decisive technique of diagnosis of space-occupying processes in the liver. In contrast to laboratory-techniques, scintigraphy and ultrasound which ought to precede it, angiography permits a diagnosis of the type of lesion and is a guide to the chances of surgery on the basis of vascular topography. Angiographic findings in primary and secondary benign and malignant tumors of the liver, of cysts, abscesses and trauma are described and demonstrated on cases. The various forms of portal hypertension are a further field for angiographic diagnosis, explained on examples. The techniques of showing the hepatic arteries, the portal circulation and hepatic veins including direct portography are described and their usefulness for the various diseases discussed. The still little tested therapeutic use of liver angiography in hemorrhage and tumors is mentioned.", "contents": "[Angiography of the liver (author's transl)]. Angiography is a decisive technique of diagnosis of space-occupying processes in the liver. In contrast to laboratory-techniques, scintigraphy and ultrasound which ought to precede it, angiography permits a diagnosis of the type of lesion and is a guide to the chances of surgery on the basis of vascular topography. Angiographic findings in primary and secondary benign and malignant tumors of the liver, of cysts, abscesses and trauma are described and demonstrated on cases. The various forms of portal hypertension are a further field for angiographic diagnosis, explained on examples. The techniques of showing the hepatic arteries, the portal circulation and hepatic veins including direct portography are described and their usefulness for the various diseases discussed. The still little tested therapeutic use of liver angiography in hemorrhage and tumors is mentioned."}
{"id": "PMID:201012", "title": "[Idiopathic pulmonary hemosiderosis (2 clinical cases)].", "content": "The authors present two children with idiopathic pulmonary hemosiderosis, in whom the diagnosis was very difficult on the basis of evolution by stages, hypochromic anemia, hemoptoic sputum containing siderophages, cloudy pulmonary shadow and microscopical skin and lung examination that evidenced marked alterations of the elastic system and siderophages on pulmonary tissue preparations. All the clinical, hematologic and radiological signs were considerably improved by corticoid therapy. The necessity is stressed of such investigations in children with anemia.", "contents": "[Idiopathic pulmonary hemosiderosis (2 clinical cases)]. The authors present two children with idiopathic pulmonary hemosiderosis, in whom the diagnosis was very difficult on the basis of evolution by stages, hypochromic anemia, hemoptoic sputum containing siderophages, cloudy pulmonary shadow and microscopical skin and lung examination that evidenced marked alterations of the elastic system and siderophages on pulmonary tissue preparations. All the clinical, hematologic and radiological signs were considerably improved by corticoid therapy. The necessity is stressed of such investigations in children with anemia."}
{"id": "PMID:201021", "title": "Isozymes of creatine phosphokinase and myokinase in human heart and skeletal muscle.", "content": "The isozyme patterns of creatine phosphokinase (CPK) and myokinase (MK) were investigated in biopsy material from human heart and skeletal muscle. The protein separation was performed on crude muscle homogenates by means of flat-bed isoelectric focusing. Two isozymes were demonstrated for each enzyme, irrespective of the sampling site. The pI values were, on the average, 9.8 (MK-1) and 8.9 (MK-2), 7.2 (CPK-1) and 6.9 (CPK-2), respectively. MK-1 and CPK-1 constituted an average of 81% and 70% of total staining density for each enzyme, respectively. The relative contribution of MK-1 differed, however. Heart muscle showed the highest values (mean 91%) and vastus lateralis the lowest (mean 74%). The mean value for soleus was 86% MK-1. Furthermore, the percentage of MK-1 present was negatively correlated with the percentage of fast twitch fibres in m. vastus lateralis (r = -0.67). No corresponding differences could be demonstrated for CPK isozyme distribution. In conclusion, it was demonstrated that MK and CPK each occurred as two isozymes in human heart and skeletal muscle, and that the relative distribution of MK isozymes, in contrast to CPK, was related to muscle fibre type composition, and thus to the metabolic profile of the muscle.", "contents": "Isozymes of creatine phosphokinase and myokinase in human heart and skeletal muscle. The isozyme patterns of creatine phosphokinase (CPK) and myokinase (MK) were investigated in biopsy material from human heart and skeletal muscle. The protein separation was performed on crude muscle homogenates by means of flat-bed isoelectric focusing. Two isozymes were demonstrated for each enzyme, irrespective of the sampling site. The pI values were, on the average, 9.8 (MK-1) and 8.9 (MK-2), 7.2 (CPK-1) and 6.9 (CPK-2), respectively. MK-1 and CPK-1 constituted an average of 81% and 70% of total staining density for each enzyme, respectively. The relative contribution of MK-1 differed, however. Heart muscle showed the highest values (mean 91%) and vastus lateralis the lowest (mean 74%). The mean value for soleus was 86% MK-1. Furthermore, the percentage of MK-1 present was negatively correlated with the percentage of fast twitch fibres in m. vastus lateralis (r = -0.67). No corresponding differences could be demonstrated for CPK isozyme distribution. In conclusion, it was demonstrated that MK and CPK each occurred as two isozymes in human heart and skeletal muscle, and that the relative distribution of MK isozymes, in contrast to CPK, was related to muscle fibre type composition, and thus to the metabolic profile of the muscle."}
{"id": "PMID:201022", "title": "Increased plasma cyclic AMP concentrations in fasting man.", "content": "Plasma concentrations of adenosine 3', 5' monophosphate (cyclic AMP), free fatty acids (FFA), glycerol and glucose were measured after 24, 48 and 72 h fasting in healthy male students. There was a marked rise in plasma concentrations of cyclic AMP, FFA and glycerol from 24 to 48 h fasting with no further changes from 48 to 72 h fasting. Plasma glucose concentrations fell. After 72 h fasting, inhibition of adipose tissue lipolysis with a nicotinic acid analogue effected no significant change in plasma cyclic AMP concentrations, indicating that the elevated plasma nucleotide concentrations during fasting were not related to stimulation of lipolysis.", "contents": "Increased plasma cyclic AMP concentrations in fasting man. Plasma concentrations of adenosine 3', 5' monophosphate (cyclic AMP), free fatty acids (FFA), glycerol and glucose were measured after 24, 48 and 72 h fasting in healthy male students. There was a marked rise in plasma concentrations of cyclic AMP, FFA and glycerol from 24 to 48 h fasting with no further changes from 48 to 72 h fasting. Plasma glucose concentrations fell. After 72 h fasting, inhibition of adipose tissue lipolysis with a nicotinic acid analogue effected no significant change in plasma cyclic AMP concentrations, indicating that the elevated plasma nucleotide concentrations during fasting were not related to stimulation of lipolysis."}
{"id": "PMID:201025", "title": "Free radical increases in cancer: evidence that there is not a real increase.", "content": "The controversial finding of an increase in free radicals with the development of cancer was restudied with Walker 256 carcinosarcoma cells. It was confirmed that such an increase appears to occur, but it was also demonstrated that it is not a real increase. With growth of the tumor, the electron spin resonance lines for lyophilized samples became narrower, resulting in an increase in peak-to-peak height measurements, but there was no change in the total number of spins. The signals for lyophilized tumor samples were different from those for the same samples before lyophilization. Changes in line shape indicated that lyophilization. Changes in line shape indicated that lyophilized tumor samples contain a different mixture of radicals than lyophilized samples of normal tissue.", "contents": "Free radical increases in cancer: evidence that there is not a real increase. The controversial finding of an increase in free radicals with the development of cancer was restudied with Walker 256 carcinosarcoma cells. It was confirmed that such an increase appears to occur, but it was also demonstrated that it is not a real increase. With growth of the tumor, the electron spin resonance lines for lyophilized samples became narrower, resulting in an increase in peak-to-peak height measurements, but there was no change in the total number of spins. The signals for lyophilized tumor samples were different from those for the same samples before lyophilization. Changes in line shape indicated that lyophilization. Changes in line shape indicated that lyophilized tumor samples contain a different mixture of radicals than lyophilized samples of normal tissue."}
{"id": "PMID:201026", "title": "Regions of cerebral ischemia located by pyridine nucleotide fluorescence.", "content": "The fluorescence of the reduced form of the endogenous pyridine nucleotide nicotinamide adenine dinucleotide was used to map regions of ischemia in cat brain. A remarkably microheterogeneous pattern of increased fluorescence resulted from a critical level of incomplete cerebral ischemia. The fluorescence pattern suggests that ischemia occurs initially in microwatershed zones between penetrating cerebral arteries.", "contents": "Regions of cerebral ischemia located by pyridine nucleotide fluorescence. The fluorescence of the reduced form of the endogenous pyridine nucleotide nicotinamide adenine dinucleotide was used to map regions of ischemia in cat brain. A remarkably microheterogeneous pattern of increased fluorescence resulted from a critical level of incomplete cerebral ischemia. The fluorescence pattern suggests that ischemia occurs initially in microwatershed zones between penetrating cerebral arteries."}
{"id": "PMID:201027", "title": "Phosphoribosylpyrophosphate synthesis in cultured human cells.", "content": "Phosphoribosylpyrophosphate (PRPP) concentrations and PRPP synthetase activity were studied in cultured human fibroblasts with control and mutant hypoxanthine-guanine phosphoribosylpyrophosphate (HPRT) activity. The PRPP concentrations increased 20- to 50-fold and PRPP synthetase activity 3-fold in cells from patients with the Lesch-Nyham syndrome when aminopterin, an inhibitor of de novo purine synthesis, was added to the medium. Concentrations of PRPP and PRPP synthetase activity did not increase in control cells in medium containing aminopterin unless hypoxanthine was removed from the medium. Exposure of cells to cycloheximide, a protein synthesis inhibitor, prevented the induction of PRPP synthetase and the formation of high PRPP concentrations. Cells from a patient with a mutant HPRT with a high Michaelis constant for PRPP increased PRPP levels and PRPP synthetase activity to a new steady state when they were grown in medium containing aminopterin. Inhibitors of de novo purine synthesis, the presence of hypoxanthine in the medium, and mutant HPRT activity affect the regulation of PRPP levels and PRPP synthetase activity.", "contents": "Phosphoribosylpyrophosphate synthesis in cultured human cells. Phosphoribosylpyrophosphate (PRPP) concentrations and PRPP synthetase activity were studied in cultured human fibroblasts with control and mutant hypoxanthine-guanine phosphoribosylpyrophosphate (HPRT) activity. The PRPP concentrations increased 20- to 50-fold and PRPP synthetase activity 3-fold in cells from patients with the Lesch-Nyham syndrome when aminopterin, an inhibitor of de novo purine synthesis, was added to the medium. Concentrations of PRPP and PRPP synthetase activity did not increase in control cells in medium containing aminopterin unless hypoxanthine was removed from the medium. Exposure of cells to cycloheximide, a protein synthesis inhibitor, prevented the induction of PRPP synthetase and the formation of high PRPP concentrations. Cells from a patient with a mutant HPRT with a high Michaelis constant for PRPP increased PRPP levels and PRPP synthetase activity to a new steady state when they were grown in medium containing aminopterin. Inhibitors of de novo purine synthesis, the presence of hypoxanthine in the medium, and mutant HPRT activity affect the regulation of PRPP levels and PRPP synthetase activity."}
{"id": "PMID:201028", "title": "Structural basis for on-and off-center responses in retinal bipolar cells.", "content": "Electron microscopy of Golgi preparations of goldfish retina shows that dendrites of type a (hyperpolarizing, off-center) bipolar cells make wide cleft junctions unassociated with synaptic ribbons, while those of type b (depolarizing, on-center) bioplar cells make narrow cleft junctions and synaptic ribbon contacts, with rods and cones. This suggests that wide cleft junctions are the site of sign-conserving, and narrow cleft junctions or ribbon contacts (or both) are the site of sign-inverting synaptic transmission from photoreceptors to bipolars.", "contents": "Structural basis for on-and off-center responses in retinal bipolar cells. Electron microscopy of Golgi preparations of goldfish retina shows that dendrites of type a (hyperpolarizing, off-center) bipolar cells make wide cleft junctions unassociated with synaptic ribbons, while those of type b (depolarizing, on-center) bioplar cells make narrow cleft junctions and synaptic ribbon contacts, with rods and cones. This suggests that wide cleft junctions are the site of sign-conserving, and narrow cleft junctions or ribbon contacts (or both) are the site of sign-inverting synaptic transmission from photoreceptors to bipolars."}
{"id": "PMID:201029", "title": "[Muscular and nervous system manifestations of Graves' disease].", "content": "A study of 30 cases of Grave's disease confirmed the frequency of hyperthyroid myopathy, whether obvious or revealed by E.M.G. More than by the association of various symptoms (pretibial myxoedema, antithyroid antibodies), we were struck by the multiple symptoms of Grave's disease with myopathy, which confirms the anglo-saxon concept of the polysystemic nature of Grave's disease. This symptomatic richness is not necessarily proportional to the thyroid hypersecretion, and one may suppose that these patients have a greater peripheral sensitivity to the effects of hormone excess, which would explain the multiple clinical signs. The frequency of neuropathy seemed to us more important than usually believed. The clinical signs are often, or absent, or may be masked by the predominance of muscle wasting. If E.M.G. of the distal muscle and measurement of conduction rates were carried out more often as a routine, this would no doubt permit better assessment of the true frequency of neural involvement.", "contents": "[Muscular and nervous system manifestations of Graves' disease]. A study of 30 cases of Grave's disease confirmed the frequency of hyperthyroid myopathy, whether obvious or revealed by E.M.G. More than by the association of various symptoms (pretibial myxoedema, antithyroid antibodies), we were struck by the multiple symptoms of Grave's disease with myopathy, which confirms the anglo-saxon concept of the polysystemic nature of Grave's disease. This symptomatic richness is not necessarily proportional to the thyroid hypersecretion, and one may suppose that these patients have a greater peripheral sensitivity to the effects of hormone excess, which would explain the multiple clinical signs. The frequency of neuropathy seemed to us more important than usually believed. The clinical signs are often, or absent, or may be masked by the predominance of muscle wasting. If E.M.G. of the distal muscle and measurement of conduction rates were carried out more often as a routine, this would no doubt permit better assessment of the true frequency of neural involvement."}
{"id": "PMID:201030", "title": "[Action of bromocriptine on glucose metabolism in diabetics].", "content": "24 diabetics, (9 thin diabetics, 14 cases of maturity onset diabetes, 6 intermediate forms and one case of partial pancreatectomy) received 7.5 to 20 mg of bromocriptine (CB 154) per 24 hours. A definite improvement in glucose metabolism was noted in 6 cases, a definite aggravation in 4 cases; 14 results were not significant (p-0.05). The efficacy of CB 154 did not depend on the clinical type nor on the patient's age. It appeared related to duration of the diabetes (2 years and 3 months in improved patients, 11 years in aggravated patients) and perhaps the degree of retinopathy (more frequent and severe in aggravated patients). The improvement seems to be linked to the existence in certain diabetics of a paradoxical regulation of STH secretion as in acromegaly. The possibility of a peripheral effect of bromocriptine on insulin and glucagon is discussed. The CB 154 test (estimations of STH after a single dose of 2.5 mg) permits one to foresee the efficacy of the drug and perhaps the risk of diabetic retinopathy.", "contents": "[Action of bromocriptine on glucose metabolism in diabetics]. 24 diabetics, (9 thin diabetics, 14 cases of maturity onset diabetes, 6 intermediate forms and one case of partial pancreatectomy) received 7.5 to 20 mg of bromocriptine (CB 154) per 24 hours. A definite improvement in glucose metabolism was noted in 6 cases, a definite aggravation in 4 cases; 14 results were not significant (p-0.05). The efficacy of CB 154 did not depend on the clinical type nor on the patient's age. It appeared related to duration of the diabetes (2 years and 3 months in improved patients, 11 years in aggravated patients) and perhaps the degree of retinopathy (more frequent and severe in aggravated patients). The improvement seems to be linked to the existence in certain diabetics of a paradoxical regulation of STH secretion as in acromegaly. The possibility of a peripheral effect of bromocriptine on insulin and glucagon is discussed. The CB 154 test (estimations of STH after a single dose of 2.5 mg) permits one to foresee the efficacy of the drug and perhaps the risk of diabetic retinopathy."}
{"id": "PMID:201032", "title": "[Bilateral malignant exophthalmia as a manifestation of IgM multiple myeloma].", "content": "The authors report a case of IgM myeloma revealed by bilateral malignant exophtalmia, only the third case to be published in the world. This exophthalmia was due to plasma cell infiltration of the periorbital fat, and not to primary involvement of the orbit. Other rare localisations were found on autopsy: ovarian, pleuro-pulmonary and, above all, epicardiac. This was an IgM myeloma (0.5% of myelomatous disease) and not Waldenstrom's macroglobulinemia. In fact the patient had no adenopathy, no hepato or splenomegaly, and the tumour contained only plasma cells.", "contents": "[Bilateral malignant exophthalmia as a manifestation of IgM multiple myeloma]. The authors report a case of IgM myeloma revealed by bilateral malignant exophtalmia, only the third case to be published in the world. This exophthalmia was due to plasma cell infiltration of the periorbital fat, and not to primary involvement of the orbit. Other rare localisations were found on autopsy: ovarian, pleuro-pulmonary and, above all, epicardiac. This was an IgM myeloma (0.5% of myelomatous disease) and not Waldenstrom's macroglobulinemia. In fact the patient had no adenopathy, no hepato or splenomegaly, and the tumour contained only plasma cells."}
{"id": "PMID:201031", "title": "[Evanescent toxic thyroid adenoma. Possible role of phenylpropanolamine].", "content": "A patient with a toxic adenoma, already reduced in size by TSH, presented on the third day after treatment of a common cold by phenylpropanolomine, a severe pain in the thyroid gland. 4 weeks later, the nodule, which measured 3 x 4 cm. had clinically disappeared and the scan returned to normal. The disappearance 5 months later of the antithyroid antibodies confirmed the cure. Catecholamines, stimulating the production of thyroid hormone and producing temporary ischemia of the gland, phenylpropanolamine, a sympathomimetic drug, may have caused hemorrhagic necrosis of the adenoma and its disappearance.", "contents": "[Evanescent toxic thyroid adenoma. Possible role of phenylpropanolamine]. A patient with a toxic adenoma, already reduced in size by TSH, presented on the third day after treatment of a common cold by phenylpropanolomine, a severe pain in the thyroid gland. 4 weeks later, the nodule, which measured 3 x 4 cm. had clinically disappeared and the scan returned to normal. The disappearance 5 months later of the antithyroid antibodies confirmed the cure. Catecholamines, stimulating the production of thyroid hormone and producing temporary ischemia of the gland, phenylpropanolamine, a sympathomimetic drug, may have caused hemorrhagic necrosis of the adenoma and its disappearance."}
{"id": "PMID:201040", "title": "The in vitro and in vivo activity of taurolin against anaerobic pathogenic organisms.", "content": "An antibacterial agent, taurolin, formed by the combination of 2 molecules of taurine with 3 molecules of formaldehyde has been tested against anaerobes in vitro and in vivo. In vitro, taurolin is highly active against Bacteroides species and anaerobic Streptococci as measured by the minimum inhibitory concentration. In vivo, small dosages of taurolin given intraperitoneally increase the mortality in mice with Bacteroides peritonitis. However, by increasing the dosage of taurolin, survival is prolonged and mortality reduced. Intravenously administered taurolin protects rabbits from the effects of Bacteroides fragilis infection whether the organisms are given intravenously or intraperitoneally.", "contents": "The in vitro and in vivo activity of taurolin against anaerobic pathogenic organisms. An antibacterial agent, taurolin, formed by the combination of 2 molecules of taurine with 3 molecules of formaldehyde has been tested against anaerobes in vitro and in vivo. In vitro, taurolin is highly active against Bacteroides species and anaerobic Streptococci as measured by the minimum inhibitory concentration. In vivo, small dosages of taurolin given intraperitoneally increase the mortality in mice with Bacteroides peritonitis. However, by increasing the dosage of taurolin, survival is prolonged and mortality reduced. Intravenously administered taurolin protects rabbits from the effects of Bacteroides fragilis infection whether the organisms are given intravenously or intraperitoneally."}
{"id": "PMID:201041", "title": "Depletion of replenishment of cellular cyclic adenosine monophosphate in hemorrhagic shock.", "content": "Hemorrhagic shock in rats was produced by bleeding them to a mean arterial blood pressure of 40 millimeters of mercury, which was maintained for two hours. After sacrifice, small pieces of liver, kidney, muscle and brain were quickly removed and frozen in liquid nitrogen. A protein-free extract of tissues was prepared, and cyclic adenosine monophosphate was measured by the radioimmunoassay procedure. Analysis os liver, kidney, muscle and brain showed that there were significant reductions in cyclic adenosine monophosphate and adenosine triphosphate levels. The decrease in cyclic adenosine monophosphate levels follow the same trend in the various organs as the decreases in adenosine triphosphate levels, suggesting that these two events are related. Infusion of adenosine triphosphate-magnesium chloride, 25 micromoles each, at the end of the shock period restored the cellular cyclic adenosine monophosphate and adenosine triphosphate levels. The precise mechanism for depletion and replenishment of cyclic adenosine monophosphate levels during shock is not now known.", "contents": "Depletion of replenishment of cellular cyclic adenosine monophosphate in hemorrhagic shock. Hemorrhagic shock in rats was produced by bleeding them to a mean arterial blood pressure of 40 millimeters of mercury, which was maintained for two hours. After sacrifice, small pieces of liver, kidney, muscle and brain were quickly removed and frozen in liquid nitrogen. A protein-free extract of tissues was prepared, and cyclic adenosine monophosphate was measured by the radioimmunoassay procedure. Analysis os liver, kidney, muscle and brain showed that there were significant reductions in cyclic adenosine monophosphate and adenosine triphosphate levels. The decrease in cyclic adenosine monophosphate levels follow the same trend in the various organs as the decreases in adenosine triphosphate levels, suggesting that these two events are related. Infusion of adenosine triphosphate-magnesium chloride, 25 micromoles each, at the end of the shock period restored the cellular cyclic adenosine monophosphate and adenosine triphosphate levels. The precise mechanism for depletion and replenishment of cyclic adenosine monophosphate levels during shock is not now known."}
{"id": "PMID:201044", "title": "Patterns of combined limb malformations.", "content": "Seven different limb malformations types were defined in 544 affected newborns, apparently free from other anomalies, obtained from a series of 297,299 livebirths. These seven malformation types were: polydactyly, limb reduction, brachydactyly, symphalangy, syndactyly and split hand/foot. One anomaly type was present in 472 newborns (1.58/1,000) and two or three in 72 (0.24/1,000). The observed combinations of two or three limb malformation types cannot be explained as chance association. Therefore, a common etiopathogenic mechanism has to be considered when two or more limb malformation types are combined in a given individual. The most frequent observed combinations were: reduction-brachydactyly, reduction-syndactyly, brachydactyly-syndactyly, polydactyly-syndactyly, and reduction-brachydactyly-syndactyly. Based on affected limb distribution, sex ratio, and familial recurrence rates, it is suggest that a reduction anomaly is the primary component in all tested combinations while syndactyly tends to be a secondary one when combined with any other limb anomaly type.", "contents": "Patterns of combined limb malformations. Seven different limb malformations types were defined in 544 affected newborns, apparently free from other anomalies, obtained from a series of 297,299 livebirths. These seven malformation types were: polydactyly, limb reduction, brachydactyly, symphalangy, syndactyly and split hand/foot. One anomaly type was present in 472 newborns (1.58/1,000) and two or three in 72 (0.24/1,000). The observed combinations of two or three limb malformation types cannot be explained as chance association. Therefore, a common etiopathogenic mechanism has to be considered when two or more limb malformation types are combined in a given individual. The most frequent observed combinations were: reduction-brachydactyly, reduction-syndactyly, brachydactyly-syndactyly, polydactyly-syndactyly, and reduction-brachydactyly-syndactyly. Based on affected limb distribution, sex ratio, and familial recurrence rates, it is suggest that a reduction anomaly is the primary component in all tested combinations while syndactyly tends to be a secondary one when combined with any other limb anomaly type."}
{"id": "PMID:201046", "title": "Studies of isolated adult rat heart cells: the surface morphology and the influence of extracellular calcium ion concentration on cellular viability.", "content": "Rat cardiac muscle was dissociated into single cells by a coronary perfusion technique with collagenase and hyaluronidase in a Ca-free medium. Retention of the cylindrical shape of isolated muscle cells could be achieved by regulation of [Ca2+]0 and temperature. Cells kept at 4 degrees C, and 0-01 mM CaCl2 remained cylindrical for more than a week and contracted spontaneously upon warming at 37 degrees C. At [Ca2+]0 between 0-1-2 mM and 37 degrees C, cells underwent contracture and rounded up. Scanning (SEM) and transmission electron microscopy were used to analyze the structure of cylindrical and rounded muscle cells. The extracellular aspect of the sarcolemma at lateral cell surfaces and intercalated disc regions were clearly revealed for SEM analysis. Both the distribution and number of T-tubule openings on the surfaces can be estimated and a three-dimensional description of the intercalated disc obtained. This study reveals that isolated adult heart cells are extremely sensitive to [Ca2+]0, but with careful control of this cation, this preparation should be helpful in the analysis of both sarcolemmal structure and the pathological changes which accompany myocardial injury.", "contents": "Studies of isolated adult rat heart cells: the surface morphology and the influence of extracellular calcium ion concentration on cellular viability. Rat cardiac muscle was dissociated into single cells by a coronary perfusion technique with collagenase and hyaluronidase in a Ca-free medium. Retention of the cylindrical shape of isolated muscle cells could be achieved by regulation of [Ca2+]0 and temperature. Cells kept at 4 degrees C, and 0-01 mM CaCl2 remained cylindrical for more than a week and contracted spontaneously upon warming at 37 degrees C. At [Ca2+]0 between 0-1-2 mM and 37 degrees C, cells underwent contracture and rounded up. Scanning (SEM) and transmission electron microscopy were used to analyze the structure of cylindrical and rounded muscle cells. The extracellular aspect of the sarcolemma at lateral cell surfaces and intercalated disc regions were clearly revealed for SEM analysis. Both the distribution and number of T-tubule openings on the surfaces can be estimated and a three-dimensional description of the intercalated disc obtained. This study reveals that isolated adult heart cells are extremely sensitive to [Ca2+]0, but with careful control of this cation, this preparation should be helpful in the analysis of both sarcolemmal structure and the pathological changes which accompany myocardial injury."}
{"id": "PMID:201047", "title": "Effects of dibutyryl cyclic-AMP on cardiac output and myocardial contractility in dogs.", "content": "Dibutyryl cyclic-AMP was administered to a group of anesthetized dogs at the doses of 5, 10, 20 and 40 mg/kg, and changes in stroke volume, cardiac output and myocardial contractility were observed. Also, effects of this substance on contractile performance of isolated cardiac muscle were investigated in another group of dogs. Results were as follows: 1) Dibutyryl cyclic-AMP increased heart rate, stroke volume and cardiac output in a dose-related manner in the range from 5 to 40 mg/kg. 2) As indices of myocardial contractility, Vmax and maximum dF/dt were examined. These also showed a dose-dependent increase in response to dibutyryl cyclic-AMP. In isolated dog hearts, dibutyryl cyclic-AMP raised the maximum velocity of shortening (V'max) dose-dependently. 3) Total peripheral resistance declined in a dose-related way. On the other hand, mean arterial pressure and CVP dropped slightly without showing dose-dependence. These results show that dibutyryl cyclic-AMP produces positive inotropic and chronotropic effects and cause dilatation of the peripheral vessels in dose-dependent manners.", "contents": "Effects of dibutyryl cyclic-AMP on cardiac output and myocardial contractility in dogs. Dibutyryl cyclic-AMP was administered to a group of anesthetized dogs at the doses of 5, 10, 20 and 40 mg/kg, and changes in stroke volume, cardiac output and myocardial contractility were observed. Also, effects of this substance on contractile performance of isolated cardiac muscle were investigated in another group of dogs. Results were as follows: 1) Dibutyryl cyclic-AMP increased heart rate, stroke volume and cardiac output in a dose-related manner in the range from 5 to 40 mg/kg. 2) As indices of myocardial contractility, Vmax and maximum dF/dt were examined. These also showed a dose-dependent increase in response to dibutyryl cyclic-AMP. In isolated dog hearts, dibutyryl cyclic-AMP raised the maximum velocity of shortening (V'max) dose-dependently. 3) Total peripheral resistance declined in a dose-related way. On the other hand, mean arterial pressure and CVP dropped slightly without showing dose-dependence. These results show that dibutyryl cyclic-AMP produces positive inotropic and chronotropic effects and cause dilatation of the peripheral vessels in dose-dependent manners."}
{"id": "PMID:201050", "title": "[Effects of methylcyclopentadienyl manganese tricarbonyl (MMT) on rat liver mitochondria. II. Activity-structure relation (author's transl)].", "content": "The action of various manganese organic compounds, which are structural analogs of methylcyclopentadienyl manganese tricarbonyl (MMT), was investigated. Only the cyclopentadienyl manganese tricarbonyl compounds are effective inhibitors of mitochondrial respiration, but only when associated with NAD+-linked substrates. The manganese tricarbonyl group is required for this mitochondrial respiration inhibition. The substitutions operated on the cyclopentadienyl cycle also interfere and increase the inhibitory effect. Meanwhile, the benzoyl and thenoyl groups are more effective than the methyl group. The effects of the various compounds result from their special electronic configuration.", "contents": "[Effects of methylcyclopentadienyl manganese tricarbonyl (MMT) on rat liver mitochondria. II. Activity-structure relation (author's transl)]. The action of various manganese organic compounds, which are structural analogs of methylcyclopentadienyl manganese tricarbonyl (MMT), was investigated. Only the cyclopentadienyl manganese tricarbonyl compounds are effective inhibitors of mitochondrial respiration, but only when associated with NAD+-linked substrates. The manganese tricarbonyl group is required for this mitochondrial respiration inhibition. The substitutions operated on the cyclopentadienyl cycle also interfere and increase the inhibitory effect. Meanwhile, the benzoyl and thenoyl groups are more effective than the methyl group. The effects of the various compounds result from their special electronic configuration."}
{"id": "PMID:201052", "title": "Effects of cobalt-60 gamma-irradiation in association with prostaglandin E1 treatment on the cyclic AMP levels of some radiosensitive tissues.", "content": "The amounts of cyclic AMP in brain, liver and intestinal mucosa have been measured in rats, at constant intervals, up to 18 days after whole-body exposure to either a unique moderate dose (500 rd) or a unique lethal dose (750 rd) of cobalt-60 gamma-radiation in association with a preliminary intraperitoneally treatment with prostaglandin E1 (5 microgram/100 g body weight/day) during five days. The amounts of tissular cyclic AMP in these two experimental groups were compared with those obtained from control groups identically irradiated or treated with prostaglandin E1. The effects of gamma-irradiation and prostaglandin E1 treatment on the cyclic AMP levels were found to be quite specific in these organs, suggesting that they contain different adenyl cyclase-cyclic AMP-phosphodiesterase systems: a cerebral system which is influenced by both gamma-radiation and prostaglandin E1, a hepatic system which is \"radioresistant\" and an intestinal system which is not influenced by prostaglandin E1. When associated with gamma-radiation, this prostaglandin is capable, on the one hand, to annul the \"radioresistance\" of the hepatic cyclic AMP system and, on the other hand, to annul the \"radiosensitivity\" of the intestinal cyclic AMP system.", "contents": "Effects of cobalt-60 gamma-irradiation in association with prostaglandin E1 treatment on the cyclic AMP levels of some radiosensitive tissues. The amounts of cyclic AMP in brain, liver and intestinal mucosa have been measured in rats, at constant intervals, up to 18 days after whole-body exposure to either a unique moderate dose (500 rd) or a unique lethal dose (750 rd) of cobalt-60 gamma-radiation in association with a preliminary intraperitoneally treatment with prostaglandin E1 (5 microgram/100 g body weight/day) during five days. The amounts of tissular cyclic AMP in these two experimental groups were compared with those obtained from control groups identically irradiated or treated with prostaglandin E1. The effects of gamma-irradiation and prostaglandin E1 treatment on the cyclic AMP levels were found to be quite specific in these organs, suggesting that they contain different adenyl cyclase-cyclic AMP-phosphodiesterase systems: a cerebral system which is influenced by both gamma-radiation and prostaglandin E1, a hepatic system which is \"radioresistant\" and an intestinal system which is not influenced by prostaglandin E1. When associated with gamma-radiation, this prostaglandin is capable, on the one hand, to annul the \"radioresistance\" of the hepatic cyclic AMP system and, on the other hand, to annul the \"radiosensitivity\" of the intestinal cyclic AMP system."}
{"id": "PMID:201053", "title": "Progesterone interaction with estrogen and antiestrogen in the rat uterus--receptor effects.", "content": "Daily injections of estradiol or the antiestrogen tamoxifen initially stimulate uterine weight increase and progesterone receptor synthesis, though continued tamoxifen fails to maintain the increased weight. The stimulatory actions of both estradiol and tamoxifen are inhibited or reversed by a single injection of progesterone. It has been hypothesized that progesterone antagonizes estrogen action by reducing estrogen receptor levels, but in the present experiments neither cytoplasmic nor nuclear estrogen receptor was affected. We conclude that progesterone acts at a point beyond estrogen receptor availability or translocation to antagonize estrogen action.", "contents": "Progesterone interaction with estrogen and antiestrogen in the rat uterus--receptor effects. Daily injections of estradiol or the antiestrogen tamoxifen initially stimulate uterine weight increase and progesterone receptor synthesis, though continued tamoxifen fails to maintain the increased weight. The stimulatory actions of both estradiol and tamoxifen are inhibited or reversed by a single injection of progesterone. It has been hypothesized that progesterone antagonizes estrogen action by reducing estrogen receptor levels, but in the present experiments neither cytoplasmic nor nuclear estrogen receptor was affected. We conclude that progesterone acts at a point beyond estrogen receptor availability or translocation to antagonize estrogen action."}
{"id": "PMID:201055", "title": "Effect of estrogens on the acitivities of cholesteryl ester synthetase and cholesteryl ester hydrolases in pigeon aorta.", "content": "This study is the first to report the effect of conjugated equine estrogens on the acitivity of cholesteryl ester synthetase and cholesteryl ester hydrolases in the aorta. In spontaneously atherosclerosis-susceptible White Carneau pigeons, estrogens significantly decreased (P less 0.01) the activity of cholesteryl ester synthetase and increased (P less than 0.01) the cholesteryl ester hydrolase activity in the microsomal fraction of the aorta. There was no effect on the cholesteryl ester hydrolase activity in the supernatant fraction. The inhibition of cholesteryl ester synthesis and the stimulation of cholesteryl ester hydrolase might be responsible for the decreased content of cholesteryl esters noted in pigeon aorta after estrogen treatment.", "contents": "Effect of estrogens on the acitivities of cholesteryl ester synthetase and cholesteryl ester hydrolases in pigeon aorta. This study is the first to report the effect of conjugated equine estrogens on the acitivity of cholesteryl ester synthetase and cholesteryl ester hydrolases in the aorta. In spontaneously atherosclerosis-susceptible White Carneau pigeons, estrogens significantly decreased (P less 0.01) the activity of cholesteryl ester synthetase and increased (P less than 0.01) the cholesteryl ester hydrolase activity in the microsomal fraction of the aorta. There was no effect on the cholesteryl ester hydrolase activity in the supernatant fraction. The inhibition of cholesteryl ester synthesis and the stimulation of cholesteryl ester hydrolase might be responsible for the decreased content of cholesteryl esters noted in pigeon aorta after estrogen treatment."}
{"id": "PMID:201056", "title": "[Antigenic rearrangement in the liver of mice and rats as a result of simultaneous effect of the carcinogens].", "content": "The antigenic structure of the livers of mice and rats after a single hepatocarcinogenic treatment was investigated using the immunodiffuse and immunofluorescent methods. The next day after carcinogen application changes characteristic of hepatocellular tumors were observed: decrease in the synthesis of organospecific antigens and intensification of the synthesis of heteroorganic antigens.", "contents": "[Antigenic rearrangement in the liver of mice and rats as a result of simultaneous effect of the carcinogens]. The antigenic structure of the livers of mice and rats after a single hepatocarcinogenic treatment was investigated using the immunodiffuse and immunofluorescent methods. The next day after carcinogen application changes characteristic of hepatocellular tumors were observed: decrease in the synthesis of organospecific antigens and intensification of the synthesis of heteroorganic antigens."}
{"id": "PMID:201057", "title": "[Effect of thyroxine, insulin and cholesterol on the amount of cyclic adenosine monophosphate in normal and oncornavirus infected cells].", "content": "The intracellular concentration of cyclic AMP in normal cells and in cells infected with the Rous sarcoma virus (chicken fibroblasts) was determined by the method of saturation analysis (method of concurrent binding with protein). Thyroxine (2 mcg/ml) increased the level of cyclic AMP both in normal and infected cells, insulin (2 mcg/ml) decreased the concentration of cyclic AMP in infected cells, but cholesterol (5 mcg/ml) exerted no effect on this parameter in infected cells. The data are discussed from the point of view of a possible influence of hormones on the cholesterol accumulation in cells and on the adenylatecyclase activity in cell membranes.", "contents": "[Effect of thyroxine, insulin and cholesterol on the amount of cyclic adenosine monophosphate in normal and oncornavirus infected cells]. The intracellular concentration of cyclic AMP in normal cells and in cells infected with the Rous sarcoma virus (chicken fibroblasts) was determined by the method of saturation analysis (method of concurrent binding with protein). Thyroxine (2 mcg/ml) increased the level of cyclic AMP both in normal and infected cells, insulin (2 mcg/ml) decreased the concentration of cyclic AMP in infected cells, but cholesterol (5 mcg/ml) exerted no effect on this parameter in infected cells. The data are discussed from the point of view of a possible influence of hormones on the cholesterol accumulation in cells and on the adenylatecyclase activity in cell membranes."}
{"id": "PMID:201058", "title": "[Migration of transformed fibroblast-like cells on substrates with patterned relief-work (quantitative study)].", "content": "The quantitative estimation of migration ability of transformed fibroblast-like cells of various epecies (mouse , rat, hamster, man) cultured on the substratum with grooves of various depth (5--40 mcm) was performed. Of the majority of 11 cell lines examined, a reduced migration capacity up to its total disappeanance was registered as compared with the homological normal embryonic cells. A  more pronounced reduction of migration ability was shown in mouse and rat transformed cells and less in human ones. Migration of transformed hamster cells was just equal to the weak migrtion of normal hamster embryonis cells. These data shown a weak response of the analysed transformed cells to the relief of underlying substratum.", "contents": "[Migration of transformed fibroblast-like cells on substrates with patterned relief-work (quantitative study)]. The quantitative estimation of migration ability of transformed fibroblast-like cells of various epecies (mouse , rat, hamster, man) cultured on the substratum with grooves of various depth (5--40 mcm) was performed. Of the majority of 11 cell lines examined, a reduced migration capacity up to its total disappeanance was registered as compared with the homological normal embryonic cells. A  more pronounced reduction of migration ability was shown in mouse and rat transformed cells and less in human ones. Migration of transformed hamster cells was just equal to the weak migrtion of normal hamster embryonis cells. These data shown a weak response of the analysed transformed cells to the relief of underlying substratum."}
{"id": "PMID:201060", "title": "[Spatial-temporal organization of mitochondria in nerve cells during rest and excitation].", "content": "Spatial reorganization of mitochondria in the nerve cell reflects, at the microstructural level, the control of its respiration and oxidative metabolism. During the first two minutes of excitation no changes are observed in the degree of mitochondrion aggregation, while cytochrome oxidase activity in them sharply increases. When the frequency of pulse activity stabilizes, mitochondria aggregate, cytochrome oxidase activity decreases, mainly in the aggregated mitochondria.", "contents": "[Spatial-temporal organization of mitochondria in nerve cells during rest and excitation]. Spatial reorganization of mitochondria in the nerve cell reflects, at the microstructural level, the control of its respiration and oxidative metabolism. During the first two minutes of excitation no changes are observed in the degree of mitochondrion aggregation, while cytochrome oxidase activity in them sharply increases. When the frequency of pulse activity stabilizes, mitochondria aggregate, cytochrome oxidase activity decreases, mainly in the aggregated mitochondria."}
{"id": "PMID:201061", "title": "Antigenic proteins of nucleolar chromatin of Novikoff hepatoma ascites cells.", "content": "Nucleolar chromatin of Novikoff hepatoma ascites cells contains an antigen (no-Ag1) detected with antinucleolar antibodies by the immunodiffusion technique. This antigen was distinguished from the previously reported nuclear chromatin antigen NAg-1 (19) by the findings that tumor nucleolar antibodies which formed immunoprecipitin bands with no-Ag1 did not do so with NAg-1 and that tumor cytosol, which contains NAg-1, formed immunoprecipitin bands with tumor chromatin antibodies but not with antibodies to tumor nucleoli. Tumor nucleolar chromatin contains both NAg-1 and no-Ag1, but only no-Ag1 formed bands with tumor nucleolar antibodies, no-Ag1 is a component of tumor nucleolar chromatin that was not soluble in 0.075 M NaCl-0.025 M EDTA, pH 8, and only slightly soluble in 0.01 M Tris-HCl, pH 8. NO-Ag1 was not found in liver nucleoli. Antibodies to liver nucleoli formed immunoprecipitin bands with liver nucleolar antigens but none were confluent with those formed between tumor nucleolar antibodies and antigens of tumor nucleolar chromatin. Absorption of the tumor nucleolar antibodies with whole tumor cells or whole liver pressate did not alter band formation with no-Ag1. Three antigens in liver nucleoli were not found in tumor nucleoli.", "contents": "Antigenic proteins of nucleolar chromatin of Novikoff hepatoma ascites cells. Nucleolar chromatin of Novikoff hepatoma ascites cells contains an antigen (no-Ag1) detected with antinucleolar antibodies by the immunodiffusion technique. This antigen was distinguished from the previously reported nuclear chromatin antigen NAg-1 (19) by the findings that tumor nucleolar antibodies which formed immunoprecipitin bands with no-Ag1 did not do so with NAg-1 and that tumor cytosol, which contains NAg-1, formed immunoprecipitin bands with tumor chromatin antibodies but not with antibodies to tumor nucleoli. Tumor nucleolar chromatin contains both NAg-1 and no-Ag1, but only no-Ag1 formed bands with tumor nucleolar antibodies, no-Ag1 is a component of tumor nucleolar chromatin that was not soluble in 0.075 M NaCl-0.025 M EDTA, pH 8, and only slightly soluble in 0.01 M Tris-HCl, pH 8. NO-Ag1 was not found in liver nucleoli. Antibodies to liver nucleoli formed immunoprecipitin bands with liver nucleolar antigens but none were confluent with those formed between tumor nucleolar antibodies and antigens of tumor nucleolar chromatin. Absorption of the tumor nucleolar antibodies with whole tumor cells or whole liver pressate did not alter band formation with no-Ag1. Three antigens in liver nucleoli were not found in tumor nucleoli."}
{"id": "PMID:201062", "title": "A melanotic neuroectodermal tumor of infancy arising from the anterior fontanel.", "content": "A case of local recurrence of melanotic neuroectodermal tumor of infancy (MNT), arising from the anterior fontanel in a 6-month-old female, is presented. The follow-up of 48 months after surgery confirms the benign nature of this tumor despite its local recurrence. Clinical and histopathologic chracteristics of this rare tumor are discussed. A review of 12 cases of MNT involving the skull is given. It is emphasized that this entity should be kept in mind in the differential diagnosis of a mass in the craniofacial structures in infancy.", "contents": "A melanotic neuroectodermal tumor of infancy arising from the anterior fontanel. A case of local recurrence of melanotic neuroectodermal tumor of infancy (MNT), arising from the anterior fontanel in a 6-month-old female, is presented. The follow-up of 48 months after surgery confirms the benign nature of this tumor despite its local recurrence. Clinical and histopathologic chracteristics of this rare tumor are discussed. A review of 12 cases of MNT involving the skull is given. It is emphasized that this entity should be kept in mind in the differential diagnosis of a mass in the craniofacial structures in infancy."}
{"id": "PMID:201064", "title": "The ultrastructure of malignant fibrous histiocytoma (case report).", "content": "A soft tissue malignant fibrous histiocytoma was studied by light and electron microscopy. The presence of fibroblast-like cells, histiocyte-like cells, undifferentiated stem cells, and xanthomatous cells was confirmed. Fibroblast- and histiocyte-like multinucleated giant cells were also observed. The observation of lysosomes in some fibroblast-like cells, the features of undifferentiated stem cells, and the presence of cells and intermediate characteristics common to xanthomatous, histiocytic, and stem cells suggest a strict relationship among these cellular types.", "contents": "The ultrastructure of malignant fibrous histiocytoma (case report). A soft tissue malignant fibrous histiocytoma was studied by light and electron microscopy. The presence of fibroblast-like cells, histiocyte-like cells, undifferentiated stem cells, and xanthomatous cells was confirmed. Fibroblast- and histiocyte-like multinucleated giant cells were also observed. The observation of lysosomes in some fibroblast-like cells, the features of undifferentiated stem cells, and the presence of cells and intermediate characteristics common to xanthomatous, histiocytic, and stem cells suggest a strict relationship among these cellular types."}
{"id": "PMID:201065", "title": "[Content of free amino acids in rabbit tissues as affected by adrenalectomy and administration of hydrocortisone and ACTH].", "content": "Adrenalectomy is accompanied by a decreased content of free amino acids in muscules and blood plasma by an increased content of certain amino acids in the liver. A single injection of hydrocortisone to adrenalectomized animals increases the content of amino acids in muscles and lowers their total content in the liver; a single injection of ACTH lowers the total content of amino acids in the liver and blood plasma \"Substitutive therapy\" by hydrocortisone essentially increases the content of amino acids in the liver, muscles and blood plasma. Under conditions of the experiment the least changes in the content of amino acids were found in the brain tissue.", "contents": "[Content of free amino acids in rabbit tissues as affected by adrenalectomy and administration of hydrocortisone and ACTH]. Adrenalectomy is accompanied by a decreased content of free amino acids in muscules and blood plasma by an increased content of certain amino acids in the liver. A single injection of hydrocortisone to adrenalectomized animals increases the content of amino acids in muscles and lowers their total content in the liver; a single injection of ACTH lowers the total content of amino acids in the liver and blood plasma \"Substitutive therapy\" by hydrocortisone essentially increases the content of amino acids in the liver, muscles and blood plasma. Under conditions of the experiment the least changes in the content of amino acids were found in the brain tissue."}
{"id": "PMID:201063", "title": "An Italian case of nasopharyngeal carcinoma correlated with Epstein-Barr virus specific antigens.", "content": "An Italian case of nasopharyngeal carcinoma was studied clinically; the immunologic study showed the correlation with the Epstein-Barr virus specific antigen.", "contents": "An Italian case of nasopharyngeal carcinoma correlated with Epstein-Barr virus specific antigens. An Italian case of nasopharyngeal carcinoma was studied clinically; the immunologic study showed the correlation with the Epstein-Barr virus specific antigen."}
{"id": "PMID:201067", "title": "[Effect of carbostimulin and vitamin D3 on activity of glycolytic enzymes of rabbit bones, regenerates and muscles].", "content": "Activity of glycolysis enzymes such as: phosphofructokinase, aldolase, phosphoglucomutase, was determined in the regenerate of a bone, bone fragments, native bone and, for the sake of comparison, in the animal muscles after the radius resection and feeding of carbostimulin and its mixture with vitamin D3 for 10 days. On the 12th day after the radius resection the phosphofructokinase activity in rabbits increases in the native and operated bones as compared to that in bones of nonoperative animals. In the group of rabbits which were fed on the mixture of carbostimulin and vitamin D3 the phosphofructokinase activity is 7-2 times as high. In the regenerate of these animals the activity becomes 12 times as high as that in the regenerate of the control rabbits. An analogous increase in the aldolase and phosphoglucomutase reaction rate is observed in the bones of the animals which received carbostimulin and vitamin D3 (4.5 and 7.5 times, respectively). The same tendency to the increase in the activity of these enzymes is observed in the regenerate tissue. In the muscular tissue at this stage of regeneration the activity of the studied enzymes which is usually high in norm decreases.", "contents": "[Effect of carbostimulin and vitamin D3 on activity of glycolytic enzymes of rabbit bones, regenerates and muscles]. Activity of glycolysis enzymes such as: phosphofructokinase, aldolase, phosphoglucomutase, was determined in the regenerate of a bone, bone fragments, native bone and, for the sake of comparison, in the animal muscles after the radius resection and feeding of carbostimulin and its mixture with vitamin D3 for 10 days. On the 12th day after the radius resection the phosphofructokinase activity in rabbits increases in the native and operated bones as compared to that in bones of nonoperative animals. In the group of rabbits which were fed on the mixture of carbostimulin and vitamin D3 the phosphofructokinase activity is 7-2 times as high. In the regenerate of these animals the activity becomes 12 times as high as that in the regenerate of the control rabbits. An analogous increase in the aldolase and phosphoglucomutase reaction rate is observed in the bones of the animals which received carbostimulin and vitamin D3 (4.5 and 7.5 times, respectively). The same tendency to the increase in the activity of these enzymes is observed in the regenerate tissue. In the muscular tissue at this stage of regeneration the activity of the studied enzymes which is usually high in norm decreases."}
{"id": "PMID:201069", "title": "[Adenylate cyclase system and its interrelation with muscle function].", "content": "The article deals with the data of the recent years on localization, structural organization and function of the adenylate cyclase system enzymes. They are mainly membrane-linked enzymes responsible for perception, transformation and transmission of signals of nervous and humoral systems from the cell surface to its internal part, right up the genetic apparatus. The enzymes are characterized catalyzing formation and transformation of cAMP-adenylate cyclase, phosphodisterase and enzymes by means of which intracellular metabolism is regulated with participation of cAMP-protein kinases and phosphoproteinphosphatases. The data are systematized as to possible interrelation of the adenylate cyclatase system function with calcium ion exchange. Attention is concentrated on the system possible role in the transport of this important cation, particularly in ensuring the function of the organism contractile systems.", "contents": "[Adenylate cyclase system and its interrelation with muscle function]. The article deals with the data of the recent years on localization, structural organization and function of the adenylate cyclase system enzymes. They are mainly membrane-linked enzymes responsible for perception, transformation and transmission of signals of nervous and humoral systems from the cell surface to its internal part, right up the genetic apparatus. The enzymes are characterized catalyzing formation and transformation of cAMP-adenylate cyclase, phosphodisterase and enzymes by means of which intracellular metabolism is regulated with participation of cAMP-protein kinases and phosphoproteinphosphatases. The data are systematized as to possible interrelation of the adenylate cyclatase system function with calcium ion exchange. Attention is concentrated on the system possible role in the transport of this important cation, particularly in ensuring the function of the organism contractile systems."}
{"id": "PMID:201068", "title": "[Study of cytoplasmic RNA in tissues of the rat, regenerating liver and in liver of rats with hepatoma PC-1].", "content": "Cytoplasmic RNA of the rat regenerating liver and liver of rats with hepatoma PC-1 is separated into five fractions on the column of kieselgur with methylated albumin (MAK). Studies in the nucleotide composition showed that certain fractions of cytoplasm RNA are ribosomal and messenger RNA. The highest amount of radioactive precursor is incorporated into messenger RNA of the rat regenerating liver and liver of the rats with hepatoma PC-1 which is eluated from the column by 0.2% solution of sodium dodecyl sulphate at 37 degrees C (third fraction). Actinomycin D in doses inhibiting appearance of characteristic proteins in the blood serum of rats with the regenerating liver and heaptoma PC-1 blocks almost completely biosynthesis of ribosomal RNA eluated from the MAK column in the gradient of sodium chloride (second fraction), and that of messenger RNA, eluated by sodium dodecyl-sulphate at 37 degrees C (third fraction).", "contents": "[Study of cytoplasmic RNA in tissues of the rat, regenerating liver and in liver of rats with hepatoma PC-1]. Cytoplasmic RNA of the rat regenerating liver and liver of rats with hepatoma PC-1 is separated into five fractions on the column of kieselgur with methylated albumin (MAK). Studies in the nucleotide composition showed that certain fractions of cytoplasm RNA are ribosomal and messenger RNA. The highest amount of radioactive precursor is incorporated into messenger RNA of the rat regenerating liver and liver of the rats with hepatoma PC-1 which is eluated from the column by 0.2% solution of sodium dodecyl sulphate at 37 degrees C (third fraction). Actinomycin D in doses inhibiting appearance of characteristic proteins in the blood serum of rats with the regenerating liver and heaptoma PC-1 blocks almost completely biosynthesis of ribosomal RNA eluated from the MAK column in the gradient of sodium chloride (second fraction), and that of messenger RNA, eluated by sodium dodecyl-sulphate at 37 degrees C (third fraction)."}
{"id": "PMID:201075", "title": "Pathology of adenoviral infection in turkeys (Meleagris gallopavo) with respiratory disease and colisepticemia.", "content": "Nuclear inclusion bodies typical of the adenovirus group were widespread in in the spleen and other tissues of 8-week-old turkeys with severe respiratory disease and concomitant evidence of colisepticemia. Adenoviral virions were seen in affected nuclei of splenic tissue and in negatively stained preparations of ground spleen. In splenic tissue, inclusions were most prominent in reticular cells and macrophages in the periarterial lymphoid sheaths, the red pulp and the marginal zones of the periarteriolar reticular sheaths. Marked reticuloendothelial hyperplasia, lymphoid atrophy and granulocytic splenitis characterized the splenic changes. There were inclusions in the respiratory tract, intestinal tract, liver, kidney and pancreas. Inoculation of young turkeys, especially when immunosuppressed, resulted in evidence of infection and respiratory disease. The viruses produced cytopathic changes in primary turkey kidney cell cultures but did not affect embryonating chicken eggs. Concentrated viral suspensions induced precipitin lines in agar gel immunodiffusion tests with known antisera against known turkey adenoviruses but did not show an antigenic relationship to chicken adenoviruses.", "contents": "Pathology of adenoviral infection in turkeys (Meleagris gallopavo) with respiratory disease and colisepticemia. Nuclear inclusion bodies typical of the adenovirus group were widespread in in the spleen and other tissues of 8-week-old turkeys with severe respiratory disease and concomitant evidence of colisepticemia. Adenoviral virions were seen in affected nuclei of splenic tissue and in negatively stained preparations of ground spleen. In splenic tissue, inclusions were most prominent in reticular cells and macrophages in the periarterial lymphoid sheaths, the red pulp and the marginal zones of the periarteriolar reticular sheaths. Marked reticuloendothelial hyperplasia, lymphoid atrophy and granulocytic splenitis characterized the splenic changes. There were inclusions in the respiratory tract, intestinal tract, liver, kidney and pancreas. Inoculation of young turkeys, especially when immunosuppressed, resulted in evidence of infection and respiratory disease. The viruses produced cytopathic changes in primary turkey kidney cell cultures but did not affect embryonating chicken eggs. Concentrated viral suspensions induced precipitin lines in agar gel immunodiffusion tests with known antisera against known turkey adenoviruses but did not show an antigenic relationship to chicken adenoviruses."}
{"id": "PMID:201076", "title": "Primary renal neoplasms of the dog.", "content": "Of 48 canine primary renal neoplasms found in the files of the Armed Forces Institute of Pathology, 36 were of tubular cell origin (five adenomas and 31 carcinomas), six of transitional cell origin (two papillomas and four carcinomas), two were nephroblastomas and four were nonepithelial. With the exception of nephroblastomas, renal neoplasms occurred in dogs older than 5 years and were most common in males. No breed predilection was apparent. Eight of the neoplasms were classified by histologic criteria as benign and 40 as malignant. Seventeen of the malignant neoplasms had metastasized. The neoplasms of tubular cell origin contained solid, tubular and papillary patterns, often mixed within the same tumor.", "contents": "Primary renal neoplasms of the dog. Of 48 canine primary renal neoplasms found in the files of the Armed Forces Institute of Pathology, 36 were of tubular cell origin (five adenomas and 31 carcinomas), six of transitional cell origin (two papillomas and four carcinomas), two were nephroblastomas and four were nonepithelial. With the exception of nephroblastomas, renal neoplasms occurred in dogs older than 5 years and were most common in males. No breed predilection was apparent. Eight of the neoplasms were classified by histologic criteria as benign and 40 as malignant. Seventeen of the malignant neoplasms had metastasized. The neoplasms of tubular cell origin contained solid, tubular and papillary patterns, often mixed within the same tumor."}
{"id": "PMID:201083", "title": "[Pathomorphology of infectious bursitis in chicks].", "content": "Morphologic studies were carried out on birds aged 17 to 90 days, affected with Gumboro disease and occasionally died from the same disease (infectious bursitis). Established were hemorrhages in the leg and breast musculature, substantial enlargement of the bursa of Fabricius, and lesions in the kidneys. In some cases hemorrhages were also found on the serous membrane of the parenchymal organs. The histologic investigation of the involved parenchymal organs revealed necrobiotic changes (karyopycnosis, karyorrhexis) in the cellular elements, which were evaluated as a possible diagnostic symptom. Discussed is the problem of the dynamics of the morphologic changes observed in the bursa of Fabricius in view of their differential-diagnostic value.", "contents": "[Pathomorphology of infectious bursitis in chicks]. Morphologic studies were carried out on birds aged 17 to 90 days, affected with Gumboro disease and occasionally died from the same disease (infectious bursitis). Established were hemorrhages in the leg and breast musculature, substantial enlargement of the bursa of Fabricius, and lesions in the kidneys. In some cases hemorrhages were also found on the serous membrane of the parenchymal organs. The histologic investigation of the involved parenchymal organs revealed necrobiotic changes (karyopycnosis, karyorrhexis) in the cellular elements, which were evaluated as a possible diagnostic symptom. Discussed is the problem of the dynamics of the morphologic changes observed in the bursa of Fabricius in view of their differential-diagnostic value."}
{"id": "PMID:201099", "title": "[RNA-synthesizing complex of the Sendai virus in the nucleoli of infected Erlich ascitic carcinoma cells].", "content": "A virus-specific complex with sedimentation constant of 250S and buoyant density 1.35 g/cm3 in cesium chloride density gradient is formed within 20--24 hours after infection in nucleoli of Ehrlich ascitic carcinoma cells infected with Sendai virus. The complex contains a rapidly sedimenting RNA (70--90S) which is about 50% stable to RN-ase. The complex has RNA-polymerase activity in a cell-free system; the product of the RNA-polymerase reaction is a RNA with sedimentation constant 50S. It is suggested that the virus-specific structure with sedimentation constant 250 S found in nucleoli is the Sendai virus replicative complex.", "contents": "[RNA-synthesizing complex of the Sendai virus in the nucleoli of infected Erlich ascitic carcinoma cells]. A virus-specific complex with sedimentation constant of 250S and buoyant density 1.35 g/cm3 in cesium chloride density gradient is formed within 20--24 hours after infection in nucleoli of Ehrlich ascitic carcinoma cells infected with Sendai virus. The complex contains a rapidly sedimenting RNA (70--90S) which is about 50% stable to RN-ase. The complex has RNA-polymerase activity in a cell-free system; the product of the RNA-polymerase reaction is a RNA with sedimentation constant 50S. It is suggested that the virus-specific structure with sedimentation constant 250 S found in nucleoli is the Sendai virus replicative complex."}
{"id": "PMID:201101", "title": "[Study of Sendai virus proteins: the proteolytic activity in the composition of the viral particles].", "content": "Disruption of virions with non-ionic detergent induced cleavage of virus proteins in purified preparations of Sendai virus. The proteolytic activity was detected in fraction of both the soluble proteins and subvirus particles. In the fraction of soluble proteins which initially had contained glycoproteins of the viral external envelope--HN and F--, both proteins were cleaved at a different relative rate. In parallel with polypeptide cleavage, the hemagglutinating and neuraminidase activity of the analysed specimens decreased. In the fraction of subvirus particles, sequential cleavage of inner virion proteins, P, m1, M, and NP, was observed, and also the formation of certain classes of intermediate products which had two typical features; (1) the products retained their connection with subvirus particles, and (2) the products of hydrolysis of the major structural proteins of the internal virus ribonucleoprotein, --P and NP--, had the electrophoretic motility similar to that of minor components, m2--m5. These observations demonstrate the principal possibility of the origin of some minor Sendai virus proteins as a result of degradation of major virus proteins.", "contents": "[Study of Sendai virus proteins: the proteolytic activity in the composition of the viral particles]. Disruption of virions with non-ionic detergent induced cleavage of virus proteins in purified preparations of Sendai virus. The proteolytic activity was detected in fraction of both the soluble proteins and subvirus particles. In the fraction of soluble proteins which initially had contained glycoproteins of the viral external envelope--HN and F--, both proteins were cleaved at a different relative rate. In parallel with polypeptide cleavage, the hemagglutinating and neuraminidase activity of the analysed specimens decreased. In the fraction of subvirus particles, sequential cleavage of inner virion proteins, P, m1, M, and NP, was observed, and also the formation of certain classes of intermediate products which had two typical features; (1) the products retained their connection with subvirus particles, and (2) the products of hydrolysis of the major structural proteins of the internal virus ribonucleoprotein, --P and NP--, had the electrophoretic motility similar to that of minor components, m2--m5. These observations demonstrate the principal possibility of the origin of some minor Sendai virus proteins as a result of degradation of major virus proteins."}
{"id": "PMID:201106", "title": "[Long-time follow-up of rare liver tumours in infancy (author's transl)].", "content": "Two rarely-observed tumours of the liver are discussed: firstly, primary liver carcinoma in a 5-month-old infant, and secondly, myxoma in a newborn infant. Both tumours were removed surgically. The child with primary liver cell carcinoma was treated for 2 1/2 years with cyclophosphamide. She has been followed-up for 8 years and can be assumed to be cured. Both children developed normally. The pathogenesis of liver tumours at this early age is discussed.", "contents": "[Long-time follow-up of rare liver tumours in infancy (author's transl)]. Two rarely-observed tumours of the liver are discussed: firstly, primary liver carcinoma in a 5-month-old infant, and secondly, myxoma in a newborn infant. Both tumours were removed surgically. The child with primary liver cell carcinoma was treated for 2 1/2 years with cyclophosphamide. She has been followed-up for 8 years and can be assumed to be cured. Both children developed normally. The pathogenesis of liver tumours at this early age is discussed."}
{"id": "PMID:201102", "title": "[Reproduction, morphogenesis and immunobiological properties of Aujeszky's disease virus commercially cultured in a suspension of poultry embryo explants].", "content": "The results of the study of reproduction, morphogenesis, and immunogenic properties of Aujeszky's disease virus (ADV) cultivated on an industrial scale in chick, duck and quail embryo explant suspensions are presented. A method for production of vaccine and virulent ADV strains with the activity of at least 7.5 log TCD50/ML in tanks of 5, 50, and 100 1 capacity was developed. A relationship between virion morphology and duration of cultivation was established. For ADV cultivated for 70 hours, a direct relationship between infectivity and immunogenicity was demonstrated.", "contents": "[Reproduction, morphogenesis and immunobiological properties of Aujeszky's disease virus commercially cultured in a suspension of poultry embryo explants]. The results of the study of reproduction, morphogenesis, and immunogenic properties of Aujeszky's disease virus (ADV) cultivated on an industrial scale in chick, duck and quail embryo explant suspensions are presented. A method for production of vaccine and virulent ADV strains with the activity of at least 7.5 log TCD50/ML in tanks of 5, 50, and 100 1 capacity was developed. A relationship between virion morphology and duration of cultivation was established. For ADV cultivated for 70 hours, a direct relationship between infectivity and immunogenicity was demonstrated."}
{"id": "PMID:201103", "title": "[Importance of the results of a virological examination of sewage. A comparison of the series of enteroviruses isolated from sewage and from the feces of virus excreters].", "content": "Simultaneous examinations for the presence of enteroviruses were carried out on sewage of the central aeration station, periferal collectors of the most populous institutions, preschool children's institutions as well as feces of children attending these institutions in a community of urban type. A high degree of coincidence of spectra of enteroviruses isolated from sewage of the central station, periferal collectors, sewage of children's institutions, and from the feces of most virus excretors was demonstrated. No enteroviruses found in occasional virus excretors were detected in sewage. Enteroviruses were regularly found in sewage of periferal collectors if approximately 10% of children excreted a certain virus type simultaneously.", "contents": "[Importance of the results of a virological examination of sewage. A comparison of the series of enteroviruses isolated from sewage and from the feces of virus excreters]. Simultaneous examinations for the presence of enteroviruses were carried out on sewage of the central aeration station, periferal collectors of the most populous institutions, preschool children's institutions as well as feces of children attending these institutions in a community of urban type. A high degree of coincidence of spectra of enteroviruses isolated from sewage of the central station, periferal collectors, sewage of children's institutions, and from the feces of most virus excretors was demonstrated. No enteroviruses found in occasional virus excretors were detected in sewage. Enteroviruses were regularly found in sewage of periferal collectors if approximately 10% of children excreted a certain virus type simultaneously."}
{"id": "PMID:201108", "title": "[Collagenase activity in an animal and a human carcinoma (author's transl)].", "content": "High amounts of collagenase were found in chemically-induced carcinomas of the mouse skin and in carcinomas of the human urinary bladder. Part of the total enzyme activity was detected in the supernatant after sedimentation of the tumour homogenate at 6000 x g and dialysis for 48 hours. The remainder was extracted from the pellet by the use of 5 M urea. Though the localization of enzyme production and regulation of enzyme activity is still unclear, the collagenases may be implicated in the breakdown of collagen structures during tumour invasion.", "contents": "[Collagenase activity in an animal and a human carcinoma (author's transl)]. High amounts of collagenase were found in chemically-induced carcinomas of the mouse skin and in carcinomas of the human urinary bladder. Part of the total enzyme activity was detected in the supernatant after sedimentation of the tumour homogenate at 6000 x g and dialysis for 48 hours. The remainder was extracted from the pellet by the use of 5 M urea. Though the localization of enzyme production and regulation of enzyme activity is still unclear, the collagenases may be implicated in the breakdown of collagen structures during tumour invasion."}
{"id": "PMID:201107", "title": "[Herpes simplex virus (hsv-1 and hsv-2) infection: its clinical and oncogenic properties (author's transl)].", "content": "The epidemiology and clinical features of diseases caused by the herpes simplex virus, are reviewed and recent results are discussed which give an insight into the complex mechanism of primary and chronic, recurrent HSV-1 infections. Immunological reactions in HSV infection and data concerning the oncogenic potential of HSV-1 and -2 are dealt with. Furthermore, current therapeutic possibilities are outlined.", "contents": "[Herpes simplex virus (hsv-1 and hsv-2) infection: its clinical and oncogenic properties (author's transl)]. The epidemiology and clinical features of diseases caused by the herpes simplex virus, are reviewed and recent results are discussed which give an insight into the complex mechanism of primary and chronic, recurrent HSV-1 infections. Immunological reactions in HSV infection and data concerning the oncogenic potential of HSV-1 and -2 are dealt with. Furthermore, current therapeutic possibilities are outlined."}
{"id": "PMID:201104", "title": "[Importance of the results of a virological examination of sewage. A quantitative evaluation of the finding of enteroviruses in sewage].", "content": "In order to evaluate quantitatively the effectiveness of virological examinations of sewage, a labeled virus in a dose of 7.5X10(9) PFU was introduced into the canalization system of a community. Such an amount of virus could be found in the canalization system if 5--10% of the residents would excrete it simultaneously. The labeled virus was selectively detected in the community sewage. This procedure has demonstrated that the routine methods for sewage collection, specimen treatment, and virus isolation permit virus detection when 5--10% of this virus excretors are available. The labeled virus entered the canalization system most actively within the first 2 hours after administration, then its amount declined, and within 24 hours ceased. The labeled virus was found on all swabs which were in the sewage flow since the time of administration to the 7th day. The maximum amount of virus was found on the swab which was in the sewage flow for the first 2 hours after virus administration. By 7 days the amount of labeled virus on swabs decreased 10-fold. Under experimental conditions, in sewage kept at 25 degrees C enteroviruses of the group of poliomyelitis, ECHO, and Coxsackie had approximately similar inactivation rate (0.16--0.22 Ig TCD50 per day) and the half-life period (1.3 days), that is, in 7 days the virus titer on a swab should decline by 1.0--1.5 Ig TCD50.", "contents": "[Importance of the results of a virological examination of sewage. A quantitative evaluation of the finding of enteroviruses in sewage]. In order to evaluate quantitatively the effectiveness of virological examinations of sewage, a labeled virus in a dose of 7.5X10(9) PFU was introduced into the canalization system of a community. Such an amount of virus could be found in the canalization system if 5--10% of the residents would excrete it simultaneously. The labeled virus was selectively detected in the community sewage. This procedure has demonstrated that the routine methods for sewage collection, specimen treatment, and virus isolation permit virus detection when 5--10% of this virus excretors are available. The labeled virus entered the canalization system most actively within the first 2 hours after administration, then its amount declined, and within 24 hours ceased. The labeled virus was found on all swabs which were in the sewage flow since the time of administration to the 7th day. The maximum amount of virus was found on the swab which was in the sewage flow for the first 2 hours after virus administration. By 7 days the amount of labeled virus on swabs decreased 10-fold. Under experimental conditions, in sewage kept at 25 degrees C enteroviruses of the group of poliomyelitis, ECHO, and Coxsackie had approximately similar inactivation rate (0.16--0.22 Ig TCD50 per day) and the half-life period (1.3 days), that is, in 7 days the virus titer on a swab should decline by 1.0--1.5 Ig TCD50."}
{"id": "PMID:201111", "title": "[D-thyroxin in the therapy of type IIa and IIb hyperlipoproteinemias].", "content": "21 patients with hyperlipoproteinaemias of type IIa and IIb were treated with D-thyroxin (4 mg/die) after a placebo phase. The observed changes of the cholesterol and triglyceride level in the serum are described. Hypermetabolic and cardiac side effects did not appear in the patients. The possible sites of action of D-thyroxin in the intermediary lipid metabolism are discussed.", "contents": "[D-thyroxin in the therapy of type IIa and IIb hyperlipoproteinemias]. 21 patients with hyperlipoproteinaemias of type IIa and IIb were treated with D-thyroxin (4 mg/die) after a placebo phase. The observed changes of the cholesterol and triglyceride level in the serum are described. Hypermetabolic and cardiac side effects did not appear in the patients. The possible sites of action of D-thyroxin in the intermediary lipid metabolism are discussed."}
{"id": "PMID:201105", "title": "[Methods for the rapid diagnosis of herpes simplex using the indirect hemagglutination reaction].", "content": "A method for preparation of an erythrocyte immunoglobulin herpes preparation for the indirect hemagglutination test (IHA) is described. A high specificity and sensitivity of this test and the preparation has been demonstrated. The results of the use of IHA with this preparation for the detection of herpes simplex virus in specimens from patients are presented.", "contents": "[Methods for the rapid diagnosis of herpes simplex using the indirect hemagglutination reaction]. A method for preparation of an erythrocyte immunoglobulin herpes preparation for the indirect hemagglutination test (IHA) is described. A high specificity and sensitivity of this test and the preparation has been demonstrated. The results of the use of IHA with this preparation for the detection of herpes simplex virus in specimens from patients are presented."}
{"id": "PMID:201112", "title": "[Tracer kinetic studies of the cholesterol metabolism in patients with hypercholesterolemia].", "content": "For the examination of the cholesterol metabolism in patients with normal and increased serum cholesterol the 3H-cholesterol was used. The tracer-kinetic investigation programme consisted of the examination of the serum for free and esterified cholesterol as well as the separation in VLDL-, LDL- AND HDL-fractions. The establishment of the content of radioactivity of the individual samples was carried out in the LSC-nitrobeta 1210. Specific activity-time-curves were established and fitted according to a mathematical programme. The most essential findings of the evaluation of these curves resulted in a clearly changed turnover of the LDL-fraction. Possible causes for the disturbed LDL-turnover were discussed.", "contents": "[Tracer kinetic studies of the cholesterol metabolism in patients with hypercholesterolemia]. For the examination of the cholesterol metabolism in patients with normal and increased serum cholesterol the 3H-cholesterol was used. The tracer-kinetic investigation programme consisted of the examination of the serum for free and esterified cholesterol as well as the separation in VLDL-, LDL- AND HDL-fractions. The establishment of the content of radioactivity of the individual samples was carried out in the LSC-nitrobeta 1210. Specific activity-time-curves were established and fitted according to a mathematical programme. The most essential findings of the evaluation of these curves resulted in a clearly changed turnover of the LDL-fraction. Possible causes for the disturbed LDL-turnover were discussed."}
{"id": "PMID:201114", "title": "Virion antigens introduced exogeneously into the cell membrane render syngeneic target cells susceptible for T cell-mediated cytolysis.", "content": "Non-infectious sendai virus renders H-2 matched target cells susceptible to the lytic effect of sendai virus immune cytotoxic T lymphocytes. This observation suggests that exogeneous insertion of virion antigen in the membrane of the target cell is sufficient for T cell cytotoxicity. The finding is incompatible with the concept that H-2K or H-2D gene products of the target cells must be altered in their primary structure (pretranslational effect of the virus infection) for T cell-mediated cytolysis to occur.", "contents": "Virion antigens introduced exogeneously into the cell membrane render syngeneic target cells susceptible for T cell-mediated cytolysis. Non-infectious sendai virus renders H-2 matched target cells susceptible to the lytic effect of sendai virus immune cytotoxic T lymphocytes. This observation suggests that exogeneous insertion of virion antigen in the membrane of the target cell is sufficient for T cell cytotoxicity. The finding is incompatible with the concept that H-2K or H-2D gene products of the target cells must be altered in their primary structure (pretranslational effect of the virus infection) for T cell-mediated cytolysis to occur."}
{"id": "PMID:201115", "title": "Enzyme histochemistry of cultured ovarian cells. II. Histochemistry of porcine theca interna cells in tissue culture.", "content": "By means of histochemical technique the activities of delta53beta-, 17beta-, 20alpha-hydroxysteroid dehydrogenases and glucose-6-phosphate dehydrogenase, as well as alkaline and acid phosphatase were investigated in monolayer cultures of theca interna cells, isolated from preovulatory porcine ovarian follicles. It was found that theca interna cells exhibited high and constant activity of delta53beta-hydroxysteroid dehydrogenase and G6P-DH, whereas activities of both 17beta- and 20alpha-hydroxysteroid dehydrogenase were lower and showed some fluctuations during in vitro culture. Addition of LH to the medium brought about the increase of all studied dehydrogenases. FSH was less effective. Estradiol showed quite and inhibiting effect. All the hormones mentioned above caused the increase of alkaline and acid phosphatase activity in cultured porcine theca interna cells.", "contents": "Enzyme histochemistry of cultured ovarian cells. II. Histochemistry of porcine theca interna cells in tissue culture. By means of histochemical technique the activities of delta53beta-, 17beta-, 20alpha-hydroxysteroid dehydrogenases and glucose-6-phosphate dehydrogenase, as well as alkaline and acid phosphatase were investigated in monolayer cultures of theca interna cells, isolated from preovulatory porcine ovarian follicles. It was found that theca interna cells exhibited high and constant activity of delta53beta-hydroxysteroid dehydrogenase and G6P-DH, whereas activities of both 17beta- and 20alpha-hydroxysteroid dehydrogenase were lower and showed some fluctuations during in vitro culture. Addition of LH to the medium brought about the increase of all studied dehydrogenases. FSH was less effective. Estradiol showed quite and inhibiting effect. All the hormones mentioned above caused the increase of alkaline and acid phosphatase activity in cultured porcine theca interna cells."}
{"id": "PMID:201116", "title": "[Size, structure, and dynamics of bile salt/lecithin mixed micelles (author's transl)].", "content": "The structure and size of lecithin/sodium glycocholate mixed micelles was investigated by quasi-elastic laser light scattering and spin label techniques. The investigations are in accordance with a bilayer model for these micelles. The order parameter and the phase transition enthalpy of the micellar bilayer were determined. The lateral and rotational diffusion constants of label molecules are compared with the corresponding diffusion constants in liposomes.", "contents": "[Size, structure, and dynamics of bile salt/lecithin mixed micelles (author's transl)]. The structure and size of lecithin/sodium glycocholate mixed micelles was investigated by quasi-elastic laser light scattering and spin label techniques. The investigations are in accordance with a bilayer model for these micelles. The order parameter and the phase transition enthalpy of the micellar bilayer were determined. The lateral and rotational diffusion constants of label molecules are compared with the corresponding diffusion constants in liposomes."}
{"id": "PMID:201118", "title": "P1, P5-Bis-(5'-adenosyl)pentaphosphate: is this adenylate kinase inhibitor substrate for mitochondrial processes?", "content": "1. P1, P5-Bis-(5'-adenosyl) pentaphosphate (AP5-A) inhibits \"soluble\" adenylate kinase even when this enzyme is an integral part of the complete mitochondrion. The Ki is 10(-5) M, i.e. about two orders of magnitude higher than the inhibitor contants determined for the purified adenylate kinase of rabbit muscle and an enzyme preparation separated from the mitochondrial intermembrane space. The weaker inhibitory effect is due to a lower accessibility of the enzyme. 2. as to be expected Ap5A which is of the \"multisubstrate analogue\"-type does not affect mitochondrial nucleoside diphosphate kinase. 3. Though Ap5A owns the structural elements of both ATP and ADP it is not a substrate of the adenine nucleotide carrier, i.e. neither it is exchanged across the inner mitochondrial membrane nor speicifically bound. 4. Ap5A is not metabolized by rat liver mitochondria.", "contents": "P1, P5-Bis-(5'-adenosyl)pentaphosphate: is this adenylate kinase inhibitor substrate for mitochondrial processes? 1. P1, P5-Bis-(5'-adenosyl) pentaphosphate (AP5-A) inhibits \"soluble\" adenylate kinase even when this enzyme is an integral part of the complete mitochondrion. The Ki is 10(-5) M, i.e. about two orders of magnitude higher than the inhibitor contants determined for the purified adenylate kinase of rabbit muscle and an enzyme preparation separated from the mitochondrial intermembrane space. The weaker inhibitory effect is due to a lower accessibility of the enzyme. 2. as to be expected Ap5A which is of the \"multisubstrate analogue\"-type does not affect mitochondrial nucleoside diphosphate kinase. 3. Though Ap5A owns the structural elements of both ATP and ADP it is not a substrate of the adenine nucleotide carrier, i.e. neither it is exchanged across the inner mitochondrial membrane nor speicifically bound. 4. Ap5A is not metabolized by rat liver mitochondria."}
{"id": "PMID:201119", "title": "Chirality of the Hydrogen transfer to NAD catalyzed by (3R) hydroxybutyrate dehydrogenase from Pseudomonas lemoignei.", "content": "The chirality of the hydrogen transfer from (3R) hydroxybutyrate to NAD catalyzed by (3R)hydroxybutyrate dehydrogenase (E.C. 1.1.1.30, D-3-hydroxybutyrate : NAD oxidoreductase) from Pseudomonas lemoignei was investigated. [4(-3)H] NAD was enzymatically reduced to (4R) [4(-3)H]NADH with (3RS) hydroxybutyrate. This observation was confirmed since NAD could be reduced to (4S) [4(-3)H] NADH with (3RS) [3(-3)H] hydroxybutyrate and (3R) hydroxybutyrate dehydrogenase. From these experiments it can be concluded that (3R) hydroxybutyrate dehydrogenase from P. lemoignei should be classified as an B or (S) type dehydrogenase.", "contents": "Chirality of the Hydrogen transfer to NAD catalyzed by (3R) hydroxybutyrate dehydrogenase from Pseudomonas lemoignei. The chirality of the hydrogen transfer from (3R) hydroxybutyrate to NAD catalyzed by (3R)hydroxybutyrate dehydrogenase (E.C. 1.1.1.30, D-3-hydroxybutyrate : NAD oxidoreductase) from Pseudomonas lemoignei was investigated. [4(-3)H] NAD was enzymatically reduced to (4R) [4(-3)H]NADH with (3RS) hydroxybutyrate. This observation was confirmed since NAD could be reduced to (4S) [4(-3)H] NADH with (3RS) [3(-3)H] hydroxybutyrate and (3R) hydroxybutyrate dehydrogenase. From these experiments it can be concluded that (3R) hydroxybutyrate dehydrogenase from P. lemoignei should be classified as an B or (S) type dehydrogenase."}
{"id": "PMID:201128", "title": "[Serum-treatment in the rubella hi-test by menas of silicic acid (author's transl)].", "content": "The serum treatment for the removal of nonspecific inhibitors in the Rubella HI-test with silicic acid was investigated by means of isolated lipoproteins and after a micromethod by means of Sindbis-virus. Reduction of the three classes of lipoproteins after treatment with silicic acid was good. In the Sindbis HI-test only 2% of the sera showed low titers after treatment. The method proved to be a reliable tool as removal of unspecific inhibitory activity is concerned.", "contents": "[Serum-treatment in the rubella hi-test by menas of silicic acid (author's transl)]. The serum treatment for the removal of nonspecific inhibitors in the Rubella HI-test with silicic acid was investigated by means of isolated lipoproteins and after a micromethod by means of Sindbis-virus. Reduction of the three classes of lipoproteins after treatment with silicic acid was good. In the Sindbis HI-test only 2% of the sera showed low titers after treatment. The method proved to be a reliable tool as removal of unspecific inhibitory activity is concerned."}
{"id": "PMID:201124", "title": "[Plastic reorganization of the activity of sensorimotor cortex neurons during elaboration of a cellular analog of a temporary connection].", "content": "A study of plastic reorganizations of neuronal responses in the rabbit sensorimotor cortex was made on a cellular analogue of conditioned connection where stimulation of the ventrobasal thalamic complex (VBC) was used as a conditioned stimulus, while polarization of the cell through a recording microelectrode, as an unconditioned one. The responses of 60% of the studied neurones to the stimulation of the VBC showed significant plastic changes after the pairing of thalamic stimulation with polarization. The changes obtained met the criteria of identification of conditioned reactions. One of the possible mechanisms of the recorded plastic reorganizations of neuronal reactions consists in a selective increase in the effectiveness of excitatory synapses, whose subthreshold activation coincided with the cell activation. These data may be regarded as manifestation of a hypothetic reverse influence of neuronal discharges on the effectiveness of the synaptic transmission.", "contents": "[Plastic reorganization of the activity of sensorimotor cortex neurons during elaboration of a cellular analog of a temporary connection]. A study of plastic reorganizations of neuronal responses in the rabbit sensorimotor cortex was made on a cellular analogue of conditioned connection where stimulation of the ventrobasal thalamic complex (VBC) was used as a conditioned stimulus, while polarization of the cell through a recording microelectrode, as an unconditioned one. The responses of 60% of the studied neurones to the stimulation of the VBC showed significant plastic changes after the pairing of thalamic stimulation with polarization. The changes obtained met the criteria of identification of conditioned reactions. One of the possible mechanisms of the recorded plastic reorganizations of neuronal reactions consists in a selective increase in the effectiveness of excitatory synapses, whose subthreshold activation coincided with the cell activation. These data may be regarded as manifestation of a hypothetic reverse influence of neuronal discharges on the effectiveness of the synaptic transmission."}
{"id": "PMID:201129", "title": "[Ultrastructural study of lipopolysaccharide and of polymyxin B-induced changes of the outer membrane of Serratia marcescens (author's transl)].", "content": "Electron micrographs of lipopolysaccharide (LPS) from Serratia marcescens which have been extracted with phenol/water, suspended in dist. water and subsequently negatively stained reveale round to ovoid particles besides singular ribbon-like structures. These structures are interpreted as collapsed LPS-strands of the outer membrane (OM). Fine structure investigations were carried out on strand-like structures which had been obtained by light alcalization of the particle suspension. Partial denaturation of LPS in ethylene-diaminotetracetic acid with polymyxin B (PB) gave rise to broad bends with periodic 180 degrees-torsions, indicating a helical structure. Chemically fixed LPS in phosphate buffer which were only partial transformed into LPS-strands, additionally revealed that a given LPS-strand consists of two electron-microscopic identical sub-strands which form a double helix. After short times of exposure to PB, negatively stained cells of Serratia marcescens show strand-like cell wall components on the cell surface consisting of longitudinal fibrils. In a further stage of denaturation, the strand-like structures form \"projections\" of the OM or are completely loosened. Based on a helical arrangement in the negative staining preparations as well as in the thin sections, they are identified as LPS-strands. Presumably, the LPS in the OM exists as contiguous strains. The development of the \"double track\"-aspect of the LPS in thin sections may be explained as a result of the projections of the helical longitudinal fibrils into the image plane.", "contents": "[Ultrastructural study of lipopolysaccharide and of polymyxin B-induced changes of the outer membrane of Serratia marcescens (author's transl)]. Electron micrographs of lipopolysaccharide (LPS) from Serratia marcescens which have been extracted with phenol/water, suspended in dist. water and subsequently negatively stained reveale round to ovoid particles besides singular ribbon-like structures. These structures are interpreted as collapsed LPS-strands of the outer membrane (OM). Fine structure investigations were carried out on strand-like structures which had been obtained by light alcalization of the particle suspension. Partial denaturation of LPS in ethylene-diaminotetracetic acid with polymyxin B (PB) gave rise to broad bends with periodic 180 degrees-torsions, indicating a helical structure. Chemically fixed LPS in phosphate buffer which were only partial transformed into LPS-strands, additionally revealed that a given LPS-strand consists of two electron-microscopic identical sub-strands which form a double helix. After short times of exposure to PB, negatively stained cells of Serratia marcescens show strand-like cell wall components on the cell surface consisting of longitudinal fibrils. In a further stage of denaturation, the strand-like structures form \"projections\" of the OM or are completely loosened. Based on a helical arrangement in the negative staining preparations as well as in the thin sections, they are identified as LPS-strands. Presumably, the LPS in the OM exists as contiguous strains. The development of the \"double track\"-aspect of the LPS in thin sections may be explained as a result of the projections of the helical longitudinal fibrils into the image plane."}
{"id": "PMID:201133", "title": "Cytomegalovirus hepatitis (diagnosis and differential diagnosis).", "content": "In a 12-year-old female patients with HBAg phi hepatitis a differential diagnosis of the diseases has been considered. The CMV etiology of the hepatitis was suspected on the basis of a persistent temperature, hepatomegaly, a mild icterus, enlarged glands in the neck, predominantly mononuclear cells in the peripheral blood, a negative Paul-Bunnell test, and insufficiently characteristic biochemical analyses for virus A hepatitis. The CMV etiology of the disease was virologically confirmed. On the basis of the clinical picture without virological results, the diagnosis could not have been made with certainty.", "contents": "Cytomegalovirus hepatitis (diagnosis and differential diagnosis). In a 12-year-old female patients with HBAg phi hepatitis a differential diagnosis of the diseases has been considered. The CMV etiology of the hepatitis was suspected on the basis of a persistent temperature, hepatomegaly, a mild icterus, enlarged glands in the neck, predominantly mononuclear cells in the peripheral blood, a negative Paul-Bunnell test, and insufficiently characteristic biochemical analyses for virus A hepatitis. The CMV etiology of the disease was virologically confirmed. On the basis of the clinical picture without virological results, the diagnosis could not have been made with certainty."}
{"id": "PMID:201134", "title": "Effect of salicylates on cyclic AMP in isolated rat gastric mucosa.", "content": "Studies on the cyclic AMP content of isolated rat gastric mucosa have been conducted with sodium salicylate and lysine-acetylsalicylate singly and combined with gastric secretagogues and their antagonists. Both salicylates at a concentration of 1.66 X 10(-2) M increased the amount of cyclic AMP. The increase of gastric mucosal cyclic AMP produced by sodium salicylate was diminished by prostaglandin E1 (10(-5) M), atropine (10(-6) M) and the H2-antihistamine metiamide (2 X 10(-4) M). Theophylline 3 X 10(-3) M), histamine (10(-3) M) and pentagastrin (10(-6) M) did not enhance the cyclic-AMP-response to salicylate or lysine-acetyl-salicylate.", "contents": "Effect of salicylates on cyclic AMP in isolated rat gastric mucosa. Studies on the cyclic AMP content of isolated rat gastric mucosa have been conducted with sodium salicylate and lysine-acetylsalicylate singly and combined with gastric secretagogues and their antagonists. Both salicylates at a concentration of 1.66 X 10(-2) M increased the amount of cyclic AMP. The increase of gastric mucosal cyclic AMP produced by sodium salicylate was diminished by prostaglandin E1 (10(-5) M), atropine (10(-6) M) and the H2-antihistamine metiamide (2 X 10(-4) M). Theophylline 3 X 10(-3) M), histamine (10(-3) M) and pentagastrin (10(-6) M) did not enhance the cyclic-AMP-response to salicylate or lysine-acetyl-salicylate."}
{"id": "PMID:201135", "title": "[Nasopharyngeal angiofibroma. Histochemical observations and hormone therapy (author's transl)].", "content": "There were carried out substrate- and enzymhistochemical reactions of the typical nasopharyngeal angiofibroma in 6 cases. In the environs of the vessels there were mainly neutral mucopolysaccharides, in the left intercellular substance and in the fibroblasts and most cells acid carbohydrates were found. The protein reactions pointed out a conspicouos strong contents of alkaline proteins in fibroblasts, mast cells and vessel environs. In the mast cells and fibroblasts tryptophan was found plentifully, in fibroblasts and vessel environs a lot of tyrosin was provable. The alakline phosphatase was traceable in fibroblasts and mast cells with great intensity. Strong reactivities of the acid phosphatases in all of the cells of the tissue refer to intensive lysosomal activities and considerable secretion transactions. The reaction of LDH as a representative of energy metabolism settles down in all of the cells and vessel environs in a strong way. The histochemical examination of a preparation of the naso-pharyngeal angiofibroma after hormone therapy showed a falling out of all the enzyme activities. The reduction of the acid phosphatases seems to be of special importance. Substrathistochemically there weren't any clear modifications concerning quality and quantity. A comparatively examined separation of an ordinary fibroma of the nasopharynx indicated similar enzymhistochemical pictures disregard the intensive reaction of the unspecific esterase, which doesn't appear concerning the nasopharyngeal angiofibroma. The carbohydrate reactions demonstrated some differences to the typical nasopharyngeal angiofibroma.", "contents": "[Nasopharyngeal angiofibroma. Histochemical observations and hormone therapy (author's transl)]. There were carried out substrate- and enzymhistochemical reactions of the typical nasopharyngeal angiofibroma in 6 cases. In the environs of the vessels there were mainly neutral mucopolysaccharides, in the left intercellular substance and in the fibroblasts and most cells acid carbohydrates were found. The protein reactions pointed out a conspicouos strong contents of alkaline proteins in fibroblasts, mast cells and vessel environs. In the mast cells and fibroblasts tryptophan was found plentifully, in fibroblasts and vessel environs a lot of tyrosin was provable. The alakline phosphatase was traceable in fibroblasts and mast cells with great intensity. Strong reactivities of the acid phosphatases in all of the cells of the tissue refer to intensive lysosomal activities and considerable secretion transactions. The reaction of LDH as a representative of energy metabolism settles down in all of the cells and vessel environs in a strong way. The histochemical examination of a preparation of the naso-pharyngeal angiofibroma after hormone therapy showed a falling out of all the enzyme activities. The reduction of the acid phosphatases seems to be of special importance. Substrathistochemically there weren't any clear modifications concerning quality and quantity. A comparatively examined separation of an ordinary fibroma of the nasopharynx indicated similar enzymhistochemical pictures disregard the intensive reaction of the unspecific esterase, which doesn't appear concerning the nasopharyngeal angiofibroma. The carbohydrate reactions demonstrated some differences to the typical nasopharyngeal angiofibroma."}
{"id": "PMID:201136", "title": "Dry weight, triglycerides content and glucose-6-phosphatase activity of hepatocytes separated by sedimentation.", "content": "1) Isolated rat-hepatocytes were subfractionated by isopycnic or velocity sedimentation, and dry mass, triglycerides content and Glucose-6-Phosphatase activity of different subpopulations were determined. 2) Distribution of the cell dry masses and dry mass per average cell were substantially similar in all the fractions separated by isopycnic sedimentation. Velocity sedimentation allowed a satisfactory separation of cells of different dry mass. 3) Triglycerides content and Glucose-6-Phosphatase activity of cells of the different fractions obtained by isopycnic sedimentation showed no statistically significant difference. Subpopulations fractionated by velocity sedimentation differed in both triglycerides content and Glucose-6-Phosphatase activity, which were substantially parallel to the cell dry mass.", "contents": "Dry weight, triglycerides content and glucose-6-phosphatase activity of hepatocytes separated by sedimentation. 1) Isolated rat-hepatocytes were subfractionated by isopycnic or velocity sedimentation, and dry mass, triglycerides content and Glucose-6-Phosphatase activity of different subpopulations were determined. 2) Distribution of the cell dry masses and dry mass per average cell were substantially similar in all the fractions separated by isopycnic sedimentation. Velocity sedimentation allowed a satisfactory separation of cells of different dry mass. 3) Triglycerides content and Glucose-6-Phosphatase activity of cells of the different fractions obtained by isopycnic sedimentation showed no statistically significant difference. Subpopulations fractionated by velocity sedimentation differed in both triglycerides content and Glucose-6-Phosphatase activity, which were substantially parallel to the cell dry mass."}
{"id": "PMID:201137", "title": "Fine structural localization of glucose-6-phosphatase activity in the pancreatic islets of two amphibian species (Salamandra salamandra L. and Rana esculenta L.).", "content": "The ultrastructural distribution of glucose-6-phosphatase activity has been investigated in the salamander and frog pancreas. In the pancreas of salamander the enzyme was located in the A-cells, while in frog it occurred in all main types of islet cells B-, A-, and D-cells). As a rule, the reaction intensity was higher in the frog islet cells. No reaction was recorded in the exocrine pancreatic tissue of both species. The glucose-6-phosphatase activity was constantly detected in the lumen of rough endoplasmic reticulum and between the nuclear envelopes. Other enzyme localizations, observed especially in the A-cells of the salamander pancreas, were considered possible diffusion artifacts ro remnants of other phosphatase activity. The enzyme distribution in different types of islet cells, as well as its functional significance are discussed in relation to the findings of other authors.", "contents": "Fine structural localization of glucose-6-phosphatase activity in the pancreatic islets of two amphibian species (Salamandra salamandra L. and Rana esculenta L.). The ultrastructural distribution of glucose-6-phosphatase activity has been investigated in the salamander and frog pancreas. In the pancreas of salamander the enzyme was located in the A-cells, while in frog it occurred in all main types of islet cells B-, A-, and D-cells). As a rule, the reaction intensity was higher in the frog islet cells. No reaction was recorded in the exocrine pancreatic tissue of both species. The glucose-6-phosphatase activity was constantly detected in the lumen of rough endoplasmic reticulum and between the nuclear envelopes. Other enzyme localizations, observed especially in the A-cells of the salamander pancreas, were considered possible diffusion artifacts ro remnants of other phosphatase activity. The enzyme distribution in different types of islet cells, as well as its functional significance are discussed in relation to the findings of other authors."}
{"id": "PMID:201139", "title": "The potency ratio of galanthamine and neostigmine on the reversal of the tubocurarine block in the isolated rat diaphragm.", "content": "The potency ratio of galanthamine and neostigmine was studied on the rat phrenic nerve-diaphragm preparation. This ratio appeared to be about 18 on a weight base. The potency ratio in man in vivo, is about 20. Hence we concluded that this potency ratio might mainly be due to the difference in potency on the neuromuscular transmission and not to kinetic differences.", "contents": "The potency ratio of galanthamine and neostigmine on the reversal of the tubocurarine block in the isolated rat diaphragm. The potency ratio of galanthamine and neostigmine was studied on the rat phrenic nerve-diaphragm preparation. This ratio appeared to be about 18 on a weight base. The potency ratio in man in vivo, is about 20. Hence we concluded that this potency ratio might mainly be due to the difference in potency on the neuromuscular transmission and not to kinetic differences."}
{"id": "PMID:201143", "title": "Demyelination in allergic and Marek's disease virus induced neuritis. Comparative electron microscopic studies.", "content": "Patterns of demyelination were studied in sciatic nerves, spinal roots and ganglia of chickens afflicted with either Marek's disease (MD) or experimental allergic neuritis (EAN). MD was induced in susceptible chicks after hatching by inoculation of the JM strain of MD Herpes virus. Tissues from these chickens were examined 7-83 days after infection. EAN was studied 10-21 days after sensitization of 4 week old chickens to emulsions containing human peripheral nerve with complete Freund's adjuvant. In both conditions lesions were encountered which consisted of perivenular infiltrates of mononuclear cells that penetrated the basal lamina of the neurolemmal sheath, displaced Schwann cells, lysed and stripped myelin lamellae without damage to axons. Other lesions in MD were characterized by lymphomatous infiltrates that contained necrotic cells and disintegrating axons. The similarity of the demyelinating process in MD to that seen in EAN suggests that MD virus infection activates lymphocytes sensitized to peripheral nerve myelin. The findings are discussed with reference to acute idiopathic polyneuritis (Guillain-Barr\u00e9 syndrome) in patients with preceding or concurrent Herpes virus infections including those known to cause lymphoproliferative disorders.", "contents": "Demyelination in allergic and Marek's disease virus induced neuritis. Comparative electron microscopic studies. Patterns of demyelination were studied in sciatic nerves, spinal roots and ganglia of chickens afflicted with either Marek's disease (MD) or experimental allergic neuritis (EAN). MD was induced in susceptible chicks after hatching by inoculation of the JM strain of MD Herpes virus. Tissues from these chickens were examined 7-83 days after infection. EAN was studied 10-21 days after sensitization of 4 week old chickens to emulsions containing human peripheral nerve with complete Freund's adjuvant. In both conditions lesions were encountered which consisted of perivenular infiltrates of mononuclear cells that penetrated the basal lamina of the neurolemmal sheath, displaced Schwann cells, lysed and stripped myelin lamellae without damage to axons. Other lesions in MD were characterized by lymphomatous infiltrates that contained necrotic cells and disintegrating axons. The similarity of the demyelinating process in MD to that seen in EAN suggests that MD virus infection activates lymphocytes sensitized to peripheral nerve myelin. The findings are discussed with reference to acute idiopathic polyneuritis (Guillain-Barr\u00e9 syndrome) in patients with preceding or concurrent Herpes virus infections including those known to cause lymphoproliferative disorders."}
{"id": "PMID:201145", "title": "Seitelberger's connatal form of Pelizaeus-Merzbacher Disease. Case report, clinical, pathological and biochemical findings.", "content": "A case of Seitelberger's connatal form of Pelizaeus-Merzbacher disease is reported. He lived to the age of 13 and was able to recognize persons. Both is unusual in this disease. Some of the few myelin sheaths had two different periodicities (150 and 90 A). Intranuclear inclusions similar to Hirano's cytoplasmic eosinophilic rodlets were observed. The findings of connatal form of Pelizaeus-Merzbacher disease are compared with those of dysmyelinating mice (Jimpy and Quacking) and of manipulated myelinating tissue cultures. The possibility is considered, that the alterations in these dysmyelinating human and animal conditions are caused by extraneural circulating factors.", "contents": "Seitelberger's connatal form of Pelizaeus-Merzbacher Disease. Case report, clinical, pathological and biochemical findings. A case of Seitelberger's connatal form of Pelizaeus-Merzbacher disease is reported. He lived to the age of 13 and was able to recognize persons. Both is unusual in this disease. Some of the few myelin sheaths had two different periodicities (150 and 90 A). Intranuclear inclusions similar to Hirano's cytoplasmic eosinophilic rodlets were observed. The findings of connatal form of Pelizaeus-Merzbacher disease are compared with those of dysmyelinating mice (Jimpy and Quacking) and of manipulated myelinating tissue cultures. The possibility is considered, that the alterations in these dysmyelinating human and animal conditions are caused by extraneural circulating factors."}
{"id": "PMID:201146", "title": "Core/targetoid fibres and multiple cytoplasmic bodies in organophosphate neuropathy.", "content": "From correlated histochemical and ultrastructural investigations of biopsy specimens of a rare case with delayed-onset neuropathy due to organophosphate (Dipterex) intoxication, several pathological characteristics were recognized in the muscle fibres. Most striking was concurrence of core/targetoids and multiple cytoplasmic bodies in the same fibres. Foci of markedly reduced or absent oxidative enzyme activity were revealed in 71.6% of type I fibres and in 3.4% of type II fibres. Most of those foci were two-zoned core/targetoids. Cytoplasmic bodies were also revealed selectively in type I fibres contrary to the previous reports. Targets, targetoids, cores and multicores were suggested to be strongly related to each other pathogenetically and to be due to the disturbance of some neurotrophic influences. In the biopsy specimen taken 220 days after exposure to the drug, numerous sarcoplasmic masses were revealed, and they were very likely to represent special forms of regeneration.", "contents": "Core/targetoid fibres and multiple cytoplasmic bodies in organophosphate neuropathy. From correlated histochemical and ultrastructural investigations of biopsy specimens of a rare case with delayed-onset neuropathy due to organophosphate (Dipterex) intoxication, several pathological characteristics were recognized in the muscle fibres. Most striking was concurrence of core/targetoids and multiple cytoplasmic bodies in the same fibres. Foci of markedly reduced or absent oxidative enzyme activity were revealed in 71.6% of type I fibres and in 3.4% of type II fibres. Most of those foci were two-zoned core/targetoids. Cytoplasmic bodies were also revealed selectively in type I fibres contrary to the previous reports. Targets, targetoids, cores and multicores were suggested to be strongly related to each other pathogenetically and to be due to the disturbance of some neurotrophic influences. In the biopsy specimen taken 220 days after exposure to the drug, numerous sarcoplasmic masses were revealed, and they were very likely to represent special forms of regeneration."}
{"id": "PMID:201147", "title": "Pathology of acute ischemic myocardium. Special references to (I) evaluation of morphological methods for detection of early myocardial infarcts, and (II) lipid metabolism in infarcted myocardium.", "content": "Morphological changes of early myocardial infarction within 24 hours after the onset of the acute attack were described together with a review of the literatures. For the practical purpose in detecting very early infarcts, enzymatic histochemistry is the most reliable method. Other methods previously reported such as wavy pattern of the muscle fibers and fuchsinophilia are still controvertial. Lipid metabolism in the infarcted myocardium of dogs was studied both morphologically and biochemically. Up to 3 hours, after the coronary ligation, the tissue lipids accumulated in the necrotic areas with a rise of triglyceride, but later than 6 hours the lipids decreased and were lost from the necrotic tissue, while the surrounding living cells were accumulated with neutral lipids. Serum free fatty acids were elevated in the coronary sinus blood in 6 hours after the ligation. Linolic acids were contained in high proportion in both coronary venous blood after 6 hours, and normal myocardial phospholipid. These results may lead to another possible factor in addition to catecholamine activity to elevate serum FFA in acute myocardial infarction that fatty acids may be released partly from tissue phospholipid and once ever accumulated triglyceride.", "contents": "Pathology of acute ischemic myocardium. Special references to (I) evaluation of morphological methods for detection of early myocardial infarcts, and (II) lipid metabolism in infarcted myocardium. Morphological changes of early myocardial infarction within 24 hours after the onset of the acute attack were described together with a review of the literatures. For the practical purpose in detecting very early infarcts, enzymatic histochemistry is the most reliable method. Other methods previously reported such as wavy pattern of the muscle fibers and fuchsinophilia are still controvertial. Lipid metabolism in the infarcted myocardium of dogs was studied both morphologically and biochemically. Up to 3 hours, after the coronary ligation, the tissue lipids accumulated in the necrotic areas with a rise of triglyceride, but later than 6 hours the lipids decreased and were lost from the necrotic tissue, while the surrounding living cells were accumulated with neutral lipids. Serum free fatty acids were elevated in the coronary sinus blood in 6 hours after the ligation. Linolic acids were contained in high proportion in both coronary venous blood after 6 hours, and normal myocardial phospholipid. These results may lead to another possible factor in addition to catecholamine activity to elevate serum FFA in acute myocardial infarction that fatty acids may be released partly from tissue phospholipid and once ever accumulated triglyceride."}
{"id": "PMID:201148", "title": "Ultrastructural study of thyroid medullary carcinoma.", "content": "This study deals with 11 cases of thyroid medullary carcinoma of which 7 were familial cases including 3 cases of Sipple's syndrome and 4 cases of sporadic cases. There were also 2 cases of Cushing's syndrome. In addition to the previously described English literatures about human medullary carcinoma of the thyroid, the rod-shaped body with cristae and an abundant glycogen particles in the cytoplasm, nuclear inclusion bodies of cytoplasmic invagination and microvilli at the surface membrane of gland formation were found in our cases. The mean and mode diameters of secretory granules of all familial cases with only calcitonin secretion were larger than those of the sporadic cases with ectopic ACTH and beta-MSH in addition to calcitonin secretion. Ultrastructural study on non-cancerous follicles of grossly normal thyroid of two cases of early familial medullary carcinoma disclosed apparently increased C-cells which were not intrathyroidal metastases. It is supposed that the increased C-cells in the thyroid of the familial cases are multicentric C-cell hyperplasia.", "contents": "Ultrastructural study of thyroid medullary carcinoma. This study deals with 11 cases of thyroid medullary carcinoma of which 7 were familial cases including 3 cases of Sipple's syndrome and 4 cases of sporadic cases. There were also 2 cases of Cushing's syndrome. In addition to the previously described English literatures about human medullary carcinoma of the thyroid, the rod-shaped body with cristae and an abundant glycogen particles in the cytoplasm, nuclear inclusion bodies of cytoplasmic invagination and microvilli at the surface membrane of gland formation were found in our cases. The mean and mode diameters of secretory granules of all familial cases with only calcitonin secretion were larger than those of the sporadic cases with ectopic ACTH and beta-MSH in addition to calcitonin secretion. Ultrastructural study on non-cancerous follicles of grossly normal thyroid of two cases of early familial medullary carcinoma disclosed apparently increased C-cells which were not intrathyroidal metastases. It is supposed that the increased C-cells in the thyroid of the familial cases are multicentric C-cell hyperplasia."}
{"id": "PMID:201149", "title": "Histological studies on the effect of ACTH and flavin adenine dinucleotide on the rat adrenal cortex atrophied by hypophysectomy.", "content": "The present study describes the morphological changes in the adrenals of hypophysectomized rats injected 0.03 mg of ACTH and/or 10 mg of FAD intraperitoneally for 5 successive days starting 24 hrs after the operation. The administration of only FAD to intact or hypophysectomized rats showed no morphological change in the adrenal cortex. Simultaneous administration of FAD and ACTH to the hypophysectomized rats is more effective for preventing the atrophy induced than the administration of only ACTH. In these animals, similar morphological observations to those in the control, such as the increased nuclear volume, an increase of clear cells, diminuted numbers of lipid droplets and frequent occurrence of various types of granules, were obtained. FAD seems to be effective, through coexisting with ACTH, for preventing atrophy of the adrenals induced by hypophysectomy.", "contents": "Histological studies on the effect of ACTH and flavin adenine dinucleotide on the rat adrenal cortex atrophied by hypophysectomy. The present study describes the morphological changes in the adrenals of hypophysectomized rats injected 0.03 mg of ACTH and/or 10 mg of FAD intraperitoneally for 5 successive days starting 24 hrs after the operation. The administration of only FAD to intact or hypophysectomized rats showed no morphological change in the adrenal cortex. Simultaneous administration of FAD and ACTH to the hypophysectomized rats is more effective for preventing the atrophy induced than the administration of only ACTH. In these animals, similar morphological observations to those in the control, such as the increased nuclear volume, an increase of clear cells, diminuted numbers of lipid droplets and frequent occurrence of various types of granules, were obtained. FAD seems to be effective, through coexisting with ACTH, for preventing atrophy of the adrenals induced by hypophysectomy."}
{"id": "PMID:201150", "title": "Electron microscopic studies on the effect of ACTH and flavin adenine dinucleotide on adrenocortical atrophy of hypophysectomized rat.", "content": "Electron microscopic observation was made on the outer fasciculata cells in the adrenal cortex of hypophysectomized rats receiving 10 mg of FAD and/or 0.3 mg of ACTH intraperitoneally once a day for 5 consecutive days from 24 hours after hypophysectomy. The simultaneous administration of FAD and ACTH to the hypophysectomized rat was more effective for preventing adrenocortical atrophy induced than the administration of ACTH alone. This effect appeared as clear cells with low electron density. While the characteristics induced by hypophysectomy were the decrease in number of smooth-surfaced endoplasmic reticulum (SER) and mitochondria and also crista of mitochondria being tubular. The clear cells showed a less degree of their characteristic. From this fact, it is considered that the external FAD acts against fasciculata cells in the adrenal cortex of hypophysectomized rats as a coenzyme for flavin enzyme under ACTH and decreases oxidation-reaction in mitochondria and oxidative phosphorilation reaction in SER, being induced by hypophysectomy.", "contents": "Electron microscopic studies on the effect of ACTH and flavin adenine dinucleotide on adrenocortical atrophy of hypophysectomized rat. Electron microscopic observation was made on the outer fasciculata cells in the adrenal cortex of hypophysectomized rats receiving 10 mg of FAD and/or 0.3 mg of ACTH intraperitoneally once a day for 5 consecutive days from 24 hours after hypophysectomy. The simultaneous administration of FAD and ACTH to the hypophysectomized rat was more effective for preventing adrenocortical atrophy induced than the administration of ACTH alone. This effect appeared as clear cells with low electron density. While the characteristics induced by hypophysectomy were the decrease in number of smooth-surfaced endoplasmic reticulum (SER) and mitochondria and also crista of mitochondria being tubular. The clear cells showed a less degree of their characteristic. From this fact, it is considered that the external FAD acts against fasciculata cells in the adrenal cortex of hypophysectomized rats as a coenzyme for flavin enzyme under ACTH and decreases oxidation-reaction in mitochondria and oxidative phosphorilation reaction in SER, being induced by hypophysectomy."}
{"id": "PMID:201151", "title": "Differentiation of human neuroblastoma cells in vitro--morphological changes induced by dibutyrl cyclic AMP.", "content": "Differentiation ability of neuroblastoma cells was studied in vitro, light and electron microscopically using three continuously cultured cell lines (NB-1, GOTO, and YT-nu) of human origin. The cells ordinarily cultured appeared to differentiate along directions of both ganglionic and paraganglionic characterized by cytoplasmic catecholamine granules measuring 150 to 250 treatment with But2cAMP in NB-1 and YT-nu cells, but GOTO cells revealed only one-directed differentiation along ganglionic cell regardless of But2cAMP conditioning. Morphological and functional differentiation of mouse and human neuroblastoma cells in vitro, conversion of rat phenochromocytoma cells into sympathetic neurons in vitro, and ultrastructural differentiation of human neuroblastoma in vivo were discussed. In conclusion, neuroblastoma might be derived from a primitive stem cell of neural crest origin which possesses the pluripotency to be capable of differentiating along the sympathetic, parasympathetic, and other neural crest derivatives under certain conditions.", "contents": "Differentiation of human neuroblastoma cells in vitro--morphological changes induced by dibutyrl cyclic AMP. Differentiation ability of neuroblastoma cells was studied in vitro, light and electron microscopically using three continuously cultured cell lines (NB-1, GOTO, and YT-nu) of human origin. The cells ordinarily cultured appeared to differentiate along directions of both ganglionic and paraganglionic characterized by cytoplasmic catecholamine granules measuring 150 to 250 treatment with But2cAMP in NB-1 and YT-nu cells, but GOTO cells revealed only one-directed differentiation along ganglionic cell regardless of But2cAMP conditioning. Morphological and functional differentiation of mouse and human neuroblastoma cells in vitro, conversion of rat phenochromocytoma cells into sympathetic neurons in vitro, and ultrastructural differentiation of human neuroblastoma in vivo were discussed. In conclusion, neuroblastoma might be derived from a primitive stem cell of neural crest origin which possesses the pluripotency to be capable of differentiating along the sympathetic, parasympathetic, and other neural crest derivatives under certain conditions."}
{"id": "PMID:201153", "title": "Epstein-Barr virus and cytomegalovirus antibodies in infectious mononucleosis.", "content": "A method has been evolved for the demonstration of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection in 83 cases of infectious mononucleosis. Serum samples were tested for EBV IgM, anti-VCA IgG, anti-EBNA, CMV IgM and CMV IgG antibodies. An acute-phase sample (or samples) and a convalescence sample were examined in each case, and in 44 cases an additional samples was examined 5-12 months after the illness. Since the different antibodies showed characteristic differences in both titre and persistence, a reliable serodiagnosis has become possible. Acute EBV infection is characterized by the presence of EBV-VCA IgG and EBV IgG antibodies and the lack of anti-EBNA. The latter becomes demonstrable as late as the 4th to 5th month after infection. Mean age of the patients was 19 years. EBV infection was demonstrated in 65%, CMV infection in 18% of the cases. In 12% double infection seemed to be probable.", "contents": "Epstein-Barr virus and cytomegalovirus antibodies in infectious mononucleosis. A method has been evolved for the demonstration of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection in 83 cases of infectious mononucleosis. Serum samples were tested for EBV IgM, anti-VCA IgG, anti-EBNA, CMV IgM and CMV IgG antibodies. An acute-phase sample (or samples) and a convalescence sample were examined in each case, and in 44 cases an additional samples was examined 5-12 months after the illness. Since the different antibodies showed characteristic differences in both titre and persistence, a reliable serodiagnosis has become possible. Acute EBV infection is characterized by the presence of EBV-VCA IgG and EBV IgG antibodies and the lack of anti-EBNA. The latter becomes demonstrable as late as the 4th to 5th month after infection. Mean age of the patients was 19 years. EBV infection was demonstrated in 65%, CMV infection in 18% of the cases. In 12% double infection seemed to be probable."}
{"id": "PMID:201154", "title": "Cytomegalovirus-induced membrane antigens in productively infected cells.", "content": "Adsorbed but not penetrated virus can be removed from the CMV-infected cell membrane by digestion with cystine-activated papain. Membrane antigens appear on 80-90% of the infected cells 14-20 hr after infection as a result of de novo protein synthesis. Antigen synthesis can be blocked with inhibitors of protein synthesis, but not with DNA inhibitors. In the early stage of infection, pooled human convalescent serum reacted well with the membrane antigen, whereas pooled antiserum of rabbits immunized with CMV virion suspension gave a positive reaction with a small proportion of the cells. After the 48th hr, both the human and the rabbit serum pool reacted with the membrane of the infected cells. Absorption with cell cultured for 24 hr after CMV infection reduced the neutralization titres of the antisera only slightly but the titre reduction was considerable when absorption was performed with cells cultured for more than 48 hr after infection. It is concluded that on the membrane of cells productively infected by CMV at least two membrane antigens are present, one coded for by the DNA of the parent virus and another which is the product of the DNA of the virus progeny. The two antigens can be differentiated serologically.", "contents": "Cytomegalovirus-induced membrane antigens in productively infected cells. Adsorbed but not penetrated virus can be removed from the CMV-infected cell membrane by digestion with cystine-activated papain. Membrane antigens appear on 80-90% of the infected cells 14-20 hr after infection as a result of de novo protein synthesis. Antigen synthesis can be blocked with inhibitors of protein synthesis, but not with DNA inhibitors. In the early stage of infection, pooled human convalescent serum reacted well with the membrane antigen, whereas pooled antiserum of rabbits immunized with CMV virion suspension gave a positive reaction with a small proportion of the cells. After the 48th hr, both the human and the rabbit serum pool reacted with the membrane of the infected cells. Absorption with cell cultured for 24 hr after CMV infection reduced the neutralization titres of the antisera only slightly but the titre reduction was considerable when absorption was performed with cells cultured for more than 48 hr after infection. It is concluded that on the membrane of cells productively infected by CMV at least two membrane antigens are present, one coded for by the DNA of the parent virus and another which is the product of the DNA of the virus progeny. The two antigens can be differentiated serologically."}
{"id": "PMID:201160", "title": "L-dopa-induced hypotension: depression of spinal sympathetic neurons by release of 5-hydroxytryptamine.", "content": "In studies designed to determine the respective functional roles of two bulbospinal monoaminergic pathways to sympathetic preganglionic neurons, both L-dopa and precursors of 5-HT depressed transmission through excitatory spinal reflex and bulbospinal sympathetic pathways. Transmission through spinal reflex pathways was secondarily enhanced after L-dopa. Pharmacological tests indicated mediation of these affects by monoamines. After antagonism or depletion of central 5-HT, L-dopa only enhanced transmission through both pathways. The results indicate that hypotension and other sympathoinhibitory effects of L-dopa are produced at the spinal level by release of 5-HT from terminals of bulbospinal 5-HT pathways that are inhibitory to sympathetic preganglionic neurons. The excitatory effects of L-dopa are apparently mediated by release of catecholamines from bulbospinal noradrenergic pathways that are excitatory.", "contents": "L-dopa-induced hypotension: depression of spinal sympathetic neurons by release of 5-hydroxytryptamine. In studies designed to determine the respective functional roles of two bulbospinal monoaminergic pathways to sympathetic preganglionic neurons, both L-dopa and precursors of 5-HT depressed transmission through excitatory spinal reflex and bulbospinal sympathetic pathways. Transmission through spinal reflex pathways was secondarily enhanced after L-dopa. Pharmacological tests indicated mediation of these affects by monoamines. After antagonism or depletion of central 5-HT, L-dopa only enhanced transmission through both pathways. The results indicate that hypotension and other sympathoinhibitory effects of L-dopa are produced at the spinal level by release of 5-HT from terminals of bulbospinal 5-HT pathways that are inhibitory to sympathetic preganglionic neurons. The excitatory effects of L-dopa are apparently mediated by release of catecholamines from bulbospinal noradrenergic pathways that are excitatory."}
{"id": "PMID:201163", "title": "Bradykinin action in the rat duodenum through the cyclic AMP system.", "content": "Activators of the adenylate cyclase or inhibitors of the cAMP-phosphodiesterase, respectively, potentiate the bradykinin-induced relaxation of the rat duodenum, whereas imidazole as a stimulator of the cAMP-phosphodiesterase reduces the relaxation. The experiments indicate a linkage between the adenylate cyclase system with the biological action of bradykinin on the rat duodenum. In contrast, no similar effect has been observed on the rat uterus.", "contents": "Bradykinin action in the rat duodenum through the cyclic AMP system. Activators of the adenylate cyclase or inhibitors of the cAMP-phosphodiesterase, respectively, potentiate the bradykinin-induced relaxation of the rat duodenum, whereas imidazole as a stimulator of the cAMP-phosphodiesterase reduces the relaxation. The experiments indicate a linkage between the adenylate cyclase system with the biological action of bradykinin on the rat duodenum. In contrast, no similar effect has been observed on the rat uterus."}
{"id": "PMID:201167", "title": "Familial hypo-beta-lipoproteinemia: a family detected by cord blood tests.", "content": "A family with low-density lipoprotein (LDL) deficiency was detected during the course of screening cord blood samples. The initial diagnosis in the proband was based on the cord blood LDL cholesterol and lipoprotein electrophoretic pattern, and was confirmed by repeated studies at the age of 8 months. The infant had none of the clinical abnormalities previously ascribed to the condition. Further investigation did not disclose any other significant biochemical or histological abnormalities. Hypo-beta-lipoproteinemia was found to exist in the proband's mother and only sibling. Hence the diagnosis of familial hypo-beta-lipoproteinemia is possible by unselected cord blood LDL cholesterol measurement and lipoprotein electrophoresis in conjunction with kindred studies.", "contents": "Familial hypo-beta-lipoproteinemia: a family detected by cord blood tests. A family with low-density lipoprotein (LDL) deficiency was detected during the course of screening cord blood samples. The initial diagnosis in the proband was based on the cord blood LDL cholesterol and lipoprotein electrophoretic pattern, and was confirmed by repeated studies at the age of 8 months. The infant had none of the clinical abnormalities previously ascribed to the condition. Further investigation did not disclose any other significant biochemical or histological abnormalities. Hypo-beta-lipoproteinemia was found to exist in the proband's mother and only sibling. Hence the diagnosis of familial hypo-beta-lipoproteinemia is possible by unselected cord blood LDL cholesterol measurement and lipoprotein electrophoresis in conjunction with kindred studies."}
{"id": "PMID:201170", "title": "Viral hepatitis: enzyme assays and serologic procedures in the study of an epidemic.", "content": "An epidemic of viral hepatitis beginning in late 1975 in a residence for multiply handicapped children, recognized very early in its course, was investigated prospectively to permit comparison of enzymatic and serologic tests. Thirty-three residents of the institution and 46 full- and part-time employees were studied by the immune adherence hemagglutination procedure for antibody (anti-HAV) to hepatitis A virus (HAV). Of these, 31 residents and 37 staff members were susceptible at the beginning of the epidemic. Nineteen and six, respectively, had anti-HAV seroconversion indicating HAV infection. Thus, 12 children (39%) and 31 staff members (81%) of presumed susceptibles did not have serologic evidence of infection. The subclinical/clinical ratio for the children was 1.1:1; for personnel, it was 1:1. Serum alanine aminotransferase (ALT) levels compatible with viral hepatitis occurred in 21 persons (84%) who had anti-HAV seroconversion; conversely, there were 10 persons who had ALT abnormality without detectable anti-HAV in late specimens among the total of 68 susceptibles. There was no evidence the latter could be attributed to hepatitis B virus infection; therefore, they may represent the endemic occurrence of non-A, non-B agent(s).", "contents": "Viral hepatitis: enzyme assays and serologic procedures in the study of an epidemic. An epidemic of viral hepatitis beginning in late 1975 in a residence for multiply handicapped children, recognized very early in its course, was investigated prospectively to permit comparison of enzymatic and serologic tests. Thirty-three residents of the institution and 46 full- and part-time employees were studied by the immune adherence hemagglutination procedure for antibody (anti-HAV) to hepatitis A virus (HAV). Of these, 31 residents and 37 staff members were susceptible at the beginning of the epidemic. Nineteen and six, respectively, had anti-HAV seroconversion indicating HAV infection. Thus, 12 children (39%) and 31 staff members (81%) of presumed susceptibles did not have serologic evidence of infection. The subclinical/clinical ratio for the children was 1.1:1; for personnel, it was 1:1. Serum alanine aminotransferase (ALT) levels compatible with viral hepatitis occurred in 21 persons (84%) who had anti-HAV seroconversion; conversely, there were 10 persons who had ALT abnormality without detectable anti-HAV in late specimens among the total of 68 susceptibles. There was no evidence the latter could be attributed to hepatitis B virus infection; therefore, they may represent the endemic occurrence of non-A, non-B agent(s)."}
{"id": "PMID:201171", "title": "Corticosteroid-responsive skeletal muscle disease associated with partial carnitine deficiency: studies of liver and metabolic alterations.", "content": "A patient with progressive skeletal muscle weakness had lipid-containing vacuoles in type I muscle fibers and partial carnitine deficiency of skeletal muscle. Results of certain liver function tests were abnormal, marked morphologic abnormalities of liver were detected, and a reduced cyclic adenosine 3',5'-monophosphate response to glucagon was present. After the oral administration of prednisone the patient exhibited gradual but striking clinical improvement, skeletal muscle fiber vacuoles could no longer be demonstrated, and the glucagon-provoked cyclic AMP response reverted to normal, but liver abnormalities persisted. At the same time utilization by skeletal muscle of long-chain fatty acids, pyruvate and beta-hydroxybutyrate was depressed. It is possible that the involvement of skeletal muscles was due to an inability of carnitine to attach to or to penetrate the sarcolemmal membrane. Some of the derangement, perhaps related to liver malfunction, was apparently corrected by the oral administration of prednisone although skeletal muscle metabolism remained impaired.", "contents": "Corticosteroid-responsive skeletal muscle disease associated with partial carnitine deficiency: studies of liver and metabolic alterations. A patient with progressive skeletal muscle weakness had lipid-containing vacuoles in type I muscle fibers and partial carnitine deficiency of skeletal muscle. Results of certain liver function tests were abnormal, marked morphologic abnormalities of liver were detected, and a reduced cyclic adenosine 3',5'-monophosphate response to glucagon was present. After the oral administration of prednisone the patient exhibited gradual but striking clinical improvement, skeletal muscle fiber vacuoles could no longer be demonstrated, and the glucagon-provoked cyclic AMP response reverted to normal, but liver abnormalities persisted. At the same time utilization by skeletal muscle of long-chain fatty acids, pyruvate and beta-hydroxybutyrate was depressed. It is possible that the involvement of skeletal muscles was due to an inability of carnitine to attach to or to penetrate the sarcolemmal membrane. Some of the derangement, perhaps related to liver malfunction, was apparently corrected by the oral administration of prednisone although skeletal muscle metabolism remained impaired."}
{"id": "PMID:201173", "title": "Growth characteristics of populations of Tibetan origin in Nepal.", "content": "Previous growth studies of highland-dwelling populations in the ecologically diverse areas of Peru and Ethiopia have yielded highly varied results: the retarded growth of the Peruvian sample was attributed to the effects of hypoxia, while the increased height and weight of the highland Ethiopian sample could be traced to better health conditions in the highland village than in the lowland village studied. In an attempt to provide a basis for evaluating studies of growth at high altitude, the present study compared Sherpa children living in the Everest region of Nepal with Tibetan children living in Kathmandu. It was found that: (1) the growth of Sherpa and Tibetan children is considerably retarded compared to other high altitude populations; (2) despite conditions favorable for optimum growth among the Tibetans, their growth resembled that of the Sherpas and (3) increased chest circumference, which seems to reflect a developmental acclimatization to hypoxia among Peruvian high-altitude natives, was not seen among the Sherpas.", "contents": "Growth characteristics of populations of Tibetan origin in Nepal. Previous growth studies of highland-dwelling populations in the ecologically diverse areas of Peru and Ethiopia have yielded highly varied results: the retarded growth of the Peruvian sample was attributed to the effects of hypoxia, while the increased height and weight of the highland Ethiopian sample could be traced to better health conditions in the highland village than in the lowland village studied. In an attempt to provide a basis for evaluating studies of growth at high altitude, the present study compared Sherpa children living in the Everest region of Nepal with Tibetan children living in Kathmandu. It was found that: (1) the growth of Sherpa and Tibetan children is considerably retarded compared to other high altitude populations; (2) despite conditions favorable for optimum growth among the Tibetans, their growth resembled that of the Sherpas and (3) increased chest circumference, which seems to reflect a developmental acclimatization to hypoxia among Peruvian high-altitude natives, was not seen among the Sherpas."}
{"id": "PMID:201174", "title": "The application of EEG sleep for the differential diagnosis of affective disorders.", "content": "On the basis of two EEG sleep criteria, REM latency and REM activity, the authors achieved 81% accuracy in distinguishing between 47 patients with primary depression and 48 patients with secondary depression using discriminant analysis. Sleep efficiency, the percentage of delta sleep, and the percentage of REM sleep discriminated between psychotic and nonpsychotic subgroups in the group with primary depression with 75% accuracy. REM activity and intermittent nocturnal awakening accurately discriminated two subtypes of patients with secondary depression at a level of 81%. These results suggest  that EEG sleep measurements can yield significant data to aid in differential diagnosis in psychiatry.", "contents": "The application of EEG sleep for the differential diagnosis of affective disorders. On the basis of two EEG sleep criteria, REM latency and REM activity, the authors achieved 81% accuracy in distinguishing between 47 patients with primary depression and 48 patients with secondary depression using discriminant analysis. Sleep efficiency, the percentage of delta sleep, and the percentage of REM sleep discriminated between psychotic and nonpsychotic subgroups in the group with primary depression with 75% accuracy. REM activity and intermittent nocturnal awakening accurately discriminated two subtypes of patients with secondary depression at a level of 81%. These results suggest  that EEG sleep measurements can yield significant data to aid in differential diagnosis in psychiatry."}
{"id": "PMID:201184", "title": "Comparison of intestinal (Illinois strain) and cell culture-adapted (M-HP strain) viral populations of transmissible gastroenteritis of swine.", "content": "Intestinal and cell culture-adapted viral populations of transmissible gastroenteritis (TGE) of swine were compared by means of sucrose gradient centrifugation, immunnofluorescence, electron microscopy, immune electron microscopy, statistical analysis of the number of plaque-forming units, and ultraviolet sensitivity. Results indicated that the size range and general coronavirus morphologic characteristics were shared by both viral populations. Marked morphologic variations existed among particles from both populations. Unlike the cell culture-adapted virus, the Illinois virus of intestinal origin was infractions representing 2 bands of infectivity which were isolated by the sucrose gradient centrifugation method. The intestinal and cell culture-adapted TGE viruses were similar in antigenicity and in sensitivity to ultraviolet irradiation. There was no indication of a 2nd virus in addition to the coronavirus described as the cause of TGE.", "contents": "Comparison of intestinal (Illinois strain) and cell culture-adapted (M-HP strain) viral populations of transmissible gastroenteritis of swine. Intestinal and cell culture-adapted viral populations of transmissible gastroenteritis (TGE) of swine were compared by means of sucrose gradient centrifugation, immunnofluorescence, electron microscopy, immune electron microscopy, statistical analysis of the number of plaque-forming units, and ultraviolet sensitivity. Results indicated that the size range and general coronavirus morphologic characteristics were shared by both viral populations. Marked morphologic variations existed among particles from both populations. Unlike the cell culture-adapted virus, the Illinois virus of intestinal origin was infractions representing 2 bands of infectivity which were isolated by the sucrose gradient centrifugation method. The intestinal and cell culture-adapted TGE viruses were similar in antigenicity and in sensitivity to ultraviolet irradiation. There was no indication of a 2nd virus in addition to the coronavirus described as the cause of TGE."}
{"id": "PMID:201185", "title": "Clinical and immunologic responses of cattle to infectious bovine rhinotracheitis virus after infection by viral aerosol or intramuscular inoculation.", "content": "Aerosol or intramuscular exposure to infectious bovine rhinotracheitis virus elicited generally comparable levels of serum antibody in cattle, but not measurable nasal secretion antibody. Aerosol-exposed cattle developed signs of mild clinical disease, fever, and leukopenia and shed virus from their nasal passages. Cattle exposed by intra-muscular inoculation developed a brief febrile response and leukopenia but did not shed virus. After an aerosol challenge exposure, cattle in each group developed detectable nasal secretion antibodies, but no clinical signs of disease.", "contents": "Clinical and immunologic responses of cattle to infectious bovine rhinotracheitis virus after infection by viral aerosol or intramuscular inoculation. Aerosol or intramuscular exposure to infectious bovine rhinotracheitis virus elicited generally comparable levels of serum antibody in cattle, but not measurable nasal secretion antibody. Aerosol-exposed cattle developed signs of mild clinical disease, fever, and leukopenia and shed virus from their nasal passages. Cattle exposed by intra-muscular inoculation developed a brief febrile response and leukopenia but did not shed virus. After an aerosol challenge exposure, cattle in each group developed detectable nasal secretion antibodies, but no clinical signs of disease."}
{"id": "PMID:201186", "title": "Vaccination of cattle and sheep with a combined Clostridium perfringens types C and D toxoid.", "content": "Cattle and sheep (30 each) were vaccinated with a combined Clostridium perfringens type C and C perfringens type D toxoid. Vaccination and blood sample collections were made every 2 weeks over a period of 8 weeks. Increases in antitoxin titers occurred after the 2nd administration of the 2.0-ml combined product. Highest titers were recorded when the 2nd vaccinal dose was given 2 weeks after the first. This confirms reports that response to clostridial antigens is greater when the 2nd immunizing dose is delayed 2 to 6 weeks after the initial dose.", "contents": "Vaccination of cattle and sheep with a combined Clostridium perfringens types C and D toxoid. Cattle and sheep (30 each) were vaccinated with a combined Clostridium perfringens type C and C perfringens type D toxoid. Vaccination and blood sample collections were made every 2 weeks over a period of 8 weeks. Increases in antitoxin titers occurred after the 2nd administration of the 2.0-ml combined product. Highest titers were recorded when the 2nd vaccinal dose was given 2 weeks after the first. This confirms reports that response to clostridial antigens is greater when the 2nd immunizing dose is delayed 2 to 6 weeks after the initial dose."}
{"id": "PMID:201188", "title": "Platelet affinity for burro aorta collagen.", "content": "Despite ingenious concepts, there are no unequivocal clues as to what, when, and how some undefined biochemical factor(s) or constituent(s) that localizes in the arterial wall can precipitate a thromboatheromatous lesion or arterial disease. The present study focused on the extraction, partial purification, and characterization of a collagen-active platelet stimulator from the aortas of aged burros. The aggregator moiety in the aorta extracts invariably had a higher affinity for platelets in citrated platelet-rich plasma of human beings than for platelets of homologous burros. The platelet-aggregating factor(s) in the aorta extract was retained by incubation with alpha-chymotrypsin. Platelet-aggregating activity was rapidldy abolished after incubation with collagenase, as determined by plateletaggregometry tests. Evidence based on light microscope and polysaccharide histochemical reactions indicates a probability that the intracellular amorphous matrix (PAS-positive) and filamentous components (PTAH-positive) expelled from smooth muscle cells disrupted during homogenization of the aorta may be a principle source of a precursor collagen species which is a potent inducer of platelet aggregation.", "contents": "Platelet affinity for burro aorta collagen. Despite ingenious concepts, there are no unequivocal clues as to what, when, and how some undefined biochemical factor(s) or constituent(s) that localizes in the arterial wall can precipitate a thromboatheromatous lesion or arterial disease. The present study focused on the extraction, partial purification, and characterization of a collagen-active platelet stimulator from the aortas of aged burros. The aggregator moiety in the aorta extracts invariably had a higher affinity for platelets in citrated platelet-rich plasma of human beings than for platelets of homologous burros. The platelet-aggregating factor(s) in the aorta extract was retained by incubation with alpha-chymotrypsin. Platelet-aggregating activity was rapidldy abolished after incubation with collagenase, as determined by plateletaggregometry tests. Evidence based on light microscope and polysaccharide histochemical reactions indicates a probability that the intracellular amorphous matrix (PAS-positive) and filamentous components (PTAH-positive) expelled from smooth muscle cells disrupted during homogenization of the aorta may be a principle source of a precursor collagen species which is a potent inducer of platelet aggregation."}
{"id": "PMID:201189", "title": "Detection of inapparent Aleutian disease virus infection in mink.", "content": "The normal serum gamma-globulin centration of mink from the Ontario Veterinary College field station was 13.2 +/- 2.6% of total serum proteins. Mink serum gamma-globulin concentrations above 21%, which represented 3 standard deviations above the normal mean, were considered to be hypergammaglobulinemic. About 39% of pastel mink infected naturally with Aleutin disease virus (ADV) exhibited an inapparent or nonprogressive infection. These nonprogressivley infected mink had serum gamma-globulin values below 21% andhad antibody titers less than 256 if tested by the couterimmunoelectrophoresis technique. Mink maintained inapparent infection for at least 10 months after infection with ADV. Neither gross nor histopathologic changes were present in the mink with inapparent ADV infection. The virus persisted in blood, mesenteric lymph nodes, kidney, liver, and spleen of mink with non-progressive infection, although the amount of virus present probably was small.", "contents": "Detection of inapparent Aleutian disease virus infection in mink. The normal serum gamma-globulin centration of mink from the Ontario Veterinary College field station was 13.2 +/- 2.6% of total serum proteins. Mink serum gamma-globulin concentrations above 21%, which represented 3 standard deviations above the normal mean, were considered to be hypergammaglobulinemic. About 39% of pastel mink infected naturally with Aleutin disease virus (ADV) exhibited an inapparent or nonprogressive infection. These nonprogressivley infected mink had serum gamma-globulin values below 21% andhad antibody titers less than 256 if tested by the couterimmunoelectrophoresis technique. Mink maintained inapparent infection for at least 10 months after infection with ADV. Neither gross nor histopathologic changes were present in the mink with inapparent ADV infection. The virus persisted in blood, mesenteric lymph nodes, kidney, liver, and spleen of mink with non-progressive infection, although the amount of virus present probably was small."}
{"id": "PMID:201190", "title": "Characterization of herpesviruses isolated from lactating dairy cows with mammary pustular dermatitis.", "content": "Herpesviruses serologically indistinguishable from the DN599 strain of bovine herpesvirus were isolated from 2 separate enzootics of mammary pustular dermatitis in lactating Holstein-Friesian cows.", "contents": "Characterization of herpesviruses isolated from lactating dairy cows with mammary pustular dermatitis. Herpesviruses serologically indistinguishable from the DN599 strain of bovine herpesvirus were isolated from 2 separate enzootics of mammary pustular dermatitis in lactating Holstein-Friesian cows."}
{"id": "PMID:201191", "title": "Plasma adrenocorticotropin levels in normal dogs.", "content": "Plasma concentrations of adrenocorticotropin (ACTH; corticotropin) were measured in 31 normal dogs (house pets) at rest. The mean concentration was 45.77 pg/ml of blood, with individual values ranging from 17 to 98 pg/ml of blood. The measurement of this hormone secreted by the anterior lobe of the pituitary gland (adenohypophysis) may aid in the diagnosis of spontaneous canine adrenal cortical disorders, both primary and secondary.", "contents": "Plasma adrenocorticotropin levels in normal dogs. Plasma concentrations of adrenocorticotropin (ACTH; corticotropin) were measured in 31 normal dogs (house pets) at rest. The mean concentration was 45.77 pg/ml of blood, with individual values ranging from 17 to 98 pg/ml of blood. The measurement of this hormone secreted by the anterior lobe of the pituitary gland (adenohypophysis) may aid in the diagnosis of spontaneous canine adrenal cortical disorders, both primary and secondary."}
{"id": "PMID:201193", "title": "Bluetongue in cattle: effects of vector-transmitted bluetongue virus on calves previously infected in utero.", "content": "Three of 7 principal calves, after a challenge of immunity exposure by bites of bluetongue (BT) virus-infected Culicoides variipennis, became latently infected with BT virus. These calves were born to heifers infected with the homologous virus by bites of C variipennis at 60 or 120 days' gestation. Latent BT virus infection was detected by isolation of BT virus from washed erythrocyte samples obtained from the calves at 57, 100 to 102, 200 to 202, 300 to 302, and 400 to 402 days after challenge of immunity and from 1 of the calves over 5 years after challenge of immunity. The 3 latently infected calves were healthy; 2 were immunologically competent and 1 was immunologically incompetent to develop detectable BT virus antibodies in their blood. Bluetongue virus infection was detected (by viral isolation) in 2 other principal calves during the challenge of immunity, but they were not considered latently infected. The latter 2 calves were immunologically incompetent to develop detectable BT virus antibodies.", "contents": "Bluetongue in cattle: effects of vector-transmitted bluetongue virus on calves previously infected in utero. Three of 7 principal calves, after a challenge of immunity exposure by bites of bluetongue (BT) virus-infected Culicoides variipennis, became latently infected with BT virus. These calves were born to heifers infected with the homologous virus by bites of C variipennis at 60 or 120 days' gestation. Latent BT virus infection was detected by isolation of BT virus from washed erythrocyte samples obtained from the calves at 57, 100 to 102, 200 to 202, 300 to 302, and 400 to 402 days after challenge of immunity and from 1 of the calves over 5 years after challenge of immunity. The 3 latently infected calves were healthy; 2 were immunologically competent and 1 was immunologically incompetent to develop detectable BT virus antibodies in their blood. Bluetongue virus infection was detected (by viral isolation) in 2 other principal calves during the challenge of immunity, but they were not considered latently infected. The latter 2 calves were immunologically incompetent to develop detectable BT virus antibodies."}
{"id": "PMID:201194", "title": "Bluetongue in cattle: repeated exposure of two immunologically tolerant calves to bluetongue virus by vector bites.", "content": "A heifer and steer that were immunologically tolerant to bluetongue (BT) virus became immunologically competent after repeated exposures by bites of BT virus-infected Culicoides variipennis. Immunologic tolerance ended in the heifer at 25 months of age, after the 2nd exposure to the virus, and in the steer at 22 months, after the 4th exposure. High hemic concentrations of BT virus were detected in both animals after they became immunologically competent, but neither developed an overt BT clinical response. The steer died suddenly and extensive pathologic changes were observed at necropsy.", "contents": "Bluetongue in cattle: repeated exposure of two immunologically tolerant calves to bluetongue virus by vector bites. A heifer and steer that were immunologically tolerant to bluetongue (BT) virus became immunologically competent after repeated exposures by bites of BT virus-infected Culicoides variipennis. Immunologic tolerance ended in the heifer at 25 months of age, after the 2nd exposure to the virus, and in the steer at 22 months, after the 4th exposure. High hemic concentrations of BT virus were detected in both animals after they became immunologically competent, but neither developed an overt BT clinical response. The steer died suddenly and extensive pathologic changes were observed at necropsy."}
{"id": "PMID:201195", "title": "Susceptibility of bovine macrophage and tracheal-ring cultures to bovine viruses.", "content": "Cultures of macrophages initiated from peripheral blood monocytes and organ cultures of tracheal rings were tested for their susceptibility to bovine viruses. With several notable exceptions, viruses cytopathogenic for bovine embryonic lung cultures were cytopathogenic for macrophages. Although cowpox virus replicated in macrophages, pseudocowpox did not, and although pseudorabies virus replicated within macrophages, infectious bovine rhinotracheitis and DN-599 herpesviruses did not. Bluetongue virus established an interesting relationship with macrophages. Whereas bluetongue virus was initially cytopathogenic for macrophages, it lost its cytopathogenicity on repeated passage, although it was capable of continued replication in macrophages. When subsequently passaged onto bovine embryonic lung cultures, it regained its cytopathogenicity. Parainfluenza-3, bovine viral diarrhea, and infectious bovine rhinotracheitis viruses readily destroyed ciliary activity in tracheal-ring cultures, as contrasted with the inability of bovine respiratory syncytial virus to destroy ciliary activity, even though bovine respiratory syncytial virus was able to replicate within ciliated epithelial cells of tracheal rings.", "contents": "Susceptibility of bovine macrophage and tracheal-ring cultures to bovine viruses. Cultures of macrophages initiated from peripheral blood monocytes and organ cultures of tracheal rings were tested for their susceptibility to bovine viruses. With several notable exceptions, viruses cytopathogenic for bovine embryonic lung cultures were cytopathogenic for macrophages. Although cowpox virus replicated in macrophages, pseudocowpox did not, and although pseudorabies virus replicated within macrophages, infectious bovine rhinotracheitis and DN-599 herpesviruses did not. Bluetongue virus established an interesting relationship with macrophages. Whereas bluetongue virus was initially cytopathogenic for macrophages, it lost its cytopathogenicity on repeated passage, although it was capable of continued replication in macrophages. When subsequently passaged onto bovine embryonic lung cultures, it regained its cytopathogenicity. Parainfluenza-3, bovine viral diarrhea, and infectious bovine rhinotracheitis viruses readily destroyed ciliary activity in tracheal-ring cultures, as contrasted with the inability of bovine respiratory syncytial virus to destroy ciliary activity, even though bovine respiratory syncytial virus was able to replicate within ciliated epithelial cells of tracheal rings."}
{"id": "PMID:201196", "title": "Investigation of causative agents of bovine respiratory tract disease in a beef cow-calf herd with an early weaning program.", "content": "Serum samples were collected from early weaned fall calves shortly after the onset of respiratory tract disease. Antibody titers to infectious bovine rhinotracheitis (IBR) virus, parainfluenza type 3 (PI-3) virus, bovine viral diarrhea (BVD) virus, bovine adenovirus type 3 (BAV-3), and bovine respiratory syncytial virus (BRSV) were determined on paired (acute and convalescent) serums. Seroconversion rate (a fourfold or greater rise in antibody titer) for IBR virus was 4.3%, PI-3 virus--16.3%, BVD virus--9.6%, and BAV-3--2.2%. Seroconversion for BRSV was 45.4%. An increased rate of seroconversion for IBR, PI-3, and BVD viruses and BAV-3 was observed in the presence of BRSV seroconversion. These results suggest that BRSV may facilitate infection by other viruses. Results of virus isolation procedures from these calves were negative.", "contents": "Investigation of causative agents of bovine respiratory tract disease in a beef cow-calf herd with an early weaning program. Serum samples were collected from early weaned fall calves shortly after the onset of respiratory tract disease. Antibody titers to infectious bovine rhinotracheitis (IBR) virus, parainfluenza type 3 (PI-3) virus, bovine viral diarrhea (BVD) virus, bovine adenovirus type 3 (BAV-3), and bovine respiratory syncytial virus (BRSV) were determined on paired (acute and convalescent) serums. Seroconversion rate (a fourfold or greater rise in antibody titer) for IBR virus was 4.3%, PI-3 virus--16.3%, BVD virus--9.6%, and BAV-3--2.2%. Seroconversion for BRSV was 45.4%. An increased rate of seroconversion for IBR, PI-3, and BVD viruses and BAV-3 was observed in the presence of BRSV seroconversion. These results suggest that BRSV may facilitate infection by other viruses. Results of virus isolation procedures from these calves were negative."}
{"id": "PMID:201197", "title": "Occurrence of cross reactions to foot-and-mouth disease virus in normal swine sera.", "content": "Sera from 101 swine never exposed to foot-and-mouth disease virus were tested by the plaque-reduction neutralization (PRN) and radial immunodiffusion techniques for cross-reactions to 5 types of foot-and-mouth disease viruses. Depending on the group of sera and the virus used, the percentage of sera cross-reacting at low levels varied from 0 to 50% with the PRN technique and 0 to 20% with the radial immunodiffusion technique. 5erum-neutralization tests in mice support the finding of neutralizing antibody by the PRN technique. Ultracentrifugation and 2-mercaptoethanol studies indicate that the cross-reactions are the result of immunoglobulin M or similar macroglobulins.", "contents": "Occurrence of cross reactions to foot-and-mouth disease virus in normal swine sera. Sera from 101 swine never exposed to foot-and-mouth disease virus were tested by the plaque-reduction neutralization (PRN) and radial immunodiffusion techniques for cross-reactions to 5 types of foot-and-mouth disease viruses. Depending on the group of sera and the virus used, the percentage of sera cross-reacting at low levels varied from 0 to 50% with the PRN technique and 0 to 20% with the radial immunodiffusion technique. 5erum-neutralization tests in mice support the finding of neutralizing antibody by the PRN technique. Ultracentrifugation and 2-mercaptoethanol studies indicate that the cross-reactions are the result of immunoglobulin M or similar macroglobulins."}
{"id": "PMID:201198", "title": "Cell culture propagation of porcine rotavirus (reovirus-like agent).", "content": "Two isolates of porcine rotavirus (reovirus-like agent) were isolated and passaged in primary procine kidney cell cultures. Viral infectivity for cells was monitored by immunofluorescence because viral cytopathic effect was moderate. Successful passage of virus in cell culture required that viral suspensions obtained from infected cell cultures be treated with pancreatin prior to inoculation onto cell monolayers. Porcine rotavirus passage in cell culture also was accomplished, using trypsin treatments in lieu of pancreatin treatments. Porcine rotavirus passaged 10 times in cell culture infected gnotobiotic pigs and caused diarrhea. Gnotobiotic pigs that recovered from this infection were resistant to challenge exposure with porcine rotavirus but were susceptible to challenge exposure with transmissible gastroenteritis virus. As determined by immunofluorescent cross reactions, porcine rotavirus was found to be antigenically related to the human and bovine rotaviruses but not to reovirus type 3 or to transmissible gastroenteritis virus.", "contents": "Cell culture propagation of porcine rotavirus (reovirus-like agent). Two isolates of porcine rotavirus (reovirus-like agent) were isolated and passaged in primary procine kidney cell cultures. Viral infectivity for cells was monitored by immunofluorescence because viral cytopathic effect was moderate. Successful passage of virus in cell culture required that viral suspensions obtained from infected cell cultures be treated with pancreatin prior to inoculation onto cell monolayers. Porcine rotavirus passage in cell culture also was accomplished, using trypsin treatments in lieu of pancreatin treatments. Porcine rotavirus passaged 10 times in cell culture infected gnotobiotic pigs and caused diarrhea. Gnotobiotic pigs that recovered from this infection were resistant to challenge exposure with porcine rotavirus but were susceptible to challenge exposure with transmissible gastroenteritis virus. As determined by immunofluorescent cross reactions, porcine rotavirus was found to be antigenically related to the human and bovine rotaviruses but not to reovirus type 3 or to transmissible gastroenteritis virus."}
{"id": "PMID:201201", "title": "Adenosine 3',5'-monophosphate in plasma, urine, and native and isoproterenol-stimulated leukocytes of dogs.", "content": "Adenosine 3',5'-monophosphate (cAMP) was determined by means of a commercial kit in urine and plasma from 40 hospitalized dogs and in native and isoproternol-stimulated leukocytes from 30 of these animals. Mean urine and plasma concentrations were 6.1 micron and 14 nM, with 95% tolerance limits (\"normal values\") ranging from 0.0 to 12 micron and 0.21 to 27 nM, respectively. The plasma concentration was approximately half the value previously reported for experimental dogs. The median cAMP content in native leukocytes was 5.9 pmol/10(7) cells. The mean response to isoproterenol was 0.85 pmol/10(7) cells, much less than in human leukocytes. The response was statistically significant (P less than 0.01), but was so small that it is unlikely to be measurably affected in atopic dogs.", "contents": "Adenosine 3',5'-monophosphate in plasma, urine, and native and isoproterenol-stimulated leukocytes of dogs. Adenosine 3',5'-monophosphate (cAMP) was determined by means of a commercial kit in urine and plasma from 40 hospitalized dogs and in native and isoproternol-stimulated leukocytes from 30 of these animals. Mean urine and plasma concentrations were 6.1 micron and 14 nM, with 95% tolerance limits (\"normal values\") ranging from 0.0 to 12 micron and 0.21 to 27 nM, respectively. The plasma concentration was approximately half the value previously reported for experimental dogs. The median cAMP content in native leukocytes was 5.9 pmol/10(7) cells. The mean response to isoproterenol was 0.85 pmol/10(7) cells, much less than in human leukocytes. The response was statistically significant (P less than 0.01), but was so small that it is unlikely to be measurably affected in atopic dogs."}
{"id": "PMID:201202", "title": "Bovine leukemia virus-associated antigens in lymphocyte cultures.", "content": "Short-term lymphocyte cultures from bovine leukemia virus (BLV)-infected cattle were tested for BLV-associated antigens at various times after incubation. Several immunologic methods were used, including fluorescent antibody tests, immunodiffusion, and radial immunodiffusion. Antigens were not detected in uncultured lymphocytes. The BLV-associated antigens were detected as early as 3 hours, with maximum antigen production occurring at 18 to 24 hours after incubation. These results indicate that culturing of lymphocytes in vitro is necessary for the expression of the virus.", "contents": "Bovine leukemia virus-associated antigens in lymphocyte cultures. Short-term lymphocyte cultures from bovine leukemia virus (BLV)-infected cattle were tested for BLV-associated antigens at various times after incubation. Several immunologic methods were used, including fluorescent antibody tests, immunodiffusion, and radial immunodiffusion. Antigens were not detected in uncultured lymphocytes. The BLV-associated antigens were detected as early as 3 hours, with maximum antigen production occurring at 18 to 24 hours after incubation. These results indicate that culturing of lymphocytes in vitro is necessary for the expression of the virus."}
{"id": "PMID:201203", "title": "Effect of estrogens and calcium carbonate on bone loss in postmenopausal women.", "content": "Sixty postmenopausal women were placed in three groups--control, sex hormone-treated, and CaCO3-treated--and followed for 2 years. Skeletal mass decreased by 1.18%/year in the control group, 0.15%/year in the hormone group, and 0.22%/year in the CaCO3 group by radiogrammetry; and 2.88%/year in the control group, 0.73%/year in the hormone group, and 1.83%/year in the CaCO3 group by photon absorptiometry. The treatment groups differed significantly from the control group except for photon absorptiometry in the CaCO3 group. Bone accretion and resorption decreased in the treatment groups as measured by calcium tracer kinetics, resorption more so than accretion. We conclude that [1] these techniques are sufficiently sensitive to detect age-related bone loss; [2] postmenopausal sex-hormone replacement measurably decreases age-related bone loss by suppressing bone turnover, resorption more than accretion; and [3] calcium supplements produce the same effect but at the dose we used were slightly less effective.", "contents": "Effect of estrogens and calcium carbonate on bone loss in postmenopausal women. Sixty postmenopausal women were placed in three groups--control, sex hormone-treated, and CaCO3-treated--and followed for 2 years. Skeletal mass decreased by 1.18%/year in the control group, 0.15%/year in the hormone group, and 0.22%/year in the CaCO3 group by radiogrammetry; and 2.88%/year in the control group, 0.73%/year in the hormone group, and 1.83%/year in the CaCO3 group by photon absorptiometry. The treatment groups differed significantly from the control group except for photon absorptiometry in the CaCO3 group. Bone accretion and resorption decreased in the treatment groups as measured by calcium tracer kinetics, resorption more so than accretion. We conclude that [1] these techniques are sufficiently sensitive to detect age-related bone loss; [2] postmenopausal sex-hormone replacement measurably decreases age-related bone loss by suppressing bone turnover, resorption more than accretion; and [3] calcium supplements produce the same effect but at the dose we used were slightly less effective."}
{"id": "PMID:201204", "title": "Swine influenza and the news media.", "content": "Press coverage of the swine influenza inoculation campaign was generally superficial and marked by a \"body count\" mentality, but it was rarely inaccurate or sensationa, as has frequently been assumed. A study of coverage in 19 daily newspapers, the three television networks, and a wire service shows that the best work was done by science and medical writers on major metropolitan newspaper. Television newsmen and wire reporters were unprepared for a story of such complexity. A weak press relations effort by the Center for Disease Control and other public health agencies contributed to the public's confusion and upset professionals in the press. A better understanding by doctors of how the press works and closer relations between the medical community and the press can improve coverage of future public health programs.", "contents": "Swine influenza and the news media. Press coverage of the swine influenza inoculation campaign was generally superficial and marked by a \"body count\" mentality, but it was rarely inaccurate or sensationa, as has frequently been assumed. A study of coverage in 19 daily newspapers, the three television networks, and a wire service shows that the best work was done by science and medical writers on major metropolitan newspaper. Television newsmen and wire reporters were unprepared for a story of such complexity. A weak press relations effort by the Center for Disease Control and other public health agencies contributed to the public's confusion and upset professionals in the press. A better understanding by doctors of how the press works and closer relations between the medical community and the press can improve coverage of future public health programs."}
{"id": "PMID:201207", "title": "Blood chemistry and lipid profiles of elite distance runners.", "content": "In summary, we conclude that the analysis of the blood profiles of elite runners offers no explanation for their superior fitness of physical ability when compared to the good runners. Selected enzymes related to cellular or tissue damage may be elevated in distance runners and could be classified as abnormal on routine clinical evaluation if unaware of their physical lifestyles. It is also important to note that certain blood profile parameters, especially the hematocrit, could be classified as abnormally low. Finally, the high degree of daily physical activity performed by the elite runners and good runners appears to be associated with a lipoprotein profile consistent with a low risk for development of coronary artery disease manifestations. These profiles persist despite increasing age in active running males.", "contents": "Blood chemistry and lipid profiles of elite distance runners. In summary, we conclude that the analysis of the blood profiles of elite runners offers no explanation for their superior fitness of physical ability when compared to the good runners. Selected enzymes related to cellular or tissue damage may be elevated in distance runners and could be classified as abnormal on routine clinical evaluation if unaware of their physical lifestyles. It is also important to note that certain blood profile parameters, especially the hematocrit, could be classified as abnormally low. Finally, the high degree of daily physical activity performed by the elite runners and good runners appears to be associated with a lipoprotein profile consistent with a low risk for development of coronary artery disease manifestations. These profiles persist despite increasing age in active running males."}
{"id": "PMID:201209", "title": "Plasma lipoprotein distributions in male and female runners.", "content": "Recent studies have shown a consistent association between relatively low plasma concentrations of high-density lipoprotein (HDL) cholesterol and increased risk of coronary heart disease. A cross-sectional comparison was made of the distribution of plasma lipids and lipoproteins in groups of 41 male and 43 female long distance runners versus larger control groups matched for age and sex, randomly selected from northern California towns. The runners showed modestly lower total cholesterol concentrations, while their triglyceride levels were only 50% of control. HDL-cholesterol was higher in runners than controls (75 +/- 14 vs 56 +/- 14 mg/100 ml for women; 64 +/- 13 vs 43 +/- 10 for men), while low-density lipoprotein cholesterol was lower (113 +/- 33 vs 124 +/- 34 for women; 125 +/- 21 vs 139 +/- 32 for men). All differences were statistically significant (p less than 0.05), and only partially attributable to known factors other than high physical activity level. Since the runners were predominantly normotensive, relatively lean, and exclusively nonsmokers, they appear to constitute a remarkably favored group with respect to risk of cardiovascular disease.", "contents": "Plasma lipoprotein distributions in male and female runners. Recent studies have shown a consistent association between relatively low plasma concentrations of high-density lipoprotein (HDL) cholesterol and increased risk of coronary heart disease. A cross-sectional comparison was made of the distribution of plasma lipids and lipoproteins in groups of 41 male and 43 female long distance runners versus larger control groups matched for age and sex, randomly selected from northern California towns. The runners showed modestly lower total cholesterol concentrations, while their triglyceride levels were only 50% of control. HDL-cholesterol was higher in runners than controls (75 +/- 14 vs 56 +/- 14 mg/100 ml for women; 64 +/- 13 vs 43 +/- 10 for men), while low-density lipoprotein cholesterol was lower (113 +/- 33 vs 124 +/- 34 for women; 125 +/- 21 vs 139 +/- 32 for men). All differences were statistically significant (p less than 0.05), and only partially attributable to known factors other than high physical activity level. Since the runners were predominantly normotensive, relatively lean, and exclusively nonsmokers, they appear to constitute a remarkably favored group with respect to risk of cardiovascular disease."}
{"id": "PMID:201211", "title": "[The value of therapeutic arteriography in the treatment of tympano-jugular glomus tumours (author's transl)].", "content": "In this article, the authors stress three fundamental points in the diagnostic and therapeutic angiographic study of tympano-jugular glomus tumours. The first basic concept is the need for complete right, left, internal carotid, vertebral and external carotid angiographic examination. The latter must be selective, regardless of the information provided by common carotid arteriography. This implies prior knowledge of the different arteries which may \"supply\" the gloumus tumour. The second basic point is the concept of vascular compartment, , often mutually independent and vascularised by a single pedicle. The juxtaposition of the different vascular compartments gives the exact size of the tumour. The third important point concerns embolisation carried out at the same time as diagnostic angiography. This is invariably indicated on a pre-operative basis, except in two circumstances: --when the glomus, tumour is small and situated close to the drum of the tympanum, its surgical excision posing no problem of haemostasis under these circumstances: --when radiotherapy is envisaged as treatment of the glomus tumour when surgery is impossible. In this case, embolisation is contraindicated for two reasons: -radiotherapy is more effective when blood flow is preserved; -the risks of necrosis are increased.", "contents": "[The value of therapeutic arteriography in the treatment of tympano-jugular glomus tumours (author's transl)]. In this article, the authors stress three fundamental points in the diagnostic and therapeutic angiographic study of tympano-jugular glomus tumours. The first basic concept is the need for complete right, left, internal carotid, vertebral and external carotid angiographic examination. The latter must be selective, regardless of the information provided by common carotid arteriography. This implies prior knowledge of the different arteries which may \"supply\" the gloumus tumour. The second basic point is the concept of vascular compartment, , often mutually independent and vascularised by a single pedicle. The juxtaposition of the different vascular compartments gives the exact size of the tumour. The third important point concerns embolisation carried out at the same time as diagnostic angiography. This is invariably indicated on a pre-operative basis, except in two circumstances: --when the glomus, tumour is small and situated close to the drum of the tympanum, its surgical excision posing no problem of haemostasis under these circumstances: --when radiotherapy is envisaged as treatment of the glomus tumour when surgery is impossible. In this case, embolisation is contraindicated for two reasons: -radiotherapy is more effective when blood flow is preserved; -the risks of necrosis are increased."}
{"id": "PMID:201212", "title": "Skeletal maturation of Hong Kong Chinese children in the first five years of life.", "content": "This report describes the skeletal maturity during the first five years of life of 492 Chinese children in Hong Kong in a longitudinal study. Hand-wrist radiographs taken half-yearly were assessed by the Tanner-Whitehouse method and rated according to the TW1 20-bone self-weighting maturity score. Skeletal age was in advance of chronological age in both sexes, but significantly more so in females, especially between 18 months and three years. The relationship of the skeletal maturation of these children to various socioeconomic factors is discussed, including the effect of preferential child rearing in favour of males.", "contents": "Skeletal maturation of Hong Kong Chinese children in the first five years of life. This report describes the skeletal maturity during the first five years of life of 492 Chinese children in Hong Kong in a longitudinal study. Hand-wrist radiographs taken half-yearly were assessed by the Tanner-Whitehouse method and rated according to the TW1 20-bone self-weighting maturity score. Skeletal age was in advance of chronological age in both sexes, but significantly more so in females, especially between 18 months and three years. The relationship of the skeletal maturation of these children to various socioeconomic factors is discussed, including the effect of preferential child rearing in favour of males."}
{"id": "PMID:201213", "title": "Skeletal maturity of the hand and wrist in Japanese children by the TW2 method.", "content": "The skeletal maturity of Japanese children aged 0--18 years in Tokyo was compared with that of British children by the TW2 method. The skeletal age was the same as or less than the chronological age until 8 years. Thereafter, it was in advance of chronological age until 18 years in boys and 15 years in girls. The hand and wrist bones completed maturation about the same time in both Japanese and British children, at the age of 18 years in boys and 16 years in girls.", "contents": "Skeletal maturity of the hand and wrist in Japanese children by the TW2 method. The skeletal maturity of Japanese children aged 0--18 years in Tokyo was compared with that of British children by the TW2 method. The skeletal age was the same as or less than the chronological age until 8 years. Thereafter, it was in advance of chronological age until 18 years in boys and 15 years in girls. The hand and wrist bones completed maturation about the same time in both Japanese and British children, at the age of 18 years in boys and 16 years in girls."}
{"id": "PMID:201214", "title": "Polymyxin B and rifampin: new regimen for multiresistant Serratia marcescens infections.", "content": "Polymyxin B and rifampin were given to 12 patients with multi-drug-resistant nosocomial Serratia marcescens infections. Eight cures were achieved; drug hepatotoxicity occurred once; one fatal suprainfection was encountered; and two patients died during therapy of causes related to severe underlying illnesses. Polymyxin B and rifampin were uniformly synergistic in vitro against the infecting strains and against 40 additional clinical isolates of S. marcescens.", "contents": "Polymyxin B and rifampin: new regimen for multiresistant Serratia marcescens infections. Polymyxin B and rifampin were given to 12 patients with multi-drug-resistant nosocomial Serratia marcescens infections. Eight cures were achieved; drug hepatotoxicity occurred once; one fatal suprainfection was encountered; and two patients died during therapy of causes related to severe underlying illnesses. Polymyxin B and rifampin were uniformly synergistic in vitro against the infecting strains and against 40 additional clinical isolates of S. marcescens."}
{"id": "PMID:201215", "title": "Inactivation of enteric viruses in wastewater sludge through dewatering by evaporation.", "content": "The effect of dewatering on the inactivation rates of enteric viruses in sludge was determined. For this study, water was evaporated from seeded raw sludge at 21 degrees C, and the loss of viral plaque-forming units was measured. Initial results with poliovirus showed that recoverable infectivity gradually decreased with the loss of water until the solids content reached about 65%. When the solids content was increased from 65 to 83%, a further, more dramatic decrease in virus titer of greater than three orders of magnitude was observed. This loss of infectivity was due to irreversible inactivation of poliovirus because viral particles were found to have released their RNA molecules which were extensively degraded. Viral inactivation in these experiments may have been at least partially caused by the evaporation process itself because similar effects on poliovirus particles were observed in distilled water after only partial loss of water by evaporation. Coxsackievirus and reovirus were also found to be inactivated in sludge under comparable conditions, which suggests that dewatering by evaporation may be a feasible method of inactivating all enteric viruses in sludge.", "contents": "Inactivation of enteric viruses in wastewater sludge through dewatering by evaporation. The effect of dewatering on the inactivation rates of enteric viruses in sludge was determined. For this study, water was evaporated from seeded raw sludge at 21 degrees C, and the loss of viral plaque-forming units was measured. Initial results with poliovirus showed that recoverable infectivity gradually decreased with the loss of water until the solids content reached about 65%. When the solids content was increased from 65 to 83%, a further, more dramatic decrease in virus titer of greater than three orders of magnitude was observed. This loss of infectivity was due to irreversible inactivation of poliovirus because viral particles were found to have released their RNA molecules which were extensively degraded. Viral inactivation in these experiments may have been at least partially caused by the evaporation process itself because similar effects on poliovirus particles were observed in distilled water after only partial loss of water by evaporation. Coxsackievirus and reovirus were also found to be inactivated in sludge under comparable conditions, which suggests that dewatering by evaporation may be a feasible method of inactivating all enteric viruses in sludge."}
{"id": "PMID:201216", "title": "Agar plate screening procedure for cyclic adenosine 3',5'-monophosphate and inhibitors of cyclic nucleotide phosphodiesterase.", "content": "A procedure is described for the semiquantitative measurement of cyclic adenosine 3',5'-monophosphate (cAMP) and detection of inhibitors of cAMP phosphodiesterase by an agar plate test. The assay organism was an adenyl cyclase-deficient mutant derived from Escherichia coli HfrH. In the presence of an acid base indicator, acid production from barbohydrate metabolism was observed as a yellow zone around filter paper disks containing cAMP. Since yellow zone formation reflects the presence of cAMP, a phosphodiesterase inhibitor can be detected indirectly by the presence of a yellow zone on assay plates from a reaction mixture of an inhibitor, phosphodiesterase, and cAMP. Three known cyclic nucleotide phosphodiesterase inhibitors were active against beef brain phosphodiesterase in this system.", "contents": "Agar plate screening procedure for cyclic adenosine 3',5'-monophosphate and inhibitors of cyclic nucleotide phosphodiesterase. A procedure is described for the semiquantitative measurement of cyclic adenosine 3',5'-monophosphate (cAMP) and detection of inhibitors of cAMP phosphodiesterase by an agar plate test. The assay organism was an adenyl cyclase-deficient mutant derived from Escherichia coli HfrH. In the presence of an acid base indicator, acid production from barbohydrate metabolism was observed as a yellow zone around filter paper disks containing cAMP. Since yellow zone formation reflects the presence of cAMP, a phosphodiesterase inhibitor can be detected indirectly by the presence of a yellow zone on assay plates from a reaction mixture of an inhibitor, phosphodiesterase, and cAMP. Three known cyclic nucleotide phosphodiesterase inhibitors were active against beef brain phosphodiesterase in this system."}
{"id": "PMID:201217", "title": "Fatal cytomegalic inclusion disease. Associated skin manifestations in a renal transplant patient.", "content": "A case of cytomegalovirus-induced vasculitis led to skin ulcerations in a renal transplant patient. Light and electron microscopy revealed inclusion bodies and viral particles, respectively, characteristic of cytomegalovirus. To our knowledge, this is the first report of cytomegalovirus-induced vasculitis producing skin ulcerations, and it illustrates another of the protean manifestations of cytomegalovirus inclusion disease that may have important clinical implications.", "contents": "Fatal cytomegalic inclusion disease. Associated skin manifestations in a renal transplant patient. A case of cytomegalovirus-induced vasculitis led to skin ulcerations in a renal transplant patient. Light and electron microscopy revealed inclusion bodies and viral particles, respectively, characteristic of cytomegalovirus. To our knowledge, this is the first report of cytomegalovirus-induced vasculitis producing skin ulcerations, and it illustrates another of the protean manifestations of cytomegalovirus inclusion disease that may have important clinical implications."}
{"id": "PMID:201218", "title": "DNA-binding proteins of psoriatic scales. I. Isolation by affinity chromatography and characterisation by SDS slab gel electrophoresis.", "content": "DNA binding proteins (DBP) are shown to be engaged in the regulatory functions of the genome. Since the accelerated epidermopoesis in psoriasis indicates changed gene activities, the examination of DBP possible could help to clarify the pathological processes. Psoriatic scales were used to elaborate the method. DBP was isolated from a protein extract by affinity chromatography with DNA-cellulose according to Alberts et al. About 3-5% of postribosomal crude protein (PCP) extract had an affinity to DNA. The separation of DBP on SDS polyacrylamide slab gels showed a characteristic spectrum of proteins with molecular weights from 12.7 to 150 X 10(3) daltons. The protein band spectrum of the concentrated DBP fraction was different from that of the crude extract. These observations show the isolated DBP to represent an own group of water soluble proteins with DNA binding abilities.", "contents": "DNA-binding proteins of psoriatic scales. I. Isolation by affinity chromatography and characterisation by SDS slab gel electrophoresis. DNA binding proteins (DBP) are shown to be engaged in the regulatory functions of the genome. Since the accelerated epidermopoesis in psoriasis indicates changed gene activities, the examination of DBP possible could help to clarify the pathological processes. Psoriatic scales were used to elaborate the method. DBP was isolated from a protein extract by affinity chromatography with DNA-cellulose according to Alberts et al. About 3-5% of postribosomal crude protein (PCP) extract had an affinity to DNA. The separation of DBP on SDS polyacrylamide slab gels showed a characteristic spectrum of proteins with molecular weights from 12.7 to 150 X 10(3) daltons. The protein band spectrum of the concentrated DBP fraction was different from that of the crude extract. These observations show the isolated DBP to represent an own group of water soluble proteins with DNA binding abilities."}
{"id": "PMID:201219", "title": "DNA-binding proteins of psoriatic scales. II. DNA-Affinity of the three characteristic proteins increased in the water soluble extract of psoriatic scales.", "content": "The disc-electrophoretic pattern of a water soluble protein extract of psoriatic scales contains three characteristic proteins. They appear in higher amounts in psoriatic scales compared to normal human stratum corneum. Assuming that these proteins have any functional implication at DNA, their possible correlation to DNA-binding proteins (DBP) of psoriatic scales was examined. The disc-electrophoretic spectrum of DBP was compared with the protein profile of crude extract. However, no protein of DBP fraction correlated with one of the three characteristic proteins present in a water soluble extract. This signifies these proteins to be more a metabolically enriched product than proteins of chromosomal origin.", "contents": "DNA-binding proteins of psoriatic scales. II. DNA-Affinity of the three characteristic proteins increased in the water soluble extract of psoriatic scales. The disc-electrophoretic pattern of a water soluble protein extract of psoriatic scales contains three characteristic proteins. They appear in higher amounts in psoriatic scales compared to normal human stratum corneum. Assuming that these proteins have any functional implication at DNA, their possible correlation to DNA-binding proteins (DBP) of psoriatic scales was examined. The disc-electrophoretic spectrum of DBP was compared with the protein profile of crude extract. However, no protein of DBP fraction correlated with one of the three characteristic proteins present in a water soluble extract. This signifies these proteins to be more a metabolically enriched product than proteins of chromosomal origin."}
{"id": "PMID:201221", "title": "Peripheral vascular actions of alpha-methyldopa in the dog.", "content": "The aim of these study was to investigate peripheral vascular actions of alpha-methyldopa. The following experimental procedures were used: hind-limb of the dog perfused with the animals own blood or with Krebs solution; nictitating membrane of the dog; isolated and perfused segments of the saphenous vein of the dog; superfused strips of the saphenous vein of the dog. In these preparations, effects of alpha-methyldopa on responses elicited by electrical stimulation and on release of 3H-noradrenaline were studied. In dogs pretreated with alpha-methyldopa (200 mg/kg, i.v., 36, 24 and 4 hr before the experiment) contractions of the nictitating membrane caused by cervical sympathetic electrical stimulation were markedly reduced: however, the frequency--response curve to stimulation in the hind-limb and responsiveness to noradrenaline were not significantly different of controls. Perfusion of the hind-limb with Krebs containing alpha-methyldopa (2.2 mM) resulted in a significant reduction of perfusion pressure responses to lumbar sympathetic electrical stimulation with augmented responsiveness to exogenous noradrenaline. Similar results were obtained in in vitro experiments. Effects of alpha-methyldopa were not prevented by cocaine nor by inhibition of decarboxylase by Ro 4-4602 (D,L-serine,2-(2,3,4-,trihydroxybenzyl) hydrazine hydrochloride). Alpha-methyldopa depresses the release of tritiated compounds evoked by electrical stimulation, in saphenous vein strips. This suggests that inhibition of transmitter release could be an important factor to understand peripheral actions of alpha-methyldopa.", "contents": "Peripheral vascular actions of alpha-methyldopa in the dog. The aim of these study was to investigate peripheral vascular actions of alpha-methyldopa. The following experimental procedures were used: hind-limb of the dog perfused with the animals own blood or with Krebs solution; nictitating membrane of the dog; isolated and perfused segments of the saphenous vein of the dog; superfused strips of the saphenous vein of the dog. In these preparations, effects of alpha-methyldopa on responses elicited by electrical stimulation and on release of 3H-noradrenaline were studied. In dogs pretreated with alpha-methyldopa (200 mg/kg, i.v., 36, 24 and 4 hr before the experiment) contractions of the nictitating membrane caused by cervical sympathetic electrical stimulation were markedly reduced: however, the frequency--response curve to stimulation in the hind-limb and responsiveness to noradrenaline were not significantly different of controls. Perfusion of the hind-limb with Krebs containing alpha-methyldopa (2.2 mM) resulted in a significant reduction of perfusion pressure responses to lumbar sympathetic electrical stimulation with augmented responsiveness to exogenous noradrenaline. Similar results were obtained in in vitro experiments. Effects of alpha-methyldopa were not prevented by cocaine nor by inhibition of decarboxylase by Ro 4-4602 (D,L-serine,2-(2,3,4-,trihydroxybenzyl) hydrazine hydrochloride). Alpha-methyldopa depresses the release of tritiated compounds evoked by electrical stimulation, in saphenous vein strips. This suggests that inhibition of transmitter release could be an important factor to understand peripheral actions of alpha-methyldopa."}
{"id": "PMID:201222", "title": "Norepinephrine-stimulated cyclic AMP accumulation in brain slices in vitro after serotonin depletion or chronic administration of selective amine reuptake inhibitors.", "content": "These experiments demonstrate that altering serotonin availability in vivo does not influence the interaction of norepinephrine with adenylate cyclase in vitro. Neither reducing serotonin levels (parachloroamphetamine) nor increasing the availability of serotonin by blocking its reuptake (fluoxetine) affect the norepinephrine-induced elevation of cyclic AMP in slices of the limbic forebrain of rats. However, increasing norepinephrine availability by chronic administration of desipramine, a norepinephrine reuptake inhibitor, reduces cyclic AMP synthesis in the limbic forebrain. However, it is doubtful that blockade of norepinephrine reuptake alone accounts for the reduction in receptor sensitivity produced by desipramine since chronic administration of a new norepinephrine reuptake inhibitor, nisoxetine, does not decrease cyclic AMP accumulation.", "contents": "Norepinephrine-stimulated cyclic AMP accumulation in brain slices in vitro after serotonin depletion or chronic administration of selective amine reuptake inhibitors. These experiments demonstrate that altering serotonin availability in vivo does not influence the interaction of norepinephrine with adenylate cyclase in vitro. Neither reducing serotonin levels (parachloroamphetamine) nor increasing the availability of serotonin by blocking its reuptake (fluoxetine) affect the norepinephrine-induced elevation of cyclic AMP in slices of the limbic forebrain of rats. However, increasing norepinephrine availability by chronic administration of desipramine, a norepinephrine reuptake inhibitor, reduces cyclic AMP synthesis in the limbic forebrain. However, it is doubtful that blockade of norepinephrine reuptake alone accounts for the reduction in receptor sensitivity produced by desipramine since chronic administration of a new norepinephrine reuptake inhibitor, nisoxetine, does not decrease cyclic AMP accumulation."}
{"id": "PMID:201223", "title": "Isoprenaline-induced release of cyclic adenosine 3',5'-monophosphate by the left ventricle in the anaesthetized intact dog.", "content": "The ability of the heart to release cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the coronary venous blood was examined in closed-chest anaesthetized dogs before and during an infusion of isoprenaline. Before the infusion, no difference was observed between the cyclic AMP plasma levels in the aortic and coronary sinus blood. During the infusion, significant coronary veno-arterial differences in nucleotide concentration were observed despite a considerable elevation of the cyclic AMP plasma level in the aortic blood.", "contents": "Isoprenaline-induced release of cyclic adenosine 3',5'-monophosphate by the left ventricle in the anaesthetized intact dog. The ability of the heart to release cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the coronary venous blood was examined in closed-chest anaesthetized dogs before and during an infusion of isoprenaline. Before the infusion, no difference was observed between the cyclic AMP plasma levels in the aortic and coronary sinus blood. During the infusion, significant coronary veno-arterial differences in nucleotide concentration were observed despite a considerable elevation of the cyclic AMP plasma level in the aortic blood."}
{"id": "PMID:201224", "title": "A unique multisystemic syndrome of unknown origin.", "content": "A unique multisystemic syndrome of polyneuropathy, anasarca, polycythemia, pigmentation, and endocrinopathy that occurred outside of Japan is reported, along with the results of postmortem examination. A review of the literature on this syndrome is presented, and the possible etiological considerations are discussed.", "contents": "A unique multisystemic syndrome of unknown origin. A unique multisystemic syndrome of polyneuropathy, anasarca, polycythemia, pigmentation, and endocrinopathy that occurred outside of Japan is reported, along with the results of postmortem examination. A review of the literature on this syndrome is presented, and the possible etiological considerations are discussed."}
{"id": "PMID:201220", "title": "Effect of phosgene on rat lungs after single high-level exposure.", "content": "Rats were exposed under static conditions to phosgene at concentrations within the LCt50 range and above. Lungs were removed at various postexposure intervals. Degrees of pulmonary edema were estimated by increases in percentage of water in the lungs of exposed groups as opposed to control animals. Lungs were fractionated into four major subcellular organelle fractions: nuclear debris, mitochondrial-lysosomal, microsomal, and soluble (cytoplasmic). Activities of p-nitrophenyl phosphatase, cytochrome C oxidase, ATP'ase, and LDH within these fractions were decreased after phosgene exposure. There was a concomitant increase in serum LDH levels. One possible mechanism that may play a role in phosgene damage can be associated with either inhibition or loss of enzyme activities from the lung.", "contents": "Effect of phosgene on rat lungs after single high-level exposure. Rats were exposed under static conditions to phosgene at concentrations within the LCt50 range and above. Lungs were removed at various postexposure intervals. Degrees of pulmonary edema were estimated by increases in percentage of water in the lungs of exposed groups as opposed to control animals. Lungs were fractionated into four major subcellular organelle fractions: nuclear debris, mitochondrial-lysosomal, microsomal, and soluble (cytoplasmic). Activities of p-nitrophenyl phosphatase, cytochrome C oxidase, ATP'ase, and LDH within these fractions were decreased after phosgene exposure. There was a concomitant increase in serum LDH levels. One possible mechanism that may play a role in phosgene damage can be associated with either inhibition or loss of enzyme activities from the lung."}
{"id": "PMID:201226", "title": "[Ultrastructural-morphometric investigations on liver biopsies--the influence of oral contraceptives on the human liver (author's transl)].", "content": "Liver biopsies from 12 healthy women were investigated morphometrically--according to the methods of Weibel (1969). All women had taken an oral contraceptive agent during 2 til 76 months. The evaluated stereological datas were compared with base-line dates for normal human liver biopsies, which were elaborated in a previous investigation (Roessner et al., 1977). Statistical analysis was performed on an IBM 360/50 computer system, including F- and student's t-test. In the liver biopsy-specimen from the women, which were on oral contraceptives, the volume-density of lysosomes per ml hepatocytes shows a pronounced, significant (p less than 0.001) increase. A moderate increase of cytoplasm is combined with decrease of nuclei-volume. The surface-densities of the rough and smooth endoplasmatic reticulum do not differ significantly from the datas calculated from normal human liver biopsies. All other datas too demonstrate that there are no striking changes in the ultrastructure of human liver, caused by oral contraceptives. Functional alterations however can not be excluded.", "contents": "[Ultrastructural-morphometric investigations on liver biopsies--the influence of oral contraceptives on the human liver (author's transl)]. Liver biopsies from 12 healthy women were investigated morphometrically--according to the methods of Weibel (1969). All women had taken an oral contraceptive agent during 2 til 76 months. The evaluated stereological datas were compared with base-line dates for normal human liver biopsies, which were elaborated in a previous investigation (Roessner et al., 1977). Statistical analysis was performed on an IBM 360/50 computer system, including F- and student's t-test. In the liver biopsy-specimen from the women, which were on oral contraceptives, the volume-density of lysosomes per ml hepatocytes shows a pronounced, significant (p less than 0.001) increase. A moderate increase of cytoplasm is combined with decrease of nuclei-volume. The surface-densities of the rough and smooth endoplasmatic reticulum do not differ significantly from the datas calculated from normal human liver biopsies. All other datas too demonstrate that there are no striking changes in the ultrastructure of human liver, caused by oral contraceptives. Functional alterations however can not be excluded."}
{"id": "PMID:201227", "title": "[Association between HSV 2 antigen and colpocytologic finding (author's transl)].", "content": "Prophylactic gynecologic examinations were performed in 1440 women using colposcopy and vaginalcytology. A search for HSV antigen in cervical cells was performed HSV antigen was found in 12% of Pap I--II smears, in 41% of Pap III smears and in all cases of Pap IV--V. It is suggested that there is a probable association between HSV 2 and cervical cancer.", "contents": "[Association between HSV 2 antigen and colpocytologic finding (author's transl)]. Prophylactic gynecologic examinations were performed in 1440 women using colposcopy and vaginalcytology. A search for HSV antigen in cervical cells was performed HSV antigen was found in 12% of Pap I--II smears, in 41% of Pap III smears and in all cases of Pap IV--V. It is suggested that there is a probable association between HSV 2 and cervical cancer."}
{"id": "PMID:201225", "title": "[Hyperparathyroidism in deficiency rickets. Changes after vitamin therapy].", "content": "The study concerned 16 cases of deficiency rickets observed over 3 years. The level of serum parathyroid (IPTH) hormone was always increased in the late stages of rickets, but was normal in 3 cases of early rickets with hypocalcaemia and monophosphataemia. There was no statistical correlation between the level of IPTH and monophosphataemia. There was no statistical correlation between the level of IPTH and calcaemia. After vitamin D-therapy, the levels if IPTH returned to normal in 5 to 21 days in most cases. No obvious difference was noted in this evolution between children treated by vitamin D2 and 25 OH D. The excretion of urinary cyclic adenosine monophosphate decreases in parallel with blood IPTH.", "contents": "[Hyperparathyroidism in deficiency rickets. Changes after vitamin therapy]. The study concerned 16 cases of deficiency rickets observed over 3 years. The level of serum parathyroid (IPTH) hormone was always increased in the late stages of rickets, but was normal in 3 cases of early rickets with hypocalcaemia and monophosphataemia. There was no statistical correlation between the level of IPTH and monophosphataemia. There was no statistical correlation between the level of IPTH and calcaemia. After vitamin D-therapy, the levels if IPTH returned to normal in 5 to 21 days in most cases. No obvious difference was noted in this evolution between children treated by vitamin D2 and 25 OH D. The excretion of urinary cyclic adenosine monophosphate decreases in parallel with blood IPTH."}
{"id": "PMID:201230", "title": "[Neurogenic stomach neoplasms induced by nitrosomethylures in Syrian hamsters].", "content": "In the experiment with inoculation of N-nitroso-N-methylurea (a maximum total dose of 7.5 mg) to Syrian hamsters, tumors developed in 20 out of 25 animals surviving the time of the occurrence of the first tumor (31 weeks). Out of 35 tumors 17 developed at the site of inoculation: in the left cheek pouch (of them 12 embryonal rhabdomyoblastomas), 11 in the stomach (of them 6 neurogenic), and 7 in other organs (skin, liver, adrenals, hemopoietic system). The paper describes the histological pattern of 6 neurogenic tumors of the stomach in which all the elements of the nervous system have been found: ganglionic cells, neuroglia, and nerve stems. On the basis of some signs the authors classify these tumors as malignant.", "contents": "[Neurogenic stomach neoplasms induced by nitrosomethylures in Syrian hamsters]. In the experiment with inoculation of N-nitroso-N-methylurea (a maximum total dose of 7.5 mg) to Syrian hamsters, tumors developed in 20 out of 25 animals surviving the time of the occurrence of the first tumor (31 weeks). Out of 35 tumors 17 developed at the site of inoculation: in the left cheek pouch (of them 12 embryonal rhabdomyoblastomas), 11 in the stomach (of them 6 neurogenic), and 7 in other organs (skin, liver, adrenals, hemopoietic system). The paper describes the histological pattern of 6 neurogenic tumors of the stomach in which all the elements of the nervous system have been found: ganglionic cells, neuroglia, and nerve stems. On the basis of some signs the authors classify these tumors as malignant."}
{"id": "PMID:201231", "title": "[Papillomatosis of the distal part of the common bile duct associated with adenomatosis of its wall].", "content": "A case of papillomatosis of the distal part of the common bile duct in combination with adenomatosis of its wall in a patient aged thirty nine is described. On the basis of data from the literature and their own observations, the authors present different opinions concerning the mechanism of the development of bile duct papillomatosis.", "contents": "[Papillomatosis of the distal part of the common bile duct associated with adenomatosis of its wall]. A case of papillomatosis of the distal part of the common bile duct in combination with adenomatosis of its wall in a patient aged thirty nine is described. On the basis of data from the literature and their own observations, the authors present different opinions concerning the mechanism of the development of bile duct papillomatosis."}
{"id": "PMID:201232", "title": "Hallervorden-Spatz syndrome.", "content": "Two siblings with Hallervorden-Spatz syndrome showed striking homotypism and homochronism. Neuropathologic examination and electron microscopic studies were done; neutron activation analysis showed an increase in the uptake of iron in the basal ganglia. Of particular relevance is the application of radioactive iron studies in the clinical course of this syndrome. These studies disclosed an increase in the uptake of iron in the area of the basal ganglia in one sibling and in another isolated patient. This procedure will be helpful toward the clinical diagnosis.", "contents": "Hallervorden-Spatz syndrome. Two siblings with Hallervorden-Spatz syndrome showed striking homotypism and homochronism. Neuropathologic examination and electron microscopic studies were done; neutron activation analysis showed an increase in the uptake of iron in the basal ganglia. Of particular relevance is the application of radioactive iron studies in the clinical course of this syndrome. These studies disclosed an increase in the uptake of iron in the area of the basal ganglia in one sibling and in another isolated patient. This procedure will be helpful toward the clinical diagnosis."}
{"id": "PMID:201233", "title": "Demonstration of hormonal activity of a glomus juglare tumour by catecholamine determination.", "content": "For the first time the hormonal activity of a glomus jugulare tumour, clinically manifest by intermitting hypertension, could be demonstrated by catecholamine level determination in blood. Endocrinological and diagnostic aspects concerned to the differential diagnosis of the hypertension in these patients are discussed.", "contents": "Demonstration of hormonal activity of a glomus juglare tumour by catecholamine determination. For the first time the hormonal activity of a glomus jugulare tumour, clinically manifest by intermitting hypertension, could be demonstrated by catecholamine level determination in blood. Endocrinological and diagnostic aspects concerned to the differential diagnosis of the hypertension in these patients are discussed."}
{"id": "PMID:201234", "title": "[Clinical and morphological findings in Tangier disease (hypo-alpha-lipoporteinaemia) and its ENT-significance (author's transl)].", "content": "The report deals with the first three cases of Tangier disease (Hypo-alpha-Lipoproteinaemia) observed in Germany. This rare metabolic disorder is distinguished by a diminution of HDL-Lipoproteins in serum and a lipid storage in histiocytes. The prominent symptom is the orange yellow discolouration of hyperplastic tonsills and adenoids; further symptoms of the disease generally are various, the development is little typical. The morphological substrat of the deranged fat metabolism is cholesteryl ester storage in the reticuloendothelial system, smooth muscle cells, pericytes and Schwann cells of peripheral nerves. M. Tangier can be differentiated from other lysosomal defects by ultrastructural and chemical parameters, it seems to have a autosomal recessive inheritance. It is the ENT-specialist, who can establish an early diagnosis of this disease, provided he is aware of its clinical features.", "contents": "[Clinical and morphological findings in Tangier disease (hypo-alpha-lipoporteinaemia) and its ENT-significance (author's transl)]. The report deals with the first three cases of Tangier disease (Hypo-alpha-Lipoproteinaemia) observed in Germany. This rare metabolic disorder is distinguished by a diminution of HDL-Lipoproteins in serum and a lipid storage in histiocytes. The prominent symptom is the orange yellow discolouration of hyperplastic tonsills and adenoids; further symptoms of the disease generally are various, the development is little typical. The morphological substrat of the deranged fat metabolism is cholesteryl ester storage in the reticuloendothelial system, smooth muscle cells, pericytes and Schwann cells of peripheral nerves. M. Tangier can be differentiated from other lysosomal defects by ultrastructural and chemical parameters, it seems to have a autosomal recessive inheritance. It is the ENT-specialist, who can establish an early diagnosis of this disease, provided he is aware of its clinical features."}
{"id": "PMID:201239", "title": "Comparisons of synthetic 1-18 ACTH (Organon 2001) and 1-39 ACTH of animal origin in human subjects.", "content": "The studies in human subjects herein reported provide data on the relative effects of 1-18 ACTH (Organon 2001) and commercial 1-39 ACTH of animal origin on plasma cortisol, serum non-esterified fatty acids, and certain urinary steroids.", "contents": "Comparisons of synthetic 1-18 ACTH (Organon 2001) and 1-39 ACTH of animal origin in human subjects. The studies in human subjects herein reported provide data on the relative effects of 1-18 ACTH (Organon 2001) and commercial 1-39 ACTH of animal origin on plasma cortisol, serum non-esterified fatty acids, and certain urinary steroids."}
{"id": "PMID:201240", "title": "Alterations of pulmonary vascular resistance and pulmonary cyclic nucleotide metabolism in the hypoxic pig.", "content": "Hypoxia leads to an elevation of the pulmonary vascular resistance (pvR) in pigs. This alteration of the hemodynamic was accompanied by a slight increase of intraparenchymatous concentrations of cyclic GMP (cGMP), while cycle AMP (cAMP) levels were not different from values, measured during normoxia. beta-adrenergic agents are potent inhibitors of the hypoxia induced vasoconstriction. This effect was associated with an increase of intraparenchymatous cAMP-concentrations and a decrease of cGMP-levels. The regression analysis between pvR versus the ratio cGMP/cAMP revealed a significant linear correlation. These data may indicate, that cAMP and cGMP are involved in hypoxia induced vasoconstriction and its pharmacological inhibition.", "contents": "Alterations of pulmonary vascular resistance and pulmonary cyclic nucleotide metabolism in the hypoxic pig. Hypoxia leads to an elevation of the pulmonary vascular resistance (pvR) in pigs. This alteration of the hemodynamic was accompanied by a slight increase of intraparenchymatous concentrations of cyclic GMP (cGMP), while cycle AMP (cAMP) levels were not different from values, measured during normoxia. beta-adrenergic agents are potent inhibitors of the hypoxia induced vasoconstriction. This effect was associated with an increase of intraparenchymatous cAMP-concentrations and a decrease of cGMP-levels. The regression analysis between pvR versus the ratio cGMP/cAMP revealed a significant linear correlation. These data may indicate, that cAMP and cGMP are involved in hypoxia induced vasoconstriction and its pharmacological inhibition."}
{"id": "PMID:201244", "title": "A comparison of cAMP phosphodiesterases in normal, malignant, and somatic cell hybrids.", "content": "Hybrids (PCM) between a malignant mouse lymphoma suspension cell line (P388F-36) and a normal Chinese hamster fibroblastic cell line (Ch23) have already been isolated in this laboratory. Investigations were carried out on the cAMP phospodiesterases of the parents and two of these hybrids--PCM2 and PCM3. PCM3 shows a rather unusual growth characteristic in that a considerable proportion of the cells exist at any one time either in suspension or only loosely attached to the substratum, the remaining cell population existing in a monolayer form. It was found that each cell line exhibited multiple forms of the enzyme with varying affinities for cAMP. Both parents, although different, contained high-, low-, and extra-high apparent Km forms of the enzyme. The hybrids exhibited characteristics of both parental systems but were different from each other. Neither hybrid exhibited a high-Km enzyme, but both exhibited two low-Km forms. There was also a slight variation between monolayer and suspension cells of PCM3 hybrid. An attempt has been made to explain these phenomena with respect to hybridization and the growth characteristics of the cells.", "contents": "A comparison of cAMP phosphodiesterases in normal, malignant, and somatic cell hybrids. Hybrids (PCM) between a malignant mouse lymphoma suspension cell line (P388F-36) and a normal Chinese hamster fibroblastic cell line (Ch23) have already been isolated in this laboratory. Investigations were carried out on the cAMP phospodiesterases of the parents and two of these hybrids--PCM2 and PCM3. PCM3 shows a rather unusual growth characteristic in that a considerable proportion of the cells exist at any one time either in suspension or only loosely attached to the substratum, the remaining cell population existing in a monolayer form. It was found that each cell line exhibited multiple forms of the enzyme with varying affinities for cAMP. Both parents, although different, contained high-, low-, and extra-high apparent Km forms of the enzyme. The hybrids exhibited characteristics of both parental systems but were different from each other. Neither hybrid exhibited a high-Km enzyme, but both exhibited two low-Km forms. There was also a slight variation between monolayer and suspension cells of PCM3 hybrid. An attempt has been made to explain these phenomena with respect to hybridization and the growth characteristics of the cells."}
{"id": "PMID:201245", "title": "An investigation of the homology of guanylate kinase isozymes in mammals and further evidence for multiple GUK gene loci.", "content": "Guanylate kinase in the red cells of 63 different mammalian species was studied by electrophoresis and multiple molecular forms of the enzyme were found in all species. Two species were investigated in more detail. Using molecular weight estimates as a criterion of homology, the fallow deer and the Chinese hamster were found to have isozymes that corresponded to isozyme e, f, and g of man. Variation in the guanylate kinase isozymes was detected in a small population of orangutans. Results suggested that isozymes a and b were monomeric and that they were the products of a gene locus, GUK1, different from the locus GUK3 which coded for isozymes e, f, and g. Products c and d of the presumptive GUK2 locus were not found in the orangutan.", "contents": "An investigation of the homology of guanylate kinase isozymes in mammals and further evidence for multiple GUK gene loci. Guanylate kinase in the red cells of 63 different mammalian species was studied by electrophoresis and multiple molecular forms of the enzyme were found in all species. Two species were investigated in more detail. Using molecular weight estimates as a criterion of homology, the fallow deer and the Chinese hamster were found to have isozymes that corresponded to isozyme e, f, and g of man. Variation in the guanylate kinase isozymes was detected in a small population of orangutans. Results suggested that isozymes a and b were monomeric and that they were the products of a gene locus, GUK1, different from the locus GUK3 which coded for isozymes e, f, and g. Products c and d of the presumptive GUK2 locus were not found in the orangutan."}
{"id": "PMID:201246", "title": "The reactions of 1,10-phenanthroline with yeast alcohol dehydrogenase.", "content": "Freshly prepared samples of yeast alcohol dehydrogenase (EC 1.1.1.1) were inhibited by 1,10-phenanthroline at pH 7.0 and 0 degrees C in a two-stage process. The first step appeared to be slowly established, but was rendered reversible by removal of reagent or by addition of excess Zn2+ ions. The second step was irreversible and was associated with the dissociation of the tetrameric enzyme. The presence of saturating concentrations of NAD+ or NADH promoted and enhanced inhibition by the slowly established reversible process, but prevented dissociation of the enzyme. For the incubation mixtures containing NAD+, removal of the 1,10-phenanthroline resulted in virtually complete recovery of activity, whereas, for the incubation mixtures containing NADH, removal of the reagent gave only partial re-activation. The presence of NAD+ and pyrazole, or NADH and acetamide, in incubation mixtures with the enzyme gave rise to ternary complexes that gave protection against both forms of inactivation by 1,10-phenanthroline. The results support the view that at least some of the Zn2+ ions associated with yeast alcohol dehydrogenase have a catalytic, as opposed to a purely structural, role.", "contents": "The reactions of 1,10-phenanthroline with yeast alcohol dehydrogenase. Freshly prepared samples of yeast alcohol dehydrogenase (EC 1.1.1.1) were inhibited by 1,10-phenanthroline at pH 7.0 and 0 degrees C in a two-stage process. The first step appeared to be slowly established, but was rendered reversible by removal of reagent or by addition of excess Zn2+ ions. The second step was irreversible and was associated with the dissociation of the tetrameric enzyme. The presence of saturating concentrations of NAD+ or NADH promoted and enhanced inhibition by the slowly established reversible process, but prevented dissociation of the enzyme. For the incubation mixtures containing NAD+, removal of the 1,10-phenanthroline resulted in virtually complete recovery of activity, whereas, for the incubation mixtures containing NADH, removal of the reagent gave only partial re-activation. The presence of NAD+ and pyrazole, or NADH and acetamide, in incubation mixtures with the enzyme gave rise to ternary complexes that gave protection against both forms of inactivation by 1,10-phenanthroline. The results support the view that at least some of the Zn2+ ions associated with yeast alcohol dehydrogenase have a catalytic, as opposed to a purely structural, role."}
{"id": "PMID:201247", "title": "Electron-paramagnetic-resonance studies on a photochemically produced species of horseradish peroxidase compound I.", "content": "Strong electron-paramagnetic-resonance signals in the g = 2.00 region were detected after irradiation of horseradish peroxidase Compound I at temperatures of 10 and 100 K. These signals establish the presence of new free-radical species in the peroxidase system. The new species are interpreted in terms of a haem-photosensitized oxidation of the protein's peptide groups close to the Compound I radical site. On warming to room temperature, the radicals decayed irreversibly to a species having a weak asymmetric electron-paramagnetic-resonance signal at 100 K, which could still be observed after incubation at room temperature for more than 1 h.", "contents": "Electron-paramagnetic-resonance studies on a photochemically produced species of horseradish peroxidase compound I. Strong electron-paramagnetic-resonance signals in the g = 2.00 region were detected after irradiation of horseradish peroxidase Compound I at temperatures of 10 and 100 K. These signals establish the presence of new free-radical species in the peroxidase system. The new species are interpreted in terms of a haem-photosensitized oxidation of the protein's peptide groups close to the Compound I radical site. On warming to room temperature, the radicals decayed irreversibly to a species having a weak asymmetric electron-paramagnetic-resonance signal at 100 K, which could still be observed after incubation at room temperature for more than 1 h."}
{"id": "PMID:201248", "title": "Hydroxylation of aromatic compounds by reduced nicotinamide-adenine dinucleotide and phenazine methosulphate requires hydrogen peroxide and hydroxyl radicals, but not superoxide.", "content": "1. A mixture of NADH and phenazine methosulphate hydroxylates aromatic compounds at acidic pH values. 2. Hydroxylation is inhibited by catalase and by scavengers of the hydroxyl radical (-OH) but not by superoxide dismutase. 3. It is concluded that neither O2 leads to nor HO2- is sufficiently reactive to hydroxylate aromatic rings.", "contents": "Hydroxylation of aromatic compounds by reduced nicotinamide-adenine dinucleotide and phenazine methosulphate requires hydrogen peroxide and hydroxyl radicals, but not superoxide. 1. A mixture of NADH and phenazine methosulphate hydroxylates aromatic compounds at acidic pH values. 2. Hydroxylation is inhibited by catalase and by scavengers of the hydroxyl radical (-OH) but not by superoxide dismutase. 3. It is concluded that neither O2 leads to nor HO2- is sufficiently reactive to hydroxylate aromatic rings."}
{"id": "PMID:201249", "title": "The equilibrium constant and the reversibility of the reaction catalysed by nicotinamide-adenine dinucleotide kinase from pigeon liver.", "content": "The reversibility of the NAD+ kinase reaction was established, and the kinetic parameters of the rate equation in the reverse direction were determined. The equilibrium constant of the reaction was determined by using the purified pigeon liver enzyme and radioactively labelled nicotinamide nucleotides. The relationship between kinetic parameters of the forward and reverse reactions is in reasonable agreement with the measured equilibrium constant. As expected from the proposed mechanism of action, the enzyme does not catalyse isotope exchange between NAD+ and NADP+ in the absence of ADP and ATP. Although homogeneous as judged by polyacrylamide-gel electrophoresis, the enzyme preparation exhibits ADP/ATP isotope-exchange activity which could not be separated from NAD+ kinase activity, but kinetic evidence suggests that this is probably due to a contaminant.", "contents": "The equilibrium constant and the reversibility of the reaction catalysed by nicotinamide-adenine dinucleotide kinase from pigeon liver. The reversibility of the NAD+ kinase reaction was established, and the kinetic parameters of the rate equation in the reverse direction were determined. The equilibrium constant of the reaction was determined by using the purified pigeon liver enzyme and radioactively labelled nicotinamide nucleotides. The relationship between kinetic parameters of the forward and reverse reactions is in reasonable agreement with the measured equilibrium constant. As expected from the proposed mechanism of action, the enzyme does not catalyse isotope exchange between NAD+ and NADP+ in the absence of ADP and ATP. Although homogeneous as judged by polyacrylamide-gel electrophoresis, the enzyme preparation exhibits ADP/ATP isotope-exchange activity which could not be separated from NAD+ kinase activity, but kinetic evidence suggests that this is probably due to a contaminant."}
{"id": "PMID:201258", "title": "The effect of cyclophosphamide on MSV-H oncogenesis.", "content": "The effect of cyclophosphamide on MSV-H oncogensis and the immune response of young mice has been investigated. A single, sublethal dose (100 and 50 mg/kg of cyclophosphamide) in 8-day-old mice given 24 h before or after MSV-H infection led to an earlier and lower incidence of tumours in comparison with controls infected only with MSV-H. The protective effect of cyclophosphamide, and the mechanism of action of both cyclophosphamide and MSV-H on the target cells, mesenchymal cells in rapid replication, as well the immunological implications of the findings are discussed.", "contents": "The effect of cyclophosphamide on MSV-H oncogenesis. The effect of cyclophosphamide on MSV-H oncogensis and the immune response of young mice has been investigated. A single, sublethal dose (100 and 50 mg/kg of cyclophosphamide) in 8-day-old mice given 24 h before or after MSV-H infection led to an earlier and lower incidence of tumours in comparison with controls infected only with MSV-H. The protective effect of cyclophosphamide, and the mechanism of action of both cyclophosphamide and MSV-H on the target cells, mesenchymal cells in rapid replication, as well the immunological implications of the findings are discussed."}
{"id": "PMID:201259", "title": "Assessment of inherent fluctuations of mitotic and labelling indices of human tumours.", "content": "A method is presented to evaluate the influence of statistical errors and inherent variation on the determination of mitotic and labelling indices of human tumours. In most of the experiments reported here, sufficient cells were counted to yield a statistical error which is small in comparison to the inherent differences in the proliferative indices, both between different sites in the same tumour and between different tumours of the same histological type. These inherent fluctuations are, theefore, a critical factor in cell kinetic studies of human tumours.", "contents": "Assessment of inherent fluctuations of mitotic and labelling indices of human tumours. A method is presented to evaluate the influence of statistical errors and inherent variation on the determination of mitotic and labelling indices of human tumours. In most of the experiments reported here, sufficient cells were counted to yield a statistical error which is small in comparison to the inherent differences in the proliferative indices, both between different sites in the same tumour and between different tumours of the same histological type. These inherent fluctuations are, theefore, a critical factor in cell kinetic studies of human tumours."}
{"id": "PMID:201260", "title": "Chromosome complement and SV40 transformation of cells from patients susceptible to malignant disease.", "content": "A comparative study has been made of fibroblasts obtained from patients with differing susceptibilities to malignant disease, both with respect to their chromosome complements and their transformation with SV40 virus. Fibroblasts from 2 Bloom's syndrome patients were found not to have raised SV40 transformation rates and no correlation was found between chromosome abnormality per se and transformation. Of 2 cell types with greatly increased rates, one was derived from a neurofibromatosis patient and the other from an A-T heterozygote. When SV40 DNA was employed as the transforming agent for the latter, the transformation rate was no longer raised.", "contents": "Chromosome complement and SV40 transformation of cells from patients susceptible to malignant disease. A comparative study has been made of fibroblasts obtained from patients with differing susceptibilities to malignant disease, both with respect to their chromosome complements and their transformation with SV40 virus. Fibroblasts from 2 Bloom's syndrome patients were found not to have raised SV40 transformation rates and no correlation was found between chromosome abnormality per se and transformation. Of 2 cell types with greatly increased rates, one was derived from a neurofibromatosis patient and the other from an A-T heterozygote. When SV40 DNA was employed as the transforming agent for the latter, the transformation rate was no longer raised."}
{"id": "PMID:201261", "title": "Secretion of prostaglandins as bone-resorbing agents by renal cortical carcinoma in culture.", "content": "Fragments of human renal carcinoma tissue have been co-cultured with mouse calvaria. In 9/13 cases significant bone resorption occurred whilst in no case did control kidney cause significant resorption. When bone resorption did occur, it could be reduced by inclusion of indomethacin in the culture medium. In some cases when theophylline was included in culture medium to prevent cyclic AMP breakdown, there was enhancement of tumour-induced bone resorption. Control studies without tumour showed that none of the experimental treatments had a direct effect on bone. Radioimmunoassay of prostaglandin E (PGE) levels in pooled culture media showed that tumour fragments produced appreciable amounts of PGE, and that this production was lowered by indomethacin and increased by theophylline. It is concluded that the bone resorption induced by these tumours is due to a prostaglandin, and that prostaglandin production may be controlled by changes in cyclic AMP metabolism.", "contents": "Secretion of prostaglandins as bone-resorbing agents by renal cortical carcinoma in culture. Fragments of human renal carcinoma tissue have been co-cultured with mouse calvaria. In 9/13 cases significant bone resorption occurred whilst in no case did control kidney cause significant resorption. When bone resorption did occur, it could be reduced by inclusion of indomethacin in the culture medium. In some cases when theophylline was included in culture medium to prevent cyclic AMP breakdown, there was enhancement of tumour-induced bone resorption. Control studies without tumour showed that none of the experimental treatments had a direct effect on bone. Radioimmunoassay of prostaglandin E (PGE) levels in pooled culture media showed that tumour fragments produced appreciable amounts of PGE, and that this production was lowered by indomethacin and increased by theophylline. It is concluded that the bone resorption induced by these tumours is due to a prostaglandin, and that prostaglandin production may be controlled by changes in cyclic AMP metabolism."}
{"id": "PMID:201263", "title": "The in vivo effects of quartz on rat thoracic lymph nodes.", "content": "The histological changes in the regional thoracic lymph nodes of rats exposed to silica dust by inhalation are recorded. A dual response is noted involving both inflammatory and immune mechanisms, resulting in a fibroblastic connective tissue reaction and a plasma-cell-macrophage interaction. It is proposed that the progressive silicotic lesions obstruct the lymphatic channels in the lymph nodes, thus interfering with the lymph drainage from the lung and aggravating the silicotic process in the lung itself.", "contents": "The in vivo effects of quartz on rat thoracic lymph nodes. The histological changes in the regional thoracic lymph nodes of rats exposed to silica dust by inhalation are recorded. A dual response is noted involving both inflammatory and immune mechanisms, resulting in a fibroblastic connective tissue reaction and a plasma-cell-macrophage interaction. It is proposed that the progressive silicotic lesions obstruct the lymphatic channels in the lymph nodes, thus interfering with the lymph drainage from the lung and aggravating the silicotic process in the lung itself."}
{"id": "PMID:201264", "title": "EMC viral infection of the coronary blood vessels in newborn mice: viral vasculitis.", "content": "The coronary arteries, veins and capillaries of newborn mice experimentally infected with encephalomyocarditis (EMC) virus were studied histologically and electronmicroscopically. Damage to these coronary vessels was patchy. Some lesions were extensive, particularly when adjacent to areas of myocardial damage. The histological findings consisted of swelling of adventitial and endothelial cells pyknosis, and polymorphonuclear leucocyte and round cell infiltration. Histological and ultrastructural changes occurred in all three layers of the vessels. EMC viral crystals were found electronmicroscopically in the adventitia of the coronary arteries and veins. Ultrastructural lesions typical of virocytonecrosis were frequently noted in association with viral crystals, establishing the viral etiology of the lesions. These findings lend support to the concept that the patchy atherosclerotic and arteriosclerotic lesions found in the coronary vessels of man may represent healed lesions of previous viral damage.", "contents": "EMC viral infection of the coronary blood vessels in newborn mice: viral vasculitis. The coronary arteries, veins and capillaries of newborn mice experimentally infected with encephalomyocarditis (EMC) virus were studied histologically and electronmicroscopically. Damage to these coronary vessels was patchy. Some lesions were extensive, particularly when adjacent to areas of myocardial damage. The histological findings consisted of swelling of adventitial and endothelial cells pyknosis, and polymorphonuclear leucocyte and round cell infiltration. Histological and ultrastructural changes occurred in all three layers of the vessels. EMC viral crystals were found electronmicroscopically in the adventitia of the coronary arteries and veins. Ultrastructural lesions typical of virocytonecrosis were frequently noted in association with viral crystals, establishing the viral etiology of the lesions. These findings lend support to the concept that the patchy atherosclerotic and arteriosclerotic lesions found in the coronary vessels of man may represent healed lesions of previous viral damage."}
{"id": "PMID:201265", "title": "Specific immunity in patients suffering from recurring warts before and after repetitive intradermal tests with human papilloma virus.", "content": "The specific humoral and cellular immunity of 22 patients with multiple or recurring warts was studied. After repeated intradermal tests, using an inactivated, purified viral antigen, the responses obtained could be classed into two groups. The first group (10 patients) was characterized immunologically by the acquisition of a specific cellular immunity and the appearance of circulating IgG antibodies, and clinically by a total regression of resolution of the warts two to three weeks after the final intradermal test. The second group (12 patients) was characterized immunologically by a weak or non-existent specific immune response, and clinically by the unmodified persistence of the warts.", "contents": "Specific immunity in patients suffering from recurring warts before and after repetitive intradermal tests with human papilloma virus. The specific humoral and cellular immunity of 22 patients with multiple or recurring warts was studied. After repeated intradermal tests, using an inactivated, purified viral antigen, the responses obtained could be classed into two groups. The first group (10 patients) was characterized immunologically by the acquisition of a specific cellular immunity and the appearance of circulating IgG antibodies, and clinically by a total regression of resolution of the warts two to three weeks after the final intradermal test. The second group (12 patients) was characterized immunologically by a weak or non-existent specific immune response, and clinically by the unmodified persistence of the warts."}
{"id": "PMID:201268", "title": "A biochemical explanation for the fatty liver and kidney syndrome of broilers: its alleviation by the short-term use of dietary fat.", "content": "1. Fatty livers and kidney syndrome (FLKS) was induced in young broiler chickens by giving them a diet composed principally of wheat and meat meal. 2. FLKS resulted in reduced growth and increased liver weight; fasting for 18 h increased mortality, liver lipid and the specific activity of hepatic ATP-citrate lyase compared with birds fed on a commercial diet. The specific activities of hepatic fructose-1,6-diphosphate-1-phosphohydrolase and pyruvate carboxylase were reduced in birds suffering from FLKS and fasted for 18 h. 3. Feeding of the FLKS-inducing diet supplemented with 150 g animal tallow/kg for 54 h considerably reduced mortality while restoring liver composition and enzyme activities towards those observed in birds fed a commercial diet. Investigations indicated that the glycerol component of the fat was not responsible for the observed responses. 4. The present results suggest that in FLKS insufficiencies of biotin are induced in specific enzyme systems, but the syndrome may be alleviated without the use of supplementary biotin. 5. The evidence indicates that, when stressed, birds affected by FLKS diet from the hypoglycaemia occurring as a result of a reduced capacity for gluconeogenesis.", "contents": "A biochemical explanation for the fatty liver and kidney syndrome of broilers: its alleviation by the short-term use of dietary fat. 1. Fatty livers and kidney syndrome (FLKS) was induced in young broiler chickens by giving them a diet composed principally of wheat and meat meal. 2. FLKS resulted in reduced growth and increased liver weight; fasting for 18 h increased mortality, liver lipid and the specific activity of hepatic ATP-citrate lyase compared with birds fed on a commercial diet. The specific activities of hepatic fructose-1,6-diphosphate-1-phosphohydrolase and pyruvate carboxylase were reduced in birds suffering from FLKS and fasted for 18 h. 3. Feeding of the FLKS-inducing diet supplemented with 150 g animal tallow/kg for 54 h considerably reduced mortality while restoring liver composition and enzyme activities towards those observed in birds fed a commercial diet. Investigations indicated that the glycerol component of the fat was not responsible for the observed responses. 4. The present results suggest that in FLKS insufficiencies of biotin are induced in specific enzyme systems, but the syndrome may be alleviated without the use of supplementary biotin. 5. The evidence indicates that, when stressed, birds affected by FLKS diet from the hypoglycaemia occurring as a result of a reduced capacity for gluconeogenesis."}
{"id": "PMID:201270", "title": "Maternal nutrition in early pregnancy.", "content": "1. Mean daily nutrient intakes of 195 women in the first trimester of pregnancy were assessed by weighed dietary records. 2. In comparsion with recommended intakes for non-pregnant women aged 18-55 years (Department of Health and Social Security, 1969), more than two-thirds of the subjects were having insufficient energy, iron and cholecalciferol. Unsatisfactory intakes of other nutrients were not uncommon. In relation to recommended intakes for the second trimester (Department of Health and Social Security, 1969), all mothers were having insufficient cholecalciferol and more than 80% of mothers had unsatisfactory intakes of energy and Fe. 3. Intakes appreciably lower than those recommended were associated with the following factors: social classes III, IV and V; maternal age under 20 years; smoking ten or more cigarettes daily; vomiting on more than 3 d/week.", "contents": "Maternal nutrition in early pregnancy. 1. Mean daily nutrient intakes of 195 women in the first trimester of pregnancy were assessed by weighed dietary records. 2. In comparsion with recommended intakes for non-pregnant women aged 18-55 years (Department of Health and Social Security, 1969), more than two-thirds of the subjects were having insufficient energy, iron and cholecalciferol. Unsatisfactory intakes of other nutrients were not uncommon. In relation to recommended intakes for the second trimester (Department of Health and Social Security, 1969), all mothers were having insufficient cholecalciferol and more than 80% of mothers had unsatisfactory intakes of energy and Fe. 3. Intakes appreciably lower than those recommended were associated with the following factors: social classes III, IV and V; maternal age under 20 years; smoking ten or more cigarettes daily; vomiting on more than 3 d/week."}
{"id": "PMID:201275", "title": "Nuclear magnetic resonance studies of lipid-protein interactions. A model of the dynamics and energetics of phosphatidylcholine bilayers that contain cytochrome c oxidase.", "content": "Reconstituted membrane systems of synthetic phosphatidylcholines and the integral membrane enzyme cytochrome c oxidase were prepared in order to conduct nuclear magnetic resonance studies of lipid-protein interactions. These lipids, labeled with a geminate difluoro group on the 1-position hydrocarbon chain, were combined with the enzyme to give active lipid-protein particles with a well-defined ratio of lipid to protein. The fluorine magnetic resonance spectra of a series of preparations with different lipid/protein ratios suggest that the hydrocarbon chain mobility of the lipid is substantially reduced with increasing amounts of protein. The fluorine spectra of a single lipid-protein preparation show a dramatic increase in the number of the more mobile lipid chains with increasing temperature. The results suggest that the enzyme orders the lipid bilayer well beyond those lipids in direct contact with the protein surface, and that the amount of the lipid restricted by the enzyme is dependent upon temperature. The exchange of lipid between the restricted and the more mobile lipid environments most probably does not occur over the time scale measurable by the magnetic resonance techniques, about 10(-3) s.", "contents": "Nuclear magnetic resonance studies of lipid-protein interactions. A model of the dynamics and energetics of phosphatidylcholine bilayers that contain cytochrome c oxidase. Reconstituted membrane systems of synthetic phosphatidylcholines and the integral membrane enzyme cytochrome c oxidase were prepared in order to conduct nuclear magnetic resonance studies of lipid-protein interactions. These lipids, labeled with a geminate difluoro group on the 1-position hydrocarbon chain, were combined with the enzyme to give active lipid-protein particles with a well-defined ratio of lipid to protein. The fluorine magnetic resonance spectra of a series of preparations with different lipid/protein ratios suggest that the hydrocarbon chain mobility of the lipid is substantially reduced with increasing amounts of protein. The fluorine spectra of a single lipid-protein preparation show a dramatic increase in the number of the more mobile lipid chains with increasing temperature. The results suggest that the enzyme orders the lipid bilayer well beyond those lipids in direct contact with the protein surface, and that the amount of the lipid restricted by the enzyme is dependent upon temperature. The exchange of lipid between the restricted and the more mobile lipid environments most probably does not occur over the time scale measurable by the magnetic resonance techniques, about 10(-3) s."}
{"id": "PMID:201276", "title": "Lipid requirements for cytochrome c oxidase activity.", "content": "Cytochrome c oxidase depleted of endogenous lipid by detergent exchange has been reconstituted into vesicles with synthetic lipids of known head group and fatty acid composition and enzymic activities have been measured. No evidence for head group specificity was found. However, the enzyme does require the fluid environment provided by unsaturated fatty acids. The state of dispersion of the enzyme was found to affect the activities regenerated in reconstitution studies. The highest activities were obtained using lysolecithin containing an oleoyl fatty acid as the lipid component.", "contents": "Lipid requirements for cytochrome c oxidase activity. Cytochrome c oxidase depleted of endogenous lipid by detergent exchange has been reconstituted into vesicles with synthetic lipids of known head group and fatty acid composition and enzymic activities have been measured. No evidence for head group specificity was found. However, the enzyme does require the fluid environment provided by unsaturated fatty acids. The state of dispersion of the enzyme was found to affect the activities regenerated in reconstitution studies. The highest activities were obtained using lysolecithin containing an oleoyl fatty acid as the lipid component."}
{"id": "PMID:201277", "title": "In vivo inhibition of Novikoff cytoplasmic messenger RNA methylation by S-tubercidinylhomocysteine.", "content": "The analogue S-tubercidinylhomocysteine (STH) has been used to study the methylation of mRNA in vivo. Partial inhibition of cytoplasmic poly(A)-RNA methylation was observed using a level of inhibitor which still permitted cell growth. Characterization of the partially methylated mRNA indicated the presence of cap structures lacking 2'-O-methylnucleosides, m7GpppN', which are normally not found in mammalian mRNA. Inhibition of additional methylated sites in mRNA at the second 2'-O-methynucleoside, and at internal N6-methyladenosine was also observed Methylation of 7-methylguanosine was not affected under the conditions used in these experiments. The methylnucleoside composition of cap structures differed in STH-inhibited and uninhibited cells. These results indicate that a completely methylated cap is not required for transport of mRNA into the cytoplasm. Furthermore, it may now be possible to assess in vivo the sequential nature of mRNA methylation and its potential role in mRNA processing.", "contents": "In vivo inhibition of Novikoff cytoplasmic messenger RNA methylation by S-tubercidinylhomocysteine. The analogue S-tubercidinylhomocysteine (STH) has been used to study the methylation of mRNA in vivo. Partial inhibition of cytoplasmic poly(A)-RNA methylation was observed using a level of inhibitor which still permitted cell growth. Characterization of the partially methylated mRNA indicated the presence of cap structures lacking 2'-O-methylnucleosides, m7GpppN', which are normally not found in mammalian mRNA. Inhibition of additional methylated sites in mRNA at the second 2'-O-methynucleoside, and at internal N6-methyladenosine was also observed Methylation of 7-methylguanosine was not affected under the conditions used in these experiments. The methylnucleoside composition of cap structures differed in STH-inhibited and uninhibited cells. These results indicate that a completely methylated cap is not required for transport of mRNA into the cytoplasm. Furthermore, it may now be possible to assess in vivo the sequential nature of mRNA methylation and its potential role in mRNA processing."}
{"id": "PMID:201278", "title": "Changes in the plasma lipoprotein-apoproteins of guinea pigs in response to dietary cholesterol.", "content": "The major apoproteins from four plasma lipoproteins were isolated from control and cholesterol-fed guinea pigs. Apoproteins were studied by column chromatography, polyacrylamide gel electrophoresis, and amino acid analysis. Dietary cholesterol altered the plasma apolipoproteins mainly by an enrichment in the content of arginine-rich polypeptide (ARP) in all density fractions. This protein had a similar molecular weight (34 000), electrophoretic mobility, amino acid composition, and microheterogeneity as ARP reported in other mammalian species. The estimation of plasma concentration of ARP indicates a higher correlation coefficient with plasma unesterified cholesterol (r = 0.98) compared with cholesterol esters (r = 0.62).", "contents": "Changes in the plasma lipoprotein-apoproteins of guinea pigs in response to dietary cholesterol. The major apoproteins from four plasma lipoproteins were isolated from control and cholesterol-fed guinea pigs. Apoproteins were studied by column chromatography, polyacrylamide gel electrophoresis, and amino acid analysis. Dietary cholesterol altered the plasma apolipoproteins mainly by an enrichment in the content of arginine-rich polypeptide (ARP) in all density fractions. This protein had a similar molecular weight (34 000), electrophoretic mobility, amino acid composition, and microheterogeneity as ARP reported in other mammalian species. The estimation of plasma concentration of ARP indicates a higher correlation coefficient with plasma unesterified cholesterol (r = 0.98) compared with cholesterol esters (r = 0.62)."}
{"id": "PMID:201279", "title": "Neurotoxins of Bungarus multicinctus vernom. Purification and partial characterization.", "content": "The purification to homogeneity of nine neurotoxic components of the venom of Bungarus multicinctus is described. The purified components include alpha-bungarotoxin and two other alpha-type synaptic toxins and beta-bungarotoxin and five other beta-type synaptic toxins. The purified toxins have been characterized by electrophoresis, isoelectric focusing, amino acid analysis, and N-terminal amino acid determination. The alpha-type synaptic neurotoxins constitute a discrete class with molecular weights of 7000-8500, isoelectric points (pI) of 9.0-9.2, and N-terminal isoleucine or methionine. The beta-type synaptic neurotoxins constitute a second group with molecular weights of 20 000-22 000 and pI = 8.8-9.7. Fractions 10 through 13 exhibit a chain structure consisting of a 6000-7000 light chain and a 11 000-15 000 heavy chain apparently covalently stabilized by interchain disulfides. Fractions 9A and 14 were single chains of 11 000-14 000 which resemble the sequenced beta-type synaptic neurotoxin notexin (Halpert, J., and Eaker, D. (1975), J. Biol. Chem. 250, 6990). All of the beta-type synaptic toxins have a single tryptophan and N-terminal aspartic acid or asparagine.", "contents": "Neurotoxins of Bungarus multicinctus vernom. Purification and partial characterization. The purification to homogeneity of nine neurotoxic components of the venom of Bungarus multicinctus is described. The purified components include alpha-bungarotoxin and two other alpha-type synaptic toxins and beta-bungarotoxin and five other beta-type synaptic toxins. The purified toxins have been characterized by electrophoresis, isoelectric focusing, amino acid analysis, and N-terminal amino acid determination. The alpha-type synaptic neurotoxins constitute a discrete class with molecular weights of 7000-8500, isoelectric points (pI) of 9.0-9.2, and N-terminal isoleucine or methionine. The beta-type synaptic neurotoxins constitute a second group with molecular weights of 20 000-22 000 and pI = 8.8-9.7. Fractions 10 through 13 exhibit a chain structure consisting of a 6000-7000 light chain and a 11 000-15 000 heavy chain apparently covalently stabilized by interchain disulfides. Fractions 9A and 14 were single chains of 11 000-14 000 which resemble the sequenced beta-type synaptic neurotoxin notexin (Halpert, J., and Eaker, D. (1975), J. Biol. Chem. 250, 6990). All of the beta-type synaptic toxins have a single tryptophan and N-terminal aspartic acid or asparagine."}
{"id": "PMID:201280", "title": "Purification of cyclic 3',5'-nucleotide phosphodiesterase inhibitory protein by affinity chromatography on activator protein coupled to Sepharose.", "content": "The Ca2+-dependent, reversible, interaction of cyclic adenosine 3',5'-monophosphate (cAMP) phosphodiesterase with its activator has been used to purify the enzyme by affinity chromatography. Activator-dependent cAMP phosphodiesterase is only a minor component of the proteins specifically adsorbed in the presence of Ca2+ by the Ca2+-dependent activator protein coupled to Sepharose and subsequently released by [ethylenebis(oxyethylenenitrilo)]tetraacetic acid. The major protein component can be partially resolved from the enzyme by gel filtration on Sephadex G-200. This protein has been purified to apparent homogeneity and shown to be composed of two polypeptide chains with molecular weights of 61,000 and 15,000 respectively. This protein is, by itself, devoid of phosphodiesterase activity and inhibits the activation of cAMP phosphodiesterase by its activator without affecting the basal activity. Thus, activation of cAMP phosphodiesteriase by the Ca2+-dependent activator protein may be controlled by interactions with yet a third component of the enzyme complex.", "contents": "Purification of cyclic 3',5'-nucleotide phosphodiesterase inhibitory protein by affinity chromatography on activator protein coupled to Sepharose. The Ca2+-dependent, reversible, interaction of cyclic adenosine 3',5'-monophosphate (cAMP) phosphodiesterase with its activator has been used to purify the enzyme by affinity chromatography. Activator-dependent cAMP phosphodiesterase is only a minor component of the proteins specifically adsorbed in the presence of Ca2+ by the Ca2+-dependent activator protein coupled to Sepharose and subsequently released by [ethylenebis(oxyethylenenitrilo)]tetraacetic acid. The major protein component can be partially resolved from the enzyme by gel filtration on Sephadex G-200. This protein has been purified to apparent homogeneity and shown to be composed of two polypeptide chains with molecular weights of 61,000 and 15,000 respectively. This protein is, by itself, devoid of phosphodiesterase activity and inhibits the activation of cAMP phosphodiesterase by its activator without affecting the basal activity. Thus, activation of cAMP phosphodiesteriase by the Ca2+-dependent activator protein may be controlled by interactions with yet a third component of the enzyme complex."}
{"id": "PMID:201281", "title": "Altering the specificity of restriction endonuclease: effect of replacing Mg2+ with Mn2+.", "content": "In the presence of 100 mM Tris buffer (pH 7.5) and 1-10 mM Mg2+ EcoRI endonuclease cleaves DNA at a specific nucleotide sequence and in a characteristic way: -GAATTC-. But if Mg2+ is replaced by Mn2+, the specificity of the cleavage is relaxed and cleavages occur at many other sites; moreover, there appears to be a hierarchy of cleavage rates at the pseudo-EcoRI restriction sites. For example, SV40 DNA is cleaved only once in the usual digestion conditions, but with Mn2+ more than ten cleavages are made; the five most rapidly cleaved SV40 DNA map locations are 0/1.0 larger than 0.93 larger than 0.33 approximately equal to 0.42 larger than 0.29 approximately equal to 0.40 larger than 0.25. Mn2+ also alters the restriction specificity of HindIII but not HpaII endonuclease.", "contents": "Altering the specificity of restriction endonuclease: effect of replacing Mg2+ with Mn2+. In the presence of 100 mM Tris buffer (pH 7.5) and 1-10 mM Mg2+ EcoRI endonuclease cleaves DNA at a specific nucleotide sequence and in a characteristic way: -GAATTC-. But if Mg2+ is replaced by Mn2+, the specificity of the cleavage is relaxed and cleavages occur at many other sites; moreover, there appears to be a hierarchy of cleavage rates at the pseudo-EcoRI restriction sites. For example, SV40 DNA is cleaved only once in the usual digestion conditions, but with Mn2+ more than ten cleavages are made; the five most rapidly cleaved SV40 DNA map locations are 0/1.0 larger than 0.93 larger than 0.33 approximately equal to 0.42 larger than 0.29 approximately equal to 0.40 larger than 0.25. Mn2+ also alters the restriction specificity of HindIII but not HpaII endonuclease."}
{"id": "PMID:201282", "title": "Sedimentation behavior of native and reduced apolipoprotein A-II from human high density lipoproteins.", "content": "The solution properties of human serum apolipoprotein A-II, both in the native and in the reduced forms, were investigated by the technique of sedimentation equilibrium in the analytical ultracentrifuge. For both proteins, the apparent weight average molecular weights determined in neutral buffer systems were found to be dependent on protein concentration and invariant with the rotor speeds used (16,000 to 44,000 rpm) indicating a reversible self-association. These results were also found to be independent of temperature between 5 and 30 degrees C. The pattern of self-association of native apolipoprotein A-II could best be described by a monomer-dimer-trimer equilibrium, in agreement with previously reported data (Vitello, L B., and Scanu, A. M. (1975), Biochemistry 15, 1161). The self-association pattern of apolipoprotein A-II reduced in the presence of 50 mM dithiothreitol conformed with a monomer-dimer-tetramer equilibrium similar to that reported for the native single chain apolipoprotein A-II of the rhesus monkey (Barbeau, D. L., et al. (1977), J. Biol. Chem. 252, 6745), but differing significantly from that reported for the reduced and carboxymethylated human product (Osborne, J. C. , et al. (1975), Biochemistry 14, 3741).", "contents": "Sedimentation behavior of native and reduced apolipoprotein A-II from human high density lipoproteins. The solution properties of human serum apolipoprotein A-II, both in the native and in the reduced forms, were investigated by the technique of sedimentation equilibrium in the analytical ultracentrifuge. For both proteins, the apparent weight average molecular weights determined in neutral buffer systems were found to be dependent on protein concentration and invariant with the rotor speeds used (16,000 to 44,000 rpm) indicating a reversible self-association. These results were also found to be independent of temperature between 5 and 30 degrees C. The pattern of self-association of native apolipoprotein A-II could best be described by a monomer-dimer-trimer equilibrium, in agreement with previously reported data (Vitello, L B., and Scanu, A. M. (1975), Biochemistry 15, 1161). The self-association pattern of apolipoprotein A-II reduced in the presence of 50 mM dithiothreitol conformed with a monomer-dimer-tetramer equilibrium similar to that reported for the native single chain apolipoprotein A-II of the rhesus monkey (Barbeau, D. L., et al. (1977), J. Biol. Chem. 252, 6745), but differing significantly from that reported for the reduced and carboxymethylated human product (Osborne, J. C. , et al. (1975), Biochemistry 14, 3741)."}
{"id": "PMID:201283", "title": "Estimation of transmembrane potentials from phase equilibria of hydrophobic paramagnetic ions.", "content": "Positively charged hydrophobic spin labels have been synthesized which respond to transmembrane potentials in sonicated liposomes. Electron paramagnetic resonance spectroscopy is used to show that the distribution of these probes between aqueous and membrane phases changes as a function of transmembrane potential. When liposomes are made more inside-negative, the fraction of membrane associated probe increases while the fraction of probe in the aqueous phase decreases. The results are in quantitative agreement with a simple equilibrium thermodynamic theory which allows estimation of absolute transmembrane potentials in phospholipid vesicles.", "contents": "Estimation of transmembrane potentials from phase equilibria of hydrophobic paramagnetic ions. Positively charged hydrophobic spin labels have been synthesized which respond to transmembrane potentials in sonicated liposomes. Electron paramagnetic resonance spectroscopy is used to show that the distribution of these probes between aqueous and membrane phases changes as a function of transmembrane potential. When liposomes are made more inside-negative, the fraction of membrane associated probe increases while the fraction of probe in the aqueous phase decreases. The results are in quantitative agreement with a simple equilibrium thermodynamic theory which allows estimation of absolute transmembrane potentials in phospholipid vesicles."}
{"id": "PMID:201284", "title": "Analysis of rat repetitive DNA sequences.", "content": "Parameters of repetitive sequence organization have been measured in the rat genome. Experiments using melting, hydroxylapatite binding, and single strand specific nuclease digestion have been used to measure the number, length, and arrangement of repeated DNA sequences. Renaturation and melting or S1 nuclease digestion of 1.0 kbp DNA fragment show about 20% of rat DNA sequences are 3000-fold repeated. Renatured duplexes from 4.0 kbp DNA fragments display two repetitive size fractions after nuclease digestion. About 60% of the repeated sequences are 0.2-0.4 kbp long while the remainder are longer than 1.5 kbp. The arrangement of the repeated sequences has been measured by hydroxylapatite fractionation of DNA fragments of varying lengths bearing a repeated sequence. Repeated DNA sequences are interspersed among 2.5 kbp long nonrepeated sequences throughout more than 70% of the rat genome. There are approximately 350 different 3000-fold short repeated sequences in the rat interspersed among 600,000 nonrepeated DNA sequences.", "contents": "Analysis of rat repetitive DNA sequences. Parameters of repetitive sequence organization have been measured in the rat genome. Experiments using melting, hydroxylapatite binding, and single strand specific nuclease digestion have been used to measure the number, length, and arrangement of repeated DNA sequences. Renaturation and melting or S1 nuclease digestion of 1.0 kbp DNA fragment show about 20% of rat DNA sequences are 3000-fold repeated. Renatured duplexes from 4.0 kbp DNA fragments display two repetitive size fractions after nuclease digestion. About 60% of the repeated sequences are 0.2-0.4 kbp long while the remainder are longer than 1.5 kbp. The arrangement of the repeated sequences has been measured by hydroxylapatite fractionation of DNA fragments of varying lengths bearing a repeated sequence. Repeated DNA sequences are interspersed among 2.5 kbp long nonrepeated sequences throughout more than 70% of the rat genome. There are approximately 350 different 3000-fold short repeated sequences in the rat interspersed among 600,000 nonrepeated DNA sequences."}
{"id": "PMID:201285", "title": "Sequence organization of the rat genome by electron microscopy.", "content": "The size and arrangement of repetitive and inverted repeat (foldback) sequences in rat DNA were studied by visualization of hybrid and heteroduplex structures in the electron microscope. The self-reassociation of repetitive sequence-bearing DNA strands often results in the formation of four-ended \"H\" structures, whose duplex regions equal the repetitive sequence length and can be measured in the electron microscope. In this way, it was determined that the average size of the class of numerous short repetitive sequences is 0.40 +/- 0.15 kbp. Heteroduplex structures were prepared between long whole DNA single strands and short repeat-sequence-bearing strands. The analysis of these structures confirms that the size of the repetitive sequences in 0.4 kbp on average. Length measurements between adjacent duplexes show that the average spacing between two interspersed repeats is at least 1.5-1.8 kbp. By examining 29.4-kbp single strands after brief renaturation, the size and distribution of foldback sequences were determined. There are 1.9 X 10(5) foldback apirs per rat genome, spaced an average of 9.7 kbp apart according to our measurement. Repetitive, inverted repeat and unique sequences are interspersed with each other in at least half the genome.", "contents": "Sequence organization of the rat genome by electron microscopy. The size and arrangement of repetitive and inverted repeat (foldback) sequences in rat DNA were studied by visualization of hybrid and heteroduplex structures in the electron microscope. The self-reassociation of repetitive sequence-bearing DNA strands often results in the formation of four-ended \"H\" structures, whose duplex regions equal the repetitive sequence length and can be measured in the electron microscope. In this way, it was determined that the average size of the class of numerous short repetitive sequences is 0.40 +/- 0.15 kbp. Heteroduplex structures were prepared between long whole DNA single strands and short repeat-sequence-bearing strands. The analysis of these structures confirms that the size of the repetitive sequences in 0.4 kbp on average. Length measurements between adjacent duplexes show that the average spacing between two interspersed repeats is at least 1.5-1.8 kbp. By examining 29.4-kbp single strands after brief renaturation, the size and distribution of foldback sequences were determined. There are 1.9 X 10(5) foldback apirs per rat genome, spaced an average of 9.7 kbp apart according to our measurement. Repetitive, inverted repeat and unique sequences are interspersed with each other in at least half the genome."}
{"id": "PMID:201286", "title": "The mechanism of energy conservation and transduction by mitochondrial cytochrome c oxidase.", "content": "Oxidation of ferrocytochrome c by molecular oxygen catalysed by cytochrome c oxidase (cytochrome aa3) is coupled to translocation of H+ ions across the mitochondrial membrane. The proton pump is an intrinsic property of the cytochrome c oxidase complex as revealed by studies with phospholipid vesicles inlayed with the purified enzyme. As the conformation of cytochrome aa3 is specifically sensitive to the electrochemical proton gradient across the mitochondrial membrane, it is likely that redox energy is primarily conserved as a conformational \"strain\" in the cytochrome aa3 complex, followed by relaxation linked to proton translocation. Similar principles of energy conservation and transduction may apply on other respiratory chain complexes and on mitochondrial ATP synthase.", "contents": "The mechanism of energy conservation and transduction by mitochondrial cytochrome c oxidase. Oxidation of ferrocytochrome c by molecular oxygen catalysed by cytochrome c oxidase (cytochrome aa3) is coupled to translocation of H+ ions across the mitochondrial membrane. The proton pump is an intrinsic property of the cytochrome c oxidase complex as revealed by studies with phospholipid vesicles inlayed with the purified enzyme. As the conformation of cytochrome aa3 is specifically sensitive to the electrochemical proton gradient across the mitochondrial membrane, it is likely that redox energy is primarily conserved as a conformational \"strain\" in the cytochrome aa3 complex, followed by relaxation linked to proton translocation. Similar principles of energy conservation and transduction may apply on other respiratory chain complexes and on mitochondrial ATP synthase."}
{"id": "PMID:201287", "title": "Effects of deoxycholate and phospholipase A2 on choline and ethanolamine phosphotransferases of chicken brain microsomes.", "content": "Ethanolamine phosphotransferase (EC 2.7.8.1) and choline phosphotransferase (EC 2.7.8.2) activities were assayed in fresh microsomes from adult chicken brains with either diacylglycerols or alkylacylglycerols. Pretreatment of microsomes with 1.25 mM sodium deoxycholate, a concentration less than the critical micelle concentration, produced a slight inhibition of choline phosphotransferase activity. A deoxycholate concentration (5.0 mM) greater than the critical micelle concentration (3.0 mM) decreased the choline phosphotransferase activity by more than 70% but had no effect on ethanolamine phosphotransferase activity. Inclusion of 1.25 mM deoxycholate in the assay medium decreased choline phosphotransferase activity 35% but increased ethanolamine phosphotransferase activity 50%. The deoxycholate appeared to inactive the choline phosphotransferase. Phospholipase A2 (Vipera russelli) treatments of microsomes removed phosphoglycerides and decreased both phosphotransferase activities to a similar extent. Decreased activities are probably due to disruption of the membrane structure. Choline and ethanolamine phosphotransferase activities are apparently in different enzymes which lack specificity for the type of diglyceride. Thus, the systematic names should include 1,2-diradyl-sn-glycerol instead of 1,2-diacyl-sn-glycerol.", "contents": "Effects of deoxycholate and phospholipase A2 on choline and ethanolamine phosphotransferases of chicken brain microsomes. Ethanolamine phosphotransferase (EC 2.7.8.1) and choline phosphotransferase (EC 2.7.8.2) activities were assayed in fresh microsomes from adult chicken brains with either diacylglycerols or alkylacylglycerols. Pretreatment of microsomes with 1.25 mM sodium deoxycholate, a concentration less than the critical micelle concentration, produced a slight inhibition of choline phosphotransferase activity. A deoxycholate concentration (5.0 mM) greater than the critical micelle concentration (3.0 mM) decreased the choline phosphotransferase activity by more than 70% but had no effect on ethanolamine phosphotransferase activity. Inclusion of 1.25 mM deoxycholate in the assay medium decreased choline phosphotransferase activity 35% but increased ethanolamine phosphotransferase activity 50%. The deoxycholate appeared to inactive the choline phosphotransferase. Phospholipase A2 (Vipera russelli) treatments of microsomes removed phosphoglycerides and decreased both phosphotransferase activities to a similar extent. Decreased activities are probably due to disruption of the membrane structure. Choline and ethanolamine phosphotransferase activities are apparently in different enzymes which lack specificity for the type of diglyceride. Thus, the systematic names should include 1,2-diradyl-sn-glycerol instead of 1,2-diacyl-sn-glycerol."}
{"id": "PMID:201289", "title": "NAD-dependent 3alpha- and 12alpha-hydroxysteroid dehydrogenase activities from Eubacterium lentum ATCC no. 25559.", "content": "Eubacterium lentum (ATCC No. 25559) was shown to contain 3alpha-and 12alpha-hydroxysteroid dehydrogenases both of which were NAD-dependent and active against conjugated and unconjugated bile salts. In addition, the 3alpha-hydroxysteroid dehydrogenase was active against members of the Androstan series containing a 3alpha-hydroxyl group regardless of the stereo-orientation of the 5-H-. No measurable activity against 7alpha-, 7beta-, 11beta-, or 17beta-hydroxyl groups was demonstrated. The growth of E. lentum and the production of 3alpha- and 12alpha-hydroxysteroid dehydrogenases were greatly enhanced by the addition of L-, D- or DL-arginine to the medium. Yields of hydroxysteroid dehydrogenase were optimal in the range of 0.50-0.75% arginine; however, the growth of the organisms was further enhanced at arginine concentrations greater than 0.75%. The 12alpha-hydroxysteroid dehydrogenase was heat labile and could be selectively inactivated by heating at 50 degrees C for 45 min. Both the heated enzyme preparation (containing only 3alpha-hydroxysteroid dehydrogenase) and the unheated enzyme preparation (containing 3alpha- and 12alpha-hydroxysteroid dehydrogenases) were useful in the spectrophotometric quantification of bile salts. The optimal pH values for 3alpha- and 12alpha-hydroxysteroid dehydrogenases were 11.3 and 10.2, respectively. Kinetic studies have Km estimates of 2.10(-5) M and 1.0.10(-4) M with 3alpha,7alpha-dihydroxy-5beta-cholanoyl glycine and 7alpha,12alpha-dihydroxy-5beta-cholanoate for the two respective enzymes.", "contents": "NAD-dependent 3alpha- and 12alpha-hydroxysteroid dehydrogenase activities from Eubacterium lentum ATCC no. 25559. Eubacterium lentum (ATCC No. 25559) was shown to contain 3alpha-and 12alpha-hydroxysteroid dehydrogenases both of which were NAD-dependent and active against conjugated and unconjugated bile salts. In addition, the 3alpha-hydroxysteroid dehydrogenase was active against members of the Androstan series containing a 3alpha-hydroxyl group regardless of the stereo-orientation of the 5-H-. No measurable activity against 7alpha-, 7beta-, 11beta-, or 17beta-hydroxyl groups was demonstrated. The growth of E. lentum and the production of 3alpha- and 12alpha-hydroxysteroid dehydrogenases were greatly enhanced by the addition of L-, D- or DL-arginine to the medium. Yields of hydroxysteroid dehydrogenase were optimal in the range of 0.50-0.75% arginine; however, the growth of the organisms was further enhanced at arginine concentrations greater than 0.75%. The 12alpha-hydroxysteroid dehydrogenase was heat labile and could be selectively inactivated by heating at 50 degrees C for 45 min. Both the heated enzyme preparation (containing only 3alpha-hydroxysteroid dehydrogenase) and the unheated enzyme preparation (containing 3alpha- and 12alpha-hydroxysteroid dehydrogenases) were useful in the spectrophotometric quantification of bile salts. The optimal pH values for 3alpha- and 12alpha-hydroxysteroid dehydrogenases were 11.3 and 10.2, respectively. Kinetic studies have Km estimates of 2.10(-5) M and 1.0.10(-4) M with 3alpha,7alpha-dihydroxy-5beta-cholanoyl glycine and 7alpha,12alpha-dihydroxy-5beta-cholanoate for the two respective enzymes."}
{"id": "PMID:201290", "title": "The turnover of human plasma very low density lipoprotein protein.", "content": "The plasma decay of three groups of iodinated apoproteins on human very low density lipoproteins were evauluated in two normals, two subjects with endogenous hypertriglyceridemia and another two with dysbetalipoproteinemia. The apo beta decay was more rapid than that of the C apoproteins in all patients. The apo beta decay was more rapid for the normals than for either the subjects with hypertriglyceridemia or dysbetalipoprotenemia. The apo C protein had an irregular decay in the normals but decayed less irregularly for the hypertriglyceridemics. The arginine rich apoprotein had a decay somewhat similar to apo C protein in the normals. The apo beta protein of the alpha2 very low density lipoprotein of a dysbetalipoproteinemic was consistent with a precursor relationship to the apo beta of beta very low density lipoprotein of this subject, but the arginine rich apoprotein was not.", "contents": "The turnover of human plasma very low density lipoprotein protein. The plasma decay of three groups of iodinated apoproteins on human very low density lipoproteins were evauluated in two normals, two subjects with endogenous hypertriglyceridemia and another two with dysbetalipoproteinemia. The apo beta decay was more rapid than that of the C apoproteins in all patients. The apo beta decay was more rapid for the normals than for either the subjects with hypertriglyceridemia or dysbetalipoprotenemia. The apo C protein had an irregular decay in the normals but decayed less irregularly for the hypertriglyceridemics. The arginine rich apoprotein had a decay somewhat similar to apo C protein in the normals. The apo beta protein of the alpha2 very low density lipoprotein of a dysbetalipoproteinemic was consistent with a precursor relationship to the apo beta of beta very low density lipoprotein of this subject, but the arginine rich apoprotein was not."}
{"id": "PMID:201291", "title": "Subunit structure of the reconstitutively active cytochrome b-c1 complex. Determination of amino acids and molar distribution of subunit fractions from gel electrophoresis.", "content": "A quantitative method has been developed to analyze the amino acid composition of protein subunits directly from the Coomassie Blue-stained band of polyacrylamide gel columns after electrophoresis. It is an improved method originally reported by Houston (Houston, L. L. (1971) Anal. Biochem. 44, 81--88). The results obtained can be thus used for the calculation of the molar ratios of subunit components of protein. The manipulation of the method and computation of the results are illustrated by a very complicated lipoprotein complex. The subunit molar ratios of the reconstitutively active cytochrome b-c1 complex were determined to be 2, 2, 2, 3, 2, 2, and 5 among the seven bands of the corresponding molecular weights of 53 000, 50 000, 37 000, 30 000, 28 000, 17 000, and 15 000, from gel electrophoretic columns. The amino acid composition of each subunit fraction determined directly from hydrolysis of gel was comparable with that obtained by actual isolation of each subunit.", "contents": "Subunit structure of the reconstitutively active cytochrome b-c1 complex. Determination of amino acids and molar distribution of subunit fractions from gel electrophoresis. A quantitative method has been developed to analyze the amino acid composition of protein subunits directly from the Coomassie Blue-stained band of polyacrylamide gel columns after electrophoresis. It is an improved method originally reported by Houston (Houston, L. L. (1971) Anal. Biochem. 44, 81--88). The results obtained can be thus used for the calculation of the molar ratios of subunit components of protein. The manipulation of the method and computation of the results are illustrated by a very complicated lipoprotein complex. The subunit molar ratios of the reconstitutively active cytochrome b-c1 complex were determined to be 2, 2, 2, 3, 2, 2, and 5 among the seven bands of the corresponding molecular weights of 53 000, 50 000, 37 000, 30 000, 28 000, 17 000, and 15 000, from gel electrophoretic columns. The amino acid composition of each subunit fraction determined directly from hydrolysis of gel was comparable with that obtained by actual isolation of each subunit."}
{"id": "PMID:201292", "title": "Identification of subunits of bovine heart cytochrome oxidase.", "content": "Purified lipid-depleted cytochrome oxidase, at purity of 12--14 nmol heme a per mg protein, has been shown to contain seven non-identical subunits in the ratio of unity. Their molucular weights on polyacrylamide gel are, in thousands, 40, 21, 14.8, 13.5, 11.6, 9.5, and 7.6 from gel electrophoresis after dissociation in sodium dodecyl sulfate and beta-mercaptoethanol. The molar ratio is determined by the amino acid composition of each subunit obtained from direct hydrolysis of the stained polyacrylamide gel slices. The amino acid composition of the isolated subunits I and II determined by regular hydrolysis method is found practically the same as that from direct hydrolysis of gel slices. The heme-associated polypeptides are identified with subunits of molecular weights of 40.10(3) and 11.6.10(3). One of the two coppers associated with the polypeptide of molecular weight of 21 000. The second copper may be associated with heme in the subunit of 40.10(3). Evidence of the existence of interpolypeptide disulfide linkages is presented.", "contents": "Identification of subunits of bovine heart cytochrome oxidase. Purified lipid-depleted cytochrome oxidase, at purity of 12--14 nmol heme a per mg protein, has been shown to contain seven non-identical subunits in the ratio of unity. Their molucular weights on polyacrylamide gel are, in thousands, 40, 21, 14.8, 13.5, 11.6, 9.5, and 7.6 from gel electrophoresis after dissociation in sodium dodecyl sulfate and beta-mercaptoethanol. The molar ratio is determined by the amino acid composition of each subunit obtained from direct hydrolysis of the stained polyacrylamide gel slices. The amino acid composition of the isolated subunits I and II determined by regular hydrolysis method is found practically the same as that from direct hydrolysis of gel slices. The heme-associated polypeptides are identified with subunits of molecular weights of 40.10(3) and 11.6.10(3). One of the two coppers associated with the polypeptide of molecular weight of 21 000. The second copper may be associated with heme in the subunit of 40.10(3). Evidence of the existence of interpolypeptide disulfide linkages is presented."}
{"id": "PMID:201293", "title": "Determination of calcium transport and phosphoprotein phosphatase activity in microsomes from respiratory and vascular smooth muscle.", "content": "1. Calcium transport into microsomal vesicles of respiratory (tracheal) smooth muscle was characterized. This calcium transport was ATP dependent and stimulated by the presence of the oxalate ion. The magnitude of transport was similar to that reported for microsomes from other types of smooth muscle. 2. Bovine and rabbit, heavy and light microsomes were isolated from respiratory (tracheal) and vascular (aortic) smooth muscle. Preincubation of these vesicles with cyclic AMP and protein kinase did not alter the transport of calcium into the vesicles. There uas no evidence of phosphate incorporation into microsomal membrane proteins. Similar results were obtained if phosphorylase b kinase replaced the combination of cyclic AMP and protein kinase during the preincubation. 3. The phosphoprotein phosphatase activity of cardiac sarcoplasmic reticulum and smooth muscle microsomes was determined. The activity of this enzyme was found to be several-fold less in the cardiac sarcoplasmic reticulum than in various smooth muscle microsome preparations.", "contents": "Determination of calcium transport and phosphoprotein phosphatase activity in microsomes from respiratory and vascular smooth muscle. 1. Calcium transport into microsomal vesicles of respiratory (tracheal) smooth muscle was characterized. This calcium transport was ATP dependent and stimulated by the presence of the oxalate ion. The magnitude of transport was similar to that reported for microsomes from other types of smooth muscle. 2. Bovine and rabbit, heavy and light microsomes were isolated from respiratory (tracheal) and vascular (aortic) smooth muscle. Preincubation of these vesicles with cyclic AMP and protein kinase did not alter the transport of calcium into the vesicles. There uas no evidence of phosphate incorporation into microsomal membrane proteins. Similar results were obtained if phosphorylase b kinase replaced the combination of cyclic AMP and protein kinase during the preincubation. 3. The phosphoprotein phosphatase activity of cardiac sarcoplasmic reticulum and smooth muscle microsomes was determined. The activity of this enzyme was found to be several-fold less in the cardiac sarcoplasmic reticulum than in various smooth muscle microsome preparations."}
{"id": "PMID:201296", "title": "Hemosiderin. an EPR study of water-insoluble iron in human and rat liver.", "content": "EPR spectra of the water-insoluble iron fraction, hemosiderin of human and rat liver are described. The homogenate of freshly prepared perfused rat liver shows a non-heme iron signal at g=4.3 and a high-spin heme-iron signal around g=6, whereas the washed and sonicated sample of the insoluble iron fraction shows solely a non-heme iron signal at g=4.3. This indicates that hemosiderin from rat liver does not contain heme iron. Human-liver preparations from post mortem obtained material show in the homogenates as well as in the washed and sonicated samples an intense high-spin heme iron signal at g=6.0 and a non-heme iron signal at g=4.3. A comparative experiment, carried out with \"aged\" rat liver preparations, reveals the same spectra as with the human preparations. It is concluded that that the heme present in the insoluble iron fraction is caused by degradation of hemoglobin in the obduction material, and that heme is not a constituent of the insoluble depot iron.", "contents": "Hemosiderin. an EPR study of water-insoluble iron in human and rat liver. EPR spectra of the water-insoluble iron fraction, hemosiderin of human and rat liver are described. The homogenate of freshly prepared perfused rat liver shows a non-heme iron signal at g=4.3 and a high-spin heme-iron signal around g=6, whereas the washed and sonicated sample of the insoluble iron fraction shows solely a non-heme iron signal at g=4.3. This indicates that hemosiderin from rat liver does not contain heme iron. Human-liver preparations from post mortem obtained material show in the homogenates as well as in the washed and sonicated samples an intense high-spin heme iron signal at g=6.0 and a non-heme iron signal at g=4.3. A comparative experiment, carried out with \"aged\" rat liver preparations, reveals the same spectra as with the human preparations. It is concluded that that the heme present in the insoluble iron fraction is caused by degradation of hemoglobin in the obduction material, and that heme is not a constituent of the insoluble depot iron."}
{"id": "PMID:201299", "title": "Modified cyclic nucleotide systems in Morris hepatoma 3924A favoring expression of cyclic GMP effect.", "content": "Modifications in the cyclic nucleotide systems favoring the expression of cyclic GMP effects were found to occur in the transplanted fast-growing Morris hepatoma 3924A. These included: (a) a decreased level of cyclic GMP phosphodiesterase and an increased level of cyclic AMP phosphodiesterase; (b) a disproportionately increased level of cylic GMP-dependent protein kinase relative to that of cyclic AMP-dependent protein kinase; (c) a disproportionately increased level of stimulatory modulator of cyclic AMP-dependent protein kinase relative to that of inhibitory modulator of cyclic AMP-dependent protein kinase; and (d) an increased level of phosphoprotein phosphatase.", "contents": "Modified cyclic nucleotide systems in Morris hepatoma 3924A favoring expression of cyclic GMP effect. Modifications in the cyclic nucleotide systems favoring the expression of cyclic GMP effects were found to occur in the transplanted fast-growing Morris hepatoma 3924A. These included: (a) a decreased level of cyclic GMP phosphodiesterase and an increased level of cyclic AMP phosphodiesterase; (b) a disproportionately increased level of cylic GMP-dependent protein kinase relative to that of cyclic AMP-dependent protein kinase; (c) a disproportionately increased level of stimulatory modulator of cyclic AMP-dependent protein kinase relative to that of inhibitory modulator of cyclic AMP-dependent protein kinase; and (d) an increased level of phosphoprotein phosphatase."}
{"id": "PMID:201300", "title": "Lysis of halophilic Vibrio alginolyticus and Vibrio costicolus induced by chaotropic anions.", "content": "High concentration (1.0 M) of KSCN, but not of NaSCN, induced lysis of slightly halophilic Vibrio alginolyticus and moderately halophilic Vibrio costicolus, and the decrease in absorbance of the cell suspension was complete after 30 min at 25 degrees C. Replacement of K+ with Na+ effectively prevented the lysis by SCN-.K+ salts of NO3-, Br- and I-, however, induced no significant lysis. In electron micrographs, a prolonged exposure of the cells of V. alginolyticus to 1.0 M KSCN displaced the nucleoplasm to maintain close contact with the cell membranes. After 40 min of interaction, 50% of the cellular protein, 96% of RNA and 94% of DNA were recovered in the lysed cells. In contrast to lysis in hypotonic conditions, the lysis induced by KSCN is due mainly to a partial release of protein from the cells. V. costicolus  was more susceptible to SCN- than V. alginolyticus, whereas nonhalophilic Escherichia coli was resistant to 1.0 M KSCN. Thus, lysis by SCN- is characteristic of halophilic bacteria and cell membranes of more halophilic bacteria are more susceptible to chaotropic anions. The protective effect of Na+ observed here was considered to be manifested by specific interactions of Na+ with components of cell membranes, thereby rendering their structures resistant to the action of chaotropic anions.", "contents": "Lysis of halophilic Vibrio alginolyticus and Vibrio costicolus induced by chaotropic anions. High concentration (1.0 M) of KSCN, but not of NaSCN, induced lysis of slightly halophilic Vibrio alginolyticus and moderately halophilic Vibrio costicolus, and the decrease in absorbance of the cell suspension was complete after 30 min at 25 degrees C. Replacement of K+ with Na+ effectively prevented the lysis by SCN-.K+ salts of NO3-, Br- and I-, however, induced no significant lysis. In electron micrographs, a prolonged exposure of the cells of V. alginolyticus to 1.0 M KSCN displaced the nucleoplasm to maintain close contact with the cell membranes. After 40 min of interaction, 50% of the cellular protein, 96% of RNA and 94% of DNA were recovered in the lysed cells. In contrast to lysis in hypotonic conditions, the lysis induced by KSCN is due mainly to a partial release of protein from the cells. V. costicolus  was more susceptible to SCN- than V. alginolyticus, whereas nonhalophilic Escherichia coli was resistant to 1.0 M KSCN. Thus, lysis by SCN- is characteristic of halophilic bacteria and cell membranes of more halophilic bacteria are more susceptible to chaotropic anions. The protective effect of Na+ observed here was considered to be manifested by specific interactions of Na+ with components of cell membranes, thereby rendering their structures resistant to the action of chaotropic anions."}
{"id": "PMID:201301", "title": "[Spectral-kinetic characteristics of the cation-radical of pheophytin a].", "content": "The photochemical generation of pheophytin a cation-radical in acidulated ethanol and aceto nitril has been studied by the method of flash-photolysis. The bands with maxima at 450, 580 and 800 nm correspond to pheophytin a cation-radical in the differential absorption spectra. The efficient rate constants of pheophytin a triplet state desactivation in ethanol, acetonitril, aceton have the following values: 1.5.10(4), 9.10(3), 8.7.10(3) sec(-1) correspondingly. The rate constant of electron transfer from pheophytin a to p-benzoqui-none in ethanol solutions is 7.8.10(9) l/m.sec. The recombination constants of pheophytin a cation-radical with Q-in acetonitril, and with quinone neutral (QH) in acidulated ethanol have the following values: 5.10(9) and 2.10(9) l/m.sec correspondingly.", "contents": "[Spectral-kinetic characteristics of the cation-radical of pheophytin a]. The photochemical generation of pheophytin a cation-radical in acidulated ethanol and aceto nitril has been studied by the method of flash-photolysis. The bands with maxima at 450, 580 and 800 nm correspond to pheophytin a cation-radical in the differential absorption spectra. The efficient rate constants of pheophytin a triplet state desactivation in ethanol, acetonitril, aceton have the following values: 1.5.10(4), 9.10(3), 8.7.10(3) sec(-1) correspondingly. The rate constant of electron transfer from pheophytin a to p-benzoqui-none in ethanol solutions is 7.8.10(9) l/m.sec. The recombination constants of pheophytin a cation-radical with Q-in acetonitril, and with quinone neutral (QH) in acidulated ethanol have the following values: 5.10(9) and 2.10(9) l/m.sec correspondingly."}
{"id": "PMID:201305", "title": "[Effect of coenzyme on conformational stability of glyceraldehyde-3-phosphate dehydrogenase from muscles of ecto- and endothermic animals].", "content": "The stabilizing effect of the coenzyme (NAD) on the structure of glyceraldehyde-3-phosphate dehydrogenase from lamprey and porcine muscles with respect to proteolysis and heat denaturation was studied. The process of heat denaturation was followed by the changes in specific activity of the enzymes; that of proteolysis--by the changes in specific activity and circular dichroism. It was shown that in both cases NAD at saturating concentration exerts a far weaker stabilizing effect on the structure of glyceraldehyde-3-phosphate dehydrogenase from lamprey muscle than on that of the porcine muscle enzyme. The coensyme-dependent stabilization of lamprey muscle glyceraldehyde-3-phosphate dehydrogenase does not differ from that of mammalian muscle enzyme. Possible interrelationship between the phenomenon observed and the molecular mechanism of thermal adaptation in the cold-blooded animals is discussed.", "contents": "[Effect of coenzyme on conformational stability of glyceraldehyde-3-phosphate dehydrogenase from muscles of ecto- and endothermic animals]. The stabilizing effect of the coenzyme (NAD) on the structure of glyceraldehyde-3-phosphate dehydrogenase from lamprey and porcine muscles with respect to proteolysis and heat denaturation was studied. The process of heat denaturation was followed by the changes in specific activity of the enzymes; that of proteolysis--by the changes in specific activity and circular dichroism. It was shown that in both cases NAD at saturating concentration exerts a far weaker stabilizing effect on the structure of glyceraldehyde-3-phosphate dehydrogenase from lamprey muscle than on that of the porcine muscle enzyme. The coensyme-dependent stabilization of lamprey muscle glyceraldehyde-3-phosphate dehydrogenase does not differ from that of mammalian muscle enzyme. Possible interrelationship between the phenomenon observed and the molecular mechanism of thermal adaptation in the cold-blooded animals is discussed."}
{"id": "PMID:201302", "title": "[Model of electrical feedback mechanisms through chemical synapses].", "content": "The model of excitatory chemical synapse is proposed in which the feed-back between the post- and presynaptic neurones is carried out by means of synaptic current generated by postsynaptic neurone. In the model, the potential drop generated by this current along the intercellular gap near the activated synapse (RIII) evokes additional depolarization of presynaptic membrane and thus stimulates the additional release of transmitter (fig. 1, A and B). The feed-back, which increases the steepness of transfer function between pre- and postsynaptic neurones is the more effective the higher the resistance of intercellular gap (fig. 2 and 3, B). is very low, so that activation of synapse is unable to change significantly its membrane potential (V2), the feed-back is the most effective, as revealed in additional depolarization of presynaptic membrane (VII in fig. 3, A). In inhibitory synapse the feed-back by electrical current is negative one.", "contents": "[Model of electrical feedback mechanisms through chemical synapses]. The model of excitatory chemical synapse is proposed in which the feed-back between the post- and presynaptic neurones is carried out by means of synaptic current generated by postsynaptic neurone. In the model, the potential drop generated by this current along the intercellular gap near the activated synapse (RIII) evokes additional depolarization of presynaptic membrane and thus stimulates the additional release of transmitter (fig. 1, A and B). The feed-back, which increases the steepness of transfer function between pre- and postsynaptic neurones is the more effective the higher the resistance of intercellular gap (fig. 2 and 3, B). is very low, so that activation of synapse is unable to change significantly its membrane potential (V2), the feed-back is the most effective, as revealed in additional depolarization of presynaptic membrane (VII in fig. 3, A). In inhibitory synapse the feed-back by electrical current is negative one."}
{"id": "PMID:201306", "title": "[Properties of mitochondria from cells of the \"fermentative\" variant of Endomyces magnusii].", "content": "The properties of mitochondria from the cells of the \"fermentative\" variant of End. magnusii were studied. The induced fermentative transformation was brought about by a non-balanced vitamin cultivation. It was shown that the \"fermentative\" variant of End. magnusii represents an interesting model, in which the energy required for the cell functioning is provided for by a high fermentative activity and a normally functioning respiratory chain. The \"fermentative\" variant mitochondria were tightly coupled and possessed theoretical efficiency during oxidation of NAD-dependent substrates, which suggested the existence of all the three sites of energy coupling and phosphorylation at the substrate level. A specificity of energy regulation of the End. magnusii \"fermentative\" variant mitochondria, e. g. tight coupling during oxidation of succinate and lack of tight coupling during oxidation of exogenous NADH, is discussed. The tight coupling during succinate oxidation is confirmed by the observation of reverse electron transfer. Thus, the energy-dependent reduction of NAD during succinate oxidation has been firstly demonstrated for the mitochondria of yeast grown on a fermentable substrate.", "contents": "[Properties of mitochondria from cells of the \"fermentative\" variant of Endomyces magnusii]. The properties of mitochondria from the cells of the \"fermentative\" variant of End. magnusii were studied. The induced fermentative transformation was brought about by a non-balanced vitamin cultivation. It was shown that the \"fermentative\" variant of End. magnusii represents an interesting model, in which the energy required for the cell functioning is provided for by a high fermentative activity and a normally functioning respiratory chain. The \"fermentative\" variant mitochondria were tightly coupled and possessed theoretical efficiency during oxidation of NAD-dependent substrates, which suggested the existence of all the three sites of energy coupling and phosphorylation at the substrate level. A specificity of energy regulation of the End. magnusii \"fermentative\" variant mitochondria, e. g. tight coupling during oxidation of succinate and lack of tight coupling during oxidation of exogenous NADH, is discussed. The tight coupling during succinate oxidation is confirmed by the observation of reverse electron transfer. Thus, the energy-dependent reduction of NAD during succinate oxidation has been firstly demonstrated for the mitochondria of yeast grown on a fermentable substrate."}
{"id": "PMID:201307", "title": "[Lipid dependence of mitochondrial monoamine oxidase from rat hepatoma 27 with the use of rat liver lipid exchange proteins].", "content": "The ability of liver lipid exchange proteins to introduce foreign phospholipids into intact mitochondria was used for a study of the lipid dependence of monoamine oxidase. Introduction of exogenous phosphatidylcholine into rat hepatoma mitochondria, in which both the monoamine oxidase activity and the phosphatidylcholine content are comparatively low, leads to considerable activation of the enzyme. The introduction of exogeneous phosphatidylserine, phosphatidylethanolamine and cardiolipin has no activating effect. This indicates that the decreased activity of monoamine oxidase in the hepatoma may be due to a low amount of phosphatidylcholine. The method described allows the study in situ of the lipid dependence of non-solubilized membrane-bound enzymes.", "contents": "[Lipid dependence of mitochondrial monoamine oxidase from rat hepatoma 27 with the use of rat liver lipid exchange proteins]. The ability of liver lipid exchange proteins to introduce foreign phospholipids into intact mitochondria was used for a study of the lipid dependence of monoamine oxidase. Introduction of exogenous phosphatidylcholine into rat hepatoma mitochondria, in which both the monoamine oxidase activity and the phosphatidylcholine content are comparatively low, leads to considerable activation of the enzyme. The introduction of exogeneous phosphatidylserine, phosphatidylethanolamine and cardiolipin has no activating effect. This indicates that the decreased activity of monoamine oxidase in the hepatoma may be due to a low amount of phosphatidylcholine. The method described allows the study in situ of the lipid dependence of non-solubilized membrane-bound enzymes."}
{"id": "PMID:201303", "title": "[Chemical characteristics of conformationally-disequilibrium states of metal-containing proteins].", "content": "Properties of conformation-out-equilibrium states of several iron containing proteins, for example, induced by fast changes of active site were investigated. It was shown that structure and chemical properties of out-of-equilbrium states can differ considerably from the equilibrium ones. Spectral characteristics and reactional ability of these molecules change in the way of slow (up to 10(-1)s) conformational relaxation, continuously approaching the equilibrium values.", "contents": "[Chemical characteristics of conformationally-disequilibrium states of metal-containing proteins]. Properties of conformation-out-equilibrium states of several iron containing proteins, for example, induced by fast changes of active site were investigated. It was shown that structure and chemical properties of out-of-equilbrium states can differ considerably from the equilibrium ones. Spectral characteristics and reactional ability of these molecules change in the way of slow (up to 10(-1)s) conformational relaxation, continuously approaching the equilibrium values."}
{"id": "PMID:201308", "title": "[Amino acid sequence of corticotropins from seiwhale (Balaenoptera borealis) and pinwhale (Balaenoptera physalus)].", "content": "The corticotropins from two species of whales, e. g. seiwhale (Balaenoptera borealis) and finwhale (Balaenoptera physalus) were subjected to hydrolysis by trypsin, chymotrypsin and pepsin. The peptide fragments were separated by gel-filtration through Sephadex and partition paper chromatography. The study of the amino acid sequence of the peptides obtained allowed to establish the primary structure of corticotropin from both species, which was found structurally identical to human corticotropin.", "contents": "[Amino acid sequence of corticotropins from seiwhale (Balaenoptera borealis) and pinwhale (Balaenoptera physalus)]. The corticotropins from two species of whales, e. g. seiwhale (Balaenoptera borealis) and finwhale (Balaenoptera physalus) were subjected to hydrolysis by trypsin, chymotrypsin and pepsin. The peptide fragments were separated by gel-filtration through Sephadex and partition paper chromatography. The study of the amino acid sequence of the peptides obtained allowed to establish the primary structure of corticotropin from both species, which was found structurally identical to human corticotropin."}
{"id": "PMID:201309", "title": "[Interaction of 8-substituted derivatives and adenosine-3',5'-cyclophosphate esters with protein kinase from pig brain].", "content": "A synthesis of previously unknown 8-substituted derivatives and alkyl esters of cyclic adenosine-3',5'-monophosphate, containing reactive groups, was carried out. The interaction of the compounds obtained with a homogeneous preparation of protein kinase from pig brain was studied. It was found that all compounds, with the exception of neutral esters of 3',5'-AMP, activate the enzyme and competitively inhibit 3H-labelled 3',5'-cAMP binding by the regulatory subunit of protein kinase. The activating effect and affinity of 8-(beta-aminoethylamino)-3',5'-cAMP for protein kinase was 10 times lower than that for 3',5'-cAMP and other 8-substituted derivatives of the cyclic nucleotide. It was found that 8-(N-chloroacetylaminoethylamino)-3',5'-cAMP interaction with the enzyme is of irreversible type, which suggest covalent blocking of the nucleophilic group of the 3',5'-cAMP binding site of protein kinase. The data obtained indicate that the 3',5'-cAMP molecule is bound to the regulatory site of protein kinase in the syn-conformation. The previously made assumption on the crucial importance of the negative charge in the 3',5'-cyclophosphate system for the interaction of cyclic AMP with the regulatory subunit of protein kinase has been thus confirmed.", "contents": "[Interaction of 8-substituted derivatives and adenosine-3',5'-cyclophosphate esters with protein kinase from pig brain]. A synthesis of previously unknown 8-substituted derivatives and alkyl esters of cyclic adenosine-3',5'-monophosphate, containing reactive groups, was carried out. The interaction of the compounds obtained with a homogeneous preparation of protein kinase from pig brain was studied. It was found that all compounds, with the exception of neutral esters of 3',5'-AMP, activate the enzyme and competitively inhibit 3H-labelled 3',5'-cAMP binding by the regulatory subunit of protein kinase. The activating effect and affinity of 8-(beta-aminoethylamino)-3',5'-cAMP for protein kinase was 10 times lower than that for 3',5'-cAMP and other 8-substituted derivatives of the cyclic nucleotide. It was found that 8-(N-chloroacetylaminoethylamino)-3',5'-cAMP interaction with the enzyme is of irreversible type, which suggest covalent blocking of the nucleophilic group of the 3',5'-cAMP binding site of protein kinase. The data obtained indicate that the 3',5'-cAMP molecule is bound to the regulatory site of protein kinase in the syn-conformation. The previously made assumption on the crucial importance of the negative charge in the 3',5'-cyclophosphate system for the interaction of cyclic AMP with the regulatory subunit of protein kinase has been thus confirmed."}
{"id": "PMID:201310", "title": "Identification of microcrystals in synovial fluids by combined scanning electron microscopy and x-ray diffraction : application to triclinic calcium pyrophosphate dihydrate.", "content": "We report a method for studying microcrystals which combines scanning electron microscopy, electron-dispersive X-ray analysis, and X-ray diffraction. Application of all three techniques to the same crystalline bodies permits correlation of their three-dimensional morphology at high magnification with unambiguous identification by means of their crystallographic properties. The method was applied to triclinic calcium pyrophosphate dihydrate.", "contents": "Identification of microcrystals in synovial fluids by combined scanning electron microscopy and x-ray diffraction : application to triclinic calcium pyrophosphate dihydrate. We report a method for studying microcrystals which combines scanning electron microscopy, electron-dispersive X-ray analysis, and X-ray diffraction. Application of all three techniques to the same crystalline bodies permits correlation of their three-dimensional morphology at high magnification with unambiguous identification by means of their crystallographic properties. The method was applied to triclinic calcium pyrophosphate dihydrate."}
{"id": "PMID:201311", "title": "Functional abnormalities of neutrophils in cancer patients : inefficient phagocytosis and reverse endocytosis.", "content": "A study of neutrophil functions has been performed in 17 patients with advanced cancer and in 21 controls. Their phagocytic activity, their index of reduction of NBT and their myeloperoxidase activity were examined. The reslts suggest that cancer patients might have a \"factor\" or \"factors\" in their plasma which interfereu (s) with phagocytosis and which promote (s) exocytosis of lysosomal enzymes (\"reverse endocytosis\") from from autologous polymorphonuclear leucocytes as well as from cells obtained from normal healthy donors.", "contents": "Functional abnormalities of neutrophils in cancer patients : inefficient phagocytosis and reverse endocytosis. A study of neutrophil functions has been performed in 17 patients with advanced cancer and in 21 controls. Their phagocytic activity, their index of reduction of NBT and their myeloperoxidase activity were examined. The reslts suggest that cancer patients might have a \"factor\" or \"factors\" in their plasma which interfereu (s) with phagocytosis and which promote (s) exocytosis of lysosomal enzymes (\"reverse endocytosis\") from from autologous polymorphonuclear leucocytes as well as from cells obtained from normal healthy donors."}
{"id": "PMID:201312", "title": "[Changes in several lipid metabolism indices following death and resuscitation].", "content": "The lipolytic activity in the adipose tissue, unesterified fatty acids (UFA) in the blood and adipose tissue, as well as ketone bodies and beta-lipoproteins in the blood were determined in dogs during dying of acute blood loss and the restorative period after the revival of the organism. During agony the activation of lipolysis in the adipose tissue, a decrease of UFA and beta-lipoproteins and an increase of ketane bodies contents in the blood were detected. At the end of the third minute of clinical death there occurred a depression of lipolysis and an increase of UFA content in the adipose tissue. One hour after the revival of the organism the blood UFA content and beta-proteins decrease, but the ketone bodies content rises; simultaneously there occurs some reduction of lipolytic activity of the adipose tissue. At the late postreanimation period (in 1, 3, and 7 days) an activation of lipolysis in the adipose tissue and an increase of UFA, ketone bodies, and beta-lipoproteins content in the blood was noted. The adipose tissue UFA content was low during the postreanimation period. The given results have shown that the changes in the lipid metabolism could play some role in the pathogenesis of non-reversibility during dying and after the revival of the organism.", "contents": "[Changes in several lipid metabolism indices following death and resuscitation]. The lipolytic activity in the adipose tissue, unesterified fatty acids (UFA) in the blood and adipose tissue, as well as ketone bodies and beta-lipoproteins in the blood were determined in dogs during dying of acute blood loss and the restorative period after the revival of the organism. During agony the activation of lipolysis in the adipose tissue, a decrease of UFA and beta-lipoproteins and an increase of ketane bodies contents in the blood were detected. At the end of the third minute of clinical death there occurred a depression of lipolysis and an increase of UFA content in the adipose tissue. One hour after the revival of the organism the blood UFA content and beta-proteins decrease, but the ketone bodies content rises; simultaneously there occurs some reduction of lipolytic activity of the adipose tissue. At the late postreanimation period (in 1, 3, and 7 days) an activation of lipolysis in the adipose tissue and an increase of UFA, ketone bodies, and beta-lipoproteins content in the blood was noted. The adipose tissue UFA content was low during the postreanimation period. The given results have shown that the changes in the lipid metabolism could play some role in the pathogenesis of non-reversibility during dying and after the revival of the organism."}
{"id": "PMID:201313", "title": "[Role of corticosteroids in regulating splenic nucleic acid metabolism following severe mechanical injury].", "content": "The author studied the RNA and DNA concentration in the spleen of control rats, which had been adrenalectomized and had received ACTH before the trauma and 10 min, 5 and 10 hours after the beginning of the limbs' soft tissue crushing. The changes of nucleic acid metabolization in the spleen during the trauma were caused by the influence of corticosteroid hormones.", "contents": "[Role of corticosteroids in regulating splenic nucleic acid metabolism following severe mechanical injury]. The author studied the RNA and DNA concentration in the spleen of control rats, which had been adrenalectomized and had received ACTH before the trauma and 10 min, 5 and 10 hours after the beginning of the limbs' soft tissue crushing. The changes of nucleic acid metabolization in the spleen during the trauma were caused by the influence of corticosteroid hormones."}
{"id": "PMID:201315", "title": "[Effect of thyrotropin releasing hormone thyroxine on the activity of cytochrome oxidase in rat adenohypophysis].", "content": "Thyrotropin releasing-hormone (TRH) increased the activity of cytrochrome C oxidase in a concentration of 0.01 and 1.0 microgram/ml in the adenohypophysis of rats fed methylthiouracil for 6 weeks. This effect of TRH on the activity of the enzyme was blocked with T4 added to the incubation medium in a concentration of 20 microgram/ml. Actinomycin D (20 MICrogram/ml) prevented the block of the enzyme with thyroxin. In a concentration of 0.01 microgram/ml TRH, and in a concentration of 2.0 microgram/ml T4 failed to change the activity of cytochrome oxidase in the adenohypophysis of normal and partially thyroidectomized rats.", "contents": "[Effect of thyrotropin releasing hormone thyroxine on the activity of cytochrome oxidase in rat adenohypophysis]. Thyrotropin releasing-hormone (TRH) increased the activity of cytrochrome C oxidase in a concentration of 0.01 and 1.0 microgram/ml in the adenohypophysis of rats fed methylthiouracil for 6 weeks. This effect of TRH on the activity of the enzyme was blocked with T4 added to the incubation medium in a concentration of 20 microgram/ml. Actinomycin D (20 MICrogram/ml) prevented the block of the enzyme with thyroxin. In a concentration of 0.01 microgram/ml TRH, and in a concentration of 2.0 microgram/ml T4 failed to change the activity of cytochrome oxidase in the adenohypophysis of normal and partially thyroidectomized rats."}
{"id": "PMID:201316", "title": "[Organ and tissue cyclic adenosine-3', 5'-monophosphate during the process of the body's adaptation to extreme factors].", "content": "Various by nature extreme factors (hypoxic hypoxia, CO intoxication, chemical influence, noise and hypokinesia) caused similar changes in cAMP levels in different organs of albino rats (liver, the great cerebral hemispheres, heart). There was a significant increase in cAMP concentrations during the first stages of the influence and a progressive fall when the influence was continued. This fall was particularly expressed when the extreme factors used were of marked intensity. The authors consider the universality of the ascertained regularity to be a reflection of one of the central adaptive mechanisms of cell and the organism as a whole.", "contents": "[Organ and tissue cyclic adenosine-3', 5'-monophosphate during the process of the body's adaptation to extreme factors]. Various by nature extreme factors (hypoxic hypoxia, CO intoxication, chemical influence, noise and hypokinesia) caused similar changes in cAMP levels in different organs of albino rats (liver, the great cerebral hemispheres, heart). There was a significant increase in cAMP concentrations during the first stages of the influence and a progressive fall when the influence was continued. This fall was particularly expressed when the extreme factors used were of marked intensity. The authors consider the universality of the ascertained regularity to be a reflection of one of the central adaptive mechanisms of cell and the organism as a whole."}
{"id": "PMID:201317", "title": "[Influence of single and repeated pregnancies on the incidence of primary tumors induced by SV40 virus in hamsters].", "content": "The influence of the single and repeated pregnancies on the SV40-induced carcinogenesis in Syrian hamsters was studied. It was shown that the frequency of the primary tumours in females which become pregnant 1-5 times during the latent period of SV40 carcinogenesis was significantly lower in comparison with virgin females observed in the same experiment. However, these differences apparently had no connection with the immunization of multiparous females with embryonic antigens, as the frequency and the time of appearance of primary tumours in males were the same as in multiparous females.", "contents": "[Influence of single and repeated pregnancies on the incidence of primary tumors induced by SV40 virus in hamsters]. The influence of the single and repeated pregnancies on the SV40-induced carcinogenesis in Syrian hamsters was studied. It was shown that the frequency of the primary tumours in females which become pregnant 1-5 times during the latent period of SV40 carcinogenesis was significantly lower in comparison with virgin females observed in the same experiment. However, these differences apparently had no connection with the immunization of multiparous females with embryonic antigens, as the frequency and the time of appearance of primary tumours in males were the same as in multiparous females."}
{"id": "PMID:201319", "title": "A conformational analysis for leucine-enkephalin using activity and binding data of synthetic analogues.", "content": "1. Leucine-enkephalin and some analogues were assayed for activity in vitro on the mouse vas deferens and for binding to opiate receptors from rat brain. 2. The experimental data were analysed in terms of the stringency for glycine, a D-amino acid or an L-amino acid at each position in the peptide. 3. The observed configurational specificity was compared with the stringency that would be predicted to occur if enkephalin adopted certain hydrogen-bonded conformations at the receptor. 4. A small subset of the conformations examined was found to be compatible with the experimental data.", "contents": "A conformational analysis for leucine-enkephalin using activity and binding data of synthetic analogues. 1. Leucine-enkephalin and some analogues were assayed for activity in vitro on the mouse vas deferens and for binding to opiate receptors from rat brain. 2. The experimental data were analysed in terms of the stringency for glycine, a D-amino acid or an L-amino acid at each position in the peptide. 3. The observed configurational specificity was compared with the stringency that would be predicted to occur if enkephalin adopted certain hydrogen-bonded conformations at the receptor. 4. A small subset of the conformations examined was found to be compatible with the experimental data."}
{"id": "PMID:201320", "title": "Cannabis, catecholamines, rapid eye movement sleep and aggressive behaviour.", "content": "1. Previous work from our laboratory has shown that cannabis induces aggressive behaviour in rats that have been deprived of rapid eye movement (REM) sleep. It was suggested that this effect was related to brain catecholamines, with dopamine playing an agonist role and noradrenaline an inhibitory one. The present paper describes new experiments dealing with this subject. 2. Previous REM sleep-deprivation enhanced both delta9-tetrahydrocannabinol (THC)-induced hypothermia and nomifensine effects on aggressive behaviour. 3. A marihuana extract decreased brain dopamine turnover in REM sleep-deprived rats, an effect not observed in non-deprived rats. Noradrenaline metabolism was not altered. 4. Fighting behaviour was elicited in REM sleep-deprived rats treated with 4 different dopamine-beta-hydroxylase inhibitors. 5. Apomorphine, nomifensine and delta9-THC administered to non-deprived rats pretreated with bis(4-methyl-1-homopiperanzinyl-thiocarbonyl) disulphide (Fla-63), induced fighting behaviour. 6. Nomifensine and apomorphine induced fighting in non-deprived rats pretreated with delta9-THC. 7. Clonidine inhibited the fighting elicited in REM sleep-deprived rats by either delta9-THC or Fla-63 pretreatment. 8. The data are discussed in terms of the influence of REM sleep-deprivation (or the stress associated with deprivation) on the response to dopaminergic drugs and cannabis. Taken together they emphasize the participation of brain dopamine and noradrenaline systems in the aggressive behaviour studied.", "contents": "Cannabis, catecholamines, rapid eye movement sleep and aggressive behaviour. 1. Previous work from our laboratory has shown that cannabis induces aggressive behaviour in rats that have been deprived of rapid eye movement (REM) sleep. It was suggested that this effect was related to brain catecholamines, with dopamine playing an agonist role and noradrenaline an inhibitory one. The present paper describes new experiments dealing with this subject. 2. Previous REM sleep-deprivation enhanced both delta9-tetrahydrocannabinol (THC)-induced hypothermia and nomifensine effects on aggressive behaviour. 3. A marihuana extract decreased brain dopamine turnover in REM sleep-deprived rats, an effect not observed in non-deprived rats. Noradrenaline metabolism was not altered. 4. Fighting behaviour was elicited in REM sleep-deprived rats treated with 4 different dopamine-beta-hydroxylase inhibitors. 5. Apomorphine, nomifensine and delta9-THC administered to non-deprived rats pretreated with bis(4-methyl-1-homopiperanzinyl-thiocarbonyl) disulphide (Fla-63), induced fighting behaviour. 6. Nomifensine and apomorphine induced fighting in non-deprived rats pretreated with delta9-THC. 7. Clonidine inhibited the fighting elicited in REM sleep-deprived rats by either delta9-THC or Fla-63 pretreatment. 8. The data are discussed in terms of the influence of REM sleep-deprivation (or the stress associated with deprivation) on the response to dopaminergic drugs and cannabis. Taken together they emphasize the participation of brain dopamine and noradrenaline systems in the aggressive behaviour studied."}
{"id": "PMID:201321", "title": "Coronary reactions to cardiac hyperactivity and to hypoxia in isolated perfused heart of rat.", "content": "1. Continuous recording of cardiac force of contraction, heart rate and coronary flow from isolated perfused hearts of rats was used to study coronary reactions: (a) to cardiostimulation with noradrenaline, CaCl2, or electrically induced tachycardia; (b) to short duration stoppage of coronary inflow (hypoxia). 2. The heart rate was controlled by electrical pacing. Coronary vasodilatation resulted from cardiostimulation or hypoxia. This coronary response was greater at higher heart rates. 3. In parallel experiments administration of noradrenaline to hearts paced at different frequencies resulted in a rate-dependent elevation of adenosine-3',5'-cyclic monophosphate (cyclic AMP). 4. Duration of hypoxia leading to different degrees of reactive hyperaemia did not change the cardiac cyclic AMP levels. 5. Coronary vasodilatation due to increased cardiac metabolism produced by noradrenaline, Ca2+ or tachycardia was enhanced by the phosphodiesterase inhibitors diazoxide and papaverine while it was inhibited during the administration of prostaglandin E2.6. Reactive hyperaemia was unaffected by diazoxide, papaverine or prostaglandin E2. 7. Catecholamine depletion by reserpine did not influence metabolic coronary dilatation nor the reactive hyperaemic responses. 8. We postulate that there are at least two types of coronary reactions: one in response to hypoxia, 'reactive hyperaemia', and another resulting from cardiac hyperactivity, 'metabolic coronary dilatation'. The latter, blocked by prostaglandin E2 and enhanced by diazoxide or papaverine, would be triggered by cyclic AMP while reactive hyperaemia would result from other mechanisms.", "contents": "Coronary reactions to cardiac hyperactivity and to hypoxia in isolated perfused heart of rat. 1. Continuous recording of cardiac force of contraction, heart rate and coronary flow from isolated perfused hearts of rats was used to study coronary reactions: (a) to cardiostimulation with noradrenaline, CaCl2, or electrically induced tachycardia; (b) to short duration stoppage of coronary inflow (hypoxia). 2. The heart rate was controlled by electrical pacing. Coronary vasodilatation resulted from cardiostimulation or hypoxia. This coronary response was greater at higher heart rates. 3. In parallel experiments administration of noradrenaline to hearts paced at different frequencies resulted in a rate-dependent elevation of adenosine-3',5'-cyclic monophosphate (cyclic AMP). 4. Duration of hypoxia leading to different degrees of reactive hyperaemia did not change the cardiac cyclic AMP levels. 5. Coronary vasodilatation due to increased cardiac metabolism produced by noradrenaline, Ca2+ or tachycardia was enhanced by the phosphodiesterase inhibitors diazoxide and papaverine while it was inhibited during the administration of prostaglandin E2.6. Reactive hyperaemia was unaffected by diazoxide, papaverine or prostaglandin E2. 7. Catecholamine depletion by reserpine did not influence metabolic coronary dilatation nor the reactive hyperaemic responses. 8. We postulate that there are at least two types of coronary reactions: one in response to hypoxia, 'reactive hyperaemia', and another resulting from cardiac hyperactivity, 'metabolic coronary dilatation'. The latter, blocked by prostaglandin E2 and enhanced by diazoxide or papaverine, would be triggered by cyclic AMP while reactive hyperaemia would result from other mechanisms."}
{"id": "PMID:201331", "title": "Inhibition of plasma cyclic AMP, glucose and cortisol response to surgery by epidural analgesia.", "content": "Cyclic AMP, glucose and cortisol in plasma were measured in three groups of patients undergoing hysterectomy. The operations were performed under general anaesthesia, under general anaesthesia combined with epidural analgesia and under epidural analgesia alone. Surgery elicited a significant rise in plasma cyclic AMP, glucose and cortisol when performed under general anaesthesia alone. Epidural analgesia extending from T4-6 to S5 combined with general anaesthesia abolished the rise in cyclic AMP and reduced the increase in glucose and cortisol and epidural analgesia alone extending from T4 to S5 blocked the rise in glucose and cortisol as well as that in cyclic AMP. The results support the theory that afferent nerve impulses from the area of trauma are of major importance for the catabolic state induced by surgical procedures and indicate that anaesthetic management which includes blockade of afferent nerve impulses which includes blockade of afferent nerve impulses from the area of trauma can be reduce the catabolic response to surgery. These observations could be of value in the operative management of patients with diabetes mellitus and possibly in other groups by patients with a high surgical morbidity.", "contents": "Inhibition of plasma cyclic AMP, glucose and cortisol response to surgery by epidural analgesia. Cyclic AMP, glucose and cortisol in plasma were measured in three groups of patients undergoing hysterectomy. The operations were performed under general anaesthesia, under general anaesthesia combined with epidural analgesia and under epidural analgesia alone. Surgery elicited a significant rise in plasma cyclic AMP, glucose and cortisol when performed under general anaesthesia alone. Epidural analgesia extending from T4-6 to S5 combined with general anaesthesia abolished the rise in cyclic AMP and reduced the increase in glucose and cortisol and epidural analgesia alone extending from T4 to S5 blocked the rise in glucose and cortisol as well as that in cyclic AMP. The results support the theory that afferent nerve impulses from the area of trauma are of major importance for the catabolic state induced by surgical procedures and indicate that anaesthetic management which includes blockade of afferent nerve impulses which includes blockade of afferent nerve impulses from the area of trauma can be reduce the catabolic response to surgery. These observations could be of value in the operative management of patients with diabetes mellitus and possibly in other groups by patients with a high surgical morbidity."}
{"id": "PMID:201340", "title": "Reversible blockade of PGO waves and concomitant modifications of thalamic unit activity in chronic cats.", "content": "The reversible blockade of geniculate PGO waves was carried out by localized cooling of the ponto-geniculate pathways during paradoxical sleep in chronic cats. In parallel, long-term recordings of unit activity were performed in non-specific visuooculomotor thalamic structures where no PGO waves occurred. Blockade of geniculate PGO waves is concomitant with a preferential modification of the phasic discharge of the unit activity (i.e. time-locked with rapid eye movements) when compared to the tonic discharge (i.e. without rapid eye movements). These results suggest that pontine generators of PGO waves could act upon every neuron of the central nervous system. The significance of such an extensive ascending system, the blockade of which does not interrupt paradoxical sleep episodes, still remains puzzling.", "contents": "Reversible blockade of PGO waves and concomitant modifications of thalamic unit activity in chronic cats. The reversible blockade of geniculate PGO waves was carried out by localized cooling of the ponto-geniculate pathways during paradoxical sleep in chronic cats. In parallel, long-term recordings of unit activity were performed in non-specific visuooculomotor thalamic structures where no PGO waves occurred. Blockade of geniculate PGO waves is concomitant with a preferential modification of the phasic discharge of the unit activity (i.e. time-locked with rapid eye movements) when compared to the tonic discharge (i.e. without rapid eye movements). These results suggest that pontine generators of PGO waves could act upon every neuron of the central nervous system. The significance of such an extensive ascending system, the blockade of which does not interrupt paradoxical sleep episodes, still remains puzzling."}
{"id": "PMID:201345", "title": "Characterization of a myelin-related fraction (SN 4) isolated from rat forebrain at two developmental stages.", "content": "A myelin-related fraction (SN 4) was isolated from forebrain of 17- and 40-day-old rats. Fraction SN 4 was obtained as a supernatant in a slow speed differential centrifugation of a myelin fraction. In contrast to multilamellar myelin fraction, SN 4 consisted of small vesicular profiles of a mixture of single membranes and some triple-layered structures. All typical myelin components were found in the SN 4 fraction from adult rat brain but their relative proportion was different from that of myelin: Wolfgram protein, myelin glycoproteins and 2',3'-cyclic nucleotide 3'-phosphohydrolase were increased, while basic proteins and proteolipid protein were decreased significantly. In contrast, the lipid composition appeared very similar to the one found in myelin. SN 4 from 17-day-old rat brains was essentially similar to that from adults, except that the major myelin glycoprotein was not enriched in comparison to myelin. Developmental changes found in myelin were also present in the SN 4 fraction. The specific radioactivity of the fucose-labeled major myelin glycoprotein was similar in SN 4 and in myelin. The particular composition of fraction SN 4 suggests that this material is not significantly contaminated by non-myelin-related membranes but rather supports the hypothesis that it could be enriched in a membrane representing a zone of transition during the formation of myelin and which is subjected to a remodelling of its protein components.", "contents": "Characterization of a myelin-related fraction (SN 4) isolated from rat forebrain at two developmental stages. A myelin-related fraction (SN 4) was isolated from forebrain of 17- and 40-day-old rats. Fraction SN 4 was obtained as a supernatant in a slow speed differential centrifugation of a myelin fraction. In contrast to multilamellar myelin fraction, SN 4 consisted of small vesicular profiles of a mixture of single membranes and some triple-layered structures. All typical myelin components were found in the SN 4 fraction from adult rat brain but their relative proportion was different from that of myelin: Wolfgram protein, myelin glycoproteins and 2',3'-cyclic nucleotide 3'-phosphohydrolase were increased, while basic proteins and proteolipid protein were decreased significantly. In contrast, the lipid composition appeared very similar to the one found in myelin. SN 4 from 17-day-old rat brains was essentially similar to that from adults, except that the major myelin glycoprotein was not enriched in comparison to myelin. Developmental changes found in myelin were also present in the SN 4 fraction. The specific radioactivity of the fucose-labeled major myelin glycoprotein was similar in SN 4 and in myelin. The particular composition of fraction SN 4 suggests that this material is not significantly contaminated by non-myelin-related membranes but rather supports the hypothesis that it could be enriched in a membrane representing a zone of transition during the formation of myelin and which is subjected to a remodelling of its protein components."}
{"id": "PMID:201346", "title": "Presynaptic origin of penicillin after discharges at mammalian nerve terminals.", "content": "The site of origin and mechanism underlying the generation of repetitive after-discharges produced by penicillin was studied in the isolated rat phrenic nerve-hemidiaphragm preparation. Application of low concentrations of sodium penicillin to the bathing solution initiated bursts of antidromic action potentials originating at or near the motor nerve terminals following single orthodromic stimuli to the nerve. Afterdischarges could not be elicited by direct stimulation of the muscle fibers alone, or when the nerve trunk was isolated from the neuromuscular junction and exposed to penicillin. D-Tubocurarine applied in doses sufficient to abolish postsynaptic responses did not diminish penicillin-induced after discharges. At concentrations which most reliably produced repetitive firing (5000 IU/ml; 8.5 mM), penicillin did not accelerate the frequency of spontaneous transmitter release (MEPPs), yet significantly increased the relative excitability of nerve endings to extracellular stimulation. It is concluded that penicillin acts directly and preferentially on presynaptic nerve terminals to induce repetitive afterdischarges which arise independently of postsynaptic depolarization, transmitter-mediated potassium efflux, or muscle fiber contraction. The results suggest that the convulsant effects of penicillin at a mammalian neuromuscular junction are due to non-depolarizing alterations in the intrinsic excitability of the terminal membrane which increase the probability of suprathreshold depolarizations during the recovery period of spike electrogenesis. Several models of the mechanisms which might produce hyperexcitability at presynaptic nerve terminals are discussed.", "contents": "Presynaptic origin of penicillin after discharges at mammalian nerve terminals. The site of origin and mechanism underlying the generation of repetitive after-discharges produced by penicillin was studied in the isolated rat phrenic nerve-hemidiaphragm preparation. Application of low concentrations of sodium penicillin to the bathing solution initiated bursts of antidromic action potentials originating at or near the motor nerve terminals following single orthodromic stimuli to the nerve. Afterdischarges could not be elicited by direct stimulation of the muscle fibers alone, or when the nerve trunk was isolated from the neuromuscular junction and exposed to penicillin. D-Tubocurarine applied in doses sufficient to abolish postsynaptic responses did not diminish penicillin-induced after discharges. At concentrations which most reliably produced repetitive firing (5000 IU/ml; 8.5 mM), penicillin did not accelerate the frequency of spontaneous transmitter release (MEPPs), yet significantly increased the relative excitability of nerve endings to extracellular stimulation. It is concluded that penicillin acts directly and preferentially on presynaptic nerve terminals to induce repetitive afterdischarges which arise independently of postsynaptic depolarization, transmitter-mediated potassium efflux, or muscle fiber contraction. The results suggest that the convulsant effects of penicillin at a mammalian neuromuscular junction are due to non-depolarizing alterations in the intrinsic excitability of the terminal membrane which increase the probability of suprathreshold depolarizations during the recovery period of spike electrogenesis. Several models of the mechanisms which might produce hyperexcitability at presynaptic nerve terminals are discussed."}
{"id": "PMID:201349", "title": "[Cells with phosphatase activity in the walls of subcutaneous capillaries from normal and inflamed rat tissue].", "content": "In the wall of rat's capillary blood vessels the adenosine triphosphatase is located on the endothelium, the 5'nucleotidase on the perithelial cells. The perithelial cells activities are strong during the inflammatory state, but at the beginning of the phenomenon the nucleotidasic cells become free into the oedematous tissue by preceding and accompagning the fibroblastic differenciation cells.", "contents": "[Cells with phosphatase activity in the walls of subcutaneous capillaries from normal and inflamed rat tissue]. In the wall of rat's capillary blood vessels the adenosine triphosphatase is located on the endothelium, the 5'nucleotidase on the perithelial cells. The perithelial cells activities are strong during the inflammatory state, but at the beginning of the phenomenon the nucleotidasic cells become free into the oedematous tissue by preceding and accompagning the fibroblastic differenciation cells."}
{"id": "PMID:201350", "title": "[Experimental nephrotic syndrome in the rat. Biologic parameters and study of several hydrolases in different purified kidney fractions].", "content": "The induction of nephrotoxic nephritis in rats with rabbit antibodies preparation results in proteinuria, hypoproteinemia and hyperlipidemia with little glomerular lesions. A study of some hydrolases in cortex and medulla on one hand and glomerular and tubules on the other, showed changes in the activities of following enzymes. 1) A 20-30 % decrease in Na+, K+ dependent ATP-ase in whole kidney. 2) A 20 % decrease in beta-galactosidase activity in glomerular and medulla. 3) A 20 % increase of arylsulphatase A activity in tubules. These results are discussed in the light of the present knowledge of sulphatide metabolism in kidney.", "contents": "[Experimental nephrotic syndrome in the rat. Biologic parameters and study of several hydrolases in different purified kidney fractions]. The induction of nephrotoxic nephritis in rats with rabbit antibodies preparation results in proteinuria, hypoproteinemia and hyperlipidemia with little glomerular lesions. A study of some hydrolases in cortex and medulla on one hand and glomerular and tubules on the other, showed changes in the activities of following enzymes. 1) A 20-30 % decrease in Na+, K+ dependent ATP-ase in whole kidney. 2) A 20 % decrease in beta-galactosidase activity in glomerular and medulla. 3) A 20 % increase of arylsulphatase A activity in tubules. These results are discussed in the light of the present knowledge of sulphatide metabolism in kidney."}
{"id": "PMID:201351", "title": "[Effect of NADH and several Krebs cycle substrates on the endogenous metabolism of Pseudomonas fluorescens (type S)].", "content": "Simultaneous addition of succinate (or fumarate) and NADH to a non-proliferating suspension of P. fluorescens results in an enhancement of the oxydation of the endogenous substrates. This conclusion is in accord with the determination of the respiratory and the oxidation quotients of the analysed exogenous substrates.", "contents": "[Effect of NADH and several Krebs cycle substrates on the endogenous metabolism of Pseudomonas fluorescens (type S)]. Simultaneous addition of succinate (or fumarate) and NADH to a non-proliferating suspension of P. fluorescens results in an enhancement of the oxydation of the endogenous substrates. This conclusion is in accord with the determination of the respiratory and the oxidation quotients of the analysed exogenous substrates."}
{"id": "PMID:201352", "title": "[Reduction of adrenaline-dependent lipolysis in the adipose tissue of adrenalectomized dogs by an alpha adrenergic effect].", "content": "In dog, surrenalectomy reduces isoprenalino-depending lipolysis but still more adrenalino-depending lipolysis. Phentolamine potentializes the response to adrenaline but does not that observed with isoprenaline. Surrenalectomy unmasks an alpha adrenergical effect of adrenaline on adipocytes of dog adipose tissue.", "contents": "[Reduction of adrenaline-dependent lipolysis in the adipose tissue of adrenalectomized dogs by an alpha adrenergic effect]. In dog, surrenalectomy reduces isoprenalino-depending lipolysis but still more adrenalino-depending lipolysis. Phentolamine potentializes the response to adrenaline but does not that observed with isoprenaline. Surrenalectomy unmasks an alpha adrenergical effect of adrenaline on adipocytes of dog adipose tissue."}
{"id": "PMID:201353", "title": "Effect of the inhibitor of angiotensin I converting enzyme on endocrine function and renal perfusion in haemorrhagic shock.", "content": "The present study was undertaken to investigate the effect of inhibition of angiotensin I converting enzyme on endocrine responses and renal perfusion in haemorrhagic shock. Plasma levels of vasopressin (VP), aldosterone, and plasma renin activity (PRA), and renal cortical tissue blood flow were measured both in control dogs and in those treated with an inhibitor of angiotensin I converting enzyme (SQ20881). The drug was administered with an intention of preventing vasoconstriction induced by angiotensin II and to improve tissue perfusion. No significant differences were found in plasma levels of vasopressin, aldosterone and plasma renin activity between control and SQ20881-treated groups. Secondary elevation of blood pressure following haemorrhage was significantly delayed and reduced by the administration of the inhibitor. Decrease in renal cortical tissue blood flow was observed in the SQ20881-treated group. It is suggested that angiotension II appears to play a role in spontaneous recovery of arterial blood pressure following haemorrhage. Furthermore, angiotensin II does not seem to play an important role in the stimulation of secretion of vasopressin in response to haemorrhage. Our data failed to demonstrate any favourable effects of inhibition of angiotension I converting enzyme on renal perfusion during haemorrhagic shock in dogs.", "contents": "Effect of the inhibitor of angiotensin I converting enzyme on endocrine function and renal perfusion in haemorrhagic shock. The present study was undertaken to investigate the effect of inhibition of angiotensin I converting enzyme on endocrine responses and renal perfusion in haemorrhagic shock. Plasma levels of vasopressin (VP), aldosterone, and plasma renin activity (PRA), and renal cortical tissue blood flow were measured both in control dogs and in those treated with an inhibitor of angiotensin I converting enzyme (SQ20881). The drug was administered with an intention of preventing vasoconstriction induced by angiotensin II and to improve tissue perfusion. No significant differences were found in plasma levels of vasopressin, aldosterone and plasma renin activity between control and SQ20881-treated groups. Secondary elevation of blood pressure following haemorrhage was significantly delayed and reduced by the administration of the inhibitor. Decrease in renal cortical tissue blood flow was observed in the SQ20881-treated group. It is suggested that angiotension II appears to play a role in spontaneous recovery of arterial blood pressure following haemorrhage. Furthermore, angiotensin II does not seem to play an important role in the stimulation of secretion of vasopressin in response to haemorrhage. Our data failed to demonstrate any favourable effects of inhibition of angiotension I converting enzyme on renal perfusion during haemorrhagic shock in dogs."}
{"id": "PMID:201354", "title": "Avoidance of vascular complications associated with the use of dopamine.", "content": "Dopamine, dihydroxyphenylethylamine has three distinct actions depending on dosage. Low doses in the range of 1-2 mcg/kg/min result in vasodilatation. Medium doses of 2-10 mcg/kg/min increase cardiac output due to beta adrenergic action, while above 10 mcg/kg/min a potent vasoconstrictor effect predominates. Because of this last action great care must be used to avoid extravasation of infusions of dopamine directly into the tissue. Dopamine is a very useful agent but carries great potential to do local damage. Administration through a catheter placed into a large vein is recommended. Should extravasation occur, prompt infiltration of the area with phentolamine and a local anaesthetic, local cooling and regional sympathetic block may reduce the damage. The case is reported of a patient who suffered extensive necrosis in the forearm following local extravasation of dopamine.", "contents": "Avoidance of vascular complications associated with the use of dopamine. Dopamine, dihydroxyphenylethylamine has three distinct actions depending on dosage. Low doses in the range of 1-2 mcg/kg/min result in vasodilatation. Medium doses of 2-10 mcg/kg/min increase cardiac output due to beta adrenergic action, while above 10 mcg/kg/min a potent vasoconstrictor effect predominates. Because of this last action great care must be used to avoid extravasation of infusions of dopamine directly into the tissue. Dopamine is a very useful agent but carries great potential to do local damage. Administration through a catheter placed into a large vein is recommended. Should extravasation occur, prompt infiltration of the area with phentolamine and a local anaesthetic, local cooling and regional sympathetic block may reduce the damage. The case is reported of a patient who suffered extensive necrosis in the forearm following local extravasation of dopamine."}
{"id": "PMID:201358", "title": "Thyroid and breast cancer following childhood radiation.", "content": "A 35-year-old man who received radiation for thymic enlargement as a child and subsequently developed both thyroid and breast cancer is reported. This appears to be the first case in which this association has been reported in a male.", "contents": "Thyroid and breast cancer following childhood radiation. A 35-year-old man who received radiation for thymic enlargement as a child and subsequently developed both thyroid and breast cancer is reported. This appears to be the first case in which this association has been reported in a male."}
{"id": "PMID:201359", "title": "Immunotherapy of a guinea pig hepatoma with living BCG: a frozen liquid and a lyophilized preparation are equally active.", "content": "A freeze dried preparation of BCG with a low ratio of living to dead organisms (LV) was compared to a frozen liquid preparation with high viability (HV) for its ability to eradicate established dermal tumors and microscopic lymph node metastases in guinea pigs. The cure rate achieved by the intralesional injection of LV-BCG did not differ significantly from that of HV-bcg when similar numbers of viable organisms were injected.", "contents": "Immunotherapy of a guinea pig hepatoma with living BCG: a frozen liquid and a lyophilized preparation are equally active. A freeze dried preparation of BCG with a low ratio of living to dead organisms (LV) was compared to a frozen liquid preparation with high viability (HV) for its ability to eradicate established dermal tumors and microscopic lymph node metastases in guinea pigs. The cure rate achieved by the intralesional injection of LV-BCG did not differ significantly from that of HV-bcg when similar numbers of viable organisms were injected."}
{"id": "PMID:201360", "title": "Establishment of an Epstein-Barr virus-negative B-cell lymphoma line from a Japanese Burkitt's lymphoma and its serial passage in hamsters.", "content": "An Epstein-Barr virus (EBV)-negative lymphoma line (JBL) was established in vitro from pleural effusion of an EBV-seropositive 29-year-old Japanese female with Burkitt's lymphoma. JBL cells as well as her original lymphoma cells bore monoclonal surface IgM with lambda light chains. The JBL line grew in single cell suspension with a doubling time of 30 hours. Attempts were made to serially transplant JBL cells in antilymphocyte serum-treated newborn hamsters; intraperitoneal implantation of 1-3 X 10(7) cells gave rise to invasive tumors in all recipients with death after 10 to 14 days. The hamster-passage line, now in the 9th passage, has been converted to an ascitic form with progression to leukemia in some animals. A \"starry sky\" pattern closely resembling the human tumor material was preserved in every tumor through serial animal passage.", "contents": "Establishment of an Epstein-Barr virus-negative B-cell lymphoma line from a Japanese Burkitt's lymphoma and its serial passage in hamsters. An Epstein-Barr virus (EBV)-negative lymphoma line (JBL) was established in vitro from pleural effusion of an EBV-seropositive 29-year-old Japanese female with Burkitt's lymphoma. JBL cells as well as her original lymphoma cells bore monoclonal surface IgM with lambda light chains. The JBL line grew in single cell suspension with a doubling time of 30 hours. Attempts were made to serially transplant JBL cells in antilymphocyte serum-treated newborn hamsters; intraperitoneal implantation of 1-3 X 10(7) cells gave rise to invasive tumors in all recipients with death after 10 to 14 days. The hamster-passage line, now in the 9th passage, has been converted to an ascitic form with progression to leukemia in some animals. A \"starry sky\" pattern closely resembling the human tumor material was preserved in every tumor through serial animal passage."}
{"id": "PMID:201361", "title": "Malignant myoepithelioma of the parotid gland.", "content": "Myoepithelial cells are a significant component of most types of salivary gland neoplasms. A small but increasing number of case reports have also shown that pure myoepitheliomas form a distinct class of neoplasms with unique histological features. Previously reported cases have been either benign or, at most, locally aggressive. We present here a case of a malignant myoepithelioma of the parotid gland, confirmed by electron microscopy, that was locally aggressive and eventually metastasized. Review of this case and of existing reports indicates that myoepitheliomas exhibit a wide range of biological behavior that seems to correlate with their histological appearance.", "contents": "Malignant myoepithelioma of the parotid gland. Myoepithelial cells are a significant component of most types of salivary gland neoplasms. A small but increasing number of case reports have also shown that pure myoepitheliomas form a distinct class of neoplasms with unique histological features. Previously reported cases have been either benign or, at most, locally aggressive. We present here a case of a malignant myoepithelioma of the parotid gland, confirmed by electron microscopy, that was locally aggressive and eventually metastasized. Review of this case and of existing reports indicates that myoepitheliomas exhibit a wide range of biological behavior that seems to correlate with their histological appearance."}
{"id": "PMID:201362", "title": "Extrarenal Wilms' tumor: report of a case and review of the literature.", "content": "A case of an extrarenal Wilms tumor arising in the inguinal region of a 2-month-old boy is described. A review of the literature indicates that nine well-documented cases of extrarenal Wilms tumor have previously been described. Four of these tumors arose within teratomas. The remaining five cases, in which no teratomatous components were encountered, probably arose in embryologic rests of renal tissue.", "contents": "Extrarenal Wilms' tumor: report of a case and review of the literature. A case of an extrarenal Wilms tumor arising in the inguinal region of a 2-month-old boy is described. A review of the literature indicates that nine well-documented cases of extrarenal Wilms tumor have previously been described. Four of these tumors arose within teratomas. The remaining five cases, in which no teratomatous components were encountered, probably arose in embryologic rests of renal tissue."}
{"id": "PMID:201363", "title": "Multiple childhood osteosarcomas in an American Indian family with erythroid macrocytosis and skeletal anomalies.", "content": "Three of nine children of possibly consanguineous American Indian parents developed typical osteosarcoma in a 2-year period. Etiologic investigations detected limb anomalies and elevated mean corpuscular volumes (98--109 micrometer3) in the surviving tumor patient, several of her sibs, and her father. Limb anomalies included simple clinodactyly with brachymesophalangy, absence of one digital ray of the foot, and bilateral radioulnar synostosis. The red cell macrocytosis was not accompanied by anemia or explained by the usual causes. No unusual environmental exposures were found and screening for possible oncogenic viruses by culture, electron microscopy, and serology was negative. All family members had elevated antibody titers to Epstein-Barr viral antigens. The proband and her father had excessive chromosomal breaks in the bone marrow. This unusual familial pattern of osseous malignancy and malformation and defective erythropoiesis, tentatively called OSLAM syndrome, may represent impaired regulation of bone development.", "contents": "Multiple childhood osteosarcomas in an American Indian family with erythroid macrocytosis and skeletal anomalies. Three of nine children of possibly consanguineous American Indian parents developed typical osteosarcoma in a 2-year period. Etiologic investigations detected limb anomalies and elevated mean corpuscular volumes (98--109 micrometer3) in the surviving tumor patient, several of her sibs, and her father. Limb anomalies included simple clinodactyly with brachymesophalangy, absence of one digital ray of the foot, and bilateral radioulnar synostosis. The red cell macrocytosis was not accompanied by anemia or explained by the usual causes. No unusual environmental exposures were found and screening for possible oncogenic viruses by culture, electron microscopy, and serology was negative. All family members had elevated antibody titers to Epstein-Barr viral antigens. The proband and her father had excessive chromosomal breaks in the bone marrow. This unusual familial pattern of osseous malignancy and malformation and defective erythropoiesis, tentatively called OSLAM syndrome, may represent impaired regulation of bone development."}
{"id": "PMID:201364", "title": "Central nervous system tumors in children.", "content": "Of 488 central nervous system neoplasms occurring in children over a 39-year period, 467 were intracranial and 21 were intraspinal. The most common intracranial neoplasms were astrocytoma (28%), medulloblastoma (25%), ependymal neoplasm (9%), craniopharyngioma (9%), and glioblastoma multiforme (9%). The median age at diagnosis was 6 years with a male-to-female ratio of 1.3:1. Overall mean survival was 53.4 months and varied greatly relative to the type of tumor and the location. Of the intraspinal neoplasms the most frequently noted were the astrocytoma (47%) and the ependymal neoplasma (24%). The median age at diagnosis was 10 years with a male-to-female ratio of 1:1. The average survival from diagnosis (54.1 months) was comparable to that of intracranial neoplasms. Detailed analyses of each histological type of tumor relative to age at diagnosis, sex, anatomical location and survival from diagnosis are reported for both intracranial and intraspinal neoplasms.", "contents": "Central nervous system tumors in children. Of 488 central nervous system neoplasms occurring in children over a 39-year period, 467 were intracranial and 21 were intraspinal. The most common intracranial neoplasms were astrocytoma (28%), medulloblastoma (25%), ependymal neoplasm (9%), craniopharyngioma (9%), and glioblastoma multiforme (9%). The median age at diagnosis was 6 years with a male-to-female ratio of 1.3:1. Overall mean survival was 53.4 months and varied greatly relative to the type of tumor and the location. Of the intraspinal neoplasms the most frequently noted were the astrocytoma (47%) and the ependymal neoplasma (24%). The median age at diagnosis was 10 years with a male-to-female ratio of 1:1. The average survival from diagnosis (54.1 months) was comparable to that of intracranial neoplasms. Detailed analyses of each histological type of tumor relative to age at diagnosis, sex, anatomical location and survival from diagnosis are reported for both intracranial and intraspinal neoplasms."}
{"id": "PMID:201365", "title": "Wilms' tumor in New York State: epidemiology and survivorship.", "content": "The outcomes during the period 1950--1972 were compared for Wilms' tumor patients in Erie County, New York (Buffalo and environs) and in a random selection of 23 counties having much smaller populations. For the Erie cohorts of 1967 to 1972 an 87 per cent 7-year survival rate was found as compared with a 50 per cent survival for the corresponding cohorts of the less populous couties. For the years 1960--1966 the 5-year survival rates were respectively 67 and 25 per cent and for the decade 1950--1959, 26 and 23 per cent. The principal conclusion is that within the last 15 years the Erie residents have fared better than residents of the smaller counties. The difference is attributed to the better treatment and care available at some of the hospitals in Buffalo. Data on incidence, age at diagnosis, male/female ratio, and laterality are presented.", "contents": "Wilms' tumor in New York State: epidemiology and survivorship. The outcomes during the period 1950--1972 were compared for Wilms' tumor patients in Erie County, New York (Buffalo and environs) and in a random selection of 23 counties having much smaller populations. For the Erie cohorts of 1967 to 1972 an 87 per cent 7-year survival rate was found as compared with a 50 per cent survival for the corresponding cohorts of the less populous couties. For the years 1960--1966 the 5-year survival rates were respectively 67 and 25 per cent and for the decade 1950--1959, 26 and 23 per cent. The principal conclusion is that within the last 15 years the Erie residents have fared better than residents of the smaller counties. The difference is attributed to the better treatment and care available at some of the hospitals in Buffalo. Data on incidence, age at diagnosis, male/female ratio, and laterality are presented."}
{"id": "PMID:201366", "title": "Changes in polyamine levels and protein synthesis rate during rat liver carcinogenesis induced by 4-dimethylaminoazobenzene.", "content": "The concentrations of putrescine, spermidine, and spermine in liver of rats fed on 4-dimethylaminoazobenzene and in the resultant hepatomas were found to be significantly higher than were those observed in normal liver from rats of the same strain, sex, and age. These modifications were due to the carcinogen and not to the special low-riboflavin diet used to obtain the carcinogenic effect of 4-dimethylaminoazobenzene. The first change observed during liver carcinogenesis was the early increase in the putrescine level, followed by an increase of spermidine and spermine, which reached maximum levels in growing hepatomas. A significant increase of urinary polyamines was also observed in tumor-bearing rats. Experiments on leucine incorporation into proteins of tissue slices, which were obtained from the same tissues on which polyamine determinations were carried out, showed that in rat liver carcinogenesis the rate of protein synthesis was well correlated with the polyamine levels. These results suggest that polyamines may play a role in the process of carcinogenesis and in tumor protein synthesis in vivo.", "contents": "Changes in polyamine levels and protein synthesis rate during rat liver carcinogenesis induced by 4-dimethylaminoazobenzene. The concentrations of putrescine, spermidine, and spermine in liver of rats fed on 4-dimethylaminoazobenzene and in the resultant hepatomas were found to be significantly higher than were those observed in normal liver from rats of the same strain, sex, and age. These modifications were due to the carcinogen and not to the special low-riboflavin diet used to obtain the carcinogenic effect of 4-dimethylaminoazobenzene. The first change observed during liver carcinogenesis was the early increase in the putrescine level, followed by an increase of spermidine and spermine, which reached maximum levels in growing hepatomas. A significant increase of urinary polyamines was also observed in tumor-bearing rats. Experiments on leucine incorporation into proteins of tissue slices, which were obtained from the same tissues on which polyamine determinations were carried out, showed that in rat liver carcinogenesis the rate of protein synthesis was well correlated with the polyamine levels. These results suggest that polyamines may play a role in the process of carcinogenesis and in tumor protein synthesis in vivo."}
{"id": "PMID:201367", "title": "Initial reaction of 3-ethyoxy-2-oxobutyraldehyde bis(thiosemicarbazonato) copper(II) with Ehrlich ascites tumor cells.", "content": "The antineoplastic agent, 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato) copper(II), undergoes a pseudo-first-order decomposition in the presence of viable Ehrlich ascites tumor cells. Physical and chemical methods show that the copper is reduced in this process, that thiols are involved in the reaction, and that the thiosemicarbazone ligand is displaced from the copper ion. The widespread distribution of the cell-bound copper suggests several modes of cytotoxicity.", "contents": "Initial reaction of 3-ethyoxy-2-oxobutyraldehyde bis(thiosemicarbazonato) copper(II) with Ehrlich ascites tumor cells. The antineoplastic agent, 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato) copper(II), undergoes a pseudo-first-order decomposition in the presence of viable Ehrlich ascites tumor cells. Physical and chemical methods show that the copper is reduced in this process, that thiols are involved in the reaction, and that the thiosemicarbazone ligand is displaced from the copper ion. The widespread distribution of the cell-bound copper suggests several modes of cytotoxicity."}
{"id": "PMID:201368", "title": "Mutagenicity of diallate, sulfallate, and triallate and relationship between structure and mutagenic effects of carbamates used widely in agriculture.", "content": "In an investigation of the mutagenic properties of 20 carbamate herbicides and fungicides by use of the Salmonella/microsome mutagenicity test as developed by Ames et al. (Mutation Res., 31: 347-364, 1975), we have found that three thiocarbamate compounds, diallate, sulfallate and triallate, are mutagenic in the presence of a liver microsomal fraction on strains TA1535 and TA100. This indicates that the metabolic products of these thiocarbamates are causing base-pair substitutions. Since the 2-chloro-allyl group is common to the three mutagenic compounds but is not common to the 17 nonmutagenic compounds, a metabolic derivative of this group is probably responsible for the mutagenic activity.", "contents": "Mutagenicity of diallate, sulfallate, and triallate and relationship between structure and mutagenic effects of carbamates used widely in agriculture. In an investigation of the mutagenic properties of 20 carbamate herbicides and fungicides by use of the Salmonella/microsome mutagenicity test as developed by Ames et al. (Mutation Res., 31: 347-364, 1975), we have found that three thiocarbamate compounds, diallate, sulfallate and triallate, are mutagenic in the presence of a liver microsomal fraction on strains TA1535 and TA100. This indicates that the metabolic products of these thiocarbamates are causing base-pair substitutions. Since the 2-chloro-allyl group is common to the three mutagenic compounds but is not common to the 17 nonmutagenic compounds, a metabolic derivative of this group is probably responsible for the mutagenic activity."}
{"id": "PMID:201369", "title": "Metabolic control of glycolysis in normal and tumor permeabilized cells.", "content": "Our previous reports have presented evidence suggesting the existence in tumor cells of a second control site of glycolysis of pyruvate kinase as a competition for adenosine diphosphate between this enzyme and mitochondria, which is responsible for the Crabtree effect. Now, by using cells partially permeabilized to nucleotides and phosphorylated substrates, we provide evidence supporting the existence in hepatocytes of a partial control by adenosine triphosphate at phosphofructokinase, which is followed by the total control by adenosine triphosphate at pyruvate kinase. The partial or nonoperation of this second site in Ehrlich ascites tumor cells appears to be the cause for the characteristic aerobic glycolysis, Crabtree effect, and low Pasteur effect of these cells.", "contents": "Metabolic control of glycolysis in normal and tumor permeabilized cells. Our previous reports have presented evidence suggesting the existence in tumor cells of a second control site of glycolysis of pyruvate kinase as a competition for adenosine diphosphate between this enzyme and mitochondria, which is responsible for the Crabtree effect. Now, by using cells partially permeabilized to nucleotides and phosphorylated substrates, we provide evidence supporting the existence in hepatocytes of a partial control by adenosine triphosphate at phosphofructokinase, which is followed by the total control by adenosine triphosphate at pyruvate kinase. The partial or nonoperation of this second site in Ehrlich ascites tumor cells appears to be the cause for the characteristic aerobic glycolysis, Crabtree effect, and low Pasteur effect of these cells."}
{"id": "PMID:201370", "title": "Ultrastructure of the thyroid gland in goitered coho salmon (Oncorhynchus kisutch).", "content": "Thyroid tissues in coho salmon (Oncorhynchus kisutch) goiters showed marked regional variation in structure and ultrastructure. For the most part the follicles were small, were composed of tall epithelial cells, and contained little or no colloid material. The follicle epithelial cells were essentially similar in fine structure to hyperactive thyroids in mammals and one type of follicle in congenital goiters in humans. A second type of follicle, present in human goiters, was not found in coho salmon. The follicle cells in coho salmon contained dense bodies similar to lysosomes in other species, together with larger organelles which could be colloid droplets. There was also an extensive system of dilated rough endoplasmic reticulum and large areas of Golgi membranes. A marked feature was the presence of homogeneous belectron-dense material in the intercellular spaces between adjacent follicle cells.", "contents": "Ultrastructure of the thyroid gland in goitered coho salmon (Oncorhynchus kisutch). Thyroid tissues in coho salmon (Oncorhynchus kisutch) goiters showed marked regional variation in structure and ultrastructure. For the most part the follicles were small, were composed of tall epithelial cells, and contained little or no colloid material. The follicle epithelial cells were essentially similar in fine structure to hyperactive thyroids in mammals and one type of follicle in congenital goiters in humans. A second type of follicle, present in human goiters, was not found in coho salmon. The follicle cells in coho salmon contained dense bodies similar to lysosomes in other species, together with larger organelles which could be colloid droplets. There was also an extensive system of dilated rough endoplasmic reticulum and large areas of Golgi membranes. A marked feature was the presence of homogeneous belectron-dense material in the intercellular spaces between adjacent follicle cells."}
{"id": "PMID:201371", "title": "Location of adult and fetal aldolases A, B, and C by immunoperoxidase technique in LF fast-growing rat hepatomas.", "content": "The resurgence of aldolase isozymes in cancerous tissues is a well-known but poorly understood phenomenon. This resurgence poses the problem of whether or not adult and fetal aldolase isozymes are produced by the same cells. For clarification of this question, the immunoperoxidase technique was used to locate aldolases A, B, and C in one type of fast-growing hepatoma, the LF hepatoma and, by comparison, in normal adult liver. Under optical microscopy, aldolases A and C were located in the cytoplasm of almost all of the cancerous cells. An isozyme antigenically identical with aldolase B was also demonstrated to be present in almost all of the cells, but the reaction indicating the presence of this isozyme was weaker. In normal adult liver, only aldolases A and B were demonstrated to be present in almost all the hepatocytes. Under electron microscopy in LF hepatoma, the three isozymes were found to be present mainly in the cytoplasm. These facts suggest that the three types of aldolase are very probably present in the same cells at the same time, and they provide indirect arguments leading us to think that the resurgence of fetal aldolase isozymes in cancer is not the consequence of cellular selection but is due to a disturbance at the gene control level.", "contents": "Location of adult and fetal aldolases A, B, and C by immunoperoxidase technique in LF fast-growing rat hepatomas. The resurgence of aldolase isozymes in cancerous tissues is a well-known but poorly understood phenomenon. This resurgence poses the problem of whether or not adult and fetal aldolase isozymes are produced by the same cells. For clarification of this question, the immunoperoxidase technique was used to locate aldolases A, B, and C in one type of fast-growing hepatoma, the LF hepatoma and, by comparison, in normal adult liver. Under optical microscopy, aldolases A and C were located in the cytoplasm of almost all of the cancerous cells. An isozyme antigenically identical with aldolase B was also demonstrated to be present in almost all of the cells, but the reaction indicating the presence of this isozyme was weaker. In normal adult liver, only aldolases A and B were demonstrated to be present in almost all the hepatocytes. Under electron microscopy in LF hepatoma, the three isozymes were found to be present mainly in the cytoplasm. These facts suggest that the three types of aldolase are very probably present in the same cells at the same time, and they provide indirect arguments leading us to think that the resurgence of fetal aldolase isozymes in cancer is not the consequence of cellular selection but is due to a disturbance at the gene control level."}
{"id": "PMID:201372", "title": "Patterns of spontaneous metastasis of transplantable hepatocellular carcinomas.", "content": "A number of transplantable rat hepatocellular carcinomas of varied phenotype were examined for their ability to metastasize. A striking diversity of pattern was observed, ranging from presentation in almost every organ to none at all. No relationship between metastatic capability and growth rate, tumor size, chromosome composition, or other functional characteristics was noted. Interestingly, several of the tumors demonstrated a lymphatic to vascular route of spread, very similar to that of human tumors.", "contents": "Patterns of spontaneous metastasis of transplantable hepatocellular carcinomas. A number of transplantable rat hepatocellular carcinomas of varied phenotype were examined for their ability to metastasize. A striking diversity of pattern was observed, ranging from presentation in almost every organ to none at all. No relationship between metastatic capability and growth rate, tumor size, chromosome composition, or other functional characteristics was noted. Interestingly, several of the tumors demonstrated a lymphatic to vascular route of spread, very similar to that of human tumors."}
{"id": "PMID:201373", "title": "Turnover of cellular carbohydrates in normal and Rous sarcoma virus-transformed cells.", "content": "We have analyzed the distribution of glucosamine-labeled polymers on the cell surface, in the growth medium, and inside the cell and the net turnover of these polymers during the process of malignant transformation of chick embryo fibroblasts by Rous sarcoma virus. The distribution of label and the turnover kinetics for hyaluronic acid, total glycoproteins, and chondroitins were found to be identical in both normal and transforming cultures. We conclude that nonspecific degradative processes are probably not involved in causing transformation-related alterations in cell surface carbohydrates, althougn degradation of specific macromolecules is not excluded.", "contents": "Turnover of cellular carbohydrates in normal and Rous sarcoma virus-transformed cells. We have analyzed the distribution of glucosamine-labeled polymers on the cell surface, in the growth medium, and inside the cell and the net turnover of these polymers during the process of malignant transformation of chick embryo fibroblasts by Rous sarcoma virus. The distribution of label and the turnover kinetics for hyaluronic acid, total glycoproteins, and chondroitins were found to be identical in both normal and transforming cultures. We conclude that nonspecific degradative processes are probably not involved in causing transformation-related alterations in cell surface carbohydrates, althougn degradation of specific macromolecules is not excluded."}
{"id": "PMID:201374", "title": "Immunotherapy of established micrometastases with Bacillus Calmette-Gu\u00e9rin tumor cell vaccine.", "content": "We evaluated the use of Bacillus Calmette-Gu\u00e9rin admixed with tumor cells as a vaccine to induce systemic tumor immunity for therapy of subclinical (micrometastatic) disease. In several experiments inbred strain 2 guinea pigs were given i.v. injections of either 10(4), 10(5), or 10(6) syngeneic L10 hepatocarcinoma cells, and initial vaccinations were administered either 1 or 4 days after tumor inocluation. Variables in vaccine preparation, such as ratio of viable Bacillus Calmette-Gu\u00e9rin organisms to tumor cells, procedures for freezing the tumor cells, X-ray treatment of tumor cells, and vaccination regimen were evaluated. The studies demonstrated that under defined conditions nontumorigenic vaccines of Bacillus Calmette-Gu\u00e9rin and tumor cells can cure the majority of animals of otherwise lethal visceral micrometastases.", "contents": "Immunotherapy of established micrometastases with Bacillus Calmette-Gu\u00e9rin tumor cell vaccine. We evaluated the use of Bacillus Calmette-Gu\u00e9rin admixed with tumor cells as a vaccine to induce systemic tumor immunity for therapy of subclinical (micrometastatic) disease. In several experiments inbred strain 2 guinea pigs were given i.v. injections of either 10(4), 10(5), or 10(6) syngeneic L10 hepatocarcinoma cells, and initial vaccinations were administered either 1 or 4 days after tumor inocluation. Variables in vaccine preparation, such as ratio of viable Bacillus Calmette-Gu\u00e9rin organisms to tumor cells, procedures for freezing the tumor cells, X-ray treatment of tumor cells, and vaccination regimen were evaluated. The studies demonstrated that under defined conditions nontumorigenic vaccines of Bacillus Calmette-Gu\u00e9rin and tumor cells can cure the majority of animals of otherwise lethal visceral micrometastases."}
{"id": "PMID:201375", "title": "Protection against MOPC-315 plasmacytoma by immunization with C-type particle preparations.", "content": "Mice were given injections of C-type particles extracted from the ascitic fluid of plasmacytoma-bearing mice. These particles, extracted from MOPC-315 tumor-bearing mice and injected into BALB/c mice, protected them against challenge with MOPC-315 tumor cells. The protection was dependent upon tumor cell dose; 66% survival was observed with a lethal dose of tumor cells. No protection was observed against challenge with another plasmacytoma (S13). Attempts to protect mice against S-13 plasmacytoma by immunizing them with C-type particles originating from S-13 tumor-bearing mice were unsuccessful.", "contents": "Protection against MOPC-315 plasmacytoma by immunization with C-type particle preparations. Mice were given injections of C-type particles extracted from the ascitic fluid of plasmacytoma-bearing mice. These particles, extracted from MOPC-315 tumor-bearing mice and injected into BALB/c mice, protected them against challenge with MOPC-315 tumor cells. The protection was dependent upon tumor cell dose; 66% survival was observed with a lethal dose of tumor cells. No protection was observed against challenge with another plasmacytoma (S13). Attempts to protect mice against S-13 plasmacytoma by immunizing them with C-type particles originating from S-13 tumor-bearing mice were unsuccessful."}
{"id": "PMID:201376", "title": "Inhibitory effect of hypothalamic lesions on liver tumor induction by N-2-fluorenylacetamide in male rats.", "content": "Bilateral electrolytic lesions were placed in the median eminence area of the hypothalamus in 12-week-old male Wistar rats. Sham-operated and untreated control rats were also included. Two weeks later, one-half of them were given 0.03% N-2-fluorenylacetamide incorporated into the diet for 16 weeks with adequate resting periods in between. The animals were killed 34 weeks after the last carcinogen feeding. The results show that lesions in the hypothalamus effectively inhibited liver tumor formation (0 of 16, 0%). In contrast, the incidence of hepatocellular carcinomas in sham-operated rats was 38.5% (5 of 13), and that of untreated controls was 42.9% (6 oactive thyroid glands, and shorter nasoanal lengths were observed in rats with lesions in the hypothalamus irrespective of carcinogen treatment. It is apparent from these data that lesions in the median eminence area of the hypothalamus inhibit the induction of liver carcinogenesis with N-2-fluorenylacetamide in male rats.", "contents": "Inhibitory effect of hypothalamic lesions on liver tumor induction by N-2-fluorenylacetamide in male rats. Bilateral electrolytic lesions were placed in the median eminence area of the hypothalamus in 12-week-old male Wistar rats. Sham-operated and untreated control rats were also included. Two weeks later, one-half of them were given 0.03% N-2-fluorenylacetamide incorporated into the diet for 16 weeks with adequate resting periods in between. The animals were killed 34 weeks after the last carcinogen feeding. The results show that lesions in the hypothalamus effectively inhibited liver tumor formation (0 of 16, 0%). In contrast, the incidence of hepatocellular carcinomas in sham-operated rats was 38.5% (5 of 13), and that of untreated controls was 42.9% (6 oactive thyroid glands, and shorter nasoanal lengths were observed in rats with lesions in the hypothalamus irrespective of carcinogen treatment. It is apparent from these data that lesions in the median eminence area of the hypothalamus inhibit the induction of liver carcinogenesis with N-2-fluorenylacetamide in male rats."}
{"id": "PMID:201377", "title": "General immunocompetence of rats bearing avian sarcoma virus-induced intracranial tumors.", "content": "The mitogenic responsiveness of spleen cells obtained from avian sarcoma virus-inoculated Fischer 344 rats was studied. Sixty % of the rats had astrocytomas, 13% had sarcomas, 7% had mixed gliosarcomas, and 20% had no evidence of tumors. Only spleen cells from rats bearing astrocytomas had significantly diminished responses to phytohemagglutinin and concanavalin A (Con A) when compared to control responses. The decreased responsiveness observed with phytohemagglutinin was limited to the optimal concentration range (10 and 20 microgram) while a broader concentration of Con A (0.01 to 50 microgram) induced significant suppression. Moreover, a more profound immunosuppression was observed with Con A. The results also demonstrated that spleen cells from rats with the largest astrocytomas exhibited the greatest suppression. From the results of this study, it appears the avian sarcoma virus-induced astrocytoma in rats is an immunological parallel of the human disease based on the loss of general immunological competence as assessed by responsiveness of lymphocytes to phytohemagglutinin and Con A.", "contents": "General immunocompetence of rats bearing avian sarcoma virus-induced intracranial tumors. The mitogenic responsiveness of spleen cells obtained from avian sarcoma virus-inoculated Fischer 344 rats was studied. Sixty % of the rats had astrocytomas, 13% had sarcomas, 7% had mixed gliosarcomas, and 20% had no evidence of tumors. Only spleen cells from rats bearing astrocytomas had significantly diminished responses to phytohemagglutinin and concanavalin A (Con A) when compared to control responses. The decreased responsiveness observed with phytohemagglutinin was limited to the optimal concentration range (10 and 20 microgram) while a broader concentration of Con A (0.01 to 50 microgram) induced significant suppression. Moreover, a more profound immunosuppression was observed with Con A. The results also demonstrated that spleen cells from rats with the largest astrocytomas exhibited the greatest suppression. From the results of this study, it appears the avian sarcoma virus-induced astrocytoma in rats is an immunological parallel of the human disease based on the loss of general immunological competence as assessed by responsiveness of lymphocytes to phytohemagglutinin and Con A."}
{"id": "PMID:201378", "title": "Localization of meso-tetra(p-sulfophenyl)porphine in murine sarcoma virus-induced tumor-bearing mice.", "content": "meso-Tetra(p-sulfophenyl)porphine (TPPS4) has been found to accumulate in the tumors of mice bearing a murine sarcoma virus-induced rhabdomyosarcoma to a greater degree than in all other tissues except for the kidney. Tumor to tissue ratios of from 3:1 (tumor to liver) to 9:1 (tumor to muscle) were observed. The uptake of TPPS4 was found to be dose dependent, and the highest tumor to tissue ratios were found 96 hours after injection. The water-soluble TPPS4 appears to be cleared through the kidneys and absolute concentrations there are reduced with increasing time after injection. These data are compared with previous studies on TPPS4 localization in Walker 256 carcinosarcoma-bearing mice. In view of this localizing ability and its relative lack of toxicity, TPPS4 seems to represent an ideal candidate for a tumor-localizing agent if high levels of the porphyrin in the kidneys can be reversed.", "contents": "Localization of meso-tetra(p-sulfophenyl)porphine in murine sarcoma virus-induced tumor-bearing mice. meso-Tetra(p-sulfophenyl)porphine (TPPS4) has been found to accumulate in the tumors of mice bearing a murine sarcoma virus-induced rhabdomyosarcoma to a greater degree than in all other tissues except for the kidney. Tumor to tissue ratios of from 3:1 (tumor to liver) to 9:1 (tumor to muscle) were observed. The uptake of TPPS4 was found to be dose dependent, and the highest tumor to tissue ratios were found 96 hours after injection. The water-soluble TPPS4 appears to be cleared through the kidneys and absolute concentrations there are reduced with increasing time after injection. These data are compared with previous studies on TPPS4 localization in Walker 256 carcinosarcoma-bearing mice. In view of this localizing ability and its relative lack of toxicity, TPPS4 seems to represent an ideal candidate for a tumor-localizing agent if high levels of the porphyrin in the kidneys can be reversed."}
{"id": "PMID:201381", "title": "Scintigraphic visualization of myocardial infarcts in baboons using thallium-201 and  technetium-99m pyrophosphate.", "content": "4 baboons with myocardial infarcts were evaluated using thallium-201 for myocardial imaging and 99Tcm pyrophosphate for infarct visualization. Scintiphotographic findings were compared with the size of myocardial infarcts calculated from measurements of the activity of MB isoenzymes of creatine kinase (CK-MB) in serum and in the myocardium at autopsy, as described by Sobel's method. Lack of thallium-201 accumulation was noted in left ventricular infarcts of 3 of the 4 baboons. These same areas localized 99Tcm pyrophosphate administered 24--30 h after infarction.", "contents": "Scintigraphic visualization of myocardial infarcts in baboons using thallium-201 and  technetium-99m pyrophosphate. 4 baboons with myocardial infarcts were evaluated using thallium-201 for myocardial imaging and 99Tcm pyrophosphate for infarct visualization. Scintiphotographic findings were compared with the size of myocardial infarcts calculated from measurements of the activity of MB isoenzymes of creatine kinase (CK-MB) in serum and in the myocardium at autopsy, as described by Sobel's method. Lack of thallium-201 accumulation was noted in left ventricular infarcts of 3 of the 4 baboons. These same areas localized 99Tcm pyrophosphate administered 24--30 h after infarction."}
{"id": "PMID:201382", "title": "The effect of diet on the ultrastructure of the mid-gut cells of Nasonia vitripennis (Walk.) (Insecta: Hymenoptera) at various ages.", "content": "The ultrastructure of mid-gut cells of female Nasonia fed on a diet of 10% sterile sucrose is described. There are extensive alterations in cell organelles, particularly the mitochondria, rough endoplasmic reticulum (R.E.R.) and lipid inclusions, when compared to similar insects fed a normal diet of dipteran pupae. A proportion of the mitochondria found in the apical cell region are enlarged in size and contain electron-dense granules. The remaining mitochondria are smaller, but also contain electron-dense granules. Cytochrome-c oxidase activity appears to be absent from the enlarged mitochondria. The R.E.R. appears reduced in many cells of the 1 day old, sugar-fed insects, however, this component fluctuates throughout the remaining life span. The lipid inclusions prominent in the 1 day old, pupae-fed insects are not present in sucrose-fed females of the same age, but lipid deposition was recorded later in the life span. There are many large residual bodies and cytolysosomes present in the old, sugar-fed insects. These changes in ultrastructure are discussed in relation to diet and longevity.", "contents": "The effect of diet on the ultrastructure of the mid-gut cells of Nasonia vitripennis (Walk.) (Insecta: Hymenoptera) at various ages. The ultrastructure of mid-gut cells of female Nasonia fed on a diet of 10% sterile sucrose is described. There are extensive alterations in cell organelles, particularly the mitochondria, rough endoplasmic reticulum (R.E.R.) and lipid inclusions, when compared to similar insects fed a normal diet of dipteran pupae. A proportion of the mitochondria found in the apical cell region are enlarged in size and contain electron-dense granules. The remaining mitochondria are smaller, but also contain electron-dense granules. Cytochrome-c oxidase activity appears to be absent from the enlarged mitochondria. The R.E.R. appears reduced in many cells of the 1 day old, sugar-fed insects, however, this component fluctuates throughout the remaining life span. The lipid inclusions prominent in the 1 day old, pupae-fed insects are not present in sucrose-fed females of the same age, but lipid deposition was recorded later in the life span. There are many large residual bodies and cytolysosomes present in the old, sugar-fed insects. These changes in ultrastructure are discussed in relation to diet and longevity."}
{"id": "PMID:201383", "title": "Intramitochondrial bodies in bovine adrenocortical cells.", "content": "Electron dense, homogeneous, mostly round intramitochondrial bodies were found in bovine adrenal glands, predominantly in the zona glomerulosa. The histochemical results obtained suggest that these bodies might contain a considerable amount of protein, although the possibility that substances other than proteins are contained in these bodies cannot be completely ruled out. The physiological significance of the intramitochondrial bodies remains unclear.", "contents": "Intramitochondrial bodies in bovine adrenocortical cells. Electron dense, homogeneous, mostly round intramitochondrial bodies were found in bovine adrenal glands, predominantly in the zona glomerulosa. The histochemical results obtained suggest that these bodies might contain a considerable amount of protein, although the possibility that substances other than proteins are contained in these bodies cannot be completely ruled out. The physiological significance of the intramitochondrial bodies remains unclear."}
{"id": "PMID:201385", "title": "The mechanisms of hepatic and renal metallothionein biosynthesis in cadmium-exposed rats.", "content": "The mechanisms by which cadmium (Cd) stimulates the synthesis of hepatic and renal metallothionein were investigated in rats. In the liver the incorporation of 35S and 14C labels from cystine showed a lag period of about 2 h and maximum incorporation into metallothionein took place 8--12 h after injection of 30 mumol CdCl2/kg. The incorporation of the labels into renal metallothionein was faster than into the hepatic protein; the lag period was less than 1 h and maximum incorporation occurred 4--5 h after the Cd injection. Cycloheximide inhibited the amino acid incorporation into both hepatic and renal metallothionein. Actinomycin D treatment, however, inhibited hepatic metallothionein synthesis only. These results suggested that at the dose level employed Cd regulated the biosynthesis of metallothionein in the liver at the transcriptional level and in the kidney at the translational level.", "contents": "The mechanisms of hepatic and renal metallothionein biosynthesis in cadmium-exposed rats. The mechanisms by which cadmium (Cd) stimulates the synthesis of hepatic and renal metallothionein were investigated in rats. In the liver the incorporation of 35S and 14C labels from cystine showed a lag period of about 2 h and maximum incorporation into metallothionein took place 8--12 h after injection of 30 mumol CdCl2/kg. The incorporation of the labels into renal metallothionein was faster than into the hepatic protein; the lag period was less than 1 h and maximum incorporation occurred 4--5 h after the Cd injection. Cycloheximide inhibited the amino acid incorporation into both hepatic and renal metallothionein. Actinomycin D treatment, however, inhibited hepatic metallothionein synthesis only. These results suggested that at the dose level employed Cd regulated the biosynthesis of metallothionein in the liver at the transcriptional level and in the kidney at the translational level."}
{"id": "PMID:201389", "title": "Poxvirus in West African nonhuman primates: serological survey results.", "content": "Ten species of nonhuman primates in West African habitat were analysed for variolavaccinia subgroup haemagglutination-inhibition (HI) and neutralization antibodies. The animals were taken in 27 different sampling zones in parts of the Ivory Coast, Mali, and Upper Volta. Of the 195 tested, 15 (8%) had elevated HI antibodies after nonspecific reactions were reduced with potassium periodate pretreatment. Positive neutralization antibodies were found in 21% (44 of 206). Antibodies were detected in serum from monkeys living near two areas where monkeypox cases in humans had occurred. Four samples were tested for monkeypox specific antibodies using an indirect immunofluorescent test; 3 were positive. Despite the prevalence of poxvirus antibodies in monkeys (and other animals) in West Africa, smallpox eradication has been maintained in the area since 1970; thus, animal reservoirs of poxvirus appear to pose no threat to the worldwide smallpox eradication programme.", "contents": "Poxvirus in West African nonhuman primates: serological survey results. Ten species of nonhuman primates in West African habitat were analysed for variolavaccinia subgroup haemagglutination-inhibition (HI) and neutralization antibodies. The animals were taken in 27 different sampling zones in parts of the Ivory Coast, Mali, and Upper Volta. Of the 195 tested, 15 (8%) had elevated HI antibodies after nonspecific reactions were reduced with potassium periodate pretreatment. Positive neutralization antibodies were found in 21% (44 of 206). Antibodies were detected in serum from monkeys living near two areas where monkeypox cases in humans had occurred. Four samples were tested for monkeypox specific antibodies using an indirect immunofluorescent test; 3 were positive. Despite the prevalence of poxvirus antibodies in monkeys (and other animals) in West Africa, smallpox eradication has been maintained in the area since 1970; thus, animal reservoirs of poxvirus appear to pose no threat to the worldwide smallpox eradication programme."}
{"id": "PMID:201390", "title": "Differentiation of variola, monkeypox, and vaccinia antisera by radioimmunoassay.", "content": "Poxvirus antisera adsorbed with \"homologous\" and \"heterologous\" poxvirus-infected chorioallantoic membranes (CAM) were differentiated by solid-phase radioimmunoassay (RIA). Mixtures of the antiserum dilutions and infected CAM were added directly (without centrifugation) to poxvirus-infected CAM antigens affixed to wells of microtitration plates. The affixed antigens combined with unadsorbed antibodies, and the cross-reactive antigen-antibody complexes were removed by washing. The results showed that adsorption of an antiserum with variola-, vaccinia-, or uninfected-CAM antigen and subsequent reaction of each in RIA with monkeypox- and uninfected-CAM antigens allowed the identification of antivariola, antivaccinia, or antimonkeypox sera.", "contents": "Differentiation of variola, monkeypox, and vaccinia antisera by radioimmunoassay. Poxvirus antisera adsorbed with \"homologous\" and \"heterologous\" poxvirus-infected chorioallantoic membranes (CAM) were differentiated by solid-phase radioimmunoassay (RIA). Mixtures of the antiserum dilutions and infected CAM were added directly (without centrifugation) to poxvirus-infected CAM antigens affixed to wells of microtitration plates. The affixed antigens combined with unadsorbed antibodies, and the cross-reactive antigen-antibody complexes were removed by washing. The results showed that adsorption of an antiserum with variola-, vaccinia-, or uninfected-CAM antigen and subsequent reaction of each in RIA with monkeypox- and uninfected-CAM antigens allowed the identification of antivariola, antivaccinia, or antimonkeypox sera."}
{"id": "PMID:201391", "title": "The viral etiology of acute respiratory infections in children in Uganda.", "content": "The role of viruses in respiratory diseases of young children in Uganda was studied. A viral etiology was established in 36% of the infections investigated. The most important pathogens were found to be respiratory syncytial virus and parainfluenza viruses, which were responsible for 26% of infections investigated. They caused both upper and lower respiratory tract diseases. There was little or no seasonal variation in the etiology of these infections. Adenoviruses were found to be less important and were etiologically related to only 4% of respiratory disease cases. Influenza viruses and enteroviruses were also found to be associated with respiratory infections. However, they were less frequent and their role was insignificant. The role of multiple virus infections was also insignificant.", "contents": "The viral etiology of acute respiratory infections in children in Uganda. The role of viruses in respiratory diseases of young children in Uganda was studied. A viral etiology was established in 36% of the infections investigated. The most important pathogens were found to be respiratory syncytial virus and parainfluenza viruses, which were responsible for 26% of infections investigated. They caused both upper and lower respiratory tract diseases. There was little or no seasonal variation in the etiology of these infections. Adenoviruses were found to be less important and were etiologically related to only 4% of respiratory disease cases. Influenza viruses and enteroviruses were also found to be associated with respiratory infections. However, they were less frequent and their role was insignificant. The role of multiple virus infections was also insignificant."}
{"id": "PMID:201394", "title": "Buffer-exchange column for rapid separation of carcinoembryonic antigen from perchloric acid.", "content": "A Sephadex G-50 medium (Pharmacia) buffer-exchange column has been developed for rapidly changing the medium for carcinoembryonic antigen from perchloric acid to acetate buffer. Analytical recovery of the extracted antigen exceeded 95%. Plasma for analysis can be so prepared and samples ready for analysis within an hour. The technique also results in uniform assay volume, thus eliminating this variable from the assay.", "contents": "Buffer-exchange column for rapid separation of carcinoembryonic antigen from perchloric acid. A Sephadex G-50 medium (Pharmacia) buffer-exchange column has been developed for rapidly changing the medium for carcinoembryonic antigen from perchloric acid to acetate buffer. Analytical recovery of the extracted antigen exceeded 95%. Plasma for analysis can be so prepared and samples ready for analysis within an hour. The technique also results in uniform assay volume, thus eliminating this variable from the assay."}
{"id": "PMID:201395", "title": "Lipoprotein cholesterol in the serum of children, as determined independently by two different methods.", "content": "We separately evaluated split specimens of serum for lipoprotein cholesterol in 38 five- to 14-year-old children, by the heparin/Ca2+ precipitation method and the ultracentrifugation/dextran sulfate precipitation method. Statistical analysis of the results indicated an excellent agreement (especially in beta- and alpha-lipoprotein cholesterol values) between results by the two methods. The percentage of alpha-lipoprotein cholesterol (mean +/- SD: 38.6 +/- 5.0) in children further confirmed the earlier observations that cholesterol derived from alpha-lipoprotein in children constitutes a relatively greater part of the serum total cholesterol than is true of adults.", "contents": "Lipoprotein cholesterol in the serum of children, as determined independently by two different methods. We separately evaluated split specimens of serum for lipoprotein cholesterol in 38 five- to 14-year-old children, by the heparin/Ca2+ precipitation method and the ultracentrifugation/dextran sulfate precipitation method. Statistical analysis of the results indicated an excellent agreement (especially in beta- and alpha-lipoprotein cholesterol values) between results by the two methods. The percentage of alpha-lipoprotein cholesterol (mean +/- SD: 38.6 +/- 5.0) in children further confirmed the earlier observations that cholesterol derived from alpha-lipoprotein in children constitutes a relatively greater part of the serum total cholesterol than is true of adults."}
{"id": "PMID:201396", "title": "Use of the Du Pont aca to measure cholesterol in high-density lipoprotein fractions prepared by the heparin/Mn2+ precipitation method.", "content": "The enzymatic cholesterol method used with the Du Pont aca has been modified to provide a reliable measurement of high-density lipoprotein cholesterol in serum after heparin/Mn2+ precipitation of the low- and very-low-density lipoproteins. Interference by Mn2+, equivalent to about 90 mg of cholesterol per liter, is decreased to less than 40 mg of cholesterol per liter by the presence of ethylenediaminetetraacetate (8 mmol/liter) in the diluent; the residual effect of Mn2+ is compensated by calibrating the aca with standards containing Mn2+ and heparin. With an 80-microliter sample, the sensitivity is 236 muA/mg per liter and linearity ranges from 50 to 1500 mg/liter. Average analytical recovery of cholesterol added to the high-density lipoprotein fraction was 103%. Diluted fractions give the expected results. Between-run reproducibility (CV) is 1.3 and 1.6% at 463 and 554 mg/liter. Correlation with the Lipid Research Clinics' procedure (25 samples) gave a regression line of y(aca) = 1.039x- 15, and a correlation coefficient of 0.997.", "contents": "Use of the Du Pont aca to measure cholesterol in high-density lipoprotein fractions prepared by the heparin/Mn2+ precipitation method. The enzymatic cholesterol method used with the Du Pont aca has been modified to provide a reliable measurement of high-density lipoprotein cholesterol in serum after heparin/Mn2+ precipitation of the low- and very-low-density lipoproteins. Interference by Mn2+, equivalent to about 90 mg of cholesterol per liter, is decreased to less than 40 mg of cholesterol per liter by the presence of ethylenediaminetetraacetate (8 mmol/liter) in the diluent; the residual effect of Mn2+ is compensated by calibrating the aca with standards containing Mn2+ and heparin. With an 80-microliter sample, the sensitivity is 236 muA/mg per liter and linearity ranges from 50 to 1500 mg/liter. Average analytical recovery of cholesterol added to the high-density lipoprotein fraction was 103%. Diluted fractions give the expected results. Between-run reproducibility (CV) is 1.3 and 1.6% at 463 and 554 mg/liter. Correlation with the Lipid Research Clinics' procedure (25 samples) gave a regression line of y(aca) = 1.039x- 15, and a correlation coefficient of 0.997."}
{"id": "PMID:201398", "title": "Serum and lipoprotein apolipoprotein B levels in normal subjects and patients with hyperlipoproteinaemia.", "content": "Apolipoprotein B (apo B) levels were measured by radioimmunoassay in the serum and lipoproteins from normal subjects and patients with hyperlipoproteinaemia. The total serum apo B concentration in normal subjects was 0.91 +/- 0.16 g/l (mean +/- S.D.); in type IIa hyperlipoproteinaemia it was 2.24 +/- 0.61 g/l; in type IIb, 3.05 +/- 1.24 g/l; in type IV, 2.24 +/- 0.99 g/l; and in type V, 1.30 +/- 0.16 g/l. In normal subjects 5.6 +/- 2.1% (mean +/- S.D.) of total apo B was present in very low density lipoproteins (VLDL) and 93 +/- 9% in low density lipoproteins (LDL). Corresponding values for type IIa were 3.8 +/- 1.9% and 93 +/- 3%, for type IIb, 9.9 +/- 7.5% and 91 +/- 1%, for type IV, 16.9 +/- 9.5% and 81 +/- 9%, and for type V, 38.4 +/- 11.0% and 52 +/- 8%. The ratio of cholesterol to apo B in serum was decreased in types IIa, IIb and IV, and increased in type V whereas the ratio of triglyceride to apo B in serum was decreased in type IIa, normal in type IIb and increased in types IV and V. The ratio of cholesterol to apo B in VLDL was increased in types IIa, IIb and V, but normal in type IV, whereas in LDL, this ratio was normal in types IIa and V but reduced in types IIb and IV. The ratio of triglycerides to apo B in VLDL was normal in types IIa, IIb and IV but raised in type V. In LDL, this ratio was increased in types IIb and IV but normal in types IIa and V.", "contents": "Serum and lipoprotein apolipoprotein B levels in normal subjects and patients with hyperlipoproteinaemia. Apolipoprotein B (apo B) levels were measured by radioimmunoassay in the serum and lipoproteins from normal subjects and patients with hyperlipoproteinaemia. The total serum apo B concentration in normal subjects was 0.91 +/- 0.16 g/l (mean +/- S.D.); in type IIa hyperlipoproteinaemia it was 2.24 +/- 0.61 g/l; in type IIb, 3.05 +/- 1.24 g/l; in type IV, 2.24 +/- 0.99 g/l; and in type V, 1.30 +/- 0.16 g/l. In normal subjects 5.6 +/- 2.1% (mean +/- S.D.) of total apo B was present in very low density lipoproteins (VLDL) and 93 +/- 9% in low density lipoproteins (LDL). Corresponding values for type IIa were 3.8 +/- 1.9% and 93 +/- 3%, for type IIb, 9.9 +/- 7.5% and 91 +/- 1%, for type IV, 16.9 +/- 9.5% and 81 +/- 9%, and for type V, 38.4 +/- 11.0% and 52 +/- 8%. The ratio of cholesterol to apo B in serum was decreased in types IIa, IIb and IV, and increased in type V whereas the ratio of triglyceride to apo B in serum was decreased in type IIa, normal in type IIb and increased in types IV and V. The ratio of cholesterol to apo B in VLDL was increased in types IIa, IIb and V, but normal in type IV, whereas in LDL, this ratio was normal in types IIa and V but reduced in types IIb and IV. The ratio of triglycerides to apo B in VLDL was normal in types IIa, IIb and IV but raised in type V. In LDL, this ratio was increased in types IIb and IV but normal in types IIa and V."}
{"id": "PMID:201399", "title": "Collagenase activity of rat kidney with immune complex glomerulonephritis.", "content": "By means of a biological assay the collagenolytic activity of kidneys from rats with experimental immune complex glomerulonephritis and control animals was tested. We detected collagenolysis in both panels but found quantitative differences in the collagenase activity. The enzymatic collagenolysis was significantly increased (P less than 0.001) in the nephritic kidneys. From the fact that the chelating agent EDTA inhibited potentially the released enzyme it can be concluded that the origin is the polymorphonuclear granules.", "contents": "Collagenase activity of rat kidney with immune complex glomerulonephritis. By means of a biological assay the collagenolytic activity of kidneys from rats with experimental immune complex glomerulonephritis and control animals was tested. We detected collagenolysis in both panels but found quantitative differences in the collagenase activity. The enzymatic collagenolysis was significantly increased (P less than 0.001) in the nephritic kidneys. From the fact that the chelating agent EDTA inhibited potentially the released enzyme it can be concluded that the origin is the polymorphonuclear granules."}
{"id": "PMID:201400", "title": "Changes in rat serum lipoproteins following ligation of the bile duct.", "content": "Lipoproteins in the serum of normal and of cholestatic rats have been studied by crossed immunoelectrophoresis coupled with separations by rate and isopycnic density gradient centrifugation and by gel exclusion chromatography. Normal rat serum contained distinct lipoprotein species closely analogous to human VLDL, LDL, HDL2 and HDL3. Three days after ligation of the common bile duct, there were major changes in the lipoproteins of rat serum. The amounts of VLDL, LDL and of a minor HDL component were elevated and several novel types of lipoprotein were detected. Three of these could be identified as the characteristic lipoprotein of cholestasis, LP-X, as an enlarged and modified HDL and as a lipoprotein of density 1.055 g/ml intermediate in size between LDL and VLDL. Some unusually small VLDL particles were also detected. It is concluded that the changes in rat serum lipoproteins following ligation of the common bile duct are very similar to the changes observed in cholestatic disease in human patients.", "contents": "Changes in rat serum lipoproteins following ligation of the bile duct. Lipoproteins in the serum of normal and of cholestatic rats have been studied by crossed immunoelectrophoresis coupled with separations by rate and isopycnic density gradient centrifugation and by gel exclusion chromatography. Normal rat serum contained distinct lipoprotein species closely analogous to human VLDL, LDL, HDL2 and HDL3. Three days after ligation of the common bile duct, there were major changes in the lipoproteins of rat serum. The amounts of VLDL, LDL and of a minor HDL component were elevated and several novel types of lipoprotein were detected. Three of these could be identified as the characteristic lipoprotein of cholestasis, LP-X, as an enlarged and modified HDL and as a lipoprotein of density 1.055 g/ml intermediate in size between LDL and VLDL. Some unusually small VLDL particles were also detected. It is concluded that the changes in rat serum lipoproteins following ligation of the common bile duct are very similar to the changes observed in cholestatic disease in human patients."}
{"id": "PMID:201401", "title": "The mechanism of action of polypeptide hormones with special reference to insulin's action on glucose transport.", "content": "In the last decade substantial progress has been made in elucidation of the mechanisms of action of polypeptide hormones. For instance, it has become clear that these hormones bind to their target cells and that at least one component of the binding is saturable. This phenomenon, which is usually called receptor binding, is believed to be the first and necessary event in the chain of processes which lead to effects of the hormone on their target cells. Receptor binding is just one aspect of the mechanism of action of polypeptide hormones. The properties of binding differ from hormone to hormone as do the events after binding. The purpose of this communication is to describe some aspects of the mechanism of insulin action on transmembrane glucose transport, and to disucss general aspects of polypeptide hormone action in relation to the specific findings with insulin. Comprehensive reviews on polypeptide hormone receptors have been published recently (Freychet, 1976; Kahn, 1976).", "contents": "The mechanism of action of polypeptide hormones with special reference to insulin's action on glucose transport. In the last decade substantial progress has been made in elucidation of the mechanisms of action of polypeptide hormones. For instance, it has become clear that these hormones bind to their target cells and that at least one component of the binding is saturable. This phenomenon, which is usually called receptor binding, is believed to be the first and necessary event in the chain of processes which lead to effects of the hormone on their target cells. Receptor binding is just one aspect of the mechanism of action of polypeptide hormones. The properties of binding differ from hormone to hormone as do the events after binding. The purpose of this communication is to describe some aspects of the mechanism of insulin action on transmembrane glucose transport, and to disucss general aspects of polypeptide hormone action in relation to the specific findings with insulin. Comprehensive reviews on polypeptide hormone receptors have been published recently (Freychet, 1976; Kahn, 1976)."}
{"id": "PMID:201402", "title": "Prolactin secretion in girls with isolated gonadotrophin deficiency.", "content": "Plasma prolactin, basal levels and the response to an i.v. injection of TRH (100 microgram/m2) was determined in five girls with isolated gonadotrophin deficiency of hypothalamic origin before and after at least 3 months cyclic replacement therapy with conjugated oestrogens (1.25 mg/day). The basal plasma prolactin levels were similar during both tests, however, during oestrogen therapy the mean peak response to TRH almost doubled and the sum of all the values obtained (basal, +15, +30 and +60 min) was significantly higher. It is of note that even upon prolonged oestrogen deprivation the releasable prolactin response to TRH was adequate.", "contents": "Prolactin secretion in girls with isolated gonadotrophin deficiency. Plasma prolactin, basal levels and the response to an i.v. injection of TRH (100 microgram/m2) was determined in five girls with isolated gonadotrophin deficiency of hypothalamic origin before and after at least 3 months cyclic replacement therapy with conjugated oestrogens (1.25 mg/day). The basal plasma prolactin levels were similar during both tests, however, during oestrogen therapy the mean peak response to TRH almost doubled and the sum of all the values obtained (basal, +15, +30 and +60 min) was significantly higher. It is of note that even upon prolonged oestrogen deprivation the releasable prolactin response to TRH was adequate."}
{"id": "PMID:201408", "title": "E-rosette inhibiting substance in Hodgkin's disease spleen extracts.", "content": "Patients with Hodgkin's disease often manifest impairment of cell-mediated immune responses in both in vivo and in vitro tests, as well as a markedly decreased percentage of E rosette-forming (T) lymphocytes in the peripheral blood. This report describes the inhibition of E-rosette formation by normal peripheral blood lymphocytes after incubation with extracts prepared from the spleens of patients with Hodgkin's disease. Such extracts also depressed E-rosette formation by the peripheral blood lymphocytes of patients with Hodgkin's disease after those cells had been restored to normal function by prior incubation in foetal calf serum. Similarly prepared extracts from the spleens of normal donors had no immunodepressive effect. The E-rosette inhibitory substance in the Hodgkin's disease spleen extracts was found to be a complex containing beta-lipoprotein, C-reactive protein, and C1q.", "contents": "E-rosette inhibiting substance in Hodgkin's disease spleen extracts. Patients with Hodgkin's disease often manifest impairment of cell-mediated immune responses in both in vivo and in vitro tests, as well as a markedly decreased percentage of E rosette-forming (T) lymphocytes in the peripheral blood. This report describes the inhibition of E-rosette formation by normal peripheral blood lymphocytes after incubation with extracts prepared from the spleens of patients with Hodgkin's disease. Such extracts also depressed E-rosette formation by the peripheral blood lymphocytes of patients with Hodgkin's disease after those cells had been restored to normal function by prior incubation in foetal calf serum. Similarly prepared extracts from the spleens of normal donors had no immunodepressive effect. The E-rosette inhibitory substance in the Hodgkin's disease spleen extracts was found to be a complex containing beta-lipoprotein, C-reactive protein, and C1q."}
{"id": "PMID:201409", "title": "Transfer factor therapy in ataxia--telangiectasia.", "content": "The effects of weekly doses of transfer factor in four patients with ataxia--telangiectasia were investigated following a total course of 2 months therapy. Transfer factor administration showed no influence on the absolute lymphocyte counts, T-cell rosettes or antibody titres to EBV, but it caused conversion of skin-test reactivity and production of MIF to various antigens. There was a dissociation in blastic transformation response, the skin-test responses and MIF production. Serum interferon levels were low before, and 2, 6 and 24 hr after, therapy. Clinically no improvement in infections was observed following transfer factor therapy.", "contents": "Transfer factor therapy in ataxia--telangiectasia. The effects of weekly doses of transfer factor in four patients with ataxia--telangiectasia were investigated following a total course of 2 months therapy. Transfer factor administration showed no influence on the absolute lymphocyte counts, T-cell rosettes or antibody titres to EBV, but it caused conversion of skin-test reactivity and production of MIF to various antigens. There was a dissociation in blastic transformation response, the skin-test responses and MIF production. Serum interferon levels were low before, and 2, 6 and 24 hr after, therapy. Clinically no improvement in infections was observed following transfer factor therapy."}
{"id": "PMID:201414", "title": "Echo-encephalographic measurements (A-scan) of the lateral ventricles in children; its reliability.", "content": "A positioning of the probe on the skull has been developed to increase the diagnostic accuracy of hydrocephalus. Echo-encephalography in the trigonum region of the ventricles is usually possible in children up to 13 years of age. In this region sources of error as the medial wall of the temporal lobe or the lateral wall of the temporal horn are eliminated. In hydrocephalic ventricles the ultrasound measurements in this region corroborate very well with the measurements found in the pneumo-encephalograms. This in contrast to the measurements found with the probe placed in the more conventional region. As the largest diameter of the skull, corresponds with the trigonum region, a very practical topographic mark for a reliable standardized method has been found. With more confidence the ventricle indices of 93 normal children, in the age of 1 to 13 years, were measured.", "contents": "Echo-encephalographic measurements (A-scan) of the lateral ventricles in children; its reliability. A positioning of the probe on the skull has been developed to increase the diagnostic accuracy of hydrocephalus. Echo-encephalography in the trigonum region of the ventricles is usually possible in children up to 13 years of age. In this region sources of error as the medial wall of the temporal lobe or the lateral wall of the temporal horn are eliminated. In hydrocephalic ventricles the ultrasound measurements in this region corroborate very well with the measurements found in the pneumo-encephalograms. This in contrast to the measurements found with the probe placed in the more conventional region. As the largest diameter of the skull, corresponds with the trigonum region, a very practical topographic mark for a reliable standardized method has been found. With more confidence the ventricle indices of 93 normal children, in the age of 1 to 13 years, were measured."}
{"id": "PMID:201415", "title": "Computed tomography of supratentorial meningioma.", "content": "The appearance on C.T. of 28 meningiomas is described. On the plain scan they presented as a rounded, well defined lesion with a high density in 18 cases and a density equal to or lower than brain tissue in 10 cases. The density could be related to certain histologic features as the amount of connective tissue and extracellular water and the presence of psammoma bodies or lipid storage cells. After administration of contrast a homogeneous, markedly increased, sharply marginated density was seen in most meningiomas. Contrast enhancement appeared to be dependent on the vascularity of the tumour. +/- 50% of the cases demonstrated edema grade II or III. On first interpretation 93% of the meningiomas were recognized as a lesion and a tumour (2 false negative) and 79% as a meningioma (2 false negative and 4 incorrect). Only one false positive C.T. scan was encountered. As a screening method R.N. scanning has about the same accuracy as C.T.; in establishing a definite diagnosis angiography equals C.T.; but C.T. is superior as it combines the diagnostic qualities of both methods.", "contents": "Computed tomography of supratentorial meningioma. The appearance on C.T. of 28 meningiomas is described. On the plain scan they presented as a rounded, well defined lesion with a high density in 18 cases and a density equal to or lower than brain tissue in 10 cases. The density could be related to certain histologic features as the amount of connective tissue and extracellular water and the presence of psammoma bodies or lipid storage cells. After administration of contrast a homogeneous, markedly increased, sharply marginated density was seen in most meningiomas. Contrast enhancement appeared to be dependent on the vascularity of the tumour. +/- 50% of the cases demonstrated edema grade II or III. On first interpretation 93% of the meningiomas were recognized as a lesion and a tumour (2 false negative) and 79% as a meningioma (2 false negative and 4 incorrect). Only one false positive C.T. scan was encountered. As a screening method R.N. scanning has about the same accuracy as C.T.; in establishing a definite diagnosis angiography equals C.T.; but C.T. is superior as it combines the diagnostic qualities of both methods."}
{"id": "PMID:201416", "title": "Doppler haematotachography: problems in interpretation and new applications.", "content": "The Doppler-echographic examination (HTG) seems to be developing into a screening method for the detection of abnormalities of the large cerebropetal vessels. An appraisal is made of the possibilities and limitations of the HTG based on the literature, a group of 250 patients and several relevant case histories. In general an abnormal HTG curve seems to warrant further diagnostic investigations (angiography). A normal HTG curve not be considered sufficient reason to omit an angiographic examination. A number of new applications of the HTG examination are mentioned.", "contents": "Doppler haematotachography: problems in interpretation and new applications. The Doppler-echographic examination (HTG) seems to be developing into a screening method for the detection of abnormalities of the large cerebropetal vessels. An appraisal is made of the possibilities and limitations of the HTG based on the literature, a group of 250 patients and several relevant case histories. In general an abnormal HTG curve seems to warrant further diagnostic investigations (angiography). A normal HTG curve not be considered sufficient reason to omit an angiographic examination. A number of new applications of the HTG examination are mentioned."}
{"id": "PMID:201417", "title": "Siderophages in differentiation of blood in cerebrospinal fluid.", "content": "This paper evaluates demonstration of siderophages as a method of differentiating blood in CSF. Of 1147 CSF samples, 125 were selected which had been obtained by lumbar puncture from patients with proven intracranial haemorrhage (spontaneous or traumatic) after an exactly known interval since the onset of clinical phenomena (haemorrhage or accident). No siderophages were found within 24 hours; in a few cases they were found on the second or the third day, and after that time they were found in the majority of cases. This is a pathognomonic finding. Collection of CSF in successive portions, qualification of the tap by the clinician as 'traumatic' or 'atraumatic', and demonstration of crenated red cells, were found to be unreliable methods. A modified apparatus for sedimentation is described.", "contents": "Siderophages in differentiation of blood in cerebrospinal fluid. This paper evaluates demonstration of siderophages as a method of differentiating blood in CSF. Of 1147 CSF samples, 125 were selected which had been obtained by lumbar puncture from patients with proven intracranial haemorrhage (spontaneous or traumatic) after an exactly known interval since the onset of clinical phenomena (haemorrhage or accident). No siderophages were found within 24 hours; in a few cases they were found on the second or the third day, and after that time they were found in the majority of cases. This is a pathognomonic finding. Collection of CSF in successive portions, qualification of the tap by the clinician as 'traumatic' or 'atraumatic', and demonstration of crenated red cells, were found to be unreliable methods. A modified apparatus for sedimentation is described."}
{"id": "PMID:201421", "title": "Regulation of gluconeogenesis and ketogenesis during rest and exercise in diabetic subjects and normal men.", "content": "The splanchnic-hepatic metabolism of glucose, lactate, pyruvate, alanine, glycerol, non-esterified fatty acids (NEFA), ketone bodies and oxygen were investigated in five normal men and six juvenile diabetic subjects at rest and during exercise after an overnight fast. A linear relationship was found between load (arterial concentration multiplied by hepatic blood flow) and splanchnic-hepatic uptake of lactate, pyruvate, glycerol and NEFA. The uptake of alanine was highly sensitive to load, but was also regulated by the concentration of hepatic venous glucagon. The uptake of pyruvate was high in exercising diabetic subjects, who had a high lactate/pyruvate concentration ratio in hepatic venous blood. The rate of uptake of the total measured gluconeogenic precursors was significantly higher in the diabetic group at a given load. The rate of ketogenesis was linearly related to the NEFA load in both groups; however, the rate of ketogenesis was twofold at a given load in the diabetic group. The highest rates of ketogenesis were found coincident with the highest concentrations of glucagon in hepatic venous blood. The observed antiketogenic effect of exercise was due to a decreased load of NEFA, mainly caused by a decrease in the hepatic blood flow.", "contents": "Regulation of gluconeogenesis and ketogenesis during rest and exercise in diabetic subjects and normal men. The splanchnic-hepatic metabolism of glucose, lactate, pyruvate, alanine, glycerol, non-esterified fatty acids (NEFA), ketone bodies and oxygen were investigated in five normal men and six juvenile diabetic subjects at rest and during exercise after an overnight fast. A linear relationship was found between load (arterial concentration multiplied by hepatic blood flow) and splanchnic-hepatic uptake of lactate, pyruvate, glycerol and NEFA. The uptake of alanine was highly sensitive to load, but was also regulated by the concentration of hepatic venous glucagon. The uptake of pyruvate was high in exercising diabetic subjects, who had a high lactate/pyruvate concentration ratio in hepatic venous blood. The rate of uptake of the total measured gluconeogenic precursors was significantly higher in the diabetic group at a given load. The rate of ketogenesis was linearly related to the NEFA load in both groups; however, the rate of ketogenesis was twofold at a given load in the diabetic group. The highest rates of ketogenesis were found coincident with the highest concentrations of glucagon in hepatic venous blood. The observed antiketogenic effect of exercise was due to a decreased load of NEFA, mainly caused by a decrease in the hepatic blood flow."}
{"id": "PMID:201423", "title": "Role of cyclic AMP in the natriuresis of extracellular fluid volume expansion in the dog.", "content": "1. The effect of extracellular volume expansion (ECVE) on renal production of cyclic AMP was evaluated in 19 thyroparathyroidectomized dogs. ECVE was produced by the infusion of Ringer bicarbonate solution at a rate of 2 ml min-1 kg-1 body weight; cyclic AMP was measured in plasma obtained from the aorta and renal vein and in the urine. 2. During the natriuresis of ECVE urinary excretion of cyclic AMP, the clearance of cyclic AMP, net nephrogenous cyclic AMP added both to urine and to the renal vein and hence total nephrogenous cyclic AMP increased significantly. 3. This rise in net production of cyclic AMP and a significant natriuresis by the kidney persisted for 60--90 min after discontinuation of active ECVE and return of renal plasma flow to normal. 4. The results support the notion that an increase in the production of cyclic AMP by the kidney may play a role in the natriuresis of ECVE.", "contents": "Role of cyclic AMP in the natriuresis of extracellular fluid volume expansion in the dog. 1. The effect of extracellular volume expansion (ECVE) on renal production of cyclic AMP was evaluated in 19 thyroparathyroidectomized dogs. ECVE was produced by the infusion of Ringer bicarbonate solution at a rate of 2 ml min-1 kg-1 body weight; cyclic AMP was measured in plasma obtained from the aorta and renal vein and in the urine. 2. During the natriuresis of ECVE urinary excretion of cyclic AMP, the clearance of cyclic AMP, net nephrogenous cyclic AMP added both to urine and to the renal vein and hence total nephrogenous cyclic AMP increased significantly. 3. This rise in net production of cyclic AMP and a significant natriuresis by the kidney persisted for 60--90 min after discontinuation of active ECVE and return of renal plasma flow to normal. 4. The results support the notion that an increase in the production of cyclic AMP by the kidney may play a role in the natriuresis of ECVE."}
{"id": "PMID:201425", "title": "Interaction of papaverine and isoproterenol in the vascular system of the dog and intestinal smooth muscle of the rabbit.", "content": "It was found that the effect of isoproterenol on the vasculature of the anesthetized dog can be potentiated by previous administration of papaverine. This effect is apparent in spite of concomitant potentiation of inotropic and/or chronotropic effects, which tend to obscure the vasomotor effect. Evidence is presented supporting the hypothesis that papaverine interacts with receptors of the vascular tree, which are usually classified as beta receptors and are responsive to isoproterenol. Evidence is presented showing almost complete inhibition of the chronotropic effects of papaverine by propranolol, and a synergism of papaverine with the chronotropic effects of isoproterenol. Evidence was obtained using the intestinal smooth muscle of the rabbit in support of the hypothesis linking mediation of the beta adrenergic system to papaverine effects.", "contents": "Interaction of papaverine and isoproterenol in the vascular system of the dog and intestinal smooth muscle of the rabbit. It was found that the effect of isoproterenol on the vasculature of the anesthetized dog can be potentiated by previous administration of papaverine. This effect is apparent in spite of concomitant potentiation of inotropic and/or chronotropic effects, which tend to obscure the vasomotor effect. Evidence is presented supporting the hypothesis that papaverine interacts with receptors of the vascular tree, which are usually classified as beta receptors and are responsive to isoproterenol. Evidence is presented showing almost complete inhibition of the chronotropic effects of papaverine by propranolol, and a synergism of papaverine with the chronotropic effects of isoproterenol. Evidence was obtained using the intestinal smooth muscle of the rabbit in support of the hypothesis linking mediation of the beta adrenergic system to papaverine effects."}
{"id": "PMID:201426", "title": "Peyote, a potential ethnopharmacologic agent for alcoholism and other drug dependencies: possible biochemical rationale.", "content": "The authors examine folk psychiatry among Native American Church members from an enthnopharmacologic viewpoint. Alcohol and opiate abuse among Indian and non-Indian are presented in case histories proving to be asymptomatic under Indian guidance and through participation in the peyote ritual. The biochemical alkaloids common in the peyote cactus, rather than just the psychoactive substances (mescaline), are purported to be pharmacologically similar to the neuroamine-derived alkaloids found in the brain during alcohol intoxification. Evidence is reviewed that points out possible common features of alcohol and opiate dependence leading to the speculation for a common mode of treatment may reside in plants rich in isoquinoline alkaloids.", "contents": "Peyote, a potential ethnopharmacologic agent for alcoholism and other drug dependencies: possible biochemical rationale. The authors examine folk psychiatry among Native American Church members from an enthnopharmacologic viewpoint. Alcohol and opiate abuse among Indian and non-Indian are presented in case histories proving to be asymptomatic under Indian guidance and through participation in the peyote ritual. The biochemical alkaloids common in the peyote cactus, rather than just the psychoactive substances (mescaline), are purported to be pharmacologically similar to the neuroamine-derived alkaloids found in the brain during alcohol intoxification. Evidence is reviewed that points out possible common features of alcohol and opiate dependence leading to the speculation for a common mode of treatment may reside in plants rich in isoquinoline alkaloids."}
{"id": "PMID:201427", "title": "Allergic contact dermatitis to a photopolymerizable resin used in printing.", "content": "Organic photopolymerizable resins increasingly used in printing make it possible to produce flexible, lighter plates. A certain number of skin lesions and general symptoms appeared upon manipulation of plates made by the Letterflex process. In the workshop where this study was carried out, 12 out of 15 people suffered various degrees of skin lesions. The epicutaneous tests and biopsies performed indicate an allergic type reaction to one of the resin's constituents, polythiol. Experiments with animals confirm the strong allergenicity of this compound.", "contents": "Allergic contact dermatitis to a photopolymerizable resin used in printing. Organic photopolymerizable resins increasingly used in printing make it possible to produce flexible, lighter plates. A certain number of skin lesions and general symptoms appeared upon manipulation of plates made by the Letterflex process. In the workshop where this study was carried out, 12 out of 15 people suffered various degrees of skin lesions. The epicutaneous tests and biopsies performed indicate an allergic type reaction to one of the resin's constituents, polythiol. Experiments with animals confirm the strong allergenicity of this compound."}
{"id": "PMID:201430", "title": "Adrenocortical function after stimulation with synthetic ACTH.", "content": "In order to assess the effect of ACTH on the adrenal cortex when used as a therapeutic or diagnostic agent, adrenocortical function was tested before and 2 hours after 0.5 mg tetracosactrin given intramuscularly in 31 healthy children, divided into 4 groups according to age and sex. Mean plasma cortisol levels were shown to be 184% higher than baseline values after administration of the drug, and there were no significant differences related to age or sex. It is suggested that this simple test can be of practical value in the diagnosis of adrenocortical function in young people.", "contents": "Adrenocortical function after stimulation with synthetic ACTH. In order to assess the effect of ACTH on the adrenal cortex when used as a therapeutic or diagnostic agent, adrenocortical function was tested before and 2 hours after 0.5 mg tetracosactrin given intramuscularly in 31 healthy children, divided into 4 groups according to age and sex. Mean plasma cortisol levels were shown to be 184% higher than baseline values after administration of the drug, and there were no significant differences related to age or sex. It is suggested that this simple test can be of practical value in the diagnosis of adrenocortical function in young people."}
{"id": "PMID:201432", "title": "Ultrastructural features of human galactosaemic fibroblasts: effects of different nutritional environments.", "content": "The ultrastructural characteristics of galactosaemic human fibroblasts exposed to media with various sugars were compared. Considerations of known biochemical pathways suggested that cells without the galactokinase enzyme and exposed to galactose would be functionally equivalent to cells in a medium without any sugar source. We found the ultrastructural characteristics of such cells to be consistent with that hypothesis. In addition, we unexpectedly found that homozygous galactosaemic fibroblasts, exposed to medium with glucose as the energy source, showed evidence of degeneration, such as autophagic vacuoles. Degenerative changes were not found in fibroblasts heterozygous for the galactokinase enzyme exposed to glucose. The implications and uses of these findings are discussed.", "contents": "Ultrastructural features of human galactosaemic fibroblasts: effects of different nutritional environments. The ultrastructural characteristics of galactosaemic human fibroblasts exposed to media with various sugars were compared. Considerations of known biochemical pathways suggested that cells without the galactokinase enzyme and exposed to galactose would be functionally equivalent to cells in a medium without any sugar source. We found the ultrastructural characteristics of such cells to be consistent with that hypothesis. In addition, we unexpectedly found that homozygous galactosaemic fibroblasts, exposed to medium with glucose as the energy source, showed evidence of degeneration, such as autophagic vacuoles. Degenerative changes were not found in fibroblasts heterozygous for the galactokinase enzyme exposed to glucose. The implications and uses of these findings are discussed."}
{"id": "PMID:201433", "title": "Effect of vitamin D3 on duodenal absorptive cell plasma membranes: freeze fracture replication study.", "content": "Vitamin D3 induced changes in the number of 5.8 nm sized randomly scattered particles on the EF faces of plasma membranes of chick duodenal absorptive cells. Their number increased as compared to those in rachitic animals. Also vitamin D3 seemed to alter the nature of the zonula occludens. These changes appear to be related to increased active absorption and passive diffusion of calcium respectively under vitamin D3 influence.", "contents": "Effect of vitamin D3 on duodenal absorptive cell plasma membranes: freeze fracture replication study. Vitamin D3 induced changes in the number of 5.8 nm sized randomly scattered particles on the EF faces of plasma membranes of chick duodenal absorptive cells. Their number increased as compared to those in rachitic animals. Also vitamin D3 seemed to alter the nature of the zonula occludens. These changes appear to be related to increased active absorption and passive diffusion of calcium respectively under vitamin D3 influence."}
{"id": "PMID:201440", "title": "[Biological availability of fluoride after combined administration with vitamin D3 in man (author's transl)].", "content": "Six adults ingested 1 mg fluoride, first as NaF in a watery solution and, secondly, in tablet form (D-Fluoretten 1000). Fluoride concentration was almost identical in the two series. After initial values within the normal range concentrations rapidly rose to a maximum (six times normal) reached on average after 30 minutes, followed by an, at first steep then more gradual, fall in concentration over eight hours. The area under the curve was similar in the two series. These results indicate that the biological availability of fluoride is not influenced by vitamin D3 in the adult and, presumably, in the small child as well.", "contents": "[Biological availability of fluoride after combined administration with vitamin D3 in man (author's transl)]. Six adults ingested 1 mg fluoride, first as NaF in a watery solution and, secondly, in tablet form (D-Fluoretten 1000). Fluoride concentration was almost identical in the two series. After initial values within the normal range concentrations rapidly rose to a maximum (six times normal) reached on average after 30 minutes, followed by an, at first steep then more gradual, fall in concentration over eight hours. The area under the curve was similar in the two series. These results indicate that the biological availability of fluoride is not influenced by vitamin D3 in the adult and, presumably, in the small child as well."}
{"id": "PMID:201441", "title": "Metoprolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris.", "content": "Metoprolol is a beta1-selective adrenoceptor blocking drug. In hypertension, its duration of effect is longer than expected from its half-life and it is suitable for twice daily administration. There is some evidence that once daily administration may be possible in treating hypertension. It is similar in efficacy to other beta-adrenoceptor blocking drugs in angina pectoris and essential hypertension, when given in equiactive beta-blocking dosages. Metoprolol is well tolerated and side-effects have not proved a problem. It has some pharmacodynamic and pharmacokinetic differences from other beta-adrenoceptor blocking drugs and may prove useful in cases where these differences are shown to be clinically important.", "contents": "Metoprolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris. Metoprolol is a beta1-selective adrenoceptor blocking drug. In hypertension, its duration of effect is longer than expected from its half-life and it is suitable for twice daily administration. There is some evidence that once daily administration may be possible in treating hypertension. It is similar in efficacy to other beta-adrenoceptor blocking drugs in angina pectoris and essential hypertension, when given in equiactive beta-blocking dosages. Metoprolol is well tolerated and side-effects have not proved a problem. It has some pharmacodynamic and pharmacokinetic differences from other beta-adrenoceptor blocking drugs and may prove useful in cases where these differences are shown to be clinically important."}
{"id": "PMID:201446", "title": "[Participation of cyclic-3',5'-adenosine monophosphate in the pathogenesis of myocardial hypertrophy in experimental hypertension].", "content": "The authors examined the concentration of cAMP in the myocardium of rats with experimental hypertension during various periods after modeling of the process. The changes in the values of cyclic nucleotide corresponded to the dynamics of the development of the arterial hypertension. There was na increase of the level of cAMP in the myocardium on the third day after modeling of hypertension, accompanying the initial elevation of the arterial pressure. The maximal values of cAMP were established on the 30th day, which corresponded to the maximal development of hypertension. Cyclic 3,5-adenomonophosphate began to diminish parallel to the lowering of the arterial pressure during the chronic phase 90th day. The obtained results give a possibility to discuss the participation of cAMP in the pathogenesis of myocardial hypertension, occurring in experimental hypertension.", "contents": "[Participation of cyclic-3',5'-adenosine monophosphate in the pathogenesis of myocardial hypertrophy in experimental hypertension]. The authors examined the concentration of cAMP in the myocardium of rats with experimental hypertension during various periods after modeling of the process. The changes in the values of cyclic nucleotide corresponded to the dynamics of the development of the arterial hypertension. There was na increase of the level of cAMP in the myocardium on the third day after modeling of hypertension, accompanying the initial elevation of the arterial pressure. The maximal values of cAMP were established on the 30th day, which corresponded to the maximal development of hypertension. Cyclic 3,5-adenomonophosphate began to diminish parallel to the lowering of the arterial pressure during the chronic phase 90th day. The obtained results give a possibility to discuss the participation of cAMP in the pathogenesis of myocardial hypertension, occurring in experimental hypertension."}
{"id": "PMID:201447", "title": "[Rest-activity-cycle and stereotyped hand waving of a mentally defective child (author's transl)].", "content": "Stereotyped acts of a mentally defective girl. 6;6 years old, were observed from 6 a.m. till 8 p.m. during 16 days. Alternating phases of more or less frequent stereotyped hand waving showed a prominent periodicity of about 90 minutes. Sleep stages were also determined polygraphically during 10 nights. As statistically proved the mean peak-to-peak interval of the stereotyped activity at days corresponded to the mean REM- to REM period of nights. This suggests, that the stereotyped behavior of this child was driven by the basic rest activity cycle already described by Kleitman. The mean periodicity of sleep stages was represented by modeled rhythms adapted to the scored sleep stages. If the model rhythms of all 10 nights were extended backward to the preceding days, they paralleled the stereotyped activity. Half periods found in phase with REM stages corresponded to the maxima of the stereotyped activity. It will be discussed that the basic rest activity cycle triggers sensory as well as motor mechanisms characterizing both the phases of enhanced stereotyped activity and REM stages.", "contents": "[Rest-activity-cycle and stereotyped hand waving of a mentally defective child (author's transl)]. Stereotyped acts of a mentally defective girl. 6;6 years old, were observed from 6 a.m. till 8 p.m. during 16 days. Alternating phases of more or less frequent stereotyped hand waving showed a prominent periodicity of about 90 minutes. Sleep stages were also determined polygraphically during 10 nights. As statistically proved the mean peak-to-peak interval of the stereotyped activity at days corresponded to the mean REM- to REM period of nights. This suggests, that the stereotyped behavior of this child was driven by the basic rest activity cycle already described by Kleitman. The mean periodicity of sleep stages was represented by modeled rhythms adapted to the scored sleep stages. If the model rhythms of all 10 nights were extended backward to the preceding days, they paralleled the stereotyped activity. Half periods found in phase with REM stages corresponded to the maxima of the stereotyped activity. It will be discussed that the basic rest activity cycle triggers sensory as well as motor mechanisms characterizing both the phases of enhanced stereotyped activity and REM stages."}
{"id": "PMID:201449", "title": "Inhibition of cortiocosteroidogenesis by delta-9-tetrahydrocannabinol.", "content": "ACTH, cholera toxin, cyclic AMP but not pregnenolone-induced steroidogenesis in Y-1 functional mouse adrenal tumor cells was significantly inhibited by delta-9-tetrahydrocannabinol, cannabidiol, and cannabinol. The inhibition of steroidogenesis could not be correlated with a general depression in cell function or viability. The data suggest that cannabinoids inhibit corticosteroidogenesis at a site between the synthesis of cAMP and of pregnenolone.", "contents": "Inhibition of cortiocosteroidogenesis by delta-9-tetrahydrocannabinol. ACTH, cholera toxin, cyclic AMP but not pregnenolone-induced steroidogenesis in Y-1 functional mouse adrenal tumor cells was significantly inhibited by delta-9-tetrahydrocannabinol, cannabidiol, and cannabinol. The inhibition of steroidogenesis could not be correlated with a general depression in cell function or viability. The data suggest that cannabinoids inhibit corticosteroidogenesis at a site between the synthesis of cAMP and of pregnenolone."}
{"id": "PMID:201450", "title": "Identification of beta-adrenergic binding sites in rabbit myometrium.", "content": "Rabbit uterine muscle may contract or relax with adrenergic stimulation depending on the hormonal milieu. This difference in contractile activity has been shown to be due to alteration of adrenergic response between alpha-adrenergic (contraction) and beta-adrenergic (relaxation). When rabbits are treated with estrogen followed by progesterone, norepinephrine produces myometrial relaxation. This effect is blocked by propranolol, indicating that it is mediated by beta receptor activation. A subcellular preparation of this myometrium has adenylate cyclase activity that can be stimulated by isoproterenol + guanyl-5'-yl-imidodi-phosphate (Gpp(NH)p). The radioligand [125I]iodohydroxybenzylpindolol binds to the same preparation. The binding is rapid, 80% maximal in 10 min, and readily reversible (t1/2 = 5 min). The binding is high affinity (Kd = 0.12 nM), low capacity (15 fmol/mg protein), and is to a single class of binding sites. Binding is competed for stereoselectively by beta adrenergic agonists and antagonists. The competition of beta adrenergic agonists for binding, isoproterenol = ritodrine greater than epinephrine greater than norepinephrine, is consistent with interactions at a beta2-adrenergic receptor.", "contents": "Identification of beta-adrenergic binding sites in rabbit myometrium. Rabbit uterine muscle may contract or relax with adrenergic stimulation depending on the hormonal milieu. This difference in contractile activity has been shown to be due to alteration of adrenergic response between alpha-adrenergic (contraction) and beta-adrenergic (relaxation). When rabbits are treated with estrogen followed by progesterone, norepinephrine produces myometrial relaxation. This effect is blocked by propranolol, indicating that it is mediated by beta receptor activation. A subcellular preparation of this myometrium has adenylate cyclase activity that can be stimulated by isoproterenol + guanyl-5'-yl-imidodi-phosphate (Gpp(NH)p). The radioligand [125I]iodohydroxybenzylpindolol binds to the same preparation. The binding is rapid, 80% maximal in 10 min, and readily reversible (t1/2 = 5 min). The binding is high affinity (Kd = 0.12 nM), low capacity (15 fmol/mg protein), and is to a single class of binding sites. Binding is competed for stereoselectively by beta adrenergic agonists and antagonists. The competition of beta adrenergic agonists for binding, isoproterenol = ritodrine greater than epinephrine greater than norepinephrine, is consistent with interactions at a beta2-adrenergic receptor."}
{"id": "PMID:201452", "title": "Potent inhibitory activity of [D-Leu6, Des-Gly-NH2(10)]LHRH ethylamide on LH/hCG and PRL testicular receptor levels in the rat.", "content": "Injection of male rats with 40-200 ng of [D-Leu6, des-Gly-NH2(10)]LHRH ethylamide for 7 days caused a maximal 80% reduction of testicular LH/hCG receptor level with one injection per day being as efficient as 3 daily injections. A similar inhibitory effect was observed on testicular PRL receptors. Testis and seminal vesicle weight as well as plasma testosterone levels were also significantly reduced by this treatment. These data indicate that a LHRH agonist, when given at a relatively low dose, is capable of reducing testicular LH/hCG and PRL receptor levels as well as testicular function, the effect being probably mediated by increased endogenous gonadotropin secretion.", "contents": "Potent inhibitory activity of [D-Leu6, Des-Gly-NH2(10)]LHRH ethylamide on LH/hCG and PRL testicular receptor levels in the rat. Injection of male rats with 40-200 ng of [D-Leu6, des-Gly-NH2(10)]LHRH ethylamide for 7 days caused a maximal 80% reduction of testicular LH/hCG receptor level with one injection per day being as efficient as 3 daily injections. A similar inhibitory effect was observed on testicular PRL receptors. Testis and seminal vesicle weight as well as plasma testosterone levels were also significantly reduced by this treatment. These data indicate that a LHRH agonist, when given at a relatively low dose, is capable of reducing testicular LH/hCG and PRL receptor levels as well as testicular function, the effect being probably mediated by increased endogenous gonadotropin secretion."}
{"id": "PMID:201453", "title": "Rat adrenal corticosteroidogenesis; effect of ACTH, cycloheximide and sterol carrier protein.", "content": "Corticosterone formation was determined in the reconstructed rat adrenal system which consisted of the mitochondria and post-mitochondrial supernatant fraction (PM-fraction) supported by l-malate, and effect of ACTH and cycloheximide in vivo and cycloheximide, Ca++ and sterol carrier protein (SCP) in vitro were examined. Mitochondria isolated from adrenals of rats which received ACTH 15 min before sacrifice showed an elevated corticosterone formation. Cycloheximide administration 15 min prior to ACTH injection completely blocked the effect of ACTH but in vitro addition of this drug to the incubation mixture did not modify the rate of corticosterone production even at higher concentrations. Since the PM-fraction isolated from adrenals of rats received ACTH or cycloheximide or both did not change the mitochondrial capacity for corticosterone formation, factor(s) which influenced by ACTH administration seemed to be localized in mitochondria. The SCP-bound cholesterol was utilized for corticosterone formation more efficiently than the free cholesterol when added to the incubation mixture, and this might be due to, at least in part, higher rate of binding to the mitochondrial inner membrane of the SCP-bound cholesterol.", "contents": "Rat adrenal corticosteroidogenesis; effect of ACTH, cycloheximide and sterol carrier protein. Corticosterone formation was determined in the reconstructed rat adrenal system which consisted of the mitochondria and post-mitochondrial supernatant fraction (PM-fraction) supported by l-malate, and effect of ACTH and cycloheximide in vivo and cycloheximide, Ca++ and sterol carrier protein (SCP) in vitro were examined. Mitochondria isolated from adrenals of rats which received ACTH 15 min before sacrifice showed an elevated corticosterone formation. Cycloheximide administration 15 min prior to ACTH injection completely blocked the effect of ACTH but in vitro addition of this drug to the incubation mixture did not modify the rate of corticosterone production even at higher concentrations. Since the PM-fraction isolated from adrenals of rats received ACTH or cycloheximide or both did not change the mitochondrial capacity for corticosterone formation, factor(s) which influenced by ACTH administration seemed to be localized in mitochondria. The SCP-bound cholesterol was utilized for corticosterone formation more efficiently than the free cholesterol when added to the incubation mixture, and this might be due to, at least in part, higher rate of binding to the mitochondrial inner membrane of the SCP-bound cholesterol."}
{"id": "PMID:201455", "title": "The metabolism of 17beta-estradiol-3-glucosiduronate and estrone-3-glucosiduronate in the rabbit.", "content": "[6, 7-3H]-17beta-Estradiol-3-glucosiduronate, [6, 7-3H]-estrone-3-glucosiduronate or [6, 7-3H]-estrone was administered intravenously into the rabbit, and analysis and identification of the urinary metabolites were carried out. In either case, the major urinary metabolite was found to be a diconjugate. The sequential enzymic hydrolysis indicated that this diconjugate was glucosiduronate-N-acetyglucosaminide of 17alpha-estradiol. From these results, the conversion of the estrogen glucosiduronate into a diconjugate was thought a rather universal phenomenon in the rabbit.", "contents": "The metabolism of 17beta-estradiol-3-glucosiduronate and estrone-3-glucosiduronate in the rabbit. [6, 7-3H]-17beta-Estradiol-3-glucosiduronate, [6, 7-3H]-estrone-3-glucosiduronate or [6, 7-3H]-estrone was administered intravenously into the rabbit, and analysis and identification of the urinary metabolites were carried out. In either case, the major urinary metabolite was found to be a diconjugate. The sequential enzymic hydrolysis indicated that this diconjugate was glucosiduronate-N-acetyglucosaminide of 17alpha-estradiol. From these results, the conversion of the estrogen glucosiduronate into a diconjugate was thought a rather universal phenomenon in the rabbit."}
{"id": "PMID:201456", "title": "Theophylline stimulation of binding of radioiodinated rat prolactin to murine mammary gland.", "content": "Characteristics of prolactin receptors of murine mammary glands were studied. Mammary gland exhibited low but specific binding to 125I-rPRL (rat prolactin). Receptors were heat susceptible and partly protein in nature. Theophylline--both in vitro and in vivo treatment--enhanced the binding of 125I-rPRL to receptors. It remains to be established whether this action of theophylline is mediated through cyclic AMP \"Sparing\" effect or through its direct effect on cell membrane stabilization.", "contents": "Theophylline stimulation of binding of radioiodinated rat prolactin to murine mammary gland. Characteristics of prolactin receptors of murine mammary glands were studied. Mammary gland exhibited low but specific binding to 125I-rPRL (rat prolactin). Receptors were heat susceptible and partly protein in nature. Theophylline--both in vitro and in vivo treatment--enhanced the binding of 125I-rPRL to receptors. It remains to be established whether this action of theophylline is mediated through cyclic AMP \"Sparing\" effect or through its direct effect on cell membrane stabilization."}
{"id": "PMID:201457", "title": "Binding of thyroxine and triiodothyronine in solubilized nuclear extract of human leukocytes.", "content": "An in vitro study was carried out of the interaction of thyroidal hormones with leukocytes and with a solubilized extract of the nuclear fraction of human leukocytes. The respective association constants characterising the binding of triiodothyronine (T3) and thyroxine (T4) to whole leukocytes are roughly equal (for T3, KA = 3.1 X 10(11) 1/mol and for T4, KA = 4 X 10(11) 1/mol) but a 0.4 KCl extract of the nuclear fraction exhibits a different affinity to T3 (KA = 2.16 X 10(11) 1/mol) in comparison with T4 (KA = 1.3 X 10(10) 1/mol). In the nuclear extract, both hormones are bound with the affinity higher for T3 than for T4. The soluble nuclear binding protein in human leukocytes had a molecular weight 46 000, was chromatographically homogenous in chromatography on Sepharose 2B and Sephadex G200, and exhibited a longlasting stability at -25 degrees C, without any marked change in the binding affinity to thyroidal hormones.", "contents": "Binding of thyroxine and triiodothyronine in solubilized nuclear extract of human leukocytes. An in vitro study was carried out of the interaction of thyroidal hormones with leukocytes and with a solubilized extract of the nuclear fraction of human leukocytes. The respective association constants characterising the binding of triiodothyronine (T3) and thyroxine (T4) to whole leukocytes are roughly equal (for T3, KA = 3.1 X 10(11) 1/mol and for T4, KA = 4 X 10(11) 1/mol) but a 0.4 KCl extract of the nuclear fraction exhibits a different affinity to T3 (KA = 2.16 X 10(11) 1/mol) in comparison with T4 (KA = 1.3 X 10(10) 1/mol). In the nuclear extract, both hormones are bound with the affinity higher for T3 than for T4. The soluble nuclear binding protein in human leukocytes had a molecular weight 46 000, was chromatographically homogenous in chromatography on Sepharose 2B and Sephadex G200, and exhibited a longlasting stability at -25 degrees C, without any marked change in the binding affinity to thyroidal hormones."}
{"id": "PMID:201458", "title": "Effect of combined dopaminergic and GABA-ergic stimulation on ouabain-induced epileptiform activity.", "content": "In this study we tested a hypothesis that dopamine and GABA receptor-stimulating agents given together might mutually potentiate their anticonvulsant activities. To test this hypothesis, experiments were performed on free-moving rabbits with epileptiform activity evoked by cortical application of ouabain. After combined treatment with apomorphine and GHBA 3 out of 6 animals displayed no EEG epileptiform activity, and in the remaining 3 rabbits this activity was greatly reduced. A combined pretreatment with apomorphine and GHBA abolished epileptiform EEG activity during the first hour and shortened it during the second hour, but not significantly. Apomorphine given together with amino-oxyacetic acid before ouabain completely abolished the epileptiform activity in 4 out of 6 animals. In the remaining 2 rabbits the latency of ouabain affect was prolonged, the epileptiform activity during the first hour was abolished, and it was markedly decreased during the next 2 hr (significantly from controls or groups receiving apomorphine or amino-oxyacetic acid). Phenytoin was less potent than apomorphine with GHBA or apomorphine given together with AOAA. The animals' behavior was observed.", "contents": "Effect of combined dopaminergic and GABA-ergic stimulation on ouabain-induced epileptiform activity. In this study we tested a hypothesis that dopamine and GABA receptor-stimulating agents given together might mutually potentiate their anticonvulsant activities. To test this hypothesis, experiments were performed on free-moving rabbits with epileptiform activity evoked by cortical application of ouabain. After combined treatment with apomorphine and GHBA 3 out of 6 animals displayed no EEG epileptiform activity, and in the remaining 3 rabbits this activity was greatly reduced. A combined pretreatment with apomorphine and GHBA abolished epileptiform EEG activity during the first hour and shortened it during the second hour, but not significantly. Apomorphine given together with amino-oxyacetic acid before ouabain completely abolished the epileptiform activity in 4 out of 6 animals. In the remaining 2 rabbits the latency of ouabain affect was prolonged, the epileptiform activity during the first hour was abolished, and it was markedly decreased during the next 2 hr (significantly from controls or groups receiving apomorphine or amino-oxyacetic acid). Phenytoin was less potent than apomorphine with GHBA or apomorphine given together with AOAA. The animals' behavior was observed."}
{"id": "PMID:201461", "title": "Enzymes of ammonia detoxication after portacaval shunt in the rat. I. Carbamylphosphate synthetase and aspartate transcarbamylase.", "content": "At high systemic blood concentrations ammonia may be partially deviated into the pathway of pyrimidine synthesis, as has been observed in different genetic defects of the urea cycle. The portacaval shunt (PCS) rat presents an animal model to study ammonia detoxication without an underlying enzyme defect in the urea cycle. Since ammonia may induce a deviation into the pyrimidine pathway by influencing enzymatic reactions involved in this pathway, the activity of carbamylphosphate synthetase and aspartate transcarbamylase in liver as well as the excretion of orotic acid in the urine were measured in rats 10, 20 and 30 days after PCS. The results suggest that in this experimental model ammonia may be channeled into the pyrimidine pathway leading to a stimulation of the first enzymatic step and to an increased  excretion of orotic acid.", "contents": "Enzymes of ammonia detoxication after portacaval shunt in the rat. I. Carbamylphosphate synthetase and aspartate transcarbamylase. At high systemic blood concentrations ammonia may be partially deviated into the pathway of pyrimidine synthesis, as has been observed in different genetic defects of the urea cycle. The portacaval shunt (PCS) rat presents an animal model to study ammonia detoxication without an underlying enzyme defect in the urea cycle. Since ammonia may induce a deviation into the pyrimidine pathway by influencing enzymatic reactions involved in this pathway, the activity of carbamylphosphate synthetase and aspartate transcarbamylase in liver as well as the excretion of orotic acid in the urine were measured in rats 10, 20 and 30 days after PCS. The results suggest that in this experimental model ammonia may be channeled into the pyrimidine pathway leading to a stimulation of the first enzymatic step and to an increased  excretion of orotic acid."}
{"id": "PMID:201463", "title": "Studies on the mechanism of action of histone kinase dependent on adenosine 3':5'-monophosphate. Evidence for involvement of histidine and lysine residues in the phosphotransferase reaction.", "content": "The reaction of the phosphate residue transfer catalysed by histone kinase dependent on adenosine 3':5'-monophosphate (cyclic AMP) was studied. The phosphotransferase reaction was shown to obey the mechanism of ping-pong bi-bi type. After incubation of the catalytic subunit of histone kinase with [gamma-32P]ATP the incorporation of one mole of [32P]phosphage per mole of protein was observed. The tryptic [32P]phosphohistidine-containing peptide was isolated and its N-terminus and amino acid composition were determined. The 2',3'-dialdehyde derivative of ATP (oATP) was used as the affinity label for the catalytic subunit of cyclic-AMP-dependent histone kinase. The inhibitor formed an alidmine bond with epsilon-amino group of the lysine residue of the active site and was irreversibly bound to the enzyme after reduction by sodium borohydride with concurrent irreversible inactivation of the enzyme. After inactivation, about one mole of 14C-labelled inhibitor was incorporated per mole of the enzyme. ATP effectively protected the catalytic subunit of histone kinase against inactivation by oATP. Tryptic digestion of the enzyme-inhibitor complex led to the isolation of the 14C-labelled peptide of the active site of histone kinase. Basing on these results, the role of histidine and lysine residues in the active site of the catalytic subunit of histone kinase was suggested.", "contents": "Studies on the mechanism of action of histone kinase dependent on adenosine 3':5'-monophosphate. Evidence for involvement of histidine and lysine residues in the phosphotransferase reaction. The reaction of the phosphate residue transfer catalysed by histone kinase dependent on adenosine 3':5'-monophosphate (cyclic AMP) was studied. The phosphotransferase reaction was shown to obey the mechanism of ping-pong bi-bi type. After incubation of the catalytic subunit of histone kinase with [gamma-32P]ATP the incorporation of one mole of [32P]phosphage per mole of protein was observed. The tryptic [32P]phosphohistidine-containing peptide was isolated and its N-terminus and amino acid composition were determined. The 2',3'-dialdehyde derivative of ATP (oATP) was used as the affinity label for the catalytic subunit of cyclic-AMP-dependent histone kinase. The inhibitor formed an alidmine bond with epsilon-amino group of the lysine residue of the active site and was irreversibly bound to the enzyme after reduction by sodium borohydride with concurrent irreversible inactivation of the enzyme. After inactivation, about one mole of 14C-labelled inhibitor was incorporated per mole of the enzyme. ATP effectively protected the catalytic subunit of histone kinase against inactivation by oATP. Tryptic digestion of the enzyme-inhibitor complex led to the isolation of the 14C-labelled peptide of the active site of histone kinase. Basing on these results, the role of histidine and lysine residues in the active site of the catalytic subunit of histone kinase was suggested."}
{"id": "PMID:201464", "title": "The Greig polysyndactyly-craniofacial dysmorphism syndrome.", "content": "A 15-month-old male child with the Greig polysyndactyly-craniofacial dysmorphism syndrome is presented and the relevant literature is reviewed.", "contents": "The Greig polysyndactyly-craniofacial dysmorphism syndrome. A 15-month-old male child with the Greig polysyndactyly-craniofacial dysmorphism syndrome is presented and the relevant literature is reviewed."}
{"id": "PMID:201465", "title": "Congenital scalp defect with distal limb reduction anomalies.", "content": "Congenital scalp defects and distal limb reduction anomalies can occur as separate entities or in combination with other anomalies. They also occur together in an apparently autosomal dominant syndrome, an example of which is described in the present paper. The literature on the subject is reviewed.", "contents": "Congenital scalp defect with distal limb reduction anomalies. Congenital scalp defects and distal limb reduction anomalies can occur as separate entities or in combination with other anomalies. They also occur together in an apparently autosomal dominant syndrome, an example of which is described in the present paper. The literature on the subject is reviewed."}
{"id": "PMID:201468", "title": "Increased growth of Rous sarcomas in chickens pretreated with formalinized syngeneic tumor cells.", "content": "The effect of inoculating formalinized syngeneic or allogeneic Rous sarcoma cells on the growth of Rous sarcoma virus (RSV)-induced tumors in two related inbred strains of chickens was studied. Chickens from both strains that received three weakly inoculations of syngeneic tumor cells had a significant increase in tumor growth and mortality after subsequent challenge with RSV. Development of RSV-induced tumors in chickens pretreated with formalinized allogeneic tumor cells (i.e. incompatible for major histocompatibility complex (MHC) antigens) was similar to what we observed in nonpretreated control chickens. The finding that the tumor-host relationship is altered only in chickens pretreated with formalinized syngeneic RSV-transformed cells, suggests that tumor-associated antigens of Rous sarcomas are modified MHC antigens analogous to \"altered self\" antigens thought to be present on certain virus-infected cells. If this hypothesis is correct, the results we obtained with formalin-killed syngeneic tumor cells can be explained on the basis of three possible mechanisms: immunological enhancement, immune tolerance or induction of antibody to anti-tumor idiotype. The merits of each mechanism in accounting for the results are discussed.", "contents": "Increased growth of Rous sarcomas in chickens pretreated with formalinized syngeneic tumor cells. The effect of inoculating formalinized syngeneic or allogeneic Rous sarcoma cells on the growth of Rous sarcoma virus (RSV)-induced tumors in two related inbred strains of chickens was studied. Chickens from both strains that received three weakly inoculations of syngeneic tumor cells had a significant increase in tumor growth and mortality after subsequent challenge with RSV. Development of RSV-induced tumors in chickens pretreated with formalinized allogeneic tumor cells (i.e. incompatible for major histocompatibility complex (MHC) antigens) was similar to what we observed in nonpretreated control chickens. The finding that the tumor-host relationship is altered only in chickens pretreated with formalinized syngeneic RSV-transformed cells, suggests that tumor-associated antigens of Rous sarcomas are modified MHC antigens analogous to \"altered self\" antigens thought to be present on certain virus-infected cells. If this hypothesis is correct, the results we obtained with formalin-killed syngeneic tumor cells can be explained on the basis of three possible mechanisms: immunological enhancement, immune tolerance or induction of antibody to anti-tumor idiotype. The merits of each mechanism in accounting for the results are discussed."}
{"id": "PMID:201469", "title": "Effects of pimozide on noradrenergic transmission in rabbit isolated ear arteries.", "content": "In the rabbit ear artery both dopamine and noradrenaline inhibit stimulation-induced (S-I) transmitter noradrenaline efflux. Pimozide, which is reported to be a specific dopamine receptor antagonist, was used to further study the effects of dopamine on transmitter efflux. In a concentration of 0.2 micrometer pimozide blocked the inhibition of S-I efflux produced by 0.5 micrometer dopamine but not that produced by 0.5 micrometer noradrenaline. In a concentration of 10 nM, pimozide enhances transmitter release and vasoconstrictor responses to sympathetic nerve stimulation; this may be due to blockade of feedback inhibition of transmitter release by endogenous dopamine. In a concentration of 1 micrometer, pimozide reduced transmitter release and vasoconstrictor responses to sympathetic nerve stimulation. Vasoconstrictor responses to noradrenaline and histamine are antagonized by pimozide in a noncompetitive manner.", "contents": "Effects of pimozide on noradrenergic transmission in rabbit isolated ear arteries. In the rabbit ear artery both dopamine and noradrenaline inhibit stimulation-induced (S-I) transmitter noradrenaline efflux. Pimozide, which is reported to be a specific dopamine receptor antagonist, was used to further study the effects of dopamine on transmitter efflux. In a concentration of 0.2 micrometer pimozide blocked the inhibition of S-I efflux produced by 0.5 micrometer dopamine but not that produced by 0.5 micrometer noradrenaline. In a concentration of 10 nM, pimozide enhances transmitter release and vasoconstrictor responses to sympathetic nerve stimulation; this may be due to blockade of feedback inhibition of transmitter release by endogenous dopamine. In a concentration of 1 micrometer, pimozide reduced transmitter release and vasoconstrictor responses to sympathetic nerve stimulation. Vasoconstrictor responses to noradrenaline and histamine are antagonized by pimozide in a noncompetitive manner."}
{"id": "PMID:201470", "title": "Effect of chlorpropamide and phenformin on rat liver: the effect on plasma membrane-bound enzymes and cyclic AMP content of hepatocytes in vitro.", "content": "Chlorpropamide and phenformin inhibited (Na+ - K+)-ATPase and stimulated a high affinity cyclic AMP-phosphodiesterase of isolated liver plasma membrane when tested in vitro. In addition, the two drugs decreased the intracellular cyclic AMP content of isolated hepatocytes without being effective on plasma membrane-bound adenylate cyclase. The results suggest that the plasma membrane plays an important role in the mechanism of action of the two hypoglycemic drugs, but do not exclude the presence of intracellular targets.", "contents": "Effect of chlorpropamide and phenformin on rat liver: the effect on plasma membrane-bound enzymes and cyclic AMP content of hepatocytes in vitro. Chlorpropamide and phenformin inhibited (Na+ - K+)-ATPase and stimulated a high affinity cyclic AMP-phosphodiesterase of isolated liver plasma membrane when tested in vitro. In addition, the two drugs decreased the intracellular cyclic AMP content of isolated hepatocytes without being effective on plasma membrane-bound adenylate cyclase. The results suggest that the plasma membrane plays an important role in the mechanism of action of the two hypoglycemic drugs, but do not exclude the presence of intracellular targets."}
{"id": "PMID:201471", "title": "Inhibition of angiotensin converting enzyme by SQ 14,225 in conscious rabbits.", "content": "The cardiovascular pharmacology of SQ 14,225 (D-3-mercapto-2-methylpropanoyl-L-proline), a new orally effective inhibitor of angiotensin-coverting enzyme (ACE) was investigated in conscious normotensive rabbits. Intravenous administration of SQ 14,225 (3.1-310.0 microgram/kg) resulted in a dose related inhibition of the pressor responses to 310 ng/kg, i.v. of angiotensin I (AI) without diminishing the pressor responses to 100 ng/kg, i.v. of angiotensin II (AII). In fact, the responsiveness of the rabbits to AII was significantly enhanced by higher doses of SQ 14,225. This enhancement of the pressor effects of AII was found to be related to the inhibition of ACE and the resulting decrease in the levels of endogenous AII. In addition, SQ 14,225 (1.0 mg/kg, i.v.) markedly potentiated the magnitude and duration of the vasodepressor responses elicited by bradykinin (1.0 microgram/kg. i.v.). At a dose of 1.0 mg/kg. i.v., SQ 14,225 had no effect on the vasodepressor effects of intravenously administered isoproterenol (0.4 microgram/kg), acetylcholine (1.0 microgram/kg) or prostaglandin E2 (3.0 microgram/kg, i.v.). The pressor responses to norepinephrine (3.0 microgram/kg, i.v.) were similarly unaffected by SQ 14,225 (1.0 mg/kg, i.v.). In normal rabbits SW 14,225 (1.0 mg/kg, i.v.) caused a small but significant decrease in arterial pressure; it had no such effect in anephric rabbits. The observation of this study indicate that SQ, 14,225 is a specific inhibitor of ACE in conscious rabbits.", "contents": "Inhibition of angiotensin converting enzyme by SQ 14,225 in conscious rabbits. The cardiovascular pharmacology of SQ 14,225 (D-3-mercapto-2-methylpropanoyl-L-proline), a new orally effective inhibitor of angiotensin-coverting enzyme (ACE) was investigated in conscious normotensive rabbits. Intravenous administration of SQ 14,225 (3.1-310.0 microgram/kg) resulted in a dose related inhibition of the pressor responses to 310 ng/kg, i.v. of angiotensin I (AI) without diminishing the pressor responses to 100 ng/kg, i.v. of angiotensin II (AII). In fact, the responsiveness of the rabbits to AII was significantly enhanced by higher doses of SQ 14,225. This enhancement of the pressor effects of AII was found to be related to the inhibition of ACE and the resulting decrease in the levels of endogenous AII. In addition, SQ 14,225 (1.0 mg/kg, i.v.) markedly potentiated the magnitude and duration of the vasodepressor responses elicited by bradykinin (1.0 microgram/kg. i.v.). At a dose of 1.0 mg/kg. i.v., SQ 14,225 had no effect on the vasodepressor effects of intravenously administered isoproterenol (0.4 microgram/kg), acetylcholine (1.0 microgram/kg) or prostaglandin E2 (3.0 microgram/kg, i.v.). The pressor responses to norepinephrine (3.0 microgram/kg, i.v.) were similarly unaffected by SQ 14,225 (1.0 mg/kg, i.v.). In normal rabbits SW 14,225 (1.0 mg/kg, i.v.) caused a small but significant decrease in arterial pressure; it had no such effect in anephric rabbits. The observation of this study indicate that SQ, 14,225 is a specific inhibitor of ACE in conscious rabbits."}
{"id": "PMID:201472", "title": "The effects of dibutyryl cyclic AMP, theophylline and papaverine on the release of 3H-catecholamines from rat brain striatal and cortical synaptosomes.", "content": "Papaverine enhances the spontaneous release of 3H-dopamine from rat brain striatal synaptosomes and 3H-noradrenaline from cortical synaptosomes in a dose-dependent way. Neither dibutyryl cyclic AMP nor theophylline had any significant effect on either spontaneous or on potassium-evoked 3H-catecholamine release. It is suggested that the effect of papaverine on catecholamine release is not due to its phosphodiesterase inhibitory potency.", "contents": "The effects of dibutyryl cyclic AMP, theophylline and papaverine on the release of 3H-catecholamines from rat brain striatal and cortical synaptosomes. Papaverine enhances the spontaneous release of 3H-dopamine from rat brain striatal synaptosomes and 3H-noradrenaline from cortical synaptosomes in a dose-dependent way. Neither dibutyryl cyclic AMP nor theophylline had any significant effect on either spontaneous or on potassium-evoked 3H-catecholamine release. It is suggested that the effect of papaverine on catecholamine release is not due to its phosphodiesterase inhibitory potency."}
{"id": "PMID:201473", "title": "Effects of 4-aminopyridine on mechanical activity and noradrenaline release in the rat portal vein in vitro.", "content": "4-Aminopyridine (4-AP) increased the spontaneous mechanical activity of the isolated rat portal vein. Since denervation and adrenergic receptor blockade failed to prevent this effect of 4-AP it is suggested that the drug enhances the electrical excitability of the muscle membrane. 4-AP significantly increased the response of the muscle to electrical nerve stimulation in most experiments but had little effect on the response to applied noradrenaline (NA). Both spontaneous and evoked release of 3H-activity, following preincubation in 3H-noradrenaline, were increased in the presence of 4-AP (10(-3) M). The present results with 4-AP can be explained by its known ability to block the transient potassium conductance which accompanies the action potential in excitable tissues.", "contents": "Effects of 4-aminopyridine on mechanical activity and noradrenaline release in the rat portal vein in vitro. 4-Aminopyridine (4-AP) increased the spontaneous mechanical activity of the isolated rat portal vein. Since denervation and adrenergic receptor blockade failed to prevent this effect of 4-AP it is suggested that the drug enhances the electrical excitability of the muscle membrane. 4-AP significantly increased the response of the muscle to electrical nerve stimulation in most experiments but had little effect on the response to applied noradrenaline (NA). Both spontaneous and evoked release of 3H-activity, following preincubation in 3H-noradrenaline, were increased in the presence of 4-AP (10(-3) M). The present results with 4-AP can be explained by its known ability to block the transient potassium conductance which accompanies the action potential in excitable tissues."}
{"id": "PMID:201485", "title": "Potentials in mammalian skeletal muscle from collagenase-treated tissue.", "content": "Transmembrane potentials were recorded from skeletal muscle fibres dissected with the aid of collagenase perfusion. Collagenase treatment had little or no effect on the action or resting potentials.", "contents": "Potentials in mammalian skeletal muscle from collagenase-treated tissue. Transmembrane potentials were recorded from skeletal muscle fibres dissected with the aid of collagenase perfusion. Collagenase treatment had little or no effect on the action or resting potentials."}
{"id": "PMID:201486", "title": "Proposed effects of brain noradrenaline on neuronal activity and cerebral blood flow during REM sleep.", "content": "We propose that the observed increases of both neuronal activity and cerebral blood flow seen throughout the brain during REM sleep may be effects of decreased central noradrenaline release.", "contents": "Proposed effects of brain noradrenaline on neuronal activity and cerebral blood flow during REM sleep. We propose that the observed increases of both neuronal activity and cerebral blood flow seen throughout the brain during REM sleep may be effects of decreased central noradrenaline release."}
{"id": "PMID:201487", "title": "Multiple oncogenesis of neural crest cells by steroids in suckling mice.", "content": "In suckling mice injected with steroids, multiple tumors occurred in the sites where neural crest cells normally are present. It is speculated that the phase of the cell cycle of the neural crest cells may have something to do with its cell surface and cellular phenotypic expression in the system mediated by cyclic AMP.", "contents": "Multiple oncogenesis of neural crest cells by steroids in suckling mice. In suckling mice injected with steroids, multiple tumors occurred in the sites where neural crest cells normally are present. It is speculated that the phase of the cell cycle of the neural crest cells may have something to do with its cell surface and cellular phenotypic expression in the system mediated by cyclic AMP."}
{"id": "PMID:201488", "title": "Effect of dibutyryl cAMP and theophylline on cultured rat embryonic shields.", "content": "Effects of N6, O2 dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) and theophylline (Th) on cultured rat embryonic shields were studied. After addition of db-cAMP to the culture medium, an increase of the weight of explants and of the incidence of the skeletal muscle was observed. Theophylline seems to be ineffective.", "contents": "Effect of dibutyryl cAMP and theophylline on cultured rat embryonic shields. Effects of N6, O2 dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) and theophylline (Th) on cultured rat embryonic shields were studied. After addition of db-cAMP to the culture medium, an increase of the weight of explants and of the incidence of the skeletal muscle was observed. Theophylline seems to be ineffective."}
{"id": "PMID:201504", "title": "From deoxynucleotides to DNA synthesis.", "content": "The deoxyribonucleotides required for DNA synthesis are provided by reduction of ribonucleotides. Our studies aim at an understanding of the interplay between the processes involved in the production of deoxyribonucleotides and in their consumption. The enzyme system reducing ribonucleotides has been characterized in some detail, and its regulatory aspects were investigated with pure enzymes. Knowledge gained in this way made it possible to interfere specifically with the activity of ribonucleotide reductase in intact cells and to study effects on DNA synthesis. In this connection, the replication of polyoma DNA was used as a model that allowed dissection of DNA synthesis into different steps involved in the initiation and elongation processes.", "contents": "From deoxynucleotides to DNA synthesis. The deoxyribonucleotides required for DNA synthesis are provided by reduction of ribonucleotides. Our studies aim at an understanding of the interplay between the processes involved in the production of deoxyribonucleotides and in their consumption. The enzyme system reducing ribonucleotides has been characterized in some detail, and its regulatory aspects were investigated with pure enzymes. Knowledge gained in this way made it possible to interfere specifically with the activity of ribonucleotide reductase in intact cells and to study effects on DNA synthesis. In this connection, the replication of polyoma DNA was used as a model that allowed dissection of DNA synthesis into different steps involved in the initiation and elongation processes."}
{"id": "PMID:201505", "title": "Macrophage-induced reversal of immunosuppression by leukemia viruses.", "content": "Suppression of the humoral immune response by several murine leukemia viruses has been well documented. However, the mechanism of suppressed immunoresponsiveness is not well characterized. Macrophages have been reported to be intimately involved in host-tumor relationships, and were therefore examined for their role in reversing suppression in two leukemia virus-induced tumor models. In vivo studies with the Friend leukemia virus (FL virus) were unsuccessful in demonstrating any role for stimulated peritoneal exudate (PE) cells, rich in macrophages, in restoration of antibody function in leukemic mice. However, in vitro studies with FL virus demonstrated that proteose-peptone stimulated PE cells from normal syngeneic mice in restricted numbers (1-3 x 10(5)), when added to 5 x 10(6) FL virus infected spleen cells, could partially restore immunity. Furthermore, using the Rowson-Parr virus (RP virus) model system it was shown that PE cells from RP virus-infected mice, as well as normal PE cells, were capable of restoring immunocompetence. Neither splenic adherent cells nor lymphoid cells from other tissues, when added to RP virus-infected spleen cells, were able to induce recovery of the immune response. In addition, treatment with antitheta serum plus complement had no effect on the ability of PE cells to restore immunity, implying that macrophages were solely responsible for reversal of immunosuppression. An alteration of antigen \"processing\" or \"focusing\" may be an important mechanism by which recovery of immune competence is achieved.", "contents": "Macrophage-induced reversal of immunosuppression by leukemia viruses. Suppression of the humoral immune response by several murine leukemia viruses has been well documented. However, the mechanism of suppressed immunoresponsiveness is not well characterized. Macrophages have been reported to be intimately involved in host-tumor relationships, and were therefore examined for their role in reversing suppression in two leukemia virus-induced tumor models. In vivo studies with the Friend leukemia virus (FL virus) were unsuccessful in demonstrating any role for stimulated peritoneal exudate (PE) cells, rich in macrophages, in restoration of antibody function in leukemic mice. However, in vitro studies with FL virus demonstrated that proteose-peptone stimulated PE cells from normal syngeneic mice in restricted numbers (1-3 x 10(5)), when added to 5 x 10(6) FL virus infected spleen cells, could partially restore immunity. Furthermore, using the Rowson-Parr virus (RP virus) model system it was shown that PE cells from RP virus-infected mice, as well as normal PE cells, were capable of restoring immunocompetence. Neither splenic adherent cells nor lymphoid cells from other tissues, when added to RP virus-infected spleen cells, were able to induce recovery of the immune response. In addition, treatment with antitheta serum plus complement had no effect on the ability of PE cells to restore immunity, implying that macrophages were solely responsible for reversal of immunosuppression. An alteration of antigen \"processing\" or \"focusing\" may be an important mechanism by which recovery of immune competence is achieved."}
{"id": "PMID:201506", "title": "Effects of aging on the hypothalamic-hypophyseal-gonadal axis in female rats.", "content": "The failure of reproductive function in aged rats could be due to deficiencies at the level of the ovary, pituitary, hypothalamus, or higher brain centers. The classic explanation that the ovary is depleted of follicles does not receive adequate support on the basis of histologic studies of aged ovaries. Basal serum gonadotropin levels change with increasing age in female rats. Serum follicle-stimulating hormone (FSH) levels rise while serum luteinizing hormone (LH) levels fall. Likewise, the characteristic response to castration is markedly altered in aged female rats with a reduced secretion of FSH and a minimal elevation of LH. However, the pituitaires of these animals are still caapable of responding to exogenous LH-releasing hormone with a delayed LH response whose magnitude simulates that seen in younger female animals. With increasing age there is decreased pituitary and/or hypothalamic sensitivity to the feedback action of estradiol. These data are consistent with the postulation that there is an altered hypothalamic-hypophyseal function in aged rats.", "contents": "Effects of aging on the hypothalamic-hypophyseal-gonadal axis in female rats. The failure of reproductive function in aged rats could be due to deficiencies at the level of the ovary, pituitary, hypothalamus, or higher brain centers. The classic explanation that the ovary is depleted of follicles does not receive adequate support on the basis of histologic studies of aged ovaries. Basal serum gonadotropin levels change with increasing age in female rats. Serum follicle-stimulating hormone (FSH) levels rise while serum luteinizing hormone (LH) levels fall. Likewise, the characteristic response to castration is markedly altered in aged female rats with a reduced secretion of FSH and a minimal elevation of LH. However, the pituitaires of these animals are still caapable of responding to exogenous LH-releasing hormone with a delayed LH response whose magnitude simulates that seen in younger female animals. With increasing age there is decreased pituitary and/or hypothalamic sensitivity to the feedback action of estradiol. These data are consistent with the postulation that there is an altered hypothalamic-hypophyseal function in aged rats."}
{"id": "PMID:201508", "title": "[Enzymes of the pentose phosphate pathway in the brains of rats during long-term deprivation of the paradoxical stage of sleep].", "content": "The selective paradoxical sleep (PS) deprivation in rats entailed during first 2 days a drop in activity of glucose-6-phosphatehydrogenase by 80 and 60%, and of 6-phosphogluconatdehydrogenase -- by 20--35 and 40--50% in the brain-stem and the cortex, respectively. Activity of the transketolase decreased by 27--29% on the 2nd day of PS deprivation only. On the 4th day, normalizing of activity of all the enzymes under study except transketolase, was observed in both regions of the brain. The consumption of riboso-5-phosphate by the homogenate and level of phosphoketopentoses formation in it reflected, mainly, the dynamics of transketolase activity changes.", "contents": "[Enzymes of the pentose phosphate pathway in the brains of rats during long-term deprivation of the paradoxical stage of sleep]. The selective paradoxical sleep (PS) deprivation in rats entailed during first 2 days a drop in activity of glucose-6-phosphatehydrogenase by 80 and 60%, and of 6-phosphogluconatdehydrogenase -- by 20--35 and 40--50% in the brain-stem and the cortex, respectively. Activity of the transketolase decreased by 27--29% on the 2nd day of PS deprivation only. On the 4th day, normalizing of activity of all the enzymes under study except transketolase, was observed in both regions of the brain. The consumption of riboso-5-phosphate by the homogenate and level of phosphoketopentoses formation in it reflected, mainly, the dynamics of transketolase activity changes."}
{"id": "PMID:201509", "title": "[Effect of corticotropin and hydrocortisone on the contractility and heat production of skeletal muscles].", "content": "The ACTH was shown to increase whereas hydrocortisone entailed no changes of the muscle contraction amplitude, the duration of the muscle work to fatigue in the regimen of solitary rhythmic contractions being, however, shortened in both bases. The heat production for a unit of the muscle work remained the same after ACTH and decreased after hydrocortisone. The corticotropin increases whereas hydrocortisone decreases the efficiency of the energy substances usage by the working muscles.", "contents": "[Effect of corticotropin and hydrocortisone on the contractility and heat production of skeletal muscles]. The ACTH was shown to increase whereas hydrocortisone entailed no changes of the muscle contraction amplitude, the duration of the muscle work to fatigue in the regimen of solitary rhythmic contractions being, however, shortened in both bases. The heat production for a unit of the muscle work remained the same after ACTH and decreased after hydrocortisone. The corticotropin increases whereas hydrocortisone decreases the efficiency of the energy substances usage by the working muscles."}
{"id": "PMID:201510", "title": "[Studies on the biosynthesis and secretion of parathyroid hormone in monolayer cultures of bovine parathyroid cells (I) (author's transl)].", "content": "We have developed a preparation of monolayer cultures of bovine parathyroid cells in order to elucidate the control mechanism of the biosynthesis and secretion of parathyroid hormone (PTH) at cellular level. Dispersion of parathyroid cells was performed by stirring minced bovine parathyroid tissues in Hanks' BSS containing 0.3 yields to 0.5 percent collagenase at 37 degrees C for 60 min. Dispersed cells were cultured at 37 degrees C in MEM-Hanks' BSS containing 10 percent fetal calf serum and 15 mM HEPES. On the 5th day of the culture, the medium was replaced with 1 percent BSA-MEM-Hanks-HEPES buffer, and the cells were incubated with 3H-leucine or in the media containing various concentrations of calcium, magnesium, PGE1, PGE2 or DBcAMP. At the end of incubation, the cells were detouched and homogenized in 8M urea, 0.2 N HCL and 0.01 M cysteine solution. The isolation of proparathyroid hormone (ProPTH) and PTH was performed through the preparation of TCA-powder followed by CMC column chromatography. PTH in the incubation medium was determined by radioimmunoassay. It was demonstrated that the monolayer cultures of bovine parathyroid cells were synthesizing ProPTH and converting it to PTH. The cultures exhibited linear secretion rates of PTH into the medium. The secretion of PTH was markedly increased by PGE1, PGE2 or DBcAMP in the range of 10(-7) yields to 10(-5)M in the former and 10(-5) yields to 10(-3)M in the latter, while calcium or magnesium changed secretion rate in the range of 0.3 yields to 4.4 mM.", "contents": "[Studies on the biosynthesis and secretion of parathyroid hormone in monolayer cultures of bovine parathyroid cells (I) (author's transl)]. We have developed a preparation of monolayer cultures of bovine parathyroid cells in order to elucidate the control mechanism of the biosynthesis and secretion of parathyroid hormone (PTH) at cellular level. Dispersion of parathyroid cells was performed by stirring minced bovine parathyroid tissues in Hanks' BSS containing 0.3 yields to 0.5 percent collagenase at 37 degrees C for 60 min. Dispersed cells were cultured at 37 degrees C in MEM-Hanks' BSS containing 10 percent fetal calf serum and 15 mM HEPES. On the 5th day of the culture, the medium was replaced with 1 percent BSA-MEM-Hanks-HEPES buffer, and the cells were incubated with 3H-leucine or in the media containing various concentrations of calcium, magnesium, PGE1, PGE2 or DBcAMP. At the end of incubation, the cells were detouched and homogenized in 8M urea, 0.2 N HCL and 0.01 M cysteine solution. The isolation of proparathyroid hormone (ProPTH) and PTH was performed through the preparation of TCA-powder followed by CMC column chromatography. PTH in the incubation medium was determined by radioimmunoassay. It was demonstrated that the monolayer cultures of bovine parathyroid cells were synthesizing ProPTH and converting it to PTH. The cultures exhibited linear secretion rates of PTH into the medium. The secretion of PTH was markedly increased by PGE1, PGE2 or DBcAMP in the range of 10(-7) yields to 10(-5)M in the former and 10(-5) yields to 10(-3)M in the latter, while calcium or magnesium changed secretion rate in the range of 0.3 yields to 4.4 mM."}
{"id": "PMID:201511", "title": "[The effect of calcium on steroidogenesis in isolated human adrenal cells (author's transl)].", "content": "The present experiment was planned to verify the effect of calcium on adenyl cyclase in isolated human adrenal cells. Normal adrenal glands were obtained surgically from patients with primary aldosteronism and advanced breast cancer. Isolated adrenal cells were prepared by the modified Haning's method. They were incubated at 37C under a gas mixture of 95 percent O2: 5 percent CO2 in calcium-free Krebs-Ringer bicarbonate buffer solution containing 0.2 percent glucose and 0.5 percent fatty acid-free bovine serum albumin, to which various doses of CaCl2 or ACTH were added. Thirty minutes later, cyclic-AMP was measured by cyclic-AMP assay kit (The Radio-chemical Center, Amersham). 11-OHCS was estimated fluorometrically by the modified Silber's method after incubation for 2 hours. In the calcium-free incubation medium, productions of 11-OHCS and cyclic-AMP were negligible. In the concentration of 2.54 mM/L of calcium, 11-OHCS production increased with significant difference statistically, while the increase of cyclic-AMP production was not significant. In the concentration of 12.70 mM/L of calcium, however, cyclic-AMP production increased remarkably. When ACTH was added to the incubation medium containing 2.54 mM/L of calcium, productions of 11-OHCS and cyclic-AMP also increased remarkably. These results indicate that adenyl cyclase of human adrenocortical cells is directly stimulated by calcium and suggest that calcium acts as the second messenger of ACTH.", "contents": "[The effect of calcium on steroidogenesis in isolated human adrenal cells (author's transl)]. The present experiment was planned to verify the effect of calcium on adenyl cyclase in isolated human adrenal cells. Normal adrenal glands were obtained surgically from patients with primary aldosteronism and advanced breast cancer. Isolated adrenal cells were prepared by the modified Haning's method. They were incubated at 37C under a gas mixture of 95 percent O2: 5 percent CO2 in calcium-free Krebs-Ringer bicarbonate buffer solution containing 0.2 percent glucose and 0.5 percent fatty acid-free bovine serum albumin, to which various doses of CaCl2 or ACTH were added. Thirty minutes later, cyclic-AMP was measured by cyclic-AMP assay kit (The Radio-chemical Center, Amersham). 11-OHCS was estimated fluorometrically by the modified Silber's method after incubation for 2 hours. In the calcium-free incubation medium, productions of 11-OHCS and cyclic-AMP were negligible. In the concentration of 2.54 mM/L of calcium, 11-OHCS production increased with significant difference statistically, while the increase of cyclic-AMP production was not significant. In the concentration of 12.70 mM/L of calcium, however, cyclic-AMP production increased remarkably. When ACTH was added to the incubation medium containing 2.54 mM/L of calcium, productions of 11-OHCS and cyclic-AMP also increased remarkably. These results indicate that adenyl cyclase of human adrenocortical cells is directly stimulated by calcium and suggest that calcium acts as the second messenger of ACTH."}
{"id": "PMID:201513", "title": "[Secretory regulation and episodic secretion of aldosterone in patients with primary aldosteronism (author's transl)].", "content": "In nine patients with primary aldosteronism (PA), plasma aldosterone was measured in order to evaluate a role of the renin-angiotensin system, ACTH and potassium in the secretion of aldosterone. The circadian rhythm and the episodic secretion were also studied in three patients. The results were as follows: 1) In seven out of nine patients, plasma aldosterone levels (PAL) decreased after the two-hours standing, and it run parallel with plasma cortisol levels (PCL), but not with plasma renin activity (PRA). 2) An intravenous infusion of saline of 2000 ml during four hours failed to suppress PAL in all of five patients and the change of PAL was parallel with that of PCL. 3) PAL decreased markedly after the oral administration of 1 mg of dexamethasone (Dexa), and there was a significantly positive correlation (r = 0.898, p less than 0.01) between basal PAL and the its decrement. 4) Following an intravenous infusion of angiotensin-II at a rate of 0.015 microgram/Kg/min after the pretreatment with Dexa, no significant increase of PAL was observed in any of the five patients. 5) Following a single injection of 0.25 mg of ACTH after the pretreatment with Dexa, PAL rose rapidly, and its peak level was found 60 minutes after the injection. In four out of eight patients this rise was greater than that in the normal subjects. 6) An intravenous infusion of 20 mEq of KCl after the pretreatment with Dexa, produced normal response i.e., an increase of PAL in all seven of the patients. 7) The circadian rhythm and the episodic secretion of PAL in the patients were synchronous with those of PCL throughout twenty four hours.", "contents": "[Secretory regulation and episodic secretion of aldosterone in patients with primary aldosteronism (author's transl)]. In nine patients with primary aldosteronism (PA), plasma aldosterone was measured in order to evaluate a role of the renin-angiotensin system, ACTH and potassium in the secretion of aldosterone. The circadian rhythm and the episodic secretion were also studied in three patients. The results were as follows: 1) In seven out of nine patients, plasma aldosterone levels (PAL) decreased after the two-hours standing, and it run parallel with plasma cortisol levels (PCL), but not with plasma renin activity (PRA). 2) An intravenous infusion of saline of 2000 ml during four hours failed to suppress PAL in all of five patients and the change of PAL was parallel with that of PCL. 3) PAL decreased markedly after the oral administration of 1 mg of dexamethasone (Dexa), and there was a significantly positive correlation (r = 0.898, p less than 0.01) between basal PAL and the its decrement. 4) Following an intravenous infusion of angiotensin-II at a rate of 0.015 microgram/Kg/min after the pretreatment with Dexa, no significant increase of PAL was observed in any of the five patients. 5) Following a single injection of 0.25 mg of ACTH after the pretreatment with Dexa, PAL rose rapidly, and its peak level was found 60 minutes after the injection. In four out of eight patients this rise was greater than that in the normal subjects. 6) An intravenous infusion of 20 mEq of KCl after the pretreatment with Dexa, produced normal response i.e., an increase of PAL in all seven of the patients. 7) The circadian rhythm and the episodic secretion of PAL in the patients were synchronous with those of PCL throughout twenty four hours."}
{"id": "PMID:201514", "title": "[A case of medullary thyroid carcinoma with ectopic ACTH syndrome (author's transl)].", "content": "A 53-year-old male with Cushing's syndrome due to ectopic ACTH production from medullary carcinoma of the thyroid was reported. The clinical course and results of detailed endocrinological studies and immunohistochemical findings about the cancer tissue were described. An abnormally high concentration of calcitonin, ACTH and beta-MSH in both plasma and cancer tissue (thyroid, lymph nodes and liver) were documented by radioimmunoassay. Urinary 17-OHCS was as high as 38.4 mg/day and showed no supression following dexamethasone 8 mg/day administration. ORAL METYRAPONE (3 G/DAY) CAUSED NO RESPONSE IN URINARY 17-OHCS. Parallel increments in plasma calcitonin, ACTH and beta-MSH were observed following calcium and gastrin loading. Total thyroidectomy with modified radical neck dissection caused minimal changes of plasma levels of calcitonin, ACTH and beta-MSH and no improvement in the clinical manifestations of Cushing's syndrome. An aortogram revealed metastatic tumors in the liver. A second operation, total adrenalectomy, resulted in an improvement of the clinical and laboratory findings such as hypokalemia, high blood pressure, muscle atrophy and moon face. Immunofluorescent study showed different distribution patterns in calcitonin- and ACTH-positive cells in the primary focus but similar patterns in the liver metastasis.", "contents": "[A case of medullary thyroid carcinoma with ectopic ACTH syndrome (author's transl)]. A 53-year-old male with Cushing's syndrome due to ectopic ACTH production from medullary carcinoma of the thyroid was reported. The clinical course and results of detailed endocrinological studies and immunohistochemical findings about the cancer tissue were described. An abnormally high concentration of calcitonin, ACTH and beta-MSH in both plasma and cancer tissue (thyroid, lymph nodes and liver) were documented by radioimmunoassay. Urinary 17-OHCS was as high as 38.4 mg/day and showed no supression following dexamethasone 8 mg/day administration. ORAL METYRAPONE (3 G/DAY) CAUSED NO RESPONSE IN URINARY 17-OHCS. Parallel increments in plasma calcitonin, ACTH and beta-MSH were observed following calcium and gastrin loading. Total thyroidectomy with modified radical neck dissection caused minimal changes of plasma levels of calcitonin, ACTH and beta-MSH and no improvement in the clinical manifestations of Cushing's syndrome. An aortogram revealed metastatic tumors in the liver. A second operation, total adrenalectomy, resulted in an improvement of the clinical and laboratory findings such as hypokalemia, high blood pressure, muscle atrophy and moon face. Immunofluorescent study showed different distribution patterns in calcitonin- and ACTH-positive cells in the primary focus but similar patterns in the liver metastasis."}
{"id": "PMID:201515", "title": "Thyroxine secretion by isolated hog thyroid cells: a cyclic AMP independent pathway.", "content": "The release of 131I-labeled thyroxine (T4) from isolated hog thyroid cells was increased 1.5--2-fold by thyrotropin (TSH). Dibutyryl cyclic AMP failed to reproduce this TSH action. In this in vitro system another cell activity, T4 synthesis, was stimulated in an essentially identical fashion by TSH and dibutyryl cyclic AMP (time course of action, dose-response relationship). 3-Isobutyl-1-methylxanthine (IBMX), 0.5 mM, did not alter the basal [131I]T4 release whereas it enhanced the [131I]T4 synthesis. TSH, 60 MU/ml, increased the intracellular cyclic AMP concentration 3-4-fold. Chlorpromazine (5 X 10(-4)M) abolished the TSH stimulation of cyclic AMP accumulation but did not alter the TSH-induced increase in [131I]T4 secretion. It is concluded that the TSH action on [131I]T4 secretion by isolated thyroid cells is not mediated by the adenylate cyclase-cylic AMP system.", "contents": "Thyroxine secretion by isolated hog thyroid cells: a cyclic AMP independent pathway. The release of 131I-labeled thyroxine (T4) from isolated hog thyroid cells was increased 1.5--2-fold by thyrotropin (TSH). Dibutyryl cyclic AMP failed to reproduce this TSH action. In this in vitro system another cell activity, T4 synthesis, was stimulated in an essentially identical fashion by TSH and dibutyryl cyclic AMP (time course of action, dose-response relationship). 3-Isobutyl-1-methylxanthine (IBMX), 0.5 mM, did not alter the basal [131I]T4 release whereas it enhanced the [131I]T4 synthesis. TSH, 60 MU/ml, increased the intracellular cyclic AMP concentration 3-4-fold. Chlorpromazine (5 X 10(-4)M) abolished the TSH stimulation of cyclic AMP accumulation but did not alter the TSH-induced increase in [131I]T4 secretion. It is concluded that the TSH action on [131I]T4 secretion by isolated thyroid cells is not mediated by the adenylate cyclase-cylic AMP system."}
{"id": "PMID:201516", "title": "Inhibitory effects of cyclic AMP on vasopressin release from the rat neural lobe in vitro.", "content": "The basal release of vasopressin from the isolated neural lobe of the rat decreased in the presence of exogenous cAMP, 8Br-cAMP, diB-cAMP, theophylline, SQ 20,009 and RO20-1724. The concentration-related decrease in vasopressin release, in the presence of phosphodiesterase inhibitors, was accompanied by a progressive increase in cAMP concentration in the neural lobe. The findings suggest a local modulation of vasopressin release from the neural lobes.", "contents": "Inhibitory effects of cyclic AMP on vasopressin release from the rat neural lobe in vitro. The basal release of vasopressin from the isolated neural lobe of the rat decreased in the presence of exogenous cAMP, 8Br-cAMP, diB-cAMP, theophylline, SQ 20,009 and RO20-1724. The concentration-related decrease in vasopressin release, in the presence of phosphodiesterase inhibitors, was accompanied by a progressive increase in cAMP concentration in the neural lobe. The findings suggest a local modulation of vasopressin release from the neural lobes."}
{"id": "PMID:201517", "title": "Primary action of steroid hormone at the surface of amphibian oocyte in the induction of germinal vesicle breakdown.", "content": "An insoluble steroid derivative was prepared by the coupling of desoxycorticosterone with aminoethylated agarose beads. When the naked full-grown Xenopus oocytes were incubated in contact with the steroid-bound agarose beads, the dissociation of oocyte nuclei or the initial step in the maturation of amphibian oocyte was induced in 30-100% of total oocytes. The induction did not occur in the oocytes covered with follicle cells and when the naked oocytes were placed apart from the steroid-bound agarose beads in the medium. The above findings confirmed that the oocyte surface was a primary site for this particular steroid action, eliminating the possibility of participation of free steroid artifactually released from the agarose. The 105,000g supernatant fraction of oocytes showed no sign of the presence of steroid receptor. This was not inconsistent with the assumption mentioned above.", "contents": "Primary action of steroid hormone at the surface of amphibian oocyte in the induction of germinal vesicle breakdown. An insoluble steroid derivative was prepared by the coupling of desoxycorticosterone with aminoethylated agarose beads. When the naked full-grown Xenopus oocytes were incubated in contact with the steroid-bound agarose beads, the dissociation of oocyte nuclei or the initial step in the maturation of amphibian oocyte was induced in 30-100% of total oocytes. The induction did not occur in the oocytes covered with follicle cells and when the naked oocytes were placed apart from the steroid-bound agarose beads in the medium. The above findings confirmed that the oocyte surface was a primary site for this particular steroid action, eliminating the possibility of participation of free steroid artifactually released from the agarose. The 105,000g supernatant fraction of oocytes showed no sign of the presence of steroid receptor. This was not inconsistent with the assumption mentioned above."}
{"id": "PMID:201520", "title": "10-years experience with a 28,800 roller bottle plant for FMD vaccine production.", "content": "The roller bottle plant at the Istituto Zooprofilattico of Brescia is described and the following topics are discussed: (1) results of ten years cell and virus culture; (2) critical approach to advantages and disadvantages of applied technology, and (3) FMD vaccine requirements and cell substrate characterization.", "contents": "10-years experience with a 28,800 roller bottle plant for FMD vaccine production. The roller bottle plant at the Istituto Zooprofilattico of Brescia is described and the following topics are discussed: (1) results of ten years cell and virus culture; (2) critical approach to advantages and disadvantages of applied technology, and (3) FMD vaccine requirements and cell substrate characterization."}
{"id": "PMID:201523", "title": "Relative sensitivity of three cell substrates to the Sabin poliovirus strains.", "content": "Poliovirus types 1, 2 and 3 (Sabin strains) were titrated using microtissue culture plates in three different cell substrates: Hep 2C, Vero and MRC-5 human diploid cells. Each type of poliovirus was titrated 60 times. The virus dilutions were inoculated in the three cell substrates and the titres (TCID50/ml) calculated by the Spearman-K\u00e4rber method. The results were analyzed by the U-test (Mann and Whitney procedure) in a Wang 600 computer. For poliovirus type 1 the differences in titres observed between Hep 2C and Vero cells were not statistically significant at p = 0.01, but the differences in titres between Hep 2C and MRC-5 human diploid cells and between Vero and MRC-5 cells were statistically highly significant (p = 0.001). For poliovirus types 2 and 3 the observed differences in titres were highly significant (p = 0.001) between Hep 2C and Vero cells, Hep 2C and MRC-5 and also between Vero and MRC-5 cells, with higher titres on Hep 2C cells. Accordingly with these results Hep 2C and Vero cells showed the same susceptibility to poliovirus type 1. In MCR-5 cells the average titre (G.M.T.) was 1 log10 below the average titres (G.M.T.) from Hep 2C or Vero cells. With poliovirus types 2 and 3 the higher titres were obtained on Hep 2C cells with significant differences to the titres observed in Vero and MRC-5 human diploid cells, which showed less susceptibility.", "contents": "Relative sensitivity of three cell substrates to the Sabin poliovirus strains. Poliovirus types 1, 2 and 3 (Sabin strains) were titrated using microtissue culture plates in three different cell substrates: Hep 2C, Vero and MRC-5 human diploid cells. Each type of poliovirus was titrated 60 times. The virus dilutions were inoculated in the three cell substrates and the titres (TCID50/ml) calculated by the Spearman-K\u00e4rber method. The results were analyzed by the U-test (Mann and Whitney procedure) in a Wang 600 computer. For poliovirus type 1 the differences in titres observed between Hep 2C and Vero cells were not statistically significant at p = 0.01, but the differences in titres between Hep 2C and MRC-5 human diploid cells and between Vero and MRC-5 cells were statistically highly significant (p = 0.001). For poliovirus types 2 and 3 the observed differences in titres were highly significant (p = 0.001) between Hep 2C and Vero cells, Hep 2C and MRC-5 and also between Vero and MRC-5 cells, with higher titres on Hep 2C cells. Accordingly with these results Hep 2C and Vero cells showed the same susceptibility to poliovirus type 1. In MCR-5 cells the average titre (G.M.T.) was 1 log10 below the average titres (G.M.T.) from Hep 2C or Vero cells. With poliovirus types 2 and 3 the higher titres were obtained on Hep 2C cells with significant differences to the titres observed in Vero and MRC-5 human diploid cells, which showed less susceptibility."}
{"id": "PMID:201521", "title": "The contribution of cytochemistry and electron microscopy to the detection of contaminants in the cell material used for the production of virus vaccines.", "content": "For the production of virus vaccine it is essential to use cellular material free of contaminants that could reach the final product. It is also important to check initial tissue for possible inherent infections. Studies on primary culture of chick embryo fibroblasts have shown in several cases that cultures which appeared normal by current cytological methods had a strongly positive reaction when investigated by the Feulgen reaction for nuclear DNA and acridine orange method proving intense RNA synthesis. Comparison of electron microscopic (EM) pictures of cell sections with results obtained from negatively stained preparations of identical cell material after pronase digestion have shown the presence of viruses, thus elucidating the nature of the inclusions. The combined approach of the above-mentioned problem by cytochemical and EM methods can usefully enlarge the rage of tests employed for the definition of cell populations acceptable for virus vaccine production.", "contents": "The contribution of cytochemistry and electron microscopy to the detection of contaminants in the cell material used for the production of virus vaccines. For the production of virus vaccine it is essential to use cellular material free of contaminants that could reach the final product. It is also important to check initial tissue for possible inherent infections. Studies on primary culture of chick embryo fibroblasts have shown in several cases that cultures which appeared normal by current cytological methods had a strongly positive reaction when investigated by the Feulgen reaction for nuclear DNA and acridine orange method proving intense RNA synthesis. Comparison of electron microscopic (EM) pictures of cell sections with results obtained from negatively stained preparations of identical cell material after pronase digestion have shown the presence of viruses, thus elucidating the nature of the inclusions. The combined approach of the above-mentioned problem by cytochemical and EM methods can usefully enlarge the rage of tests employed for the definition of cell populations acceptable for virus vaccine production."}
{"id": "PMID:201522", "title": "Replication of poliovirus (LSc 2 ab) in perfused cultures of MRC-5 diploid cells.", "content": "Application of a new perfusion culture system to the propagation of poliovirus type 1 (LSc 2 ab) in MRC-5 cells is described. Virus production was compared in perfused and stationary cultures of cells at the 26th to 30th population doubling. Yield of virus per cell and unit growth surface area were found to be consistently higher in the perfused system by factors of three to five fold respectively. The influence of experimental conditions on these results and the potential of perfusion for large scale vaccine manufacture are discussed.", "contents": "Replication of poliovirus (LSc 2 ab) in perfused cultures of MRC-5 diploid cells. Application of a new perfusion culture system to the propagation of poliovirus type 1 (LSc 2 ab) in MRC-5 cells is described. Virus production was compared in perfused and stationary cultures of cells at the 26th to 30th population doubling. Yield of virus per cell and unit growth surface area were found to be consistently higher in the perfused system by factors of three to five fold respectively. The influence of experimental conditions on these results and the potential of perfusion for large scale vaccine manufacture are discussed."}
{"id": "PMID:201526", "title": "Cellular changes in primary rabbit kidney cells resembling those caused by certain viruses.", "content": "Changes suggestive of being caused by a virus have recently been observed in primary rabbit kidney cells. In their nature and development they resembled those of parvoviruses. The changes were found in cultures from rabbits from various sources within and outside The Netherlands. If the changes are caused by a viral agent, this agent is most probably of rabbit origin, as exogenous infection, for example through trypsin, could almost certainly be excluded. However, no virus has yet been isolated nor could particles be made visible by electron microscopy in affected cells. Hemagglutination could not be demonstrated nor could antibody in rabbits. The possible nature of these changes will be discussed.", "contents": "Cellular changes in primary rabbit kidney cells resembling those caused by certain viruses. Changes suggestive of being caused by a virus have recently been observed in primary rabbit kidney cells. In their nature and development they resembled those of parvoviruses. The changes were found in cultures from rabbits from various sources within and outside The Netherlands. If the changes are caused by a viral agent, this agent is most probably of rabbit origin, as exogenous infection, for example through trypsin, could almost certainly be excluded. However, no virus has yet been isolated nor could particles be made visible by electron microscopy in affected cells. Hemagglutination could not be demonstrated nor could antibody in rabbits. The possible nature of these changes will be discussed."}
{"id": "PMID:201530", "title": "Lipolysis and cyclic AMP levels in epididymal adipose tissue of obese-hyperglycaemic mice.", "content": "Glycerol release from epididymal fat fragments of young adult (3-month old) ob/ob mice was three times lower than normal, on a tissue weight basis. Dose-response curves in response to isoproterenol and ACTH-(1--24) indicated that the capacity of the lipolytic process was reduced. However, the sensitivity to both hormones was normal, i.e. greater for ACTH than for isoproterenol. The burst of cyclic AMP observed at 7 minutes was affected even more than the lipolytic capacity in adipose tissue from obese mice. This was already observed in 1-month old animals, i.e. at a time when total body weight was still normal. It is concluded that the adenylate cyclase system is defective in adipose tissue of ob/ob mice. Besides, glucagon, vasoactive intestinal polypeptide, and secretin failed to stimulate glycerol release and cyclic AMP accumulation in both ob/ob, ob+/ob+, and HA-ICR mice, suggesting that mouse adipose tissue does not possess receptors for this group of hormones.", "contents": "Lipolysis and cyclic AMP levels in epididymal adipose tissue of obese-hyperglycaemic mice. Glycerol release from epididymal fat fragments of young adult (3-month old) ob/ob mice was three times lower than normal, on a tissue weight basis. Dose-response curves in response to isoproterenol and ACTH-(1--24) indicated that the capacity of the lipolytic process was reduced. However, the sensitivity to both hormones was normal, i.e. greater for ACTH than for isoproterenol. The burst of cyclic AMP observed at 7 minutes was affected even more than the lipolytic capacity in adipose tissue from obese mice. This was already observed in 1-month old animals, i.e. at a time when total body weight was still normal. It is concluded that the adenylate cyclase system is defective in adipose tissue of ob/ob mice. Besides, glucagon, vasoactive intestinal polypeptide, and secretin failed to stimulate glycerol release and cyclic AMP accumulation in both ob/ob, ob+/ob+, and HA-ICR mice, suggesting that mouse adipose tissue does not possess receptors for this group of hormones."}
{"id": "PMID:201525", "title": "Cytomegalovirus vaccine prepared in WI-38.", "content": "Human fibroblasts are the only cells that regularly produce cytomegalovirus of adapted laboratory strains and release fair amounts of cell free virus. One such strain, Towne, was adapted to WI-38 and could release 10(6) to 10(7) p.f.u. per ml tissue culture fluid. The maximum cell-free virus is released at 5-7 days after infection, when cytopathic effect has reached a peak. The virus harvest must be combined with stabilizer rapidly and rapidly lyophilized or frozen, for the virus is unstable even at 4 degrees C. With regard to control, cytomegalovirus is poorly neutralized by antibody-containing serum, and complement is required for maxium neutralization. Frequent addition of fresh antiserum may be necessary to keep cytomegalovirus from replicating in cells inoculated to detect other viruses. Another special problem is the putative association of oncogenicity with herpes group viruses. Tests must be done in newborn hamsters to show that live or inactivated virus does not cause tumors. Towne vaccine tested in man has produced asymptomatic infection with antibody response. No urine excretion has been observed, and antibodies persist for at least 2 years.", "contents": "Cytomegalovirus vaccine prepared in WI-38. Human fibroblasts are the only cells that regularly produce cytomegalovirus of adapted laboratory strains and release fair amounts of cell free virus. One such strain, Towne, was adapted to WI-38 and could release 10(6) to 10(7) p.f.u. per ml tissue culture fluid. The maximum cell-free virus is released at 5-7 days after infection, when cytopathic effect has reached a peak. The virus harvest must be combined with stabilizer rapidly and rapidly lyophilized or frozen, for the virus is unstable even at 4 degrees C. With regard to control, cytomegalovirus is poorly neutralized by antibody-containing serum, and complement is required for maxium neutralization. Frequent addition of fresh antiserum may be necessary to keep cytomegalovirus from replicating in cells inoculated to detect other viruses. Another special problem is the putative association of oncogenicity with herpes group viruses. Tests must be done in newborn hamsters to show that live or inactivated virus does not cause tumors. Towne vaccine tested in man has produced asymptomatic infection with antibody response. No urine excretion has been observed, and antibodies persist for at least 2 years."}
{"id": "PMID:201528", "title": "Use of polyethyleneglycol-treated serum for animal cell cultures.", "content": "Although many proteins will be removed from sera by precipitation with 10% polyethyleneglycol (PEG) the growth-promoting properties of such PEG-treated sera for many cell lines and cell strains are hardly reduced. Among the precipitated proteins are the macroglobulins which are difficult to remove from cell cultures and which may cause allergic reactions if incorporated into vaccines. The gammaglobulins are removed in this way as well. If the sera are contaminated with viruses or phages the titres will be reduced by approximately 4 logs and thus the incidence of virus contamination will be reduced by the PEG-treatment. For foot-and-mouth Disease (FMD) vaccine production PEG-treated sera from vaccinated cattle were applied for cell and virus cultivation. The virus obtained was subsequently precipitated with PEG and collected by filter-aid filtration. A concentrated virus product was obtained, which was practically devoid of serum proteins.", "contents": "Use of polyethyleneglycol-treated serum for animal cell cultures. Although many proteins will be removed from sera by precipitation with 10% polyethyleneglycol (PEG) the growth-promoting properties of such PEG-treated sera for many cell lines and cell strains are hardly reduced. Among the precipitated proteins are the macroglobulins which are difficult to remove from cell cultures and which may cause allergic reactions if incorporated into vaccines. The gammaglobulins are removed in this way as well. If the sera are contaminated with viruses or phages the titres will be reduced by approximately 4 logs and thus the incidence of virus contamination will be reduced by the PEG-treatment. For foot-and-mouth Disease (FMD) vaccine production PEG-treated sera from vaccinated cattle were applied for cell and virus cultivation. The virus obtained was subsequently precipitated with PEG and collected by filter-aid filtration. A concentrated virus product was obtained, which was practically devoid of serum proteins."}
{"id": "PMID:201527", "title": "Characterization of monolayer cultures of type II alveolar pneumonocytes that produce pulmonary surfactant in vitro.", "content": "In lung, type II cells are the site of synthesis of phosphatidylcholine (PC), a major component of pulmonary surfactant. Clonal culture methods permit isolation of an epithelial cell strain (L-2) derived from type II cells of intact rat lung capable of active PC production in vitro. Isotopic labeling of these monolayer cultures show that the choline incorporation pathway is the predominant biosynthetic route for PC production. This same pathway is utilized for PC production in whole lung. Three enzymes of this pathway are readily detected in L-2 cells. Determination of specific enzyme activity in monolayers and whole lung indicate that clonally derived L-2 cells are enriched in choline kinase (10-fold), cholinephosphate cytidyl transferase (10-fold) and cholinephosphotransferase activity (5-fold). Our second approach was to develop an in vitro system in which cellular inter-relationships and cell to cell contacts present in whole lung are maintained. This organotypic system is formed by reaggregation of monodispersed fetal rat lung cells into alveolar-like structures (ALS). The ALS are comprised primarily of type II cells as evidenced by the presence of osmiophilic lamellar bodies in the cells. Biosynthesis of these lamellar bodies occurs de novo and type II cells in the ALS continue to synthesize lamellar bodies. Both systems permit study of a variety of agents of pulmonary surfactant production in vitro.", "contents": "Characterization of monolayer cultures of type II alveolar pneumonocytes that produce pulmonary surfactant in vitro. In lung, type II cells are the site of synthesis of phosphatidylcholine (PC), a major component of pulmonary surfactant. Clonal culture methods permit isolation of an epithelial cell strain (L-2) derived from type II cells of intact rat lung capable of active PC production in vitro. Isotopic labeling of these monolayer cultures show that the choline incorporation pathway is the predominant biosynthetic route for PC production. This same pathway is utilized for PC production in whole lung. Three enzymes of this pathway are readily detected in L-2 cells. Determination of specific enzyme activity in monolayers and whole lung indicate that clonally derived L-2 cells are enriched in choline kinase (10-fold), cholinephosphate cytidyl transferase (10-fold) and cholinephosphotransferase activity (5-fold). Our second approach was to develop an in vitro system in which cellular inter-relationships and cell to cell contacts present in whole lung are maintained. This organotypic system is formed by reaggregation of monodispersed fetal rat lung cells into alveolar-like structures (ALS). The ALS are comprised primarily of type II cells as evidenced by the presence of osmiophilic lamellar bodies in the cells. Biosynthesis of these lamellar bodies occurs de novo and type II cells in the ALS continue to synthesize lamellar bodies. Both systems permit study of a variety of agents of pulmonary surfactant production in vitro."}
{"id": "PMID:201533", "title": "Analyses of stage-specific multiple forms of lactate dehydrogenase and of cytochrome c during spermatogenesis in the mouse.", "content": "Spermatogenesis is a programmed developmental process characterized by the inactivation of certain genes and the activation of other, testis-specific genes. Synthesis of unique gene products such as LDH-C4 and cytochrome ct occurs only at precise stage of germ cell formation. The developmental sequences of gene activation for these proteins was observed by immunohistochemical procedures. LDH-C4 is first detectable during mid-pachytene of the primary spermatocyte. The C subunits appear to be uniformly distributed throughout the cytoplasm of the spermatocyte. The mid-pachytene stage also marks the first appearance of cytochrome ct. The association of this electron transport protein with spermatocyte mitochondria is reflected in a granular fluorescence of specific antibody-treated sections of testis. Neither the C subunit of LDH, nor cytochrome ct appear in leptotene or early pachytene primary spermatocytes. These analyses indicate that there is stage-specific protein synthesis in the primary spermatocyte which is characterized by differential activation of the LDH-C locus and of the gene coding for cytochrome ct.", "contents": "Analyses of stage-specific multiple forms of lactate dehydrogenase and of cytochrome c during spermatogenesis in the mouse. Spermatogenesis is a programmed developmental process characterized by the inactivation of certain genes and the activation of other, testis-specific genes. Synthesis of unique gene products such as LDH-C4 and cytochrome ct occurs only at precise stage of germ cell formation. The developmental sequences of gene activation for these proteins was observed by immunohistochemical procedures. LDH-C4 is first detectable during mid-pachytene of the primary spermatocyte. The C subunits appear to be uniformly distributed throughout the cytoplasm of the spermatocyte. The mid-pachytene stage also marks the first appearance of cytochrome ct. The association of this electron transport protein with spermatocyte mitochondria is reflected in a granular fluorescence of specific antibody-treated sections of testis. Neither the C subunit of LDH, nor cytochrome ct appear in leptotene or early pachytene primary spermatocytes. These analyses indicate that there is stage-specific protein synthesis in the primary spermatocyte which is characterized by differential activation of the LDH-C locus and of the gene coding for cytochrome ct."}
{"id": "PMID:201534", "title": "Combination chemotherapy of 6-thioguanine with various antitumor agents against murine leukemia L-1210.", "content": "Antitumor activity of 6-thioguanine against L-1210 leukemia was studied in combination with various antitumor agents in clinical stages, such as mitomycin-C, carbazilquinone, cyclophosphamide, 3,3'-dimesyloxydipropylamine tosylate (864T), 4-hydroperoxyisophosphamide, and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chlorethyl)-1-nitrosourea hydrochloride (ACNU). The combination treatments with 6-thioguanine and each of six agents, especially with ACNU, showed a distinct therapeutic effect against the early L-1210 leukemia at dosage levels not producing any significant antitumor activity with each agent alone (ip-ip). The excellent antitumor activity of the combination of 6-thioguanine with ACNU was also proved in various sites of tumor inoculation and routes of drug administration systems, i.e., ip-iv, iv-ip, and iv-iv systems. Moreover, the effectiveness of the combination of these two drugs was clearly shown against advanced L-1210 leukemia which was refractory to each agent alone.", "contents": "Combination chemotherapy of 6-thioguanine with various antitumor agents against murine leukemia L-1210. Antitumor activity of 6-thioguanine against L-1210 leukemia was studied in combination with various antitumor agents in clinical stages, such as mitomycin-C, carbazilquinone, cyclophosphamide, 3,3'-dimesyloxydipropylamine tosylate (864T), 4-hydroperoxyisophosphamide, and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chlorethyl)-1-nitrosourea hydrochloride (ACNU). The combination treatments with 6-thioguanine and each of six agents, especially with ACNU, showed a distinct therapeutic effect against the early L-1210 leukemia at dosage levels not producing any significant antitumor activity with each agent alone (ip-ip). The excellent antitumor activity of the combination of 6-thioguanine with ACNU was also proved in various sites of tumor inoculation and routes of drug administration systems, i.e., ip-iv, iv-ip, and iv-iv systems. Moreover, the effectiveness of the combination of these two drugs was clearly shown against advanced L-1210 leukemia which was refractory to each agent alone."}
{"id": "PMID:201535", "title": "Antitumor effect of 1,1'-polymethylene-bis (1-nitrosourea) and related compounds.", "content": "Polymethylene-bis(1-nitrosourea), polymethylene-bis(1-nitroso-3-nitroguanidine), and polymethylene-bis(1-nitroso-p-toluenesulfonamide) derivatives were tested for antitumor effect against rat ascites hepatoma AH-13 and mouse leukemia L-1210. Bisnitrosoureas were effective against AH-13 and L-1210, bisnitrosoguanidines were effective against AH-13 alone, and bisnitrosotoluene-sulfonamides were ineffective against both tumor lines. Of all these compounds, 1,1'-ethylene-bis(1-nitrosourea) (EBNU) was the most effective. The antitumor effect of EBNU was compared with that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Intraperitoneal administration of EBNU according to the schedule, day 1, days 1 and 5, and days 1, 5, and 9 after intraperitoneal inoculation of L-1210 showed marked prolongation of host survival, although the effective doses used were a few times higher than those used in BCNU to obtain a similar effect. The minimum effective dose (MED) of EBNU on AH-13 cells was estimated as 1 mg/kg, which was 10 times less than that of BCNU, suggesting that EBNU was more effective than BCNU against AH-13.", "contents": "Antitumor effect of 1,1'-polymethylene-bis (1-nitrosourea) and related compounds. Polymethylene-bis(1-nitrosourea), polymethylene-bis(1-nitroso-3-nitroguanidine), and polymethylene-bis(1-nitroso-p-toluenesulfonamide) derivatives were tested for antitumor effect against rat ascites hepatoma AH-13 and mouse leukemia L-1210. Bisnitrosoureas were effective against AH-13 and L-1210, bisnitrosoguanidines were effective against AH-13 alone, and bisnitrosotoluene-sulfonamides were ineffective against both tumor lines. Of all these compounds, 1,1'-ethylene-bis(1-nitrosourea) (EBNU) was the most effective. The antitumor effect of EBNU was compared with that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Intraperitoneal administration of EBNU according to the schedule, day 1, days 1 and 5, and days 1, 5, and 9 after intraperitoneal inoculation of L-1210 showed marked prolongation of host survival, although the effective doses used were a few times higher than those used in BCNU to obtain a similar effect. The minimum effective dose (MED) of EBNU on AH-13 cells was estimated as 1 mg/kg, which was 10 times less than that of BCNU, suggesting that EBNU was more effective than BCNU against AH-13."}
{"id": "PMID:201536", "title": "Role of leucocytes in ascites in the production of factor(s) stimulating differentiation of mouse myeloid leukemia cells.", "content": "Although the ascitic fluid of animals bearing various tumors and that of mice induced by complete Freund's adjuvant had high activity for inducing differentiation of myeloid leukemic cell line (M1) from an SL mouse to macrophages and granulocyte-like cells, the activity in the ascitic fluid of syngeneic mice bearing the M1 cells was markedly reduced. Macrophages and granulocytes were abundant in the active ascites of animals bearing tumors (8 to 12% of the total ascites cells) while in the ascites of syngeneic mice bearing the M1 cells they were not (0.1 to 0.7% of the total ascites cells). Appearance of lymphocytes in the ascites of both types was not significantly different. Although the conditioned media of the Ehrlich tumor cells, M1 cells, and whole ascites cells with the M1 cells were not active in inducing differentiation of the M1 cells, the conditioned media of all the ascites cells with Ehrlich tumor cells and those of peritoneal macrophages and granulocytes in mice did show a high activity. These results indicate that the peritoneal macrophages and granulocytes in the ascites are responsible for the production of factors stimulating differentiation of the M1 cells.", "contents": "Role of leucocytes in ascites in the production of factor(s) stimulating differentiation of mouse myeloid leukemia cells. Although the ascitic fluid of animals bearing various tumors and that of mice induced by complete Freund's adjuvant had high activity for inducing differentiation of myeloid leukemic cell line (M1) from an SL mouse to macrophages and granulocyte-like cells, the activity in the ascitic fluid of syngeneic mice bearing the M1 cells was markedly reduced. Macrophages and granulocytes were abundant in the active ascites of animals bearing tumors (8 to 12% of the total ascites cells) while in the ascites of syngeneic mice bearing the M1 cells they were not (0.1 to 0.7% of the total ascites cells). Appearance of lymphocytes in the ascites of both types was not significantly different. Although the conditioned media of the Ehrlich tumor cells, M1 cells, and whole ascites cells with the M1 cells were not active in inducing differentiation of the M1 cells, the conditioned media of all the ascites cells with Ehrlich tumor cells and those of peritoneal macrophages and granulocytes in mice did show a high activity. These results indicate that the peritoneal macrophages and granulocytes in the ascites are responsible for the production of factors stimulating differentiation of the M1 cells."}
{"id": "PMID:201537", "title": "Studies on tumors produced by cells transformed with herpes simplex virus type 2.", "content": "Biological, histological, and ultrastructural studies were made on tumors produced in weanling hamsters inoculated with hamster embryo fibroblasts (HEF) transformed by herpes simplex virus type 2 or with cultured cells (tumor cell lines T1 and T2) derived from the tumor tissues. The malignancy of transformants increased through passages in vitro and in vivo. Histologically, two tumor cells lines (155-4T1 and U-15T1) produced fibrosarcomas and one (U-26T1) produced lesions resembling \"malignant fibrous histiocytomas.\" Ultrastructurally, fibrosarcomas produced by 155-4T1 and U-15T1 consisted mainly of fibroblast-like cells with extracellular collagen fibers, whereas malignant fibrous histiocytoma-like lesions produced by U-26T1 consisted of undifferentiated cells, multinuclear giant cells, histiocyte-like cells, and fibroblast-like cells. Frequently, various kinds of \"nuclear bodies\" were found in the nuclei of tumor cells. Several herpes virus-like particles (120 approximately 140 nm in diameter) were detected in some nuclei of undifferentiated tumor cells produced by U-26T1.", "contents": "Studies on tumors produced by cells transformed with herpes simplex virus type 2. Biological, histological, and ultrastructural studies were made on tumors produced in weanling hamsters inoculated with hamster embryo fibroblasts (HEF) transformed by herpes simplex virus type 2 or with cultured cells (tumor cell lines T1 and T2) derived from the tumor tissues. The malignancy of transformants increased through passages in vitro and in vivo. Histologically, two tumor cells lines (155-4T1 and U-15T1) produced fibrosarcomas and one (U-26T1) produced lesions resembling \"malignant fibrous histiocytomas.\" Ultrastructurally, fibrosarcomas produced by 155-4T1 and U-15T1 consisted mainly of fibroblast-like cells with extracellular collagen fibers, whereas malignant fibrous histiocytoma-like lesions produced by U-26T1 consisted of undifferentiated cells, multinuclear giant cells, histiocyte-like cells, and fibroblast-like cells. Frequently, various kinds of \"nuclear bodies\" were found in the nuclei of tumor cells. Several herpes virus-like particles (120 approximately 140 nm in diameter) were detected in some nuclei of undifferentiated tumor cells produced by U-26T1."}
{"id": "PMID:201538", "title": "Isozyme patterns of branched-chain amino acid transaminase in human tissues and tumors.", "content": "The isozymes (enzymes I and III) of branched-chain amino acid transaminase (EC 2.6.1.42) from various human tissues were separated by DEAE-cellulose column chromatography. Their distributions were found to be considerably different from those in rat tissues reported before. In rats, all tissues examined contained enzyme I and in addition enzyme II was found in the liver and enzyme III in the brain, ovary, and placenta. In humans, however, enzyme II was not found in any tissues examined including the liver, and enzyme III was found in many other tissues besides brain, ovary, and placenta. All normal human tissues except the lung, ovary, and brain contain less enzyme III than enzyme I. Various human cancers of the liver, kidney, stomach, pancreas, and uterus showed significantly higher ratios of enzyme III to enzyme I than those of the corresponding normal tissues. Fetal liver and kidney also contained much higher concentrations of enzyme III than adult liver and kidney. These findings suggest that change of the isozyme pattern of this enzyme in cancer is similar in humans and rats, and that cancer tissues tend to express more immature phenotypes than normal tissues. Enzymes I and III of human tissues showed the same substrate specificities for valine, leucine, and isoleucine, and these amino acids competed for the active site of the enzyme. Thus the hereditary diseases, hypervalinemia and hyperisoleucine-leucinemia, may be due to genetic alteration of the enzyme protein, resulting in change of its substrate specificity.", "contents": "Isozyme patterns of branched-chain amino acid transaminase in human tissues and tumors. The isozymes (enzymes I and III) of branched-chain amino acid transaminase (EC 2.6.1.42) from various human tissues were separated by DEAE-cellulose column chromatography. Their distributions were found to be considerably different from those in rat tissues reported before. In rats, all tissues examined contained enzyme I and in addition enzyme II was found in the liver and enzyme III in the brain, ovary, and placenta. In humans, however, enzyme II was not found in any tissues examined including the liver, and enzyme III was found in many other tissues besides brain, ovary, and placenta. All normal human tissues except the lung, ovary, and brain contain less enzyme III than enzyme I. Various human cancers of the liver, kidney, stomach, pancreas, and uterus showed significantly higher ratios of enzyme III to enzyme I than those of the corresponding normal tissues. Fetal liver and kidney also contained much higher concentrations of enzyme III than adult liver and kidney. These findings suggest that change of the isozyme pattern of this enzyme in cancer is similar in humans and rats, and that cancer tissues tend to express more immature phenotypes than normal tissues. Enzymes I and III of human tissues showed the same substrate specificities for valine, leucine, and isoleucine, and these amino acids competed for the active site of the enzyme. Thus the hereditary diseases, hypervalinemia and hyperisoleucine-leucinemia, may be due to genetic alteration of the enzyme protein, resulting in change of its substrate specificity."}
{"id": "PMID:201539", "title": "Properties of a transposon conferring resistance to penicillins and streptomycin.", "content": "R938 carries a transposon (TAbeta) of approximate molecular weight 9.5 Megadaltons (Mdal, 10(6) daltons). This contains genes for a beta lactamase of type TEM-1 and for streptomycin phosphatransferase (SPT). There is a ten-fold difference in the efficiency of transposition in different strains of E. coli K12.", "contents": "Properties of a transposon conferring resistance to penicillins and streptomycin. R938 carries a transposon (TAbeta) of approximate molecular weight 9.5 Megadaltons (Mdal, 10(6) daltons). This contains genes for a beta lactamase of type TEM-1 and for streptomycin phosphatransferase (SPT). There is a ten-fold difference in the efficiency of transposition in different strains of E. coli K12."}
{"id": "PMID:201540", "title": "Chromatin transcription. I. Quantitative determination of gene-specific RNA by use of bacterial plasmids containing the eukaryotic DNA sequence of viral DNA.", "content": "Specific gene transcription from chromatin has been examined in two different systems by using direct measurement of specific sequences by hybridization with excess DNA probe. An improved procedure has been used for hybridization of DNA immobilized on filters. This procedure is sensitive to less than one part in 10(5). Polyoma RNA sequences were detected a level of 0.004% in the overall transcript from chromatin of ts-a-transformed 3T3 fibroblasts. By the use of constructed plasmid DNA carrying rabbit globin sequences, globin RNA was titrated in the RNA transcribed from chromatin of bone marrow cells. Its relative frequency was 0.01%. Results obtained with this new approach confirm that DNA in chromatin is not randomly transcribed. They further illustrate that a reproducible assay system is now available for studying control elements active on gene expression at the transcriptional level, taking advantage of the constructed plasmids containing eukaryotic gene DNA fragments.", "contents": "Chromatin transcription. I. Quantitative determination of gene-specific RNA by use of bacterial plasmids containing the eukaryotic DNA sequence of viral DNA. Specific gene transcription from chromatin has been examined in two different systems by using direct measurement of specific sequences by hybridization with excess DNA probe. An improved procedure has been used for hybridization of DNA immobilized on filters. This procedure is sensitive to less than one part in 10(5). Polyoma RNA sequences were detected a level of 0.004% in the overall transcript from chromatin of ts-a-transformed 3T3 fibroblasts. By the use of constructed plasmid DNA carrying rabbit globin sequences, globin RNA was titrated in the RNA transcribed from chromatin of bone marrow cells. Its relative frequency was 0.01%. Results obtained with this new approach confirm that DNA in chromatin is not randomly transcribed. They further illustrate that a reproducible assay system is now available for studying control elements active on gene expression at the transcriptional level, taking advantage of the constructed plasmids containing eukaryotic gene DNA fragments."}
{"id": "PMID:201542", "title": "The influence of dihydroergotoxine mesylate on the low-Km phosphodiesterase of cat and rat brain in vitro.", "content": "Dihydroergotoxine mesylate (DHET; active substance of Hydergine) was shown to be a stronger inhibitor of the low-Km than of the high-Km phosphodiestrase (PE) in cat and rat brain homogenates. The inhibition due to DHET was greater when a purified low-Km PE preparation originating from a sonicated pellet (100,000 g) of rat brain tissue was used. The drug alters the kinetic properties of the enzyme, producing a lowering of the negative cooperativity effect. This kind of PE inhibition is of particular importance at normal cellular cAMP levels, but does not interfere with cAMP production by hormonal stimulation.", "contents": "The influence of dihydroergotoxine mesylate on the low-Km phosphodiesterase of cat and rat brain in vitro. Dihydroergotoxine mesylate (DHET; active substance of Hydergine) was shown to be a stronger inhibitor of the low-Km than of the high-Km phosphodiestrase (PE) in cat and rat brain homogenates. The inhibition due to DHET was greater when a purified low-Km PE preparation originating from a sonicated pellet (100,000 g) of rat brain tissue was used. The drug alters the kinetic properties of the enzyme, producing a lowering of the negative cooperativity effect. This kind of PE inhibition is of particular importance at normal cellular cAMP levels, but does not interfere with cAMP production by hormonal stimulation."}
{"id": "PMID:201543", "title": "Dopamine-mimetic activity of ergot derivatives, as measured by the production of cyclic AMP in isolated retinae of the rabbit.", "content": "The effects of several ergot alkaloid derivatives on the concentration of cyclic AMP in intact rabbit retinae were investigated in vitro. All compounds were found to be potent inducers of cyclic AMP production, half-maximal stimulation being obtained at 10(-6)M, and maximal stimulation at 10(-4)M concentrations. The range of effective concentrations was very well comparable with that of dopamine (or apomorphine) in the same experimental conditions. Furthermore, the accumulation of cyclic AMP induced by the ergot derivatives was blocked by fluphenazine, at 10(-4)-5 X 10(-4)M, or lithium, at 5 X 10(-2)M concentrations. Both antipsychotic drugs were found to be very potent inhibitors of dopamine-(or apomorphine-) induced production of cyclic AMP in the same preparation. A potential dopamine-mimetic activity of ergot derivatives (or of other dopamine-like drugs) can be specifically tested on isolated rabbit retinae in vitro, either before undertaking experiments in vivo or in correlation with behavioural studies.", "contents": "Dopamine-mimetic activity of ergot derivatives, as measured by the production of cyclic AMP in isolated retinae of the rabbit. The effects of several ergot alkaloid derivatives on the concentration of cyclic AMP in intact rabbit retinae were investigated in vitro. All compounds were found to be potent inducers of cyclic AMP production, half-maximal stimulation being obtained at 10(-6)M, and maximal stimulation at 10(-4)M concentrations. The range of effective concentrations was very well comparable with that of dopamine (or apomorphine) in the same experimental conditions. Furthermore, the accumulation of cyclic AMP induced by the ergot derivatives was blocked by fluphenazine, at 10(-4)-5 X 10(-4)M, or lithium, at 5 X 10(-2)M concentrations. Both antipsychotic drugs were found to be very potent inhibitors of dopamine-(or apomorphine-) induced production of cyclic AMP in the same preparation. A potential dopamine-mimetic activity of ergot derivatives (or of other dopamine-like drugs) can be specifically tested on isolated rabbit retinae in vitro, either before undertaking experiments in vivo or in correlation with behavioural studies."}
{"id": "PMID:201544", "title": "Effect of dihydroergotoxine on cyclic-AMP-generating systems in rat cerebral cortex slices.", "content": "In slices of rat cerebral cortex, cyclic-AMP formation is stimulated in response to added noradrenaline (NA), isoproterenol (ISP) or adenosine. The effect of ISP could be antagonized only by the selective beta-adrenoceptor-blocking agent pindolol, whereas the stimulating effect of NA could be antagonized by both alpha- and beta-adrenoceptor-blocking agents. Dihydroergotoxine (DHET) at low concentrations (10(-8)M) antagonized the stimulating effect of NA but not of ISP or adenosine, suggesting that this substance has a high affinity for central alpha-adrenoceptors. We could also show that DHET is accumulated in rat cerebral cortex after repeated oral application. In slices of cortex obtained from rats after treatment with DHET for 3 and 6 weeks, but not after 1 week, NA had a significant lower effect on cyclic-AMP formation than in slices from corresponding controls.", "contents": "Effect of dihydroergotoxine on cyclic-AMP-generating systems in rat cerebral cortex slices. In slices of rat cerebral cortex, cyclic-AMP formation is stimulated in response to added noradrenaline (NA), isoproterenol (ISP) or adenosine. The effect of ISP could be antagonized only by the selective beta-adrenoceptor-blocking agent pindolol, whereas the stimulating effect of NA could be antagonized by both alpha- and beta-adrenoceptor-blocking agents. Dihydroergotoxine (DHET) at low concentrations (10(-8)M) antagonized the stimulating effect of NA but not of ISP or adenosine, suggesting that this substance has a high affinity for central alpha-adrenoceptors. We could also show that DHET is accumulated in rat cerebral cortex after repeated oral application. In slices of cortex obtained from rats after treatment with DHET for 3 and 6 weeks, but not after 1 week, NA had a significant lower effect on cyclic-AMP formation than in slices from corresponding controls."}
{"id": "PMID:201550", "title": "Abnormal regulation of adrenal function in rats with streptozotocin diabetes.", "content": "The factors that control adrenal steroid secretion and metabolism were investigated in rats made diabetic with Streptozotocin (65 mg/kg) and used one month after treatment. Diabetic animals possessed high resting levels of plasma corticosterone accompanied by adrenal hypertrophy; the showed an increased response to the stress of i.p. cold water injection. Moreover, the pituitaries of diabetic rats seemed to be releasing ACTH continuously and not storing it. Upon adrenal inhibition with Aminoglutethimide the expected increase in adrenal cholesterol and weight was of a smaller magnitude than in controls. The activity of liver enzymes that reduce ring A of corticosterone showed decreased activity in diabetics, which suggests that more corticosterone rather than its inactive metabolites were available to--but not able to suppress--the steroid feedback sites. The half-life of corticosterone in blood was similar in diabetes and controls. These results suggest that (a) diabetic animals were in a chronic stress condition; (b) the threshold for steroid feedback was less sensitive to variations in plasma corticosterone; (c) there is an abnormal peripheral disposal of corticosterone, but that other factors, besides the liver, regulate the clearance of the hormone from the circulation in the diabetic animals.", "contents": "Abnormal regulation of adrenal function in rats with streptozotocin diabetes. The factors that control adrenal steroid secretion and metabolism were investigated in rats made diabetic with Streptozotocin (65 mg/kg) and used one month after treatment. Diabetic animals possessed high resting levels of plasma corticosterone accompanied by adrenal hypertrophy; the showed an increased response to the stress of i.p. cold water injection. Moreover, the pituitaries of diabetic rats seemed to be releasing ACTH continuously and not storing it. Upon adrenal inhibition with Aminoglutethimide the expected increase in adrenal cholesterol and weight was of a smaller magnitude than in controls. The activity of liver enzymes that reduce ring A of corticosterone showed decreased activity in diabetics, which suggests that more corticosterone rather than its inactive metabolites were available to--but not able to suppress--the steroid feedback sites. The half-life of corticosterone in blood was similar in diabetes and controls. These results suggest that (a) diabetic animals were in a chronic stress condition; (b) the threshold for steroid feedback was less sensitive to variations in plasma corticosterone; (c) there is an abnormal peripheral disposal of corticosterone, but that other factors, besides the liver, regulate the clearance of the hormone from the circulation in the diabetic animals."}
{"id": "PMID:201546", "title": "Studies on the occurrence and distribution of HI antibodies against some arboviruses in the serum of domestic mammals in Puglia.", "content": "The virological and serological studies previously carried out on arboviruses in Italy are reviewed. The presence of antibodies to 11 arboviruses was investigated in the serum of various domestic animals (100 horses, 107 pigs, 102 sheep, 205 goats, 100 cattle and 200 dogs) from some areas of Puglia. The techniques are described. The results, given in tables and discussed in detail, support the hypothesis that in this region also there are arboviruses circulating, particularly those of group B.", "contents": "Studies on the occurrence and distribution of HI antibodies against some arboviruses in the serum of domestic mammals in Puglia. The virological and serological studies previously carried out on arboviruses in Italy are reviewed. The presence of antibodies to 11 arboviruses was investigated in the serum of various domestic animals (100 horses, 107 pigs, 102 sheep, 205 goats, 100 cattle and 200 dogs) from some areas of Puglia. The techniques are described. The results, given in tables and discussed in detail, support the hypothesis that in this region also there are arboviruses circulating, particularly those of group B."}
{"id": "PMID:201551", "title": "Triiodothyronine receptors in lymphocytes of newborn and adult rats.", "content": "Cytoplasmic and nuclear incorporation of 125I triiodothyronine by thymic lymphocytes has been demonstrated by electron microscopic autoradiography. Incorporation was significantly more pronounced in the newborn than in the adult age. The information emerging from the experime,tal observations contributes further evidence to the more precise interpretation of receptor maturation.", "contents": "Triiodothyronine receptors in lymphocytes of newborn and adult rats. Cytoplasmic and nuclear incorporation of 125I triiodothyronine by thymic lymphocytes has been demonstrated by electron microscopic autoradiography. Incorporation was significantly more pronounced in the newborn than in the adult age. The information emerging from the experime,tal observations contributes further evidence to the more precise interpretation of receptor maturation."}
{"id": "PMID:201547", "title": "Presence of Aujeszky's disease virus in organs and materials from experimentally infected dogs.", "content": "The presence of Aujeszky's disease virus was investigated in various organs and materials from experimentally infected dogs, employing the fluorescent antibody test (FAT), tissue culture and biological tests in rabbits. The FAT appeared less sensitive for virus detection than virus isolation in cell culture and rabbit tests. The virus distribution in the central nervous system was related to the site of inoculation.", "contents": "Presence of Aujeszky's disease virus in organs and materials from experimentally infected dogs. The presence of Aujeszky's disease virus was investigated in various organs and materials from experimentally infected dogs, employing the fluorescent antibody test (FAT), tissue culture and biological tests in rabbits. The FAT appeared less sensitive for virus detection than virus isolation in cell culture and rabbit tests. The virus distribution in the central nervous system was related to the site of inoculation."}
{"id": "PMID:201552", "title": "Hyperinsulinemic hypoglycemia: effect of epinephrine suppression.", "content": "The inhibitory effect of epinephrine on basal and tolbutamide-stimulated insulin release was studied in 5 patients with hyperinsulinemic hypoglycemia. Epinephrine inhibited both basal and tolbutamide-induced insulin release in patients with beta-cell adenoma and hyperplasia, but failed to inhibit insulin release in a patient with beta-cell carcinoma. The inhibition of basal insulin with epinephrine was maximum in patients with beta-cell hyperplasia. This differential inhibitory effect of epinephrine on insulin release may prove to be a useful screening test in the preoperative diagnosis of the nature of the lesion producing hyperinsulinemia.", "contents": "Hyperinsulinemic hypoglycemia: effect of epinephrine suppression. The inhibitory effect of epinephrine on basal and tolbutamide-stimulated insulin release was studied in 5 patients with hyperinsulinemic hypoglycemia. Epinephrine inhibited both basal and tolbutamide-induced insulin release in patients with beta-cell adenoma and hyperplasia, but failed to inhibit insulin release in a patient with beta-cell carcinoma. The inhibition of basal insulin with epinephrine was maximum in patients with beta-cell hyperplasia. This differential inhibitory effect of epinephrine on insulin release may prove to be a useful screening test in the preoperative diagnosis of the nature of the lesion producing hyperinsulinemia."}
{"id": "PMID:201554", "title": "Effect of hyperprolactinemia on pituitary-adrenal function.", "content": "Three patients with hyperprolactinemia (2 with pituitary tumors and 1 with a hypothalamic disturbance) underwent evaluation of their hypothalamic-pituitary-adrenal axis using ACTH, metyrapone and in one case repetitive insulin tolerance tests. With the exception of a suggestion of a slight increase in adrenal responsiveness to pharmacological doses of ACTH in one of the patients, there was no alteration in the adrenal responsiveness of the 3 patients evaluated. We conclude that hyperprolactinemia probably does not systematically modify the responsiveness of the hypothalamic-pituitary-adrenal axis.", "contents": "Effect of hyperprolactinemia on pituitary-adrenal function. Three patients with hyperprolactinemia (2 with pituitary tumors and 1 with a hypothalamic disturbance) underwent evaluation of their hypothalamic-pituitary-adrenal axis using ACTH, metyrapone and in one case repetitive insulin tolerance tests. With the exception of a suggestion of a slight increase in adrenal responsiveness to pharmacological doses of ACTH in one of the patients, there was no alteration in the adrenal responsiveness of the 3 patients evaluated. We conclude that hyperprolactinemia probably does not systematically modify the responsiveness of the hypothalamic-pituitary-adrenal axis."}
{"id": "PMID:201560", "title": "Fetal mouse lung in circumfusion system cultures.", "content": "Fetal mouse lungs were cultivated, using the dual-rotary circumfusion system for tissue culture, and their histotypic development was surveyed for 75 days by phase-contrast and electron microscopy. Alveoli, terminal bronchioles and alveolar macrophages were photographed periodically with still and time-lapse phase-contrast microscopy. Their histotypic appearance was confirmed by electron micrographs of the 1- and 2 1/2-month-old specimens. These revealed typical alveoli surrounded by a basal lamina and composed of types I and II pneumocytes containing various lamellar-body forms within the type II cells, the alveolar lumen, and the alveolar macrophages. There was a shift from almost all type II cells in the 1-month-old alveoli to the presence of frequent type I cells as constituents of the alveoli in the 2 1/2-month-old cultures. The terminal bronchioles were tubules consisting of ciliated cells with Clara cells interspersed between them. The ciliated cells contained as many as 30 cilia or basal bodies per section and numerous microvilli. They were attached to each other and to the Clara cells by junctional complexes and accessory desmosomes which were generally in the apical ends of the cells. The Clara cells typically had glycogen granules interspersed between lamellae of the endoplasmic reticulum, contained numerous well dispersed mitochondria, occasional lysosome-like granules and crystalloid bodies which appeared to be tubular. Some Clara cells presented a moderatley dense secretory granule in the center of the whorl of the endoplasmic reticulum.", "contents": "Fetal mouse lung in circumfusion system cultures. Fetal mouse lungs were cultivated, using the dual-rotary circumfusion system for tissue culture, and their histotypic development was surveyed for 75 days by phase-contrast and electron microscopy. Alveoli, terminal bronchioles and alveolar macrophages were photographed periodically with still and time-lapse phase-contrast microscopy. Their histotypic appearance was confirmed by electron micrographs of the 1- and 2 1/2-month-old specimens. These revealed typical alveoli surrounded by a basal lamina and composed of types I and II pneumocytes containing various lamellar-body forms within the type II cells, the alveolar lumen, and the alveolar macrophages. There was a shift from almost all type II cells in the 1-month-old alveoli to the presence of frequent type I cells as constituents of the alveoli in the 2 1/2-month-old cultures. The terminal bronchioles were tubules consisting of ciliated cells with Clara cells interspersed between them. The ciliated cells contained as many as 30 cilia or basal bodies per section and numerous microvilli. They were attached to each other and to the Clara cells by junctional complexes and accessory desmosomes which were generally in the apical ends of the cells. The Clara cells typically had glycogen granules interspersed between lamellae of the endoplasmic reticulum, contained numerous well dispersed mitochondria, occasional lysosome-like granules and crystalloid bodies which appeared to be tubular. Some Clara cells presented a moderatley dense secretory granule in the center of the whorl of the endoplasmic reticulum."}
{"id": "PMID:201564", "title": "Enhancement of antibody-dependent cell-mediated cytotoxicity of herpesvirus-infected cells by complement.", "content": "An investigation was made of the effects of complement on the levels of antibody-dependence cytotoxicity (ADCC) mediated by bovine leukocytes against herpesvirus-infected target cells. Neutrophil-mediated ADCC was considerably enhanced upon the addition of low levels of complement that alone failed to induce lysis of antibody-sensitized target cells. This enhancement was most apparent under suboptimum conditions such as at low effector-to-target cell ratios, low levels of sensitizing antiserum, and short-duration assays. Furthermore, cells and classes of immunoglobulin unable to induce ADCC could do so in the presence of complement. The action of complement is considered in terms of a more tenacious bond formed between effector and target cells. The implications of the results are discussed in terms of the part that complement might play in enhancing antiviral recovery processes.", "contents": "Enhancement of antibody-dependent cell-mediated cytotoxicity of herpesvirus-infected cells by complement. An investigation was made of the effects of complement on the levels of antibody-dependence cytotoxicity (ADCC) mediated by bovine leukocytes against herpesvirus-infected target cells. Neutrophil-mediated ADCC was considerably enhanced upon the addition of low levels of complement that alone failed to induce lysis of antibody-sensitized target cells. This enhancement was most apparent under suboptimum conditions such as at low effector-to-target cell ratios, low levels of sensitizing antiserum, and short-duration assays. Furthermore, cells and classes of immunoglobulin unable to induce ADCC could do so in the presence of complement. The action of complement is considered in terms of a more tenacious bond formed between effector and target cells. The implications of the results are discussed in terms of the part that complement might play in enhancing antiviral recovery processes."}
{"id": "PMID:201565", "title": "Purification of beta-toxin from Clostridium perfringens type C.", "content": "Beta-toxin was purified about 340-fold from culture supernatant fluid of Clostridium perfringens type C with a yield of about 24% in terms of biologically active beta-toxin. The purification involved ammonium sulfate fractionation, gel filtration through Sephadex G-100, isoelectrofocusing in a pH 3 to 6 gradient, and immunoaffinity chromatography. The purified beta-toxin gave a single band on polyacrylamide gel electrophoresis.", "contents": "Purification of beta-toxin from Clostridium perfringens type C. Beta-toxin was purified about 340-fold from culture supernatant fluid of Clostridium perfringens type C with a yield of about 24% in terms of biologically active beta-toxin. The purification involved ammonium sulfate fractionation, gel filtration through Sephadex G-100, isoelectrofocusing in a pH 3 to 6 gradient, and immunoaffinity chromatography. The purified beta-toxin gave a single band on polyacrylamide gel electrophoresis."}
{"id": "PMID:201566", "title": "Alteration of host defense mechanisms by murine cytomegalovirus infection.", "content": "An animal model of a sublethal infection, utilizing murine cytomegalovirus (MCMV), was developed to determine whether immunological factors could contribute to the establishment of a persistent viral infection. Adult female C3H mice inoculated intraperitoneally with 10(5) plaque-forming units of MCMV developed splenomegaly 5 to 12 days after infection. Virus replicated to peak titers (10(3) to 10(6) plaque-forming units per g of tissue) in liver, spleen, lung, kidney, and salivary gland tissue during the acute phase of the infection (3 to 12 days); it then decreased to undetectable levels in all tissues except salivary gland. Serum interferon was detected as early as 12 h after infection, peaked at 36 h (1,093 U/ml), and was undetectable by 4 days after infection. MCMV-infected animals were hyporeactive to interferon induction with New castle disease virus on days 5 to 9 of the infection. Splenic lymphocyte reactivity to phytohemagglutinin and lipopolysaccharide was normal early during the course of the infection, was suppressed during the acute phase of the infection, and had returned to normal by day 18. These data indicate that several parameters of host defense are transiently suppressed during the course of a MCMV infection. The capacity of cytomegaloviruses to alter host resistance may be one factor that contributes to the establishment of a persistent infection.", "contents": "Alteration of host defense mechanisms by murine cytomegalovirus infection. An animal model of a sublethal infection, utilizing murine cytomegalovirus (MCMV), was developed to determine whether immunological factors could contribute to the establishment of a persistent viral infection. Adult female C3H mice inoculated intraperitoneally with 10(5) plaque-forming units of MCMV developed splenomegaly 5 to 12 days after infection. Virus replicated to peak titers (10(3) to 10(6) plaque-forming units per g of tissue) in liver, spleen, lung, kidney, and salivary gland tissue during the acute phase of the infection (3 to 12 days); it then decreased to undetectable levels in all tissues except salivary gland. Serum interferon was detected as early as 12 h after infection, peaked at 36 h (1,093 U/ml), and was undetectable by 4 days after infection. MCMV-infected animals were hyporeactive to interferon induction with New castle disease virus on days 5 to 9 of the infection. Splenic lymphocyte reactivity to phytohemagglutinin and lipopolysaccharide was normal early during the course of the infection, was suppressed during the acute phase of the infection, and had returned to normal by day 18. These data indicate that several parameters of host defense are transiently suppressed during the course of a MCMV infection. The capacity of cytomegaloviruses to alter host resistance may be one factor that contributes to the establishment of a persistent infection."}
{"id": "PMID:201567", "title": "Replication of parainfluenza type 3 virus in alveolar macrophages: evidence of in vivo infection and of in vitro temperature sensitivity in virus maturation.", "content": "Approximately 2% of cultured alveolar macrophages (AM), originally lavaged from the lungs of parainfluenza type 3 virus (PI-3V)-infected calves, were observed to contain viral antigen (by fluorescent antibody method) or viral nucleocapsids (by electron microscopy). Plaque assays, however, indicated that virus titers were generally low when cultures were incubated at 37 degrees C for 10 days. AM, obtained from \"in vivo infected\" and \"noninfected\" calves, were found to be equally susceptible to further in vitro PI-3V infection when cultures were incubated at 37 degrees C. AM that were obtained from the lungs of normal calves, cultured at 37 degrees C, and inoculated with PI-3V were observed to produce relatively high virus titers when the incubation temperature was shifted down to 32 degrees C. Results from hemagglutinin assays showed that considerable amounts of hemagglutinin were detected when AM cultures were incubated at 32 degrees C, but only limited amounts were detected at 37 degrees C. Results from electron microscopic examinations at both temperatures substantiated the results of plaque and hemagglutinin assays. The PI-3V, isolated from AM cultures incubated at 32 degrees C, grew well in Madin-Darby bovine kidney cells at 32 degrees C, but little virus was produced at 37 degrees C. In contrast, parent PI-3V grew equally well at both temperatures. The results are discussed in terms of host susceptibility, temperature-sensitivity and virus maturation, and surface viral antigens and persistent viral infection.", "contents": "Replication of parainfluenza type 3 virus in alveolar macrophages: evidence of in vivo infection and of in vitro temperature sensitivity in virus maturation. Approximately 2% of cultured alveolar macrophages (AM), originally lavaged from the lungs of parainfluenza type 3 virus (PI-3V)-infected calves, were observed to contain viral antigen (by fluorescent antibody method) or viral nucleocapsids (by electron microscopy). Plaque assays, however, indicated that virus titers were generally low when cultures were incubated at 37 degrees C for 10 days. AM, obtained from \"in vivo infected\" and \"noninfected\" calves, were found to be equally susceptible to further in vitro PI-3V infection when cultures were incubated at 37 degrees C. AM that were obtained from the lungs of normal calves, cultured at 37 degrees C, and inoculated with PI-3V were observed to produce relatively high virus titers when the incubation temperature was shifted down to 32 degrees C. Results from hemagglutinin assays showed that considerable amounts of hemagglutinin were detected when AM cultures were incubated at 32 degrees C, but only limited amounts were detected at 37 degrees C. Results from electron microscopic examinations at both temperatures substantiated the results of plaque and hemagglutinin assays. The PI-3V, isolated from AM cultures incubated at 32 degrees C, grew well in Madin-Darby bovine kidney cells at 32 degrees C, but little virus was produced at 37 degrees C. In contrast, parent PI-3V grew equally well at both temperatures. The results are discussed in terms of host susceptibility, temperature-sensitivity and virus maturation, and surface viral antigens and persistent viral infection."}
{"id": "PMID:201568", "title": "Respiratory infection in mice with sialodacryoadenitis virus, a coronavirus of rats.", "content": "Sialodacryoadenitis virus (SDAV), a coronavirus of rats, evoked both serum neutralization and complement fixation antibody responses when inoculated intranasally in mice. Weanling gnotobiotic CD-1 mice inoculated intranasally with 10(3.0) mean tissue culture infective doses of SDAV remained asymptomatic. Virus was recovered from the nasopharynx, trachea, and lung from day 2 to day 7. Viral antigen was readily detected by indirect immunofluorescence in the lung but rarely in the nasopharynx. Infected mice developed interstitial pneumonia. Susceptible mice contact exposed to experimentally infected mice developed antibody to SDAV. Epizootiological studies indicated that retired breeder mice can have complement-fixing antibody to SDAV and mouse hepatitis virus (MHV) in the absence of MHV infection. These studies show that SDAV is infectious for mice and can be a pathogen for the respiratory system. Thus, SDAV infection of mice may be responsible for spurious seroconversions to MHV.", "contents": "Respiratory infection in mice with sialodacryoadenitis virus, a coronavirus of rats. Sialodacryoadenitis virus (SDAV), a coronavirus of rats, evoked both serum neutralization and complement fixation antibody responses when inoculated intranasally in mice. Weanling gnotobiotic CD-1 mice inoculated intranasally with 10(3.0) mean tissue culture infective doses of SDAV remained asymptomatic. Virus was recovered from the nasopharynx, trachea, and lung from day 2 to day 7. Viral antigen was readily detected by indirect immunofluorescence in the lung but rarely in the nasopharynx. Infected mice developed interstitial pneumonia. Susceptible mice contact exposed to experimentally infected mice developed antibody to SDAV. Epizootiological studies indicated that retired breeder mice can have complement-fixing antibody to SDAV and mouse hepatitis virus (MHV) in the absence of MHV infection. These studies show that SDAV is infectious for mice and can be a pathogen for the respiratory system. Thus, SDAV infection of mice may be responsible for spurious seroconversions to MHV."}
{"id": "PMID:201569", "title": "Interferon induction by vesicular stomatitis virus and its role in virus replication.", "content": "Antibody against human fibroblast interferon increased the yields of vesicular stomatitis virus in human cells. The results show that endogenous interferon produced in the course of multicycle vesicular stomatitis virus infection depresses virus yields.", "contents": "Interferon induction by vesicular stomatitis virus and its role in virus replication. Antibody against human fibroblast interferon increased the yields of vesicular stomatitis virus in human cells. The results show that endogenous interferon produced in the course of multicycle vesicular stomatitis virus infection depresses virus yields."}
{"id": "PMID:201570", "title": "Effect of input multiplicity on the establishment of simian virus 40 persistent infections in rhesus monkey kidney cells.", "content": "Monolayer cultures of LLC-MK2 rhesus monkey kidney cells become persistently infected with simian virus 40 after infection at input multiplicities of 100, 10, or 1 plaque-forming unit per cell. After 3 weeks, all cells of the cultures infected at a multiplicity of 1 plaque-forming unit per cell produced the simian virus 40 T antigen. In contrast, 8 to 11 weeks elapsed before all the cells in the cultures infected at a multiplicity of 100 plaque-forming units per cell produced T antigen. Defective interfering particles and interferon production were not evident during this time.", "contents": "Effect of input multiplicity on the establishment of simian virus 40 persistent infections in rhesus monkey kidney cells. Monolayer cultures of LLC-MK2 rhesus monkey kidney cells become persistently infected with simian virus 40 after infection at input multiplicities of 100, 10, or 1 plaque-forming unit per cell. After 3 weeks, all cells of the cultures infected at a multiplicity of 1 plaque-forming unit per cell produced the simian virus 40 T antigen. In contrast, 8 to 11 weeks elapsed before all the cells in the cultures infected at a multiplicity of 100 plaque-forming units per cell produced T antigen. Defective interfering particles and interferon production were not evident during this time."}
{"id": "PMID:201571", "title": "Characterization of the allergenic components of the house dust mite, Dermatophagoides farinae.", "content": "Characterization and purification of the allergenic components of the house dust mite, Dermatophagoides farinae, were investigated. It was found that the mite antigen was heat-stable, pronase-sensitive, and periodate-resistant, which suggested that the antigenic determinants of the mite antigen resided mainly in the protein component. Purification of the mite antigen was tried using Sephadex G-150, DEAE cellulose, and isoelectrofocusing columns. The most potent allergenic fraction was around 20,000-30,000 in molecular weight, although the allergenic activity spread in a wide molecular weight range. Prausnitz-K\u00fcstner type skin reactions were performed on rats using mouse homocytotropic antibodies for allergenic evaluation, and the clinical usefulness of this method is discussed.", "contents": "Characterization of the allergenic components of the house dust mite, Dermatophagoides farinae. Characterization and purification of the allergenic components of the house dust mite, Dermatophagoides farinae, were investigated. It was found that the mite antigen was heat-stable, pronase-sensitive, and periodate-resistant, which suggested that the antigenic determinants of the mite antigen resided mainly in the protein component. Purification of the mite antigen was tried using Sephadex G-150, DEAE cellulose, and isoelectrofocusing columns. The most potent allergenic fraction was around 20,000-30,000 in molecular weight, although the allergenic activity spread in a wide molecular weight range. Prausnitz-K\u00fcstner type skin reactions were performed on rats using mouse homocytotropic antibodies for allergenic evaluation, and the clinical usefulness of this method is discussed."}
{"id": "PMID:201572", "title": "Chromosome banding, isoenzyme studies and determination of Epstein-Barr virus DNA content on human Burkitt lymphoma/mouse hybrids.", "content": "Four independently fused hybrid clones derived from a cross between the mouse mammary carcinoma TA3Ha and the human Burkitt lymphoma line Daudi were tested for the EBV-determined nuclear antigen (EBNA), EBV-DNA and the presence of human chromosomes, in the course of serial propagation in vitro. EBNA and EBV-DNA were lost in parallel with the loss of human chromosomes. It seems that the persistence of EB-viral genetic information does not require the presence of a specific human chromosome(s) in this particular hybrid combination.", "contents": "Chromosome banding, isoenzyme studies and determination of Epstein-Barr virus DNA content on human Burkitt lymphoma/mouse hybrids. Four independently fused hybrid clones derived from a cross between the mouse mammary carcinoma TA3Ha and the human Burkitt lymphoma line Daudi were tested for the EBV-determined nuclear antigen (EBNA), EBV-DNA and the presence of human chromosomes, in the course of serial propagation in vitro. EBNA and EBV-DNA were lost in parallel with the loss of human chromosomes. It seems that the persistence of EB-viral genetic information does not require the presence of a specific human chromosome(s) in this particular hybrid combination."}
{"id": "PMID:201573", "title": "Mechanism of the establishment of Epstein-Barr virus genome-containing lymphoid cell lines from infectious mononucleosis patients: studies with phosphonoacetate.", "content": "A concentration of disodium phosphonoacetate (PA) has been defined which will reduce the synthesis of infectious EB virus in a producer cell line to 1% of control values but which will not affect the growth of EB virus-transformed cells in a 12-week colony-forming assay. When total mononuclear cells or T-lymphocyte-depleted mononuclear cells from the blood of acute IM patients were cultured in the presence of PA at the above concentration, the regular establishment of EB virus genome-containing cell lines seen in control cultures was almost totally abolished. In further experiments, when T-lymphocyte-depleted IM mononuclear cells were co-cultivated with foetal cells of the opposite sex in the presence and absence of PA, cell lines of mixed or of exclusively foetal origin were obtained not only from control co-cultures but also on those rare occasions when transformed foci developed in PA-treated co-cultures. The results suggest that all cell lines derived from the blood of IM patients are initiated in culture by a two-step process of virus release and secondary infection, and argue against the occurrence of any direct outgrowth of IM cells transformed by the virus in vivo.", "contents": "Mechanism of the establishment of Epstein-Barr virus genome-containing lymphoid cell lines from infectious mononucleosis patients: studies with phosphonoacetate. A concentration of disodium phosphonoacetate (PA) has been defined which will reduce the synthesis of infectious EB virus in a producer cell line to 1% of control values but which will not affect the growth of EB virus-transformed cells in a 12-week colony-forming assay. When total mononuclear cells or T-lymphocyte-depleted mononuclear cells from the blood of acute IM patients were cultured in the presence of PA at the above concentration, the regular establishment of EB virus genome-containing cell lines seen in control cultures was almost totally abolished. In further experiments, when T-lymphocyte-depleted IM mononuclear cells were co-cultivated with foetal cells of the opposite sex in the presence and absence of PA, cell lines of mixed or of exclusively foetal origin were obtained not only from control co-cultures but also on those rare occasions when transformed foci developed in PA-treated co-cultures. The results suggest that all cell lines derived from the blood of IM patients are initiated in culture by a two-step process of virus release and secondary infection, and argue against the occurrence of any direct outgrowth of IM cells transformed by the virus in vivo."}
{"id": "PMID:201574", "title": "EBV specific secretory IgA in saliva of NPC patients. Presence of secretory piece in epithelial malignant cells.", "content": "Saliva samples from 59 patients with nasopharyngeal carcinoma (NPC) and from 20 normal individuals were studied to determine the nature and origin of the EBV-specific IgA in NPC saliva. About 50% of NPC saliva samples contained secretory IgA specific for EBV. The corresponding tumor IgA(alpha) was found in plasma cells surrounding the epithelial tumor cells and the secretory piece at the surface of epithelial cells. A slightly higher proportion of NPC saliva samples containing IgA was found in patients from Tunis than in samples from Hong Kong. Attention is drawn to the clinical value of the salivary IgA in diagnosis and monitoring of treatment of NPC.", "contents": "EBV specific secretory IgA in saliva of NPC patients. Presence of secretory piece in epithelial malignant cells. Saliva samples from 59 patients with nasopharyngeal carcinoma (NPC) and from 20 normal individuals were studied to determine the nature and origin of the EBV-specific IgA in NPC saliva. About 50% of NPC saliva samples contained secretory IgA specific for EBV. The corresponding tumor IgA(alpha) was found in plasma cells surrounding the epithelial tumor cells and the secretory piece at the surface of epithelial cells. A slightly higher proportion of NPC saliva samples containing IgA was found in patients from Tunis than in samples from Hong Kong. Attention is drawn to the clinical value of the salivary IgA in diagnosis and monitoring of treatment of NPC."}
{"id": "PMID:201576", "title": "An analysis of the accessibility and nonaccessibility of patients in a follow-up study.", "content": "In a follow-up study of 184 emergency room patients experiencing acute drug reactions, several respondents were inaccessible. In this paper the 83 accessible and 101 nonaccessible patients are compared in order to determine why respondents are often difficult to locate in a follow-up study. Those patients who were the most accessible proved to be primarily young, White males who had been referred to a traditional drug treatment program from the hospital emergency room. Those patients who were the least accessible proved to be primarily White females between 24 and 29 years of age who had not been referred for further treatment.", "contents": "An analysis of the accessibility and nonaccessibility of patients in a follow-up study. In a follow-up study of 184 emergency room patients experiencing acute drug reactions, several respondents were inaccessible. In this paper the 83 accessible and 101 nonaccessible patients are compared in order to determine why respondents are often difficult to locate in a follow-up study. Those patients who were the most accessible proved to be primarily young, White males who had been referred to a traditional drug treatment program from the hospital emergency room. Those patients who were the least accessible proved to be primarily White females between 24 and 29 years of age who had not been referred for further treatment."}
{"id": "PMID:201577", "title": "Methadone maintenance and narcotic blocking drugs.", "content": "Drugs which specifically antagonize certain of the actions of opioids are reviewed. These antagonists include nalorphine, levallorphan, naloxone, naltrexone, and cyclazocine. Programs involving antagonist treatment are discussed.", "contents": "Methadone maintenance and narcotic blocking drugs. Drugs which specifically antagonize certain of the actions of opioids are reviewed. These antagonists include nalorphine, levallorphan, naloxone, naltrexone, and cyclazocine. Programs involving antagonist treatment are discussed."}
{"id": "PMID:201578", "title": "Plotting regression lines for a new beta-lactam antibiotic (mecillinam).", "content": "Regression lines for mecillinam (FL 1060) were established according to the recommendations of th ICS. The investigation involved 477 Gram-negative and Gram-positive organisms with the widest possible spectrum of sensitivity which were isolated from fresh material for examination. Solid and liquid M\u00fcller-Hinton media (Merck and BBL) were used as nutrient media. The Difco M\u00fcller-Hinton medium is not suitable for this subtance because of the high ionic content. A general regression line for mecillinam is not admissible. The considerably restricted sphere of indication shown by our studies is presented with reference to the blood levels attainable in vivo. At the same time, the good sensivity of salmonella is pointed out.", "contents": "Plotting regression lines for a new beta-lactam antibiotic (mecillinam). Regression lines for mecillinam (FL 1060) were established according to the recommendations of th ICS. The investigation involved 477 Gram-negative and Gram-positive organisms with the widest possible spectrum of sensitivity which were isolated from fresh material for examination. Solid and liquid M\u00fcller-Hinton media (Merck and BBL) were used as nutrient media. The Difco M\u00fcller-Hinton medium is not suitable for this subtance because of the high ionic content. A general regression line for mecillinam is not admissible. The considerably restricted sphere of indication shown by our studies is presented with reference to the blood levels attainable in vivo. At the same time, the good sensivity of salmonella is pointed out."}
{"id": "PMID:201579", "title": "Hyperdynamic beta-adrenergic circulatory state. A case report.", "content": "A 22-year-old Japanese male with hyperdynamic beta-adrenergic circulatr without premedication. An abnormal electrocardiographic pattern was observed during the dental treatment, which was analyzed from the standpoint of beta-adrenergic receptors and drugs. During treatment, local anesthetics without adrenergic beta-stimulant would be desirable but premedication with beta blocker may be enough even when anesthetic agents with beta-stimulators are used. Furthermore, premedication with minor tranquilizers is also effective.", "contents": "Hyperdynamic beta-adrenergic circulatory state. A case report. A 22-year-old Japanese male with hyperdynamic beta-adrenergic circulatr without premedication. An abnormal electrocardiographic pattern was observed during the dental treatment, which was analyzed from the standpoint of beta-adrenergic receptors and drugs. During treatment, local anesthetics without adrenergic beta-stimulant would be desirable but premedication with beta blocker may be enough even when anesthetic agents with beta-stimulators are used. Furthermore, premedication with minor tranquilizers is also effective."}
{"id": "PMID:201580", "title": "E.s.r. of spin-trapped radicals in aqueous solutions of amino acids. Reactions of the hydrated electron.", "content": "The reactions of hydrated electrons (eaq-) with amino acids were investigated by the spin-trapping method and by electron spin resonance. Tertiary nitrosobutane was used as a spin-trap to stabilize the short-lived radicals. Hydrated electrons were produced by gamma-radiolysis of de-aerated aqueous solutions of amino acids in the presence of sodium formate or tertiary butanol to scavenge OH. Radicals produced by reductive deamination of 19 amino acids were identified. Radicals formed by scission of the CH3-S- and -S-CH2- bonds of methionine as well as by deamination were observed. In the case of phenylalanine the radical formed by electron addition followed by proton transfer was identified. The reaction of proline and of hydroxyproline with eaq- resulted in the opening of the cyclic structure.", "contents": "E.s.r. of spin-trapped radicals in aqueous solutions of amino acids. Reactions of the hydrated electron. The reactions of hydrated electrons (eaq-) with amino acids were investigated by the spin-trapping method and by electron spin resonance. Tertiary nitrosobutane was used as a spin-trap to stabilize the short-lived radicals. Hydrated electrons were produced by gamma-radiolysis of de-aerated aqueous solutions of amino acids in the presence of sodium formate or tertiary butanol to scavenge OH. Radicals produced by reductive deamination of 19 amino acids were identified. Radicals formed by scission of the CH3-S- and -S-CH2- bonds of methionine as well as by deamination were observed. In the case of phenylalanine the radical formed by electron addition followed by proton transfer was identified. The reaction of proline and of hydroxyproline with eaq- resulted in the opening of the cyclic structure."}
{"id": "PMID:201581", "title": "Thiamine pyrophosphokinase activity in liver, heart and brain crude extracts of control and thiamine deficient rats.", "content": "The activity of thiamine pyrophosphokinase has been measured in liver, heart muscle and brain of normal and thiamine deficient rats. The activity measurement has been performed by use of thiamine-35S as substrate and separation of the reaction products by high voltage electrophoresis. KM has been determined as 7.1.10(-6) mol/l. The activity of thiamine pyrophosphokinase is reduced in liver and heart muscle of thiamine deficient rats significantly, whereas no decrease of the enzyme activity has been found in the brain. The content of thiamine pyrophosphate has been measured in the liver of normal and thiamine deficient rats. Injection of thiamine to deficient rats normalized the content of thiamine pyrophosphate in the liver within 6 hours. Our data suggest that thiamine pyrophosphokinase is an adaptive enzyme, the activity of which depends on the thiamine content of the cells.", "contents": "Thiamine pyrophosphokinase activity in liver, heart and brain crude extracts of control and thiamine deficient rats. The activity of thiamine pyrophosphokinase has been measured in liver, heart muscle and brain of normal and thiamine deficient rats. The activity measurement has been performed by use of thiamine-35S as substrate and separation of the reaction products by high voltage electrophoresis. KM has been determined as 7.1.10(-6) mol/l. The activity of thiamine pyrophosphokinase is reduced in liver and heart muscle of thiamine deficient rats significantly, whereas no decrease of the enzyme activity has been found in the brain. The content of thiamine pyrophosphate has been measured in the liver of normal and thiamine deficient rats. Injection of thiamine to deficient rats normalized the content of thiamine pyrophosphate in the liver within 6 hours. Our data suggest that thiamine pyrophosphokinase is an adaptive enzyme, the activity of which depends on the thiamine content of the cells."}
{"id": "PMID:201583", "title": "Photochemical inhibition of poliovirus replication by 4,5',8-trimethylpsoralen plus light.", "content": "Poliovirus replication in HeLa cells is significantly inhibited by a 30-min pulse of infected cells with 4,5',8-trimethylpsoralen plus long wavelength ultraviolet light. When infected cells are exposed to psoralen plus light during peak viral RNA synthesis, formation of virus-specific RNAs is inhibited. Viral RNA species, formed in vivo in the presence of, or treated in vitro with, psoralen plus light, appear to have become degraded when analyzed by sedimentation in sucrose-dimethyl sulfoxide gradients. Treatment with psoralen plus light in vitro results in the loss of infectivity of single-stranded viral RNA.", "contents": "Photochemical inhibition of poliovirus replication by 4,5',8-trimethylpsoralen plus light. Poliovirus replication in HeLa cells is significantly inhibited by a 30-min pulse of infected cells with 4,5',8-trimethylpsoralen plus long wavelength ultraviolet light. When infected cells are exposed to psoralen plus light during peak viral RNA synthesis, formation of virus-specific RNAs is inhibited. Viral RNA species, formed in vivo in the presence of, or treated in vitro with, psoralen plus light, appear to have become degraded when analyzed by sedimentation in sucrose-dimethyl sulfoxide gradients. Treatment with psoralen plus light in vitro results in the loss of infectivity of single-stranded viral RNA."}
{"id": "PMID:201585", "title": "Hemagglutination and hemagglutination-inhibition studies with a strain of Nebraska calf diarrhea virus (bovine rotavirus).", "content": "A hemagglutinin has been prepared from Nebraska calf diarrhea virus (NCDV) propagated in BS-C-1 cell line. After cesium chloride centrifugation, the hemagglutinin of the bovine rotavirus was found to be associated with intact virions (density 1.355 g/ml) but not with virions lacking an outer capsid layer (density 1.375 g/ml). In hemagglutination-inhibition (HAI) tests, the hemagglutinin reacted specifically with NCDV serum, and HAI seroconversions were detected in some sera tested. Cross-reactions were observed in complement fixation tests between the human and bovine rotaviruses but were not demonstrated by HAI, suggesting that the hemagglutinin detects a specific rather than a group antibody response.", "contents": "Hemagglutination and hemagglutination-inhibition studies with a strain of Nebraska calf diarrhea virus (bovine rotavirus). A hemagglutinin has been prepared from Nebraska calf diarrhea virus (NCDV) propagated in BS-C-1 cell line. After cesium chloride centrifugation, the hemagglutinin of the bovine rotavirus was found to be associated with intact virions (density 1.355 g/ml) but not with virions lacking an outer capsid layer (density 1.375 g/ml). In hemagglutination-inhibition (HAI) tests, the hemagglutinin reacted specifically with NCDV serum, and HAI seroconversions were detected in some sera tested. Cross-reactions were observed in complement fixation tests between the human and bovine rotaviruses but were not demonstrated by HAI, suggesting that the hemagglutinin detects a specific rather than a group antibody response."}
{"id": "PMID:201586", "title": "Detection of herpes simplex virus thymidine kinase polypeptides in cells labeled with 35S-methionine.", "content": "To investigate the size of herpes simplex virus (HSV) thymidine kinase (TK) polypeptides, procedures have been devised to purify the enzyme from infected cells labeled with 35S-methionine by (i) affinity chromatography on Sepharose-5'-amino-5'-deoxythymidine; (ii) preparative isoelectric focusing or preparative PAGE; and (iii) glycerol gradient centrifugation. Portions of enzyme fractions, at each purification step, were also treated with an immunoadsorbent, Sepharose-anti-HSV-1 TK immunoglobulin (IgG). Labeled polypeptides eluted from the immunoadsorbent were analyzed by electrophoresis in SDS slab gels and autoradiography. The results demonstrate that the molecular weights of HSV TK polypeptides are about 40,000. TK-negative HSV-1 mutant B2006 failed to induce the 40 K dalton polypeptide.", "contents": "Detection of herpes simplex virus thymidine kinase polypeptides in cells labeled with 35S-methionine. To investigate the size of herpes simplex virus (HSV) thymidine kinase (TK) polypeptides, procedures have been devised to purify the enzyme from infected cells labeled with 35S-methionine by (i) affinity chromatography on Sepharose-5'-amino-5'-deoxythymidine; (ii) preparative isoelectric focusing or preparative PAGE; and (iii) glycerol gradient centrifugation. Portions of enzyme fractions, at each purification step, were also treated with an immunoadsorbent, Sepharose-anti-HSV-1 TK immunoglobulin (IgG). Labeled polypeptides eluted from the immunoadsorbent were analyzed by electrophoresis in SDS slab gels and autoradiography. The results demonstrate that the molecular weights of HSV TK polypeptides are about 40,000. TK-negative HSV-1 mutant B2006 failed to induce the 40 K dalton polypeptide."}
{"id": "PMID:201587", "title": "Correlation between polyion effect on cell susceptibility to in vitro infection with murine C-type viruses and polyion effect on some membrane-related functions.", "content": "Polyions were tested for effects on some membrane-related functions. Both polycations investigated reduced the negative surface charge of assay cells and enhanced in vitro infectivity of murine C-type viruses, but had no influence on leukemia-virus-induced XC cell syncytia formation. Three polyanions increased the net outer cell charge, while only one of four inhibited infectivity and two of three impeded syncytia formation. Polyions had a slight, probably toxic, effect on the transmembrane potential, independent of their charge. Cells treated with fluorescent DEAE-dextran showed diffuse staining, which 4 h later had been modified into a granular fluorescence with unstained areas now present. This change correlated with a loss of enhancement of viral infectivity. The only polyanion which inhibited viral infectivity had a strong antihyaluronidase activity, and hyaluronidase and Ca++ both increased viral infectivity. It is suggested, therefore, that polyions may in part work on virus-cell membrane interactions by influencing membrane enzymes and not necessarily by simply changing the net outer cell surface charge.", "contents": "Correlation between polyion effect on cell susceptibility to in vitro infection with murine C-type viruses and polyion effect on some membrane-related functions. Polyions were tested for effects on some membrane-related functions. Both polycations investigated reduced the negative surface charge of assay cells and enhanced in vitro infectivity of murine C-type viruses, but had no influence on leukemia-virus-induced XC cell syncytia formation. Three polyanions increased the net outer cell charge, while only one of four inhibited infectivity and two of three impeded syncytia formation. Polyions had a slight, probably toxic, effect on the transmembrane potential, independent of their charge. Cells treated with fluorescent DEAE-dextran showed diffuse staining, which 4 h later had been modified into a granular fluorescence with unstained areas now present. This change correlated with a loss of enhancement of viral infectivity. The only polyanion which inhibited viral infectivity had a strong antihyaluronidase activity, and hyaluronidase and Ca++ both increased viral infectivity. It is suggested, therefore, that polyions may in part work on virus-cell membrane interactions by influencing membrane enzymes and not necessarily by simply changing the net outer cell surface charge."}
{"id": "PMID:201588", "title": "Characteristics of herpes simplex virus resistance to disodium phosphonoacetate.", "content": "Herpes simplex virus (HSV), which was partially resistant to the inhibitory effect of disodium phosphonoacetate (PAA), could be recovered following four virus passages in the presence of 100 microgram/ml PAA. Resistant strains were isolated from both HSV type 1 and HSV type 2. Virus resistance to PAA was not complete, and in most isolations a significant proportion of the virus stock remained susceptible to the drug. Resistance was shown to be heritable and persisted through virus passage and cloning experiments. PAA inhibited the replication of virus-specific DNA in sensitive strains of HSV but not in resistant strains of HSV. In vitro experiments directly demonstrated that PAA inhibited the activity of the virus-specific DNA polymerase 10 times more effectively in PAA-susceptible HSV than in PAA-resistant HSV. The treatment of HSV-infected mice with high levels of PAA did not induce the formation of resistant virus strains.", "contents": "Characteristics of herpes simplex virus resistance to disodium phosphonoacetate. Herpes simplex virus (HSV), which was partially resistant to the inhibitory effect of disodium phosphonoacetate (PAA), could be recovered following four virus passages in the presence of 100 microgram/ml PAA. Resistant strains were isolated from both HSV type 1 and HSV type 2. Virus resistance to PAA was not complete, and in most isolations a significant proportion of the virus stock remained susceptible to the drug. Resistance was shown to be heritable and persisted through virus passage and cloning experiments. PAA inhibited the replication of virus-specific DNA in sensitive strains of HSV but not in resistant strains of HSV. In vitro experiments directly demonstrated that PAA inhibited the activity of the virus-specific DNA polymerase 10 times more effectively in PAA-susceptible HSV than in PAA-resistant HSV. The treatment of HSV-infected mice with high levels of PAA did not induce the formation of resistant virus strains."}
{"id": "PMID:201589", "title": "Growth characteristics of acute hemorrhagic conjunctivitis virus in monkey kidney cells. III. Viral RNA synthesis at permissive and nonpermissive temperatures.", "content": "Monkey kidney cells infected with the J 670/71 strain of acute hemorrhagic conjunctivitis (AHC) virus in the presence of actinomycin D synthesized two species of viral RNA. One species had properties similar to the virion RNA, sedimented in a sucrose gradient with a sedimentation coefficient of 34S, and was sensitive to RNase. The other species sedimented at 18S and was resistant to RNase. The inability of AHC virus to replicate at 39 degrees was attributed to a lack of virus-specific RNA synthesis in infected cells.", "contents": "Growth characteristics of acute hemorrhagic conjunctivitis virus in monkey kidney cells. III. Viral RNA synthesis at permissive and nonpermissive temperatures. Monkey kidney cells infected with the J 670/71 strain of acute hemorrhagic conjunctivitis (AHC) virus in the presence of actinomycin D synthesized two species of viral RNA. One species had properties similar to the virion RNA, sedimented in a sucrose gradient with a sedimentation coefficient of 34S, and was sensitive to RNase. The other species sedimented at 18S and was resistant to RNase. The inability of AHC virus to replicate at 39 degrees was attributed to a lack of virus-specific RNA synthesis in infected cells."}
{"id": "PMID:201590", "title": "Application of the critical point dried whole cell technique to the study of animal rhabdoviruses.", "content": "The critical point dried (CPD) whole cell technique was applied to the study of the morphogenesis and morphology of rabies virus and vesicular stomatitis virus (VSV) in mouse neuroblastoma and baby hamster kidney (BHK) cells. With the stereoscopic technique, progeny viruses at the cell surface and within the cytoplasm of the CPD whole cells were clearly visualized. The presence of many fine cellular processes and of virus budding from these processes were prominent features of the infected cells. Long strings of virus particles and virus apparently fused into different forms were often seen; a possible mechanism for the formation of these aberrant forms is discussed. Negative staining of the CPD whole cells clearly revealed the detailed structure of virus particles in the process of budding.", "contents": "Application of the critical point dried whole cell technique to the study of animal rhabdoviruses. The critical point dried (CPD) whole cell technique was applied to the study of the morphogenesis and morphology of rabies virus and vesicular stomatitis virus (VSV) in mouse neuroblastoma and baby hamster kidney (BHK) cells. With the stereoscopic technique, progeny viruses at the cell surface and within the cytoplasm of the CPD whole cells were clearly visualized. The presence of many fine cellular processes and of virus budding from these processes were prominent features of the infected cells. Long strings of virus particles and virus apparently fused into different forms were often seen; a possible mechanism for the formation of these aberrant forms is discussed. Negative staining of the CPD whole cells clearly revealed the detailed structure of virus particles in the process of budding."}
{"id": "PMID:201591", "title": "Reiteration frequency of feline type C viral genomes in homologous and heterologous host cell DNA.", "content": "Differences in the multiplicity of proviral sequences of two feline endogenous viruses, RD-114 and FeLV, in homologous and heterologous host DNA were examined by viral cDNA hybridization using cellular DNA fractionated with respect to reiteration frequency. The endogenous proviral DNAs in cat cells were fractionated predominantly with intermediate-repeated sequences, while RD-114 proviral DNA in virus-infected human cells was fractionated together with unique-sequence DNA. These differences were consistent with the results of kinetic analysis using unfractionated DNA.", "contents": "Reiteration frequency of feline type C viral genomes in homologous and heterologous host cell DNA. Differences in the multiplicity of proviral sequences of two feline endogenous viruses, RD-114 and FeLV, in homologous and heterologous host DNA were examined by viral cDNA hybridization using cellular DNA fractionated with respect to reiteration frequency. The endogenous proviral DNAs in cat cells were fractionated predominantly with intermediate-repeated sequences, while RD-114 proviral DNA in virus-infected human cells was fractionated together with unique-sequence DNA. These differences were consistent with the results of kinetic analysis using unfractionated DNA."}
{"id": "PMID:201592", "title": "Serum angiotensin converting enzyme in sarcoidosis: clinical significance.", "content": "The elevated activity of serum angiotensin converting enzyme (ACE) in sarcoidosis was usually reduced during steroid therapy but remained above the normal value (52 nmol-min-1-ml-1) in approximately a third of patients during the first year of therapy. ACE was elevated in 5 of 10 patients treated with steroids for at least four years. It was significantly higher in untreated patients (placebo group), who were subsequently placed on steroid therapy because of clinical deterioration, than in those remaining on placebo therapy. In general ACE tended to diminish with increasing duration of disease. The results suggest that serial study of ACE may be useful in the clinical management of sarcoidosis, including assessment of the degree of activity, the need for steroid therapy, therapeutic result and the prognosis.", "contents": "Serum angiotensin converting enzyme in sarcoidosis: clinical significance. The elevated activity of serum angiotensin converting enzyme (ACE) in sarcoidosis was usually reduced during steroid therapy but remained above the normal value (52 nmol-min-1-ml-1) in approximately a third of patients during the first year of therapy. ACE was elevated in 5 of 10 patients treated with steroids for at least four years. It was significantly higher in untreated patients (placebo group), who were subsequently placed on steroid therapy because of clinical deterioration, than in those remaining on placebo therapy. In general ACE tended to diminish with increasing duration of disease. The results suggest that serial study of ACE may be useful in the clinical management of sarcoidosis, including assessment of the degree of activity, the need for steroid therapy, therapeutic result and the prognosis."}
{"id": "PMID:201593", "title": "Increased serum angiotensin converting enzyme activity in sarcoidosis.", "content": "The activity of serum angiotensin converting enzyme (ACE), assayed fluorometrically with the substrate hippuryl-L-histidyl-L-leucine was significantly higher in 116 patients with sarcoidosis than in 415 patients with other diseases--pulmonary and nonpulmonary--and in 58 normal subjects. Serum ACE was elevated in 59% of 46 recently diagnosed, untreated patients with sarcoidosis and was significantly reduced following steroid therapy in three patients with sarcoidosis, but in only one of four patients treated with placebos. The results suggest that elevated serum ACE activity is a valuable, although not absolutely specific, diagnostic indicator of sarcoidosis. It should be stressed that a normal value does not rule out the disease, and that steroid therapy tends to reduce the serum ACE activity.", "contents": "Increased serum angiotensin converting enzyme activity in sarcoidosis. The activity of serum angiotensin converting enzyme (ACE), assayed fluorometrically with the substrate hippuryl-L-histidyl-L-leucine was significantly higher in 116 patients with sarcoidosis than in 415 patients with other diseases--pulmonary and nonpulmonary--and in 58 normal subjects. Serum ACE was elevated in 59% of 46 recently diagnosed, untreated patients with sarcoidosis and was significantly reduced following steroid therapy in three patients with sarcoidosis, but in only one of four patients treated with placebos. The results suggest that elevated serum ACE activity is a valuable, although not absolutely specific, diagnostic indicator of sarcoidosis. It should be stressed that a normal value does not rule out the disease, and that steroid therapy tends to reduce the serum ACE activity."}
{"id": "PMID:201597", "title": "Infectious bovine rhinotracheitis: a review and update.", "content": "Infectious bovine rhinotracheitis (IBR), a herpesvirus infection of cattle, has diverse clinical manifestations. Known mainly as a respiratory tract disease characterized by tracheitis, rhinitis, and fever, IBR plays a prominent role among causes of undifferentiated bovine respiratory disease and abortion. It also causes conjunctivitis, infectious pustular vulvovaginitis, balanoposthitis, and rarely, encephalitis. The virus is readily transmitted and has worldwide distribution. Some cattle develop a latent infection, which can be reactivated. The disease can be diagnosed by clinical signs and lesions and by a variety of virologic and immunologic techniques. Control of IBR is based largely on vaccination. A review is timely because efficient utilization of the wide assortment of available vaccines requires knowledge of recent developments in the diagnosis, immunology, and epidemiology of the disease.", "contents": "Infectious bovine rhinotracheitis: a review and update. Infectious bovine rhinotracheitis (IBR), a herpesvirus infection of cattle, has diverse clinical manifestations. Known mainly as a respiratory tract disease characterized by tracheitis, rhinitis, and fever, IBR plays a prominent role among causes of undifferentiated bovine respiratory disease and abortion. It also causes conjunctivitis, infectious pustular vulvovaginitis, balanoposthitis, and rarely, encephalitis. The virus is readily transmitted and has worldwide distribution. Some cattle develop a latent infection, which can be reactivated. The disease can be diagnosed by clinical signs and lesions and by a variety of virologic and immunologic techniques. Control of IBR is based largely on vaccination. A review is timely because efficient utilization of the wide assortment of available vaccines requires knowledge of recent developments in the diagnosis, immunology, and epidemiology of the disease."}
{"id": "PMID:201599", "title": "beta-Lactamase and beta-lactam antibiotics resistance in acinetobacter anitratum (syn: A. calcoaceticus).", "content": "The cephalosporin beta-lactamase (cephalosporinase) produced by Acinetobacter was studied. The enzyme was partially purified by means of column chromatography and its properties were investigated. The enzyme was induced by benzylpenicillin, 6-aminopenicillanic acid and cephaloridine. Its molecular weight is 30,000 its optimal temperature 40C, and its optimal pH 7.25 similar to 7.50. Substrate specificity studies using various cephalosporins and penicillins, showed that the enzyme functioned as a cephalosporinase rather than penicillinase.", "contents": "beta-Lactamase and beta-lactam antibiotics resistance in acinetobacter anitratum (syn: A. calcoaceticus). The cephalosporin beta-lactamase (cephalosporinase) produced by Acinetobacter was studied. The enzyme was partially purified by means of column chromatography and its properties were investigated. The enzyme was induced by benzylpenicillin, 6-aminopenicillanic acid and cephaloridine. Its molecular weight is 30,000 its optimal temperature 40C, and its optimal pH 7.25 similar to 7.50. Substrate specificity studies using various cephalosporins and penicillins, showed that the enzyme functioned as a cephalosporinase rather than penicillinase."}
{"id": "PMID:201602", "title": "Adrenocortical function in aging exercise-trained rats.", "content": "Plasma corticosterone concentrations and in vitro adrenal secretion of corticosterone were determined in exercise-trained rats. Rats, 100, 200, and 300 days of age, were trained for a 10-wk period by treadmill running. Following the training program, rats were subjected to an acute bout of swimming. Acute swimming elevated plasma corticosterone concentrations in all age groups. At 170 days of age, the plasma corticosterone concentration following swimming was higher in exercise-trained rats than in controls. The opposite was true of acutely swum rats at 270 and 370 days of age. Acute swimming elevated the in vitro adrenal gland response to adrenocorticotropic hormone stimulation in control rats at all ages and in trained rats at 170 days of age. The in vivo relationship of epinephrine and the pituitary adrenal system is suggested as a mechanism which could have caused this response. The relationship of secretion rates to plasma corticosterone concentrations indicated that extra-adrenal mechanisms, such as decreased turnover, were also responsible for the elevated plasma corticosterone levels observed in response to acute swimming.", "contents": "Adrenocortical function in aging exercise-trained rats. Plasma corticosterone concentrations and in vitro adrenal secretion of corticosterone were determined in exercise-trained rats. Rats, 100, 200, and 300 days of age, were trained for a 10-wk period by treadmill running. Following the training program, rats were subjected to an acute bout of swimming. Acute swimming elevated plasma corticosterone concentrations in all age groups. At 170 days of age, the plasma corticosterone concentration following swimming was higher in exercise-trained rats than in controls. The opposite was true of acutely swum rats at 270 and 370 days of age. Acute swimming elevated the in vitro adrenal gland response to adrenocorticotropic hormone stimulation in control rats at all ages and in trained rats at 170 days of age. The in vivo relationship of epinephrine and the pituitary adrenal system is suggested as a mechanism which could have caused this response. The relationship of secretion rates to plasma corticosterone concentrations indicated that extra-adrenal mechanisms, such as decreased turnover, were also responsible for the elevated plasma corticosterone levels observed in response to acute swimming."}
{"id": "PMID:201604", "title": "Oxidation of cerebral cytochrome aa3 by oxygen plus carbon dioxide at hyperbaric pressures.", "content": "The reduction-oxidation level of cytochrome aa3 in the intact cerebral cortex of cerveau isol\u00e9 or pentobarbital-anesthetized cats was monitored by means of dual-beam reflectance spectrophotometry. Respiratory gases containing varying fractions of carbon dioxide and oxygen were administered at increased pressures, allowing titration of the cytochrome redox state from maximum reduction during nitrogen ventilation to the completely oxidized state. We show that the fully oxidized state could be reached with about 5% CO2-95% O2 inspired at 4 ATA. Maximum oxidation was achieved only through the relaxation of oxygen-induced vasoconstriction of the cerebral vessels, as our data indicated that large blood volume responses accompanied the increases in inspired carbon dioxide. With out technique, we have established that under resting air-breathing conditions cytochrome aa3 is about 85% reduced in the cat cerebral cortex, and that the absorption peak for cytochrome aa3 in situ is located near 602 nm. A free energy change of an additional 8 kcal is calculated to occur with donation of an electron pair from 85% reduced cytochrome aa3 to oxygen as compared to a 1% reduction level.", "contents": "Oxidation of cerebral cytochrome aa3 by oxygen plus carbon dioxide at hyperbaric pressures. The reduction-oxidation level of cytochrome aa3 in the intact cerebral cortex of cerveau isol\u00e9 or pentobarbital-anesthetized cats was monitored by means of dual-beam reflectance spectrophotometry. Respiratory gases containing varying fractions of carbon dioxide and oxygen were administered at increased pressures, allowing titration of the cytochrome redox state from maximum reduction during nitrogen ventilation to the completely oxidized state. We show that the fully oxidized state could be reached with about 5% CO2-95% O2 inspired at 4 ATA. Maximum oxidation was achieved only through the relaxation of oxygen-induced vasoconstriction of the cerebral vessels, as our data indicated that large blood volume responses accompanied the increases in inspired carbon dioxide. With out technique, we have established that under resting air-breathing conditions cytochrome aa3 is about 85% reduced in the cat cerebral cortex, and that the absorption peak for cytochrome aa3 in situ is located near 602 nm. A free energy change of an additional 8 kcal is calculated to occur with donation of an electron pair from 85% reduced cytochrome aa3 to oxygen as compared to a 1% reduction level."}
{"id": "PMID:201606", "title": "Transport of antibiotics and metabolite analogs by systems under cyclic AMP control: positive selection of Salmonella typhimurium cya and crp mutants.", "content": "Mutants in the cyclic AMP (cAMP) control system in Salmonella typhimurium (cya = adenyl cyclase, crp = cAMP receptor protein) were partially resistant to growth inhibition by 22 antibiotics (including fosfomycin, nalidixic acid, and streptomycin) and 29 inhibitory analogs of normal bacterial fuel/carbon sources. This resistance was used as the basis for an efficient positive selection of cya and crp mutants. We propose that these antibiotics and analogs enter the bacteria through transport systems normally used for transporting fuel/carbon sources and that this is accomplished because of a structural similarity between the antibiotic and the natural substrate of the particular transport system involved. We propose that these transport systems are all under positive control by cAMP and that cAMP acts as a signal molecule (alarmone) for fuel/carbon deprivation. Evidence is provided for a hierarchy within operons controlled by cAMP. The methodology is shown to be useful for analyzing both antibiotic transport systems and the cAMP super-control system.", "contents": "Transport of antibiotics and metabolite analogs by systems under cyclic AMP control: positive selection of Salmonella typhimurium cya and crp mutants. Mutants in the cyclic AMP (cAMP) control system in Salmonella typhimurium (cya = adenyl cyclase, crp = cAMP receptor protein) were partially resistant to growth inhibition by 22 antibiotics (including fosfomycin, nalidixic acid, and streptomycin) and 29 inhibitory analogs of normal bacterial fuel/carbon sources. This resistance was used as the basis for an efficient positive selection of cya and crp mutants. We propose that these antibiotics and analogs enter the bacteria through transport systems normally used for transporting fuel/carbon sources and that this is accomplished because of a structural similarity between the antibiotic and the natural substrate of the particular transport system involved. We propose that these transport systems are all under positive control by cAMP and that cAMP acts as a signal molecule (alarmone) for fuel/carbon deprivation. Evidence is provided for a hierarchy within operons controlled by cAMP. The methodology is shown to be useful for analyzing both antibiotic transport systems and the cAMP super-control system."}
{"id": "PMID:201607", "title": "Mapping of the mecillinam-resistant, round morphological mutants of Escherichia coli.", "content": "Genes responsible for round morphology in mecillinam-resistant, round morphological mutants of Escherichia coli have been mapped. Three mutants, called rodX, mapped at around 14 min, and two, called rodY, mapped at around 70 min by P1 transduction. These are either the same or very close to the loci reported, respectively, for the rodA (H. Matsuzawa, K. Hayakawa, T. Sato, and K. Imahori, J. Bacteriol. 115:436-442, 1973) and envB genes (B. Westling-H\u00e4ggstr\u00f6m and S. Normark, J. Bacteriol. 123:75-82, 1975). This suggests that mecillinam can be used very efficiently to select for found morphological mutants of rodA and envB after nitrosoguanidine treatment.", "contents": "Mapping of the mecillinam-resistant, round morphological mutants of Escherichia coli. Genes responsible for round morphology in mecillinam-resistant, round morphological mutants of Escherichia coli have been mapped. Three mutants, called rodX, mapped at around 14 min, and two, called rodY, mapped at around 70 min by P1 transduction. These are either the same or very close to the loci reported, respectively, for the rodA (H. Matsuzawa, K. Hayakawa, T. Sato, and K. Imahori, J. Bacteriol. 115:436-442, 1973) and envB genes (B. Westling-H\u00e4ggstr\u00f6m and S. Normark, J. Bacteriol. 123:75-82, 1975). This suggests that mecillinam can be used very efficiently to select for found morphological mutants of rodA and envB after nitrosoguanidine treatment."}
{"id": "PMID:201608", "title": "Mycoplasma phosphoenolpyruvate-dependent sugar phosphotransferase system: glucose-negative mutant and regulation of intracellular cyclic AMP.", "content": "Glucose-negative mutants of Mycoplasma capricolum were selected for growth on fructose in the presence of the toxic glucose analog alpha-methyl-D-glucopyranoside. The mutants are defective in the phosphoenolpyruvate:sugar phosphotransferase system for glucose. One mutant, pts-4, was studied in detail. It lacks the glucose-specific, membrane-bound enzyme II, IIGlc, as well as the general, low-molecular-weight, phosphocarrier protein, HPr. In place of the latter, however, it has a fructose-specific protein, HPrFru. Consistent with these changes, the mutant lost the ability to grow on glucosamine and maltose but retained its ability to grow on sucrose. In the glucose-negative mutant, glucose did not regulate the intracellular concentration of cyclic AMP. The intracellular concentration of cyclic AMP in M. capricolum is regulated by the presence of metabolizable sugars. In the wild-type, both glucose and fructose reduced the intracellular concentration of cyclic AMP; however, in the glucose-negative mutant, glucose no longer regulated the intracellular level of cyclic AMP.", "contents": "Mycoplasma phosphoenolpyruvate-dependent sugar phosphotransferase system: glucose-negative mutant and regulation of intracellular cyclic AMP. Glucose-negative mutants of Mycoplasma capricolum were selected for growth on fructose in the presence of the toxic glucose analog alpha-methyl-D-glucopyranoside. The mutants are defective in the phosphoenolpyruvate:sugar phosphotransferase system for glucose. One mutant, pts-4, was studied in detail. It lacks the glucose-specific, membrane-bound enzyme II, IIGlc, as well as the general, low-molecular-weight, phosphocarrier protein, HPr. In place of the latter, however, it has a fructose-specific protein, HPrFru. Consistent with these changes, the mutant lost the ability to grow on glucosamine and maltose but retained its ability to grow on sucrose. In the glucose-negative mutant, glucose did not regulate the intracellular concentration of cyclic AMP. The intracellular concentration of cyclic AMP in M. capricolum is regulated by the presence of metabolizable sugars. In the wild-type, both glucose and fructose reduced the intracellular concentration of cyclic AMP; however, in the glucose-negative mutant, glucose no longer regulated the intracellular level of cyclic AMP."}
{"id": "PMID:201609", "title": "Elevated cyclic AMP concentration in streptomycin-dependent Escherichia coli.", "content": "Streptomycin-dependent Escherichic coli B and K-12 cultures, which have relaxed catabolite repression when grown to glucose-salts medium, have an elevated concentration of cyclic AMP.", "contents": "Elevated cyclic AMP concentration in streptomycin-dependent Escherichia coli. Streptomycin-dependent Escherichic coli B and K-12 cultures, which have relaxed catabolite repression when grown to glucose-salts medium, have an elevated concentration of cyclic AMP."}
{"id": "PMID:201610", "title": "Hydrolytic action of phospholipases on bacterial membranes.", "content": "Substrate specificities of phospholipases C[EC 3.1.4.3] from Clostridium novyi, Clostridium perfringens, Bacillus cereus, and Pseudomonas aureofaciens were studied under the same conditions. Phospholipases C from Clostridium novyi and Bacillus cereus show wide substrate specificities while those of Clostridium perfringens and Pseudomonas aureofaciens show relatively narrow specificities. On the basis of these results, the hydrolytic actions of these phospholipases on membrane lipids of Escherichia coli, Bacillus cereus, and Clostridium novyi were examined under the same conditions. The enzymes of Clostridium novyi and Bacillus cereus attacked all the membranes and their lipid extracts, hydrolyzing phosphatidylethanolamine, phosphatidylglycerol, lyso-phosphatidylethanolamine, and o-aminoacylphosphatidylglycerol. Phospholipase C from Pseudomonas aureofaciens attacked these three membranes and their lipid extracts, hydrolyzing phosphatidylethanolamine. Phospholipase C from Clostridium perfringens hardly attacked the phospholipids of these bacterial membranes. However, phospholipase C from Clostridium perfringens hydrolyzed phosphatidylethanolamine in a mixture containing lipid extract from Escherichia coli membrane and purified phosphatidylcholine from egg yolk.", "contents": "Hydrolytic action of phospholipases on bacterial membranes. Substrate specificities of phospholipases C[EC 3.1.4.3] from Clostridium novyi, Clostridium perfringens, Bacillus cereus, and Pseudomonas aureofaciens were studied under the same conditions. Phospholipases C from Clostridium novyi and Bacillus cereus show wide substrate specificities while those of Clostridium perfringens and Pseudomonas aureofaciens show relatively narrow specificities. On the basis of these results, the hydrolytic actions of these phospholipases on membrane lipids of Escherichia coli, Bacillus cereus, and Clostridium novyi were examined under the same conditions. The enzymes of Clostridium novyi and Bacillus cereus attacked all the membranes and their lipid extracts, hydrolyzing phosphatidylethanolamine, phosphatidylglycerol, lyso-phosphatidylethanolamine, and o-aminoacylphosphatidylglycerol. Phospholipase C from Pseudomonas aureofaciens attacked these three membranes and their lipid extracts, hydrolyzing phosphatidylethanolamine. Phospholipase C from Clostridium perfringens hardly attacked the phospholipids of these bacterial membranes. However, phospholipase C from Clostridium perfringens hydrolyzed phosphatidylethanolamine in a mixture containing lipid extract from Escherichia coli membrane and purified phosphatidylcholine from egg yolk."}
{"id": "PMID:201611", "title": "On the reaction of cyanide with an oxygenated form of cytochrome oxidase.", "content": "The reaction of an oxygenated form of cytochrome oxidase [EC 1.9.3.1] with cyanide was examined under conditions where spontaneous decay was prevented. The equilibrium and kinetic constants for the reaction agreed well with those for the normally operating enzyme, indicating that the oxygenated form is one of the active intermediates of the cytochrome oxidase reaction.", "contents": "On the reaction of cyanide with an oxygenated form of cytochrome oxidase. The reaction of an oxygenated form of cytochrome oxidase [EC 1.9.3.1] with cyanide was examined under conditions where spontaneous decay was prevented. The equilibrium and kinetic constants for the reaction agreed well with those for the normally operating enzyme, indicating that the oxygenated form is one of the active intermediates of the cytochrome oxidase reaction."}
{"id": "PMID:201612", "title": "Degradation of benzenesulfonate to sulfite in bacterial extract.", "content": "Sulfite formation from benzenesulfonate was studied in extracts from a bacterium grown on this compound as a main carbon source. The activity of sulfite formation depended on the presence of NADH and oxygen as well as magnesium, suggesting an oxygenation-type reaction. The activity was found in a fraction precipitated by ammonium sulfate at 35-50% saturation; the specific activity was 15 times higher than that of crude extract, probably due to the elimination of inhibitory substances of low molecular weight from the preparation. In a distillate of the reaction mixture, phenol was found. Pyrocatechol as well as benzenesulfonate was oxidized in the crude extract, but phenol was not.", "contents": "Degradation of benzenesulfonate to sulfite in bacterial extract. Sulfite formation from benzenesulfonate was studied in extracts from a bacterium grown on this compound as a main carbon source. The activity of sulfite formation depended on the presence of NADH and oxygen as well as magnesium, suggesting an oxygenation-type reaction. The activity was found in a fraction precipitated by ammonium sulfate at 35-50% saturation; the specific activity was 15 times higher than that of crude extract, probably due to the elimination of inhibitory substances of low molecular weight from the preparation. In a distillate of the reaction mixture, phenol was found. Pyrocatechol as well as benzenesulfonate was oxidized in the crude extract, but phenol was not."}
{"id": "PMID:201613", "title": "1-Methoxy-5-methylphenazinium methyl sulfate. A photochemically stable electron mediator between NADH and various electron acceptors.", "content": "This paper describes the properties and application of 1-methoxy-5-methylphenazinium methyl sulfate (1-methoxyPMS), which is a photochemically stable, versatile electron carrier. Like 5-methylphenazinium methyl sulfate (PMS), it mediates electron transfer between NADH and various electron acceptors such as tetrazolium dyes or the electrode of an enzymic electric cell, and yet it does not deteriorate upon storage under scattered light in normal laboratories. The rate of reduction of 1-methoxyPMS coupled to the reoxidation of NADH produced by the lactate dehydrogenase reaction, was even faster than that of PMS. It was also successfully employed as an electron mediator in the enzymic electric cell method for the assay of NAD-linked dehydrogenases. 1-MethoxyPMS solution is rosy pink, and its standard redox potential (E0') is approximately +0.063 V. The use of 1-methoxyPMS will be beneficial in biochemistry as well as medical technology, where PMS has been used as an electron mediator in various electron transfer systems.", "contents": "1-Methoxy-5-methylphenazinium methyl sulfate. A photochemically stable electron mediator between NADH and various electron acceptors. This paper describes the properties and application of 1-methoxy-5-methylphenazinium methyl sulfate (1-methoxyPMS), which is a photochemically stable, versatile electron carrier. Like 5-methylphenazinium methyl sulfate (PMS), it mediates electron transfer between NADH and various electron acceptors such as tetrazolium dyes or the electrode of an enzymic electric cell, and yet it does not deteriorate upon storage under scattered light in normal laboratories. The rate of reduction of 1-methoxyPMS coupled to the reoxidation of NADH produced by the lactate dehydrogenase reaction, was even faster than that of PMS. It was also successfully employed as an electron mediator in the enzymic electric cell method for the assay of NAD-linked dehydrogenases. 1-MethoxyPMS solution is rosy pink, and its standard redox potential (E0') is approximately +0.063 V. The use of 1-methoxyPMS will be beneficial in biochemistry as well as medical technology, where PMS has been used as an electron mediator in various electron transfer systems."}
{"id": "PMID:201615", "title": "Definition of cytochrome c binding domains by chemical modification. II. Identification and properties of singly substituted carboxydinitrophenyl cytochromes c at lysines 8, 13, 22, 27, 39, 60, 72, 87, and 99.", "content": "Sensitive thin layer peptide mapping is employed to establish the identity and the homogeneity of eight singly substituted 4-carboxy-2,6-dinitrophenyl derivatives of horse cytochrome c. Seven of the components, all of greater than 95% homogeneity, are modified at lysyl residues 13, 72, 87, 8, 27, 39, and 60. The eighth component is a mixture of derivatives at lysines 22 and 99. The positions of the modified residues were confirmed by the amino acid analysis and Edman sequential degradation of the CDNP-peptides. Physiochemical properties characteristic of cytochrome c are unchanged in the chemically modified products examined. These properties, that include the proton NMR spectrum, are sensitive probes of the polypeptide organization surrounding the heme prosthetic group. The lack of any discernable changes indicates that modification of the epsilon-amino groups on the surface of cytochrome c does not perturb the overall structure of the protein. The widespread distribution of the modifications on the surface of the molecule, together with the homogeneity and native conformation of the CDNP-derivatives make them well suited for assessing the effects of changes in the charge topography on the electron transfer activity of cytochrome c.", "contents": "Definition of cytochrome c binding domains by chemical modification. II. Identification and properties of singly substituted carboxydinitrophenyl cytochromes c at lysines 8, 13, 22, 27, 39, 60, 72, 87, and 99. Sensitive thin layer peptide mapping is employed to establish the identity and the homogeneity of eight singly substituted 4-carboxy-2,6-dinitrophenyl derivatives of horse cytochrome c. Seven of the components, all of greater than 95% homogeneity, are modified at lysyl residues 13, 72, 87, 8, 27, 39, and 60. The eighth component is a mixture of derivatives at lysines 22 and 99. The positions of the modified residues were confirmed by the amino acid analysis and Edman sequential degradation of the CDNP-peptides. Physiochemical properties characteristic of cytochrome c are unchanged in the chemically modified products examined. These properties, that include the proton NMR spectrum, are sensitive probes of the polypeptide organization surrounding the heme prosthetic group. The lack of any discernable changes indicates that modification of the epsilon-amino groups on the surface of cytochrome c does not perturb the overall structure of the protein. The widespread distribution of the modifications on the surface of the molecule, together with the homogeneity and native conformation of the CDNP-derivatives make them well suited for assessing the effects of changes in the charge topography on the electron transfer activity of cytochrome c."}
{"id": "PMID:201617", "title": "Influence of potassium salt concentration and temperature on inhibition of mRNA translation by 7-methylguanosine5'-monophosphate.", "content": "The effect of 7-methylguanosine 5'-monophosphate (pm7G) on mRNA translation was examined in the wheat germ and rabbit reticulocyte cell-free systems. Differences between the two cell extracts with respect to inhibition of translation by pm7G can be attributed to different conditions commonly used for in vitro protein synthesis. Inhibition of globin mRNA translation by pm7G is strongly influenced by the concentration of potassium salt and to a lesser extent by incubation temperature. The effectiveness of the inhibitor increases with potassium salt concentration and diminishes with increasing temperature. Translation is inhibited by pm7G at physiological K+ concentration in both cell-free systems in that only the rate of binding of mRNA to ribosomes is affected by the inhibitor, not the extent of binding. Translation of different capped mRNAs is affected differently by pm7G, but this appears to be property of the mRNA rather than the translation system. These results indicate that while the 5'-terminal cap structure may be more important for translation of some mRNA's than others, this structure functions in translation of capped mRNAs in all types of cells.", "contents": "Influence of potassium salt concentration and temperature on inhibition of mRNA translation by 7-methylguanosine5'-monophosphate. The effect of 7-methylguanosine 5'-monophosphate (pm7G) on mRNA translation was examined in the wheat germ and rabbit reticulocyte cell-free systems. Differences between the two cell extracts with respect to inhibition of translation by pm7G can be attributed to different conditions commonly used for in vitro protein synthesis. Inhibition of globin mRNA translation by pm7G is strongly influenced by the concentration of potassium salt and to a lesser extent by incubation temperature. The effectiveness of the inhibitor increases with potassium salt concentration and diminishes with increasing temperature. Translation is inhibited by pm7G at physiological K+ concentration in both cell-free systems in that only the rate of binding of mRNA to ribosomes is affected by the inhibitor, not the extent of binding. Translation of different capped mRNAs is affected differently by pm7G, but this appears to be property of the mRNA rather than the translation system. These results indicate that while the 5'-terminal cap structure may be more important for translation of some mRNA's than others, this structure functions in translation of capped mRNAs in all types of cells."}
{"id": "PMID:201619", "title": "Properties of 2-nitropropane dioxygenase of Hansenula mrakii. Formation and participation of superoxide.", "content": "2-Nitropropane dioxygenase, purified to homogeneity from a yeast, Hansenula mrakii, is significantly inhibited by superoxide dismutase and various scavengers for superoxide anion such as cytochrome c, epinephrine, NADH, thiols, and polyhydric phenols. The reduction of cytochrome c and the oxidation of epinephrine and NADH are concomitant with the inhibition of enzymatic oxygenation. Neither the oxidation nor the reduction occursin the presence of superoxide dismutase or in the absence of 2-nitropropane or oxygen. Superoxide anion added externally induces the oxygenation. These findings indicate the generation of superoxide anion and its participation in the oxygenation of 2-nitropropane. The difference spectrum of the binding of NADH to 2-nitropropane dioxygenase exhibits a negative peak at 353 nm. One mole of NADH is bound to 1 mol of the enzyme and the pro-R hydrogen of the nicotinamide moiety of bound NADH predominantly is transferred to superoxide anion formed enzymatically or given externally. Thus, the diastereotopic hydrogen of NADH is discriminated by the enzyme, although not completely.", "contents": "Properties of 2-nitropropane dioxygenase of Hansenula mrakii. Formation and participation of superoxide. 2-Nitropropane dioxygenase, purified to homogeneity from a yeast, Hansenula mrakii, is significantly inhibited by superoxide dismutase and various scavengers for superoxide anion such as cytochrome c, epinephrine, NADH, thiols, and polyhydric phenols. The reduction of cytochrome c and the oxidation of epinephrine and NADH are concomitant with the inhibition of enzymatic oxygenation. Neither the oxidation nor the reduction occursin the presence of superoxide dismutase or in the absence of 2-nitropropane or oxygen. Superoxide anion added externally induces the oxygenation. These findings indicate the generation of superoxide anion and its participation in the oxygenation of 2-nitropropane. The difference spectrum of the binding of NADH to 2-nitropropane dioxygenase exhibits a negative peak at 353 nm. One mole of NADH is bound to 1 mol of the enzyme and the pro-R hydrogen of the nicotinamide moiety of bound NADH predominantly is transferred to superoxide anion formed enzymatically or given externally. Thus, the diastereotopic hydrogen of NADH is discriminated by the enzyme, although not completely."}
{"id": "PMID:201622", "title": "Heme is necessary for the accumulation and assembly of cytochrome c oxidase subunits in Saccharomyces cerevisiae.", "content": "The presence of cytochrome c oxidase subunits and the association of these subunits with each other was studied in a heme-deficient Saccharomyces cerevisiae mutant. This mutant had been isolated by Gollub et al. (1977) J. Biol. Chem. 252, 2846-2854) and had been shown lack delta-aminolevulinic acid synthetase. When grown in the absence of heme or heme precursors, the mutant is respiration-deficient, devoid of cytochrome absorption bands and auxotrophic for all those components whose biosynthesis is dependent on hemoproteins; when grown in the presence of heme or heme precursors, the mutant is phenotypically wild type. Upon growth of the mutant in the absence of heme synthesis, the mitochondria still contained two of the three mitochondrially made cytochrome c oxidase subunits (i.e. II and III) and at least one of the cytoplasmically made cytochrome c subunits (VI). The other subunits were either barely detectable (I, IV) or undetectable (V, VII). The residual subunits were apparently not assembled with each other since an antiserum directed mainly against Subunit VI failed to co-precipitate Subunits II and III which were still present. In contrast, growth of the mutant in the presence of delta-aminolevulinic acid led to the accumulation of active, fully assembled cytochrome c oxidase in the mitochondria. Heme a (or one of its precursors) thus controls the assembly of cytochrome c oxidase from its individual subunits.", "contents": "Heme is necessary for the accumulation and assembly of cytochrome c oxidase subunits in Saccharomyces cerevisiae. The presence of cytochrome c oxidase subunits and the association of these subunits with each other was studied in a heme-deficient Saccharomyces cerevisiae mutant. This mutant had been isolated by Gollub et al. (1977) J. Biol. Chem. 252, 2846-2854) and had been shown lack delta-aminolevulinic acid synthetase. When grown in the absence of heme or heme precursors, the mutant is respiration-deficient, devoid of cytochrome absorption bands and auxotrophic for all those components whose biosynthesis is dependent on hemoproteins; when grown in the presence of heme or heme precursors, the mutant is phenotypically wild type. Upon growth of the mutant in the absence of heme synthesis, the mitochondria still contained two of the three mitochondrially made cytochrome c oxidase subunits (i.e. II and III) and at least one of the cytoplasmically made cytochrome c subunits (VI). The other subunits were either barely detectable (I, IV) or undetectable (V, VII). The residual subunits were apparently not assembled with each other since an antiserum directed mainly against Subunit VI failed to co-precipitate Subunits II and III which were still present. In contrast, growth of the mutant in the presence of delta-aminolevulinic acid led to the accumulation of active, fully assembled cytochrome c oxidase in the mitochondria. Heme a (or one of its precursors) thus controls the assembly of cytochrome c oxidase from its individual subunits."}
{"id": "PMID:201624", "title": "Evidence for structural homology between human red cell phosphoglycerate mutase and 2,3-bisphosphoglycerate synthase.", "content": "Previous reports have suggested the possibility of extensive structural homology between human erythrocyte bisphosphoglycerate synthase (glycerate-1,3-P2 leads to glycerate-2,3-P2) and phosphoglycerate mutase (glycerate-3-P in equilibrium glycerate-2-P). This study lends credence to that conjecture through comparative physicochemical investigations involving peptide mapping, circular dichroism, and immunological techniques. The data indicate that despite differences in function, both enzymes apparently manifest a high degree of similarity in primary, secondary, and tertiary structure. Mapping data also indicate that each protein is comprised of two apparently identical subunits.", "contents": "Evidence for structural homology between human red cell phosphoglycerate mutase and 2,3-bisphosphoglycerate synthase. Previous reports have suggested the possibility of extensive structural homology between human erythrocyte bisphosphoglycerate synthase (glycerate-1,3-P2 leads to glycerate-2,3-P2) and phosphoglycerate mutase (glycerate-3-P in equilibrium glycerate-2-P). This study lends credence to that conjecture through comparative physicochemical investigations involving peptide mapping, circular dichroism, and immunological techniques. The data indicate that despite differences in function, both enzymes apparently manifest a high degree of similarity in primary, secondary, and tertiary structure. Mapping data also indicate that each protein is comprised of two apparently identical subunits."}
{"id": "PMID:201626", "title": "Phosphorylation of cardiac troponin by guanosine 3':5'-monophosphate-dependent protein kinase.", "content": "Homogeneous cGMP-dependent protein kinase catalyzes the rapid incorporation of phosphate, specifically into the inhibitory subunit of purified cardiac troponin with a maximal incorporation of 1 mol of phosphate/mol of troponin. When troponin was incubated in the presence of both cGMP- and cAMP-dependent protein kinases, a maximal incorporation of 1 mol of phosphate/mol of troponin was observed which suggested phosphorylation of the same site by the two kinases. Both cyclic nucleotide-dependent kinases had similar Km values for troponin, but the Vmax value for the phosphorylation reaction catalyzed by cAMP-dependent protein kinase was 12-fold greater than the value obtained for cGMP-dependent protein kinase.", "contents": "Phosphorylation of cardiac troponin by guanosine 3':5'-monophosphate-dependent protein kinase. Homogeneous cGMP-dependent protein kinase catalyzes the rapid incorporation of phosphate, specifically into the inhibitory subunit of purified cardiac troponin with a maximal incorporation of 1 mol of phosphate/mol of troponin. When troponin was incubated in the presence of both cGMP- and cAMP-dependent protein kinases, a maximal incorporation of 1 mol of phosphate/mol of troponin was observed which suggested phosphorylation of the same site by the two kinases. Both cyclic nucleotide-dependent kinases had similar Km values for troponin, but the Vmax value for the phosphorylation reaction catalyzed by cAMP-dependent protein kinase was 12-fold greater than the value obtained for cGMP-dependent protein kinase."}
{"id": "PMID:201627", "title": "Purified cyclic GMP-dependent protein kinase catalyzes the phosphorylation of cardiac troponin inhibitory subunit (TN-1).", "content": "Cyclic AMP- and cGMP-dependent protein kinases catalyze the phosphorylation of cardiac troponin inhibitory subunit (TN-I). Unlike many substrates utilized by both kinases, TN-I is rapidly phosphorylated using relatively low concentrations of the cGMP-dependent protein kinase (0.01 to 0.1 micrometer). At low concentrations of cAMP- and cGMP-dependent protein kinases, approximately twice as much total phosphate is incorporated into TN-I using the cAMP-dependent enzyme. At higher enzyme concentrations, 1 mol of phosphate/mol of TN-I is found using either enzyme. Maximal levels of cAMP- and CGMP-dependent protein kinases do not catalyze additive phosphorylation, suggesting that the two enzymes catalyze the phosphorylation of the same site on TN-I. The results support the concept of overlapping substrate specificity for cAMP- and cGMP-dependent protein kinases, but suggest that cardiac troponin contains additional specificity determinants for the cGMP-dependent protein kinase not found in several other protein substrates.", "contents": "Purified cyclic GMP-dependent protein kinase catalyzes the phosphorylation of cardiac troponin inhibitory subunit (TN-1). Cyclic AMP- and cGMP-dependent protein kinases catalyze the phosphorylation of cardiac troponin inhibitory subunit (TN-I). Unlike many substrates utilized by both kinases, TN-I is rapidly phosphorylated using relatively low concentrations of the cGMP-dependent protein kinase (0.01 to 0.1 micrometer). At low concentrations of cAMP- and cGMP-dependent protein kinases, approximately twice as much total phosphate is incorporated into TN-I using the cAMP-dependent enzyme. At higher enzyme concentrations, 1 mol of phosphate/mol of TN-I is found using either enzyme. Maximal levels of cAMP- and CGMP-dependent protein kinases do not catalyze additive phosphorylation, suggesting that the two enzymes catalyze the phosphorylation of the same site on TN-I. The results support the concept of overlapping substrate specificity for cAMP- and cGMP-dependent protein kinases, but suggest that cardiac troponin contains additional specificity determinants for the cGMP-dependent protein kinase not found in several other protein substrates."}
{"id": "PMID:201628", "title": "Sequence homology of the Ca2+-dependent regulator of cyclic nucleotide phosphodiesterase from rat testis with other Ca2+-binding proteins.", "content": "A Ca2+-dependent regulator protein of cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.17) has previously been isolated from rat testis and shown to be a heat-stable, Ca2+-binding protein with a molecular weight of approximately 17,000. The Ca2+-dependent regulator protein is also structurally similar to troponin-C, the Ca2+-binding component of muscle troponin and Ca2+ mediator of muscle contraction. The present report describes a partial amino acid sequence of the Ca2+-dependent regulator. The protein (148 amino acids) is 50% homologous with skeletal muscle troponin-C, but is 11 residues shorter than the muscle protein. The Ca2+-dependent regulator protein has an NH2-terminal sequence of acetyl-Ala-Asp-Glu, a COOH-terminal sequence of Thr-Ala-Lys and 1 residue of epsilon-trimethyllysine located at position 115. All of these properties are distinct from those of other homologous Ca2+-binding proteins. These properties may account for the biological specificities demonstrated by these proteins as compared to the Ca2+-dependent regulator protein. Based on the sequence and a comparison of the Ca2+-dependent regulator protein to other calcium-binding proteins, our data support the view that all of these moecules contain common sequences, especially at their proposed metal-binding sites.", "contents": "Sequence homology of the Ca2+-dependent regulator of cyclic nucleotide phosphodiesterase from rat testis with other Ca2+-binding proteins. A Ca2+-dependent regulator protein of cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.17) has previously been isolated from rat testis and shown to be a heat-stable, Ca2+-binding protein with a molecular weight of approximately 17,000. The Ca2+-dependent regulator protein is also structurally similar to troponin-C, the Ca2+-binding component of muscle troponin and Ca2+ mediator of muscle contraction. The present report describes a partial amino acid sequence of the Ca2+-dependent regulator. The protein (148 amino acids) is 50% homologous with skeletal muscle troponin-C, but is 11 residues shorter than the muscle protein. The Ca2+-dependent regulator protein has an NH2-terminal sequence of acetyl-Ala-Asp-Glu, a COOH-terminal sequence of Thr-Ala-Lys and 1 residue of epsilon-trimethyllysine located at position 115. All of these properties are distinct from those of other homologous Ca2+-binding proteins. These properties may account for the biological specificities demonstrated by these proteins as compared to the Ca2+-dependent regulator protein. Based on the sequence and a comparison of the Ca2+-dependent regulator protein to other calcium-binding proteins, our data support the view that all of these moecules contain common sequences, especially at their proposed metal-binding sites."}
{"id": "PMID:201629", "title": "Effect of pressure and ionic strength on the self-association of Apo-A-I from the human high density lipoprotein complex.", "content": "The self-association of apo-A-I isolated from the human high density lipoprotein complex has been investigated by gel permeation chromatography and sedimentation equilibrium. The apparent weight average molecular weight (MWapp) versus Apo-A-I concentration profile was found to be sensitive to ionic strength and pressure; MWapp increased with increasing ionic strength and decreasing rotor speed. The data were consistent with a monomer-dimer-tetrameroctamer association shceme over all conditions investigated if a change in the partial specific volume of apo-A-I upon association of 5.5 x 10(-2) ml/g is postulated.", "contents": "Effect of pressure and ionic strength on the self-association of Apo-A-I from the human high density lipoprotein complex. The self-association of apo-A-I isolated from the human high density lipoprotein complex has been investigated by gel permeation chromatography and sedimentation equilibrium. The apparent weight average molecular weight (MWapp) versus Apo-A-I concentration profile was found to be sensitive to ionic strength and pressure; MWapp increased with increasing ionic strength and decreasing rotor speed. The data were consistent with a monomer-dimer-tetrameroctamer association shceme over all conditions investigated if a change in the partial specific volume of apo-A-I upon association of 5.5 x 10(-2) ml/g is postulated."}
{"id": "PMID:201632", "title": "Phosphodiesterase activator from rat kidney cortex.", "content": "Incubation of homogenates of rat renal cortex at 4 degrees resulted in increased cAMP phosphodiesterase activity; the increase was much more rapid in hypotonic medium than in one of physiological tonicity. cAMP phosphodiesterase activity did not increase with incubation of supernatant fractions (48,000 x g, 20 min) prepared from isotonic homogenates. Extraction of the isotonic particulate fraction with hypotonic buffer released an activator which increased cAMP phosphodiesterase activity of the supernatant fraction. The kidney phosphodiesterase activator differed from a heat-stable, calcium-dependent protein activator of phosphodiesterase in that it was destroyed by heating (90 degrees for 10 min) and was not inhibited by EGTA. The phosphodiesterases of rat renal cortex were partially resolved by chromatography on DEAE-Bio-Gel, and a cAMP phosphodiesterase that is sensitive to the kidney activator was identified. This phosphodiesterase was separable from that affected by a calcium-dependent phosphodiesterase activator from bovine brain and from cGMP-stimulated cAMP phosphodiesterase. As determined by sucrose density gradient centrifugation, after incubation with the kidney activator, the activated form of phosphodiesterase had a lower sedimentation velocity than did the unactivated form.", "contents": "Phosphodiesterase activator from rat kidney cortex. Incubation of homogenates of rat renal cortex at 4 degrees resulted in increased cAMP phosphodiesterase activity; the increase was much more rapid in hypotonic medium than in one of physiological tonicity. cAMP phosphodiesterase activity did not increase with incubation of supernatant fractions (48,000 x g, 20 min) prepared from isotonic homogenates. Extraction of the isotonic particulate fraction with hypotonic buffer released an activator which increased cAMP phosphodiesterase activity of the supernatant fraction. The kidney phosphodiesterase activator differed from a heat-stable, calcium-dependent protein activator of phosphodiesterase in that it was destroyed by heating (90 degrees for 10 min) and was not inhibited by EGTA. The phosphodiesterases of rat renal cortex were partially resolved by chromatography on DEAE-Bio-Gel, and a cAMP phosphodiesterase that is sensitive to the kidney activator was identified. This phosphodiesterase was separable from that affected by a calcium-dependent phosphodiesterase activator from bovine brain and from cGMP-stimulated cAMP phosphodiesterase. As determined by sucrose density gradient centrifugation, after incubation with the kidney activator, the activated form of phosphodiesterase had a lower sedimentation velocity than did the unactivated form."}
{"id": "PMID:201633", "title": "Transport of a nonphosphorylated nucleoside, 5'-deoxyadenosine, by murine leukemia L1210 cells.", "content": "The mode of transport of a nonphosphorylated adenosine analog, 5'-deoxyadenosine, was studied in murine leukemia L1210 cells. This compound is not subject to the action of intracellular nucleoside-trapping kinases, and its transport can be examined without regard for effects of experimental conditions on kinase activity. Accumulation of 5'-deoxyadenosine was rapid, and nonconcentrative, with equilibrium attained within 12 s at 37 degrees. Kinetic studies were carried out at 20 degrees. We found both a nonmediated (diffusion) and a mediated transport process. The latter had an apparent Km fo 115 micrometer, Vmax = 105 pmol/10(6) cells/min. Uptake of 5'-deoxyadenosine was inhibited by several heterologous nucleosides including adenosine, 2'-deoxyadenosine, thymine riboside, and inosine. Like 2'-deoxyadenosine, 5'-deoxyadenosine was more lipid-soluble than adenosine (from octanol/water partition studies). Compared with 5'-deoxyadenosine, adenosine had a much lower apparent Km (5 micrometer) and a higher Q10 over the 27-37 degrees range (3.0 versus 1.3). Data obtained with adenosine might, however, reflect properties of intracellular adenosine kinase interacting with a transport process.", "contents": "Transport of a nonphosphorylated nucleoside, 5'-deoxyadenosine, by murine leukemia L1210 cells. The mode of transport of a nonphosphorylated adenosine analog, 5'-deoxyadenosine, was studied in murine leukemia L1210 cells. This compound is not subject to the action of intracellular nucleoside-trapping kinases, and its transport can be examined without regard for effects of experimental conditions on kinase activity. Accumulation of 5'-deoxyadenosine was rapid, and nonconcentrative, with equilibrium attained within 12 s at 37 degrees. Kinetic studies were carried out at 20 degrees. We found both a nonmediated (diffusion) and a mediated transport process. The latter had an apparent Km fo 115 micrometer, Vmax = 105 pmol/10(6) cells/min. Uptake of 5'-deoxyadenosine was inhibited by several heterologous nucleosides including adenosine, 2'-deoxyadenosine, thymine riboside, and inosine. Like 2'-deoxyadenosine, 5'-deoxyadenosine was more lipid-soluble than adenosine (from octanol/water partition studies). Compared with 5'-deoxyadenosine, adenosine had a much lower apparent Km (5 micrometer) and a higher Q10 over the 27-37 degrees range (3.0 versus 1.3). Data obtained with adenosine might, however, reflect properties of intracellular adenosine kinase interacting with a transport process."}
{"id": "PMID:201634", "title": "Synthesis of photopigments and electron transport components in synchronous phototrophic cultures of Rhodopseudomonas sphaeroides.", "content": "The kinetics of synthesis and incorporation of the photosynthetic pigments and several of the major oxidative and photosynthetic electron transport components of Rhodopseudomonas sphaeroides have been studied during synchronous and asynchronous phototrophic growth. The photosynthetic pigments and cytochromes c and b, measured spectroscopically, exhibited continuous patterns of synthesis and incorporation into the membrane particulate fraction in both synchronous and asynchronous cultures. Succinic dehydrogenase and NADH-oxidase activities, present at low levelnous growth. In a previous paper, Leuking, D.R., Fraley, R.T., and Kaplan, S. ((1978) J. Biol. Chem. 253, 451-457) have shown that total cellular phospholipid is also accumulated discontinuously during synchronous growth. A continuously incorporated membrane component is thus subject to a wide variation in the membrane protein/lipid ratio. The significance of this ratio in regulating the activity of membrane proteins is discussed and the distinction between protein incorporation and function is drawn with particular reference to the photosynthetic pigments and cytochrome components and the oxidative activities measured. It is suggested that a dependence of membrane protein activity on the membrane protein to lipid ratio in vivo is of possible significance in the control of membrane synthesis and cell division.", "contents": "Synthesis of photopigments and electron transport components in synchronous phototrophic cultures of Rhodopseudomonas sphaeroides. The kinetics of synthesis and incorporation of the photosynthetic pigments and several of the major oxidative and photosynthetic electron transport components of Rhodopseudomonas sphaeroides have been studied during synchronous and asynchronous phototrophic growth. The photosynthetic pigments and cytochromes c and b, measured spectroscopically, exhibited continuous patterns of synthesis and incorporation into the membrane particulate fraction in both synchronous and asynchronous cultures. Succinic dehydrogenase and NADH-oxidase activities, present at low levelnous growth. In a previous paper, Leuking, D.R., Fraley, R.T., and Kaplan, S. ((1978) J. Biol. Chem. 253, 451-457) have shown that total cellular phospholipid is also accumulated discontinuously during synchronous growth. A continuously incorporated membrane component is thus subject to a wide variation in the membrane protein/lipid ratio. The significance of this ratio in regulating the activity of membrane proteins is discussed and the distinction between protein incorporation and function is drawn with particular reference to the photosynthetic pigments and cytochrome components and the oxidative activities measured. It is suggested that a dependence of membrane protein activity on the membrane protein to lipid ratio in vivo is of possible significance in the control of membrane synthesis and cell division."}
{"id": "PMID:201636", "title": "Reconstitution of the apoenzyme of cytochrome oxidase from Pseudomonas aeruginosa with heme d1 and other heme groups.", "content": "Cytochrome oxidase (EC 1.9.3.2) from Pseudomonas aeruginosa contains heme d1 and heme c in an equimolar ratio. The heme d1 can be removed from the enzyme with acidified acetone leaving an apoenzyme that contains heme c but has no oxidase activity. Reconstitution of the apoenzyme in neutral 6 M urea with heme d1 yields a reconstituted product which, after removal of the urea, has 90 to 100% of the oxidase activity of the native enzyme, a 1:1 molar ratio of the heme groups, and is indistinguishable from the native on the basis of its absorption spectral properties and its EPR spectrum. The apoenzyme can also be reconstituted with heme a, deuteroheme, hematoheme, mesoheme, and protoheme but only the heme a yields a product with any oxidase activity. The properties of these reconstituted products are compared.", "contents": "Reconstitution of the apoenzyme of cytochrome oxidase from Pseudomonas aeruginosa with heme d1 and other heme groups. Cytochrome oxidase (EC 1.9.3.2) from Pseudomonas aeruginosa contains heme d1 and heme c in an equimolar ratio. The heme d1 can be removed from the enzyme with acidified acetone leaving an apoenzyme that contains heme c but has no oxidase activity. Reconstitution of the apoenzyme in neutral 6 M urea with heme d1 yields a reconstituted product which, after removal of the urea, has 90 to 100% of the oxidase activity of the native enzyme, a 1:1 molar ratio of the heme groups, and is indistinguishable from the native on the basis of its absorption spectral properties and its EPR spectrum. The apoenzyme can also be reconstituted with heme a, deuteroheme, hematoheme, mesoheme, and protoheme but only the heme a yields a product with any oxidase activity. The properties of these reconstituted products are compared."}
{"id": "PMID:201638", "title": "Purification and properties of a heat-stable protein inhibitor of phosphoprotein phosphatase from rabbit liver.", "content": "A heat-stable protein inhibitor of phosphoprotein phosphatase has been purified to homogeneity from rabbit liver extract by heating to 95 degrees followed by ion exchange chromatography on DEAE-cellulose and gel filtration on Sephadex G-200. The purified inhibitor showed a single band when examined by gel electrophoresis S20, w and Stokes radius values were 1.45 and 25.5, respectively. Using these two values, the molecular weight and frictional ratio was calculated to be 15,500 and 3.40, respectively. The molecular weight determined by sodium dodecyl sulfate-gel electrophoresis was found to be 14,200. The inhibition of phosphoprotein phosphatase was linear up to 40% inhibition with respect to inhibitor was constant with time of incubation for at least 30 min. The optimum pH for the inhibition was between 6.8 and 7.6. A kinetic analysis of the effect of the inhibitor on the dephosphorylation of [32P]phosphorylase a by rabbit liver phosphoprotein phosphatase indicated a noncompetitive inhibition with respect to phosphorylase a. Purified liver inhibitor inhibited the phosphoprotein phosphatase activity in all rat tissues examined. Utilizing purified rabbit liver phosphoprotein phosphatase, the presence of inhibitor activity was also demonstrated in all rat tissues tested.", "contents": "Purification and properties of a heat-stable protein inhibitor of phosphoprotein phosphatase from rabbit liver. A heat-stable protein inhibitor of phosphoprotein phosphatase has been purified to homogeneity from rabbit liver extract by heating to 95 degrees followed by ion exchange chromatography on DEAE-cellulose and gel filtration on Sephadex G-200. The purified inhibitor showed a single band when examined by gel electrophoresis S20, w and Stokes radius values were 1.45 and 25.5, respectively. Using these two values, the molecular weight and frictional ratio was calculated to be 15,500 and 3.40, respectively. The molecular weight determined by sodium dodecyl sulfate-gel electrophoresis was found to be 14,200. The inhibition of phosphoprotein phosphatase was linear up to 40% inhibition with respect to inhibitor was constant with time of incubation for at least 30 min. The optimum pH for the inhibition was between 6.8 and 7.6. A kinetic analysis of the effect of the inhibitor on the dephosphorylation of [32P]phosphorylase a by rabbit liver phosphoprotein phosphatase indicated a noncompetitive inhibition with respect to phosphorylase a. Purified liver inhibitor inhibited the phosphoprotein phosphatase activity in all rat tissues examined. Utilizing purified rabbit liver phosphoprotein phosphatase, the presence of inhibitor activity was also demonstrated in all rat tissues tested."}
{"id": "PMID:201639", "title": "Cellular RNA synthesis in normal and mengovirus-infected L-929 cells.", "content": "Cellular RNA synthesis was studied in mouse L-929 cells and in these cells infected with mengovirus. RNA polymerases I, II, and III were partially purified and their chromatographic properties were analyzed by DEAE-Sephadex A-25 chromatography. RNA polymerase II was purified from mouse liver and its subunit structure was compared to that of normal and virus-infected L-929 cells by two-dimensional gel electrophoresis. By these criteria, the enzymes from all three sources were identical. The RNA synthetic activities and capacities of chromatins from normal and virus-infected cells were compared under a variety of conditions. The endogenous activity in chromatin from infected cells was inhibited relative to controls but the residual activity responded normally to stimulation by ammonium sulfate, heparin, and Sarkosyl. The template capacity of the chromatins was compared with added RNA polymerase II and by a rifampicin challenge assay utilizing Escherichia coli RNA polymerase. Identical results were obtained in each case. The number of growing RNA chains and the rates of their elongations were determined. The results showed that nuclei and chromatin from infected cells have a smaller number of RNA polymerase II molecules engaged in RNA synthesis than normal cells do but that the active molecules elongate RNA chains at the same rate.", "contents": "Cellular RNA synthesis in normal and mengovirus-infected L-929 cells. Cellular RNA synthesis was studied in mouse L-929 cells and in these cells infected with mengovirus. RNA polymerases I, II, and III were partially purified and their chromatographic properties were analyzed by DEAE-Sephadex A-25 chromatography. RNA polymerase II was purified from mouse liver and its subunit structure was compared to that of normal and virus-infected L-929 cells by two-dimensional gel electrophoresis. By these criteria, the enzymes from all three sources were identical. The RNA synthetic activities and capacities of chromatins from normal and virus-infected cells were compared under a variety of conditions. The endogenous activity in chromatin from infected cells was inhibited relative to controls but the residual activity responded normally to stimulation by ammonium sulfate, heparin, and Sarkosyl. The template capacity of the chromatins was compared with added RNA polymerase II and by a rifampicin challenge assay utilizing Escherichia coli RNA polymerase. Identical results were obtained in each case. The number of growing RNA chains and the rates of their elongations were determined. The results showed that nuclei and chromatin from infected cells have a smaller number of RNA polymerase II molecules engaged in RNA synthesis than normal cells do but that the active molecules elongate RNA chains at the same rate."}
{"id": "PMID:201640", "title": "Nucleotide sequence of the DNA encoding the 5'-terminal sequences of simian virus 40 late mRNA.", "content": "We have used a combination of techniques of DNA and RNA sequence analysis to determine the nucleotide sequence of the portion of simian virus 40 DNA preceding and encoding the 5' end of mRNA for the structural protein VP2 of simian virus 40. Comparison of the sequence with those found in polyadenylated RNA in the cytoplasm of infected cells RNA shows that the transcript of sequences preceding the structural gene is more abundant than the transcript containing the codons for the protein. Between the abundant transcript of sequences preceding the coding region and the less abundant transcript of the coding region there is a short sequence whose transcript is not detected.", "contents": "Nucleotide sequence of the DNA encoding the 5'-terminal sequences of simian virus 40 late mRNA. We have used a combination of techniques of DNA and RNA sequence analysis to determine the nucleotide sequence of the portion of simian virus 40 DNA preceding and encoding the 5' end of mRNA for the structural protein VP2 of simian virus 40. Comparison of the sequence with those found in polyadenylated RNA in the cytoplasm of infected cells RNA shows that the transcript of sequences preceding the structural gene is more abundant than the transcript containing the codons for the protein. Between the abundant transcript of sequences preceding the coding region and the less abundant transcript of the coding region there is a short sequence whose transcript is not detected."}
{"id": "PMID:201641", "title": "Nucleotides sequence of the genes for the simian virus 40 proteins VP2 and VP3.", "content": "We have determined the nucleotide sequence of the DNA of simian virus 40. The proceeding report (Dhar, R., Reddy, V.B., and Weissman, S.M. (1978) J. Biol. Chem. 253, 612-620) presents the sequence of a portion of the simian virus 40 DNA that overlaps the region encoding the 5' end of the minor structural protein VP2. We report here the sequence of the remainder of the genes for minor structural proteins VP2 and VP3. The results indicate that the mRNA for the two proteins is read in the same phase and the initiation site for VP3 lies within the structural gene of VP2. The codons of the COOH-terminal amino acids of VP2 and VP3 are read in a second phase as the codons of the NH2-terminal amino acids of VP1.", "contents": "Nucleotides sequence of the genes for the simian virus 40 proteins VP2 and VP3. We have determined the nucleotide sequence of the DNA of simian virus 40. The proceeding report (Dhar, R., Reddy, V.B., and Weissman, S.M. (1978) J. Biol. Chem. 253, 612-620) presents the sequence of a portion of the simian virus 40 DNA that overlaps the region encoding the 5' end of the minor structural protein VP2. We report here the sequence of the remainder of the genes for minor structural proteins VP2 and VP3. The results indicate that the mRNA for the two proteins is read in the same phase and the initiation site for VP3 lies within the structural gene of VP2. The codons of the COOH-terminal amino acids of VP2 and VP3 are read in a second phase as the codons of the NH2-terminal amino acids of VP1."}
{"id": "PMID:201644", "title": "A polymethacrylate-silica composite material for dental implants.", "content": "A study has been carried out on the structure and surface texture of a new dental implant material composed of silica microspheres (3 or 5 wt%) and poly(methyl methacrylate). A recently developed composite material composed of vitreous carbon microballoons and poly(methyl methacrylate) has proven highly successful in clinical use, but the black color presents aesthetic problems at the gingival margin. The new material was developed in order to reproduce the many desirable qualities of the vitreous carbon-polymethacrylate composite, while omitting the black color. Square wafers (10 mm X 10 mm X1 mm) were studied, with the surface sandblasted in half of the specimens. Light microscopy revealed an even spacing of spherical configurations throughout the material. Scanning electron microscope studies revealed a finely porous surface with many large craters in the sandblasted specimens.", "contents": "A polymethacrylate-silica composite material for dental implants. A study has been carried out on the structure and surface texture of a new dental implant material composed of silica microspheres (3 or 5 wt%) and poly(methyl methacrylate). A recently developed composite material composed of vitreous carbon microballoons and poly(methyl methacrylate) has proven highly successful in clinical use, but the black color presents aesthetic problems at the gingival margin. The new material was developed in order to reproduce the many desirable qualities of the vitreous carbon-polymethacrylate composite, while omitting the black color. Square wafers (10 mm X 10 mm X1 mm) were studied, with the surface sandblasted in half of the specimens. Light microscopy revealed an even spacing of spherical configurations throughout the material. Scanning electron microscope studies revealed a finely porous surface with many large craters in the sandblasted specimens."}
{"id": "PMID:201645", "title": "Sites of lipoprotein particles in normal rat hepatocytes.", "content": "Very low density lipoprotein (VLDL) particles are packaged by the Golgi apparatus into vacuoles which move to the plasma membrane and empty the particles into the space of Disse, via exocytosis. Traditionally, all lipoprotein-containing cisternae and vacuoles are thought to be parts of this pathway. Observations reported here demonstrate that there is a second population of lipoprotein-containing cisternae and vacuoles. This population is part of GERL, an organelle we consider to be a specialized hydrolase-rich region of the endoplasmic reticulum (ER). To our knowledge, this is the first systematic study of GERL in normal rat hepatocytes.", "contents": "Sites of lipoprotein particles in normal rat hepatocytes. Very low density lipoprotein (VLDL) particles are packaged by the Golgi apparatus into vacuoles which move to the plasma membrane and empty the particles into the space of Disse, via exocytosis. Traditionally, all lipoprotein-containing cisternae and vacuoles are thought to be parts of this pathway. Observations reported here demonstrate that there is a second population of lipoprotein-containing cisternae and vacuoles. This population is part of GERL, an organelle we consider to be a specialized hydrolase-rich region of the endoplasmic reticulum (ER). To our knowledge, this is the first systematic study of GERL in normal rat hepatocytes."}
{"id": "PMID:201646", "title": "Ultrastructural changes and cyclic AMP in frog oxyntic cells.", "content": "In vitro frog gastric mucosa was employed as a model for a combined physiological, biochemical, and ultrastructural study of the morphological changes which accompany the onset of acid secretion by the oxyntic cell. The histamine H2-receptor antagonist metiamide was used to provide a reproducible control state. Stimulation of acid production by theophylline resulted in a 10-fold increase in plasma membrane surface area and a distinct change in the conformation of mitochondrial cristae. Studies using the acid secretion inhibitors, thiocyanate and anoxia, demonstrated that neither acid production per se nor oxidative metabolism is essential for the theophylline-dependent changes in surface area. Increases in tissue cyclic AMP levels were observed under the conditions producing morphological changes. It is postulated that surface area changes induced by theophylline are controlled by cellular cyclic AMP levels.", "contents": "Ultrastructural changes and cyclic AMP in frog oxyntic cells. In vitro frog gastric mucosa was employed as a model for a combined physiological, biochemical, and ultrastructural study of the morphological changes which accompany the onset of acid secretion by the oxyntic cell. The histamine H2-receptor antagonist metiamide was used to provide a reproducible control state. Stimulation of acid production by theophylline resulted in a 10-fold increase in plasma membrane surface area and a distinct change in the conformation of mitochondrial cristae. Studies using the acid secretion inhibitors, thiocyanate and anoxia, demonstrated that neither acid production per se nor oxidative metabolism is essential for the theophylline-dependent changes in surface area. Increases in tissue cyclic AMP levels were observed under the conditions producing morphological changes. It is postulated that surface area changes induced by theophylline are controlled by cellular cyclic AMP levels."}
{"id": "PMID:201647", "title": "Reversible inhibition of the norepinephrine induction of lactate dehydrogenase by cytochalasin B in rat glial C6 cells.", "content": "The cyclic AMP mediated induction of lactate dehydrogenase (LDH: E.C. 1.1.1.27) activity by norepinephrine in the rat glial cell line C6 is inhibited by cytochalasin B. Doses of 5, 15, and 25 microgram/ml of cytochalasin B inhibited the induction equally. Twenty-five microgram/ml of cytochalasin B inhibited the induction reversibly, and had no effect on basal enzyme level. No effect of cytochalasin B on general protein synthesis was found, nor did it increase the rate of decline of enzyme activity in deinduced cells. It therefore appears to block LDH induction by selectivity inhibiting its synthesis. Cytochalasin B had no effect on the transient (intracellular and extracelllular) rise in cyclic AMP generated in response to norepinephrine treatment. Cytochalasin B was effective when added during the transcription dependent phase (first 3 hours) but not during the translation dependent phase (after 3 hours) of LDH induction. The suggestion is discussed that cytochalasin B inhibits one of the early events of the inductive process.", "contents": "Reversible inhibition of the norepinephrine induction of lactate dehydrogenase by cytochalasin B in rat glial C6 cells. The cyclic AMP mediated induction of lactate dehydrogenase (LDH: E.C. 1.1.1.27) activity by norepinephrine in the rat glial cell line C6 is inhibited by cytochalasin B. Doses of 5, 15, and 25 microgram/ml of cytochalasin B inhibited the induction equally. Twenty-five microgram/ml of cytochalasin B inhibited the induction reversibly, and had no effect on basal enzyme level. No effect of cytochalasin B on general protein synthesis was found, nor did it increase the rate of decline of enzyme activity in deinduced cells. It therefore appears to block LDH induction by selectivity inhibiting its synthesis. Cytochalasin B had no effect on the transient (intracellular and extracelllular) rise in cyclic AMP generated in response to norepinephrine treatment. Cytochalasin B was effective when added during the transcription dependent phase (first 3 hours) but not during the translation dependent phase (after 3 hours) of LDH induction. The suggestion is discussed that cytochalasin B inhibits one of the early events of the inductive process."}
{"id": "PMID:201648", "title": "The characterization of SV40-transformed cell lines derived from mouse teratocarcinoma: growth properties and differentiated characteristics.", "content": "Mouse teratocarcinoma cells derived from embryoid bodies of 129SVsl mice were cultured in vitro to permit their differentiation. These cells were then infected with simiam virus 40 (SV40) and 31 cloned cell lines (SVTER) were derived from these cultures. All 31 SVTER cell lines contained the SV40 tumor (T) antigen and grew as permanent lines in culture. Mock-infected embryoid body cultures did not give rise to permanent cell lines. The morphology of each SVTER cell line was distinct and did not change during successive subclonings. The growth properties and tumorigenic potential of all 31 SVTER cell lines were investigated. None of these lines produced tumors in 129SVsl mice. Each cell line was tested for its ability to (1) grow in medium containing 1% serum, (2) plate on cell monolayer, and (3) form clones in methocel suspension. Only three of the SVTER cell lines were transformed with respect to all three of these criteria. Most of these cell lines were minimal transformants. The SVTER cell lines were tested for creatine phospholinase (CPK), an enzyme activity chracteristic of mouse brain and muscle tissue, and the protease, plasminogen activator (PA) which is found in embryoid bodies  and several differentiated cell types. Some of the SVTER cell lines contained high levels of CPK, while others had high levels of PA and a third group of cells contained neither enzyme activity. No SVTER cell line was found with high levels of both these enzyme activities. This result suggests that mutually exclusive sets of genes are expressed in these cells as might be expected from the distinct tissue distribution of the two enzyme activities studied. These SVTER cell lines may be useful in reconstructing developmental pathways of differentiating teratomas in vitro.", "contents": "The characterization of SV40-transformed cell lines derived from mouse teratocarcinoma: growth properties and differentiated characteristics. Mouse teratocarcinoma cells derived from embryoid bodies of 129SVsl mice were cultured in vitro to permit their differentiation. These cells were then infected with simiam virus 40 (SV40) and 31 cloned cell lines (SVTER) were derived from these cultures. All 31 SVTER cell lines contained the SV40 tumor (T) antigen and grew as permanent lines in culture. Mock-infected embryoid body cultures did not give rise to permanent cell lines. The morphology of each SVTER cell line was distinct and did not change during successive subclonings. The growth properties and tumorigenic potential of all 31 SVTER cell lines were investigated. None of these lines produced tumors in 129SVsl mice. Each cell line was tested for its ability to (1) grow in medium containing 1% serum, (2) plate on cell monolayer, and (3) form clones in methocel suspension. Only three of the SVTER cell lines were transformed with respect to all three of these criteria. Most of these cell lines were minimal transformants. The SVTER cell lines were tested for creatine phospholinase (CPK), an enzyme activity chracteristic of mouse brain and muscle tissue, and the protease, plasminogen activator (PA) which is found in embryoid bodies  and several differentiated cell types. Some of the SVTER cell lines contained high levels of CPK, while others had high levels of PA and a third group of cells contained neither enzyme activity. No SVTER cell line was found with high levels of both these enzyme activities. This result suggests that mutually exclusive sets of genes are expressed in these cells as might be expected from the distinct tissue distribution of the two enzyme activities studied. These SVTER cell lines may be useful in reconstructing developmental pathways of differentiating teratomas in vitro."}
{"id": "PMID:201651", "title": "Dibutyryl cyclic AMP arrests the growth of cultivated Cloudman melanoma cells in the late S and G2 phases of the cell cycle.", "content": "DBcAMP reversibly arrests cultivated Cloudman melanoma cells in the late S and G2 phases of the cell cycle. This is supported by the measurement of DNA synthesis by autoradiography and measurement of cellular DNA by two methods--the diphenylamine reaction and microspectrophotometry of Feulgen stained cells. We also present evidence that (1) cell division is prevented if DBcAMP is added as late in the cycle as early S phase. (2) The inhibition of cell division does not appear to be caused by products of tyrosine oxidation. (3) The increase in cell size that occurs in the presence of DBcAMP reflects continued synthesis of protein in the absence of cell division.", "contents": "Dibutyryl cyclic AMP arrests the growth of cultivated Cloudman melanoma cells in the late S and G2 phases of the cell cycle. DBcAMP reversibly arrests cultivated Cloudman melanoma cells in the late S and G2 phases of the cell cycle. This is supported by the measurement of DNA synthesis by autoradiography and measurement of cellular DNA by two methods--the diphenylamine reaction and microspectrophotometry of Feulgen stained cells. We also present evidence that (1) cell division is prevented if DBcAMP is added as late in the cycle as early S phase. (2) The inhibition of cell division does not appear to be caused by products of tyrosine oxidation. (3) The increase in cell size that occurs in the presence of DBcAMP reflects continued synthesis of protein in the absence of cell division."}
{"id": "PMID:201653", "title": "Effects of cyclic AMP on the growth of differentiating and undifferentiated Friend erythroleukemic cells.", "content": "Elevated concentrations of cyclic AMP elicit only minor reductions in growth rate and saturation density in undifferentiated Friend erythroleukemic cells. During the course of dimethylsulfoxide (DMSO)-induced differentiation, Friend cells convert from a cyclic AMP-tolerant state to a phenotype characterized by a high degree of sensitivity to cyclic AMP-mediated growth arrest. Conversion to cyclic AMP sensitivity is detectable after 30 hours growth in medium containing 2% DMSO, and either 0.5 mM 8-Br-cyclic AMP or 5 nM cholera toxin. Cultures of differentiating Friend cells achieved a stationary phase density that was approximately 8-fold higher than the cell density observed in parallel, differentiating cultures treated with 0.5 mM 8-Br-cyclic AMP. Temporally, the appearance of cyclic AMP-sensitivity corresponds to the early expression of in vitro erythroid differentiation (Ross et al., '74), but growth arrest does not alter the subsequent accumulation of hemoglobin in non-dividing DMSO-induced cells. Since growth arrest is preceded by a round of cell division, these observations are consistent with the concept that DMSO must be present during DNA replication for the subsequent expression of hemoglobin synthesis (McClintock and Papaconstantinou, '74; Levy et al., '75; Harrison, '76).", "contents": "Effects of cyclic AMP on the growth of differentiating and undifferentiated Friend erythroleukemic cells. Elevated concentrations of cyclic AMP elicit only minor reductions in growth rate and saturation density in undifferentiated Friend erythroleukemic cells. During the course of dimethylsulfoxide (DMSO)-induced differentiation, Friend cells convert from a cyclic AMP-tolerant state to a phenotype characterized by a high degree of sensitivity to cyclic AMP-mediated growth arrest. Conversion to cyclic AMP sensitivity is detectable after 30 hours growth in medium containing 2% DMSO, and either 0.5 mM 8-Br-cyclic AMP or 5 nM cholera toxin. Cultures of differentiating Friend cells achieved a stationary phase density that was approximately 8-fold higher than the cell density observed in parallel, differentiating cultures treated with 0.5 mM 8-Br-cyclic AMP. Temporally, the appearance of cyclic AMP-sensitivity corresponds to the early expression of in vitro erythroid differentiation (Ross et al., '74), but growth arrest does not alter the subsequent accumulation of hemoglobin in non-dividing DMSO-induced cells. Since growth arrest is preceded by a round of cell division, these observations are consistent with the concept that DMSO must be present during DNA replication for the subsequent expression of hemoglobin synthesis (McClintock and Papaconstantinou, '74; Levy et al., '75; Harrison, '76)."}
{"id": "PMID:201654", "title": "The role of butyrate in the reverse transformation reaction in mammalian cells.", "content": "The reverse transformation reaction of Chinese hamster ovary cells from compact, epithelial-like, randomly growing, heavily knobbed, lectin reactive cells into stretched, tighly adherent, smooth-surfaced, lectin resistant, fibroblast-like cells normally elicited by dibutyryl cAMP can be produced to its complete extent by N6-monobutyryl cAMP or 8-bromo-cAMP, O2'-monobutyryl cAMP is ineffective as is cAMP itself in the absence of an inhibitor of phosphodiesterase activity. In the presence of a phosphodiesterase inhibitor, cAMP is fully effective. These results indicate that the role of the butyryl groups of dibutyryl cAMP and, especially, the N6-butyryl, in the reverse transformation reaction is protection of the cAMP analogue from degradation. Butyrate at concentrations of about 1 mM does produce a response which to some extent mimics that of cAMP analogues. The cells, however, fail to assume a fibroblastic-like shape, but rather become flattened. The butyrate effect is much slower and less readily reversible than that evoked by cAMP analogues. Butyrate produces an approximately 2-fold increase in intracellular cAMP levels. These results are consistent with the hypothesis that butyrate effects, in part, are mediated by AMP.", "contents": "The role of butyrate in the reverse transformation reaction in mammalian cells. The reverse transformation reaction of Chinese hamster ovary cells from compact, epithelial-like, randomly growing, heavily knobbed, lectin reactive cells into stretched, tighly adherent, smooth-surfaced, lectin resistant, fibroblast-like cells normally elicited by dibutyryl cAMP can be produced to its complete extent by N6-monobutyryl cAMP or 8-bromo-cAMP, O2'-monobutyryl cAMP is ineffective as is cAMP itself in the absence of an inhibitor of phosphodiesterase activity. In the presence of a phosphodiesterase inhibitor, cAMP is fully effective. These results indicate that the role of the butyryl groups of dibutyryl cAMP and, especially, the N6-butyryl, in the reverse transformation reaction is protection of the cAMP analogue from degradation. Butyrate at concentrations of about 1 mM does produce a response which to some extent mimics that of cAMP analogues. The cells, however, fail to assume a fibroblastic-like shape, but rather become flattened. The butyrate effect is much slower and less readily reversible than that evoked by cAMP analogues. Butyrate produces an approximately 2-fold increase in intracellular cAMP levels. These results are consistent with the hypothesis that butyrate effects, in part, are mediated by AMP."}
{"id": "PMID:201655", "title": "Oscillations and cell development in Dictyostelium discoideum stimulated by folic acid pulses.", "content": "Folic acid is known to be a chemoattractant of pre-aggregation cells of Dictyostelium discoideum. When supplied in pulses, folic acid induces biochemical oscillations and stimulates the development of pre-aggregation to aggregation-competent amoebae. The continuous supply of folic acid has no stimulatory effect. Folic-acid-induced oscillations are accompanied by periodic changes in the cyclic AMP concentration. Pulses of folic acid applied with rhythms between 7 and 11 min efficiently induce oscillations. In contrast, a rhythm of 2 min neither induces oscillations nor suppresses them. Cells start to oscillate with a rhythm of about 8 min. This inherent rhythm is independent of the inducing rhythm. Oscillating cells are less sensitive to folic acid than pre-oscillating ones. They respond only to high concentrations of folic acid which also interact with the oscillating system.", "contents": "Oscillations and cell development in Dictyostelium discoideum stimulated by folic acid pulses. Folic acid is known to be a chemoattractant of pre-aggregation cells of Dictyostelium discoideum. When supplied in pulses, folic acid induces biochemical oscillations and stimulates the development of pre-aggregation to aggregation-competent amoebae. The continuous supply of folic acid has no stimulatory effect. Folic-acid-induced oscillations are accompanied by periodic changes in the cyclic AMP concentration. Pulses of folic acid applied with rhythms between 7 and 11 min efficiently induce oscillations. In contrast, a rhythm of 2 min neither induces oscillations nor suppresses them. Cells start to oscillate with a rhythm of about 8 min. This inherent rhythm is independent of the inducing rhythm. Oscillating cells are less sensitive to folic acid than pre-oscillating ones. They respond only to high concentrations of folic acid which also interact with the oscillating system."}
{"id": "PMID:201656", "title": "Role of Ca2+ in preserving viability of Friend erythroleukaemic cells after ultramicroinjection.", "content": "Ca2+ facilitated the fusion by Sendai virus of Friend erythroleukaemic cells and Ehrlich ascites tumour cells but not that of hepatoma tissue culture cells. In the absence of Ca2+ Sendai virus caused the complete depletion of ATP and abolished protein synthesis in Friend erythro-leukaemic cells fused with each other. Addition of high concentrations of Ca2+ (10-20 mM) partially protected the cells from ATP depletion. After a further incubation of cells in complete medium plus 0.2 mM adenine, ATP levels and protein synthesis were restored to 60-85% of those of the untreated control. The protective effect of Ca2+ was used to improve the ultramicroinjection method which involves the fusion of human erythrocyte ghosts with cells. When human erythrocyte ghosts containing high K+ were fused with Friend erythroleukaemic cells in the presence of 10 mM Ca2+ ATP levels and protein synthesis after recovery were about 60-85% of the control. Friend erythroleukaemic cells subjected to ultramicroinjection under these conditions had a cloning efficiency of 75-95% of that of the untreated controls. In these experiments 70-100% of the cells had fused with ghosts. Induction of haemoglobin synthesis by dimethylsulphoxide was unimpaired in cells subjected to ultramicroinjection under the same conditions.", "contents": "Role of Ca2+ in preserving viability of Friend erythroleukaemic cells after ultramicroinjection. Ca2+ facilitated the fusion by Sendai virus of Friend erythroleukaemic cells and Ehrlich ascites tumour cells but not that of hepatoma tissue culture cells. In the absence of Ca2+ Sendai virus caused the complete depletion of ATP and abolished protein synthesis in Friend erythro-leukaemic cells fused with each other. Addition of high concentrations of Ca2+ (10-20 mM) partially protected the cells from ATP depletion. After a further incubation of cells in complete medium plus 0.2 mM adenine, ATP levels and protein synthesis were restored to 60-85% of those of the untreated control. The protective effect of Ca2+ was used to improve the ultramicroinjection method which involves the fusion of human erythrocyte ghosts with cells. When human erythrocyte ghosts containing high K+ were fused with Friend erythroleukaemic cells in the presence of 10 mM Ca2+ ATP levels and protein synthesis after recovery were about 60-85% of the control. Friend erythroleukaemic cells subjected to ultramicroinjection under these conditions had a cloning efficiency of 75-95% of that of the untreated controls. In these experiments 70-100% of the cells had fused with ghosts. Induction of haemoglobin synthesis by dimethylsulphoxide was unimpaired in cells subjected to ultramicroinjection under the same conditions."}
{"id": "PMID:201658", "title": "Dynamics and characterization of plasma immunoreactive beta-melanocyte stimulating hormone in hemodialysis patients: its relationship to ACTH.", "content": "We studied the plasma immunoreactive beta-MSH (\"beta-MSH\") in hemodialysis patients to determine its basal level, plasma disappearance rate, gel filtration and immunological characteristics. All patients had increased plasma \"beta-MSH\" (90--440 pg/ml; normal less than 90 pg/ml). Plasma ACTH and cortisol values were within the normal range. Cortisol infusion over 2 h induced almost no plasma \"beta-MSH\" variation as compared to controls where \"beta-MSH\" decreased rapidly (apparent half-life 90 min.); more prolonged administration of corticosteroids (dexamethasone 0.5 mg every 6 h for two days) caused a slight (20%) but significant (P less than 0.001) decrease of \"beta-MSH.\" On Sephadex G-50 endogenous \"beta-MSH\" eluted in a molecular weight range of 6,000--10,000. In our radioimmunoassay dilution curves of endogenous \"beta-MSH\" paralleled that of synthetic human beta-MSH, but not that of purified human beta-LPH. In conclusion, hemodialysis patients show a clear dissociation between elevated \"beta-MSH\" and normal ACTH plasma levels. \"beta-MSH\" probably has a decreased plasma disappearance rate and seems related to a substance different from human beta-MSH.", "contents": "Dynamics and characterization of plasma immunoreactive beta-melanocyte stimulating hormone in hemodialysis patients: its relationship to ACTH. We studied the plasma immunoreactive beta-MSH (\"beta-MSH\") in hemodialysis patients to determine its basal level, plasma disappearance rate, gel filtration and immunological characteristics. All patients had increased plasma \"beta-MSH\" (90--440 pg/ml; normal less than 90 pg/ml). Plasma ACTH and cortisol values were within the normal range. Cortisol infusion over 2 h induced almost no plasma \"beta-MSH\" variation as compared to controls where \"beta-MSH\" decreased rapidly (apparent half-life 90 min.); more prolonged administration of corticosteroids (dexamethasone 0.5 mg every 6 h for two days) caused a slight (20%) but significant (P less than 0.001) decrease of \"beta-MSH.\" On Sephadex G-50 endogenous \"beta-MSH\" eluted in a molecular weight range of 6,000--10,000. In our radioimmunoassay dilution curves of endogenous \"beta-MSH\" paralleled that of synthetic human beta-MSH, but not that of purified human beta-LPH. In conclusion, hemodialysis patients show a clear dissociation between elevated \"beta-MSH\" and normal ACTH plasma levels. \"beta-MSH\" probably has a decreased plasma disappearance rate and seems related to a substance different from human beta-MSH."}
{"id": "PMID:201660", "title": "Cure of Cushing's disease by transsphenoidal removal of a microadenoma from a pituitary gland despite a radiographically normal sella turcica.", "content": "A 37-year-old woman had symptoms of Cushing's disease for two years. Galactorrhea was present. The diagnosis was confirmed by finding intermittently elevated urinary 17-hydroxysteroids, absent circadian rhythm, and elevated plasma ACTH. Plasma prolactin was slightly elevated. Films of the sella turcica were normal. A 9 mm basophilic microadenoma was removed by the transphenoidal approach. Immunocytochemical and electron-microscopic studies showed that the tumor was composed exclusively of ACTH secreting cells. Endocrine re-evaluation one year later revealed normal adrenal function. Serum prolactin had returned to normal. This case provides further evidence that Cushing's disease can be caused by a pituitary microadenoma insufficient in size to deform the sella.", "contents": "Cure of Cushing's disease by transsphenoidal removal of a microadenoma from a pituitary gland despite a radiographically normal sella turcica. A 37-year-old woman had symptoms of Cushing's disease for two years. Galactorrhea was present. The diagnosis was confirmed by finding intermittently elevated urinary 17-hydroxysteroids, absent circadian rhythm, and elevated plasma ACTH. Plasma prolactin was slightly elevated. Films of the sella turcica were normal. A 9 mm basophilic microadenoma was removed by the transphenoidal approach. Immunocytochemical and electron-microscopic studies showed that the tumor was composed exclusively of ACTH secreting cells. Endocrine re-evaluation one year later revealed normal adrenal function. Serum prolactin had returned to normal. This case provides further evidence that Cushing's disease can be caused by a pituitary microadenoma insufficient in size to deform the sella."}
{"id": "PMID:201661", "title": "Enzymatic and hemolytic properties of Propionibacterium acnes and related bacteria.", "content": "The production of chondroitin sulfatase, hyaluronidase, deoxyribonuclease, gelatinase, phosphatase, lecithinase, and hemolysins was examined in 95 strains of Propionibacterium acnes and four related species of anaerobic, respectively, microaerophilic coryneform bacteria (P. avidum, P. lymphophilum, P. granulosum, and Corynebacterium minutissimum). All enzymes could be demonstrated in at least one representative of the species tested. Those Propionibacterium species most frequently found in acne vulgaris lesions, i.e., P. acnes and P. granulosum, proved to be the most active organisms concerning the production of the enzymes tested. P. avidum, on the other hand, showed the highest rate of hemolytic activity.", "contents": "Enzymatic and hemolytic properties of Propionibacterium acnes and related bacteria. The production of chondroitin sulfatase, hyaluronidase, deoxyribonuclease, gelatinase, phosphatase, lecithinase, and hemolysins was examined in 95 strains of Propionibacterium acnes and four related species of anaerobic, respectively, microaerophilic coryneform bacteria (P. avidum, P. lymphophilum, P. granulosum, and Corynebacterium minutissimum). All enzymes could be demonstrated in at least one representative of the species tested. Those Propionibacterium species most frequently found in acne vulgaris lesions, i.e., P. acnes and P. granulosum, proved to be the most active organisms concerning the production of the enzymes tested. P. avidum, on the other hand, showed the highest rate of hemolytic activity."}
{"id": "PMID:201662", "title": "Use of immunoperoxidase for rapid diagnosis of mucocutaneous herpes simplex virus infection.", "content": "The indirect immunoperoxidase method was applied to the rapid diagnosis of mucocutaneous herpes simplex virus infection. Specimens were obtained directly from lesions at various stages in their evolution. The immunoperoxidase method identified herpes simplex virus-infected cells in 91% of vesicular lesions which were positive by standard virological culture. At later stages, the number of cases that could be diagnosed decreased appreciably. The immunoperoxidase method appears to be a rapid and reliable method for the diagnosis of early herpes simplex virus infection.", "contents": "Use of immunoperoxidase for rapid diagnosis of mucocutaneous herpes simplex virus infection. The indirect immunoperoxidase method was applied to the rapid diagnosis of mucocutaneous herpes simplex virus infection. Specimens were obtained directly from lesions at various stages in their evolution. The immunoperoxidase method identified herpes simplex virus-infected cells in 91% of vesicular lesions which were positive by standard virological culture. At later stages, the number of cases that could be diagnosed decreased appreciably. The immunoperoxidase method appears to be a rapid and reliable method for the diagnosis of early herpes simplex virus infection."}
{"id": "PMID:201663", "title": "Rotavirus isolation and cultivation in the presence of trypsin.", "content": "Rotaviruses are generally difficult to isolate and culture in vitro; therefore, virus isolation has not been used as a method of diagnosing this group of agents. The present report describes a simple procedure for isolating bovine rotaviruses directly from feces after pretreatment of fecal samples with trypsin. This procedure resulted in virus isolation from five of five samples that contained virus particles, as demonstrated by electron microscopy, and four of seven samples where virus particles could not be observed but were considered positive by the presence of immunofluorescent-staining cells in feces. Virus could not be isolated from \"normal\" feces. If the virus was not passaged in the presence of trypsin, the infectivity was gradually lost, but infectivity could be restored again if trypsin was added, resulting in increased virus spread and concomitant increase in virus yield. The application of this technique as a diagnostic tool for bovine and other rotaviruses is briefly discussed.", "contents": "Rotavirus isolation and cultivation in the presence of trypsin. Rotaviruses are generally difficult to isolate and culture in vitro; therefore, virus isolation has not been used as a method of diagnosing this group of agents. The present report describes a simple procedure for isolating bovine rotaviruses directly from feces after pretreatment of fecal samples with trypsin. This procedure resulted in virus isolation from five of five samples that contained virus particles, as demonstrated by electron microscopy, and four of seven samples where virus particles could not be observed but were considered positive by the presence of immunofluorescent-staining cells in feces. Virus could not be isolated from \"normal\" feces. If the virus was not passaged in the presence of trypsin, the infectivity was gradually lost, but infectivity could be restored again if trypsin was added, resulting in increased virus spread and concomitant increase in virus yield. The application of this technique as a diagnostic tool for bovine and other rotaviruses is briefly discussed."}
{"id": "PMID:201664", "title": "Anti-complement immunofluorescence test for antibodies to human cytomegalovirus.", "content": "An anti-complement immunofluorescence (ACIF) test that detects human cytomegalovirus (CMV) antigen in the nuclei of infected cells was used for assay of CMV antibodies in human sera. Various factors influencing the sensitivity and specificity of the ACIF test system were investigated, and results were applied to the development of a procedure which could be completed in a relatively short length of time and gave reproducible results. Results obtained in the ACIF test were compared with those obtained in complement fixation, indirect hemagglutination, and neutralization tests, and the ACIF test was shown to be suitable for detection of significant antibody titer rises and stationary levels of CMV antibody. Heterotypic antibody responses were not seen with sera from other human herpesvirus infections. The nonspecific cytoplasmic staining that occurs in indirect immunofluorescence tests for CMV did not occur in the ACIF system, and sera that were anti-complementary in complement fixation tests could be examined satisfactorily by ACIF. Thus, the test is a valuable supplemental or back-up procedure for the serodiagnosis of CMV infection.", "contents": "Anti-complement immunofluorescence test for antibodies to human cytomegalovirus. An anti-complement immunofluorescence (ACIF) test that detects human cytomegalovirus (CMV) antigen in the nuclei of infected cells was used for assay of CMV antibodies in human sera. Various factors influencing the sensitivity and specificity of the ACIF test system were investigated, and results were applied to the development of a procedure which could be completed in a relatively short length of time and gave reproducible results. Results obtained in the ACIF test were compared with those obtained in complement fixation, indirect hemagglutination, and neutralization tests, and the ACIF test was shown to be suitable for detection of significant antibody titer rises and stationary levels of CMV antibody. Heterotypic antibody responses were not seen with sera from other human herpesvirus infections. The nonspecific cytoplasmic staining that occurs in indirect immunofluorescence tests for CMV did not occur in the ACIF system, and sera that were anti-complementary in complement fixation tests could be examined satisfactorily by ACIF. Thus, the test is a valuable supplemental or back-up procedure for the serodiagnosis of CMV infection."}
{"id": "PMID:201665", "title": "Evaluation of anti-complement immunofluorescence test in cytomegalovirus infection.", "content": "The anti-complement immunofluorescence (ACIF) technique was evaluated for the diagnosis of human cytomegalovirus (CMV) infection in a group of sera derived from renal transplant recipients and donors by comparing it with the indirect immunofluorescence (FA) and complement fixation (CF) TESTS. The ACIF and FA tests yielded similar results. However, the ACIF test had a distinct advantage over the indirect FA test, since it eliminated the nonspecific cytoplasmic staining that may result in false positive readings in inexperienced hands. Both the indirect FA and ACIF tests were more sensitive than the CF test. In primary CMV infection, the FA and ACIF antibodies appeared earlier and had significantly higher titer than corresponding CF titers. This difference in titers was not seen in seropositive individuals who lacked overt infection. Our previously reported correlation between the seropositivity of the donor and CMV infection in seronegative recipients has been confirmed.", "contents": "Evaluation of anti-complement immunofluorescence test in cytomegalovirus infection. The anti-complement immunofluorescence (ACIF) technique was evaluated for the diagnosis of human cytomegalovirus (CMV) infection in a group of sera derived from renal transplant recipients and donors by comparing it with the indirect immunofluorescence (FA) and complement fixation (CF) TESTS. The ACIF and FA tests yielded similar results. However, the ACIF test had a distinct advantage over the indirect FA test, since it eliminated the nonspecific cytoplasmic staining that may result in false positive readings in inexperienced hands. Both the indirect FA and ACIF tests were more sensitive than the CF test. In primary CMV infection, the FA and ACIF antibodies appeared earlier and had significantly higher titer than corresponding CF titers. This difference in titers was not seen in seropositive individuals who lacked overt infection. Our previously reported correlation between the seropositivity of the donor and CMV infection in seronegative recipients has been confirmed."}
{"id": "PMID:201666", "title": "Improved glycine-extracted complement-fixing antigen for human cytomegalovirus.", "content": "High-titered, sensitive, and stable complement-fixing antigens for human cytomegalovirus were consistently produced from human diploid fibroblast cells infected at a high multiplicity of virus, harvested after 7 days of incubation, and sonically treated immediately in 0.1 M glycine buffer, pH 9.5.", "contents": "Improved glycine-extracted complement-fixing antigen for human cytomegalovirus. High-titered, sensitive, and stable complement-fixing antigens for human cytomegalovirus were consistently produced from human diploid fibroblast cells infected at a high multiplicity of virus, harvested after 7 days of incubation, and sonically treated immediately in 0.1 M glycine buffer, pH 9.5."}
{"id": "PMID:201667", "title": "Mechanisms contributing to malignant dysrhythmias induced by ischemia in the cat.", "content": "Continuously recorded bipolar electrograms were obtained simultaneously from epi-, endo-, and mid-myocardial regions of the ischemic and normal zones of cat left ventricle in vivo after coronary occlusion, analyzed by computer, and compared to regional cyclic AMP levels. Regional cyclic AMP content was used as an index of the combined local effects of: (a) efferent sympathetic nerve discharge; (b) release of myocardial catecholamines due to ischemia; and (c) circulating catecholamines. Ischemia resulted in a progressive increase in pulse width and rise time and a decrease in rate of rise of voltage (dV/dt) of the local electrograms from ischemic zones reaching a maximum within 2.4+/-0.3 min (mean+/-SE) at the time of onset of severe ventricular dysrhythmias, all of which returned toward control before the cessation of the dysrhythmia (33.5+/-1.5 min after coronary occlusion). Increases in cyclic AMP in ischemic zones preceded corresponding increases in the frequency of premature ventricular complexes (PVCs). Propranolol inhibited the increases in cyclic AMP and reduced the frequency of PVCs in animals without ventricular fibrillation. In animals with ventricular fibrillation, cyclic AMP was significantly elevated in normal and ischemic zones compared to animals with PVCs only. Electrical induction of PVCs or ventricular fibrillation in ischemic and nonischemic hearts failed to increase cyclic AMP. The results suggest that the changes in regional adrenergic stimulation of the heart may contribute to perpetuation of ventricular dysrhythmia and the genesis of ventricular fibrillation early after the onset of myocardial ischemia.", "contents": "Mechanisms contributing to malignant dysrhythmias induced by ischemia in the cat. Continuously recorded bipolar electrograms were obtained simultaneously from epi-, endo-, and mid-myocardial regions of the ischemic and normal zones of cat left ventricle in vivo after coronary occlusion, analyzed by computer, and compared to regional cyclic AMP levels. Regional cyclic AMP content was used as an index of the combined local effects of: (a) efferent sympathetic nerve discharge; (b) release of myocardial catecholamines due to ischemia; and (c) circulating catecholamines. Ischemia resulted in a progressive increase in pulse width and rise time and a decrease in rate of rise of voltage (dV/dt) of the local electrograms from ischemic zones reaching a maximum within 2.4+/-0.3 min (mean+/-SE) at the time of onset of severe ventricular dysrhythmias, all of which returned toward control before the cessation of the dysrhythmia (33.5+/-1.5 min after coronary occlusion). Increases in cyclic AMP in ischemic zones preceded corresponding increases in the frequency of premature ventricular complexes (PVCs). Propranolol inhibited the increases in cyclic AMP and reduced the frequency of PVCs in animals without ventricular fibrillation. In animals with ventricular fibrillation, cyclic AMP was significantly elevated in normal and ischemic zones compared to animals with PVCs only. Electrical induction of PVCs or ventricular fibrillation in ischemic and nonischemic hearts failed to increase cyclic AMP. The results suggest that the changes in regional adrenergic stimulation of the heart may contribute to perpetuation of ventricular dysrhythmia and the genesis of ventricular fibrillation early after the onset of myocardial ischemia."}
{"id": "PMID:201668", "title": "Properties of the plasma very low and low density lipoproteins in Tangier disease.", "content": "The absence of normal high density lipoproteins (HDL) in Tangier disease is well established, but the properties of very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in this disorder have not been well defined. The profiles obtained by analytic ultracentrifugation and the chemical composition, morphology, and electrophoretic mobility of Tangier and normal VLDL and LDL were compared. Apolipoproteins were fractionated by gel chromatography and characterized by amino acid analysis, polyacrylamide-gel electrophoresis, and immunochemical reactivity. Concentrations of low density lipoproteins of S(f) (o) 0-12 were reduced in three of six Tangier plasmas studied by analytic ultracentrifugation. Accumulation of intermediate density lipoproteins (S(f) (o) 12-20) was not observed. Two subjects with hypertriglyceridemia had normal VLDL (S(f) (o) 20-400) levels, suggesting that abnormalities of chylomicron metabolism probably account for the hypertriglyceridemia frequently observed in this disorder. Tangier VLDL migrate more slowly than normal VLDL on paper electrophoresis, yet their morphology, gross chemical composition, and qualitative apolipoprotein content are similar. Quantitative abnormalities in C-apolipoproteins, however, were observed in Tangier VLDL. When patients were consuming unrestricted diets, C apoproteins accounted for 19-49% of the protein in lipoproteins of d < 1.006 g/ml. Ingestion of low-fat, high-carbohydrate diets reduced the VLDL-C-apoprotein content in all Tangier patients (mean = 17% of VLDL protein vs. 43% in controls). These findings suggested that a major proportion of the C apoproteins in Tangier plasma is associated with chylomicrons or their remnants, perhaps because the C-apoprotein reservoir normally provided by HDL is absent. This secondary mechanism for C-apoprotein conservation is lost when dietary fat is withdrawn.LDL-2 (1.035 < d < 1.063) from Tangier and control plasma had identical electrophoretic mobilities. Tangier LDL-2 had slightly smaller median diameters (210-225 A vs. 230-240 A in controls) and a quite different composition than normal LDL-2. Triglyceride accounted for a mean of 29% of Tangier LDL-2 mass (control = 6%) and the cholesteryl ester content was reduced by about 50%. Thus, HDL may be required for the generation of chemically normal LDL. Alternatively, the fundamental defect in Tangier disease may involve all lipoprotein classes.", "contents": "Properties of the plasma very low and low density lipoproteins in Tangier disease. The absence of normal high density lipoproteins (HDL) in Tangier disease is well established, but the properties of very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in this disorder have not been well defined. The profiles obtained by analytic ultracentrifugation and the chemical composition, morphology, and electrophoretic mobility of Tangier and normal VLDL and LDL were compared. Apolipoproteins were fractionated by gel chromatography and characterized by amino acid analysis, polyacrylamide-gel electrophoresis, and immunochemical reactivity. Concentrations of low density lipoproteins of S(f) (o) 0-12 were reduced in three of six Tangier plasmas studied by analytic ultracentrifugation. Accumulation of intermediate density lipoproteins (S(f) (o) 12-20) was not observed. Two subjects with hypertriglyceridemia had normal VLDL (S(f) (o) 20-400) levels, suggesting that abnormalities of chylomicron metabolism probably account for the hypertriglyceridemia frequently observed in this disorder. Tangier VLDL migrate more slowly than normal VLDL on paper electrophoresis, yet their morphology, gross chemical composition, and qualitative apolipoprotein content are similar. Quantitative abnormalities in C-apolipoproteins, however, were observed in Tangier VLDL. When patients were consuming unrestricted diets, C apoproteins accounted for 19-49% of the protein in lipoproteins of d < 1.006 g/ml. Ingestion of low-fat, high-carbohydrate diets reduced the VLDL-C-apoprotein content in all Tangier patients (mean = 17% of VLDL protein vs. 43% in controls). These findings suggested that a major proportion of the C apoproteins in Tangier plasma is associated with chylomicrons or their remnants, perhaps because the C-apoprotein reservoir normally provided by HDL is absent. This secondary mechanism for C-apoprotein conservation is lost when dietary fat is withdrawn.LDL-2 (1.035 < d < 1.063) from Tangier and control plasma had identical electrophoretic mobilities. Tangier LDL-2 had slightly smaller median diameters (210-225 A vs. 230-240 A in controls) and a quite different composition than normal LDL-2. Triglyceride accounted for a mean of 29% of Tangier LDL-2 mass (control = 6%) and the cholesteryl ester content was reduced by about 50%. Thus, HDL may be required for the generation of chemically normal LDL. Alternatively, the fundamental defect in Tangier disease may involve all lipoprotein classes."}
{"id": "PMID:201669", "title": "Biologically active low density lipoprotein in human peripheral lymph.", "content": "We have compared the ability of human serum and peripheral lymph to suppress the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), to activate cholesteryl ester synthesis, and to compete with 125I-labeled low density lipoprotein (LDL) for binding to LDL receptors in cultured human fibroblasts. Whole lymph was active in all three tests and the activity per unit volume in lymph was approximately equal to 1/10th that in serum. All three biologic activities in lymph were confined to the d less than 1.063 g/ml fraction. Whole lymph had no significant effect on HMG-CoA reductase activity in fibroblasts from a patient with homozygous familial hypercholesterolemia, whose cells lack LDL receptors. The LDL-like biologic activity per unit mass of immunologically active apoprotein B was approximately the same in lymph as in serum. The current data indicate that functionally active LDL is present in lymph and that the concentration of this lipoprotein is approximately equal to 1/10th that in serum.", "contents": "Biologically active low density lipoprotein in human peripheral lymph. We have compared the ability of human serum and peripheral lymph to suppress the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), to activate cholesteryl ester synthesis, and to compete with 125I-labeled low density lipoprotein (LDL) for binding to LDL receptors in cultured human fibroblasts. Whole lymph was active in all three tests and the activity per unit volume in lymph was approximately equal to 1/10th that in serum. All three biologic activities in lymph were confined to the d less than 1.063 g/ml fraction. Whole lymph had no significant effect on HMG-CoA reductase activity in fibroblasts from a patient with homozygous familial hypercholesterolemia, whose cells lack LDL receptors. The LDL-like biologic activity per unit mass of immunologically active apoprotein B was approximately the same in lymph as in serum. The current data indicate that functionally active LDL is present in lymph and that the concentration of this lipoprotein is approximately equal to 1/10th that in serum."}
{"id": "PMID:201670", "title": "Astrovirus associated gastroenteritis in a children's ward.", "content": "During an outbreak of gastroenteritis in a paediatric ward astroviruses were found in faeces from 17 to 27 symptomatic children and from four of 14 members of the staff with diarrhoea. No viruses were found in 10 asymptomatic children. Fourteen of the 21 astrovirus excretors were free of any recognised pathogens, but in the other seven, rotaviruses or pathogenic bacteria were also present. Serological evidence of astrovirus infection was obtained in five adults and two children.", "contents": "Astrovirus associated gastroenteritis in a children's ward. During an outbreak of gastroenteritis in a paediatric ward astroviruses were found in faeces from 17 to 27 symptomatic children and from four of 14 members of the staff with diarrhoea. No viruses were found in 10 asymptomatic children. Fourteen of the 21 astrovirus excretors were free of any recognised pathogens, but in the other seven, rotaviruses or pathogenic bacteria were also present. Serological evidence of astrovirus infection was obtained in five adults and two children."}
{"id": "PMID:201671", "title": "Prolyl hydroxylase in the skin of patients with obstructive jaundice.", "content": "Prolyl hydroxylase was estimated in the skin of 24 jaundiced patients and 25 non-jaundiced patients. The activity of this enzyme was markedly reduced in the skin of the jaundiced patients.", "contents": "Prolyl hydroxylase in the skin of patients with obstructive jaundice. Prolyl hydroxylase was estimated in the skin of 24 jaundiced patients and 25 non-jaundiced patients. The activity of this enzyme was markedly reduced in the skin of the jaundiced patients."}
{"id": "PMID:201672", "title": "Multiple myeloma and oat cell carcinoma.", "content": "An association linking multiple myeloma with a higher incidence of carcinomatous tumours has been reported. The following case report describes a man diagnosed as having bronchogenic carcinoma found also to have myelomatosis. Aspects of this association are discussed.", "contents": "Multiple myeloma and oat cell carcinoma. An association linking multiple myeloma with a higher incidence of carcinomatous tumours has been reported. The following case report describes a man diagnosed as having bronchogenic carcinoma found also to have myelomatosis. Aspects of this association are discussed."}
{"id": "PMID:201679", "title": "Insulin stimulation of particulate, low Km adenosine 3',5'-monophosphate phosphodiesterase activity in fat cells of the obese-hyperglycemic (ob/ob) mouse.", "content": "Cyclic AMP phosphodiesterase activity was examined in particulate (30,000 X g for 30 min sediment) and supernatant subcellular fractions of epididymal fat cells isolated from obese-hyperglycemic (ob/ob) mice and their lean (+/?) LITTERMATES. The activity of the enzyme(s) was measured during both the early onset phase (5-6 weeks of age) and the static (5 months of age) of the obese-hyperglycemia syndrome. Fat cell particulate and supernate cyclic AMP phosphodiesterase activity of obese-hyperglycemic mice and their lean littermates at both ages displayed nonlinear Lineweaver-Burk kinetic plots. The maximum velocities of the fat cell particulate cyclic AMP phosphodiesterase activity of the obese mice were 67% and 84% lower than those of their lean littermates at 5-6 weeks and 5 months of age, respectively. Incubating fat cells obtained from either lean or obese mice of both age groups with 30 to 240 microunits of insulin per ml for 15 min increased the activity of the particulate, low Km cyclic AMP phosphodiesterase. This increase in activity was manifest as an increase in the maximum velocity of the enzyme(s) with no significant alteration of the affinity of the enzyme(s) for cyclic AMP.", "contents": "Insulin stimulation of particulate, low Km adenosine 3',5'-monophosphate phosphodiesterase activity in fat cells of the obese-hyperglycemic (ob/ob) mouse. Cyclic AMP phosphodiesterase activity was examined in particulate (30,000 X g for 30 min sediment) and supernatant subcellular fractions of epididymal fat cells isolated from obese-hyperglycemic (ob/ob) mice and their lean (+/?) LITTERMATES. The activity of the enzyme(s) was measured during both the early onset phase (5-6 weeks of age) and the static (5 months of age) of the obese-hyperglycemia syndrome. Fat cell particulate and supernate cyclic AMP phosphodiesterase activity of obese-hyperglycemic mice and their lean littermates at both ages displayed nonlinear Lineweaver-Burk kinetic plots. The maximum velocities of the fat cell particulate cyclic AMP phosphodiesterase activity of the obese mice were 67% and 84% lower than those of their lean littermates at 5-6 weeks and 5 months of age, respectively. Incubating fat cells obtained from either lean or obese mice of both age groups with 30 to 240 microunits of insulin per ml for 15 min increased the activity of the particulate, low Km cyclic AMP phosphodiesterase. This increase in activity was manifest as an increase in the maximum velocity of the enzyme(s) with no significant alteration of the affinity of the enzyme(s) for cyclic AMP."}
{"id": "PMID:201680", "title": "Properties of adenylate cyclase solubilized from rat adrenal membranes: effects of ACTH and other stimulators on solubilization.", "content": "We have solubilized adenylate cyclase in a relatively stable form from rat adrenal membranes. The solubilized enzyme elutes on a column of Sepharose 4BR as a distinct peak with a higher molecular weight than the soluble fractions which bind 125I-ACTH. Both the soluble and membrane bound enzymes are activated by NaF and Gpp(NH)p, and both have similar affinities for MgATP. While the membrane bound enzyme is activated similarly by either Mg2+ or Mn2+, the soluble enzyme is more fully activated by Mn2+. Pretreatment of adrenal membranes with NaF or Gpp(NH)p before the addition of detergent enhances recovery of soluble enzyme activity, while recovery of activity in the unsolubilized membrane pellet is unchanged. In contrast, addition of ACTH prevents solubilization of the enzyme and greatly increases its recovery in the pellet. This observation is consistent with the theory that action of the hormone on a receptor subunit leads to an association between the receptor and a catalytic subunit. Such an association might make it more difficult to remove the enzyme from the surrounding lipid matrix of the membrane.", "contents": "Properties of adenylate cyclase solubilized from rat adrenal membranes: effects of ACTH and other stimulators on solubilization. We have solubilized adenylate cyclase in a relatively stable form from rat adrenal membranes. The solubilized enzyme elutes on a column of Sepharose 4BR as a distinct peak with a higher molecular weight than the soluble fractions which bind 125I-ACTH. Both the soluble and membrane bound enzymes are activated by NaF and Gpp(NH)p, and both have similar affinities for MgATP. While the membrane bound enzyme is activated similarly by either Mg2+ or Mn2+, the soluble enzyme is more fully activated by Mn2+. Pretreatment of adrenal membranes with NaF or Gpp(NH)p before the addition of detergent enhances recovery of soluble enzyme activity, while recovery of activity in the unsolubilized membrane pellet is unchanged. In contrast, addition of ACTH prevents solubilization of the enzyme and greatly increases its recovery in the pellet. This observation is consistent with the theory that action of the hormone on a receptor subunit leads to an association between the receptor and a catalytic subunit. Such an association might make it more difficult to remove the enzyme from the surrounding lipid matrix of the membrane."}
{"id": "PMID:201681", "title": "Negative control of TSH action by iodide and acetylcholine: mechanism of action in intact thyroid cells.", "content": "Iodide, a substrate of thyroid metabolism, and acetylcholine depress cyclic AMP intracellular content and secretion in dog thyroid slices under TSH stimulation. A direct or indirect pseudocompetitive effect at the level of TSH receptor interaction has been rejected. Iodide and carbachol, both inhibited cyclic AMP accumulation in TSH stimulated dog thyroid slices but only the effect of carbachol was suppressed in the presence of isobutylmethylanthine. Ro 20-1724 did not relieve either inhibitory effect. Carbachol greatly enhanced cyclic AMP disposal in TSH prestimulated slices after the cut off of hormone action by a trypsin treatment. This effect was also suppressed by isobutylmethylxanthine but not by Ro 20-1724. No action of iodide could be evidenced on cyclic AMP disposal in similar slices, although a clear effect after the same time of iodide action was observed on cyclic AMP accumulation. Neither carbachol, nor iodide depresses ATP levels in these slices. The data suggest that carbachol exerts its action through an activation of cyclic AMP disappearance probably by an activation of cyclic AMP phosphodiesterase and that iodide, through an oxidized intermediate, experts its inhibitory effect at the level of cyclic AMP synthesis.", "contents": "Negative control of TSH action by iodide and acetylcholine: mechanism of action in intact thyroid cells. Iodide, a substrate of thyroid metabolism, and acetylcholine depress cyclic AMP intracellular content and secretion in dog thyroid slices under TSH stimulation. A direct or indirect pseudocompetitive effect at the level of TSH receptor interaction has been rejected. Iodide and carbachol, both inhibited cyclic AMP accumulation in TSH stimulated dog thyroid slices but only the effect of carbachol was suppressed in the presence of isobutylmethylanthine. Ro 20-1724 did not relieve either inhibitory effect. Carbachol greatly enhanced cyclic AMP disposal in TSH prestimulated slices after the cut off of hormone action by a trypsin treatment. This effect was also suppressed by isobutylmethylxanthine but not by Ro 20-1724. No action of iodide could be evidenced on cyclic AMP disposal in similar slices, although a clear effect after the same time of iodide action was observed on cyclic AMP accumulation. Neither carbachol, nor iodide depresses ATP levels in these slices. The data suggest that carbachol exerts its action through an activation of cyclic AMP disappearance probably by an activation of cyclic AMP phosphodiesterase and that iodide, through an oxidized intermediate, experts its inhibitory effect at the level of cyclic AMP synthesis."}
{"id": "PMID:201682", "title": "Effects of GTP on cyclic AMP concentrations in intact Ehrlich ascites tumor cells.", "content": "Experiments were conducted to test the hypothesis that intracellular concentrations of guanosine triphosphate (GTP) regulate the activity and hormonal sensitivity of adenylate cyclase in intact cells. By appropriate treatments, the GTP concentrations of Ehrlich ascites tumor cells could be varied between 28% and 680% of control values. Cyclic AMP concentrations were measured before and after addition of epinephrine in cells containing this range of GTP concentratins. Basal cyclic AMP concentrations were unaffected by changes in GTP concentrations. In cells containing lowered concentrations of GTP, the cyclic AMP concentration following addition of epinephrine was half that in control cells. Elevation of GTP concentrations above normal and had no effect on cyclic AMP concentrations following epinephrine treatment.", "contents": "Effects of GTP on cyclic AMP concentrations in intact Ehrlich ascites tumor cells. Experiments were conducted to test the hypothesis that intracellular concentrations of guanosine triphosphate (GTP) regulate the activity and hormonal sensitivity of adenylate cyclase in intact cells. By appropriate treatments, the GTP concentrations of Ehrlich ascites tumor cells could be varied between 28% and 680% of control values. Cyclic AMP concentrations were measured before and after addition of epinephrine in cells containing this range of GTP concentratins. Basal cyclic AMP concentrations were unaffected by changes in GTP concentrations. In cells containing lowered concentrations of GTP, the cyclic AMP concentration following addition of epinephrine was half that in control cells. Elevation of GTP concentrations above normal and had no effect on cyclic AMP concentrations following epinephrine treatment."}
{"id": "PMID:201683", "title": "Elevation of the cyclic GMP concentration in human platelets by sodium ascorbate and 5-hydroxytryptamine.", "content": "Sodium L-ascorbate (ascorbate) and sodium D-ascorbate produced a dose-related rise of guanosine 3':5'-cyclic monophosphate (cGMP) in platelets with a maximum increment averaging 25-fold at 5 mM ascorbate. The ascorbate-induced increment in cGMP reached a peak after 1 min and was maintained for 1 h in the presence of ascorbate. 5-hydroxytryptamine (5-HT) also produced a dose-related rise of cGMP in platelets with a peak effect of approximately 25-fold at 16 micrometer 5-HT. The elevation of cGMP in platelets by both ascorbate and 5-HT did not require extracellular calcium and was blocked by inhibitors of cyclo-oxygenase such as aspirin or indomethacin. A maximum ascorbate-induced rise in platelet cGMP at the time of addition of epinephrine, collage or thrombin did not augment the release of [14C]5-hydroxytryptamine ([14C]5-HT) measured over 30 min. Although ascorbate appeared to increase platelet cGMP by modulation of endoperoxide formation, its failure to aggregate platelets or to influence the release reaction indicates that the ascorbate-stimulated rise in cGMP does not have a simple relationship to thromboxane formation.", "contents": "Elevation of the cyclic GMP concentration in human platelets by sodium ascorbate and 5-hydroxytryptamine. Sodium L-ascorbate (ascorbate) and sodium D-ascorbate produced a dose-related rise of guanosine 3':5'-cyclic monophosphate (cGMP) in platelets with a maximum increment averaging 25-fold at 5 mM ascorbate. The ascorbate-induced increment in cGMP reached a peak after 1 min and was maintained for 1 h in the presence of ascorbate. 5-hydroxytryptamine (5-HT) also produced a dose-related rise of cGMP in platelets with a peak effect of approximately 25-fold at 16 micrometer 5-HT. The elevation of cGMP in platelets by both ascorbate and 5-HT did not require extracellular calcium and was blocked by inhibitors of cyclo-oxygenase such as aspirin or indomethacin. A maximum ascorbate-induced rise in platelet cGMP at the time of addition of epinephrine, collage or thrombin did not augment the release of [14C]5-hydroxytryptamine ([14C]5-HT) measured over 30 min. Although ascorbate appeared to increase platelet cGMP by modulation of endoperoxide formation, its failure to aggregate platelets or to influence the release reaction indicates that the ascorbate-stimulated rise in cGMP does not have a simple relationship to thromboxane formation."}
{"id": "PMID:201684", "title": "Regional levels of cyclic AMP in rat brain: pitfalls of microwave inactivation.", "content": "Techniques of in-vivo microwave irradiation to inactivate brain enzymes in rats were varied as to exposure configuration and output power. The rate at which metabolism was stopped was studied in various regions of the rat brain, using changes in levels of cyclic AMP and phosphodiesterase activity. Exposure times required to obtain stabilized levels of cyclic AMP varied in different brain regions, i.e., hypothalamus, cortex and cerebellum. Levels of cyclic AMP in selective regions of the brain decreased as more rapid inactivation was achieved. The authors identify important sources of variability of present microwave inactivation systems and the need for improved control of signficant microwave parameters.", "contents": "Regional levels of cyclic AMP in rat brain: pitfalls of microwave inactivation. Techniques of in-vivo microwave irradiation to inactivate brain enzymes in rats were varied as to exposure configuration and output power. The rate at which metabolism was stopped was studied in various regions of the rat brain, using changes in levels of cyclic AMP and phosphodiesterase activity. Exposure times required to obtain stabilized levels of cyclic AMP varied in different brain regions, i.e., hypothalamus, cortex and cerebellum. Levels of cyclic AMP in selective regions of the brain decreased as more rapid inactivation was achieved. The authors identify important sources of variability of present microwave inactivation systems and the need for improved control of signficant microwave parameters."}
{"id": "PMID:201685", "title": "Dermatofibrosarcoma protuberans.", "content": "Dermatofibrosarcoma protuberans is a well-differentiated sarcoma that rarely metastasizes but is characterized by a high recurrence rate. This is due to clinically undetectable, microscopic extensions into the surrounding dermis. Chemosurgery (Mohs) is effective in the ablation of this tumor because the extensions can be identified and eradicated.", "contents": "Dermatofibrosarcoma protuberans. Dermatofibrosarcoma protuberans is a well-differentiated sarcoma that rarely metastasizes but is characterized by a high recurrence rate. This is due to clinically undetectable, microscopic extensions into the surrounding dermis. Chemosurgery (Mohs) is effective in the ablation of this tumor because the extensions can be identified and eradicated."}
{"id": "PMID:201687", "title": "Comparative psychologic effects of estrogen administration on institutional and noninstitutional elderly women.", "content": "Previous research on elderly women living in institutions has showm a postiive relationship between the administration of estrogen and improved psychologic status. In the current 12-month study, the effects of estrogen therapy were compared in 18 institutional women versus 21 noninstitutional women who volunteered to participate. Both groups received conjugated estrogens (Premarin, 0.3 mg daily) in interrupted courses. Throughout the year, the women were evaluated by means of the Eysenck Personality Inventory, the Profile of Mood States, the Lawson Morale Scale, and various self-perception items. Statistically, significant changes occurred in the areas of neuroticism, tension, morale, and subjective mood states, but the improvement was greater in the institutional subjects. The main conclusion was that estrogen therapy has a positive effect upon psychologic status, particularly for women who reside in an institution.", "contents": "Comparative psychologic effects of estrogen administration on institutional and noninstitutional elderly women. Previous research on elderly women living in institutions has showm a postiive relationship between the administration of estrogen and improved psychologic status. In the current 12-month study, the effects of estrogen therapy were compared in 18 institutional women versus 21 noninstitutional women who volunteered to participate. Both groups received conjugated estrogens (Premarin, 0.3 mg daily) in interrupted courses. Throughout the year, the women were evaluated by means of the Eysenck Personality Inventory, the Profile of Mood States, the Lawson Morale Scale, and various self-perception items. Statistically, significant changes occurred in the areas of neuroticism, tension, morale, and subjective mood states, but the improvement was greater in the institutional subjects. The main conclusion was that estrogen therapy has a positive effect upon psychologic status, particularly for women who reside in an institution."}
{"id": "PMID:201698", "title": "Two-step separation of human peripheral blood monocytes on discontinuous density gradients of colloidal silica-polyvinylpyrrolidinone.", "content": "Normal human peripheral blood monocytes were purified by a two-step separation. The first step, the standard Ficoll--Hypaque (F--H) buoyant density centrifugation, yielded mainly mononuclear cells, of which 24 +/- 9% were monocytes. Isopycnic centrifugation on discontinuous gradients of colloidal silica polyvinylpyrrolidinone (CS-PVP) further separated these mononuclear cells. The density interface between 1.070 and 1.060 g/ml yielded 82 +/- 7% monocytes, 5 +/- 4% granulocytes and 13 +/- 8% lymphocytes. Sixty-six percent of the monocytes obtained after F--H separation were recovered in this layer. The monocytes were intact and viable and retained their ability to phagocytose and kill Candida pseudotropicalis and to spread on glass coverslips. Motility (both random and towards a chemoattractant) was retained but was quantitatively less than after F--H separation alone. The relative purity of the monocyte population allowed assessment of major histocompatibility surface antigens by serotyping. This confirmed the presence of HLA and Ia-like antigens on monocytes.", "contents": "Two-step separation of human peripheral blood monocytes on discontinuous density gradients of colloidal silica-polyvinylpyrrolidinone. Normal human peripheral blood monocytes were purified by a two-step separation. The first step, the standard Ficoll--Hypaque (F--H) buoyant density centrifugation, yielded mainly mononuclear cells, of which 24 +/- 9% were monocytes. Isopycnic centrifugation on discontinuous gradients of colloidal silica polyvinylpyrrolidinone (CS-PVP) further separated these mononuclear cells. The density interface between 1.070 and 1.060 g/ml yielded 82 +/- 7% monocytes, 5 +/- 4% granulocytes and 13 +/- 8% lymphocytes. Sixty-six percent of the monocytes obtained after F--H separation were recovered in this layer. The monocytes were intact and viable and retained their ability to phagocytose and kill Candida pseudotropicalis and to spread on glass coverslips. Motility (both random and towards a chemoattractant) was retained but was quantitatively less than after F--H separation alone. The relative purity of the monocyte population allowed assessment of major histocompatibility surface antigens by serotyping. This confirmed the presence of HLA and Ia-like antigens on monocytes."}
{"id": "PMID:201699", "title": "Oxidative phosphorylation in rat oral mucosal mitochondria.", "content": "Oral mucosal mitochondria were isolated and characterized morphologically by electron microscopy. Polarographic measurements were made of respiration and oxidative phosphorylation in the mitochondrial preparations. ADP:O ratios approaching or slightly exceeding the theoretical maxima and stabilized respiratory control ratios were achieved with malate + glutamate, succinate and ascorbate-N,N,N1N1 tetramethyl-p-phenylenediamine (TMPD) as substrates. Inhibition by rotenone, antimycin A, azide, and cyanide established the classical electron transport chain as the major pathway of mitochondrial respiration. Respiration of the oral mucosal mitochondria was stimulated by DNP in the presence of succinate. DNP-stimulated respiration exceeded that observed in the presence of ADP plus Pi and increasing the concentration of DNP progressively inhibited respiration.", "contents": "Oxidative phosphorylation in rat oral mucosal mitochondria. Oral mucosal mitochondria were isolated and characterized morphologically by electron microscopy. Polarographic measurements were made of respiration and oxidative phosphorylation in the mitochondrial preparations. ADP:O ratios approaching or slightly exceeding the theoretical maxima and stabilized respiratory control ratios were achieved with malate + glutamate, succinate and ascorbate-N,N,N1N1 tetramethyl-p-phenylenediamine (TMPD) as substrates. Inhibition by rotenone, antimycin A, azide, and cyanide established the classical electron transport chain as the major pathway of mitochondrial respiration. Respiration of the oral mucosal mitochondria was stimulated by DNP in the presence of succinate. DNP-stimulated respiration exceeded that observed in the presence of ADP plus Pi and increasing the concentration of DNP progressively inhibited respiration."}
{"id": "PMID:201701", "title": "Activation of the kallikrein system in hyperbetalipoproteinemia.", "content": "In 30 patients with hyperlipoproteinemia (19 type II and 11 type IV), the role of the intrinsic coagulation pathway was evaluated by assays of preK, Kl's, and Hageman factor (factor XII). Analysis of the plasma of type II patients suggested activation of the intrinsic pathway characterized by a 40% decrease in preK (p less than 0.01) and a 50% decrease Kl (p less than 0.01); in contrast, analysis of the plasma of type IV patients showed no activation of the intrinsic pathway. In type II patients C-1INH was present in normal concentrations as measured by immunochemical techniques. The findings of normal levels of C-1INH by immunoassay, in association with altered electrophoretic mobility, are suggestive of formation of a kallikrein-C-1INH complex in vivo.", "contents": "Activation of the kallikrein system in hyperbetalipoproteinemia. In 30 patients with hyperlipoproteinemia (19 type II and 11 type IV), the role of the intrinsic coagulation pathway was evaluated by assays of preK, Kl's, and Hageman factor (factor XII). Analysis of the plasma of type II patients suggested activation of the intrinsic pathway characterized by a 40% decrease in preK (p less than 0.01) and a 50% decrease Kl (p less than 0.01); in contrast, analysis of the plasma of type IV patients showed no activation of the intrinsic pathway. In type II patients C-1INH was present in normal concentrations as measured by immunochemical techniques. The findings of normal levels of C-1INH by immunoassay, in association with altered electrophoretic mobility, are suggestive of formation of a kallikrein-C-1INH complex in vivo."}
{"id": "PMID:201702", "title": "Some ultrastructural features of acinic cell carcinoma.", "content": "The ultrastructure of an acinic cell carcinoma, occurring in the left parotid gland of a 52-year-old woman and causing a total facial nerve paralysis, is described. Histologically the tumour consisted of numerous granulated cells arranged around lumen-like openings and resembling a secretory system. Furthermore, areas with agranulated cells growing in a solid pattern were also encountered. In the electron microscope the cytoplasmic granules of the tumour cells displayed a varied appearance. Granules of a dense homogeneous type, as well as granules with a more electron lucid appearance were observed. Furthermore, numerous cytoplasmic granules displayed a bipartite structure with a dense central and a more electron lucid outer zone. In specimens primarily fixed in OSO4 or KMnO4 the granules displayed a 'leached out' appearance. The membrane-bounded of the tumour cells also showed a strong positive staining with the periodic acid-chromic silver technique of Rambourg et al. (1969). Other characteristic ultrastructural features of the tumour cells studied were: Smooth cell surfaces, the presence of subplasmalemmal bands of electron dense material, desmosome-like attachment areas between cells and grossly altered mitochondria.", "contents": "Some ultrastructural features of acinic cell carcinoma. The ultrastructure of an acinic cell carcinoma, occurring in the left parotid gland of a 52-year-old woman and causing a total facial nerve paralysis, is described. Histologically the tumour consisted of numerous granulated cells arranged around lumen-like openings and resembling a secretory system. Furthermore, areas with agranulated cells growing in a solid pattern were also encountered. In the electron microscope the cytoplasmic granules of the tumour cells displayed a varied appearance. Granules of a dense homogeneous type, as well as granules with a more electron lucid appearance were observed. Furthermore, numerous cytoplasmic granules displayed a bipartite structure with a dense central and a more electron lucid outer zone. In specimens primarily fixed in OSO4 or KMnO4 the granules displayed a 'leached out' appearance. The membrane-bounded of the tumour cells also showed a strong positive staining with the periodic acid-chromic silver technique of Rambourg et al. (1969). Other characteristic ultrastructural features of the tumour cells studied were: Smooth cell surfaces, the presence of subplasmalemmal bands of electron dense material, desmosome-like attachment areas between cells and grossly altered mitochondria."}
{"id": "PMID:201705", "title": "Action of anthocyanosides of Vaccinium myrtillis on the permeability of the blood brain barrier.", "content": "Proteases and especially collagenase injected into the lateral brain ventricles of rats are able to increase the permeability of the blood-brain barrier to trypan blue. Treatment of the rats with anthocyanosides of Vaccinium myrtillis diminishes the permeability increasing effect of collagenase and accelerate the recovery of normal permeability. This effect seems to be related to a less effective enzymatic attack on collagen, as hydroxyproline content in the CSF is increased less after collagenase injection in treated animals than in untreated controls.", "contents": "Action of anthocyanosides of Vaccinium myrtillis on the permeability of the blood brain barrier. Proteases and especially collagenase injected into the lateral brain ventricles of rats are able to increase the permeability of the blood-brain barrier to trypan blue. Treatment of the rats with anthocyanosides of Vaccinium myrtillis diminishes the permeability increasing effect of collagenase and accelerate the recovery of normal permeability. This effect seems to be related to a less effective enzymatic attack on collagen, as hydroxyproline content in the CSF is increased less after collagenase injection in treated animals than in untreated controls."}
{"id": "PMID:201707", "title": "Autoradiographic localization of the binding of 125I-labelled prolactin to rat tissues in vitro.", "content": "The binding of 125I-labelled prolactin to normal rat tissues was examined with autoradiographic techniques. Tissue slices were incubated with 125I-labelled ovine prolactin in the presence or absence of excess unlabelled hormone to distinguish between the specific and the non-specific localization of grains. Specific binding was found in the liver, adrenal gland and kidney from female rats, and in the mammary gland, ovary, testis and prostate gland. Conversely, fat, muscle, heart, lung, and spleen from female rats and uterine tissue did not bind 125I-labelled prolactin appreciably, or show competition for binding in the presence of unlabelled hormone. In the testis, prolactin bound exclusively to Leydig cells; in the prostate gland, binding was localized in the secretory epithelium. Kidney tubules in the cortex displayed specific prolactin localization whereas the medulla did not bind prolactin. Adrenal medulla showed no hormone binding; however, the zona reticularis and to a lesser extent the zona fasciculata bound prolactin. In the ovary, grains were limited to the theca and to a lesser extent the corpus luteum and follicles. In all cases, binding was essentially abolished when unlabelled prolactin was included in the incubation medium. These results confirm reports of the presence of prolactin receptors in these tissues and serve to identify the cells within a particular organ that respond to prolactin.", "contents": "Autoradiographic localization of the binding of 125I-labelled prolactin to rat tissues in vitro. The binding of 125I-labelled prolactin to normal rat tissues was examined with autoradiographic techniques. Tissue slices were incubated with 125I-labelled ovine prolactin in the presence or absence of excess unlabelled hormone to distinguish between the specific and the non-specific localization of grains. Specific binding was found in the liver, adrenal gland and kidney from female rats, and in the mammary gland, ovary, testis and prostate gland. Conversely, fat, muscle, heart, lung, and spleen from female rats and uterine tissue did not bind 125I-labelled prolactin appreciably, or show competition for binding in the presence of unlabelled hormone. In the testis, prolactin bound exclusively to Leydig cells; in the prostate gland, binding was localized in the secretory epithelium. Kidney tubules in the cortex displayed specific prolactin localization whereas the medulla did not bind prolactin. Adrenal medulla showed no hormone binding; however, the zona reticularis and to a lesser extent the zona fasciculata bound prolactin. In the ovary, grains were limited to the theca and to a lesser extent the corpus luteum and follicles. In all cases, binding was essentially abolished when unlabelled prolactin was included in the incubation medium. These results confirm reports of the presence of prolactin receptors in these tissues and serve to identify the cells within a particular organ that respond to prolactin."}
{"id": "PMID:201708", "title": "Metabolic effects of cortisol, corticosterone and adrenocorticotrophin in a prototherian mammal Tachyglossus aculeatus (Shaw).", "content": "The effects of injections of cortisol, corticosterone and ACTH on indices of carbohydrate, fat and protein metabolism were investigated in the conscious echidna, Tachyglossus aculeatus. Intravenous infusion of cortisol and corticosterone for 2 h at rates of 3 and 30 microgram/kg/h respectively did not cause significant changes in the plasma concentrations of glucose, urea or amino acids during a 12.5 h observation period. In contrast, a dose-related increase in plasma free fatty acid (FFA) concentration was observed. Infusion of synthetic ACTH at 2 i.u./kg/h for 2 h caused a minor, short-lived increase in FFA concentration. Daily i.m. injections of 0.2 mg cortisol or corticosterone acetates/kg, which raised plasma total corticosteroid concentrations to levels characteristic of maximal ACTH stimulation, did not cause glycosuria nor was there any change in body weight, nitrogen intake or urinary nitrogen excretion. However, there was a minor, but significant, increase in plasma glucose concentration. The liver glycogen content of 24 h fasted, corticosteroid-treated animals was similar to that of fasted control animals. It is concluded that cortisol, corticosterone and ACTH have only minor effects on carbohydrate and protein metabolism and that the main action of these hormones may be to mobilize fat reserves.", "contents": "Metabolic effects of cortisol, corticosterone and adrenocorticotrophin in a prototherian mammal Tachyglossus aculeatus (Shaw). The effects of injections of cortisol, corticosterone and ACTH on indices of carbohydrate, fat and protein metabolism were investigated in the conscious echidna, Tachyglossus aculeatus. Intravenous infusion of cortisol and corticosterone for 2 h at rates of 3 and 30 microgram/kg/h respectively did not cause significant changes in the plasma concentrations of glucose, urea or amino acids during a 12.5 h observation period. In contrast, a dose-related increase in plasma free fatty acid (FFA) concentration was observed. Infusion of synthetic ACTH at 2 i.u./kg/h for 2 h caused a minor, short-lived increase in FFA concentration. Daily i.m. injections of 0.2 mg cortisol or corticosterone acetates/kg, which raised plasma total corticosteroid concentrations to levels characteristic of maximal ACTH stimulation, did not cause glycosuria nor was there any change in body weight, nitrogen intake or urinary nitrogen excretion. However, there was a minor, but significant, increase in plasma glucose concentration. The liver glycogen content of 24 h fasted, corticosteroid-treated animals was similar to that of fasted control animals. It is concluded that cortisol, corticosterone and ACTH have only minor effects on carbohydrate and protein metabolism and that the main action of these hormones may be to mobilize fat reserves."}
{"id": "PMID:201709", "title": "Stimulation of prostaglandin accumulation in the rat anterior pituitary gland by luteinizing hormone releasing hormone in vitro.", "content": "The addition of luteinizing hormone releasing hormone releasing hormone (LH-RH) to cultures of monolayers of rat anterior pituitary cells was shown to increase both the concentrations of prostaglandins E1 and E2 (PGE) in the cells and the release of LH over similar ranges of concentrations of LH-RH (10(-6) to 10(-10) mol/l). The peak concentration of PGE was observed after 2.5 h. The stimulation of the level of PGE in the cells by LH-RH was completely inhibited by two inhibitors of prostaglandin synthetase, which only partially inhibited the stimulation of LH release. Therefore the increased concentration of PGE was not obligatory for the effect of LH-RH on LH release. It was also shown that monobutyryl cyclic AMP stimulated the intracellular concentration of PGE and it is suggested that the stimulation of PGE levels may be mediated by increased levels of cyclic AMP in the cells after the addition of LH-RH.", "contents": "Stimulation of prostaglandin accumulation in the rat anterior pituitary gland by luteinizing hormone releasing hormone in vitro. The addition of luteinizing hormone releasing hormone releasing hormone (LH-RH) to cultures of monolayers of rat anterior pituitary cells was shown to increase both the concentrations of prostaglandins E1 and E2 (PGE) in the cells and the release of LH over similar ranges of concentrations of LH-RH (10(-6) to 10(-10) mol/l). The peak concentration of PGE was observed after 2.5 h. The stimulation of the level of PGE in the cells by LH-RH was completely inhibited by two inhibitors of prostaglandin synthetase, which only partially inhibited the stimulation of LH release. Therefore the increased concentration of PGE was not obligatory for the effect of LH-RH on LH release. It was also shown that monobutyryl cyclic AMP stimulated the intracellular concentration of PGE and it is suggested that the stimulation of PGE levels may be mediated by increased levels of cyclic AMP in the cells after the addition of LH-RH."}
{"id": "PMID:201710", "title": "Distribution of corticotrophin releasing factor activity within the hypothalamic-pituitary complex of rats and cattle.", "content": "An assay system involving cultured rat adenohypophysial cells from either intact or adrenalectomized donors was used to study the distribution of corticotrophin releasing factor (CRF) activity in the hypothalamic-pituitary complex of rats and cattle. In the rat hypothalamus, CRF activity was most concentrated in the median eminence, but CRF was present in the stalk and the posterior pituitary gland in much higher concentrations than in the median eminence in both species. The dose--response slopes for the median eminence, stalk and pars nervosa of the posterior pituitary gland were parallel to each other, suggesting a qualitative similarity between the CRF activity in these tissues. Rat posterior pituitary glands may also contain another CRF component which has a much flatter dose--response curve, but is detectable in smaller quantities of posterior pituitary tissue than is the other type of CRF.", "contents": "Distribution of corticotrophin releasing factor activity within the hypothalamic-pituitary complex of rats and cattle. An assay system involving cultured rat adenohypophysial cells from either intact or adrenalectomized donors was used to study the distribution of corticotrophin releasing factor (CRF) activity in the hypothalamic-pituitary complex of rats and cattle. In the rat hypothalamus, CRF activity was most concentrated in the median eminence, but CRF was present in the stalk and the posterior pituitary gland in much higher concentrations than in the median eminence in both species. The dose--response slopes for the median eminence, stalk and pars nervosa of the posterior pituitary gland were parallel to each other, suggesting a qualitative similarity between the CRF activity in these tissues. Rat posterior pituitary glands may also contain another CRF component which has a much flatter dose--response curve, but is detectable in smaller quantities of posterior pituitary tissue than is the other type of CRF."}
{"id": "PMID:201718", "title": "Interaction of thyrotrophin with the human thyrotrophin receptor.", "content": "The relationship between the binding of thyrotrophin (TSH) to receptors and the production of cyclic AMP has been investigated using crude human thyroid membranes. Receptor binding was studied by use of 125I-labelled bovine TSH, which had been purified by adsorption to and elution from human thyroid membranes. This 125I-labelled material showed the same biological activity as the unlabelled hormone. Binding studies at equilibrium indicated that the association constant of the TSH-membrane interaction decreased as the amount of TSH bound increased. Kinetic data did not provide definite evidence that this was due to an effect of increasing receptor occupancy on the dissociation rate constant. Detectable stimulation by TSH of cyclic AMP production by the membranes was observed with as little as 30 micromicron. (1 ng) hormone. Increasing amounts of TSH over the range 0-250 micromicron caused increases in the production of cyclic AMP, proportional to the amount of hormone bound. With larger amounts of TSH, increasingly greater amounts of bound hormone were required to give corresponding increases in cyclic AMP formation, and addition of TSH in amounts greater than 16 millimicron resulted in progressive inhibition of cyclic AMP formation. Kinetic studies indicated that receptor binding was not rate-limiting in the stimulation of cyclic AMP production by TSH.", "contents": "Interaction of thyrotrophin with the human thyrotrophin receptor. The relationship between the binding of thyrotrophin (TSH) to receptors and the production of cyclic AMP has been investigated using crude human thyroid membranes. Receptor binding was studied by use of 125I-labelled bovine TSH, which had been purified by adsorption to and elution from human thyroid membranes. This 125I-labelled material showed the same biological activity as the unlabelled hormone. Binding studies at equilibrium indicated that the association constant of the TSH-membrane interaction decreased as the amount of TSH bound increased. Kinetic data did not provide definite evidence that this was due to an effect of increasing receptor occupancy on the dissociation rate constant. Detectable stimulation by TSH of cyclic AMP production by the membranes was observed with as little as 30 micromicron. (1 ng) hormone. Increasing amounts of TSH over the range 0-250 micromicron caused increases in the production of cyclic AMP, proportional to the amount of hormone bound. With larger amounts of TSH, increasingly greater amounts of bound hormone were required to give corresponding increases in cyclic AMP formation, and addition of TSH in amounts greater than 16 millimicron resulted in progressive inhibition of cyclic AMP formation. Kinetic studies indicated that receptor binding was not rate-limiting in the stimulation of cyclic AMP production by TSH."}
{"id": "PMID:201719", "title": "Interaction of thyroid-stimulating antibodies with the human thyrotrophin receptor.", "content": "Thyroid-stimulating antibodies (TSAb) were found to inhibit the binding of labelled thyrotrophin (TSH) to thyroid membranes in a dose-dependent manner and this effect was localized in the Fab part of the TSAb molecule. Analysis of the binding data suggested that TSAb and TSH bound to the same receptor site. Production of cyclic AMP by the thyroid membranes was stimulated by TSAb and TSAb-Fab with a similar time course to that observed with TSH. Kinetic studies indicated that the binding of TSAb to the thyroid membranes was not rate-limiting in the process of stimulation of cyclic AMP production.", "contents": "Interaction of thyroid-stimulating antibodies with the human thyrotrophin receptor. Thyroid-stimulating antibodies (TSAb) were found to inhibit the binding of labelled thyrotrophin (TSH) to thyroid membranes in a dose-dependent manner and this effect was localized in the Fab part of the TSAb molecule. Analysis of the binding data suggested that TSAb and TSH bound to the same receptor site. Production of cyclic AMP by the thyroid membranes was stimulated by TSAb and TSAb-Fab with a similar time course to that observed with TSH. Kinetic studies indicated that the binding of TSAb to the thyroid membranes was not rate-limiting in the process of stimulation of cyclic AMP production."}
{"id": "PMID:201723", "title": "Effects of low-chloride solutions on action potentials of sheep cardiac Purkinje fibers.", "content": "The rapid repolarization during phase 1 of the action potential of sheep cardiac purkinje fibers has been attributed to a time- and voltage-dependent chloride current. In part, this conclusion was based on experiments that showed a substantial slowing of phase 1 when larger, presumably impermeant, anions were substituted for chloride in tyrode's solution. We have re- examined the electrical effects of low-chloride solutions. We recorded action potentials of sheep cardiac purkinje fibers in normal tyrode's solution and in low-chloride solutions made by substituting sodium propionate, acetylglycinate, methylsulfate, or methanesulfonate for the NaCl of Tyrode's solution. Total calcium was adjusted to keep calcium ion activity of test solutions equal to that of control solutions. Propionate gave qualitatively variable results in preliminary experiments; it was not tested further. Low-chloride solutions made with the other anions gave much more consistent results: phase 1 and the notch that often occurs between phases 1 and 2 were usually unaffected, and the action potential duration usually increased. The only apparent change in the resting potential was a transient 3-6 mV depolarization when low-chloride solution was first admitted to the chamber, and a symmetrical transient hyperpolarization when chloride was returned to normal. If a time- and voltage-dependent chloride current exists in sheep cardiac purkinje fibers, our results suggest that it plays little role in generating phase 1 of the action potential.", "contents": "Effects of low-chloride solutions on action potentials of sheep cardiac Purkinje fibers. The rapid repolarization during phase 1 of the action potential of sheep cardiac purkinje fibers has been attributed to a time- and voltage-dependent chloride current. In part, this conclusion was based on experiments that showed a substantial slowing of phase 1 when larger, presumably impermeant, anions were substituted for chloride in tyrode's solution. We have re- examined the electrical effects of low-chloride solutions. We recorded action potentials of sheep cardiac purkinje fibers in normal tyrode's solution and in low-chloride solutions made by substituting sodium propionate, acetylglycinate, methylsulfate, or methanesulfonate for the NaCl of Tyrode's solution. Total calcium was adjusted to keep calcium ion activity of test solutions equal to that of control solutions. Propionate gave qualitatively variable results in preliminary experiments; it was not tested further. Low-chloride solutions made with the other anions gave much more consistent results: phase 1 and the notch that often occurs between phases 1 and 2 were usually unaffected, and the action potential duration usually increased. The only apparent change in the resting potential was a transient 3-6 mV depolarization when low-chloride solution was first admitted to the chamber, and a symmetrical transient hyperpolarization when chloride was returned to normal. If a time- and voltage-dependent chloride current exists in sheep cardiac purkinje fibers, our results suggest that it plays little role in generating phase 1 of the action potential."}
{"id": "PMID:201724", "title": "Electrical and adaptive properties of rod photoreceptors in Bufo marinus. II. Effects of cyclic nucleotides and prostaglandins.", "content": "Substances known to alter cyclic nucleotide levels in cells were applied to the isolated toad retina and effects on rod electrical and adaptive behavior were studied. The retina was continually superfused in control ringer's or ringer's containing one or a combination of drugs, and rod activity was recorded intracellularly. Superfusion with cGMP, Bu(2)GMP, isobutylmethylxanthine (IBMX; a phosphodiesterase inhibitor), or PGF(2alpha) (a prostaglandin) caused effects in rods that closely match those observed when extracellular Ca(2+) levels were lowered. For example, short exposures (up to 6 min) of the retina to these substances caused depolarization of the membrane potential, increase in response amplitudes, and some changes in waveform; but under dark-adapted or partially light-adapted conditions receptor sensitivity was virtually unaffected. That is, the position of the V-log I curve on the intensity axis was determined by the prevailing light level, not by drug level. These drugs, like lowered extracellular Ca(2+), also decreased the period of receptor saturation after a bright-adapting flash, resulting in an acceleration of the onset of membrane and sensitivity recovery during dark adaptation. Long-term (6-15 min) exposure of a dark-adapted retina to 5 mM IBMX or a combination of IBMX and cGMP caused a loss of response amplitude and a desensitization of the rods that was similar to that observed in rods after a long-term low Ca(2+) (10(-9)M) treatment. Application of high (3.2 mM) Ca(2+) to the retina blocked the effects of applied Bu(2)cGMP. PGE(1) superfusion mimicked the effects of increasing extracellular Ca(2+). The results show that increased cGMP and lowered Ca(2+) produce similar alterations in the electrical activity of rods. These findings suggest that Ca(2+) and cGMP are interrelated messengers. We speculate that low Ca(2+) may lead to increased intracellular cGMP, and/or that applied cGMP, and/or that applied cGMP may lower cytosol Ca(2+), perhaps by stimulating Ca(2+)- ATPase pumps in the outer segment.", "contents": "Electrical and adaptive properties of rod photoreceptors in Bufo marinus. II. Effects of cyclic nucleotides and prostaglandins. Substances known to alter cyclic nucleotide levels in cells were applied to the isolated toad retina and effects on rod electrical and adaptive behavior were studied. The retina was continually superfused in control ringer's or ringer's containing one or a combination of drugs, and rod activity was recorded intracellularly. Superfusion with cGMP, Bu(2)GMP, isobutylmethylxanthine (IBMX; a phosphodiesterase inhibitor), or PGF(2alpha) (a prostaglandin) caused effects in rods that closely match those observed when extracellular Ca(2+) levels were lowered. For example, short exposures (up to 6 min) of the retina to these substances caused depolarization of the membrane potential, increase in response amplitudes, and some changes in waveform; but under dark-adapted or partially light-adapted conditions receptor sensitivity was virtually unaffected. That is, the position of the V-log I curve on the intensity axis was determined by the prevailing light level, not by drug level. These drugs, like lowered extracellular Ca(2+), also decreased the period of receptor saturation after a bright-adapting flash, resulting in an acceleration of the onset of membrane and sensitivity recovery during dark adaptation. Long-term (6-15 min) exposure of a dark-adapted retina to 5 mM IBMX or a combination of IBMX and cGMP caused a loss of response amplitude and a desensitization of the rods that was similar to that observed in rods after a long-term low Ca(2+) (10(-9)M) treatment. Application of high (3.2 mM) Ca(2+) to the retina blocked the effects of applied Bu(2)cGMP. PGE(1) superfusion mimicked the effects of increasing extracellular Ca(2+). The results show that increased cGMP and lowered Ca(2+) produce similar alterations in the electrical activity of rods. These findings suggest that Ca(2+) and cGMP are interrelated messengers. We speculate that low Ca(2+) may lead to increased intracellular cGMP, and/or that applied cGMP, and/or that applied cGMP may lower cytosol Ca(2+), perhaps by stimulating Ca(2+)- ATPase pumps in the outer segment."}
{"id": "PMID:201725", "title": "Regulation of synthesis of benzyl alcohol dehydrogenase in Acinetobacter calcoaceticus NCIB8250.", "content": "Specific activity of benzyl alcohol dehydrogenase in carbon-limited continuous cultures was at a maximum at a specific growth rate of 0.2 h-1, but fell off at lower and higher growth rates. The specific activity in nitrogen-limited cultures was always lower and was inversely proportional to growth rate. There was severe repression of benzyl alcohol dehydrogenase during metabolism of L(+)-mandelate or phenylglyoxylate in batch cultures. Synthesis of benzyl alcohol dehydrogenase was followed in experiments where various compounds, including a gratuitous inducer and an anti-inducer of the mandelate enzymes, were added to uninduced or pre-induced cultures and to constitutive and blocked mutants. The results led to the conclusion that there were at least two types of repression. One was caused by phenylglyoxylate carbon-lyase (or a compound synthesized co-ordinately with it), but not by the other mandelate enzymes or by L(+)-mandelate, phenylglyoxylate, benzaldehyde or benzoate. A second type of repression was observed during rapid growth or after the addition of compound such as succinate which are rapidly and completely metabolized.", "contents": "Regulation of synthesis of benzyl alcohol dehydrogenase in Acinetobacter calcoaceticus NCIB8250. Specific activity of benzyl alcohol dehydrogenase in carbon-limited continuous cultures was at a maximum at a specific growth rate of 0.2 h-1, but fell off at lower and higher growth rates. The specific activity in nitrogen-limited cultures was always lower and was inversely proportional to growth rate. There was severe repression of benzyl alcohol dehydrogenase during metabolism of L(+)-mandelate or phenylglyoxylate in batch cultures. Synthesis of benzyl alcohol dehydrogenase was followed in experiments where various compounds, including a gratuitous inducer and an anti-inducer of the mandelate enzymes, were added to uninduced or pre-induced cultures and to constitutive and blocked mutants. The results led to the conclusion that there were at least two types of repression. One was caused by phenylglyoxylate carbon-lyase (or a compound synthesized co-ordinately with it), but not by the other mandelate enzymes or by L(+)-mandelate, phenylglyoxylate, benzaldehyde or benzoate. A second type of repression was observed during rapid growth or after the addition of compound such as succinate which are rapidly and completely metabolized."}
{"id": "PMID:201726", "title": "Increased numbers of heat-resistnat spores produced by two strains of Clostridium perfringens bearing temperate phage s9.", "content": "Sporulation kinetics and spore heat resistance data were compared for a lysogenic strain of Clostridium perfringens, s9, before and after curing with ultraviolet irradiation. The cured strain showed the same growth rate in broth media as the lysogenic strain but took 6 h longer to form refractile spores. For lysogenized and cured strains the percentages of refractile spores produced that were heat-resistant (80 degrees C for 15 min) were 50 and 0.2, respectively. When reinfected with the temperature phage, the cured strain produced spores in 2 to 3 h, like the original lysogenic culture, and 10% of the spores produced were heat-resistnat.", "contents": "Increased numbers of heat-resistnat spores produced by two strains of Clostridium perfringens bearing temperate phage s9. Sporulation kinetics and spore heat resistance data were compared for a lysogenic strain of Clostridium perfringens, s9, before and after curing with ultraviolet irradiation. The cured strain showed the same growth rate in broth media as the lysogenic strain but took 6 h longer to form refractile spores. For lysogenized and cured strains the percentages of refractile spores produced that were heat-resistant (80 degrees C for 15 min) were 50 and 0.2, respectively. When reinfected with the temperature phage, the cured strain produced spores in 2 to 3 h, like the original lysogenic culture, and 10% of the spores produced were heat-resistnat."}
{"id": "PMID:201727", "title": "Psychiatric follow-up studies. Practical procedures and ethical concerns.", "content": "The difficulties of performing prospective psychiatric follow-up studies have recently increased due to growing concern over the ethical issues involved. In a study to determine the efficacy of different lengths of psychiatric hospitalization 235 patients were followed for 2 years after study hospitalization. Data were obtained on more than 90 per cent of the patients. The cost of performing 100 follow-up interviews ranged from $9,169 for patients living within a 6-mile radius of the study site, to $17,942 for patients living within the contiguous United States. It is concluded that through persistent effort useful data can be obtained by follow-up of psychiatric patients, while maintaining ethical standards which include respect for the rights and wishes of the patient.", "contents": "Psychiatric follow-up studies. Practical procedures and ethical concerns. The difficulties of performing prospective psychiatric follow-up studies have recently increased due to growing concern over the ethical issues involved. In a study to determine the efficacy of different lengths of psychiatric hospitalization 235 patients were followed for 2 years after study hospitalization. Data were obtained on more than 90 per cent of the patients. The cost of performing 100 follow-up interviews ranged from $9,169 for patients living within a 6-mile radius of the study site, to $17,942 for patients living within the contiguous United States. It is concluded that through persistent effort useful data can be obtained by follow-up of psychiatric patients, while maintaining ethical standards which include respect for the rights and wishes of the patient."}
{"id": "PMID:201731", "title": "Therapeutic embolisation of the external carotid arterial tree.", "content": "Intra-arterial embolisation is a valuable adjunct to the treatment of many vascular lesions, including neoplasms such as glomus tumours or juvenile angiofibromas, and arteriovenous malformations. Its place in the management of the individual patient should be established before any surgical procedure is carried out, as this may prejudice the eventual result. The indications for the procedure, the technique, and possible complications are discussed in this paper, and it is emphasised that the latter are best avoided by the use of a scrupulous technique and adequate technical facilities.", "contents": "Therapeutic embolisation of the external carotid arterial tree. Intra-arterial embolisation is a valuable adjunct to the treatment of many vascular lesions, including neoplasms such as glomus tumours or juvenile angiofibromas, and arteriovenous malformations. Its place in the management of the individual patient should be established before any surgical procedure is carried out, as this may prejudice the eventual result. The indications for the procedure, the technique, and possible complications are discussed in this paper, and it is emphasised that the latter are best avoided by the use of a scrupulous technique and adequate technical facilities."}
{"id": "PMID:201732", "title": "Median--ulnar nerve communications and carpal tunnel syndrome.", "content": "Carpal tunnel syndrome in the presence of anomalous median to ulnar nerve communications in the forearm produces a characteristic change in motor conduction studies. Median nerve stimulation at the elbow evokes a thenar muscle action potential (MAP) with an initial positive deflection not seen on stimulation at the wrist. In 63 patients this change occurred in 16 (25%) and is a useful additional criterion in the diagnosis of carpal tunnel syndrome. The initial positive deflection is due to the volume-conducted MAP from the first dorsal interosseous and some thenar muscles whose motor point lies some distance from the recording electrode over abductor pollicis brevis. The first dorsal interosseous and thenar MAPs resulting from elbow stimulation of those median nerve axons crossing to ulnar nerve in forearm, are generated before that from thenar muscles supplied by the axons going through the carpal tunnel.", "contents": "Median--ulnar nerve communications and carpal tunnel syndrome. Carpal tunnel syndrome in the presence of anomalous median to ulnar nerve communications in the forearm produces a characteristic change in motor conduction studies. Median nerve stimulation at the elbow evokes a thenar muscle action potential (MAP) with an initial positive deflection not seen on stimulation at the wrist. In 63 patients this change occurred in 16 (25%) and is a useful additional criterion in the diagnosis of carpal tunnel syndrome. The initial positive deflection is due to the volume-conducted MAP from the first dorsal interosseous and some thenar muscles whose motor point lies some distance from the recording electrode over abductor pollicis brevis. The first dorsal interosseous and thenar MAPs resulting from elbow stimulation of those median nerve axons crossing to ulnar nerve in forearm, are generated before that from thenar muscles supplied by the axons going through the carpal tunnel."}
{"id": "PMID:201733", "title": "Sensory conduction in medial plantar nerve: normal values, clinical applications, and a comparison with the sural and upper limb sensory nerve action potentials in peripheral neuropathy.", "content": "A method for recording the medial plantar sensory nerve action potential at the ankle with surface electrodes is described. Normal values in 69 control subjects are given and compared with the sural sensory nerve action potential in the same limb in the same subjects. Clinical applications were studied in 33 patients. The procedure may be applied in the diagnosis of L4-5 nerve plexus or root lesions, lesions of the sciatic, posterior tibial, and medial plantar nerves, and is a more sensitive test than other sensory nerve action potentials in the diagnosis of peripheral neuropathy.", "contents": "Sensory conduction in medial plantar nerve: normal values, clinical applications, and a comparison with the sural and upper limb sensory nerve action potentials in peripheral neuropathy. A method for recording the medial plantar sensory nerve action potential at the ankle with surface electrodes is described. Normal values in 69 control subjects are given and compared with the sural sensory nerve action potential in the same limb in the same subjects. Clinical applications were studied in 33 patients. The procedure may be applied in the diagnosis of L4-5 nerve plexus or root lesions, lesions of the sciatic, posterior tibial, and medial plantar nerves, and is a more sensitive test than other sensory nerve action potentials in the diagnosis of peripheral neuropathy."}
{"id": "PMID:201734", "title": "Latent herpes simplex virus infection of mice. Infectious virus in homogenates of latently infected dorsal root ganglia.", "content": "C-57 albino weanling mice were latently infected with herpes simplex virus (Mp strain, type 1) by inoculation of 10(4) plaque forming units in the right hind footpad. The virus was demonstrable in explant cultures of the sacral dorsal root ganglia of these mice for as long as 18 months following inoculation. In addition, the virus was detectable when homogenates of these latently infected ganglia were placed on to differentiated organotypic cultures of fetal mouse dorsal root ganglia for as long as 8 months following inoculation of the mice. Virus was not demonstrable in these homogenates when they were placed on the Hela cells. The results suggest that during herpes simplex virus latent infection in mice there is continuous synthesis of infectious virus, probably in a highly localized area, which is detectable if a sensitive indicator substrate, such as these organotypic cultures, is used.", "contents": "Latent herpes simplex virus infection of mice. Infectious virus in homogenates of latently infected dorsal root ganglia. C-57 albino weanling mice were latently infected with herpes simplex virus (Mp strain, type 1) by inoculation of 10(4) plaque forming units in the right hind footpad. The virus was demonstrable in explant cultures of the sacral dorsal root ganglia of these mice for as long as 18 months following inoculation. In addition, the virus was detectable when homogenates of these latently infected ganglia were placed on to differentiated organotypic cultures of fetal mouse dorsal root ganglia for as long as 8 months following inoculation of the mice. Virus was not demonstrable in these homogenates when they were placed on the Hela cells. The results suggest that during herpes simplex virus latent infection in mice there is continuous synthesis of infectious virus, probably in a highly localized area, which is detectable if a sensitive indicator substrate, such as these organotypic cultures, is used."}
{"id": "PMID:201735", "title": "Changes of the neuronal endoplasmic reticulum in the peripheral nervous system in mutant hamsters with hind leg paralysis and normal controls.", "content": "The fine structure of the spinal root and gasserian ganglia of the mutant hamster with hind leg paralysis and of normal controls was examined. Three types of whorl-like or lamellar alteration of the endoplasmic reticulum were encountered but these were also found in the normal control animals and are therefore probably not related to the paralysis of the mutants. These alterations of the endoplasmic reticulum were similar to or identical with those seen in a variety of other conditions and in other types of cells. In the hamster, however the three configurations could sometimes be seen within the same membranous accumulations and are probably related to one another in a developmental fashion.", "contents": "Changes of the neuronal endoplasmic reticulum in the peripheral nervous system in mutant hamsters with hind leg paralysis and normal controls. The fine structure of the spinal root and gasserian ganglia of the mutant hamster with hind leg paralysis and of normal controls was examined. Three types of whorl-like or lamellar alteration of the endoplasmic reticulum were encountered but these were also found in the normal control animals and are therefore probably not related to the paralysis of the mutants. These alterations of the endoplasmic reticulum were similar to or identical with those seen in a variety of other conditions and in other types of cells. In the hamster, however the three configurations could sometimes be seen within the same membranous accumulations and are probably related to one another in a developmental fashion."}
{"id": "PMID:201736", "title": "Transsphenoidal microsurgical removal of 250 pituitary adenomas.", "content": "In a series of 250 pituitary adenomas, 72 (28.8%) were nonsecreting and 178 (71.2%) produced a hypersecretion syndrome: human growth hormone (83), prolactin (59), and adrenocorticotropic hormone (ACTH) (36). One-fifth had received prior treatment and one-fourth had visual impairment. The technical aspects of the transsphenoidal procedure are given with separate consideration of microadenomas and larger tumors. The results are provided in summary form with emphasis on the favorable outcome following removal of microadenomas. There was one postoperative death, and the complications observed after operation are presented.", "contents": "Transsphenoidal microsurgical removal of 250 pituitary adenomas. In a series of 250 pituitary adenomas, 72 (28.8%) were nonsecreting and 178 (71.2%) produced a hypersecretion syndrome: human growth hormone (83), prolactin (59), and adrenocorticotropic hormone (ACTH) (36). One-fifth had received prior treatment and one-fourth had visual impairment. The technical aspects of the transsphenoidal procedure are given with separate consideration of microadenomas and larger tumors. The results are provided in summary form with emphasis on the favorable outcome following removal of microadenomas. There was one postoperative death, and the complications observed after operation are presented."}
{"id": "PMID:201737", "title": "The ultrastructure of tubular carcinoma of the breast.", "content": "The ultrastructure of four tubular carcinomas of the breast is described. The neoplastic tubules are single layered and lack a myo-epithelial component, an important feature in distinguishing tubular carcinoma from sclerosing adenosis. Numerous myo-fibroblasts are present in the stroma of all four tumours and, since cells of this type have been recorded only occasionally in the stroma of other types of breast carcinoma, it is suggested that they may be a characteristic feature of tubular carcinomas.", "contents": "The ultrastructure of tubular carcinoma of the breast. The ultrastructure of four tubular carcinomas of the breast is described. The neoplastic tubules are single layered and lack a myo-epithelial component, an important feature in distinguishing tubular carcinoma from sclerosing adenosis. Numerous myo-fibroblasts are present in the stroma of all four tumours and, since cells of this type have been recorded only occasionally in the stroma of other types of breast carcinoma, it is suggested that they may be a characteristic feature of tubular carcinomas."}
{"id": "PMID:201738", "title": "Cyclic AMP and the mechanism of leucocyte lysosomal enzyme release during an immediate hypersensitivity reaction in vivo.", "content": "The pleural cavity of rats was used to study the effect of altering leucocyte cyclic AMP content on the release of B-glucuronidase activity during an immediate hypersensitivity reaction. The effect on intravenous colchicine was also studied. Despite an increase of 135 to 235% in leucocyte cyclic AMP content no decrease in B-glucuronidase release was observed. Similarly, colchicine had no effect on enzyme release. It was concluded that the cyclic nucleotides and leucocyte microtubules may have no significant role to play in the release of lysosomal enzymes during acute inflammation in vivo.", "contents": "Cyclic AMP and the mechanism of leucocyte lysosomal enzyme release during an immediate hypersensitivity reaction in vivo. The pleural cavity of rats was used to study the effect of altering leucocyte cyclic AMP content on the release of B-glucuronidase activity during an immediate hypersensitivity reaction. The effect on intravenous colchicine was also studied. Despite an increase of 135 to 235% in leucocyte cyclic AMP content no decrease in B-glucuronidase release was observed. Similarly, colchicine had no effect on enzyme release. It was concluded that the cyclic nucleotides and leucocyte microtubules may have no significant role to play in the release of lysosomal enzymes during acute inflammation in vivo."}
{"id": "PMID:201739", "title": "Tyrosinemia associated with perinatal infection with cytomegalovirus.", "content": "A premature infant presented with elevated concentrations of tyrosine in blood and urine, evidence of hepatocellular damage, demineralization of the bones, and a renal Fanconi syndrome. This is the clinical picture found in hereditary tyrosinemia. The infant also had a perinatal infection with cytomegalovirus.", "contents": "Tyrosinemia associated with perinatal infection with cytomegalovirus. A premature infant presented with elevated concentrations of tyrosine in blood and urine, evidence of hepatocellular damage, demineralization of the bones, and a renal Fanconi syndrome. This is the clinical picture found in hereditary tyrosinemia. The infant also had a perinatal infection with cytomegalovirus."}
{"id": "PMID:201740", "title": "Preoperative irradiation and chemotherapy for initially unresectable hepatoblastoma.", "content": "Three cases of hepatoblastoma that were deemed unresectable, both by angiographic study and exploration, became resectable following combined therapy of dactinomycin, vincristine, and irradiation.", "contents": "Preoperative irradiation and chemotherapy for initially unresectable hepatoblastoma. Three cases of hepatoblastoma that were deemed unresectable, both by angiographic study and exploration, became resectable following combined therapy of dactinomycin, vincristine, and irradiation."}
{"id": "PMID:201741", "title": "Computed tomographic scanning in children.", "content": "Computed tomographic scanning (CT) has been effectively utilized in evaluating the pediatric patient. Our experience with CT of the chest and abdomen in 19 patients has been described. The advantages offered by CT include: a unique anatomic display, the lack of morbidity, and an acceptable radiation dosage. Few technical disadvantages exist. Further application of this unique technique can be predicted.", "contents": "Computed tomographic scanning in children. Computed tomographic scanning (CT) has been effectively utilized in evaluating the pediatric patient. Our experience with CT of the chest and abdomen in 19 patients has been described. The advantages offered by CT include: a unique anatomic display, the lack of morbidity, and an acceptable radiation dosage. Few technical disadvantages exist. Further application of this unique technique can be predicted."}
{"id": "PMID:201745", "title": "The effect of pancuronium and gallamine on muscarinic transmission in the superior cervical ganglion.", "content": "Pancuronium enhanced contraction of the nictitating membrane elicited via ganglionic muscarinic pathways in the superior cervical ganglion of the cat. In order to elucidate this phenomenon, recordings of the superior cervical ganglion surface potential were made which demonstrated that pancuronium and gallamine reduced and haloperidol enhanced ganglionic hyperpolarization without significantly altering the ganglionic slow depolarization. Pancuronium reversed the effects produced by haloperidol, whereas the latter drug was unable to antagonize those induced by pancuronium. These results allow the speculation that pharmacologically distinct muscarinic receptors reside in sympathetic ganglia, one of which is susceptible to blockade by pancuronium or gallamine.", "contents": "The effect of pancuronium and gallamine on muscarinic transmission in the superior cervical ganglion. Pancuronium enhanced contraction of the nictitating membrane elicited via ganglionic muscarinic pathways in the superior cervical ganglion of the cat. In order to elucidate this phenomenon, recordings of the superior cervical ganglion surface potential were made which demonstrated that pancuronium and gallamine reduced and haloperidol enhanced ganglionic hyperpolarization without significantly altering the ganglionic slow depolarization. Pancuronium reversed the effects produced by haloperidol, whereas the latter drug was unable to antagonize those induced by pancuronium. These results allow the speculation that pharmacologically distinct muscarinic receptors reside in sympathetic ganglia, one of which is susceptible to blockade by pancuronium or gallamine."}
{"id": "PMID:201746", "title": "Substance P and Renshaw cells: a new concept of inhibitory synaptic interactions.", "content": "1. The actions of microelectrophoretically administered substance P on Renshaw cells in pentobarbitone anaesthetized cats were investigated. 2. The effects on spontaneous and synaptic firing and interactions with a number of other agents including acetylcholine, acetyl-beta-methylcholine, acidic amino acids, morphine, dihydro-beta-erythroidine and strychnine were studied in attempts to elucidate the mechanism of action of substance P. 3. Substance P usually selectively depressed the excitation by ACh, and also reduced submaximal synaptically evoked discharges which activate nicotinic receptors, but failed to modify excitation caused either by acetyl-beta-methylcholine, which activates muscarinic receptors, or excitation caused by glutamate or homocysteate. Substance P also depressed excitation by morphine which acted via the nicotinic receptors. 4. The inhibitory effect was not blocked by strychinine and was considered to be unlikely to be due to interaction between the polypeptide and either glycine or GABA receptors. 5. On some cells substance P caused excitation which was blocked by dihydro-beta-erythroidine. Mixed excitatory-inhibitory effects were observed on some of these neurones. 6. The results are discussed in relation to the possibility that substance P could function as a synaptic inhibitory mediator with an unusual selectivity of action.", "contents": "Substance P and Renshaw cells: a new concept of inhibitory synaptic interactions. 1. The actions of microelectrophoretically administered substance P on Renshaw cells in pentobarbitone anaesthetized cats were investigated. 2. The effects on spontaneous and synaptic firing and interactions with a number of other agents including acetylcholine, acetyl-beta-methylcholine, acidic amino acids, morphine, dihydro-beta-erythroidine and strychnine were studied in attempts to elucidate the mechanism of action of substance P. 3. Substance P usually selectively depressed the excitation by ACh, and also reduced submaximal synaptically evoked discharges which activate nicotinic receptors, but failed to modify excitation caused either by acetyl-beta-methylcholine, which activates muscarinic receptors, or excitation caused by glutamate or homocysteate. Substance P also depressed excitation by morphine which acted via the nicotinic receptors. 4. The inhibitory effect was not blocked by strychinine and was considered to be unlikely to be due to interaction between the polypeptide and either glycine or GABA receptors. 5. On some cells substance P caused excitation which was blocked by dihydro-beta-erythroidine. Mixed excitatory-inhibitory effects were observed on some of these neurones. 6. The results are discussed in relation to the possibility that substance P could function as a synaptic inhibitory mediator with an unusual selectivity of action."}
{"id": "PMID:201748", "title": "Calcium requirement for activation of intact aortic smooth muscle.", "content": "1. Elevation of [K(+)](e) induced a contraction of rabbit aorta. If 10 mM-La(3+) was applied to rabbit aortae prior to [K(+)](e) elevation no contraction occurred. When 10 mM-La(3+) was applied simultaneously with, or at short time periods after, elevation of [K(+)](e) graded contractions were obtained whose magnitudes were higher if La(3+) was added at a later stage.2. Net cellular Ca fluxes associated with these graded contractions were measured using (45)Ca as well as atomic absorption. Correlation of the graded contractions with the net inward Ca movements yielded a Ca activation curve for intact arterial smooth muscle cells. The curve was S-shaped with half-maximal activation at a net Ca uptake of 41 mumole/kg wet wt. of aorta and full activation at 64 mumole/kg. If corrections were made for the extracellular space, full activation occurred at a net Ca uptake of 102 mumole/kg smooth muscle cells or roughly 25 mumole in excess of the value calculated to bind to the activation sites on arterial smooth muscle myosin.3. The contractile force of the smooth muscle cells not only depended on the magnitude, but also on the rate of the net Ca uptake.4. Elevation of tissue c-AMP through inhibition of phosphodiesterase greatly reduced both the rate and magnitude of contraction without affecting the size of the high K(+) stimulated Ca influx. It was concluded that high K(+)-induced depolarization activates the rabbit aorta by stimulating a net Ca uptake, and that the degree of activation is modified by c-AMP sensitive Ca accumulation by intracellular organelles.", "contents": "Calcium requirement for activation of intact aortic smooth muscle. 1. Elevation of [K(+)](e) induced a contraction of rabbit aorta. If 10 mM-La(3+) was applied to rabbit aortae prior to [K(+)](e) elevation no contraction occurred. When 10 mM-La(3+) was applied simultaneously with, or at short time periods after, elevation of [K(+)](e) graded contractions were obtained whose magnitudes were higher if La(3+) was added at a later stage.2. Net cellular Ca fluxes associated with these graded contractions were measured using (45)Ca as well as atomic absorption. Correlation of the graded contractions with the net inward Ca movements yielded a Ca activation curve for intact arterial smooth muscle cells. The curve was S-shaped with half-maximal activation at a net Ca uptake of 41 mumole/kg wet wt. of aorta and full activation at 64 mumole/kg. If corrections were made for the extracellular space, full activation occurred at a net Ca uptake of 102 mumole/kg smooth muscle cells or roughly 25 mumole in excess of the value calculated to bind to the activation sites on arterial smooth muscle myosin.3. The contractile force of the smooth muscle cells not only depended on the magnitude, but also on the rate of the net Ca uptake.4. Elevation of tissue c-AMP through inhibition of phosphodiesterase greatly reduced both the rate and magnitude of contraction without affecting the size of the high K(+) stimulated Ca influx. It was concluded that high K(+)-induced depolarization activates the rabbit aorta by stimulating a net Ca uptake, and that the degree of activation is modified by c-AMP sensitive Ca accumulation by intracellular organelles."}
{"id": "PMID:201756", "title": "Quantitative structure-activity relationships in centrally acting imidazolidines structurally related to clonidine.", "content": "The central hypotensive action of clonidine and 26 structurally related derivatives was quantified by means of an ED30 obtained from dose-response curves following intravenous administration to anesthetized, normotensive rats. Multiple regression analyses of the biological data yielded correlation equations comprising a relationship between hypotensive activity and molecular structure. In the equations the pharmacokinetics together with the actual engagement of the central alpha-adrenoceptor are accounted for. More detailed characteristics of this central alpha-adrenoceptor emerged from correlation studies in which new ED30 values, associated with brain concentrations, were employed. The use of this biological parameter at the alpha-adrenoceptor level allowed the presentation of a hypothetical working model for the mechanism of interaction between this receptive site and clonidine-like imidazolidines.", "contents": "Quantitative structure-activity relationships in centrally acting imidazolidines structurally related to clonidine. The central hypotensive action of clonidine and 26 structurally related derivatives was quantified by means of an ED30 obtained from dose-response curves following intravenous administration to anesthetized, normotensive rats. Multiple regression analyses of the biological data yielded correlation equations comprising a relationship between hypotensive activity and molecular structure. In the equations the pharmacokinetics together with the actual engagement of the central alpha-adrenoceptor are accounted for. More detailed characteristics of this central alpha-adrenoceptor emerged from correlation studies in which new ED30 values, associated with brain concentrations, were employed. The use of this biological parameter at the alpha-adrenoceptor level allowed the presentation of a hypothetical working model for the mechanism of interaction between this receptive site and clonidine-like imidazolidines."}
{"id": "PMID:201757", "title": "Molecular orbital studies on the mechanism of drug-receptor interaction. 2. beta-Adrenergic drugs. An approach to explain the role of the aromatic moiety.", "content": "The role of the aromatic moiety of beta-adrenergic drugs in the interaction with the receptor was investigated using the quantum mechanical ab initio SCF-MO-LCAO method. The structure-activity relationship was essentially discussed by analyzing the electrostatic molecular potential of three compounds which constitute meaningful portions of isoproterenol, INPEA, and doberol, the first drug having a stimulating activity and the others a blocking one. The results obtained point out the different roles played in the drug-receptor interaction by the various regions of the drugs and they also show that the aromatic moiety influences both the affinity and the intrinsic activity of the drugs. Indeed, the spatial correspondence among zones with negative potentials, which are localized on the phenyl substitutents of isoproterenol and INPEA and on the phenyl ring of doberol, could contribute to the affinity. On the other hand, the intrinsic activity of isoproterenol might be associated both with the proton-donor tendency of one phenolic OH group and with the wide zone of negative potential which spreads on a large part of the aromati moiety.", "contents": "Molecular orbital studies on the mechanism of drug-receptor interaction. 2. beta-Adrenergic drugs. An approach to explain the role of the aromatic moiety. The role of the aromatic moiety of beta-adrenergic drugs in the interaction with the receptor was investigated using the quantum mechanical ab initio SCF-MO-LCAO method. The structure-activity relationship was essentially discussed by analyzing the electrostatic molecular potential of three compounds which constitute meaningful portions of isoproterenol, INPEA, and doberol, the first drug having a stimulating activity and the others a blocking one. The results obtained point out the different roles played in the drug-receptor interaction by the various regions of the drugs and they also show that the aromatic moiety influences both the affinity and the intrinsic activity of the drugs. Indeed, the spatial correspondence among zones with negative potentials, which are localized on the phenyl substitutents of isoproterenol and INPEA and on the phenyl ring of doberol, could contribute to the affinity. On the other hand, the intrinsic activity of isoproterenol might be associated both with the proton-donor tendency of one phenolic OH group and with the wide zone of negative potential which spreads on a large part of the aromati moiety."}
{"id": "PMID:201758", "title": "1,2,4-Triazole amino nucleosides. 1-beta-D-3'-Amino-3'-deoxyribofuranosyl-1,2,4-triazole-3-carboxamide and related nucleosides.", "content": "The synthesis of 1-beta-D-3'-amino-3'-deoxyribofuranosyl-1,2,4-triazole-3-carboxamide--the 3'-amino analogue of ribavirin--and five related nucleoside analogues is described. Each analogue exhibited LD50 concentrations greater than 100 microgram/mL against P-388 mouse lymphoid leukemia cells in tissue culture. Antiviral testing indicated that none of the compounds exhibited significant activity.", "contents": "1,2,4-Triazole amino nucleosides. 1-beta-D-3'-Amino-3'-deoxyribofuranosyl-1,2,4-triazole-3-carboxamide and related nucleosides. The synthesis of 1-beta-D-3'-amino-3'-deoxyribofuranosyl-1,2,4-triazole-3-carboxamide--the 3'-amino analogue of ribavirin--and five related nucleoside analogues is described. Each analogue exhibited LD50 concentrations greater than 100 microgram/mL against P-388 mouse lymphoid leukemia cells in tissue culture. Antiviral testing indicated that none of the compounds exhibited significant activity."}
{"id": "PMID:201765", "title": "Stimulation of hepatic microsomal metabolism in mice by a mixture of polybrominated biphenyls.", "content": "The pattern of stimulation of hepatic microsomal mixed function oxidases has been studied in female NMRI mice following a single ip injection of 150 mg/kg polybrominated biphenyls (PBBs) and compared to the patterns produced by phenobarbital (PB), 3 X 100 mg/kg; 3-methylcholanthrene (MC), 3 X 20 mg/kg; and these two agents administered together at these doses. Cytochrome P450, ethylmorphine N-demethylase, and epoxide hydratase reached maximums of 200, 200, and 350% of control values, respectively, at 48 hr after treatment with PBBs. Ethoxycoumarin O-deethylase and arylhydrocarbon hydroxylase were maximally increased to 400 and 180% of control values, respectively, 96 hr after PBBs. The reduced cytochrome P450 ethylisocyanide difference spectra and the inhibition of ethoxycoumarin O-deethylase and arylhydrocarbon hydroxylase activity by metyrapone and alpha-naphthoflavone indicated that the characteristics of the cytochrome P450 and the cytochrome P450-dependent enzymes changed with time after administration of PBBs. These results indicate that the enzyme-stimulating properties of PBBs alter, changing from PB-like to MC-like, with time after administration. These findings provide an explanation for the effects of PBBs on the toxicity of bromobenzene, indicating that PBBs represent a new and previously unrecognized calss of toxicity-modifying agents sharing properties of both PB and MC.", "contents": "Stimulation of hepatic microsomal metabolism in mice by a mixture of polybrominated biphenyls. The pattern of stimulation of hepatic microsomal mixed function oxidases has been studied in female NMRI mice following a single ip injection of 150 mg/kg polybrominated biphenyls (PBBs) and compared to the patterns produced by phenobarbital (PB), 3 X 100 mg/kg; 3-methylcholanthrene (MC), 3 X 20 mg/kg; and these two agents administered together at these doses. Cytochrome P450, ethylmorphine N-demethylase, and epoxide hydratase reached maximums of 200, 200, and 350% of control values, respectively, at 48 hr after treatment with PBBs. Ethoxycoumarin O-deethylase and arylhydrocarbon hydroxylase were maximally increased to 400 and 180% of control values, respectively, 96 hr after PBBs. The reduced cytochrome P450 ethylisocyanide difference spectra and the inhibition of ethoxycoumarin O-deethylase and arylhydrocarbon hydroxylase activity by metyrapone and alpha-naphthoflavone indicated that the characteristics of the cytochrome P450 and the cytochrome P450-dependent enzymes changed with time after administration of PBBs. These results indicate that the enzyme-stimulating properties of PBBs alter, changing from PB-like to MC-like, with time after administration. These findings provide an explanation for the effects of PBBs on the toxicity of bromobenzene, indicating that PBBs represent a new and previously unrecognized calss of toxicity-modifying agents sharing properties of both PB and MC."}
{"id": "PMID:201770", "title": "Plasma osmolality and electrolytes during the post partum months in Ghanaian women.", "content": "Plasma osmolality and electrolytes levels were determined in lactating women during the period of 7th week to the 18th month post partum and compared with the levels seen in a control group of non-pregnant non-lactating women of the same age group (18-30 years). On the whole, plasma sodium, chloride and osmolality levels in the lactating women were found to be slightly but significantly elevated, while the plasma potassium levels were lowered. We suggest that these are due to the effects of increased ACTH secretion that occurs during lactation.", "contents": "Plasma osmolality and electrolytes during the post partum months in Ghanaian women. Plasma osmolality and electrolytes levels were determined in lactating women during the period of 7th week to the 18th month post partum and compared with the levels seen in a control group of non-pregnant non-lactating women of the same age group (18-30 years). On the whole, plasma sodium, chloride and osmolality levels in the lactating women were found to be slightly but significantly elevated, while the plasma potassium levels were lowered. We suggest that these are due to the effects of increased ACTH secretion that occurs during lactation."}
{"id": "PMID:201771", "title": "Pulsatile tinnitus: the role of angiography.", "content": "Pulse-synchronous tinnitus is probably due to turbulent blood flow in or around the temporal bone. The anatomy of temporal bone blood supply is reviewed. Eight examples of tinnitus are presented to illustrate the spectrum of lesions that will produce this symptom and the role of angiography in its investigation.", "contents": "Pulsatile tinnitus: the role of angiography. Pulse-synchronous tinnitus is probably due to turbulent blood flow in or around the temporal bone. The anatomy of temporal bone blood supply is reviewed. Eight examples of tinnitus are presented to illustrate the spectrum of lesions that will produce this symptom and the role of angiography in its investigation."}
{"id": "PMID:201774", "title": "Temperature-sensitive growth regulation in one type of transformed rat cells induced by the tsa mutant of polyoma virus.", "content": "A fibroblast line of the 3T3 type with a low saturation density was established from Fisher rat embryo cells. After infection with either wild-type or tsa mutant polyoma virus, transformants were isolated and cloned at 33 degrees C on the basis of their ability either to grow as dense foci on plastic in liquid medium (type N) or to form colonies in soft agar (type A). Polyoma T antigen was detected in all of the transformed lines. The following growth characteristics were studied for both types at 33 and 41 degrees C: saturation density, growth in soft agar and at a low serum concentration, colony-forming ability, and generation time. tsa-N transformants behaved at 33 degrees C similarly to transformed cells, but reverted at 41 degrees C to the nontransformed phenotype for all of these characters. tsa-A transformants and all of the wild-type transformants exhibited the transformed phenotype at both low and high temperatures. These results led us to distinguish at least two types of virus-induced transformants. In one of them, the activity of the protein affected by the tsa mutation appears to be necessary for the expression of several of the characters defining the transformed state.", "contents": "Temperature-sensitive growth regulation in one type of transformed rat cells induced by the tsa mutant of polyoma virus. A fibroblast line of the 3T3 type with a low saturation density was established from Fisher rat embryo cells. After infection with either wild-type or tsa mutant polyoma virus, transformants were isolated and cloned at 33 degrees C on the basis of their ability either to grow as dense foci on plastic in liquid medium (type N) or to form colonies in soft agar (type A). Polyoma T antigen was detected in all of the transformed lines. The following growth characteristics were studied for both types at 33 and 41 degrees C: saturation density, growth in soft agar and at a low serum concentration, colony-forming ability, and generation time. tsa-N transformants behaved at 33 degrees C similarly to transformed cells, but reverted at 41 degrees C to the nontransformed phenotype for all of these characters. tsa-A transformants and all of the wild-type transformants exhibited the transformed phenotype at both low and high temperatures. These results led us to distinguish at least two types of virus-induced transformants. In one of them, the activity of the protein affected by the tsa mutation appears to be necessary for the expression of several of the characters defining the transformed state."}
{"id": "PMID:201775", "title": "Genetic relatedness of equine herpesvirus types 1 and 3.", "content": "The genetic relatedness of two types of equine herpesviruses (EHVs), 1 (EHV-1) and 3 (EHV-3), was determined by DNA-DNA reassociation kinetics. Denatured, labeled viral DNA probe was allowed to reassociate in the presence or absence of the second unlabeled viral DNA. The initial rate of reassociation of either labeled viral DNA was increased by the presence of the heterologous viral DNA to an extent indicating only 2 to 5% homology between the two EHV genomes. Moreover, labeled RNA extracted from EHV-3-infected cells hybridized to filter-immobilized EHV-1 DNA only 2 to 3 percent as efficiently as to the homologous EHV-3 DNA. These results demonstrate that the genital (EHV-3) and nongenital (EHV-1) types of EHVs exhibit very little genetic homology.", "contents": "Genetic relatedness of equine herpesvirus types 1 and 3. The genetic relatedness of two types of equine herpesviruses (EHVs), 1 (EHV-1) and 3 (EHV-3), was determined by DNA-DNA reassociation kinetics. Denatured, labeled viral DNA probe was allowed to reassociate in the presence or absence of the second unlabeled viral DNA. The initial rate of reassociation of either labeled viral DNA was increased by the presence of the heterologous viral DNA to an extent indicating only 2 to 5% homology between the two EHV genomes. Moreover, labeled RNA extracted from EHV-3-infected cells hybridized to filter-immobilized EHV-1 DNA only 2 to 3 percent as efficiently as to the homologous EHV-3 DNA. These results demonstrate that the genital (EHV-3) and nongenital (EHV-1) types of EHVs exhibit very little genetic homology."}
{"id": "PMID:201776", "title": "Slow switchover from host RNA synthesis to bacteriophage RNA synthesis after infection of Escherichia coli with a T4 mutant defective in the bacteriophage T4-induced unfolding of the host nucleoid.", "content": "Most, if not all, host RNA synthesis was shut off after infection of Escherichia coli strain B/5 with a bacteriophage T4 multiple mutant defective in the abilities to induce (i) unfolding of the host nucleoid (unf-), (ii) nuclear disruption (ndd-), and (iii) host DNA degradation (denA-, denB-). The shutoff of host RNA synthesis and turn-on of phage RNA synthesis were slower after infection of E. coli with unf- phage than after infection with unf+ phage. This delay in the switchover from host RNA synthesis to phage RNA synthesis in unf- infections did not result in a measurable delay in the onset of nuclear disruption, deoxyribonucleoside monophosphate kinase synthesis, or DNA synthesis. unf39 did not complement alc (allows late transcription on cytosine-containing DNA) mutants, supporting the proposal of Sirotkin et al. [Nature (London) 265:28-32, 1977] that alc and unf are possibly the same gene.", "contents": "Slow switchover from host RNA synthesis to bacteriophage RNA synthesis after infection of Escherichia coli with a T4 mutant defective in the bacteriophage T4-induced unfolding of the host nucleoid. Most, if not all, host RNA synthesis was shut off after infection of Escherichia coli strain B/5 with a bacteriophage T4 multiple mutant defective in the abilities to induce (i) unfolding of the host nucleoid (unf-), (ii) nuclear disruption (ndd-), and (iii) host DNA degradation (denA-, denB-). The shutoff of host RNA synthesis and turn-on of phage RNA synthesis were slower after infection of E. coli with unf- phage than after infection with unf+ phage. This delay in the switchover from host RNA synthesis to phage RNA synthesis in unf- infections did not result in a measurable delay in the onset of nuclear disruption, deoxyribonucleoside monophosphate kinase synthesis, or DNA synthesis. unf39 did not complement alc (allows late transcription on cytosine-containing DNA) mutants, supporting the proposal of Sirotkin et al. [Nature (London) 265:28-32, 1977] that alc and unf are possibly the same gene."}
{"id": "PMID:201777", "title": "Two methyltransferase activities in the purified virions of vesicular stomatitis virus.", "content": "In addition to an RNA-dependent RNA polymerase, purified vesicular stomatitis virus contains a methyltransferase activity which transfers the methyl group from the methyl donor, S-adenosyl-L-methionine, to two positions in the 5'-terminal capped structure of the nascent mRNA's synthesized in vitro as 7mG-(5)'ppp(5')Apm... In the present study it is shown that two distinct methyltransferase activities are discernible in the purified virus. The in vitro concentrations of the methyl donor specify the number and location of the methyl groups transferred to the capped 5'-termini of VSV mRNA's. Limited concentrations of the methyl donor result in a single methylation of the penultimate base in the 2'-hydroxyl position, that is, G(5')ppp(5')Apm..., whereas saturating concentrations of the methyl donor methylate the blocking guanosine residue at the 7-position, resulting in the dimethylated cap, 7mG(5')ppp(5')Apm... Pulse-chase experiments demonstrate that the monomethylated cap structure is the precursor substrate for the dimethylated cap. In this respect, vesicular stomatitis virus system is quite distinct from the vaccinia and reovirus systems. Virus purified from different host cells including hamster, mouse, and human contain both methyltransferase activities. The mRNA's containing monomethylated capped structures are poor templates for protein synthesis in vitro.", "contents": "Two methyltransferase activities in the purified virions of vesicular stomatitis virus. In addition to an RNA-dependent RNA polymerase, purified vesicular stomatitis virus contains a methyltransferase activity which transfers the methyl group from the methyl donor, S-adenosyl-L-methionine, to two positions in the 5'-terminal capped structure of the nascent mRNA's synthesized in vitro as 7mG-(5)'ppp(5')Apm... In the present study it is shown that two distinct methyltransferase activities are discernible in the purified virus. The in vitro concentrations of the methyl donor specify the number and location of the methyl groups transferred to the capped 5'-termini of VSV mRNA's. Limited concentrations of the methyl donor result in a single methylation of the penultimate base in the 2'-hydroxyl position, that is, G(5')ppp(5')Apm..., whereas saturating concentrations of the methyl donor methylate the blocking guanosine residue at the 7-position, resulting in the dimethylated cap, 7mG(5')ppp(5')Apm... Pulse-chase experiments demonstrate that the monomethylated cap structure is the precursor substrate for the dimethylated cap. In this respect, vesicular stomatitis virus system is quite distinct from the vaccinia and reovirus systems. Virus purified from different host cells including hamster, mouse, and human contain both methyltransferase activities. The mRNA's containing monomethylated capped structures are poor templates for protein synthesis in vitro."}
{"id": "PMID:201778", "title": "Polypeptides of the surface projections and the ribonucleoprotein of avian infectious bronchitis virus.", "content": "Purified avian infectious bronchitis virus was digested with bromelain (0.7 mg/ml), and the surface projections were removed. Polyacrylamide gel electrophoresis of the polypeptides from these bromelain-treated particles showed that VP1, VP2, and VP5 were missing from the seven polypeptides. VP1 to VP7, that were present in untreated virus preparations. Milder bromelain treatment (0.07 mg/ml) left visible surface projections and polypeptides comprising VP1 and VP2 intact, but removed VP5. Thus, there are apparently two types of surface projections on the virus particle. The ribonucleoprotein complex was released from virus particles disrupted with 1% Nonidet P-40. The proportion of VP6 in such preparations was greatly reduced, implying that VP6 is the structural polypeptide of the ribonucleoprotein. Polypeptides VP1, VP2, VP4, and VP5 are glycosylated, but none of the polypeptides contains lipid.", "contents": "Polypeptides of the surface projections and the ribonucleoprotein of avian infectious bronchitis virus. Purified avian infectious bronchitis virus was digested with bromelain (0.7 mg/ml), and the surface projections were removed. Polyacrylamide gel electrophoresis of the polypeptides from these bromelain-treated particles showed that VP1, VP2, and VP5 were missing from the seven polypeptides. VP1 to VP7, that were present in untreated virus preparations. Milder bromelain treatment (0.07 mg/ml) left visible surface projections and polypeptides comprising VP1 and VP2 intact, but removed VP5. Thus, there are apparently two types of surface projections on the virus particle. The ribonucleoprotein complex was released from virus particles disrupted with 1% Nonidet P-40. The proportion of VP6 in such preparations was greatly reduced, implying that VP6 is the structural polypeptide of the ribonucleoprotein. Polypeptides VP1, VP2, VP4, and VP5 are glycosylated, but none of the polypeptides contains lipid."}
{"id": "PMID:201779", "title": "Replication of Epstein-Barr virus: ultrastructural and immunofluorescent studies of P3HR1-superinfected Raji cells.", "content": "We have studied by means of electron microscopy and immunofluorescence the different steps of the replication of the P3HR1 strain of Epstein-Barr virus in Raji cells. The virus entered the cell by fusion of the viral envelope with the plasma membrane, followed by the disintegration of the capsid. In some cases, the migration of nucleocapsids toward the nuclear membrane was observed. The synthesis of new virions began as early as 7 h after infection (in the case of a high multiplicity of infection [MOI]-800 particles per cell) and took place in low-electron-density areas of the nucleus. A viral envelope was acquired by budding either through the nuclear membrane or more often through membranes of the Golgi apparatus or cytoplasmic vacuoles. Comparing immunofluorescence and electron microscopic data a good correlation was found between the presence of early antigen and ultrastructurally altered cells, as well as between the presence of viral capsid antigen and virus-producing cells. With different MOIs, different types of viral cycles were observed: at a low MOI (less than or equal to 50 particles per cell), a nonproducer cycle was induced, with early antigen synthesis only; at a higher MOI (100 particles per cell), a transient production of a small amount of virions was observed, and at a high MOI (greater than or equal to 300 particles per cell), a productive cycle was the rule.", "contents": "Replication of Epstein-Barr virus: ultrastructural and immunofluorescent studies of P3HR1-superinfected Raji cells. We have studied by means of electron microscopy and immunofluorescence the different steps of the replication of the P3HR1 strain of Epstein-Barr virus in Raji cells. The virus entered the cell by fusion of the viral envelope with the plasma membrane, followed by the disintegration of the capsid. In some cases, the migration of nucleocapsids toward the nuclear membrane was observed. The synthesis of new virions began as early as 7 h after infection (in the case of a high multiplicity of infection [MOI]-800 particles per cell) and took place in low-electron-density areas of the nucleus. A viral envelope was acquired by budding either through the nuclear membrane or more often through membranes of the Golgi apparatus or cytoplasmic vacuoles. Comparing immunofluorescence and electron microscopic data a good correlation was found between the presence of early antigen and ultrastructurally altered cells, as well as between the presence of viral capsid antigen and virus-producing cells. With different MOIs, different types of viral cycles were observed: at a low MOI (less than or equal to 50 particles per cell), a nonproducer cycle was induced, with early antigen synthesis only; at a higher MOI (100 particles per cell), a transient production of a small amount of virions was observed, and at a high MOI (greater than or equal to 300 particles per cell), a productive cycle was the rule."}
{"id": "PMID:201780", "title": "Structural protein markers in the avian oncoviruses.", "content": "The proteins of purified avian oncoviruses were analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and isoelectric focusing. Certain members of the avian leukosis-sarcoma viruses (ALSV) had group-specific antigens with altered electrophoretic properties. (i) The p27 protein of Rous-associated virus 0 (RAV-0) had a lower electrophoretic mobility in SDS gels and a lower isoelectric point than the p27 of other ALSV. (ii) The p19 proteins of RAV-1, RAV-2, and the Bryan high-titer strain of Rous sarcoma virus had higher mobilities in SDS gels than did the corresponding protein of other viruses. This altered electrophoretic mobility was correlated with specific differences in the tryptic peptides of radioiodinated p19s. (iii) The p15 protein of RAV-7 had a lower mobility in SDS gels than did the p15 of other ALSV. These markers were used in a study of the structural proteins of subgroup E RAV-60 produced after infection of chicken embryo cells by exogenous ALSV. Although exogenous group-specific protein markers could often be identified in the subgroup E isolates, one RAV-60 had a p27 that comigrated with the p27 of RAV-0. The p19s of two other RAV-60 isolates had electrophoretic properties that were different than those of p19s from either RAV-0 or the exogenous viruses. These results support the hypothesis that RAV-60 is generated by recombination between endogenous and exogenous oncoviruses and indicate that at least the p27 encoded by RAV-0 is closely related to a protein specified by endogenous viral information in chicken cells.", "contents": "Structural protein markers in the avian oncoviruses. The proteins of purified avian oncoviruses were analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and isoelectric focusing. Certain members of the avian leukosis-sarcoma viruses (ALSV) had group-specific antigens with altered electrophoretic properties. (i) The p27 protein of Rous-associated virus 0 (RAV-0) had a lower electrophoretic mobility in SDS gels and a lower isoelectric point than the p27 of other ALSV. (ii) The p19 proteins of RAV-1, RAV-2, and the Bryan high-titer strain of Rous sarcoma virus had higher mobilities in SDS gels than did the corresponding protein of other viruses. This altered electrophoretic mobility was correlated with specific differences in the tryptic peptides of radioiodinated p19s. (iii) The p15 protein of RAV-7 had a lower mobility in SDS gels than did the p15 of other ALSV. These markers were used in a study of the structural proteins of subgroup E RAV-60 produced after infection of chicken embryo cells by exogenous ALSV. Although exogenous group-specific protein markers could often be identified in the subgroup E isolates, one RAV-60 had a p27 that comigrated with the p27 of RAV-0. The p19s of two other RAV-60 isolates had electrophoretic properties that were different than those of p19s from either RAV-0 or the exogenous viruses. These results support the hypothesis that RAV-60 is generated by recombination between endogenous and exogenous oncoviruses and indicate that at least the p27 encoded by RAV-0 is closely related to a protein specified by endogenous viral information in chicken cells."}
{"id": "PMID:201781", "title": "Effects of filipin on the structure and biological activity of enveloped viruses.", "content": "The interaction of the polyene antibiotic filipin with membrane-bound cholesterol in vesicular stomatitis (VS), influenza, and Rauscher leukemia virions was studied. Exposure of virions to filipin resulted in a series of depressions and ridges in the envelope of VS virions, with a periodicity of 15 to 20 nm perpendicular to the long axis of the particle; similar morphological alterations were observed in negatively stained preparations, in thin-sectioned virions, and in protease-treated virions that lack surface glycoproteins. This morphological effect was specific for filipin, since the envelopes of VS virions that had been treated with another polyene antibiotic, amphotericin B, exhibited markedly different morphology. Morphological alterations induced by filipin in influenza and Rauscher leukemia virions differed from those seen in VS virions. The infectivity of filipin-treated VS virions was reduced up to 500-fold, whereas influenza virions were resistant to filipin treatment. Incorporation of filipin into the virions was demonstrated, and no release of either lipids or proteins from virions was detected after filipin treatment. A stoichiometry of approximately 1 mol of bound filipin per mol of cholesterol was found in both intact and protease-treated VS virions. The equilibrium dissociation constant for filipin-cholesterol interaction was approximately 74-fold larger in intact than in protease-treated VS virions. The initial rate of association of filipin with cholesterol in intact virions was slower than that in protease-treated particles. The fluidity of lipids in VS viral membranes, as probed by a stearic acid derivative spin label, was markedly reduced when either intact or protease-treated virions were treated with filipin.", "contents": "Effects of filipin on the structure and biological activity of enveloped viruses. The interaction of the polyene antibiotic filipin with membrane-bound cholesterol in vesicular stomatitis (VS), influenza, and Rauscher leukemia virions was studied. Exposure of virions to filipin resulted in a series of depressions and ridges in the envelope of VS virions, with a periodicity of 15 to 20 nm perpendicular to the long axis of the particle; similar morphological alterations were observed in negatively stained preparations, in thin-sectioned virions, and in protease-treated virions that lack surface glycoproteins. This morphological effect was specific for filipin, since the envelopes of VS virions that had been treated with another polyene antibiotic, amphotericin B, exhibited markedly different morphology. Morphological alterations induced by filipin in influenza and Rauscher leukemia virions differed from those seen in VS virions. The infectivity of filipin-treated VS virions was reduced up to 500-fold, whereas influenza virions were resistant to filipin treatment. Incorporation of filipin into the virions was demonstrated, and no release of either lipids or proteins from virions was detected after filipin treatment. A stoichiometry of approximately 1 mol of bound filipin per mol of cholesterol was found in both intact and protease-treated VS virions. The equilibrium dissociation constant for filipin-cholesterol interaction was approximately 74-fold larger in intact than in protease-treated VS virions. The initial rate of association of filipin with cholesterol in intact virions was slower than that in protease-treated particles. The fluidity of lipids in VS viral membranes, as probed by a stearic acid derivative spin label, was markedly reduced when either intact or protease-treated virions were treated with filipin."}
{"id": "PMID:201782", "title": "Uncoating and gene expression of simian virus 40 in CV-1 cell nuclei inoculated by microinjection.", "content": "CV-1 cells were inoculated with simian virus 40 virus within the nucleus or cytoplasm by microinjection. Virions were uncoated with great efficiency within the cell nucleus.", "contents": "Uncoating and gene expression of simian virus 40 in CV-1 cell nuclei inoculated by microinjection. CV-1 cells were inoculated with simian virus 40 virus within the nucleus or cytoplasm by microinjection. Virions were uncoated with great efficiency within the cell nucleus."}
{"id": "PMID:201783", "title": "Transformation-defective mutants of Rous sarcoma virus with src gene deletions of varying length.", "content": "The RNAs of transformation-defective (td) deletion mutants of the Schmidt-Ruppin strain of Rous sarcoma virus were found to vary in size when compared by polyacrylamide gel electrophoresis. Three of seven td mutants appeared to recombine with a mutant of Rous sarcoma virus (Schmidt-Ruppin), which has a temperature-sensitive sarcoma (src) gene and is termed ts68, to give rise to recombinants with a reduced temperature sensitivity. The results suggested that different clones of td mutants exist: some in which the src gene appears to be deleted, and others in which the src gene is only partially deleted. A direct correlation between RNA size and the extent of src gene deletion measured by recombination was not obtained, possibly because the recombination assay could only detect src sequences homologous to the lesion(s) of ts68, whereas the electrophoretic analysis of the RNA measured src deletions as well as other possible alterations of the RNA.", "contents": "Transformation-defective mutants of Rous sarcoma virus with src gene deletions of varying length. The RNAs of transformation-defective (td) deletion mutants of the Schmidt-Ruppin strain of Rous sarcoma virus were found to vary in size when compared by polyacrylamide gel electrophoresis. Three of seven td mutants appeared to recombine with a mutant of Rous sarcoma virus (Schmidt-Ruppin), which has a temperature-sensitive sarcoma (src) gene and is termed ts68, to give rise to recombinants with a reduced temperature sensitivity. The results suggested that different clones of td mutants exist: some in which the src gene appears to be deleted, and others in which the src gene is only partially deleted. A direct correlation between RNA size and the extent of src gene deletion measured by recombination was not obtained, possibly because the recombination assay could only detect src sequences homologous to the lesion(s) of ts68, whereas the electrophoretic analysis of the RNA measured src deletions as well as other possible alterations of the RNA."}
{"id": "PMID:201786", "title": "Clinical evaluation of pivmecillinam in intractable urinary-tract infections with complications. A comparative study with amoxicillin by a randomized double-blind technique.", "content": "A comparative study was made by the double-blind technique in order to make clear the usefulness of pivmecillinam in the treatment of intractable complicated urinary-tract infections using amoxicillin as a reference drug. Pivmecillinam was given in dosage of 400 mg (potency) per day which was one-fifth the dose of amoxicillin 2,000 mg (potency) per day. In global judgement, pivmecillinam was found superior to amoxicillin. It showed a \"significant\" superiority over amoxicillin for the treatment of, among others, the urinary-tract infections after prostatectomy, which are intractable diseases. When evaluated by symptoms, pivmecillinam improved bacteriuria \"significantly\" better than amoxicillin. When seen by causative organisms, the pivmecillinam treatment was \"significantly\" superior to the amoxicillin treatment against E. coli infections. Pivmecillinam was active against amoxicillin-resistant E. coli. Incidence of adverse reactions was less frequent with pivmecillinam than with amoxicillin. These results indicate that pivmecillinam is a drug of high usefulness for the treatment of intractable complicated urinary-tract infections when evaluated using amoxicillin as a reference drug.", "contents": "Clinical evaluation of pivmecillinam in intractable urinary-tract infections with complications. A comparative study with amoxicillin by a randomized double-blind technique. A comparative study was made by the double-blind technique in order to make clear the usefulness of pivmecillinam in the treatment of intractable complicated urinary-tract infections using amoxicillin as a reference drug. Pivmecillinam was given in dosage of 400 mg (potency) per day which was one-fifth the dose of amoxicillin 2,000 mg (potency) per day. In global judgement, pivmecillinam was found superior to amoxicillin. It showed a \"significant\" superiority over amoxicillin for the treatment of, among others, the urinary-tract infections after prostatectomy, which are intractable diseases. When evaluated by symptoms, pivmecillinam improved bacteriuria \"significantly\" better than amoxicillin. When seen by causative organisms, the pivmecillinam treatment was \"significantly\" superior to the amoxicillin treatment against E. coli infections. Pivmecillinam was active against amoxicillin-resistant E. coli. Incidence of adverse reactions was less frequent with pivmecillinam than with amoxicillin. These results indicate that pivmecillinam is a drug of high usefulness for the treatment of intractable complicated urinary-tract infections when evaluated using amoxicillin as a reference drug."}
{"id": "PMID:201792", "title": "Effect of diltiazem on insulin secretion. I. Experiments in vitro.", "content": "Effect of diltiazem on glucose-induced insulin secretion was investigated in the rat islets of Langerhans isolated by a collagenase digestion technique. It was found that B-cells, main constituents of isolated islet preparations, had a well-preserved ultrastructural appearance immediately following isolation or after incubation with glucose or glucose and diltiazem. The islets released a large amount of insulin upon stimulation with glucose and CaCl2. Diltiazem (10(-6)-10(-4) M) produced a dose-related inhibition of glucose-induced insulin secretion and this effect was antagonized by the increase in extracellular concentration of CaCl2. The inhibitory effect of diltiazem on the insulin secretion was also counteracted by dibutyryl-3',5'-cyclic AMP or by theophylline. Among calcium-antagonists tested, nifedipine produced the most powerful inhibitory action on the insulin secretion, while the effect of verapamil was similar to or somewhat stronger than that of diltiazem. It was suggested that diltiazem may reduce the intracellular concentration of free calcium ion, thus causing an inhibitory effect on the glucose-induced insulin secretion by the isolated islets of Langerhans.", "contents": "Effect of diltiazem on insulin secretion. I. Experiments in vitro. Effect of diltiazem on glucose-induced insulin secretion was investigated in the rat islets of Langerhans isolated by a collagenase digestion technique. It was found that B-cells, main constituents of isolated islet preparations, had a well-preserved ultrastructural appearance immediately following isolation or after incubation with glucose or glucose and diltiazem. The islets released a large amount of insulin upon stimulation with glucose and CaCl2. Diltiazem (10(-6)-10(-4) M) produced a dose-related inhibition of glucose-induced insulin secretion and this effect was antagonized by the increase in extracellular concentration of CaCl2. The inhibitory effect of diltiazem on the insulin secretion was also counteracted by dibutyryl-3',5'-cyclic AMP or by theophylline. Among calcium-antagonists tested, nifedipine produced the most powerful inhibitory action on the insulin secretion, while the effect of verapamil was similar to or somewhat stronger than that of diltiazem. It was suggested that diltiazem may reduce the intracellular concentration of free calcium ion, thus causing an inhibitory effect on the glucose-induced insulin secretion by the isolated islets of Langerhans."}
{"id": "PMID:201796", "title": "Serologic study on the prevalence of murine viruses in five Canadian mouse colonies.", "content": "A serologic study was made of five Canadian mouse colonies to determine the prevalence of antibodies to 11 murine viruses. A total of 139 sera from the five colonies were evaluated by complement fixation or hemagglutination inhibition methods. Viral antibodies were present in all five colonies. Antibodies to pneumonia virus of mice, minute virus of mice, Theiler's encephalomyelitis virus, and reovirus type 3 were found in all five colonies. K-virus antibodies were present in four colonies. Polyoma virus antibodies were found in two colonies and Sendai virus antibodies in two other colonies. Mouse hepatitis virus antibodies were present at a low prevalence in three of the five colonies. No antibodies to adenovirus, lymphocytic choriomeningitis virus, and ectromelia were detected in any of the colonies.", "contents": "Serologic study on the prevalence of murine viruses in five Canadian mouse colonies. A serologic study was made of five Canadian mouse colonies to determine the prevalence of antibodies to 11 murine viruses. A total of 139 sera from the five colonies were evaluated by complement fixation or hemagglutination inhibition methods. Viral antibodies were present in all five colonies. Antibodies to pneumonia virus of mice, minute virus of mice, Theiler's encephalomyelitis virus, and reovirus type 3 were found in all five colonies. K-virus antibodies were present in four colonies. Polyoma virus antibodies were found in two colonies and Sendai virus antibodies in two other colonies. Mouse hepatitis virus antibodies were present at a low prevalence in three of the five colonies. No antibodies to adenovirus, lymphocytic choriomeningitis virus, and ectromelia were detected in any of the colonies."}
{"id": "PMID:201797", "title": "The starfish (Patiria and Pisaster) oocyte: a model system for the study of hormone-surface interaction in oogenesis.", "content": "Studies were made to determine if the starfish (Patiria and Pisaster) oocyte could serve as a model system for investigations of hormone-surface interactions in eucaryotic cells. Treatment of starfisch oocytes with maturation inducing hormone, 1-methyladenine, was observed by scanning electron microscopy to induce surface alteration. The action of the hormone was dependent on the presence of the cation Ca++. Although caffeine, theophylline, and theobromine supposedly inhibit maturation of oocytes, studies using the starfish oocyte showed that theobromine does not inhibit maturation and the inhibition caused by caffeine and theophylline is reversible. Other studies using the starfish oocyte and tritiated 1-methyladenine showed that the hormone does not dissociate from the oocyte once bound, and that the oocyte surface may have multiple receptors for 1-methyladenine. From these studies it was concluded that the starfish oocyte is a useful model for studies of hormone-surface interactions in eucaryotic cells.", "contents": "The starfish (Patiria and Pisaster) oocyte: a model system for the study of hormone-surface interaction in oogenesis. Studies were made to determine if the starfish (Patiria and Pisaster) oocyte could serve as a model system for investigations of hormone-surface interactions in eucaryotic cells. Treatment of starfisch oocytes with maturation inducing hormone, 1-methyladenine, was observed by scanning electron microscopy to induce surface alteration. The action of the hormone was dependent on the presence of the cation Ca++. Although caffeine, theophylline, and theobromine supposedly inhibit maturation of oocytes, studies using the starfish oocyte showed that theobromine does not inhibit maturation and the inhibition caused by caffeine and theophylline is reversible. Other studies using the starfish oocyte and tritiated 1-methyladenine showed that the hormone does not dissociate from the oocyte once bound, and that the oocyte surface may have multiple receptors for 1-methyladenine. From these studies it was concluded that the starfish oocyte is a useful model for studies of hormone-surface interactions in eucaryotic cells."}
{"id": "PMID:201798", "title": "Nonhuman primates: laboratory animals of choice for neurophysiologic studies of sleep.", "content": "A systematic study was made of several nonhuman primates to learn more about their relative usefulness for studies of sleep. Species studied included the Guinea baboon (Papio papio), Kenya or yellow baboon (P cynocephalus), olive baboon (P anubis), sacred baboon (P hamadryas), vervet monkey (Cercopithecus aethiops), rhesus monkey (Macaca mulatta), bonnet monkey (M radiata), crab-eating monkey (M fascicularis), patas monkey (Erythrocebus patas), chimpanzee (Pan troglodytes), mongoose lemur (Lemur mongoz), black lemur (Lemur macaco fulvus), and bushbaby (Galago senegalensis). Comparisons were made of electroencephalographic activity, states of vigilance, and responses to sleep-waking drugs. The results showed that there were major similarities among the genera studied as well as individual intrageneric and intraspecies differences. It was concluded that the chimpanzee, olive baboon, and rhesus monkey were the best species for comparative studies, and that the rhesus monkey was the best single model because of its well defined sleep organization and ease of handling and housing.", "contents": "Nonhuman primates: laboratory animals of choice for neurophysiologic studies of sleep. A systematic study was made of several nonhuman primates to learn more about their relative usefulness for studies of sleep. Species studied included the Guinea baboon (Papio papio), Kenya or yellow baboon (P cynocephalus), olive baboon (P anubis), sacred baboon (P hamadryas), vervet monkey (Cercopithecus aethiops), rhesus monkey (Macaca mulatta), bonnet monkey (M radiata), crab-eating monkey (M fascicularis), patas monkey (Erythrocebus patas), chimpanzee (Pan troglodytes), mongoose lemur (Lemur mongoz), black lemur (Lemur macaco fulvus), and bushbaby (Galago senegalensis). Comparisons were made of electroencephalographic activity, states of vigilance, and responses to sleep-waking drugs. The results showed that there were major similarities among the genera studied as well as individual intrageneric and intraspecies differences. It was concluded that the chimpanzee, olive baboon, and rhesus monkey were the best species for comparative studies, and that the rhesus monkey was the best single model because of its well defined sleep organization and ease of handling and housing."}
{"id": "PMID:201799", "title": "Nerve abscess in lepromatous leprosy. A case report and a discussion of pathogenesis.", "content": "An instance of nerve abscesses developing in a patient with lepromatous leprosy is reported. The pathogenesis of nerve abscess in lepromatous leprosy is briefly discussed. It appears that such abscesses may develop (i) from an ENL lesion in the nerve during ENL reaction, (ii) because of exacerbation of existing lepromatous lesion, (iii) arise as an \"exacerbation nodule\", (iv) due to quiet necrosis in a lepromatous granuloma, or (v) it may be iatrogenic.", "contents": "Nerve abscess in lepromatous leprosy. A case report and a discussion of pathogenesis. An instance of nerve abscesses developing in a patient with lepromatous leprosy is reported. The pathogenesis of nerve abscess in lepromatous leprosy is briefly discussed. It appears that such abscesses may develop (i) from an ENL lesion in the nerve during ENL reaction, (ii) because of exacerbation of existing lepromatous lesion, (iii) arise as an \"exacerbation nodule\", (iv) due to quiet necrosis in a lepromatous granuloma, or (v) it may be iatrogenic."}
{"id": "PMID:201807", "title": "Hormonal regulation of membrane phenotype.", "content": "Incubation of rat hepatoma cells (HTC) in tissue culture with glucocorticoids alters several membrane properties characteristic of transformed cells, without affecting the growth rate of these cells. Variant cell lines resistant to dexamethasone inhibition of plasminogen activator production have been isolated using an agar-fibrin overlay technique to detect plasminogen activator production by individual colonies of HTC cells. The resistance of dexamethasone is not secondary to abnormal or absent glucocorticoid receptors, but due to a lesion in a later step in hormone action specific for plasminogen activator. These variants should prove useful for the study of the mechanism of steroid action as well as for the analysis of the role of proteases in the hormonal regulation of membrane function.", "contents": "Hormonal regulation of membrane phenotype. Incubation of rat hepatoma cells (HTC) in tissue culture with glucocorticoids alters several membrane properties characteristic of transformed cells, without affecting the growth rate of these cells. Variant cell lines resistant to dexamethasone inhibition of plasminogen activator production have been isolated using an agar-fibrin overlay technique to detect plasminogen activator production by individual colonies of HTC cells. The resistance of dexamethasone is not secondary to abnormal or absent glucocorticoid receptors, but due to a lesion in a later step in hormone action specific for plasminogen activator. These variants should prove useful for the study of the mechanism of steroid action as well as for the analysis of the role of proteases in the hormonal regulation of membrane function."}
{"id": "PMID:201808", "title": "Relationship between thymidine transport and phosphorylation in Novikoff rat hepatoma cells as analyzed by a rapid sampling technique.", "content": "Incorporation of thymidine into Novikoff rat hepatoma cells was analyzed with a rapid sampling technique which allowed collection of 12 time points in 20 sec. Transport was a rapid, saturable, nonconcentrative process with a Km of about 85 micrometer. The intracellular thymidine pool was also rapidly labeled in cells which phosphorylated thymidine, that a group translocation process involving thymidine kinase can be ruled out. Under all conditions examined, phosphorylation, not the transport, of thymidine was the rate-determining step in its incorporation into the acid-soluble pool. Estimation of transport rates from total incorporation into cells which phosphorylate the substrate is invalid in this cell system and must be questioned in all instances.", "contents": "Relationship between thymidine transport and phosphorylation in Novikoff rat hepatoma cells as analyzed by a rapid sampling technique. Incorporation of thymidine into Novikoff rat hepatoma cells was analyzed with a rapid sampling technique which allowed collection of 12 time points in 20 sec. Transport was a rapid, saturable, nonconcentrative process with a Km of about 85 micrometer. The intracellular thymidine pool was also rapidly labeled in cells which phosphorylated thymidine, that a group translocation process involving thymidine kinase can be ruled out. Under all conditions examined, phosphorylation, not the transport, of thymidine was the rate-determining step in its incorporation into the acid-soluble pool. Estimation of transport rates from total incorporation into cells which phosphorylate the substrate is invalid in this cell system and must be questioned in all instances."}
{"id": "PMID:201809", "title": "The glucagonoma syndrome and its management.", "content": "The glucagonoma syndrome occurs in some but not all patients with a benign or malignant islet cell tumor and hyperglucagonemia. Manifestations may include anemia, diabetes mellitus, pruritic skin rash, glossitis, stomatitis, weight loss, diarrhea, flexible fingernails, venous thromboses, low plasma amino acid levels, and coarse folds of the jejunum and ileum. Most patients are postmenopausal women, but men and women ages 40 to 65 have been affected. The course is variable depending upon the nature of the underlying tumor. Twenty-two cases of probable glucagonoma syndrome have been reported; twelve documented with glucagon levels. The hyperglucagonemia results from elevation of the proglucagon and true glucagon immunoreactive fractions of pancreatic glucagon. Management of the rash can be accomplished rarely with topical or systemic antibiotics or corticosteroids. If the tumor is resectable, surgery reverses the syndrome. Patients with metastatic disease have responded to streptozotocin and DTIC.", "contents": "The glucagonoma syndrome and its management. The glucagonoma syndrome occurs in some but not all patients with a benign or malignant islet cell tumor and hyperglucagonemia. Manifestations may include anemia, diabetes mellitus, pruritic skin rash, glossitis, stomatitis, weight loss, diarrhea, flexible fingernails, venous thromboses, low plasma amino acid levels, and coarse folds of the jejunum and ileum. Most patients are postmenopausal women, but men and women ages 40 to 65 have been affected. The course is variable depending upon the nature of the underlying tumor. Twenty-two cases of probable glucagonoma syndrome have been reported; twelve documented with glucagon levels. The hyperglucagonemia results from elevation of the proglucagon and true glucagon immunoreactive fractions of pancreatic glucagon. Management of the rash can be accomplished rarely with topical or systemic antibiotics or corticosteroids. If the tumor is resectable, surgery reverses the syndrome. Patients with metastatic disease have responded to streptozotocin and DTIC."}
{"id": "PMID:201812", "title": "[Bilateral salivary duct carcinoma of the parotid gland (author's transl)].", "content": "A case of bilateral carcinoma of the salivary duct is presented. The histological appearance of this rare tumor and the therapeutical consequences are reviewed.", "contents": "[Bilateral salivary duct carcinoma of the parotid gland (author's transl)]. A case of bilateral carcinoma of the salivary duct is presented. The histological appearance of this rare tumor and the therapeutical consequences are reviewed."}
{"id": "PMID:201816", "title": "p-Chlorophenoxyisobutyrate enhanced retention of homologous lipoproteins by human aortic smooth muscle cells.", "content": "Human aortic smooth muscle cells (SMC) specifically bind and take up indiscriminately both the lipid and protein moieties of homologous 25I-very low density lipoproteins (VLDL) and 125I-low density lipoproteins LDL). Sixty-five to 80% of absorbed lipids are incorporated into the cell lipids, preferentially into the phospholipid fraction. Twenty to 35% of the lipid bound and the protein moiety are eliminated from the cells. Half of the eliminated protein label is recovered as TCA soluble products. Five mM of p-chlorophenoxyisobutyrate (CPIB) raise the level of intracellular radioactivity derived from the lipid moieties of VLDL and LDL by about 40% via a reduced elimination. The processing of the protein moiety and lipoprotein binding to the cell surface are not affected by 5.0 mM of CPIB. CPIB lowers the incorporation of 14C-acetate, 14C-pyruvate, and 32phosphate radioactivity into fatty acids and phospholipids of aortic SMC. Five mM of CPIB reduce the overall palmitic acid synthesis by shifting from de novo synthesis to the mechanism of chain elongation, although the further elongation to saturated C18-C24 fatty acids is also depressed. The CPIB-enhanced retention of the lipid-derived lipoprotein radio-activity is interpreted as a compensatory mechanism providing cellular fatty acids which are deficient as a result of the CPIB inhibited synthetic processes.", "contents": "p-Chlorophenoxyisobutyrate enhanced retention of homologous lipoproteins by human aortic smooth muscle cells. Human aortic smooth muscle cells (SMC) specifically bind and take up indiscriminately both the lipid and protein moieties of homologous 25I-very low density lipoproteins (VLDL) and 125I-low density lipoproteins LDL). Sixty-five to 80% of absorbed lipids are incorporated into the cell lipids, preferentially into the phospholipid fraction. Twenty to 35% of the lipid bound and the protein moiety are eliminated from the cells. Half of the eliminated protein label is recovered as TCA soluble products. Five mM of p-chlorophenoxyisobutyrate (CPIB) raise the level of intracellular radioactivity derived from the lipid moieties of VLDL and LDL by about 40% via a reduced elimination. The processing of the protein moiety and lipoprotein binding to the cell surface are not affected by 5.0 mM of CPIB. CPIB lowers the incorporation of 14C-acetate, 14C-pyruvate, and 32phosphate radioactivity into fatty acids and phospholipids of aortic SMC. Five mM of CPIB reduce the overall palmitic acid synthesis by shifting from de novo synthesis to the mechanism of chain elongation, although the further elongation to saturated C18-C24 fatty acids is also depressed. The CPIB-enhanced retention of the lipid-derived lipoprotein radio-activity is interpreted as a compensatory mechanism providing cellular fatty acids which are deficient as a result of the CPIB inhibited synthetic processes."}
{"id": "PMID:201819", "title": "Effects of dibutyryl adenosine 3',5'-monophosphate on hepatic metabolism of free fatty acids.", "content": "The effects of dibutyryl cyclic adenosine 3',5'-monophosphate (Bu2cAMP) on metabolism of free fatty acids by perfused livers from normal fed male rats were investigated. In one group of experiments, Bu2cAMP was added to the medium and infused at a constant rate to maintain concentrations of 0, 0.4, 1.0, 4.0, or 10. 0 X 10(-5) M nucleotide in the perfusate plasma, assuming the nucleotide was not metabolized by the liver. Oleic acid was infused as the complex with albumin at the rate of 124.3 mumoles/hr. Uptake of free fatty acid by the liver was identical in all groups. Production of ketone bodies, however, increased, and output of triglyceride decreased with increasing concentration of Bu2cAMP. The nucleotide also stimulated output of glucose. Maximal effects were observed when the concentration of Bu2cAMP was approximately 2-3 X 10(-5) M. The output of very low density lipoproteins, as judged by flotation in the zonal ultracentrifuge, was also diminshed by the nucleotide. In other experiments, 1-14C-oleate was infused (120.8 mumoles/hr) along with 2 X 10(-5) M Bu2cAMP, and the disposition of 14C into CO2, ketone bodies, and esterified lipids was evaluated. Bu2cAMP depressed the proportion of 1-14C-oleate converted to triglyceride and increased the fraction converted to ketone bodies and CO2. Not only was ketogenesis stimulated, but a larger proportion of the ketone bodies was derived from exogenous fatty acid.", "contents": "Effects of dibutyryl adenosine 3',5'-monophosphate on hepatic metabolism of free fatty acids. The effects of dibutyryl cyclic adenosine 3',5'-monophosphate (Bu2cAMP) on metabolism of free fatty acids by perfused livers from normal fed male rats were investigated. In one group of experiments, Bu2cAMP was added to the medium and infused at a constant rate to maintain concentrations of 0, 0.4, 1.0, 4.0, or 10. 0 X 10(-5) M nucleotide in the perfusate plasma, assuming the nucleotide was not metabolized by the liver. Oleic acid was infused as the complex with albumin at the rate of 124.3 mumoles/hr. Uptake of free fatty acid by the liver was identical in all groups. Production of ketone bodies, however, increased, and output of triglyceride decreased with increasing concentration of Bu2cAMP. The nucleotide also stimulated output of glucose. Maximal effects were observed when the concentration of Bu2cAMP was approximately 2-3 X 10(-5) M. The output of very low density lipoproteins, as judged by flotation in the zonal ultracentrifuge, was also diminshed by the nucleotide. In other experiments, 1-14C-oleate was infused (120.8 mumoles/hr) along with 2 X 10(-5) M Bu2cAMP, and the disposition of 14C into CO2, ketone bodies, and esterified lipids was evaluated. Bu2cAMP depressed the proportion of 1-14C-oleate converted to triglyceride and increased the fraction converted to ketone bodies and CO2. Not only was ketogenesis stimulated, but a larger proportion of the ketone bodies was derived from exogenous fatty acid."}
{"id": "PMID:201820", "title": "Secondary type II hyperlipoproteinemia in patients with anorexia nervosa.", "content": "In 18 patients with anorexia nervosa, plasma cholesterol and triglyceride concentral concentrations were repeatedly determined over a period of 14 mo. In 11 patients elevated cholesterol concentrations were found which were due to an increase of low-density lipoprotein cholesterol, whereas high-density lipoprotein and very low density lipoprotein cholesterol levels were in the normal range. The elevated cholesterol values did not correlate with clinical and laboratory parameters such as the degree of weight loss and thyroid function tests. In follow-up studies it could be shown that in patients who regained their original weight, elevated plasma cholesterol concentrations fell to normal levels parallel to weight increase. In patients who showed no change in weight, however, cholesterol levels remained high. The cause for this secondary type II hyperlipoproteinemia in anorexia nervosa is not known. Hepatic triglyceride lipase and lipoprotein lipase activities in post-heparin plasma were found to be low despite normal triglyceride concentrations.", "contents": "Secondary type II hyperlipoproteinemia in patients with anorexia nervosa. In 18 patients with anorexia nervosa, plasma cholesterol and triglyceride concentral concentrations were repeatedly determined over a period of 14 mo. In 11 patients elevated cholesterol concentrations were found which were due to an increase of low-density lipoprotein cholesterol, whereas high-density lipoprotein and very low density lipoprotein cholesterol levels were in the normal range. The elevated cholesterol values did not correlate with clinical and laboratory parameters such as the degree of weight loss and thyroid function tests. In follow-up studies it could be shown that in patients who regained their original weight, elevated plasma cholesterol concentrations fell to normal levels parallel to weight increase. In patients who showed no change in weight, however, cholesterol levels remained high. The cause for this secondary type II hyperlipoproteinemia in anorexia nervosa is not known. Hepatic triglyceride lipase and lipoprotein lipase activities in post-heparin plasma were found to be low despite normal triglyceride concentrations."}
{"id": "PMID:201821", "title": "Effects of chlorinated hydrocarbon on plasma alpha-lipoprotein cholesterol in rats.", "content": "Ten chlorinated hydrocarbons (tetradifon, Chlorobenzilate, Kepone, lindane, Kelthane, toxaphene, dieldrin, hexachlorobenzene, dienochlor, and Aroclor 1254; see below) were evaluated in rats to assess agents which might selectively elevate high-density lipoprotein cholesterol (C-HDL). Single, nontoxic doses of Aroclor, dieldrin, and Kepone elevated C-HDL at day 7 (31%, 26%, and 24%, respectively, p less than 0.05). The C-HDL elevations were maintained at days 21 and 60 (28% and 31%, p less than 0.01) in the Aroclor group, while C-HDL returned to baseline in the dieldrin and Kepone groups. Liver function tests were unchanged from control, suggesting that the changes in C-HDL were not the consequence of hepatotoxicity. The hepatic microsomal cytochrome P-450 content of animals receiving Aroclor, dieldrin, and Kepone was 67%, 56%, and 44% higher than control values (p less than 0.02), indicating probable hepatic enzyme induction. If HDL (an antiatherogenic lipoprotein) is also selectively elevated by chlorinated hydrocarbons in man, then analogues might potentially be developed as antiatherogenic pharmacologic agents. Alternatively, the implications of man's exposure to halogenated hydrocarbons may be better understood.", "contents": "Effects of chlorinated hydrocarbon on plasma alpha-lipoprotein cholesterol in rats. Ten chlorinated hydrocarbons (tetradifon, Chlorobenzilate, Kepone, lindane, Kelthane, toxaphene, dieldrin, hexachlorobenzene, dienochlor, and Aroclor 1254; see below) were evaluated in rats to assess agents which might selectively elevate high-density lipoprotein cholesterol (C-HDL). Single, nontoxic doses of Aroclor, dieldrin, and Kepone elevated C-HDL at day 7 (31%, 26%, and 24%, respectively, p less than 0.05). The C-HDL elevations were maintained at days 21 and 60 (28% and 31%, p less than 0.01) in the Aroclor group, while C-HDL returned to baseline in the dieldrin and Kepone groups. Liver function tests were unchanged from control, suggesting that the changes in C-HDL were not the consequence of hepatotoxicity. The hepatic microsomal cytochrome P-450 content of animals receiving Aroclor, dieldrin, and Kepone was 67%, 56%, and 44% higher than control values (p less than 0.02), indicating probable hepatic enzyme induction. If HDL (an antiatherogenic lipoprotein) is also selectively elevated by chlorinated hydrocarbons in man, then analogues might potentially be developed as antiatherogenic pharmacologic agents. Alternatively, the implications of man's exposure to halogenated hydrocarbons may be better understood."}
{"id": "PMID:201822", "title": "A simple and efficient microassay method for titration of interferon.", "content": "A simple and efficient microassay method for the titration of interferon was developed by the use of microtest plates for handling a large number of samples. L929 cells pretreated with interferon were infected with vesicular stomatitis virus (VSV) and cultured in the presence of 3H-uridine. The activity was expressed by the reduction of extracellular radioactive RNA released after destruction of the infected cells, which was measured in terms of the radioactivity incorporated into cold TCA-insoluble materials in the culture fluid. The interferon titer determined by this method was in the same order as that by the plaque reduction method. The activity by this method was parallel to, but lower than that expressed by the yield reduction of infectious viruses. This method requires only 0.025 ml of each test sample with higher than 1 NIH ref. unit/ml to detect its interferon activity and takes 2 to 3 days for assaying hundreds of samples.", "contents": "A simple and efficient microassay method for titration of interferon. A simple and efficient microassay method for the titration of interferon was developed by the use of microtest plates for handling a large number of samples. L929 cells pretreated with interferon were infected with vesicular stomatitis virus (VSV) and cultured in the presence of 3H-uridine. The activity was expressed by the reduction of extracellular radioactive RNA released after destruction of the infected cells, which was measured in terms of the radioactivity incorporated into cold TCA-insoluble materials in the culture fluid. The interferon titer determined by this method was in the same order as that by the plaque reduction method. The activity by this method was parallel to, but lower than that expressed by the yield reduction of infectious viruses. This method requires only 0.025 ml of each test sample with higher than 1 NIH ref. unit/ml to detect its interferon activity and takes 2 to 3 days for assaying hundreds of samples."}
{"id": "PMID:201823", "title": "The relationships between cyclic AMP, calcium and prostaglandins as second messengers.", "content": "There is considerable dissatisfaction with present second messenger hypotheses involving cyclic nucleotides and calcium. The recent findings that methyl xanthines and adenosine are prostaglandin antagonists casts doubt on much of the evidence in favour of the cyclic AMP hypothesis. There is evidence that allosteric sites may modify the binding of calcium and cyclic nucleotides to key cellular regulators and that a range of substances including steroids, adenosine and prostaglandins may occupy those sites. This concept introduces much needed flexibility into the second messenger concept, allows many experiments to be reinterpreted and has major implications throughout the biomedical sciences.", "contents": "The relationships between cyclic AMP, calcium and prostaglandins as second messengers. There is considerable dissatisfaction with present second messenger hypotheses involving cyclic nucleotides and calcium. The recent findings that methyl xanthines and adenosine are prostaglandin antagonists casts doubt on much of the evidence in favour of the cyclic AMP hypothesis. There is evidence that allosteric sites may modify the binding of calcium and cyclic nucleotides to key cellular regulators and that a range of substances including steroids, adenosine and prostaglandins may occupy those sites. This concept introduces much needed flexibility into the second messenger concept, allows many experiments to be reinterpreted and has major implications throughout the biomedical sciences."}
{"id": "PMID:201835", "title": "[Cogenital goiter in a premature infant after amniography (author's transl)].", "content": "A premature infant was born with goiter and hypothyroidism 3 weeks after amniography. The correlation between excessive iodide exposure and thyroid function of discussed. The danger of using of idodine containing contrast media for amniography are emphasized.", "contents": "[Cogenital goiter in a premature infant after amniography (author's transl)]. A premature infant was born with goiter and hypothyroidism 3 weeks after amniography. The correlation between excessive iodide exposure and thyroid function of discussed. The danger of using of idodine containing contrast media for amniography are emphasized."}
{"id": "PMID:201843", "title": "Increased growth after long-term oral 1alpha,25-vitamin D3 in childhood renal osteodystrophy.", "content": "We evaluated oral 1,25-vitamin D3 for as long as 26 months in six prepubescent children with renal osteodystrophy previously treated with vitamin D2. Therapy was given at 14 to 41 ng per kilogram per day to correct hypocalcemia and reverse bone disease. Serum levels of 1,25-vitamin D3 were initially reduced at 15 +/- 5 pg per milliliter (mean +/- S.E.M.) and after treatment rose to 54 +/- 13. Serum calcium rose from 7.5 +/- 1.6 mg per deciliter (mean +/- S.D.) to 9.8 +/- 0.6 after one month (P less than 0.02). Alkaline phosphatase activity fell from 536 +/- 298 to 208 +/- 91 IU per liter after 12 months (P less than 0.05). Serum immunoreactive parathyroid levels fell from 900 +/- 562 microliter eq per milliliter 411 +/- 377. Healing of rickets and subperiosteal erosions was found. Remineralization of bone was demonstrated by the photon absorption technic. In four patients growth velocity, evaluated for 12 months before and after therapy, increased from 2.6 +/- 0.8 to 8.0 +/- 3.2 cm per year. Growth velocity per year increased from less than third percentile in each to the 10th to 97th percentile after therapy. Height increment ranged from 27 to 113 per cent of that expected for change in chronologic age and 40 to 114 per cent expected for change in bone age after therapy. This trial demonstrates that oral 1,25-vitamin D3 can reverse renal bone disease and increase growth in uremic children.", "contents": "Increased growth after long-term oral 1alpha,25-vitamin D3 in childhood renal osteodystrophy. We evaluated oral 1,25-vitamin D3 for as long as 26 months in six prepubescent children with renal osteodystrophy previously treated with vitamin D2. Therapy was given at 14 to 41 ng per kilogram per day to correct hypocalcemia and reverse bone disease. Serum levels of 1,25-vitamin D3 were initially reduced at 15 +/- 5 pg per milliliter (mean +/- S.E.M.) and after treatment rose to 54 +/- 13. Serum calcium rose from 7.5 +/- 1.6 mg per deciliter (mean +/- S.D.) to 9.8 +/- 0.6 after one month (P less than 0.02). Alkaline phosphatase activity fell from 536 +/- 298 to 208 +/- 91 IU per liter after 12 months (P less than 0.05). Serum immunoreactive parathyroid levels fell from 900 +/- 562 microliter eq per milliliter 411 +/- 377. Healing of rickets and subperiosteal erosions was found. Remineralization of bone was demonstrated by the photon absorption technic. In four patients growth velocity, evaluated for 12 months before and after therapy, increased from 2.6 +/- 0.8 to 8.0 +/- 3.2 cm per year. Growth velocity per year increased from less than third percentile in each to the 10th to 97th percentile after therapy. Height increment ranged from 27 to 113 per cent of that expected for change in chronologic age and 40 to 114 per cent expected for change in bone age after therapy. This trial demonstrates that oral 1,25-vitamin D3 can reverse renal bone disease and increase growth in uremic children."}
{"id": "PMID:201845", "title": "Protein-DNA and protein-hormone interactions in prealbumin: a model of the thyroid hormone nuclear receptor?", "content": "High resolution X-ray analysis of the hormone-binding protein prealbumin has shown that it has a structural complementarity to double-helical DNA. The proposed binding site is composed of two symmetry-related beta-sheets containing a pair of helically disposed arms, which can interact with the bases in the wide groove of DNA. A palindromic target sequence is indicated by the symmetry of the protein. The two identical thyroid hormone binding sites on prealbumin are located in a channel that runs completely through the molecule. These two structural features suggest prealbumin as a model for the thyroid hormone nuclear receptor, providing a number of detailed predictions of its properties.", "contents": "Protein-DNA and protein-hormone interactions in prealbumin: a model of the thyroid hormone nuclear receptor? High resolution X-ray analysis of the hormone-binding protein prealbumin has shown that it has a structural complementarity to double-helical DNA. The proposed binding site is composed of two symmetry-related beta-sheets containing a pair of helically disposed arms, which can interact with the bases in the wide groove of DNA. A palindromic target sequence is indicated by the symmetry of the protein. The two identical thyroid hormone binding sites on prealbumin are located in a channel that runs completely through the molecule. These two structural features suggest prealbumin as a model for the thyroid hormone nuclear receptor, providing a number of detailed predictions of its properties."}
{"id": "PMID:201850", "title": "Possible regulatory function of acetylcholine receptor in maintenance of retinotectal synapses.", "content": "alpha-Neurotoxins bind to cholinergic receptor, block transmission, and induce sprouting of retinal terminals in the toad tectum. New connections retain an orderliness that suggests a selective affinity between presynaptic terminals. The results suggest that postsynaptic cells exert a control, associated with receptors, on the growth of presynaptic terminals and on the maintenance of their synaptic connections.", "contents": "Possible regulatory function of acetylcholine receptor in maintenance of retinotectal synapses. alpha-Neurotoxins bind to cholinergic receptor, block transmission, and induce sprouting of retinal terminals in the toad tectum. New connections retain an orderliness that suggests a selective affinity between presynaptic terminals. The results suggest that postsynaptic cells exert a control, associated with receptors, on the growth of presynaptic terminals and on the maintenance of their synaptic connections."}
{"id": "PMID:201853", "title": "Recent excitement in the DNA replication problem.", "content": "It is now possible to reproduce most of the reactions involved in DNA replication using prokaryotic enzymes in vitro. Such systems have revealed that DNA replication is a complex process depending on a relatively large number of proteins, and that nucleoside triphosphate hydrolysis energy is used at several discrete steps. Much of the complexity of DNA replication may arise from the need for extreme copying fidelity.", "contents": "Recent excitement in the DNA replication problem. It is now possible to reproduce most of the reactions involved in DNA replication using prokaryotic enzymes in vitro. Such systems have revealed that DNA replication is a complex process depending on a relatively large number of proteins, and that nucleoside triphosphate hydrolysis energy is used at several discrete steps. Much of the complexity of DNA replication may arise from the need for extreme copying fidelity."}
{"id": "PMID:201867", "title": "A mutation that impairs the ability of lipoprotein receptors to localise in coated pits on the cell surface of human fibroblasts.", "content": "Low density lipoprotein is taken up by cultured human fibroblasts through an endocytic process that requires the binding of the lipoprotein to specific receptors located in coated pits on the cell surface. The coated pits are discrete segments of the plasms membrane that can undergo rapid invagination to form coated endocytic vesicles. In one form of the human genetic disorder familial hypercholesterolaemia, the responsible mutation produces altered lipoprotein receptors that lack the ability to become incorporated into coated pits. Instead, these mutant receptors are scattered at random over the entire plasma membrane. Becuase of their mislocation on the cell surface, the mutant lipoprotein receptors are unable to carry their bound lipoprotein into the cell. The occurrence of this 'receptor mislocation mutation' provides strong evidence for the role of the coated pit in the receptor-mediated uptake of lipoproteins. The data also have implications for the structure and assembly of plasma membranes in mammalian cells.", "contents": "A mutation that impairs the ability of lipoprotein receptors to localise in coated pits on the cell surface of human fibroblasts. Low density lipoprotein is taken up by cultured human fibroblasts through an endocytic process that requires the binding of the lipoprotein to specific receptors located in coated pits on the cell surface. The coated pits are discrete segments of the plasms membrane that can undergo rapid invagination to form coated endocytic vesicles. In one form of the human genetic disorder familial hypercholesterolaemia, the responsible mutation produces altered lipoprotein receptors that lack the ability to become incorporated into coated pits. Instead, these mutant receptors are scattered at random over the entire plasma membrane. Becuase of their mislocation on the cell surface, the mutant lipoprotein receptors are unable to carry their bound lipoprotein into the cell. The occurrence of this 'receptor mislocation mutation' provides strong evidence for the role of the coated pit in the receptor-mediated uptake of lipoproteins. The data also have implications for the structure and assembly of plasma membranes in mammalian cells."}
{"id": "PMID:201873", "title": "[EPSP's of the motor neurons of cat masticatory muscles induced by stimulation of low-threshold infraorbital nerve fibers].", "content": "The effects of the infraorbital Aalpha afferents stimulation on the masseter motoneurons were investigated in cats under chloralose-nembutal anesthesia. It is found that stimuli 1.4-2.5 times threshold (T) evoke complex EPSPs in 69% of the investigated motoneurons, their latency being 2.1 +/- 0.2 ms (1.5-3.0 ms, n = 36), amplitude up to 30 mV and duration 9-15 ms. These EPSPs consist of two simpler responses produced by activation of two separate groups of afferent fibres. The short-latent EPSPs arise after activation of the infraorbital nerve by 1.1-1.5 T stimuli and have the same latency as the complex EPSP (1.5-3.0 ms) but a smaller amplitude (up to 2.0 mV) and shorter duration (up to 6 ms). The stability of these EPSPs during high frequency stimulation (120/c) and the development of facilitation and inhibition similar to those which appear in monosynaptic EPSPs in masseter motoneurons during stimulation of the 1a muscle afferents give reason to suggest that these EPSPs are monosynaptic. The slow rising rate indicates that they appear on distal dendrites of the motoneurons. The long-latent EPSPs arise with latency of 7-9 ms after activation of the infraorbital nerve by 1.1-1.5 T stimuli. Their amplitude reaches 1.5-2.0 mV and duration 7-9 ms. The long latency of these EPSPs in combination with low ability to repeat high frequency stimulation are consistent with their polysynaptic origin. It is suggested that the excitatory input from the lowest threshold Aalpha afferents of the infraorbital nerve to masseter motoneurons creates conditions for the development of a transient jaw closing reflex in response to light tactile stimulation of the cat's perioral region.", "contents": "[EPSP's of the motor neurons of cat masticatory muscles induced by stimulation of low-threshold infraorbital nerve fibers]. The effects of the infraorbital Aalpha afferents stimulation on the masseter motoneurons were investigated in cats under chloralose-nembutal anesthesia. It is found that stimuli 1.4-2.5 times threshold (T) evoke complex EPSPs in 69% of the investigated motoneurons, their latency being 2.1 +/- 0.2 ms (1.5-3.0 ms, n = 36), amplitude up to 30 mV and duration 9-15 ms. These EPSPs consist of two simpler responses produced by activation of two separate groups of afferent fibres. The short-latent EPSPs arise after activation of the infraorbital nerve by 1.1-1.5 T stimuli and have the same latency as the complex EPSP (1.5-3.0 ms) but a smaller amplitude (up to 2.0 mV) and shorter duration (up to 6 ms). The stability of these EPSPs during high frequency stimulation (120/c) and the development of facilitation and inhibition similar to those which appear in monosynaptic EPSPs in masseter motoneurons during stimulation of the 1a muscle afferents give reason to suggest that these EPSPs are monosynaptic. The slow rising rate indicates that they appear on distal dendrites of the motoneurons. The long-latent EPSPs arise with latency of 7-9 ms after activation of the infraorbital nerve by 1.1-1.5 T stimuli. Their amplitude reaches 1.5-2.0 mV and duration 7-9 ms. The long latency of these EPSPs in combination with low ability to repeat high frequency stimulation are consistent with their polysynaptic origin. It is suggested that the excitatory input from the lowest threshold Aalpha afferents of the infraorbital nerve to masseter motoneurons creates conditions for the development of a transient jaw closing reflex in response to light tactile stimulation of the cat's perioral region."}
{"id": "PMID:201874", "title": "Cyclophosphamide induced sensitivity against avian RNA myeloblastosis virus in age-resistant hosts.", "content": "The effect of cyclophosphamide administration on survival of 4- to 7-week-old chickens as well as on induction of leukemia after avian myeloblastosis virus (AMV) injection was studied. The drug treatment alone did not cause any neoplastic effect in the birds during 4 months of observation. Immediate application of AMV to cyclophosphamide-pretreated age-resistant chickens induced acute myeloblastic leukemia in about 80 per cent of test animals. The sensitivity of chickens against AMV, induced by cyclophosphamide, had transient character only. When AMV was injected delayed, 3 or 10 days later, after the administration of the drug was completed, a rapid and pronounced increase of resistance was observed again.", "contents": "Cyclophosphamide induced sensitivity against avian RNA myeloblastosis virus in age-resistant hosts. The effect of cyclophosphamide administration on survival of 4- to 7-week-old chickens as well as on induction of leukemia after avian myeloblastosis virus (AMV) injection was studied. The drug treatment alone did not cause any neoplastic effect in the birds during 4 months of observation. Immediate application of AMV to cyclophosphamide-pretreated age-resistant chickens induced acute myeloblastic leukemia in about 80 per cent of test animals. The sensitivity of chickens against AMV, induced by cyclophosphamide, had transient character only. When AMV was injected delayed, 3 or 10 days later, after the administration of the drug was completed, a rapid and pronounced increase of resistance was observed again."}
{"id": "PMID:201875", "title": "Biochemical properties of endogenous rat C-type viruses.", "content": "The cellular restriction to persistence of inducible C-type viruses of at least two rat strains can be overcome in actively in vitro replicating and/or spontaneously transforming rat embryo cells. Both, SD-RaLV and W-RaLV particles are morphologically and biochemically related to known oncorna viruses: They are of C-type, have an identical buoyant density of 1.15 g/cm3 in sucrose gradients and contain high-molecular-weight RNA. The RaLV-associated DNA polymerase exhibit both exogenous (polynucleotide-templated) and endogenous (viral RNA-templated) reactivity. The enzyme strongly preferred Mn++ over Mg++ ions (Mg++/Mn++ ratio of 0.04 to 0.07), with maximum reactivity at 0.1 mM MnCl2 concentration. The molecular hybridization experiments revealed the endogenous nature of the SD-RaLV and the W-RaLV. From the competition hybridization assay the number of proviral sequences could be calculated to be 84 per haploid cell genome. The role of endogenous rat viruses in the \"spontaneous\" in vitro transformation is discussed.", "contents": "Biochemical properties of endogenous rat C-type viruses. The cellular restriction to persistence of inducible C-type viruses of at least two rat strains can be overcome in actively in vitro replicating and/or spontaneously transforming rat embryo cells. Both, SD-RaLV and W-RaLV particles are morphologically and biochemically related to known oncorna viruses: They are of C-type, have an identical buoyant density of 1.15 g/cm3 in sucrose gradients and contain high-molecular-weight RNA. The RaLV-associated DNA polymerase exhibit both exogenous (polynucleotide-templated) and endogenous (viral RNA-templated) reactivity. The enzyme strongly preferred Mn++ over Mg++ ions (Mg++/Mn++ ratio of 0.04 to 0.07), with maximum reactivity at 0.1 mM MnCl2 concentration. The molecular hybridization experiments revealed the endogenous nature of the SD-RaLV and the W-RaLV. From the competition hybridization assay the number of proviral sequences could be calculated to be 84 per haploid cell genome. The role of endogenous rat viruses in the \"spontaneous\" in vitro transformation is discussed."}
{"id": "PMID:201877", "title": "Mitochondrial adenosine triphosphatase of Zajdela hepatoma. III. Effect of uncouplers on the hydrolysis of intramitochondrial ATP.", "content": "Hydrolysis of extramitochondrial ATP by coupled Zajdela hepatoma mitochondria is not stimulated by uncouplers of oxidative phosphorylation. The results of the present study show that the hydrolysis of intramitochondrial ATP in these mitochondria is stimulated by DNP and CCCP. It is proposed that the uncoupler insensitivity of ATPase in coupled Zajdela hepatoma mitochondria with exogenous ATP as a substrate result from an altered functional relationship between ATPase and ADP, ATP translocase.", "contents": "Mitochondrial adenosine triphosphatase of Zajdela hepatoma. III. Effect of uncouplers on the hydrolysis of intramitochondrial ATP. Hydrolysis of extramitochondrial ATP by coupled Zajdela hepatoma mitochondria is not stimulated by uncouplers of oxidative phosphorylation. The results of the present study show that the hydrolysis of intramitochondrial ATP in these mitochondria is stimulated by DNP and CCCP. It is proposed that the uncoupler insensitivity of ATPase in coupled Zajdela hepatoma mitochondria with exogenous ATP as a substrate result from an altered functional relationship between ATPase and ADP, ATP translocase."}
{"id": "PMID:201881", "title": "Pars intermedia ACTH and MSH content: effect of adrenalectomy, gonadectomy and a neurotropic (noise) stress.", "content": "Pars intermedia (PI) ACTH and melanocyte-stimulating hormone (MSH) content and pars distalis (PD) ACTH concentration were measured following 3 experimentally induced 'perturbations'. The feedback-induced increase in ACTH release following adrenalectomy is not accompanied by a change in PI ACTH and MSH contents, while the feedback-induced increase in gonadotropin secretion following gonadectomy is associated with significant changes in PI ACTH and MSH contents. A well-defined neurotropic (noise) stressor resulted in significant increases in PI ACTH and MSH. A striking finding in all of the studies was a positive correlation between PI ACTH and MSH contents. We conclude that PI ACTH and MSH secretion are altered with feedback-induced alterations in gonadotropin secretion and with neurotropic stressors.", "contents": "Pars intermedia ACTH and MSH content: effect of adrenalectomy, gonadectomy and a neurotropic (noise) stress. Pars intermedia (PI) ACTH and melanocyte-stimulating hormone (MSH) content and pars distalis (PD) ACTH concentration were measured following 3 experimentally induced 'perturbations'. The feedback-induced increase in ACTH release following adrenalectomy is not accompanied by a change in PI ACTH and MSH contents, while the feedback-induced increase in gonadotropin secretion following gonadectomy is associated with significant changes in PI ACTH and MSH contents. A well-defined neurotropic (noise) stressor resulted in significant increases in PI ACTH and MSH. A striking finding in all of the studies was a positive correlation between PI ACTH and MSH contents. We conclude that PI ACTH and MSH secretion are altered with feedback-induced alterations in gonadotropin secretion and with neurotropic stressors."}
{"id": "PMID:201879", "title": "[Effect of polysynaptic flexion reflex on monosynaptic reflexes of calf muscles prior to and following intramuscular injection of ethylbenzatropine in drug-induced muscle rigidity].", "content": "In patients with drug-induced parkinsonism and in healthy subjects the effect of stimulation of low-threshold skin fibres of sural nerve producing the polysynaptic flexion reflex of the short head of the biceps femoris muscle on the monosynaptic H reflex of calf muscles was studied before and after administration of ethylbenzatropine. In healthy subjects stimulation of low-threshold skin nerve was followed by facilitation of H reflex in the time of 70 to 200 msec. from the conditioning stimulation to the test stimulation. After one single intramuscular dose of ethylbenzatropine this late facilitating effect disappeared. In patients with drug-induced parkinsonism stimulation of afferent fibres of flexion reflex failed to cause late facilitation of H reflex and one dose of ethylbenzatropine brought no changes. During systematic administration of the drug an evident tendency for facilitation of H reflex was observed, similarly as in healthy subjects. The results obtained in healthy subjects and in patients with drug-induced parkinsonism are explained as evidence of inhibitory action of noradrenaline in certain chains of spinal interneurons, since noradrenaline release in the spinal cord is determined by the striatal equilibrium between the cholinergic and dopaminergic systems. The corrective action of ethylbenzatropine would depend on its central action on certain spinal chains of interneurons determining transmission of impulses from dermal afferent nerves to alpha motoneurons.", "contents": "[Effect of polysynaptic flexion reflex on monosynaptic reflexes of calf muscles prior to and following intramuscular injection of ethylbenzatropine in drug-induced muscle rigidity]. In patients with drug-induced parkinsonism and in healthy subjects the effect of stimulation of low-threshold skin fibres of sural nerve producing the polysynaptic flexion reflex of the short head of the biceps femoris muscle on the monosynaptic H reflex of calf muscles was studied before and after administration of ethylbenzatropine. In healthy subjects stimulation of low-threshold skin nerve was followed by facilitation of H reflex in the time of 70 to 200 msec. from the conditioning stimulation to the test stimulation. After one single intramuscular dose of ethylbenzatropine this late facilitating effect disappeared. In patients with drug-induced parkinsonism stimulation of afferent fibres of flexion reflex failed to cause late facilitation of H reflex and one dose of ethylbenzatropine brought no changes. During systematic administration of the drug an evident tendency for facilitation of H reflex was observed, similarly as in healthy subjects. The results obtained in healthy subjects and in patients with drug-induced parkinsonism are explained as evidence of inhibitory action of noradrenaline in certain chains of spinal interneurons, since noradrenaline release in the spinal cord is determined by the striatal equilibrium between the cholinergic and dopaminergic systems. The corrective action of ethylbenzatropine would depend on its central action on certain spinal chains of interneurons determining transmission of impulses from dermal afferent nerves to alpha motoneurons."}
{"id": "PMID:201880", "title": "[Comparison of results of polygraphic sleep studies and cerebrospinal fluid pressure records in patients following removal of supratentorial expanding lesions].", "content": "In 4 patients operated upon for supratentorial brain tumors the authors carried out on the 3rd day after the operation polygraphic recording of nocturnal sleep with simultaneous measurements of cerebrospinal fluid pressure in the ventricular system by the method of Lundberg. A comparison of polygraphic records of nocturnal sleep with parallel measurements of intraventricular pressure demonstrated that all REM phases were associated with a rise in intraventricular pressure, while during phases 3 and 4 of sleep (NREM) the intraventricular pressure was always lower. In the remaining sleep phases 1,2 NREM and during episodes of nocturnal awakening no unequivocal consistencies were found.", "contents": "[Comparison of results of polygraphic sleep studies and cerebrospinal fluid pressure records in patients following removal of supratentorial expanding lesions]. In 4 patients operated upon for supratentorial brain tumors the authors carried out on the 3rd day after the operation polygraphic recording of nocturnal sleep with simultaneous measurements of cerebrospinal fluid pressure in the ventricular system by the method of Lundberg. A comparison of polygraphic records of nocturnal sleep with parallel measurements of intraventricular pressure demonstrated that all REM phases were associated with a rise in intraventricular pressure, while during phases 3 and 4 of sleep (NREM) the intraventricular pressure was always lower. In the remaining sleep phases 1,2 NREM and during episodes of nocturnal awakening no unequivocal consistencies were found."}
{"id": "PMID:201886", "title": "Inclusion body myositis: a distinct variety of idiopathic inflammatory myopathy.", "content": "We report six cases of inclusion body myositis (IBM), a distinct but infrequently recognized inflammatory disease of skeletal muscle. Clinically, IBM differs from dermatomyositis and polymyositis. It lacks features of collagen-vascular disease, has a relatively benign and protracted course, frequently involves distal muscles, is found mainly in males, and does not improve with corticosteroid treatment. Electronmicroscopic demonstration of abnormal filaments in muscle cells is necessary for definite diagnosis, but IBM may be suspected by the finding on cryostat sections of numerous hematoxylinophilic granules in \"lined\" vacuoles in muscle cells. These correspond to whorls of cytomembranes. Although in dermatomyositis the capillary network is partly destroyed, in IBM it is usually augmented. A viral etiology of IBM has been suggested but remains unproven.", "contents": "Inclusion body myositis: a distinct variety of idiopathic inflammatory myopathy. We report six cases of inclusion body myositis (IBM), a distinct but infrequently recognized inflammatory disease of skeletal muscle. Clinically, IBM differs from dermatomyositis and polymyositis. It lacks features of collagen-vascular disease, has a relatively benign and protracted course, frequently involves distal muscles, is found mainly in males, and does not improve with corticosteroid treatment. Electronmicroscopic demonstration of abnormal filaments in muscle cells is necessary for definite diagnosis, but IBM may be suspected by the finding on cryostat sections of numerous hematoxylinophilic granules in \"lined\" vacuoles in muscle cells. These correspond to whorls of cytomembranes. Although in dermatomyositis the capillary network is partly destroyed, in IBM it is usually augmented. A viral etiology of IBM has been suggested but remains unproven."}
{"id": "PMID:201887", "title": "EEG frequency spectrum characteristics of sleep states in infants of alcoholic mothers.", "content": "Infants of alcoholic mothers showed prominent EEG hypersynchrony in all three stages of sleep: in quiet sleep, indeterminate sleep and active-REM sleep. Spectral analysis of the EEG using fast Fourier transform revealed significant increase in power in most frequency bands in all three stages of sleep in infants born to alcoholic mothers when compared with normal healthy infants matched for gestational age. In quiet sleep \"alcoholic\" infants differed from healthy babies by significantly higher power in a wide range of frequency bands (1.5--17.5 Hz) with an average 143% increase of the integrated EEG (1.5--25 Hz). In indeterminate sleep \"alcoholic\" infants showed significantly higher power in all analyzed frequency bands (0.1--25 Hz) with an average 196% increase of the integrated EEG (1.5--25 Hz). In active-REM sleep infants of alcoholic mothers showed significantly higher power in the frequency range from 0.1 to 17.5 Hz in comparison with healthy controls. The average increase of the integrated EEG (1.5--25 Hz) was 200%. All healthy term infants showed significantly higher power in most frequency bands during quiet sleep in comparison with active-REM sleep. In infants born to alcoholic mothers this quiet sleep--REM sleep frequency spectrum difference in the majority of cases was nonsignificant mainly due to high values of the EEG power during REM sleep. It is unlikely that the EEG hypersynchrony in infants of alcoholic mothers represents one of the symptoms of the neonatal alcohol-withdrawal syndrome since hypersynchrony has been detected as long as 6 weeks after birth. During this time any withdrawal symptoms would have been dissipated.", "contents": "EEG frequency spectrum characteristics of sleep states in infants of alcoholic mothers. Infants of alcoholic mothers showed prominent EEG hypersynchrony in all three stages of sleep: in quiet sleep, indeterminate sleep and active-REM sleep. Spectral analysis of the EEG using fast Fourier transform revealed significant increase in power in most frequency bands in all three stages of sleep in infants born to alcoholic mothers when compared with normal healthy infants matched for gestational age. In quiet sleep \"alcoholic\" infants differed from healthy babies by significantly higher power in a wide range of frequency bands (1.5--17.5 Hz) with an average 143% increase of the integrated EEG (1.5--25 Hz). In indeterminate sleep \"alcoholic\" infants showed significantly higher power in all analyzed frequency bands (0.1--25 Hz) with an average 196% increase of the integrated EEG (1.5--25 Hz). In active-REM sleep infants of alcoholic mothers showed significantly higher power in the frequency range from 0.1 to 17.5 Hz in comparison with healthy controls. The average increase of the integrated EEG (1.5--25 Hz) was 200%. All healthy term infants showed significantly higher power in most frequency bands during quiet sleep in comparison with active-REM sleep. In infants born to alcoholic mothers this quiet sleep--REM sleep frequency spectrum difference in the majority of cases was nonsignificant mainly due to high values of the EEG power during REM sleep. It is unlikely that the EEG hypersynchrony in infants of alcoholic mothers represents one of the symptoms of the neonatal alcohol-withdrawal syndrome since hypersynchrony has been detected as long as 6 weeks after birth. During this time any withdrawal symptoms would have been dissipated."}
{"id": "PMID:201889", "title": "[Endocrine aspects of puberty. Modifications of gonadotropins (LH, FSH), testosterone and cortisol circulating after ACTH and synthetic LH-RH].", "content": "The effect of synthetic LH-RH (Relisorm Serono: 25 microgram i.v.) on plasma LH, FSH and testosterone was examined in 19 normal pubescent and prepubescent boys. Changes in cortisol and testosterone after 0.25 mg/m2 body surface ACTH (Synacthen ciba) was assessed in a further 8 prepubescent subjects. Notable amounts of FSH, LH and testosterone were noted in prepubescent subjects, pointing to hormonal production prior to sexual maturation. There was a prompt and significant increase in LH in all cases. In prepubescent subjects, this was accompanied by marked increases in FSH on some occasions, though no appreciable change in circulating testosterone. This suggests that the hypophyseal reserve of LH is sufficient in puberty. Prepubescent subjects displayed a significant rise in cortisol 30' and 60' after ACTH, whereas testosterone fell with respect to the start values. The results indicate that acute stimulation of the adrenal cortex before puberty leads to testosterone suppression.", "contents": "[Endocrine aspects of puberty. Modifications of gonadotropins (LH, FSH), testosterone and cortisol circulating after ACTH and synthetic LH-RH]. The effect of synthetic LH-RH (Relisorm Serono: 25 microgram i.v.) on plasma LH, FSH and testosterone was examined in 19 normal pubescent and prepubescent boys. Changes in cortisol and testosterone after 0.25 mg/m2 body surface ACTH (Synacthen ciba) was assessed in a further 8 prepubescent subjects. Notable amounts of FSH, LH and testosterone were noted in prepubescent subjects, pointing to hormonal production prior to sexual maturation. There was a prompt and significant increase in LH in all cases. In prepubescent subjects, this was accompanied by marked increases in FSH on some occasions, though no appreciable change in circulating testosterone. This suggests that the hypophyseal reserve of LH is sufficient in puberty. Prepubescent subjects displayed a significant rise in cortisol 30' and 60' after ACTH, whereas testosterone fell with respect to the start values. The results indicate that acute stimulation of the adrenal cortex before puberty leads to testosterone suppression."}
{"id": "PMID:201890", "title": "Rat liver mitochondrial cytochrome c oxidase and cytochromes in experimental protein-energy malnutrition.", "content": "Cytochrome c oxidase activity and cytochromes b, (c+c1) and a(+a3) concentrations were determined in liver mitochondria from rats fed the following diets: controls (group 1) fed ad libitum, energy-restricted (group 2) and protein-deficient (group 3). The animals were fed for two time intervals, 3--5 and 7--9 weeks. At 3--5 weeks, the cytochrome oxidase specific activity (nmol cytochrome c oxidized/mg protein/min) and cytochrome concentrations (nmol/mg protein) were not different in groups 2 and 3 as compared to group 1. At 7--9 weeks, the cytochrome oxidase specific activity and concentrations of cytochromes b, (c+c1) and a(+a3) were significantly reduced in group 2 rats as compared to well-fed controls. The Michaelis-Menten constant, Km apparent for ferrocytochrome c, was significantly higher in group 2 as compared to group 1. In group 3 rats, cytochrome oxidase specific activity and cytochrome b, a(+a3) concentrations were not different from group 1 at 7-9 weeks. However, cytochrome (c+c1) concentration was higher in group 3, resulting in an elevated ratio of cytochrome (c+c1) to cytochrome a(+a3) as compared to groups 1 and 2.", "contents": "Rat liver mitochondrial cytochrome c oxidase and cytochromes in experimental protein-energy malnutrition. Cytochrome c oxidase activity and cytochromes b, (c+c1) and a(+a3) concentrations were determined in liver mitochondria from rats fed the following diets: controls (group 1) fed ad libitum, energy-restricted (group 2) and protein-deficient (group 3). The animals were fed for two time intervals, 3--5 and 7--9 weeks. At 3--5 weeks, the cytochrome oxidase specific activity (nmol cytochrome c oxidized/mg protein/min) and cytochrome concentrations (nmol/mg protein) were not different in groups 2 and 3 as compared to group 1. At 7--9 weeks, the cytochrome oxidase specific activity and concentrations of cytochromes b, (c+c1) and a(+a3) were significantly reduced in group 2 rats as compared to well-fed controls. The Michaelis-Menten constant, Km apparent for ferrocytochrome c, was significantly higher in group 2 as compared to group 1. In group 3 rats, cytochrome oxidase specific activity and cytochrome b, a(+a3) concentrations were not different from group 1 at 7-9 weeks. However, cytochrome (c+c1) concentration was higher in group 3, resulting in an elevated ratio of cytochrome (c+c1) to cytochrome a(+a3) as compared to groups 1 and 2."}
{"id": "PMID:201893", "title": "Methotrexate with citrovorum factor rescue for gestational trophoblastic neoplasms.", "content": "Thirty-five patients with nometastatic gestational trophoblastic neoplasms and 3 patients with metastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor rescue. The antecedent pregnancy was molar in all patients. The known histologic diagnosis in 34 patients was hydatdiform mole and choriocarcinoma in 3. Up to March 1977, the duration of remissions ranged from 1 to 21 months. Complete and sustained remission was achieved in 91% of patients with nonmetastatic disease and in 2 of the 3 patients with metastases, without evidence of marrow or hepatic and with substantially reduced epithelial toxicity. Response to treatment and the number of courses required to achieve remission were determined solely on the basis of the human chorionic gonadotropin response as measured by the beta subunit radioimmunoassay.", "contents": "Methotrexate with citrovorum factor rescue for gestational trophoblastic neoplasms. Thirty-five patients with nometastatic gestational trophoblastic neoplasms and 3 patients with metastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor rescue. The antecedent pregnancy was molar in all patients. The known histologic diagnosis in 34 patients was hydatdiform mole and choriocarcinoma in 3. Up to March 1977, the duration of remissions ranged from 1 to 21 months. Complete and sustained remission was achieved in 91% of patients with nonmetastatic disease and in 2 of the 3 patients with metastases, without evidence of marrow or hepatic and with substantially reduced epithelial toxicity. Response to treatment and the number of courses required to achieve remission were determined solely on the basis of the human chorionic gonadotropin response as measured by the beta subunit radioimmunoassay."}
{"id": "PMID:201895", "title": "Temperature effects on the modulation of adenylate cyclases from rat liver and Morris hepatomas.", "content": "When adenylate cyclase activities in purified membranes from normal rat liver and from a series of rapid growing transplantable Morris hepatomas were examined at various temperatures, several unique features were observed. Two of the hepatomas yielded patterns similar to that of normal liver, even though glucagon did not activate either tumor adenylate cyclase but did activate the normal liver enzyme. The patterns of the third tumor line were completely different from normal. This clearly shows the heterogeneity in cancers of similar origin.", "contents": "Temperature effects on the modulation of adenylate cyclases from rat liver and Morris hepatomas. When adenylate cyclase activities in purified membranes from normal rat liver and from a series of rapid growing transplantable Morris hepatomas were examined at various temperatures, several unique features were observed. Two of the hepatomas yielded patterns similar to that of normal liver, even though glucagon did not activate either tumor adenylate cyclase but did activate the normal liver enzyme. The patterns of the third tumor line were completely different from normal. This clearly shows the heterogeneity in cancers of similar origin."}
{"id": "PMID:201896", "title": "Adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate levels in human breast cancer tissue.", "content": "Intracellular levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate were measured in breast carcinomas. These levels were increased significantly as compared to normal breast tissues. In benign breast tumors, intermediate levels of adenosine 3'5'-cyclic monophosphate were observed, but they did not differ significantly with malignant tissues. No relation has been shown with estradiol or progesterone binding sites.", "contents": "Adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate levels in human breast cancer tissue. Intracellular levels of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate were measured in breast carcinomas. These levels were increased significantly as compared to normal breast tissues. In benign breast tumors, intermediate levels of adenosine 3'5'-cyclic monophosphate were observed, but they did not differ significantly with malignant tissues. No relation has been shown with estradiol or progesterone binding sites."}
{"id": "PMID:201898", "title": "An investigation into the relationship of the immunological status of Herpes simplex virus type-2 (HSV-2) infected animals and the tumor-enhancing property of this infection.", "content": "In order to compare the state of immunity of HSV-2 infected animals with their sham treated counterparts, several in vivo methods for cell-mediated immunity in addition to the stimulation in vitro of mouse splenocytes with PHA were performed. The grafting of C 3 H mice with heterologous skin and the paw test with PHA showed no noticeable difference between the two groups. The tuberculin test performed on guinea pigs infected via the footpads, permitted the detection of a slightly impaired reactivity of the virus-infected animals. The PHA assay in vitro showed reduced stimulation indices with cultures of splenocytes from virus-infected mice about 10 days p.i. These reduced stimulation indices are the result of 1. a low 3 HTdR incorporation by the PHA stimulated cultures and 2. of a relatively high 3 HTdR uptake by the unstimulated control cultures. An interpretation of these results is suggested. Finally, the possible implications of a shortlived impaired cell-mediated immunity on the tumour enhancing property of the HSV-2 infection, which has been described in previous publications, are discussed.", "contents": "An investigation into the relationship of the immunological status of Herpes simplex virus type-2 (HSV-2) infected animals and the tumor-enhancing property of this infection. In order to compare the state of immunity of HSV-2 infected animals with their sham treated counterparts, several in vivo methods for cell-mediated immunity in addition to the stimulation in vitro of mouse splenocytes with PHA were performed. The grafting of C 3 H mice with heterologous skin and the paw test with PHA showed no noticeable difference between the two groups. The tuberculin test performed on guinea pigs infected via the footpads, permitted the detection of a slightly impaired reactivity of the virus-infected animals. The PHA assay in vitro showed reduced stimulation indices with cultures of splenocytes from virus-infected mice about 10 days p.i. These reduced stimulation indices are the result of 1. a low 3 HTdR incorporation by the PHA stimulated cultures and 2. of a relatively high 3 HTdR uptake by the unstimulated control cultures. An interpretation of these results is suggested. Finally, the possible implications of a shortlived impaired cell-mediated immunity on the tumour enhancing property of the HSV-2 infection, which has been described in previous publications, are discussed."}
{"id": "PMID:201899", "title": "The phosphorylation of histones in herpes virus infected Vervet-monkey kidney cells (CV-1).", "content": "The phosphorylation of histones of the F1 group and of fraction F2a2 is stimulated in monkey kidney cells (CV-1) to almost two times the control values 14 hours after their infection with herpes virus, type 2. At the same time high amounts of viral DNA are produced. It seems very likely that the stimulated phosphorylation of these histone fractions is a prerequisite for the enhanced synthesis of DNA and possibly also RNA.", "contents": "The phosphorylation of histones in herpes virus infected Vervet-monkey kidney cells (CV-1). The phosphorylation of histones of the F1 group and of fraction F2a2 is stimulated in monkey kidney cells (CV-1) to almost two times the control values 14 hours after their infection with herpes virus, type 2. At the same time high amounts of viral DNA are produced. It seems very likely that the stimulated phosphorylation of these histone fractions is a prerequisite for the enhanced synthesis of DNA and possibly also RNA."}
{"id": "PMID:201901", "title": "Immediate endocrine and metabolic consequences of traumatic quadriplegia in a young woman.", "content": "Onset of paralysis by cervical spinal cord injury led immediately to temporary adrenocortical activation and, within 2 days, to sustained skin and bone breakdown. Urine cAMP was increased, blood parathyroid hormone, renin activity, and electrolytes were normal, and fluid and electrolytes balance became negative during the initial 6 days of paralysis.", "contents": "Immediate endocrine and metabolic consequences of traumatic quadriplegia in a young woman. Onset of paralysis by cervical spinal cord injury led immediately to temporary adrenocortical activation and, within 2 days, to sustained skin and bone breakdown. Urine cAMP was increased, blood parathyroid hormone, renin activity, and electrolytes were normal, and fluid and electrolytes balance became negative during the initial 6 days of paralysis."}
{"id": "PMID:201902", "title": "Intraspinal neoplasms in children.", "content": "Twenty-nine primary intraspinal neoplasms in children observed between 1936  and 1975 in Connecticut are reviewed. Most of them were gliomas: 45 per cent astrocytoma, 24 per cent ependymal neoplasm, 10 per cent glioblastoma multiforme and 7 per cent glioma. Symptoms, physical findings and therapy are reviewed.", "contents": "Intraspinal neoplasms in children. Twenty-nine primary intraspinal neoplasms in children observed between 1936  and 1975 in Connecticut are reviewed. Most of them were gliomas: 45 per cent astrocytoma, 24 per cent ependymal neoplasm, 10 per cent glioblastoma multiforme and 7 per cent glioma. Symptoms, physical findings and therapy are reviewed."}
{"id": "PMID:201906", "title": "[Evolution of cytomegalovirus antibodies of maternal origin and acquired, throughout the first year of life (author's transl)].", "content": "Cytomegalovirus antibodies have been determined by indirect hemagglutination technique in sera taken during the first year of life in two infant groups : Bantu infants in Mozambique, French infants in Alsace. IgM specific antibodies have been detected in serum fractions obtained by density gradients. The evolutions of maternal antibodies and of antibodies resulting from a primary CMV infection have been documented. The analysis of the results confirmed that the mother is the main source of infection and that contamination occurs at the time of birth.", "contents": "[Evolution of cytomegalovirus antibodies of maternal origin and acquired, throughout the first year of life (author's transl)]. Cytomegalovirus antibodies have been determined by indirect hemagglutination technique in sera taken during the first year of life in two infant groups : Bantu infants in Mozambique, French infants in Alsace. IgM specific antibodies have been detected in serum fractions obtained by density gradients. The evolutions of maternal antibodies and of antibodies resulting from a primary CMV infection have been documented. The analysis of the results confirmed that the mother is the main source of infection and that contamination occurs at the time of birth."}
{"id": "PMID:201907", "title": "Gold nephropathy.", "content": "Nephropathy with proteinuria is an occasional complication of gold therapy for rheumatoid arthritis and is considered to be due to an immune hypersensitivity reaction. Three patients are described in whom the structural changes typical of gold nephropathy were demonstrated by electron microscopy of renal biopsies. There was early membranous glomerular nephropathy with multiple sub-epithelial deposits of immune complexes. In one case these were shown by immunofluorescence to contain IgG and complement. Proximal tubules contained characteristic dense granular intracytoplasmic gold inclusions, best demonstrated by electron microscopy of unstained sections.", "contents": "Gold nephropathy. Nephropathy with proteinuria is an occasional complication of gold therapy for rheumatoid arthritis and is considered to be due to an immune hypersensitivity reaction. Three patients are described in whom the structural changes typical of gold nephropathy were demonstrated by electron microscopy of renal biopsies. There was early membranous glomerular nephropathy with multiple sub-epithelial deposits of immune complexes. In one case these were shown by immunofluorescence to contain IgG and complement. Proximal tubules contained characteristic dense granular intracytoplasmic gold inclusions, best demonstrated by electron microscopy of unstained sections."}
{"id": "PMID:201908", "title": "Cerebellar calcification: a possible marker of lead poisoning.", "content": "An unusual form of calcification in the cerebellum has been observed in routine autopsies in Queensland over the past 30 years. In 4 surveys carried out at intervals between 1951 and 1976 the lesion has been found microscopically in 10 to 15% of autopsies. There is a significant correlation between cerebellar calcification and raised lead levels in bone.", "contents": "Cerebellar calcification: a possible marker of lead poisoning. An unusual form of calcification in the cerebellum has been observed in routine autopsies in Queensland over the past 30 years. In 4 surveys carried out at intervals between 1951 and 1976 the lesion has been found microscopically in 10 to 15% of autopsies. There is a significant correlation between cerebellar calcification and raised lead levels in bone."}
{"id": "PMID:201909", "title": "The effect of cyclic AMP on human colony forming cell and colony stimulating factor production.", "content": "The effect of cyclic AMP (cAMP) and related nucleotides on human colony forming cells (CFC) and those cells producing colony stimulating factor (CSF) was studied in vitro. When added at physiological concentrations (10(-2) to 1 micron), exogenous cAMP stimulated maximum colony formation in cultures without feeder layers. Related nucleotides stimulated colony formation to a lesser extent and in decreasing order of free energy. All nucleotides inhibited colony formation in concentrations above 1 micron. A velocity sedimentation cell separation technique was used to obtain cell fractions rich in CFC but poor in CSF-producing cells. Such fractions did not respond to cAMP stimulation. These studies suggest that exogenous cAMP stimulates human bone marrow to form colonies in vitro by increasing the release and/or production of endogenous CSF.", "contents": "The effect of cyclic AMP on human colony forming cell and colony stimulating factor production. The effect of cyclic AMP (cAMP) and related nucleotides on human colony forming cells (CFC) and those cells producing colony stimulating factor (CSF) was studied in vitro. When added at physiological concentrations (10(-2) to 1 micron), exogenous cAMP stimulated maximum colony formation in cultures without feeder layers. Related nucleotides stimulated colony formation to a lesser extent and in decreasing order of free energy. All nucleotides inhibited colony formation in concentrations above 1 micron. A velocity sedimentation cell separation technique was used to obtain cell fractions rich in CFC but poor in CSF-producing cells. Such fractions did not respond to cAMP stimulation. These studies suggest that exogenous cAMP stimulates human bone marrow to form colonies in vitro by increasing the release and/or production of endogenous CSF."}
{"id": "PMID:201917", "title": "Vestibular and somatosensory interaction in the cat vestibular nuclei.", "content": "The vestibular nuclei of cats were explored extracellulary with micropipettes to locate units with a resting discharge rate which responded to rotation in the horizontal plane. These units were examined for somatosensory input from neck and limbs. Fewer than half responded to somatosensory stimulation. The neck region was the body area most effective in influencing unitary activity. The response pattern most often noted was an increase and decrease in discharge frequency when the body was moved towards and away from the recording electrode respectively. Change in discharge rate was observed to be primarily dependant upon neck velocity and not upon absolute neck position. Half of the somatosensory units received input from either the forelimbs or the hindlimbs, while the remaining half responded to both.", "contents": "Vestibular and somatosensory interaction in the cat vestibular nuclei. The vestibular nuclei of cats were explored extracellulary with micropipettes to locate units with a resting discharge rate which responded to rotation in the horizontal plane. These units were examined for somatosensory input from neck and limbs. Fewer than half responded to somatosensory stimulation. The neck region was the body area most effective in influencing unitary activity. The response pattern most often noted was an increase and decrease in discharge frequency when the body was moved towards and away from the recording electrode respectively. Change in discharge rate was observed to be primarily dependant upon neck velocity and not upon absolute neck position. Half of the somatosensory units received input from either the forelimbs or the hindlimbs, while the remaining half responded to both."}
{"id": "PMID:201918", "title": "Voltage dependence of amplitude and time course of inhibitory synaptic current in crayfish muscle.", "content": "The membrane of small crayfish muscle fibers was clamped to potentials between-150 and -20 mV and amplitude and time course of inhibitory postsynaptic currents (IPSCs) were studied. The IPSCs were recorded extracellularly by means of a focal microelectrode and also as total clamp current. The IPSCs lasted about 40 ms and were slowed by depolarization. The rate constant alpha of decay of the IPSC depended on membrane potential E according to the relation alpha= 44 s-1 -e-8.7 V E at 13.5 degrees C. alpha increased with temperature with a Q10 of 1.9 to 2.5. The amplitude iI of the IPSC depended nonlinearly on E and decreased with time after a potential shift. This was partly due to movement of Cl--ions, the difference (E--EI) between clamp potential and reversal potential for the IPSC decreasing to a few mV within several minutes after a shift in E. The inhibitory conductance gI increased up to 30-fold for 100 mV depolarization also changed with time. However, the the inhibitory permeability PI proved to be independent of membrane potential and time. The potential dependence of gI is thus largely due to changes in the internal Cl--concentration.", "contents": "Voltage dependence of amplitude and time course of inhibitory synaptic current in crayfish muscle. The membrane of small crayfish muscle fibers was clamped to potentials between-150 and -20 mV and amplitude and time course of inhibitory postsynaptic currents (IPSCs) were studied. The IPSCs were recorded extracellularly by means of a focal microelectrode and also as total clamp current. The IPSCs lasted about 40 ms and were slowed by depolarization. The rate constant alpha of decay of the IPSC depended on membrane potential E according to the relation alpha= 44 s-1 -e-8.7 V E at 13.5 degrees C. alpha increased with temperature with a Q10 of 1.9 to 2.5. The amplitude iI of the IPSC depended nonlinearly on E and decreased with time after a potential shift. This was partly due to movement of Cl--ions, the difference (E--EI) between clamp potential and reversal potential for the IPSC decreasing to a few mV within several minutes after a shift in E. The inhibitory conductance gI increased up to 30-fold for 100 mV depolarization also changed with time. However, the the inhibitory permeability PI proved to be independent of membrane potential and time. The potential dependence of gI is thus largely due to changes in the internal Cl--concentration."}
{"id": "PMID:201920", "title": "Adenosine as inhibitor of myocardial effects of catecholamines.", "content": "Infusion of adenosine into the coronary arteries of isolated guinea pig hearts produced a dose-dependent inhibition of dP/dtmax caused by bolus injections of isoproterenol (4 X 10(-11) moles). Threshold concentration of adenosine was 10(-7) M and maximal inhibition (90%) occurred at 10(-5) M. Coronary dilation induced by papaverine did not influence the contractile response to catecholamines. In addition to its influence on cardiac performance, adenosine (10(-5) M) effectively inhibited the isoproterenol (10(-7)M) induced initial rise in myocardial levels of cyclic 3'5'-AMP, glucose-1-phosphate and glucose-6-phosphate. Adenosine also antagonized the effect of isoproterenol on adenylate cyclase activity in a crude membrane preparation from guinea pig ventricles; it was without effect on the activity of the membrane phosphodiesterase. Theophylline inhibited the actions of adenosine both on adenylate cyclase activity and on contractile force development. Upon infusion of isoproterenol (3 X 10(-7)M) into the coronary arteries of the isolated heart (perfusion at constant pressure), the adenosine concentration in the effluent perfusate increased within 45 s from 10(-8) M to about 10(-6) M. It thus appears conceivable that in ventricular myocardium endogenously formed adenosine may serve 2 functions: dilation of the coronary arteries and limitation of the inotropic and metabolic effects of catecholamines.", "contents": "Adenosine as inhibitor of myocardial effects of catecholamines. Infusion of adenosine into the coronary arteries of isolated guinea pig hearts produced a dose-dependent inhibition of dP/dtmax caused by bolus injections of isoproterenol (4 X 10(-11) moles). Threshold concentration of adenosine was 10(-7) M and maximal inhibition (90%) occurred at 10(-5) M. Coronary dilation induced by papaverine did not influence the contractile response to catecholamines. In addition to its influence on cardiac performance, adenosine (10(-5) M) effectively inhibited the isoproterenol (10(-7)M) induced initial rise in myocardial levels of cyclic 3'5'-AMP, glucose-1-phosphate and glucose-6-phosphate. Adenosine also antagonized the effect of isoproterenol on adenylate cyclase activity in a crude membrane preparation from guinea pig ventricles; it was without effect on the activity of the membrane phosphodiesterase. Theophylline inhibited the actions of adenosine both on adenylate cyclase activity and on contractile force development. Upon infusion of isoproterenol (3 X 10(-7)M) into the coronary arteries of the isolated heart (perfusion at constant pressure), the adenosine concentration in the effluent perfusate increased within 45 s from 10(-8) M to about 10(-6) M. It thus appears conceivable that in ventricular myocardium endogenously formed adenosine may serve 2 functions: dilation of the coronary arteries and limitation of the inotropic and metabolic effects of catecholamines."}
{"id": "PMID:201921", "title": "[Detection of HBs Ag in bone's metastatic malignant hepatoma (author's transl)].", "content": "A case of metastatic malignant hepatoma in bone, developed in a Vietnamen woman, is reported. Indirect immunofluorescence and orcein staining detect HBs Ag in cytoplasm of many tumor cells. This finding raises pathogenic problems, in particular that of the responsability of heaptitis B virus in the aetiology of certain hepatic tumours.", "contents": "[Detection of HBs Ag in bone's metastatic malignant hepatoma (author's transl)]. A case of metastatic malignant hepatoma in bone, developed in a Vietnamen woman, is reported. Indirect immunofluorescence and orcein staining detect HBs Ag in cytoplasm of many tumor cells. This finding raises pathogenic problems, in particular that of the responsability of heaptitis B virus in the aetiology of certain hepatic tumours."}
{"id": "PMID:201922", "title": "[Inappropriate secretion of ADH during acute respiratory infections due to adenovirus in children (author's transl)].", "content": "Four children aged between 7 and 19 months with severe bronchopneumonia due to adenovirus type 7, proved by virology and/or serology developed severe hyponatraemia. One of them is reported in detail: it was possible to estimate plasma ADH levels and thereby prove the existence of reversible hypersecretion of the hormone. Whilst the syndrome of hyponatraemia with inappropriate secretion of ADH has not yet been reported in association with severe pneumonia in the child, it is known in adults. The limits of the syndrome and its physiopathology are discussed. It may be due either to vagal stimulation as a result of a fall in left aressure, or to central involvement. Therapeutic implications of the problem are emphasized.", "contents": "[Inappropriate secretion of ADH during acute respiratory infections due to adenovirus in children (author's transl)]. Four children aged between 7 and 19 months with severe bronchopneumonia due to adenovirus type 7, proved by virology and/or serology developed severe hyponatraemia. One of them is reported in detail: it was possible to estimate plasma ADH levels and thereby prove the existence of reversible hypersecretion of the hormone. Whilst the syndrome of hyponatraemia with inappropriate secretion of ADH has not yet been reported in association with severe pneumonia in the child, it is known in adults. The limits of the syndrome and its physiopathology are discussed. It may be due either to vagal stimulation as a result of a fall in left aressure, or to central involvement. Therapeutic implications of the problem are emphasized."}
{"id": "PMID:201923", "title": "Capping structures of simian virus 40 19S and 16S mRNAs.", "content": "In vivo [methyl 3H]-labeled SV40 19S and 16S mRNA species were purified and their internal methylation as well as their capping structures analyzed. SV40 viral mRNA sedimenting in the 19S region contains approximately equal proportions of m7GpppAm and m7Gppm6Am, while the 16S mRNA contains mainly m7Gpppm6Am. N6 methyl adenosine is located internally within the RNA chains of both the 19S and 16S species.", "contents": "Capping structures of simian virus 40 19S and 16S mRNAs. In vivo [methyl 3H]-labeled SV40 19S and 16S mRNA species were purified and their internal methylation as well as their capping structures analyzed. SV40 viral mRNA sedimenting in the 19S region contains approximately equal proportions of m7GpppAm and m7Gppm6Am, while the 16S mRNA contains mainly m7Gpppm6Am. N6 methyl adenosine is located internally within the RNA chains of both the 19S and 16S species."}
{"id": "PMID:201924", "title": "Modification of human DNA-dependent RNA polymerase activity by cyclic GMP.", "content": "The effect of low concentrations of cyclic GMP (guanosine 3':5'-cyclic monophosphate) on the in vitro enzymatic activities of DNA-dependent RNA polymerases isolated from human peripheral blood lymphocytes has been investigated. In agreement with earlier studies which employed isolated nuclei as the enzyme source, an increase in the activity of partially purified RNA polymerase I is observed in the presence of cyclic GMP (10(-8) to 10(-10)M). RNA polymerase II activity is inhibited by the presence of cyclic GMP at concentrations between 10(-4) and 10(-10)M. RNA polymerase III activity is stimulated in a bimodal fashion by the presence of cyclic GMP with maximal activity noted at 10(-8) to 10(-10) M and 10(-5)M. In addition, [3H]cyclic GMP binds specifically to chromatographic fractions which are known to contain RNA polymerases I, II and III. This binding to RNA polymerases II and III is apprarently less tenacious as demonstrated by dissociation studies. The observations provide additional evidence for a role for cyclic GMP in the regulation of RNA synthesis.", "contents": "Modification of human DNA-dependent RNA polymerase activity by cyclic GMP. The effect of low concentrations of cyclic GMP (guanosine 3':5'-cyclic monophosphate) on the in vitro enzymatic activities of DNA-dependent RNA polymerases isolated from human peripheral blood lymphocytes has been investigated. In agreement with earlier studies which employed isolated nuclei as the enzyme source, an increase in the activity of partially purified RNA polymerase I is observed in the presence of cyclic GMP (10(-8) to 10(-10)M). RNA polymerase II activity is inhibited by the presence of cyclic GMP at concentrations between 10(-4) and 10(-10)M. RNA polymerase III activity is stimulated in a bimodal fashion by the presence of cyclic GMP with maximal activity noted at 10(-8) to 10(-10) M and 10(-5)M. In addition, [3H]cyclic GMP binds specifically to chromatographic fractions which are known to contain RNA polymerases I, II and III. This binding to RNA polymerases II and III is apprarently less tenacious as demonstrated by dissociation studies. The observations provide additional evidence for a role for cyclic GMP in the regulation of RNA synthesis."}
{"id": "PMID:201925", "title": "High-quality, high-throughput, early whole-body bone scanning.", "content": "99mTc-IDP allows for high-quality, high-throughput and early whole-body bone scanning. Whole-body bone scans obtained at 30 min after intravenous administration of the tracer were compared with the standard and delayed 180 min p.i images. A subtraction technique allowed for the anlysis of the 30 min scans and it was found that in both types of investigation the same clinical information was present. This procedure will therefore increase considerably the throughput of whole-body bone scans in a busy department of nuclear medicine. It is however inadequate for detailed analysis of the skeleton (evaluation of benign bone disease).", "contents": "High-quality, high-throughput, early whole-body bone scanning. 99mTc-IDP allows for high-quality, high-throughput and early whole-body bone scanning. Whole-body bone scans obtained at 30 min after intravenous administration of the tracer were compared with the standard and delayed 180 min p.i images. A subtraction technique allowed for the anlysis of the 30 min scans and it was found that in both types of investigation the same clinical information was present. This procedure will therefore increase considerably the throughput of whole-body bone scans in a busy department of nuclear medicine. It is however inadequate for detailed analysis of the skeleton (evaluation of benign bone disease)."}
{"id": "PMID:201928", "title": "A clinical situation of unusual cardiac pain.", "content": "In conclusion, I believe that nurses have a unique opportunity to help patients cope with pain. Much research is already available to guide us in clinical application. Now we must generate more specific nursing research to provide the scientific rationale needed for our nursing actions. I am convinced that there are reasonable explanations for nursing actions that many of us have found so successful but so difficult to explain or teach to others. As nursing research helps us to explain these phenomena, our teaching and practice of nursing will surely improve.", "contents": "A clinical situation of unusual cardiac pain. In conclusion, I believe that nurses have a unique opportunity to help patients cope with pain. Much research is already available to guide us in clinical application. Now we must generate more specific nursing research to provide the scientific rationale needed for our nursing actions. I am convinced that there are reasonable explanations for nursing actions that many of us have found so successful but so difficult to explain or teach to others. As nursing research helps us to explain these phenomena, our teaching and practice of nursing will surely improve."}
{"id": "PMID:201930", "title": "Cytomegalovirus infection in the neonate and its prevention.", "content": "About 0.5% of infants are infected in utero with cytomegalovirus (CMV). As many as 20% become mentally retarded and a further substantial proportion suffer lesser degrees of brain damage. The need for a vaccine is greater than in the case of rubella. A live, tissue culture-adapted strain of CMV has been shown to produce neutralizing antibody in volunteers without significant side effects or detectable virus excretion. The problems of developing such a vaccine for use in man, namely, attenuation, antigenic differences among virus strains, reactivation of latent infection and oncogenicity, are briefly discussed.", "contents": "Cytomegalovirus infection in the neonate and its prevention. About 0.5% of infants are infected in utero with cytomegalovirus (CMV). As many as 20% become mentally retarded and a further substantial proportion suffer lesser degrees of brain damage. The need for a vaccine is greater than in the case of rubella. A live, tissue culture-adapted strain of CMV has been shown to produce neutralizing antibody in volunteers without significant side effects or detectable virus excretion. The problems of developing such a vaccine for use in man, namely, attenuation, antigenic differences among virus strains, reactivation of latent infection and oncogenicity, are briefly discussed."}
{"id": "PMID:201931", "title": "Carcinoma of the lung presenting with a myeloproliferative disorder. A report of two patients.", "content": "A myeloproliferative disorder, similar to agonogenic myeloid metaplasia, has been described in patients with cancer. Two patients with carcinoma of the lung are described who presented with such a disorder but in whom there was no evidence of bone marrow fibrosis and in one of whom there was no evidence of bone marrow infiltration by tumor. The possible mechanism of this association is discussed.", "contents": "Carcinoma of the lung presenting with a myeloproliferative disorder. A report of two patients. A myeloproliferative disorder, similar to agonogenic myeloid metaplasia, has been described in patients with cancer. Two patients with carcinoma of the lung are described who presented with such a disorder but in whom there was no evidence of bone marrow fibrosis and in one of whom there was no evidence of bone marrow infiltration by tumor. The possible mechanism of this association is discussed."}
{"id": "PMID:201937", "title": "MSH/ACTH4-10 influences on the CAR in human subjects: a negative finding.", "content": "Twenty normal, male, paid volunteers were randomly assigned to MSH/ACTH4-10 or diluent control groups. Following a subcutaneous injection of either 30 mg MSH/ACTH4-10 or diluent, all subjects were placed in an active conditioned avoidance response situation where they learned to avoid a painful electric shock by pressing a key during a safe interval between a warning signal (light) and shock onset. MSH/ACTH4-10 did not influence any parameter of the acquisition or extinction process.  The between subjects' variability of autonomic variables was significantly less for the MSH/ACTH4-10 group. Results indicate that inhibition of extinction of conditioned avoidance responding does not generalize across species from rat to man.", "contents": "MSH/ACTH4-10 influences on the CAR in human subjects: a negative finding. Twenty normal, male, paid volunteers were randomly assigned to MSH/ACTH4-10 or diluent control groups. Following a subcutaneous injection of either 30 mg MSH/ACTH4-10 or diluent, all subjects were placed in an active conditioned avoidance response situation where they learned to avoid a painful electric shock by pressing a key during a safe interval between a warning signal (light) and shock onset. MSH/ACTH4-10 did not influence any parameter of the acquisition or extinction process.  The between subjects' variability of autonomic variables was significantly less for the MSH/ACTH4-10 group. Results indicate that inhibition of extinction of conditioned avoidance responding does not generalize across species from rat to man."}
{"id": "PMID:201938", "title": "Acute influences of some ACTH-related peptides of fighting and adrenocortical activity in male laboratory mice.", "content": "A number of corticotrophin preparations when given acutely enhanced fighting behavior, an event which may be consequent upon elevation of circulating corticosterone. A series of short ACTH analogues (ACTH 11-24, ACTH 4-10) had slight influences on circulating plasma corticosterone values and on fighting behavior. However, 20 microgram ACTH 1-10 given 12 hr before testing did increase fighting C.F. controls. As this compound only caused a slight stimulation of plasma corticosterone titers, the possibility exists of an extra-adrenal influence. One cannot, it appears, eliminate glucocorticoid influences using these preparations in the mouse. Acutely, ACTH 1-24 had virtually no influences on Animex-assessed motor activity but did enhance fighting in castrated mice maintained with either androgen or estrogen. It is tentatively concluded that the ACTH influences on aggression in the mouse are partially mediated via glucocorticoid influences on the CNS combined with an extra adrenal influence of part of the ACTH molecule. A possible reason for the differing acute and chronic influences of ACTH on fighting in mice is presented.", "contents": "Acute influences of some ACTH-related peptides of fighting and adrenocortical activity in male laboratory mice. A number of corticotrophin preparations when given acutely enhanced fighting behavior, an event which may be consequent upon elevation of circulating corticosterone. A series of short ACTH analogues (ACTH 11-24, ACTH 4-10) had slight influences on circulating plasma corticosterone values and on fighting behavior. However, 20 microgram ACTH 1-10 given 12 hr before testing did increase fighting C.F. controls. As this compound only caused a slight stimulation of plasma corticosterone titers, the possibility exists of an extra-adrenal influence. One cannot, it appears, eliminate glucocorticoid influences using these preparations in the mouse. Acutely, ACTH 1-24 had virtually no influences on Animex-assessed motor activity but did enhance fighting in castrated mice maintained with either androgen or estrogen. It is tentatively concluded that the ACTH influences on aggression in the mouse are partially mediated via glucocorticoid influences on the CNS combined with an extra adrenal influence of part of the ACTH molecule. A possible reason for the differing acute and chronic influences of ACTH on fighting in mice is presented."}
{"id": "PMID:201940", "title": "Possible role of dopamine-beta-hydroxylase in the regulation of norepinephrine biosynthesis in rat brain.", "content": "In Experiment 1, the dose-response effects of three dopamine-beta-hydroxylase (DBH) inhibitors (diethyldithiocarbamate, FLA-63 and U-14, 624) on the endogenous levels of norepinephrine and dopamine in pons-medulla of rat brain were determined. In Experiment 2, the effect of low doses of diethylithiocarbamate (2.5 to 120 mg/kg) on the level of norepinephrine-3H produced from dopamine-H3 was determined. The data obtained by extrapolation of the curves in both experiments provided an estimation of the in vivo level of DBH activity and suggested that it was not present in excess. Finally, in Experiment 3, the three DBH inhibitors reduced self-stimulation (a behavior dependent upon catecholamines) in a dose-related manner and intraventricular injections of 1-norepinephrine reinstated normal rates of self-stimulation. The results from the three experiments are consistent with the idea that DBH is involved in the regulation of norepinephrine biosynthesis. The relationship of this finding to our earlier report of a deficit of DBH in post-mortem brains of schizophrenics is discussed.", "contents": "Possible role of dopamine-beta-hydroxylase in the regulation of norepinephrine biosynthesis in rat brain. In Experiment 1, the dose-response effects of three dopamine-beta-hydroxylase (DBH) inhibitors (diethyldithiocarbamate, FLA-63 and U-14, 624) on the endogenous levels of norepinephrine and dopamine in pons-medulla of rat brain were determined. In Experiment 2, the effect of low doses of diethylithiocarbamate (2.5 to 120 mg/kg) on the level of norepinephrine-3H produced from dopamine-H3 was determined. The data obtained by extrapolation of the curves in both experiments provided an estimation of the in vivo level of DBH activity and suggested that it was not present in excess. Finally, in Experiment 3, the three DBH inhibitors reduced self-stimulation (a behavior dependent upon catecholamines) in a dose-related manner and intraventricular injections of 1-norepinephrine reinstated normal rates of self-stimulation. The results from the three experiments are consistent with the idea that DBH is involved in the regulation of norepinephrine biosynthesis. The relationship of this finding to our earlier report of a deficit of DBH in post-mortem brains of schizophrenics is discussed."}
{"id": "PMID:201943", "title": "Paradoxical effects of calcium-glucagon interaction on cardiac muscle contractility of isolated guinea pig atria.", "content": "The interrelationships of calcium and glucagon, and calcium and Isuprel were investigated in spontaneous and paced isolated guinea pig atria. Positive force responses with glucagon were in part both frequency and [Ca+2]o-dependent. Negative inotropic responses were observed with high concentrations of glucagon (5.0 microgram/ml) and calcium (10.0 mM). Persistence of a positive inotropic response of the atria to Isuprel (1.0 microgram/ml) and high [Ca+2]o (10 mM) was seen. Catecholamines stimulate c-AMP production in guinea pig atria while glucagon may not. The negative inotropism produced via calcium-glucagon interaction is consistent with the known inhibitory action of high calcium concentration on adenylyl cyclase and stimulation of phosphodiesterase. It is hypothesized that since glucagon does not activate c-AMP in this tissue then the combined action of high calcium and glucagon leads to degeneration of contractility; with Isuprel and high calcium, atrial contractility is maintained via Isuprel's c-AMP activation.", "contents": "Paradoxical effects of calcium-glucagon interaction on cardiac muscle contractility of isolated guinea pig atria. The interrelationships of calcium and glucagon, and calcium and Isuprel were investigated in spontaneous and paced isolated guinea pig atria. Positive force responses with glucagon were in part both frequency and [Ca+2]o-dependent. Negative inotropic responses were observed with high concentrations of glucagon (5.0 microgram/ml) and calcium (10.0 mM). Persistence of a positive inotropic response of the atria to Isuprel (1.0 microgram/ml) and high [Ca+2]o (10 mM) was seen. Catecholamines stimulate c-AMP production in guinea pig atria while glucagon may not. The negative inotropism produced via calcium-glucagon interaction is consistent with the known inhibitory action of high calcium concentration on adenylyl cyclase and stimulation of phosphodiesterase. It is hypothesized that since glucagon does not activate c-AMP in this tissue then the combined action of high calcium and glucagon leads to degeneration of contractility; with Isuprel and high calcium, atrial contractility is maintained via Isuprel's c-AMP activation."}
{"id": "PMID:201944", "title": "Study into the mechanism of acetylsalicylic acid-induced bronchoconstriction.", "content": "In order to elucidate the mechanism of the acetylsalicylic acid-induced bronchoconstrictor responses which have been observed in asthmatic patients, experiments were done in cats, anesthetized by chloralose, vagotomized, and completely relaxed by infusion of suxamethonium. In about half of the experiments, the sensitivity of the bronchi to 5-hydroxytryptamine (5-HT) was considerably enhanced after the administration of 5--6 mg/kg acetylsalicylic acid, a dose which had previously been shown to suppress prostaglandin (PG) biosynthesis in the bronchi of the cat completely. No further increase in sensitivity to 5-HT occurred when higher doses of the drug were given. Immediate bronchoconstrictor reactions to the injection of acetylsalicylic acid were rare, in most instances the rise in sensitivity developed slowly during a period of about 30 min. The results are consistent with the assumption that PGE2 displays an antagonistic effect to the mediators of asthmatic bronchoconstriction or to their liberation and that inhibition of PG synthesis by acetylsalicylic acid or related drugs eliminate this function and may thus give rise to bronchospasm.", "contents": "Study into the mechanism of acetylsalicylic acid-induced bronchoconstriction. In order to elucidate the mechanism of the acetylsalicylic acid-induced bronchoconstrictor responses which have been observed in asthmatic patients, experiments were done in cats, anesthetized by chloralose, vagotomized, and completely relaxed by infusion of suxamethonium. In about half of the experiments, the sensitivity of the bronchi to 5-hydroxytryptamine (5-HT) was considerably enhanced after the administration of 5--6 mg/kg acetylsalicylic acid, a dose which had previously been shown to suppress prostaglandin (PG) biosynthesis in the bronchi of the cat completely. No further increase in sensitivity to 5-HT occurred when higher doses of the drug were given. Immediate bronchoconstrictor reactions to the injection of acetylsalicylic acid were rare, in most instances the rise in sensitivity developed slowly during a period of about 30 min. The results are consistent with the assumption that PGE2 displays an antagonistic effect to the mediators of asthmatic bronchoconstriction or to their liberation and that inhibition of PG synthesis by acetylsalicylic acid or related drugs eliminate this function and may thus give rise to bronchospasm."}
{"id": "PMID:201941", "title": "Effect of magnesium trisilicate and citric acid on the biovailability of tetracycline in man.", "content": "Oral absorption of tetracycline hydrochloride by human subjects was compared with its absorption when coadministered with magnesium trisilicate, citric acid or magnesium trisilicate-citric acid mixture. Evaluation of the absorption rate was done by means of urinary excretion measurements. The concomitant administration of magnesium trisilicate with tetracycline hydrochloride resulted in a dramatic reduction of the excretion rate of the drug. Ingestion of citric acid with tetracycline showed no significant effect on its absorption. Citric acid administration simultaneously with tetracycline hydrocloride-magnesium trisilicate combination failed to improve the absorption of tetracycline in the presence of magnesium trisilicate contrarily to preveious in vitro results. Conclusions were made that in vitro experiments are not always successful in the prediction of in vivo findings.", "contents": "Effect of magnesium trisilicate and citric acid on the biovailability of tetracycline in man. Oral absorption of tetracycline hydrochloride by human subjects was compared with its absorption when coadministered with magnesium trisilicate, citric acid or magnesium trisilicate-citric acid mixture. Evaluation of the absorption rate was done by means of urinary excretion measurements. The concomitant administration of magnesium trisilicate with tetracycline hydrochloride resulted in a dramatic reduction of the excretion rate of the drug. Ingestion of citric acid with tetracycline showed no significant effect on its absorption. Citric acid administration simultaneously with tetracycline hydrocloride-magnesium trisilicate combination failed to improve the absorption of tetracycline in the presence of magnesium trisilicate contrarily to preveious in vitro results. Conclusions were made that in vitro experiments are not always successful in the prediction of in vivo findings."}
{"id": "PMID:201945", "title": "Effect of clozapine on the sleep pattern in the rat.", "content": "The effect of clozapine on the sleep pattern in the rat was studied after a single injection (2.5--20 mg/kg) and after daily administration for 11 consecutive days (2 X 20 mg/kg/day). After a single injection clozapine significantly suppressed REM sleep in a dose-related way, leaving slow wave sleep (SWS) unchanged. Follwing chronic administration, however, clozapine exerted its most prominent effect on SWS, the enhancement of which persisted for at least 3 days after discontinuation of treatment. REM sleep decreased with the development of tolerance and in the absence of rebound phenomena. The results are discussed in the light of disturbances in brain monoamines and the tolerance these amines developed to repeated administration of clozapine.", "contents": "Effect of clozapine on the sleep pattern in the rat. The effect of clozapine on the sleep pattern in the rat was studied after a single injection (2.5--20 mg/kg) and after daily administration for 11 consecutive days (2 X 20 mg/kg/day). After a single injection clozapine significantly suppressed REM sleep in a dose-related way, leaving slow wave sleep (SWS) unchanged. Follwing chronic administration, however, clozapine exerted its most prominent effect on SWS, the enhancement of which persisted for at least 3 days after discontinuation of treatment. REM sleep decreased with the development of tolerance and in the absence of rebound phenomena. The results are discussed in the light of disturbances in brain monoamines and the tolerance these amines developed to repeated administration of clozapine."}
{"id": "PMID:201946", "title": "Effect of carboxypeptidase N, aprotinin and anti-inflammatory drugs of pyrazolidine type on experimental inflammations in rats.", "content": "Inflammation was induced by application of kaolin into the hind paws of rats and its development under the influence of carboxypeptidase N and aprotinin (Antilysin) was followed and compared with the effect of the phenylbutazone type of drugs. Partly purified rat serum carboxypeptidase N, applied subaponeurally (20 mg/kg) together with a nociceptive agent (kaolin), inhibited the inflammation very effectively. Aprotinin, applied as above (10,000 U/kg), enhanced the inflammatory reaction; if applied intraperitoneally 1 h before kaolin, it displayed anti-inflammatory effects similar to that of phenylbutazone (100 mg/kg). Carboxypeptidase N, administered intraperitoneally before kaolin, had a similar anti-inflammatory effect. The effect of phenylbutazone, ketazon and trimetazon on the bradykinin-induced rat uterus contraction was followed. All these substances inhibit the response of isolated rat uterus to bradykinin. From the results it can be assumed that phenylbutazone, ketazon and trimetazon exercise their effect by blocking centres of the rat uterus which are important for the constrictor effect of bradykinin.", "contents": "Effect of carboxypeptidase N, aprotinin and anti-inflammatory drugs of pyrazolidine type on experimental inflammations in rats. Inflammation was induced by application of kaolin into the hind paws of rats and its development under the influence of carboxypeptidase N and aprotinin (Antilysin) was followed and compared with the effect of the phenylbutazone type of drugs. Partly purified rat serum carboxypeptidase N, applied subaponeurally (20 mg/kg) together with a nociceptive agent (kaolin), inhibited the inflammation very effectively. Aprotinin, applied as above (10,000 U/kg), enhanced the inflammatory reaction; if applied intraperitoneally 1 h before kaolin, it displayed anti-inflammatory effects similar to that of phenylbutazone (100 mg/kg). Carboxypeptidase N, administered intraperitoneally before kaolin, had a similar anti-inflammatory effect. The effect of phenylbutazone, ketazon and trimetazon on the bradykinin-induced rat uterus contraction was followed. All these substances inhibit the response of isolated rat uterus to bradykinin. From the results it can be assumed that phenylbutazone, ketazon and trimetazon exercise their effect by blocking centres of the rat uterus which are important for the constrictor effect of bradykinin."}
{"id": "PMID:201947", "title": "Effect of histamine on cyclic AMP levels in control and antigen-sensitized guinea pig lungs.", "content": "The effect of histamine on cyclic AMP was investigated in control and antigen-sensitized guinea pig lungs. Although histamine elevated the cyclic AMP levels in a dose-dependent manner in both groups, the response was consistently smaller in the sensitized lungs. In vivo pretreatment of control guinea pigs with histamine decreased the subsequent effect of exogenous histamine on cyclic AMP. Phosphodiesterase activity was not different in the two groups and it was not affected by histamine. These results indicate that the process of antigen sensitization results in an altered cyclic AMP response to histamine.", "contents": "Effect of histamine on cyclic AMP levels in control and antigen-sensitized guinea pig lungs. The effect of histamine on cyclic AMP was investigated in control and antigen-sensitized guinea pig lungs. Although histamine elevated the cyclic AMP levels in a dose-dependent manner in both groups, the response was consistently smaller in the sensitized lungs. In vivo pretreatment of control guinea pigs with histamine decreased the subsequent effect of exogenous histamine on cyclic AMP. Phosphodiesterase activity was not different in the two groups and it was not affected by histamine. These results indicate that the process of antigen sensitization results in an altered cyclic AMP response to histamine."}
{"id": "PMID:201948", "title": "Influence of structural changes in the imidazolidine ring of clonidine on hypotensive activity.", "content": "2-(2,6-Dichlorophenylimino)piperimidine with HNO3 (St-404), 2-(2,6-dichlorophenyl)-5,6-dihydroimidazo[2,1-b]thiazole fumarate (compound 44-549) and 1,2,3,5-tetrahydroimidazo[2,1-b]quinazoline with HCl (TIQ) were studied with respect to their effects on blood pressure and heart rate in the anaesthetized, normotensive rat following intravenous administration and in the chloralose-anaesthetized cat by means of infusions via the left vertebral artery. St-404 and compound 44-549 possess central hypotensive and bradycardic activities and display modes of action similar to that of clonidine. Central alpha-adrenergic receptors are presumably involved. In the anaesthetized, normotensive rat St-404 is about 3,400 times less active than clonidine, whereas compound 44-549 is 5 times more effective in lowering arterial pressure. The hypotensive effect of TIQ is brought about by a mechanism of action which is different from that of clonidine. The alpha-sympatholytic properties of TIQ suggested previously by others are not confirmed by the experiments presented in this paper.", "contents": "Influence of structural changes in the imidazolidine ring of clonidine on hypotensive activity. 2-(2,6-Dichlorophenylimino)piperimidine with HNO3 (St-404), 2-(2,6-dichlorophenyl)-5,6-dihydroimidazo[2,1-b]thiazole fumarate (compound 44-549) and 1,2,3,5-tetrahydroimidazo[2,1-b]quinazoline with HCl (TIQ) were studied with respect to their effects on blood pressure and heart rate in the anaesthetized, normotensive rat following intravenous administration and in the chloralose-anaesthetized cat by means of infusions via the left vertebral artery. St-404 and compound 44-549 possess central hypotensive and bradycardic activities and display modes of action similar to that of clonidine. Central alpha-adrenergic receptors are presumably involved. In the anaesthetized, normotensive rat St-404 is about 3,400 times less active than clonidine, whereas compound 44-549 is 5 times more effective in lowering arterial pressure. The hypotensive effect of TIQ is brought about by a mechanism of action which is different from that of clonidine. The alpha-sympatholytic properties of TIQ suggested previously by others are not confirmed by the experiments presented in this paper."}
{"id": "PMID:201949", "title": "Does REM sleep deprivation induce a supersensitivity of dopaminergic receptors in the rat brain?", "content": "The possibility that REM sleep deprivation induces increased sensitivity of rats to the effects of apomorphine was investigated. Rats were deprived of REM sleep by placing them on 6.0 cm platforms for 3 days. Stress control groups consisting of rats placed on 14 cm platforms (control rats) and groups of nonmanipulated animals (normal rats) were used for comparison purposes. Several doses of apomorphine were administered to these 3 groups of animals, and aggressive behavior, stereotyped behavior, verticalization and body temperature were recorded. All measures indicated that REM-deprived rats were more responsive to apomorphine than the normal and control animals, with the exception of verticalization effect, in which both REM-deprived and control animals reacted similarly. These results suggest that REM deprivation induced supersensitivity in brain dopamine receptors. Other possible interpretations are also discussed.", "contents": "Does REM sleep deprivation induce a supersensitivity of dopaminergic receptors in the rat brain? The possibility that REM sleep deprivation induces increased sensitivity of rats to the effects of apomorphine was investigated. Rats were deprived of REM sleep by placing them on 6.0 cm platforms for 3 days. Stress control groups consisting of rats placed on 14 cm platforms (control rats) and groups of nonmanipulated animals (normal rats) were used for comparison purposes. Several doses of apomorphine were administered to these 3 groups of animals, and aggressive behavior, stereotyped behavior, verticalization and body temperature were recorded. All measures indicated that REM-deprived rats were more responsive to apomorphine than the normal and control animals, with the exception of verticalization effect, in which both REM-deprived and control animals reacted similarly. These results suggest that REM deprivation induced supersensitivity in brain dopamine receptors. Other possible interpretations are also discussed."}
{"id": "PMID:201955", "title": "Repair of defect of anterior chest wall with a turnover, dermal-fat, deltopectoral flap: case report.", "content": "We present a case in which a full-thickness defect of the anterior chest wall was closed with a turnover, dermal-fat, deltopectoral flap--with split-skin grafts for the cover. This is a worthwhile alternative procedure to be added to the already numerous techniques currently available for the repair of such defects.", "contents": "Repair of defect of anterior chest wall with a turnover, dermal-fat, deltopectoral flap: case report. We present a case in which a full-thickness defect of the anterior chest wall was closed with a turnover, dermal-fat, deltopectoral flap--with split-skin grafts for the cover. This is a worthwhile alternative procedure to be added to the already numerous techniques currently available for the repair of such defects."}
{"id": "PMID:201956", "title": "The adrenocortical secretion in schizophrenics during chlorpromazine treatment.", "content": "33 cases of schizophrenia received normal food and no premedication. After a clinical improvement which showed itself 3--6 weeks after the beginning of the chlorpromazine treatment, the 17-ketosteroids, the 17-ketogenic steroids and also the electrolytes were dertermined in the blood serum, the erythrocytes and the urine. 12 schizophrenics each received 25 mg of ACTH for three days puring the maximum chlorpromazine dosage. The separate results of examination were tabulated. The final results showed a restriction in the steroid synthesis, an increase in the excretion of potassium through the kidneys along with a decrease in the excretion of sodium. There was an appreciable drop in the sodium potassium concentration in the erythrocytes. It can be assumed that there is a connection between the variations in the membrane permeability to electrolytes and pharmacogenic dyskinesia.", "contents": "The adrenocortical secretion in schizophrenics during chlorpromazine treatment. 33 cases of schizophrenia received normal food and no premedication. After a clinical improvement which showed itself 3--6 weeks after the beginning of the chlorpromazine treatment, the 17-ketosteroids, the 17-ketogenic steroids and also the electrolytes were dertermined in the blood serum, the erythrocytes and the urine. 12 schizophrenics each received 25 mg of ACTH for three days puring the maximum chlorpromazine dosage. The separate results of examination were tabulated. The final results showed a restriction in the steroid synthesis, an increase in the excretion of potassium through the kidneys along with a decrease in the excretion of sodium. There was an appreciable drop in the sodium potassium concentration in the erythrocytes. It can be assumed that there is a connection between the variations in the membrane permeability to electrolytes and pharmacogenic dyskinesia."}
{"id": "PMID:201952", "title": "The mechanism by which the energy is released at the level of the flavoenzyme molecule during the transfer of two electrons.", "content": "The model of a mechanism producing the excitation of two electrons by the rotation of an orbital is presented functioning at the level of the flavoenzyme molecule. According to this model, during the transfer of two electrons from an NADH coenzyme to a flavoenzyme molecule, in a reaction cavity of the flavoprotein, two (Fe2+:S) covalent bonds are formed. Subsequently to the electric polarization induced by the formation of some intermolecular connections and by some fixed ions, and (Fe2+:S) orbital turns with an angle, having the nucleus of the sulfur atom as a pivot point, in such a way that an (Fe2+) ions is left out from the covalent bond, and it is replaced by a proton (released from a water molecule). A new (S:H) orbital is formed. Within this (S:H) orbital, the proton moves towards the nucleus of the sulfur atom, from 2.10 A degrees internuclear distance (position in which the proton was included by the orbital rotation) to 1.36 A degrees internuclear distance--corresponding to the length of the (S:H) covalent bond. By the proton movement, the two electrons of the (S:H) orbital arrive on an excitation state level. Then, they fall to their fundamental level and deliver two quanta of electronic excitation, which are transmitted further and help the synthesis of an ATP molecule.", "contents": "The mechanism by which the energy is released at the level of the flavoenzyme molecule during the transfer of two electrons. The model of a mechanism producing the excitation of two electrons by the rotation of an orbital is presented functioning at the level of the flavoenzyme molecule. According to this model, during the transfer of two electrons from an NADH coenzyme to a flavoenzyme molecule, in a reaction cavity of the flavoprotein, two (Fe2+:S) covalent bonds are formed. Subsequently to the electric polarization induced by the formation of some intermolecular connections and by some fixed ions, and (Fe2+:S) orbital turns with an angle, having the nucleus of the sulfur atom as a pivot point, in such a way that an (Fe2+) ions is left out from the covalent bond, and it is replaced by a proton (released from a water molecule). A new (S:H) orbital is formed. Within this (S:H) orbital, the proton moves towards the nucleus of the sulfur atom, from 2.10 A degrees internuclear distance (position in which the proton was included by the orbital rotation) to 1.36 A degrees internuclear distance--corresponding to the length of the (S:H) covalent bond. By the proton movement, the two electrons of the (S:H) orbital arrive on an excitation state level. Then, they fall to their fundamental level and deliver two quanta of electronic excitation, which are transmitted further and help the synthesis of an ATP molecule."}
{"id": "PMID:201957", "title": "Cyclic AMP in cerebrospinal fluid of manic and depressive patients.", "content": "Cyclic 3',5'-adenosine monophosphate (c-AMP) was measured in cerebrospinal fluid (CSF) of manic and depressive patients with and without probenecid administration both before and during treatment with various psychotropic drugs. Oral probenecid (100 mg/kg) produced substantial c-AMP accumulations in CSF suggesting a probenecid-sensitive transport mechanism for c-AMP. Baseline and probenecid-induced accumulations of c-AMP were not significantly different in manic and depressed patients, while baseline levels in depressed patients were higher than those in neurological controls. Imipramine, amitriptyline, lithium, tryptophan, and electroconvulsant therapies did not significantly alter levels or accumulations of c-AMP in CSF of depressed patients.", "contents": "Cyclic AMP in cerebrospinal fluid of manic and depressive patients. Cyclic 3',5'-adenosine monophosphate (c-AMP) was measured in cerebrospinal fluid (CSF) of manic and depressive patients with and without probenecid administration both before and during treatment with various psychotropic drugs. Oral probenecid (100 mg/kg) produced substantial c-AMP accumulations in CSF suggesting a probenecid-sensitive transport mechanism for c-AMP. Baseline and probenecid-induced accumulations of c-AMP were not significantly different in manic and depressed patients, while baseline levels in depressed patients were higher than those in neurological controls. Imipramine, amitriptyline, lithium, tryptophan, and electroconvulsant therapies did not significantly alter levels or accumulations of c-AMP in CSF of depressed patients."}
{"id": "PMID:201953", "title": "Block diagrams for the study of some endocrine processes.", "content": "With the help of bibliographical data and contributions of the authors two block diagrams have been built. These block diagrams are scheming two processes connected with the exposure of the organism to a moderate physical exercise: (a) the control of the release and the effect of ACTH (b) the control of the release and effect of STH. Some practical conclusion can be drawn regarding the interpretation of the endocrine modifications during exercise including those during standard functional tests.", "contents": "Block diagrams for the study of some endocrine processes. With the help of bibliographical data and contributions of the authors two block diagrams have been built. These block diagrams are scheming two processes connected with the exposure of the organism to a moderate physical exercise: (a) the control of the release and the effect of ACTH (b) the control of the release and effect of STH. Some practical conclusion can be drawn regarding the interpretation of the endocrine modifications during exercise including those during standard functional tests."}
{"id": "PMID:201958", "title": "The role of oestrogen replacement in the climacteric syndrome.", "content": "Using a double-blind placebo-controlled cross-over design, the effect of equine conjugated oestrogens tablets (Premarin) was studied in 20 women with the climacteric syndrome followed during 15 months. Sixteen women were equally improved on placebo and oestrogen. Only 2 patients had an improved sense of well-being on oestrogen and not on placebo. The psychological diagnosis was unrelated to the subjective response to oestrogen or placebo. Performance in psychological tests administered before and during treatment periods was not changed by oestrogen or placebo.", "contents": "The role of oestrogen replacement in the climacteric syndrome. Using a double-blind placebo-controlled cross-over design, the effect of equine conjugated oestrogens tablets (Premarin) was studied in 20 women with the climacteric syndrome followed during 15 months. Sixteen women were equally improved on placebo and oestrogen. Only 2 patients had an improved sense of well-being on oestrogen and not on placebo. The psychological diagnosis was unrelated to the subjective response to oestrogen or placebo. Performance in psychological tests administered before and during treatment periods was not changed by oestrogen or placebo."}
{"id": "PMID:201959", "title": "Costs and benefits of behavioural psychotherapy: a pilot study of neurotics treated by nurse-therapists.", "content": "A pilot study is reported of costs and benefits from behavioural psychotherapy by nurse-therapists for selected neurotic problems. Figures are based on the treatment of 42 neurotics (mainly phobics and obsessive-compulsives) who completed treatment with nurse-therapists in a mean of 9 sessions (16 hours). The year before and after treatment was studied. Apart from significant and lasting reduction in patients' distress, economic benefits to them, their families and the community yielded a worthwhile internal rate of return when benefits from the cohort continue for 3 years, a reasonable assumption on available other evidence. Though untreated phobics did not improve elsewhere over 5 years follow-up, a controlled study would seem desirable.", "contents": "Costs and benefits of behavioural psychotherapy: a pilot study of neurotics treated by nurse-therapists. A pilot study is reported of costs and benefits from behavioural psychotherapy by nurse-therapists for selected neurotic problems. Figures are based on the treatment of 42 neurotics (mainly phobics and obsessive-compulsives) who completed treatment with nurse-therapists in a mean of 9 sessions (16 hours). The year before and after treatment was studied. Apart from significant and lasting reduction in patients' distress, economic benefits to them, their families and the community yielded a worthwhile internal rate of return when benefits from the cohort continue for 3 years, a reasonable assumption on available other evidence. Though untreated phobics did not improve elsewhere over 5 years follow-up, a controlled study would seem desirable."}
{"id": "PMID:201954", "title": "Dynamics of the changes in the cerebral amounts of cyclic AMP and some prostaglandins during cobalt-60 gamma-radiation-induced brain edema.", "content": "The total amounts of cyclic AMP (cAMP), prostaglandin E1 (PGE1) and prostaglandin F2alpha (PGF2alpha) in cerebra have been measured in rats, at constant intervals, up to 18 days after whole body exposure to either a unique moderate dose (500 rads) or a unique lethal dose (750 rads) of cobalt-60 gamma-radiation. The experimental findings indicate that this radiation (i) results in an abrupt short-lasting increase in the amount of cerebral cAMP after a 500 rad-irradiation and a progressive long-lasting increase in its amount after a 750 rad-irradiation, and (ii) induces no change in the normally, existing correlation between cerebral PGE1 and cAMP, but affects deeply the normally existing correlation between cerebral PGF2alpha and cAMP. These biochemical alterations generally parallel the evolution of the radiation-induced brain edema.", "contents": "Dynamics of the changes in the cerebral amounts of cyclic AMP and some prostaglandins during cobalt-60 gamma-radiation-induced brain edema. The total amounts of cyclic AMP (cAMP), prostaglandin E1 (PGE1) and prostaglandin F2alpha (PGF2alpha) in cerebra have been measured in rats, at constant intervals, up to 18 days after whole body exposure to either a unique moderate dose (500 rads) or a unique lethal dose (750 rads) of cobalt-60 gamma-radiation. The experimental findings indicate that this radiation (i) results in an abrupt short-lasting increase in the amount of cerebral cAMP after a 500 rad-irradiation and a progressive long-lasting increase in its amount after a 750 rad-irradiation, and (ii) induces no change in the normally, existing correlation between cerebral PGE1 and cAMP, but affects deeply the normally existing correlation between cerebral PGF2alpha and cAMP. These biochemical alterations generally parallel the evolution of the radiation-induced brain edema."}
{"id": "PMID:201962", "title": "Sonographic patterns in trophoblastic diseases.", "content": "A range of sonographic patterns in patients with hydatidiform moles can be appreciated with gray scale ultrasonography, which more readily reveals areas of internal hemorrhagic degeneration and fetal growth within a molar mass. Sonography may be used to evaluate patients suspected of having recurrent or invasive trophoblastic disease; a focus of invasive trophoblastic tumor can be identified as a cluster of high-amplitude echoes within the myometrium, which is frequently associated with echo-free areas of hemorrhage. The enlargement or regression of theca lutein cysts associated with these disease processes can also be monitored.", "contents": "Sonographic patterns in trophoblastic diseases. A range of sonographic patterns in patients with hydatidiform moles can be appreciated with gray scale ultrasonography, which more readily reveals areas of internal hemorrhagic degeneration and fetal growth within a molar mass. Sonography may be used to evaluate patients suspected of having recurrent or invasive trophoblastic disease; a focus of invasive trophoblastic tumor can be identified as a cluster of high-amplitude echoes within the myometrium, which is frequently associated with echo-free areas of hemorrhage. The enlargement or regression of theca lutein cysts associated with these disease processes can also be monitored."}
{"id": "PMID:201969", "title": "Stimulation by cyclic nucleotides of prostaglandin E production in isolated graafian follicles.", "content": "Rat Graafian follicles isolated intact responded to 8-Br-cyclic AMP and 8-Br-cyclic GMP with increased prostaglandin E (PGE) production during a 6 h incubation. By contrast, 8-Br-cyclic IMP, 8-Br-5' AMP and 8-Br-5' GMP were inactive in this respect. The effect of 8-Br-cyclic AMP and 8-Br-cyclic GMP was noted only after a lag period of about 4 h. Choleragen, LH, and the phosphodiesterase inhibitor (3-isobutyl-l-methyl-xanthine; IBMX) also stimulated PGE production. Actinomycin D and cycloheximide given simultaneously with 8-Br-cyclic AMP or LH prevented the stimulatory effect of these agents. Concomitant addition of arachidonic acid did not overcome the effect of these inhibitors. Administration of hCG in vivo or incubation with LH in vitro did not elevate endogenous ovarian free arachidonate, while PGE production was enhanced. Dexamethasone prevented this stimulatory effect of hCG. Collectively, the results suggest that stimulation of ovarian PGE production by cyclic nucleotides and LH is dependent on de novo synthesis of one or more components of the PG synthetase system rather than on substrate availability. Cyclic nucleotides may mediate the stimulatory effect of gonadotropins on PGE production.", "contents": "Stimulation by cyclic nucleotides of prostaglandin E production in isolated graafian follicles. Rat Graafian follicles isolated intact responded to 8-Br-cyclic AMP and 8-Br-cyclic GMP with increased prostaglandin E (PGE) production during a 6 h incubation. By contrast, 8-Br-cyclic IMP, 8-Br-5' AMP and 8-Br-5' GMP were inactive in this respect. The effect of 8-Br-cyclic AMP and 8-Br-cyclic GMP was noted only after a lag period of about 4 h. Choleragen, LH, and the phosphodiesterase inhibitor (3-isobutyl-l-methyl-xanthine; IBMX) also stimulated PGE production. Actinomycin D and cycloheximide given simultaneously with 8-Br-cyclic AMP or LH prevented the stimulatory effect of these agents. Concomitant addition of arachidonic acid did not overcome the effect of these inhibitors. Administration of hCG in vivo or incubation with LH in vitro did not elevate endogenous ovarian free arachidonate, while PGE production was enhanced. Dexamethasone prevented this stimulatory effect of hCG. Collectively, the results suggest that stimulation of ovarian PGE production by cyclic nucleotides and LH is dependent on de novo synthesis of one or more components of the PG synthetase system rather than on substrate availability. Cyclic nucleotides may mediate the stimulatory effect of gonadotropins on PGE production."}
{"id": "PMID:201975", "title": "[Effect of vincamine on sleep-wakefulness equilibrium in the cat (author's transl)].", "content": "Intra-muscular vincamine in the cat (chronic experimental preparation) causes a change in the equilibrium between sleep and wakefulness. This consists of: (1) an increase in the amount of wakefulness, the duration of which depends on the dose injected (5-10 mg/kg) and the mode of injection (more effective when given in two doses than all at once); (2) a decrease in slow wave sleep (SWS) which often has the appearance of phasic slow wave sleep; (3) a transitory suppression of paradoxical sleep (PS). At the time of recovery there is no rebound either of SWS or PS. The mechanism of vinacamine's action is not understood and some interpretations are suggested.", "contents": "[Effect of vincamine on sleep-wakefulness equilibrium in the cat (author's transl)]. Intra-muscular vincamine in the cat (chronic experimental preparation) causes a change in the equilibrium between sleep and wakefulness. This consists of: (1) an increase in the amount of wakefulness, the duration of which depends on the dose injected (5-10 mg/kg) and the mode of injection (more effective when given in two doses than all at once); (2) a decrease in slow wave sleep (SWS) which often has the appearance of phasic slow wave sleep; (3) a transitory suppression of paradoxical sleep (PS). At the time of recovery there is no rebound either of SWS or PS. The mechanism of vinacamine's action is not understood and some interpretations are suggested."}
{"id": "PMID:201976", "title": "[The E.E.G. of herpes encephalitis in children: 3 cases including one neonate (author's transl)].", "content": "The authors report 3 cases of herpes encephalitis in children aged respectively 15 days, 12 months and 18 months. In all 3 cases E.E.G. activity of a periodic nature was noted, which was continuous or intermittent, lateralised or focal in the temporal region, appearing from the 4th to 7th day. The periodicity (of the E.E.G. complex) was short and their stereotyped appearance particularly unusual in babies. In all 3 children convulsive seizures occurred before the discovery of the periodic activity. The latter was found to change in morphology and timing during the seizures. The disease process led to death of the neonate, and recovery with serious sequellae in the other two children. Possible relationships between the transitory nature of the periodic acitivity, the age and the eventual course of the disease, were discussed.", "contents": "[The E.E.G. of herpes encephalitis in children: 3 cases including one neonate (author's transl)]. The authors report 3 cases of herpes encephalitis in children aged respectively 15 days, 12 months and 18 months. In all 3 cases E.E.G. activity of a periodic nature was noted, which was continuous or intermittent, lateralised or focal in the temporal region, appearing from the 4th to 7th day. The periodicity (of the E.E.G. complex) was short and their stereotyped appearance particularly unusual in babies. In all 3 children convulsive seizures occurred before the discovery of the periodic activity. The latter was found to change in morphology and timing during the seizures. The disease process led to death of the neonate, and recovery with serious sequellae in the other two children. Possible relationships between the transitory nature of the periodic acitivity, the age and the eventual course of the disease, were discussed."}
{"id": "PMID:201977", "title": "[Pseudo-myasthenic syndromes. Clinical and electromyographic review of 4 cases, one with an unusual reaction to lidocaine (author's transl)].", "content": "The authors report 4 cases of pseudo-myasthenic syndrome followed with EMG for a period varying from a few months to 4 years. They go over the electrophysiological points which led to the diagnosis: small amplitude of the muscle potential evoked by simple shock and, in particular, the phenomenon of potentiation which may reach 2000 p. 100 during repetitive stimulation at high frequencies. Study of the behaviour of the muscle potential during ischaemia, which was carried out twice, showed an absence of fatigue of the potential which may be considered a sign of disturbance at the muscle level of the motor-end plate. On the other hand, EMG signs of peripheral neuropathy, which were found 3 times, rather suggests a motor neuropathy responsible for the presynaptic block. In 3 patients guanidine had a beneficial effect and no signs of paraneoplastic aetiology had occurred yet. The fourth case, with a bronchial neoplasm discovered at autopsy, was clearly improved by injectable lidocaine, for which no explanation can be supplied.", "contents": "[Pseudo-myasthenic syndromes. Clinical and electromyographic review of 4 cases, one with an unusual reaction to lidocaine (author's transl)]. The authors report 4 cases of pseudo-myasthenic syndrome followed with EMG for a period varying from a few months to 4 years. They go over the electrophysiological points which led to the diagnosis: small amplitude of the muscle potential evoked by simple shock and, in particular, the phenomenon of potentiation which may reach 2000 p. 100 during repetitive stimulation at high frequencies. Study of the behaviour of the muscle potential during ischaemia, which was carried out twice, showed an absence of fatigue of the potential which may be considered a sign of disturbance at the muscle level of the motor-end plate. On the other hand, EMG signs of peripheral neuropathy, which were found 3 times, rather suggests a motor neuropathy responsible for the presynaptic block. In 3 patients guanidine had a beneficial effect and no signs of paraneoplastic aetiology had occurred yet. The fourth case, with a bronchial neoplasm discovered at autopsy, was clearly improved by injectable lidocaine, for which no explanation can be supplied."}
{"id": "PMID:201978", "title": "[Excessive 7-14-sec positive spikes during REM sleep in monozygotic non-epileptic twins with speech retardation (author's transl)].", "content": "6-14/sec positive spikes (PS) (in our cases 7-14) were observed during 6 all-night sleep, recordings in one pair of monozygotic twins (aged 7 years), who had severe speech retardation, no epilepsy and were otherwise normal (CAT were normal). The EEG during wakefulness and sleep showed multifocal independent spikes over the left mid-temporal and right parieto-occipital area. The 7-14 PS, which were similar in both twins, occurred slightly during light sleep, were absent during slow sleep and were most prominent during REM sleep (mean=6.3 sec of PS bursts/min of REM). During REM sleep, the 7-14 PS bursts were negatively related to bursts of eye movements; PS were 7 times more frequent in the intervals between than during bursts of eye movements. In addition, long bursts of PS (up to 6 sec) might interupt the bursts of eye movements suggesting a functional antagonism between mechanisms (still unclear) responsible for PS and for REM. The predominance of PS during REM sleep and the inverse relationship with eye movements are not peculiar to our case, since similar findings have been reported in other cases (TSUZUKI 1967; OKUMA et al. 1968). During the sleep stages when Ps occurred spontaneously, PS could also be evoked by a click or a tone, with a latency of 1, 5-2 sec.", "contents": "[Excessive 7-14-sec positive spikes during REM sleep in monozygotic non-epileptic twins with speech retardation (author's transl)]. 6-14/sec positive spikes (PS) (in our cases 7-14) were observed during 6 all-night sleep, recordings in one pair of monozygotic twins (aged 7 years), who had severe speech retardation, no epilepsy and were otherwise normal (CAT were normal). The EEG during wakefulness and sleep showed multifocal independent spikes over the left mid-temporal and right parieto-occipital area. The 7-14 PS, which were similar in both twins, occurred slightly during light sleep, were absent during slow sleep and were most prominent during REM sleep (mean=6.3 sec of PS bursts/min of REM). During REM sleep, the 7-14 PS bursts were negatively related to bursts of eye movements; PS were 7 times more frequent in the intervals between than during bursts of eye movements. In addition, long bursts of PS (up to 6 sec) might interupt the bursts of eye movements suggesting a functional antagonism between mechanisms (still unclear) responsible for PS and for REM. The predominance of PS during REM sleep and the inverse relationship with eye movements are not peculiar to our case, since similar findings have been reported in other cases (TSUZUKI 1967; OKUMA et al. 1968). During the sleep stages when Ps occurred spontaneously, PS could also be evoked by a click or a tone, with a latency of 1, 5-2 sec."}
{"id": "PMID:201979", "title": "[Preliminary study of the comparative action of 1 methyl-2 (2 naphtyl) aziridine on kindling effect and on paradoxical sleep (author's transl)].", "content": "Methyl-2 (2 Naphtyl) Aziridine (MNA) is a new agent which has been demonstrated to have effects on paradoxical sleep (PS) and on the levels of cerebral noradrenaline (Yamamoto, 1975). It has been tried on a experimental model of epilepsy, the kindling effect, produced in the cat by repetitive stimulation of the amygdala. The results obtained in the cat confirmed blockage of paradoxical sleep (PS) and revealed a marked reduction in the number of stimuli required to produce the effect. The shortening of the time before the first generalised seizure did not seem attributable to privation of paradoxical sleep. The role of cerebral catecholamine reduction, however, is discussed.", "contents": "[Preliminary study of the comparative action of 1 methyl-2 (2 naphtyl) aziridine on kindling effect and on paradoxical sleep (author's transl)]. Methyl-2 (2 Naphtyl) Aziridine (MNA) is a new agent which has been demonstrated to have effects on paradoxical sleep (PS) and on the levels of cerebral noradrenaline (Yamamoto, 1975). It has been tried on a experimental model of epilepsy, the kindling effect, produced in the cat by repetitive stimulation of the amygdala. The results obtained in the cat confirmed blockage of paradoxical sleep (PS) and revealed a marked reduction in the number of stimuli required to produce the effect. The shortening of the time before the first generalised seizure did not seem attributable to privation of paradoxical sleep. The role of cerebral catecholamine reduction, however, is discussed."}
{"id": "PMID:201980", "title": "Electrophysiological properties of rat heart cells in vitro and in tissue culture.", "content": "Some electrical properties of right ventricles of neonatal rats and of aggregates from collagenase-dissociated cells from the same tissue are compared. The duration of the action potential does not change upon changing the stimulation frequency both in ventricles and aggregates; a decrease in temperature increases duration in both preparations to the same extent. The take-off potential and the maximal rate of rise of the action potential decrease in the same way in both preparations, while the time course of these changes is also comparable. It is concluded that the dissociation and aggregation procedure does not interfere with the membrane properties upon which the measured parameters are based; thus, aggregates are well suited for a realistic voltage-clamp analysis.", "contents": "Electrophysiological properties of rat heart cells in vitro and in tissue culture. Some electrical properties of right ventricles of neonatal rats and of aggregates from collagenase-dissociated cells from the same tissue are compared. The duration of the action potential does not change upon changing the stimulation frequency both in ventricles and aggregates; a decrease in temperature increases duration in both preparations to the same extent. The take-off potential and the maximal rate of rise of the action potential decrease in the same way in both preparations, while the time course of these changes is also comparable. It is concluded that the dissociation and aggregation procedure does not interfere with the membrane properties upon which the measured parameters are based; thus, aggregates are well suited for a realistic voltage-clamp analysis."}
{"id": "PMID:201981", "title": "Quench-flow measurements of initial rates of Ca2+ accumulation by isolated cardiac sarcoplasmic reticulum.", "content": "Using a quench-flow technique, the initial velocity of Ca2+ accumulation by isolated cardiac sarcoplasmic reticulum was estimated at free Ca2+ ion concentrations in the range encountered in the myoplasm during the cardiac contraction cycle. With cardiac microsomes exhibiting a Ca2+ accumulative capacity of 25.6 nmol Ca2+/mg protein, initial rates were found to increase from 3.7 to 33.4 nmol Ca2+/mg protein/sec, when the free Ca2+ ion concentration was raised from 0.2 to 18.0 muM. Preincubation of the cardiac microsomes with a party purified soluble cardiac protein kinase, MgATP, and cAMP led to a significant increase in the initial Ca2+ accumulation rate.", "contents": "Quench-flow measurements of initial rates of Ca2+ accumulation by isolated cardiac sarcoplasmic reticulum. Using a quench-flow technique, the initial velocity of Ca2+ accumulation by isolated cardiac sarcoplasmic reticulum was estimated at free Ca2+ ion concentrations in the range encountered in the myoplasm during the cardiac contraction cycle. With cardiac microsomes exhibiting a Ca2+ accumulative capacity of 25.6 nmol Ca2+/mg protein, initial rates were found to increase from 3.7 to 33.4 nmol Ca2+/mg protein/sec, when the free Ca2+ ion concentration was raised from 0.2 to 18.0 muM. Preincubation of the cardiac microsomes with a party purified soluble cardiac protein kinase, MgATP, and cAMP led to a significant increase in the initial Ca2+ accumulation rate."}
{"id": "PMID:201983", "title": "Characteristics of heart sarcolemmal calcium transport system and effect of protein kinase on sarcolemmal calcium accumulation.", "content": "Properties of the ATP-dependent calcium transport system of heart sarcolemma are presented. Calcium accumulation (with oxalate) in sarcolemma was increased due to cAMP-dependent protein kinase and phosphorylase b kinase. Protein kinase increased the Vmax of the sarcolemmal calcium accumulation without any detectable effect on the affinity for Ca2+. Both kinases failed to stimulate calcium binding. Protein kinase catalyzed phosphorylation of membrane proteins of molecular weights of 100,000, 25,000, and 14,000. Phosphorylase b kinase also catalyzed phosphorylation of these proteins. Protein kinase stimulated ATPase activity of sarcolemma. Sarcolemma contained endogenous protein kinase and protein phosphatase activities.", "contents": "Characteristics of heart sarcolemmal calcium transport system and effect of protein kinase on sarcolemmal calcium accumulation. Properties of the ATP-dependent calcium transport system of heart sarcolemma are presented. Calcium accumulation (with oxalate) in sarcolemma was increased due to cAMP-dependent protein kinase and phosphorylase b kinase. Protein kinase increased the Vmax of the sarcolemmal calcium accumulation without any detectable effect on the affinity for Ca2+. Both kinases failed to stimulate calcium binding. Protein kinase catalyzed phosphorylation of membrane proteins of molecular weights of 100,000, 25,000, and 14,000. Phosphorylase b kinase also catalyzed phosphorylation of these proteins. Protein kinase stimulated ATPase activity of sarcolemma. Sarcolemma contained endogenous protein kinase and protein phosphatase activities."}
{"id": "PMID:201985", "title": "An adenosine 3':5'-monophosphate-dependent protein kinase from human heart.", "content": "Protein kinase that phosphorylated histone and lesser amounts of protamine was demonstrated in human heart. It was activated three times by 10(-6) M cyclic adenosine 3':5'-monophosphate (cAMP) and by 10(-3) M other cyclic nucleotides. Km values for cAMP, ATP, Mg2+, and Co2+ were about 2 X 10(-8) M, 4 X 10(-5) M, 2 X 10(-3)M, and 1.7 X 10(-4) M, respectively. On DEAE cellulose column, the main peak of the enzyme eluted at high NaCl concentration. On Sephadex G-200 gel filtration the majority of the holoenzyme eluted at a peak corresponding to a molecular weight of about 300,000. There was an additional peak corresponding to a molecular weight of about 400,000, with relatively high cAMP binding compared to kinase activity. Right atrium and ventricle showed significantly higher enzyme activities than left atrium and ventricle and interventricular septum. On multivariate analysis of the enzyme activity versus 12 clinical and pathological findings of 122 cases, cardiac hypertrophy and coronary sclerosis were slight but significant negative contributors to the enzyme activity. Multiple correlation coefficient was low, indicating the enzyme activity remained at a relatively stable level, despite different clinical situations. This may be suitable for control of intracellular events through the membrane adenylate cyclase system.", "contents": "An adenosine 3':5'-monophosphate-dependent protein kinase from human heart. Protein kinase that phosphorylated histone and lesser amounts of protamine was demonstrated in human heart. It was activated three times by 10(-6) M cyclic adenosine 3':5'-monophosphate (cAMP) and by 10(-3) M other cyclic nucleotides. Km values for cAMP, ATP, Mg2+, and Co2+ were about 2 X 10(-8) M, 4 X 10(-5) M, 2 X 10(-3)M, and 1.7 X 10(-4) M, respectively. On DEAE cellulose column, the main peak of the enzyme eluted at high NaCl concentration. On Sephadex G-200 gel filtration the majority of the holoenzyme eluted at a peak corresponding to a molecular weight of about 300,000. There was an additional peak corresponding to a molecular weight of about 400,000, with relatively high cAMP binding compared to kinase activity. Right atrium and ventricle showed significantly higher enzyme activities than left atrium and ventricle and interventricular septum. On multivariate analysis of the enzyme activity versus 12 clinical and pathological findings of 122 cases, cardiac hypertrophy and coronary sclerosis were slight but significant negative contributors to the enzyme activity. Multiple correlation coefficient was low, indicating the enzyme activity remained at a relatively stable level, despite different clinical situations. This may be suitable for control of intracellular events through the membrane adenylate cyclase system."}
{"id": "PMID:201984", "title": "Significance of the membrane protein phospholamban in cyclic AMP-mediated regulation of calcium transport by sarcoplasmic reticulum.", "content": "Phospholamban (molecular weight = 22,000), which serves as a regulator of Ca transport ATPase (molecular weight = 100,000) of cardiac sarcoplasmic reticulum (SR), becomes resistant to tryptic digestion upon phosphorylation by cAMP-dependent protein kinase (PK). The protective effect of phosphorylation is accompanied by persistence of the PK-induced stimulation of Ca transport. These findings indicate that structural alteration of phospholamban upon phosphorylation is closely associated with changes in the functional properties of cardiac SR. SR from fast-contracting skeletal muscle of rabbit does not contain a 22,000-dalton substrate for cAMP-dependent PK, nor is Ca transport stimulated by exogenous PK. SR preparation isolated from slow-contracting skeletal muscle of rabbit and dog contains phospholamban, and Ca transport was found to be increased by exogenous cAMP-dependent PK. In view of the distribution of phospholamban among different types of muscle, a hypothesis is presented to explain the relaxation-promoting effects of catecholamines in cardiac and slow-contracting skeletal muscle in which phospholamban is found. This may also account for the absence of a similar effect of catecholamines in fast-contracting skeletal muscle, which does not contain a similar substrate for PK.", "contents": "Significance of the membrane protein phospholamban in cyclic AMP-mediated regulation of calcium transport by sarcoplasmic reticulum. Phospholamban (molecular weight = 22,000), which serves as a regulator of Ca transport ATPase (molecular weight = 100,000) of cardiac sarcoplasmic reticulum (SR), becomes resistant to tryptic digestion upon phosphorylation by cAMP-dependent protein kinase (PK). The protective effect of phosphorylation is accompanied by persistence of the PK-induced stimulation of Ca transport. These findings indicate that structural alteration of phospholamban upon phosphorylation is closely associated with changes in the functional properties of cardiac SR. SR from fast-contracting skeletal muscle of rabbit does not contain a 22,000-dalton substrate for cAMP-dependent PK, nor is Ca transport stimulated by exogenous PK. SR preparation isolated from slow-contracting skeletal muscle of rabbit and dog contains phospholamban, and Ca transport was found to be increased by exogenous cAMP-dependent PK. In view of the distribution of phospholamban among different types of muscle, a hypothesis is presented to explain the relaxation-promoting effects of catecholamines in cardiac and slow-contracting skeletal muscle in which phospholamban is found. This may also account for the absence of a similar effect of catecholamines in fast-contracting skeletal muscle, which does not contain a similar substrate for PK."}
{"id": "PMID:201987", "title": "Phosphoprotein phosphatase-catalyzed dephosphorylation of the 22,000-dalton phosphoprotein of cardiac sarcoplasmic reticulum.", "content": "Similar time courses were obtained for decreases in the rate of calcium transport by cardiac sarcoplasmic reticulum vesicles previously phosphorylated by cAMP-dependent protein kinase and dephosphorylation of the 22,000-dalton phosphoprotein in these membranes. Dephosphorylation of the 22,000-dalton phosphoprotein can be attributed to a phosphoprotein phosphatase in the sarcoplasmic reticular membranes. This membrane-bound phosphoprotein phosphatase may play a role in the reversal of the relaxation-promoting effect of catecholamines on the heart.", "contents": "Phosphoprotein phosphatase-catalyzed dephosphorylation of the 22,000-dalton phosphoprotein of cardiac sarcoplasmic reticulum. Similar time courses were obtained for decreases in the rate of calcium transport by cardiac sarcoplasmic reticulum vesicles previously phosphorylated by cAMP-dependent protein kinase and dephosphorylation of the 22,000-dalton phosphoprotein in these membranes. Dephosphorylation of the 22,000-dalton phosphoprotein can be attributed to a phosphoprotein phosphatase in the sarcoplasmic reticular membranes. This membrane-bound phosphoprotein phosphatase may play a role in the reversal of the relaxation-promoting effect of catecholamines on the heart."}
{"id": "PMID:201986", "title": "Effect of protein kinase modulator on cAMP-dependent protein kinase-catalyzed phosphorylation of phospholamban and stimulation of calcium transport in cardiac sarcoplasmic reticulum.", "content": "The heat-stable protein (protein kinase modulator), partially purified from fresh bovine heart, possessed the ability to inhibit and stimulate adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase and guanosine 3':5'-monophosphate (cGMP)-dependent protein kinase activities, respectively. The inhibitory activity of protein kinase modulator on cAMP-dependent protein kinase was abolished almost completely by trypsin treatment, while the ability to stimulate cGMP-dependent protein kinase activity was resistant to trypsin. Fractionation by a linear potassium phosphate gradient on DEAE-cellulose column did not clearly separate both activities. Phosphorylation of cardiac microsomal component, \"phospholamban\" (molecular weight = 22,000), was inhibited almost completely by the saturating amounts of protein kinase modulator. This inhibition of phospholamban phosphorylation by protein kinase modulator was accompanied by a decreased Ca uptake rate that had been stimulated by cAMP-dependent protein kinase. These findings indicate that protein kinase modulator is functional in controlling the cAMP-dependent protein kinase-catalyzed phosphorylation of phospholamban and the rate of calcium transport, lending further support for the previously proposed mechanism, in which phospholamban is assumed to serve as a regulator of calcium transport in cardiac sarcoplasmic reticulum.", "contents": "Effect of protein kinase modulator on cAMP-dependent protein kinase-catalyzed phosphorylation of phospholamban and stimulation of calcium transport in cardiac sarcoplasmic reticulum. The heat-stable protein (protein kinase modulator), partially purified from fresh bovine heart, possessed the ability to inhibit and stimulate adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase and guanosine 3':5'-monophosphate (cGMP)-dependent protein kinase activities, respectively. The inhibitory activity of protein kinase modulator on cAMP-dependent protein kinase was abolished almost completely by trypsin treatment, while the ability to stimulate cGMP-dependent protein kinase activity was resistant to trypsin. Fractionation by a linear potassium phosphate gradient on DEAE-cellulose column did not clearly separate both activities. Phosphorylation of cardiac microsomal component, \"phospholamban\" (molecular weight = 22,000), was inhibited almost completely by the saturating amounts of protein kinase modulator. This inhibition of phospholamban phosphorylation by protein kinase modulator was accompanied by a decreased Ca uptake rate that had been stimulated by cAMP-dependent protein kinase. These findings indicate that protein kinase modulator is functional in controlling the cAMP-dependent protein kinase-catalyzed phosphorylation of phospholamban and the rate of calcium transport, lending further support for the previously proposed mechanism, in which phospholamban is assumed to serve as a regulator of calcium transport in cardiac sarcoplasmic reticulum."}
{"id": "PMID:201988", "title": "Effect of increased cAMP content on extracellular distribution of calcium and contractility in rabbit heart.", "content": "Norepinephrine, dexamethasone, and papaverine hydrochloride caused a significant increase in myocardial cAMP level and an alteration of intracellular distribution of Ca, such as the reduction of Ca content on mitochondrial and microsomal fractions, with or without positive inotropic effects, in the rabbit. Positive inotropic effects evoked by norepinephrine were significantly increased under the elevated level of cAMP induced by dexamethasone and papaverine. On the other hand, verapamil showed no effects on cAMP concentration and intracellular Ca distribution of the heart. These results indicate that the accumulation of myocardial cAMP may result in the alteration of intracellular distribution of Ca, and it is suggested that there is an increase in the available Ca for contractile and metabolic mechanisms of the heart.", "contents": "Effect of increased cAMP content on extracellular distribution of calcium and contractility in rabbit heart. Norepinephrine, dexamethasone, and papaverine hydrochloride caused a significant increase in myocardial cAMP level and an alteration of intracellular distribution of Ca, such as the reduction of Ca content on mitochondrial and microsomal fractions, with or without positive inotropic effects, in the rabbit. Positive inotropic effects evoked by norepinephrine were significantly increased under the elevated level of cAMP induced by dexamethasone and papaverine. On the other hand, verapamil showed no effects on cAMP concentration and intracellular Ca distribution of the heart. These results indicate that the accumulation of myocardial cAMP may result in the alteration of intracellular distribution of Ca, and it is suggested that there is an increase in the available Ca for contractile and metabolic mechanisms of the heart."}
{"id": "PMID:201989", "title": "Effects of catecholamines on myocardial energy metabolism as studied by an organ redoximeter.", "content": "With the use of an organ redoximeter, the effects of noradrenaline, adrenaline, isoproterenol, and phenylephrine on the oxidation-reduction state of the myocardial pyridine nucleotides were studied in the canine heart-lung preparation supported by a donor. Noradrenaline and adrenaline produced an initial, transient improvement, and phenylephrine a sustained improvement, of the redox state, while isoproterenol produced a depression. Pretreatment of the preparation with adrenergic alpha-blockers resulted in an abolishment of the improvement by noradrenaline, adrenaline, and phenylephrine, while the depression by isoproterenol remained unchanged. Whereas noradrenaline and adrenaline produced a sustained improvement after an adrenergic beta-blocker, propranolol, the effect of isoproterenol was abolished. These findings suggest that sympathomimetic amines can produce an improvement of the myocardial energy metabolism through activation of the adrenergic alpha-receptor. The depression of the myocardial oxidation-reduction state was taken to represent an acceleration of glycolysis.", "contents": "Effects of catecholamines on myocardial energy metabolism as studied by an organ redoximeter. With the use of an organ redoximeter, the effects of noradrenaline, adrenaline, isoproterenol, and phenylephrine on the oxidation-reduction state of the myocardial pyridine nucleotides were studied in the canine heart-lung preparation supported by a donor. Noradrenaline and adrenaline produced an initial, transient improvement, and phenylephrine a sustained improvement, of the redox state, while isoproterenol produced a depression. Pretreatment of the preparation with adrenergic alpha-blockers resulted in an abolishment of the improvement by noradrenaline, adrenaline, and phenylephrine, while the depression by isoproterenol remained unchanged. Whereas noradrenaline and adrenaline produced a sustained improvement after an adrenergic beta-blocker, propranolol, the effect of isoproterenol was abolished. These findings suggest that sympathomimetic amines can produce an improvement of the myocardial energy metabolism through activation of the adrenergic alpha-receptor. The depression of the myocardial oxidation-reduction state was taken to represent an acceleration of glycolysis."}
{"id": "PMID:201990", "title": "Characteristics of energy metabolism in specialized muscle of bovine heart.", "content": "Characterization of the energy metabolism pattern of the specialized heart muscle of bovine heart was studied in comparison with that of the ordinary heart muscle. Mitochondrial oxygen consumption of the specialized heart muscle was significantly lower than that of the ordinary heart muscle with succinate as the substrate. On the other hand, there was no significant difference in oxygen consumption between both heart muscles with glutamate + malate as the substrates. The activity levels of succinate dehydrogenase and lactate dehydrogenase were much lower than those of the ordinary heart muscle. The isozyme pattern of LDH of the specialized heart muscle consisted of one major component of LDH-1 (H4)  and that of the ordinary heart muscle consisted of two major components of LDH-1 (H4) and LDH-2 (H3M). The ratio of NADH to NAD of the specialized heart muscle was remarkably lower than that of the ordinary heart muscle. These results indicate that the specialized heart muscle depends not only upon anaerobic metabolism but also upon aerobic metabolism for its energy supply.", "contents": "Characteristics of energy metabolism in specialized muscle of bovine heart. Characterization of the energy metabolism pattern of the specialized heart muscle of bovine heart was studied in comparison with that of the ordinary heart muscle. Mitochondrial oxygen consumption of the specialized heart muscle was significantly lower than that of the ordinary heart muscle with succinate as the substrate. On the other hand, there was no significant difference in oxygen consumption between both heart muscles with glutamate + malate as the substrates. The activity levels of succinate dehydrogenase and lactate dehydrogenase were much lower than those of the ordinary heart muscle. The isozyme pattern of LDH of the specialized heart muscle consisted of one major component of LDH-1 (H4)  and that of the ordinary heart muscle consisted of two major components of LDH-1 (H4) and LDH-2 (H3M). The ratio of NADH to NAD of the specialized heart muscle was remarkably lower than that of the ordinary heart muscle. These results indicate that the specialized heart muscle depends not only upon anaerobic metabolism but also upon aerobic metabolism for its energy supply."}
{"id": "PMID:201992", "title": "Evidence for opposing influences of cyclic GMP and cyclic AMP on force of contraction in mammalian myocardium.", "content": "The inotropic effects of the 8-Br-derivatives of cyclic GMP and cyclic AMP were investigated in guinea pig or rat auricles and papillary muscles from cats. In guinea pig auricles, 8-Br-cyclic GMP had a concentration-dependent negative inotropic effect, whereas 8-Br-cyclic AMP had a concentration-dependent positive inotropic effect. A negative inotropic effect of 8-Br-cyclic GMP in rat auricles was obtained with 30 times lower doses than in guinea pig auricles; the pacemaker activity of spontaneously beating rat right auricles did not change in response to 8-Br-cyclic GMP. In cat papillary muscles, 8-Br-cyclic GMP (3 X 10(-4) M) also produced a negative inotropic effect. In contrast, 8-Br-cyclic AMP (3 X 10(-4) M) did not affect force of contraction; however, after pretreatment with the strong phosphodiesterase inhibitor papaverine (2 X 10(-5) M) 8-Br-cyclic AMP (3 X 10(-4) M) had a strong positive inotropic effect also in cat papillary muscles. The results suggest opposite influences of cyclic GMP and cyclic AMP on force of contraction in mammalian myocardium.", "contents": "Evidence for opposing influences of cyclic GMP and cyclic AMP on force of contraction in mammalian myocardium. The inotropic effects of the 8-Br-derivatives of cyclic GMP and cyclic AMP were investigated in guinea pig or rat auricles and papillary muscles from cats. In guinea pig auricles, 8-Br-cyclic GMP had a concentration-dependent negative inotropic effect, whereas 8-Br-cyclic AMP had a concentration-dependent positive inotropic effect. A negative inotropic effect of 8-Br-cyclic GMP in rat auricles was obtained with 30 times lower doses than in guinea pig auricles; the pacemaker activity of spontaneously beating rat right auricles did not change in response to 8-Br-cyclic GMP. In cat papillary muscles, 8-Br-cyclic GMP (3 X 10(-4) M) also produced a negative inotropic effect. In contrast, 8-Br-cyclic AMP (3 X 10(-4) M) did not affect force of contraction; however, after pretreatment with the strong phosphodiesterase inhibitor papaverine (2 X 10(-5) M) 8-Br-cyclic AMP (3 X 10(-4) M) had a strong positive inotropic effect also in cat papillary muscles. The results suggest opposite influences of cyclic GMP and cyclic AMP on force of contraction in mammalian myocardium."}
{"id": "PMID:201996", "title": "Studies on myocardial mitochondria in failing dog hearts: studies by electron spin resonance (ESR) spectrometry.", "content": "The formation of free radicals, which was represented by the concentration of free radicals in state 4 respiration, and the respiratory control ratio were studied in the myocardial mitochondria isolated from dog hearts that were failing due to aortic constriction. Both formation and respiratory control ratio were lowered, compared to each control value, in acute and chronic heart failure. A positive correlation was recognized between free radicals in state 4 respiration and respiratory control ratio. From these results it was concluded that there was uncoupling of oxidative phosphorylation in the mitochondria isolated from failing dog hearts. Measurement of free radicals in state 4 respiration, as well as respiratory control ratio, is a useful method for evaluation of the function of oxidative phosphorylation.", "contents": "Studies on myocardial mitochondria in failing dog hearts: studies by electron spin resonance (ESR) spectrometry. The formation of free radicals, which was represented by the concentration of free radicals in state 4 respiration, and the respiratory control ratio were studied in the myocardial mitochondria isolated from dog hearts that were failing due to aortic constriction. Both formation and respiratory control ratio were lowered, compared to each control value, in acute and chronic heart failure. A positive correlation was recognized between free radicals in state 4 respiration and respiratory control ratio. From these results it was concluded that there was uncoupling of oxidative phosphorylation in the mitochondria isolated from failing dog hearts. Measurement of free radicals in state 4 respiration, as well as respiratory control ratio, is a useful method for evaluation of the function of oxidative phosphorylation."}
{"id": "PMID:201995", "title": "Effects of acetylcholine and cyclic nucleotides on the bullfrog atrial muscle.", "content": "Effects of ACh on the slow inward current and tension components of bullfrog atrial muscle were examined with voltage-clamp technique. ACh decreased the phasic component of contractile tension and the slow inward current with a reduction of gCa. Contracture tensions were augmented by ACh and decreased by adrenaline. Intracellularly injected cGMP through microelectrode decreased the overshoot and the plateau level of action potential without affecting the resting membrane potential, indicating a decrease in the slow inward current. cAMP enhanced the overshoot and the plateau. ACh seems to reduce the slow inward current through an elevation of intracellular cGMP concentrations.", "contents": "Effects of acetylcholine and cyclic nucleotides on the bullfrog atrial muscle. Effects of ACh on the slow inward current and tension components of bullfrog atrial muscle were examined with voltage-clamp technique. ACh decreased the phasic component of contractile tension and the slow inward current with a reduction of gCa. Contracture tensions were augmented by ACh and decreased by adrenaline. Intracellularly injected cGMP through microelectrode decreased the overshoot and the plateau level of action potential without affecting the resting membrane potential, indicating a decrease in the slow inward current. cAMP enhanced the overshoot and the plateau. ACh seems to reduce the slow inward current through an elevation of intracellular cGMP concentrations."}
{"id": "PMID:201997", "title": "Arrhythmogenic effects of acute free fatty acid mobilization on ischemic heart.", "content": "The mechanism of action of the acute abnormal rise of plasma free fatty acids (FFA) in the provocation of arrhythmia in ischemic heart was studied by means of electron spin resonance (ESR) spectrometer. A sudden and abnormal rise of plasma FFA caused a significant fall of the respiratory control index (RCI) of the amount of free radical myocardial mitochondria in state 4 respiration. Based on these findings, a sudden and abnormal rise of plasma FFA seems to further facilitate the uncoupling of oxidative phosphorylation in the myocardial mitochondria of the ischemic portion of the heart. These observations indicate that it may play an important role in the provocation of arrhythmia by high plasma FFA on the ischemic heart. Nicomol (2,2,6,6,-tetrakis (nicotinoyloxymethyl) cyclohexanol), an inhibitor for the rapid rise of plasma FFA, was effective in the treatment and prevention of arrhythmia in ischemic heart disease and diabetes mellitus.", "contents": "Arrhythmogenic effects of acute free fatty acid mobilization on ischemic heart. The mechanism of action of the acute abnormal rise of plasma free fatty acids (FFA) in the provocation of arrhythmia in ischemic heart was studied by means of electron spin resonance (ESR) spectrometer. A sudden and abnormal rise of plasma FFA caused a significant fall of the respiratory control index (RCI) of the amount of free radical myocardial mitochondria in state 4 respiration. Based on these findings, a sudden and abnormal rise of plasma FFA seems to further facilitate the uncoupling of oxidative phosphorylation in the myocardial mitochondria of the ischemic portion of the heart. These observations indicate that it may play an important role in the provocation of arrhythmia by high plasma FFA on the ischemic heart. Nicomol (2,2,6,6,-tetrakis (nicotinoyloxymethyl) cyclohexanol), an inhibitor for the rapid rise of plasma FFA, was effective in the treatment and prevention of arrhythmia in ischemic heart disease and diabetes mellitus."}
{"id": "PMID:201998", "title": "Adenylate cyclase, cyclic nucleotide phosphodiesterase, and phosphorylase activity of cardiomyopathic hamster hearts.", "content": "Activities of adenylate cyclase in homogenates were reduced, whereas those of phosphodiesterases were elevated in hearts of myopathic hamsters (BIO 82.62). Affinities for either Mg2+ or ATP of cyclase were unaffected in myopathy. Ca2+ stimulation particulate phosphodiesterases was not observed in myopathy. Although the cardiac phosphorylase content was reduced at the advanced stages of myopathy,-AMP/+AMP ratios remained similar to those found in normal hearts.", "contents": "Adenylate cyclase, cyclic nucleotide phosphodiesterase, and phosphorylase activity of cardiomyopathic hamster hearts. Activities of adenylate cyclase in homogenates were reduced, whereas those of phosphodiesterases were elevated in hearts of myopathic hamsters (BIO 82.62). Affinities for either Mg2+ or ATP of cyclase were unaffected in myopathy. Ca2+ stimulation particulate phosphodiesterases was not observed in myopathy. Although the cardiac phosphorylase content was reduced at the advanced stages of myopathy,-AMP/+AMP ratios remained similar to those found in normal hearts."}
{"id": "PMID:201999", "title": "Differential responses of canine myosin ATPase activity and tissue gases in the pressure-overloaded ventricle dependent upon degree of obstruction: mild versus severe pulmonic and aortic stenosis.", "content": "Mild pulmonic stenosis, induced in dogs by banding the pulmonary artery, elevated right ventricular peak systolic pressure to 60% above the control and elevated right ventricular K+- and Ca2+- activated myosin ATPase activities. In contrast, severe pulmonic stenosis, which elevated right ventricular peak systolic pressure to 300% above the control, did not produce an increase in myosin enzymatic ATPase Vmax values but caused a decrease in myosin activity. Mild aortic stenosis, induced by banding the ascending aorta, forcing a transaortic pressure gradient of 25 mm Hg, caused an elevation in left ventricular muosin ATPase, whereas severe aortic banding, brought about by creating a transaortic pressure gradient of 55 mm Hg, never caused an elevation in left ventricular myosin enzymatic Vmax values, but, like severe pulmonic banding, caused a decrease in K+- and Ca2+- activated myosin activities. Normal left ventricular myosin Vmax values in mumol of PO4/mg-min at 37 degrees C were: K+ = 2.84 +/- 0.22, and Ca2+ = 0.97 +/- 0.14. For right ventricular myosin they were: K+ = 2.15 +/- 0.16, and Ca2+ =0.74 +/- 0.10. Analyses of tissue gases, based on mass spectrometry data, showed that the hypertrophied ventricles had an elevated tissue pCO2 and an elevation in the cGMP/cAMP ratio.", "contents": "Differential responses of canine myosin ATPase activity and tissue gases in the pressure-overloaded ventricle dependent upon degree of obstruction: mild versus severe pulmonic and aortic stenosis. Mild pulmonic stenosis, induced in dogs by banding the pulmonary artery, elevated right ventricular peak systolic pressure to 60% above the control and elevated right ventricular K+- and Ca2+- activated myosin ATPase activities. In contrast, severe pulmonic stenosis, which elevated right ventricular peak systolic pressure to 300% above the control, did not produce an increase in myosin enzymatic ATPase Vmax values but caused a decrease in myosin activity. Mild aortic stenosis, induced by banding the ascending aorta, forcing a transaortic pressure gradient of 25 mm Hg, caused an elevation in left ventricular muosin ATPase, whereas severe aortic banding, brought about by creating a transaortic pressure gradient of 55 mm Hg, never caused an elevation in left ventricular myosin enzymatic Vmax values, but, like severe pulmonic banding, caused a decrease in K+- and Ca2+- activated myosin activities. Normal left ventricular myosin Vmax values in mumol of PO4/mg-min at 37 degrees C were: K+ = 2.84 +/- 0.22, and Ca2+ = 0.97 +/- 0.14. For right ventricular myosin they were: K+ = 2.15 +/- 0.16, and Ca2+ =0.74 +/- 0.10. Analyses of tissue gases, based on mass spectrometry data, showed that the hypertrophied ventricles had an elevated tissue pCO2 and an elevation in the cGMP/cAMP ratio."}
{"id": "PMID:202003", "title": "Effects of adrenaline and methylisobutylxanthine on adenosine 3':5'-monophosphate levels in cultures of beating heart cells of the newborn rat.", "content": "(-)-Adrenaline caused concentration-dependent increases in cAMP levels and the rate of beating in eight-day-old heart cell cultures of newborn rats. Half-maximal increases in both parameters (5- and 0.2 -fold, respectively) occurred at about 10(-6)M. Following the addition of 3 X 10(-7) M adrenaline, the cellular cAMP level rose to a max imum in 30 sec. The rise was abolished by 5 X 10(-8) M (-)-propranolol and was greatly magnified by 10(-4) M 1-methyl-3-isobutylxanthine. In the presence of the latter compound, the average rate of accumulation of cAMP in thecultures during the first 10 seconds of exposure to 3 X 10(-7) M adrenaline was 8.78 pmol/mg of protein-sec, which is 230 times more rapid than the basal accumulation rate. These findings may be taken as evidence in support of the view that cAMP is involved in the positive chronotropic action of adrenaline on cardiac pacemaker cells.", "contents": "Effects of adrenaline and methylisobutylxanthine on adenosine 3':5'-monophosphate levels in cultures of beating heart cells of the newborn rat. (-)-Adrenaline caused concentration-dependent increases in cAMP levels and the rate of beating in eight-day-old heart cell cultures of newborn rats. Half-maximal increases in both parameters (5- and 0.2 -fold, respectively) occurred at about 10(-6)M. Following the addition of 3 X 10(-7) M adrenaline, the cellular cAMP level rose to a max imum in 30 sec. The rise was abolished by 5 X 10(-8) M (-)-propranolol and was greatly magnified by 10(-4) M 1-methyl-3-isobutylxanthine. In the presence of the latter compound, the average rate of accumulation of cAMP in thecultures during the first 10 seconds of exposure to 3 X 10(-7) M adrenaline was 8.78 pmol/mg of protein-sec, which is 230 times more rapid than the basal accumulation rate. These findings may be taken as evidence in support of the view that cAMP is involved in the positive chronotropic action of adrenaline on cardiac pacemaker cells."}
{"id": "PMID:202002", "title": "The effect of the reciprocal relationship of Ca2+ and cAMP on the control of beating in cultured rat heart cells.", "content": "The demonstration of Ca2+ control of the cAMP level in heart cells and the localization of the Ca2+ activator protein of cAMP phosphodiesterase on the sarcoplasmic reticulum (SR) have led us to postulate a model whereby the Ca2+ flux is related to the cAMP flux. The model suggests that the increase in cytosol Ca2+ automatically results in an increase in SR Ca2+ and a subsequent decrease in cAMP to allow for the periodic flux of Ca2+ and cAMP in the contraction cycle.", "contents": "The effect of the reciprocal relationship of Ca2+ and cAMP on the control of beating in cultured rat heart cells. The demonstration of Ca2+ control of the cAMP level in heart cells and the localization of the Ca2+ activator protein of cAMP phosphodiesterase on the sarcoplasmic reticulum (SR) have led us to postulate a model whereby the Ca2+ flux is related to the cAMP flux. The model suggests that the increase in cytosol Ca2+ automatically results in an increase in SR Ca2+ and a subsequent decrease in cAMP to allow for the periodic flux of Ca2+ and cAMP in the contraction cycle."}
{"id": "PMID:202000", "title": "cAMP activity and isoproterenol-induced myocardial injury in rats.", "content": "Isoproterenol-induced myocardial necrosis (ISO-MN) was obviated by the cardioselective beta-blocker, practolol, suggesting that ISO-MN is caused by specific activation of myocardial beta-adrenergic receptors. Because cAMP is the \"second messenger\" in such activation, enhanced activity of cAMP should aggravate ISO-MN. Pretreatment of rats with bretylium in various amounts, elicited no ill effects but enhanced the effects of ISO on the cAMP activity and also intensified the ISO-induced structural changes in the myocardium.", "contents": "cAMP activity and isoproterenol-induced myocardial injury in rats. Isoproterenol-induced myocardial necrosis (ISO-MN) was obviated by the cardioselective beta-blocker, practolol, suggesting that ISO-MN is caused by specific activation of myocardial beta-adrenergic receptors. Because cAMP is the \"second messenger\" in such activation, enhanced activity of cAMP should aggravate ISO-MN. Pretreatment of rats with bretylium in various amounts, elicited no ill effects but enhanced the effects of ISO on the cAMP activity and also intensified the ISO-induced structural changes in the myocardium."}
{"id": "PMID:202010", "title": "Arteriography of the hand.", "content": "Eight cases of vascular lesions of the hand are presented to demonstrate the value of arteriography in these entities. Arteriography provides a valuable tool not only to establish a diagnosis but also for the preoperative planning of repair of injuried vessels in the hand.", "contents": "Arteriography of the hand. Eight cases of vascular lesions of the hand are presented to demonstrate the value of arteriography in these entities. Arteriography provides a valuable tool not only to establish a diagnosis but also for the preoperative planning of repair of injuried vessels in the hand."}
{"id": "PMID:202004", "title": "Cardiomyopathy in vitro.", "content": "Phase contrast microscopy of cultured embryonic heart cells showed the beating frequency decreased more rapidly and the regularity the rhythm of of the beating cells was lost sooner in heart cells from cardiomyopathic hamsters than from the control hamsters. Studies of cultured heart cells by differential interference contrast (with Nomarski's prism) and by electron microscopy revealed a significant impediment in the maturation of the sarcomeric units in the diseased animals compared to controls. The incorporation of [14C] leucine into acid-insoluble fractions was studied, and no significant difference in incorporation between the two groups was found. An analysis of polyacrylamide gel electrophoresis revealed the possible existence of a quantitative difference in one of the composing proteins of the erythrocyte membrane between the two groups. The protein kinase activity of ghosts from the control group was more sensitive to cAMP than that from the diseased animals. In addition, the binding of [3H] cAMP to the ghost was almost identical between the two. The morphological and biochemical observations lead one to the plausible supposition that there are some differences in the interaction of the so-called catalytic and regulatory subunits between the two groups and that there is an impairment of the higher arrangement of myofibrils from their building blocks in the diseased hamster. The significance of the existence of abundant corpuscles resembling neurosecretory granules was not established by this study. They may have an etiological significance or they may be related to a disturbed function in the cultured cells of the cardiomyopathic hamster.", "contents": "Cardiomyopathy in vitro. Phase contrast microscopy of cultured embryonic heart cells showed the beating frequency decreased more rapidly and the regularity the rhythm of of the beating cells was lost sooner in heart cells from cardiomyopathic hamsters than from the control hamsters. Studies of cultured heart cells by differential interference contrast (with Nomarski's prism) and by electron microscopy revealed a significant impediment in the maturation of the sarcomeric units in the diseased animals compared to controls. The incorporation of [14C] leucine into acid-insoluble fractions was studied, and no significant difference in incorporation between the two groups was found. An analysis of polyacrylamide gel electrophoresis revealed the possible existence of a quantitative difference in one of the composing proteins of the erythrocyte membrane between the two groups. The protein kinase activity of ghosts from the control group was more sensitive to cAMP than that from the diseased animals. In addition, the binding of [3H] cAMP to the ghost was almost identical between the two. The morphological and biochemical observations lead one to the plausible supposition that there are some differences in the interaction of the so-called catalytic and regulatory subunits between the two groups and that there is an impairment of the higher arrangement of myofibrils from their building blocks in the diseased hamster. The significance of the existence of abundant corpuscles resembling neurosecretory granules was not established by this study. They may have an etiological significance or they may be related to a disturbed function in the cultured cells of the cardiomyopathic hamster."}
{"id": "PMID:202005", "title": "Electron microscopic cytochemistry of cytochrome oxidase activity in the conduction system of the canine heart.", "content": "Histochemistry and electron microscopic cytochemistry of cytochrome oxidase in the conduction system were studied with the 3,3'-diaminobenzidine (DAB) method in adult canine hearts. This enzyme was distinctly less active in the entire conduction system than in the working myocardium. By electron microscopy, enzymatic activity per cristal membrane was apparently similar in both specialized and working cardiocytes. However, the volume fraction of cell occupied by mitochondria and the density of cristal membranes in mitochondria were smaller in the specialized cells in the sinus node, atrioventricular (AV) node, His bundle, and Purkinje fibers. These observations define the nature of decreased histochemical activity of cytochrome oxidase in cells of the conduction system, which is caused entirely by the decrease in activity per unit of mitochondrial volume and unit of cell volume in the specialized cardiac tissues.", "contents": "Electron microscopic cytochemistry of cytochrome oxidase activity in the conduction system of the canine heart. Histochemistry and electron microscopic cytochemistry of cytochrome oxidase in the conduction system were studied with the 3,3'-diaminobenzidine (DAB) method in adult canine hearts. This enzyme was distinctly less active in the entire conduction system than in the working myocardium. By electron microscopy, enzymatic activity per cristal membrane was apparently similar in both specialized and working cardiocytes. However, the volume fraction of cell occupied by mitochondria and the density of cristal membranes in mitochondria were smaller in the specialized cells in the sinus node, atrioventricular (AV) node, His bundle, and Purkinje fibers. These observations define the nature of decreased histochemical activity of cytochrome oxidase in cells of the conduction system, which is caused entirely by the decrease in activity per unit of mitochondrial volume and unit of cell volume in the specialized cardiac tissues."}
{"id": "PMID:202013", "title": "Characterization of high density lipoproteins in human cholestasis.", "content": "High density lipoproteins (HDL) of plasma from patients with long-standing cholestasis were studied by several methods including crossed immunoelectrophoresis, gel filtration, and zonal ultracentrifugation. The crossed immunoelectrophoretic pattern against anti-HDL was characterized by the presence of several immunoprecipitates, in striking contrast to the pattern formed by normal HDL. One of these precipitates corresponded to a lipoprotein species dominated by apoprotein A-II (apo A-II). Zonal ultracentrifugation of cholestatic plasma showed a decrease of HDL and a disappearance of the normal delineation of HDL2 and HDL3. In addition a new component designated HDL1-C was observed. Consistent results were found at studies of the molecular size distribution of cholestatic HDL by gel filtration on Sephadex G-200. The lipid and apoprotein composition of isolated cholestatic HDL fractions differed considerably from normal. Most notable were the high proportions of phospholipids and free cholesterol and the occurrence of the apoprotein E (arginine-rich protein) in remarkably high amounts especially in the abnormal HDL1-C.", "contents": "Characterization of high density lipoproteins in human cholestasis. High density lipoproteins (HDL) of plasma from patients with long-standing cholestasis were studied by several methods including crossed immunoelectrophoresis, gel filtration, and zonal ultracentrifugation. The crossed immunoelectrophoretic pattern against anti-HDL was characterized by the presence of several immunoprecipitates, in striking contrast to the pattern formed by normal HDL. One of these precipitates corresponded to a lipoprotein species dominated by apoprotein A-II (apo A-II). Zonal ultracentrifugation of cholestatic plasma showed a decrease of HDL and a disappearance of the normal delineation of HDL2 and HDL3. In addition a new component designated HDL1-C was observed. Consistent results were found at studies of the molecular size distribution of cholestatic HDL by gel filtration on Sephadex G-200. The lipid and apoprotein composition of isolated cholestatic HDL fractions differed considerably from normal. Most notable were the high proportions of phospholipids and free cholesterol and the occurrence of the apoprotein E (arginine-rich protein) in remarkably high amounts especially in the abnormal HDL1-C."}
{"id": "PMID:202015", "title": "Complement-dependent cytotoxicity against hepatoma cells mediated by IgM antibodies in serum from tumor-bearing rats.", "content": "Complement-dependent cytotoxic antibodies in syngeneic serum from rats carrying transplanted aminoazo dye-induced hepatomas (D23 and D33) and from rats immunized with irradiated tumor cell or homogenates were studied by a short-term 51Cr release assay. The tumor-bearer sera (TBS) were subjected to chromatography on unsolubilized protein A and Sepharose 4B. The cytolytic activity of D23 TBS was recovered in the IgM molecular weight region, whereas no such activity was obtained in the IgG fraction. As judged from immunodiffusion experiments, the IgM molecular weight fraction did not contain any aggregated or complexed IgG. Moreover, in immunofluorescence tests against viable hepatoma cells, using a specific anti-rat IgG conjugate, the TBS were negative. Cross-testing of D23 and D33 TBS against the two hepatomas and cross-absorption of the sera with tumor plasma membranes revealed no tumor specificity in these cytotoxicity reactions. Furthermore, neither fetal nor early postnatal liver cells could absorb out the activity. Absorptions with adult liver plasma membranes, however, abrogated the cytotoxic activity, and even more effective in this respect were homogenates from kidney and small intestine, thus indicating that the cytotoxic antibodies are directed against 'normal' adult antigen(s) present also in tissues other than liver.", "contents": "Complement-dependent cytotoxicity against hepatoma cells mediated by IgM antibodies in serum from tumor-bearing rats. Complement-dependent cytotoxic antibodies in syngeneic serum from rats carrying transplanted aminoazo dye-induced hepatomas (D23 and D33) and from rats immunized with irradiated tumor cell or homogenates were studied by a short-term 51Cr release assay. The tumor-bearer sera (TBS) were subjected to chromatography on unsolubilized protein A and Sepharose 4B. The cytolytic activity of D23 TBS was recovered in the IgM molecular weight region, whereas no such activity was obtained in the IgG fraction. As judged from immunodiffusion experiments, the IgM molecular weight fraction did not contain any aggregated or complexed IgG. Moreover, in immunofluorescence tests against viable hepatoma cells, using a specific anti-rat IgG conjugate, the TBS were negative. Cross-testing of D23 and D33 TBS against the two hepatomas and cross-absorption of the sera with tumor plasma membranes revealed no tumor specificity in these cytotoxicity reactions. Furthermore, neither fetal nor early postnatal liver cells could absorb out the activity. Absorptions with adult liver plasma membranes, however, abrogated the cytotoxic activity, and even more effective in this respect were homogenates from kidney and small intestine, thus indicating that the cytotoxic antibodies are directed against 'normal' adult antigen(s) present also in tissues other than liver."}
{"id": "PMID:202012", "title": "Cytochemistry--a tool in thyroid pathology.", "content": "The authors studied the cytoenzymic pattern of various thyropathies. The highest enzymic activity was found in Graves' disease, especially for peroxidase, glucose-6-phosphate dehydrogenase and succinate dehydrogenase. Lactate dehydrogenase showed a great activity in thyroid cancer. The lowest activity was found in Hashimoto's thyroiditis with strong fibrosclerosis. The cytophotometrical data in form of histograms showed dextro-deviation of curves and plurimodal, irregular aspects of nuclear volumes and nucleic acid content in agreement with the cytological features of the investigated thyropathies. The linear regression analysis between the nuclear volumes and the nucleic acid content disclosed a diminished correlation in thyroid carcinoma and in euthyroid goitre.", "contents": "Cytochemistry--a tool in thyroid pathology. The authors studied the cytoenzymic pattern of various thyropathies. The highest enzymic activity was found in Graves' disease, especially for peroxidase, glucose-6-phosphate dehydrogenase and succinate dehydrogenase. Lactate dehydrogenase showed a great activity in thyroid cancer. The lowest activity was found in Hashimoto's thyroiditis with strong fibrosclerosis. The cytophotometrical data in form of histograms showed dextro-deviation of curves and plurimodal, irregular aspects of nuclear volumes and nucleic acid content in agreement with the cytological features of the investigated thyropathies. The linear regression analysis between the nuclear volumes and the nucleic acid content disclosed a diminished correlation in thyroid carcinoma and in euthyroid goitre."}
{"id": "PMID:202016", "title": "Migration inhibition produced by sodium periodate oxidation of the macrophage membrane, and reversal by sodium borohydride.", "content": "Guinea pig peritoneal exudate cells were harvested 3 to 4 days after the intraperitoneal injection of Marcol oil. The washed cells were exposed to various concentrations of sodium periodate in phosphate-buffered saline (PBS) at pH 7.4 for 10 min at +4 degrees C. The cells were then used in the in vitro migration assay, and migration was consistently inhibited at concentrations from 10(-3) to 10(-5) M. The viability of the macrophages was not affected by this treatment. Sodium borohydride (10(-3) to 10(-5) M) in PBS for 10 min at pH 7.4 reversed the periodate effect. Experiments with purified macrophages showed that sodium periodate has a direct effect on macrophage function rather than an indirect effect via the potentiation of migration inhibition factor. In support of this, the in vitro spreading of macrophages on glass substrate for 1 h has been shown to be inhibited. This spreading inhibition can also be reversed by treatment with sodium borohydride. These results provide a new approach to understanding the biological significance and role of macrophage migration inhibition.", "contents": "Migration inhibition produced by sodium periodate oxidation of the macrophage membrane, and reversal by sodium borohydride. Guinea pig peritoneal exudate cells were harvested 3 to 4 days after the intraperitoneal injection of Marcol oil. The washed cells were exposed to various concentrations of sodium periodate in phosphate-buffered saline (PBS) at pH 7.4 for 10 min at +4 degrees C. The cells were then used in the in vitro migration assay, and migration was consistently inhibited at concentrations from 10(-3) to 10(-5) M. The viability of the macrophages was not affected by this treatment. Sodium borohydride (10(-3) to 10(-5) M) in PBS for 10 min at pH 7.4 reversed the periodate effect. Experiments with purified macrophages showed that sodium periodate has a direct effect on macrophage function rather than an indirect effect via the potentiation of migration inhibition factor. In support of this, the in vitro spreading of macrophages on glass substrate for 1 h has been shown to be inhibited. This spreading inhibition can also be reversed by treatment with sodium borohydride. These results provide a new approach to understanding the biological significance and role of macrophage migration inhibition."}
{"id": "PMID:202017", "title": "The inhibitory effect of coli-endotoxin on alpha-adrenergic receptor functions in the lower urinary tract. An in vitro study in cats.", "content": "The effects of endotoxin from E. coli 06 on alpha-adrenergic receptor functions have been investigated in muscle strips from the outlet region of the feline bladder. The endotoxin from this strain, known to cause urinary tract infections, inhibited the alpha-adrenergic contractions induced by phenylephrine and noradrenaline. This inhibition was dose-dependent, correlated to time of exposure, and reversible. Alpha-adrenergic receptor function in muscle strips from cat aorta was also inhibited, but not cholinergic stimulation of muscle segments from the bladder.", "contents": "The inhibitory effect of coli-endotoxin on alpha-adrenergic receptor functions in the lower urinary tract. An in vitro study in cats. The effects of endotoxin from E. coli 06 on alpha-adrenergic receptor functions have been investigated in muscle strips from the outlet region of the feline bladder. The endotoxin from this strain, known to cause urinary tract infections, inhibited the alpha-adrenergic contractions induced by phenylephrine and noradrenaline. This inhibition was dose-dependent, correlated to time of exposure, and reversible. Alpha-adrenergic receptor function in muscle strips from cat aorta was also inhibited, but not cholinergic stimulation of muscle segments from the bladder."}
{"id": "PMID:202018", "title": "Adult nephroblastoma.", "content": "A case of adult nephroblastoma in a 51-year-old woman is reported. A percutaneous aspiration biopsy did not lead to the right diagnosis presumably because the histologic structure of the tumour consisted exclusively of more or less differentiated epithelial-like elements, while mesenchymal tumour components were not demonstrated. It is concluded that this type of nephroblastoma, resembling a renal adenocarcinoma, should be borne in mind with a view to an optimal postoperative treatment.", "contents": "Adult nephroblastoma. A case of adult nephroblastoma in a 51-year-old woman is reported. A percutaneous aspiration biopsy did not lead to the right diagnosis presumably because the histologic structure of the tumour consisted exclusively of more or less differentiated epithelial-like elements, while mesenchymal tumour components were not demonstrated. It is concluded that this type of nephroblastoma, resembling a renal adenocarcinoma, should be borne in mind with a view to an optimal postoperative treatment."}
{"id": "PMID:202019", "title": "Primary bronchial carcioma. An analysis of lung operations performed at Kolding hospital during the 10-year period 1965--1974.", "content": "A clinical material consisting of 88 patients with primary bronchial carcinoma, treated at the Department of General Surgery, Kolding Hospital, during the 10-year period 1965--1974, is presented. It was possible to operate on 98% of the patients. Resection was performed in 76%: 75% as pneumonectomies and 25% as lobectomies. All the operations were performed by the same surgeon. The 5-year survival rates for the total number of patients were 19% during the period 1965--69 and 22% during the period 1970--74. The survival rates after resection were 26% and 28%, respectively, during the same periods. On the basis of the above-mentioned material and results, it may be concluded that an operation such as resection of the lung can be performed with the same degree of safety in operating theatres other than those of departments of thoracic surgery.", "contents": "Primary bronchial carcioma. An analysis of lung operations performed at Kolding hospital during the 10-year period 1965--1974. A clinical material consisting of 88 patients with primary bronchial carcinoma, treated at the Department of General Surgery, Kolding Hospital, during the 10-year period 1965--1974, is presented. It was possible to operate on 98% of the patients. Resection was performed in 76%: 75% as pneumonectomies and 25% as lobectomies. All the operations were performed by the same surgeon. The 5-year survival rates for the total number of patients were 19% during the period 1965--69 and 22% during the period 1970--74. The survival rates after resection were 26% and 28%, respectively, during the same periods. On the basis of the above-mentioned material and results, it may be concluded that an operation such as resection of the lung can be performed with the same degree of safety in operating theatres other than those of departments of thoracic surgery."}
{"id": "PMID:202020", "title": "[Therapeutic results using VP 16-213 alone or in combination with 5-fluorouracil in liver cancer (hepatoma)].", "content": "The podophyllotoxin derivative VP 16-213 was used as monotherapy in 6 patients and combined with 5-fluorouracil in another 6. Of the 12 patients treated, 11 had measurable tumor criteria and 5 of these responded to treatment. These responses were attributed mainly to the effects of VP 16-213. Patients responding to chemotherapy lived significantly longer than non-responders. Each case of objective tumor response was accompanied by subjective improvement. In view of these results, a more active approach to the treatment of hepatocellular carcinoma would seem to be justified.", "contents": "[Therapeutic results using VP 16-213 alone or in combination with 5-fluorouracil in liver cancer (hepatoma)]. The podophyllotoxin derivative VP 16-213 was used as monotherapy in 6 patients and combined with 5-fluorouracil in another 6. Of the 12 patients treated, 11 had measurable tumor criteria and 5 of these responded to treatment. These responses were attributed mainly to the effects of VP 16-213. Patients responding to chemotherapy lived significantly longer than non-responders. Each case of objective tumor response was accompanied by subjective improvement. In view of these results, a more active approach to the treatment of hepatocellular carcinoma would seem to be justified."}
{"id": "PMID:202022", "title": "Assembly of type C oncornaviruses: a model.", "content": "The salient features of this model for oncornavirus assembly are that uncleaved precursor molecules to the internal virus polypeptides possess specific recognition sites both for viral envelope constituents already inserted in the cell membrane and for the viral RNA. After orderly alignment of these components at the budding site, virus maturation proceeds through specific proteolytic cleavage of the precursor components and association of the resultant molecules into the characteristic type C virion substructures revealed by electron microscopy.", "contents": "Assembly of type C oncornaviruses: a model. The salient features of this model for oncornavirus assembly are that uncleaved precursor molecules to the internal virus polypeptides possess specific recognition sites both for viral envelope constituents already inserted in the cell membrane and for the viral RNA. After orderly alignment of these components at the budding site, virus maturation proceeds through specific proteolytic cleavage of the precursor components and association of the resultant molecules into the characteristic type C virion substructures revealed by electron microscopy."}
{"id": "PMID:202023", "title": "Intercellular communication in insect development is hormonally controlled.", "content": "Cellular coupling in the insect epidermis changes in a characteristic way during metamorphosis. In vitro, beta-ecdysone mimics the initial phase of these changes by increasing electrical coupling. Both adenosine 3',5'-monophosphate (cyclic AMP) and Ca2+ reverse natural and beta-ecdysone-stimulated changes, which suggests that ecdysone could work on communication through changes in cyclic AMP and Ca2+ levels. The transient changes in intercellular communication before metamorphosis may reflect the timing of the signals that trigger proliferation and the generation of new spatial patterns in the epidermis.", "contents": "Intercellular communication in insect development is hormonally controlled. Cellular coupling in the insect epidermis changes in a characteristic way during metamorphosis. In vitro, beta-ecdysone mimics the initial phase of these changes by increasing electrical coupling. Both adenosine 3',5'-monophosphate (cyclic AMP) and Ca2+ reverse natural and beta-ecdysone-stimulated changes, which suggests that ecdysone could work on communication through changes in cyclic AMP and Ca2+ levels. The transient changes in intercellular communication before metamorphosis may reflect the timing of the signals that trigger proliferation and the generation of new spatial patterns in the epidermis."}
{"id": "PMID:202024", "title": "Tricyclic antidepressants: therapeutic properties and affinity for alpha-noradrenergic receptor binding sites in the brain.", "content": "Tricyclic antidepressants vary in their capacity to cause psychomotor activation, to relieve agitated depressive states, and to cause sedation and hypotension. We have quantified relative potencies of tricyclic antidepressants in competing for the binding of 3H-labeled WB-4101 to alpha-noradrenergic receptor sites in rat brain membranes. Affinities of tricyclic drugs for alpha-noradrenergic receptor sites in the brain correlate well with the capacity of these agents to relieve psychomotor agitation and to induce sedation and hypotension; these affinities also correlate inversely with tendencies to elicit psychomotor activation.", "contents": "Tricyclic antidepressants: therapeutic properties and affinity for alpha-noradrenergic receptor binding sites in the brain. Tricyclic antidepressants vary in their capacity to cause psychomotor activation, to relieve agitated depressive states, and to cause sedation and hypotension. We have quantified relative potencies of tricyclic antidepressants in competing for the binding of 3H-labeled WB-4101 to alpha-noradrenergic receptor sites in rat brain membranes. Affinities of tricyclic drugs for alpha-noradrenergic receptor sites in the brain correlate well with the capacity of these agents to relieve psychomotor agitation and to induce sedation and hypotension; these affinities also correlate inversely with tendencies to elicit psychomotor activation."}
{"id": "PMID:202025", "title": "Intracellular analysis of trigeminal motoneuron activity during sleep in the cat.", "content": "Intracellular recordings were made from trigeminal motoneurons of normally respiring, unanesthetized cats during naturally occurring sleep. The transition from quiet to active sleep was accompanied by tonic motoneuron hyperpolarization. Stimulation of the reticular formation induced a depolarizing potential in trigeminal motoneurons during quiet sleep and a hyperpolarizing potential during active sleep. The results provide a synaptic explanation for the phenomenon of reticular response reversal and insights into the basic mechanisms controlling motor activity during the sleep states.", "contents": "Intracellular analysis of trigeminal motoneuron activity during sleep in the cat. Intracellular recordings were made from trigeminal motoneurons of normally respiring, unanesthetized cats during naturally occurring sleep. The transition from quiet to active sleep was accompanied by tonic motoneuron hyperpolarization. Stimulation of the reticular formation induced a depolarizing potential in trigeminal motoneurons during quiet sleep and a hyperpolarizing potential during active sleep. The results provide a synaptic explanation for the phenomenon of reticular response reversal and insights into the basic mechanisms controlling motor activity during the sleep states."}
{"id": "PMID:202026", "title": "Particle-mediated membrane uptake of chemical carcinogens studied by fluorescence spectroscopy.", "content": "The fluorescence emissions of chrysene, N-ethylcarbazole, and 1,6-diphenylhexatriene undergo large spectral shifts or changes in quantum yield, or both, upon their uptake from particulates by phospholipid vesicles. This membrane uptake of carcinogen and carcinogen-like molecules by model membranes does not result in any disruption of the lipid bilayers. The fluorescence emission of chrysene, when bound to silica, was found to be sensitive to the surface density of chrysene on the silica. These observations demonstrate the feasibility of using fluorescence spectroscopy to measure the rates of exchange of carcinogens from particulate matter to cell membranes and to characterize the surface distribution of chemical carcinogens on particulate matter. Comparison of the uptake rate of chrysene from the unperturbed crystal state, sonicated crystals, and the silica-adsorbed state demonstrated that the last condition results in the most rapid transport of chrysene into model membranes. This information should prove valuable in understanding the cocarcinogenic effects of particulates and polynuclear aromatic hydrocarbons.", "contents": "Particle-mediated membrane uptake of chemical carcinogens studied by fluorescence spectroscopy. The fluorescence emissions of chrysene, N-ethylcarbazole, and 1,6-diphenylhexatriene undergo large spectral shifts or changes in quantum yield, or both, upon their uptake from particulates by phospholipid vesicles. This membrane uptake of carcinogen and carcinogen-like molecules by model membranes does not result in any disruption of the lipid bilayers. The fluorescence emission of chrysene, when bound to silica, was found to be sensitive to the surface density of chrysene on the silica. These observations demonstrate the feasibility of using fluorescence spectroscopy to measure the rates of exchange of carcinogens from particulate matter to cell membranes and to characterize the surface distribution of chemical carcinogens on particulate matter. Comparison of the uptake rate of chrysene from the unperturbed crystal state, sonicated crystals, and the silica-adsorbed state demonstrated that the last condition results in the most rapid transport of chrysene into model membranes. This information should prove valuable in understanding the cocarcinogenic effects of particulates and polynuclear aromatic hydrocarbons."}
{"id": "PMID:202027", "title": "Pineal serotonin N-acetyltransferase activity: abrupt decrease in adenosine 3',5'-monophosphate may be signal for \"turnoff\".", "content": "Dispersed pinealocytes have been used to study the role of adenosine 3',5'-monophosphate (cyclic AMP) in the \"turnoff\" of N-acetyltransferace activity. Activity was first stimulated 100-fold by treating cells with 1-norepinephrine. 1-Propranolol acted stereospecifically to rapidly reverse this, resulting in a 70 percent loss of enzyme activity within 15 minutes. An even more rapid 1-propranolol-induced decreased in cyclic AMP also occurred. This together with the observation that the inhibitory effect of 1-propranolol on N-acetyltransferase was blocked by dibutyryl cyclic AMP and phosphodiesterase inhibitors indicate that an abrupt decrease in cyclic AMP may be the signal for the rapid decrease in pineal N-acetyltransferase activity.", "contents": "Pineal serotonin N-acetyltransferase activity: abrupt decrease in adenosine 3',5'-monophosphate may be signal for \"turnoff\". Dispersed pinealocytes have been used to study the role of adenosine 3',5'-monophosphate (cyclic AMP) in the \"turnoff\" of N-acetyltransferace activity. Activity was first stimulated 100-fold by treating cells with 1-norepinephrine. 1-Propranolol acted stereospecifically to rapidly reverse this, resulting in a 70 percent loss of enzyme activity within 15 minutes. An even more rapid 1-propranolol-induced decreased in cyclic AMP also occurred. This together with the observation that the inhibitory effect of 1-propranolol on N-acetyltransferase was blocked by dibutyryl cyclic AMP and phosphodiesterase inhibitors indicate that an abrupt decrease in cyclic AMP may be the signal for the rapid decrease in pineal N-acetyltransferase activity."}
{"id": "PMID:202028", "title": "Regulatory role of guanosine 3',5'-monophosphate in adrenocorticotropin hormone-induced steroidogenesis.", "content": "The relation between steroidogenesis induced by adrenocorticotropic hormone and the concentrations of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) was studied at different time intervals in isolated adrenal cells. Submaximal and supramaximal steroidogenic concentrations of the hormone did not cause detectable changes in cyclic AMP during the first 30 minutes, whereas there was an increase in the concentration of cyclic GMP that was accompanied by phosphorylation and steroidogenesis. It is therefore suggested that cyclic GMP, rather than cyclic AMP, is the physiological mediator of adrenocorticotropic hormone-induced adrenal steroidogenesis.", "contents": "Regulatory role of guanosine 3',5'-monophosphate in adrenocorticotropin hormone-induced steroidogenesis. The relation between steroidogenesis induced by adrenocorticotropic hormone and the concentrations of adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) was studied at different time intervals in isolated adrenal cells. Submaximal and supramaximal steroidogenic concentrations of the hormone did not cause detectable changes in cyclic AMP during the first 30 minutes, whereas there was an increase in the concentration of cyclic GMP that was accompanied by phosphorylation and steroidogenesis. It is therefore suggested that cyclic GMP, rather than cyclic AMP, is the physiological mediator of adrenocorticotropic hormone-induced adrenal steroidogenesis."}
{"id": "PMID:202029", "title": "Guanosine 3',5'-monophosphate: a central nervous system regulator of analgesia.", "content": "The dibutyryl derivative of guanosine 3',5'-monophosphate (cyclic GMP), administered centrally, totally abolishes response to noxious stimuli without depressing the central nervous system. Analgesic properties of the nucleotide are not reversed by naloxone. Microinjected intracerebrally into different sites, dibutyryl cyclic GMP does not mimic the action of morphine. Pharmacological effects of dibutyryl cyclic GMP suggest that endogenous cyclic GMP modulates an inhibitory pain pathway distinct from that on which morphine acts.", "contents": "Guanosine 3',5'-monophosphate: a central nervous system regulator of analgesia. The dibutyryl derivative of guanosine 3',5'-monophosphate (cyclic GMP), administered centrally, totally abolishes response to noxious stimuli without depressing the central nervous system. Analgesic properties of the nucleotide are not reversed by naloxone. Microinjected intracerebrally into different sites, dibutyryl cyclic GMP does not mimic the action of morphine. Pharmacological effects of dibutyryl cyclic GMP suggest that endogenous cyclic GMP modulates an inhibitory pain pathway distinct from that on which morphine acts."}
{"id": "PMID:202031", "title": "Maternal behavior as a regulator of polyamine biosynthesis in brain and heart of the developing rat pup.", "content": "Rat pups removed from the mother and placed in a warm incubator for 1 hour or more show a 50 percent reduction in ornithine decarboxylase activity in the brain and heart. The decline is not caused by lack of nutrition. Instead, these studies suggest that active maternal behavior is necessary to maintain normal polyamine metabolism in brain and heart of the pup during development.", "contents": "Maternal behavior as a regulator of polyamine biosynthesis in brain and heart of the developing rat pup. Rat pups removed from the mother and placed in a warm incubator for 1 hour or more show a 50 percent reduction in ornithine decarboxylase activity in the brain and heart. The decline is not caused by lack of nutrition. Instead, these studies suggest that active maternal behavior is necessary to maintain normal polyamine metabolism in brain and heart of the pup during development."}
{"id": "PMID:202032", "title": "Pentobarbital: differential postsynaptic actions on sympathetic ganglion cells.", "content": "The frog sympathetic ganglion has been used as a model to elucidate the cellular mechanism of barbiturate anesthesia. Anesthetic concentrations of pentobarbital markedly reduced the fast nicotinic excitatory postsynaptic potential while having no effect on the slow excitatory postsynaptic potential or slow inhibitory postsynaptic potential, even though all three synaptic potentials depend on the presynaptic release of acetylcholine. A similar differential effect was seen for nicotinic and muscarinic responses to exogenously applied agonists, while the depolarizing action of gamma-aminobutyric acid (GABA) was enhanced. These results indicate that pentobarbital has remarkably selective actions on the sympathetic ganglion and further indicate that blockade of ganglionic transmission by anesthetic concentrations of pentobarbital can be entirely explained by a postsynaptic action. The present results strengthen the concept that pentobarbital anesthesia results from a postsynaptic blockade of central excitatory synapses which increase sodium conductance coupled with a postsynaptic enhancement of GABA-mediated synaptic inhibition.", "contents": "Pentobarbital: differential postsynaptic actions on sympathetic ganglion cells. The frog sympathetic ganglion has been used as a model to elucidate the cellular mechanism of barbiturate anesthesia. Anesthetic concentrations of pentobarbital markedly reduced the fast nicotinic excitatory postsynaptic potential while having no effect on the slow excitatory postsynaptic potential or slow inhibitory postsynaptic potential, even though all three synaptic potentials depend on the presynaptic release of acetylcholine. A similar differential effect was seen for nicotinic and muscarinic responses to exogenously applied agonists, while the depolarizing action of gamma-aminobutyric acid (GABA) was enhanced. These results indicate that pentobarbital has remarkably selective actions on the sympathetic ganglion and further indicate that blockade of ganglionic transmission by anesthetic concentrations of pentobarbital can be entirely explained by a postsynaptic action. The present results strengthen the concept that pentobarbital anesthesia results from a postsynaptic blockade of central excitatory synapses which increase sodium conductance coupled with a postsynaptic enhancement of GABA-mediated synaptic inhibition."}
{"id": "PMID:202034", "title": "Nelson's syndrome: case report and review of the literature.", "content": "A patient who developed a pituitary tumor after adrenalectomy for Cushing's disease (Nelson's syndrome) is presented. The literature reviewed shows less than a 10 percent incidence of this disorder for which extremely elevated plasma ACTH levels are diagnostic. Special radiologic technics may be required to detect small pituitary tumors, but pituitary hormone levels may be elevated in the cerebrospinal fluid if there is suprasellar tumor extension. The different modalities available for treatment of Nelson's syndrome are discussed.", "contents": "Nelson's syndrome: case report and review of the literature. A patient who developed a pituitary tumor after adrenalectomy for Cushing's disease (Nelson's syndrome) is presented. The literature reviewed shows less than a 10 percent incidence of this disorder for which extremely elevated plasma ACTH levels are diagnostic. Special radiologic technics may be required to detect small pituitary tumors, but pituitary hormone levels may be elevated in the cerebrospinal fluid if there is suprasellar tumor extension. The different modalities available for treatment of Nelson's syndrome are discussed."}
{"id": "PMID:202035", "title": "Visceral leishmaniasis acquired in Greece: diagnosis and treatment in an American child.", "content": "Reported is a case of visceral leishmaniasis acquired in Greece by a 3-year-old American child. Untreated, this protozoan infection causes a high mortality. Specific treatment is available, making early recognition of the illness important. This child's infection responded dramatically to a course of sodium antimony gluconate. Repeat bone marrow cultures demonstrated persistent organisms and a second course of treatment was required. Monitoring of his response to therapy suggested that serial bone marrow cultures and the neutrophil response may be sensitive means for following the course of this infection.", "contents": "Visceral leishmaniasis acquired in Greece: diagnosis and treatment in an American child. Reported is a case of visceral leishmaniasis acquired in Greece by a 3-year-old American child. Untreated, this protozoan infection causes a high mortality. Specific treatment is available, making early recognition of the illness important. This child's infection responded dramatically to a course of sodium antimony gluconate. Repeat bone marrow cultures demonstrated persistent organisms and a second course of treatment was required. Monitoring of his response to therapy suggested that serial bone marrow cultures and the neutrophil response may be sensitive means for following the course of this infection."}
{"id": "PMID:202036", "title": "Hypothalamo-pituitary-adrenal function in pituitary adenoma and craniopharyngioma. Part I: Insulin test, lysine-vasopressin test, and rapid ACTH test.", "content": "For the assessment of hypothalamo-pituitary-adrenal function in the presence of pituitary adenomas and craniopharyngiomas, insulin tests, lysine-vasopressin tests, and rapid ACTH tests were performed and plasma cortisol was assayed. Rapid ACTH test and lysine-vasopressin test, which examine adrenal and mainly pituitary function respectively, showed normal function in ten among 14 cases. But insulin test, which examines the whole hypothalamo-pituitary-adrenal function, showed various levels of abnormality in eight among 14 cases. Frequent association of functional disturbances of this axis in these diseases was stressed.", "contents": "Hypothalamo-pituitary-adrenal function in pituitary adenoma and craniopharyngioma. Part I: Insulin test, lysine-vasopressin test, and rapid ACTH test. For the assessment of hypothalamo-pituitary-adrenal function in the presence of pituitary adenomas and craniopharyngiomas, insulin tests, lysine-vasopressin tests, and rapid ACTH tests were performed and plasma cortisol was assayed. Rapid ACTH test and lysine-vasopressin test, which examine adrenal and mainly pituitary function respectively, showed normal function in ten among 14 cases. But insulin test, which examines the whole hypothalamo-pituitary-adrenal function, showed various levels of abnormality in eight among 14 cases. Frequent association of functional disturbances of this axis in these diseases was stressed."}
{"id": "PMID:202037", "title": "False positive complement fixation tests with respiratory virus preparations in bird fanciers with allergic alveolitis.", "content": "False positive raised complement fixation titres to egg-grown virus preparations were found in six pigeon fanciers suffering from extrinsic allergic alveolitis but not in six similar budgerigar fanciers. The raised titres in the pigeon fanciers fell fourfold over a short interval in the absence of avian exposure and were attributable to antibodies directed against antigens from hen's egg in which the test virus preparations were grown. Such antigens were shown to be present in the virus preparations. In view of the clinical similarities between influenza and acute extrinsic allergic alveolitis, it is essential that a diagnosis of influenza in bird fanciers is not based on either a single raised titre or a fourfold fall in complement fixation titre without appropriate control tests with avian antigens.", "contents": "False positive complement fixation tests with respiratory virus preparations in bird fanciers with allergic alveolitis. False positive raised complement fixation titres to egg-grown virus preparations were found in six pigeon fanciers suffering from extrinsic allergic alveolitis but not in six similar budgerigar fanciers. The raised titres in the pigeon fanciers fell fourfold over a short interval in the absence of avian exposure and were attributable to antibodies directed against antigens from hen's egg in which the test virus preparations were grown. Such antigens were shown to be present in the virus preparations. In view of the clinical similarities between influenza and acute extrinsic allergic alveolitis, it is essential that a diagnosis of influenza in bird fanciers is not based on either a single raised titre or a fourfold fall in complement fixation titre without appropriate control tests with avian antigens."}
{"id": "PMID:202038", "title": "Effects of prostaglandins, derivatives of cyclic 3':5'-AMP, theophylline, cholinergic agents and colchicine on clot retraction in dilute platelet-rich plasma and gel-separated platelet test systems.", "content": "In dilute suspensions of platelet-rich plasma (PRP) or gel-separated platelets (GSP), dibutyryl-cAMP (DBcAMP) and monobutyryl-cAMP inhibited platelet-mediated fibrin clot retraction in concentrations of 2--3 X 10(-6) M, with complete inhibition at 1--3 X 10(-4) M. Prostaglandin E1 (PGE1), which inhibited fibrin clot retraction in concentrations greater than 1.5--3 X 10(-8) M, was a more effective inhibitor than either PGE2 or PGF2 alpha. In the presence of theophylline (10-4 M), concentrations of DBcAMP, PGE1, PGE2 and PGF2 alpha necessary to inhibit fibrin clot retraction were reduced 50-fold for DBcAMP and 2.5 to 20-fold for the prostaglandins. In dilute PRP or GSP, inhibition of fibrin clot retraction does not result from inhibition of thrombin-induced platelet aggregation. Thus, compounds which increase platelet cAMP levels result in the inhibition of platelet-mediated fibrin clot retraction, and this inhibitory effect may be mediated, at least in part, through suppression of platelet contractility. Cyclic GMP, dibutyryl-cGMP and carbamylcholine-Cl (which stimulate guanylate cyclase) did not influence fibrin clot retraction, and did not prevent inhibition of fibrin clot retraction by DBcAMP and PGE1. Colchicine, in concentrations known to disrupt platelet microtubules (2.5 X 10(-6) M to 2.5 X 10(-3) M), had little inhibitory effect on either fibrin clot retraction or platelet (3H)-serotonin release.", "contents": "Effects of prostaglandins, derivatives of cyclic 3':5'-AMP, theophylline, cholinergic agents and colchicine on clot retraction in dilute platelet-rich plasma and gel-separated platelet test systems. In dilute suspensions of platelet-rich plasma (PRP) or gel-separated platelets (GSP), dibutyryl-cAMP (DBcAMP) and monobutyryl-cAMP inhibited platelet-mediated fibrin clot retraction in concentrations of 2--3 X 10(-6) M, with complete inhibition at 1--3 X 10(-4) M. Prostaglandin E1 (PGE1), which inhibited fibrin clot retraction in concentrations greater than 1.5--3 X 10(-8) M, was a more effective inhibitor than either PGE2 or PGF2 alpha. In the presence of theophylline (10-4 M), concentrations of DBcAMP, PGE1, PGE2 and PGF2 alpha necessary to inhibit fibrin clot retraction were reduced 50-fold for DBcAMP and 2.5 to 20-fold for the prostaglandins. In dilute PRP or GSP, inhibition of fibrin clot retraction does not result from inhibition of thrombin-induced platelet aggregation. Thus, compounds which increase platelet cAMP levels result in the inhibition of platelet-mediated fibrin clot retraction, and this inhibitory effect may be mediated, at least in part, through suppression of platelet contractility. Cyclic GMP, dibutyryl-cGMP and carbamylcholine-Cl (which stimulate guanylate cyclase) did not influence fibrin clot retraction, and did not prevent inhibition of fibrin clot retraction by DBcAMP and PGE1. Colchicine, in concentrations known to disrupt platelet microtubules (2.5 X 10(-6) M to 2.5 X 10(-3) M), had little inhibitory effect on either fibrin clot retraction or platelet (3H)-serotonin release."}
{"id": "PMID:202045", "title": "The epidemiology of infection with Entamoeba histolytica in the Gambia, West Africa.", "content": "A country-wide stool survey of The Gambia showed the prevalence of Entamoeba histolytica cysts to range from 13.7% up-country in the dry season to 52.3% near the coast. A longitudinal survey showed a near 100% infection rate over one year and a sharp rise in prevalence as the rains commence with an equally sharp fall as the rains progress. Specific antibody levels are elevated and reasonably constant through the year. Carriers generally show no specific lymphocyte reactivity to amoebic antigen but consistently parasite-negative individuals tended to show elevated lymphocyte reactivity. Attempts to discover the presence of cysts in the environment of villages by cultivation of specimens of water, soil, food, flies and washing from clothes and hands generally failed though E. histolytica was recovered once from a well.", "contents": "The epidemiology of infection with Entamoeba histolytica in the Gambia, West Africa. A country-wide stool survey of The Gambia showed the prevalence of Entamoeba histolytica cysts to range from 13.7% up-country in the dry season to 52.3% near the coast. A longitudinal survey showed a near 100% infection rate over one year and a sharp rise in prevalence as the rains commence with an equally sharp fall as the rains progress. Specific antibody levels are elevated and reasonably constant through the year. Carriers generally show no specific lymphocyte reactivity to amoebic antigen but consistently parasite-negative individuals tended to show elevated lymphocyte reactivity. Attempts to discover the presence of cysts in the environment of villages by cultivation of specimens of water, soil, food, flies and washing from clothes and hands generally failed though E. histolytica was recovered once from a well."}
{"id": "PMID:202048", "title": "The relationship between hepatitis B virus infection and hepatic cell carcinoma in Mozambique.", "content": "Hepatitis B surface antigen and antibody were sought in sera collected from patients with hepatic cell carcinoma and from healthy blood donors. The frequency of the antigen among the patients was significantly higher than that among blood donors who served as controls (p = less than .01) but no significant difference was found in estimated exposure to hepatitis B virus between hepatic cell carcinoma patients and African blood donors. However, exposure to hepatitis B virus was significantly less frequent (p = less than .01) among European blood donors when compared to African blood donors.", "contents": "The relationship between hepatitis B virus infection and hepatic cell carcinoma in Mozambique. Hepatitis B surface antigen and antibody were sought in sera collected from patients with hepatic cell carcinoma and from healthy blood donors. The frequency of the antigen among the patients was significantly higher than that among blood donors who served as controls (p = less than .01) but no significant difference was found in estimated exposure to hepatitis B virus between hepatic cell carcinoma patients and African blood donors. However, exposure to hepatitis B virus was significantly less frequent (p = less than .01) among European blood donors when compared to African blood donors."}
{"id": "PMID:202049", "title": "Experimental infection of Nigerian sheep and goats with bovine virus diarrhoea virus.", "content": "Apart from leucopenia and a low grade pyrexia Nigerian goats showed no ill effects following inoculation with bovine virus diarrhoea virus. Sheep showed a variable leucopenia without pyrexia. No difficulty should arise in differentiating BVD infections from peste des petits ruminants.", "contents": "Experimental infection of Nigerian sheep and goats with bovine virus diarrhoea virus. Apart from leucopenia and a low grade pyrexia Nigerian goats showed no ill effects following inoculation with bovine virus diarrhoea virus. Sheep showed a variable leucopenia without pyrexia. No difficulty should arise in differentiating BVD infections from peste des petits ruminants."}
{"id": "PMID:202064", "title": "[Test of an attenuated viral strain of TGE as a vaccine].", "content": "A live vaccine was produced using a local strain P of the virus of the transmissive gastroenteritis, arrenuated in cell cultures. The vaccinated pregnant sows had high-titer serum and colostrum virus-neutralizing antibodies. In the first days following farrowing there were in the colostrum ummunoglobulins of the Igg class that prevailed, however, IgA and IgM proved more effective in the virus-neutralizing test. Newborn pigs acquired passive immunity at about the 24th hour after the intake of colostrum. They withstood a challenge with a virulent virus.", "contents": "[Test of an attenuated viral strain of TGE as a vaccine]. A live vaccine was produced using a local strain P of the virus of the transmissive gastroenteritis, arrenuated in cell cultures. The vaccinated pregnant sows had high-titer serum and colostrum virus-neutralizing antibodies. In the first days following farrowing there were in the colostrum ummunoglobulins of the Igg class that prevailed, however, IgA and IgM proved more effective in the virus-neutralizing test. Newborn pigs acquired passive immunity at about the 24th hour after the intake of colostrum. They withstood a challenge with a virulent virus."}
{"id": "PMID:202065", "title": "[Serological response of rabbits following immunization with M. parainfluenzae-3, adenovirus I and infectious bovine rhinotracheitis virus associated antigens].", "content": "The immunization of rabbits separately with virus suspensions of Myxovirus parainfluenzae-3, adenovirus serotype I, and bovine rhinotracheitis virus or with combinations of each two of them and with a combination of all three viruses led to the production of sera having titers of virus-neutralizing antibodies acting against each of the antigens that participated in the combination. Results showed that no inhibition existed of the antigens during immunization as established by the serologic response of the rabbits. The demonstrated specificity of the monovalent sera points to the fact that the latter could be used for the diagnostic purposes.", "contents": "[Serological response of rabbits following immunization with M. parainfluenzae-3, adenovirus I and infectious bovine rhinotracheitis virus associated antigens]. The immunization of rabbits separately with virus suspensions of Myxovirus parainfluenzae-3, adenovirus serotype I, and bovine rhinotracheitis virus or with combinations of each two of them and with a combination of all three viruses led to the production of sera having titers of virus-neutralizing antibodies acting against each of the antigens that participated in the combination. Results showed that no inhibition existed of the antigens during immunization as established by the serologic response of the rabbits. The demonstrated specificity of the monovalent sera points to the fact that the latter could be used for the diagnostic purposes."}
{"id": "PMID:202066", "title": "[Use of the plaque method for isolating Aujeszky's disease virus from meat, organs and meat products].", "content": "Comparative virologic studies were carried out to isolate the virus of Aujesky's disease from meat, viscera, and raw smoked products by the plaque method as modified by Sullivan and Read as well as by the method with which the presence of the virus is recorded visually by the cytopathic effect observed in the infected cell monolayer. It was found that at the veterinary and sanitary inspection of meat and meat products produced from diseases or survived animals the modified plaque method proved more suitable as against the other method. The former made it possible to determine directly and at low titers the virus of Aujeszky's disease for the needs of research and practical activities associated with rendering the meat harmless as coming from diseased pigs.", "contents": "[Use of the plaque method for isolating Aujeszky's disease virus from meat, organs and meat products]. Comparative virologic studies were carried out to isolate the virus of Aujesky's disease from meat, viscera, and raw smoked products by the plaque method as modified by Sullivan and Read as well as by the method with which the presence of the virus is recorded visually by the cytopathic effect observed in the infected cell monolayer. It was found that at the veterinary and sanitary inspection of meat and meat products produced from diseases or survived animals the modified plaque method proved more suitable as against the other method. The former made it possible to determine directly and at low titers the virus of Aujeszky's disease for the needs of research and practical activities associated with rendering the meat harmless as coming from diseased pigs."}
{"id": "PMID:202067", "title": "Degenerative processes in the pathogenesis of pulmonary alveolar lipoproteinosis.", "content": "Electron microscopy in an infant of 4 months with pulmonary alveolar lipoproteinosis showed filling of the alveoli with osmiophilic lamellar bodies. Similar structures were present in the cytoplasm of type I alveolar epithelial cells and to a lesser extent in the capillary endothelium and interstitium. These changes represent widespread degenerative processes in the lung caused by an unidentified cytotoxic agent. In this patient the disease is comparable to the drug-induced cytotoxic animal model and differs from the dust-induced hypersecretory animal model.", "contents": "Degenerative processes in the pathogenesis of pulmonary alveolar lipoproteinosis. Electron microscopy in an infant of 4 months with pulmonary alveolar lipoproteinosis showed filling of the alveoli with osmiophilic lamellar bodies. Similar structures were present in the cytoplasm of type I alveolar epithelial cells and to a lesser extent in the capillary endothelium and interstitium. These changes represent widespread degenerative processes in the lung caused by an unidentified cytotoxic agent. In this patient the disease is comparable to the drug-induced cytotoxic animal model and differs from the dust-induced hypersecretory animal model."}
{"id": "PMID:202068", "title": "Further observations on the relationship between the matrix and the calcifying fronts in osteosarcoma.", "content": "Human osteosarcoma biopsies were studied with the SEM using sequential etching with sodium hypochlorite solutions after removal of aluminium or gold coatings. Osteosarcomas differ from normal hard tissues in that the matrix never proceeds to complete mineralization, so that the specimens fragment on hypochlorite treatment. Details of the fibrillar pattern and calcospheritic type of mineralization pattern can be seen in hypochlorite etched, fractured surfaces and mineralizing fronts.", "contents": "Further observations on the relationship between the matrix and the calcifying fronts in osteosarcoma. Human osteosarcoma biopsies were studied with the SEM using sequential etching with sodium hypochlorite solutions after removal of aluminium or gold coatings. Osteosarcomas differ from normal hard tissues in that the matrix never proceeds to complete mineralization, so that the specimens fragment on hypochlorite treatment. Details of the fibrillar pattern and calcospheritic type of mineralization pattern can be seen in hypochlorite etched, fractured surfaces and mineralizing fronts."}
{"id": "PMID:202069", "title": "Benign epithelial nephroblastoma. A contribution to its histogenesis.", "content": "The occurrence of a malignant Wilms'tumor in the right kidney and of a benign epithelial nephroblastoma in the left kidney of a 5-year-old girl is reported. Both kidneys contained foci of persistent well differentiated blastema. In the left kidney a direct transformation of the primitive metanephric epithelium into a benign nephroblastoma is shown. This finding suggests an origin of epithelial nephroblastoma from persistent nephrogenic tissue and indicates that the former represents the benign counterpart of the malignant Wilms'tumor.", "contents": "Benign epithelial nephroblastoma. A contribution to its histogenesis. The occurrence of a malignant Wilms'tumor in the right kidney and of a benign epithelial nephroblastoma in the left kidney of a 5-year-old girl is reported. Both kidneys contained foci of persistent well differentiated blastema. In the left kidney a direct transformation of the primitive metanephric epithelium into a benign nephroblastoma is shown. This finding suggests an origin of epithelial nephroblastoma from persistent nephrogenic tissue and indicates that the former represents the benign counterpart of the malignant Wilms'tumor."}
{"id": "PMID:202070", "title": "[Paget's disease of bone: ultrastructure and cytogenesis of osteoclasts (author's transl)].", "content": "The cytogenesis of giant osteoclasts in Paget's disease of bone was studied by means of electron microscopy. 26 iliac crest biopsies were made and divided for light and electron microscopic investigation. A special procedure was used for electron microscopic preparation of bone without previous decalcification. Paget osteoclasts are characterized by their high content of nuclei. Several nuclei may show paracrystalline inclusions pointing to a possible virus infection of these cells. Giant osteoclasts have an increased mobility and a high resorptive activity, manifest by the dissection of bone fragments from endosteal bone surfaces. Cell membrane interdigitations between mononuclear cells and osteoclasts occur as a morphologic concomitant of cell fusion. Frequent occurence of such cell membrane contacts seem to indicate an increased tendency to cell fusion among the mononuclear precursors of Paget-osteoclasts. Precursor cells are located in the pericapillary region, and morphologically resemble pericytes. The assumption of an increased rate of cell fusion amoungst the precursor cells of osteoclasts might explain the development of giant osteoclasts in this disease. Further studies of the paracrystalline nuclear inclusions of Paget-osteoclasts are necessary to determine whether this process can be considered to be a cytopathogenic effect of virus infection.", "contents": "[Paget's disease of bone: ultrastructure and cytogenesis of osteoclasts (author's transl)]. The cytogenesis of giant osteoclasts in Paget's disease of bone was studied by means of electron microscopy. 26 iliac crest biopsies were made and divided for light and electron microscopic investigation. A special procedure was used for electron microscopic preparation of bone without previous decalcification. Paget osteoclasts are characterized by their high content of nuclei. Several nuclei may show paracrystalline inclusions pointing to a possible virus infection of these cells. Giant osteoclasts have an increased mobility and a high resorptive activity, manifest by the dissection of bone fragments from endosteal bone surfaces. Cell membrane interdigitations between mononuclear cells and osteoclasts occur as a morphologic concomitant of cell fusion. Frequent occurence of such cell membrane contacts seem to indicate an increased tendency to cell fusion among the mononuclear precursors of Paget-osteoclasts. Precursor cells are located in the pericapillary region, and morphologically resemble pericytes. The assumption of an increased rate of cell fusion amoungst the precursor cells of osteoclasts might explain the development of giant osteoclasts in this disease. Further studies of the paracrystalline nuclear inclusions of Paget-osteoclasts are necessary to determine whether this process can be considered to be a cytopathogenic effect of virus infection."}
{"id": "PMID:202071", "title": "Rod-shaped tubulated bodies in the endothelia of mesenteric arteries of hypertensive rats.", "content": "Weibel-Palade bodies were found in the endothelial cells of the mesenteric arteries of hypertensive rats. They were spherical or rod-shaped and bounded by a single membrane. They measured approximately 0.1 to 0.2 mu in diameter and up to 0.4 mu in length. The majority of them showed microtubular subunits, measuring about 200 A in width. These bodies are thought to originate from Golgi apparatus.", "contents": "Rod-shaped tubulated bodies in the endothelia of mesenteric arteries of hypertensive rats. Weibel-Palade bodies were found in the endothelial cells of the mesenteric arteries of hypertensive rats. They were spherical or rod-shaped and bounded by a single membrane. They measured approximately 0.1 to 0.2 mu in diameter and up to 0.4 mu in length. The majority of them showed microtubular subunits, measuring about 200 A in width. These bodies are thought to originate from Golgi apparatus."}
{"id": "PMID:202084", "title": "[Role of the oxidation-reduction state and phosphate potential in regulating rat liver gluconeogenesis during inclusion of 1,3-butanediol in the diet].", "content": "Gluconeogenesis was stimulated in rat liver tissues if 38.5% of carbohydrates were substituted in the diet by 1,3-butane diol used as a source of energy. Under these conditions concentration of substrates (phosphoenol pyruvate, malate, oxalacetate), participating in coupling of glycolysis and gluconeogenesis, was increased in liver tissue; activity of gluconeogenesis key enzymes (phosphoenolpyruvate carboxykinase and fructose-1,6-diphosphatase) was also increased. Decrease in the ratio NAD+/NADH showed that the nicotinamide nucleotide pool acquired the most distinct reducing properties of cytoplasma and mitochondria of rats maintained on the diet. The value of phosphate potential (the ration ATP/ADP/Pn) was decreased during the experiment due to increase of ATP utilization in gluconeogenesis.", "contents": "[Role of the oxidation-reduction state and phosphate potential in regulating rat liver gluconeogenesis during inclusion of 1,3-butanediol in the diet]. Gluconeogenesis was stimulated in rat liver tissues if 38.5% of carbohydrates were substituted in the diet by 1,3-butane diol used as a source of energy. Under these conditions concentration of substrates (phosphoenol pyruvate, malate, oxalacetate), participating in coupling of glycolysis and gluconeogenesis, was increased in liver tissue; activity of gluconeogenesis key enzymes (phosphoenolpyruvate carboxykinase and fructose-1,6-diphosphatase) was also increased. Decrease in the ratio NAD+/NADH showed that the nicotinamide nucleotide pool acquired the most distinct reducing properties of cytoplasma and mitochondria of rats maintained on the diet. The value of phosphate potential (the ration ATP/ADP/Pn) was decreased during the experiment due to increase of ATP utilization in gluconeogenesis."}
{"id": "PMID:202085", "title": "[Adenylate kinase and creatine kinase activity of rabbit blood serum following application of a tourniquet to the thigh].", "content": "A colorimetric method is described for estimation of the adenilate kinase activity in blood serum; the method is based on coupling of adenilate- and creatine kinase reactions and on estimation of the amount of creatine formed. Adenilate kinase activity in blood serum, estimated by the method, was shown to increase 4-fold after removing of tourniquet with subsequent normalization within the next day. The same data were obtained using a spectrophotometric method for estimation of adenilate kinase based on NADP reduction in coupled reactions with hexokinase and glucose-6-phosphate dehydrogenase. An increase in creatine kinase activity in blood serum occurred later on after removing of the tourniquet; it was more distinct (8.5-fold) and maintained longer as compared with the increase in adenilate kinase activity.", "contents": "[Adenylate kinase and creatine kinase activity of rabbit blood serum following application of a tourniquet to the thigh]. A colorimetric method is described for estimation of the adenilate kinase activity in blood serum; the method is based on coupling of adenilate- and creatine kinase reactions and on estimation of the amount of creatine formed. Adenilate kinase activity in blood serum, estimated by the method, was shown to increase 4-fold after removing of tourniquet with subsequent normalization within the next day. The same data were obtained using a spectrophotometric method for estimation of adenilate kinase based on NADP reduction in coupled reactions with hexokinase and glucose-6-phosphate dehydrogenase. An increase in creatine kinase activity in blood serum occurred later on after removing of the tourniquet; it was more distinct (8.5-fold) and maintained longer as compared with the increase in adenilate kinase activity."}
{"id": "PMID:202086", "title": "[Vessel wall lipids in human atherosclerosis].", "content": "Relative content of linoleic acid in the fraction of cholesterol esters was increased in \"unaltered\" intima of human aorta in course of aging. Due to this phenomenon the fatty acid composition of this lipid fraction became similar to the composition of cholesterol esters in lipoproteins of low density, observed in blood of persons at the age of 50 and older. Lipids were accumulated extracellularly in intima of aorta in the course of aging. The high ratio of linoleic acid was also typical for the fatty acid composition of cholesterol esters in fibrous patch with area of atheromatosis (amorphous accumulation of fat, localized out of the cells). These data demonstrate that lipoproteins of low density from blood serum may serve as a source of accumulation of lipids both in \"unaltered\" intima in the course of ageing and in fibrous patch. The lower ration of linoleic acid and relatively higher content of oleic acid were the characteristic properties of cholesterol esters from lipid spots (\"early impairment\") as compared with intima and atheroma. Cells of lipid spots, filled with fat, might apparently degrade the liproproteins from blood serum and the liberated cholesterol could be esterified by fatty acids, newly synthesized or preformed in the cells.", "contents": "[Vessel wall lipids in human atherosclerosis]. Relative content of linoleic acid in the fraction of cholesterol esters was increased in \"unaltered\" intima of human aorta in course of aging. Due to this phenomenon the fatty acid composition of this lipid fraction became similar to the composition of cholesterol esters in lipoproteins of low density, observed in blood of persons at the age of 50 and older. Lipids were accumulated extracellularly in intima of aorta in the course of aging. The high ratio of linoleic acid was also typical for the fatty acid composition of cholesterol esters in fibrous patch with area of atheromatosis (amorphous accumulation of fat, localized out of the cells). These data demonstrate that lipoproteins of low density from blood serum may serve as a source of accumulation of lipids both in \"unaltered\" intima in the course of ageing and in fibrous patch. The lower ration of linoleic acid and relatively higher content of oleic acid were the characteristic properties of cholesterol esters from lipid spots (\"early impairment\") as compared with intima and atheroma. Cells of lipid spots, filled with fat, might apparently degrade the liproproteins from blood serum and the liberated cholesterol could be esterified by fatty acids, newly synthesized or preformed in the cells."}
{"id": "PMID:202088", "title": "[Changes in skin enzyme activity in experimental burns].", "content": "Activities of proteolytic enzymes--cathepsins B and D, trypsin-like proteases, leucine aminopeptidase--as well as of lactate dehydrogenase and its isoenzymes were studied in area of thermic burns of skin and hypodermic tissue, in the zone surrounding the burns area and in intact skin of burned rats. Within a day after burns activities of the enzymes studied were distinctly decreased. The low levels of the activities were within the next three weeks. The activities of the proteolytic enzymes were gradually restored and exceeded the normal level in the tissues situated under crust, in boundary zone and in leukocytes of demarcational zone; the increase in activity appears to affect the subsequent deepening of burn wounds.", "contents": "[Changes in skin enzyme activity in experimental burns]. Activities of proteolytic enzymes--cathepsins B and D, trypsin-like proteases, leucine aminopeptidase--as well as of lactate dehydrogenase and its isoenzymes were studied in area of thermic burns of skin and hypodermic tissue, in the zone surrounding the burns area and in intact skin of burned rats. Within a day after burns activities of the enzymes studied were distinctly decreased. The low levels of the activities were within the next three weeks. The activities of the proteolytic enzymes were gradually restored and exceeded the normal level in the tissues situated under crust, in boundary zone and in leukocytes of demarcational zone; the increase in activity appears to affect the subsequent deepening of burn wounds."}
{"id": "PMID:202087", "title": "[Energy metabolism disorders in the myocardium due to alcoholic intoxication].", "content": "Energy metabolism was studied in rat myocardial mitochondria by estimation of respiratory enzymes activity and content of the Krebs cycle substrates under conditions of acute and chronic intoxication with ethyl alcohol. In the acute intoxication mitochondrial redox enzymes were inhibited (glutamate- and malate dehydrogenases, NADH cytochrome C oxidoreductase and cytochrome C oxidase), succinate- and lactate dehydrogenases were activated; at the same time, contents of pyruvate, succinate, and alpha-ketoglutarate were elevated and the content of oxalacetic acid was decreased. Prolonged administration of alcohol (within 2 months) caused an intensification of glycolysis and an increase in NADH cytochrome C oxidoreductase pathway with preferable oxidation of succinate and activation of cytochrome C oxidase; the phenomenon appears to be an adaptation to chronic \"alcohol hypoxia\". Discontinuation of alcohol administration led to deficiency of native substrates in myocardium (primarily, oxalacetic and succinic acids) due to decrease in NAD reduction via alcohol dehydrogenase reaction and to increase in oxidation of NAD-dependent endogenous substrates.", "contents": "[Energy metabolism disorders in the myocardium due to alcoholic intoxication]. Energy metabolism was studied in rat myocardial mitochondria by estimation of respiratory enzymes activity and content of the Krebs cycle substrates under conditions of acute and chronic intoxication with ethyl alcohol. In the acute intoxication mitochondrial redox enzymes were inhibited (glutamate- and malate dehydrogenases, NADH cytochrome C oxidoreductase and cytochrome C oxidase), succinate- and lactate dehydrogenases were activated; at the same time, contents of pyruvate, succinate, and alpha-ketoglutarate were elevated and the content of oxalacetic acid was decreased. Prolonged administration of alcohol (within 2 months) caused an intensification of glycolysis and an increase in NADH cytochrome C oxidoreductase pathway with preferable oxidation of succinate and activation of cytochrome C oxidase; the phenomenon appears to be an adaptation to chronic \"alcohol hypoxia\". Discontinuation of alcohol administration led to deficiency of native substrates in myocardium (primarily, oxalacetic and succinic acids) due to decrease in NAD reduction via alcohol dehydrogenase reaction and to increase in oxidation of NAD-dependent endogenous substrates."}
{"id": "PMID:202089", "title": "[Phospholipid composition of high density lipoproteins in hyperalphalipoproteinemia].", "content": "Content of lecithin as related to the total content of phospholipids was increased in alpha-lipoproteins of healthy men with hyper-alpha-lipoproteinemia (concentration of cholesterol exceeded 72 mg% in the lipoproteins). The alpha-lipoproteins accumulated considerably more free cholesterol than its esters; this caused a decrease in the molar ration \"phospholipids/free cholesterol\". The surface of phospholipid-cholesterol monolayer of alpha-lipoproteins is apparently responsible for retaining of increased amounts of cholesterol in the complex as well as for participation of these structures in enzymatic reactions in blood serum.", "contents": "[Phospholipid composition of high density lipoproteins in hyperalphalipoproteinemia]. Content of lecithin as related to the total content of phospholipids was increased in alpha-lipoproteins of healthy men with hyper-alpha-lipoproteinemia (concentration of cholesterol exceeded 72 mg% in the lipoproteins). The alpha-lipoproteins accumulated considerably more free cholesterol than its esters; this caused a decrease in the molar ration \"phospholipids/free cholesterol\". The surface of phospholipid-cholesterol monolayer of alpha-lipoproteins is apparently responsible for retaining of increased amounts of cholesterol in the complex as well as for participation of these structures in enzymatic reactions in blood serum."}
{"id": "PMID:202095", "title": "[Serum factors that inhibit in vitro immunological reactions in malignant tumor development in experimental animals].", "content": "In two immunological reactions (immunocytoadherence and inhibition of macrophage adherence in the presence of specific antigens) it was shown that autologous and homologous native sera in some percentage of cases render an inhibitory effect. One of the blocking factors of sera proved to be rather thermostable, the other, on the contrary, to be thermolable.", "contents": "[Serum factors that inhibit in vitro immunological reactions in malignant tumor development in experimental animals]. In two immunological reactions (immunocytoadherence and inhibition of macrophage adherence in the presence of specific antigens) it was shown that autologous and homologous native sera in some percentage of cases render an inhibitory effect. One of the blocking factors of sera proved to be rather thermostable, the other, on the contrary, to be thermolable."}
{"id": "PMID:202091", "title": "[Cyclic adenosine monophosphate and atherogenic factors].", "content": "Hypercholesterolemia caused a decrease in the activity of adenylcyclase in rabbit liver tissue and in thrombocytes; hypertriglyceridemia, which developed after administration of hydrocortisone, led to an increase in the activity of adenylcyclase and in the content of 3,5-AMP in adipose tissue. Activities of adenylcyclase, phosphodiesterase and content of prostaglandines E1 and F2alpha were measured in thrombocytes of 39 healthy men without any symptoms of of ischemic heart impairment, in 52 patients with coronary atherosclerosis of the III degree (by Myasnikov's classification) as well as in 12 patients during the period of rehabilitation after myocardial infarction. The activity of adenylate cyclase system was impaired in atherosclerosis. This phenomenon might be caused by alteration in concentration of glucocorticoids in the organism.", "contents": "[Cyclic adenosine monophosphate and atherogenic factors]. Hypercholesterolemia caused a decrease in the activity of adenylcyclase in rabbit liver tissue and in thrombocytes; hypertriglyceridemia, which developed after administration of hydrocortisone, led to an increase in the activity of adenylcyclase and in the content of 3,5-AMP in adipose tissue. Activities of adenylcyclase, phosphodiesterase and content of prostaglandines E1 and F2alpha were measured in thrombocytes of 39 healthy men without any symptoms of of ischemic heart impairment, in 52 patients with coronary atherosclerosis of the III degree (by Myasnikov's classification) as well as in 12 patients during the period of rehabilitation after myocardial infarction. The activity of adenylate cyclase system was impaired in atherosclerosis. This phenomenon might be caused by alteration in concentration of glucocorticoids in the organism."}
{"id": "PMID:202090", "title": "[Effect of cortisol on adenylate cyclase and 3',5'-AMP phosphodiesterase activity and 3',5'-AMP concentration in tissues and biological fluids in experimental atherosclerosis].", "content": "Administration of hydrocortisone into healthy rabbits activated adenilate cyclase and phosphodiesterase in liver tissue; activity of the enzymes was normalized within 5 days after the treatment. The hormone, administered into animals with experimental cholesterol-induced atherosclerosis, caused an activation of adenilate cyclase and inhibition of phosphodiesterase; due to the phenomenon more distinct and long-term increase in cAMP concentration was observed in kidney, liver and fatty tissues. Concentration of cAMP exceeded considerably its initial content in the tissues within 5 days after the hydrocortisone administration. Hydrocortisone inhibited the adenilate cyclase system activity in adrenal cortex of experimental and control animals at early period of the experiment. In health rabbits content of cAMP was increased in adrenal cortex within 5 days after the hormone administration. As the similar effect was not found in animals with experimental atherosclerosis these data suggest that the hypophysis-adrenal cortex system under the experimental conditions studied was inhibited.", "contents": "[Effect of cortisol on adenylate cyclase and 3',5'-AMP phosphodiesterase activity and 3',5'-AMP concentration in tissues and biological fluids in experimental atherosclerosis]. Administration of hydrocortisone into healthy rabbits activated adenilate cyclase and phosphodiesterase in liver tissue; activity of the enzymes was normalized within 5 days after the treatment. The hormone, administered into animals with experimental cholesterol-induced atherosclerosis, caused an activation of adenilate cyclase and inhibition of phosphodiesterase; due to the phenomenon more distinct and long-term increase in cAMP concentration was observed in kidney, liver and fatty tissues. Concentration of cAMP exceeded considerably its initial content in the tissues within 5 days after the hydrocortisone administration. Hydrocortisone inhibited the adenilate cyclase system activity in adrenal cortex of experimental and control animals at early period of the experiment. In health rabbits content of cAMP was increased in adrenal cortex within 5 days after the hormone administration. As the similar effect was not found in animals with experimental atherosclerosis these data suggest that the hypophysis-adrenal cortex system under the experimental conditions studied was inhibited."}
{"id": "PMID:202092", "title": "[Cholesterol metabolism in rabbits with resistance to experimental atherosclerosis acquired by immunological treatment].", "content": "Development of resistance to experimental atherosclerosis due to immunization of newborn rabbits with homologous fraction of beta- and pre-beta-lipoproteins was accompanied by increased oxidation of cholesterol to biliary acids and by accelerated excretion of cholesterol. The phenomenon appears to be caused by two mechanisms: 1 (cholesterol, occurring in the fraction of free lipoproteins \"unblocked\" by the antibody (immunzied animals), is more readily oxidized to biliary acids in liver tissue than cholesterol, occurring in the autoimmune complex \"lipoprotein-antibody\" (non-immunized animals)); 2) the enzymes and biological systems, responsible for elimination of cholesterol from an organism (oxidation to biliary acids, excretion with bile), are activated after immunization of the newborn animals by the lipoprotein fraction endriched with cholesterol.", "contents": "[Cholesterol metabolism in rabbits with resistance to experimental atherosclerosis acquired by immunological treatment]. Development of resistance to experimental atherosclerosis due to immunization of newborn rabbits with homologous fraction of beta- and pre-beta-lipoproteins was accompanied by increased oxidation of cholesterol to biliary acids and by accelerated excretion of cholesterol. The phenomenon appears to be caused by two mechanisms: 1 (cholesterol, occurring in the fraction of free lipoproteins \"unblocked\" by the antibody (immunzied animals), is more readily oxidized to biliary acids in liver tissue than cholesterol, occurring in the autoimmune complex \"lipoprotein-antibody\" (non-immunized animals)); 2) the enzymes and biological systems, responsible for elimination of cholesterol from an organism (oxidation to biliary acids, excretion with bile), are activated after immunization of the newborn animals by the lipoprotein fraction endriched with cholesterol."}
{"id": "PMID:202099", "title": "[Use of EDP (electronic data processing) in the after care for heart-infarct patients].", "content": "It is demonstrated an after-treatment model for patients with myocardial infarction as a part of a complex project of electronic data processing within prevention and treatment of selected diseases of the heart and circulatory system (electronic data processing project myocardial infarction). The aim of the after-treatment project is the establishment and ambulatory medical after-treatment of all patients with myocardial infarction of a territory, by means of which without any additional manual expenditure by giving standardized evidences of data and using electronic data processing automatic letters of doctors and working lists may be established and scientific evaluations may be made possible.", "contents": "[Use of EDP (electronic data processing) in the after care for heart-infarct patients]. It is demonstrated an after-treatment model for patients with myocardial infarction as a part of a complex project of electronic data processing within prevention and treatment of selected diseases of the heart and circulatory system (electronic data processing project myocardial infarction). The aim of the after-treatment project is the establishment and ambulatory medical after-treatment of all patients with myocardial infarction of a territory, by means of which without any additional manual expenditure by giving standardized evidences of data and using electronic data processing automatic letters of doctors and working lists may be established and scientific evaluations may be made possible."}
{"id": "PMID:202094", "title": "[Pyridoxal kinase activity in human tumor tissues].", "content": "Activity of pyridoxal kinase (per 1 g of tissue or per 1 mg of protein) varied in the range from 7 to 39 un or from 0.079 to 0.4 un in human malignant neoplasm tissues (adenocarcinoma of various localization, squamatous cell carcinoma of lungs, skin melanoma). The direction of alterations in the pyridoxal kinase activity differed in various tumors studied as compared with the respective controls (unimpaired tissues used for growing malignant cells).", "contents": "[Pyridoxal kinase activity in human tumor tissues]. Activity of pyridoxal kinase (per 1 g of tissue or per 1 mg of protein) varied in the range from 7 to 39 un or from 0.079 to 0.4 un in human malignant neoplasm tissues (adenocarcinoma of various localization, squamatous cell carcinoma of lungs, skin melanoma). The direction of alterations in the pyridoxal kinase activity differed in various tumors studied as compared with the respective controls (unimpaired tissues used for growing malignant cells)."}
{"id": "PMID:202093", "title": "[Bone tissue collagen and vitamin D in chronic kidney insufficiency in rats].", "content": "Chronic kidney insufficiency, caused by subtotal nephrectomy, did not lead to distinct alterations in hydroxyproline concentration in blood and to its excretion in rats within 1-1.5 months after the operation. Content of salt-soluble collagen was decreased in diaphyses of rat tubular bones in chronic kidney insufficiency; in the epiphyses (with metaphyses) content of the collagen fraction was increased, but the concentration of non-soluble collagen was unaltered. Decrease in content of salt-soluble collagen in diaphyses in chronic kidney insufficiency was similar to that in experimental vitamin D deficiency. The decrease might be due to impairment in formation of the active form of vitamin D-1,25-dihydroxycholecalciferol. Other pathogenetic factors (effect of uremic toxins and stress) were apparently of primary importance for development of impairments of collagen metabolism in epiphyses. Dihydrotachysterol, the structural analogue of 1,25-dihydroxycholecalciferol, normalized the alterations in content of salt-soluble collagen in diaphyses and did not affect the impairments of collagen metabolism in epiphyses of rat bones in chronic kidney insufficiency.", "contents": "[Bone tissue collagen and vitamin D in chronic kidney insufficiency in rats]. Chronic kidney insufficiency, caused by subtotal nephrectomy, did not lead to distinct alterations in hydroxyproline concentration in blood and to its excretion in rats within 1-1.5 months after the operation. Content of salt-soluble collagen was decreased in diaphyses of rat tubular bones in chronic kidney insufficiency; in the epiphyses (with metaphyses) content of the collagen fraction was increased, but the concentration of non-soluble collagen was unaltered. Decrease in content of salt-soluble collagen in diaphyses in chronic kidney insufficiency was similar to that in experimental vitamin D deficiency. The decrease might be due to impairment in formation of the active form of vitamin D-1,25-dihydroxycholecalciferol. Other pathogenetic factors (effect of uremic toxins and stress) were apparently of primary importance for development of impairments of collagen metabolism in epiphyses. Dihydrotachysterol, the structural analogue of 1,25-dihydroxycholecalciferol, normalized the alterations in content of salt-soluble collagen in diaphyses and did not affect the impairments of collagen metabolism in epiphyses of rat bones in chronic kidney insufficiency."}
{"id": "PMID:202101", "title": "Induction of liver tumors in rats by sodium nitrite and methylguanidine.", "content": "The carcinogenicity of sodium nitrite and methylguanidine singly and together were examined in rats. A hepatocellular carcinoma, a hemangiosarcoma and a spindle cell sarcoma  were found in 3 of 15 rats fed continuously on pellet diet containing 0.16% sodium nitrite and 0.16% methylguanidine. Hemangiomas and bile duct adenomas of the liver were also found in 6 and 8, respectively, of the 15 rats in this group. Hemangiomas and bile ducts adenomas of the liver were found in 2 and 3, respectively, of the 4 rats fed on pellet diet containing 0.16% sodium nitrite. Only 1 of 5 rats fed on pellet diet containing 0.16% methylguanidine developed a hemangioma. No tumor was found in the control group. All the tumors were found in rats that survived for over 12 months. No significant changes were detected in the esophagus or stomach.", "contents": "Induction of liver tumors in rats by sodium nitrite and methylguanidine. The carcinogenicity of sodium nitrite and methylguanidine singly and together were examined in rats. A hepatocellular carcinoma, a hemangiosarcoma and a spindle cell sarcoma  were found in 3 of 15 rats fed continuously on pellet diet containing 0.16% sodium nitrite and 0.16% methylguanidine. Hemangiomas and bile duct adenomas of the liver were also found in 6 and 8, respectively, of the 15 rats in this group. Hemangiomas and bile ducts adenomas of the liver were found in 2 and 3, respectively, of the 4 rats fed on pellet diet containing 0.16% sodium nitrite. Only 1 of 5 rats fed on pellet diet containing 0.16% methylguanidine developed a hemangioma. No tumor was found in the control group. All the tumors were found in rats that survived for over 12 months. No significant changes were detected in the esophagus or stomach."}
{"id": "PMID:202102", "title": "Chemotherapy studies in autochthonous rat tumors: hepatomas.", "content": "Diethylnitrosamine (DEN) was applied orally to a total of 250 female Wistar rats in a single dose (d) of 3 mg/kg body weight 5 times a week for a duration of 20 weeks. After approximately 150 days exploratory laparotomy was performed to all animals. By inspection of the liver they were divided into 4 stages of disease according to the extent of cancer formation. The reaction of rats with DEN induced liver tumors was tested using a 4-drug combination chemotherapy with different equitoxic doses of Adriamycin (Adm), Methotrexate (Mtx), 5-Fluorouracil (5-FU) and Cyclophosphamide (CP). No benefit of drug treatment could be noted. In drug treated animals no decrease in the development of the liver tumors, in the frequency of metastases nor in the frequency of tumors of other origin could be demonstrated. The parallels of chemotherapy in chemically induced liver cancer to clinical experience are discussed.", "contents": "Chemotherapy studies in autochthonous rat tumors: hepatomas. Diethylnitrosamine (DEN) was applied orally to a total of 250 female Wistar rats in a single dose (d) of 3 mg/kg body weight 5 times a week for a duration of 20 weeks. After approximately 150 days exploratory laparotomy was performed to all animals. By inspection of the liver they were divided into 4 stages of disease according to the extent of cancer formation. The reaction of rats with DEN induced liver tumors was tested using a 4-drug combination chemotherapy with different equitoxic doses of Adriamycin (Adm), Methotrexate (Mtx), 5-Fluorouracil (5-FU) and Cyclophosphamide (CP). No benefit of drug treatment could be noted. In drug treated animals no decrease in the development of the liver tumors, in the frequency of metastases nor in the frequency of tumors of other origin could be demonstrated. The parallels of chemotherapy in chemically induced liver cancer to clinical experience are discussed."}
{"id": "PMID:202105", "title": "[Comparative study of the morphofunctional organization of tissues of different regions of the rat brain in culture].", "content": "The morphological organization and spontaneous electrical activity of neurones of the hippocampus, visual cortex and cerebellum of one- two-day old rats were studied during prolonged cultivation (up to 35 days) of explants under indentical conditions in vitro. Differentiation of cells, myelinization of axons and formation of synapses between the neurones were observed. A continuous and periodic types of unit activity were recorded which, for the hippocampus did not depend on the time of cultivation and units' location in the explant. The cerebral cortex cultures displayed a transition of continuous unit activity to a periodic one after a two-week development of the explants in vitro. The process coincides with the increase in the number of synapses in the culture and their structural maturation. The periodic discharges observed in mature cultures of the cerebral cortex and in the central part of the cerebellum explants, are transformed into continuous ones under the action ofmagnesium ions.", "contents": "[Comparative study of the morphofunctional organization of tissues of different regions of the rat brain in culture]. The morphological organization and spontaneous electrical activity of neurones of the hippocampus, visual cortex and cerebellum of one- two-day old rats were studied during prolonged cultivation (up to 35 days) of explants under indentical conditions in vitro. Differentiation of cells, myelinization of axons and formation of synapses between the neurones were observed. A continuous and periodic types of unit activity were recorded which, for the hippocampus did not depend on the time of cultivation and units' location in the explant. The cerebral cortex cultures displayed a transition of continuous unit activity to a periodic one after a two-week development of the explants in vitro. The process coincides with the increase in the number of synapses in the culture and their structural maturation. The periodic discharges observed in mature cultures of the cerebral cortex and in the central part of the cerebellum explants, are transformed into continuous ones under the action ofmagnesium ions."}
{"id": "PMID:202111", "title": "A mixed outbreak of epidemic keratoconjunctivitis due to adenoviruses types 29 and 8.", "content": "An outbreak of epidemic keratoconjunctivitis (EKC) occurred in northern Bohemia in the summer of 1975. One hundred and four patients were treated. Four strains of adenovirus type 29 with low or strong pronounced cross-neutralization against anti-Ad 15 reference serum, and 2 adenovirus type 8 were isolated of 4 patients. Type 8 strains were only obtained from conjunctiva, type 29 also from stools. From one patient, type 8 from conjunctiva and type 29 from stool were isolated simultaneously. Out of 22 patients with demonstrable antibody rise, a monotypic response in virus-neutralization test against type 29 was detected in 13 and a mixed response against types 29 and 8 in nine. An antibody rise was most frequently demonstrated by virus-neutralization test, the frequence for VNT alone being equal to the frequency of antibody rise as detected by VNT, hemagglutination-inhibition test and complement-fixation test in combination.", "contents": "A mixed outbreak of epidemic keratoconjunctivitis due to adenoviruses types 29 and 8. An outbreak of epidemic keratoconjunctivitis (EKC) occurred in northern Bohemia in the summer of 1975. One hundred and four patients were treated. Four strains of adenovirus type 29 with low or strong pronounced cross-neutralization against anti-Ad 15 reference serum, and 2 adenovirus type 8 were isolated of 4 patients. Type 8 strains were only obtained from conjunctiva, type 29 also from stools. From one patient, type 8 from conjunctiva and type 29 from stool were isolated simultaneously. Out of 22 patients with demonstrable antibody rise, a monotypic response in virus-neutralization test against type 29 was detected in 13 and a mixed response against types 29 and 8 in nine. An antibody rise was most frequently demonstrated by virus-neutralization test, the frequence for VNT alone being equal to the frequency of antibody rise as detected by VNT, hemagglutination-inhibition test and complement-fixation test in combination."}
{"id": "PMID:202107", "title": "[Development of action potentials spreading antidromally from an acute epileptogenic focus through the corpus callosum].", "content": "The activity of callosal neurones located in the sensorimotor cortical area was studied in unanaesthetized rabbits. An epileptogenic focus was produced by application of penicillin or strychnine in the homotopic region of the contralateral hemisphere. During hyperpolarization of the membrane, corresponding to the appearance of paraxysmal discharges in the homotopic area, some of the neurones exhibited a group of antidromic action potentials (APs) in their soma with a 70-80 msec latency. Analysis of the APs form and of interspike intervals between the tested APs and antidromic APs evoked by stimulation, allowed to identify spontaneous antidromic APs in the extracellular records of callosal neurones as well. The data obtained show that under the influence of epileptogenic agents in the axon terminals located in the focus of the epileptic activity APs may appear, spreading antidromally through the corpus callosum to the soma of the callosal neurones.", "contents": "[Development of action potentials spreading antidromally from an acute epileptogenic focus through the corpus callosum]. The activity of callosal neurones located in the sensorimotor cortical area was studied in unanaesthetized rabbits. An epileptogenic focus was produced by application of penicillin or strychnine in the homotopic region of the contralateral hemisphere. During hyperpolarization of the membrane, corresponding to the appearance of paraxysmal discharges in the homotopic area, some of the neurones exhibited a group of antidromic action potentials (APs) in their soma with a 70-80 msec latency. Analysis of the APs form and of interspike intervals between the tested APs and antidromic APs evoked by stimulation, allowed to identify spontaneous antidromic APs in the extracellular records of callosal neurones as well. The data obtained show that under the influence of epileptogenic agents in the axon terminals located in the focus of the epileptic activity APs may appear, spreading antidromally through the corpus callosum to the soma of the callosal neurones."}
{"id": "PMID:202112", "title": "[Lipoproteins as serum inhibitors in rubella hemagglutination inhibition test and their elimination (author's transl)].", "content": "Lipoproteins of 20 human sera were isolated by flotation centrifugation and tested for inhibitory activity in rubella HI-test. Low density lipoproteins (LDL) showed the highest titers with an average of 1:238,0, whereas the others (VLDL, HDL) had lower titers (see tab. 2). The greatest reduction of all classes of lipoproteins was achieved with kaolin treatment. Heparin-manganous chloride and dextran sulfate-calcium chloride method mainly reduced the LDL (84.4 resp. 78.7%). In a comparative test sera treated with the heparin procedure showed higher antibody titers than those treated with dextran sulfate.", "contents": "[Lipoproteins as serum inhibitors in rubella hemagglutination inhibition test and their elimination (author's transl)]. Lipoproteins of 20 human sera were isolated by flotation centrifugation and tested for inhibitory activity in rubella HI-test. Low density lipoproteins (LDL) showed the highest titers with an average of 1:238,0, whereas the others (VLDL, HDL) had lower titers (see tab. 2). The greatest reduction of all classes of lipoproteins was achieved with kaolin treatment. Heparin-manganous chloride and dextran sulfate-calcium chloride method mainly reduced the LDL (84.4 resp. 78.7%). In a comparative test sera treated with the heparin procedure showed higher antibody titers than those treated with dextran sulfate."}
{"id": "PMID:202109", "title": "Detection of collagenase-activity in RA synovial fluids using soluble 14C-labelled collagen.", "content": "14 RA synovial fluids and 7 non-RA synovial fluids were investigated as to their collagenase-activity using 14C-labelled type I human collagen in soluble form. Breakdown products were fractionated by gel filtration on Sephadex G 200 superfine. Cleavage of native and denatured labelled collagen was compared. 11 RA synovial fluids showed significant collagenase activity as manifested by degradation of native collagen, while only one synovial fluid of the control group displayed a significant collagenolytic activity. Results were compared with cleavage of reconstituted collagen fibrils. Influence of EDTA and KSCN on collagen degradation was also studied: EDTA completely blocked degradation of native or denatured collagen, while KSCN caused an increase of collagenolytic activity in two cases.", "contents": "Detection of collagenase-activity in RA synovial fluids using soluble 14C-labelled collagen. 14 RA synovial fluids and 7 non-RA synovial fluids were investigated as to their collagenase-activity using 14C-labelled type I human collagen in soluble form. Breakdown products were fractionated by gel filtration on Sephadex G 200 superfine. Cleavage of native and denatured labelled collagen was compared. 11 RA synovial fluids showed significant collagenase activity as manifested by degradation of native collagen, while only one synovial fluid of the control group displayed a significant collagenolytic activity. Results were compared with cleavage of reconstituted collagen fibrils. Influence of EDTA and KSCN on collagen degradation was also studied: EDTA completely blocked degradation of native or denatured collagen, while KSCN caused an increase of collagenolytic activity in two cases."}
{"id": "PMID:202117", "title": "[Immunogenicity and toxicity of soluble trichloroacetic acid precipitate from pertussis microbes and its fractions].", "content": "The authors studied the biological properties of the preparations of pertussis protective antigens obtained by the disintegration of the microbial mass of Bordetella pertussis, with the subsequent purification with trichloracetic acid (TCA-preparations). TCA-preparations proved to possess a stable protective activity and by the ratio of the protective dose to toxic and histamine-sensitizing doses considerably exceeded the corpuscular vaccine. A TCA-preparation fraction with a greater immunogenic activity than the initial preparation was obtained by chromatography on sepharose 4B.", "contents": "[Immunogenicity and toxicity of soluble trichloroacetic acid precipitate from pertussis microbes and its fractions]. The authors studied the biological properties of the preparations of pertussis protective antigens obtained by the disintegration of the microbial mass of Bordetella pertussis, with the subsequent purification with trichloracetic acid (TCA-preparations). TCA-preparations proved to possess a stable protective activity and by the ratio of the protective dose to toxic and histamine-sensitizing doses considerably exceeded the corpuscular vaccine. A TCA-preparation fraction with a greater immunogenic activity than the initial preparation was obtained by chromatography on sepharose 4B."}
{"id": "PMID:202120", "title": "[Changes in the nervous system in kidney diseases].", "content": "A total of 150 patients with renal pathology (chronic glomerulonephritis, pyelonephritis, urolithiasis, etc.) accompanied by the development of psychoneurological disturbances were examined. In the initial stage of the renal insufficiency the authors observed neurasthenic, radicular, polyneuritic, renovisceral syndromes, in a more remote stage--encephalopathies and disturbances of the brain circulation. The important part in the above-mentioned disturbances is played by azotemia, metabolic acidosis, disturbances of fluid-electrolyte and albumine balance, as well as arterial hypertension.", "contents": "[Changes in the nervous system in kidney diseases]. A total of 150 patients with renal pathology (chronic glomerulonephritis, pyelonephritis, urolithiasis, etc.) accompanied by the development of psychoneurological disturbances were examined. In the initial stage of the renal insufficiency the authors observed neurasthenic, radicular, polyneuritic, renovisceral syndromes, in a more remote stage--encephalopathies and disturbances of the brain circulation. The important part in the above-mentioned disturbances is played by azotemia, metabolic acidosis, disturbances of fluid-electrolyte and albumine balance, as well as arterial hypertension."}
{"id": "PMID:202121", "title": "Histochemical studies on reserve substances and enzymes in female gametophyte of Zea mays.", "content": "Cytochemical changes during the early development of maize caryopsis are reported. Changes in the localization of different reserve substances (e.g. polysaccharides, proteins, nucleic acids and lipids) and enzymes (acid phosphatase, esterase, lipase, phosphorylase, succinate dehydrogenase, cytochrome oxidase and peroxidase) have been studied in unfertilized and fertilized ovules. Before pollination very feeble enzyme activity (acid phosphatase, succinate dehydrogenase, cytochrome oxidase and peroxidase) was observed. Reserve substances were present in low amounts before pollination. Pollination stimulated the accumulation of several substances and enzymes in the tip of the nucellus, micropylar zone. Just prior to, during and after fertilization, the cells in the micropylar zone had strong reaction for several enzymes indicating temporary enhancement of metabolic activity in the micropylar zone. The role of antipodals in the storage of reserve food products and nutrition of embryo and early stages of endosperm development is discussed. The pattern of enzymatic changes within the embryo sac reflected the biochemical changes operative during quiescent and active stages. The nucellus of Zea mays contains many enzymes required for hydrolysis of reserved food substances. A role of acid phosphatase in autolysis of nucellar cells, after fertilization is suggested. Post-fertilization increase in the activity of enzymes and accumulation of reserve materials is interpreted as reflecting a presumed increase in the metabolic rate relative to growth and differentiation.", "contents": "Histochemical studies on reserve substances and enzymes in female gametophyte of Zea mays. Cytochemical changes during the early development of maize caryopsis are reported. Changes in the localization of different reserve substances (e.g. polysaccharides, proteins, nucleic acids and lipids) and enzymes (acid phosphatase, esterase, lipase, phosphorylase, succinate dehydrogenase, cytochrome oxidase and peroxidase) have been studied in unfertilized and fertilized ovules. Before pollination very feeble enzyme activity (acid phosphatase, succinate dehydrogenase, cytochrome oxidase and peroxidase) was observed. Reserve substances were present in low amounts before pollination. Pollination stimulated the accumulation of several substances and enzymes in the tip of the nucellus, micropylar zone. Just prior to, during and after fertilization, the cells in the micropylar zone had strong reaction for several enzymes indicating temporary enhancement of metabolic activity in the micropylar zone. The role of antipodals in the storage of reserve food products and nutrition of embryo and early stages of endosperm development is discussed. The pattern of enzymatic changes within the embryo sac reflected the biochemical changes operative during quiescent and active stages. The nucellus of Zea mays contains many enzymes required for hydrolysis of reserved food substances. A role of acid phosphatase in autolysis of nucellar cells, after fertilization is suggested. Post-fertilization increase in the activity of enzymes and accumulation of reserve materials is interpreted as reflecting a presumed increase in the metabolic rate relative to growth and differentiation."}
{"id": "PMID:202122", "title": "Phosphatases in the accessory respiratory organs of two fresh-water fishes.", "content": "The distribution of enzymes, viz., alkaline phosphatase, acid phosphatase, adenosine monophosphatase and adenosine triphosphatase was studied by histochemical methods in the accessory respiratory organs of two fresh-water fishes (Clarius batrachus and Heteropneustes fossilis). Enzymes have been used as markers to differentiate between functional and non-functional cells of the dendritic organ of Clarius and of the air chamber of Heteropneustes. The variations in the enzyme activities have been correlated with the functional capacity of each respiratory organ. It is attempted to understand the physiological role of these enzymes in the process of aerial breathing.", "contents": "Phosphatases in the accessory respiratory organs of two fresh-water fishes. The distribution of enzymes, viz., alkaline phosphatase, acid phosphatase, adenosine monophosphatase and adenosine triphosphatase was studied by histochemical methods in the accessory respiratory organs of two fresh-water fishes (Clarius batrachus and Heteropneustes fossilis). Enzymes have been used as markers to differentiate between functional and non-functional cells of the dendritic organ of Clarius and of the air chamber of Heteropneustes. The variations in the enzyme activities have been correlated with the functional capacity of each respiratory organ. It is attempted to understand the physiological role of these enzymes in the process of aerial breathing."}
{"id": "PMID:202123", "title": "Low-density lipoprotein complexes with histones.", "content": "Low-density lopoproteins (LDL) form soluble and insoluble complexes with the total histone and its fractions. The bulk of these complexes is formed by the arginine-rich histone fraction. LDL are bound with histones by means of ion binding.", "contents": "Low-density lipoprotein complexes with histones. Low-density lopoproteins (LDL) form soluble and insoluble complexes with the total histone and its fractions. The bulk of these complexes is formed by the arginine-rich histone fraction. LDL are bound with histones by means of ion binding."}
{"id": "PMID:202125", "title": "Studies on NAD+ permeability in intact mitochondria from rabbit reticulocytes.", "content": "Functionally intact mitochondria from rabbit reticulocytes are characterized by a low NAD+ level after the preparation (0.29 nmoles NAD+ + NADH/mg protein). They are apparently impermeable for NADH and exhibit a slow net uptake of NAD+. From the increase of O2-uptake in state 3 and the increase of NADH concentration in state 4 of respiration after the addition of NAD+ we concluded that 3--10 min are necessary for the saturation with NAD+ at 23 degrees C. 2mM NAD+ extramitochondrially are not sufficient to saturate the mitochondria with NADH and probably NAD+, too. Because of the net uptake of NAD+ we assume that reticulocyte mitochondria lose NAD+ during their preparation. If they are incubated with the physiological concentration of 300 micrometer NAD+, which was found in reticulocytes, a value of 1.9 nmoles NAD+ + NADH mg protein was calculated. At an extramitochondrial NAD+ concentration of 300 micrometer, reticulocyte mitochondria exhibit an almost maximal O2-uptake in the presence of oxaloacetate or alpha-ketoglutarate. It is concluded that the mitochondria in intact reticulocytes contain the \"normal\" complement of NAD+ + NADH.", "contents": "Studies on NAD+ permeability in intact mitochondria from rabbit reticulocytes. Functionally intact mitochondria from rabbit reticulocytes are characterized by a low NAD+ level after the preparation (0.29 nmoles NAD+ + NADH/mg protein). They are apparently impermeable for NADH and exhibit a slow net uptake of NAD+. From the increase of O2-uptake in state 3 and the increase of NADH concentration in state 4 of respiration after the addition of NAD+ we concluded that 3--10 min are necessary for the saturation with NAD+ at 23 degrees C. 2mM NAD+ extramitochondrially are not sufficient to saturate the mitochondria with NADH and probably NAD+, too. Because of the net uptake of NAD+ we assume that reticulocyte mitochondria lose NAD+ during their preparation. If they are incubated with the physiological concentration of 300 micrometer NAD+, which was found in reticulocytes, a value of 1.9 nmoles NAD+ + NADH mg protein was calculated. At an extramitochondrial NAD+ concentration of 300 micrometer, reticulocyte mitochondria exhibit an almost maximal O2-uptake in the presence of oxaloacetate or alpha-ketoglutarate. It is concluded that the mitochondria in intact reticulocytes contain the \"normal\" complement of NAD+ + NADH."}
{"id": "PMID:202126", "title": "Degradation of mitochondria by cytosolic factors in reticulocytes.", "content": "The degradation process of mitochondria in rabbit reticulocytes proceeds predominately directly in the cytosol rather than in secondary lysosomes as judged by electronmicroscopy. At least five cytosolic protein factors are present in reticulocytes, which could be related to the degradation of mitochondria: the two inhibitory proteins of the respiratory chain RF and RC and three enzymes which cause a lysis of mitochondria in vitro (lipoxygenase, proteinase, phospholipase A). The properties of these factors are the subject of this paper. A hypothetic scheme of the degradation of mitochondria in reticulocytes is proposed. The degradation of mitochondria in reticulocytes is viewed as a complex interplay of various cytosolic factors and the functional state of the mitochondrial membranes. The lipoxygenase damages the membranes and triggers the penetration of the respiratory inhibitors. In this manner, a catastrophic cycle is initiated which leads to the complete breakdown of the mitochondria.", "contents": "Degradation of mitochondria by cytosolic factors in reticulocytes. The degradation process of mitochondria in rabbit reticulocytes proceeds predominately directly in the cytosol rather than in secondary lysosomes as judged by electronmicroscopy. At least five cytosolic protein factors are present in reticulocytes, which could be related to the degradation of mitochondria: the two inhibitory proteins of the respiratory chain RF and RC and three enzymes which cause a lysis of mitochondria in vitro (lipoxygenase, proteinase, phospholipase A). The properties of these factors are the subject of this paper. A hypothetic scheme of the degradation of mitochondria in reticulocytes is proposed. The degradation of mitochondria in reticulocytes is viewed as a complex interplay of various cytosolic factors and the functional state of the mitochondrial membranes. The lipoxygenase damages the membranes and triggers the penetration of the respiratory inhibitors. In this manner, a catastrophic cycle is initiated which leads to the complete breakdown of the mitochondria."}
{"id": "PMID:202128", "title": "Grouping of patients with hyperparathyroidism by clinical signs, correlated to some biochemical findings.", "content": "Serum parathormone (S-PTH), total and free fractions of serum calcium (Cat and Caf), urinary excretion of cyclic 3',5'-adenosine monophosphate (cAMPu), serum phosphate and serum magnesium were analysed in 68 patients with hyperparathyroidism verified by operation and PAD. The diagnostic significance of the analyses was examined. It was shown that Caf was consistently above normal even in patients in whom the other tests were normal. The best diagnostic sensitivity was thus found for Caf followed by Cat, S-PTH and cAMPu. The results of these tests were generally correlated to each other except in patients with impaired renal function in whom S-PTH increased out of porportion to the other tests. Cat and Caf were significantly correlated to each other. However, Caf was pathologic even when Cat was normal. It is concluded that for hypercalcemic patients Cat and Caf are the most reliable tests. S-PTH is elevated only in some hypercalcemic patients. In normocalcemic patients all tests except Caf show normal values.", "contents": "Grouping of patients with hyperparathyroidism by clinical signs, correlated to some biochemical findings. Serum parathormone (S-PTH), total and free fractions of serum calcium (Cat and Caf), urinary excretion of cyclic 3',5'-adenosine monophosphate (cAMPu), serum phosphate and serum magnesium were analysed in 68 patients with hyperparathyroidism verified by operation and PAD. The diagnostic significance of the analyses was examined. It was shown that Caf was consistently above normal even in patients in whom the other tests were normal. The best diagnostic sensitivity was thus found for Caf followed by Cat, S-PTH and cAMPu. The results of these tests were generally correlated to each other except in patients with impaired renal function in whom S-PTH increased out of porportion to the other tests. Cat and Caf were significantly correlated to each other. However, Caf was pathologic even when Cat was normal. It is concluded that for hypercalcemic patients Cat and Caf are the most reliable tests. S-PTH is elevated only in some hypercalcemic patients. In normocalcemic patients all tests except Caf show normal values."}
{"id": "PMID:202129", "title": "Isolated gastric involvement in Crohn's disease. Report of a case simulating scirrhus carcinoma.", "content": "A 63-year-old woman suffered a short period of nausea and vomiting. X-ray examination of the upper gastrointestinal tract was suspicious of scirrhus carcinoma of the stomach. At operation the suspicion was strengthened, and total gastrectomy was performed. Microscopic examination showed chronic, granulomatous gastritis compatible with Crohn's disease. The patient died on the 8th day postoperatively with caval thrombosis obliterating the inlet to the right auricle. No other localization of the disease could be demonstrated on thorough microscopic and macroscopic examination of the whole gastrointestinal tract.", "contents": "Isolated gastric involvement in Crohn's disease. Report of a case simulating scirrhus carcinoma. A 63-year-old woman suffered a short period of nausea and vomiting. X-ray examination of the upper gastrointestinal tract was suspicious of scirrhus carcinoma of the stomach. At operation the suspicion was strengthened, and total gastrectomy was performed. Microscopic examination showed chronic, granulomatous gastritis compatible with Crohn's disease. The patient died on the 8th day postoperatively with caval thrombosis obliterating the inlet to the right auricle. No other localization of the disease could be demonstrated on thorough microscopic and macroscopic examination of the whole gastrointestinal tract."}
{"id": "PMID:202132", "title": "Cyclic AMP and cyclic GMP accumulation in hamster pre-ovulatory follicles stimulated with LH and FSH.", "content": "Cyclic AMP and cyclic GMP accumulation in hamster pre-ovulatory follicles was determined after in vitro stimulation by LH and FSH. Combined time course and dose response experiments determined that the acute response of the follicles (0-30 min) to LH and FSH was similar with respect to cyclic AMP accumulation. The pattern of cyclic GMP accumulation was, however, distinctly different in LH and FSH stimulated follicles. LH increased follicular cyclic GMP only at the lowest dose (0.005 IU/ml), while higher doses of LH had no effect. In contrast, FSH at all doses stimulated cyclic GMP accumulation. The different cyclic AMP to cyclic relationships generated in the follicles by LH and FSH may be determinants in specificity of hormone action in pre-ovulatory follicles.", "contents": "Cyclic AMP and cyclic GMP accumulation in hamster pre-ovulatory follicles stimulated with LH and FSH. Cyclic AMP and cyclic GMP accumulation in hamster pre-ovulatory follicles was determined after in vitro stimulation by LH and FSH. Combined time course and dose response experiments determined that the acute response of the follicles (0-30 min) to LH and FSH was similar with respect to cyclic AMP accumulation. The pattern of cyclic GMP accumulation was, however, distinctly different in LH and FSH stimulated follicles. LH increased follicular cyclic GMP only at the lowest dose (0.005 IU/ml), while higher doses of LH had no effect. In contrast, FSH at all doses stimulated cyclic GMP accumulation. The different cyclic AMP to cyclic relationships generated in the follicles by LH and FSH may be determinants in specificity of hormone action in pre-ovulatory follicles."}
{"id": "PMID:202133", "title": "Induction of premature parturition in sheep: adrenocorticotrophin and corticosteroid changes during infusion of Synacthen into the foetus.", "content": "Synacthen (10 microgram/h) infused into foetal sheep at about day 125 of gestation caused premature delivery within 4 days. During the first 24 h of the infusion the secretion of adrenocorticotrophin was depressed and the assayable hormone concentration was within 500-1000 pg/ml. Subsequently, large fluctuations occurred in the adrenocorticotrophin concentration in the plasma of foetal sheep which were consistent with the stimulation of adrenocorticotrophin secretion. No transfer of Synachthen to non-infused twin foetuses was observed. The plasma corticosteroid concentration in the infused foetus also showed a small rise during the first 24 h of the infusion followed by large fluctuations in concentrations that coincided with the changes in adrenocorticotrophin. No consistent changes in the plasma corticosteroid concentration in the non-infused twin foetus were observed. These results are discussed in relation to the hormone changes occurring during normal delivery.", "contents": "Induction of premature parturition in sheep: adrenocorticotrophin and corticosteroid changes during infusion of Synacthen into the foetus. Synacthen (10 microgram/h) infused into foetal sheep at about day 125 of gestation caused premature delivery within 4 days. During the first 24 h of the infusion the secretion of adrenocorticotrophin was depressed and the assayable hormone concentration was within 500-1000 pg/ml. Subsequently, large fluctuations occurred in the adrenocorticotrophin concentration in the plasma of foetal sheep which were consistent with the stimulation of adrenocorticotrophin secretion. No transfer of Synachthen to non-infused twin foetuses was observed. The plasma corticosteroid concentration in the infused foetus also showed a small rise during the first 24 h of the infusion followed by large fluctuations in concentrations that coincided with the changes in adrenocorticotrophin. No consistent changes in the plasma corticosteroid concentration in the non-infused twin foetus were observed. These results are discussed in relation to the hormone changes occurring during normal delivery."}
{"id": "PMID:202134", "title": "Adrenocorticotrophin and corticosteroid changes during dexamethasone infusion to intact and synacthen infusion to hypophysectomized foetuses.", "content": "Synacthen has been infused at 10 microgram/h into 4 hypophysectomized foetal sheep. This caused a rise in adrenocorticotrophin to a mean value of 512 pg/ml which remained fairly constant and did not show the large fluctuations seen on infusion into intact foetuses. The Synacthen half-life in the circulation had a mean value of 0.27 min. Hypophysectomy did not necessarily delay the foetal corticosteroid response to Synacthen infusion. The corticosteroid concentration achieved had a mean value of about 50 ng/ml which is substantially below that for intact foetuses and in one case it was maintained at only 20 ng/ml. Despite this delivery occurred within 5 days. Dexamethasone infusion reduced the plasma adrenocorticotrophin concentration by about 70% and the plasma cortisol concentration by about 60%.", "contents": "Adrenocorticotrophin and corticosteroid changes during dexamethasone infusion to intact and synacthen infusion to hypophysectomized foetuses. Synacthen has been infused at 10 microgram/h into 4 hypophysectomized foetal sheep. This caused a rise in adrenocorticotrophin to a mean value of 512 pg/ml which remained fairly constant and did not show the large fluctuations seen on infusion into intact foetuses. The Synacthen half-life in the circulation had a mean value of 0.27 min. Hypophysectomy did not necessarily delay the foetal corticosteroid response to Synacthen infusion. The corticosteroid concentration achieved had a mean value of about 50 ng/ml which is substantially below that for intact foetuses and in one case it was maintained at only 20 ng/ml. Despite this delivery occurred within 5 days. Dexamethasone infusion reduced the plasma adrenocorticotrophin concentration by about 70% and the plasma cortisol concentration by about 60%."}
{"id": "PMID:202136", "title": "Activity of phosphatases and succinic dehydrogenase in the trigeminal ganglion of the corticosteroid-treated mouse.", "content": "Immature mice were treated for 21 days with daily doses of triamcinolone diacetate. The trigeminal ganglion was studied enzymatically for the activity of alkaline phosphatase, acid phosphatase, ATPase and succinic dehydrogenase. It became apparent that the prolonged treatment with a potent corticosteroid hormone did not affect significantly the in vivo activity of the above enzymes. Some enzymes even appeared to have increased their intracellular activity. The heterogeneous effect of corticosteroid upon their peripheral target organs is discussed.", "contents": "Activity of phosphatases and succinic dehydrogenase in the trigeminal ganglion of the corticosteroid-treated mouse. Immature mice were treated for 21 days with daily doses of triamcinolone diacetate. The trigeminal ganglion was studied enzymatically for the activity of alkaline phosphatase, acid phosphatase, ATPase and succinic dehydrogenase. It became apparent that the prolonged treatment with a potent corticosteroid hormone did not affect significantly the in vivo activity of the above enzymes. Some enzymes even appeared to have increased their intracellular activity. The heterogeneous effect of corticosteroid upon their peripheral target organs is discussed."}
{"id": "PMID:202137", "title": "Evidence for neurosecretory substance in neurons in the small intestine of dogs.", "content": "Paraffin-embedded sections from the small intestine of the dog were stained for neurosecretory by various methods. Neurons in the submucous plexus show distinct violet granules, indicating the presence of neurosecretory substance. Nerve cells positive to Gomori's stain were not seen in the myenteric plexus.", "contents": "Evidence for neurosecretory substance in neurons in the small intestine of dogs. Paraffin-embedded sections from the small intestine of the dog were stained for neurosecretory by various methods. Neurons in the submucous plexus show distinct violet granules, indicating the presence of neurosecretory substance. Nerve cells positive to Gomori's stain were not seen in the myenteric plexus."}
{"id": "PMID:202138", "title": "Enzyme activity in the pulp following preparation of cavities and insertion of medicaments in cavities in monkey teeth.", "content": "The effect of cavity preparation, calcium hydroxide and a corticosteroid on pulpal enzymes (Alkaline phosphatase, acid phosphatase, beta-glucuronidase, cytochrome oxidase and succinate, lactate and glucose-6-phosphate dehydrogenase) in monkey teeth has been studied by histochemical means. Cavity preparation with an air turbine and sufficient spray apparently did not affect the enzyme activity of the pulp, nor did application of a corticosteroid to the cavity floor. Twenty-four hours after calcium hydroxide application an increase in enzyme activity was found in the ondontoblastic and subodontoblastic cell layers subjacent to the calcium hydroxide-covered dentin. This activity seemed to demonstrate an onset of dentin formation, and 15 days after the application a slight amount of secondary dentin was found subjacent to the cavities in these teeth.", "contents": "Enzyme activity in the pulp following preparation of cavities and insertion of medicaments in cavities in monkey teeth. The effect of cavity preparation, calcium hydroxide and a corticosteroid on pulpal enzymes (Alkaline phosphatase, acid phosphatase, beta-glucuronidase, cytochrome oxidase and succinate, lactate and glucose-6-phosphate dehydrogenase) in monkey teeth has been studied by histochemical means. Cavity preparation with an air turbine and sufficient spray apparently did not affect the enzyme activity of the pulp, nor did application of a corticosteroid to the cavity floor. Twenty-four hours after calcium hydroxide application an increase in enzyme activity was found in the ondontoblastic and subodontoblastic cell layers subjacent to the calcium hydroxide-covered dentin. This activity seemed to demonstrate an onset of dentin formation, and 15 days after the application a slight amount of secondary dentin was found subjacent to the cavities in these teeth."}
{"id": "PMID:202139", "title": "Ocular herpes simplex infection. A clinical evaluation of virus isolation and studies on iodo-deoxyuridine resistance.", "content": "Fifty-seven patients with ocular herpes simplex (HS) infection were studied for evaluation of existing methods for virus isolation and its application in diagnosis of HS infection. Virus was isolated in 90% of 34 cases with keratitis dendritica, when specimens were taken within eight days of onset of symptoms. The same isolation frequency was obtained in 10 cases of palpebral herpes with conjunctivitis. No isolation was possible in 11 cases of keratitis disciformis. Laboratory confirmation was obtained within four days in 70% of the positive cases. Ten strains of HS virus type 1 were examined for IDU resistance, 5 strains isolated prior to and 5 during IDU treatment. Nine of the strains had the same degree of sensitivity. One strain isolated during treatment was found to be highly resistant.", "contents": "Ocular herpes simplex infection. A clinical evaluation of virus isolation and studies on iodo-deoxyuridine resistance. Fifty-seven patients with ocular herpes simplex (HS) infection were studied for evaluation of existing methods for virus isolation and its application in diagnosis of HS infection. Virus was isolated in 90% of 34 cases with keratitis dendritica, when specimens were taken within eight days of onset of symptoms. The same isolation frequency was obtained in 10 cases of palpebral herpes with conjunctivitis. No isolation was possible in 11 cases of keratitis disciformis. Laboratory confirmation was obtained within four days in 70% of the positive cases. Ten strains of HS virus type 1 were examined for IDU resistance, 5 strains isolated prior to and 5 during IDU treatment. Nine of the strains had the same degree of sensitivity. One strain isolated during treatment was found to be highly resistant."}
{"id": "PMID:202141", "title": "Selective and non-selective beta-blockade in renin release.", "content": "The effects of two beta-adrenergic receptor blocking drugs, the non-selective propranolol and the beta1selective metoprolol, were studied on hemodynamics and plasma renin activity (PRA) of healthy volunteers in an ergometric exercise test. Oral doses of 160 mg of propranolol and 200 mg of metoprolol were tested against placebo. The drug plasma concentrations were determined. Heart rate and systolic blood pressure were equal and significantly lower during treatment with both active drugs when compared to placebo. The effect of drugs on exercise heart rate was correlated with the logarithm of drug plasma concentration with both propranolol and metoprolol. Propranolol, but not metoprolol, decreased the basal level of PRA. The ergometric exercise induced a significant rise in PRA after placebo but this increase was partially inhibited by the both active drugs. On the basis of these findings it is suggested that in man the basal level of PRA could be decreased mainly by blocking the beta2-adrenoceptors. Instead the exercise induced increase of PRA could be inhibited by blocking the beta1-adrenergic receptors.", "contents": "Selective and non-selective beta-blockade in renin release. The effects of two beta-adrenergic receptor blocking drugs, the non-selective propranolol and the beta1selective metoprolol, were studied on hemodynamics and plasma renin activity (PRA) of healthy volunteers in an ergometric exercise test. Oral doses of 160 mg of propranolol and 200 mg of metoprolol were tested against placebo. The drug plasma concentrations were determined. Heart rate and systolic blood pressure were equal and significantly lower during treatment with both active drugs when compared to placebo. The effect of drugs on exercise heart rate was correlated with the logarithm of drug plasma concentration with both propranolol and metoprolol. Propranolol, but not metoprolol, decreased the basal level of PRA. The ergometric exercise induced a significant rise in PRA after placebo but this increase was partially inhibited by the both active drugs. On the basis of these findings it is suggested that in man the basal level of PRA could be decreased mainly by blocking the beta2-adrenoceptors. Instead the exercise induced increase of PRA could be inhibited by blocking the beta1-adrenergic receptors."}
{"id": "PMID:202144", "title": "Effect of endurance training on the capacity of red and white skeletal muscle of mouse to oxidize carboxyl-14C-labelled palmitate.", "content": "Three groups of mice were trained for 1, 4 and 5 months according to different running programs on a motor driven treadmill and the fatty acid oxidation capacity (FAO) and the activities of some enzymes of energy metabolism (cytochrome c oxidase, malate dehydrogenase, triosephosphate dehydrogenase, and lactate dehydrogenase) were determined from m. quadriceps femoris (MQF). Endurance training increased the FAO [5-month training 4 days/week, 30 min/day 22% (p less than 0.05); 1-month training, 7 days/week, 150 min/day 37% (p less than 0.001); 4-month training, 5 days/week, 60 min/day 24% (p less than 0.05)]. The activities of cytochrome c oxidase and malate dehydrogenase increased approx. 30% (p less than 0.001) whereas triosephosphate dehydrogenase and lactate dehydrogenase activities were not prominently influenced by training. The predominantly red part of MQF of untrained animals oxidized palmitate four times faster than the predominantly white part. The activities of cytochrome c oxidase and malate dehydrogenase were two times higher showing pronounced FAO in the red part. Endurance training increased the FAO and activities of oxidative enzymes in the red and white parts and in the whole muscle relatively equally resulting in similar differences between the muscle types after training. The absolute increase in the FAO of the red muscle was, however, manyfold when compared in chemical units to the white muscle.", "contents": "Effect of endurance training on the capacity of red and white skeletal muscle of mouse to oxidize carboxyl-14C-labelled palmitate. Three groups of mice were trained for 1, 4 and 5 months according to different running programs on a motor driven treadmill and the fatty acid oxidation capacity (FAO) and the activities of some enzymes of energy metabolism (cytochrome c oxidase, malate dehydrogenase, triosephosphate dehydrogenase, and lactate dehydrogenase) were determined from m. quadriceps femoris (MQF). Endurance training increased the FAO [5-month training 4 days/week, 30 min/day 22% (p less than 0.05); 1-month training, 7 days/week, 150 min/day 37% (p less than 0.001); 4-month training, 5 days/week, 60 min/day 24% (p less than 0.05)]. The activities of cytochrome c oxidase and malate dehydrogenase increased approx. 30% (p less than 0.001) whereas triosephosphate dehydrogenase and lactate dehydrogenase activities were not prominently influenced by training. The predominantly red part of MQF of untrained animals oxidized palmitate four times faster than the predominantly white part. The activities of cytochrome c oxidase and malate dehydrogenase were two times higher showing pronounced FAO in the red part. Endurance training increased the FAO and activities of oxidative enzymes in the red and white parts and in the whole muscle relatively equally resulting in similar differences between the muscle types after training. The absolute increase in the FAO of the red muscle was, however, manyfold when compared in chemical units to the white muscle."}
{"id": "PMID:202145", "title": "Role of the adrenergic nervous system in development of training-induced bradycardia.", "content": "Sprague-Dawley rats, normal and chemically sympathectomized with 6-hydroxy-dopamine, were trained by treadmill running. The normal rats, unlike the sympathectomized animals, showed reduction of the exercise heart rate after the training period. Compared to a sedentary control group the sympathectomized rats showed no difference in intrinsic heart rate after pithing and denervation and no increase in heart weight. The increase of the heart weight/body weight ratio after training was smaller in the sympathectomized group than in the normal one. The results show that a functioning adrenergic nervous system is necessary for an efficient adaptation to physical training. Administration of noradrenaline to pithed trained and untrained rats showed that betaadrenergic receptor sensitivity was not altered by physical training. The intrinsic heart rate of normal trained rats was lower than that of normal control rats.", "contents": "Role of the adrenergic nervous system in development of training-induced bradycardia. Sprague-Dawley rats, normal and chemically sympathectomized with 6-hydroxy-dopamine, were trained by treadmill running. The normal rats, unlike the sympathectomized animals, showed reduction of the exercise heart rate after the training period. Compared to a sedentary control group the sympathectomized rats showed no difference in intrinsic heart rate after pithing and denervation and no increase in heart weight. The increase of the heart weight/body weight ratio after training was smaller in the sympathectomized group than in the normal one. The results show that a functioning adrenergic nervous system is necessary for an efficient adaptation to physical training. Administration of noradrenaline to pithed trained and untrained rats showed that betaadrenergic receptor sensitivity was not altered by physical training. The intrinsic heart rate of normal trained rats was lower than that of normal control rats."}
{"id": "PMID:202147", "title": "Opiate receptors and endogenous opioid peptides in tolerance and dependence.", "content": "The impact of the discovery of the endogenous opioid peptides, the enkephalins and endorphins, on our concepts of the mechanisms of tolerance to, and dependence on, opiates is discussed. After a brief survey of the chemistry of the opioid peptides, the possibility of an interaction between opiates and the peptides is considered and a hypothesis formulated. Experimental proof is presented as far as it has become available. The possible mechanisms involved in the development of tolerance and dependence for alcohol, barbiturates and opiates are compared briefly.", "contents": "Opiate receptors and endogenous opioid peptides in tolerance and dependence. The impact of the discovery of the endogenous opioid peptides, the enkephalins and endorphins, on our concepts of the mechanisms of tolerance to, and dependence on, opiates is discussed. After a brief survey of the chemistry of the opioid peptides, the possibility of an interaction between opiates and the peptides is considered and a hypothesis formulated. Experimental proof is presented as far as it has become available. The possible mechanisms involved in the development of tolerance and dependence for alcohol, barbiturates and opiates are compared briefly."}
{"id": "PMID:202150", "title": "Importance of cardiac and vascular beta-receptors in the action of phentolamine.", "content": "To determine to what extent the effects of phentolamine (PHE) are mediated by the cardiac and vascular beta-receptors, the action of the drug was studied in anaesthetized cats pretreated with beta-blockers. Blockade of the cardiac beta-receptors with either propranolol or metoprolol entirely prevented the increases in heart rate, dP/dt and cardiac output caused by PHE. In animals pretreated with propranolol (in a dose blocking the vascular beta-receptors) or metoprolol (in a purely cardio-selective dose) PHE significantly lowered blood pressure to the same extent as in untreated controls. The effects of PHE on the heart are thus conditional on the integrity of cardiac beta-receptors, whereas it seems improbable that vascular beta-receptors have any part in its vasodilative action. Evidence presented in the literature rather suggests a predominantly central mode of action.", "contents": "Importance of cardiac and vascular beta-receptors in the action of phentolamine. To determine to what extent the effects of phentolamine (PHE) are mediated by the cardiac and vascular beta-receptors, the action of the drug was studied in anaesthetized cats pretreated with beta-blockers. Blockade of the cardiac beta-receptors with either propranolol or metoprolol entirely prevented the increases in heart rate, dP/dt and cardiac output caused by PHE. In animals pretreated with propranolol (in a dose blocking the vascular beta-receptors) or metoprolol (in a purely cardio-selective dose) PHE significantly lowered blood pressure to the same extent as in untreated controls. The effects of PHE on the heart are thus conditional on the integrity of cardiac beta-receptors, whereas it seems improbable that vascular beta-receptors have any part in its vasodilative action. Evidence presented in the literature rather suggests a predominantly central mode of action."}
{"id": "PMID:202154", "title": "Ether-dissolved ethiodol for lymphangiography: an experimental study.", "content": "In order to decrease administration time, the viscosity of Ethiodol was reduced by mixing it with ether; this mixture was evaluated in lymphangiography of dogs. The ether-Ethiodol solution was injected into a cannulated lymph vessel of one hind limb and compared to pure Ethiodol in the other. For the ether-Ethiodol solution, the time required for complete injection was 10-30 min in most cases compared to 60-105 min for Ethiodol alone. The radiographic appearance of the lymph vessels and nodes appeared similar on both sides, and follow-up lymphangiograms in two animals after 1 and 3 weeks showed no difference from the original study. Microscopic examination of the opacified lymph nodes on both sides revealed no histologic differences. The techniques has potential clinical application.", "contents": "Ether-dissolved ethiodol for lymphangiography: an experimental study. In order to decrease administration time, the viscosity of Ethiodol was reduced by mixing it with ether; this mixture was evaluated in lymphangiography of dogs. The ether-Ethiodol solution was injected into a cannulated lymph vessel of one hind limb and compared to pure Ethiodol in the other. For the ether-Ethiodol solution, the time required for complete injection was 10-30 min in most cases compared to 60-105 min for Ethiodol alone. The radiographic appearance of the lymph vessels and nodes appeared similar on both sides, and follow-up lymphangiograms in two animals after 1 and 3 weeks showed no difference from the original study. Microscopic examination of the opacified lymph nodes on both sides revealed no histologic differences. The techniques has potential clinical application."}
{"id": "PMID:202155", "title": "Computed tomography in the evaluation of sarcomatous tumors of the thigh.", "content": "CT examination of a soft tissue mass in the lower extremity adds substantially to a more precise preoperative histologic diagnosis and anatomic localization of the lesion. An appreciation of the normal cross-sectional anatomy of this region is essential for adequate evaluation of the information provided by the CT scan. Four patients with sarcomatous tumors involving the soft tissues of the thigh are described and the diagnostic information provided by CT is discussed. In two of these cases anatomic cross sections are correlated with the CT scan.", "contents": "Computed tomography in the evaluation of sarcomatous tumors of the thigh. CT examination of a soft tissue mass in the lower extremity adds substantially to a more precise preoperative histologic diagnosis and anatomic localization of the lesion. An appreciation of the normal cross-sectional anatomy of this region is essential for adequate evaluation of the information provided by the CT scan. Four patients with sarcomatous tumors involving the soft tissues of the thigh are described and the diagnostic information provided by CT is discussed. In two of these cases anatomic cross sections are correlated with the CT scan."}
{"id": "PMID:202156", "title": "False negative bone scans in neuroblastoma metastatic to the ends of long bones.", "content": "Studies of 12 children with neuroblastoma were performed to assess the comparative sensitivity of skeletal radiography and 99mTc pyrophosphate bone scintigraphy in the detection of metastases to the ends of long bones. A total of 18 lesions were detected in six patients. Fourteen were demonstrated only by radiography, whereas four were positive by both methods. In no case was a lesion detected by scintigraphy alone. Small lesion size, lytic radiographic appearance, metaphyseal location, and technical difficulties in imaging the knee all contribute to the high incidenmce of false negative scans. Lesions in two of the nine patients with metastatic disease to bone would have been missed on the basis of bone scans alone. Accordingly, the radiographic skeletal survey seems to remain a necessary part of the neuroblastoma workup.", "contents": "False negative bone scans in neuroblastoma metastatic to the ends of long bones. Studies of 12 children with neuroblastoma were performed to assess the comparative sensitivity of skeletal radiography and 99mTc pyrophosphate bone scintigraphy in the detection of metastases to the ends of long bones. A total of 18 lesions were detected in six patients. Fourteen were demonstrated only by radiography, whereas four were positive by both methods. In no case was a lesion detected by scintigraphy alone. Small lesion size, lytic radiographic appearance, metaphyseal location, and technical difficulties in imaging the knee all contribute to the high incidenmce of false negative scans. Lesions in two of the nine patients with metastatic disease to bone would have been missed on the basis of bone scans alone. Accordingly, the radiographic skeletal survey seems to remain a necessary part of the neuroblastoma workup."}
{"id": "PMID:202157", "title": "Radiologic appearance of viral disease of the lower respiratory tract in infants and children.", "content": "The radiologic findings in 123 hospitalized children with viral disease of the respiratory tract due to adenovirus, respiratory syncytial virus, parainfluenza, influenza, measles, or herpes virus were retrospectively reviewed. Bronchial wall thickening, peribronchial shadowing and/or associated perihilar streaking were present in 107 cases. Patchy pulmonary shadowing thought to reflect disease at a sublobular or lobular level was present in 72 cases, while areas of coalescent more homogeneous pulmonary shadowing were present in only 20 cases. In general the pulmonary abnormalities were widespread; on the average, two to three lobes demonstrated abnormal pulmonary findings. Poorly defined small pulmonary nodules, while radiologically unimpressive, were noted in 49 cases. Air trapping was observed in 61 cases. Hilar adenopathy was seen in only four cases and was unimpressive. There was a striking absence of pleural effusion, pneumothorax, pneumatocele, and lung abscess in the patients examined.", "contents": "Radiologic appearance of viral disease of the lower respiratory tract in infants and children. The radiologic findings in 123 hospitalized children with viral disease of the respiratory tract due to adenovirus, respiratory syncytial virus, parainfluenza, influenza, measles, or herpes virus were retrospectively reviewed. Bronchial wall thickening, peribronchial shadowing and/or associated perihilar streaking were present in 107 cases. Patchy pulmonary shadowing thought to reflect disease at a sublobular or lobular level was present in 72 cases, while areas of coalescent more homogeneous pulmonary shadowing were present in only 20 cases. In general the pulmonary abnormalities were widespread; on the average, two to three lobes demonstrated abnormal pulmonary findings. Poorly defined small pulmonary nodules, while radiologically unimpressive, were noted in 49 cases. Air trapping was observed in 61 cases. Hilar adenopathy was seen in only four cases and was unimpressive. There was a striking absence of pleural effusion, pneumothorax, pneumatocele, and lung abscess in the patients examined."}
{"id": "PMID:202158", "title": "The nasal arteries.", "content": "Thorough knowledge of the normal gross and radiographic anatomy of the nasal fossa is a prerequisite for correct interpretation of external carotid angiograms in patients with lesions in or adjacent to the nasal cavity. This report describes in detail the normal gross and angiographic vascular anatomy of the nasal fossa. The appearance of the sphenopalatine artery and nasal branches of the ethmoidal arteries in a variety of lesions that affect the nasal cavity, nasopharynx, and adjacent structures is also discussed. Typical changes in acute rhinitis, sinusitis, sphenopalatine neuralgia, vascular malformations, neoplasms, and benign bulky nasal masses are illustrated.", "contents": "The nasal arteries. Thorough knowledge of the normal gross and radiographic anatomy of the nasal fossa is a prerequisite for correct interpretation of external carotid angiograms in patients with lesions in or adjacent to the nasal cavity. This report describes in detail the normal gross and angiographic vascular anatomy of the nasal fossa. The appearance of the sphenopalatine artery and nasal branches of the ethmoidal arteries in a variety of lesions that affect the nasal cavity, nasopharynx, and adjacent structures is also discussed. Typical changes in acute rhinitis, sinusitis, sphenopalatine neuralgia, vascular malformations, neoplasms, and benign bulky nasal masses are illustrated."}
{"id": "PMID:202160", "title": "Effect of vitamin E on serum cholesterol and triglycerides in hyperlipidemic patients treated with diet and clofibrate.", "content": "Vitamin E in conventional therapeutic doses (400 mg/day) was given to 17 patients with hyperlipidemia on long-term treatment with diets enriched in polyunsaturated fatty acids and with clofibrate. The effect of this treatment on total serum cholesterol and on serum triglycerides was studied. To avoid influences of other factors (especially changes in dietary habits) the investigation was performed giving the patients tocopherol and placebo randomly, double blind and cross-over. No significant effect of vitamin E on total serum cholesterol or on serum triglycerides was seen.", "contents": "Effect of vitamin E on serum cholesterol and triglycerides in hyperlipidemic patients treated with diet and clofibrate. Vitamin E in conventional therapeutic doses (400 mg/day) was given to 17 patients with hyperlipidemia on long-term treatment with diets enriched in polyunsaturated fatty acids and with clofibrate. The effect of this treatment on total serum cholesterol and on serum triglycerides was studied. To avoid influences of other factors (especially changes in dietary habits) the investigation was performed giving the patients tocopherol and placebo randomly, double blind and cross-over. No significant effect of vitamin E on total serum cholesterol or on serum triglycerides was seen."}
{"id": "PMID:202161", "title": "Androluteoma syndrome of pregnancy.", "content": "The clinical course of a 26-year-old primigravid woman with a virilizing luteoma of pregnancy is described. It was demonstrated by endocrine studies that the tumor secreted an excessive amount of testosterone. After removal of the luteoma in week 32 of pregnancy, the virilizing symptoms of the mother completely regressed. A normal male infant was delivered in week 39. From 100 luteomas of pregnancy described in the literature, 26 cases have been cited to elicit endocrine virilizing activity. An evaluative synopsis indicates that including the case described in this paper only 13 can be regarded as a clinical, morphologic, and functional entity. This entity should be differentiated from the inhomogeneous group of luteomas as the \"androluteoma syndrome of pregnancy.\" It is characterized by the following major criteria: virilization, beginning with the second trimester of pregnancy; histologic criteria of a luteoma of pregnancy; production of testosterone, leading to excessive plasma levels (exceeding the concentration of androstenedione), and masculinization of female fetuses.", "contents": "Androluteoma syndrome of pregnancy. The clinical course of a 26-year-old primigravid woman with a virilizing luteoma of pregnancy is described. It was demonstrated by endocrine studies that the tumor secreted an excessive amount of testosterone. After removal of the luteoma in week 32 of pregnancy, the virilizing symptoms of the mother completely regressed. A normal male infant was delivered in week 39. From 100 luteomas of pregnancy described in the literature, 26 cases have been cited to elicit endocrine virilizing activity. An evaluative synopsis indicates that including the case described in this paper only 13 can be regarded as a clinical, morphologic, and functional entity. This entity should be differentiated from the inhomogeneous group of luteomas as the \"androluteoma syndrome of pregnancy.\" It is characterized by the following major criteria: virilization, beginning with the second trimester of pregnancy; histologic criteria of a luteoma of pregnancy; production of testosterone, leading to excessive plasma levels (exceeding the concentration of androstenedione), and masculinization of female fetuses."}
{"id": "PMID:202162", "title": "Fibrous histiocytoma of the tarsus.", "content": "A 21-year-old white man had an asymptomatic eyelid mass that had slowly enlarged for one year. On clinical examination the lesion was well circumscribed; it appeared subconjunctivally but provoked no conjunctival inflammation, and had a consistency suggestive of cartilage. Microscopic examination showed it was matted and composed of elongated fibro-histiocytes and an evenly distributed population of xanthoma cells and Touton giant cells. The lesion was easily removed by local excision because of a pseudocapsule formed by remnants of the tarsus; there has been no recurrence during a 12-month follow-up.", "contents": "Fibrous histiocytoma of the tarsus. A 21-year-old white man had an asymptomatic eyelid mass that had slowly enlarged for one year. On clinical examination the lesion was well circumscribed; it appeared subconjunctivally but provoked no conjunctival inflammation, and had a consistency suggestive of cartilage. Microscopic examination showed it was matted and composed of elongated fibro-histiocytes and an evenly distributed population of xanthoma cells and Touton giant cells. The lesion was easily removed by local excision because of a pseudocapsule formed by remnants of the tarsus; there has been no recurrence during a 12-month follow-up."}
{"id": "PMID:202163", "title": "Mesectodermal leiomyosarcoma of the antrum and orbit.", "content": "A 39-year-old black man developed a left antral leiomyosarcoma that subsequently extended into the ipsilateral orbit. On light microscopic appearance of the antral tumor the presence of a distinctive myxoid and fibrillar cytoplasmic background suggested the diagnosis of a malignant Schwann's cell tumor. A second biopsy of the orbital extension displayed the same fibrillar character, but the emergence of tumor giant cells with cytoplasmic trichrome positivity also raised the possibility of a rhabdomyosarcoma. Electron microscopy demonstrated the smooth muscle derivation of the tumor, which probably originated from vascular smooth muscle elements. The atypical neural appearance of this myogenous tumor may have been caused by the extensive neural crest contribution to the cephalic connective tissues (mesectoderm). Radiation therapy and chemotherapy were ineffective.", "contents": "Mesectodermal leiomyosarcoma of the antrum and orbit. A 39-year-old black man developed a left antral leiomyosarcoma that subsequently extended into the ipsilateral orbit. On light microscopic appearance of the antral tumor the presence of a distinctive myxoid and fibrillar cytoplasmic background suggested the diagnosis of a malignant Schwann's cell tumor. A second biopsy of the orbital extension displayed the same fibrillar character, but the emergence of tumor giant cells with cytoplasmic trichrome positivity also raised the possibility of a rhabdomyosarcoma. Electron microscopy demonstrated the smooth muscle derivation of the tumor, which probably originated from vascular smooth muscle elements. The atypical neural appearance of this myogenous tumor may have been caused by the extensive neural crest contribution to the cephalic connective tissues (mesectoderm). Radiation therapy and chemotherapy were ineffective."}
{"id": "PMID:202164", "title": "Immunohistochemical and ultrastructural analysis of medullary carcinoma of the thyroid in relation to hormone production.", "content": "Eighteen cases of medullary carcinoma of the thyroid were analyzed immunohistochemically for calcitonin- and ACTH-containing cells, and tumor cells in 8 cases were examined by an electron microscope and analyzed by manual and computer procedures with particular attention paid to the size and quality of secretory granules. Calcitonin- and ACTH-containing cells were found singly or in clusters in 14 and 11 tumors, respectively. In 4 cases, calcitonin-positive cell clusters and an increase in number of singly scattered C cells were seen apart from the main tumor, suggesting a multicentric nature of certain medullary carcinomas. Some ACTH-containing cells were apparently also positive for calcitonin. In a case of familial Sipple disease, follicular lining cells were replaced in areas with ACTH-containing cells. Three to five frequency distribution curves of the size of secretory granules were obtained in all of 6 cases analyzed, and at least two different types of granule matrix were identified.", "contents": "Immunohistochemical and ultrastructural analysis of medullary carcinoma of the thyroid in relation to hormone production. Eighteen cases of medullary carcinoma of the thyroid were analyzed immunohistochemically for calcitonin- and ACTH-containing cells, and tumor cells in 8 cases were examined by an electron microscope and analyzed by manual and computer procedures with particular attention paid to the size and quality of secretory granules. Calcitonin- and ACTH-containing cells were found singly or in clusters in 14 and 11 tumors, respectively. In 4 cases, calcitonin-positive cell clusters and an increase in number of singly scattered C cells were seen apart from the main tumor, suggesting a multicentric nature of certain medullary carcinomas. Some ACTH-containing cells were apparently also positive for calcitonin. In a case of familial Sipple disease, follicular lining cells were replaced in areas with ACTH-containing cells. Three to five frequency distribution curves of the size of secretory granules were obtained in all of 6 cases analyzed, and at least two different types of granule matrix were identified."}
{"id": "PMID:202165", "title": "The stability of events in the natural history of neoplasia.", "content": "Previous studies on the natural history of neoplasia, utilizing mouse skin as a model, have demonstrated that the process of epidermal carcinogenesis may be separated into at least two different phases. The first of these, termed \"initiation,\" is essentially irreversible; the second phase, that of promotion, may be modulated or reversed by a variety of environmental conditions. More recently, similar stages have been demonstrated for other organ systems during carcinogenesis, in particular that of murine liver. At the same time, investigations of a variety of systems including those in plants, amphibians, and, most recently, in mammals have demonstrated that the initiation process of neoplasia may not be as irreversible as previously considered, but in several of these systems, including those in plants and in the mouse teratoma, the neoplastic process appears to be reversible from its initial stages under appropriate conditions. A proposed scheme is presented which takes into account the reversibility of the process of initiation in the natural history of neoplasia.", "contents": "The stability of events in the natural history of neoplasia. Previous studies on the natural history of neoplasia, utilizing mouse skin as a model, have demonstrated that the process of epidermal carcinogenesis may be separated into at least two different phases. The first of these, termed \"initiation,\" is essentially irreversible; the second phase, that of promotion, may be modulated or reversed by a variety of environmental conditions. More recently, similar stages have been demonstrated for other organ systems during carcinogenesis, in particular that of murine liver. At the same time, investigations of a variety of systems including those in plants, amphibians, and, most recently, in mammals have demonstrated that the initiation process of neoplasia may not be as irreversible as previously considered, but in several of these systems, including those in plants and in the mouse teratoma, the neoplastic process appears to be reversible from its initial stages under appropriate conditions. A proposed scheme is presented which takes into account the reversibility of the process of initiation in the natural history of neoplasia."}
{"id": "PMID:202166", "title": "The type 1 alveolar lining cells of the mammalian lung. II. In vitro identification via the cell surface and ultrastructure of isolated cells from adult rabbit lung.", "content": "Using a newly described dissociation and isolation technique, Type 1 alveolar lining cells were obtained from adult rabbit lung within a heterogeneous population. Identification of many lung cell types in this mixed population was by a) comparison of isolated cells with in situ lung cells in lung sections using identical parallel staining, b) stepwise ultrastructural examination of cells during all stages of lung dissociation so that intercellular associations were monitored throughout, and c) Type 1 cell surface changes following collagenase treatment. This phenomenon was studied with both electron and light microscopy, the latter employing tetrachrome staining of basophilic blebs as well as characteristic staining of nucleus and cytoplasm. Following their isolation, most Type 1 cells lost their surface blebs and assumed a \"relaxed\" state. In this condition, Type 1 cells were exposed to cytochalasin D (CD) for various times and at several concentrations. Surface knobs, having all the characteristics of zeiotic knobs produced in a number of cultured cell lines by exposure to CD, were produced in isolated Type 1 epithelial cells within 45 minutes. The reaction to CD was temperature-dependent, proceeding maximally at 37 C with inhibition at lower temperatures and was inhibited by antimetabolites such as dinitrophenol and 2-deoxyglucose in the presence of CD. As with established cell lines, formation of zeiotic knobs at the isolated Type 1 cell surface appeared closely related to microfilamentous nets located beneath the plasmalemma. The density of this net appeared to vary as isolated Type 1 cells underwent expansion and contraction in response to CD. Zeiotic knobs were formed as the result of herniation of endoplasm through the cell cortex. The significance of such a labile cortical zone is considered in relation to the deformation changes Type 1 cells undergo during inflation-deflation of alveoli and the folding-unfolding of alveolar lining cells as a result of lung volume changes.", "contents": "The type 1 alveolar lining cells of the mammalian lung. II. In vitro identification via the cell surface and ultrastructure of isolated cells from adult rabbit lung. Using a newly described dissociation and isolation technique, Type 1 alveolar lining cells were obtained from adult rabbit lung within a heterogeneous population. Identification of many lung cell types in this mixed population was by a) comparison of isolated cells with in situ lung cells in lung sections using identical parallel staining, b) stepwise ultrastructural examination of cells during all stages of lung dissociation so that intercellular associations were monitored throughout, and c) Type 1 cell surface changes following collagenase treatment. This phenomenon was studied with both electron and light microscopy, the latter employing tetrachrome staining of basophilic blebs as well as characteristic staining of nucleus and cytoplasm. Following their isolation, most Type 1 cells lost their surface blebs and assumed a \"relaxed\" state. In this condition, Type 1 cells were exposed to cytochalasin D (CD) for various times and at several concentrations. Surface knobs, having all the characteristics of zeiotic knobs produced in a number of cultured cell lines by exposure to CD, were produced in isolated Type 1 epithelial cells within 45 minutes. The reaction to CD was temperature-dependent, proceeding maximally at 37 C with inhibition at lower temperatures and was inhibited by antimetabolites such as dinitrophenol and 2-deoxyglucose in the presence of CD. As with established cell lines, formation of zeiotic knobs at the isolated Type 1 cell surface appeared closely related to microfilamentous nets located beneath the plasmalemma. The density of this net appeared to vary as isolated Type 1 cells underwent expansion and contraction in response to CD. Zeiotic knobs were formed as the result of herniation of endoplasm through the cell cortex. The significance of such a labile cortical zone is considered in relation to the deformation changes Type 1 cells undergo during inflation-deflation of alveoli and the folding-unfolding of alveolar lining cells as a result of lung volume changes."}
{"id": "PMID:202167", "title": "Replication of type I herpes simplex virus in primary cultures of hairy cell leukemic leukocytes.", "content": "The ability of leukemic leukocytes to support the replication of herpes simplex virus (HSV) was studied. Mononuclear leukocytes (MNL) from the peripheral blood of patients with a variety of lymphoid leukemias were isolated on Ficoll-Hypaque gradients and infected with HSV at a multiplicity of infection of 5 to 10. No virus growth was detected in cells from patients with chronic lymphocytic leukemia (9), acute lymphocytic leukemia (1), or lymphosarcoma cell leukemia (2), HSV replication did occur in hairy cell leukemic MNL from all of 4 patients studied. Maximal titers of 10(3.7) to 10(4.7) PFU/ml occurred 1 to 7 days after incubation. By electron microscopy, herpesvirus particles were seen in the nuclei of these infected cells after 3 days of culture, but none was seen in the cells not exposed to virus. Fluorescent antibody examination confirmed the presence of HSV antigens in the nuclei of infected hairy cells. No difference in the adsorption or penetration of the virus was found with the various MNL studied. Productive infection of the cells thus appeared to depend on the ability of the leukocyte ;o support a later stage of infection, either uncoating or replication of the virus.", "contents": "Replication of type I herpes simplex virus in primary cultures of hairy cell leukemic leukocytes. The ability of leukemic leukocytes to support the replication of herpes simplex virus (HSV) was studied. Mononuclear leukocytes (MNL) from the peripheral blood of patients with a variety of lymphoid leukemias were isolated on Ficoll-Hypaque gradients and infected with HSV at a multiplicity of infection of 5 to 10. No virus growth was detected in cells from patients with chronic lymphocytic leukemia (9), acute lymphocytic leukemia (1), or lymphosarcoma cell leukemia (2), HSV replication did occur in hairy cell leukemic MNL from all of 4 patients studied. Maximal titers of 10(3.7) to 10(4.7) PFU/ml occurred 1 to 7 days after incubation. By electron microscopy, herpesvirus particles were seen in the nuclei of these infected cells after 3 days of culture, but none was seen in the cells not exposed to virus. Fluorescent antibody examination confirmed the presence of HSV antigens in the nuclei of infected hairy cells. No difference in the adsorption or penetration of the virus was found with the various MNL studied. Productive infection of the cells thus appeared to depend on the ability of the leukocyte ;o support a later stage of infection, either uncoating or replication of the virus."}
{"id": "PMID:202168", "title": "Isolation of enzymatically homogeneous populations of human lymphocytes, monocytes, and granulocytes by zonal centrifugation.", "content": "Human monocytes, lymphocytes, granulocytes, red cells, and platelets were completely separated from each other by zonal centrifugation on linear sucrose density gradient. The monocytes contained only one tenth the amount of myeloperoxidase, one half the amount of lysozyme, one half the amount of acid ,hosphatase, and one half the amount of beta-glucuronidase found in granulocytes; the monocytes contained no alkaline phosphatase or neutral protease. The lymphocyte fraction contained only acid phosphatase and beta-glucuronidase in amounts one half as much as in the monocytes. Fluctuations in enzyme levels of monocytes and granulocytes were noted following infection. In vitro, the isolated monocytes transformed into macrophages. The results suggest that lymphocytes, monocytes, and granulocytes may be linked biochemically in a differentiation sequence through sets of commonly shared enzymes as well as by groups of enzymes specific for each divergent cell line.", "contents": "Isolation of enzymatically homogeneous populations of human lymphocytes, monocytes, and granulocytes by zonal centrifugation. Human monocytes, lymphocytes, granulocytes, red cells, and platelets were completely separated from each other by zonal centrifugation on linear sucrose density gradient. The monocytes contained only one tenth the amount of myeloperoxidase, one half the amount of lysozyme, one half the amount of acid ,hosphatase, and one half the amount of beta-glucuronidase found in granulocytes; the monocytes contained no alkaline phosphatase or neutral protease. The lymphocyte fraction contained only acid phosphatase and beta-glucuronidase in amounts one half as much as in the monocytes. Fluctuations in enzyme levels of monocytes and granulocytes were noted following infection. In vitro, the isolated monocytes transformed into macrophages. The results suggest that lymphocytes, monocytes, and granulocytes may be linked biochemically in a differentiation sequence through sets of commonly shared enzymes as well as by groups of enzymes specific for each divergent cell line."}
{"id": "PMID:202169", "title": "Role of insulin during exercise-induced glycogenesis in muscle: effect on cyclic AMP.", "content": "Skeletal muscle cyclic AMP (cAMP) content and glycogen synthesis were investigated in male rats subjected to exhaustive exercise, alloxan diabetes, and combinations of these conditions. After an exhaustive swim or control treatment of wading, randomly selected animals were administered 500 mg glucose via stomach tube. Two hours after glucose administration, gastrocnemius glycogen levels rose from 1.31 to 10.67 mg/g wet wt in fatigued nondiabetics (FND), producing a 94% supercompensation above control values. Glycogen of fatigued diabetics (FD) increased from 0.88 to 4.21 mg/g wet wt during the first 2 hr after glucose administration and did not reach control values for 24 h. In conjunction with these glycogen changes, cAMP increased from 1.23 to 2.59 and 1.47 to 2.81 pmol/mg wet wt for FND and FD, respectively (P less than 0.05). No difference in cAMP levels between diabetics and nondiabetics was found. These in vivo data suggest that insulin may not be essential for muscle glycogen synthesis, but that after glycogen depletion it plays a prominent role in supercompensation. Also, this hormone's mechanism of action in skeletal muscle does not appear to be mediated through alteration in the tissue cAMP concentration.", "contents": "Role of insulin during exercise-induced glycogenesis in muscle: effect on cyclic AMP. Skeletal muscle cyclic AMP (cAMP) content and glycogen synthesis were investigated in male rats subjected to exhaustive exercise, alloxan diabetes, and combinations of these conditions. After an exhaustive swim or control treatment of wading, randomly selected animals were administered 500 mg glucose via stomach tube. Two hours after glucose administration, gastrocnemius glycogen levels rose from 1.31 to 10.67 mg/g wet wt in fatigued nondiabetics (FND), producing a 94% supercompensation above control values. Glycogen of fatigued diabetics (FD) increased from 0.88 to 4.21 mg/g wet wt during the first 2 hr after glucose administration and did not reach control values for 24 h. In conjunction with these glycogen changes, cAMP increased from 1.23 to 2.59 and 1.47 to 2.81 pmol/mg wet wt for FND and FD, respectively (P less than 0.05). No difference in cAMP levels between diabetics and nondiabetics was found. These in vivo data suggest that insulin may not be essential for muscle glycogen synthesis, but that after glycogen depletion it plays a prominent role in supercompensation. Also, this hormone's mechanism of action in skeletal muscle does not appear to be mediated through alteration in the tissue cAMP concentration."}
{"id": "PMID:202177", "title": "Immunofluorescent study on egg-adapted avian encephalomyelitis virus infection in chickens.", "content": "Fluorescent antibody study showed persistent infection of egg-adapted avian encephalomyelitis virus in the central nervous system and pancreatic tissues of infected embryos and chickens hatched from them. The limited organ tropism of the egg-adapted virus in hatched chickens was in striking contrast to the systemic infection that occurs with a field strain. In chidkens orally infected with egg-adapted virus strains, transient infection of a few organs was found despite occurrence of viremia.", "contents": "Immunofluorescent study on egg-adapted avian encephalomyelitis virus infection in chickens. Fluorescent antibody study showed persistent infection of egg-adapted avian encephalomyelitis virus in the central nervous system and pancreatic tissues of infected embryos and chickens hatched from them. The limited organ tropism of the egg-adapted virus in hatched chickens was in striking contrast to the systemic infection that occurs with a field strain. In chidkens orally infected with egg-adapted virus strains, transient infection of a few organs was found despite occurrence of viremia."}
{"id": "PMID:202178", "title": "Isolation of bovine adenovirus type 4 from cattle in Oregon.", "content": "Four isolates of bovine adenovirus type 4 were recovered from Oregon cattle. One isolate was recovered from a 1-week-old calf with pneumoenteritis, and 1 isolate from an 8-month-old bull with fever and respiratory disease. Two isolates were recovered as latent viruses in testicular cell cultures. All 4 isolates of the virus were shown to have certain physical, chemical, biologic, and antigenic characteristics similar to previously described strains of bovine adenovirus type 4. Of 246 adult beef and dairy cattle in Oregon, 51% had serum-viral neutralizing antibodies to the type 4 virus at the 1:8 dilution level.", "contents": "Isolation of bovine adenovirus type 4 from cattle in Oregon. Four isolates of bovine adenovirus type 4 were recovered from Oregon cattle. One isolate was recovered from a 1-week-old calf with pneumoenteritis, and 1 isolate from an 8-month-old bull with fever and respiratory disease. Two isolates were recovered as latent viruses in testicular cell cultures. All 4 isolates of the virus were shown to have certain physical, chemical, biologic, and antigenic characteristics similar to previously described strains of bovine adenovirus type 4. Of 246 adult beef and dairy cattle in Oregon, 51% had serum-viral neutralizing antibodies to the type 4 virus at the 1:8 dilution level."}
{"id": "PMID:202180", "title": "Demonstration of equine infectious anemia virus in primary leukocyte cultures by electron microscopy.", "content": "Electron microscopy was used to demonstrate the presence of viral particles in primary cultures of leukocytes taken from a horse after SC inoculation with the Wyoming strain of equine infectious anemia virus. Unlike previous studies, the exposure virus was not passaged through cell culture prior to horse inoculation. Cultures were begun approximately 1 week before and 1 week after the 1st pyrexic period after inoculation. In both samples, viral particles and cytoplasmic alterations were observed resembling those previously reported in equine infectious anemia virus and other retravirus-infected cells.", "contents": "Demonstration of equine infectious anemia virus in primary leukocyte cultures by electron microscopy. Electron microscopy was used to demonstrate the presence of viral particles in primary cultures of leukocytes taken from a horse after SC inoculation with the Wyoming strain of equine infectious anemia virus. Unlike previous studies, the exposure virus was not passaged through cell culture prior to horse inoculation. Cultures were begun approximately 1 week before and 1 week after the 1st pyrexic period after inoculation. In both samples, viral particles and cytoplasmic alterations were observed resembling those previously reported in equine infectious anemia virus and other retravirus-infected cells."}
{"id": "PMID:202181", "title": "Prevalence of ovine progressive pneumonia in a sampling of cull sheep from western and midwestern United States.", "content": "Ovine progressive pneumonia was found to be prevalent in many major sheep-producing areas in the United States. The incidence was determined in a sampling of cull sheep (5 to 10 years of age) at slaughter. Diagnostic criteria were based on finding viral-specific immunoglobulins, virus, or lesions. Each method indicated a high incidence in samplings from midwestern and northwestern states and a relatively low incidence in the sampling from southwestern states. Of those sheep examined, precipitating immuno-globulin to the causal virus was seen in 1.0% to 67.5%, virus was isolated from the lungs of 0% to 46.2%, and lymphoid hyperplasia was seen in the lungs of 0% to 38.5%. The most common lesions in the lungs (from which virus was isolated) were multiple lymphoid nodules and increased fibromuscular tissue.", "contents": "Prevalence of ovine progressive pneumonia in a sampling of cull sheep from western and midwestern United States. Ovine progressive pneumonia was found to be prevalent in many major sheep-producing areas in the United States. The incidence was determined in a sampling of cull sheep (5 to 10 years of age) at slaughter. Diagnostic criteria were based on finding viral-specific immunoglobulins, virus, or lesions. Each method indicated a high incidence in samplings from midwestern and northwestern states and a relatively low incidence in the sampling from southwestern states. Of those sheep examined, precipitating immuno-globulin to the causal virus was seen in 1.0% to 67.5%, virus was isolated from the lungs of 0% to 46.2%, and lymphoid hyperplasia was seen in the lungs of 0% to 38.5%. The most common lesions in the lungs (from which virus was isolated) were multiple lymphoid nodules and increased fibromuscular tissue."}
{"id": "PMID:202183", "title": "Oropharyngeal excretion of Epstein-Barr virus by patients with lymphoproliferative disorders and by recipients of renal homografts.", "content": "In an attempt to associate oropharyngeal excretion of Epstein-Barr (EB) virus with lymphoproliferative disorders other than infectious mononucleosis, we tested throat gargles collected from adult subjects for the EB virus. Nine (16%) of 55 healthy persons were positive. High EB virus-excretion rates were found among patients with active acute lymphocytic leukemia (6/6, 100%), among renal homograft recipients during the third to 12th month after transplantation (26/30, 87%), and among critically ill patients with leukemia-lymphoma (14/19, 74%). Moderately high excretion rates were found among patients with myeloma (7/16, 44%), patients with poorly differentiated lymphocytic lymphoma (5/11, 44%), critically ill patients with solid cancers (15/37, 41%), and patients with chronic myelogenous leukemia (8/21, 38%). Our data suggested that the higher than normal excretion rate is realted to the basic disease process and to the general health status but not to the duration of cancer chemotherapy.", "contents": "Oropharyngeal excretion of Epstein-Barr virus by patients with lymphoproliferative disorders and by recipients of renal homografts. In an attempt to associate oropharyngeal excretion of Epstein-Barr (EB) virus with lymphoproliferative disorders other than infectious mononucleosis, we tested throat gargles collected from adult subjects for the EB virus. Nine (16%) of 55 healthy persons were positive. High EB virus-excretion rates were found among patients with active acute lymphocytic leukemia (6/6, 100%), among renal homograft recipients during the third to 12th month after transplantation (26/30, 87%), and among critically ill patients with leukemia-lymphoma (14/19, 74%). Moderately high excretion rates were found among patients with myeloma (7/16, 44%), patients with poorly differentiated lymphocytic lymphoma (5/11, 44%), critically ill patients with solid cancers (15/37, 41%), and patients with chronic myelogenous leukemia (8/21, 38%). Our data suggested that the higher than normal excretion rate is realted to the basic disease process and to the general health status but not to the duration of cancer chemotherapy."}
{"id": "PMID:202186", "title": "[Corticosteroids determination in pig plasma (author's transl)].", "content": "To measure corticosteroid levels in peripheral blood of pig, the competitive protein-binding assay of Murphy was compared to a fluorimetric determination of cortisol and corticosterone previously separated by thin-layer chromatography. Accuracy and precision of each technique were determined. Concentration of corticosteroids were found to be 3.4 +/- 0.3 microgram/100 ml by competitive protein-binding and 2.4 +/- 0.2 microgram cortisol/100 ml and 0.3 +/- 0.03 microgram corticosterone/100 ml by fluorimetric determination. These levels were subject to diurnal variations. They were increased by ACTH administration and decreased by dexamethasone treatment. Both techniques were found to be sensitive and accurate to assess adrenal function in pigs. The competitive protein-binding assay, in spite of its relative lack of specificity, would appear to be suitable for routine analysis.", "contents": "[Corticosteroids determination in pig plasma (author's transl)]. To measure corticosteroid levels in peripheral blood of pig, the competitive protein-binding assay of Murphy was compared to a fluorimetric determination of cortisol and corticosterone previously separated by thin-layer chromatography. Accuracy and precision of each technique were determined. Concentration of corticosteroids were found to be 3.4 +/- 0.3 microgram/100 ml by competitive protein-binding and 2.4 +/- 0.2 microgram cortisol/100 ml and 0.3 +/- 0.03 microgram corticosterone/100 ml by fluorimetric determination. These levels were subject to diurnal variations. They were increased by ACTH administration and decreased by dexamethasone treatment. Both techniques were found to be sensitive and accurate to assess adrenal function in pigs. The competitive protein-binding assay, in spite of its relative lack of specificity, would appear to be suitable for routine analysis."}
{"id": "PMID:202185", "title": "Early x-ray diagnosis of occult infiltrating nasopharyngeal carcinoma.", "content": "The occult type of nasopharyngeal carcinoma (NPC) accounts for 30% of all nasopharyngeal carcinomas. The occult NPC is clinically difficult to visualize, because the tumor infiltrates and grows in the submucosa. It then metastasizes to the skull base or draining lymph nodes. When the NPC is finally diagnosed, the prognosis is poor. Three refined x-ray techniques are evaluated for their utilization in earlier diagnosis of the occult NPC: thin section tomography, nasopharyngography, and Eustachian tube function studies. In a consecutive series of 50 patients, these techniques detected 12 infiltrating carcinomas not visible on clinical examination. Five of these patients also had initially negative blind biopsies. Patients having diplopia, facial numbness, cervical adenopathy, and chronic serous otitis media are highly suspect for NPC. The described x-ray techniques, that are safe and noninvasive, can detect these occult infiltrative tumors earlier than clinical examination. Earlier detection and treatment of NPC has resulted in a significant increased cure rate.", "contents": "Early x-ray diagnosis of occult infiltrating nasopharyngeal carcinoma. The occult type of nasopharyngeal carcinoma (NPC) accounts for 30% of all nasopharyngeal carcinomas. The occult NPC is clinically difficult to visualize, because the tumor infiltrates and grows in the submucosa. It then metastasizes to the skull base or draining lymph nodes. When the NPC is finally diagnosed, the prognosis is poor. Three refined x-ray techniques are evaluated for their utilization in earlier diagnosis of the occult NPC: thin section tomography, nasopharyngography, and Eustachian tube function studies. In a consecutive series of 50 patients, these techniques detected 12 infiltrating carcinomas not visible on clinical examination. Five of these patients also had initially negative blind biopsies. Patients having diplopia, facial numbness, cervical adenopathy, and chronic serous otitis media are highly suspect for NPC. The described x-ray techniques, that are safe and noninvasive, can detect these occult infiltrative tumors earlier than clinical examination. Earlier detection and treatment of NPC has resulted in a significant increased cure rate."}
{"id": "PMID:202191", "title": "[Antiviral properties of analogs of distamycin A].", "content": "The effect of 9 analogues of distamycin A was studied in a tissue culture with respect to the virus of a smallpox vaccine and classical avian plague. Three analogues of distamycin A (I, VI, VII) were studied in chick embryos with respect to the smallpox and influenza viruses. The analogues were characterized by a loss or decrease of the activity against the smallpox vaccine virus as compared to distamycin A. In contrast to distamycin A analogue VII had an inhibitory effect on influenza infection in chick embryos.", "contents": "[Antiviral properties of analogs of distamycin A]. The effect of 9 analogues of distamycin A was studied in a tissue culture with respect to the virus of a smallpox vaccine and classical avian plague. Three analogues of distamycin A (I, VI, VII) were studied in chick embryos with respect to the smallpox and influenza viruses. The analogues were characterized by a loss or decrease of the activity against the smallpox vaccine virus as compared to distamycin A. In contrast to distamycin A analogue VII had an inhibitory effect on influenza infection in chick embryos."}
{"id": "PMID:202192", "title": "ATP formation associated with fumarate and nitrate reduction in growing cultures of Veillonella alcalescens.", "content": "Molar growth yields, fermentation balances and enzyme activities were measured in Veillonella alcalescens grown anaerobically with different substrates in the absence or presence of fumarate or nitrate. The molar growth yields on malate (14.3 g dry wt bacteria/mole substrate) and citrate (19.3) were higher than that on lactate (8.6). The molar growth yield on lactate was increased to 15.5 or 19.8 by the addition of fumarate or nitrate, respectively, to the growth medium, and the molar growth yield on citrate was increased to 25.3 by addition of nitrate. Active growth on pyruvate was only observed in the presence of nitrate, and the molar growth yield was 25.5. From fermentation balances and fermentation systems similar YATP values (g dry wt bacteria/mole ATP) were calculated for all substrates or mixtures of substrates assuming that one mole of ATP is generated at the electron transport from pyruvate, NADH and NADPH to nitrate or fumarate whereas ATP is not produced in the electron transport from lactate to fumarate or nitrate, and, therefore, this assumption was considered to reflect the actual situation. The mean YATP value at a doubling time of 1 h was 16.5 g dry wt bacteria/mole ATP for growth without an added hydrogen acceptor, 14.4 for growth with fumarate, and 14.2 for growth with nitrate.", "contents": "ATP formation associated with fumarate and nitrate reduction in growing cultures of Veillonella alcalescens. Molar growth yields, fermentation balances and enzyme activities were measured in Veillonella alcalescens grown anaerobically with different substrates in the absence or presence of fumarate or nitrate. The molar growth yields on malate (14.3 g dry wt bacteria/mole substrate) and citrate (19.3) were higher than that on lactate (8.6). The molar growth yield on lactate was increased to 15.5 or 19.8 by the addition of fumarate or nitrate, respectively, to the growth medium, and the molar growth yield on citrate was increased to 25.3 by addition of nitrate. Active growth on pyruvate was only observed in the presence of nitrate, and the molar growth yield was 25.5. From fermentation balances and fermentation systems similar YATP values (g dry wt bacteria/mole ATP) were calculated for all substrates or mixtures of substrates assuming that one mole of ATP is generated at the electron transport from pyruvate, NADH and NADPH to nitrate or fumarate whereas ATP is not produced in the electron transport from lactate to fumarate or nitrate, and, therefore, this assumption was considered to reflect the actual situation. The mean YATP value at a doubling time of 1 h was 16.5 g dry wt bacteria/mole ATP for growth without an added hydrogen acceptor, 14.4 for growth with fumarate, and 14.2 for growth with nitrate."}
{"id": "PMID:202193", "title": "Virus production with a newly developed microcarrier system.", "content": "Primary cell cultures as well as established lines have been grown on a recently developed microcarrier configuration that overcomes the problem of toxicity attendant on earlier developments in this technology. Virus yields from these cells propagated on the new microcarriers have been measured. Microcarrier-grown cells, when compared to roller-bottle-grown cells, gave virus yields on a per-cell basis that varied from slightly greater with the Sindbis virus-Chinese hamster ovary cells and polio-WI-38 combinations to approximately one-third with Moloney murine leukemia virus-Cl-1 mouse cells and vesicular stomatitis virus-chicken embryo fibroblasts. Yields ranged from 8.0 X 10(7) to 3.6 X 10(8) cells per 100-ml microcarrier culture and from 3.7 X 10(7) to 4.1 X 20(8) cells per roller-bottle culture. Secondary chicken embryo fibroblast yields were approximately four times as great in microcarrier cultures as in standard roller-bottle cultures, per unit volume of medium consumed. In spite of the reduced virus yields per cell seen in some instances, the greater cellular productivity of microcarrier cultures appears to hold great promise for large-scale virus production. Optimizing microcarrier conditions for specific cell-virus systems should result in improved yields.", "contents": "Virus production with a newly developed microcarrier system. Primary cell cultures as well as established lines have been grown on a recently developed microcarrier configuration that overcomes the problem of toxicity attendant on earlier developments in this technology. Virus yields from these cells propagated on the new microcarriers have been measured. Microcarrier-grown cells, when compared to roller-bottle-grown cells, gave virus yields on a per-cell basis that varied from slightly greater with the Sindbis virus-Chinese hamster ovary cells and polio-WI-38 combinations to approximately one-third with Moloney murine leukemia virus-Cl-1 mouse cells and vesicular stomatitis virus-chicken embryo fibroblasts. Yields ranged from 8.0 X 10(7) to 3.6 X 10(8) cells per 100-ml microcarrier culture and from 3.7 X 10(7) to 4.1 X 20(8) cells per roller-bottle culture. Secondary chicken embryo fibroblast yields were approximately four times as great in microcarrier cultures as in standard roller-bottle cultures, per unit volume of medium consumed. In spite of the reduced virus yields per cell seen in some instances, the greater cellular productivity of microcarrier cultures appears to hold great promise for large-scale virus production. Optimizing microcarrier conditions for specific cell-virus systems should result in improved yields."}
{"id": "PMID:202194", "title": "Increase in arginine and citrulline production by 6-azauracil-resistant mutants of Bacillus subtilis.", "content": "In the arginine producer AHr-5, an L-arginine hydroxamate-resistant mutant of Bacillus subtilis, accumulation of N8-acetyl-L-ornithine increased as the level of L-arginine accumulation increased in the medium containing L-glutamic acid. Ornithine carbamoyltransferase of this strain was genetically derepressed. These results suggested that carbamoylphosphate might be deficient in vivo. With the intention to increase endogenous carbamoylphosphate, pyrimidine analogs inhibiting growth were selected and the mutants resistant to these compounds were derived from the AHr-5 mutant. Of the resistant mutants derived, the 6-azauracil-resistant mutant AAr-9 produced 28 mg of L-arginine per ml, which corresponded to more than twofold the amount produced by the parent strain. Derivation of an arginine-requiring mutant from the double-resistant mutant AAr-9 provides a new advantageous method for the production of L-citrulline. The increase in arginine and citrulline production is discussed.", "contents": "Increase in arginine and citrulline production by 6-azauracil-resistant mutants of Bacillus subtilis. In the arginine producer AHr-5, an L-arginine hydroxamate-resistant mutant of Bacillus subtilis, accumulation of N8-acetyl-L-ornithine increased as the level of L-arginine accumulation increased in the medium containing L-glutamic acid. Ornithine carbamoyltransferase of this strain was genetically derepressed. These results suggested that carbamoylphosphate might be deficient in vivo. With the intention to increase endogenous carbamoylphosphate, pyrimidine analogs inhibiting growth were selected and the mutants resistant to these compounds were derived from the AHr-5 mutant. Of the resistant mutants derived, the 6-azauracil-resistant mutant AAr-9 produced 28 mg of L-arginine per ml, which corresponded to more than twofold the amount produced by the parent strain. Derivation of an arginine-requiring mutant from the double-resistant mutant AAr-9 provides a new advantageous method for the production of L-citrulline. The increase in arginine and citrulline production is discussed."}
{"id": "PMID:202195", "title": "Development of poliovirus having increased resistance to chlorine inactivation.", "content": "A laboratory strain of poliovirus (LSc) became progressively more resistant to chlorine inactivation during a series of repeated sublethal exposures to the halogen.", "contents": "Development of poliovirus having increased resistance to chlorine inactivation. A laboratory strain of poliovirus (LSc) became progressively more resistant to chlorine inactivation during a series of repeated sublethal exposures to the halogen."}
{"id": "PMID:202203", "title": "Ultrastructure of cutaneous cellular infiltrates in scleroderma.", "content": "Electron microscopy of the skin was performed in ten patients with systemic and four with localized scleroderma. The following three groups of cells were identified: (1) mature lymphocytes, T lymphoblasts, immature plasma cells, and plasma cells; (2) fibroblasts, fibrocytes, and fibroblast-like cells; and (3) macrophages, undifferentiated mesenchymal cells, and monocytes. Inthose specimens with mononuclear cell infiltrates, the most common cells were lymphocytic-types, macrophages, and fibroblasts with well developed rough endoplasmic reticulum. In the specimens at the fibrotic stage, fibroblasts and histiocytic-type cells predominated. This study suggests that cellular and humoral immunity may play a role in the pathophysiology of scleroderma.", "contents": "Ultrastructure of cutaneous cellular infiltrates in scleroderma. Electron microscopy of the skin was performed in ten patients with systemic and four with localized scleroderma. The following three groups of cells were identified: (1) mature lymphocytes, T lymphoblasts, immature plasma cells, and plasma cells; (2) fibroblasts, fibrocytes, and fibroblast-like cells; and (3) macrophages, undifferentiated mesenchymal cells, and monocytes. Inthose specimens with mononuclear cell infiltrates, the most common cells were lymphocytic-types, macrophages, and fibroblasts with well developed rough endoplasmic reticulum. In the specimens at the fibrotic stage, fibroblasts and histiocytic-type cells predominated. This study suggests that cellular and humoral immunity may play a role in the pathophysiology of scleroderma."}
{"id": "PMID:202204", "title": "[The neural periphery in lichen planus lesions (author's transl)].", "content": "In 12 patients suffering from generalized Lichen planus (L.p.) the neural periphery of lesions was studied by modern histochemical and electron microscopical methods. In contrast to the investigations published until now on this subject no signs of neural hyperplasia in L.p. could be found. Only some nerves localized in the Lichen planus infiltrate exhibited morphological changes indicating increased neural de- and regeneration in this region. According to the results obtained the nerve changes in L.p. are caused by the typical inflammatory reaction found in this dermatosis. Therefore the neural theory of L.p. cannot be sustained on a histological basis.", "contents": "[The neural periphery in lichen planus lesions (author's transl)]. In 12 patients suffering from generalized Lichen planus (L.p.) the neural periphery of lesions was studied by modern histochemical and electron microscopical methods. In contrast to the investigations published until now on this subject no signs of neural hyperplasia in L.p. could be found. Only some nerves localized in the Lichen planus infiltrate exhibited morphological changes indicating increased neural de- and regeneration in this region. According to the results obtained the nerve changes in L.p. are caused by the typical inflammatory reaction found in this dermatosis. Therefore the neural theory of L.p. cannot be sustained on a histological basis."}
{"id": "PMID:202205", "title": "Does adrenergic activity suppress insulin secretion during surgery? A clinical experiment with halothane anesthesia.", "content": "Peroperative inhibition of insulin release is widely attributed to increased alpha-adrenergic activity. To test this hypothesis serum insulin and glucose concentrations were measured at short intervals in 11 patients who underwent major surgery. Five patients were anesthetized with halothane and six with general anesthesia without halothane. The results were similar in both patient groups; halothane had no effect on insulin. This suggests that suppression of insulin under operations is probably not due to activation of the alpha-adrenergic receptors of the pancreatic beta-cells. The authors propose that suppression of insulin secretion during surgery may be caused by adrenaline, which, in competing for the glucose receptors, insensitizes the pancreatic beta-cells.", "contents": "Does adrenergic activity suppress insulin secretion during surgery? A clinical experiment with halothane anesthesia. Peroperative inhibition of insulin release is widely attributed to increased alpha-adrenergic activity. To test this hypothesis serum insulin and glucose concentrations were measured at short intervals in 11 patients who underwent major surgery. Five patients were anesthetized with halothane and six with general anesthesia without halothane. The results were similar in both patient groups; halothane had no effect on insulin. This suggests that suppression of insulin under operations is probably not due to activation of the alpha-adrenergic receptors of the pancreatic beta-cells. The authors propose that suppression of insulin secretion during surgery may be caused by adrenaline, which, in competing for the glucose receptors, insensitizes the pancreatic beta-cells."}
{"id": "PMID:202207", "title": "The importance of mediastinal lymph node invasion by pulmonary carcinoma in selection of patients for resection.", "content": "Resection results from 417 consecutive patients operated on between January 1, 1964, and December 30, 1969, were analyzed in March, 1976. This period was chosen to allow a five-year follow-up. The results of resection in 56 patients with invaded mediastinal nodes are reported. Mediastinoscopy to assess resectability was not used for any of the 417 patients. Our low incidence of mediastinal node invasion (56 out of 417, or 13.4%), a resectability rate of 97.4%, and a hospital mortality of 2.8% for resection of advanced carcinoma suggest that routine mediastinoscopy prior to resection is not necessary. Traditional methods of preoperative assessment and the use, when indicated, of extended resection for patients with mediastinal node invasion result in worthwhile salvage of patients with invaded mediastinal nodes.", "contents": "The importance of mediastinal lymph node invasion by pulmonary carcinoma in selection of patients for resection. Resection results from 417 consecutive patients operated on between January 1, 1964, and December 30, 1969, were analyzed in March, 1976. This period was chosen to allow a five-year follow-up. The results of resection in 56 patients with invaded mediastinal nodes are reported. Mediastinoscopy to assess resectability was not used for any of the 417 patients. Our low incidence of mediastinal node invasion (56 out of 417, or 13.4%), a resectability rate of 97.4%, and a hospital mortality of 2.8% for resection of advanced carcinoma suggest that routine mediastinoscopy prior to resection is not necessary. Traditional methods of preoperative assessment and the use, when indicated, of extended resection for patients with mediastinal node invasion result in worthwhile salvage of patients with invaded mediastinal nodes."}
{"id": "PMID:202208", "title": "Primary amyloidosis with familial vitreous opacities: an unusual case and family.", "content": "Peripheral neuropathy was not found even six to ten years after the onset of visual symptoms in a family with primary amyloidosis, except in the propositus at the terminal stage. The propositus had mainly ocular and CNS involvement. An ocular manifestation, the vitreous opacity, was the only involvement in the family members, in spite of the long clinical course. This family may have a different type of familial primary amyloidosis from that previously reported.", "contents": "Primary amyloidosis with familial vitreous opacities: an unusual case and family. Peripheral neuropathy was not found even six to ten years after the onset of visual symptoms in a family with primary amyloidosis, except in the propositus at the terminal stage. The propositus had mainly ocular and CNS involvement. An ocular manifestation, the vitreous opacity, was the only involvement in the family members, in spite of the long clinical course. This family may have a different type of familial primary amyloidosis from that previously reported."}
{"id": "PMID:202211", "title": "Effect of dibutyryl cyclic adenosine monophosphate on active amino acid transport in Streptomyces hydrogenans.", "content": "The active uptake of 2-aminoisobutyric acid (AIB) and several other amino acids in resting cells of Streptomyces hydrogenans was found to be stimulated by exogenously added adenosine cyclic monophosphate (cAMP). The uptake of glycerol, sorbose, and pyrimidine nucleosides remained unaffected. Among the various cAMP derivatives tested, the dibutyryl derivative was found to be most effective, followed by monobutyryl cAMP, and cAMP. Dibutyryl cGMP was also found to stimulate AIB transport, and its effectivity was as good as that of dibutyryl cAMP. The effect of dibutyryl cAMP is time dependent and attains its maximum after 40--60 min of incubation at 30 degrees C in K-Na-phosphate buffer. Dibutyryl cAMP-dependent transport stimulation has a high temperature coefficient and is prevented by rifamycin SV or chloramphenicol. The rate of leucine incorporation into protein was rapidly increased upon addition of dibutyryl cAMP. Kinetic studies reveal that the stimulation of AIB transport is characterized by an increase in maximum uptake rate and an unaltered apparent Michaelis constant. Analysis of the unidirectional fluxes show that both influx and efflux are enhanced by dibutyryl cAMP. It is concluded that exogenous dibutyryl cAMP stimulates de novo synthesis of certain proteins including the transport catalysts for various amino acids.", "contents": "Effect of dibutyryl cyclic adenosine monophosphate on active amino acid transport in Streptomyces hydrogenans. The active uptake of 2-aminoisobutyric acid (AIB) and several other amino acids in resting cells of Streptomyces hydrogenans was found to be stimulated by exogenously added adenosine cyclic monophosphate (cAMP). The uptake of glycerol, sorbose, and pyrimidine nucleosides remained unaffected. Among the various cAMP derivatives tested, the dibutyryl derivative was found to be most effective, followed by monobutyryl cAMP, and cAMP. Dibutyryl cGMP was also found to stimulate AIB transport, and its effectivity was as good as that of dibutyryl cAMP. The effect of dibutyryl cAMP is time dependent and attains its maximum after 40--60 min of incubation at 30 degrees C in K-Na-phosphate buffer. Dibutyryl cAMP-dependent transport stimulation has a high temperature coefficient and is prevented by rifamycin SV or chloramphenicol. The rate of leucine incorporation into protein was rapidly increased upon addition of dibutyryl cAMP. Kinetic studies reveal that the stimulation of AIB transport is characterized by an increase in maximum uptake rate and an unaltered apparent Michaelis constant. Analysis of the unidirectional fluxes show that both influx and efflux are enhanced by dibutyryl cAMP. It is concluded that exogenous dibutyryl cAMP stimulates de novo synthesis of certain proteins including the transport catalysts for various amino acids."}
{"id": "PMID:202212", "title": "Active transport of oxalate by Pseudomonas oxalaticus OX1.", "content": "Membrane vesicles isolated from oxalate-grown cells of Pseudomonas oxalaticus accumulated oxalate by an inducible transport system in unmodified form against a concentration gradient. This accumulation was dependent on the presence of a suitable electron donor system such as ascorbate-phenazine-methosulphate. In the presence of this energy source, steady state levels of accumulation of oxalate were 10--20-fold higher than in its absence. The oxalate transport system involved showed a high affinity for oxalate (Km = 11 micron) and was highly specific. Oxalate transport was not affected by the presence of other dicarboxylic acids, such as malate, succinate and fumarate and only partly inhibited by acetate. The energy requirement for oxalate transport is discussed and it is concluded that this requirement is most likely equivalent to 1 mole of ATP per mole of oxalate.", "contents": "Active transport of oxalate by Pseudomonas oxalaticus OX1. Membrane vesicles isolated from oxalate-grown cells of Pseudomonas oxalaticus accumulated oxalate by an inducible transport system in unmodified form against a concentration gradient. This accumulation was dependent on the presence of a suitable electron donor system such as ascorbate-phenazine-methosulphate. In the presence of this energy source, steady state levels of accumulation of oxalate were 10--20-fold higher than in its absence. The oxalate transport system involved showed a high affinity for oxalate (Km = 11 micron) and was highly specific. Oxalate transport was not affected by the presence of other dicarboxylic acids, such as malate, succinate and fumarate and only partly inhibited by acetate. The energy requirement for oxalate transport is discussed and it is concluded that this requirement is most likely equivalent to 1 mole of ATP per mole of oxalate."}
{"id": "PMID:202213", "title": "Interferon induction by double-stranded like complexes of vinyl copolymers with polynucleotides.", "content": "Interferon-inducing capacity of polyvinyl nucleobases paired with polyribonucleotides was examined. We confirmed the data showing that vinyl copolymers could provide structural analogues of polyribonucleotides being effective in interferon induction.", "contents": "Interferon induction by double-stranded like complexes of vinyl copolymers with polynucleotides. Interferon-inducing capacity of polyvinyl nucleobases paired with polyribonucleotides was examined. We confirmed the data showing that vinyl copolymers could provide structural analogues of polyribonucleotides being effective in interferon induction."}
{"id": "PMID:202214", "title": "Psychopharmaca and electroconvulsive therapy in relation to viral antibodies and interferon. Experimental and clinical study.", "content": "Chlorpromazine (CHP) in a concentration of 8.3 microgram per ml medium inhibited attachment and multiplication of CEC and of various cell lines. The same CHP concentration applied to grown CEC monolayers inhibited the growth of TBEV but not the growth of HHV 1, while interferon was slightly stimulated. The clinical course of fatal subcutaneous TBEV infection in mice was not affected by daily CHP treatment while brain and serum interferon were stimulated. Antibody formation in TBEV infected or HHV 1 immunized mice was not affected significantly by CHP application. The following data were obtained in a longitudinal study on 28 hospitalized schizophrenic patients: 89 percent of them revealed at least some serological findings which indicate an actual HHV 1 infectious process-elevated NAB titers, high ratio between complement requiring and complement not requiring NAB titers. A low interferon activity was observed in serum and cerebrospinal fluid of 93 percent and 14 percent patients, respectively. No regular correlation between HHV 1-NAB-both complement requiring and complement not requiring-and of interferon on one side and between hospitalization. CHP treatment and electroconvulsive therapy on the other side has been observed.", "contents": "Psychopharmaca and electroconvulsive therapy in relation to viral antibodies and interferon. Experimental and clinical study. Chlorpromazine (CHP) in a concentration of 8.3 microgram per ml medium inhibited attachment and multiplication of CEC and of various cell lines. The same CHP concentration applied to grown CEC monolayers inhibited the growth of TBEV but not the growth of HHV 1, while interferon was slightly stimulated. The clinical course of fatal subcutaneous TBEV infection in mice was not affected by daily CHP treatment while brain and serum interferon were stimulated. Antibody formation in TBEV infected or HHV 1 immunized mice was not affected significantly by CHP application. The following data were obtained in a longitudinal study on 28 hospitalized schizophrenic patients: 89 percent of them revealed at least some serological findings which indicate an actual HHV 1 infectious process-elevated NAB titers, high ratio between complement requiring and complement not requiring NAB titers. A low interferon activity was observed in serum and cerebrospinal fluid of 93 percent and 14 percent patients, respectively. No regular correlation between HHV 1-NAB-both complement requiring and complement not requiring-and of interferon on one side and between hospitalization. CHP treatment and electroconvulsive therapy on the other side has been observed."}
{"id": "PMID:202215", "title": "Effect of impulsin treatment of interferon production and antiviral resistance of mice.", "content": "The effect of N-(2-hydroxyethyl)-palmitamide (Impulsin, Spofa)--an active endogenous compound which is recommended for preventing virus infection of the respiratory tract--on interferon production in mice stimulated with double stranded RNA and on the course of disease caused by encephalomyocarditis virus (EMC) was studied. Impulsin itself did not stimulate interferon production in mice treated per os or intravenously. But repeated application of this drug per os induced a macrophage activation, reflected by enhanced interferon production in vitro. When the interferon stimulation was delayed until 4 to 10 days after the first dose of Impulsin, interferon response to ds-RNA was slightly increased. After this phase of enhanced activity a decreased production of interferon was observed. Impulsin was not significantly effective in protecting mice from lethal dose of EMC virus. Application of this drug had an inhibitory effect on the toxicity of ds-RNA. A possible explanation of the mechanism by which Impulsin decreased the toxicity of virus in the organism is discussed.", "contents": "Effect of impulsin treatment of interferon production and antiviral resistance of mice. The effect of N-(2-hydroxyethyl)-palmitamide (Impulsin, Spofa)--an active endogenous compound which is recommended for preventing virus infection of the respiratory tract--on interferon production in mice stimulated with double stranded RNA and on the course of disease caused by encephalomyocarditis virus (EMC) was studied. Impulsin itself did not stimulate interferon production in mice treated per os or intravenously. But repeated application of this drug per os induced a macrophage activation, reflected by enhanced interferon production in vitro. When the interferon stimulation was delayed until 4 to 10 days after the first dose of Impulsin, interferon response to ds-RNA was slightly increased. After this phase of enhanced activity a decreased production of interferon was observed. Impulsin was not significantly effective in protecting mice from lethal dose of EMC virus. Application of this drug had an inhibitory effect on the toxicity of ds-RNA. A possible explanation of the mechanism by which Impulsin decreased the toxicity of virus in the organism is discussed."}
{"id": "PMID:202216", "title": "Physicochemical characteristics of IME-inhibitor of interferon activity from mouse embryo tissues.", "content": "Further investigation with the inhibitor of interferon activity (IME) isolated from mouse embryo tissue is reported. The present results bring some new data concerning the physiochemical properties of the interferon antagonist. It is not dialysable, not sensitive to trypsin, lysozyme, hyaluronidase, RNAse and pH 2, but is sensitive to pH 10 and neuraminidase. Concentrated and partly purified tissue antagonist of interferon was separated on a column with Sephadex G 100. Three distinct, well separated fractions showing antiinterferon activity were obtained. The characteristics and molecular weight of each of these fractions were determined.", "contents": "Physicochemical characteristics of IME-inhibitor of interferon activity from mouse embryo tissues. Further investigation with the inhibitor of interferon activity (IME) isolated from mouse embryo tissue is reported. The present results bring some new data concerning the physiochemical properties of the interferon antagonist. It is not dialysable, not sensitive to trypsin, lysozyme, hyaluronidase, RNAse and pH 2, but is sensitive to pH 10 and neuraminidase. Concentrated and partly purified tissue antagonist of interferon was separated on a column with Sephadex G 100. Three distinct, well separated fractions showing antiinterferon activity were obtained. The characteristics and molecular weight of each of these fractions were determined."}
{"id": "PMID:202217", "title": "Nucleic acid as interferon inducer. Its antiviral and antitumor activity.", "content": "The results of the present study have demonstrated that dsRNA obtained in the system E. coli--bacteriophage is an interferon inducer and possesses antiviral and antitumoral activities.", "contents": "Nucleic acid as interferon inducer. Its antiviral and antitumor activity. The results of the present study have demonstrated that dsRNA obtained in the system E. coli--bacteriophage is an interferon inducer and possesses antiviral and antitumoral activities."}
{"id": "PMID:202218", "title": "The influence of immunization on the production of interferon in vivo and in vitro.", "content": "The present study was undertaken to compare the production of interferon by immunized mice in response to different viral inducers. Porton mice were immunized with NDV or A/Wr11/57 virus by injecting 6-week-old animals with virus on days 1, 7, and 14. The interferon response was investigated 3 weeks later. Compared with controls, the A-immunized mice after stimulation in vivo, produced more interferon when NDV was used as inducer. It was shown in sera as well as in washings of peritoneal cells. In experiments in vitro induction of interferon with NDV or A/Wr11/57 virus in macrophages of immunized mice resulted in significant rise in interferon levels. These results are in agreement with earlier investigation of others and support the role of immune recognition in the interferon response.", "contents": "The influence of immunization on the production of interferon in vivo and in vitro. The present study was undertaken to compare the production of interferon by immunized mice in response to different viral inducers. Porton mice were immunized with NDV or A/Wr11/57 virus by injecting 6-week-old animals with virus on days 1, 7, and 14. The interferon response was investigated 3 weeks later. Compared with controls, the A-immunized mice after stimulation in vivo, produced more interferon when NDV was used as inducer. It was shown in sera as well as in washings of peritoneal cells. In experiments in vitro induction of interferon with NDV or A/Wr11/57 virus in macrophages of immunized mice resulted in significant rise in interferon levels. These results are in agreement with earlier investigation of others and support the role of immune recognition in the interferon response."}
{"id": "PMID:202219", "title": "Dietary and serum lipids in the multifactorial etiology of atherosclerosis.", "content": "The incidence of severe atherosclerosis is ascribable to a multiplicity of risk factors, cardinal among which is the serum cholesterol concentration. The dietary fat content, the serum cholesterol level, and the incidence of atherosclerosis are clearly correlated in different countries and in population cohorts. Within a population, the serum cholesterol level is a major independent risk factor for premature atherosclerotic disease.", "contents": "Dietary and serum lipids in the multifactorial etiology of atherosclerosis. The incidence of severe atherosclerosis is ascribable to a multiplicity of risk factors, cardinal among which is the serum cholesterol concentration. The dietary fat content, the serum cholesterol level, and the incidence of atherosclerosis are clearly correlated in different countries and in population cohorts. Within a population, the serum cholesterol level is a major independent risk factor for premature atherosclerotic disease."}
{"id": "PMID:202222", "title": "New insights into cholesterol dynamics.", "content": "Kinetic aspects of cholesterol dynamics are described, with flux from the gut, to the liver, to the tissues, and back to the liver and gut, with a discussion of modifying mechanisms, synthesis, and transport. Overproduction of cholesterol, and bile acid and cholesterol malabsorption, are related to clinical problems.", "contents": "New insights into cholesterol dynamics. Kinetic aspects of cholesterol dynamics are described, with flux from the gut, to the liver, to the tissues, and back to the liver and gut, with a discussion of modifying mechanisms, synthesis, and transport. Overproduction of cholesterol, and bile acid and cholesterol malabsorption, are related to clinical problems."}
{"id": "PMID:202225", "title": "Enhancement by diethylamineothyl-dextran of the plaque-forming activity of foot-and-mouth disease virus-antibody complexes in pig kidney IB-RS-2 cells.", "content": "Mixtures of foot-and-mouth disease (FMD) virus and homologous antibody, assayed for surviving plaque-forming units (PFU) in pig kidney IB-RS-2 cells, demonstrated an average ten-fold greater recovery of infectivity when diethylaminoethyl-dextran (DEAE-dextran) was included in the overlay medium. This enhancement, which was not detected in baby hamster kidney BHK21 cells, was due to the ability of the polycation to potentiate attachment of virus-antibody complexes to the IB-RS-2 cells. In some instances the effect was so pronounced that the plaque-forming activity of virus in the presence of homologous antibody exceeded that of virus alone.", "contents": "Enhancement by diethylamineothyl-dextran of the plaque-forming activity of foot-and-mouth disease virus-antibody complexes in pig kidney IB-RS-2 cells. Mixtures of foot-and-mouth disease (FMD) virus and homologous antibody, assayed for surviving plaque-forming units (PFU) in pig kidney IB-RS-2 cells, demonstrated an average ten-fold greater recovery of infectivity when diethylaminoethyl-dextran (DEAE-dextran) was included in the overlay medium. This enhancement, which was not detected in baby hamster kidney BHK21 cells, was due to the ability of the polycation to potentiate attachment of virus-antibody complexes to the IB-RS-2 cells. In some instances the effect was so pronounced that the plaque-forming activity of virus in the presence of homologous antibody exceeded that of virus alone."}
{"id": "PMID:202226", "title": "Rotavirus infection in lambs: pathogenesis and pathology.", "content": "Experimental lamb rotavirus infections were studied by immunofluorescence, histopathology and electron microscopy of tissues from infected gnotobiotic lambs killed at intervals from the incubation period to recovery. The rotavirus was demonstrated by immunofluorescence only in epithelial cells of villi in the small and large intestine, and virus antigen was most abundant during the incubation period. An increased enterocyte turnover rate was suggested by the rapid movement of virus-infected cells to the villus tip, and this increase may be one of the basic pathogenic mechanisms of rotavirus infection. Principal histopathological changes were shortening of villi and sloughing of epithelial cells. These were greatest in the middle and posterior small intestine at the onset of diarrhoea, but regeneration occurred within a few hours. Virus morphology in tissues was similar to that reported in other species, and virus presence correlated well with histopathological change.", "contents": "Rotavirus infection in lambs: pathogenesis and pathology. Experimental lamb rotavirus infections were studied by immunofluorescence, histopathology and electron microscopy of tissues from infected gnotobiotic lambs killed at intervals from the incubation period to recovery. The rotavirus was demonstrated by immunofluorescence only in epithelial cells of villi in the small and large intestine, and virus antigen was most abundant during the incubation period. An increased enterocyte turnover rate was suggested by the rapid movement of virus-infected cells to the villus tip, and this increase may be one of the basic pathogenic mechanisms of rotavirus infection. Principal histopathological changes were shortening of villi and sloughing of epithelial cells. These were greatest in the middle and posterior small intestine at the onset of diarrhoea, but regeneration occurred within a few hours. Virus morphology in tissues was similar to that reported in other species, and virus presence correlated well with histopathological change."}
{"id": "PMID:202227", "title": "Studies on glycopeptides of Herpes simplex virus infected cells.", "content": "Trypsinates from HSV infected cells, radioactively labeled with glucosamine and galactose were further digested by pronase. The digests were subjected to gel filtration, and it was shown that some of the eluted material consisted of saccharides, highly devoid of residual peptide. This material eluted between linear dextran markers of 19,000 and 3000 daltons. Only slight differences between uninfected and HSV infected cells in galactose and glucosamine derived radioactivity profiles of the chromatograms were detected. High molecular weight glucosamine labeled material, present in digest from uninfected cells, was not detectable in digests from HSV infected cells. The concanavalin A adsorbability of eluted fractions was tested. Changes in the relative adsorbability between materials from HSV and uninfected cells were present, especially for the glucosamine labeled saccharides.", "contents": "Studies on glycopeptides of Herpes simplex virus infected cells. Trypsinates from HSV infected cells, radioactively labeled with glucosamine and galactose were further digested by pronase. The digests were subjected to gel filtration, and it was shown that some of the eluted material consisted of saccharides, highly devoid of residual peptide. This material eluted between linear dextran markers of 19,000 and 3000 daltons. Only slight differences between uninfected and HSV infected cells in galactose and glucosamine derived radioactivity profiles of the chromatograms were detected. High molecular weight glucosamine labeled material, present in digest from uninfected cells, was not detectable in digests from HSV infected cells. The concanavalin A adsorbability of eluted fractions was tested. Changes in the relative adsorbability between materials from HSV and uninfected cells were present, especially for the glucosamine labeled saccharides."}
{"id": "PMID:202228", "title": "Murine cytomegalovirus infection in a non-permissive line of mouse fibroblasts.", "content": "A line of murine cytomegalovirus (MCMV)-resistant cells was derived from mouse embryo cultures. The virus penetrated the nuclei of these resistant cells efficiently and a small amount of viral gene transcription occurred, although no viral DNA synthesis was detected. Synthesis of cellular DNA, RNA and protein continued unabated, and the infected cells grew at the same rate as uninfected cells. The block in virus replication in these cells appears to be between early transcription and viral DNA synthesis.", "contents": "Murine cytomegalovirus infection in a non-permissive line of mouse fibroblasts. A line of murine cytomegalovirus (MCMV)-resistant cells was derived from mouse embryo cultures. The virus penetrated the nuclei of these resistant cells efficiently and a small amount of viral gene transcription occurred, although no viral DNA synthesis was detected. Synthesis of cellular DNA, RNA and protein continued unabated, and the infected cells grew at the same rate as uninfected cells. The block in virus replication in these cells appears to be between early transcription and viral DNA synthesis."}
{"id": "PMID:202229", "title": "Properties of Aleutian disease virus assayed with feline kidney cells.", "content": "Properties of Aleutian disease virus (ADV) were studied using feline kidney cells, line CRFK, to assay virus by the induction of nuclear antigen. ADV nuclear antigen was detected by immunofluorescent staining. Titers of virus obtained from mink spleens at 10-8 days after infection were usually between 10(3) and 10(5) infectious units per gram of spleen. ADV was purified by fluorocarbon extraction, differential centrifugation, biogel A-15 chromatography and CsCl equilibrium centrifugation. The molecular weight of the virus was estimated to be 3-5 X 10(5) daltons. The density of antigen-inducing virus in equilibrium CsCl gradients was 1.32--1.34 g/cm3. On velocity sucrose gradients, antigen-inducing virus had a sedimentation coefficient of approximately 110S. The virus was not neutralized by sera from chronically infected mink and ferrets and by sera from experimentally infected mink. ADV was resistant to ionic and nonionic detergents and lipid solvents. The titer of partially purified virus was reduced as much as 700-fold by proteolytic enzymes but not by DNase or RNase. The virus was inactivated slowly at 56 degrees C; the initial half-life was 90 minutes. It is concluded that the properties of ADV can be determined by assay in CRFK cells, thus facilitating virological study of the disease.", "contents": "Properties of Aleutian disease virus assayed with feline kidney cells. Properties of Aleutian disease virus (ADV) were studied using feline kidney cells, line CRFK, to assay virus by the induction of nuclear antigen. ADV nuclear antigen was detected by immunofluorescent staining. Titers of virus obtained from mink spleens at 10-8 days after infection were usually between 10(3) and 10(5) infectious units per gram of spleen. ADV was purified by fluorocarbon extraction, differential centrifugation, biogel A-15 chromatography and CsCl equilibrium centrifugation. The molecular weight of the virus was estimated to be 3-5 X 10(5) daltons. The density of antigen-inducing virus in equilibrium CsCl gradients was 1.32--1.34 g/cm3. On velocity sucrose gradients, antigen-inducing virus had a sedimentation coefficient of approximately 110S. The virus was not neutralized by sera from chronically infected mink and ferrets and by sera from experimentally infected mink. ADV was resistant to ionic and nonionic detergents and lipid solvents. The titer of partially purified virus was reduced as much as 700-fold by proteolytic enzymes but not by DNase or RNase. The virus was inactivated slowly at 56 degrees C; the initial half-life was 90 minutes. It is concluded that the properties of ADV can be determined by assay in CRFK cells, thus facilitating virological study of the disease."}
{"id": "PMID:202230", "title": "Electron microscopic studies on equine infectious anemia virus (EIAV). Brief report.", "content": "Morphological studies of EIAV reveal knobs on the surface of the particles, conically and tubularly shaped cores, budding particles with dense crescents directly underlying the plasma membrane, and distinct intracytoplasmic structures in infected cells.", "contents": "Electron microscopic studies on equine infectious anemia virus (EIAV). Brief report. Morphological studies of EIAV reveal knobs on the surface of the particles, conically and tubularly shaped cores, budding particles with dense crescents directly underlying the plasma membrane, and distinct intracytoplasmic structures in infected cells."}
{"id": "PMID:202232", "title": "[Cytochemical study of various enzymes of the rabbit crystalline lens epithelium].", "content": "The activity of a number of enzymes of glycolysis, tricarbonic acids, cycle, pentose phosphatase shunt and some important hydrolases, acid nucleases and adenosine triphosphate among them, was cytochemically determined in the rabbit lens epithelium. The data obtained clearly demonstrate the role the epithelium plays in energy producing processes of the lens, which are connected both with anaerobic and aerobic phases of glucose utilization and its direct oxydation, as well as with synthesis of some substances, with the transport of organic and inorganic molecules.", "contents": "[Cytochemical study of various enzymes of the rabbit crystalline lens epithelium]. The activity of a number of enzymes of glycolysis, tricarbonic acids, cycle, pentose phosphatase shunt and some important hydrolases, acid nucleases and adenosine triphosphate among them, was cytochemically determined in the rabbit lens epithelium. The data obtained clearly demonstrate the role the epithelium plays in energy producing processes of the lens, which are connected both with anaerobic and aerobic phases of glucose utilization and its direct oxydation, as well as with synthesis of some substances, with the transport of organic and inorganic molecules."}
{"id": "PMID:202235", "title": "Peripheral polyneuropathy associated with primary malignant lymphoma of the brain.", "content": "A patient with a primary malignant lymphoma of the brain manifested a peripheral polyneuropathy during his illness that could not be accounted for by the usual causes. The polyneuropathy is considered to be a nonmetastatic complication of the primary brain tumor. A review of the literature did not uncover a similar case.", "contents": "Peripheral polyneuropathy associated with primary malignant lymphoma of the brain. A patient with a primary malignant lymphoma of the brain manifested a peripheral polyneuropathy during his illness that could not be accounted for by the usual causes. The polyneuropathy is considered to be a nonmetastatic complication of the primary brain tumor. A review of the literature did not uncover a similar case."}
{"id": "PMID:202236", "title": "Corticosteroids in the treatment of Sydenham's chorea.", "content": "This is a retrospective study of the treatment of eight female patients with Sydenham's chorea by corticosteroid administration. The rationale for use of this medication is based on the concept that Sydenham's chorea is caused by an indolent inflammation of the small vessels in the caudate-putamen complex. All patients in this series responded to corticosteroid treatment relatively rapidly, with considerable diminution in abnormal movements. It is concluded that corticosteroid treatment of this condition is effective and deserves wider use. This report should serve as an impetus for more controlled studies.", "contents": "Corticosteroids in the treatment of Sydenham's chorea. This is a retrospective study of the treatment of eight female patients with Sydenham's chorea by corticosteroid administration. The rationale for use of this medication is based on the concept that Sydenham's chorea is caused by an indolent inflammation of the small vessels in the caudate-putamen complex. All patients in this series responded to corticosteroid treatment relatively rapidly, with considerable diminution in abnormal movements. It is concluded that corticosteroid treatment of this condition is effective and deserves wider use. This report should serve as an impetus for more controlled studies."}
{"id": "PMID:202245", "title": "Synthesis of haem and cytochrome c prosthetic group from delta-aminolaevulinate by the cell sap from rat liver.", "content": "To determine whether the prosthetic group of cytochrome c is synthesized and linked to the apoprotein in the cytosol or in connexion with the endoplasmic reticulum, we have studied the incorporation in vitro of delta-amino[(14)C]laevulinate into porphyrin compounds and cytochrome c by the cell sap from rat liver. The radioactive precursor was incorporated into a trichloroacetic acid-precipitable form partially resistant to extractions by acid solvents, suggesting the existence of a fraction covalently linked to protein. The activity was proportional to the amount of protein incubated, did not increase substantially by supplementation with the microsomal fraction and an energy source, and was very low in the pH5 fraction. Addition of increasing amounts of haemin inhibited the incorporation, as with purified delta-aminolaevulinate dehydratase. [(14)C]Protoporphyrin IX was identified by paper chromatography, together with a shoulder running as protohaem IX. The cell sap in the absence of ribosomes was also able to incorporate radioactivity into purified cytochrome c, and the addition of ribosomes significantly enhanced the activity. The precursors of haem c were synthesized in the soluble system by the known haem-synthetic pathway, as shown by the kinetics of labelling of the coproporphyrin, protoporphyrin and haem fractions, and the activities were concentrated in the precipitate obtained between 40 and 60% saturation with (NH(4))(2)SO(4). The presence of ferrochelatase was indicated by the incorporation of (55)Fe into proto- and haemato-haem identified by paper chromatography. It is concluded that the cell sap from rat liver contains the complete set of enzymes for the synthesis from delta-aminolaevulinate of haem c and its linkage to a small pool of free apoprotein c present in soluble form. This suggests that an ancillary pathway of haem synthesis occurs in the cytosol for at least the formation of the prosthetic group, which is linked post-translationally to that pool of apoprotein c synthesized by free polyribosomes.", "contents": "Synthesis of haem and cytochrome c prosthetic group from delta-aminolaevulinate by the cell sap from rat liver. To determine whether the prosthetic group of cytochrome c is synthesized and linked to the apoprotein in the cytosol or in connexion with the endoplasmic reticulum, we have studied the incorporation in vitro of delta-amino[(14)C]laevulinate into porphyrin compounds and cytochrome c by the cell sap from rat liver. The radioactive precursor was incorporated into a trichloroacetic acid-precipitable form partially resistant to extractions by acid solvents, suggesting the existence of a fraction covalently linked to protein. The activity was proportional to the amount of protein incubated, did not increase substantially by supplementation with the microsomal fraction and an energy source, and was very low in the pH5 fraction. Addition of increasing amounts of haemin inhibited the incorporation, as with purified delta-aminolaevulinate dehydratase. [(14)C]Protoporphyrin IX was identified by paper chromatography, together with a shoulder running as protohaem IX. The cell sap in the absence of ribosomes was also able to incorporate radioactivity into purified cytochrome c, and the addition of ribosomes significantly enhanced the activity. The precursors of haem c were synthesized in the soluble system by the known haem-synthetic pathway, as shown by the kinetics of labelling of the coproporphyrin, protoporphyrin and haem fractions, and the activities were concentrated in the precipitate obtained between 40 and 60% saturation with (NH(4))(2)SO(4). The presence of ferrochelatase was indicated by the incorporation of (55)Fe into proto- and haemato-haem identified by paper chromatography. It is concluded that the cell sap from rat liver contains the complete set of enzymes for the synthesis from delta-aminolaevulinate of haem c and its linkage to a small pool of free apoprotein c present in soluble form. This suggests that an ancillary pathway of haem synthesis occurs in the cytosol for at least the formation of the prosthetic group, which is linked post-translationally to that pool of apoprotein c synthesized by free polyribosomes."}
{"id": "PMID:202246", "title": "Changes in pulmonary surfactant and phosphatidylcholine metabolism in rats exposed to chrysotile asbestos dust.", "content": "1. Pulmonary surfactant was isolated from rats that had been exposed to chrysotile asbestos dust for from 3 days to 15 weeks. 2. Asbestos-treated rats showed a progressive increase in amounts of surfactant. After 15 weeks, treated animals contained 4 times as much as non-treated. 3. No significant change was seen in the total protein or total fatty acid composition of surfactant with exposure. 4. The increase in surfactant phosphatidylcholine normally seen on maturation of rat lung was accelerated by exposure of animals to asbestos. 5. An increase in the activity of phosphorylcholine glyceride transferase in lung homogenates and free cell populations was found. 6. Lysosomal phospholipase A was relatively unaffected by dust exposure. 7. It is suggested that the increase in surfactant amounts could be due to an increase in its synthesis without a corresponding alteration in its degradation.", "contents": "Changes in pulmonary surfactant and phosphatidylcholine metabolism in rats exposed to chrysotile asbestos dust. 1. Pulmonary surfactant was isolated from rats that had been exposed to chrysotile asbestos dust for from 3 days to 15 weeks. 2. Asbestos-treated rats showed a progressive increase in amounts of surfactant. After 15 weeks, treated animals contained 4 times as much as non-treated. 3. No significant change was seen in the total protein or total fatty acid composition of surfactant with exposure. 4. The increase in surfactant phosphatidylcholine normally seen on maturation of rat lung was accelerated by exposure of animals to asbestos. 5. An increase in the activity of phosphorylcholine glyceride transferase in lung homogenates and free cell populations was found. 6. Lysosomal phospholipase A was relatively unaffected by dust exposure. 7. It is suggested that the increase in surfactant amounts could be due to an increase in its synthesis without a corresponding alteration in its degradation."}
{"id": "PMID:202247", "title": "Cortisol induction of pulmonary maturation in the rabbit foetus. Its effects on enzymes related to phospholipid biosynthesis and on marker enzymes for subcellular organelles.", "content": "1. Cortisol treatment of rabbit foetuses in utero at 24 days gestation produced a significant decrease in the lung-weight to body-weight ratio compared with littermate controls by day 26. Histological examination revealed that the alveoli of the treated lungs were more open, the walls were thinner and the osmiophilic bodies were more numerous. 2. Cortisol treatment as described above produced significant increases (P<0.05) in the rates of incorporation of [(14)C]choline into phosphatidylcholine and of [(14)C]ethanolamine into phosphatidylethanolamine in vitro compared with littermate controls. This indicates that glucocorticoids produce an overall increase in phospholipid metabolism rather than a specific increase in phosphatidylcholine production. 3. The addition of 1,2-diacyl-sn-glycerols from egg phosphatidylcholine produced a 10-fold increase in the activity of choline phosphotransferase and a 3-fold increase in the activity of ethanolamine phosphotransferase in rabbit lung homogenates. The addition of 1,2-dipalmitoyl-sn-glycerol did not affect these activities. These results demonstrate that in the presence of exogenous 1,2-dipalmitoyl-sn-glycerol, the activities of these enzymes are dependent on the presence of endogenous 1,2-diacylglycerols. 4. Cortisol administration had no significant effect on the activity of choline phosphotransferase or ethanolamine phosphotransferase with endogenous or exogenously added diacylglycerols. The activities of other endoplasmic-reticulum enzymes (sn-glycerol 3-phosphate phosphatidyltransferase, sn-glycerol 3-phosphate acyltransferase and NADPH-cytochrome c reductase) were not significantly altered by the hormone administration. Oestrone sulphate sulphohydrolase activity was significantly decreased (P<0.05) by cortisol injection, but this effect varied with the foetuses from different does. 5. Cortisol administration had no effect on the activities of mitochondrial (monoamine oxidase, succinate dehydrogenase), plasma-membrane (5'-nucleotidase) or lysosomal (acid phosphatase, N-acetyl-beta-d-glucosaminidase) enzymes. The activity of membrane-associated phosphatidate phosphohydrolase, an enzyme associated with the osmiophilic granules of the type-II alveolar cells, was increased in the lungs of treated foetuses, but the difference was not significant (0.10>P>0.05).", "contents": "Cortisol induction of pulmonary maturation in the rabbit foetus. Its effects on enzymes related to phospholipid biosynthesis and on marker enzymes for subcellular organelles. 1. Cortisol treatment of rabbit foetuses in utero at 24 days gestation produced a significant decrease in the lung-weight to body-weight ratio compared with littermate controls by day 26. Histological examination revealed that the alveoli of the treated lungs were more open, the walls were thinner and the osmiophilic bodies were more numerous. 2. Cortisol treatment as described above produced significant increases (P<0.05) in the rates of incorporation of [(14)C]choline into phosphatidylcholine and of [(14)C]ethanolamine into phosphatidylethanolamine in vitro compared with littermate controls. This indicates that glucocorticoids produce an overall increase in phospholipid metabolism rather than a specific increase in phosphatidylcholine production. 3. The addition of 1,2-diacyl-sn-glycerols from egg phosphatidylcholine produced a 10-fold increase in the activity of choline phosphotransferase and a 3-fold increase in the activity of ethanolamine phosphotransferase in rabbit lung homogenates. The addition of 1,2-dipalmitoyl-sn-glycerol did not affect these activities. These results demonstrate that in the presence of exogenous 1,2-dipalmitoyl-sn-glycerol, the activities of these enzymes are dependent on the presence of endogenous 1,2-diacylglycerols. 4. Cortisol administration had no significant effect on the activity of choline phosphotransferase or ethanolamine phosphotransferase with endogenous or exogenously added diacylglycerols. The activities of other endoplasmic-reticulum enzymes (sn-glycerol 3-phosphate phosphatidyltransferase, sn-glycerol 3-phosphate acyltransferase and NADPH-cytochrome c reductase) were not significantly altered by the hormone administration. Oestrone sulphate sulphohydrolase activity was significantly decreased (P<0.05) by cortisol injection, but this effect varied with the foetuses from different does. 5. Cortisol administration had no effect on the activities of mitochondrial (monoamine oxidase, succinate dehydrogenase), plasma-membrane (5'-nucleotidase) or lysosomal (acid phosphatase, N-acetyl-beta-d-glucosaminidase) enzymes. The activity of membrane-associated phosphatidate phosphohydrolase, an enzyme associated with the osmiophilic granules of the type-II alveolar cells, was increased in the lungs of treated foetuses, but the difference was not significant (0.10>P>0.05)."}
{"id": "PMID:202248", "title": "Alterations in regulation of insulin biosynthesis in pregnancy and starvation studied in isolated rat islets of langerhans.", "content": "1. Insulin biosynthesis in isolated rat islets of Langerhans was determined by the incorporation of [(3)H]leucine into newly synthesized islet proteins. Anti-insulin serum covalently coupled to a solid phase (CNBr-activated Sepharose 4B) was used to separate the immunoreactive proinsulin and insulin from other islet proteins. This method was applied to a study of the regulation of insulin biosynthesis in isolated rat islets of Langerhans during pregnancy, and immediately after a period of food deprivation. 2. Islets isolated from pregnant rats showed an increased basal rate of synthesis compared with the non-pregnant controls. In addition, they showed a significant increase in biosynthesis of proinsulin and insulin in comparison with the normal islets over a range of glucose concentrations of 2-20mm. 3. Addition of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine significantly increased the insulin-synthetic response of normal islets over the glucose range 5-20mm, so that their glucose response approached that of islets from pregnant rats. 4. Normal female rates were injected with a long-acting progesterone derivative (hydroxyprogesterone hexanoate), to investigate the role of progesterone on the increased insulin biosynthesis observed in islets in pregnancy. There appeared to be no marked difference in insulin biosynthesis between the islets from the progesterone-injected and control rats in the presence of 2mm- or 6mm-glucose alone. However, in the presence of 4mm- or 6mm-glucose and 3-isobutyl-1-methylxanthine there was a significant increase in insulin biosynthesis in the progesterone-treated animals. 5. Total islet protein biosynthesis was determined by the incorporation of [(3)H]leucine into trichloroacetic acid-precipitable islet proteins. Islets isolated from normal rats showed a 1.6-fold increase in incorporation over the glucose concentration range 2-20mm, and this value remained unchanged during starvation; however, rates of incorporation were significantly raised in islets isolated from pregnant rats in the presence of 20mm-glucose. 6. Islets from starved and fed control rats were incubated in the presence of increasing concentrations of glucose or glucose+3-isobutyl-1-methylxanthine. The islets isolated from the starved animals showed a diminished insulin-synthetic response to glucose as compared with the controls; this response was partially restored to normal values by elevation of cyclic AMP concentrations by using 3-isobutyl-1-methylxanthine. 7. It is suggested that the alterations in glucose-stimulated insulin biosynthesis observed in islets during pregnancy and after a period of starvation could be attributable, at least in part, to a long-term alteration of the cyclic AMP system, and in pregnancy to a direct or indirect effect of progesterone on beta-cell function.", "contents": "Alterations in regulation of insulin biosynthesis in pregnancy and starvation studied in isolated rat islets of langerhans. 1. Insulin biosynthesis in isolated rat islets of Langerhans was determined by the incorporation of [(3)H]leucine into newly synthesized islet proteins. Anti-insulin serum covalently coupled to a solid phase (CNBr-activated Sepharose 4B) was used to separate the immunoreactive proinsulin and insulin from other islet proteins. This method was applied to a study of the regulation of insulin biosynthesis in isolated rat islets of Langerhans during pregnancy, and immediately after a period of food deprivation. 2. Islets isolated from pregnant rats showed an increased basal rate of synthesis compared with the non-pregnant controls. In addition, they showed a significant increase in biosynthesis of proinsulin and insulin in comparison with the normal islets over a range of glucose concentrations of 2-20mm. 3. Addition of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine significantly increased the insulin-synthetic response of normal islets over the glucose range 5-20mm, so that their glucose response approached that of islets from pregnant rats. 4. Normal female rates were injected with a long-acting progesterone derivative (hydroxyprogesterone hexanoate), to investigate the role of progesterone on the increased insulin biosynthesis observed in islets in pregnancy. There appeared to be no marked difference in insulin biosynthesis between the islets from the progesterone-injected and control rats in the presence of 2mm- or 6mm-glucose alone. However, in the presence of 4mm- or 6mm-glucose and 3-isobutyl-1-methylxanthine there was a significant increase in insulin biosynthesis in the progesterone-treated animals. 5. Total islet protein biosynthesis was determined by the incorporation of [(3)H]leucine into trichloroacetic acid-precipitable islet proteins. Islets isolated from normal rats showed a 1.6-fold increase in incorporation over the glucose concentration range 2-20mm, and this value remained unchanged during starvation; however, rates of incorporation were significantly raised in islets isolated from pregnant rats in the presence of 20mm-glucose. 6. Islets from starved and fed control rats were incubated in the presence of increasing concentrations of glucose or glucose+3-isobutyl-1-methylxanthine. The islets isolated from the starved animals showed a diminished insulin-synthetic response to glucose as compared with the controls; this response was partially restored to normal values by elevation of cyclic AMP concentrations by using 3-isobutyl-1-methylxanthine. 7. It is suggested that the alterations in glucose-stimulated insulin biosynthesis observed in islets during pregnancy and after a period of starvation could be attributable, at least in part, to a long-term alteration of the cyclic AMP system, and in pregnancy to a direct or indirect effect of progesterone on beta-cell function."}
{"id": "PMID:202249", "title": "Effect of buffer composition on binding of adenosine 3':5'-cyclic monophosphate by bovine adrenal extracts.", "content": "The binding of cyclic [3H] AMP by bovine adrenal extracts was studied in different buffer systems; 50 mM-Tris/HCl, pH 7.5, buffer containing 4mM-EDTA (disodium salt) offered advantages such as low non-specific interference and high binding affinity. 2-Mercaptoethanol decreased, but EDTA and theophylline increased, the specificity of cyclic [3H]AMP binding as expressed by the displacement of cyclic [3H]AMP by a 1000-fold excess of unlabelled cyclic GMP. The study indicated heterogeneity of the binding material. Mg2+-dependent binding may be eliminated in Tris/EDTA buffer. The heterogeneity and the specificity of intracellular cyclic AMP binders and their dependence in environmental factors should be considered in the evaluation of cyclic AMP binding and second-messenger systems.", "contents": "Effect of buffer composition on binding of adenosine 3':5'-cyclic monophosphate by bovine adrenal extracts. The binding of cyclic [3H] AMP by bovine adrenal extracts was studied in different buffer systems; 50 mM-Tris/HCl, pH 7.5, buffer containing 4mM-EDTA (disodium salt) offered advantages such as low non-specific interference and high binding affinity. 2-Mercaptoethanol decreased, but EDTA and theophylline increased, the specificity of cyclic [3H]AMP binding as expressed by the displacement of cyclic [3H]AMP by a 1000-fold excess of unlabelled cyclic GMP. The study indicated heterogeneity of the binding material. Mg2+-dependent binding may be eliminated in Tris/EDTA buffer. The heterogeneity and the specificity of intracellular cyclic AMP binders and their dependence in environmental factors should be considered in the evaluation of cyclic AMP binding and second-messenger systems."}
{"id": "PMID:202250", "title": "The sites of phosphorylation of rabbit cardiac troponin I by adenosine 3':5'-cyclic monophosphate-dependent protein kinase. Effect of interaction with troponin C.", "content": "1. Troponin I prepared from rabbit hearts contains 1.0-1.5 mol of P/mol when isolated by affinity chromatography. Most of the covalently bound phosphate is located in residues 1-48 of the molecule. 2. 3':5'-Cyclic AMP-dependent protein kinase catalyses phosphorylation at serine-20 and serine-146. Serine-20 is more rapidly phosphorylated than serine-146. 3. In troponin I prepared from frozen hearts by affinity chromatography about 0.3-0.5 mol of P/mol is associated with serine-20 and 0.8-1.0 mol of P/mol with other site(s) in residues 1-48 of the molecule. 4. Phosphorylation at serine-20 and servine-146 is not significantly inhibited by troponin C. 5. The mechansim of the interaction of troponin C with cardiac troponin I is discussed in the light of these results.", "contents": "The sites of phosphorylation of rabbit cardiac troponin I by adenosine 3':5'-cyclic monophosphate-dependent protein kinase. Effect of interaction with troponin C. 1. Troponin I prepared from rabbit hearts contains 1.0-1.5 mol of P/mol when isolated by affinity chromatography. Most of the covalently bound phosphate is located in residues 1-48 of the molecule. 2. 3':5'-Cyclic AMP-dependent protein kinase catalyses phosphorylation at serine-20 and serine-146. Serine-20 is more rapidly phosphorylated than serine-146. 3. In troponin I prepared from frozen hearts by affinity chromatography about 0.3-0.5 mol of P/mol is associated with serine-20 and 0.8-1.0 mol of P/mol with other site(s) in residues 1-48 of the molecule. 4. Phosphorylation at serine-20 and servine-146 is not significantly inhibited by troponin C. 5. The mechansim of the interaction of troponin C with cardiac troponin I is discussed in the light of these results."}
{"id": "PMID:202251", "title": "The effect of bovine tendon glycoprotein on the formation of fibrils from collagen solutions.", "content": "The formation of collagen fibrils under physiological conditions of ionic strength, pH and temperature was markedly affected by the presence of small amounts of bovine tendon glycoprotein. The absorbance of the gels at 400 nm was decreased, and they took longer to form. Over the range of concentration tested, the negative specific absorbance, -delta Asp., and the specific retardation, Rsp., both increased with the glycoprotein to collagen ratio. When added during the nucleation phase, glycoprotein was still able to exert its effect almost fully, and so must act to inhibit the later stages of fibril formation. Several pieces of evidence showed that glycoprotein acts via a weak binding to the collagen molecule. Electron microscopy established that fibrils formed in the presence of glycoprotein had a normal cross-striation pattern, but were significantly thinner than fibrils formed in control gets. The results suggest that glycoprotein could act in tissues to help regulate the diameter of collagen fibrils.", "contents": "The effect of bovine tendon glycoprotein on the formation of fibrils from collagen solutions. The formation of collagen fibrils under physiological conditions of ionic strength, pH and temperature was markedly affected by the presence of small amounts of bovine tendon glycoprotein. The absorbance of the gels at 400 nm was decreased, and they took longer to form. Over the range of concentration tested, the negative specific absorbance, -delta Asp., and the specific retardation, Rsp., both increased with the glycoprotein to collagen ratio. When added during the nucleation phase, glycoprotein was still able to exert its effect almost fully, and so must act to inhibit the later stages of fibril formation. Several pieces of evidence showed that glycoprotein acts via a weak binding to the collagen molecule. Electron microscopy established that fibrils formed in the presence of glycoprotein had a normal cross-striation pattern, but were significantly thinner than fibrils formed in control gets. The results suggest that glycoprotein could act in tissues to help regulate the diameter of collagen fibrils."}
{"id": "PMID:202252", "title": "Identification and partial characterization of an inhibitor of collagenase from rabbit bone.", "content": "Bone explants from foetal and newborn rabbits synthesize and release a collagenase inhibitor into culture media. Inhibitor production in the early days of culture is followed first by latent collagenase and subsequently active collagenase in the culture media. A reciprocal relationship exists between the amounts of free inhibitor and latent collagenase in culture media, suggesting strongly that the inhibitor is a component of the latent form of the enzyme. Over 90% of the inhibitory activity of culture media is associated with a fraction of apparent mol.wt. 30000 when determined by gel filtration on Ultrogel AcA 44. The inhibitor blocks the action of rabbit collagenase on both reconstituted collagen fibrils and collagen in solution. It inhibits the action of either active collagenase or latent collagenase activated by 4-aminophenylmercuric acetate. Latent collagenase activated by trypsin is usually much less susceptible to inhibition. The activity of the inhibitor is destroyed by heat, by incubation with either trypsin or chymotrypsin and by 4-aminophenylmercuric acetate. Collagenase activity can be recovered from complexes of enzyme (activated with 4-aminophenylmercuric acetate) with free inhibitor by incubation with either trypsin or 4-aminophenylmercuric acetate, at concentrations similar to those that activate latent collagenase from culture media. The rabbit bone inhibitor does not affect the activity of bacterial collagenase, but blocks the action of collagenases not only from a variety of rabbit tissues but also from other mammalian species.", "contents": "Identification and partial characterization of an inhibitor of collagenase from rabbit bone. Bone explants from foetal and newborn rabbits synthesize and release a collagenase inhibitor into culture media. Inhibitor production in the early days of culture is followed first by latent collagenase and subsequently active collagenase in the culture media. A reciprocal relationship exists between the amounts of free inhibitor and latent collagenase in culture media, suggesting strongly that the inhibitor is a component of the latent form of the enzyme. Over 90% of the inhibitory activity of culture media is associated with a fraction of apparent mol.wt. 30000 when determined by gel filtration on Ultrogel AcA 44. The inhibitor blocks the action of rabbit collagenase on both reconstituted collagen fibrils and collagen in solution. It inhibits the action of either active collagenase or latent collagenase activated by 4-aminophenylmercuric acetate. Latent collagenase activated by trypsin is usually much less susceptible to inhibition. The activity of the inhibitor is destroyed by heat, by incubation with either trypsin or chymotrypsin and by 4-aminophenylmercuric acetate. Collagenase activity can be recovered from complexes of enzyme (activated with 4-aminophenylmercuric acetate) with free inhibitor by incubation with either trypsin or 4-aminophenylmercuric acetate, at concentrations similar to those that activate latent collagenase from culture media. The rabbit bone inhibitor does not affect the activity of bacterial collagenase, but blocks the action of collagenases not only from a variety of rabbit tissues but also from other mammalian species."}
{"id": "PMID:202253", "title": "Synthesis of glycosaminoglycans by human embryonic lung fibroblasts. Different distribution of heparan sulphate, chondroitin sulphate and dermatan sulphate in various fractions of cell culture.", "content": "Foetal human lung fibroblasts, grown in monolayer, were allowed to incorporate (35)SO(4) (2-) for various periods of time. (35)S-labelled macromolecular anionic products were isolated from the medium, a trypsin digest of the cells in monolayer and the cell residue. The various radioactive polysaccharides were identified as heparan sulphate and a galactosaminoglycan population (chondroitin sulphate and dermatan sulphate) by ion-exchange chromatography and by differential degradations with HNO(2) and chondroitinase ABC. Most of the heparan sulphate was found in the trypsin digest, whereas the galactosaminoglycan components were largely confined to the medium. Electrophoretic studies on the various (35)S-labelled galactosaminoglycans suggested the presence of a separate chondroitin sulphate component (i.e. a glucuronic acid-rich galactosaminoglycan). The (35)S-labelled galactosaminoglycans were subjected to periodate oxidation of l-iduronic acid residues followed by scission in alkali. A periodate-resistant polymer fraction was obtained, which could be degraded to disaccharides by chondroitinase AC. However, most of the (35)S-labelled galactosaminoglycans were extensively degraded by periodate oxidation-alkaline elimination. The oligosaccharides obtained were essentially resistant to chondroitinase AC, indicating that the iduronic acid-rich galactosaminoglycans (i.e. dermatan sulphate) were composed largely of repeating units containing sulphated or non-sulphated l-iduronic acid residues. The l-iduronic acid residues present in dermatan sulphate derived from the medium and the trypsin digest contained twice as much ester sulphate as did material associated with the cells. The content of d-glucuronic acid was low and similar in all three fractions. The relative distribution of glycosaminoglycans among the various fractions obtained from cultured lung fibroblasts was distinctly different from that of skin fibroblasts [Malmstr\u00f6m, Carlstedt, Aberg & Fransson (1975) Biochem. J.151, 477-489]. Moreover, subtle differences in co-polymeric structure of dermatan sulphate isolated from the two cell types could be detected.", "contents": "Synthesis of glycosaminoglycans by human embryonic lung fibroblasts. Different distribution of heparan sulphate, chondroitin sulphate and dermatan sulphate in various fractions of cell culture. Foetal human lung fibroblasts, grown in monolayer, were allowed to incorporate (35)SO(4) (2-) for various periods of time. (35)S-labelled macromolecular anionic products were isolated from the medium, a trypsin digest of the cells in monolayer and the cell residue. The various radioactive polysaccharides were identified as heparan sulphate and a galactosaminoglycan population (chondroitin sulphate and dermatan sulphate) by ion-exchange chromatography and by differential degradations with HNO(2) and chondroitinase ABC. Most of the heparan sulphate was found in the trypsin digest, whereas the galactosaminoglycan components were largely confined to the medium. Electrophoretic studies on the various (35)S-labelled galactosaminoglycans suggested the presence of a separate chondroitin sulphate component (i.e. a glucuronic acid-rich galactosaminoglycan). The (35)S-labelled galactosaminoglycans were subjected to periodate oxidation of l-iduronic acid residues followed by scission in alkali. A periodate-resistant polymer fraction was obtained, which could be degraded to disaccharides by chondroitinase AC. However, most of the (35)S-labelled galactosaminoglycans were extensively degraded by periodate oxidation-alkaline elimination. The oligosaccharides obtained were essentially resistant to chondroitinase AC, indicating that the iduronic acid-rich galactosaminoglycans (i.e. dermatan sulphate) were composed largely of repeating units containing sulphated or non-sulphated l-iduronic acid residues. The l-iduronic acid residues present in dermatan sulphate derived from the medium and the trypsin digest contained twice as much ester sulphate as did material associated with the cells. The content of d-glucuronic acid was low and similar in all three fractions. The relative distribution of glycosaminoglycans among the various fractions obtained from cultured lung fibroblasts was distinctly different from that of skin fibroblasts [Malmstr\u00f6m, Carlstedt, Aberg & Fransson (1975) Biochem. J.151, 477-489]. Moreover, subtle differences in co-polymeric structure of dermatan sulphate isolated from the two cell types could be detected."}
{"id": "PMID:202254", "title": "The electron-transfer reaction between azurin and the cytochrome c oxidase from Pseudomonas aeruginosa.", "content": "A stopped-flow investigation of the electron-transfer reaction between oxidized azurin and reduced Pseudomonas aeruginosa cytochrome c-551 oxidase and between reduced azurin and oxidized Ps. aeruginosa cytochrome c-551 oxidase was performed. Electrons leave and enter the oxidase molecule via its haem c component, with the oxidation and reduction of the haem d1 occurring by internal electron transfer. The reaction mechanism in both directions is complex. In the direction of oxidase oxidation, two phases assigned on the basis of difference spectra to haem c proceed with rate constants of 3.2 X 10(5)M-1-S-1 and 2.0 X 10(4)M-1-S-1, whereas the haem d1 oxidation occurs at 0.35 +/- 0.1S-1. Addition of CO to the reduced enzyme profoundly modifies the rate of haem c oxidation, with the faster process tending towards a rate limit of 200S-1. Reduction of the oxidase was similarly complex, with a fast haem c phase tending to a rate limit of 120S-1, and a slower phase with a second-order rate of 1.5 X 10(4)M-1-S-1; the internal transfer rate in this direction was o.25 +/- 0.1S-1. These results have been applied to a kinetic model originally developed from temperature-jump studies.", "contents": "The electron-transfer reaction between azurin and the cytochrome c oxidase from Pseudomonas aeruginosa. A stopped-flow investigation of the electron-transfer reaction between oxidized azurin and reduced Pseudomonas aeruginosa cytochrome c-551 oxidase and between reduced azurin and oxidized Ps. aeruginosa cytochrome c-551 oxidase was performed. Electrons leave and enter the oxidase molecule via its haem c component, with the oxidation and reduction of the haem d1 occurring by internal electron transfer. The reaction mechanism in both directions is complex. In the direction of oxidase oxidation, two phases assigned on the basis of difference spectra to haem c proceed with rate constants of 3.2 X 10(5)M-1-S-1 and 2.0 X 10(4)M-1-S-1, whereas the haem d1 oxidation occurs at 0.35 +/- 0.1S-1. Addition of CO to the reduced enzyme profoundly modifies the rate of haem c oxidation, with the faster process tending towards a rate limit of 200S-1. Reduction of the oxidase was similarly complex, with a fast haem c phase tending to a rate limit of 120S-1, and a slower phase with a second-order rate of 1.5 X 10(4)M-1-S-1; the internal transfer rate in this direction was o.25 +/- 0.1S-1. These results have been applied to a kinetic model originally developed from temperature-jump studies."}
{"id": "PMID:202255", "title": "A simple radioassay for angiotensin-converting enzyme.", "content": "Angiotensin-converting enzyme can be measured by the rate of release of 3H-labelled hippurate from p-[3H]benzoylglycylglycylglycine. The product is separable from the substrate by extraction of acidified reaction mixtures with ethyl acetate. Assay results for human serum angiotensin-converting enzyme can be obtained within 1.5 h of receipt of serum samples. Within the limits tested, the assay appears to be specific. However, interference by hitherto unrecognized enzymes of abnormal sera must be ruled out.", "contents": "A simple radioassay for angiotensin-converting enzyme. Angiotensin-converting enzyme can be measured by the rate of release of 3H-labelled hippurate from p-[3H]benzoylglycylglycylglycine. The product is separable from the substrate by extraction of acidified reaction mixtures with ethyl acetate. Assay results for human serum angiotensin-converting enzyme can be obtained within 1.5 h of receipt of serum samples. Within the limits tested, the assay appears to be specific. However, interference by hitherto unrecognized enzymes of abnormal sera must be ruled out."}
{"id": "PMID:202256", "title": "Effect of lutropin on phosphorylation of endogenous proteins in testis leydig cells. Correlation with testosterone production.", "content": "The effect of lutropin on phosphorylation of endogenous proteins in testis Leydig cells was investigated, by incubating purified Leydig cells with lutropin and [(32)P]P(i) followed by sodium dodecyl sulphate/polyacrylamide-slab gel electrophoresis of the [(32)P]phosphoproteins. The radioactivity of the proteins was quantified by densitometry of the radio-autograms obtained. The following results were obtained. 1. Lutropin increased the amount of (32)P incorporated into three proteins (A, B and C) with apparent mol.wts. of 14300, 57000 and 77600 respectively. 2. The increase in incorporation of (32)P into these proteins was detectable within 5min, reaching a maximum in approx. 20min. 3. The (32)P incorporated into protein B (but not proteins A and C) was significantly increased with 0.1 and 1.0ng of lutropin/ml. Incorporation of (32)P into all three proteins was significantly increased with 10ng of lutropin/ml, reaching a maximum with 100ng/ml. 4. Testosterone production was significantly increased with 1ng of lutropin/ml, and between 10 and 1000ng/ml the degree of stimulation of testosterone production and incorporation of (32)P into proteins A, B and C was similar. 5. Cyclic AMP production was significantly increased with 10ng of lutropin/ml and had not reached a maximum with 1000ng/ml. 6. In Leydig cells isolated from hypophysectomized rats 3h after injection of choriogonadotropin in vivo, phosphoproteins with the same molecular weights as proteins A, B and C were found. No further increases in incorporation of (32)P into these proteins were obtained when lutropin was added to the Leydig cells in vitro. 7. Dibutyryl cyclic AMP (but not follitropin or testosterone) also stimulated the incorporation of (32)P into proteins A, B and C in Leydig cells.", "contents": "Effect of lutropin on phosphorylation of endogenous proteins in testis leydig cells. Correlation with testosterone production. The effect of lutropin on phosphorylation of endogenous proteins in testis Leydig cells was investigated, by incubating purified Leydig cells with lutropin and [(32)P]P(i) followed by sodium dodecyl sulphate/polyacrylamide-slab gel electrophoresis of the [(32)P]phosphoproteins. The radioactivity of the proteins was quantified by densitometry of the radio-autograms obtained. The following results were obtained. 1. Lutropin increased the amount of (32)P incorporated into three proteins (A, B and C) with apparent mol.wts. of 14300, 57000 and 77600 respectively. 2. The increase in incorporation of (32)P into these proteins was detectable within 5min, reaching a maximum in approx. 20min. 3. The (32)P incorporated into protein B (but not proteins A and C) was significantly increased with 0.1 and 1.0ng of lutropin/ml. Incorporation of (32)P into all three proteins was significantly increased with 10ng of lutropin/ml, reaching a maximum with 100ng/ml. 4. Testosterone production was significantly increased with 1ng of lutropin/ml, and between 10 and 1000ng/ml the degree of stimulation of testosterone production and incorporation of (32)P into proteins A, B and C was similar. 5. Cyclic AMP production was significantly increased with 10ng of lutropin/ml and had not reached a maximum with 1000ng/ml. 6. In Leydig cells isolated from hypophysectomized rats 3h after injection of choriogonadotropin in vivo, phosphoproteins with the same molecular weights as proteins A, B and C were found. No further increases in incorporation of (32)P into these proteins were obtained when lutropin was added to the Leydig cells in vitro. 7. Dibutyryl cyclic AMP (but not follitropin or testosterone) also stimulated the incorporation of (32)P into proteins A, B and C in Leydig cells."}
{"id": "PMID:202257", "title": "Use of octadecasilyl-silica for the extraction and purification of peptides in biological samples. Application to the identification of circulating metabolites of corticotropin-(1-24)-tetracosapeptide and somatostatin in vivo.", "content": "Peptides can be adsorbed on octadecasilyl-silica from large volumes of aqueous solution and eluted with aqueous solvent mixtures containing methanol or acetonitrile. These properties may be used for the extraction and purification of peptide fragments in plasma samples collected from rats. After intravenous injection of Synacthen [corticotropin-(1-24)-tetracosapeptide], it was shown that within 2 min the main circulating products were intact peptide and its sulphoxide. In addition, a number of fragments indicative of cleavage at the N- and C-termini were present. Most of the products formed from Synacthen have low biological activity. Somatostatin was rapidly cleaved in vivo and in vitro to a single product, which probably retains biological activity. The absence of other circulating products suggests that somatostatin is only inactivated once it leaves the circulation.", "contents": "Use of octadecasilyl-silica for the extraction and purification of peptides in biological samples. Application to the identification of circulating metabolites of corticotropin-(1-24)-tetracosapeptide and somatostatin in vivo. Peptides can be adsorbed on octadecasilyl-silica from large volumes of aqueous solution and eluted with aqueous solvent mixtures containing methanol or acetonitrile. These properties may be used for the extraction and purification of peptide fragments in plasma samples collected from rats. After intravenous injection of Synacthen [corticotropin-(1-24)-tetracosapeptide], it was shown that within 2 min the main circulating products were intact peptide and its sulphoxide. In addition, a number of fragments indicative of cleavage at the N- and C-termini were present. Most of the products formed from Synacthen have low biological activity. Somatostatin was rapidly cleaved in vivo and in vitro to a single product, which probably retains biological activity. The absence of other circulating products suggests that somatostatin is only inactivated once it leaves the circulation."}
{"id": "PMID:202258", "title": "Biosynthesis and release of glycoproteins by human skin fibroblasts in culture.", "content": "1. Confluent human skin fibroblasts maintained in a chemically defined medium incorporate l-[1-(3)H]fucose in a linear manner with time into non-diffusible macromolecules for up to 48h. Chromatographic analysis demonstrated that virtually all the macromolecule-associated (3)H was present as [(3)H]fucose. 2. Equilibrium CsCl-density-gradient centrifugation established that [(3)H]fucose-labelled macromolecules released into the medium were predominantly glycoproteins. Confirmation of this finding was provided by molecular-size analyses of the [(3)H]fucose-labelled material before and after trypsin digestion. 3. The [(3)H]fucose-labelled glycoproteins released into fibroblast culture medium were analysed by gel-filtration chromatography and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. These techniques demonstrated that the major fucosylated glycoprotein had an apparent mol.wt. of 230000-250000; several minor labelled species were also detected. 4. Dual-labelling experiments with [(3)H]fucose and (14)C-labelled amino acids indicated that the major fucosylated glycoprotein was synthesized de novo by cultured fibroblasts. The non-collagenous nature of this glycoprotein was established by three independent methods. 5. Gel-filtration analysis before and after reduction with dithiothreitol showed that the major glycoprotein occurs as a disulphide-bonded dimer when analysed under denaturing conditions. Further experiments demonstrated that this glycoprotein was the predominant labelled species released into the medium when fibroblasts were incubated with [(35)S]cysteine. 6. The relationship between the major fucosylated glycoprotein and a glycoprotein, or group of glycoproteins, variously known as fibronectin, LETS protein, cell-surface protein etc., is discussed.", "contents": "Biosynthesis and release of glycoproteins by human skin fibroblasts in culture. 1. Confluent human skin fibroblasts maintained in a chemically defined medium incorporate l-[1-(3)H]fucose in a linear manner with time into non-diffusible macromolecules for up to 48h. Chromatographic analysis demonstrated that virtually all the macromolecule-associated (3)H was present as [(3)H]fucose. 2. Equilibrium CsCl-density-gradient centrifugation established that [(3)H]fucose-labelled macromolecules released into the medium were predominantly glycoproteins. Confirmation of this finding was provided by molecular-size analyses of the [(3)H]fucose-labelled material before and after trypsin digestion. 3. The [(3)H]fucose-labelled glycoproteins released into fibroblast culture medium were analysed by gel-filtration chromatography and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. These techniques demonstrated that the major fucosylated glycoprotein had an apparent mol.wt. of 230000-250000; several minor labelled species were also detected. 4. Dual-labelling experiments with [(3)H]fucose and (14)C-labelled amino acids indicated that the major fucosylated glycoprotein was synthesized de novo by cultured fibroblasts. The non-collagenous nature of this glycoprotein was established by three independent methods. 5. Gel-filtration analysis before and after reduction with dithiothreitol showed that the major glycoprotein occurs as a disulphide-bonded dimer when analysed under denaturing conditions. Further experiments demonstrated that this glycoprotein was the predominant labelled species released into the medium when fibroblasts were incubated with [(35)S]cysteine. 6. The relationship between the major fucosylated glycoprotein and a glycoprotein, or group of glycoproteins, variously known as fibronectin, LETS protein, cell-surface protein etc., is discussed."}
{"id": "PMID:202259", "title": "Relationship between the reduction of oxygen, artificial acceptors and cytochrome P-450 by NADPH--cytochrome c reductase.", "content": "The interaction of NADPH--cytochrome c reductase with oxygen, artificial acceptors and cytochrome P-450 was studied. The generation of superoxide anion radicals (O2-.) from the oxidation of adrenaline to adrenochrome catalysed by NADPH--cytochrome c reductase proceeds independently of the interaction of the enzyme with the artificial anaerobic acceptors cytochrome c or 2,6-dichlorophenol-indophenol. Propyl 3,4,5-trihydroxybenzoate inhibited competitively the adrenaline oxidation by isolated NADPH--cytochrome c reductase (Ki 3.2--4.7 micrometer) and inhibited non-competitively the cytochrome c reduction (Ki 92--109 micrometer). In contrast with the process of electron transfer to cytochrome c, the rate of reduction of cytochrome P-450 and the rate of oxidation of adrenaline in liver microsomal fraction are correlated. Hexobarbital increases the Vmax. of adrenaline oxidation without affecting the Km value, whereas metyrapone, a metabolic inhibitor decreases Vmax. without affecting the Km. From the results obtained, some conclusions about NADPH--cytochrome c reductase function were made.", "contents": "Relationship between the reduction of oxygen, artificial acceptors and cytochrome P-450 by NADPH--cytochrome c reductase. The interaction of NADPH--cytochrome c reductase with oxygen, artificial acceptors and cytochrome P-450 was studied. The generation of superoxide anion radicals (O2-.) from the oxidation of adrenaline to adrenochrome catalysed by NADPH--cytochrome c reductase proceeds independently of the interaction of the enzyme with the artificial anaerobic acceptors cytochrome c or 2,6-dichlorophenol-indophenol. Propyl 3,4,5-trihydroxybenzoate inhibited competitively the adrenaline oxidation by isolated NADPH--cytochrome c reductase (Ki 3.2--4.7 micrometer) and inhibited non-competitively the cytochrome c reduction (Ki 92--109 micrometer). In contrast with the process of electron transfer to cytochrome c, the rate of reduction of cytochrome P-450 and the rate of oxidation of adrenaline in liver microsomal fraction are correlated. Hexobarbital increases the Vmax. of adrenaline oxidation without affecting the Km value, whereas metyrapone, a metabolic inhibitor decreases Vmax. without affecting the Km. From the results obtained, some conclusions about NADPH--cytochrome c reductase function were made."}
{"id": "PMID:202260", "title": "The effect of chronic diabetes, induced by streptozotocin, on the activities of some enzymes of glycerolipid synthesis in rat liver.", "content": "1. Rats were injected with a single dose of 35mg of streptozotocin/kg body wt. They exhibited a diabetes that was characterized by glycosuria, polyuria, polydipsia, hyperphagia, hyperglycaemia, increased concentrations of unesterified fatty acids, glycerol and triacylglycerols in the serum and an increased activity of glucose 6-phosphatase in the liver. 2. After 10 weeks the hepatic activities of the microsomal glycerol phosphate acyltransferase, phosphatidate phosphohydrolase, phosphatidate cytidylyltransferase, diacylglycerol acyltransferase, choline phosphotransferase, CDP-diacylglycerol--inositol phosphatidyltransferase and the soluble phosphatidate phosphohydrolase were measured. 3. The only significant changes were an increase in the activity of the soluble phosphatidate phosphohydrolase and a decrease in that of the CDP-diacylglycerol--inositol phosphatidyltransferase in the diabetic rats. 4. These results are discussed in relation to the control of glycerolipid synthesis.", "contents": "The effect of chronic diabetes, induced by streptozotocin, on the activities of some enzymes of glycerolipid synthesis in rat liver. 1. Rats were injected with a single dose of 35mg of streptozotocin/kg body wt. They exhibited a diabetes that was characterized by glycosuria, polyuria, polydipsia, hyperphagia, hyperglycaemia, increased concentrations of unesterified fatty acids, glycerol and triacylglycerols in the serum and an increased activity of glucose 6-phosphatase in the liver. 2. After 10 weeks the hepatic activities of the microsomal glycerol phosphate acyltransferase, phosphatidate phosphohydrolase, phosphatidate cytidylyltransferase, diacylglycerol acyltransferase, choline phosphotransferase, CDP-diacylglycerol--inositol phosphatidyltransferase and the soluble phosphatidate phosphohydrolase were measured. 3. The only significant changes were an increase in the activity of the soluble phosphatidate phosphohydrolase and a decrease in that of the CDP-diacylglycerol--inositol phosphatidyltransferase in the diabetic rats. 4. These results are discussed in relation to the control of glycerolipid synthesis."}
{"id": "PMID:202261", "title": "Rapid isolation of plasma membranes in high yield from cultured fibroblasts.", "content": "1. A method was developed which allows the rapid preparation of pure plasma membranes in high yield from cultured fibroblasts. 2. Cells are lysed in hypo-osmotic borate/EDTA and, after differential centrifugation, the membranes collected by centrifugation on a sucrose barrier. 3. Electron microscopy of the isolated material shows large membrane vesicles essentially free from contaminating organelles. 4. There is no detectable activity of the endoplasmic-reticulum enzyme marker, NADH2--lipoamide oxidoreductase (EC 1.6.4.3), and that of succinate dehydrogenase (EC 1.3.99.1), a marker for mitochondria, is substantially decreased. Chemical compositions are in good agreement with previous observations. 5. This study confirms the usefulness of applied isotopic markers for isolating plasma membranes.", "contents": "Rapid isolation of plasma membranes in high yield from cultured fibroblasts. 1. A method was developed which allows the rapid preparation of pure plasma membranes in high yield from cultured fibroblasts. 2. Cells are lysed in hypo-osmotic borate/EDTA and, after differential centrifugation, the membranes collected by centrifugation on a sucrose barrier. 3. Electron microscopy of the isolated material shows large membrane vesicles essentially free from contaminating organelles. 4. There is no detectable activity of the endoplasmic-reticulum enzyme marker, NADH2--lipoamide oxidoreductase (EC 1.6.4.3), and that of succinate dehydrogenase (EC 1.3.99.1), a marker for mitochondria, is substantially decreased. Chemical compositions are in good agreement with previous observations. 5. This study confirms the usefulness of applied isotopic markers for isolating plasma membranes."}
{"id": "PMID:202262", "title": "Midpoint redox potentials of plant and algal ferredoxins.", "content": "Midpoint potentials of plant-type ferredoxins from a range of sources were measured by redox titrations combined with electron-paramagnetic-resonance spectroscopy. For ferredoxins from higher plants, green algae and most red algae, the midpoint potentials (at pH 8.0) were between --390 and --425 mV. Values for the major ferredoxin fractions from blue-green algae were less negative (between --325 and --390 mV). In addition, Spirulina maxima and Nostoc strain MAC contain second minor ferredoxin components with a different potential, --305 mV (the highest so far measured for a plant-algal ferrodoxin) for Spirulina ferrodoxin II, and --455 mV (the lowest so far measured for a plant-algal ferredoxin) for Nostoc strain MAC ferredoxin II. However, two ferredoxins extracted from a variety of the higher plant Pisum sativum (pea) had midpoint potentials that were only slightly different from each other. These values are discussed in terms of possible roles for the ferredoxins in addition to their involvement in photosynthetic electron transport.", "contents": "Midpoint redox potentials of plant and algal ferredoxins. Midpoint potentials of plant-type ferredoxins from a range of sources were measured by redox titrations combined with electron-paramagnetic-resonance spectroscopy. For ferredoxins from higher plants, green algae and most red algae, the midpoint potentials (at pH 8.0) were between --390 and --425 mV. Values for the major ferredoxin fractions from blue-green algae were less negative (between --325 and --390 mV). In addition, Spirulina maxima and Nostoc strain MAC contain second minor ferredoxin components with a different potential, --305 mV (the highest so far measured for a plant-algal ferrodoxin) for Spirulina ferrodoxin II, and --455 mV (the lowest so far measured for a plant-algal ferredoxin) for Nostoc strain MAC ferredoxin II. However, two ferredoxins extracted from a variety of the higher plant Pisum sativum (pea) had midpoint potentials that were only slightly different from each other. These values are discussed in terms of possible roles for the ferredoxins in addition to their involvement in photosynthetic electron transport."}
{"id": "PMID:202263", "title": "Enhancement of the anti-anabolic response to adenosine 3':5'-cyclic monophosphate during development. The inhibition of hepatic protein synthesis.", "content": "Cyclic AMP causes an age-dependent inhibition of protein synthesis in rat liver. The onset of inhibition is about 10--12 days after birth. The developmental response to cyclic AMP is associated with a change in the microsomal component of the protein-synthesizing system.", "contents": "Enhancement of the anti-anabolic response to adenosine 3':5'-cyclic monophosphate during development. The inhibition of hepatic protein synthesis. Cyclic AMP causes an age-dependent inhibition of protein synthesis in rat liver. The onset of inhibition is about 10--12 days after birth. The developmental response to cyclic AMP is associated with a change in the microsomal component of the protein-synthesizing system."}
{"id": "PMID:202264", "title": "Modulation of the response of bovine adrenocortical adenylate cyclase to corticotropin.", "content": "An assessment was made of some of the basic parameters responsible for the modulation of adenylate cyclase activity in a bovine adrenocortical plasma-membrane preparation. When determined at 0.1 mM-ATP, basal adenylate cyclase activity increased with increasing MgCl2 concentrations, whereas in the presence of corticotropin activity was essentially maximal at 10mM-MgCl2; high concentrations (25mM) of MgCl2 inhibited adenylate cyclase activity determined in the presence of both corticotropin and GTP. At all MgCl2 concentrations, corticotropin and GTP activated the enzyme in a synergistic fashion. The magnitude of the stimulation of basal activity produced by corticotropin was a function of Mg2+ concentration, whereas that produced by GTP appeared largely independent of Mg2+ concentration. Adenylate cyclase activity in the bovine adrenal membrane was half-maximally stimulated by corticotropin concentrations in the range 0.3--1.0 nM. The concentration of corticotropin evoking half-maximum response was not significantly affected by raising the free Mg2+ concentration from 0.4 to 4.9 mM, nor by the presence of GTP. In the presence of GTP, high concentrations (over 1 micrometer) of corticotropin inhibited adenylate cyclase activity, although no inhibition was apparent in the absence of guanine nucleotide.", "contents": "Modulation of the response of bovine adrenocortical adenylate cyclase to corticotropin. An assessment was made of some of the basic parameters responsible for the modulation of adenylate cyclase activity in a bovine adrenocortical plasma-membrane preparation. When determined at 0.1 mM-ATP, basal adenylate cyclase activity increased with increasing MgCl2 concentrations, whereas in the presence of corticotropin activity was essentially maximal at 10mM-MgCl2; high concentrations (25mM) of MgCl2 inhibited adenylate cyclase activity determined in the presence of both corticotropin and GTP. At all MgCl2 concentrations, corticotropin and GTP activated the enzyme in a synergistic fashion. The magnitude of the stimulation of basal activity produced by corticotropin was a function of Mg2+ concentration, whereas that produced by GTP appeared largely independent of Mg2+ concentration. Adenylate cyclase activity in the bovine adrenal membrane was half-maximally stimulated by corticotropin concentrations in the range 0.3--1.0 nM. The concentration of corticotropin evoking half-maximum response was not significantly affected by raising the free Mg2+ concentration from 0.4 to 4.9 mM, nor by the presence of GTP. In the presence of GTP, high concentrations (over 1 micrometer) of corticotropin inhibited adenylate cyclase activity, although no inhibition was apparent in the absence of guanine nucleotide."}
{"id": "PMID:202265", "title": "The phosphorylation potential generated by respiring bovine heart submitochondrial particles.", "content": "A phosphorylation potential deltaGp, where deltaGp = deltaGo' + RT2.303 log  ([ATP]/([ADP][Pi])), of approx. 44.3 kJ.mol-1 (10.6 kcal.mol-1) was generated by submitochondrial particles that were oxidizing either NADH or succinate. Addition of adenylyl imidodiphosphate, which should suppress adenosine triphosphatase activity of any uncoupled particles, did not raise the phosphorylation potential. Raising the Pi concentration slightly increased the magnitude of the value for [ATP]/[ADP], but this did not fully compensate for the increased Pi concentration, so that the phosphorylation potential decreased slightly as the Pi concentration was raised. The phosphorylation potential developed by submitochondrial particles is lower than that generated by phosphorylating membrane vesicles from some bacteria, and is also less than that developed externally by mitochondria, but is strikingly close to the phosphorylation potential that is generated internally by mitochondria.", "contents": "The phosphorylation potential generated by respiring bovine heart submitochondrial particles. A phosphorylation potential deltaGp, where deltaGp = deltaGo' + RT2.303 log  ([ATP]/([ADP][Pi])), of approx. 44.3 kJ.mol-1 (10.6 kcal.mol-1) was generated by submitochondrial particles that were oxidizing either NADH or succinate. Addition of adenylyl imidodiphosphate, which should suppress adenosine triphosphatase activity of any uncoupled particles, did not raise the phosphorylation potential. Raising the Pi concentration slightly increased the magnitude of the value for [ATP]/[ADP], but this did not fully compensate for the increased Pi concentration, so that the phosphorylation potential decreased slightly as the Pi concentration was raised. The phosphorylation potential developed by submitochondrial particles is lower than that generated by phosphorylating membrane vesicles from some bacteria, and is also less than that developed externally by mitochondria, but is strikingly close to the phosphorylation potential that is generated internally by mitochondria."}
{"id": "PMID:202266", "title": "Phosphorylation of the inhibitory subunit of troponin in perfused hearts of mice deficient in phosphorylase kinase. Evidence for the phosphorylation of troponin by adenosine 3':5'-phosphate-dependent protein kinase in vivo.", "content": "When hearts from control and phosphorylase kinase-deficient (I strain) mice were perfused with 0.1 micrometer-DL-isoprenaline, there was a parallel increase in contraction, cyclic AMP concentration and troponin I phosphorylation. However, there was no increase in phosphorylase a in the I-strain hearts, whereas the control hearts showed a large increase. Assays of I-strain heart extracts showed a normal cyclic AMP-dependent protein kinase activity but no phosphorylase kinase activity. It is concluded that troponin I is phosphorylated in intact hearts by protein kinase and not phosphorylase kinase.", "contents": "Phosphorylation of the inhibitory subunit of troponin in perfused hearts of mice deficient in phosphorylase kinase. Evidence for the phosphorylation of troponin by adenosine 3':5'-phosphate-dependent protein kinase in vivo. When hearts from control and phosphorylase kinase-deficient (I strain) mice were perfused with 0.1 micrometer-DL-isoprenaline, there was a parallel increase in contraction, cyclic AMP concentration and troponin I phosphorylation. However, there was no increase in phosphorylase a in the I-strain hearts, whereas the control hearts showed a large increase. Assays of I-strain heart extracts showed a normal cyclic AMP-dependent protein kinase activity but no phosphorylase kinase activity. It is concluded that troponin I is phosphorylated in intact hearts by protein kinase and not phosphorylase kinase."}
{"id": "PMID:202267", "title": "Protein phosphorylation in normal and neoplastic development. Cyclic AMP-dependent protein kinase activity in urethane-induced pulmonary tumours.", "content": "The cyclic AMP-dependent protein kinase specific activities of cytosol fractions from urethane-induced lung tumours and from normal mouse lung were determined. Both basal and cyclic AMP-stimulated activities in tumours were twofold higher than those of normal lung. Since neonatal and adult lung cytosols have identical kinase activities, the high activity in tumours appears to be a tumour-specific property.", "contents": "Protein phosphorylation in normal and neoplastic development. Cyclic AMP-dependent protein kinase activity in urethane-induced pulmonary tumours. The cyclic AMP-dependent protein kinase specific activities of cytosol fractions from urethane-induced lung tumours and from normal mouse lung were determined. Both basal and cyclic AMP-stimulated activities in tumours were twofold higher than those of normal lung. Since neonatal and adult lung cytosols have identical kinase activities, the high activity in tumours appears to be a tumour-specific property."}
{"id": "PMID:202292", "title": "[Prevalence of complement fixation antibodies of cytomegalovirus in various Mexican communities].", "content": "In 1962 Weller and Hanshaw reported evidence of the teratogenic potential of CMV (cytomegalic inclusion disease virus or cytomegalovirus) for the developing human embryo. Some other investigators have also shown that CMV may be involved in different pathological conditions, that it is an ubiquous agent capable of producing a high incidence of infection, usually asymptomatic, under quite diverse ecological conditions, and that the proportion of individuals that have been in contact with the virus increases with age, which is evidenced by the frequency of seropositivity to the specific antigen. The high prevalence of CF antibodies to CMV in the studied groups from the state of Chiapas, particularly in Lacanj\u00e1 where 45% of the total population (120 inhabitants) was included in the survey, indicates a wide dissemination of this virus. Lower levels of seropositivity were found among children from the Mexico City group, but they are higher than those found in serological surveys in children from Huixquilucan (state of Mexico) and from Seattle and Dallas in U.S.A. The possible implications of some seroepidemiological characteristics of CMV infection are discussed.", "contents": "[Prevalence of complement fixation antibodies of cytomegalovirus in various Mexican communities]. In 1962 Weller and Hanshaw reported evidence of the teratogenic potential of CMV (cytomegalic inclusion disease virus or cytomegalovirus) for the developing human embryo. Some other investigators have also shown that CMV may be involved in different pathological conditions, that it is an ubiquous agent capable of producing a high incidence of infection, usually asymptomatic, under quite diverse ecological conditions, and that the proportion of individuals that have been in contact with the virus increases with age, which is evidenced by the frequency of seropositivity to the specific antigen. The high prevalence of CF antibodies to CMV in the studied groups from the state of Chiapas, particularly in Lacanj\u00e1 where 45% of the total population (120 inhabitants) was included in the survey, indicates a wide dissemination of this virus. Lower levels of seropositivity were found among children from the Mexico City group, but they are higher than those found in serological surveys in children from Huixquilucan (state of Mexico) and from Seattle and Dallas in U.S.A. The possible implications of some seroepidemiological characteristics of CMV infection are discussed."}
{"id": "PMID:202293", "title": "[Antiviral antibodies in acute laryngotracheobronchitis].", "content": "Antibodies to influenza A2, influenza B, parainfluenza 2 and 3, adenovirus and respiratory syncytial viruses were determined in thirty nine children with acute laryngotracheobronchitis; nine cases were not included in the analysis because of the presence of anticomplementary sera; 40% of cases were positive, 20% to influenza A2, 10% to influenza B (one case of double infection with influenza B and parainfluenza 2 viruses), 6.7% to respiratory syncytial virus and 3.3% to parainfluenza 2. Results are compared with previous studies done in Mexico.", "contents": "[Antiviral antibodies in acute laryngotracheobronchitis]. Antibodies to influenza A2, influenza B, parainfluenza 2 and 3, adenovirus and respiratory syncytial viruses were determined in thirty nine children with acute laryngotracheobronchitis; nine cases were not included in the analysis because of the presence of anticomplementary sera; 40% of cases were positive, 20% to influenza A2, 10% to influenza B (one case of double infection with influenza B and parainfluenza 2 viruses), 6.7% to respiratory syncytial virus and 3.3% to parainfluenza 2. Results are compared with previous studies done in Mexico."}
{"id": "PMID:202297", "title": "Biochemical markers in bronchial carcinoma.", "content": "A total of 107 patients with bronchial carcinoma have been studied for the presence of potential circulating tumour markers which might be used as indicators of recurrence after primary treatment. Plasma carcinoembryonic antigen (CEA) levels were estimated in every patient and, after a preliminary hormone screening study, plasma calcitonin (CT) and parathyroid hormone (PTH) levels were assayed in 66 patients. Oat-cell tumours proved to be of particular interest in that CEA levels greater than 40 microgram/l were measured (initially or subsequently) in 40.6 percent and CT levels were elevated in 75 percent. Longitudinal studies point towards the possible use of elevated marker levels as guides to therapy when all other features of recurrent disease are lacking. It is clear that no ideal tumour marker exists for bronchial carcinoma but in an individual case an abnormal level of one or more marker substances may provide a valuable aid to treatment.", "contents": "Biochemical markers in bronchial carcinoma. A total of 107 patients with bronchial carcinoma have been studied for the presence of potential circulating tumour markers which might be used as indicators of recurrence after primary treatment. Plasma carcinoembryonic antigen (CEA) levels were estimated in every patient and, after a preliminary hormone screening study, plasma calcitonin (CT) and parathyroid hormone (PTH) levels were assayed in 66 patients. Oat-cell tumours proved to be of particular interest in that CEA levels greater than 40 microgram/l were measured (initially or subsequently) in 40.6 percent and CT levels were elevated in 75 percent. Longitudinal studies point towards the possible use of elevated marker levels as guides to therapy when all other features of recurrent disease are lacking. It is clear that no ideal tumour marker exists for bronchial carcinoma but in an individual case an abnormal level of one or more marker substances may provide a valuable aid to treatment."}
{"id": "PMID:202298", "title": "Primary cancer of the liver in Kenyan children.", "content": "In 9 years in Kenya, 34 examples of primary liver cancer wer diagnosed in patients in the first two decades of life. This represents 4.7% of all liver cancers during this period. The larger proportion (29) were hepatocellular carcinoma. In the second decade, there was a notable association with macronodular cirrhosis. Analogy with experimental work suggests that cells in mitotic cycle may be more vulnerable to the effect of environmental carcinogens. Five examples of hepatoblastoma were identified at ages from 2 months to 14 years; none showed the features of \"mixed\" tumours. The ratio of hepatoblastoma to hepatocellular carcinoma was the reverse of that found in other large series of juvenile hepatic tumours. The histopathological features of these tumours are described and problems of their classification are discussed.", "contents": "Primary cancer of the liver in Kenyan children. In 9 years in Kenya, 34 examples of primary liver cancer wer diagnosed in patients in the first two decades of life. This represents 4.7% of all liver cancers during this period. The larger proportion (29) were hepatocellular carcinoma. In the second decade, there was a notable association with macronodular cirrhosis. Analogy with experimental work suggests that cells in mitotic cycle may be more vulnerable to the effect of environmental carcinogens. Five examples of hepatoblastoma were identified at ages from 2 months to 14 years; none showed the features of \"mixed\" tumours. The ratio of hepatoblastoma to hepatocellular carcinoma was the reverse of that found in other large series of juvenile hepatic tumours. The histopathological features of these tumours are described and problems of their classification are discussed."}
{"id": "PMID:202299", "title": "Biological activities of solubilized surface antigens of embryonic and polyoma-virus-transformed cells.", "content": "Various antigenic activities of polyoma virus-transformed and embryonic mouse cells were retained after 3M KCl solubilization of surface components. Particularly, transplantation antigen (TSTA) demonstrated by homograft rejection, and surface (S) antigen, detected by inhibition of immunofluorescence on polyoma-virus-transformed mouse cells, could be demonstrated. The crude soluble extracts were partially purified by salting out with (NH4)2SO4. In the case of polyoma-virus-transformed cells, TSTA and a part of S antigen activity were found in the same fraction (60% (NH4)2SO4 saturation) while another part of S antigen was salted out at 80% saturation. By chromatography, S antigen activity was found in 2 zones for transformed cells and in one zone for embryonic cells. One of these zones was common to both cell extracts.", "contents": "Biological activities of solubilized surface antigens of embryonic and polyoma-virus-transformed cells. Various antigenic activities of polyoma virus-transformed and embryonic mouse cells were retained after 3M KCl solubilization of surface components. Particularly, transplantation antigen (TSTA) demonstrated by homograft rejection, and surface (S) antigen, detected by inhibition of immunofluorescence on polyoma-virus-transformed mouse cells, could be demonstrated. The crude soluble extracts were partially purified by salting out with (NH4)2SO4. In the case of polyoma-virus-transformed cells, TSTA and a part of S antigen activity were found in the same fraction (60% (NH4)2SO4 saturation) while another part of S antigen was salted out at 80% saturation. By chromatography, S antigen activity was found in 2 zones for transformed cells and in one zone for embryonic cells. One of these zones was common to both cell extracts."}
{"id": "PMID:202294", "title": "[Epidemiological aspects of gastroenteritis dut to Rotavirus].", "content": "During December 1976 to January-March 1977, 13/53 children less than 5 years of age were admitted with acute enteritis caused by rotaviruses to the Hospital del Ni\u00f1o, DIF. There is already convincing evidence that this new virus will prove to be the most important etiological agent of sporadic acute enteritis in young children.", "contents": "[Epidemiological aspects of gastroenteritis dut to Rotavirus]. During December 1976 to January-March 1977, 13/53 children less than 5 years of age were admitted with acute enteritis caused by rotaviruses to the Hospital del Ni\u00f1o, DIF. There is already convincing evidence that this new virus will prove to be the most important etiological agent of sporadic acute enteritis in young children."}
{"id": "PMID:202300", "title": "Modulator protein as a component of the myosin light chain kinase from chicken gizzard.", "content": "The Ca2+-dependent regulation of smooth muscle actomyosin involves a myosin light chain kinase (ATP: myosin light chain phosphotransferase). It has been shown (Dabrowska, R., Aromatorio, D., Sherry, J.M.F., and Hartshorne, D.J. 1977, Biochem. Biophys. Res. Commun. 78, 1263) that the kinase is composed of two proteins of approximate molecular weights 105 000 and 17 000. In this communication it is demonstrated that the 17 000 component is the modulator protein. This conclusion is based on: (1) the identical behavior of the 17 000 kinase component and modulator protein in assays of actomyosin Mg2+-ATPase activity, phosphorylation of myosin, and phosphodiesterase activity, and, (2) the similarity of the 17 000 kinase component and the modulator protein with respect to amino acid composition, absorption spectrum, and electrophoresis in urea-polyacrylamide gels. It is shown also that the modulator protein from smooth muscle and troponin C are distinct proteins.", "contents": "Modulator protein as a component of the myosin light chain kinase from chicken gizzard. The Ca2+-dependent regulation of smooth muscle actomyosin involves a myosin light chain kinase (ATP: myosin light chain phosphotransferase). It has been shown (Dabrowska, R., Aromatorio, D., Sherry, J.M.F., and Hartshorne, D.J. 1977, Biochem. Biophys. Res. Commun. 78, 1263) that the kinase is composed of two proteins of approximate molecular weights 105 000 and 17 000. In this communication it is demonstrated that the 17 000 component is the modulator protein. This conclusion is based on: (1) the identical behavior of the 17 000 kinase component and modulator protein in assays of actomyosin Mg2+-ATPase activity, phosphorylation of myosin, and phosphodiesterase activity, and, (2) the similarity of the 17 000 kinase component and the modulator protein with respect to amino acid composition, absorption spectrum, and electrophoresis in urea-polyacrylamide gels. It is shown also that the modulator protein from smooth muscle and troponin C are distinct proteins."}
{"id": "PMID:202302", "title": "Escherichia coli uridine diphosphate galactose 4-epimerase: circular dichroism of the protein and protein bound dihydronicotinamide adenine dinucleotide.", "content": "The circular dichroism spectra of E. coli UDP-galactose-4-epimerase in its native (epimerase-NAD+) and reduced (epimerase-NADH.UMP) forms between 190 and 400 nm are presented. The reduced form exhibits a large positive circular dichroism band at 340 nm attributed to NADH in the complex. Relative to the small negative band exhibited at this wavelength by free NADH itself, the rotational strength of enzyme-bound NADH is some 50 times larger than that of free NADH, while the oscillator strengths and other special characteristics are similar. This enhancement reflects dissymetric interactions involving the 340-nm transition and is most consistent with the dihydropyridine ring of NADH being highly immobilized in the reduced complex. In the 200- to 230-nm region both enzyme forms exhibit a negative band at 220 nm and a negative shoulder at 208 nm. The ellipticities of the reduced form are minimally 7% greater at both band positions than those of the native form. The spectra are interpreted to indicate that conversion of the native to the reduced form is accompanied by an increase in alpha-helix structure at the expense of unordered structure.", "contents": "Escherichia coli uridine diphosphate galactose 4-epimerase: circular dichroism of the protein and protein bound dihydronicotinamide adenine dinucleotide. The circular dichroism spectra of E. coli UDP-galactose-4-epimerase in its native (epimerase-NAD+) and reduced (epimerase-NADH.UMP) forms between 190 and 400 nm are presented. The reduced form exhibits a large positive circular dichroism band at 340 nm attributed to NADH in the complex. Relative to the small negative band exhibited at this wavelength by free NADH itself, the rotational strength of enzyme-bound NADH is some 50 times larger than that of free NADH, while the oscillator strengths and other special characteristics are similar. This enhancement reflects dissymetric interactions involving the 340-nm transition and is most consistent with the dihydropyridine ring of NADH being highly immobilized in the reduced complex. In the 200- to 230-nm region both enzyme forms exhibit a negative band at 220 nm and a negative shoulder at 208 nm. The ellipticities of the reduced form are minimally 7% greater at both band positions than those of the native form. The spectra are interpreted to indicate that conversion of the native to the reduced form is accompanied by an increase in alpha-helix structure at the expense of unordered structure."}
{"id": "PMID:202304", "title": "EPR studies of higher plant mitochondria. I Ubisemiquinone and its relation to alternative respiratory oxidations.", "content": "An EPR investigation of the region of the higher plant respiratory chain involving ubiquinone and Center S-3 of succinate dehydrogenase is reported. At temperatures close to those of liquid helium, first derivative spectra corresponding to Center S-3 (gmax = 2.017) and a signal split around g = 2.00 (major features of peaks and troughs at g values of 2.045, 2.03, 1.985, 1.97 and 1.96) were observed in mung bean (Phaseolus aureus), Arum maculatum spadix, Sauromatum guttatum spadix and tulip bulb (Tulipa gesnerana) mitochondria. The split signal was small or absent in potato tuber and Symplocarpus foetidus spadix mitochondria. The redox behavior of these signals in mung bean mitochondria in a variety of respiratory steady-state conditions suggested that the components giving rise to them were an integral part of the respiratory chain and were located on the substrate side of coupling Site II. The split signal could be removed by addition of hydroxamic acids in all tissues tested, although the Ks of this effect was an order of magnitude higher than the Ki of inhibition of the alternative respiratory pathway in mung bean and Sauromatum guttatum spadix mitochondria. The results are discussed in relation to the current ideas on the ordering of components in the region around the classical Site II of the respiratory chain and in relation to the location of the alternative respiratory oxidase pathway of higher plants.", "contents": "EPR studies of higher plant mitochondria. I Ubisemiquinone and its relation to alternative respiratory oxidations. An EPR investigation of the region of the higher plant respiratory chain involving ubiquinone and Center S-3 of succinate dehydrogenase is reported. At temperatures close to those of liquid helium, first derivative spectra corresponding to Center S-3 (gmax = 2.017) and a signal split around g = 2.00 (major features of peaks and troughs at g values of 2.045, 2.03, 1.985, 1.97 and 1.96) were observed in mung bean (Phaseolus aureus), Arum maculatum spadix, Sauromatum guttatum spadix and tulip bulb (Tulipa gesnerana) mitochondria. The split signal was small or absent in potato tuber and Symplocarpus foetidus spadix mitochondria. The redox behavior of these signals in mung bean mitochondria in a variety of respiratory steady-state conditions suggested that the components giving rise to them were an integral part of the respiratory chain and were located on the substrate side of coupling Site II. The split signal could be removed by addition of hydroxamic acids in all tissues tested, although the Ks of this effect was an order of magnitude higher than the Ki of inhibition of the alternative respiratory pathway in mung bean and Sauromatum guttatum spadix mitochondria. The results are discussed in relation to the current ideas on the ordering of components in the region around the classical Site II of the respiratory chain and in relation to the location of the alternative respiratory oxidase pathway of higher plants."}
{"id": "PMID:202305", "title": "Mitochondrial respiratory chain of Tetrahymena pyriformis: the properties of submitochondrial particles and the soluble b and c type pigments.", "content": "Submitochondrial particles isolated from Tetrahymena pyriformis contain essentially the same redox carriers as those present in parental mitochondria: at pH 7.2 and 22 degree C there are two b-type pigments with half-reduction potentials of --0.04 and --0.17 V, a c-type cytochrome with a half reduction potential of 0.215 V, and a two-component cytochrome a2 with Em7.2 of 0.245 and 0.345 V. EPR spectra of the aerobic submitochondrial particles in the absence of substrate show the presence of low spine ferric hemes with g values at 3.4 and 3.0, a high spin ferric heme with g =6, and a g=2.0 signal characteristic of oxidized copper. In the reduced submitochondrial particles signals of various iron-sulfur centers are observed. Cytochrome c553 is lost from mitochondria during preparation of the submitochondrial particles. The partially purified cytochrome c553 is a negatively charged protein at neutral pH with an Em7.2 of 0.25 V which binds to the cytochrome c-depleted Tetrahymena mitochondria in the amount of 0.5 nmol/mg protein with KD of 0.8.10(-6) M. Reduced cytochrome c553 serves as an efficient substrate in the reaction with its own oxidase. The EPR spectrum of the partially purified cytochrome c553 shows the presence of a low spin ferric heme with the dominant resonance signal at g=3.28. A pigment with an alpha absorption maximum at 560 nm can be solubilized from the Tetrahymena cells with butanol. This pigments has a molecular weight of approx. 18 000, and Em7.2 of--0.17 V and exhibits a high spin ferric heme signal at g=6.", "contents": "Mitochondrial respiratory chain of Tetrahymena pyriformis: the properties of submitochondrial particles and the soluble b and c type pigments. Submitochondrial particles isolated from Tetrahymena pyriformis contain essentially the same redox carriers as those present in parental mitochondria: at pH 7.2 and 22 degree C there are two b-type pigments with half-reduction potentials of --0.04 and --0.17 V, a c-type cytochrome with a half reduction potential of 0.215 V, and a two-component cytochrome a2 with Em7.2 of 0.245 and 0.345 V. EPR spectra of the aerobic submitochondrial particles in the absence of substrate show the presence of low spine ferric hemes with g values at 3.4 and 3.0, a high spin ferric heme with g =6, and a g=2.0 signal characteristic of oxidized copper. In the reduced submitochondrial particles signals of various iron-sulfur centers are observed. Cytochrome c553 is lost from mitochondria during preparation of the submitochondrial particles. The partially purified cytochrome c553 is a negatively charged protein at neutral pH with an Em7.2 of 0.25 V which binds to the cytochrome c-depleted Tetrahymena mitochondria in the amount of 0.5 nmol/mg protein with KD of 0.8.10(-6) M. Reduced cytochrome c553 serves as an efficient substrate in the reaction with its own oxidase. The EPR spectrum of the partially purified cytochrome c553 shows the presence of a low spin ferric heme with the dominant resonance signal at g=3.28. A pigment with an alpha absorption maximum at 560 nm can be solubilized from the Tetrahymena cells with butanol. This pigments has a molecular weight of approx. 18 000, and Em7.2 of--0.17 V and exhibits a high spin ferric heme signal at g=6."}
{"id": "PMID:202308", "title": "Characterization of microsomal electron transport components from control, phenobarbital- and 3-methylcholanthrene-treated mice. II. Improved resolution and quantitation of major components in ammonium sulfate fractions from total liver microsomes.", "content": "Quantitation of microsomal components in ammonium sulfate fractions using a high-resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis system, and a comparison of these results with those from similar experiments on total liver microsomes has enabled us to identify and better characterize the interactions between microsomal electron transport components. It was found that: (1) phenobarbital decreased the amount of one protein component of approximately 50 000 molecular weight while increasing a component of very similar molecular weight; (2) only two proteins appeared to be associated with CO binding; (3) another protein of approximately 68 000 molecular weight, one of the glycoproteins found in liver microsomes, appears to be induced by phenobarbital pretreatment; (4) the induction of NADPH-cytochrome c reductase activity after phenobarbital pretreatment is not dependent on an increase in the known NADPH-dependent flavoprotein, but rather on the increase in some component found predominately in our most soluble sub-microsomal fraction. A very good separation of the above components was achieved by ammonium sulfate fractionation, e.g. simply on the basis of their solubility. This and the fact that the more-or-less soluble proteins were induced by phenobarbital or 3-methylcholanthrene respectively indicate that the solubility of membrane proteins plays a major role in the structure and function of microsomal membranes.", "contents": "Characterization of microsomal electron transport components from control, phenobarbital- and 3-methylcholanthrene-treated mice. II. Improved resolution and quantitation of major components in ammonium sulfate fractions from total liver microsomes. Quantitation of microsomal components in ammonium sulfate fractions using a high-resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis system, and a comparison of these results with those from similar experiments on total liver microsomes has enabled us to identify and better characterize the interactions between microsomal electron transport components. It was found that: (1) phenobarbital decreased the amount of one protein component of approximately 50 000 molecular weight while increasing a component of very similar molecular weight; (2) only two proteins appeared to be associated with CO binding; (3) another protein of approximately 68 000 molecular weight, one of the glycoproteins found in liver microsomes, appears to be induced by phenobarbital pretreatment; (4) the induction of NADPH-cytochrome c reductase activity after phenobarbital pretreatment is not dependent on an increase in the known NADPH-dependent flavoprotein, but rather on the increase in some component found predominately in our most soluble sub-microsomal fraction. A very good separation of the above components was achieved by ammonium sulfate fractionation, e.g. simply on the basis of their solubility. This and the fact that the more-or-less soluble proteins were induced by phenobarbital or 3-methylcholanthrene respectively indicate that the solubility of membrane proteins plays a major role in the structure and function of microsomal membranes."}
{"id": "PMID:202309", "title": "Phosphorylation of an actin.tropomyosin.troponin complex from human skeletal muscle.", "content": "A human skeletal actin.tropomyosin.troponin complex was phosphorylated in the presence of [gamma-32 P]ATP, Mg2+, adenosine 3':5'-monophosphate (cyclic AMP) and cyclic AMP-dependent protein kinase (protein kinase). Phosphorylation was not observed when the actin complex was incubated in the absence of protein kinase or 1 microM cyclic AMP. In the presence of 10(-7)  M Ca2+ and protein kinase 0.1 mole of [32P]phosphate per 196 000 g of protein was incorporated. This was two-fold higher than the [32P]phosphate content of a rabbit skeletal actin complex but two-fold lower than that of a bovine cardiac actin complex. At high Ca2+, 5.10(-5) M, little change in the phosphorylation of a human skeletal actin complex occurred. Phosphoserine and phosphothreonine were identified in the [32P]phosphorylated actin complex. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate showed that 60% of the label was associated with the tropomyosin binding component of troponin. The inhibitory component of troponin contained 16% of the bound [32P]phosphate. Increasing the Ca2+ concentration did not significantly decrease the [32P]phosphate content of the phosphorylated proteins in the actin complex. No change in the distribution of phosphoserine or phosphothreonine was observed. Half maximal calcium activation of the ATPase activity of reconstitute human skeletal actomyosin made with the [32P] phosphorylated human skeletal actin complex was the same as a reconstituted actomyosin made with an actin complex incubated in the absence of protein kinase at low or high Ca2+.", "contents": "Phosphorylation of an actin.tropomyosin.troponin complex from human skeletal muscle. A human skeletal actin.tropomyosin.troponin complex was phosphorylated in the presence of [gamma-32 P]ATP, Mg2+, adenosine 3':5'-monophosphate (cyclic AMP) and cyclic AMP-dependent protein kinase (protein kinase). Phosphorylation was not observed when the actin complex was incubated in the absence of protein kinase or 1 microM cyclic AMP. In the presence of 10(-7)  M Ca2+ and protein kinase 0.1 mole of [32P]phosphate per 196 000 g of protein was incorporated. This was two-fold higher than the [32P]phosphate content of a rabbit skeletal actin complex but two-fold lower than that of a bovine cardiac actin complex. At high Ca2+, 5.10(-5) M, little change in the phosphorylation of a human skeletal actin complex occurred. Phosphoserine and phosphothreonine were identified in the [32P]phosphorylated actin complex. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate showed that 60% of the label was associated with the tropomyosin binding component of troponin. The inhibitory component of troponin contained 16% of the bound [32P]phosphate. Increasing the Ca2+ concentration did not significantly decrease the [32P]phosphate content of the phosphorylated proteins in the actin complex. No change in the distribution of phosphoserine or phosphothreonine was observed. Half maximal calcium activation of the ATPase activity of reconstitute human skeletal actomyosin made with the [32P] phosphorylated human skeletal actin complex was the same as a reconstituted actomyosin made with an actin complex incubated in the absence of protein kinase at low or high Ca2+."}
{"id": "PMID:202310", "title": "Low-temperature flash photolysis studies of cytochrome oxidase and its environment.", "content": "The CO-binding kinetics of cytochrome a3, in isolated, detergent-solubilized cytochrome oxidase have been studied by flash photolysis over wide ranges of CO concentration and temperature. The results strongly suggest that CO has an intermediate bound state in its path to the final bound state at the heme iron. In the temperture range 230-273 K in frozen aqueous solutions, the recombination rates depend upon CO concentration; at low CO concentrations the kinetics are biphasic. The rate of the faster process depends upon the detergent concentration, that of the slower process upon the salt concentration. In addition, the faster process depends upon the amount of CO photodissociated. It is concluded that the cytochrome oxidase molecules are aggregated in regions that contain detergent and possibly some lipids. The regions retain considerable fluid character well below the macroscopic freezing point of the solution. The faster phase of the recombination is interpreted as the rebinding of CO molecules that remain in the fluid region after photodissociation. The slower phase would then be due to the migration of some dissociated CO out into surrounding frozen solvent. The non-Arrhenius behavior of both phase probably represents partial melting of the medium; preliminary NMR measurements of mobile protons support this hypothesis. Many of the kinetic features described here are also seen in mitochondria; thus the detergent-solubilized cytochrome oxidase may be a useful model system for the ligand-binding behavior of the enzyme in the mitochondrial membrane.", "contents": "Low-temperature flash photolysis studies of cytochrome oxidase and its environment. The CO-binding kinetics of cytochrome a3, in isolated, detergent-solubilized cytochrome oxidase have been studied by flash photolysis over wide ranges of CO concentration and temperature. The results strongly suggest that CO has an intermediate bound state in its path to the final bound state at the heme iron. In the temperture range 230-273 K in frozen aqueous solutions, the recombination rates depend upon CO concentration; at low CO concentrations the kinetics are biphasic. The rate of the faster process depends upon the detergent concentration, that of the slower process upon the salt concentration. In addition, the faster process depends upon the amount of CO photodissociated. It is concluded that the cytochrome oxidase molecules are aggregated in regions that contain detergent and possibly some lipids. The regions retain considerable fluid character well below the macroscopic freezing point of the solution. The faster phase of the recombination is interpreted as the rebinding of CO molecules that remain in the fluid region after photodissociation. The slower phase would then be due to the migration of some dissociated CO out into surrounding frozen solvent. The non-Arrhenius behavior of both phase probably represents partial melting of the medium; preliminary NMR measurements of mobile protons support this hypothesis. Many of the kinetic features described here are also seen in mitochondria; thus the detergent-solubilized cytochrome oxidase may be a useful model system for the ligand-binding behavior of the enzyme in the mitochondrial membrane."}
{"id": "PMID:202311", "title": "Single and multiple turnover reactions in the ubiquinone-cytochrome b-c2 oxidoreductase of Rhodopseudomonas sphaeroids: the physical chemistry of the major electron donor to cytochrome c2, and its coupled reactions.", "content": "We have examined the thermodynamic properties of the physiological electron donor to ferricytochrome c2 in chromatophores from the photosynthetic bacterium Rhodopseudomonas sphaeroides. This donor (Z), which is capable of reducing the ferricytochrome with a halftime of 1-2 ms under optimal conditions, has an oxidation-reduction midpoint potential of close to 150 mV at pH 7.0, and apparently requires two electrons and two protons for its equilibrium reduction. The state of reduction of Z, which may be a quinone.protein complex near the inner (cytochrome c2) side of the membrane, appears to govern the rate at which the cyclic photosynthetic electron transport system can operate. If Z is oxidized prior to the flash-oxidation of cytochrome c2, the re-reduction of the cytochrome takes hundreds of milliseconds and no third phase of the carotenoid bandshift occurs. In contrast if Z is reduced before flash activation, the cytochrome is rereduced within milliseconds and the third phase of the carotenoid bandshift occurs. The prior reduction of Z also has a dramatic effect on the uncoupler sensitivity of the rate of electron flow; if it is oxidized prior to activation, uncoupler can stimulate the cytochrome rereduction after several turnovers by less than tenfold, but if it is reduced prior to activation, the stimulation after several turnovers can be as dramatic as a thousandfold. The results suggest that Z plays a central role in controlling electron and proton movements in the ubiquinone cytochrome b-c2 oxido-reductase.", "contents": "Single and multiple turnover reactions in the ubiquinone-cytochrome b-c2 oxidoreductase of Rhodopseudomonas sphaeroids: the physical chemistry of the major electron donor to cytochrome c2, and its coupled reactions. We have examined the thermodynamic properties of the physiological electron donor to ferricytochrome c2 in chromatophores from the photosynthetic bacterium Rhodopseudomonas sphaeroides. This donor (Z), which is capable of reducing the ferricytochrome with a halftime of 1-2 ms under optimal conditions, has an oxidation-reduction midpoint potential of close to 150 mV at pH 7.0, and apparently requires two electrons and two protons for its equilibrium reduction. The state of reduction of Z, which may be a quinone.protein complex near the inner (cytochrome c2) side of the membrane, appears to govern the rate at which the cyclic photosynthetic electron transport system can operate. If Z is oxidized prior to the flash-oxidation of cytochrome c2, the re-reduction of the cytochrome takes hundreds of milliseconds and no third phase of the carotenoid bandshift occurs. In contrast if Z is reduced before flash activation, the cytochrome is rereduced within milliseconds and the third phase of the carotenoid bandshift occurs. The prior reduction of Z also has a dramatic effect on the uncoupler sensitivity of the rate of electron flow; if it is oxidized prior to activation, uncoupler can stimulate the cytochrome rereduction after several turnovers by less than tenfold, but if it is reduced prior to activation, the stimulation after several turnovers can be as dramatic as a thousandfold. The results suggest that Z plays a central role in controlling electron and proton movements in the ubiquinone cytochrome b-c2 oxido-reductase."}
{"id": "PMID:202312", "title": "The operation of the malate-aspartate shuttle in the reoxidation of glycolytic NADH in slices of fetal rat liver.", "content": "Lactate production by liver slices from fetal rats (17th--18th day of gestation) is enhanced about two fold by aminooxyacetate, an inhibitor of aspartate transaminase (EC 2.6.1.1). Such an effect is consistent with an increase of the cytosolic NAD-redox state owing to the parallel fall in the pyruvate level, whereas the glycolytic flux does not seem to be influenced appreciably. Indeed, although the inhibitor causes a marked increase of fructose 1,6-diphosphate, glucose-6-phosphate decreases only slightly. These results suggest that in fetal rat liver the malate-aspartate shuttle is operative in the reoxidation of cytosolic NADH produced during aerobic glycolysis.", "contents": "The operation of the malate-aspartate shuttle in the reoxidation of glycolytic NADH in slices of fetal rat liver. Lactate production by liver slices from fetal rats (17th--18th day of gestation) is enhanced about two fold by aminooxyacetate, an inhibitor of aspartate transaminase (EC 2.6.1.1). Such an effect is consistent with an increase of the cytosolic NAD-redox state owing to the parallel fall in the pyruvate level, whereas the glycolytic flux does not seem to be influenced appreciably. Indeed, although the inhibitor causes a marked increase of fructose 1,6-diphosphate, glucose-6-phosphate decreases only slightly. These results suggest that in fetal rat liver the malate-aspartate shuttle is operative in the reoxidation of cytosolic NADH produced during aerobic glycolysis."}
{"id": "PMID:202313", "title": "Redox potentials in hydro-organic media at normal and subzero temperatures. Ferro-ferricyanide and cytochrome c as models.", "content": "Redox potentials of ferro-ferricyanide and cytochrome c were measured in water/ethylene glycol and water/dimethylsulfoxide (volume ratio from 100/0 to 50/50) between 25 and -25 degrees C. For both systems, the midpoint potential decreases in the presence of organic solvents and increases by cooling. The magnitude of these variations is larger in dimethylsulfoxide than in ethylene glycol; moreover in the same solvent mixture it is larger with ferro-ferricyanide than with cytochrome c, so that the difference between the redox potentials of these two systems can be strongly affected and even reversed. While in pure water (cacodylate buffer pH 7.0, NaCl 0.1 M) they are respectively +388 and +265 mV, in 50% dimethylsulfoxide at 25 degrees C they decrease to +112 and +208 mV. Reduction of cytochrome c by ferro-ferricyanide, in this mixture, is then expected and was indeed observed. On the other hand, as (deltaE/deltaT)T, (E being the redox potential) is higher for ferro-ferricyanide than for cytochrome c, the oxidative power of the former for the latter is expected to increase as temperature decreases. This effect was observed in 50% ethylene glycol at -16 degrees C. Organic solvents and large temperature variations appear then as powerful perturbants of redox reactions. Their effects should be taken into account in studies of redox reactions carried out in cooled hydro-organic media.", "contents": "Redox potentials in hydro-organic media at normal and subzero temperatures. Ferro-ferricyanide and cytochrome c as models. Redox potentials of ferro-ferricyanide and cytochrome c were measured in water/ethylene glycol and water/dimethylsulfoxide (volume ratio from 100/0 to 50/50) between 25 and -25 degrees C. For both systems, the midpoint potential decreases in the presence of organic solvents and increases by cooling. The magnitude of these variations is larger in dimethylsulfoxide than in ethylene glycol; moreover in the same solvent mixture it is larger with ferro-ferricyanide than with cytochrome c, so that the difference between the redox potentials of these two systems can be strongly affected and even reversed. While in pure water (cacodylate buffer pH 7.0, NaCl 0.1 M) they are respectively +388 and +265 mV, in 50% dimethylsulfoxide at 25 degrees C they decrease to +112 and +208 mV. Reduction of cytochrome c by ferro-ferricyanide, in this mixture, is then expected and was indeed observed. On the other hand, as (deltaE/deltaT)T, (E being the redox potential) is higher for ferro-ferricyanide than for cytochrome c, the oxidative power of the former for the latter is expected to increase as temperature decreases. This effect was observed in 50% ethylene glycol at -16 degrees C. Organic solvents and large temperature variations appear then as powerful perturbants of redox reactions. Their effects should be taken into account in studies of redox reactions carried out in cooled hydro-organic media."}
{"id": "PMID:202314", "title": "The structure of a cytochrome oxidase-lipid model membrane.", "content": "The structure of \"membranous cytochrome oxidase\" has been investigated by X-ray diffraction, optical polarization spectroscopy and EPR spectroscopy. These studies indicate that the cytochrome oxidase molecules are oriented symmetrically in the membrane profile with a significant portion of their mass occurring within the extravesicular surface of the membrane; the oxidase molecultes span the membrane profile; the distribution of the oxidase molecules over the plane of these membranes is non-crystalline; the oxidase molecules contain bundles of alpha-helical polypeptide chain segments where the average orientation of the helices is normal to the membrane plane; and the average heme orientation within the oxidase molecules is such that the normal to the heme plane lies in the plane of the membrane.", "contents": "The structure of a cytochrome oxidase-lipid model membrane. The structure of \"membranous cytochrome oxidase\" has been investigated by X-ray diffraction, optical polarization spectroscopy and EPR spectroscopy. These studies indicate that the cytochrome oxidase molecules are oriented symmetrically in the membrane profile with a significant portion of their mass occurring within the extravesicular surface of the membrane; the oxidase molecultes span the membrane profile; the distribution of the oxidase molecules over the plane of these membranes is non-crystalline; the oxidase molecules contain bundles of alpha-helical polypeptide chain segments where the average orientation of the helices is normal to the membrane plane; and the average heme orientation within the oxidase molecules is such that the normal to the heme plane lies in the plane of the membrane."}
{"id": "PMID:202315", "title": "Studies on the orientations of the mitochondrial redox carriers. I. Orientation of the hemes of cytochrome c oxidase with respect to the plane of a cytochrome oxidase-lipid model membrane.", "content": "The liganded derivatives of mitochondrial cytochrome c oxidase have been prepared in hydrated oriented multilayers of membranous cytochrome c oxidase. The optical spectra of the liganded derivatives recorded at an angle of 45 degrees between the incident light beam and the normal to the planes of the membranes in the multilayers show dichroic ratios of almost 2 in the visible region and 1.2-1.4 in the Soret region. The dichroic ratios were found to be similar for both cytochromes a and a3. Electron paramagnetic resonance spectra of the azide, sulfide, and formate complexes of cytochrome c oxidase obtained as a function of the orientation of the applied magnetic field relative to the planes of the membranes in the multilayer confirm the optical data and demonstrate that both hemes of cytochrome c oxidase are oriented such that the angle between the heme normal and the membrane normal is approximately 90 degrees.", "contents": "Studies on the orientations of the mitochondrial redox carriers. I. Orientation of the hemes of cytochrome c oxidase with respect to the plane of a cytochrome oxidase-lipid model membrane. The liganded derivatives of mitochondrial cytochrome c oxidase have been prepared in hydrated oriented multilayers of membranous cytochrome c oxidase. The optical spectra of the liganded derivatives recorded at an angle of 45 degrees between the incident light beam and the normal to the planes of the membranes in the multilayers show dichroic ratios of almost 2 in the visible region and 1.2-1.4 in the Soret region. The dichroic ratios were found to be similar for both cytochromes a and a3. Electron paramagnetic resonance spectra of the azide, sulfide, and formate complexes of cytochrome c oxidase obtained as a function of the orientation of the applied magnetic field relative to the planes of the membranes in the multilayer confirm the optical data and demonstrate that both hemes of cytochrome c oxidase are oriented such that the angle between the heme normal and the membrane normal is approximately 90 degrees."}
{"id": "PMID:202316", "title": "Studies on the orientations of the mitochondrial redox carriers. II. Orientation of the mitochondrial chromophores with respect to the plane of the membrane in hydrated, oriented mitochondrial multilayers.", "content": "Orientations of the active site chromophores of the mitochondrial redox carriers have been investigated in hydrated, oriented multilayers of mitochondrial membranes using optical and EPR spectroscopy. The hemes of cytochrome c oxidase, cytochrome c1, and cytochromes b were found to be oriented in a similar manner, with the normal to their heme planes lying approximately in the plane of the mitochondrial membrane. The heme of cytochrome c was either less oriented in general or was oriented at an angle closer to the plane of the mitochondrial membrane than were the hemes of the \"tightly bound\" mitochondrial cytochromes. EPR spectra of the azide, sulfide and formate complexes of cytochrome c oxidase in mitochondria in situ obtained as a function of the orientation of the applied magnetic field relative to the planes of the membrane multilayers showed that both hemes of the oxidase were oriented in such a way that the angle between the heme normal and the membrane normal was approx. 90 degrees.", "contents": "Studies on the orientations of the mitochondrial redox carriers. II. Orientation of the mitochondrial chromophores with respect to the plane of the membrane in hydrated, oriented mitochondrial multilayers. Orientations of the active site chromophores of the mitochondrial redox carriers have been investigated in hydrated, oriented multilayers of mitochondrial membranes using optical and EPR spectroscopy. The hemes of cytochrome c oxidase, cytochrome c1, and cytochromes b were found to be oriented in a similar manner, with the normal to their heme planes lying approximately in the plane of the mitochondrial membrane. The heme of cytochrome c was either less oriented in general or was oriented at an angle closer to the plane of the mitochondrial membrane than were the hemes of the \"tightly bound\" mitochondrial cytochromes. EPR spectra of the azide, sulfide and formate complexes of cytochrome c oxidase in mitochondria in situ obtained as a function of the orientation of the applied magnetic field relative to the planes of the membrane multilayers showed that both hemes of the oxidase were oriented in such a way that the angle between the heme normal and the membrane normal was approx. 90 degrees."}
{"id": "PMID:202317", "title": "The role of plastidic cytochrome c in algal electron transport and photophosphorylation.", "content": "By an improved isolation procedure chloroplasts could be obtained from the alga Bumilleriopsis filiformis (Xanthophyceae) which exhibited high electron transport rates tightly coupled to ATP formation. Uncouplers both stimulate electron transport and inhibit photophosphorylation. These chloroplasts retain almost all soluble cytochrome c-553 besides a membrane-bound cytochrome c-554.5 (=f-554.5). Sonification or iron deficiency removed the soluble cytochrome only with a concurrent decrease of electron transport from water to methyl viologen or to NADP and decreased non-cyclic and cyclic photophosphorylation. However, photosynthetic control and the P/2e ratios remain unaltered. In Bumilleriopsis, which apparently has no plastocyanin, the soluble cytochrome c-553 seemingly links electron transport between the bound cytochrome c and P-700.", "contents": "The role of plastidic cytochrome c in algal electron transport and photophosphorylation. By an improved isolation procedure chloroplasts could be obtained from the alga Bumilleriopsis filiformis (Xanthophyceae) which exhibited high electron transport rates tightly coupled to ATP formation. Uncouplers both stimulate electron transport and inhibit photophosphorylation. These chloroplasts retain almost all soluble cytochrome c-553 besides a membrane-bound cytochrome c-554.5 (=f-554.5). Sonification or iron deficiency removed the soluble cytochrome only with a concurrent decrease of electron transport from water to methyl viologen or to NADP and decreased non-cyclic and cyclic photophosphorylation. However, photosynthetic control and the P/2e ratios remain unaltered. In Bumilleriopsis, which apparently has no plastocyanin, the soluble cytochrome c-553 seemingly links electron transport between the bound cytochrome c and P-700."}
{"id": "PMID:202318", "title": "Spin-labeling of Escherichia coli membrane by enzymatic synthesis of phosphatidylglycerol and divalent cation-induced interaction of phosphatidylglycerol with membrane proteins.", "content": "Escherichia coli membrane particulate fraction has been spin-labeled by incubating with sn-glycerol-3-phosphate, CTP, palmitoyl CoA and 12-nitroxide stearoyl CoA. Incorporation of the spin-labeled acyl chain into phosphatidyl-glycerol was confirmed. ESR spectrum of the spin-labeled phosphatidylglycerol in E. coli membrane consisted at least of two components; one due to the labels undergoing rapid anisotropic motions and the other due to strongly immobilized labels (the overall splitting value, approx. 58 G). The relative intensity of the two components was dependent on the concentration of divalent cations. The immobilized component decreased on treatment of the membrane with EDTA and increased on addition of Mg2+ or Ca2+. The spectrum at 1 mM Mg2+ or Ca2+ consisted almost only of the immobilized component. Spin-labeled phosphatidylglycerol in total lipid membrane showed ESR spectrum due to mobile labels and the spectrum was not affected appreciably by the divalent cations. The results suggest the divalent cation-mediated interaction of phosphatidylglycerol with proteins in E. coli membrane. Phosphoenolpyruvate-dependent uptake of methyl-alpha-D-glucoside was markedly accelerated by Mg2+. Ca2+ was not effective for the enhancement. The divalent cation-induced interaction of phosphatidylglycerol with proteins was discussed in relation to the sugar transport.", "contents": "Spin-labeling of Escherichia coli membrane by enzymatic synthesis of phosphatidylglycerol and divalent cation-induced interaction of phosphatidylglycerol with membrane proteins. Escherichia coli membrane particulate fraction has been spin-labeled by incubating with sn-glycerol-3-phosphate, CTP, palmitoyl CoA and 12-nitroxide stearoyl CoA. Incorporation of the spin-labeled acyl chain into phosphatidyl-glycerol was confirmed. ESR spectrum of the spin-labeled phosphatidylglycerol in E. coli membrane consisted at least of two components; one due to the labels undergoing rapid anisotropic motions and the other due to strongly immobilized labels (the overall splitting value, approx. 58 G). The relative intensity of the two components was dependent on the concentration of divalent cations. The immobilized component decreased on treatment of the membrane with EDTA and increased on addition of Mg2+ or Ca2+. The spectrum at 1 mM Mg2+ or Ca2+ consisted almost only of the immobilized component. Spin-labeled phosphatidylglycerol in total lipid membrane showed ESR spectrum due to mobile labels and the spectrum was not affected appreciably by the divalent cations. The results suggest the divalent cation-mediated interaction of phosphatidylglycerol with proteins in E. coli membrane. Phosphoenolpyruvate-dependent uptake of methyl-alpha-D-glucoside was markedly accelerated by Mg2+. Ca2+ was not effective for the enhancement. The divalent cation-induced interaction of phosphatidylglycerol with proteins was discussed in relation to the sugar transport."}
{"id": "PMID:202319", "title": "Studies on the regulatory properties of chloroplast fructose-1,6-bisphosphatase.", "content": "The regulatory properties of chloroplast fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, (EC 3.1.3.11) were examined with a homogeneous enzyme preparation isolated from spinach leaves. The activation of the enzyme, that was earlier shown to occur via reduced thioredoxin, was found to be accompanied by a structural change that took place more slowly than the rate of catalysis. The recently found deactivation of the thioredoxin-activated enzyme by physiological oxidants such as oxidized glutathione and dehydroascorbic acid was also slow relative to catalysis. Under the conditions used, the activated enzyme showed a pH optimum of about 8.0, whereas the corresponding value for the non-activated form was pH 8.8. The importance of the thioredoxin-linked mechanism of enzyme regulation that is effected through photoreduced ferredoxin and ferredoxin-thioredoxin reductase is discussed in relation to other light-controlled regulatory agents in chloroplasts.", "contents": "Studies on the regulatory properties of chloroplast fructose-1,6-bisphosphatase. The regulatory properties of chloroplast fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, (EC 3.1.3.11) were examined with a homogeneous enzyme preparation isolated from spinach leaves. The activation of the enzyme, that was earlier shown to occur via reduced thioredoxin, was found to be accompanied by a structural change that took place more slowly than the rate of catalysis. The recently found deactivation of the thioredoxin-activated enzyme by physiological oxidants such as oxidized glutathione and dehydroascorbic acid was also slow relative to catalysis. Under the conditions used, the activated enzyme showed a pH optimum of about 8.0, whereas the corresponding value for the non-activated form was pH 8.8. The importance of the thioredoxin-linked mechanism of enzyme regulation that is effected through photoreduced ferredoxin and ferredoxin-thioredoxin reductase is discussed in relation to other light-controlled regulatory agents in chloroplasts."}
{"id": "PMID:202320", "title": "Evidence for the non-identity of proteins having synthase phosphatase, phosphorylase phosphatase and histone phosphatase activity in rat liver.", "content": "Synthase phosphatase, phosphorylase phosphatase and histone phosphatase in rat liver were measured using as substrates purified liver synthase D, phosphorylase alpha and 32P-labelled phosphorylated f1 histone, respectively. The three phosphatase enzymes had different sedimentation characteristics. Both synthase phosphatase and phosphorylase phosphatase were found to sediment with the microsomal fraction under our experimental conditions. Only 10% of histone phosphatase was in this fraction; the majority was in the cytosol. No change in histone phosphatase was observed in the adrenalectomized fasted rat whereas synthase phosphatase and phosphorylase phosphatase activities were decreased 5-10 fold. Fractionation of liver extract with ethanol produced a dissociation of the three phosphatase activities. When a partially purified fraction was put on a DEAE-cellulose column, synthase phosphatase and phosphorylase phosphatase both exhibited broad elution profiles but their activity peaks did not coincide. Histone phosphatase eluted as a single discrete peak. When the supernatant of CaCl2-treated microsomal fraction was put on a Sepharose 4B column, the majority of synthase phosphatase was found to elute with the larger molecular weight proteins whereas the majority of phosphorylase phosphatase eluted with the smaller species. Histone phosphatase migrated as a single peak and was of intermediate size. Synthase phosphorylase phosphatase by synthase D (Ki approximately 2 units/ml). The inhibition of synthase phosphatase by phosphorylase alpha was kinetically non-competitive with substrate. Histone phosphatase activity was not inhibited by synthase D or by phosphorylase alpha. The above results suggest that different proteins are involved in the dephosphorylation of synthase D, phosphorylase alpha and histone in the cell.", "contents": "Evidence for the non-identity of proteins having synthase phosphatase, phosphorylase phosphatase and histone phosphatase activity in rat liver. Synthase phosphatase, phosphorylase phosphatase and histone phosphatase in rat liver were measured using as substrates purified liver synthase D, phosphorylase alpha and 32P-labelled phosphorylated f1 histone, respectively. The three phosphatase enzymes had different sedimentation characteristics. Both synthase phosphatase and phosphorylase phosphatase were found to sediment with the microsomal fraction under our experimental conditions. Only 10% of histone phosphatase was in this fraction; the majority was in the cytosol. No change in histone phosphatase was observed in the adrenalectomized fasted rat whereas synthase phosphatase and phosphorylase phosphatase activities were decreased 5-10 fold. Fractionation of liver extract with ethanol produced a dissociation of the three phosphatase activities. When a partially purified fraction was put on a DEAE-cellulose column, synthase phosphatase and phosphorylase phosphatase both exhibited broad elution profiles but their activity peaks did not coincide. Histone phosphatase eluted as a single discrete peak. When the supernatant of CaCl2-treated microsomal fraction was put on a Sepharose 4B column, the majority of synthase phosphatase was found to elute with the larger molecular weight proteins whereas the majority of phosphorylase phosphatase eluted with the smaller species. Histone phosphatase migrated as a single peak and was of intermediate size. Synthase phosphorylase phosphatase by synthase D (Ki approximately 2 units/ml). The inhibition of synthase phosphatase by phosphorylase alpha was kinetically non-competitive with substrate. Histone phosphatase activity was not inhibited by synthase D or by phosphorylase alpha. The above results suggest that different proteins are involved in the dephosphorylation of synthase D, phosphorylase alpha and histone in the cell."}
{"id": "PMID:202321", "title": "Effects of zinc chloride on the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart.", "content": "In the presence of 10 micrometer Ca2+ and 5 mM Mg2+ (or 0.25 mM Mg2+), the addition of 100 micrometer Zn2+, Ni2+, Co2+, Fe2+, Cu2+ or 1 mM Mn2+ resulted in varying degrees of stimulation or inhibition of 10(-6) M cyclic GMP and cyclic AMP hydrolysis by the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart in the absence or presence of phosphodiesterase activator. The substrate specificity of the enzyme was altered under several conditions. The addition of Zn2+ in the presence of 5 mM Mg2+ and the absence of activator resulted in the stimulation of cyclic GMP hydrolysis over a narrow substrate range while reducing the V 65% due to a shift in the kinetics from non-linear with Mg2+ alone to linear in the presence of Zn2+ and Mg2+. Zn2+ inhibited the hydrolysis of cyclic GMP and cyclic AMP in the presence of activator with Ki values of 70 and 100 micrometer, respectively. Zn2+ inhibition was non-competitive with substrate, activator and Ca2+ but was competitive with Mg2+. In the presence of 10 micrometer Ca2+ and activator, a Ki of 15 micrometer for Zn2+ vs. Mg2+ was noted in the hydrolysis of 10(-6) M cyclic GMP. Several effects of Zn2+ are discussed which have been noted in other studies and might be due in part to changes in cyclic nucleotide levels following phosphodiesterase inhibition.", "contents": "Effects of zinc chloride on the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart. In the presence of 10 micrometer Ca2+ and 5 mM Mg2+ (or 0.25 mM Mg2+), the addition of 100 micrometer Zn2+, Ni2+, Co2+, Fe2+, Cu2+ or 1 mM Mn2+ resulted in varying degrees of stimulation or inhibition of 10(-6) M cyclic GMP and cyclic AMP hydrolysis by the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart in the absence or presence of phosphodiesterase activator. The substrate specificity of the enzyme was altered under several conditions. The addition of Zn2+ in the presence of 5 mM Mg2+ and the absence of activator resulted in the stimulation of cyclic GMP hydrolysis over a narrow substrate range while reducing the V 65% due to a shift in the kinetics from non-linear with Mg2+ alone to linear in the presence of Zn2+ and Mg2+. Zn2+ inhibited the hydrolysis of cyclic GMP and cyclic AMP in the presence of activator with Ki values of 70 and 100 micrometer, respectively. Zn2+ inhibition was non-competitive with substrate, activator and Ca2+ but was competitive with Mg2+. In the presence of 10 micrometer Ca2+ and activator, a Ki of 15 micrometer for Zn2+ vs. Mg2+ was noted in the hydrolysis of 10(-6) M cyclic GMP. Several effects of Zn2+ are discussed which have been noted in other studies and might be due in part to changes in cyclic nucleotide levels following phosphodiesterase inhibition."}
{"id": "PMID:202322", "title": "Subunit structure of Achromobacter collagenase.", "content": "The highly active form of collagenase (EC 3.4.24.3) from Achromobacter iophagus (specific activity 2 microkat/mg) has a molecular weight of 70,000 and the sedimentation coefficient s20,2 = 4.4 S. It is composed of two subunits of molecular weight 35,000 and s20,w of 2.9 S. The dissociation of the dimer under different conditions resulted in the complete and irreversible loss of enzymic activity. A unique N-terminal sequence Thr-Ala-Ala-Asp-Leu-Glu-Ala-Leu-Val- indicates that the two subunits are identical, at least in the N-terminal part of the polypeptide chain. Reduction and pyridylethylation of the subunit change neither molecular weight nor amino acid composition: therefore each subunit of molecular weight 35,000 consists of a single polypeptide chain. Another active and homogeneous form of Achromobacter collagenase (specific activity 1.64 microkat/mg) gives a value for the apparent molecular weight of 80,000 on sodium dodecyl sulphate-polyacrylamide electrophoresis. It is also a dimer in which each of the two subunits of molecular weight 35,000 binds non-covalently a peptide of molecular weight 5000. The dissociation of this form of collagenase is also accompanied by irreversible loss of enzymic activity. The amino acid composition of the subunits which were isolated from both 70,000 and 80,000 collagenases is the same. The role of dimer-monometer equilibrium in the biological function of collagenase is discussed.", "contents": "Subunit structure of Achromobacter collagenase. The highly active form of collagenase (EC 3.4.24.3) from Achromobacter iophagus (specific activity 2 microkat/mg) has a molecular weight of 70,000 and the sedimentation coefficient s20,2 = 4.4 S. It is composed of two subunits of molecular weight 35,000 and s20,w of 2.9 S. The dissociation of the dimer under different conditions resulted in the complete and irreversible loss of enzymic activity. A unique N-terminal sequence Thr-Ala-Ala-Asp-Leu-Glu-Ala-Leu-Val- indicates that the two subunits are identical, at least in the N-terminal part of the polypeptide chain. Reduction and pyridylethylation of the subunit change neither molecular weight nor amino acid composition: therefore each subunit of molecular weight 35,000 consists of a single polypeptide chain. Another active and homogeneous form of Achromobacter collagenase (specific activity 1.64 microkat/mg) gives a value for the apparent molecular weight of 80,000 on sodium dodecyl sulphate-polyacrylamide electrophoresis. It is also a dimer in which each of the two subunits of molecular weight 35,000 binds non-covalently a peptide of molecular weight 5000. The dissociation of this form of collagenase is also accompanied by irreversible loss of enzymic activity. The amino acid composition of the subunits which were isolated from both 70,000 and 80,000 collagenases is the same. The role of dimer-monometer equilibrium in the biological function of collagenase is discussed."}
{"id": "PMID:202324", "title": "Purification and properties of NAD+-dependent glyceraldehyde-3-phosphate dehydrogenase from spinach leaves.", "content": "An NAD+-dependent glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC. 1.2.1.12) has been purified from spinach leaves as a homogeneous protein of 150,000 daltons. Kinetic constants of 2.5 . 10(-4) M and 4 . 10(-4) M have been calculated for NAD+ and glyceraldehyde-3-phosphate, respectively. The amino acid composition is characterized by a cysteine content higher than that found in analogous enzymes. On sodium dodecyl sulphate gel electrophoresis, the native enzyme dissociates into two subunits of 37,000 and 14,000 daltons. The two subunits have been isolated in equimolar amounts by gel filtration; end-group analysis shows that alanine is the N-terminal residue of the large subunit, while serine is found at the N-terminus of the small subunit. Comparison of amino acid analysies and peptide maps shows that the two subunits have a different amino acid sequence. These results indicate that the NAD+-dependent glyceraldehyde-3-phosphate, dehydrogenase, isolated from spinach leaves has an atypical oligomeric structure, the protomer being formed by two different subunits.", "contents": "Purification and properties of NAD+-dependent glyceraldehyde-3-phosphate dehydrogenase from spinach leaves. An NAD+-dependent glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC. 1.2.1.12) has been purified from spinach leaves as a homogeneous protein of 150,000 daltons. Kinetic constants of 2.5 . 10(-4) M and 4 . 10(-4) M have been calculated for NAD+ and glyceraldehyde-3-phosphate, respectively. The amino acid composition is characterized by a cysteine content higher than that found in analogous enzymes. On sodium dodecyl sulphate gel electrophoresis, the native enzyme dissociates into two subunits of 37,000 and 14,000 daltons. The two subunits have been isolated in equimolar amounts by gel filtration; end-group analysis shows that alanine is the N-terminal residue of the large subunit, while serine is found at the N-terminus of the small subunit. Comparison of amino acid analysies and peptide maps shows that the two subunits have a different amino acid sequence. These results indicate that the NAD+-dependent glyceraldehyde-3-phosphate, dehydrogenase, isolated from spinach leaves has an atypical oligomeric structure, the protomer being formed by two different subunits."}
{"id": "PMID:202326", "title": "Incorporation of excess cholesterol by high density serum lipoproteins.", "content": "Excess cholesterol was added to human HDL3 and to bovine mammalian high density serum lipoprotein (HDL) by incubating aqueous lipoprotein solutions with solid dispersions of [4-(14)C]cholesterol on Celite. Lipoprotein cholesterol complexes were isolated by centrifugation and filtration through a Sepharose 4B column. The pure complexes were analyzed for protein and lipid content and composition and were subsequently investigated by physical methods (analytical ultracentrifugation, circular dichroism, and fluorescence spectroscopy), in order to detect any structural changes induced by added cholesterol. The rates of cholesterol uptake varied as an inverse function of the intrinsic cholesterol present in the native lipoproteins. The maximum cholesterol taken up by human HDL3 increased the free cholesterol content from 3--4% (initial) up to 22% of the total lipoprotein weight. Bovine HDL was observed to increase its free cholesterol content from 2--4% (initial) up to 11--17% of the total lipoprotein weight, before denaturation. At maximum levels of added cholesterol, both lipoproteins had increased molecular weights and sedimentation velocity coefficients corresponding to the increased mass of the particles. No major changes in the hydrodynamic properties were observed. At the molecular level, the protein components only showed a 15--20% decrease in fluorescence intensity, possibly a consequence of a modified environment of the aromatic amino acid residues. In the human HDL3, added cholesterol increased the microviscosity of the lipid domains by 1.2 P at 25 degrees C (from 3.4 to 4.6 P), but did not affect the fluidity of bovine HDL lipids (5.9 P).", "contents": "Incorporation of excess cholesterol by high density serum lipoproteins. Excess cholesterol was added to human HDL3 and to bovine mammalian high density serum lipoprotein (HDL) by incubating aqueous lipoprotein solutions with solid dispersions of [4-(14)C]cholesterol on Celite. Lipoprotein cholesterol complexes were isolated by centrifugation and filtration through a Sepharose 4B column. The pure complexes were analyzed for protein and lipid content and composition and were subsequently investigated by physical methods (analytical ultracentrifugation, circular dichroism, and fluorescence spectroscopy), in order to detect any structural changes induced by added cholesterol. The rates of cholesterol uptake varied as an inverse function of the intrinsic cholesterol present in the native lipoproteins. The maximum cholesterol taken up by human HDL3 increased the free cholesterol content from 3--4% (initial) up to 22% of the total lipoprotein weight. Bovine HDL was observed to increase its free cholesterol content from 2--4% (initial) up to 11--17% of the total lipoprotein weight, before denaturation. At maximum levels of added cholesterol, both lipoproteins had increased molecular weights and sedimentation velocity coefficients corresponding to the increased mass of the particles. No major changes in the hydrodynamic properties were observed. At the molecular level, the protein components only showed a 15--20% decrease in fluorescence intensity, possibly a consequence of a modified environment of the aromatic amino acid residues. In the human HDL3, added cholesterol increased the microviscosity of the lipid domains by 1.2 P at 25 degrees C (from 3.4 to 4.6 P), but did not affect the fluidity of bovine HDL lipids (5.9 P)."}
{"id": "PMID:202327", "title": "The effect of quaternary structure on the state of the alpha and beta subunits within nitrosyl haemoglobin. Low temperature photodissociation and the ESR spectra.", "content": "Photodissociation of nitrosyl haemoglobin and nitrosyl hybrids, in which either the alpha or beta subunit is in the nitrosyl form has been stidued at liquid helium temperature (4.2 degrees K) by electron spin resonance and optical absorption spectroscopy. In the presence of inositol hexaphosphate, the photodissociated form of nitrosyl haemoglobin showed an anomalous absorption spectrum in the near infrared region. The experiments with nitrosyl hybrids showed that the alphaNO subunit within the T state haemoglobin is predominantly responsible for the anomalous photodissociated form and the ESR spectrum with three distinct hypefines. The ESR spectrum of alphaNO2betadeoxy2 with inositol hexaphosphate appeared to be very similar to that of the 5-coordinated NO-haem complexes but the absorption spectrum of its photodissociated form was similar to none of protoporphyrin Fe(II) derivatives so far reported. This result suggests that the anomalous photodissociated form may be attributable to some structural distortion of porphyrin or a new electronic state of the haem with different spin state from that of deoxyhaemoglobin.", "contents": "The effect of quaternary structure on the state of the alpha and beta subunits within nitrosyl haemoglobin. Low temperature photodissociation and the ESR spectra. Photodissociation of nitrosyl haemoglobin and nitrosyl hybrids, in which either the alpha or beta subunit is in the nitrosyl form has been stidued at liquid helium temperature (4.2 degrees K) by electron spin resonance and optical absorption spectroscopy. In the presence of inositol hexaphosphate, the photodissociated form of nitrosyl haemoglobin showed an anomalous absorption spectrum in the near infrared region. The experiments with nitrosyl hybrids showed that the alphaNO subunit within the T state haemoglobin is predominantly responsible for the anomalous photodissociated form and the ESR spectrum with three distinct hypefines. The ESR spectrum of alphaNO2betadeoxy2 with inositol hexaphosphate appeared to be very similar to that of the 5-coordinated NO-haem complexes but the absorption spectrum of its photodissociated form was similar to none of protoporphyrin Fe(II) derivatives so far reported. This result suggests that the anomalous photodissociated form may be attributable to some structural distortion of porphyrin or a new electronic state of the haem with different spin state from that of deoxyhaemoglobin."}
{"id": "PMID:202328", "title": "The amino acid sequence of cytochrome c from the blowfly Lucilia cuprina.", "content": "The amino acid sequence of cytochrome c isolated from the sheep blowfly Lucilia cuprina has been determined by comparison of the compositions of the tryptic peptides to those predicted from the published sequences of cytochromes c from other insects. Cytochrome c from L. cuprina differs at a single residue when compared to cytochrome c from the screw worm fly Haematobia irritans, a species belonging to the same order as the blowfly. This substitution, proline for alanine, has been located at position 44 in the protein chain.", "contents": "The amino acid sequence of cytochrome c from the blowfly Lucilia cuprina. The amino acid sequence of cytochrome c isolated from the sheep blowfly Lucilia cuprina has been determined by comparison of the compositions of the tryptic peptides to those predicted from the published sequences of cytochromes c from other insects. Cytochrome c from L. cuprina differs at a single residue when compared to cytochrome c from the screw worm fly Haematobia irritans, a species belonging to the same order as the blowfly. This substitution, proline for alanine, has been located at position 44 in the protein chain."}
{"id": "PMID:202329", "title": "ESR correlation times of 2,2,6,6-tetramethyl piperidone-N-oxyl (Tempone) in solutions of hemoglobin A and hemoglobin S.", "content": "Correlation times for the tumbling motion of the spin probe 2,2,6,6,-tetramethyl piperidone-N-oxyl (Tempone) were obtained in the presence of different concentrations of oxyhemoglobin A, oxyhemoglobin S, and deoxyhemoglobin S and compared to the viscosity of non-gelling hemoglobin solutions. Reorientational motion (or tumbling) of Tempone in gelled solutions of deoxyhemoglobin S is as great as that in non-gelled hemoglobins of the same total concentration. It is concluded that the gel does not exclusively partition Tempone into an aqueous phase of lower solute concentration after gel formation. The gel at room temperature is a highly mobile and dynamic structure on the microscopic level.", "contents": "ESR correlation times of 2,2,6,6-tetramethyl piperidone-N-oxyl (Tempone) in solutions of hemoglobin A and hemoglobin S. Correlation times for the tumbling motion of the spin probe 2,2,6,6,-tetramethyl piperidone-N-oxyl (Tempone) were obtained in the presence of different concentrations of oxyhemoglobin A, oxyhemoglobin S, and deoxyhemoglobin S and compared to the viscosity of non-gelling hemoglobin solutions. Reorientational motion (or tumbling) of Tempone in gelled solutions of deoxyhemoglobin S is as great as that in non-gelled hemoglobins of the same total concentration. It is concluded that the gel does not exclusively partition Tempone into an aqueous phase of lower solute concentration after gel formation. The gel at room temperature is a highly mobile and dynamic structure on the microscopic level."}
{"id": "PMID:202330", "title": "Nuclear magnetic resonance studies of hemoproteins. VIII. Proton NMR studies of the binding of various nitrogenous ligands to ferric cytochrome c.", "content": "The structure of the heme environment of horse heart ferric cytochrome c was examined in the presence of various nitrogenous bases at several temperatures with the aid of hyperfine shifted proton NMR spectra at 220 MHz. The resonance positions and line widths of the signals for the peripheral methyl groups of the heme exhibited distinctive features of its low-spin state characteristic of each external ligand. In the imidazole complex of ferric cytochrome c, remarkable line sharpening of the heme-linked proton signals was encountered on raising the temperature. This may be related to the apoprotein perturbation on the binding of external ligand to the heme iron. These spectral peculiarities were discussed in relation to the electronic structure of the heme, the basicity of the external ligand and the van der Waals contact interaction between heme side chains and apoprotein.", "contents": "Nuclear magnetic resonance studies of hemoproteins. VIII. Proton NMR studies of the binding of various nitrogenous ligands to ferric cytochrome c. The structure of the heme environment of horse heart ferric cytochrome c was examined in the presence of various nitrogenous bases at several temperatures with the aid of hyperfine shifted proton NMR spectra at 220 MHz. The resonance positions and line widths of the signals for the peripheral methyl groups of the heme exhibited distinctive features of its low-spin state characteristic of each external ligand. In the imidazole complex of ferric cytochrome c, remarkable line sharpening of the heme-linked proton signals was encountered on raising the temperature. This may be related to the apoprotein perturbation on the binding of external ligand to the heme iron. These spectral peculiarities were discussed in relation to the electronic structure of the heme, the basicity of the external ligand and the van der Waals contact interaction between heme side chains and apoprotein."}
{"id": "PMID:202331", "title": "Cyclic AMP levels and types I and II cyclic AMP-dependent protein kinase activity in synchronized cells and in quiescent cultures stimulated to proliferate.", "content": "Cyclic AMP as well as the specific activity of cyclic AMP-dependent protein kinase decreased from the first two hours after Chinese hamster ovary cells in plateau phase were stimulated to proliferate by tripsinization of confluent cultures and dilution in fresh media. From two to five hours after this stimulation, the cyclic AMP level and the specific activity of cyclic AMP-dependent protein kinase increased two-fold. There was a 40--50% increase in the degree of activation of cyclic AMP-dependent protein kinase during this same time interval. In plateau cultures prior to being stimulated to proliferate, type I cyclic AMP-dependent protein kinase was the predominant soluble form of these enzymes. At five hours after release from plateau, the predominant type of cyclic AMP-dependent protein kinase was type II. However, there was also a significant amount of type I present at this time. Types I and II cyclic AMP-dependent protein kinases were differentially detectable during the cell cycle of Chinese hamster ovary cells synchronized by mechanical selection of metaphase cells following colcemid treatment. During mitosis, type I kinase was predominant with only a small amount of type II activity detectable. The amount of activity of type I then progressively decreased as cells entered G1. During early G1, there was no detectable activity of type II kinase, but its activity increased from mid to late G1 and then decreased during the S phase. These data show a tight temporal relationship between the levels of cyclic AMP, the total cellular pool of type I and II cyclic AMP-dependent protein kinases, and the degree of activation of these kinases as cells traversed G1 toward S phase. These data suggest that the expression of each type of kinase may be important for the regulation of substrate phosphorylation during the cell cycle.", "contents": "Cyclic AMP levels and types I and II cyclic AMP-dependent protein kinase activity in synchronized cells and in quiescent cultures stimulated to proliferate. Cyclic AMP as well as the specific activity of cyclic AMP-dependent protein kinase decreased from the first two hours after Chinese hamster ovary cells in plateau phase were stimulated to proliferate by tripsinization of confluent cultures and dilution in fresh media. From two to five hours after this stimulation, the cyclic AMP level and the specific activity of cyclic AMP-dependent protein kinase increased two-fold. There was a 40--50% increase in the degree of activation of cyclic AMP-dependent protein kinase during this same time interval. In plateau cultures prior to being stimulated to proliferate, type I cyclic AMP-dependent protein kinase was the predominant soluble form of these enzymes. At five hours after release from plateau, the predominant type of cyclic AMP-dependent protein kinase was type II. However, there was also a significant amount of type I present at this time. Types I and II cyclic AMP-dependent protein kinases were differentially detectable during the cell cycle of Chinese hamster ovary cells synchronized by mechanical selection of metaphase cells following colcemid treatment. During mitosis, type I kinase was predominant with only a small amount of type II activity detectable. The amount of activity of type I then progressively decreased as cells entered G1. During early G1, there was no detectable activity of type II kinase, but its activity increased from mid to late G1 and then decreased during the S phase. These data show a tight temporal relationship between the levels of cyclic AMP, the total cellular pool of type I and II cyclic AMP-dependent protein kinases, and the degree of activation of these kinases as cells traversed G1 toward S phase. These data suggest that the expression of each type of kinase may be important for the regulation of substrate phosphorylation during the cell cycle."}
{"id": "PMID:202334", "title": "Effect of hydrolytic enzymes and protein-modifying reagents on gonadotropin receptors in bovine corpus luteum cell membranes.", "content": "Preincubation of membranes with various concentrations of pronase, trypsin, lipase, phospholipase A from Vipera russelli and from Crotalus durissus terrificus, phospholipase C from Bacillus cereus and from Clostridium welchii, acetic anhydride, 2,4-dinitrofluorobenzene and tetranitromethane resulted in a dose-dependent inhibition of 125I-labeled human choriogonadotropin binding. At the submaximal concentrations of enzymes and at both submaximal and maximal concentrations of protein-modifying reagents, the losses were always greater with 125I-labeled human choriogonadotropin than with 125I-labeled human lutropin. The inhibition of binding was a consequence of changes in the membranes rather than changes in the hormone caused by the agents being carried over to the final incubation. Inhibition of binding was non-competitive and irreversible. In untreated membranes, the 125I-labeled human choriogonadotropin binding was homogeneous (Kd = 1.7.10(-10) M; N = 60 fmol/mg protein). Treatment of membranes with various enzymes and protein-modifying reagents except tetranitromethane resulted in heterogeneous binding. The number of available high affinity receptors was greatly reduced in every case. However, the affinity of these sites were either unchanged (trypsin, lipase, phospholipase A from V. russelli, dinitrofluorobenzene and the tetranitromethane) or decreased (pronase and acetic anhydride). The newly appeared second receptor site had a Kd which varied from 3.2.10(-10) to 7.1.10(-9) M depending on the agent used, and the receptor numbers were low in all cases except acetic anhydride. Receptor occupancy conferred the receptors with marked protection against various hydrolytic enzymes, dinitrofluorobenzene and tetranitromethane. These data suggest that inhibition of binding by the above agents was primarily a consequence of changes in the receptor molecules themselves.", "contents": "Effect of hydrolytic enzymes and protein-modifying reagents on gonadotropin receptors in bovine corpus luteum cell membranes. Preincubation of membranes with various concentrations of pronase, trypsin, lipase, phospholipase A from Vipera russelli and from Crotalus durissus terrificus, phospholipase C from Bacillus cereus and from Clostridium welchii, acetic anhydride, 2,4-dinitrofluorobenzene and tetranitromethane resulted in a dose-dependent inhibition of 125I-labeled human choriogonadotropin binding. At the submaximal concentrations of enzymes and at both submaximal and maximal concentrations of protein-modifying reagents, the losses were always greater with 125I-labeled human choriogonadotropin than with 125I-labeled human lutropin. The inhibition of binding was a consequence of changes in the membranes rather than changes in the hormone caused by the agents being carried over to the final incubation. Inhibition of binding was non-competitive and irreversible. In untreated membranes, the 125I-labeled human choriogonadotropin binding was homogeneous (Kd = 1.7.10(-10) M; N = 60 fmol/mg protein). Treatment of membranes with various enzymes and protein-modifying reagents except tetranitromethane resulted in heterogeneous binding. The number of available high affinity receptors was greatly reduced in every case. However, the affinity of these sites were either unchanged (trypsin, lipase, phospholipase A from V. russelli, dinitrofluorobenzene and the tetranitromethane) or decreased (pronase and acetic anhydride). The newly appeared second receptor site had a Kd which varied from 3.2.10(-10) to 7.1.10(-9) M depending on the agent used, and the receptor numbers were low in all cases except acetic anhydride. Receptor occupancy conferred the receptors with marked protection against various hydrolytic enzymes, dinitrofluorobenzene and tetranitromethane. These data suggest that inhibition of binding by the above agents was primarily a consequence of changes in the receptor molecules themselves."}
{"id": "PMID:202335", "title": "Liver collagen hydroxylation in murine schistosomiasis.", "content": "The activity of procollagen prolyl hydroxylase was measured in fibrotic liver obtained from mice with hepatosplenic schistosomiasis, an animal model of the most prevalent form of human liver fibrosis. Measurable activity of prolyl hydroxylase in fibrotic liver supernatants was 47-fold higher than that of normal liver. The effect of prolyl hydroxylase inhibition on collagen synthesis in fibrotic liver slices was studied, using 8,9-dihydroxy-7-methyl benzo[b]quinolizinium bromide (GPA 1734). This compound was shown in other systems to inhibit prolyl and lysyl hydroxylations by iron chelation at concentrations which did not affect total protein synthesis. The formation of nondialyzable labelled hydroxyproline was inhibited by GPA 1734, 40, 70 and 95% at 30, 50 and 100 micrometer, respectively. Incorporation of proline into total liver protein was unaffected at 30 and 50 micrometer, but was inhibited 20% at 100 micrometer GPA 1734. Underhydroxylated collagen synthesized by liver slices with GPA 1734 was extracted with neutral salt solution and was subsequently hydroxylated with partially-purified prolyl hydroxylase to the same extent as control material synthesized in the absence of GPA 1734.", "contents": "Liver collagen hydroxylation in murine schistosomiasis. The activity of procollagen prolyl hydroxylase was measured in fibrotic liver obtained from mice with hepatosplenic schistosomiasis, an animal model of the most prevalent form of human liver fibrosis. Measurable activity of prolyl hydroxylase in fibrotic liver supernatants was 47-fold higher than that of normal liver. The effect of prolyl hydroxylase inhibition on collagen synthesis in fibrotic liver slices was studied, using 8,9-dihydroxy-7-methyl benzo[b]quinolizinium bromide (GPA 1734). This compound was shown in other systems to inhibit prolyl and lysyl hydroxylations by iron chelation at concentrations which did not affect total protein synthesis. The formation of nondialyzable labelled hydroxyproline was inhibited by GPA 1734, 40, 70 and 95% at 30, 50 and 100 micrometer, respectively. Incorporation of proline into total liver protein was unaffected at 30 and 50 micrometer, but was inhibited 20% at 100 micrometer GPA 1734. Underhydroxylated collagen synthesized by liver slices with GPA 1734 was extracted with neutral salt solution and was subsequently hydroxylated with partially-purified prolyl hydroxylase to the same extent as control material synthesized in the absence of GPA 1734."}
{"id": "PMID:202339", "title": "A fluorescence study of the binding of cytochrome C to mixed-phospholipid microvesicles : evidence for a preferred orientation of the bound protein.", "content": "Kinetic and equilibrium experiments are reported on the binding of the fluorescent probe 1,8-anilino-naphtalene sulfonate (ANS) to microvesicles of natural lecithin containing 10 per cent of an anionic phospholipip (90 : 10 mixtures). Kinetics discriminated between fast binding to the outer leaflet of the bilayer and apparently slow binding to the inner leaflet controlled by the diffusion of the probe across the bilayer. The equilibrium distribution of ANS between the two leaflets was not dependent on the nature of the anionic species and the spectral properties of bound ANS were identical in all cases investigated. A hyperbolic saturation was observed allowing to propose an affinity scale for the binding of ANS to mixtures of lecithin with phosphatidic acid, phosphatidylinositol, and cardiolipin. The effects on binding of ionic strength and sodium dodecylsulfate were also considered. The binding of horse heart ferricytochrome c to ANS-labelled microvesicles was studied quantitatively making use of the quenching of the probes fluorescence by the heme. Perrin-F\u00f6rster energy transfer could be analysed on the basis of a simple model of the physical arrangement of the system which was elaborated from published data referring to ANS and cytochrome c binding to phospholipids. Experimental and theoretical computed values of the quenching efficiency were compared and led to conclude in favor of a preferred orientation of the heme crevice fully accessible from the external space at the lipid interface.", "contents": "A fluorescence study of the binding of cytochrome C to mixed-phospholipid microvesicles : evidence for a preferred orientation of the bound protein. Kinetic and equilibrium experiments are reported on the binding of the fluorescent probe 1,8-anilino-naphtalene sulfonate (ANS) to microvesicles of natural lecithin containing 10 per cent of an anionic phospholipip (90 : 10 mixtures). Kinetics discriminated between fast binding to the outer leaflet of the bilayer and apparently slow binding to the inner leaflet controlled by the diffusion of the probe across the bilayer. The equilibrium distribution of ANS between the two leaflets was not dependent on the nature of the anionic species and the spectral properties of bound ANS were identical in all cases investigated. A hyperbolic saturation was observed allowing to propose an affinity scale for the binding of ANS to mixtures of lecithin with phosphatidic acid, phosphatidylinositol, and cardiolipin. The effects on binding of ionic strength and sodium dodecylsulfate were also considered. The binding of horse heart ferricytochrome c to ANS-labelled microvesicles was studied quantitatively making use of the quenching of the probes fluorescence by the heme. Perrin-F\u00f6rster energy transfer could be analysed on the basis of a simple model of the physical arrangement of the system which was elaborated from published data referring to ANS and cytochrome c binding to phospholipids. Experimental and theoretical computed values of the quenching efficiency were compared and led to conclude in favor of a preferred orientation of the heme crevice fully accessible from the external space at the lipid interface."}
{"id": "PMID:202343", "title": "[Preparative method of isolating phosphoinositide fractions from brain tissue].", "content": "A simple technique for preparative isolation of chromatographically homogenous fractions of mono-, di- and triphosphoinositides from ox brain tissue is described. Podyphosphoinositides fractions were obtained after chromatography of lipid extract on DEAE cellulose, phosphomonoinositides fraction--after chromatography of polyphosphoinositide-free material on aluminium hydroxide column. Bivalent metal ions were eliminated from lipid extract using chromatography on Dowex-50 H+. Ammonium acetate was removed after precipitation of lipids in water: methanol (1:1) in the presence of 4 M this salt. The average yield of mono-, di- and triphosphates was 40, 22 and 58 mg respectively per 1 kg of brain tissue as callulated for lipid phosphorus.", "contents": "[Preparative method of isolating phosphoinositide fractions from brain tissue]. A simple technique for preparative isolation of chromatographically homogenous fractions of mono-, di- and triphosphoinositides from ox brain tissue is described. Podyphosphoinositides fractions were obtained after chromatography of lipid extract on DEAE cellulose, phosphomonoinositides fraction--after chromatography of polyphosphoinositide-free material on aluminium hydroxide column. Bivalent metal ions were eliminated from lipid extract using chromatography on Dowex-50 H+. Ammonium acetate was removed after precipitation of lipids in water: methanol (1:1) in the presence of 4 M this salt. The average yield of mono-, di- and triphosphates was 40, 22 and 58 mg respectively per 1 kg of brain tissue as callulated for lipid phosphorus."}
{"id": "PMID:202345", "title": "An EEG sleep study of a bipolar (manic-depressive) patient with a nocturnal switch process.", "content": "Fifty-eight all-night polygraphic sleep recordings were obtained on an unmedicated female bioplar (manic-depressive) patient who switched into and out of mania eight times. While depressed she was hypersomniac and exhibited elevated Rapid Eye Movement (REM) sleep time and short REM latency. On four nights, she apparently switched into mania while asleep. The last recorded sleep stage in each case was REM sleep.", "contents": "An EEG sleep study of a bipolar (manic-depressive) patient with a nocturnal switch process. Fifty-eight all-night polygraphic sleep recordings were obtained on an unmedicated female bioplar (manic-depressive) patient who switched into and out of mania eight times. While depressed she was hypersomniac and exhibited elevated Rapid Eye Movement (REM) sleep time and short REM latency. On four nights, she apparently switched into mania while asleep. The last recorded sleep stage in each case was REM sleep."}
{"id": "PMID:202346", "title": "A psychophysiological investigation of the short-term effects of clozapine upon sleep parameters of normal young adults.", "content": "A nine consecutive night, double-blind design was used to assess the effects of a psychotropic agent (clozapine) upon sleep parameters as well as measures of mood and performance in a group of seven normal, young adults. Placebo was administered to a control group of seven subjects. EEGs and EOGs were monitored throughout the night in a laboratory environment and were scored according to standardized criteria. The administration of 25 mg clozapine/night for three consecutive nights significantly reduced stage 4 sleep on the second and third nights. Whereas stage REM sleep was not affected, a variety of REM indices were significantly increased on the third night of clozapine administration and/or on the first night of clozapine withdrawal. The number of body movements and the number of body movements/minute of sleep were significantly reduced on the three nights of clozapine administration. Numerous psychophysiological side effects were reported. These results indicate that clozapine may be a useful medication in the treatment of sleep disorders. However, the incidence of adverse side effects of represents a major limitation in the use of clozapine as an hypnotic agent at the dose-rate employed.", "contents": "A psychophysiological investigation of the short-term effects of clozapine upon sleep parameters of normal young adults. A nine consecutive night, double-blind design was used to assess the effects of a psychotropic agent (clozapine) upon sleep parameters as well as measures of mood and performance in a group of seven normal, young adults. Placebo was administered to a control group of seven subjects. EEGs and EOGs were monitored throughout the night in a laboratory environment and were scored according to standardized criteria. The administration of 25 mg clozapine/night for three consecutive nights significantly reduced stage 4 sleep on the second and third nights. Whereas stage REM sleep was not affected, a variety of REM indices were significantly increased on the third night of clozapine administration and/or on the first night of clozapine withdrawal. The number of body movements and the number of body movements/minute of sleep were significantly reduced on the three nights of clozapine administration. Numerous psychophysiological side effects were reported. These results indicate that clozapine may be a useful medication in the treatment of sleep disorders. However, the incidence of adverse side effects of represents a major limitation in the use of clozapine as an hypnotic agent at the dose-rate employed."}
{"id": "PMID:202347", "title": "The role of geometry and elastic strains in dynamic states of proteins.", "content": "A theory is developed, where a linear macromolecule with geometrically constrained ends, elastically strained, exchanging energy with the solvent molecules through random collisions may provide a mechanism for the following specific functions in proteins: a) Induction of transient, oriented strains in substrates during transition between conformations. b) External variation of the rigidity and geometry of the active site. More generally, a macromolecule in solution possessing appropriate geometrical and elastic properties constitutes a machine, whose possible operations have common features with biological function such as passive transport, enzymatic catalysis and active transport. The theory suggests a quantitative law by which new information about the dynamical state of the protein molecule can be elucidated from the Arrhenius plot. It predicts a relationship between the rate of catalysis and the local viscosity of the solution.", "contents": "The role of geometry and elastic strains in dynamic states of proteins. A theory is developed, where a linear macromolecule with geometrically constrained ends, elastically strained, exchanging energy with the solvent molecules through random collisions may provide a mechanism for the following specific functions in proteins: a) Induction of transient, oriented strains in substrates during transition between conformations. b) External variation of the rigidity and geometry of the active site. More generally, a macromolecule in solution possessing appropriate geometrical and elastic properties constitutes a machine, whose possible operations have common features with biological function such as passive transport, enzymatic catalysis and active transport. The theory suggests a quantitative law by which new information about the dynamical state of the protein molecule can be elucidated from the Arrhenius plot. It predicts a relationship between the rate of catalysis and the local viscosity of the solution."}
{"id": "PMID:202348", "title": "[Effect of high temperature on the direct cortical response].", "content": "Acute experiments were conducted on anesthetized cats placed in a thermochamber at a temperature of 45 degrees C. The direct cortical response in suprasylvian convolution of the cortex during hyperthermia and after the restoration of the thermal homeostasis was studied. It was revealed that hyperthermia caused primary inhibition at a temperature of 40 degrees C and above it, and even complete disappearance of the slow negative potential; above 43 degrees C there was found a gradual depression of the dendrite potential. Restoration of body normothermia following high hyperthermia was accompanied by an insignificant tendency to normalization of the slow negative potential parameters. Analysis of the dendrite potential changes on coupled stimuli testified to the fact that high temperature had a preponderant influence on the presynaptic elements of the cortical axodendrite synapses. On the basis of differential action of heat on the component composition of the direct cortical response a conclusion was drawn on the differences in the sensitivity of functionally different cells of the cortex during hyperthermia.", "contents": "[Effect of high temperature on the direct cortical response]. Acute experiments were conducted on anesthetized cats placed in a thermochamber at a temperature of 45 degrees C. The direct cortical response in suprasylvian convolution of the cortex during hyperthermia and after the restoration of the thermal homeostasis was studied. It was revealed that hyperthermia caused primary inhibition at a temperature of 40 degrees C and above it, and even complete disappearance of the slow negative potential; above 43 degrees C there was found a gradual depression of the dendrite potential. Restoration of body normothermia following high hyperthermia was accompanied by an insignificant tendency to normalization of the slow negative potential parameters. Analysis of the dendrite potential changes on coupled stimuli testified to the fact that high temperature had a preponderant influence on the presynaptic elements of the cortical axodendrite synapses. On the basis of differential action of heat on the component composition of the direct cortical response a conclusion was drawn on the differences in the sensitivity of functionally different cells of the cortex during hyperthermia."}
{"id": "PMID:202349", "title": "[Effect of hyperchylomicronemia and hyperprebetalipoproteinemia on the vascular walls of rats of different ages].", "content": "The effect of hyperchylomicronemia and hyperprebetalipo-proteinemia on the vascular wall of 6--10 and 26--30-month-old rats was studied. These animals were injected intravenously with the blood serum taken from rats, preliminarily treated with Triton WR 1339 (intraperitoneal administration). The electron microscopy study revealed the presence of inclusion of chylomicrons and lipoproteins of very low density in the endothelium of old animals only. Swelling of the Golgi complex and mitochondria, expansion of the cysterns of endoplasmic reticulum in the endothelial cells of young rats pointed to the activation of intracellular metabolic processes. The study under these conditions of the biosynthesis of some lipid classes in the aorta showed a similar inhibition of free cholesterol biosynthesis in rats of various age. An increase of phospholipid biosynthesis was recorded in young animals only.", "contents": "[Effect of hyperchylomicronemia and hyperprebetalipoproteinemia on the vascular walls of rats of different ages]. The effect of hyperchylomicronemia and hyperprebetalipo-proteinemia on the vascular wall of 6--10 and 26--30-month-old rats was studied. These animals were injected intravenously with the blood serum taken from rats, preliminarily treated with Triton WR 1339 (intraperitoneal administration). The electron microscopy study revealed the presence of inclusion of chylomicrons and lipoproteins of very low density in the endothelium of old animals only. Swelling of the Golgi complex and mitochondria, expansion of the cysterns of endoplasmic reticulum in the endothelial cells of young rats pointed to the activation of intracellular metabolic processes. The study under these conditions of the biosynthesis of some lipid classes in the aorta showed a similar inhibition of free cholesterol biosynthesis in rats of various age. An increase of phospholipid biosynthesis was recorded in young animals only."}
{"id": "PMID:202350", "title": "[Electrophoretic study of the nuclear membrane ribonucleases of rat liver and hepatoma-27 cells].", "content": "Purified cell nuclei from the rat liver and hepatoma-27 cells were used to prepare nuclear membranes from which the enzyme-containing extracts of acid-soluble proteins were prepared. The protein extracts were subjected to disc-electrophoresis in 15% polyacrylamide gel using modified Reisfeld's system. It was found that ribonucleases contained in the acid-soluble proteins of the nuclear membranes of normal liver are represented as several components, and differed by their electrophoretic mobility and also by some other physical and chemical properties from crystalline bovine ribonuclease, as well as from nuclear chromatine ribonucleases.", "contents": "[Electrophoretic study of the nuclear membrane ribonucleases of rat liver and hepatoma-27 cells]. Purified cell nuclei from the rat liver and hepatoma-27 cells were used to prepare nuclear membranes from which the enzyme-containing extracts of acid-soluble proteins were prepared. The protein extracts were subjected to disc-electrophoresis in 15% polyacrylamide gel using modified Reisfeld's system. It was found that ribonucleases contained in the acid-soluble proteins of the nuclear membranes of normal liver are represented as several components, and differed by their electrophoretic mobility and also by some other physical and chemical properties from crystalline bovine ribonuclease, as well as from nuclear chromatine ribonucleases."}
{"id": "PMID:202351", "title": "[Effect of cholesterol on membrane Na,K-activated adenosine triphosphatase].", "content": "The membrane preparations of rat brain Na,K-ATP-ase with different amount of cholesterol were obtained by using high-cholesterol diet or cholesterol-oxidase treatment. The cholesterol/protein ratio varied from 0.034 to 0.252 (normal--0.152). An increase of this ratio removes the curvature on the Arrhanius' plots for Na,K-ATP-ase, and a decrease--enhances it. The change of the temperature dependence pattern on the enzyme activity correlates with that of the spectral parameter of spin-labelled and rostane analogue, characterizing fluidity of membrane lipids in the same preparations. The authors conclude that the cholesterol level in the brain membranes monitors the activity of the membrane Na,K-ATP-ase.", "contents": "[Effect of cholesterol on membrane Na,K-activated adenosine triphosphatase]. The membrane preparations of rat brain Na,K-ATP-ase with different amount of cholesterol were obtained by using high-cholesterol diet or cholesterol-oxidase treatment. The cholesterol/protein ratio varied from 0.034 to 0.252 (normal--0.152). An increase of this ratio removes the curvature on the Arrhanius' plots for Na,K-ATP-ase, and a decrease--enhances it. The change of the temperature dependence pattern on the enzyme activity correlates with that of the spectral parameter of spin-labelled and rostane analogue, characterizing fluidity of membrane lipids in the same preparations. The authors conclude that the cholesterol level in the brain membranes monitors the activity of the membrane Na,K-ATP-ase."}
{"id": "PMID:202352", "title": "[Mechanisms of the different effect of sucrose on the quantity of lipids in the blood and liver of experimental animals].", "content": "Experiments on rats showed that inclusion of sucrose into the composition of diets with increased or normal carbohydrate content accelerated the synthesis in the liver of apoproteins of pre-beta-lipoproteins and their loading with endogenously formed lipids, promoted a more intensive secretion of lipoproteins of very low density into the blood and an increase in it of the triglyceride level. However, the rate of the lipid compensation with the protein of pre-beta-lipoproteins in the liver depends also on the qualitative ratio of the carbohydrate and fat components in the diet. In using the diet with sucrose with the physiological ratio of carbohydrates and fats (2:1) there was noted a lower load of apoproteins of pre-beta-lipoproteins with lipids, this leading to an increase of the latter in the liver.", "contents": "[Mechanisms of the different effect of sucrose on the quantity of lipids in the blood and liver of experimental animals]. Experiments on rats showed that inclusion of sucrose into the composition of diets with increased or normal carbohydrate content accelerated the synthesis in the liver of apoproteins of pre-beta-lipoproteins and their loading with endogenously formed lipids, promoted a more intensive secretion of lipoproteins of very low density into the blood and an increase in it of the triglyceride level. However, the rate of the lipid compensation with the protein of pre-beta-lipoproteins in the liver depends also on the qualitative ratio of the carbohydrate and fat components in the diet. In using the diet with sucrose with the physiological ratio of carbohydrates and fats (2:1) there was noted a lower load of apoproteins of pre-beta-lipoproteins with lipids, this leading to an increase of the latter in the liver."}
{"id": "PMID:202353", "title": "[Activity of glucose-6-phosphate metabolism enzymes in the livers of rats with experimental valekson poisoning].", "content": "The activity of hexokinase, glucose-6-phosphatase and glucose-6-phosphoric dehydrogenase was studied in the liver of rats after one hour, one and five days after a single oral administration of organic phosphorus insecticide valekson. It was determined that administration of the preparation led to an increase of activity in the homogenate and solubilization of glucose-6-phosphatase, activation of glucose-6-phosphoric dehydrogenase and inhibition of hexokinase. The changes were maximum one hour after the administration of the compound. The results show that a decrease of the intensity of glucose-6-phosphate formation and metabolism is one of the pathogenetic factors in the development of valekson-induced intoxication.", "contents": "[Activity of glucose-6-phosphate metabolism enzymes in the livers of rats with experimental valekson poisoning]. The activity of hexokinase, glucose-6-phosphatase and glucose-6-phosphoric dehydrogenase was studied in the liver of rats after one hour, one and five days after a single oral administration of organic phosphorus insecticide valekson. It was determined that administration of the preparation led to an increase of activity in the homogenate and solubilization of glucose-6-phosphatase, activation of glucose-6-phosphoric dehydrogenase and inhibition of hexokinase. The changes were maximum one hour after the administration of the compound. The results show that a decrease of the intensity of glucose-6-phosphate formation and metabolism is one of the pathogenetic factors in the development of valekson-induced intoxication."}
{"id": "PMID:202354", "title": "[Immunogenicity and thymus-dependence of the polymerized alpha-toxoid of Clostridium perfringens].", "content": "Polymeric alpha-toxoid with a molecular weight of 450 000--600 000 was obtained by condensation of alpha-toxoid of Cl. perfringens, type A, with glutaric aldehyde. Experiments on guinea pigs showed that in the adsorbed preparations the immunogenic properties of both monomeric and polymeric alpha-toxoids are practically identical. The primary immune response after the immunization with nonadsorbed antigens was 3 times greater than that induced by the monomer. Polymerization of alpha-toxoid failed to change its thymus dependency.", "contents": "[Immunogenicity and thymus-dependence of the polymerized alpha-toxoid of Clostridium perfringens]. Polymeric alpha-toxoid with a molecular weight of 450 000--600 000 was obtained by condensation of alpha-toxoid of Cl. perfringens, type A, with glutaric aldehyde. Experiments on guinea pigs showed that in the adsorbed preparations the immunogenic properties of both monomeric and polymeric alpha-toxoids are practically identical. The primary immune response after the immunization with nonadsorbed antigens was 3 times greater than that induced by the monomer. Polymerization of alpha-toxoid failed to change its thymus dependency."}
{"id": "PMID:202356", "title": "The mechanism of action of narcotic analgesics in the guinea-pig ileum.", "content": "1. Intracellular recordings were made from neurones in the myenteric plexus of the guinea-pig ileum. Single myenteric ganglia were maintained in vitro and drugs were applied by adding them to the perfusing solution. 2. Narcotic analgesics hyperpolarized the membrane of a proportion of neurones in the myenteric plexus. 3. The membrane hyperpolarization was sometimes associated with a decrease in input resistance. These effects reduced the excitability of myenteric neurones. 4. The effects of narcotics occurred at low concentrations (10 nM to 1 micrometer), were stereospecific and were reversed by naloxone. 5. It is proposed that the morphine-sensitive neurones may be the cholinergic efferents to the muscle layers. By hyperpolarizing these neurones, morphine may prevent their excitation by electric field stimulation. This may explain why narcotic analgesics reduce the output of acetylcholine and the contractile response of this preparation when it is excited by field stimulation.", "contents": "The mechanism of action of narcotic analgesics in the guinea-pig ileum. 1. Intracellular recordings were made from neurones in the myenteric plexus of the guinea-pig ileum. Single myenteric ganglia were maintained in vitro and drugs were applied by adding them to the perfusing solution. 2. Narcotic analgesics hyperpolarized the membrane of a proportion of neurones in the myenteric plexus. 3. The membrane hyperpolarization was sometimes associated with a decrease in input resistance. These effects reduced the excitability of myenteric neurones. 4. The effects of narcotics occurred at low concentrations (10 nM to 1 micrometer), were stereospecific and were reversed by naloxone. 5. It is proposed that the morphine-sensitive neurones may be the cholinergic efferents to the muscle layers. By hyperpolarizing these neurones, morphine may prevent their excitation by electric field stimulation. This may explain why narcotic analgesics reduce the output of acetylcholine and the contractile response of this preparation when it is excited by field stimulation."}
{"id": "PMID:202357", "title": "Relaxation of smooth muscle following contraction elicited by sympathetic nerve stimulation in vivo.", "content": "1. A method for studying in vivo the process of neuroeffector transmission in the nictitating membrane and nasal blood vessels of the cat is described. 2. Administration of desmethylimipramine or cocaine caused increases in both the amplitude and duration of the nasal and membrane responses which may be explained by inhibition of neuronal uptake of noradrenaline. 3. Phenoxybenzamine depressed the responses to nerve stimulation, but had little effect on the relationship between response amplitude and rate of recovery. 4. The relationship between response amplitude and rate of recovery is discussed and related to the sigmoid shape of a log concentration-response curve.", "contents": "Relaxation of smooth muscle following contraction elicited by sympathetic nerve stimulation in vivo. 1. A method for studying in vivo the process of neuroeffector transmission in the nictitating membrane and nasal blood vessels of the cat is described. 2. Administration of desmethylimipramine or cocaine caused increases in both the amplitude and duration of the nasal and membrane responses which may be explained by inhibition of neuronal uptake of noradrenaline. 3. Phenoxybenzamine depressed the responses to nerve stimulation, but had little effect on the relationship between response amplitude and rate of recovery. 4. The relationship between response amplitude and rate of recovery is discussed and related to the sigmoid shape of a log concentration-response curve."}
{"id": "PMID:202358", "title": "Kinin, kininogen and kininase levels during acute Babesia bovis (= B. argentina) infection of cattle.", "content": "1. Kinin levels began rising on day 3 after infection of cattle with Babesia bovis (= B. argentina) and attained a maximum value of 98% above preinfection levels by day 7. 2. Kininogen levels began falling on day 3 and reached minimum levels of 83% below preinfection levels on day 8. 3. Changes in both kinin and kininogen levels on day 3 coincided with the detection of low levels of parasites, and with a fall in packed cell volume. 4. Plasma kininase levels rose significantly 6 to 9 days after infection. Preparations of lysed and sonicated uninfected and infected red cells contained kininase activity, the respective red cell preparations being 23.9 and 11.4 times more active per mg protein than uninfected red cell preparations. The effect of pH, and the inhibitors disodium edetate, 1,10 phenanthroline and aprotinin on normal and infected plasma and on the various red cell preparations suggested that the rise in plasma kininase levels during infection was probably at least partly due to parasite products. 5. These results are discussed in relation to previous data showing that both kallikrein activation and the onset of hypotension also occur on or about day 3.", "contents": "Kinin, kininogen and kininase levels during acute Babesia bovis (= B. argentina) infection of cattle. 1. Kinin levels began rising on day 3 after infection of cattle with Babesia bovis (= B. argentina) and attained a maximum value of 98% above preinfection levels by day 7. 2. Kininogen levels began falling on day 3 and reached minimum levels of 83% below preinfection levels on day 8. 3. Changes in both kinin and kininogen levels on day 3 coincided with the detection of low levels of parasites, and with a fall in packed cell volume. 4. Plasma kininase levels rose significantly 6 to 9 days after infection. Preparations of lysed and sonicated uninfected and infected red cells contained kininase activity, the respective red cell preparations being 23.9 and 11.4 times more active per mg protein than uninfected red cell preparations. The effect of pH, and the inhibitors disodium edetate, 1,10 phenanthroline and aprotinin on normal and infected plasma and on the various red cell preparations suggested that the rise in plasma kininase levels during infection was probably at least partly due to parasite products. 5. These results are discussed in relation to previous data showing that both kallikrein activation and the onset of hypotension also occur on or about day 3."}
{"id": "PMID:202359", "title": "The mode of action at the mouse neuromuscular junction of the phospholipase A-crotapotin complex isolated from venom of the South American rattlesnake.", "content": "1 Phospholipase A(2)-crotapotin complex (P-C complex) isolated from the venom of Crotalus durissus terrificus induced an irreversible blockade of neuromuscular transmission when twitch tension was measured in the mouse phrenic nerve-hemidiaphragm preparation in vitro at 37 degrees C.2 A similar concentration of the phospholipase A(2) (10 mug/ml) alone did not affect neuromuscular transmission and no priming action was detected on later addition of crotapotin.3 The rate of neuromuscular blockade induced by P-C complex (15 mug/ml) was not altered by raising the frequency of nerve stimulation. Lower temperatures markedly increased the time of onset and reduced the rate of blockade (Q(10) (27-37 degrees C) of 4.4) whilst replacement of Ca by Sr in the medium prevented this activity. These latter results suggest that enzymatic activity is important in the neurotoxicity of the complex.4 A myotoxic action was shown by 30 mug/ml P-C complex and 30 mug/ml phospholipase A(2).5 P-C complex (150 mug) was injected into the tail vein of mice and the intoxicated hemidiaphragm preparation removed for intracellular recording at 25 degrees C.6 In fully intoxicated hemidiaphragms, resting membrane potentials were unaltered and endplate potentials (e.p.ps) varied in average amplitude from zero to less than 3 mV.7 Miniature endplate potential (m.e.p.p.) frequency was lower at fully poisoned endplates than at controls; the frequency rose during a 50 Hz tetanus but was unaffected by either raising external K or the application of the Ca-ionophore A23187.8 E.p.ps were recorded in partially intoxicated hemidiaphragms with (+)-tubocurarine (0.5-1.0 mug/ml) added to prevent contraction. Evoked release was abnormal as 50 Hz tetanus elicited e.p.ps of very variable amplitude, no facilitation of response was shown to paired stimuli, and tetraethylammonium (0.5 mM) failed to increase e.p.p. amplitudes.9 M.e.p.ps and e.p.ps were recorded at partially poisoned endplates in low Ca-high Mg solution. A reduction in the quantal content of evoked transmitter release was observed in comparison with controls.10 M.e.p.ps recorded at partially and at fully intoxicated endplates showed an altered amplitude distribution with a higher proportion of large potentials.11 It is concluded that P-C complex has a presynaptic site of action and may interfere with depolarization-secretion coupling at the motor nerve terminals.", "contents": "The mode of action at the mouse neuromuscular junction of the phospholipase A-crotapotin complex isolated from venom of the South American rattlesnake. 1 Phospholipase A(2)-crotapotin complex (P-C complex) isolated from the venom of Crotalus durissus terrificus induced an irreversible blockade of neuromuscular transmission when twitch tension was measured in the mouse phrenic nerve-hemidiaphragm preparation in vitro at 37 degrees C.2 A similar concentration of the phospholipase A(2) (10 mug/ml) alone did not affect neuromuscular transmission and no priming action was detected on later addition of crotapotin.3 The rate of neuromuscular blockade induced by P-C complex (15 mug/ml) was not altered by raising the frequency of nerve stimulation. Lower temperatures markedly increased the time of onset and reduced the rate of blockade (Q(10) (27-37 degrees C) of 4.4) whilst replacement of Ca by Sr in the medium prevented this activity. These latter results suggest that enzymatic activity is important in the neurotoxicity of the complex.4 A myotoxic action was shown by 30 mug/ml P-C complex and 30 mug/ml phospholipase A(2).5 P-C complex (150 mug) was injected into the tail vein of mice and the intoxicated hemidiaphragm preparation removed for intracellular recording at 25 degrees C.6 In fully intoxicated hemidiaphragms, resting membrane potentials were unaltered and endplate potentials (e.p.ps) varied in average amplitude from zero to less than 3 mV.7 Miniature endplate potential (m.e.p.p.) frequency was lower at fully poisoned endplates than at controls; the frequency rose during a 50 Hz tetanus but was unaffected by either raising external K or the application of the Ca-ionophore A23187.8 E.p.ps were recorded in partially intoxicated hemidiaphragms with (+)-tubocurarine (0.5-1.0 mug/ml) added to prevent contraction. Evoked release was abnormal as 50 Hz tetanus elicited e.p.ps of very variable amplitude, no facilitation of response was shown to paired stimuli, and tetraethylammonium (0.5 mM) failed to increase e.p.p. amplitudes.9 M.e.p.ps and e.p.ps were recorded at partially poisoned endplates in low Ca-high Mg solution. A reduction in the quantal content of evoked transmitter release was observed in comparison with controls.10 M.e.p.ps recorded at partially and at fully intoxicated endplates showed an altered amplitude distribution with a higher proportion of large potentials.11 It is concluded that P-C complex has a presynaptic site of action and may interfere with depolarization-secretion coupling at the motor nerve terminals."}
{"id": "PMID:202360", "title": "The action of melatonin on single amphibian pigment cells in tissue culture.", "content": "1. Neural crest material from neurula stage Xenopus embryos was tissue cultured as small aggregates of cells or a single cell suspension. Isolated pigment cells differentiated after 2 days in culture. 2. Melatonin (10(-15) to 10(-13) M) induced pigment granule condensation; it was 10,000 times more effective than any other compound tested. 3. Tests with appropriate agents showed the pigment cells to have beta-adrenoceptors and 5-hydroxytryptamine receptors; these sites could be blocked without affecting the response to melatonin. Phentolamine blocked the effect of melatonin. 4. Removal of Na+ or Ca2+ from the bathing medium inhibited melatonin-induced pigment granule condensation; 10 mM K+ induced pigment granule condensation. D600, Mn2+ and La3+, which inhibit Ca2+ entry, blocked the effect of melatonin. 5. Cyclic GMP induced pigment condensation and cyclic AMP pigment dispersion (10(-2) to 10(-4) M). 6. It is suggested that the action of melatonin is accompanied by depolarization and the entry of calcium ions. 7. Pigment cells in tissue culture could provide a useful bioassay method for melatonin.", "contents": "The action of melatonin on single amphibian pigment cells in tissue culture. 1. Neural crest material from neurula stage Xenopus embryos was tissue cultured as small aggregates of cells or a single cell suspension. Isolated pigment cells differentiated after 2 days in culture. 2. Melatonin (10(-15) to 10(-13) M) induced pigment granule condensation; it was 10,000 times more effective than any other compound tested. 3. Tests with appropriate agents showed the pigment cells to have beta-adrenoceptors and 5-hydroxytryptamine receptors; these sites could be blocked without affecting the response to melatonin. Phentolamine blocked the effect of melatonin. 4. Removal of Na+ or Ca2+ from the bathing medium inhibited melatonin-induced pigment granule condensation; 10 mM K+ induced pigment granule condensation. D600, Mn2+ and La3+, which inhibit Ca2+ entry, blocked the effect of melatonin. 5. Cyclic GMP induced pigment condensation and cyclic AMP pigment dispersion (10(-2) to 10(-4) M). 6. It is suggested that the action of melatonin is accompanied by depolarization and the entry of calcium ions. 7. Pigment cells in tissue culture could provide a useful bioassay method for melatonin."}
{"id": "PMID:202361", "title": "An inhibitory role for noradrenaline in the mouse vas deferens.", "content": "1 Noradrenaline (0.1-3.0 muM) inhibited the twitch responses to single pulse field stimulation of the isolated vas deferens of the mouse. The higher concentrations of noradrenaline (ca. 0.3-3.0 muM) were required to make the tissue contract.2 Phentolamine (10 muM) abolished the contractor response to higher concentrations of noradrenaline and antagonized the inhibitory effect of lower concentrations on the twitch response.3 Propranolol (10 muM) potentiated both the contractor and the inhibitory effect of noradrenaline on the twitch response.4 Isoprenaline (0.1-3.0 muM) and salbutamol (1.0-3.0 muM) both inhibited the twitch response. Their effects were antagonized by propranolol (10 muM), but not by practolol (10 muM).5 The effects of uptake(1) and uptake(2) blocking agents were determined. Cocaine (10 muM) reduced the size of the twitch response in 2 out of 4 experiments. Imipramine (0.18 muM) also reduced the size of the twitch, as did oestradiol (3.7 muM) and a combination of cocaine and oestradiol.6 Contractor responses to exogenous noradrenaline showed tachyphylaxis, but when this was not very marked, the response could be shown to be potentiated by uptake blocking agents.7 The inhibitory effect of noradrenaline on the twitch response was greatly potentiated by cocaine (10 muM) and much less so by oestradiol (3.7 muM).8 It is concluded that the transmitter responsible for the twitch response is either an unknown substance released from the sympathetic neurone, or noradrenaline acting upon a receptor with none of the characteristics of known alpha- or beta-adrenoceptors. In either case, noradrenaline can inhibit the output, probably by stimulation of presynaptic alpha-adrenoceptors.", "contents": "An inhibitory role for noradrenaline in the mouse vas deferens. 1 Noradrenaline (0.1-3.0 muM) inhibited the twitch responses to single pulse field stimulation of the isolated vas deferens of the mouse. The higher concentrations of noradrenaline (ca. 0.3-3.0 muM) were required to make the tissue contract.2 Phentolamine (10 muM) abolished the contractor response to higher concentrations of noradrenaline and antagonized the inhibitory effect of lower concentrations on the twitch response.3 Propranolol (10 muM) potentiated both the contractor and the inhibitory effect of noradrenaline on the twitch response.4 Isoprenaline (0.1-3.0 muM) and salbutamol (1.0-3.0 muM) both inhibited the twitch response. Their effects were antagonized by propranolol (10 muM), but not by practolol (10 muM).5 The effects of uptake(1) and uptake(2) blocking agents were determined. Cocaine (10 muM) reduced the size of the twitch response in 2 out of 4 experiments. Imipramine (0.18 muM) also reduced the size of the twitch, as did oestradiol (3.7 muM) and a combination of cocaine and oestradiol.6 Contractor responses to exogenous noradrenaline showed tachyphylaxis, but when this was not very marked, the response could be shown to be potentiated by uptake blocking agents.7 The inhibitory effect of noradrenaline on the twitch response was greatly potentiated by cocaine (10 muM) and much less so by oestradiol (3.7 muM).8 It is concluded that the transmitter responsible for the twitch response is either an unknown substance released from the sympathetic neurone, or noradrenaline acting upon a receptor with none of the characteristics of known alpha- or beta-adrenoceptors. In either case, noradrenaline can inhibit the output, probably by stimulation of presynaptic alpha-adrenoceptors."}
{"id": "PMID:202362", "title": "Diuretics and the renal adenylate cyclase system.", "content": "1 The relationship between the diuretic effectiveness and the effect on the renal adenylate cyclase of three diuretics, acetazolamide, frusemide and ethacrynic acid, was examined. The hypothesis that acetazolamide and parathyroid hormone (PTH), inhibit renal carbonic anhydrase by a cyclic adenosine 3',5'-monophosphate (cyclic AMP)-dependent mechanism was also tested.2In vitro, acetazolamide, frusemide and ethacrynic acid at high concentrations (10(-3)M) all produced some inhibition of basal and stimulated rat kidney plasma membrane adenylate cyclase. The effect of acetazolamide was much less than that of frusemide and ethacrynic acid. These plasma membrane effects were reproduced in studies of cyclic AMP formation in isolated kidney tubules of rats.3 Intravenous injections of acetazolamide did not change the total cyclic AMP content of the kidneys of rats killed by microwave irradiation.4 Acetazolamide produced a diuresis in the rat and a slight inhibition of the antidiuretic effect of Pitressin. Frusemide produced a diuresis and greatly reduced the antidiuretic response to Pitressin. Ethacrynic acid was ineffective as a diuretic in the rat and actually enhanced the antidiuretic response to Pitressin.5 In investigating the possible influence of diuretics and PTH on the activity and state of phosphorylation of carbonic anhydrase it was found that: there was no correlation between the ability of diuretics to inhibit carbonic anhydrase activity and to inhibit carbonic anhydrase phosphorylation; neither PTH nor cyclic AMP (in the presence of adenosine triphosphate, Mg(2+), K(+) and incubation at 37 degrees C) inhibited rat cortex homogenate carbonic anhydrase activity.6 It seems unlikely that any of the tested diuretics exerts its pharmacological effect by means of changes in kidney cyclic AMP metabolism.", "contents": "Diuretics and the renal adenylate cyclase system. 1 The relationship between the diuretic effectiveness and the effect on the renal adenylate cyclase of three diuretics, acetazolamide, frusemide and ethacrynic acid, was examined. The hypothesis that acetazolamide and parathyroid hormone (PTH), inhibit renal carbonic anhydrase by a cyclic adenosine 3',5'-monophosphate (cyclic AMP)-dependent mechanism was also tested.2In vitro, acetazolamide, frusemide and ethacrynic acid at high concentrations (10(-3)M) all produced some inhibition of basal and stimulated rat kidney plasma membrane adenylate cyclase. The effect of acetazolamide was much less than that of frusemide and ethacrynic acid. These plasma membrane effects were reproduced in studies of cyclic AMP formation in isolated kidney tubules of rats.3 Intravenous injections of acetazolamide did not change the total cyclic AMP content of the kidneys of rats killed by microwave irradiation.4 Acetazolamide produced a diuresis in the rat and a slight inhibition of the antidiuretic effect of Pitressin. Frusemide produced a diuresis and greatly reduced the antidiuretic response to Pitressin. Ethacrynic acid was ineffective as a diuretic in the rat and actually enhanced the antidiuretic response to Pitressin.5 In investigating the possible influence of diuretics and PTH on the activity and state of phosphorylation of carbonic anhydrase it was found that: there was no correlation between the ability of diuretics to inhibit carbonic anhydrase activity and to inhibit carbonic anhydrase phosphorylation; neither PTH nor cyclic AMP (in the presence of adenosine triphosphate, Mg(2+), K(+) and incubation at 37 degrees C) inhibited rat cortex homogenate carbonic anhydrase activity.6 It seems unlikely that any of the tested diuretics exerts its pharmacological effect by means of changes in kidney cyclic AMP metabolism."}
{"id": "PMID:202363", "title": "An estimate of the equilibrium dissociation constant for calcium as an antagonist of evoked acetylcholine release: implications for excitation-secretion coupling.", "content": "The equilibrium dissociation constant (K(d)) for Ca(2+) as an antagonist of evoked acetylcholine (ACh) release was determined in the hope of distinguishing whether divalent cations control excitation-secretion coupling selectively (by binding with high affinity to an external membrane site) or non-selectively (by screening fixed negative charges on the external surface of the nerve terminal). ACh release was detected electrophysiologically by means of conventional intracellular recording techniques at frog motor endplates. Ba(2+) was used as the agonist to support the asynchronous release of ACh by repetitive motor nerve impulses. Despite its dispersed nature, release mediated by Ba(2+) occurs through the same conductance pathway as synchronous release mediated by Ca(2+). Ca(2+) was found to be a potent antagonist of Ba(2+)-dependent release with a K(d)=0.12+/-0.02 mM (mean+/-s.e. mean, n=5). This value is 30-50 times lower than the K(d) for Mg(2+) as an antagonist of the same release process. It is suggested that antagonism of release by Ca(2+) is likely to be exerted at the same external site that binds other divalent cation antagonists, a site that appears essential for the agonist behaviour of Ca(2+). The high affinity (low K(d)) of Ca(2+) as an antagonist of ACh release suggests that a selective, binding model appears to be the most appropriate single description of the action of divalent cations at the external surface of the motor nerve ending.", "contents": "An estimate of the equilibrium dissociation constant for calcium as an antagonist of evoked acetylcholine release: implications for excitation-secretion coupling. The equilibrium dissociation constant (K(d)) for Ca(2+) as an antagonist of evoked acetylcholine (ACh) release was determined in the hope of distinguishing whether divalent cations control excitation-secretion coupling selectively (by binding with high affinity to an external membrane site) or non-selectively (by screening fixed negative charges on the external surface of the nerve terminal). ACh release was detected electrophysiologically by means of conventional intracellular recording techniques at frog motor endplates. Ba(2+) was used as the agonist to support the asynchronous release of ACh by repetitive motor nerve impulses. Despite its dispersed nature, release mediated by Ba(2+) occurs through the same conductance pathway as synchronous release mediated by Ca(2+). Ca(2+) was found to be a potent antagonist of Ba(2+)-dependent release with a K(d)=0.12+/-0.02 mM (mean+/-s.e. mean, n=5). This value is 30-50 times lower than the K(d) for Mg(2+) as an antagonist of the same release process. It is suggested that antagonism of release by Ca(2+) is likely to be exerted at the same external site that binds other divalent cation antagonists, a site that appears essential for the agonist behaviour of Ca(2+). The high affinity (low K(d)) of Ca(2+) as an antagonist of ACh release suggests that a selective, binding model appears to be the most appropriate single description of the action of divalent cations at the external surface of the motor nerve ending."}
{"id": "PMID:202364", "title": "beta-Adrenoceptor stimulation of exocrine secretion from the rat pancreas.", "content": "1 Effects of catecholamines given intravenously on exocrine secretion from the pancreas were investigated in anaesthetized rats. The flow rate of pancreatic juice under resting conditions was 11.1 +/- 3.2 microliter per hour in 100 animals. 2 Dopamine (0.3--3 mg/kg) and isoprenaline (1--10 microgram/kg) induced almost the same increase in the pancreatic secretion, so that dopamine was 300 times less potent than isoprenaline. The relative potency of the two amines for stimulation of pancreatic secretion was equivalent to that for beta-stimulation of the contractile force of the left ventricle in vivo. 3 Propranolol (0.5 mg/kg) antagonized completely the dopamine- and isoprenaline-induced stimulation of the pancreatic secretion. 4 Haloperidol (10 mg/kg) failed to suppress the secretory effect of dopamine on the exocrine pancreas but abolished the dopamine-induced hypotension. 5 The dopamine-induced secretion was not modified by atropine (3 mg/kg), phenoxybenzamine (3 mg/kg), vagotomy or pithing. 6 Adrenaline and noradrenaline (10 microgram/kg) induced secretion after phenoxybenzamine  treatment (3 mg/kg). 7 It is suggested that the rat pancreas has a stimulatory beta-adrenoceptor mechanism of exocrine secretion.", "contents": "beta-Adrenoceptor stimulation of exocrine secretion from the rat pancreas. 1 Effects of catecholamines given intravenously on exocrine secretion from the pancreas were investigated in anaesthetized rats. The flow rate of pancreatic juice under resting conditions was 11.1 +/- 3.2 microliter per hour in 100 animals. 2 Dopamine (0.3--3 mg/kg) and isoprenaline (1--10 microgram/kg) induced almost the same increase in the pancreatic secretion, so that dopamine was 300 times less potent than isoprenaline. The relative potency of the two amines for stimulation of pancreatic secretion was equivalent to that for beta-stimulation of the contractile force of the left ventricle in vivo. 3 Propranolol (0.5 mg/kg) antagonized completely the dopamine- and isoprenaline-induced stimulation of the pancreatic secretion. 4 Haloperidol (10 mg/kg) failed to suppress the secretory effect of dopamine on the exocrine pancreas but abolished the dopamine-induced hypotension. 5 The dopamine-induced secretion was not modified by atropine (3 mg/kg), phenoxybenzamine (3 mg/kg), vagotomy or pithing. 6 Adrenaline and noradrenaline (10 microgram/kg) induced secretion after phenoxybenzamine  treatment (3 mg/kg). 7 It is suggested that the rat pancreas has a stimulatory beta-adrenoceptor mechanism of exocrine secretion."}
{"id": "PMID:202365", "title": "The influence of prostaglandins on noradrenaline-induced vasoconstriction isolated perfused mesenteric blood vessels of the rat.", "content": "1 The report of the depression by indomethacin of vasoconstrictor responses to noradrenaline and their partial restoration by prostaglandin E(2) (PGE(2)) and PGE(1) in rat isolated perfused mesenteric blood vessels was investigated. The further suggestion that prostaglandins may be necessary for the combination of noradrenaline with the alpha-adrenoceptor in this tissue was also studied.2 The reported depression by indomethacin was confirmed and was further shown to be in the form of a concentration-dependent flattening of the noradrenaline concentration-effect curve.3 A concentration-dependent restorative effect was observed for all prostaglandins studied. The decreasing order of potency for the restoration towards normal of the indomethacin-depressed responses to noradrenaline was: PGE(2), PGE(1), PGA(1), PGF(2alpha), PGA(2).4 The prostaglandins studied were not uniform in their restorative actions and could be separated into two groups. PGE(2) and PGE(1) restored responses towards the control level whereas PGA(1), PGA(2) and PGF(2alpha) increased responses to an above control level and did so over a smaller concentration range. The possibility of several prostaglandin receptors is discussed.5 At concentrations equi-effective in restoring depressed responses to control levels PGA(1) but not PGE(2), caused a parallel shift of the noradrenaline concentration-effect curve to the left and a small, gradual rise in the basal perfusion pressure.6 The reason for the differing effects remains obscure but does not seem to involve a change in the alpha-adrenoceptor as indicated by the pA(2) of phentolamine. Furthermore, the restorative and potentiating effect of PGA(1) is not mediated by blockade of neuronal uptake of noradrenaline.7 It appears that prostaglandins are required for the vasoconstrictor action of noradrenaline in rat mesenteric blood vessels and that this effect is distal to the drug-receptor interaction. The possible involvement of prostaglandins with intracellular calcium ions is discussed.", "contents": "The influence of prostaglandins on noradrenaline-induced vasoconstriction isolated perfused mesenteric blood vessels of the rat. 1 The report of the depression by indomethacin of vasoconstrictor responses to noradrenaline and their partial restoration by prostaglandin E(2) (PGE(2)) and PGE(1) in rat isolated perfused mesenteric blood vessels was investigated. The further suggestion that prostaglandins may be necessary for the combination of noradrenaline with the alpha-adrenoceptor in this tissue was also studied.2 The reported depression by indomethacin was confirmed and was further shown to be in the form of a concentration-dependent flattening of the noradrenaline concentration-effect curve.3 A concentration-dependent restorative effect was observed for all prostaglandins studied. The decreasing order of potency for the restoration towards normal of the indomethacin-depressed responses to noradrenaline was: PGE(2), PGE(1), PGA(1), PGF(2alpha), PGA(2).4 The prostaglandins studied were not uniform in their restorative actions and could be separated into two groups. PGE(2) and PGE(1) restored responses towards the control level whereas PGA(1), PGA(2) and PGF(2alpha) increased responses to an above control level and did so over a smaller concentration range. The possibility of several prostaglandin receptors is discussed.5 At concentrations equi-effective in restoring depressed responses to control levels PGA(1) but not PGE(2), caused a parallel shift of the noradrenaline concentration-effect curve to the left and a small, gradual rise in the basal perfusion pressure.6 The reason for the differing effects remains obscure but does not seem to involve a change in the alpha-adrenoceptor as indicated by the pA(2) of phentolamine. Furthermore, the restorative and potentiating effect of PGA(1) is not mediated by blockade of neuronal uptake of noradrenaline.7 It appears that prostaglandins are required for the vasoconstrictor action of noradrenaline in rat mesenteric blood vessels and that this effect is distal to the drug-receptor interaction. The possible involvement of prostaglandins with intracellular calcium ions is discussed."}
{"id": "PMID:202366", "title": "Immune status of children of immigrants to poliomyelitis.", "content": "Four ethnic groups of children from the Glasgow area--155 Asians, 85 Africans, 85 Chinese, and 93 Scots--were examined for neutralising to poliovirus types 1, 2, and 3. Only seven of the 418 children had no detectable antibody, and of these, four were aged less than 7 months; none had received polio vaccine. The best-protected children were the Chinese (93% with antibody to all three poliovirus types), followed by the African (81%), Scottish (78%), and Asian children (77%). We conclude that children of immigrants are no more vulnerable to poliovirus infection than their Scottish counterparts.", "contents": "Immune status of children of immigrants to poliomyelitis. Four ethnic groups of children from the Glasgow area--155 Asians, 85 Africans, 85 Chinese, and 93 Scots--were examined for neutralising to poliovirus types 1, 2, and 3. Only seven of the 418 children had no detectable antibody, and of these, four were aged less than 7 months; none had received polio vaccine. The best-protected children were the Chinese (93% with antibody to all three poliovirus types), followed by the African (81%), Scottish (78%), and Asian children (77%). We conclude that children of immigrants are no more vulnerable to poliovirus infection than their Scottish counterparts."}
{"id": "PMID:202375", "title": "Methods for the study of the glycoproteins and proteoglycans of bone using bacterial collagenase. Determination of bone sialoprotein and chondroitin sulphate.", "content": "A method has been developed for the solubilization of bone matrix using bacterial collagenase. The soluble macromolecules were separated by a column procedure on DEAE-cellulose and analysed for uronic and sialic acids. Values for the total non-collagenous fraction of bone and its content of bone sialoprotein and chondroitin sulphate were obtained. The method was compared with similar procedures using EDTA extraction and papain digestion.", "contents": "Methods for the study of the glycoproteins and proteoglycans of bone using bacterial collagenase. Determination of bone sialoprotein and chondroitin sulphate. A method has been developed for the solubilization of bone matrix using bacterial collagenase. The soluble macromolecules were separated by a column procedure on DEAE-cellulose and analysed for uronic and sialic acids. Values for the total non-collagenous fraction of bone and its content of bone sialoprotein and chondroitin sulphate were obtained. The method was compared with similar procedures using EDTA extraction and papain digestion."}
{"id": "PMID:202376", "title": "Absence of mitochondrial terminal respiratory enzymes in cartilage matrix vesicles.", "content": "This study attempted to detect evidence of mitochondrial terminal respiratory components in matrix vesicles isolated from rachitic rat tibial epiphyseal plates. Biochemical assays for cytochrome c oxidase, NAD isocitrate dehydrogenase, NADP isocitrate dehydrogenase and succinate-cytochrome c reductase were negative. Polarimetric determinations revealed that the addition of succinate to matrix vesicles in suspension did not cause any increase in oxygen utilization. Spectrophotometric tracings of deoxycholate-solubilized matrix vesicles showed no characteristic absorption peaks or maxima belonging to any of the cytochrome complex components. Attempts to prepare pyridine hemochromes of cytochrome prosthetic groups from the matrix vesicles were also unsuccessful. The above results indicate that key components of mitochondrial respiratory systems are not detectable in rachitic matrix vesicles. The results are compatible with the interpretation that such vesicles are not derived from mitochondria.", "contents": "Absence of mitochondrial terminal respiratory enzymes in cartilage matrix vesicles. This study attempted to detect evidence of mitochondrial terminal respiratory components in matrix vesicles isolated from rachitic rat tibial epiphyseal plates. Biochemical assays for cytochrome c oxidase, NAD isocitrate dehydrogenase, NADP isocitrate dehydrogenase and succinate-cytochrome c reductase were negative. Polarimetric determinations revealed that the addition of succinate to matrix vesicles in suspension did not cause any increase in oxygen utilization. Spectrophotometric tracings of deoxycholate-solubilized matrix vesicles showed no characteristic absorption peaks or maxima belonging to any of the cytochrome complex components. Attempts to prepare pyridine hemochromes of cytochrome prosthetic groups from the matrix vesicles were also unsuccessful. The above results indicate that key components of mitochondrial respiratory systems are not detectable in rachitic matrix vesicles. The results are compatible with the interpretation that such vesicles are not derived from mitochondria."}
{"id": "PMID:202377", "title": "Chromatographic separation of two acid phosphatases from rat bone.", "content": "Extracts of tibiae of suckling rats were prepared with 0.3 M KCl containing 0.1% Triton X-100 and were chromatographed with CM-52 cellulose. Most of the acid phosphatase activity determined with p-nitrophenylphosphate (p-NPP) was bound to the cellulose and could be eluted with a sodium acetate buffer gradient in 2 distinct peaks. The major peak, E2, was bound strongly to the cellulose and showed high activity with p-NPP and inorganic pyrophosphate (P-Pi), but only slight activity with beta-glycerophosphate (beta-GP) and was unaffected by tartrate. The minor peak, E1, was weakly bound to the adsorbent, showed equal activity with p-NPP and beta-GP, but negligible activity with P-Pi and was completely inhibited by tartrate. These results support earlier evidence suggesting that bone contains at least 2 different acid phosphatases and that the more abundant enzyme may function as a pyrophosphatase.", "contents": "Chromatographic separation of two acid phosphatases from rat bone. Extracts of tibiae of suckling rats were prepared with 0.3 M KCl containing 0.1% Triton X-100 and were chromatographed with CM-52 cellulose. Most of the acid phosphatase activity determined with p-nitrophenylphosphate (p-NPP) was bound to the cellulose and could be eluted with a sodium acetate buffer gradient in 2 distinct peaks. The major peak, E2, was bound strongly to the cellulose and showed high activity with p-NPP and inorganic pyrophosphate (P-Pi), but only slight activity with beta-glycerophosphate (beta-GP) and was unaffected by tartrate. The minor peak, E1, was weakly bound to the adsorbent, showed equal activity with p-NPP and beta-GP, but negligible activity with P-Pi and was completely inhibited by tartrate. These results support earlier evidence suggesting that bone contains at least 2 different acid phosphatases and that the more abundant enzyme may function as a pyrophosphatase."}
{"id": "PMID:202379", "title": "An improved procedure for the purification of plasma membranes from Dictyostelium discoideum.", "content": "A novel procedure was recently described for the purification of plasma membranes of Dictyostelium discoideum (Gilkes, N. R. & Weeks, G. (1977) Biochim. Biophys. Acta 464, 142-156). Considerable enrichment of plasma membrane marker enzymes was achieved, but since purified mitochondrial and endoplasmic reticulum fractions were unavailable, it was not possible to accurately assess the contamination level of these organelles. We have therefore slightly modified the plasma membrane preparation procedure, improving purification, and have prepared partially purified mitochondrial and endoplasmic reticulum fractions. The data suggest that the contamination of the plasma membranes by endoplasmic reticulum membranes is no greater than 10%, and probably considerably less. No mitochondrial contamination is detectable.", "contents": "An improved procedure for the purification of plasma membranes from Dictyostelium discoideum. A novel procedure was recently described for the purification of plasma membranes of Dictyostelium discoideum (Gilkes, N. R. & Weeks, G. (1977) Biochim. Biophys. Acta 464, 142-156). Considerable enrichment of plasma membrane marker enzymes was achieved, but since purified mitochondrial and endoplasmic reticulum fractions were unavailable, it was not possible to accurately assess the contamination level of these organelles. We have therefore slightly modified the plasma membrane preparation procedure, improving purification, and have prepared partially purified mitochondrial and endoplasmic reticulum fractions. The data suggest that the contamination of the plasma membranes by endoplasmic reticulum membranes is no greater than 10%, and probably considerably less. No mitochondrial contamination is detectable."}
{"id": "PMID:202380", "title": "Increased response of adipose tissue of the ob/ob mouse to the action of adrenaline after treatment with thyroxin.", "content": "The activity of the lipolytic system of the obese hyperglycemic mouse was assessed after treatment with physiological doses of thyroxin (T4). The treatment significantly increased fatty acid mobilization in response to adrenaline over the levels observed in the control mice under all conditions studied. The activities of the high- and low-Km phosphodiesterases and of adenylate cyclase were also studied. Treatment of the ob/ob mice with T4 had little effect on the activities of the cyclic AMP phosphodiesterases (high and low Km) but it partially restored the activity of adenylate cyclase, which is deficient in these animals. A correlation was found in the T4-treated obese animals between the ability of the epididymal adipose tissue to mobilize fatty acids, its ability to increase the intracellular levels of cyclic AMP, and the activity of adenylate cyclase in response to adrenaline stimulation.", "contents": "Increased response of adipose tissue of the ob/ob mouse to the action of adrenaline after treatment with thyroxin. The activity of the lipolytic system of the obese hyperglycemic mouse was assessed after treatment with physiological doses of thyroxin (T4). The treatment significantly increased fatty acid mobilization in response to adrenaline over the levels observed in the control mice under all conditions studied. The activities of the high- and low-Km phosphodiesterases and of adenylate cyclase were also studied. Treatment of the ob/ob mice with T4 had little effect on the activities of the cyclic AMP phosphodiesterases (high and low Km) but it partially restored the activity of adenylate cyclase, which is deficient in these animals. A correlation was found in the T4-treated obese animals between the ability of the epididymal adipose tissue to mobilize fatty acids, its ability to increase the intracellular levels of cyclic AMP, and the activity of adenylate cyclase in response to adrenaline stimulation."}
{"id": "PMID:202381", "title": "A convenient method of establishing permanent lines of xeroderma pigmentosum cells.", "content": "Nine lymphoblastoid cell lines were established after transformation by Epstein-Barr virus of peripheral lymphocytes from four xeroderma pigmentosum (XP) patients, the parents of one XP patient, and three normal donors. All these cell lines proliferate as suspension in Roswell Park Memorial Institute Medium 1640 supplemented with 20% fetal bovine serum, without detectable release of infectious Epstein-Barr virus. Some characteristics of these cell lines, such as growth rates, chromosome numbers, UV sensitivities, and activities of unscheduled DNA syntheses induced by UV, 4-nitroquinoline 1-oxide, and N-methyl-N'-nitro-N-nitrosoguanidine, were determined. Results confirm that the properties related to XP are not altered by transformation with Epstein-Barr virus and are the same in degrees of defect as are those of dermal fibroblasts from the respective individuals. These XP and normal lymphoblastoid cell lines should be especially useful for biochemical studies on the mechanism of DNA repair, because they are easy to grow in mass culture.", "contents": "A convenient method of establishing permanent lines of xeroderma pigmentosum cells. Nine lymphoblastoid cell lines were established after transformation by Epstein-Barr virus of peripheral lymphocytes from four xeroderma pigmentosum (XP) patients, the parents of one XP patient, and three normal donors. All these cell lines proliferate as suspension in Roswell Park Memorial Institute Medium 1640 supplemented with 20% fetal bovine serum, without detectable release of infectious Epstein-Barr virus. Some characteristics of these cell lines, such as growth rates, chromosome numbers, UV sensitivities, and activities of unscheduled DNA syntheses induced by UV, 4-nitroquinoline 1-oxide, and N-methyl-N'-nitro-N-nitrosoguanidine, were determined. Results confirm that the properties related to XP are not altered by transformation with Epstein-Barr virus and are the same in degrees of defect as are those of dermal fibroblasts from the respective individuals. These XP and normal lymphoblastoid cell lines should be especially useful for biochemical studies on the mechanism of DNA repair, because they are easy to grow in mass culture."}
{"id": "PMID:202382", "title": "Induction of testicular sarcomas in Fischer rats by intratesticular injection of nickel subsulfide.", "content": "Nickel subsulfide (Ni3S2) was injected in various amounts into the testis of adult Fischer rats for the study of the acute and chronic effects of Ni3S2 on testicular cells. Rats given injections of 0.6 to 10 mg of Ni3S2 developed an immediate inflammatory response at the site of injection, followed by a delayed, slowly evolving coagulation necrosis of seminiferous tubules and interstitial cells. The extent of testicular necrosis was dose dependent, but at doses of 5 or 10 mg of Ni3S2 the rats invariably developed subtotal destruction of the testis. The testis became atrophic, without regeneration of seminiferous tubules. No damage was seen in the other testis, and no systemic effects were noted. Malignant testicular neoplasms developed in 16 of 19 rats within 20 months after an injection of 10 mg of Ni3S2. These neoplasms were classified by light and electron microscopy as fibrosarcomas, malignant fibrous histiocytomas, and rhabdomyosarcomas. None of the testicular neoplasms was derived from germ cells or genital cord cells. The occurrence of rhabdomyosarcomas in the testis, an organ normally devoid of striated muscle, suggests that Ni3S2 induces malignant transformation of undifferentiated, pluripotential mesenchymal cells.", "contents": "Induction of testicular sarcomas in Fischer rats by intratesticular injection of nickel subsulfide. Nickel subsulfide (Ni3S2) was injected in various amounts into the testis of adult Fischer rats for the study of the acute and chronic effects of Ni3S2 on testicular cells. Rats given injections of 0.6 to 10 mg of Ni3S2 developed an immediate inflammatory response at the site of injection, followed by a delayed, slowly evolving coagulation necrosis of seminiferous tubules and interstitial cells. The extent of testicular necrosis was dose dependent, but at doses of 5 or 10 mg of Ni3S2 the rats invariably developed subtotal destruction of the testis. The testis became atrophic, without regeneration of seminiferous tubules. No damage was seen in the other testis, and no systemic effects were noted. Malignant testicular neoplasms developed in 16 of 19 rats within 20 months after an injection of 10 mg of Ni3S2. These neoplasms were classified by light and electron microscopy as fibrosarcomas, malignant fibrous histiocytomas, and rhabdomyosarcomas. None of the testicular neoplasms was derived from germ cells or genital cord cells. The occurrence of rhabdomyosarcomas in the testis, an organ normally devoid of striated muscle, suggests that Ni3S2 induces malignant transformation of undifferentiated, pluripotential mesenchymal cells."}
{"id": "PMID:202384", "title": "Decreased alkaline phosphatase in cells transformed by rous sarcoma virus.", "content": "Chick embryo cells transformed by either of two strains of Rous sarcoma virus (Bryan high titer or Schmidt-Ruppin) have low levels of alkaline phosphatase activity compared with nontransformed chick embryo cells. Essentially no differences in acid phosphatase activity were observed between these transformed and nontransformed cells. A virus mutant, RSV-BH-Ta, induces temperature-dependent transformation in infected cells. At 41 degrees, the transformation-nonpermissive temperature, alkaline phosphatase activities were similar to those of chick embryo cells. Shifting these cells to 37 degrees resulted in a change to transformed morphology and a progressive loss of enzyme activity, requiring 18 to 24 hr to reach the level of transformed cells. Rat embryo cells transformed by murine sarcoma virus also contained lower alkaline phosphatase levels than did nontransformed cells. These observations suggest that decreased alkaline phosphatase activities may be a general property of transformed cells.", "contents": "Decreased alkaline phosphatase in cells transformed by rous sarcoma virus. Chick embryo cells transformed by either of two strains of Rous sarcoma virus (Bryan high titer or Schmidt-Ruppin) have low levels of alkaline phosphatase activity compared with nontransformed chick embryo cells. Essentially no differences in acid phosphatase activity were observed between these transformed and nontransformed cells. A virus mutant, RSV-BH-Ta, induces temperature-dependent transformation in infected cells. At 41 degrees, the transformation-nonpermissive temperature, alkaline phosphatase activities were similar to those of chick embryo cells. Shifting these cells to 37 degrees resulted in a change to transformed morphology and a progressive loss of enzyme activity, requiring 18 to 24 hr to reach the level of transformed cells. Rat embryo cells transformed by murine sarcoma virus also contained lower alkaline phosphatase levels than did nontransformed cells. These observations suggest that decreased alkaline phosphatase activities may be a general property of transformed cells."}
{"id": "PMID:202386", "title": "In vitro radiation response of cells from four human tumors propagated in immune-suppressed mice.", "content": "Two recently developed clonogenic assays for human tumor cells have been used to measure the in vitro radiation cell survival of four human tumors, a pancreatic carcinoma, a colonic carcinoma, an oat cell carcinoma of the lung, and a melanoma, propagated as xenografts in immune-suppressed mice. The slopes and shoulders of the survival curves for the first three tumors were all similar with Do's, respectively, of 94, 100, and 131 rads and with Dq's, respectively, of 8, 44, and 41 rads, However, melanoma cells from the fourth tumor had a survival curve that differed from those of the other three, both in having a wider shoulder with a Dq of 216 rads and in having a shallower slope with a Do value of 183 rads. It is suggested that the wide shoulder to the melanoma cell survival curve may in part explain the poor response to small fractionated doses of radiotherapy usually observed clinically for this tumor type. However, the data from the other three tumors suggest that differences in radiotherapeutic response seen in the clinic for these tumors cannot be attributed to differences in intrinsic radiosensitivity of the tumor cells.", "contents": "In vitro radiation response of cells from four human tumors propagated in immune-suppressed mice. Two recently developed clonogenic assays for human tumor cells have been used to measure the in vitro radiation cell survival of four human tumors, a pancreatic carcinoma, a colonic carcinoma, an oat cell carcinoma of the lung, and a melanoma, propagated as xenografts in immune-suppressed mice. The slopes and shoulders of the survival curves for the first three tumors were all similar with Do's, respectively, of 94, 100, and 131 rads and with Dq's, respectively, of 8, 44, and 41 rads, However, melanoma cells from the fourth tumor had a survival curve that differed from those of the other three, both in having a wider shoulder with a Dq of 216 rads and in having a shallower slope with a Do value of 183 rads. It is suggested that the wide shoulder to the melanoma cell survival curve may in part explain the poor response to small fractionated doses of radiotherapy usually observed clinically for this tumor type. However, the data from the other three tumors suggest that differences in radiotherapeutic response seen in the clinic for these tumors cannot be attributed to differences in intrinsic radiosensitivity of the tumor cells."}
{"id": "PMID:202387", "title": "Comparative ultrastructural studies of nucleoli of tumor cells treated with adriamycin and the newer anthracyclines, carminomycin and marcellomycin.", "content": "This study was designed to determine the effects of several antitimor anthracyclines, including Adriamycin and its analogs, carminomycin and marcellomycin, on the ultrastructure of nucleoli of Novikoff hepatoma cells. Adriamycin and carminomycin, which are structurally related, induce nucleolar segregation following the formation of conspicuous fibrillar centers. Marcellomycin did not induce formation of nucleolar fibrillar centers. Instead, numerous microspherules formed following treatment with marcellomycin; later complete nucleolar segregation developed. The microspherules were observed to be in various stages of extrusion from the nucleolar body. This microspherule \"migration\" appeared to be both time and drug concentration dependent. These results show that the rate and extent of nucleolar ultrastructural aberration may be related to structural differences of the various anthracyclines.", "contents": "Comparative ultrastructural studies of nucleoli of tumor cells treated with adriamycin and the newer anthracyclines, carminomycin and marcellomycin. This study was designed to determine the effects of several antitimor anthracyclines, including Adriamycin and its analogs, carminomycin and marcellomycin, on the ultrastructure of nucleoli of Novikoff hepatoma cells. Adriamycin and carminomycin, which are structurally related, induce nucleolar segregation following the formation of conspicuous fibrillar centers. Marcellomycin did not induce formation of nucleolar fibrillar centers. Instead, numerous microspherules formed following treatment with marcellomycin; later complete nucleolar segregation developed. The microspherules were observed to be in various stages of extrusion from the nucleolar body. This microspherule \"migration\" appeared to be both time and drug concentration dependent. These results show that the rate and extent of nucleolar ultrastructural aberration may be related to structural differences of the various anthracyclines."}
{"id": "PMID:202389", "title": "Electron-microscopic observations of normal coelomocytes from the earthworm, Lumbricus terrestris.", "content": "Coelomocytes of the earthworm, Lumbricus terrestris, were studied by transmission electron microscopy. Four morphological cell types are distinguishable: lymphocytic coelomocytes, granulocytic coelomocytes, eleocytes (chloragogen cells), and inclusion-containing coelomocytes. Within these major categories, several distinct cell types differ and may represent developmental stages. The two types of lymphocytic coelomocytes are small with central nuclei and scanty cytoplasms. Two types of granulocytic coelomocytes differ greatly in shape and content; both have small dark-staining granules that resemble lysosomes. Electrocytes, derived from chloragogen tissue, contain a variety of granules, inclusions and vacuoles. Inclusion-containing coelomocytes appear as two types which may be immature and mature forms. Although these cells resemble those that have been referred to as erythroid cells in other invertebrates, the large inclusion bodies are apparently unrelated to hemoglobin; they can undergo morphologic transformation and be extruded by exocytosis. This information on lymphocytic, granulocytic and inclusion-containing coelomocytes is crucial to understanding more about cellular immunity in the earthworm.", "contents": "Electron-microscopic observations of normal coelomocytes from the earthworm, Lumbricus terrestris. Coelomocytes of the earthworm, Lumbricus terrestris, were studied by transmission electron microscopy. Four morphological cell types are distinguishable: lymphocytic coelomocytes, granulocytic coelomocytes, eleocytes (chloragogen cells), and inclusion-containing coelomocytes. Within these major categories, several distinct cell types differ and may represent developmental stages. The two types of lymphocytic coelomocytes are small with central nuclei and scanty cytoplasms. Two types of granulocytic coelomocytes differ greatly in shape and content; both have small dark-staining granules that resemble lysosomes. Electrocytes, derived from chloragogen tissue, contain a variety of granules, inclusions and vacuoles. Inclusion-containing coelomocytes appear as two types which may be immature and mature forms. Although these cells resemble those that have been referred to as erythroid cells in other invertebrates, the large inclusion bodies are apparently unrelated to hemoglobin; they can undergo morphologic transformation and be extruded by exocytosis. This information on lymphocytic, granulocytic and inclusion-containing coelomocytes is crucial to understanding more about cellular immunity in the earthworm."}
{"id": "PMID:202394", "title": "Preferential association of newly synthesized histones with replicating SV40 DNA.", "content": "The assembly of newly synthesized histones into nucleosomes during replication of SV40 minichromosomes in vivo was studied. Infected cells were labeled with 35S-methionine for a time shorter than that required to complete a round of viral DNA replication. Mature and replicating SV40 minichromosomes were extracted and separated by zonal sedimentation, and their histone content was analyzed by polyacrylamide gel electrophoresis (SDS and acidic urea). We show that the pulse-labeled histones associate preferentially with the replicating DNA.", "contents": "Preferential association of newly synthesized histones with replicating SV40 DNA. The assembly of newly synthesized histones into nucleosomes during replication of SV40 minichromosomes in vivo was studied. Infected cells were labeled with 35S-methionine for a time shorter than that required to complete a round of viral DNA replication. Mature and replicating SV40 minichromosomes were extracted and separated by zonal sedimentation, and their histone content was analyzed by polyacrylamide gel electrophoresis (SDS and acidic urea). We show that the pulse-labeled histones associate preferentially with the replicating DNA."}
{"id": "PMID:202398", "title": "The binding site on SV40 DNA for a T antigen-related protein.", "content": "A protein closely related to SV40 T antigen was purified in a biologically active form from cells infected with the defective adenovirus-SV40 hybrid, Ad2+D2. This 107,000 dalton hybrid protein binds and protects a specific portion of SV40 DNA from digestion by pancreatic DNAase I. Hybridization, endonuclease cleavage and pyrimidine tract analysis of the protected fragments reveal that the D2 hybrid protein binds in a sequential manner to tandem recognition sites which lie within a sequence of 120 nucleotides at position 67 near the origin of SV40 replication.", "contents": "The binding site on SV40 DNA for a T antigen-related protein. A protein closely related to SV40 T antigen was purified in a biologically active form from cells infected with the defective adenovirus-SV40 hybrid, Ad2+D2. This 107,000 dalton hybrid protein binds and protects a specific portion of SV40 DNA from digestion by pancreatic DNAase I. Hybridization, endonuclease cleavage and pyrimidine tract analysis of the protected fragments reveal that the D2 hybrid protein binds in a sequential manner to tandem recognition sites which lie within a sequence of 120 nucleotides at position 67 near the origin of SV40 replication."}
{"id": "PMID:202400", "title": "Isolation and characterization of T antigen-negative revertants from a line of transformed rat cells containing one copy of the SV40 genome.", "content": "Negative selection with FUdR produced revertants from the transformed rat line 14B, which contains one insertion of the SV40 viral genome (Botchan, Topp and Sambrook, 1976). 14B contains nuclear T antigen, grows to a high density, grows in low serum and is anchorage-independent. The revertants fall into three classes with regard to viral DNA sequences: the SV40 DNA is retained; the SV40 DNA is retained but has undergone a deletion; and the SV40 DNA is lost, generating a cured cell. This heterogeneity is not a result of long-term passage. The revertants arise with a frequency of one in 8.4 X 10(5) cells after as few as 12 passages. All three classes of revertants are T antigen-negative, density-sensitive, more serum sensitive than 14B and anchorage-dependent. These data argue for a direct role of the functioning viral genome in the maintenance of the transformed state, and that with 14B, the phenotypes of transformation are not virus gene dosage-dependent.", "contents": "Isolation and characterization of T antigen-negative revertants from a line of transformed rat cells containing one copy of the SV40 genome. Negative selection with FUdR produced revertants from the transformed rat line 14B, which contains one insertion of the SV40 viral genome (Botchan, Topp and Sambrook, 1976). 14B contains nuclear T antigen, grows to a high density, grows in low serum and is anchorage-independent. The revertants fall into three classes with regard to viral DNA sequences: the SV40 DNA is retained; the SV40 DNA is retained but has undergone a deletion; and the SV40 DNA is lost, generating a cured cell. This heterogeneity is not a result of long-term passage. The revertants arise with a frequency of one in 8.4 X 10(5) cells after as few as 12 passages. All three classes of revertants are T antigen-negative, density-sensitive, more serum sensitive than 14B and anchorage-dependent. These data argue for a direct role of the functioning viral genome in the maintenance of the transformed state, and that with 14B, the phenotypes of transformation are not virus gene dosage-dependent."}
{"id": "PMID:202402", "title": "Implication of developmentally regulated Concanavalin A binding proteins of Dictyostelium in cell adhesion and cyclic AMP regulation.", "content": "Contact sites A and cyclic AMP phosphodiesterase are Concanavalin A binding membrane proteins. Both are characteristic for the aggregation phase of Dictyostelium discoideum. Extracellular cyclic AMP phosphodiesterase and an inhibitor of this enzyme can be recovered from the extracellular medium by binding to Concanavalin A-Sepharose.", "contents": "Implication of developmentally regulated Concanavalin A binding proteins of Dictyostelium in cell adhesion and cyclic AMP regulation. Contact sites A and cyclic AMP phosphodiesterase are Concanavalin A binding membrane proteins. Both are characteristic for the aggregation phase of Dictyostelium discoideum. Extracellular cyclic AMP phosphodiesterase and an inhibitor of this enzyme can be recovered from the extracellular medium by binding to Concanavalin A-Sepharose."}
{"id": "PMID:202410", "title": "[Histochemical and quantitative methods in the biopsy examination of skeletal muscles].", "content": "A complex bioptic examination of skeletal muscles as carried out in 280 excised samples has been subjected to a critical analysis. The examination suggested consists of histological and histochemical processing of native cryostat sections. Besides conventional staining methods the techniques recommended include the reaction for detection of myosin ATP-ase with and without acid preincubation, and reactions for NADH tertazolium reductase, acid phosphatase, nonspecific esterase, glycogen and lipids. Sections stained for ATP-ase are suitable for quantitative examinations such as assessing the diameters of muscle fibres.", "contents": "[Histochemical and quantitative methods in the biopsy examination of skeletal muscles]. A complex bioptic examination of skeletal muscles as carried out in 280 excised samples has been subjected to a critical analysis. The examination suggested consists of histological and histochemical processing of native cryostat sections. Besides conventional staining methods the techniques recommended include the reaction for detection of myosin ATP-ase with and without acid preincubation, and reactions for NADH tertazolium reductase, acid phosphatase, nonspecific esterase, glycogen and lipids. Sections stained for ATP-ase are suitable for quantitative examinations such as assessing the diameters of muscle fibres."}
{"id": "PMID:202411", "title": "Adriamycin stimulated superoxide formation in submitochondrial particles.", "content": "Adriamycin (doxorubicin), an anticancer agent, stimulated the formation of superoxide in submitochondrial particles isolated from bovine heart. Superoxide formation was detected by oxygen uptake, by the cooxidation of epinephrine to adrenochrome and by the reduction of acetylated cytochrome c. These processes were sensitive to superoxide dismutase (SOD). Rotenone-insensitive oxidation of NADH by the mitochondrial respiratory chain in the presence of oxygen caused the formation of approx 4 nmol of superoxide per min/mg of protein. Adriamycin at a concentration of 400 micron stimulated the rate of superoxide formation 6-fold to 25 nmol.min-1.mg-1, but this was not a maximum rate. Approximately 50 micron adriamycin was estimated to be sufficient for obtaining one-half maximal stimulation. Hydrogen peroxide accumulated as a final reaction product. Measurements of the relative catalase activity of blood-free tissues of rabbits and rats indicated that heart contained 2 to 4% of the catalase activity of liver or kidney. An enhanced production of superoxide and hydrogen peroxide and the relatively low catalase content of heart tissue may be factors in the cardiotoxicity induced by adriamycin chemotherapy if a similar reaction occurs in vivo.", "contents": "Adriamycin stimulated superoxide formation in submitochondrial particles. Adriamycin (doxorubicin), an anticancer agent, stimulated the formation of superoxide in submitochondrial particles isolated from bovine heart. Superoxide formation was detected by oxygen uptake, by the cooxidation of epinephrine to adrenochrome and by the reduction of acetylated cytochrome c. These processes were sensitive to superoxide dismutase (SOD). Rotenone-insensitive oxidation of NADH by the mitochondrial respiratory chain in the presence of oxygen caused the formation of approx 4 nmol of superoxide per min/mg of protein. Adriamycin at a concentration of 400 micron stimulated the rate of superoxide formation 6-fold to 25 nmol.min-1.mg-1, but this was not a maximum rate. Approximately 50 micron adriamycin was estimated to be sufficient for obtaining one-half maximal stimulation. Hydrogen peroxide accumulated as a final reaction product. Measurements of the relative catalase activity of blood-free tissues of rabbits and rats indicated that heart contained 2 to 4% of the catalase activity of liver or kidney. An enhanced production of superoxide and hydrogen peroxide and the relatively low catalase content of heart tissue may be factors in the cardiotoxicity induced by adriamycin chemotherapy if a similar reaction occurs in vivo."}
{"id": "PMID:202412", "title": "Protein composition of nuclear ribonucleoprotein particles isolated from liver of rats in the early stages of feeding of 3'-methyl-4-dimethylaminoazobenzene and from hepatoma induced by the same carcinogen.", "content": "The feeding of carcinogenic 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) in the early stages results in a change in the protein composition of the nuclear ribonucleoprotein particles of the rat liver. These particles are associated with newly synthesized RNA and it is assumed that they are involved in the processing and in the transport of this RNA. After 6 weeks of feeding of this azocarcinogen, the amount of one of the main polypeptides (apparent molecular weight 42 000) is decreased and after 10 weeks of feeding the particles are devoid of this polypeptide completely. Feeding of the non-carcinogenic p-aminoazobenzene (AB) is without any effect. The loss of this polypeptide is not characteristic for the malignant transformation. In the nuclear ribonucleoprotein particles isolated from hepatoma which has been induced by 3'-MeDAB this polypeptide is present in even higher proportion to other polypeptides than it is in particles isolated from liver cells of control animals. The 3'-MeDAB binds to the proteins of the liver nuclear ribonucleoprotein particles and interferes with the RNA processing. It is proposed that the changes in the composition of the protein moiety of the particles reflect changes in the population of liver cells leading finally to the selection of hepatoma cells which are resistant to the toxic effect of 3'-MeDAB on RNA processing.", "contents": "Protein composition of nuclear ribonucleoprotein particles isolated from liver of rats in the early stages of feeding of 3'-methyl-4-dimethylaminoazobenzene and from hepatoma induced by the same carcinogen. The feeding of carcinogenic 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) in the early stages results in a change in the protein composition of the nuclear ribonucleoprotein particles of the rat liver. These particles are associated with newly synthesized RNA and it is assumed that they are involved in the processing and in the transport of this RNA. After 6 weeks of feeding of this azocarcinogen, the amount of one of the main polypeptides (apparent molecular weight 42 000) is decreased and after 10 weeks of feeding the particles are devoid of this polypeptide completely. Feeding of the non-carcinogenic p-aminoazobenzene (AB) is without any effect. The loss of this polypeptide is not characteristic for the malignant transformation. In the nuclear ribonucleoprotein particles isolated from hepatoma which has been induced by 3'-MeDAB this polypeptide is present in even higher proportion to other polypeptides than it is in particles isolated from liver cells of control animals. The 3'-MeDAB binds to the proteins of the liver nuclear ribonucleoprotein particles and interferes with the RNA processing. It is proposed that the changes in the composition of the protein moiety of the particles reflect changes in the population of liver cells leading finally to the selection of hepatoma cells which are resistant to the toxic effect of 3'-MeDAB on RNA processing."}
{"id": "PMID:202413", "title": "Guanosine 3',5'-monophosphate and the action of alkylating agents.", "content": "The intracellular level of guanosine 3',5'-monophosphate (cGMP) has been measured in Walker carcinoma cells in tissue culture after treatment with various alkylating agents. At concentrations which caused a rise in the level of adenosine 3',5'-monophosphate (cAMP) chlorambucil and 5-(1-aziridinyl)-2,4-dinitrobenzamide (CB 1954) produced only a small (35%) elevation of cGMP, while merophan had no such effect. This suggests that any effect of cAMP will not be outweighed by an equivalent rise in cGMP. Sepcific cytosolic binding of cGMP decreased with increasing resistance of Walker cells to alkylating agents, while the dissociation constant, KD, for binding increased. This was also observed with cAMP binding which suggests that the same protein in responsible for binding both nucleotides.", "contents": "Guanosine 3',5'-monophosphate and the action of alkylating agents. The intracellular level of guanosine 3',5'-monophosphate (cGMP) has been measured in Walker carcinoma cells in tissue culture after treatment with various alkylating agents. At concentrations which caused a rise in the level of adenosine 3',5'-monophosphate (cAMP) chlorambucil and 5-(1-aziridinyl)-2,4-dinitrobenzamide (CB 1954) produced only a small (35%) elevation of cGMP, while merophan had no such effect. This suggests that any effect of cAMP will not be outweighed by an equivalent rise in cGMP. Sepcific cytosolic binding of cGMP decreased with increasing resistance of Walker cells to alkylating agents, while the dissociation constant, KD, for binding increased. This was also observed with cAMP binding which suggests that the same protein in responsible for binding both nucleotides."}
{"id": "PMID:202416", "title": "Persistence of enteroviruses in sewage sludge.", "content": "Sewage from residential areas often contains viruses pathogenic for man and significant amounts are probably associated with solids in sewage sludge. Information on the survival of viruses in sewage sludge is necessary in order to develop guidelines for recycling programmes that involve spreading the sludge on land. In the present study, a number of enteroviruses were added to sewage sludge and the artificially contaminated sludges were tested for viruses at intervals over a 12-week period. Most of the viruses survived for many weeks at room temperature. It is clear that sewage sludge destined for land application should be adequately treated for virus inactivation. In interpreting these results, it should be borne in mind that the survival of hepatitis A virus might be similar. Recent reports about the reappearance of poliomyelitis in regions with immunization programmes should also be taken into consideration.", "contents": "Persistence of enteroviruses in sewage sludge. Sewage from residential areas often contains viruses pathogenic for man and significant amounts are probably associated with solids in sewage sludge. Information on the survival of viruses in sewage sludge is necessary in order to develop guidelines for recycling programmes that involve spreading the sludge on land. In the present study, a number of enteroviruses were added to sewage sludge and the artificially contaminated sludges were tested for viruses at intervals over a 12-week period. Most of the viruses survived for many weeks at room temperature. It is clear that sewage sludge destined for land application should be adequately treated for virus inactivation. In interpreting these results, it should be borne in mind that the survival of hepatitis A virus might be similar. Recent reports about the reappearance of poliomyelitis in regions with immunization programmes should also be taken into consideration."}
{"id": "PMID:202417", "title": "Poliomyelitis: epidemiology and prophylaxis. 4. Serological and virological surveys conducted after a mass vaccination campaign for the control of a threatening poliomyelitis epidemic.", "content": "In 1973, a type 1 poliomyelitis epidemic in Kenya was curtailed at an early stage by two mass distributions of trivalent oral vaccine. It was considered useful to know the immunity status of the child population that had resulted from the vaccine distributions and that had presumably contributed to its control. We also wished to know to what extent wild and vaccine virus strains were in circulation after the mass vaccination campaign. Anal swabs and blood were collected from a sample of the children in four areas where the efficiency of vaccine distribution had varied, and the results of virus isolation attempts and antibody tests are reported. Three poliovirus strains were isolated. It was surprising that, in general, the herd immunity after two vaccination rounds did not substantially differ from that found in Kenya on other occasions. Possible reasons for these results are discussed.", "contents": "Poliomyelitis: epidemiology and prophylaxis. 4. Serological and virological surveys conducted after a mass vaccination campaign for the control of a threatening poliomyelitis epidemic. In 1973, a type 1 poliomyelitis epidemic in Kenya was curtailed at an early stage by two mass distributions of trivalent oral vaccine. It was considered useful to know the immunity status of the child population that had resulted from the vaccine distributions and that had presumably contributed to its control. We also wished to know to what extent wild and vaccine virus strains were in circulation after the mass vaccination campaign. Anal swabs and blood were collected from a sample of the children in four areas where the efficiency of vaccine distribution had varied, and the results of virus isolation attempts and antibody tests are reported. Three poliovirus strains were isolated. It was surprising that, in general, the herd immunity after two vaccination rounds did not substantially differ from that found in Kenya on other occasions. Possible reasons for these results are discussed."}
{"id": "PMID:202418", "title": "Poliomyelitis: epidemiology and prophylaxis. 5. Results of a two- and three-dose vaccination experiment.", "content": "In tropical countries, seroconversion rates following oral poliomyelitis vaccination are frequently unsatisfactory. In an area of the Machakos district in Kenya, 4000 children under 5 years of age have been registered and are visited fortnightly by trained field staff as part of a comprehensive, population-based, longitudinal surveillance project. It was considered possible that poliomyelitis vaccine, given orally to children twice or three times at home, would produce satisfactory conversion rates. After collection of blood from a random sample of the children, vaccine was given twice to all children under 5 years of age. Blood was then collected a second time from a different sample of children. After a third dose of vaccine, a third blood collection followed. The percentages of the children that received vaccine each round were calculated and the sera tested for antibodies. It appeared that the mean titre was more strongly related to age than to the number of doses of poliomyelitis vaccine received. Improvement of herd immunity after two vaccine distributions was significant for a few age groups and for two types of vaccine only. In none of the groups was a significant improvement obtained by the third vaccine distribution. The problems associated with vaccination by live poliomyelitis vaccine in tropical countries are discussed in relation to the results.", "contents": "Poliomyelitis: epidemiology and prophylaxis. 5. Results of a two- and three-dose vaccination experiment. In tropical countries, seroconversion rates following oral poliomyelitis vaccination are frequently unsatisfactory. In an area of the Machakos district in Kenya, 4000 children under 5 years of age have been registered and are visited fortnightly by trained field staff as part of a comprehensive, population-based, longitudinal surveillance project. It was considered possible that poliomyelitis vaccine, given orally to children twice or three times at home, would produce satisfactory conversion rates. After collection of blood from a random sample of the children, vaccine was given twice to all children under 5 years of age. Blood was then collected a second time from a different sample of children. After a third dose of vaccine, a third blood collection followed. The percentages of the children that received vaccine each round were calculated and the sera tested for antibodies. It appeared that the mean titre was more strongly related to age than to the number of doses of poliomyelitis vaccine received. Improvement of herd immunity after two vaccine distributions was significant for a few age groups and for two types of vaccine only. In none of the groups was a significant improvement obtained by the third vaccine distribution. The problems associated with vaccination by live poliomyelitis vaccine in tropical countries are discussed in relation to the results."}
{"id": "PMID:202419", "title": "[Tumor induction in mice treated with hydrocortisone and innoculated with polyoma transformed hamster cells].", "content": "Tumors have been induced in hydrocortisone treated Mice innoculated with wild-type polyoma transformed Hamster cells. The filtrate from these tumors infects Mouse embryo cells and induces the production of polyoma virus. The polyoma virus has been characterised in the infected cells with anti-polyoma capsid serum.", "contents": "[Tumor induction in mice treated with hydrocortisone and innoculated with polyoma transformed hamster cells]. Tumors have been induced in hydrocortisone treated Mice innoculated with wild-type polyoma transformed Hamster cells. The filtrate from these tumors infects Mouse embryo cells and induces the production of polyoma virus. The polyoma virus has been characterised in the infected cells with anti-polyoma capsid serum."}
{"id": "PMID:202420", "title": "A novel alkaline phosphatase, a minor component of normal liver phosphatases.", "content": "A novel alkaline phosphatase differing from the so-called liver-specific isoenzyme was found in four out of twenty-four normal adult livers. Although the mobility of this enzyme was the same as that of so-called liver-specific alkaline phosphatase on the polyacrylamide gel electrophoretogram, its mobility was not altered following neuraminidase treatment, while that of the liver-specific enzyme was affected by the same treatment. Both enzymes also differed in other enzymatic and immunologic properties. The enzyme, however, resembled the so-called intestinal alkaline phosphatase in many enzymatic and immunologic properties. Thus, the inhibition patterns by amino acids, EDTA and inorganic phosphate, the pH optima, KM values for phenyl phosphate and reactivity with anti-intestinal alkaline phosphatase antibody were quite similar for both enzymes. Differences in the properties of this enzyme and intestinal alkaline phosphatase were in sensitivity to denaturation by treatment with heat and urea and to inhibition by Levamisole. The possible origin of the enzyme in normal liver and its relationship to the Kasahara isoenzyme and fetal intestine-type in hepatoma is discussed.", "contents": "A novel alkaline phosphatase, a minor component of normal liver phosphatases. A novel alkaline phosphatase differing from the so-called liver-specific isoenzyme was found in four out of twenty-four normal adult livers. Although the mobility of this enzyme was the same as that of so-called liver-specific alkaline phosphatase on the polyacrylamide gel electrophoretogram, its mobility was not altered following neuraminidase treatment, while that of the liver-specific enzyme was affected by the same treatment. Both enzymes also differed in other enzymatic and immunologic properties. The enzyme, however, resembled the so-called intestinal alkaline phosphatase in many enzymatic and immunologic properties. Thus, the inhibition patterns by amino acids, EDTA and inorganic phosphate, the pH optima, KM values for phenyl phosphate and reactivity with anti-intestinal alkaline phosphatase antibody were quite similar for both enzymes. Differences in the properties of this enzyme and intestinal alkaline phosphatase were in sensitivity to denaturation by treatment with heat and urea and to inhibition by Levamisole. The possible origin of the enzyme in normal liver and its relationship to the Kasahara isoenzyme and fetal intestine-type in hepatoma is discussed."}
{"id": "PMID:202421", "title": "Effect of clofibrate on the composition of very low and low density lipoprotein subfractions in type III hyperlipoproteinaemia.", "content": "The effect of clofibrate on the lipid and protein composition of very low and low density lipoprotein subfractions (VLDL of SF greater than 100, 60-100 and 20-60; LDL of Sf 10.4-20, 5.7-12 and 3.5-6.5), was investigated in 6 patients with type III hyperlipoproteinaemia (HLP). After four weeks of therapy significant reductions occurred in the concentration of cholesterol in each VLDL fraction, and of triglycerides in Sf greater than 100 and Sf 60-100 VLDL. No changes were found in the concentrations of apolipoprotein B or of the total tetramethylurea (TMU) soluble proteins, but in four patients in whom polyacrylamide disc gel electrophoresis of the TMU soluble proteins was carried out, it was found that arginine-rich peptide (ARP) had largely disappeared on therapy. These findings would be in keeping with increased catabolism of VLDL in response to clofibrate. No significant changes were observed in LDL lipid or protein concentrations.", "contents": "Effect of clofibrate on the composition of very low and low density lipoprotein subfractions in type III hyperlipoproteinaemia. The effect of clofibrate on the lipid and protein composition of very low and low density lipoprotein subfractions (VLDL of SF greater than 100, 60-100 and 20-60; LDL of Sf 10.4-20, 5.7-12 and 3.5-6.5), was investigated in 6 patients with type III hyperlipoproteinaemia (HLP). After four weeks of therapy significant reductions occurred in the concentration of cholesterol in each VLDL fraction, and of triglycerides in Sf greater than 100 and Sf 60-100 VLDL. No changes were found in the concentrations of apolipoprotein B or of the total tetramethylurea (TMU) soluble proteins, but in four patients in whom polyacrylamide disc gel electrophoresis of the TMU soluble proteins was carried out, it was found that arginine-rich peptide (ARP) had largely disappeared on therapy. These findings would be in keeping with increased catabolism of VLDL in response to clofibrate. No significant changes were observed in LDL lipid or protein concentrations."}
{"id": "PMID:202422", "title": "Membrane-bound arylamidase from human hepatoma cells having the same electrophoretic mobility as placental membrane-bound arylamidase.", "content": "A membrane-bound arylamidase from well-differentiated hepatocellular carcinoma having the same electrophoretic mobility as placental membrane-bound arylamidase was found. The enzyme was found to be a sialoprotein and was activated by Co2+. Hepatoma membrane-bound arylamidase had a similar molecular weight (240 000) and kinetic properties to normal liver membrane-bound arylamidase, but differed from the liver enzyme with respect to electrophoretic mobility, heat stability and urea inactivation.", "contents": "Membrane-bound arylamidase from human hepatoma cells having the same electrophoretic mobility as placental membrane-bound arylamidase. A membrane-bound arylamidase from well-differentiated hepatocellular carcinoma having the same electrophoretic mobility as placental membrane-bound arylamidase was found. The enzyme was found to be a sialoprotein and was activated by Co2+. Hepatoma membrane-bound arylamidase had a similar molecular weight (240 000) and kinetic properties to normal liver membrane-bound arylamidase, but differed from the liver enzyme with respect to electrophoretic mobility, heat stability and urea inactivation."}
{"id": "PMID:202423", "title": "Femoral neuropathy associated with anticoagulant therapy.", "content": "The English literature concerning femoral neuropathy associated with anticoagulant therapy is reviewed. Anatomical dissections were carried out in order to determine how the neuropathy might be produced. It is postulated that hemorrhage occurs within the iliacus muscle and that a pressure neuropathy of the femoral nerve ensues. Conservative management is recommended. The condition is probably more prevalent than previously thought, as evidenced by the fact that two cases were diagnosed in as many years by one orthopedic surgeon in a 300-bed general hospital.", "contents": "Femoral neuropathy associated with anticoagulant therapy. The English literature concerning femoral neuropathy associated with anticoagulant therapy is reviewed. Anatomical dissections were carried out in order to determine how the neuropathy might be produced. It is postulated that hemorrhage occurs within the iliacus muscle and that a pressure neuropathy of the femoral nerve ensues. Conservative management is recommended. The condition is probably more prevalent than previously thought, as evidenced by the fact that two cases were diagnosed in as many years by one orthopedic surgeon in a 300-bed general hospital."}
{"id": "PMID:202424", "title": "Epiphyseal cartilage cAMP changes produced by electrical and mechanical perturbations.", "content": "Epiphyseal cartilage from chick embryo was subjected in vitro for one to 15 minutes to static compressive forces or oscillating electric fields. The same stimuli were applied to suspensions of cells isolated from the epiphyses. At the end of the perturbation cAMP was measured in the tissue or cell extracts by radioimmunoassay. It was found that a physiological (60 g/cm2) static pressure reduced the cAMP content in the tissue and the separated cells. An oscillating electric field above 900 V/1.5 cm, 5Hz, enhanced the cAMP accumulation in the intact tissue. This effect was produced only when the long axis of the bones was oriented parallel to the electric field. In isolated cells an electric field above 750 V/1.5 cm, 5Hz, caused a decrease in cAMP content. Charged matrix macromolecules and orientation of the cells within the cell matrix may have a modulating effect on the initiation of this response. It is postulated that the change in cAMP is the early cellular signal in the response to an electrical or mechanical perturbation which leads to bone remodeling.", "contents": "Epiphyseal cartilage cAMP changes produced by electrical and mechanical perturbations. Epiphyseal cartilage from chick embryo was subjected in vitro for one to 15 minutes to static compressive forces or oscillating electric fields. The same stimuli were applied to suspensions of cells isolated from the epiphyses. At the end of the perturbation cAMP was measured in the tissue or cell extracts by radioimmunoassay. It was found that a physiological (60 g/cm2) static pressure reduced the cAMP content in the tissue and the separated cells. An oscillating electric field above 900 V/1.5 cm, 5Hz, enhanced the cAMP accumulation in the intact tissue. This effect was produced only when the long axis of the bones was oriented parallel to the electric field. In isolated cells an electric field above 750 V/1.5 cm, 5Hz, caused a decrease in cAMP content. Charged matrix macromolecules and orientation of the cells within the cell matrix may have a modulating effect on the initiation of this response. It is postulated that the change in cAMP is the early cellular signal in the response to an electrical or mechanical perturbation which leads to bone remodeling."}
{"id": "PMID:202426", "title": "Irradiation induced kyphosis.", "content": "Eighty-one patients with Wilms tumor treated by irradiation and chemotherapy were studied. Despite the fact that multiple portals for irradiation were used, each crossing the midline, the amount of irradiation delivered to different parts of the vertebral body varied and it was this variation in delivered dose which produced axial skeletal deformities in 70% of the patients. Of the 57 patients with these deformities 32 had scoliosis, 22 kyphoscoliosis and 3 patients pure kyphosis; 12 patients had a kyphotic deformity of over 25 degrees, 7 patients requiring surgical correction. A high incidence of pseudarthrosis following posterior fusion has led to the preference of a 2-stage procedure, anterior interbody fusion followed by a posterior fusion with Harrington rods after 2 weeks of correction in halo femoral traction.", "contents": "Irradiation induced kyphosis. Eighty-one patients with Wilms tumor treated by irradiation and chemotherapy were studied. Despite the fact that multiple portals for irradiation were used, each crossing the midline, the amount of irradiation delivered to different parts of the vertebral body varied and it was this variation in delivered dose which produced axial skeletal deformities in 70% of the patients. Of the 57 patients with these deformities 32 had scoliosis, 22 kyphoscoliosis and 3 patients pure kyphosis; 12 patients had a kyphotic deformity of over 25 degrees, 7 patients requiring surgical correction. A high incidence of pseudarthrosis following posterior fusion has led to the preference of a 2-stage procedure, anterior interbody fusion followed by a posterior fusion with Harrington rods after 2 weeks of correction in halo femoral traction."}
{"id": "PMID:202430", "title": "Effects of renal dopamine receptor and beta-adrenoreceptor blockade on rises in blood angiotensin after haemorrhage, renal ischaemia and frusemide diuresis in the dog.", "content": "1. In chloralose-anaesthetized dogs, central venous and arterial angiotensin (AII) levels were monitored by blood-bathed bioassay during venous haemorrhage of 20 ml/kg, acute renal ischaemia induced by suprarenal aortic stenosis and frusemide-induced diuresis. 2. Blockade of intrarenal dopamine receptors with ergometrine reduced markedly the increments in arterial AII associated with haemorrhage or suprarenal aortic stenosis, but did not consistently affect the corresponding increments in venous AII. 3. Ergometrine or renal denervation did not affect the increases of blood AII associated with frusemide diuresis. 4. Blockade of beta-adrenoreceptors with propranolol, by contrast, reduced blood AII increments associated with all three procedures. 5. It is suggested that renin release during moderate haemorrhage and acute suprarenal aortic stenosis is, in the dog, partly due to activation of intrarenal dopaminergic nerves. 6. The possibility is discussed that propranolol may depress renin release in the dog by an action other than that of blocking beta-adrenoreceptors.", "contents": "Effects of renal dopamine receptor and beta-adrenoreceptor blockade on rises in blood angiotensin after haemorrhage, renal ischaemia and frusemide diuresis in the dog. 1. In chloralose-anaesthetized dogs, central venous and arterial angiotensin (AII) levels were monitored by blood-bathed bioassay during venous haemorrhage of 20 ml/kg, acute renal ischaemia induced by suprarenal aortic stenosis and frusemide-induced diuresis. 2. Blockade of intrarenal dopamine receptors with ergometrine reduced markedly the increments in arterial AII associated with haemorrhage or suprarenal aortic stenosis, but did not consistently affect the corresponding increments in venous AII. 3. Ergometrine or renal denervation did not affect the increases of blood AII associated with frusemide diuresis. 4. Blockade of beta-adrenoreceptors with propranolol, by contrast, reduced blood AII increments associated with all three procedures. 5. It is suggested that renin release during moderate haemorrhage and acute suprarenal aortic stenosis is, in the dog, partly due to activation of intrarenal dopaminergic nerves. 6. The possibility is discussed that propranolol may depress renin release in the dog by an action other than that of blocking beta-adrenoreceptors."}
{"id": "PMID:202425", "title": "Pyrophosphate levels and magnesium oxide therapy in osteogenesis imperfecta.", "content": "Serum pyrophosphate levels were determined in 52 patients with osteogenesis imperfecta. In 19 patients the levels were increased, in 14 normal and in 19 fluctuated. No correlation with disease severity was evident. By a double blind study it was shown that neither the administration of oral magnesium oxide, nor placebo, affected the serum pyrophosphate level or the clinical course.", "contents": "Pyrophosphate levels and magnesium oxide therapy in osteogenesis imperfecta. Serum pyrophosphate levels were determined in 52 patients with osteogenesis imperfecta. In 19 patients the levels were increased, in 14 normal and in 19 fluctuated. No correlation with disease severity was evident. By a double blind study it was shown that neither the administration of oral magnesium oxide, nor placebo, affected the serum pyrophosphate level or the clinical course."}
{"id": "PMID:202431", "title": "Insomnia and the physiology of sleep.", "content": "Sleep is a vital human physiologic process. Insomnia can be caused by obsession and depression states, pain, or worry over everyday problems. Because of their pharmacologic action, alcohol and high doses of soporifics used as remedies may produce REM-deficit sleep and actually prolong insomnia. If the true cause of sleeplessness is not recognized and properly treated, insomnia may develop into a severe sleep problem. Since benzodiazepines and chloral hydrate do not suppress REM sleep, they are the medications of choice in the therapy for insomnia.", "contents": "Insomnia and the physiology of sleep. Sleep is a vital human physiologic process. Insomnia can be caused by obsession and depression states, pain, or worry over everyday problems. Because of their pharmacologic action, alcohol and high doses of soporifics used as remedies may produce REM-deficit sleep and actually prolong insomnia. If the true cause of sleeplessness is not recognized and properly treated, insomnia may develop into a severe sleep problem. Since benzodiazepines and chloral hydrate do not suppress REM sleep, they are the medications of choice in the therapy for insomnia."}
{"id": "PMID:202432", "title": "Biochemical background of atherosclerotic heart lesion in an experiment.", "content": "The authors investigated enzymic systems and corresponding substrate cycles that transport hydrogen across the mitochondrial membrane in a myocardium with experimental cholesterol-induced atherosclerosis. Sensitive spectrophotometric methods were used for assessing the activities of cytoplasmic and mitochondrial enzymes: lactate and alpha-glycerphosphate dehydrogenases, and of characteristic mitochondrial enzymes: glutamate and beta-hydroxybutyrate dehydrogenases. Specific enzymological methods were used in determining the concentrations of lactic, pyruvic, glycerophosphoric, dihydroacetonephosphoric, malic, oxaloacetic, glutamic, alpha-ketoglutaric, acetoacetic, and beta-hydroxybutyric acids. The cytoplasmic NAD/NADH quotient was calculated. The investigators found a reduction of enzymic activities in the \"shuttle\" transport system studied, marked deviations from normal levels of their substrates, and a reduction of the NAD/NADH quotient by the factor 0.56. All these phenomena represent a biochemical background of a complex of symptoms characterizing severe myocardial lesion in experimental atherosclerosis.", "contents": "Biochemical background of atherosclerotic heart lesion in an experiment. The authors investigated enzymic systems and corresponding substrate cycles that transport hydrogen across the mitochondrial membrane in a myocardium with experimental cholesterol-induced atherosclerosis. Sensitive spectrophotometric methods were used for assessing the activities of cytoplasmic and mitochondrial enzymes: lactate and alpha-glycerphosphate dehydrogenases, and of characteristic mitochondrial enzymes: glutamate and beta-hydroxybutyrate dehydrogenases. Specific enzymological methods were used in determining the concentrations of lactic, pyruvic, glycerophosphoric, dihydroacetonephosphoric, malic, oxaloacetic, glutamic, alpha-ketoglutaric, acetoacetic, and beta-hydroxybutyric acids. The cytoplasmic NAD/NADH quotient was calculated. The investigators found a reduction of enzymic activities in the \"shuttle\" transport system studied, marked deviations from normal levels of their substrates, and a reduction of the NAD/NADH quotient by the factor 0.56. All these phenomena represent a biochemical background of a complex of symptoms characterizing severe myocardial lesion in experimental atherosclerosis."}
{"id": "PMID:202436", "title": "Serum lipids in angiographically assessed coronary atherosclerosis.", "content": "Cholesterol, triglycerides, and Lp(a)/pre-beta1 lipoprotein were analyzed in 153 patients typed for liproprotien patterns. Coronary atherosclerosis was determined by selective coronary angiography and graded by a system taking into account proximal, middle and distal segments. Smoking habits, family history and hypertension were also recorded. Normal coronary arteries were encountered in 45, moderate coronary atherosclerosis (less than median score) in 50, and severe changes (greater than median score) in 58 patients. Cholesterol (P less than 0.05), positivity of Lp (a)/pre-beta1 lipoprotein (P less than 0.01), a family history of coronary heart disease (P less than 0.05), and smoking (P less than 0.01) differed between the group of normal arteries and the whole group of luminal obstructions. Serum triglycerides were not associated with coronary atherosclerosis. Cholesterol, positivity of the Lp(a)/pre-beta1 lipoprotein and a family history of coronary heart disease were also associated with the severity of the disease. Smoking was less prevalent in the group with severe changes.", "contents": "Serum lipids in angiographically assessed coronary atherosclerosis. Cholesterol, triglycerides, and Lp(a)/pre-beta1 lipoprotein were analyzed in 153 patients typed for liproprotien patterns. Coronary atherosclerosis was determined by selective coronary angiography and graded by a system taking into account proximal, middle and distal segments. Smoking habits, family history and hypertension were also recorded. Normal coronary arteries were encountered in 45, moderate coronary atherosclerosis (less than median score) in 50, and severe changes (greater than median score) in 58 patients. Cholesterol (P less than 0.05), positivity of Lp (a)/pre-beta1 lipoprotein (P less than 0.01), a family history of coronary heart disease (P less than 0.05), and smoking (P less than 0.01) differed between the group of normal arteries and the whole group of luminal obstructions. Serum triglycerides were not associated with coronary atherosclerosis. Cholesterol, positivity of the Lp(a)/pre-beta1 lipoprotein and a family history of coronary heart disease were also associated with the severity of the disease. Smoking was less prevalent in the group with severe changes."}
{"id": "PMID:202439", "title": "Patterns of cyclic 3'5'-adenosine monophosphate excretion in parathyroid dysfunction.", "content": "The pattern of excretion of cyclic 3'5' adenosine monophosphate (cAMP) over 24 h was evaluated in nine hyperparathyroid, four hypoparathyroid and three postoperative hyperparathyroid patients. The hyperparathyroid patients had increased excretion at the time of the normal nadir and were normal or low occasionally during the day. The pattern in the hypoparathyroid and in the postoperative patients also differed from normal. These findings suggest that both peaks of urinary cAMP excretion found in normal individuals result from the effects of parathyroid hormone on the kidneys.", "contents": "Patterns of cyclic 3'5'-adenosine monophosphate excretion in parathyroid dysfunction. The pattern of excretion of cyclic 3'5' adenosine monophosphate (cAMP) over 24 h was evaluated in nine hyperparathyroid, four hypoparathyroid and three postoperative hyperparathyroid patients. The hyperparathyroid patients had increased excretion at the time of the normal nadir and were normal or low occasionally during the day. The pattern in the hypoparathyroid and in the postoperative patients also differed from normal. These findings suggest that both peaks of urinary cAMP excretion found in normal individuals result from the effects of parathyroid hormone on the kidneys."}
{"id": "PMID:202440", "title": "Iron, zinc, free radicals and oxygen in tissue disorders and cancer control.", "content": "Evidence is presented supporting the argument that various tissue disorders are the result of iron becoming decompartmentalized. In healthy cells, vital molecules are protected from the action of decompartmentalized iron by the presence of zinc. This protection is particularly important during processes leading to cell division. Should excessive decompartmentalization occur and this protective mechanism become overloaded or should it be weakened by ill health, damaging oxidative free-radical reactions may take place. If these are extensive, death may result. When they are only limited, possibly owing to a low oxygen tension or the presence of copper or a carcinogen, the cell may survive but cancer may result. This 'antioxidant' theory of cancer may provide a unifying mechanism for the action of many carcinogenic agents. Carcinogens are considered to be activated not only by the more usually accepted enzymic pathways but by free-radical reactions, catalysed by iron, in the vicinity of critical sites.", "contents": "Iron, zinc, free radicals and oxygen in tissue disorders and cancer control. Evidence is presented supporting the argument that various tissue disorders are the result of iron becoming decompartmentalized. In healthy cells, vital molecules are protected from the action of decompartmentalized iron by the presence of zinc. This protection is particularly important during processes leading to cell division. Should excessive decompartmentalization occur and this protective mechanism become overloaded or should it be weakened by ill health, damaging oxidative free-radical reactions may take place. If these are extensive, death may result. When they are only limited, possibly owing to a low oxygen tension or the presence of copper or a carcinogen, the cell may survive but cancer may result. This 'antioxidant' theory of cancer may provide a unifying mechanism for the action of many carcinogenic agents. Carcinogens are considered to be activated not only by the more usually accepted enzymic pathways but by free-radical reactions, catalysed by iron, in the vicinity of critical sites."}
{"id": "PMID:202447", "title": "Environmental effects on the central nervous system.", "content": "The central nervous system (CNS) is designed to respond to the environment and is peculiarly vulnerable to many of the influences found in the environment. Utilizing an anatomical classification (cortex, cerebellum, peripheral nerves) major toxins and stresses are reviewed with selections from recent references. Selective vulnerability of certain areas to particular toxins is apparent at all levels of the CNS, although the amount of damage produced by any noxious agent depends on the age and genetic substrate of the subject. It is apparent that the effects of certain well known and long respected environmental toxins such as lead, mercury, etc., deserve continued surveillance. In addition, the overwhelming impact on the CNS of social damages such as trauma, alcohol, and tobacco cannot be ignored by environmentalists. The effect of the hospital and therapeutic environment has become apparent in view of increased awareness of iatrogenic disorders. The need for particular laboratory tests, for example, examination of CSF and nerve conduction toxicity studies, is suggested. Epidemics such as the recent solvent neuropathies suggest a need for continued animal studies that are chronic, as well as acute evaluations when predicting the potential toxic effects of industrial compounds.", "contents": "Environmental effects on the central nervous system. The central nervous system (CNS) is designed to respond to the environment and is peculiarly vulnerable to many of the influences found in the environment. Utilizing an anatomical classification (cortex, cerebellum, peripheral nerves) major toxins and stresses are reviewed with selections from recent references. Selective vulnerability of certain areas to particular toxins is apparent at all levels of the CNS, although the amount of damage produced by any noxious agent depends on the age and genetic substrate of the subject. It is apparent that the effects of certain well known and long respected environmental toxins such as lead, mercury, etc., deserve continued surveillance. In addition, the overwhelming impact on the CNS of social damages such as trauma, alcohol, and tobacco cannot be ignored by environmentalists. The effect of the hospital and therapeutic environment has become apparent in view of increased awareness of iatrogenic disorders. The need for particular laboratory tests, for example, examination of CSF and nerve conduction toxicity studies, is suggested. Epidemics such as the recent solvent neuropathies suggest a need for continued animal studies that are chronic, as well as acute evaluations when predicting the potential toxic effects of industrial compounds."}
{"id": "PMID:202452", "title": "Effect of isometric exercise on catecholamines in the coronary circulation.", "content": "Arterial and coronary sinus blood levels of catecholamines, adenosine 3', 5'-cyclic monophosphate (c-AMP) and lactate were measured during isometric exercise in fourteen patients. In no patient did lactate production occur. Mean resting total catecholamine levels both arterial (0.53 +/- 0.07 ng/ml; 2.94 +/- 0.38 nmol/l) and coronary sinus (0.4 +/- 0.08 ng/ml; 2.22 +/- 0.44 nmol/l), did not change significantly on exercise. Coronary sinus c-AMP levels fell on exercise from 11.5 +/- 0.8 nmol/l (resting) to 9.9 +/- 0.8 nmol/l (exercise) (P less than 0.01) with an arterial-coronary sinus difference of 1.2 nmol/l (P less than 0.01) on exercise. Our findings suggest that isometric exercise does not normally result in excessive cardiac symphathetic activity.", "contents": "Effect of isometric exercise on catecholamines in the coronary circulation. Arterial and coronary sinus blood levels of catecholamines, adenosine 3', 5'-cyclic monophosphate (c-AMP) and lactate were measured during isometric exercise in fourteen patients. In no patient did lactate production occur. Mean resting total catecholamine levels both arterial (0.53 +/- 0.07 ng/ml; 2.94 +/- 0.38 nmol/l) and coronary sinus (0.4 +/- 0.08 ng/ml; 2.22 +/- 0.44 nmol/l), did not change significantly on exercise. Coronary sinus c-AMP levels fell on exercise from 11.5 +/- 0.8 nmol/l (resting) to 9.9 +/- 0.8 nmol/l (exercise) (P less than 0.01) with an arterial-coronary sinus difference of 1.2 nmol/l (P less than 0.01) on exercise. Our findings suggest that isometric exercise does not normally result in excessive cardiac symphathetic activity."}
{"id": "PMID:202453", "title": "The role of iron-sulfur center 2 in electron transport and energy conservation in the NADH-ubiquinone segment of the respiratory chain in Paracoccus denitrificans.", "content": "1. The electron paramagnetic resonance spectra at 15 K of reduced membrane particles of Paracoccus denitrificans exhibit resonance signals with g values, line shapes and temperature profile which are similar to the signals of the iron-sulfur centers observed in the NADH-ubiquinone segment of mitochondrial respiratory chains. These iron-sulfur centers are reducible with NADH, NADPH as well as chemically with dithionite. 2. Sulphate-limited growth of Paracoccus denitrificans results in the loss of an electron paramagnetic resonance signal (gz approximately 2.05, gy approximately gx approximately 1.92) which has properties similar to those of iron-sulfur center 2 of the NADH dehydrogenase of mitochondrial origin. The loss of this signal is accompanied by a decrease in the NADH oxidase and NADH ferricyanide oxidoreductase activities to respectively 30 and 40% of the values found for succinate-limited growth conditions. In addition respiration in membrane particles from sulphate-limited cells loses its sensitivity to rotenone. 3. Since sulphate-limited growth of Paracoccus denitrificans induces loss of site I phosphorylation [Arch. Microbiol. (1977) 112, 25-34] these observations suggest a close correlation between site I phosphorylation, rotenone-sensitivity and the presence of an electron paramagnetic resonance signal with gz approximately 2.05 and gy approximately gx approximately 1.92.", "contents": "The role of iron-sulfur center 2 in electron transport and energy conservation in the NADH-ubiquinone segment of the respiratory chain in Paracoccus denitrificans. 1. The electron paramagnetic resonance spectra at 15 K of reduced membrane particles of Paracoccus denitrificans exhibit resonance signals with g values, line shapes and temperature profile which are similar to the signals of the iron-sulfur centers observed in the NADH-ubiquinone segment of mitochondrial respiratory chains. These iron-sulfur centers are reducible with NADH, NADPH as well as chemically with dithionite. 2. Sulphate-limited growth of Paracoccus denitrificans results in the loss of an electron paramagnetic resonance signal (gz approximately 2.05, gy approximately gx approximately 1.92) which has properties similar to those of iron-sulfur center 2 of the NADH dehydrogenase of mitochondrial origin. The loss of this signal is accompanied by a decrease in the NADH oxidase and NADH ferricyanide oxidoreductase activities to respectively 30 and 40% of the values found for succinate-limited growth conditions. In addition respiration in membrane particles from sulphate-limited cells loses its sensitivity to rotenone. 3. Since sulphate-limited growth of Paracoccus denitrificans induces loss of site I phosphorylation [Arch. Microbiol. (1977) 112, 25-34] these observations suggest a close correlation between site I phosphorylation, rotenone-sensitivity and the presence of an electron paramagnetic resonance signal with gz approximately 2.05 and gy approximately gx approximately 1.92."}
{"id": "PMID:202454", "title": "Changes in enzyme activities during the artificially stimulated transition from follicular to luteal cell types in rat ovary.", "content": "This paper reports the time course of development of the intramitochondrial cholesterol side-chain-cleavage activity, cytoplasmic NADP+-dependent isocitric dehydrogenase, malic enzyme and glucose-6-phosphate dehydrogenase during ovarian maturation, using as a model the immature rat ovary stimulated to develop with pharmacological doses of gonadotrophin. These enzymic activities were correlated with increases in ovarian content of DNA, cellular content of adenosin 3':5'-monophosphate, and the levels of plasma progesterone. The plasma progesterone concentrations followed closely the development of the [4-14C]cholesterol side-chain-cleavage which was mimicked by the cytoplasmic isocitric dehydrogenase; both enzymes increased in activity 28 times during the 6 days of this study. There was no correlation between adenosine 3':5'-monophosphate levels and cholesterol side-chain cleavage or progesterone plasma concentrations.", "contents": "Changes in enzyme activities during the artificially stimulated transition from follicular to luteal cell types in rat ovary. This paper reports the time course of development of the intramitochondrial cholesterol side-chain-cleavage activity, cytoplasmic NADP+-dependent isocitric dehydrogenase, malic enzyme and glucose-6-phosphate dehydrogenase during ovarian maturation, using as a model the immature rat ovary stimulated to develop with pharmacological doses of gonadotrophin. These enzymic activities were correlated with increases in ovarian content of DNA, cellular content of adenosin 3':5'-monophosphate, and the levels of plasma progesterone. The plasma progesterone concentrations followed closely the development of the [4-14C]cholesterol side-chain-cleavage which was mimicked by the cytoplasmic isocitric dehydrogenase; both enzymes increased in activity 28 times during the 6 days of this study. There was no correlation between adenosine 3':5'-monophosphate levels and cholesterol side-chain cleavage or progesterone plasma concentrations."}
{"id": "PMID:202455", "title": "Metal-free and metal-substituted cytochromes c. Use in characterization of the cytochrome c binding site.", "content": "The luminescent properties of metal-free, tin(IV) and zinc(II) cytochromes c have been used to characterize the interaction of cytochrome c with mitochondria and cytochrome oxidase. Diminution in the fluorescence yields of tin and zinc cytochrome c occur when these derivates bind to cytochrome oxidase or mitochondria. Based upon spectral overlap and quantum yield, the distance between the porphyrin rings of cytochrome a and cytochrome c is estimated according to Forster theory to be in the neighborhood of 3.5 nm. Measurements of the polarized emission of metal-free 'porphyrin' cytochrome c when bound to oriented layers of cytochrome c oxidase indicate that the porphyrin is bound obliquely to the plane of the oxidase layers with an angle of about 70 degrees C from heme plane to membrane plane. It is proposed that these data have significance for elucidation of electron transfer mechanisms.", "contents": "Metal-free and metal-substituted cytochromes c. Use in characterization of the cytochrome c binding site. The luminescent properties of metal-free, tin(IV) and zinc(II) cytochromes c have been used to characterize the interaction of cytochrome c with mitochondria and cytochrome oxidase. Diminution in the fluorescence yields of tin and zinc cytochrome c occur when these derivates bind to cytochrome oxidase or mitochondria. Based upon spectral overlap and quantum yield, the distance between the porphyrin rings of cytochrome a and cytochrome c is estimated according to Forster theory to be in the neighborhood of 3.5 nm. Measurements of the polarized emission of metal-free 'porphyrin' cytochrome c when bound to oriented layers of cytochrome c oxidase indicate that the porphyrin is bound obliquely to the plane of the oxidase layers with an angle of about 70 degrees C from heme plane to membrane plane. It is proposed that these data have significance for elucidation of electron transfer mechanisms."}
{"id": "PMID:202456", "title": "Intermediates in the conversion of procollagen to collagen. Evidence for stepwise limited proteolysis of the COOH-terminal peptide extensions.", "content": "Intermediates in the conversion of procollagen to collagen were isolated from radioactively labeled chick cranial bones by ion-exchange chromatography. Cleavage of these proteins with vertebrate collagenase revealed that each of the several forms of these intermediates lacked NH2-terminal but retained COOH-terminal extensions. The chain composition of each intermediate was resolved by two-dimensional slab gel electrophoresis. The intermediates differed from each other in having sustained cleavages in zero, one or two pcalpha chains. The relative proportions of intermediates with different intact pcalpha chains, observed in conversion of procollagen, have enabled us to construct a detailed model of the stepwise limited proteolysis of procollagen.", "contents": "Intermediates in the conversion of procollagen to collagen. Evidence for stepwise limited proteolysis of the COOH-terminal peptide extensions. Intermediates in the conversion of procollagen to collagen were isolated from radioactively labeled chick cranial bones by ion-exchange chromatography. Cleavage of these proteins with vertebrate collagenase revealed that each of the several forms of these intermediates lacked NH2-terminal but retained COOH-terminal extensions. The chain composition of each intermediate was resolved by two-dimensional slab gel electrophoresis. The intermediates differed from each other in having sustained cleavages in zero, one or two pcalpha chains. The relative proportions of intermediates with different intact pcalpha chains, observed in conversion of procollagen, have enabled us to construct a detailed model of the stepwise limited proteolysis of procollagen."}
{"id": "PMID:202458", "title": "Fate of histone messenger RNA in mengovirus-infected Ehrlich ascites tumor cells.", "content": "Histone mRNA was isolated from mengovirus-infected Ehrlich ascites tumor cells at various times postinfection and quantitated in a reticulocyte cell-free protein-synthesizing system. The amount of translatable histone mRNA decreases during the first hour postinfection by 30%, rises during the following 1-1.5 h by 10-15%, drops progressively in the further course of infection, and reaches 20% of the control at the end of the infectious cycle (8-9 h postinfection). On the basis of the relative histone mRNA contents, the histone-synthesizing potentials of mengovirus-infected Ehrlich ascites tumor cells are substantially higher throughout infection than actually expressed in vivo. This result indicates that the virus-induced shutoff of histone synthesis is not directly the consequence of inactivation or degradation of histone mRNA. Most of the histone mRNA recovered from mengovirus-infected Ehrlich ascites tumor cells is bound to ribosomes. Late in infection, certain mRNAs are co-isolated with histone mRNAs, very likely due to loss or shortening of poly(A) occurring after release of the mRNAs from polyribosomes.", "contents": "Fate of histone messenger RNA in mengovirus-infected Ehrlich ascites tumor cells. Histone mRNA was isolated from mengovirus-infected Ehrlich ascites tumor cells at various times postinfection and quantitated in a reticulocyte cell-free protein-synthesizing system. The amount of translatable histone mRNA decreases during the first hour postinfection by 30%, rises during the following 1-1.5 h by 10-15%, drops progressively in the further course of infection, and reaches 20% of the control at the end of the infectious cycle (8-9 h postinfection). On the basis of the relative histone mRNA contents, the histone-synthesizing potentials of mengovirus-infected Ehrlich ascites tumor cells are substantially higher throughout infection than actually expressed in vivo. This result indicates that the virus-induced shutoff of histone synthesis is not directly the consequence of inactivation or degradation of histone mRNA. Most of the histone mRNA recovered from mengovirus-infected Ehrlich ascites tumor cells is bound to ribosomes. Late in infection, certain mRNAs are co-isolated with histone mRNAs, very likely due to loss or shortening of poly(A) occurring after release of the mRNAs from polyribosomes."}
{"id": "PMID:202459", "title": "The crystal structure of complexes between horse liver alcohol dehydrogenase and the coenzyme analogues 3-iodopyridine-adenine dinucleotide and pyridine-adenine dinucleotide.", "content": "We have studied the binding of the enzymatically active NAD+ analogue, 3-iodopyridine-adenine dinucleotide, and the inactive analogue, pyridine-adenine dinucleotide to the enzyme horse liver alcohol dehydrogenase using X-ray crystallographic methods. These studies were made under such conditions that crystals of the complexes were isomorphous to apoenzyme crystals. Both analogues bind in the same conformation. The binding of the adenosine moiety is very similar to that of ADP-ribose or NADH bound to the enzyme. The conformation and mode of binding of the remaining portions of the analogue molecules is, however, quite different. The pyridine ring is not situated in the active-site pocket as the nicotinamide group in the isomorphous enzyme-NADH-imidazole complex but lies at the surface of the crevice between the two domains of the subunit, approximately 1.5 nm away from the catalytically active zinc atom. Lys-228 which has been shown to be important for NADH dissociation is in this region of the molecule.", "contents": "The crystal structure of complexes between horse liver alcohol dehydrogenase and the coenzyme analogues 3-iodopyridine-adenine dinucleotide and pyridine-adenine dinucleotide. We have studied the binding of the enzymatically active NAD+ analogue, 3-iodopyridine-adenine dinucleotide, and the inactive analogue, pyridine-adenine dinucleotide to the enzyme horse liver alcohol dehydrogenase using X-ray crystallographic methods. These studies were made under such conditions that crystals of the complexes were isomorphous to apoenzyme crystals. Both analogues bind in the same conformation. The binding of the adenosine moiety is very similar to that of ADP-ribose or NADH bound to the enzyme. The conformation and mode of binding of the remaining portions of the analogue molecules is, however, quite different. The pyridine ring is not situated in the active-site pocket as the nicotinamide group in the isomorphous enzyme-NADH-imidazole complex but lies at the surface of the crevice between the two domains of the subunit, approximately 1.5 nm away from the catalytically active zinc atom. Lys-228 which has been shown to be important for NADH dissociation is in this region of the molecule."}
{"id": "PMID:202461", "title": "Kinetic studies on the transport of cytoplasmically synthesized proteins into the mitochondria in intact cells of Neurospora crassa.", "content": "The transport of cytoplasmically synthesized mitochondrial proteins was investigated in whole cells of Neurospora crassa, using dual labelling and immunological techniques. In pulse and pulse-chase labelling experiments the mitochondrial proteins accumulate label. The appearance of label in mitochondrial protein shows a lag relative to total cellular protein, ribosomal, microsomal and cytosolic proteins. The delayed appearance of label was also found in immunoprecipitated mitochondrial matrix proteins, mitochondrial ribosomal proteins, mitochondrial carboxyatractyloside-binding protein and cytochrome c. Individual mitochondrial proteins exhibit different labelling kinetics. Cycloheximide inhibition of translation does not prevent import of proteins into the mitochondria. Mitochondrial matrix proteins labelled in pulse and pulse-chase experiments can first be detected in the cytosol fraction and subsequently in the mitochondria. The cytosol matrix proteins and those in the mitochondria show a precursor-product type relationship. The results suggest that newly synthesized mitochondrial proteins exist in an extra-mitochondrial pool from which they are imported into the mitochondria.", "contents": "Kinetic studies on the transport of cytoplasmically synthesized proteins into the mitochondria in intact cells of Neurospora crassa. The transport of cytoplasmically synthesized mitochondrial proteins was investigated in whole cells of Neurospora crassa, using dual labelling and immunological techniques. In pulse and pulse-chase labelling experiments the mitochondrial proteins accumulate label. The appearance of label in mitochondrial protein shows a lag relative to total cellular protein, ribosomal, microsomal and cytosolic proteins. The delayed appearance of label was also found in immunoprecipitated mitochondrial matrix proteins, mitochondrial ribosomal proteins, mitochondrial carboxyatractyloside-binding protein and cytochrome c. Individual mitochondrial proteins exhibit different labelling kinetics. Cycloheximide inhibition of translation does not prevent import of proteins into the mitochondria. Mitochondrial matrix proteins labelled in pulse and pulse-chase experiments can first be detected in the cytosol fraction and subsequently in the mitochondria. The cytosol matrix proteins and those in the mitochondria show a precursor-product type relationship. The results suggest that newly synthesized mitochondrial proteins exist in an extra-mitochondrial pool from which they are imported into the mitochondria."}
{"id": "PMID:202462", "title": "Quantitative determination of myoinositol, inositol 1-phosphate, inositol cyclic 1 : 2-phosphate and glycerylphosphoinositol in normal and Rous-sarcoma-virus-transformed quail fibroblasts under different growth conditions.", "content": "Myoinositol and its phosphorylated derivatives have been quantitatively determined in normal and Rous-sarcoma-virus-transformed quail cells under various growth conditions using [2-(3)H]myoinositol at isotope equilibrium conditions. The following amounts were determined (nmol/mumol phospholipid, as a unit of cell mass): exponentially growing normal and tumor cells contained 25--40 nmol free inositol, 0.40--0.45 nmol myoinositol 1-phosphate, 0.30--0.50 nmol glycerylphosphoinositol, and 0.03--0.04 nmol myoinositol cyclic 1 : 2-phosphate. At high cell populations in the absence of serum, conditions which result in cessation of growth by normal but not by tumor cells, changed levels were found for glycerylphosphoinositol and free inositol. In tumor cells the levels of these two compounds increased to 0.64 nmol and 64 nmol, respectively. In normal cells glycerylphosphoinositol increased to 0.95 nmol and free inositol showed highly elevated levels of 144 nmol. At short pulses the specific activities of inositol 1-phosphate and inositol cyclic 1 : 2-phosphate were found to be higher than that of phosphatidylinositol. This was not the case for glycerylphosphoinositol.", "contents": "Quantitative determination of myoinositol, inositol 1-phosphate, inositol cyclic 1 : 2-phosphate and glycerylphosphoinositol in normal and Rous-sarcoma-virus-transformed quail fibroblasts under different growth conditions. Myoinositol and its phosphorylated derivatives have been quantitatively determined in normal and Rous-sarcoma-virus-transformed quail cells under various growth conditions using [2-(3)H]myoinositol at isotope equilibrium conditions. The following amounts were determined (nmol/mumol phospholipid, as a unit of cell mass): exponentially growing normal and tumor cells contained 25--40 nmol free inositol, 0.40--0.45 nmol myoinositol 1-phosphate, 0.30--0.50 nmol glycerylphosphoinositol, and 0.03--0.04 nmol myoinositol cyclic 1 : 2-phosphate. At high cell populations in the absence of serum, conditions which result in cessation of growth by normal but not by tumor cells, changed levels were found for glycerylphosphoinositol and free inositol. In tumor cells the levels of these two compounds increased to 0.64 nmol and 64 nmol, respectively. In normal cells glycerylphosphoinositol increased to 0.95 nmol and free inositol showed highly elevated levels of 144 nmol. At short pulses the specific activities of inositol 1-phosphate and inositol cyclic 1 : 2-phosphate were found to be higher than that of phosphatidylinositol. This was not the case for glycerylphosphoinositol."}
{"id": "PMID:202465", "title": "The binding of calcium and magnesium to sarcoplasmic reticulum vesicles as studied by manganese electron paramagnetic resonance.", "content": "The binding pattern of the biologically relevant ions calcium and magnesium has been investigated via the binding  of the ion-analogue manganese. The binding parameters of manganese are obtained conveniently by standard electron paramagnetic resonance techniques, the binding of calcium and magnesium is inferred from competition experiments. The quantitative analysis was carried out with a computer program which was able to treat the competition of three kinds of ions for three classes of independent and one class of cooperative binding sites. It was possible to correlate specific binding classes with biological functions of the sarcoplasmic reticulum membrane. The magnesium and manganese specific binding class of medium affinity is related to the catalytic function of these ions in the ATP-splitting. For the first time a manganese and calcium specific class of cooperative binding sites has been observed and it can be related to the inhibition of the calcium transport at high concentrations of manganese or calcium. From the binding results a model can be developed which allows a full description of the role of the divalent ions and their specific binding sites during calcium transport.", "contents": "The binding of calcium and magnesium to sarcoplasmic reticulum vesicles as studied by manganese electron paramagnetic resonance. The binding pattern of the biologically relevant ions calcium and magnesium has been investigated via the binding  of the ion-analogue manganese. The binding parameters of manganese are obtained conveniently by standard electron paramagnetic resonance techniques, the binding of calcium and magnesium is inferred from competition experiments. The quantitative analysis was carried out with a computer program which was able to treat the competition of three kinds of ions for three classes of independent and one class of cooperative binding sites. It was possible to correlate specific binding classes with biological functions of the sarcoplasmic reticulum membrane. The magnesium and manganese specific binding class of medium affinity is related to the catalytic function of these ions in the ATP-splitting. For the first time a manganese and calcium specific class of cooperative binding sites has been observed and it can be related to the inhibition of the calcium transport at high concentrations of manganese or calcium. From the binding results a model can be developed which allows a full description of the role of the divalent ions and their specific binding sites during calcium transport."}
{"id": "PMID:202466", "title": "The structure of human-plasma low-density lipoprotein B. An X-ray small-angle scattering study.", "content": "1. X-ray small-angle scattering of human plasma lipoprotein B of the low-density fraction (rho = 1.016--1.060 g.cm-3) has been recorded to high precision at different electron density contrasts. 2. The overall structure of the particles is characterized by a quasi-spherical shape and radial symmetry. A maximum diameter of 23 nm and a molecular weight of 2.4 X 10(6) have been determined. 3. The internal structure is described in terms of a model consisting of spherical layers with different electron densities indicating that the neutral lipids are arranged in the core of the molecule up to a radius of about 8 nm surrounded by a monolayer of free cholesterol, phospholipids and protein. The neural lipids are shown to be in an ordered, liquid crystalline state at 4 degrees C and to undergo a thermotropic transition into a disordered state at higher temperatures.", "contents": "The structure of human-plasma low-density lipoprotein B. An X-ray small-angle scattering study. 1. X-ray small-angle scattering of human plasma lipoprotein B of the low-density fraction (rho = 1.016--1.060 g.cm-3) has been recorded to high precision at different electron density contrasts. 2. The overall structure of the particles is characterized by a quasi-spherical shape and radial symmetry. A maximum diameter of 23 nm and a molecular weight of 2.4 X 10(6) have been determined. 3. The internal structure is described in terms of a model consisting of spherical layers with different electron densities indicating that the neutral lipids are arranged in the core of the molecule up to a radius of about 8 nm surrounded by a monolayer of free cholesterol, phospholipids and protein. The neural lipids are shown to be in an ordered, liquid crystalline state at 4 degrees C and to undergo a thermotropic transition into a disordered state at higher temperatures."}
{"id": "PMID:202467", "title": "Effect of methylxanthines on binding of the glucocorticoid receptor to DNA-cellulose and nuclei.", "content": "The binding of [3H]dexamethasone-receptor complex from rat liver cytosol to isolated nuclei or DNA-cellulose can be greatly enhanced at low temperature by the presence of theophylline. Aminophylline and caffeine can mimic this effect; however, papaverine and 1-methyl-3-isobutylxanthine, at concentrations inhibitory to phosphodiesterase, are without effect on glucocorticoid receptor binding to DNA. Furthermore, theophylline can be added when adenosine 3':5'-monophosphate-(cAMP) hydrolysis is already complete and still enhance DNA binding. These results imply that this effect of theophylline is independent of its known effect on cAMP levels. Activation by methylxanthines does not alter the sedimentation of the glucocorticoid-receptor complex in sucrose gradients but does alter the pI and in this respect brings about changes resembling those which occur upon activation by heat. Recently we have shown that pyridoxal phosphate inhibits the binding of heat-activated receptor to DNA-cellulose. Similarly, we have shown here that pyridoxal phosphate also inhibits the DNA-cellulose binding of theophylline-treated receptor. The presence of theophylline also enhances the rate of binding of [3H]dexamethasone to the receptor and increases its apparent affininty for the steroid. The data suggest that the effect of theophylline is on some cytosolic component, perhaps the receptor itself. Enhanced DNA binding as a result of exposure to theophylline at low temperature can also be demonstrated using the glucocorticoid receptor of kidney, thymus and Reuber H35 cells.", "contents": "Effect of methylxanthines on binding of the glucocorticoid receptor to DNA-cellulose and nuclei. The binding of [3H]dexamethasone-receptor complex from rat liver cytosol to isolated nuclei or DNA-cellulose can be greatly enhanced at low temperature by the presence of theophylline. Aminophylline and caffeine can mimic this effect; however, papaverine and 1-methyl-3-isobutylxanthine, at concentrations inhibitory to phosphodiesterase, are without effect on glucocorticoid receptor binding to DNA. Furthermore, theophylline can be added when adenosine 3':5'-monophosphate-(cAMP) hydrolysis is already complete and still enhance DNA binding. These results imply that this effect of theophylline is independent of its known effect on cAMP levels. Activation by methylxanthines does not alter the sedimentation of the glucocorticoid-receptor complex in sucrose gradients but does alter the pI and in this respect brings about changes resembling those which occur upon activation by heat. Recently we have shown that pyridoxal phosphate inhibits the binding of heat-activated receptor to DNA-cellulose. Similarly, we have shown here that pyridoxal phosphate also inhibits the DNA-cellulose binding of theophylline-treated receptor. The presence of theophylline also enhances the rate of binding of [3H]dexamethasone to the receptor and increases its apparent affininty for the steroid. The data suggest that the effect of theophylline is on some cytosolic component, perhaps the receptor itself. Enhanced DNA binding as a result of exposure to theophylline at low temperature can also be demonstrated using the glucocorticoid receptor of kidney, thymus and Reuber H35 cells."}
{"id": "PMID:202471", "title": "Two mechanisms of isoproterenol inhibition of smooth muscle.", "content": "The relaxation of depolarized ideal and uterine smooth muscle by isoproterenol was compared with that brought about by dibutyryl-cAMP and by other agents which increase cytoplasmic cAMP. Qualitative differences observed between the time courses of the relaxations imply the existence of a rapid beta-adrenergic mechanism independent of cAMP as well as a slower cAMP-dependent relaxation. This dual process model for beta-adrenergic inhibition of smooth muscle is consistent with seemingly opposing published reports.", "contents": "Two mechanisms of isoproterenol inhibition of smooth muscle. The relaxation of depolarized ideal and uterine smooth muscle by isoproterenol was compared with that brought about by dibutyryl-cAMP and by other agents which increase cytoplasmic cAMP. Qualitative differences observed between the time courses of the relaxations imply the existence of a rapid beta-adrenergic mechanism independent of cAMP as well as a slower cAMP-dependent relaxation. This dual process model for beta-adrenergic inhibition of smooth muscle is consistent with seemingly opposing published reports."}
{"id": "PMID:202474", "title": "Spinal branching of rubrospinal axons in the cat.", "content": "The branching patterns of rubrospinal (RS) axons projecting to the cervical spinal cord between C3 and C8 were studied in the cat. RS neurons were identified by their antidromic responses to microstimulation of local axon branches within the cervical gray matter. Twenty-six of 58 RS neurons projecting to the cervical gray matter also sent axon branches to the thoracic spinal cord. Two out of 40 of these RS neurons also sent axon branches to the lumbar spinal cord. Using a collision technique, it was demonstrated that stem axons of rubrospinal neurons commonly sent multiple collaterals to different cervical segments. Neurons projecting to the cervical spinal cord alone were located in the dorsal quadrants of the red nucleus. Those projecting to cervical, as well as to more caudal segments, were intermingled with the former, and in slightly more ventral portions of the red nucleus. The presence of RS neurons projecting to widely separate levels of the spinal cord suggests that individual RS neurons may be capable of ultimately influencing two or more different motoneuron pools.", "contents": "Spinal branching of rubrospinal axons in the cat. The branching patterns of rubrospinal (RS) axons projecting to the cervical spinal cord between C3 and C8 were studied in the cat. RS neurons were identified by their antidromic responses to microstimulation of local axon branches within the cervical gray matter. Twenty-six of 58 RS neurons projecting to the cervical gray matter also sent axon branches to the thoracic spinal cord. Two out of 40 of these RS neurons also sent axon branches to the lumbar spinal cord. Using a collision technique, it was demonstrated that stem axons of rubrospinal neurons commonly sent multiple collaterals to different cervical segments. Neurons projecting to the cervical spinal cord alone were located in the dorsal quadrants of the red nucleus. Those projecting to cervical, as well as to more caudal segments, were intermingled with the former, and in slightly more ventral portions of the red nucleus. The presence of RS neurons projecting to widely separate levels of the spinal cord suggests that individual RS neurons may be capable of ultimately influencing two or more different motoneuron pools."}
{"id": "PMID:202475", "title": "Properties of the synaptic transmission of the newly formed cortico-rubral synapses after lesion of the nucleus interpositus of the cerebellum.", "content": "1. Properties of synaptic transmission during and after repetitive activation of the newly formed cortico-rubral were examined in the red nucleus neurons (RN) of cats after lesions of the nucleus interpositus of the cerebellum (chronic cats) as well as in normal ones. 2. A prominent facilitation of the amplitude of cortico-rubral unitary EPSPs was observed in both normal and chronic cats when a stimulus to the cerebral peduncle (CP) was preceded by another stimulus by 2-50 msec. 3. Time course of the facilitation shows that it attains maximum at the interval of about 3 msec and decays approximately exponentially lasting for 50 msec or more. 4. When three successive stimuli of identical intensity were applied to CP, the degree of facilitation was more prominent than that for double shock. 5. There was a positive correlation between the time to peak of the cortico-rubral EPSPs and their maximum value of facilitation. 6. The posttetanic potentiation of the cortico-rubral EPSPs was observed after tetanic stimulation to CP in chronic and normal cats. It lasts for a few minutes in both cases.", "contents": "Properties of the synaptic transmission of the newly formed cortico-rubral synapses after lesion of the nucleus interpositus of the cerebellum. 1. Properties of synaptic transmission during and after repetitive activation of the newly formed cortico-rubral were examined in the red nucleus neurons (RN) of cats after lesions of the nucleus interpositus of the cerebellum (chronic cats) as well as in normal ones. 2. A prominent facilitation of the amplitude of cortico-rubral unitary EPSPs was observed in both normal and chronic cats when a stimulus to the cerebral peduncle (CP) was preceded by another stimulus by 2-50 msec. 3. Time course of the facilitation shows that it attains maximum at the interval of about 3 msec and decays approximately exponentially lasting for 50 msec or more. 4. When three successive stimuli of identical intensity were applied to CP, the degree of facilitation was more prominent than that for double shock. 5. There was a positive correlation between the time to peak of the cortico-rubral EPSPs and their maximum value of facilitation. 6. The posttetanic potentiation of the cortico-rubral EPSPs was observed after tetanic stimulation to CP in chronic and normal cats. It lasts for a few minutes in both cases."}
{"id": "PMID:202476", "title": "Ultrastructural responses of the hypoglossal nucleus to the presence in the tongue of botulinum toxin, a quantitative study.", "content": "The ultrastructural effects of local injection of botulinum toxin into the left half of the tongue of the rat, were studied quantitatively 35 days postoperatively in the left hypoglossal nucleus. The results showed (1) a decrease in somatic and neuropil bouton numbers because of loss of boutons with symmetrical synapses and clear spherical synaptic vesicles, (2) a decrease in the numbers of dendrite profiles in the neuropil, (3) an increase in the proportion of dendrites and boutons with unusual inclusions, suggestive of profile retraction, (4) an increase in the proportion of profiles which were unusually electron-dense, (5) an increase in the amount of astrocyte, and a growth of astrocyte sheaths around bouton-free neurone surfaces, (6) the presence of occasional microglia, and (7) subastrocytic subsurface cisterns. Control rats injected with boiled toxin had no responses except (3) and (4) above, and then only to a modest extent, possibly due to mechanical damage of a few axons or terminals at the time of injection, or to insufficient inactivation of the toxin by boiling. The results were compared with those at 35 days after axotomy, and it was concluded that botulinum toxin, which interrupts neuromuscular transmission, elicits the same responses in the hypoglossal neurones, as does transection of the hypoglossal nerve, even though earlier studies had discovered no glial replication after botulinum toxin, in contrast to axotomy.", "contents": "Ultrastructural responses of the hypoglossal nucleus to the presence in the tongue of botulinum toxin, a quantitative study. The ultrastructural effects of local injection of botulinum toxin into the left half of the tongue of the rat, were studied quantitatively 35 days postoperatively in the left hypoglossal nucleus. The results showed (1) a decrease in somatic and neuropil bouton numbers because of loss of boutons with symmetrical synapses and clear spherical synaptic vesicles, (2) a decrease in the numbers of dendrite profiles in the neuropil, (3) an increase in the proportion of dendrites and boutons with unusual inclusions, suggestive of profile retraction, (4) an increase in the proportion of profiles which were unusually electron-dense, (5) an increase in the amount of astrocyte, and a growth of astrocyte sheaths around bouton-free neurone surfaces, (6) the presence of occasional microglia, and (7) subastrocytic subsurface cisterns. Control rats injected with boiled toxin had no responses except (3) and (4) above, and then only to a modest extent, possibly due to mechanical damage of a few axons or terminals at the time of injection, or to insufficient inactivation of the toxin by boiling. The results were compared with those at 35 days after axotomy, and it was concluded that botulinum toxin, which interrupts neuromuscular transmission, elicits the same responses in the hypoglossal neurones, as does transection of the hypoglossal nerve, even though earlier studies had discovered no glial replication after botulinum toxin, in contrast to axotomy."}
{"id": "PMID:202478", "title": "Study of histochemical and biochemical changes in the liver of rats induced by high doses of isoprenaline.", "content": "The aim of the present work was to study by means of histochemical and chemical methods the 7-day course of changes in carbohydrate metabolism in the liver of male rats induced by a single dose of isoprenaline of 50 mg/kg administered subcutaneously. A statistically significant reduction was seen both in the level of free glycogen and lactate within 24 hours. The decrease of pyruvate level was not so marked. At the same time, there was increased, and within the hepatic lobules also extended activity of enzymes catalyzing glycogenolysis, i.e. alpha-glucan phosphorylase and particularly the branching Q-enzyme, glucose-6-phosphatase and LDH, whereas the level of malate and activity of SDH, which are constituents of the Krebs cycle, were found to be reduced. Cytochrome oxidase activity was changed after 24 hr compared to the controls. The obtained results indicate that an extensive glycogenolysis occurs in the liver of rats in the 24 hr following s.c. administration of isoprenaline, the major part of liver glycogen being degraded through glucose-6-phosphate to blood glucose and its metabolism via the Krebs cycle reduced. The observed metabolic changes are of reversible character and tend to normalize over the 2nd and 3rd day following isoprenaline administration.", "contents": "Study of histochemical and biochemical changes in the liver of rats induced by high doses of isoprenaline. The aim of the present work was to study by means of histochemical and chemical methods the 7-day course of changes in carbohydrate metabolism in the liver of male rats induced by a single dose of isoprenaline of 50 mg/kg administered subcutaneously. A statistically significant reduction was seen both in the level of free glycogen and lactate within 24 hours. The decrease of pyruvate level was not so marked. At the same time, there was increased, and within the hepatic lobules also extended activity of enzymes catalyzing glycogenolysis, i.e. alpha-glucan phosphorylase and particularly the branching Q-enzyme, glucose-6-phosphatase and LDH, whereas the level of malate and activity of SDH, which are constituents of the Krebs cycle, were found to be reduced. Cytochrome oxidase activity was changed after 24 hr compared to the controls. The obtained results indicate that an extensive glycogenolysis occurs in the liver of rats in the 24 hr following s.c. administration of isoprenaline, the major part of liver glycogen being degraded through glucose-6-phosphate to blood glucose and its metabolism via the Krebs cycle reduced. The observed metabolic changes are of reversible character and tend to normalize over the 2nd and 3rd day following isoprenaline administration."}
{"id": "PMID:202479", "title": "Serum activity inhibiting specific simian virus 40-induced transplantation resistance and its correlation with primary SV40 tumors appearance in hamsters.", "content": "Using the modified technique of transplantation test, ITR serum activity was found in most (14 out of 21) individual hamster sera obtained during the latent period of primary SV40 carcinogenesis (60 days after virus infection when newborn). On the other hand, as a rule, no ITR activity was observed in the sera of the same hamsters after tumor appearance and during their growth. ITR activity rapidly disappeared from sera of hamsters neonatally infected with SV40 after their successful immunization with the same virus during the latent period. There appears to be a correlation between the presence of ITR serum factor during the latent period and the subsequent primary SV40 tumor appearance in hamsters.", "contents": "Serum activity inhibiting specific simian virus 40-induced transplantation resistance and its correlation with primary SV40 tumors appearance in hamsters. Using the modified technique of transplantation test, ITR serum activity was found in most (14 out of 21) individual hamster sera obtained during the latent period of primary SV40 carcinogenesis (60 days after virus infection when newborn). On the other hand, as a rule, no ITR activity was observed in the sera of the same hamsters after tumor appearance and during their growth. ITR activity rapidly disappeared from sera of hamsters neonatally infected with SV40 after their successful immunization with the same virus during the latent period. There appears to be a correlation between the presence of ITR serum factor during the latent period and the subsequent primary SV40 tumor appearance in hamsters."}
{"id": "PMID:202480", "title": "Investigations into the effects of ACTH on the half-life of mitochondrial proteins in the rat adrenal cortex.", "content": "ACTH elongates the half-life of the mitochondrial proteins from the rat adrenal cortex, and chloramphenicol inhibits this effect of ACTH. The hypothesis is advanced that the ACTH-provoked stabilization of the adrenocortical mitochondrial proteins requires continuous mitochondrial DNA-dependent protein synthesis.", "contents": "Investigations into the effects of ACTH on the half-life of mitochondrial proteins in the rat adrenal cortex. ACTH elongates the half-life of the mitochondrial proteins from the rat adrenal cortex, and chloramphenicol inhibits this effect of ACTH. The hypothesis is advanced that the ACTH-provoked stabilization of the adrenocortical mitochondrial proteins requires continuous mitochondrial DNA-dependent protein synthesis."}
{"id": "PMID:202481", "title": "Modulation of transmission in different electronic junctions by aminopyridine.", "content": "4 distinct electronic inputs can be identified in amphibian motoneurons perfused with calcium-free solution containing manganese. The differential effect of 4-aminopyridine on different electronic junctions may reflect the peculiarities of molecular architecture of potassium channels in different electrically excitable presynaptic membranes.", "contents": "Modulation of transmission in different electronic junctions by aminopyridine. 4 distinct electronic inputs can be identified in amphibian motoneurons perfused with calcium-free solution containing manganese. The differential effect of 4-aminopyridine on different electronic junctions may reflect the peculiarities of molecular architecture of potassium channels in different electrically excitable presynaptic membranes."}
{"id": "PMID:202482", "title": "GABAergic inhibition of neurons in the ventral tegmental area.", "content": "Stimulation of the nucleus accumbens evokes a potent inhibition in neurons of the ventral tegmental area. GABA is likely to act as a transmitter in this descending inhibitory system.", "contents": "GABAergic inhibition of neurons in the ventral tegmental area. Stimulation of the nucleus accumbens evokes a potent inhibition in neurons of the ventral tegmental area. GABA is likely to act as a transmitter in this descending inhibitory system."}
{"id": "PMID:202511", "title": "[Temporal characteristics of sleep in the dog].", "content": "Main time characteristics of sleep were studied in 9 adult dogs in experiments with 24-hr polygraphic recordings. The all-day sleep quantity (35%), circadian distribution of sleep with the maximum between 24 and 9 hours, more rapid rise of delta-sleep (DS) in the second half of day and of REM sleep in the first hours of night -- all these data suggest that the dog sleep schedule is under considerable influence of ecological factors related to time organization of activity and sleep in humans. A relatively high amount of drowsiness in dog's sleep (nearly 25%) is comparable with DS representation. REM occupies about 20% of total sleep time. Mean REM cycle lasts 30 min. The data obtained can be used as the standards of dog sleep in neurophysiological, pharmacological and behavioral studies.", "contents": "[Temporal characteristics of sleep in the dog]. Main time characteristics of sleep were studied in 9 adult dogs in experiments with 24-hr polygraphic recordings. The all-day sleep quantity (35%), circadian distribution of sleep with the maximum between 24 and 9 hours, more rapid rise of delta-sleep (DS) in the second half of day and of REM sleep in the first hours of night -- all these data suggest that the dog sleep schedule is under considerable influence of ecological factors related to time organization of activity and sleep in humans. A relatively high amount of drowsiness in dog's sleep (nearly 25%) is comparable with DS representation. REM occupies about 20% of total sleep time. Mean REM cycle lasts 30 min. The data obtained can be used as the standards of dog sleep in neurophysiological, pharmacological and behavioral studies."}
{"id": "PMID:202512", "title": "[Local temperature characteristics of the isolated cortex in wakefulness and alteration of the sleep stages].", "content": "In cats, changes of the brain electric activity were followed by local temperature shifts in isolated and in intact cortex: the transition from slow wave sleep to paradoxical sleep and from quiet to active wakefulness were accompanied by increasing of the cortex temperature, while transition from paradoxical sleep to slow sleep decreased the temperature. During falling asleep and alternation of the sleep stages, both in isolated and intact cortex, the temperature shifts preceded the electric activity changes. The temperature of isolated cortex is by 0.2 degrees lower than that of the opposite intact hemisphere.", "contents": "[Local temperature characteristics of the isolated cortex in wakefulness and alteration of the sleep stages]. In cats, changes of the brain electric activity were followed by local temperature shifts in isolated and in intact cortex: the transition from slow wave sleep to paradoxical sleep and from quiet to active wakefulness were accompanied by increasing of the cortex temperature, while transition from paradoxical sleep to slow sleep decreased the temperature. During falling asleep and alternation of the sleep stages, both in isolated and intact cortex, the temperature shifts preceded the electric activity changes. The temperature of isolated cortex is by 0.2 degrees lower than that of the opposite intact hemisphere."}
{"id": "PMID:202513", "title": "[Effect of anticholinesterase agents on the protein and RNA content in the cells of the supraoptic nucleus during sleep and its disorder].", "content": "In rats, administration of anticholinesterase drugs (both the penetrating blood-brain barrier armin and the nonpenetrating preparation Gd-42) prevented the decrease of protein content in the neurons and glia of the supraoptic nucleus, as well as of RNA content in the neurons which usually occurred in intact animals after 24-hr deprivation of the REM sleep by the Jouvet method (also with partial disturbance of the slow wave phase).", "contents": "[Effect of anticholinesterase agents on the protein and RNA content in the cells of the supraoptic nucleus during sleep and its disorder]. In rats, administration of anticholinesterase drugs (both the penetrating blood-brain barrier armin and the nonpenetrating preparation Gd-42) prevented the decrease of protein content in the neurons and glia of the supraoptic nucleus, as well as of RNA content in the neurons which usually occurred in intact animals after 24-hr deprivation of the REM sleep by the Jouvet method (also with partial disturbance of the slow wave phase)."}
{"id": "PMID:202514", "title": "[Effect of ACTH and hydrocortisone on the functional state and interaction of brain structures].", "content": "In chronic experiments on cats ACTH facilitated the development of behavioral responses to gradually increasing electric stimulation of the medial hypothalamus, hippocampus and the midbrain reticular formation as well as potentiated the reticulo-hypothalamic influence. The effect of hydrocortisone was opposite. The reciprocal reticular and hormonal influences on the basal and anterior amygdala were revealed as well as some hormonal changes due to unspecific thalamic effects upon the limbic structures. The revealed systemic hormonal effect on the state and interaction of cerebral structures seems to be the base for integration of neural and hormonal mechanisms of some behavioral responses.", "contents": "[Effect of ACTH and hydrocortisone on the functional state and interaction of brain structures]. In chronic experiments on cats ACTH facilitated the development of behavioral responses to gradually increasing electric stimulation of the medial hypothalamus, hippocampus and the midbrain reticular formation as well as potentiated the reticulo-hypothalamic influence. The effect of hydrocortisone was opposite. The reciprocal reticular and hormonal influences on the basal and anterior amygdala were revealed as well as some hormonal changes due to unspecific thalamic effects upon the limbic structures. The revealed systemic hormonal effect on the state and interaction of cerebral structures seems to be the base for integration of neural and hormonal mechanisms of some behavioral responses."}
{"id": "PMID:202517", "title": "[Regulation of hormone receptor (author's transl)].", "content": "The regulation of hormone receptors is exerted through genetic and environmental factors. Genetic control of hormone receptors is analyzed by studying changes in their characteristics during the ontogeny, phylogeny, and malignant transformation of cells. The pattern of changes in glucocorticoid receptor contents in cytosol fraction during ontogeny is quite different from tissue to tissue. In the rat's lung tissue, glucocorticoid receptor contents are high during the fetal period and decrease promptly after birth, whereas the contents in the rat's liver are low during the fetal life and start to increase after birth. Glucocorticoid receptors in thymocytes of rats during T-cell differentiation increase transiently, which gives a high sensitivity to steroid treatment in the immature thymocytes. The induction of glucocorticoid receptors in different tissues at different stages of life is strictly controlled by the genetic program. Whether the induction is mediated by humoral factor(s) remains to be clarified. Amounts of glucocorticoid receptors in a particular tissue are subjected to species differences. In a group of steroid-sensitive animals such as the rat, mouse, rabbit and hamster, the amount of glucocorticoid receptors in liver sytosol is rich, whereas it is poor or undetectable in a group of steroid-resistant animals, such as the human, monkey, dog and guinea-pig. Changes in hormone receptors are also observed in malignant tumors. Under certain circumstances, hormone receptors \"appear\" in malignant tumors originated from organs in which no detectable hormone receptor is observed. These tumors may be called hormone receptor-producing tumors. Environmental factors are also important in regulating hormone receptors. Down regulation of hormone receptors is observed in insulin and glucocorticoids.", "contents": "[Regulation of hormone receptor (author's transl)]. The regulation of hormone receptors is exerted through genetic and environmental factors. Genetic control of hormone receptors is analyzed by studying changes in their characteristics during the ontogeny, phylogeny, and malignant transformation of cells. The pattern of changes in glucocorticoid receptor contents in cytosol fraction during ontogeny is quite different from tissue to tissue. In the rat's lung tissue, glucocorticoid receptor contents are high during the fetal period and decrease promptly after birth, whereas the contents in the rat's liver are low during the fetal life and start to increase after birth. Glucocorticoid receptors in thymocytes of rats during T-cell differentiation increase transiently, which gives a high sensitivity to steroid treatment in the immature thymocytes. The induction of glucocorticoid receptors in different tissues at different stages of life is strictly controlled by the genetic program. Whether the induction is mediated by humoral factor(s) remains to be clarified. Amounts of glucocorticoid receptors in a particular tissue are subjected to species differences. In a group of steroid-sensitive animals such as the rat, mouse, rabbit and hamster, the amount of glucocorticoid receptors in liver sytosol is rich, whereas it is poor or undetectable in a group of steroid-resistant animals, such as the human, monkey, dog and guinea-pig. Changes in hormone receptors are also observed in malignant tumors. Under certain circumstances, hormone receptors \"appear\" in malignant tumors originated from organs in which no detectable hormone receptor is observed. These tumors may be called hormone receptor-producing tumors. Environmental factors are also important in regulating hormone receptors. Down regulation of hormone receptors is observed in insulin and glucocorticoids."}
{"id": "PMID:202519", "title": "[Urinary excretion of 3beta-hydroxy-delta5-steroids in the newborn infant and the effect of ACTH administration (author's transl)].", "content": "The urinary 3beta-hydroxy-delta5-steroids excreted during the period of the first week by newborn infants were analyzed by means of gas chromatography and gas chromatography-mass spectrometry to study the changes in the amount of these steroids. The changes in the amount of each steroid after the administration of ACTH were also studied. The results are summarized as follows: 1) Seven kinds of 3beta-hydroxy-delta5-steroids were identified in the urine of the newborn infants. 17alpha, 21-dihydroxypregnenolone was newly identified. 2) The daily changes in the amount of each of these steroids differed. Generally, the amount of the C-19 steroids increased day by day and that of the C-21 steroids decreased during the period of our observation. 3) After the administration of ACTH, the amount of these urinary steroids excreted increased at nearly the same rate.", "contents": "[Urinary excretion of 3beta-hydroxy-delta5-steroids in the newborn infant and the effect of ACTH administration (author's transl)]. The urinary 3beta-hydroxy-delta5-steroids excreted during the period of the first week by newborn infants were analyzed by means of gas chromatography and gas chromatography-mass spectrometry to study the changes in the amount of these steroids. The changes in the amount of each steroid after the administration of ACTH were also studied. The results are summarized as follows: 1) Seven kinds of 3beta-hydroxy-delta5-steroids were identified in the urine of the newborn infants. 17alpha, 21-dihydroxypregnenolone was newly identified. 2) The daily changes in the amount of each of these steroids differed. Generally, the amount of the C-19 steroids increased day by day and that of the C-21 steroids decreased during the period of our observation. 3) After the administration of ACTH, the amount of these urinary steroids excreted increased at nearly the same rate."}
{"id": "PMID:202521", "title": "Cell-mediated cytotoxicity: comparison of primary and secondary immune reactions after parainfluenza type 1 virus inoculation.", "content": "H-2 antigen compatibility of effector spleen cells and target cells was necessary for cell-mediated cytotoxicity (CMC) after both 1 and 2 intraperitoneal inoculation of 6/94 virus into mice. T cells were responsible for both primary and secondary CMS reactions. Neither reaction was influenced by the presence of virus-specific antibody added to the test system. Secondary CMC peaked earlier than the primary response and declined more rapidly. In vitro stimulation of primed spleen cells could also be used to detect the secondary CMC response.", "contents": "Cell-mediated cytotoxicity: comparison of primary and secondary immune reactions after parainfluenza type 1 virus inoculation. H-2 antigen compatibility of effector spleen cells and target cells was necessary for cell-mediated cytotoxicity (CMC) after both 1 and 2 intraperitoneal inoculation of 6/94 virus into mice. T cells were responsible for both primary and secondary CMS reactions. Neither reaction was influenced by the presence of virus-specific antibody added to the test system. Secondary CMC peaked earlier than the primary response and declined more rapidly. In vitro stimulation of primed spleen cells could also be used to detect the secondary CMC response."}
{"id": "PMID:202522", "title": "Cell-mediated immunity to vesicular stomatitis virus infections in mice.", "content": "The T cell-mediated immune responses of mice against vesicular stomatitis virus (VSV) were assessed by measuring direct primary foot pad swelling after local VSV infection and cytotoxic activity in spleens. The cytolytic activity was mediated by T cells since it was anti-theta + complement sensitive, was restricted by the K and D region but not the I region of H-2 and rapidly increased after 4 days but decreased 8 days after systemic or local infection. Cytolytic activity was virus-specific as reciprocally tested with VSV and vaccina virus immune T cells. Measurable activity on day 7 depended on infectious virus dose, virus virulence, and non-H-2 genetic background of the host. More than half of the cytolytic activity wasblocked specifically by either immune anti-H2 or rabbit anti-VSV antisera. Analysis of the kinetics of appearance of antigenic changes using metabolic inhibitors, revealed that the changes that rendered target cells susceptible to lysis after infection, occurred within the first hour after infection.", "contents": "Cell-mediated immunity to vesicular stomatitis virus infections in mice. The T cell-mediated immune responses of mice against vesicular stomatitis virus (VSV) were assessed by measuring direct primary foot pad swelling after local VSV infection and cytotoxic activity in spleens. The cytolytic activity was mediated by T cells since it was anti-theta + complement sensitive, was restricted by the K and D region but not the I region of H-2 and rapidly increased after 4 days but decreased 8 days after systemic or local infection. Cytolytic activity was virus-specific as reciprocally tested with VSV and vaccina virus immune T cells. Measurable activity on day 7 depended on infectious virus dose, virus virulence, and non-H-2 genetic background of the host. More than half of the cytolytic activity wasblocked specifically by either immune anti-H2 or rabbit anti-VSV antisera. Analysis of the kinetics of appearance of antigenic changes using metabolic inhibitors, revealed that the changes that rendered target cells susceptible to lysis after infection, occurred within the first hour after infection."}
{"id": "PMID:202531", "title": "Gangliosides of active and inactive neuroblastoma clones.", "content": "It is possible to divide neuroblastoma cells into clones able to synthesize neurotransmitters (active clones) or not (inactive clones). The analysis of gangliosides of active and inactive clones shows that their total lipid sialic acids is markedly lower than that of neuron-enriched fractions prepared from brain. The ganglioside pattern of the cultured cells also differs notably from those obtained with neuronal fractions from brain. The absence of tri- and tetrasialogangliosides and the presence of appreciable amounts of the simplest monosialogangliosides are particularly noticeable in the neuroblastoma. Morphological differentiation obtained by serum deprivation, dibutyryl cyclic AMP or bromodeoxyuridine does not restore a true neuronal pattern. Gangliosides could not therefore be used as a marker of neuronal differentiation in this type of cell. No correlations can be found between the ganglioside pattern and the ability of cells to synthesize neurotransmitters.", "contents": "Gangliosides of active and inactive neuroblastoma clones. It is possible to divide neuroblastoma cells into clones able to synthesize neurotransmitters (active clones) or not (inactive clones). The analysis of gangliosides of active and inactive clones shows that their total lipid sialic acids is markedly lower than that of neuron-enriched fractions prepared from brain. The ganglioside pattern of the cultured cells also differs notably from those obtained with neuronal fractions from brain. The absence of tri- and tetrasialogangliosides and the presence of appreciable amounts of the simplest monosialogangliosides are particularly noticeable in the neuroblastoma. Morphological differentiation obtained by serum deprivation, dibutyryl cyclic AMP or bromodeoxyuridine does not restore a true neuronal pattern. Gangliosides could not therefore be used as a marker of neuronal differentiation in this type of cell. No correlations can be found between the ganglioside pattern and the ability of cells to synthesize neurotransmitters."}
{"id": "PMID:202532", "title": "An attempt to differentiate selection and amplification in hormone receptor development: the unicellular model.", "content": "Earlier experiments demonstrated that a membrane pattern of Protozoa behaves as a receptor with respect to hormones of higher organisms. This raised the possibility that some selection or strengthening of this unspecific patter is involved in the evolution of the specific membrane patterns of the individual cells of higher organisms. In the present experiments, as a result of continual histamine treatment, the phagocytotic ability of a population of Tetrahymena was increased more intensely than after a single histamine treatment. The phagocytotic rate remained high for some time after the animals were returned from histamine-containing to normal medium. Thus, from the experimental data, it appears likely that as the hormone appears, selection becomes involved in the proliferation of cells possessing receptors. This observation might not only be of phylogenetic interest, but could also be relevant in receptor maturation as manifested in ontogenetic membrane differentiation.", "contents": "An attempt to differentiate selection and amplification in hormone receptor development: the unicellular model. Earlier experiments demonstrated that a membrane pattern of Protozoa behaves as a receptor with respect to hormones of higher organisms. This raised the possibility that some selection or strengthening of this unspecific patter is involved in the evolution of the specific membrane patterns of the individual cells of higher organisms. In the present experiments, as a result of continual histamine treatment, the phagocytotic ability of a population of Tetrahymena was increased more intensely than after a single histamine treatment. The phagocytotic rate remained high for some time after the animals were returned from histamine-containing to normal medium. Thus, from the experimental data, it appears likely that as the hormone appears, selection becomes involved in the proliferation of cells possessing receptors. This observation might not only be of phylogenetic interest, but could also be relevant in receptor maturation as manifested in ontogenetic membrane differentiation."}
{"id": "PMID:202533", "title": "Immunosupressive activity of the basic protein from tumor tissue.", "content": "The basic protein prepared from AH-130 ascites hepatoma cells was tested for its effect on the cell-mediated immune response of Donryu strain rats. The basic protein suppressed the response of peripheral and lymph node lymphocytes to phytohemagglutinin and lymphocyte trapping in the antigen-draining lymph node. These results indicated that the basic protein from tumor tissue possibly had an immunosuppressive activity and affected inadequately the cell-mediated immune response as usually observed in tumor-bearing hosts.", "contents": "Immunosupressive activity of the basic protein from tumor tissue. The basic protein prepared from AH-130 ascites hepatoma cells was tested for its effect on the cell-mediated immune response of Donryu strain rats. The basic protein suppressed the response of peripheral and lymph node lymphocytes to phytohemagglutinin and lymphocyte trapping in the antigen-draining lymph node. These results indicated that the basic protein from tumor tissue possibly had an immunosuppressive activity and affected inadequately the cell-mediated immune response as usually observed in tumor-bearing hosts."}
{"id": "PMID:202534", "title": "Hematological alterations in tumor-bearing rats, with reference to pathogenesis of chronic type of disseminated intravascular coagulation syndrome.", "content": "Hematological studied were carried out serially in the rats transplanted subcutaneously with Yoshida ascites hepatoma AH-109A. Significant changes were observed in fibrinogen level, fibrinogen degradation products, recalcification time, platelet count, and fragmentation of red blood cells. Formation of thrombi was revealed in the vessels of tumor tissue morphologically from early stage when the tumor grew to a palpable size. Thrombi were formed also in the arterioles of the lungs in the terminal stage. Bleeding tendency was noted in some cases at death. These findings suggested the experimental induction of a type of disseminated intravascular coagulation. The systemic changes of the blood occurring in the terminal stage were preceded by localized intravascular coagulation and fibrinolysis in the tumor in early stage of tumor growth.", "contents": "Hematological alterations in tumor-bearing rats, with reference to pathogenesis of chronic type of disseminated intravascular coagulation syndrome. Hematological studied were carried out serially in the rats transplanted subcutaneously with Yoshida ascites hepatoma AH-109A. Significant changes were observed in fibrinogen level, fibrinogen degradation products, recalcification time, platelet count, and fragmentation of red blood cells. Formation of thrombi was revealed in the vessels of tumor tissue morphologically from early stage when the tumor grew to a palpable size. Thrombi were formed also in the arterioles of the lungs in the terminal stage. Bleeding tendency was noted in some cases at death. These findings suggested the experimental induction of a type of disseminated intravascular coagulation. The systemic changes of the blood occurring in the terminal stage were preceded by localized intravascular coagulation and fibrinolysis in the tumor in early stage of tumor growth."}
{"id": "PMID:202535", "title": "Effect of 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea on experimental tumors.", "content": "A newly synthesized water-soluble nitrosourea derivative, 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU; NSC-254157) has marked activities against experimental tumors such as lymphoid leukemia L-1210, ascites sarcoma- 180, ascites hepatoma AH-130, and Walker carcinosarcoma-256. A single intraperitoneal injection of the compound is more effective than successive injections on the L-1210 system. An especially interesting point is that both the single intraperitoneal and single oral administrations 2 days after tumor implantation showed a high effectiveness. In addition, growth of the mammary adenocarcinoma transplanted subcutaneously on the back of mice was also considerably suppressed by successive intraperitoneal injections of the compound.", "contents": "Effect of 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea on experimental tumors. A newly synthesized water-soluble nitrosourea derivative, 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU; NSC-254157) has marked activities against experimental tumors such as lymphoid leukemia L-1210, ascites sarcoma- 180, ascites hepatoma AH-130, and Walker carcinosarcoma-256. A single intraperitoneal injection of the compound is more effective than successive injections on the L-1210 system. An especially interesting point is that both the single intraperitoneal and single oral administrations 2 days after tumor implantation showed a high effectiveness. In addition, growth of the mammary adenocarcinoma transplanted subcutaneously on the back of mice was also considerably suppressed by successive intraperitoneal injections of the compound."}
{"id": "PMID:202536", "title": "Evaluation on the recurrent cases of early gastric carcinoma.", "content": "In the First Department of Surgery, Faculty of Medicine, Chiba University, 213 cases with early gastric carcinoma have undergone an excision from 1955 to 1975. The observed 5-year, relative 5-year, observed 10-year, and relative 10-year survival rates of these cases amount to 89.3%, 99.8% and 98.0% respectively. The present investigation concerns 13 of these patients with diagnosed postoperative recurrent cases. The post-operative gastric carcinima recurrence might be classified to metastasis to liver and lymphnodes, peritoneal dissemination, residual gastric recurrence and recurrence in miscellaneous organs. The 13 cases involved 2 cases of liver metastasis, 9 cases of residual gastric recurrence and 2 cases of recurrence in miscellaneous organs. Nine of these cases underwent re-operations which were grouped to 6 cases of residual gastrectomy, 2 cases of excision of miscellaneous organs (cecum and rectum), and 1 case exploratory laparotomy. The development in the cases is characterized by 3 cases of stump persistent carcinoma at the residual stomach due to stump carcinoma positive in excision, 2 cases of residual gastric carcinoma due to lymphatic vessel invasion and 6 cases of multiple carcinoma.", "contents": "Evaluation on the recurrent cases of early gastric carcinoma. In the First Department of Surgery, Faculty of Medicine, Chiba University, 213 cases with early gastric carcinoma have undergone an excision from 1955 to 1975. The observed 5-year, relative 5-year, observed 10-year, and relative 10-year survival rates of these cases amount to 89.3%, 99.8% and 98.0% respectively. The present investigation concerns 13 of these patients with diagnosed postoperative recurrent cases. The post-operative gastric carcinima recurrence might be classified to metastasis to liver and lymphnodes, peritoneal dissemination, residual gastric recurrence and recurrence in miscellaneous organs. The 13 cases involved 2 cases of liver metastasis, 9 cases of residual gastric recurrence and 2 cases of recurrence in miscellaneous organs. Nine of these cases underwent re-operations which were grouped to 6 cases of residual gastrectomy, 2 cases of excision of miscellaneous organs (cecum and rectum), and 1 case exploratory laparotomy. The development in the cases is characterized by 3 cases of stump persistent carcinoma at the residual stomach due to stump carcinoma positive in excision, 2 cases of residual gastric carcinoma due to lymphatic vessel invasion and 6 cases of multiple carcinoma."}
{"id": "PMID:202537", "title": "Methadone blockade of 2-deoxyglucose-induced pancreatic secretion in the rat.", "content": "The effects of methadone on pancreatic exocrine secretions in the rat were tested under basal conditions and after hormonal stimulation by secretin and caerulein or after stimulation of the differentially acting cholinergic agents acetylcholine, 2-deoxyglucose, and electrical stimulation of the vagus. Methadone had no effect on basal hydroelectrolytic secretion. It decreased basal enzyme secretion very slightly under our experimental conditions. The stimulatory effects of 75 mg of 2-deoxyglucose per kg were completely blocked by methadone at 5 mg per kg and this blockade was reversed by nalorphine at 6 to 9 mg per kg. It was found that there are doses of methadone (100 microgram) which block 2-deoxyglucose effects when injected into brain ventricles but are ineffective when systemically introduced. The effects of secretin, caerulein, acetylcholine, and electrical stimulation of the vagus were not depressed by methadone. These results strongly suggest that the methadone blockade of 2-deoxyglucose effects occurs at a central level and is mediated by narcotic drug receptors.", "contents": "Methadone blockade of 2-deoxyglucose-induced pancreatic secretion in the rat. The effects of methadone on pancreatic exocrine secretions in the rat were tested under basal conditions and after hormonal stimulation by secretin and caerulein or after stimulation of the differentially acting cholinergic agents acetylcholine, 2-deoxyglucose, and electrical stimulation of the vagus. Methadone had no effect on basal hydroelectrolytic secretion. It decreased basal enzyme secretion very slightly under our experimental conditions. The stimulatory effects of 75 mg of 2-deoxyglucose per kg were completely blocked by methadone at 5 mg per kg and this blockade was reversed by nalorphine at 6 to 9 mg per kg. It was found that there are doses of methadone (100 microgram) which block 2-deoxyglucose effects when injected into brain ventricles but are ineffective when systemically introduced. The effects of secretin, caerulein, acetylcholine, and electrical stimulation of the vagus were not depressed by methadone. These results strongly suggest that the methadone blockade of 2-deoxyglucose effects occurs at a central level and is mediated by narcotic drug receptors."}
{"id": "PMID:202545", "title": "The histoenzymic activity of gyrus cinguli in the course of postnatal ontogeny of the rat.", "content": "Histochemical investigations concerning the activity of several dehydrogenases and hydrolases in the area cinguli during postnatal ontogenic development of the rat were performed. Brain sections corresponding to the region of area cinguli, obtained from rats aged 1, 3, 8, 17, 40 and 60 days postnatal, were subjected to histochemical assays for various dehydrogenases, phosphatases and esterases. The developmental changes concerning histoenzymic reactivity of the callosal gyrus with regard to several respiratory and hydrolytic enzymes were assessed and described. Considerable differences in enzymic reactivity, appertaining particularly to the phosphatases and esterases, between the anterior and posterior parts of the callosal gyrus were found. The unusual enzymic reactivity of glial cells in the individual regions of the area cinguli has been pointed out.", "contents": "The histoenzymic activity of gyrus cinguli in the course of postnatal ontogeny of the rat. Histochemical investigations concerning the activity of several dehydrogenases and hydrolases in the area cinguli during postnatal ontogenic development of the rat were performed. Brain sections corresponding to the region of area cinguli, obtained from rats aged 1, 3, 8, 17, 40 and 60 days postnatal, were subjected to histochemical assays for various dehydrogenases, phosphatases and esterases. The developmental changes concerning histoenzymic reactivity of the callosal gyrus with regard to several respiratory and hydrolytic enzymes were assessed and described. Considerable differences in enzymic reactivity, appertaining particularly to the phosphatases and esterases, between the anterior and posterior parts of the callosal gyrus were found. The unusual enzymic reactivity of glial cells in the individual regions of the area cinguli has been pointed out."}
{"id": "PMID:202546", "title": "The activity of some intracellular oxidative enzymes in the thyroid follicular epithelium of Xenopus laevis Daud. in experimental long-term hypokinesia.", "content": "Histoenzymological methods were applied to examine the activities of previously little studied intracellular oxidative enzymes in the cells of the thyroid follicular epithelium of Xenopus laevis Daud. specimens kept in aquarium. Succinate, lactate, alpha-glycerophosphate, glucose-6-phosphate and reduced NAD and NADP dehydrogenases and cytochrome oxidase were studied. In comparison with other chordate species a very strong activity was revealed particularly by lactate dehydrogenase. The data obtained suggest that the metabolism in thyroid cells of the motionless Xenopus is based on glycolysis mainly.", "contents": "The activity of some intracellular oxidative enzymes in the thyroid follicular epithelium of Xenopus laevis Daud. in experimental long-term hypokinesia. Histoenzymological methods were applied to examine the activities of previously little studied intracellular oxidative enzymes in the cells of the thyroid follicular epithelium of Xenopus laevis Daud. specimens kept in aquarium. Succinate, lactate, alpha-glycerophosphate, glucose-6-phosphate and reduced NAD and NADP dehydrogenases and cytochrome oxidase were studied. In comparison with other chordate species a very strong activity was revealed particularly by lactate dehydrogenase. The data obtained suggest that the metabolism in thyroid cells of the motionless Xenopus is based on glycolysis mainly."}
{"id": "PMID:202547", "title": "[Contractile responses of the guinea pig ileal longitudinal muscle to antispasmodics (author's transl)].", "content": "Papaverine, benactyzine and Aspaminol were found to induce strong contractions of guinea pig ileal longitudinal muscle in a medium containing 3.2 mM of Ca2+. The contractile actions of papaverine, benactyzine and Aspaminol were potentiated with increase in Ca2+. The contractile actions of papaverine, benactyzine and action of papaverine was completely blocked by Mn2+, which by itself caused a contraction of the longitudinal muscle. The maximal contraction by papaverine was obtained at the concentration of more than 10(-5) M, WHILE BOTH BENACTYZINE AND Aspaminol induced the maximal contractions at the concentration of 3 X 10(-4) M. During and after the contraction by papaverine, contractile responses to benactyzine and Aspaminol were not observed. Changes in the intracellular level of cyclic GMP after exposure of the longitudinal muscle to papaverine, benactyzine or Aspaminol did not occur. These results suggest that papaverine, benactyzine Aspaminol may induce contractions of the ileal longitudinal muscle through a similar mechanism of action. A likely assumption is that these drugs move intracellular bound Ca2+ to the contractile protein of the muscle.", "contents": "[Contractile responses of the guinea pig ileal longitudinal muscle to antispasmodics (author's transl)]. Papaverine, benactyzine and Aspaminol were found to induce strong contractions of guinea pig ileal longitudinal muscle in a medium containing 3.2 mM of Ca2+. The contractile actions of papaverine, benactyzine and Aspaminol were potentiated with increase in Ca2+. The contractile actions of papaverine, benactyzine and action of papaverine was completely blocked by Mn2+, which by itself caused a contraction of the longitudinal muscle. The maximal contraction by papaverine was obtained at the concentration of more than 10(-5) M, WHILE BOTH BENACTYZINE AND Aspaminol induced the maximal contractions at the concentration of 3 X 10(-4) M. During and after the contraction by papaverine, contractile responses to benactyzine and Aspaminol were not observed. Changes in the intracellular level of cyclic GMP after exposure of the longitudinal muscle to papaverine, benactyzine or Aspaminol did not occur. These results suggest that papaverine, benactyzine Aspaminol may induce contractions of the ileal longitudinal muscle through a similar mechanism of action. A likely assumption is that these drugs move intracellular bound Ca2+ to the contractile protein of the muscle."}
{"id": "PMID:202549", "title": "Non-functioning islet cell tumours of the pancreas: a review of radiological literature and a report on two cases.", "content": "Two cases of endocrine inactive malignant islet cell tumors diagnosed by angiography are presented. The angiographic features are described and the differential diagnosis of the tumor and its metastases are discussed. Radiological literature of the past decade on this subject is reviewed.", "contents": "Non-functioning islet cell tumours of the pancreas: a review of radiological literature and a report on two cases. Two cases of endocrine inactive malignant islet cell tumors diagnosed by angiography are presented. The angiographic features are described and the differential diagnosis of the tumor and its metastases are discussed. Radiological literature of the past decade on this subject is reviewed."}
{"id": "PMID:202550", "title": "[The treatment of severe and recurrent nonspecific colpitis].", "content": "Attention is drawn to the incidence of colpitis and the symptom of \"vaginal discharge\" in the gynaecological field, as well as to the required investigations as far as differential diagnosis is concerned. Severe, purulent, unspecific colpitis and also recurrent colpitis require particularly careful treatment. Excellent therapeutic results have been achieved over many years with repeated local administration of TC-Gel-Steraject and, if necessary, additional treatment with an oestriol preparation; this therapy is therefore recommended.", "contents": "[The treatment of severe and recurrent nonspecific colpitis]. Attention is drawn to the incidence of colpitis and the symptom of \"vaginal discharge\" in the gynaecological field, as well as to the required investigations as far as differential diagnosis is concerned. Severe, purulent, unspecific colpitis and also recurrent colpitis require particularly careful treatment. Excellent therapeutic results have been achieved over many years with repeated local administration of TC-Gel-Steraject and, if necessary, additional treatment with an oestriol preparation; this therapy is therefore recommended."}
{"id": "PMID:202557", "title": "Regulation of lipolysis in adipose tissue.", "content": "The normal human or animal has a series of finely coordinated and overlapping control mechanisms that regulate the storage or release of fat according to the overall energy requirements of the body. We have examined only one side of this system, the part responsible for the release of fatty acids from adipose tissue. Considerable information is available on the extracellular factors that control lipolysis on a minute-to-minute or day-to-day basis, but less is known about long-term regulation or about the precise role of intracellular factors that almost surely condition the response of the fat cell to external stimuli. When one poses the question of what determines the overall fat mass or adiposity of an individual, even less is known. Psychogenic factors regulating food intake, circulating hormonal signals, and local regulators of metabolism in the adipose tissue may all play a role. This remains an intriguing but elusive problem to be answered by future research.", "contents": "Regulation of lipolysis in adipose tissue. The normal human or animal has a series of finely coordinated and overlapping control mechanisms that regulate the storage or release of fat according to the overall energy requirements of the body. We have examined only one side of this system, the part responsible for the release of fatty acids from adipose tissue. Considerable information is available on the extracellular factors that control lipolysis on a minute-to-minute or day-to-day basis, but less is known about long-term regulation or about the precise role of intracellular factors that almost surely condition the response of the fat cell to external stimuli. When one poses the question of what determines the overall fat mass or adiposity of an individual, even less is known. Psychogenic factors regulating food intake, circulating hormonal signals, and local regulators of metabolism in the adipose tissue may all play a role. This remains an intriguing but elusive problem to be answered by future research."}
{"id": "PMID:202565", "title": "The effect of attapulgite and charcoal on enterotoxicity of Vibrio cholerae and Escherichia coli enterotoxins in rabbits.", "content": "Vibrio cholerae and certain strains of Escherichia coli produce heat-labile enterotoxins which play a significant role in the pathogenesis of the intestinal disease. Activated attapulgite, a heated magnesium aluminum silicate, was previously shown to prevent the toxic effects of endotoxin. The present study has revealed that this drug inhibits the toxic effects of cholera and E. coli enterotoxins in the intestinal loop of rabbits, when toxin and attapulgite are pre-incubated prior to injection. Up to 50 to 100 minimal effective doses are inhibited. Attapulgite is effective also when injected separately, albeit simultaneously, into the intestinal loops, but not when administered after the toxin. Since supernates of toxinattapulgite mixtures are non-toxic, it is postulated that attapulgite acts by adsorption and that the attached enterotoxin is no longer toxic to the rabbit intestine. The previously reported effect of charcoal on V. cholerae enterotoxin paralleling that of attapulgite, was confirmed. In contrast to the effects of these absorbents on isolated toxin, both failed to prevent enterotoxicity in the rabbit model of an enterotoxin-producing strain of E. coli.", "contents": "The effect of attapulgite and charcoal on enterotoxicity of Vibrio cholerae and Escherichia coli enterotoxins in rabbits. Vibrio cholerae and certain strains of Escherichia coli produce heat-labile enterotoxins which play a significant role in the pathogenesis of the intestinal disease. Activated attapulgite, a heated magnesium aluminum silicate, was previously shown to prevent the toxic effects of endotoxin. The present study has revealed that this drug inhibits the toxic effects of cholera and E. coli enterotoxins in the intestinal loop of rabbits, when toxin and attapulgite are pre-incubated prior to injection. Up to 50 to 100 minimal effective doses are inhibited. Attapulgite is effective also when injected separately, albeit simultaneously, into the intestinal loops, but not when administered after the toxin. Since supernates of toxinattapulgite mixtures are non-toxic, it is postulated that attapulgite acts by adsorption and that the attached enterotoxin is no longer toxic to the rabbit intestine. The previously reported effect of charcoal on V. cholerae enterotoxin paralleling that of attapulgite, was confirmed. In contrast to the effects of these absorbents on isolated toxin, both failed to prevent enterotoxicity in the rabbit model of an enterotoxin-producing strain of E. coli."}
{"id": "PMID:202566", "title": "Acute encephalopathy with liver dysfunction, chylous ascites and cytomegalovirus infection.", "content": "A child with acute encephalopathy and liver dysfunction subsequently developed acute chylous ascites. Titers for cytomegalovirus increased from less than 1:2 to 1:32 during the illness, and cytomegalovirus was isolated from the urine. The case is the first one possibly linking cytomegalovirus and acute encephalopathy and liver dysfunction in a child. In our patient, enlargement of the abdominal lymph nodes, as seen on a lymphangiogram, resulted in a severe obstruction of abdominal lymphatic flow, producing a transudation of lymph into the peritoneal cavity. The acute chylous ascites associated with mesenteric lymphadenitis was likely caused by the cytomegalovirus infection.", "contents": "Acute encephalopathy with liver dysfunction, chylous ascites and cytomegalovirus infection. A child with acute encephalopathy and liver dysfunction subsequently developed acute chylous ascites. Titers for cytomegalovirus increased from less than 1:2 to 1:32 during the illness, and cytomegalovirus was isolated from the urine. The case is the first one possibly linking cytomegalovirus and acute encephalopathy and liver dysfunction in a child. In our patient, enlargement of the abdominal lymph nodes, as seen on a lymphangiogram, resulted in a severe obstruction of abdominal lymphatic flow, producing a transudation of lymph into the peritoneal cavity. The acute chylous ascites associated with mesenteric lymphadenitis was likely caused by the cytomegalovirus infection."}
{"id": "PMID:202569", "title": "Transformation of human cells by temperature-sensitive mutants of simian virus-40.", "content": "Conditions necessary for the establishment and maintenance of transformation of human cells by wild type and temperature-sensitive mutants of SV40 were examined. For both early and late mutants, the frequency of transformation was found to be up to 5-fold higher, and virus yield 100-fold lower, at 39 degrees than at 33 degrees. No such effect was observed with the wild type virus under the same conditions. This observation is apparently at variance with previously published work, but may be explained by the semipermissive nature of the cells that we used. Increasing the temperature to 40.5 degrees caused cells transformed by the early mutant, tsA30, to lose T-antigen as detectable by staining, and also to lose the ability to grow to high density, while it produced no effect on cells transformed by wild type virus.", "contents": "Transformation of human cells by temperature-sensitive mutants of simian virus-40. Conditions necessary for the establishment and maintenance of transformation of human cells by wild type and temperature-sensitive mutants of SV40 were examined. For both early and late mutants, the frequency of transformation was found to be up to 5-fold higher, and virus yield 100-fold lower, at 39 degrees than at 33 degrees. No such effect was observed with the wild type virus under the same conditions. This observation is apparently at variance with previously published work, but may be explained by the semipermissive nature of the cells that we used. Increasing the temperature to 40.5 degrees caused cells transformed by the early mutant, tsA30, to lose T-antigen as detectable by staining, and also to lose the ability to grow to high density, while it produced no effect on cells transformed by wild type virus."}
{"id": "PMID:202570", "title": "Virus shedding by SV40-transformed human cells.", "content": "Cultures of human cells transformed by SV40 were found to release infectious virus, even after several passages in vitro. Virus shedding by these cultures did not depend on propagation of virus from cell to cell, as it was not affected by anti-SV40 antiserum that could effectively block virus propagation in acutely infected cells. Cells transformed by the 'early' temperature-sensitive mutant tsA30, and maintained at the restrictive temperature of 39 degrees, shed virus in reduced amount. Finally, xeroderma pigmentosum cells transformed by SV40 were also found to release virus, indicating that the enzymes of excision and repair of UV-induced damage to DNA probably were not involved in the molecular mechanism underlying virus shedding.", "contents": "Virus shedding by SV40-transformed human cells. Cultures of human cells transformed by SV40 were found to release infectious virus, even after several passages in vitro. Virus shedding by these cultures did not depend on propagation of virus from cell to cell, as it was not affected by anti-SV40 antiserum that could effectively block virus propagation in acutely infected cells. Cells transformed by the 'early' temperature-sensitive mutant tsA30, and maintained at the restrictive temperature of 39 degrees, shed virus in reduced amount. Finally, xeroderma pigmentosum cells transformed by SV40 were also found to release virus, indicating that the enzymes of excision and repair of UV-induced damage to DNA probably were not involved in the molecular mechanism underlying virus shedding."}
{"id": "PMID:202571", "title": "Factors affecting the interferon sensitivity of human cytomegalovirus.", "content": "Several factors affected the interferon sensitivity of human cytomegalovirus in human foreskin fibroblast cultures. An inoculum of infected cells was up to 300-fold less sensitive than a cell-free inoculum of equivalent input multiplicity. A 10-fold increase in the dose of infectious units of either type of inoculum was associated with a 10-fold or greater decrease in interferon sensitivity. Several aspects of the virus-cell interaction were examined and parameters indicative of cell infection were less inhibited by interferon than were those for virus replication.", "contents": "Factors affecting the interferon sensitivity of human cytomegalovirus. Several factors affected the interferon sensitivity of human cytomegalovirus in human foreskin fibroblast cultures. An inoculum of infected cells was up to 300-fold less sensitive than a cell-free inoculum of equivalent input multiplicity. A 10-fold increase in the dose of infectious units of either type of inoculum was associated with a 10-fold or greater decrease in interferon sensitivity. Several aspects of the virus-cell interaction were examined and parameters indicative of cell infection were less inhibited by interferon than were those for virus replication."}
{"id": "PMID:202572", "title": "A simple method for concentration of enteroviruses and rotaviruses from cell culture harvests using membrane filters.", "content": "Organic compounds in cell culture harvests known as membrane-coating components (MCC) prevent virus adsorption to membrane filters. Blending cell culture harvests with fluorocarbon removed the MCC and permitted adsorption of virus in acidified harvests to epoxy-fiberglass filters. Subsequent elution with high pH buffer resulted in recovery of greater than 90% of the virus with concentrations of up to 100-fold.", "contents": "A simple method for concentration of enteroviruses and rotaviruses from cell culture harvests using membrane filters. Organic compounds in cell culture harvests known as membrane-coating components (MCC) prevent virus adsorption to membrane filters. Blending cell culture harvests with fluorocarbon removed the MCC and permitted adsorption of virus in acidified harvests to epoxy-fiberglass filters. Subsequent elution with high pH buffer resulted in recovery of greater than 90% of the virus with concentrations of up to 100-fold."}
{"id": "PMID:202573", "title": "Epidemic of hand, foot and mouth disease associated with enterovirus 71 infection.", "content": "Viruses isolated from patients with hand, foot and mouth disease in widespread outbreaks in Japan in 1973 were identified as enterovirus 71. Although cases with aseptic meningitis were observed concurrently, the main clinical symptom associated with enterovirus 71 infection was hand, foot and mouth disease.", "contents": "Epidemic of hand, foot and mouth disease associated with enterovirus 71 infection. Viruses isolated from patients with hand, foot and mouth disease in widespread outbreaks in Japan in 1973 were identified as enterovirus 71. Although cases with aseptic meningitis were observed concurrently, the main clinical symptom associated with enterovirus 71 infection was hand, foot and mouth disease."}
{"id": "PMID:202574", "title": "Ribosomal proteins in normal simian cells, SV40-transformed simian cells, and simian cells infected with SV40, adenovirus 5, and vesicular stomatitis virus.", "content": "The protein patterns of monosomes and polysomes isolated from the T-22 line of SV40-transformed GMK cells and from uninfected CV-1 cells and CV-1 cells infected with SV40, adenovirus 5, or vesicular stomatitis virus were analyzed by two-dimensional PAGE. All gel patterns were similar except for the presence of one additional protein associated with T-22 monosomes.", "contents": "Ribosomal proteins in normal simian cells, SV40-transformed simian cells, and simian cells infected with SV40, adenovirus 5, and vesicular stomatitis virus. The protein patterns of monosomes and polysomes isolated from the T-22 line of SV40-transformed GMK cells and from uninfected CV-1 cells and CV-1 cells infected with SV40, adenovirus 5, or vesicular stomatitis virus were analyzed by two-dimensional PAGE. All gel patterns were similar except for the presence of one additional protein associated with T-22 monosomes."}
{"id": "PMID:202575", "title": "The structural polypeptides of equine infections anemia virus.", "content": "The structural polypeptides and glycoproteins of equine infectious anemia virus were identified following electrophoresis in SDS-PAGE. The major non-glycosylated polypeptides had molecular weights of 25,000, 14,000 and 11,000 daltons. Two glycoproteins of 80,000 and 40,000 daltons were also detected. The relationship of these components to the structural elements of mammalian C-type oncoviruses is discussed.", "contents": "The structural polypeptides of equine infections anemia virus. The structural polypeptides and glycoproteins of equine infectious anemia virus were identified following electrophoresis in SDS-PAGE. The major non-glycosylated polypeptides had molecular weights of 25,000, 14,000 and 11,000 daltons. Two glycoproteins of 80,000 and 40,000 daltons were also detected. The relationship of these components to the structural elements of mammalian C-type oncoviruses is discussed."}
{"id": "PMID:202576", "title": "A new lymphoid cell line, Reh 6, with characteristics of non-T and non-B cells, lacking the Epstein-Barr virus genome and derived from human acute lymphoblastic leukemia.", "content": "A new lymphoid cell line, Reh 6, has been established from the peripheral blood of a patient with acute lymphocytic leukemia. Reh 6 cells were assayed for the presence of Epstein-Barr virus (EBV) DNA by nucleic acid hybridization and for Epstein-Barr nuclear antigen (EBNA) by the immunofluorescence test. Reassociation kinetics between in vitro [3H]-labeled EBV DNA and Reh 6 cell DNA indicated the absence of detectable amounts of EBV DNA in Reh 6 cell DNA. In addition, attempts to detect EBNA by the immunofluorescence test in Reh 6 cells were unsuccessful. Thus, this new lymphoid cell line apparently lacks the EBV genome.", "contents": "A new lymphoid cell line, Reh 6, with characteristics of non-T and non-B cells, lacking the Epstein-Barr virus genome and derived from human acute lymphoblastic leukemia. A new lymphoid cell line, Reh 6, has been established from the peripheral blood of a patient with acute lymphocytic leukemia. Reh 6 cells were assayed for the presence of Epstein-Barr virus (EBV) DNA by nucleic acid hybridization and for Epstein-Barr nuclear antigen (EBNA) by the immunofluorescence test. Reassociation kinetics between in vitro [3H]-labeled EBV DNA and Reh 6 cell DNA indicated the absence of detectable amounts of EBV DNA in Reh 6 cell DNA. In addition, attempts to detect EBNA by the immunofluorescence test in Reh 6 cells were unsuccessful. Thus, this new lymphoid cell line apparently lacks the EBV genome."}
{"id": "PMID:202577", "title": "Chicken embyro lethal orphan (CELO) virus DNA present in hamster cell lines derived from CELO-induced hepatomas.", "content": "The kinetics of renaturation of the isolated DNA fragments of chicken embryo lethal orphan (CELO) virus generated by the restriction enzyme EcoR1 was measured in the presence of DNA extracted from two lines of CELO virus-induced hamster hepatoma cells and from control hamster cells. One hepatoma cell line (CILT-2), which did not produce the CELO virus tumor (T) antigen, lacked sequences from about one-half the virus genome while the other hepatoma cell line (CEHEP), which did produce the CELO virus T antigen, lacked sequences corresponding to one-fifth of the viral genome.", "contents": "Chicken embyro lethal orphan (CELO) virus DNA present in hamster cell lines derived from CELO-induced hepatomas. The kinetics of renaturation of the isolated DNA fragments of chicken embryo lethal orphan (CELO) virus generated by the restriction enzyme EcoR1 was measured in the presence of DNA extracted from two lines of CELO virus-induced hamster hepatoma cells and from control hamster cells. One hepatoma cell line (CILT-2), which did not produce the CELO virus tumor (T) antigen, lacked sequences from about one-half the virus genome while the other hepatoma cell line (CEHEP), which did produce the CELO virus T antigen, lacked sequences corresponding to one-fifth of the viral genome."}
{"id": "PMID:202578", "title": "Effect of thymic humoral factor on intracellular levels of cyclic AMP in human peripheral blood lymphocytes.", "content": "The exposure of human peripheral blood lymphocytes to thymus hormone causes an increase in the intracellular cyclic AMP level in these cells. Studies of the thymus-hormone-induced changes in cellular cyclic AMP levels revealed that cord blood lymphocytes contain significantly more target cells for the hormone than adult peripheral blood lymphocytes. The data obtained also suggest that the interaction between the hormone and its target cell is not readily reversible and that only a certain proportion of target cells in a given population of lymphocytes can be activated by a constant and limited amount of thymus humoral factor.", "contents": "Effect of thymic humoral factor on intracellular levels of cyclic AMP in human peripheral blood lymphocytes. The exposure of human peripheral blood lymphocytes to thymus hormone causes an increase in the intracellular cyclic AMP level in these cells. Studies of the thymus-hormone-induced changes in cellular cyclic AMP levels revealed that cord blood lymphocytes contain significantly more target cells for the hormone than adult peripheral blood lymphocytes. The data obtained also suggest that the interaction between the hormone and its target cell is not readily reversible and that only a certain proportion of target cells in a given population of lymphocytes can be activated by a constant and limited amount of thymus humoral factor."}
{"id": "PMID:202580", "title": "[Hormones and hair growth in man].", "content": "A literature review tries to diminish the ambiguity between hormones and hairs. Therefore the hormonal action in general (regulation of the protein synthesis indirectly by enzymatical regulation of the AMP-system or directly by hormones as active metabolites) and the methods to explore hormones-hair-interaction are discussed. Hormones pertaining to the pituitary-adrenal-gonadal axis are regarded as the paramount hormones; therefore the results of research in testosterone, 5-alpha-dihydrotestosterone, estrogens, progesterone, glucocorticoids, the hypophysis and its tropins are recapitulated. The main disorders of hair-growth, pattern baldness and \"idiopathic\" hirsutism, which would be dependent on a similar disturbance of androgen metabolism, are discussed. Pathology in hair-growth may arise in any point of the cascade of hormone action.", "contents": "[Hormones and hair growth in man]. A literature review tries to diminish the ambiguity between hormones and hairs. Therefore the hormonal action in general (regulation of the protein synthesis indirectly by enzymatical regulation of the AMP-system or directly by hormones as active metabolites) and the methods to explore hormones-hair-interaction are discussed. Hormones pertaining to the pituitary-adrenal-gonadal axis are regarded as the paramount hormones; therefore the results of research in testosterone, 5-alpha-dihydrotestosterone, estrogens, progesterone, glucocorticoids, the hypophysis and its tropins are recapitulated. The main disorders of hair-growth, pattern baldness and \"idiopathic\" hirsutism, which would be dependent on a similar disturbance of androgen metabolism, are discussed. Pathology in hair-growth may arise in any point of the cascade of hormone action."}
{"id": "PMID:202582", "title": "Isolation of two new polymyxin group antibiotics. (Studies on antibiotics from the genus Bacillus. XX).", "content": "Two new members of polymyxin group antibiotics, polymyxins S1 and T1, were isolated from the culture broths of strains identified as Bacillus polymyxa Rs-6 and Bacillus polymyxa E-12, respectively. These antibiotics are strongly basic substances, their hydrochloric acid salts are soluble in water and methanol. They are primarily active against Gram-negative bacteria in vitro and in vivo though polymyxin T1 exhibits higher activities against Gram-positive bacteria than other polymyxin group antibiotics.", "contents": "Isolation of two new polymyxin group antibiotics. (Studies on antibiotics from the genus Bacillus. XX). Two new members of polymyxin group antibiotics, polymyxins S1 and T1, were isolated from the culture broths of strains identified as Bacillus polymyxa Rs-6 and Bacillus polymyxa E-12, respectively. These antibiotics are strongly basic substances, their hydrochloric acid salts are soluble in water and methanol. They are primarily active against Gram-negative bacteria in vitro and in vivo though polymyxin T1 exhibits higher activities against Gram-positive bacteria than other polymyxin group antibiotics."}
{"id": "PMID:202583", "title": "The structure of polymyxin S. (Studies on antibiotics from the genus Bacillus. XXI).", "content": "Amino acid analysis on the acid hydrolyzate of polymyxin S1 revealed its amino acid composition. Isolation of the constituent amino acids and measurement of their optical activities clarified their chiralities: Dab(5L), Thr(3L), Ser(1D) and Phe(1D). The constituent fatty acid was identified with anteisononanoic acid by gas chromatography and mass spectrometry. By the action of polymyxin acylase, deacyl polymyxin S was obtained. Successive EDMAN degradation reaction on deacyl polymyxin S revealed the amino acid sequence. Further evidence for the structure of polymyxin S1 was obtained by partial acid hydrolysis on tetra-(DNP)-polymyxin S1.", "contents": "The structure of polymyxin S. (Studies on antibiotics from the genus Bacillus. XXI). Amino acid analysis on the acid hydrolyzate of polymyxin S1 revealed its amino acid composition. Isolation of the constituent amino acids and measurement of their optical activities clarified their chiralities: Dab(5L), Thr(3L), Ser(1D) and Phe(1D). The constituent fatty acid was identified with anteisononanoic acid by gas chromatography and mass spectrometry. By the action of polymyxin acylase, deacyl polymyxin S was obtained. Successive EDMAN degradation reaction on deacyl polymyxin S revealed the amino acid sequence. Further evidence for the structure of polymyxin S1 was obtained by partial acid hydrolysis on tetra-(DNP)-polymyxin S1."}
{"id": "PMID:202584", "title": "The structure of polymyxin T1. (Studies on antibiotics from the genus Bacillus. XXII).", "content": "Amino acid analysis of the acid hydrolyzate of polymyxin T1 revealed the amino acid composition. Isolation of the constituent amino acids and measurement of their optical activities clarified their chiralities. These were 2,4-diaminobutyric acid (6L), Thr(1L), Leu(2L) and Phe(1D). The constituent fatty acid was identified as anteisononanoic acid by gas chromatography and mass spectrometry. Deacylation with polymyxin acylase afforded deacyl polymyxin T. Successive EDMAN degradation on deacyl polymyxin T revealed most of its amino acid sequence. The chemical cleavage reaction for fragmentation of threonyl peptide amino acid sequence. The chemical cleavage reaction for fragmentation of threonyl peptide on penta(DNP)-polymyxin T1 cleaved it at the C-terminal side of the Thr residue to afford a DNP-octapeptide, whose sequence was clarified by EDMAN degradation. Thus, the structure of polymyxin T1 was determined.", "contents": "The structure of polymyxin T1. (Studies on antibiotics from the genus Bacillus. XXII). Amino acid analysis of the acid hydrolyzate of polymyxin T1 revealed the amino acid composition. Isolation of the constituent amino acids and measurement of their optical activities clarified their chiralities. These were 2,4-diaminobutyric acid (6L), Thr(1L), Leu(2L) and Phe(1D). The constituent fatty acid was identified as anteisononanoic acid by gas chromatography and mass spectrometry. Deacylation with polymyxin acylase afforded deacyl polymyxin T. Successive EDMAN degradation on deacyl polymyxin T revealed most of its amino acid sequence. The chemical cleavage reaction for fragmentation of threonyl peptide amino acid sequence. The chemical cleavage reaction for fragmentation of threonyl peptide on penta(DNP)-polymyxin T1 cleaved it at the C-terminal side of the Thr residue to afford a DNP-octapeptide, whose sequence was clarified by EDMAN degradation. Thus, the structure of polymyxin T1 was determined."}
{"id": "PMID:202585", "title": "Disruption of the Escherichia coli outer membrane permeability barrier by immobilized polymyxin B.", "content": "One of the apparent roles of the outer membrane system in gram-negative bacteria is to function as a selective permeability barrier. A number of antibiotics active against gram-positive bacteria are relatively ineffective against gram-negative bacteria presumably because of the implied barrier function of the outer membrane. This interpretation has been strengthened by studies demonstrating synergism between outer membrane perturbing agents such as EDTA or polymyxin B and specific antibiotics. In the case of polymyxin B, it is not totally clear that synergism with other antimicrobials is due to disruption of the outer membrane permeability barrier or to interactions with the inner membrane. In order to resolve this question, polymyxin B was covalently attached to agarose in order to limit interactions with the outer surface of E. coli. These studies demonstrate that immobilized polymyxin B acts synergistically with bacitracin, rifampicin, or lysozyme. It is proposed that synergistic effects exhibited by polymyxin B are due to its interaction with the outer membrane system.", "contents": "Disruption of the Escherichia coli outer membrane permeability barrier by immobilized polymyxin B. One of the apparent roles of the outer membrane system in gram-negative bacteria is to function as a selective permeability barrier. A number of antibiotics active against gram-positive bacteria are relatively ineffective against gram-negative bacteria presumably because of the implied barrier function of the outer membrane. This interpretation has been strengthened by studies demonstrating synergism between outer membrane perturbing agents such as EDTA or polymyxin B and specific antibiotics. In the case of polymyxin B, it is not totally clear that synergism with other antimicrobials is due to disruption of the outer membrane permeability barrier or to interactions with the inner membrane. In order to resolve this question, polymyxin B was covalently attached to agarose in order to limit interactions with the outer surface of E. coli. These studies demonstrate that immobilized polymyxin B acts synergistically with bacitracin, rifampicin, or lysozyme. It is proposed that synergistic effects exhibited by polymyxin B are due to its interaction with the outer membrane system."}
{"id": "PMID:202588", "title": "Electron spin resonance studies on the lipoxygenase reaction by spin trapping and spin labelling methods.", "content": "The rate of oxygenation and that of trapping linoleic acid free radicals in the lipoxygenase [EC 1.13.11.12] reaction were measured in the presence of linoleic acid, oxygen, and nitrosobenzene at various concentrations, with a Clark oxygen electrode and ESR spectroscopy. The results were interpreted under the assumption that the free radical of linoleic acid, an intermediate of the lipoxygenase reaction, reacts competitively with oxygen or nitrosobenzene. The oxidation of the iron in the active site of lipoxygenase caused by the spin label reagent, 2-(10-carboxydecyl)-2-hexyl-4,4-dimethyl-3-oxazolidinyloxyl, was also observed by ESR- and fluorescence-spectroscopy.", "contents": "Electron spin resonance studies on the lipoxygenase reaction by spin trapping and spin labelling methods. The rate of oxygenation and that of trapping linoleic acid free radicals in the lipoxygenase [EC 1.13.11.12] reaction were measured in the presence of linoleic acid, oxygen, and nitrosobenzene at various concentrations, with a Clark oxygen electrode and ESR spectroscopy. The results were interpreted under the assumption that the free radical of linoleic acid, an intermediate of the lipoxygenase reaction, reacts competitively with oxygen or nitrosobenzene. The oxidation of the iron in the active site of lipoxygenase caused by the spin label reagent, 2-(10-carboxydecyl)-2-hexyl-4,4-dimethyl-3-oxazolidinyloxyl, was also observed by ESR- and fluorescence-spectroscopy."}
{"id": "PMID:202589", "title": "Energy transduction and adenine nucleotides in mitochondria from rat liver after hypoxic perfusion.", "content": "The characteristics of mitochondria isolated from perfused livers of rats under hypoxic or oxic conditions were studied. The electron transfer activity was about 60% of normal after hypoxic perfusion for 3 h, but respiratory control was abolished almost completely. These parameters recovered considerably on subsequent oxic perfusion. The adenine nucleotide contents and their net uptake decreased in hypoxia, closely correlated with the energy transduction. Energy-dependent nicotinamide nucleotide transhydrogenase activity and NAD reduction by succinate in submitochondrial particles were most severely inhibited after hypoxic perfusion and were also correlated with adenine nucleotide contents in the particles. These results are discussed in terms of the involvement of adenine nucleotides in energy-transducing systems in mitochondrial membranes.", "contents": "Energy transduction and adenine nucleotides in mitochondria from rat liver after hypoxic perfusion. The characteristics of mitochondria isolated from perfused livers of rats under hypoxic or oxic conditions were studied. The electron transfer activity was about 60% of normal after hypoxic perfusion for 3 h, but respiratory control was abolished almost completely. These parameters recovered considerably on subsequent oxic perfusion. The adenine nucleotide contents and their net uptake decreased in hypoxia, closely correlated with the energy transduction. Energy-dependent nicotinamide nucleotide transhydrogenase activity and NAD reduction by succinate in submitochondrial particles were most severely inhibited after hypoxic perfusion and were also correlated with adenine nucleotide contents in the particles. These results are discussed in terms of the involvement of adenine nucleotides in energy-transducing systems in mitochondrial membranes."}
{"id": "PMID:202590", "title": "Studies on nitrate reductase of Clostridium perfringens. Purification, some properties, and effect of tungstate on its formation.", "content": "Nitrate reductase (NaR) linked to reduced methyl viologen from Clostridium perfringens was purified by ammonium sulfate precipitation. DEAE-cellulose chromatography, disc electrophoresis on polyacrylamide gel, and triple DEAE-Sephadex chromatography. The specific activity was increased 1,200-fold with a yield of 9%. The purified preparation was nearly homogeneous in disc electrophoresis. It was brown, and its spectrum showed a slight shoulder near 420 nm as well as a peak at 280 nm. The molecular weight was found to be 90,000 based on s020,w (5.8S) and 80,000 by Sephadex G-100 gel filtration. In SDS-polyacrylamide electrophoresis, it showed only a single band with a molecular weight of 90,000; it had no subunit structure. The isoelectric point was pH 5.5, and the optimum pH was 9. Mn2+, Fe2+, Mg2+, and Ca2+ stimulated the activity. Km for nitrate was 0.10 mM, and nitrate was stoichiometrically reduced to nitrite in the presence of 2 mM Mn2+. Ferredoxin fraction obtained from extracts of the bacterium was utilizable as an electron donor at pH 8. Cyanide and azide inhibited the enzyme. The formation of NaR was induced by nitrate and inhibited by 0.5 mM tungstate, but recovered in the presence of 0.1 mM molybdate; NaR of C. perfringens appears to be a molybdo-iron-sulfur protein.", "contents": "Studies on nitrate reductase of Clostridium perfringens. Purification, some properties, and effect of tungstate on its formation. Nitrate reductase (NaR) linked to reduced methyl viologen from Clostridium perfringens was purified by ammonium sulfate precipitation. DEAE-cellulose chromatography, disc electrophoresis on polyacrylamide gel, and triple DEAE-Sephadex chromatography. The specific activity was increased 1,200-fold with a yield of 9%. The purified preparation was nearly homogeneous in disc electrophoresis. It was brown, and its spectrum showed a slight shoulder near 420 nm as well as a peak at 280 nm. The molecular weight was found to be 90,000 based on s020,w (5.8S) and 80,000 by Sephadex G-100 gel filtration. In SDS-polyacrylamide electrophoresis, it showed only a single band with a molecular weight of 90,000; it had no subunit structure. The isoelectric point was pH 5.5, and the optimum pH was 9. Mn2+, Fe2+, Mg2+, and Ca2+ stimulated the activity. Km for nitrate was 0.10 mM, and nitrate was stoichiometrically reduced to nitrite in the presence of 2 mM Mn2+. Ferredoxin fraction obtained from extracts of the bacterium was utilizable as an electron donor at pH 8. Cyanide and azide inhibited the enzyme. The formation of NaR was induced by nitrate and inhibited by 0.5 mM tungstate, but recovered in the presence of 0.1 mM molybdate; NaR of C. perfringens appears to be a molybdo-iron-sulfur protein."}
{"id": "PMID:202591", "title": "GLC analysis of the hydroxy and oxo compounds produced by the Smith degradation of reducing Di- and trisaccharides.", "content": "Reducing di- and trisaccharides were oxidized with periodate under conditions minimizing overoxidation, and the hydroxy and oxo compounds produced by subsequent reduction and hydrolysis were analyzed by GLC after trimethylsilylation. The present study has demonstrated that GLC analysis of the hydroxy and oxo compounds produced by Smith degradation is useful for linkage analysis of reducing di- and trisaccharides. In addition, it is suggested that the rate of periodate oxidation of the internal hexopyranose residue of trisaccharides depends markedly upon their structures.", "contents": "GLC analysis of the hydroxy and oxo compounds produced by the Smith degradation of reducing Di- and trisaccharides. Reducing di- and trisaccharides were oxidized with periodate under conditions minimizing overoxidation, and the hydroxy and oxo compounds produced by subsequent reduction and hydrolysis were analyzed by GLC after trimethylsilylation. The present study has demonstrated that GLC analysis of the hydroxy and oxo compounds produced by Smith degradation is useful for linkage analysis of reducing di- and trisaccharides. In addition, it is suggested that the rate of periodate oxidation of the internal hexopyranose residue of trisaccharides depends markedly upon their structures."}
{"id": "PMID:202598", "title": "Mechanism of the reaction catalyzed by carbamyl phosphate synthetase. Binding of ATP to the two functionally different ATP sites.", "content": "Application of the pulse-chase procedure to study of the binding and utilization of ATP by glutamine-dependent carbamyl phosphate synthetase from Escherichia coli showed that the enzyme binds the two molecules of ATP used in this reaction at the same time, and that the two ATP-binding sites are functionally different. Thus, ATP bound to the first ATP site is used for carboxy phosphate formation, and ATP bound to the second ATP site is used for phosphorylation of carbamate. The present and previous findings support a mechanism that involves intermediate formation of two highly unstable intermediates: carboxy phosphate and carbamate. It is proposed that the presence of all of the reactants on the enzyme at the start of the catalytic cycle allows immediate utilization of these labile compounds in the carbamyl phosphate synthesis reaction.", "contents": "Mechanism of the reaction catalyzed by carbamyl phosphate synthetase. Binding of ATP to the two functionally different ATP sites. Application of the pulse-chase procedure to study of the binding and utilization of ATP by glutamine-dependent carbamyl phosphate synthetase from Escherichia coli showed that the enzyme binds the two molecules of ATP used in this reaction at the same time, and that the two ATP-binding sites are functionally different. Thus, ATP bound to the first ATP site is used for carboxy phosphate formation, and ATP bound to the second ATP site is used for phosphorylation of carbamate. The present and previous findings support a mechanism that involves intermediate formation of two highly unstable intermediates: carboxy phosphate and carbamate. It is proposed that the presence of all of the reactants on the enzyme at the start of the catalytic cycle allows immediate utilization of these labile compounds in the carbamyl phosphate synthesis reaction."}
{"id": "PMID:202602", "title": "The selection of a stable rat hepatoma variant with concomitant increase in ploidy and permeability to glycerol.", "content": "By repeated selection for longer survival in an isotonic solution of glycerol, a stable subline of Novikoff rat hepatoma cells has been isolated. The cells exhibit markedly increased resistances to osmotic lysis  in isotonic solutions of glycerol. They are twice as large and have twice as many chromosomes as cells of the parental line. It is suggested that the osmotic stress procedure can be extended for the selection of numerous kinds of mutants and can be used as a method of analysis of membrane properties.", "contents": "The selection of a stable rat hepatoma variant with concomitant increase in ploidy and permeability to glycerol. By repeated selection for longer survival in an isotonic solution of glycerol, a stable subline of Novikoff rat hepatoma cells has been isolated. The cells exhibit markedly increased resistances to osmotic lysis  in isotonic solutions of glycerol. They are twice as large and have twice as many chromosomes as cells of the parental line. It is suggested that the osmotic stress procedure can be extended for the selection of numerous kinds of mutants and can be used as a method of analysis of membrane properties."}
{"id": "PMID:202603", "title": "The role of adenosine 3',5'-cyclic monophosphate in the density-dependent regulation of growth and tyrosinase activity of B-16 melanoma cells.", "content": "Incubation of cultured B-16 melanoma cells with 1-methyl-3-isobutyl xanthine (MIX) produced a sustained rise in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) which preceded an increase in the specific activity of tyrosinase (EC 1.10.3.1). Cultures of two clones of melanoma cells, one having a mean population doubling time twice that of the other, showed density-dependent inhibition of growth. The tyrosinase activity of each line increased progressively during logarithmic growth, reaching maximal values shortly after the cultures achieved confluence. Intracellular cAMP levels fell during logarithmic growth, being minimal in confluent cultures. The stimulatory effects of MIX and confluence on tyrosinase activity were additive. Cells plated at high density had a lower tyrosinase activity than cells allowed to achieve a similar density by successive division from sparsely planted cultures although the intracellular cAMP levels of such cultures were not different. We support the observations of other investigators that agents which increase intracellular cAMP concentrations can both inhibit cell division and stimulate tyrosinase activity. There are, however, mechanisms for increasing tyrosinase activity and inhibiting cell division which are expressed as B-16 melanoma cells approach confluence and which are not mediated by an increase in intracellular cAMP concentrations.", "contents": "The role of adenosine 3',5'-cyclic monophosphate in the density-dependent regulation of growth and tyrosinase activity of B-16 melanoma cells. Incubation of cultured B-16 melanoma cells with 1-methyl-3-isobutyl xanthine (MIX) produced a sustained rise in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) which preceded an increase in the specific activity of tyrosinase (EC 1.10.3.1). Cultures of two clones of melanoma cells, one having a mean population doubling time twice that of the other, showed density-dependent inhibition of growth. The tyrosinase activity of each line increased progressively during logarithmic growth, reaching maximal values shortly after the cultures achieved confluence. Intracellular cAMP levels fell during logarithmic growth, being minimal in confluent cultures. The stimulatory effects of MIX and confluence on tyrosinase activity were additive. Cells plated at high density had a lower tyrosinase activity than cells allowed to achieve a similar density by successive division from sparsely planted cultures although the intracellular cAMP levels of such cultures were not different. We support the observations of other investigators that agents which increase intracellular cAMP concentrations can both inhibit cell division and stimulate tyrosinase activity. There are, however, mechanisms for increasing tyrosinase activity and inhibiting cell division which are expressed as B-16 melanoma cells approach confluence and which are not mediated by an increase in intracellular cAMP concentrations."}
{"id": "PMID:202604", "title": "Increased membrane transport of 2-deoxyglucose and 3-O-methylglucose is an early event in the transformation of chick embryo fibroblasts by Rous sarcoma virus.", "content": "Transformation of chicken embryo fibroblasts with Rous sarcoma virus results in cells with an enhanced rate of hexose uptake. We have examined transport of the glucose analogs 2-deoxyglucose and 3-O-methylglucose in cells infected with a temperature sensitive variant of the virus. In cells shifted from restrictive to permissive conditions for transformation, increased transport of the non-phosphorylatable analog 3-O-methylglucose occurs at the same time as that of 2-deoxyglucose, a phosphorylatable analog. This enhanced rate of transport can be observed within three hours of the temperature shift. There is a corresponding decrease in the transport rate of both analogs following shift to the restrictive temperature. These results suggest that increased transport is likely to be the primary event in causing transformation-specific changes in sugar metabolism. We have also examined uptake into the internal pools of both the phosphorylated and non-phosphorylated forms of 2-deoxyglucose in normal cells and in cells transformed by the wild-type virus. These data indicate a corresponding increase in the rate of accumulation of the free sugar in transformed cells and point to transport as the rate limiting step in the accumulation of 2-deoxyglucose in both normal and transformed chicken embryo cells.", "contents": "Increased membrane transport of 2-deoxyglucose and 3-O-methylglucose is an early event in the transformation of chick embryo fibroblasts by Rous sarcoma virus. Transformation of chicken embryo fibroblasts with Rous sarcoma virus results in cells with an enhanced rate of hexose uptake. We have examined transport of the glucose analogs 2-deoxyglucose and 3-O-methylglucose in cells infected with a temperature sensitive variant of the virus. In cells shifted from restrictive to permissive conditions for transformation, increased transport of the non-phosphorylatable analog 3-O-methylglucose occurs at the same time as that of 2-deoxyglucose, a phosphorylatable analog. This enhanced rate of transport can be observed within three hours of the temperature shift. There is a corresponding decrease in the transport rate of both analogs following shift to the restrictive temperature. These results suggest that increased transport is likely to be the primary event in causing transformation-specific changes in sugar metabolism. We have also examined uptake into the internal pools of both the phosphorylated and non-phosphorylated forms of 2-deoxyglucose in normal cells and in cells transformed by the wild-type virus. These data indicate a corresponding increase in the rate of accumulation of the free sugar in transformed cells and point to transport as the rate limiting step in the accumulation of 2-deoxyglucose in both normal and transformed chicken embryo cells."}
{"id": "PMID:202606", "title": "A fluorescence enhancement assay of cell fusion.", "content": "Two probes were synthesized which consist of fluorescent molecules conjugated to saturated hydrocarbon chains, 18 carbons long, to ensure their localization into cellular membranes. There is an overlap between the emission spectrum of one probe (donor) and the absorption spectrum of the other probe (acceptor). By the use of appropriate wavelengths it is possible to specifically excite the donor probe and record the fluorescence of the acceptor probe. Two cell populations, each labelled with one of the probes, were infected with a virus that causes cell fusion, mixed in equal proportions, and the fluorescence of the acceptor probe measured as a function of time after infection. An increase in fluorescence was observed beginning at the time of onset of cell fusion indicating a mixing of the fluorescent membrane molecules. An investigation of the distance dependence indicated that the increase in fluorescence was mainly due to resonance energy transfer and not to photon emission and reabsorption. Resonance energy transfer requires that the 2 probes be close together and that there be an overlap of the emission spectrum of the donor probe and the absorption spectrum of the acceptor probe. The possible application of this assay to other types of membrane fusion is noted.", "contents": "A fluorescence enhancement assay of cell fusion. Two probes were synthesized which consist of fluorescent molecules conjugated to saturated hydrocarbon chains, 18 carbons long, to ensure their localization into cellular membranes. There is an overlap between the emission spectrum of one probe (donor) and the absorption spectrum of the other probe (acceptor). By the use of appropriate wavelengths it is possible to specifically excite the donor probe and record the fluorescence of the acceptor probe. Two cell populations, each labelled with one of the probes, were infected with a virus that causes cell fusion, mixed in equal proportions, and the fluorescence of the acceptor probe measured as a function of time after infection. An increase in fluorescence was observed beginning at the time of onset of cell fusion indicating a mixing of the fluorescent membrane molecules. An investigation of the distance dependence indicated that the increase in fluorescence was mainly due to resonance energy transfer and not to photon emission and reabsorption. Resonance energy transfer requires that the 2 probes be close together and that there be an overlap of the emission spectrum of the donor probe and the absorption spectrum of the acceptor probe. The possible application of this assay to other types of membrane fusion is noted."}
{"id": "PMID:202608", "title": "Endotoxin-induced platelet aggregation and secretion. I. Morphological changes and pharmacological effects.", "content": "Endotoxin lipopolysaccharide (LPS) from Acinetobacter 199A induced aggregation of blood platelets from immune adherence-positive species (rat, rabbit) but not from immune adherence-negative species such as pig and man. Aggregation occurred in 2 phases: the first was not accompanied by secretion of platelet constituents, was apparently a consequence of C3 activation, and was selectively inhibited by EGTA. The second phase of aggregation was associated with secretion of platelet granule contents, and with a lesser amount of cytoplasmic leakage. Secondary aggregation was abolished by the sulphydryl alkylating agent N-ethylmaleimide, and by agents which increased the level of cyclic AMP in platelets, such as prostaglandin E1 (a stimulator of adenylate cyclase) and methyl xanthines (inhibitors of phosphodiesterase). Secondary aggregation was partly inhibited by agents which block platelet prostaglandin biosynthesis (e.g. aspirin, indomethacin). Primary aggregation was unaffected by these inhibitors at concentrations which blocked secondary aggregation.", "contents": "Endotoxin-induced platelet aggregation and secretion. I. Morphological changes and pharmacological effects. Endotoxin lipopolysaccharide (LPS) from Acinetobacter 199A induced aggregation of blood platelets from immune adherence-positive species (rat, rabbit) but not from immune adherence-negative species such as pig and man. Aggregation occurred in 2 phases: the first was not accompanied by secretion of platelet constituents, was apparently a consequence of C3 activation, and was selectively inhibited by EGTA. The second phase of aggregation was associated with secretion of platelet granule contents, and with a lesser amount of cytoplasmic leakage. Secondary aggregation was abolished by the sulphydryl alkylating agent N-ethylmaleimide, and by agents which increased the level of cyclic AMP in platelets, such as prostaglandin E1 (a stimulator of adenylate cyclase) and methyl xanthines (inhibitors of phosphodiesterase). Secondary aggregation was partly inhibited by agents which block platelet prostaglandin biosynthesis (e.g. aspirin, indomethacin). Primary aggregation was unaffected by these inhibitors at concentrations which blocked secondary aggregation."}
{"id": "PMID:202609", "title": "Isoelectric focusing of viral polypeptides in urea. A methodological study on poliovirus.", "content": "The applicability of isoelectric focusing in urea to the analysis of viral polypeptides is reported, using poliovirus as a model. Experimental techniques for the dissociation of virus particles, for isoelectric focusing in urea-containing polyacrylamide gels (rods, flat bed and slab gels) and for pH measurement and two-dimensional analysis are described and their results, as applied to poliovirus polypeptides, discussed. Special attention is given to problems of recovery of all of the proteins and the incidence of artifacts. The influence of reagents, dissociation conditions, focusing procedures and preparation and storage of virus material on the occurrence of charge modifications of the polypeptides has been investigated. Some recommendations are made for the application of the method to other viruses of particles.", "contents": "Isoelectric focusing of viral polypeptides in urea. A methodological study on poliovirus. The applicability of isoelectric focusing in urea to the analysis of viral polypeptides is reported, using poliovirus as a model. Experimental techniques for the dissociation of virus particles, for isoelectric focusing in urea-containing polyacrylamide gels (rods, flat bed and slab gels) and for pH measurement and two-dimensional analysis are described and their results, as applied to poliovirus polypeptides, discussed. Special attention is given to problems of recovery of all of the proteins and the incidence of artifacts. The influence of reagents, dissociation conditions, focusing procedures and preparation and storage of virus material on the occurrence of charge modifications of the polypeptides has been investigated. Some recommendations are made for the application of the method to other viruses of particles."}
{"id": "PMID:202610", "title": "Interaction of polymorphonuclear neutrophils with Escherichia coli. Effect of enterotoxin on phagocytosis, killing, chemotaxis, and cyclic AMP.", "content": "Enterotoxigenic Escherichia coli are associated with noninflammatory diarrhea and stimulate adenylate cyclase activity of mammalian cells, thereby increasing intracellular cyclic adenosine 3',5'-monophosphate (cyclic AMP). Increased concentrations of cyclic AMP in polymorphonuclear neutrophils (PMN) inhibit phagocytosis, candidacidal activity, granule discharge, and chemotactic responsiveness. We examined the effect of enterotoxin on the interaction of human PMN with E. coli. Enterotoxigenic and nonenterotoxigenic strains, including serotypes of E. coli identical except for the presence or absence of the plasmid coding for enterotoxin production, were utilized. Enterotoxigenic and nonenterotoxigenic E. coli, tumbled with PMN, were phagocytized and killed (>97%) equally well, and these strains stimulated PMN hexose monophosphate shunt activity equivalently.However, a chemotaxis assay under agarose demonstrated that filtrates of 10 enterotoxigenic strains were less chemotactic for PMN by 15+/-2% total migration or 46+/-1% directed migration, when compared with 6 non-enterotoxigenic strains (P < 0.001). Inactivation of the enterotoxin by heat (65 degrees C for 30 min) or antibodies formed to E. coli enterotoxin eliminated the inhibitory effect of the enterotoxic filtrates for PMN chemotaxis. Addition of purified E. coli enterotoxin directly to the PMN decreased chemotaxis to E. coli filtrates by 32+/-2% (P < 0.001). These data suggest that the effect was due to the heat-labile enterotoxin. The phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (0.1 mM), which potentiates effects due to an increase in intracellular cyclic AMP, further decreased total PMN migration (random plus directed) toward enterotoxic filtrates to 46% of that to nonenterotoxic filtrates (P < 0.001). Addition of cholera toxin (1 mug/ml), which is similar to E. coli enterotoxin, to the PMN inhibited total migration toward nonenterotoxic filtrates by 16+/-2% (P < 0.001). Exogenous dibutyryl cyclic AMP (2 mM) inhibited total PMN migration toward E. coli filtrates by 32% (P < 0.001). PMN intracellular cyclic AMP levels increased by 220% after 2 h of incubation with purified E. coli enterotoxin. The decreased chemotactic attractiveness of enterotoxic E. coli filtrates appears to be related to the ability of enterotoxin to increase cyclic AMP in PMN. Enterotoxin production by E. coli may be advantageous to the microbe by decreasing its chemotactic appeal for PMN.", "contents": "Interaction of polymorphonuclear neutrophils with Escherichia coli. Effect of enterotoxin on phagocytosis, killing, chemotaxis, and cyclic AMP. Enterotoxigenic Escherichia coli are associated with noninflammatory diarrhea and stimulate adenylate cyclase activity of mammalian cells, thereby increasing intracellular cyclic adenosine 3',5'-monophosphate (cyclic AMP). Increased concentrations of cyclic AMP in polymorphonuclear neutrophils (PMN) inhibit phagocytosis, candidacidal activity, granule discharge, and chemotactic responsiveness. We examined the effect of enterotoxin on the interaction of human PMN with E. coli. Enterotoxigenic and nonenterotoxigenic strains, including serotypes of E. coli identical except for the presence or absence of the plasmid coding for enterotoxin production, were utilized. Enterotoxigenic and nonenterotoxigenic E. coli, tumbled with PMN, were phagocytized and killed (>97%) equally well, and these strains stimulated PMN hexose monophosphate shunt activity equivalently.However, a chemotaxis assay under agarose demonstrated that filtrates of 10 enterotoxigenic strains were less chemotactic for PMN by 15+/-2% total migration or 46+/-1% directed migration, when compared with 6 non-enterotoxigenic strains (P < 0.001). Inactivation of the enterotoxin by heat (65 degrees C for 30 min) or antibodies formed to E. coli enterotoxin eliminated the inhibitory effect of the enterotoxic filtrates for PMN chemotaxis. Addition of purified E. coli enterotoxin directly to the PMN decreased chemotaxis to E. coli filtrates by 32+/-2% (P < 0.001). These data suggest that the effect was due to the heat-labile enterotoxin. The phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (0.1 mM), which potentiates effects due to an increase in intracellular cyclic AMP, further decreased total PMN migration (random plus directed) toward enterotoxic filtrates to 46% of that to nonenterotoxic filtrates (P < 0.001). Addition of cholera toxin (1 mug/ml), which is similar to E. coli enterotoxin, to the PMN inhibited total migration toward nonenterotoxic filtrates by 16+/-2% (P < 0.001). Exogenous dibutyryl cyclic AMP (2 mM) inhibited total PMN migration toward E. coli filtrates by 32% (P < 0.001). PMN intracellular cyclic AMP levels increased by 220% after 2 h of incubation with purified E. coli enterotoxin. The decreased chemotactic attractiveness of enterotoxic E. coli filtrates appears to be related to the ability of enterotoxin to increase cyclic AMP in PMN. Enterotoxin production by E. coli may be advantageous to the microbe by decreasing its chemotactic appeal for PMN."}
{"id": "PMID:202611", "title": "Protein degradation in normal and beige (Chediak-Higashi) mice,.", "content": "The beige mouse, C57BL/6 (bg/bg), is an animal model for the Chediak-Higashi syndrome in man, a disease characterized morphologically by giant lysosomes in most cell types. Half-lives for the turnover of [(14)C]bicarbonate-labeled total soluble liver protein were determined in normal and beige mice. No significant differences were observed between the normal and mutant strain for both rapidly and slowly turning-over classes of proteins. Glucagon treatment during the time-course of protein degradation had similar effects on both normal and mutant strains and led to the conclusion that the rate of turnover of endogenous intracellular protein in the beige mouse liver does not differ from normal. The rates of uptake and degradation of an exogenous protein were determined in normal and beige mice by intravenously injecting (125)I-bovine serum albumin and following, in peripheral blood, the loss with time of phosphotungstic acid-insoluble bovine serum albumin and the parallel appearance of phosphotungstic acid-soluble (degraded) material. No significant differences were observed between beige and normal mice in the uptake by liver lysosomes of (125)I-bovine serum albumin (t((1/2)) = 3.9 and 2.8 h, respectively). However, it was found that lysosomes from livers of beige mice released phosphotungstic acid-soluble radioactivity at a rate significantly slower than normal (t((1/2)) = 6.8 and 3.1 h, respectively). This defect in beige mice could be corrected by chronic administration of carbamyl choline (t((1/2)) = 3.5 h), a cholinergic agonist which raises intracellular cyclic GMP levels. However, no significant differences between normal and beige mice were observed either in the ability of soluble extracts of liver and kidney to bind [(3)H]cyclic GMP in vitro or in the basal levels of cyclic AMP in both tissues. The relevance of these observations to the presumed biochemical defect underlying the Chediak-Higashi syndrome is discussed.", "contents": "Protein degradation in normal and beige (Chediak-Higashi) mice,. The beige mouse, C57BL/6 (bg/bg), is an animal model for the Chediak-Higashi syndrome in man, a disease characterized morphologically by giant lysosomes in most cell types. Half-lives for the turnover of [(14)C]bicarbonate-labeled total soluble liver protein were determined in normal and beige mice. No significant differences were observed between the normal and mutant strain for both rapidly and slowly turning-over classes of proteins. Glucagon treatment during the time-course of protein degradation had similar effects on both normal and mutant strains and led to the conclusion that the rate of turnover of endogenous intracellular protein in the beige mouse liver does not differ from normal. The rates of uptake and degradation of an exogenous protein were determined in normal and beige mice by intravenously injecting (125)I-bovine serum albumin and following, in peripheral blood, the loss with time of phosphotungstic acid-insoluble bovine serum albumin and the parallel appearance of phosphotungstic acid-soluble (degraded) material. No significant differences were observed between beige and normal mice in the uptake by liver lysosomes of (125)I-bovine serum albumin (t((1/2)) = 3.9 and 2.8 h, respectively). However, it was found that lysosomes from livers of beige mice released phosphotungstic acid-soluble radioactivity at a rate significantly slower than normal (t((1/2)) = 6.8 and 3.1 h, respectively). This defect in beige mice could be corrected by chronic administration of carbamyl choline (t((1/2)) = 3.5 h), a cholinergic agonist which raises intracellular cyclic GMP levels. However, no significant differences between normal and beige mice were observed either in the ability of soluble extracts of liver and kidney to bind [(3)H]cyclic GMP in vitro or in the basal levels of cyclic AMP in both tissues. The relevance of these observations to the presumed biochemical defect underlying the Chediak-Higashi syndrome is discussed."}
{"id": "PMID:202612", "title": "Control of 3-hydroxy-3-methylglutaryl-CoA reductase activity in cultured human fibroblasts by very low density lipoproteins of subjects with hypertriglyceridemia.", "content": "Very low density lipoproteins (VLDL) and low density lipoproteins (LDL) from human normolipemic plasma, and the VLDL, the intermediate density lipoprotein (IDL), and LDL from patients with Type III hyperlipoproteinemic plasma were tested for their abilities to suppress the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in cultured human fibroblasts from normal subjects and a Type III patient. Regulation of cholesterol synthesis in the fibroblasts of a patient with Type III hyperlipoproteinemia appears to be normal. VLDL from normal subjects, isolated by angle head ultracentrifugation (d < 1.006) or by gel filtration on BioGel A-5m, were about 5 times less effective than LDL in suppressing HMG-CoA reductase activity, based on protein content, in agreement with previous reports with normal fibroblasts. Zonal centrifugation of normal VLDL isolated by both methods showed that the VLDL contained IDL. Normal VLDL from the angle head rotor, refractionated by the zonal method, had little, if any, ability to suppress the HMG-CoA reductase activity in either normal or Type III fibroblasts. VLDL, IDL, and LDL fractionated by zonal ultracentrifugation from Type III plasma gave half-maximum inhibition at 0.2-0.5 mug of protein/ml, indistinguishable from the suppression caused by normal LDL. Type III VLDL did not suppress HMG-CoA reductase in mutant LDL receptor-negative fibroblasts. Zonally isolated VLDL obtained from one Type IV and one Type V patient gave half-maximal suppression at 5 and 0.5 mug of protein/ml, respectively. Molecular diameters and apoprotein compositions of the zonally isolated normal and Type III VLDL were similar; the major difference in composition was that Type III VLDL contained more cholesteryl esters and less triglyceride than did normal VLDL. The compositions and diameters of the Type IV and Type V VLDL were similar to normal VLDL. These findings show that the basic defect in Type III hyperlipoproteinemia is qualitatively different from the cellular defect found in familial hypercholesterolemia, since the regulation of HMG-CoA reductase activity is normal in Type III fibroblasts. The metabolic defect in hypertriglyceridemia is related to the triglyceriderich lipoproteins which, free of other lipoproteins, have an enhanced ability to interact with cultured fibroblasts to regulate HMG-CoA reductase activity. These studies suggest that, in hypertriglyceridemia, there is a mechanism for direct cellular catabolism of VLDL which is not functional for normal VLDL.", "contents": "Control of 3-hydroxy-3-methylglutaryl-CoA reductase activity in cultured human fibroblasts by very low density lipoproteins of subjects with hypertriglyceridemia. Very low density lipoproteins (VLDL) and low density lipoproteins (LDL) from human normolipemic plasma, and the VLDL, the intermediate density lipoprotein (IDL), and LDL from patients with Type III hyperlipoproteinemic plasma were tested for their abilities to suppress the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in cultured human fibroblasts from normal subjects and a Type III patient. Regulation of cholesterol synthesis in the fibroblasts of a patient with Type III hyperlipoproteinemia appears to be normal. VLDL from normal subjects, isolated by angle head ultracentrifugation (d < 1.006) or by gel filtration on BioGel A-5m, were about 5 times less effective than LDL in suppressing HMG-CoA reductase activity, based on protein content, in agreement with previous reports with normal fibroblasts. Zonal centrifugation of normal VLDL isolated by both methods showed that the VLDL contained IDL. Normal VLDL from the angle head rotor, refractionated by the zonal method, had little, if any, ability to suppress the HMG-CoA reductase activity in either normal or Type III fibroblasts. VLDL, IDL, and LDL fractionated by zonal ultracentrifugation from Type III plasma gave half-maximum inhibition at 0.2-0.5 mug of protein/ml, indistinguishable from the suppression caused by normal LDL. Type III VLDL did not suppress HMG-CoA reductase in mutant LDL receptor-negative fibroblasts. Zonally isolated VLDL obtained from one Type IV and one Type V patient gave half-maximal suppression at 5 and 0.5 mug of protein/ml, respectively. Molecular diameters and apoprotein compositions of the zonally isolated normal and Type III VLDL were similar; the major difference in composition was that Type III VLDL contained more cholesteryl esters and less triglyceride than did normal VLDL. The compositions and diameters of the Type IV and Type V VLDL were similar to normal VLDL. These findings show that the basic defect in Type III hyperlipoproteinemia is qualitatively different from the cellular defect found in familial hypercholesterolemia, since the regulation of HMG-CoA reductase activity is normal in Type III fibroblasts. The metabolic defect in hypertriglyceridemia is related to the triglyceriderich lipoproteins which, free of other lipoproteins, have an enhanced ability to interact with cultured fibroblasts to regulate HMG-CoA reductase activity. These studies suggest that, in hypertriglyceridemia, there is a mechanism for direct cellular catabolism of VLDL which is not functional for normal VLDL."}
{"id": "PMID:202613", "title": "Developmental aspects of the pituitary-adrenal axis response to hemorrhagic stress in lamb fetuses in utero.", "content": "Plasma ACTH and corticosteroid concentrations were measured by radioimmunoassay in chronically catheterized fetuses of 32 pregnant sheep. Fetal plasma ACTH levels 38+/-5 pg/ml (means+/-SEM) were slightly (P < 0.05) lower than maternal 54+/-4 pg/ml levels. No general rise in fetal plasma ACTH concentration was noted before 140 days gestation; however, fetal plasma corticoid levels began to increase after about 125 days. This suggested that an increase in fetal adrenal responsiveness to endogenous ACTH occurred during gestation. Hemorrhage of 15% of estimated blood volume decreased mean arterial pressure from 54+/-3 to 36+/-3 torr and increased plasma ACTH from 30+/-5 to 130+/-30 pg/ml in fetuses older than 0.80 gestation. In fetuses younger than 0.67 gestation, 15% hemorrhage caused no change in plasma ACTH levels despite a significant fall in mean arterial pressure. This suggests that system(s) subserving the ACTH response to mild hemorrhage are either absent or nonfunctional in the younger fetuses. The hemorrhage-induced increase in plasma ACTH levels was associated with a small rise in plasma corticoids in fetuses younger than 0.94 gestation. In older fetuses, a similar increase in plasma ACTH was associated with a pronounced increase in plasma corticoid levels. This also suggests that an increase in adrenal responsiveness to endogenous ACTH occurs during gestation. No detectable changes in maternal plasma ACTH or corticoids were found in response to fetal hemorrhage, thus the fetal pituitary-adrenal axis can autonomously respond to stress.", "contents": "Developmental aspects of the pituitary-adrenal axis response to hemorrhagic stress in lamb fetuses in utero. Plasma ACTH and corticosteroid concentrations were measured by radioimmunoassay in chronically catheterized fetuses of 32 pregnant sheep. Fetal plasma ACTH levels 38+/-5 pg/ml (means+/-SEM) were slightly (P < 0.05) lower than maternal 54+/-4 pg/ml levels. No general rise in fetal plasma ACTH concentration was noted before 140 days gestation; however, fetal plasma corticoid levels began to increase after about 125 days. This suggested that an increase in fetal adrenal responsiveness to endogenous ACTH occurred during gestation. Hemorrhage of 15% of estimated blood volume decreased mean arterial pressure from 54+/-3 to 36+/-3 torr and increased plasma ACTH from 30+/-5 to 130+/-30 pg/ml in fetuses older than 0.80 gestation. In fetuses younger than 0.67 gestation, 15% hemorrhage caused no change in plasma ACTH levels despite a significant fall in mean arterial pressure. This suggests that system(s) subserving the ACTH response to mild hemorrhage are either absent or nonfunctional in the younger fetuses. The hemorrhage-induced increase in plasma ACTH levels was associated with a small rise in plasma corticoids in fetuses younger than 0.94 gestation. In older fetuses, a similar increase in plasma ACTH was associated with a pronounced increase in plasma corticoid levels. This also suggests that an increase in adrenal responsiveness to endogenous ACTH occurs during gestation. No detectable changes in maternal plasma ACTH or corticoids were found in response to fetal hemorrhage, thus the fetal pituitary-adrenal axis can autonomously respond to stress."}
{"id": "PMID:202614", "title": "Differences in oxygen metabolism of phagocytosing monocytes and neutrophils.", "content": "The oxidative metabolism of monocytes and polymorphonuclear leukocytes from human peripheral blood was studied in resting and phagocytosing cells. Monocytes, like neutrophils, showed an increase in oxygen consumption during phagocytosis with a concurrent release of superoxide anions and hydrogen peroxide. Both oxygen products are highly reactive agents with potential bactericidal activity. Neutrophils consumed two and a half times as much oxygen, generated about twice as much superoxide, and released five times as much hydrogen peroxide as monocytes did. Monocytes generated superoxide and hydrogen peroxide at equivalent rates.Antimycin A, a specific mitochondrial respiratory chain inhibitor, depressed the oxygen consumption of monocytes by congruent with70% but had no effect on neutrophil respiration. Therefore, the oxygen consumed by phagocytosing monocytes appeared to be metabolized in two distinct processes: congruent with30% of the oxygen is converted to hydrogen peroxide, whereas the remaining 70% is metabolized via the mitochondrial respiratory chain. The release of superoxide and hydrogen peroxide was unaffected by antimycin in either cell type. Phagocytosis of zymosan particles by monocytes was nearly abolished by antimycin, whereas no effect was noted with neutrophils. Thus, phagocytosis appears to be highly dependent on oxidative phosphorylation in monocytes but not in polymorphonuclear leukocytes. Moreover, in monocytes treated with antimycin, an addition of opsonized zymosan particles induced stimulation of the oxidative metabolism without occurrence of ingestion.", "contents": "Differences in oxygen metabolism of phagocytosing monocytes and neutrophils. The oxidative metabolism of monocytes and polymorphonuclear leukocytes from human peripheral blood was studied in resting and phagocytosing cells. Monocytes, like neutrophils, showed an increase in oxygen consumption during phagocytosis with a concurrent release of superoxide anions and hydrogen peroxide. Both oxygen products are highly reactive agents with potential bactericidal activity. Neutrophils consumed two and a half times as much oxygen, generated about twice as much superoxide, and released five times as much hydrogen peroxide as monocytes did. Monocytes generated superoxide and hydrogen peroxide at equivalent rates.Antimycin A, a specific mitochondrial respiratory chain inhibitor, depressed the oxygen consumption of monocytes by congruent with70% but had no effect on neutrophil respiration. Therefore, the oxygen consumed by phagocytosing monocytes appeared to be metabolized in two distinct processes: congruent with30% of the oxygen is converted to hydrogen peroxide, whereas the remaining 70% is metabolized via the mitochondrial respiratory chain. The release of superoxide and hydrogen peroxide was unaffected by antimycin in either cell type. Phagocytosis of zymosan particles by monocytes was nearly abolished by antimycin, whereas no effect was noted with neutrophils. Thus, phagocytosis appears to be highly dependent on oxidative phosphorylation in monocytes but not in polymorphonuclear leukocytes. Moreover, in monocytes treated with antimycin, an addition of opsonized zymosan particles induced stimulation of the oxidative metabolism without occurrence of ingestion."}
{"id": "PMID:202615", "title": "Rat intestine secretes discoid high density lipoprotein.", "content": "High density lipoprotein was isolated from pooled rat serum and mesenteric lymph of lymph fistula rats. In most experiments, 5,5'-dithionitrobenzoic acid, an inhibitor of the enzyme lecithin:cholesterol acyltransferase, was added during the collection of lymph to prevent modification of the lipid composition of newly secreted lipoproteins. Negative staining electron microscopy of lymph high density lipoprotein revealed discoidal particles (190+/-3 x 55+/-1 A) which tended to form rouleaux, smaller spherical particles were also present. Serum high density lipoprotein contained only spherical particles (diameter 93+/-4 A). Lipid analysis showed that lymph high density lipoprotein was enriched in phospholipid and deficient in cholesterol esters when compared to serum high density lipoprotein. The phospholipid to cholesterol esters ratio was greatest in basal lymph high density lipoprotein when compared to fatty lymph and serum high density lipoprotein. From analysis of the lipid compositional data and direct particle measurement by electron microscopy, it could be determined that congruent with50% of basal lymph high density lipoprotein and 30% of fatty lymph high density lipoprotein was discoid. Basal lymph high density lipoprotein was enriched in apoA-I and deficient in the arginine-rich peptide, and the apoprotein composition of fatty lymph high density lipoprotein more closely resembled serum. These observations demonstrate that intestinal lymph contains two types of high density lipoprotein particles, a discoid nascent particle deficient in cholesterol ester and rich in apoA-I, and spherical high density lipoprotein derived from plasma. A significant amount of lymph high density lipoprotein appears to be secreted by the intestine.", "contents": "Rat intestine secretes discoid high density lipoprotein. High density lipoprotein was isolated from pooled rat serum and mesenteric lymph of lymph fistula rats. In most experiments, 5,5'-dithionitrobenzoic acid, an inhibitor of the enzyme lecithin:cholesterol acyltransferase, was added during the collection of lymph to prevent modification of the lipid composition of newly secreted lipoproteins. Negative staining electron microscopy of lymph high density lipoprotein revealed discoidal particles (190+/-3 x 55+/-1 A) which tended to form rouleaux, smaller spherical particles were also present. Serum high density lipoprotein contained only spherical particles (diameter 93+/-4 A). Lipid analysis showed that lymph high density lipoprotein was enriched in phospholipid and deficient in cholesterol esters when compared to serum high density lipoprotein. The phospholipid to cholesterol esters ratio was greatest in basal lymph high density lipoprotein when compared to fatty lymph and serum high density lipoprotein. From analysis of the lipid compositional data and direct particle measurement by electron microscopy, it could be determined that congruent with50% of basal lymph high density lipoprotein and 30% of fatty lymph high density lipoprotein was discoid. Basal lymph high density lipoprotein was enriched in apoA-I and deficient in the arginine-rich peptide, and the apoprotein composition of fatty lymph high density lipoprotein more closely resembled serum. These observations demonstrate that intestinal lymph contains two types of high density lipoprotein particles, a discoid nascent particle deficient in cholesterol ester and rich in apoA-I, and spherical high density lipoprotein derived from plasma. A significant amount of lymph high density lipoprotein appears to be secreted by the intestine."}
{"id": "PMID:202616", "title": "Effects of d-amphetamine and strychnine on cycloheximide- and diethyldithiocarbamate-induced amnesia in mice.", "content": "Groups of C57BL/6J mice were administred cycloheximide (CYC) 30 min before or immediately after training on a passive avoidance task and tested 72 hr later. Some CYC-pretreated groups were given strychnine or d-amphetamine (d-amp) immediately after training and others were given d-amp 1 hr after training. Other groups were given diethyldithiocarbamate (DDC) at various times before or after training. Some DDC-pretreated groups were gived-amp or strychnine as described above for CYC groups. Immediate posttraining administration of 5 mg/kg d-amp, but not strychnine, prevented amnesia in CYC-pretreated mice. The DDC induced an apparent amnesia when administered from 30 min before training to 3 hr after training.  Posttraining administration of d-amp or strychnine did not prevent DDC-induced amnesia. These results are discussed in relation to previous suggestions that CYC- and DDC-induced amnesia may be the result of a functional impairment of catecholamine neurotransmitter systems by these drugs.", "contents": "Effects of d-amphetamine and strychnine on cycloheximide- and diethyldithiocarbamate-induced amnesia in mice. Groups of C57BL/6J mice were administred cycloheximide (CYC) 30 min before or immediately after training on a passive avoidance task and tested 72 hr later. Some CYC-pretreated groups were given strychnine or d-amphetamine (d-amp) immediately after training and others were given d-amp 1 hr after training. Other groups were given diethyldithiocarbamate (DDC) at various times before or after training. Some DDC-pretreated groups were gived-amp or strychnine as described above for CYC groups. Immediate posttraining administration of 5 mg/kg d-amp, but not strychnine, prevented amnesia in CYC-pretreated mice. The DDC induced an apparent amnesia when administered from 30 min before training to 3 hr after training.  Posttraining administration of d-amp or strychnine did not prevent DDC-induced amnesia. These results are discussed in relation to previous suggestions that CYC- and DDC-induced amnesia may be the result of a functional impairment of catecholamine neurotransmitter systems by these drugs."}
{"id": "PMID:202648", "title": "An attempt to separate mononuclear cells fused with human red blood cell-ghosts from a cell mixture treated with HVJ (Sendai virus) using a fluorescence activated cell sorter (FACS II).", "content": "Nucleated cells (Ehrlich ascites tumor cells or L strain cells) and human red blood cells (RBC)-ghosts were mixed and fused by ultraviolet-inactivated HVJ (Sendai virus). The cell mixture was stained with FITC conjugated anti-RBC ghost antiserum and then applied to FACS II apparatus. The apparatus sorted mononuclear cells fused with RBC-ghosts from the cell mixture on the basis of both the light scattering and fluorescence profiles. When the same procedure was carried out on a mixture containing cells and intact human RBC, the cells sorted by this method were cells into which hemoglobin had been injected. The sorted cells were capable of forming colonies in culture. This sorting method may be useful for collecting cells in which macromolecules have been injected artificially by fusion of RBC-ghosts enclosing macromolecules.", "contents": "An attempt to separate mononuclear cells fused with human red blood cell-ghosts from a cell mixture treated with HVJ (Sendai virus) using a fluorescence activated cell sorter (FACS II). Nucleated cells (Ehrlich ascites tumor cells or L strain cells) and human red blood cells (RBC)-ghosts were mixed and fused by ultraviolet-inactivated HVJ (Sendai virus). The cell mixture was stained with FITC conjugated anti-RBC ghost antiserum and then applied to FACS II apparatus. The apparatus sorted mononuclear cells fused with RBC-ghosts from the cell mixture on the basis of both the light scattering and fluorescence profiles. When the same procedure was carried out on a mixture containing cells and intact human RBC, the cells sorted by this method were cells into which hemoglobin had been injected. The sorted cells were capable of forming colonies in culture. This sorting method may be useful for collecting cells in which macromolecules have been injected artificially by fusion of RBC-ghosts enclosing macromolecules."}
{"id": "PMID:202650", "title": "Dose-response relationships in a microneutralization test for foot-and-mouth disease viruses.", "content": "Two-dimensional quantal microneutralization tests on foot-and-mouth disease viruses, in which neutralizing antibody activity was titrated against a serial range of virus doses, demonstrated a variety of dose-response curves some of which were rectilinear, others clearly curvilinear. Moreover, in the case of the non-linear responses obtained with some antisera, the shape of the curve was such that antibody titres recorded with doses of virus ranging from 10(3)-10(5) TCD50 were closely similar. Studies were carried out on the effect of varying the conditions of the test on the shape of the dose-response curve: significant differences were obtained after treatment of the antiserum-virus mixtures with anti-species globulin, and when the test was assayed in cells of differing susceptibility to infection.", "contents": "Dose-response relationships in a microneutralization test for foot-and-mouth disease viruses. Two-dimensional quantal microneutralization tests on foot-and-mouth disease viruses, in which neutralizing antibody activity was titrated against a serial range of virus doses, demonstrated a variety of dose-response curves some of which were rectilinear, others clearly curvilinear. Moreover, in the case of the non-linear responses obtained with some antisera, the shape of the curve was such that antibody titres recorded with doses of virus ranging from 10(3)-10(5) TCD50 were closely similar. Studies were carried out on the effect of varying the conditions of the test on the shape of the dose-response curve: significant differences were obtained after treatment of the antiserum-virus mixtures with anti-species globulin, and when the test was assayed in cells of differing susceptibility to infection."}
{"id": "PMID:202651", "title": "The genetic mapping of a defective LPS response gene in C3H/HeJ mice.", "content": "The expression of a defective LPS response gene Lps and the major urinary protein (Mup-1) are concordantly inherited in backcross (C3H/HeJ x C57BL/6J)F1 x C3H/HeJ mice, indicating genetic linkage of these loci. Mup-1 is known to be linked to the brown coat color locus on chromosome 4 in mice; thus Lps can now be assigned to chromosome 4. A value of 0.06 +/- 0.02 has been estimated for the recombination frequency between Mup-1 and Lps. We have used the polysyndactyly (Ps) mutation further to localize Lps on chromosome 4. Lps is located between the Mup-1 and Ps loci.", "contents": "The genetic mapping of a defective LPS response gene in C3H/HeJ mice. The expression of a defective LPS response gene Lps and the major urinary protein (Mup-1) are concordantly inherited in backcross (C3H/HeJ x C57BL/6J)F1 x C3H/HeJ mice, indicating genetic linkage of these loci. Mup-1 is known to be linked to the brown coat color locus on chromosome 4 in mice; thus Lps can now be assigned to chromosome 4. A value of 0.06 +/- 0.02 has been estimated for the recombination frequency between Mup-1 and Lps. We have used the polysyndactyly (Ps) mutation further to localize Lps on chromosome 4. Lps is located between the Mup-1 and Ps loci."}
{"id": "PMID:202652", "title": "Correlation between the ability of tumor cells to resist humoral immune attack and their ability to synthesize lipid.", "content": "Agents that increase (certain metabolic inhibitors, chemotherapeutic agents, and x-irradiation), decrease (hormones), or have no effect (hyperthermia) on the susceptibility of line-1 and line-10 guinea pig hepatoma cells to humoral immune attack were studied for their effects on the ability of these tumor cells to synthesize macromolecules. A correlation was found between the drug-induced increase in sensitivity of these cells to antibody-C mediated killing and the loss of their ability to incorporate fatty acids into complex cellular lipids. Similarly, the hormone-induced increase in resistance of the cells to killing was accompanied by an enhancement in complex lipid synthesis by these cells was also observed after the cells were exposed to physical means of insult (x-irradiation or hyperthermia). No correlation was found between the sensitivity of the cells to antibody-C mediated killing and their ability to synthesize DNA, RNA, protein, or complex carbohydrate, or their capacity for de novo lipid synthesis as measured by incorporation of acetate and glycerol into cellular macromolecules. The assembly of free fatty acids into complex lipid moieties is therefore proposed to be of fundamental importance for the ability of the tumor cells to resist humoral immune killing.", "contents": "Correlation between the ability of tumor cells to resist humoral immune attack and their ability to synthesize lipid. Agents that increase (certain metabolic inhibitors, chemotherapeutic agents, and x-irradiation), decrease (hormones), or have no effect (hyperthermia) on the susceptibility of line-1 and line-10 guinea pig hepatoma cells to humoral immune attack were studied for their effects on the ability of these tumor cells to synthesize macromolecules. A correlation was found between the drug-induced increase in sensitivity of these cells to antibody-C mediated killing and the loss of their ability to incorporate fatty acids into complex cellular lipids. Similarly, the hormone-induced increase in resistance of the cells to killing was accompanied by an enhancement in complex lipid synthesis by these cells was also observed after the cells were exposed to physical means of insult (x-irradiation or hyperthermia). No correlation was found between the sensitivity of the cells to antibody-C mediated killing and their ability to synthesize DNA, RNA, protein, or complex carbohydrate, or their capacity for de novo lipid synthesis as measured by incorporation of acetate and glycerol into cellular macromolecules. The assembly of free fatty acids into complex lipid moieties is therefore proposed to be of fundamental importance for the ability of the tumor cells to resist humoral immune killing."}
{"id": "PMID:202653", "title": "Identification of lipids associated with the ability of tumor cells to resist humoral immune attack.", "content": "Certain metabolic inhibitors or chemotherapeutic agents that increase the susceptibility of line-1 or line-10 guinea pig hepatoma cells to humoral immune attack were studied for their effects on the ability of the cells to synthesize lipids. A direct correlation was found between the drug-induced increase in sensitivity to antibody-C mediated killing and the inhibition of the ability of the cells to incorporate acetate, glycerol, and fatty acids into complex cellular lipids. Drug-treated cells recultured in drug-free medium regained their resistance to antibody-C mediated killing; these cells recovered their ability for complex lipid synthesis at this time. Thin layer chromatography of CHCl3:CH3OH lipid extracts from these cells indicated that the drug-induced increase in susceptibility to humoral immune attack correlated with the inhibition of acetate, glycerol, and fatty acid incorporation into cardiolipin and triglyceride in line-10 cells and the inhibition of incorporation of these compounds into cardiolipin alone in line-1 cells. No direct correlation was found between the sensitivity of the cells to humoral immune attack and the ability of the cells to incorporate precursors of lipid synthesis into other lipid moieties (sphyngomyelin, phosphatidyl serine, phosphatidyl choline, phosphatidyl glycerol, or cholesterol esters). The synthesis of cardiolipin and triglycerides, therefore, appears to be associated with the mechanism whereby these tumor cells resist antibody-C mediated killing.", "contents": "Identification of lipids associated with the ability of tumor cells to resist humoral immune attack. Certain metabolic inhibitors or chemotherapeutic agents that increase the susceptibility of line-1 or line-10 guinea pig hepatoma cells to humoral immune attack were studied for their effects on the ability of the cells to synthesize lipids. A direct correlation was found between the drug-induced increase in sensitivity to antibody-C mediated killing and the inhibition of the ability of the cells to incorporate acetate, glycerol, and fatty acids into complex cellular lipids. Drug-treated cells recultured in drug-free medium regained their resistance to antibody-C mediated killing; these cells recovered their ability for complex lipid synthesis at this time. Thin layer chromatography of CHCl3:CH3OH lipid extracts from these cells indicated that the drug-induced increase in susceptibility to humoral immune attack correlated with the inhibition of acetate, glycerol, and fatty acid incorporation into cardiolipin and triglyceride in line-10 cells and the inhibition of incorporation of these compounds into cardiolipin alone in line-1 cells. No direct correlation was found between the sensitivity of the cells to humoral immune attack and the ability of the cells to incorporate precursors of lipid synthesis into other lipid moieties (sphyngomyelin, phosphatidyl serine, phosphatidyl choline, phosphatidyl glycerol, or cholesterol esters). The synthesis of cardiolipin and triglycerides, therefore, appears to be associated with the mechanism whereby these tumor cells resist antibody-C mediated killing."}
{"id": "PMID:202655", "title": "In vitro mitogenic stimulation of murine spleen cells by herpes simplex virus.", "content": "Spleen cells of B6 mice not previously immunized were induced to DNA synthesis by supernatants from HSV-infected tissue culture. The stimulatory principle could be passed through a 45-micrometer filter and sedimented at 100,000 x G. It was abolished by UV light, heating at 56 degrees C, and by an anti-HSV serum. The possibility that the observed stimulation was caused by LPS was therefore excluded, and there was a-so no indication of mycoplasma contamination. Partial purification of spleen cells from macrophages resulted in an increased stimulation by HSV. From experiments with nylon columns, anti-theta antibody, and nude mice it was concluded that HSV acted as a B cell mitogen. Strains of both HSV types 1 and 2 were stimulatory for B6 spleen cells. Of nine freshly isolated HSV strains with identical passage history (twice in HEF) four were strongly stimulatory, three showed a moderate stimulation, and two did not stimulate. Spleen cells from A/J and DBA/2 mice were stimulated to the same extent by HSV (WAL) as spleen cells from B6 mice. No viral replication was demonstrable in B6 spleen cell cultures stimulated for DNA synthesis by HSV. Thus our study demonstrates induction of cellular DNA synthesis in B lymphocytes by HSV which is abolished by inactivation of the virus.", "contents": "In vitro mitogenic stimulation of murine spleen cells by herpes simplex virus. Spleen cells of B6 mice not previously immunized were induced to DNA synthesis by supernatants from HSV-infected tissue culture. The stimulatory principle could be passed through a 45-micrometer filter and sedimented at 100,000 x G. It was abolished by UV light, heating at 56 degrees C, and by an anti-HSV serum. The possibility that the observed stimulation was caused by LPS was therefore excluded, and there was a-so no indication of mycoplasma contamination. Partial purification of spleen cells from macrophages resulted in an increased stimulation by HSV. From experiments with nylon columns, anti-theta antibody, and nude mice it was concluded that HSV acted as a B cell mitogen. Strains of both HSV types 1 and 2 were stimulatory for B6 spleen cells. Of nine freshly isolated HSV strains with identical passage history (twice in HEF) four were strongly stimulatory, three showed a moderate stimulation, and two did not stimulate. Spleen cells from A/J and DBA/2 mice were stimulated to the same extent by HSV (WAL) as spleen cells from B6 mice. No viral replication was demonstrable in B6 spleen cell cultures stimulated for DNA synthesis by HSV. Thus our study demonstrates induction of cellular DNA synthesis in B lymphocytes by HSV which is abolished by inactivation of the virus."}
{"id": "PMID:202656", "title": "Characterization of a fetal calf serum-derived molecule reactive with human natural antibodies: its occurrence in tissue culture-grown type C RNA viruses.", "content": "By means of a sensitive radioimmunoprecipitation (RIP) assay, simian sarcoma virus-simian sarcoma-associated virus (SSV-SSAV), purified from culture fluids of infected normal rat kidney (NRK) cells, was shown to acquire a surface antigen from serum used in the tissue culture medium. This antigen, which was acquired when serum from either fetal calf, horse, swine, rabbit, or chicken origin was used, accounted for a substantial portion (but not all) of the total precipitating activity exhibited by natural human antibodies for membrane-associated antigens of these viruses. By 1) alcohol precipitation, concanavalin A chromatography, and Sephadex G-150 filtration of fetal calf serum (FCS) proteins or 2) chromatography of serum proteins over a human IgG-containing immunoaffinity column, a glycoprotein of approximately 55,000 daltons has been identified which is a minor constituent of FCS (less than 0.1% of total protein) and has the antigenic capacity of whole FCS.", "contents": "Characterization of a fetal calf serum-derived molecule reactive with human natural antibodies: its occurrence in tissue culture-grown type C RNA viruses. By means of a sensitive radioimmunoprecipitation (RIP) assay, simian sarcoma virus-simian sarcoma-associated virus (SSV-SSAV), purified from culture fluids of infected normal rat kidney (NRK) cells, was shown to acquire a surface antigen from serum used in the tissue culture medium. This antigen, which was acquired when serum from either fetal calf, horse, swine, rabbit, or chicken origin was used, accounted for a substantial portion (but not all) of the total precipitating activity exhibited by natural human antibodies for membrane-associated antigens of these viruses. By 1) alcohol precipitation, concanavalin A chromatography, and Sephadex G-150 filtration of fetal calf serum (FCS) proteins or 2) chromatography of serum proteins over a human IgG-containing immunoaffinity column, a glycoprotein of approximately 55,000 daltons has been identified which is a minor constituent of FCS (less than 0.1% of total protein) and has the antigenic capacity of whole FCS."}
{"id": "PMID:202658", "title": "Labeling of high density lipoproteins with [3H] acetic anhydride.", "content": "Rat serum HDL was labeled by reaction with [3H] acetic anhydride at pH 7.2 for 30 min at room temperature by a modification of the method of Montelaro and Rueckert (1975. J. Biol. Chem. 250: 1413). Protein specific activities of 60 dpm/ng were achieved. Seven percent of the label was in lipid, of which 92 percent was recovered in phospholipid. The labeled HDL migrated as a single band as seen by electrophoretic or column chromatographic analysis. When the labeled HDL was injected into rats without re-isolation, the biological half-life was not significantly different from HDL labeled in vitro with 125I or in vivo with amino acids. All of the apoproteins were labeled; their specific activities were closer to one another than those obtained with 125I. For some applications, acetylation may provide a useful alternative to the 125I labeling procedure.", "contents": "Labeling of high density lipoproteins with [3H] acetic anhydride. Rat serum HDL was labeled by reaction with [3H] acetic anhydride at pH 7.2 for 30 min at room temperature by a modification of the method of Montelaro and Rueckert (1975. J. Biol. Chem. 250: 1413). Protein specific activities of 60 dpm/ng were achieved. Seven percent of the label was in lipid, of which 92 percent was recovered in phospholipid. The labeled HDL migrated as a single band as seen by electrophoretic or column chromatographic analysis. When the labeled HDL was injected into rats without re-isolation, the biological half-life was not significantly different from HDL labeled in vitro with 125I or in vivo with amino acids. All of the apoproteins were labeled; their specific activities were closer to one another than those obtained with 125I. For some applications, acetylation may provide a useful alternative to the 125I labeling procedure."}
{"id": "PMID:202659", "title": "Metabolsim of apoB and apoC lipoproteins in man: kinetic studies in normal and hyperlipoproteininemic subjects.", "content": "The kinetics of apolipoproteins B and C were studied in 14 normal and hyperlipoproteinemic subjects after injection of exogenously (125)I-labeled very low density lipoprotein (VLDL) particles. Plasma radioactivities of apoB and apoC were determined over a period of 4 days in VLDL (d < 1.006) and total radioactivity in intermediate (IDL) (1.006 < d < 1.019), low (LDL) (1.019 < d < 1.063), and high (HDL) (1.063 < d < 1.21) density lipoproteins. The data were analyzed by the use of a model, developed mostly from these data, with the following results. The VLDL particle undergoes a series of incremental density changes, most likely due to a number of delipidation steps, during which apoB stays with the particle until the density reaches the IDL range. There is, however, a loss of apoC associated with these delipidation steps. In our normal subjects, all IDL apoB eventually becomes LDL. In our hyperlipemic subjects some of the apoB on IDL is also degraded directly. The apoC lost by VLDL and IDL recycles to HDL, and most of it is picked up again by newly synthesized VLDL. There is a slowdown of the stepwise delipidation process in all hyperlipemic individuals studied. Three additional features became apparent in the type III subjects. First, there is a significant increase (a factor of 2 compared to normal) in the apoB synthesis rate by way of VLDL; second, there is an induced direct apoB synthesis pathway by way of IDL (and/or LDL); third, a bypass of the regular stepwise VLDL delipidation pathway is induced by which VLDL particles lose apoC but none of their apoB, thereby forming a new particle with metabolic properties similar to LDL, but with a density still in the VLDL density range. Two type III patients treated with nicotinic acid and clofibrate showed a sharp decrease in their VLDL apoB synthesis rates. This was somewhat compensated by an increased IDL apoB synthesis rate. A type I patient on a medium chain triglyceride diet also showed a number of metabolic changes, including reduced VLDL apoB synthesis and the induction of considerable IDL and/or LDL apoB synthesis.", "contents": "Metabolsim of apoB and apoC lipoproteins in man: kinetic studies in normal and hyperlipoproteininemic subjects. The kinetics of apolipoproteins B and C were studied in 14 normal and hyperlipoproteinemic subjects after injection of exogenously (125)I-labeled very low density lipoprotein (VLDL) particles. Plasma radioactivities of apoB and apoC were determined over a period of 4 days in VLDL (d < 1.006) and total radioactivity in intermediate (IDL) (1.006 < d < 1.019), low (LDL) (1.019 < d < 1.063), and high (HDL) (1.063 < d < 1.21) density lipoproteins. The data were analyzed by the use of a model, developed mostly from these data, with the following results. The VLDL particle undergoes a series of incremental density changes, most likely due to a number of delipidation steps, during which apoB stays with the particle until the density reaches the IDL range. There is, however, a loss of apoC associated with these delipidation steps. In our normal subjects, all IDL apoB eventually becomes LDL. In our hyperlipemic subjects some of the apoB on IDL is also degraded directly. The apoC lost by VLDL and IDL recycles to HDL, and most of it is picked up again by newly synthesized VLDL. There is a slowdown of the stepwise delipidation process in all hyperlipemic individuals studied. Three additional features became apparent in the type III subjects. First, there is a significant increase (a factor of 2 compared to normal) in the apoB synthesis rate by way of VLDL; second, there is an induced direct apoB synthesis pathway by way of IDL (and/or LDL); third, a bypass of the regular stepwise VLDL delipidation pathway is induced by which VLDL particles lose apoC but none of their apoB, thereby forming a new particle with metabolic properties similar to LDL, but with a density still in the VLDL density range. Two type III patients treated with nicotinic acid and clofibrate showed a sharp decrease in their VLDL apoB synthesis rates. This was somewhat compensated by an increased IDL apoB synthesis rate. A type I patient on a medium chain triglyceride diet also showed a number of metabolic changes, including reduced VLDL apoB synthesis and the induction of considerable IDL and/or LDL apoB synthesis."}
{"id": "PMID:202660", "title": "A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol.", "content": "The accurate quantitation of high density lipoproteins has recently assumed greater importance in view of studies suggesting their negative correlation with coronary heart disease. High density lipoproteins may be estimated by measuring cholesterol in the plasma fraction of d > 1.063 g/ml. A more practical approach is the specific precipitation of apolipoprotein B (apoB)-containing lipoproteins by sulfated polysaccharides and divalent cations, heparin-Mn(2+) being the most commonly used combination. The present heparin-Mn(2+) procedure was found to be reasonably specific and not often subject to large errors; however, 9% (primarily hypertriglyceridemic samples) of the 966 plasma samples treated with heparin-Mn(2+) had obvious supernatant turbidity, indicating incomplete sedimentation of apoB-associated lipoproteins. Furthermore, 48% of the nonturbid supernates contained more than 1 mg/dl (mean 2.5 mg/dl) of apoB-associated cholesterol when measured by a radial immunodiffusion procedure, indicating slight overestimation of HDL cholesterol. Determination of the extent of the unprecipitated apoB-associated lipoproteins by sensitive radioimmunoassay and of the amount of precipitated high density lipoprotein by radial immunodiffusion assay of apolipoproteins A-I and A-II at various heparin and Mn(2+) concentrations indicated that the usual heparin level (approximately 1.3 mg/ml) was adequate. However, a twofold increase in Mn(2+) concentration to 0.092 M improved precipitation of the apoB-associated lipoproteins without excessive precipitation of high density lipoprotein from plasma. This increased Mn(2+) level also provided improved sedimentation of the apoB-associated lipoproteins from hypertriglyceridemic plasma. Additional observations suggested that, for convenience, the heparin and Mn(2+) can be added simultaneously as a combined reagent, that samples can be incubated for 10 minutes at room temperature before centrifugation, and that turbid supernates from hypertriglyceridemic samples can usually be made free of apoB-associated lipoproteins by centrifugation at 12,000 g for 10 minutes.", "contents": "A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. The accurate quantitation of high density lipoproteins has recently assumed greater importance in view of studies suggesting their negative correlation with coronary heart disease. High density lipoproteins may be estimated by measuring cholesterol in the plasma fraction of d > 1.063 g/ml. A more practical approach is the specific precipitation of apolipoprotein B (apoB)-containing lipoproteins by sulfated polysaccharides and divalent cations, heparin-Mn(2+) being the most commonly used combination. The present heparin-Mn(2+) procedure was found to be reasonably specific and not often subject to large errors; however, 9% (primarily hypertriglyceridemic samples) of the 966 plasma samples treated with heparin-Mn(2+) had obvious supernatant turbidity, indicating incomplete sedimentation of apoB-associated lipoproteins. Furthermore, 48% of the nonturbid supernates contained more than 1 mg/dl (mean 2.5 mg/dl) of apoB-associated cholesterol when measured by a radial immunodiffusion procedure, indicating slight overestimation of HDL cholesterol. Determination of the extent of the unprecipitated apoB-associated lipoproteins by sensitive radioimmunoassay and of the amount of precipitated high density lipoprotein by radial immunodiffusion assay of apolipoproteins A-I and A-II at various heparin and Mn(2+) concentrations indicated that the usual heparin level (approximately 1.3 mg/ml) was adequate. However, a twofold increase in Mn(2+) concentration to 0.092 M improved precipitation of the apoB-associated lipoproteins without excessive precipitation of high density lipoprotein from plasma. This increased Mn(2+) level also provided improved sedimentation of the apoB-associated lipoproteins from hypertriglyceridemic plasma. Additional observations suggested that, for convenience, the heparin and Mn(2+) can be added simultaneously as a combined reagent, that samples can be incubated for 10 minutes at room temperature before centrifugation, and that turbid supernates from hypertriglyceridemic samples can usually be made free of apoB-associated lipoproteins by centrifugation at 12,000 g for 10 minutes."}
{"id": "PMID:202661", "title": "Effect of serum on ganglioside uptake and choleragen responsiveness of transformed mouse fibroblasts.", "content": "NCTC 2071 cells, transformed mouse fibroblasts, did not respond to choleragen when grown in chemically defined medium. When grown in medium containing 10 percent fetal calf serum, however, the cells accumulated cyclic AMP upon exposure to the toxin. Gangliosides isolated from the fetal calf serum were as effective as whole serum in inducing choleragen responsiveness in the cells. The putative choleragen receptor, the monosialo-ganglioside GM1, could not be detected by chemical analysis in cells exposed to serum. 3H-Labeled GM1 was detected in these cells, however, following sequential exposure to galactose oxidase and sodium borotritide. Thus, uptake of minute amounts of GM1 from serum by these cells sensitized them to choleragen.", "contents": "Effect of serum on ganglioside uptake and choleragen responsiveness of transformed mouse fibroblasts. NCTC 2071 cells, transformed mouse fibroblasts, did not respond to choleragen when grown in chemically defined medium. When grown in medium containing 10 percent fetal calf serum, however, the cells accumulated cyclic AMP upon exposure to the toxin. Gangliosides isolated from the fetal calf serum were as effective as whole serum in inducing choleragen responsiveness in the cells. The putative choleragen receptor, the monosialo-ganglioside GM1, could not be detected by chemical analysis in cells exposed to serum. 3H-Labeled GM1 was detected in these cells, however, following sequential exposure to galactose oxidase and sodium borotritide. Thus, uptake of minute amounts of GM1 from serum by these cells sensitized them to choleragen."}
{"id": "PMID:202664", "title": "Ionic mechanism for the generation of horizontal cell potentials in isolated axolotl retina.", "content": "The ionic mechanism of horizontal cell potentials was investigated in the isolated retina of the axolotl Ambystoma mexicanum. The membrane potentials of both receptors and horizontal cells were recorded intracellularly while the ionic composition of the medium flowing over the receptor side of the retina was changed. The membrane potential of the horizontal cell is highly depender side of the retina was changed. The membrane potential of the horizontal cell is highly dependent on the extracellular concentration of sodium. When the external ion concentration of either chloride or potassium was changed independently of the other, there were shifts in the membrane potential of the horizontal cell which could not be explained by changes in the equilibrium potential of these ions. If the external concentrations of both potassium and chloride ions were varied so that the product of their external concentrations did not change, the shift in the membrane potential of the horizontal cell was in the direction predicted by the Nernst equation. The results are consistent with the suggestion that in the dark the receptors release a synaptic transmitter which increases primarily the sodium conductance of the horizontal cell postsynaptic membrane.", "contents": "Ionic mechanism for the generation of horizontal cell potentials in isolated axolotl retina. The ionic mechanism of horizontal cell potentials was investigated in the isolated retina of the axolotl Ambystoma mexicanum. The membrane potentials of both receptors and horizontal cells were recorded intracellularly while the ionic composition of the medium flowing over the receptor side of the retina was changed. The membrane potential of the horizontal cell is highly depender side of the retina was changed. The membrane potential of the horizontal cell is highly dependent on the extracellular concentration of sodium. When the external ion concentration of either chloride or potassium was changed independently of the other, there were shifts in the membrane potential of the horizontal cell which could not be explained by changes in the equilibrium potential of these ions. If the external concentrations of both potassium and chloride ions were varied so that the product of their external concentrations did not change, the shift in the membrane potential of the horizontal cell was in the direction predicted by the Nernst equation. The results are consistent with the suggestion that in the dark the receptors release a synaptic transmitter which increases primarily the sodium conductance of the horizontal cell postsynaptic membrane."}
{"id": "PMID:202665", "title": "Appearance of early and late components of Epstein-Barr virus-associated membrane antigen in Daudi cells superinfected with P3HR-1 virus.", "content": "This study investigated the synthesis of membrane antigen (MA) as well as virus capsid antigen (VCA) and early antigen (EA) in Daudi cells which had been superinfected with the P3HR-1 strain of Epstein-Barr virus (EBV) and then treated with trypsin to remove initially absorbed MA-positive material from the cell surface. Synthesis of MA, VCA and EA was completely inhibited by puromycin. A marked reduction in the frequency of MA positive cells was observed in superinfected cells cultured in the presence of either cytosine arabinoside (Ara-C) or phosphonoacetate (PA); however, a small fraction of MA synthesis occurred, suggesting an inhibitor insensitive component in MA, A differential absorption of EBV antibody-positive human serum with the Ara-C treated or untreated infected cells detected two antigenically different components in MA: early (Ara-C insensitive) and late (Ara-C sensitive) MA.", "contents": "Appearance of early and late components of Epstein-Barr virus-associated membrane antigen in Daudi cells superinfected with P3HR-1 virus. This study investigated the synthesis of membrane antigen (MA) as well as virus capsid antigen (VCA) and early antigen (EA) in Daudi cells which had been superinfected with the P3HR-1 strain of Epstein-Barr virus (EBV) and then treated with trypsin to remove initially absorbed MA-positive material from the cell surface. Synthesis of MA, VCA and EA was completely inhibited by puromycin. A marked reduction in the frequency of MA positive cells was observed in superinfected cells cultured in the presence of either cytosine arabinoside (Ara-C) or phosphonoacetate (PA); however, a small fraction of MA synthesis occurred, suggesting an inhibitor insensitive component in MA, A differential absorption of EBV antibody-positive human serum with the Ara-C treated or untreated infected cells detected two antigenically different components in MA: early (Ara-C insensitive) and late (Ara-C sensitive) MA."}
{"id": "PMID:202666", "title": "Expression of early virus functions in human cytomegalovirus infected HEL cells: effect of ultraviolet light-irradiation of the virus.", "content": "Ultraviolet (u.v.) light-irradiation of human cytomegalovirus (HCMV) resulted in differential inactivation of virus capacities, e.g. induction of cell rounding, early antigens (EA), nuclear inclusion, HCMV DNA synthesis, cellular DNA synthesis, HCMV-specific DNA polymerase, cellular DNA polymerases and plaque production, while the capacity of HCMV to penetrate cell nuclei was not critically impaired. These results indicated that the virus-coded functions expressed after infection were responsible for sll these events except for HCMV-induced stimulation of cellular RNA synthesis which was enhanced by irradiation of the virus at a low dose of u.v. light (6600 ergs/mm2). In these experiments phosphonoacetic acid was effectively utilized to detect EA formation by immunofluorescent staining and to differentiate cellular DNA synthesis from virus DNA synthesis.", "contents": "Expression of early virus functions in human cytomegalovirus infected HEL cells: effect of ultraviolet light-irradiation of the virus. Ultraviolet (u.v.) light-irradiation of human cytomegalovirus (HCMV) resulted in differential inactivation of virus capacities, e.g. induction of cell rounding, early antigens (EA), nuclear inclusion, HCMV DNA synthesis, cellular DNA synthesis, HCMV-specific DNA polymerase, cellular DNA polymerases and plaque production, while the capacity of HCMV to penetrate cell nuclei was not critically impaired. These results indicated that the virus-coded functions expressed after infection were responsible for sll these events except for HCMV-induced stimulation of cellular RNA synthesis which was enhanced by irradiation of the virus at a low dose of u.v. light (6600 ergs/mm2). In these experiments phosphonoacetic acid was effectively utilized to detect EA formation by immunofluorescent staining and to differentiate cellular DNA synthesis from virus DNA synthesis."}
{"id": "PMID:202668", "title": "Multiple interactions between murine cytomegalovirus and lymphoid cells in vitro.", "content": "Spleen cultures from various strains of mice were infected in vitro with murine cytomegalovirus (MCMV). Infectious centres were established in a small proportion (not greater than 1%) of the cells. Virus could be rescued from these cells by co-cultivation with syngeneic or allogeneic fibroblasts, but the frequency of rescue could not be altered by incubation with cyclic nucleotide analogues, iododeoxyuridine, cortisol, or allogeneic spleen cells. In addition a smaller fraction of the cell population, possibly a sub-population of the infectious centres, replicated virus spontaneously. The presence of mitogens did not affect these interactions qualitatively or quantitatively. A third response to infection was an inhibition in DNA synthesis, which was suffered by unstimulated cultures and by cells transformed by concanavalin A and bacterial lipopolysaccharides, although overall cell viability was maintained. This response was also mediated by u.v.-inactivated virus.", "contents": "Multiple interactions between murine cytomegalovirus and lymphoid cells in vitro. Spleen cultures from various strains of mice were infected in vitro with murine cytomegalovirus (MCMV). Infectious centres were established in a small proportion (not greater than 1%) of the cells. Virus could be rescued from these cells by co-cultivation with syngeneic or allogeneic fibroblasts, but the frequency of rescue could not be altered by incubation with cyclic nucleotide analogues, iododeoxyuridine, cortisol, or allogeneic spleen cells. In addition a smaller fraction of the cell population, possibly a sub-population of the infectious centres, replicated virus spontaneously. The presence of mitogens did not affect these interactions qualitatively or quantitatively. A third response to infection was an inhibition in DNA synthesis, which was suffered by unstimulated cultures and by cells transformed by concanavalin A and bacterial lipopolysaccharides, although overall cell viability was maintained. This response was also mediated by u.v.-inactivated virus."}
{"id": "PMID:202669", "title": "The isoelectric point of the p30 polypeptide as a marker of mouse endogenous viruses.", "content": "The isoelectric point (PI) of the p30 polypeptide of members of the three known classes of mouse C-type endogenous viruses was determined both by column and by thin-layer gel isoelectric focusing. Each class was found to be characterized by a particular variant of p30 (isop30), with pI values of 6.1 for class I (ecotropic), 5.7 for class II (xenotropic), and 5.5 for class III (NZB, NIH, ATS124, also xenotropic). The 6.1-isop30 was found as a minor component of rat-grown NZB virus and of a number of laboratory strains of mouse C-type viruses.", "contents": "The isoelectric point of the p30 polypeptide as a marker of mouse endogenous viruses. The isoelectric point (PI) of the p30 polypeptide of members of the three known classes of mouse C-type endogenous viruses was determined both by column and by thin-layer gel isoelectric focusing. Each class was found to be characterized by a particular variant of p30 (isop30), with pI values of 6.1 for class I (ecotropic), 5.7 for class II (xenotropic), and 5.5 for class III (NZB, NIH, ATS124, also xenotropic). The 6.1-isop30 was found as a minor component of rat-grown NZB virus and of a number of laboratory strains of mouse C-type viruses."}
{"id": "PMID:202670", "title": "Characterization of snap-back RNAs in vesicular stomatitis defective interfering virus particles.", "content": "VSV defective interfering particles of various sizes and from several independent sources frequently contain plus and minus strand RNA. In many cases some of the complementary strands are covalently linked as snap-back molecules. Infectious particles on the other hand package little or no plus strands. Snap-back molecules from the three different sources examined so far vary in size but appear to conform to the same overall linear duplex structure with cross-links at the ends only. They each contain a base sequence which is a subset of the next larger one and appear to correspond to unique sequences in the L cistron of the genome. Possible origins for these snap-back molecules are discussed.", "contents": "Characterization of snap-back RNAs in vesicular stomatitis defective interfering virus particles. VSV defective interfering particles of various sizes and from several independent sources frequently contain plus and minus strand RNA. In many cases some of the complementary strands are covalently linked as snap-back molecules. Infectious particles on the other hand package little or no plus strands. Snap-back molecules from the three different sources examined so far vary in size but appear to conform to the same overall linear duplex structure with cross-links at the ends only. They each contain a base sequence which is a subset of the next larger one and appear to correspond to unique sequences in the L cistron of the genome. Possible origins for these snap-back molecules are discussed."}
{"id": "PMID:202671", "title": "Inverted complementary terminal sequences in single-stranded RNAs and snap-back RNAs from vesicular stomatitis defective interfering particles.", "content": "Complementary single-stranded RNAs from three independent VSV defective interfering particle (DI) sources examined can anneal and give rise to monomeric and multimeric circular and linear double-stranded structures observable by electron microscopy under aqueous conditions. When the RNA from the shortest of these DI is spread from 80% formamide solutions, as many as 32% of the molecules are circular, suggesting that the single-stranded RNAs contain inverted complementary terminal sequences. This is strongly supported by the isolation of the putative terminal sequences which rapidly become RNase resistant base-paired structures after melting and quick-cooling the RNA. RNase digestion yields a major and a minor component, 60 to 70 and 135 to 170 nucleotides long respectively. Snap-back DI RNAs also contain inverted complementary sequences at both ends of the plus and minus strands of the duplexes since nicking these at the ends gives rise to double-stranded molecules which can form monomeric and multimeric circular and linear molecules. Thus, snap-back molecules most likely contain a covalent linkage between or near complementary terminal sequences on the two complementary strands as schematically shown in Fig. 5D.", "contents": "Inverted complementary terminal sequences in single-stranded RNAs and snap-back RNAs from vesicular stomatitis defective interfering particles. Complementary single-stranded RNAs from three independent VSV defective interfering particle (DI) sources examined can anneal and give rise to monomeric and multimeric circular and linear double-stranded structures observable by electron microscopy under aqueous conditions. When the RNA from the shortest of these DI is spread from 80% formamide solutions, as many as 32% of the molecules are circular, suggesting that the single-stranded RNAs contain inverted complementary terminal sequences. This is strongly supported by the isolation of the putative terminal sequences which rapidly become RNase resistant base-paired structures after melting and quick-cooling the RNA. RNase digestion yields a major and a minor component, 60 to 70 and 135 to 170 nucleotides long respectively. Snap-back DI RNAs also contain inverted complementary sequences at both ends of the plus and minus strands of the duplexes since nicking these at the ends gives rise to double-stranded molecules which can form monomeric and multimeric circular and linear molecules. Thus, snap-back molecules most likely contain a covalent linkage between or near complementary terminal sequences on the two complementary strands as schematically shown in Fig. 5D."}
{"id": "PMID:202680", "title": "4-aminopyridine--a new drug tested in the treatment of Eaton-Lambert syndrome.", "content": "A 67 year old man with the myasthenic syndrome associated with small cell bronchogenic carcinoma was treated with a new drug, 4-aminopyridine. The muscle weakness showed marked improvement and electrophysiological examinations demonstrated restoration of neuromuscular transmission.", "contents": "4-aminopyridine--a new drug tested in the treatment of Eaton-Lambert syndrome. A 67 year old man with the myasthenic syndrome associated with small cell bronchogenic carcinoma was treated with a new drug, 4-aminopyridine. The muscle weakness showed marked improvement and electrophysiological examinations demonstrated restoration of neuromuscular transmission."}
{"id": "PMID:202681", "title": "Accessory nerve palsy.", "content": "After apparently uncomplicated excision of benign lesions in the posterior cervical triangle, two patients had shoulder pain. In one, neck pain and trapezius weakness were not prominent until one month after surgery. Inability to elevate the arm above the horizontal without externally rotating it, and prominent scapular displacement on arm abduction, but not on forward pushing movements, highlighted the trapezius dysfunction and differentiated it from serratus anterior weakness. Spinal accessory nerve lesions should be considered when minor surgical procedures, lymphadenitis, minor trauma, or tumours involved the posterior triangle of the neck.", "contents": "Accessory nerve palsy. After apparently uncomplicated excision of benign lesions in the posterior cervical triangle, two patients had shoulder pain. In one, neck pain and trapezius weakness were not prominent until one month after surgery. Inability to elevate the arm above the horizontal without externally rotating it, and prominent scapular displacement on arm abduction, but not on forward pushing movements, highlighted the trapezius dysfunction and differentiated it from serratus anterior weakness. Spinal accessory nerve lesions should be considered when minor surgical procedures, lymphadenitis, minor trauma, or tumours involved the posterior triangle of the neck."}
{"id": "PMID:202686", "title": "Occupational exposures to cyanide in Baltimore fire fighters.", "content": "A group of 479 fire fighters were investigated for routine exposure to hydrogen cyanide in the fire atmosphere using measurements of serum thiocyanate (SCN-). Our findings indicate that fire fighters were exposed to levels of hydrogen cyanide sufficient to raise their mean serum thiocyanate (SCN-) levels above that of controls. This elevation of serum SCN- occurred independently of smoking habits. Exposure to cyanide occurred much less frequently than previously studied exposures to carbon monoxide. Difficulties of correlating acute symptoms and the effectiveness of mask use with serum thiocyanate are discussed.", "contents": "Occupational exposures to cyanide in Baltimore fire fighters. A group of 479 fire fighters were investigated for routine exposure to hydrogen cyanide in the fire atmosphere using measurements of serum thiocyanate (SCN-). Our findings indicate that fire fighters were exposed to levels of hydrogen cyanide sufficient to raise their mean serum thiocyanate (SCN-) levels above that of controls. This elevation of serum SCN- occurred independently of smoking habits. Exposure to cyanide occurred much less frequently than previously studied exposures to carbon monoxide. Difficulties of correlating acute symptoms and the effectiveness of mask use with serum thiocyanate are discussed."}
{"id": "PMID:202687", "title": "Ectopic thyroid gland. A clinical study of 30 children and review.", "content": "Of 108 children being treated at our Institute for primary (nongoitrous) hypothyroidism, tests with radioactive iodine 131I uptake showed that 26 of them (24%) had an ectopic thyroid gland. Four euthyroid children also had anterior swellings of the neck which, in each case, proved to be an ectopic thyroid gland. Of the 30 children studied, 20 were girls and 10 were boys. Nine patients were diagnosed within the first year of life. Growth retardation, manifest in 20 patients, was the most common clinical finding at the time of diagnosis. Delayed bone age was a feature in all of them. Growth, after diagnosis was within normal limits in 83% of the infants who were treated within the first two years of life; only 50% of the children diagnosed later grew within normal limits. Similarly, mental function was best preserved in those patients in whom treatment was initiated within the first two years of life.", "contents": "Ectopic thyroid gland. A clinical study of 30 children and review. Of 108 children being treated at our Institute for primary (nongoitrous) hypothyroidism, tests with radioactive iodine 131I uptake showed that 26 of them (24%) had an ectopic thyroid gland. Four euthyroid children also had anterior swellings of the neck which, in each case, proved to be an ectopic thyroid gland. Of the 30 children studied, 20 were girls and 10 were boys. Nine patients were diagnosed within the first year of life. Growth retardation, manifest in 20 patients, was the most common clinical finding at the time of diagnosis. Delayed bone age was a feature in all of them. Growth, after diagnosis was within normal limits in 83% of the infants who were treated within the first two years of life; only 50% of the children diagnosed later grew within normal limits. Similarly, mental function was best preserved in those patients in whom treatment was initiated within the first two years of life."}
{"id": "PMID:202688", "title": "Rickets in children of rural origin in South Africa: is low dietary calcium a factor?", "content": "Studies of nine children 4 7/12 to 13 years of age who had rickets are presented. No evidence of renal abnormalities, vitamin D deficiency, or of the inherited varieties of rickets was found. The salient features were their rural origins, mild hypocalcemia with evidence of secondary hyperparathyroidism, and improvement with a normal diet that contained an average of 944 mg calcium/24 hours. It is proposed that the etiology of the rickets is related to low calcium intake with or without a high oxalate concentration in the diet.", "contents": "Rickets in children of rural origin in South Africa: is low dietary calcium a factor? Studies of nine children 4 7/12 to 13 years of age who had rickets are presented. No evidence of renal abnormalities, vitamin D deficiency, or of the inherited varieties of rickets was found. The salient features were their rural origins, mild hypocalcemia with evidence of secondary hyperparathyroidism, and improvement with a normal diet that contained an average of 944 mg calcium/24 hours. It is proposed that the etiology of the rickets is related to low calcium intake with or without a high oxalate concentration in the diet."}
{"id": "PMID:202690", "title": "Kinetics and mechanism of oxidation of promazine and promethazine by ferric perchlorate.", "content": "The equilibrium constants, kinetics, and mechanism of promazine and promethazine oxidation by ferric perchlorate were investigated at different temperatures and acidities using a stopped-flow spectrophotometric technique. The overall reaction can be represented as follows: (formula: see text) where P+ represents the radical cation corresponding to the phenothiazine derivative. The equilibrium quotients were evaluated at 1.00 M HClO4, 25.0 degrees, and ionic strength 1.0 M. The kinetics of reaction follow the equation: -d[P] divided by dt = k1[Fe3+][P]-k-1[Fe2+][P+] The rate constants k1 and k-1 are independent of acidity and are related to the corresponding equilibrium quotients.", "contents": "Kinetics and mechanism of oxidation of promazine and promethazine by ferric perchlorate. The equilibrium constants, kinetics, and mechanism of promazine and promethazine oxidation by ferric perchlorate were investigated at different temperatures and acidities using a stopped-flow spectrophotometric technique. The overall reaction can be represented as follows: (formula: see text) where P+ represents the radical cation corresponding to the phenothiazine derivative. The equilibrium quotients were evaluated at 1.00 M HClO4, 25.0 degrees, and ionic strength 1.0 M. The kinetics of reaction follow the equation: -d[P] divided by dt = k1[Fe3+][P]-k-1[Fe2+][P+] The rate constants k1 and k-1 are independent of acidity and are related to the corresponding equilibrium quotients."}
{"id": "PMID:202691", "title": "In vitro uptake of oral contraceptive steroids by magnesium trisilicate.", "content": "Some steroids used in oral contraceptives were adsorbed significantly by magnesium trisilicate. The adsorption affinity followed the sequence: ethindrone greater than mestranol greater than norethindrone greater than ethinyl estradiol. Adsorption data obtained at relatively low initial concentrations fitted a Langmuir plot; the values for monolayer adsorption ranged between 0.24 and 0.32 mg/g. At higher concentrations of the steroids, multilayer adsorption occurred. The results of desorption experiments made at 37 degrees in water and 0.05 N HCl suggested that desorption was incomplete and depended on the amount of steroid adsorbed. During the dissolution testing of a brand of contraceptive tablets containing norethindrone acetate, the presence of 0.5% (w/v) magnesium trisilicate in the medium resulted in almost complete reduction in the amount of the steroid remaining in solution after 1 hr.", "contents": "In vitro uptake of oral contraceptive steroids by magnesium trisilicate. Some steroids used in oral contraceptives were adsorbed significantly by magnesium trisilicate. The adsorption affinity followed the sequence: ethindrone greater than mestranol greater than norethindrone greater than ethinyl estradiol. Adsorption data obtained at relatively low initial concentrations fitted a Langmuir plot; the values for monolayer adsorption ranged between 0.24 and 0.32 mg/g. At higher concentrations of the steroids, multilayer adsorption occurred. The results of desorption experiments made at 37 degrees in water and 0.05 N HCl suggested that desorption was incomplete and depended on the amount of steroid adsorbed. During the dissolution testing of a brand of contraceptive tablets containing norethindrone acetate, the presence of 0.5% (w/v) magnesium trisilicate in the medium resulted in almost complete reduction in the amount of the steroid remaining in solution after 1 hr."}
{"id": "PMID:202693", "title": "Antihypertensive activity in rats for SQ 14,225, an orally active inhibitor of angiotensin I-converting enzyme.", "content": "SQ 14,225 (D-3-mercapto-2-methylpropanoyl-L-proline) markedly lowered the blood pressure of the renin-dependent aortic-ligated and two-kidney Goldblatt hypertensive rat and failed to reduce blood pressure in the one-kidney Goldblatt hypertensive rat. In the two-kidney Goldblatt rat, SQ 14,225 (p.o.) was about 10 times as potent as teprotide, the nonapeptide SQ 20,881 (s.c.). Oral doses of SQ 14,225 moderately reduced the blood pressure of the Wistar-Kyoto spontaneously hypertensive rat but not that of the normotensive Wistar-Kyoto rat. Bilateral nephrectomy abolished the antihypertensive activity of SQ 14,225 in the spontaneously hypertensive rat. SQ 14,225 and SQ 20,881 elicited parallel dose-response curves in the two-kidney renal hypertensive rat. Post-treatment of spontaneously hypertensive rats with either agent failed to augment the antihypertensive effect produced by effective doses of the other agent. The results suggest that SQ 14,225 acts primarily by inhibiting the renin-angiotensin system to reduce elevated blood pressure, especially in presumably renin-dependent models of hypertension.", "contents": "Antihypertensive activity in rats for SQ 14,225, an orally active inhibitor of angiotensin I-converting enzyme. SQ 14,225 (D-3-mercapto-2-methylpropanoyl-L-proline) markedly lowered the blood pressure of the renin-dependent aortic-ligated and two-kidney Goldblatt hypertensive rat and failed to reduce blood pressure in the one-kidney Goldblatt hypertensive rat. In the two-kidney Goldblatt rat, SQ 14,225 (p.o.) was about 10 times as potent as teprotide, the nonapeptide SQ 20,881 (s.c.). Oral doses of SQ 14,225 moderately reduced the blood pressure of the Wistar-Kyoto spontaneously hypertensive rat but not that of the normotensive Wistar-Kyoto rat. Bilateral nephrectomy abolished the antihypertensive activity of SQ 14,225 in the spontaneously hypertensive rat. SQ 14,225 and SQ 20,881 elicited parallel dose-response curves in the two-kidney renal hypertensive rat. Post-treatment of spontaneously hypertensive rats with either agent failed to augment the antihypertensive effect produced by effective doses of the other agent. The results suggest that SQ 14,225 acts primarily by inhibiting the renin-angiotensin system to reduce elevated blood pressure, especially in presumably renin-dependent models of hypertension."}
{"id": "PMID:202694", "title": "Purinergic inhibition of adrenergic transmission in rabbit blood vessels.", "content": "The effect of ATP and its congeners on the adrenergic neuroeffector transmission was evaluated in isolated blood vessels of the rabbit. ATP, ADP, AMP and adenosine inhibited the contractile response of the portal vein to adrenergic nerve stimulation, with a threshold concentration of the order of 0.1 muM and ED50 of about 1 microM. These agents, but not papaverine, inhibited the nerve stimulation-induced response in preference to the norepinephrine- or serotonin-induced response in the portal and saphenous veins and pulmonary and ear arteries. In the portal vein labeled with [3H]norepinephrine, ATP diminished the nerve stimulation-induced efflux of tritiated material. This nucleotide also reduced the KCl-induced tritium efflux but not the tyramine induced-efflux in the [3H]norepinephrine-labeled thoracic aorta. ATP had no significant effect on the uptake of [3H]norepinephrine in the portal vein, ear artery and thoracic aorta. Indomethacin and theophylline partially blocked the inhibitory action of ATP on the neurogenic constrictor response in some of the ear artery and saphenous vein preparations. Desipramine, atropine, propanolol, haloperidol and 2,2'-pyridylisatogen, a blocking agent against ATP in the taenia coli, were without such antagonistic effect. The results are consistent with a proposed negative feedback modulator role of ATP or a related purine compound in adrenergic transmission.", "contents": "Purinergic inhibition of adrenergic transmission in rabbit blood vessels. The effect of ATP and its congeners on the adrenergic neuroeffector transmission was evaluated in isolated blood vessels of the rabbit. ATP, ADP, AMP and adenosine inhibited the contractile response of the portal vein to adrenergic nerve stimulation, with a threshold concentration of the order of 0.1 muM and ED50 of about 1 microM. These agents, but not papaverine, inhibited the nerve stimulation-induced response in preference to the norepinephrine- or serotonin-induced response in the portal and saphenous veins and pulmonary and ear arteries. In the portal vein labeled with [3H]norepinephrine, ATP diminished the nerve stimulation-induced efflux of tritiated material. This nucleotide also reduced the KCl-induced tritium efflux but not the tyramine induced-efflux in the [3H]norepinephrine-labeled thoracic aorta. ATP had no significant effect on the uptake of [3H]norepinephrine in the portal vein, ear artery and thoracic aorta. Indomethacin and theophylline partially blocked the inhibitory action of ATP on the neurogenic constrictor response in some of the ear artery and saphenous vein preparations. Desipramine, atropine, propanolol, haloperidol and 2,2'-pyridylisatogen, a blocking agent against ATP in the taenia coli, were without such antagonistic effect. The results are consistent with a proposed negative feedback modulator role of ATP or a related purine compound in adrenergic transmission."}
{"id": "PMID:202697", "title": "Compensatory renal hypertrophy in hypophysectomized rats.", "content": "1. After hypophysectomy, both body and kidney weights fall, but at different rates. The rate at which the kidney decreases in weight is faster than that of the whole body.2. Seven days after unilateral nephrectomy, the dry weight of the remaining kidney of hypophysectomized rats, with the exception of rats which had been hypophysectomized for 2 days only, was always heavier than the kidney of control hypophysectomized rats of similar body weight.3. The difference between the dry weight of kidneys of unilaterally nephrectomized hypophysectomized and control hypophysectomized rats increased from 15% in early hypophysectomized (9 days) to about 35% in late hypophysectomized animals (23 days).4. The implantation of renal cortical cells from 2 day hypophysectomized rats into unilaterally nephrectomized control litter-mates inhibited compensatory renal hypertrophy in the latter. When a similar operation was made using kidney cells from animals which had been hypophysectomized for 23 days, there was no significant inhibition of compensatory renal hypertrophy.5. The renal contents of adenosine-3',5'-monophosphate (cyclic AMP) and of guanosine-3',5'-monophosphate (cyclic GMP) in rats hypophysectomized for 2 days were of the same order as those in normal rats, but were markedly lower in rats hypophysectomized for 23 days.6. In contrast to what had been observed in normal rats, in hypophysectomized (2 or 23 days) rats, unilateral nephrectomy did not affect significantly the levels of cyclic nucleotides in the remaining kidney.7. Cross-circulating anephric normal rats with 2 day hypophysectomized animals resulted in an increase of cyclic GMP content in their kidneys. The cross-circulation between anephric normal rats and 23 days hypophysectomized rats had no effect on the level of renal cyclic GMP of the latter.8. When rats hypophysectomized for either 2 or 23 days and which had been nephrectomized were cross-circulated with normal rats, there were no changes in the content of cyclic GMP in the kidneys of the latter.", "contents": "Compensatory renal hypertrophy in hypophysectomized rats. 1. After hypophysectomy, both body and kidney weights fall, but at different rates. The rate at which the kidney decreases in weight is faster than that of the whole body.2. Seven days after unilateral nephrectomy, the dry weight of the remaining kidney of hypophysectomized rats, with the exception of rats which had been hypophysectomized for 2 days only, was always heavier than the kidney of control hypophysectomized rats of similar body weight.3. The difference between the dry weight of kidneys of unilaterally nephrectomized hypophysectomized and control hypophysectomized rats increased from 15% in early hypophysectomized (9 days) to about 35% in late hypophysectomized animals (23 days).4. The implantation of renal cortical cells from 2 day hypophysectomized rats into unilaterally nephrectomized control litter-mates inhibited compensatory renal hypertrophy in the latter. When a similar operation was made using kidney cells from animals which had been hypophysectomized for 23 days, there was no significant inhibition of compensatory renal hypertrophy.5. The renal contents of adenosine-3',5'-monophosphate (cyclic AMP) and of guanosine-3',5'-monophosphate (cyclic GMP) in rats hypophysectomized for 2 days were of the same order as those in normal rats, but were markedly lower in rats hypophysectomized for 23 days.6. In contrast to what had been observed in normal rats, in hypophysectomized (2 or 23 days) rats, unilateral nephrectomy did not affect significantly the levels of cyclic nucleotides in the remaining kidney.7. Cross-circulating anephric normal rats with 2 day hypophysectomized animals resulted in an increase of cyclic GMP content in their kidneys. The cross-circulation between anephric normal rats and 23 days hypophysectomized rats had no effect on the level of renal cyclic GMP of the latter.8. When rats hypophysectomized for either 2 or 23 days and which had been nephrectomized were cross-circulated with normal rats, there were no changes in the content of cyclic GMP in the kidneys of the latter."}
{"id": "PMID:202698", "title": "Neuromuscular transmission in arterioles of guinea-pig submucosa.", "content": "1. Intracellular recordings were made from arterioles lying in the submucosa of guinea-pig small intestine. 2. Low frequency perivascular nerve stimulation evoked subthreshold excitatory junction potentials which facilitated. 3. Higher frequency stimulation caused summation of excitatory junction potentials and the initiation of muscle action potentials. 4. Arteriolar constriction was only observed following the initiation of a muscle action potential.", "contents": "Neuromuscular transmission in arterioles of guinea-pig submucosa. 1. Intracellular recordings were made from arterioles lying in the submucosa of guinea-pig small intestine. 2. Low frequency perivascular nerve stimulation evoked subthreshold excitatory junction potentials which facilitated. 3. Higher frequency stimulation caused summation of excitatory junction potentials and the initiation of muscle action potentials. 4. Arteriolar constriction was only observed following the initiation of a muscle action potential."}
{"id": "PMID:202699", "title": "Permeability of the post-synaptic membrane of an excitatory glutamate synapse to sodium and potassium.", "content": "1. The changes in permeability of the post-synaptic membrane at the insect skeletal neuromuscular junction caused by the excitatory transmitter and L-glutamate have been studied using the voltage clamp technique. 2. The reversal potential (ER) of the excitatory post-synaptic current and the glutamate current was +3 and +4 mV respectively. 3. ER of the synaptic current did not change when external K was altered between 0 and 20 mM, but did show a small positive shift in 40 mM external K. Reducing external Na to 1-10 mM changes ER by 12-18 mV. Reducing external Cl to to zero caused no change in ER. 4. It is proposed that the transmitter and L-glutamate cause an increase in permeability to Na and K, but not to Cl. 5. In normal saline, the ratio of the permeability increase to Na and K (delta PNa/delta PK) is 0.9. 6. The changes in ER caused by altering external K were similar to those predicted by the Goldman-Hodgkin-Katz equation, assuming delta PNa/delta PK stays constant. 7. The changes in ER caused by alterations of external Na are much less than those predicted by the Goldman equation. 8. No glutamate current could be recorded in Na- and Ca-free saline either at the resting potential or at depolarized or hyperpolarized membrane potentials. 9. It is proposed that the outward K current is dependent upon the inward Na current, and that the increase in K permeability is abolished in zero external Na.", "contents": "Permeability of the post-synaptic membrane of an excitatory glutamate synapse to sodium and potassium. 1. The changes in permeability of the post-synaptic membrane at the insect skeletal neuromuscular junction caused by the excitatory transmitter and L-glutamate have been studied using the voltage clamp technique. 2. The reversal potential (ER) of the excitatory post-synaptic current and the glutamate current was +3 and +4 mV respectively. 3. ER of the synaptic current did not change when external K was altered between 0 and 20 mM, but did show a small positive shift in 40 mM external K. Reducing external Na to 1-10 mM changes ER by 12-18 mV. Reducing external Cl to to zero caused no change in ER. 4. It is proposed that the transmitter and L-glutamate cause an increase in permeability to Na and K, but not to Cl. 5. In normal saline, the ratio of the permeability increase to Na and K (delta PNa/delta PK) is 0.9. 6. The changes in ER caused by altering external K were similar to those predicted by the Goldman-Hodgkin-Katz equation, assuming delta PNa/delta PK stays constant. 7. The changes in ER caused by alterations of external Na are much less than those predicted by the Goldman equation. 8. No glutamate current could be recorded in Na- and Ca-free saline either at the resting potential or at depolarized or hyperpolarized membrane potentials. 9. It is proposed that the outward K current is dependent upon the inward Na current, and that the increase in K permeability is abolished in zero external Na."}
{"id": "PMID:202700", "title": "Action of brown widow spider venom and botulinum toxin on the frog neuromuscular junction examined with the freeze-fracture technique.", "content": "1. Structural changes which normally accompany transmitter release at frog neuromuscular junctions are visualized with the freeze-fracture technique. The effects of brown widow spider venom and botulinum toxin were evaluated in terms of their ability to block or produce these structural changes. Changes produced by these neuropoisons were correlated with their known effects on neurotransmitter release. 3. Fusion of synaptic vesicles with the presynaptic plasmalemma, normally evoked by electrical stimulation, was abolished at neuromuscular junctions from frogs treated with botulinum toxin. 3. The concentration of large intramembranous particles in the presynaptic plasmalemma, an indication of the excess of synaptic vesicle fusion over recovery of synaptic vesicle membrane, was increased by treatment with brown widow spider venom, even in the presence of botulinum toxin. 4. When external calcium was present, sites of vesicle fusion induced by brown widow spider venom, as well as by electrical stimulation, were located mainly in the active zone. In the absence of external calcium, many plasmalemmal deformations, also though to be sites of vesicle fusion, were more evenly dispersed over the presynaptic surface of nerve terminals. 5. Botulinum toxin decreased the number of vesicle fusion sites in the active zone induced by spider venom in the presence of external calcium but had little effect on the number of fusion sites induced by spider venom in the absence of external calcium. 6. Nerve terminals soaked in a sodium-free Ringer solution were partially depleted of vesicles. Addition of spider venom to this Ringer did not cause additional depletion of vesicles. 7. Formation of cation-permeable channels in the presynaptic membrane could account for these effects of spider venom on the frog neuromuscular junction. Botulinum toxin blocks vesicle fusion by some means which is not yet understood.", "contents": "Action of brown widow spider venom and botulinum toxin on the frog neuromuscular junction examined with the freeze-fracture technique. 1. Structural changes which normally accompany transmitter release at frog neuromuscular junctions are visualized with the freeze-fracture technique. The effects of brown widow spider venom and botulinum toxin were evaluated in terms of their ability to block or produce these structural changes. Changes produced by these neuropoisons were correlated with their known effects on neurotransmitter release. 3. Fusion of synaptic vesicles with the presynaptic plasmalemma, normally evoked by electrical stimulation, was abolished at neuromuscular junctions from frogs treated with botulinum toxin. 3. The concentration of large intramembranous particles in the presynaptic plasmalemma, an indication of the excess of synaptic vesicle fusion over recovery of synaptic vesicle membrane, was increased by treatment with brown widow spider venom, even in the presence of botulinum toxin. 4. When external calcium was present, sites of vesicle fusion induced by brown widow spider venom, as well as by electrical stimulation, were located mainly in the active zone. In the absence of external calcium, many plasmalemmal deformations, also though to be sites of vesicle fusion, were more evenly dispersed over the presynaptic surface of nerve terminals. 5. Botulinum toxin decreased the number of vesicle fusion sites in the active zone induced by spider venom in the presence of external calcium but had little effect on the number of fusion sites induced by spider venom in the absence of external calcium. 6. Nerve terminals soaked in a sodium-free Ringer solution were partially depleted of vesicles. Addition of spider venom to this Ringer did not cause additional depletion of vesicles. 7. Formation of cation-permeable channels in the presynaptic membrane could account for these effects of spider venom on the frog neuromuscular junction. Botulinum toxin blocks vesicle fusion by some means which is not yet understood."}
{"id": "PMID:202704", "title": "Ultrastructural observations of experimental Naegleria meningoencephalitis in mice: intranuclear inclusions in amebae and host cells.", "content": "Primary amebic meningoencephalitis was experimentallly produced in mice through intranasal instillation of pathogenic Naegleria fowleri. Experimental animals had a 64% mortality with average time of onset of symtoms of death occurring on the 7-8th day following inoculation. Ultrastructural studies of the olfactory lobes from brains of dead (or sacrificed) animals revealed major concentrations of amebae in the perivascular regions; amebae were also seen to be under attack by host polymorphonuclear leukocytes, and in the lumina of blood vessels. Amebae in brain tissue contained 30 nm intranuclear particles arranged in clusters. In the brains of some mice, dead presumably as a result of amebic meningoencephalitis, particles and crystalloids were observed in the nuclei of degenerating cells of the central nervous system. Some alternatives are examined to explain a possible relationship between ameba intranuclear particles and mouse brain cell intranuclear inclusions.", "contents": "Ultrastructural observations of experimental Naegleria meningoencephalitis in mice: intranuclear inclusions in amebae and host cells. Primary amebic meningoencephalitis was experimentallly produced in mice through intranasal instillation of pathogenic Naegleria fowleri. Experimental animals had a 64% mortality with average time of onset of symtoms of death occurring on the 7-8th day following inoculation. Ultrastructural studies of the olfactory lobes from brains of dead (or sacrificed) animals revealed major concentrations of amebae in the perivascular regions; amebae were also seen to be under attack by host polymorphonuclear leukocytes, and in the lumina of blood vessels. Amebae in brain tissue contained 30 nm intranuclear particles arranged in clusters. In the brains of some mice, dead presumably as a result of amebic meningoencephalitis, particles and crystalloids were observed in the nuclei of degenerating cells of the central nervous system. Some alternatives are examined to explain a possible relationship between ameba intranuclear particles and mouse brain cell intranuclear inclusions."}
{"id": "PMID:202705", "title": "Effects of factors released from eggs and other agents on cyclic nucleotide concentrations of sea urchin spermatozoa.", "content": "Factors released from eggs (FRE) of the sea urchin, Strongylocentrotus purpuratus, caused up to 20-fold increases in sperm cyclic AMP levels after a 1-min incubation. Putative cyclic nucleotide phosphodiesterase inhibitors such as theophylline acted in a synergistic manner with FRE to cause even greater increases in sperm cyclic AMP levels. This effect appeared to be specific for egg factors since various hormones (triiodothyronine, norepinephrine, histamine), nucleosides (adenosine, guanosine), nucleophiles (axide), anaesthetics (procaine), ionophores (X537A, A23187), metals (Mn2+) and neurotransmitters (acetylcholine) did not increase sperm cyclic AMP levels. Various mammalian tissue extracts (serum, uterus, adrenal, ovary, lung) also had no effect. We suggest that the activity which elevates the cyclic AMP of sea urchin spermatozoa is specifically associated with sea urchin eggs.", "contents": "Effects of factors released from eggs and other agents on cyclic nucleotide concentrations of sea urchin spermatozoa. Factors released from eggs (FRE) of the sea urchin, Strongylocentrotus purpuratus, caused up to 20-fold increases in sperm cyclic AMP levels after a 1-min incubation. Putative cyclic nucleotide phosphodiesterase inhibitors such as theophylline acted in a synergistic manner with FRE to cause even greater increases in sperm cyclic AMP levels. This effect appeared to be specific for egg factors since various hormones (triiodothyronine, norepinephrine, histamine), nucleosides (adenosine, guanosine), nucleophiles (axide), anaesthetics (procaine), ionophores (X537A, A23187), metals (Mn2+) and neurotransmitters (acetylcholine) did not increase sperm cyclic AMP levels. Various mammalian tissue extracts (serum, uterus, adrenal, ovary, lung) also had no effect. We suggest that the activity which elevates the cyclic AMP of sea urchin spermatozoa is specifically associated with sea urchin eggs."}
{"id": "PMID:202706", "title": "Immunocytochemical localization of binding 'sites' for LH and hCG in preimplantation mouse embryos.", "content": "By using an immunoperoxidase antibody method, mouse blastocysts were found to bind specifically hCG and ovine LH but not FSH or the beta unit of hCG. Brown peroxidase reaction products were present in the morula and increased with the formation of the blastocoele. The LH/hCG binding 'sites' may be related to the initiation of steroidogenesis in the embryo.", "contents": "Immunocytochemical localization of binding 'sites' for LH and hCG in preimplantation mouse embryos. By using an immunoperoxidase antibody method, mouse blastocysts were found to bind specifically hCG and ovine LH but not FSH or the beta unit of hCG. Brown peroxidase reaction products were present in the morula and increased with the formation of the blastocoele. The LH/hCG binding 'sites' may be related to the initiation of steroidogenesis in the embryo."}
{"id": "PMID:202707", "title": "Preovulatory changes in ovarian cyclic AMP and prostaglandins in immature rats injected with PMSG.", "content": "In 28-day-old rats injected with PMSG, ovarian cyclic AMP and PGE and PGF increased 2 and 3-4 h respectively after the LH peak.", "contents": "Preovulatory changes in ovarian cyclic AMP and prostaglandins in immature rats injected with PMSG. In 28-day-old rats injected with PMSG, ovarian cyclic AMP and PGE and PGF increased 2 and 3-4 h respectively after the LH peak."}
{"id": "PMID:202708", "title": "Microbiological investigation of meat wholesale premises and beef carcases in Johannesburg.", "content": "Microbiological surveillance by swabbing meat wholesaler premises revealed ineffective cleaning and build-up of bacteria. Proper cleaning, sanitation and handling resulted in a vast improvement during 1975-77. Beef samples from the neck of carcases in the wholesale trade were investigated by microbiological methods. Excessive total bacterial counts were obtained from numerous carcases. Most carcases carried coliform organisms. Roughly 90% of carcases were contaminated with E. coli I; counts exceeded 10(3)/g in 18% of carcases tested. Twenty serotypes of Salmonella were identified. Salmonella contamination decreased from nearly 5% in 1975 to less than 0,5% in 1977, and S. aureus contamination from 52% to 36% during the same period. Approximately 30% of carcases revealed contamination with unidentified clostridial species. The results indicate the need for stricter control over the production and slaughter of animals and over the handling of carcases in the wholesale trade.", "contents": "Microbiological investigation of meat wholesale premises and beef carcases in Johannesburg. Microbiological surveillance by swabbing meat wholesaler premises revealed ineffective cleaning and build-up of bacteria. Proper cleaning, sanitation and handling resulted in a vast improvement during 1975-77. Beef samples from the neck of carcases in the wholesale trade were investigated by microbiological methods. Excessive total bacterial counts were obtained from numerous carcases. Most carcases carried coliform organisms. Roughly 90% of carcases were contaminated with E. coli I; counts exceeded 10(3)/g in 18% of carcases tested. Twenty serotypes of Salmonella were identified. Salmonella contamination decreased from nearly 5% in 1975 to less than 0,5% in 1977, and S. aureus contamination from 52% to 36% during the same period. Approximately 30% of carcases revealed contamination with unidentified clostridial species. The results indicate the need for stricter control over the production and slaughter of animals and over the handling of carcases in the wholesale trade."}
{"id": "PMID:202709", "title": "5-O-Alkylated derivatives of 5-hydroxy-2'-deoxyuridine as potential antiviral agents. Anti-herpes activity of 5-propynyloxy-2'-deoxyuridine.", "content": "Alkylation of 5-hydroxyuridine or 5-hydroxy-2'-deoxyuridine with various activated alkylating agents in the presence of 1 equiv of NaOH gave a series of new nucleoside analogues which were evaluated for antiviral activity against vaccinia virus, herpes simplex-1 virus, and vesicular stomatitis virus in both primary rabbit kidney cells and human skin fibroblasts. One of these analogues, 5-propynyloxy-2'-deoxyuridine, was a potent inhibitor of herpes simplex virus. Structure-activity considerations suggest that the anti-herpes activity is dependent on the integrity of the acetylene group since substitution of phenyl, p-nitrophenyl, vinyl, carboxamido, or carboxyl for the triple bond led to diminished antiviral activity.", "contents": "5-O-Alkylated derivatives of 5-hydroxy-2'-deoxyuridine as potential antiviral agents. Anti-herpes activity of 5-propynyloxy-2'-deoxyuridine. Alkylation of 5-hydroxyuridine or 5-hydroxy-2'-deoxyuridine with various activated alkylating agents in the presence of 1 equiv of NaOH gave a series of new nucleoside analogues which were evaluated for antiviral activity against vaccinia virus, herpes simplex-1 virus, and vesicular stomatitis virus in both primary rabbit kidney cells and human skin fibroblasts. One of these analogues, 5-propynyloxy-2'-deoxyuridine, was a potent inhibitor of herpes simplex virus. Structure-activity considerations suggest that the anti-herpes activity is dependent on the integrity of the acetylene group since substitution of phenyl, p-nitrophenyl, vinyl, carboxamido, or carboxyl for the triple bond led to diminished antiviral activity."}
{"id": "PMID:202710", "title": "The role of breast-feeding in the prevention of rotavirus infection.", "content": "Breast-fed infants are less susceptible to gastroenteritis than bottle-fed infants. Antibodies against rotavirus, the major pathogen of infantile gastroenteritis, were sought in human sera, colostrum and milk specimens by immunofluorescence. An experimental murine-rotavirus model was established by infecting the second litters of dams 4 weeks after infecting their first litters. Antibodies were absent from human and murine colostrum and milk specimens despite being present in virtually all sera, and the second mouse litters were as susceptible as the first. The inability of rotavirus to infect adult human beings and mice may prevent the formation of gut-derived antibody-secreting lymphocytes in milk, and thus prevent transmission of passive immunity. The association of bottle-feeding with rotavirus gastroenteritis appears to be the result of increased opportunity for spread of infection rather than of the absence of specific protective antibody.", "contents": "The role of breast-feeding in the prevention of rotavirus infection. Breast-fed infants are less susceptible to gastroenteritis than bottle-fed infants. Antibodies against rotavirus, the major pathogen of infantile gastroenteritis, were sought in human sera, colostrum and milk specimens by immunofluorescence. An experimental murine-rotavirus model was established by infecting the second litters of dams 4 weeks after infecting their first litters. Antibodies were absent from human and murine colostrum and milk specimens despite being present in virtually all sera, and the second mouse litters were as susceptible as the first. The inability of rotavirus to infect adult human beings and mice may prevent the formation of gut-derived antibody-secreting lymphocytes in milk, and thus prevent transmission of passive immunity. The association of bottle-feeding with rotavirus gastroenteritis appears to be the result of increased opportunity for spread of infection rather than of the absence of specific protective antibody."}
{"id": "PMID:202714", "title": "Cyanamide mediated syntheses under plausible primitive earth conditions. I. The synthesis of P1, P2 dideoxythymidine 5'-pyrophosphate.", "content": "When an aqueous solution (pH 7.0) of deoxythymidine 5'-phosphate, 4-amino-5-imidazolecarboxamide and cyanamide was dried and heated for 18 h at 60 degrees C, P1, P2-dideoxythymidine 5'-pyrophosphate (I) was formed in a 58% yield. Oligonucleotides were not detected in the reaction product. Under conditions employed in the above reaction, (I) was shown to be stable. In prebiotic polymerization reactions employing deoxythymidine 5'-triphosphate as the polymerizing species, (I) could therefore function as a primer and minimize the formation of cyclic nucleotides.", "contents": "Cyanamide mediated syntheses under plausible primitive earth conditions. I. The synthesis of P1, P2 dideoxythymidine 5'-pyrophosphate. When an aqueous solution (pH 7.0) of deoxythymidine 5'-phosphate, 4-amino-5-imidazolecarboxamide and cyanamide was dried and heated for 18 h at 60 degrees C, P1, P2-dideoxythymidine 5'-pyrophosphate (I) was formed in a 58% yield. Oligonucleotides were not detected in the reaction product. Under conditions employed in the above reaction, (I) was shown to be stable. In prebiotic polymerization reactions employing deoxythymidine 5'-triphosphate as the polymerizing species, (I) could therefore function as a primer and minimize the formation of cyclic nucleotides."}
{"id": "PMID:202715", "title": "Effect of dietary protein on the response of rainbow trout (Salmo gairdneri) to aflatoxin B1.", "content": "Diets containing either 49.5% or 32% casein or fish protein concentrate (FPC) were fed to young rainbow trout (Salmo gairdneri) for 12 months. Five levels [0, 2, 6, 18, and 54 parts per billion (ppb)] of aflatoxin B1 (AFB1) were given in each of four different diets. A 30-fish sample was taken at 6, 9, and 12 months to determine the influence of diet on the carcinogenicity of AFB1. Both levels of casein produced similar hepatoma incidences at each level of AFB1. The diet high in FPC produced more tumours than did the casein diets at 2, 6, and 18 ppb AFB1, whereas fish fed the diet low in FPC had a significantly (P less than 0.05) lower hepatoma incidence than did the other three groups. The liver size (percent body wt) was smaller at higher toxin levels in all instances. The growth of fish given 32% casein was less than that of the other groups.", "contents": "Effect of dietary protein on the response of rainbow trout (Salmo gairdneri) to aflatoxin B1. Diets containing either 49.5% or 32% casein or fish protein concentrate (FPC) were fed to young rainbow trout (Salmo gairdneri) for 12 months. Five levels [0, 2, 6, 18, and 54 parts per billion (ppb)] of aflatoxin B1 (AFB1) were given in each of four different diets. A 30-fish sample was taken at 6, 9, and 12 months to determine the influence of diet on the carcinogenicity of AFB1. Both levels of casein produced similar hepatoma incidences at each level of AFB1. The diet high in FPC produced more tumours than did the casein diets at 2, 6, and 18 ppb AFB1, whereas fish fed the diet low in FPC had a significantly (P less than 0.05) lower hepatoma incidence than did the other three groups. The liver size (percent body wt) was smaller at higher toxin levels in all instances. The growth of fish given 32% casein was less than that of the other groups."}
{"id": "PMID:202716", "title": "Carcinogenic effect of N-nitroso-2,6-dimethylmorpholine in Syrian golden hamsters.", "content": "N-Nitroso-2,6-dimethylmorpholine was intragastrically administered to Syrian golden hamsters at four different dose levels [74 mg/kg body wt = 1/5 median lethal dose (LD50); 37 mg/kg body wt = 1/10 LD50; 18 mg/kg body wt = 1/20 LD50; and 9 mg/kg body wt = 1/40 LD50]. Up to a 71% rate of pancreatic tumors was induced. These tumors were adenomas or adenocarcinomas of ductal origin. In addition, neoplasms developed in different percentages in the nasal cavities, larynx, trachea, lungs, liver, gallbladder, kidneys, and forestomach. The number of tumors induced was not significantly dose-dependent.", "contents": "Carcinogenic effect of N-nitroso-2,6-dimethylmorpholine in Syrian golden hamsters. N-Nitroso-2,6-dimethylmorpholine was intragastrically administered to Syrian golden hamsters at four different dose levels [74 mg/kg body wt = 1/5 median lethal dose (LD50); 37 mg/kg body wt = 1/10 LD50; 18 mg/kg body wt = 1/20 LD50; and 9 mg/kg body wt = 1/40 LD50]. Up to a 71% rate of pancreatic tumors was induced. These tumors were adenomas or adenocarcinomas of ductal origin. In addition, neoplasms developed in different percentages in the nasal cavities, larynx, trachea, lungs, liver, gallbladder, kidneys, and forestomach. The number of tumors induced was not significantly dose-dependent."}
{"id": "PMID:202717", "title": "Rescue of a transforming virus from a spontaneous nonproducing osteosarcoma in BALB/c mice.", "content": "Cells from spontaneous osteosarcoma V793 that originated in a 19-month-old female BALB/c mouse were cultured. They did not produce a C-type oncovirus as determined by extracellular reverse transcriptase assay and cytoplasmic immunofluorescence. After cocultivation with Balb/3T3 cells chronically infected with a murine leukemia virus (MuLV), a focus-forming principle that transformed 3T3 cells, secondary BALB/c mouse embryo and WAG/Rij rat embryo fibroblasts were rescued. The transformation could be inhibited by antiserum to MuLV.", "contents": "Rescue of a transforming virus from a spontaneous nonproducing osteosarcoma in BALB/c mice. Cells from spontaneous osteosarcoma V793 that originated in a 19-month-old female BALB/c mouse were cultured. They did not produce a C-type oncovirus as determined by extracellular reverse transcriptase assay and cytoplasmic immunofluorescence. After cocultivation with Balb/3T3 cells chronically infected with a murine leukemia virus (MuLV), a focus-forming principle that transformed 3T3 cells, secondary BALB/c mouse embryo and WAG/Rij rat embryo fibroblasts were rescued. The transformation could be inhibited by antiserum to MuLV."}
{"id": "PMID:202719", "title": "Glucan: attempts to demonstrate therapeutic activity against five syngeneic tumors in guinea pigs and mice.", "content": "Animals with established syngeneic tumor transplants were treated with glucan to study the therapeutic potential of this agent under well-defined experimental conditions. The tumors used were a guinea pig hepatoma, 2 murine fibrosarcomas, a murine melanoma, and a murine adenocarcinoma. All tumors were syngeneic to the host. Living BCG, administered directly into guinea pig tumors, cured all animals, whereas glucan, administered under the same conditions, had no significant antitumor activity. Neither BCG nor glucan, when administered iv, was active against the guinea pig hepatoma. An emulsion prepared with endotoxin, a fraction of mycobacteria related to cord factor, and mineral oil when administered intratumorally was also effective in treatment of line 10 tumor. A similar emulsion, in which glucan was substituted for endotoxin, was inactive, intralesional, ip, or iv administration of glucan was ineffective against the murine tumors. Previous reports of glucan-induced activity against a B16 murine melanoma were not confirmed. BCG was tested against the 2 murine fibrosarcomas and, when given either intratumorally or iv, was found to be effective against one of them.", "contents": "Glucan: attempts to demonstrate therapeutic activity against five syngeneic tumors in guinea pigs and mice. Animals with established syngeneic tumor transplants were treated with glucan to study the therapeutic potential of this agent under well-defined experimental conditions. The tumors used were a guinea pig hepatoma, 2 murine fibrosarcomas, a murine melanoma, and a murine adenocarcinoma. All tumors were syngeneic to the host. Living BCG, administered directly into guinea pig tumors, cured all animals, whereas glucan, administered under the same conditions, had no significant antitumor activity. Neither BCG nor glucan, when administered iv, was active against the guinea pig hepatoma. An emulsion prepared with endotoxin, a fraction of mycobacteria related to cord factor, and mineral oil when administered intratumorally was also effective in treatment of line 10 tumor. A similar emulsion, in which glucan was substituted for endotoxin, was inactive, intralesional, ip, or iv administration of glucan was ineffective against the murine tumors. Previous reports of glucan-induced activity against a B16 murine melanoma were not confirmed. BCG was tested against the 2 murine fibrosarcomas and, when given either intratumorally or iv, was found to be effective against one of them."}
{"id": "PMID:202720", "title": "Incidence, latency, and morphologic types of neoplasms induced by simian virus 40 inoculated intravenously into hamsters of three inbred strains and one outbred stock.", "content": "The incidence, latency, and morphologic types of neoplasms induced in hamsters of the three inbred strains LSH/SsLak, LHC/Lak, and MHA/SsLak, inocuated iv at 3 weeks of age with 10(7.5) median tissue culture infective dose (TCID50) of simian virus 40 (SV40). were determined and compared with those of the outbred stock LVG/Lak. Although the incidence and latency were approximately the same in hamsters of the three inbred strains, hamsters of the outbred stock exhibited almost complete resistance to tumor induction under identical experimental conditions. The morphologic types of neoplasms, i.e., lymphocytic leukemia, reticulum cell sarcoma, osteogenic sarcoma, and anaplastic sarcoma, induced in inbred hamsters were similar to those induced in outbred hamsters inoculated iv with 10(8.5) TCID50 SV40. The lymphocytic leukemias that developed in the 2 LSH/SsLak inbred hamsters were established as tumor transplants in vivo and as permanent cell lines in vitro.", "contents": "Incidence, latency, and morphologic types of neoplasms induced by simian virus 40 inoculated intravenously into hamsters of three inbred strains and one outbred stock. The incidence, latency, and morphologic types of neoplasms induced in hamsters of the three inbred strains LSH/SsLak, LHC/Lak, and MHA/SsLak, inocuated iv at 3 weeks of age with 10(7.5) median tissue culture infective dose (TCID50) of simian virus 40 (SV40). were determined and compared with those of the outbred stock LVG/Lak. Although the incidence and latency were approximately the same in hamsters of the three inbred strains, hamsters of the outbred stock exhibited almost complete resistance to tumor induction under identical experimental conditions. The morphologic types of neoplasms, i.e., lymphocytic leukemia, reticulum cell sarcoma, osteogenic sarcoma, and anaplastic sarcoma, induced in inbred hamsters were similar to those induced in outbred hamsters inoculated iv with 10(8.5) TCID50 SV40. The lymphocytic leukemias that developed in the 2 LSH/SsLak inbred hamsters were established as tumor transplants in vivo and as permanent cell lines in vitro."}
{"id": "PMID:202721", "title": "Oncogenicity of murine mammary tumor virus produced in tissue culture: brief communication.", "content": "Murine mammary tumor virus (MuMTV), produced from a glucocorticoid-stimulated C3H mouse mammary adenocarcinoma cell line, was free of murine leukemia virus and oncogenic for weanling BALB/c mice. Adenocarcinomas were induced by MuMTV as early as 136 days post inoculation and with as low as 5 X 10(3) virus particles/mouse. Tumor incidence did not correlate directly with virus dose; rather, it was low at higher MuMTV concentrations (1.2 X 10(8) particles/mouse), reached and optimum at 1.3 X 10(5) particles/mouse, and decreased with virus dilution.", "contents": "Oncogenicity of murine mammary tumor virus produced in tissue culture: brief communication. Murine mammary tumor virus (MuMTV), produced from a glucocorticoid-stimulated C3H mouse mammary adenocarcinoma cell line, was free of murine leukemia virus and oncogenic for weanling BALB/c mice. Adenocarcinomas were induced by MuMTV as early as 136 days post inoculation and with as low as 5 X 10(3) virus particles/mouse. Tumor incidence did not correlate directly with virus dose; rather, it was low at higher MuMTV concentrations (1.2 X 10(8) particles/mouse), reached and optimum at 1.3 X 10(5) particles/mouse, and decreased with virus dilution."}
{"id": "PMID:202722", "title": "Toxicity of vinylidene chloride in mice and rats and its alterations by various treatments.", "content": "The toxicity of vinylidene chloride (VDC) was studied in mice and rats exposed to various concentrations of the vapors for 23 hr/day. In addition, the ability of various compounds to alter parameters of toxicity was evaluated. Mice were more sensitive than rats to the lethal, hepatotoxic, and renal toxic effects of VDC. Disulfiram protected mice from these toxic effects of inhaled VDC and reduced the levels of covalently bound radioactivity in the liver and kidney after the ip administration of [14C] VDC. Diethyldithiocarbamate and thiram also protected mice from the acute lethal effects of VDC.", "contents": "Toxicity of vinylidene chloride in mice and rats and its alterations by various treatments. The toxicity of vinylidene chloride (VDC) was studied in mice and rats exposed to various concentrations of the vapors for 23 hr/day. In addition, the ability of various compounds to alter parameters of toxicity was evaluated. Mice were more sensitive than rats to the lethal, hepatotoxic, and renal toxic effects of VDC. Disulfiram protected mice from these toxic effects of inhaled VDC and reduced the levels of covalently bound radioactivity in the liver and kidney after the ip administration of [14C] VDC. Diethyldithiocarbamate and thiram also protected mice from the acute lethal effects of VDC."}
{"id": "PMID:202723", "title": "Theoretical considerations of local neuron circuits and their triadic synaptic arrangements (TSA) in subcortical sensory nuclei.", "content": "Certain sequential models of the so-called synaptic triadic arrangements (TSA) occurring in sensory nuclei are analyzed. The considerations are addressed mainly to the lateral geniculate body. The model is based on the assumption that the neurons establishing these triads consist of conditionally coupled decision-making subunits. It might be concluded that this and similar arrangements could play a role in the discrimination between stationary and moving retinal inputs and in the detection of temporal correlations in certain input channels.", "contents": "Theoretical considerations of local neuron circuits and their triadic synaptic arrangements (TSA) in subcortical sensory nuclei. Certain sequential models of the so-called synaptic triadic arrangements (TSA) occurring in sensory nuclei are analyzed. The considerations are addressed mainly to the lateral geniculate body. The model is based on the assumption that the neurons establishing these triads consist of conditionally coupled decision-making subunits. It might be concluded that this and similar arrangements could play a role in the discrimination between stationary and moving retinal inputs and in the detection of temporal correlations in certain input channels."}
{"id": "PMID:202724", "title": "Neurochemical effects of cocaine following acute and repeated injection.", "content": "Following repeated injection in the rat, cocaine decreased the concentration of serotonin in the septum-caudate and increased the metabolism of hypothalamic norepinephrine and also striatal dopamine to a lesser extent. Furthermore, cocaine significantly decreased the activity of the rate-limiting enzyme, tryptophan hydroxylase. In a comparative study d-amphetamine and methylphenidate were found to exert an effect opposite to cocaine in the activation of tryptophan hydroxylase. These findings indicate that cocaine may lower central serotonin function by decreasing its availability for neural transmission. This could account for the stimulation of locomotor activity observed after cocaine administration.", "contents": "Neurochemical effects of cocaine following acute and repeated injection. Following repeated injection in the rat, cocaine decreased the concentration of serotonin in the septum-caudate and increased the metabolism of hypothalamic norepinephrine and also striatal dopamine to a lesser extent. Furthermore, cocaine significantly decreased the activity of the rate-limiting enzyme, tryptophan hydroxylase. In a comparative study d-amphetamine and methylphenidate were found to exert an effect opposite to cocaine in the activation of tryptophan hydroxylase. These findings indicate that cocaine may lower central serotonin function by decreasing its availability for neural transmission. This could account for the stimulation of locomotor activity observed after cocaine administration."}
{"id": "PMID:202725", "title": "The effect of antibiotics, primary and secondary closure on clostridial contaminated open fracture wounds in rats.", "content": "In a study of experimentally induced open tibial or femoral fractures in rats, after either closing or leaving the wounds open, the animals were given: no antibiotic, cephalothin (Keflin), or penicillin. The rats with wounds closed primarily and receiving no antibiotics had the highest mortality rate (11 of 25) from experimentally produced clostridial myonecrosis. The lowest overall mortality rate (5 of 99) was found in the penicillin-treated groups. The higher mortality rate in the femur fracture groups was probably because of the large muscle mass of the thigh. The importance of ideal anaerobic conditions for producing experimental clostridial myonecrosis is emphasized.", "contents": "The effect of antibiotics, primary and secondary closure on clostridial contaminated open fracture wounds in rats. In a study of experimentally induced open tibial or femoral fractures in rats, after either closing or leaving the wounds open, the animals were given: no antibiotic, cephalothin (Keflin), or penicillin. The rats with wounds closed primarily and receiving no antibiotics had the highest mortality rate (11 of 25) from experimentally produced clostridial myonecrosis. The lowest overall mortality rate (5 of 99) was found in the penicillin-treated groups. The higher mortality rate in the femur fracture groups was probably because of the large muscle mass of the thigh. The importance of ideal anaerobic conditions for producing experimental clostridial myonecrosis is emphasized."}
{"id": "PMID:202728", "title": "Some adenovirus DNA is associated with the DNA of permissive cells during productive or restricted growth.", "content": "We have investigated the association of viral DNA with cell DNA in chicken embryo kidney (CEK) cells productively infected with chicken embryo lethal orphan (CELO) virus and in human (HEK) cells infected with mutants ts36 and ts125 of human adenovirus type 5 under permissive and restrictive conditions. Cell and viral DNA molecules were separated after CELO virus infection of CEK cells by alkaline sucrose gradient centrifugation, network formation, and CsCl density gradient centrifugation, methods that rely on different properties of the DNA. The cell DNA was then tested for viral sequences by DNA reannealing kinetics. Between 500 and 1,000 viral genome equivalents per cell were found at 36 h postinfection associated with cell DNA purified by each method. These values greatly exceeded the amount of free viral DNA found contaminating cell DNA prepared by the same methods from uninfected cells to which CELO virus DNA had been added. Quantitative agreement in the amounts of viral DNA found associated with cell DNA purified by these different methods suggests that CELO virus DNA is integrated into chick cell DNA during lytic infection. Similar experiments in HEK cells using mutants ts36 and ts125 of adenovirus type 5 at both restrictive and permissive temperatures showed that the same proportion of viral DNA is associated with cell DNA in the absence of viral DNA replication, and this suggests that the difference in the frequency with which cells are transformed by these mutants is not due to a difference in the frequency integration.", "contents": "Some adenovirus DNA is associated with the DNA of permissive cells during productive or restricted growth. We have investigated the association of viral DNA with cell DNA in chicken embryo kidney (CEK) cells productively infected with chicken embryo lethal orphan (CELO) virus and in human (HEK) cells infected with mutants ts36 and ts125 of human adenovirus type 5 under permissive and restrictive conditions. Cell and viral DNA molecules were separated after CELO virus infection of CEK cells by alkaline sucrose gradient centrifugation, network formation, and CsCl density gradient centrifugation, methods that rely on different properties of the DNA. The cell DNA was then tested for viral sequences by DNA reannealing kinetics. Between 500 and 1,000 viral genome equivalents per cell were found at 36 h postinfection associated with cell DNA purified by each method. These values greatly exceeded the amount of free viral DNA found contaminating cell DNA prepared by the same methods from uninfected cells to which CELO virus DNA had been added. Quantitative agreement in the amounts of viral DNA found associated with cell DNA purified by these different methods suggests that CELO virus DNA is integrated into chick cell DNA during lytic infection. Similar experiments in HEK cells using mutants ts36 and ts125 of adenovirus type 5 at both restrictive and permissive temperatures showed that the same proportion of viral DNA is associated with cell DNA in the absence of viral DNA replication, and this suggests that the difference in the frequency with which cells are transformed by these mutants is not due to a difference in the frequency integration."}
{"id": "PMID:202729", "title": "Virus-specific DNA in the cytoplasm of avian sarcoma virus-infected cells is a precursor to covalently closed circular viral DNA in the nucleus.", "content": "Three principal forms of viral DNA have been identified in cells infected with avian sarcoma virus: (i) a linear duplex molecule synthesized in the cytoplasm, (ii) a covalently closed circular molecule found in the nucleus, and (iii) proviral DNA covalently linked to high-molecular-weight cell DNA. To define precursor product relationships among these forms of viral DNA, we performed pulsechase experiments using 5-bromodeoxyuridine to label by density the linear species of viral DNA in the cytoplasm during the first 4 h after infection. After a 4-to 8-h chase with thymidine, a portion of the density-labeled viral DNA was transported to the nucleus and converted to a covalently closed circular form. We conclude that linear viral DNA, synthesized in the cytoplasm, is the precursor to closed circular DNA observed in the nucleus.", "contents": "Virus-specific DNA in the cytoplasm of avian sarcoma virus-infected cells is a precursor to covalently closed circular viral DNA in the nucleus. Three principal forms of viral DNA have been identified in cells infected with avian sarcoma virus: (i) a linear duplex molecule synthesized in the cytoplasm, (ii) a covalently closed circular molecule found in the nucleus, and (iii) proviral DNA covalently linked to high-molecular-weight cell DNA. To define precursor product relationships among these forms of viral DNA, we performed pulsechase experiments using 5-bromodeoxyuridine to label by density the linear species of viral DNA in the cytoplasm during the first 4 h after infection. After a 4-to 8-h chase with thymidine, a portion of the density-labeled viral DNA was transported to the nucleus and converted to a covalently closed circular form. We conclude that linear viral DNA, synthesized in the cytoplasm, is the precursor to closed circular DNA observed in the nucleus."}
{"id": "PMID:202730", "title": "Identification of a 30S RNA with properties of a defective type C virus in murine cells.", "content": "A novel species of 30S RNA has been detected in a variety of mouse cell lines. The 30S RNA is specifically packaged by helper-independent type C viruses propagated in such cells. Nucleic acid hybridization detects no homology between the 30SRNA and the genomic RNA of helper-independent mouse type C viruses. The properties of the 30S RNA suggest that it is a defective endogenous mouse type C virus and that it is analogous to a previously described class of defective endogenous rat type C virus, which has been shown previously to be the progenitor of Kirsten and Harvey murine sarcoma viruses.", "contents": "Identification of a 30S RNA with properties of a defective type C virus in murine cells. A novel species of 30S RNA has been detected in a variety of mouse cell lines. The 30S RNA is specifically packaged by helper-independent type C viruses propagated in such cells. Nucleic acid hybridization detects no homology between the 30SRNA and the genomic RNA of helper-independent mouse type C viruses. The properties of the 30S RNA suggest that it is a defective endogenous mouse type C virus and that it is analogous to a previously described class of defective endogenous rat type C virus, which has been shown previously to be the progenitor of Kirsten and Harvey murine sarcoma viruses."}
{"id": "PMID:202731", "title": "Effect of cordycepin triphosphate on in vitro RNA synthesis by picornavirus polymerase complexes.", "content": "Cordycepin triphosphate inhibited in vitro [3H]GMP incorporation by pricornavirus-specific polymerase complexes isolated from infected HeLa cells. The inhibition of [3H]GMP incorporation could be reversed with ATP added to the reaction mixture along with the inhibitor, but not with GTP so added or with ATP added 10 min after the inhibitor. Products synthesized in vitro in the presence of cordycepin triphosphate lacked full-length single-stranded viral RNA. These results support RNA chain termination by specific competition with ATP as the mechanism of inhibition of picornavirus-specific RNA synthesis by cordycepin triphosphate.", "contents": "Effect of cordycepin triphosphate on in vitro RNA synthesis by picornavirus polymerase complexes. Cordycepin triphosphate inhibited in vitro [3H]GMP incorporation by pricornavirus-specific polymerase complexes isolated from infected HeLa cells. The inhibition of [3H]GMP incorporation could be reversed with ATP added to the reaction mixture along with the inhibitor, but not with GTP so added or with ATP added 10 min after the inhibitor. Products synthesized in vitro in the presence of cordycepin triphosphate lacked full-length single-stranded viral RNA. These results support RNA chain termination by specific competition with ATP as the mechanism of inhibition of picornavirus-specific RNA synthesis by cordycepin triphosphate."}
{"id": "PMID:202732", "title": "Cytofluorometry of lymphocytes infected with Epstein-Barr virus: effect of phosphonoacetic acid on nucleic acid.", "content": "DNA synthesis in Epstein-Barr virus (EBV)-infected lymphocytes was inhibited by phosphonoacetic acid (PAA) as measured by [3H]thymidine incorporation. PAA, at a concentration of 200 microgram/ml, inhibited [3H]thymidine incorporation by human umbilical cord lymphocytes infected with EBV strain P94 but had little effect on DNA synthesis in mitogen-stimulated cells. Transformed cell lines did not develop from infected cord cell cultures treated with 100 microgram of PAA per ml. Cytofluorometric analysis showed marked increases in cellular nucleic acid content (RNA plus DNA) as early as 9 days after infection of cord cells in the absence of PAA and before significant enhancement of [3H]thymidine incorporation became apparent. Moreover, EBV led to increases in cellular nucleic acid even when 200 microgram of PAA per ml was added to cell cultures before infection. The apparent discrepancy between results obtained by [3H]thymidine incorporation and cytofluorometry is explained either by significant inhibition of cellular DNA polymerases by PAA or by a block at the G2 + M phase of the cell cycle. The data suggest that EBV initiates alterations in cellular nucleic acid synthesis or cell division without prior replication of viral DNA by virus-induced DNA polymerases.", "contents": "Cytofluorometry of lymphocytes infected with Epstein-Barr virus: effect of phosphonoacetic acid on nucleic acid. DNA synthesis in Epstein-Barr virus (EBV)-infected lymphocytes was inhibited by phosphonoacetic acid (PAA) as measured by [3H]thymidine incorporation. PAA, at a concentration of 200 microgram/ml, inhibited [3H]thymidine incorporation by human umbilical cord lymphocytes infected with EBV strain P94 but had little effect on DNA synthesis in mitogen-stimulated cells. Transformed cell lines did not develop from infected cord cell cultures treated with 100 microgram of PAA per ml. Cytofluorometric analysis showed marked increases in cellular nucleic acid content (RNA plus DNA) as early as 9 days after infection of cord cells in the absence of PAA and before significant enhancement of [3H]thymidine incorporation became apparent. Moreover, EBV led to increases in cellular nucleic acid even when 200 microgram of PAA per ml was added to cell cultures before infection. The apparent discrepancy between results obtained by [3H]thymidine incorporation and cytofluorometry is explained either by significant inhibition of cellular DNA polymerases by PAA or by a block at the G2 + M phase of the cell cycle. The data suggest that EBV initiates alterations in cellular nucleic acid synthesis or cell division without prior replication of viral DNA by virus-induced DNA polymerases."}
{"id": "PMID:202733", "title": "Glucocorticoids induce focus formation and increase sarcoma viral expression in a mink cell line that contains a murine sarcoma viral genome.", "content": "Dexamethasone (3 X 10(-10) to 3 X 10(-6) M) induced foci of morphologically transformed cells in a small proportion of a mink cell line that contains the Moloney murine sarcoma viral genome (S+L-). The induction was glucocorticoid specific, since other steroids with glucocorticoid activity (prednisolone, cortisol, and aldosterone) induced foci with an efficiency that paralleled their glucocorticoid activity, and steroids lacking glucocorticoid activity (17B-estradiol, testosterone, and progesterone) failed to induce foci. Viral antigen, as measured by specific immunofluorescence, was localized to the foci. The induction of foci by dexamethasone (3 X 10(-7)) was accompanied by an approximately 10-fold increase in intracellular Moloney murine sarcoma virus-specific RNA and viral p30 antigen. Removal of dexamethasone was followed by the disappearance of foci and a decrease in viral RNA and p30. In this cell system, therefore, glucocorticoids can affect the intracellular levels of type C viral RNA and protein.", "contents": "Glucocorticoids induce focus formation and increase sarcoma viral expression in a mink cell line that contains a murine sarcoma viral genome. Dexamethasone (3 X 10(-10) to 3 X 10(-6) M) induced foci of morphologically transformed cells in a small proportion of a mink cell line that contains the Moloney murine sarcoma viral genome (S+L-). The induction was glucocorticoid specific, since other steroids with glucocorticoid activity (prednisolone, cortisol, and aldosterone) induced foci with an efficiency that paralleled their glucocorticoid activity, and steroids lacking glucocorticoid activity (17B-estradiol, testosterone, and progesterone) failed to induce foci. Viral antigen, as measured by specific immunofluorescence, was localized to the foci. The induction of foci by dexamethasone (3 X 10(-7)) was accompanied by an approximately 10-fold increase in intracellular Moloney murine sarcoma virus-specific RNA and viral p30 antigen. Removal of dexamethasone was followed by the disappearance of foci and a decrease in viral RNA and p30. In this cell system, therefore, glucocorticoids can affect the intracellular levels of type C viral RNA and protein."}
{"id": "PMID:202734", "title": "Comparison of nuclease digestion of polyoma virus nucleoprotein complex and mouse chromatin.", "content": "We digested polyoma virus nucleoprotein complex, isolated from disrupted virions, with micrococcal nuclease and DNase I. The results were compared with digestions of chromatin from mouse nuclei. The nucleosome \"core\" structures were similar, but the spacing of the nucleosomes in the isolated polymoma nucleoprotein complexes was irregular, whereas in mouse chromatin it was regular. The average nucleosome repeat length in each case was 190 to 200 base pairs. This figure suggests that, unless there are substantial stretches of free DNA, the polyoma nucleoprotein complex contains about 26 nucleosomes. The commonly used method of preparing the nucleoprotein complex by disruption of virions at pH 10.2 may lead to significant damage to the structure. Such damage may be more clearly revealed by the susceptibility of the DNA to nuclease digestion than by the usual criteria of sedimentation velocity and buoyant density.", "contents": "Comparison of nuclease digestion of polyoma virus nucleoprotein complex and mouse chromatin. We digested polyoma virus nucleoprotein complex, isolated from disrupted virions, with micrococcal nuclease and DNase I. The results were compared with digestions of chromatin from mouse nuclei. The nucleosome \"core\" structures were similar, but the spacing of the nucleosomes in the isolated polymoma nucleoprotein complexes was irregular, whereas in mouse chromatin it was regular. The average nucleosome repeat length in each case was 190 to 200 base pairs. This figure suggests that, unless there are substantial stretches of free DNA, the polyoma nucleoprotein complex contains about 26 nucleosomes. The commonly used method of preparing the nucleoprotein complex by disruption of virions at pH 10.2 may lead to significant damage to the structure. Such damage may be more clearly revealed by the susceptibility of the DNA to nuclease digestion than by the usual criteria of sedimentation velocity and buoyant density."}
{"id": "PMID:202735", "title": "Electron microscope study of the base sequence homology between simian virus 40 and human papovavirus BK.", "content": "The base sequence homology between the genomes of simian virus 40 (SV40) and human papovavirus BK (BKV) was studied by the heteroduplex method of Ferguson and Davis (J. Mol. Biol. 94:135-149, 1975). When mounted for microscopy in 30% formamide (Tm-35 degrees C), BKV/SV40 heteroduplexes were an average of 92% double-stranded and contained only two small nonhomologous regions that mapped near the junctions between the early and late regions of the SV40 Genome. At higher formamide concentrations, the fraction of duplex DNA in the BKV/SV40 heteroduplexes decreased, indicating  significant base mismatching in the homologous regions. The strongest regions of homology were located in the late region.", "contents": "Electron microscope study of the base sequence homology between simian virus 40 and human papovavirus BK. The base sequence homology between the genomes of simian virus 40 (SV40) and human papovavirus BK (BKV) was studied by the heteroduplex method of Ferguson and Davis (J. Mol. Biol. 94:135-149, 1975). When mounted for microscopy in 30% formamide (Tm-35 degrees C), BKV/SV40 heteroduplexes were an average of 92% double-stranded and contained only two small nonhomologous regions that mapped near the junctions between the early and late regions of the SV40 Genome. At higher formamide concentrations, the fraction of duplex DNA in the BKV/SV40 heteroduplexes decreased, indicating  significant base mismatching in the homologous regions. The strongest regions of homology were located in the late region."}
{"id": "PMID:202736", "title": "Host function-dependent induction of defective interfering particles of vesicular stomatitis virus.", "content": "Suppression of host cell function by treatment with actinomycin D prior to infection prevented the induction of defective interfering particles of vesicular stomatitis virus, which had been cloned and propagated in cell pretreated with actinomycin D. Replication of defective interfering particles already present in an infecting virus stock, however, was not affected by pretreatment of cells with actinomycin D. Thus, the induction, but not the replication, of defective interfering particles appears to be a host cell function-dependent phenomenon. The implications of this phenomenon for host defense mechanisms against virus infections are discussed.", "contents": "Host function-dependent induction of defective interfering particles of vesicular stomatitis virus. Suppression of host cell function by treatment with actinomycin D prior to infection prevented the induction of defective interfering particles of vesicular stomatitis virus, which had been cloned and propagated in cell pretreated with actinomycin D. Replication of defective interfering particles already present in an infecting virus stock, however, was not affected by pretreatment of cells with actinomycin D. Thus, the induction, but not the replication, of defective interfering particles appears to be a host cell function-dependent phenomenon. The implications of this phenomenon for host defense mechanisms against virus infections are discussed."}
{"id": "PMID:202737", "title": "Polyacrylamide gel electrophoresis of visna virus polypeptides isolated by agarose gel chromatography.", "content": "The proteins of visna are separated into nine major peaks by agarose gel chromatography in 6 M guanidine hydrochloride (GuHCl). The polypeptides in eack peak were isolated by acid precipitation and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The patterns of SDS-PAGE show that the excluded material from the GuHCl column contains an aggregate of 10 non-glycosylated polypeptides. It is shown that this aggregate represents virus substructures that are not completely solubilized by GuHCl. Two glycoproteins, gp175 and gp115, were isolated from the column eluate. The major glycoprotein gp115 was coeluted with P90, P68, and P61 in GuHCl 4. Each of the four major peaks (GuHCl 5 to 8) contains more than one nonglycosylated polypeptide. However, a small polypeptide, P12, can be isolated in a homogeneous form in the last peak, GuHCl 9. Analysis of the virus proteins (100 microgram) by SDS-PAGE shows that 20 radioactive bands can be recognized. During fractionation of the protein on agarose gel columns followed by analysis with SDS-PAGE, a number of minor polypeptides that were not detected before became clearly recognizable. Thus, the combined use of column chromatography and SDS-PAGE shows that visna virus is composed of 25 proteins.", "contents": "Polyacrylamide gel electrophoresis of visna virus polypeptides isolated by agarose gel chromatography. The proteins of visna are separated into nine major peaks by agarose gel chromatography in 6 M guanidine hydrochloride (GuHCl). The polypeptides in eack peak were isolated by acid precipitation and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The patterns of SDS-PAGE show that the excluded material from the GuHCl column contains an aggregate of 10 non-glycosylated polypeptides. It is shown that this aggregate represents virus substructures that are not completely solubilized by GuHCl. Two glycoproteins, gp175 and gp115, were isolated from the column eluate. The major glycoprotein gp115 was coeluted with P90, P68, and P61 in GuHCl 4. Each of the four major peaks (GuHCl 5 to 8) contains more than one nonglycosylated polypeptide. However, a small polypeptide, P12, can be isolated in a homogeneous form in the last peak, GuHCl 9. Analysis of the virus proteins (100 microgram) by SDS-PAGE shows that 20 radioactive bands can be recognized. During fractionation of the protein on agarose gel columns followed by analysis with SDS-PAGE, a number of minor polypeptides that were not detected before became clearly recognizable. Thus, the combined use of column chromatography and SDS-PAGE shows that visna virus is composed of 25 proteins."}
{"id": "PMID:202738", "title": "Physical map of the Kirsten sarcoma virus genome as determined by fingerprinting RNase T1-resistant oligonucleotides.", "content": "From analysis of the large RNase T1-resistant oligonucleotides of Kirsten sarcoma virus (Ki-SV), a physical map of the virus genome was deduced. Kirsten murine leukemia virus (Ki-MuLV) sequences were detected in T1 oligonucleotides closest to the 3' end of the viral RNA and extended approximately 1,000 nucleotides into the genome. The rat genetic sequences started at this point and extended all the way to the very 5' end of the RNA molecules, where a small stretch of Ki-MuLV sequence was detected. By comparison of the fingerprints of Ki-SV RNA and the RNA of the endogenous rat src genetic sequences, it was found that more than 50% of the T1 oligonucleotides were similar between Ki-SV and the endogenous rat src RNA, suggesting an identical primary nucleotide sequence in over 50% of the viral genomes. The results indicate that Ki-SV arose by recombination between the 5' and 3' ends of Ki-MuLV and a large portion of the homologous sequences of the endogenous rat src RNA.", "contents": "Physical map of the Kirsten sarcoma virus genome as determined by fingerprinting RNase T1-resistant oligonucleotides. From analysis of the large RNase T1-resistant oligonucleotides of Kirsten sarcoma virus (Ki-SV), a physical map of the virus genome was deduced. Kirsten murine leukemia virus (Ki-MuLV) sequences were detected in T1 oligonucleotides closest to the 3' end of the viral RNA and extended approximately 1,000 nucleotides into the genome. The rat genetic sequences started at this point and extended all the way to the very 5' end of the RNA molecules, where a small stretch of Ki-MuLV sequence was detected. By comparison of the fingerprints of Ki-SV RNA and the RNA of the endogenous rat src genetic sequences, it was found that more than 50% of the T1 oligonucleotides were similar between Ki-SV and the endogenous rat src RNA, suggesting an identical primary nucleotide sequence in over 50% of the viral genomes. The results indicate that Ki-SV arose by recombination between the 5' and 3' ends of Ki-MuLV and a large portion of the homologous sequences of the endogenous rat src RNA."}
{"id": "PMID:202739", "title": "DNA-binding proteins in the cytoplasm of vaccinia virus-infected mouse L-cells.", "content": "Mouse L cell fibroblasts were infected with vaccinia virus and labeled 2 to 3 h postinfection with [35S]methionine. Labeled proteins were fractionated on native and denatured DNA-cellulose columns and then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Twenty-four 90,000 to 12,500, were detected. VDP-12A (molecular weight, 29,750) had affinity for denatured but not native DNA, and its synthesis was dependent on viral DNA replication. VDP-20 (molecular weight, 41,000) bound very tightly to native and denatured DNA and was displaced only after boiling the protein-DNA-cellulose matrix in 1% sodium dodecyl sulfate. VDP-8,-11,-12,-13, -and-14 behaved electrophoretically like the polypeptide species previously shown to be present in DNA-protein complexes prepared from infected cells. The molecular weights of VDP-10 (50,000), VDP-11 (36,000), and VDP-8 (67,000) were similar to the polypeptide subunits of polyadenylate polymerase and phosphohydrolase I, enzymes purified from virions which have also been shown to have affinity for DNA.", "contents": "DNA-binding proteins in the cytoplasm of vaccinia virus-infected mouse L-cells. Mouse L cell fibroblasts were infected with vaccinia virus and labeled 2 to 3 h postinfection with [35S]methionine. Labeled proteins were fractionated on native and denatured DNA-cellulose columns and then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Twenty-four 90,000 to 12,500, were detected. VDP-12A (molecular weight, 29,750) had affinity for denatured but not native DNA, and its synthesis was dependent on viral DNA replication. VDP-20 (molecular weight, 41,000) bound very tightly to native and denatured DNA and was displaced only after boiling the protein-DNA-cellulose matrix in 1% sodium dodecyl sulfate. VDP-8,-11,-12,-13, -and-14 behaved electrophoretically like the polypeptide species previously shown to be present in DNA-protein complexes prepared from infected cells. The molecular weights of VDP-10 (50,000), VDP-11 (36,000), and VDP-8 (67,000) were similar to the polypeptide subunits of polyadenylate polymerase and phosphohydrolase I, enzymes purified from virions which have also been shown to have affinity for DNA."}
{"id": "PMID:202740", "title": "Endoribonuclease activity associated with animal RNA viruses.", "content": "A specific endoribonucleolytic activity was detected when detergent-lysed vesicular stomatitis of Sendai virus was incubated with the precursor to Escherichia coli tRNA Tyr. The cleavage products produced and the characteristics of the reaction were similar to those previously reported for human KB cell RNase NU. Like RNase NU, the virus-associated reaction generates 5'-hydroxyl and 3'-phosphate groups at the cleavage sites. At protein concentrations similar to those used to test vesicular stomatitis and Sendai viruses, virions of Sindbis virus and poliovirus also exhibited endoribonucleolytic activity, but reovirus, simian virus 40, and minute virus of mice did not. This endoribonuclease may be of physiological relevance to some of the viruses we tested.", "contents": "Endoribonuclease activity associated with animal RNA viruses. A specific endoribonucleolytic activity was detected when detergent-lysed vesicular stomatitis of Sendai virus was incubated with the precursor to Escherichia coli tRNA Tyr. The cleavage products produced and the characteristics of the reaction were similar to those previously reported for human KB cell RNase NU. Like RNase NU, the virus-associated reaction generates 5'-hydroxyl and 3'-phosphate groups at the cleavage sites. At protein concentrations similar to those used to test vesicular stomatitis and Sendai viruses, virions of Sindbis virus and poliovirus also exhibited endoribonucleolytic activity, but reovirus, simian virus 40, and minute virus of mice did not. This endoribonuclease may be of physiological relevance to some of the viruses we tested."}
{"id": "PMID:202741", "title": "Transcription of host-substituted simian virus 40 DNA in whole cells and extracts.", "content": "Viral transcriptional complexes were extracted from the nuclei of monkey kidney cells infected with wild-type simian virus 40 (SV40) or a variant strain containing a high proportion of host-substituted DNA molecules. The RNAs synthesized by these complexes in an in vitro system were analyzed for their content of SV40 and host sequences by a technique of sequential hybridization to plaque-purified and substituted viral DNAs. The relative labeling of the two types of sequences was commensurate with their proportion in the viral DNA (about 20% host). The substituted virus contains both reiterated and unique types of cellular sequences, and both kinds appeared to be transcribed. Transcripts of the substituted sequences formed a much smaller proportion of the virus related RNA recovered from intact infected cells, suggesting that host sequence transcripts are synthesized but rapidly degraded in the whole cell. The alternative, that transcription of these sequences is artificially enhanced in the in vitro system, cannot be rigorously excluded. We compared the self-annealing of viral RNAs from nuclear extracts of cells infected with wild-type and substituted viruses; transcripts labeled both in vivo and in vitro showed a two- to threefold-higher level of self-annealing in the case of the variant than in the case of wild type SV40.", "contents": "Transcription of host-substituted simian virus 40 DNA in whole cells and extracts. Viral transcriptional complexes were extracted from the nuclei of monkey kidney cells infected with wild-type simian virus 40 (SV40) or a variant strain containing a high proportion of host-substituted DNA molecules. The RNAs synthesized by these complexes in an in vitro system were analyzed for their content of SV40 and host sequences by a technique of sequential hybridization to plaque-purified and substituted viral DNAs. The relative labeling of the two types of sequences was commensurate with their proportion in the viral DNA (about 20% host). The substituted virus contains both reiterated and unique types of cellular sequences, and both kinds appeared to be transcribed. Transcripts of the substituted sequences formed a much smaller proportion of the virus related RNA recovered from intact infected cells, suggesting that host sequence transcripts are synthesized but rapidly degraded in the whole cell. The alternative, that transcription of these sequences is artificially enhanced in the in vitro system, cannot be rigorously excluded. We compared the self-annealing of viral RNAs from nuclear extracts of cells infected with wild-type and substituted viruses; transcripts labeled both in vivo and in vitro showed a two- to threefold-higher level of self-annealing in the case of the variant than in the case of wild type SV40."}
{"id": "PMID:202742", "title": "Binding and transcription of simian virus 40 DNA by DNA-dependent RNA polymerase from Escherichia coli.", "content": "Supercoiled simian virus 40 was transcribed more efficiently than nonsupercoiled DNA. The effect was increased from two- to fivefold by the addition of rifampin with triphosphates. The number and locations of polymerase binding sites with respect to Hin II-III restriction fragments were determined. The total number of binding sites was nine, as determined by UV difference spectroscopy. The locations of these binding sites were on the A, B, D, E, F, and G fragments, as determined by gel electrophoresis. The number of sites was the same for both supercoiled and relaxed or Hin II-III-digested DNA, and the point of saturation of supercoiled DNA by polymerase remained the same with increasing concentrations of rifampin from 0 to 8 microgram/ml.", "contents": "Binding and transcription of simian virus 40 DNA by DNA-dependent RNA polymerase from Escherichia coli. Supercoiled simian virus 40 was transcribed more efficiently than nonsupercoiled DNA. The effect was increased from two- to fivefold by the addition of rifampin with triphosphates. The number and locations of polymerase binding sites with respect to Hin II-III restriction fragments were determined. The total number of binding sites was nine, as determined by UV difference spectroscopy. The locations of these binding sites were on the A, B, D, E, F, and G fragments, as determined by gel electrophoresis. The number of sites was the same for both supercoiled and relaxed or Hin II-III-digested DNA, and the point of saturation of supercoiled DNA by polymerase remained the same with increasing concentrations of rifampin from 0 to 8 microgram/ml."}
{"id": "PMID:202743", "title": "Effect of chemical modification of supercoiled simian virus 40 DNA on the rate of in vitro transcription.", "content": "Superhelical simian virus 40 FI DNA could be modified with the single-strand-specific reagent N-cyclohexyl-N'-beta-(4-methylmorpholinium)ethylcarbodiimide (CMC). A limited reaction, of less than 2% of the base pairs, resulted in almost total inhibition of in vitro transcription by DNA-dependent RNA polymerase from Escherichia coli. This effect was shown to be due to DNA modification and not to inhibition of polymerase activity by the reagent. Inhibition of enzyme activity occurred if the contaminating reagent was not absorbed with another protein before polymerase addition. No inhibition was observed when DNA and polymerase were incubated together to allow the formation of pre-initiation complexes before CMC was added. Studies of template saturation with polymerase showed that the inhibition of transcription by DNA modification was due to a loss of binding ability of the enzyme to the reacted, supercoiled DNA when reaction times of less than 2 h were used.", "contents": "Effect of chemical modification of supercoiled simian virus 40 DNA on the rate of in vitro transcription. Superhelical simian virus 40 FI DNA could be modified with the single-strand-specific reagent N-cyclohexyl-N'-beta-(4-methylmorpholinium)ethylcarbodiimide (CMC). A limited reaction, of less than 2% of the base pairs, resulted in almost total inhibition of in vitro transcription by DNA-dependent RNA polymerase from Escherichia coli. This effect was shown to be due to DNA modification and not to inhibition of polymerase activity by the reagent. Inhibition of enzyme activity occurred if the contaminating reagent was not absorbed with another protein before polymerase addition. No inhibition was observed when DNA and polymerase were incubated together to allow the formation of pre-initiation complexes before CMC was added. Studies of template saturation with polymerase showed that the inhibition of transcription by DNA modification was due to a loss of binding ability of the enzyme to the reacted, supercoiled DNA when reaction times of less than 2 h were used."}
{"id": "PMID:202744", "title": "Presence of human chromosome 21 alone is sufficient for hybrid cell sensitivity to human interferon.", "content": "Human/mouse somatic cell hybrids with chromosome 21 as the only detectable human genetic material were sensitive to both human leukocyte and fibroblast interferons. The presence of additional human chromosomes decreased the amount of interferon needed to attain a given level of virus resistance. Decreased cytopathic effects, decreased virus yields, and the appearance of a specific phosphorylated protein associated with interferon treatment were all observed in hybrids maintaining only human chromosome 21. The phosphorylated protein found in extracts of these human interferon-treated hybrid cells was of mouse origin.", "contents": "Presence of human chromosome 21 alone is sufficient for hybrid cell sensitivity to human interferon. Human/mouse somatic cell hybrids with chromosome 21 as the only detectable human genetic material were sensitive to both human leukocyte and fibroblast interferons. The presence of additional human chromosomes decreased the amount of interferon needed to attain a given level of virus resistance. Decreased cytopathic effects, decreased virus yields, and the appearance of a specific phosphorylated protein associated with interferon treatment were all observed in hybrids maintaining only human chromosome 21. The phosphorylated protein found in extracts of these human interferon-treated hybrid cells was of mouse origin."}
{"id": "PMID:202745", "title": "Polyoma virus-human cell interactions: persistence of T-antigen in two cell lines with and without transformation.", "content": "The interaction of polyoma virus and human cells was investigated. Abortive infection as evidenced by the synthesis of T-antigen was observed in normal fibroblast and abnormal (transformed) cells but not in normal epithelial cells. A high percentage of simian virus 40-transformed WI-18 Va2 and spontaneously transformed BE skin cells produced T-antigen after high-multiplicity infection, but most of the cells rapidly lost antigen-producing capacity upon cell passage, and the cultures became negative by passage 3. All fibroblast cells displayed varying degrees of susceptibility to infection, but most of the cell lines became negative for T-antigen except for two. In one, T-antigen persisted in a small percentage of the cells throughout the lifetime of the culture, without cellular transformation occurring. In the other, the entire culture became morphologically transformed and eventually consisted of 100% T-antigen-positive cells. This is the first time that normal diploid human fibroblast cells have been transformed by polyoma virus.", "contents": "Polyoma virus-human cell interactions: persistence of T-antigen in two cell lines with and without transformation. The interaction of polyoma virus and human cells was investigated. Abortive infection as evidenced by the synthesis of T-antigen was observed in normal fibroblast and abnormal (transformed) cells but not in normal epithelial cells. A high percentage of simian virus 40-transformed WI-18 Va2 and spontaneously transformed BE skin cells produced T-antigen after high-multiplicity infection, but most of the cells rapidly lost antigen-producing capacity upon cell passage, and the cultures became negative by passage 3. All fibroblast cells displayed varying degrees of susceptibility to infection, but most of the cell lines became negative for T-antigen except for two. In one, T-antigen persisted in a small percentage of the cells throughout the lifetime of the culture, without cellular transformation occurring. In the other, the entire culture became morphologically transformed and eventually consisted of 100% T-antigen-positive cells. This is the first time that normal diploid human fibroblast cells have been transformed by polyoma virus."}
{"id": "PMID:202746", "title": "Comparison of two viable variants of simian virus 40.", "content": "The DNAs of two viable strains of simian virus 40, 776 and 777, have been compared by using restriction endonucleases. Differences between the two strains were detected at five separate points on the simian virus 40 genome. One of these differences, in the region of DNA coding for the major viral coat protein, was confirmed by tryptic peptide analysis of coat proteins from the two strains. Some physiological differences between the two strains were examined and can, in general, be explained by differences observed between the DNAs of the two strains. In addition, defective variants derived from strain 777 interfere more efficiently with the replication of strain 777 than with the replication of strain 776.", "contents": "Comparison of two viable variants of simian virus 40. The DNAs of two viable strains of simian virus 40, 776 and 777, have been compared by using restriction endonucleases. Differences between the two strains were detected at five separate points on the simian virus 40 genome. One of these differences, in the region of DNA coding for the major viral coat protein, was confirmed by tryptic peptide analysis of coat proteins from the two strains. Some physiological differences between the two strains were examined and can, in general, be explained by differences observed between the DNAs of the two strains. In addition, defective variants derived from strain 777 interfere more efficiently with the replication of strain 777 than with the replication of strain 776."}
{"id": "PMID:202747", "title": "Herpesvirus ateles DNA and its homology with Herpesvirus saimiri nucleic acid.", "content": "Analysis of the structural organization of Herpesvirus ateles DNA shows that two types of viral DNA molecules are encapsidated in virions: (i) M-genomes, which contain 74% light sequences (L-DNA, 38% guanine plus cytosine) and 26% highly repetitive heavy sequences (H-DNA, 75% guanine plus cytosine), and (ii) defective H-genomes, which consist exclusively of repetitive H-DNA. The structure of M-genomes from H. ateles consists of an L-DNA region of about 70 x 10(6) daltons inserted between H-DNA termini of variable length. M-genomes with a shorter H-DNA region at one end of the molecule have a long stretch of H-DNA at the other end, resulting in a total molecular weight of 89.8 +/- 8.5 x 10(6). Thus it resembles the structure of M-genomes of H. saimiri. H-DNA of the two independent H. ateles isolates, strains 810 and 73, reveals different patterns after cleavage with restriction endonuclease Sma I. H-DNA of H. ateles 810 appears to consist of identical tandem repeat units with a molecular weight of 1,035,000; the H-DNA repeat unit of strain 73 is shorter (930,000 molecular weight). Corresponding DNA sequences of the two H. ateles strains (810 and 73) are completely homologous in cross-hybridizations. However, a discrete nucleotide sequence divergence between these virus strains is detected by measuring melting temperatures (T(m)) of DNA hybrid molecules. Some homology exists between H. ateles and H. saimiri DNA. Hybridization of L-DNA from H. ateles with L-DNA from H. saimiri shows about a 35% homology between the respective L-DNA sequences; the resulting heteroduplex molecules show a decrease of T(m) by 13.5 degrees C, corresponding to about a 9% mismatching in cross-hybridizing parts of L-regions. Very little homology is found between H-DNA of H. ateles and H. saimiri.", "contents": "Herpesvirus ateles DNA and its homology with Herpesvirus saimiri nucleic acid. Analysis of the structural organization of Herpesvirus ateles DNA shows that two types of viral DNA molecules are encapsidated in virions: (i) M-genomes, which contain 74% light sequences (L-DNA, 38% guanine plus cytosine) and 26% highly repetitive heavy sequences (H-DNA, 75% guanine plus cytosine), and (ii) defective H-genomes, which consist exclusively of repetitive H-DNA. The structure of M-genomes from H. ateles consists of an L-DNA region of about 70 x 10(6) daltons inserted between H-DNA termini of variable length. M-genomes with a shorter H-DNA region at one end of the molecule have a long stretch of H-DNA at the other end, resulting in a total molecular weight of 89.8 +/- 8.5 x 10(6). Thus it resembles the structure of M-genomes of H. saimiri. H-DNA of the two independent H. ateles isolates, strains 810 and 73, reveals different patterns after cleavage with restriction endonuclease Sma I. H-DNA of H. ateles 810 appears to consist of identical tandem repeat units with a molecular weight of 1,035,000; the H-DNA repeat unit of strain 73 is shorter (930,000 molecular weight). Corresponding DNA sequences of the two H. ateles strains (810 and 73) are completely homologous in cross-hybridizations. However, a discrete nucleotide sequence divergence between these virus strains is detected by measuring melting temperatures (T(m)) of DNA hybrid molecules. Some homology exists between H. ateles and H. saimiri DNA. Hybridization of L-DNA from H. ateles with L-DNA from H. saimiri shows about a 35% homology between the respective L-DNA sequences; the resulting heteroduplex molecules show a decrease of T(m) by 13.5 degrees C, corresponding to about a 9% mismatching in cross-hybridizing parts of L-regions. Very little homology is found between H-DNA of H. ateles and H. saimiri."}
{"id": "PMID:202748", "title": "Synthesis and processing of precursor polypeptides to murine mammary tumor virus structural proteins.", "content": "Biosynthesis of murine mammary tumor virus (MuMTV) proteins was studied in the chronically MuMTV-infected epithelial cell line MuMT-73 by using monospecific antisera to the major MuMTV core protein p27 and the major envelope glycoprotein gp47. In pulse-labeling experiments using [35S]methionine, monospecific antisera to p27 precipitated a 75,000-molecular-weight protein as the major intracellular component. Analysis of the same cellular extracts with monospecific antisera to gp47 revealed that the gp47 precursor was a 70,000-dalton protein. After chase periods, there was a loss of label from the precursors and a concomitant increase of labeled extracellular mature viral proteins. The glycoprotein precursor incorporated labeled glucosamine and seemed to be processed more rapidly than the p27 precursor. Considerable amounts of apparently nonvirion-associated gp47 and glycoprotein precursor could be detected in the extracellular culture fluid.", "contents": "Synthesis and processing of precursor polypeptides to murine mammary tumor virus structural proteins. Biosynthesis of murine mammary tumor virus (MuMTV) proteins was studied in the chronically MuMTV-infected epithelial cell line MuMT-73 by using monospecific antisera to the major MuMTV core protein p27 and the major envelope glycoprotein gp47. In pulse-labeling experiments using [35S]methionine, monospecific antisera to p27 precipitated a 75,000-molecular-weight protein as the major intracellular component. Analysis of the same cellular extracts with monospecific antisera to gp47 revealed that the gp47 precursor was a 70,000-dalton protein. After chase periods, there was a loss of label from the precursors and a concomitant increase of labeled extracellular mature viral proteins. The glycoprotein precursor incorporated labeled glucosamine and seemed to be processed more rapidly than the p27 precursor. Considerable amounts of apparently nonvirion-associated gp47 and glycoprotein precursor could be detected in the extracellular culture fluid."}
{"id": "PMID:202749", "title": "Structure of 50 to 70S RNA from Moloney sarcoma viruses.", "content": "The 50 to 70S RNAs of two clonal isolates of defective Moloney sarcoma-leukemia helper virus complex were analyzed by gel electrophoresis and electron microscopy. The RNAs extracted from both clone 3 and clone 124-5R of Moloney sarcoma-leukemia virus complex contained some large monomer subunits ca. 10,000 nucleotides in length (10 kilobases), which are believed to be the Moloney leukemia virus subunits. Both RNAs had an excess of a smaller, sarcoma-specific subunit, 5 kilobases (clone 3) or 6 kilobases (clone 124-5R) in length. Electron microscopy of intact 50 to 70S dimer RNA molecules showed for both clones many dimers of two small subunits, some dimers of two large subunits, but few if any heterodimers with one large and one small subunit. This result was unexpected because the sequences near the 5'end of the RNA subunits, which are believed to be involved in the dimer linkage, are probably homologous between the large and small subunits. We also observed that some small-small dimers migrated anomalously slowly on nondenaturing gels. The nature of this slow-migrating complex is unkown; it could be a higher aggregate of the small-small dimer with additional small or large subunits, or it could be an extended conformation of the small-small dimer.", "contents": "Structure of 50 to 70S RNA from Moloney sarcoma viruses. The 50 to 70S RNAs of two clonal isolates of defective Moloney sarcoma-leukemia helper virus complex were analyzed by gel electrophoresis and electron microscopy. The RNAs extracted from both clone 3 and clone 124-5R of Moloney sarcoma-leukemia virus complex contained some large monomer subunits ca. 10,000 nucleotides in length (10 kilobases), which are believed to be the Moloney leukemia virus subunits. Both RNAs had an excess of a smaller, sarcoma-specific subunit, 5 kilobases (clone 3) or 6 kilobases (clone 124-5R) in length. Electron microscopy of intact 50 to 70S dimer RNA molecules showed for both clones many dimers of two small subunits, some dimers of two large subunits, but few if any heterodimers with one large and one small subunit. This result was unexpected because the sequences near the 5'end of the RNA subunits, which are believed to be involved in the dimer linkage, are probably homologous between the large and small subunits. We also observed that some small-small dimers migrated anomalously slowly on nondenaturing gels. The nature of this slow-migrating complex is unkown; it could be a higher aggregate of the small-small dimer with additional small or large subunits, or it could be an extended conformation of the small-small dimer."}
{"id": "PMID:202750", "title": "Anatomy of bovine mammillitis DNA. I Restriction endonuclease maps of four populations of molecules that differ in the relative orientation of their long and short components.", "content": "In this paper, we report that the DNA of bovine mammillitis virus (BMV) consists of two covalently linked components that are 71.5 x 10(6) and 15.7 x 10(6) in molecular weight and designated L and S, respectively. We further report that the BMV DNA consists of four equimolar populations differing only in the orientation of the L and S components relative to each other. This conclusion is based on the following: (i) The sum molecular weight of fragments generated by digestion of BMV DNA with Hsu I, Hpa I, Bgl II, or Xba I significantly exceeds the established molecular weight of the intact DNA. (ii) In each digest, the fragments form three groups differing in molar concentration. In reference to the molar concentration of intact DNA, each enzyme digest contained a set of four fragments 0.25 M in concentration, a set of four fragments 0.5 M in concentration, and a variable size set, unique for each enzyme digest, 1.0 M in concentration. (iii) Experiments involving digestion of intact DNA by lambda exonuclease followed by restriction endonuclease digestion established that each of four 0.5 M fragments were positioned at the termini of the BMV DNA. (iv) Complete maps for the fragments generated by each enzyme established that the 0.25 M fragments arise by fusion of the sequences of the terminal fragments when these are juxtaposed as a consequence of the inversion of L and S components. The maps also established the dimensions of the L and S components. We conclude that the structure of BMV DNA is similar to that of HSV DNA previously shown to consist of two unequal size components that invert relative to each other.", "contents": "Anatomy of bovine mammillitis DNA. I Restriction endonuclease maps of four populations of molecules that differ in the relative orientation of their long and short components. In this paper, we report that the DNA of bovine mammillitis virus (BMV) consists of two covalently linked components that are 71.5 x 10(6) and 15.7 x 10(6) in molecular weight and designated L and S, respectively. We further report that the BMV DNA consists of four equimolar populations differing only in the orientation of the L and S components relative to each other. This conclusion is based on the following: (i) The sum molecular weight of fragments generated by digestion of BMV DNA with Hsu I, Hpa I, Bgl II, or Xba I significantly exceeds the established molecular weight of the intact DNA. (ii) In each digest, the fragments form three groups differing in molar concentration. In reference to the molar concentration of intact DNA, each enzyme digest contained a set of four fragments 0.25 M in concentration, a set of four fragments 0.5 M in concentration, and a variable size set, unique for each enzyme digest, 1.0 M in concentration. (iii) Experiments involving digestion of intact DNA by lambda exonuclease followed by restriction endonuclease digestion established that each of four 0.5 M fragments were positioned at the termini of the BMV DNA. (iv) Complete maps for the fragments generated by each enzyme established that the 0.25 M fragments arise by fusion of the sequences of the terminal fragments when these are juxtaposed as a consequence of the inversion of L and S components. The maps also established the dimensions of the L and S components. We conclude that the structure of BMV DNA is similar to that of HSV DNA previously shown to consist of two unequal size components that invert relative to each other."}
{"id": "PMID:202751", "title": "Encephalomyocarditis virus RNA. III. Presence of a genome-associated protein.", "content": "A low-molecular-weight protein was found to be associated with intact 35S RNA isolated from purified encephalomyocarditis virus. This protein was positively charged at pH 3.5, sensitive to proteinase K treatment, and labeled with either 3H-amino acids or 32Pi.", "contents": "Encephalomyocarditis virus RNA. III. Presence of a genome-associated protein. A low-molecular-weight protein was found to be associated with intact 35S RNA isolated from purified encephalomyocarditis virus. This protein was positively charged at pH 3.5, sensitive to proteinase K treatment, and labeled with either 3H-amino acids or 32Pi."}
{"id": "PMID:202752", "title": "Inhibition of herpes simplex virus type 1 replication in temperature-sensitive cell cycle mutants.", "content": "Herpes simplex virus type 1 DNA synthesis and infections progeny production were studied in five different conditional hamster (BHK-21) cell cycle mutants. At the nonpermissive temperature (39.5 degrees C), both events were strongly inhibited in four of these cell lines. The degree of inhibition was a reproducible characteristic of each cell mutant and in two cases was dependent upon the multiplicity of infection. Experiments involving shifts to the nonpermissive temperature at least 3 h postinfection at 33.5 degrees C suggested that the defects in viral replication were not due to faulty adsorption, penetration, or uncoating, whereas experiments involving shifts of infected cells from the nonpermissive temperature to 33.5 degrees C revealed the reversible nature of the inhibition.", "contents": "Inhibition of herpes simplex virus type 1 replication in temperature-sensitive cell cycle mutants. Herpes simplex virus type 1 DNA synthesis and infections progeny production were studied in five different conditional hamster (BHK-21) cell cycle mutants. At the nonpermissive temperature (39.5 degrees C), both events were strongly inhibited in four of these cell lines. The degree of inhibition was a reproducible characteristic of each cell mutant and in two cases was dependent upon the multiplicity of infection. Experiments involving shifts to the nonpermissive temperature at least 3 h postinfection at 33.5 degrees C suggested that the defects in viral replication were not due to faulty adsorption, penetration, or uncoating, whereas experiments involving shifts of infected cells from the nonpermissive temperature to 33.5 degrees C revealed the reversible nature of the inhibition."}
{"id": "PMID:202753", "title": "Alterations in the protein synthetic apparatus of Friend erythroleukemia cells infected with vesicular stomatitis virus or herpes simplex virus.", "content": "We have compared the effects of infection with herpes simplex virus (HSV) and vesicular stomatitis virus (VSV) on the protein synthetic apparatus of Friend erythroleukemia cells. Previous studies demonstrated that infection with HSV rapidly shuts off the synthesis of globin and other cellular polypeptides (Y. Nischioka and S. Silverstein, 1977, Proc. Natl. Acad. Sci. U.S.A. 74: 2370-2374). In contrast to these findings, globin synthesis persists in Friend erythroleukemia cells infected with VSV. Physical measurements of the size of bulk-infected cell mRNA, using hybridization with polyuridylic acid, demonstrated that there was no detectable change in the size of mRNA's after infection with VSV. A comparison of the kinetics of hybridization of cytoplasmic RNA extracted from cells infected with either HSV or VSV with globin complementary DNA revealed that by 4 h postinfection with HSV only about 15% of the globin mRNA sequences remained, whereas there was no discernible change in the sequence abundance of globin mRNA in VSV-infected cells.", "contents": "Alterations in the protein synthetic apparatus of Friend erythroleukemia cells infected with vesicular stomatitis virus or herpes simplex virus. We have compared the effects of infection with herpes simplex virus (HSV) and vesicular stomatitis virus (VSV) on the protein synthetic apparatus of Friend erythroleukemia cells. Previous studies demonstrated that infection with HSV rapidly shuts off the synthesis of globin and other cellular polypeptides (Y. Nischioka and S. Silverstein, 1977, Proc. Natl. Acad. Sci. U.S.A. 74: 2370-2374). In contrast to these findings, globin synthesis persists in Friend erythroleukemia cells infected with VSV. Physical measurements of the size of bulk-infected cell mRNA, using hybridization with polyuridylic acid, demonstrated that there was no detectable change in the size of mRNA's after infection with VSV. A comparison of the kinetics of hybridization of cytoplasmic RNA extracted from cells infected with either HSV or VSV with globin complementary DNA revealed that by 4 h postinfection with HSV only about 15% of the globin mRNA sequences remained, whereas there was no discernible change in the sequence abundance of globin mRNA in VSV-infected cells."}
{"id": "PMID:202754", "title": "5' Terminus of defective and nondefective Sendai viral genomes is ppp Ap.", "content": "Using RNase T2 digestion of 32P-labeled Sendai virus nondefective and defective-interfering RNAs, the 5' termini were isolated and demonstrated to be pppAp for both the plus and minus strands.", "contents": "5' Terminus of defective and nondefective Sendai viral genomes is ppp Ap. Using RNase T2 digestion of 32P-labeled Sendai virus nondefective and defective-interfering RNAs, the 5' termini were isolated and demonstrated to be pppAp for both the plus and minus strands."}
{"id": "PMID:202755", "title": "Initiation points for DNA replication in nontransformed and simian virus 40-transformed BALB/c 3T3 cells.", "content": "The number of initiation points for DNA synthesis per unit length of DNA in rapidly growing cells is greater for simian virus 40-transformed than for nontransformed BALB/c 3T3 cells.", "contents": "Initiation points for DNA replication in nontransformed and simian virus 40-transformed BALB/c 3T3 cells. The number of initiation points for DNA synthesis per unit length of DNA in rapidly growing cells is greater for simian virus 40-transformed than for nontransformed BALB/c 3T3 cells."}
{"id": "PMID:202756", "title": "Adenovirus DNA synthesis in vitro in an isolated complex.", "content": "DNA-protein complexes isolated from adenovirus-infected cells by a modification of the M-band technique were used as an in vitro system for the study of adenovirus DNA replication. The synthesis in vitro was semiconservative, inhibited by N-ethylmaleimide, and stimulated by ATP. Studies on DNA-negative mutants of adenovirus showed that the DNA synthesis in vitro represents a continuation of adenovirus DNA replication in vivo. DNA synthesis in vitro was inhibited 38% by 20 microgram of phosphonoacetic acid per ml, which is several-fold higher than the inhibition obtained with purified DNA polymerase beta or gamma, but was similar to the degree of inhibition of DNA polymerase alpha. DNA synthesis in complexes from uninfected cells was much less sensitive to inhibition by phosphonoacetic acid. In addition, complexes from infected cells contained a greater proportion of the alpha-polymerase than complexes from uninfected cells, suggesting that an association of alpha-polymerase with the replication complex may be occurring during adenovirus infection, with subsequent utilization of the alpha-polymerase for viral DNA synthesis.", "contents": "Adenovirus DNA synthesis in vitro in an isolated complex. DNA-protein complexes isolated from adenovirus-infected cells by a modification of the M-band technique were used as an in vitro system for the study of adenovirus DNA replication. The synthesis in vitro was semiconservative, inhibited by N-ethylmaleimide, and stimulated by ATP. Studies on DNA-negative mutants of adenovirus showed that the DNA synthesis in vitro represents a continuation of adenovirus DNA replication in vivo. DNA synthesis in vitro was inhibited 38% by 20 microgram of phosphonoacetic acid per ml, which is several-fold higher than the inhibition obtained with purified DNA polymerase beta or gamma, but was similar to the degree of inhibition of DNA polymerase alpha. DNA synthesis in complexes from uninfected cells was much less sensitive to inhibition by phosphonoacetic acid. In addition, complexes from infected cells contained a greater proportion of the alpha-polymerase than complexes from uninfected cells, suggesting that an association of alpha-polymerase with the replication complex may be occurring during adenovirus infection, with subsequent utilization of the alpha-polymerase for viral DNA synthesis."}
{"id": "PMID:202757", "title": "Radiobiological inactivation of Epstein-Barr virus.", "content": "Lymphocyte transforming properties of B95-8 strain Epstein-Barr virus (EBV) are very sensitive to inactivation by either UV or X irradiation. No dose of irradiation increases the transforming capacity of EBV. The X-ray dose needed for inactivation of EBV transformation (dose that results in 37% survival, 60,000 rads) is similar to the dose required for inactivation of plaque formation by herpes simplex virus type 1 (Fischer strain). Although herpes simplex virus is more sensitive than EBV to UV irradiation, this difference is most likely due to differences in the kinetics or mechanisms of repair of UV damage to the two viruses. The results lead to the hypothesis that a large part, or perhaps all, of the EBV genome is in some way needed to initiate transformation. The abilities of EBV to stimulate host cell DNA synthesis, to induce nuclear antigen, and to immortalize are inactivated in parallel. All clones of marmoset cells transformed by irradiated virus produce extracellular transforming virus. These findings suggest that the abilities of the virus to transform and to replicate complete progeny are inactivated together. The amounts of UV and X irradiation that inactivate transformation by B95-8 virus are less than the dose needed to inactivate early antigen induction by the nontransforming P(3)HR-1 strain of EBV. Based on radiobiological inactivation, 10 to 50% of the genome is needed for early antigen induction. Inactivation of early antigen induction is influenced by the cells in which the assay is performed. Inactivation proceeds more rapidly in EBV genome-free cells than in genome carrier Raji or in P(3)HR-1 converted EBV genome-free cells clone B(1). These results indicate that the resident EBV genome participates in the early antigen induction process. Variation in radio-biological killing of B95-8 and P(3)HR-1 EBV is not attributable to variations in the repair capacities of the cells in which the viruses were assayed, since inactivation of HSV was the same in primary lymphocytes and in all lymphoid cell lines tested.", "contents": "Radiobiological inactivation of Epstein-Barr virus. Lymphocyte transforming properties of B95-8 strain Epstein-Barr virus (EBV) are very sensitive to inactivation by either UV or X irradiation. No dose of irradiation increases the transforming capacity of EBV. The X-ray dose needed for inactivation of EBV transformation (dose that results in 37% survival, 60,000 rads) is similar to the dose required for inactivation of plaque formation by herpes simplex virus type 1 (Fischer strain). Although herpes simplex virus is more sensitive than EBV to UV irradiation, this difference is most likely due to differences in the kinetics or mechanisms of repair of UV damage to the two viruses. The results lead to the hypothesis that a large part, or perhaps all, of the EBV genome is in some way needed to initiate transformation. The abilities of EBV to stimulate host cell DNA synthesis, to induce nuclear antigen, and to immortalize are inactivated in parallel. All clones of marmoset cells transformed by irradiated virus produce extracellular transforming virus. These findings suggest that the abilities of the virus to transform and to replicate complete progeny are inactivated together. The amounts of UV and X irradiation that inactivate transformation by B95-8 virus are less than the dose needed to inactivate early antigen induction by the nontransforming P(3)HR-1 strain of EBV. Based on radiobiological inactivation, 10 to 50% of the genome is needed for early antigen induction. Inactivation of early antigen induction is influenced by the cells in which the assay is performed. Inactivation proceeds more rapidly in EBV genome-free cells than in genome carrier Raji or in P(3)HR-1 converted EBV genome-free cells clone B(1). These results indicate that the resident EBV genome participates in the early antigen induction process. Variation in radio-biological killing of B95-8 and P(3)HR-1 EBV is not attributable to variations in the repair capacities of the cells in which the viruses were assayed, since inactivation of HSV was the same in primary lymphocytes and in all lymphoid cell lines tested."}
{"id": "PMID:202758", "title": "Glycoproteins of avian tumor virus recombinants: evidence for intragenic crossing-over.", "content": "The envelope glycoproteins of several avian tumor virus recombinants selected for the host range of a leukosis virus and the transforming function of a sarcoma virus were compared with each other and with those of their parents. It was found that the glycoproteins of different recombinant viruses, derived from the same parents, differed in their electrophoretic mobilities measured in polyacrylmide gels. The glycoproteins that had lower electrophoretic mobilities had higher precentages of carbohydrate. The carbohydrate of viral glycoproteins was estimated to range between 8 and 18% from their buoyant densities in CsCl, using known glycoproteins as standards. After exhaustive Pronase digestion, the carbohydrate was recovered from viral glycoproteins as a mixture of glycopeptides with molecular weights ranging from 2,500 to 5,000. It was estimated that distinct viral glycoproteins contained between two and five such oligosaccharide chains and that the glycoproteins of different recombinants expressing the same host range marker may differ in the number of oligosaccharide chains and consequently also in their polypeptide structure. Those with lower electrophoretic mobility contain more oligosaccharide chains per molecule than those with higher electrophoretic mobilities. It is suggested that not oligosaccharide chains define the viral host range.", "contents": "Glycoproteins of avian tumor virus recombinants: evidence for intragenic crossing-over. The envelope glycoproteins of several avian tumor virus recombinants selected for the host range of a leukosis virus and the transforming function of a sarcoma virus were compared with each other and with those of their parents. It was found that the glycoproteins of different recombinant viruses, derived from the same parents, differed in their electrophoretic mobilities measured in polyacrylmide gels. The glycoproteins that had lower electrophoretic mobilities had higher precentages of carbohydrate. The carbohydrate of viral glycoproteins was estimated to range between 8 and 18% from their buoyant densities in CsCl, using known glycoproteins as standards. After exhaustive Pronase digestion, the carbohydrate was recovered from viral glycoproteins as a mixture of glycopeptides with molecular weights ranging from 2,500 to 5,000. It was estimated that distinct viral glycoproteins contained between two and five such oligosaccharide chains and that the glycoproteins of different recombinants expressing the same host range marker may differ in the number of oligosaccharide chains and consequently also in their polypeptide structure. Those with lower electrophoretic mobility contain more oligosaccharide chains per molecule than those with higher electrophoretic mobilities. It is suggested that not oligosaccharide chains define the viral host range."}
{"id": "PMID:202759", "title": "Adenocarcinoma of the urachus.", "content": "During the last 50 years 8 patients with adenocarcinoma of the urachus were managed at our hospital. The various modalities of therapy included radiation therapy, transurethral resection, segmental resection of the bladder and total cystectomy. A retrospective analysis of these cases is presented, including the histologic patterns, sites of spread and survival according to therapy.", "contents": "Adenocarcinoma of the urachus. During the last 50 years 8 patients with adenocarcinoma of the urachus were managed at our hospital. The various modalities of therapy included radiation therapy, transurethral resection, segmental resection of the bladder and total cystectomy. A retrospective analysis of these cases is presented, including the histologic patterns, sites of spread and survival according to therapy."}
{"id": "PMID:202775", "title": "[2 models of indomethacin-induced arterial hypertension in rats in chronic experiments].", "content": "Chronic administration of small doses of prostaglandin-synthesis inhibitor indometacin against the background of a salt load or unilateral nephrectomy induces the development of arterial hypertension in rats. Arterial pressure increases (two fold on the average) on the 6th week of the experiment in 60-80% of the animals. Arterial hypertension developing against the background of a salt load is marked by retention of sodium in the organism and increase the intravascular volume, while that developing in unilateral nephrectomy--by increased sodium excretion and reduced intravascular volume. Depressed activity of the renin-angiotensin-aldosterone system and conspicious changes in the renal vascular channel are noted in both forms of arterial hypertension. It is assumed that disorders in the metabolism of cyclic nucleotides underlie the changes occurring in the renal vessels due to the effect of indometacin. Similar generalized changes in the peripheral vascular channel on the whole may be the cause of the increased vascular resistance and one of the causative factors of the hypertension development.", "contents": "[2 models of indomethacin-induced arterial hypertension in rats in chronic experiments]. Chronic administration of small doses of prostaglandin-synthesis inhibitor indometacin against the background of a salt load or unilateral nephrectomy induces the development of arterial hypertension in rats. Arterial pressure increases (two fold on the average) on the 6th week of the experiment in 60-80% of the animals. Arterial hypertension developing against the background of a salt load is marked by retention of sodium in the organism and increase the intravascular volume, while that developing in unilateral nephrectomy--by increased sodium excretion and reduced intravascular volume. Depressed activity of the renin-angiotensin-aldosterone system and conspicious changes in the renal vascular channel are noted in both forms of arterial hypertension. It is assumed that disorders in the metabolism of cyclic nucleotides underlie the changes occurring in the renal vessels due to the effect of indometacin. Similar generalized changes in the peripheral vascular channel on the whole may be the cause of the increased vascular resistance and one of the causative factors of the hypertension development."}
{"id": "PMID:202776", "title": "[Typology of the hyperlipoproteinemias in ischemic heart disease].", "content": "A total of 227 patients with ischaemic heart disease were examined. Hypercholesterolemia was revealed in 72 percent, hypertriglyceridemia--in 48 percent, and various types of hyperlipoproteinemia--in 82 percent. Type II hyperlipoproteinemia was seen most often (59 percent), type IV in 21 percent. Hyperlipoproteinemia of Type IV was found in men twice as often as in women (29 and 13 percent respectively). Women had normal levels of blood serum lipoproteins 1.5 times more often. No spontaneous normalization of hyperlopoproteinemia was noted.", "contents": "[Typology of the hyperlipoproteinemias in ischemic heart disease]. A total of 227 patients with ischaemic heart disease were examined. Hypercholesterolemia was revealed in 72 percent, hypertriglyceridemia--in 48 percent, and various types of hyperlipoproteinemia--in 82 percent. Type II hyperlipoproteinemia was seen most often (59 percent), type IV in 21 percent. Hyperlipoproteinemia of Type IV was found in men twice as often as in women (29 and 13 percent respectively). Women had normal levels of blood serum lipoproteins 1.5 times more often. No spontaneous normalization of hyperlopoproteinemia was noted."}
{"id": "PMID:202777", "title": "[Crystalline corneal dystrophy (Schnyder) in the presence of familial type IIa hyperlipoproteinaemia (author's transl)].", "content": "A family with dominant autosomal hyperlipoproteinaemia typ IIa is reported. One sibling, a 19-year-old man, showed in addition to the hyperlipoproteinaemia typical corneal signs of crystalline corneal dystrophy of Schnyder. From 1964 to 1976 these corneal deposits increased. The problems of hyperlipoproteinaemia combined with corneal crystalline dystrophy are discussed.", "contents": "[Crystalline corneal dystrophy (Schnyder) in the presence of familial type IIa hyperlipoproteinaemia (author's transl)]. A family with dominant autosomal hyperlipoproteinaemia typ IIa is reported. One sibling, a 19-year-old man, showed in addition to the hyperlipoproteinaemia typical corneal signs of crystalline corneal dystrophy of Schnyder. From 1964 to 1976 these corneal deposits increased. The problems of hyperlipoproteinaemia combined with corneal crystalline dystrophy are discussed."}
{"id": "PMID:202798", "title": "A naturally occurring epizootic caused by Sendai virus in breeding and aging rodent colonies. I. Infection in the mouse.", "content": "An acute Sendai virus epizootic occurred simultaneously in a breeding colony, in experimental and stock animal rooms, and in a colony of aging mice. During the 2-month period that the infection was at its maximum, death rates were approximately doubled. In some strains, the preweanling death rate reached 100%. RFM and BALB/c mice were most susceptible and NZB mice least susceptible. The mortality during the period of Sendai virus infection was increased for most strains and age groups except for the oldest female RFM and NZB mice. Death rates during the epizootic were lowest in young adult mice (greater than 10 weeks of age) and highest in the very young mice (less than 10 weeks of age) and in the oldest male and the moderately aged female mice. Although a substantial number of older mice died during the epizootic, examination of the age-specific death rates indicated that the increase in deaths remained relatively constant for all ages over 10 weeks. This showed that the older mice were not more susceptible to Sendai virus infection. As a sequela of the epizootic, focal chronic pneumonia was found in 10-40% of the mice coming to necropsy even 1 year later.", "contents": "A naturally occurring epizootic caused by Sendai virus in breeding and aging rodent colonies. I. Infection in the mouse. An acute Sendai virus epizootic occurred simultaneously in a breeding colony, in experimental and stock animal rooms, and in a colony of aging mice. During the 2-month period that the infection was at its maximum, death rates were approximately doubled. In some strains, the preweanling death rate reached 100%. RFM and BALB/c mice were most susceptible and NZB mice least susceptible. The mortality during the period of Sendai virus infection was increased for most strains and age groups except for the oldest female RFM and NZB mice. Death rates during the epizootic were lowest in young adult mice (greater than 10 weeks of age) and highest in the very young mice (less than 10 weeks of age) and in the oldest male and the moderately aged female mice. Although a substantial number of older mice died during the epizootic, examination of the age-specific death rates indicated that the increase in deaths remained relatively constant for all ages over 10 weeks. This showed that the older mice were not more susceptible to Sendai virus infection. As a sequela of the epizootic, focal chronic pneumonia was found in 10-40% of the mice coming to necropsy even 1 year later."}
{"id": "PMID:202799", "title": "A naturally occurring epizootic caused by Sendai virus in breeding and aging rodent colonies. II. Infection in the rat.", "content": "Sendai virus infected a hysterectomy derived, barrier maintained breeding colony and a conventional aging rat colony. The virus produced seroconversion in the colonies followed by a 7-month period of decreasing titers. Clinical signs were absent during the months when titers were highest, and there was no increase in mortality, but multifocal interstitial pneumonia with perivascular and peribronchial cuffing by lymphocytes and plasma cells was present in rat lungs examined histologically. Such lesions were absent before the period of seroconversion. During the months of declining titers, the interstitial and perivascular lesions decreased in frequency and severity. The peribronchial lesions did not decrease, however, and were still present in many rats 7 months after the acute infection. Attempts to isolate the virus from weanling rats were unsuccessful.", "contents": "A naturally occurring epizootic caused by Sendai virus in breeding and aging rodent colonies. II. Infection in the rat. Sendai virus infected a hysterectomy derived, barrier maintained breeding colony and a conventional aging rat colony. The virus produced seroconversion in the colonies followed by a 7-month period of decreasing titers. Clinical signs were absent during the months when titers were highest, and there was no increase in mortality, but multifocal interstitial pneumonia with perivascular and peribronchial cuffing by lymphocytes and plasma cells was present in rat lungs examined histologically. Such lesions were absent before the period of seroconversion. During the months of declining titers, the interstitial and perivascular lesions decreased in frequency and severity. The peribronchial lesions did not decrease, however, and were still present in many rats 7 months after the acute infection. Attempts to isolate the virus from weanling rats were unsuccessful."}
{"id": "PMID:202800", "title": "Development of a guinea pig colony free of complement-fixing antibodies to parainfluenza virus.", "content": "Complement-fixing antibodies to parainfluenza 3 virus were found in Hartley strain [Cds: (HA)] guinea pigs from the authors' production colony. The prevalence and distribution of these antibodies were determined by testing guinea pigs of five age categories: 4 weeks, 8 weeks, 12 weeks, 6 months to 1 year, and over 1 year of age. Forty-seven percent (28 of 60) were positive to parainfluenza 3 antigen. Positive reactors were found in all age groups except those 8 weeks old. The 12-week-old group had the highest titers; the group over 1 year of age had the highest percentage of positives (92%). When 8-week-old guinea pigs were isolated, 55% were positive at some time between 8 and 34 weeks of age. The titers characteristically rose rapidly and then dropped slowly to low or undetectable levels. Four pairs of breeders over 6 months of age (most of whom were positive for parainfluenza 3 virus antibodies and, therefore, presumed to be immune to the virus) were isolated and allowed to breed. Their offspring  were found to be free of complement-fixing antibodies to parainfluenza 3 virus.", "contents": "Development of a guinea pig colony free of complement-fixing antibodies to parainfluenza virus. Complement-fixing antibodies to parainfluenza 3 virus were found in Hartley strain [Cds: (HA)] guinea pigs from the authors' production colony. The prevalence and distribution of these antibodies were determined by testing guinea pigs of five age categories: 4 weeks, 8 weeks, 12 weeks, 6 months to 1 year, and over 1 year of age. Forty-seven percent (28 of 60) were positive to parainfluenza 3 antigen. Positive reactors were found in all age groups except those 8 weeks old. The 12-week-old group had the highest titers; the group over 1 year of age had the highest percentage of positives (92%). When 8-week-old guinea pigs were isolated, 55% were positive at some time between 8 and 34 weeks of age. The titers characteristically rose rapidly and then dropped slowly to low or undetectable levels. Four pairs of breeders over 6 months of age (most of whom were positive for parainfluenza 3 virus antibodies and, therefore, presumed to be immune to the virus) were isolated and allowed to breed. Their offspring  were found to be free of complement-fixing antibodies to parainfluenza 3 virus."}
{"id": "PMID:202802", "title": "Cytochemical distinction between azurophils and catalase-containing granules in leukocytes. I. Studies in developing neutrophils and monocytes from patients with myeloperoxidase deficiency: comparison with peroxidase-deficient chicken heterophils.", "content": "The neutrophils and monocytes of two patients with hereditary myeloperoxidase (MPO) deficiency lacked MPO activity as determined by light and electron microscopic cytochemical staining. With a technique employing neutral 3,3'-diaminobenzidine, azurophils of precursor and mature neutrophils were devoid of MPO whereas eosinophil, basophil, and platelet peroxidases exhibited normal activity. After incubation in alkaline DAB medium, which stains catalase, some small granules were strongly reactive in both immature and mature neutrophils and monocytes. These catalase-containing granules were distinct from all other categories of granules. Their number decreased with maturation. In the presence of cyanide or aminotriazole, peroxidatic activity could also be detected in ellipsoid azurophils, although large spherical granules remained unreactive. This peroxidatic activity is apparently not due to MPO inasmuch as it has been demonstrated that this protein is not synthesized in these patients. Thus, the significance of the last finding is unclear but suggests a heterogeneity of azurophil content. In contrast to human MPO-deficient cells, chicken heterophils naturally devoid of peroxidase are unable to produce hydrogen peroxide upon phagocytosis and were also devoid of catalase-containing particles. This observation suggests that catalase is involved in the control of the intracellular level of hydrogen peroxide in human cells.", "contents": "Cytochemical distinction between azurophils and catalase-containing granules in leukocytes. I. Studies in developing neutrophils and monocytes from patients with myeloperoxidase deficiency: comparison with peroxidase-deficient chicken heterophils. The neutrophils and monocytes of two patients with hereditary myeloperoxidase (MPO) deficiency lacked MPO activity as determined by light and electron microscopic cytochemical staining. With a technique employing neutral 3,3'-diaminobenzidine, azurophils of precursor and mature neutrophils were devoid of MPO whereas eosinophil, basophil, and platelet peroxidases exhibited normal activity. After incubation in alkaline DAB medium, which stains catalase, some small granules were strongly reactive in both immature and mature neutrophils and monocytes. These catalase-containing granules were distinct from all other categories of granules. Their number decreased with maturation. In the presence of cyanide or aminotriazole, peroxidatic activity could also be detected in ellipsoid azurophils, although large spherical granules remained unreactive. This peroxidatic activity is apparently not due to MPO inasmuch as it has been demonstrated that this protein is not synthesized in these patients. Thus, the significance of the last finding is unclear but suggests a heterogeneity of azurophil content. In contrast to human MPO-deficient cells, chicken heterophils naturally devoid of peroxidase are unable to produce hydrogen peroxide upon phagocytosis and were also devoid of catalase-containing particles. This observation suggests that catalase is involved in the control of the intracellular level of hydrogen peroxide in human cells."}
{"id": "PMID:202808", "title": "Glycosylation of VSV glycoprotein is similar in cystic fibrosis, heterozygous carrier, and normal human fibroblasts.", "content": "The single envelope glycoprotein of vesicular stomatitis virus was used as a specific probe of glycosyltransferase activities in fibroblasts from two cystic fibrosis patients, an obligate heterozygous carrier and a normal individual. Gel filtration of pronase-digested glycopeptides from both purified virions and infected cell-associated VSV glycoprotein which had been labeled with[3H] glucosamine did not reveal any significant differences in the glycosylation patterns between the different cell cultures. All 4 cell lines were apparently able to synthesize the mannose- and glucosamine- containing core structure and branch chains terminating in sialic acid which are characteristic of asparagine-linked carbohydrate side chains in cellular glycoproteins. Analysis of tryptic glycopeptides by anion-exchange chromotography indicated that the same 2 major sites on the virus polypeptide were recognized and glycosylated in all 4 VSV-infected cell cultures. These studies suggest that the basic biochemical defect(s) in cystic fibrosis is not an absence or deficiency in enzymes responsible for the biosynthesis of complex carbohydrate side chains.", "contents": "Glycosylation of VSV glycoprotein is similar in cystic fibrosis, heterozygous carrier, and normal human fibroblasts. The single envelope glycoprotein of vesicular stomatitis virus was used as a specific probe of glycosyltransferase activities in fibroblasts from two cystic fibrosis patients, an obligate heterozygous carrier and a normal individual. Gel filtration of pronase-digested glycopeptides from both purified virions and infected cell-associated VSV glycoprotein which had been labeled with[3H] glucosamine did not reveal any significant differences in the glycosylation patterns between the different cell cultures. All 4 cell lines were apparently able to synthesize the mannose- and glucosamine- containing core structure and branch chains terminating in sialic acid which are characteristic of asparagine-linked carbohydrate side chains in cellular glycoproteins. Analysis of tryptic glycopeptides by anion-exchange chromotography indicated that the same 2 major sites on the virus polypeptide were recognized and glycosylated in all 4 VSV-infected cell cultures. These studies suggest that the basic biochemical defect(s) in cystic fibrosis is not an absence or deficiency in enzymes responsible for the biosynthesis of complex carbohydrate side chains."}
{"id": "PMID:202809", "title": "Coenzyme models. 10. Rapid oxidation of NADH by a flavin immobilized in cationic polyelectrolytes.", "content": "The title flavin rapidly oxidizes NADH, the observed enhancement being of 460--4650-fold compared with 3-methyltetra-O-acetylriboflavin. Analysis of the kinetic data at 30 degrees C established that the reaction proceeds according to the Michaelis-Menten kinetics at low ionic strength (mu = 0.02: Km = ca. 10(-5) M, kact. = 0.06-0.37 s-1) and according to the simple second-order kinetics at high ionic strength (mu = 0.3), the largest rate difference being 342-fold. On the other hand, the oxidation of 1-benzyl-1,4-dihydronicotinamide, a NADH model compound, was not accelerated by the use of the title flavin. It is concluded, therefore, that the formation of the polymeric flavin-NADH complexes due to the electrostatic interaction is responsible for the marked rate enhancement. This is the first example that the oxidation of NADH is facilitated in the nonenzymatic system.", "contents": "Coenzyme models. 10. Rapid oxidation of NADH by a flavin immobilized in cationic polyelectrolytes. The title flavin rapidly oxidizes NADH, the observed enhancement being of 460--4650-fold compared with 3-methyltetra-O-acetylriboflavin. Analysis of the kinetic data at 30 degrees C established that the reaction proceeds according to the Michaelis-Menten kinetics at low ionic strength (mu = 0.02: Km = ca. 10(-5) M, kact. = 0.06-0.37 s-1) and according to the simple second-order kinetics at high ionic strength (mu = 0.3), the largest rate difference being 342-fold. On the other hand, the oxidation of 1-benzyl-1,4-dihydronicotinamide, a NADH model compound, was not accelerated by the use of the title flavin. It is concluded, therefore, that the formation of the polymeric flavin-NADH complexes due to the electrostatic interaction is responsible for the marked rate enhancement. This is the first example that the oxidation of NADH is facilitated in the nonenzymatic system."}
{"id": "PMID:202816", "title": "Plasma membrane associated metabolic parameters and the aging of human diploid fibroblasts.", "content": "Substrate uptake, portions of the cyclic AMP system, membrane fluidity and cellular phospholipid content are some of the parameters which are structurally associated with the plasma membrane and which have been linked to the control of cell proliferation. These parameters were studied with respect to cellular aging of human embryo lung fibroblasts (HELF) in culture. We observed in late passage an increase in the rate of uridine transport and in cellular cyclic AMP levels. These results were examined in relation to the increase in cell volume which occurs in senescing HELF. We also observed an increase in Vmax of uridine transport, and a decrease in the Km of cyclic AMP phosphodiesterase (PDE) as quiescent, passage 18-25, HELF were stimulated to divide with fresh serum. A similar effect of serum occurred in late passage (p. 43) cells despite the inability of these late passage cultures to undergo further proliferation. There was no change in cAMP-PDE activity with increasing passage number suggesting that the observed alterations of the cAMP levels, basal and in response to extracellular effectors, were due to alterations in the adenyl cyclase system. We observed no change in senescent HELF in membrane fluidity or phospholipid and neutral fat content.", "contents": "Plasma membrane associated metabolic parameters and the aging of human diploid fibroblasts. Substrate uptake, portions of the cyclic AMP system, membrane fluidity and cellular phospholipid content are some of the parameters which are structurally associated with the plasma membrane and which have been linked to the control of cell proliferation. These parameters were studied with respect to cellular aging of human embryo lung fibroblasts (HELF) in culture. We observed in late passage an increase in the rate of uridine transport and in cellular cyclic AMP levels. These results were examined in relation to the increase in cell volume which occurs in senescing HELF. We also observed an increase in Vmax of uridine transport, and a decrease in the Km of cyclic AMP phosphodiesterase (PDE) as quiescent, passage 18-25, HELF were stimulated to divide with fresh serum. A similar effect of serum occurred in late passage (p. 43) cells despite the inability of these late passage cultures to undergo further proliferation. There was no change in cAMP-PDE activity with increasing passage number suggesting that the observed alterations of the cAMP levels, basal and in response to extracellular effectors, were due to alterations in the adenyl cyclase system. We observed no change in senescent HELF in membrane fluidity or phospholipid and neutral fat content."}
{"id": "PMID:202824", "title": "Retrolabyrinthine approach: technique and newer indications.", "content": "Excellent exposure of the cerebellopontine angle is obtained by an approach through the mastoid posterior to the labyrinth. Since the major portion of the dissection is extradural, this approach is associated with a very low morbidity. The retrolabyrinthine approach has been used for several years for selective partial section of the posterior root of the trigeminal nerve in cases of trigeminal neuralgia. Complete relief of pain has been accomplished in 25 of 28 cases, and the other 3 patients had partial relief of pain. The only complications in these patients were partial hearing impairment in 2, and 1 partial abducens nerve paralysis which subsequently recovered completely. Two patients required secondary closure of cerebrospinal fluid leaks. This approach has also been used for exploration and biopsy of cerebellopontine angle tumors and for treatment of other cranial nerve problems. We conclude that the retrolabyrinthine approach is the preferred route to the cerebellopontine angle in a variety of clinical conditions.", "contents": "Retrolabyrinthine approach: technique and newer indications. Excellent exposure of the cerebellopontine angle is obtained by an approach through the mastoid posterior to the labyrinth. Since the major portion of the dissection is extradural, this approach is associated with a very low morbidity. The retrolabyrinthine approach has been used for several years for selective partial section of the posterior root of the trigeminal nerve in cases of trigeminal neuralgia. Complete relief of pain has been accomplished in 25 of 28 cases, and the other 3 patients had partial relief of pain. The only complications in these patients were partial hearing impairment in 2, and 1 partial abducens nerve paralysis which subsequently recovered completely. Two patients required secondary closure of cerebrospinal fluid leaks. This approach has also been used for exploration and biopsy of cerebellopontine angle tumors and for treatment of other cranial nerve problems. We conclude that the retrolabyrinthine approach is the preferred route to the cerebellopontine angle in a variety of clinical conditions."}
{"id": "PMID:202825", "title": "Melanotic neuroectodermal tumor of infancy.", "content": "The lack of knowledge regarding the histogenesis of the melanotic neuroectodermal tumor of infancy may account for the numerous names given to this neoplasm. The most appropriate nomenclature is melanotic neuroectodermal tumor of infancy as this term is both clinically descriptive and reflects its most likely histogenesis. The histological diagnosis of this neoplasm and its known benign biological behavior should be appreciated so that radical surgery or radiotherapy is not undertaken. Our case report includes an electron microscopic analysis which is in keeping with other reported cases. We have not confirmed high urinary VMA levels prior to resection of the lesion.", "contents": "Melanotic neuroectodermal tumor of infancy. The lack of knowledge regarding the histogenesis of the melanotic neuroectodermal tumor of infancy may account for the numerous names given to this neoplasm. The most appropriate nomenclature is melanotic neuroectodermal tumor of infancy as this term is both clinically descriptive and reflects its most likely histogenesis. The histological diagnosis of this neoplasm and its known benign biological behavior should be appreciated so that radical surgery or radiotherapy is not undertaken. Our case report includes an electron microscopic analysis which is in keeping with other reported cases. We have not confirmed high urinary VMA levels prior to resection of the lesion."}
{"id": "PMID:202837", "title": "Therapeutic innovation: a model for mental health planning.", "content": "Enlightened and progressive care of the mentally ill is closer to reality with the creation of the psychiatric halfway house. The halfway house is not an institutional edifice but a residential facility located in the community and indistinguishable from the other neighboring dwellings. The feature which sets apart the halfway house programmatically is its provision of a housing unit with some services for ex-hospital patients. Human incarceration continues to be a major enforcement instrument for the control of deviant behavior. Mental illness, as one type of poorly understood behavior, is for the most part controlled by institutionalizing the mentally ill person in a large dehumanized total institution such as the state mental hospital. Although major reforms are underway in many total institutions to humanize treatment procedures, innovative alternatives to custodial care are gaining impetus in the community. One such fascinating and rapidly expanding treatment innovation is the psychiatric halfway house. This presentation represents the results and implications of a comparative study of twenty such programs in the United States.", "contents": "Therapeutic innovation: a model for mental health planning. Enlightened and progressive care of the mentally ill is closer to reality with the creation of the psychiatric halfway house. The halfway house is not an institutional edifice but a residential facility located in the community and indistinguishable from the other neighboring dwellings. The feature which sets apart the halfway house programmatically is its provision of a housing unit with some services for ex-hospital patients. Human incarceration continues to be a major enforcement instrument for the control of deviant behavior. Mental illness, as one type of poorly understood behavior, is for the most part controlled by institutionalizing the mentally ill person in a large dehumanized total institution such as the state mental hospital. Although major reforms are underway in many total institutions to humanize treatment procedures, innovative alternatives to custodial care are gaining impetus in the community. One such fascinating and rapidly expanding treatment innovation is the psychiatric halfway house. This presentation represents the results and implications of a comparative study of twenty such programs in the United States."}
{"id": "PMID:202838", "title": "Selective effects of thiazide on intestinal absorption of calcium and adsorptive and renal hypercalciurias.", "content": "The effect of long-term thiazide therapy on the intestinal Ca absorption was measured in 10 well-defined cases of absorptive hypercalciuria with intestinal hyperabsorption of Ca and 8 with renal hypercalciuria (\"renal leak\" of Ca), many of whom had hyperabsorption of Ca. In most cases of absorptive hypercalciuria, the intestinal hyperabsorption of Ca persisted during treatment, despite restoration of normal urinary Ca. In contrast, the intestinal Ca absorption decreased significantly during thiazide therapy in 7 of 8 patients with renal hypercalciuria commensurate with the \"correction\" of the renal leak of Ca and secondary hyperparathyroidism. The results support the hypothesis that the intestinal hyperabsorption of Ca in absorptive hypercalciuria may be primary, whereas that in renal hypercalciuria may be associated with the hyperparathyroid state.", "contents": "Selective effects of thiazide on intestinal absorption of calcium and adsorptive and renal hypercalciurias. The effect of long-term thiazide therapy on the intestinal Ca absorption was measured in 10 well-defined cases of absorptive hypercalciuria with intestinal hyperabsorption of Ca and 8 with renal hypercalciuria (\"renal leak\" of Ca), many of whom had hyperabsorption of Ca. In most cases of absorptive hypercalciuria, the intestinal hyperabsorption of Ca persisted during treatment, despite restoration of normal urinary Ca. In contrast, the intestinal Ca absorption decreased significantly during thiazide therapy in 7 of 8 patients with renal hypercalciuria commensurate with the \"correction\" of the renal leak of Ca and secondary hyperparathyroidism. The results support the hypothesis that the intestinal hyperabsorption of Ca in absorptive hypercalciuria may be primary, whereas that in renal hypercalciuria may be associated with the hyperparathyroid state."}
{"id": "PMID:202841", "title": "Early detection of breast cancer.", "content": "One thousand referred patients with breast symptoms, a history of breast disease, or a family history of breast carcinoma have been examined at a suburban breast clinic. This is a preliminary survey of the data and results so far obtained from the initial examination of these patients. The examination consisted of history-taking by means of a questionnaire, physical examination of the breasts, thermography and xeromammography. A report correlating the findings was forwarded to the referring doctor in each case and any necessary action was indicated in the report. Seventy-eight patients were thought to require biopsy of a suspicious lump or mammographic lesion (7.8% of the total number); 76 patients actually had biopsies, and 18 patients were found to have carcinoma of the breast (23.8% of the total number of patients who had biopsies). The overall incidence of carcinoma in the 1000 women attending the clinic was 1.8% at the initial visit. While general population screening for breast carcinoma may be hard to justify, from both the detection rate and an economic point of view, it would appear from our experience to date that screening of selected high-risk referred patients is justified and, in fact, desirable.", "contents": "Early detection of breast cancer. One thousand referred patients with breast symptoms, a history of breast disease, or a family history of breast carcinoma have been examined at a suburban breast clinic. This is a preliminary survey of the data and results so far obtained from the initial examination of these patients. The examination consisted of history-taking by means of a questionnaire, physical examination of the breasts, thermography and xeromammography. A report correlating the findings was forwarded to the referring doctor in each case and any necessary action was indicated in the report. Seventy-eight patients were thought to require biopsy of a suspicious lump or mammographic lesion (7.8% of the total number); 76 patients actually had biopsies, and 18 patients were found to have carcinoma of the breast (23.8% of the total number of patients who had biopsies). The overall incidence of carcinoma in the 1000 women attending the clinic was 1.8% at the initial visit. While general population screening for breast carcinoma may be hard to justify, from both the detection rate and an economic point of view, it would appear from our experience to date that screening of selected high-risk referred patients is justified and, in fact, desirable."}
{"id": "PMID:202840", "title": "[Effect of oxygen concentration and the physiological state of cells on the respiration chain of Candida mycoderma].", "content": "The effect of oxygen concentration and limitation of the cultural growth by the substrate to be oxidized on the functionation of the respiration chain and the ratio of cytochromes a : c : b was studied in intact cells of Candida mycoderma. As the concentration of oxygen in the medium decreases and the growth of the culture slows down, the cyanide-resistant pathway of electron transport (CrPET), which is inhibited by benzhydroxamic acid, is found in the yeast cells. At the same time, the content of cytochrome a in the cells decreases, probably because cytochrome oxidase is now less involved in electron transport via CrPET, whereas the content of cytochromes c and b increases. The latter fact seems to be due to the activation of the cytochrome-c-peroxidase pathway of electron transport whose functioning in the studied strain of C. mycoderma has been shown earlier. CrPET was found to function also at a high concentration of oxygen, but under conditions of the transition of the culture to the stationary phase, as well as during the incubation of resting cells taken at the exponential phase of growth. The manifestation of CrPET in conditions of a low concentration of oxygen can be caused not only by the direct effect of its deficiency on the respiration chain, but also by a change in the physiological state of yeast cells at their growth decelerates or ceases.", "contents": "[Effect of oxygen concentration and the physiological state of cells on the respiration chain of Candida mycoderma]. The effect of oxygen concentration and limitation of the cultural growth by the substrate to be oxidized on the functionation of the respiration chain and the ratio of cytochromes a : c : b was studied in intact cells of Candida mycoderma. As the concentration of oxygen in the medium decreases and the growth of the culture slows down, the cyanide-resistant pathway of electron transport (CrPET), which is inhibited by benzhydroxamic acid, is found in the yeast cells. At the same time, the content of cytochrome a in the cells decreases, probably because cytochrome oxidase is now less involved in electron transport via CrPET, whereas the content of cytochromes c and b increases. The latter fact seems to be due to the activation of the cytochrome-c-peroxidase pathway of electron transport whose functioning in the studied strain of C. mycoderma has been shown earlier. CrPET was found to function also at a high concentration of oxygen, but under conditions of the transition of the culture to the stationary phase, as well as during the incubation of resting cells taken at the exponential phase of growth. The manifestation of CrPET in conditions of a low concentration of oxygen can be caused not only by the direct effect of its deficiency on the respiration chain, but also by a change in the physiological state of yeast cells at their growth decelerates or ceases."}
{"id": "PMID:202858", "title": "Deletion mutants of temperate Bacillus subtilis bacteriophage phi105.", "content": "Six deletion mutants of temperate Bacillus subtilis phage phi105 have been isolated on the basis of their increased resistance to chelating agents. The size and position of the deletions was determined by electronmicroscopy of DNA heteroduplexes. All deletions are located in a region about 55-70% from one end of the DNA molecule, in the right half of the known genetic map of the phage. The segment 55-65% does not contain any genes essential for lytic growth or lysogenization. A gene(s) for immunity is located in a segment 65-70% from the left end. By electronmicroscopy by partially denatured phi105 DNA two A-T rich regions have been localized in the right half of the molecule. One of these regions falls within the non-essential 55-65% DNA segment.", "contents": "Deletion mutants of temperate Bacillus subtilis bacteriophage phi105. Six deletion mutants of temperate Bacillus subtilis phage phi105 have been isolated on the basis of their increased resistance to chelating agents. The size and position of the deletions was determined by electronmicroscopy of DNA heteroduplexes. All deletions are located in a region about 55-70% from one end of the DNA molecule, in the right half of the known genetic map of the phage. The segment 55-65% does not contain any genes essential for lytic growth or lysogenization. A gene(s) for immunity is located in a segment 65-70% from the left end. By electronmicroscopy by partially denatured phi105 DNA two A-T rich regions have been localized in the right half of the molecule. One of these regions falls within the non-essential 55-65% DNA segment."}
{"id": "PMID:202859", "title": "Restoration of mutability in non-mutable Escherichia coli carrying different plasmids.", "content": "N and I group plasmids, which increase methylmethane sulfonate (MMS) mutagenesis in lexA+ strains of E. coli WP2 may be divided into two classes: those restoring part of the mutability of lexA- stains (class I) and those leaving lexA- strains non-mutable (class II). Almost complete restoration of MMS mutability is obtained by class I plasmids in a partially suppressed lexA rnm strain, while clase II plasmids cause far fewer MMS revertants in this strain than in lexA+. A pair of class I and II plasmids in lexA- shows a synergistic effect on mutability. These two classes do not coincide with plasmid division into incompatibility groups.", "contents": "Restoration of mutability in non-mutable Escherichia coli carrying different plasmids. N and I group plasmids, which increase methylmethane sulfonate (MMS) mutagenesis in lexA+ strains of E. coli WP2 may be divided into two classes: those restoring part of the mutability of lexA- stains (class I) and those leaving lexA- strains non-mutable (class II). Almost complete restoration of MMS mutability is obtained by class I plasmids in a partially suppressed lexA rnm strain, while clase II plasmids cause far fewer MMS revertants in this strain than in lexA+. A pair of class I and II plasmids in lexA- shows a synergistic effect on mutability. These two classes do not coincide with plasmid division into incompatibility groups."}
{"id": "PMID:202860", "title": "An evaluation of D-glucosamine as a gratuitous catabolite repressor of Saccharomyces carlsbergensis.", "content": "Glucose represses mitochondrial biogenesis and the fermentation of maltose, galactose and sucrose in yeast. We have analyzed the effect of D-glucosamine on these functions in order to determine if it can produce a similar repression. It was found that glucosamine represses the respiration rate (QO2) but more rapidly than glucose and to a final level slightly higher than in glucose-treated cells. Derepression of the respiration rate following either glucose or glucosamine repression was similar. A two hour lag was followed by a linear increase in QO2 to the derepressed level. Both glucose and glucosamine repressed the level of cytochrome oxidase to the same level. Glucosamine was also found to repress maltose and galactose fermentation but not sucrose fermentation. The derepression of maltase synthesis was inhibited by glucosamine. The constitutive synthesis of maltase was repressed by the addition of glucosamine. Glucosamine was judged to produce a repressed state similar to glucose repression in many respects.", "contents": "An evaluation of D-glucosamine as a gratuitous catabolite repressor of Saccharomyces carlsbergensis. Glucose represses mitochondrial biogenesis and the fermentation of maltose, galactose and sucrose in yeast. We have analyzed the effect of D-glucosamine on these functions in order to determine if it can produce a similar repression. It was found that glucosamine represses the respiration rate (QO2) but more rapidly than glucose and to a final level slightly higher than in glucose-treated cells. Derepression of the respiration rate following either glucose or glucosamine repression was similar. A two hour lag was followed by a linear increase in QO2 to the derepressed level. Both glucose and glucosamine repressed the level of cytochrome oxidase to the same level. Glucosamine was also found to repress maltose and galactose fermentation but not sucrose fermentation. The derepression of maltase synthesis was inhibited by glucosamine. The constitutive synthesis of maltase was repressed by the addition of glucosamine. Glucosamine was judged to produce a repressed state similar to glucose repression in many respects."}
{"id": "PMID:202861", "title": "Effect of \"fasting\" and different concentrations of glucose on alpha-linolenic acid metabolism in HTC cells. Correlation with the ultrastructural study.", "content": "HTC cells are able to convert alpha-linolenic acid into higher homologs by desaturating and elongating reactions. When the cells were cultured in a Krebs Ringer bicarbonate solution (\"fasted cells\") a decrease in both biosynthetic reactions took place. \"Refeeding\" the cells with Swim's 77 medium without glucose enhanced the biosynthesis of polyunsaturated fatty acids from alpa-linolenic acid family, but when glucose was added to the medium, alpha-linolenic acid was preferably elongated rather than converted into eicose-pentaenoic acid. The ultrastructural study revealed HTC cells with a simple cytoplasmic organization, showing little evidence of their origin from hepatocytes. The cells cultured in a complete medium appeared well preserved and were similar to those \"fasted\" for 12 hours and \"refed\" for another 12 hours using Swim's 77 medium without serum. The amount of glucose in the medium plays a role in preserving the cell structure. This effect does not occur if glucose is added in the absence of aminoacids and vitamins.", "contents": "Effect of \"fasting\" and different concentrations of glucose on alpha-linolenic acid metabolism in HTC cells. Correlation with the ultrastructural study. HTC cells are able to convert alpha-linolenic acid into higher homologs by desaturating and elongating reactions. When the cells were cultured in a Krebs Ringer bicarbonate solution (\"fasted cells\") a decrease in both biosynthetic reactions took place. \"Refeeding\" the cells with Swim's 77 medium without glucose enhanced the biosynthesis of polyunsaturated fatty acids from alpa-linolenic acid family, but when glucose was added to the medium, alpha-linolenic acid was preferably elongated rather than converted into eicose-pentaenoic acid. The ultrastructural study revealed HTC cells with a simple cytoplasmic organization, showing little evidence of their origin from hepatocytes. The cells cultured in a complete medium appeared well preserved and were similar to those \"fasted\" for 12 hours and \"refed\" for another 12 hours using Swim's 77 medium without serum. The amount of glucose in the medium plays a role in preserving the cell structure. This effect does not occur if glucose is added in the absence of aminoacids and vitamins."}
{"id": "PMID:202862", "title": "Studies of poly(A+)-RNA in mouse hepatoma and cortisone-stimulated rat liver.", "content": "The content of poly(A)-containing RNA in subcellar fractions has been investigated both in cortisone-treated rat liver and experimental hepatoma cells. The fractions included nuclei, cytoplasm, mitochondria, free and membrane-bound polyribosomes. 1) In both cases of genome activation (cortisone induction and hepatoma cells) an increase in poly(A) content of all subcellular fractions except free polyribosomes was observed. 2) Cortisone was found to induce elongation of poly(A) segments detected in both nuclei and cytoplasm. 3) An increase in the poly(A) block size also was found to be stimulated in nuclei and cytoplasm of hepatoma cells. 4) The observed elongation in poly(A) length occurred against the background of an increase of the population of of poly(A)-RNA's.", "contents": "Studies of poly(A+)-RNA in mouse hepatoma and cortisone-stimulated rat liver. The content of poly(A)-containing RNA in subcellar fractions has been investigated both in cortisone-treated rat liver and experimental hepatoma cells. The fractions included nuclei, cytoplasm, mitochondria, free and membrane-bound polyribosomes. 1) In both cases of genome activation (cortisone induction and hepatoma cells) an increase in poly(A) content of all subcellular fractions except free polyribosomes was observed. 2) Cortisone was found to induce elongation of poly(A) segments detected in both nuclei and cytoplasm. 3) An increase in the poly(A) block size also was found to be stimulated in nuclei and cytoplasm of hepatoma cells. 4) The observed elongation in poly(A) length occurred against the background of an increase of the population of of poly(A)-RNA's."}
{"id": "PMID:202867", "title": "[Domiciliary assisted respiration by tracheotomy for chronic respiratory insufficiency (author's transl)].", "content": "Prerequisites for success in domiciliary assisted respiration for chronic respiratory insufficiency are the understanding of the patient and his active participation in the treatment as well as adjustment and attitude of his environment. The authors report their experience in 89 patients. Spirographic data were obtained in 72 patients which permitted subdivision into a group with restrictive disturbances and one with obstructive changes. The differences in prognosis in these two groups of patients were surprising. The survival rates in the obstructive diseases after 3, 5 and 10 years were 54%, 38% and 33% respectively; the corresponding values for the restrictive diseases were 84%, 84% and 69%. These differences are statistically significant. The restrictive changes are therefore considerably more favorable to assess, also with respect to a better quality of life.", "contents": "[Domiciliary assisted respiration by tracheotomy for chronic respiratory insufficiency (author's transl)]. Prerequisites for success in domiciliary assisted respiration for chronic respiratory insufficiency are the understanding of the patient and his active participation in the treatment as well as adjustment and attitude of his environment. The authors report their experience in 89 patients. Spirographic data were obtained in 72 patients which permitted subdivision into a group with restrictive disturbances and one with obstructive changes. The differences in prognosis in these two groups of patients were surprising. The survival rates in the obstructive diseases after 3, 5 and 10 years were 54%, 38% and 33% respectively; the corresponding values for the restrictive diseases were 84%, 84% and 69%. These differences are statistically significant. The restrictive changes are therefore considerably more favorable to assess, also with respect to a better quality of life."}
{"id": "PMID:202868", "title": "[Domiciliary assisted respiration in the Languedoc-Roussillon region (author's transl)].", "content": "The activities of the Society for Domiciliary Assisted Respiration founded in the Languedoc-Roussillon region in 1973 are reported. Up to September 30, 1976, 281 patients were treated, 189 are still alive. Obstructive chronic bronchopneumopathies were predominant. In the second place were restrictive respiratory insufficiences and respiratory muscle failure in the third. Obviously, careful attention by a specially trained doctor and nurse must be guaranteed, as well as technical support. Blood gas analyses and spirographic investigations control the course of treatment. Domiciliary assisted respiration not only prolongs the life of numerous patients, but also improves its quality.", "contents": "[Domiciliary assisted respiration in the Languedoc-Roussillon region (author's transl)]. The activities of the Society for Domiciliary Assisted Respiration founded in the Languedoc-Roussillon region in 1973 are reported. Up to September 30, 1976, 281 patients were treated, 189 are still alive. Obstructive chronic bronchopneumopathies were predominant. In the second place were restrictive respiratory insufficiences and respiratory muscle failure in the third. Obviously, careful attention by a specially trained doctor and nurse must be guaranteed, as well as technical support. Blood gas analyses and spirographic investigations control the course of treatment. Domiciliary assisted respiration not only prolongs the life of numerous patients, but also improves its quality."}
{"id": "PMID:202870", "title": "Molecular dosimetry of the mutagen ethyl methanesulfonate in Drosophila melanogaster spermatozoa: linear relation of DNA alkylation per sperm cell (dose) to sex-linked recessive lethals.", "content": "The dosage-response curve for EMS was determined with dose measured as ethylations of DNA per sperm cell, and response measured as the relative frequency of sex-linked recessive lethals induced in sperm cells of Drosophila melanogaster. Dose can be converted to ethylations per nucleotide of DNA by dividing ethylations of DNA per sperm cell by 3 X 10(8) nucleotides per sperm cell. Adult males were exposed to equal amounts of either [3H]EMS for determining dose or nonlabeled EMS for determining mutational response. By feeding EMS for 24 h in a concentration of 25 mM, a high dose of 1.4 X 10(-2) ethylations per nucleotide was observed. With 1.4% of the nucleotides ethylated, 57% of the X-chromosomes were hemizygously viable; therefore, ethylation per se is not very efficient in inducing mutations. The relative frequency of mutations increased linearly with the dose from a dose of 2.1 X 10(-4) to 1.4 X 10(-2) ethylations per nucleotide. No threshold was apparent, and the statistical limits of the exponent, 1.0 +/- 0.1, excluded an exponent as high as 1.2. This linear relation suggests no change in mechanism of mutagenesis occurs from low to high dose in Drosophila. A nonlinear relation was found between exposure and dose; when exposure was increased by a factor of 250 (from 0.1 to 25 mM EMS in the feeding medium) dose was increased by a factor of only 68. By extrapolating down from our lowest dose of 2.1 X 10(-4) ethylations per nucleotide with an observed frequency of 0.55% +/- 0.08% sex-linked recessive lethals, we estimate the doubling dose for sex-linked recessive lethals to be 4 X 10(-5) ethylations per nucleotide.", "contents": "Molecular dosimetry of the mutagen ethyl methanesulfonate in Drosophila melanogaster spermatozoa: linear relation of DNA alkylation per sperm cell (dose) to sex-linked recessive lethals. The dosage-response curve for EMS was determined with dose measured as ethylations of DNA per sperm cell, and response measured as the relative frequency of sex-linked recessive lethals induced in sperm cells of Drosophila melanogaster. Dose can be converted to ethylations per nucleotide of DNA by dividing ethylations of DNA per sperm cell by 3 X 10(8) nucleotides per sperm cell. Adult males were exposed to equal amounts of either [3H]EMS for determining dose or nonlabeled EMS for determining mutational response. By feeding EMS for 24 h in a concentration of 25 mM, a high dose of 1.4 X 10(-2) ethylations per nucleotide was observed. With 1.4% of the nucleotides ethylated, 57% of the X-chromosomes were hemizygously viable; therefore, ethylation per se is not very efficient in inducing mutations. The relative frequency of mutations increased linearly with the dose from a dose of 2.1 X 10(-4) to 1.4 X 10(-2) ethylations per nucleotide. No threshold was apparent, and the statistical limits of the exponent, 1.0 +/- 0.1, excluded an exponent as high as 1.2. This linear relation suggests no change in mechanism of mutagenesis occurs from low to high dose in Drosophila. A nonlinear relation was found between exposure and dose; when exposure was increased by a factor of 250 (from 0.1 to 25 mM EMS in the feeding medium) dose was increased by a factor of only 68. By extrapolating down from our lowest dose of 2.1 X 10(-4) ethylations per nucleotide with an observed frequency of 0.55% +/- 0.08% sex-linked recessive lethals, we estimate the doubling dose for sex-linked recessive lethals to be 4 X 10(-5) ethylations per nucleotide."}
{"id": "PMID:202873", "title": "Tumour-specific phenylalanine tRNA contains two supernumerary methylated bases.", "content": "Every malignant tumour examined contains aberrant tRNA methyltransferases and a few tRNAs which are absent from the normal tissue of origin. To determine whether tumour-specific tRNAs have different modifications from those in normal tissue, we purified the most frequently occurring tumour-specific isoaccepting tRNA from two malignant tissues. The isoaccepting phenylalanine tRNA from Novikoff hepatoma and Ehrlich ascites cells both contain two supernumerary methylated bases. One of these l-methylguanine, is absent from the phenylalanine tRNA of normal rat, mouse, rabbit and calf liver. An increase in the levels of 5-methylcytidine and dihydrouridine was also detected.", "contents": "Tumour-specific phenylalanine tRNA contains two supernumerary methylated bases. Every malignant tumour examined contains aberrant tRNA methyltransferases and a few tRNAs which are absent from the normal tissue of origin. To determine whether tumour-specific tRNAs have different modifications from those in normal tissue, we purified the most frequently occurring tumour-specific isoaccepting tRNA from two malignant tissues. The isoaccepting phenylalanine tRNA from Novikoff hepatoma and Ehrlich ascites cells both contain two supernumerary methylated bases. One of these l-methylguanine, is absent from the phenylalanine tRNA of normal rat, mouse, rabbit and calf liver. An increase in the levels of 5-methylcytidine and dihydrouridine was also detected."}
{"id": "PMID:202880", "title": "Rotational behaviour and cGMP responses following manipulation of nigral mechanisms with chlordiazepoxide. Evidence for enhancement of GABA transmission by benzodiazepines.", "content": "Unilateral stereotaxic injections of 1 microgram of the soluble benzodiazepine chlordiazepoxide hydrochloride into the predominantly GABA-containing zona reticulata of the substantia nigra of amphetamine-pretreated rats induced rotational behaviour similar to that seen following unilateral elevation of nigral GABA levels and amphetamine treatment; this effect was not seen following injections into the vicinity of the predominantly dopamine-containing zona compacta. Chlordiazepoxide-induced rotations were abolished by the GABA-antagonist picrotoxin. Both chlordiazepoxide and GABA depressed production of cyclic 3',5'-guanosine monophosphate in samples of nigral tissue in vitro as estimated by radioimmunoassay. It is concluded that chlordiazepoxide may enhance GABA transmission within the substantia nigra, by some as yet unidentified mechanism, to create asymmetric activity in GABA-modulated neurones and hence induce rotation.", "contents": "Rotational behaviour and cGMP responses following manipulation of nigral mechanisms with chlordiazepoxide. Evidence for enhancement of GABA transmission by benzodiazepines. Unilateral stereotaxic injections of 1 microgram of the soluble benzodiazepine chlordiazepoxide hydrochloride into the predominantly GABA-containing zona reticulata of the substantia nigra of amphetamine-pretreated rats induced rotational behaviour similar to that seen following unilateral elevation of nigral GABA levels and amphetamine treatment; this effect was not seen following injections into the vicinity of the predominantly dopamine-containing zona compacta. Chlordiazepoxide-induced rotations were abolished by the GABA-antagonist picrotoxin. Both chlordiazepoxide and GABA depressed production of cyclic 3',5'-guanosine monophosphate in samples of nigral tissue in vitro as estimated by radioimmunoassay. It is concluded that chlordiazepoxide may enhance GABA transmission within the substantia nigra, by some as yet unidentified mechanism, to create asymmetric activity in GABA-modulated neurones and hence induce rotation."}
{"id": "PMID:202882", "title": "Monoamine oxidase in rat reticulocytes: subcellular localization and identification of isoenzymes.", "content": "After \"chemically induced reticulocytosis\" in rats by treatment with acetyl-phenylhydrazide, monoamine oxidase (MAO) activities were determined in erythrocyte preparations of these animals. Studies on subcellular fractions obtained by differential centrifugation showed that the enzyme activity of rat reticulocytes is a classical mitochondrial MAO. The patterns of inhibition produced by clorgyline (A-type MAO), deprenil (B-type MAO) and pargyline or tranylcypromine (both types of MAO) in reticulocytes were determined in vitro using tryptamine as a substrate for both types of MAO and phenylethylamine as a substrate for the B-type. The results indicate that both A-type (approximately 75%) and B-type (approximately 25%) MAO are present in rat reticulocytes; while tryptamine was mainly deaminated by the A-type enzyme, both types of MAO were shown to contribute to the deamination of phenylethylamine. These findings were confirmed in investigations on the thermostabilities of the tryptamine and phenylethylamine deaminating activities of rat reticulocyte MAO.", "contents": "Monoamine oxidase in rat reticulocytes: subcellular localization and identification of isoenzymes. After \"chemically induced reticulocytosis\" in rats by treatment with acetyl-phenylhydrazide, monoamine oxidase (MAO) activities were determined in erythrocyte preparations of these animals. Studies on subcellular fractions obtained by differential centrifugation showed that the enzyme activity of rat reticulocytes is a classical mitochondrial MAO. The patterns of inhibition produced by clorgyline (A-type MAO), deprenil (B-type MAO) and pargyline or tranylcypromine (both types of MAO) in reticulocytes were determined in vitro using tryptamine as a substrate for both types of MAO and phenylethylamine as a substrate for the B-type. The results indicate that both A-type (approximately 75%) and B-type (approximately 25%) MAO are present in rat reticulocytes; while tryptamine was mainly deaminated by the A-type enzyme, both types of MAO were shown to contribute to the deamination of phenylethylamine. These findings were confirmed in investigations on the thermostabilities of the tryptamine and phenylethylamine deaminating activities of rat reticulocyte MAO."}
{"id": "PMID:202883", "title": "Correlation between drug-induced supersensitivity of dopamine dependent striatal mechanisms and the increase in striatal content of the Ca2+ regulated protein activator of cAMP phosphodiesterase.", "content": "Rats were injected daily with 1.3 mumol/kg of haloperidol s.c. for 10 days. From the second to the ninth day after haloperidol withdrawal the rats developed supersensitivity to the behavioral affects of apomorphine. Concomitantly, the Ka of dopamine for the activation of striatal adenylate cyclase was lowered and the striatal content of the Ca2+ dependent protein that activates cAMP phosphodiesterase was increased. This activator protein is stored in striatal membranes and can be released by membrane phosphorylation in cytosol. This protein increases the activity of the high Km phosphodiesterase (Uzunov et al., 1976) but when it is bound to striatal membranes it facilitates the activation of striatal adenylate cyclase by dopamine (Gnegy et al., 1976b). The increase in protein activator content of striatal membranes caused by haloperidol could be a primary factor in causing supersensitivity to the biochemical and behavioral effects of dopamine receptor agonists.", "contents": "Correlation between drug-induced supersensitivity of dopamine dependent striatal mechanisms and the increase in striatal content of the Ca2+ regulated protein activator of cAMP phosphodiesterase. Rats were injected daily with 1.3 mumol/kg of haloperidol s.c. for 10 days. From the second to the ninth day after haloperidol withdrawal the rats developed supersensitivity to the behavioral affects of apomorphine. Concomitantly, the Ka of dopamine for the activation of striatal adenylate cyclase was lowered and the striatal content of the Ca2+ dependent protein that activates cAMP phosphodiesterase was increased. This activator protein is stored in striatal membranes and can be released by membrane phosphorylation in cytosol. This protein increases the activity of the high Km phosphodiesterase (Uzunov et al., 1976) but when it is bound to striatal membranes it facilitates the activation of striatal adenylate cyclase by dopamine (Gnegy et al., 1976b). The increase in protein activator content of striatal membranes caused by haloperidol could be a primary factor in causing supersensitivity to the biochemical and behavioral effects of dopamine receptor agonists."}
{"id": "PMID:202884", "title": "Effects of guanidine on synaptic transmission in the spinal cord of the frog.", "content": "The effects of guanidine on motoneurons of the isolated frog spinal cord were studied by adding the drug to the solution bathing the cord during intracellular recording. Guanidine (5.10(-4) M) did not alter the membrane potential of motoneurons. The main effect was a marked increase of the amplitudes and frequencies of small spontaneously occurring inhibitory postsynaptic potentials. The hyperpolarizing component of postsynaptic potentials evoked by stimulation of dorsal roots was also enhanced by guanidine. Higher concentrations of guanidine (5.10(-3) M) resulted in a very large and irreversible increase of the small spontaneously occurring inhibitory potentials, which now appeared in a regular, rhythmic pattern. The effects of guanidine could easily be blocked by increasing the magnesium ions (15 mM) in the bath solution. These results indicate that guanidine facilitates the release of an inhibitory transmitter in afferent terminals of the frog spinal cord either by a direct action on these terminals or indirectly by an action on nerve endings impinging on inhibitory interneurons.", "contents": "Effects of guanidine on synaptic transmission in the spinal cord of the frog. The effects of guanidine on motoneurons of the isolated frog spinal cord were studied by adding the drug to the solution bathing the cord during intracellular recording. Guanidine (5.10(-4) M) did not alter the membrane potential of motoneurons. The main effect was a marked increase of the amplitudes and frequencies of small spontaneously occurring inhibitory postsynaptic potentials. The hyperpolarizing component of postsynaptic potentials evoked by stimulation of dorsal roots was also enhanced by guanidine. Higher concentrations of guanidine (5.10(-3) M) resulted in a very large and irreversible increase of the small spontaneously occurring inhibitory potentials, which now appeared in a regular, rhythmic pattern. The effects of guanidine could easily be blocked by increasing the magnesium ions (15 mM) in the bath solution. These results indicate that guanidine facilitates the release of an inhibitory transmitter in afferent terminals of the frog spinal cord either by a direct action on these terminals or indirectly by an action on nerve endings impinging on inhibitory interneurons."}
{"id": "PMID:202886", "title": "Disturbances in kidney functions and calcium and phosphate metabolism in cadmium-poisoned rats.", "content": "In an attempt to elucidate the etiology and pathogenesis of 'Itai-Itai' disease, the relationship between bone and kidney lesions in cadmium-poisoned rats was determined using the standard renal clearance technique. Calcium and cadmium contents in the femur and kidney were also estimated. The severity of renal lesions was histologically evident both in the tubule and glomerulus, and paralleled the decrease in GFR and the increase in FF. There was no significant change in fractional excretion of phosphate, but fractional excretion of calcium increased in the cadmium-poisoned rats. The secondary hyperparathyroidism followed by uremic renal osteodystrophy did not result in an osteomalacia. Thus, it is apparent that disturbance in calcium reabsorption in the tubules plays a role in the loss of calcium, and cadmium associated with low levels of calcium has a direct effect on the bone-causing osteomalacia.", "contents": "Disturbances in kidney functions and calcium and phosphate metabolism in cadmium-poisoned rats. In an attempt to elucidate the etiology and pathogenesis of 'Itai-Itai' disease, the relationship between bone and kidney lesions in cadmium-poisoned rats was determined using the standard renal clearance technique. Calcium and cadmium contents in the femur and kidney were also estimated. The severity of renal lesions was histologically evident both in the tubule and glomerulus, and paralleled the decrease in GFR and the increase in FF. There was no significant change in fractional excretion of phosphate, but fractional excretion of calcium increased in the cadmium-poisoned rats. The secondary hyperparathyroidism followed by uremic renal osteodystrophy did not result in an osteomalacia. Thus, it is apparent that disturbance in calcium reabsorption in the tubules plays a role in the loss of calcium, and cadmium associated with low levels of calcium has a direct effect on the bone-causing osteomalacia."}
{"id": "PMID:202888", "title": "Influence of lysine vasopressin on the EEG in man. Preliminary results.", "content": "The aim of the present study was to determine the influence of lysine vasopressin on the electroencephalogram in man. Our results suggest a dose-dependent activity of lysine vasopressin on the EEG, which might be similar to that observed in animal and man after administration of nicotine. This effect seems to be independent of the action of the corticotropic hormone simultaneously released.", "contents": "Influence of lysine vasopressin on the EEG in man. Preliminary results. The aim of the present study was to determine the influence of lysine vasopressin on the electroencephalogram in man. Our results suggest a dose-dependent activity of lysine vasopressin on the EEG, which might be similar to that observed in animal and man after administration of nicotine. This effect seems to be independent of the action of the corticotropic hormone simultaneously released."}
{"id": "PMID:202889", "title": "Cell-mediated immunity to measles virus in multiple sclerosis: correlation with disability.", "content": "The blastogenic transformation of lymphocytes on exposure to antigen was used to investigate cell-mediated immune responses to viruses implicated in the pathogenesis of multiple sclerosis. In 12 patients with \"early\" multiple sclerosis, lymphocyte reactivity to measles virus, parainfluenza virus, and vaccinia virus did not differ significantly from reactivity in a healthy control group. However, there was a significant inverse correlation between the lymphocyte blastogenic response to measles and vaccinia viruses and the predetermined degree of disability from multiple sclerosis. A deficient cellular response to measles virus, and possibly to other common viruses, is therefore probably a consequence of the disease itself, and not a causal factor.", "contents": "Cell-mediated immunity to measles virus in multiple sclerosis: correlation with disability. The blastogenic transformation of lymphocytes on exposure to antigen was used to investigate cell-mediated immune responses to viruses implicated in the pathogenesis of multiple sclerosis. In 12 patients with \"early\" multiple sclerosis, lymphocyte reactivity to measles virus, parainfluenza virus, and vaccinia virus did not differ significantly from reactivity in a healthy control group. However, there was a significant inverse correlation between the lymphocyte blastogenic response to measles and vaccinia viruses and the predetermined degree of disability from multiple sclerosis. A deficient cellular response to measles virus, and possibly to other common viruses, is therefore probably a consequence of the disease itself, and not a causal factor."}
{"id": "PMID:202893", "title": "[Value of electromyography for the detection of peripheral neuropathies in the course of chronic hepatopathies].", "content": "It has recently been noted that peripheral nerve fibres are involved in the course of chronic liver disease. The existence of hepatic polyneuropathy is still a matter of debate. A series of 29 subjects (not including diabetics or alcoholics) were examined clinically and electromyographically. Signs of distal lower extremity polyneuritis (paresthesia, hypoesthesia and osteotendinous hypo-areflexia) were noted in 31%. Latent neuropathy was observed in the form of slow maximum and minimum motor conduction rates in clinically unimpaired nerves. Electromyographical alterations were more evident in subjects with frankly chronic as opposed to barely chronic liver disease.", "contents": "[Value of electromyography for the detection of peripheral neuropathies in the course of chronic hepatopathies]. It has recently been noted that peripheral nerve fibres are involved in the course of chronic liver disease. The existence of hepatic polyneuropathy is still a matter of debate. A series of 29 subjects (not including diabetics or alcoholics) were examined clinically and electromyographically. Signs of distal lower extremity polyneuritis (paresthesia, hypoesthesia and osteotendinous hypo-areflexia) were noted in 31%. Latent neuropathy was observed in the form of slow maximum and minimum motor conduction rates in clinically unimpaired nerves. Electromyographical alterations were more evident in subjects with frankly chronic as opposed to barely chronic liver disease."}
{"id": "PMID:202894", "title": "[Cephalic zoster with involvement of the 5th, 7th, 8th, 9th and 10th cranial nerves].", "content": "A case of cephalic zoster with involvement of the 5th, 7th, 8th, 9th and 10th left cranial nerves is described. The anatomopathological findings are surveyed. These show that lesions are often found in several areas of the nervous system. The pathogenesis of these forms is examined, with particular reference to the mechanism of involvement of several cranial nerves. It is felt that this is primarily due to reactivation of the virus in several ganglia.", "contents": "[Cephalic zoster with involvement of the 5th, 7th, 8th, 9th and 10th cranial nerves]. A case of cephalic zoster with involvement of the 5th, 7th, 8th, 9th and 10th left cranial nerves is described. The anatomopathological findings are surveyed. These show that lesions are often found in several areas of the nervous system. The pathogenesis of these forms is examined, with particular reference to the mechanism of involvement of several cranial nerves. It is felt that this is primarily due to reactivation of the virus in several ganglia."}
{"id": "PMID:202896", "title": "Mercury levels in residents of a geothermal area in the Central North Island.", "content": "As a result of previous high trace metal findings in the soil, cattle, vegetation and water of the Broadlands area of New Zealand a study was made of the levels of mercury, selenium, arsenic and zinc in a group of children from this region. Arsenic and zinc levels were found to be normal but significantly raised urinary spot mercury concentrations were found in some of the children when studied in December 1975 and 24 hour urinary mercury concentrations recorded six months later were also raised, but to a lesser degree. Samples of household tap water showed increased mercury concentrations (median 0.001 micromol/L). In agreement with other New Zealand studies the blood selenium concentrations were low (76.7 mu/L) and they did not vary in relation to urinary mercury levels. The children were also examined for signs of peripheral neuropathy but only minor abnormalities were found. The source of the elevated mercury is uncertain but it may come from drinking water or possibly from locally produced meat or vegetables.", "contents": "Mercury levels in residents of a geothermal area in the Central North Island. As a result of previous high trace metal findings in the soil, cattle, vegetation and water of the Broadlands area of New Zealand a study was made of the levels of mercury, selenium, arsenic and zinc in a group of children from this region. Arsenic and zinc levels were found to be normal but significantly raised urinary spot mercury concentrations were found in some of the children when studied in December 1975 and 24 hour urinary mercury concentrations recorded six months later were also raised, but to a lesser degree. Samples of household tap water showed increased mercury concentrations (median 0.001 micromol/L). In agreement with other New Zealand studies the blood selenium concentrations were low (76.7 mu/L) and they did not vary in relation to urinary mercury levels. The children were also examined for signs of peripheral neuropathy but only minor abnormalities were found. The source of the elevated mercury is uncertain but it may come from drinking water or possibly from locally produced meat or vegetables."}
{"id": "PMID:202897", "title": "Genital herpes and the FTA-ABS.", "content": "The fluorescent treponemal antibody-absorption test (FTA-ABS) was obtained on a series of 55 healthy men and women with documented recurrent genital herpes. In contrast to a previous report indicating that a significant number of these patients demonstrated a false positive FTA-ABS, the present series failed to confirm these findings. Of interest, however, was the high incidence of borderline FTA-ABS tests seen in both the control group and the group with herpes. The significance and use of the FTA-ABS are briefly discussed.", "contents": "Genital herpes and the FTA-ABS. The fluorescent treponemal antibody-absorption test (FTA-ABS) was obtained on a series of 55 healthy men and women with documented recurrent genital herpes. In contrast to a previous report indicating that a significant number of these patients demonstrated a false positive FTA-ABS, the present series failed to confirm these findings. Of interest, however, was the high incidence of borderline FTA-ABS tests seen in both the control group and the group with herpes. The significance and use of the FTA-ABS are briefly discussed."}
{"id": "PMID:202898", "title": "Origin of estrogen in isosexual precocious pseudopuberty due to a granulosa-theca cell tumor.", "content": "The purpose of the present study was to quantify the rates of production and to define the mechanism(s) or origin of sex steroid hormones in a 3 1/2-year-old girl with isosexual precocious pseudopuberty caused by a granulosa-theca cell tumor of the ovary. The results suggest that the hyperestrogenism occurs principally due to the secretion of estradiol-17beta synthesized de novo by the tumor, but that the tumor in vivo was also capable of aromatizing C19 plasma precursor hormones to estrogen.", "contents": "Origin of estrogen in isosexual precocious pseudopuberty due to a granulosa-theca cell tumor. The purpose of the present study was to quantify the rates of production and to define the mechanism(s) or origin of sex steroid hormones in a 3 1/2-year-old girl with isosexual precocious pseudopuberty caused by a granulosa-theca cell tumor of the ovary. The results suggest that the hyperestrogenism occurs principally due to the secretion of estradiol-17beta synthesized de novo by the tumor, but that the tumor in vivo was also capable of aromatizing C19 plasma precursor hormones to estrogen."}
{"id": "PMID:202901", "title": "Basement membrane changes under neoplastic oral mucous membrane. Ultrastructural observations, review of the literature, and a unifying concept.", "content": "This study explores the morphologic nature of the basement membrane under neoplastic oral mucous membrane. Of particular interest is the progression of changes associated with dysplasia, carcinoma in situ, and invasive carcinoma. On the basis of a critical review of the literature and our own ultrastructural observations, we present a unifying concept for the development of these basement membrane changes. This concept proposes that neoplastic epithelial cells may produce a collagenolytic enzyme which is released into the epithelial intercellular spaces. This enzyme permeates to the basement membrane, causes breaks in the basement membrane, and focal loss of stromal area contiguous with intercellular spaces. The neoplastic basal cells develop pseudopodia that eventually extend through the breaks in the basement membrane. This concept suggests that the basement membrane changes herald the progression of carcinoma in situ to invasive carcinoma.", "contents": "Basement membrane changes under neoplastic oral mucous membrane. Ultrastructural observations, review of the literature, and a unifying concept. This study explores the morphologic nature of the basement membrane under neoplastic oral mucous membrane. Of particular interest is the progression of changes associated with dysplasia, carcinoma in situ, and invasive carcinoma. On the basis of a critical review of the literature and our own ultrastructural observations, we present a unifying concept for the development of these basement membrane changes. This concept proposes that neoplastic epithelial cells may produce a collagenolytic enzyme which is released into the epithelial intercellular spaces. This enzyme permeates to the basement membrane, causes breaks in the basement membrane, and focal loss of stromal area contiguous with intercellular spaces. The neoplastic basal cells develop pseudopodia that eventually extend through the breaks in the basement membrane. This concept suggests that the basement membrane changes herald the progression of carcinoma in situ to invasive carcinoma."}
{"id": "PMID:202902", "title": "In vitro comparison of sialographic agents.", "content": "An experimental model is presented for in vitro comparative evaluation of radiopaque media. Experimental results parallel the clinical picture of fractionated filling films and comparative radiodensity of oil- and water-soluble media.", "contents": "In vitro comparison of sialographic agents. An experimental model is presented for in vitro comparative evaluation of radiopaque media. Experimental results parallel the clinical picture of fractionated filling films and comparative radiodensity of oil- and water-soluble media."}
{"id": "PMID:202906", "title": "[Therapy of inoperable bronchial carcinoma].", "content": "The results of a prospective randomized study on carcinoma of the bronchus are reported. In a total of 56 patients polychemotherapy, high-dosage vitamin-A treatment, Endoxan and immunotherapy, as well as the application of proteolytic enzymes in altogether 5 combinations of therapy were tested.", "contents": "[Therapy of inoperable bronchial carcinoma]. The results of a prospective randomized study on carcinoma of the bronchus are reported. In a total of 56 patients polychemotherapy, high-dosage vitamin-A treatment, Endoxan and immunotherapy, as well as the application of proteolytic enzymes in altogether 5 combinations of therapy were tested."}
{"id": "PMID:202910", "title": "[Action of calcitonin on osteoclasts in Paget's bone disease during long term treatment (author's transl)].", "content": "Comparison of biopsies from patients with Paget's bone disease before and during long-term treatment with calcitonin reveals that the ration of bone-adherent osteoclasts to free osteoclasts is not modified by the hormone. Nor does treatment alter the average number of nuclei in osteoclasts. Under electron microscopy, all the cytological anomalies of osteoclasts in Paget's bone disease and, in particular, the characteristic nuclear inclusions, persist through treatment. Thus, although such osteoclasts do react to calcitonin as demonstrated by several authors, the specific morphological anomalies remain unaffected by the treatment. It is likely that the osteoclast in Paget's bone disease is an abnormal cell with peculiarities which may be related to the yet unknown etiology of the disease.", "contents": "[Action of calcitonin on osteoclasts in Paget's bone disease during long term treatment (author's transl)]. Comparison of biopsies from patients with Paget's bone disease before and during long-term treatment with calcitonin reveals that the ration of bone-adherent osteoclasts to free osteoclasts is not modified by the hormone. Nor does treatment alter the average number of nuclei in osteoclasts. Under electron microscopy, all the cytological anomalies of osteoclasts in Paget's bone disease and, in particular, the characteristic nuclear inclusions, persist through treatment. Thus, although such osteoclasts do react to calcitonin as demonstrated by several authors, the specific morphological anomalies remain unaffected by the treatment. It is likely that the osteoclast in Paget's bone disease is an abnormal cell with peculiarities which may be related to the yet unknown etiology of the disease."}
{"id": "PMID:202913", "title": "Pituitary adenomas.", "content": "Pituitary adenomas arise from and consist of adenohypophyseal cells. Based on the tinctorial characteristics of the cell cytoplasm, they were divided previously into chromophobic, acidophilic, and basophilic adenoma types. This classification is only of limited value, since it fails to consider the endocrine function of the adenoma cells and the cell type from which the tumor originates. Advanced morphologic techniques, including electron microscopy and immunocytology, led to a new pituitary adenoma classification reflecting current knowledge and attributing greater significance to clinical features, structure-function relationships, and cytogenesis. The morphologic study of pituitary adenomas is still in a relatively early stage and much more work is required to understand the basic principles of pituitary cytopathology. Thus, the classification used in this review may change as new facts accumulate. We feel justified to say that attempts to correlate structural features of pituitary adenomas with secretory activity and their separation into distinct entities cannot be regarded as examples of curiosity-oriented research. This type of investigation represents not only an intellectually rewarding experience, but is also of practical value and provides important information for the endocrinologists.", "contents": "Pituitary adenomas. Pituitary adenomas arise from and consist of adenohypophyseal cells. Based on the tinctorial characteristics of the cell cytoplasm, they were divided previously into chromophobic, acidophilic, and basophilic adenoma types. This classification is only of limited value, since it fails to consider the endocrine function of the adenoma cells and the cell type from which the tumor originates. Advanced morphologic techniques, including electron microscopy and immunocytology, led to a new pituitary adenoma classification reflecting current knowledge and attributing greater significance to clinical features, structure-function relationships, and cytogenesis. The morphologic study of pituitary adenomas is still in a relatively early stage and much more work is required to understand the basic principles of pituitary cytopathology. Thus, the classification used in this review may change as new facts accumulate. We feel justified to say that attempts to correlate structural features of pituitary adenomas with secretory activity and their separation into distinct entities cannot be regarded as examples of curiosity-oriented research. This type of investigation represents not only an intellectually rewarding experience, but is also of practical value and provides important information for the endocrinologists."}
{"id": "PMID:202915", "title": "Application of a live varicella vaccine in children with acute leukemia or other malignant diseases.", "content": "A live varicella vaccine was used in 11 susceptible children in remission from acute leukemia, ten of whom had been in remission for six months or less, and in 6 children with neuroblastoma and retinoblastoma. In the immunological checkup before vaccination, most of them showed a positive reaction in the skin tests with dinitrochlorobenzene, phytohemagglutinin, purified protein derivative, and viral antigens. Leukopenia (three cases, less than 3,000/cu mm) and decreased IgG level (two cases, 380 mg/dl and 445 mg/dl) were observed in the children with leukemia. Anticancer medication was suspended from one week before vaccination to one week after vaccination. The only clinical reaction was a minute rash that appeared three weeks after vaccination in two children with leukemia and that disappeared within three days. Serological responses by complement fixing and neutralizing (NT) tests were detected in all the vaccinated children four weeks after vaccination, and NT antibody was still detected 28 months after vaccination in the two patients tested. Three of the vaccines were exposed to natural varicella at home and in the classroom 2 to 18 months after vaccination, but they were free from any varicella symptoms.", "contents": "Application of a live varicella vaccine in children with acute leukemia or other malignant diseases. A live varicella vaccine was used in 11 susceptible children in remission from acute leukemia, ten of whom had been in remission for six months or less, and in 6 children with neuroblastoma and retinoblastoma. In the immunological checkup before vaccination, most of them showed a positive reaction in the skin tests with dinitrochlorobenzene, phytohemagglutinin, purified protein derivative, and viral antigens. Leukopenia (three cases, less than 3,000/cu mm) and decreased IgG level (two cases, 380 mg/dl and 445 mg/dl) were observed in the children with leukemia. Anticancer medication was suspended from one week before vaccination to one week after vaccination. The only clinical reaction was a minute rash that appeared three weeks after vaccination in two children with leukemia and that disappeared within three days. Serological responses by complement fixing and neutralizing (NT) tests were detected in all the vaccinated children four weeks after vaccination, and NT antibody was still detected 28 months after vaccination in the two patients tested. Three of the vaccines were exposed to natural varicella at home and in the classroom 2 to 18 months after vaccination, but they were free from any varicella symptoms."}
{"id": "PMID:202916", "title": "Clinical and serologic testing of a live varicella vaccine and two-year follow-up for immunity of the vaccinated children.", "content": "A live varicella vaccine derived from the Oka strain was given on 181 children who had no history of varicella and were seronegative by complement fixation (CF) and neutralization (NT) tests; 125 children were hospitalized and 54 were receiving steroid therapy. Overall, seroconversion was achieved in 85.1% of the children by the CF test and in 97.8% by the NT test. Clinical reaction consisting of mild fever and rash appeared in only two children. One hundred seventy-nine of the vaccinated children were followed up by questionnaire and 51 were followed up serologically approximately two years later, at which time 10 of 51 (19.6%) were seropositive by the CF test and 50 of 51 (98.0%) by the NT test. Only one out of 80 children who had postvaccinal contact with varicella contracted mild varicella 16 months after vaccination. None of the vaccinees developed herpes zoster. These results suggest that this live varicella vaccine may safely and effectively be used for children with or without underlying diseases, including those receiving steroid therapy, and that immunity of at least two years' duration is conferred upon the vaccinated subjects.", "contents": "Clinical and serologic testing of a live varicella vaccine and two-year follow-up for immunity of the vaccinated children. A live varicella vaccine derived from the Oka strain was given on 181 children who had no history of varicella and were seronegative by complement fixation (CF) and neutralization (NT) tests; 125 children were hospitalized and 54 were receiving steroid therapy. Overall, seroconversion was achieved in 85.1% of the children by the CF test and in 97.8% by the NT test. Clinical reaction consisting of mild fever and rash appeared in only two children. One hundred seventy-nine of the vaccinated children were followed up by questionnaire and 51 were followed up serologically approximately two years later, at which time 10 of 51 (19.6%) were seropositive by the CF test and 50 of 51 (98.0%) by the NT test. Only one out of 80 children who had postvaccinal contact with varicella contracted mild varicella 16 months after vaccination. None of the vaccinees developed herpes zoster. These results suggest that this live varicella vaccine may safely and effectively be used for children with or without underlying diseases, including those receiving steroid therapy, and that immunity of at least two years' duration is conferred upon the vaccinated subjects."}
{"id": "PMID:202917", "title": "Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue.", "content": "A patient is described with subacute necrotizing encephalomyelopathy proven by autopsy. A slight increase of blood pyruvate and lactate levels with an increased lactate/pyruvate ratio and frequently increased beta-hydroxybutyrate/acetoacetate ratio suggested a disorder of mitochondrial oxidation. A cytochrome c oxidase deficiency was shown in peripheral muscle tissue with some residual cytochrome c oxidase activity in heart muscle. Normal cytochrome c oxidase activity was present in liver tissue. Because of the markedly higher levels of pyruvate and lactate in CSF compared with blood and an increased lactate/pyruvate ratio in CSF, there may also have been defective activity of cytochrome c oxidase in brain tissue. After a period of apparently normal development, the child's clinical condition gradually deteriorated and she died at age 6 years due to respiratory insufficiency. This study illustrates the fact that Leigh's disease is not linked to a single inherited molecular defect.", "contents": "Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue. A patient is described with subacute necrotizing encephalomyelopathy proven by autopsy. A slight increase of blood pyruvate and lactate levels with an increased lactate/pyruvate ratio and frequently increased beta-hydroxybutyrate/acetoacetate ratio suggested a disorder of mitochondrial oxidation. A cytochrome c oxidase deficiency was shown in peripheral muscle tissue with some residual cytochrome c oxidase activity in heart muscle. Normal cytochrome c oxidase activity was present in liver tissue. Because of the markedly higher levels of pyruvate and lactate in CSF compared with blood and an increased lactate/pyruvate ratio in CSF, there may also have been defective activity of cytochrome c oxidase in brain tissue. After a period of apparently normal development, the child's clinical condition gradually deteriorated and she died at age 6 years due to respiratory insufficiency. This study illustrates the fact that Leigh's disease is not linked to a single inherited molecular defect."}
{"id": "PMID:202919", "title": "Sodium pump stimulation by oxytocin and cyclic AMP in the isolated epithelium of the frog skin.", "content": "Activity of the Na pump was judged by Na extrusion in epithelial cells loaded with Na by a previous incubation in K-free solutions in the cold. Oxytocin significantly stimulated Na extrusion either at normal (3.5 mM) or low (0.25 mM) K in the medium. It was stimulated as well by cyclic AMP. Maximal concentrations of either agent caused about the same degree of stimulation. Addition of ouabain or removal of K prevented the action of both agents, but amiloride showed no effect at all. These results strongly suggest that, a) neurohypophyseal hormones not only increase Na entry across the mucosal barrier of the epithelium but they also stimulate the serosal Na pump, b) cyclic AMP not only mediates the action of neurohypophyseal hormones on Na and water permeability of the mucosal barrier, but it also mediates the action of the hormones on the Na pump of the serosal barrier.", "contents": "Sodium pump stimulation by oxytocin and cyclic AMP in the isolated epithelium of the frog skin. Activity of the Na pump was judged by Na extrusion in epithelial cells loaded with Na by a previous incubation in K-free solutions in the cold. Oxytocin significantly stimulated Na extrusion either at normal (3.5 mM) or low (0.25 mM) K in the medium. It was stimulated as well by cyclic AMP. Maximal concentrations of either agent caused about the same degree of stimulation. Addition of ouabain or removal of K prevented the action of both agents, but amiloride showed no effect at all. These results strongly suggest that, a) neurohypophyseal hormones not only increase Na entry across the mucosal barrier of the epithelium but they also stimulate the serosal Na pump, b) cyclic AMP not only mediates the action of neurohypophyseal hormones on Na and water permeability of the mucosal barrier, but it also mediates the action of the hormones on the Na pump of the serosal barrier."}
{"id": "PMID:202923", "title": "[Moschowitz's disease: efficacy of anti-platelet aggregation agents].", "content": "In November 1976, a 52 year old woman presented with a Moschowitz syndrome with clinical manifestations of continuous fever at 39 degrees and a transient Wernicke type aphasia. Laboratory findings included schizocytosis, a peripheral thrombocytopaenia and functional renal insufficiency. The ethanol tests was positive but there was no frank defibrination syndrome. After corticosteroid therapy failed, the patient was treated with Dipyridamole 400 mg/24 hours IV and acetylsalicylic acid 4 g/24 hours IV. Fever disappeared on the same day and the thrombocytopaenia was corrected in 48 hours. The patient was considered to be cured 15 days later. No precise aetiology to explain the Moschowitz syndrome was discovered apart from the recent ingestion of oestrogens. The authors emphasise the considerable progress which this use of a combination of Dipyridamole and aspirin represents, resulting in the cure of Moschowitz syndrome, a condition considered to be fatal up until a few years ago.", "contents": "[Moschowitz's disease: efficacy of anti-platelet aggregation agents]. In November 1976, a 52 year old woman presented with a Moschowitz syndrome with clinical manifestations of continuous fever at 39 degrees and a transient Wernicke type aphasia. Laboratory findings included schizocytosis, a peripheral thrombocytopaenia and functional renal insufficiency. The ethanol tests was positive but there was no frank defibrination syndrome. After corticosteroid therapy failed, the patient was treated with Dipyridamole 400 mg/24 hours IV and acetylsalicylic acid 4 g/24 hours IV. Fever disappeared on the same day and the thrombocytopaenia was corrected in 48 hours. The patient was considered to be cured 15 days later. No precise aetiology to explain the Moschowitz syndrome was discovered apart from the recent ingestion of oestrogens. The authors emphasise the considerable progress which this use of a combination of Dipyridamole and aspirin represents, resulting in the cure of Moschowitz syndrome, a condition considered to be fatal up until a few years ago."}
{"id": "PMID:202924", "title": "[The identification of hepatitis A virus in faeces. Diagnosis and epidemiological value (author's transl)].", "content": "During 1976, two hepatitis A epidemics in institutions enabled the authors to study the presence of the virus in the faeces during the course of the disease. After concentration of feacal extracts in polyethyleneglycol 6000, virions were observed by immune electron microscopy. Among 13 stool extracts examined, 11 proved positive. The two negative extracts were samples collected one month after the onset of clinical symptoms and signs. The samples richest in particles were those collected during the preicteric phase of the disease. In those cases in which samples were collected during jaundice, the viral concentration was lower. The limit of detection was a period of five days after the onset of jaundice. Thus, examination for hepatitis A virus in the faeces by electron microscopy may be used to obtain an aetiological diagnosis at the beginning of the disease. In one of the patients, a study of the kinetics of the appearance of antibodies was possible. From the time of onset of jaundice, the presence of specific antibodies was noted, reaching a maximum after two months. In the children's institution, no cases of hepatitis A were seen among those entrants who had received an injection of standard polyvalent gammaglobulin at the time of admission.", "contents": "[The identification of hepatitis A virus in faeces. Diagnosis and epidemiological value (author's transl)]. During 1976, two hepatitis A epidemics in institutions enabled the authors to study the presence of the virus in the faeces during the course of the disease. After concentration of feacal extracts in polyethyleneglycol 6000, virions were observed by immune electron microscopy. Among 13 stool extracts examined, 11 proved positive. The two negative extracts were samples collected one month after the onset of clinical symptoms and signs. The samples richest in particles were those collected during the preicteric phase of the disease. In those cases in which samples were collected during jaundice, the viral concentration was lower. The limit of detection was a period of five days after the onset of jaundice. Thus, examination for hepatitis A virus in the faeces by electron microscopy may be used to obtain an aetiological diagnosis at the beginning of the disease. In one of the patients, a study of the kinetics of the appearance of antibodies was possible. From the time of onset of jaundice, the presence of specific antibodies was noted, reaching a maximum after two months. In the children's institution, no cases of hepatitis A were seen among those entrants who had received an injection of standard polyvalent gammaglobulin at the time of admission."}
{"id": "PMID:202925", "title": "The use of nuclease P1 in sequence analysis of end group labeled RNA.", "content": "A method is described for the direct sequence analysis of 20-25 nucleotides from the termini of 5'- or 3'-end-group [32P] labeled RNA. The method involves partial endonucleolytic digestion of the labeled RNA with nuclease P1 (from Penicillium citrinum) followed by separation of the partial digestion products by two-dimensional homochromatography, the nucleotide sequence being determined by mobility shift analysis. This procedure has been applied to the sequence analysis of the terminal regions of tRNAs and of high molecular weight RNA, such as messenger RNA or viral RNA. A further application involves its use in conjunction with snake venom phosphodiesterase to determine the sequence of 5'-end group labeled oligonucleotides, containing modified bases, derived from T1 or pancreatic RNase digestion of tRNA.", "contents": "The use of nuclease P1 in sequence analysis of end group labeled RNA. A method is described for the direct sequence analysis of 20-25 nucleotides from the termini of 5'- or 3'-end-group [32P] labeled RNA. The method involves partial endonucleolytic digestion of the labeled RNA with nuclease P1 (from Penicillium citrinum) followed by separation of the partial digestion products by two-dimensional homochromatography, the nucleotide sequence being determined by mobility shift analysis. This procedure has been applied to the sequence analysis of the terminal regions of tRNAs and of high molecular weight RNA, such as messenger RNA or viral RNA. A further application involves its use in conjunction with snake venom phosphodiesterase to determine the sequence of 5'-end group labeled oligonucleotides, containing modified bases, derived from T1 or pancreatic RNase digestion of tRNA."}
{"id": "PMID:202926", "title": "End labeling of enzymatically decapped mRNA.", "content": "A method is presented for rapid and efficient 5' end labeling with 32P of capped mRNAs, by a series of three enzymatic reactions: the blocking nucleotide of the cap structure is removed by tobacco acid pyrophosphatase, and after dephosphorylation with alkaline phosphatase the 5' end is labeled with gamma-32-P-ATP and T4 polynucleotide kinase.", "contents": "End labeling of enzymatically decapped mRNA. A method is presented for rapid and efficient 5' end labeling with 32P of capped mRNAs, by a series of three enzymatic reactions: the blocking nucleotide of the cap structure is removed by tobacco acid pyrophosphatase, and after dephosphorylation with alkaline phosphatase the 5' end is labeled with gamma-32-P-ATP and T4 polynucleotide kinase."}
{"id": "PMID:202927", "title": "DNA-relaxing enzyme from Micrococcus luteus.", "content": "A DNA-relaxing enzyme which catalyzes the conversion of superhelical DNA to a non-superhelical covalently closed form has been purified from Micrococcus luteus to near homogeneity by two chromatographic steps. The enzyme is a single polypeptide chain. As determined by sodium dodecyl sulfate - polyacrylamide gel electrophoresis and gel filtration on Sephadex G 150, the molecular weight is 115,000. The DNA-relaxing activity determined as a function of enzyme concentration follows a sigmoidal curve. The enzyme requires Mg++ for activity. In the presence of 4.5 mM Mg++ addition of 50-250 mM KCl yields incompletely relaxed DNA molecules (intermediates); intermediates are also observed in the absence of KCl, when the reaction is carried out at 0 degree C or at Mg++ concentrations exceeding 10 mM.", "contents": "DNA-relaxing enzyme from Micrococcus luteus. A DNA-relaxing enzyme which catalyzes the conversion of superhelical DNA to a non-superhelical covalently closed form has been purified from Micrococcus luteus to near homogeneity by two chromatographic steps. The enzyme is a single polypeptide chain. As determined by sodium dodecyl sulfate - polyacrylamide gel electrophoresis and gel filtration on Sephadex G 150, the molecular weight is 115,000. The DNA-relaxing activity determined as a function of enzyme concentration follows a sigmoidal curve. The enzyme requires Mg++ for activity. In the presence of 4.5 mM Mg++ addition of 50-250 mM KCl yields incompletely relaxed DNA molecules (intermediates); intermediates are also observed in the absence of KCl, when the reaction is carried out at 0 degree C or at Mg++ concentrations exceeding 10 mM."}
{"id": "PMID:202928", "title": "The sv40 transcription complex. I. Effect of viral chromatin proteins on endogenous RNA polymerase activity.", "content": "SV40 chromatin obtained from infected monkey cells was used to study the effect of the viral chromatin proteins on endogenous RNA polymerase II. Ammonium sulfate activated the rate of transcription by endogenous RNA polymerase in two ways: 1) by direct action on the enzyme; and 2) by causing a reversible conformational change in the viral chromatin. Under optimal reaction conditions, the viral chromatin proteins did not limit the rate of RNA chain elongation, and high molecular weight RNA (1.6 X 10(6) d) was synthesized by the SV40 chromatin.", "contents": "The sv40 transcription complex. I. Effect of viral chromatin proteins on endogenous RNA polymerase activity. SV40 chromatin obtained from infected monkey cells was used to study the effect of the viral chromatin proteins on endogenous RNA polymerase II. Ammonium sulfate activated the rate of transcription by endogenous RNA polymerase in two ways: 1) by direct action on the enzyme; and 2) by causing a reversible conformational change in the viral chromatin. Under optimal reaction conditions, the viral chromatin proteins did not limit the rate of RNA chain elongation, and high molecular weight RNA (1.6 X 10(6) d) was synthesized by the SV40 chromatin."}
{"id": "PMID:202929", "title": "The sv40 transcription complex. II. Non-dissociation of protein from SV40 chromatin during transcription.", "content": "A small fraction of the SV40 chromatin isolated from infected monkey cell cultures by the Triton method contains active RNA polymerase which had initiated transcription in vivo. This viral transcription complex (VTC) was utilized to answer the question of whether proteins dissociate from chromatin during transcription in vitro. 3H-RNA was synthesized by the VTC under conditions such that over half the label was in transcripts which were longer than half the length of the SV40 genome. Virtually all of the 3H-RNA remained associated with the SV40 chromatin, causing an increase in sedimentation rate from 55S to 78S. The density of the VTC-3H-RNA complex indicated that less than 5% of the original protein dissociated from the SV40 DNA which served as a template for transcription. We conclude that SV40 chromatin can be transcribed while the proteins remain associated with the DNA.", "contents": "The sv40 transcription complex. II. Non-dissociation of protein from SV40 chromatin during transcription. A small fraction of the SV40 chromatin isolated from infected monkey cell cultures by the Triton method contains active RNA polymerase which had initiated transcription in vivo. This viral transcription complex (VTC) was utilized to answer the question of whether proteins dissociate from chromatin during transcription in vitro. 3H-RNA was synthesized by the VTC under conditions such that over half the label was in transcripts which were longer than half the length of the SV40 genome. Virtually all of the 3H-RNA remained associated with the SV40 chromatin, causing an increase in sedimentation rate from 55S to 78S. The density of the VTC-3H-RNA complex indicated that less than 5% of the original protein dissociated from the SV40 DNA which served as a template for transcription. We conclude that SV40 chromatin can be transcribed while the proteins remain associated with the DNA."}
{"id": "PMID:202939", "title": "[Some aspects of protein methylation].", "content": "The paper gives a review of the literature publications on protein methylation and probable donors of methyl groups. It presents experimental data demonstrating the capability of 14CH3-B12 to methylate in vitro proteins of tRNA methylases from Zajdela ascite hepatoma and rat liver as well as commercial RNase and albumin preparations.", "contents": "[Some aspects of protein methylation]. The paper gives a review of the literature publications on protein methylation and probable donors of methyl groups. It presents experimental data demonstrating the capability of 14CH3-B12 to methylate in vitro proteins of tRNA methylases from Zajdela ascite hepatoma and rat liver as well as commercial RNase and albumin preparations."}
{"id": "PMID:202940", "title": "[Biological method of quantitating vitamin D in different preparations and diets].", "content": "A biological method for quantitative assay of vitamin D3 in various preparations has been developed. The method is based on a close correlation between the vitamin D3 dose and the content of calcium-binding protein in the duodenal mucosa of rachitic chickens 72 hrs after vitamin D3 administration. Calcium-binding protein is assayed by radial immunodiffusion in agar-agar. The calibration curve of the dose-protein dependence allows measurements of I to 500 IU of vitamin D3 in the sample tested. The method shows good accuracy and reproducibility. The paper presents the results of quantitation of vitamin D in various preparations.", "contents": "[Biological method of quantitating vitamin D in different preparations and diets]. A biological method for quantitative assay of vitamin D3 in various preparations has been developed. The method is based on a close correlation between the vitamin D3 dose and the content of calcium-binding protein in the duodenal mucosa of rachitic chickens 72 hrs after vitamin D3 administration. Calcium-binding protein is assayed by radial immunodiffusion in agar-agar. The calibration curve of the dose-protein dependence allows measurements of I to 500 IU of vitamin D3 in the sample tested. The method shows good accuracy and reproducibility. The paper presents the results of quantitation of vitamin D in various preparations."}
{"id": "PMID:202942", "title": "[Effect of ACTH on protein phosphorylation in rat adrenal ribosomes].", "content": "The authors studied the influence of ACTH on the steroidogenesis and 32P-labeled KH2PO4 incorporation into the ribosome proteins under conditions of incubation of the rat adrenal glands in vitro. 30 minutes before the incubation ACTH added into the medium stimulated corticosteroid biosynthesis by 116 +/- 26% and increased the radioactive phosphorus incorporation into the sum total ribosome proteins by 38 +/- 7%. Ribosome proteins were separated by electrophoresis in polyacrylamide gel at pH 4.5 into 30 fractions. 5--6 protein fractions proved to be phosphorylated during the incubation. ACTH altered the phosphorylation of individual protein fractions differently: there was stimulation in 2 fractions and inhibition of phosphorylation--in 3. It was revealed that, along with steroidogenesis, ACTH altered the phosphorylation of ribosome proteins. The change of the rate of ribosome phosphorylation was possibly one of the mechanisms with the aid of which the steroidogenic action of ACTH is realized.", "contents": "[Effect of ACTH on protein phosphorylation in rat adrenal ribosomes]. The authors studied the influence of ACTH on the steroidogenesis and 32P-labeled KH2PO4 incorporation into the ribosome proteins under conditions of incubation of the rat adrenal glands in vitro. 30 minutes before the incubation ACTH added into the medium stimulated corticosteroid biosynthesis by 116 +/- 26% and increased the radioactive phosphorus incorporation into the sum total ribosome proteins by 38 +/- 7%. Ribosome proteins were separated by electrophoresis in polyacrylamide gel at pH 4.5 into 30 fractions. 5--6 protein fractions proved to be phosphorylated during the incubation. ACTH altered the phosphorylation of individual protein fractions differently: there was stimulation in 2 fractions and inhibition of phosphorylation--in 3. It was revealed that, along with steroidogenesis, ACTH altered the phosphorylation of ribosome proteins. The change of the rate of ribosome phosphorylation was possibly one of the mechanisms with the aid of which the steroidogenic action of ACTH is realized."}
{"id": "PMID:202946", "title": "Nephrogenous adenosine 3'5' monophosphate as an index of parathyroid function in chronic renal disease.", "content": "The purpose of the study was the evaluation of nephrogenous adenosine 3'5' monophosphate (ncAMP) determinations in the diagnosis of hyperparathyroidism (HPT) in chronic renal disease (CRD). The ratio of cAMP clearance to creatinine clearance (CcAMP/Ccr) was applied as the index of the participation of ncAMP in 24 hr urinary cAMP excretion. In seventy CRD patients, the mean CcAMP/Ccr value was higher than in healthy individuals. A good correlation between plasma iPTH and CcAMP/Ccr ratio was noted. In patients with a ratio higher than 2.5, the signs of HPT were found. The determination of CcAMP/Ccr ratio in CRD may be of value in the assessment of parathyroid hyperactivity.", "contents": "Nephrogenous adenosine 3'5' monophosphate as an index of parathyroid function in chronic renal disease. The purpose of the study was the evaluation of nephrogenous adenosine 3'5' monophosphate (ncAMP) determinations in the diagnosis of hyperparathyroidism (HPT) in chronic renal disease (CRD). The ratio of cAMP clearance to creatinine clearance (CcAMP/Ccr) was applied as the index of the participation of ncAMP in 24 hr urinary cAMP excretion. In seventy CRD patients, the mean CcAMP/Ccr value was higher than in healthy individuals. A good correlation between plasma iPTH and CcAMP/Ccr ratio was noted. In patients with a ratio higher than 2.5, the signs of HPT were found. The determination of CcAMP/Ccr ratio in CRD may be of value in the assessment of parathyroid hyperactivity."}
{"id": "PMID:202947", "title": "Structure of cytochrome c555 of Chlorobium thiosulfatophilum: primitive low-potential cytochrome c.", "content": "Cytochrome c555 is an 86-residue type c cytochrome derived from Chlorobium thiosulfatophilum, an obligately anaerobic green sulfur bacterium which is among the most primitive of living organisms. Here is presented a preliminary structural description of the cytochrome c555 molecule based on its crystallographic structure determination at 2.7-A resolution by multiple isomorphous replacement methods. This structure is of interest not only because of its evolutionary significance but also because the cytochrome c555 molecule possesses an unusually low physiologic oxidoreduction potential (Em,7 = +145 mV) compared with related members of the cytochrome c family. Consequently, determination of its structure may permit a direct assessment of the structural factors responsible for prosthetic group redox potential regulation in type c cytochromes.", "contents": "Structure of cytochrome c555 of Chlorobium thiosulfatophilum: primitive low-potential cytochrome c. Cytochrome c555 is an 86-residue type c cytochrome derived from Chlorobium thiosulfatophilum, an obligately anaerobic green sulfur bacterium which is among the most primitive of living organisms. Here is presented a preliminary structural description of the cytochrome c555 molecule based on its crystallographic structure determination at 2.7-A resolution by multiple isomorphous replacement methods. This structure is of interest not only because of its evolutionary significance but also because the cytochrome c555 molecule possesses an unusually low physiologic oxidoreduction potential (Em,7 = +145 mV) compared with related members of the cytochrome c family. Consequently, determination of its structure may permit a direct assessment of the structural factors responsible for prosthetic group redox potential regulation in type c cytochromes."}
{"id": "PMID:202948", "title": "Characterization of a common precursor to corticotropin and beta-lipotropin: identification of beta-lipotropin peptides and their arrangement relative to corticotropin in the precursor synthesized in a cell-free system.", "content": "Radioactive proteins synthesized in an mRNA-dependent reticulocyte cell-free system under the direction of mRNA from AtT-20/D-16v mouse cells were isolated by specific immunoprecipitation using antiserum to either alpha(1-24) corticotropin or beta-endorphin [beta(61-91) lipotropin]. Each immunoprecipitate was fractionated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and shown to contain only one labeled protein with an apparent molecular weight of 28,500. Tryptic peptide analysis of the Mr 28,500 corticotropin and beta-lipotropin molecules isolated from the gels demonstrated that the two proteins had the same lysine, methionine, and tryptophan peptides. Four tryptic peptides from the cell-free product exhibited the same electrophoretic and chromatographic mobilities as marker tryptic peptides from bovine beta-melanotropin and porcine beta-endorphin. The identification of these peptides was confirmed by amino acid composition studies with a variety of labeled amino acids. The beta-lipotropin tryptic peptides were also shown to be located carboxy terminal to the corticotropin tryptic peptides.", "contents": "Characterization of a common precursor to corticotropin and beta-lipotropin: identification of beta-lipotropin peptides and their arrangement relative to corticotropin in the precursor synthesized in a cell-free system. Radioactive proteins synthesized in an mRNA-dependent reticulocyte cell-free system under the direction of mRNA from AtT-20/D-16v mouse cells were isolated by specific immunoprecipitation using antiserum to either alpha(1-24) corticotropin or beta-endorphin [beta(61-91) lipotropin]. Each immunoprecipitate was fractionated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and shown to contain only one labeled protein with an apparent molecular weight of 28,500. Tryptic peptide analysis of the Mr 28,500 corticotropin and beta-lipotropin molecules isolated from the gels demonstrated that the two proteins had the same lysine, methionine, and tryptophan peptides. Four tryptic peptides from the cell-free product exhibited the same electrophoretic and chromatographic mobilities as marker tryptic peptides from bovine beta-melanotropin and porcine beta-endorphin. The identification of these peptides was confirmed by amino acid composition studies with a variety of labeled amino acids. The beta-lipotropin tryptic peptides were also shown to be located carboxy terminal to the corticotropin tryptic peptides."}
{"id": "PMID:202949", "title": "2'-Deoxy-2'-azidocytidine inhibits the initiation of polyoma DNA synthesis.", "content": "2'-Deoxy-2'-azidocytidine, a nucleoside analogue, inhibits polyoma DNA synthesis. The inhibition results in a 5.5-fold decrease in the amount of replicating intermediates, as detected by electron microscopy. The results indicate that replication is inhibited at an early step, possibly in the initiation of new rounds of replication. In contrast, the effect on the elongation of DNA chains appears to be less pronounced. As a result of the inhibition, polyoma DNA molecules at an early stage of replication accumulate in the nuclei. Upon incubation of such nuclei, DNA synthesis is induced in these molecules. The replication starts from the normal origin and elongation proceeds bidirectionally at a rate close to that observed during in vivo conditions. Analysis of polyoma DNA replication in nuclei isolated from control cells indicates that both initiation and termination of replication are impaired under in vitro conditions.", "contents": "2'-Deoxy-2'-azidocytidine inhibits the initiation of polyoma DNA synthesis. 2'-Deoxy-2'-azidocytidine, a nucleoside analogue, inhibits polyoma DNA synthesis. The inhibition results in a 5.5-fold decrease in the amount of replicating intermediates, as detected by electron microscopy. The results indicate that replication is inhibited at an early step, possibly in the initiation of new rounds of replication. In contrast, the effect on the elongation of DNA chains appears to be less pronounced. As a result of the inhibition, polyoma DNA molecules at an early stage of replication accumulate in the nuclei. Upon incubation of such nuclei, DNA synthesis is induced in these molecules. The replication starts from the normal origin and elongation proceeds bidirectionally at a rate close to that observed during in vivo conditions. Analysis of polyoma DNA replication in nuclei isolated from control cells indicates that both initiation and termination of replication are impaired under in vitro conditions."}
{"id": "PMID:202950", "title": "5'-Terminal sequences and coding region of late simian virus 40 mRNAs are derived from noncontiguous segments of the viral genome.", "content": "The region of the simian virus 40 genome complementary to the 5' end of the most abundant poly(A)-containing 19S and 16S mRNAs was mapped by hybridization of double-labeled RNA ([3H]methyl group and [14C]uridine) to specific DNA fragments. Chemical identification of methylated residues indicated that a common \"leader\" sequence adjacent to the 5' terminus of both 19S and 16S mRNA is transcribed from DNA sequences located between 0.67 and 0.76 map units. The estimated size of this \"leader\" RNA, which does not code for any known viral protein, is 170-200 nucleotides. Our results indicate that sequences complementary to the \"leader\" region and coding portion of 16S mRNA are located in separate parts of the simian virus 40 genome.", "contents": "5'-Terminal sequences and coding region of late simian virus 40 mRNAs are derived from noncontiguous segments of the viral genome. The region of the simian virus 40 genome complementary to the 5' end of the most abundant poly(A)-containing 19S and 16S mRNAs was mapped by hybridization of double-labeled RNA ([3H]methyl group and [14C]uridine) to specific DNA fragments. Chemical identification of methylated residues indicated that a common \"leader\" sequence adjacent to the 5' terminus of both 19S and 16S mRNA is transcribed from DNA sequences located between 0.67 and 0.76 map units. The estimated size of this \"leader\" RNA, which does not code for any known viral protein, is 170-200 nucleotides. Our results indicate that sequences complementary to the \"leader\" region and coding portion of 16S mRNA are located in separate parts of the simian virus 40 genome."}
{"id": "PMID:202951", "title": "Renaturation of complementary single-stranded DNA circles: complete rewinding facilitated by the DNA untwisting enzyme.", "content": "Renaturation of two complementary single-stranded circles should be limited by topological constraints against the rewinding of the DNA helix. If a mixture of complementary single-stranded rings is annealed and then treated with the DNA untwisting enzyme, the DNA circles completely renature as judged by (i) the presence of interlocked rings that sediment at 53 S in alkali, (ii) the buoyant density of the renatured DNA in CsCl gradients containing ethidium bromide, and (iii) the resistance of the product to the single-strand-specific S1 nuclease. Therefore, the DNA untwisting enzyme is able to provide a transient single-strand break that is sufficient to allow the two strands to completely rewind. The possibility that the untwisting enzyme might facilitate the initiation of the process of genetic recombination is discussed.", "contents": "Renaturation of complementary single-stranded DNA circles: complete rewinding facilitated by the DNA untwisting enzyme. Renaturation of two complementary single-stranded circles should be limited by topological constraints against the rewinding of the DNA helix. If a mixture of complementary single-stranded rings is annealed and then treated with the DNA untwisting enzyme, the DNA circles completely renature as judged by (i) the presence of interlocked rings that sediment at 53 S in alkali, (ii) the buoyant density of the renatured DNA in CsCl gradients containing ethidium bromide, and (iii) the resistance of the product to the single-strand-specific S1 nuclease. Therefore, the DNA untwisting enzyme is able to provide a transient single-strand break that is sufficient to allow the two strands to completely rewind. The possibility that the untwisting enzyme might facilitate the initiation of the process of genetic recombination is discussed."}
{"id": "PMID:202952", "title": "The 5'-terminal structures of poliovirion RNA and poliovirus mRNA differ only in the genome-linked protein VPg.", "content": "The 5'-terminal, RNase T1-resistant oligonucleotide of poliovirus mRNA has been isolated. Its sequence is pU-U-A-A-A-A-C-A-Gp, which is identical to that of virion RNA except that the genome-linked protein VPg is absent [Nomoto, A., Detjen, B., Pozzatti, R. & Wimmer, E. (1977) Nature 268, 208-213]. Because all newly synthesized viral RNAs are VPg-linked, we propose that VPg is cleaved from progeny RNA at the linkage between protein and nucleic acid prior to polyribosome formation. This may represent a new mode of processing of viral macromolecules. Virion RNA from which VPg has been cleaved proteolytically retains its specific infectivity, an observation suggesting that VPg is not involved in early steps (penetration and translation) of the infectious cycle initiated by RNA.", "contents": "The 5'-terminal structures of poliovirion RNA and poliovirus mRNA differ only in the genome-linked protein VPg. The 5'-terminal, RNase T1-resistant oligonucleotide of poliovirus mRNA has been isolated. Its sequence is pU-U-A-A-A-A-C-A-Gp, which is identical to that of virion RNA except that the genome-linked protein VPg is absent [Nomoto, A., Detjen, B., Pozzatti, R. & Wimmer, E. (1977) Nature 268, 208-213]. Because all newly synthesized viral RNAs are VPg-linked, we propose that VPg is cleaved from progeny RNA at the linkage between protein and nucleic acid prior to polyribosome formation. This may represent a new mode of processing of viral macromolecules. Virion RNA from which VPg has been cleaved proteolytically retains its specific infectivity, an observation suggesting that VPg is not involved in early steps (penetration and translation) of the infectious cycle initiated by RNA."}
{"id": "PMID:202953", "title": "Asymmetric binding of the inhibitor di(adenosine-5') pentaphosphate (Ap5A) to adenylate kinase.", "content": "The effect of binding diadenosine pentaphosphate (Ap(5)A) to adenylate kinase (ATP:AMP phosphotransferase; EC 2.7.4.3) has been investigated by (31)P nuclear magnetic resonance. The symmetric molecule, Ap(5)A, is a potent inhibitor of the adenylate kinase reaction, 2 ADP right arrow over left arrow ATP + AMP. Free Ap(5)A has two groups of signals in its (31)P nuclear magnetic resonance spectrum centered at 11.1 and 22.8 parts/million (ppm) upfield from 85% H(3)PO(4) that are assigned to the end (1-P and 5-P) and middle (2-, 3-, and 4-P) phosphates, respectively. Addition of Mg(2+) shifts the centers of these resonances to 11.7 and 22.3 ppm. The spectrum of Ap(5)A bound to porcine adenylate kinase shows five groups of signals centered at 10.9, 11.9, 20.5, 22.7, and 24.0 ppm; the resonances at 11.1 ppm (1-P and 5-P) and at 22.8 ppm (2-P and 4-P) are now clearly split, indicating asymmetric binding of Ap(5)A to the enzyme. The asymmetry is strikingly enhanced in enzyme-bound MgAp(5)A, which has resonances at 10.5, 12.5, 18.6, 22.7, and 25.6 ppm. By the addition of Mn(2+) to the enzyme.MgAp(5)A complex, the observed signals in increasing order of shifts were tentatively assigned to 1-P, 5-P, 4-P, 3-P, and 2-P, where the 3-, 4-, and 5-P positions correspond to the ATP-binding site on the enzyme. The asymmetry introduced in the phosphate chain of enzyme.MgAp(5)A is indicated by the (31)P chemical shift of 7 ppm between 2- and 4-P, which is one of the largest thus far observed for phosphate substrates bound noncovalently to enzymes.", "contents": "Asymmetric binding of the inhibitor di(adenosine-5') pentaphosphate (Ap5A) to adenylate kinase. The effect of binding diadenosine pentaphosphate (Ap(5)A) to adenylate kinase (ATP:AMP phosphotransferase; EC 2.7.4.3) has been investigated by (31)P nuclear magnetic resonance. The symmetric molecule, Ap(5)A, is a potent inhibitor of the adenylate kinase reaction, 2 ADP right arrow over left arrow ATP + AMP. Free Ap(5)A has two groups of signals in its (31)P nuclear magnetic resonance spectrum centered at 11.1 and 22.8 parts/million (ppm) upfield from 85% H(3)PO(4) that are assigned to the end (1-P and 5-P) and middle (2-, 3-, and 4-P) phosphates, respectively. Addition of Mg(2+) shifts the centers of these resonances to 11.7 and 22.3 ppm. The spectrum of Ap(5)A bound to porcine adenylate kinase shows five groups of signals centered at 10.9, 11.9, 20.5, 22.7, and 24.0 ppm; the resonances at 11.1 ppm (1-P and 5-P) and at 22.8 ppm (2-P and 4-P) are now clearly split, indicating asymmetric binding of Ap(5)A to the enzyme. The asymmetry is strikingly enhanced in enzyme-bound MgAp(5)A, which has resonances at 10.5, 12.5, 18.6, 22.7, and 25.6 ppm. By the addition of Mn(2+) to the enzyme.MgAp(5)A complex, the observed signals in increasing order of shifts were tentatively assigned to 1-P, 5-P, 4-P, 3-P, and 2-P, where the 3-, 4-, and 5-P positions correspond to the ATP-binding site on the enzyme. The asymmetry introduced in the phosphate chain of enzyme.MgAp(5)A is indicated by the (31)P chemical shift of 7 ppm between 2- and 4-P, which is one of the largest thus far observed for phosphate substrates bound noncovalently to enzymes."}
{"id": "PMID:202954", "title": "Guanosinetriphosphatase activity of tubulin associated with microtubule assembly.", "content": "Tubulin, purified by cycles of assembly followed by phosphocellulose chromatography, exhibits a characteristic GTPase activity that is polymerization dependent and can be attributed to the tubulin itself. This activity has been observed, in a standard reassembly buffer containing low Mg2+, under three conditions that induce microtubule assembly: in the presence of microtubule-associated proteins, in the presence of DEAE-dextran, or after addition of high Mg2+ and glycerol. The phosphocellulose-purified tubulin showed no GTPase activity under the following nonpolymerizing conditions: in buffer with low Mg2+ in the absence of microtubule-associated proteins or DEAE-dextran, in buffer with high Mg2+ and glycerol at tubulin concentrations below the critical concentration, or when microtubule assembly was inhibited by vinblastine. Colchicine, on the other hand, while blocking microtubule assembly, induced a significant GTPase activity in the phosphocellulose-purified tubulin. During the process of assembly, GTP appears to be hydrolyzed as a free tubulin dimer polymerizes into a microtubule. A constant GTPase activity when polymerization equilibrium is reached apparently reflects the cyclic polymerization-depolymerization of tubulin dimers at the ends of the microtubules.", "contents": "Guanosinetriphosphatase activity of tubulin associated with microtubule assembly. Tubulin, purified by cycles of assembly followed by phosphocellulose chromatography, exhibits a characteristic GTPase activity that is polymerization dependent and can be attributed to the tubulin itself. This activity has been observed, in a standard reassembly buffer containing low Mg2+, under three conditions that induce microtubule assembly: in the presence of microtubule-associated proteins, in the presence of DEAE-dextran, or after addition of high Mg2+ and glycerol. The phosphocellulose-purified tubulin showed no GTPase activity under the following nonpolymerizing conditions: in buffer with low Mg2+ in the absence of microtubule-associated proteins or DEAE-dextran, in buffer with high Mg2+ and glycerol at tubulin concentrations below the critical concentration, or when microtubule assembly was inhibited by vinblastine. Colchicine, on the other hand, while blocking microtubule assembly, induced a significant GTPase activity in the phosphocellulose-purified tubulin. During the process of assembly, GTP appears to be hydrolyzed as a free tubulin dimer polymerizes into a microtubule. A constant GTPase activity when polymerization equilibrium is reached apparently reflects the cyclic polymerization-depolymerization of tubulin dimers at the ends of the microtubules."}
{"id": "PMID:202955", "title": "Deuterium magnetic resonance studies of the interaction of lipids with membrane proteins.", "content": "The deuterium magnetic resonance spectra of lipid-protein particles containing cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) isolated from beef heart mitochondria and the specifically deuterated lipid 1-(16,16,16-trideuteropalmitoyl)-2-palmitoleoyl phosphatidylcholine are presented. These reconstituted particles are of uniform lipid and protein content; however, the spectra clearly show two environments characterized by distinctly different residual quadrupolar splittings or order parameters. The less-ordered environment shows a splitting similar to but slightly less than that of the pure lipid alone at a given temperature. The more restricted environment appears to be induced by the presence of the protein. The amount of the restricted lipid is clearly temperature dependent with a 2- to 3-fold decrease in relative amount from 2 to 22 degrees. The rate of exchange of lipid between the free and restricted environments is slower than 10(3)/sec. The significance of these phenomena is discussed.", "contents": "Deuterium magnetic resonance studies of the interaction of lipids with membrane proteins. The deuterium magnetic resonance spectra of lipid-protein particles containing cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) isolated from beef heart mitochondria and the specifically deuterated lipid 1-(16,16,16-trideuteropalmitoyl)-2-palmitoleoyl phosphatidylcholine are presented. These reconstituted particles are of uniform lipid and protein content; however, the spectra clearly show two environments characterized by distinctly different residual quadrupolar splittings or order parameters. The less-ordered environment shows a splitting similar to but slightly less than that of the pure lipid alone at a given temperature. The more restricted environment appears to be induced by the presence of the protein. The amount of the restricted lipid is clearly temperature dependent with a 2- to 3-fold decrease in relative amount from 2 to 22 degrees. The rate of exchange of lipid between the free and restricted environments is slower than 10(3)/sec. The significance of these phenomena is discussed."}
{"id": "PMID:202956", "title": "Transfer of ADP-ribose from NAD to choleragen: a subunit acts as catalyst and acceptor protein.", "content": "Choleragen selectively incorporates 3H from [3H]NAD labeled on the adenosine moiety and not 14C from [14C]NAD labeled on the nicotinamide moiety. This reaction does not require protein in addition to choleragen. Incorporation of isotope does not proceed at 4 degrees, requires dithiothreitol, is stable after extensive washing with cold trichloroacetic acid, and is decreased 80% by boiling in trichloroacetic acid. Studies with the A and B subunits of choleragen show that the A subunit catalyzes ADP-ribosylation and serves as an acceptor protein. The B subunit does not show catalytic or acceptor activity. We conclude that choleragen and its A subunit catalyze the hydrolysis of NAD and the enzymatic transfer of ADP-ribose to the A subunit.", "contents": "Transfer of ADP-ribose from NAD to choleragen: a subunit acts as catalyst and acceptor protein. Choleragen selectively incorporates 3H from [3H]NAD labeled on the adenosine moiety and not 14C from [14C]NAD labeled on the nicotinamide moiety. This reaction does not require protein in addition to choleragen. Incorporation of isotope does not proceed at 4 degrees, requires dithiothreitol, is stable after extensive washing with cold trichloroacetic acid, and is decreased 80% by boiling in trichloroacetic acid. Studies with the A and B subunits of choleragen show that the A subunit catalyzes ADP-ribosylation and serves as an acceptor protein. The B subunit does not show catalytic or acceptor activity. We conclude that choleragen and its A subunit catalyze the hydrolysis of NAD and the enzymatic transfer of ADP-ribose to the A subunit."}
{"id": "PMID:202957", "title": "Characterization of early simian virus 40 transcriptional complexes: late transcription in the absence of detectable DNA replication.", "content": "Isolation of early viral transcriptional complexes and incorporation in vitro of radiolabeled precursors into nascent RNA has permitted an analysis of early simian virus 40 (SV40) transcription. Under conditions such that viral DNA replication was undetectable, both early and late SV40 RNA were synthesized. This finding provides evidence that viral DNA replication is not an absolute requirement for late transcription and supports earlier observations that late viral RNA is synthesized in SV40-infected nonpermissive mouse cells. The majority of the early viral transcriptional activity can be solubilized, indicating that a substantial portion of this RNA is transcribed from free rather than integrated templates. Sedimentation analysis of the transcriptional complexes resulted in the detection of two separate peaks of activity, suggesting the possibility of two distinct types of early SV40 templates.", "contents": "Characterization of early simian virus 40 transcriptional complexes: late transcription in the absence of detectable DNA replication. Isolation of early viral transcriptional complexes and incorporation in vitro of radiolabeled precursors into nascent RNA has permitted an analysis of early simian virus 40 (SV40) transcription. Under conditions such that viral DNA replication was undetectable, both early and late SV40 RNA were synthesized. This finding provides evidence that viral DNA replication is not an absolute requirement for late transcription and supports earlier observations that late viral RNA is synthesized in SV40-infected nonpermissive mouse cells. The majority of the early viral transcriptional activity can be solubilized, indicating that a substantial portion of this RNA is transcribed from free rather than integrated templates. Sedimentation analysis of the transcriptional complexes resulted in the detection of two separate peaks of activity, suggesting the possibility of two distinct types of early SV40 templates."}
{"id": "PMID:202958", "title": "Stimulation of sugar uptake and thymidine incorporation in mouse 3T3 cells by calcium phosphate and other extracellular particles.", "content": "Evidence is presented that the marked stimulation of sugar uptake and thymidine incorporation by addition of extra Ca2+ to stationary phase mouse 3T3 cells in culture is phosphate dependent and due to the action of the calcium phosphate precipitate formed in the medium. The cells are similarly stimulated by a variety of particulate materials, including calcium pyrophosphate, barium sulfate, kaolin, and polystrene beads. The precipitate effects on sugar uptake are of the same magnitude as those seen with certain hormones (insulin, epidermal growth factor) or with fresh 10% calf serum. The effect of barium sulfate on thymidine incorporation is also of the same magnitude as seen with these hormones, but much less than half that found with fresh calf serum. The stimulation by barium sulfate or hormones of thymidine incorporation is not phosphate dependent.", "contents": "Stimulation of sugar uptake and thymidine incorporation in mouse 3T3 cells by calcium phosphate and other extracellular particles. Evidence is presented that the marked stimulation of sugar uptake and thymidine incorporation by addition of extra Ca2+ to stationary phase mouse 3T3 cells in culture is phosphate dependent and due to the action of the calcium phosphate precipitate formed in the medium. The cells are similarly stimulated by a variety of particulate materials, including calcium pyrophosphate, barium sulfate, kaolin, and polystrene beads. The precipitate effects on sugar uptake are of the same magnitude as those seen with certain hormones (insulin, epidermal growth factor) or with fresh 10% calf serum. The effect of barium sulfate on thymidine incorporation is also of the same magnitude as seen with these hormones, but much less than half that found with fresh calf serum. The stimulation by barium sulfate or hormones of thymidine incorporation is not phosphate dependent."}
{"id": "PMID:202959", "title": "Feline oncornavirus-associated cell membrane antigen: evidence for an immunologically crossreactive feline sarcoma virus-coded protein.", "content": "The feline oncornavirus-associated cell membrane antigen (FOCMA) acts as a target for natural immuno-surveillance against tumor development in the cat. In the present study, mink and rat cells nonproductively transformed by feline sarcoma virus (FeSV) were shown to express FOCMA as well as 5'-terminal feline leukemia virus (FeLV) gag gene proteins, p15 and p12. In contrast, such cells lack detectable levels of other FeLV gag gene-coded proteins or the env gene product, gp70. FOCMA, p15, and p12 antigen expression is initially in the form of an 80,000-100,000 molecular weight precursor which, upon post-translational cleavage, gives rise to a 65,000 molecular weight component that contains FOCMA and a 25,000 molecular weight component containing p15 and p12. Feline lymphoma cells, including those from several tumors that lacked detectable levels of FeLV structural protein expression, were shown to be FOCMA-positive. These findings strongly suggest that FOCMA represents an FeSV-coded transformation specific protein and provide preliminary information regarding the position within the FeSV genome coding for its synthesis.", "contents": "Feline oncornavirus-associated cell membrane antigen: evidence for an immunologically crossreactive feline sarcoma virus-coded protein. The feline oncornavirus-associated cell membrane antigen (FOCMA) acts as a target for natural immuno-surveillance against tumor development in the cat. In the present study, mink and rat cells nonproductively transformed by feline sarcoma virus (FeSV) were shown to express FOCMA as well as 5'-terminal feline leukemia virus (FeLV) gag gene proteins, p15 and p12. In contrast, such cells lack detectable levels of other FeLV gag gene-coded proteins or the env gene product, gp70. FOCMA, p15, and p12 antigen expression is initially in the form of an 80,000-100,000 molecular weight precursor which, upon post-translational cleavage, gives rise to a 65,000 molecular weight component that contains FOCMA and a 25,000 molecular weight component containing p15 and p12. Feline lymphoma cells, including those from several tumors that lacked detectable levels of FeLV structural protein expression, were shown to be FOCMA-positive. These findings strongly suggest that FOCMA represents an FeSV-coded transformation specific protein and provide preliminary information regarding the position within the FeSV genome coding for its synthesis."}
{"id": "PMID:202960", "title": "Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency: possible role of nucleoside kinase(s).", "content": "Inherited deficiencies of the enzymes adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) and purine nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase; EC 2.4.2.1) preferentially interfere with lymphocyte development while sparing most other organ systems. Previous experiments have shown that through the action of specific kinases, nucleosides can be \"trapped\" intracellularly in the form of 5'-phosphates. We therefore measured the ability of newborn human tissues to phosphorylate adenosine and deoxyadenosine, the substrate of adenosine deaminase, and also inosine, deoxyinosine, guanosine, and deoxyguanosine, the substrates of purine nucleoside phosphorylase. Substantial activities of adenosine kinase were found in all tissues studied, while guanosine and inosine kinases were detected in none. However, the ability to phosphorylate deoxyadenosine, deoxyinosine, and deoxyguanosine was largely confined to lymphocytes. Adenosine deaminase, but not purine nucleoside phosphorylase, showed a similar lymphoid predominance. Other experiments showed that deoxyadenosine, deoxyinosine, and deoxyguanosine were toxic to human lymphoid cells. The toxicity of deoxyadenosine was reversed by the addition of deoxycytidine, but not uridine, to the culture medium. Based upon these and other experiments, we propose that in adenosine deaminase and purine nucleoside phosphorylase deficiency, toxic deoxyribonucleosides produced by many tissues are selectively trapped in lymphocytes by phosphorylating enzyme(s).", "contents": "Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency: possible role of nucleoside kinase(s). Inherited deficiencies of the enzymes adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) and purine nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase; EC 2.4.2.1) preferentially interfere with lymphocyte development while sparing most other organ systems. Previous experiments have shown that through the action of specific kinases, nucleosides can be \"trapped\" intracellularly in the form of 5'-phosphates. We therefore measured the ability of newborn human tissues to phosphorylate adenosine and deoxyadenosine, the substrate of adenosine deaminase, and also inosine, deoxyinosine, guanosine, and deoxyguanosine, the substrates of purine nucleoside phosphorylase. Substantial activities of adenosine kinase were found in all tissues studied, while guanosine and inosine kinases were detected in none. However, the ability to phosphorylate deoxyadenosine, deoxyinosine, and deoxyguanosine was largely confined to lymphocytes. Adenosine deaminase, but not purine nucleoside phosphorylase, showed a similar lymphoid predominance. Other experiments showed that deoxyadenosine, deoxyinosine, and deoxyguanosine were toxic to human lymphoid cells. The toxicity of deoxyadenosine was reversed by the addition of deoxycytidine, but not uridine, to the culture medium. Based upon these and other experiments, we propose that in adenosine deaminase and purine nucleoside phosphorylase deficiency, toxic deoxyribonucleosides produced by many tissues are selectively trapped in lymphocytes by phosphorylating enzyme(s)."}
{"id": "PMID:202961", "title": "Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine.", "content": "A guanine derivative with an acyclic side chain, 2-hydroxyethoxymethyl, at position 9 has potent antiviral activity [dose for 50% inhibition (ED(50)) = 0.1 muM] against herpes simplex virus type 1. This acyclic nucleoside analog, termed acycloguanosine, is converted to a monophosphate by a virus-specified pyrimidine deoxynucleoside (thymidine) kinase and is subsequently converted to acycloguanosine di- and triphosphates. In the uninfected host cell (Vero) these phosphorylations of acycloguanosine occur to a very limited extent. Acycloguanosine triphosphate inhibits herpes simplex virus DNA polymerase (DNA nucleotidyltransferase) 10-30 times more effectively than cellular (HeLa S3) DNA polymerase. These factors contribute to the drug's selectivity; inhibition of growth of the host cell requires a 3000-fold greater concentration of drug than does the inhibition of viral multiplication. There is, moreover, the strong possibility of chain termination of the viral DNA by incorporation of acycloguanosine. The identity of the kinase that phosphorylates acycloguanosine was determined after separation of the cellular and virus-specified thymidine kinase activities by affinity chromatography, by reversal studies with thymidine, and by the lack of monophosphate formation in a temperature-sensitive, thymidine kinase-deficient mutant of the KOS strain of herpes simplex virus type 1 (tsA1).", "contents": "Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. A guanine derivative with an acyclic side chain, 2-hydroxyethoxymethyl, at position 9 has potent antiviral activity [dose for 50% inhibition (ED(50)) = 0.1 muM] against herpes simplex virus type 1. This acyclic nucleoside analog, termed acycloguanosine, is converted to a monophosphate by a virus-specified pyrimidine deoxynucleoside (thymidine) kinase and is subsequently converted to acycloguanosine di- and triphosphates. In the uninfected host cell (Vero) these phosphorylations of acycloguanosine occur to a very limited extent. Acycloguanosine triphosphate inhibits herpes simplex virus DNA polymerase (DNA nucleotidyltransferase) 10-30 times more effectively than cellular (HeLa S3) DNA polymerase. These factors contribute to the drug's selectivity; inhibition of growth of the host cell requires a 3000-fold greater concentration of drug than does the inhibition of viral multiplication. There is, moreover, the strong possibility of chain termination of the viral DNA by incorporation of acycloguanosine. The identity of the kinase that phosphorylates acycloguanosine was determined after separation of the cellular and virus-specified thymidine kinase activities by affinity chromatography, by reversal studies with thymidine, and by the lack of monophosphate formation in a temperature-sensitive, thymidine kinase-deficient mutant of the KOS strain of herpes simplex virus type 1 (tsA1)."}
{"id": "PMID:202962", "title": "Interspecies radioimmunoassay for the major structural proteins of primate type-D retroviruses.", "content": "A competition radioimmunoassay has been developed in which type-D retroviruses from three primate species compete. The assay utilizes the major structural protein (36,000 daltons) of the endogenous squirrel monkey retrovirus and antisera directed against the major structural protein (27,000 daltons) of the Mason-Pfizer monkey virus isolated from rhesus monkeys. Purified preparations of both viruses grown in heterologous cells, as well as extracts of heterologous cells infected with squirrel monkey retrovirus or Mason-Pfizer monkey virus, compete completely in the assay. Addition of an endogenous virus of the langur monkey also results in complete blocking. No blocking in the assay is observed with type-C baboon viruses, woolly monkey virus, and gibbon virus. Various other type-C and type-B viruses also showed no reactivity. An interspecies assay has thus been developed that recognizes the type-D retroviruses from both Old World monkey (rhesus and langur) and New World monkey (squirrel) species.", "contents": "Interspecies radioimmunoassay for the major structural proteins of primate type-D retroviruses. A competition radioimmunoassay has been developed in which type-D retroviruses from three primate species compete. The assay utilizes the major structural protein (36,000 daltons) of the endogenous squirrel monkey retrovirus and antisera directed against the major structural protein (27,000 daltons) of the Mason-Pfizer monkey virus isolated from rhesus monkeys. Purified preparations of both viruses grown in heterologous cells, as well as extracts of heterologous cells infected with squirrel monkey retrovirus or Mason-Pfizer monkey virus, compete completely in the assay. Addition of an endogenous virus of the langur monkey also results in complete blocking. No blocking in the assay is observed with type-C baboon viruses, woolly monkey virus, and gibbon virus. Various other type-C and type-B viruses also showed no reactivity. An interspecies assay has thus been developed that recognizes the type-D retroviruses from both Old World monkey (rhesus and langur) and New World monkey (squirrel) species."}
{"id": "PMID:202963", "title": "Opiate receptor: cooperativity of binding observed in brain slices.", "content": "Kinetic constants for binding of 3H-labeled morphine and naloxone were determined from Hill plot analyses and from experiments in which the concentration of tritiated drug was constant and that of nonlabeled drug varied. With brain slices, the binding of either drug exhibited strong positive cooperativity (Hill slope greater than 3); this was not observed in brain homogenates. Thus, in slices the relationship between opiate binding site and ligand may be more relevant physiologically and pharmacologically.", "contents": "Opiate receptor: cooperativity of binding observed in brain slices. Kinetic constants for binding of 3H-labeled morphine and naloxone were determined from Hill plot analyses and from experiments in which the concentration of tritiated drug was constant and that of nonlabeled drug varied. With brain slices, the binding of either drug exhibited strong positive cooperativity (Hill slope greater than 3); this was not observed in brain homogenates. Thus, in slices the relationship between opiate binding site and ligand may be more relevant physiologically and pharmacologically."}
{"id": "PMID:202979", "title": "EPR study of serum ceruloplasmin and iron transferrin in myocardial infarction.", "content": "Electron paramagnetic resonance (EPR) analysis of frozen serum from myocardial infarction patients has been conducted. Signal at g=4.3 was found definitively attributable to iron(III)-transferrin complex. Imcrease of serum ceruloplasmin as compared to normal was confirmed, with a concomitant decrease of iron-transferrin content. A mechanism for such correlated variation is hypothesized.", "contents": "EPR study of serum ceruloplasmin and iron transferrin in myocardial infarction. Electron paramagnetic resonance (EPR) analysis of frozen serum from myocardial infarction patients has been conducted. Signal at g=4.3 was found definitively attributable to iron(III)-transferrin complex. Imcrease of serum ceruloplasmin as compared to normal was confirmed, with a concomitant decrease of iron-transferrin content. A mechanism for such correlated variation is hypothesized."}
{"id": "PMID:202980", "title": "Submandibular gland tumors.", "content": "Tumors involving the submandibular gland are rare. However, the incidence of malignancy is much higher than in the parotid (approaching 50 percent). In addition, the 5-year survival rate in patients with malignant tumors of the submandibular gland is much poorer in our series--28 percent versus 71.8 percent for the parotid gland. Because of the poor prognosis in patients with malignant tumors involving the submandibular gland we feel that composite resections should be carried out for all tumors except low-grade mucoepidermoid tumors. In addition, postoperative radiation should be given for specific indications (detailed in the article).", "contents": "Submandibular gland tumors. Tumors involving the submandibular gland are rare. However, the incidence of malignancy is much higher than in the parotid (approaching 50 percent). In addition, the 5-year survival rate in patients with malignant tumors of the submandibular gland is much poorer in our series--28 percent versus 71.8 percent for the parotid gland. Because of the poor prognosis in patients with malignant tumors involving the submandibular gland we feel that composite resections should be carried out for all tumors except low-grade mucoepidermoid tumors. In addition, postoperative radiation should be given for specific indications (detailed in the article)."}
{"id": "PMID:202981", "title": "[Measurement of muscle reflex time in radicular disorders of the lumbosacral region].", "content": "The results of studies performed by the authors show that time measurements of proprioceptive muscular reflexes (triceps surae and tibialis posterior reflexes) may be considered a valuable addition to methods of topical diagnosis of radicular disturbances in the lumbosacral region. The reflexes were tested in twenty normal subjects. There were found an intraindividual constancy of the respective reflex time with a maximum deviation of 2 ms as well as a lateral variability up to 1.3 ms. Radicular compressions resulted in an increase in reflex time by 2 to 66 ms or failure of the reflex potential to be recorded. The pathological cases were compared with clinical and neurological studies, positive myelographies using radiopaque substances, and results of surgical operations. Compared with the results of surgical operations, changes in reflex time indicated damage to the reflex arc in ninety percent of the cases.", "contents": "[Measurement of muscle reflex time in radicular disorders of the lumbosacral region]. The results of studies performed by the authors show that time measurements of proprioceptive muscular reflexes (triceps surae and tibialis posterior reflexes) may be considered a valuable addition to methods of topical diagnosis of radicular disturbances in the lumbosacral region. The reflexes were tested in twenty normal subjects. There were found an intraindividual constancy of the respective reflex time with a maximum deviation of 2 ms as well as a lateral variability up to 1.3 ms. Radicular compressions resulted in an increase in reflex time by 2 to 66 ms or failure of the reflex potential to be recorded. The pathological cases were compared with clinical and neurological studies, positive myelographies using radiopaque substances, and results of surgical operations. Compared with the results of surgical operations, changes in reflex time indicated damage to the reflex arc in ninety percent of the cases."}
{"id": "PMID:202983", "title": "The functional pool of brain catecholamines: its size and turnover rate.", "content": "Behavioral data are reviewed that give evidence for an indiscriminate involvement of brain catecholamines (CA), especially dopamine (DA), in nerve function, regardless of the time elapsed from their synthesis. Critical analysis of biochemical and pharmacological studies shows that a clear-cut distribution of brain catecholamines in two compartments ['newly synthesized' (NS) and 'main storage'] is not at all established, and moreover that there is no adequate proof that the difference in turnover rates attributed to these two supposed pools is due to a preferential extraneuronal release of NS-CA during nerve function rather than to a preferential (nonfunctional) intraneuronal deamination of NS-CA, or at least of NS-DA.", "contents": "The functional pool of brain catecholamines: its size and turnover rate. Behavioral data are reviewed that give evidence for an indiscriminate involvement of brain catecholamines (CA), especially dopamine (DA), in nerve function, regardless of the time elapsed from their synthesis. Critical analysis of biochemical and pharmacological studies shows that a clear-cut distribution of brain catecholamines in two compartments ['newly synthesized' (NS) and 'main storage'] is not at all established, and moreover that there is no adequate proof that the difference in turnover rates attributed to these two supposed pools is due to a preferential extraneuronal release of NS-CA during nerve function rather than to a preferential (nonfunctional) intraneuronal deamination of NS-CA, or at least of NS-DA."}
{"id": "PMID:202984", "title": "The effects of amphetamine isomers on rotarod performance.", "content": "The amphetamine isomers impair the rotarod performance of rats in a dose-related manner, with (+)-amphetamine approximately four-times as potent as its (-)-isomer. At a rotation speed of 4 rpm, 60 min after i.p. administration, the TD50 values (mg/kg) were: (+)-amphetamine, 24 (21.9-26.4) and (-)-amphetamine, 96 (76.3-118.4), with the curves not deviating from parallelism. Coadministration of the peripheral cholinesterase inhibitor neostigmine salicylate (0.005 mg/kg) attenuated (+)-amphetamine neurotoxicity [30 (26.4-34.1)]. These results, in conjunction with previously reported effects of the drug on isolated nerve-muscle preparations, suggest that the muscle weakness produced by high doses of amphetamine may result from inhibition of transmission at the neuromuscular junction.", "contents": "The effects of amphetamine isomers on rotarod performance. The amphetamine isomers impair the rotarod performance of rats in a dose-related manner, with (+)-amphetamine approximately four-times as potent as its (-)-isomer. At a rotation speed of 4 rpm, 60 min after i.p. administration, the TD50 values (mg/kg) were: (+)-amphetamine, 24 (21.9-26.4) and (-)-amphetamine, 96 (76.3-118.4), with the curves not deviating from parallelism. Coadministration of the peripheral cholinesterase inhibitor neostigmine salicylate (0.005 mg/kg) attenuated (+)-amphetamine neurotoxicity [30 (26.4-34.1)]. These results, in conjunction with previously reported effects of the drug on isolated nerve-muscle preparations, suggest that the muscle weakness produced by high doses of amphetamine may result from inhibition of transmission at the neuromuscular junction."}
{"id": "PMID:202985", "title": "Viloxazine, sleep, and subjective feelings.", "content": "The sleep of eight volunteers (mean age 55) was recorded electrophysiologically while viloxazine 200 mg was taken daily for 3 weeks, preceded and followed by a week of matching blanks. The volunteers also made ratings of their feelings on visual analogue scales. Another 15 volunteers (mean age 34) took viloxazine 300 mg daily for 3 weeks, preceded and followed by 3 weeks of matching blanks, and they also made daily ratings of feelings. The drug diminished sleep duration and caused more frequent and longer transitions into wakefulness and drowsiness. Slow-wave sleep decreased and stage 2 increased. REM sleep was markedly reduced, especially initially, and there was a withdrawal rebound. Viloxazine impaired subjective concentration mood, and quality of sleep. Three volunteers, however, had striking mood elevation. The drug caused a small loss of weight, which correlated with gastrointestinal symptoms. Three older subjects experienced withdrawal vomiting and prostration. Viloxazine shares properties with imipramine and with amphetamines.", "contents": "Viloxazine, sleep, and subjective feelings. The sleep of eight volunteers (mean age 55) was recorded electrophysiologically while viloxazine 200 mg was taken daily for 3 weeks, preceded and followed by a week of matching blanks. The volunteers also made ratings of their feelings on visual analogue scales. Another 15 volunteers (mean age 34) took viloxazine 300 mg daily for 3 weeks, preceded and followed by 3 weeks of matching blanks, and they also made daily ratings of feelings. The drug diminished sleep duration and caused more frequent and longer transitions into wakefulness and drowsiness. Slow-wave sleep decreased and stage 2 increased. REM sleep was markedly reduced, especially initially, and there was a withdrawal rebound. Viloxazine impaired subjective concentration mood, and quality of sleep. Three volunteers, however, had striking mood elevation. The drug caused a small loss of weight, which correlated with gastrointestinal symptoms. Three older subjects experienced withdrawal vomiting and prostration. Viloxazine shares properties with imipramine and with amphetamines."}
{"id": "PMID:202986", "title": "Time-dependent disruptive effects of apomorphine and alpha-methyl-p-tyrosine on development of morphine tolerance.", "content": "In rats the development of one-trial tolerance to the analgesic action of i.p. administered morphine is disrupted by the postadministration of apomorphine (30 mg/kg at 5 min but not at 3 h) or alpha-methyl-p-tyrosine (200 mg/kg at 5 min and 3 h but not at 12 h). Diethyldithiocarbamate or propranol has no disruptive effect. It is suggested that development of tolerance to the analgesic effects of morphine is mediated by sequential time-dependent biochemical processes.", "contents": "Time-dependent disruptive effects of apomorphine and alpha-methyl-p-tyrosine on development of morphine tolerance. In rats the development of one-trial tolerance to the analgesic action of i.p. administered morphine is disrupted by the postadministration of apomorphine (30 mg/kg at 5 min but not at 3 h) or alpha-methyl-p-tyrosine (200 mg/kg at 5 min and 3 h but not at 12 h). Diethyldithiocarbamate or propranol has no disruptive effect. It is suggested that development of tolerance to the analgesic effects of morphine is mediated by sequential time-dependent biochemical processes."}
{"id": "PMID:202987", "title": "[Sleep changes induced by chronic administration of S. 1694 (Survector) (author's transl)].", "content": "Five adult Macaca mulatta were studied during chronic administration (24 days) of S. 1694 (10 mg/kg, i.m.). This substance induced a significant increase of the first awakening (delaying sleep onset) and an enhancement of the duration of REM and stage 4 sleep. After withdrawal, the waking effect desappeared, but the increase in stage 4 sleep was maintained for one week and REM enhancement kept rising for 15 days. This observation of long-term action underlined the validity of drug experiments in chronic treatment: S. 1694 might set a new type of monoaminergic systems regulation.", "contents": "[Sleep changes induced by chronic administration of S. 1694 (Survector) (author's transl)]. Five adult Macaca mulatta were studied during chronic administration (24 days) of S. 1694 (10 mg/kg, i.m.). This substance induced a significant increase of the first awakening (delaying sleep onset) and an enhancement of the duration of REM and stage 4 sleep. After withdrawal, the waking effect desappeared, but the increase in stage 4 sleep was maintained for one week and REM enhancement kept rising for 15 days. This observation of long-term action underlined the validity of drug experiments in chronic treatment: S. 1694 might set a new type of monoaminergic systems regulation."}
{"id": "PMID:202988", "title": "Secretion of hormones influencing water and electrolyte balance (antidiuretic hormone, aldosterone, prolactin) during sleep in normal adult men.", "content": "Renal conservation of electrolytes and water occurs normally during sleep. Antidiuretic hormone (ADH), aldosterone (ALDO), and prolactin (PRL) are hormones that may have interactive effects on kidney function. The availability of a radioimmunoassay for ADH as well as for ALDO and PRL permitted the study of the simultaneous secretion patterns of these three hormones during all-night sleep in eight normal young adult men, by blood sampling every 20 min from 2300 to 0700 on two consecutive night. ADH, ALDO, and PRL all appeared to be secreted episodically. The pulsatile release of ADH was random, and average plasma ADH levels were unchanged during the night. ALDO and PRL, on the other hand, had an approximately 90-min secretion rhythm, and average plasma concentrations of both hormones consistently increased during the hours of sleep. Average plasma sodium concentration was constant throughout the night. The nocturnal increase in plasma ALDO may be responsible for the normal reduction of urine sodium excretion during the night. The concomitant increase in plasma PRL might synergize with ALDO in influencing the renal retention of sodium, but PRL alone has little apparent effect on human kidney function. REM sleep-related decreases in urine flow have been noted both in humans and in monkeys, but ADH secretion was not REM related in out subjects. Autonomic activation during REM is one possible explanation for decreased urine flow during this stage of sleep.", "contents": "Secretion of hormones influencing water and electrolyte balance (antidiuretic hormone, aldosterone, prolactin) during sleep in normal adult men. Renal conservation of electrolytes and water occurs normally during sleep. Antidiuretic hormone (ADH), aldosterone (ALDO), and prolactin (PRL) are hormones that may have interactive effects on kidney function. The availability of a radioimmunoassay for ADH as well as for ALDO and PRL permitted the study of the simultaneous secretion patterns of these three hormones during all-night sleep in eight normal young adult men, by blood sampling every 20 min from 2300 to 0700 on two consecutive night. ADH, ALDO, and PRL all appeared to be secreted episodically. The pulsatile release of ADH was random, and average plasma ADH levels were unchanged during the night. ALDO and PRL, on the other hand, had an approximately 90-min secretion rhythm, and average plasma concentrations of both hormones consistently increased during the hours of sleep. Average plasma sodium concentration was constant throughout the night. The nocturnal increase in plasma ALDO may be responsible for the normal reduction of urine sodium excretion during the night. The concomitant increase in plasma PRL might synergize with ALDO in influencing the renal retention of sodium, but PRL alone has little apparent effect on human kidney function. REM sleep-related decreases in urine flow have been noted both in humans and in monkeys, but ADH secretion was not REM related in out subjects. Autonomic activation during REM is one possible explanation for decreased urine flow during this stage of sleep."}
{"id": "PMID:202991", "title": "Angiography in the diagnosis of liver disease in children.", "content": "75 angiographic examinations were done in 64 children aged 1 day to 16 years; 41 with various liver diseases and 23 with normal lives. The angiographic diagnosis was accurate in 95% of 44 patients where proof was established by surgery and/or biopsy. Properly used hepatic angiography is a reasonably safe procedure of great value in diagnosing and planning the surgical management of liver masses. It is also a useful tool in the diagnosis of diffuse hepatic processes of neoplastic, inflammatory or degenerative origin.", "contents": "Angiography in the diagnosis of liver disease in children. 75 angiographic examinations were done in 64 children aged 1 day to 16 years; 41 with various liver diseases and 23 with normal lives. The angiographic diagnosis was accurate in 95% of 44 patients where proof was established by surgery and/or biopsy. Properly used hepatic angiography is a reasonably safe procedure of great value in diagnosing and planning the surgical management of liver masses. It is also a useful tool in the diagnosis of diffuse hepatic processes of neoplastic, inflammatory or degenerative origin."}
{"id": "PMID:202993", "title": "[The influence of renal artery occlusion on tumor growth of experimental nephroblastomas (author's transl)].", "content": "Nephroblastomas are induced in rats with N-Methyl-N-Nitroso-Urea, and selective renal artery occlusion is performed. This procedure has the same effect like occlusion by embolization. The effect of renal artery occlusion on the growth rate of nephroblastmas is controlled by angiography and gross and microscopic examinations up to 70 days following ischemia, the results are compared with a group of untreated nephroblastoma rats. There is a marked reduction of tumor size and a decrease in tumor proliferation. There is an immediate tumor cell death induced by acute and complete ischemia. Collateral blood vessels cause residual arterial blood supply of tumor parenchyma. There seems to be a correlation between collateral blood delivery and tumor size. Even 70 days after permanent ischemia there are areas of obviously absolute normal tumor cells. The conclusion of this experimental study demonstrated that growth rate of tumors can be reduced by ischemia although potentially malignancy still remains. Clinical embolization therapy is justified only in nonoperable patients with hypernephroma and with massive hematuria.", "contents": "[The influence of renal artery occlusion on tumor growth of experimental nephroblastomas (author's transl)]. Nephroblastomas are induced in rats with N-Methyl-N-Nitroso-Urea, and selective renal artery occlusion is performed. This procedure has the same effect like occlusion by embolization. The effect of renal artery occlusion on the growth rate of nephroblastmas is controlled by angiography and gross and microscopic examinations up to 70 days following ischemia, the results are compared with a group of untreated nephroblastoma rats. There is a marked reduction of tumor size and a decrease in tumor proliferation. There is an immediate tumor cell death induced by acute and complete ischemia. Collateral blood vessels cause residual arterial blood supply of tumor parenchyma. There seems to be a correlation between collateral blood delivery and tumor size. Even 70 days after permanent ischemia there are areas of obviously absolute normal tumor cells. The conclusion of this experimental study demonstrated that growth rate of tumors can be reduced by ischemia although potentially malignancy still remains. Clinical embolization therapy is justified only in nonoperable patients with hypernephroma and with massive hematuria."}
{"id": "PMID:203002", "title": "Postoperative nonspecific immunotherapy in primary bronchogenic carcinoma.", "content": "A postoperative active nonspecific immunotherapy has been conducted in 54 patients operated on for primary bronchogenic carcinoma. The immunopotentiator used is an original product prepared from a transformed strain of a saprophytic mycobacterium: M. smegmatis ATCC 607. The patients treated show an increase in postoperative survival rates of 60% at 1 year and 50% at 2 years, with regard to the survival rates of a control group and 21 surgical series available totaling over 20,000 patients. This important increase in the survival rates is accompanied by an appreciable improvement in patient comfort.", "contents": "Postoperative nonspecific immunotherapy in primary bronchogenic carcinoma. A postoperative active nonspecific immunotherapy has been conducted in 54 patients operated on for primary bronchogenic carcinoma. The immunopotentiator used is an original product prepared from a transformed strain of a saprophytic mycobacterium: M. smegmatis ATCC 607. The patients treated show an increase in postoperative survival rates of 60% at 1 year and 50% at 2 years, with regard to the survival rates of a control group and 21 surgical series available totaling over 20,000 patients. This important increase in the survival rates is accompanied by an appreciable improvement in patient comfort."}
{"id": "PMID:203010", "title": "[Respiratory gas exchange during breathing of O2 in different inert gases (author's transl)].", "content": "In 15 patients with chronic bronchitis with or without emphysema breathing of room air was compared with breathing of 20.9% O2 in helium and in argon. Minute ventilation and alveolar ventilation showed no differences, whereas the alveolar and arterial pO2 and PCO2 showed an improvement of the CO2 gas exchange and a deterioration of the O2 gas exchange. This contradictory behaviour cannot be explained by shunts or inhomogeneities or influence of gaseous or alveolo-capillary diffusion. Perhaps the physicochemical properties of the alveolo-capillary membrane change by the depletion of nitrogen. The recommendation of helium-oxygen breathing, proposed by other authors for patients with obstructive airway diseases, cannot be supported, when the gas exchange for O2 is deteriorated.", "contents": "[Respiratory gas exchange during breathing of O2 in different inert gases (author's transl)]. In 15 patients with chronic bronchitis with or without emphysema breathing of room air was compared with breathing of 20.9% O2 in helium and in argon. Minute ventilation and alveolar ventilation showed no differences, whereas the alveolar and arterial pO2 and PCO2 showed an improvement of the CO2 gas exchange and a deterioration of the O2 gas exchange. This contradictory behaviour cannot be explained by shunts or inhomogeneities or influence of gaseous or alveolo-capillary diffusion. Perhaps the physicochemical properties of the alveolo-capillary membrane change by the depletion of nitrogen. The recommendation of helium-oxygen breathing, proposed by other authors for patients with obstructive airway diseases, cannot be supported, when the gas exchange for O2 is deteriorated."}
{"id": "PMID:203011", "title": "Role of alpha-adrenergic receptors in exercise-induced bronchoconstriction.", "content": "The role of alpha-adrenergic receptors in exercise-induced bronchoconstriction (EIB) was studied. 9 asthmatic patients with a marked degree of EIB (group I) and 6 asthmatic patients with no or a less severe EIB (group II) were investigated and compared with 8 healthy control persons. Pulse rate, airway resistance and end-expiratory thoracic gas volume were measured at rest and immediately and 15 min after exercise. Group I subjects showed a significant inhibition of EIB after alpha-adrenergic blockade with phentolamine (10 mg as aerosol) and after cholinergic blockade with an atropine-ester (60 mg as aerosol). In 7 of 9 patients who had received phentolamine, and in 3 of 6 patients who had received atropine-ester, the EIB was completely suppressed. In group II the administration of propranolol (40 mg orally) produced a significant increase in EIB. The effect of propranolol could be inhibited by the addition of alpha-adrenergic blockade with phentolamine (10 mg as aerosol). The control subjects had no measurable EIB, even after the administration of propranolol (40 mg orally). It is concluded that, in addition to the vagal system, an activated alpha-adrenergic system is involved in the phenomenon of EIB.", "contents": "Role of alpha-adrenergic receptors in exercise-induced bronchoconstriction. The role of alpha-adrenergic receptors in exercise-induced bronchoconstriction (EIB) was studied. 9 asthmatic patients with a marked degree of EIB (group I) and 6 asthmatic patients with no or a less severe EIB (group II) were investigated and compared with 8 healthy control persons. Pulse rate, airway resistance and end-expiratory thoracic gas volume were measured at rest and immediately and 15 min after exercise. Group I subjects showed a significant inhibition of EIB after alpha-adrenergic blockade with phentolamine (10 mg as aerosol) and after cholinergic blockade with an atropine-ester (60 mg as aerosol). In 7 of 9 patients who had received phentolamine, and in 3 of 6 patients who had received atropine-ester, the EIB was completely suppressed. In group II the administration of propranolol (40 mg orally) produced a significant increase in EIB. The effect of propranolol could be inhibited by the addition of alpha-adrenergic blockade with phentolamine (10 mg as aerosol). The control subjects had no measurable EIB, even after the administration of propranolol (40 mg orally). It is concluded that, in addition to the vagal system, an activated alpha-adrenergic system is involved in the phenomenon of EIB."}
{"id": "PMID:203014", "title": "[Medullary angiomas and the Klippel-Trenaunay-Weber syndrome].", "content": "5 cases of an association of Klippel-Trenaunay-Weber syndrome and of spinal cord angiomas are reported amongst a series of 150 cases of malformation of the cord. The hypertrophic element, arterial dilatations and varices were found to be constant, in constant to cutaneous angiomatosis which was found in only 2 cases. There were intraspinal angiomas in all cases. The relationship between Klippel-Trenaunay-Weber syndrome and regional angiomatous phacomatoses are discussed.", "contents": "[Medullary angiomas and the Klippel-Trenaunay-Weber syndrome]. 5 cases of an association of Klippel-Trenaunay-Weber syndrome and of spinal cord angiomas are reported amongst a series of 150 cases of malformation of the cord. The hypertrophic element, arterial dilatations and varices were found to be constant, in constant to cutaneous angiomatosis which was found in only 2 cases. There were intraspinal angiomas in all cases. The relationship between Klippel-Trenaunay-Weber syndrome and regional angiomatous phacomatoses are discussed."}
{"id": "PMID:203015", "title": "[Attempted treatment of a voluminous tympano-jugular and retropharyngeal glomus tumor by embolization].", "content": "The authors report a case of glomus tumor effectively treated by embolisation. The very large size of this tumor, the age and very poor general condition of the patient due to swallowing difficulties represented a contraindication to classical methods of treatment. Elective devascularisation was carried out by embolisation of the tumour itself using non-resorbable inert material by way of selective catheterisation of the vessels supplying it, almost all of which arose from the external carotid. Rapid and durable disappearance of part of the left cranial nerve involvement, in particular swallowing difficulties, reflected the effectiveness of the method. 18 months after this attempt at palliative treatment, the patient's condition remains satisfactory, with no detectable evidence of any recurrence or progression of the tumour.", "contents": "[Attempted treatment of a voluminous tympano-jugular and retropharyngeal glomus tumor by embolization]. The authors report a case of glomus tumor effectively treated by embolisation. The very large size of this tumor, the age and very poor general condition of the patient due to swallowing difficulties represented a contraindication to classical methods of treatment. Elective devascularisation was carried out by embolisation of the tumour itself using non-resorbable inert material by way of selective catheterisation of the vessels supplying it, almost all of which arose from the external carotid. Rapid and durable disappearance of part of the left cranial nerve involvement, in particular swallowing difficulties, reflected the effectiveness of the method. 18 months after this attempt at palliative treatment, the patient's condition remains satisfactory, with no detectable evidence of any recurrence or progression of the tumour."}
{"id": "PMID:203022", "title": "Urinary cyclic adenosine 3',5'-monophosphate excretion in children in short stature: effect of somatotropin.", "content": "Excretion of urinary cyclic adenosine 3',5'-monophosphate (cAMP) was determined in twenty-four children of short stature and in sixteen normal children. Of the patients, eight suffered from anterior panhypopituitarism, six from isolated deficiency or somatotropin, seven had a family history of short stature, and three had growth failure of pre-natal onset. In children suffering from anterior panhypopituitarism or from isolated somatotropin deficiency, excretion of cAMP was found to be depressed. Short-term administration of purified somatotropin in normal therapeutic dose (3.4 mg per 1.7 m2 i.m. daily for 5 days) had no effect on urinary cAMP, but reduced urine volume in all patient groups. During somatotropin treatment there was a positive correlation between changes in urine volume and nitrogen balance (r = 0.67).", "contents": "Urinary cyclic adenosine 3',5'-monophosphate excretion in children in short stature: effect of somatotropin. Excretion of urinary cyclic adenosine 3',5'-monophosphate (cAMP) was determined in twenty-four children of short stature and in sixteen normal children. Of the patients, eight suffered from anterior panhypopituitarism, six from isolated deficiency or somatotropin, seven had a family history of short stature, and three had growth failure of pre-natal onset. In children suffering from anterior panhypopituitarism or from isolated somatotropin deficiency, excretion of cAMP was found to be depressed. Short-term administration of purified somatotropin in normal therapeutic dose (3.4 mg per 1.7 m2 i.m. daily for 5 days) had no effect on urinary cAMP, but reduced urine volume in all patient groups. During somatotropin treatment there was a positive correlation between changes in urine volume and nitrogen balance (r = 0.67)."}
{"id": "PMID:203018", "title": "Conventional electromyography in myotonic dystrophy.", "content": "In 31 subjects of 23 different families with unequivocal signs and symptoms of myotonic dystrophy EMG was performed with conventional technique on brachial biceps, extensor digitorum communis and tibialis anterior muscles. In 14 of these patients motor and orthodromic sensory conduction velocities were measured in median nerve as well. During full muscular effort, an interference pattern of low amplitude was seen in most of the explored muscles, while \"after discharge\" of different duration was present in 57-83% of the patients. At weak effort, mean potential duration was nearly always significantly reduced if polyphasic potentials were not included in the calculation; polyphasic potentials, however, exceeded the limits of normal incidence and their duration was longer than that of motor unit potentials of simple shape. At rest, spontaneous activity of short duration and positive sharp waves occurred in about 50% of the patients, but rarely in more than two places. Bursts of myotonic or pseudomyotonic discharges occurred either spontaneously or mechanically in all subjects. Conduction velocity along motor, or sensory, peripheral nerve fibres was constantly within normal values. Results were discussed in relation to the hypothesis of a primary neuronal pathogenesis of muscle wasting, and the conclusion was that nerve changes are to be considered as a collateral disorder dependent on the pleiotropic action of the gene.", "contents": "Conventional electromyography in myotonic dystrophy. In 31 subjects of 23 different families with unequivocal signs and symptoms of myotonic dystrophy EMG was performed with conventional technique on brachial biceps, extensor digitorum communis and tibialis anterior muscles. In 14 of these patients motor and orthodromic sensory conduction velocities were measured in median nerve as well. During full muscular effort, an interference pattern of low amplitude was seen in most of the explored muscles, while \"after discharge\" of different duration was present in 57-83% of the patients. At weak effort, mean potential duration was nearly always significantly reduced if polyphasic potentials were not included in the calculation; polyphasic potentials, however, exceeded the limits of normal incidence and their duration was longer than that of motor unit potentials of simple shape. At rest, spontaneous activity of short duration and positive sharp waves occurred in about 50% of the patients, but rarely in more than two places. Bursts of myotonic or pseudomyotonic discharges occurred either spontaneously or mechanically in all subjects. Conduction velocity along motor, or sensory, peripheral nerve fibres was constantly within normal values. Results were discussed in relation to the hypothesis of a primary neuronal pathogenesis of muscle wasting, and the conclusion was that nerve changes are to be considered as a collateral disorder dependent on the pleiotropic action of the gene."}
{"id": "PMID:203023", "title": "Isolation and partial characterization of a glycine- and serine-rich polypeptide from human serum high-density lipoproteins (HDL).", "content": "Lately, several minor polypeptides characterized by a high content of glycine and serum have been described in human serum lipoproteins. By column chromatography we have isolated a glycine- and serine-rich polypeptide from totally delipidized high-density lipoproteins, apo-HDL. The partial characterization of this polypeptide by total amino acid composition and by immunology utilizing monospecific antisera to polypeptides of human serum lipoproteins, would indicate a unique polypeptide. This low molecular weight (4900 Daltons) glycine- and serine-rich polypeptide was characterized by a mobility on polyacrylamide gel electrophoresis, similar to that of polypeptide. A-I, a blocked NH2-terminal amino acid and a terminal COOH-fragment consisting of R-Ser-Ala-Gly-Gly. There are similarities between this polypeptide and the protein moiety of a cholesterol ester-rich lipoprotein fraction, HDLsup, obtained by in vitro incubation of HDL subfractions and described in earlier publications by our group. The identity between these two polypeptides, cannot be confirmed by the present study.", "contents": "Isolation and partial characterization of a glycine- and serine-rich polypeptide from human serum high-density lipoproteins (HDL). Lately, several minor polypeptides characterized by a high content of glycine and serum have been described in human serum lipoproteins. By column chromatography we have isolated a glycine- and serine-rich polypeptide from totally delipidized high-density lipoproteins, apo-HDL. The partial characterization of this polypeptide by total amino acid composition and by immunology utilizing monospecific antisera to polypeptides of human serum lipoproteins, would indicate a unique polypeptide. This low molecular weight (4900 Daltons) glycine- and serine-rich polypeptide was characterized by a mobility on polyacrylamide gel electrophoresis, similar to that of polypeptide. A-I, a blocked NH2-terminal amino acid and a terminal COOH-fragment consisting of R-Ser-Ala-Gly-Gly. There are similarities between this polypeptide and the protein moiety of a cholesterol ester-rich lipoprotein fraction, HDLsup, obtained by in vitro incubation of HDL subfractions and described in earlier publications by our group. The identity between these two polypeptides, cannot be confirmed by the present study."}
{"id": "PMID:203024", "title": "Family infections by reo-like virus. Comparison of antibody titres by complement fixation and immunoelectroosmophoresis.", "content": "The families of 31 index cases infected by reo-like virus were examined for gastroenteritis symptoms, virus excretion and serological evidence of infection. Excretion of virus was seen only among the children in the families, and it occurred together with gastroenteritis symptoms in 97.2% of all cases. Virtually all infected children had a significant rise in titre in paired sera. Among the parents 25.0% had a significant rise in titre associated with infections with gastroenteritis symptoms and 28.6% with symptomfree infections. A comparison between complement fixation and immunoelectroosmophoresis for detection of antibody showed that the tests gave similar results.", "contents": "Family infections by reo-like virus. Comparison of antibody titres by complement fixation and immunoelectroosmophoresis. The families of 31 index cases infected by reo-like virus were examined for gastroenteritis symptoms, virus excretion and serological evidence of infection. Excretion of virus was seen only among the children in the families, and it occurred together with gastroenteritis symptoms in 97.2% of all cases. Virtually all infected children had a significant rise in titre in paired sera. Among the parents 25.0% had a significant rise in titre associated with infections with gastroenteritis symptoms and 28.6% with symptomfree infections. A comparison between complement fixation and immunoelectroosmophoresis for detection of antibody showed that the tests gave similar results."}
{"id": "PMID:203025", "title": "[Stress and sleep].", "content": "For this paper, psychophysiological relationships between stress and sleep are considered with reference to clinical psychiatric problems. Answers to the first question--how does sleep affect the tolerance of stress in the waking state?--are provided by sleep deprivation experiments. The latter show that total sleep deprivation has a great influence on stress. However gradual partial sleep deprivation to a sleep time of 5 hours seems well tolerated by most individuals. In some special cases we found subjects well adapted to the workaday world who could live with briefer sleeping periods. Because of experimental problems, the second question--how does stress affect sleep?--is more difficult to answer. Anxiety is one of the most important factors deteriorating sleep under conditions of stress. This reduced sleep is in turn stressful for waking behavior. Thus, the relationship between stress and sleep, two factors separated for scientific investigation, is essential and especially important in the problem of insomnia.", "contents": "[Stress and sleep]. For this paper, psychophysiological relationships between stress and sleep are considered with reference to clinical psychiatric problems. Answers to the first question--how does sleep affect the tolerance of stress in the waking state?--are provided by sleep deprivation experiments. The latter show that total sleep deprivation has a great influence on stress. However gradual partial sleep deprivation to a sleep time of 5 hours seems well tolerated by most individuals. In some special cases we found subjects well adapted to the workaday world who could live with briefer sleeping periods. Because of experimental problems, the second question--how does stress affect sleep?--is more difficult to answer. Anxiety is one of the most important factors deteriorating sleep under conditions of stress. This reduced sleep is in turn stressful for waking behavior. Thus, the relationship between stress and sleep, two factors separated for scientific investigation, is essential and especially important in the problem of insomnia."}
{"id": "PMID:203027", "title": "[Demonstration of osseous tumor micrometastases: comparison of the value of bone marrow cytology and histology].", "content": "In the course of a complete diagnostic work up (\"staging\") of 404 patients with solid tumors and malignant lymphomas, the bone marrow (BM) was analyzed cytologically (smears) as well as histologically (needle biopsy). 1. In this study both smear and needle biopsy showed an equal percentage of tumor metastases in the BM (14.6% and 16.1% respectively). Considerable differences exist between the various kinds of tumors, and therefore, each type must be viewed separately. 2. BM smear and BM needle biopsy complement each other. Combination of the two shows approximately 20--30% more positive BM finding as compared to each of the methods alone (19.6% positive findings), execpt in Hodgkin's disease.3. In Hodgkin's disease BM biopsy is superior to the smear in detecting BM infiltration. The biopsy yield is not improved on by smear. 4. In patients with oat cell tumors of the lung, the BM smears appear to be superior to biopsy for diagnosis of marrow invasion. The diagnostic yield of BM smears is, however, supplemented by the histology of simultaneous BM needle biopsy. 5. Direct BM examination (smear and needle biopsy) effectively supplements diagnostic radiological and isotope scanning procedures of the skeleton in searching for disseminated BM metastases in lung cancer of the oat-cell type, in non-Hodgkin lymphomas, and in prostatic cancer, but does not do so in patients with other solid tumors and Hodgkin's disease.", "contents": "[Demonstration of osseous tumor micrometastases: comparison of the value of bone marrow cytology and histology]. In the course of a complete diagnostic work up (\"staging\") of 404 patients with solid tumors and malignant lymphomas, the bone marrow (BM) was analyzed cytologically (smears) as well as histologically (needle biopsy). 1. In this study both smear and needle biopsy showed an equal percentage of tumor metastases in the BM (14.6% and 16.1% respectively). Considerable differences exist between the various kinds of tumors, and therefore, each type must be viewed separately. 2. BM smear and BM needle biopsy complement each other. Combination of the two shows approximately 20--30% more positive BM finding as compared to each of the methods alone (19.6% positive findings), execpt in Hodgkin's disease.3. In Hodgkin's disease BM biopsy is superior to the smear in detecting BM infiltration. The biopsy yield is not improved on by smear. 4. In patients with oat cell tumors of the lung, the BM smears appear to be superior to biopsy for diagnosis of marrow invasion. The diagnostic yield of BM smears is, however, supplemented by the histology of simultaneous BM needle biopsy. 5. Direct BM examination (smear and needle biopsy) effectively supplements diagnostic radiological and isotope scanning procedures of the skeleton in searching for disseminated BM metastases in lung cancer of the oat-cell type, in non-Hodgkin lymphomas, and in prostatic cancer, but does not do so in patients with other solid tumors and Hodgkin's disease."}
{"id": "PMID:203028", "title": "[The when and how of therapy for hyperlipoproteinemia].", "content": "Hyperlipoproteinemia is found in about 10--15% of the adult population. There is a strong correlation between elevated total and LDL cholesterol levels, decreased HDL cholesterol values and the incidence of coronary heart disease. Large-scale screening for this strong risk factor should be initiated at an early stage, when possible even in childhood. Dietary treatment is the basis of all lipid-lowering therapy. Lipid-lowering drugs should be given only in addition to a carefully controlled diet. Dietary and drug treatment of hyperlipoproteinemia is discussed.", "contents": "[The when and how of therapy for hyperlipoproteinemia]. Hyperlipoproteinemia is found in about 10--15% of the adult population. There is a strong correlation between elevated total and LDL cholesterol levels, decreased HDL cholesterol values and the incidence of coronary heart disease. Large-scale screening for this strong risk factor should be initiated at an early stage, when possible even in childhood. Dietary treatment is the basis of all lipid-lowering therapy. Lipid-lowering drugs should be given only in addition to a carefully controlled diet. Dietary and drug treatment of hyperlipoproteinemia is discussed."}
{"id": "PMID:203029", "title": "[Experimental basis for the therapy of Amanita phalloides poisoning].", "content": "The experimental basis for the treatment of death-cap poisoning is reviewed. The available data suggest penicillin and silymarin as the antidotes most likely to be effective. Measures to increase the elimination of the toxins appear to be warranted.", "contents": "[Experimental basis for the therapy of Amanita phalloides poisoning]. The experimental basis for the treatment of death-cap poisoning is reviewed. The available data suggest penicillin and silymarin as the antidotes most likely to be effective. Measures to increase the elimination of the toxins appear to be warranted."}
{"id": "PMID:203031", "title": "Sodium requirement for the positive inotropic action of isoproterenol on guinea pig atria.", "content": "Isoproterenol doses not elicit its characteristic positive inotropic action in contracting guinea pig atria suspended in sodium-free media. However, the ability of isoproterenol to decrease the time to peak tension development during an individual contraction cycle is still present in sodium-free solutions. Removal of sodium diminished but did not eliminate the tissues' ability to elevate adenosine 3',5'-monophosphate in response to isoproterenol. The striking absence of an inotropic action by isoproterenol on atria in sodium-free media suggests that sodium (and possibly a sodium-calcium exchange across the sarcolemma) plays an important role in the inotropic action of catecholamines.", "contents": "Sodium requirement for the positive inotropic action of isoproterenol on guinea pig atria. Isoproterenol doses not elicit its characteristic positive inotropic action in contracting guinea pig atria suspended in sodium-free media. However, the ability of isoproterenol to decrease the time to peak tension development during an individual contraction cycle is still present in sodium-free solutions. Removal of sodium diminished but did not eliminate the tissues' ability to elevate adenosine 3',5'-monophosphate in response to isoproterenol. The striking absence of an inotropic action by isoproterenol on atria in sodium-free media suggests that sodium (and possibly a sodium-calcium exchange across the sarcolemma) plays an important role in the inotropic action of catecholamines."}
{"id": "PMID:203032", "title": "Rearing regimen producing piglet diarrhea (rotavirus) and its relevance to acute infantile diarrhea.", "content": "Piglets were weaned when 1 day old and thus were denied further access to the antibodies supplied by their dam's milk. They were placed in a nursery in which contamination by the ubiquitous rotavirus steadily increased with continuous use causing a progressive increase in the incidence of vomiting, diarrhea, and death among the piglets. A similar syndrome involving an antigenically related rotavirus and analogous management practices occurs in human infants.", "contents": "Rearing regimen producing piglet diarrhea (rotavirus) and its relevance to acute infantile diarrhea. Piglets were weaned when 1 day old and thus were denied further access to the antibodies supplied by their dam's milk. They were placed in a nursery in which contamination by the ubiquitous rotavirus steadily increased with continuous use causing a progressive increase in the incidence of vomiting, diarrhea, and death among the piglets. A similar syndrome involving an antigenically related rotavirus and analogous management practices occurs in human infants."}
{"id": "PMID:203033", "title": "Serum lipoprotein concentrations in cystic fibrosis.", "content": "Two major classes of lipoproteins, low density and high density, are decreased in the serum of patients with cystic fibrosis; major apoproteins are also decreased. Since essential fatty acids and certain fat-soluble vitamins depend on lipoproteins for transport in the serum, knowledge of lipoprotein levels in cystic fibrosis patients could prove valuable in understanding (i) the basis for the abnormally low serum levels of these fatty acids and vitamins and (ii) the effects of therapies involving these molecules.", "contents": "Serum lipoprotein concentrations in cystic fibrosis. Two major classes of lipoproteins, low density and high density, are decreased in the serum of patients with cystic fibrosis; major apoproteins are also decreased. Since essential fatty acids and certain fat-soluble vitamins depend on lipoproteins for transport in the serum, knowledge of lipoprotein levels in cystic fibrosis patients could prove valuable in understanding (i) the basis for the abnormally low serum levels of these fatty acids and vitamins and (ii) the effects of therapies involving these molecules."}
{"id": "PMID:203034", "title": "Biologically active pituitary hormones in the rat brain amygdaloid nucleus.", "content": "While an attempt was being made to identify the source of the growth hormone releasing factor present in cerebral spinal fluid of man, it was discovered that cells of the rat amygdaloid nucleus, grown in tissue culture, produce a material that is immunologically and chromatographically identical to growth hormone found in the pituitary. Immunoperoxidase staining revealed dense accumulation of the peroxidase-antibody to growth hormone complex in amygdala cells. Significant amounts of growth hormone and adrenocorticotropin could be extracted from this limbic structure. Extracts containing immunoequivalent amounts of growth hormone were measured by bioassay in hypophysectomized rats. Stimulation of the growth of epiphyseal cartilage by extracts of the amygdala was comparable to the stimulation by extracts of anterior pituitary glands. The stimulatory effect of amygdala extracts on adrenal and gonadal size and weight and on growth of thyroid follicular epithelium was also comparable to that of pituitary extracts.", "contents": "Biologically active pituitary hormones in the rat brain amygdaloid nucleus. While an attempt was being made to identify the source of the growth hormone releasing factor present in cerebral spinal fluid of man, it was discovered that cells of the rat amygdaloid nucleus, grown in tissue culture, produce a material that is immunologically and chromatographically identical to growth hormone found in the pituitary. Immunoperoxidase staining revealed dense accumulation of the peroxidase-antibody to growth hormone complex in amygdala cells. Significant amounts of growth hormone and adrenocorticotropin could be extracted from this limbic structure. Extracts containing immunoequivalent amounts of growth hormone were measured by bioassay in hypophysectomized rats. Stimulation of the growth of epiphyseal cartilage by extracts of the amygdala was comparable to the stimulation by extracts of anterior pituitary glands. The stimulatory effect of amygdala extracts on adrenal and gonadal size and weight and on growth of thyroid follicular epithelium was also comparable to that of pituitary extracts."}
{"id": "PMID:203035", "title": "Transovarial transmission of Japanese encephalitis virus by mosquitoes.", "content": "Female Aedes albopictus and Aedes togoi mosquitoes infected with Japanese encephalitis virus either by intrathoracic inoculation or by ingestion of a virus-sucrose-erythrocyte mixture transmitted the virus to a small percentage of their F1 progeny. Adult F1 female Aedes albopictus thus infected transmitted the virus in turn to newly hatched chickens by feeding on them.", "contents": "Transovarial transmission of Japanese encephalitis virus by mosquitoes. Female Aedes albopictus and Aedes togoi mosquitoes infected with Japanese encephalitis virus either by intrathoracic inoculation or by ingestion of a virus-sucrose-erythrocyte mixture transmitted the virus to a small percentage of their F1 progeny. Adult F1 female Aedes albopictus thus infected transmitted the virus in turn to newly hatched chickens by feeding on them."}
{"id": "PMID:203036", "title": "Chick embryonic skin as a rapid organ culture assay for cellular neoplasia.", "content": "We used chick embryonic skin (CES) in organ culture to assess the neoplastic potential of a variety of cultured human and nonhuman cell lines. Cells derived from cancer tissues grew in CES and formed tumors in nude mice while cells derived from normal tissues grew in neither system. The CES proved to be more sensitive than the nude mouse when used to assay SV40 transformed human cells; each of four such lines grew in CES while only one of the four lines grew and formed tumors in nude mice. In addition, the patterns of invasion by inoculated cells can be easily studied in the CES. These results suggest that CES in organ culture offers an inexpensive, rapid, and reliable alternative to the nude mouse as a tumorigenicity test.", "contents": "Chick embryonic skin as a rapid organ culture assay for cellular neoplasia. We used chick embryonic skin (CES) in organ culture to assess the neoplastic potential of a variety of cultured human and nonhuman cell lines. Cells derived from cancer tissues grew in CES and formed tumors in nude mice while cells derived from normal tissues grew in neither system. The CES proved to be more sensitive than the nude mouse when used to assay SV40 transformed human cells; each of four such lines grew in CES while only one of the four lines grew and formed tumors in nude mice. In addition, the patterns of invasion by inoculated cells can be easily studied in the CES. These results suggest that CES in organ culture offers an inexpensive, rapid, and reliable alternative to the nude mouse as a tumorigenicity test."}
{"id": "PMID:203037", "title": "Cyclic adenosine monophosphate production by embryonic chick cells.", "content": "Cells dissociated from 1-day-old chick embryos produce a pulse of cyclic adenosine monophosphate (cyclic AMP) when stimulated with cyclic AMP. There is a stimulus threshold concentration of about 10(-8) molar cyclic AMP and an upper limit, above which the response is suppressed, of about 6 X 10(-6) molar. The response occurs within 5 seconds of stimulation and corresponds to an average pulse size in the range of 10(7) molecules per cell.", "contents": "Cyclic adenosine monophosphate production by embryonic chick cells. Cells dissociated from 1-day-old chick embryos produce a pulse of cyclic adenosine monophosphate (cyclic AMP) when stimulated with cyclic AMP. There is a stimulus threshold concentration of about 10(-8) molar cyclic AMP and an upper limit, above which the response is suppressed, of about 6 X 10(-6) molar. The response occurs within 5 seconds of stimulation and corresponds to an average pulse size in the range of 10(7) molecules per cell."}
{"id": "PMID:203038", "title": "Platelet factor 4: an inhibitor of collagenase.", "content": "Human platelet factor 4 (PF4) is known to bind to heparin and inhibit its anticoagulant effect. This factor also inhibits the enzyme collagenase derived from cultured human skin and collagenase extracted from human granulocytes. The addition of heparin to the PF4-collagenase assay system has no effect on the observed inhibition of collagenase. Thus PF4 inhibits collagenase, in addition to neutralizing heparin.", "contents": "Platelet factor 4: an inhibitor of collagenase. Human platelet factor 4 (PF4) is known to bind to heparin and inhibit its anticoagulant effect. This factor also inhibits the enzyme collagenase derived from cultured human skin and collagenase extracted from human granulocytes. The addition of heparin to the PF4-collagenase assay system has no effect on the observed inhibition of collagenase. Thus PF4 inhibits collagenase, in addition to neutralizing heparin."}
{"id": "PMID:203040", "title": "[The effect of cancer on drug metabolism and drug action].", "content": "Over the last few years, numerous studies performed mainly in animals with a tumour but also in man with malignant disease have shown that the presence of cancer modifies gastro-intestinal absorption, tissue distribution and transformation of drugs in the liver. Consequently, malignant disease also influences the therapeutic effects and toxic effects of drugs. This effect may occur with several drugs, with or without antineoplastic properties, and appears mainly at an advanced stage of the disease.", "contents": "[The effect of cancer on drug metabolism and drug action]. Over the last few years, numerous studies performed mainly in animals with a tumour but also in man with malignant disease have shown that the presence of cancer modifies gastro-intestinal absorption, tissue distribution and transformation of drugs in the liver. Consequently, malignant disease also influences the therapeutic effects and toxic effects of drugs. This effect may occur with several drugs, with or without antineoplastic properties, and appears mainly at an advanced stage of the disease."}
{"id": "PMID:203041", "title": "[The lymphocyte. Model for study of cell growth control].", "content": "The absence of one essential amino-acid during lymphocyte activation by phytohemagglutinin inhibits the synthesis of macromolecules which should normally occur. The study of the kinetics of macromolecule synthesis and RNA polymerase activity during the relief of inhibition by the addition of the deficient amino-acid, shows that partial activation occurred in spite of the absence of this essential amino-acid. We use this system of reversible inhibition of lymphocyte activation to study the role of nuclear proteins in the regulation of cell growth.", "contents": "[The lymphocyte. Model for study of cell growth control]. The absence of one essential amino-acid during lymphocyte activation by phytohemagglutinin inhibits the synthesis of macromolecules which should normally occur. The study of the kinetics of macromolecule synthesis and RNA polymerase activity during the relief of inhibition by the addition of the deficient amino-acid, shows that partial activation occurred in spite of the absence of this essential amino-acid. We use this system of reversible inhibition of lymphocyte activation to study the role of nuclear proteins in the regulation of cell growth."}
{"id": "PMID:203043", "title": "[Acute granulous leukemia in multiple myeloma. Apropos of 5 cases].", "content": "The authors report five cases of acute granular leukemia which complicated the course of multiple myeloma treated by chemotherapy. They then review the literature, and discuss 30 cases which they found. The important point clinically is the long duration of the course (average 56 months) in multiple myeloma complicated by acute granular leukemia. Usually chemotherapy permitted a good quality remission and when the leukemia develops there is no longer any trace of myeloma. The mechanisms of onset of this type of leukemia during myeloma are discussed. They are probably complex and various but there is no doubt concerning the responsability of chemotherapy and in particular alkylating agents.", "contents": "[Acute granulous leukemia in multiple myeloma. Apropos of 5 cases]. The authors report five cases of acute granular leukemia which complicated the course of multiple myeloma treated by chemotherapy. They then review the literature, and discuss 30 cases which they found. The important point clinically is the long duration of the course (average 56 months) in multiple myeloma complicated by acute granular leukemia. Usually chemotherapy permitted a good quality remission and when the leukemia develops there is no longer any trace of myeloma. The mechanisms of onset of this type of leukemia during myeloma are discussed. They are probably complex and various but there is no doubt concerning the responsability of chemotherapy and in particular alkylating agents."}
{"id": "PMID:203044", "title": "[Inagural lymphoblatic transformation in chronic myeloid leukemia. Clinical and cytogenetic study of one case].", "content": "A fifty-year old patient was treated for acute lymphoblastic leukemia. One month after a complete remission, a syndrome suggesting chronic myeloid leukemia led the authors to study the marrow karyotype which revealed the existence of a Philadelphia chromosome. A second lymphoblastic attack occurred rapidly and a second complete remission was easily obtained. A few weeks later, occurred lymphoblastic meningitis. A new cytogenetic study then showed duplication of the Philadelphia chromosome. One may imagine that the initial attack represented acute lymphoid transformation of chronic myloid leukemia. The theoretical and practical significance of this case is discussed.", "contents": "[Inagural lymphoblatic transformation in chronic myeloid leukemia. Clinical and cytogenetic study of one case]. A fifty-year old patient was treated for acute lymphoblastic leukemia. One month after a complete remission, a syndrome suggesting chronic myeloid leukemia led the authors to study the marrow karyotype which revealed the existence of a Philadelphia chromosome. A second lymphoblastic attack occurred rapidly and a second complete remission was easily obtained. A few weeks later, occurred lymphoblastic meningitis. A new cytogenetic study then showed duplication of the Philadelphia chromosome. One may imagine that the initial attack represented acute lymphoid transformation of chronic myloid leukemia. The theoretical and practical significance of this case is discussed."}
{"id": "PMID:203049", "title": "The case against routine lipoprotein electrophoresis.", "content": "We evaluate the role of lipoprotein electrophoresis as part of the routine lipogram. Analysis of 875 samples shows that it rarely provides more information than can be obtained from estimation of serum cholesterol and triglycerides with a simple test for chylomicrons. We stress the difficulties and arbitrary nature of qualitative interpretation of the electrophoretic patterns, Furthermore, electrophoretic typing is not essential for the management of patients, nor does it form the basis of current classifications of hyperlipidaemia. We argue that lipoprotein electrophoresis has a very limited place in the diagnosis and management of the individual patient.", "contents": "The case against routine lipoprotein electrophoresis. We evaluate the role of lipoprotein electrophoresis as part of the routine lipogram. Analysis of 875 samples shows that it rarely provides more information than can be obtained from estimation of serum cholesterol and triglycerides with a simple test for chylomicrons. We stress the difficulties and arbitrary nature of qualitative interpretation of the electrophoretic patterns, Furthermore, electrophoretic typing is not essential for the management of patients, nor does it form the basis of current classifications of hyperlipidaemia. We argue that lipoprotein electrophoresis has a very limited place in the diagnosis and management of the individual patient."}
{"id": "PMID:203051", "title": "Initiation of DNA synthesis and uptake of T antigen by chick erythrocyte nuclei in hterokaryons with SV40-transformed human cells.", "content": "Nonsynchronized and hydroxyurea (HU)-synchronized SV40-transformed human cells (W98VaD) were fused with chick embryo erythrocytes (CE). The uptake of T antigen by CE nuclei was compared with initiation of chick nuclear DNA synthesis. Uptake of T antigen by CE nuclei occurred at about the same time after fusion with asynchronous as with HU-synchronized cells. CE nuclei rapidly became T antigen-positive between 16 h and 28 h after fusion and usually almost all CE nuclei were T antigen-positive by 48 h after fusion. In contrast, initiation of chick nuclear DNA synthesis occurred as a function of time after reversal of the HU block, when the host cell nuclei were also synthesizing DNA. Chick nuclear DNA synthesis occurred in many heterokaryons before the CE nuclei became T antigen-positive by immunofluorescence.", "contents": "Initiation of DNA synthesis and uptake of T antigen by chick erythrocyte nuclei in hterokaryons with SV40-transformed human cells. Nonsynchronized and hydroxyurea (HU)-synchronized SV40-transformed human cells (W98VaD) were fused with chick embryo erythrocytes (CE). The uptake of T antigen by CE nuclei was compared with initiation of chick nuclear DNA synthesis. Uptake of T antigen by CE nuclei occurred at about the same time after fusion with asynchronous as with HU-synchronized cells. CE nuclei rapidly became T antigen-positive between 16 h and 28 h after fusion and usually almost all CE nuclei were T antigen-positive by 48 h after fusion. In contrast, initiation of chick nuclear DNA synthesis occurred as a function of time after reversal of the HU block, when the host cell nuclei were also synthesizing DNA. Chick nuclear DNA synthesis occurred in many heterokaryons before the CE nuclei became T antigen-positive by immunofluorescence."}
{"id": "PMID:203052", "title": "A selective system for hepatoma cells producing gluconeogenic enzymes.", "content": "Gluconeogenesis is a liver-specific pathway which permits the synthesis of phosphorylated sugars from oxaloacetate, pyruvate, amino acids, or trioses. The absolute requirement for glucose or an alternative hexose which characterizes most mammalian cells probably reflects an inablility to perform gluconeogenesis rather than to generate sufficient energy by respiration alone. Cells of diverse histogenetic origins have been tested in glucose-free medium, supplemented with oxaloacetate or with dihydroxyacetone. The only cells able to grow are well-differentiated hepatoma cells which produce the relevant gluconeogenic enzymes: phosphoenolpyruvate carboxykinase, fructose diphosphatase, and triokinase. Reconstruction experiments demonstrate that glucose-free media permit the selective growth of cells producing gluconeogenic enzymes. These media should be useful for analysis of reexpression of differentiated functions in somatic cell hybrids and for the isolation of mutants.", "contents": "A selective system for hepatoma cells producing gluconeogenic enzymes. Gluconeogenesis is a liver-specific pathway which permits the synthesis of phosphorylated sugars from oxaloacetate, pyruvate, amino acids, or trioses. The absolute requirement for glucose or an alternative hexose which characterizes most mammalian cells probably reflects an inablility to perform gluconeogenesis rather than to generate sufficient energy by respiration alone. Cells of diverse histogenetic origins have been tested in glucose-free medium, supplemented with oxaloacetate or with dihydroxyacetone. The only cells able to grow are well-differentiated hepatoma cells which produce the relevant gluconeogenic enzymes: phosphoenolpyruvate carboxykinase, fructose diphosphatase, and triokinase. Reconstruction experiments demonstrate that glucose-free media permit the selective growth of cells producing gluconeogenic enzymes. These media should be useful for analysis of reexpression of differentiated functions in somatic cell hybrids and for the isolation of mutants."}
{"id": "PMID:203053", "title": "Expression of differentiated functions in hepatoma cell hybrids: selection in glucose-free media of segregated hybrid cells which reexpress gluconeogenic enzymes.", "content": "Selective glucose-free media have been used to study the reexpression of liver-specific gluconeogenic enzymes in rat hepatoma X mouse lymphoblastoma somatic hybrids. The utilization for gluconeogenesis of dihydroxyacetone or oxaloacetate requires two enzymes: fructose diphosphatase as well as either triokinase for the former or phosphoenolpyruvate carboxykinase for the latter. By sequential selection with these substrates, the reexpression of the three gluconeogenic enzymes has been dissociated. The reexpression of these enzymes is correlated with the loss of mouse chromosomes. In addition, the characterization of the parental forms of aldolase B, another liver-specific enzyme, shows that reexpression corresponds to the simultaneous production of the rat and mouse enzymes. These results demonstrate the chromosomal origin of extinction and suggest that activation of mouse silent genes which accompanies reexpression can occur without loss of the parental determinations. The hypothesis that determination involves regulatory rather than structural genes is discussed.", "contents": "Expression of differentiated functions in hepatoma cell hybrids: selection in glucose-free media of segregated hybrid cells which reexpress gluconeogenic enzymes. Selective glucose-free media have been used to study the reexpression of liver-specific gluconeogenic enzymes in rat hepatoma X mouse lymphoblastoma somatic hybrids. The utilization for gluconeogenesis of dihydroxyacetone or oxaloacetate requires two enzymes: fructose diphosphatase as well as either triokinase for the former or phosphoenolpyruvate carboxykinase for the latter. By sequential selection with these substrates, the reexpression of the three gluconeogenic enzymes has been dissociated. The reexpression of these enzymes is correlated with the loss of mouse chromosomes. In addition, the characterization of the parental forms of aldolase B, another liver-specific enzyme, shows that reexpression corresponds to the simultaneous production of the rat and mouse enzymes. These results demonstrate the chromosomal origin of extinction and suggest that activation of mouse silent genes which accompanies reexpression can occur without loss of the parental determinations. The hypothesis that determination involves regulatory rather than structural genes is discussed."}
{"id": "PMID:203056", "title": "Adenylate cyclase and phosphodiesterase activity in the platelet release abnormality.", "content": "11 patients with histories of clinical bleeding were selected as examples of platelet release abnormality. Mean bleeding time was 18 +/- 2.6 min (normal +/- SEM; 6 +/- 0.44); mean platelet adhesiveness was 9.9 +/- 4.3% (normal +/- SEM; 30 +/- 2.2). Clot retraction and platelet factor 3 were normal. Platelet aggregation with adenosine diphosphate (ADP), epinephrine and collagen was decreased, as was 14C-serotonin release. Electron microscopic studies of platelets exposed to epinephrine showed 2 subgroups: one which failed to aggregate or have centralization of organelles and a second which developed pseudopodia and centralization of organelles, but rarely aggregated or degranulated. Measurements of activity of adenylate cyclase and phosphodiesterase under basal conditions were performed on platelets from patients and control subjects. Adenylate cyclase activity was significantly lower and phosphodiesterase activity significantly higher in the patient group. Prostaglandin E1 was a potent stimulator of adenylate cyclase in both groups, as was NaF. It was concluded that the causative defects with \"platelt release abnormality\" do not reside in either the activity of adenylate cyclase or of phosphodiesterase. Changes in formation and destruction of cyclic adenosinemonophosphate (AMP) may instead be regarded as a compensatory response to a defect in another effector system.", "contents": "Adenylate cyclase and phosphodiesterase activity in the platelet release abnormality. 11 patients with histories of clinical bleeding were selected as examples of platelet release abnormality. Mean bleeding time was 18 +/- 2.6 min (normal +/- SEM; 6 +/- 0.44); mean platelet adhesiveness was 9.9 +/- 4.3% (normal +/- SEM; 30 +/- 2.2). Clot retraction and platelet factor 3 were normal. Platelet aggregation with adenosine diphosphate (ADP), epinephrine and collagen was decreased, as was 14C-serotonin release. Electron microscopic studies of platelets exposed to epinephrine showed 2 subgroups: one which failed to aggregate or have centralization of organelles and a second which developed pseudopodia and centralization of organelles, but rarely aggregated or degranulated. Measurements of activity of adenylate cyclase and phosphodiesterase under basal conditions were performed on platelets from patients and control subjects. Adenylate cyclase activity was significantly lower and phosphodiesterase activity significantly higher in the patient group. Prostaglandin E1 was a potent stimulator of adenylate cyclase in both groups, as was NaF. It was concluded that the causative defects with \"platelt release abnormality\" do not reside in either the activity of adenylate cyclase or of phosphodiesterase. Changes in formation and destruction of cyclic adenosinemonophosphate (AMP) may instead be regarded as a compensatory response to a defect in another effector system."}
{"id": "PMID:203058", "title": "[Aujeszky's disease. Studies on the possibility of differentiating between contaminated pig-breeding farms and farms on which the pigs have been inoculated with the Bartha vaccine (author's transl)].", "content": "The serological studies reported in the present paper were done on forty-one pig-breeding farms contaminated with Aujeszky's disease and four farms that were free from this disease and on which fifty per cent of the animals had been inoculated with the Bartha vaccine. The serological studies were based on the serum neutralization test (SN test). On contaminated farms, the majority of the animals present at the time of outbreak of the disease were serologically positive. Comparison of the serological findings on farms on which there had been outbreaks of the disease from two to seven and from seven to twelve months previously, showed that there was hardly any difference in titre levels between the two groups. Of twenty-eight breeding boars used for service at the time of the outbreak, twenty-one per cent were serologically negative. Serological studies in breeding gilts showed that virulent virus was only transmitted up to two months after the outbreak of the disease.", "contents": "[Aujeszky's disease. Studies on the possibility of differentiating between contaminated pig-breeding farms and farms on which the pigs have been inoculated with the Bartha vaccine (author's transl)]. The serological studies reported in the present paper were done on forty-one pig-breeding farms contaminated with Aujeszky's disease and four farms that were free from this disease and on which fifty per cent of the animals had been inoculated with the Bartha vaccine. The serological studies were based on the serum neutralization test (SN test). On contaminated farms, the majority of the animals present at the time of outbreak of the disease were serologically positive. Comparison of the serological findings on farms on which there had been outbreaks of the disease from two to seven and from seven to twelve months previously, showed that there was hardly any difference in titre levels between the two groups. Of twenty-eight breeding boars used for service at the time of the outbreak, twenty-one per cent were serologically negative. Serological studies in breeding gilts showed that virulent virus was only transmitted up to two months after the outbreak of the disease."}
{"id": "PMID:203060", "title": "HLA-D typing with an association of Dw2 and absent immune responses towards herpes simplex (type i) antigen in multiple sclerosis.", "content": "We have confirmed that HLA-Dw2 is increased in MS patients to 47% (normals 20%). Lymphocyte transformation and antibody studies with herpes simplex antigen show that many of the DW2-positive MS patients have low or absent responses. The association of low responses to HSV and the presence of Dw2 is statistically significant at a p value less than 0.01.", "contents": "HLA-D typing with an association of Dw2 and absent immune responses towards herpes simplex (type i) antigen in multiple sclerosis. We have confirmed that HLA-Dw2 is increased in MS patients to 47% (normals 20%). Lymphocyte transformation and antibody studies with herpes simplex antigen show that many of the DW2-positive MS patients have low or absent responses. The association of low responses to HSV and the presence of Dw2 is statistically significant at a p value less than 0.01."}
{"id": "PMID:203061", "title": "Isolation of living adult Onchocerca volvulus from nodules.", "content": "A technique for the isolation of adult Onchocerca volvulus from excised onchocercomata is described. The nodules are incubated in medium 199 containing 1-5 mg collagenase and 0.2 mg gentamicin per ml for 6-48 hours in a waterbath at 30-37 degrees C. A proportion of the worms can be isolated alive.", "contents": "Isolation of living adult Onchocerca volvulus from nodules. A technique for the isolation of adult Onchocerca volvulus from excised onchocercomata is described. The nodules are incubated in medium 199 containing 1-5 mg collagenase and 0.2 mg gentamicin per ml for 6-48 hours in a waterbath at 30-37 degrees C. A proportion of the worms can be isolated alive."}
{"id": "PMID:203063", "title": "Liver monoamine oxidase (MAO) in liver homogenate of mice infected with Schistosoma mansoni and effect of certain therapeutic agents.", "content": "MAO activity in liver homogenate of mice infected with Schistosoma mansoni was determined from the second till the 14th week following infection. Significant diminution of MAO activity was noticed starting from the sixth week following infection, reaching its lowest value at the eighth week, obviously denoting progress of hepatic fibrosis. Treatment of the infected, animals with four different antischistosomal agents, tarter emetic, stibophen, niridazole and hycanthone, resulted in an improvement of the enzyme level to an almost normal value. This may indicate the ease with which the lesions in the liver including fibrosis recover when the infection is successfully treated.", "contents": "Liver monoamine oxidase (MAO) in liver homogenate of mice infected with Schistosoma mansoni and effect of certain therapeutic agents. MAO activity in liver homogenate of mice infected with Schistosoma mansoni was determined from the second till the 14th week following infection. Significant diminution of MAO activity was noticed starting from the sixth week following infection, reaching its lowest value at the eighth week, obviously denoting progress of hepatic fibrosis. Treatment of the infected, animals with four different antischistosomal agents, tarter emetic, stibophen, niridazole and hycanthone, resulted in an improvement of the enzyme level to an almost normal value. This may indicate the ease with which the lesions in the liver including fibrosis recover when the infection is successfully treated."}
{"id": "PMID:203065", "title": "[Degradation and repair of rat hepatoma cell DNA following exposure to gamma rays and methylnitrosourea].", "content": "Single-strand breaks induced in DNA of ascitic hepatoma cells by gamma-rays and N-methyl-N-nitrosourea (MNU), resp., may be effectively repaired. Double-strand breaks of DNA from MNU-treated hepatoma cells are also effectively repairable in vivo. Only a small part of double-strand breaks induced by gamma-rays in DNA of these cells is repaired in the postradiation period. The combined action of gamma-rays and MNU on the hepatoma cells causes a complete inhibition of repair of DNA and its further degradation. Under these conditions, inhibition of the repair of DNA synthesis and repression of DNA polymerase I activity is observed.", "contents": "[Degradation and repair of rat hepatoma cell DNA following exposure to gamma rays and methylnitrosourea]. Single-strand breaks induced in DNA of ascitic hepatoma cells by gamma-rays and N-methyl-N-nitrosourea (MNU), resp., may be effectively repaired. Double-strand breaks of DNA from MNU-treated hepatoma cells are also effectively repairable in vivo. Only a small part of double-strand breaks induced by gamma-rays in DNA of these cells is repaired in the postradiation period. The combined action of gamma-rays and MNU on the hepatoma cells causes a complete inhibition of repair of DNA and its further degradation. Under these conditions, inhibition of the repair of DNA synthesis and repression of DNA polymerase I activity is observed."}
{"id": "PMID:203066", "title": "[Cytochemical study of different stages in the life cycle of Toxoplasma gondii. VII. Oxidation--reduction enzymes in the cyst forms].", "content": "Dehydrogenases of glycolysis, Kreb's cycle, and pentose-phosphate shunt were detected in cystozoites of Toxoplasma gondii strain SS-119 with various degrees of activity. A mixed oxidative metabolism may be postulated on this stage of the toxoplasma life cycle. Besides, the activity of cytochrome oxidase was detected in cystozoites; the addition of cytochrome c to the incubation medium significantly intensified the reaction intensity. Of interest seems the observation of a layer of higher enzymatic activity in the host brain tissue in the immediate neighbourhood with the cyst body. This may be regarded as the host cells' (or tissue') response to the presence of the parasite's alien body.", "contents": "[Cytochemical study of different stages in the life cycle of Toxoplasma gondii. VII. Oxidation--reduction enzymes in the cyst forms]. Dehydrogenases of glycolysis, Kreb's cycle, and pentose-phosphate shunt were detected in cystozoites of Toxoplasma gondii strain SS-119 with various degrees of activity. A mixed oxidative metabolism may be postulated on this stage of the toxoplasma life cycle. Besides, the activity of cytochrome oxidase was detected in cystozoites; the addition of cytochrome c to the incubation medium significantly intensified the reaction intensity. Of interest seems the observation of a layer of higher enzymatic activity in the host brain tissue in the immediate neighbourhood with the cyst body. This may be regarded as the host cells' (or tissue') response to the presence of the parasite's alien body."}
{"id": "PMID:203067", "title": "[Effect of deep freezing on isolated rat liver lysosomes].", "content": "The level of the non--sedimentating activity of acid hydrolases (deoxyribonuclease, phosphatase, cathepsins) and electron microscopy of lysosomes has been studied after freezing to --30 degrees, --70 degrees, --140 degrees and --196 degrees. It has been found that enzyme solubilistion and lysosome ultrastructure distortion are mostly marked in the temperature range between 0 degrees and --30 degrees C. Additional membrane damage is observed in the temperature range from --140 degrees to --196 degrees C. It is suggested that not only physico-chemical changes during phase transitions of free water in the freezing medium but also recrystallization processes and the freezing-out of water structurally bound with membranes may contribute to mechanism of lysosome cryoinjury.", "contents": "[Effect of deep freezing on isolated rat liver lysosomes]. The level of the non--sedimentating activity of acid hydrolases (deoxyribonuclease, phosphatase, cathepsins) and electron microscopy of lysosomes has been studied after freezing to --30 degrees, --70 degrees, --140 degrees and --196 degrees. It has been found that enzyme solubilistion and lysosome ultrastructure distortion are mostly marked in the temperature range between 0 degrees and --30 degrees C. Additional membrane damage is observed in the temperature range from --140 degrees to --196 degrees C. It is suggested that not only physico-chemical changes during phase transitions of free water in the freezing medium but also recrystallization processes and the freezing-out of water structurally bound with membranes may contribute to mechanism of lysosome cryoinjury."}
{"id": "PMID:203064", "title": "[Ultrastructure and function of zona fasciculata cells in the adrenal cortex of mice of differing genetic lines but physiologically normal].", "content": "Ultrastructure and function were studied of the cells of zona fasciculata of the adrenal cortex of male mice of strains CBA and C57B1. The results obtained point to potentially higher possibilities of the adrenal zona fasciculata in mice of strain C57B1. These data show the role of the genotype in determining the structure and functions of the cells of the adrenal cortex as well as an evident correspondence of the ultrastructural features to the specificity of functions and the level of activity of cells.", "contents": "[Ultrastructure and function of zona fasciculata cells in the adrenal cortex of mice of differing genetic lines but physiologically normal]. Ultrastructure and function were studied of the cells of zona fasciculata of the adrenal cortex of male mice of strains CBA and C57B1. The results obtained point to potentially higher possibilities of the adrenal zona fasciculata in mice of strain C57B1. These data show the role of the genotype in determining the structure and functions of the cells of the adrenal cortex as well as an evident correspondence of the ultrastructural features to the specificity of functions and the level of activity of cells."}
{"id": "PMID:203068", "title": "Epidemiologic study on enzootic bovine leukemia using serologic tests and hematologic examinations.", "content": "In order to find suitable diagnostic procedures to use in an epidemiologic survey for the detection of animals infected with the bovine leukemia virus (BLV), the authors conducted an investigation on 262 Friesian dairy cattle. The results of hematologic, serologic, and electron microscopic examinations are reported. Evaluation of the results demonstrated the validity of the immunodiffusion and immunofluorescence tests and the opportunity for their use in conjunction with examination of the blood picture. From the data reported it would appear useful to extend the investigation to the herds without history of lymphosarcoma.", "contents": "Epidemiologic study on enzootic bovine leukemia using serologic tests and hematologic examinations. In order to find suitable diagnostic procedures to use in an epidemiologic survey for the detection of animals infected with the bovine leukemia virus (BLV), the authors conducted an investigation on 262 Friesian dairy cattle. The results of hematologic, serologic, and electron microscopic examinations are reported. Evaluation of the results demonstrated the validity of the immunodiffusion and immunofluorescence tests and the opportunity for their use in conjunction with examination of the blood picture. From the data reported it would appear useful to extend the investigation to the herds without history of lymphosarcoma."}
{"id": "PMID:203069", "title": "A murine oncornavirus marker in adenovirus 7-transformed mouse cells.", "content": "The presence of oncornavirus particles in BALB/c mouse cells transformed by adenovirus 7 was investigated. The particles detected had a buoyant density of 1.16 g/cm3; both p30 and adenovirus T-specific immunofluorescence was demonstrated in the cell cytoplasm. No C-particles were shown by the electron microscope.", "contents": "A murine oncornavirus marker in adenovirus 7-transformed mouse cells. The presence of oncornavirus particles in BALB/c mouse cells transformed by adenovirus 7 was investigated. The particles detected had a buoyant density of 1.16 g/cm3; both p30 and adenovirus T-specific immunofluorescence was demonstrated in the cell cytoplasm. No C-particles were shown by the electron microscope."}
{"id": "PMID:203071", "title": "Quantitative comparison of milk-released C3H and RIII mammary tumor viruses in infected BALB/c hosts.", "content": "The C3H and RIII mammary tumor viruses (MTV) carried by BALB/cfC3H and BALB/cfRIII breeding females have been quantified and compared in milk samples, after partial purification with a sucrose density gradient. The samples were collected at identical times during the first 3 lactation periods from individual mice (6 per strain), standardized for age at delivery and size of litter. Milk samples from 6 MTV negative BALB/c controls have also been analyzed. Data for comparison are expressed in optical density units (ODU) and refer to the protein content of the whole milk using MTV-negative Balb/c milk as blank. The results have shown 1) an increase of MTV released through milk in each MTV-carrying female from the first (average ODU, 0.542) to the second (1,351) and third (2.105) lactation, 2) individual variations, and 3) a significant difference in release between C3H and RIII MTV, the latter being more than double (average ODU, 1.801) in respect to the former (0.847). The apparent discrepancy between these results and the bioactivity in BALB/c mice of C3H and RIII MTV, significantly lower for the latter, is discussed.", "contents": "Quantitative comparison of milk-released C3H and RIII mammary tumor viruses in infected BALB/c hosts. The C3H and RIII mammary tumor viruses (MTV) carried by BALB/cfC3H and BALB/cfRIII breeding females have been quantified and compared in milk samples, after partial purification with a sucrose density gradient. The samples were collected at identical times during the first 3 lactation periods from individual mice (6 per strain), standardized for age at delivery and size of litter. Milk samples from 6 MTV negative BALB/c controls have also been analyzed. Data for comparison are expressed in optical density units (ODU) and refer to the protein content of the whole milk using MTV-negative Balb/c milk as blank. The results have shown 1) an increase of MTV released through milk in each MTV-carrying female from the first (average ODU, 0.542) to the second (1,351) and third (2.105) lactation, 2) individual variations, and 3) a significant difference in release between C3H and RIII MTV, the latter being more than double (average ODU, 1.801) in respect to the former (0.847). The apparent discrepancy between these results and the bioactivity in BALB/c mice of C3H and RIII MTV, significantly lower for the latter, is discussed."}
{"id": "PMID:203070", "title": "Quantitative determination of mammary tumor virus in individual samples of mouse milk.", "content": "The possibility to determine quantitatively the intact mammary tumor virus (MTV) in milk of mice carrying milk-transmitted MTV has been assayed by a method that allows direct comparison between individual milk samples. The method is based on (a) the measure of light scattering of partially purified MTV preparations, (b) the use of milk from genetically identical MTV free mice as blank and (c) the quantitative reference to the total protein content of whole milk. The sensitivity, specificity and reproducibility of the procedure, as well as the requirement of appropriate quantitative references, are illustrated and discussed. BALB/c (MTV free), BALB/cfC3H, and BALB/cfRIII mice have been used.", "contents": "Quantitative determination of mammary tumor virus in individual samples of mouse milk. The possibility to determine quantitatively the intact mammary tumor virus (MTV) in milk of mice carrying milk-transmitted MTV has been assayed by a method that allows direct comparison between individual milk samples. The method is based on (a) the measure of light scattering of partially purified MTV preparations, (b) the use of milk from genetically identical MTV free mice as blank and (c) the quantitative reference to the total protein content of whole milk. The sensitivity, specificity and reproducibility of the procedure, as well as the requirement of appropriate quantitative references, are illustrated and discussed. BALB/c (MTV free), BALB/cfC3H, and BALB/cfRIII mice have been used."}
{"id": "PMID:203075", "title": "Nonrenovascular renal hypertension in children.", "content": "Hypertension in children has been reported with increasing frequency because of increased awareness of its occurrence by clinicians. Renovascular lesions have been stressed in the past. However, in recent years, a number of nonrenovascular renal lesions have received attention and form the basis for this report. Unilateral chronic atrophic pyelonphritis, segmental unilateral pyelonephritis, the Ask-Upmark kidney, and unilateral renal hypoplasia have been associated with curable hypertension. The subject of juxtaglomerular cell hyperplasia, which has variably been reported in these cases, is reviewed. Ureteral obstruction, in the form of uretero-pelvic or ureterovesical junction obstruction, solitary renal cysts, the unilateral multicystic kidney, renal trauma, and renal tumors (Wilms' tumor and juxtaglomerular cell tumors) may also be associated with hypertension in children. Pheochromocytoma must be ruled out in all cases. Because of renewed interest, these nonrenovascular renal causes of hypertension are now likely to be diagnosed with increased frequency.", "contents": "Nonrenovascular renal hypertension in children. Hypertension in children has been reported with increasing frequency because of increased awareness of its occurrence by clinicians. Renovascular lesions have been stressed in the past. However, in recent years, a number of nonrenovascular renal lesions have received attention and form the basis for this report. Unilateral chronic atrophic pyelonphritis, segmental unilateral pyelonephritis, the Ask-Upmark kidney, and unilateral renal hypoplasia have been associated with curable hypertension. The subject of juxtaglomerular cell hyperplasia, which has variably been reported in these cases, is reviewed. Ureteral obstruction, in the form of uretero-pelvic or ureterovesical junction obstruction, solitary renal cysts, the unilateral multicystic kidney, renal trauma, and renal tumors (Wilms' tumor and juxtaglomerular cell tumors) may also be associated with hypertension in children. Pheochromocytoma must be ruled out in all cases. Because of renewed interest, these nonrenovascular renal causes of hypertension are now likely to be diagnosed with increased frequency."}
{"id": "PMID:203076", "title": "Pathology and natural history of urethral tumors in females: review of 65 cases.", "content": "Cancer of the female urethra, although uncommon, is important because unless recognized early and treated adequately, death will ensue, preceded by much morbidity. The authors present a series of 62 patients with 70 primary tumors, and 3 patients with secondary tumors. A comprehensive classification of neoplasms of the female urethra is also included.", "contents": "Pathology and natural history of urethral tumors in females: review of 65 cases. Cancer of the female urethra, although uncommon, is important because unless recognized early and treated adequately, death will ensue, preceded by much morbidity. The authors present a series of 62 patients with 70 primary tumors, and 3 patients with secondary tumors. A comprehensive classification of neoplasms of the female urethra is also included."}
{"id": "PMID:203077", "title": "Fibrous histiocytoma of bladder.", "content": "A case of benign fibrous histiocytoma of the bladder is presented. The occurrence is rare, and criteria for defining malignant potential are unreliable. Careful follow-up evaluations are important.", "contents": "Fibrous histiocytoma of bladder. A case of benign fibrous histiocytoma of the bladder is presented. The occurrence is rare, and criteria for defining malignant potential are unreliable. Careful follow-up evaluations are important."}
{"id": "PMID:203081", "title": "[Immunofluorescence with PI-3 virus--preparation and evaluation of conjugates from immune sera of various animal species].", "content": "Immune sera with a high content of antibodies to para-influenza-3 (PI-3) virus suitable for production of specific conjugated immunoglobulins were prepared on conventionally reared calves, rabbits, and guinea-pigs, applying antigen in different ways. When processing the sera of the above mentioned animal species to conjugates, the sera differed in pure IgG yield, in completed conjugate, and molar F/P ratios, but their ability to demonstrate antigens of the PI-3 virus in the dilution was approximately the same. The serum prepared on a colostrum deprived calf showed the lowest antibody content and the lowest pure IgG yield, the colouring ability of the conjugate prepared being as well somewhat lower.", "contents": "[Immunofluorescence with PI-3 virus--preparation and evaluation of conjugates from immune sera of various animal species]. Immune sera with a high content of antibodies to para-influenza-3 (PI-3) virus suitable for production of specific conjugated immunoglobulins were prepared on conventionally reared calves, rabbits, and guinea-pigs, applying antigen in different ways. When processing the sera of the above mentioned animal species to conjugates, the sera differed in pure IgG yield, in completed conjugate, and molar F/P ratios, but their ability to demonstrate antigens of the PI-3 virus in the dilution was approximately the same. The serum prepared on a colostrum deprived calf showed the lowest antibody content and the lowest pure IgG yield, the colouring ability of the conjugate prepared being as well somewhat lower."}
{"id": "PMID:203083", "title": "[Biochemical and histological studies of cows with ketosis].", "content": "Biochemical and histological investigations were carried out with cows affected with ketosis in a subclinical and clinical form. Parellel studies were performed with normal (control) cows originating from the herds with the ill animals and manifesting the same physiologic status. It was found that the blood level of glucose in the diseased cows was lowered more than 2.6 times, and the content of ketone bodies was higher-- it was increased 4.6 times, that of total lipids was 2.6 times higher, and that of free fatty acids was 3.5 times higher as compared to the same indices in the controls. The blood content of pyruvate in the affected cows was also increased. The liver glycogen in these animals was lowered from 2.1 to 4.1 times. The activity of glucose-6-phosphatase was lower, and that of glucose-6-phosphatedehydrogenase was higher as against the same indices shown by normal cows.", "contents": "[Biochemical and histological studies of cows with ketosis]. Biochemical and histological investigations were carried out with cows affected with ketosis in a subclinical and clinical form. Parellel studies were performed with normal (control) cows originating from the herds with the ill animals and manifesting the same physiologic status. It was found that the blood level of glucose in the diseased cows was lowered more than 2.6 times, and the content of ketone bodies was higher-- it was increased 4.6 times, that of total lipids was 2.6 times higher, and that of free fatty acids was 3.5 times higher as compared to the same indices in the controls. The blood content of pyruvate in the affected cows was also increased. The liver glycogen in these animals was lowered from 2.1 to 4.1 times. The activity of glucose-6-phosphatase was lower, and that of glucose-6-phosphatedehydrogenase was higher as against the same indices shown by normal cows."}
{"id": "PMID:203086", "title": "Peripheral nervous system affection in experimental lipidosis induced by 4,4'-diethylaminoethoxyhexesterol.", "content": "A picture of generalized phosphoglyceride and cholesterol storage was induced, in keeping with literary data, by the experimental administration of 4,4'-diethylaminoethoxyhexesterol to rats. An asset of this model lies in the discovery that considerable storage occurs in the peripheral nervous system in contrast to the CNS, whose resistance to hexesterol is generally known. The significance of this finding is briefly discussed.", "contents": "Peripheral nervous system affection in experimental lipidosis induced by 4,4'-diethylaminoethoxyhexesterol. A picture of generalized phosphoglyceride and cholesterol storage was induced, in keeping with literary data, by the experimental administration of 4,4'-diethylaminoethoxyhexesterol to rats. An asset of this model lies in the discovery that considerable storage occurs in the peripheral nervous system in contrast to the CNS, whose resistance to hexesterol is generally known. The significance of this finding is briefly discussed."}
{"id": "PMID:203087", "title": "The incidence of antiviral antibodies in multiple slcerosis.", "content": "The serological investigation of 96 multiple sclerosis (MS) patients, 61 patients with various other neurological diseases and 100 healthy controls made evident the increased incident of antimeasles and antiparinfluenza type 1 antibodies in the group of \"probable\" MS patients. There was no significant difference as regards antimumps antibodies. Antimeasles antibodies were detected in 7 of the 8 cerebrospinal fluid samples from \"probable\" MS patients, but in none of the 12 samples from patients with other neurological diseases. The significance of these results for the etiology of MS is discussed.", "contents": "The incidence of antiviral antibodies in multiple slcerosis. The serological investigation of 96 multiple sclerosis (MS) patients, 61 patients with various other neurological diseases and 100 healthy controls made evident the increased incident of antimeasles and antiparinfluenza type 1 antibodies in the group of \"probable\" MS patients. There was no significant difference as regards antimumps antibodies. Antimeasles antibodies were detected in 7 of the 8 cerebrospinal fluid samples from \"probable\" MS patients, but in none of the 12 samples from patients with other neurological diseases. The significance of these results for the etiology of MS is discussed."}
{"id": "PMID:203088", "title": "Interaction between cerulopasmin and Sendai virus envelope components. Note V. Serological response in the rabbit to Sendal virus and subviral fractions.", "content": "Immunization of rabbits with Sendai virus and subviral fractions induced the appearance in the serum of both hemagglutinin- and neuraminidase-inhibiting antibodies. The study of the correlation between antigen characteristics and the level and kinetics of the antibodies suggests that a single antigenic glycoprotein carries both hemagglutinin and neuraminidase activities. The level of serum antibodies depends both on the size and structure of the antigens and on their organization, and reflects the role of the protein and carbohydrate moieties of the different antigen preparations used.", "contents": "Interaction between cerulopasmin and Sendai virus envelope components. Note V. Serological response in the rabbit to Sendal virus and subviral fractions. Immunization of rabbits with Sendai virus and subviral fractions induced the appearance in the serum of both hemagglutinin- and neuraminidase-inhibiting antibodies. The study of the correlation between antigen characteristics and the level and kinetics of the antibodies suggests that a single antigenic glycoprotein carries both hemagglutinin and neuraminidase activities. The level of serum antibodies depends both on the size and structure of the antigens and on their organization, and reflects the role of the protein and carbohydrate moieties of the different antigen preparations used."}
{"id": "PMID:203090", "title": "Parameters of RNA-dependent RNA polymerase activity in a mengovirus-infected Ehrlich ascites carcinoma cell-free system.", "content": "Virus-specific RNA polymerase activity of mengovirus-infected Ehrlich ascites carcinoma (EAC) cells was maximal 7 hours after infection in a one-step growth cycle. In a cell-free system with the mitochondrial-microsomal fraction (MMF) derived from mengovirus-infected EAC cells in a nucleoside-triphosphate medium, polymerase activity increased up to 60 min (when MMF was obtained by a homogenizer) or 120 min (when MMF was prepared by sodium deoxycholate disruption). Subsequently RNA polymerase activity decreased between 150-180 min of incubation at 37 degrees C and then formed a plateau up to 300 min. The cell-free system used is able to give valuable information as regards testing of RNA polymerase inhibitors in an antiviral screening programme.", "contents": "Parameters of RNA-dependent RNA polymerase activity in a mengovirus-infected Ehrlich ascites carcinoma cell-free system. Virus-specific RNA polymerase activity of mengovirus-infected Ehrlich ascites carcinoma (EAC) cells was maximal 7 hours after infection in a one-step growth cycle. In a cell-free system with the mitochondrial-microsomal fraction (MMF) derived from mengovirus-infected EAC cells in a nucleoside-triphosphate medium, polymerase activity increased up to 60 min (when MMF was obtained by a homogenizer) or 120 min (when MMF was prepared by sodium deoxycholate disruption). Subsequently RNA polymerase activity decreased between 150-180 min of incubation at 37 degrees C and then formed a plateau up to 300 min. The cell-free system used is able to give valuable information as regards testing of RNA polymerase inhibitors in an antiviral screening programme."}
{"id": "PMID:203103", "title": "[Soluble cerebral metalloproteins. II. Superoxide dismutases of cerebral gray and white matter].", "content": "Superoxide dismutases (SOD) of high purity have been obtained from grey and white matter of bovine brain cerebral hemispheres. The SOD obtained have been shown to have three isoenzymes (a, b, c). A study of the catalytic and macromolecular properties of the SOD obtained from grey and white matter of cerebral hemispheres as well as their optical and electron paramagnetic resonance spectra indicates that both proteins possess similar properties. The possible function of SOD in grey and white matter of brain is discussed.", "contents": "[Soluble cerebral metalloproteins. II. Superoxide dismutases of cerebral gray and white matter]. Superoxide dismutases (SOD) of high purity have been obtained from grey and white matter of bovine brain cerebral hemispheres. The SOD obtained have been shown to have three isoenzymes (a, b, c). A study of the catalytic and macromolecular properties of the SOD obtained from grey and white matter of cerebral hemispheres as well as their optical and electron paramagnetic resonance spectra indicates that both proteins possess similar properties. The possible function of SOD in grey and white matter of brain is discussed."}
{"id": "PMID:203105", "title": "[Inhibition of rat heart and brain cyclic 3',5'-adenosine monophosphate phosphodiesterase under the influence of neurohormone \"C\"].", "content": "In vitro studies of the effect of neurohormone C on cyclic AMP phosphodiesterase activity of heart and brain showed that amounts of neurohormone equal to 5 ng inhibited significantly the activity of phos-phodiestherase in heart and even more strongly in brain. A comparison of the effect of the neurohormone with that of theophylline (10 mM) showed that very small amounts of the neurohormone brought about inhibition of enzyme activity that was equal to that observed from much larger concentrations of the theophylline. It is proposed that the inhibition of phosphodiestherase activity is of importance in the mechanism of the action of the neurohormone.", "contents": "[Inhibition of rat heart and brain cyclic 3',5'-adenosine monophosphate phosphodiesterase under the influence of neurohormone \"C\"]. In vitro studies of the effect of neurohormone C on cyclic AMP phosphodiesterase activity of heart and brain showed that amounts of neurohormone equal to 5 ng inhibited significantly the activity of phos-phodiestherase in heart and even more strongly in brain. A comparison of the effect of the neurohormone with that of theophylline (10 mM) showed that very small amounts of the neurohormone brought about inhibition of enzyme activity that was equal to that observed from much larger concentrations of the theophylline. It is proposed that the inhibition of phosphodiestherase activity is of importance in the mechanism of the action of the neurohormone."}
{"id": "PMID:203113", "title": "[Pathogenesis of rhinovirus infection].", "content": "Rhinoviruses (RV) are the etiological factors of not only acute respiratory diseases of the common cold type but also of acute and chronic diseases of otorhinolaryngological organs. Virological and bacteriological examinations of patients with chronic pneumonia in the stages of exacerbation and incomplete remission revealed a high degree of the infection activity. Virus-bacterial associations were frequently found. RV were isolated from the lower respiratory tract (bronchopulmonary secrete, biopsy materials). The association of RV with the involvement of the lower respiratory tract in patients with chronic pneumonia was demonstrated. Rhinoviremia was detected in one child dying with acute respiratory disease. The results of studies on some factors of specific and nonspecific immunity in patients with chronic pneumonia are presented.", "contents": "[Pathogenesis of rhinovirus infection]. Rhinoviruses (RV) are the etiological factors of not only acute respiratory diseases of the common cold type but also of acute and chronic diseases of otorhinolaryngological organs. Virological and bacteriological examinations of patients with chronic pneumonia in the stages of exacerbation and incomplete remission revealed a high degree of the infection activity. Virus-bacterial associations were frequently found. RV were isolated from the lower respiratory tract (bronchopulmonary secrete, biopsy materials). The association of RV with the involvement of the lower respiratory tract in patients with chronic pneumonia was demonstrated. Rhinoviremia was detected in one child dying with acute respiratory disease. The results of studies on some factors of specific and nonspecific immunity in patients with chronic pneumonia are presented."}
{"id": "PMID:203118", "title": "[Effect of Production on the serum lipid and lipoprotein level in ischemic heart disease].", "content": "The serum lipids were dynamically followed up in 39 patients with ischemic heart disease treated with Prodectin. A gradual decrease of serum cholesterin is observed during the treatment period as well as of its content in alfa lipoproteins and of alfa lipoproteins themselves. A moderate decrease of triglyceride and total lipids develops in parallel with this, whereas free fatty acids considerably increase. In more than 1/3 of the patients the profile of hyperlipoproteinemia changed in the course of the treatment: the half of them turned to normolipoproteinemia, a number of the rest--into a more favourable type--II and IV type.", "contents": "[Effect of Production on the serum lipid and lipoprotein level in ischemic heart disease]. The serum lipids were dynamically followed up in 39 patients with ischemic heart disease treated with Prodectin. A gradual decrease of serum cholesterin is observed during the treatment period as well as of its content in alfa lipoproteins and of alfa lipoproteins themselves. A moderate decrease of triglyceride and total lipids develops in parallel with this, whereas free fatty acids considerably increase. In more than 1/3 of the patients the profile of hyperlipoproteinemia changed in the course of the treatment: the half of them turned to normolipoproteinemia, a number of the rest--into a more favourable type--II and IV type."}
{"id": "PMID:203114", "title": "[Chromosomes of 7 transplantable lines of macaque and pavian hematopoietic cells producing herpesvirus type EBV and oncornavirus type C].", "content": "Karyotypes of Su-1, Su-2, KMMA-1, and KMMA-2 (producing oncornavirus C-type), and KMPG-1, SPF-2, and SPG-3 (producing HSV, a virus of EBV type) cell lines were studied in the time course. The lines were derived from hemopoietic cells of brown macaques and baboons bearing lymphomas. Some of the lines had a paradiploid-pseudodiploid karyotype, another part aneuploid type. The selectivity of structural and numerical abnormalities of chromosomes 1, 9, 10, 11, 12, 13, 15, 18, and 20 was detected indicating a certain specificity of karyotype changes upon malignization and transformation. The number of poorly and moderately differentiating chromosomes in aneuploidy was confirmed by greater variability as compared with well-differentiating chromosomes. No parallelism between the karyotype change pattern and the type of virus produced (C or EBV) could be found thus far.", "contents": "[Chromosomes of 7 transplantable lines of macaque and pavian hematopoietic cells producing herpesvirus type EBV and oncornavirus type C]. Karyotypes of Su-1, Su-2, KMMA-1, and KMMA-2 (producing oncornavirus C-type), and KMPG-1, SPF-2, and SPG-3 (producing HSV, a virus of EBV type) cell lines were studied in the time course. The lines were derived from hemopoietic cells of brown macaques and baboons bearing lymphomas. Some of the lines had a paradiploid-pseudodiploid karyotype, another part aneuploid type. The selectivity of structural and numerical abnormalities of chromosomes 1, 9, 10, 11, 12, 13, 15, 18, and 20 was detected indicating a certain specificity of karyotype changes upon malignization and transformation. The number of poorly and moderately differentiating chromosomes in aneuploidy was confirmed by greater variability as compared with well-differentiating chromosomes. No parallelism between the karyotype change pattern and the type of virus produced (C or EBV) could be found thus far."}
{"id": "PMID:203115", "title": "[Virus inactivation by hydrogen peroxide].", "content": "The effect of H2O2 on adenovirus types 3 and 6, adenoassociated virus type 4, rhinoviruses 1A, 1B, and type 7, myxoviruses, influenza A and B, respiratory syncytial virus, strain Long, and coronavirus strain 229E was studied in vitro, using different H2O2 concentration and timec of exposure. H2O2 in a 3 percent concentration inactivated all the viruses under study within 1--30 min. Coronavirus and influenza viruses were found to be most sensitive. Reoviruses, adenoviruses and adenoassociated virus were relatively stable. H2O2 is a convenient means for virus inactivation.", "contents": "[Virus inactivation by hydrogen peroxide]. The effect of H2O2 on adenovirus types 3 and 6, adenoassociated virus type 4, rhinoviruses 1A, 1B, and type 7, myxoviruses, influenza A and B, respiratory syncytial virus, strain Long, and coronavirus strain 229E was studied in vitro, using different H2O2 concentration and timec of exposure. H2O2 in a 3 percent concentration inactivated all the viruses under study within 1--30 min. Coronavirus and influenza viruses were found to be most sensitive. Reoviruses, adenoviruses and adenoassociated virus were relatively stable. H2O2 is a convenient means for virus inactivation."}
{"id": "PMID:203116", "title": "[Stimulation of mouse encephalomyocarditis virus reproduction by non-multiplying poliomyelitis virus in several transplantable tissue culture lines].", "content": "Reproduction of mouse encephalomyocarditis virus (EMC) was studied in 5 continuous primate cell lines: HeLa, Fl, Detroit-6, P/7, and MIO inoculated with guanidine-dependent variant of poliomyelitis virus in the absence of guanidine. Poliomyelitis virus stimulated EMC virus reproduction in all cell lines under study. This stimulation effect was studied at length in HeLa and MIO cells. In HeLa cells, stimulation was observed at a low and moderate multiplicity of infection of EMC virus but not at a high (100 PEU/cell) multiplicity. Also, when EMC virus reproduction was stimulated, a shortening of the latent period of its multiplication cycle, an increase in the number of antigen-containing cells and the number of infectious centers were observed. In MIO cells, stimulation was found to occur both with low and high doses of EMC virus but not to be accompanied by a shortening in the latent period of EMC reproduction cycle, or any increase in the antigen-containing cells or number of infectious centers. In both cell types upon mixed infection the synthesis of virus-specific RNA's of EMC virus was enhanced. It is suggested that the stimulating effect of poliomyelitis virus is realized in HeLa and MIO cells at different stages of EMC virus reproduction.", "contents": "[Stimulation of mouse encephalomyocarditis virus reproduction by non-multiplying poliomyelitis virus in several transplantable tissue culture lines]. Reproduction of mouse encephalomyocarditis virus (EMC) was studied in 5 continuous primate cell lines: HeLa, Fl, Detroit-6, P/7, and MIO inoculated with guanidine-dependent variant of poliomyelitis virus in the absence of guanidine. Poliomyelitis virus stimulated EMC virus reproduction in all cell lines under study. This stimulation effect was studied at length in HeLa and MIO cells. In HeLa cells, stimulation was observed at a low and moderate multiplicity of infection of EMC virus but not at a high (100 PEU/cell) multiplicity. Also, when EMC virus reproduction was stimulated, a shortening of the latent period of its multiplication cycle, an increase in the number of antigen-containing cells and the number of infectious centers were observed. In MIO cells, stimulation was found to occur both with low and high doses of EMC virus but not to be accompanied by a shortening in the latent period of EMC reproduction cycle, or any increase in the antigen-containing cells or number of infectious centers. In both cell types upon mixed infection the synthesis of virus-specific RNA's of EMC virus was enhanced. It is suggested that the stimulating effect of poliomyelitis virus is realized in HeLa and MIO cells at different stages of EMC virus reproduction."}
{"id": "PMID:203117", "title": "[Antiviral activity of several nucleic acid components methylated in the N-position].", "content": "The degree of reproducation of Rous sarcoma, mumps, and vaccinia viruses in chick embryo cell culture incubated in the presence of 9-methyladenine was considerably lower than reproducation of these viruses in the cells propagated without this substance. 1-methyluracil and 1-methylthymine reduced considerably the amount of Rous sarcoma virus produced by the cells as compared to the controls. The presence of these substances in the maintenance medium does not prevent virus infection of the cells, and their effect appears to be associated with nonspecific action on the late stages of the virus reproduction.", "contents": "[Antiviral activity of several nucleic acid components methylated in the N-position]. The degree of reproducation of Rous sarcoma, mumps, and vaccinia viruses in chick embryo cell culture incubated in the presence of 9-methyladenine was considerably lower than reproducation of these viruses in the cells propagated without this substance. 1-methyluracil and 1-methylthymine reduced considerably the amount of Rous sarcoma virus produced by the cells as compared to the controls. The presence of these substances in the maintenance medium does not prevent virus infection of the cells, and their effect appears to be associated with nonspecific action on the late stages of the virus reproduction."}
{"id": "PMID:203124", "title": "[The application of guanidine hydrochloride to the treatment of degenerative nervous and muscular diseases. I. Clinical results (author's transl)].", "content": "This paper reports the results obtained on using guanidine hydrochloride in the treatment of patients with amyotrophic lateral sclerosis, degenerative diseases of the spinocerebellar system or the peripheral nervous system and dystrophic muscle diseases. A long-term effect of the substance was a diminution in the rate of progression of the diseases, with the exception of the group with dystrophic muscle diseases. Initial clinical improvement occurred in certain patients of both groups. The substance seems to be more effective in less-advanced cases than on administration in the later stages of the disease. The therapeutic dosage was 20 to 40 mg/kg/day. The most frequent side-effect was paraesthesia and sometimes gastric disturbance was reported. Therapy had to be discontinued in 3 patients due to leucopenia. In these patients the symptoms rapidly increased in severity after discontinuation of treatment. This supports the assumption that guanidine hydrochloride treatment slows down the progress of the disease.", "contents": "[The application of guanidine hydrochloride to the treatment of degenerative nervous and muscular diseases. I. Clinical results (author's transl)]. This paper reports the results obtained on using guanidine hydrochloride in the treatment of patients with amyotrophic lateral sclerosis, degenerative diseases of the spinocerebellar system or the peripheral nervous system and dystrophic muscle diseases. A long-term effect of the substance was a diminution in the rate of progression of the diseases, with the exception of the group with dystrophic muscle diseases. Initial clinical improvement occurred in certain patients of both groups. The substance seems to be more effective in less-advanced cases than on administration in the later stages of the disease. The therapeutic dosage was 20 to 40 mg/kg/day. The most frequent side-effect was paraesthesia and sometimes gastric disturbance was reported. Therapy had to be discontinued in 3 patients due to leucopenia. In these patients the symptoms rapidly increased in severity after discontinuation of treatment. This supports the assumption that guanidine hydrochloride treatment slows down the progress of the disease."}
{"id": "PMID:203129", "title": "Dissimilatory nitrate reduction in Clostridium tertium.", "content": "Fermentation balance studies were carried out on Clostridium tertium grown with and without nitrate in the medium. Nitrate reduction increased the efficiency of energy produced from glucose by permitting the utilization of additional sites of substrate level phosphorylation. The effect was even more dramatic in C. tertium than in C. perfringens, with increased cell yields of about 30% being observed in the former compared with 20% in the latter. Unlike C. perfringens, C. tertium responded to the presence of nitrate in the medium with an increased growth rate. A slight increase in the Y ATP of these cultures was also observed, and quantitatively, this appeared to be consistent with the prediction of Stouthammer and Bettenhaussen that Y ATP will vary with the growth rate. Thus, C. tertium, like C. perfringens, was able to use nitrate as an electron acceptor in conjunction with its energy metabolism, suggesting that this may be widespread among the nitrate-reducing anaerobes.", "contents": "Dissimilatory nitrate reduction in Clostridium tertium. Fermentation balance studies were carried out on Clostridium tertium grown with and without nitrate in the medium. Nitrate reduction increased the efficiency of energy produced from glucose by permitting the utilization of additional sites of substrate level phosphorylation. The effect was even more dramatic in C. tertium than in C. perfringens, with increased cell yields of about 30% being observed in the former compared with 20% in the latter. Unlike C. perfringens, C. tertium responded to the presence of nitrate in the medium with an increased growth rate. A slight increase in the Y ATP of these cultures was also observed, and quantitatively, this appeared to be consistent with the prediction of Stouthammer and Bettenhaussen that Y ATP will vary with the growth rate. Thus, C. tertium, like C. perfringens, was able to use nitrate as an electron acceptor in conjunction with its energy metabolism, suggesting that this may be widespread among the nitrate-reducing anaerobes."}
{"id": "PMID:203133", "title": "[Dysostotic changes and the prognosis of Perthes' disease after operation (author's transl)].", "content": "Goff and Mau for the first time demonstrated dysostotic changes in children with Perthes' disease. Their effect on the course of the disease has not so far been determined. It was examined on 41 patients following varus-osteotomy. Follow-up after 2--6 years showed late radiologic results, measured against the total quotient (Heyman and Herndon) depended essentially on this dysostotic component. The worst results are seen in children with high-grade skeletal retardation. Final results are further influenced by age, stage of the disease at the time of surgery and pre-operative status. Age plays a part in that results are better the younger the child. There are obvious parallels between results of radiologic and histologic examination at the time of operation and the weightbearing capacity. Dysostotic changes prolong the course of Perthers's disease and cause long-term lack of firmness of the femoral head. The influence of these facts on the still controversial indication for surgery is discussed. Our findings suggest that protection against weightbearing should be prolonged after operation according to the dysostotic changes.", "contents": "[Dysostotic changes and the prognosis of Perthes' disease after operation (author's transl)]. Goff and Mau for the first time demonstrated dysostotic changes in children with Perthes' disease. Their effect on the course of the disease has not so far been determined. It was examined on 41 patients following varus-osteotomy. Follow-up after 2--6 years showed late radiologic results, measured against the total quotient (Heyman and Herndon) depended essentially on this dysostotic component. The worst results are seen in children with high-grade skeletal retardation. Final results are further influenced by age, stage of the disease at the time of surgery and pre-operative status. Age plays a part in that results are better the younger the child. There are obvious parallels between results of radiologic and histologic examination at the time of operation and the weightbearing capacity. Dysostotic changes prolong the course of Perthers's disease and cause long-term lack of firmness of the femoral head. The influence of these facts on the still controversial indication for surgery is discussed. Our findings suggest that protection against weightbearing should be prolonged after operation according to the dysostotic changes."}
{"id": "PMID:203128", "title": "Paraquat suicide in a young woman: results of therapy directed against the superoxide radical.", "content": "The clinical course of a young woman following two separate suicide attempts using the herbicide paraquat is reported. The patient survived an intramuscular injection of paraquat almost asymptomatically, but later exhibited a typical fatal course with fulminant proliferative pulmonary fibrosis after an intravenous injection. Fibrosis and death occurred despite a therapeutic regimen based upon a known action of paraquat, the generation of superoxide (O(2)[unk]), using superoxide dismutase, \u03b1-tocopherol, and ascorbic acid in conjunction with forced diuresis and prednisone. While treatment failed explanations for the failure of therapy in this case and current therapeutic alternatives are discussed so that they may be considered when future cases are encountered.", "contents": "Paraquat suicide in a young woman: results of therapy directed against the superoxide radical. The clinical course of a young woman following two separate suicide attempts using the herbicide paraquat is reported. The patient survived an intramuscular injection of paraquat almost asymptomatically, but later exhibited a typical fatal course with fulminant proliferative pulmonary fibrosis after an intravenous injection. Fibrosis and death occurred despite a therapeutic regimen based upon a known action of paraquat, the generation of superoxide (O(2)[unk]), using superoxide dismutase, \u03b1-tocopherol, and ascorbic acid in conjunction with forced diuresis and prednisone. While treatment failed explanations for the failure of therapy in this case and current therapeutic alternatives are discussed so that they may be considered when future cases are encountered."}
{"id": "PMID:203130", "title": "Characterization of a soluble NADH-independent nitrate reductase from the photosynthetic bacterium Rhodopseudomonas capsulata.", "content": "The assimilatory nitrate reductase was purified 60-fold from a newly isolated, nitrate assmilating strain of the photosynthetic bacterium Rhodopseudomonas capsulata. The enzyme had a molecular weight of about 180 000 dalton and was typically prokaryotic in that it was not active with reduced pyridine nucleotides but rather with reduced flavins.", "contents": "Characterization of a soluble NADH-independent nitrate reductase from the photosynthetic bacterium Rhodopseudomonas capsulata. The assimilatory nitrate reductase was purified 60-fold from a newly isolated, nitrate assmilating strain of the photosynthetic bacterium Rhodopseudomonas capsulata. The enzyme had a molecular weight of about 180 000 dalton and was typically prokaryotic in that it was not active with reduced pyridine nucleotides but rather with reduced flavins."}
{"id": "PMID:203132", "title": "Calcium gradient dependent pyrophosphate formation by sarcoplasmic vesicles.", "content": "The vesicles of the sarcoplasmic membranes synthesize pyrophosphate from inorganic phosphate. Pyrophosphate synthesis proceeds as long as a calcium gradient is maintained across the vesicular membranes. Pyrophosphate synthesis is inhibited by low concentrations of nucleoside triphosphates.", "contents": "Calcium gradient dependent pyrophosphate formation by sarcoplasmic vesicles. The vesicles of the sarcoplasmic membranes synthesize pyrophosphate from inorganic phosphate. Pyrophosphate synthesis proceeds as long as a calcium gradient is maintained across the vesicular membranes. Pyrophosphate synthesis is inhibited by low concentrations of nucleoside triphosphates."}
{"id": "PMID:203142", "title": "Enzymatic activity in a semi-gley soil under the floodplain forest in South Moravia.", "content": "In three profiles of a semi-gley soil under the floodplain forest, variations were studied in the activities of invertase, amylase, cellobiase, cellulase, proteases, and phosphatases. In the surface soil layer, enzymatic activity was found affected by the soil moisture at a significant level, whereas in the deeper soil layers the influence of aeration was more effective. Moreover, significant correlations could be detected between the amount of available nitrogen and protease activity, while the water-soluble phosphorus acted as a represeive agent on the activity of phosphatases. Existence of correlations between the numbers of microbes and enzymes could be demonstrated for invertase and protases only.", "contents": "Enzymatic activity in a semi-gley soil under the floodplain forest in South Moravia. In three profiles of a semi-gley soil under the floodplain forest, variations were studied in the activities of invertase, amylase, cellobiase, cellulase, proteases, and phosphatases. In the surface soil layer, enzymatic activity was found affected by the soil moisture at a significant level, whereas in the deeper soil layers the influence of aeration was more effective. Moreover, significant correlations could be detected between the amount of available nitrogen and protease activity, while the water-soluble phosphorus acted as a represeive agent on the activity of phosphatases. Existence of correlations between the numbers of microbes and enzymes could be demonstrated for invertase and protases only."}
{"id": "PMID:203143", "title": "[In vitro studies of the antiviral activity of ammonium humate against herpes simplex virus type 1 and type 2 (author's transl)].", "content": "Ammonium humate, isolated from peat water, is a higher molecular polyphenolic compound with a strong antiviral activity against herpes simplex virus type 1 and type 2. Three cell lines were chosen for examining the cytotoxicity of ammonium humate: rabbit kidney primary cells, HEp-2- and FL-cells. As the light microscopic examination of both, the monolayers and the stained cover-glass cultures, revealed, concentrations of up to 5 microgram/ml ammonium humate can be used without hesitation for rabbit kidney primary cells (Fig. 1, 2) 200 microgram/ml for HEp-2-cells (Fig. 3, 4, 5), and 2000 microgram/ml for FL-cells. Fresh prepared rabbit kidney primary cells and suspended FL-cells (Tab. 1) are most sensitive against ammonium humate than monolayers. A remarcable plaque inhibition effect on the multiplication of herpes simplex virus type 1 and type 2 has been observed in all cell systems at concentrations of 0.5-20 microgram/ml ammonium humate (Fig. 6). The inhibition of virus multiplication at concentrations of greater than 10 microgram/ml ammonium humate was independent of the incubation temperature (Fig. 8). The adsorption of the virus to the cell surface has been found to be the most humate-sensitive phase of the herpesvirus multiplication cycle (Fig. 7, 9, 10). A prophylactic effect in vitro could be observed at concentrations greater than 10 microgram/ml ammonium humate (Fig. 11, 12).", "contents": "[In vitro studies of the antiviral activity of ammonium humate against herpes simplex virus type 1 and type 2 (author's transl)]. Ammonium humate, isolated from peat water, is a higher molecular polyphenolic compound with a strong antiviral activity against herpes simplex virus type 1 and type 2. Three cell lines were chosen for examining the cytotoxicity of ammonium humate: rabbit kidney primary cells, HEp-2- and FL-cells. As the light microscopic examination of both, the monolayers and the stained cover-glass cultures, revealed, concentrations of up to 5 microgram/ml ammonium humate can be used without hesitation for rabbit kidney primary cells (Fig. 1, 2) 200 microgram/ml for HEp-2-cells (Fig. 3, 4, 5), and 2000 microgram/ml for FL-cells. Fresh prepared rabbit kidney primary cells and suspended FL-cells (Tab. 1) are most sensitive against ammonium humate than monolayers. A remarcable plaque inhibition effect on the multiplication of herpes simplex virus type 1 and type 2 has been observed in all cell systems at concentrations of 0.5-20 microgram/ml ammonium humate (Fig. 6). The inhibition of virus multiplication at concentrations of greater than 10 microgram/ml ammonium humate was independent of the incubation temperature (Fig. 8). The adsorption of the virus to the cell surface has been found to be the most humate-sensitive phase of the herpesvirus multiplication cycle (Fig. 7, 9, 10). A prophylactic effect in vitro could be observed at concentrations greater than 10 microgram/ml ammonium humate (Fig. 11, 12)."}
{"id": "PMID:203144", "title": "Media supplemented with nalidixic acid for the isolation of gram negative anaerobic bacteria.", "content": "The minimum inhibitory concentrations (MIC) of nalidixic acid were determined for thirty-four strains of Clostridium sp. by an agar dilution technique. The MIC range of Clostridium perfringens ran from 0.03 microgram/ml to 64 microgram/ml, according to a bimodal distribution. One half of the strains was inhibited by 0.25 microgram/ml. 64 microgram/ml was able to inhibit all the strains tested. The author suggests a systematic utilization of media with and without 40 microgram/ml nalidixic acid. These two media were parallely inoculated with clinical specimens where anaerobic bacteria were suspected, and allowed the isolation of gram negative anaerobes.", "contents": "Media supplemented with nalidixic acid for the isolation of gram negative anaerobic bacteria. The minimum inhibitory concentrations (MIC) of nalidixic acid were determined for thirty-four strains of Clostridium sp. by an agar dilution technique. The MIC range of Clostridium perfringens ran from 0.03 microgram/ml to 64 microgram/ml, according to a bimodal distribution. One half of the strains was inhibited by 0.25 microgram/ml. 64 microgram/ml was able to inhibit all the strains tested. The author suggests a systematic utilization of media with and without 40 microgram/ml nalidixic acid. These two media were parallely inoculated with clinical specimens where anaerobic bacteria were suspected, and allowed the isolation of gram negative anaerobes."}
{"id": "PMID:203147", "title": "[Fluorescent FAB-fragments of antibodies. Comparative assessment and utilization in immunofluorescent analysis].", "content": "The authors present the results of a comparative study of the immunofluorescent activity and the specificity of fluorescent Fab-fragments of antibodies to R. prowazeki, D. sibericus, and B. pertussis obtained by the enzymatic hydrolysis of specific immunoglobulins with papain. Fluorescent Fab-fragments of antibodies possessed the same sensitivity and specificity as the homologous fluorescent antibodies, but had an advantage of a much weaker capacity to nonspecific fluorescence and a relatively higher staining properties. Fluorescent Fab-fragments of antibodies, in contrast to the fluorescent antibodies of the same specificity, permitted to detect the antibody searched in the concentrated crude material, and thus increased the possibilities of the immunofluorescent analysis.", "contents": "[Fluorescent FAB-fragments of antibodies. Comparative assessment and utilization in immunofluorescent analysis]. The authors present the results of a comparative study of the immunofluorescent activity and the specificity of fluorescent Fab-fragments of antibodies to R. prowazeki, D. sibericus, and B. pertussis obtained by the enzymatic hydrolysis of specific immunoglobulins with papain. Fluorescent Fab-fragments of antibodies possessed the same sensitivity and specificity as the homologous fluorescent antibodies, but had an advantage of a much weaker capacity to nonspecific fluorescence and a relatively higher staining properties. Fluorescent Fab-fragments of antibodies, in contrast to the fluorescent antibodies of the same specificity, permitted to detect the antibody searched in the concentrated crude material, and thus increased the possibilities of the immunofluorescent analysis."}
{"id": "PMID:203148", "title": "[Characteristics of paradoxical sleep in different types of epileptic seizures].", "content": "In 136 patients with different forms of epileptic strokes paradoxal sleep (PS) was studied. Shifts of a qualitative and quantitative character were revealed. The latter, in particular was expressed in a dissociative type of PS when muscular tension was preserved. The found changes were expressed more severely in patients with polymorphic and psychomotor strokes in the frontotemporal and frontal localization of the epileptic focus. In general, the same patients registered paroxysmal and epileptic activity in the period of PS, what was infrequently found in other forms of epileptic strokes, however, it had never coincided with the registration of rapid ocular movements. The role of PS physiological mechanisms in suppression of epileptic activity and possible ways of searching for more effective antiepileptic measures are discussed.", "contents": "[Characteristics of paradoxical sleep in different types of epileptic seizures]. In 136 patients with different forms of epileptic strokes paradoxal sleep (PS) was studied. Shifts of a qualitative and quantitative character were revealed. The latter, in particular was expressed in a dissociative type of PS when muscular tension was preserved. The found changes were expressed more severely in patients with polymorphic and psychomotor strokes in the frontotemporal and frontal localization of the epileptic focus. In general, the same patients registered paroxysmal and epileptic activity in the period of PS, what was infrequently found in other forms of epileptic strokes, however, it had never coincided with the registration of rapid ocular movements. The role of PS physiological mechanisms in suppression of epileptic activity and possible ways of searching for more effective antiepileptic measures are discussed."}
{"id": "PMID:203149", "title": "[Connections between spinal ganglia in the pathogenesis of reflex-distant pain syndromes].", "content": "Using the complex of the neurohistological research methods the author studied spinal ganglia, spinal cord (37 dogs) following the removal of groups of the spinal ganglia in the cervical and thoracic sections. Widely spread distant receptor-reflex systems of the connections between spinal ganglia accompanied by dendrites and axones were revealed. The fibres of these systems pass in the Bechterew intermediate regions of the posterior columns of the spinal cord. The straight interneuronal connections between the cervical and lumbar spinal ganglia were found. On the basis of the obtained data the author conducted analysis of the mechanism of the occurrence of reflex-distant pain syndromes in patients with ganglio-radiculoneuralgia in degenerative diseases of the vertebral column. The reflex-distant syndrome occurs due to irritation of spinal ganglion neurons accomplishing distant ganglion connections.", "contents": "[Connections between spinal ganglia in the pathogenesis of reflex-distant pain syndromes]. Using the complex of the neurohistological research methods the author studied spinal ganglia, spinal cord (37 dogs) following the removal of groups of the spinal ganglia in the cervical and thoracic sections. Widely spread distant receptor-reflex systems of the connections between spinal ganglia accompanied by dendrites and axones were revealed. The fibres of these systems pass in the Bechterew intermediate regions of the posterior columns of the spinal cord. The straight interneuronal connections between the cervical and lumbar spinal ganglia were found. On the basis of the obtained data the author conducted analysis of the mechanism of the occurrence of reflex-distant pain syndromes in patients with ganglio-radiculoneuralgia in degenerative diseases of the vertebral column. The reflex-distant syndrome occurs due to irritation of spinal ganglion neurons accomplishing distant ganglion connections."}
{"id": "PMID:203150", "title": "Comparative activation by AMP and cyclic-AMP of rat erythrocyte and reticulocyte glycolysis.", "content": "Incubation of raty erythrocytes and reticulocytes in Tris-Ringer's medium with 5 mM cyclic-AMP or AMP increased lactate formation and glucose utilization. The glycolysis-stimulating effect of cyclic-AMP is very similar to that of AMP and, in both cases, it seems to be higher in reticulocytes than in erythrocytes. 0.5 mM norepinephrine produced a much higher lactate formation in reticulocytes than in erythrocytes, suggesting a greater adenylate cyclase activity in younger cells. 300 micrometer cyclic-AMP and AMP reverse inhibition produced by ATP (up to 1.5 micrometer) on phosphofructokinase from rat reticulocyte haemolysates. Both nucleotides are positive allosteric effectors of the enzyme as shown by displacement of F6P-saturation curve to hyperbolic kinetics. Similar results were previously obtained with rat erythrocytes. This deinhibitory effect is suggested to be responsible of the above glycolysis-stimulating effect.", "contents": "Comparative activation by AMP and cyclic-AMP of rat erythrocyte and reticulocyte glycolysis. Incubation of raty erythrocytes and reticulocytes in Tris-Ringer's medium with 5 mM cyclic-AMP or AMP increased lactate formation and glucose utilization. The glycolysis-stimulating effect of cyclic-AMP is very similar to that of AMP and, in both cases, it seems to be higher in reticulocytes than in erythrocytes. 0.5 mM norepinephrine produced a much higher lactate formation in reticulocytes than in erythrocytes, suggesting a greater adenylate cyclase activity in younger cells. 300 micrometer cyclic-AMP and AMP reverse inhibition produced by ATP (up to 1.5 micrometer) on phosphofructokinase from rat reticulocyte haemolysates. Both nucleotides are positive allosteric effectors of the enzyme as shown by displacement of F6P-saturation curve to hyperbolic kinetics. Similar results were previously obtained with rat erythrocytes. This deinhibitory effect is suggested to be responsible of the above glycolysis-stimulating effect."}
{"id": "PMID:203151", "title": "Carbon balance studies with various substrates in human erythrocytes.", "content": "Carbon metabolism in erythrocytes has been found to be in balance with a variety of substrates studied. The contribution of the 2,3-bisphosphoglycerate pathway to carbon metabolism depends on the rates of carbon utilization and increases with increasing metabolic rates. Net decrease of the 2,3-bisphosphoglycerate level acts as a NAD regenerating system thus facilitating uptake of polyalcohols such as xylitol.", "contents": "Carbon balance studies with various substrates in human erythrocytes. Carbon metabolism in erythrocytes has been found to be in balance with a variety of substrates studied. The contribution of the 2,3-bisphosphoglycerate pathway to carbon metabolism depends on the rates of carbon utilization and increases with increasing metabolic rates. Net decrease of the 2,3-bisphosphoglycerate level acts as a NAD regenerating system thus facilitating uptake of polyalcohols such as xylitol."}
{"id": "PMID:203153", "title": "Superoxide anion and drug-induced hemolysis.", "content": "Superoxide anion, either generated during the autooxidation of dihydroxyfumaria acid or by the interaction of 1,4-naphthoquinone-2-sulfonate and intracellular hemoglobin in red cells pretreated with the intracellular superoxide dismutase inhibitor, diethyldithiocarbamate, produces structural changes in red cells hemoglobin and hypotonic lysis. No evidence for lipid peroxidation was found in red cells exposed to either 1,4 naphthoquinone-2-sulfonate in the presence of diethyldithiocarbamate or to dihydroxyfumaric acid, although the membranes of these cells exposed to either 1,4 naphthoquinone-2-sulfonate in the presence of diethyldithiocarbamate or to dihydroxyfumaric acid, although the membranes of these cells retained a green pigment. These results suggest that superoxide anion reacts with cellular hemoglobin to form hemoglobin breakdown products which bind to the red cell membrane and thereby increase the osmotic fragility of the cell.", "contents": "Superoxide anion and drug-induced hemolysis. Superoxide anion, either generated during the autooxidation of dihydroxyfumaria acid or by the interaction of 1,4-naphthoquinone-2-sulfonate and intracellular hemoglobin in red cells pretreated with the intracellular superoxide dismutase inhibitor, diethyldithiocarbamate, produces structural changes in red cells hemoglobin and hypotonic lysis. No evidence for lipid peroxidation was found in red cells exposed to either 1,4 naphthoquinone-2-sulfonate in the presence of diethyldithiocarbamate or to dihydroxyfumaric acid, although the membranes of these cells exposed to either 1,4 naphthoquinone-2-sulfonate in the presence of diethyldithiocarbamate or to dihydroxyfumaric acid, although the membranes of these cells retained a green pigment. These results suggest that superoxide anion reacts with cellular hemoglobin to form hemoglobin breakdown products which bind to the red cell membrane and thereby increase the osmotic fragility of the cell."}
{"id": "PMID:203156", "title": "Electron spin resonance spectra of chicken liver and hepatoma tissue embedded in paraffin.", "content": "ESR spectra of chicken liver and hepatoma tissue embedded in paraffin display signals characteristic of free radicals and paramagnetic complexes. Owing to embedding the spectrum is altered as compared to that of the native tissue but remains characteristic of the respective tissues. The spectra of tissues embedded in paraffin allow no more than qualitative conclusions to be drawn concerning the spectra of the native tissues, even if appropriate controls are applied.", "contents": "Electron spin resonance spectra of chicken liver and hepatoma tissue embedded in paraffin. ESR spectra of chicken liver and hepatoma tissue embedded in paraffin display signals characteristic of free radicals and paramagnetic complexes. Owing to embedding the spectrum is altered as compared to that of the native tissue but remains characteristic of the respective tissues. The spectra of tissues embedded in paraffin allow no more than qualitative conclusions to be drawn concerning the spectra of the native tissues, even if appropriate controls are applied."}
{"id": "PMID:203158", "title": "X-ray microanalytical studies of lead-implanted rat brains.", "content": "Various cytoplasmic and intranuclear inclusions found in macrophages and astrocytes of lead-implanted rat brains were studied with an energy dispersive x-ray microanalytical technique. Cytoplasmic inclusions contained large quantities of lead, calcium and phosphorus. The proportions of these elements were different within each inclusion. Intranuclear inclusions also contained small amounts of lead and, occasionally, calcium.", "contents": "X-ray microanalytical studies of lead-implanted rat brains. Various cytoplasmic and intranuclear inclusions found in macrophages and astrocytes of lead-implanted rat brains were studied with an energy dispersive x-ray microanalytical technique. Cytoplasmic inclusions contained large quantities of lead, calcium and phosphorus. The proportions of these elements were different within each inclusion. Intranuclear inclusions also contained small amounts of lead and, occasionally, calcium."}
{"id": "PMID:203159", "title": "Glial cell characteristics in bulk-prepared cell fractions from human brain tumours.", "content": "The heterogeneity of brain tumours, especially in the glioblastoma group, makes biochemical characterization of pieces of the tumours hazardous even with extensive histological controls. This study employs a technique by which separate cell populations are subsequently isolated from the tumours by means of density gradient centrifugation. Cells isolated from glial brain tumours with low density sedimentation rates show the highest levels of glial cell characteristics, i.e. S-100 content and active uptake of the neurotransmitter GABA.", "contents": "Glial cell characteristics in bulk-prepared cell fractions from human brain tumours. The heterogeneity of brain tumours, especially in the glioblastoma group, makes biochemical characterization of pieces of the tumours hazardous even with extensive histological controls. This study employs a technique by which separate cell populations are subsequently isolated from the tumours by means of density gradient centrifugation. Cells isolated from glial brain tumours with low density sedimentation rates show the highest levels of glial cell characteristics, i.e. S-100 content and active uptake of the neurotransmitter GABA."}
{"id": "PMID:203160", "title": "Subependymoma: a case report with ultrastructural study.", "content": "A case history illustrating the potential clinical significance of subependymoma is presented. Fine structural studies indicate that the tumor is composed of cells having the cytoplasmic features of ependyma, astrocytes, and transitional cells. Its composition and structure are alike those in the adult mammalian subependymal layer.", "contents": "Subependymoma: a case report with ultrastructural study. A case history illustrating the potential clinical significance of subependymoma is presented. Fine structural studies indicate that the tumor is composed of cells having the cytoplasmic features of ependyma, astrocytes, and transitional cells. Its composition and structure are alike those in the adult mammalian subependymal layer."}
{"id": "PMID:203161", "title": "Nasopharyngeal cancer in Greenland. The incidence in an Arctic Eskimo population.", "content": "Nasopharyngeal cancer is very common among the Chinese in various parts of the world, particularly Southern China, and frequent in certain other Mongoloid groups in Southeast Asia. Also, the incidence among the Eskimos of the western Canadian Arctic and Alaska is considerably higher than would be expected. Ths paper reports for the first time the incidence of nasopharyngeal cancer among native Greenlanders, an Eskimo population with some admixture of Caucasian blood. During 1955-1976, thirty-five cases of nasopharyngeal cancer were diagnosed. Ninety-four per cent (33 cases) were squamous cell carcinomas, including lymphoepitheliomas. Incidence rates 1965-1976, age adjusted to the \"world\" population distribution, were 12.3 and 8.5 per 100,000 per annum for males and females respectively. These rates are among the highest recorded in the world and significantly higher than among the Caucasian population in Denmark. Compared with other high risk populations nasopharyngeal cancer among Greenlanders had an older age distribution and a lower male-to-female sex ratio. An additional 11 cases with malignant involvement, seeminly confined only to cervical lymph nodes, may have included some undiagnosed nasopharyngeal cancers. Thus the calculated incidence rates of this study could represent only minimum rates. Further research is needed especially with regard to the HL-A profile and to possible traces of Epstein-Barr virus infection.", "contents": "Nasopharyngeal cancer in Greenland. The incidence in an Arctic Eskimo population. Nasopharyngeal cancer is very common among the Chinese in various parts of the world, particularly Southern China, and frequent in certain other Mongoloid groups in Southeast Asia. Also, the incidence among the Eskimos of the western Canadian Arctic and Alaska is considerably higher than would be expected. Ths paper reports for the first time the incidence of nasopharyngeal cancer among native Greenlanders, an Eskimo population with some admixture of Caucasian blood. During 1955-1976, thirty-five cases of nasopharyngeal cancer were diagnosed. Ninety-four per cent (33 cases) were squamous cell carcinomas, including lymphoepitheliomas. Incidence rates 1965-1976, age adjusted to the \"world\" population distribution, were 12.3 and 8.5 per 100,000 per annum for males and females respectively. These rates are among the highest recorded in the world and significantly higher than among the Caucasian population in Denmark. Compared with other high risk populations nasopharyngeal cancer among Greenlanders had an older age distribution and a lower male-to-female sex ratio. An additional 11 cases with malignant involvement, seeminly confined only to cervical lymph nodes, may have included some undiagnosed nasopharyngeal cancers. Thus the calculated incidence rates of this study could represent only minimum rates. Further research is needed especially with regard to the HL-A profile and to possible traces of Epstein-Barr virus infection."}
{"id": "PMID:203162", "title": "Induction of latent Herpes simplex virus type 2 infection in human cervical epithelial cells in vitro.", "content": "An in vitro method was used to induce non-productive herpes simplex virus type 2 (HSV-2) infections in human ecto- and endocervical epithelial cells. Adenine arabinoside (ara-A) could prevent the replication of HSV-2 in ecto- and endocervical cells and after removal of ara-A from growth medium a rapid destruction of explants with development of infectious virus was observed. When ara-A was not withdrawn until 4 days or later after in vitro infection the morphological, immunofluorescent and virological studies detected no infections. However, 2-3 weeks after inoculation there were in some cultures morphological as well as immunofluorescent signs of HSV infection without demonstrable infectious virus, indicating an incidental abortive nature of the infective process.", "contents": "Induction of latent Herpes simplex virus type 2 infection in human cervical epithelial cells in vitro. An in vitro method was used to induce non-productive herpes simplex virus type 2 (HSV-2) infections in human ecto- and endocervical epithelial cells. Adenine arabinoside (ara-A) could prevent the replication of HSV-2 in ecto- and endocervical cells and after removal of ara-A from growth medium a rapid destruction of explants with development of infectious virus was observed. When ara-A was not withdrawn until 4 days or later after in vitro infection the morphological, immunofluorescent and virological studies detected no infections. However, 2-3 weeks after inoculation there were in some cultures morphological as well as immunofluorescent signs of HSV infection without demonstrable infectious virus, indicating an incidental abortive nature of the infective process."}
{"id": "PMID:203163", "title": "Quantitative immunoelectrophoretic studies of the L and S antigens of vaccinia virus.", "content": "The L (10S) and S (7S) antigens of vaccinia virus have been characterized by their sensitivity to heat, to proteolytic enzymes and to periodate. The L antigen was heat labile and inactivated by proteolytic enzymes and periodate. Treatment with trypsin for 1 min indicated that the S antigen was built up of at least two protein subunits of about 3S and 5S. One of the subunits was highly sensitive to heat and to proteolytic enzymes. On further treatment with trypsin the other subunit was split in two components showing partial identity serologically.", "contents": "Quantitative immunoelectrophoretic studies of the L and S antigens of vaccinia virus. The L (10S) and S (7S) antigens of vaccinia virus have been characterized by their sensitivity to heat, to proteolytic enzymes and to periodate. The L antigen was heat labile and inactivated by proteolytic enzymes and periodate. Treatment with trypsin for 1 min indicated that the S antigen was built up of at least two protein subunits of about 3S and 5S. One of the subunits was highly sensitive to heat and to proteolytic enzymes. On further treatment with trypsin the other subunit was split in two components showing partial identity serologically."}
{"id": "PMID:203164", "title": "Inhibition of noradrenaline-stimulated lipolysis and cyclic AMP accumulation in isolated rat adipocytes by purified phospholipase C and theta-toxin from Clostridium perfringens.", "content": "Purified phospholipae C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) and theta-toxin from Clostridium perfringens both inhibited noradrenaline-stimulated lipolysis and cyclic AMP accumulation in isolated rat adipocytes in a dose-dependent manner. The action of phospholipase C was gradual in onset, while the effect of theta-toxin was almost immediate. Phospholipase C, but not theta-toxin, hydrolyzed membrane phospholipids and inhibited adenylate cyclase (EC 4.6.1.1) in a crude membrane fraction from fat cells. The inhibitory effects of phospholipase C were associated with morphological alterations detectable by electron microscopy, whereas effects of theta-toxin were observed at a time when no clearcut morphological alterations could be observed. It is concluded that the two purified principles from C. perfringens, which are both present in commercial preparations of phospholipase C, antagonize noradrenaline-stimulated cyclic AMP accumulation and lipolysis. Although their exact mechanisms of action have not been elucidated, phospholipase C and theta-toxin have different modes of attack.", "contents": "Inhibition of noradrenaline-stimulated lipolysis and cyclic AMP accumulation in isolated rat adipocytes by purified phospholipase C and theta-toxin from Clostridium perfringens. Purified phospholipae C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) and theta-toxin from Clostridium perfringens both inhibited noradrenaline-stimulated lipolysis and cyclic AMP accumulation in isolated rat adipocytes in a dose-dependent manner. The action of phospholipase C was gradual in onset, while the effect of theta-toxin was almost immediate. Phospholipase C, but not theta-toxin, hydrolyzed membrane phospholipids and inhibited adenylate cyclase (EC 4.6.1.1) in a crude membrane fraction from fat cells. The inhibitory effects of phospholipase C were associated with morphological alterations detectable by electron microscopy, whereas effects of theta-toxin were observed at a time when no clearcut morphological alterations could be observed. It is concluded that the two purified principles from C. perfringens, which are both present in commercial preparations of phospholipase C, antagonize noradrenaline-stimulated cyclic AMP accumulation and lipolysis. Although their exact mechanisms of action have not been elucidated, phospholipase C and theta-toxin have different modes of attack."}
{"id": "PMID:203165", "title": "Cellular action of gastrointestinal polypeptide hormones.", "content": "The present state of chemistry, structure-activity relationship and cellular mode of action of gastrointestinal polypeptide hormones (gastrin, secretin, cholecystokinin-pancreozymin, caerulein and bombesin) are reviewed. Possible structure of polypeptide receptors and the mechanism of peptide--receptor interaction are described, and the role of acetylcholine and histamine in secretion discussed. The present data support the hormonal-receptor significance of cyclic nucleotides (cAMP, cGMP) in the cellular regulation of secretion.", "contents": "Cellular action of gastrointestinal polypeptide hormones. The present state of chemistry, structure-activity relationship and cellular mode of action of gastrointestinal polypeptide hormones (gastrin, secretin, cholecystokinin-pancreozymin, caerulein and bombesin) are reviewed. Possible structure of polypeptide receptors and the mechanism of peptide--receptor interaction are described, and the role of acetylcholine and histamine in secretion discussed. The present data support the hormonal-receptor significance of cyclic nucleotides (cAMP, cGMP) in the cellular regulation of secretion."}
{"id": "PMID:203166", "title": "Effect of ACTH1-24 and ACTH4-10 on distribution of 3H-noradrenaline in the brain of adrenalectomized rats.", "content": "Painful stimuli led to a decrease of the radioactive catecholamine pool in adrenalectomized rats. Intraventricular administration of both tritiated noradrenaline and ACTH produced a greater decrease of the labelled catecholamine pool than in the control adrenalectomized rats in 12 to 18 hr following injection. Blocking of monoamino-oxidase activity or biosynthesis by systemic administration of Pargyline or alpha-methyl-tyrosine did not prevent the effect of ACTH on brain catecholamines. It is concluded that ACTH exerts a direct influence on the brain catecholaminergic system and that this effect might be involved in ACTH dependent behavioural responses.", "contents": "Effect of ACTH1-24 and ACTH4-10 on distribution of 3H-noradrenaline in the brain of adrenalectomized rats. Painful stimuli led to a decrease of the radioactive catecholamine pool in adrenalectomized rats. Intraventricular administration of both tritiated noradrenaline and ACTH produced a greater decrease of the labelled catecholamine pool than in the control adrenalectomized rats in 12 to 18 hr following injection. Blocking of monoamino-oxidase activity or biosynthesis by systemic administration of Pargyline or alpha-methyl-tyrosine did not prevent the effect of ACTH on brain catecholamines. It is concluded that ACTH exerts a direct influence on the brain catecholaminergic system and that this effect might be involved in ACTH dependent behavioural responses."}
{"id": "PMID:203167", "title": "The phases of sleep and wakefulness after bilateral labyrinth destruction in chronic cats.", "content": "After bilateral destruction of the labyrinths, the duration of paradoxical sleep increased from 4% in the intact animals to 8% after destruction. This increase was the result of an increase from 2.2 to 2.6 in the average number of epiodes of paradoxical sleep as well as of an increase from 3.2 to 5.5 min of the duration of each episode of paradoxical sleep. One latency of the first appearance of an episode was shortened, from the 77th min at the beginning of registration to the 43rd min after destruction. During this time the duration of wakefulness decreased from 30% to 17%.", "contents": "The phases of sleep and wakefulness after bilateral labyrinth destruction in chronic cats. After bilateral destruction of the labyrinths, the duration of paradoxical sleep increased from 4% in the intact animals to 8% after destruction. This increase was the result of an increase from 2.2 to 2.6 in the average number of epiodes of paradoxical sleep as well as of an increase from 3.2 to 5.5 min of the duration of each episode of paradoxical sleep. One latency of the first appearance of an episode was shortened, from the 77th min at the beginning of registration to the 43rd min after destruction. During this time the duration of wakefulness decreased from 30% to 17%."}
{"id": "PMID:203169", "title": "Pertussis vaccine--fact and fiction.", "content": "The present paper indicates a number of unresolved problems in the metabolism of Bordetella pertussis and in the standardization of pertussis vaccines. The use of chemically defined media should enable the metabolic problems to be clarified. The problems concerned with the control and standardization of vaccines can largely be resolved in the laboratory with the introduction of reference preparations but the question of the reactivity of vaccine remains for the future.", "contents": "Pertussis vaccine--fact and fiction. The present paper indicates a number of unresolved problems in the metabolism of Bordetella pertussis and in the standardization of pertussis vaccines. The use of chemically defined media should enable the metabolic problems to be clarified. The problems concerned with the control and standardization of vaccines can largely be resolved in the laboratory with the introduction of reference preparations but the question of the reactivity of vaccine remains for the future."}
{"id": "PMID:203170", "title": "Significance of the surface of crystalline silicogenic dusts in experimental silicosis.", "content": "Crystalline, silicogenic quartz dusts possess a marked basic dye-binding capacity even in strong acid media (pH 1.0), which points to negative surface charges of the dusts. Presumably this surface property of the dusts may be related to their silicogenic effect. This hypothesis has been tested by pretreatment of the dusts with basic dyes for binding the negative surface charges. The dusts were administered intratracheally to rats. The results obtained after 8 and 12 months revealed that staining by basic dyes of the dusts decreases their silicogenic activity.", "contents": "Significance of the surface of crystalline silicogenic dusts in experimental silicosis. Crystalline, silicogenic quartz dusts possess a marked basic dye-binding capacity even in strong acid media (pH 1.0), which points to negative surface charges of the dusts. Presumably this surface property of the dusts may be related to their silicogenic effect. This hypothesis has been tested by pretreatment of the dusts with basic dyes for binding the negative surface charges. The dusts were administered intratracheally to rats. The results obtained after 8 and 12 months revealed that staining by basic dyes of the dusts decreases their silicogenic activity."}
{"id": "PMID:203171", "title": "Special forms of initial gastric cancer.", "content": "1. Fifty-five microscopic cancer foci from 11 gastric resection preparations have been examined. Each focus than 5 mm was less in diameter. They occurred mostly in regions showing chronic atrophic gastritis, less frequently in the margin of peptic ulcer or in a polyp located in the antrum along the lesser curve. The lesions were discovered at routine histologic examination of stomachs operated upon for other primary diseases. 2. Histologically differentiated and undifferentiated types could be distinguished. They were: well differentiated adenocarcinoma, tubular adenocarcinoma, \"intraluminal papillary proliferation of the glandular neck\", \"glandular neck displasia\" mucocellular and muconodular carcinoma, and carcinoma in situ. In some cases, different histologic types within the same focus, or more foci of diverse structure in the same patient could be observed. 3. A malignant process developing from the glandular neck region or the surface epithelium could be demonstrated in each type of initial cancer.", "contents": "Special forms of initial gastric cancer. 1. Fifty-five microscopic cancer foci from 11 gastric resection preparations have been examined. Each focus than 5 mm was less in diameter. They occurred mostly in regions showing chronic atrophic gastritis, less frequently in the margin of peptic ulcer or in a polyp located in the antrum along the lesser curve. The lesions were discovered at routine histologic examination of stomachs operated upon for other primary diseases. 2. Histologically differentiated and undifferentiated types could be distinguished. They were: well differentiated adenocarcinoma, tubular adenocarcinoma, \"intraluminal papillary proliferation of the glandular neck\", \"glandular neck displasia\" mucocellular and muconodular carcinoma, and carcinoma in situ. In some cases, different histologic types within the same focus, or more foci of diverse structure in the same patient could be observed. 3. A malignant process developing from the glandular neck region or the surface epithelium could be demonstrated in each type of initial cancer."}
{"id": "PMID:203172", "title": "Cerebral pseudocysts following chemotherapy of glioblastomas.", "content": "Three cases of pseudocysts following surgery and chemotherapy for glioblastomas are reported. Their clinical picture was similar, consisting of intracranial hypertension without primary modification of focal signs. CT scanning has been able to detect the cystic aspect and to eliminate a true tumour recurrence. Medical treatment (steroids or Mannitol) seems inefficient. Evacuation of the cyst is the only efficient method of treatment.", "contents": "Cerebral pseudocysts following chemotherapy of glioblastomas. Three cases of pseudocysts following surgery and chemotherapy for glioblastomas are reported. Their clinical picture was similar, consisting of intracranial hypertension without primary modification of focal signs. CT scanning has been able to detect the cystic aspect and to eliminate a true tumour recurrence. Medical treatment (steroids or Mannitol) seems inefficient. Evacuation of the cyst is the only efficient method of treatment."}
{"id": "PMID:203174", "title": "The contribution of tryptophan to the regulation of the NAD+ level in mouse liver.", "content": "It has been observed that the NAD level is lower in regenerating and growing mouse liver than in resting liver of adult mice. Also it has been found that in proliferating liver the NAD biosynthesis from nicotinamide and nicotinate is unchanged whereas that from tryptophan is reduced. Under these conditions the enzymatic activity of the kynureninase is decreased and the activity of the kynurenine aminotransferase as well as of the tryptophan pyrrolase is not altered. From these and other data of the literature it is concluded that the NAD biosynthesis from tryptophan is important for the regulation of the hepatic NAD level, through this pathway and the NAD degradation nicotinamide is formed which is transported to the non-hepatic tissues to act as a NAD precursor there. The possible interrelation between the NAD metabolism and the DNA synthesis is discussed.", "contents": "The contribution of tryptophan to the regulation of the NAD+ level in mouse liver. It has been observed that the NAD level is lower in regenerating and growing mouse liver than in resting liver of adult mice. Also it has been found that in proliferating liver the NAD biosynthesis from nicotinamide and nicotinate is unchanged whereas that from tryptophan is reduced. Under these conditions the enzymatic activity of the kynureninase is decreased and the activity of the kynurenine aminotransferase as well as of the tryptophan pyrrolase is not altered. From these and other data of the literature it is concluded that the NAD biosynthesis from tryptophan is important for the regulation of the hepatic NAD level, through this pathway and the NAD degradation nicotinamide is formed which is transported to the non-hepatic tissues to act as a NAD precursor there. The possible interrelation between the NAD metabolism and the DNA synthesis is discussed."}
{"id": "PMID:203176", "title": "Myocardial scintigraphy with technetrium-99m pyrophosphate during the early phase of acute infarction.", "content": "To determine the sensitivity of myocardial scintigraphy with technetium-99m pyrophosphate during the early phase of acute myocardial infarction, 31 patients admitted to the coronary care unit with prolonged ischemic pain underwent imaging within 4 to 8 hours and again at 24 hours after the onset of symptoms. In 11 of 15 patients with documented acute myocardial infarction, increased focal myocardial uptake was demonstrated on early myocardial scintigraphy. Focal uptake was observed in only 2 of 16 patients with unstable angina pectoris. Three or four patients with normal early scintigrams had massive transmural myocardial infarction. Normal early scintigrams in these three patients may have reflected poor perfusion because the images were abnormal at 24 hours. In four patients the extent of technetium-99m pyrophosphate uptake increased more than 20 percent at 24 hours without other evidence of infarct extension. In the other seven patients, there was no significant change in the area of the abnormal radioactive uptake between early and delayed scintiscans. This study suggests that technetium-99m pyrophosphate scintigraphy can defect acute myocardial infarction as early as 4 hours after the onset of symptoms although the sensitivity rate (73 percent) is less than that at 24 hours.", "contents": "Myocardial scintigraphy with technetrium-99m pyrophosphate during the early phase of acute infarction. To determine the sensitivity of myocardial scintigraphy with technetium-99m pyrophosphate during the early phase of acute myocardial infarction, 31 patients admitted to the coronary care unit with prolonged ischemic pain underwent imaging within 4 to 8 hours and again at 24 hours after the onset of symptoms. In 11 of 15 patients with documented acute myocardial infarction, increased focal myocardial uptake was demonstrated on early myocardial scintigraphy. Focal uptake was observed in only 2 of 16 patients with unstable angina pectoris. Three or four patients with normal early scintigrams had massive transmural myocardial infarction. Normal early scintigrams in these three patients may have reflected poor perfusion because the images were abnormal at 24 hours. In four patients the extent of technetium-99m pyrophosphate uptake increased more than 20 percent at 24 hours without other evidence of infarct extension. In the other seven patients, there was no significant change in the area of the abnormal radioactive uptake between early and delayed scintiscans. This study suggests that technetium-99m pyrophosphate scintigraphy can defect acute myocardial infarction as early as 4 hours after the onset of symptoms although the sensitivity rate (73 percent) is less than that at 24 hours."}
{"id": "PMID:203180", "title": "Alpha1-antitrypsin, protein marker in oral contraceptive-associated hepatic tumors.", "content": "Tissue specimens from a series of 46 hepatic tumors occurring in young female oral contraceptive users were tested for alpha1-antitrypsin deposition, utilizing immunocytochemical and histochemical methods. In two instances serum alpha1-antitrypsin phenotyping was also performed. Immunoreactive alpha1-antitrypsin deposits were demonstrated in benign lesions, including 56% of cases of focal nodular hyperplasia and 68% of cases of liver-cell adenoma, and in 89% of cases of malignant hepatoma. There was good correlation between alpha1-antitrypsin deposits and variable amounts of finely granular, or globular, diastase-resistant periodic acid-Schiff positivity within tumor cells. While quantitative differences in alpha1-antitrypsin deposits between benign and malignant cell proliferations were not observed, a qualitative continuum that linked all tumors in the study group was found. The findings suggest that alpha1-antitrypsin deficiency is not related to the hepatic tumors developing in oral contraceptive users. The tumor tissue deposits of alpha1-antitrypsin observed represent a marker protein, the significance of which is undefined.", "contents": "Alpha1-antitrypsin, protein marker in oral contraceptive-associated hepatic tumors. Tissue specimens from a series of 46 hepatic tumors occurring in young female oral contraceptive users were tested for alpha1-antitrypsin deposition, utilizing immunocytochemical and histochemical methods. In two instances serum alpha1-antitrypsin phenotyping was also performed. Immunoreactive alpha1-antitrypsin deposits were demonstrated in benign lesions, including 56% of cases of focal nodular hyperplasia and 68% of cases of liver-cell adenoma, and in 89% of cases of malignant hepatoma. There was good correlation between alpha1-antitrypsin deposits and variable amounts of finely granular, or globular, diastase-resistant periodic acid-Schiff positivity within tumor cells. While quantitative differences in alpha1-antitrypsin deposits between benign and malignant cell proliferations were not observed, a qualitative continuum that linked all tumors in the study group was found. The findings suggest that alpha1-antitrypsin deficiency is not related to the hepatic tumors developing in oral contraceptive users. The tumor tissue deposits of alpha1-antitrypsin observed represent a marker protein, the significance of which is undefined."}
{"id": "PMID:203181", "title": "Intraleukocytic spore formation and leukocytic vacuolization during Clostridium perfringens septicemia.", "content": "The case of a patient with fulminant Clostridium perfringens septicemia and intravascular hemolysis is presented. The organisms in the blood stream were in sufficient quantity to be detected on a peripheral blood smear, and some were found to be within leukocytes. In vivo spore formation by C. perfringens is thought to be uncommon; however, in this patient probable spore formation by this organism was observed within peripheral blood leukocytes. The peripheral polymorphonuclear leukocytes from this patient were also markedly vacuolated.", "contents": "Intraleukocytic spore formation and leukocytic vacuolization during Clostridium perfringens septicemia. The case of a patient with fulminant Clostridium perfringens septicemia and intravascular hemolysis is presented. The organisms in the blood stream were in sufficient quantity to be detected on a peripheral blood smear, and some were found to be within leukocytes. In vivo spore formation by C. perfringens is thought to be uncommon; however, in this patient probable spore formation by this organism was observed within peripheral blood leukocytes. The peripheral polymorphonuclear leukocytes from this patient were also markedly vacuolated."}
{"id": "PMID:203182", "title": "Isolation of cytomegalovirus from cerebrospinal fluid of a congenitally infected infant.", "content": "The isolation of cytomegalovirus (CMV) from the CSF of an infant with congenital disease is documented. Samples of urine sediments and CSF were inoculated into tissue cultures of human foreskin fibroblast cells. Cytopathology was evident within 48 hours in those tubes inoculated with CSF. The urine cultures were later positive. All viral isolates were identified by complement fixation tests using known positive CMV antiserum.", "contents": "Isolation of cytomegalovirus from cerebrospinal fluid of a congenitally infected infant. The isolation of cytomegalovirus (CMV) from the CSF of an infant with congenital disease is documented. Samples of urine sediments and CSF were inoculated into tissue cultures of human foreskin fibroblast cells. Cytopathology was evident within 48 hours in those tubes inoculated with CSF. The urine cultures were later positive. All viral isolates were identified by complement fixation tests using known positive CMV antiserum."}
{"id": "PMID:203183", "title": "Granular cell myoblastoma: a cause of biliary obstruction.", "content": "An 11-year-old boy was seen with gradual onset of jaundice. Dilated bile ducts were demonstrated by ultrasound and computerized axial tomography. The obstruction was caused by an unusual benign tumor, a granular cell myoblastoma. Cure was effected by resection and choledochojejunostomy.", "contents": "Granular cell myoblastoma: a cause of biliary obstruction. An 11-year-old boy was seen with gradual onset of jaundice. Dilated bile ducts were demonstrated by ultrasound and computerized axial tomography. The obstruction was caused by an unusual benign tumor, a granular cell myoblastoma. Cure was effected by resection and choledochojejunostomy."}
{"id": "PMID:203184", "title": "Infectious mononucleosis and the Epstein-Barr virus.", "content": "Recent elucidation of the relationship between the Epstein-Barr virus and infectious mononucleosis has resulted in the development of new diagnostic serological tests, and has amplified our knowledge of the epidemiological and clinical aspects of the disease. The history, epidemiology, clinical characteristics, diagnostic features, and therapy of infectious mononucleosis are reviewed. This is done in the light of recent knowledge concerning the Epstein-Barr virus as well as previous studies employing the traditional diagnostic criteria of heterophil positivity, the classical clinical symdromes, and characteristic changes in the blood cell count. Immunological studies concerning host resistance and its occasional failure are reviewed with particular reference to T and B lymphocyte activity in the disease.", "contents": "Infectious mononucleosis and the Epstein-Barr virus. Recent elucidation of the relationship between the Epstein-Barr virus and infectious mononucleosis has resulted in the development of new diagnostic serological tests, and has amplified our knowledge of the epidemiological and clinical aspects of the disease. The history, epidemiology, clinical characteristics, diagnostic features, and therapy of infectious mononucleosis are reviewed. This is done in the light of recent knowledge concerning the Epstein-Barr virus as well as previous studies employing the traditional diagnostic criteria of heterophil positivity, the classical clinical symdromes, and characteristic changes in the blood cell count. Immunological studies concerning host resistance and its occasional failure are reviewed with particular reference to T and B lymphocyte activity in the disease."}
{"id": "PMID:203185", "title": "Metiamide: more than an H2-receptor antagonist.", "content": "The effect of metiamide on acid secretion and calcium uptake by the frog gastric mucosa was tested alone and in combination with histamine, pentagastrin, aminophylline, and dibutyrl cyclic AMP (db cAMP). Metiamide inhibited all stimulants including db cAMP which presumably acts intracellularly beyond the H2 receptor. Metiamide, therefore, actively inhibits at a point within the cell beyond the adenylated cyclase membrane receptor complexes. Metiamide also increases calcium influx into the parietal cell, suggesting yet another possible mechanism of inhibition.", "contents": "Metiamide: more than an H2-receptor antagonist. The effect of metiamide on acid secretion and calcium uptake by the frog gastric mucosa was tested alone and in combination with histamine, pentagastrin, aminophylline, and dibutyrl cyclic AMP (db cAMP). Metiamide inhibited all stimulants including db cAMP which presumably acts intracellularly beyond the H2 receptor. Metiamide, therefore, actively inhibits at a point within the cell beyond the adenylated cyclase membrane receptor complexes. Metiamide also increases calcium influx into the parietal cell, suggesting yet another possible mechanism of inhibition."}
{"id": "PMID:203186", "title": "Prevalence of antibody to hepatitis A and polioviruses in an unimmunized urban population.", "content": "A large group of sera collected in 1954-1955 from people living in the metropolitan area of Melbourne, Australia, was tested for neutralizing antibody to polioviruses 1,2 and 3 and for antibody to hepatitis A virus by solid phase radioimmunoassay. The age-specific prevalence of antibody to each virus was remarkable similar, being highest in the elderly and in persons of low socioeconomic status. Antibody to each virus was acquired early in life, with more than half the population showing evidence of infection by the age of 15 years.", "contents": "Prevalence of antibody to hepatitis A and polioviruses in an unimmunized urban population. A large group of sera collected in 1954-1955 from people living in the metropolitan area of Melbourne, Australia, was tested for neutralizing antibody to polioviruses 1,2 and 3 and for antibody to hepatitis A virus by solid phase radioimmunoassay. The age-specific prevalence of antibody to each virus was remarkable similar, being highest in the elderly and in persons of low socioeconomic status. Antibody to each virus was acquired early in life, with more than half the population showing evidence of infection by the age of 15 years."}
{"id": "PMID:203187", "title": "Tonsillectomy and infectious mononucleosis.", "content": "Tonsillar tissue may be the primary site of infection with Epstein-Barr virus (EBV), the etiologic agent of classical infectious mononucleosis (IM). Therefore, a retrospective study of the association between tonsillectomy and IM was performed in a college student population. In the first part of the study, tonsillectomy rates were compared between 164 IM-positive students and 164 student controls who attended UCLA in 1972-1975. Although it was determined that the development of IM during college years was statistically less commin in tonsillectomized students, the difference was not inordinately large and probably had no significant biologic meaning. The authors speculate that the difference was due to the greater likelihood, and greater yield, in considering the diagnosis of IM in young adults with enlarged, inflamed tonsils. In support of this is the fact that IM-positive students who had received a prior tonsillectomy usually had the surgical procedure performed at a younger age than the control group. Conceivably, tonsillar ablation in the very young is more liable to result in incomplete removal and eventual regrowth of this tissue. Indeed, six IM-positive students who had received a tonsillectomy at six years of age or less were found to have exudate in tonsillar fossae or pillars during their IM episode. In the second part of the study, clinical and laboratory measures were found to be similar between a larger group of IM-positive students with or without a history of prior tonsillectomy.", "contents": "Tonsillectomy and infectious mononucleosis. Tonsillar tissue may be the primary site of infection with Epstein-Barr virus (EBV), the etiologic agent of classical infectious mononucleosis (IM). Therefore, a retrospective study of the association between tonsillectomy and IM was performed in a college student population. In the first part of the study, tonsillectomy rates were compared between 164 IM-positive students and 164 student controls who attended UCLA in 1972-1975. Although it was determined that the development of IM during college years was statistically less commin in tonsillectomized students, the difference was not inordinately large and probably had no significant biologic meaning. The authors speculate that the difference was due to the greater likelihood, and greater yield, in considering the diagnosis of IM in young adults with enlarged, inflamed tonsils. In support of this is the fact that IM-positive students who had received a prior tonsillectomy usually had the surgical procedure performed at a younger age than the control group. Conceivably, tonsillar ablation in the very young is more liable to result in incomplete removal and eventual regrowth of this tissue. Indeed, six IM-positive students who had received a tonsillectomy at six years of age or less were found to have exudate in tonsillar fossae or pillars during their IM episode. In the second part of the study, clinical and laboratory measures were found to be similar between a larger group of IM-positive students with or without a history of prior tonsillectomy."}
{"id": "PMID:203188", "title": "Acute gastroenteritis among schoolchildren associated with reovirus-like agent.", "content": "During early summer 1975 and spring 1976, outbreaks of acute gastroenteritis were reported from primary schools and other institutions in several districts of Japan. Outbreaks occurred in an explosive manner resembling mass food poisoning from a school lunch. The majority of patients were in the age group 6-14 years. Clinical features were generally mild, consisting of vomiting and/or diarrhea, often with low-grade fever. Reovirus-like agents in the feces were found in 27 (44%) of 62 patients. The virus found in feces of schoolchildren with acute gastroenteritis (SCGV) was related morphologically as well as serologically, not only to the agent found in infantile gastroenteritis (IGV), but also to neonatal calf diarrhea virus (NCDV). A slight difference in antigenicity between SCGV and IGV as suggested by cross complement fixation (CF) remains to be elucidated. About one-half of paired sera from 54 patients showed a significant rise in CF antibody against SCGV and/or NCDV. The pattern of neutralizing (NT) antibody against NCDV in patients' sera was similar to that of CF antibody. Most children studied had a titer of 1:4 or greater of CF and/or NT antibodies to SCGV and NCDV in acute sera. The relationship between acute gastroenteritis associated with reovirus-like agent in infants and that in schoolchildren is discussed.", "contents": "Acute gastroenteritis among schoolchildren associated with reovirus-like agent. During early summer 1975 and spring 1976, outbreaks of acute gastroenteritis were reported from primary schools and other institutions in several districts of Japan. Outbreaks occurred in an explosive manner resembling mass food poisoning from a school lunch. The majority of patients were in the age group 6-14 years. Clinical features were generally mild, consisting of vomiting and/or diarrhea, often with low-grade fever. Reovirus-like agents in the feces were found in 27 (44%) of 62 patients. The virus found in feces of schoolchildren with acute gastroenteritis (SCGV) was related morphologically as well as serologically, not only to the agent found in infantile gastroenteritis (IGV), but also to neonatal calf diarrhea virus (NCDV). A slight difference in antigenicity between SCGV and IGV as suggested by cross complement fixation (CF) remains to be elucidated. About one-half of paired sera from 54 patients showed a significant rise in CF antibody against SCGV and/or NCDV. The pattern of neutralizing (NT) antibody against NCDV in patients' sera was similar to that of CF antibody. Most children studied had a titer of 1:4 or greater of CF and/or NT antibodies to SCGV and NCDV in acute sera. The relationship between acute gastroenteritis associated with reovirus-like agent in infants and that in schoolchildren is discussed."}
{"id": "PMID:203189", "title": "Isozyme patterns in erythrocytes from human fetuses.", "content": "Starch gel electrophoretic patterns of 26 enzymes (corresponding to 36 gene loci) were examined in hemolysates of erythrocytes from 11 first-trimester and mid-trimester human fetuses (65-138 gestation days). The zymograms of 16 enzymes were identical in fetal and control adult red cells. Six enzymes (enolase, guanylate kinase, lactate dehydrogenase, nucleoside phosphorylase, phosphofructokinase, hexokinase) showed differences in the staining intensity of certain isozyme zones as compared with the controls. Also, the fetal red cell zymograms, in contrast to those of adults, contained the mitochondrial forms of isocitric dehydrogenase and glutamic oxaloacetic transaminase as well as more definite zones of phosphoglucomutase-3. Finally, some of the isozymes of uridine diphosphate kinase in the fetal cells had slightly retarded mobility. These observed differences between fetal and adult red cells could reflect the expression of a different program of protein synthesis in red cells of the fetuses or the epigenetic modifications of isozymes in immature red cells.", "contents": "Isozyme patterns in erythrocytes from human fetuses. Starch gel electrophoretic patterns of 26 enzymes (corresponding to 36 gene loci) were examined in hemolysates of erythrocytes from 11 first-trimester and mid-trimester human fetuses (65-138 gestation days). The zymograms of 16 enzymes were identical in fetal and control adult red cells. Six enzymes (enolase, guanylate kinase, lactate dehydrogenase, nucleoside phosphorylase, phosphofructokinase, hexokinase) showed differences in the staining intensity of certain isozyme zones as compared with the controls. Also, the fetal red cell zymograms, in contrast to those of adults, contained the mitochondrial forms of isocitric dehydrogenase and glutamic oxaloacetic transaminase as well as more definite zones of phosphoglucomutase-3. Finally, some of the isozymes of uridine diphosphate kinase in the fetal cells had slightly retarded mobility. These observed differences between fetal and adult red cells could reflect the expression of a different program of protein synthesis in red cells of the fetuses or the epigenetic modifications of isozymes in immature red cells."}
{"id": "PMID:203190", "title": "Liver disease in renal transplant recipients.", "content": "Liver disease is a common complication in renal transplant recipients. Several types of liver disease can occur. The most common are acute and chronic hepatitis. The variety of acute hepatitis include hepatitis A, hepatitis B, cytomegalovirus hepatitis, herpes simplex hepatitis and azathioprine hepatitis. The incidence of azathioprine hepatitis may not be as high as initially suggested. Chronic hepatitis is a serious problem because the disease seems to be progressive despite prednisone therapy. The causes of this chronic hepatitis are not fully known, although hepatitis B, cytomegalovirus and herpes simplex virus have been implicated. Discontinuation of azathioprine therapy has no appreciable effect on the course of chronic hepatitis.", "contents": "Liver disease in renal transplant recipients. Liver disease is a common complication in renal transplant recipients. Several types of liver disease can occur. The most common are acute and chronic hepatitis. The variety of acute hepatitis include hepatitis A, hepatitis B, cytomegalovirus hepatitis, herpes simplex hepatitis and azathioprine hepatitis. The incidence of azathioprine hepatitis may not be as high as initially suggested. Chronic hepatitis is a serious problem because the disease seems to be progressive despite prednisone therapy. The causes of this chronic hepatitis are not fully known, although hepatitis B, cytomegalovirus and herpes simplex virus have been implicated. Discontinuation of azathioprine therapy has no appreciable effect on the course of chronic hepatitis."}
{"id": "PMID:203192", "title": "Effects of intravenous isoxsuprine and ritodrine, with and without concomitant dexamethasone, on fetoplacental and pituitary hormones and cyclic adenosine monophosphate during late pregnancy.", "content": "Beta sympathomimetic drugs are used to inhibit preterm labor and glucocorticoids to accelerate fetal pulmonary maturation. A study was designed to investigate the hormonal effects of intravenous infusion of isoxsuprine 150 to 200 mcg. per minute or ritodrine 100 to 150 mcg. per minute in a series of 28 women at 28 to 40 weeks' gestation, with and without concomitant dexamethasone therapy. Serial serum samples taken before and during the six hours of infusion were assayed for cyclic adenosine-3,5-monophosphate (AMP), estradiol, estriol, progesterone, human placental lactogen (hPL), thyrotropin (TSH), follicle-stimulating hormone (FSH), and human growth hormone (gGH). Ritodrine was more potent than isoxsuprine in increasing the circulating levels of cyclic AMP. The levels of placental steroid hormones decreased slightly, as did the ratio of progesterone to estradiol. Human placental lactogen and pituitary hormones showed no consistent changes. Simultaneous administration of dexamethasone did not modify these results.", "contents": "Effects of intravenous isoxsuprine and ritodrine, with and without concomitant dexamethasone, on fetoplacental and pituitary hormones and cyclic adenosine monophosphate during late pregnancy. Beta sympathomimetic drugs are used to inhibit preterm labor and glucocorticoids to accelerate fetal pulmonary maturation. A study was designed to investigate the hormonal effects of intravenous infusion of isoxsuprine 150 to 200 mcg. per minute or ritodrine 100 to 150 mcg. per minute in a series of 28 women at 28 to 40 weeks' gestation, with and without concomitant dexamethasone therapy. Serial serum samples taken before and during the six hours of infusion were assayed for cyclic adenosine-3,5-monophosphate (AMP), estradiol, estriol, progesterone, human placental lactogen (hPL), thyrotropin (TSH), follicle-stimulating hormone (FSH), and human growth hormone (gGH). Ritodrine was more potent than isoxsuprine in increasing the circulating levels of cyclic AMP. The levels of placental steroid hormones decreased slightly, as did the ratio of progesterone to estradiol. Human placental lactogen and pituitary hormones showed no consistent changes. Simultaneous administration of dexamethasone did not modify these results."}
{"id": "PMID:203193", "title": "The histogenesis of hepatoma occurring spontaneously in a strain of sand rats (Psammomys obesus).", "content": "Spontaneous hepatomas and hepatic preneoplastic changes were observed in sand rats (Psammomys obesus) from two colonies. Both colonies originated from 10 sand rats captured in the Judean desert in 1969. At the age of 6 months, and increasing in multiplicity with advancing age, histologic examination revealed nodules containing hepatocytes characterized by hyperbasophilia, accumulation of glycogen, eosinophilic cytoplasm, or a mixture of these cells. In animals over 25 months old hepatocellular carcinoma was diagnosed. The histologic changes described here were reported to be characteristic of chemical hepatomagenesis in rats. No external chemical carcinogen could be demonstrated in our animal colonies, and a hereditary predisposition to tumor formation is presumed. Identity of hepatic carcinogenesis, irrespective of etiology in distantly related rodents, ie, the laboratory rat and the sand rat, which in reality is a gerbil, supports the assumption of the existence of a general law governing hepatic carcinogenesis.", "contents": "The histogenesis of hepatoma occurring spontaneously in a strain of sand rats (Psammomys obesus). Spontaneous hepatomas and hepatic preneoplastic changes were observed in sand rats (Psammomys obesus) from two colonies. Both colonies originated from 10 sand rats captured in the Judean desert in 1969. At the age of 6 months, and increasing in multiplicity with advancing age, histologic examination revealed nodules containing hepatocytes characterized by hyperbasophilia, accumulation of glycogen, eosinophilic cytoplasm, or a mixture of these cells. In animals over 25 months old hepatocellular carcinoma was diagnosed. The histologic changes described here were reported to be characteristic of chemical hepatomagenesis in rats. No external chemical carcinogen could be demonstrated in our animal colonies, and a hereditary predisposition to tumor formation is presumed. Identity of hepatic carcinogenesis, irrespective of etiology in distantly related rodents, ie, the laboratory rat and the sand rat, which in reality is a gerbil, supports the assumption of the existence of a general law governing hepatic carcinogenesis."}
{"id": "PMID:203194", "title": "Increased calcium uptake by muscle mitochondria of cold-acclimated rats.", "content": "Skeletal muscle mitochondria of cold-acclimated rats have an altered morphology that is related to the occurrence of nonshivering thermogenesis. The transport of calcium by these mitochondria was studied in a search for an alteration in an energy-dissipating mechanism which might be related to the altered morphology and to the altered mode of thermogenesis in the cold-acclimated animal. The rates of calcium uptake, of calcium-stimulated respiration, and of state 4 respiration after calcium uptake were increased in the altered mitochondria. The capacity to accumulate calcium without phosphate was increased, whereas with phosphate all the calcium was removed from the medium and no difference in total uptake was seen. Spontaneous release of calcium was greater but sodium-induced release was unchanged. No effect of cyclic AMP or prostaglandin E1 on release of calcium was seen. The increase in rate of calcium uptake occurred gradually during the first 3-5 wk of acclimation to cold. The results are considered to give some support to the hypothesis that adaptive changes in the mitochondrial calcium transport cycle in skeletal muscle occur during acclimation to cold.", "contents": "Increased calcium uptake by muscle mitochondria of cold-acclimated rats. Skeletal muscle mitochondria of cold-acclimated rats have an altered morphology that is related to the occurrence of nonshivering thermogenesis. The transport of calcium by these mitochondria was studied in a search for an alteration in an energy-dissipating mechanism which might be related to the altered morphology and to the altered mode of thermogenesis in the cold-acclimated animal. The rates of calcium uptake, of calcium-stimulated respiration, and of state 4 respiration after calcium uptake were increased in the altered mitochondria. The capacity to accumulate calcium without phosphate was increased, whereas with phosphate all the calcium was removed from the medium and no difference in total uptake was seen. Spontaneous release of calcium was greater but sodium-induced release was unchanged. No effect of cyclic AMP or prostaglandin E1 on release of calcium was seen. The increase in rate of calcium uptake occurred gradually during the first 3-5 wk of acclimation to cold. The results are considered to give some support to the hypothesis that adaptive changes in the mitochondrial calcium transport cycle in skeletal muscle occur during acclimation to cold."}
{"id": "PMID:203196", "title": "Inhibition of drinking in water-deprived rats by combined central angiotensin II and cholinergic receptor blockade.", "content": "The effect of blockade of central angiotensin II (AII) receptors and cholinergic receptors on thirst induced by water deprivation was studied in Sprague-Dawley rats and rats with hereditary hypothalamic diabetes insipidus (DI). Neither central AII nor cholinergic blockade alone affected drinking. Antagonism of both receptors simultaneously, however, significantly inhibited water intake of both Sprague-Dawley and DI rats. This inhibitory effect was not observed in water-deprived, nephrectomized rats. The combined antagonism on water intake was specific, since milk intake in hungry rats was not affected by simultaneous AII and cholinergic blockade. Isorenin concentrations in brain tissue were at control levels in water-deprived, nephrectomized, and non-nephrectomized Sprague-Dawley rats but were increased in water-deprived DI rats. The results suggest that angiotensin and cholinergic receptors in the brain have a physiological role in thirst. Thirst is maintained when either receptor is intact, but reduced when both receptors are inhibited by antagonists. They are independently capable of maintaining thirst.", "contents": "Inhibition of drinking in water-deprived rats by combined central angiotensin II and cholinergic receptor blockade. The effect of blockade of central angiotensin II (AII) receptors and cholinergic receptors on thirst induced by water deprivation was studied in Sprague-Dawley rats and rats with hereditary hypothalamic diabetes insipidus (DI). Neither central AII nor cholinergic blockade alone affected drinking. Antagonism of both receptors simultaneously, however, significantly inhibited water intake of both Sprague-Dawley and DI rats. This inhibitory effect was not observed in water-deprived, nephrectomized rats. The combined antagonism on water intake was specific, since milk intake in hungry rats was not affected by simultaneous AII and cholinergic blockade. Isorenin concentrations in brain tissue were at control levels in water-deprived, nephrectomized, and non-nephrectomized Sprague-Dawley rats but were increased in water-deprived DI rats. The results suggest that angiotensin and cholinergic receptors in the brain have a physiological role in thirst. Thirst is maintained when either receptor is intact, but reduced when both receptors are inhibited by antagonists. They are independently capable of maintaining thirst."}
{"id": "PMID:203197", "title": "Fast, rate-sensitive corticosteroid negative feedback during stress.", "content": "Characteristics of the fast, rate-sensitive, negative-feedback regulation of adrenocorticotropin secretion during stress was quantitatively analyzed using rats anesthetized with pentobarbital sodium. Various levels of plasma corticosterone were achieved during morning hours by infusing corticosterone solutions of different concentrations. Blood was sampled serially from the carotid artery. An increase in plasma corticosterone concentration 15 min after intravenous, pulsed injection of histamine (230 microgram) during saline intravenous infusion was defined as the \"control response\". When plasma corticosterone was rising during corticosterone infusion, the response to histamine stimulus was distinctly inhibited (fast, rate-sensitive feedback inhibition), whereas such an inhibition was not observed when plasma corticosterone levels were not rising, regardless of the absolute level. The critical rate of rise of plasma corticosterone, at or above which the fast rate-sensitive feedback was manifested, was 4-6 microgram/100 ml per min. When three graded doses of histamine were injected while plasma corticosterone levels were increasing at a rate of 6 microgram/100 ml per min, the absolute value of the inhibition observed was independent of the administered dose of the stressor. A hypothetical model for the mechanism of this feedback inhibition, based on the assumption that the hormone effect was proportional to the rate of formation of hormone-receptor complex, satisfied the quantitative characteristics of the inhibition experimentally observed in this study.", "contents": "Fast, rate-sensitive corticosteroid negative feedback during stress. Characteristics of the fast, rate-sensitive, negative-feedback regulation of adrenocorticotropin secretion during stress was quantitatively analyzed using rats anesthetized with pentobarbital sodium. Various levels of plasma corticosterone were achieved during morning hours by infusing corticosterone solutions of different concentrations. Blood was sampled serially from the carotid artery. An increase in plasma corticosterone concentration 15 min after intravenous, pulsed injection of histamine (230 microgram) during saline intravenous infusion was defined as the \"control response\". When plasma corticosterone was rising during corticosterone infusion, the response to histamine stimulus was distinctly inhibited (fast, rate-sensitive feedback inhibition), whereas such an inhibition was not observed when plasma corticosterone levels were not rising, regardless of the absolute level. The critical rate of rise of plasma corticosterone, at or above which the fast rate-sensitive feedback was manifested, was 4-6 microgram/100 ml per min. When three graded doses of histamine were injected while plasma corticosterone levels were increasing at a rate of 6 microgram/100 ml per min, the absolute value of the inhibition observed was independent of the administered dose of the stressor. A hypothetical model for the mechanism of this feedback inhibition, based on the assumption that the hormone effect was proportional to the rate of formation of hormone-receptor complex, satisfied the quantitative characteristics of the inhibition experimentally observed in this study."}
{"id": "PMID:203199", "title": "Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion.", "content": "The effects of intravenous infusion of Asp1. Ile5-angiotensin II on blood pressure, plasma vasopressin, ACTH and 11-hydroxycorticosteroid levels and on plasma renin activity were studied in five trained, conscious dogs. The dogs were prepared with bilateral carotid loops. Infusion of angiotensin II at rates of 5, 10, and 20 ng/kg.min raised its plasma concentration from 23 +/- 7 to 48 +/- 8, 125 +/- 8, and 187 +/- 21 pg/ml, respectively. The lowest rate of infusion was mildly pressor, the two higher rates more so. All rates of infusion promptly increased vasopressin levels and depressed renin levels. The two higher rates also stimulated ACTH, although with a latency of 30-45 min. Since the rates of infusion of angiotensin II employed produced plasma levels within the physiological range, it is suggested that peripherally generated angiotensin II may play an important role in the regulation of vasopressin, and ACTH secretion.", "contents": "Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion. The effects of intravenous infusion of Asp1. Ile5-angiotensin II on blood pressure, plasma vasopressin, ACTH and 11-hydroxycorticosteroid levels and on plasma renin activity were studied in five trained, conscious dogs. The dogs were prepared with bilateral carotid loops. Infusion of angiotensin II at rates of 5, 10, and 20 ng/kg.min raised its plasma concentration from 23 +/- 7 to 48 +/- 8, 125 +/- 8, and 187 +/- 21 pg/ml, respectively. The lowest rate of infusion was mildly pressor, the two higher rates more so. All rates of infusion promptly increased vasopressin levels and depressed renin levels. The two higher rates also stimulated ACTH, although with a latency of 30-45 min. Since the rates of infusion of angiotensin II employed produced plasma levels within the physiological range, it is suggested that peripherally generated angiotensin II may play an important role in the regulation of vasopressin, and ACTH secretion."}
{"id": "PMID:203201", "title": "A clinicopathologic study of steroid-related liver tumors.", "content": "A registry of liver tumors was started in late 1973 in an attempt to assess the relationship of these tumors to oral contraceptives or to other environmental factors. This report is concerned with the pathological aspects and the possible pathogenesis of the first 101 tumors accessioned. There were 44 instances of focal nodular hyperplasia, 40 adenomas, four unclassified but probably benign tumors, and 13 hepatocellular carcinomas. Eighty-one patients took oral contraceptives; six were associated with pregnancy; three had taken estrogens for long periods of time; one had a thecoma; four never took sex steroids; and in five the history was unknown. Tumor rupture and intrahepatic hemorrhage were frequent complications. It is possible that the vascular lesions associated with focal nodular hyperplasia could play a part in their pathogenesis as well as with rupture. Foci of adenomatous hyperplasia may be related to the development of adenomas. The association of these tumors with sex steroids could be coincidental. The fact that none of the patients had cirrhosis of liver fibrosis, and that androgenic anabolic steroid therapy has been associated with hepatocellular carcinomas in males, suggests that further study of the problem is necessary.", "contents": "A clinicopathologic study of steroid-related liver tumors. A registry of liver tumors was started in late 1973 in an attempt to assess the relationship of these tumors to oral contraceptives or to other environmental factors. This report is concerned with the pathological aspects and the possible pathogenesis of the first 101 tumors accessioned. There were 44 instances of focal nodular hyperplasia, 40 adenomas, four unclassified but probably benign tumors, and 13 hepatocellular carcinomas. Eighty-one patients took oral contraceptives; six were associated with pregnancy; three had taken estrogens for long periods of time; one had a thecoma; four never took sex steroids; and in five the history was unknown. Tumor rupture and intrahepatic hemorrhage were frequent complications. It is possible that the vascular lesions associated with focal nodular hyperplasia could play a part in their pathogenesis as well as with rupture. Foci of adenomatous hyperplasia may be related to the development of adenomas. The association of these tumors with sex steroids could be coincidental. The fact that none of the patients had cirrhosis of liver fibrosis, and that androgenic anabolic steroid therapy has been associated with hepatocellular carcinomas in males, suggests that further study of the problem is necessary."}
{"id": "PMID:203202", "title": "Osteosarcoma of bone and its important recognizable varieties.", "content": "Osteosarcoma of bone is a recognizable entity if the histopathologist designates tumors as such when their malignatn cells produce osteoid substance even if only in small foci. Such definition distinguishes this lesion from other sarcomas that arise in bone, especially chondrosarcoma and fibrosarcoma. There is a general tendency to consider that osteosarcomas represent a stereotyped form of disease for which new modalities of treatment can be applied and assessed. The question of whether a given osseous lesion is actually malignant and not a benign neoplasm or even a reactive non-neoplastic condition simulating a malignant tumor may be difficult for the histopathologist. Pathologists without considerable experience in the diagnosis of bone tumors find this question especially vexing. The establishment of a valid diagnosis of osteosarcoma introduces the additional problem that the 11 varieties considered in this paper may pose significant recognizable variations in the clinical capability of the disease. It is apparent that the physician must recognize the known clinicopathologic and prognostic factors of these subtypes in his assessment of the overall problem.", "contents": "Osteosarcoma of bone and its important recognizable varieties. Osteosarcoma of bone is a recognizable entity if the histopathologist designates tumors as such when their malignatn cells produce osteoid substance even if only in small foci. Such definition distinguishes this lesion from other sarcomas that arise in bone, especially chondrosarcoma and fibrosarcoma. There is a general tendency to consider that osteosarcomas represent a stereotyped form of disease for which new modalities of treatment can be applied and assessed. The question of whether a given osseous lesion is actually malignant and not a benign neoplasm or even a reactive non-neoplastic condition simulating a malignant tumor may be difficult for the histopathologist. Pathologists without considerable experience in the diagnosis of bone tumors find this question especially vexing. The establishment of a valid diagnosis of osteosarcoma introduces the additional problem that the 11 varieties considered in this paper may pose significant recognizable variations in the clinical capability of the disease. It is apparent that the physician must recognize the known clinicopathologic and prognostic factors of these subtypes in his assessment of the overall problem."}
{"id": "PMID:203204", "title": "Pulmonary alveolar cell carcinoma. Fine structural and in vitro study of a case and critical review of this entity.", "content": "Alveolar cell carcinoma is an unusual pulmonary neoplasm composed of cells with the ultrastructural features of granular pneumocytes. In the past this lesion has been grouped with peripheral well-differentiated mucin-secreting adenocarcinomas under the heading of bronchiolo-alveolar cell carcinoma. Because the existence of alveolar cell carcinoma as a distinct entity has been disputed, we examined a case ultrastructurally and confirmed that the neoplastic cells exhibit granular pneumocyte differentiation (lamellar bodies and abundant surface microvilli). In addition, we have growth this tumor in organ culture for up to 5 months and have documented the persistence of granular pneumocyte differentiation during this period. The accumulated evidence from human and animal studies that the granular pneumocyte may undergo neoplastic transformation is briefly reviewed. We conclude that alveolar cell carcinoma is a distinct entity; however, the elucidation of its natural history must await series that separate this lesion from other pulmonary carcinomas.", "contents": "Pulmonary alveolar cell carcinoma. Fine structural and in vitro study of a case and critical review of this entity. Alveolar cell carcinoma is an unusual pulmonary neoplasm composed of cells with the ultrastructural features of granular pneumocytes. In the past this lesion has been grouped with peripheral well-differentiated mucin-secreting adenocarcinomas under the heading of bronchiolo-alveolar cell carcinoma. Because the existence of alveolar cell carcinoma as a distinct entity has been disputed, we examined a case ultrastructurally and confirmed that the neoplastic cells exhibit granular pneumocyte differentiation (lamellar bodies and abundant surface microvilli). In addition, we have growth this tumor in organ culture for up to 5 months and have documented the persistence of granular pneumocyte differentiation during this period. The accumulated evidence from human and animal studies that the granular pneumocyte may undergo neoplastic transformation is briefly reviewed. We conclude that alveolar cell carcinoma is a distinct entity; however, the elucidation of its natural history must await series that separate this lesion from other pulmonary carcinomas."}
{"id": "PMID:203212", "title": "[The determination of age and sex from measure of the humerus (author's transl)].", "content": "On a total of seventy left humeri of persons in their third to ninth decades of life thirty different bone dimensions were determined macroscoically and checked for age dependence. Strong dependence on age was shown only by the weight and volume of the humerus as well as by the areal and thickness dimensins of the center of the shaft. These were used to set up multidimensional linear regression functions by which it is possible for the age of persons past thirty to be estimated with defined accuracy. Also calculated were discriminant functions which allow the sex of a person to be identified to be determined from three dimensions of the left humeral head, and these are the size of the caput at the cartilage-to-bone interface, the transverse and vertical diameters of the caput humeri or head of the humerus. Of the 49 cases studied only three were found to be in the region of overlap of the dimensions used for calculation. Consequently, the formula would not allow unknown humeri or skeletons, respectively, to be identified as belonging to either male or female persons in 6 percent of the cases only. The results of additional examinations made of 198 right humeri were less accurate and showed a decrease of the sexual dimorphism of bone with age.", "contents": "[The determination of age and sex from measure of the humerus (author's transl)]. On a total of seventy left humeri of persons in their third to ninth decades of life thirty different bone dimensions were determined macroscoically and checked for age dependence. Strong dependence on age was shown only by the weight and volume of the humerus as well as by the areal and thickness dimensins of the center of the shaft. These were used to set up multidimensional linear regression functions by which it is possible for the age of persons past thirty to be estimated with defined accuracy. Also calculated were discriminant functions which allow the sex of a person to be identified to be determined from three dimensions of the left humeral head, and these are the size of the caput at the cartilage-to-bone interface, the transverse and vertical diameters of the caput humeri or head of the humerus. Of the 49 cases studied only three were found to be in the region of overlap of the dimensions used for calculation. Consequently, the formula would not allow unknown humeri or skeletons, respectively, to be identified as belonging to either male or female persons in 6 percent of the cases only. The results of additional examinations made of 198 right humeri were less accurate and showed a decrease of the sexual dimorphism of bone with age."}
{"id": "PMID:203214", "title": "[Determination of free crystalline silica in atmospheric dust].", "content": "The method for the determination of free crystalline silica (quarts), as previously described by two of the authors, has been employed on atmosphere dust of unconfined spaces. The matrix effect of atmospheric dust has been investigated in winter and in summer. The limits in the use of this method have been studied considering also what stated by law code n. 615. The results obtained on the outdoor atmospheric dust, samples from industrial as well as suburban areas, are reported. The results are evaluated in relation to the metereological records.", "contents": "[Determination of free crystalline silica in atmospheric dust]. The method for the determination of free crystalline silica (quarts), as previously described by two of the authors, has been employed on atmosphere dust of unconfined spaces. The matrix effect of atmospheric dust has been investigated in winter and in summer. The limits in the use of this method have been studied considering also what stated by law code n. 615. The results obtained on the outdoor atmospheric dust, samples from industrial as well as suburban areas, are reported. The results are evaluated in relation to the metereological records."}
{"id": "PMID:203215", "title": "Humoral and cellular immune response during the growth of an SV40 induced tumour in hamsters.", "content": "Hamster fibroblasts transformed in vivo by the SV40 virus (TSV5Cl2) induce tumours when injected into adult hamsters and antibodies present in sera of tumour-bearing animals are used to demonstrate the presence of the antigens specific for the viral transformation. These tumours are a very useful tool in studying the evolution of the immune response during the tumour growth. A systematic histological examination of the spleen, thymus and lymph nodes was undertaken and the results thus obtained were correlated with a parallel study of the cells of the peritumoral region, the thymus and the spleen by immunofluorescence using antisera of different specificities. We were able to show that the plasma cells which make up the early peritumoral reaction and the lymphoblasts found later in spleen and thymus both synthesize antibodies directed against virus induced antigens. Circulating antibody directed against the same antigens is first detected at/or about the time that the peritumoral plasma cell reaction disappears and increases progressively as tumour weight increases.", "contents": "Humoral and cellular immune response during the growth of an SV40 induced tumour in hamsters. Hamster fibroblasts transformed in vivo by the SV40 virus (TSV5Cl2) induce tumours when injected into adult hamsters and antibodies present in sera of tumour-bearing animals are used to demonstrate the presence of the antigens specific for the viral transformation. These tumours are a very useful tool in studying the evolution of the immune response during the tumour growth. A systematic histological examination of the spleen, thymus and lymph nodes was undertaken and the results thus obtained were correlated with a parallel study of the cells of the peritumoral region, the thymus and the spleen by immunofluorescence using antisera of different specificities. We were able to show that the plasma cells which make up the early peritumoral reaction and the lymphoblasts found later in spleen and thymus both synthesize antibodies directed against virus induced antigens. Circulating antibody directed against the same antigens is first detected at/or about the time that the peritumoral plasma cell reaction disappears and increases progressively as tumour weight increases."}
{"id": "PMID:203216", "title": "Immunoprophylaxis of experimental cytomegalovirus infection.", "content": "Experimental MCMV infection simulates human disease. Since human CMV has no experimental animal, the murine model is useful to study mechanism of immunity to CMV and immunoprophylaxis of CMV infection. The live attenuated MCMV, obtained by serial passages in MEF, was effective in immunization of mice against fatal MCMV infection. Every parameter of the MCMV infection was nullified by the prior immunization. The protective immunity was cell-mediated and independent of antibody production. The sensitized T lymphocyte interfered with virus replication in vitro and in vivo. Efficacy and possible risk of a human CMV vaccine were discussed with the murine model.", "contents": "Immunoprophylaxis of experimental cytomegalovirus infection. Experimental MCMV infection simulates human disease. Since human CMV has no experimental animal, the murine model is useful to study mechanism of immunity to CMV and immunoprophylaxis of CMV infection. The live attenuated MCMV, obtained by serial passages in MEF, was effective in immunization of mice against fatal MCMV infection. Every parameter of the MCMV infection was nullified by the prior immunization. The protective immunity was cell-mediated and independent of antibody production. The sensitized T lymphocyte interfered with virus replication in vitro and in vivo. Efficacy and possible risk of a human CMV vaccine were discussed with the murine model."}
{"id": "PMID:203217", "title": "Factors concerning the immunity to poxvirus infection.", "content": "Two kinds of early antigens were shown in vaccinia-infected cells, one heat (56 degrees, 30 min)-stable (ES antigen) and the other heat-labile (EL antigen). Both antigens do not induce circulating neutralizing antibody in rabbits, but resistance to intradermal inoculation of active virus was observed when animals were immunized with either antigen in combination with Freund's complete adjuvant. Vaccinia-specific haemagglutinin (VHA) associated with infected cell membrane was purified and its antigenicity was also studied. Rabbits showed a good antibody response to VHA and some animals also showed neutralizing antibody, though in a small amount, to either intracellular (ICV) or extracellular (EVC) virus. Rabbits immunized with membrane antigens obtained from either VHA-positive or negative virus in combination with Freund's adjuvant showed skin restance to challenge with active virus. It was suggested that antibody against ECV might be responsible for the resistance.", "contents": "Factors concerning the immunity to poxvirus infection. Two kinds of early antigens were shown in vaccinia-infected cells, one heat (56 degrees, 30 min)-stable (ES antigen) and the other heat-labile (EL antigen). Both antigens do not induce circulating neutralizing antibody in rabbits, but resistance to intradermal inoculation of active virus was observed when animals were immunized with either antigen in combination with Freund's complete adjuvant. Vaccinia-specific haemagglutinin (VHA) associated with infected cell membrane was purified and its antigenicity was also studied. Rabbits showed a good antibody response to VHA and some animals also showed neutralizing antibody, though in a small amount, to either intracellular (ICV) or extracellular (EVC) virus. Rabbits immunized with membrane antigens obtained from either VHA-positive or negative virus in combination with Freund's adjuvant showed skin restance to challenge with active virus. It was suggested that antibody against ECV might be responsible for the resistance."}
{"id": "PMID:203219", "title": "Skeletal maturity of the hand and wrist in Japanese children in Sapporo by the TW2 method.", "content": "Skeletal maturity of Japanese children aged 6--18 years in Sapporo was compared with that of Japanese children in Toko, as well as with that of British children, by the TW2 method. In Sapporo children, the mean skeletal age was in advance of the chronological age after ages 12 years in boys and 10 years in girls. The ages at which the skeletal age preceded the chronological age occurred earlier in the children in Tokyo than in Sapporo. The hand and wrist bones completed maturation about the same age in both Japanese and British children. Somatometric and radiological results agreed exactly.", "contents": "Skeletal maturity of the hand and wrist in Japanese children in Sapporo by the TW2 method. Skeletal maturity of Japanese children aged 6--18 years in Sapporo was compared with that of Japanese children in Toko, as well as with that of British children, by the TW2 method. In Sapporo children, the mean skeletal age was in advance of the chronological age after ages 12 years in boys and 10 years in girls. The ages at which the skeletal age preceded the chronological age occurred earlier in the children in Tokyo than in Sapporo. The hand and wrist bones completed maturation about the same age in both Japanese and British children. Somatometric and radiological results agreed exactly."}
{"id": "PMID:203222", "title": "A new placental protein test for the presence and identification of trophoblastic tumors.", "content": "Trophoblast-specific beta1-glycoprotein (TSG) is detected in serum of patients with trophoblastic and nontrophoblastic tumors by means of immunodiffusion in agar (IDF), immunoradioautography in agar (IRA), and double-antibody radioimmunoassay (RIA), The identification of TSG is carried out by monospecific rabbit antisera. By IRA, TSG was found in serum of patients with trophoblastic tumors both before treatment (82.4%) and after surgery and/or chemotherapy (37.2%). All so-called falsepositives were associated with teratocarcinoma of the testicle. By means of RIA, TSG was also discovered in serum of patients with a variety of malignancies. In total, the TSG level was elevated in 15% of 114 cases of nontrophoblastic malignancies; as a rule, from 3 to 12 ng/ml. TSG was not detected in normal adult blood sera and in different pathological conditions.", "contents": "A new placental protein test for the presence and identification of trophoblastic tumors. Trophoblast-specific beta1-glycoprotein (TSG) is detected in serum of patients with trophoblastic and nontrophoblastic tumors by means of immunodiffusion in agar (IDF), immunoradioautography in agar (IRA), and double-antibody radioimmunoassay (RIA), The identification of TSG is carried out by monospecific rabbit antisera. By IRA, TSG was found in serum of patients with trophoblastic tumors both before treatment (82.4%) and after surgery and/or chemotherapy (37.2%). All so-called falsepositives were associated with teratocarcinoma of the testicle. By means of RIA, TSG was also discovered in serum of patients with a variety of malignancies. In total, the TSG level was elevated in 15% of 114 cases of nontrophoblastic malignancies; as a rule, from 3 to 12 ng/ml. TSG was not detected in normal adult blood sera and in different pathological conditions."}
{"id": "PMID:203224", "title": "[Quantitative amino acid makeup and the characteristics of the amino groups of ristomycin and the products of its partial acid hydrolysis].", "content": "The quantitative amino acid composition of ristomycin A, a glycopeptide antibiotic, peptides I-IV (from partial acid hydrolysis of the antibiotic) and their dinitrophenylic derivatives was determined. It was shown that both ristomycin and free peptides I-IV contained one residue of ristomycinic acid and one residue of actinoidinic acid, diamino-dicarbonic amino acids of the glycylphenolic type. Peptides I-IV had close molecular weights, i.e. 1100-1200 and differed from each other in the gradually increasing numbers of NH2- and COON- groups, from one in peptide I to four in peptide IV. The quantitative amino acid analysis of the dinitrophenylic derivatives of ristomycin and peptides I-IV showed that the free NH2-group in peptide I belonged to ristomycinic acid, the same as in the antibiotic, while in peptides III-IV at least one of the free NH2-groups belonged to ristomycinic acid and the other belonged to actinoidinic acid.", "contents": "[Quantitative amino acid makeup and the characteristics of the amino groups of ristomycin and the products of its partial acid hydrolysis]. The quantitative amino acid composition of ristomycin A, a glycopeptide antibiotic, peptides I-IV (from partial acid hydrolysis of the antibiotic) and their dinitrophenylic derivatives was determined. It was shown that both ristomycin and free peptides I-IV contained one residue of ristomycinic acid and one residue of actinoidinic acid, diamino-dicarbonic amino acids of the glycylphenolic type. Peptides I-IV had close molecular weights, i.e. 1100-1200 and differed from each other in the gradually increasing numbers of NH2- and COON- groups, from one in peptide I to four in peptide IV. The quantitative amino acid analysis of the dinitrophenylic derivatives of ristomycin and peptides I-IV showed that the free NH2-group in peptide I belonged to ristomycinic acid, the same as in the antibiotic, while in peptides III-IV at least one of the free NH2-groups belonged to ristomycinic acid and the other belonged to actinoidinic acid."}
{"id": "PMID:203225", "title": "[Experimental study of the antiviral properties of antibiotic 6734-21].", "content": "The effect of antibiotic 6734-21 on the viruses of variolovaccine, Herpes simplex, influenza and classical avian plague was studied on various experimental models. Antibiotic 6734-21 inhibited development of the variolovaccine virus in the tissue culture, in chick embryos, in rabbits with variolovaccine infection, as well as the development of the viruses of Herpes simplex, Aueski, and Newcastle diseases in the tissue culture. It had a virulicidic effect on the viruses of variolovaccine, influenza and classical avian plague.", "contents": "[Experimental study of the antiviral properties of antibiotic 6734-21]. The effect of antibiotic 6734-21 on the viruses of variolovaccine, Herpes simplex, influenza and classical avian plague was studied on various experimental models. Antibiotic 6734-21 inhibited development of the variolovaccine virus in the tissue culture, in chick embryos, in rabbits with variolovaccine infection, as well as the development of the viruses of Herpes simplex, Aueski, and Newcastle diseases in the tissue culture. It had a virulicidic effect on the viruses of variolovaccine, influenza and classical avian plague."}
{"id": "PMID:203227", "title": "Large-scale production and concentration of infectious Epstein-Barr virus.", "content": "Infectious Epstein-Barr virus (EBV) was produced from suspension cultures of P3HR-1 cells. A protocol for the scaled-up production and concentration of the virus was developed. Virus from the culture fluid was concentrated by continuous-flow pelletization or continuous flow with banding in sucrose. EBV prepared by pelletization yielded 1.7 X 10(4) infectious units/ml (100 X concentration) and less than 3.4 X  10(7) EVB particles/ml (1,000 X concentration), whereas EBV prepared by banding yielded 4.6 X 10(3) infectious units/ml (100 X concentration) aand 1.3 X 10(8) EBV particles 1 ml (1,000 X concentration). The majority of the virus particles observed were \"empty\" membrane-associated particles. A statistical test of the correlation between infectivity and virus particle count was made.", "contents": "Large-scale production and concentration of infectious Epstein-Barr virus. Infectious Epstein-Barr virus (EBV) was produced from suspension cultures of P3HR-1 cells. A protocol for the scaled-up production and concentration of the virus was developed. Virus from the culture fluid was concentrated by continuous-flow pelletization or continuous flow with banding in sucrose. EBV prepared by pelletization yielded 1.7 X 10(4) infectious units/ml (100 X concentration) and less than 3.4 X  10(7) EVB particles/ml (1,000 X concentration), whereas EBV prepared by banding yielded 4.6 X 10(3) infectious units/ml (100 X concentration) aand 1.3 X 10(8) EBV particles 1 ml (1,000 X concentration). The majority of the virus particles observed were \"empty\" membrane-associated particles. A statistical test of the correlation between infectivity and virus particle count was made."}
{"id": "PMID:203233", "title": "Minimal breast cancer: a clinical appraisal.", "content": "Eighty-five patients with a diagnosis of minimal breast cancer were evaluated. The predominant lesion was intraductal carcinoma, and axillary metastases occurred in association with minimal breast cancer in seven of 96 cases. One death occurred due to minimal breast cancer. Bilateral mammary carcinoma was evident in 24% and bilateral minimal breast cancer in 13% of the patients. The component lesions of minimal breast cancer have varied biologic activity, but prognosis is good with a variety of operations. The multifocal nature of minimal breast cancer and the potential for metastases should be recognized. Therapy should include removal of the entire mammary parenchyma and low axillary nodes. The high incidence of bilateral malignancy supports elective contralateral biopsy at the time of therapy for minimal breast cancer.", "contents": "Minimal breast cancer: a clinical appraisal. Eighty-five patients with a diagnosis of minimal breast cancer were evaluated. The predominant lesion was intraductal carcinoma, and axillary metastases occurred in association with minimal breast cancer in seven of 96 cases. One death occurred due to minimal breast cancer. Bilateral mammary carcinoma was evident in 24% and bilateral minimal breast cancer in 13% of the patients. The component lesions of minimal breast cancer have varied biologic activity, but prognosis is good with a variety of operations. The multifocal nature of minimal breast cancer and the potential for metastases should be recognized. Therapy should include removal of the entire mammary parenchyma and low axillary nodes. The high incidence of bilateral malignancy supports elective contralateral biopsy at the time of therapy for minimal breast cancer."}
{"id": "PMID:203234", "title": "Evaluation of cardiac ischemia by NADH fluroescence photography.", "content": "A direct, noninvasive method of assessing the oxidation-reduction potential of an intramyocardial respiratory chain component is described. The technique is based on the differences in spectral properties between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NADH). The tissue surface fluorescence from intracellular NADH may be measured and documented photographically. Noose occlusion of a coronary artery produced detectable NADH fluorescence in 15 seconds in the subtended ischemic epicardium. This fluorescence of reduced pyridine nucleotide resolved following 60 seconds of reperfusion of the ischemic myocardium. The reduction of epicardial NADH with ischemia is a rapid and reversible process. A subsequent noose reocclusion resulted in a reproducible pattern of fluorescence. The technique of NADH fluorescence photography appears superior to current methods of assessing tissue oxygen supply:demand.", "contents": "Evaluation of cardiac ischemia by NADH fluroescence photography. A direct, noninvasive method of assessing the oxidation-reduction potential of an intramyocardial respiratory chain component is described. The technique is based on the differences in spectral properties between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NADH). The tissue surface fluorescence from intracellular NADH may be measured and documented photographically. Noose occlusion of a coronary artery produced detectable NADH fluorescence in 15 seconds in the subtended ischemic epicardium. This fluorescence of reduced pyridine nucleotide resolved following 60 seconds of reperfusion of the ischemic myocardium. The reduction of epicardial NADH with ischemia is a rapid and reversible process. A subsequent noose reocclusion resulted in a reproducible pattern of fluorescence. The technique of NADH fluorescence photography appears superior to current methods of assessing tissue oxygen supply:demand."}
{"id": "PMID:203235", "title": "The beta-adrenergic activity of some monosubstituted phenethanolamines.", "content": "A series of monosubstituted phenethanolamines with N-isopropyl and N-tert-butyl substituents has been prepared. A detailed pharmacological study has been made of the beta-adrenergic activity of these materials as the nitrogen substituent and the nature and position of the phenyl substituent were changed, and their selectivity has been determined for beta1- and beta2-adrenoceptors in guinea-pig and cat tissues.", "contents": "The beta-adrenergic activity of some monosubstituted phenethanolamines. A series of monosubstituted phenethanolamines with N-isopropyl and N-tert-butyl substituents has been prepared. A detailed pharmacological study has been made of the beta-adrenergic activity of these materials as the nitrogen substituent and the nature and position of the phenyl substituent were changed, and their selectivity has been determined for beta1- and beta2-adrenoceptors in guinea-pig and cat tissues."}
{"id": "PMID:203236", "title": "A comparative study of the beta-adrenoceptors of guinea-pig, rabbit and rat trachea.", "content": "The sensitivity to isoprenaline of beta inhibitory adrenoceptors of tracheal chain preparations from guinea-pig, rabbit and rat was compared. For this purpose the tracheal chain preparations were contracted either with KCl or pilocarpine. Isoprenaline (1.0 X 10(-7)M--6.4 X 10(-6)M) caused concentration-related relaxation of guinea-pig trachea, whereas the rabbit and the rat trachea remained insensitive even at very high concentrations of isoprenaline (2.5 X 10(-3)M). Phenoxybenzamine (2.6 X 10(-6)M) potentiated or unmasked the relaxant effects of isoprenaline respectively in the guinea-pig or the rabbit and the rat trachea contracted with KCl. Phentolamine was ineffective in potentiating or unmasking the relaxant effects of isoprenaline. The potentiating or unmasking effects of phenoxybenzamine were absent in reserpinized preparations and lidocaine treated preparations from both guinea-pig and rat. Normetanephrine (5.4 X 10(-7)M) potentiated responses to isoprenaline only in the guinea-pig trachea. Even a 10-fold higher concentration of normetanephrine was ineffective in the rabbit or the rat rachea.", "contents": "A comparative study of the beta-adrenoceptors of guinea-pig, rabbit and rat trachea. The sensitivity to isoprenaline of beta inhibitory adrenoceptors of tracheal chain preparations from guinea-pig, rabbit and rat was compared. For this purpose the tracheal chain preparations were contracted either with KCl or pilocarpine. Isoprenaline (1.0 X 10(-7)M--6.4 X 10(-6)M) caused concentration-related relaxation of guinea-pig trachea, whereas the rabbit and the rat trachea remained insensitive even at very high concentrations of isoprenaline (2.5 X 10(-3)M). Phenoxybenzamine (2.6 X 10(-6)M) potentiated or unmasked the relaxant effects of isoprenaline respectively in the guinea-pig or the rabbit and the rat trachea contracted with KCl. Phentolamine was ineffective in potentiating or unmasking the relaxant effects of isoprenaline. The potentiating or unmasking effects of phenoxybenzamine were absent in reserpinized preparations and lidocaine treated preparations from both guinea-pig and rat. Normetanephrine (5.4 X 10(-7)M) potentiated responses to isoprenaline only in the guinea-pig trachea. Even a 10-fold higher concentration of normetanephrine was ineffective in the rabbit or the rat rachea."}
{"id": "PMID:203237", "title": "The influence of light and different ATP concentrations on cell aggregation in cyclic AMP sensitive and insensitive species of the cellular slime molds.", "content": "The influence of light and different concentrations of ATP on cell aggregation in cyclic AMP sensitive (Dictyostelium mucoroides, D. purpureum) and cyclic AMP insensitive species (Polysphondylium violaceum, P. pallidum, D. lacteum) of the cellular slime molds was observed in small and in large amoebal populations. Both light and ATP (optimal concentration: 10(-5) M) accelerated cell aggregation and increased the number of aggregating centers in large populations. For cyclic AMP sensitive species the effect of ATP in large populations was more pronounced than for the species that do not react to cyclic AMP. A possible explanation for the similar effect of light and ATP has been discussed.", "contents": "The influence of light and different ATP concentrations on cell aggregation in cyclic AMP sensitive and insensitive species of the cellular slime molds. The influence of light and different concentrations of ATP on cell aggregation in cyclic AMP sensitive (Dictyostelium mucoroides, D. purpureum) and cyclic AMP insensitive species (Polysphondylium violaceum, P. pallidum, D. lacteum) of the cellular slime molds was observed in small and in large amoebal populations. Both light and ATP (optimal concentration: 10(-5) M) accelerated cell aggregation and increased the number of aggregating centers in large populations. For cyclic AMP sensitive species the effect of ATP in large populations was more pronounced than for the species that do not react to cyclic AMP. A possible explanation for the similar effect of light and ATP has been discussed."}
{"id": "PMID:203239", "title": "Metabolic regulation in Pseudomonas oxalaticus OX1. Enzyme and coenzyme concentration changes during substrate transition experiments.", "content": "Metabolic control associated with diauxic growth of Pseudomonas oxalaticus in batch cultures on mixtures of formate and oxalate was investigated by measuring intracellular enzyme and coenzyme concentrations and QO2 values during transition experiments from oxalate to formate and vice versa. In transition from oxalate to formate oxalyl-CoA reductase concentration declined after the exhaustion of oxalate and ribulose-1,5-diphosphate carboxylase and 14CO2 fixation appeared upon addition of formate. In the reciprocal transition, ribulose-1,5-diphosphate carboxylase and 14CO2 fixation rate declined sharply after formate exhaustion, and oxalyl-CoA reductase appeared only after addition of oxalate. The intracellular NAD and NADP concentrations measured in the same experiments are reported. At substrate exhaustion the proportion of NAD in the reduced form fell from 15-20% to 2%. On addition of formate to an oxalate-starved culture there was an immediate increase in the proportion of NADH to 50%; such an increase was not observed in the reverse experiment.", "contents": "Metabolic regulation in Pseudomonas oxalaticus OX1. Enzyme and coenzyme concentration changes during substrate transition experiments. Metabolic control associated with diauxic growth of Pseudomonas oxalaticus in batch cultures on mixtures of formate and oxalate was investigated by measuring intracellular enzyme and coenzyme concentrations and QO2 values during transition experiments from oxalate to formate and vice versa. In transition from oxalate to formate oxalyl-CoA reductase concentration declined after the exhaustion of oxalate and ribulose-1,5-diphosphate carboxylase and 14CO2 fixation appeared upon addition of formate. In the reciprocal transition, ribulose-1,5-diphosphate carboxylase and 14CO2 fixation rate declined sharply after formate exhaustion, and oxalyl-CoA reductase appeared only after addition of oxalate. The intracellular NAD and NADP concentrations measured in the same experiments are reported. At substrate exhaustion the proportion of NAD in the reduced form fell from 15-20% to 2%. On addition of formate to an oxalate-starved culture there was an immediate increase in the proportion of NADH to 50%; such an increase was not observed in the reverse experiment."}
{"id": "PMID:203238", "title": "The alternate respiratory pathway of Candida albicans.", "content": "Candida albicans contains a cryptic cyanide and antimycin A insensitive respiratory system. This alternate oxidase was found (i) at all growth rates from mu = 0.05 to 0.26 in a chemostat culture and (ii) in both mycelial and yeast forms of the organism. Neither chloramphenicol nor cycloheximide prevented the expression of the alternate oxidase. Salicylhydroxamic acid was a potent inhibitor of the cyanide insensitive respiration. The respiration of mitochondria grown in the presence of antimycin A was not inhibited by cyanide or antimycin A but was inhibited by salicylhydroxamic acid.", "contents": "The alternate respiratory pathway of Candida albicans. Candida albicans contains a cryptic cyanide and antimycin A insensitive respiratory system. This alternate oxidase was found (i) at all growth rates from mu = 0.05 to 0.26 in a chemostat culture and (ii) in both mycelial and yeast forms of the organism. Neither chloramphenicol nor cycloheximide prevented the expression of the alternate oxidase. Salicylhydroxamic acid was a potent inhibitor of the cyanide insensitive respiration. The respiration of mitochondria grown in the presence of antimycin A was not inhibited by cyanide or antimycin A but was inhibited by salicylhydroxamic acid."}
{"id": "PMID:203241", "title": "[Causes for species difference in acute toxicity of chlorocholine chloride].", "content": "Chlorocholine chloride (CCC) inhibits neuromuscular transduction of excitation and, consequently, leads to respiratory arrest in cases of acute intoxication. An account is given of the relationships between neuromuscularly blocking activity and acute toxicity of CCC. Several animal species and pharmacological models are used to produce evidence to the effect that CCC-caused inhibition of neuromuscular transmission of excitation is characterised by parameters typical of block due to depolarisation. The differentiated sensitivity of species to depolarising neuromuscular blockers is thought to be the decisive cause of species differences regarding acute toxicity of CCC. Conclusions are discussed which may be derived from the above findings regarding acute CCC toxicity to man and agricultural animal.", "contents": "[Causes for species difference in acute toxicity of chlorocholine chloride]. Chlorocholine chloride (CCC) inhibits neuromuscular transduction of excitation and, consequently, leads to respiratory arrest in cases of acute intoxication. An account is given of the relationships between neuromuscularly blocking activity and acute toxicity of CCC. Several animal species and pharmacological models are used to produce evidence to the effect that CCC-caused inhibition of neuromuscular transmission of excitation is characterised by parameters typical of block due to depolarisation. The differentiated sensitivity of species to depolarising neuromuscular blockers is thought to be the decisive cause of species differences regarding acute toxicity of CCC. Conclusions are discussed which may be derived from the above findings regarding acute CCC toxicity to man and agricultural animal."}
{"id": "PMID:203242", "title": "[Experimental infection of man using viral strains of bovine papular stomatitis, orf, pseudocowpox and milker's nodule].", "content": "An account is given of the close correlations that exist between virus strains of bovine papular stomatitis, orf, pseudocowpox, and milker's nodule. Reference is made to literature data on natural infection of man with the above virus strains. A report then is presented on experimental infection of human volunteers, using paravaccine birus. While fairly tough and elevated nodules, 4 mm to 5 mm in diameter, were produced on the probends' skin, no re-isolation of virus was achieved.", "contents": "[Experimental infection of man using viral strains of bovine papular stomatitis, orf, pseudocowpox and milker's nodule]. An account is given of the close correlations that exist between virus strains of bovine papular stomatitis, orf, pseudocowpox, and milker's nodule. Reference is made to literature data on natural infection of man with the above virus strains. A report then is presented on experimental infection of human volunteers, using paravaccine birus. While fairly tough and elevated nodules, 4 mm to 5 mm in diameter, were produced on the probends' skin, no re-isolation of virus was achieved."}
{"id": "PMID:203246", "title": "Inorganic cytoplasmic inclusions in alveolar macrophages. The role of cigarette smoking.", "content": "A case of tobacco-associated pulmonary fibrosis, with the results of histological, ultrastructural, and spectrometric analysis is reported. Abnormalities of the alveolar macrophages, which are particularly affected by tobacco inhalation were found. The size of the macrophages was increased and many large, polymorphous inclusions, including fat vacuoles and granular deposits, which were either homogeneous or electron lucent vacuoles, were seen in the cytoplasm. A few laminar structures were observed. All of these lesions are frequently found in cigarette smokers. Still more interesting was the discovery of numerous fiber-, needle-, or laminar-like inclusions that varied in size from 0.2 to more than 2 mu. The digestions of the inclusions with potassium hydroxide confirmed the presence of various metals, such as sodium, magnesium, potassium, iron, sulfur, and especially, aluminum, and silicon; these last two elements correspond to the presence of kaolinite in the tissue, as has been previously described, and can be considered as evidence of the use of tobacco.", "contents": "Inorganic cytoplasmic inclusions in alveolar macrophages. The role of cigarette smoking. A case of tobacco-associated pulmonary fibrosis, with the results of histological, ultrastructural, and spectrometric analysis is reported. Abnormalities of the alveolar macrophages, which are particularly affected by tobacco inhalation were found. The size of the macrophages was increased and many large, polymorphous inclusions, including fat vacuoles and granular deposits, which were either homogeneous or electron lucent vacuoles, were seen in the cytoplasm. A few laminar structures were observed. All of these lesions are frequently found in cigarette smokers. Still more interesting was the discovery of numerous fiber-, needle-, or laminar-like inclusions that varied in size from 0.2 to more than 2 mu. The digestions of the inclusions with potassium hydroxide confirmed the presence of various metals, such as sodium, magnesium, potassium, iron, sulfur, and especially, aluminum, and silicon; these last two elements correspond to the presence of kaolinite in the tissue, as has been previously described, and can be considered as evidence of the use of tobacco."}
{"id": "PMID:203247", "title": "Malignant thymic tumor in an infant (malignant histiocytoma).", "content": "A 2-month-old infant was diagnosed as having an invasive thymic tumor. Histologically and ultrastructurally, the tumor was composed of primitive mesenchymal cells, most likely malignant histiocytes. The child died at the age of 5 1/2 months with metastases to the bone and and liver. Review of the literature on thymic tumors and fibrous histiocytomas or malignant histiocytoma shows no similar case.", "contents": "Malignant thymic tumor in an infant (malignant histiocytoma). A 2-month-old infant was diagnosed as having an invasive thymic tumor. Histologically and ultrastructurally, the tumor was composed of primitive mesenchymal cells, most likely malignant histiocytes. The child died at the age of 5 1/2 months with metastases to the bone and and liver. Review of the literature on thymic tumors and fibrous histiocytomas or malignant histiocytoma shows no similar case."}
{"id": "PMID:203248", "title": "Phosphatase enzymes. Cytochemical study of pleomorphic adenoma and normal human salivary glands.", "content": "Human parotid glands, submandibular glands, and pleomorphic adenomas were examined by electron microscopic histochemistry. All epithelial cells of the normal salivary glands showed plasma membrane adenosine triphosphatase (ATPase) and inosine diphosphatase (IDPase) activity. However, myoepithelial cells reacted most intensely. Pleomorphic adenomas showed epithelial cells within solid and ductal portions of the tumors that were variably reactive for both ATPase and IDPase. Histochemical examination of the epithelial cells in the myxoid portions of the tumors did not provide conclusive evidence as to the nature of their progenitor cells. Surface-associated phosphatases (alkaline phosphatase, ATPase, and IDPase) cannot be reliably used as histochemical markers of salivary gland myoepithelial cells. Therefore, morphological and phosphatase histochemical studies that intend to examine the role of myoepithelial cells in salivary gland neoplasms must be interpreted with care.", "contents": "Phosphatase enzymes. Cytochemical study of pleomorphic adenoma and normal human salivary glands. Human parotid glands, submandibular glands, and pleomorphic adenomas were examined by electron microscopic histochemistry. All epithelial cells of the normal salivary glands showed plasma membrane adenosine triphosphatase (ATPase) and inosine diphosphatase (IDPase) activity. However, myoepithelial cells reacted most intensely. Pleomorphic adenomas showed epithelial cells within solid and ductal portions of the tumors that were variably reactive for both ATPase and IDPase. Histochemical examination of the epithelial cells in the myxoid portions of the tumors did not provide conclusive evidence as to the nature of their progenitor cells. Surface-associated phosphatases (alkaline phosphatase, ATPase, and IDPase) cannot be reliably used as histochemical markers of salivary gland myoepithelial cells. Therefore, morphological and phosphatase histochemical studies that intend to examine the role of myoepithelial cells in salivary gland neoplasms must be interpreted with care."}
{"id": "PMID:203249", "title": "Giant cell tumors of tendon sheath. An electron microscopical study of 11 cases.", "content": "Light and electron microscopy of 11 giant cell tumors of tendon sheath revealed a pleomorphic cell population in which the giant cells had similarities to osteoclasts, and the stromal cells had similarities to primitive mesenchymal cells, osteoblasts, fibroblasts, and histiocytes. I suggest that giant cell tumors of tendon sheath are derived from mesenchymal cells with partial osseous differentiation.", "contents": "Giant cell tumors of tendon sheath. An electron microscopical study of 11 cases. Light and electron microscopy of 11 giant cell tumors of tendon sheath revealed a pleomorphic cell population in which the giant cells had similarities to osteoclasts, and the stromal cells had similarities to primitive mesenchymal cells, osteoblasts, fibroblasts, and histiocytes. I suggest that giant cell tumors of tendon sheath are derived from mesenchymal cells with partial osseous differentiation."}
{"id": "PMID:203251", "title": "[Metastasis of breast cancer (according to findings of the pathologist of the I. M. Sechenov Moscow Medical Institute I during the 25 year period -- 1951-1975)].", "content": "The mammary gland cancer metastasizes most frequently into lymph nodes, the liver, bones, lungs and adrenal glands. Calculations of the combined coefficient of metastasizing showed the adenocarcinoma more frequently than other forms to metastasize into the lymph nodes of the chest, adrenals, and kidneys and less frequently into the liver; solid carcinoma with pseudoepidermoid metaplasia metastasizes into the brain more frequently than the other forms. The longest average survival after treatment (radical mastectomy, radiation therapy) was established in a more differentiated form of cancer - adenocarcinoma; the survival time after solid carcinoma and fibrous cancer is considerably shorter.", "contents": "[Metastasis of breast cancer (according to findings of the pathologist of the I. M. Sechenov Moscow Medical Institute I during the 25 year period -- 1951-1975)]. The mammary gland cancer metastasizes most frequently into lymph nodes, the liver, bones, lungs and adrenal glands. Calculations of the combined coefficient of metastasizing showed the adenocarcinoma more frequently than other forms to metastasize into the lymph nodes of the chest, adrenals, and kidneys and less frequently into the liver; solid carcinoma with pseudoepidermoid metaplasia metastasizes into the brain more frequently than the other forms. The longest average survival after treatment (radical mastectomy, radiation therapy) was established in a more differentiated form of cancer - adenocarcinoma; the survival time after solid carcinoma and fibrous cancer is considerably shorter."}
{"id": "PMID:203253", "title": "Corpora amylacea of the lumbar spinal cord and peripheral nervous system.", "content": "Tissue from L-4 spinal cord, dorsal root ganglia, sural nerve, and intramuscular branches to the gastrocnemius was obtained during 35 random autopsies, embedded in paraffin, and stained with PAS and Holmes Alcian blue and studied for the incidence and distribution of corpora amylacea (CA). Intraaxonal CA in spinal grey matter were commonly found, but the incidence in root ganglia, sural, and intramuscular nerve was low. Clinically insignificant intraneuronal spinal grey CA were found in six of eight men past the age of 60 years. Corpora amylacea in spinal white matter were most common in the region of posterior root entry.", "contents": "Corpora amylacea of the lumbar spinal cord and peripheral nervous system. Tissue from L-4 spinal cord, dorsal root ganglia, sural nerve, and intramuscular branches to the gastrocnemius was obtained during 35 random autopsies, embedded in paraffin, and stained with PAS and Holmes Alcian blue and studied for the incidence and distribution of corpora amylacea (CA). Intraaxonal CA in spinal grey matter were commonly found, but the incidence in root ganglia, sural, and intramuscular nerve was low. Clinically insignificant intraneuronal spinal grey CA were found in six of eight men past the age of 60 years. Corpora amylacea in spinal white matter were most common in the region of posterior root entry."}
{"id": "PMID:203255", "title": "Herpes simplex virus types 1 and 2 in ocular disease.", "content": "In a continuous series of 457 patients with presumed herpetic eye disease, virus isolation and typing revealed 154 patients with herpes simplex virus type 1 and three patients with type 2 infections. In 219 isolates that were examined for neutralization by specific antisera, for growth in human fibroblasts, and, in part, for temperature sensitivity, there were found substantial strain differences in addition to the type-specific characteristics. The clinical features of each of the three type 2 infections are described in detail. A suggestive correlation found between clinical courses and virus growth characteristics of the type 1 strains indicates that further virologic differentiation of these strains would be useful.", "contents": "Herpes simplex virus types 1 and 2 in ocular disease. In a continuous series of 457 patients with presumed herpetic eye disease, virus isolation and typing revealed 154 patients with herpes simplex virus type 1 and three patients with type 2 infections. In 219 isolates that were examined for neutralization by specific antisera, for growth in human fibroblasts, and, in part, for temperature sensitivity, there were found substantial strain differences in addition to the type-specific characteristics. The clinical features of each of the three type 2 infections are described in detail. A suggestive correlation found between clinical courses and virus growth characteristics of the type 1 strains indicates that further virologic differentiation of these strains would be useful."}
{"id": "PMID:203256", "title": "Iris metastasis from a bronchial carcinoid tumor.", "content": "A 54-year-old man had a fleshy pink vascularized mass in the superonasal quadrant of the right iris. He had a history of an unchanging pulmonary nodule that was followed up for five years with routine chest roentgenograms. Fluorescein angiography demonstrated early filling of numerous fine blood vessels in the mass and diffuse late staining of the lesion. Results of a transcorneal radioactive phosphorus (32P) uptake test were positive. The clinical diagnosis was tapioca melanoma of the iris, with metastatic tumor as a second possibility. The tumor was excised by iridocyclectomy. Light microscopy revealed nests of tumor cells with oval hyperchromatic nuclei. Fontana stains for melanin were negative as were argentaffin and argyrophil strans. Electron microscopy demonstrated light and dark tumor cells containing numerous membrane-bound electron-dense neurosecretory granules. The diagnosis was iris metastasis from a probable bronchial carcinoid. The patient is alive and well years after excision of the iris mass.", "contents": "Iris metastasis from a bronchial carcinoid tumor. A 54-year-old man had a fleshy pink vascularized mass in the superonasal quadrant of the right iris. He had a history of an unchanging pulmonary nodule that was followed up for five years with routine chest roentgenograms. Fluorescein angiography demonstrated early filling of numerous fine blood vessels in the mass and diffuse late staining of the lesion. Results of a transcorneal radioactive phosphorus (32P) uptake test were positive. The clinical diagnosis was tapioca melanoma of the iris, with metastatic tumor as a second possibility. The tumor was excised by iridocyclectomy. Light microscopy revealed nests of tumor cells with oval hyperchromatic nuclei. Fontana stains for melanin were negative as were argentaffin and argyrophil strans. Electron microscopy demonstrated light and dark tumor cells containing numerous membrane-bound electron-dense neurosecretory granules. The diagnosis was iris metastasis from a probable bronchial carcinoid. The patient is alive and well years after excision of the iris mass."}
{"id": "PMID:203257", "title": "[Pathophysiology and metabolism in osteogenesis imperfecta (author's transl)].", "content": "The tissue changes in osteogenesis imperfecta apparently lie in the collagen and in the glycosaminoglycans. The collagen shows structural development disturbance and incomplete calcification. The tissue glycosaminoglycans are increased. The basis probably lies in a disturbed ATP metabolism (Solomons and Millar, 1973). An increased pyrophosphate concentration explains the decreased calcification and the structural changes. The increased osteolysis could be explained by increased quantities of cAMP.", "contents": "[Pathophysiology and metabolism in osteogenesis imperfecta (author's transl)]. The tissue changes in osteogenesis imperfecta apparently lie in the collagen and in the glycosaminoglycans. The collagen shows structural development disturbance and incomplete calcification. The tissue glycosaminoglycans are increased. The basis probably lies in a disturbed ATP metabolism (Solomons and Millar, 1973). An increased pyrophosphate concentration explains the decreased calcification and the structural changes. The increased osteolysis could be explained by increased quantities of cAMP."}
{"id": "PMID:203258", "title": "[Studies of the mucopolysaccharid metabolism in the juvenile angiofibroma (author's transl)].", "content": "The mucopolysaccharide content of juvenile angiofibromas is investigated using histochemical and ultrahistochemical methods (histochemical in ten cases, ultrahistochemical in four cases). The investigations result in typical histochemical features and show the localization of acid mucopolysaccharides at electronmicroscopical level. The endothelium of the vessels exhibits a strong PAS-reaction and also shows acid groups at the cell surfaces. The interstitial tissue demonstrates neutral perjodatreactive substances as well as acid mucopolysaccharides. The latter substances mainly reacted in perifibrillar position. Electronmicroscopically the perjodreactive material was localized in the cytoplasma of typical fibroblasts and their modulations resembling histiocytes. The acid groups of carboxylated and sulfated mucopolysaccharides of the intercellular substance could be determined as hyaluronic acides and chondroitinsulfates (Chondroitin-4 and Chondroitin-6 sulfate) using the critical-electrolyte-concentration method after Scott and Dorling. Ultrastructurally these acid groups are localized as cell coat covering the fibroblasts and between the collagen fibrils. This histochemical investigation also supports the thesis of an organoid growth pattern of juvenile angiofibroma.", "contents": "[Studies of the mucopolysaccharid metabolism in the juvenile angiofibroma (author's transl)]. The mucopolysaccharide content of juvenile angiofibromas is investigated using histochemical and ultrahistochemical methods (histochemical in ten cases, ultrahistochemical in four cases). The investigations result in typical histochemical features and show the localization of acid mucopolysaccharides at electronmicroscopical level. The endothelium of the vessels exhibits a strong PAS-reaction and also shows acid groups at the cell surfaces. The interstitial tissue demonstrates neutral perjodatreactive substances as well as acid mucopolysaccharides. The latter substances mainly reacted in perifibrillar position. Electronmicroscopically the perjodreactive material was localized in the cytoplasma of typical fibroblasts and their modulations resembling histiocytes. The acid groups of carboxylated and sulfated mucopolysaccharides of the intercellular substance could be determined as hyaluronic acides and chondroitinsulfates (Chondroitin-4 and Chondroitin-6 sulfate) using the critical-electrolyte-concentration method after Scott and Dorling. Ultrastructurally these acid groups are localized as cell coat covering the fibroblasts and between the collagen fibrils. This histochemical investigation also supports the thesis of an organoid growth pattern of juvenile angiofibroma."}
{"id": "PMID:203259", "title": "Changes in ornithine decarboxylase activity and cyclic adenosine-3'-5'-monophosphate concentrations during the cell cycle of synchronized BHK cells.", "content": "BHK cells were synchronized by excess thymidine treatment, which resulted in approximately 90% synchrony. The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, elevated in early S phase, decreased in G2 + M and G1 phase and then increased during late G1 approximately second round of early S phase. The concentration of cyclic adenosine-3'-5'-monophosphate (cAMP) gradually decreased during S approximately G2 + M phase and then increased during late G1 approximately second round of early S phase, preceding that of ODC activity. The data suggest that ODC activity might be regulated by cellular cAMP level.", "contents": "Changes in ornithine decarboxylase activity and cyclic adenosine-3'-5'-monophosphate concentrations during the cell cycle of synchronized BHK cells. BHK cells were synchronized by excess thymidine treatment, which resulted in approximately 90% synchrony. The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, elevated in early S phase, decreased in G2 + M and G1 phase and then increased during late G1 approximately second round of early S phase. The concentration of cyclic adenosine-3'-5'-monophosphate (cAMP) gradually decreased during S approximately G2 + M phase and then increased during late G1 approximately second round of early S phase, preceding that of ODC activity. The data suggest that ODC activity might be regulated by cellular cAMP level."}
{"id": "PMID:203260", "title": "Requirements for stimulation of T cell responses against virus-infected cells: nature of ectromelia virus-infected cells capable of stimulating cytotoxic T cells in a secondary response in vitro.", "content": "The nature of infected stimulator cells in the in vitro secondary cytotoxic T cell response to ectromelia infection was investigated. It was found that macrophages were better stimulator cells than spleen cells. B cells (Ig-positive cells) were superior to T cells (Ig-negative cells) both on a relative proportion and on a cell-to-cell basis. Concanavalin A and lipopolysaccharide-stimulated lymphocytes were also effective stimulator cells but appeared to be slightly inferior to spleen cells. Spleen cells depleted of Ia-positive cells were markedly inferior to normal spleen cells as stimulators. It was also found that primary and secondary cytotoxic T cells were largely Ia-negative. These findings are discussed in relation to the likely events during T cell responses to infection in vivo.", "contents": "Requirements for stimulation of T cell responses against virus-infected cells: nature of ectromelia virus-infected cells capable of stimulating cytotoxic T cells in a secondary response in vitro. The nature of infected stimulator cells in the in vitro secondary cytotoxic T cell response to ectromelia infection was investigated. It was found that macrophages were better stimulator cells than spleen cells. B cells (Ig-positive cells) were superior to T cells (Ig-negative cells) both on a relative proportion and on a cell-to-cell basis. Concanavalin A and lipopolysaccharide-stimulated lymphocytes were also effective stimulator cells but appeared to be slightly inferior to spleen cells. Spleen cells depleted of Ia-positive cells were markedly inferior to normal spleen cells as stimulators. It was also found that primary and secondary cytotoxic T cells were largely Ia-negative. These findings are discussed in relation to the likely events during T cell responses to infection in vivo."}
{"id": "PMID:203263", "title": "Investigations on the turnover of adrenocortical mitochondria. XI. Effects of dexamethasone on the half-life of mitochondria from the rat zona fasciculata.", "content": "The effects of dexamethasone on the half-life of rat adrenocortical mitochondria were investigated by high resolution autoradiography and liquid scintillation spectroscopy. According to the method employed, the half-life averaged 11.27 and 10.46 days. Dexamethasone was found to decrease significantly this parameter (to about 5 days). Since dexamethasone-treated rats can be regarded as pharmacologically hypophysectomized animals, the data indicates that ACTH is involved in the maintenance of the half-life of adrenocortical mitochondria.", "contents": "Investigations on the turnover of adrenocortical mitochondria. XI. Effects of dexamethasone on the half-life of mitochondria from the rat zona fasciculata. The effects of dexamethasone on the half-life of rat adrenocortical mitochondria were investigated by high resolution autoradiography and liquid scintillation spectroscopy. According to the method employed, the half-life averaged 11.27 and 10.46 days. Dexamethasone was found to decrease significantly this parameter (to about 5 days). Since dexamethasone-treated rats can be regarded as pharmacologically hypophysectomized animals, the data indicates that ACTH is involved in the maintenance of the half-life of adrenocortical mitochondria."}
{"id": "PMID:203265", "title": "Possible mitochondrial involvement in mechanism of cytoplasmic male sterility in maize (Zea mays L.).", "content": "The mechanism of cytoplasmic male sterility was investigated in maize by isolating mitochondria from seedlings and various anther stages and analyzing cytochrome oxidase and succinic dehydrogenase biochemically and electrophoretically. Sterile anthers exhibited a lack of biochemical activity and fewer isozymatic bands for cytochrome oxidase. No apparent differences were detected biochemically or electrophoretically between fertile and sterile anthers for succinate dehydrogenase.", "contents": "Possible mitochondrial involvement in mechanism of cytoplasmic male sterility in maize (Zea mays L.). The mechanism of cytoplasmic male sterility was investigated in maize by isolating mitochondria from seedlings and various anther stages and analyzing cytochrome oxidase and succinic dehydrogenase biochemically and electrophoretically. Sterile anthers exhibited a lack of biochemical activity and fewer isozymatic bands for cytochrome oxidase. No apparent differences were detected biochemically or electrophoretically between fertile and sterile anthers for succinate dehydrogenase."}
{"id": "PMID:203266", "title": "Regulation of the neutral phosphatase in Chlamydomonas reinhardi: an immunogenetic study of wild-type and mutant strains.", "content": "In Chlamydomonas reinhardi, the activity of the neutral phosphatase considerably increases when the cells are grown in the absence of inorganic phosphate (Pi). A comparative immunological study of cells grown on media containing Pi or not indicated that the neutral phosphatase was synthesized de novo. Ten mutants lacking the neutral phosphatase and distributed among three genetic loci (PD2, PD3, PD24) were investigated for their ability to produce cross-reacting material (CRM) antigenically related to the wild enzyme. All mutants were shown to form much less CRM than the wild-type strain. It is proposed that the three genes are involved in the regulation of neutral phosphatase synthesis.", "contents": "Regulation of the neutral phosphatase in Chlamydomonas reinhardi: an immunogenetic study of wild-type and mutant strains. In Chlamydomonas reinhardi, the activity of the neutral phosphatase considerably increases when the cells are grown in the absence of inorganic phosphate (Pi). A comparative immunological study of cells grown on media containing Pi or not indicated that the neutral phosphatase was synthesized de novo. Ten mutants lacking the neutral phosphatase and distributed among three genetic loci (PD2, PD3, PD24) were investigated for their ability to produce cross-reacting material (CRM) antigenically related to the wild enzyme. All mutants were shown to form much less CRM than the wild-type strain. It is proposed that the three genes are involved in the regulation of neutral phosphatase synthesis."}
{"id": "PMID:203267", "title": "Hydrolysis of synthetic pyrophosphoric esters by an isoenzyme of apyrase from Solanum tuberosum.", "content": "A highly purified isoenzyme of apyrase obtained from potatoes (Solanum tuberosum var. Pimpernel) exhibits a low specificity for the organic moiety of synthetic pyro- and triphosphates. Methyl di- and tri-phosphates were hydrolysed at higher rates than ADP and ATP, but their Km values were also higher. Steric hindrance at the carbon atom linked to the pyrophosphate chain decreases both binding and maximum rate, whereas length or polarity of the organic chain do not have systematic effects. t-Butyl diphosphate, inorganic pyrophosphate, adenosine 5'-[alpha,beta-methylene]triphosphate and adenosine 5'-[beta,gamma-methylene]triphosphate are competitive inhibitors of the hydrolysis of ATP and ADP.", "contents": "Hydrolysis of synthetic pyrophosphoric esters by an isoenzyme of apyrase from Solanum tuberosum. A highly purified isoenzyme of apyrase obtained from potatoes (Solanum tuberosum var. Pimpernel) exhibits a low specificity for the organic moiety of synthetic pyro- and triphosphates. Methyl di- and tri-phosphates were hydrolysed at higher rates than ADP and ATP, but their Km values were also higher. Steric hindrance at the carbon atom linked to the pyrophosphate chain decreases both binding and maximum rate, whereas length or polarity of the organic chain do not have systematic effects. t-Butyl diphosphate, inorganic pyrophosphate, adenosine 5'-[alpha,beta-methylene]triphosphate and adenosine 5'-[beta,gamma-methylene]triphosphate are competitive inhibitors of the hydrolysis of ATP and ADP."}
{"id": "PMID:203268", "title": "Mixed-valence cytochrome oxidase-formate complex. A steady-state intermediate.", "content": "At neutral pH, formate binds to the haem a3 component of cytochrome c oxidase to give a complex that reacts differently from the non-liganded enzyme with reducing agents. Addition of sodium dithionite to the formate complex leads directly to the formation of the fully reduced species, whereas reduction with ascorbate/tetramethylenephenylene-diamine can lead to the production of a mixed-valence species. The stability of this mixed-valence form was studied, and the species appears to represent a 'steady-state' situation that is stable only in the presence of an excess of O2 and reducing equivalents. Characterization of the mixed-valence complex by electron paramagnetic resonance and magnetic circular dichroism reveals the presence of reduced low-spin haem a together with reduced detectable copper and high-spin ferric haem a3.", "contents": "Mixed-valence cytochrome oxidase-formate complex. A steady-state intermediate. At neutral pH, formate binds to the haem a3 component of cytochrome c oxidase to give a complex that reacts differently from the non-liganded enzyme with reducing agents. Addition of sodium dithionite to the formate complex leads directly to the formation of the fully reduced species, whereas reduction with ascorbate/tetramethylenephenylene-diamine can lead to the production of a mixed-valence species. The stability of this mixed-valence form was studied, and the species appears to represent a 'steady-state' situation that is stable only in the presence of an excess of O2 and reducing equivalents. Characterization of the mixed-valence complex by electron paramagnetic resonance and magnetic circular dichroism reveals the presence of reduced low-spin haem a together with reduced detectable copper and high-spin ferric haem a3."}
{"id": "PMID:203293", "title": "Chemotherapeutically active nitro compounds. 4. 5-Nitroimidazoles (Part I).", "content": "More than 135 new 2-methyl-5-nitroimidazoles substituted in 1-position and 1-methyl-5-nitroimidazoles substituted in 2-position were investigated for their activity against various protozoan species, in particular Entamoeba histolytica in the golden hamster, Trichomonas fetus, Trypanosoma brucei and T. cruzi in the NMRI mouse. Among the nitroimidazoles substituted in the 1-position only two preparations exhibited a similar effect as metronidazole preparations exhibited a similar effect as metronidazole against T. fetus. In the class of the nitroimidazoles substituted in the 2-position 16 compounds were as effective as metronidazole, 19 showed an effect superior to metronidazole, 1 was as good as tinidazole and 2 exhibited an activity superior to tinidazole against T. fetus. Only few compounds displayed any amoebicidal activity. Of the mono and bis-hydrazones of 1-methyl-5-nitroimidazole-2-aldehyde substituted in the 2-position 3 compounds had an amoebicidal effect 2 to 8 times stronger than that of metronidazole. Only few representatives of the 1-methyl-5-nitroimidazoles substituted in the 2-position produced a useful trypanocidal effect when given in relatively high doses. The structure-activity relationship of 5-nitroimidazole derivatives has been discussed.", "contents": "Chemotherapeutically active nitro compounds. 4. 5-Nitroimidazoles (Part I). More than 135 new 2-methyl-5-nitroimidazoles substituted in 1-position and 1-methyl-5-nitroimidazoles substituted in 2-position were investigated for their activity against various protozoan species, in particular Entamoeba histolytica in the golden hamster, Trichomonas fetus, Trypanosoma brucei and T. cruzi in the NMRI mouse. Among the nitroimidazoles substituted in the 1-position only two preparations exhibited a similar effect as metronidazole preparations exhibited a similar effect as metronidazole against T. fetus. In the class of the nitroimidazoles substituted in the 2-position 16 compounds were as effective as metronidazole, 19 showed an effect superior to metronidazole, 1 was as good as tinidazole and 2 exhibited an activity superior to tinidazole against T. fetus. Only few compounds displayed any amoebicidal activity. Of the mono and bis-hydrazones of 1-methyl-5-nitroimidazole-2-aldehyde substituted in the 2-position 3 compounds had an amoebicidal effect 2 to 8 times stronger than that of metronidazole. Only few representatives of the 1-methyl-5-nitroimidazoles substituted in the 2-position produced a useful trypanocidal effect when given in relatively high doses. The structure-activity relationship of 5-nitroimidazole derivatives has been discussed."}
{"id": "PMID:203295", "title": "[Diagnosis of Rotavirus using viral RNA electrophoresis].", "content": "Rotavirus has emerged as a major agent of acute enteritis of infants. A rapid and simple technique has been developed for its detection, based on the visualization of the viral RNA electrophoretic pattern. This technique takes advantage of the large amount of rotavirus present in the stools and the high sensitivity for detection of RNA obtained with ethidium bromide.", "contents": "[Diagnosis of Rotavirus using viral RNA electrophoresis]. Rotavirus has emerged as a major agent of acute enteritis of infants. A rapid and simple technique has been developed for its detection, based on the visualization of the viral RNA electrophoretic pattern. This technique takes advantage of the large amount of rotavirus present in the stools and the high sensitivity for detection of RNA obtained with ethidium bromide."}
{"id": "PMID:203294", "title": "[Existence of 2 types of Rotavirus associated with acute gastroenteritis in children].", "content": "Rotaviruses found in the stools of different infants, hospitalized in the Hospital del Ni\u00f1o del DIF, may be grouped into at least two types according to their RNA composition. The viral RNA composition was analyzed by electrophoresis in agarose gels. The different types can be distinguished by the mobility of the second larger of the 11 segments that make up the viral RNA.", "contents": "[Existence of 2 types of Rotavirus associated with acute gastroenteritis in children]. Rotaviruses found in the stools of different infants, hospitalized in the Hospital del Ni\u00f1o del DIF, may be grouped into at least two types according to their RNA composition. The viral RNA composition was analyzed by electrophoresis in agarose gels. The different types can be distinguished by the mobility of the second larger of the 11 segments that make up the viral RNA."}
{"id": "PMID:203306", "title": "Some effects of the aminoglycoside antibiotic amikacin on neuromuscular and autonomic transmission.", "content": "The effects of the new aminoglycoside antibiotic amikacin on neurohumoral transmission were tested in the anaesthetized cat, and in mouse, rat and chick isolated nerve-muscle preparations. Amikacin had blocking actions on both autonomic and neuromuscular transmission. The autonomic effects were caused mainly by ganglion blockade and were reversed by calcium. The amikacin-induced neuromuscular blockade reculted from a decreased release of acetylcholine and a reduced postjunctional sensitivity. Intracellular recording from end-plates in the rat diaphragm demonstrated that amikacin had magnesium-like effects on acetylcholine release. The blockade was reversed completely by calcium, 4-aminopyridine and 3,4-diaminopyridine and partially by neostigmine. The neuromuscular effects of amikacin in vivo were augmented greatly after pretreatment with tubocurarine. It is concluded that care should be exercised if amikacin is administered during surgery in conjunction with tubocurarine.", "contents": "Some effects of the aminoglycoside antibiotic amikacin on neuromuscular and autonomic transmission. The effects of the new aminoglycoside antibiotic amikacin on neurohumoral transmission were tested in the anaesthetized cat, and in mouse, rat and chick isolated nerve-muscle preparations. Amikacin had blocking actions on both autonomic and neuromuscular transmission. The autonomic effects were caused mainly by ganglion blockade and were reversed by calcium. The amikacin-induced neuromuscular blockade reculted from a decreased release of acetylcholine and a reduced postjunctional sensitivity. Intracellular recording from end-plates in the rat diaphragm demonstrated that amikacin had magnesium-like effects on acetylcholine release. The blockade was reversed completely by calcium, 4-aminopyridine and 3,4-diaminopyridine and partially by neostigmine. The neuromuscular effects of amikacin in vivo were augmented greatly after pretreatment with tubocurarine. It is concluded that care should be exercised if amikacin is administered during surgery in conjunction with tubocurarine."}
{"id": "PMID:203307", "title": "Magnitude, dose-requirement and mode of development of tachyphylaxis to suxamethonium in man.", "content": "Tachyphylaxis to suxamethonium infused at a constant rate was studied in 15 surgical patients under enflurane-nitrous oxide-oxygen anaesthesia. The compound electromyographic response of the adductor pollicis muscle to stimulation of the ulnar nerve was monitored. A short-lasting and a long-lasting nearly steady state were observed in Phase I and in Phase II, respectively, during both of which a constant infusion resulted in a constant block. Tachyphylaxis occurred during the transition of phases, beginning after infusion of 1.4 +/- 0.6 (SD) mg kg-1 of suxamethonium, and 36 +/- 14 (SD) minutes of exposure. Tachyphylaxis peaked after 2.6 +/- 1.3 (SD) mg kg-1, and 72 +/- 38 (SD) minutes of exposure. The maximum gain in neuromuscular transmission from the initial maintenance level of block as the result of tachyphylaxis was 53 +/- 24 (SD) % of the control. The results are thought to reconcile previously reported conflicting clinical observations on tachyphylaxis.", "contents": "Magnitude, dose-requirement and mode of development of tachyphylaxis to suxamethonium in man. Tachyphylaxis to suxamethonium infused at a constant rate was studied in 15 surgical patients under enflurane-nitrous oxide-oxygen anaesthesia. The compound electromyographic response of the adductor pollicis muscle to stimulation of the ulnar nerve was monitored. A short-lasting and a long-lasting nearly steady state were observed in Phase I and in Phase II, respectively, during both of which a constant infusion resulted in a constant block. Tachyphylaxis occurred during the transition of phases, beginning after infusion of 1.4 +/- 0.6 (SD) mg kg-1 of suxamethonium, and 36 +/- 14 (SD) minutes of exposure. Tachyphylaxis peaked after 2.6 +/- 1.3 (SD) mg kg-1, and 72 +/- 38 (SD) minutes of exposure. The maximum gain in neuromuscular transmission from the initial maintenance level of block as the result of tachyphylaxis was 53 +/- 24 (SD) % of the control. The results are thought to reconcile previously reported conflicting clinical observations on tachyphylaxis."}
{"id": "PMID:203308", "title": "Attempt to demonstrate an in vivo effect of mianserin hydrochloride on erythrocyte Na+-K+-ATPase activity and cyclic AMP concentration.", "content": "1. There is evidence that erythrocyte Na+-K+-ATPase activity and erythrocyte cyclic AMP change on recovery from a depressive illness. Mianserin is a recently introduced antidepressant but its mode of action is unknown. The present study was therefore designed to investigate in vivo the effect of mianserin on erythrocyte Na+-K+-ATPase and cyclic AMP. 2. Biochemical estimations were made on blood from depressed patients before beginning either mianserin or matched placebo treatment, after 1 week, and again after 2 weeks' treatment. 3. Neither the erythrocyte Na+-K+-ATPase, nor the erythrocyte cyclic AMP concentration, changed significantly in either the mianserin- or the placebo-treated group. 4. The study sheds no light on the possible mechanism of action of mianserin.", "contents": "Attempt to demonstrate an in vivo effect of mianserin hydrochloride on erythrocyte Na+-K+-ATPase activity and cyclic AMP concentration. 1. There is evidence that erythrocyte Na+-K+-ATPase activity and erythrocyte cyclic AMP change on recovery from a depressive illness. Mianserin is a recently introduced antidepressant but its mode of action is unknown. The present study was therefore designed to investigate in vivo the effect of mianserin on erythrocyte Na+-K+-ATPase and cyclic AMP. 2. Biochemical estimations were made on blood from depressed patients before beginning either mianserin or matched placebo treatment, after 1 week, and again after 2 weeks' treatment. 3. Neither the erythrocyte Na+-K+-ATPase, nor the erythrocyte cyclic AMP concentration, changed significantly in either the mianserin- or the placebo-treated group. 4. The study sheds no light on the possible mechanism of action of mianserin."}
{"id": "PMID:203309", "title": "Rheumatoid factor in sera of dermatitis herpetiformis patients.", "content": "Serum specimens from 44 patients with dermatitis herpetiformis (DH) and 42 control patients were analyzed with solid-phase radioimmunoassay (RIA) developed to detect IgG and IgM class antibodies against herpes simplex virus (HSV) envelope antigen. They were also tested with different tests to detect rheumatoid factor (RF) as well as serum antibodies to gastric parietal cells, glomerular basement membrane, smooth muscle, mitochondria and nuclei. Total serum IgG, IgM and IgA quantification was performed concurrently. IgM class antibodies reacting in HSV envelope antigen RIA were found in 47.8% of the DH patients, but in none of the controls. The age distribution of the IgM positive patients was in accordance with the appearance of RF, representing elderly persons. The presence of RF in serum specimens was confirmed by removing the IgM reactivity with heat aggregated human gamma globulin adsorption and in 13 patients with positive serological tests for RF. No correlation was found with the appearance of RF and duration or severity of the disease or with the detection of RF and serum total IgM concentration. In DH patients antibodies to gastric parietal cells were found in 6 and to smooth muscle in 1 of 32 specimens tested.", "contents": "Rheumatoid factor in sera of dermatitis herpetiformis patients. Serum specimens from 44 patients with dermatitis herpetiformis (DH) and 42 control patients were analyzed with solid-phase radioimmunoassay (RIA) developed to detect IgG and IgM class antibodies against herpes simplex virus (HSV) envelope antigen. They were also tested with different tests to detect rheumatoid factor (RF) as well as serum antibodies to gastric parietal cells, glomerular basement membrane, smooth muscle, mitochondria and nuclei. Total serum IgG, IgM and IgA quantification was performed concurrently. IgM class antibodies reacting in HSV envelope antigen RIA were found in 47.8% of the DH patients, but in none of the controls. The age distribution of the IgM positive patients was in accordance with the appearance of RF, representing elderly persons. The presence of RF in serum specimens was confirmed by removing the IgM reactivity with heat aggregated human gamma globulin adsorption and in 13 patients with positive serological tests for RF. No correlation was found with the appearance of RF and duration or severity of the disease or with the detection of RF and serum total IgM concentration. In DH patients antibodies to gastric parietal cells were found in 6 and to smooth muscle in 1 of 32 specimens tested."}
{"id": "PMID:203311", "title": "Mechanisms of microtubule diassembly in vivo: studies in normal and chronic granulomatous disease leucocytes.", "content": "Microtubule assembly in human polmorphonuclear leucocytes is a dynamic process that can be initiated by binding of the plant lectin Concanavalin A to surface receptors. Colchicine inhibits lectin-induced microtubule assembly and promotes the movement of Concanavalin A into surface caps. Inhibition of microtubule assembly and enhanced Concanavalin A cap formation also follow treatment of normal leucocytes with two specific glutathione-oxidizing agents, 'diamide' and tertiary butylhydroperoxide. Our objective here was to determine if microtubule inhibition is mediated via glutathione disulphide or via hydrogen peroxide that is generated in Concanavalin A-treated leucocytes and may accumulate when cells are depleted of reduced glutathione. We show that exogenous hydrogen peroxide induces Concanavalin A capping on normal polymorphonuclear leucocytes but only at concentrations that simultaneously oxidize glutathione. We also show that 'diamide' and tertiary butylhydroperoxide cause Concanavalin A cap formation in leucocytes from patients with chronic granulomatous disease. These cells cannot generate significant amounts of superoxide or hydrogen peroxide. Thus, it seems likely that the reversible inhibition of microtubule assembly and function caused by glutathione oxidants requires only increased glutathione disulphide and is not dependent on subsequent accumulation of other metabolites.", "contents": "Mechanisms of microtubule diassembly in vivo: studies in normal and chronic granulomatous disease leucocytes. Microtubule assembly in human polmorphonuclear leucocytes is a dynamic process that can be initiated by binding of the plant lectin Concanavalin A to surface receptors. Colchicine inhibits lectin-induced microtubule assembly and promotes the movement of Concanavalin A into surface caps. Inhibition of microtubule assembly and enhanced Concanavalin A cap formation also follow treatment of normal leucocytes with two specific glutathione-oxidizing agents, 'diamide' and tertiary butylhydroperoxide. Our objective here was to determine if microtubule inhibition is mediated via glutathione disulphide or via hydrogen peroxide that is generated in Concanavalin A-treated leucocytes and may accumulate when cells are depleted of reduced glutathione. We show that exogenous hydrogen peroxide induces Concanavalin A capping on normal polymorphonuclear leucocytes but only at concentrations that simultaneously oxidize glutathione. We also show that 'diamide' and tertiary butylhydroperoxide cause Concanavalin A cap formation in leucocytes from patients with chronic granulomatous disease. These cells cannot generate significant amounts of superoxide or hydrogen peroxide. Thus, it seems likely that the reversible inhibition of microtubule assembly and function caused by glutathione oxidants requires only increased glutathione disulphide and is not dependent on subsequent accumulation of other metabolites."}
{"id": "PMID:203312", "title": "Impaired neutrophil function and myeloperoxidase deficiency in myeloid metaplasia.", "content": "The ability of neutrophils to phagocytose and kill Candida guilliermondii was investigated in 12 patients with myeloid metaplasia (MM). Following ingestion there was a considerable impairment in the ability of MM neutrophils to kill and digest Candida which was not explained by the very mild impairment in phagocytosis. Quantitative myeloperoxidase measurement revealed an overall deficiency of this enzyme in MM neutrophils and a highly significant correlation between low myeloperoxidase levels and impaired candidacidal activity. Neutrophils from patients with myeloid metaplasia show a pattern of defective microbial killing, high alkaline phosphatase activity and low myeloperoxidase activty which is similar to that seen in severe infections and distinct from chronic granulocytic leukaemia. The cells of one patient with particularly low myeloperoxidase and defective microbial killing were further studied both cytochemically and by electron microscopy. The azurophilic granules of his neutrophils were present in normal numbers and contained normal amounts of acid phosphatase but they lacked myeloperoxidase.", "contents": "Impaired neutrophil function and myeloperoxidase deficiency in myeloid metaplasia. The ability of neutrophils to phagocytose and kill Candida guilliermondii was investigated in 12 patients with myeloid metaplasia (MM). Following ingestion there was a considerable impairment in the ability of MM neutrophils to kill and digest Candida which was not explained by the very mild impairment in phagocytosis. Quantitative myeloperoxidase measurement revealed an overall deficiency of this enzyme in MM neutrophils and a highly significant correlation between low myeloperoxidase levels and impaired candidacidal activity. Neutrophils from patients with myeloid metaplasia show a pattern of defective microbial killing, high alkaline phosphatase activity and low myeloperoxidase activty which is similar to that seen in severe infections and distinct from chronic granulocytic leukaemia. The cells of one patient with particularly low myeloperoxidase and defective microbial killing were further studied both cytochemically and by electron microscopy. The azurophilic granules of his neutrophils were present in normal numbers and contained normal amounts of acid phosphatase but they lacked myeloperoxidase."}
{"id": "PMID:203314", "title": "Association of Pseudomonas cytochrome oxidase with liposomes.", "content": "Purified Pseudomonas cytochrome oxidase has been associated with asolectin liposomes by two different methods. Firstly, the enzyme was attached to liposomic membranes by adding it to a cholate-phospholipid dispersion and subsequently dialyzing the detergent out of suspension. In the second case the enzyme was adsorbed on the preformed liposomes when added to them after the dialysis. A stimulation of the cytochrome oxidase activity approximately twenty-fold was observed by the first method. In contrast, the activation was absent in the second type of preparation, indicating that interaction between the enzyme and phospholipids is very different in the two types of vesicles. The cholate-dialysis method for reconstitution of protein-phospholipid vesicles seems to lead to rather heterogenous preparations. These can be further fractionated, not only according to their size but also to the protein/phospholipid ratio, by gel chromatography.", "contents": "Association of Pseudomonas cytochrome oxidase with liposomes. Purified Pseudomonas cytochrome oxidase has been associated with asolectin liposomes by two different methods. Firstly, the enzyme was attached to liposomic membranes by adding it to a cholate-phospholipid dispersion and subsequently dialyzing the detergent out of suspension. In the second case the enzyme was adsorbed on the preformed liposomes when added to them after the dialysis. A stimulation of the cytochrome oxidase activity approximately twenty-fold was observed by the first method. In contrast, the activation was absent in the second type of preparation, indicating that interaction between the enzyme and phospholipids is very different in the two types of vesicles. The cholate-dialysis method for reconstitution of protein-phospholipid vesicles seems to lead to rather heterogenous preparations. These can be further fractionated, not only according to their size but also to the protein/phospholipid ratio, by gel chromatography."}
{"id": "PMID:203315", "title": "Phospholipid dependence of UDP-glucuronyltransferase.", "content": "Very extensive hydrolysis of phospholipids with pure Bacillus cereus phospholipase C at 5 degrees C greatly inhibited the maximum demonstrable rate of glucuronidation of p-nitrophenol by UDPglucuronyltransferase in guinea pig liver microsomes. Lysophosphatidylcholine restored much of the inhibited activity but non-phospholipid surfactants or hydrolysis of diglycerides failed to reactivate. Phospholipid depletion likewise inhibited o-aminophenol glucuronidation and phospholipids restored activity. It is concluded that glucuronyltransferase specifically requires phospholipids for optimal activity. It seems unlikely that these phospholipids only serve to dissolve aglycones, or that they are direct physiological regulators of the transferase. Instead, a permissive role is ascribed to phospholipids, allowing glucuronyltransferase to be regulated by other means.", "contents": "Phospholipid dependence of UDP-glucuronyltransferase. Very extensive hydrolysis of phospholipids with pure Bacillus cereus phospholipase C at 5 degrees C greatly inhibited the maximum demonstrable rate of glucuronidation of p-nitrophenol by UDPglucuronyltransferase in guinea pig liver microsomes. Lysophosphatidylcholine restored much of the inhibited activity but non-phospholipid surfactants or hydrolysis of diglycerides failed to reactivate. Phospholipid depletion likewise inhibited o-aminophenol glucuronidation and phospholipids restored activity. It is concluded that glucuronyltransferase specifically requires phospholipids for optimal activity. It seems unlikely that these phospholipids only serve to dissolve aglycones, or that they are direct physiological regulators of the transferase. Instead, a permissive role is ascribed to phospholipids, allowing glucuronyltransferase to be regulated by other means."}
{"id": "PMID:203316", "title": "A model for ganglioside behaviour in cell membranes.", "content": "Gangliosides from beef brain have been spin-labeled using two different attaching groups and employed to investigate the physical nature of ganglioside behaviour in membranes. Results obtained using EPR spectroscopy indicate that, in phosphatidylcholine bilayers at physiological pH, ganglioside oligosaccharide chains are quite mobile and show a measurable tendency towards cooperative interaction amongst themselves. We suggest that the source of this interaction is the formation of H-bonds between sugar residues in adjacent ganglioside molecules. We present evidence that physiological (extracellular fluid) levels of Ca2+ and Mg2+ lead to cross-linking and condensing of ganglioside headgroups by complexing sialic acid carboxyl residues. Ganglioside headgroup interactions are not very sensitive to changes in the buffer ionic strength, suggesting that ionic interactions are of minor importance. We have found no measurable tendency for headgroup carbohydrate to penetrate hydrophobic regions of lipid bilayers. EPR spectroscopy was also used to follow the interaction of spin-labeled gangliosides with the glycoprotein, glycophorin, and with intact BHK cells. We suggest that these carbohydrate-based interactions should contribute significantly to the properties of the eucaryotic cell glycocalyx. We predict that laterally mobile carbohydrate-bearing components of cell surface will show a tendency to cluster about complex glycoprotein arrays, especially if the species involved bear accessible carboxylic acid functions.", "contents": "A model for ganglioside behaviour in cell membranes. Gangliosides from beef brain have been spin-labeled using two different attaching groups and employed to investigate the physical nature of ganglioside behaviour in membranes. Results obtained using EPR spectroscopy indicate that, in phosphatidylcholine bilayers at physiological pH, ganglioside oligosaccharide chains are quite mobile and show a measurable tendency towards cooperative interaction amongst themselves. We suggest that the source of this interaction is the formation of H-bonds between sugar residues in adjacent ganglioside molecules. We present evidence that physiological (extracellular fluid) levels of Ca2+ and Mg2+ lead to cross-linking and condensing of ganglioside headgroups by complexing sialic acid carboxyl residues. Ganglioside headgroup interactions are not very sensitive to changes in the buffer ionic strength, suggesting that ionic interactions are of minor importance. We have found no measurable tendency for headgroup carbohydrate to penetrate hydrophobic regions of lipid bilayers. EPR spectroscopy was also used to follow the interaction of spin-labeled gangliosides with the glycoprotein, glycophorin, and with intact BHK cells. We suggest that these carbohydrate-based interactions should contribute significantly to the properties of the eucaryotic cell glycocalyx. We predict that laterally mobile carbohydrate-bearing components of cell surface will show a tendency to cluster about complex glycoprotein arrays, especially if the species involved bear accessible carboxylic acid functions."}
{"id": "PMID:203317", "title": "Regulation of de novo purine biosynthesis in normal and 8-azaguanine-resistant Chinese hamster cells.", "content": "Azaguanine-resistant mutants of Chinese hamster ovary cells were isolated following mutagenesis with ICR-17OG. Of the eight mutant isolates examined, only one, Ag-5 had detectable hypoxanthine(guanine)phosphoribosyltransferase activity. Under normal conditions of growth, de novo purine biosynthesis in the mutants was not significantly different from wild type. However, when the cultures were starved for glutamine over a 2 h period before measuring 5'phosphoribosyl formylglycinamide (a relative measure of de novo purine biosynthesis), elevated levels of 5'-phosphoribosyl formylglycinamide accumulated in some of the mutants, and decreased levels in wild type and Ag-5. The level of purine biosynthesis could be related to the levels of glutamine in the pregrowth medium. The rate of purine biosynthesis correlated with 5-phosphoribosyl pyrophosphate levels, which were enhanced in the mutant (Ag-C) following the starvation period. No alterations were found in levels of 5-phosphoribosyl pyrophosphate synthetase or glutamine synthetase. The extent of feedback inhibition was normal in both mutant and wild type cells. These data suggest that the hypoxanthine (guanine) phosphoribosyltransferase locus is a regulatory gene.", "contents": "Regulation of de novo purine biosynthesis in normal and 8-azaguanine-resistant Chinese hamster cells. Azaguanine-resistant mutants of Chinese hamster ovary cells were isolated following mutagenesis with ICR-17OG. Of the eight mutant isolates examined, only one, Ag-5 had detectable hypoxanthine(guanine)phosphoribosyltransferase activity. Under normal conditions of growth, de novo purine biosynthesis in the mutants was not significantly different from wild type. However, when the cultures were starved for glutamine over a 2 h period before measuring 5'phosphoribosyl formylglycinamide (a relative measure of de novo purine biosynthesis), elevated levels of 5'-phosphoribosyl formylglycinamide accumulated in some of the mutants, and decreased levels in wild type and Ag-5. The level of purine biosynthesis could be related to the levels of glutamine in the pregrowth medium. The rate of purine biosynthesis correlated with 5-phosphoribosyl pyrophosphate levels, which were enhanced in the mutant (Ag-C) following the starvation period. No alterations were found in levels of 5-phosphoribosyl pyrophosphate synthetase or glutamine synthetase. The extent of feedback inhibition was normal in both mutant and wild type cells. These data suggest that the hypoxanthine (guanine) phosphoribosyltransferase locus is a regulatory gene."}
{"id": "PMID:203318", "title": "Phosphorylation of calf thymus RNA polymerase II by nuclear cyclic 3',5'-AMP-independent protein kinase.", "content": "Nucleoplasmic RNA polymerase II (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) from calfthymus is phosphorylated by homologous cyclic AMP-independent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). Polyacrylamide gel electrophoresis of the 32P-labeled RNA polymerase II under non-denaturing conditions revealed that both forms of the enzyme were phosphorylated. Polyacrylamide gel electrophoresis of the 32P-labeled RNA polymerase II under denaturing conditions showed that the 25 000 dalton subunit was the phosphate acceptor subunit. Partial acid hydrolysis of the 32P-labeled RNA polymerase II followed by ion-exchange chromatography revealed serine and threonine as the [32P]phosphate acceptor amino acids. Phosphorylation of the RNA polymerase II was accompanied by a stimulation of enzymatic activity and was dependent upon the presence of ATP.", "contents": "Phosphorylation of calf thymus RNA polymerase II by nuclear cyclic 3',5'-AMP-independent protein kinase. Nucleoplasmic RNA polymerase II (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) from calfthymus is phosphorylated by homologous cyclic AMP-independent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). Polyacrylamide gel electrophoresis of the 32P-labeled RNA polymerase II under non-denaturing conditions revealed that both forms of the enzyme were phosphorylated. Polyacrylamide gel electrophoresis of the 32P-labeled RNA polymerase II under denaturing conditions showed that the 25 000 dalton subunit was the phosphate acceptor subunit. Partial acid hydrolysis of the 32P-labeled RNA polymerase II followed by ion-exchange chromatography revealed serine and threonine as the [32P]phosphate acceptor amino acids. Phosphorylation of the RNA polymerase II was accompanied by a stimulation of enzymatic activity and was dependent upon the presence of ATP."}
{"id": "PMID:203319", "title": "Electrophoretic behaviour of yeast mitochondrial translation products.", "content": "We have studied the mobility of yeast mitochondrial translation products during electrophoresis on polyacrylamide gels of different composition and found that these polypeptides can be divided into two groups. One, to which subunit II of cytochrome c oxidase belongs, behaves normal as all water-soluble reference proteins. The other, to which cytochrome b and subunits I and III of cytochrome c oxidase belong, shows a free electrophoretic mobility about twice as fast as the first group. Conditions have been found to separate cytochrome c1 from cytochrome b.", "contents": "Electrophoretic behaviour of yeast mitochondrial translation products. We have studied the mobility of yeast mitochondrial translation products during electrophoresis on polyacrylamide gels of different composition and found that these polypeptides can be divided into two groups. One, to which subunit II of cytochrome c oxidase belongs, behaves normal as all water-soluble reference proteins. The other, to which cytochrome b and subunits I and III of cytochrome c oxidase belong, shows a free electrophoretic mobility about twice as fast as the first group. Conditions have been found to separate cytochrome c1 from cytochrome b."}
{"id": "PMID:203320", "title": "Inhibition of malate dehydrogenase by thyroxine and structurally related compounds.", "content": "The inhibition of pig heart mitochondrial malate dehydrogenase (L-malate: NAD+ oxidoreductase, EC 1.1.1.37) by the thyroxine and structurally related compounds was studied to resolve a longstanding question about the exact nature of the inhibition. Thyroxine, in freshly prepared solution, was found to be a \"pure\" competitive inhibitor relative to the nucleotide cofactor. Upon standing in diffuse daylight, solutions of thyroxine showed increased ability to inhibit the enzyme, presumably as a result of oxidation of enzyme sulfhydryl groups by free iodine that is released photochemically. This behavior probably accounts for earlier reports of irreversible inactivation by thyroxine. Comment is made on the implications of these findings to the mechanism of thyroid hormmone action.", "contents": "Inhibition of malate dehydrogenase by thyroxine and structurally related compounds. The inhibition of pig heart mitochondrial malate dehydrogenase (L-malate: NAD+ oxidoreductase, EC 1.1.1.37) by the thyroxine and structurally related compounds was studied to resolve a longstanding question about the exact nature of the inhibition. Thyroxine, in freshly prepared solution, was found to be a \"pure\" competitive inhibitor relative to the nucleotide cofactor. Upon standing in diffuse daylight, solutions of thyroxine showed increased ability to inhibit the enzyme, presumably as a result of oxidation of enzyme sulfhydryl groups by free iodine that is released photochemically. This behavior probably accounts for earlier reports of irreversible inactivation by thyroxine. Comment is made on the implications of these findings to the mechanism of thyroid hormmone action."}
{"id": "PMID:203322", "title": "Increased activity of cyclic AMP phosphodiesterase from frozen-thawed rat liver. A role of lysosomal protease in enzyme activation.", "content": "The activity of cyclic AMP phosphodiesterase (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) in 105 000 X g supernatant fraction from frozen-thawed rat liver was 2.5 times higher than the corresponding preparation from fresh liver. This increased activity of frozen liver enzyme was accompanied by a decreased sensitivity of the enzyme to known activators such as alpha-tocopheryl phosphate and trypsin. Neither membrane-bound cyclic AMP phosphodiesterase, nor supernatant cyclic GMP phosphodiesterase increased in frozen liver preparation. It is unlikely that the activator protein of phosphodiesterase participated in the observed change of enzyme activity. Among rat tissues so far tested, the increased level of cyclic AMP phosphodiesterase was noted only in tissues rich in lysosome content. In the recombination experiment where phosphodiesterase from fresh liver was incubated with lysosomal fraction, stimulation of the enzyme activity was observed with a concomitant loss of sensitivity to above-mentioned activators. Since the stimulation by lysosomal fraction was effectively inhibited by cathepsin B1 inhibitors, leupeptin and antipain, it was deduced cathepsin-B1 (EC 3.4.12.3) type protease(s) was the main causative of activating the cyclic AMP phosphodiesterase. The freezing-thawing process of rat liver made the lysosomal membrane more permeable, and hence lysosomal proteases were released into soluble fraction during phosphodiesterase preparation. These results provide a warning not to use frozen liver for phosphodiesterase preparation, otherwise altered properties of the enzymes will be seen.", "contents": "Increased activity of cyclic AMP phosphodiesterase from frozen-thawed rat liver. A role of lysosomal protease in enzyme activation. The activity of cyclic AMP phosphodiesterase (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) in 105 000 X g supernatant fraction from frozen-thawed rat liver was 2.5 times higher than the corresponding preparation from fresh liver. This increased activity of frozen liver enzyme was accompanied by a decreased sensitivity of the enzyme to known activators such as alpha-tocopheryl phosphate and trypsin. Neither membrane-bound cyclic AMP phosphodiesterase, nor supernatant cyclic GMP phosphodiesterase increased in frozen liver preparation. It is unlikely that the activator protein of phosphodiesterase participated in the observed change of enzyme activity. Among rat tissues so far tested, the increased level of cyclic AMP phosphodiesterase was noted only in tissues rich in lysosome content. In the recombination experiment where phosphodiesterase from fresh liver was incubated with lysosomal fraction, stimulation of the enzyme activity was observed with a concomitant loss of sensitivity to above-mentioned activators. Since the stimulation by lysosomal fraction was effectively inhibited by cathepsin B1 inhibitors, leupeptin and antipain, it was deduced cathepsin-B1 (EC 3.4.12.3) type protease(s) was the main causative of activating the cyclic AMP phosphodiesterase. The freezing-thawing process of rat liver made the lysosomal membrane more permeable, and hence lysosomal proteases were released into soluble fraction during phosphodiesterase preparation. These results provide a warning not to use frozen liver for phosphodiesterase preparation, otherwise altered properties of the enzymes will be seen."}
{"id": "PMID:203323", "title": "The catabolism of human and rat very low density lipoproteins by perfused rat hearts.", "content": "The catabolism of human and rat 125I-labelled very low density lipoproteins (VLDL) was compared by perfusing the lipoproteins through beating rat hearts. Triacylglycerol was removed from the VLDL to a greater extent than the protein moiety, leaving remnants containing relatively more apo-B and less apo-C. The change in apo-C content of the remnants correlated with the loss of triacylglycerol. The extent of removal of triacylglycerol from the rat and human VLDL was similar and in most cases appeared to saturate the heart lipoprotein lipase. The remnants were slightly smaller in size than the VLDL, and included particles which appeared to be partially emptied. In addition to remnants of d less than 1.019 g/ml, iodinated lipoproteins derived from rat and human VLDL were recovered at d 1.019-1.063 and 1.063-1.21 g/ml. The former contained largely cholesterol and cholesteryl esters, while phospholipids were the dominant lipid in the latter. An average of 40% of the 125I-labelled apoprotein lost from the VLDL was associated with the perfused hearts. Very little d 1.019-1.063 g/ml lipoprotein was produced from low (physiological) concentrations of rat VLDL, most of the lipoprotein being removed by the heart. However, lipoproteins of density 1.019-1.063 g/ml were formed from human VLDL at all concentrations in the perfusate, as well as from higher concentrations of the rat VLDL. Agarose gel filtration of lipoproteins following heart perfusion with human VLDL revealed large aggregates containing particles which resemble low density lipoproteins (LDL) in electron microscopic appearance and apoprotein composition, since they contain largely apo-B. These data suggest that at normal concentrations rat VLDL are almost completely catabolised and taken up by the heart without the formation of LDL, while LDL is produced from human VLDL at all concentrations.", "contents": "The catabolism of human and rat very low density lipoproteins by perfused rat hearts. The catabolism of human and rat 125I-labelled very low density lipoproteins (VLDL) was compared by perfusing the lipoproteins through beating rat hearts. Triacylglycerol was removed from the VLDL to a greater extent than the protein moiety, leaving remnants containing relatively more apo-B and less apo-C. The change in apo-C content of the remnants correlated with the loss of triacylglycerol. The extent of removal of triacylglycerol from the rat and human VLDL was similar and in most cases appeared to saturate the heart lipoprotein lipase. The remnants were slightly smaller in size than the VLDL, and included particles which appeared to be partially emptied. In addition to remnants of d less than 1.019 g/ml, iodinated lipoproteins derived from rat and human VLDL were recovered at d 1.019-1.063 and 1.063-1.21 g/ml. The former contained largely cholesterol and cholesteryl esters, while phospholipids were the dominant lipid in the latter. An average of 40% of the 125I-labelled apoprotein lost from the VLDL was associated with the perfused hearts. Very little d 1.019-1.063 g/ml lipoprotein was produced from low (physiological) concentrations of rat VLDL, most of the lipoprotein being removed by the heart. However, lipoproteins of density 1.019-1.063 g/ml were formed from human VLDL at all concentrations in the perfusate, as well as from higher concentrations of the rat VLDL. Agarose gel filtration of lipoproteins following heart perfusion with human VLDL revealed large aggregates containing particles which resemble low density lipoproteins (LDL) in electron microscopic appearance and apoprotein composition, since they contain largely apo-B. These data suggest that at normal concentrations rat VLDL are almost completely catabolised and taken up by the heart without the formation of LDL, while LDL is produced from human VLDL at all concentrations."}
{"id": "PMID:203324", "title": "Catabolism of very low density lipoproteins in the rabbit. Effect of changing composition and pool size.", "content": "To determine the metabolic mechanism of hypercholesterolemia in rabbits produced by feeding cholesterol-rich diets, control and hypercholesterolemic rabbits were injected with I-labelled very low density lipoproteins (VLDL, d 1.006 g/ml) from control and/or hypercholesterolemic donors. Apolipoprotein B in VLDL decayed biphasically. The first phase occurred much more rapid than the second. 95% of the VLDL apolipoprotein B was catabolized via the first phase (t1/2 = 0.55 +/- 0.19 h) in normal rabbit with the immediate appearance of this radioactivity in intermediate density lipoproteins (IDL, d 1.006-1.025 g/ml) and low density lipoproteins (LDL, d 1.025-1.063 g/ml). The apolipoproteins C and E at the same time were transferred to high density lipoproteins where they decayed biphasically. The apolipoprotein B from hypercholesterolemic VLDL in the normal recipient disappeared at a similar rate as from normal VLDL via phase I; however, it was incompletely converted to IDL and LDL. Apolipoprotein B from normal VLDL in cholesterol-fed rabbits disappeared at a normal rate via phase I, but only 82% was catabolized by this phase. Hypercholesterolemic VLDL injected into the hypercholesterolemic recipient was less rapidly catabolized via phase I (T1/2 = 2.5 +/- 0.89 H) and only a small fraction was converted to IDL and LDL.", "contents": "Catabolism of very low density lipoproteins in the rabbit. Effect of changing composition and pool size. To determine the metabolic mechanism of hypercholesterolemia in rabbits produced by feeding cholesterol-rich diets, control and hypercholesterolemic rabbits were injected with I-labelled very low density lipoproteins (VLDL, d 1.006 g/ml) from control and/or hypercholesterolemic donors. Apolipoprotein B in VLDL decayed biphasically. The first phase occurred much more rapid than the second. 95% of the VLDL apolipoprotein B was catabolized via the first phase (t1/2 = 0.55 +/- 0.19 h) in normal rabbit with the immediate appearance of this radioactivity in intermediate density lipoproteins (IDL, d 1.006-1.025 g/ml) and low density lipoproteins (LDL, d 1.025-1.063 g/ml). The apolipoproteins C and E at the same time were transferred to high density lipoproteins where they decayed biphasically. The apolipoprotein B from hypercholesterolemic VLDL in the normal recipient disappeared at a similar rate as from normal VLDL via phase I; however, it was incompletely converted to IDL and LDL. Apolipoprotein B from normal VLDL in cholesterol-fed rabbits disappeared at a normal rate via phase I, but only 82% was catabolized by this phase. Hypercholesterolemic VLDL injected into the hypercholesterolemic recipient was less rapidly catabolized via phase I (T1/2 = 2.5 +/- 0.89 H) and only a small fraction was converted to IDL and LDL."}
{"id": "PMID:203325", "title": "Interactions of native and modified human low density lipoproteins with human skin fibroblasts.", "content": "125I-labeled low density lipoprotein (LDL) covalently bonded to Sepharose beads was not degraded by normal human fibroblasts nor did it trigger inhibition of sterol synthesis. The Sepharose beads loaded with LDL bound very tightly to the surface both of normal fibroblasts and fibroblasts from a subject with homozygous familial hypercholesterolemia; control Sepharose beads (activated sites covered with glycine) did not adhere to either cell type. LDL was extracted by a modification of the method of Gustafson (Gustafson, A. (1965) J. Lipid Res. 6, 512-517), so as to remove essentially all cholesterol, cholesterol ester and triglyceride. This modified LDL was bound, internalized and degraded as well as or better than native LDL. However, it failed to suppress sterol synthesis. These results provide additional evidence that the sterol moiety of the LDL is the key component affecting sterol synthesis. They also imply that the neutral lipids of LDL play a minor role in the binding of LDL to cell membranes and that the apoprotein rather than molecular size and shape is the critical factor.", "contents": "Interactions of native and modified human low density lipoproteins with human skin fibroblasts. 125I-labeled low density lipoprotein (LDL) covalently bonded to Sepharose beads was not degraded by normal human fibroblasts nor did it trigger inhibition of sterol synthesis. The Sepharose beads loaded with LDL bound very tightly to the surface both of normal fibroblasts and fibroblasts from a subject with homozygous familial hypercholesterolemia; control Sepharose beads (activated sites covered with glycine) did not adhere to either cell type. LDL was extracted by a modification of the method of Gustafson (Gustafson, A. (1965) J. Lipid Res. 6, 512-517), so as to remove essentially all cholesterol, cholesterol ester and triglyceride. This modified LDL was bound, internalized and degraded as well as or better than native LDL. However, it failed to suppress sterol synthesis. These results provide additional evidence that the sterol moiety of the LDL is the key component affecting sterol synthesis. They also imply that the neutral lipids of LDL play a minor role in the binding of LDL to cell membranes and that the apoprotein rather than molecular size and shape is the critical factor."}
{"id": "PMID:203327", "title": "Biochemical composition and heterogeneity of heparan sulfates isolated from AH-130 ascites hepatoma cells and fluid.", "content": "The glycosaminoglycan composition of AH-130 ascites hepatoma cells and fluid were examined using enzymatic digestion, electrophoresis, and sequential partition fractionation. The cell-associated glycosaminoglycans were found to consist of 93% heparan sulfate, with the remainder consisting primarily of chondroitin sulfate. The glycosaminoglycans isolated from the ascitic fluid were found to consist of 58% heparan sulfate, 26% hyaluronic acid and 16% chondroitin sulfate. Dermatan sulfate was not detected in either cells or fluid. The heparan sulfate isolated from AH-130 cells in low-sulfate and highly heterogeneous with respect to biochemical composition. Fractions isolated by partition fractionation varied from 0.14 mol sulfate/mol uronic acid to 0.6 mol sulfate/mol uronic acid. Of the total sulfate 70--80% is N-sulfate in the former and 50% in the latter. Electrophoresis in 0.1 M HCl showed a highly heterogeneous material with mobility between that of hyaluronic acid and beef lung heparan sulfate. The heparan sulfate isolated from the fluid was similar to that isolated from the cells but was, however, somewhat more homogeneous with respect to charge.", "contents": "Biochemical composition and heterogeneity of heparan sulfates isolated from AH-130 ascites hepatoma cells and fluid. The glycosaminoglycan composition of AH-130 ascites hepatoma cells and fluid were examined using enzymatic digestion, electrophoresis, and sequential partition fractionation. The cell-associated glycosaminoglycans were found to consist of 93% heparan sulfate, with the remainder consisting primarily of chondroitin sulfate. The glycosaminoglycans isolated from the ascitic fluid were found to consist of 58% heparan sulfate, 26% hyaluronic acid and 16% chondroitin sulfate. Dermatan sulfate was not detected in either cells or fluid. The heparan sulfate isolated from AH-130 cells in low-sulfate and highly heterogeneous with respect to biochemical composition. Fractions isolated by partition fractionation varied from 0.14 mol sulfate/mol uronic acid to 0.6 mol sulfate/mol uronic acid. Of the total sulfate 70--80% is N-sulfate in the former and 50% in the latter. Electrophoresis in 0.1 M HCl showed a highly heterogeneous material with mobility between that of hyaluronic acid and beef lung heparan sulfate. The heparan sulfate isolated from the fluid was similar to that isolated from the cells but was, however, somewhat more homogeneous with respect to charge."}
{"id": "PMID:203328", "title": "Two types of cyclic GMP binding site associated with the cyclic AMP-dependent protein kinase from lymphocytes.", "content": "Low- and high-affinity binding sites for cyclic GMP were found to be associated with the cyclic AMP-dependent protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) from human tonsillar lymphocytes, but neither of them was identical with the cyclic AMP binding site. The enzyme activated by cyclic GMP phosphorylated the same site of calf thymus H2b histone as the cyclic AMP activated enzyme; however, more complex kinetics of activation were found with cyclic GMP. Two classes of cyclic GMP binding site were demonstrated by kinetic analysis of cyclic [3H]GMP binding in the enzyme preparations eluted by 0.1 M potassium phosphate (pH 7.0) from DEAE cellulose. The high-affinity cyclic GMP binding site (Kd about 4 . 10(-8) M) belonged to some complex form of the protein kinase, as evidenced by the mutual inhibition of cyclic AMP binding and high affinity cyclic GMP binding. However, the high-affinity cyclic GMP binding site disappeared on Sephadex G-100 gel chromatography of the enzyme preparation, whereas the cyclic AMP binding activity was recovered quantitively as separate fractions. The low-affinity cyclic GMP binding site (Kd 2--5 . 10(-6) M) was demonstrated by the inhibitory effect of 10(-5) M cyclic GMP on cyclic AMP binding in each cyclic AMP binding fraction obtained by gel chromatography. However, cyclic AMP did not inhibit the binding of cyclic GMP to the low-affinity binding site.", "contents": "Two types of cyclic GMP binding site associated with the cyclic AMP-dependent protein kinase from lymphocytes. Low- and high-affinity binding sites for cyclic GMP were found to be associated with the cyclic AMP-dependent protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) from human tonsillar lymphocytes, but neither of them was identical with the cyclic AMP binding site. The enzyme activated by cyclic GMP phosphorylated the same site of calf thymus H2b histone as the cyclic AMP activated enzyme; however, more complex kinetics of activation were found with cyclic GMP. Two classes of cyclic GMP binding site were demonstrated by kinetic analysis of cyclic [3H]GMP binding in the enzyme preparations eluted by 0.1 M potassium phosphate (pH 7.0) from DEAE cellulose. The high-affinity cyclic GMP binding site (Kd about 4 . 10(-8) M) belonged to some complex form of the protein kinase, as evidenced by the mutual inhibition of cyclic AMP binding and high affinity cyclic GMP binding. However, the high-affinity cyclic GMP binding site disappeared on Sephadex G-100 gel chromatography of the enzyme preparation, whereas the cyclic AMP binding activity was recovered quantitively as separate fractions. The low-affinity cyclic GMP binding site (Kd 2--5 . 10(-6) M) was demonstrated by the inhibitory effect of 10(-5) M cyclic GMP on cyclic AMP binding in each cyclic AMP binding fraction obtained by gel chromatography. However, cyclic AMP did not inhibit the binding of cyclic GMP to the low-affinity binding site."}
{"id": "PMID:203329", "title": "Conformation of L-cystathionine, a carba analog of cystine, and stereochemistry of hormone-receptor interactions.", "content": "The conformation of L-cystathionine, a carba analog of L-cystine, has been studied in the solid state using X-ray diffraction techniques. Crystal of L-cystathionine are tetragonal, space group P41 with cell constants a = 6.691(1) A, c = 21.998(3) A and Z = 4. From diffractometer data to the limit of 2theta = 162 degrees for Cukalpha, the structure was refined using full-matrix least-squares to an R value of 0.061. L-Cystathionine is isostructural chemically to L-cystine and its crystal structure is isomorphous to tetragonal L-cystine (Chaney, M.O. and Steinrauf, L.K. (1974) Acta Crystallogr. 1330, 711--716). The crystal structure of L-cystathionine is disordered, leading to two slightly differing conformers of L-cystathionine (each with half occupancy) with same helical sense but running in opposite directions and occupying the locations of L-cystine molecules in tetragonal L-cystine structure. Their conformational similarity, even when no sterical constraints such as cyclization are present, offers an explanation of the activities of the carba analogs of neuro-hypophysial hormones in terms of the structural integrity of the disulfide-like bridges.", "contents": "Conformation of L-cystathionine, a carba analog of cystine, and stereochemistry of hormone-receptor interactions. The conformation of L-cystathionine, a carba analog of L-cystine, has been studied in the solid state using X-ray diffraction techniques. Crystal of L-cystathionine are tetragonal, space group P41 with cell constants a = 6.691(1) A, c = 21.998(3) A and Z = 4. From diffractometer data to the limit of 2theta = 162 degrees for Cukalpha, the structure was refined using full-matrix least-squares to an R value of 0.061. L-Cystathionine is isostructural chemically to L-cystine and its crystal structure is isomorphous to tetragonal L-cystine (Chaney, M.O. and Steinrauf, L.K. (1974) Acta Crystallogr. 1330, 711--716). The crystal structure of L-cystathionine is disordered, leading to two slightly differing conformers of L-cystathionine (each with half occupancy) with same helical sense but running in opposite directions and occupying the locations of L-cystine molecules in tetragonal L-cystine structure. Their conformational similarity, even when no sterical constraints such as cyclization are present, offers an explanation of the activities of the carba analogs of neuro-hypophysial hormones in terms of the structural integrity of the disulfide-like bridges."}
{"id": "PMID:203331", "title": "Noninactivation of thyrotropin by cultured porcine thyroid cells.", "content": "Freshly isolated porcine thyroid cells were cultured in the presence of highly purified porcine thyrotropin. Cells associate into follicles between the second and tenth day of culture and later form a monolayer. The biological and immunological activity of thyrotropin was measured daily in the media. Thyrotropin concentration and biological activity remained unchanged from the onset of the culture up to day 14. Limiting factors influencing thyroglobulin biosynthesis do not appear before day 13. The loss of follicular organization at day 10 cannot be explained by thyrotropin degradation in the medium. Considering the number of receptors per cell and the half life of the thyrotropin . receptor complex in the two dissociation compartments previously demonstrated, it appears in terms of both biological activity and affinity for the receptors that the thyrotropin molecules released from the first compartment do not differ from native molecules. It can be calculated that at least 31% of the molecules released from the second compartment are not inactivated. Thus, it is probable that the catabolism of thyrotropin on the receptor, or near the receptor site, does not play an important role in the regulation of thyroid cell function in vitro.", "contents": "Noninactivation of thyrotropin by cultured porcine thyroid cells. Freshly isolated porcine thyroid cells were cultured in the presence of highly purified porcine thyrotropin. Cells associate into follicles between the second and tenth day of culture and later form a monolayer. The biological and immunological activity of thyrotropin was measured daily in the media. Thyrotropin concentration and biological activity remained unchanged from the onset of the culture up to day 14. Limiting factors influencing thyroglobulin biosynthesis do not appear before day 13. The loss of follicular organization at day 10 cannot be explained by thyrotropin degradation in the medium. Considering the number of receptors per cell and the half life of the thyrotropin . receptor complex in the two dissociation compartments previously demonstrated, it appears in terms of both biological activity and affinity for the receptors that the thyrotropin molecules released from the first compartment do not differ from native molecules. It can be calculated that at least 31% of the molecules released from the second compartment are not inactivated. Thus, it is probable that the catabolism of thyrotropin on the receptor, or near the receptor site, does not play an important role in the regulation of thyroid cell function in vitro."}
{"id": "PMID:203332", "title": "Mitogenic andadjuvant activities of polysaccharides from the cellular slime mold, Dictyostelium discoideum NC-4.", "content": "Cell surface and extracellular polysaccharide fractions obtained from Dictyostelium discoideum NC-4 cultured in bacteria-free medium showed strong B-cell mitogenic activities. Upon periodate treatment of the extra-cellular polysaccharide fraction this activity completely disappeared. The extracellular polysaccharide fraction could also enhance the antibody response in vitro against sheep red blood cells.", "contents": "Mitogenic andadjuvant activities of polysaccharides from the cellular slime mold, Dictyostelium discoideum NC-4. Cell surface and extracellular polysaccharide fractions obtained from Dictyostelium discoideum NC-4 cultured in bacteria-free medium showed strong B-cell mitogenic activities. Upon periodate treatment of the extra-cellular polysaccharide fraction this activity completely disappeared. The extracellular polysaccharide fraction could also enhance the antibody response in vitro against sheep red blood cells."}
{"id": "PMID:203333", "title": "Beta-adrenergic receptors and adenylate cyclase in hypertrophic and hyperplastic rat salivary glands.", "content": "Isoproterenol induces both the secretion of protein and the stimulation of DNA synthesis and growth in rat salivary glands. The specific binding of the labelled beta-adrenergic antagonist [3H]dihydroalprenolol has been used to measure the number of beta-adrenergic receptors in rat parotid glands during isoproterenol-induced growth. Isoproterenol-enlarged glands display no change in the specific binding capacity per gland for [3H]-dihydroalprenolol compared with normal tissue. Catecholamine sensitive adenylate cyclase activity varies independently of the number of specific [3H]dihydroalprenolol binding sites during isoproterenol-induced growth. Previously-described di-ferences in optimal isoproterenol doses which produce protein secretion and stimulation of DNA synthesis may reflect different responses to various rates of receptor occupancy, or may be due to the presence of more than one type of beta-adrenergic receptor.", "contents": "Beta-adrenergic receptors and adenylate cyclase in hypertrophic and hyperplastic rat salivary glands. Isoproterenol induces both the secretion of protein and the stimulation of DNA synthesis and growth in rat salivary glands. The specific binding of the labelled beta-adrenergic antagonist [3H]dihydroalprenolol has been used to measure the number of beta-adrenergic receptors in rat parotid glands during isoproterenol-induced growth. Isoproterenol-enlarged glands display no change in the specific binding capacity per gland for [3H]-dihydroalprenolol compared with normal tissue. Catecholamine sensitive adenylate cyclase activity varies independently of the number of specific [3H]dihydroalprenolol binding sites during isoproterenol-induced growth. Previously-described di-ferences in optimal isoproterenol doses which produce protein secretion and stimulation of DNA synthesis may reflect different responses to various rates of receptor occupancy, or may be due to the presence of more than one type of beta-adrenergic receptor."}
{"id": "PMID:203338", "title": "[Inhibition of the yeast respiratory system by Zn-protoporphyrin and effect of photolysis of this substance].", "content": "We have shown earlier that yeast cells grown in synthetic mediums supplemented with Zn++ accumulate large amounts of Zn-protoporphyrin within their mitochondria. This accumulation is accompanied by an inhibition of respiration (3). This study deals with the effect of light on the respiratory inhibition and the release of respiratory control which are observed if Zn-protoporphyrin is added to isolated mitochondria which are initially devoid of this pigment. In addition, we have studied the effect of light on the respiratory inhibition exerted by Zn-protoporphyrin accumulated in vivo. The following results were obtained: 1) The light-induced destruction of Zn-protoporphrin which had been added in vitro to Zn-protoporphyrin-free mitochondria significantly inhibits respiration and phosphorylation. Under these conditions, the extent of the inhibitions increases with the concentration of the added Zn-protoporphyrin and the duration of illumination. 2) Accumulation of Zn-protoporphyrin within the cells causes an inhibition of the respiratory activities and the activities of succinate-cytochrome c reductase and NADH-cytochrome c reductase of the mitochondria. Illumination of the isolated mitochondria from Zn-protoporphyrin-containing cells enhances the inhibition of these activities. No light-induced inhibition of these activities is observed with mitochondria from cells devoid of Zn-protoporphyrin.", "contents": "[Inhibition of the yeast respiratory system by Zn-protoporphyrin and effect of photolysis of this substance]. We have shown earlier that yeast cells grown in synthetic mediums supplemented with Zn++ accumulate large amounts of Zn-protoporphyrin within their mitochondria. This accumulation is accompanied by an inhibition of respiration (3). This study deals with the effect of light on the respiratory inhibition and the release of respiratory control which are observed if Zn-protoporphyrin is added to isolated mitochondria which are initially devoid of this pigment. In addition, we have studied the effect of light on the respiratory inhibition exerted by Zn-protoporphyrin accumulated in vivo. The following results were obtained: 1) The light-induced destruction of Zn-protoporphrin which had been added in vitro to Zn-protoporphyrin-free mitochondria significantly inhibits respiration and phosphorylation. Under these conditions, the extent of the inhibitions increases with the concentration of the added Zn-protoporphyrin and the duration of illumination. 2) Accumulation of Zn-protoporphyrin within the cells causes an inhibition of the respiratory activities and the activities of succinate-cytochrome c reductase and NADH-cytochrome c reductase of the mitochondria. Illumination of the isolated mitochondria from Zn-protoporphyrin-containing cells enhances the inhibition of these activities. No light-induced inhibition of these activities is observed with mitochondria from cells devoid of Zn-protoporphyrin."}
{"id": "PMID:203339", "title": "[Origin and fixation of pyrophosphates in the parietal bones of young rats].", "content": "Calvaria from 6 to 13-day-old rats mineralize and bind pyrophosphates which are transferred from nucleotides, as shown by : 1 -- the increase of pyrophosphates in young rat calvaria incubated with nucleoside triphosphate, especially ATP ; 2 -- the more important increase of pyrophosphate content when ATP is renewed in the incubation medium ; and 3 -- binding of [32P] pyrophosphate [beta 32P] ATP. The effect of preheating of calvaria on 32P binding from [beta32P]ATP led us to assume that two systems might be involved in pyrophosphate fixation : a heat-labile, non-specific, phosphatase system, and a heat-stable pyrophosphotransferase system. cAMP increases the pyrophosphate content of calvaria incubated with ATP : that effect may result from either an inhibition of the phosphatase system, or an activation of the pyrophosphotransferase system.", "contents": "[Origin and fixation of pyrophosphates in the parietal bones of young rats]. Calvaria from 6 to 13-day-old rats mineralize and bind pyrophosphates which are transferred from nucleotides, as shown by : 1 -- the increase of pyrophosphates in young rat calvaria incubated with nucleoside triphosphate, especially ATP ; 2 -- the more important increase of pyrophosphate content when ATP is renewed in the incubation medium ; and 3 -- binding of [32P] pyrophosphate [beta 32P] ATP. The effect of preheating of calvaria on 32P binding from [beta32P]ATP led us to assume that two systems might be involved in pyrophosphate fixation : a heat-labile, non-specific, phosphatase system, and a heat-stable pyrophosphotransferase system. cAMP increases the pyrophosphate content of calvaria incubated with ATP : that effect may result from either an inhibition of the phosphatase system, or an activation of the pyrophosphotransferase system."}
{"id": "PMID:203335", "title": "[Registration of the Opaque-2 mutation by the EPR method].", "content": "The ESR method shows that variation of lysin concentration in the maiz enzyme resulting from the Opaque-2 mutation correlates with the number of paramagnetic centres in seed fractions. Increase of the lysin concentration brings about a quick rise of the ESR amplitude in the enzyme fraction of aleyrone layer and a decrease of the ESR amplitude in the seed germ.", "contents": "[Registration of the Opaque-2 mutation by the EPR method]. The ESR method shows that variation of lysin concentration in the maiz enzyme resulting from the Opaque-2 mutation correlates with the number of paramagnetic centres in seed fractions. Increase of the lysin concentration brings about a quick rise of the ESR amplitude in the enzyme fraction of aleyrone layer and a decrease of the ESR amplitude in the seed germ."}
{"id": "PMID:203334", "title": "[Model of a neuron-regulator of the effectiveness of synaptic transmission].", "content": "In diad and triad synapses of vertebrate retina the transmitter released from one and the same presynaptic membrane can act simultaneously on two (or even three) postsynaptic neurones. The model of such a diad synapse is proposed, in which the positive electrical feed-back is caried out between one of postsynaptic and presynaptic neurones. The feed-back appears because of potential drop across the longitudinal resistance of intercellular gap (RIII) near the activated synapse (see [1]). It is shown that if the input resistance of this postsynaptic neurone (N3) is low (low R3 in fig. 1,), it can operate as a regulator of effectiveness of synaptic transmission between the presynaptic (N1) and the second postsynaptic (N2) neurones. The effectiveness of synpatic transmission (e. g. the steepness of transfer function) is the more, the higher the membrane potential in the neurone acting as a regulator (fig. 2), and the higher the resistance of intercellular gap (RIII) (fig. 2). The model reproduces the effect of polarization of horizontal cells (by means of light or current) on the membrane potential in bipolars of the turtle and fish retina (fig. 3). The analysis of the model also shows that one of the functions of horizontal cells, as regulators of synaptic transmission between photoreceptors and bipolars, may be the detection of small objects and borders of image against uniform background.", "contents": "[Model of a neuron-regulator of the effectiveness of synaptic transmission]. In diad and triad synapses of vertebrate retina the transmitter released from one and the same presynaptic membrane can act simultaneously on two (or even three) postsynaptic neurones. The model of such a diad synapse is proposed, in which the positive electrical feed-back is caried out between one of postsynaptic and presynaptic neurones. The feed-back appears because of potential drop across the longitudinal resistance of intercellular gap (RIII) near the activated synapse (see [1]). It is shown that if the input resistance of this postsynaptic neurone (N3) is low (low R3 in fig. 1,), it can operate as a regulator of effectiveness of synaptic transmission between the presynaptic (N1) and the second postsynaptic (N2) neurones. The effectiveness of synpatic transmission (e. g. the steepness of transfer function) is the more, the higher the membrane potential in the neurone acting as a regulator (fig. 2), and the higher the resistance of intercellular gap (RIII) (fig. 2). The model reproduces the effect of polarization of horizontal cells (by means of light or current) on the membrane potential in bipolars of the turtle and fish retina (fig. 3). The analysis of the model also shows that one of the functions of horizontal cells, as regulators of synaptic transmission between photoreceptors and bipolars, may be the detection of small objects and borders of image against uniform background."}
{"id": "PMID:203340", "title": "[Mechanism of action of cyclic AMP-dependent histone kinase. Substrate specificity of the catalytic enzyme unit].", "content": "Interaction of several nucleotide derivates with homogenous catalytic subunit of cyclo-AMP-dependent histone kinase from pig brain is studied. Inhibition constants of these compounds are calculated, and the affinity of inhibitors to the enzyme active site is evaluated. The nature of heterocyclic base is found to be the main contribution into binding with substrate. The enzyme specificity with respect to a number of bivalent metal ions is studied, and Mg2+ is demonstrated to be the only efficient enzyme activator. It is shown by means of stationary kinetics that histone kinase-catalysed phosphotransferase reaction has a \"ping-pong\"-like mechanism.", "contents": "[Mechanism of action of cyclic AMP-dependent histone kinase. Substrate specificity of the catalytic enzyme unit]. Interaction of several nucleotide derivates with homogenous catalytic subunit of cyclo-AMP-dependent histone kinase from pig brain is studied. Inhibition constants of these compounds are calculated, and the affinity of inhibitors to the enzyme active site is evaluated. The nature of heterocyclic base is found to be the main contribution into binding with substrate. The enzyme specificity with respect to a number of bivalent metal ions is studied, and Mg2+ is demonstrated to be the only efficient enzyme activator. It is shown by means of stationary kinetics that histone kinase-catalysed phosphotransferase reaction has a \"ping-pong\"-like mechanism."}
{"id": "PMID:203341", "title": "[Effect of a single ethanol injection on lipid and lipoprotein synthesis in rat liver].", "content": "A single ethanol injection results in the increase of mono-, di- and tri-glicerides synthesis in rat liver, and also of the synthesis of apoprotein of very low density lipoproteins, their formation and secretion. Different uptake of pools of 14C-acetyl CoA, synthesized from injected 14C-acetate, and 3H-acetyl CoA, synthesized through metabolic pathways of 3H-leucine, indicates the compartmentalization of acetyl CoA in the synthesis of saturated and unsaturated fatty acids. 3H-acetyl CoA is more intensively used in the synthesis of unsaturated fatty acids than 14C-acetyl CoA synthesized from acetate. Ethanol increases the uptake of acetyl CoA, synthesized from acetate, for the synthesis of all the lipids, probably, for the expense of the increased synthesis of endogenous acetate in metabolic transformation of ethanol.", "contents": "[Effect of a single ethanol injection on lipid and lipoprotein synthesis in rat liver]. A single ethanol injection results in the increase of mono-, di- and tri-glicerides synthesis in rat liver, and also of the synthesis of apoprotein of very low density lipoproteins, their formation and secretion. Different uptake of pools of 14C-acetyl CoA, synthesized from injected 14C-acetate, and 3H-acetyl CoA, synthesized through metabolic pathways of 3H-leucine, indicates the compartmentalization of acetyl CoA in the synthesis of saturated and unsaturated fatty acids. 3H-acetyl CoA is more intensively used in the synthesis of unsaturated fatty acids than 14C-acetyl CoA synthesized from acetate. Ethanol increases the uptake of acetyl CoA, synthesized from acetate, for the synthesis of all the lipids, probably, for the expense of the increased synthesis of endogenous acetate in metabolic transformation of ethanol."}
{"id": "PMID:203336", "title": "[Bioenergetics and proton-electron membrane systems].", "content": "Measurements of potential difference on energy producing subcellular particles by the methods of penetrating ions and of association of these particles with the planar membrane are described as well as some other studies of cell electrical energetics in which the author took part.", "contents": "[Bioenergetics and proton-electron membrane systems]. Measurements of potential difference on energy producing subcellular particles by the methods of penetrating ions and of association of these particles with the planar membrane are described as well as some other studies of cell electrical energetics in which the author took part."}
{"id": "PMID:203342", "title": "[Separation of catalytic and regulatory subunits of pigeon breast muscle protein kinase].", "content": "The separation of catalytic cAMP-independent and regulatory cAMP-binding subunits of pigeon breast muscle protein kinase was performed after the treatment of the holoenzyme by cAMP. The molecular weight of the homogeneous catalytic subunit is determined as 30,000. When catalytic and regulatory subunits were mixed, the decrease of phosphotransferase activity was observed.", "contents": "[Separation of catalytic and regulatory subunits of pigeon breast muscle protein kinase]. The separation of catalytic cAMP-independent and regulatory cAMP-binding subunits of pigeon breast muscle protein kinase was performed after the treatment of the holoenzyme by cAMP. The molecular weight of the homogeneous catalytic subunit is determined as 30,000. When catalytic and regulatory subunits were mixed, the decrease of phosphotransferase activity was observed."}
{"id": "PMID:203337", "title": "[Conformation of cytochrome c, adsorbed on different substrates].", "content": "Visible spectra of cytochrome c adsorbed on solid supports and on the same supports covered with monolayers of lecithin and cholesterol were studied. It was shown that absorption spectra of high spin cytochrome c and pK of transition from low to high spin form depend on the nature of adsorbent surface.", "contents": "[Conformation of cytochrome c, adsorbed on different substrates]. Visible spectra of cytochrome c adsorbed on solid supports and on the same supports covered with monolayers of lecithin and cholesterol were studied. It was shown that absorption spectra of high spin cytochrome c and pK of transition from low to high spin form depend on the nature of adsorbent surface."}
{"id": "PMID:203343", "title": "REM sleep and the concept of vigilance.", "content": "Several writers, notably Montague Ullman and Frederick Snyder, conceive of REM sleep and the associated state of vivid dreaming as periods of vigilance. In Ullman's conceptualization, the emphasis is on dreaming in humans, whereas Snyder is concerned with REM sleep (activated sleep) in subhuman organisms. In this paper several objections to the sentinel and vigilance theories are raised, and a modified concept of vigilance, linking it with learning and memory, is put forward.", "contents": "REM sleep and the concept of vigilance. Several writers, notably Montague Ullman and Frederick Snyder, conceive of REM sleep and the associated state of vivid dreaming as periods of vigilance. In Ullman's conceptualization, the emphasis is on dreaming in humans, whereas Snyder is concerned with REM sleep (activated sleep) in subhuman organisms. In this paper several objections to the sentinel and vigilance theories are raised, and a modified concept of vigilance, linking it with learning and memory, is put forward."}
{"id": "PMID:203344", "title": "Twenty-four-hour recording in REM-narcoleptics with special reference to nocturnal sleep disruption.", "content": "Twenty narcoleptic patients and ten age-matched normals were polygraphically monitored for 58 consecutive hours. All subjects were on regimented sleep (hours between 2230 and 0700). Group A (11 patients and 10 normals) had enforced wakefulness during the day whereas Group B (9 patients) were permitted to sleep (mean = 2 1/2 hr.). On day 2, all subjects were permitted to sleep for 15-min periods every 2 hr. In narcoloptics, sleep recordings demonstrated a reduction of sleep latency, an increase of stage 1, and a decrease in stages 3 and 4 compared to normals, but total REM time and percentage of REM sleep were similar. Groups A and B showed no difference in the incidence of nocturnal awakenings. REM cyclic periodicity was larger in narcoleptics who also demonstrated a REM-sleep fragmentation. This fragmentation became more pronounced as time passed, with several shifts from REM to wakefulness and stage 1. Narcoleptics present REM onset sleep period but also show an inability to remain in REM sleep.", "contents": "Twenty-four-hour recording in REM-narcoleptics with special reference to nocturnal sleep disruption. Twenty narcoleptic patients and ten age-matched normals were polygraphically monitored for 58 consecutive hours. All subjects were on regimented sleep (hours between 2230 and 0700). Group A (11 patients and 10 normals) had enforced wakefulness during the day whereas Group B (9 patients) were permitted to sleep (mean = 2 1/2 hr.). On day 2, all subjects were permitted to sleep for 15-min periods every 2 hr. In narcoloptics, sleep recordings demonstrated a reduction of sleep latency, an increase of stage 1, and a decrease in stages 3 and 4 compared to normals, but total REM time and percentage of REM sleep were similar. Groups A and B showed no difference in the incidence of nocturnal awakenings. REM cyclic periodicity was larger in narcoleptics who also demonstrated a REM-sleep fragmentation. This fragmentation became more pronounced as time passed, with several shifts from REM to wakefulness and stage 1. Narcoleptics present REM onset sleep period but also show an inability to remain in REM sleep."}
{"id": "PMID:203345", "title": "Paradoxical sleep and depth perception.", "content": "It has been hypothesised that one possible function of paradoxical (REM) sleep is the maintenance of facilitation of co-ordinated eye movements. A prediction from this hypothesis is that binocular depth perception will be more accurate at the end of periods of paradoxical sleep than at the beginning. The results from previous studies are conflicting. Using two groups of eight healthy male volunteers in a two factor repeated measures design, it was found that for a period of paradoxical sleep in the second half of the night only, there was an improvement in binocular depth perception accuracy between the beginning and end of paradoxical sleep. The accuracy at the end of the paradoxical sleep was not significantly different to that on going to bed or on awakening in the morning; the effect was due to a large decrease in accuracy at the start of the REM period. There was no effect of paradoxical sleep on binocular depth perception in the early part of the night. Monocular depth perception accuracy was unaffected by paradoxical sleep.", "contents": "Paradoxical sleep and depth perception. It has been hypothesised that one possible function of paradoxical (REM) sleep is the maintenance of facilitation of co-ordinated eye movements. A prediction from this hypothesis is that binocular depth perception will be more accurate at the end of periods of paradoxical sleep than at the beginning. The results from previous studies are conflicting. Using two groups of eight healthy male volunteers in a two factor repeated measures design, it was found that for a period of paradoxical sleep in the second half of the night only, there was an improvement in binocular depth perception accuracy between the beginning and end of paradoxical sleep. The accuracy at the end of the paradoxical sleep was not significantly different to that on going to bed or on awakening in the morning; the effect was due to a large decrease in accuracy at the start of the REM period. There was no effect of paradoxical sleep on binocular depth perception in the early part of the night. Monocular depth perception accuracy was unaffected by paradoxical sleep."}
{"id": "PMID:203348", "title": "Serum thymic factor and the neuromuscular transmission.", "content": "The effect of Serum Thymic Factor (FTS) on neuromuscular transmission has been studied in vivo by electromyographic assay. As no modification of muscle tetanus pattern was detected, the involvement of this factor in the pathology of thymus disorders leading to myasthenia is unlikely.", "contents": "Serum thymic factor and the neuromuscular transmission. The effect of Serum Thymic Factor (FTS) on neuromuscular transmission has been studied in vivo by electromyographic assay. As no modification of muscle tetanus pattern was detected, the involvement of this factor in the pathology of thymus disorders leading to myasthenia is unlikely."}
{"id": "PMID:203349", "title": "Possible involvement of natural killer cells in bone marrow graft rejection.", "content": "In the present study comparison between Natural killer (NK) cells and cells responsible for rejection of bone marrow grafts was made. Both cell populations were found to be inhibited by cyclophosphamide, silica, carrageenan, and C. parvum. The reactivity of both cell populations occurred late in life and was not expressed in infant mice. Mice tolerant to bone marrow grafts and, therefore, accepting parental marrow transplants showed also decreased NK cell reactivities. These common features between NK cells and bone marrow effector cells suggest but not prove that these cells could represent the same cell population.", "contents": "Possible involvement of natural killer cells in bone marrow graft rejection. In the present study comparison between Natural killer (NK) cells and cells responsible for rejection of bone marrow grafts was made. Both cell populations were found to be inhibited by cyclophosphamide, silica, carrageenan, and C. parvum. The reactivity of both cell populations occurred late in life and was not expressed in infant mice. Mice tolerant to bone marrow grafts and, therefore, accepting parental marrow transplants showed also decreased NK cell reactivities. These common features between NK cells and bone marrow effector cells suggest but not prove that these cells could represent the same cell population."}
{"id": "PMID:203351", "title": "[ATPase activity of the smooth and rough microsomal subfractions of the heart and liver in rabbits with a short-term microcirculatory disorder].", "content": "Short-time disturbances of the microcirculation in rabbits had a different influence on the ATP-ase activity of smooth and rough microsomes of the liver and heart. Mg+2ATP-ase activity in the liver decreased in both microsome fractions; as in the heart, the enzyme activity increased only in the smooth (light) microsomes.", "contents": "[ATPase activity of the smooth and rough microsomal subfractions of the heart and liver in rabbits with a short-term microcirculatory disorder]. Short-time disturbances of the microcirculation in rabbits had a different influence on the ATP-ase activity of smooth and rough microsomes of the liver and heart. Mg+2ATP-ase activity in the liver decreased in both microsome fractions; as in the heart, the enzyme activity increased only in the smooth (light) microsomes."}
{"id": "PMID:203352", "title": "[Adenosine deaminase activity in hepatomas of varying degrees of malignancy].", "content": "In highly malignant Gelshtein 22A hepatcma and ascites Ehrlich carcinoma adenosine deaminase activity was found to be reduced 3-fold as compared with that of the normal mouse liver. In less malignant hepatomas adenosine deaminase activity drops only by 20%. A certain reduction of adenosine deaminase activity was also noted in the liver to tumour-bearing mice.", "contents": "[Adenosine deaminase activity in hepatomas of varying degrees of malignancy]. In highly malignant Gelshtein 22A hepatcma and ascites Ehrlich carcinoma adenosine deaminase activity was found to be reduced 3-fold as compared with that of the normal mouse liver. In less malignant hepatomas adenosine deaminase activity drops only by 20%. A certain reduction of adenosine deaminase activity was also noted in the liver to tumour-bearing mice."}
{"id": "PMID:203353", "title": "[Cultivation of L strain mouse fibroblasts on silica gel plates].", "content": "A method for cultivation of mice fibroblasts, strain L, using silicagel slides, prepared with \"KSK\" silicagel, was developed Sterile, free of organic compounds, silicagel slides prepared for Petri dishes or test tubes can be successfully used as a solid medium promoting normal development of the culture.", "contents": "[Cultivation of L strain mouse fibroblasts on silica gel plates]. A method for cultivation of mice fibroblasts, strain L, using silicagel slides, prepared with \"KSK\" silicagel, was developed Sterile, free of organic compounds, silicagel slides prepared for Petri dishes or test tubes can be successfully used as a solid medium promoting normal development of the culture."}
{"id": "PMID:203356", "title": "Enhancement by oxotremorine of acetylcholine release from the rat phrenic nerve.", "content": "Oxotremorine (10.5 micron) produced a paralytic effect on twitch responses of rat diaphragm in vitro to direct and indirect stimulation. 2 The paralytic effect of oxotremorine was absent when the diaphragm was stimulated directly in the presence of hemicholinium-3 (0.42 mM), at a time when twitch responses to indirect stimulation ceased completely. 3 Oxotremorine, at two different pharmacologically active doses, strikingly increased the resting as well as electrically evoked release of acetylcholine into the bathing fluid from the phrenic nerve-diaphragm preparation. 4 This presynaptic effect of oxotremorine may explain its pharmacological effects at the cholinergic synapses studied so far.", "contents": "Enhancement by oxotremorine of acetylcholine release from the rat phrenic nerve. Oxotremorine (10.5 micron) produced a paralytic effect on twitch responses of rat diaphragm in vitro to direct and indirect stimulation. 2 The paralytic effect of oxotremorine was absent when the diaphragm was stimulated directly in the presence of hemicholinium-3 (0.42 mM), at a time when twitch responses to indirect stimulation ceased completely. 3 Oxotremorine, at two different pharmacologically active doses, strikingly increased the resting as well as electrically evoked release of acetylcholine into the bathing fluid from the phrenic nerve-diaphragm preparation. 4 This presynaptic effect of oxotremorine may explain its pharmacological effects at the cholinergic synapses studied so far."}
{"id": "PMID:203357", "title": "Responses of the pituitary-adrenal system of the pig to environmental changes and drugs.", "content": "1 The reactivity of the pituitary-adrenal axis of the young pig was tested for its suitability as a sensitive index for any discomfort that might be experienced under certain conditions of intensive husbandry.2 In a thermoneutral environment, most undisturbed piglets showed only slight variations in the plasma concentrations of adrenocorticotrophic hormone (ACTH) and corticosteroids.3 Stimuli such as exposure to ambient temperatures of +40 degrees C or -5 degrees C were required to cause large rises in the plasma concentrations of ACTH and corticosteroids.4 Apparently milder stimuli, such as change of environment, slight frustration or changes in ambient temperatures between +5 degrees C and +30 degrees C only rarely caused a significant rise in plasma corticosteroids. Thus changes in plasma corticosteroid concentrations are not a sensitive index for the reaction of a piglet to its environment.5 Increases in plasma ACTH concentrations occurred faster than those of the corticosteroids, were larger when expressed as a percentage of the basal values and occurred following relatively small disturbances such as omission of the reward in an operant behaviour test when corticosteroid changes were often not detectable. Thus rises in plasma ACTH might be a useful indication that a given situation is disturbing to a pig. The reaction of plasma ACTH concentrations to chronic irritations as they might occur in intensive husbandry remains to be investigated.6 Azaperone (2 mg/kg i.m.), a drug which is used as a sedative in pigs, caused a rise of about 50% in plasma corticosteroid concentrations. It did not diminish the large steroid output seen when the animals were exposed to high and low ambient temperatures.", "contents": "Responses of the pituitary-adrenal system of the pig to environmental changes and drugs. 1 The reactivity of the pituitary-adrenal axis of the young pig was tested for its suitability as a sensitive index for any discomfort that might be experienced under certain conditions of intensive husbandry.2 In a thermoneutral environment, most undisturbed piglets showed only slight variations in the plasma concentrations of adrenocorticotrophic hormone (ACTH) and corticosteroids.3 Stimuli such as exposure to ambient temperatures of +40 degrees C or -5 degrees C were required to cause large rises in the plasma concentrations of ACTH and corticosteroids.4 Apparently milder stimuli, such as change of environment, slight frustration or changes in ambient temperatures between +5 degrees C and +30 degrees C only rarely caused a significant rise in plasma corticosteroids. Thus changes in plasma corticosteroid concentrations are not a sensitive index for the reaction of a piglet to its environment.5 Increases in plasma ACTH concentrations occurred faster than those of the corticosteroids, were larger when expressed as a percentage of the basal values and occurred following relatively small disturbances such as omission of the reward in an operant behaviour test when corticosteroid changes were often not detectable. Thus rises in plasma ACTH might be a useful indication that a given situation is disturbing to a pig. The reaction of plasma ACTH concentrations to chronic irritations as they might occur in intensive husbandry remains to be investigated.6 Azaperone (2 mg/kg i.m.), a drug which is used as a sedative in pigs, caused a rise of about 50% in plasma corticosteroid concentrations. It did not diminish the large steroid output seen when the animals were exposed to high and low ambient temperatures."}
{"id": "PMID:203363", "title": "Identification of functionally related neural assemblies.", "content": "Present-day techniques of multiple-electrode together with computer-aided separation of impulses arising from  different neurons permit the simultaneous recording of nerve-impulse timings in sets of neurons exceeding 20 in number. This in turn makes it feasible to search for functional groups of neurons, defined as subsets that tend to fire in near simultaneity significantly more often than would independent neurons at corresponding mean rates. A statistical technique is described that permits  the detection and identification of such functional groups. The method is accretional, based on identification of associated neurons through interative application of a significance test on multiple coincidences of neuronal firings within an observational window. Examples of the operation of the method and indications as to its sensitivity are furnished through computer simulations of neural networks. The entire algorithm may be used as a screening technique to select smaller groups of neurons for cross-correlational and related finer-grained temporal analyses, or it may be used in its own right to detect and characterize functional groups that are not distinguishable by other statistical procedures.", "contents": "Identification of functionally related neural assemblies. Present-day techniques of multiple-electrode together with computer-aided separation of impulses arising from  different neurons permit the simultaneous recording of nerve-impulse timings in sets of neurons exceeding 20 in number. This in turn makes it feasible to search for functional groups of neurons, defined as subsets that tend to fire in near simultaneity significantly more often than would independent neurons at corresponding mean rates. A statistical technique is described that permits  the detection and identification of such functional groups. The method is accretional, based on identification of associated neurons through interative application of a significance test on multiple coincidences of neuronal firings within an observational window. Examples of the operation of the method and indications as to its sensitivity are furnished through computer simulations of neural networks. The entire algorithm may be used as a screening technique to select smaller groups of neurons for cross-correlational and related finer-grained temporal analyses, or it may be used in its own right to detect and characterize functional groups that are not distinguishable by other statistical procedures."}
{"id": "PMID:203365", "title": "Accumulation of cyclic adenosine 3',5'-monophosphate in human cerebellar cortex slices: effect of monoamine receptor agonists and antagonists.", "content": "Noradrenaline, isoproterenol, adrenaline or clonidine stimulate cyclic AMP formation in human cerebellar cortex 15-20 fold and serotonin or dopamine 3-fold. The increase by noradrenaline or clonidine is dose-dependent. Propranolol completely blocks the increase induced by noradrenaline or isoproterenol but not that by clonidine. Phentolamine was ineffective in blocking cyclic AMP formation induced by noradrenaline, isoproterenol, adrenaline or clonidine. Chlorpromazine completely blocked the increase induced by noradrenaline, isoproterenol, clonidine, serotonin or dopamine.", "contents": "Accumulation of cyclic adenosine 3',5'-monophosphate in human cerebellar cortex slices: effect of monoamine receptor agonists and antagonists. Noradrenaline, isoproterenol, adrenaline or clonidine stimulate cyclic AMP formation in human cerebellar cortex 15-20 fold and serotonin or dopamine 3-fold. The increase by noradrenaline or clonidine is dose-dependent. Propranolol completely blocks the increase induced by noradrenaline or isoproterenol but not that by clonidine. Phentolamine was ineffective in blocking cyclic AMP formation induced by noradrenaline, isoproterenol, adrenaline or clonidine. Chlorpromazine completely blocked the increase induced by noradrenaline, isoproterenol, clonidine, serotonin or dopamine."}
{"id": "PMID:203371", "title": "[Nociceptive afferent blockade by percutaneous peripheral stimulation in the cat].", "content": "Experiments have been performed in order to study the effects of percutaneous peripheral stimulation (PCPS) both on the transmission of messages elicited by recruiting sensory units of the tooth pulp at the thalamic Centrum Medianum Level and on the jaw opening reflex (JOR). Both evoked potentials and JOR were inhibited by stimuli applied to the limbs by means of percutaneous (needle) electrodes. Observed inhibitory effects were not immediate: there was a latency period and progressive induction of these phenomena. The site of the inhibition is still unknown, nevertheless, the demonstration that PCPS was able to inhibit both evoked potentials in Centrum Medianum and JOR support the hypothesis that the analgesic effects may be due to descending inhibition blocking transmission of nociceptive information through the spinal cord.", "contents": "[Nociceptive afferent blockade by percutaneous peripheral stimulation in the cat]. Experiments have been performed in order to study the effects of percutaneous peripheral stimulation (PCPS) both on the transmission of messages elicited by recruiting sensory units of the tooth pulp at the thalamic Centrum Medianum Level and on the jaw opening reflex (JOR). Both evoked potentials and JOR were inhibited by stimuli applied to the limbs by means of percutaneous (needle) electrodes. Observed inhibitory effects were not immediate: there was a latency period and progressive induction of these phenomena. The site of the inhibition is still unknown, nevertheless, the demonstration that PCPS was able to inhibit both evoked potentials in Centrum Medianum and JOR support the hypothesis that the analgesic effects may be due to descending inhibition blocking transmission of nociceptive information through the spinal cord."}
{"id": "PMID:203372", "title": "[The effect of nalorphine on analgesia induced by peripheral stimulation].", "content": "The blockade of effects induced by percutaneous peripheral stimulation were abolished by injection of an opiate antagonist as nalorphine. Our results lead to the hypothesis that central and peripheral stimulations act by the same mechanism in producing blockade of noxious impulses. One may suggest that peripheral stimulations induce release of endogenous morphine-like substances which in turn give descending inhibition.", "contents": "[The effect of nalorphine on analgesia induced by peripheral stimulation]. The blockade of effects induced by percutaneous peripheral stimulation were abolished by injection of an opiate antagonist as nalorphine. Our results lead to the hypothesis that central and peripheral stimulations act by the same mechanism in producing blockade of noxious impulses. One may suggest that peripheral stimulations induce release of endogenous morphine-like substances which in turn give descending inhibition."}
{"id": "PMID:203373", "title": "[Effect of differentiation of GABA levels in various cell cultures].", "content": "The effect of factors inducing somatic differentiation on cellular GABA level has been investigated. C6 glial cells from a rat astrocytoma present a significantly higher GABA level than the other glial or neuronal cells studied. A significant decrease in GABA levels in most cases parallels the somatic differentiation induced either by withdrawal of fetal serum, or by addition of dibutyryl cyclic AMP to the culture medium.", "contents": "[Effect of differentiation of GABA levels in various cell cultures]. The effect of factors inducing somatic differentiation on cellular GABA level has been investigated. C6 glial cells from a rat astrocytoma present a significantly higher GABA level than the other glial or neuronal cells studied. A significant decrease in GABA levels in most cases parallels the somatic differentiation induced either by withdrawal of fetal serum, or by addition of dibutyryl cyclic AMP to the culture medium."}
{"id": "PMID:203374", "title": "[Enhancement of compensatory renal hypertrophy by beta-1-24 corticotropin in the rat].", "content": "In the rat, the administration of beta1-24-corticotrophin during 7 days following an uninephrectomy enhances significantly the compensatory hypertrophy of the remaining kidney. There is no increase in renal compensatory hypertrophy when ACTH is injected to previously adrenalectomized rats. This action of ACTH could be related to the diabetes mellitus induced by this hormone or to an increase in sodium reabsorption by the tubular epithelial cells.", "contents": "[Enhancement of compensatory renal hypertrophy by beta-1-24 corticotropin in the rat]. In the rat, the administration of beta1-24-corticotrophin during 7 days following an uninephrectomy enhances significantly the compensatory hypertrophy of the remaining kidney. There is no increase in renal compensatory hypertrophy when ACTH is injected to previously adrenalectomized rats. This action of ACTH could be related to the diabetes mellitus induced by this hormone or to an increase in sodium reabsorption by the tubular epithelial cells."}
{"id": "PMID:203375", "title": "Bordetella pertussis in the National Capital Region: prevalent serotype and immunization status of patients.", "content": "Over a 2-year period 67 strains of Bordetella pertussis were identified in 231 single specimens of nasopharyngeal secretions submitted from patients suspected to have whooping cough in the National Capital Region; 89.5% of the identifications were made by culture. Serotype 1,3 was predominant. At least 75% of the patients with bacteriologically confirmed whooping cough had not been fully immunized. There was no evidence that adenoviruses or other viruses played any important etiologic role in the 204 cases of whooping cough or whooping cough syndrome studied virologically.", "contents": "Bordetella pertussis in the National Capital Region: prevalent serotype and immunization status of patients. Over a 2-year period 67 strains of Bordetella pertussis were identified in 231 single specimens of nasopharyngeal secretions submitted from patients suspected to have whooping cough in the National Capital Region; 89.5% of the identifications were made by culture. Serotype 1,3 was predominant. At least 75% of the patients with bacteriologically confirmed whooping cough had not been fully immunized. There was no evidence that adenoviruses or other viruses played any important etiologic role in the 204 cases of whooping cough or whooping cough syndrome studied virologically."}
{"id": "PMID:203377", "title": "Bronchiolar carcinoma: report of 11 cases and review of the literature.", "content": "Eleven cases of bronchiolar carcinoma seen between 1970 and 1975 are reviewed. Roentgenographic manifestations at the time of initial examination included single peripheral nodules, multiple nodules, irregular cavities and a persistent infiltrative form. Microscopic tissue examinations showed two patterns of tumor growth: a papillary form resembling tall columnar cells extending along but not invading the alveolar septal walls and a cribriform pattern represented by inflammatory thickening of the alveolar septal walls and pleomorphic cellular proliferation within luminal spaces. The papillary form was associated with the cavitary lesions. Long term survival is dependent on early recognition of the single peripheral nodule, cavity or small persistent infiltrative form managed by a thoracotomy and lobectomy.", "contents": "Bronchiolar carcinoma: report of 11 cases and review of the literature. Eleven cases of bronchiolar carcinoma seen between 1970 and 1975 are reviewed. Roentgenographic manifestations at the time of initial examination included single peripheral nodules, multiple nodules, irregular cavities and a persistent infiltrative form. Microscopic tissue examinations showed two patterns of tumor growth: a papillary form resembling tall columnar cells extending along but not invading the alveolar septal walls and a cribriform pattern represented by inflammatory thickening of the alveolar septal walls and pleomorphic cellular proliferation within luminal spaces. The papillary form was associated with the cavitary lesions. Long term survival is dependent on early recognition of the single peripheral nodule, cavity or small persistent infiltrative form managed by a thoracotomy and lobectomy."}
{"id": "PMID:203378", "title": "Acute leukemia complicating treatment of glioblastoma multiforme.", "content": "A five-year-old girl developed acute myelomonocytic leukemia after fifteen months of intensive chemotherapy and irradiation for glioblastoma multiforme. The leukemia became manifest while the patient was in a remarkable remission brought about by treatment with high-dose methotrexate with citrovorum rescue. This is the first reported association of these disorders in the same patient. It is possible that the leukemia was induced by the treatment, since both radiation and the chemotherapeutic drugs used have been shown to be leukemogenic in some circumstances. The patient developed leukemia in a setting of relatively normal peripheral blood counts, having had very little myelosuppression from her treatment.", "contents": "Acute leukemia complicating treatment of glioblastoma multiforme. A five-year-old girl developed acute myelomonocytic leukemia after fifteen months of intensive chemotherapy and irradiation for glioblastoma multiforme. The leukemia became manifest while the patient was in a remarkable remission brought about by treatment with high-dose methotrexate with citrovorum rescue. This is the first reported association of these disorders in the same patient. It is possible that the leukemia was induced by the treatment, since both radiation and the chemotherapeutic drugs used have been shown to be leukemogenic in some circumstances. The patient developed leukemia in a setting of relatively normal peripheral blood counts, having had very little myelosuppression from her treatment."}
{"id": "PMID:203379", "title": "Oat cell carcinoma (apudoma) of the esophagus: a case report.", "content": "An oat cell carcinoma occurring in the esophagus of a 62-year-old man is described. A strong argyrophilia of the oat cells together with the presence electron microscopically of neurosecretory type granules in their cytoplasm suggests a derivation of this tumor from the cells of the APUD series, and the tumor is diagnosed as apudoma. An aberrant columnar epithelium on the esophageal surface is presumed to be the source of its origin. A rapid postoperative course of the patient despite a rather circumscribed growth pattern of the primary tumor appears to characterize the clinical aspect of this case. An apparent accumulation of the cases with esophageal apudoma in Japan is discussed.", "contents": "Oat cell carcinoma (apudoma) of the esophagus: a case report. An oat cell carcinoma occurring in the esophagus of a 62-year-old man is described. A strong argyrophilia of the oat cells together with the presence electron microscopically of neurosecretory type granules in their cytoplasm suggests a derivation of this tumor from the cells of the APUD series, and the tumor is diagnosed as apudoma. An aberrant columnar epithelium on the esophageal surface is presumed to be the source of its origin. A rapid postoperative course of the patient despite a rather circumscribed growth pattern of the primary tumor appears to characterize the clinical aspect of this case. An apparent accumulation of the cases with esophageal apudoma in Japan is discussed."}
{"id": "PMID:203380", "title": "Cyclic nucleotide concentrations in 1,2-dimethylhydrazine induced rat colon adenocarcinoma.", "content": "The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) in colonic tumors induced in adult male Holtzman rats by 1,2-dimethylhydrazine (DMH) were found to be 1/2 the concentration found in normal large bowel tissue. Intracellular concentrations of guanosine 3'-5'-cyclic monophosphate (cGMP) in the neoplastic cells were twice the normal colon level. The concentrations of these two cyclic nucleotides were relatively constant throughout the normal colon. Thus, the anomalous tumor cyclic nucleotide concentrations are attributed to the specific cell population of the lesion and not to the site of development within the colon.", "contents": "Cyclic nucleotide concentrations in 1,2-dimethylhydrazine induced rat colon adenocarcinoma. The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) in colonic tumors induced in adult male Holtzman rats by 1,2-dimethylhydrazine (DMH) were found to be 1/2 the concentration found in normal large bowel tissue. Intracellular concentrations of guanosine 3'-5'-cyclic monophosphate (cGMP) in the neoplastic cells were twice the normal colon level. The concentrations of these two cyclic nucleotides were relatively constant throughout the normal colon. Thus, the anomalous tumor cyclic nucleotide concentrations are attributed to the specific cell population of the lesion and not to the site of development within the colon."}
{"id": "PMID:203381", "title": "Globin messenger RNA content in hepatomas: a test of retrogenesis.", "content": "The globin mRNA content of foetal, neonatal and normal adult liver and of the transplantable Morris hepatoma 5123C and host liver of animals carrying the tumour was measured using molecular hybridization of total nucleic acid extracts from these tissues with a complementary DNA copy of globin mRNA from rabbit reticulocytes. The purpose of these experiments was to determine, as a test at the molecular level of the retrogenesis hypothesis, if the gene for foetal globin is activated in neoplastic hepatic tissue or induced in host liver. These experiments did not detect any foetal globin mRNA in the hepatoma or host liver nucleic acid extracts in spite of the increase in haemopoietic activity induced in host animals as a consequence of tumour bearing.", "contents": "Globin messenger RNA content in hepatomas: a test of retrogenesis. The globin mRNA content of foetal, neonatal and normal adult liver and of the transplantable Morris hepatoma 5123C and host liver of animals carrying the tumour was measured using molecular hybridization of total nucleic acid extracts from these tissues with a complementary DNA copy of globin mRNA from rabbit reticulocytes. The purpose of these experiments was to determine, as a test at the molecular level of the retrogenesis hypothesis, if the gene for foetal globin is activated in neoplastic hepatic tissue or induced in host liver. These experiments did not detect any foetal globin mRNA in the hepatoma or host liver nucleic acid extracts in spite of the increase in haemopoietic activity induced in host animals as a consequence of tumour bearing."}
{"id": "PMID:203384", "title": "Equivalent expression of endogenous murine leukemia virus-related genes in C3H/10T1/2 cells and chemically transformed derivative cells.", "content": "The possibility that chemical carcinogens may induce enhanced expression of endogenous C-type RNA tumor virus genes in the absence of intact virus particle production has been partially tested in a model system. Thie was accomplished by measuring the abundance and diversity of murine leukemia virus-related RNA sequences associated with the polyribosome fraction of nontransformed C3H/10T1/2 clone 8 cells and a 3-methylcholanthrene-transformed derivative clone. Although both clones are virus nonproducers, they were found to contain significant amounts of polyadenylate-containing murine leukemia virus-related RNA sequences; however, both the types and quantities of such sequences appear indistinguishable in both clones. These results suggest that expression of the corresponding gene sequences into RNA is not related to the maintenance of the transformed state in these chemically transformed cells.", "contents": "Equivalent expression of endogenous murine leukemia virus-related genes in C3H/10T1/2 cells and chemically transformed derivative cells. The possibility that chemical carcinogens may induce enhanced expression of endogenous C-type RNA tumor virus genes in the absence of intact virus particle production has been partially tested in a model system. Thie was accomplished by measuring the abundance and diversity of murine leukemia virus-related RNA sequences associated with the polyribosome fraction of nontransformed C3H/10T1/2 clone 8 cells and a 3-methylcholanthrene-transformed derivative clone. Although both clones are virus nonproducers, they were found to contain significant amounts of polyadenylate-containing murine leukemia virus-related RNA sequences; however, both the types and quantities of such sequences appear indistinguishable in both clones. These results suggest that expression of the corresponding gene sequences into RNA is not related to the maintenance of the transformed state in these chemically transformed cells."}
{"id": "PMID:203387", "title": "A comparison of methods for the isolation of carcinoembryonic antigen.", "content": "Carcinoembryonic antigen (CEA) was isolated from a human tumor with 0.02 M sodium phosphate containing 0.14 M NaCl (pH 7.0) (saline) and further studied after treatment with perchloric acid or 8 M urea. Preparations CEA obtained from saline homogenates and both methods of treatment were characterized by isoelectric focusing and gel filtration. Perchloric acid treatment resulted in an approximate 10-fold decrease in protein and a significant loss of CEA as compared to the saline- and urea-treated material. Isoelectric focusing revealed that the resultant CEA subpopulations were dependent upon the method of isolation. Urea- and saline-treated material showed complex isoelectric patterns that were quantitatively dissimilar. Perchloric acid-treated material showed a comparatively simple isoelectric pattern that was not significantly affected by electrofocusing in the presence of urea. Gel filtration on ACA 34 of the CEA obtained from each method of isolation resulted in two peaks of activity. The first peak corresponded to the void volume of the column, and the second peak coeluted with commercially available purified 125I-labeled CEA. Centrifugation of the peaks obtained resulted in a significantly greater loss of CEA from the void peak of each isolation procedure. The amount of CEA lost from the void peaks following centrifugation differed with each method of isolation and suggested the presence of aggregates.", "contents": "A comparison of methods for the isolation of carcinoembryonic antigen. Carcinoembryonic antigen (CEA) was isolated from a human tumor with 0.02 M sodium phosphate containing 0.14 M NaCl (pH 7.0) (saline) and further studied after treatment with perchloric acid or 8 M urea. Preparations CEA obtained from saline homogenates and both methods of treatment were characterized by isoelectric focusing and gel filtration. Perchloric acid treatment resulted in an approximate 10-fold decrease in protein and a significant loss of CEA as compared to the saline- and urea-treated material. Isoelectric focusing revealed that the resultant CEA subpopulations were dependent upon the method of isolation. Urea- and saline-treated material showed complex isoelectric patterns that were quantitatively dissimilar. Perchloric acid-treated material showed a comparatively simple isoelectric pattern that was not significantly affected by electrofocusing in the presence of urea. Gel filtration on ACA 34 of the CEA obtained from each method of isolation resulted in two peaks of activity. The first peak corresponded to the void volume of the column, and the second peak coeluted with commercially available purified 125I-labeled CEA. Centrifugation of the peaks obtained resulted in a significantly greater loss of CEA from the void peak of each isolation procedure. The amount of CEA lost from the void peaks following centrifugation differed with each method of isolation and suggested the presence of aggregates."}
{"id": "PMID:203388", "title": "Differential inhibition of the rejoining of X-ray-induced DNA strand breaks in normal and transformed human fibroblasts treated with 1,3-bis(2-chloroethyl)-1-nitrosourea in vitro.", "content": "The effects of 1,3-bis(2-chloroethyl)-1-nitrosourea on the rejoining of X-ray-induced DNA strand breaks were examined in normal human fibroblasts (WI-38) and a simian virus 40-transformed derivative (VA-13) with the use of alkaline sucrose sedimentation. 1,3-Bis(2-chloroethyl)-1-nitrosourea was capable of partially inhibiting repair of X-ray-produced DNA strand breaks in both cell types when the drug was added to the culture medium immediately after X-irradiation. However, when 1,3-bis(2-chloroethyl)-1-nitrosourea exposure preceded X-ray by 1 hr, DNA repair was inhibited to a much greater extent than it was when 1,3-bis(2-chloroethyl)-1-nitrosourea followed X-ray. The inhibition of DNA repair by 1,3-bis(2-chloroethyl)-1-nitrosourea appeared to be complete in the transformed VA-13 cells, while only partial inhibition of repair was observed in the normal WI-38 cells.", "contents": "Differential inhibition of the rejoining of X-ray-induced DNA strand breaks in normal and transformed human fibroblasts treated with 1,3-bis(2-chloroethyl)-1-nitrosourea in vitro. The effects of 1,3-bis(2-chloroethyl)-1-nitrosourea on the rejoining of X-ray-induced DNA strand breaks were examined in normal human fibroblasts (WI-38) and a simian virus 40-transformed derivative (VA-13) with the use of alkaline sucrose sedimentation. 1,3-Bis(2-chloroethyl)-1-nitrosourea was capable of partially inhibiting repair of X-ray-produced DNA strand breaks in both cell types when the drug was added to the culture medium immediately after X-irradiation. However, when 1,3-bis(2-chloroethyl)-1-nitrosourea exposure preceded X-ray by 1 hr, DNA repair was inhibited to a much greater extent than it was when 1,3-bis(2-chloroethyl)-1-nitrosourea followed X-ray. The inhibition of DNA repair by 1,3-bis(2-chloroethyl)-1-nitrosourea appeared to be complete in the transformed VA-13 cells, while only partial inhibition of repair was observed in the normal WI-38 cells."}
{"id": "PMID:203389", "title": "Activation of C-type virus during chemically induced leukemogenesis in mice.", "content": "Repeated percutaneous applications of 7,12-dimethylbenz(a)anthracene on weaning DBA/2 and ST/a mice induced 100% leukemias with short latency periods. Endogenous C-type viruses were activated during the treatment as evidenced by (a) increased expression of the murine leukemia virus major core protein, p30, in blood and spleens and (b) increased frequency of detection of ecotropic virus by cocultivation of the splenocytes with SC-1 cells. The treatment did not affect p30 expression in several nonlymphoid organs, and detection of xenotropic viruses in the splenocytes was decreased. Virus expression did not correlate with the progression of disease in that (a) high p30 levels were generally found in mice with relatively low spleen weights and (b) p30 levels had no obvious connection to survival of the individual. 7,12-Dimethylbenz(a)anthracene treatment had little influence on p30 expression in spleens and blood from C3H and BALB/c mice, which are less sensitive to 7,12-dimethylbenz(a)anthracene-induced leukemogenesis. The results indicate an association of C-type virus activation with chemical induction of leukemia but do not necessarily imply an etiological role of the virus in the disease.", "contents": "Activation of C-type virus during chemically induced leukemogenesis in mice. Repeated percutaneous applications of 7,12-dimethylbenz(a)anthracene on weaning DBA/2 and ST/a mice induced 100% leukemias with short latency periods. Endogenous C-type viruses were activated during the treatment as evidenced by (a) increased expression of the murine leukemia virus major core protein, p30, in blood and spleens and (b) increased frequency of detection of ecotropic virus by cocultivation of the splenocytes with SC-1 cells. The treatment did not affect p30 expression in several nonlymphoid organs, and detection of xenotropic viruses in the splenocytes was decreased. Virus expression did not correlate with the progression of disease in that (a) high p30 levels were generally found in mice with relatively low spleen weights and (b) p30 levels had no obvious connection to survival of the individual. 7,12-Dimethylbenz(a)anthracene treatment had little influence on p30 expression in spleens and blood from C3H and BALB/c mice, which are less sensitive to 7,12-dimethylbenz(a)anthracene-induced leukemogenesis. The results indicate an association of C-type virus activation with chemical induction of leukemia but do not necessarily imply an etiological role of the virus in the disease."}
{"id": "PMID:203390", "title": "Cyclic adenosine 3':5'-monophosphate and methotrexate transport in L1210 cells.", "content": "Treatment of L1210 cells with glucose, 1-methyl-3-isobutylxanthine, theophylline, and prostaglandins E1 and E2 was used to increase to varying degrees the endogenous level of cyclic adenosine 3':5'-monophosphate (cAMP). In an inverse manner these agents decreased the rate of methotrexate (MTX) transport into the cells. Azide, conversely, lowered the cAMP level and enhanced MTX transport. Quantitative information about this relationship was obtained by plotting the reciprocal rates of MTX transport as a function of cAMP levels. These data suggest that MTX transport is regulated by the level of cAMP.", "contents": "Cyclic adenosine 3':5'-monophosphate and methotrexate transport in L1210 cells. Treatment of L1210 cells with glucose, 1-methyl-3-isobutylxanthine, theophylline, and prostaglandins E1 and E2 was used to increase to varying degrees the endogenous level of cyclic adenosine 3':5'-monophosphate (cAMP). In an inverse manner these agents decreased the rate of methotrexate (MTX) transport into the cells. Azide, conversely, lowered the cAMP level and enhanced MTX transport. Quantitative information about this relationship was obtained by plotting the reciprocal rates of MTX transport as a function of cAMP levels. These data suggest that MTX transport is regulated by the level of cAMP."}
{"id": "PMID:203397", "title": "Oxidative phosphorylation and aspects of calcium metabolism in myocardia of hypercholesterolaemic swine with moderate coronary atherosclerosis.", "content": "Aspects of myocardial oxidative phosphorylation and Ca2+ metabolism were studied in a swine model in which coronary atherosclerosis was induced by a combination of denudation of the endothelium of the coronary arteries plus 7--11 months of feeding a high fat--high cholesterol diet. By microscopy, a moderate amount of coronary atherosclerosis was present at the time of sacrifice, and 2 of the 14 swine hearts had old myocardial infarcts. Myocardial mitochondria from grossly normal areas showed partial uncoupling and decreased state 3 O2 uptake with 3 of 4 substrates tested. In addition, Ca2+ stimulated mitochondrial respiration was decreased in the atherosclerotic swine. In the sarcoplasmic reticulum Ca2+ uptake under conditions of heavy loading was greater in the atherosclerotic swine than in control animals. The degree of atherosclerosis was not great enough to suggest that persistent myocardial ischaemia was present. Possibly coronary artery spasm induced an intermittent ischaemia resulting in the metabolic abnormalities observed, or the changes may have been brought about by the effects of the high fat--high cholesterol diet on subcellular membranes.", "contents": "Oxidative phosphorylation and aspects of calcium metabolism in myocardia of hypercholesterolaemic swine with moderate coronary atherosclerosis. Aspects of myocardial oxidative phosphorylation and Ca2+ metabolism were studied in a swine model in which coronary atherosclerosis was induced by a combination of denudation of the endothelium of the coronary arteries plus 7--11 months of feeding a high fat--high cholesterol diet. By microscopy, a moderate amount of coronary atherosclerosis was present at the time of sacrifice, and 2 of the 14 swine hearts had old myocardial infarcts. Myocardial mitochondria from grossly normal areas showed partial uncoupling and decreased state 3 O2 uptake with 3 of 4 substrates tested. In addition, Ca2+ stimulated mitochondrial respiration was decreased in the atherosclerotic swine. In the sarcoplasmic reticulum Ca2+ uptake under conditions of heavy loading was greater in the atherosclerotic swine than in control animals. The degree of atherosclerosis was not great enough to suggest that persistent myocardial ischaemia was present. Possibly coronary artery spasm induced an intermittent ischaemia resulting in the metabolic abnormalities observed, or the changes may have been brought about by the effects of the high fat--high cholesterol diet on subcellular membranes."}
{"id": "PMID:203400", "title": "The eyes of mesopelagic crustaceans. II. Streetsia challengeri (amphipoda).", "content": "In Streetsia challengeri left and right eyes have fused and become a single cylindrical photoreceptor, which occupies the basal half of a forward directed head projection. This unusual compound eye consists of approximately 2500 ommatidia, which are arranged in such a way that the animal has almost circumferential vision, but cannot look ahead or behind. It is thought that the eye operates on light-guide principles, and that the crystalline cones are the major dioptric component. Ommatidia in anterior-posterior rows show a greater overlap of visual fields than dorso-ventrally arranged ommatidia. Cone layer and retinula are separated by a 4 micrometer thick screen-membrane, which contains tiny pigment granules of 0.15 micrometer diameter. Cells of unknown function and origin, containing unusual multitubular organelles, are regularly found near the proximal ends of the crystalline cone threads. The twisted rhabdoms measure 18--20 micrometer in diameter, and consist of microvilli 0.05 micrometer in width, which belong to five retinula cells and which show no trace of disintegration. The position of interommatidial screening pigment, the density of retinula cell vesicles and inclusions, and the narrowness of the perirhabdomal space all suggest that the eyes have been light-adapted at the time of fixation for electron microscopy. The retinula cell nuclei lie on the proximal side of the heavily pigmented basement membrane. A tapetum or basal retinula cells are not developed. It is concluded that the eye optimally combines acuity with sensitivity, and that for distance estimation parallax may be important.", "contents": "The eyes of mesopelagic crustaceans. II. Streetsia challengeri (amphipoda). In Streetsia challengeri left and right eyes have fused and become a single cylindrical photoreceptor, which occupies the basal half of a forward directed head projection. This unusual compound eye consists of approximately 2500 ommatidia, which are arranged in such a way that the animal has almost circumferential vision, but cannot look ahead or behind. It is thought that the eye operates on light-guide principles, and that the crystalline cones are the major dioptric component. Ommatidia in anterior-posterior rows show a greater overlap of visual fields than dorso-ventrally arranged ommatidia. Cone layer and retinula are separated by a 4 micrometer thick screen-membrane, which contains tiny pigment granules of 0.15 micrometer diameter. Cells of unknown function and origin, containing unusual multitubular organelles, are regularly found near the proximal ends of the crystalline cone threads. The twisted rhabdoms measure 18--20 micrometer in diameter, and consist of microvilli 0.05 micrometer in width, which belong to five retinula cells and which show no trace of disintegration. The position of interommatidial screening pigment, the density of retinula cell vesicles and inclusions, and the narrowness of the perirhabdomal space all suggest that the eyes have been light-adapted at the time of fixation for electron microscopy. The retinula cell nuclei lie on the proximal side of the heavily pigmented basement membrane. A tapetum or basal retinula cells are not developed. It is concluded that the eye optimally combines acuity with sensitivity, and that for distance estimation parallax may be important."}
{"id": "PMID:203401", "title": "Fine structure of the eyes of orb-weavers, Argiope amoena L. Koch (Aranea: Argiopidae). 2. The anterolateral, posterolateral and posterommedial eyes.", "content": "The anterolateral eye, the posterolateral eye and the posteromedial eye of the web-building spider, Argiope amoena have been examined by light and electron microscopy. The dioptric apparatus of all three eyes is similar in structure, and consists of a cornea, a lens and a vitreous body. The retina contains monopolar receptor cells, the cell bodies of which are present beneath the vitreous body in all three eyes. Proximal processes of the receptor cells form rhabdoms beneath the cell body layer and then extend toward the first optic glomerulus as an ocellar nerve. Two distinct patterns of retinal organization are present in the three eyes. In one type the rhabdomic layer of the retina is backed by a pigmented layer. In the other type the rhabdomic layer is backed by a tapetal reflecting layer. Rhabdomic structure and cytoplasmic inclusions of the receptor cells differ greatly between the two types. The anterolateral eye possesses a single type of retina with the rhabdoms backed by the tapetum. Both the posterolateral and the posteromedial eye are similar in structure, each possessing beneath the common dioptric apparatus retinae of both types.", "contents": "Fine structure of the eyes of orb-weavers, Argiope amoena L. Koch (Aranea: Argiopidae). 2. The anterolateral, posterolateral and posterommedial eyes. The anterolateral eye, the posterolateral eye and the posteromedial eye of the web-building spider, Argiope amoena have been examined by light and electron microscopy. The dioptric apparatus of all three eyes is similar in structure, and consists of a cornea, a lens and a vitreous body. The retina contains monopolar receptor cells, the cell bodies of which are present beneath the vitreous body in all three eyes. Proximal processes of the receptor cells form rhabdoms beneath the cell body layer and then extend toward the first optic glomerulus as an ocellar nerve. Two distinct patterns of retinal organization are present in the three eyes. In one type the rhabdomic layer of the retina is backed by a pigmented layer. In the other type the rhabdomic layer is backed by a tapetal reflecting layer. Rhabdomic structure and cytoplasmic inclusions of the receptor cells differ greatly between the two types. The anterolateral eye possesses a single type of retina with the rhabdoms backed by the tapetum. Both the posterolateral and the posteromedial eye are similar in structure, each possessing beneath the common dioptric apparatus retinae of both types."}
{"id": "PMID:203402", "title": "The compaction of DNA helices into either continuous supercoils or folded-fiber rods and toroids.", "content": "We have investigated by electron microscopy the mechanism of DNA compaction and have found that the double helix has the intrinsic potential to direct its own packaging into two distinctly different and mutally exclusive modes. The mode of DNA packaging is determined by the electrostatic charge density and water activity of the immediate microenvironment of the helix. The two basic structures formed by both linear and covalently closed-circular DNA are: a left-handed supercoil characteristic of minimally charge-shielded DNA, and a smooth rod characteristic of fully charge-shielded DNA. We propose that in the supercoil, the double helix is overwound (increased turn-angle), while in the rod, the helix is folded back and forth on itself. Variation of these two basic structures are the beaded fiber of DNA obtained with partially charge-shielded DNA and the toroid formed by the bending of the DNA rod and fusion of its ends in the presence of certain cations. We compare the DNA packaging inside these in vitro generated structures to DNA packaging in chromatin and viral capsids, and conclude that the packaging of DNA brought about by the use of salts and alcohol closely mimics the packaging behavior of the DNA in vivo, where it is usually complexed with histones or polyamines.", "contents": "The compaction of DNA helices into either continuous supercoils or folded-fiber rods and toroids. We have investigated by electron microscopy the mechanism of DNA compaction and have found that the double helix has the intrinsic potential to direct its own packaging into two distinctly different and mutally exclusive modes. The mode of DNA packaging is determined by the electrostatic charge density and water activity of the immediate microenvironment of the helix. The two basic structures formed by both linear and covalently closed-circular DNA are: a left-handed supercoil characteristic of minimally charge-shielded DNA, and a smooth rod characteristic of fully charge-shielded DNA. We propose that in the supercoil, the double helix is overwound (increased turn-angle), while in the rod, the helix is folded back and forth on itself. Variation of these two basic structures are the beaded fiber of DNA obtained with partially charge-shielded DNA and the toroid formed by the bending of the DNA rod and fusion of its ends in the presence of certain cations. We compare the DNA packaging inside these in vitro generated structures to DNA packaging in chromatin and viral capsids, and conclude that the packaging of DNA brought about by the use of salts and alcohol closely mimics the packaging behavior of the DNA in vivo, where it is usually complexed with histones or polyamines."}
{"id": "PMID:203403", "title": "Nucleotide sequence of the DNA replication origin for human papovavirus BKV: sequence and structural homology with SV40.", "content": "DNA and RNA sequencing techniques were used to obtain the sequence surrounding the origin of DNA replication for human papovavirus BKV. The structure is characterized by a true palindrome of 17 residues followed by two sets of symmetrical sequences and a stretch of 20 AT residues. Within the two symmetrical sequences is a segment containing a strong purine bias, 23 of 26 nucleotides. These structures are similar, if not identical, to those found in the region of the SV40 replication, origin. Within the homologous DNA segments, 60-80% of the BKV and SV40 nucleotides are the same. The remarkable similarity of BKV and SV40 sequences containing the origins of DNA replication would appear to confirm our previous suggestion of an evolutionary relationship between the two genomes. In addition, topological similarities between these sequences suggest the possibility of certain structural requirements for bidirectional replication origins in these superhelical DNAs.", "contents": "Nucleotide sequence of the DNA replication origin for human papovavirus BKV: sequence and structural homology with SV40. DNA and RNA sequencing techniques were used to obtain the sequence surrounding the origin of DNA replication for human papovavirus BKV. The structure is characterized by a true palindrome of 17 residues followed by two sets of symmetrical sequences and a stretch of 20 AT residues. Within the two symmetrical sequences is a segment containing a strong purine bias, 23 of 26 nucleotides. These structures are similar, if not identical, to those found in the region of the SV40 replication, origin. Within the homologous DNA segments, 60-80% of the BKV and SV40 nucleotides are the same. The remarkable similarity of BKV and SV40 sequences containing the origins of DNA replication would appear to confirm our previous suggestion of an evolutionary relationship between the two genomes. In addition, topological similarities between these sequences suggest the possibility of certain structural requirements for bidirectional replication origins in these superhelical DNAs."}
{"id": "PMID:203405", "title": "Characteristics of cellular RNA related to the transforming gene of avian sarcoma viruses.", "content": "Nucleotide sequences (sarc) related to the transforming gene of avian sarcoma viruses are present in the DNA and transcribed into RNA in uninfected avian cells (Stehelin et al., 1976b; Spector et al., 1978). Cytoplasmic RNA containing the sarc sequences has a sedimentation coefficient of 30S, is linked to polyadenylic acid and is present in polyribosomes in a form which can be released by treatment with EDTA. Hence the sarc sequences (complexity = 5 x 10(5) daltons) are part of a larger transcriptional unit (approximately 1.8 x 10(6) daltons), and the sarc RNA appears to serve an as yet unknown messenger function. In addition, the sarc sequences in chicken cells are not linked to RNA transcribed from the provisrus of the endogenous virus RAV-O, since RAV-O cytoplasmic RNA has sedimentation coefficients of 32S and 21S. Comparison of sarc-containing RNA in quail embryo fibroblasts and in quail cells derived from a methylcholanthrene-induced fibrosarcoma revealed no differences with respect to size, polyadenylation or concentration of the RNA in nuclei, cytoplasm and polyribosomes; thus the phenotypic differences between these cells are unlikely to be a consequence of alteration in expression of the sarc sequences.", "contents": "Characteristics of cellular RNA related to the transforming gene of avian sarcoma viruses. Nucleotide sequences (sarc) related to the transforming gene of avian sarcoma viruses are present in the DNA and transcribed into RNA in uninfected avian cells (Stehelin et al., 1976b; Spector et al., 1978). Cytoplasmic RNA containing the sarc sequences has a sedimentation coefficient of 30S, is linked to polyadenylic acid and is present in polyribosomes in a form which can be released by treatment with EDTA. Hence the sarc sequences (complexity = 5 x 10(5) daltons) are part of a larger transcriptional unit (approximately 1.8 x 10(6) daltons), and the sarc RNA appears to serve an as yet unknown messenger function. In addition, the sarc sequences in chicken cells are not linked to RNA transcribed from the provisrus of the endogenous virus RAV-O, since RAV-O cytoplasmic RNA has sedimentation coefficients of 32S and 21S. Comparison of sarc-containing RNA in quail embryo fibroblasts and in quail cells derived from a methylcholanthrene-induced fibrosarcoma revealed no differences with respect to size, polyadenylation or concentration of the RNA in nuclei, cytoplasm and polyribosomes; thus the phenotypic differences between these cells are unlikely to be a consequence of alteration in expression of the sarc sequences."}
{"id": "PMID:203406", "title": "Sites of integration of infectious DNA of avian reticuloendotheliosis viruses in different avian cellular DNAs.", "content": "The pattern of integration for the infectious DNA of two avian reticuloendotheliosis viruses whose DNA is not inactivated by digestion with the restriction endonuclease, Eco RI was determined. High molecular weight DNA from infected chicken, turkey and pheasant cells was digested with Eco RI, electrophoresed through agarose gels and assayed for infectivity. The same patterns of integration of infectious viral DNA were found for these species of avian cells infected at high or low multiplicities with two reticuloendotheliosis viruses. There were multiple sites of integration in acutely infected cells with concomitant cell death. There was a single site of integration in chronically infected cells with no cell death. There were more integrated infectious viral DNA molecules per cell in acutely infected cells than in chronically infected cells. These results are consistent with the hypotheses that the cell death in the acute phase of infection is a result of the integration of the infectious viral DNA at multiple sites, and that only those cells survive that have the infectious viral DNA integrated exclusively at the single site.", "contents": "Sites of integration of infectious DNA of avian reticuloendotheliosis viruses in different avian cellular DNAs. The pattern of integration for the infectious DNA of two avian reticuloendotheliosis viruses whose DNA is not inactivated by digestion with the restriction endonuclease, Eco RI was determined. High molecular weight DNA from infected chicken, turkey and pheasant cells was digested with Eco RI, electrophoresed through agarose gels and assayed for infectivity. The same patterns of integration of infectious viral DNA were found for these species of avian cells infected at high or low multiplicities with two reticuloendotheliosis viruses. There were multiple sites of integration in acutely infected cells with concomitant cell death. There was a single site of integration in chronically infected cells with no cell death. There were more integrated infectious viral DNA molecules per cell in acutely infected cells than in chronically infected cells. These results are consistent with the hypotheses that the cell death in the acute phase of infection is a result of the integration of the infectious viral DNA at multiple sites, and that only those cells survive that have the infectious viral DNA integrated exclusively at the single site."}
{"id": "PMID:203409", "title": "Sterol metabolism. XL. On the failure of superoxide radical anion to react with cholesterol.", "content": "Superoxide radical anion (O-2) failed to react with cholesterol under a variety of conditions. In some instances products indicative of free radical oxidation by molecular oxygen (O2) were found, but no products of electronically excited (singlet) molecular oxygen (1O2) attack on cholesterol were detected. These results do not support a direct role of O-2 in lipid peroxidation of cholesterol-rich membranes or of the formation of 1O2 from O-2 dismutation.", "contents": "Sterol metabolism. XL. On the failure of superoxide radical anion to react with cholesterol. Superoxide radical anion (O-2) failed to react with cholesterol under a variety of conditions. In some instances products indicative of free radical oxidation by molecular oxygen (O2) were found, but no products of electronically excited (singlet) molecular oxygen (1O2) attack on cholesterol were detected. These results do not support a direct role of O-2 in lipid peroxidation of cholesterol-rich membranes or of the formation of 1O2 from O-2 dismutation."}
{"id": "PMID:203410", "title": "[Modeling of neuronal plasticity by studies of spatio-temporal behavior of neural structures].", "content": "In order to point out spatio-temporal filtering of nervous structures after previous studies of their spatial behaviour, we have built a new model of cell according to synaptic and membrane plasticity (it agrees with properties of integration, memory and synaptic fatigue). This model, intended to be produced in many units, is made with integrated circuits in \"thick film\" technology.", "contents": "[Modeling of neuronal plasticity by studies of spatio-temporal behavior of neural structures]. In order to point out spatio-temporal filtering of nervous structures after previous studies of their spatial behaviour, we have built a new model of cell according to synaptic and membrane plasticity (it agrees with properties of integration, memory and synaptic fatigue). This model, intended to be produced in many units, is made with integrated circuits in \"thick film\" technology."}
{"id": "PMID:203411", "title": "[Effect of scorpion venom (Androctonus australis) on neuromuscular transmission inhibited by botulinum toxin in the frog].", "content": "We have shown that Scorpion venom restores the neuro-muscular transmission inhibited by Botulinum toxin in the Frog. The effectiveness of Scorpion venom was antagonized by excess magnesium.", "contents": "[Effect of scorpion venom (Androctonus australis) on neuromuscular transmission inhibited by botulinum toxin in the frog]. We have shown that Scorpion venom restores the neuro-muscular transmission inhibited by Botulinum toxin in the Frog. The effectiveness of Scorpion venom was antagonized by excess magnesium."}
{"id": "PMID:203413", "title": "Assay of vitamins D2 and D3, and 25-hydroxyvitamins D2 and D3 in human plasma by high-performance liquid chromatography.", "content": "I describe a new assay that is capable of measuring vitamin D2, vitamin D3, 25-hydroxyvitamin D2, and 25-hydroxyvitamin D3 in 2 ml of plasma or serum. Plasma is extracted by the Bligh and Dyer technique [Can. J. Biochem. Physiol. 37, 911 (1959)], the lipid component is fractionated by two high-performance liquid-chromatographic systems based upon adsorption and reversed-phase chromatography, and each of the four vitamin D metabolites is measured by its absorbance at 254 nm. The method has a sensitivity limit of 0.5 mug/liter of plasma. The identity of metabolite peaks was confirmed by mass spectrometry, ultraviolet absorption spectrophotometry, and rechromatography, and there was good correlation (r=0.84) between plasma 25-hydroxyvitamin D as measured by the present method and by a protein binding assay developed in our laboratory. Mean concentrations of vitamin D and 25-hydroxyvitamin D in normal adults (n=25) in December were 2.2 +/- 1.1 (SD) and 16 +/- 3.9 (SD) mug/liter, respectively. 25-Hyroxyvitamin D2 made up 31% of the total 25-hydroxyvitamin D. Patients receiving pharmacological doses of vitamin D had values for vitamin D and 25-hydroxyvitamin D that were 10- to 100-fold normal. This method provides a rapid, reliable physico-chemical assay that appears to have advantages over existing protein binding assays and can be used to measure circulating vitamin D.", "contents": "Assay of vitamins D2 and D3, and 25-hydroxyvitamins D2 and D3 in human plasma by high-performance liquid chromatography. I describe a new assay that is capable of measuring vitamin D2, vitamin D3, 25-hydroxyvitamin D2, and 25-hydroxyvitamin D3 in 2 ml of plasma or serum. Plasma is extracted by the Bligh and Dyer technique [Can. J. Biochem. Physiol. 37, 911 (1959)], the lipid component is fractionated by two high-performance liquid-chromatographic systems based upon adsorption and reversed-phase chromatography, and each of the four vitamin D metabolites is measured by its absorbance at 254 nm. The method has a sensitivity limit of 0.5 mug/liter of plasma. The identity of metabolite peaks was confirmed by mass spectrometry, ultraviolet absorption spectrophotometry, and rechromatography, and there was good correlation (r=0.84) between plasma 25-hydroxyvitamin D as measured by the present method and by a protein binding assay developed in our laboratory. Mean concentrations of vitamin D and 25-hydroxyvitamin D in normal adults (n=25) in December were 2.2 +/- 1.1 (SD) and 16 +/- 3.9 (SD) mug/liter, respectively. 25-Hyroxyvitamin D2 made up 31% of the total 25-hydroxyvitamin D. Patients receiving pharmacological doses of vitamin D had values for vitamin D and 25-hydroxyvitamin D that were 10- to 100-fold normal. This method provides a rapid, reliable physico-chemical assay that appears to have advantages over existing protein binding assays and can be used to measure circulating vitamin D."}
{"id": "PMID:203414", "title": "An enzymatic triglyceride method that is suitable for long-term population studies.", "content": "An enzymatic triglyceride method has been shown to be a suitable alternative to the Lipid Research Clinics' extraction/fluorometry method in long-term population studies. Correlation of results obtained with this method by this laboratory (y-axis) and by the Minneapolis Lipid Research Clinic Laboratory (x-axis) during a nine-week standardization period produced a curve with an intercept of -72 mg/liter, a slope of 1.019, and a correlation coefficient of r=0.996 (n=47). During this standardization period certain methodological problems were observed and corrected. An increase in background in certain clinical specimens, caused by spontaneous degradation of NADH, was observed, accurately measured, and taken into account when appropriate.", "contents": "An enzymatic triglyceride method that is suitable for long-term population studies. An enzymatic triglyceride method has been shown to be a suitable alternative to the Lipid Research Clinics' extraction/fluorometry method in long-term population studies. Correlation of results obtained with this method by this laboratory (y-axis) and by the Minneapolis Lipid Research Clinic Laboratory (x-axis) during a nine-week standardization period produced a curve with an intercept of -72 mg/liter, a slope of 1.019, and a correlation coefficient of r=0.996 (n=47). During this standardization period certain methodological problems were observed and corrected. An increase in background in certain clinical specimens, caused by spontaneous degradation of NADH, was observed, accurately measured, and taken into account when appropriate."}
{"id": "PMID:203416", "title": "Vitamin D metabolism.", "content": "During the past decade, an explosion of information has become available on the metabolism and function of vitamin D which is of great importance to clinicians in the treatment of metabolic bone disease. We have learned that vitamin D is the precursor of at least one hormone and that this hormone carries out functions in calcium and phosphorus metabolism bringing about mineralization of bone on one hand, and the prevention of hypocalcaemic tetany on the other. It may also function in the prevention of such degenerative bone diseases as osteoporosis. An important analogue of this hormone, 1alpha-hydroxyvitamin D3 has been prepared and is used successfully in the treatment of a variety of clinical conditions. This presentation will summarize these findings and their possible implications in these metabolic bone diseases.", "contents": "Vitamin D metabolism. During the past decade, an explosion of information has become available on the metabolism and function of vitamin D which is of great importance to clinicians in the treatment of metabolic bone disease. We have learned that vitamin D is the precursor of at least one hormone and that this hormone carries out functions in calcium and phosphorus metabolism bringing about mineralization of bone on one hand, and the prevention of hypocalcaemic tetany on the other. It may also function in the prevention of such degenerative bone diseases as osteoporosis. An important analogue of this hormone, 1alpha-hydroxyvitamin D3 has been prepared and is used successfully in the treatment of a variety of clinical conditions. This presentation will summarize these findings and their possible implications in these metabolic bone diseases."}
{"id": "PMID:203417", "title": "Long-term therapy with 1alpha-hydroxyvitamin D3 in children with 'pseudo-deficiency' rickets.", "content": "This investigation confirms that 1alpha-hydroxyvitamin D3 (1alpha-OHD3) is a potent drug for the treatment of patients with pseudo-deficiency rickets (Balsan et al., 1975a; Reade et al., 1975; Prader et al., 1976). 1alpha-OHD3 corrects their intestinal malabsorption of calcium and phosphorus, normalizes their serum calcium and phosphate concentrations and promotes healing of skeletal lesions. This study also shows differences in the needs for 1alpha-OHD3 of children with PDR. Three factors appear to be of importance: familial sensitivity, severity of chronic secondary hyperparathyroidism, and periods of increased growth velocity. Tolerance to long-term 1alpha-OHD3 therapy, at doses varying from 0.5 to 2 microgram/d is excellent. Surveillance of patients should include regular measurements of 24 h urinary excretion of calcium, since hypercalciuria is the first signal of overdosage.", "contents": "Long-term therapy with 1alpha-hydroxyvitamin D3 in children with 'pseudo-deficiency' rickets. This investigation confirms that 1alpha-hydroxyvitamin D3 (1alpha-OHD3) is a potent drug for the treatment of patients with pseudo-deficiency rickets (Balsan et al., 1975a; Reade et al., 1975; Prader et al., 1976). 1alpha-OHD3 corrects their intestinal malabsorption of calcium and phosphorus, normalizes their serum calcium and phosphate concentrations and promotes healing of skeletal lesions. This study also shows differences in the needs for 1alpha-OHD3 of children with PDR. Three factors appear to be of importance: familial sensitivity, severity of chronic secondary hyperparathyroidism, and periods of increased growth velocity. Tolerance to long-term 1alpha-OHD3 therapy, at doses varying from 0.5 to 2 microgram/d is excellent. Surveillance of patients should include regular measurements of 24 h urinary excretion of calcium, since hypercalciuria is the first signal of overdosage."}
{"id": "PMID:203418", "title": "Vitamin D resistant hypophosphataemic osteomalacia: treatment with 1alpha-hydroxyvitamin D3.", "content": "Ten patients with vitamin D resistant hypophosphataemic osteomalacia are described. They had hypophosphataemia with a decreased tubular reabsorption of phosphate, malabsorption of calcium and phosphorus, proximal myopathy and extensive osteomalacic changes on iliac crest bone biopsy. The plasma alkaline phosphatase and urine hydroxyproline, however, were raised in only some of the patients. Treatment with 1alpha-hydroxyvitamin D3 in high doses rapidly cured the myopathy, increased calcium and phosphorus absorption and retention and healed the osteomalacia. Phosphorus supplements were not required.", "contents": "Vitamin D resistant hypophosphataemic osteomalacia: treatment with 1alpha-hydroxyvitamin D3. Ten patients with vitamin D resistant hypophosphataemic osteomalacia are described. They had hypophosphataemia with a decreased tubular reabsorption of phosphate, malabsorption of calcium and phosphorus, proximal myopathy and extensive osteomalacic changes on iliac crest bone biopsy. The plasma alkaline phosphatase and urine hydroxyproline, however, were raised in only some of the patients. Treatment with 1alpha-hydroxyvitamin D3 in high doses rapidly cured the myopathy, increased calcium and phosphorus absorption and retention and healed the osteomalacia. Phosphorus supplements were not required."}
{"id": "PMID:203419", "title": "1alpha-hydroxyvitamin D3 in the treatment of nutritional and metabolic rickets and osteomalacia.", "content": "Five patients with nutritional osteomalacia or rickets and six children with rickets unresponsive to physiological doses of vitamin D were treated with 1alpha-hydroxyvitamin D3 (1alpha-OHD3). Patients with nutritional osteomalacia responded to 1--2 microgram/day of 1alpha-OHD3. The most striking findings were rises in plasma calcium and, in one case, a decrease in faecal calcium. In some cases there was a rise in plasma phosphorus, alkaline phosphatase remained unchanged. There was radiological healing. In three patients with cystinosis and one with hypophosphataemia and Barrter's syndrome 2 microgram of 1alpha-OHD3 produced healing of rickets. Plasma phosphate rose on treatment, possibly by a suppression of parathyroid activity. The response to such low doses of 1alpha-OHD3 suggests impaired 1alpha-hydroxylation of 25-hydroxyvitamin D in these patients. A patient with intestinal malabsorption was resistant to high doses of 1alpha-OHD3 by mouth but responded to parenteral administration. A boy with osteopetrosis and the biochemical changes of rickets was resistant to large doses of 1alpha-OHD3 presumably because of failure of osseous response.", "contents": "1alpha-hydroxyvitamin D3 in the treatment of nutritional and metabolic rickets and osteomalacia. Five patients with nutritional osteomalacia or rickets and six children with rickets unresponsive to physiological doses of vitamin D were treated with 1alpha-hydroxyvitamin D3 (1alpha-OHD3). Patients with nutritional osteomalacia responded to 1--2 microgram/day of 1alpha-OHD3. The most striking findings were rises in plasma calcium and, in one case, a decrease in faecal calcium. In some cases there was a rise in plasma phosphorus, alkaline phosphatase remained unchanged. There was radiological healing. In three patients with cystinosis and one with hypophosphataemia and Barrter's syndrome 2 microgram of 1alpha-OHD3 produced healing of rickets. Plasma phosphate rose on treatment, possibly by a suppression of parathyroid activity. The response to such low doses of 1alpha-OHD3 suggests impaired 1alpha-hydroxylation of 25-hydroxyvitamin D in these patients. A patient with intestinal malabsorption was resistant to high doses of 1alpha-OHD3 by mouth but responded to parenteral administration. A boy with osteopetrosis and the biochemical changes of rickets was resistant to large doses of 1alpha-OHD3 presumably because of failure of osseous response."}
{"id": "PMID:203421", "title": "An unusual form of galactosemia: studies on erythrocytes and hair roots.", "content": "An unusual form of galactosemia is described in a 7-month-old boy, characterized by a late onset of the clinical symptoms. A high apparent residual activity of erythrocyte galactose-1-phosphate uridyl transferase (GT) was measured with the spectrophotometric UDP-Glucose consumption test(+/-25% of normal). The residual activity in erythrocyte lysates, determined when the patient was 7, 16 and 22 months old, significantly decreased upon storage and after preincubation with NAD-ase. The radiochemical measurement of GT activity demonstrated a severe deficiency: only a level of +/-1% of normal activity was observed, and no effects of storage or NAD-ase could be demonstrated. GT and galactokinase (GK) activities were measured radiochemically in lysates from hair roots obtained from the human scalp, and it was found that the GT/GK activity ratio is a useful index for the detection of heterozygotes. Erythrocyte and hair root lysates from the heterozygous parents of the patient displayed GT/GK ratios which were intermediate between mutant and normal. Because they offer a simple and fast way to obtain biopsy material, hair roots might become of increasing importance for carrier detection studies.", "contents": "An unusual form of galactosemia: studies on erythrocytes and hair roots. An unusual form of galactosemia is described in a 7-month-old boy, characterized by a late onset of the clinical symptoms. A high apparent residual activity of erythrocyte galactose-1-phosphate uridyl transferase (GT) was measured with the spectrophotometric UDP-Glucose consumption test(+/-25% of normal). The residual activity in erythrocyte lysates, determined when the patient was 7, 16 and 22 months old, significantly decreased upon storage and after preincubation with NAD-ase. The radiochemical measurement of GT activity demonstrated a severe deficiency: only a level of +/-1% of normal activity was observed, and no effects of storage or NAD-ase could be demonstrated. GT and galactokinase (GK) activities were measured radiochemically in lysates from hair roots obtained from the human scalp, and it was found that the GT/GK activity ratio is a useful index for the detection of heterozygotes. Erythrocyte and hair root lysates from the heterozygous parents of the patient displayed GT/GK ratios which were intermediate between mutant and normal. Because they offer a simple and fast way to obtain biopsy material, hair roots might become of increasing importance for carrier detection studies."}
{"id": "PMID:203422", "title": "Double pre-beta lipoprotein in ischaemic heart disease.", "content": "The presence or absence of a double pre-beta lipoprotein (pre-beta 1+ or pre-beta 1-) peak on agarose gel electrophoresis was recorded in: a) 77 survivors of myocardial infarction, b) their first-degree relatives, and c) 148 controls. Thirty-nine percent of myocardial infarction survivors and 24% of controls had pre-beta 1+ (P less than 0.05). The segregation of pre-beta 1+ in the families of myocardial infarction survivors was consistent with autosomal dominant inheritance. In the control group, fasting serum cholesterol and triglyceride values were higher in the pre beta 1+ subjects, but the differences were not significant. We conclude that the presence of double pre-beta lipoprotein peak on electrophoresis is associated with an increased risk of myocardial infarction.", "contents": "Double pre-beta lipoprotein in ischaemic heart disease. The presence or absence of a double pre-beta lipoprotein (pre-beta 1+ or pre-beta 1-) peak on agarose gel electrophoresis was recorded in: a) 77 survivors of myocardial infarction, b) their first-degree relatives, and c) 148 controls. Thirty-nine percent of myocardial infarction survivors and 24% of controls had pre-beta 1+ (P less than 0.05). The segregation of pre-beta 1+ in the families of myocardial infarction survivors was consistent with autosomal dominant inheritance. In the control group, fasting serum cholesterol and triglyceride values were higher in the pre beta 1+ subjects, but the differences were not significant. We conclude that the presence of double pre-beta lipoprotein peak on electrophoresis is associated with an increased risk of myocardial infarction."}
{"id": "PMID:203423", "title": "Blastogenic response of human lymphocytes to human cytomegalovirus.", "content": "A method was developed for measuring the blastogenic response of human lymphocytes to human cytomegalovirus (CMV). Viral and control antigens were prepared by extracting disrupted infected and uninfected cell cultures with an alkaline buffer. Lymphocytes from ten donors with complement-fixing (CF) antibody exhibited a blastogenic response, whereas cells from ten seronegative donors did not. A relationship between the stimulation index (SI) and the results of neutralization (NT), indirect haemagglutination (IHA) or CF tests was not observed. The maximum blastogenic response occurred after 5 to 7 days of incubation and was usually greater when the cultures were supplemented with homologous plasma instead of sera. The presence of CMV antibody in the supplementary sera did not appear to affect the reactivity of the lymphocytes.", "contents": "Blastogenic response of human lymphocytes to human cytomegalovirus. A method was developed for measuring the blastogenic response of human lymphocytes to human cytomegalovirus (CMV). Viral and control antigens were prepared by extracting disrupted infected and uninfected cell cultures with an alkaline buffer. Lymphocytes from ten donors with complement-fixing (CF) antibody exhibited a blastogenic response, whereas cells from ten seronegative donors did not. A relationship between the stimulation index (SI) and the results of neutralization (NT), indirect haemagglutination (IHA) or CF tests was not observed. The maximum blastogenic response occurred after 5 to 7 days of incubation and was usually greater when the cultures were supplemented with homologous plasma instead of sera. The presence of CMV antibody in the supplementary sera did not appear to affect the reactivity of the lymphocytes."}
{"id": "PMID:203424", "title": "Immunosuppressive effects of lymphocyte (type II) and leucocyte (type I) interferon on primary antibody responses in vivo and in vitro.", "content": "We have tested the hypothesis that type II interferon (IF), released by immune lymphocytes after in vivo stimulation with tuberculin, has immunosuppressive effects. Mycobacterium bovis (BCG) infected mice injected with tuberculin showed a very intense suppression of antibody response to sheep erythrocytes. Sera containing lymphocyte IF strongly inhibited primary immune responses to sheep erythrocytes in cultures. Addition of macrophages could not counteract the in vitro immunosuppressive effects of lymphocyte IF, suggesting that the main effect is exerted directly on lymphocytes. Sendai virus-induced leucocyte (type I) IF was also shown to have suppressive effects in vivo and in vitro. However, lymphocyte IF was shown to be much more immunosuppressive than a preparation of type I interferon with equivalent antiviral potency. Thus type II IF, as a product of activated lymphocytes, may have a major immunoregulatory role.", "contents": "Immunosuppressive effects of lymphocyte (type II) and leucocyte (type I) interferon on primary antibody responses in vivo and in vitro. We have tested the hypothesis that type II interferon (IF), released by immune lymphocytes after in vivo stimulation with tuberculin, has immunosuppressive effects. Mycobacterium bovis (BCG) infected mice injected with tuberculin showed a very intense suppression of antibody response to sheep erythrocytes. Sera containing lymphocyte IF strongly inhibited primary immune responses to sheep erythrocytes in cultures. Addition of macrophages could not counteract the in vitro immunosuppressive effects of lymphocyte IF, suggesting that the main effect is exerted directly on lymphocytes. Sendai virus-induced leucocyte (type I) IF was also shown to have suppressive effects in vivo and in vitro. However, lymphocyte IF was shown to be much more immunosuppressive than a preparation of type I interferon with equivalent antiviral potency. Thus type II IF, as a product of activated lymphocytes, may have a major immunoregulatory role."}
{"id": "PMID:203425", "title": "Protective activity of secondary effector T cells generated in vitro against ectromelia virus infection in vivo.", "content": "The anti-viral activity of secondary effector cells generated in vitro against ectromelia virus infection was investigated. Depending upon the order of administration of cells and virus, 2 X 10(6) cells significantly reduce virus titres in recipient mice. Mice injected with lymphocytic choriomeningitis (LCM) virus are not protected by secondary effector cells against ectromelia virus infection and vice versa. The cells conferring anti-viral activity are sensitive to anti-theta and complement treatment, and must share H-2K or H-2D region genes with the recipients in order for significant reduction of virus titres to occur. The possibility of exploiting this approach in clinical medicine by using T cell-mediated mechanisms against certain viral infections is briefly discussed.", "contents": "Protective activity of secondary effector T cells generated in vitro against ectromelia virus infection in vivo. The anti-viral activity of secondary effector cells generated in vitro against ectromelia virus infection was investigated. Depending upon the order of administration of cells and virus, 2 X 10(6) cells significantly reduce virus titres in recipient mice. Mice injected with lymphocytic choriomeningitis (LCM) virus are not protected by secondary effector cells against ectromelia virus infection and vice versa. The cells conferring anti-viral activity are sensitive to anti-theta and complement treatment, and must share H-2K or H-2D region genes with the recipients in order for significant reduction of virus titres to occur. The possibility of exploiting this approach in clinical medicine by using T cell-mediated mechanisms against certain viral infections is briefly discussed."}
{"id": "PMID:203426", "title": "Blastogenic response of purified human T-lymphocyte populations to Epstein-Barr virus (EBV).", "content": "The blastogenic response of T-cell populations to infectious EBV (B95-8 strain) was studied. The addition of virus increased the [3H]thymidine uptake of unfractionated lymphocytes from seropositive and seronegative subjects, and from cord blood, but not from patients with infectious mononucleosis. The same amount of virus evoked a small response in purified T cells from seropositive donors, but not in T cells from the other sources. The addition of autologous B lymphocytes with EBV adsorbed on their surfaces caused a more significant blastogenic response, which was even more pronounced in the presence of mercaptoethanol.", "contents": "Blastogenic response of purified human T-lymphocyte populations to Epstein-Barr virus (EBV). The blastogenic response of T-cell populations to infectious EBV (B95-8 strain) was studied. The addition of virus increased the [3H]thymidine uptake of unfractionated lymphocytes from seropositive and seronegative subjects, and from cord blood, but not from patients with infectious mononucleosis. The same amount of virus evoked a small response in purified T cells from seropositive donors, but not in T cells from the other sources. The addition of autologous B lymphocytes with EBV adsorbed on their surfaces caused a more significant blastogenic response, which was even more pronounced in the presence of mercaptoethanol."}
{"id": "PMID:203427", "title": "Molecular exclusion electrophoresis of human serum lipoproteins: patterns in control and ischaemic heart-disease populations.", "content": "1. Electrophoresis of pre-stained lipoproteins on acrylamide-gel gradients has been carried out on serum from populations of control subjects and patients with ischaemic heart disease. The technique resolves components intermediate in position and, by inference, in size, between very-low-density and low-density lipoproteins. 2. These central band components were found in 37% of a control population but the incidence varied with age and sex, being lowest in young males and highest in elderly males. 3. The incidence of central band components in patients with ischaemic heart disease was 64% (males) and 71% (females), and the difference between these figures and those for matched control subjects was highly significant. The intensity of central band components in the group with ischaemic heart disease was significantly greater than in the control group. 4. The presence and intensity of central bands show positive correlation with serum cholesterol and triglyceride values, but many patients showing the phenomenon have normal lipid values. Of patients with ischaemic heart disease 31% showed central band components and had normal lipid values.", "contents": "Molecular exclusion electrophoresis of human serum lipoproteins: patterns in control and ischaemic heart-disease populations. 1. Electrophoresis of pre-stained lipoproteins on acrylamide-gel gradients has been carried out on serum from populations of control subjects and patients with ischaemic heart disease. The technique resolves components intermediate in position and, by inference, in size, between very-low-density and low-density lipoproteins. 2. These central band components were found in 37% of a control population but the incidence varied with age and sex, being lowest in young males and highest in elderly males. 3. The incidence of central band components in patients with ischaemic heart disease was 64% (males) and 71% (females), and the difference between these figures and those for matched control subjects was highly significant. The intensity of central band components in the group with ischaemic heart disease was significantly greater than in the control group. 4. The presence and intensity of central bands show positive correlation with serum cholesterol and triglyceride values, but many patients showing the phenomenon have normal lipid values. Of patients with ischaemic heart disease 31% showed central band components and had normal lipid values."}
{"id": "PMID:203432", "title": "Cutaneous pain without tumor: a manifestation of occult synovioma.", "content": "A thirty-four year old male presented with severe spot tenderness for eighteen months, situated in the right upper anterior thigh. The skin was normal. No tumor, swelling, or inflammation was found. On the basis of a clinical diagnosis of glomus tumor, the area was biopsied and a microscopic synovioma was documented in the fascia just deep to the subcutis. From the literature, it is apparent that approximately 20 percent of the patients with this cancer go through a pretumor phase characterized by only sustained pain or tenderness. By detecting the lesion in this phase, the dermatologist can contribute substantially to an increased cure rate, which has lingered at about 50 percent for at least ten years.", "contents": "Cutaneous pain without tumor: a manifestation of occult synovioma. A thirty-four year old male presented with severe spot tenderness for eighteen months, situated in the right upper anterior thigh. The skin was normal. No tumor, swelling, or inflammation was found. On the basis of a clinical diagnosis of glomus tumor, the area was biopsied and a microscopic synovioma was documented in the fascia just deep to the subcutis. From the literature, it is apparent that approximately 20 percent of the patients with this cancer go through a pretumor phase characterized by only sustained pain or tenderness. By detecting the lesion in this phase, the dermatologist can contribute substantially to an increased cure rate, which has lingered at about 50 percent for at least ten years."}
{"id": "PMID:203433", "title": "Biopsy of the nail area.", "content": "It is as simple to biopsy around the nail as it is at any other site, and there are multiple lesions that deserve biopsy. Biopsy of the nail bed or nail matrix is avoided unless there is possible malignant change. Biopsy sites in the nail bed usually heal satisfactorily, but biopsy of the matrix is more likely to produce permanent deformity.", "contents": "Biopsy of the nail area. It is as simple to biopsy around the nail as it is at any other site, and there are multiple lesions that deserve biopsy. Biopsy of the nail bed or nail matrix is avoided unless there is possible malignant change. Biopsy sites in the nail bed usually heal satisfactorily, but biopsy of the matrix is more likely to produce permanent deformity."}
{"id": "PMID:203434", "title": "Therapy of parotid tumors.", "content": "A therapy schedule is presented for the surgical treatment of parotid tumors, based on the experience gained from more than 600 operations for parotid tumors. The individual surgical techniques (lateral parotidectomy, total parotidectomy with preservation or resection of the facial nerve, with or without reconstruction of the nerve) are selected depending on the histologic findings in the tumors. The fact is stressed that in a tumor disease the lateral parotidectomy constitutes the minimal operation. The different tumors can be divided into four groups. The operative treatment of tumors of the facial nerve in its extratemporal course is particularly mentioned since clinically these growths usually appear to be parotid tumors.", "contents": "Therapy of parotid tumors. A therapy schedule is presented for the surgical treatment of parotid tumors, based on the experience gained from more than 600 operations for parotid tumors. The individual surgical techniques (lateral parotidectomy, total parotidectomy with preservation or resection of the facial nerve, with or without reconstruction of the nerve) are selected depending on the histologic findings in the tumors. The fact is stressed that in a tumor disease the lateral parotidectomy constitutes the minimal operation. The different tumors can be divided into four groups. The operative treatment of tumors of the facial nerve in its extratemporal course is particularly mentioned since clinically these growths usually appear to be parotid tumors."}
{"id": "PMID:203438", "title": "[Ectopic production of chorionic gonadotropin in apudomas (author's transl)].", "content": "Two pheochromocytomas, two carcinoid tumours of the ileum and one pancreatic vipoma showed APUD-system properties and formed electron-dense secretory granules indicating synthesis and storage of proteohormones. Besides catecholamines, 5-hydroxytryptamine and vasoactive intestinal polypeptide, all five tumours contained immunoreactive chorionic gonadotropin and also its free, protomeric beta chain as a sign of de-differentiation. Plasma of the tumour patients also contained immunoreactive chorionic gonadotropin and the free protomeric beta chain, both of which are useful tumour markers.", "contents": "[Ectopic production of chorionic gonadotropin in apudomas (author's transl)]. Two pheochromocytomas, two carcinoid tumours of the ileum and one pancreatic vipoma showed APUD-system properties and formed electron-dense secretory granules indicating synthesis and storage of proteohormones. Besides catecholamines, 5-hydroxytryptamine and vasoactive intestinal polypeptide, all five tumours contained immunoreactive chorionic gonadotropin and also its free, protomeric beta chain as a sign of de-differentiation. Plasma of the tumour patients also contained immunoreactive chorionic gonadotropin and the free protomeric beta chain, both of which are useful tumour markers."}
{"id": "PMID:203439", "title": "[Cerebral damage and cytomegalovirus infection (author's transl)].", "content": "Serological tests were performed on 58 children with microcephalus and 223 children with cerebral damage but no microcephalus (all patients were living in the Munich region). In the microcephalus group 38% had antibodies against cytomegalovirus, while in healthy controls the incidence was only 18%. Mean titre levels were significantly higher in microcephalic children. Of eleven microcephalic children seven were cytomegalovirus excreters: all of the latter had severe cerebral defects. On the other hand, in patients with cerebral damage but no microcephaly there was no difference serologically or with regard to virus excretion from healthy controls. The authors suggest, in conformity with opinions expressed by others, that there is a definite connection between--usually unrecognised--cytometalovirus infection and certain forms of cerebral damage. They may be atypical and symptom-poor diseases in which CNS signs appear only in the course of time.", "contents": "[Cerebral damage and cytomegalovirus infection (author's transl)]. Serological tests were performed on 58 children with microcephalus and 223 children with cerebral damage but no microcephalus (all patients were living in the Munich region). In the microcephalus group 38% had antibodies against cytomegalovirus, while in healthy controls the incidence was only 18%. Mean titre levels were significantly higher in microcephalic children. Of eleven microcephalic children seven were cytomegalovirus excreters: all of the latter had severe cerebral defects. On the other hand, in patients with cerebral damage but no microcephaly there was no difference serologically or with regard to virus excretion from healthy controls. The authors suggest, in conformity with opinions expressed by others, that there is a definite connection between--usually unrecognised--cytometalovirus infection and certain forms of cerebral damage. They may be atypical and symptom-poor diseases in which CNS signs appear only in the course of time."}
{"id": "PMID:203441", "title": "Metabolic effects of some antibilharzial drugs inhibition of citrate oxidation by Bilharcid.", "content": "Bilharcid inhibited citrate oxidation and the inhibition was decreased by time. The inhibition is not restored or reduced by increasing citrate concentration. NAD stimulated citrate oxidation in the presence of Bilharcid. Cysteine slightly stimulated citrate oxidation, while ATP had no effect. Addition of citrate before Bilharcid protected the enzyme against the inhibitory action of the drug.", "contents": "Metabolic effects of some antibilharzial drugs inhibition of citrate oxidation by Bilharcid. Bilharcid inhibited citrate oxidation and the inhibition was decreased by time. The inhibition is not restored or reduced by increasing citrate concentration. NAD stimulated citrate oxidation in the presence of Bilharcid. Cysteine slightly stimulated citrate oxidation, while ATP had no effect. Addition of citrate before Bilharcid protected the enzyme against the inhibitory action of the drug."}
{"id": "PMID:203448", "title": "PCBs and environmental contamination.", "content": "A survey is given on reported PCB-residues and accumulation in various environmental media including water and aquatic environment, flora, animals, food, and humans. Model studies with technical PCB, as well as with pure individual components, are presented from various working groups. As examples, metabolic studies and photochemical experiments are discussed. According to our present knowledge, a major metabolic pathway in animals and plants is hydroxylation, often followed by methylation or conjugation. By UV-irradiation, however, oxygenation, dechlorination and chlorination, polymerization and isomerization may occur.", "contents": "PCBs and environmental contamination. A survey is given on reported PCB-residues and accumulation in various environmental media including water and aquatic environment, flora, animals, food, and humans. Model studies with technical PCB, as well as with pure individual components, are presented from various working groups. As examples, metabolic studies and photochemical experiments are discussed. According to our present knowledge, a major metabolic pathway in animals and plants is hydroxylation, often followed by methylation or conjugation. By UV-irradiation, however, oxygenation, dechlorination and chlorination, polymerization and isomerization may occur."}
{"id": "PMID:203449", "title": "Overproduction disease in man due to enzyme feedback resistance mutation. Purine overproduction in gout due to excessive activity of mutant feedback-resistant phosphoribosylpyrophosphate synthetase.", "content": "Physiologically superactive phosphoribosylpyrophosphate (PRPP) synthetase, due to feedback resistance mutation, was found in a family with excessive purine production, gout and uric acid lithiasis. The superactivity of the mutant enzyme was manifest in the propositus' erythrocytes and cultured fibroblasts, in increased generation, content and metabolic availability of PRPP, leading in the fibroblasts to acceleration of the rate of purine synthesis de novo. One of the propositus' two siblings was similarly affected, but the propositus' father, his second brother and four sons, were all clinically and biochemically normal. The mother was clinically normal and normouricemic, but hyperuricosuric. Cultured fibroblasts from her skin exhibited variability in PRPP content and availability and in the rate of purine synthesis de novo. The mother's cultures were found to contain a mosaicism of two cell populations, one with normal and the other with mutant PRPP synthetase, indicating an X-linked pattern of inheritance of the PRPP synthetase abnormality in this gouty family.", "contents": "Overproduction disease in man due to enzyme feedback resistance mutation. Purine overproduction in gout due to excessive activity of mutant feedback-resistant phosphoribosylpyrophosphate synthetase. Physiologically superactive phosphoribosylpyrophosphate (PRPP) synthetase, due to feedback resistance mutation, was found in a family with excessive purine production, gout and uric acid lithiasis. The superactivity of the mutant enzyme was manifest in the propositus' erythrocytes and cultured fibroblasts, in increased generation, content and metabolic availability of PRPP, leading in the fibroblasts to acceleration of the rate of purine synthesis de novo. One of the propositus' two siblings was similarly affected, but the propositus' father, his second brother and four sons, were all clinically and biochemically normal. The mother was clinically normal and normouricemic, but hyperuricosuric. Cultured fibroblasts from her skin exhibited variability in PRPP content and availability and in the rate of purine synthesis de novo. The mother's cultures were found to contain a mosaicism of two cell populations, one with normal and the other with mutant PRPP synthetase, indicating an X-linked pattern of inheritance of the PRPP synthetase abnormality in this gouty family."}
{"id": "PMID:203450", "title": "The effects of fasting on glucose-6-phosphatase of mouse liver and kidney.", "content": "Glucose-6-phosphatase levels were measured in livers and kidneys of control mice and mice fasted for 24, 48, and 72 h, respectively. The enzyme was assayed with and without deoxycholate supplementation. When assayed in the absence of deoxycholate, significant increases in liver enzyme levels was observed after fasting for 48 and 72 h, respectively. For the kidney enzyme, a significant increase was observed only after 48 h fasting. When the enzyme was assayed in the presence of 4.8 mmol/l deoxycholate, fasting-induced increases of liver enzyme levels were further potentiated, but no significant differences were observed in kidney enzyme levels between fasted and control mice.", "contents": "The effects of fasting on glucose-6-phosphatase of mouse liver and kidney. Glucose-6-phosphatase levels were measured in livers and kidneys of control mice and mice fasted for 24, 48, and 72 h, respectively. The enzyme was assayed with and without deoxycholate supplementation. When assayed in the absence of deoxycholate, significant increases in liver enzyme levels was observed after fasting for 48 and 72 h, respectively. For the kidney enzyme, a significant increase was observed only after 48 h fasting. When the enzyme was assayed in the presence of 4.8 mmol/l deoxycholate, fasting-induced increases of liver enzyme levels were further potentiated, but no significant differences were observed in kidney enzyme levels between fasted and control mice."}
{"id": "PMID:203451", "title": "Evidence for the participation of cytosolic protein kinases in membrane phosphorylation in intact erythrocytes.", "content": "The effects of adenosine 3':5'-monophosphate (cyclic AMP) on the phosphorylation of membrane proteins in intact rabbit and human erythrocytes were investigated. The addition of cyclic AMP to intact human or rabbit erythrocytes results in an increase in the incorporation of ortho[32P]phosphate into several membrane protein components which are known to serve as substrates for the cyclic-AMP-dependent protein kinases. Thus this increase in protein phsophorylation is probably due to the activation of either soluble or membrane-bound cyclic-AMP-dependent protein kinases. Incubation of human erythrocytes in the presence of ortho [32P]phosphate and cyclic AMP also leads to the phosphorylation of a membrane protein component, band 7, which has not been previously detected in the autophosphorylation of isolated ghosts. Since rabbit erythrocyte membranes do not contain any cyclic-AMP-dependent protein kinase, the results suggest that cytoplasmic kinases also play a role in the phosphorylation of membrane proteins in intact cells.", "contents": "Evidence for the participation of cytosolic protein kinases in membrane phosphorylation in intact erythrocytes. The effects of adenosine 3':5'-monophosphate (cyclic AMP) on the phosphorylation of membrane proteins in intact rabbit and human erythrocytes were investigated. The addition of cyclic AMP to intact human or rabbit erythrocytes results in an increase in the incorporation of ortho[32P]phosphate into several membrane protein components which are known to serve as substrates for the cyclic-AMP-dependent protein kinases. Thus this increase in protein phsophorylation is probably due to the activation of either soluble or membrane-bound cyclic-AMP-dependent protein kinases. Incubation of human erythrocytes in the presence of ortho [32P]phosphate and cyclic AMP also leads to the phosphorylation of a membrane protein component, band 7, which has not been previously detected in the autophosphorylation of isolated ghosts. Since rabbit erythrocyte membranes do not contain any cyclic-AMP-dependent protein kinase, the results suggest that cytoplasmic kinases also play a role in the phosphorylation of membrane proteins in intact cells."}
{"id": "PMID:203454", "title": "A universal lipid exchange protein from rat hepatoma.", "content": "The postmicrosomal protein fraction from rat hepatoma 27 adjusted to pH 5.1 stimulates phospholipid exchange between rat liver microsomes and mitochondria with higher rates and in a less specific way than the corresponding fraction from rat liver. A phospholipid exchange protein has been purified to homogeneity from the hepatoma pH-5.1 supernatant by gel filtration on Sephadex G-75 and ion-exchange chromatography on carboxymethylcellulose. The isolated protein had a molecular weight of 11200 as determined by electrophoresis on polyacrylamide in the presence of dodecyl sulfate and of 11168 as calculated from the amino acid composition. Isoelectric focusing showed a single band at pH 5.2. in the assay system rat liver microsomes leads to mitochondria the protein exhibits a complete lack of substrate specificity transferring all the major microsomal phospholipids to about the same extent. The possible role of the isolated phospholipid exchange protein in the chemical dedifferentiation of hepatoma cell membranes is discussed.", "contents": "A universal lipid exchange protein from rat hepatoma. The postmicrosomal protein fraction from rat hepatoma 27 adjusted to pH 5.1 stimulates phospholipid exchange between rat liver microsomes and mitochondria with higher rates and in a less specific way than the corresponding fraction from rat liver. A phospholipid exchange protein has been purified to homogeneity from the hepatoma pH-5.1 supernatant by gel filtration on Sephadex G-75 and ion-exchange chromatography on carboxymethylcellulose. The isolated protein had a molecular weight of 11200 as determined by electrophoresis on polyacrylamide in the presence of dodecyl sulfate and of 11168 as calculated from the amino acid composition. Isoelectric focusing showed a single band at pH 5.2. in the assay system rat liver microsomes leads to mitochondria the protein exhibits a complete lack of substrate specificity transferring all the major microsomal phospholipids to about the same extent. The possible role of the isolated phospholipid exchange protein in the chemical dedifferentiation of hepatoma cell membranes is discussed."}
{"id": "PMID:203455", "title": "A hydrogen-deuterium exchange study of the amide protons of polymyxin B by nuclear-magnetic-resonance spectroscopy.", "content": "1. Proton magnetic resonance spectra at 270 MHz of polymyxin B, a cationic oligopeptide antibiotic, show the influence of the inorganic counteranion present in solution. 2. Hydrogen-deuterium exchange rates for the amide protons are of two types, depending on whether the anion is monovalent or polyvalent. Polyvalent anions catalyse the acid-catalysed reaction more than the monovalent anions. 3. The structure in solution was monitored using the proton signals of the amides, the phenylalanine aromatic protons, and the leucine methyl and gamma-CH protons in several polymyxin salts. The temperature coefficients of the chemical shifts of the N-H protons are used to identify two beta turns in the cyclic ring of polymyxin B. The variation in chemical shift of the N-H protons, the aromatic protons and the leucine protons are correlated with anionic size and electronegativity.", "contents": "A hydrogen-deuterium exchange study of the amide protons of polymyxin B by nuclear-magnetic-resonance spectroscopy. 1. Proton magnetic resonance spectra at 270 MHz of polymyxin B, a cationic oligopeptide antibiotic, show the influence of the inorganic counteranion present in solution. 2. Hydrogen-deuterium exchange rates for the amide protons are of two types, depending on whether the anion is monovalent or polyvalent. Polyvalent anions catalyse the acid-catalysed reaction more than the monovalent anions. 3. The structure in solution was monitored using the proton signals of the amides, the phenylalanine aromatic protons, and the leucine methyl and gamma-CH protons in several polymyxin salts. The temperature coefficients of the chemical shifts of the N-H protons are used to identify two beta turns in the cyclic ring of polymyxin B. The variation in chemical shift of the N-H protons, the aromatic protons and the leucine protons are correlated with anionic size and electronegativity."}
{"id": "PMID:203459", "title": "Quantitative studies on competitive ligand binding to bovine serum albumin by use of the spin label 5-doxyl dodecanoic acid.", "content": "The binding of the spin label 5-doxyl dodecanoic acid to bovine serum albumin in phosphate buffer at pH 7.4 was studied by electron spin resonance spectroscopy. Free label and label bound to serum albumin could be quantitatively measured and evaluated from the superposition spectra of these two species with no previous separation. The efficiency relative to the spin label as competitors for binding to serum albumin was studied with salicylic acid and some fatty acids of medium length. The results were represented both by the stoichiometric model involving equilibrium constants Ki, by binding isotherms constructed from the Ki values, and by a purely graphical representation of the experimental data points without connection with any special binding model.", "contents": "Quantitative studies on competitive ligand binding to bovine serum albumin by use of the spin label 5-doxyl dodecanoic acid. The binding of the spin label 5-doxyl dodecanoic acid to bovine serum albumin in phosphate buffer at pH 7.4 was studied by electron spin resonance spectroscopy. Free label and label bound to serum albumin could be quantitatively measured and evaluated from the superposition spectra of these two species with no previous separation. The efficiency relative to the spin label as competitors for binding to serum albumin was studied with salicylic acid and some fatty acids of medium length. The results were represented both by the stoichiometric model involving equilibrium constants Ki, by binding isotherms constructed from the Ki values, and by a purely graphical representation of the experimental data points without connection with any special binding model."}
{"id": "PMID:203460", "title": "Calf-spleen nicotinamide-adenine dinucleotide glycohydrolase. Properties of the active site.", "content": "The interaction between the nicotinamide adenine dinucleotide binding domain of calf spleen NAD glycohydrolase and its ligands has been studied. The use of competitive inhibitors, structurally related to different portions of the NAD molecule (i.e. adenosine and nicotinamide moieties), revealed the considerable importance of the binding between the pyrophosphate linkage and probably an arginyl residue of the active site. This interaction allows the positioning of the substrate in a conformation which permits catalysis to occur. The binding between the 2'-hydroxyl of the adenosine moiety and a residue of the active site, which exists in NAD-linked dehydrogenases, is probably missing in the calf spleen NAD glycohydrolase, based on the inhibition by salicylates, 2'-deoxyadenosine 5'-monophosphate and the hydrolysis of the 2'-deoxyadenosine analogue of NAD. The NAD glycohydrolase could be completely inactivated by 2,3-butanedione, an arginyl-modifying reagent. The reaction followed pseudo-first-order kinetics and the modification was found to be reversible. Woodward's reagent K, a reagent for carboxyl residues, partially inactivated the enzyme, which resulted in a change of the NAD glycohydrolase kinetic parameters Km and V. The inactivation rate was complicated by a parallel decomposition of the reagent.", "contents": "Calf-spleen nicotinamide-adenine dinucleotide glycohydrolase. Properties of the active site. The interaction between the nicotinamide adenine dinucleotide binding domain of calf spleen NAD glycohydrolase and its ligands has been studied. The use of competitive inhibitors, structurally related to different portions of the NAD molecule (i.e. adenosine and nicotinamide moieties), revealed the considerable importance of the binding between the pyrophosphate linkage and probably an arginyl residue of the active site. This interaction allows the positioning of the substrate in a conformation which permits catalysis to occur. The binding between the 2'-hydroxyl of the adenosine moiety and a residue of the active site, which exists in NAD-linked dehydrogenases, is probably missing in the calf spleen NAD glycohydrolase, based on the inhibition by salicylates, 2'-deoxyadenosine 5'-monophosphate and the hydrolysis of the 2'-deoxyadenosine analogue of NAD. The NAD glycohydrolase could be completely inactivated by 2,3-butanedione, an arginyl-modifying reagent. The reaction followed pseudo-first-order kinetics and the modification was found to be reversible. Woodward's reagent K, a reagent for carboxyl residues, partially inactivated the enzyme, which resulted in a change of the NAD glycohydrolase kinetic parameters Km and V. The inactivation rate was complicated by a parallel decomposition of the reagent."}
{"id": "PMID:203461", "title": "Adenosine-3':5'-monophosphate-binding proteins from bovine kidney. Isolation by affinity chromatography and limited proteolysis of the regulatory subunit of protein kinase II.", "content": "Affinity chromatography on cyclic AMP columns allowed a two-step isolation of the cyclic-AMP-binding proteins from bovine kidney cytosol. An AMP-binding protein (apparent molecular weight approximately 60 000) and large amounts of a low affinity binding protein ('P35'; apparent subunit size approximately 35 000) were obtained in practically pure form besides the high affinity binding proteins of the R type. Among the R proteins the dimer R2 of the regulatory subunit of protein kinase II (apparent subunit size approximately 54 000) represented the bulk material. Small amounts of monomer, of higher aggregates, and of a protein 'P49' (subunit size approximately 49 000) presumably identical with the regulatory subunit of protein kinase I were also detected. The R protein fraction of kidney also contained a high affinity binding protein of smaller size (designated as R'; molecular weight approximately 37 000) which appeared to be derived from protein R2 of protein kinase II by limited proteolysis. At all stages of purification, R protein and its aggregates could be quantitatively transformed into R' protein (or a closely related polypeptide) by several proteases including the relatively unspecific proteinase K. The degradation product exhibited unchanged cyclic-AMP-binding capacities but had largely lost the ability to inhibit the catalytic subunit C of protein kinase, to be phosphorylated by C, and to form a dimer. Preliminary experiments indicate that protein R' may be a natural component of kidney tissue.", "contents": "Adenosine-3':5'-monophosphate-binding proteins from bovine kidney. Isolation by affinity chromatography and limited proteolysis of the regulatory subunit of protein kinase II. Affinity chromatography on cyclic AMP columns allowed a two-step isolation of the cyclic-AMP-binding proteins from bovine kidney cytosol. An AMP-binding protein (apparent molecular weight approximately 60 000) and large amounts of a low affinity binding protein ('P35'; apparent subunit size approximately 35 000) were obtained in practically pure form besides the high affinity binding proteins of the R type. Among the R proteins the dimer R2 of the regulatory subunit of protein kinase II (apparent subunit size approximately 54 000) represented the bulk material. Small amounts of monomer, of higher aggregates, and of a protein 'P49' (subunit size approximately 49 000) presumably identical with the regulatory subunit of protein kinase I were also detected. The R protein fraction of kidney also contained a high affinity binding protein of smaller size (designated as R'; molecular weight approximately 37 000) which appeared to be derived from protein R2 of protein kinase II by limited proteolysis. At all stages of purification, R protein and its aggregates could be quantitatively transformed into R' protein (or a closely related polypeptide) by several proteases including the relatively unspecific proteinase K. The degradation product exhibited unchanged cyclic-AMP-binding capacities but had largely lost the ability to inhibit the catalytic subunit C of protein kinase, to be phosphorylated by C, and to form a dimer. Preliminary experiments indicate that protein R' may be a natural component of kidney tissue."}
{"id": "PMID:203462", "title": "Structural homology of cytochromes c.", "content": "Cytochromes c from many eukaryotic and diverse prokaryotic organisms have been investigated and compared using high-resolution nuclear magnetic resonance spectroscopy. Resonances have been assigned to a large number of specific groups, mostly in the immediate environment of the heme. This information, together with sequence data, has allowed a comparison of the heme environment and protein conformation for these cytochromes. All mitochondrial cytochromes c are found to be very similar to the cytochromes c2 from Rhodospirillaceae. In the smaller bacterial cytochromes, Pseudomonas aeruginosa cytochrome c551 and Euglena gracilis cytochrome c552, the orientation of groups near the heme is very similar, but the folding of the polypeptide chain is different. The heme environment of these two proteins is similar to that of the larger bacterial and mitochondrial cytochromes. Two low-potential cytochromes, Desulfovibrio vulgaris cytochrome c553 and cytochrome c554 from a halotolerant micrococcus have heme environments which are not very similar to those of the other proteins reported here.", "contents": "Structural homology of cytochromes c. Cytochromes c from many eukaryotic and diverse prokaryotic organisms have been investigated and compared using high-resolution nuclear magnetic resonance spectroscopy. Resonances have been assigned to a large number of specific groups, mostly in the immediate environment of the heme. This information, together with sequence data, has allowed a comparison of the heme environment and protein conformation for these cytochromes. All mitochondrial cytochromes c are found to be very similar to the cytochromes c2 from Rhodospirillaceae. In the smaller bacterial cytochromes, Pseudomonas aeruginosa cytochrome c551 and Euglena gracilis cytochrome c552, the orientation of groups near the heme is very similar, but the folding of the polypeptide chain is different. The heme environment of these two proteins is similar to that of the larger bacterial and mitochondrial cytochromes. Two low-potential cytochromes, Desulfovibrio vulgaris cytochrome c553 and cytochrome c554 from a halotolerant micrococcus have heme environments which are not very similar to those of the other proteins reported here."}
{"id": "PMID:203464", "title": "Congenital generalized lipodystrophy with insulin-resistant diabetes.", "content": "Hyperglycemia, glucose intolerance, hyperinsulinemia and resistance to exogenous insulin were found in a 10-year-old Japanese boy diagnosed as having congenital generalized lipodystrophy. Studies on insulin receptors of circulating mononuclear leucocytes indicated that insulin-resistant diabetes combined with congenital generalized lipodystrophy may be due to disturbance of insulin binding to membrane receptors. No insulin-binding antibody or antibody that impairs insulin-receptor binding was found. Plasma glucagon showed an exaggerated response to L-arginine before treatment. After treatment with a controlled diet and an oral sulfonylurea (500 mg/day) for 4 weeks, there was improvement in the plasma glucagon response to L-arginine. Improvement in the hyperglycemia, hyperinsulinemia and acanthosis nigricans was also observed. On the other hand, on completion of a 7-day high-fat diet, a marked increase in serum free fatty acids, triglycerides and beta-lipoproteins was observed. The total plasma post-heparin lipolytic activity during the high fat diet was within the normal range. However, the level of protamine-inactivated activity was 3 times that of the control.", "contents": "Congenital generalized lipodystrophy with insulin-resistant diabetes. Hyperglycemia, glucose intolerance, hyperinsulinemia and resistance to exogenous insulin were found in a 10-year-old Japanese boy diagnosed as having congenital generalized lipodystrophy. Studies on insulin receptors of circulating mononuclear leucocytes indicated that insulin-resistant diabetes combined with congenital generalized lipodystrophy may be due to disturbance of insulin binding to membrane receptors. No insulin-binding antibody or antibody that impairs insulin-receptor binding was found. Plasma glucagon showed an exaggerated response to L-arginine before treatment. After treatment with a controlled diet and an oral sulfonylurea (500 mg/day) for 4 weeks, there was improvement in the plasma glucagon response to L-arginine. Improvement in the hyperglycemia, hyperinsulinemia and acanthosis nigricans was also observed. On the other hand, on completion of a 7-day high-fat diet, a marked increase in serum free fatty acids, triglycerides and beta-lipoproteins was observed. The total plasma post-heparin lipolytic activity during the high fat diet was within the normal range. However, the level of protamine-inactivated activity was 3 times that of the control."}
{"id": "PMID:203466", "title": "Congenital lactic acidosis due to pyruvate carboxylase deficiency: absence of an inhibitor of TPP-ATP phosphoryl transferase.", "content": "Two children are described who suffered from episodes of metabolic acidosis and progressive mental and motor deterioration. The patients showed periodic elevation of blood lactate, pyruvate and alanine, which was accompanied by vomiting, hypotonia or convulsions. The concentrations of lactate and pyruvate in cerebrospinal fluid were found to be increased. Liver biopsies revealed a decrease in pyruvate carboxylase activity and normal pyruvate decarboxylase activity. No inhibitor of TPP-ATP phosphoryl transferase was detected in urine from the patients. These findings suggest that congenital lactic acidosis due to pyruvate carboxylase deficiency is probably a different disease entity from Leigh's encephalomyelopathy. A possible mechanism of brain damage caused by a defect in pyruvate carboxylase is postulated.", "contents": "Congenital lactic acidosis due to pyruvate carboxylase deficiency: absence of an inhibitor of TPP-ATP phosphoryl transferase. Two children are described who suffered from episodes of metabolic acidosis and progressive mental and motor deterioration. The patients showed periodic elevation of blood lactate, pyruvate and alanine, which was accompanied by vomiting, hypotonia or convulsions. The concentrations of lactate and pyruvate in cerebrospinal fluid were found to be increased. Liver biopsies revealed a decrease in pyruvate carboxylase activity and normal pyruvate decarboxylase activity. No inhibitor of TPP-ATP phosphoryl transferase was detected in urine from the patients. These findings suggest that congenital lactic acidosis due to pyruvate carboxylase deficiency is probably a different disease entity from Leigh's encephalomyelopathy. A possible mechanism of brain damage caused by a defect in pyruvate carboxylase is postulated."}
{"id": "PMID:203468", "title": "Recurrent multiple cranial neuropathies.", "content": "A report of 12 patients with recurrent multiple cranial neuropathy is presented. In most cases the palsies a accompanied a mild respiratory infection. Both motor and sensory cranial nerves were affected, the facial nerve and optic nerve being the most common. The symptoms were self-limited in course and steroid therapy seemed to hasten the recovery in the cases it was used. Only in a few cases a noticeable neurological deficiency remained. Aetiological aspects of the syndrome are discussed.", "contents": "Recurrent multiple cranial neuropathies. A report of 12 patients with recurrent multiple cranial neuropathy is presented. In most cases the palsies a accompanied a mild respiratory infection. Both motor and sensory cranial nerves were affected, the facial nerve and optic nerve being the most common. The symptoms were self-limited in course and steroid therapy seemed to hasten the recovery in the cases it was used. Only in a few cases a noticeable neurological deficiency remained. Aetiological aspects of the syndrome are discussed."}
{"id": "PMID:203469", "title": "Use of trypsin for isolation of islets of Langerhans in the rat.", "content": "A new technique for pancreatic islet isolation, based on trypsin administered into the pancreatic duct system and a reduced amount of collagenase for digestion of the removed and chopped pancreatic tissue, yielded viable islets as judged by the metabolic response of 27 inbred, streptozotocin-diabetic rats after intraportal transplantation of the islets: all recipients of greater than 240 islets normalized their blood glucose, plasma insulin, urine volume and urinary glucose. The number of islets isolated was the same as with the conventional collagenase technique.", "contents": "Use of trypsin for isolation of islets of Langerhans in the rat. A new technique for pancreatic islet isolation, based on trypsin administered into the pancreatic duct system and a reduced amount of collagenase for digestion of the removed and chopped pancreatic tissue, yielded viable islets as judged by the metabolic response of 27 inbred, streptozotocin-diabetic rats after intraportal transplantation of the islets: all recipients of greater than 240 islets normalized their blood glucose, plasma insulin, urine volume and urinary glucose. The number of islets isolated was the same as with the conventional collagenase technique."}
{"id": "PMID:203472", "title": "Modification of theophylline-induced lipolysis in human fat cells after trypsination.", "content": "Trypsin-treatment of human fat cells results in the potentiation of the lipolytic response and the cAMP accumulation induced by theophylline (5 . 10(-4) M) but not of those induced by theophylline (5 . 10(-3) M). The amount of cAMP formed after exposure to theophylline (5 . 10(-3) M) plus norepinephrine (5 . 10(-6) M) remains, however, 2.6 fold higher in trypsin-treated human fat cells than in the control ones.", "contents": "Modification of theophylline-induced lipolysis in human fat cells after trypsination. Trypsin-treatment of human fat cells results in the potentiation of the lipolytic response and the cAMP accumulation induced by theophylline (5 . 10(-4) M) but not of those induced by theophylline (5 . 10(-3) M). The amount of cAMP formed after exposure to theophylline (5 . 10(-3) M) plus norepinephrine (5 . 10(-6) M) remains, however, 2.6 fold higher in trypsin-treated human fat cells than in the control ones."}
{"id": "PMID:203473", "title": "Search for sex-dependent and gestation-induced changes in choline and ethanolamine phosphorylating activities.", "content": "Choline kinase and ethanolamine kinase of liver, brain and kidney had nearly the same activity in 4-month-old male and virgin female mice. Ethanolamine kinase activity was almost doubled in the liver and brain of mice in advanced pregnancy compared with the virgin, while choline kinase activity was unaltered.", "contents": "Search for sex-dependent and gestation-induced changes in choline and ethanolamine phosphorylating activities. Choline kinase and ethanolamine kinase of liver, brain and kidney had nearly the same activity in 4-month-old male and virgin female mice. Ethanolamine kinase activity was almost doubled in the liver and brain of mice in advanced pregnancy compared with the virgin, while choline kinase activity was unaltered."}
{"id": "PMID:203474", "title": "Effect of low density lipoprotein on proteoglycan synthesis by aorta cells in culture.", "content": "Increasing the content of human serum low density lipoprotein in the growth medium led to greater incorporation of 35S-sulfate into proteoglycan (mostly into dermatan sulfate) by primary aorta cells but did not affect similar incorporation by fibroblast cells. These results suggest a mechanism which can explain the increased deposition of lipid in aorta due to hyperlipidemia.", "contents": "Effect of low density lipoprotein on proteoglycan synthesis by aorta cells in culture. Increasing the content of human serum low density lipoprotein in the growth medium led to greater incorporation of 35S-sulfate into proteoglycan (mostly into dermatan sulfate) by primary aorta cells but did not affect similar incorporation by fibroblast cells. These results suggest a mechanism which can explain the increased deposition of lipid in aorta due to hyperlipidemia."}
{"id": "PMID:203475", "title": "The metabolism of methadone by cultured mammalian cells.", "content": "Rat hepatoma tissue culture cells and mouse leukemic cells were found to metabolize [1-3H] methadone to at least 2 unidentified radioactive compounds. These results suggest that cultured cells may be useful models for studying methadone metabolism by specific cell types.", "contents": "The metabolism of methadone by cultured mammalian cells. Rat hepatoma tissue culture cells and mouse leukemic cells were found to metabolize [1-3H] methadone to at least 2 unidentified radioactive compounds. These results suggest that cultured cells may be useful models for studying methadone metabolism by specific cell types."}
{"id": "PMID:203476", "title": "Effect of sodium octanoate on leucine incorporation into protein of rat liver slices and of Yoshida ascites hepatoma cells.", "content": "7.38 X 10(-4) M octanoate does not significantly modify leucine incorporation into protein of rat liver slices, while in hepatoma cells a 19% inhibition has been noted. 3.69 x 10(-3) M octanoate reduces leucine incorporation to about the same extent (71-76%) in both liver slices and hepatoma cells.", "contents": "Effect of sodium octanoate on leucine incorporation into protein of rat liver slices and of Yoshida ascites hepatoma cells. 7.38 X 10(-4) M octanoate does not significantly modify leucine incorporation into protein of rat liver slices, while in hepatoma cells a 19% inhibition has been noted. 3.69 x 10(-3) M octanoate reduces leucine incorporation to about the same extent (71-76%) in both liver slices and hepatoma cells."}
{"id": "PMID:203477", "title": "Evidence for possible emergence of immunochemically distinct nucleotide-peptides in malignant transformation.", "content": "Antibodies against nucleotide-peptides of beef heart do crossreact with nucleotide-peptides of other beef organs, but with nucleotide-peptides of Ehrlich tumor cells. Antibodies against the latter do not crossreact with nucleotide-peptides of normal organs, but do so with nucleotide-peptides of a rat hepatoma.", "contents": "Evidence for possible emergence of immunochemically distinct nucleotide-peptides in malignant transformation. Antibodies against nucleotide-peptides of beef heart do crossreact with nucleotide-peptides of other beef organs, but with nucleotide-peptides of Ehrlich tumor cells. Antibodies against the latter do not crossreact with nucleotide-peptides of normal organs, but do so with nucleotide-peptides of a rat hepatoma."}
{"id": "PMID:203480", "title": "[Effect of prostaglandin F2alpha on inhibitory and excitative processes in the sensory nerve endings of the cornea].", "content": "In concentration of 0.002 to 0.025 per cent prostaglandin F2alpha potentiated the anesthetic action of dicain and decreased the mitigating effect of acetylcholine in regard to dicain-induced anesthesia. These facts prove that prostaglandin F2alpha can in certain conditions attenuate the process of excitation and intensity that of inhibition in the sensory endings of the cornea.", "contents": "[Effect of prostaglandin F2alpha on inhibitory and excitative processes in the sensory nerve endings of the cornea]. In concentration of 0.002 to 0.025 per cent prostaglandin F2alpha potentiated the anesthetic action of dicain and decreased the mitigating effect of acetylcholine in regard to dicain-induced anesthesia. These facts prove that prostaglandin F2alpha can in certain conditions attenuate the process of excitation and intensity that of inhibition in the sensory endings of the cornea."}
{"id": "PMID:203489", "title": "Identification and regulation of alpha- and beta-adrenergic receptors.", "content": "Direct radioligand binding methods for studying the alpha- and beta-adrenergic receptors have been developed over the past several years. These techniques use radioactively labeled adrenergic antagonists and agonists to identify the receptors in appropriate membrane fractions from catecholamine-sensitive tissues. In the case of the beta-adrenergic receptors, confident receptor identification has been aided by the close correlation of binding data with data on adenylate cyclase activation. Such direct binding studies are providing new insights about the molecular characteristics and regulatory properties of the receptors.", "contents": "Identification and regulation of alpha- and beta-adrenergic receptors. Direct radioligand binding methods for studying the alpha- and beta-adrenergic receptors have been developed over the past several years. These techniques use radioactively labeled adrenergic antagonists and agonists to identify the receptors in appropriate membrane fractions from catecholamine-sensitive tissues. In the case of the beta-adrenergic receptors, confident receptor identification has been aided by the close correlation of binding data with data on adenylate cyclase activation. Such direct binding studies are providing new insights about the molecular characteristics and regulatory properties of the receptors."}
{"id": "PMID:203492", "title": "Possible involvement of cerebroside sulfate in opiate receptor binding.", "content": "Cerebroside sulfate (CS) appears to fulfill most of the structural requirements of a hypothetical opiate receptor. It possesses many of the properties that are thought to be necessary for the identification of an \"opiate receptor,\" exhibiting high affinity and stereoselective binding to a number of narcotic drugs. Although these properties are insufficient to establish identity of the receptor, it is highly significant that the affinity of this binding can be correlated with the analgetic potency of these drugs in both man and rodents. CS is an endogenous component of brain tissue, and a partially purified opiate receptor from mouse brain has been found to be CS. Other experiments indicate that reduced availability of brain CS decreases the analgetic effects of morphine and this is accompanied by a reduction in number of binding sites, suggesting that the interaction of opiates with CS observed in vitro may also have importance in vivo. CS was also found to be a component of the opiate receptor after marking with 125I-labeled diazosulfanilic acid. The possibility that CS or the SO4-2 group of this lipid may be the \"anionic site\" of the opiate receptor should be considered.", "contents": "Possible involvement of cerebroside sulfate in opiate receptor binding. Cerebroside sulfate (CS) appears to fulfill most of the structural requirements of a hypothetical opiate receptor. It possesses many of the properties that are thought to be necessary for the identification of an \"opiate receptor,\" exhibiting high affinity and stereoselective binding to a number of narcotic drugs. Although these properties are insufficient to establish identity of the receptor, it is highly significant that the affinity of this binding can be correlated with the analgetic potency of these drugs in both man and rodents. CS is an endogenous component of brain tissue, and a partially purified opiate receptor from mouse brain has been found to be CS. Other experiments indicate that reduced availability of brain CS decreases the analgetic effects of morphine and this is accompanied by a reduction in number of binding sites, suggesting that the interaction of opiates with CS observed in vitro may also have importance in vivo. CS was also found to be a component of the opiate receptor after marking with 125I-labeled diazosulfanilic acid. The possibility that CS or the SO4-2 group of this lipid may be the \"anionic site\" of the opiate receptor should be considered."}
{"id": "PMID:203493", "title": "Histochemical localization of opiate receptors and opioid peptides.", "content": "It is possible to localize opiate receptors by histochemical methods. They appear in high densities in anatomical areas associated with physiologic functions altered by opiates. They appear to mediate inhibitory responses; some of them, in certain regions could be involved in axo-axonic synapses. The immunohistochemical studies as well as the electrophysiologic results are compatible with the view that the enkephalins are the endogenous substrates for the opiate receptors.", "contents": "Histochemical localization of opiate receptors and opioid peptides. It is possible to localize opiate receptors by histochemical methods. They appear in high densities in anatomical areas associated with physiologic functions altered by opiates. They appear to mediate inhibitory responses; some of them, in certain regions could be involved in axo-axonic synapses. The immunohistochemical studies as well as the electrophysiologic results are compatible with the view that the enkephalins are the endogenous substrates for the opiate receptors."}
{"id": "PMID:203495", "title": "Leydig and Sertoli cell function in normal and oligospermic males: a preliminary report.", "content": "Sertoli and Leydig cell function was evaluated in patients with oligospermia. Testicular biopsy specimens were incubated in vitro with follicle-stimulating hormone (FSH) or luteinizing  hormone (LH), and the amount of cyclic adenosine 3':5'-monophosphate (cyclic AMP) generated was measured. Cyclic AMP has been shown to be intracellular mediator for the pituitary gonadotropins FSH and LH. The amount generated by the Sertoli cells response to FSH, and by the Leydig cells in response to LH, was contrasted with that in age-matched, normal control subjects. The Leydig cell response was similar in both groups. However, the amount of cyclic AMP generated by the Sertoli cells from oligospermic males was much less when compared with normal control subjects. This finding suggests a possible metabolic abnormality in the Sertoli cells of patients with oligospermia which might, in turn, alter spermatogenesis.", "contents": "Leydig and Sertoli cell function in normal and oligospermic males: a preliminary report. Sertoli and Leydig cell function was evaluated in patients with oligospermia. Testicular biopsy specimens were incubated in vitro with follicle-stimulating hormone (FSH) or luteinizing  hormone (LH), and the amount of cyclic adenosine 3':5'-monophosphate (cyclic AMP) generated was measured. Cyclic AMP has been shown to be intracellular mediator for the pituitary gonadotropins FSH and LH. The amount generated by the Sertoli cells response to FSH, and by the Leydig cells in response to LH, was contrasted with that in age-matched, normal control subjects. The Leydig cell response was similar in both groups. However, the amount of cyclic AMP generated by the Sertoli cells from oligospermic males was much less when compared with normal control subjects. This finding suggests a possible metabolic abnormality in the Sertoli cells of patients with oligospermia which might, in turn, alter spermatogenesis."}
{"id": "PMID:203498", "title": "The association between oral contraception and hepatocellular adenoma--a preliminary report.", "content": "Women with long-term use of oral contraception (OC) are at increased risk of developing a serious, though nonmalignant, liver tumor--hepatocellular ademona (HCA)--according to a case-control study conducted by the Center for Disease Control (CDC) in collaboration with the Armed Forces Institute of Pathology (AFIP). The tumor is sometimes fatal, deaths usually being due to sudden rupture and hemorrhage. This study suggests that, in addition to long-term OC use, a women's age and the hormonal potency of the OC she uses affect her changes of developing HCA. Women 27 years old and older who have used OC with high hormonal potency for 7 or more years are at the greatest risk.", "contents": "The association between oral contraception and hepatocellular adenoma--a preliminary report. Women with long-term use of oral contraception (OC) are at increased risk of developing a serious, though nonmalignant, liver tumor--hepatocellular ademona (HCA)--according to a case-control study conducted by the Center for Disease Control (CDC) in collaboration with the Armed Forces Institute of Pathology (AFIP). The tumor is sometimes fatal, deaths usually being due to sudden rupture and hemorrhage. This study suggests that, in addition to long-term OC use, a women's age and the hormonal potency of the OC she uses affect her changes of developing HCA. Women 27 years old and older who have used OC with high hormonal potency for 7 or more years are at the greatest risk."}
{"id": "PMID:203500", "title": "Steroidogenesis in isolated adrenal cells: excitation by calcium.", "content": "Calcium salts were found to replace ACTH in inducing steroidogenesis in isolated adrenocortical cells from rats. This Ca-specific stimulation occurred when the cation was presented to the cells in the presence of phosphate and carbonate as a counter-ions under conditions which favoured the formation of colloidal calcium. Colloid generation and stabilization was facilitated by the use of calcium buffers and gelatin. Stable soluble or sparingly soluble calcium complexes were inactive. The preparation of cells and metastable calcium solutions is described in detail. The Ca trigger was sensitive to Ca deprivation or inhibitors of Ca transport and could be replced by Sr. The relative role of Ca and cyclic AMP as second messengers is discussed.", "contents": "Steroidogenesis in isolated adrenal cells: excitation by calcium. Calcium salts were found to replace ACTH in inducing steroidogenesis in isolated adrenocortical cells from rats. This Ca-specific stimulation occurred when the cation was presented to the cells in the presence of phosphate and carbonate as a counter-ions under conditions which favoured the formation of colloidal calcium. Colloid generation and stabilization was facilitated by the use of calcium buffers and gelatin. Stable soluble or sparingly soluble calcium complexes were inactive. The preparation of cells and metastable calcium solutions is described in detail. The Ca trigger was sensitive to Ca deprivation or inhibitors of Ca transport and could be replced by Sr. The relative role of Ca and cyclic AMP as second messengers is discussed."}
{"id": "PMID:203501", "title": "Effect of cordycepin on CRF stimulation and steroid inhibition of ACTH secretion by rat pituitary cells.", "content": "Isolated pituitary cells prepared from adrenalectomized rats secrete ACTH in response to CRF, and this response is inhibited by corticosterone. Both the stimulation of release by CRF and the inhibition of release by corticosterone are antagonized by cordycepin (3'-deoxyadenosine). Inhibition of CRF-stimulated secretion by cordycepin is apparently not related to inhibition of RNA synthesis, since high doses of actinomycin D do not affect ACTH secretion. More likely, cordycepin's inhibition of secretion stems from its inhibition of adenylate cyclase activity. Inhibition of corticosterone action by cordycepin is qualitatively similar to that previously reported actinomycin D. This effect of both drugs is probably due to inhibition of RNA synthesis. Significantly, a low dose of cordycepin has a greater inhibitory effect on corticosterone action than on total cellular RNA synthesis. Cordycepin is reported to preferentially inhibit messenger RNA synthesis, and low dose preferentially inhibits appearance of cytoplasmic RNA in pituitary cells. These data suggest that corticosterone-induced RNA is a cytoplasmic (messenger) RNA.", "contents": "Effect of cordycepin on CRF stimulation and steroid inhibition of ACTH secretion by rat pituitary cells. Isolated pituitary cells prepared from adrenalectomized rats secrete ACTH in response to CRF, and this response is inhibited by corticosterone. Both the stimulation of release by CRF and the inhibition of release by corticosterone are antagonized by cordycepin (3'-deoxyadenosine). Inhibition of CRF-stimulated secretion by cordycepin is apparently not related to inhibition of RNA synthesis, since high doses of actinomycin D do not affect ACTH secretion. More likely, cordycepin's inhibition of secretion stems from its inhibition of adenylate cyclase activity. Inhibition of corticosterone action by cordycepin is qualitatively similar to that previously reported actinomycin D. This effect of both drugs is probably due to inhibition of RNA synthesis. Significantly, a low dose of cordycepin has a greater inhibitory effect on corticosterone action than on total cellular RNA synthesis. Cordycepin is reported to preferentially inhibit messenger RNA synthesis, and low dose preferentially inhibits appearance of cytoplasmic RNA in pituitary cells. These data suggest that corticosterone-induced RNA is a cytoplasmic (messenger) RNA."}
{"id": "PMID:203502", "title": "Thyrotropin receptors in adipose tissue, retro-orbital tissue and lymphocytes.", "content": "Thyrotropin (TSH) receptors on retro-orbital muscle and fat have been implicated in the pathogenesis of Graves' exophthalmos and it has been suggested that TSH has a direct effect on human fat metabolism. We have therefore investigated the interaction of biologically active 125I-labelled TSH with membranes prepared from human adipose, retro-orbital and thyroid tissue. Since lymphocytes contain receptors for several polypeptide hormones, TSH binding to lymphocyte membranes was also studied. We were unable to demonstrate TSH receptors in adult human adipose tissue, retro-orbital muscle and fat, or peripheral blood lymphocytes. In contrast, adult and neonatal guinea pig adipose tissue membranes showed similar TSH binding characteristics to guinea pig thyroid membranes.", "contents": "Thyrotropin receptors in adipose tissue, retro-orbital tissue and lymphocytes. Thyrotropin (TSH) receptors on retro-orbital muscle and fat have been implicated in the pathogenesis of Graves' exophthalmos and it has been suggested that TSH has a direct effect on human fat metabolism. We have therefore investigated the interaction of biologically active 125I-labelled TSH with membranes prepared from human adipose, retro-orbital and thyroid tissue. Since lymphocytes contain receptors for several polypeptide hormones, TSH binding to lymphocyte membranes was also studied. We were unable to demonstrate TSH receptors in adult human adipose tissue, retro-orbital muscle and fat, or peripheral blood lymphocytes. In contrast, adult and neonatal guinea pig adipose tissue membranes showed similar TSH binding characteristics to guinea pig thyroid membranes."}
{"id": "PMID:203503", "title": "Selected properties of [3H]prostaglandin E1 binding to dispersed bovine luteal cells.", "content": "Selected properties of [3H]prostaglandin (PG) E1 binding to collagenase dispersed bovine luteal cells were studied and compared with those observed in luteal plasma membranes. [3H]-PGE1 specific binding to a relatively homogeneous population of luteal cells was a rapid (K1 = 4.2 X 10(5) M-1 .sec-1), reversible (K-1 = 3.9 X 10(-3) sec-1), saturable and specific process at 38 degrees C. The binding was homogeneous with an apparent dissociation constant of 2.4 nM and 1.8 X 10(5) receptors per cell. The presence of increasing amounts of unlabeled PGs inhibited [3H]PGE1 binding in a dose-dependent manner. The potency order for this inhibition of binding was: PGE 2 greater than PGE1, (15S)-15-methyl-PGE2 methyl ester greater than PGF2alpha greater than PGF1alpha greater than other PGs, PGE, PGF metabolites and PGF analogs. Other than the homogeneous nature of [3H]PGE1 binding and the greater effectiveness of PGE2 compared to PGE1 in cells, the rest of the properties of [3H]PGE1 binding to cells were in excellent agreement with those observed in plasma membranes.", "contents": "Selected properties of [3H]prostaglandin E1 binding to dispersed bovine luteal cells. Selected properties of [3H]prostaglandin (PG) E1 binding to collagenase dispersed bovine luteal cells were studied and compared with those observed in luteal plasma membranes. [3H]-PGE1 specific binding to a relatively homogeneous population of luteal cells was a rapid (K1 = 4.2 X 10(5) M-1 .sec-1), reversible (K-1 = 3.9 X 10(-3) sec-1), saturable and specific process at 38 degrees C. The binding was homogeneous with an apparent dissociation constant of 2.4 nM and 1.8 X 10(5) receptors per cell. The presence of increasing amounts of unlabeled PGs inhibited [3H]PGE1 binding in a dose-dependent manner. The potency order for this inhibition of binding was: PGE 2 greater than PGE1, (15S)-15-methyl-PGE2 methyl ester greater than PGF2alpha greater than PGF1alpha greater than other PGs, PGE, PGF metabolites and PGF analogs. Other than the homogeneous nature of [3H]PGE1 binding and the greater effectiveness of PGE2 compared to PGE1 in cells, the rest of the properties of [3H]PGE1 binding to cells were in excellent agreement with those observed in plasma membranes."}
{"id": "PMID:203504", "title": "Properties of solubilized nuclear triiodothyronine binding proteins.", "content": "Rat liver nuclear proteins bind 3,5,3'-triiodo-L-thyronine (T3) to essentially one class of sites (Ka approximately 1 X 10(10) M-1). Gel filtration and sucrose gradient centrifugation studies show a main T3 binding component with a Stokes radius of 33 A and a sedimentation coefficient of 3.5S, and variable amounts of high molecular weight binding components, most of them being reversible aggregates of the main component formed during storage. But the uniqueness of the nuclean T3 binding proteins (NTBP) cannot be ascertained from polyacrylamide gel electrophoresis data. During storage in the absence of reducing agents, NTBP aggregate and rapidly lose their ability to bind T3; T3--NTBP complexes also aggregate and progressively dissociate. This can be reversed by dithiothreitol. Bound T3 could temporarily stabilize the binding site but cannot protect NTBP against general conformational changes which follow the oxidation of their essential --SH group(s). NTBP are DNA binding proteins with probably a relative independence of their DNA and T3 binding sites: they bind T3 to the same class of high affinity sites whether complexed or not with DNA; bound T3 is not a prerequisite for DNA binding.", "contents": "Properties of solubilized nuclear triiodothyronine binding proteins. Rat liver nuclear proteins bind 3,5,3'-triiodo-L-thyronine (T3) to essentially one class of sites (Ka approximately 1 X 10(10) M-1). Gel filtration and sucrose gradient centrifugation studies show a main T3 binding component with a Stokes radius of 33 A and a sedimentation coefficient of 3.5S, and variable amounts of high molecular weight binding components, most of them being reversible aggregates of the main component formed during storage. But the uniqueness of the nuclean T3 binding proteins (NTBP) cannot be ascertained from polyacrylamide gel electrophoresis data. During storage in the absence of reducing agents, NTBP aggregate and rapidly lose their ability to bind T3; T3--NTBP complexes also aggregate and progressively dissociate. This can be reversed by dithiothreitol. Bound T3 could temporarily stabilize the binding site but cannot protect NTBP against general conformational changes which follow the oxidation of their essential --SH group(s). NTBP are DNA binding proteins with probably a relative independence of their DNA and T3 binding sites: they bind T3 to the same class of high affinity sites whether complexed or not with DNA; bound T3 is not a prerequisite for DNA binding."}
{"id": "PMID:203506", "title": "Regional pancreatic concentration and in-vitro secretion of canine pancreatic polypeptide, insulin, and glucagon.", "content": "The regional concentrations and in-vitro secretions of canine pancreatic polypeptide (cPP), insulin, and glucagon were studied. CPP is found predominantly in the uncinate process of the dog pancreas, whereas insulin and, more markedly, glucagon predominate in the body and tail of the pancreas. In-vitro secretion studies of pancreatic pieces indicate that dibutyryl cyclic AMP (dcAMP) alone can stimulate cPP release whereas glucose and arginine alone have no effect. Arginine, but not glucose, potentiates this stimulant effect of dcAMP. These studies suggest that the cAMP generating system may play a role in regulation of cPP secretion.", "contents": "Regional pancreatic concentration and in-vitro secretion of canine pancreatic polypeptide, insulin, and glucagon. The regional concentrations and in-vitro secretions of canine pancreatic polypeptide (cPP), insulin, and glucagon were studied. CPP is found predominantly in the uncinate process of the dog pancreas, whereas insulin and, more markedly, glucagon predominate in the body and tail of the pancreas. In-vitro secretion studies of pancreatic pieces indicate that dibutyryl cyclic AMP (dcAMP) alone can stimulate cPP release whereas glucose and arginine alone have no effect. Arginine, but not glucose, potentiates this stimulant effect of dcAMP. These studies suggest that the cAMP generating system may play a role in regulation of cPP secretion."}
{"id": "PMID:203507", "title": "Idiopathic granulomatous hepatitis with a prolonged course: effect of corticosteroid therapy.", "content": "The effect of corticosteroid (or ACTH) therapy on 4 patients with idiopathic granulomatous hepatitis is described. All patients presented with spiking fever and chills and none had jaundice. Only 1 patient had an enlarged tender liver and 3 had splenomegaly. The erythrocyte sedimentation rate was increased in all cases while the white blood cell count was typically normal. Impairment in liver function was insignificant and consisted of a mild elevation of SGOT and alkaline phosphatase activities and prolonged prothrombin time. All patients presented a diagnostic challenge. The diagnosis was established by routine liver biopsies in 3 cases and by laparotomy in the 4th. The etiology could not be established. All patients reacted dramatically to prednisone (or ACTH) after failure of other therapeutic regimens. The disease has, however, been present for 5 years in 1 patient and 10 years in another, Relapses occur after cessation of therapy.", "contents": "Idiopathic granulomatous hepatitis with a prolonged course: effect of corticosteroid therapy. The effect of corticosteroid (or ACTH) therapy on 4 patients with idiopathic granulomatous hepatitis is described. All patients presented with spiking fever and chills and none had jaundice. Only 1 patient had an enlarged tender liver and 3 had splenomegaly. The erythrocyte sedimentation rate was increased in all cases while the white blood cell count was typically normal. Impairment in liver function was insignificant and consisted of a mild elevation of SGOT and alkaline phosphatase activities and prolonged prothrombin time. All patients presented a diagnostic challenge. The diagnosis was established by routine liver biopsies in 3 cases and by laparotomy in the 4th. The etiology could not be established. All patients reacted dramatically to prednisone (or ACTH) after failure of other therapeutic regimens. The disease has, however, been present for 5 years in 1 patient and 10 years in another, Relapses occur after cessation of therapy."}
{"id": "PMID:203508", "title": "The metabolic fate of high density lipoprotein (HDL) in the diabetic rat.", "content": "Diabetic rats, pre-fed and maintained on a sucrose-rich diet, have marked hyperlipoproteinaemia, with an increase in both very low density (VLDL) and high density lipoproteins (HDL). HDL obtained from both diabetic and non-diabetic rats and labelled with 125I or 135I was injected simultaneously into diabetic and non-diabetic rats. The half life of the two HDL preparations was similar in both diabetic and non-diabetic rats and ranged between 11.4 to 12.0 hours. A-I apolipoprotein had a disappearance rate parallel to the whole HDL, in contrast to the apo-C peptides which had a faster rate of removal. Although the fractional catabolic rate (FCR) of HDL preparations was slower in the diabetic rats, there was a 16% increase in the calculated synthetic rate (SR) of HDL-protein. These observations could explain the increased plasma HDL levels in the sucrose-fed, streptozotocin-induced diabetic rat.", "contents": "The metabolic fate of high density lipoprotein (HDL) in the diabetic rat. Diabetic rats, pre-fed and maintained on a sucrose-rich diet, have marked hyperlipoproteinaemia, with an increase in both very low density (VLDL) and high density lipoproteins (HDL). HDL obtained from both diabetic and non-diabetic rats and labelled with 125I or 135I was injected simultaneously into diabetic and non-diabetic rats. The half life of the two HDL preparations was similar in both diabetic and non-diabetic rats and ranged between 11.4 to 12.0 hours. A-I apolipoprotein had a disappearance rate parallel to the whole HDL, in contrast to the apo-C peptides which had a faster rate of removal. Although the fractional catabolic rate (FCR) of HDL preparations was slower in the diabetic rats, there was a 16% increase in the calculated synthetic rate (SR) of HDL-protein. These observations could explain the increased plasma HDL levels in the sucrose-fed, streptozotocin-induced diabetic rat."}
{"id": "PMID:203505", "title": "Cell mediated immunity in experimental influenza and parainfluenza infection.", "content": "Cell mediated immunity (CMI) to Sendai and Kunz viruses, determined by a 51Cr release assay of cytotoxicity, has been shown to develop during the course of these infections. This virus specific response is mediated by sensitised T cells, and takes place against a background of innate cell mediated immunity. The mediator of this innate cytotoxicity exhibits none of the characteristics of T, B or K cells, but bears close resemblance to the NK cell which is spontaneously cytotoxic for certain tumour cells. Removal of the virus specific CMI by T cell depletion produces a moderate immunosuppressive effect. The nature of this effect and the role of CMI in these infections are discussed.", "contents": "Cell mediated immunity in experimental influenza and parainfluenza infection. Cell mediated immunity (CMI) to Sendai and Kunz viruses, determined by a 51Cr release assay of cytotoxicity, has been shown to develop during the course of these infections. This virus specific response is mediated by sensitised T cells, and takes place against a background of innate cell mediated immunity. The mediator of this innate cytotoxicity exhibits none of the characteristics of T, B or K cells, but bears close resemblance to the NK cell which is spontaneously cytotoxic for certain tumour cells. Removal of the virus specific CMI by T cell depletion produces a moderate immunosuppressive effect. The nature of this effect and the role of CMI in these infections are discussed."}
{"id": "PMID:203511", "title": "[Effect of mutations for adenylate cyclase (cya) and the cyclic adenosine monophosphate receptor protein (cgp) on the gene expression of nucleoside catabolism in Escherichia coli].", "content": "The effect of cya and crp mutations on the expression of the activity of nucleoside catabolizing genes has been studied in Escherichia coli. It is found that cya and crp mutants lose their ability to grow on nucleosides as carbon sources in spite of the preservation of the basal levels of nucleoside catabolizing enzymes, found in cell-free extracts of cya and crp mutants. It is shown that cya and crp mutations completely release the influence of the regulatory gene cytR on the activity of uridine phosphorylase (udp gene) and thymidine phosphorylase (tpp gene). On this ground it is assumed that the cytR gene product acts at the level of promotors of the corresponding structural genes, causing their insensitivity to the positive action of cAMP--CRP complex. The same data concerning the effect of cya and crp mutations on cytR regulation have been reported [8], but these authors favoured the hypothesis that the cytR gene product is a repressor protein, which binds to the specific operator.", "contents": "[Effect of mutations for adenylate cyclase (cya) and the cyclic adenosine monophosphate receptor protein (cgp) on the gene expression of nucleoside catabolism in Escherichia coli]. The effect of cya and crp mutations on the expression of the activity of nucleoside catabolizing genes has been studied in Escherichia coli. It is found that cya and crp mutants lose their ability to grow on nucleosides as carbon sources in spite of the preservation of the basal levels of nucleoside catabolizing enzymes, found in cell-free extracts of cya and crp mutants. It is shown that cya and crp mutations completely release the influence of the regulatory gene cytR on the activity of uridine phosphorylase (udp gene) and thymidine phosphorylase (tpp gene). On this ground it is assumed that the cytR gene product acts at the level of promotors of the corresponding structural genes, causing their insensitivity to the positive action of cAMP--CRP complex. The same data concerning the effect of cya and crp mutations on cytR regulation have been reported [8], but these authors favoured the hypothesis that the cytR gene product is a repressor protein, which binds to the specific operator."}
{"id": "PMID:203514", "title": "Experimental infection of pheasants with Lednice (Yaba 1) virus.", "content": "Young pheasants (24-hour- and 7-day-old) are capable of producing viraemia and antibodies after experimental infection with Lednice virus even after low doses of virus (0.7-0.9 log mouse LD50/g). Viraemia lasts approximately 3 days, but the titres of virus in the blood are low. The possible role of young pheasants in the circulation of virus in nature is discussed.", "contents": "Experimental infection of pheasants with Lednice (Yaba 1) virus. Young pheasants (24-hour- and 7-day-old) are capable of producing viraemia and antibodies after experimental infection with Lednice virus even after low doses of virus (0.7-0.9 log mouse LD50/g). Viraemia lasts approximately 3 days, but the titres of virus in the blood are low. The possible role of young pheasants in the circulation of virus in nature is discussed."}
{"id": "PMID:203515", "title": "[A new topographic method for localising the venous angle of the deep cerebral veins on the lateral phlebographic phase (author's transl)].", "content": "A simple topographic method has been developed for the localisation of the venous angle on the lateral cerebral phlebogram. The principle depends on an angular measurement and an estimation of proportions which are statistically independant of each other. The method was tested on 103 phlebograms of adult patients with supratentorial spaceoccupying lesions. It was compared with conventional measurements; a number of advantages were found for using our method and its accuracy is as good as the other, most precise, methods.", "contents": "[A new topographic method for localising the venous angle of the deep cerebral veins on the lateral phlebographic phase (author's transl)]. A simple topographic method has been developed for the localisation of the venous angle on the lateral cerebral phlebogram. The principle depends on an angular measurement and an estimation of proportions which are statistically independant of each other. The method was tested on 103 phlebograms of adult patients with supratentorial spaceoccupying lesions. It was compared with conventional measurements; a number of advantages were found for using our method and its accuracy is as good as the other, most precise, methods."}
{"id": "PMID:203520", "title": "[Electroencephalography in clinical research into psychoses (author's transl)].", "content": "At present EEG investigations in heterogenous acute schizophrenic and psychotic syndromes suggest changes in the regulating, reticulo-thalamo-cortical, functional system. One may further assume that cerebral functional changes consist of a dissociation of normally closely linked functional systems. In favor are findings in functional psychoses (\"Funktionspsychosen\"), also the dissociation of usually coordinated systems in normal psychologic changes during going to sleep and REM stages of dreams. A further thalamohippocampo-reticulo system which might act in parallel to the activating reticular system has become important in EEG research into psychoses. Changes here probably in part of focal EEG phenomenon localized in the temporal region. Here, too, EEG findings in schizophrenic syndromes requiring further proof emerge.", "contents": "[Electroencephalography in clinical research into psychoses (author's transl)]. At present EEG investigations in heterogenous acute schizophrenic and psychotic syndromes suggest changes in the regulating, reticulo-thalamo-cortical, functional system. One may further assume that cerebral functional changes consist of a dissociation of normally closely linked functional systems. In favor are findings in functional psychoses (\"Funktionspsychosen\"), also the dissociation of usually coordinated systems in normal psychologic changes during going to sleep and REM stages of dreams. A further thalamohippocampo-reticulo system which might act in parallel to the activating reticular system has become important in EEG research into psychoses. Changes here probably in part of focal EEG phenomenon localized in the temporal region. Here, too, EEG findings in schizophrenic syndromes requiring further proof emerge."}
{"id": "PMID:203521", "title": "Carbon and hydrogen metabolism of xylitol and various sugars in human erythrocytes.", "content": "1) Erythrocytes are able to metabolize D-ribose, D-xylitol, D-xylulose, D-fructose and D-glucose; the rates of metabolism increase in that order from 2430 to 26200 ng atom C/ml packed cells per 120 min of incubation. 2) The utilization of the carbon of these substrates and its recovery in the products were found to be in balance, when the change in the 2,3-bisphosphoglycerate concentration was taken into account. 3) The metabolic rates strongly affected the 2,3-bisphosphoglycerate level. Without addition of substrate the decomposition rate of this intermediate was found to be 1030 nmol/ml packed cells per 120 min. 4) The net decrease of the 2,3-bisphosphoglycerate concentration and the conversion of this compound into lactate provides a NAD regeneration system which enables the red blood cells to utilize xylitol. 5) The rate of carbon metabolism via the pentose phosphate cycle is determined by the NADPH requirement of the erythrocytes which was found to be 160 nmol/ml packed cells per 120 min under the experimental conditions employed.", "contents": "Carbon and hydrogen metabolism of xylitol and various sugars in human erythrocytes. 1) Erythrocytes are able to metabolize D-ribose, D-xylitol, D-xylulose, D-fructose and D-glucose; the rates of metabolism increase in that order from 2430 to 26200 ng atom C/ml packed cells per 120 min of incubation. 2) The utilization of the carbon of these substrates and its recovery in the products were found to be in balance, when the change in the 2,3-bisphosphoglycerate concentration was taken into account. 3) The metabolic rates strongly affected the 2,3-bisphosphoglycerate level. Without addition of substrate the decomposition rate of this intermediate was found to be 1030 nmol/ml packed cells per 120 min. 4) The net decrease of the 2,3-bisphosphoglycerate concentration and the conversion of this compound into lactate provides a NAD regeneration system which enables the red blood cells to utilize xylitol. 5) The rate of carbon metabolism via the pentose phosphate cycle is determined by the NADPH requirement of the erythrocytes which was found to be 160 nmol/ml packed cells per 120 min under the experimental conditions employed."}
{"id": "PMID:203523", "title": "Factors involved in the modulation of cell proliferation in vivo and in vitro: the role of fibroblast and epidermal growth factors in the proliferative response of mammalian cells.", "content": "The control of proliferation of mesoderm-derived cells by EGF and FGF has been examined taking, as an example, the vascular endothelium. The mechanisms by which cell proliferation can be brought to a stop in vivo and in vitro have been reviewed.", "contents": "Factors involved in the modulation of cell proliferation in vivo and in vitro: the role of fibroblast and epidermal growth factors in the proliferative response of mammalian cells. The control of proliferation of mesoderm-derived cells by EGF and FGF has been examined taking, as an example, the vascular endothelium. The mechanisms by which cell proliferation can be brought to a stop in vivo and in vitro have been reviewed."}
{"id": "PMID:203530", "title": "Susceptibility of inbred and outbred mouse strains to Sendai virus and prevalence of infection in laboratory rodents.", "content": "Sendai virus is one of the more prevalent and serious virus infections of rodents. Infection was found in 66% of the mouse, 63% of the rat, 83% of the hamster, and 44% of the guinea pig colonies examined. Twenty-four inbred and outbred strains of mice were tested for their sensitivity to lethal Sendai virus infection. The 129/J mice tested were approximately 25,000-fold more sensitive than SJL/J mice; however, both mouse strains were similarly permissive in support of viral replication in their lung tissues. Histopathological studies revealed that whereas lesions in both sensitive and resistant mice were qualitatively similar, the lesions in the more sensitive 129/J mice appeared earlier, were much more extensive, and persisted longer than in the resistant SJL/J mice. These results suggest that the observed variance in sensitivity is not the result of a genetic restriction on virus infection and replication but rather is the result of a physiological factor(s) possibly related to some aberration of strain difference in the humoral or cell-mediated immune response.", "contents": "Susceptibility of inbred and outbred mouse strains to Sendai virus and prevalence of infection in laboratory rodents. Sendai virus is one of the more prevalent and serious virus infections of rodents. Infection was found in 66% of the mouse, 63% of the rat, 83% of the hamster, and 44% of the guinea pig colonies examined. Twenty-four inbred and outbred strains of mice were tested for their sensitivity to lethal Sendai virus infection. The 129/J mice tested were approximately 25,000-fold more sensitive than SJL/J mice; however, both mouse strains were similarly permissive in support of viral replication in their lung tissues. Histopathological studies revealed that whereas lesions in both sensitive and resistant mice were qualitatively similar, the lesions in the more sensitive 129/J mice appeared earlier, were much more extensive, and persisted longer than in the resistant SJL/J mice. These results suggest that the observed variance in sensitivity is not the result of a genetic restriction on virus infection and replication but rather is the result of a physiological factor(s) possibly related to some aberration of strain difference in the humoral or cell-mediated immune response."}
{"id": "PMID:203531", "title": "Extraction of skin test activity from Coccidioides immitis mycelia by water, perchloric acid, and aqueous phenol extraction.", "content": "Water, perchloric acid extracts, and fractions of partially defatted whole mycelia of Coccidioides immitis contained delayed skin test activity when tested in C. immitis-infected guinea pits. Aqueous phenol extraction of these fractions resulted in partitioning of activity between aqueous-soluble and phenol-soluble fractions; activity was found to be water soluble after removal of phenol by extensive dialysis. Highest specific activity skin test antigen was invariably found in the phenol-soluble phase, water-soluble fraction. Material of equivalent activity could also be extracted directly from the defatted mycelia. Skin test active fractions contained glucose, mannose, 3-O-methylmannose, glucosamine, and amino acids.", "contents": "Extraction of skin test activity from Coccidioides immitis mycelia by water, perchloric acid, and aqueous phenol extraction. Water, perchloric acid extracts, and fractions of partially defatted whole mycelia of Coccidioides immitis contained delayed skin test activity when tested in C. immitis-infected guinea pits. Aqueous phenol extraction of these fractions resulted in partitioning of activity between aqueous-soluble and phenol-soluble fractions; activity was found to be water soluble after removal of phenol by extensive dialysis. Highest specific activity skin test antigen was invariably found in the phenol-soluble phase, water-soluble fraction. Material of equivalent activity could also be extracted directly from the defatted mycelia. Skin test active fractions contained glucose, mannose, 3-O-methylmannose, glucosamine, and amino acids."}
{"id": "PMID:203532", "title": "Varicella-zoster virus: isolation and propagation in human melanoma cells at 36 and 32 degrees C.", "content": "Cell lines derived from human malignant melanoma tumors are susceptible to infection with varicella-zoster virus (VZV). Within 5 days after inoculation of vesicular fluid, cytopathic changes appeared in melanoma cell monolayer cultures that were incubated at either 36 or 32 degrees C. The VZV isolates at the two temperatures were serially propagated by passage of trypsin-dispersed infected cells. A plaque assay was developed utilizing melanoma cell monolayers overlaid with nutrient medium containing carboxymethylcellulose. By this assay method, the growth cycle of a VZV isolate propagated at 36 degrees C was studied and compared with that of another VZV isolate grown at 32 degrees C. With equivalent infected-cell inocula at a ratio on one inoculum cell to eight uninfected cells, the yield of cell-free virus at an incubation temperature of 32 degrees C was slightly higher than at 36 degrees C, although the peak occurred 60 h, rather than 36 h, postinfection. It was also found that the titer of low-passage VZV propagated at 36 degrees C was 0.5 to 1 log higher when assayed at 32 degrees C rather than at 36 degrees C.", "contents": "Varicella-zoster virus: isolation and propagation in human melanoma cells at 36 and 32 degrees C. Cell lines derived from human malignant melanoma tumors are susceptible to infection with varicella-zoster virus (VZV). Within 5 days after inoculation of vesicular fluid, cytopathic changes appeared in melanoma cell monolayer cultures that were incubated at either 36 or 32 degrees C. The VZV isolates at the two temperatures were serially propagated by passage of trypsin-dispersed infected cells. A plaque assay was developed utilizing melanoma cell monolayers overlaid with nutrient medium containing carboxymethylcellulose. By this assay method, the growth cycle of a VZV isolate propagated at 36 degrees C was studied and compared with that of another VZV isolate grown at 32 degrees C. With equivalent infected-cell inocula at a ratio on one inoculum cell to eight uninfected cells, the yield of cell-free virus at an incubation temperature of 32 degrees C was slightly higher than at 36 degrees C, although the peak occurred 60 h, rather than 36 h, postinfection. It was also found that the titer of low-passage VZV propagated at 36 degrees C was 0.5 to 1 log higher when assayed at 32 degrees C rather than at 36 degrees C."}
{"id": "PMID:203533", "title": "Enhanced resistance against encephalomyocarditis virus infection in mice, induced by a nonviable Mycobacterium tuberculosis oil-droplet vaccine.", "content": "Female C57B1/10 mice injected intravenously (i.v.) with nonviable Mycobacterium tuberculosis Jamaica cells associated with oil-droplet emulsions (WCV) were highly resistant to the i.v. injection of encephalomyocarditis virus (EMCV). Resistance to infection (87% survival) was detected from 1 week to at least 12 weeks after injection of WCV. Mice vaccinated i.v. also were resistant to intraperitoneal, subcutaneous, or intramuscular virus challenge, but were not resistant to intracranial challenge. Mice vaccinated intraperitoneally also were resistant to virus infection, whereas WCV administered intramuscularly or subcutaneously did not protect mice from virus injected by any route. Less than 50% of WCV mice that survived virus challenge possessed serum anti-EMCV-neutralizing antibody (less than 1:10), and none had detectable (less than 1:10) serum interferon. Interferon was not detected in sera of WCV mice from 4 to 144 h after i.v. injection of EMCV. Studies concerning the effects of WCV on EMCV infection suggest that mice may be protected by mechanisms that inhibit early viral replication and spread of virus to the central nervous system.", "contents": "Enhanced resistance against encephalomyocarditis virus infection in mice, induced by a nonviable Mycobacterium tuberculosis oil-droplet vaccine. Female C57B1/10 mice injected intravenously (i.v.) with nonviable Mycobacterium tuberculosis Jamaica cells associated with oil-droplet emulsions (WCV) were highly resistant to the i.v. injection of encephalomyocarditis virus (EMCV). Resistance to infection (87% survival) was detected from 1 week to at least 12 weeks after injection of WCV. Mice vaccinated i.v. also were resistant to intraperitoneal, subcutaneous, or intramuscular virus challenge, but were not resistant to intracranial challenge. Mice vaccinated intraperitoneally also were resistant to virus infection, whereas WCV administered intramuscularly or subcutaneously did not protect mice from virus injected by any route. Less than 50% of WCV mice that survived virus challenge possessed serum anti-EMCV-neutralizing antibody (less than 1:10), and none had detectable (less than 1:10) serum interferon. Interferon was not detected in sera of WCV mice from 4 to 144 h after i.v. injection of EMCV. Studies concerning the effects of WCV on EMCV infection suggest that mice may be protected by mechanisms that inhibit early viral replication and spread of virus to the central nervous system."}
{"id": "PMID:203534", "title": "Changes in liver and L-cell plasma membranes during infection with Coxiella burnetii.", "content": "Changes in plasma membrane proteins of guinea pig liver and L-929 cells were studied during infection with Coxiella burnetii. Polypeptide species resolved by disc polyacrylamide gel electrophoresis with sodium dodecyl sulfate showed quantitative but no qualitative differences between uninfected and infected samples. When the O'Farrell technique of isoelectric focusing, followed by sodium dodecyl sulfate-slab gel polyacrylamide gel electrophoresis, was employed, additional polypeptides were resolved. Livers and L cells were labeled with [3H]-glucosamine. Infected livers incorporated less [3H]glucosamine in the membrane proteins than uninfected material, presumably indicating lower glycoprotein levels. Infected L-cell membranes incorporated greater amounts of [3H]glucosamine, and also were labeled to a greater extent than uninfected membranes, employing the [125I]lactoperoxidase technique. Uninfected L cells showed a greater agglutinability with concanavalin A than did infected cells. Infected livers had much greater levels of cyclic adenosine 3',5'-monophosphate. The data indicate changes in plasma membranes as a result of infection. Possible physiological consequences of membrane changes are discussed.", "contents": "Changes in liver and L-cell plasma membranes during infection with Coxiella burnetii. Changes in plasma membrane proteins of guinea pig liver and L-929 cells were studied during infection with Coxiella burnetii. Polypeptide species resolved by disc polyacrylamide gel electrophoresis with sodium dodecyl sulfate showed quantitative but no qualitative differences between uninfected and infected samples. When the O'Farrell technique of isoelectric focusing, followed by sodium dodecyl sulfate-slab gel polyacrylamide gel electrophoresis, was employed, additional polypeptides were resolved. Livers and L cells were labeled with [3H]-glucosamine. Infected livers incorporated less [3H]glucosamine in the membrane proteins than uninfected material, presumably indicating lower glycoprotein levels. Infected L-cell membranes incorporated greater amounts of [3H]glucosamine, and also were labeled to a greater extent than uninfected membranes, employing the [125I]lactoperoxidase technique. Uninfected L cells showed a greater agglutinability with concanavalin A than did infected cells. Infected livers had much greater levels of cyclic adenosine 3',5'-monophosphate. The data indicate changes in plasma membranes as a result of infection. Possible physiological consequences of membrane changes are discussed."}
{"id": "PMID:203535", "title": "Phytohemagglutinin enhancement of dengue-2 virus replication in nonimmune rhesus monkey peripheral blood leukocytes.", "content": "Phytohemagglutinin treatment of peripheral blood leukocytes from dengue nonimmune monkeys enhanced dengue-2 virus replication. Enhancement was due primarily to an increase in the number of infected cells. Destruction of mononuclear phagocytes with silica did not significantly inhibit virus replication in phytohemagglutinin-treated cultures. Pokeweed mitogen, concanavalin A, and streptolysin O stimulated increased deoxyribonucleic acid synthesis in monkey leukocytes but did not enhance virus replication. None of the mitogens significantly affected virus replication in cultures of dengue-immune monkey peripheral blood leukocytes.", "contents": "Phytohemagglutinin enhancement of dengue-2 virus replication in nonimmune rhesus monkey peripheral blood leukocytes. Phytohemagglutinin treatment of peripheral blood leukocytes from dengue nonimmune monkeys enhanced dengue-2 virus replication. Enhancement was due primarily to an increase in the number of infected cells. Destruction of mononuclear phagocytes with silica did not significantly inhibit virus replication in phytohemagglutinin-treated cultures. Pokeweed mitogen, concanavalin A, and streptolysin O stimulated increased deoxyribonucleic acid synthesis in monkey leukocytes but did not enhance virus replication. None of the mitogens significantly affected virus replication in cultures of dengue-immune monkey peripheral blood leukocytes."}
{"id": "PMID:203536", "title": "Macrophages and age-dependent resistance to hepatitis induced by herpes simplex virus type 2 im mice.", "content": "An age-dependent increase in the resistance of BALB/c mice to induction of focal necrotic hepatitis by herpes simplex virus type 2 was demonstrated. In 3-week-old mice inoculated intraperitoneally with virus, numerous necrotic foci developed in the liver. As the mice matured, the number of lesions declined until the age of 8 weeks, when no further increase in resistance appeared. Corresponding to this, the virus titers of livers and spleens of 3-week-old mice were higher than in 8-week-old animals throughout the infection, and the infection was apparently terminated in these organs of the adult mice by day 5. In vitro infection of peritoneal macrophages from 3-week-old and 8-week-old mice showed that this age-related resistance was concomitant with an increased restriction of virus replication in peritoneal macrophages from adult mice. Since, furthermore, the resistance of adult mice could be abolished by intravenous inoculation of the macrophage-toxic agent silica before infection, and since adoptive transfer of 2 X 10(6) syngeneic macrophages from adult mice to young ones conferred to the latter a resistance comparable to that of the adult mice, it is concluded that macrophage maturation is responsible for the age-dependent resistance seen in this infection.", "contents": "Macrophages and age-dependent resistance to hepatitis induced by herpes simplex virus type 2 im mice. An age-dependent increase in the resistance of BALB/c mice to induction of focal necrotic hepatitis by herpes simplex virus type 2 was demonstrated. In 3-week-old mice inoculated intraperitoneally with virus, numerous necrotic foci developed in the liver. As the mice matured, the number of lesions declined until the age of 8 weeks, when no further increase in resistance appeared. Corresponding to this, the virus titers of livers and spleens of 3-week-old mice were higher than in 8-week-old animals throughout the infection, and the infection was apparently terminated in these organs of the adult mice by day 5. In vitro infection of peritoneal macrophages from 3-week-old and 8-week-old mice showed that this age-related resistance was concomitant with an increased restriction of virus replication in peritoneal macrophages from adult mice. Since, furthermore, the resistance of adult mice could be abolished by intravenous inoculation of the macrophage-toxic agent silica before infection, and since adoptive transfer of 2 X 10(6) syngeneic macrophages from adult mice to young ones conferred to the latter a resistance comparable to that of the adult mice, it is concluded that macrophage maturation is responsible for the age-dependent resistance seen in this infection."}
{"id": "PMID:203537", "title": "Requirement for macrophages for interferon to be effective against encephalomyocarditis virus infection of mice.", "content": "Suppression of macrophages in mice by treatments with silica or auro-thiomalate (Myocrisin) reduced production of serum interferon by polyriboinosinic acid:polyribocytidylic acid by 85 to 90%, indicating that this double-stranded polynucleotide caused interferon production primarily in macrophages. Suppression of macrophages in mice by silica or Myocrisin treatment did not significantly affect the susceptibility of mice to encephalomyocarditis virus, although at virus doses around 20 times the 50% lethal dose they died about 48 h earlier. Macrophage interferon protected mice from encephalomyocarditis virus infection at much lower doses than fibroblast interferon, and treatment of mice with silica or Myocrisin abolished the protection conferred by macrophage interferon, whereas these treatments had a much smaller effect on the protection afforded by fibroblast interferon. The requirement for macrophages for interferon to be effective in mice can explain why macrophage suppression can cause normally nonlethal viruses to kill adult mice.", "contents": "Requirement for macrophages for interferon to be effective against encephalomyocarditis virus infection of mice. Suppression of macrophages in mice by treatments with silica or auro-thiomalate (Myocrisin) reduced production of serum interferon by polyriboinosinic acid:polyribocytidylic acid by 85 to 90%, indicating that this double-stranded polynucleotide caused interferon production primarily in macrophages. Suppression of macrophages in mice by silica or Myocrisin treatment did not significantly affect the susceptibility of mice to encephalomyocarditis virus, although at virus doses around 20 times the 50% lethal dose they died about 48 h earlier. Macrophage interferon protected mice from encephalomyocarditis virus infection at much lower doses than fibroblast interferon, and treatment of mice with silica or Myocrisin abolished the protection conferred by macrophage interferon, whereas these treatments had a much smaller effect on the protection afforded by fibroblast interferon. The requirement for macrophages for interferon to be effective in mice can explain why macrophage suppression can cause normally nonlethal viruses to kill adult mice."}
{"id": "PMID:203538", "title": "Variable effect of encephalomyocarditis virus on host defense mechanisms.", "content": "A number of viruses have been shown to suppress a variety of host defense mechanisms. To further define the effect of a viral infection on host resistance, a number of parameters were examined during the course of a lethal encephalomyocarditis virus infection of mice. The peripheral lymphocyte count, the induction of interferon in spleen cells by Newcastle disease virus, and the proportion of B cells in the spleen were all decreased or suppressed. In contrast, the responsiveness of spleen lymphocytes to phytohemagglutinin, the delayed-type skin hypersensitivity to dinitrofluorobenzene, and the proportion of T cells in the spleen remained normal. These results indicate that a viral infection may have divergent effects on different parameters of host resistance and emphasize the need to examine several functions before drawing conclusions about the effect of viral infections on host defense mechanisms.", "contents": "Variable effect of encephalomyocarditis virus on host defense mechanisms. A number of viruses have been shown to suppress a variety of host defense mechanisms. To further define the effect of a viral infection on host resistance, a number of parameters were examined during the course of a lethal encephalomyocarditis virus infection of mice. The peripheral lymphocyte count, the induction of interferon in spleen cells by Newcastle disease virus, and the proportion of B cells in the spleen were all decreased or suppressed. In contrast, the responsiveness of spleen lymphocytes to phytohemagglutinin, the delayed-type skin hypersensitivity to dinitrofluorobenzene, and the proportion of T cells in the spleen remained normal. These results indicate that a viral infection may have divergent effects on different parameters of host resistance and emphasize the need to examine several functions before drawing conclusions about the effect of viral infections on host defense mechanisms."}
{"id": "PMID:203540", "title": "Screening of human brain tumors for SV40-related T antigen.", "content": "A series of 39 human brain tumors has been screened for the presence or absence of SV40-related T antigen by the direct and indirect immunoperoxidase methods. Two tumors of ependymal origin (malignant ependymoma, choroid plexus papilloma) revealed markedly positive nuclear staining for T antigen both in vivo and in vitro. The relationship of these tumors to their experimental counterparts inducible by recent human papovavirus isolates is discussed.", "contents": "Screening of human brain tumors for SV40-related T antigen. A series of 39 human brain tumors has been screened for the presence or absence of SV40-related T antigen by the direct and indirect immunoperoxidase methods. Two tumors of ependymal origin (malignant ependymoma, choroid plexus papilloma) revealed markedly positive nuclear staining for T antigen both in vivo and in vitro. The relationship of these tumors to their experimental counterparts inducible by recent human papovavirus isolates is discussed."}
{"id": "PMID:203541", "title": "Type-C oncovirus isolate from human leukemic bone marrow: further in vitro and in vivo characterization.", "content": "Rabbit corneal cells transformed by a putative human type-C helper virus pseudotype of the mouse sarcoma virus produce large amounts of transforming and non-transforming viruses. The virions are antigenically related to the woolly monkey (simian) sarcoma-leukemia type-C oncovirus. Typical sarcoma virus lesions developed in newborn rats injected with virus-producing rabbit cells. Cells producing only the putative type-C helper viruses as a result of exposure to a high dilution of transforming virus stock induce lymphosarcomas after inoculation into newborn rats.", "contents": "Type-C oncovirus isolate from human leukemic bone marrow: further in vitro and in vivo characterization. Rabbit corneal cells transformed by a putative human type-C helper virus pseudotype of the mouse sarcoma virus produce large amounts of transforming and non-transforming viruses. The virions are antigenically related to the woolly monkey (simian) sarcoma-leukemia type-C oncovirus. Typical sarcoma virus lesions developed in newborn rats injected with virus-producing rabbit cells. Cells producing only the putative type-C helper viruses as a result of exposure to a high dilution of transforming virus stock induce lymphosarcomas after inoculation into newborn rats."}
{"id": "PMID:203542", "title": "Increased immunogenicity of low-antigenic rat tumors after superinfection with endogenous murine C-type virus in nude mice.", "content": "Four chemical carcinogen-induced and two polyoma-virus-induced rat tumors were repeatedly passaged through nude mice. A methylcholanthrene-induced tumor in BDIX rats (MBDB) and a polyomavirus-induced tumor in Wistar/Fu rats (PW41) became infected with endogenous mouse virus (EMV), as judged by the expression of murine C-type virus-associated gp71, p30 and p12 antigens on their cell surface. Two ethylnitrosourea-induced tumors in BDIX rats (290T and GE3A) were exposed in vitro to the supernatant of EMV-infected PW41. Subsequently, 290T but not GE3A converted to murine gp71, p30 and p12 positivity. All these successfully infected rat tumors (EMV-MBDB, EMV-PW41 and EMV-290T) became less transplantable to and more rejectable in otherwise susceptible syngeneic rats. To compare the immunogenicity of the virus-infected and non-infected tumors, syngeneic rats were immunized three times with irradiated cells, and challenged with the non-infected tumor. Wistar/Fu rats immunized with irradiated EMV-PW41 showed no improvement in PW41 rejection, compared to rats immunized with irradiated, non-infected cells. On the other hand, BDIX rats immunized with EMV-MBDB or EMV-290T rejected MBDB or 290T, respectively, with no cross-immunity, while the rats immunized with irradiated but non-infected tumors showed no significant rejection. These results indicate that EMV infection augmented the immunogenicity of non-immunogenic or only low-immunogenic rat tumors.", "contents": "Increased immunogenicity of low-antigenic rat tumors after superinfection with endogenous murine C-type virus in nude mice. Four chemical carcinogen-induced and two polyoma-virus-induced rat tumors were repeatedly passaged through nude mice. A methylcholanthrene-induced tumor in BDIX rats (MBDB) and a polyomavirus-induced tumor in Wistar/Fu rats (PW41) became infected with endogenous mouse virus (EMV), as judged by the expression of murine C-type virus-associated gp71, p30 and p12 antigens on their cell surface. Two ethylnitrosourea-induced tumors in BDIX rats (290T and GE3A) were exposed in vitro to the supernatant of EMV-infected PW41. Subsequently, 290T but not GE3A converted to murine gp71, p30 and p12 positivity. All these successfully infected rat tumors (EMV-MBDB, EMV-PW41 and EMV-290T) became less transplantable to and more rejectable in otherwise susceptible syngeneic rats. To compare the immunogenicity of the virus-infected and non-infected tumors, syngeneic rats were immunized three times with irradiated cells, and challenged with the non-infected tumor. Wistar/Fu rats immunized with irradiated EMV-PW41 showed no improvement in PW41 rejection, compared to rats immunized with irradiated, non-infected cells. On the other hand, BDIX rats immunized with EMV-MBDB or EMV-290T rejected MBDB or 290T, respectively, with no cross-immunity, while the rats immunized with irradiated but non-infected tumors showed no significant rejection. These results indicate that EMV infection augmented the immunogenicity of non-immunogenic or only low-immunogenic rat tumors."}
{"id": "PMID:203543", "title": "Immunological study of two stocks of Moloney sarcoma virus producing regressor and progressor tumors in C57BL/6 mice.", "content": "The immune response to progressor murine sarcoma virus (P-MuSV)2 and regressor murine sarcoma virus (R-MuSV) was analyzed by the radioisotopic footpad assay (FPA) for delayed hypersensitivity (DH) and by the membrane immunofluorescence assay for anti-tumor antibodies. In mice injected with P-MuSV, the footpad response remained at a low level for 7 weeks, while membrane immunofluorescence antibody titers reached their maximum levels after 5 weeks. By contrast, in mice injected with R-MuSV, the footpad response rose to a maximum by 4 weeks and membrane immunofluorescence antibody titers reached a maximum after 4 weeks. The adoptive footpad response reached its highest level in 2 weeks. A most striking difference between the P-MuSV and the R-MuSV systems was the lower immunogenicity of tumor cells induced by the P-MuSV as measured by the FPA. Considerable differences between the two stocks were also observed in oncogenic activity and tumor growth patterns. The P-MuSV contained one-tenth the amount of helper Moloney leukemia virus found in R-MuSV. Addition of more helper Moloney leukemia virus to the P-MuSV did not produce regressor tumors.", "contents": "Immunological study of two stocks of Moloney sarcoma virus producing regressor and progressor tumors in C57BL/6 mice. The immune response to progressor murine sarcoma virus (P-MuSV)2 and regressor murine sarcoma virus (R-MuSV) was analyzed by the radioisotopic footpad assay (FPA) for delayed hypersensitivity (DH) and by the membrane immunofluorescence assay for anti-tumor antibodies. In mice injected with P-MuSV, the footpad response remained at a low level for 7 weeks, while membrane immunofluorescence antibody titers reached their maximum levels after 5 weeks. By contrast, in mice injected with R-MuSV, the footpad response rose to a maximum by 4 weeks and membrane immunofluorescence antibody titers reached a maximum after 4 weeks. The adoptive footpad response reached its highest level in 2 weeks. A most striking difference between the P-MuSV and the R-MuSV systems was the lower immunogenicity of tumor cells induced by the P-MuSV as measured by the FPA. Considerable differences between the two stocks were also observed in oncogenic activity and tumor growth patterns. The P-MuSV contained one-tenth the amount of helper Moloney leukemia virus found in R-MuSV. Addition of more helper Moloney leukemia virus to the P-MuSV did not produce regressor tumors."}
{"id": "PMID:203544", "title": "Induction of EBNA precedes the first cellular S-phase after EBV-infection of human lymphocytes.", "content": "Using a combination of immunofluorescence and autoradiography, we studied the appearance of EBNA and DNA synthesis in cord-blood lymphocytes after infection with EBV derived from the B95-8 cell line. EBNA appeared between 12 and 25 h after addition of the virus. DNA synthesis was detected in EBNA-positive cells approximately 20 h after the appearance of EBNA. This shows that EBNA induction precedes the first cellular S-phase and suggests that the cells have not yet entered the cell-division cycle when EBNA appears. Little, if any, of the total DNA synthesis induced at this stage can be attributed to EBV-mediated immunologic stimulation.", "contents": "Induction of EBNA precedes the first cellular S-phase after EBV-infection of human lymphocytes. Using a combination of immunofluorescence and autoradiography, we studied the appearance of EBNA and DNA synthesis in cord-blood lymphocytes after infection with EBV derived from the B95-8 cell line. EBNA appeared between 12 and 25 h after addition of the virus. DNA synthesis was detected in EBNA-positive cells approximately 20 h after the appearance of EBNA. This shows that EBNA induction precedes the first cellular S-phase and suggests that the cells have not yet entered the cell-division cycle when EBNA appears. Little, if any, of the total DNA synthesis induced at this stage can be attributed to EBV-mediated immunologic stimulation."}
{"id": "PMID:203545", "title": "Seroepidemiological studies of human papilloma virus (HPV-1) infections.", "content": "At least two groups of human papilloma viruses can be distinguished serologically: on the one hand HPV 1-3, which are closely related but differ in the restriction enzyme pattern of their DNA, and on the other hand HPV-4. The age distributions of patients with warts induced by HPV 1-3 or by HPV-4, respectively, differ markedly. HPV 1-3 predominates between 5 and 15 years of age, whereas HPV-4 could be isolated more often between the ages of 20-25 years. The large number of HPV-1-3-induced warts in children is paralleled by a high percentage of HPV-1 antibody-positive sera in the same age group (about 50%). With increasing age the percentage of HPV-1 antibody-positive sera decline gradually. This pattern of seroreactivity was compared to that of patients with various papillomas and with several malignant tumors. There is no evidence to suggest a link between HPV 1-3 and condylomata acuminata, laryngeal papillomas or any of the malignant tumors tested.", "contents": "Seroepidemiological studies of human papilloma virus (HPV-1) infections. At least two groups of human papilloma viruses can be distinguished serologically: on the one hand HPV 1-3, which are closely related but differ in the restriction enzyme pattern of their DNA, and on the other hand HPV-4. The age distributions of patients with warts induced by HPV 1-3 or by HPV-4, respectively, differ markedly. HPV 1-3 predominates between 5 and 15 years of age, whereas HPV-4 could be isolated more often between the ages of 20-25 years. The large number of HPV-1-3-induced warts in children is paralleled by a high percentage of HPV-1 antibody-positive sera in the same age group (about 50%). With increasing age the percentage of HPV-1 antibody-positive sera decline gradually. This pattern of seroreactivity was compared to that of patients with various papillomas and with several malignant tumors. There is no evidence to suggest a link between HPV 1-3 and condylomata acuminata, laryngeal papillomas or any of the malignant tumors tested."}
{"id": "PMID:203546", "title": "Two E-rosette-forming lymphoid cell lines.", "content": "Two E-rosette (spontaneous rosette with sheep red blood cells)-forming lymphoid cell lines were established. One (HPB-ALL) was derived from a young male Japanese patient with acute lymphoblastic leukemia (ALL), and the other (HPB-MLT) was from a 62-year-old female Japanese patient with a leukemic T-lymphoid malignancy. Formation of E rosettes, absence of any immunoglobulin determinants, absence of EBNA (Epstein-Barr virus associated nuclear antigen) and very limited stimulating ability in mixed lymphocyte culture, were characteristics mostly identical with those of so far established T-cell-derived lymphoid cell lines, MOLT, CCRF-CEM, CCRF-HS-B2, RPMI-8402 and JM. Only HPB-MLT, however, has been derived from an aged patient with T-lymphoid malignancy.", "contents": "Two E-rosette-forming lymphoid cell lines. Two E-rosette (spontaneous rosette with sheep red blood cells)-forming lymphoid cell lines were established. One (HPB-ALL) was derived from a young male Japanese patient with acute lymphoblastic leukemia (ALL), and the other (HPB-MLT) was from a 62-year-old female Japanese patient with a leukemic T-lymphoid malignancy. Formation of E rosettes, absence of any immunoglobulin determinants, absence of EBNA (Epstein-Barr virus associated nuclear antigen) and very limited stimulating ability in mixed lymphocyte culture, were characteristics mostly identical with those of so far established T-cell-derived lymphoid cell lines, MOLT, CCRF-CEM, CCRF-HS-B2, RPMI-8402 and JM. Only HPB-MLT, however, has been derived from an aged patient with T-lymphoid malignancy."}
{"id": "PMID:203547", "title": "Immune response of the draining and distal lymph nodes during the progressive grwoth of a chemically-induced transplantable rat hepatoma.", "content": "The immunological and histological changes occurring in the lymph node draining the site of a progressively growing intramuscular tumour (D192A) implant were monitored during a 4-week time course. Cell-mediated cytotoxicity against hepatoma-D192A and 15-day rat embryo cell targets, was detected with cells derived from the draining \"lumbar\" lymph node 4 days after tumour implantation and persisted up to the 2nd week of tumour growth, decreasing rapidly during the 3rd week. The observed lymph-node anergy demonstrated in cytotoxicity tests correlated with the histological findings, in that an initial marked paracortical (T-dependent) response also declined towards the end of the 3rd week of tumour growth. The B-dependent cortex showed active lymphocyte follicles in the 2nd week of the time course, and plasma-cell production continued until the experiment was terminated. These changes were shown to occur with the progressive increase in lymph-node mass. Serum antibody specific for the developing tumour was detected during the latter stages of tumour growth. The immunological and histological changes displayed were out of phase with those shown by the draining lymph node.", "contents": "Immune response of the draining and distal lymph nodes during the progressive grwoth of a chemically-induced transplantable rat hepatoma. The immunological and histological changes occurring in the lymph node draining the site of a progressively growing intramuscular tumour (D192A) implant were monitored during a 4-week time course. Cell-mediated cytotoxicity against hepatoma-D192A and 15-day rat embryo cell targets, was detected with cells derived from the draining \"lumbar\" lymph node 4 days after tumour implantation and persisted up to the 2nd week of tumour growth, decreasing rapidly during the 3rd week. The observed lymph-node anergy demonstrated in cytotoxicity tests correlated with the histological findings, in that an initial marked paracortical (T-dependent) response also declined towards the end of the 3rd week of tumour growth. The B-dependent cortex showed active lymphocyte follicles in the 2nd week of the time course, and plasma-cell production continued until the experiment was terminated. These changes were shown to occur with the progressive increase in lymph-node mass. Serum antibody specific for the developing tumour was detected during the latter stages of tumour growth. The immunological and histological changes displayed were out of phase with those shown by the draining lymph node."}
{"id": "PMID:203548", "title": "Relationship between Moloney MSV tumor resistance and endogenous virogene expression in AKR mouse strain and its hybrids.", "content": "We have examined the induction of Moloney-MSV tumors in AKR and other mouse strains in relation to endogenous virus expression. All virus-free strains so far tested were tumor-susceptible, while AKR was resistant. The selectivity of MSV tumor resistance, characteristic of AKR mice, was associated with AKR virogens segregation in first backcross to MuLV-negative/MSV-susceptible mice, and in a few second backcross families. Stronger evidence that AKR ecotropic virogene expression is the major, but not the sole, determinant of M-MSV tumor resistance in AKR mice was obtained in strains partially congeneic for akv-2 viral gene and in recombinant inbred lines derived from an original cross between AKR and C57L mice. These mice or lines, in which inheritance of endogenous viral genes had occurred, at the same time inherited the ability to show strong resistance to tumor induction by an exogenous oncogenic virus. This finding suggests that ecotropic endogenous viruses can exert a beneficial effect in their hosts providing some protective functions. Although the association between AKR-MuLV and M-MSV resistance is definite, the mechanisms by which MuLV+ mice are refractory to M-MSV tumors have still to be elucidated.", "contents": "Relationship between Moloney MSV tumor resistance and endogenous virogene expression in AKR mouse strain and its hybrids. We have examined the induction of Moloney-MSV tumors in AKR and other mouse strains in relation to endogenous virus expression. All virus-free strains so far tested were tumor-susceptible, while AKR was resistant. The selectivity of MSV tumor resistance, characteristic of AKR mice, was associated with AKR virogens segregation in first backcross to MuLV-negative/MSV-susceptible mice, and in a few second backcross families. Stronger evidence that AKR ecotropic virogene expression is the major, but not the sole, determinant of M-MSV tumor resistance in AKR mice was obtained in strains partially congeneic for akv-2 viral gene and in recombinant inbred lines derived from an original cross between AKR and C57L mice. These mice or lines, in which inheritance of endogenous viral genes had occurred, at the same time inherited the ability to show strong resistance to tumor induction by an exogenous oncogenic virus. This finding suggests that ecotropic endogenous viruses can exert a beneficial effect in their hosts providing some protective functions. Although the association between AKR-MuLV and M-MSV resistance is definite, the mechanisms by which MuLV+ mice are refractory to M-MSV tumors have still to be elucidated."}
{"id": "PMID:203549", "title": "Natural cell-mediated cytotoxicity in rats. III. Effects of immunopharmacologic treatments on natural reactivity and on reactivity augmented by polyinosinic-polycytidylic acid.", "content": "Treatment of rats with high doses of hydrocortisone, X-irradiation, or cyclophosphamide had a suppressive effect on natural cytotoxicity in vivo. However, when rats were given poly I:C after any of these agents, the levels of NK activity were similar to those in normal rats which had been given poly I:C alone. To explain these findings, we have postulated that a population of pre-NK cells, resistant to hydrocortisone, cyclophosphamide and X-irradiation was induced by poly I:C to become cytotoxic NK cells. Treatment of rats with silica, in doses that had no effect on proliferative responses of host lymphocytes to Con A in vitro, sharply diminished NK activity. With this agent, the boosting effect of poly I:C, although still detectable, was diminished. Since there is little if any indication that NK cells are phagocytic, these data suggest that phagocytes may play a role in maintaining high levels of NK activity in vivo and, further, may be involved in the mechanism by which natural cytotoxicity is boosted by poly I:C. Adult thymectomized rats had easily detectable levels of natural reactivity and the response to poly I:C was unimpaired, indicating a lack of thymic dependence for boosting as well as for spontaneous levels of NK activity.", "contents": "Natural cell-mediated cytotoxicity in rats. III. Effects of immunopharmacologic treatments on natural reactivity and on reactivity augmented by polyinosinic-polycytidylic acid. Treatment of rats with high doses of hydrocortisone, X-irradiation, or cyclophosphamide had a suppressive effect on natural cytotoxicity in vivo. However, when rats were given poly I:C after any of these agents, the levels of NK activity were similar to those in normal rats which had been given poly I:C alone. To explain these findings, we have postulated that a population of pre-NK cells, resistant to hydrocortisone, cyclophosphamide and X-irradiation was induced by poly I:C to become cytotoxic NK cells. Treatment of rats with silica, in doses that had no effect on proliferative responses of host lymphocytes to Con A in vitro, sharply diminished NK activity. With this agent, the boosting effect of poly I:C, although still detectable, was diminished. Since there is little if any indication that NK cells are phagocytic, these data suggest that phagocytes may play a role in maintaining high levels of NK activity in vivo and, further, may be involved in the mechanism by which natural cytotoxicity is boosted by poly I:C. Adult thymectomized rats had easily detectable levels of natural reactivity and the response to poly I:C was unimpaired, indicating a lack of thymic dependence for boosting as well as for spontaneous levels of NK activity."}
{"id": "PMID:203550", "title": "B-tropic oncornavirus production by BALB/c methylcholanthrene-induced sarcoma cells.", "content": "Six oncogenic cell lines were established from primary sarcomas that had been induced in thymectomized, aged, BALB/cSt mice by the injection of 3-methylcholanthrene. Of these lines, three produced B-tropic murine leukemia virus (MuLV), i.e. MuLV that would patently infect fibroblasts of BALB/c origin but not those from NIH Swiss mice. One of these lines, M-138, produced large quantities of virus, permitting the isolation of milligram quantities of B-tropic MuLV. Neonatal BALB/c mice injected with the M-138 MuLV developed high plasma levels of the species-specific virion antigen p30, but during 9 months of observation failed to manifest clinical signs of leukemia. Plasma p30 levels of NIH Swiss mice (non-permissive host) that were inoculated also as neonates with the same virus preparation, remained undetectable by radioimmunoassay. Xenotropic MuLV, i.e. that which infects cells of species other than the species of origin, was released by one of the three remaining cell lines. Two of the six original lines have remained free of detectable oncornavirus production. Our results suggest that cell lines that are stable sources of large quantities of B-tropic MuLV may be easily obtainable by the described manipulations. Equally important, however, is the fact that these data re-emphasize the danger that is inherent in assuming that a cell line is virus-free simply because it was isolated from a chemical carcinogen-induced neoplasm", "contents": "B-tropic oncornavirus production by BALB/c methylcholanthrene-induced sarcoma cells. Six oncogenic cell lines were established from primary sarcomas that had been induced in thymectomized, aged, BALB/cSt mice by the injection of 3-methylcholanthrene. Of these lines, three produced B-tropic murine leukemia virus (MuLV), i.e. MuLV that would patently infect fibroblasts of BALB/c origin but not those from NIH Swiss mice. One of these lines, M-138, produced large quantities of virus, permitting the isolation of milligram quantities of B-tropic MuLV. Neonatal BALB/c mice injected with the M-138 MuLV developed high plasma levels of the species-specific virion antigen p30, but during 9 months of observation failed to manifest clinical signs of leukemia. Plasma p30 levels of NIH Swiss mice (non-permissive host) that were inoculated also as neonates with the same virus preparation, remained undetectable by radioimmunoassay. Xenotropic MuLV, i.e. that which infects cells of species other than the species of origin, was released by one of the three remaining cell lines. Two of the six original lines have remained free of detectable oncornavirus production. Our results suggest that cell lines that are stable sources of large quantities of B-tropic MuLV may be easily obtainable by the described manipulations. Equally important, however, is the fact that these data re-emphasize the danger that is inherent in assuming that a cell line is virus-free simply because it was isolated from a chemical carcinogen-induced neoplasm"}
{"id": "PMID:203551", "title": "E.s.r. of free radicals in aqueous solutions of substituted pyrimidines.", "content": "Reactions of OH radicals with methyl and ethyl derivatives of uracil, cytosine and thymine in aqueous solutions have been investigated. Photolysis of H2O2 was used to generate OH radicals and the radicals on the base derivatives were spin-trapped using t-nitrosobutane and identified with the help of e.s.r. spectroscopy. Addition of OH radicals was found to take place predominantly to the C(5)--C(6) double bond of the bases. H-abstraction from the methyl group occurred in the N(1) methyl derivatives of uracil, cytosine and thymine. Radicals formed by H-abstraction from the methyl group were also detected for 3-methyluracil, thymine, 1-methylthymine and 1-ethylthymine. Introduction of a methyl or ethyl group at the N(1) position of uracil, cytosine and thymine causes an increase in the C(6) proton coupling and a decrease in the N(1) splitting for radicals formed by OH addition at the C(5) position.", "contents": "E.s.r. of free radicals in aqueous solutions of substituted pyrimidines. Reactions of OH radicals with methyl and ethyl derivatives of uracil, cytosine and thymine in aqueous solutions have been investigated. Photolysis of H2O2 was used to generate OH radicals and the radicals on the base derivatives were spin-trapped using t-nitrosobutane and identified with the help of e.s.r. spectroscopy. Addition of OH radicals was found to take place predominantly to the C(5)--C(6) double bond of the bases. H-abstraction from the methyl group occurred in the N(1) methyl derivatives of uracil, cytosine and thymine. Radicals formed by H-abstraction from the methyl group were also detected for 3-methyluracil, thymine, 1-methylthymine and 1-ethylthymine. Introduction of a methyl or ethyl group at the N(1) position of uracil, cytosine and thymine causes an increase in the C(6) proton coupling and a decrease in the N(1) splitting for radicals formed by OH addition at the C(5) position."}
{"id": "PMID:203554", "title": "Expression of human prostatic acid phosphatase in a pancreatic islet cell carcinoma.", "content": "The immunologic specificity of human prostatic acidphosphatase has been established by several previous investigations as well as in this study. An apparent exception to this specificity was observed--a case of pancreatic islet cell carcinoma metastasized to the liver produced acid phosphatase that was immunologically indistinguishable from the prostatic acid phosphatase. In this case, the possibility of prostatic involvement was convincingly ruled out by clinical follow-ups and by postmortem pathologic studies. Highly purified prostatic acid phosphatase and this tumor acid phosphatase exhibited very similar Km values and identical molecular weights. Immunochemical analysis of the two enzymes using antiprostatic acid phosphatase sera showed that enzymes are antigenically identical. The implications of our observation are discussed in relation to clinical application of immunoassays for prostatic phosphatase in the future and to the molecular basis of human acid phosphatase polymorphism.", "contents": "Expression of human prostatic acid phosphatase in a pancreatic islet cell carcinoma. The immunologic specificity of human prostatic acidphosphatase has been established by several previous investigations as well as in this study. An apparent exception to this specificity was observed--a case of pancreatic islet cell carcinoma metastasized to the liver produced acid phosphatase that was immunologically indistinguishable from the prostatic acid phosphatase. In this case, the possibility of prostatic involvement was convincingly ruled out by clinical follow-ups and by postmortem pathologic studies. Highly purified prostatic acid phosphatase and this tumor acid phosphatase exhibited very similar Km values and identical molecular weights. Immunochemical analysis of the two enzymes using antiprostatic acid phosphatase sera showed that enzymes are antigenically identical. The implications of our observation are discussed in relation to clinical application of immunoassays for prostatic phosphatase in the future and to the molecular basis of human acid phosphatase polymorphism."}
{"id": "PMID:203555", "title": "Surface ATPase activity at cell-cell contacts in hepatic parenchymal cells and in cAMP-treated hepatoma cells in monolayer culture.", "content": "Histochemical investigation shows that ATPase activity is located intensively on the surface of cell contacts in hepatoma cells grown in confluent monolayer culture. Dibutyryl cyclic AMP and theophylline-treated hepatoma cells which exhibit contact-inhibited growth show the absence of localization of intense ATPase activity at cell-cell contacts. However, after removal of these additives the activity fully recovers to the intense level of control cells, when the release of cells from contact inhibition of growth occurs. Cultured hepatic parenchymal cells in monolayer have little or no ATPase activity at their surface immediately after contacts are established, and again after growth to a confluent state. In a different type of hepatoma cell which is less malignant and forms a small tissue mass or island, cell surface ATPase activity at cell-cell contacts in an island is very weak or scarcely detected even when cells are not treated with dibutyryl cyclic AMP and theophylline.", "contents": "Surface ATPase activity at cell-cell contacts in hepatic parenchymal cells and in cAMP-treated hepatoma cells in monolayer culture. Histochemical investigation shows that ATPase activity is located intensively on the surface of cell contacts in hepatoma cells grown in confluent monolayer culture. Dibutyryl cyclic AMP and theophylline-treated hepatoma cells which exhibit contact-inhibited growth show the absence of localization of intense ATPase activity at cell-cell contacts. However, after removal of these additives the activity fully recovers to the intense level of control cells, when the release of cells from contact inhibition of growth occurs. Cultured hepatic parenchymal cells in monolayer have little or no ATPase activity at their surface immediately after contacts are established, and again after growth to a confluent state. In a different type of hepatoma cell which is less malignant and forms a small tissue mass or island, cell surface ATPase activity at cell-cell contacts in an island is very weak or scarcely detected even when cells are not treated with dibutyryl cyclic AMP and theophylline."}
{"id": "PMID:203558", "title": "Estimating Va/Q distributions from inert gas data with an enforced smoothing algorithm.", "content": "The accuracy of a noniterative smoothing algorithm without a nonnegativity constraint for estimating continuous Va/Q distributions from inert gas retentions was evaluated. Simulated retention measurements computed from three assumed distributions were processed by the algorithm. Original and recovered distributions were compared with the root-mean-square (rms) difference. With noise-free retentions, the rms differences were minimum with zeta = 0 (no smoothing). With simulated 3% noise, the minima occurred when 0.01 less than zeta less than 0.10. Seven trials with independent simulated errors showed a large variation in the recovered distribution and the rms difference. All recovered distributions were qualitatively different from the originals especially at low and high Va/Q values. Negative fractional flows existed in all distributions that were not grossly different from the originals. We believe that this method which did not include a nonnegativity constraint, is inappropriate for processing inert gas retentions.", "contents": "Estimating Va/Q distributions from inert gas data with an enforced smoothing algorithm. The accuracy of a noniterative smoothing algorithm without a nonnegativity constraint for estimating continuous Va/Q distributions from inert gas retentions was evaluated. Simulated retention measurements computed from three assumed distributions were processed by the algorithm. Original and recovered distributions were compared with the root-mean-square (rms) difference. With noise-free retentions, the rms differences were minimum with zeta = 0 (no smoothing). With simulated 3% noise, the minima occurred when 0.01 less than zeta less than 0.10. Seven trials with independent simulated errors showed a large variation in the recovered distribution and the rms difference. All recovered distributions were qualitatively different from the originals especially at low and high Va/Q values. Negative fractional flows existed in all distributions that were not grossly different from the originals. We believe that this method which did not include a nonnegativity constraint, is inappropriate for processing inert gas retentions."}
{"id": "PMID:203559", "title": "Autonomic blockade and coronary catecholamines and cyclic AMP in exercising man.", "content": "To assess in man the effects of autonomic blockade on the response of catecholamines in the coronary circulation to dynamic exercise, arterial and coronary sinus catecholamine concentrations were measured in six patients during supine cycling exercise, following atropine 1.8 mg and oxprenolol 0.2 mg/kg iv. Although arterial concentrations did not increase significantly, coronary sinus catecholamine concentrations increased from 2.54 +/- 0.59 nmol/1 at rest 4.44 +/- 1.3 nmol/1 during exercise (P less than 0.05; one-tailed test) and were associated with a small increase in heart rate and coronary sinus cyclic AMP concentrations from 9.4 +/- 0.7 nmol/1 (rest) to 11.6 +/- 1.1 nmol/1 (exercise) (0.05 greater than P greater than 0.01). Although autonomic blockade may have increased catecholamine release, this was not reflected in an increased efflux of catecholamines from the heart, because similar increases in coronary sinus catecholamine concentrations occurred in the absence of autonomic blockade.", "contents": "Autonomic blockade and coronary catecholamines and cyclic AMP in exercising man. To assess in man the effects of autonomic blockade on the response of catecholamines in the coronary circulation to dynamic exercise, arterial and coronary sinus catecholamine concentrations were measured in six patients during supine cycling exercise, following atropine 1.8 mg and oxprenolol 0.2 mg/kg iv. Although arterial concentrations did not increase significantly, coronary sinus catecholamine concentrations increased from 2.54 +/- 0.59 nmol/1 at rest 4.44 +/- 1.3 nmol/1 during exercise (P less than 0.05; one-tailed test) and were associated with a small increase in heart rate and coronary sinus cyclic AMP concentrations from 9.4 +/- 0.7 nmol/1 (rest) to 11.6 +/- 1.1 nmol/1 (exercise) (0.05 greater than P greater than 0.01). Although autonomic blockade may have increased catecholamine release, this was not reflected in an increased efflux of catecholamines from the heart, because similar increases in coronary sinus catecholamine concentrations occurred in the absence of autonomic blockade."}
{"id": "PMID:203560", "title": "Adrenocortical function in response to myocardial necrosis in exercise-trained rats.", "content": "Plasma corticosterone concentrations and in vitro adrenal secretion of corticosterone was determined in exercise-trained rats. Virgin, male rats, 100 days of age, were trained for an 11-wk period by treadmill running. Following the training program, rats were subjected to two subcutaneous injections of l-isoproterenol 24 h apart and killed 24 h after the second injection. All exercise-trained rats survived isoproterenol treatment, while 44% of the control rats died. Plasma corticosterone concentrations were elevated only in exercise-trained rats treated with isoproterenol. Control rats treated with isoproterenol had plasma corticosterone concentrations similar to that in control and exercise-treated rats given placebo injections. Exercise training reduced adrenocortical responsiveness to ACTH in vitro, but isoproterenol treatment increased in vitro responsiveness to ACTH in exercise-trained and control rats. Total unstimulated corticosterone secretion rates in vitro were similar. The reason for better rat survival in exercise-trained rats is unknown; however, improved energy metabolism, depressed aldosterone secretion, or both are suggested as reasons for the better survival of exercise-trained rats.", "contents": "Adrenocortical function in response to myocardial necrosis in exercise-trained rats. Plasma corticosterone concentrations and in vitro adrenal secretion of corticosterone was determined in exercise-trained rats. Virgin, male rats, 100 days of age, were trained for an 11-wk period by treadmill running. Following the training program, rats were subjected to two subcutaneous injections of l-isoproterenol 24 h apart and killed 24 h after the second injection. All exercise-trained rats survived isoproterenol treatment, while 44% of the control rats died. Plasma corticosterone concentrations were elevated only in exercise-trained rats treated with isoproterenol. Control rats treated with isoproterenol had plasma corticosterone concentrations similar to that in control and exercise-treated rats given placebo injections. Exercise training reduced adrenocortical responsiveness to ACTH in vitro, but isoproterenol treatment increased in vitro responsiveness to ACTH in exercise-trained and control rats. Total unstimulated corticosterone secretion rates in vitro were similar. The reason for better rat survival in exercise-trained rats is unknown; however, improved energy metabolism, depressed aldosterone secretion, or both are suggested as reasons for the better survival of exercise-trained rats."}
{"id": "PMID:203561", "title": "Thermally induced peripheral blood flow changes in chickens.", "content": "Changes in wattle blood flow (Q) and vascular resistance (R) were examined during both local heating of the wattle and/or general body heating of unanesthetized, male White Leghorn chickens. Q increased and R decreased during both local and general heating. Termination of heating reversed the response. Beta stimulation with isoproterenol markedly reduced R and increased Q in normothermic birds, suggesting the presence of beta receptors in the wattle vasculature. Alpha blockade with phenoxybenzamine also resulted in pronounced vasodilatation, suggesting tonic alpha-sympathetic tone in the wattle vasculature under normothermic conditions. Neither cholinergic blockade with atropine sulfate nor beta-adrenergic blockade with propranolol altered the vascular response to general heating when administered near its peak. Release of alpha-sympathetic tone is believed to subserve the response to general heating.", "contents": "Thermally induced peripheral blood flow changes in chickens. Changes in wattle blood flow (Q) and vascular resistance (R) were examined during both local heating of the wattle and/or general body heating of unanesthetized, male White Leghorn chickens. Q increased and R decreased during both local and general heating. Termination of heating reversed the response. Beta stimulation with isoproterenol markedly reduced R and increased Q in normothermic birds, suggesting the presence of beta receptors in the wattle vasculature. Alpha blockade with phenoxybenzamine also resulted in pronounced vasodilatation, suggesting tonic alpha-sympathetic tone in the wattle vasculature under normothermic conditions. Neither cholinergic blockade with atropine sulfate nor beta-adrenergic blockade with propranolol altered the vascular response to general heating when administered near its peak. Release of alpha-sympathetic tone is believed to subserve the response to general heating."}
{"id": "PMID:203562", "title": "Adaptation of the rat myocardium to endurance training.", "content": "The purpose of this study was to assess cardiac adaptation to endurance training in rats. After 11 wk of progressive treadmill exercise (1 h/day), gastrocnemius cytochrome c oxidase activity was 38% higher (P less than 0.01) in the trained (n = 20) as compared to control (n = 20) rats. Cardiac Mg2+-stimulated myofibril ATPase activity (0.308 +/- 0.012 vs. 0.324 +/- 0.006 micrometer.mg-1.min-1) did not change nor was there any change in myofibril protein concentration (60.0 +/- 1.12 vs. 59.9 +/- 0.85 mg.g-1). The isolated left ventricular papillary muscle showed no significant change in time-to-peak tension (TPT) or half-relaxation time. Tension output, however, was significantly increased with training, 2.2 +/- 0.3 vs. 1.5 +/- 0.1 g.mm-2 (P less than 0.025). Furthermore, when the papillary preparations were perfused with 0.5 mM lanthanum (La3+) to displace membrane-bound Ca2+, the time course for tension decay was significantly prolonged in the trained muscles (P less than 0.001). We conclude that endurance running of this type does not necessarily increase myofibril ATPase activity or the time course of the isometric twitch of rat papillary muscle. However, tension output per unit area does increase and this appears to be due to a greater amount of Ca2+ being made available to the contractile apparatus.", "contents": "Adaptation of the rat myocardium to endurance training. The purpose of this study was to assess cardiac adaptation to endurance training in rats. After 11 wk of progressive treadmill exercise (1 h/day), gastrocnemius cytochrome c oxidase activity was 38% higher (P less than 0.01) in the trained (n = 20) as compared to control (n = 20) rats. Cardiac Mg2+-stimulated myofibril ATPase activity (0.308 +/- 0.012 vs. 0.324 +/- 0.006 micrometer.mg-1.min-1) did not change nor was there any change in myofibril protein concentration (60.0 +/- 1.12 vs. 59.9 +/- 0.85 mg.g-1). The isolated left ventricular papillary muscle showed no significant change in time-to-peak tension (TPT) or half-relaxation time. Tension output, however, was significantly increased with training, 2.2 +/- 0.3 vs. 1.5 +/- 0.1 g.mm-2 (P less than 0.025). Furthermore, when the papillary preparations were perfused with 0.5 mM lanthanum (La3+) to displace membrane-bound Ca2+, the time course for tension decay was significantly prolonged in the trained muscles (P less than 0.001). We conclude that endurance running of this type does not necessarily increase myofibril ATPase activity or the time course of the isometric twitch of rat papillary muscle. However, tension output per unit area does increase and this appears to be due to a greater amount of Ca2+ being made available to the contractile apparatus."}
{"id": "PMID:203565", "title": "Rotavirus as a cause of diarrhea in pigs.", "content": "A rotavirus (reovirus-like agent) was associated with diarrheal diseases occurring in 1- to 4-week-old suckling pigs in 8 herds and in weaned pigs in 2 herds. Transmissible gastroenteritis virus was also detected in 2 of these herds, as was enteropathogenic Escherichia coli in 5 herds. Morbidity was generally greater than 80% in pigs of the affected age group within these herds, and mortality from diarrhea ranged from 7 to 20%. The disease due to rotavirus in suckling pigs appeared similar to the syndrome commonly referred to as milk scours, white scours, or 3-week scours. Diarrhea and villous atrophy, resembling that seen in transmissible gastroenteritis, occurred in naturally infected pigs and in gnotobiotic pigs experimentally infected with rotavirus. Diagnosis was accomplished by immune electron microscopy of intestinal contents and by immunofluorescent staining of enterocytes. A massive infection of enterocytes with rotavirus was demonstrated by immunofluorescence, which helps explain the pathogenesis of this disease. The apparent rarity of clinical rotaviral infections in suckling pigs greater than 7 days old is probably due to the acquisition of passive immunity from immune sows.", "contents": "Rotavirus as a cause of diarrhea in pigs. A rotavirus (reovirus-like agent) was associated with diarrheal diseases occurring in 1- to 4-week-old suckling pigs in 8 herds and in weaned pigs in 2 herds. Transmissible gastroenteritis virus was also detected in 2 of these herds, as was enteropathogenic Escherichia coli in 5 herds. Morbidity was generally greater than 80% in pigs of the affected age group within these herds, and mortality from diarrhea ranged from 7 to 20%. The disease due to rotavirus in suckling pigs appeared similar to the syndrome commonly referred to as milk scours, white scours, or 3-week scours. Diarrhea and villous atrophy, resembling that seen in transmissible gastroenteritis, occurred in naturally infected pigs and in gnotobiotic pigs experimentally infected with rotavirus. Diagnosis was accomplished by immune electron microscopy of intestinal contents and by immunofluorescent staining of enterocytes. A massive infection of enterocytes with rotavirus was demonstrated by immunofluorescence, which helps explain the pathogenesis of this disease. The apparent rarity of clinical rotaviral infections in suckling pigs greater than 7 days old is probably due to the acquisition of passive immunity from immune sows."}
{"id": "PMID:203567", "title": "Infectious agents associated with fetal and early neonatal death and abortion in swine.", "content": "Laboratory examination of specimens from 824 porcine abortions over a 6-year period produced 320 (38.8%) diagnoses. Viruses were involved in 22% and bacteria in 16.5% of all cases. Enterovirus was the virus isolated most often (10.9%), followed by parvovirus (4.9%), reovirus (4.4%), pseudorabies virus (1%), and adenovirus (0.8%). Leptospirosis was the bacterial infection most commonly diagnosed (9.8%), with numerous miscellaneous bacterial and fungal infections making up the remainder (7.0%) of the infectious causes.", "contents": "Infectious agents associated with fetal and early neonatal death and abortion in swine. Laboratory examination of specimens from 824 porcine abortions over a 6-year period produced 320 (38.8%) diagnoses. Viruses were involved in 22% and bacteria in 16.5% of all cases. Enterovirus was the virus isolated most often (10.9%), followed by parvovirus (4.9%), reovirus (4.4%), pseudorabies virus (1%), and adenovirus (0.8%). Leptospirosis was the bacterial infection most commonly diagnosed (9.8%), with numerous miscellaneous bacterial and fungal infections making up the remainder (7.0%) of the infectious causes."}
{"id": "PMID:203569", "title": "Cyclic AMP regulation of the hexose phosphate transport system in Escherichia coli.", "content": "Synthesis of the hexosephosphate transport system in Escherichia coli required the cyclic AMP-receptor protein regulatory complex. The apparent Km value for hexosephosphate activity was affected by the level of phosphate in the uptake environment.", "contents": "Cyclic AMP regulation of the hexose phosphate transport system in Escherichia coli. Synthesis of the hexosephosphate transport system in Escherichia coli required the cyclic AMP-receptor protein regulatory complex. The apparent Km value for hexosephosphate activity was affected by the level of phosphate in the uptake environment."}
{"id": "PMID:203570", "title": "Sequence of b cytochromes relative to ubiquinone in the electron transport chain of Escherichia coli.", "content": "A ubiquinone-deficient mutant, carrying mutations in two genes affecting ubiquinone biosynthesis, has been used, in comparison with a normal strain, to determine the sequence of some of the components of the electron transport chain of Escherichia coli. The amounts of cytochromes reduced during aerobic steady-state conditions were estimated by comparing low-temperature difference spectra of normal or ubiquinone-deficient membranes with either D-lactate or reduced nicotinamide adenine dinucleotide as substrate. From the amounts of cytochromes reduced it was concluded that ubiquinone functions at two sites, one site  being between the dehydrogenases and cytochromes and the second site being after cytochromes b562 and b556 but before cytochromes b558, d, and o. The scheme proposed is discussed in relation to the Mitchell protonmotive ubiquinone cycle.", "contents": "Sequence of b cytochromes relative to ubiquinone in the electron transport chain of Escherichia coli. A ubiquinone-deficient mutant, carrying mutations in two genes affecting ubiquinone biosynthesis, has been used, in comparison with a normal strain, to determine the sequence of some of the components of the electron transport chain of Escherichia coli. The amounts of cytochromes reduced during aerobic steady-state conditions were estimated by comparing low-temperature difference spectra of normal or ubiquinone-deficient membranes with either D-lactate or reduced nicotinamide adenine dinucleotide as substrate. From the amounts of cytochromes reduced it was concluded that ubiquinone functions at two sites, one site  being between the dehydrogenases and cytochromes and the second site being after cytochromes b562 and b556 but before cytochromes b558, d, and o. The scheme proposed is discussed in relation to the Mitchell protonmotive ubiquinone cycle."}
{"id": "PMID:203571", "title": "Mapping and characterization of the nad genes in Salmonella typhimurium LT-2.", "content": "An ampicillin enrichment technique was used to isolate 39 nicotinic acid-requiring mutants of Salmonella typhimurium LT-2. Using interrupted-mating and transductional mapping procedures, three loci, designated nadA, nadB, and nadC, were identified. These loci mapped at 33, 82, and 6 min, respectively, on the S. typhimurium linkage map. The arrangement of the loci on the Salmonella linkage map corresponded closely to the nadA, nadB, and nadC loci on the Escherichia coli K-12 linkage map, indicating that the de novo pathway to nicotinamide adenine dinucleotide and the genes governing the enzymes involved in this pathway in S. typhimurium are very similar to those in E. coli. Evidence is also presented which indicates that the product of the nadC locus in S. typhimurium LT-2 is the enzyme quinolinic acid phosphoribosyltransferase. All nadC mutants of S. typhimurium secreted between 2 and 8 mumol of quinolinic acid per 100 ml of secretion medium. In addition, none of the nadC mutants isolated were able to grow in 10(-3) M quinolinic acid, whereas all nadA and nadB mutants of S. typhimurium grew well in the presence of quinolinic acid. Transductional crosses between nadB mutants provided evidence suggestive of more than one locus in the nadB region.", "contents": "Mapping and characterization of the nad genes in Salmonella typhimurium LT-2. An ampicillin enrichment technique was used to isolate 39 nicotinic acid-requiring mutants of Salmonella typhimurium LT-2. Using interrupted-mating and transductional mapping procedures, three loci, designated nadA, nadB, and nadC, were identified. These loci mapped at 33, 82, and 6 min, respectively, on the S. typhimurium linkage map. The arrangement of the loci on the Salmonella linkage map corresponded closely to the nadA, nadB, and nadC loci on the Escherichia coli K-12 linkage map, indicating that the de novo pathway to nicotinamide adenine dinucleotide and the genes governing the enzymes involved in this pathway in S. typhimurium are very similar to those in E. coli. Evidence is also presented which indicates that the product of the nadC locus in S. typhimurium LT-2 is the enzyme quinolinic acid phosphoribosyltransferase. All nadC mutants of S. typhimurium secreted between 2 and 8 mumol of quinolinic acid per 100 ml of secretion medium. In addition, none of the nadC mutants isolated were able to grow in 10(-3) M quinolinic acid, whereas all nadA and nadB mutants of S. typhimurium grew well in the presence of quinolinic acid. Transductional crosses between nadB mutants provided evidence suggestive of more than one locus in the nadB region."}
{"id": "PMID:203575", "title": "Biological properties of islets-activating protein (IAP) purified from the culture medium of Bordetella pertussis.", "content": "The biological activities were studied of a new protein, islets-activating protein (IAP), purified from the culture medium of Bordetella pertussis. Rats injected intravenously with 1 microgram of purified IAP exhibited markedly enhanced insulin secretory responses to glucose, glucagon, epinephrine, and sulfonylureas over a period from 3 to 10 days after the injection. The degree and duration of the enhancement were proportional to the dose of IAP; the maximal effect induced by 1-2 microgram of IAP persisted for as long as 2 months. There was a highly significant correlation between the enhancement of insulin secretion and suppression of epinephrine hyperglycemia over a wide range of doses of IAP, indicating that suppression of epinephrine hyperglycemia resulted from hypoglycemic action of insulin secreted in response to epinephrine challenge. Additional actions of IAP were observed in mice; mice treated with higher doses of IAP showed symptoms were observed when lower doses of IAP were injected into mice. Thus, it is concluded that IAP is a protein primarily possessing a unique action to potentiate insulin secretory responses of experimental animals to nutritional and hormonal stimuli.", "contents": "Biological properties of islets-activating protein (IAP) purified from the culture medium of Bordetella pertussis. The biological activities were studied of a new protein, islets-activating protein (IAP), purified from the culture medium of Bordetella pertussis. Rats injected intravenously with 1 microgram of purified IAP exhibited markedly enhanced insulin secretory responses to glucose, glucagon, epinephrine, and sulfonylureas over a period from 3 to 10 days after the injection. The degree and duration of the enhancement were proportional to the dose of IAP; the maximal effect induced by 1-2 microgram of IAP persisted for as long as 2 months. There was a highly significant correlation between the enhancement of insulin secretion and suppression of epinephrine hyperglycemia over a wide range of doses of IAP, indicating that suppression of epinephrine hyperglycemia resulted from hypoglycemic action of insulin secreted in response to epinephrine challenge. Additional actions of IAP were observed in mice; mice treated with higher doses of IAP showed symptoms were observed when lower doses of IAP were injected into mice. Thus, it is concluded that IAP is a protein primarily possessing a unique action to potentiate insulin secretory responses of experimental animals to nutritional and hormonal stimuli."}
{"id": "PMID:203577", "title": "Release of glycopeptides and mucopolysaccharides from ascites hepatoma cells by tryptic treatment.", "content": "Two types of ascites hepatoma cells, AH 66 and AH 130 FN, were treated with trypsin to observe the release of complex carbohydrates constituting the plasma membranes. From AH 66 cells, mucopolysaccharide (heparan sulfate) was preferentially released. From AH 130 FN cells, N-glycosidic glycopeptides were preferentially released whereas no mucopolysaccharide (chondroitin sulfate A) was released.", "contents": "Release of glycopeptides and mucopolysaccharides from ascites hepatoma cells by tryptic treatment. Two types of ascites hepatoma cells, AH 66 and AH 130 FN, were treated with trypsin to observe the release of complex carbohydrates constituting the plasma membranes. From AH 66 cells, mucopolysaccharide (heparan sulfate) was preferentially released. From AH 130 FN cells, N-glycosidic glycopeptides were preferentially released whereas no mucopolysaccharide (chondroitin sulfate A) was released."}
{"id": "PMID:203580", "title": "The DNA untwisting enzyme from Saccharomyces cerevisiae. Partial purification and characterization.", "content": "The DNA untwisting enzyme has been partially purified from Saccharomyces cerevisiae. The enzyme exhibits a pH optimum of 7.3 to 7.6 in phosphate buffer, appears to require 0.15 M KCl for activity as determined by a DNA filter-binding assay, and is inhibited by N-ethylmaleimide. Like the untwisting enzymes from other eucaryotic cells, it can remove both positive and negative superhelical turns. A DNA molecule containing a single strand break was shown to be an intermediate in the untwisting reaction. Thermal stabilities of the enzyme from selected conditional lethal mutants defective in DNA synthesis have been examined and were found to be indistinguishable from the wild type enzyme.", "contents": "The DNA untwisting enzyme from Saccharomyces cerevisiae. Partial purification and characterization. The DNA untwisting enzyme has been partially purified from Saccharomyces cerevisiae. The enzyme exhibits a pH optimum of 7.3 to 7.6 in phosphate buffer, appears to require 0.15 M KCl for activity as determined by a DNA filter-binding assay, and is inhibited by N-ethylmaleimide. Like the untwisting enzymes from other eucaryotic cells, it can remove both positive and negative superhelical turns. A DNA molecule containing a single strand break was shown to be an intermediate in the untwisting reaction. Thermal stabilities of the enzyme from selected conditional lethal mutants defective in DNA synthesis have been examined and were found to be indistinguishable from the wild type enzyme."}
{"id": "PMID:203581", "title": "Purification and characterization of a Ca2+-binding protein in Lumbricus terrestris.", "content": "A Ca2+-binding protein which is capable of activating mammalian Ca2+-activatable cyclic nucleotide phosphodiesterase has been purified from Lumbricus terrestris and characterized. This protein and the Ca2+-dependent protein modulator from bovine tissues have many similar properties. Both proteins have molecular weights of approximately 18,000, isoelectric points of about pH 4, similar and characteristic ultraviolet spectra, and similar amino acid compositions. Both proteins bind calcium ions with high affinity. However, the protein from Lumbricus terrestris binds 2 mol of calcium ions with equal affinity, Kdiss = 6 X 10(-6) M, whereas the Ca2+-dependent protein modulator from bovine tissues binds 4 mol of calcium ions with differing affinities. Although the Ca2+-binding protein of Lumbricus terrestris activates the Ca2+-activatable cyclic nucleotide phosphodiesterase from mammalian tissues, we have failed to detect the existence of a Ca2+-activatable phosphodiesterase activity in Lumbricus terrestris. The activation of phosphodiesterase by the Ca2+-binding protein from Lumbricus terrestris is inhibited by the recently discovered bovine brain modulator binding protein (Wang, J. H., and Desai, R. (1977) J. Biol. Chem. 252, 4175-4184). Since the modulator binding protein has been shown to associate with the mammalian protein modulator to result in phosphodiesterase inhibition, it can be concluded that the Lumbricus terrestris Ca2+-binding protein also associates with the bovine brain modulator binding protein. Attempts to demonstrate the existence of a similar modulator binding protein in Lumbricus terrestris have been unsuccessful.", "contents": "Purification and characterization of a Ca2+-binding protein in Lumbricus terrestris. A Ca2+-binding protein which is capable of activating mammalian Ca2+-activatable cyclic nucleotide phosphodiesterase has been purified from Lumbricus terrestris and characterized. This protein and the Ca2+-dependent protein modulator from bovine tissues have many similar properties. Both proteins have molecular weights of approximately 18,000, isoelectric points of about pH 4, similar and characteristic ultraviolet spectra, and similar amino acid compositions. Both proteins bind calcium ions with high affinity. However, the protein from Lumbricus terrestris binds 2 mol of calcium ions with equal affinity, Kdiss = 6 X 10(-6) M, whereas the Ca2+-dependent protein modulator from bovine tissues binds 4 mol of calcium ions with differing affinities. Although the Ca2+-binding protein of Lumbricus terrestris activates the Ca2+-activatable cyclic nucleotide phosphodiesterase from mammalian tissues, we have failed to detect the existence of a Ca2+-activatable phosphodiesterase activity in Lumbricus terrestris. The activation of phosphodiesterase by the Ca2+-binding protein from Lumbricus terrestris is inhibited by the recently discovered bovine brain modulator binding protein (Wang, J. H., and Desai, R. (1977) J. Biol. Chem. 252, 4175-4184). Since the modulator binding protein has been shown to associate with the mammalian protein modulator to result in phosphodiesterase inhibition, it can be concluded that the Lumbricus terrestris Ca2+-binding protein also associates with the bovine brain modulator binding protein. Attempts to demonstrate the existence of a similar modulator binding protein in Lumbricus terrestris have been unsuccessful."}
{"id": "PMID:203584", "title": "Sarcoplasmic reticulum ATPase. Spin labeling detection of ligand-induced changes in the relative reactivities of certain sulfhydryl groups.", "content": "In sarcoplasmic reticulum fragments, chemical reactivity of calcium ATPase -SH groups toward N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)-iodoacetamide (ISL) was estimated by measuring the steady reduction in free label spectrum intensity during the labeling reaction. A few -SH groups reacted easily with ISL and activity was not inhibited. The reaction rate was highly sensitive to pH and temperature. Calcium chelation in the presence of magnesium accelerated the reaction slightly, and nucleotides accelerated if severalfold in the presence of calcium. The resulting spectra were also studied for the bound labels, after extensive washing of the nonreacted label. Compared to the spectrum obtained after labeling in the control calcium medium, the \"weakly immobilized signal\" of the spectrum of vesicles labeled in a chelated calcium medium was enhanced. On the other hand, the \"strongly immobilized signal\" was enhanced when vesicles were labeled in a medium containing calcium and nucleotides. This was taken as evidence that different -SH groups are selectively alkylated, according to the labeling medium. The present study confirms the calcium-induced modifications in the -SH environment reported previously and suggests new ways of searching for possible conformational events during the transport cycle in the membrane.", "contents": "Sarcoplasmic reticulum ATPase. Spin labeling detection of ligand-induced changes in the relative reactivities of certain sulfhydryl groups. In sarcoplasmic reticulum fragments, chemical reactivity of calcium ATPase -SH groups toward N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)-iodoacetamide (ISL) was estimated by measuring the steady reduction in free label spectrum intensity during the labeling reaction. A few -SH groups reacted easily with ISL and activity was not inhibited. The reaction rate was highly sensitive to pH and temperature. Calcium chelation in the presence of magnesium accelerated the reaction slightly, and nucleotides accelerated if severalfold in the presence of calcium. The resulting spectra were also studied for the bound labels, after extensive washing of the nonreacted label. Compared to the spectrum obtained after labeling in the control calcium medium, the \"weakly immobilized signal\" of the spectrum of vesicles labeled in a chelated calcium medium was enhanced. On the other hand, the \"strongly immobilized signal\" was enhanced when vesicles were labeled in a medium containing calcium and nucleotides. This was taken as evidence that different -SH groups are selectively alkylated, according to the labeling medium. The present study confirms the calcium-induced modifications in the -SH environment reported previously and suggests new ways of searching for possible conformational events during the transport cycle in the membrane."}
{"id": "PMID:203585", "title": "A copper-binding immunoglobulin from a myeloma patient. Purification, identification, and physical characterization.", "content": "A copper.protein complex present in the serum of a hypercupremic myeloma patient has been purified to homogeneity using gel filtration, DEAE-cellulose chromatography, and concanavalin A/Sepharose affinity chromatography. Immunoelectrophoresis and hemagglutination inhibition tests showed the copper-bound protein to be an IgG1-type immunoglobulin with lambda light chains. The immunoglobulin is of normal molecular weight (150,000) with normal size light and heavy chains (28,000 and 56,000, respectively). The carbohydrate portion of the molecule appears to be abnormal in that it interacts with concanavalin A, whereas most immunoglobulins of the gammaG-type do not. The copper in the native copper.IgG complex is in an EPR-indeterminable valence state. Copper was efficiently removed from the copper.IgG complex by dialysis against 0.1 M potassium cyanide. The apo-IgG was separated from the copper.cyanide complex by gel filtration. The copper complex was reconstituted by equilibrating the apo-IgG with 7.7 muM cupric ions.", "contents": "A copper-binding immunoglobulin from a myeloma patient. Purification, identification, and physical characterization. A copper.protein complex present in the serum of a hypercupremic myeloma patient has been purified to homogeneity using gel filtration, DEAE-cellulose chromatography, and concanavalin A/Sepharose affinity chromatography. Immunoelectrophoresis and hemagglutination inhibition tests showed the copper-bound protein to be an IgG1-type immunoglobulin with lambda light chains. The immunoglobulin is of normal molecular weight (150,000) with normal size light and heavy chains (28,000 and 56,000, respectively). The carbohydrate portion of the molecule appears to be abnormal in that it interacts with concanavalin A, whereas most immunoglobulins of the gammaG-type do not. The copper in the native copper.IgG complex is in an EPR-indeterminable valence state. Copper was efficiently removed from the copper.IgG complex by dialysis against 0.1 M potassium cyanide. The apo-IgG was separated from the copper.cyanide complex by gel filtration. The copper complex was reconstituted by equilibrating the apo-IgG with 7.7 muM cupric ions."}
{"id": "PMID:203589", "title": "Association of thymidylate kinase activity with pyrimidine deoxyribonucleoside kinase induced by herpes simplex virus.", "content": "Thymidine kinase derived from LMTK+ does not exhibit thymidylate kinase activity. However, protein isolated by affinity column chromatography from thymidine kinase-deficient mouse cells (LMTK-) infected by herpes simplex virus type 1 shows thymidylate kinase activity in addition to thymidine kinase and deoxycytidine kinase activities. The virus-induced multifunctional enzyme has a molecular weight of 85,000, whereas the molecular weight of thymidylate kinase from uninfected LMTK- mouse cells is 71,000. The virus-induced enzyme has a Km for thymidine of 0.8 micromolar, and for thymidylate of 25 micromolar, and for thymidylate of 25 micromolar; the ratio of Vmax for thymidylate kinase to thymidine kinase is 1.7. When subjected to isoelectric focusing, thymidylate kinase activity is not separated from thymidine kinase activity, and even though four peaks of activity are observed they have a constant ratio of thymidylate kinase to thymidine kinase activity. The isoelectric points (pI) of these four peaks are 4.8, 5.8, 6.2, and 6.6, respectively. Thymidylate kinase, derived from uninfected cells when subjected to isoelectric focusing, separates into a major component with an isoelectric point at pH 8.2 and a minor component at pH 7.7. Although thymidine and thymidylate kinase activities derived from the virus-infected cells cannot be separated either by affinity column chromatography, glycerol density gradient centrifugation, or isoelectric focusing, there is a differential rate of inactivation when the enzyme is subjected to incubation at 37 degrees, with thymidylate kinase activity being more labile than thymidine kinase activity.", "contents": "Association of thymidylate kinase activity with pyrimidine deoxyribonucleoside kinase induced by herpes simplex virus. Thymidine kinase derived from LMTK+ does not exhibit thymidylate kinase activity. However, protein isolated by affinity column chromatography from thymidine kinase-deficient mouse cells (LMTK-) infected by herpes simplex virus type 1 shows thymidylate kinase activity in addition to thymidine kinase and deoxycytidine kinase activities. The virus-induced multifunctional enzyme has a molecular weight of 85,000, whereas the molecular weight of thymidylate kinase from uninfected LMTK- mouse cells is 71,000. The virus-induced enzyme has a Km for thymidine of 0.8 micromolar, and for thymidylate of 25 micromolar, and for thymidylate of 25 micromolar; the ratio of Vmax for thymidylate kinase to thymidine kinase is 1.7. When subjected to isoelectric focusing, thymidylate kinase activity is not separated from thymidine kinase activity, and even though four peaks of activity are observed they have a constant ratio of thymidylate kinase to thymidine kinase activity. The isoelectric points (pI) of these four peaks are 4.8, 5.8, 6.2, and 6.6, respectively. Thymidylate kinase, derived from uninfected cells when subjected to isoelectric focusing, separates into a major component with an isoelectric point at pH 8.2 and a minor component at pH 7.7. Although thymidine and thymidylate kinase activities derived from the virus-infected cells cannot be separated either by affinity column chromatography, glycerol density gradient centrifugation, or isoelectric focusing, there is a differential rate of inactivation when the enzyme is subjected to incubation at 37 degrees, with thymidylate kinase activity being more labile than thymidine kinase activity."}
{"id": "PMID:203590", "title": "Identification of a high molecular weight presumptive precursor to albumin mRNA in the nucleus of rat liver and hepatoma cell line H4AZC2.", "content": "Nuclear RNAs prepared from rat liver and rat hepatoma cell line H4AZC2 have been fractionated and examined for albumin mRNA sequences by annealing to specific albumin [3H]cDNA. In both instances, sucrose gradient analysis revealed nuclear RNA molecules containing albumin RNA sequences which sedimented at 26 S (26 S albumin RNA). In contrast, cytoplasmic albumin messenger RNA sediments exclusively at 17 S. 26 S albumin RNA is resistant to both heat denaturation (65 degrees C X 5 min) and denaturation in 85% formamide (v/v), and 75% of these molecules are polyadenylated. These results provide evidence for the existence of an intact, high molecular weight, polyadenylated nuclear RNA which contains albumin mRNA sequences.", "contents": "Identification of a high molecular weight presumptive precursor to albumin mRNA in the nucleus of rat liver and hepatoma cell line H4AZC2. Nuclear RNAs prepared from rat liver and rat hepatoma cell line H4AZC2 have been fractionated and examined for albumin mRNA sequences by annealing to specific albumin [3H]cDNA. In both instances, sucrose gradient analysis revealed nuclear RNA molecules containing albumin RNA sequences which sedimented at 26 S (26 S albumin RNA). In contrast, cytoplasmic albumin messenger RNA sediments exclusively at 17 S. 26 S albumin RNA is resistant to both heat denaturation (65 degrees C X 5 min) and denaturation in 85% formamide (v/v), and 75% of these molecules are polyadenylated. These results provide evidence for the existence of an intact, high molecular weight, polyadenylated nuclear RNA which contains albumin mRNA sequences."}
{"id": "PMID:203591", "title": "The reduced nicotinamide adenine nucleotide-activated phosphoenolpyruvate carboxylase from Pseudomonas MA. Further studies on regulatory properties.", "content": "Phosphoenolpyruvate carboxylase from Pseudomonas MA grown on methylamine as a sole carbon source is an allosteric enzyme activated by NADH. Activation is accompanied by a change in the sedimentation value of the enzyme from 12 S to 9 S. In this paper ADP is shown to be an inhibitor of the enzyme. ADP has its most potent effect on the NADH-activated enzyme. Kinetics of ADP inhibition in the presence of NADH and of NADH activation in the presence of ADP are allosteric. The presence of ADP prevents the decrease in sedimentation value in the presence of NADH. Cross-linking studies indicate that the 12 S form of the enzyme is a tetramer of identically sized subunits and that the 9 S form corresponds to a dimer. The cross-linked enzyme is active and is activated by NADH and inhibited by ADP. It is proposed that NADH and ADP are a regulatory pair for this enzyme and reflect the energy status of the organism, allowing the carboxylase to control the flow of carbon into anabolic or catabolic pathways.", "contents": "The reduced nicotinamide adenine nucleotide-activated phosphoenolpyruvate carboxylase from Pseudomonas MA. Further studies on regulatory properties. Phosphoenolpyruvate carboxylase from Pseudomonas MA grown on methylamine as a sole carbon source is an allosteric enzyme activated by NADH. Activation is accompanied by a change in the sedimentation value of the enzyme from 12 S to 9 S. In this paper ADP is shown to be an inhibitor of the enzyme. ADP has its most potent effect on the NADH-activated enzyme. Kinetics of ADP inhibition in the presence of NADH and of NADH activation in the presence of ADP are allosteric. The presence of ADP prevents the decrease in sedimentation value in the presence of NADH. Cross-linking studies indicate that the 12 S form of the enzyme is a tetramer of identically sized subunits and that the 9 S form corresponds to a dimer. The cross-linked enzyme is active and is activated by NADH and inhibited by ADP. It is proposed that NADH and ADP are a regulatory pair for this enzyme and reflect the energy status of the organism, allowing the carboxylase to control the flow of carbon into anabolic or catabolic pathways."}
{"id": "PMID:203593", "title": "Regulation of adenosine 3':5'-monophosphate content of rous sarcoma virus-transformed human astrocytoma cells. Effects of cholera toxin on the responsiveness to catecholamines and prostaglandins.", "content": "Human astrocytoma cells (EH118MG) respond to catecholamines and prostaglandins with a marked increase in the rate of formation of cyclic AMP. Treatment of EH118MG cells with cholera toxin (10 to 100 ng/ml) for 45 to 60 min caused an increase in cellular cyclic AMP content (5- to 10-fold over basal). Cholera toxin also decreased the K0.5 for isoproterenol 10- to 50-fold and decreased the K0.5 for prostaglandin E1 (PGE1)30- to 100-fold, while increasing the maximal response to PGE1 by 1.5- to 3-fold. Treatment with cholera toxin did not change the K1 values for beta-adrenergic receptor antagonists such as propranolol, alprenolol, and sotalol. Direct binding studies using [125I]iodohydroxybenzylpindolol indicated no significant changes in the number of beta-receptors or in the kinetics of the interaction of the radioligand with receptors after treatment of cells with the toxin. Competition binding studies with propranolol and sotalol revealed no toxin-induced change in Kd values for these antagonists. Treatment with cholera toxin caused only small decreases (2- to 3-fold) in the Kd values for binding of isoproterenol and norepinephrine. It is concluded that cholera toxin has little direct effect on the binding of agonists or antagonists to beta-receptors, but instead increases the efficiency of coupling of receptor and catalytic moieties of adenylate cyclase.", "contents": "Regulation of adenosine 3':5'-monophosphate content of rous sarcoma virus-transformed human astrocytoma cells. Effects of cholera toxin on the responsiveness to catecholamines and prostaglandins. Human astrocytoma cells (EH118MG) respond to catecholamines and prostaglandins with a marked increase in the rate of formation of cyclic AMP. Treatment of EH118MG cells with cholera toxin (10 to 100 ng/ml) for 45 to 60 min caused an increase in cellular cyclic AMP content (5- to 10-fold over basal). Cholera toxin also decreased the K0.5 for isoproterenol 10- to 50-fold and decreased the K0.5 for prostaglandin E1 (PGE1)30- to 100-fold, while increasing the maximal response to PGE1 by 1.5- to 3-fold. Treatment with cholera toxin did not change the K1 values for beta-adrenergic receptor antagonists such as propranolol, alprenolol, and sotalol. Direct binding studies using [125I]iodohydroxybenzylpindolol indicated no significant changes in the number of beta-receptors or in the kinetics of the interaction of the radioligand with receptors after treatment of cells with the toxin. Competition binding studies with propranolol and sotalol revealed no toxin-induced change in Kd values for these antagonists. Treatment with cholera toxin caused only small decreases (2- to 3-fold) in the Kd values for binding of isoproterenol and norepinephrine. It is concluded that cholera toxin has little direct effect on the binding of agonists or antagonists to beta-receptors, but instead increases the efficiency of coupling of receptor and catalytic moieties of adenylate cyclase."}
{"id": "PMID:203595", "title": "Rabbit mammary prolactin receptors. Demonstration of a late puerperal increase in affinity.", "content": "Crude receptor preparations of rabbit mammary gland were made by differential centrifugation and reacted with lactoperoxidase-iodinated ovine prolactin (oPRL) in order to determine their binding characteristics. Receptors prepared from the mammary glands of animals less than 4 days postpartum bound oPRL with high affinity (Ka = 3.50 X 10(9) M-1), in good agreement with previous results of other investigators. The binding capacity of these preparations was 107 +/- 16.3 fmol/mg of protein. In contrast, receptors prepared from the mammary glands of late lactating rabbits (Days 25 to 30 of lactation) showed a 2.5-fold increase in binding affinity (Ka = 8.63 X 10(9) M-1, p less than 0.001) without a significant increase in binding capacity (135 +/- 21.4 fmol/mg, p greater than 0.2). Kinetic experiments revealed that the rates of association of hormone and receptor were identical in early and late receptor preparations, and that the 2.5-fold decrease the dissociation rate observed in the late preparations was fully explanatory of the differences in equilibrium binding. The mechanism of this affinity increase is not known. Such a change in binding characteristics, which would tend to enhance tissue responsiveness, may underlie the well characterized maintenance of full lactation in women despite falling concentrations of prolactin.", "contents": "Rabbit mammary prolactin receptors. Demonstration of a late puerperal increase in affinity. Crude receptor preparations of rabbit mammary gland were made by differential centrifugation and reacted with lactoperoxidase-iodinated ovine prolactin (oPRL) in order to determine their binding characteristics. Receptors prepared from the mammary glands of animals less than 4 days postpartum bound oPRL with high affinity (Ka = 3.50 X 10(9) M-1), in good agreement with previous results of other investigators. The binding capacity of these preparations was 107 +/- 16.3 fmol/mg of protein. In contrast, receptors prepared from the mammary glands of late lactating rabbits (Days 25 to 30 of lactation) showed a 2.5-fold increase in binding affinity (Ka = 8.63 X 10(9) M-1, p less than 0.001) without a significant increase in binding capacity (135 +/- 21.4 fmol/mg, p greater than 0.2). Kinetic experiments revealed that the rates of association of hormone and receptor were identical in early and late receptor preparations, and that the 2.5-fold decrease the dissociation rate observed in the late preparations was fully explanatory of the differences in equilibrium binding. The mechanism of this affinity increase is not known. Such a change in binding characteristics, which would tend to enhance tissue responsiveness, may underlie the well characterized maintenance of full lactation in women despite falling concentrations of prolactin."}
{"id": "PMID:203596", "title": "Nucleotide sequences of DNA encoding the 3' ends of SV40 mRNA. I. The sequence of the DNA fragment Hi-DII,III-G.", "content": "The 3' ends of the mRNA coding for the early and late proteins of SV40 DNA overlap. We have analyzed the restriction endonuclease fragment of SV40 DNA complementary to the 3' untranslated ends of the mRNA and the codons for the COOH-terminal amino acids of early and late protein. The sequence of this DNA fragment is presented.", "contents": "Nucleotide sequences of DNA encoding the 3' ends of SV40 mRNA. I. The sequence of the DNA fragment Hi-DII,III-G. The 3' ends of the mRNA coding for the early and late proteins of SV40 DNA overlap. We have analyzed the restriction endonuclease fragment of SV40 DNA complementary to the 3' untranslated ends of the mRNA and the codons for the COOH-terminal amino acids of early and late protein. The sequence of this DNA fragment is presented."}
{"id": "PMID:203597", "title": "Nucleotide sequence of DNA template for the 3' ends of SV40 mRNA. II. The sequence of the DNA fragment EcorII-F and a part of EcorII-H.", "content": "The nucleotide sequence for two-thirds of restriction endonuclease fragment EcoRII-F and part of RII-H of SV40 DNA is presented. This segment of SV40 DNA is complementary to the sequence near the 3' end of early mRNA. This sequence could be translated in one reading frame to form a large protein. However, in a second translational frame there are four AUG codons followed by 91 sense triplets, followed by a termination codon. These results provide the sequence for the entire 3' untranslated ends of SV40 early and late mRNAs and for the DNA beyond the 3' ends of the mRNAs. The ends of early and late mRNA are transcribed from the opposite strands of the same segment of DNA. At or beyond the 3' ends of both early and late mRNA are sequences whose transcripts would include uridylic acid-rich products.", "contents": "Nucleotide sequence of DNA template for the 3' ends of SV40 mRNA. II. The sequence of the DNA fragment EcorII-F and a part of EcorII-H. The nucleotide sequence for two-thirds of restriction endonuclease fragment EcoRII-F and part of RII-H of SV40 DNA is presented. This segment of SV40 DNA is complementary to the sequence near the 3' end of early mRNA. This sequence could be translated in one reading frame to form a large protein. However, in a second translational frame there are four AUG codons followed by 91 sense triplets, followed by a termination codon. These results provide the sequence for the entire 3' untranslated ends of SV40 early and late mRNAs and for the DNA beyond the 3' ends of the mRNAs. The ends of early and late mRNA are transcribed from the opposite strands of the same segment of DNA. At or beyond the 3' ends of both early and late mRNA are sequences whose transcripts would include uridylic acid-rich products."}
{"id": "PMID:203598", "title": "A deoxyribonucleic acid unwinding protein isolated from regenerating rat liver. Physical and functional properties.", "content": "A DNA-unwinding protein has been purified from regenerating rat liver cytosol to apparent homogeneity. The protein is present in about 10(6) copies per cell. It is a tetramer, composed of 25,000-dalton subunits which does not exhibit enzymatic activity for ATPase, DNA polymerase, or DNase. The protein is able to unwind the double helix of poly[d(A-T)], depressing the melting point of this synthetic polymer by about 40 degrees. It also binds to supercoiled SV40 DNA, probably by melting A-T-rich regions in the genome. The fully saturated complex of protein and SV40 DNA sediments at 30 S. Homologous DNA polymerases-alpha and -beta are stimulated by the protein at a different level depending on the templates used. This result argues in favor of the intervention of the unwinding protein in replication processes.", "contents": "A deoxyribonucleic acid unwinding protein isolated from regenerating rat liver. Physical and functional properties. A DNA-unwinding protein has been purified from regenerating rat liver cytosol to apparent homogeneity. The protein is present in about 10(6) copies per cell. It is a tetramer, composed of 25,000-dalton subunits which does not exhibit enzymatic activity for ATPase, DNA polymerase, or DNase. The protein is able to unwind the double helix of poly[d(A-T)], depressing the melting point of this synthetic polymer by about 40 degrees. It also binds to supercoiled SV40 DNA, probably by melting A-T-rich regions in the genome. The fully saturated complex of protein and SV40 DNA sediments at 30 S. Homologous DNA polymerases-alpha and -beta are stimulated by the protein at a different level depending on the templates used. This result argues in favor of the intervention of the unwinding protein in replication processes."}
{"id": "PMID:203600", "title": "Cell contact-induced inhibition of division in Dictyostelium.", "content": "The developmental stage at which Dictyostelium discoideum strain v12/M2 cells was inhibited in resuming cell division was monitored by a Coulter counter. Neither vegetative nor pre-aggregating v12/M2 amoebae used as inocula in liquid growth cultures exhibited a delay in recommencing cell division. Inocula prepared from aggregates were delayed for 3 h before the onset of division. Although cyclic AMP had no effect upon vegetative or preaggregating stages the aggregating amoebae were inhibited for 9 h before resuming division. Following the onset of division by both controls and cyclic AMP-treated cells the normal growth rate of vegetative amoebae (3.2 h/generation) was attained. Aggregateless mutant vegetative amoebae and those of comparable ages to vas/M2 aggregates were not inhibited in the rate of cell division by cyclic AMP. Cyclic AMP sustains the delay in cell division only among amoebae derived from aggregates. Cyclic AMP induces structural components in the plasma membranes which may be necessary in cell adhesion and interactions. Consequently interactions between the membranes of apposing cells may transmit stimuli intracellularly to inhibit cell division.", "contents": "Cell contact-induced inhibition of division in Dictyostelium. The developmental stage at which Dictyostelium discoideum strain v12/M2 cells was inhibited in resuming cell division was monitored by a Coulter counter. Neither vegetative nor pre-aggregating v12/M2 amoebae used as inocula in liquid growth cultures exhibited a delay in recommencing cell division. Inocula prepared from aggregates were delayed for 3 h before the onset of division. Although cyclic AMP had no effect upon vegetative or preaggregating stages the aggregating amoebae were inhibited for 9 h before resuming division. Following the onset of division by both controls and cyclic AMP-treated cells the normal growth rate of vegetative amoebae (3.2 h/generation) was attained. Aggregateless mutant vegetative amoebae and those of comparable ages to vas/M2 aggregates were not inhibited in the rate of cell division by cyclic AMP. Cyclic AMP sustains the delay in cell division only among amoebae derived from aggregates. Cyclic AMP induces structural components in the plasma membranes which may be necessary in cell adhesion and interactions. Consequently interactions between the membranes of apposing cells may transmit stimuli intracellularly to inhibit cell division."}
{"id": "PMID:203601", "title": "Eradication of Aleutian disease of mink by eliminating positive counterimmunoelectrophoresis test reactors.", "content": "The counterimmunoelectrophorsis test was applied on three Aleutian disease virus-infected mink ranches for the detection of specific Aleutian disease virus antibody. All mink on the ranches were tested during the pelting season and before the breeding season for 4 consecutive years. Aleutian disease has been eliminated from the three commercial mink ranches by culling out all mink that were positive for Aleutian disease virus antibody.", "contents": "Eradication of Aleutian disease of mink by eliminating positive counterimmunoelectrophoresis test reactors. The counterimmunoelectrophorsis test was applied on three Aleutian disease virus-infected mink ranches for the detection of specific Aleutian disease virus antibody. All mink on the ranches were tested during the pelting season and before the breeding season for 4 consecutive years. Aleutian disease has been eliminated from the three commercial mink ranches by culling out all mink that were positive for Aleutian disease virus antibody."}
{"id": "PMID:203602", "title": "Detection of alcohols and volatile fatty acids by head-space gas chromatography in identification of anaerobic bacteria.", "content": "A head-space gas chromatographic technique for the analysis of volatile bacterial metabolites is described. Bacteroides fragilis, Clostridium perfringens, and Propionibacterium acnes, cultured in a glucose-containing peptone yeast extract medium, were studied. The head-space technique was compared with the injection of the complete liquid culture medium, and solvent extracts thereof, into the gas chromatograph. Volatile fatty acids could be detected by all three methods, whereas alcohols produced by C. perfringens and P. acnes were detectable only in the head-space chromatograms. Both FFAP and Porapak Q were used as gas chromatography stationary phase. Porapak Q was found more suitable than FFAP for the separation of alcohols. The head-space technique requires a minimum of preparation before the analysis and is well suited to automation.", "contents": "Detection of alcohols and volatile fatty acids by head-space gas chromatography in identification of anaerobic bacteria. A head-space gas chromatographic technique for the analysis of volatile bacterial metabolites is described. Bacteroides fragilis, Clostridium perfringens, and Propionibacterium acnes, cultured in a glucose-containing peptone yeast extract medium, were studied. The head-space technique was compared with the injection of the complete liquid culture medium, and solvent extracts thereof, into the gas chromatograph. Volatile fatty acids could be detected by all three methods, whereas alcohols produced by C. perfringens and P. acnes were detectable only in the head-space chromatograms. Both FFAP and Porapak Q were used as gas chromatography stationary phase. Porapak Q was found more suitable than FFAP for the separation of alcohols. The head-space technique requires a minimum of preparation before the analysis and is well suited to automation."}
{"id": "PMID:203603", "title": "Production of human lymphoblastoid interferon by Namalva cells.", "content": "Optimum conditions for growth and interferon production by a human lymphoblastoid cell line, Namalva, have been studied. Adaptation to large-scale production is possible utilizing either Sendai virus or Newcastle disease virus. Priming of cultures before induction is unnecessary. The interferon produced has properties similar to human leukocyte interferon. The production of lymphoblastoid interferon per cell is increased two- to fourfold after dilution with serum-free medium of a saturation-density culture of Namalva induced with Newcastle disease virus. Maximum interferon yields were obtained 27 h after the addition of virus, using cultures diluted to 4 X 10(5) to 9 X 10(5) cells per ml. The presence of glutamine in the dilution medium was required for maximum interferon production. Newcastle disease virus appeared to inhibit the rates of RNA and protein synthesis more effectively in the diluted cultures.", "contents": "Production of human lymphoblastoid interferon by Namalva cells. Optimum conditions for growth and interferon production by a human lymphoblastoid cell line, Namalva, have been studied. Adaptation to large-scale production is possible utilizing either Sendai virus or Newcastle disease virus. Priming of cultures before induction is unnecessary. The interferon produced has properties similar to human leukocyte interferon. The production of lymphoblastoid interferon per cell is increased two- to fourfold after dilution with serum-free medium of a saturation-density culture of Namalva induced with Newcastle disease virus. Maximum interferon yields were obtained 27 h after the addition of virus, using cultures diluted to 4 X 10(5) to 9 X 10(5) cells per ml. The presence of glutamine in the dilution medium was required for maximum interferon production. Newcastle disease virus appeared to inhibit the rates of RNA and protein synthesis more effectively in the diluted cultures."}
{"id": "PMID:203604", "title": "Quantitation of antibodies to varicella-zoster virus by immune adherence hemagglutination.", "content": "Immune adherence hemagglutination was compared with the complement fixation test as a means of measuring antibodies to varicella-zoster virus. Analysis of acute- and convalescent-phase sera from patients infected with varicella-zoster or with herpes simplex virus showed the immune adherence hemagglutination test to be more sensitive than the complement fixation test, and greater cross-reactivity between the two viruses appeared to be associated with the increased sensitivity. The two assay methods were used to measure antibodies to varicella-zoster virus in 265 sera obtained from patients of different ages as well as sera from 26 patients with leukemia. There were 35 cases where antibodies were detected by immune adherence hemagglutination but not by complement fixation, whereas in five cases the converse was found. Our findings support the contention that immune adherence hemagglutination is the method of choice for detecting antibodies to varicella-zoster virus.", "contents": "Quantitation of antibodies to varicella-zoster virus by immune adherence hemagglutination. Immune adherence hemagglutination was compared with the complement fixation test as a means of measuring antibodies to varicella-zoster virus. Analysis of acute- and convalescent-phase sera from patients infected with varicella-zoster or with herpes simplex virus showed the immune adherence hemagglutination test to be more sensitive than the complement fixation test, and greater cross-reactivity between the two viruses appeared to be associated with the increased sensitivity. The two assay methods were used to measure antibodies to varicella-zoster virus in 265 sera obtained from patients of different ages as well as sera from 26 patients with leukemia. There were 35 cases where antibodies were detected by immune adherence hemagglutination but not by complement fixation, whereas in five cases the converse was found. Our findings support the contention that immune adherence hemagglutination is the method of choice for detecting antibodies to varicella-zoster virus."}
{"id": "PMID:203605", "title": "Viral antibodies in cerebrospinal fluid of multiple sclerosis and control patients: comparison between radioimmunoassay and conventional techniques.", "content": "Cerebrospinal fluid antibodies to measles, rubella, vaccinia, herpes simplex, and varicella-zoster viruses in four patient study groups (clinically definite multiple sclerosis [MS], early probable MS, optic neuritis, and control patients with other neurological diseases) were assayed by radioimmunoassay, complement fixation, hemagglutination-inhibition, or complement-enhanced plaque reduction methods. Antibodies were more frequently found and at higher dilutions by radioimmunoassay than by other techniques. Measles virus antibody, the most frequently found antibody, was present in the cerebrospinal fluid of 72% of MS patients and 5% of control patients. The differences between the numbers of MS patients and control patients with antibodies to other viruses were not as marked. Thus, 58% of MS patients versus 21% of control patients had antibody to rubella virus, 20 versus 3% had antibody to vaccinia virus, 50 versus 33% had antibody to herpes simplex virus, and 25 versus 8% had antibody to varicella virus. Sixty-seven percent of MS patients and 26% of control patients had antibodies to two or more viruses in their cerebrospinal fluid.", "contents": "Viral antibodies in cerebrospinal fluid of multiple sclerosis and control patients: comparison between radioimmunoassay and conventional techniques. Cerebrospinal fluid antibodies to measles, rubella, vaccinia, herpes simplex, and varicella-zoster viruses in four patient study groups (clinically definite multiple sclerosis [MS], early probable MS, optic neuritis, and control patients with other neurological diseases) were assayed by radioimmunoassay, complement fixation, hemagglutination-inhibition, or complement-enhanced plaque reduction methods. Antibodies were more frequently found and at higher dilutions by radioimmunoassay than by other techniques. Measles virus antibody, the most frequently found antibody, was present in the cerebrospinal fluid of 72% of MS patients and 5% of control patients. The differences between the numbers of MS patients and control patients with antibodies to other viruses were not as marked. Thus, 58% of MS patients versus 21% of control patients had antibody to rubella virus, 20 versus 3% had antibody to vaccinia virus, 50 versus 33% had antibody to herpes simplex virus, and 25 versus 8% had antibody to varicella virus. Sixty-seven percent of MS patients and 26% of control patients had antibodies to two or more viruses in their cerebrospinal fluid."}
{"id": "PMID:203606", "title": "Serotyping herpes simplex virus isolated by enzyme-linked immunosorbent assays.", "content": "An enzyme-linked immunosorbent assay (ELISA) using a double-antibody sandwich tecnhique has been developed to serotype isolates of herpes simplex virus from clinical sources. The results obtained using this procedure were in agreement with those obtained with a standard neutralization test in typing stock cultures and 32 clinical isolates of herpes simplex virus. Clear differentiation between the two viral serotypes was obtained using rabbit immunoglobulin cross-absorbed with heterologous virus antigen. The ELISA procedure described appears to be a convenient and accurate substitute for the neutralization test in typing herpes simplex viruses. ELISA techniques require relatively small amounts of antigen and antibody and can be performed with very simple equipment.", "contents": "Serotyping herpes simplex virus isolated by enzyme-linked immunosorbent assays. An enzyme-linked immunosorbent assay (ELISA) using a double-antibody sandwich tecnhique has been developed to serotype isolates of herpes simplex virus from clinical sources. The results obtained using this procedure were in agreement with those obtained with a standard neutralization test in typing stock cultures and 32 clinical isolates of herpes simplex virus. Clear differentiation between the two viral serotypes was obtained using rabbit immunoglobulin cross-absorbed with heterologous virus antigen. The ELISA procedure described appears to be a convenient and accurate substitute for the neutralization test in typing herpes simplex viruses. ELISA techniques require relatively small amounts of antigen and antibody and can be performed with very simple equipment."}
{"id": "PMID:203607", "title": "Rapid identification of Neisseria gonorrhoeae and Neisseria meningitidis by using enzymatic profiles.", "content": "The enzymatic profiles of Neisseria gonorrhoeae, N. meningitidis, and related species were determined, using a total of 48 chromogenic substrates. Enzyme classes assayed for included glycosidases, aminopeptidases, phosphoamidases, proteases, lipases, esterases, and aryl sulfatase. A final test selection of 10 substrates, based upon their differential and reproducible characteristics, allowed the separation of N. gonorrhoeae and N. meningitidis from each other and from all species tested within 4 h after primary isolation on modified Thayer-Martin medium. The need for subculturing suspect colonies from modified Thayer-Martin medium to chocolate medium with a subsequent loss of 18 to 24 h of identification is eliminated.", "contents": "Rapid identification of Neisseria gonorrhoeae and Neisseria meningitidis by using enzymatic profiles. The enzymatic profiles of Neisseria gonorrhoeae, N. meningitidis, and related species were determined, using a total of 48 chromogenic substrates. Enzyme classes assayed for included glycosidases, aminopeptidases, phosphoamidases, proteases, lipases, esterases, and aryl sulfatase. A final test selection of 10 substrates, based upon their differential and reproducible characteristics, allowed the separation of N. gonorrhoeae and N. meningitidis from each other and from all species tested within 4 h after primary isolation on modified Thayer-Martin medium. The need for subculturing suspect colonies from modified Thayer-Martin medium to chocolate medium with a subsequent loss of 18 to 24 h of identification is eliminated."}
{"id": "PMID:203608", "title": "Incidence in South-west Scotland of hepatitis B surface antigen in the liver of patients with hepatocellular carcinoma.", "content": "A retrospective examination in South-west Scotland of formalin-fixed paraffin-embedded liver tissue by an immunoperoxidase technique revealed hepatitis B surface antigen (HBsAg) in eight out of 81 cases (10%) of primary hepatocellular carcinoma (PHC) and in four out of 82 cases (5%) of cirrhosis. No positive staining was found in 112 controls without overt liver disease matched for age and sex. Unlike most previous studies showing an association between HBsAg and PHC, the present investigation was carried out in an area where HBs antigenaemia is infrequent and PHC is an uncommon tumour. While possibly hepatitis infection is an important cause of PHC, the association between HBsAg and PHC could be due merely to activation by the tumour of latent virus B in a previously infected person.", "contents": "Incidence in South-west Scotland of hepatitis B surface antigen in the liver of patients with hepatocellular carcinoma. A retrospective examination in South-west Scotland of formalin-fixed paraffin-embedded liver tissue by an immunoperoxidase technique revealed hepatitis B surface antigen (HBsAg) in eight out of 81 cases (10%) of primary hepatocellular carcinoma (PHC) and in four out of 82 cases (5%) of cirrhosis. No positive staining was found in 112 controls without overt liver disease matched for age and sex. Unlike most previous studies showing an association between HBsAg and PHC, the present investigation was carried out in an area where HBs antigenaemia is infrequent and PHC is an uncommon tumour. While possibly hepatitis infection is an important cause of PHC, the association between HBsAg and PHC could be due merely to activation by the tumour of latent virus B in a previously infected person."}
{"id": "PMID:203609", "title": "'Pseudocirrhosis' in hereditary haemorrhagic telangiectasia.", "content": "Telangiectasia-associated hepatic fibrosis (TAHF) in a 68-year-old woman with hereditary haemorrhagic telangiectasia (HHT) is described. The patient died of oat-cell carcinoma of the lung. In addition to the structural alterations which have been described previously in HHT, the liver exhibited focal midlobular hepatocytic necrosis and tumour metastases. The possibility that treatment of HHT was causally related to some of the hepatic abnormalities found in our patient and the differentiation of TAHF from true cirrhosis are discussed.", "contents": "'Pseudocirrhosis' in hereditary haemorrhagic telangiectasia. Telangiectasia-associated hepatic fibrosis (TAHF) in a 68-year-old woman with hereditary haemorrhagic telangiectasia (HHT) is described. The patient died of oat-cell carcinoma of the lung. In addition to the structural alterations which have been described previously in HHT, the liver exhibited focal midlobular hepatocytic necrosis and tumour metastases. The possibility that treatment of HHT was causally related to some of the hepatic abnormalities found in our patient and the differentiation of TAHF from true cirrhosis are discussed."}
{"id": "PMID:203610", "title": "ACTH and ACTH4-10 modification of neophobia and taste aversion responses in the rat.", "content": "A series of experiments assessed the effects of ACTH and the ACTH analogue ACTH4-10 on drinking in conditioned taste aversion and neophobic situations. Both substances delayed the extinction of a conditioned taste aversion established by a single pairing of lithium chloride with milk (Experiment 1). However, in this situation, the ACTH parent peptide was more potent behaviorally. Administration of ACTH suppressed milk consumption in animals with no toxicosis experience (Experiment 2). This effect was apparently not due to the conditioning of a taste aversion (Experiment 3) with ACTH serving as a weak aversive unconditioned stimulus. Administration of exogenous ACTH (Experiment 4) or ACTH4-10 (Experiment 5) did not enhance neophobia; however, repeated injections of ACTH suppressed drinking. This ACTH suppression was related to the familiarity/novelty of the subtance being consumed. The neophobic response to milk eas no accompanied by pituitary-adrenal activation (Experiment 6). Both neophobic and conditioned taste aversion situation appear to be useful for assessing peptide effects on consummatory behavior.", "contents": "ACTH and ACTH4-10 modification of neophobia and taste aversion responses in the rat. A series of experiments assessed the effects of ACTH and the ACTH analogue ACTH4-10 on drinking in conditioned taste aversion and neophobic situations. Both substances delayed the extinction of a conditioned taste aversion established by a single pairing of lithium chloride with milk (Experiment 1). However, in this situation, the ACTH parent peptide was more potent behaviorally. Administration of ACTH suppressed milk consumption in animals with no toxicosis experience (Experiment 2). This effect was apparently not due to the conditioning of a taste aversion (Experiment 3) with ACTH serving as a weak aversive unconditioned stimulus. Administration of exogenous ACTH (Experiment 4) or ACTH4-10 (Experiment 5) did not enhance neophobia; however, repeated injections of ACTH suppressed drinking. This ACTH suppression was related to the familiarity/novelty of the subtance being consumed. The neophobic response to milk eas no accompanied by pituitary-adrenal activation (Experiment 6). Both neophobic and conditioned taste aversion situation appear to be useful for assessing peptide effects on consummatory behavior."}
{"id": "PMID:203611", "title": "Multiple glomus tumors.", "content": "A man had widespread, slowly evolving vascular lesions since infancy suggestive of the Blue Rubber Bleb Nevus Syndrome. His son had two painless lesions typical of Multiple Glomus Tumors. Many of the man's nodular lesions were painful. Post-excision recurrences were noted. Histologic studies of asymptomatic tumors from both cases showed irregular, dilated, vascular channels surrounded by narrow mantles of glomus cells, whereas a painful tumor had large foci of glomus cells with wider mantles around the flattened channels. Electron microscopy showed the glomus cells to be modified smooth muscle cells. The anatomy and pathology of glomus tumors are reviewed. Differentiation from other syndromes of multiple hemangiomata, particularly the Blue Rubber Bleb Nevus Syndrome is stressed. It is suggested that Multiple Glomus Tumors may be derived from simple cutaneous vessels and not the Sucquet-Hoyer canal of the normal cutaneous glomus body described by Masson in 1924.", "contents": "Multiple glomus tumors. A man had widespread, slowly evolving vascular lesions since infancy suggestive of the Blue Rubber Bleb Nevus Syndrome. His son had two painless lesions typical of Multiple Glomus Tumors. Many of the man's nodular lesions were painful. Post-excision recurrences were noted. Histologic studies of asymptomatic tumors from both cases showed irregular, dilated, vascular channels surrounded by narrow mantles of glomus cells, whereas a painful tumor had large foci of glomus cells with wider mantles around the flattened channels. Electron microscopy showed the glomus cells to be modified smooth muscle cells. The anatomy and pathology of glomus tumors are reviewed. Differentiation from other syndromes of multiple hemangiomata, particularly the Blue Rubber Bleb Nevus Syndrome is stressed. It is suggested that Multiple Glomus Tumors may be derived from simple cutaneous vessels and not the Sucquet-Hoyer canal of the normal cutaneous glomus body described by Masson in 1924."}
{"id": "PMID:203612", "title": "The regulatory GTPase cycle of turkey erythrocyte adenylate cyclase.", "content": "It has recently been suggested that adenylate cyclase activity is controlled by a regulatory cycle consisting of two reactions: a hormone induced formation of the active adenylate cyclase-GTP complex, and a subsequent turn-off reaction in which hydrolysis of the bound nucleotide reverts the system to the inactive state. To test this model each of the two reactions was measured separately and their rate constants were used to estimate the steady state adenylate cyclase and GTPase activities. The first order rate constants were kon = 3 min-1 for the activation reaction and koff = 15 min-1 for the turn-off reaction. Substitution of these rate constants in the steady state equation of the regulatory cycle gave values of hormone stimulated adenylate cyclase and GTPase activities similar to those determined by direct measurements. Treatment of the adenylate cyclase with cholera toxin caused a decrease of 96% in the rate constant of the turn-off reaction. In this case too the activities calculated from the steady state equation were in good agreement with those determined directly.", "contents": "The regulatory GTPase cycle of turkey erythrocyte adenylate cyclase. It has recently been suggested that adenylate cyclase activity is controlled by a regulatory cycle consisting of two reactions: a hormone induced formation of the active adenylate cyclase-GTP complex, and a subsequent turn-off reaction in which hydrolysis of the bound nucleotide reverts the system to the inactive state. To test this model each of the two reactions was measured separately and their rate constants were used to estimate the steady state adenylate cyclase and GTPase activities. The first order rate constants were kon = 3 min-1 for the activation reaction and koff = 15 min-1 for the turn-off reaction. Substitution of these rate constants in the steady state equation of the regulatory cycle gave values of hormone stimulated adenylate cyclase and GTPase activities similar to those determined by direct measurements. Treatment of the adenylate cyclase with cholera toxin caused a decrease of 96% in the rate constant of the turn-off reaction. In this case too the activities calculated from the steady state equation were in good agreement with those determined directly."}
{"id": "PMID:203613", "title": "Dissociation of cyclic GMP from the negative inotropic action of carbachol in guinea pig atria.", "content": "The relationship between the negative inotropic action of carbachol and its ability to elevate cyclic GMP was determined in isolated paced guinea pig atria. A clear dissociation was observed between that concentration of carbachol which depressed contractility and that which elevated tissue cyclic GMP content. Doses as low as 0.03 micronM caused a negative inotropic effect while cyclic GMP was not elevated until concentrations nearly 100-fold higher were used. Thus a correlation between tissue cyclic GMP content and the negative inotropic action of carbachol was not found to exist in guinea pig atria.", "contents": "Dissociation of cyclic GMP from the negative inotropic action of carbachol in guinea pig atria. The relationship between the negative inotropic action of carbachol and its ability to elevate cyclic GMP was determined in isolated paced guinea pig atria. A clear dissociation was observed between that concentration of carbachol which depressed contractility and that which elevated tissue cyclic GMP content. Doses as low as 0.03 micronM caused a negative inotropic effect while cyclic GMP was not elevated until concentrations nearly 100-fold higher were used. Thus a correlation between tissue cyclic GMP content and the negative inotropic action of carbachol was not found to exist in guinea pig atria."}
{"id": "PMID:203614", "title": "Purification of a protein inhibitor of adenosine 3':5'-monophosphate-dependent protein kinase from bovine myocardium by a non-denaturing procedure.", "content": "The activities of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase may be partially controlled by a ubiquitous acidic heat-stable protein which inhibits the phosphotransferase reaction by interaction with the catalytic subunit of protein kinase (Walsh, D.A. et al. (1971), J. Biol. Chem. 246, 1977-1985). Since reported purification of this inhibitor involved subjecting tissue extracts to denaturing conditions, its existence under physiological conditions remained uncertain. A protein inhibitor, molecular weight 22,500, has been isolated from bovine myocardium by methods that do not include exposure to extreme heat or acid precipitation. The activity of this acidic protein is destroyed by exposure to trypsin and is unaffected by treatment with neuraminidase, RNAse or DNAse.", "contents": "Purification of a protein inhibitor of adenosine 3':5'-monophosphate-dependent protein kinase from bovine myocardium by a non-denaturing procedure. The activities of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase may be partially controlled by a ubiquitous acidic heat-stable protein which inhibits the phosphotransferase reaction by interaction with the catalytic subunit of protein kinase (Walsh, D.A. et al. (1971), J. Biol. Chem. 246, 1977-1985). Since reported purification of this inhibitor involved subjecting tissue extracts to denaturing conditions, its existence under physiological conditions remained uncertain. A protein inhibitor, molecular weight 22,500, has been isolated from bovine myocardium by methods that do not include exposure to extreme heat or acid precipitation. The activity of this acidic protein is destroyed by exposure to trypsin and is unaffected by treatment with neuraminidase, RNAse or DNAse."}
{"id": "PMID:203615", "title": "Inhibition of adenosine 3':5'-monophosphate-dependent protein kinase: comparison of a protein inhibitor with polyanions and substrate analogs.", "content": "The mechanism of inhibition of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase was studied using a protein inhibitor isolated by a non-denaturing procedure from bovine heart. This protein inhibitor interacts with the catalytic subunit of protein kinase and binds to some substrates of the kinase. Protein kinase activity can also be inhibited by polyanions which, like the protein inhibitor, bind to basic substrates but do not bind to the catalytic subunit of protein kinase. Peptides such as L-lysyl-L-tyrosyl-L-threonine that resemble the phosphate accepting site of protein kinase substrates competitively inhibit phosphorylation of histone. Protein kinase activity can thus be inhibited in vitro by interaction of the protein inhibitor with substrates, and/or the catalytic subunit of the kinase, by competition of substrate analogs with \"natural\" substrates and by direct interaction of polyanions with basic protein substrates for the phosphotransferase reaction.", "contents": "Inhibition of adenosine 3':5'-monophosphate-dependent protein kinase: comparison of a protein inhibitor with polyanions and substrate analogs. The mechanism of inhibition of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase was studied using a protein inhibitor isolated by a non-denaturing procedure from bovine heart. This protein inhibitor interacts with the catalytic subunit of protein kinase and binds to some substrates of the kinase. Protein kinase activity can also be inhibited by polyanions which, like the protein inhibitor, bind to basic substrates but do not bind to the catalytic subunit of protein kinase. Peptides such as L-lysyl-L-tyrosyl-L-threonine that resemble the phosphate accepting site of protein kinase substrates competitively inhibit phosphorylation of histone. Protein kinase activity can thus be inhibited in vitro by interaction of the protein inhibitor with substrates, and/or the catalytic subunit of the kinase, by competition of substrate analogs with \"natural\" substrates and by direct interaction of polyanions with basic protein substrates for the phosphotransferase reaction."}
{"id": "PMID:203616", "title": "Adrenergic desensitization in leukocytes of normal and asthmatic subjects.", "content": "Cyclic AMP was measured in leukocytes of normal and asthmatic subjects before and after one week of treatment with equal amounts of ephedrine. During the control and placebo periods, the measurements of cyclic AMP in leukocytes of asthmatic subjects were similar to those of normal individuals. After one week of treatment with ephedrine, both groups exhibited suppression of the leukocyte cyclic AMP response to adrenergic stimulation in vitro: however, the suppression of response was significantly greater in asthmatic subjects (p less than .u1). Subcutaneous administration of epinephrine was followed by further suppression of the leukocyte cyclic AMP response to in vitro stimulation which was similar in both groups during all treatment periods. The results indicate that in vivo exposure to adrenergic medications is followed by desensitization of the leukocyte responses to subsequent adrenergic stimulation in vitro. After administration of small doses of medication, the severity and/or duration of desensitization is significantly greater in asthmatic leukocytes.", "contents": "Adrenergic desensitization in leukocytes of normal and asthmatic subjects. Cyclic AMP was measured in leukocytes of normal and asthmatic subjects before and after one week of treatment with equal amounts of ephedrine. During the control and placebo periods, the measurements of cyclic AMP in leukocytes of asthmatic subjects were similar to those of normal individuals. After one week of treatment with ephedrine, both groups exhibited suppression of the leukocyte cyclic AMP response to adrenergic stimulation in vitro: however, the suppression of response was significantly greater in asthmatic subjects (p less than .u1). Subcutaneous administration of epinephrine was followed by further suppression of the leukocyte cyclic AMP response to in vitro stimulation which was similar in both groups during all treatment periods. The results indicate that in vivo exposure to adrenergic medications is followed by desensitization of the leukocyte responses to subsequent adrenergic stimulation in vitro. After administration of small doses of medication, the severity and/or duration of desensitization is significantly greater in asthmatic leukocytes."}
{"id": "PMID:203617", "title": "Dental and skeletal ages in hypopituitary patients.", "content": "Skeletal and dental ages were radiographically determined in 14 cases of confirmed growth hormone deficiency. The cases were in the 6.5- to 12-year-age group, and were receiving hormone therapy. Delay in skeletal age ranged from 24.8 to 32.3%, the average being 27.9%. There was very much less delay in dental age, ranging from only 4.3 to 19.7%; the average delay being approximately 9%. Most cases thus fell within normal limits. Seven patients had dental ages assessed before therapy and their dental age delays were comparable to those of the group as a whole. The four patients in the 12-year-old group showed a greater dental age delay then did the others. This could have been simply due to individual variation, or this delay could possibly support the view that dental development does become androgen dependent at puberty. None of the radiographs examined revealed any defects in dental development as has been reported elsewhere. While the small normal patient followed the general trend, the three low birth weight patients did not and it would not be instructive to measure the dental ages of larger numbers of these cases.", "contents": "Dental and skeletal ages in hypopituitary patients. Skeletal and dental ages were radiographically determined in 14 cases of confirmed growth hormone deficiency. The cases were in the 6.5- to 12-year-age group, and were receiving hormone therapy. Delay in skeletal age ranged from 24.8 to 32.3%, the average being 27.9%. There was very much less delay in dental age, ranging from only 4.3 to 19.7%; the average delay being approximately 9%. Most cases thus fell within normal limits. Seven patients had dental ages assessed before therapy and their dental age delays were comparable to those of the group as a whole. The four patients in the 12-year-old group showed a greater dental age delay then did the others. This could have been simply due to individual variation, or this delay could possibly support the view that dental development does become androgen dependent at puberty. None of the radiographs examined revealed any defects in dental development as has been reported elsewhere. While the small normal patient followed the general trend, the three low birth weight patients did not and it would not be instructive to measure the dental ages of larger numbers of these cases."}
{"id": "PMID:203619", "title": "Myocardial infarct imaging agents. III. Synthesis and evaluation of [203Hg] hydroxymercuriphthaleins.", "content": "Four Hg-203-mercurated phthaleins were prepared, purified, and compared with [203Hg] mercuric nitrate, [3H] phenolphthalein [203Hg] hydroxymercurifluorescein and Tc-99m-pyrophosphate in a rat model of myocardial necrosis to determine their specificities for damaged myocardium. The ratios of damaged myocardium to normal myocardium, and to blood, for the [203Hg] hydroxymercuriphthaleins (20.7-34.1 and 12.1-20.1, respectively) were somewhat lower than those reported previously for [203Hg] hydroxymercurifluorescein, but were higher than those found with [203Hg] mercuric nitrate, [3H] phenolphthalein, and Tc-99m pyrophosphate. Both the hydroxymercuri- functional group and the phthalein moiety are required for selectivity. The removal of the oxygen bridge present in fluorescein, and the replacement of carboxylic acid by sulfonic acid, had no significant effects on the sequestration process in damaged tissue.", "contents": "Myocardial infarct imaging agents. III. Synthesis and evaluation of [203Hg] hydroxymercuriphthaleins. Four Hg-203-mercurated phthaleins were prepared, purified, and compared with [203Hg] mercuric nitrate, [3H] phenolphthalein [203Hg] hydroxymercurifluorescein and Tc-99m-pyrophosphate in a rat model of myocardial necrosis to determine their specificities for damaged myocardium. The ratios of damaged myocardium to normal myocardium, and to blood, for the [203Hg] hydroxymercuriphthaleins (20.7-34.1 and 12.1-20.1, respectively) were somewhat lower than those reported previously for [203Hg] hydroxymercurifluorescein, but were higher than those found with [203Hg] mercuric nitrate, [3H] phenolphthalein, and Tc-99m pyrophosphate. Both the hydroxymercuri- functional group and the phthalein moiety are required for selectivity. The removal of the oxygen bridge present in fluorescein, and the replacement of carboxylic acid by sulfonic acid, had no significant effects on the sequestration process in damaged tissue."}
{"id": "PMID:203620", "title": "Metastasis of adenoid cystic carcinoma of the mandible to the Gasserian ganglion.", "content": "A case of adenoid cystic carcinoma of the mandible in a 47-year-old woman metastasized to the Gasserian ganglion probably through the perineural space of the inferior alveolar nerve. The patient was treated by irradiation after excision of the tumor from the ganglion. She is currently an outpatient in the oral and maxillofacial surgery department; two years and seven months after the first examination, there is no sign of recurrence or metastasis of adenoid cystic carcinoma.", "contents": "Metastasis of adenoid cystic carcinoma of the mandible to the Gasserian ganglion. A case of adenoid cystic carcinoma of the mandible in a 47-year-old woman metastasized to the Gasserian ganglion probably through the perineural space of the inferior alveolar nerve. The patient was treated by irradiation after excision of the tumor from the ganglion. She is currently an outpatient in the oral and maxillofacial surgery department; two years and seven months after the first examination, there is no sign of recurrence or metastasis of adenoid cystic carcinoma."}
{"id": "PMID:203621", "title": "Electroencephalographic sleep recordings and depression in the elderly.", "content": "Eighteen patients over the age of 60 who were experiencing a major depressive episode were studied on a Clinical Research Unit after they had been drug-free for at least two weeks. All-night electroencephalographic (EEG) recordings revealed considerable fragmentation of sleep, a mean sleep efficiency of 58 percent, and very little delta sleep. The findings of reduced sleep time, shortened REM latency, and high REM density were similar to those in depressed patients under the age of 60. These preliminary findings support the application of EEG sleep recordings as a tool for the differential diagnosis of depression in the elderly.", "contents": "Electroencephalographic sleep recordings and depression in the elderly. Eighteen patients over the age of 60 who were experiencing a major depressive episode were studied on a Clinical Research Unit after they had been drug-free for at least two weeks. All-night electroencephalographic (EEG) recordings revealed considerable fragmentation of sleep, a mean sleep efficiency of 58 percent, and very little delta sleep. The findings of reduced sleep time, shortened REM latency, and high REM density were similar to those in depressed patients under the age of 60. These preliminary findings support the application of EEG sleep recordings as a tool for the differential diagnosis of depression in the elderly."}
{"id": "PMID:203625", "title": "Adenylate kinase activity in various organs and tissues of mice with the obese-hyperglycemic syndrome (gene symbol Ob/Ob).", "content": "The activities of adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) in lyophilized cryostat sections of various organs from mice with the obese-hyperglycemic syndrome (gene symbol ob/ob) were measured fluorometrically. Skeletal and heart muscle tissues had the highest enzyme activities, i.e. 258 and 155 mmoles substrate converted per kg dry weight and per hr (MKH), respectively. Pancreatic islet specimens, which were composed mainly of B-cells, possessed the highest activitty of all parenchymatous cells studied, with 18 MKH as compared to 16 MKH for the cortical tubules of the kidney and 7 and 6 for the exocrine pancreas and liver cells, respectively. The granular layer of the cerebellum had enzyme activity of 31 MKH. The adenylate kinase activity in the B-cells was apparently not influenced by hyperglycemia since it was similar both in obese-hyperglycemic mice of different ages and in lean mice, although the blood sugar concentrations in such animals are much different.", "contents": "Adenylate kinase activity in various organs and tissues of mice with the obese-hyperglycemic syndrome (gene symbol Ob/Ob). The activities of adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) in lyophilized cryostat sections of various organs from mice with the obese-hyperglycemic syndrome (gene symbol ob/ob) were measured fluorometrically. Skeletal and heart muscle tissues had the highest enzyme activities, i.e. 258 and 155 mmoles substrate converted per kg dry weight and per hr (MKH), respectively. Pancreatic islet specimens, which were composed mainly of B-cells, possessed the highest activitty of all parenchymatous cells studied, with 18 MKH as compared to 16 MKH for the cortical tubules of the kidney and 7 and 6 for the exocrine pancreas and liver cells, respectively. The granular layer of the cerebellum had enzyme activity of 31 MKH. The adenylate kinase activity in the B-cells was apparently not influenced by hyperglycemia since it was similar both in obese-hyperglycemic mice of different ages and in lean mice, although the blood sugar concentrations in such animals are much different."}
{"id": "PMID:203626", "title": "In situ embedding method of cells grown in beem capsules for immunoelectron microscopic studies of oncornaviruses.", "content": "A technique of in situ embedding of cells grown in BEEM capsules has been devised for immunoelectron microscopic studies of oncornaviruses. As compared to other immunoelectron microscopic procedures, this technique is less time and reagent-consuming. The quality and specificity of this method were tested on well-characterized mouse mammary tumor virus (type B virus) and murine sarcoma virus (type C virus particles). This method gave good results in labeling of the virus particles with ferritin or peroxidase in the cells of mouse tissue cultures. In an application of this method, peroxidase labeling of type B virus particles was obtained in frozen sections of normal prostatic tissues of C3H/Dm and A/Dm strain mice treated with rabbit antiserum to mouse mammary tumor virus from A/Dm strain mouse milk. These results indicate that this method is useful and reliable for immunoelectron microscopy studies of oncornaviruses in tissue culture cells and also in frozen sections of tissues.", "contents": "In situ embedding method of cells grown in beem capsules for immunoelectron microscopic studies of oncornaviruses. A technique of in situ embedding of cells grown in BEEM capsules has been devised for immunoelectron microscopic studies of oncornaviruses. As compared to other immunoelectron microscopic procedures, this technique is less time and reagent-consuming. The quality and specificity of this method were tested on well-characterized mouse mammary tumor virus (type B virus) and murine sarcoma virus (type C virus particles). This method gave good results in labeling of the virus particles with ferritin or peroxidase in the cells of mouse tissue cultures. In an application of this method, peroxidase labeling of type B virus particles was obtained in frozen sections of normal prostatic tissues of C3H/Dm and A/Dm strain mice treated with rabbit antiserum to mouse mammary tumor virus from A/Dm strain mouse milk. These results indicate that this method is useful and reliable for immunoelectron microscopy studies of oncornaviruses in tissue culture cells and also in frozen sections of tissues."}
{"id": "PMID:203627", "title": "Passive protection of mice with the 19 S and 7 S fractions of anti-pertussis sera in experiment.", "content": "Protective activity of anti-persussis rabbit and mouse sera and 19 S and 7 S fractions obtained from these sera was investigated in the test of passive protection of mice on a model of pertussis meningoencephalitis. The method of simultaneous intracerebral administration of the serum or fraction with live culture of a virulent B. pertussis strain was used. Hyperimmune rabbit serum containing mercaptoethanol-resistant agglutinins in a high titre was found to have the most pronounced protective effect. Serum of mice, collected 14 days after single immunization of the animals, did not show any protective properties. A small amount of protective activity was observed in the serum collected on the 30th day after a single administration of the vaccine. A sharp increase in the protective activity of the serum was observed after double immunization of mice. Correlation was found between the increase in the titre of agglutinins (in particular of 7 S antibodies) and the protective activity of the serum. Protective properties of 19 S and 7 S fractions isolated from immune rabbit and mouse sera by the method of gel filtration were investigated. Both fractions were found to possess protective properties, but fraction 7 S was more active than fraction 19 S.", "contents": "Passive protection of mice with the 19 S and 7 S fractions of anti-pertussis sera in experiment. Protective activity of anti-persussis rabbit and mouse sera and 19 S and 7 S fractions obtained from these sera was investigated in the test of passive protection of mice on a model of pertussis meningoencephalitis. The method of simultaneous intracerebral administration of the serum or fraction with live culture of a virulent B. pertussis strain was used. Hyperimmune rabbit serum containing mercaptoethanol-resistant agglutinins in a high titre was found to have the most pronounced protective effect. Serum of mice, collected 14 days after single immunization of the animals, did not show any protective properties. A small amount of protective activity was observed in the serum collected on the 30th day after a single administration of the vaccine. A sharp increase in the protective activity of the serum was observed after double immunization of mice. Correlation was found between the increase in the titre of agglutinins (in particular of 7 S antibodies) and the protective activity of the serum. Protective properties of 19 S and 7 S fractions isolated from immune rabbit and mouse sera by the method of gel filtration were investigated. Both fractions were found to possess protective properties, but fraction 7 S was more active than fraction 19 S."}
{"id": "PMID:203628", "title": "Arboviruses in birds captured in Slovakia.", "content": "Virus neutralizing (VN) antibodies against Sindbis, tick-borne encephalitis (TBE), West Nile (WN), Tahyna and Calovo viruses were found in birds captured in Slovakia. In parallel, Sindbis, TBE and WN viruses were isolated from the blood, brain and liver of migrating birds.", "contents": "Arboviruses in birds captured in Slovakia. Virus neutralizing (VN) antibodies against Sindbis, tick-borne encephalitis (TBE), West Nile (WN), Tahyna and Calovo viruses were found in birds captured in Slovakia. In parallel, Sindbis, TBE and WN viruses were isolated from the blood, brain and liver of migrating birds."}
{"id": "PMID:203629", "title": "Spontaneous regression of Friend virus-induced erythroleukemia. III. The role of macrophages in regression.", "content": "The spontaneous regression of erythroleukemia induced by the RFV strain of Friend virus is a macrophage-dependent process. Functional suppression or elimination of the macrophage population in leukemic mice with silica, carrageenan, anti-macrophage serum, or trypan blue inhibited regression. Prior protection of the macrophages with PVNO allowed regression in silica or carrageenan-treated mice. Macrophage phagocytic activity was inhibited in about half the RFV-induced leukemic mice at 25 to 30 days post virus inoculation. Those animals with normal macrophages regressed, whereas whereas those with inhibited macrophages did not. Progressor mice could be induced to regress by inoculation with normal syngeneic macrophages; other cell types were ineffective. The inhibition of macrophage function in leukemic mice was the result of infection of the macrophages by virus. Removal of the infected cells by cytolysis with anti-virus antiserum and C restored the phagocytic activity of the population. Inhibited macrophages were less capable of responding to immobilized antigen-antibody complexes than normal macrophages, suggesting that the loss of function was due to a change in their Fc receptor.", "contents": "Spontaneous regression of Friend virus-induced erythroleukemia. III. The role of macrophages in regression. The spontaneous regression of erythroleukemia induced by the RFV strain of Friend virus is a macrophage-dependent process. Functional suppression or elimination of the macrophage population in leukemic mice with silica, carrageenan, anti-macrophage serum, or trypan blue inhibited regression. Prior protection of the macrophages with PVNO allowed regression in silica or carrageenan-treated mice. Macrophage phagocytic activity was inhibited in about half the RFV-induced leukemic mice at 25 to 30 days post virus inoculation. Those animals with normal macrophages regressed, whereas whereas those with inhibited macrophages did not. Progressor mice could be induced to regress by inoculation with normal syngeneic macrophages; other cell types were ineffective. The inhibition of macrophage function in leukemic mice was the result of infection of the macrophages by virus. Removal of the infected cells by cytolysis with anti-virus antiserum and C restored the phagocytic activity of the population. Inhibited macrophages were less capable of responding to immobilized antigen-antibody complexes than normal macrophages, suggesting that the loss of function was due to a change in their Fc receptor."}
{"id": "PMID:203630", "title": "Replication of herpes simplex virus and cytomegalovirus in human leukocytes.", "content": "Human peripheral blood leukocytes, lymphocyte subpopulations, and hemic cell lines were examined for their ability to supprot HSV and CMV replication. Mitogen-stimulated mononuclear leukocytes, B lymphocytes, and T lymphcytes supported the replication of HSV to high titers over 3 to 5 days of infection. HSV replicated in unstimulated mononuclear leukocyte cultures of one of five donors, and to a limited degree in untreated B lymphocytes of three of five donors; HSV replication was not detected in unstimulated T lymphocytes (five donors). There was no evidence of enhanced uptake of 3H-thymidine in the untreated donor cells that replicated HSV. CMV replication was not detected during 9 to 10 days of infection in untreated or mitogen-treated mononuclear leukocytes and lymphocyte subpopulations from the same adult donors or in neonatal cord blood leukocytes. The ability of the cells to support HSV or CMV replication did not correlate with the presence of specific antiviral antibodies in the donor serum. HSV replication in B, T, and myeloid cell lines to high titers over 5 days of infection, whereas CMV failed to replicate in any of the hemic cell lines. A persistent HSV infection has been established in a T cell line (CEM) with high titers of infectious virus being produced concurrently with growth of the cells over the first 11 weeks of infection.", "contents": "Replication of herpes simplex virus and cytomegalovirus in human leukocytes. Human peripheral blood leukocytes, lymphocyte subpopulations, and hemic cell lines were examined for their ability to supprot HSV and CMV replication. Mitogen-stimulated mononuclear leukocytes, B lymphocytes, and T lymphcytes supported the replication of HSV to high titers over 3 to 5 days of infection. HSV replicated in unstimulated mononuclear leukocyte cultures of one of five donors, and to a limited degree in untreated B lymphocytes of three of five donors; HSV replication was not detected in unstimulated T lymphocytes (five donors). There was no evidence of enhanced uptake of 3H-thymidine in the untreated donor cells that replicated HSV. CMV replication was not detected during 9 to 10 days of infection in untreated or mitogen-treated mononuclear leukocytes and lymphocyte subpopulations from the same adult donors or in neonatal cord blood leukocytes. The ability of the cells to support HSV or CMV replication did not correlate with the presence of specific antiviral antibodies in the donor serum. HSV replication in B, T, and myeloid cell lines to high titers over 5 days of infection, whereas CMV failed to replicate in any of the hemic cell lines. A persistent HSV infection has been established in a T cell line (CEM) with high titers of infectious virus being produced concurrently with growth of the cells over the first 11 weeks of infection."}
{"id": "PMID:203631", "title": "Specific lethality of silica for human peripheral blood mononuclear phagocytes, in vitro.", "content": "Human peripheral blood mononuclear cells, cultured in the presence of 100 microgram/ml protein-coated silica particles, were studied to determine changes in number and function of monocytes, immunoglobulin bearing (B), sheep red blood cell rosetting (T) lymphocytes and the effector cells of antibody dependent cell-mediated cytotoxicity (ADCC). After 24-48 h, phagocytic cells were effectively eliminated from culture but there was no significant reduction in number or function of T or B lymphocytes or in ADCC to cell line targets. ADCC to erythrocyte targets was inhibited but not completely blocked. It is concluded that silica is a specific toxin for human peripheral blood mononuclear phagocytes and may be useful in in vitro immunological studies as a means of eliminating or determining the role of these cells without resort to separation methods which result in losses of cells other than monocytes.", "contents": "Specific lethality of silica for human peripheral blood mononuclear phagocytes, in vitro. Human peripheral blood mononuclear cells, cultured in the presence of 100 microgram/ml protein-coated silica particles, were studied to determine changes in number and function of monocytes, immunoglobulin bearing (B), sheep red blood cell rosetting (T) lymphocytes and the effector cells of antibody dependent cell-mediated cytotoxicity (ADCC). After 24-48 h, phagocytic cells were effectively eliminated from culture but there was no significant reduction in number or function of T or B lymphocytes or in ADCC to cell line targets. ADCC to erythrocyte targets was inhibited but not completely blocked. It is concluded that silica is a specific toxin for human peripheral blood mononuclear phagocytes and may be useful in in vitro immunological studies as a means of eliminating or determining the role of these cells without resort to separation methods which result in losses of cells other than monocytes."}
{"id": "PMID:203632", "title": "A method using toluene-2,4-diisocyanate and glutaraldehyde to stabilize and conjugate antigens to erythrocytes for use in passive hemagglutination tests.", "content": "Erythrocytes were stabilized and activated for conjugation by simultaneous treatment with toluene-2,4-diisocyanate and glutaraldehyde. Following conjugation with an antigen, these cells were suitable for use in passive hemagglutination tests and could be stored in either hypo- or hyper-tonic solutions at 4 degrees C for at least 3 months without hemolysis or loss of agglutinating properties. Furthermore, these cells can be lyophilized and reconstituted with minimal loss of conjugation ability or of agglutination titer.", "contents": "A method using toluene-2,4-diisocyanate and glutaraldehyde to stabilize and conjugate antigens to erythrocytes for use in passive hemagglutination tests. Erythrocytes were stabilized and activated for conjugation by simultaneous treatment with toluene-2,4-diisocyanate and glutaraldehyde. Following conjugation with an antigen, these cells were suitable for use in passive hemagglutination tests and could be stored in either hypo- or hyper-tonic solutions at 4 degrees C for at least 3 months without hemolysis or loss of agglutinating properties. Furthermore, these cells can be lyophilized and reconstituted with minimal loss of conjugation ability or of agglutination titer."}
{"id": "PMID:203633", "title": "Preparation of sera for typing of adenovirus infections by immunofluorescence.", "content": "The conditions for preparation of adenovirus antisera with group, subgroup and type-specific reactivity to be used in the immunofluorescence technique have been evaluated. Group-specific antibodies were prepared by passing an antiserum against virions or hexons of one serotype through an immunosorbent column containing soluble viral components of an adenovirus type belonging to a different subgroup. The group-specific antibodies were recovered from the solid phase by elution at pH 2.8. Reagents specific for subgroup I and II were obtained by passing anti-dodecon sera through an immunosorbent column containing soluble viral components from heterologous subgroups. In this case antibodies not attaching to the absorbent were recovered. Sera against fibers of subgroup III members could be used as subgroupspecific sera without absorption. Type-specific antibodies were prepared by removal of antibodies of other specificities by passing anti-virion or anti-hexon sera through immunosorbent columns containing soluble viral components of an adenovirus type belonging to the same subgroup. Reagents specific for seven adenovirus types representing Rosen's three subgroups were prepared according to the outlined procedures.", "contents": "Preparation of sera for typing of adenovirus infections by immunofluorescence. The conditions for preparation of adenovirus antisera with group, subgroup and type-specific reactivity to be used in the immunofluorescence technique have been evaluated. Group-specific antibodies were prepared by passing an antiserum against virions or hexons of one serotype through an immunosorbent column containing soluble viral components of an adenovirus type belonging to a different subgroup. The group-specific antibodies were recovered from the solid phase by elution at pH 2.8. Reagents specific for subgroup I and II were obtained by passing anti-dodecon sera through an immunosorbent column containing soluble viral components from heterologous subgroups. In this case antibodies not attaching to the absorbent were recovered. Sera against fibers of subgroup III members could be used as subgroupspecific sera without absorption. Type-specific antibodies were prepared by removal of antibodies of other specificities by passing anti-virion or anti-hexon sera through immunosorbent columns containing soluble viral components of an adenovirus type belonging to the same subgroup. Reagents specific for seven adenovirus types representing Rosen's three subgroups were prepared according to the outlined procedures."}
{"id": "PMID:203634", "title": "The microbiological flora of penile ulcerations.", "content": "The penile ulcerations of 100 consecutive men were tested for microorganisms. A polymicrobial flora was identified in the ulcers of 97 men. The microorganisms recovered from these ulcers included combinations of anaerobic and aerobic bacteria (including Mycoplasma), herpes simplex virus, yeasts, and filamentous fungi. Fifty-three study entrants had microorganisms, identified by culture or serologic tests, that were considered primary in ulcer pathogenesis. Herpes simplex virus was the most prevalent and Treponema pallidum was the next most prevalent pathogen identified. Of our patients, 5% had two recognized pathogens confirmed by laboratory tests, and only one of these was suspected at clinical examination. In addition, the study suggests that microorganisms other than Haemophilus ducreyi can produce ulcers with a morphology mimicking chancroid.", "contents": "The microbiological flora of penile ulcerations. The penile ulcerations of 100 consecutive men were tested for microorganisms. A polymicrobial flora was identified in the ulcers of 97 men. The microorganisms recovered from these ulcers included combinations of anaerobic and aerobic bacteria (including Mycoplasma), herpes simplex virus, yeasts, and filamentous fungi. Fifty-three study entrants had microorganisms, identified by culture or serologic tests, that were considered primary in ulcer pathogenesis. Herpes simplex virus was the most prevalent and Treponema pallidum was the next most prevalent pathogen identified. Of our patients, 5% had two recognized pathogens confirmed by laboratory tests, and only one of these was suspected at clinical examination. In addition, the study suggests that microorganisms other than Haemophilus ducreyi can produce ulcers with a morphology mimicking chancroid."}
{"id": "PMID:203635", "title": "Effect of a polynucleotide interferon inducer of fungal origin on experimental rhinovirus infection in humans.", "content": "A double-stranded RNA of fungal origin (BRL 5907) was given intranasally to volunteers. Apart from mild local irritancy of the higher dosage, the compound was well tolerated. A double-blind placebo-controlled trial of a three-day course (5 mg per day) of BRL 5907 against challenge with rhinovirus type 4 showed that treatment was associated with a delay in onset of symptoms and a reduction in shedding of virus, but the differences were not statistically significant. Low titers of interferon were found in nasal washings.", "contents": "Effect of a polynucleotide interferon inducer of fungal origin on experimental rhinovirus infection in humans. A double-stranded RNA of fungal origin (BRL 5907) was given intranasally to volunteers. Apart from mild local irritancy of the higher dosage, the compound was well tolerated. A double-blind placebo-controlled trial of a three-day course (5 mg per day) of BRL 5907 against challenge with rhinovirus type 4 showed that treatment was associated with a delay in onset of symptoms and a reduction in shedding of virus, but the differences were not statistically significant. Low titers of interferon were found in nasal washings."}
{"id": "PMID:203636", "title": "Central nervous system immunity in mice infected with theiler's virus. I. Local neutralizing antibody response.", "content": "Experimental Theiler's mouse encephalomyelitis virus (TMEV) infection in mice is atypical of most other picornavirus infections because virus persists in the host. It was shown previously that low levels of infectious virus are readily detectable in the central nervous system (CNS) despite the presence of substantial titers of serum neutralizing antibody. In this study antibody assays were performed on CNS tissue homogenates, and neutralizing antibody was regularly found in the CNS of TMEV-infected mice. That neutralization by infected CNS extracts was due to antibody was demonstrated by the specificity of neutralization for TMEV and by elimination or marked reduction of neutralization by in vitro treatment with goat antiserum to mouse IgG. In addition, immunofluorescent staining consistently revealed IgG- but not IgM-containing cells in perivascular cuffs and parenchymal lesions of the brains of infected animals. Evidence of local antibody formation in the CNS was found in the actual reversal of the serum-CNS antibody ratio in about one-third of infected mice after three weeks. In contrast, normal mice had a mean serum-CNS antibody ratio of approximately 100:1 after passive transfer of antibody. Possible reasons for the fact that TMEV is not neutralized by antibody and chronic infection is not aborted include the formation of complexes of infectious virus and antibody in the CNS and the production of antibodies with low affinity for TMEV.", "contents": "Central nervous system immunity in mice infected with theiler's virus. I. Local neutralizing antibody response. Experimental Theiler's mouse encephalomyelitis virus (TMEV) infection in mice is atypical of most other picornavirus infections because virus persists in the host. It was shown previously that low levels of infectious virus are readily detectable in the central nervous system (CNS) despite the presence of substantial titers of serum neutralizing antibody. In this study antibody assays were performed on CNS tissue homogenates, and neutralizing antibody was regularly found in the CNS of TMEV-infected mice. That neutralization by infected CNS extracts was due to antibody was demonstrated by the specificity of neutralization for TMEV and by elimination or marked reduction of neutralization by in vitro treatment with goat antiserum to mouse IgG. In addition, immunofluorescent staining consistently revealed IgG- but not IgM-containing cells in perivascular cuffs and parenchymal lesions of the brains of infected animals. Evidence of local antibody formation in the CNS was found in the actual reversal of the serum-CNS antibody ratio in about one-third of infected mice after three weeks. In contrast, normal mice had a mean serum-CNS antibody ratio of approximately 100:1 after passive transfer of antibody. Possible reasons for the fact that TMEV is not neutralized by antibody and chronic infection is not aborted include the formation of complexes of infectious virus and antibody in the CNS and the production of antibodies with low affinity for TMEV."}
{"id": "PMID:203637", "title": "Persistent infection of a human lymphocyte cell line (Molt-4) with the kilham rat virus.", "content": "Inoculation of a human thymus-derived lymphocyte cell line (Molt-4) with the Kilham rat virus resulted in persistently infected cultures, that released infectious virus for periods up to seven months. At any time following infection, a small percentage of the cells were positive for rat virus antigens as determined by immunofluorescene assay.", "contents": "Persistent infection of a human lymphocyte cell line (Molt-4) with the kilham rat virus. Inoculation of a human thymus-derived lymphocyte cell line (Molt-4) with the Kilham rat virus resulted in persistently infected cultures, that released infectious virus for periods up to seven months. At any time following infection, a small percentage of the cells were positive for rat virus antigens as determined by immunofluorescene assay."}
{"id": "PMID:203641", "title": "Effects of adenosine and guanosine cyclic phosphates and their corresponding nucleotides and nucleosides on vitamin A-induced epidermal tumor promotion and growth in hamster cheek pouch.", "content": "Adenosine and guanosine cyclic monophosphates (cAMP and cGMP) exerted opposite effects at similar concentration and similar effects at markedly different concentrations on the yields of tumors promoted by vitamin A in hamster cheek pouch. Increasing the concentration of cAMP between 10(-5) M and 10(-3) M was associated with increases in tumor yield and diameter which partially or completely overcame the net tumor promotion inhibitory effects which were sometimes seen at 10(-5) M cAMP. In contrast, increasing the concentration of cGMP between 10(-5) M and 10(-3) M caused the net effects to change from increases to decreases in tumor yield without much change in diameter. The relative magnitudes of the tumor yield increasing and decreasing effects of the cyclic nucleotides varied substantially between experiments at constant concentration of cyclic nucleotide. Adenosine-5'-monophosphate (AMP) showed simultaneous tumor promotion inhibitory and growth stimulatory effects, the former effect being similar to that of cAMP but tumor yield decreased rather than increased as concentration of AMP was increased whereas the opposite occured with cAMP. Guanosine-5'-monophosphate (GMP) showed the tumor yield increasing effect of low concentraitons of cGMP but not the yield decreasing effect of high concentrations of cGMP. Adenosine (10(-3) M) showed a significant tumor yield increasing effect similar to that of 10(-3) M cAMP. Guanosine showed no significant effects at either 10(-3) M or 10(-5) M concentrations.", "contents": "Effects of adenosine and guanosine cyclic phosphates and their corresponding nucleotides and nucleosides on vitamin A-induced epidermal tumor promotion and growth in hamster cheek pouch. Adenosine and guanosine cyclic monophosphates (cAMP and cGMP) exerted opposite effects at similar concentration and similar effects at markedly different concentrations on the yields of tumors promoted by vitamin A in hamster cheek pouch. Increasing the concentration of cAMP between 10(-5) M and 10(-3) M was associated with increases in tumor yield and diameter which partially or completely overcame the net tumor promotion inhibitory effects which were sometimes seen at 10(-5) M cAMP. In contrast, increasing the concentration of cGMP between 10(-5) M and 10(-3) M caused the net effects to change from increases to decreases in tumor yield without much change in diameter. The relative magnitudes of the tumor yield increasing and decreasing effects of the cyclic nucleotides varied substantially between experiments at constant concentration of cyclic nucleotide. Adenosine-5'-monophosphate (AMP) showed simultaneous tumor promotion inhibitory and growth stimulatory effects, the former effect being similar to that of cAMP but tumor yield decreased rather than increased as concentration of AMP was increased whereas the opposite occured with cAMP. Guanosine-5'-monophosphate (GMP) showed the tumor yield increasing effect of low concentraitons of cGMP but not the yield decreasing effect of high concentrations of cGMP. Adenosine (10(-3) M) showed a significant tumor yield increasing effect similar to that of 10(-3) M cAMP. Guanosine showed no significant effects at either 10(-3) M or 10(-5) M concentrations."}
{"id": "PMID:203645", "title": "Effect of human chorionic gonadotrophin and ovine luteinizing hormone on rat ovarian macromolecular metabolism.", "content": "Administration of human chorionic gonadotrophin (HCG) or ovine LH to immature rats primed with pregnant mare serum gonadotrophin (PMSG) stimulated the rate of synthesis of polyadenylic acid (poly A)-rich RNA in the ovaries. The rate of total RNA synthesis was not affected significantly by hormone treatment, whereas protein synthesis was enhanced. The increase in the rate of synthesis of poly(A)-rich RNA in the ovaries could be inferred as induction of messenger RNA synthesis after the hormone treatment. The poly(A)-rich nature of the isolated RNA was established by oligo(dT)-cellulose chromatography, binding the Millipore filter disks and hydridization with [3H]polyuridylic acid. The level of cyclic AMP in the ovaries of such rats was also raised after administration of LH, the increase coincided with the increase in the rate of synthesis of poly(A)-rich RNA. The implications of these results are discussed in the light of the biochemical basis of luteinization and the action of LH.", "contents": "Effect of human chorionic gonadotrophin and ovine luteinizing hormone on rat ovarian macromolecular metabolism. Administration of human chorionic gonadotrophin (HCG) or ovine LH to immature rats primed with pregnant mare serum gonadotrophin (PMSG) stimulated the rate of synthesis of polyadenylic acid (poly A)-rich RNA in the ovaries. The rate of total RNA synthesis was not affected significantly by hormone treatment, whereas protein synthesis was enhanced. The increase in the rate of synthesis of poly(A)-rich RNA in the ovaries could be inferred as induction of messenger RNA synthesis after the hormone treatment. The poly(A)-rich nature of the isolated RNA was established by oligo(dT)-cellulose chromatography, binding the Millipore filter disks and hydridization with [3H]polyuridylic acid. The level of cyclic AMP in the ovaries of such rats was also raised after administration of LH, the increase coincided with the increase in the rate of synthesis of poly(A)-rich RNA. The implications of these results are discussed in the light of the biochemical basis of luteinization and the action of LH."}
{"id": "PMID:203648", "title": "Regulatory substances produced by lymphocytes. VI. Cell cycle specificity of inhibitor of DNA synthesis action in L cells.", "content": "IDS inhibits DNA synthesis and mitosis of L cells only when present during the late G1 phase of the cell cycle, as shown with L cells synchronized by a variety of methods. This corresponds well with earlier findings that IDS inhibits DNA synthesis in mitogen-stimulated lymphocytes when present between 16 and 24 h after adding mitogen. In both cell types, the inhibition produced by IDS appears to be totally the result of elevation of cAMP level. Thus, inhibitors of cAMP phosphodiesterase work synergistically with IDS, and activators of cAMP phosphodiesterase overcome the inhibition by IDS. This paper shows that IDS raises cAMP levels in L cells only within a narrow interval of the cell cycle, around 6-8 h after mitosis. This cell cycle specificity, which may be related to appearance of receptors for IDS only at discrete times, may be important in limiting IDS action to suppression, as elevated cAMP levels have a variety of other effects during other phases of the cell cycle.", "contents": "Regulatory substances produced by lymphocytes. VI. Cell cycle specificity of inhibitor of DNA synthesis action in L cells. IDS inhibits DNA synthesis and mitosis of L cells only when present during the late G1 phase of the cell cycle, as shown with L cells synchronized by a variety of methods. This corresponds well with earlier findings that IDS inhibits DNA synthesis in mitogen-stimulated lymphocytes when present between 16 and 24 h after adding mitogen. In both cell types, the inhibition produced by IDS appears to be totally the result of elevation of cAMP level. Thus, inhibitors of cAMP phosphodiesterase work synergistically with IDS, and activators of cAMP phosphodiesterase overcome the inhibition by IDS. This paper shows that IDS raises cAMP levels in L cells only within a narrow interval of the cell cycle, around 6-8 h after mitosis. This cell cycle specificity, which may be related to appearance of receptors for IDS only at discrete times, may be important in limiting IDS action to suppression, as elevated cAMP levels have a variety of other effects during other phases of the cell cycle."}
{"id": "PMID:203649", "title": "Bvr-1, a restriction locus of a type C RNA virus in the feline cellular genome: pleiotropic restriction of endogenous BALB virus in cat X mouse somatic cell hybrids.", "content": "Bvr-1 is a dominant X-linked feline gene which restricts the replication of B-tropic murineleukemia virus (B-MuLV) in somatic cell hybrids between murine BALB/c-RAG cells and FL-74 feline cells. Since the hybrids were originally derived by the hypoxanthine aminopterin thymidine selection scheme, counter selection experiments on 6-thioguanine result in preferential survival of hybrid cells which have spontaneously lost the feline X-chromosome on which is located the structural gene for hypoxanthine guanine phosphoribosyl transferase (IMP: pyrophosphate phosphoribosyl transferase, E.C. 2.4.2.8) and Bvr-1. Back selected Bvr-1- cells express high parental levels of B-MuLV. Bvr-1 effectively restricts the IdU-mediated induction of the endogenous xenotropic BALB virus (BALB: virus 2) but not the endogenous N-tropic virus (BALB: virus 1). Pleiotropic restriction of B-MuLV and X-MuLV, but not N-MuLV suggests that the viral targets of Bvr-1 (either viral components or functions in viral assembly) of the B-tropic and X-tropic endogenous BALB viruses are similar to each other but distinct from the target in the N-tropic virus. Very low levels of B-MuLV are detected in restricted cells, but this residual virus is not infectious in either NIH-3T3 or BALB-3T3 mouse cells which are genotypically Fv-1N/Fv-1N and Fv-1B/Fv-1B, respectively. Passage of residual virus through host cells without Fv-1 related restriction (SC-1) results in production of infectious B-MuLV indistinguishable from that produced by RAG parent cells.", "contents": "Bvr-1, a restriction locus of a type C RNA virus in the feline cellular genome: pleiotropic restriction of endogenous BALB virus in cat X mouse somatic cell hybrids. Bvr-1 is a dominant X-linked feline gene which restricts the replication of B-tropic murineleukemia virus (B-MuLV) in somatic cell hybrids between murine BALB/c-RAG cells and FL-74 feline cells. Since the hybrids were originally derived by the hypoxanthine aminopterin thymidine selection scheme, counter selection experiments on 6-thioguanine result in preferential survival of hybrid cells which have spontaneously lost the feline X-chromosome on which is located the structural gene for hypoxanthine guanine phosphoribosyl transferase (IMP: pyrophosphate phosphoribosyl transferase, E.C. 2.4.2.8) and Bvr-1. Back selected Bvr-1- cells express high parental levels of B-MuLV. Bvr-1 effectively restricts the IdU-mediated induction of the endogenous xenotropic BALB virus (BALB: virus 2) but not the endogenous N-tropic virus (BALB: virus 1). Pleiotropic restriction of B-MuLV and X-MuLV, but not N-MuLV suggests that the viral targets of Bvr-1 (either viral components or functions in viral assembly) of the B-tropic and X-tropic endogenous BALB viruses are similar to each other but distinct from the target in the N-tropic virus. Very low levels of B-MuLV are detected in restricted cells, but this residual virus is not infectious in either NIH-3T3 or BALB-3T3 mouse cells which are genotypically Fv-1N/Fv-1N and Fv-1B/Fv-1B, respectively. Passage of residual virus through host cells without Fv-1 related restriction (SC-1) results in production of infectious B-MuLV indistinguishable from that produced by RAG parent cells."}
{"id": "PMID:203650", "title": "Plasma membrane localization and metabolism of alkaline phosphodiesterase I in mouse peritoneal macrophages.", "content": "Alkaline phosphodiesterase I activity is demonstrable in lysates of mouse resident peritoneal macrophages (1.43 mU/mg), endotoxin-stimulated macrophages (1.36 mU/mg), and thioglycollate-stimulated macrophages (3.91 mU/mg), as well as in the lysates of several mouse cell lines. The enzyme showed little variation in culture, although serum deprivation caused a 50% decrease in enzyme activity. In each of the three macrophage types about 80% of the enzyme is inactivated by the diazonium salt of sulfanilic acid, indicating that this enzyme is a component of the plasma membrane. In thioglycollate-stimulated cells about the same fraction of enzyme can be inactivated with papain corroborating this assignment. The enzyme is inactivated with a half-time of 14.1 h in resident cells, but this is decreased to 8.2 h in endotoxin cells, and to 5.7 h in thioglycollate cells. These results are consistent with the hypothesis that the endogenous pinocytic rate is a major determinant of plasma membrane turnover. In addition, the different synthetic rates measured in resident and inflammatory cells support the concept that macrophage activation is a differentiative process leading to a qualitatively new cell type.", "contents": "Plasma membrane localization and metabolism of alkaline phosphodiesterase I in mouse peritoneal macrophages. Alkaline phosphodiesterase I activity is demonstrable in lysates of mouse resident peritoneal macrophages (1.43 mU/mg), endotoxin-stimulated macrophages (1.36 mU/mg), and thioglycollate-stimulated macrophages (3.91 mU/mg), as well as in the lysates of several mouse cell lines. The enzyme showed little variation in culture, although serum deprivation caused a 50% decrease in enzyme activity. In each of the three macrophage types about 80% of the enzyme is inactivated by the diazonium salt of sulfanilic acid, indicating that this enzyme is a component of the plasma membrane. In thioglycollate-stimulated cells about the same fraction of enzyme can be inactivated with papain corroborating this assignment. The enzyme is inactivated with a half-time of 14.1 h in resident cells, but this is decreased to 8.2 h in endotoxin cells, and to 5.7 h in thioglycollate cells. These results are consistent with the hypothesis that the endogenous pinocytic rate is a major determinant of plasma membrane turnover. In addition, the different synthetic rates measured in resident and inflammatory cells support the concept that macrophage activation is a differentiative process leading to a qualitatively new cell type."}
{"id": "PMID:203651", "title": "Human granulocyte generation of hydroxyl radical.", "content": "Human granulocytes were capable of oxidizing 2-keto-4 thiomethylbutyric acid to ethylene during phagocytosis or membrane perturbation. The reaction required hydrogen peroxide and superoxide and in addition was inhibited by various hydroxyl radical (OH) scavengers. These observations represent direct evidence for the generation of OH by human granulocytes. Further, inhibition of ethylene generation by azide and cyanide suggests that OH generation in granulocytes may be linked to myeloperoxidase.", "contents": "Human granulocyte generation of hydroxyl radical. Human granulocytes were capable of oxidizing 2-keto-4 thiomethylbutyric acid to ethylene during phagocytosis or membrane perturbation. The reaction required hydrogen peroxide and superoxide and in addition was inhibited by various hydroxyl radical (OH) scavengers. These observations represent direct evidence for the generation of OH by human granulocytes. Further, inhibition of ethylene generation by azide and cyanide suggests that OH generation in granulocytes may be linked to myeloperoxidase."}
{"id": "PMID:203652", "title": "Inborn resistance of mice to myxoviruses: macrophages express phenotype in vitro.", "content": "A strain of avian influenza A virus was adapted to grow in mouse peritoneal macrophages in vitro. The adapted strain, called M-TUR, induced a marked cytopathic effect in macrophages from susceptible mice. Mice homozygous (A2G) or heterozygous (F1 hybrids between A2G and several susceptible strains) for the gene Mx, shown previously to induce a high level of resistance towards lethal challenge by a number of myxoviruses in vivo, yielded peritoneal macrophages which were not affected by M-TUR. Peritoneal macrophages could be classified as resistant or susceptible to M-TUR without sacrificing the cell donor. Backcrosses were arranged between (A2G X A/J)F1 and A/J mice. 64 backcross animals could be tested individually both for resistance of their macrophages in vitro after challenge with M-TUR, and for resistance of the whole animal in vivo after challenge with NWS (a neurotropic variant of human influenza A virus). Macrophages from 36 backcross mice were classified as susceptible, and all of these mice died after challenge. Macrophages from 28 mice were classified as resistant, and 26 mice survived challenge. We conclude that resistance of macrophages and resistance of the whole animal are two facets of the same phenomenon.", "contents": "Inborn resistance of mice to myxoviruses: macrophages express phenotype in vitro. A strain of avian influenza A virus was adapted to grow in mouse peritoneal macrophages in vitro. The adapted strain, called M-TUR, induced a marked cytopathic effect in macrophages from susceptible mice. Mice homozygous (A2G) or heterozygous (F1 hybrids between A2G and several susceptible strains) for the gene Mx, shown previously to induce a high level of resistance towards lethal challenge by a number of myxoviruses in vivo, yielded peritoneal macrophages which were not affected by M-TUR. Peritoneal macrophages could be classified as resistant or susceptible to M-TUR without sacrificing the cell donor. Backcrosses were arranged between (A2G X A/J)F1 and A/J mice. 64 backcross animals could be tested individually both for resistance of their macrophages in vitro after challenge with M-TUR, and for resistance of the whole animal in vivo after challenge with NWS (a neurotropic variant of human influenza A virus). Macrophages from 36 backcross mice were classified as susceptible, and all of these mice died after challenge. Macrophages from 28 mice were classified as resistant, and 26 mice survived challenge. We conclude that resistance of macrophages and resistance of the whole animal are two facets of the same phenomenon."}
{"id": "PMID:203653", "title": "Properties of a transforming virus, KiMSV(RHHV), isolated from a co-culture of rat HTC-H1 cells with K-NRK cells.", "content": "Some morphological, biological, immunological and biochemical characterizations of a virus, rat helper virus pseudotype Kirsten sarcoma virus, KiMSV(RHHV), have been presented here. KiMSV(RHHV) has a type C virus ultrastructure. It is strictly rat tropic and is able to transform rat cells in vitro. The possibility of its being a xenotropic mouse virus has been carefully ruled out by exhaustive analyses of host range and immunological studies. Antigenically KiMSV(RHHV) demonstrates cross reactivity with an antiserum specific against rat leukaemia virus, no cross reactivity with antiserum against Moloney leukaemia virus, and only minor cross reactivity with antiserum against cat leukaemia virus. Analysis of virus proteins and glycoproteins by equilibrium acrylamide gradient gel electrophoresis showed that the virus complex possesses both a gp70 fraction and a p30 fraction. KiMSV(RHHV) sediments isopycnically in a linear sucrose gradient at 1.145 to 1.155 g/ml and possesses RNA and reverse transcriptase activity.", "contents": "Properties of a transforming virus, KiMSV(RHHV), isolated from a co-culture of rat HTC-H1 cells with K-NRK cells. Some morphological, biological, immunological and biochemical characterizations of a virus, rat helper virus pseudotype Kirsten sarcoma virus, KiMSV(RHHV), have been presented here. KiMSV(RHHV) has a type C virus ultrastructure. It is strictly rat tropic and is able to transform rat cells in vitro. The possibility of its being a xenotropic mouse virus has been carefully ruled out by exhaustive analyses of host range and immunological studies. Antigenically KiMSV(RHHV) demonstrates cross reactivity with an antiserum specific against rat leukaemia virus, no cross reactivity with antiserum against Moloney leukaemia virus, and only minor cross reactivity with antiserum against cat leukaemia virus. Analysis of virus proteins and glycoproteins by equilibrium acrylamide gradient gel electrophoresis showed that the virus complex possesses both a gp70 fraction and a p30 fraction. KiMSV(RHHV) sediments isopycnically in a linear sucrose gradient at 1.145 to 1.155 g/ml and possesses RNA and reverse transcriptase activity."}
{"id": "PMID:203654", "title": "The isolation of defective variants of simian virus 40 whose genomes contain sequences derived from adenovirus 2 DNA.", "content": "A new set of hybrid viruses has been isolated whose closed circular genomes 5 to 6 kB in size, contain DNA sequences derived in part from adenoviruses 2 and in part from SV40. The structure of these genomes is complex, but in the simplest case, analyses by restriction endonuclease digestion and hybridization indicate that the adenovirus 2 DNA is present as a continuous block, of maximum size 2.8 kB. Different hybrids contain sequences derived from different segments of the adenovirus 2 genome.", "contents": "The isolation of defective variants of simian virus 40 whose genomes contain sequences derived from adenovirus 2 DNA. A new set of hybrid viruses has been isolated whose closed circular genomes 5 to 6 kB in size, contain DNA sequences derived in part from adenoviruses 2 and in part from SV40. The structure of these genomes is complex, but in the simplest case, analyses by restriction endonuclease digestion and hybridization indicate that the adenovirus 2 DNA is present as a continuous block, of maximum size 2.8 kB. Different hybrids contain sequences derived from different segments of the adenovirus 2 genome."}
{"id": "PMID:203655", "title": "Tryptic peptide analysis of the structural proteins of vesicular stomatitis virus.", "content": "The individual structural polypeptides of vesicular stomatitis virus have been examined by tryptic peptide analysis of 35S-methionine preparations labelled in vivo and 125I-preparations labelled in vitro. Isolates of the two classical serotypes of the virus (Indiana and New Jersey) and of a sub-type of the Indiana serotype, Brazil virus, were compared. The study showed that the major internal proteins of all three viruses gave similar maps, whereas the surface glycoproteins gave distinct maps that had very few spots in common. The map of the glycoprotein of Brazil virus, which has been shown previously to be more closely related serologically to Indiana virus than to New Jersey virus, did not show any greater similarity to the Indiana virus than to the New Jersey virus glycoprotein. On the other hand, peptide maps of the nucleoprotein and matrix protein showed Indiana and Brazil viruses to be more closely related to each other than to New Jersey virus.", "contents": "Tryptic peptide analysis of the structural proteins of vesicular stomatitis virus. The individual structural polypeptides of vesicular stomatitis virus have been examined by tryptic peptide analysis of 35S-methionine preparations labelled in vivo and 125I-preparations labelled in vitro. Isolates of the two classical serotypes of the virus (Indiana and New Jersey) and of a sub-type of the Indiana serotype, Brazil virus, were compared. The study showed that the major internal proteins of all three viruses gave similar maps, whereas the surface glycoproteins gave distinct maps that had very few spots in common. The map of the glycoprotein of Brazil virus, which has been shown previously to be more closely related serologically to Indiana virus than to New Jersey virus, did not show any greater similarity to the Indiana virus than to the New Jersey virus glycoprotein. On the other hand, peptide maps of the nucleoprotein and matrix protein showed Indiana and Brazil viruses to be more closely related to each other than to New Jersey virus."}
{"id": "PMID:203656", "title": "Stable transformation of mouse, rabbit and monkey cells and abortive transformation of human cells by BK virus, a human papovavirus.", "content": "Semi-permissive mouse, rabbit and monkey cells were stably transformed by BK virus (BKV). The specificity of transformation was demonstrated by the presence of BKV tumour (T) antigen in nuclei of transformed cells and by virus rescue with Sendai virus-mediated fusion or transfection. Two out of seven BKV-transformed cell lines were oncogenic. Permissive human cells were only abortively transformed by BKV, since morphologically modified cells persisted in culture for a few passages and eventually died.", "contents": "Stable transformation of mouse, rabbit and monkey cells and abortive transformation of human cells by BK virus, a human papovavirus. Semi-permissive mouse, rabbit and monkey cells were stably transformed by BK virus (BKV). The specificity of transformation was demonstrated by the presence of BKV tumour (T) antigen in nuclei of transformed cells and by virus rescue with Sendai virus-mediated fusion or transfection. Two out of seven BKV-transformed cell lines were oncogenic. Permissive human cells were only abortively transformed by BKV, since morphologically modified cells persisted in culture for a few passages and eventually died."}
{"id": "PMID:203657", "title": "Observations on the growth and plaque assay of BK virus in cultured human and monkey cells.", "content": "Although human embryo kidney (HEK), muscle (HEM) and lung (HEL) cells are capable of supporting the replication of BK virus (BKV) through passage levels 9, 12 and 12 respectively, only third, fourth and fifth passage level HEK cells were found to be satisfactory for the plaque assay of the virus. BSC-I and VERO cells can also be used for the plaque assay of BKV. However, in HEK cells plaques can be visualized in 20 days (compared to 28 days in BSC-I cells), and since in VERO cells the plaques are poorly defined and the titre about I log10 lower than in either HEK or BSC-I cells, HEK cells were the ones chosen for use.", "contents": "Observations on the growth and plaque assay of BK virus in cultured human and monkey cells. Although human embryo kidney (HEK), muscle (HEM) and lung (HEL) cells are capable of supporting the replication of BK virus (BKV) through passage levels 9, 12 and 12 respectively, only third, fourth and fifth passage level HEK cells were found to be satisfactory for the plaque assay of the virus. BSC-I and VERO cells can also be used for the plaque assay of BKV. However, in HEK cells plaques can be visualized in 20 days (compared to 28 days in BSC-I cells), and since in VERO cells the plaques are poorly defined and the titre about I log10 lower than in either HEK or BSC-I cells, HEK cells were the ones chosen for use."}
{"id": "PMID:203664", "title": "Experimental lipid storage myopathy. A quantitative ultrastructural and biochemical study.", "content": "A lipid storage myopathy was induced in rats treated with daily doses of 2.5 g/kg brominated vegetable oil. As in human lipid storage myopathies, type I fibers were selectively severely affected, the lipid deposits were surrounded by mitochondria and the mitochondrial fraction of the affected fibers was increased. The oxidation of [U-14C]palmitate, [1(-14)C]octanoate and beta-[3(-14)C]hydroxybutyrate was significantly depressed but [1(-14)C]palmitate, as well as labeled pyruvate and succinate were oxidized at normal rates. The activities of long-chain, medium-chain and short-chain carnitine acyltransferases and the muscle carnitine levels were normal. The lipid storage is attributed to impaired beta oxidation of medium-chain and short-chain fatty acyl residues. An approach to the investigation of those human lipid storage myopathies not due to defects in the carnitine system is suggested.", "contents": "Experimental lipid storage myopathy. A quantitative ultrastructural and biochemical study. A lipid storage myopathy was induced in rats treated with daily doses of 2.5 g/kg brominated vegetable oil. As in human lipid storage myopathies, type I fibers were selectively severely affected, the lipid deposits were surrounded by mitochondria and the mitochondrial fraction of the affected fibers was increased. The oxidation of [U-14C]palmitate, [1(-14)C]octanoate and beta-[3(-14)C]hydroxybutyrate was significantly depressed but [1(-14)C]palmitate, as well as labeled pyruvate and succinate were oxidized at normal rates. The activities of long-chain, medium-chain and short-chain carnitine acyltransferases and the muscle carnitine levels were normal. The lipid storage is attributed to impaired beta oxidation of medium-chain and short-chain fatty acyl residues. An approach to the investigation of those human lipid storage myopathies not due to defects in the carnitine system is suggested."}
{"id": "PMID:203665", "title": "Clinical comparison of technetium-99m diphosphonate and pyrophosphate in bone scintigraphy: concise communication.", "content": "Thirty patients had bone scintigraphy with both Tc-99m pyrophosphate (Tc-PPi) and Tc-99m diphosphonate (Tc-HEDP). The images were given a composite rating for quality and the basis of three sets of criteria, and were also compared for the number of lesions detected by each agent. The two agents provided no difference in scan quality. Nevertheless, in ten of the 30 patients, at least two of the three readers detected with Tc-HEDP lesions that were not seen with Tc-PPi, and in two such cases all three readers considered the Tc-PPi scan normal. In another of these ten, two of three readers felt the Tc-PPi image was norm, whereas all three detected the lesion with Tc-HEDP. The reverse never occurred (P less than 0.01).", "contents": "Clinical comparison of technetium-99m diphosphonate and pyrophosphate in bone scintigraphy: concise communication. Thirty patients had bone scintigraphy with both Tc-99m pyrophosphate (Tc-PPi) and Tc-99m diphosphonate (Tc-HEDP). The images were given a composite rating for quality and the basis of three sets of criteria, and were also compared for the number of lesions detected by each agent. The two agents provided no difference in scan quality. Nevertheless, in ten of the 30 patients, at least two of the three readers detected with Tc-HEDP lesions that were not seen with Tc-PPi, and in two such cases all three readers considered the Tc-PPi scan normal. In another of these ten, two of three readers felt the Tc-PPi image was norm, whereas all three detected the lesion with Tc-HEDP. The reverse never occurred (P less than 0.01)."}
{"id": "PMID:203666", "title": "Radiometric detection of herpes simplex viruses.", "content": "Two radiometric techniques were investigated as possible means of detecting viruses in clinical specimens. The effect of herpes simplex virus on DNA synthesis by monolayers of human embryonic lung fibroblasts was monitored by the incorporation of [3H] thymidine or [125I] iododeoxyuridine ([125I] IdU). Radiometric results were compared with those obtained from visual examination for cytopathic effects in the same cell line. Cells infected with herpes simplex virus type-2 (HSV-2, 10(6.8) virions) showed a marked increase in [3H] thymidine incorporation 2--6 hr after infection. Types 1 and 2 herpes simplex virus yielded similar results, uith increased incorporation of tracer being observed 72 hr after infection with 10 virions. The [3H] thymidine technique was used successfully to assay mouse brains infected with HSV-1. Increased [125I] IdU incorporation was observed 6 hr after infection with 10(5)--10(6.8) HSV-1 virions, 24 hr after 10(4) virions, 48 hr after 10(3) virions, and 72 hr after 10--100 virions. The increased [125I] IdU incorporation was completely inhibited by preneutralization with immune serum. These radiometric techniques for detection of viral effect on cellular metabolism are simple, objective, and quantitative.", "contents": "Radiometric detection of herpes simplex viruses. Two radiometric techniques were investigated as possible means of detecting viruses in clinical specimens. The effect of herpes simplex virus on DNA synthesis by monolayers of human embryonic lung fibroblasts was monitored by the incorporation of [3H] thymidine or [125I] iododeoxyuridine ([125I] IdU). Radiometric results were compared with those obtained from visual examination for cytopathic effects in the same cell line. Cells infected with herpes simplex virus type-2 (HSV-2, 10(6.8) virions) showed a marked increase in [3H] thymidine incorporation 2--6 hr after infection. Types 1 and 2 herpes simplex virus yielded similar results, uith increased incorporation of tracer being observed 72 hr after infection with 10 virions. The [3H] thymidine technique was used successfully to assay mouse brains infected with HSV-1. Increased [125I] IdU incorporation was observed 6 hr after infection with 10(5)--10(6.8) HSV-1 virions, 24 hr after 10(4) virions, 48 hr after 10(3) virions, and 72 hr after 10--100 virions. The increased [125I] IdU incorporation was completely inhibited by preneutralization with immune serum. These radiometric techniques for detection of viral effect on cellular metabolism are simple, objective, and quantitative."}
{"id": "PMID:203667", "title": "Effect of cytomegalovirus infection on metabolism of WI-38 cell cultures: concise communication.", "content": "The effect of cytomegalovirus on the metabolism in monolayers of human embryonic lung fibroblasts (WI-38 cells) was studied. Effects of viral infection were examined by comparing [3H] thymidine incorporation in infected cells with that in uninfected cells. The time for detecting changes in cellular metabolism using the radiometric method was compared with that for observing cytopathic effects in infected cells. Compared with uninfected cells, cells infected with 10(4) TCID50 of virus showed nearly 400% increased in [3H] thymidine uptake 48 hr after infection. The radiometric method was able to detect 10(3) TCID50 of virus, with about 250% stimulation, 24--48 hr before visible signs of cytopathic effects. Our results suggest that with further development, radiometric measurement of metabolism in cytomegalovirus-infected cell cultures might provide a means of detecting viral presence in clinical assays. The radiometric method has the advantage of objectivity and potential for automation.", "contents": "Effect of cytomegalovirus infection on metabolism of WI-38 cell cultures: concise communication. The effect of cytomegalovirus on the metabolism in monolayers of human embryonic lung fibroblasts (WI-38 cells) was studied. Effects of viral infection were examined by comparing [3H] thymidine incorporation in infected cells with that in uninfected cells. The time for detecting changes in cellular metabolism using the radiometric method was compared with that for observing cytopathic effects in infected cells. Compared with uninfected cells, cells infected with 10(4) TCID50 of virus showed nearly 400% increased in [3H] thymidine uptake 48 hr after infection. The radiometric method was able to detect 10(3) TCID50 of virus, with about 250% stimulation, 24--48 hr before visible signs of cytopathic effects. Our results suggest that with further development, radiometric measurement of metabolism in cytomegalovirus-infected cell cultures might provide a means of detecting viral presence in clinical assays. The radiometric method has the advantage of objectivity and potential for automation."}
{"id": "PMID:203671", "title": "Side effects of diphenylhydantoin: a review.", "content": "For almost 40 years, diphenylhydantoin has been the preferred drug in the treatment of seizure disorders. Soon after the drug was introduced into clinical practice, gingival enlargement was noticed as a side effect and, despite much research effort, the etiology of this condition remains unknown. More recently, diphenylhydantoin-induced osteomalacia and the teratogenic effects of the drug have been reported. Recent advances in our knowledge of these conditions will be discussed and future directions for research will be outlined.", "contents": "Side effects of diphenylhydantoin: a review. For almost 40 years, diphenylhydantoin has been the preferred drug in the treatment of seizure disorders. Soon after the drug was introduced into clinical practice, gingival enlargement was noticed as a side effect and, despite much research effort, the etiology of this condition remains unknown. More recently, diphenylhydantoin-induced osteomalacia and the teratogenic effects of the drug have been reported. Recent advances in our knowledge of these conditions will be discussed and future directions for research will be outlined."}
{"id": "PMID:203672", "title": "A method for detecting therapeutic activity against Schistosoma mansoni in mice.", "content": "A simple and rapid assay, suitable for routine screening against Schistosoma mansoni in mice, can be achieved by using a reduction in the severity of hepatic lesions as the chief criterion of efficacy. Previous attempts to use this criterion were largely hampered by the use of inappropriate time schedules. Provided the timing of treatment and necropsy is restricted to a certain schedule, a mere glance at the opened abdomen of an infected mouse is sufficient to determine whether schistosome reproduction has been suppressed (by chemosterilization or by broader anthelmintic effects). The essence of the necessary schedule is treatment beginning at 4 weeks after infection and prolonged (continuously or intermittently) for 2 weeks, followed by necropsy at 8 weeks after infection. Using the methods described, two persons can easily examine mice for therapeutic response at the rate of 300 per hour. The assay has been shown to detect both schistosomaticidal and chemosterilizing compounds.", "contents": "A method for detecting therapeutic activity against Schistosoma mansoni in mice. A simple and rapid assay, suitable for routine screening against Schistosoma mansoni in mice, can be achieved by using a reduction in the severity of hepatic lesions as the chief criterion of efficacy. Previous attempts to use this criterion were largely hampered by the use of inappropriate time schedules. Provided the timing of treatment and necropsy is restricted to a certain schedule, a mere glance at the opened abdomen of an infected mouse is sufficient to determine whether schistosome reproduction has been suppressed (by chemosterilization or by broader anthelmintic effects). The essence of the necessary schedule is treatment beginning at 4 weeks after infection and prolonged (continuously or intermittently) for 2 weeks, followed by necropsy at 8 weeks after infection. Using the methods described, two persons can easily examine mice for therapeutic response at the rate of 300 per hour. The assay has been shown to detect both schistosomaticidal and chemosterilizing compounds."}
{"id": "PMID:203673", "title": "Release of endogenous serotonin from two identified serotonin-containing neurones and the physiological role of serotonin re-uptake.", "content": "1. The amounts of endogenous serotonin (5-HT) released into the medium by the cerebro-buccal ganglionic ring of Aplysia californica incubated in artificial sea water (ASW) were measured. The rate of spontaneous 5-HT release varied between 0.4 and 1.2 p-mole per hour, which is less than 1% of the total 5-HT present in this preparation.2. Direct stimulation of the ordinarily silent 5-HT-containing giant cerebral neurones resulted in a 80-100% increase of the 5-HT released, but only when the 5-HT uptake was blocked by chlorimipramine (1-10 muM).3. High K(+) media (50 mM) also caused a significant increase in the amount of 5-HT released from the preparation provided that chlorimipramine (1-10 muM) was present in the incubation fluid.4. Co(2+) ions (10-30 mM) added to the incubating medium blocked the spontaneous leak of endogenous 5-HT as well as the release, in the presence of chlorimipramine, evoked either by stimulation of the 5-HT-giant cerebral neurones or high K(+)-media.5. In the presence of chlorimipramine or desmethylimipramine, the duration and/or the amplitude of the excitatory or the inhibitory synaptic potentials evoked in the buccal neurones by the stimulation of the 5-HT giant cerebral neurones were markedly enhanced.6. These results strongly support the idea that 5-HT is the synaptic transmitter released at the excitatory and inhibitory junctions established by the 5-HT giant cerebral neurones in the ipsilateral buccal ganglia. In addition, they underline the role of amine re-uptake in the physiological inactivation of 5-HT as a transmitter.", "contents": "Release of endogenous serotonin from two identified serotonin-containing neurones and the physiological role of serotonin re-uptake. 1. The amounts of endogenous serotonin (5-HT) released into the medium by the cerebro-buccal ganglionic ring of Aplysia californica incubated in artificial sea water (ASW) were measured. The rate of spontaneous 5-HT release varied between 0.4 and 1.2 p-mole per hour, which is less than 1% of the total 5-HT present in this preparation.2. Direct stimulation of the ordinarily silent 5-HT-containing giant cerebral neurones resulted in a 80-100% increase of the 5-HT released, but only when the 5-HT uptake was blocked by chlorimipramine (1-10 muM).3. High K(+) media (50 mM) also caused a significant increase in the amount of 5-HT released from the preparation provided that chlorimipramine (1-10 muM) was present in the incubation fluid.4. Co(2+) ions (10-30 mM) added to the incubating medium blocked the spontaneous leak of endogenous 5-HT as well as the release, in the presence of chlorimipramine, evoked either by stimulation of the 5-HT-giant cerebral neurones or high K(+)-media.5. In the presence of chlorimipramine or desmethylimipramine, the duration and/or the amplitude of the excitatory or the inhibitory synaptic potentials evoked in the buccal neurones by the stimulation of the 5-HT giant cerebral neurones were markedly enhanced.6. These results strongly support the idea that 5-HT is the synaptic transmitter released at the excitatory and inhibitory junctions established by the 5-HT giant cerebral neurones in the ipsilateral buccal ganglia. In addition, they underline the role of amine re-uptake in the physiological inactivation of 5-HT as a transmitter."}
{"id": "PMID:203674", "title": "Octanol reduces end-plate channel lifetime.", "content": "1. Post-synaptic effects of n-octanol at concentrations of 0.1-1 mM were examined in toad sartorius muscles by use of extracellular and voltage-clamp techniques.2. Octanol depressed the amplitude and duration of miniature end-plate currents and hence depressed neuromuscular transmission.3. The decay of miniature end-plate currents remained exponential in octanol solutions even when the time constant of decay (tau(D)) was decreased by 80-90%.4. The lifetime of end-plate channels, obtained by analysis of acetylcholine noise, was also decreased by octanol. The average lifetime measured from noise spectra agreed reasonably well with the time constant of decay of miniature end-plate currents, both in control solution and in octanol solutions.5. Octanol caused a reduction in the conductance of end-plate channels. Single channel conductance was on average about 25 pS in control solution and 20 pS in octanol.6. In most cells the normal voltage sensitivity of the decay of miniature end-plate currents was retained in octanol solutions. The lifetime of end-plate channels measured from acetylcholine noise also remained voltage-sensitive in octanol solutions. In some experiments in which channel lifetime was exceptionally reduced the voltage sensitivity was less than normal.7. In octanol solutions, tau(D) was still very sensitive to temperature changes in most cells although in some the temperature sensitivity of tau(D) was clearly reduced. Changes in tau(D) with temperature could generally be fitted by the Arrhenius equation suggesting that a single step reaction controlled the decay of currents both in control and in octanol solutions. In some cells in which tau(D) became less than 0.3 ms, the relationship between tau(D) and temperature became inconsistent with the Arrhenius equation.8. As the decay of end-plate currents in octanol solutions remains exponential, and the voltage and temperature sensitivity can be unchanged even when tau(D) is significantly reduced, it seems likely that octanol decreases tau(D) by increasing the rate of the reaction which normally controls the lifetime of end-plate channels.", "contents": "Octanol reduces end-plate channel lifetime. 1. Post-synaptic effects of n-octanol at concentrations of 0.1-1 mM were examined in toad sartorius muscles by use of extracellular and voltage-clamp techniques.2. Octanol depressed the amplitude and duration of miniature end-plate currents and hence depressed neuromuscular transmission.3. The decay of miniature end-plate currents remained exponential in octanol solutions even when the time constant of decay (tau(D)) was decreased by 80-90%.4. The lifetime of end-plate channels, obtained by analysis of acetylcholine noise, was also decreased by octanol. The average lifetime measured from noise spectra agreed reasonably well with the time constant of decay of miniature end-plate currents, both in control solution and in octanol solutions.5. Octanol caused a reduction in the conductance of end-plate channels. Single channel conductance was on average about 25 pS in control solution and 20 pS in octanol.6. In most cells the normal voltage sensitivity of the decay of miniature end-plate currents was retained in octanol solutions. The lifetime of end-plate channels measured from acetylcholine noise also remained voltage-sensitive in octanol solutions. In some experiments in which channel lifetime was exceptionally reduced the voltage sensitivity was less than normal.7. In octanol solutions, tau(D) was still very sensitive to temperature changes in most cells although in some the temperature sensitivity of tau(D) was clearly reduced. Changes in tau(D) with temperature could generally be fitted by the Arrhenius equation suggesting that a single step reaction controlled the decay of currents both in control and in octanol solutions. In some cells in which tau(D) became less than 0.3 ms, the relationship between tau(D) and temperature became inconsistent with the Arrhenius equation.8. As the decay of end-plate currents in octanol solutions remains exponential, and the voltage and temperature sensitivity can be unchanged even when tau(D) is significantly reduced, it seems likely that octanol decreases tau(D) by increasing the rate of the reaction which normally controls the lifetime of end-plate channels."}
{"id": "PMID:203675", "title": "Formation and elimination of foreign synapses on adult salamander muscle.", "content": "1. Synapses by flexor nerve were induced on denervated extensor muscle in adult salamander forelimbs. Excitatory potentials evoked by these ;foreign' synapses were at first small but increased to normal amplitude within several weeks, in the absence of correct nerve reinnervation.2. Upon return of the correct nerve the efficacy of foreign synaptic transmission began to decline. The time of initiation of this decline correlated well with the resumption of correct nerve transmission. The suppression of foreign transmission involved a reduction in mean quantal content of transmitter release.3. Suppression of foreign synapses was sufficiently thorough that most ceased transmitting entirely. Before reinnervation by the correct nerve 97% of the extensor muscle fibres received functional foreign synapses while 4-6 months after correct nerve return only 35% of the fibres retained foreign synapses, with weak transmission.4. Two lines of evidence indicate that suppressed foreign synapses are lost from the muscle: (a) a second correct nerve lesion 6-8 months after the initial denervation produced no significant increase in the proportion of fibres with foreign transmission and (b) four muscles which showed complete suppression of foreign transmission were bathed in medium containing horseradish peroxidase (h.r.p.) and the correct nerve was stimulated repetitively. Subsequent histochemical staining for h.r.p. and examination of synapses by electron microscopy revealed that 94% of the axon terminals had h.r.p. incorporated in vesicles. Thus at least that percentage of all identifiable synapses were from the correct nerve.5. This ability to eliminate incorrect synapses in favour of correct ones is speculated to be a general characteristic of embryonic nervous systems, which in adulthood is retained by salamanders but lost by most other animals.", "contents": "Formation and elimination of foreign synapses on adult salamander muscle. 1. Synapses by flexor nerve were induced on denervated extensor muscle in adult salamander forelimbs. Excitatory potentials evoked by these ;foreign' synapses were at first small but increased to normal amplitude within several weeks, in the absence of correct nerve reinnervation.2. Upon return of the correct nerve the efficacy of foreign synaptic transmission began to decline. The time of initiation of this decline correlated well with the resumption of correct nerve transmission. The suppression of foreign transmission involved a reduction in mean quantal content of transmitter release.3. Suppression of foreign synapses was sufficiently thorough that most ceased transmitting entirely. Before reinnervation by the correct nerve 97% of the extensor muscle fibres received functional foreign synapses while 4-6 months after correct nerve return only 35% of the fibres retained foreign synapses, with weak transmission.4. Two lines of evidence indicate that suppressed foreign synapses are lost from the muscle: (a) a second correct nerve lesion 6-8 months after the initial denervation produced no significant increase in the proportion of fibres with foreign transmission and (b) four muscles which showed complete suppression of foreign transmission were bathed in medium containing horseradish peroxidase (h.r.p.) and the correct nerve was stimulated repetitively. Subsequent histochemical staining for h.r.p. and examination of synapses by electron microscopy revealed that 94% of the axon terminals had h.r.p. incorporated in vesicles. Thus at least that percentage of all identifiable synapses were from the correct nerve.5. This ability to eliminate incorrect synapses in favour of correct ones is speculated to be a general characteristic of embryonic nervous systems, which in adulthood is retained by salamanders but lost by most other animals."}
{"id": "PMID:203676", "title": "The control of enzyme secretion from fly salivary glands.", "content": "1. Stimulation of fluid secretion from fly salivary glands by 5-hydroxytryptamine (5-HT) is known to involve calcium and cyclic AMP. Isolated salivary glands were used to investigate the role of these second messengers in the control of enzyme (sucrase) secretion.2. The protein component of secretion from isolated glands treated with 5-HT appears to be identical to that of saliva secreted by flies during feeding.3. Stimulation of fluid secretion by 5-HT follows a definite dose-response curve, but there is no consistent relationship between the rate of enzyme secretion and the stimulating concentration of 5-HT.4. Exogenous cyclic AMP causes secretion of enzymes as well as of fluid, thus mimicking the action of 5-HT. The phosphodiesterase inhibitor theophylline enhances the rate of 5-HT-stimulated enzyme secretion.5. Removal of calcium from the bathing medium enhances enzyme secretion in response to 5 or 10 nM-5-HT but has no effect on enzyme secretion stimulated by 100 nM-5-HT or by cyclic AMP.6. Addition of 0.1 mM-lanthanum to medium containing 2 mM-calcium mimics the effect of calcium-free solution on 5-HT-stimulated enzyme secretion.7. The ionophore A 23187 causes secretion of both fluid and enzyme. The secretory rate is initially high but soon declines and ceases after about 40 min.8. Enzyme secretion in response to 5-HT or to cyclic AMP is progressively inhibited as the concentration of potassium is increased from 10 to 80 mM. Secretion in response to A 23187 is initially inhibited by 80 mM-potassium but then partially recovers.9. The rate of enzyme secretion appears to be affected by the intracellular concentrations of both calcium and cyclic AMP. It is possible that the rate of enzyme secretion increases as the intracellular calcium concentration rises, until the optimal calcium concentration is reached when further increase in the level of calcium progressively inhibits secretion. The optimal calcium concentration for enzyme secretion is lower than that for fluid secretion, and 5-HT normally causes maximal fluid secretion and submaximal enzyme secretion.", "contents": "The control of enzyme secretion from fly salivary glands. 1. Stimulation of fluid secretion from fly salivary glands by 5-hydroxytryptamine (5-HT) is known to involve calcium and cyclic AMP. Isolated salivary glands were used to investigate the role of these second messengers in the control of enzyme (sucrase) secretion.2. The protein component of secretion from isolated glands treated with 5-HT appears to be identical to that of saliva secreted by flies during feeding.3. Stimulation of fluid secretion by 5-HT follows a definite dose-response curve, but there is no consistent relationship between the rate of enzyme secretion and the stimulating concentration of 5-HT.4. Exogenous cyclic AMP causes secretion of enzymes as well as of fluid, thus mimicking the action of 5-HT. The phosphodiesterase inhibitor theophylline enhances the rate of 5-HT-stimulated enzyme secretion.5. Removal of calcium from the bathing medium enhances enzyme secretion in response to 5 or 10 nM-5-HT but has no effect on enzyme secretion stimulated by 100 nM-5-HT or by cyclic AMP.6. Addition of 0.1 mM-lanthanum to medium containing 2 mM-calcium mimics the effect of calcium-free solution on 5-HT-stimulated enzyme secretion.7. The ionophore A 23187 causes secretion of both fluid and enzyme. The secretory rate is initially high but soon declines and ceases after about 40 min.8. Enzyme secretion in response to 5-HT or to cyclic AMP is progressively inhibited as the concentration of potassium is increased from 10 to 80 mM. Secretion in response to A 23187 is initially inhibited by 80 mM-potassium but then partially recovers.9. The rate of enzyme secretion appears to be affected by the intracellular concentrations of both calcium and cyclic AMP. It is possible that the rate of enzyme secretion increases as the intracellular calcium concentration rises, until the optimal calcium concentration is reached when further increase in the level of calcium progressively inhibits secretion. The optimal calcium concentration for enzyme secretion is lower than that for fluid secretion, and 5-HT normally causes maximal fluid secretion and submaximal enzyme secretion."}
{"id": "PMID:203677", "title": "The effect of age on neuromuscular transmission.", "content": "1. Resting membrane potentials (RMPs), spontaneous miniature end-plate potentials (m.e.p.p.s), and evoked end-plate potentials (e.p.p.s) were recorded in phrenic nerve-hemidiaphragm preparations from rats at ages from 11 to 375 days. 2. The mean RMP increased from -64.1 +/- 1.2 mV (mean +/- S.E.) at age 11 days to -71.3 +/- 1.0 mV at age 30 days, after which there was no significant change with age. 3. The mean amplitude of m.e.p.p.s decreased from 1.088 +/- 0.070 mV at 11 days of age to 0.405 +/- 0.030 mV at 175 days of age, after which there was no significant change. 4. There was a rpaid, large increase in the frequency of m.e.p.p.s from 0.02/sec to 0.97/sec (geometric means) between 11 and 23 days of age, followed by a slower increase to 3.19/sec at 175 days of age. Subsequently there was a decrease by 2.58/sec at 375 days of age. 5. The mean of quantum content of plateau e.p.p.s elicited at a frequency of 10 Hz increased from 20.5 quanta/e.p.p. to 169.9 quanta/e.p.p. (geometric means) between 11 and 175 days of age and then decreased to 120.4 quanta/e.p.p. at 375 days of age. 6. The mean quantum content of the first e.p.p.s of trains of e.p.p.s increased from 44.2 quanta/e.p.p. to 468.8 quanta/e.p.p. (geometric means) between 11 and 175 days of age and then decreased to 358.1 quanta/e.p.p. at 375 days of age. 7. The calculated safety factor of neuromuscular transmission increased with age up to 110-175 days and subsequently decreased. 8. The change in all the above parameters occurred most rapidly in the first 6 weeks of life. The rapidity of these changes indicates that great care must be taken to ensure that control and experimental animals are adequately matched according to age, especially when rats weighing less than about 300 g are used.", "contents": "The effect of age on neuromuscular transmission. 1. Resting membrane potentials (RMPs), spontaneous miniature end-plate potentials (m.e.p.p.s), and evoked end-plate potentials (e.p.p.s) were recorded in phrenic nerve-hemidiaphragm preparations from rats at ages from 11 to 375 days. 2. The mean RMP increased from -64.1 +/- 1.2 mV (mean +/- S.E.) at age 11 days to -71.3 +/- 1.0 mV at age 30 days, after which there was no significant change with age. 3. The mean amplitude of m.e.p.p.s decreased from 1.088 +/- 0.070 mV at 11 days of age to 0.405 +/- 0.030 mV at 175 days of age, after which there was no significant change. 4. There was a rpaid, large increase in the frequency of m.e.p.p.s from 0.02/sec to 0.97/sec (geometric means) between 11 and 23 days of age, followed by a slower increase to 3.19/sec at 175 days of age. Subsequently there was a decrease by 2.58/sec at 375 days of age. 5. The mean of quantum content of plateau e.p.p.s elicited at a frequency of 10 Hz increased from 20.5 quanta/e.p.p. to 169.9 quanta/e.p.p. (geometric means) between 11 and 175 days of age and then decreased to 120.4 quanta/e.p.p. at 375 days of age. 6. The mean quantum content of the first e.p.p.s of trains of e.p.p.s increased from 44.2 quanta/e.p.p. to 468.8 quanta/e.p.p. (geometric means) between 11 and 175 days of age and then decreased to 358.1 quanta/e.p.p. at 375 days of age. 7. The calculated safety factor of neuromuscular transmission increased with age up to 110-175 days and subsequently decreased. 8. The change in all the above parameters occurred most rapidly in the first 6 weeks of life. The rapidity of these changes indicates that great care must be taken to ensure that control and experimental animals are adequately matched according to age, especially when rats weighing less than about 300 g are used."}
{"id": "PMID:203694", "title": "Bisamidines of 2,6-diaminoanthraquinone as antiamebic agents.", "content": "A series of bisamidines of 2,6-diaminoanthraquinone was synthesized and tested against cecal and hepatic forms of Entamoeba histolytica infections in rats and hamsters, respectively. A number of compounds were found to have good activity against infections in both species.", "contents": "Bisamidines of 2,6-diaminoanthraquinone as antiamebic agents. A series of bisamidines of 2,6-diaminoanthraquinone was synthesized and tested against cecal and hepatic forms of Entamoeba histolytica infections in rats and hamsters, respectively. A number of compounds were found to have good activity against infections in both species."}
{"id": "PMID:203695", "title": "Chemical analysis of an angiofibroma from a patient with tuberous sclerosis.", "content": "Amino-acid analyses on the acid hydrolysates of an angiofibroma and skin established that the former tissue contained less collagen than skin based on the reduced content of hydroxyproline, glycine, proline and alanine in the tumour. From lysosomal enzyme measurements it became evident that the specific activities of the hexosaminidases, beta-glucuronidase and beta-galactosidase were elevated. Analyses of the alcohol insoluble fraction following pronase digestion revealed that the tumour contained more acidic glycosaminoglycan (AG) than skin as assessed by uronic acid and hexosamine measurements. More outstanding, however, was the seven-fold increase in the total carbohydrate in the AG fraction of the tumour. The overall composition of this fraction was very similar to comparable material from foetal skin except that the tumour fraction contained increased sulphate concentration.", "contents": "Chemical analysis of an angiofibroma from a patient with tuberous sclerosis. Amino-acid analyses on the acid hydrolysates of an angiofibroma and skin established that the former tissue contained less collagen than skin based on the reduced content of hydroxyproline, glycine, proline and alanine in the tumour. From lysosomal enzyme measurements it became evident that the specific activities of the hexosaminidases, beta-glucuronidase and beta-galactosidase were elevated. Analyses of the alcohol insoluble fraction following pronase digestion revealed that the tumour contained more acidic glycosaminoglycan (AG) than skin as assessed by uronic acid and hexosamine measurements. More outstanding, however, was the seven-fold increase in the total carbohydrate in the AG fraction of the tumour. The overall composition of this fraction was very similar to comparable material from foetal skin except that the tumour fraction contained increased sulphate concentration."}
{"id": "PMID:203700", "title": "Transformation in vitro of glial hamster cells by Rous sarcoma virus.", "content": "Cell lines from the brains of inbred CF hamster embryos were established in vitro. The morphology of the cells in the light and electron microscopes was that of glial cells, and the cells contained the nervous system-specific protein S-100. Infection with the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup B, resulted in foci of transformation. The transformed cells were virogenic and upon intracerebral and sc inoculations into young hamsters, they developed into histologically typical gliomas.", "contents": "Transformation in vitro of glial hamster cells by Rous sarcoma virus. Cell lines from the brains of inbred CF hamster embryos were established in vitro. The morphology of the cells in the light and electron microscopes was that of glial cells, and the cells contained the nervous system-specific protein S-100. Infection with the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup B, resulted in foci of transformation. The transformed cells were virogenic and upon intracerebral and sc inoculations into young hamsters, they developed into histologically typical gliomas."}
{"id": "PMID:203703", "title": "Suppressor cells in mice with murine mammary tumor virus-induced mammary tumors. I. Inhibition of mitogen-induced lymphocyte stimulation.", "content": "Suppressor cell activity was present in the glass-adherent fraction of spleen cells from C3H mice bearing murine mammary tumor virus-induced mammary tumors. These cells effectively suppressed the blastogenic response of syngeneic normal lymphocytes to concanavalin A (Con A). Suppression by the spleen cells from mammary tumor-bearing mice was not dependent on DNA synthesis. Removal of the suppressor cells from spleen cell suspensions of tumor-bearing mice was not dependent on DNA synthesis. Removal of the suppressor cells from spleen cell suspensions of tumor-bearing animals (TBA) by passage of the cells on glass wool columns increased the Con A response of the remaining cells by fourfold to eightfold. Characterization of the suppressor population indicated that the cells were also adherent to nylon wool but not to plastic and contained a significantly increased proportion of surface immunoglobulin-bearing and complement receptor-bearing lymphocytes. Depletion of macrophages and T-cells did not remove the suppressive activity from the spleens of the TBA. The results were consistent with the identification of the suppressor cell as a B-cell.", "contents": "Suppressor cells in mice with murine mammary tumor virus-induced mammary tumors. I. Inhibition of mitogen-induced lymphocyte stimulation. Suppressor cell activity was present in the glass-adherent fraction of spleen cells from C3H mice bearing murine mammary tumor virus-induced mammary tumors. These cells effectively suppressed the blastogenic response of syngeneic normal lymphocytes to concanavalin A (Con A). Suppression by the spleen cells from mammary tumor-bearing mice was not dependent on DNA synthesis. Removal of the suppressor cells from spleen cell suspensions of tumor-bearing mice was not dependent on DNA synthesis. Removal of the suppressor cells from spleen cell suspensions of tumor-bearing animals (TBA) by passage of the cells on glass wool columns increased the Con A response of the remaining cells by fourfold to eightfold. Characterization of the suppressor population indicated that the cells were also adherent to nylon wool but not to plastic and contained a significantly increased proportion of surface immunoglobulin-bearing and complement receptor-bearing lymphocytes. Depletion of macrophages and T-cells did not remove the suppressive activity from the spleens of the TBA. The results were consistent with the identification of the suppressor cell as a B-cell."}
{"id": "PMID:203704", "title": "Isolation of a precipitating glycoprotein antigen from cell cultures persistently infected with bovine leukemia virus.", "content": "A procedure was developed to isolate a glycoprotein with precipitating antigen activity from fluids from fetal lamb kidney cell cultures persistently infected with bovine leukemia virus (BLV). The antigen was precipitated by ammonium sulfate and subjected to affinity chromatography on concanavalin A Sepharose. The glycoprotein was eluted with alpha-methyl-D-mannoside and was further purified by gel filtration over Sephadex G-100. Antigen activity was determined by agar gel immunodiffusion (AGID) reactions with serum from cattle infected with the virus. The major portion of the AGID activity was eluted from the Sephadex G-100 in the 60,000-dalton elution region. In some experiments, identical AGID activity was also found in the 18,000-dalton elution region. The larger protein was discovered to have a molecular weight of 58,000 daltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its designation as a glycoprotein was confirmed by carbohydrate-positive staining. The isolated BLV glycoprotein antigen did not contain ovine or bovine proteins as indicated by gel immunodiffusion.", "contents": "Isolation of a precipitating glycoprotein antigen from cell cultures persistently infected with bovine leukemia virus. A procedure was developed to isolate a glycoprotein with precipitating antigen activity from fluids from fetal lamb kidney cell cultures persistently infected with bovine leukemia virus (BLV). The antigen was precipitated by ammonium sulfate and subjected to affinity chromatography on concanavalin A Sepharose. The glycoprotein was eluted with alpha-methyl-D-mannoside and was further purified by gel filtration over Sephadex G-100. Antigen activity was determined by agar gel immunodiffusion (AGID) reactions with serum from cattle infected with the virus. The major portion of the AGID activity was eluted from the Sephadex G-100 in the 60,000-dalton elution region. In some experiments, identical AGID activity was also found in the 18,000-dalton elution region. The larger protein was discovered to have a molecular weight of 58,000 daltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its designation as a glycoprotein was confirmed by carbohydrate-positive staining. The isolated BLV glycoprotein antigen did not contain ovine or bovine proteins as indicated by gel immunodiffusion."}
{"id": "PMID:203705", "title": "Immune function in healthy relatives of patients with malignant disease.", "content": "Immune function studies of healthy members of families with multiple lymphoreticular neoplasms were compared with those of healthy members of families with multiple cancers and families with no known history of cancer. The lymphoma family group had a significantly elevated serum level of IgM and diminished responses to the Candida albicans skin test antigen and the T-cell mitogen concanavalin A. Subjects with Epstein-Barr virus-viral capsid antigen titers greater than or equal to 160 had lower responses to mitogens.", "contents": "Immune function in healthy relatives of patients with malignant disease. Immune function studies of healthy members of families with multiple lymphoreticular neoplasms were compared with those of healthy members of families with multiple cancers and families with no known history of cancer. The lymphoma family group had a significantly elevated serum level of IgM and diminished responses to the Candida albicans skin test antigen and the T-cell mitogen concanavalin A. Subjects with Epstein-Barr virus-viral capsid antigen titers greater than or equal to 160 had lower responses to mitogens."}
{"id": "PMID:203706", "title": "Epstein-Barr virus-associated and other antiviral antibodies during intense BCG administration to patients with Burkitt's lymphoma in remission.", "content": "Patients with Burkitt's lymphoma in chemotherapy-induced remission received through dermal scarifications one or two doses per week of approximately 3 X 10(8) living BCG organisms (Pasteur Institute vaccine). This treatment was always followed by usually rapid increases by 1--4 log2 steps in the antibody titers to Epstein-Barr virus (EBV)-associated cell membrane antigens. Titer increases of less than 2.5 log2 steps within the first month after the start of BCG treatment correlated with a significantly elevated frequency of extradural relapse as compared to that seen in patients with larger titer rises. During this time, antibodies to EBV-associated viral capsid antigens and early antigens of D and R specificity, as well as antibodies against herpes simplex, varicella, cytomegalovirus, measles, and respiratory syncytial virus antigens, did not show any consistent or impressive changes.", "contents": "Epstein-Barr virus-associated and other antiviral antibodies during intense BCG administration to patients with Burkitt's lymphoma in remission. Patients with Burkitt's lymphoma in chemotherapy-induced remission received through dermal scarifications one or two doses per week of approximately 3 X 10(8) living BCG organisms (Pasteur Institute vaccine). This treatment was always followed by usually rapid increases by 1--4 log2 steps in the antibody titers to Epstein-Barr virus (EBV)-associated cell membrane antigens. Titer increases of less than 2.5 log2 steps within the first month after the start of BCG treatment correlated with a significantly elevated frequency of extradural relapse as compared to that seen in patients with larger titer rises. During this time, antibodies to EBV-associated viral capsid antigens and early antigens of D and R specificity, as well as antibodies against herpes simplex, varicella, cytomegalovirus, measles, and respiratory syncytial virus antigens, did not show any consistent or impressive changes."}
{"id": "PMID:203707", "title": "Cell-surface antigens from human breast tumor cells.", "content": "Biochemical and immunologic studies on breast cancer with the use of cells from a human ductal cell carcinoma, BOT-2, were initiated. Antigens were extracted from the cells by mild sonication and purified by gel filtration chromatography. Only one of the three peaks from gel filtration chromatography reacted with antiserum prepared against whole BOT-2 cells. Analysis by polyacrylamide gel electrophoresis of the BOT-2 cell extract revealed many protein bands, whereas analysis of the antibody-reactive peak after gel filtration chromatography revealed fewer protein bands. Immunologic tests to identify human serum antibodies against BOT-2 cells or cell extracts were performed by fixed cell immunofluorescence, living cell membrane immunofluorescence, and indirect hemagglutination. Depending on the test, the sera from women with diagnosed, untreated mammary cancer were positive in 45--80% of the cases, whereas the sera from women without apparent breast diseases (controls) were positive in only 5--10% of the cases. The results suggested that the antigens from the BOT-2 cells will be useful in understanding the processes involved in human mammary neoplasia.", "contents": "Cell-surface antigens from human breast tumor cells. Biochemical and immunologic studies on breast cancer with the use of cells from a human ductal cell carcinoma, BOT-2, were initiated. Antigens were extracted from the cells by mild sonication and purified by gel filtration chromatography. Only one of the three peaks from gel filtration chromatography reacted with antiserum prepared against whole BOT-2 cells. Analysis by polyacrylamide gel electrophoresis of the BOT-2 cell extract revealed many protein bands, whereas analysis of the antibody-reactive peak after gel filtration chromatography revealed fewer protein bands. Immunologic tests to identify human serum antibodies against BOT-2 cells or cell extracts were performed by fixed cell immunofluorescence, living cell membrane immunofluorescence, and indirect hemagglutination. Depending on the test, the sera from women with diagnosed, untreated mammary cancer were positive in 45--80% of the cases, whereas the sera from women without apparent breast diseases (controls) were positive in only 5--10% of the cases. The results suggested that the antigens from the BOT-2 cells will be useful in understanding the processes involved in human mammary neoplasia."}
{"id": "PMID:203708", "title": "Cell-mediated immune response to simian oncornavirus antigens in pregnant women.", "content": "Tritiated thymidine incorporation into lymphocytes of 118 adult women was studied in the presence of mitomycin C-treated cells prepared from cell lines continuously producing Mason-Pfizer monkey virus (MPMV), baboon C-particle virus, or simian sarcoma virus (SSV) and in the presence of control cell lines documented for the absence of oncornaviruses. At the end of pregnancy, women who had 5-9 pregnancies showed a high frequency (53%) of specific positive responses to cells with MPMV antigens. The frequencies were 15% for pregnant women with smaller numbers of pregnancies and 3% for nonpregnant women with similar numbers of previous pregnancies as in the pregnancy group. None of these nonpregnant women had lymphocytes responding to stimulation by baboon C-virus antigens, but positive responses were obtained in 20 and 16% of the pregnant groups, respectively. No correlation was found between responses to MPMV or baboon C-virus antigens. Of 48 women (35 pregnant, 13 nonpregnant) who were tested for lymphocyte responses to SSV antigens, only 2 showed a positive response. The results indicated that two distinct antigens, related to MPMV and to baboon C-virus, may be expressed during pregnancy and may then induce a transient cell-mediated response.", "contents": "Cell-mediated immune response to simian oncornavirus antigens in pregnant women. Tritiated thymidine incorporation into lymphocytes of 118 adult women was studied in the presence of mitomycin C-treated cells prepared from cell lines continuously producing Mason-Pfizer monkey virus (MPMV), baboon C-particle virus, or simian sarcoma virus (SSV) and in the presence of control cell lines documented for the absence of oncornaviruses. At the end of pregnancy, women who had 5-9 pregnancies showed a high frequency (53%) of specific positive responses to cells with MPMV antigens. The frequencies were 15% for pregnant women with smaller numbers of pregnancies and 3% for nonpregnant women with similar numbers of previous pregnancies as in the pregnancy group. None of these nonpregnant women had lymphocytes responding to stimulation by baboon C-virus antigens, but positive responses were obtained in 20 and 16% of the pregnant groups, respectively. No correlation was found between responses to MPMV or baboon C-virus antigens. Of 48 women (35 pregnant, 13 nonpregnant) who were tested for lymphocyte responses to SSV antigens, only 2 showed a positive response. The results indicated that two distinct antigens, related to MPMV and to baboon C-virus, may be expressed during pregnancy and may then induce a transient cell-mediated response."}
{"id": "PMID:203709", "title": "Inhibition of deoxynucleotide-polymerizing enzyme activities of human leukemia lymphoblasts and simian sarcoma virus by tilorone and thirteen of its analogs.", "content": "Tilorone, which is 2,7-bis[2-(diethylamino)ethoxy]-9H-fluoren-9-one dihydrochloride, and 13 of its analogs inhibited human cellular DNA polymerases alpha and beta assayed with activated DNA as template and also cellular DNA polymerase gamma and DNA polymerase from simian sarcoma virus assayed with poly(A) (dT)12-18 as template. Terminal deoxynucleotidyltransferase (TdT),  which has no template requirement, was not inhibited by any of the 14 compounds when d(A)12-18 or d(G)12-18 was used as initiator. Three compounds did not inhibit TdT assayed with activated DNA as initiator, but 11 compounds did, and these 11 compounds were generally less inhibitory to TdT than to the other DNA polymerases. The three compounds that did not inhibit TdT assayed with activated DNA but did inhibit the other DNA polymerases will be useful in the characterization of TdT activity. Modifications of the polycyclic ring structure of tilorone and the kinds of substituent groups attached to the ring structures influenced the degree of inhibition of all enzymes.", "contents": "Inhibition of deoxynucleotide-polymerizing enzyme activities of human leukemia lymphoblasts and simian sarcoma virus by tilorone and thirteen of its analogs. Tilorone, which is 2,7-bis[2-(diethylamino)ethoxy]-9H-fluoren-9-one dihydrochloride, and 13 of its analogs inhibited human cellular DNA polymerases alpha and beta assayed with activated DNA as template and also cellular DNA polymerase gamma and DNA polymerase from simian sarcoma virus assayed with poly(A) (dT)12-18 as template. Terminal deoxynucleotidyltransferase (TdT),  which has no template requirement, was not inhibited by any of the 14 compounds when d(A)12-18 or d(G)12-18 was used as initiator. Three compounds did not inhibit TdT assayed with activated DNA as initiator, but 11 compounds did, and these 11 compounds were generally less inhibitory to TdT than to the other DNA polymerases. The three compounds that did not inhibit TdT assayed with activated DNA but did inhibit the other DNA polymerases will be useful in the characterization of TdT activity. Modifications of the polycyclic ring structure of tilorone and the kinds of substituent groups attached to the ring structures influenced the degree of inhibition of all enzymes."}
{"id": "PMID:203710", "title": "Investigation of human urogenital tract tumors of papovavirus etiology: brief communication.", "content": "Cells cultured from human urogenital cancer and other cancers as well as cells from noncancerous tissues were examined by immunofluorescent staining with antibodies to T-antigens and capsid antigens of papovaviruses BK virus (BKV), JC virus, and simian virus 40(SV40), and to capsid antigens of herpes simplex virus types 1 and 2 and human cytomegalovirus (CMV). Cells from early passage cultures of 123 primary tissues and from 14 continuous lines derived from transitional or renal cell carcinoma were tested. None of the cell preparations was specifically stained with any of the antisera. A serologic comparison of patients with bladder cancer, patients with prostate cancer, and normal control groups of BKV hemagglutination-inhibiting and SV40-neutralizing antibodies showed no differences among the 3 groups. None of the sera in the 3 groups had SV40 or BKV T-antibodies. In tests of supernatants of 35 primary cultures for presence of virus, a single isolation, that of a cytomegalovirus, was made. The study revealed no evidence that infection with papovaviruses of the SV40-polyoma subgroup has any part in the production of bladder and prostate cancer.", "contents": "Investigation of human urogenital tract tumors of papovavirus etiology: brief communication. Cells cultured from human urogenital cancer and other cancers as well as cells from noncancerous tissues were examined by immunofluorescent staining with antibodies to T-antigens and capsid antigens of papovaviruses BK virus (BKV), JC virus, and simian virus 40(SV40), and to capsid antigens of herpes simplex virus types 1 and 2 and human cytomegalovirus (CMV). Cells from early passage cultures of 123 primary tissues and from 14 continuous lines derived from transitional or renal cell carcinoma were tested. None of the cell preparations was specifically stained with any of the antisera. A serologic comparison of patients with bladder cancer, patients with prostate cancer, and normal control groups of BKV hemagglutination-inhibiting and SV40-neutralizing antibodies showed no differences among the 3 groups. None of the sera in the 3 groups had SV40 or BKV T-antibodies. In tests of supernatants of 35 primary cultures for presence of virus, a single isolation, that of a cytomegalovirus, was made. The study revealed no evidence that infection with papovaviruses of the SV40-polyoma subgroup has any part in the production of bladder and prostate cancer."}
{"id": "PMID:203711", "title": "Mammary tumors, hepatocellular carcinomas, and pancreatic islet changes in C3H-Avy Mice.", "content": "Studies of tumor incidence and assorted lesions found in 187 C3H-Avy mice throughout their natural life-spans revealed the following: Hepatocellular carcinomas occurred in 54.3% of males, mammary carcinomas in 95% of females, pancreatic islet cell adenomas in 9.4% of males and in no females, and pancreatic islet cell hyperplasia in 41% of males and 23% of fefemales. Islet cell hyperplasia and adenomas appeared to consist predominantly of alpha and delta cells. Multiple tumors, or hyperplasia, or both, of a single site or of multiple sites occurred as frequently in males as they did in females--49.6% and 51.7% respectively. The most frequent neoplasms were hepatocellular carcinomas and islet cell tumors or hyperplasia in males (45.7%) and multiple mammary tumors in females (30%). Heretofore unreported tumors found in this strain of mouse were 12 islet cell adenomas, 2 spindle cell tumors of the meninges and olfactory lobes, a squamous cell carcinoma of the nasal turbinates, and a schwannoma of the spermatic cord.", "contents": "Mammary tumors, hepatocellular carcinomas, and pancreatic islet changes in C3H-Avy Mice. Studies of tumor incidence and assorted lesions found in 187 C3H-Avy mice throughout their natural life-spans revealed the following: Hepatocellular carcinomas occurred in 54.3% of males, mammary carcinomas in 95% of females, pancreatic islet cell adenomas in 9.4% of males and in no females, and pancreatic islet cell hyperplasia in 41% of males and 23% of fefemales. Islet cell hyperplasia and adenomas appeared to consist predominantly of alpha and delta cells. Multiple tumors, or hyperplasia, or both, of a single site or of multiple sites occurred as frequently in males as they did in females--49.6% and 51.7% respectively. The most frequent neoplasms were hepatocellular carcinomas and islet cell tumors or hyperplasia in males (45.7%) and multiple mammary tumors in females (30%). Heretofore unreported tumors found in this strain of mouse were 12 islet cell adenomas, 2 spindle cell tumors of the meninges and olfactory lobes, a squamous cell carcinoma of the nasal turbinates, and a schwannoma of the spermatic cord."}
{"id": "PMID:203712", "title": "Oncornavirus lytic activity in the serum of gibbon apes.", "content": "Fresh blood serum from normal gibbon apes (Hylobates lar) contained heat-sensitive lytic activity for various mammalian oncornaviruses. Lytic activity quantitatively similar to that in gibbon serum was demonstrated in serum from three other primate species, including man; it was demonstrated to be low or absent in lower mammalian species with the exception of domestic cats, which had intermediate levels of serum lytic activity. Gibbons that acquired infectious gibbon ape leukemia virus, either naturally by exposure to a virus-shedding ape or experimentally by deliberate virus inoculation, had the same levels of serum lytic activity as did unexposed gibbons that had no detectable antibodies to gibbon ape leukemia virus. A leukemic-viremic gibbon had low or absent serum oncornavirus lytic activity. These results indicated that serum lytic activity does not necessarily protect against infection by oncornaviruses, although it may limit virus replication and/or dissemination.", "contents": "Oncornavirus lytic activity in the serum of gibbon apes. Fresh blood serum from normal gibbon apes (Hylobates lar) contained heat-sensitive lytic activity for various mammalian oncornaviruses. Lytic activity quantitatively similar to that in gibbon serum was demonstrated in serum from three other primate species, including man; it was demonstrated to be low or absent in lower mammalian species with the exception of domestic cats, which had intermediate levels of serum lytic activity. Gibbons that acquired infectious gibbon ape leukemia virus, either naturally by exposure to a virus-shedding ape or experimentally by deliberate virus inoculation, had the same levels of serum lytic activity as did unexposed gibbons that had no detectable antibodies to gibbon ape leukemia virus. A leukemic-viremic gibbon had low or absent serum oncornavirus lytic activity. These results indicated that serum lytic activity does not necessarily protect against infection by oncornaviruses, although it may limit virus replication and/or dissemination."}
{"id": "PMID:203713", "title": "Spontaneous and induced preleukemia cells in C57BL/6 mice:brief communication.", "content": "A transplantation bioassay method was used to verify the presence of preleukemia cells in C57BL/6 mice shortly after leukemogenic treatment or in relation to age increase. Preleukemia cells were identified mainly among bone marrow cells of old C57BL/6 mice or within 10 to 30 days after leukemogenic treatment of young mice with radiation-induced leukemia virus variants, fractionated doses of irradiation, or 7,12-dimethylbenz[a]anthracene (DMBA), although the overt disease did not occur until many months later. Mice could carry preleukemia cells without necessarily developing overt leukemia. Since the leukemogenic agents used in the present studies induced T-leukemias, the role of the thymus in the induction of preleukemia cells was tested. Thymectomy affected viral transformation but did not diminish the number of preleukemia cells induced by DMBA or X-ray.", "contents": "Spontaneous and induced preleukemia cells in C57BL/6 mice:brief communication. A transplantation bioassay method was used to verify the presence of preleukemia cells in C57BL/6 mice shortly after leukemogenic treatment or in relation to age increase. Preleukemia cells were identified mainly among bone marrow cells of old C57BL/6 mice or within 10 to 30 days after leukemogenic treatment of young mice with radiation-induced leukemia virus variants, fractionated doses of irradiation, or 7,12-dimethylbenz[a]anthracene (DMBA), although the overt disease did not occur until many months later. Mice could carry preleukemia cells without necessarily developing overt leukemia. Since the leukemogenic agents used in the present studies induced T-leukemias, the role of the thymus in the induction of preleukemia cells was tested. Thymectomy affected viral transformation but did not diminish the number of preleukemia cells induced by DMBA or X-ray."}
{"id": "PMID:203715", "title": "The clinical utility of ipsilateral stapedius reflex tests.", "content": "Ipsilateral stapedius reflex testing has been evaluated in 166 patients. It proves of value in defining the state of an ear (1) opposite to a unilateral conductive loss; (2) the less hard-of-hearing ear in the presence of bilateral asymmetrical sensorineural hearing losses where the worse ear has sufficiently severe loss to prevent a contralateral reflex from being elicited; (3) in patients with absent contralateral acoustic reflexes at 500, 1000, and 2000 Hz; and (4) in suspected central lesions. The test is still bedevilled by artifacts which are produced in the ear rather than the machine; atypical results must be evaluated with extreme caution.", "contents": "The clinical utility of ipsilateral stapedius reflex tests. Ipsilateral stapedius reflex testing has been evaluated in 166 patients. It proves of value in defining the state of an ear (1) opposite to a unilateral conductive loss; (2) the less hard-of-hearing ear in the presence of bilateral asymmetrical sensorineural hearing losses where the worse ear has sufficiently severe loss to prevent a contralateral reflex from being elicited; (3) in patients with absent contralateral acoustic reflexes at 500, 1000, and 2000 Hz; and (4) in suspected central lesions. The test is still bedevilled by artifacts which are produced in the ear rather than the machine; atypical results must be evaluated with extreme caution."}
{"id": "PMID:203716", "title": "Effect of rhesus or vervet cytomegalovirus infection of DNA synthesis in untreated and 5-iodo-2'-deoxyuridine-arrested cells.", "content": "Infection of permissive cells with either rhesus or vervet cytomegalovirus resulted in suppression of cellular DNA synthesis, only viral DNA was resolved by isopycnic centrifugation after 24 h postinoculation. Infection of 5-iodo-2'-deoxyuridine (IUdR)-arrested cells with either of the simian cytomegaloviruses, however, induced synthesis of cellular DNA of normal density; synthesis of cellular DNA substituted with IUdR as evidenced by resolution of a heavy DNA peak after isopycnic centrifugation was not observed. Stimulation of DNA synthesis in IUdR-arrested cells was not observed with virus inactivated with UV light.", "contents": "Effect of rhesus or vervet cytomegalovirus infection of DNA synthesis in untreated and 5-iodo-2'-deoxyuridine-arrested cells. Infection of permissive cells with either rhesus or vervet cytomegalovirus resulted in suppression of cellular DNA synthesis, only viral DNA was resolved by isopycnic centrifugation after 24 h postinoculation. Infection of 5-iodo-2'-deoxyuridine (IUdR)-arrested cells with either of the simian cytomegaloviruses, however, induced synthesis of cellular DNA of normal density; synthesis of cellular DNA substituted with IUdR as evidenced by resolution of a heavy DNA peak after isopycnic centrifugation was not observed. Stimulation of DNA synthesis in IUdR-arrested cells was not observed with virus inactivated with UV light."}
{"id": "PMID:203717", "title": "Molecular mechanisms involved in the differential expression of gag gene products by clonal isolates of a primate sarcoma virus.", "content": "Clonal isolates of an early passage stock of woolly monkey sarcoma virus (WSV) have been shown to code for different numbers of woolly monkey helper leukemia virus gag gene products. In the present report, the molecular mechanisms responsible for their differential expression of gag gene products have been analyzed. Three WSV RNA genomes were shown to possess sedimentation coefficients consistent with the differences demonstrated in their allotments of helper viral sequences. The WSV variant (WSV clone 9) that expressed no detectable proteins was shown to contain the largest amount of helper viral information. Moreover, there was no additive hybridization of the WLV complementary DNA probe by RNA of this WSV clone and that of a WSV clone coding for several gag gene products. These results suggest that the lack of expression of gag gene products by WSV clone 9 is not due to a major deletion of helper viral gag gene sequences. Similar levels of WLV-specific RNA were demonstrated in cells nonproductively transformed by each WSV clone, arguing that the ability to express gag gene proteins was not related to the magnitude of viral RNA transcription. Taken together, the results are most consistent with a mechanism by which small deletions or point mutations in the genomes of some WSV variants result in premature termination of translation or synthesis of immunologically nonreactive gag gene proteins. The present findings have implications concerning the effects of evolutionary selective pressures on helper viral genetic information in mammalian transforming viruses.", "contents": "Molecular mechanisms involved in the differential expression of gag gene products by clonal isolates of a primate sarcoma virus. Clonal isolates of an early passage stock of woolly monkey sarcoma virus (WSV) have been shown to code for different numbers of woolly monkey helper leukemia virus gag gene products. In the present report, the molecular mechanisms responsible for their differential expression of gag gene products have been analyzed. Three WSV RNA genomes were shown to possess sedimentation coefficients consistent with the differences demonstrated in their allotments of helper viral sequences. The WSV variant (WSV clone 9) that expressed no detectable proteins was shown to contain the largest amount of helper viral information. Moreover, there was no additive hybridization of the WLV complementary DNA probe by RNA of this WSV clone and that of a WSV clone coding for several gag gene products. These results suggest that the lack of expression of gag gene products by WSV clone 9 is not due to a major deletion of helper viral gag gene sequences. Similar levels of WLV-specific RNA were demonstrated in cells nonproductively transformed by each WSV clone, arguing that the ability to express gag gene proteins was not related to the magnitude of viral RNA transcription. Taken together, the results are most consistent with a mechanism by which small deletions or point mutations in the genomes of some WSV variants result in premature termination of translation or synthesis of immunologically nonreactive gag gene proteins. The present findings have implications concerning the effects of evolutionary selective pressures on helper viral genetic information in mammalian transforming viruses."}
{"id": "PMID:203718", "title": "Human lymphoblastoid cells as hosts for parvoviruses H-1 and rat virus.", "content": "A human T-cell line (Molt-4) was shown by viral hemagglutination and infectivity assays to support the replication of rat virus (RV) and H-1 virus. In addition, H-1 virus, but not RV, multiplied in two human B-cell lines, AV-1 and NC-37. The ability to bind radioactively labeled RV was demonstrated for each of the cell lines, but viral adsorption occurred to a greater degree with Molt-4 cells than with either AV-1 or NC-37 cells. After challenge with RV, virus-specific antigens were detected in cells of the B-cell lines by the indirect immunofluorescence technique. Infection of AV-1 or NC-37 cells by RV apparently results in an abortive cycle of virus replication. Differences among the three cell lines that might influence with H-1 virus or RV are discussed.", "contents": "Human lymphoblastoid cells as hosts for parvoviruses H-1 and rat virus. A human T-cell line (Molt-4) was shown by viral hemagglutination and infectivity assays to support the replication of rat virus (RV) and H-1 virus. In addition, H-1 virus, but not RV, multiplied in two human B-cell lines, AV-1 and NC-37. The ability to bind radioactively labeled RV was demonstrated for each of the cell lines, but viral adsorption occurred to a greater degree with Molt-4 cells than with either AV-1 or NC-37 cells. After challenge with RV, virus-specific antigens were detected in cells of the B-cell lines by the indirect immunofluorescence technique. Infection of AV-1 or NC-37 cells by RV apparently results in an abortive cycle of virus replication. Differences among the three cell lines that might influence with H-1 virus or RV are discussed."}
{"id": "PMID:203719", "title": "Quantitation and localization of Rous sarcoma virus-specific RNA in transformed and revertant field vole cells.", "content": "Hybridization analysis of RNA from transformed clones of Rous sarcoma virus (RSV)-infected field vole cells and revertant subclones indicated the presence of similar amounts of viral-specific RNA in both cell types. Employing both a relatively uniform and representative complementary DNA probe and genomelength complementary DNA, we have demonstrated that the majority of RSV proviral DNA is transcribed into viral-specific RNA in both transformed and revertant clones. The viral-specific RNA is present in several size classes, the largest of which is genome-length 35S RNA. Studies on the intracellular distribution of viral-specific RNA indicate that both transformed and revertant cells contain viral RNA in their cytoplasm. Furthermore, the bulk of viral-specific nucleotide sequences are also associated with polyribosomes in both cell types. These data indicate that, contrary to previously reported studies with other retrovirus-revertant cell systems, the entire RSV provirus DNA is transcribed into viral RNA similarly in both transformed and revertant vole cells. Since we have previously demonstrated similarities in sarcoma-specific viral RNA in both revertant and transformed vole cells, these data collectively indicate that the loss of the transformed phenotype does not reflect changes in transcription of all or part of the RSV provirus, or the processing, transport, or polyribosome association of viral-specific RNA representing the entire RSV genome.", "contents": "Quantitation and localization of Rous sarcoma virus-specific RNA in transformed and revertant field vole cells. Hybridization analysis of RNA from transformed clones of Rous sarcoma virus (RSV)-infected field vole cells and revertant subclones indicated the presence of similar amounts of viral-specific RNA in both cell types. Employing both a relatively uniform and representative complementary DNA probe and genomelength complementary DNA, we have demonstrated that the majority of RSV proviral DNA is transcribed into viral-specific RNA in both transformed and revertant clones. The viral-specific RNA is present in several size classes, the largest of which is genome-length 35S RNA. Studies on the intracellular distribution of viral-specific RNA indicate that both transformed and revertant cells contain viral RNA in their cytoplasm. Furthermore, the bulk of viral-specific nucleotide sequences are also associated with polyribosomes in both cell types. These data indicate that, contrary to previously reported studies with other retrovirus-revertant cell systems, the entire RSV provirus DNA is transcribed into viral RNA similarly in both transformed and revertant vole cells. Since we have previously demonstrated similarities in sarcoma-specific viral RNA in both revertant and transformed vole cells, these data collectively indicate that the loss of the transformed phenotype does not reflect changes in transcription of all or part of the RSV provirus, or the processing, transport, or polyribosome association of viral-specific RNA representing the entire RSV genome."}
{"id": "PMID:203720", "title": "Polyoma virus complementary RNA directs the in vitro synthesis of capsid proteins VP1 and VP2.", "content": "Polyoma virus complementary RNA, synthesized in vitro by using highly purified Escherichia coli RNA polymerase and nondefective form I polyoma DNA, was translated in a wheat germ cell-free system. Polypeptides were synthesized that comigrated on sodium dodecyl sulfate-polyacrylamide gels with the polyoma capsid proteins VP1 and VP2, although most of the cell-free products were of smaller molecular weights. The VP1-size protein specifically immunoprecipitated with anti-polyoma virus serum, and upon digestion by trypsin yielded [35S]methionine-labeled tryptic peptides that co-chromatographed with the [3H]methionine-labeled tryptic peptides of virion-derived VP1 on both cation-exchange and anion-exchange resins. The VP2-size in vitro product contained all the virion VP2 methionine-labeled tryptic peptides, as shown by cation- and anion-exchange chromatography and two-dimensional fingerprinting on cellulose. We conclude that full-length polyoma VP1 and VP2 are synthesized in response to complementary RNA and consequently that the viral capsid proteins VP1, VP2, and VP3 are entirely virus coded.", "contents": "Polyoma virus complementary RNA directs the in vitro synthesis of capsid proteins VP1 and VP2. Polyoma virus complementary RNA, synthesized in vitro by using highly purified Escherichia coli RNA polymerase and nondefective form I polyoma DNA, was translated in a wheat germ cell-free system. Polypeptides were synthesized that comigrated on sodium dodecyl sulfate-polyacrylamide gels with the polyoma capsid proteins VP1 and VP2, although most of the cell-free products were of smaller molecular weights. The VP1-size protein specifically immunoprecipitated with anti-polyoma virus serum, and upon digestion by trypsin yielded [35S]methionine-labeled tryptic peptides that co-chromatographed with the [3H]methionine-labeled tryptic peptides of virion-derived VP1 on both cation-exchange and anion-exchange resins. The VP2-size in vitro product contained all the virion VP2 methionine-labeled tryptic peptides, as shown by cation- and anion-exchange chromatography and two-dimensional fingerprinting on cellulose. We conclude that full-length polyoma VP1 and VP2 are synthesized in response to complementary RNA and consequently that the viral capsid proteins VP1, VP2, and VP3 are entirely virus coded."}
{"id": "PMID:203721", "title": "Cellular and cell-free synthesis of simian virus 40 T-antigens in permissive and transformed cells.", "content": "mRNA extracted from a variety of simian virus 40 (SV40)-infected monkey cell lines directs the cell-free synthesis of viral T-antigen polypeptides with molecular weights estimated as 90,000 and 17,000. However, the size, abundance, and distribution of these T-antigens synthesized in vivo vary greatly over a range of permissive and transformed cell lines. To establish whether differences in the size of T-antigen polypeptides can be correlated with the transformed or lytic state, recently developed lines of SV40-transformed monkey cells that are permissive to lytic superinfection were analyzed for T-antigen. In these cells, regardless of the state of viral infection, the size and pattern of T-antigen are the same. However, species differences in the largest size of T-antigen are the same. However, species differences in the largest size of T-antigen do exist. In addition to the 90,000 T-antigen, mouse SV3T3 cells contain a 94,000 T-antigen polypeptide as well. Unlike the size variations in monkey cells, which are due to modification of T-antigen polypeptides, the 94,000 SV3T3 T-antigen results from an altered mRNA, since the cell-free products of SV3T3 mRNA also contains the 94,000 T-antigen polypeptide.", "contents": "Cellular and cell-free synthesis of simian virus 40 T-antigens in permissive and transformed cells. mRNA extracted from a variety of simian virus 40 (SV40)-infected monkey cell lines directs the cell-free synthesis of viral T-antigen polypeptides with molecular weights estimated as 90,000 and 17,000. However, the size, abundance, and distribution of these T-antigens synthesized in vivo vary greatly over a range of permissive and transformed cell lines. To establish whether differences in the size of T-antigen polypeptides can be correlated with the transformed or lytic state, recently developed lines of SV40-transformed monkey cells that are permissive to lytic superinfection were analyzed for T-antigen. In these cells, regardless of the state of viral infection, the size and pattern of T-antigen are the same. However, species differences in the largest size of T-antigen are the same. However, species differences in the largest size of T-antigen do exist. In addition to the 90,000 T-antigen, mouse SV3T3 cells contain a 94,000 T-antigen polypeptide as well. Unlike the size variations in monkey cells, which are due to modification of T-antigen polypeptides, the 94,000 SV3T3 T-antigen results from an altered mRNA, since the cell-free products of SV3T3 mRNA also contains the 94,000 T-antigen polypeptide."}
{"id": "PMID:203722", "title": "Possible role of the 72,000 dalton DNA-binding protein in regulation of adenovirus type 5 early gene expression.", "content": "Relative abundances of early virus RNA species in the cytoplasm of cells infected with wild-type adenovirus type 5 (WT Ad5) and a temperature-sensitive \"early\" mutant, H5ts125 (ts125), were compared by hybridization kinetics using separated strands of HindIII restriction endonuclease fragments of Ad5 DNA. 1-beta-D-Arabinofuranosylcytosine (ara-C) was used to limit transcription to early virus genes in cells infected by WT virus. At 40.5 degrees C, a restrictive temperature for ts125, three to seven times as much virus RNA from all four early regions of the genome accumulated in the cytoplasm of cells infected by the mutant as accumulated in cells infected by WT. At 32 degrees C, no such difference in the relative abundances of cytoplasmic virus RNA was observed. The capacity to synthesize a 72,000-dalton (72K) virus polypeptide, presumably the single-stranded DNA-binding protein that is defective in ts125 at restrictive temperatures, was compared in cells infected at 40.5 degrees C in the presence of ara-C with the mutant or WT Ad5. The rate of 72K polypeptide synthesis, measured by sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis of [35S]methionine-labeled polypeptides and autoradiography, was greater at 15 h after infection in ts125-infected cells than in cells infected by WT. A time course experiment showed that the rate of synthesis of the 72K polypeptide increased continuously in ts125-infected cells during the first 15 h of infection, relative to the rate in WT-infected cells. These data are consistent with the hypothesis that Ad5 early gene expression is modulated by the product of an early gene, the 72K DNA-binding protein.", "contents": "Possible role of the 72,000 dalton DNA-binding protein in regulation of adenovirus type 5 early gene expression. Relative abundances of early virus RNA species in the cytoplasm of cells infected with wild-type adenovirus type 5 (WT Ad5) and a temperature-sensitive \"early\" mutant, H5ts125 (ts125), were compared by hybridization kinetics using separated strands of HindIII restriction endonuclease fragments of Ad5 DNA. 1-beta-D-Arabinofuranosylcytosine (ara-C) was used to limit transcription to early virus genes in cells infected by WT virus. At 40.5 degrees C, a restrictive temperature for ts125, three to seven times as much virus RNA from all four early regions of the genome accumulated in the cytoplasm of cells infected by the mutant as accumulated in cells infected by WT. At 32 degrees C, no such difference in the relative abundances of cytoplasmic virus RNA was observed. The capacity to synthesize a 72,000-dalton (72K) virus polypeptide, presumably the single-stranded DNA-binding protein that is defective in ts125 at restrictive temperatures, was compared in cells infected at 40.5 degrees C in the presence of ara-C with the mutant or WT Ad5. The rate of 72K polypeptide synthesis, measured by sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis of [35S]methionine-labeled polypeptides and autoradiography, was greater at 15 h after infection in ts125-infected cells than in cells infected by WT. A time course experiment showed that the rate of synthesis of the 72K polypeptide increased continuously in ts125-infected cells during the first 15 h of infection, relative to the rate in WT-infected cells. These data are consistent with the hypothesis that Ad5 early gene expression is modulated by the product of an early gene, the 72K DNA-binding protein."}
{"id": "PMID:203723", "title": "Inhibition of transcription by immunoglobulins directed against the ribonucleoprotein of homotypic and heterotypic vesicular stomatitis viruses.", "content": "Specific antisera were raised by immunization of rabbits with purified nucleocapsids containing only RNA and N protein (ribonucleoprotein, RNP) obtained from vesicular stomatitis (VS) virions of the Indiana (VSInd) and the New Jersey (VSNJ) serotypes. The specificity of anti-RNPInd serum was demonstrated by selective precipitation of homotypic RNPInd devoid of L and NS proteins; anti-RNPInd serum also selectively precipitated soluble N protein present in cytoplasm of infected cells, but co-precipitated a limited amount of contaminating soluble NS protein. Immunoglobulins prepared from each homotypic antiserum markedly inhibited in vitro transcription of VSInd and VSNJ virions. Anti-RNPInd and anti-RNPNJ immunoglobulins also exhibited cross-reactivity by inhibiting transcription of heterotypic virions, but only to a much lesser degree than in the homotypic reaction. Anti-RNPInd immunoglobulin did not inhibit transcription of the antigenically unrelated Chandipura rhabdovirus, but anti-RNPNJ immunoglobulin did to a very limited extent. The transcription inhibitory activity of anti-RNPInd immunoglobulin was not dependent on RNP immunoprecipitation activity, which could be diluted out well before loss of antitranscriptase activity. Anti-RNPind immunoglobulin appeared to exert its effect on transcription by blocking elongation rather than initiation or reinitiation of RNA transcripts.", "contents": "Inhibition of transcription by immunoglobulins directed against the ribonucleoprotein of homotypic and heterotypic vesicular stomatitis viruses. Specific antisera were raised by immunization of rabbits with purified nucleocapsids containing only RNA and N protein (ribonucleoprotein, RNP) obtained from vesicular stomatitis (VS) virions of the Indiana (VSInd) and the New Jersey (VSNJ) serotypes. The specificity of anti-RNPInd serum was demonstrated by selective precipitation of homotypic RNPInd devoid of L and NS proteins; anti-RNPInd serum also selectively precipitated soluble N protein present in cytoplasm of infected cells, but co-precipitated a limited amount of contaminating soluble NS protein. Immunoglobulins prepared from each homotypic antiserum markedly inhibited in vitro transcription of VSInd and VSNJ virions. Anti-RNPInd and anti-RNPNJ immunoglobulins also exhibited cross-reactivity by inhibiting transcription of heterotypic virions, but only to a much lesser degree than in the homotypic reaction. Anti-RNPInd immunoglobulin did not inhibit transcription of the antigenically unrelated Chandipura rhabdovirus, but anti-RNPNJ immunoglobulin did to a very limited extent. The transcription inhibitory activity of anti-RNPInd immunoglobulin was not dependent on RNP immunoprecipitation activity, which could be diluted out well before loss of antitranscriptase activity. Anti-RNPind immunoglobulin appeared to exert its effect on transcription by blocking elongation rather than initiation or reinitiation of RNA transcripts."}
{"id": "PMID:203724", "title": "In vitro transcription of mouse mammary tumor virus RNA into DNA.", "content": "The in vitro transcription of the B-type mouse mammary tumor virus RNA into DNA is similar to that obtained with certain C-type viruses: synthesis can be initiated on an RNA primer molecule approximately the size of a tRNA, and a unique linkage (rA-dC) exists between this primer and the DNA product.", "contents": "In vitro transcription of mouse mammary tumor virus RNA into DNA. The in vitro transcription of the B-type mouse mammary tumor virus RNA into DNA is similar to that obtained with certain C-type viruses: synthesis can be initiated on an RNA primer molecule approximately the size of a tRNA, and a unique linkage (rA-dC) exists between this primer and the DNA product."}
{"id": "PMID:203725", "title": "In vitro termination of adenovirus DNA synthesis by a soluble replication complex.", "content": "The double-stranded DNA from a soluble DNA replication complex that was labeled with deoxyribonucleoside triphosphates and completed in vitro was digested with EcoRI, Sma I, and Hpa I restriction endonucleases. All regions of the adenovirus type 2 genome were labeled in vitro, but restriction fragments derived from the ends of the DNA molecules were relatively more highly labeled than those derived from internal regions. The in vitro endogenous DNA polymerase reaction also exhibited strand-specific labeling near the molecular ends, in that restriciton fragments from the left end were labeled predominantly in the r strand and fragments from the right end were labeled predominantly in the l strand.", "contents": "In vitro termination of adenovirus DNA synthesis by a soluble replication complex. The double-stranded DNA from a soluble DNA replication complex that was labeled with deoxyribonucleoside triphosphates and completed in vitro was digested with EcoRI, Sma I, and Hpa I restriction endonucleases. All regions of the adenovirus type 2 genome were labeled in vitro, but restriction fragments derived from the ends of the DNA molecules were relatively more highly labeled than those derived from internal regions. The in vitro endogenous DNA polymerase reaction also exhibited strand-specific labeling near the molecular ends, in that restriciton fragments from the left end were labeled predominantly in the r strand and fragments from the right end were labeled predominantly in the l strand."}
{"id": "PMID:203726", "title": "Laetrile toxicity studies in dogs.", "content": "Dogs were fed laetrile and fresh, sweet almonds under various conditions. The doses of laetrile were similar to those prescribed for patients with cancer and ranged on a basis of gram to square meter from an equivalent of the oral dose for man to five times this dose. Six of the ten dogs died of cyanide poisoning. One dog recovered, and three dogs, at the time of sacrifice, demonstrated various levels of neurologic impairment, ranging from difficulty in walking to coma. These studies demonstrate that oral laetrile is highly toxic when taken with some common table foods. We predict that there will be an increased incidence of cyanide poisoning in man as laetrile becomes more readily available.", "contents": "Laetrile toxicity studies in dogs. Dogs were fed laetrile and fresh, sweet almonds under various conditions. The doses of laetrile were similar to those prescribed for patients with cancer and ranged on a basis of gram to square meter from an equivalent of the oral dose for man to five times this dose. Six of the ten dogs died of cyanide poisoning. One dog recovered, and three dogs, at the time of sacrifice, demonstrated various levels of neurologic impairment, ranging from difficulty in walking to coma. These studies demonstrate that oral laetrile is highly toxic when taken with some common table foods. We predict that there will be an increased incidence of cyanide poisoning in man as laetrile becomes more readily available."}
{"id": "PMID:203729", "title": "Diabetes mellitus following rodenticide ingestion in man.", "content": "Ketotic, insulin-requiring diabetes mellitus and a severe peripheral neuropathy developed in a previously healthy 25-year-old man several days after he attempted suicide with rat poison containing N-3-pyridylmethyl N'-p-nitrophenyl urea. Study of islet-cell function ten months after ingestion showed a reduced disappearance rate of intravenous glucose and depressed C-peptide response to intravenous glucose when compared with a normal control but no impairment of glucagon release after intravenous arginine stimulation. Nerve conduction studies demonstrated severe sensory and mild motor neuropathy. Quadriceps capillary basement membrane thickness was in the diabetic range. Because at least 15 similar occurrences have been reported to the manufacturer, this agent appears to be diabetogenic in man, probably causing beta-cell destruction. Niacinamide, which can prevent glucose intolerance in both streptozocin- and alloxan-treated animals and prevents death in rats given this rodenticide, may be a useful antidote.", "contents": "Diabetes mellitus following rodenticide ingestion in man. Ketotic, insulin-requiring diabetes mellitus and a severe peripheral neuropathy developed in a previously healthy 25-year-old man several days after he attempted suicide with rat poison containing N-3-pyridylmethyl N'-p-nitrophenyl urea. Study of islet-cell function ten months after ingestion showed a reduced disappearance rate of intravenous glucose and depressed C-peptide response to intravenous glucose when compared with a normal control but no impairment of glucagon release after intravenous arginine stimulation. Nerve conduction studies demonstrated severe sensory and mild motor neuropathy. Quadriceps capillary basement membrane thickness was in the diabetic range. Because at least 15 similar occurrences have been reported to the manufacturer, this agent appears to be diabetogenic in man, probably causing beta-cell destruction. Niacinamide, which can prevent glucose intolerance in both streptozocin- and alloxan-treated animals and prevents death in rats given this rodenticide, may be a useful antidote."}
{"id": "PMID:203737", "title": "Hepatic tumors, surgical treatment and its results.", "content": "During the period from March 1954 to June 1976, 489 cases of hepatic tumors were experienced at the Department of Surgery, National Taiwan University Hospital. The pathological classification are: Hemangioma 5; Cystic hamartoma 2; Hemangioendothelioma 2; Non-parasitic localized cyst 5; Polycystic liver 9; Tuberculoma 1; Actinomycosis 1; Hyperplasia 1; Adenoma 1; Primary liver sarcoma 2; Primary liver cancer 442; and Metastatic liver cancer 18. Of the 489 hepatic tumors, two cases were treated with excision, 148 cases with hepatic lobectomy and nine cases of polycystic liver were treated with fenestration. Benign hepatic tumors are all well up to eight years after the operation, 14 cases of primary liver cancer survived five to 17 years after hepatic lobectomy.", "contents": "Hepatic tumors, surgical treatment and its results. During the period from March 1954 to June 1976, 489 cases of hepatic tumors were experienced at the Department of Surgery, National Taiwan University Hospital. The pathological classification are: Hemangioma 5; Cystic hamartoma 2; Hemangioendothelioma 2; Non-parasitic localized cyst 5; Polycystic liver 9; Tuberculoma 1; Actinomycosis 1; Hyperplasia 1; Adenoma 1; Primary liver sarcoma 2; Primary liver cancer 442; and Metastatic liver cancer 18. Of the 489 hepatic tumors, two cases were treated with excision, 148 cases with hepatic lobectomy and nine cases of polycystic liver were treated with fenestration. Benign hepatic tumors are all well up to eight years after the operation, 14 cases of primary liver cancer survived five to 17 years after hepatic lobectomy."}
{"id": "PMID:203738", "title": "Tumor embolism in the right atrium after hepatic artery ligation for hepatoma.", "content": "A case of tumor embolism in the right atrium after hepatic artery ligation for hepatoma was reported. Patient was a 55 year old male complaining of upper abdominal pain. Preoperative angiogram and scintigram revealed multinodular hepatomas in the right and middle his condition gradually deteriorated thereafter and sudden hypotension occurred on the 22nd postoperative day with a fatal sequela. At autopsy, the orifice of the right atrium was impacted by a tumor embolus. The cause of death seemed to be attributable to this embolus liberated from the hepatic veins. Accordingly, we emphasize the necessity of careful angiographic evaluation not only of the hepatic inflow but of the outflow tract in performing hepatic artery ligation as a treatment of nonresectable hepatoma.", "contents": "Tumor embolism in the right atrium after hepatic artery ligation for hepatoma. A case of tumor embolism in the right atrium after hepatic artery ligation for hepatoma was reported. Patient was a 55 year old male complaining of upper abdominal pain. Preoperative angiogram and scintigram revealed multinodular hepatomas in the right and middle his condition gradually deteriorated thereafter and sudden hypotension occurred on the 22nd postoperative day with a fatal sequela. At autopsy, the orifice of the right atrium was impacted by a tumor embolus. The cause of death seemed to be attributable to this embolus liberated from the hepatic veins. Accordingly, we emphasize the necessity of careful angiographic evaluation not only of the hepatic inflow but of the outflow tract in performing hepatic artery ligation as a treatment of nonresectable hepatoma."}
{"id": "PMID:203740", "title": "[Microcirculatory hemostasis and its changes in cardiovascular diseases].", "content": "The indices of microcirculatory hemostasis were studied in 955 persons, 200 of whom were healthy while 755 had diseases of the heart and vessels. The results were compared with blood fibrinolytic and coagulation activity and with the functional condition of the basophil-mast cell apparatus. A reverse trend in the functional shifts of microcirculatory and plasmo-coagulative hemostasis in the reaction of emergency adaptation was established. Delayed formation and increased resistance of platelet aggregates with simultaneous decrease in the number of platelets in circulation were revealed in cardiovascular diseases during a remission, which reflects intensified expenditure of the platelets or their aggregation energy in the microcirculatory channel. The administration of exogenous heparin, just like the period of basophil degranulation in stresses of various origin, is attended with distinct platelet hyperfunction which allows small doses of heparin to be used for the prevention of diapedetic hemorrhages in hypertensive disease.", "contents": "[Microcirculatory hemostasis and its changes in cardiovascular diseases]. The indices of microcirculatory hemostasis were studied in 955 persons, 200 of whom were healthy while 755 had diseases of the heart and vessels. The results were compared with blood fibrinolytic and coagulation activity and with the functional condition of the basophil-mast cell apparatus. A reverse trend in the functional shifts of microcirculatory and plasmo-coagulative hemostasis in the reaction of emergency adaptation was established. Delayed formation and increased resistance of platelet aggregates with simultaneous decrease in the number of platelets in circulation were revealed in cardiovascular diseases during a remission, which reflects intensified expenditure of the platelets or their aggregation energy in the microcirculatory channel. The administration of exogenous heparin, just like the period of basophil degranulation in stresses of various origin, is attended with distinct platelet hyperfunction which allows small doses of heparin to be used for the prevention of diapedetic hemorrhages in hypertensive disease."}
{"id": "PMID:203742", "title": "[Diagnosis and treatment of ocular myasthenia (author's transl)].", "content": "After discussion of the modern concepts of pathophysiology of ocular myasthenia the ocular symptoms such as ptosis and eye muscle palsies are discussed. As important diagnostic sign the Simpson lid fatigue test before and after application of Tensilon is described. For diagnosis of myasthenic eye muscle palsies electrooculography has a special significance especially in connection with the application of Edrophonium, which normalizes myasthenic hypometric saccades and transforms them even in hypermetric saccades. In doubtful cases of eye muscle palsies the electromyogram of the affected muscle in connection with the Edrophonium-test is extremely valuable. With regard to modern treatment apart from cholinesterase inhibitors (Pyridostigmine, Neostigmine) thymectomy, the application of corticosteroids, ACTH and especially also immune suppressive drugs (Imurel etc.) is discussed. Of great significance in ocular myasthenia is the local application of cholinesterase inhibitors like Eserine, Prostigmin or Phospholine Iodide.", "contents": "[Diagnosis and treatment of ocular myasthenia (author's transl)]. After discussion of the modern concepts of pathophysiology of ocular myasthenia the ocular symptoms such as ptosis and eye muscle palsies are discussed. As important diagnostic sign the Simpson lid fatigue test before and after application of Tensilon is described. For diagnosis of myasthenic eye muscle palsies electrooculography has a special significance especially in connection with the application of Edrophonium, which normalizes myasthenic hypometric saccades and transforms them even in hypermetric saccades. In doubtful cases of eye muscle palsies the electromyogram of the affected muscle in connection with the Edrophonium-test is extremely valuable. With regard to modern treatment apart from cholinesterase inhibitors (Pyridostigmine, Neostigmine) thymectomy, the application of corticosteroids, ACTH and especially also immune suppressive drugs (Imurel etc.) is discussed. Of great significance in ocular myasthenia is the local application of cholinesterase inhibitors like Eserine, Prostigmin or Phospholine Iodide."}
{"id": "PMID:203743", "title": "[Regulation of the human erythropoietic proliferation pool by the microenvironment (author's transl)].", "content": "The Effects of Various Substances in the Culture Microenvironment on the Proliferation of Erythroblasts in vitro were Studied and Evaluated by differential cell and mitosis counting in normal and pathologic bone marrow. The mitotic frequency and maturation correlated directly with the erythropoietin content of the medium and were potentiated on addition of either folic acid, etiocholanolon or cAMP. However, erythroblast proliferation was stimulated independently of erythropoietin concentration when either cobalt, and androgen or an anabolic substance was added to the medium. An iron-deficient medium prevented the maturation of erythroblasts to reticulocytes, thereby rendering erythropoiesis ineffective. The existence of an erythrocyte chalone ineffective. The existence of an erythrocyte chalone or an erythropoietin inhibitor could not be deduced from our experiments since the transformation of pluripotent to erythropoetin-sensitive stem cells is not included. A stimulation of the granulopoietic proliferation pool occurred when serum from patients with either polycythemia vera or after acute blood loss was added to the medium.", "contents": "[Regulation of the human erythropoietic proliferation pool by the microenvironment (author's transl)]. The Effects of Various Substances in the Culture Microenvironment on the Proliferation of Erythroblasts in vitro were Studied and Evaluated by differential cell and mitosis counting in normal and pathologic bone marrow. The mitotic frequency and maturation correlated directly with the erythropoietin content of the medium and were potentiated on addition of either folic acid, etiocholanolon or cAMP. However, erythroblast proliferation was stimulated independently of erythropoietin concentration when either cobalt, and androgen or an anabolic substance was added to the medium. An iron-deficient medium prevented the maturation of erythroblasts to reticulocytes, thereby rendering erythropoiesis ineffective. The existence of an erythrocyte chalone ineffective. The existence of an erythrocyte chalone or an erythropoietin inhibitor could not be deduced from our experiments since the transformation of pluripotent to erythropoetin-sensitive stem cells is not included. A stimulation of the granulopoietic proliferation pool occurred when serum from patients with either polycythemia vera or after acute blood loss was added to the medium."}
{"id": "PMID:203770", "title": "Pox infection in white rats.", "content": "2 pox outbreaks among white rats in a breeding colony are described. The infection occurred in 3 different forms: pulmonary, dermal and mixed. Apparently healthy animals appeared to be virus carriers. The virus isolated belonged to the genus Orthopoxvirus of Poxviridae family, and was very close to cowpox virus. It differed from reference strains of cowpox virus in having a lower ceiling temperature and a higher pathogenicity for white rats.", "contents": "Pox infection in white rats. 2 pox outbreaks among white rats in a breeding colony are described. The infection occurred in 3 different forms: pulmonary, dermal and mixed. Apparently healthy animals appeared to be virus carriers. The virus isolated belonged to the genus Orthopoxvirus of Poxviridae family, and was very close to cowpox virus. It differed from reference strains of cowpox virus in having a lower ceiling temperature and a higher pathogenicity for white rats."}
{"id": "PMID:203771", "title": "Effects of mercury on lysosomal protein digestion in the kidney proximal tubule.", "content": "The effect of mercury on renal lysosomal protein digestion was studied after administration of mercury in vitro and in vivo. Mercuric chloride or methylmercury chloride was added in vitro to lysosomal enzymes isolated from normal rats, and subsequently, digestion experiments were carried out using 125I-labeled lysozyme or cytochrome c as substrate proteins. Both mercury compounds produced a concentration-dependent inhibition of the degradation of the proteins, mercuric chloride being the strongest inhibitor. Mercuric chloride was also administered to rats in vivo for 5 to 8 months. Renal lysosomal enzymes from these animals also had a decreased ability to digest for the two substrate proteins. Furthermore, the digestion of lysozyme intravenously injected into mercury-intoxicated rats was decreased in renal cortical slices incubated in vitro. Electron microscope autoradiography showed that intravenously injected labeled lysozyme was located primarily over lysosomes in proximal tubule cells 1 hour after injection in both control animals and mercury-intoxicated rats. These results suggest a decreased catabolism of low molecular weight proteins in the kidney during chronic mercury intoxication.", "contents": "Effects of mercury on lysosomal protein digestion in the kidney proximal tubule. The effect of mercury on renal lysosomal protein digestion was studied after administration of mercury in vitro and in vivo. Mercuric chloride or methylmercury chloride was added in vitro to lysosomal enzymes isolated from normal rats, and subsequently, digestion experiments were carried out using 125I-labeled lysozyme or cytochrome c as substrate proteins. Both mercury compounds produced a concentration-dependent inhibition of the degradation of the proteins, mercuric chloride being the strongest inhibitor. Mercuric chloride was also administered to rats in vivo for 5 to 8 months. Renal lysosomal enzymes from these animals also had a decreased ability to digest for the two substrate proteins. Furthermore, the digestion of lysozyme intravenously injected into mercury-intoxicated rats was decreased in renal cortical slices incubated in vitro. Electron microscope autoradiography showed that intravenously injected labeled lysozyme was located primarily over lysosomes in proximal tubule cells 1 hour after injection in both control animals and mercury-intoxicated rats. These results suggest a decreased catabolism of low molecular weight proteins in the kidney during chronic mercury intoxication."}
{"id": "PMID:203775", "title": "Levels of plasma cyclic AMP and insulin in cardiac surgery.", "content": "Cyclic AMP is a common second messenger for a variety of hormones such as catecholamine, glucagon, and growth hormone, which are affected by cardiac surgery. Changes in plasma cyclic AMP level may thus reflect an altered hormonal milieu. The effects of open-heart surgery on plasma cyclic AMP and its relation with serum insulin were studied in 33 adult patients who underwent cardiac surgery with cardiopulmonary bypass. Plasma cyclic AMP levels were markedly elevated during cardiopulmonary bypass and returned toward normal within several days after the operation. The serum insulin concentration remained low, and no positive correlation was found with plasma cyclic AMP level. The responses were similar in patients who had aorta-coronary bypass grafts and those who had valve replacements.", "contents": "Levels of plasma cyclic AMP and insulin in cardiac surgery. Cyclic AMP is a common second messenger for a variety of hormones such as catecholamine, glucagon, and growth hormone, which are affected by cardiac surgery. Changes in plasma cyclic AMP level may thus reflect an altered hormonal milieu. The effects of open-heart surgery on plasma cyclic AMP and its relation with serum insulin were studied in 33 adult patients who underwent cardiac surgery with cardiopulmonary bypass. Plasma cyclic AMP levels were markedly elevated during cardiopulmonary bypass and returned toward normal within several days after the operation. The serum insulin concentration remained low, and no positive correlation was found with plasma cyclic AMP level. The responses were similar in patients who had aorta-coronary bypass grafts and those who had valve replacements."}
{"id": "PMID:203805", "title": "[Fibrous histiocytomas of the nose and paranasal sinuses (author's transl)].", "content": "Fibrous histiocytomas of the nose and paranasal sinuses are very unusual. Two cases of these tumors are reported. Prognostic histological features and biological behaviour are discussed.", "contents": "[Fibrous histiocytomas of the nose and paranasal sinuses (author's transl)]. Fibrous histiocytomas of the nose and paranasal sinuses are very unusual. Two cases of these tumors are reported. Prognostic histological features and biological behaviour are discussed."}
{"id": "PMID:203819", "title": "Visualization of primate high density lipoproteins isolated by density gradient ultracentrifugation.", "content": "High density lipoproteins (HDL) isolated by density gradient ultracentrifugation from the plasma of monkeys ingesting semipurified diets are barely visible. This creates difficulty in separating HDL from other lower density lipoproteins following centrifugation and necessitates collecting lared quantities of background density solution to insure complete recovery of the HDL fraction. A simple procedure is described involving the addition of beta-carotene to nonhuman primate plasma prior to centrifugation which results in the delineation of HDL as a discrete yellow-orange band without affecting certain physical properties of HDL or interfering with standard lipid and protein assays.", "contents": "Visualization of primate high density lipoproteins isolated by density gradient ultracentrifugation. High density lipoproteins (HDL) isolated by density gradient ultracentrifugation from the plasma of monkeys ingesting semipurified diets are barely visible. This creates difficulty in separating HDL from other lower density lipoproteins following centrifugation and necessitates collecting lared quantities of background density solution to insure complete recovery of the HDL fraction. A simple procedure is described involving the addition of beta-carotene to nonhuman primate plasma prior to centrifugation which results in the delineation of HDL as a discrete yellow-orange band without affecting certain physical properties of HDL or interfering with standard lipid and protein assays."}
{"id": "PMID:203822", "title": "[Morphological and histochemical changes in the rat liver in chronic furfural poisoning].", "content": "The experiment was carried out on rats, which were divided into three experimental and one control groups. The experimental animals were intraperitoneally injected with furfural in the dose of 58 mg/kg body weight for 30 days. In the liver samples obtained at autopsy, apart from routine staining with hematoxylin and eosin, estimation of the activity of the following enzymes was made: succinic dehydrogenase. NADH-tetrazol reductase, lactic dehydrogenase, glucose-6-phosphate, adenosine-triphosphatase, Ca-formol, glucose-6-phosphatase and acid phosphatase. Glycogen content was also evaluated. A temporary decrease in the activity of reactions for the enzymes of tissue respiration, an increase in the activity of glucose-6-phosphatase with a simultaneous decrease of glycogen content, activation of intracellular digestive processes, and inhibition of active transport through biological membranes were found in animals intoxicated with furfural.", "contents": "[Morphological and histochemical changes in the rat liver in chronic furfural poisoning]. The experiment was carried out on rats, which were divided into three experimental and one control groups. The experimental animals were intraperitoneally injected with furfural in the dose of 58 mg/kg body weight for 30 days. In the liver samples obtained at autopsy, apart from routine staining with hematoxylin and eosin, estimation of the activity of the following enzymes was made: succinic dehydrogenase. NADH-tetrazol reductase, lactic dehydrogenase, glucose-6-phosphate, adenosine-triphosphatase, Ca-formol, glucose-6-phosphatase and acid phosphatase. Glycogen content was also evaluated. A temporary decrease in the activity of reactions for the enzymes of tissue respiration, an increase in the activity of glucose-6-phosphatase with a simultaneous decrease of glycogen content, activation of intracellular digestive processes, and inhibition of active transport through biological membranes were found in animals intoxicated with furfural."}
{"id": "PMID:203823", "title": "Effect of starvation on hepatic glycogen metabolism and glucose homeostasis.", "content": "The effects of starvation on the hepatic glycogen synthase and phosphporylase systems were sequentially assessed in fed and 24-120-hr-fasted rats. Enzymic changes before and after glucose were correlated with simultaneous measurements of hepatic cyclic AMP and glycogen concentrations and glucose, insulin, and glucagon concentrations in the portal vein plasma. Fasting caused parallel changes in plasma glucose and hepatic glycogen concentrations with decreases by 24 hr and subsequent increases, which correlated with increases in hepatic synthase l and decreases in phosphorylase activites. Hepatic cyclic AMP levels increased as 24-48 hr, decreased below fed levels at 96 hr, and increased again at 120 hr. Fasting caused progressive impairment of glucose disposal, decreased basal and postglucose insulin concentrations, and decreased basal glucagon levels at 48-72 hr. Hepatic synthase l increments following glucose were exaggerated in 48-120-hr-fasted rats, although consistent phosphorylase decrements were seen only in fed rats. There was no clearcut relationship between synthase activation and phosphorylase inactivation following glucose in fed or fasted rats.", "contents": "Effect of starvation on hepatic glycogen metabolism and glucose homeostasis. The effects of starvation on the hepatic glycogen synthase and phosphporylase systems were sequentially assessed in fed and 24-120-hr-fasted rats. Enzymic changes before and after glucose were correlated with simultaneous measurements of hepatic cyclic AMP and glycogen concentrations and glucose, insulin, and glucagon concentrations in the portal vein plasma. Fasting caused parallel changes in plasma glucose and hepatic glycogen concentrations with decreases by 24 hr and subsequent increases, which correlated with increases in hepatic synthase l and decreases in phosphorylase activites. Hepatic cyclic AMP levels increased as 24-48 hr, decreased below fed levels at 96 hr, and increased again at 120 hr. Fasting caused progressive impairment of glucose disposal, decreased basal and postglucose insulin concentrations, and decreased basal glucagon levels at 48-72 hr. Hepatic synthase l increments following glucose were exaggerated in 48-120-hr-fasted rats, although consistent phosphorylase decrements were seen only in fed rats. There was no clearcut relationship between synthase activation and phosphorylase inactivation following glucose in fed or fasted rats."}
{"id": "PMID:203825", "title": "Thermolabile repression of cephalosporinase synthesis in Citrobacter freundii.", "content": "An unusual regulatory system of cephalosporinase synthesis in Citrobacter freundii has been found. When the bacteria are grown at 20 C, the cephalosporinase is synthesized as a typical inducible enzyme and benzylpenicillin acts as an effective inducer. The enzyme, however, is synthesized in the absence of the inducer at growth temperatures above 25 C. when the growth temperature is shifted from 20 C to 37 C, the induction of enzyme synthesis is observed after about one half of the organism doubling time, but it does not occur in the presence of chloramphenicol. The reverse control mutants, the enzyme constitutive synthesis of which is markedly depressed by benzylpenicillin, were isolated from the C. freundii wild strain. The possibility that the enzyme synthesis is governed by a regulatory system analogous to the its mutant of the lac operon in Escherichia coli was suggested.", "contents": "Thermolabile repression of cephalosporinase synthesis in Citrobacter freundii. An unusual regulatory system of cephalosporinase synthesis in Citrobacter freundii has been found. When the bacteria are grown at 20 C, the cephalosporinase is synthesized as a typical inducible enzyme and benzylpenicillin acts as an effective inducer. The enzyme, however, is synthesized in the absence of the inducer at growth temperatures above 25 C. when the growth temperature is shifted from 20 C to 37 C, the induction of enzyme synthesis is observed after about one half of the organism doubling time, but it does not occur in the presence of chloramphenicol. The reverse control mutants, the enzyme constitutive synthesis of which is markedly depressed by benzylpenicillin, were isolated from the C. freundii wild strain. The possibility that the enzyme synthesis is governed by a regulatory system analogous to the its mutant of the lac operon in Escherichia coli was suggested."}
{"id": "PMID:203829", "title": "Rapidly progressive fatal silicosis in a young man.", "content": "A case is reported of rapidly progressive silicosis in a 30-year-old male who developed symptoms two years after first exposure and died 30 months later. The causative agent was silica powder. This case serves to highlight the fact that this potentially dangerous material is currently being used in industry and that adequate precautions are not always taken.", "contents": "Rapidly progressive fatal silicosis in a young man. A case is reported of rapidly progressive silicosis in a 30-year-old male who developed symptoms two years after first exposure and died 30 months later. The causative agent was silica powder. This case serves to highlight the fact that this potentially dangerous material is currently being used in industry and that adequate precautions are not always taken."}
{"id": "PMID:203832", "title": "[Combination or monotherapy of hyperlipoproteinemia typus IIb, IV, V with clofibrate and m-inositolnicotinate or clofibrinic acid (author's transl)].", "content": "Clofibrate and m-Inositolnicotinate in a daily dosage of 1,5 g Clofibrate and 1,2 g m-Inositolnicotinate during long term treatment effected a good triglyceride fall in all three lipoprotein fractions, especially in VLDL. The changing of the hyperlipoproteinemia phenotypus IV to the phenotypus IIb or IIa under monotherapy with Clofibrate or clofibrinic acid could not be avoided by the combination of Clofibrate with m-Inositolnicotinate. Approximately every fourth hyperlipoproteinemia phenotypus IV or V, treated with a combination therapy, had an increase of beta-Cholesterol in the pathological range of more than 210 mg/dl. The combination of Clofibrate with nicotinic acid is not of greater value than the monotherapy with Clofibrate (Atromid S). A combination of Clofibrate and nicotinic acid is useful when pure nicotinic acid (3 to 4g/daily) or its esters, for example m-Inositol-nicotinate (4 to 6g/daily) or beta-Pyridylcarbinol (800 to 1200 mg/daily) are administered in therapeutic doses. With the increased dosage of nicotinic acid, one must expect a large \"drop out\" of these appropriate hyperlipoproteinemia patients because of the side-effects resulting from this particular treatment with nicotinic acid.", "contents": "[Combination or monotherapy of hyperlipoproteinemia typus IIb, IV, V with clofibrate and m-inositolnicotinate or clofibrinic acid (author's transl)]. Clofibrate and m-Inositolnicotinate in a daily dosage of 1,5 g Clofibrate and 1,2 g m-Inositolnicotinate during long term treatment effected a good triglyceride fall in all three lipoprotein fractions, especially in VLDL. The changing of the hyperlipoproteinemia phenotypus IV to the phenotypus IIb or IIa under monotherapy with Clofibrate or clofibrinic acid could not be avoided by the combination of Clofibrate with m-Inositolnicotinate. Approximately every fourth hyperlipoproteinemia phenotypus IV or V, treated with a combination therapy, had an increase of beta-Cholesterol in the pathological range of more than 210 mg/dl. The combination of Clofibrate with nicotinic acid is not of greater value than the monotherapy with Clofibrate (Atromid S). A combination of Clofibrate and nicotinic acid is useful when pure nicotinic acid (3 to 4g/daily) or its esters, for example m-Inositol-nicotinate (4 to 6g/daily) or beta-Pyridylcarbinol (800 to 1200 mg/daily) are administered in therapeutic doses. With the increased dosage of nicotinic acid, one must expect a large \"drop out\" of these appropriate hyperlipoproteinemia patients because of the side-effects resulting from this particular treatment with nicotinic acid."}
{"id": "PMID:203835", "title": "RD cells in the laboratory diagnosis of enteroviruses.", "content": "It is shown that, in addition to the already known replication of Coxsackie A viruses, 16 out of 18 different types of ECHO viruses tested as well as all three types of polioviruses can also be grown in RD cells with the development of a pronounced CPE. One of the exceptions, ECHO virus type 16, can be propagated in either HEL or HFDK cells and the other, ECHO virus type 22, in Vero cells. These four permanent or semi-permanent cell cultures thus prove very useful for the isolation of most of the diagnostically important enteroviruses as well as for their serological identification by neutralization in a micro-titer system described in this paper.", "contents": "RD cells in the laboratory diagnosis of enteroviruses. It is shown that, in addition to the already known replication of Coxsackie A viruses, 16 out of 18 different types of ECHO viruses tested as well as all three types of polioviruses can also be grown in RD cells with the development of a pronounced CPE. One of the exceptions, ECHO virus type 16, can be propagated in either HEL or HFDK cells and the other, ECHO virus type 22, in Vero cells. These four permanent or semi-permanent cell cultures thus prove very useful for the isolation of most of the diagnostically important enteroviruses as well as for their serological identification by neutralization in a micro-titer system described in this paper."}
{"id": "PMID:203847", "title": "[Hepatic disease in childhood and cytomegalovirus infection (author's transl)].", "content": "135 children with hepatitis and 179 patients with hepatomegaly of undetermined etiology were investigated for complement fixing antibodies to cytomegalovirus. 69 patients with hepatitis (51%) and 74 patients with hepatomegaly (41%) had a titer of 1:4 or above as compared with a control group of children without hepatic pathology in whom positive response occurred in only 20 resp. 18%. The mean titer found in the sero-positive patients was also significantly higher than that in the control group. In contrast, the incidence of positive sera in newborns with hyperbilirubinemia of unknown etiology did not differ significantly from that in a healthy control collective. Of 57 patients with liver disease, 20 excreted cytomegalovirus which was isolated 55 times from 103 urine specimens. These patients included 9 with hepatitis and 11 with hepatomegaly. Of 129 children without any indication of liver disease, cytomegalovirus could be demonstrated in only 3. Our results point toward a causal connection between the presence of cytomegalovirus and the development of hepatic disease in childhood.", "contents": "[Hepatic disease in childhood and cytomegalovirus infection (author's transl)]. 135 children with hepatitis and 179 patients with hepatomegaly of undetermined etiology were investigated for complement fixing antibodies to cytomegalovirus. 69 patients with hepatitis (51%) and 74 patients with hepatomegaly (41%) had a titer of 1:4 or above as compared with a control group of children without hepatic pathology in whom positive response occurred in only 20 resp. 18%. The mean titer found in the sero-positive patients was also significantly higher than that in the control group. In contrast, the incidence of positive sera in newborns with hyperbilirubinemia of unknown etiology did not differ significantly from that in a healthy control collective. Of 57 patients with liver disease, 20 excreted cytomegalovirus which was isolated 55 times from 103 urine specimens. These patients included 9 with hepatitis and 11 with hepatomegaly. Of 129 children without any indication of liver disease, cytomegalovirus could be demonstrated in only 3. Our results point toward a causal connection between the presence of cytomegalovirus and the development of hepatic disease in childhood."}
{"id": "PMID:203848", "title": "EMS-induced dominant lethal dose response curve in DBA/1J male mice.", "content": "An ethyl methanesulfonate (EMS) induced dominant lethal dose response experiment was conducted in strain DBA/1J male mice. Two methods of scoring for dominant lethals, the classic method (dissecting females at mid-pregnancy) and an alternative method (inspection of uterine scars after litters were weaned) were compared. Results indicate that strain DBA/1J has a similar sensitivity to EMS-induced dominant lethals as has been previously reported for other mouse genotypes. Of the two methods used to score dominant lethals, the classic method is more sensitive.", "contents": "EMS-induced dominant lethal dose response curve in DBA/1J male mice. An ethyl methanesulfonate (EMS) induced dominant lethal dose response experiment was conducted in strain DBA/1J male mice. Two methods of scoring for dominant lethals, the classic method (dissecting females at mid-pregnancy) and an alternative method (inspection of uterine scars after litters were weaned) were compared. Results indicate that strain DBA/1J has a similar sensitivity to EMS-induced dominant lethals as has been previously reported for other mouse genotypes. Of the two methods used to score dominant lethals, the classic method is more sensitive."}
{"id": "PMID:203849", "title": "Induction of dominant lethals with ethyl methane-sulfonate in male germ cells of mulberry silkwork, Bombyx mori l.", "content": "Sensitivity of male germ cells in the mulberry silkworm, Bombyx mori L., to ethyl methanesulfonate (EMS) was determined by treating newly emerged 5th- instar larvae, and 2-day- and 7-day-old pupae with 3 concentrations, 0.05, 0.1 and 0.15%, of the mutagen. The frequency of dominant-lethal mutations induced by EMS treatment was used as the parameter for the study. Spermatids and spermatozoa were markedly sensitive to EMS. Statistical analysis confirmed that differences in respect of percentage of egg hatch among the 3 different treatments as well as the interactions between the 3 factors, e.g. stages, hatchability and EMS treatment, were highly significant.", "contents": "Induction of dominant lethals with ethyl methane-sulfonate in male germ cells of mulberry silkwork, Bombyx mori l. Sensitivity of male germ cells in the mulberry silkworm, Bombyx mori L., to ethyl methanesulfonate (EMS) was determined by treating newly emerged 5th- instar larvae, and 2-day- and 7-day-old pupae with 3 concentrations, 0.05, 0.1 and 0.15%, of the mutagen. The frequency of dominant-lethal mutations induced by EMS treatment was used as the parameter for the study. Spermatids and spermatozoa were markedly sensitive to EMS. Statistical analysis confirmed that differences in respect of percentage of egg hatch among the 3 different treatments as well as the interactions between the 3 factors, e.g. stages, hatchability and EMS treatment, were highly significant."}
{"id": "PMID:203850", "title": "Inhibition of angiotensin-converting enzyme for diagnosis of renal-artery stenosis.", "content": "To determine its utility as an aid in diagnosis of renovascular hypertension, we administered nonapeptide converting-enzyme inhibitor (CEI) (which inhibits conversion of angiotensin I to angiotensin II) (0.25 mg per kilogram) to 14 unselected hypertensive patients undergoing bilateral renal-vein catheterization. In seven (Group I) predominantly unilateral disease was discovered by angiography (renal-artery stenosis in six and hydronephrosis in one); in the remaining seven (Group II) no rennal-artery abnormality was found. In Group I, mean (+/- S.E.) ratio of involved to uninvolved renal-vein plasma renin activity (PRA) increased from 2.94 +/- 0.91 before to 8.36 +/- 2.94 after CEI (P less than 0.01). In Group II, the ratio (of the initially higher to the lower side) was 1.99 +/- 0.49 before and 1.17 +/- 0.07 after CEI (P greater 0.02). Post-CEI PRA was predicted by pretreatment PRA. Mean blood pressure fell in both groups after CEI, and the decrement was predicted by pre-CEI PRA. These data suggest that CEI can be of use at the time of renal-vein catheterization, serving to increase diagnostic accuracy by increasing the difference in PRA between the two sides when there is unilateral disease.", "contents": "Inhibition of angiotensin-converting enzyme for diagnosis of renal-artery stenosis. To determine its utility as an aid in diagnosis of renovascular hypertension, we administered nonapeptide converting-enzyme inhibitor (CEI) (which inhibits conversion of angiotensin I to angiotensin II) (0.25 mg per kilogram) to 14 unselected hypertensive patients undergoing bilateral renal-vein catheterization. In seven (Group I) predominantly unilateral disease was discovered by angiography (renal-artery stenosis in six and hydronephrosis in one); in the remaining seven (Group II) no rennal-artery abnormality was found. In Group I, mean (+/- S.E.) ratio of involved to uninvolved renal-vein plasma renin activity (PRA) increased from 2.94 +/- 0.91 before to 8.36 +/- 2.94 after CEI (P less than 0.01). In Group II, the ratio (of the initially higher to the lower side) was 1.99 +/- 0.49 before and 1.17 +/- 0.07 after CEI (P greater 0.02). Post-CEI PRA was predicted by pretreatment PRA. Mean blood pressure fell in both groups after CEI, and the decrement was predicted by pre-CEI PRA. These data suggest that CEI can be of use at the time of renal-vein catheterization, serving to increase diagnostic accuracy by increasing the difference in PRA between the two sides when there is unilateral disease."}
{"id": "PMID:203853", "title": "Cushing's disease. Selective trans-sphenoidal resection of pituitary microadenomas.", "content": "We undertook trans-sphenoidal microsurgical pituitary exploration in 20 consecutive patients with Cushing's disease, eight of whom had normal sellar polytomography. Pituitary adenomas were selectively resected in 17 and histologically confirmed in 14. In one patient total hypophysectomy revealed a 1.5-mm basophilic adenoma, and in two patients vascular anomalies prevented sellar exploration. Hypercortisolism was corrected in 17 patients (i.e., in 16 of the 17 undergoing selective tumor removal and in the one with total hypophysectomy). Panhypopituitarism occurred only in this patient, and transient diabetes insipidus occurred in five. Most patients became glucocorticoid deficient and required replacement therapy. We conclude that pituitary tumors are present in the great majority of patient with Cushing's disease, even in the absence of demonstrable tomographic changes in the sella turcica, and that selective removal corrects hypercortisolism with little morbidity.", "contents": "Cushing's disease. Selective trans-sphenoidal resection of pituitary microadenomas. We undertook trans-sphenoidal microsurgical pituitary exploration in 20 consecutive patients with Cushing's disease, eight of whom had normal sellar polytomography. Pituitary adenomas were selectively resected in 17 and histologically confirmed in 14. In one patient total hypophysectomy revealed a 1.5-mm basophilic adenoma, and in two patients vascular anomalies prevented sellar exploration. Hypercortisolism was corrected in 17 patients (i.e., in 16 of the 17 undergoing selective tumor removal and in the one with total hypophysectomy). Panhypopituitarism occurred only in this patient, and transient diabetes insipidus occurred in five. Most patients became glucocorticoid deficient and required replacement therapy. We conclude that pituitary tumors are present in the great majority of patient with Cushing's disease, even in the absence of demonstrable tomographic changes in the sella turcica, and that selective removal corrects hypercortisolism with little morbidity."}
{"id": "PMID:203871", "title": "Differences in pathogenicity and antigenicity among hog cholera virus strains.", "content": "Using antiserum against a particular strain of bovine viral diarrhea virus, the strains of hog cholera virus were divided into two groups, H and B, on the basis of the difference in the degree of neutralization. Group H consisted of strains reacting poorly in neutralization, and group B Consisted of strains reacting well with bovine viral diarrhea antiserum. Most of the strains of group H induced a typical clinical form of hog cholera in experimentally infected pigs. Inoculation of pigs with a strain of group B, however, resulted in a chronic type of illness. When immunized with bovine viral diarrhea virus, pigs succumbed to challenge with group H virus after showing clinical signs of hog cholera, but survived challenge with group B virus without manifesting any clinical sign.", "contents": "Differences in pathogenicity and antigenicity among hog cholera virus strains. Using antiserum against a particular strain of bovine viral diarrhea virus, the strains of hog cholera virus were divided into two groups, H and B, on the basis of the difference in the degree of neutralization. Group H consisted of strains reacting poorly in neutralization, and group B Consisted of strains reacting well with bovine viral diarrhea antiserum. Most of the strains of group H induced a typical clinical form of hog cholera in experimentally infected pigs. Inoculation of pigs with a strain of group B, however, resulted in a chronic type of illness. When immunized with bovine viral diarrhea virus, pigs succumbed to challenge with group H virus after showing clinical signs of hog cholera, but survived challenge with group B virus without manifesting any clinical sign."}
{"id": "PMID:203872", "title": "Pathological changes in chickens inoculated with reticuloendotheliosis-virus-contaminated Marek's disease vaccine.", "content": "A disease characterized by delayed growth, anemia, abnormal feathers, and leg paralysis occurred among chickens inoculated with Marek's disease vaccine over a period from spring to fall in 1974. These chickens were recognized among flocks inoculated with the vaccine produced by two vaccine makers. The affected ones were examined pathologically. Gross examination revealed a slight enlargement of peripheral nerves and atrophy of the spleen, thymus, and bursa of Fabricius. Histopathologically, the peripheral nerves had a mild cell infiltration of lymphoid and plasma cells, edema, degeneration of nerve fibers with Schwann's cell proliferation. Perivascular cuffings consisting mainly of lymphoid cells were seen in the brain and spinal cord. Atrophic changes displayed by prominent reduction of lymphocytes were recognized in the spleen, thymus, and bursa of Fabricius. Etiological examination suggested that most of the chickens examined might have been infected with reticuloendotheliosis virus and not with Marek's disease virus. The pathological changes observed in the peripheral nerves and central nervous system, however, were not distinguishable from those of Marek's disease.", "contents": "Pathological changes in chickens inoculated with reticuloendotheliosis-virus-contaminated Marek's disease vaccine. A disease characterized by delayed growth, anemia, abnormal feathers, and leg paralysis occurred among chickens inoculated with Marek's disease vaccine over a period from spring to fall in 1974. These chickens were recognized among flocks inoculated with the vaccine produced by two vaccine makers. The affected ones were examined pathologically. Gross examination revealed a slight enlargement of peripheral nerves and atrophy of the spleen, thymus, and bursa of Fabricius. Histopathologically, the peripheral nerves had a mild cell infiltration of lymphoid and plasma cells, edema, degeneration of nerve fibers with Schwann's cell proliferation. Perivascular cuffings consisting mainly of lymphoid cells were seen in the brain and spinal cord. Atrophic changes displayed by prominent reduction of lymphocytes were recognized in the spleen, thymus, and bursa of Fabricius. Etiological examination suggested that most of the chickens examined might have been infected with reticuloendotheliosis virus and not with Marek's disease virus. The pathological changes observed in the peripheral nerves and central nervous system, however, were not distinguishable from those of Marek's disease."}
{"id": "PMID:203875", "title": "Somatosensory-evoked potentials elecited by bilateral stimulation of the median nerve and its clinical application.", "content": "Somatosensory evoked potentials (SEPs) elicited by bilaterally simultaneous median nerve stimulation (BS) were studied in 28 normal subjects and in 20 patients with various cerebral lesions. In normals, SEP'S evoked by BS were symmetric between the homologous areas of the two hemispheres and resembled the response contralateral to unilateral stimulation (US). In patients with a cerebral lesion, BS responses were not only asymmetric but often differed in wave form from the response of the affected hemisphere to contralateral US. These alterations were attributed to the cumulative interactions of the anomalous contralateral and ipsilateral components. The additional use of BS made it possible to demonstrate SEP abnormalities that might have been regarded as normal or equivocal if only the US method had been used. The neurophysiologic mechanisms of the origin of SEP are discussed.", "contents": "Somatosensory-evoked potentials elecited by bilateral stimulation of the median nerve and its clinical application. Somatosensory evoked potentials (SEPs) elicited by bilaterally simultaneous median nerve stimulation (BS) were studied in 28 normal subjects and in 20 patients with various cerebral lesions. In normals, SEP'S evoked by BS were symmetric between the homologous areas of the two hemispheres and resembled the response contralateral to unilateral stimulation (US). In patients with a cerebral lesion, BS responses were not only asymmetric but often differed in wave form from the response of the affected hemisphere to contralateral US. These alterations were attributed to the cumulative interactions of the anomalous contralateral and ipsilateral components. The additional use of BS made it possible to demonstrate SEP abnormalities that might have been regarded as normal or equivocal if only the US method had been used. The neurophysiologic mechanisms of the origin of SEP are discussed."}
{"id": "PMID:203876", "title": "Serum antibodies to cytomegalovirus in myasthenia gravis: effects of thymectomy and steroids.", "content": "The etiology of the immunologic abnormalities in myasthenia gravis (MG) remains unknown. Evidence for persistent viral infection was sought by determining serum antibody titers to several enveloped RNA and DNA viruses. Compared to healthy controls matched for age, sex, geography and socioeconomic status, patients with MG were more likely to have elevated titers of complement-fixing antibody to cytomegalovirus (CMV). Patients with MG not treated with thymectomy or steroids had elevated CMV titers, whereas thymectomized or steroid-treated patients did not; the differences were statistically significant (p less than 0.01). These results are consistent with the hypothesis that there is persistent viral antigenic stimulation in the myasthenic thymus, arising from viral protein incorporation into epithelioid-myoid cell surface membranes and subsequent induction of an antibody to these acetylcholine receptor (AChR)-bearing thymic cells. This antibody then cross-reacts with AChR at the neuromuscular junction.", "contents": "Serum antibodies to cytomegalovirus in myasthenia gravis: effects of thymectomy and steroids. The etiology of the immunologic abnormalities in myasthenia gravis (MG) remains unknown. Evidence for persistent viral infection was sought by determining serum antibody titers to several enveloped RNA and DNA viruses. Compared to healthy controls matched for age, sex, geography and socioeconomic status, patients with MG were more likely to have elevated titers of complement-fixing antibody to cytomegalovirus (CMV). Patients with MG not treated with thymectomy or steroids had elevated CMV titers, whereas thymectomized or steroid-treated patients did not; the differences were statistically significant (p less than 0.01). These results are consistent with the hypothesis that there is persistent viral antigenic stimulation in the myasthenic thymus, arising from viral protein incorporation into epithelioid-myoid cell surface membranes and subsequent induction of an antibody to these acetylcholine receptor (AChR)-bearing thymic cells. This antibody then cross-reacts with AChR at the neuromuscular junction."}
{"id": "PMID:203879", "title": "Metastatic oat cell carcinoma simulating liver cirrhosis.", "content": "A case of oat cell bronchial carcinoma that clinically simulated liver cirrhosis is reported. Post mortem findings included the very unusual intrasinusoidal pattern of liver metastases.", "contents": "Metastatic oat cell carcinoma simulating liver cirrhosis. A case of oat cell bronchial carcinoma that clinically simulated liver cirrhosis is reported. Post mortem findings included the very unusual intrasinusoidal pattern of liver metastases."}
{"id": "PMID:203880", "title": "Effects of ritodrine and isoxsuprine with and without dexamethasone during late pregnancy.", "content": "beta-Adrenergic agents are used to inhibit preterm labor and glucocorticoids to accelerate fetal pulmonary maturation. A study was designed to investigate the metabolic effects of intravenous infusion of ritodrine (150 to 100 microgram/min) or isoxsuprine (200 to 150 microgram/min) in a series of 28 patients with gestations of 28 to 40 weeks, with and without concomitant dexamethasone therapy. Ritodrine was more potent than isoxsuprine in increasing the circulating levels of cyclic AMP, glucose, insulin, and triglycerides. The diabetogenic effect of both ritodrine and isoxsuprine was so slight that it did not have any clinical significance in women with normal glucose tolerance. The results were similar when these beta-adrenergic tocolytics were given to women concomitantly with intramuscular dexamethasone therapy, although dexamethasone appeared to minimally impair carbohydrate metabolism. Both ritodrine and isoxsuprine caused a significant fall in serum iron and potassium, and this effect was unaltered by dexamethasone. Serial serum potassium levels should be obtained during long-term infusion of beta-mimetics.", "contents": "Effects of ritodrine and isoxsuprine with and without dexamethasone during late pregnancy. beta-Adrenergic agents are used to inhibit preterm labor and glucocorticoids to accelerate fetal pulmonary maturation. A study was designed to investigate the metabolic effects of intravenous infusion of ritodrine (150 to 100 microgram/min) or isoxsuprine (200 to 150 microgram/min) in a series of 28 patients with gestations of 28 to 40 weeks, with and without concomitant dexamethasone therapy. Ritodrine was more potent than isoxsuprine in increasing the circulating levels of cyclic AMP, glucose, insulin, and triglycerides. The diabetogenic effect of both ritodrine and isoxsuprine was so slight that it did not have any clinical significance in women with normal glucose tolerance. The results were similar when these beta-adrenergic tocolytics were given to women concomitantly with intramuscular dexamethasone therapy, although dexamethasone appeared to minimally impair carbohydrate metabolism. Both ritodrine and isoxsuprine caused a significant fall in serum iron and potassium, and this effect was unaltered by dexamethasone. Serial serum potassium levels should be obtained during long-term infusion of beta-mimetics."}
{"id": "PMID:203881", "title": "Arrhenoblastoma during pregnancy.", "content": "Arrhenoblastoma is a rare complication of pregnancy. A case of fatal nonvirilizing arrhenoblastoma in a pregnant adolescent, the third such case to appear in the literature, is discussed. Fifteen cases of arrhenoblastoma in pregnancy that have appeared in the recent literature are reviewed; 87% of these tumors were virilizing. When virilization is absent the diagnosis is difficult. Among the more common presenting symptoms are weight loss, nausea and vomiting, abdominal pain, and a palpable abdominal mass. Arrhenoblastoma occurring during pregnancy has a 31% maternal mortality, 44% rate of malignancy, and a 50% perinatal mortality.", "contents": "Arrhenoblastoma during pregnancy. Arrhenoblastoma is a rare complication of pregnancy. A case of fatal nonvirilizing arrhenoblastoma in a pregnant adolescent, the third such case to appear in the literature, is discussed. Fifteen cases of arrhenoblastoma in pregnancy that have appeared in the recent literature are reviewed; 87% of these tumors were virilizing. When virilization is absent the diagnosis is difficult. Among the more common presenting symptoms are weight loss, nausea and vomiting, abdominal pain, and a palpable abdominal mass. Arrhenoblastoma occurring during pregnancy has a 31% maternal mortality, 44% rate of malignancy, and a 50% perinatal mortality."}
{"id": "PMID:203884", "title": "Therapy of small cell carcinoma of the lung with hexamethylmelamine.", "content": "Hexamethylmelamine (HXM) is one of the substituted melamines derived from cyanuric chloride [1]. Previous studies with HXM have shown activity against small cell carcinoma of the lung, when it was given as a single agent [2, 3]. Because of relatively mild bone marrow toxicity, HXM was subsequently given in combination with other drugs and/or radiation therapy, in order to improve the therapeutic results. In this paper, our experience with HXM in treatment of small cell carcinoma of the lung is summarised.", "contents": "Therapy of small cell carcinoma of the lung with hexamethylmelamine. Hexamethylmelamine (HXM) is one of the substituted melamines derived from cyanuric chloride [1]. Previous studies with HXM have shown activity against small cell carcinoma of the lung, when it was given as a single agent [2, 3]. Because of relatively mild bone marrow toxicity, HXM was subsequently given in combination with other drugs and/or radiation therapy, in order to improve the therapeutic results. In this paper, our experience with HXM in treatment of small cell carcinoma of the lung is summarised."}
{"id": "PMID:203885", "title": "Methyl (5-(2-thienylcarbonyl)-1H-benzimidazole-2-yl) carbamate, (R17934), a synthetic microtubule inhibitor, prevents malignant invasion in vitro.", "content": "The effect of malignant invasion of methyl (5-(2-thienylcarbonyl)-1H-benzimidazole-2-yl) carbamate, (R17934), a microtubule inhibitor, was examined in organotypical co-cultures of mouse sarcoma virus transformed cells (MO4) and embryonic chick tissues. In contrast with control cultures, 1 microgram/ml R17934 prevented invasion of MO4 cells into the host tissue. Since mitostatic doses of 5-fluorouracil did not inhibit invasion, we presumed that the anti-invasive properties of R17934 were correlated with a loss of microtubule mediated directional cell migration.", "contents": "Methyl (5-(2-thienylcarbonyl)-1H-benzimidazole-2-yl) carbamate, (R17934), a synthetic microtubule inhibitor, prevents malignant invasion in vitro. The effect of malignant invasion of methyl (5-(2-thienylcarbonyl)-1H-benzimidazole-2-yl) carbamate, (R17934), a microtubule inhibitor, was examined in organotypical co-cultures of mouse sarcoma virus transformed cells (MO4) and embryonic chick tissues. In contrast with control cultures, 1 microgram/ml R17934 prevented invasion of MO4 cells into the host tissue. Since mitostatic doses of 5-fluorouracil did not inhibit invasion, we presumed that the anti-invasive properties of R17934 were correlated with a loss of microtubule mediated directional cell migration."}
{"id": "PMID:203887", "title": "[Effect of adrenocorticotropic hormone on nucleic acid and protein synthesis and content in the brain of rat embryos in the early stages of neurogenesis].", "content": "The injection of adrenocorticotropic hormone (ACTH) of prolonged effect at the doses of 4 and 10 M. U. to the intact rats from the 11th till the 15th day of pregnancy resulted in the twofold increase of protein content in the brain and its decrease in the liver of 15 days old embryos, as compared with the control ones. The content of DNA, RNA and proteins in the placenta of experimental animals increased as well. The rate of incorporation of 3H-thymidine in the liver DNA and 14C-leucine in the liver and brain acid-soluble protein decreased within small intervals of time following the treatment. The total radioactivity of proteins in the liver, brain and placenta calculated per DNA unit was similar to the control one whereas the specific radioactivity of total protein in the liver of experimental embryos was higher than in the control.", "contents": "[Effect of adrenocorticotropic hormone on nucleic acid and protein synthesis and content in the brain of rat embryos in the early stages of neurogenesis]. The injection of adrenocorticotropic hormone (ACTH) of prolonged effect at the doses of 4 and 10 M. U. to the intact rats from the 11th till the 15th day of pregnancy resulted in the twofold increase of protein content in the brain and its decrease in the liver of 15 days old embryos, as compared with the control ones. The content of DNA, RNA and proteins in the placenta of experimental animals increased as well. The rate of incorporation of 3H-thymidine in the liver DNA and 14C-leucine in the liver and brain acid-soluble protein decreased within small intervals of time following the treatment. The total radioactivity of proteins in the liver, brain and placenta calculated per DNA unit was similar to the control one whereas the specific radioactivity of total protein in the liver of experimental embryos was higher than in the control."}
{"id": "PMID:203897", "title": "[A study of pancreatic insulinomas by electron microscopy. 9 cases (author's transl)].", "content": "Nine hypoglycaemia-inducing pancreatic tumours were studied by electron microscopy. In 8 of these tumours, it was possible to identify, within the cell cytoplasm, secretory granules with a \"paracrystalline\" content, identical in appearance to the granules of the B cell of the normal human pancreas. Thus electron microscopy would appear to be a reliable and sensitive method for the morphological identification of these endocrine tumours of the pancreas.", "contents": "[A study of pancreatic insulinomas by electron microscopy. 9 cases (author's transl)]. Nine hypoglycaemia-inducing pancreatic tumours were studied by electron microscopy. In 8 of these tumours, it was possible to identify, within the cell cytoplasm, secretory granules with a \"paracrystalline\" content, identical in appearance to the granules of the B cell of the normal human pancreas. Thus electron microscopy would appear to be a reliable and sensitive method for the morphological identification of these endocrine tumours of the pancreas."}
{"id": "PMID:203902", "title": "Lung cancer: the pathologist's role in management.", "content": "The prognosis of lung cancer is poor, although there is hope for improvement based on early detection through cytologic screening and the use of newer treatment protocols. Although there are difficulties inherent in classifying tumors by type on the basis of very small samples of lesions that are not necessarily homogeneous, the pathologist should use a standard classification that sets forth definite criteria for the differentiated types. Among the common tumors, a small, well-differentiated epidermoid carcinoma with no evidence of lymph node involvement has the most favorable prognosis, and a small-cell anaplastic or oat cell carcinoma the worst. Results of therapy for tumors of other types show much variation. Future studies of lung cancer should include careful clinical staging and, when resection is done, pathologic staging. More study of the immunomorphology of lymph nodes is needed, as this may provide highly useful prognostic information.", "contents": "Lung cancer: the pathologist's role in management. The prognosis of lung cancer is poor, although there is hope for improvement based on early detection through cytologic screening and the use of newer treatment protocols. Although there are difficulties inherent in classifying tumors by type on the basis of very small samples of lesions that are not necessarily homogeneous, the pathologist should use a standard classification that sets forth definite criteria for the differentiated types. Among the common tumors, a small, well-differentiated epidermoid carcinoma with no evidence of lymph node involvement has the most favorable prognosis, and a small-cell anaplastic or oat cell carcinoma the worst. Results of therapy for tumors of other types show much variation. Future studies of lung cancer should include careful clinical staging and, when resection is done, pathologic staging. More study of the immunomorphology of lymph nodes is needed, as this may provide highly useful prognostic information."}
{"id": "PMID:203903", "title": "Extrapulmonary manifestations of tumors of the lung.", "content": "Lung tumors, among other, secrete substances which are identical to or which mimic the activities of conventional hormones. These ectopic tumor secretions appear to be anarchistic and beyond the control of mechanisms regulating normal endocrine physiology. Despite the relative inefficiency of these tumors as endocrine organs, production of sufficient quantities of the substance, exceeding those from normal sources, results in recognizable ectopic endocrinopathies. The association of certain tumor cell types with specific hormonal patterns (Cushing syndrome with oat cell; hypercalcemia with squamous cell) is considered consistent with the concept of genetic derepression.", "contents": "Extrapulmonary manifestations of tumors of the lung. Lung tumors, among other, secrete substances which are identical to or which mimic the activities of conventional hormones. These ectopic tumor secretions appear to be anarchistic and beyond the control of mechanisms regulating normal endocrine physiology. Despite the relative inefficiency of these tumors as endocrine organs, production of sufficient quantities of the substance, exceeding those from normal sources, results in recognizable ectopic endocrinopathies. The association of certain tumor cell types with specific hormonal patterns (Cushing syndrome with oat cell; hypercalcemia with squamous cell) is considered consistent with the concept of genetic derepression."}
{"id": "PMID:203904", "title": "Benign and malignant liver neoplasms: some new etiologic associations.", "content": "Several agents have recently been implicated in the development of benign and malignant liver neoplasms. Recognition of their possible role by the primary care physician may prevent serious consequences to patients exposed to these agents, which include oral contraceptives, androgens, hepatitis virus, and vinyl chloride.", "contents": "Benign and malignant liver neoplasms: some new etiologic associations. Several agents have recently been implicated in the development of benign and malignant liver neoplasms. Recognition of their possible role by the primary care physician may prevent serious consequences to patients exposed to these agents, which include oral contraceptives, androgens, hepatitis virus, and vinyl chloride."}
{"id": "PMID:203906", "title": "Perianal Paget's disease.", "content": "Paget's disease involves the ducts of apocrine glands and the overlying epidermis and is considered to be locally neoplastic. It is capable of developing into invasive carcinoma and in this event the prognosis is poor. The perianal skin may be affected by Paget's disease. This is a rare disorder and the four patients who have been seen with this disease at St Mark's Hospital since 1930 are described.", "contents": "Perianal Paget's disease. Paget's disease involves the ducts of apocrine glands and the overlying epidermis and is considered to be locally neoplastic. It is capable of developing into invasive carcinoma and in this event the prognosis is poor. The perianal skin may be affected by Paget's disease. This is a rare disorder and the four patients who have been seen with this disease at St Mark's Hospital since 1930 are described."}
{"id": "PMID:203907", "title": "Effect of infectious bursal disease on the severity of Eimeria tenella infections in broiler chicks.", "content": "A study was initiated to determine whether prior exposure to infectious bursal disease virus (IBDV) influenced the susceptibility of young broiler chicks to Eimeria tentella infections. When one-day-old chicks infected with IBDV were subsequently challenged with E. tenella at 7 days of age, they suffered significantly higher mortality and lesion scores than their hatchmates which were not exposed to IBDV. Initial exposure to IBDV also had an effect on the development of E. tenella induced hemorrhaging. Hemorrhaging commenced late on the third day following E. tenella inoculation in chicks infected with both IBDV and E. tenella, while bleeding did not occur in the E. tenella alone group until late on the fourth day post-coccidial challenge. No significant differences in weight gains at 7 or 14 days after E. tenella infection were observed between chicks receiving the double infection and those given only E. tenella.", "contents": "Effect of infectious bursal disease on the severity of Eimeria tenella infections in broiler chicks. A study was initiated to determine whether prior exposure to infectious bursal disease virus (IBDV) influenced the susceptibility of young broiler chicks to Eimeria tentella infections. When one-day-old chicks infected with IBDV were subsequently challenged with E. tenella at 7 days of age, they suffered significantly higher mortality and lesion scores than their hatchmates which were not exposed to IBDV. Initial exposure to IBDV also had an effect on the development of E. tenella induced hemorrhaging. Hemorrhaging commenced late on the third day following E. tenella inoculation in chicks infected with both IBDV and E. tenella, while bleeding did not occur in the E. tenella alone group until late on the fourth day post-coccidial challenge. No significant differences in weight gains at 7 or 14 days after E. tenella infection were observed between chicks receiving the double infection and those given only E. tenella."}
{"id": "PMID:203908", "title": "The turnover rate of lipoprotein of d less than 1.006 from plasma of laying turkey hens.", "content": "The turnover rate of plasma \"lower density fraction\" (LDF, d less than 1.006) lipoprotein was determined in two laying turkey hens. LDF was labeled by injecting 1-14C-palmitate which was incorporated into the triglyceride (TG) of circulating LDF. The turnover rates were determined from concentration and half life (t1/2) of the ultracentrifugally-isolated LDF. These values were 22 mu equiv. of TG fatty acid (TGFA) per ml. plasma and 431 min. The turnover rate of LDF was 17.57 mili equiv. TGFA/day or 5.0 g. of TGFA/day as sterate. It was estimated that 3.2 g. of LDF-TGFA/day were removed as egg yolk.", "contents": "The turnover rate of lipoprotein of d less than 1.006 from plasma of laying turkey hens. The turnover rate of plasma \"lower density fraction\" (LDF, d less than 1.006) lipoprotein was determined in two laying turkey hens. LDF was labeled by injecting 1-14C-palmitate which was incorporated into the triglyceride (TG) of circulating LDF. The turnover rates were determined from concentration and half life (t1/2) of the ultracentrifugally-isolated LDF. These values were 22 mu equiv. of TG fatty acid (TGFA) per ml. plasma and 431 min. The turnover rate of LDF was 17.57 mili equiv. TGFA/day or 5.0 g. of TGFA/day as sterate. It was estimated that 3.2 g. of LDF-TGFA/day were removed as egg yolk."}
{"id": "PMID:203909", "title": "The influence of crude cottonseed oil in the feed on the blood and egg yolk lipoproteins of laying hens.", "content": "Lipovitellin, very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), and proteins of d greater than 1.20 were isolated from blood plasma and egg yolks obtained from hens fed a normal diet or one containing 2.5% of crude cottonseed oil. The amounts and compositions of each fraction were determined. Hen blood plasma and egg yolk VLDL and LDL obtained from hens fed a normal diet contained similar levels of lipid, and the fatty acid compositions of those lipids were, for the most part, similar. The percentages of VLDL and LDL in total lipoproteins were similar for plasma and egg yolk obtained from hens fed the normal diet. Separation of VLDL from LDL was not clear-cut in eggs from hens fed the diet which contained crude cottonseed oil. Lipovitellin, as it is isolated from egg yolk, did not appear to be present in any appreciable amount in hen blood plasma. Hen plasma appeared to contain about 10% of a liproprotein d greater than 1.20, the lipid of which was similar in fatty acid composition to that of lipovitellin except for palmitic and oleic acids. Lipids of all the different lipoproteins isolated from plasma and egg yolks of hens fed diets which contained 2.5% of crude cottonseed oil contained more stearic acid and less palmitoleic and oleic acids than did those from normal hens. The increased content of stearic acid increased the density of the lipoproteins so that a larger proportion of the lipoproteins were in the LDL and a smaller proportion were in the VLDL than in lipoproteins from normal plasma and eggs.", "contents": "The influence of crude cottonseed oil in the feed on the blood and egg yolk lipoproteins of laying hens. Lipovitellin, very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), and proteins of d greater than 1.20 were isolated from blood plasma and egg yolks obtained from hens fed a normal diet or one containing 2.5% of crude cottonseed oil. The amounts and compositions of each fraction were determined. Hen blood plasma and egg yolk VLDL and LDL obtained from hens fed a normal diet contained similar levels of lipid, and the fatty acid compositions of those lipids were, for the most part, similar. The percentages of VLDL and LDL in total lipoproteins were similar for plasma and egg yolk obtained from hens fed the normal diet. Separation of VLDL from LDL was not clear-cut in eggs from hens fed the diet which contained crude cottonseed oil. Lipovitellin, as it is isolated from egg yolk, did not appear to be present in any appreciable amount in hen blood plasma. Hen plasma appeared to contain about 10% of a liproprotein d greater than 1.20, the lipid of which was similar in fatty acid composition to that of lipovitellin except for palmitic and oleic acids. Lipids of all the different lipoproteins isolated from plasma and egg yolks of hens fed diets which contained 2.5% of crude cottonseed oil contained more stearic acid and less palmitoleic and oleic acids than did those from normal hens. The increased content of stearic acid increased the density of the lipoproteins so that a larger proportion of the lipoproteins were in the LDL and a smaller proportion were in the VLDL than in lipoproteins from normal plasma and eggs."}
{"id": "PMID:203911", "title": "Interrelationship of dietary vitamin D3 with zinc and iron in young turkeys.", "content": "Three experiments were conducted with Large White turkeys to four weeks of age. The interrelationship of zinc and vitamin D3 was studied in two experiments. Iron and vitamin D3 were involved in one experiment. One group of ten male and one group of ten female poults were randomly assigned to each treatment within an experiment. All experiments involved a factorial arrangement of two dietary variables, D3 and either zinc or iron. For example, all possible combinations of four zinc levels; 31, 46, 76 and 106 p.p.m. and three vitamin D3 levels; 600, 1200, and 3600 I.C. units/kg. were fed in the second zinc experiment. Significant (P less than 0.05) weight gain differences occurred among both zinc and D3 levels in this experiment. Four week body weights were 356, 436, 459 and 444 g., respectively, for Zn levels; and 409, 410 and 452 g., respectively, for D3 levels. Significant (P less than 0.05) interactions occurred between dietary zinc and D3 levels, and between iron and D3 levels relative to body weight gain, Vitamin D3 tended to increase tibia zinc levels in poults receiving higher zinc levels; the opposite occurred with lower levels of the element. Zinc level in feces was decreased with vitamin D3. Hemoglobin level was not influenced by D3 but was increased by iron.", "contents": "Interrelationship of dietary vitamin D3 with zinc and iron in young turkeys. Three experiments were conducted with Large White turkeys to four weeks of age. The interrelationship of zinc and vitamin D3 was studied in two experiments. Iron and vitamin D3 were involved in one experiment. One group of ten male and one group of ten female poults were randomly assigned to each treatment within an experiment. All experiments involved a factorial arrangement of two dietary variables, D3 and either zinc or iron. For example, all possible combinations of four zinc levels; 31, 46, 76 and 106 p.p.m. and three vitamin D3 levels; 600, 1200, and 3600 I.C. units/kg. were fed in the second zinc experiment. Significant (P less than 0.05) weight gain differences occurred among both zinc and D3 levels in this experiment. Four week body weights were 356, 436, 459 and 444 g., respectively, for Zn levels; and 409, 410 and 452 g., respectively, for D3 levels. Significant (P less than 0.05) interactions occurred between dietary zinc and D3 levels, and between iron and D3 levels relative to body weight gain, Vitamin D3 tended to increase tibia zinc levels in poults receiving higher zinc levels; the opposite occurred with lower levels of the element. Zinc level in feces was decreased with vitamin D3. Hemoglobin level was not influenced by D3 but was increased by iron."}
{"id": "PMID:203913", "title": "Genetic resistance to lymphoid tumor transplants.", "content": "Day-old chicks of Ottawa strains 4 and 5 and Cornell strains K and S, with or without maternal antibody against antigens related to Marek's disease (MD), were challenged with serial dilutions of MD tumor transplants (JMV-L or JMV-H) or transmissible lymphoid tumor (TLT) of Olson in three consecutive experiments. Thirty chicks were tested in most combinations of strain, dilution and antibody status for a total of approximately 2000 chicks per experiment. Two subsequent experiments, with a total of more than 1900 chickens, investigated the influence of age at challenge on the resistance of strains 4, K and S to JMV-L and the objective of the sixth experiment was to determine the chromosomal sex of the tumor cells. In terms of mortality up to 16 or 17 days after inoculation, the response to challenge of day-old chicks with JMV-L did not appear to be influenced by the presence of antibody against MD related antigens but differed among strains of chickens. The estimated dose (LD50) that would kill 50% of a challenged population of Strain 4 was approximately 10,000 live JMV-L cells, while the corresponding estimates for strains 5 and K were approximately 600 cells and for strain S it was 50 cells. JMV-H and TLT were highly lethal to all four strains and all estimates of LD50 at 16 or 17 days post challenge were less than 10 cells. Resistance to JMV-L increased rapidly with age at challenge. Strains 4 and K were approaching complete resistance by 7 days of age and the susceptible strain S, when challenged at 14 days, was more resistant than day-old chicks of strains 4 and K. The chromosomal sex of the JMV-L, JMV-H and TLT tumor cells was female and this marker was used to confirm their transplantability.", "contents": "Genetic resistance to lymphoid tumor transplants. Day-old chicks of Ottawa strains 4 and 5 and Cornell strains K and S, with or without maternal antibody against antigens related to Marek's disease (MD), were challenged with serial dilutions of MD tumor transplants (JMV-L or JMV-H) or transmissible lymphoid tumor (TLT) of Olson in three consecutive experiments. Thirty chicks were tested in most combinations of strain, dilution and antibody status for a total of approximately 2000 chicks per experiment. Two subsequent experiments, with a total of more than 1900 chickens, investigated the influence of age at challenge on the resistance of strains 4, K and S to JMV-L and the objective of the sixth experiment was to determine the chromosomal sex of the tumor cells. In terms of mortality up to 16 or 17 days after inoculation, the response to challenge of day-old chicks with JMV-L did not appear to be influenced by the presence of antibody against MD related antigens but differed among strains of chickens. The estimated dose (LD50) that would kill 50% of a challenged population of Strain 4 was approximately 10,000 live JMV-L cells, while the corresponding estimates for strains 5 and K were approximately 600 cells and for strain S it was 50 cells. JMV-H and TLT were highly lethal to all four strains and all estimates of LD50 at 16 or 17 days post challenge were less than 10 cells. Resistance to JMV-L increased rapidly with age at challenge. Strains 4 and K were approaching complete resistance by 7 days of age and the susceptible strain S, when challenged at 14 days, was more resistant than day-old chicks of strains 4 and K. The chromosomal sex of the JMV-L, JMV-H and TLT tumor cells was female and this marker was used to confirm their transplantability."}
{"id": "PMID:203914", "title": "Effect of polychlorinated biphenyls (Aroclor 1254) on liver gluconeogenic enzyme activities in embryonic and growing chickens.", "content": "Fertile Nick Chick eggs were injected with 0.05, 0.1, 0.5 and 5 p.p.m. of PCB (Aroclor 1254) on day zero and were incubated until the 14th day of incubation. Nick Chick cockerels, one day old, were fed different levels of PCB in their diet for two weeks. The levels of PCB used were 0.1, 1, 5, 100 and 200 p.p.m. Key gluconeogenic enzyme activities were measured in the liver of both experimental groups. In the liver of chick embryos and growing chickens the decrease of the activity of all key gluconeogenic enzymes, with the exception of G6P-ase in embyronic liver, and FDP-ase in that of growing chickens, was estimated. The inhibited gluconeogenesis may account for the embryonic death in eggs contaminated with PCB's.", "contents": "Effect of polychlorinated biphenyls (Aroclor 1254) on liver gluconeogenic enzyme activities in embryonic and growing chickens. Fertile Nick Chick eggs were injected with 0.05, 0.1, 0.5 and 5 p.p.m. of PCB (Aroclor 1254) on day zero and were incubated until the 14th day of incubation. Nick Chick cockerels, one day old, were fed different levels of PCB in their diet for two weeks. The levels of PCB used were 0.1, 1, 5, 100 and 200 p.p.m. Key gluconeogenic enzyme activities were measured in the liver of both experimental groups. In the liver of chick embryos and growing chickens the decrease of the activity of all key gluconeogenic enzymes, with the exception of G6P-ase in embyronic liver, and FDP-ase in that of growing chickens, was estimated. The inhibited gluconeogenesis may account for the embryonic death in eggs contaminated with PCB's."}
{"id": "PMID:203915", "title": "Immune response in progressor and regressor strains of chickens at specific intervals after a primary challenge with Rous sarcoma virus.", "content": "A progressor line and a regressor line of chickens were compared for development of immune response, after an initial inoculation of Rous sarcoma virus in the wing-web. Quantitative measures of immunity were determined for the two contrasting lines of chickens at specific intervals after the initial challenge. It was found that subsequent challenges, with either Rous sarcoma virus or tumor homogenate, in the opposite wing-web were met by an early immune response from the regressor line. This early response was absent in the progressor line. However, both lines showed a similar immune response after a time interval of 15 days from the initial challenge. The genes for regression exert this early immune response which is the key to spontaneous regression of Rous sarcomas.", "contents": "Immune response in progressor and regressor strains of chickens at specific intervals after a primary challenge with Rous sarcoma virus. A progressor line and a regressor line of chickens were compared for development of immune response, after an initial inoculation of Rous sarcoma virus in the wing-web. Quantitative measures of immunity were determined for the two contrasting lines of chickens at specific intervals after the initial challenge. It was found that subsequent challenges, with either Rous sarcoma virus or tumor homogenate, in the opposite wing-web were met by an early immune response from the regressor line. This early response was absent in the progressor line. However, both lines showed a similar immune response after a time interval of 15 days from the initial challenge. The genes for regression exert this early immune response which is the key to spontaneous regression of Rous sarcomas."}
{"id": "PMID:203916", "title": "Comparison of tracheal histopathology and scanning electron microscopy of infectious laryngotracheitis.", "content": "Samples of trachea were examined with light microscope, fluorescent microscope, and scanning electron microscopy (SEM). Negative controls and infectious laryngotracheitis (ILT) positive samples were compared. Histopathology illustrated lesions characteristic fo ILT. Lesions seen with SEM suggested surface changes including ciliary disruption. luminal debris, epithelial slough, crevices, hemorrhage and exudate. Fluorescence was noted in infected tracheas throughout both trials using fluorescent antibody (FA) technique.", "contents": "Comparison of tracheal histopathology and scanning electron microscopy of infectious laryngotracheitis. Samples of trachea were examined with light microscope, fluorescent microscope, and scanning electron microscopy (SEM). Negative controls and infectious laryngotracheitis (ILT) positive samples were compared. Histopathology illustrated lesions characteristic fo ILT. Lesions seen with SEM suggested surface changes including ciliary disruption. luminal debris, epithelial slough, crevices, hemorrhage and exudate. Fluorescence was noted in infected tracheas throughout both trials using fluorescent antibody (FA) technique."}
{"id": "PMID:203917", "title": "Age-influence variations in the levels of cholesterol and ATPase activity in the testes of prepuberal chicks.", "content": "Changes in the levels of total, free and esterified cholesterol and ATPase activity were measured in male prepuberal Nigerian fowl. Results showed that in all cases, the testicular levels of these parameters increased to peak levels and decreased thereafter. Total and free cholesterol levels were maximal at 12 weeks while the esterification of cholesterol was maintained from 14 weeks through to the 16th week. The results of ATPase activity corroborated these findings. The data suggest that peak androgen formation occurred in these chicks between 14th--16th weeks of age. As evidenced by the higher percentages of esterified cholesterol at all the ages studied, it is suggested that the Nigerian male fowl is an early-maturing specie.", "contents": "Age-influence variations in the levels of cholesterol and ATPase activity in the testes of prepuberal chicks. Changes in the levels of total, free and esterified cholesterol and ATPase activity were measured in male prepuberal Nigerian fowl. Results showed that in all cases, the testicular levels of these parameters increased to peak levels and decreased thereafter. Total and free cholesterol levels were maximal at 12 weeks while the esterification of cholesterol was maintained from 14 weeks through to the 16th week. The results of ATPase activity corroborated these findings. The data suggest that peak androgen formation occurred in these chicks between 14th--16th weeks of age. As evidenced by the higher percentages of esterified cholesterol at all the ages studied, it is suggested that the Nigerian male fowl is an early-maturing specie."}
{"id": "PMID:203919", "title": "The infectivity of fluid from regressing Rous sarcomas.", "content": "Fluid was withdrawn from the site of regressing Rous sarcomas in chickens and inoculated into the wing-webs of untreated chickens from three strains of chickens with divergent degrees of resistance to Rous sarcomas. The transfer of fluid initiated progressive tumors in all three strains of chickens. The infectivity of the fluid was apparently due to tumor cells and not to virus.", "contents": "The infectivity of fluid from regressing Rous sarcomas. Fluid was withdrawn from the site of regressing Rous sarcomas in chickens and inoculated into the wing-webs of untreated chickens from three strains of chickens with divergent degrees of resistance to Rous sarcomas. The transfer of fluid initiated progressive tumors in all three strains of chickens. The infectivity of the fluid was apparently due to tumor cells and not to virus."}
{"id": "PMID:203920", "title": "Intestinal calcium binding protein levels in the one month old turkey poult.", "content": "Intestinal calcium binding protein CaBP) was studied in one month old poults which had been fed a vitamin D3-deficient diet unsupplemented or with 399, 600, 900 or 1200 I.U. vitamin D3 added per kg. diet. CaBP levels increased with vitamin D3 supplementation up to 600 I.U. but showed no further increase with higher dietary vitamin D3. Poults supplemented with 600 to 1200 I.U. vitamin D3/kg. diet had an average of 1.03 mg. CaBP/g. of duodenal mucosa cells collected. The calcium binding activity of these samples was approximately 0.9% per mg. protein and was highly correlated with CaBP concentration (r=0.94).", "contents": "Intestinal calcium binding protein levels in the one month old turkey poult. Intestinal calcium binding protein CaBP) was studied in one month old poults which had been fed a vitamin D3-deficient diet unsupplemented or with 399, 600, 900 or 1200 I.U. vitamin D3 added per kg. diet. CaBP levels increased with vitamin D3 supplementation up to 600 I.U. but showed no further increase with higher dietary vitamin D3. Poults supplemented with 600 to 1200 I.U. vitamin D3/kg. diet had an average of 1.03 mg. CaBP/g. of duodenal mucosa cells collected. The calcium binding activity of these samples was approximately 0.9% per mg. protein and was highly correlated with CaBP concentration (r=0.94)."}
{"id": "PMID:203922", "title": "Immunization of chickens against adenovirus infection.", "content": "Chickens were vaccinated with monovalent and polyvalent adenovirus vaccines using three different serotypes, types 1, 2, and 3. No cross-protection was elicited by the heterologous serotypes but satisfactory protection from lesions and the shedding of challenge virus was induced by the homologous serotypes in the monovalent and polyvalent vaccines. The virus neutralizing (VN) titers were occasionally lower where the polyvalent vaccines were used when compared to those from chickens given the monovalent vaccines. This suggested possible interference though protection did exist against the appearance of lesions. Where chickens were vaccinated at an early age and in the presence of congenital homologous VN antibodies, protection against the effects of infection was satisfactory whereas the VN antibody titers were low or insignificant by the assay methods employed. The vaccine virus was not shed beyond 28 days after vaccination. No physical effects of vaccination were noted in any of the chickens during the post-vaccination period.", "contents": "Immunization of chickens against adenovirus infection. Chickens were vaccinated with monovalent and polyvalent adenovirus vaccines using three different serotypes, types 1, 2, and 3. No cross-protection was elicited by the heterologous serotypes but satisfactory protection from lesions and the shedding of challenge virus was induced by the homologous serotypes in the monovalent and polyvalent vaccines. The virus neutralizing (VN) titers were occasionally lower where the polyvalent vaccines were used when compared to those from chickens given the monovalent vaccines. This suggested possible interference though protection did exist against the appearance of lesions. Where chickens were vaccinated at an early age and in the presence of congenital homologous VN antibodies, protection against the effects of infection was satisfactory whereas the VN antibody titers were low or insignificant by the assay methods employed. The vaccine virus was not shed beyond 28 days after vaccination. No physical effects of vaccination were noted in any of the chickens during the post-vaccination period."}
{"id": "PMID:203923", "title": "Effect of infectious bursal disease virus on the immunological responsiveness of the chicken.", "content": "The immunological response of chickens infected at 28 days of age with infectious bursal disease virus (IBDV) was examined. Cellular immunity was studied by the graft-versus-host reaction and delayed type hypersensitivity skin reactions to tuberculin. Antibody responses to sheep red blood cells (S-RBC's) were tested by a direct hemagglutination test. Circulating levels of immunoglobulins (Ig's) IgM, IgG and IgA were monitored by the radial immunodiffusion test. The results of the graft-versus-host reaction and delayed type hypersensitivity reactions were similar for both the infected and control chicks. IBDV significantly reduced the primary antibody response to S-RBC's, but had no marked effect on the secondary antibody response. Chicks infected with IBDV had normal levels of serum IgM and IgG, but significantly lower levels of IgA when compared to uninfected control birds.", "contents": "Effect of infectious bursal disease virus on the immunological responsiveness of the chicken. The immunological response of chickens infected at 28 days of age with infectious bursal disease virus (IBDV) was examined. Cellular immunity was studied by the graft-versus-host reaction and delayed type hypersensitivity skin reactions to tuberculin. Antibody responses to sheep red blood cells (S-RBC's) were tested by a direct hemagglutination test. Circulating levels of immunoglobulins (Ig's) IgM, IgG and IgA were monitored by the radial immunodiffusion test. The results of the graft-versus-host reaction and delayed type hypersensitivity reactions were similar for both the infected and control chicks. IBDV significantly reduced the primary antibody response to S-RBC's, but had no marked effect on the secondary antibody response. Chicks infected with IBDV had normal levels of serum IgM and IgG, but significantly lower levels of IgA when compared to uninfected control birds."}
{"id": "PMID:203925", "title": "The enzymic preparation of diphosphoinositides.", "content": "A procedure for the preparation of diphosphoinositides is described. Triphosphoinositides isolated from bovine brain are hydrolysed by the triphosphoinositide phosphatase (EC 3.1.3.36) from Crithidia fasciculata in the presence of MgC12 and cetyltrimethyl-ammonium bromide. The diphosphoinositides produced are not degraded further and can be recovered from the reaction mixture in greater than 80% yield. The product is chromatographically pure and has the same structure (1-phosphatidylinositol 4-phosphate) as naturally occurring diphosphoinositides.", "contents": "The enzymic preparation of diphosphoinositides. A procedure for the preparation of diphosphoinositides is described. Triphosphoinositides isolated from bovine brain are hydrolysed by the triphosphoinositide phosphatase (EC 3.1.3.36) from Crithidia fasciculata in the presence of MgC12 and cetyltrimethyl-ammonium bromide. The diphosphoinositides produced are not degraded further and can be recovered from the reaction mixture in greater than 80% yield. The product is chromatographically pure and has the same structure (1-phosphatidylinositol 4-phosphate) as naturally occurring diphosphoinositides."}
{"id": "PMID:203926", "title": "Organization and expression of early genes of simian virus 40.", "content": "The early region of simian virus 40 codes for at least two immunologically related polypeptides: large-T and small-t, with apparent molecular weights of 90,000-100,000 and 15,000-20,000, respectively. Because small-t shares methionine-containing tryptic peptides with large-T, the two polypeptides are probably coded, in part, by a common nucleotide sequence. To locate the coding sequences for large-T and small-t in the DNA, the production of these proteins was examined after infection of CV-1 cells with wild-type and deletion mutants of simian virus 40. We found that a deletion at the distal portion of the early region alters the structure of large-T but not of small-t; but deletions within the region between map coordinates 0.59 and 0.55 result in an alteration or absence of small-t and a normal large-T. These findings have been rationalized by a model that proposes the existence of two early mRNAs, one coding for large-T and the other for small-t. Both mRNAs span virtually the entire early region; but the mRNA coding for large-T lacks the nucleotide sequence between map coordinates 0.59 and 0.54. We suggest that small-t is translated from the larger of the two mRNAs, beginning at or near its 5' end and terminating at a termination codon at about map coordinate 0.54. Larger-T, on the other hand, is translated from the shorter mRNA, beginning at the same initiator codon, and, because of the deletion of the terminator codon at 0.54, translation proceeds to the terminator codon at or near map position 0.18.", "contents": "Organization and expression of early genes of simian virus 40. The early region of simian virus 40 codes for at least two immunologically related polypeptides: large-T and small-t, with apparent molecular weights of 90,000-100,000 and 15,000-20,000, respectively. Because small-t shares methionine-containing tryptic peptides with large-T, the two polypeptides are probably coded, in part, by a common nucleotide sequence. To locate the coding sequences for large-T and small-t in the DNA, the production of these proteins was examined after infection of CV-1 cells with wild-type and deletion mutants of simian virus 40. We found that a deletion at the distal portion of the early region alters the structure of large-T but not of small-t; but deletions within the region between map coordinates 0.59 and 0.55 result in an alteration or absence of small-t and a normal large-T. These findings have been rationalized by a model that proposes the existence of two early mRNAs, one coding for large-T and the other for small-t. Both mRNAs span virtually the entire early region; but the mRNA coding for large-T lacks the nucleotide sequence between map coordinates 0.59 and 0.54. We suggest that small-t is translated from the larger of the two mRNAs, beginning at or near its 5' end and terminating at a termination codon at about map coordinate 0.54. Larger-T, on the other hand, is translated from the shorter mRNA, beginning at the same initiator codon, and, because of the deletion of the terminator codon at 0.54, translation proceeds to the terminator codon at or near map position 0.18."}
{"id": "PMID:203927", "title": "Spin labeling of a cysteine residue of the Escherichia coli outer membrane lipoprotein in its membrane environment.", "content": "A method was developed to attach a spin label to a specific site on the structural lipoprotein of the Escherichia coli outer membrane in situ. This method takes advantage of the fact that the outer membrane of wild-type E. coli contains few residues reactive towards sulfhydryl reagents. A mutant E. coli strain has been isolated [Suzuki, H., Nishimura, Y., Iketani, H., Campisi, J., Hirashima, A., Inouye, M. & Hirota, Y. (1976) J. Bacteriol. 127, 1494-1501] in which the second position from the carboxy terminus of the lipoprotein is changed from arginine into a cysteine residue. The membrane fraction of this mutant was treated with N-(1-oxyl-2,2,5,5-tetramethylpyrrolidinyl)maleimide in the presence of EDTA and 2-mercaptoethanol. Spin label was found to be preferentially incorporated into the lipoprotein. The spectrum of the spin-labeled membrane shows two components, both arising from spin label at the same site near the carboxy terminus. The strongly immobilized component has a maximum hyperfine splitting value of 53 G, and the weakly immobilized component, 37 G. A fraction of the lipoprotein is covalently bound to the peptidoglycan layer through its carboxy-terminal lysine; the spectrum of the isolated bound form of the lipoprotein was identical to that of the free form. When the matrix protein, the other major outer membrane protein, was removed by mutation, the spectrum of the lipoprotein was altered, suggesting that these two proteins are closely associated.", "contents": "Spin labeling of a cysteine residue of the Escherichia coli outer membrane lipoprotein in its membrane environment. A method was developed to attach a spin label to a specific site on the structural lipoprotein of the Escherichia coli outer membrane in situ. This method takes advantage of the fact that the outer membrane of wild-type E. coli contains few residues reactive towards sulfhydryl reagents. A mutant E. coli strain has been isolated [Suzuki, H., Nishimura, Y., Iketani, H., Campisi, J., Hirashima, A., Inouye, M. & Hirota, Y. (1976) J. Bacteriol. 127, 1494-1501] in which the second position from the carboxy terminus of the lipoprotein is changed from arginine into a cysteine residue. The membrane fraction of this mutant was treated with N-(1-oxyl-2,2,5,5-tetramethylpyrrolidinyl)maleimide in the presence of EDTA and 2-mercaptoethanol. Spin label was found to be preferentially incorporated into the lipoprotein. The spectrum of the spin-labeled membrane shows two components, both arising from spin label at the same site near the carboxy terminus. The strongly immobilized component has a maximum hyperfine splitting value of 53 G, and the weakly immobilized component, 37 G. A fraction of the lipoprotein is covalently bound to the peptidoglycan layer through its carboxy-terminal lysine; the spectrum of the isolated bound form of the lipoprotein was identical to that of the free form. When the matrix protein, the other major outer membrane protein, was removed by mutation, the spectrum of the lipoprotein was altered, suggesting that these two proteins are closely associated."}
{"id": "PMID:203928", "title": "Similarity of nucleotide sequences around the origin of DNA replication in mouse polyoma virus and simian virus 40.", "content": "The nucleotide sequence around the origin of replication in DNA of mouse polyoma virus was determined by 32P labeling of the 3' terminus of the Hap II-5/Alu I-1 DNA fragment, with the use of DNA polymerase. The result coincided with our previous report on the 32P labeling, with the use of polynucleotide kinase, of the 5' terminus of the Hap II-5/Hha I-1 DNA fragment, which corresponds to the large part of the present fragment, Hap II-5/Alu I-1. A symmetrical (A+T)-rich region containing a five-A stretch (or a five-T stretch) was flanked by two small regions with a 2-fold rotational axis of symmetry. On comparison of the sequence near the replication origin of polyoma DNA with that in the corresponding region of simian virus 40 DNA, which was included in the EcoRI-G fragment sequenced by Weissman's group (Subramanian K.N., Dahr, R. & Weissman, S. M. (1977) J. Biol. Chem. 252, 355--367), a considerable similarity was detected. Several possible common sequences for important biological activities such as the starting of DNA replication and RNA synthesis were suggested.", "contents": "Similarity of nucleotide sequences around the origin of DNA replication in mouse polyoma virus and simian virus 40. The nucleotide sequence around the origin of replication in DNA of mouse polyoma virus was determined by 32P labeling of the 3' terminus of the Hap II-5/Alu I-1 DNA fragment, with the use of DNA polymerase. The result coincided with our previous report on the 32P labeling, with the use of polynucleotide kinase, of the 5' terminus of the Hap II-5/Hha I-1 DNA fragment, which corresponds to the large part of the present fragment, Hap II-5/Alu I-1. A symmetrical (A+T)-rich region containing a five-A stretch (or a five-T stretch) was flanked by two small regions with a 2-fold rotational axis of symmetry. On comparison of the sequence near the replication origin of polyoma DNA with that in the corresponding region of simian virus 40 DNA, which was included in the EcoRI-G fragment sequenced by Weissman's group (Subramanian K.N., Dahr, R. & Weissman, S. M. (1977) J. Biol. Chem. 252, 355--367), a considerable similarity was detected. Several possible common sequences for important biological activities such as the starting of DNA replication and RNA synthesis were suggested."}
{"id": "PMID:203929", "title": "Isotopic (18O) shift in 31P nuclear magnetic resonance applied to a study of enzyme-catalyzed phosphate--phosphate exchange and phosphate (oxygen)--water exchange reactions.", "content": "An isotopic shift of the (31)P nuclear magnetic resonance due to (18)O bonded to phosphorus of 0.0206 ppm has been observed in inorganic orthophosphate and adenine nucleotides. Thus, the separation between the resonances of (31)P(18)O(4) and (31)P(16)O(4) at 145.7 MHz is 12 Hz and, in a randomized sample containing approximately 50% (18)O, all five (16)O-(18)O species are resolved and separated from each other by 3 Hz. Not only does this yield the (18)O/(16)O ratio of the phosphate but, more important, the (18)O-labeled phosphate in effect can serve as a double label in following phosphate reactions, for oxygen in all cases and for phosphorus, provided the oxygen does not exchange with solvent water. Thus, it becomes possible to follow labeled phosphorus or labeled oxygen continuously as reactions proceed. Rate studies involving (i) phosphorus and (ii) oxygen are illustrated by continuous monitoring of the exchange reactions between (i) the beta phosphate of ADP and inorganic phosphate catalyzed by polynucleotide phosphorylase and (ii) inorganic orthophosphate and water catalyzed by yeast inorganic pyrophosphatase. In the ADP-P(i) exchange, the P(i) ((18)O(4)) yielded an alpha P((16)O(3) (18)O) and a beta P((18)O(4)), proving that bond cleavage occurs between the alpha P and the alpha-beta bridge oxygen. Among the many additional potential uses of this labeling technique and its spectroscopic observation are: (i) different labeling of each phosphate group of ATP, (ii) to follow rate of transfer of (18)O from a nonphosphate compound such as a carboxylic acid to a phosphate compound, and (iii) to follow the rate of scrambling (for example, of the beta-gamma bridge oxygen of ATP to nonbridge beta P positions) and simultaneously the rate of exchange of the gamma P nonbridge oxygens with solvent water in various ATPase reactions.", "contents": "Isotopic (18O) shift in 31P nuclear magnetic resonance applied to a study of enzyme-catalyzed phosphate--phosphate exchange and phosphate (oxygen)--water exchange reactions. An isotopic shift of the (31)P nuclear magnetic resonance due to (18)O bonded to phosphorus of 0.0206 ppm has been observed in inorganic orthophosphate and adenine nucleotides. Thus, the separation between the resonances of (31)P(18)O(4) and (31)P(16)O(4) at 145.7 MHz is 12 Hz and, in a randomized sample containing approximately 50% (18)O, all five (16)O-(18)O species are resolved and separated from each other by 3 Hz. Not only does this yield the (18)O/(16)O ratio of the phosphate but, more important, the (18)O-labeled phosphate in effect can serve as a double label in following phosphate reactions, for oxygen in all cases and for phosphorus, provided the oxygen does not exchange with solvent water. Thus, it becomes possible to follow labeled phosphorus or labeled oxygen continuously as reactions proceed. Rate studies involving (i) phosphorus and (ii) oxygen are illustrated by continuous monitoring of the exchange reactions between (i) the beta phosphate of ADP and inorganic phosphate catalyzed by polynucleotide phosphorylase and (ii) inorganic orthophosphate and water catalyzed by yeast inorganic pyrophosphatase. In the ADP-P(i) exchange, the P(i) ((18)O(4)) yielded an alpha P((16)O(3) (18)O) and a beta P((18)O(4)), proving that bond cleavage occurs between the alpha P and the alpha-beta bridge oxygen. Among the many additional potential uses of this labeling technique and its spectroscopic observation are: (i) different labeling of each phosphate group of ATP, (ii) to follow rate of transfer of (18)O from a nonphosphate compound such as a carboxylic acid to a phosphate compound, and (iii) to follow the rate of scrambling (for example, of the beta-gamma bridge oxygen of ATP to nonbridge beta P positions) and simultaneously the rate of exchange of the gamma P nonbridge oxygens with solvent water in various ATPase reactions."}
{"id": "PMID:203930", "title": "Specific regulation by steroid hormones of the amount of type I cyclic AMP-dependent protein kinase holoenzyme.", "content": "The total amounts of type I and type II cytoplasmic cyclic AMP-dependent protein kinase activities were measured in various tissues of intact rats and rats subjected to castration, hypophysectomy, or adrenalectomy. After castration, the total amount of type I activity decreased rapidly in classifically steroid-responsive tissues such as the ventral prostate and levator ani muscle and less rapidly in the liver. After hypophysectomy and adrenalectomy, type I activity in the liver decreased to the same extent as after castration. Type I activity could be maintained in the ventral prostate and levator ani muscle at control levels by the daily injection of dihydrotestosterone. Furthermore, after post-castration regression of the prostate for 3 days, three daily subcutaneous injections of dihydrotestosterone resulted in a complete restoration of type I activity toe the intact level. The amount of type II activity was not altered by any of the experimental ablations. This study provides evidence linking steroid action to the ability of steroid-responsive tissues to maintain a substantial activity of type I cyclic AMP-dependent protein kinase.", "contents": "Specific regulation by steroid hormones of the amount of type I cyclic AMP-dependent protein kinase holoenzyme. The total amounts of type I and type II cytoplasmic cyclic AMP-dependent protein kinase activities were measured in various tissues of intact rats and rats subjected to castration, hypophysectomy, or adrenalectomy. After castration, the total amount of type I activity decreased rapidly in classifically steroid-responsive tissues such as the ventral prostate and levator ani muscle and less rapidly in the liver. After hypophysectomy and adrenalectomy, type I activity in the liver decreased to the same extent as after castration. Type I activity could be maintained in the ventral prostate and levator ani muscle at control levels by the daily injection of dihydrotestosterone. Furthermore, after post-castration regression of the prostate for 3 days, three daily subcutaneous injections of dihydrotestosterone resulted in a complete restoration of type I activity toe the intact level. The amount of type II activity was not altered by any of the experimental ablations. This study provides evidence linking steroid action to the ability of steroid-responsive tissues to maintain a substantial activity of type I cyclic AMP-dependent protein kinase."}
{"id": "PMID:203931", "title": "Uracil incorporation: a source of pulse-labeled DNA fragments in the replication of the Escherichia coli chromosome.", "content": "Uracil is incorporated into newly synthesized DNA by mutants of Escherichia coli with reduced levels of dUTPase (dUTP nucleotidohydrolase; EC 3.6.1.23). Excision-repair of the incorporated uracil results in the generation of labeled DNA fragments that appear after brief pulses with [(3)H]thymidine [Tye, B-K., Nyman, P.-D., Lehman, I. R., Hochhauser, S. & Weiss, B. (1977) Proc. Natl. Acad. Sci. USA 74, 154-157]. Uracil is also incorporated into the newly synthesized DNA of strains of E. coli that contain normal levels of dUTPase. DNA fragments generated by the postreplication excision-repair of uracil may therefore contribute to the pool of nascent DNA (Okazaki) fragments that normally appear in wild-type strains. Discontinuous DNA replication has been examined in the absence of uracil excision by comparing Okazaki fragments in strains that are defective in DNA polymerase I (polA(-)) and polA(-) strains that are also defective in uracil N-glycosidase, an enzyme required for the excision-repair of uracil in DNA (polA(-)ung(-)). Little or no difference was detected in the level of Okazaki fragments in the polA(-) strain as compared with the polA(-)ung(-) strain. Thus, the uracil-induced cleavage of DNA cannot be the sole mechanism for the generation of Okazaki fragments. Mutants that are defective both in dUTPase and in uracil N-glycosidase incorporate uracil into their DNA with a high frequency (up to 1 per 100 nucleotides). These uracil residues, once incorporated, persist in the DNA without an adverse affect on the growth of the cells.", "contents": "Uracil incorporation: a source of pulse-labeled DNA fragments in the replication of the Escherichia coli chromosome. Uracil is incorporated into newly synthesized DNA by mutants of Escherichia coli with reduced levels of dUTPase (dUTP nucleotidohydrolase; EC 3.6.1.23). Excision-repair of the incorporated uracil results in the generation of labeled DNA fragments that appear after brief pulses with [(3)H]thymidine [Tye, B-K., Nyman, P.-D., Lehman, I. R., Hochhauser, S. & Weiss, B. (1977) Proc. Natl. Acad. Sci. USA 74, 154-157]. Uracil is also incorporated into the newly synthesized DNA of strains of E. coli that contain normal levels of dUTPase. DNA fragments generated by the postreplication excision-repair of uracil may therefore contribute to the pool of nascent DNA (Okazaki) fragments that normally appear in wild-type strains. Discontinuous DNA replication has been examined in the absence of uracil excision by comparing Okazaki fragments in strains that are defective in DNA polymerase I (polA(-)) and polA(-) strains that are also defective in uracil N-glycosidase, an enzyme required for the excision-repair of uracil in DNA (polA(-)ung(-)). Little or no difference was detected in the level of Okazaki fragments in the polA(-) strain as compared with the polA(-)ung(-) strain. Thus, the uracil-induced cleavage of DNA cannot be the sole mechanism for the generation of Okazaki fragments. Mutants that are defective both in dUTPase and in uracil N-glycosidase incorporate uracil into their DNA with a high frequency (up to 1 per 100 nucleotides). These uracil residues, once incorporated, persist in the DNA without an adverse affect on the growth of the cells."}
{"id": "PMID:203932", "title": "DNA intermediates at the Escherichia coli replication fork: effect of dUTP.", "content": "We have directly tested the hypothesis that elevated levels of dUTP cause the formation of small DNA fragments at the replication fork of Escherichia coli. Addition of increasing levels of dUTP to lysates on cellophane discs results in an increasing number of strand scissions in the newly replicated DNA. Lysates of strains defective in dUTPase produce many more scissions at the same level of dUTP. The size distribution of Okazaki pieces obtained in vivo can be reconstituted in vitro on cellophane discs if appropriate levels of dUTP are present. Although uracil excision leads to the apparent production of Okazaki pieces from both daughter strands, DNA synthesis is actually asymmetric under these conditions. De novo chain initiation events occur on only one strand. It is suggested that asymmetry of synthesis in vivo may be masked by uracil excision and other postreplication processing mechanisms.", "contents": "DNA intermediates at the Escherichia coli replication fork: effect of dUTP. We have directly tested the hypothesis that elevated levels of dUTP cause the formation of small DNA fragments at the replication fork of Escherichia coli. Addition of increasing levels of dUTP to lysates on cellophane discs results in an increasing number of strand scissions in the newly replicated DNA. Lysates of strains defective in dUTPase produce many more scissions at the same level of dUTP. The size distribution of Okazaki pieces obtained in vivo can be reconstituted in vitro on cellophane discs if appropriate levels of dUTP are present. Although uracil excision leads to the apparent production of Okazaki pieces from both daughter strands, DNA synthesis is actually asymmetric under these conditions. De novo chain initiation events occur on only one strand. It is suggested that asymmetry of synthesis in vivo may be masked by uracil excision and other postreplication processing mechanisms."}
{"id": "PMID:203933", "title": "In vivo phosphorylation of a synthetic peptide substrate of cyclic AMP-dependent protein kinase.", "content": "A model synthetic peptide substrate of the cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase; EC 2.7.1.37), Leu-Arg-Arg-Ala-Ser-Leu-Gly, closely resembling the local phosphorylation site sequence in porcine hepatic pyruvate kinase, was shown to be phosphorylated in vivo after microinjection into Xenopus oocytes. This result demonstrates that the microinjection technique, utilizing a synthetic peptide substrate, or possibly a synthetic substrate analog inhibitor [Kemp, B. E., Benjamini, E. & Krebs, E. G. (1976) Proc. Natl. Acad. Sci. USA 73, 1038--1042], can be used to study protein phosphorylation-dephosphorylation reactions in living oocytes. This follows, since it is clear that the injected peptide was accessible to the cellular compartment containing the protein kinase.", "contents": "In vivo phosphorylation of a synthetic peptide substrate of cyclic AMP-dependent protein kinase. A model synthetic peptide substrate of the cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase; EC 2.7.1.37), Leu-Arg-Arg-Ala-Ser-Leu-Gly, closely resembling the local phosphorylation site sequence in porcine hepatic pyruvate kinase, was shown to be phosphorylated in vivo after microinjection into Xenopus oocytes. This result demonstrates that the microinjection technique, utilizing a synthetic peptide substrate, or possibly a synthetic substrate analog inhibitor [Kemp, B. E., Benjamini, E. & Krebs, E. G. (1976) Proc. Natl. Acad. Sci. USA 73, 1038--1042], can be used to study protein phosphorylation-dephosphorylation reactions in living oocytes. This follows, since it is clear that the injected peptide was accessible to the cellular compartment containing the protein kinase."}
{"id": "PMID:203934", "title": "Evidence for the presence of two nonidentical subunits in NAD-dependent isocitrate dehydrogenase of pig heart.", "content": "The NAD-dependent isocitrate dehydrogenase [threo-D(S)-isocitrate:NAD(+) oxidoreductase (decarboxylating); EC 1.1.1.41] from pig heart is a multisubunit enzyme with a molecular weight of approximately 340,000. Electrophoresis of the enzyme in 10% polyacrylamide gels containing sodium dodecyl sulfate reveals two discrete bands with molecular weights of 41,000 and 39,000. The two bands exhibit approximately equal intensity when stained with Coomassie Blue, Amido Black, and Bromophenol Blue, suggesting that these polypeptide chains are present in equimolar quantities in the native enzyme. The same two-band pattern is observed when the sulfhydryl groups of the enzyme are blocked by alkylation with iodoacetate prior to electrophoresis, indicating that sulfhydryl oxidation is not responsible for the observed heterogeneity. Each of the subunits appears as a single band when eluted from the gel and again subjected to electrophoresis under the same conditions. Isocitrate dehydrogenase contains a total of 41 lysine and arginine residues per average subunit of 40,000 daltons. The observation of approximately 80 peptides upon paper chromatography and high voltage electrophoresis of tryptic digests of the enzyme is consistent with the existence of two distinct polypeptide chains. Dansylation yields two NH(2)-terminal amino acid derivatives: dansyl-phenylalanine and dansyl-alanine. It is concluded that the NAD-specific isocitrate dehydrogenase is composed of equal numbers of two nonidentical subunits.", "contents": "Evidence for the presence of two nonidentical subunits in NAD-dependent isocitrate dehydrogenase of pig heart. The NAD-dependent isocitrate dehydrogenase [threo-D(S)-isocitrate:NAD(+) oxidoreductase (decarboxylating); EC 1.1.1.41] from pig heart is a multisubunit enzyme with a molecular weight of approximately 340,000. Electrophoresis of the enzyme in 10% polyacrylamide gels containing sodium dodecyl sulfate reveals two discrete bands with molecular weights of 41,000 and 39,000. The two bands exhibit approximately equal intensity when stained with Coomassie Blue, Amido Black, and Bromophenol Blue, suggesting that these polypeptide chains are present in equimolar quantities in the native enzyme. The same two-band pattern is observed when the sulfhydryl groups of the enzyme are blocked by alkylation with iodoacetate prior to electrophoresis, indicating that sulfhydryl oxidation is not responsible for the observed heterogeneity. Each of the subunits appears as a single band when eluted from the gel and again subjected to electrophoresis under the same conditions. Isocitrate dehydrogenase contains a total of 41 lysine and arginine residues per average subunit of 40,000 daltons. The observation of approximately 80 peptides upon paper chromatography and high voltage electrophoresis of tryptic digests of the enzyme is consistent with the existence of two distinct polypeptide chains. Dansylation yields two NH(2)-terminal amino acid derivatives: dansyl-phenylalanine and dansyl-alanine. It is concluded that the NAD-specific isocitrate dehydrogenase is composed of equal numbers of two nonidentical subunits."}
{"id": "PMID:203935", "title": "Relationship between dibutyryl cyclic AMP and microtubule organization in contracting heart muscle cells.", "content": "Rhythmic and synchronous contractions of interconnecting myocyte cultures prepared from fetal rat hearts are arrested upon the addition of 0.2--2.0 mM N6, O2'-dibuturyladenosine 3':5'-cyclic monophosphate (Bt2cAMP). The contractions arrested by Bt2cAMP are restored either by diluting the Bt2cAMP from the media or by adding colchicine. While colchicine restores Bt2cAMP-arrested myocyte contractions at concentrations as low as 1.0 micron, the inactive isomer lumicolchicine shows no effect. Morphologically, Bt2cAMP treatment of myocyte cultures results in the appearance of numerous elongated cellular processes not present in control cultures. Ultrastructural examination indicates that in Bt2cAMP-treated cells the intracellular distribution of microtubules is altered such that these organelles appear to accumulate in parallel arrays. In cells not treated with Bt2cAMP, the microtubules appear randomly oriented, while in cells treated with only colchicine, intact microtubules are not observed. The relationship between microtubules an heart cell contraction is discussed.", "contents": "Relationship between dibutyryl cyclic AMP and microtubule organization in contracting heart muscle cells. Rhythmic and synchronous contractions of interconnecting myocyte cultures prepared from fetal rat hearts are arrested upon the addition of 0.2--2.0 mM N6, O2'-dibuturyladenosine 3':5'-cyclic monophosphate (Bt2cAMP). The contractions arrested by Bt2cAMP are restored either by diluting the Bt2cAMP from the media or by adding colchicine. While colchicine restores Bt2cAMP-arrested myocyte contractions at concentrations as low as 1.0 micron, the inactive isomer lumicolchicine shows no effect. Morphologically, Bt2cAMP treatment of myocyte cultures results in the appearance of numerous elongated cellular processes not present in control cultures. Ultrastructural examination indicates that in Bt2cAMP-treated cells the intracellular distribution of microtubules is altered such that these organelles appear to accumulate in parallel arrays. In cells not treated with Bt2cAMP, the microtubules appear randomly oriented, while in cells treated with only colchicine, intact microtubules are not observed. The relationship between microtubules an heart cell contraction is discussed."}
{"id": "PMID:203936", "title": "Carcinogens enhance survival of UV-irradiated simian virus 40 in treated monkey kidney cells: induction of a recovery pathway?", "content": "Treatment of monkey kidney cells with low doses of carcinogen enhances the survival of UV-irradiated simian virus 40 (SV40). This is true for compounds with UV-like effects (metabolites of aflatoxin B1, N-acetoxyacetylaminofluorene) and compounds with x-ray-like effects (methyl methanesulfonate, ethyl methanesulfonate). This phenomenon resembles the UV-reactivation of viruses in eukaryotic cells. The carcinogen-induced enhancement of the survival of UV-irradiated SV40 is correlated with the inhibition of host-cell DNA synthesis, suggesting that the inhibition is an inducing agent. An enhancement of UV-irradiated SV40 survival is also obtained in cells treated with hydroxyurea or cycloheximide for long enough that there is still inhibition of host DNA synthesis during the early stage of SV40 infection. We hypothesize that treatment of host cells with carcinogens induces a new recovery pathway that facilitates the replication of damaged DNA, bypassing the lesions and resulting in the enhanced survival of UV-irradiated SV40. This inducible process might represent the expression of \"SOS repair\" functions in eukaryotic cells analogous to the previously demonstrated induction of SOS repair in bacteria after UV or carcinogen treatment.", "contents": "Carcinogens enhance survival of UV-irradiated simian virus 40 in treated monkey kidney cells: induction of a recovery pathway? Treatment of monkey kidney cells with low doses of carcinogen enhances the survival of UV-irradiated simian virus 40 (SV40). This is true for compounds with UV-like effects (metabolites of aflatoxin B1, N-acetoxyacetylaminofluorene) and compounds with x-ray-like effects (methyl methanesulfonate, ethyl methanesulfonate). This phenomenon resembles the UV-reactivation of viruses in eukaryotic cells. The carcinogen-induced enhancement of the survival of UV-irradiated SV40 is correlated with the inhibition of host-cell DNA synthesis, suggesting that the inhibition is an inducing agent. An enhancement of UV-irradiated SV40 survival is also obtained in cells treated with hydroxyurea or cycloheximide for long enough that there is still inhibition of host DNA synthesis during the early stage of SV40 infection. We hypothesize that treatment of host cells with carcinogens induces a new recovery pathway that facilitates the replication of damaged DNA, bypassing the lesions and resulting in the enhanced survival of UV-irradiated SV40. This inducible process might represent the expression of \"SOS repair\" functions in eukaryotic cells analogous to the previously demonstrated induction of SOS repair in bacteria after UV or carcinogen treatment."}
{"id": "PMID:203937", "title": "Role of contact inhibition in the regulation of receptor-mediated uptake of low density lipoprotein in cultured vascular endothelial cells.", "content": "Bovine vascular endothelial cells during logarithmic growth bind, internalize, and degrade low density lipoprotein (LDL) via a receptor-mediated pathway. However, contact-inhibited (confluent) monolayers bind but do not internalize LDL. This is in contrast to aortic smooth muscle cells or endothelial cells that have lost the property of contact inhibition. These cells internalize and degrade LDL at both high and low cell densities. The LDL receptors of smooth muscle and sparse endothelial cells down-regulate in response to LDL. In contrast, normal endothelial cells at confluency show little response. When contact inhibition in endothelial monolayers was locally released by wounding, and LDL was present, only cells released from contact inhibition accumulated LDL cholesterol. In smooth muscle cells under the same conditions, the entire culture interiorized lipid. It thus appears that in endothelial cells, unlike smooth muscle cells, contact inhibition is the major factor regulating cellular uptake of LDL cholesteryl ester. Reversal of contact inhibition by wounding provides a mechanism by which the endothelium could be the primary initiator of the atherosclerotic plaque.", "contents": "Role of contact inhibition in the regulation of receptor-mediated uptake of low density lipoprotein in cultured vascular endothelial cells. Bovine vascular endothelial cells during logarithmic growth bind, internalize, and degrade low density lipoprotein (LDL) via a receptor-mediated pathway. However, contact-inhibited (confluent) monolayers bind but do not internalize LDL. This is in contrast to aortic smooth muscle cells or endothelial cells that have lost the property of contact inhibition. These cells internalize and degrade LDL at both high and low cell densities. The LDL receptors of smooth muscle and sparse endothelial cells down-regulate in response to LDL. In contrast, normal endothelial cells at confluency show little response. When contact inhibition in endothelial monolayers was locally released by wounding, and LDL was present, only cells released from contact inhibition accumulated LDL cholesterol. In smooth muscle cells under the same conditions, the entire culture interiorized lipid. It thus appears that in endothelial cells, unlike smooth muscle cells, contact inhibition is the major factor regulating cellular uptake of LDL cholesteryl ester. Reversal of contact inhibition by wounding provides a mechanism by which the endothelium could be the primary initiator of the atherosclerotic plaque."}
{"id": "PMID:203938", "title": "Multiple forms of sarc gene proteins from Rous sarcoma virus RNA.", "content": "In a previous study we were able to identify two proteins of 25,000 and 18,000 daltons that were made from RNA of transforming virions of Rous sarcoma virus (RSV) and that were missing from the translation products of a transformation-defective deletion mutant of RSV. In the present study we have separated RSV virion RNA on sucrose gradients and have determined that the two putative sarc gene products are synthesized as doublets from an mRNA of approximately 18 S. There also appear to be several other sizes of virion mRNA that direct the synthesis of other viral proteins. These data are discussed in terms of the structure of the RSV genome. In addition to the 25,000- and 18,000-dalton doublets, there also is a 60,000-dalton protein whose synthesis is directed by 18S viral RNA from transforming virion of RSV. Peptide mapping has shown that the 60,000- and 25,000-dalton doublet are structurally related. In addition, the use of two-dimensional gel electrophoresis has allowed us to resolve both bands of the 25,000-dalton doublet into several differently charged species.", "contents": "Multiple forms of sarc gene proteins from Rous sarcoma virus RNA. In a previous study we were able to identify two proteins of 25,000 and 18,000 daltons that were made from RNA of transforming virions of Rous sarcoma virus (RSV) and that were missing from the translation products of a transformation-defective deletion mutant of RSV. In the present study we have separated RSV virion RNA on sucrose gradients and have determined that the two putative sarc gene products are synthesized as doublets from an mRNA of approximately 18 S. There also appear to be several other sizes of virion mRNA that direct the synthesis of other viral proteins. These data are discussed in terms of the structure of the RSV genome. In addition to the 25,000- and 18,000-dalton doublets, there also is a 60,000-dalton protein whose synthesis is directed by 18S viral RNA from transforming virion of RSV. Peptide mapping has shown that the 60,000- and 25,000-dalton doublet are structurally related. In addition, the use of two-dimensional gel electrophoresis has allowed us to resolve both bands of the 25,000-dalton doublet into several differently charged species."}
{"id": "PMID:203939", "title": "Structural flexibility of isozyme variants: genetic variants in Drosophila disguised by cofactor and subunit binding.", "content": "Wild populations of Drosophila mojavensis exhibit considerable conformational variation in the NAD+-free form of alcohol dehydrogenase (alcohol:NAD+ oxidoreductase; EC 1.1.1.1). The variation appears genetic, as it does not occur within an inbred strain. The NAD+-bound form of alcohol dehydrogenase, present in the same individuals, does not exhibit the variation, suggesting that the binding of NAD+ acts to stabilize conformation. Such cofactor binding to enzymes may thus conceal considerable variation. A similar effect is suggested for binding of esterase subunits.", "contents": "Structural flexibility of isozyme variants: genetic variants in Drosophila disguised by cofactor and subunit binding. Wild populations of Drosophila mojavensis exhibit considerable conformational variation in the NAD+-free form of alcohol dehydrogenase (alcohol:NAD+ oxidoreductase; EC 1.1.1.1). The variation appears genetic, as it does not occur within an inbred strain. The NAD+-bound form of alcohol dehydrogenase, present in the same individuals, does not exhibit the variation, suggesting that the binding of NAD+ acts to stabilize conformation. Such cofactor binding to enzymes may thus conceal considerable variation. A similar effect is suggested for binding of esterase subunits."}
{"id": "PMID:203940", "title": "Analysis of human tumors and human malignant cell lines for BK virus-specific DNA sequences.", "content": "Most humans in the United States have been infected with BK virus (BKV), a human papovavirus. Because BKV has oncogenic properties, we have investigated whether it may be a cause of human cancer. Basic principles of tumor virology imply that BKV-induced tumors should contain BKV DNA sequences. Therefore, we assayed (by molecular hybridization) DNA from human tumors and malignant cell lines for BKV DNA, using BKV [(32)P]DNA as probe. The BKV [(32)P]DNA was labeled in vitro (nick translation) to specific activities of 1 to 2 x 10(8) cpm/mug. The BKV DNA used to prepare our probes had the properties expected of authentic BKV genomes, including density of superhelical DNA, sedimentation velocity in alkaline and neutral sucrose gradients, production of one fragment by endonuclease EcoRI cleavage and four fragments by endonuclease Hin II + III cleavage and reassociation properties. From these studies we conclude that our BKV probes hybridized well, and represented bona fide BKV DNA. Using three different BKV [(32)P]DNA probes, i.e., from three distinct plaque isolates, we have analyzed DNA from BKV-transformed cells, normal human tissues, and a large number of human tumors. All human DNAs (cell lines, normal tissues, tumors) hybridized 5% with BKV DNA. Hybridization analysis of BKV-transformed hamster cell DNA indicated 5-6 copies of at least 88% of the BKV genome per cell. No BKV DNA sequences were detected (above the normal 5% hybridization to all human DNAs) in the following normal human tissues: 10 kidney (BKV is usually isolated from urine), 3 spleen, 13 lung, 23 colon, 2 rectum, 1 ileum, and 1 skin. No BKV-specific DNA was found in 166 tumors, including 5 carcinomas (Ca) of stomach, 3 Ca small intestine, 26 Ca colon, 9 Ca rectum, 31 Ca lung, 9 adenocarcinomas and 5 oat cell carcinomas of lung, 17 melanomas, 5 Ca prostate, 4 Ca bladder, 6 Wilms tumors, 4 hypernephromas, 15 Ca kidney, 7 brain tumors, 5 Hodgkin lymphomas, 10 lymphomas (immunosuppressed patients have a high incidence of lymphomas), 2 reticulum cell sarcomas (spleen), and 3 skin tumors. We have also analyzed 7 human malignant cell lines (melanoma, lung, rhabdomyosarcoma, and glioblastomas), including several clones of a lung melanoma line; no BKV DNA sequences were detected. Because our probes could detect one copy of BKV DNA if only 10% of the cells were tumor cells, our results are very strong evidence that the tumors we analyzed did not have a BKV etiology. The tumors we tested represent about 50% of all cancers in the United States; there is no evidence that BKV is involved in the etiology of these types of tumors.", "contents": "Analysis of human tumors and human malignant cell lines for BK virus-specific DNA sequences. Most humans in the United States have been infected with BK virus (BKV), a human papovavirus. Because BKV has oncogenic properties, we have investigated whether it may be a cause of human cancer. Basic principles of tumor virology imply that BKV-induced tumors should contain BKV DNA sequences. Therefore, we assayed (by molecular hybridization) DNA from human tumors and malignant cell lines for BKV DNA, using BKV [(32)P]DNA as probe. The BKV [(32)P]DNA was labeled in vitro (nick translation) to specific activities of 1 to 2 x 10(8) cpm/mug. The BKV DNA used to prepare our probes had the properties expected of authentic BKV genomes, including density of superhelical DNA, sedimentation velocity in alkaline and neutral sucrose gradients, production of one fragment by endonuclease EcoRI cleavage and four fragments by endonuclease Hin II + III cleavage and reassociation properties. From these studies we conclude that our BKV probes hybridized well, and represented bona fide BKV DNA. Using three different BKV [(32)P]DNA probes, i.e., from three distinct plaque isolates, we have analyzed DNA from BKV-transformed cells, normal human tissues, and a large number of human tumors. All human DNAs (cell lines, normal tissues, tumors) hybridized 5% with BKV DNA. Hybridization analysis of BKV-transformed hamster cell DNA indicated 5-6 copies of at least 88% of the BKV genome per cell. No BKV DNA sequences were detected (above the normal 5% hybridization to all human DNAs) in the following normal human tissues: 10 kidney (BKV is usually isolated from urine), 3 spleen, 13 lung, 23 colon, 2 rectum, 1 ileum, and 1 skin. No BKV-specific DNA was found in 166 tumors, including 5 carcinomas (Ca) of stomach, 3 Ca small intestine, 26 Ca colon, 9 Ca rectum, 31 Ca lung, 9 adenocarcinomas and 5 oat cell carcinomas of lung, 17 melanomas, 5 Ca prostate, 4 Ca bladder, 6 Wilms tumors, 4 hypernephromas, 15 Ca kidney, 7 brain tumors, 5 Hodgkin lymphomas, 10 lymphomas (immunosuppressed patients have a high incidence of lymphomas), 2 reticulum cell sarcomas (spleen), and 3 skin tumors. We have also analyzed 7 human malignant cell lines (melanoma, lung, rhabdomyosarcoma, and glioblastomas), including several clones of a lung melanoma line; no BKV DNA sequences were detected. Because our probes could detect one copy of BKV DNA if only 10% of the cells were tumor cells, our results are very strong evidence that the tumors we analyzed did not have a BKV etiology. The tumors we tested represent about 50% of all cancers in the United States; there is no evidence that BKV is involved in the etiology of these types of tumors."}
{"id": "PMID:203941", "title": "Evidence for X-linkage of human phosphoribosylpyrophosphate synthetase.", "content": "The mode of genetic transmission of human phosphoribosylpyrophosphate synthetase (ribosephosphate pyrophosphokinase; ATP:D-ribose-5-phosphate pyrophosphotransferase; EC 2.7.6.1) was studied in fibroblasts cultured from members of a family with a structurally and electrophoretically altered phosphoribosylpyrophosphate synthetase that has increased activity per enzyme molecule. Enzyme activity in fibroblast lysates from the daughter of an affected male patient was intermediate to the activities in lysates from her father (and her affected paternal uncle) and from her mother and other normal individuals. Two bands of enzyme activity corresponding to normal and mutant phosphoribosylpyrophosphate synthetases were found in fibroblast lysates from the daughter after cellulose acetate strip electrophoresis. In contrast, only mutant enzyme was detectable in lysates derived from the male patients. Fibroblasts cloned from the daughter contained two phenotypically distinct (normal and mutant) populations of cells with respect to phosphoribosylpyrophosphate synthetase activity and electrophoretic mobility. These studies support assignment of the structural gene for human phosphoribosylpyrophosphate synthetase to the X-chromosome. No evidence for the presence of the normal enzyme was found in erythrocyte or lymphocyte lysates or in partially purified erythrocyte enzyme preparations from the heterozygous daughter, suggesting either nonrandom X-chromosome inactivation in precursors of these cells or selection against hematopoietic cells bearing the normal enzyme after random X-chromosome inactivation.", "contents": "Evidence for X-linkage of human phosphoribosylpyrophosphate synthetase. The mode of genetic transmission of human phosphoribosylpyrophosphate synthetase (ribosephosphate pyrophosphokinase; ATP:D-ribose-5-phosphate pyrophosphotransferase; EC 2.7.6.1) was studied in fibroblasts cultured from members of a family with a structurally and electrophoretically altered phosphoribosylpyrophosphate synthetase that has increased activity per enzyme molecule. Enzyme activity in fibroblast lysates from the daughter of an affected male patient was intermediate to the activities in lysates from her father (and her affected paternal uncle) and from her mother and other normal individuals. Two bands of enzyme activity corresponding to normal and mutant phosphoribosylpyrophosphate synthetases were found in fibroblast lysates from the daughter after cellulose acetate strip electrophoresis. In contrast, only mutant enzyme was detectable in lysates derived from the male patients. Fibroblasts cloned from the daughter contained two phenotypically distinct (normal and mutant) populations of cells with respect to phosphoribosylpyrophosphate synthetase activity and electrophoretic mobility. These studies support assignment of the structural gene for human phosphoribosylpyrophosphate synthetase to the X-chromosome. No evidence for the presence of the normal enzyme was found in erythrocyte or lymphocyte lysates or in partially purified erythrocyte enzyme preparations from the heterozygous daughter, suggesting either nonrandom X-chromosome inactivation in precursors of these cells or selection against hematopoietic cells bearing the normal enzyme after random X-chromosome inactivation."}
{"id": "PMID:203942", "title": "Characterization and mapping of RNase T1-resistant oligonucleotides derived from the genomes of Akv and MCF murine leukemia viruses.", "content": "T1 RNA fingerprints of the genomes of Akv-1 and Akv-2 C-type viruses are indistinguishable and oligonucleotide maps of these viruses are probably the same. Akv-1 and -2 share 55--75% of their large T1-resistant oligonucleotides with four MCF viruses isolated from AKR mice or from NIH Swiss mice that inherit either the Akv-1 or Akv-2 virus-inducing locus of AKR. The majority of Akv oligonucleotides missing from T1 fingerprints of MCFs and the majority of oligonucleotides unique to MCF viruses are clustered and  lie at corresponding positions in the 3' half of the oligonucleotide maps of Akv and MCF viruses. The RNA sequences present in different MCF isolates but not present in Akv-viruses are related. These results are consistent with a recombinational origin of MCF viruses, as proposed by Hartley and Rowe and their collaborators.", "contents": "Characterization and mapping of RNase T1-resistant oligonucleotides derived from the genomes of Akv and MCF murine leukemia viruses. T1 RNA fingerprints of the genomes of Akv-1 and Akv-2 C-type viruses are indistinguishable and oligonucleotide maps of these viruses are probably the same. Akv-1 and -2 share 55--75% of their large T1-resistant oligonucleotides with four MCF viruses isolated from AKR mice or from NIH Swiss mice that inherit either the Akv-1 or Akv-2 virus-inducing locus of AKR. The majority of Akv oligonucleotides missing from T1 fingerprints of MCFs and the majority of oligonucleotides unique to MCF viruses are clustered and  lie at corresponding positions in the 3' half of the oligonucleotide maps of Akv and MCF viruses. The RNA sequences present in different MCF isolates but not present in Akv-viruses are related. These results are consistent with a recombinational origin of MCF viruses, as proposed by Hartley and Rowe and their collaborators."}
{"id": "PMID:203943", "title": "Transcription of a defective polyoma virus genome.", "content": "The circular genome of the cloned defective polyoma virus D-50 consists of tandemly repeated copies of the DNA sequence between 67 and 84 units on the wild-type polyoma virus DNA map. Each repeated copy thus contains the origin of viral DNA replication, which is located at about 71 map units. Viral RNA was synthesized in vitro using viral transcription complexes extracted late (30 hr) after infection from mouse cells co-infected with D-50 and helper wild-type virus. Both wild-type and D-50 DNA molecules were active as templates for in vitro transcription. Approximately 84% of the RNA transcribed in vitro from wild-type DNA was complementary to the L DNA strand. This is normal for wild-type transcription late after infection. By contrast, at least 90% of the RNA transcribed from D-50 DNA molecules was complementary to the E DNA strand. After normalization of the data to account for the observed molar ratio of D-50 DNA repeated sequences to unit length wild-type DNA, we estimate that transcription of the E DNA strand of each D-50 repeated unit is about 1.4 times as efficient as transcription of the wild-type E DNA strand. Transcription of the D-50 L DNA strand, however, is only 0.03 times as efficient as transcription of the wild-type L DNA strand. The implications of these results concerning the nature and location of promoter sequences in polyoma DNA are discussed.", "contents": "Transcription of a defective polyoma virus genome. The circular genome of the cloned defective polyoma virus D-50 consists of tandemly repeated copies of the DNA sequence between 67 and 84 units on the wild-type polyoma virus DNA map. Each repeated copy thus contains the origin of viral DNA replication, which is located at about 71 map units. Viral RNA was synthesized in vitro using viral transcription complexes extracted late (30 hr) after infection from mouse cells co-infected with D-50 and helper wild-type virus. Both wild-type and D-50 DNA molecules were active as templates for in vitro transcription. Approximately 84% of the RNA transcribed in vitro from wild-type DNA was complementary to the L DNA strand. This is normal for wild-type transcription late after infection. By contrast, at least 90% of the RNA transcribed from D-50 DNA molecules was complementary to the E DNA strand. After normalization of the data to account for the observed molar ratio of D-50 DNA repeated sequences to unit length wild-type DNA, we estimate that transcription of the E DNA strand of each D-50 repeated unit is about 1.4 times as efficient as transcription of the wild-type E DNA strand. Transcription of the D-50 L DNA strand, however, is only 0.03 times as efficient as transcription of the wild-type L DNA strand. The implications of these results concerning the nature and location of promoter sequences in polyoma DNA are discussed."}
{"id": "PMID:203944", "title": "Tumor antigen(s) in cell productively infected by wild-type polyoma virus and mutant NG-18.", "content": "When isolated by means of an anti-polyoma tumor (T) antiserum, the major product from mouse cells productively infected by wild-type polyoma virus is a polypeptide of 100,000 apparent molecular weight as judged by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. In cells infected by NG-18, an hr-t mutant carrying a deletion of about 150 base pairs in the early region of the viral DNA, a T antigen species appears that comigrates with that of the wild-type virus. Comparisons of peptides after partial proteolysis reveal no differences between mutant and wild-type products. Both wild-type and mutant 100,000 products can be labeled in vivo with [(32)P]orthophosphate. An independent and more reliable estimate of the molecular weight of this protein using guanidine/Sepharose chromatography yields a value of 81,000 for both mutant and wild-type species. The apparent identity of wild-type and mutant products indicates that the deletion in NG-18 lies outside of the region encoding this major T antigen species. Immunoprecipitates from wild-type infected cells shows four bands in addition to the \"100,000\" band; these have apparent molecular weights of 63,000, 56,000, 36,000, and 22,000 by sodium dodecyl sulfate/polyacrylamide gel electrophoresis; the 56,000 and 36,000 species are phosphorylated. All four of these lower molecular weight bands are absent or drastically reduced in the immunoprecipitates from NG-18-infected cells.", "contents": "Tumor antigen(s) in cell productively infected by wild-type polyoma virus and mutant NG-18. When isolated by means of an anti-polyoma tumor (T) antiserum, the major product from mouse cells productively infected by wild-type polyoma virus is a polypeptide of 100,000 apparent molecular weight as judged by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. In cells infected by NG-18, an hr-t mutant carrying a deletion of about 150 base pairs in the early region of the viral DNA, a T antigen species appears that comigrates with that of the wild-type virus. Comparisons of peptides after partial proteolysis reveal no differences between mutant and wild-type products. Both wild-type and mutant 100,000 products can be labeled in vivo with [(32)P]orthophosphate. An independent and more reliable estimate of the molecular weight of this protein using guanidine/Sepharose chromatography yields a value of 81,000 for both mutant and wild-type species. The apparent identity of wild-type and mutant products indicates that the deletion in NG-18 lies outside of the region encoding this major T antigen species. Immunoprecipitates from wild-type infected cells shows four bands in addition to the \"100,000\" band; these have apparent molecular weights of 63,000, 56,000, 36,000, and 22,000 by sodium dodecyl sulfate/polyacrylamide gel electrophoresis; the 56,000 and 36,000 species are phosphorylated. All four of these lower molecular weight bands are absent or drastically reduced in the immunoprecipitates from NG-18-infected cells."}
{"id": "PMID:203945", "title": "Gonadotropin binding and stimulation of steroidogenesis in Leydig tumor cells.", "content": "Testicular tumors are generally characterized by a loss of responsiveness to gonadotropins. The M5480 Leydig cell tumor is unusual, if not unique, in that it responds to human choriogonadotropin and to lutropin via increased steroidogenesis. This report describes the identification of two variants of the original M5480 tumor that have altered steroid output both in the basal state and in response to human choriogonadotropin. One of the tumors produces mainly progesterone, which is stimulated by the choriogonadotropin; the other tumor produces about equal amounts of progesterone and testosterone, and the secretion of both is stimulated by the choriogonadotropin. The dissociation constant describing the interaction between Leydig tumor cells and (125)I-labeled human choriogonadotropin is between 3 and 5x10(-11) M. This agrees with values reported for normal Leydig cells, although the tumor cells appear to have fewer receptors. The differences noted in the two tumors and normal Leydig cells may have arisen from alterations in gene regulation, or in mutations, involving one or more enzymes in the pathway in which progesterone is converted to testosterone. Under the experimental conditions used, all the tumors studied (seven generations) responded to the choriogonadotropin both in binding and in the resultant stimulation of steroidogenesis. This property, together with the characteristic that a homogeneous cell population can be obtained without enzymatic treatment, should qualify the M5480 Leydig cell tumor(s) as a model system for further studies on the mechanism of action of gonadotropin, on hormone receptors, and on hormonally responsive tumors.", "contents": "Gonadotropin binding and stimulation of steroidogenesis in Leydig tumor cells. Testicular tumors are generally characterized by a loss of responsiveness to gonadotropins. The M5480 Leydig cell tumor is unusual, if not unique, in that it responds to human choriogonadotropin and to lutropin via increased steroidogenesis. This report describes the identification of two variants of the original M5480 tumor that have altered steroid output both in the basal state and in response to human choriogonadotropin. One of the tumors produces mainly progesterone, which is stimulated by the choriogonadotropin; the other tumor produces about equal amounts of progesterone and testosterone, and the secretion of both is stimulated by the choriogonadotropin. The dissociation constant describing the interaction between Leydig tumor cells and (125)I-labeled human choriogonadotropin is between 3 and 5x10(-11) M. This agrees with values reported for normal Leydig cells, although the tumor cells appear to have fewer receptors. The differences noted in the two tumors and normal Leydig cells may have arisen from alterations in gene regulation, or in mutations, involving one or more enzymes in the pathway in which progesterone is converted to testosterone. Under the experimental conditions used, all the tumors studied (seven generations) responded to the choriogonadotropin both in binding and in the resultant stimulation of steroidogenesis. This property, together with the characteristic that a homogeneous cell population can be obtained without enzymatic treatment, should qualify the M5480 Leydig cell tumor(s) as a model system for further studies on the mechanism of action of gonadotropin, on hormone receptors, and on hormonally responsive tumors."}
{"id": "PMID:203946", "title": "Nutritional agents which affect metabolic zinc status.", "content": "As the number of factors which affect zinc absorption and homeostasis increase, it becomes more apparent that the relative zinc status of the population cannot be estimated from the analyzed zinc content of foods. The environment of the small intestine at the time of absorption can only be estimated from the diet fed. Even then since both endogenous and exogenous factors determine the zinc absorbed, the precision of these estimations should allow for large individual variation.", "contents": "Nutritional agents which affect metabolic zinc status. As the number of factors which affect zinc absorption and homeostasis increase, it becomes more apparent that the relative zinc status of the population cannot be estimated from the analyzed zinc content of foods. The environment of the small intestine at the time of absorption can only be estimated from the diet fed. Even then since both endogenous and exogenous factors determine the zinc absorbed, the precision of these estimations should allow for large individual variation."}
{"id": "PMID:203947", "title": "Central catecholamine and peripheral noradrenaline depletion: effects on one-way trace-conditioning.", "content": "The present study evaluated the differential contributions of the central and peripheral catecholaminergic systems in aversive learning using trace-conditioning procedure. Twenty-seven male Wistar rats were randomly assigned to one of the three groups: central drug and peripheral saline (CDPS) injections, central saline and peripheral drug (CSPD) injections, and central saline and peripheral saline (CSPS) injections. Results showed that: (1) the rate of acquisition and the overall avoidance responses for the drug treated groups was significantly poorer than the control group; (2) there was no significant difference in performance between the two drug treated groups; and, (3) neither central nor peripheral catecholamine depletion had a significant effect on the secretion of plasma corticosterone. The findings failed to confirm the hypotheses (1) that central CA depletion is more detrimental than peripheral NA depletion, (2) that plasma 11-OHCS plays a mediating role in the acquisition of avoidance and escape responses in rats depleted of catecholaminergic systems.", "contents": "Central catecholamine and peripheral noradrenaline depletion: effects on one-way trace-conditioning. The present study evaluated the differential contributions of the central and peripheral catecholaminergic systems in aversive learning using trace-conditioning procedure. Twenty-seven male Wistar rats were randomly assigned to one of the three groups: central drug and peripheral saline (CDPS) injections, central saline and peripheral drug (CSPD) injections, and central saline and peripheral saline (CSPS) injections. Results showed that: (1) the rate of acquisition and the overall avoidance responses for the drug treated groups was significantly poorer than the control group; (2) there was no significant difference in performance between the two drug treated groups; and, (3) neither central nor peripheral catecholamine depletion had a significant effect on the secretion of plasma corticosterone. The findings failed to confirm the hypotheses (1) that central CA depletion is more detrimental than peripheral NA depletion, (2) that plasma 11-OHCS plays a mediating role in the acquisition of avoidance and escape responses in rats depleted of catecholaminergic systems."}
{"id": "PMID:203948", "title": "On the mechanism of renin release by restraint stress in rats.", "content": "Restraint causes an increase in plasma renin activity (PRA) which is not affected by pretreatment with dl-propranolo (1 mg/kg IP) or sotalol (15 mg/kg IP). These doses of beta-adrenergic blocking agents are effective in suppressing the stimulation of PRA by isoproterenol. Large doses of dl-propranolol (10 mg/kg IP) and d-propranolol (5 mg/kg IP) attenuate the restraint-induced PRA increase. Adrenal demedullectomy does not affect the PRA response to restraint. Renal denervation blunts the PRA rise due to restraint, but not to direct stimulation by the beta-adrenergic agonist, isoproterenol. It is concluded that the increase in PRA during restraint stress in rats is not solely dependent on an intact renal sympathetic innervation. A significant portion of this stress-induced PRA increase appears to involve a non-adrenergic mechanism.", "contents": "On the mechanism of renin release by restraint stress in rats. Restraint causes an increase in plasma renin activity (PRA) which is not affected by pretreatment with dl-propranolo (1 mg/kg IP) or sotalol (15 mg/kg IP). These doses of beta-adrenergic blocking agents are effective in suppressing the stimulation of PRA by isoproterenol. Large doses of dl-propranolol (10 mg/kg IP) and d-propranolol (5 mg/kg IP) attenuate the restraint-induced PRA increase. Adrenal demedullectomy does not affect the PRA response to restraint. Renal denervation blunts the PRA rise due to restraint, but not to direct stimulation by the beta-adrenergic agonist, isoproterenol. It is concluded that the increase in PRA during restraint stress in rats is not solely dependent on an intact renal sympathetic innervation. A significant portion of this stress-induced PRA increase appears to involve a non-adrenergic mechanism."}
{"id": "PMID:203950", "title": "Morphine-induced tail erection: site of action.", "content": "Acute ablation techniques were used to localize morphine-induced tail erection (MITE) within the central nervous system of mice. Morphine produced no elevation of tails in mice whose spinal cord had been transected at the lower thoracic or lumbar levels. Decortication and high-level precollicular decerebration did not prevent MITE while morphine caused no tail response at all in low-level inferior collicular decerebrate mice. Lesions in various portions of the mesencephalon revealed that the degree of MITE was closely related to the size of the lesions of the central gray matter. The larger the lesion, the smaller the degree of tail elevation. MITE could not be elicited in mice when the mesencephalic central gray matter had been completely destroyed. Results indicate that morphine acts on the mesencephalic central gray matter producing tail erection and the pathway responsible for the reaction descends from the midbrain downward to the spinal cord.", "contents": "Morphine-induced tail erection: site of action. Acute ablation techniques were used to localize morphine-induced tail erection (MITE) within the central nervous system of mice. Morphine produced no elevation of tails in mice whose spinal cord had been transected at the lower thoracic or lumbar levels. Decortication and high-level precollicular decerebration did not prevent MITE while morphine caused no tail response at all in low-level inferior collicular decerebrate mice. Lesions in various portions of the mesencephalon revealed that the degree of MITE was closely related to the size of the lesions of the central gray matter. The larger the lesion, the smaller the degree of tail elevation. MITE could not be elicited in mice when the mesencephalic central gray matter had been completely destroyed. Results indicate that morphine acts on the mesencephalic central gray matter producing tail erection and the pathway responsible for the reaction descends from the midbrain downward to the spinal cord."}
{"id": "PMID:203951", "title": "Cortical EEG power spectra associated with sleep-awake behavior in the rat.", "content": "Power spectral analyses were used to study cortical EEG activities during sleep-awake behavior in the rat. EEG spectra, both long-time and sequential short-time, derived from EEG during the states of wakefulness, sleep, and REM sleep were qualitatively and quantitatively different. The degree of inter- and intrasubject variability between these spectra was minimal. This experimental model with the rat should allow quantitative delineation of cortical EEG changes produced by psychotropic drugs.", "contents": "Cortical EEG power spectra associated with sleep-awake behavior in the rat. Power spectral analyses were used to study cortical EEG activities during sleep-awake behavior in the rat. EEG spectra, both long-time and sequential short-time, derived from EEG during the states of wakefulness, sleep, and REM sleep were qualitatively and quantitatively different. The degree of inter- and intrasubject variability between these spectra was minimal. This experimental model with the rat should allow quantitative delineation of cortical EEG changes produced by psychotropic drugs."}
{"id": "PMID:203958", "title": "Baseline sleep-wake patterns in the pointer dog.", "content": "The 24-hr electrographic patterns (EEG, EOG, EMG) of six normal pointer dogs were recorded in a laboratory setting. Two states of sleep (slow-wave and rapid eye movement) and wakefulness (alert and drowsy) were identified. The total recording period comprised 44% of alert wakefulness, 21% of the drowsy state, while slow-wave sleep occupied 23% and REM sleep 12% of the time. The mean length of a REM sleep episode averaged 6 min and the mean REM sleep cycle was 20 min. The mean polycyclic sleep-wake cycle was 83 min. Sleep episodes averaged 45 min and the mean waking episode was 38 min. There was an average of two REM sleep episodes per sleep-wake cycle. The dog has a propensity to sleep over a 16-hr interval from 1300 to 0500 but the most sleep occurred between 2100 and 0400 hr during darkness.", "contents": "Baseline sleep-wake patterns in the pointer dog. The 24-hr electrographic patterns (EEG, EOG, EMG) of six normal pointer dogs were recorded in a laboratory setting. Two states of sleep (slow-wave and rapid eye movement) and wakefulness (alert and drowsy) were identified. The total recording period comprised 44% of alert wakefulness, 21% of the drowsy state, while slow-wave sleep occupied 23% and REM sleep 12% of the time. The mean length of a REM sleep episode averaged 6 min and the mean REM sleep cycle was 20 min. The mean polycyclic sleep-wake cycle was 83 min. Sleep episodes averaged 45 min and the mean waking episode was 38 min. There was an average of two REM sleep episodes per sleep-wake cycle. The dog has a propensity to sleep over a 16-hr interval from 1300 to 0500 but the most sleep occurred between 2100 and 0400 hr during darkness."}
{"id": "PMID:203959", "title": "Sleep induced by intestinal stimulation in cats.", "content": "The influence of afferent impulses of intestinal origin on the sleep stages was studied in fed and starved cats. Low-frequency electrical stimulation of the mucosal surface in a small intestinal fistula reduced the latency of sleep onset. The number of slow wave sleep episodes decreased, but their mean duration increased during stimulation. Conversely, the number of paradoxical sleep episodes increased, but their mean duration was not significantly modified by the intestinal stimulation. The role of viscerosensory events in the control of sleep is discussed in relationship to these results.", "contents": "Sleep induced by intestinal stimulation in cats. The influence of afferent impulses of intestinal origin on the sleep stages was studied in fed and starved cats. Low-frequency electrical stimulation of the mucosal surface in a small intestinal fistula reduced the latency of sleep onset. The number of slow wave sleep episodes decreased, but their mean duration increased during stimulation. Conversely, the number of paradoxical sleep episodes increased, but their mean duration was not significantly modified by the intestinal stimulation. The role of viscerosensory events in the control of sleep is discussed in relationship to these results."}
{"id": "PMID:203960", "title": "Two preliminary studies on sleep and psychotherapy.", "content": "Two preliminary studies were conducted to assess the effects of an intensive outpatient psychotherapy, Feeling Therapy, on sleep. This therapy was chosen because of its demonstrated ability to affect its patients' dreams. In the first study a newly entering female patient was recorded across the first three weeks of intensive daily therapy. In contrast to two control subjects recorded across a similar time period, she demonstrated low REM times and short REM latencies on the average, and considerably greater variability in nearly every parameter. In the second study, two patients were recorded across three days (the middle of which was the day of a therapy session) first when new in therapy and then again after two and one-half years of therapy. It was found that when new in therapy both subjects spent nights of significantly altered sleep the day of the therapy session. One subject showed no REM sleep whatsoever while the other showed a 10 min REM latency and low REM time. The significance of these findings and the direction of future research is discussed.", "contents": "Two preliminary studies on sleep and psychotherapy. Two preliminary studies were conducted to assess the effects of an intensive outpatient psychotherapy, Feeling Therapy, on sleep. This therapy was chosen because of its demonstrated ability to affect its patients' dreams. In the first study a newly entering female patient was recorded across the first three weeks of intensive daily therapy. In contrast to two control subjects recorded across a similar time period, she demonstrated low REM times and short REM latencies on the average, and considerably greater variability in nearly every parameter. In the second study, two patients were recorded across three days (the middle of which was the day of a therapy session) first when new in therapy and then again after two and one-half years of therapy. It was found that when new in therapy both subjects spent nights of significantly altered sleep the day of the therapy session. One subject showed no REM sleep whatsoever while the other showed a 10 min REM latency and low REM time. The significance of these findings and the direction of future research is discussed."}
{"id": "PMID:203961", "title": "Failure of interocular transfer in the pigeon (Columba livia).", "content": "Pigeons were trained on a modified jumping stand to discriminate a circle from a triangle using only one eye. Testing with the naive eye revealed no evidence of interocular transfer. This failure of transfer was also observed under more stringent testing using reversal learning. The results are discussed in terms of a selective attention model for panoramic vision.", "contents": "Failure of interocular transfer in the pigeon (Columba livia). Pigeons were trained on a modified jumping stand to discriminate a circle from a triangle using only one eye. Testing with the naive eye revealed no evidence of interocular transfer. This failure of transfer was also observed under more stringent testing using reversal learning. The results are discussed in terms of a selective attention model for panoramic vision."}
{"id": "PMID:203962", "title": "Ulcer reduction by non-nutritive bulk in pylorus ligated rats.", "content": "The effects of solid non-nutritive diet on pylorus-ligation ulcers were tested. An experimental group of 16 rats received a bulky mixture of silica and methylcellulose during 48 hr prior to ligation. Control rats were food deprived for the same period of time. A multivariate analysis of variance was applied to nine measures of the study. It was found that rumenal ulceration and total acidity were lower in experimental animals than in controls. This finding confirms a previous observation indicating that the physical property of diet has antiulcerogenic effects.", "contents": "Ulcer reduction by non-nutritive bulk in pylorus ligated rats. The effects of solid non-nutritive diet on pylorus-ligation ulcers were tested. An experimental group of 16 rats received a bulky mixture of silica and methylcellulose during 48 hr prior to ligation. Control rats were food deprived for the same period of time. A multivariate analysis of variance was applied to nine measures of the study. It was found that rumenal ulceration and total acidity were lower in experimental animals than in controls. This finding confirms a previous observation indicating that the physical property of diet has antiulcerogenic effects."}
{"id": "PMID:203963", "title": "[Phasic activity in rats].", "content": "At the central level, in the rat, phasic activity has been recorded during paradoxical sleep and in acute conditions after injection of reserpine or parachlorophenylalanine. At the external level, during paradoxical sleep, the extraocular muscles lateral rectus, superior rectus and superior oblique are activated in both plastic and tonic manners. The muscles of the whiskers are also activated; these muscular activations are more often than not synchronous with the eye movements (80%). The time distribution of these ocular movements is homogenous. Reserpine induces phasic muscular activations of the extraocular muscles.", "contents": "[Phasic activity in rats]. At the central level, in the rat, phasic activity has been recorded during paradoxical sleep and in acute conditions after injection of reserpine or parachlorophenylalanine. At the external level, during paradoxical sleep, the extraocular muscles lateral rectus, superior rectus and superior oblique are activated in both plastic and tonic manners. The muscles of the whiskers are also activated; these muscular activations are more often than not synchronous with the eye movements (80%). The time distribution of these ocular movements is homogenous. Reserpine induces phasic muscular activations of the extraocular muscles."}
{"id": "PMID:203965", "title": "Ulnar artery thrombosis.", "content": "Forty-six patients with ulnar artery thrombosis were evaluated. A comparison of the results was made between those patients who were treated by sympathectomy and those in whom we attempted to reestablish the blood flow. A reverse vein graft was often used in the latter group. Based on the results of this study, we believe the preferred method of treatment for ulnar artery thrombosis is an attempt at the reestablishment of blood flow.", "contents": "Ulnar artery thrombosis. Forty-six patients with ulnar artery thrombosis were evaluated. A comparison of the results was made between those patients who were treated by sympathectomy and those in whom we attempted to reestablish the blood flow. A reverse vein graft was often used in the latter group. Based on the results of this study, we believe the preferred method of treatment for ulnar artery thrombosis is an attempt at the reestablishment of blood flow."}
{"id": "PMID:203968", "title": "A psychophysiological investigation of the long-term effects of clozapine upon sleep patterns of normal young adults.", "content": "A 25-night single-blind cross over design was employed to determine the long-term effects of clozapine on the sleep patterns of six normal young adults. Subjects received 12.50 mg placebo on the first and last five nights, whereas on the intermediate 15 nights 12.5 mg clozapine was administered. The subjects slept in the laboratory on the third and fourth nights to obtain baseline recordings, and on the eight, twelfth, sixteenth, and twentieth nights to determine the effects of clozapine on sleep variables. Recordings on nights 21 and 25 were used to assess withdrawal effects. Percentage stage 1 sleep and indices of body movements during sleep were significantly reduced, suggesting that clozapine may have sleep-inducing properties. There were no significant rebound of stage REM sleep during drug withdrawal despite a small but significant reduction in stage REM during drug administration. Numerous side effects, indicative of sleepiness, were reported on the mornings following drug administration, and there was evidence of a rapid tolerance to clozapine. These findings may limit the efficacy of clozapine as an hypnotic agent over an extended period of time. Further research on insomniac subjects is therefore indicated.", "contents": "A psychophysiological investigation of the long-term effects of clozapine upon sleep patterns of normal young adults. A 25-night single-blind cross over design was employed to determine the long-term effects of clozapine on the sleep patterns of six normal young adults. Subjects received 12.50 mg placebo on the first and last five nights, whereas on the intermediate 15 nights 12.5 mg clozapine was administered. The subjects slept in the laboratory on the third and fourth nights to obtain baseline recordings, and on the eight, twelfth, sixteenth, and twentieth nights to determine the effects of clozapine on sleep variables. Recordings on nights 21 and 25 were used to assess withdrawal effects. Percentage stage 1 sleep and indices of body movements during sleep were significantly reduced, suggesting that clozapine may have sleep-inducing properties. There were no significant rebound of stage REM sleep during drug withdrawal despite a small but significant reduction in stage REM during drug administration. Numerous side effects, indicative of sleepiness, were reported on the mornings following drug administration, and there was evidence of a rapid tolerance to clozapine. These findings may limit the efficacy of clozapine as an hypnotic agent over an extended period of time. Further research on insomniac subjects is therefore indicated."}
{"id": "PMID:203976", "title": "Screening of a family for chemodectoma.", "content": "59 relatives with a family history of hereditary chemodectoma have been successfully screened by means of radionuclide scintiangiography. The findings showed a close correlation with selective roentgenangiography. 3 asymptomatic patients with chemodectoma were revealed by these methods without causing discomfort to the group involved.", "contents": "Screening of a family for chemodectoma. 59 relatives with a family history of hereditary chemodectoma have been successfully screened by means of radionuclide scintiangiography. The findings showed a close correlation with selective roentgenangiography. 3 asymptomatic patients with chemodectoma were revealed by these methods without causing discomfort to the group involved."}
{"id": "PMID:203978", "title": "Diagnosis of juvenile angiofibroma by computed tomography.", "content": "Computed tomography (CT) accurately localized juvenile angiofibromata in 3 patients. The expanded pterygopalatine fossa and canal were visualized by CT in all three cases. Because of the hemorrhagic tendency of these tumors, a noninvasive modality such as CT is especially valuable in planning therapy.", "contents": "Diagnosis of juvenile angiofibroma by computed tomography. Computed tomography (CT) accurately localized juvenile angiofibromata in 3 patients. The expanded pterygopalatine fossa and canal were visualized by CT in all three cases. Because of the hemorrhagic tendency of these tumors, a noninvasive modality such as CT is especially valuable in planning therapy."}
{"id": "PMID:203979", "title": "99mTc-pyrophosphate imaging in acute pericarditis: a clinical and experimental study.", "content": "Fifteen patients with clinical and electrocardiographic features of acute pericarditis underwent myocardial scintigraphy using 99mTc-pyrophosphate. All had normal images. In 5 additional patients with acute pericarditis and evidence of ischemic heart disease, 99mTc-pyrophosphate images showed focal abnormalities in 2 patients and equivocal findings in 2. Serial myocardial radionuclide images were obtained 2 to 18 days after induction of pericarditis in 8 dogs; all images were normal. No stainable tissue calcium was demonstrated histochemically in the pericardium or myocardium of these dogs. Our results suggest that 99mTc-PYP myocardial radionuclide images are normal in acute pericarditis in the absence of ischemic heart disease.", "contents": "99mTc-pyrophosphate imaging in acute pericarditis: a clinical and experimental study. Fifteen patients with clinical and electrocardiographic features of acute pericarditis underwent myocardial scintigraphy using 99mTc-pyrophosphate. All had normal images. In 5 additional patients with acute pericarditis and evidence of ischemic heart disease, 99mTc-pyrophosphate images showed focal abnormalities in 2 patients and equivocal findings in 2. Serial myocardial radionuclide images were obtained 2 to 18 days after induction of pericarditis in 8 dogs; all images were normal. No stainable tissue calcium was demonstrated histochemically in the pericardium or myocardium of these dogs. Our results suggest that 99mTc-PYP myocardial radionuclide images are normal in acute pericarditis in the absence of ischemic heart disease."}
{"id": "PMID:203980", "title": "Thallium-201 distribution in the thyroid: relationship to thyroidal trapping function.", "content": "Experiments were undertaken to determine the behavior of thallium-201 in the thyroid in relation to the iodide-trapping mechanism in rats. Iodide trapping was compared to thyroidal thallium-201 trapping 30 minutes after intravenous injection. Thallium-201 uptake followed iodide uptake in control rats. TSH- and T3-treated rats but did not decrease in the same manner as iodide concentration in perchlorate-treated rats. These studies suggest that thallium-201 distribution in the thyroid may reflect the cationic side of the iodide pump or possible thyroidal blood flow.", "contents": "Thallium-201 distribution in the thyroid: relationship to thyroidal trapping function. Experiments were undertaken to determine the behavior of thallium-201 in the thyroid in relation to the iodide-trapping mechanism in rats. Iodide trapping was compared to thyroidal thallium-201 trapping 30 minutes after intravenous injection. Thallium-201 uptake followed iodide uptake in control rats. TSH- and T3-treated rats but did not decrease in the same manner as iodide concentration in perchlorate-treated rats. These studies suggest that thallium-201 distribution in the thyroid may reflect the cationic side of the iodide pump or possible thyroidal blood flow."}
{"id": "PMID:203981", "title": "Dibutryl cyclic adenosine monophosphate: effect on radiosensitivity of tumors and normal tissues in mice.", "content": "The effect of dibutryl cyclic adenosine monophosphate (db-cAMP, 30 mg/kg), injected into mice before irradiation, on the radiation sensitivity of various tissues was investigated. Survival of proliferating hair follicles, small gut stem cells, fibrosarcoma (FSa) micrometastases in the lungs, and two different mammary carcinomas, as assayed by the TCD50 method, were studied. Intraperitoneal injection of db-cAMP before irradiation resulted in higher survival of hair follicles irradiated on the third day after plucking. Stem cells in the small gut showed increased survival if irradiated 4 hours after injection. There was no effect on the survival of FSa micrometastases by preinjection and the TCD50/120 days of the mammary carcinomas was not altered.", "contents": "Dibutryl cyclic adenosine monophosphate: effect on radiosensitivity of tumors and normal tissues in mice. The effect of dibutryl cyclic adenosine monophosphate (db-cAMP, 30 mg/kg), injected into mice before irradiation, on the radiation sensitivity of various tissues was investigated. Survival of proliferating hair follicles, small gut stem cells, fibrosarcoma (FSa) micrometastases in the lungs, and two different mammary carcinomas, as assayed by the TCD50 method, were studied. Intraperitoneal injection of db-cAMP before irradiation resulted in higher survival of hair follicles irradiated on the third day after plucking. Stem cells in the small gut showed increased survival if irradiated 4 hours after injection. There was no effect on the survival of FSa micrometastases by preinjection and the TCD50/120 days of the mammary carcinomas was not altered."}
{"id": "PMID:203986", "title": "The isolation of adenoviruses from goats affected with peste des petits ruminants in Nigeria.", "content": "Mucosal scrapings from the large intestine of two goats that had died from peste des petits ruminants (PPR) in separate outbreaks in Nigeria were examined for viruses. A mixed viral infection of PPR virus (morbillivirus) and adenovirus was confirmed in both goats. The adenoviruses did not conform to any of the ovine and bovine serotypes recognised; the two isolates were considered different serotypes. It is concluded that, although the role of adenoviruses in the epizootiology of PPR in Nigeria is difficult to appraise, they are probably commensals. This is believed to be the first report of the isolation of adenoviruses from goats.", "contents": "The isolation of adenoviruses from goats affected with peste des petits ruminants in Nigeria. Mucosal scrapings from the large intestine of two goats that had died from peste des petits ruminants (PPR) in separate outbreaks in Nigeria were examined for viruses. A mixed viral infection of PPR virus (morbillivirus) and adenovirus was confirmed in both goats. The adenoviruses did not conform to any of the ovine and bovine serotypes recognised; the two isolates were considered different serotypes. It is concluded that, although the role of adenoviruses in the epizootiology of PPR in Nigeria is difficult to appraise, they are probably commensals. This is believed to be the first report of the isolation of adenoviruses from goats."}
{"id": "PMID:203987", "title": "Isolation of avian infectious bronchitis virus from experimentally infected chickens.", "content": "Virus was recovered from the faeces of chickens infected at three or four weeks of age for more than 20 weeks after infection with commercial vaccines or with the T strain of avian infectious bronchitis virus (IBV). Virus was not recovered from the trachea, liver, spleen, bursa or kidneys of T strain infected birds longer than 29 days after infection at which point IBV was recovered from the bursa of a single infected bird. In a subsequent experiment IBV was recovered from the caecal lymph nodes and faeces of one of five birds 14 weeks after infection with a commercial vaccine but no virus was isolated from the trachea, kidneys, duodenum, bursa, ovaries or testes of any of the five birds at this time.", "contents": "Isolation of avian infectious bronchitis virus from experimentally infected chickens. Virus was recovered from the faeces of chickens infected at three or four weeks of age for more than 20 weeks after infection with commercial vaccines or with the T strain of avian infectious bronchitis virus (IBV). Virus was not recovered from the trachea, liver, spleen, bursa or kidneys of T strain infected birds longer than 29 days after infection at which point IBV was recovered from the bursa of a single infected bird. In a subsequent experiment IBV was recovered from the caecal lymph nodes and faeces of one of five birds 14 weeks after infection with a commercial vaccine but no virus was isolated from the trachea, kidneys, duodenum, bursa, ovaries or testes of any of the five birds at this time."}
{"id": "PMID:203988", "title": "Subclinical pneumonia associated with an experimental adenovirus infection in the domestic fowl and the effect of concurrent infectious laryngotracheitis virus.", "content": "A CELO-type adenovirus (AV) isolated from fowls with respiratory disease was inoculated experimentally into the tracheas of young birds. No symptoms referable to respiratory infection were evident. Post mortem examination between days 2 and 5 after inoculation revealed pneumonia involving up to 30 per cent of the surface of the lungs. Histologically, a focal to diffuse interstitial lymphocytic infiltration and bronchiolar degeneration were present. Concurrent infections with a mild strain of infectious laryngotracheitis virus (ILT) failed to enhance the pathogenicity of either the AV or ILT infections.", "contents": "Subclinical pneumonia associated with an experimental adenovirus infection in the domestic fowl and the effect of concurrent infectious laryngotracheitis virus. A CELO-type adenovirus (AV) isolated from fowls with respiratory disease was inoculated experimentally into the tracheas of young birds. No symptoms referable to respiratory infection were evident. Post mortem examination between days 2 and 5 after inoculation revealed pneumonia involving up to 30 per cent of the surface of the lungs. Histologically, a focal to diffuse interstitial lymphocytic infiltration and bronchiolar degeneration were present. Concurrent infections with a mild strain of infectious laryngotracheitis virus (ILT) failed to enhance the pathogenicity of either the AV or ILT infections."}
{"id": "PMID:203989", "title": "Lack of maedi viral related RNA in pulmonary carcinoma of sheep (jaagsiekte).", "content": "Molecular hybridisation with radioactively labelled DNA complementary to the RNA of the maedi virus was used to probe for homologous RNA in the polysome fraction of pulmonary carcinomas (jaagiekte) of Awassi sheep. No sequence homology was detected, which suggests that maedi (or visna) virus is not implicated in the aetiology of pulmonary carcinoma of sheep.", "contents": "Lack of maedi viral related RNA in pulmonary carcinoma of sheep (jaagsiekte). Molecular hybridisation with radioactively labelled DNA complementary to the RNA of the maedi virus was used to probe for homologous RNA in the polysome fraction of pulmonary carcinomas (jaagiekte) of Awassi sheep. No sequence homology was detected, which suggests that maedi (or visna) virus is not implicated in the aetiology of pulmonary carcinoma of sheep."}
{"id": "PMID:203990", "title": "Serological studies of mucosal disease virus in England and Wales.", "content": "A survey of the cattle population in England and Wales showed that about 62 per cent of animals had neutralising (SN) antibody to BVD-MD virus in their serum. Fewer seropositive individuals were detected by immunodiffusion (53 per cent), and complement fixation (CF) tests (34 per cent). The prevalence of antibody was not affected by herd size, but some variation was found between various regions of the country, and the proportion of animals seropositive rose markedly with age. The immunodiffusion test was a specific but relatively insensitive method of detecting antibody compared with the SN test. The data suggest that the CF test may detect a different, short-lived antibody. For diagnostic serology, the SN test was superior to the other methods. No antibody to the virus was detected in human or equine sera but about 7.3 per cent of sheep sampled had serum antibody to the virus in the immunodiffusion test.", "contents": "Serological studies of mucosal disease virus in England and Wales. A survey of the cattle population in England and Wales showed that about 62 per cent of animals had neutralising (SN) antibody to BVD-MD virus in their serum. Fewer seropositive individuals were detected by immunodiffusion (53 per cent), and complement fixation (CF) tests (34 per cent). The prevalence of antibody was not affected by herd size, but some variation was found between various regions of the country, and the proportion of animals seropositive rose markedly with age. The immunodiffusion test was a specific but relatively insensitive method of detecting antibody compared with the SN test. The data suggest that the CF test may detect a different, short-lived antibody. For diagnostic serology, the SN test was superior to the other methods. No antibody to the virus was detected in human or equine sera but about 7.3 per cent of sheep sampled had serum antibody to the virus in the immunodiffusion test."}
{"id": "PMID:203997", "title": "Increased serum gastrin concentration in hemodialysis patients treated with 1-alpha-hydroxy vitamin D.", "content": "Serum gastrin and serum calcium concentrations were measured in 9 hemodialysis patients treated with 1-alpha-hydroxy vitamin D3 and in 15 control patients. Serum calcium and serum gastrin concentrations were significantly increased after 1 and after 5 months of treatment with 1-alpha-hydroxy vitamin D3. It is concluded that serum gastrin concentration is sensitive to a rise in calcium concentration within physiological range in patients with chronic renal failure.", "contents": "Increased serum gastrin concentration in hemodialysis patients treated with 1-alpha-hydroxy vitamin D. Serum gastrin and serum calcium concentrations were measured in 9 hemodialysis patients treated with 1-alpha-hydroxy vitamin D3 and in 15 control patients. Serum calcium and serum gastrin concentrations were significantly increased after 1 and after 5 months of treatment with 1-alpha-hydroxy vitamin D3. It is concluded that serum gastrin concentration is sensitive to a rise in calcium concentration within physiological range in patients with chronic renal failure."}
{"id": "PMID:203998", "title": "A controlled comparison of corticotropin and hydrocortisone in the treatment of severe proctocolitis.", "content": "A randomized controlled trial has been made of corticotropin (ACTH) 80 units given intramuscularly daily and hydrocortisone 400 mg infused intravenously over 24 hours, in the treatment of in-patients with severe proctocolitis. Seven patients were treated with ACTH and nine with hydrocortisone over an initial seven days. Three patients in the ACTH group and six in the hydrocortisone group improved and were discharged on medical treatment. Four patients treated with ACTH and two with hydrocortisone required urgent colectomy during this admission. Plasma cortisol levels were measured, but there was no correlation between these and the observed therapeutic response. Sideeffects were troublesome in both groups but were more marked in those treated with hydrocortisone. It is concluded that ACTH is not intrinsically superior to hydrocortisone in these doses, in the treatment of severe proctocolitis.", "contents": "A controlled comparison of corticotropin and hydrocortisone in the treatment of severe proctocolitis. A randomized controlled trial has been made of corticotropin (ACTH) 80 units given intramuscularly daily and hydrocortisone 400 mg infused intravenously over 24 hours, in the treatment of in-patients with severe proctocolitis. Seven patients were treated with ACTH and nine with hydrocortisone over an initial seven days. Three patients in the ACTH group and six in the hydrocortisone group improved and were discharged on medical treatment. Four patients treated with ACTH and two with hydrocortisone required urgent colectomy during this admission. Plasma cortisol levels were measured, but there was no correlation between these and the observed therapeutic response. Sideeffects were troublesome in both groups but were more marked in those treated with hydrocortisone. It is concluded that ACTH is not intrinsically superior to hydrocortisone in these doses, in the treatment of severe proctocolitis."}
{"id": "PMID:203999", "title": "Human leukocyte migration inhibitory factor (LIF). IV. 3',5'-cGMP protects LIF against inactivation by the esterase inhibitor phenylmethylsulfonyl fluoride.", "content": "Recently reported experiments suggest that human leukocyte migration inhibitory factor (LIF) has properties of an esterase and a protease with substrate specificities directed against arginine esters and amides. Also reported previously, the synthetic phosphodiester bis-p-nitrophenyl phosphate (BNPP) but not various phosphomonoesters preserve LIF activity in the presence of the serine esterase inhibitor phenylmethylsulfonyl fluoride (PMSF). In this paper I demonstrate that guanosine 3'5'-cyclic monophosphoric acid (3',5'-cGMP), a naturally occurring phosphodiester, at concentrations in excess of 10(-5)M also protects LIF against PMSF inactivation. The effect seems specific for the diester bond, its position in the nucleotide, and the guanine base. The possibility that LIF may be a multifunctional or an allosteric enzyme regulated by 3',5'-cGMP is discussed.", "contents": "Human leukocyte migration inhibitory factor (LIF). IV. 3',5'-cGMP protects LIF against inactivation by the esterase inhibitor phenylmethylsulfonyl fluoride. Recently reported experiments suggest that human leukocyte migration inhibitory factor (LIF) has properties of an esterase and a protease with substrate specificities directed against arginine esters and amides. Also reported previously, the synthetic phosphodiester bis-p-nitrophenyl phosphate (BNPP) but not various phosphomonoesters preserve LIF activity in the presence of the serine esterase inhibitor phenylmethylsulfonyl fluoride (PMSF). In this paper I demonstrate that guanosine 3'5'-cyclic monophosphoric acid (3',5'-cGMP), a naturally occurring phosphodiester, at concentrations in excess of 10(-5)M also protects LIF against PMSF inactivation. The effect seems specific for the diester bond, its position in the nucleotide, and the guanine base. The possibility that LIF may be a multifunctional or an allosteric enzyme regulated by 3',5'-cGMP is discussed."}
{"id": "PMID:204001", "title": "[Bronchopulmonary hamartomas, chondromas, fibromas and myxomas].", "content": "The observation of 23 bronchopulmonary hamartomas, 9 chondromas, one fibroma and one myxoma has provided insight into the particularities of these tumors. The group of hamartomas, tumors of \"erroneous mixture of tissue\", included 20 cases which can be considered a malformation of the entodermal bronchial anlage, and 3 cases which can be regarded as a malformation of the mesenchymal anlage. The first type consists of multiple cleft-like spaces surrounded by ciliated and cuboidal epithelium. There are no alveolar cells. Cartilaginous, fibrous, myxomatous and lipomatous tissue and lymphocytes are also found. The second type consists mainly of undifferentiated mesenchymal cells with tubules, lined by cuboidal epithelial cells or an intestinal type of mucus-secreting epithelium. There may be some immature alveoli, but no ciliated epithelium is found. In contrast to the hamartomas, the chondromas are not derived from a dysontogenetic malformation of the bronchopulmonary tissue but are tumors which develop directly from the bronchial cartilage and are for this reason mainly localized in the endobronchial region. A special form seen in one case is association of pulmonary chondromas, gastric leiomyomas or leiosarcomas and extra-adrenal paraganglioma, though the latter is not always present.", "contents": "[Bronchopulmonary hamartomas, chondromas, fibromas and myxomas]. The observation of 23 bronchopulmonary hamartomas, 9 chondromas, one fibroma and one myxoma has provided insight into the particularities of these tumors. The group of hamartomas, tumors of \"erroneous mixture of tissue\", included 20 cases which can be considered a malformation of the entodermal bronchial anlage, and 3 cases which can be regarded as a malformation of the mesenchymal anlage. The first type consists of multiple cleft-like spaces surrounded by ciliated and cuboidal epithelium. There are no alveolar cells. Cartilaginous, fibrous, myxomatous and lipomatous tissue and lymphocytes are also found. The second type consists mainly of undifferentiated mesenchymal cells with tubules, lined by cuboidal epithelial cells or an intestinal type of mucus-secreting epithelium. There may be some immature alveoli, but no ciliated epithelium is found. In contrast to the hamartomas, the chondromas are not derived from a dysontogenetic malformation of the bronchopulmonary tissue but are tumors which develop directly from the bronchial cartilage and are for this reason mainly localized in the endobronchial region. A special form seen in one case is association of pulmonary chondromas, gastric leiomyomas or leiosarcomas and extra-adrenal paraganglioma, though the latter is not always present."}
{"id": "PMID:204004", "title": "Fasting decreases triiodothyronine receptor capacity.", "content": "Fasting decreases the ratio of hepatic nuclear to serum triiodothyronine (T3) by diminishing the binding capacity of nuclear T3 receptors. In combination with the lower serum T3 concentration caused by fasting, the decrease in receptor content results in a marked decrease in nuclear T3-receptor complexes. The changes in T3 receptor content and circulating T3 in fasted animals appear to be independent synergistic adaptations for caloric conservation in the fasted state. Unlike changes in hormonal level, the modification of nuclear receptor content provides a mechanism that may protect cells with a low caloric reserve independently of the metabolic status of the whole animal.", "contents": "Fasting decreases triiodothyronine receptor capacity. Fasting decreases the ratio of hepatic nuclear to serum triiodothyronine (T3) by diminishing the binding capacity of nuclear T3 receptors. In combination with the lower serum T3 concentration caused by fasting, the decrease in receptor content results in a marked decrease in nuclear T3-receptor complexes. The changes in T3 receptor content and circulating T3 in fasted animals appear to be independent synergistic adaptations for caloric conservation in the fasted state. Unlike changes in hormonal level, the modification of nuclear receptor content provides a mechanism that may protect cells with a low caloric reserve independently of the metabolic status of the whole animal."}
{"id": "PMID:204005", "title": "Lymphocyte function of Michigan dairy farmers exposed to polybrominated biphenyls.", "content": "Michigan dairy farm residents ate farm products containing polybrominated biphenyls (PBB's) after the accidential contamination of animal feed with the chemical in that state in 1973. The circulating blood lymphocytes of these residents show significant changes. Abnormalities include decreases in the numbers and percentages of peripheral blood lymphocytes that form rosettes with either sheep erythrocytes alone or with sheep erythrocytes sensitized with antibody and complement, increases in lymphocytes with no detectable surface markers (\"null\" cells), and altered responses to tests designed to evaluate functional integrity of the cells. There appears to be no consistent correlation between the concentration of PBB's in the plasma and the altered lymphocytes. Studies showed that in Wisconsin dairy farm residents and healthy individuals in the New York area who were not exposed to PBB's there were no such abnormalities.", "contents": "Lymphocyte function of Michigan dairy farmers exposed to polybrominated biphenyls. Michigan dairy farm residents ate farm products containing polybrominated biphenyls (PBB's) after the accidential contamination of animal feed with the chemical in that state in 1973. The circulating blood lymphocytes of these residents show significant changes. Abnormalities include decreases in the numbers and percentages of peripheral blood lymphocytes that form rosettes with either sheep erythrocytes alone or with sheep erythrocytes sensitized with antibody and complement, increases in lymphocytes with no detectable surface markers (\"null\" cells), and altered responses to tests designed to evaluate functional integrity of the cells. There appears to be no consistent correlation between the concentration of PBB's in the plasma and the altered lymphocytes. Studies showed that in Wisconsin dairy farm residents and healthy individuals in the New York area who were not exposed to PBB's there were no such abnormalities."}
{"id": "PMID:204006", "title": "Conformation of [Leu5]enkephalin from X-ray diffraction: features important for recognition at opiate receptor.", "content": "The conformation of [Leu5]enkephalin is produced by a Tyr-Gly-Gly-Phe beta bend stabilized by antiparallel hydrogen bonding between tyrosine and phenylalanine. On the basis of a comparison of the observed structure with the structure of known opiate agonists, three hydrophilic and two hydrophobic regions have been identified as contributing to the recognition of the molecule at the opiate receptor site.", "contents": "Conformation of [Leu5]enkephalin from X-ray diffraction: features important for recognition at opiate receptor. The conformation of [Leu5]enkephalin is produced by a Tyr-Gly-Gly-Phe beta bend stabilized by antiparallel hydrogen bonding between tyrosine and phenylalanine. On the basis of a comparison of the observed structure with the structure of known opiate agonists, three hydrophilic and two hydrophobic regions have been identified as contributing to the recognition of the molecule at the opiate receptor site."}
{"id": "PMID:204007", "title": "Motor nerve sprouting and acetylcholine receptors.", "content": "Sprouting of motor nerve terminals was evoked by functional denervation of skeletal muscles brought about by presynaptic blockade or disuse. The amount of sprouting, determined by morphometric measurement, was correlated with the level of extrajunctional acetylcholine receptors. Sprouting was inhibited by blockade of acetylcholine receptors with alpha-bungarotoxin. Extrajunctional acetylcholine receptors may play an important role in eliciting motor nerve terminal sprouting.", "contents": "Motor nerve sprouting and acetylcholine receptors. Sprouting of motor nerve terminals was evoked by functional denervation of skeletal muscles brought about by presynaptic blockade or disuse. The amount of sprouting, determined by morphometric measurement, was correlated with the level of extrajunctional acetylcholine receptors. Sprouting was inhibited by blockade of acetylcholine receptors with alpha-bungarotoxin. Extrajunctional acetylcholine receptors may play an important role in eliciting motor nerve terminal sprouting."}
{"id": "PMID:204008", "title": "Opiate receptors for behavioral analgesia resemble those related to the depression of spinal nociceptive neurons.", "content": "With naloxone as antagonist, a dose-ratio analysis of the depression by morphine of nociceptive neurons in the spinal cord reveals that this opiate depression of single unit activity has the same pharmacological properties as observed with morphine analgesia. This suggests that the opiate receptor, mediating the observed cellular depression, and those mediating analgesia are presumably the same.", "contents": "Opiate receptors for behavioral analgesia resemble those related to the depression of spinal nociceptive neurons. With naloxone as antagonist, a dose-ratio analysis of the depression by morphine of nociceptive neurons in the spinal cord reveals that this opiate depression of single unit activity has the same pharmacological properties as observed with morphine analgesia. This suggests that the opiate receptor, mediating the observed cellular depression, and those mediating analgesia are presumably the same."}
{"id": "PMID:204010", "title": "Immunity to antigens associated with primate C-type oncoviruses in pregnant women.", "content": "Cell-mediated and humoral immune responses against antigens associated with primate C-type oncoviruses were evaluated in humans by microcytotoxicity and radioimmunoprecipitation assays. Five of six women tested sequentially during pregnancy developed selective cell-mediated reactivity against baboon endogenous virus (BEV)--infected human fibroblasts. Responsiveness peaked during the second and third trimesters and corresponded temporally with elevated antibody levels to BEV antigens. Similar cell-mediated reactivity was not observed in nonpregnant individuals. Selective cell-mediated reactivity directed against cells infected with the simian sarcoma virus-simian sarcoma associated virus complex (SSV--SSAV) was observed in four of 20 healthy adults (three of 14 nonpregnant, one of six pregnant). These observations suggest that cell-mediated reactivity against primate C-type oncoviruses is occasionally detected in healthy nonpregnant adults, but that during pregnancy both cell-mediated and humoral reactivity against BEV may become selectively expressed.", "contents": "Immunity to antigens associated with primate C-type oncoviruses in pregnant women. Cell-mediated and humoral immune responses against antigens associated with primate C-type oncoviruses were evaluated in humans by microcytotoxicity and radioimmunoprecipitation assays. Five of six women tested sequentially during pregnancy developed selective cell-mediated reactivity against baboon endogenous virus (BEV)--infected human fibroblasts. Responsiveness peaked during the second and third trimesters and corresponded temporally with elevated antibody levels to BEV antigens. Similar cell-mediated reactivity was not observed in nonpregnant individuals. Selective cell-mediated reactivity directed against cells infected with the simian sarcoma virus-simian sarcoma associated virus complex (SSV--SSAV) was observed in four of 20 healthy adults (three of 14 nonpregnant, one of six pregnant). These observations suggest that cell-mediated reactivity against primate C-type oncoviruses is occasionally detected in healthy nonpregnant adults, but that during pregnancy both cell-mediated and humoral reactivity against BEV may become selectively expressed."}
{"id": "PMID:204011", "title": "Inhibition of bone resorption in vitro by a cartilage-derived anticollagenase factor.", "content": "A cartilage-derived factor containing a specific collagenous inhibitor was found to block reversibly parathyroid hormone-stimulated 45Ca release from fetal rat bone in vitro. Morphologic and quantitative histometric examination revealed that this factor modulates osteoclastic activities.", "contents": "Inhibition of bone resorption in vitro by a cartilage-derived anticollagenase factor. A cartilage-derived factor containing a specific collagenous inhibitor was found to block reversibly parathyroid hormone-stimulated 45Ca release from fetal rat bone in vitro. Morphologic and quantitative histometric examination revealed that this factor modulates osteoclastic activities."}
{"id": "PMID:204012", "title": "Dual actions of substance P on nociception: possible role of endogenous opioids.", "content": "Substance P produces analgesia when administered to mice in very small doses by the intraventricular route (1.25 to 5 nanograms per mouse). The analgesic effect can be blocked by naloxone. At higher doses (greater than 50 nanograms per mouse), this activity is lost. At these higher doses, however, substance P produced hyperalgesia when combined with naloxone and analgesia when combined with baclofen [beta-(4-chlorophenyl)-gamma-aminobutyric acid]. Substance P may have dual actions in brain, releasing endorphins at very low doses and directly exciting neuronal activity in nociceptive pathways at higher doses.", "contents": "Dual actions of substance P on nociception: possible role of endogenous opioids. Substance P produces analgesia when administered to mice in very small doses by the intraventricular route (1.25 to 5 nanograms per mouse). The analgesic effect can be blocked by naloxone. At higher doses (greater than 50 nanograms per mouse), this activity is lost. At these higher doses, however, substance P produced hyperalgesia when combined with naloxone and analgesia when combined with baclofen [beta-(4-chlorophenyl)-gamma-aminobutyric acid]. Substance P may have dual actions in brain, releasing endorphins at very low doses and directly exciting neuronal activity in nociceptive pathways at higher doses."}
{"id": "PMID:204013", "title": "Production of antibody to tetanus toxoid by continuous human lymphoblastoid cell lines.", "content": "Peripheral lymphocytes from human volunteers boosted with tetanus toxoid were cultured after in vitro infection with Epstein-Barr virus. Forty-four continuous lymphoblastoid lines were established which continued to secrete human gamma globulin; seven of these secreted antibody to tetanus toxoid. Subcultures derived from limiting dilution experiments continued to secrete the antibody. Some of these antibody-secreting cells have been in continuous culture for more than 6 months.", "contents": "Production of antibody to tetanus toxoid by continuous human lymphoblastoid cell lines. Peripheral lymphocytes from human volunteers boosted with tetanus toxoid were cultured after in vitro infection with Epstein-Barr virus. Forty-four continuous lymphoblastoid lines were established which continued to secrete human gamma globulin; seven of these secreted antibody to tetanus toxoid. Subcultures derived from limiting dilution experiments continued to secrete the antibody. Some of these antibody-secreting cells have been in continuous culture for more than 6 months."}
{"id": "PMID:204014", "title": "Genetic mapping of xenotropic leukemia virus-inducing loci in two mouse strains.", "content": "In genetic studies of C57BL/10 and BALB/c mice, inducibility of xenotropic murine leukemia virus from tissue cultures by treatment with 5-iododeoxyuridine shows single gene segregation ratios. In both strains, the virus-inducing loci are on chromosome 1, linked to the Dip-1/isozyme locus, but the two may not be at allelic sites.", "contents": "Genetic mapping of xenotropic leukemia virus-inducing loci in two mouse strains. In genetic studies of C57BL/10 and BALB/c mice, inducibility of xenotropic murine leukemia virus from tissue cultures by treatment with 5-iododeoxyuridine shows single gene segregation ratios. In both strains, the virus-inducing loci are on chromosome 1, linked to the Dip-1/isozyme locus, but the two may not be at allelic sites."}
{"id": "PMID:204015", "title": "Specific-opiate-induced depression of transmitter release from dorsal root ganglion cells in culture.", "content": "The opiate etorphine depresses monosynaptic excitatory postsynaptic potentials (EPSP's) elicited in spinal cord cells by activation of dorsal root ganglion cells in murine neuronal cell culture. The depression is reversed by naloxone. Statistical analysis of the synaptic responses reveals that the opiate reduces EPSP quantal content at this synapse without altering quantal size. Therefore, the opiate action is presynaptic and affects transmitter release rather than postsynaptic responsiveness.", "contents": "Specific-opiate-induced depression of transmitter release from dorsal root ganglion cells in culture. The opiate etorphine depresses monosynaptic excitatory postsynaptic potentials (EPSP's) elicited in spinal cord cells by activation of dorsal root ganglion cells in murine neuronal cell culture. The depression is reversed by naloxone. Statistical analysis of the synaptic responses reveals that the opiate reduces EPSP quantal content at this synapse without altering quantal size. Therefore, the opiate action is presynaptic and affects transmitter release rather than postsynaptic responsiveness."}
{"id": "PMID:204016", "title": "Opiate peptide modulation of amino acid responses suggests novel form of neuronal communication.", "content": "Mouse spinal neurons grown in tissue culture were used to study the electrophysiological pharmacology of the opiate peptide leucine-enkephalin. Enkephalin depressed glutamate-evoked responses in a noncompetitive manner independent of any other effects on membrane properties. The results demonstrate a neuromodulatory action of opiate peptide functionally distinct from the conventional neurotransmitter class of operation.", "contents": "Opiate peptide modulation of amino acid responses suggests novel form of neuronal communication. Mouse spinal neurons grown in tissue culture were used to study the electrophysiological pharmacology of the opiate peptide leucine-enkephalin. Enkephalin depressed glutamate-evoked responses in a noncompetitive manner independent of any other effects on membrane properties. The results demonstrate a neuromodulatory action of opiate peptide functionally distinct from the conventional neurotransmitter class of operation."}
{"id": "PMID:204017", "title": "[Scanning electron microscopy study of the synovial membrane in rheumatoid arthritis].", "content": "A comparative study under the scanning electron microscope of rheumatoid synovial membranes, 5 arthrosic synovial membranes, one tuberculous membrane, and 3 normal synovial membranes showed the pathological changes in the synovial membrane due to rheumatoid arthritis: Inflammatory aspect of the synovial fringes, surrounded by turgid and proliferative villous processes. Granular appearance of the endo-articular surface like a \"pebble beach\". Dome-shaped synoviocyte layer, standing out well above the subjacent intimal layer, associated with small round cells, also with a raised margin, covering most of the endo-articular surface. Plasma membrane of the superficial synovial cells, covered with numerous and various differentiations and abundant microvillous processes. Reticular deposits or layers, covering the apical poles of the synoviocytes.", "contents": "[Scanning electron microscopy study of the synovial membrane in rheumatoid arthritis]. A comparative study under the scanning electron microscope of rheumatoid synovial membranes, 5 arthrosic synovial membranes, one tuberculous membrane, and 3 normal synovial membranes showed the pathological changes in the synovial membrane due to rheumatoid arthritis: Inflammatory aspect of the synovial fringes, surrounded by turgid and proliferative villous processes. Granular appearance of the endo-articular surface like a \"pebble beach\". Dome-shaped synoviocyte layer, standing out well above the subjacent intimal layer, associated with small round cells, also with a raised margin, covering most of the endo-articular surface. Plasma membrane of the superficial synovial cells, covered with numerous and various differentiations and abundant microvillous processes. Reticular deposits or layers, covering the apical poles of the synoviocytes."}
{"id": "PMID:204018", "title": "[Interpretation of and indications for bone scintiscans].", "content": "The interpretatiton of a bone radioisotope scan requires perfect knowledge of normal skeletal appearances, shadows outside the bones and the various methods of expression of bony lesions: generally hyperfixations but sometimes isofixations or even hypofixations. A bone scan permits one to make an overall assessment of multiple bony lesions, determine the extent of a lesion, detect bony complications of a disease or treatment and seek the bony origin of a pain.", "contents": "[Interpretation of and indications for bone scintiscans]. The interpretatiton of a bone radioisotope scan requires perfect knowledge of normal skeletal appearances, shadows outside the bones and the various methods of expression of bony lesions: generally hyperfixations but sometimes isofixations or even hypofixations. A bone scan permits one to make an overall assessment of multiple bony lesions, determine the extent of a lesion, detect bony complications of a disease or treatment and seek the bony origin of a pain."}
{"id": "PMID:204019", "title": "[Lumbosacral arachnoepiduritis. Clinical and etiologic aspects].", "content": "A series of 120 cases of lumbo-sacral arachno-epiduritis was studied from the clinical and etiological points of view. The recruitment of the cases and their classification were based on purely radiological criteria. The clinical symptoms were various, non-specific and without correlation with the radiological type. The course was chronic with a change in the distribution of the symptoms. The influence of the method of examination was discussed in the 9 cases discussed after a first myelography without surgical operation. All the forms suggesting epidural lesions were post-operative and observed mainly in cases of laminectomy.", "contents": "[Lumbosacral arachnoepiduritis. Clinical and etiologic aspects]. A series of 120 cases of lumbo-sacral arachno-epiduritis was studied from the clinical and etiological points of view. The recruitment of the cases and their classification were based on purely radiological criteria. The clinical symptoms were various, non-specific and without correlation with the radiological type. The course was chronic with a change in the distribution of the symptoms. The influence of the method of examination was discussed in the 9 cases discussed after a first myelography without surgical operation. All the forms suggesting epidural lesions were post-operative and observed mainly in cases of laminectomy."}
{"id": "PMID:204020", "title": "[Gamma heavy chain disease associated with rheumatoid arthritis. Spontaneous disappearance of the pathologic protein].", "content": "The authors report the chance discovery in a man aged 53 years with serum positive rheumatoid arthritis, of gamma 3 heavy chain disease. The originality of this case depended on the absence of any detectable lymphoid proliferation and on the transient character of the pathological protein. Only the course after a long follow up will determine whether there is no incipient lymphoid proliferation and whether the heavy chain disease has disappeared permanently.", "contents": "[Gamma heavy chain disease associated with rheumatoid arthritis. Spontaneous disappearance of the pathologic protein]. The authors report the chance discovery in a man aged 53 years with serum positive rheumatoid arthritis, of gamma 3 heavy chain disease. The originality of this case depended on the absence of any detectable lymphoid proliferation and on the transient character of the pathological protein. Only the course after a long follow up will determine whether there is no incipient lymphoid proliferation and whether the heavy chain disease has disappeared permanently."}
{"id": "PMID:204021", "title": "[Interactions of salicylates and other nonsteroid anti-inflammatory agents].", "content": "The salicylates are frequently associated in every day treatment with other non-steroid anti-inflammatory drugs, which justifies a study of their interactions. Animal pharmacodynamics, although interesting, is of little practical interest. Pharmacokinetic research seems to indicate that aspirin reduces the bio-availability of other non steroid anti-inflammatory drugs, which has not yet been confirmed clinically. It is still premature to conclude, but the already established facts suggest the continuation of such studies.", "contents": "[Interactions of salicylates and other nonsteroid anti-inflammatory agents]. The salicylates are frequently associated in every day treatment with other non-steroid anti-inflammatory drugs, which justifies a study of their interactions. Animal pharmacodynamics, although interesting, is of little practical interest. Pharmacokinetic research seems to indicate that aspirin reduces the bio-availability of other non steroid anti-inflammatory drugs, which has not yet been confirmed clinically. It is still premature to conclude, but the already established facts suggest the continuation of such studies."}
{"id": "PMID:204022", "title": "[Male pseudohermaphroditism. Etiologic diagnosis. 2].", "content": "The cause of male pseudohermaphroditism : polydystrophy, gonadal dysplasia, agenesis or precocious abiotrophy of Leydig cells, defect of testicular stimulation by foetal hypophysis, testosterone, biosynthesis abnormalities 5 varieties of which are identified, 5 alpha reductase defect, testosterone or dihydrotestosterone insenstivity complete and incomplete forms, defect of secretion or action of Mullerian ducts inhibitor can be found in the majority of cases by clinical and para-clinical analysis. Practical management results from this diagnosis.", "contents": "[Male pseudohermaphroditism. Etiologic diagnosis. 2]. The cause of male pseudohermaphroditism : polydystrophy, gonadal dysplasia, agenesis or precocious abiotrophy of Leydig cells, defect of testicular stimulation by foetal hypophysis, testosterone, biosynthesis abnormalities 5 varieties of which are identified, 5 alpha reductase defect, testosterone or dihydrotestosterone insenstivity complete and incomplete forms, defect of secretion or action of Mullerian ducts inhibitor can be found in the majority of cases by clinical and para-clinical analysis. Practical management results from this diagnosis."}
{"id": "PMID:204023", "title": "[Fetomaternal rhesus immunization in Algeria].", "content": "The frequency and modalities of immunisation in the rhesus system were studied in 847 rhesus negative. Algerian women, and in 247 foreign women. 33% of the Algerian women and 8% of the foreign women were immunised. The high muliparity still frequent in Algeria is one of the causes of this difference. The specificity of the antibodies, the mode of foetal involvement, and the antibody titre in relation to the number of pregnancies and the month of the pregnancy are indicated.", "contents": "[Fetomaternal rhesus immunization in Algeria]. The frequency and modalities of immunisation in the rhesus system were studied in 847 rhesus negative. Algerian women, and in 247 foreign women. 33% of the Algerian women and 8% of the foreign women were immunised. The high muliparity still frequent in Algeria is one of the causes of this difference. The specificity of the antibodies, the mode of foetal involvement, and the antibody titre in relation to the number of pregnancies and the month of the pregnancy are indicated."}
{"id": "PMID:204029", "title": "[Division of the pituitary stalk (mischotomy) for malignant exophthalmos after treatment of Basedow's disease with I 131].", "content": "The authors report a case of malignant exophthalmia occuring after treatment of Grave's disease with I 131. The exophthalmia was resistant to corticosteroids, thyroxin in large doses, reserpine, and the patient was treated by mischotomy (division of the pituitary stalk with interposition of polyethylene strips). There was progressive marked regression of the exophthalmia with return to work and normal social life.", "contents": "[Division of the pituitary stalk (mischotomy) for malignant exophthalmos after treatment of Basedow's disease with I 131]. The authors report a case of malignant exophthalmia occuring after treatment of Grave's disease with I 131. The exophthalmia was resistant to corticosteroids, thyroxin in large doses, reserpine, and the patient was treated by mischotomy (division of the pituitary stalk with interposition of polyethylene strips). There was progressive marked regression of the exophthalmia with return to work and normal social life."}
{"id": "PMID:204030", "title": "[Splenic lesions during benign inoculation lymphoreticulosis].", "content": "The authors describe the fibro-granulomatous lesions with scar formation on a splenectomy specimen removed for familial spherocytosis, eight weeks after the onset of cat scratch disease. This original observation, apparently unique in the literature, is in favour of the blood spread of the agent responsible for benign inoculation lymphoreticulosis, and suggests a pathogenic theory for the unusual visceral manifestations.", "contents": "[Splenic lesions during benign inoculation lymphoreticulosis]. The authors describe the fibro-granulomatous lesions with scar formation on a splenectomy specimen removed for familial spherocytosis, eight weeks after the onset of cat scratch disease. This original observation, apparently unique in the literature, is in favour of the blood spread of the agent responsible for benign inoculation lymphoreticulosis, and suggests a pathogenic theory for the unusual visceral manifestations."}
{"id": "PMID:204031", "title": "[Volvulus of the ascending colon. Apropos of 5 cases].", "content": "The authors report five cases of volvulus of the right side of the colon, including 3 with complications, which required segmental colonic resection. They recall the diagnostic and therapeutic problems, emphasising the interest of barium enema, the necessity of early diagnosis, the high level of mortality and the treatment of choice which is right hemicolectomy.", "contents": "[Volvulus of the ascending colon. Apropos of 5 cases]. The authors report five cases of volvulus of the right side of the colon, including 3 with complications, which required segmental colonic resection. They recall the diagnostic and therapeutic problems, emphasising the interest of barium enema, the necessity of early diagnosis, the high level of mortality and the treatment of choice which is right hemicolectomy."}
{"id": "PMID:204039", "title": "[Shunt between Disse spaces and biliary canaliculi and its pathology].", "content": "The existence and permeability of communications between Disse spaces and biliary canaliculi has been finally accepted, in spite of the socalled obstacle of the water-tight junctions. The explanation of pigmented bile secretion by filtration and reabsorption has become plausible. Whilst other subtances excreted by the bile after having been filtered at the level of the sinusoidal wall need to enter the hepatic cell to be synthesised, stocked or to take up their final shape, the bile pigments, cell debris, cross the hepatic lobule through the shunt between the Disse space and the bile canaliculi, without passing through the liver cell. These facts require us today to reconsider the physiopathology of some liver disorders, especially those accompanied by jaundice.", "contents": "[Shunt between Disse spaces and biliary canaliculi and its pathology]. The existence and permeability of communications between Disse spaces and biliary canaliculi has been finally accepted, in spite of the socalled obstacle of the water-tight junctions. The explanation of pigmented bile secretion by filtration and reabsorption has become plausible. Whilst other subtances excreted by the bile after having been filtered at the level of the sinusoidal wall need to enter the hepatic cell to be synthesised, stocked or to take up their final shape, the bile pigments, cell debris, cross the hepatic lobule through the shunt between the Disse space and the bile canaliculi, without passing through the liver cell. These facts require us today to reconsider the physiopathology of some liver disorders, especially those accompanied by jaundice."}
{"id": "PMID:204040", "title": "[Intestinal hemorrhage due to blind loops. 3 cases and review of the literature].", "content": "The authors report 3 cases of intestinal bleeding either micro- or macroscopic induced by ulcers in blind loops. The blind loops developed in all 3 cases on side-to-side ileocolic anastomoses. In one of the patients, the ulcers were demonstrated by colonoscopy. The 3 cases reported are quite comparable to the 18 cases found in the world literature. These hemorrhages may become severe by their abundance or repetition, but a cure is easily obtained by resection of the intestinal blind loops and restoration of the continuity by end-to-end anastomosis.", "contents": "[Intestinal hemorrhage due to blind loops. 3 cases and review of the literature]. The authors report 3 cases of intestinal bleeding either micro- or macroscopic induced by ulcers in blind loops. The blind loops developed in all 3 cases on side-to-side ileocolic anastomoses. In one of the patients, the ulcers were demonstrated by colonoscopy. The 3 cases reported are quite comparable to the 18 cases found in the world literature. These hemorrhages may become severe by their abundance or repetition, but a cure is easily obtained by resection of the intestinal blind loops and restoration of the continuity by end-to-end anastomosis."}
{"id": "PMID:204041", "title": "[Idiopathic thrombopenic purpura in Algeria].", "content": "The study in Algeria over a period of 3 years of 90 cases of idiopathic thrombopenic purpura out of 409 hemorrhagic syndromes, showed the following peculiarities: the chronic forms are as frequent in the child as in the adult and we did not observe any subacute forms. Except in one case the use of prednisone at a dose of 2 mg/kg gave no result in patients who were not improved by a dose of 1 mg/kg.", "contents": "[Idiopathic thrombopenic purpura in Algeria]. The study in Algeria over a period of 3 years of 90 cases of idiopathic thrombopenic purpura out of 409 hemorrhagic syndromes, showed the following peculiarities: the chronic forms are as frequent in the child as in the adult and we did not observe any subacute forms. Except in one case the use of prednisone at a dose of 2 mg/kg gave no result in patients who were not improved by a dose of 1 mg/kg."}
{"id": "PMID:204042", "title": "[Ebstein's disease. Study of 5 personal cases].", "content": "Ebstein's disease is a frequently cyanotic form of congenital heart disease. The lesions consist of low implantation in the right ventricle of the tricuspid valves, often associated with an atrial septal defect. Our five cases (two men and 3 women) had a variable clinical presentation depending on the degree of the variable clinical presentation depending on the degree of the lesions. A fairly exceptional fact should be emphasised, which is that 3 of our patients brought to term or almost to term 3 pregnancies and gave birth to live children. Ebstein's disease should be suspected when a large heart with a rugby football shape is discovered on X ray and E.C.G., together with right atrial hypertrophy, frequent elongation of the P-R interval, low voltage and complete right bundle branch block. The diagnosis can be confirmed by angiocardiography and catheterisation. Angiocardiography shows a large right atrium and a distal right ventricle in the form of a small chamber with thin walls. Catheterisation is essential and detects the atrial septal defect in 80% of cases and a pressure gradiant intermediate between atrial and ventricular pressures, revealing ventricular morphology. Surgical treatment will be either palliative (cavo-pulmonary anastomosis) or curative: Hunter's operation (Lillehei-Hardy) implantation of the tricuspid on the atrio-ventricular ring. The prognosis is then worse.", "contents": "[Ebstein's disease. Study of 5 personal cases]. Ebstein's disease is a frequently cyanotic form of congenital heart disease. The lesions consist of low implantation in the right ventricle of the tricuspid valves, often associated with an atrial septal defect. Our five cases (two men and 3 women) had a variable clinical presentation depending on the degree of the variable clinical presentation depending on the degree of the lesions. A fairly exceptional fact should be emphasised, which is that 3 of our patients brought to term or almost to term 3 pregnancies and gave birth to live children. Ebstein's disease should be suspected when a large heart with a rugby football shape is discovered on X ray and E.C.G., together with right atrial hypertrophy, frequent elongation of the P-R interval, low voltage and complete right bundle branch block. The diagnosis can be confirmed by angiocardiography and catheterisation. Angiocardiography shows a large right atrium and a distal right ventricle in the form of a small chamber with thin walls. Catheterisation is essential and detects the atrial septal defect in 80% of cases and a pressure gradiant intermediate between atrial and ventricular pressures, revealing ventricular morphology. Surgical treatment will be either palliative (cavo-pulmonary anastomosis) or curative: Hunter's operation (Lillehei-Hardy) implantation of the tricuspid on the atrio-ventricular ring. The prognosis is then worse."}
{"id": "PMID:204047", "title": "[Mortality due to tuberculosis. Statistical concepts].", "content": "The mortality statistics due to tuberculosis drawn up by INSERM for the years 1968-1973 show the rate to be 0.86% in the Paris region. A study based on autopsy results of 7,400 adults gave a rate of 3.3%. The causes of this discrepancy are analysed.", "contents": "[Mortality due to tuberculosis. Statistical concepts]. The mortality statistics due to tuberculosis drawn up by INSERM for the years 1968-1973 show the rate to be 0.86% in the Paris region. A study based on autopsy results of 7,400 adults gave a rate of 3.3%. The causes of this discrepancy are analysed."}
{"id": "PMID:204048", "title": "[Fulminating refractory hypoxemia. Apropos of 3 cases including 1 case of tuberculosis].", "content": "The authors report 3 cases of refractory fulminant hypoxemia. The etiology was various, neoplastic lymphangitis, influenza and tuberculosis. The authors emphasize the role of tuberculosis in the onset of certain diffuse interstitial fibroses.", "contents": "[Fulminating refractory hypoxemia. Apropos of 3 cases including 1 case of tuberculosis]. The authors report 3 cases of refractory fulminant hypoxemia. The etiology was various, neoplastic lymphangitis, influenza and tuberculosis. The authors emphasize the role of tuberculosis in the onset of certain diffuse interstitial fibroses."}
{"id": "PMID:204049", "title": "[Diaphyseal bone tuberculosis].", "content": "The authors report a case of diaphyseal bony tuberculosis, in which the diagnosis was not made for a long time as bony tuberculosis is considered exceptional and owing to the presence of a staphylococcus which oriented the diagnosis towards osteomyelitis. Bony tuberculosis certainly affects more easily immigrant patients, in whom one may see multifocal forms, but also affects those who, by their environment, might imagine they are protected, and it is not exceptional to see unifocal forms.", "contents": "[Diaphyseal bone tuberculosis]. The authors report a case of diaphyseal bony tuberculosis, in which the diagnosis was not made for a long time as bony tuberculosis is considered exceptional and owing to the presence of a staphylococcus which oriented the diagnosis towards osteomyelitis. Bony tuberculosis certainly affects more easily immigrant patients, in whom one may see multifocal forms, but also affects those who, by their environment, might imagine they are protected, and it is not exceptional to see unifocal forms."}
{"id": "PMID:204051", "title": "[Multi-focal tuberculosis].", "content": "The authors present 16 cases of multifocal tuberculosis observed over a period of five years on a general medical unit. These cases almost all occurred in immigrants. (14 out of 16) with at least 2 localisations in 9 of them and sometimes 3 or more. The viscera usually affected were, in order, the liver, the lymph nodes, the lungs and pleura, the joints. They emphasise the mildness of the clinical symptoms, the rareness of lung involvement and, on the contrary, the constancy of hepatic involvement so that needle biopsy of the liver is essential in diagnosis.", "contents": "[Multi-focal tuberculosis]. The authors present 16 cases of multifocal tuberculosis observed over a period of five years on a general medical unit. These cases almost all occurred in immigrants. (14 out of 16) with at least 2 localisations in 9 of them and sometimes 3 or more. The viscera usually affected were, in order, the liver, the lymph nodes, the lungs and pleura, the joints. They emphasise the mildness of the clinical symptoms, the rareness of lung involvement and, on the contrary, the constancy of hepatic involvement so that needle biopsy of the liver is essential in diagnosis."}
{"id": "PMID:204052", "title": "[Tuberculosis and caustic eso-gastric burns. Critical reflections on one case].", "content": "The diagnostic problems which may be raised during caustic oesophago-gastric burns and concommittent tuberculosis, of which the symptoms may be masked by the richness of the initial clinical picture are discussed here. The authors emphasise the necessity of prophylactic anti-tuberculous treatment, before any surgery when there is any suggestion of tuberculosis even siabilised.", "contents": "[Tuberculosis and caustic eso-gastric burns. Critical reflections on one case]. The diagnostic problems which may be raised during caustic oesophago-gastric burns and concommittent tuberculosis, of which the symptoms may be masked by the richness of the initial clinical picture are discussed here. The authors emphasise the necessity of prophylactic anti-tuberculous treatment, before any surgery when there is any suggestion of tuberculosis even siabilised."}
{"id": "PMID:204053", "title": "[Extrinsic allergic alveolitis of drug origin].", "content": "Extrinsic allergic alveolitis of drug origin is now a better known branch of respiratory pathology. The symptoms and course of these cases resemble in many ways those of extrinsic allergic alveolitis in general with a few differences. The list of drugs responsible is longer every day, and it is important to be aware of it. The diagnosis of these diseases is not always easy, as there are certain similarities between them and other long diseases either iatrogenic or not, but not immuno-allergic. Our physiopathological knowledge is based on already known data concerning allergic alveolitis, but includes many theories which still have to be verified. It is important for the clinician to be aware of this new type of respiratory disease as the treatment includes withdrawal of the responsible drug as soon as possible, failing which irreversible pulmonary fibrosis develops.", "contents": "[Extrinsic allergic alveolitis of drug origin]. Extrinsic allergic alveolitis of drug origin is now a better known branch of respiratory pathology. The symptoms and course of these cases resemble in many ways those of extrinsic allergic alveolitis in general with a few differences. The list of drugs responsible is longer every day, and it is important to be aware of it. The diagnosis of these diseases is not always easy, as there are certain similarities between them and other long diseases either iatrogenic or not, but not immuno-allergic. Our physiopathological knowledge is based on already known data concerning allergic alveolitis, but includes many theories which still have to be verified. It is important for the clinician to be aware of this new type of respiratory disease as the treatment includes withdrawal of the responsible drug as soon as possible, failing which irreversible pulmonary fibrosis develops."}
{"id": "PMID:204057", "title": "Atopic dermatitis, eczema herpeticum, infectious mononucleosis, and depressed cell-mediated immunity.", "content": "An immunologic investigation was undertaken in a patient with atopic dermatitis and infectious mononucleosis complicated by eczema herpeticum. Humoral immunity was normal. The cell-mediated immune (CMI) response was temporarily depressed during the acute phase of the illness as measured by in vivo skin tests, and in vitro tests using T-lymphocyte population, macrophage inhibition factor, and lymphocyte transformation. It is postulated that the depression of CMI caused by infectious mononucleosis precipitated the development of eczema herpeticum in this patient.", "contents": "Atopic dermatitis, eczema herpeticum, infectious mononucleosis, and depressed cell-mediated immunity. An immunologic investigation was undertaken in a patient with atopic dermatitis and infectious mononucleosis complicated by eczema herpeticum. Humoral immunity was normal. The cell-mediated immune (CMI) response was temporarily depressed during the acute phase of the illness as measured by in vivo skin tests, and in vitro tests using T-lymphocyte population, macrophage inhibition factor, and lymphocyte transformation. It is postulated that the depression of CMI caused by infectious mononucleosis precipitated the development of eczema herpeticum in this patient."}
{"id": "PMID:204058", "title": "A multicentric, randomized clinical trial of Gaviscon in reflux esophagitis.", "content": "Gaviscon tablets and the standard antacid proved equally effective in reducing the number of heartburn attacks. Chi-square tests revealed no significant difference between the two treatment groups at the end of weeks 1, 2, 3, or 4. Heartburn score was arrived at by multiplying heartburn incidence by heartburn severity. This heartburn score also indicated no significant difference between the two treatment groups at the end of the four weeks. Tabulation of the mean number of tablets consumed by patients in the two groups was made. There was no significant difference between the two groups in tablet consumption, indicating equal demand as well as equal compliance in the two groups. Esophagoscopy done before and after 28 days of treatment showed that Gaviscon and the standard antacid tablets were equally effective in each group. There was significant, and equal, decrease in the severity in the specific signs of esophagitis, friability, erosion, and ulceration in both treatment groups, as well as in such nonspecific signs as hyperemia, edema, and exudate. The validity and clinical acceptance of an alginic acid-containing agent, Gaviscon, which through a foaming action delivers a minimal dose of antacid directly at the site of acid irritation of the esophageal mucosa, has been confirmed in a multicentric, well-controlled randomized clinical trial.", "contents": "A multicentric, randomized clinical trial of Gaviscon in reflux esophagitis. Gaviscon tablets and the standard antacid proved equally effective in reducing the number of heartburn attacks. Chi-square tests revealed no significant difference between the two treatment groups at the end of weeks 1, 2, 3, or 4. Heartburn score was arrived at by multiplying heartburn incidence by heartburn severity. This heartburn score also indicated no significant difference between the two treatment groups at the end of the four weeks. Tabulation of the mean number of tablets consumed by patients in the two groups was made. There was no significant difference between the two groups in tablet consumption, indicating equal demand as well as equal compliance in the two groups. Esophagoscopy done before and after 28 days of treatment showed that Gaviscon and the standard antacid tablets were equally effective in each group. There was significant, and equal, decrease in the severity in the specific signs of esophagitis, friability, erosion, and ulceration in both treatment groups, as well as in such nonspecific signs as hyperemia, edema, and exudate. The validity and clinical acceptance of an alginic acid-containing agent, Gaviscon, which through a foaming action delivers a minimal dose of antacid directly at the site of acid irritation of the esophageal mucosa, has been confirmed in a multicentric, well-controlled randomized clinical trial."}
{"id": "PMID:204061", "title": "Clofibrate-induced complications in renal disease: a case report.", "content": "A young male nephrotic patient, who was given small doses of clofibrate for hyperlipaemia, developed muscle pain, stiffness and very high serum levels of muscle enzymes. The myopathy remitted completely after administration of clofibrate was stopped. He also displayed a transient mononeuropathy and rapid deterioration of previously stable renal function, so that he required maintenance dialysis. Clofibrate has particular dangers in patients with uraemia or hypoproteinaemia, and we recommend that it be used with great caution in patients with renal disease.", "contents": "Clofibrate-induced complications in renal disease: a case report. A young male nephrotic patient, who was given small doses of clofibrate for hyperlipaemia, developed muscle pain, stiffness and very high serum levels of muscle enzymes. The myopathy remitted completely after administration of clofibrate was stopped. He also displayed a transient mononeuropathy and rapid deterioration of previously stable renal function, so that he required maintenance dialysis. Clofibrate has particular dangers in patients with uraemia or hypoproteinaemia, and we recommend that it be used with great caution in patients with renal disease."}
{"id": "PMID:204062", "title": "Malignant cystosarcoma phyllodes associated with scirrhous carcinoma of the breast: a case report.", "content": "The presence of a malignant cystosarcoma phyllodes in one breast and a scirrhous carcinoma in the opposite breast in a premenopausal Black woman is described. Malignant cystosarcoma phyllodes is uncommon and its rare association with carcinoma of the breast is mentioned.", "contents": "Malignant cystosarcoma phyllodes associated with scirrhous carcinoma of the breast: a case report. The presence of a malignant cystosarcoma phyllodes in one breast and a scirrhous carcinoma in the opposite breast in a premenopausal Black woman is described. Malignant cystosarcoma phyllodes is uncommon and its rare association with carcinoma of the breast is mentioned."}
{"id": "PMID:204063", "title": "Hepatoma presenting as a bone tumour: a case report.", "content": "Osseous metastases from hepatoma are rare. One patient who had a lesion in the upper humerus is presented.", "contents": "Hepatoma presenting as a bone tumour: a case report. Osseous metastases from hepatoma are rare. One patient who had a lesion in the upper humerus is presented."}
{"id": "PMID:204064", "title": "Rotavirus and winter gastro-enteritis in White South African infants.", "content": "In a microbiological investigation of winter gastro-enteritis in 23 White children rotaviruses were found in 14 (61%) and parvovirus-like particles in 1 (4%). Bacteriological examination of stools from 11 of these patients yielded one isolate of Salmonella eastbourne, but no enterotoxigenic or invasive bacteria were found. Rotavirus appears to be the main aetiological agent of acute winter gastro-enteritis in White infants.", "contents": "Rotavirus and winter gastro-enteritis in White South African infants. In a microbiological investigation of winter gastro-enteritis in 23 White children rotaviruses were found in 14 (61%) and parvovirus-like particles in 1 (4%). Bacteriological examination of stools from 11 of these patients yielded one isolate of Salmonella eastbourne, but no enterotoxigenic or invasive bacteria were found. Rotavirus appears to be the main aetiological agent of acute winter gastro-enteritis in White infants."}
{"id": "PMID:204066", "title": "Somatic cell hybrids between Friend erythroleukemia cells and mouse hepatoma cells.", "content": "Somatic cell hybrids between hepatoma and Friend erythroleukemia parental cells were studied for the expression of liver-specific and erythroid properties. Several independent clones were isolated using HAT selection and were shown to be true hybrids by isozyme and chromosome analysis. All displayed a complete extinction of hemoglobin and globin mRNA production, but a retention of albumin and transferrin secretion. The data suggest that erythroid differntiation is being actively inhibited by the hepatoma genome. Possible mechanisms that might explain these results are discussed in the light of current hypotheses regarding the mechanism of cell differentiation.", "contents": "Somatic cell hybrids between Friend erythroleukemia cells and mouse hepatoma cells. Somatic cell hybrids between hepatoma and Friend erythroleukemia parental cells were studied for the expression of liver-specific and erythroid properties. Several independent clones were isolated using HAT selection and were shown to be true hybrids by isozyme and chromosome analysis. All displayed a complete extinction of hemoglobin and globin mRNA production, but a retention of albumin and transferrin secretion. The data suggest that erythroid differntiation is being actively inhibited by the hepatoma genome. Possible mechanisms that might explain these results are discussed in the light of current hypotheses regarding the mechanism of cell differentiation."}
{"id": "PMID:204067", "title": "Transfer of the human genes coding for thymidine kinase and galactokinase to Chinese hamster cells and human-Chinese hamster cell hybrids.", "content": "Cotransfer of two linked human genes, coding for the enzymes thymidine kinase (TK) and galactokinase (Gak) was demonstrated following incubation of Chinese hamster TK-deficient cells with isolated human chromosomes. The 5 colonies which were isolated all expressed a stable TK-positive phenotype. Cotransfer of the human genes coding for TK and Gak has also been observed in experiments in which isolated human chromosomes were incubated with TK-deficient human-Chinese hamster cell hybrids. These receipient hybrids had lost all human chromosomes at the time of incubation. From these experiments, four colonies were isolated, all expressing an unstable TK-positive phenotype. Using chromosome staining techniques, the presence of human chromosomes could not be demonstrated in either of the transformed clonal lines obtained with the Chinese hamster and the hybrid recipient cells. This indicates that incorporation of only the fragment of the human chromosome 17, bearing the genes for TK and Gak, has occurred in the recipient cells.", "contents": "Transfer of the human genes coding for thymidine kinase and galactokinase to Chinese hamster cells and human-Chinese hamster cell hybrids. Cotransfer of two linked human genes, coding for the enzymes thymidine kinase (TK) and galactokinase (Gak) was demonstrated following incubation of Chinese hamster TK-deficient cells with isolated human chromosomes. The 5 colonies which were isolated all expressed a stable TK-positive phenotype. Cotransfer of the human genes coding for TK and Gak has also been observed in experiments in which isolated human chromosomes were incubated with TK-deficient human-Chinese hamster cell hybrids. These receipient hybrids had lost all human chromosomes at the time of incubation. From these experiments, four colonies were isolated, all expressing an unstable TK-positive phenotype. Using chromosome staining techniques, the presence of human chromosomes could not be demonstrated in either of the transformed clonal lines obtained with the Chinese hamster and the hybrid recipient cells. This indicates that incorporation of only the fragment of the human chromosome 17, bearing the genes for TK and Gak, has occurred in the recipient cells."}
{"id": "PMID:204068", "title": "Adenosine kinase as a new selective marker in somatic cell genetics: isolation of adenosine kinase--deficient mouse cell lines and human--mouse hybrid cell lines containing adenosine kinase.", "content": "A new selective system for isolating somatic cell hybrids, using adenosine kinase as the selective marker, has been developed. The selective medium for forward selection (to select for cells containing adenosine kinase) contains alanosine, adenosine and uridine. To survive in the presence of alanosine, cells must have adenosine kinase in order to utilize exogenous adenosine as the sole source of AMP. Uridine is added to the selective medium to prevent the toxic effects of adenosine on cultured mammalian cells. The selective medium for reverse selection (to select for cells lacking adenosine kinase) contains 2-fluoroadenosine, an analogue of adenosine, which is converted to a toxic nucleotide by the action of adenosine kinase. Mouse mutant cell lines deficient in adenosine kinase have been derived. Human--mouse hybrid cells containing the kinase have been prepared from one of these mutant lines. Karyotype data of these hygrid lines and their adenosine kinase-minus sublines are consistent with assignment by others of the human gene for adenosine kinase on chromosome 10.", "contents": "Adenosine kinase as a new selective marker in somatic cell genetics: isolation of adenosine kinase--deficient mouse cell lines and human--mouse hybrid cell lines containing adenosine kinase. A new selective system for isolating somatic cell hybrids, using adenosine kinase as the selective marker, has been developed. The selective medium for forward selection (to select for cells containing adenosine kinase) contains alanosine, adenosine and uridine. To survive in the presence of alanosine, cells must have adenosine kinase in order to utilize exogenous adenosine as the sole source of AMP. Uridine is added to the selective medium to prevent the toxic effects of adenosine on cultured mammalian cells. The selective medium for reverse selection (to select for cells lacking adenosine kinase) contains 2-fluoroadenosine, an analogue of adenosine, which is converted to a toxic nucleotide by the action of adenosine kinase. Mouse mutant cell lines deficient in adenosine kinase have been derived. Human--mouse hybrid cells containing the kinase have been prepared from one of these mutant lines. Karyotype data of these hygrid lines and their adenosine kinase-minus sublines are consistent with assignment by others of the human gene for adenosine kinase on chromosome 10."}
{"id": "PMID:204069", "title": "T antigen and initiation of cell DNA synthesis in a temperature-sensitive mouse line transformed by an SV40tsA mutant and in heterokaryons of the transformed cells and chick erythrocytes.", "content": "The role of SV40 gene A product in initiation of cellular DNA synthesis was investigated, using a mouse kidney line [mKSA207] transformed by SV40tsA207. mKSA207 cells were temperature sensitive for growth, lost SV40 T antigen (Tag) when incubated in low serum at 40degreeC, and accumulated Tag in the cytoplasm when fed 10% serum and incubated at the nonpermissive temperature (39.7degreeC). Following serum addition, the percentage of mKSA207 cells synthesizing DNA was essentially the same at nonpermissive (39.7 degrees C) and permissive temperatures (33.5degreeC). The cells entered S phase asynchronously at both temperatures, but most cells entered S within 16 h, and before Tag accumulated. mKSA207 synchronized by a double thymidine block also synthesized DNA at 39.7degreesC and entered a second S phase. Tag-depleted or Tag-synchronized mKSA207, when fused with chick erythrocytes (CE), activated CE DNA synthesis. At nonpermissive temperatures (39.7degreesC), 40% of CE nuclei in heterokaryons with Tag-depleted mKSA207 displayed 3H-thymidine--labeled nuclei 28--40 h after fusion, when only 12% of CE nuclei were Tag+. The experiments indicate that SV40 gene A product probably does not have a direct role as initiator of cellular DNA synthesis.", "contents": "T antigen and initiation of cell DNA synthesis in a temperature-sensitive mouse line transformed by an SV40tsA mutant and in heterokaryons of the transformed cells and chick erythrocytes. The role of SV40 gene A product in initiation of cellular DNA synthesis was investigated, using a mouse kidney line [mKSA207] transformed by SV40tsA207. mKSA207 cells were temperature sensitive for growth, lost SV40 T antigen (Tag) when incubated in low serum at 40degreeC, and accumulated Tag in the cytoplasm when fed 10% serum and incubated at the nonpermissive temperature (39.7degreeC). Following serum addition, the percentage of mKSA207 cells synthesizing DNA was essentially the same at nonpermissive (39.7 degrees C) and permissive temperatures (33.5degreeC). The cells entered S phase asynchronously at both temperatures, but most cells entered S within 16 h, and before Tag accumulated. mKSA207 synchronized by a double thymidine block also synthesized DNA at 39.7degreesC and entered a second S phase. Tag-depleted or Tag-synchronized mKSA207, when fused with chick erythrocytes (CE), activated CE DNA synthesis. At nonpermissive temperatures (39.7degreesC), 40% of CE nuclei in heterokaryons with Tag-depleted mKSA207 displayed 3H-thymidine--labeled nuclei 28--40 h after fusion, when only 12% of CE nuclei were Tag+. The experiments indicate that SV40 gene A product probably does not have a direct role as initiator of cellular DNA synthesis."}
{"id": "PMID:204070", "title": "Cystosarcoma phyllodes.", "content": "Recurrence and metastases of a cystosarcoma phyllodes are poorly correlated with the histologic type and treatment used. There is some evidence, however, that the prognosis is more favorable for small tumors and minimal cellular atypism. Local excision seems to be associated with a higher incidence of recurrence of the tumor. Metastases can develop later from what appears primarily a benign, as well as a malignant, type. Mastectomy as primary treatment was not always effective in preventing the local recurrence of the tumor. If the tumor recurred after mastectomy, it gave rise to fatal metastases. The recurrence of the tumor after local excision is secondary to microscopic foci retained after enucleation. If a local excision is done, it should include a wide margin of mammary tissue around the tumor. Wide local excision, for small, slow growing and clinically benign tumors can be used as a first operation, with wider re-excision and later mastectomy if the tumor recurs. Large and rapidly growing tumors that suggest malignant disease should be treated primarily by mastectomy.", "contents": "Cystosarcoma phyllodes. Recurrence and metastases of a cystosarcoma phyllodes are poorly correlated with the histologic type and treatment used. There is some evidence, however, that the prognosis is more favorable for small tumors and minimal cellular atypism. Local excision seems to be associated with a higher incidence of recurrence of the tumor. Metastases can develop later from what appears primarily a benign, as well as a malignant, type. Mastectomy as primary treatment was not always effective in preventing the local recurrence of the tumor. If the tumor recurred after mastectomy, it gave rise to fatal metastases. The recurrence of the tumor after local excision is secondary to microscopic foci retained after enucleation. If a local excision is done, it should include a wide margin of mammary tissue around the tumor. Wide local excision, for small, slow growing and clinically benign tumors can be used as a first operation, with wider re-excision and later mastectomy if the tumor recurs. Large and rapidly growing tumors that suggest malignant disease should be treated primarily by mastectomy."}
{"id": "PMID:204071", "title": "Preoperative occlusion of the hepatic artery with isobutyl 2-cyanoacrylate for resection of the \"unresectable\" hepatic tumor.", "content": "The case of a child with an \"unresectable\" hepatic tumor is presented to introduce a new technique of preoperative selective tumor vascular occlusion by means of injection of isobutyl 2-cyanoacrylate on the morning of surgical resection. This technique provides a well demarcated, significantly smaller, and relatively avascular field, allowing for a safe and total removal of the hepatic neoplasm.", "contents": "Preoperative occlusion of the hepatic artery with isobutyl 2-cyanoacrylate for resection of the \"unresectable\" hepatic tumor. The case of a child with an \"unresectable\" hepatic tumor is presented to introduce a new technique of preoperative selective tumor vascular occlusion by means of injection of isobutyl 2-cyanoacrylate on the morning of surgical resection. This technique provides a well demarcated, significantly smaller, and relatively avascular field, allowing for a safe and total removal of the hepatic neoplasm."}
{"id": "PMID:204072", "title": "Granulocyte collagenase and elastase and the plasma protease inhibitors in human pus.", "content": "Granulocyte collagenase and elastase was demonstrated in human pus using specific antisera. The enzymes were complexed by alpha1-antitrypsin and alpha2-macroglobulin but also were present as free proteases. All purulent exudates showed free elastolytic and collagenolytic activity.", "contents": "Granulocyte collagenase and elastase and the plasma protease inhibitors in human pus. Granulocyte collagenase and elastase was demonstrated in human pus using specific antisera. The enzymes were complexed by alpha1-antitrypsin and alpha2-macroglobulin but also were present as free proteases. All purulent exudates showed free elastolytic and collagenolytic activity."}
{"id": "PMID:204075", "title": "Type IIa hyperlipoproteinemia and the HLA system.", "content": "The comparative study of a control group made up of 340 healthy subjects, a group of 100 unrelated patients, all showing signs of type II hyperlipoproteinemia and a family of 15 members covering three successive generations, brings to light the highly significant increase of the recurrence of HLA Bw17 antigen and the increase in frequency of HLA Bw35 antigen.", "contents": "Type IIa hyperlipoproteinemia and the HLA system. The comparative study of a control group made up of 340 healthy subjects, a group of 100 unrelated patients, all showing signs of type II hyperlipoproteinemia and a family of 15 members covering three successive generations, brings to light the highly significant increase of the recurrence of HLA Bw17 antigen and the increase in frequency of HLA Bw35 antigen."}
{"id": "PMID:204078", "title": "Massive intramedullary globules in IgA monoclonal gammopathy associated with gastric carcinoma.", "content": "The bone marrow of a patient with IgA monoclonal gammopathy associated with gastric carcinoma was massively infiltrated with extracellular globules of varying sizes from 2 to 110 micron. These exposed globules were not found in the metastatic lesions heavily infiltrated with plasma cells, but were exclusively confined to the bone marrow. They were indistinguishable from Russell bodies and composed of monoclonal immunoglobulin (IgA, lambda). Of interest is the fact that, despite a small number of plasma cells, there was an intramedullary extensive infiltration of exposed globules. The following conditions may be related to these changes. (1) The globules were not removed rapidly by effectual phagocytosis. (2) The environment of the bone marrow may be favorable for their remaining. In our case, however, the possibility that the plasma cells around the tumor were not of the same clonal origin as the marrow plasma cells cannot be ruled out. (3) The marrow plasma cells may produce immunoglobulin more vigorously, whereas their survival time be shorter than usual. As a result, these exposed globules released on the death of the cells accumulated massively in the bone marrow.", "contents": "Massive intramedullary globules in IgA monoclonal gammopathy associated with gastric carcinoma. The bone marrow of a patient with IgA monoclonal gammopathy associated with gastric carcinoma was massively infiltrated with extracellular globules of varying sizes from 2 to 110 micron. These exposed globules were not found in the metastatic lesions heavily infiltrated with plasma cells, but were exclusively confined to the bone marrow. They were indistinguishable from Russell bodies and composed of monoclonal immunoglobulin (IgA, lambda). Of interest is the fact that, despite a small number of plasma cells, there was an intramedullary extensive infiltration of exposed globules. The following conditions may be related to these changes. (1) The globules were not removed rapidly by effectual phagocytosis. (2) The environment of the bone marrow may be favorable for their remaining. In our case, however, the possibility that the plasma cells around the tumor were not of the same clonal origin as the marrow plasma cells cannot be ruled out. (3) The marrow plasma cells may produce immunoglobulin more vigorously, whereas their survival time be shorter than usual. As a result, these exposed globules released on the death of the cells accumulated massively in the bone marrow."}
{"id": "PMID:204082", "title": "A radioimmunoassay of plasma unconjugated and conjugated estetrol.", "content": "A radioimmunoassay for the measurement of both unconjugated and conjugaged estetrol in plasma has been developed. The antiserum obtained after 6 months of immunization with 6-oxoestetrol-6-(O-carboxy-methyl)oxim-BSA was used at a final dilution of 1:90,000 and showed almost no cross reaction with other steroids except for estriol at 1.24%. Esterol-glucosiduronate was synthesized by incubating with adrenalectomized rat liver homogenate and uridine diphosphoglucuronic acid. Then, plasma estetrol-glucosiduronate was measured in the same manner for unconjugated estetrol after hydrolysis with beta-glucuronidase. Sephadex LH-20 column chromatography (7X110 mm, benzene:methanol, 85:15) was employed for accurate assessment. The sensitivity was 10 pg and the smallest amount measurable was 40 pg/sample. The method bland was consistently negligible. The intra and inter assay precision was 11.8% and 14.2% for unconjugated estetrol and that for estetrol-glucosiduronate was 13.5% and 17.1%.", "contents": "A radioimmunoassay of plasma unconjugated and conjugated estetrol. A radioimmunoassay for the measurement of both unconjugated and conjugaged estetrol in plasma has been developed. The antiserum obtained after 6 months of immunization with 6-oxoestetrol-6-(O-carboxy-methyl)oxim-BSA was used at a final dilution of 1:90,000 and showed almost no cross reaction with other steroids except for estriol at 1.24%. Esterol-glucosiduronate was synthesized by incubating with adrenalectomized rat liver homogenate and uridine diphosphoglucuronic acid. Then, plasma estetrol-glucosiduronate was measured in the same manner for unconjugated estetrol after hydrolysis with beta-glucuronidase. Sephadex LH-20 column chromatography (7X110 mm, benzene:methanol, 85:15) was employed for accurate assessment. The sensitivity was 10 pg and the smallest amount measurable was 40 pg/sample. The method bland was consistently negligible. The intra and inter assay precision was 11.8% and 14.2% for unconjugated estetrol and that for estetrol-glucosiduronate was 13.5% and 17.1%."}
{"id": "PMID:204086", "title": "Serological evidence of bluetongue in game animals in Botswana.", "content": "Using the Agar Gel Precipitin technique the sera of 397 African buffalo (Syncerus caffer) and 90 sera of other common game species were examined for bluetongue antibodies. Of the adult buffalo 283 out of 325 (87 per cent) were positive. Buffalo calves were positive in 25 out of 72 cases (35 per cent). Positive reactions were also recorded in lechwe (Kobus leche), tsessebe (Damaliscus lunatus), red hartebeeste (Alcelaphus buselaphus), gemsbok (Oryx gazella), sable (Hippotragus niger) and impala (Aepyceros melampus).", "contents": "Serological evidence of bluetongue in game animals in Botswana. Using the Agar Gel Precipitin technique the sera of 397 African buffalo (Syncerus caffer) and 90 sera of other common game species were examined for bluetongue antibodies. Of the adult buffalo 283 out of 325 (87 per cent) were positive. Buffalo calves were positive in 25 out of 72 cases (35 per cent). Positive reactions were also recorded in lechwe (Kobus leche), tsessebe (Damaliscus lunatus), red hartebeeste (Alcelaphus buselaphus), gemsbok (Oryx gazella), sable (Hippotragus niger) and impala (Aepyceros melampus)."}
{"id": "PMID:204087", "title": "[Biochemical properties of aging of rat periodontium].", "content": "The content of proteins and nucleic acids and activity of acid and alkaline proteases, RNases, phosphatases and alpha-amylase were studied in the gum and alveolar bone or rats at the age of 1, 3, 6, 12, 18 and 24 months. It is found that a degree of periodontal atrophy strongly and directly correlates with the age of rats. The concentration of DNA and RNA in alveolar bone and of RNA in gum decreases with the age. The hydroxyproline content of periodontal tissues continuously increases till the age of 18th month and then considerably decreases. The activity of trypsin-like proteases, cathepsins and alkaline RNase in periodontal tissues increases reaching the maximum at the age of 6-18 months, and the activity of alkaline phosphatase decreases in the process of aging.", "contents": "[Biochemical properties of aging of rat periodontium]. The content of proteins and nucleic acids and activity of acid and alkaline proteases, RNases, phosphatases and alpha-amylase were studied in the gum and alveolar bone or rats at the age of 1, 3, 6, 12, 18 and 24 months. It is found that a degree of periodontal atrophy strongly and directly correlates with the age of rats. The concentration of DNA and RNA in alveolar bone and of RNA in gum decreases with the age. The hydroxyproline content of periodontal tissues continuously increases till the age of 18th month and then considerably decreases. The activity of trypsin-like proteases, cathepsins and alkaline RNase in periodontal tissues increases reaching the maximum at the age of 6-18 months, and the activity of alkaline phosphatase decreases in the process of aging."}
{"id": "PMID:204088", "title": "[Study of electron transfer in the NADH-vitamin K-cytochrome c system].", "content": "K-group vitamins, menadion and phylloquinone are shown to be able to transfer transmembrane electron from NAD.H onto cytochorme c localized inside lyposomes. Menadion reduces 60-70% of \"endogenous\" protein and phylloquinone--20--30%. FMN being added to the incubation medium increases considerably the rate of cytochrome c reduction, the quantity of \"endogenous\" protein remains unchanged.", "contents": "[Study of electron transfer in the NADH-vitamin K-cytochrome c system]. K-group vitamins, menadion and phylloquinone are shown to be able to transfer transmembrane electron from NAD.H onto cytochorme c localized inside lyposomes. Menadion reduces 60-70% of \"endogenous\" protein and phylloquinone--20--30%. FMN being added to the incubation medium increases considerably the rate of cytochrome c reduction, the quantity of \"endogenous\" protein remains unchanged."}
{"id": "PMID:204089", "title": "[Activity of glycolysis enzymes in kidneys, blood serum and urine with toxicity of certain segments of the nephron].", "content": "The activity of hexokinase, glycose-6-phosphatase, phosphofructokinase, fructose diphosphate aldolase and ketose-1-phosphate aldolase was studied in kidneys, blood serum and urine or rats, the proximal and distal areas of their nephron being affected with the chemical substances. A pronounced decrease in the activity of the mentioned enzymes in the renal tissue was greater with afection of the nephron proximal area. The activity of the mentioned enzymes in urine, vice versa, increases sharply and in blood serum it was almost unchanges (exception for keto-1-phosphate aldolase). The pronounced enzyme uria may reflect the deep changes in epithelium cells of canals, especially of proximal ones where the enzymes under study are mainly localized.", "contents": "[Activity of glycolysis enzymes in kidneys, blood serum and urine with toxicity of certain segments of the nephron]. The activity of hexokinase, glycose-6-phosphatase, phosphofructokinase, fructose diphosphate aldolase and ketose-1-phosphate aldolase was studied in kidneys, blood serum and urine or rats, the proximal and distal areas of their nephron being affected with the chemical substances. A pronounced decrease in the activity of the mentioned enzymes in the renal tissue was greater with afection of the nephron proximal area. The activity of the mentioned enzymes in urine, vice versa, increases sharply and in blood serum it was almost unchanges (exception for keto-1-phosphate aldolase). The pronounced enzyme uria may reflect the deep changes in epithelium cells of canals, especially of proximal ones where the enzymes under study are mainly localized."}
{"id": "PMID:204096", "title": "An electron microscopic study of experimentally-induced HEV encephalitis.", "content": "A gnobiotic piglet, was inoculated intracerebrally with hemagglutinating encephalomyelitis virus (strain VW572). Mononuclear cells formed vascular cuffs and were disseminated in the brain parenchyma. A few neurons were surrounded by the same kind of cells. Virus particles morphologically similar to coronavirus particles were found in the cytoplasm of both chromatolytic light neurons and hyperchromic dark neurons. The particles were in vesicles of distended endoplasmic reticulum and in the hypertrophied Golgi apparatus.", "contents": "An electron microscopic study of experimentally-induced HEV encephalitis. A gnobiotic piglet, was inoculated intracerebrally with hemagglutinating encephalomyelitis virus (strain VW572). Mononuclear cells formed vascular cuffs and were disseminated in the brain parenchyma. A few neurons were surrounded by the same kind of cells. Virus particles morphologically similar to coronavirus particles were found in the cytoplasm of both chromatolytic light neurons and hyperchromic dark neurons. The particles were in vesicles of distended endoplasmic reticulum and in the hypertrophied Golgi apparatus."}
{"id": "PMID:204097", "title": "Hypervitaminosis D and metastatic pulmonary calcification in a cow.", "content": "The history, clinical signs and post mortem findings in a cow with metastatic pulmonary calcification and calcific arteriosclerosis after vitamin D3 treatment are described.", "contents": "Hypervitaminosis D and metastatic pulmonary calcification in a cow. The history, clinical signs and post mortem findings in a cow with metastatic pulmonary calcification and calcific arteriosclerosis after vitamin D3 treatment are described."}
{"id": "PMID:204103", "title": "[Immunoprophylaxis of infectious bovine rhinotracheitis].", "content": "The live attenuated vaccine against infectious rhinotracheitis (LAV), the live trivaccine against infectious rhinotracheitis (LT), the concentrated etanolsaponin vaccine against infectious rhinotracheitis (CESV) and the ethanol-saponin vaccine against infectious rhinotracheitis (ESV) can all be used as immunoprophylactic means in the control of infectious rhinotracheitis in cattle. The first two live vaccines are applied to calves in infection foci, and the two inactivated vaccines are used with cows. The comparative testing of CESV and ESV in experimental conditions on calves has shown that the first possesses higher immunogenicity--used in a twice lower dose it produces several times higher level of the neutralizing antibodies against the infectious rhinotracheitis virus. The use of LAV and LT in the practice under the conditions of established infections of infectious rhinotracheitis in calves has given good results. The immunization of calves at the immediate menace of this infection has lowered the morbidity rate, and death cases were no longer observed. The use of CESV and ESV with pregnant cows on a prophylactic basis against infectious rhinotracheitis has also given good results manifested in the full suppression of abortions.", "contents": "[Immunoprophylaxis of infectious bovine rhinotracheitis]. The live attenuated vaccine against infectious rhinotracheitis (LAV), the live trivaccine against infectious rhinotracheitis (LT), the concentrated etanolsaponin vaccine against infectious rhinotracheitis (CESV) and the ethanol-saponin vaccine against infectious rhinotracheitis (ESV) can all be used as immunoprophylactic means in the control of infectious rhinotracheitis in cattle. The first two live vaccines are applied to calves in infection foci, and the two inactivated vaccines are used with cows. The comparative testing of CESV and ESV in experimental conditions on calves has shown that the first possesses higher immunogenicity--used in a twice lower dose it produces several times higher level of the neutralizing antibodies against the infectious rhinotracheitis virus. The use of LAV and LT in the practice under the conditions of established infections of infectious rhinotracheitis in calves has given good results. The immunization of calves at the immediate menace of this infection has lowered the morbidity rate, and death cases were no longer observed. The use of CESV and ESV with pregnant cows on a prophylactic basis against infectious rhinotracheitis has also given good results manifested in the full suppression of abortions."}
{"id": "PMID:204104", "title": "[Virus-neutralizing antibodies in the colostrum and milk of brood sows vaccinated with an ethanol vaccine against Aujeszky's disease virus].", "content": "The experiment was carried out with five pregnant sows vaccinated with an etanol vaccine against the Aujeszky's disease virus. Studies was the level of virus-neutralizing antibodies in the blood, colostrum and milk serum of the sows as in the serum of their piglets. Virus-neutralizing antibodies were contained in high titers both in the blood, colostrum, and milk serum of the sows and in the serum of the offsprings. The titer of the passively acquired antibodies in the blood serum of the sucklings proved directly dependable on the titer of the colostral antibody level of their dams. The use is suggested of colostral sera for the evaluation of the immune status of sows in the breeding herds that are disease-free and vaccinated against the virus of Aujeszky's disease.", "contents": "[Virus-neutralizing antibodies in the colostrum and milk of brood sows vaccinated with an ethanol vaccine against Aujeszky's disease virus]. The experiment was carried out with five pregnant sows vaccinated with an etanol vaccine against the Aujeszky's disease virus. Studies was the level of virus-neutralizing antibodies in the blood, colostrum and milk serum of the sows as in the serum of their piglets. Virus-neutralizing antibodies were contained in high titers both in the blood, colostrum, and milk serum of the sows and in the serum of the offsprings. The titer of the passively acquired antibodies in the blood serum of the sucklings proved directly dependable on the titer of the colostral antibody level of their dams. The use is suggested of colostral sera for the evaluation of the immune status of sows in the breeding herds that are disease-free and vaccinated against the virus of Aujeszky's disease."}
{"id": "PMID:204105", "title": "Asteroid bodies: derivatives of the cytosphere. An electron microscopic contribution to the pathology of the cytocentre.", "content": "An electron microscopic study of asteroid bodies in granulomatous diseases of man, in particular in sarcoidosis and foreign body reactions, has led to the following conclusions. 1. Asteroid cytoplasmic inclusions are composed of organic proteineous structures. The body and arms of the stars consist mainly of longitudinally orientated, partially helically wound, collagen free, microfilaments with a diameter of approximately 50 A. Microtubules participate in their composition to a lesser degree. The filaments intertwine in various directions within the corpus of the stars. 2. Deeply osmiophilic compact structures, considered to represent condensation forms of protein, are consistently present within the body of the stars. These structures are partially granular and partially ring-shaped; in the latter case, transverse sections of tubules are noted. Since it is disputed whether they constitute procentrioles or postcentrioles, they are best referred to as paracentrioles. 3. The asteroid bodies are derivatives of the cytosphere, thus relating, in the broad sense, to the microfilamentous and microtubular apparatus of the cell. 4. The asteroid bodies in multinucleated giant cells participate in the spatial compartmentalization of the cytoplasmic content and nuclei. The sphere, aided by the centrioles, induces the formation of the mitotic spindle and, in addition, function as an organizing system of the cell. 5. The light microscopical periastral clear zone does not correspond to a fluid space. Rather, it consists of closely packed accumulations of laminated and whorled myelin figures, which are derived from the degradation of lipoid substances.", "contents": "Asteroid bodies: derivatives of the cytosphere. An electron microscopic contribution to the pathology of the cytocentre. An electron microscopic study of asteroid bodies in granulomatous diseases of man, in particular in sarcoidosis and foreign body reactions, has led to the following conclusions. 1. Asteroid cytoplasmic inclusions are composed of organic proteineous structures. The body and arms of the stars consist mainly of longitudinally orientated, partially helically wound, collagen free, microfilaments with a diameter of approximately 50 A. Microtubules participate in their composition to a lesser degree. The filaments intertwine in various directions within the corpus of the stars. 2. Deeply osmiophilic compact structures, considered to represent condensation forms of protein, are consistently present within the body of the stars. These structures are partially granular and partially ring-shaped; in the latter case, transverse sections of tubules are noted. Since it is disputed whether they constitute procentrioles or postcentrioles, they are best referred to as paracentrioles. 3. The asteroid bodies are derivatives of the cytosphere, thus relating, in the broad sense, to the microfilamentous and microtubular apparatus of the cell. 4. The asteroid bodies in multinucleated giant cells participate in the spatial compartmentalization of the cytoplasmic content and nuclei. The sphere, aided by the centrioles, induces the formation of the mitotic spindle and, in addition, function as an organizing system of the cell. 5. The light microscopical periastral clear zone does not correspond to a fluid space. Rather, it consists of closely packed accumulations of laminated and whorled myelin figures, which are derived from the degradation of lipoid substances."}
{"id": "PMID:204112", "title": "[Gene frequencies of both forms of galactosaemia in the western Hungarian province of Vas (author's transl)].", "content": "The two enzymes of galactose metabolism, namely galactokinase and galactose-1-phosphate uridyltransferase (Gal-1-PUT), were measured in 3653 subjects aged 7 months to 84 years in der to obtain the incidence of the gene deficiency causing galactosaemia in the Western Hungarian province of Vas. To date nothing is known about these frequencies in this particular region. It was of special interest whether these enzyme defects are to be found more frequently in gypsies than in a comparable population of West Hungary. The frequency of homozygous Gal-1-PUT deficiency amounts to 1:23,500; the respective incidence of galactokinase deficiency is 1:64,000. Both enzyme deficiencies in this province are not higher than in other countries. Considerable differences were established in the gene frequencies in individual areas and for various groups of subjects with variations from 1:30,000 to 1: 127,000 for galactokinase deficiency and from 1:5,300 to 1:81,000 for Gal-1-PUT deficiency. Neither gene deficiency occurred more frequently in gypsies than in the general population. This study demonstrates that the results of such analyses are relevant only to the investigated region and the greatest possible number of subjects must be taken in order to draw reliable conclusions.", "contents": "[Gene frequencies of both forms of galactosaemia in the western Hungarian province of Vas (author's transl)]. The two enzymes of galactose metabolism, namely galactokinase and galactose-1-phosphate uridyltransferase (Gal-1-PUT), were measured in 3653 subjects aged 7 months to 84 years in der to obtain the incidence of the gene deficiency causing galactosaemia in the Western Hungarian province of Vas. To date nothing is known about these frequencies in this particular region. It was of special interest whether these enzyme defects are to be found more frequently in gypsies than in a comparable population of West Hungary. The frequency of homozygous Gal-1-PUT deficiency amounts to 1:23,500; the respective incidence of galactokinase deficiency is 1:64,000. Both enzyme deficiencies in this province are not higher than in other countries. Considerable differences were established in the gene frequencies in individual areas and for various groups of subjects with variations from 1:30,000 to 1: 127,000 for galactokinase deficiency and from 1:5,300 to 1:81,000 for Gal-1-PUT deficiency. Neither gene deficiency occurred more frequently in gypsies than in the general population. This study demonstrates that the results of such analyses are relevant only to the investigated region and the greatest possible number of subjects must be taken in order to draw reliable conclusions."}
{"id": "PMID:204111", "title": "Cholesterol metabolism in man.", "content": "Recent investigations on cholesterol metabolism in man have led to new insights into diseases associated with abnormal accumulations of cholesterol in plasma (hypercholesterolemia), arterial tissues (atherosclerosis) and biliary tract (gallstones). Regulation of cholesterol synthesis under the influence of dietary and plasma cholesterol, may play a crucial role in determining biliary and tissue concentrations of this sterol. Plasma concentrations, on the other hand, appear to be controlled by complex mechanisms for secretion, transformation and removal of plasma lipoproteins. The recent identification of specific cellular receptors for uptake of plasma lipoproteins represents a significant advance for the understanding of regulation of both plasma and tissue concentrations, and possibly of the basic mechanisms underlying accumulation of cholesterol in atherosclerotic plaques.", "contents": "Cholesterol metabolism in man. Recent investigations on cholesterol metabolism in man have led to new insights into diseases associated with abnormal accumulations of cholesterol in plasma (hypercholesterolemia), arterial tissues (atherosclerosis) and biliary tract (gallstones). Regulation of cholesterol synthesis under the influence of dietary and plasma cholesterol, may play a crucial role in determining biliary and tissue concentrations of this sterol. Plasma concentrations, on the other hand, appear to be controlled by complex mechanisms for secretion, transformation and removal of plasma lipoproteins. The recent identification of specific cellular receptors for uptake of plasma lipoproteins represents a significant advance for the understanding of regulation of both plasma and tissue concentrations, and possibly of the basic mechanisms underlying accumulation of cholesterol in atherosclerotic plaques."}
{"id": "PMID:204114", "title": "Sarcoidosis therapy with cortisone and ACTH--the role of ACTH therapy.", "content": "Out of 58 sarcoidosis patients 55 were treated successfully with a prednisolone therapy lasting one to two years. The high initial dosis of 40 mg daily has been maintained for at least 3 months. In case of intolerance or inefficiency of corticosteroid therapy a treatment with synthetic ACTH either in combination with corticosteroids or only ACTH was applied to 23 patients. The positive experiences of other authors were confirmed. Synthetic ACTH (1 mg) injected intramuscularly every third day did not cause any side-effects. ACTH can be employed not only in combination with corticosteroids, but it can also substitute them in special clinical cases.", "contents": "Sarcoidosis therapy with cortisone and ACTH--the role of ACTH therapy. Out of 58 sarcoidosis patients 55 were treated successfully with a prednisolone therapy lasting one to two years. The high initial dosis of 40 mg daily has been maintained for at least 3 months. In case of intolerance or inefficiency of corticosteroid therapy a treatment with synthetic ACTH either in combination with corticosteroids or only ACTH was applied to 23 patients. The positive experiences of other authors were confirmed. Synthetic ACTH (1 mg) injected intramuscularly every third day did not cause any side-effects. ACTH can be employed not only in combination with corticosteroids, but it can also substitute them in special clinical cases."}
{"id": "PMID:204115", "title": "Effect of AMP on acute carbon-tetrachloride hepatotoxicity.", "content": "The effect of carbon-tetrachloride poisoning and the protection caused by AMP were studied. A single dose of CCl4 has resulted in a rapid development of a fatty liver, a considerable increase in serum enzymes, glutamic oxalacetic and pyruvic transaminases as well as serum-alkaline phosphatase. Total serum protein showed a tendency to decrease accompanied by a decrease in A/G ratio. Administration of adenosine-5-monophosphate prevented the increase in serum-alkaline phosphatase and increased the A/G ratio. There was, however, a slight but significant decrease in serum GOT and GPT within the 24-hrs. period of study, but it remained still higher than that of the control. AMP lowered liver fat without complete protection against the development of fatty liver.", "contents": "Effect of AMP on acute carbon-tetrachloride hepatotoxicity. The effect of carbon-tetrachloride poisoning and the protection caused by AMP were studied. A single dose of CCl4 has resulted in a rapid development of a fatty liver, a considerable increase in serum enzymes, glutamic oxalacetic and pyruvic transaminases as well as serum-alkaline phosphatase. Total serum protein showed a tendency to decrease accompanied by a decrease in A/G ratio. Administration of adenosine-5-monophosphate prevented the increase in serum-alkaline phosphatase and increased the A/G ratio. There was, however, a slight but significant decrease in serum GOT and GPT within the 24-hrs. period of study, but it remained still higher than that of the control. AMP lowered liver fat without complete protection against the development of fatty liver."}
{"id": "PMID:204117", "title": "[Influence of hemodialysis, heparin and protamin on the pre-beta fraction of lipoproteins in patients with chronic kidney failure].", "content": "The spectrum of lipoproteins in the serum and the blood clotting time was examined in 19 dialyzed and 5 non-dialyzed patients with chronic renal failure. Compared were the values obtained in hemodialysis with intermittent and regional heparinization and the changes after the application of heparin in hemodialysis and beside it. In non-dialyzed and dialyzed patients in interdialyzation period were studied the changes of given parameters which occur after heparin and protamin application. Out of the results of this examination it follows that: 1. the most significant factor causing the changes of lipoprotein spectrum in the serum during hemodialysis is heparin. 2. the effect of protamin upon the lipoprotein spectrum during hemodialysis cannot be explained only by the neutralisation of heparin effect. 3. beside heparin and protamin in the spectrum changes of lipoproteins during hemodialysis also other factors are participant that are concerned with hemodialysis.", "contents": "[Influence of hemodialysis, heparin and protamin on the pre-beta fraction of lipoproteins in patients with chronic kidney failure]. The spectrum of lipoproteins in the serum and the blood clotting time was examined in 19 dialyzed and 5 non-dialyzed patients with chronic renal failure. Compared were the values obtained in hemodialysis with intermittent and regional heparinization and the changes after the application of heparin in hemodialysis and beside it. In non-dialyzed and dialyzed patients in interdialyzation period were studied the changes of given parameters which occur after heparin and protamin application. Out of the results of this examination it follows that: 1. the most significant factor causing the changes of lipoprotein spectrum in the serum during hemodialysis is heparin. 2. the effect of protamin upon the lipoprotein spectrum during hemodialysis cannot be explained only by the neutralisation of heparin effect. 3. beside heparin and protamin in the spectrum changes of lipoproteins during hemodialysis also other factors are participant that are concerned with hemodialysis."}
{"id": "PMID:204118", "title": "[Constellation of lipoproteins in patients with hyperlipoproteinemia and in rabbits fed a cholesterol diet with reference to vascular permeability].", "content": "By feeding of rabbits with cholesterol a hyperlipoproteinaemia (HLP) was created and the changes of the cholesterol and triglyceride (TGL) level were compared with the changes of the portions of the pre-beta- and beta-lipoproteins. The electrophoresis with a gel of agar-agarose are more suitable for the densitometric evaluation than electrophoresis with cellulose acetate films. Tests with Evan's blue of the angiopermeability of rabbits feeded with cholesterol showed that the permeability of the cutaneous vessels decreased strikingly during test period, while a change of the permeability of the aorta was not to be proved under the conditions of our tests. HLP patients had been treated with clofibrinic acid, nicotinic acid derivatives and metabolism basic diet for 3 years. The cholesterol and TGL values as well as the pre-beta-/beta-lipoprotein quotients have been determined before and after treatment. The pre-beta-/beta-lipoprotein quotient has proved as suitable complementary parameter for pursuit of the therapeutic result with HLP patients. The changes of the quotients corresponded well with the found changes of the HLP types. The decrease of the TGL content of HLP patients of the type IV or IIb being treated with metabolism basic diet or clofibrinic acid may be estimated (with nearly constant cholesterol level) from the per cent decrease of the pre-beta-/beta-quotient.", "contents": "[Constellation of lipoproteins in patients with hyperlipoproteinemia and in rabbits fed a cholesterol diet with reference to vascular permeability]. By feeding of rabbits with cholesterol a hyperlipoproteinaemia (HLP) was created and the changes of the cholesterol and triglyceride (TGL) level were compared with the changes of the portions of the pre-beta- and beta-lipoproteins. The electrophoresis with a gel of agar-agarose are more suitable for the densitometric evaluation than electrophoresis with cellulose acetate films. Tests with Evan's blue of the angiopermeability of rabbits feeded with cholesterol showed that the permeability of the cutaneous vessels decreased strikingly during test period, while a change of the permeability of the aorta was not to be proved under the conditions of our tests. HLP patients had been treated with clofibrinic acid, nicotinic acid derivatives and metabolism basic diet for 3 years. The cholesterol and TGL values as well as the pre-beta-/beta-lipoprotein quotients have been determined before and after treatment. The pre-beta-/beta-lipoprotein quotient has proved as suitable complementary parameter for pursuit of the therapeutic result with HLP patients. The changes of the quotients corresponded well with the found changes of the HLP types. The decrease of the TGL content of HLP patients of the type IV or IIb being treated with metabolism basic diet or clofibrinic acid may be estimated (with nearly constant cholesterol level) from the per cent decrease of the pre-beta-/beta-quotient."}
{"id": "PMID:204119", "title": "Structural changes on Entamoeba histolytica trophozoites after cryopreservation in liquid nitrogen.", "content": "Trophozoites of Entamoeba histolytica cultures which had been deep-frozen in the presence of 5% DMSO, along with untreated cells and cells treated with DMSO (5%), were examined for fine-structural changes. After deep-freezing in liquid nitrogen only a few amoebae exhibited normal nuclear and cytoplasmic structure. One frequently observed but unspecific finding pertaining to recovered cells is the separation of the cytoplasm into large vacuolated (coarse-granular) and electron-optically fine-granular (hyaline) zones. The glycogen which normally lies in the cytoplasm is always eluted. In many cases numerous short RNP helices are scattered unevenly in the vesicular plasma, but they are also found in larger masses adjacent to the membranes of still intact and already damaged nuclei. Moderately damaged nuclei have a poorly folded membrane and their chromatin is markedly denatured. More heavily damaged nuclei have a membrane which has partly fibrillated or ruptured and then formed conspicuous folds, where the nuclear membrane has ruptured nucleoplasmic remnants of chromatin and button-like bodies appear to pour into the surrounding cytoplasm. The final destruction of the cell is marked by coalescing autolytic zones, first in the vacuolated and later in the fine-granular cytoplasm. Finally only remnants of the nuclear membrane and of the membranes of numerous vacuoles remain. It is assumed that most of the changes in the cytoplasm are of a secondary nature and are caused by the early functional disturbance of the nucleus.", "contents": "Structural changes on Entamoeba histolytica trophozoites after cryopreservation in liquid nitrogen. Trophozoites of Entamoeba histolytica cultures which had been deep-frozen in the presence of 5% DMSO, along with untreated cells and cells treated with DMSO (5%), were examined for fine-structural changes. After deep-freezing in liquid nitrogen only a few amoebae exhibited normal nuclear and cytoplasmic structure. One frequently observed but unspecific finding pertaining to recovered cells is the separation of the cytoplasm into large vacuolated (coarse-granular) and electron-optically fine-granular (hyaline) zones. The glycogen which normally lies in the cytoplasm is always eluted. In many cases numerous short RNP helices are scattered unevenly in the vesicular plasma, but they are also found in larger masses adjacent to the membranes of still intact and already damaged nuclei. Moderately damaged nuclei have a poorly folded membrane and their chromatin is markedly denatured. More heavily damaged nuclei have a membrane which has partly fibrillated or ruptured and then formed conspicuous folds, where the nuclear membrane has ruptured nucleoplasmic remnants of chromatin and button-like bodies appear to pour into the surrounding cytoplasm. The final destruction of the cell is marked by coalescing autolytic zones, first in the vacuolated and later in the fine-granular cytoplasm. Finally only remnants of the nuclear membrane and of the membranes of numerous vacuoles remain. It is assumed that most of the changes in the cytoplasm are of a secondary nature and are caused by the early functional disturbance of the nucleus."}
{"id": "PMID:204121", "title": "Carcinoma of the lung: the view today.", "content": "The present epidemic of carcinoma of the lung is a consequence of society's indulence of cigarette smoking. Most of the progress in treatment has resulted from more accurate staging of the cancer at the time of diagnosis and the selection of the safest therapy. Future progress hinges on the public health measures to stop smoking, and to a much lesser degree on earlier diagnosis and advances in radiotherapy and chemotherapy.", "contents": "Carcinoma of the lung: the view today. The present epidemic of carcinoma of the lung is a consequence of society's indulence of cigarette smoking. Most of the progress in treatment has resulted from more accurate staging of the cancer at the time of diagnosis and the selection of the safest therapy. Future progress hinges on the public health measures to stop smoking, and to a much lesser degree on earlier diagnosis and advances in radiotherapy and chemotherapy."}
{"id": "PMID:204129", "title": "[Organic lesions after application of hashish in rats and rabbits (author's transl)].", "content": "Toxic lesions were found in liver, kidney and brain of rats and rabbits after oral application of hashish for 7 or 30 days. The brain tissue showed hyperemia and edema. The cerebral cortex, brain stem and cerebellum contained ganglion cells with eccentric nuclei and an icreased number of nucleoli. Different stages of cell lesions could be distinguished by nuclear vacuoles, pyknosis and karyolysis. The cytoplasma was loosened and showed numerous vacuoles. In the kidney we found, besides interstitial hemorrhage, cloudy swelling of the proximal tubules with vacuolous degeneration and nuclear pyknosis and karyolysis in all stages. The glomeruli were often enlarged with thickening of Bowman's capsule and surrounding cellular infiltration with cell fragments. The liver cells showed irregularities of nuclei and vacuolated nuclei, plasma vacuoles and cell necrosis. Infiltrations of round cells at the portal-biliary areas were usually combined with an activation of the Kupffer cells and intracellular bile stasis.", "contents": "[Organic lesions after application of hashish in rats and rabbits (author's transl)]. Toxic lesions were found in liver, kidney and brain of rats and rabbits after oral application of hashish for 7 or 30 days. The brain tissue showed hyperemia and edema. The cerebral cortex, brain stem and cerebellum contained ganglion cells with eccentric nuclei and an icreased number of nucleoli. Different stages of cell lesions could be distinguished by nuclear vacuoles, pyknosis and karyolysis. The cytoplasma was loosened and showed numerous vacuoles. In the kidney we found, besides interstitial hemorrhage, cloudy swelling of the proximal tubules with vacuolous degeneration and nuclear pyknosis and karyolysis in all stages. The glomeruli were often enlarged with thickening of Bowman's capsule and surrounding cellular infiltration with cell fragments. The liver cells showed irregularities of nuclei and vacuolated nuclei, plasma vacuoles and cell necrosis. Infiltrations of round cells at the portal-biliary areas were usually combined with an activation of the Kupffer cells and intracellular bile stasis."}
{"id": "PMID:204131", "title": "[Failure in the treatment of carcinoma of the colon and rectum in connection with the operative technique (author's transl)].", "content": "Colonic and rectal anastomoses are more subject to leakage than anastomoses in other parts of the gastrointestinal tract. The mortality is high. Many aetiologic factors are connected with the operative technique. The great role of collagenase in the colon which increases during an infection is a cause for an anastomotic break-down.", "contents": "[Failure in the treatment of carcinoma of the colon and rectum in connection with the operative technique (author's transl)]. Colonic and rectal anastomoses are more subject to leakage than anastomoses in other parts of the gastrointestinal tract. The mortality is high. Many aetiologic factors are connected with the operative technique. The great role of collagenase in the colon which increases during an infection is a cause for an anastomotic break-down."}
{"id": "PMID:204132", "title": "[Cryosurgical treatment of malignant tumors in the cerebral hemispheres].", "content": "In 35 patients with deep-lying and medial gliomas (25 cases of glioblastoma multiforma, 10 cases of dedifferentiated astrocytoma), stereotactic cryodestructions were performed after preceding biopsies. Diagnosis was made in the usual manner, mainly by means of angiography. Sites of action were the tumour mass proper and the blood supply zones. In some cases, partial removal of the tumour was carried out in the usual way before or after cryodestruction. There are 3 kinds of further development after cryodestruction: regression, slow progression and rapid progression. Progression was found in 14 patients; 9 patients died within 2 weeks after the operation. In their cases, cryodestruction was by far insufficient. Dedifferentiated astrocytomas showed more a regressive behaviour than multiform glioblastomas. The possibility of local chemotherapy was also utilised.", "contents": "[Cryosurgical treatment of malignant tumors in the cerebral hemispheres]. In 35 patients with deep-lying and medial gliomas (25 cases of glioblastoma multiforma, 10 cases of dedifferentiated astrocytoma), stereotactic cryodestructions were performed after preceding biopsies. Diagnosis was made in the usual manner, mainly by means of angiography. Sites of action were the tumour mass proper and the blood supply zones. In some cases, partial removal of the tumour was carried out in the usual way before or after cryodestruction. There are 3 kinds of further development after cryodestruction: regression, slow progression and rapid progression. Progression was found in 14 patients; 9 patients died within 2 weeks after the operation. In their cases, cryodestruction was by far insufficient. Dedifferentiated astrocytomas showed more a regressive behaviour than multiform glioblastomas. The possibility of local chemotherapy was also utilised."}
{"id": "PMID:204133", "title": "[Indicators of immunity in children vaccinated with live poliomyelitis vaccine].", "content": "Serological examination of 1057 children, residents of Leningrad, vaccinated with poliomyelitis vaccine at the appropriate calendar dates according to the scheme, showed the presence of antibodies to the polioviruses in 81.5-99.1% of the cases. There were more serologically negative children against the virus type III, and much less--against the virus type II. The value of the mean geometrical titres somewhat decreased with the advance of the children's age and the time lapse after the vaccination and revaccination. The greatest antibody titres determined were against the poliovirus type II, and the least--against type III. No antibodies against the viruses of types I and III were revealed in case of deficiency against the poliovirus type II. The number of children with the absence of antibodies against the poliovirus of all the types was insignificant.", "contents": "[Indicators of immunity in children vaccinated with live poliomyelitis vaccine]. Serological examination of 1057 children, residents of Leningrad, vaccinated with poliomyelitis vaccine at the appropriate calendar dates according to the scheme, showed the presence of antibodies to the polioviruses in 81.5-99.1% of the cases. There were more serologically negative children against the virus type III, and much less--against the virus type II. The value of the mean geometrical titres somewhat decreased with the advance of the children's age and the time lapse after the vaccination and revaccination. The greatest antibody titres determined were against the poliovirus type II, and the least--against type III. No antibodies against the viruses of types I and III were revealed in case of deficiency against the poliovirus type II. The number of children with the absence of antibodies against the poliovirus of all the types was insignificant."}
{"id": "PMID:204135", "title": "[Experimental study of combined staphylococcal, streptococcal and adenovirus infections in tissue culture].", "content": "Associated adenoviral, staphylococcus, and streptococcus infection was studied in the cultures of cells HEp-2 and PAO. Under conditions of monoinfection the cell culture largely inhibited the reproduction of staphylococci, and failed to influence the streptococci. In double and triple associated infections staphylococci overcame the inhibitory action of the cell culture. The pathogenic properties of cocci (plasma coagulation, hemotoxic properties) grown in the cell culture both under conditions of monoinfection, and in associations, failed to change. In double and triple associated infections adenoviruses did reproduce, but in lower titre than in monoinfection. Under conditions of mixed infection cocci penetrated and reproduced in the cell cytoplasm more intensively than in monoinfection. The cytopathic action was determined by viral associate, and was identical by its character to adenoviral monoinfection. A statistically significant increase in the activity of aldolase and transaminase enzymes was noted in mixed infection. The changes in the enzyme activity proved to depend on the character of the associations studied.", "contents": "[Experimental study of combined staphylococcal, streptococcal and adenovirus infections in tissue culture]. Associated adenoviral, staphylococcus, and streptococcus infection was studied in the cultures of cells HEp-2 and PAO. Under conditions of monoinfection the cell culture largely inhibited the reproduction of staphylococci, and failed to influence the streptococci. In double and triple associated infections staphylococci overcame the inhibitory action of the cell culture. The pathogenic properties of cocci (plasma coagulation, hemotoxic properties) grown in the cell culture both under conditions of monoinfection, and in associations, failed to change. In double and triple associated infections adenoviruses did reproduce, but in lower titre than in monoinfection. Under conditions of mixed infection cocci penetrated and reproduced in the cell cytoplasm more intensively than in monoinfection. The cytopathic action was determined by viral associate, and was identical by its character to adenoviral monoinfection. A statistically significant increase in the activity of aldolase and transaminase enzymes was noted in mixed infection. The changes in the enzyme activity proved to depend on the character of the associations studied."}
{"id": "PMID:204137", "title": "The effect of cyclic AMP on the maturation and degranulation of mast cells.", "content": "In short-term tissue cultures dibutyryl cAMP inhibits the cortisone-induced degranulation of mast cells. The effect of methylxanthine was found to be similar but developed at a slower rate. The increase of cAMP level also affected the maturation of mast cells, as the ratio of cells of mixed granulation increased, compared to the alcian blue- and safranin-present model inhibited degranulation.", "contents": "The effect of cyclic AMP on the maturation and degranulation of mast cells. In short-term tissue cultures dibutyryl cAMP inhibits the cortisone-induced degranulation of mast cells. The effect of methylxanthine was found to be similar but developed at a slower rate. The increase of cAMP level also affected the maturation of mast cells, as the ratio of cells of mixed granulation increased, compared to the alcian blue- and safranin-present model inhibited degranulation."}
{"id": "PMID:204139", "title": "Absence of positive feedback effect of oestrogen on LH release in patients with testicular feminization syndrome.", "content": "The response of serum LH to exogenous oestrogen administration was studied in 5 patients with testicular feminization syndrome (TFS). The serum LH levels were elevated in all the patients, while serum testosterone levels were within the normal male range. Serum FSH levels were elevated in 4 patients and normal in one patient. Intravenous administration of 100 microgram of LH-RH provoked a further increase in both LH and FSH. Following intravenous injection of 20 mg of conjugated oestrogen (Premarin), the LH levels were serially determined until 120 h in TFS patients, 5 normal males, and 10 normal females during the mid-follocular phase (D7-9). Both TFS patients and normal males showed no LH release following oestrogen injection in contrast to normal females who displayed a significant increase in LH with a peak at 48 to 56 h after the injection. These results seem to suggest that the insensitivity of the hypothalamus to androgen in TFS patients do not affect the sex differentiation of the hypothalamus. The possible role of oestradiol conversion from testosterone in the hypothalamus is discussed.", "contents": "Absence of positive feedback effect of oestrogen on LH release in patients with testicular feminization syndrome. The response of serum LH to exogenous oestrogen administration was studied in 5 patients with testicular feminization syndrome (TFS). The serum LH levels were elevated in all the patients, while serum testosterone levels were within the normal male range. Serum FSH levels were elevated in 4 patients and normal in one patient. Intravenous administration of 100 microgram of LH-RH provoked a further increase in both LH and FSH. Following intravenous injection of 20 mg of conjugated oestrogen (Premarin), the LH levels were serially determined until 120 h in TFS patients, 5 normal males, and 10 normal females during the mid-follocular phase (D7-9). Both TFS patients and normal males showed no LH release following oestrogen injection in contrast to normal females who displayed a significant increase in LH with a peak at 48 to 56 h after the injection. These results seem to suggest that the insensitivity of the hypothalamus to androgen in TFS patients do not affect the sex differentiation of the hypothalamus. The possible role of oestradiol conversion from testosterone in the hypothalamus is discussed."}
{"id": "PMID:204140", "title": "The effect of cyproterone acetate on the pituitary-adrenal axis in hirsute women.", "content": "The functioning of the hypothalamo-pituitary-adrenal axis was assessed in 10 adult women with idiopathic hirsutism treated for 2 weeks with the anti-androgen cyproterone acetate in a dose of 50 mg b. d. daily and in 4 patients treated for at least 3 months. Basal plasma ACTH and cortisol levels and the cortisol response to 8 h ACTH infusion were comparable before and during short-term treatment. The plasma ACTH and cortisol responses to insulin induced hypoglycaemia before and during anti-androgen therapy also were of the same order of magnitude. In the 4 patients treated for at least 3 months also no suppressive effect of the anti-androgen on basal plasma cortisol levels was observed. From these data the conclusion seems warranted that short-term cyproterone acetate treatment in the given dose not significantly influences pituitary-adrenal function in adult women with idiopathic hirsutism.", "contents": "The effect of cyproterone acetate on the pituitary-adrenal axis in hirsute women. The functioning of the hypothalamo-pituitary-adrenal axis was assessed in 10 adult women with idiopathic hirsutism treated for 2 weeks with the anti-androgen cyproterone acetate in a dose of 50 mg b. d. daily and in 4 patients treated for at least 3 months. Basal plasma ACTH and cortisol levels and the cortisol response to 8 h ACTH infusion were comparable before and during short-term treatment. The plasma ACTH and cortisol responses to insulin induced hypoglycaemia before and during anti-androgen therapy also were of the same order of magnitude. In the 4 patients treated for at least 3 months also no suppressive effect of the anti-androgen on basal plasma cortisol levels was observed. From these data the conclusion seems warranted that short-term cyproterone acetate treatment in the given dose not significantly influences pituitary-adrenal function in adult women with idiopathic hirsutism."}
{"id": "PMID:204142", "title": "Suprahypophyseal dysfunction in a patient with asexual ateleiosis.", "content": "The neuroendocrine function of a 19 years old female dwarf with primary amenorrhoea and lack of sexual development (asexual ateleiosis) was studied. Undetectable fasting plasma levels of growth hormone (GH) and a lack of response to three different provocative stimuli was observed. Oestrogen administratin did not modify the GH response. Thyroid and adrenal function were within normal limits. Undetectable plasma levels of immunoreactive oestradiol and lack of oestrogenic activity in vaginal smears indicated absence of ovarian function. Low levels of circulating gonadotrophins with a significant rise after synthetic LH-RH administration was demonstrated, while clomiphene citrate failed to induce ovulation. Following 6 months of continuous GH administration a significant increase in the growth rate was evident, whereas no pubertal development was observed. These data are interpreted as demonstrating the suprahypophyseal origin of the sexual infantilism in a patient with inappropriate GH secretion. It is suggested that a combined deficiency of LH-RH and GH-RH may account for the aetiology of this disorder.", "contents": "Suprahypophyseal dysfunction in a patient with asexual ateleiosis. The neuroendocrine function of a 19 years old female dwarf with primary amenorrhoea and lack of sexual development (asexual ateleiosis) was studied. Undetectable fasting plasma levels of growth hormone (GH) and a lack of response to three different provocative stimuli was observed. Oestrogen administratin did not modify the GH response. Thyroid and adrenal function were within normal limits. Undetectable plasma levels of immunoreactive oestradiol and lack of oestrogenic activity in vaginal smears indicated absence of ovarian function. Low levels of circulating gonadotrophins with a significant rise after synthetic LH-RH administration was demonstrated, while clomiphene citrate failed to induce ovulation. Following 6 months of continuous GH administration a significant increase in the growth rate was evident, whereas no pubertal development was observed. These data are interpreted as demonstrating the suprahypophyseal origin of the sexual infantilism in a patient with inappropriate GH secretion. It is suggested that a combined deficiency of LH-RH and GH-RH may account for the aetiology of this disorder."}
{"id": "PMID:204138", "title": "Fasting plasma cyclic AMP levels in an adult diabetic and non-diabetic group.", "content": "Fasting plasma cyclic adenosine monophosphate (cAMP) was measured in 50 mature-onset diabetic patients and in 111 non-diabetic patients. Methods used to determine plasma cAMP are described. The addition of sepharose agar beads to the bovine adrenocortical binding protein has considerably improved the sensitivity and simplified the radioligand-receptor assay of cAMP. No statistical differences in plasma cAMP were noted in relation to sex in either group, to the presence of diabetes mellitus or to age or weight in the non-diabetic patients. Plasma cGMP levels are now being studied to determine if these may prove better indicators of insulin activity than plasma cAMP.", "contents": "Fasting plasma cyclic AMP levels in an adult diabetic and non-diabetic group. Fasting plasma cyclic adenosine monophosphate (cAMP) was measured in 50 mature-onset diabetic patients and in 111 non-diabetic patients. Methods used to determine plasma cAMP are described. The addition of sepharose agar beads to the bovine adrenocortical binding protein has considerably improved the sensitivity and simplified the radioligand-receptor assay of cAMP. No statistical differences in plasma cAMP were noted in relation to sex in either group, to the presence of diabetes mellitus or to age or weight in the non-diabetic patients. Plasma cGMP levels are now being studied to determine if these may prove better indicators of insulin activity than plasma cAMP."}
{"id": "PMID:204147", "title": "[Histotopic of glycosidases in the oviduct of the quail (Coturnix coturnix japonica) (author's transl)].", "content": "The activities of 6 glycosidases (n-acetyl-beta-glucosaminidase, beta-galactosidase, beta-glucuronidase, alpha-galactosidase, alpha-fucosidase and alpha-mannosidase) in the oviduct of the quail (Coturnix coturnix japonica) were studied with histochemical methods. Alpha-galactosidase and alpha-fucosidase showed a weak to moderate activity in the surface epithelium and in most of the glands of the oviduct. A Distinct reactivity of beta-glucuronidase was observed in the surface epithelium of the whole oviduct and in the glands of the uterovaginal-region. A moderate to distinct reactivity of n-acetyl-beta-glucosaminidase cound be demonstrated in the epithelium and in the glands of all regions of the oviduct. The comparatively highest activity of this enzyme was found in the glands of the magnum and in the surface epithelium of the uterus. The possible functions of the glycosidases in the oviduct are discussed briefly.", "contents": "[Histotopic of glycosidases in the oviduct of the quail (Coturnix coturnix japonica) (author's transl)]. The activities of 6 glycosidases (n-acetyl-beta-glucosaminidase, beta-galactosidase, beta-glucuronidase, alpha-galactosidase, alpha-fucosidase and alpha-mannosidase) in the oviduct of the quail (Coturnix coturnix japonica) were studied with histochemical methods. Alpha-galactosidase and alpha-fucosidase showed a weak to moderate activity in the surface epithelium and in most of the glands of the oviduct. A Distinct reactivity of beta-glucuronidase was observed in the surface epithelium of the whole oviduct and in the glands of the uterovaginal-region. A moderate to distinct reactivity of n-acetyl-beta-glucosaminidase cound be demonstrated in the epithelium and in the glands of all regions of the oviduct. The comparatively highest activity of this enzyme was found in the glands of the magnum and in the surface epithelium of the uterus. The possible functions of the glycosidases in the oviduct are discussed briefly."}
{"id": "PMID:204148", "title": "The vibration perception threshold in gastrectomized patients with low serum B12. A clinical and biothesiometric follow-up after intensive B12 therapy.", "content": "In 42 gastrectomized patients with low serum B12 the vibration perception threshold (VPT) was significantly elevated as compared with a control group. Forty patients were followed up after 6-12 months of intensive vitamin B12 therapy. Within an adequately treated group (25 patients) remission of symptoms and signs of peripheral neuropathy was observed, including a statistically significant reduction of the VPT measured on the medial malleolus and big toe. Such a reduction was not observed in the adequately treated group of patients with myclopathy. Findings in the inadequately treated group were less definite, both as regards remission of clinical findings and VPT. In four untreated patients the neurological symptoms and signs progressed during the follow-up period. On the basis of these findings intensive and long-lasting treatment with vitamin B12 is recommended for gastrectomized patients showing signs of neuropathy.", "contents": "The vibration perception threshold in gastrectomized patients with low serum B12. A clinical and biothesiometric follow-up after intensive B12 therapy. In 42 gastrectomized patients with low serum B12 the vibration perception threshold (VPT) was significantly elevated as compared with a control group. Forty patients were followed up after 6-12 months of intensive vitamin B12 therapy. Within an adequately treated group (25 patients) remission of symptoms and signs of peripheral neuropathy was observed, including a statistically significant reduction of the VPT measured on the medial malleolus and big toe. Such a reduction was not observed in the adequately treated group of patients with myclopathy. Findings in the inadequately treated group were less definite, both as regards remission of clinical findings and VPT. In four untreated patients the neurological symptoms and signs progressed during the follow-up period. On the basis of these findings intensive and long-lasting treatment with vitamin B12 is recommended for gastrectomized patients showing signs of neuropathy."}
{"id": "PMID:204151", "title": "Efficacy of zoster immunoglobulin in prophylaxis of varicella in high-risk patients.", "content": "During a period of 2 1/2 years 190 children have been prophylactically treated with zoster immunoglobulin in norway. Information on 130 (68%) of these children was obtained. This group included patients suffering from leukemia, lymphoma, and other malignant disorders, and patients with autoimmune diseases, with impaired immune mechanisms or with for other reasons increased frequency of infections, as well as premature and weak newborns, and infants born to mothers who developed varicella during the last 4 days before delivery. Of the patients who received zoster immunoglobulin within 3 days after exposure, 2.9% developed weak symptoms of varicella. When zoster immunoglobulin was administered 4-5 days after exposure, 37.5% contracted varicella, and when given more than 5 days after exposure, 50% developed the disease. The 9 neonates with possible intrauterine exposure are not included in these figures.", "contents": "Efficacy of zoster immunoglobulin in prophylaxis of varicella in high-risk patients. During a period of 2 1/2 years 190 children have been prophylactically treated with zoster immunoglobulin in norway. Information on 130 (68%) of these children was obtained. This group included patients suffering from leukemia, lymphoma, and other malignant disorders, and patients with autoimmune diseases, with impaired immune mechanisms or with for other reasons increased frequency of infections, as well as premature and weak newborns, and infants born to mothers who developed varicella during the last 4 days before delivery. Of the patients who received zoster immunoglobulin within 3 days after exposure, 2.9% developed weak symptoms of varicella. When zoster immunoglobulin was administered 4-5 days after exposure, 37.5% contracted varicella, and when given more than 5 days after exposure, 50% developed the disease. The 9 neonates with possible intrauterine exposure are not included in these figures."}
{"id": "PMID:204152", "title": "Studies on a patient with in vivo evidence of type I glycogenosis and normal enzyme activities in vitro.", "content": "Biochemical and clinical studies on a patient with hepatic glycogen storage disease are reported. The patient showed many of the clinical and biochemical features of type I glycogenosis (glucose-6-phosphatase deficiency), but had normal activities of the following enzymes in liver tissue: glucose-6-phosphatase (EC3.1.3.9); amylo-1,6-glucosidase (EC3.2.1.33); glycogen phosphorylase (EC2.4.1.1); fructose-1,6-diphosphatase (EC3.1.3.11). The urinary excretion of 2-oxoglutaric acid was greatly increased in this patient and in a case of enzymologically proven type I glycogenosis. Abnormal 2-oxoglutaric aciduria has not been previously reported in the glycogen storage diseases. The results are discussed in relation to the possible nature of the underlying biochemical defect in patients of this type.", "contents": "Studies on a patient with in vivo evidence of type I glycogenosis and normal enzyme activities in vitro. Biochemical and clinical studies on a patient with hepatic glycogen storage disease are reported. The patient showed many of the clinical and biochemical features of type I glycogenosis (glucose-6-phosphatase deficiency), but had normal activities of the following enzymes in liver tissue: glucose-6-phosphatase (EC3.1.3.9); amylo-1,6-glucosidase (EC3.2.1.33); glycogen phosphorylase (EC2.4.1.1); fructose-1,6-diphosphatase (EC3.1.3.11). The urinary excretion of 2-oxoglutaric acid was greatly increased in this patient and in a case of enzymologically proven type I glycogenosis. Abnormal 2-oxoglutaric aciduria has not been previously reported in the glycogen storage diseases. The results are discussed in relation to the possible nature of the underlying biochemical defect in patients of this type."}
{"id": "PMID:204153", "title": "Differentiation of the fetal adrenal cortex of rats--its experimental observation in vivo.", "content": "The development and tissue differentiation of the adrenal cortex of rats were studied by giving experimental treatments to the fetus in vivo. A low-ACTH-condition was given to the fetus by administrating Dexamethasone through its mother, or directly into the subcutaneous tissue of the fetus, or by decapitation, brain aspiration or hypophysectomy. When the fetus was given the low-ACTH-condition for the last 5 days or more, the hypoplastic adrenal cortex developed specifically. It had nearly normal zona glomerulosa (ZG), and poorly differentiated zona fasciculo-reticularis (ZF-R) without differentiated ZF-R. The observing day was settled at 21 1/2 days old. The shorter the period of low-ACTH-condition was, the more thickened the differentiated zone (ZF-R) grew. On the contrary, the poorly differentiated layer became thinner in proportion to the period of low-ACTH-condition. The poorly differentiated cortical cell had ACTH-reactivity. It seems that the development and tissue differentiation of the ZF-R depend on fetal own ACTH, and poorly differentiated cortical cells appear below the ZG, and differentiate by ACTH and were gradually pushed inside. The zona glomerulosa develops and differentiates without dependence of ACTH.", "contents": "Differentiation of the fetal adrenal cortex of rats--its experimental observation in vivo. The development and tissue differentiation of the adrenal cortex of rats were studied by giving experimental treatments to the fetus in vivo. A low-ACTH-condition was given to the fetus by administrating Dexamethasone through its mother, or directly into the subcutaneous tissue of the fetus, or by decapitation, brain aspiration or hypophysectomy. When the fetus was given the low-ACTH-condition for the last 5 days or more, the hypoplastic adrenal cortex developed specifically. It had nearly normal zona glomerulosa (ZG), and poorly differentiated zona fasciculo-reticularis (ZF-R) without differentiated ZF-R. The observing day was settled at 21 1/2 days old. The shorter the period of low-ACTH-condition was, the more thickened the differentiated zone (ZF-R) grew. On the contrary, the poorly differentiated layer became thinner in proportion to the period of low-ACTH-condition. The poorly differentiated cortical cell had ACTH-reactivity. It seems that the development and tissue differentiation of the ZF-R depend on fetal own ACTH, and poorly differentiated cortical cells appear below the ZG, and differentiate by ACTH and were gradually pushed inside. The zona glomerulosa develops and differentiates without dependence of ACTH."}
{"id": "PMID:204154", "title": "Transmission and scanning electron microscopic observations of mouse adrenocortical adenoma cells (Y-1) in non-stimulated and stimulated states.", "content": "ACTH sensitive murine adrenocortical adenoma cells (Y-1) were examined by transmission and scanning electron microscopes under non-stimulated and stimulated conditions. They showed the ultrastructural characteristics which were fairly different from those of the original adrenocortical cells of LAF1 mice. The smooth-surfaced endoplasmic reticulum (sER) were poorly developed, and the mitochondrial cristae showed lamellar rather than tubular or tubulo-vesicular type. Administration of ACTH induced rounding-up of the Y-1 cells with slight increase in sER, BUt no mitochondria with vesicular inner structure appeared. The effects of dbcAMP on the morphology of the Y-1 cells were similar to those of ACTH except that the rounding-up occurred more rapidly and uniformly.", "contents": "Transmission and scanning electron microscopic observations of mouse adrenocortical adenoma cells (Y-1) in non-stimulated and stimulated states. ACTH sensitive murine adrenocortical adenoma cells (Y-1) were examined by transmission and scanning electron microscopes under non-stimulated and stimulated conditions. They showed the ultrastructural characteristics which were fairly different from those of the original adrenocortical cells of LAF1 mice. The smooth-surfaced endoplasmic reticulum (sER) were poorly developed, and the mitochondrial cristae showed lamellar rather than tubular or tubulo-vesicular type. Administration of ACTH induced rounding-up of the Y-1 cells with slight increase in sER, BUt no mitochondria with vesicular inner structure appeared. The effects of dbcAMP on the morphology of the Y-1 cells were similar to those of ACTH except that the rounding-up occurred more rapidly and uniformly."}
{"id": "PMID:204155", "title": "Correlation of alkaline phosphatase staining of cortisol-producing adrenocortical tumors with dexamethasone suppression and ACTH stimulation.", "content": "The histochemical activity of alkaline phosphatase (Al-Pase), the induction of which is one of the effects of ACTH on the adrenocortical cells, was examined in 10 adrenocortical tumors causing Cushing's syndrome and in 65 adrenal cortices. All of the compact cells in every gland, and almost all, about half, or a small proportion in the four tumors showed Al-Pase activity. These tumors decreased in steroidogenesis after the administration of dexamethasone. No compact cells exhibited the activity in six tumors, none of which was \"dexamethasone-suppressible\". Three of the seven attached glands examined were halfway between those of typical Cushing's syndrome and those of other than Cushing's syndrome from the viewpoint of compact/clear cell morphology. All of the tumors that had Al-Pase-positive clear cells increased in steroidogenesis after ACTH administration. These results suggested that Al-Pase activity of tumor cells was also ACTH effect and that a decrease in steroidogenesis of tumors after dexamethasone administration was due not to fluctuations but to suppression of intrinsic ACTH.", "contents": "Correlation of alkaline phosphatase staining of cortisol-producing adrenocortical tumors with dexamethasone suppression and ACTH stimulation. The histochemical activity of alkaline phosphatase (Al-Pase), the induction of which is one of the effects of ACTH on the adrenocortical cells, was examined in 10 adrenocortical tumors causing Cushing's syndrome and in 65 adrenal cortices. All of the compact cells in every gland, and almost all, about half, or a small proportion in the four tumors showed Al-Pase activity. These tumors decreased in steroidogenesis after the administration of dexamethasone. No compact cells exhibited the activity in six tumors, none of which was \"dexamethasone-suppressible\". Three of the seven attached glands examined were halfway between those of typical Cushing's syndrome and those of other than Cushing's syndrome from the viewpoint of compact/clear cell morphology. All of the tumors that had Al-Pase-positive clear cells increased in steroidogenesis after ACTH administration. These results suggested that Al-Pase activity of tumor cells was also ACTH effect and that a decrease in steroidogenesis of tumors after dexamethasone administration was due not to fluctuations but to suppression of intrinsic ACTH."}
{"id": "PMID:204156", "title": "Titration of herpes simplex virus antibodies in human sera by the enzyme-linked immunosorbent assay (ELISA).", "content": "100 sera from healthy adults were titrated simultaneously for herpes simplex virus (HSV) antibodies by ELISA and neutralization. The ELISA was performed on microtitre plates where approximately 100 ng of detergent solubilized and chromatographically purified HSV glycoproteins was bound covalently to the plastic bottom of each well. The optical density (OD) values obtained by the use of the peroxidase-1.2phenylendiamindihydrochloride system showed good correlation with the neuratlizing antibody titres. Sera with very low neutralizing titres were clearly positive in ELISA.", "contents": "Titration of herpes simplex virus antibodies in human sera by the enzyme-linked immunosorbent assay (ELISA). 100 sera from healthy adults were titrated simultaneously for herpes simplex virus (HSV) antibodies by ELISA and neutralization. The ELISA was performed on microtitre plates where approximately 100 ng of detergent solubilized and chromatographically purified HSV glycoproteins was bound covalently to the plastic bottom of each well. The optical density (OD) values obtained by the use of the peroxidase-1.2phenylendiamindihydrochloride system showed good correlation with the neuratlizing antibody titres. Sera with very low neutralizing titres were clearly positive in ELISA."}
{"id": "PMID:204157", "title": "Effect of human leucocyte migration inhibitory factor (LIF) on 3', 5'-cyclic AMP levels of peripheral blood leucocytes.", "content": "The possible involvement of 3', 5'-cyclic AMP (cyclic AMP) in the mechanism of action of leucocyte migration inhbitory factory (LIF) was tested. LIF-treated human peripheral blood leucocytes were incubated at 37 degrees C for various times between 0 and 22 h. The concentrations of cyclic AMP in these cultures did not differ from those in controls. Furthermore, LIF did not affect the cellular release of cyclic AMP. Neither when testing purified neutrophils, which are the prime targets of LIF action, an effect of LIF was found. Cyclic AMP levels decreased with time of incubation, whether testing mononuclear cells (92 per cent lymphocytes), purified neutrophils (98 per cent), or buffy coat cells (72 per cent neutrophils; 22 per cent lymphocytes). However, a transient and as yet unexplained increase in the cyclic AMP levels of the latter mixed population of cells was manifested within 10 to 30 min of incubation.", "contents": "Effect of human leucocyte migration inhibitory factor (LIF) on 3', 5'-cyclic AMP levels of peripheral blood leucocytes. The possible involvement of 3', 5'-cyclic AMP (cyclic AMP) in the mechanism of action of leucocyte migration inhbitory factory (LIF) was tested. LIF-treated human peripheral blood leucocytes were incubated at 37 degrees C for various times between 0 and 22 h. The concentrations of cyclic AMP in these cultures did not differ from those in controls. Furthermore, LIF did not affect the cellular release of cyclic AMP. Neither when testing purified neutrophils, which are the prime targets of LIF action, an effect of LIF was found. Cyclic AMP levels decreased with time of incubation, whether testing mononuclear cells (92 per cent lymphocytes), purified neutrophils (98 per cent), or buffy coat cells (72 per cent neutrophils; 22 per cent lymphocytes). However, a transient and as yet unexplained increase in the cyclic AMP levels of the latter mixed population of cells was manifested within 10 to 30 min of incubation."}
{"id": "PMID:204158", "title": "Cadmium feeding: apparent depression of atrioventricular-his-Purkinje conduction system.", "content": "Male rats were exposed to 0, 10 and 130 p.p.m. cadmium administered in 0.5% saline drinking water for 71 days. Biweekly records of ECGs, Hct, body weight and blood levels of cadmium were made. Rats exposed to 130 p.p.m. cadmium showed slower growth rates and declining Hct indicative of acute cadmium poisoning. At the end of the experimental period, carotid artery blood pressures and whole heart cadmium levels were determined. Although no significant blood pressure changes were observed in the experimental groups, the cadmium content of the hearts of the higher dose group was significantly higher than in the hearts of the lower dose group. The PR interval of the ECG was lengthened progressively and to the same extent in both experimental groups with continued cadmium feeding. These experiments offer evidence that the accumulation of even moderate amounts of cadmium will be manifested in marked changes in cardiac conduction without overt signs of cadmium poisoning.", "contents": "Cadmium feeding: apparent depression of atrioventricular-his-Purkinje conduction system. Male rats were exposed to 0, 10 and 130 p.p.m. cadmium administered in 0.5% saline drinking water for 71 days. Biweekly records of ECGs, Hct, body weight and blood levels of cadmium were made. Rats exposed to 130 p.p.m. cadmium showed slower growth rates and declining Hct indicative of acute cadmium poisoning. At the end of the experimental period, carotid artery blood pressures and whole heart cadmium levels were determined. Although no significant blood pressure changes were observed in the experimental groups, the cadmium content of the hearts of the higher dose group was significantly higher than in the hearts of the lower dose group. The PR interval of the ECG was lengthened progressively and to the same extent in both experimental groups with continued cadmium feeding. These experiments offer evidence that the accumulation of even moderate amounts of cadmium will be manifested in marked changes in cardiac conduction without overt signs of cadmium poisoning."}
{"id": "PMID:204161", "title": "The effect of smoking on selected coronary heart disease risk factors in middle-aged men.", "content": "Associations between smoking and selected factors supposed to promote coronary heart disease (CHD) were studied in 1832 healthy men, 809 of whom were smokers. Triglycerides were 7% higher in smokers; the heaviest smokers had the highest levels. Unfavourable changes were not seen in the other parameters in smokers. There was no trend indicating an influence of smoking on total and HDL cholesterol in the individuals who had abstained from smoking for a few hours just before the examination. Body mass index and weight, blood pressure and resting heart rate were lower in smokers, whereas heart volume, glucose tolerance, thyroid function and ECG findings did not differ significantly in smokers and non-smokers. The present study indicates that smoking promotes the development of CHD independently of the commonly accepted CHD risk factors.", "contents": "The effect of smoking on selected coronary heart disease risk factors in middle-aged men. Associations between smoking and selected factors supposed to promote coronary heart disease (CHD) were studied in 1832 healthy men, 809 of whom were smokers. Triglycerides were 7% higher in smokers; the heaviest smokers had the highest levels. Unfavourable changes were not seen in the other parameters in smokers. There was no trend indicating an influence of smoking on total and HDL cholesterol in the individuals who had abstained from smoking for a few hours just before the examination. Body mass index and weight, blood pressure and resting heart rate were lower in smokers, whereas heart volume, glucose tolerance, thyroid function and ECG findings did not differ significantly in smokers and non-smokers. The present study indicates that smoking promotes the development of CHD independently of the commonly accepted CHD risk factors."}
{"id": "PMID:204177", "title": "The tropical amblyopia syndrome (or tropical nutritional amblyopia) in the Mid-Western State of Nigeria.", "content": "One hundred and seven patients from the Mid-Western State of Nigeria with the tropical amblyopia syndrome are reported. Ninety-five patients (88.8%) had the amblyopia syndrome mainly; twelve patients (11.2%) had amblyopia and other manifestations of the tropical ataxic neuropathy. The young, aged 10-20 years, represented by sixty-six patients (61.8%), are predominantly affected by the uncomplicated syndrome. Thirteen patients (12.1%) showed muco-cutaneous evidence of avitaminosis. Fifty patients (46.7%) had temporal pallor of the optic discs, bilaterally, another fifty (46.7%) had normal discs, two (2.8%) showed pink discs. Generalized field constriction is the common field defect, though central or centro-caecal scotoma can occur. Red/green defect was present in seven patients. It is a disease of the poor or those living on a basic monotonous diet consisting mainly of cassava (mannihot) and its derivatives. It is a significant cause of defective vision in Mid-Western Nigeria.", "contents": "The tropical amblyopia syndrome (or tropical nutritional amblyopia) in the Mid-Western State of Nigeria. One hundred and seven patients from the Mid-Western State of Nigeria with the tropical amblyopia syndrome are reported. Ninety-five patients (88.8%) had the amblyopia syndrome mainly; twelve patients (11.2%) had amblyopia and other manifestations of the tropical ataxic neuropathy. The young, aged 10-20 years, represented by sixty-six patients (61.8%), are predominantly affected by the uncomplicated syndrome. Thirteen patients (12.1%) showed muco-cutaneous evidence of avitaminosis. Fifty patients (46.7%) had temporal pallor of the optic discs, bilaterally, another fifty (46.7%) had normal discs, two (2.8%) showed pink discs. Generalized field constriction is the common field defect, though central or centro-caecal scotoma can occur. Red/green defect was present in seven patients. It is a disease of the poor or those living on a basic monotonous diet consisting mainly of cassava (mannihot) and its derivatives. It is a significant cause of defective vision in Mid-Western Nigeria."}
{"id": "PMID:204178", "title": "Herpes type-2 virus antibody status in groups of patients with neoplasm in Ibadan.", "content": "Various studies have associated Herpes Type-2 (HT-2) virus with carcinoma of the cervix, especially the squamous cell type. In the present study, prevalence of HT-2 virus antibodies was found to be significantly higher in patients with squamous cell carcinoma of the cervix than in cases with squamous cell carcinoma of sites other than the cervix, and other pelvic and extrapelvic malignancies (P less than 0.001). It was concluded that no association could be found between Herpes Type-2 virus and malignancies of sites other than the cervix.", "contents": "Herpes type-2 virus antibody status in groups of patients with neoplasm in Ibadan. Various studies have associated Herpes Type-2 (HT-2) virus with carcinoma of the cervix, especially the squamous cell type. In the present study, prevalence of HT-2 virus antibodies was found to be significantly higher in patients with squamous cell carcinoma of the cervix than in cases with squamous cell carcinoma of sites other than the cervix, and other pelvic and extrapelvic malignancies (P less than 0.001). It was concluded that no association could be found between Herpes Type-2 virus and malignancies of sites other than the cervix."}
{"id": "PMID:204180", "title": "An evaluation of the GCA respirable dust monitor 101-1.", "content": "The GCA RDM 101-1 has been evaluated using aerosols of coal, Arizona road dust, silica, potash, and rock (copper ore) particles. The effects of the dust mass concentration, particle size distribution, and dust material on the instrument response were investigated. The instrument was found to measure the mass concentrations of respirable dust aerosols up to about 16 mg/m3 for coal and rock dust and about 20 mg/m3 for silica, potash, and Arizona road dust, providing there is not appreciable mass in the size range below approximateley 0.7 micrometer aerodynamic diameter.", "contents": "An evaluation of the GCA respirable dust monitor 101-1. The GCA RDM 101-1 has been evaluated using aerosols of coal, Arizona road dust, silica, potash, and rock (copper ore) particles. The effects of the dust mass concentration, particle size distribution, and dust material on the instrument response were investigated. The instrument was found to measure the mass concentrations of respirable dust aerosols up to about 16 mg/m3 for coal and rock dust and about 20 mg/m3 for silica, potash, and Arizona road dust, providing there is not appreciable mass in the size range below approximateley 0.7 micrometer aerodynamic diameter."}
{"id": "PMID:204181", "title": "A dust generator for laboratory use.", "content": "A dust generator has been developed to produce dry dust from powderous materials for instrument calibration and laboratory studies. The powder is fed at a constant rate via a chain conveyor into a fluidized bed where the particles are deagglomerated and aerosolized. The powder feed rate is raviable from 1.2 to 36 mm3/min and the air flow rate from 9 to 30 Lpm. Aerosols of coal, silica, potash, rock, and Arizona road dust have been successfully generated for calibrating optical particle counters and aerosol mass monitors.", "contents": "A dust generator for laboratory use. A dust generator has been developed to produce dry dust from powderous materials for instrument calibration and laboratory studies. The powder is fed at a constant rate via a chain conveyor into a fluidized bed where the particles are deagglomerated and aerosolized. The powder feed rate is raviable from 1.2 to 36 mm3/min and the air flow rate from 9 to 30 Lpm. Aerosols of coal, silica, potash, rock, and Arizona road dust have been successfully generated for calibrating optical particle counters and aerosol mass monitors."}
{"id": "PMID:204183", "title": "Management of hypercholesterolemia: evaluation of practical clinical approaches in healthy young adults.", "content": "A work site-located clinic screened 6,000 employees (91 percent participation) and identified 146 hypercholesterolemic subjects (100 percent initial participation, 12 percent subsequent dropout rate). The subjects, aged 20 to 50 years, were randomly classified into four groups: Group A, treatment in a lipid intervention clinic with diet for 6 weeks, then diet plus clofibrate for the subsequent 18 weeks; Group B, diet treatment from a clinic nutritionist with the cooperation of the subject's private physician; Group C, referral for treatment by a private physician; and Group D, no intervention. Initial mean cholesterol was 294 mg/100 ml. At 24 weeks, all intervention groups had decreases in serum cholesterol (Group A, 12 percent; Group B, 15 percent; Group C, 17 percent; P less than 0.001). The control group (D) had a small decrease in cholesterol (4 percent). Decreases in cholesterol were correlated with weight loss and decrease in fasting serum triglycerides but not with the use of clofibrate. Serum cholesterol can be reduced in healthy young adults by several practical methods.", "contents": "Management of hypercholesterolemia: evaluation of practical clinical approaches in healthy young adults. A work site-located clinic screened 6,000 employees (91 percent participation) and identified 146 hypercholesterolemic subjects (100 percent initial participation, 12 percent subsequent dropout rate). The subjects, aged 20 to 50 years, were randomly classified into four groups: Group A, treatment in a lipid intervention clinic with diet for 6 weeks, then diet plus clofibrate for the subsequent 18 weeks; Group B, diet treatment from a clinic nutritionist with the cooperation of the subject's private physician; Group C, referral for treatment by a private physician; and Group D, no intervention. Initial mean cholesterol was 294 mg/100 ml. At 24 weeks, all intervention groups had decreases in serum cholesterol (Group A, 12 percent; Group B, 15 percent; Group C, 17 percent; P less than 0.001). The control group (D) had a small decrease in cholesterol (4 percent). Decreases in cholesterol were correlated with weight loss and decrease in fasting serum triglycerides but not with the use of clofibrate. Serum cholesterol can be reduced in healthy young adults by several practical methods."}
{"id": "PMID:204184", "title": "Malignant fibrous histiocytoma: an ultrastructural study of six cases.", "content": "The ultrastructures of six malignant fibrous histiocytomas were studied. The lesions were composed of different proportions of fibroblastic- and histiocytic-appearing cells. Intermediate, undifferentiated, and foam cells also were present. Three of the lesions had some \"fibroblasts\" that had intracytoplasmic bundles of filaments with focal densities (myofibroblastic cells). Malignant fibrous histiocytoma is considered a sarcoma that has an undifferentiated mesenchymal cell origin, that differentiates along a broad fibroblastic and histiocytic (fibrohistiocytic) spectrum, and that usually has a predominant \"fibroblastic\" component.", "contents": "Malignant fibrous histiocytoma: an ultrastructural study of six cases. The ultrastructures of six malignant fibrous histiocytomas were studied. The lesions were composed of different proportions of fibroblastic- and histiocytic-appearing cells. Intermediate, undifferentiated, and foam cells also were present. Three of the lesions had some \"fibroblasts\" that had intracytoplasmic bundles of filaments with focal densities (myofibroblastic cells). Malignant fibrous histiocytoma is considered a sarcoma that has an undifferentiated mesenchymal cell origin, that differentiates along a broad fibroblastic and histiocytic (fibrohistiocytic) spectrum, and that usually has a predominant \"fibroblastic\" component."}
{"id": "PMID:204193", "title": "Extracellular hydrolytic enzymes of rabbit dermal tuberculous lesions and tuberculin reactions collected in skin chambers.", "content": "To evaluate extracellular hydrolytic enzymes in an in vivo system, plastic chambers were glued over rabbit dermal BCG lesions in various stages of development, after the central epithelium was removed with a scalpel. They were filled with tissue culture medium and left in place 2 days. The following enzymes in the fluid were assayed: collagenase (an enzyme secreted but not stored in macrophages); lysozyme (both secreted and stored); DNase and RNase (released on cell death and possibly regurgitated but not secreted); and, as a control, lactic dehydrogenase (released only on cell death). Tissue sections were prepared and studied histologically for the type of cell infiltrate, for beta-galactosidase (our marker enzyme for macrophage activation), and for necrosis. At 11 and 18 days of age the BCG lesions were largest and the number of activated macrophages in the chamber beds was highest. At this time the levels of the five enzymes assayed in the chamber fluids reached their peaks, tuberculin hypersensitivity was well developed, and the bacilli components would still be plentiful. In general, the chamber fluids from 11- and 18-day BCG lesions contained higher enzyme levels than chamber fluids from tuberculin reactions. Active collagenase was only detected in fluids from such BCG lesions. Evidently, the serum in the chamber fluids was sufficient to inhibit the lower amounts of collagenase probably released from smaller BCG lesions and tuberculin reactions (and from the 2-week polystyrene lesions that were also evaluated). These studies demonstrate that in chronic inflammatory reactions, both acid-acting and neutral-acting hydrolytic enzymes are released extracellularly. Tissue components would be hydrolyzed locally wherever the acid-acting hydrolytic enzymes encounter a drop in pH and wherever the concentration of neutral-acting hydrolytic enzymes exceeds the concentration of their inhibitors.", "contents": "Extracellular hydrolytic enzymes of rabbit dermal tuberculous lesions and tuberculin reactions collected in skin chambers. To evaluate extracellular hydrolytic enzymes in an in vivo system, plastic chambers were glued over rabbit dermal BCG lesions in various stages of development, after the central epithelium was removed with a scalpel. They were filled with tissue culture medium and left in place 2 days. The following enzymes in the fluid were assayed: collagenase (an enzyme secreted but not stored in macrophages); lysozyme (both secreted and stored); DNase and RNase (released on cell death and possibly regurgitated but not secreted); and, as a control, lactic dehydrogenase (released only on cell death). Tissue sections were prepared and studied histologically for the type of cell infiltrate, for beta-galactosidase (our marker enzyme for macrophage activation), and for necrosis. At 11 and 18 days of age the BCG lesions were largest and the number of activated macrophages in the chamber beds was highest. At this time the levels of the five enzymes assayed in the chamber fluids reached their peaks, tuberculin hypersensitivity was well developed, and the bacilli components would still be plentiful. In general, the chamber fluids from 11- and 18-day BCG lesions contained higher enzyme levels than chamber fluids from tuberculin reactions. Active collagenase was only detected in fluids from such BCG lesions. Evidently, the serum in the chamber fluids was sufficient to inhibit the lower amounts of collagenase probably released from smaller BCG lesions and tuberculin reactions (and from the 2-week polystyrene lesions that were also evaluated). These studies demonstrate that in chronic inflammatory reactions, both acid-acting and neutral-acting hydrolytic enzymes are released extracellularly. Tissue components would be hydrolyzed locally wherever the acid-acting hydrolytic enzymes encounter a drop in pH and wherever the concentration of neutral-acting hydrolytic enzymes exceeds the concentration of their inhibitors."}
{"id": "PMID:204195", "title": "Energy relationships between cytosolic metabolism and mitochondrial respiration in rat heart.", "content": "Isolated rat heart was perfused with Langendorff's retrograde perfusion method, while the oxygen consumption and the left ventricular pressure were monitored continually. The steady-state contents of metabolites in the cardiac tissue, freeze clamped under various work-load conditions, were determined and the concentrations of free cytosolic ADP and AMP were calculated from the near equilibrium in creatine phosphokinase and adenylate kinase reactions. Increasing respiratory rate with increasing load was accompanied by a fall in the cytosolic free [ATP]/[ADP][Pi] but little change in the mitochondrial free [NAD+]/[NADH]. The free energy of ATP hydrolysis was calculated from the concentrations of the adenine nucleotides and compared with the values computed from the measured turnover number for cytochrome c and redox state of the mitochondrial NAD couple according to a mathematical model. The agreement between the two values was good over a wide range of metabolic conditions, which provides further support for the proposed near-equilibrium model of mitochondrial respiration with control exerted at the cytochrome oxidase-oxygen reaction.", "contents": "Energy relationships between cytosolic metabolism and mitochondrial respiration in rat heart. Isolated rat heart was perfused with Langendorff's retrograde perfusion method, while the oxygen consumption and the left ventricular pressure were monitored continually. The steady-state contents of metabolites in the cardiac tissue, freeze clamped under various work-load conditions, were determined and the concentrations of free cytosolic ADP and AMP were calculated from the near equilibrium in creatine phosphokinase and adenylate kinase reactions. Increasing respiratory rate with increasing load was accompanied by a fall in the cytosolic free [ATP]/[ADP][Pi] but little change in the mitochondrial free [NAD+]/[NADH]. The free energy of ATP hydrolysis was calculated from the concentrations of the adenine nucleotides and compared with the values computed from the measured turnover number for cytochrome c and redox state of the mitochondrial NAD couple according to a mathematical model. The agreement between the two values was good over a wide range of metabolic conditions, which provides further support for the proposed near-equilibrium model of mitochondrial respiration with control exerted at the cytochrome oxidase-oxygen reaction."}
{"id": "PMID:204196", "title": "Homeostatic regulation of cellular energy metabolism: experimental characterization in vivo and fit to a model.", "content": "Measurements in isolated liver cells, cultured kidney cells, protozoa (Tetrahymena pyriformis), and yeast (Candida utilis) indicate that homeostatic regulation of cellular energy metabolism is of common origin. In every case near equilibrium is maintained between the transfer of reducing equivalents from the intramitochondrial NAD couple to cytochrome c and the phosphorylation of cytosolic ADP to ATP. Under conditions of constant energy demand, changes in the intracellular phosphate concentration cause an adjustment in the [ATP]/[ADP] to maintain a constant [ATP]/[ADP][Pi] and constant respiratory rate. The regulation of mitochondrial respiration occurs as part of the reactions by which reduced cytochrome c is oxidized by molecular oxygen. At similar values for the [ATP]/[ADP][Pi] the respiratory rate increases with increasing reduction of cytochrome c. A model for mitochondrial respiratory control is found to give a good fit to the data in all of the different types of cells tested.", "contents": "Homeostatic regulation of cellular energy metabolism: experimental characterization in vivo and fit to a model. Measurements in isolated liver cells, cultured kidney cells, protozoa (Tetrahymena pyriformis), and yeast (Candida utilis) indicate that homeostatic regulation of cellular energy metabolism is of common origin. In every case near equilibrium is maintained between the transfer of reducing equivalents from the intramitochondrial NAD couple to cytochrome c and the phosphorylation of cytosolic ADP to ATP. Under conditions of constant energy demand, changes in the intracellular phosphate concentration cause an adjustment in the [ATP]/[ADP] to maintain a constant [ATP]/[ADP][Pi] and constant respiratory rate. The regulation of mitochondrial respiration occurs as part of the reactions by which reduced cytochrome c is oxidized by molecular oxygen. At similar values for the [ATP]/[ADP][Pi] the respiratory rate increases with increasing reduction of cytochrome c. A model for mitochondrial respiratory control is found to give a good fit to the data in all of the different types of cells tested."}
{"id": "PMID:204197", "title": "Intestinal contribution to secretion of very low density lipoproteins into plasma.", "content": "To resolve the question of the magnitude of the intestine's contribution to circulating very low density lipoproteins (VLDL), measurements of intestinal, hepatic, and total VLDL--triglyceride were made on the same animals or on animals studied under comparable conditions. Animals were examined in the fasted state and during infusion of a fat-free meal. Intestinal VLDL secretion was determined through timed collections of lymph from the mesenteric lymph duct; hepatic and total VLDL secretion rates were estimated by the accumulation of plasma VLDL after injections of Triton WR 1339. Results indicate that the intestine contributes only a minor portion (11%) of the amount of triglyceride entering into the plasma compartment in the fasted state. Although intestinal triglyceride production is increased by 50% (p less than 0.01) in fed rats, the overall contribution of the intestine is not significantly altered in fed rats and represents only 14--17% of total body VLDL secretion. Thus, although intestinal VLDL secretion can be modified experimentally, its total impact on endogenous triglyceride production in normotriglyceridemic rats is small.", "contents": "Intestinal contribution to secretion of very low density lipoproteins into plasma. To resolve the question of the magnitude of the intestine's contribution to circulating very low density lipoproteins (VLDL), measurements of intestinal, hepatic, and total VLDL--triglyceride were made on the same animals or on animals studied under comparable conditions. Animals were examined in the fasted state and during infusion of a fat-free meal. Intestinal VLDL secretion was determined through timed collections of lymph from the mesenteric lymph duct; hepatic and total VLDL secretion rates were estimated by the accumulation of plasma VLDL after injections of Triton WR 1339. Results indicate that the intestine contributes only a minor portion (11%) of the amount of triglyceride entering into the plasma compartment in the fasted state. Although intestinal triglyceride production is increased by 50% (p less than 0.01) in fed rats, the overall contribution of the intestine is not significantly altered in fed rats and represents only 14--17% of total body VLDL secretion. Thus, although intestinal VLDL secretion can be modified experimentally, its total impact on endogenous triglyceride production in normotriglyceridemic rats is small."}
{"id": "PMID:204199", "title": "Purification of distinct plasma membranes from canine renal medulla.", "content": "Two types of plasma membrane were purified from canine distal renal medulla by the techniques of differential and zonal density-gradient centrifugation followed by free-flow electrophoresis. One group of plasma membranes was identified as basal-laterally derived based on a 30-fold enrichment of Na-K-ATPase, a 20-fold enrichment of vasopressin-stimulated adenylate cyclase, and a 33-fold enrichment of [3H]vasopressin binding sites. The second type of plasma membrane was free of these markers, but had a cholesterol and phospholipid composition similar to them. Alkaline phosphatase also had a similar distribution in the two fractions. This lighter membrane fraction contained a membrane-bound cyclic AMP-dependent protein kinase as well as substrate for this kinase. In addition there was a 26-fold enrichment of specific activity of an anion (SO32-)-activated ATPase which was insensitive to mitochondrial ATPase inhibitor protein, in contrast to the mitochondrial fraction of the tissue. Based on the relative preponderance of collecting duct tissue in the distal medulla and the yield of membrane protein, these membranes are tentatively identified as containing apical membranes of the collecting duct.", "contents": "Purification of distinct plasma membranes from canine renal medulla. Two types of plasma membrane were purified from canine distal renal medulla by the techniques of differential and zonal density-gradient centrifugation followed by free-flow electrophoresis. One group of plasma membranes was identified as basal-laterally derived based on a 30-fold enrichment of Na-K-ATPase, a 20-fold enrichment of vasopressin-stimulated adenylate cyclase, and a 33-fold enrichment of [3H]vasopressin binding sites. The second type of plasma membrane was free of these markers, but had a cholesterol and phospholipid composition similar to them. Alkaline phosphatase also had a similar distribution in the two fractions. This lighter membrane fraction contained a membrane-bound cyclic AMP-dependent protein kinase as well as substrate for this kinase. In addition there was a 26-fold enrichment of specific activity of an anion (SO32-)-activated ATPase which was insensitive to mitochondrial ATPase inhibitor protein, in contrast to the mitochondrial fraction of the tissue. Based on the relative preponderance of collecting duct tissue in the distal medulla and the yield of membrane protein, these membranes are tentatively identified as containing apical membranes of the collecting duct."}
{"id": "PMID:204200", "title": "Potentiation of the cerebrovascular response to intra-arterial 5-hydroxytryptamine.", "content": "Infusion of 5-hydroxytryptamine (5HT) into the internal carotid artery of normal baboons was not accompanied by alteration of gray matter cerebral blood flow. In animals pretreated with depot estrogen and progesterone (dosage equivalent to oral contraceptive preparations), infusion of 5HT produced a marked decrease in gray matter blood flow. A similar decrease in flow was obtained when the 5HT was infused with a concentrate of beta-lipoprotein. Steroid substances appear to enhance the cerebrovascular constrictor responses to 5HT. A further series of six experiments has shown that the monoamine oxidase inhibitor tranylcypromine similarly produced constrictor responses to 5HT. It is possible that the steroids, the beta-lipoprotein, and the tranylcypromine produced constrictor responses to 5HT by the same mechanism (inhibition of cerebrovascular monoamine oxidase).", "contents": "Potentiation of the cerebrovascular response to intra-arterial 5-hydroxytryptamine. Infusion of 5-hydroxytryptamine (5HT) into the internal carotid artery of normal baboons was not accompanied by alteration of gray matter cerebral blood flow. In animals pretreated with depot estrogen and progesterone (dosage equivalent to oral contraceptive preparations), infusion of 5HT produced a marked decrease in gray matter blood flow. A similar decrease in flow was obtained when the 5HT was infused with a concentrate of beta-lipoprotein. Steroid substances appear to enhance the cerebrovascular constrictor responses to 5HT. A further series of six experiments has shown that the monoamine oxidase inhibitor tranylcypromine similarly produced constrictor responses to 5HT. It is possible that the steroids, the beta-lipoprotein, and the tranylcypromine produced constrictor responses to 5HT by the same mechanism (inhibition of cerebrovascular monoamine oxidase)."}
{"id": "PMID:204201", "title": "Fasting, adrenalectomy, and gluconeogenesis in the chicken and a carnivorous bird.", "content": "Previous studies showed that livers from carnivorous birds have a higher gluconeogenic capacity and higher levels of gluconeogenic enzymes than livers from granivorous birds. In this work we compare the effects of fasting and adrenalectomy on gluconeogenesis. Fasting in the chicken elicited increased rates of incorporation of 14C from alanine into blood glucose, increased gluconeogenesis in liver slices, and increased activities of four gluconeogenic enzymes: glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, alanine aminotransferase, and aspartate aminotransferase. These responses in the chicken resemble those observed in fasted rodents. In marked contrast, fasting in black vultures induced decreased rates of incorporation of alanine label into circulating glucose, decreased gluconeogenesis in liver slices, and no change in any of the four enzymes studied. This unusual response to fasting in the carnivorous bird is probably related to the high-protein-low-carbohydrate content of the diet. Fasted adrenalectomized birds (granivorous and carnivorous) had reduced rates of in vivo glucose synthesis, decreased liver gluconeogenesis, and lower activity of glucose-6-phosphatase and aspartate aminotransferase, without change in phosphoenolpyruvate carboxykinase and alanine aminotransferase activities.", "contents": "Fasting, adrenalectomy, and gluconeogenesis in the chicken and a carnivorous bird. Previous studies showed that livers from carnivorous birds have a higher gluconeogenic capacity and higher levels of gluconeogenic enzymes than livers from granivorous birds. In this work we compare the effects of fasting and adrenalectomy on gluconeogenesis. Fasting in the chicken elicited increased rates of incorporation of 14C from alanine into blood glucose, increased gluconeogenesis in liver slices, and increased activities of four gluconeogenic enzymes: glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, alanine aminotransferase, and aspartate aminotransferase. These responses in the chicken resemble those observed in fasted rodents. In marked contrast, fasting in black vultures induced decreased rates of incorporation of alanine label into circulating glucose, decreased gluconeogenesis in liver slices, and no change in any of the four enzymes studied. This unusual response to fasting in the carnivorous bird is probably related to the high-protein-low-carbohydrate content of the diet. Fasted adrenalectomized birds (granivorous and carnivorous) had reduced rates of in vivo glucose synthesis, decreased liver gluconeogenesis, and lower activity of glucose-6-phosphatase and aspartate aminotransferase, without change in phosphoenolpyruvate carboxykinase and alanine aminotransferase activities."}
{"id": "PMID:204202", "title": "Angiotensin-converting enzyme in developing lung and kidney.", "content": "Angiontensin-converting enzyme (ACE) catalyzes rapid conversion of angiotensin II (AII). This enzyme has been identified in the vascular endothelium of nearly every tissue. Inasmuch as AII is the biologically active component of the renin-angiotensin system, and since age-related differences exist in the renin-angiotensin system, it was of interest to determine converting enzyme activity during development. ACE activity was quantified by measuring the optical density of hippuric acid liberated from hippuryl-L-histidyl-L-leucine (HHL) following incubation with the 20,000 X g supernatant of tissue homogenates. Pulmonary ACE activity of near-term fetal rats was not different than 1-day-old animals. Therafter, ACE activity increased during the first 6 wk postpartum in a biphasic manner. A similar age-dependent increase in converting enzyme activity was observed in rat kidney, mouse kidney, and mouse lung. Substrate affinity of all enzymes measured was similar, suggesting that the age-related increase in activity was due to increased enzyme content. The low activity of ACE in the newborn might function to limit AII production.", "contents": "Angiotensin-converting enzyme in developing lung and kidney. Angiontensin-converting enzyme (ACE) catalyzes rapid conversion of angiotensin II (AII). This enzyme has been identified in the vascular endothelium of nearly every tissue. Inasmuch as AII is the biologically active component of the renin-angiotensin system, and since age-related differences exist in the renin-angiotensin system, it was of interest to determine converting enzyme activity during development. ACE activity was quantified by measuring the optical density of hippuric acid liberated from hippuryl-L-histidyl-L-leucine (HHL) following incubation with the 20,000 X g supernatant of tissue homogenates. Pulmonary ACE activity of near-term fetal rats was not different than 1-day-old animals. Therafter, ACE activity increased during the first 6 wk postpartum in a biphasic manner. A similar age-dependent increase in converting enzyme activity was observed in rat kidney, mouse kidney, and mouse lung. Substrate affinity of all enzymes measured was similar, suggesting that the age-related increase in activity was due to increased enzyme content. The low activity of ACE in the newborn might function to limit AII production."}
{"id": "PMID:204203", "title": "Patients' views of placement facilities: a participant-observer study.", "content": "The authors report a study in which five student nurses from a psychiatric hospital observed and talked with released patients in their new environments-family care homes, adult and boarding homes, nursing and health-related facilities, and their own family homes. Overall, these ex-inpatients seemed responsive to the physical and social features of their new environments. Some of the aspects most often noted as beneficial may have implications for inpatient facilities in terms of architecture, decor, clear differentiation of subunits, and greater exchange of information between inpatient and field staff.", "contents": "Patients' views of placement facilities: a participant-observer study. The authors report a study in which five student nurses from a psychiatric hospital observed and talked with released patients in their new environments-family care homes, adult and boarding homes, nursing and health-related facilities, and their own family homes. Overall, these ex-inpatients seemed responsive to the physical and social features of their new environments. Some of the aspects most often noted as beneficial may have implications for inpatient facilities in terms of architecture, decor, clear differentiation of subunits, and greater exchange of information between inpatient and field staff."}
{"id": "PMID:204206", "title": "The prevalence of encephalomyocarditis virus neutralizing antibodies among various human populations.", "content": "The prevalence of encephalomyocarditis virus (EMC) antibodies among selected human populations in various regions of the world was determined by the plaque reduction neutralization method. Antibody rates among children ranged from 1.0 to 33.9%, while those among adults varied from 3.2 to 50.6%. No differences between sexes were found in the frequency of EMC infection. The pattern of age-specific antibody rates observed among the study populations suggests that EMC infection occurs primarily during childhood. There appeared to be no association between the presence of EMC antibodies and potential exposure to rats. Sera from diabetic, suspected encephalitis, and myocarditis patients were also examined for EMC neutralizing antibodies. The prevalence of antibodies among these groups was not significantly different from that of control populations in the same geographic regions. No association was demonstrated between EMC infection and these three diseases. The results of this study indicate that EMC infection in man is fairly common but that most human cases are probably asymptomatic and/or unrecognized.", "contents": "The prevalence of encephalomyocarditis virus neutralizing antibodies among various human populations. The prevalence of encephalomyocarditis virus (EMC) antibodies among selected human populations in various regions of the world was determined by the plaque reduction neutralization method. Antibody rates among children ranged from 1.0 to 33.9%, while those among adults varied from 3.2 to 50.6%. No differences between sexes were found in the frequency of EMC infection. The pattern of age-specific antibody rates observed among the study populations suggests that EMC infection occurs primarily during childhood. There appeared to be no association between the presence of EMC antibodies and potential exposure to rats. Sera from diabetic, suspected encephalitis, and myocarditis patients were also examined for EMC neutralizing antibodies. The prevalence of antibodies among these groups was not significantly different from that of control populations in the same geographic regions. No association was demonstrated between EMC infection and these three diseases. The results of this study indicate that EMC infection in man is fairly common but that most human cases are probably asymptomatic and/or unrecognized."}
{"id": "PMID:204207", "title": "Serological evidence of infection of Tacaribe virus and arboviruses in Trinidadian bats.", "content": "Sera from 39 species of bats collected in Trinidad between 1972 and 1974 were tested against some or all of 18 arboviruses in hemagglutination inhibition (HI) and/or suckling mouse neutralization (N) tests. A few sera were HI-positive with Mucambo, eastern equine encephalitis (EEE), Oriboca, Restan, Manzanilla, Guama, Bimiti, and Catu. No sera were HI-positive with Mayaro, Caraparu or Maguari. Many ser inhibited one or more of the group B hemagglutinins: Ilheus, St. Louis encephalitis (SLE), dengue 2, and yellow fever (YF), positives occurred in nearly every species of bat, being most frequent with Ilheus. In N tests, a few or single sera were found to protect against Ilheus, Nepuyo, Guama, Bimiti, and Cocal, while none protected against EEE, SLE, YF or Catu. Many sera positive in HI test with Ilheus, SLE or YF failed to neutralize the respective virus. Tacaribe neutralizing antibody was demonstrated in Artibeus jamaicensis and A. lituratus, the sources of past virus isolation, in the fruit bats Sturnira lilium and Vampyrops helleri, and in the vampire bat Desmodus rotundus. Sera from 19 other species gave either negative or inconclusive results. No convincing evidence of Tacaribe antibody was found in 29 human sera, 20 from bat collectors.", "contents": "Serological evidence of infection of Tacaribe virus and arboviruses in Trinidadian bats. Sera from 39 species of bats collected in Trinidad between 1972 and 1974 were tested against some or all of 18 arboviruses in hemagglutination inhibition (HI) and/or suckling mouse neutralization (N) tests. A few sera were HI-positive with Mucambo, eastern equine encephalitis (EEE), Oriboca, Restan, Manzanilla, Guama, Bimiti, and Catu. No sera were HI-positive with Mayaro, Caraparu or Maguari. Many ser inhibited one or more of the group B hemagglutinins: Ilheus, St. Louis encephalitis (SLE), dengue 2, and yellow fever (YF), positives occurred in nearly every species of bat, being most frequent with Ilheus. In N tests, a few or single sera were found to protect against Ilheus, Nepuyo, Guama, Bimiti, and Cocal, while none protected against EEE, SLE, YF or Catu. Many sera positive in HI test with Ilheus, SLE or YF failed to neutralize the respective virus. Tacaribe neutralizing antibody was demonstrated in Artibeus jamaicensis and A. lituratus, the sources of past virus isolation, in the fruit bats Sturnira lilium and Vampyrops helleri, and in the vampire bat Desmodus rotundus. Sera from 19 other species gave either negative or inconclusive results. No convincing evidence of Tacaribe antibody was found in 29 human sera, 20 from bat collectors."}
{"id": "PMID:204208", "title": "Relevance of laboratory colonies of the vector in arbovirus research--Culicoides variipennis and bluetongue.", "content": "Relevance for laboratory colonies of Culicoides variipennis (Coquillett) in arbovirus research was determined during colonization by comparing a vector-competence characteristic for the parent (P) field and subsequent colonized generations. Three colonies established in 1972-1973 were used to determine whether each was representative of the field population from which it was derived for oral infection to 2 to 4 serotypes of bluetongue virus (BTV). Two colonies that were based on small numbers of females ovipositing did not represent the field population. Both appeared homogeneous to oral infection with different serotypes, and one was resistant to infection whereas the other was susceptible. The third colony, which was based on about 150 P females that had oviposited, was more representative of the field population: 1) oral susceptibility to BTV for the F6 was not greatly different from that of the P generation, and 2) the colony retained some heterogeneity for response to oral infection with different serotypes of BTV. The number and percentage of P females ovipositing and the numerical growth factor from the P to F1 were used to estimate whether a laboratory colony was apt to represent the field population from which it was derived.", "contents": "Relevance of laboratory colonies of the vector in arbovirus research--Culicoides variipennis and bluetongue. Relevance for laboratory colonies of Culicoides variipennis (Coquillett) in arbovirus research was determined during colonization by comparing a vector-competence characteristic for the parent (P) field and subsequent colonized generations. Three colonies established in 1972-1973 were used to determine whether each was representative of the field population from which it was derived for oral infection to 2 to 4 serotypes of bluetongue virus (BTV). Two colonies that were based on small numbers of females ovipositing did not represent the field population. Both appeared homogeneous to oral infection with different serotypes, and one was resistant to infection whereas the other was susceptible. The third colony, which was based on about 150 P females that had oviposited, was more representative of the field population: 1) oral susceptibility to BTV for the F6 was not greatly different from that of the P generation, and 2) the colony retained some heterogeneity for response to oral infection with different serotypes of BTV. The number and percentage of P females ovipositing and the numerical growth factor from the P to F1 were used to estimate whether a laboratory colony was apt to represent the field population from which it was derived."}
{"id": "PMID:204209", "title": "Heterogeneity of Culicoides variipennis field populations to oral infection with bluetongue virus.", "content": "A standard colonized population (000 line) of Culicoides variipennis (Coquillett) was used as the control for comparing the infection rate (IR) responses of different field populations of the vector to oral infection with several strains of bluetongue virus (BTV) that belonged to four serotypes. Three field populations from Colorado and Oregon tested concurrently in 1969 were differently susceptible to three BTV strains representing three serotypes. The IR's of each of the three populations varied greatly for the three serotypes, and the lowest IR for each of two Colorado populations was for a different serotype. The IR's of different populations to the same BTV strain varied greatly, and the lowest and highest IR's for two serotypes with adequate virus concentration occurred in different populations. Two Kentucky field populations in 1971 were completely resistent to oral infection with a BTV strain; in 1972, one population remained resistant and the other became moderately susceptible. The IR's of different field populations in 1971 to a single BTV strain ranged from 0 to 68%. The IR's of an Idaho population to three BTV strains representing three serotypes showed that a susceptibility rate (SR) could be calculated if the IR's were similar for one and for two infective blood meals. The average SR of this population was 42%; the SR's to each serotype were 32%, 40%, and 54%, with the highest response for the serotype that included the BTV strain collected during the BT outbreak from which the vector population was also collected.", "contents": "Heterogeneity of Culicoides variipennis field populations to oral infection with bluetongue virus. A standard colonized population (000 line) of Culicoides variipennis (Coquillett) was used as the control for comparing the infection rate (IR) responses of different field populations of the vector to oral infection with several strains of bluetongue virus (BTV) that belonged to four serotypes. Three field populations from Colorado and Oregon tested concurrently in 1969 were differently susceptible to three BTV strains representing three serotypes. The IR's of each of the three populations varied greatly for the three serotypes, and the lowest IR for each of two Colorado populations was for a different serotype. The IR's of different populations to the same BTV strain varied greatly, and the lowest and highest IR's for two serotypes with adequate virus concentration occurred in different populations. Two Kentucky field populations in 1971 were completely resistent to oral infection with a BTV strain; in 1972, one population remained resistant and the other became moderately susceptible. The IR's of different field populations in 1971 to a single BTV strain ranged from 0 to 68%. The IR's of an Idaho population to three BTV strains representing three serotypes showed that a susceptibility rate (SR) could be calculated if the IR's were similar for one and for two infective blood meals. The average SR of this population was 42%; the SR's to each serotype were 32%, 40%, and 54%, with the highest response for the serotype that included the BTV strain collected during the BT outbreak from which the vector population was also collected."}
{"id": "PMID:204210", "title": "Intracellular demonstration of growth hormone in human mammary carcinoma cells.", "content": "Intracellular growth hormone has been demonstrated in human mammary carcinoma cells by using an unlabeled antibody enzyme technic with horseradish peroxidase and antihorseradish peroxidase complex. Intense reaction was seen in both male and female mammary carcinoma cells. Positive staining was observed in nuclei and cytoplasm and on cytoplasmic membranes.", "contents": "Intracellular demonstration of growth hormone in human mammary carcinoma cells. Intracellular growth hormone has been demonstrated in human mammary carcinoma cells by using an unlabeled antibody enzyme technic with horseradish peroxidase and antihorseradish peroxidase complex. Intense reaction was seen in both male and female mammary carcinoma cells. Positive staining was observed in nuclei and cytoplasm and on cytoplasmic membranes."}
{"id": "PMID:204211", "title": "Alterations in plasma lipid concentrations in normal and hyperlipidemic patients with morbid obesity before and after jejunoileal bypass.", "content": "In a study of 193 massively obese patients plasma lipoprotein concentrations were elevated in 94 patients and were within normal limits in 99 patients. Jejunoileal bypass, in addition to causing weight loss, lowered plasma lipids in both groups to normal or below normal levels.", "contents": "Alterations in plasma lipid concentrations in normal and hyperlipidemic patients with morbid obesity before and after jejunoileal bypass. In a study of 193 massively obese patients plasma lipoprotein concentrations were elevated in 94 patients and were within normal limits in 99 patients. Jejunoileal bypass, in addition to causing weight loss, lowered plasma lipids in both groups to normal or below normal levels."}
{"id": "PMID:204224", "title": "Calcium localization in normal rachitic, and D3-treated chicken epiphyseal chondrocytes utilizing potassium pyroantimonate-osmium tetroxide.", "content": "Normal, rachitic, and vitamin D3-replete chicken growth plates were studied utilizing the potassium pyroantimonate-osmium tetroxide procedure. A marked membrane and mitochondrial calcium was revealed in all specimens in the maturing and early hypertrophic zones which disappeared as heavy matrix mineralization began. The most significant difference shown in the specimens was in the marked intracellular lipid content of chondrocytes in all zones of the rachitic and D3-replete growth plates. There was negligible lipid present in normal specimens. It is suggested that as most of the mechanisms postulated as necessary for calcification are present in rachitic chicks, perhaps the increased intracellular lipid pool results from the formation of abnormal lipids for insertion into the plasma membrane and thus prevents normal calcium transport. Chains of intracellular vesicles were also visualized in maturing and hypertrophic chondrocytes. These were more often seen in rachitic growth plates and in increased numbers in the early D3-replete specimens. The etiology is unknown at the present time.", "contents": "Calcium localization in normal rachitic, and D3-treated chicken epiphyseal chondrocytes utilizing potassium pyroantimonate-osmium tetroxide. Normal, rachitic, and vitamin D3-replete chicken growth plates were studied utilizing the potassium pyroantimonate-osmium tetroxide procedure. A marked membrane and mitochondrial calcium was revealed in all specimens in the maturing and early hypertrophic zones which disappeared as heavy matrix mineralization began. The most significant difference shown in the specimens was in the marked intracellular lipid content of chondrocytes in all zones of the rachitic and D3-replete growth plates. There was negligible lipid present in normal specimens. It is suggested that as most of the mechanisms postulated as necessary for calcification are present in rachitic chicks, perhaps the increased intracellular lipid pool results from the formation of abnormal lipids for insertion into the plasma membrane and thus prevents normal calcium transport. Chains of intracellular vesicles were also visualized in maturing and hypertrophic chondrocytes. These were more often seen in rachitic growth plates and in increased numbers in the early D3-replete specimens. The etiology is unknown at the present time."}
{"id": "PMID:204229", "title": "In vitro antiviral efficacy of ribavirin against feline calicivirus, feline viral rhinotracheitis virus, and canine parainfluenza virus.", "content": "Ribavirin had marked in vitro activity against feline calcivirus, strain 255, and canine parainfluenza virus, but showed only slight antiviral effect on feline viral rhinotracheitis virus. Antiviral activity was manifested by partial to complete suppression of viral cytopathic effect and of viral replication, depending on concentration of ribavirin in the culture medium and dosage of viral inoculum. Concentrations of ribavirin as small as 3.2 microgram/ml and 1.0 microgram/ml showed some activity against feline calcivirus and canine parainfluenza virus, respectively.", "contents": "In vitro antiviral efficacy of ribavirin against feline calicivirus, feline viral rhinotracheitis virus, and canine parainfluenza virus. Ribavirin had marked in vitro activity against feline calcivirus, strain 255, and canine parainfluenza virus, but showed only slight antiviral effect on feline viral rhinotracheitis virus. Antiviral activity was manifested by partial to complete suppression of viral cytopathic effect and of viral replication, depending on concentration of ribavirin in the culture medium and dosage of viral inoculum. Concentrations of ribavirin as small as 3.2 microgram/ml and 1.0 microgram/ml showed some activity against feline calcivirus and canine parainfluenza virus, respectively."}
{"id": "PMID:204230", "title": "Cross reaction between bovine enterovirus and South African Territories I5 foot-and-mouth disease virus.", "content": "A bovine enterovirus (E76T) isolated from a 2-year-old bull produced serologic cross reactions to South African Territories (SAT) I5 foot-and-mouth disease virus when inoculated into guinea pigs and cattle. Cross-reacting serum titers to SAT I5 virus of 1:320 by the plaque-reduction neutralization test and 1:20 by the radial immunodiffusion test occurred in 2 steers after they were inoculated with the E76T virus. In 1 steer, maximal cross-reacting titers appeared related to a 2nd exposure to the viruses or to a hyperimmune state. Ultracentrifugation and 2-mercaptoethanol studies indicated that the cross reactions were due to immunoglobulin M antibody. Sera from guinea pigs immunized with the E76T or the SAT I5 virus cross reacted with the heterologous virus by postinoculation day 7. Cross-reacting titers had decreased markedly by postinoculation day 35, whereas the homologous virus titer remained constant. Cross reactivity of the E76T virus was primarily with the SAT I5 virus, and to a lesser degree with SAT II3. Cross reactions did not occur with representatives of the 5 other antigenic types of foot-and-mouth disease virus.", "contents": "Cross reaction between bovine enterovirus and South African Territories I5 foot-and-mouth disease virus. A bovine enterovirus (E76T) isolated from a 2-year-old bull produced serologic cross reactions to South African Territories (SAT) I5 foot-and-mouth disease virus when inoculated into guinea pigs and cattle. Cross-reacting serum titers to SAT I5 virus of 1:320 by the plaque-reduction neutralization test and 1:20 by the radial immunodiffusion test occurred in 2 steers after they were inoculated with the E76T virus. In 1 steer, maximal cross-reacting titers appeared related to a 2nd exposure to the viruses or to a hyperimmune state. Ultracentrifugation and 2-mercaptoethanol studies indicated that the cross reactions were due to immunoglobulin M antibody. Sera from guinea pigs immunized with the E76T or the SAT I5 virus cross reacted with the heterologous virus by postinoculation day 7. Cross-reacting titers had decreased markedly by postinoculation day 35, whereas the homologous virus titer remained constant. Cross reactivity of the E76T virus was primarily with the SAT I5 virus, and to a lesser degree with SAT II3. Cross reactions did not occur with representatives of the 5 other antigenic types of foot-and-mouth disease virus."}
{"id": "PMID:204226", "title": "Tetanic fade and post-tetanic tension in the absence of neuromuscular blocking agents in anesthetized man.", "content": "Frequency and time dependent changes in neuromuscular transmission were examined in 30 patients undergoing elective minor surgical procedures not requiring the use of muscle relaxants. Anesthesia was induced with sodium thiopenthal and maintained with N2O-O2 and fractional does of meperidine or fentanyl. Neuromuscular function was measured by recording the force of thumb adduction evoked by supramaximal stimulation of the ulnar nerve at the wrist. Single stimuli were applied every 2.5 seconds as square pulses of 0.1-millisecond duration. Tetanic trains of 10-second duration ranging from 10 Hz to 400 Hz were used. From analysis of present data, criteria for normal responses to 10-second tetanic trains of varying frequencies were established. At a frequency of 30 Hz, the tetanic response is fully maintained and followed by post-tetanic potentiation; at a frequency of 50 Hz, both tetanic and post-tetanic responses are maintained; at a frequency of 100 Hz, there is tetanic fade, followed by a post-tetanic depression of the single indirect twitch responses. It is concluded that frequency and duration of indirect stimulation are the most important factors in using tetanic maintenance and post-tetanic events in assessment of recovery from neuromuscular block.", "contents": "Tetanic fade and post-tetanic tension in the absence of neuromuscular blocking agents in anesthetized man. Frequency and time dependent changes in neuromuscular transmission were examined in 30 patients undergoing elective minor surgical procedures not requiring the use of muscle relaxants. Anesthesia was induced with sodium thiopenthal and maintained with N2O-O2 and fractional does of meperidine or fentanyl. Neuromuscular function was measured by recording the force of thumb adduction evoked by supramaximal stimulation of the ulnar nerve at the wrist. Single stimuli were applied every 2.5 seconds as square pulses of 0.1-millisecond duration. Tetanic trains of 10-second duration ranging from 10 Hz to 400 Hz were used. From analysis of present data, criteria for normal responses to 10-second tetanic trains of varying frequencies were established. At a frequency of 30 Hz, the tetanic response is fully maintained and followed by post-tetanic potentiation; at a frequency of 50 Hz, both tetanic and post-tetanic responses are maintained; at a frequency of 100 Hz, there is tetanic fade, followed by a post-tetanic depression of the single indirect twitch responses. It is concluded that frequency and duration of indirect stimulation are the most important factors in using tetanic maintenance and post-tetanic events in assessment of recovery from neuromuscular block."}
{"id": "PMID:204231", "title": "Development and evaluation of a microimmunodiffusion test for detection of antibodies to pseudorabies virus in swine serum.", "content": "A microimmunodiffusion test (MIDT) was developed for the detection of pseudorabies virus (PRV) antibodies in swine serum. The optimal medium for the MIDT was determined to contain 0.69% agarose in 0.05 M tris buffer (pH 7.2) with 0.025% sodium azide and no NaCl. The PRV antigen prepared by (NH4)2SO4 precipitation of viral fluids (42.5 g/100 ml), dialyzed against distilled water, and concentrated to approximately 100-fold of the original volume with polyethylene glycol (mol wt 20,000) provided a good reproducible antigen. The sensitivity of the MIDT was compared with the microtitration procedure of the virus-neutralization (VN) test by assaying 2,203 swine serums for PRV antibodies. An equal percentage of serums was positive in both tests; 419 had VN titers of greater than or equal to 4, and 421 were MIDT positive. Serums (314) that had VN titers of greater than or equal to 16 were all positive by the MIDT. Of serum samples with a VN titer of 8 (53), 50 were MIDT positive, a 94% correlation, and of 52 serums that had VN titers of 4, 36 were MIDT positive, a 69% correlation. In addition, 8 serums that had titer of less than 4 by VN test were positive by MIDT. Seventy-one serum samples were too cytotoxic, markedly hemolyzed, or contaminated to evaluate properly in the VN test; of these serums, 13 were MIDT positive. The MIDT is an accurate, rapid, economical, and sensitive diagnostic test for the detection of PRV antibodies in swine serums.", "contents": "Development and evaluation of a microimmunodiffusion test for detection of antibodies to pseudorabies virus in swine serum. A microimmunodiffusion test (MIDT) was developed for the detection of pseudorabies virus (PRV) antibodies in swine serum. The optimal medium for the MIDT was determined to contain 0.69% agarose in 0.05 M tris buffer (pH 7.2) with 0.025% sodium azide and no NaCl. The PRV antigen prepared by (NH4)2SO4 precipitation of viral fluids (42.5 g/100 ml), dialyzed against distilled water, and concentrated to approximately 100-fold of the original volume with polyethylene glycol (mol wt 20,000) provided a good reproducible antigen. The sensitivity of the MIDT was compared with the microtitration procedure of the virus-neutralization (VN) test by assaying 2,203 swine serums for PRV antibodies. An equal percentage of serums was positive in both tests; 419 had VN titers of greater than or equal to 4, and 421 were MIDT positive. Serums (314) that had VN titers of greater than or equal to 16 were all positive by the MIDT. Of serum samples with a VN titer of 8 (53), 50 were MIDT positive, a 94% correlation, and of 52 serums that had VN titers of 4, 36 were MIDT positive, a 69% correlation. In addition, 8 serums that had titer of less than 4 by VN test were positive by MIDT. Seventy-one serum samples were too cytotoxic, markedly hemolyzed, or contaminated to evaluate properly in the VN test; of these serums, 13 were MIDT positive. The MIDT is an accurate, rapid, economical, and sensitive diagnostic test for the detection of PRV antibodies in swine serums."}
{"id": "PMID:204232", "title": "Pathogenesis of porcine rotaviral infection in experimentally inoculated gnotobiotic pigs.", "content": "Porcine rotavirus was shown to infect gnotobiotic pigs and induce an acute enteric disease clinically characterized by diarrhea, anorexia, depression, and occasional vomition. Onset of clinical signs correlated closely with the appearance of lesions within the small intestinal mucosa, and recovery from infection was associated with the regeneration of normal, functional villous epithelium. Villous atrophy, especially in the caudal two-thirds of the small intestine, was the consistent lesion observed in pigs with clinical signs of rotaviral infection. Villi were often short, blunt, and covered with cuboidal epithelial cells. Immunofluorescent microscopy methods demonstrated that the principal site of rotaviral replication was the villous columnar epithelial cells in the small intestine.", "contents": "Pathogenesis of porcine rotaviral infection in experimentally inoculated gnotobiotic pigs. Porcine rotavirus was shown to infect gnotobiotic pigs and induce an acute enteric disease clinically characterized by diarrhea, anorexia, depression, and occasional vomition. Onset of clinical signs correlated closely with the appearance of lesions within the small intestinal mucosa, and recovery from infection was associated with the regeneration of normal, functional villous epithelium. Villous atrophy, especially in the caudal two-thirds of the small intestine, was the consistent lesion observed in pigs with clinical signs of rotaviral infection. Villi were often short, blunt, and covered with cuboidal epithelial cells. Immunofluorescent microscopy methods demonstrated that the principal site of rotaviral replication was the villous columnar epithelial cells in the small intestine."}
{"id": "PMID:204233", "title": "Maternal immunity to infectious bovine rhinotracheitis and bovine viral diarrhea viruses: duration and effect on vaccination in young calves.", "content": "The immune response to modified live-virus bovine viral diarrhea (BVD) vaccine and infectious bovine rhinotracheitis (IBR) vaccine was examined in calves that had received passive maternal antibodies to these viruses. Blood serum samples from vaccinated and control (nonvaccinated) calves were examined for more than 1 year to determine the rate of decline of passive anti-BVD and anti-IBR antibodies and the effect that vaccination had on these antibody titers. The control calves lost their antibodies to BVD and IBR viruses at the rate of one half their remaining antibody titer every 21 days. Calves serologically responded to BVD vaccine at a time when maternal antibody titers remained between 1:96 and 1:20. However, animals did not seroconvert to the IBR vaccine until maternal antibodies had decreased and become undetectable. Evidence is presented to show that although passive immunity will inhibit IBR vaccination, priming for a secondary response will occur so that on subsequent vaccination, at a time when maternal antibodies have disappeared, the animals will respond anamnestically to IBR vaccination.", "contents": "Maternal immunity to infectious bovine rhinotracheitis and bovine viral diarrhea viruses: duration and effect on vaccination in young calves. The immune response to modified live-virus bovine viral diarrhea (BVD) vaccine and infectious bovine rhinotracheitis (IBR) vaccine was examined in calves that had received passive maternal antibodies to these viruses. Blood serum samples from vaccinated and control (nonvaccinated) calves were examined for more than 1 year to determine the rate of decline of passive anti-BVD and anti-IBR antibodies and the effect that vaccination had on these antibody titers. The control calves lost their antibodies to BVD and IBR viruses at the rate of one half their remaining antibody titer every 21 days. Calves serologically responded to BVD vaccine at a time when maternal antibody titers remained between 1:96 and 1:20. However, animals did not seroconvert to the IBR vaccine until maternal antibodies had decreased and become undetectable. Evidence is presented to show that although passive immunity will inhibit IBR vaccination, priming for a secondary response will occur so that on subsequent vaccination, at a time when maternal antibodies have disappeared, the animals will respond anamnestically to IBR vaccination."}
{"id": "PMID:204234", "title": "Studies on adjuvant-induced arthritis, tumor transplantability, and serologic response to bovine serum albumin in Sendai virus-infected rats.", "content": "Sendai virus, one of the most prevalent of the murine viruses, was studied in regard to its capability to alter various functions of rats given a second, unrelated antigenic challenge. Rats given a single foot-pad injection of Freund's complete adjuvant (FCA) had an 85% incidence of adjuvant arthritis. The adjuvant disease was significantly less severe (P less than 0.01) in those rats given 0.05 ml of 10(5.5) median egg infective doses of egg-propagated Sendai virus intranasally 7 days before injection of adjuvant. Rats given Sendai virus concurrently with the FCA, or any time after FCA was injected, did not have a lessened severity of the arthritic reaction, as compared with that in control animals. Sendai virus infection had no detectable effect on median tumor dose requirement for Walker carcinosarcoma cells in rats or on the antibody response to bovine serum albumin.", "contents": "Studies on adjuvant-induced arthritis, tumor transplantability, and serologic response to bovine serum albumin in Sendai virus-infected rats. Sendai virus, one of the most prevalent of the murine viruses, was studied in regard to its capability to alter various functions of rats given a second, unrelated antigenic challenge. Rats given a single foot-pad injection of Freund's complete adjuvant (FCA) had an 85% incidence of adjuvant arthritis. The adjuvant disease was significantly less severe (P less than 0.01) in those rats given 0.05 ml of 10(5.5) median egg infective doses of egg-propagated Sendai virus intranasally 7 days before injection of adjuvant. Rats given Sendai virus concurrently with the FCA, or any time after FCA was injected, did not have a lessened severity of the arthritic reaction, as compared with that in control animals. Sendai virus infection had no detectable effect on median tumor dose requirement for Walker carcinosarcoma cells in rats or on the antibody response to bovine serum albumin."}
{"id": "PMID:204235", "title": "Transmission of Aleutian disease from mink with inapparent infections.", "content": "In apparent or nonprogressive Aleutian disease virus infection was considered a subclinical but persistent viral infection in which infected mink did not develop tissue lesions, hypergammaglobulinemia, or high antibody titers. Transmission of Aleutian disease virus from mink with this type of infection was measured. Mink with inapparent Aleutian disease appeared healthy and had normal gamma-globulin values, but were capable of transmitting the disease by direct and indirect horizontal contact. The risk of direct or indirect horizontal transmission from mink with inapparent infection was less than from mink with progressive Aleutian disease. Infection also was directly transmitted from the dam to the kits, but again the risk of infection from dams with inapparent infection was less than from dams with progressive Aleutian disease. Mink infected from their dams before weaning developed the disease more slowly than mink which became infected after weaning.", "contents": "Transmission of Aleutian disease from mink with inapparent infections. In apparent or nonprogressive Aleutian disease virus infection was considered a subclinical but persistent viral infection in which infected mink did not develop tissue lesions, hypergammaglobulinemia, or high antibody titers. Transmission of Aleutian disease virus from mink with this type of infection was measured. Mink with inapparent Aleutian disease appeared healthy and had normal gamma-globulin values, but were capable of transmitting the disease by direct and indirect horizontal contact. The risk of direct or indirect horizontal transmission from mink with inapparent infection was less than from mink with progressive Aleutian disease. Infection also was directly transmitted from the dam to the kits, but again the risk of infection from dams with inapparent infection was less than from dams with progressive Aleutian disease. Mink infected from their dams before weaning developed the disease more slowly than mink which became infected after weaning."}
{"id": "PMID:204236", "title": "Immunologic \"memory\" for microbial antigens in lymphocytes obtained from human bronchial mucosa.", "content": "Memory for previous immunologic contact with microbial antigens has been detected in lymphocytes from human bronchi as a secondary immune response, when tested in vitro. Antigens stimulated a predominantly proliferative response in blood lymphocytes that was significantly greater than the response in mucosal lymphocytes with purified protein derivative and Herpes simplex type 1 antigens. Co-culture experiments with autologous blood lymphocytes showed that cell-dependent suppression was one mechanism of the low response of bronchial lymphocytes. In the patient who inhaled a foreign body, a proliferative response to antigens was restricted to bronchus-associated lymphoid tissue lymphocytes, suggesting a recruitment of antigen-reactive cells from a circulating pool.", "contents": "Immunologic \"memory\" for microbial antigens in lymphocytes obtained from human bronchial mucosa. Memory for previous immunologic contact with microbial antigens has been detected in lymphocytes from human bronchi as a secondary immune response, when tested in vitro. Antigens stimulated a predominantly proliferative response in blood lymphocytes that was significantly greater than the response in mucosal lymphocytes with purified protein derivative and Herpes simplex type 1 antigens. Co-culture experiments with autologous blood lymphocytes showed that cell-dependent suppression was one mechanism of the low response of bronchial lymphocytes. In the patient who inhaled a foreign body, a proliferative response to antigens was restricted to bronchus-associated lymphoid tissue lymphocytes, suggesting a recruitment of antigen-reactive cells from a circulating pool."}
{"id": "PMID:204238", "title": "Dual radionuclide study of acute myocardial infarction: comparison of thallium-201 and technetium-99m stannous prophosphate imaging in man.", "content": "We evaluated dual imaging with thalium-201 (201TI) and technetium-99m (99mTc) pyrophosphate in 80 patients with documented acute myocardial infarction (55 transmural, 25 nontransmural infarction). Color-coded isocount display of 201TI images was essential for interpretation in 16 patients. Combined 201 TI and 99mTc-pyrophosphate imaging for infarct detection was 100% sensitive; however, either was falsely negative in 12 of 80 patients. False-negative individual 201TI or 99mTc-pyrophosphate infarct images were most common in patients with small infacts or left ventricular hypertrophy. Thallium-201 images correctly localized the site of acute transmural infarction in all 51 patients with a positive image, while 99mTc-pyrophosphate localized the site of infarction in 49 of 53 with an abnormal image. Comparison of the size of the imaged infarct region revealed size discordance in 25 of 49 patinets, with 99mTc-pyrophosphate larger in 21 of 49 and 201TI larger in only four of 49. Thus dual radionuclide imaging provides definition of the presence and location of acute myocardial infarction.", "contents": "Dual radionuclide study of acute myocardial infarction: comparison of thallium-201 and technetium-99m stannous prophosphate imaging in man. We evaluated dual imaging with thalium-201 (201TI) and technetium-99m (99mTc) pyrophosphate in 80 patients with documented acute myocardial infarction (55 transmural, 25 nontransmural infarction). Color-coded isocount display of 201TI images was essential for interpretation in 16 patients. Combined 201 TI and 99mTc-pyrophosphate imaging for infarct detection was 100% sensitive; however, either was falsely negative in 12 of 80 patients. False-negative individual 201TI or 99mTc-pyrophosphate infarct images were most common in patients with small infacts or left ventricular hypertrophy. Thallium-201 images correctly localized the site of acute transmural infarction in all 51 patients with a positive image, while 99mTc-pyrophosphate localized the site of infarction in 49 of 53 with an abnormal image. Comparison of the size of the imaged infarct region revealed size discordance in 25 of 49 patinets, with 99mTc-pyrophosphate larger in 21 of 49 and 201TI larger in only four of 49. Thus dual radionuclide imaging provides definition of the presence and location of acute myocardial infarction."}
{"id": "PMID:204239", "title": "Small-cell carcinoma of the lung: combined chemotherapy and radiation: a Southwest Oncology Group study.", "content": "Chemotherapy (doxorubicin, cyclophosphamide, and vincristine) was given in a sequential fashion with radiation of the primary tumor and brain to 358 patients with small-cell lung carcinoma (extensive disease in 250, limited in 108). Complete regression of tumor was obtained in 14% of patients with extensive disease and 41% of patients with limited disease, and complete or partial response in 57% and 75%, respectively. Median survival was 26 weeks for patients with extensive disease and 52 weeks for those with limited disease. Response duration was longer for patients in complete remission; one third had disease-free survival greater than 1 year. Toxicity from the combined treatment modalities was no greater than expected from the components given separately: fatal in 3.9%, and life-threatening but reversible in 8.4% of patients. Whole-brain radiation was effective in preventing isolated relapse at that site. This therapy appears both feasible and effective, with acceptable risks and some benefit to most patients.", "contents": "Small-cell carcinoma of the lung: combined chemotherapy and radiation: a Southwest Oncology Group study. Chemotherapy (doxorubicin, cyclophosphamide, and vincristine) was given in a sequential fashion with radiation of the primary tumor and brain to 358 patients with small-cell lung carcinoma (extensive disease in 250, limited in 108). Complete regression of tumor was obtained in 14% of patients with extensive disease and 41% of patients with limited disease, and complete or partial response in 57% and 75%, respectively. Median survival was 26 weeks for patients with extensive disease and 52 weeks for those with limited disease. Response duration was longer for patients in complete remission; one third had disease-free survival greater than 1 year. Toxicity from the combined treatment modalities was no greater than expected from the components given separately: fatal in 3.9%, and life-threatening but reversible in 8.4% of patients. Whole-brain radiation was effective in preventing isolated relapse at that site. This therapy appears both feasible and effective, with acceptable risks and some benefit to most patients."}
{"id": "PMID:204240", "title": "Colorado tick fever: clinical, epidemiologic, and laboratory aspects of 228 cases in Colorado in 1973-1974.", "content": "During 1973 and 1974, we looked for cases of Colorado tick fever throughout Colorado; 228 cases were identified. Although 90% of the patients reported exposure to ticks before illness, only 52% were aware of an actual tick bite. Typical symptoms of fever, myalgia, and headache were common, but gastrointestinal symptoms were also prominent in 20% of the patients. Twenty percent were hospitalized; no deaths or permanent sequelae were noted. Persistent viremia (greater than or equal to 4 weeks) was found in about half of the cases; this finding was not associated with the occurrence of prolonged symptoms (greater than or equal to 3 weeks), which were also reported in half of the cases. One patient became reinfected with the virus. Increasing tourism in endemic areas and the frequent occurrence of prolonged or biphasic illnesses provide the potential for patients with Colorado tick fever to seek medical care anywhere in the United States.", "contents": "Colorado tick fever: clinical, epidemiologic, and laboratory aspects of 228 cases in Colorado in 1973-1974. During 1973 and 1974, we looked for cases of Colorado tick fever throughout Colorado; 228 cases were identified. Although 90% of the patients reported exposure to ticks before illness, only 52% were aware of an actual tick bite. Typical symptoms of fever, myalgia, and headache were common, but gastrointestinal symptoms were also prominent in 20% of the patients. Twenty percent were hospitalized; no deaths or permanent sequelae were noted. Persistent viremia (greater than or equal to 4 weeks) was found in about half of the cases; this finding was not associated with the occurrence of prolonged symptoms (greater than or equal to 3 weeks), which were also reported in half of the cases. One patient became reinfected with the virus. Increasing tourism in endemic areas and the frequent occurrence of prolonged or biphasic illnesses provide the potential for patients with Colorado tick fever to seek medical care anywhere in the United States."}
{"id": "PMID:204241", "title": "UCLA conference. Autoimmune thyroid diseases--Graves' and Hashimoto's.", "content": "Thyroid-related autoimmune diseases (Graves' thyroid disease, Graves' ophthalmopathy, and Hashimoto's thyroiditis) may occur alone or in any association. The diagnosis of Hashimoto's thyroiditis requires multiple criteria; pathologic changes in the thyroid are not due to antibodies but may result from cytotoxic lymphocytes or a deficiency of suppressive T cells. In Graves' and Hashimoto's diseases the increased prevalence of HLA-B8 may not be significant, but that of HLA-AW30 in Hashimoto's disease is. In 48 first-degree relatives of patients with Graves' disease, thyroid abnormalities were frequent but not correlated with HLA type. Elevated serum thyroglobulin levels in all patients with hyperthyroidism fell to normal after surgical resection or radioiodine therapy. Patients whose illness recurred after antithyroid drug treatment was stopped had higher pretreatment thyroglobulin levels and no fall during treatment; those whose illness remitted had lower initial levels and a significant fall during treatment. Sodium ipodate lowered serum triiodothyronine and thyroxine levels in hyperthyroid patients and may be useful in the treatment of hyperthyroidism.", "contents": "UCLA conference. Autoimmune thyroid diseases--Graves' and Hashimoto's. Thyroid-related autoimmune diseases (Graves' thyroid disease, Graves' ophthalmopathy, and Hashimoto's thyroiditis) may occur alone or in any association. The diagnosis of Hashimoto's thyroiditis requires multiple criteria; pathologic changes in the thyroid are not due to antibodies but may result from cytotoxic lymphocytes or a deficiency of suppressive T cells. In Graves' and Hashimoto's diseases the increased prevalence of HLA-B8 may not be significant, but that of HLA-AW30 in Hashimoto's disease is. In 48 first-degree relatives of patients with Graves' disease, thyroid abnormalities were frequent but not correlated with HLA type. Elevated serum thyroglobulin levels in all patients with hyperthyroidism fell to normal after surgical resection or radioiodine therapy. Patients whose illness recurred after antithyroid drug treatment was stopped had higher pretreatment thyroglobulin levels and no fall during treatment; those whose illness remitted had lower initial levels and a significant fall during treatment. Sodium ipodate lowered serum triiodothyronine and thyroxine levels in hyperthyroid patients and may be useful in the treatment of hyperthyroidism."}
{"id": "PMID:204244", "title": "Comparison of three automated methods of serum tirglyceride analysis.", "content": "Two new automated methods for serum triglyceride analysis are described and compared with each other and with an established chemical method. They are a chemical method requiring no glycerol blank correction and a commercially available fully enzymatic method requiring no prior lipid extraction. Both methods had higher quality control precision and faster sampling rates than the established method. Comparison of duplicate analyses of a random series of serum samples by all three methods gave a closer correlation between the new methods than between either and the conventional method.", "contents": "Comparison of three automated methods of serum tirglyceride analysis. Two new automated methods for serum triglyceride analysis are described and compared with each other and with an established chemical method. They are a chemical method requiring no glycerol blank correction and a commercially available fully enzymatic method requiring no prior lipid extraction. Both methods had higher quality control precision and faster sampling rates than the established method. Comparison of duplicate analyses of a random series of serum samples by all three methods gave a closer correlation between the new methods than between either and the conventional method."}
{"id": "PMID:204245", "title": "Direct measurement of cGMP in blood plasma and urine by radioimmunoassay.", "content": "Antisera, raised against 2'-O-succinyl-cGMP conjugated to ovalbumin or kehole limpet haemocyanin, have been used to develop radioimmunoassays for the direct determination of urine and plasma cGMP levels. Details of these assays are presented, together with evidence for their validity.", "contents": "Direct measurement of cGMP in blood plasma and urine by radioimmunoassay. Antisera, raised against 2'-O-succinyl-cGMP conjugated to ovalbumin or kehole limpet haemocyanin, have been used to develop radioimmunoassays for the direct determination of urine and plasma cGMP levels. Details of these assays are presented, together with evidence for their validity."}
{"id": "PMID:204246", "title": "Segregation of ABO, AK1 and ACONs in families with abnormalities of chromosome 9.", "content": "Some families with abnormalities of chromosome 9 have been combined with others from the literature to show that AK1 and ABO must lie near the end of that chromosome. Current evidence suggests that both lie in band 9q34. MNSs, GPT and Gc can be excluded from chromosome 9.", "contents": "Segregation of ABO, AK1 and ACONs in families with abnormalities of chromosome 9. Some families with abnormalities of chromosome 9 have been combined with others from the literature to show that AK1 and ABO must lie near the end of that chromosome. Current evidence suggests that both lie in band 9q34. MNSs, GPT and Gc can be excluded from chromosome 9."}
{"id": "PMID:204247", "title": "[Action of aureolic acid and dactinomycin group antibiotics on human brain tumors in culture].", "content": "The cytotoxic effect of antitumour antibiotics, such as dactinomycin, mithramycin, variamycin and olivomycin on the cells of the human brain tumours (multiform glyoblastoma, arachnoidendotelioma and astrocytoma) grown by the method of the primary plasmic culture was studied. Dactinomycin was superior to the antibiotics of the aureolic acid group in the rate and level of the cytotoxic effect on the tumour cells: 76 per cent of the above tumours were sensitive to dactinomycin, 56 per cent to mithramycin and 52 per cent to variamycin and olivomycin. Among the total number of the tumours sensitive to the drugs the number of the highly sensitive tumours amounted to 57.9 per cent for dactinomycin and 30.8--38.5 per cent for the antibiotics of the aureolic acid group. Definite differences in the efficiency of the antibiotics of the aureolic acid group with respect to different types of the brain tumours were observed.", "contents": "[Action of aureolic acid and dactinomycin group antibiotics on human brain tumors in culture]. The cytotoxic effect of antitumour antibiotics, such as dactinomycin, mithramycin, variamycin and olivomycin on the cells of the human brain tumours (multiform glyoblastoma, arachnoidendotelioma and astrocytoma) grown by the method of the primary plasmic culture was studied. Dactinomycin was superior to the antibiotics of the aureolic acid group in the rate and level of the cytotoxic effect on the tumour cells: 76 per cent of the above tumours were sensitive to dactinomycin, 56 per cent to mithramycin and 52 per cent to variamycin and olivomycin. Among the total number of the tumours sensitive to the drugs the number of the highly sensitive tumours amounted to 57.9 per cent for dactinomycin and 30.8--38.5 per cent for the antibiotics of the aureolic acid group. Definite differences in the efficiency of the antibiotics of the aureolic acid group with respect to different types of the brain tumours were observed."}
{"id": "PMID:204248", "title": "[Use of prodigiozan for preventing acute respiratory viral diseases in a children's collective].", "content": "The epidemiological efficacy of 0.02 per cent solution of prodigiosan, a bacterial polysaccharide was used for the treatment of children in an area with acute respiratory infections, such as influenza and parainfluenza. The drug was administered intranasally by means of a dosing sprayer in the amounts of 0.2 ml once in 4 days for 4 months. Among the children treated with prodigiosan the rate of the acute respiratory viral infections was 2 times lower and the average duration of the disease was 2.4 times lower as compared to the control group. After 4 months of the drug use the average value of the \"skin autoflora\" test was much lower than that in the control group which testified to an increase in the non-specific immunobiological reactivity of the children under the effect of prodigiosan.", "contents": "[Use of prodigiozan for preventing acute respiratory viral diseases in a children's collective]. The epidemiological efficacy of 0.02 per cent solution of prodigiosan, a bacterial polysaccharide was used for the treatment of children in an area with acute respiratory infections, such as influenza and parainfluenza. The drug was administered intranasally by means of a dosing sprayer in the amounts of 0.2 ml once in 4 days for 4 months. Among the children treated with prodigiosan the rate of the acute respiratory viral infections was 2 times lower and the average duration of the disease was 2.4 times lower as compared to the control group. After 4 months of the drug use the average value of the \"skin autoflora\" test was much lower than that in the control group which testified to an increase in the non-specific immunobiological reactivity of the children under the effect of prodigiosan."}
{"id": "PMID:204249", "title": "Deoxyribonucleic acid polymerase of wild-type and phosphonoacetic acid-resistant mutant of herpes simplex virus.", "content": "The phosphonacetic acid (PAA)-susceptible deoxyribonucleic acid (DNA) polymerase of herpes simplex virus type 1 was partially purified and isolated in sucrose gradients and on double-strand DNA cellulose columns. The DNA polymerase isolated from cells infected with the PAA-resistant mutant had the same molecular weight as the wild-type enzyme (140,000 to 149,000) but was consistently more resistant to PAA.", "contents": "Deoxyribonucleic acid polymerase of wild-type and phosphonoacetic acid-resistant mutant of herpes simplex virus. The phosphonacetic acid (PAA)-susceptible deoxyribonucleic acid (DNA) polymerase of herpes simplex virus type 1 was partially purified and isolated in sucrose gradients and on double-strand DNA cellulose columns. The DNA polymerase isolated from cells infected with the PAA-resistant mutant had the same molecular weight as the wild-type enzyme (140,000 to 149,000) but was consistently more resistant to PAA."}
{"id": "PMID:204250", "title": "Alteration of mortality and pathogenesis of three experimental Herpesvirus hominis infections of mice with adenine arabinoside 5'-monophosphate, adenine arabinoside, and phosphonoacetic acid.", "content": "The therapeutic effectiveness of adenine arabinoside 5'-monophosphate (ara-AMP), adenine arabinoside (ara-A), and phosphonoacetic acid (PAA) was compared in three experimental Herpesvirus hominis type 2 infections of mice. In animals inoculated with H. hominis by the intracerebral or intraperitoneal route, both ara-AMP and ara-A were highly effective in reducing mortality even when treatment was begun 48 to 96 h after viral inoculation. ara-AMP was the most effective in both models in that treatment could be initiated 24 to 48 h later in the course of infection than with ara-A and still confer significant protection. In mice inoculated intraperitoneally, protection due to ara-AMP therapy was associated with reduced replication of virus in visceral organs and complete inhibition of transmission of virus to the brain. PAA treatment of mice inoculated intraperitoneally was effective in reducing mortality only if initiated shortly after infection. Treatment with PAA did not reduce mortality of mice inoculated intracerebrally but did prolong the mean day of death. When mice were inoculated intranasally with H. hominis, none of the three drugs altered final mortality; however, treatment with ara-AMP did prolong the mean day of death. Treatment with ara-AMP effectively reduced viral replication in the lung and liver in this model infection, but failed to prevent transmission of virus through the trigeminal nerves from the nasopharynx to the brain.", "contents": "Alteration of mortality and pathogenesis of three experimental Herpesvirus hominis infections of mice with adenine arabinoside 5'-monophosphate, adenine arabinoside, and phosphonoacetic acid. The therapeutic effectiveness of adenine arabinoside 5'-monophosphate (ara-AMP), adenine arabinoside (ara-A), and phosphonoacetic acid (PAA) was compared in three experimental Herpesvirus hominis type 2 infections of mice. In animals inoculated with H. hominis by the intracerebral or intraperitoneal route, both ara-AMP and ara-A were highly effective in reducing mortality even when treatment was begun 48 to 96 h after viral inoculation. ara-AMP was the most effective in both models in that treatment could be initiated 24 to 48 h later in the course of infection than with ara-A and still confer significant protection. In mice inoculated intraperitoneally, protection due to ara-AMP therapy was associated with reduced replication of virus in visceral organs and complete inhibition of transmission of virus to the brain. PAA treatment of mice inoculated intraperitoneally was effective in reducing mortality only if initiated shortly after infection. Treatment with PAA did not reduce mortality of mice inoculated intracerebrally but did prolong the mean day of death. When mice were inoculated intranasally with H. hominis, none of the three drugs altered final mortality; however, treatment with ara-AMP did prolong the mean day of death. Treatment with ara-AMP effectively reduced viral replication in the lung and liver in this model infection, but failed to prevent transmission of virus through the trigeminal nerves from the nasopharynx to the brain."}
{"id": "PMID:204256", "title": "The glucagonoma syndrome. A distinctive cutaneous marker of systemic disease.", "content": "The glucagonoma syndrome is a rare clinical condition characterized by a distinctive cutaneous eruption associated with a glucagon-secreting islet cell neoplasm of the pancreas. A 19-year-old woman manifested typical features of this condition: a polymorphous skin eruption with characteristic distribution of lesions in perioral and paragenital regions; lesions in sites of cutaneous trauma; a skin biopsy that showed epidermal cleavage; glossitis; weight loss; mild anemia; abnormal glucose tolerance test results. Plasma glucagon levels, determined by radioimmunoassay, were approximately five times normal. Angiography indicated a pancreatic tumor with liver metastases. Islet cell origin was confirmed histologically. It is hoped that wider recognition of the distinctive clinical features of this syndrome will result in earlier detection and possible surgical cure of the underlying malignancy.", "contents": "The glucagonoma syndrome. A distinctive cutaneous marker of systemic disease. The glucagonoma syndrome is a rare clinical condition characterized by a distinctive cutaneous eruption associated with a glucagon-secreting islet cell neoplasm of the pancreas. A 19-year-old woman manifested typical features of this condition: a polymorphous skin eruption with characteristic distribution of lesions in perioral and paragenital regions; lesions in sites of cutaneous trauma; a skin biopsy that showed epidermal cleavage; glossitis; weight loss; mild anemia; abnormal glucose tolerance test results. Plasma glucagon levels, determined by radioimmunoassay, were approximately five times normal. Angiography indicated a pancreatic tumor with liver metastases. Islet cell origin was confirmed histologically. It is hoped that wider recognition of the distinctive clinical features of this syndrome will result in earlier detection and possible surgical cure of the underlying malignancy."}
{"id": "PMID:204257", "title": "Primary adenoid cystic carcinoma of skin.", "content": "Two primary adenoid cystic carcinomas of skin were studied histologically and histochemically. Histologically, they closely resemble adenoid cystic carcinoma found in other tissues but in the skin must be distinguished from aggressive basal cell carcinomas. The natural history of these tumors and of those collected from the literature suggest a long indolent and progressive course. Local excision with meticulous histologic control of the surgical margins appears to be an appropriate therapeutic strategy. Thus far lymph node metastases have not been observed.", "contents": "Primary adenoid cystic carcinoma of skin. Two primary adenoid cystic carcinomas of skin were studied histologically and histochemically. Histologically, they closely resemble adenoid cystic carcinoma found in other tissues but in the skin must be distinguished from aggressive basal cell carcinomas. The natural history of these tumors and of those collected from the literature suggest a long indolent and progressive course. Local excision with meticulous histologic control of the surgical margins appears to be an appropriate therapeutic strategy. Thus far lymph node metastases have not been observed."}
{"id": "PMID:204263", "title": "An analysis of cytomegalovirus infection and HLA antigen matching on the outcome of renal transplantation.", "content": "Eighty-five recipients and donors of renal allografts were examined for evidence of cytomegalovirus infection before and repeatedly after transplantation. The recipients were also divided into two group on the basis of HLA antigen matching. Better allograft survival was noted in patients well matched for HLA antigens (0-2) mismatched antigens) compared to those poorly matched (three or more antigens mismatched), and in patients free of cytomegalovirus compared to those infected. Cytomegalovirus infection had a more marked influence on allograft survival than did HLA antigen matching. The differing rates of success of transplantation, apparently dependent on blood relationship between donor and recipient, have been assumed largely to be due to inherited factors. This study, however, revealed an important factor to be the disparate incidence of cytomegalovirus infection in sibling, parental, and cadaveric categories of transplantation. The mechanism of this disparity can be explained on the basis of the incidence of latent CMV infection in the recipients and various categories of kidney donors.", "contents": "An analysis of cytomegalovirus infection and HLA antigen matching on the outcome of renal transplantation. Eighty-five recipients and donors of renal allografts were examined for evidence of cytomegalovirus infection before and repeatedly after transplantation. The recipients were also divided into two group on the basis of HLA antigen matching. Better allograft survival was noted in patients well matched for HLA antigens (0-2) mismatched antigens) compared to those poorly matched (three or more antigens mismatched), and in patients free of cytomegalovirus compared to those infected. Cytomegalovirus infection had a more marked influence on allograft survival than did HLA antigen matching. The differing rates of success of transplantation, apparently dependent on blood relationship between donor and recipient, have been assumed largely to be due to inherited factors. This study, however, revealed an important factor to be the disparate incidence of cytomegalovirus infection in sibling, parental, and cadaveric categories of transplantation. The mechanism of this disparity can be explained on the basis of the incidence of latent CMV infection in the recipients and various categories of kidney donors."}
{"id": "PMID:204264", "title": "Anaerobic septicemia after transrectal prostatic biopsy.", "content": "Transrectal biopsy of the prostate resulted in anaerobic septicemia in two patients, despite parenteral gentamicin sulfate prophylaxis. Bacteroides fragilis sepsis developed subacutely in one patient having a postbiopsy pelvic abscess. Clostridium perfringens sepsis occurred fulminantly in another patient 24 hours after biopsy of a gland extensively involved with adenocarcinoma. These cases indicate a potential hazard of sepsis due to anaerobic contamination with rectal microflora at the time of transrectal prostatic biopsy and the futility of prophylaxis directed only at aerobic bacteria.", "contents": "Anaerobic septicemia after transrectal prostatic biopsy. Transrectal biopsy of the prostate resulted in anaerobic septicemia in two patients, despite parenteral gentamicin sulfate prophylaxis. Bacteroides fragilis sepsis developed subacutely in one patient having a postbiopsy pelvic abscess. Clostridium perfringens sepsis occurred fulminantly in another patient 24 hours after biopsy of a gland extensively involved with adenocarcinoma. These cases indicate a potential hazard of sepsis due to anaerobic contamination with rectal microflora at the time of transrectal prostatic biopsy and the futility of prophylaxis directed only at aerobic bacteria."}
{"id": "PMID:204260", "title": "[Effects of cholera toxin on the regenerating rat liver (author's transl)].", "content": "Two groups of animals were treated with cholera toxin respectively with 10,000 B.D. and 20,000 B.D. soon after hepatectomy. The parameters used were: the percentage of liver regeneration, mytotic activity and the liver protein content. The resulting differences between the controls and the two groups of animals treated were not statistically significant. The Authors conclude that cholera toxin does not affect the liver regeneration in the rat.", "contents": "[Effects of cholera toxin on the regenerating rat liver (author's transl)]. Two groups of animals were treated with cholera toxin respectively with 10,000 B.D. and 20,000 B.D. soon after hepatectomy. The parameters used were: the percentage of liver regeneration, mytotic activity and the liver protein content. The resulting differences between the controls and the two groups of animals treated were not statistically significant. The Authors conclude that cholera toxin does not affect the liver regeneration in the rat."}
{"id": "PMID:204265", "title": "Hyperchloremia and negative anion gap associated with polymyxin B administration.", "content": "A patient receiving polymyxin B sulfate intravenously for Gram-negative \"anion gap\". Both abnormalities resolved following discontinuation of the drug. In vitro investigation suggested that the electrolyte abnormalities resulted from the polycationic properties of polymyxin B.", "contents": "Hyperchloremia and negative anion gap associated with polymyxin B administration. A patient receiving polymyxin B sulfate intravenously for Gram-negative \"anion gap\". Both abnormalities resolved following discontinuation of the drug. In vitro investigation suggested that the electrolyte abnormalities resulted from the polycationic properties of polymyxin B."}
{"id": "PMID:204261", "title": "[The enzyme-linked immunosorbent assay (ELISA) in the diagnosis of amoebiasis (author's transl)].", "content": "An enzyme-linked immunosorbent assay (ELISA) technique as an aid to the detection of antibodies to Entamoeba histolytica has been evaluated in four groups of 39 individuals. Results were positive in 15 patients with amoebic dysentery harboring trophozoites of Entamoeba histolytica, in their stools; negative in 6 patients with enteric symptoms whose faeces contained neither trophozoites nor cysts of Entamoeba histolytica, in 8 patients with other parasitic diseases in whom clinical examination was not indicative of infection with Entamoeba histolytica, and in 10 sera from blood-donors. The ELISA has been shown to be a sensitive method of detecting antibodies to entamoeba histolytica.", "contents": "[The enzyme-linked immunosorbent assay (ELISA) in the diagnosis of amoebiasis (author's transl)]. An enzyme-linked immunosorbent assay (ELISA) technique as an aid to the detection of antibodies to Entamoeba histolytica has been evaluated in four groups of 39 individuals. Results were positive in 15 patients with amoebic dysentery harboring trophozoites of Entamoeba histolytica, in their stools; negative in 6 patients with enteric symptoms whose faeces contained neither trophozoites nor cysts of Entamoeba histolytica, in 8 patients with other parasitic diseases in whom clinical examination was not indicative of infection with Entamoeba histolytica, and in 10 sera from blood-donors. The ELISA has been shown to be a sensitive method of detecting antibodies to entamoeba histolytica."}
{"id": "PMID:204267", "title": "Varicella-zoster virus infection of human brain cells and ganglion cells in tissue culture.", "content": "The growth of varicella-zoster virus (VZV) in cultures of human brain (HB) and human ganglion (HG) cells was compared to VZV growth in human fibroblasts. Infected cultures were monitored by histologic, electron microscopic (EM), and virologic techniques. Two to three days after VZV infection of all cell cultures at a multiplicity of infection (MOI) of 0.1, a multifocal cytopathic effect (CPE) developed. CPE was characterized by multinucleated cells and virus-specific intranuclear inclusions as determined by immunofluorescence and EM. In VZV- infected HB and HG cells only, large vacuoles were also seen in the cytoplasm of dying cells. Some vacuoles were almost devoid of structures. Within and at the limiting membranes of other vacuoles, aggregates of VZV particles (measuring 210--230 nm) were seen enveloped in osmiophilic material. VZV infection of HB and HG cultures was strongly cell-associated. Clarified tissue culture medium removed at maximum CPE failed to infect homologous HB or HG cells. When an inoculum of VZV-infected HB or HG cells was transferred to homologous uninfected cultures for 10--15 passages, the incubation period for CPE remained constant, and the titer of VZV in cells sampled randomly corresponded to the amount of virus that was used for original infection.", "contents": "Varicella-zoster virus infection of human brain cells and ganglion cells in tissue culture. The growth of varicella-zoster virus (VZV) in cultures of human brain (HB) and human ganglion (HG) cells was compared to VZV growth in human fibroblasts. Infected cultures were monitored by histologic, electron microscopic (EM), and virologic techniques. Two to three days after VZV infection of all cell cultures at a multiplicity of infection (MOI) of 0.1, a multifocal cytopathic effect (CPE) developed. CPE was characterized by multinucleated cells and virus-specific intranuclear inclusions as determined by immunofluorescence and EM. In VZV- infected HB and HG cells only, large vacuoles were also seen in the cytoplasm of dying cells. Some vacuoles were almost devoid of structures. Within and at the limiting membranes of other vacuoles, aggregates of VZV particles (measuring 210--230 nm) were seen enveloped in osmiophilic material. VZV infection of HB and HG cultures was strongly cell-associated. Clarified tissue culture medium removed at maximum CPE failed to infect homologous HB or HG cells. When an inoculum of VZV-infected HB or HG cells was transferred to homologous uninfected cultures for 10--15 passages, the incubation period for CPE remained constant, and the titer of VZV in cells sampled randomly corresponded to the amount of virus that was used for original infection."}
{"id": "PMID:204262", "title": "[Two outbreaks of \"Clostridium perfringens\" food poisoning: epidemiological remarks (author's transl)].", "content": "Two outbreaks of Cl. perfringens food poisoning which occurred in Florence during 1976 have been described. The first one involved three hundred primary school children; processed re-heated turkey meat was thought to have been the vehicle of infection in the school meal. The clinical symptoms consisted of mild diarrhoea in all cases and the duration of the illness was about 12 hours. The possible part played by food storage temperature, post-cooking periods and food trolleys in the spread of infection is discussed. The other outbreak interested three people who ate a dish with gravy in a restaurant; one of these suffered severe haemorrhagic enteritis and died after two weeks. Necroscopy was performed and the results of post-mortem examination as well as histological and bacteriological findings certified that the cause of death was severe enteritis (Necrotizing enteritis) in elderly debilitated patient (with diabetes, chronic bronchitis, arteriosclerosis and previously gastroresected).", "contents": "[Two outbreaks of \"Clostridium perfringens\" food poisoning: epidemiological remarks (author's transl)]. Two outbreaks of Cl. perfringens food poisoning which occurred in Florence during 1976 have been described. The first one involved three hundred primary school children; processed re-heated turkey meat was thought to have been the vehicle of infection in the school meal. The clinical symptoms consisted of mild diarrhoea in all cases and the duration of the illness was about 12 hours. The possible part played by food storage temperature, post-cooking periods and food trolleys in the spread of infection is discussed. The other outbreak interested three people who ate a dish with gravy in a restaurant; one of these suffered severe haemorrhagic enteritis and died after two weeks. Necroscopy was performed and the results of post-mortem examination as well as histological and bacteriological findings certified that the cause of death was severe enteritis (Necrotizing enteritis) in elderly debilitated patient (with diabetes, chronic bronchitis, arteriosclerosis and previously gastroresected)."}
{"id": "PMID:204268", "title": "Expression of \"early\" and \"late\" viral functions in a somatic cell hybrid between a mouse cell and a spontaneous yielder SV 40-transformed Chinese hamster cell.", "content": "A somatic cell hybrid (Cl. 6d) was originated from the fusion of mouse 3T3-4E) and spontaneous yielder SV 40-transformed Chinese hamster (CHK/SVLP AG) cells. During the early stages of its history, the C1. 6d hybrid underwent a rapid chromosome loss, preferentially loosing hamster chromosomes. This was not a constant tendency of the hybrid cells. As the parental CHK)SVLP AG cells, the hybrid cells were always found 100 per cent SV40 T-antigen positive. While CHK/SVLP AG cells infectious SV 40 DNA, V-antigen and virus were regularly detected, in the hybrid cells only infectious DNA was occasionally detected. This was not due either to the loww of an essential Chinese hamster gene(s) or to the presence of an inhibiting mouse cell component(s); it was apparently the consequence of inability of the cells to properly activate the resident SV 40 genome(s). After superinfection with SV 40 DNA, the hybrid cells-though capable of synthesizing SV 40 V-antigen--were unable to ensure virus assembly. Experimental evidence was obtained suggesting that SV 40 maturation is dependent of a cellular function(s).", "contents": "Expression of \"early\" and \"late\" viral functions in a somatic cell hybrid between a mouse cell and a spontaneous yielder SV 40-transformed Chinese hamster cell. A somatic cell hybrid (Cl. 6d) was originated from the fusion of mouse 3T3-4E) and spontaneous yielder SV 40-transformed Chinese hamster (CHK/SVLP AG) cells. During the early stages of its history, the C1. 6d hybrid underwent a rapid chromosome loss, preferentially loosing hamster chromosomes. This was not a constant tendency of the hybrid cells. As the parental CHK)SVLP AG cells, the hybrid cells were always found 100 per cent SV40 T-antigen positive. While CHK/SVLP AG cells infectious SV 40 DNA, V-antigen and virus were regularly detected, in the hybrid cells only infectious DNA was occasionally detected. This was not due either to the loww of an essential Chinese hamster gene(s) or to the presence of an inhibiting mouse cell component(s); it was apparently the consequence of inability of the cells to properly activate the resident SV 40 genome(s). After superinfection with SV 40 DNA, the hybrid cells-though capable of synthesizing SV 40 V-antigen--were unable to ensure virus assembly. Experimental evidence was obtained suggesting that SV 40 maturation is dependent of a cellular function(s)."}
{"id": "PMID:204269", "title": "Cytomegalovirus infection and graft survival in renal graft recipients.", "content": "We have studied 85 patients who received a renal transplant for CMV infection as well as for herpes simplex (HSV), herpes zoster (HZ), measles, mumps, rubella and hepatitis B. We found no evidence of primary or secondary infections for the non herpetic viruses except for hepatitis B infection that occurred in 17 per cent of the patients. CMV infection occurred in 87 per cent of the patients while antibody rises to HZ and HSV occurred in 30 and 13 per cent of the patients, respectively. The CMV infections occurred 2 to 4 months after the transplantation (mean time 11.1 weeks) and seemed to trigger the first episode of renal rejection that occurred earlier in the CMV infected group (mean time 12.1 weeks) than in the uninfected group (mean time 18.6 weeks). This difference in time is highly significant, p less than 0.001). However these CMV injections did not decrease the longterm survival of the grafted kidneys.", "contents": "Cytomegalovirus infection and graft survival in renal graft recipients. We have studied 85 patients who received a renal transplant for CMV infection as well as for herpes simplex (HSV), herpes zoster (HZ), measles, mumps, rubella and hepatitis B. We found no evidence of primary or secondary infections for the non herpetic viruses except for hepatitis B infection that occurred in 17 per cent of the patients. CMV infection occurred in 87 per cent of the patients while antibody rises to HZ and HSV occurred in 30 and 13 per cent of the patients, respectively. The CMV infections occurred 2 to 4 months after the transplantation (mean time 11.1 weeks) and seemed to trigger the first episode of renal rejection that occurred earlier in the CMV infected group (mean time 12.1 weeks) than in the uninfected group (mean time 18.6 weeks). This difference in time is highly significant, p less than 0.001). However these CMV injections did not decrease the longterm survival of the grafted kidneys."}
{"id": "PMID:204270", "title": "Inhibition of adsorption of West-Nile and herpes simplex viruses by procaine.", "content": "The effect of the local anaesthetic drug procaine on the adsorption of two enveloped viruses was studied. Physiological concentrations of the drug (7 X 10(-3)--7 X 10(-2) M) strongly inhibited the adsorption of both West-Nile and herpes viruses as determined by plaque assay and the infective center assay.", "contents": "Inhibition of adsorption of West-Nile and herpes simplex viruses by procaine. The effect of the local anaesthetic drug procaine on the adsorption of two enveloped viruses was studied. Physiological concentrations of the drug (7 X 10(-3)--7 X 10(-2) M) strongly inhibited the adsorption of both West-Nile and herpes viruses as determined by plaque assay and the infective center assay."}
{"id": "PMID:204271", "title": "Identification and study of a poxvirus isolated from wild rodents in Turkmenia.", "content": "A new poxvirus was isolated in 1974 from the kidney of a wild big gerbil (Rhombomys opimus) caught in Turkmenia, where these gerbils are wide-spread. The virus resembles cowpox virus and is markedly different from the virus of infectious ectromelia, the best-known poxvirus of rodents. The new virus is apparently identical to other poxvirus isolates made from white rats and Felidae in the Moscow Zoo. Experimental inoculation of the natural hosts--big gerbils and yellow susliks (Citellus fulvus)--produced a severe infection with a high mortality rate. Trnasmission of virus to uninoculated cage mates was shown to occur. Virus persisted in convalescent animals and was present in urine 3 weeks after inoculation and in kidney and testis for at least 5 weeks after inoculation. The role of rodents as natural hosts of poxviruses is discussed.", "contents": "Identification and study of a poxvirus isolated from wild rodents in Turkmenia. A new poxvirus was isolated in 1974 from the kidney of a wild big gerbil (Rhombomys opimus) caught in Turkmenia, where these gerbils are wide-spread. The virus resembles cowpox virus and is markedly different from the virus of infectious ectromelia, the best-known poxvirus of rodents. The new virus is apparently identical to other poxvirus isolates made from white rats and Felidae in the Moscow Zoo. Experimental inoculation of the natural hosts--big gerbils and yellow susliks (Citellus fulvus)--produced a severe infection with a high mortality rate. Trnasmission of virus to uninoculated cage mates was shown to occur. Virus persisted in convalescent animals and was present in urine 3 weeks after inoculation and in kidney and testis for at least 5 weeks after inoculation. The role of rodents as natural hosts of poxviruses is discussed."}
{"id": "PMID:204272", "title": "Biochemical Transformation of mouse cells by herpes simplex virus types 1 and 2: comparison of different methods for inactivation of viruses.", "content": "Comparison of methods to inactivate lytic properties of herpes simplex viruses revealed that ultraviolet irradiation, photodynamic procedures, and heat all destroyed infectivity effectively. Ability to biochemically transform thymidine kinase deficient cells to an enzyme positive phenotype was retained after limited exposure to heat or ultraviolet light but appeared to be destroyed by photodynamic methods employing neutral red. Exposure to 56 degrees C quickly and effectively destroyed transforming activity with lower temperatures being less effective. The most reproducible transforming assays were obtained following inactivation by ultraviolet light. Cell cultures developed by this procedure were virus-free but retained ability to synthesize virus-specific antigens.", "contents": "Biochemical Transformation of mouse cells by herpes simplex virus types 1 and 2: comparison of different methods for inactivation of viruses. Comparison of methods to inactivate lytic properties of herpes simplex viruses revealed that ultraviolet irradiation, photodynamic procedures, and heat all destroyed infectivity effectively. Ability to biochemically transform thymidine kinase deficient cells to an enzyme positive phenotype was retained after limited exposure to heat or ultraviolet light but appeared to be destroyed by photodynamic methods employing neutral red. Exposure to 56 degrees C quickly and effectively destroyed transforming activity with lower temperatures being less effective. The most reproducible transforming assays were obtained following inactivation by ultraviolet light. Cell cultures developed by this procedure were virus-free but retained ability to synthesize virus-specific antigens."}
{"id": "PMID:204273", "title": "Herpes simplex retinitis.", "content": "Fatal encephalitis with accompanying retinitis developed in a previously healthy 18-month-old infant. Clinically the disease appeared as whitish-yellow punctate lesions, perivascular cuffing, and hemorrhage. The antibody titer to herpes simplex rose from 1:8 on the day of admission to 1:256 on the day of death. Postmortem, intranuclear inclusion bodies that were typical of those found with herpesvirus were seen in the brain and retina. Viral particles consistent with those of herpesvirus were found by electron microscopy in the brain and in the inner-nuclear and ganglion-nerve fiber layers of the retina. This demonstrates the direct infectious nature of herpetic retinitis. Hematogenous spread of the virus to the retina is presumed.", "contents": "Herpes simplex retinitis. Fatal encephalitis with accompanying retinitis developed in a previously healthy 18-month-old infant. Clinically the disease appeared as whitish-yellow punctate lesions, perivascular cuffing, and hemorrhage. The antibody titer to herpes simplex rose from 1:8 on the day of admission to 1:256 on the day of death. Postmortem, intranuclear inclusion bodies that were typical of those found with herpesvirus were seen in the brain and retina. Viral particles consistent with those of herpesvirus were found by electron microscopy in the brain and in the inner-nuclear and ganglion-nerve fiber layers of the retina. This demonstrates the direct infectious nature of herpetic retinitis. Hematogenous spread of the virus to the retina is presumed."}
{"id": "PMID:204274", "title": "Oat-cell carcinoma of the larynx.", "content": "The diagnoses of three cases of laryngeal oat-cell carcinoma were confirmed by electron microscopy. As in pulmonary oat-cell carcinoma, the prognosis in these cases is poor; of our three cases and the previously reported cases of this tumor type in the larynx, all but one of the patients, for whom there is adequate follow-up information, have died of widespread metastases. Aggressive radiation therapy and systemic chemotherapy appear indicated if improved survival is to be achieved.", "contents": "Oat-cell carcinoma of the larynx. The diagnoses of three cases of laryngeal oat-cell carcinoma were confirmed by electron microscopy. As in pulmonary oat-cell carcinoma, the prognosis in these cases is poor; of our three cases and the previously reported cases of this tumor type in the larynx, all but one of the patients, for whom there is adequate follow-up information, have died of widespread metastases. Aggressive radiation therapy and systemic chemotherapy appear indicated if improved survival is to be achieved."}
{"id": "PMID:204275", "title": "Histopathology of a rhinotracheitis of turkey poults associated with adenoviruses.", "content": "Tissues from turkey poults with adenovirus-associated respiratory disease were examined for microscopic lesions. Histopathologic changes observed in tissue from poults submitted with clinical signs of severe respiratory disease ranged from an acute mucoid rhinotracheitis through a fibrinonecrotic tracheitis to a chronic polypoid tracheitis with squamous metaplasia of the tracheal epithelium. Clinically normal poults housed with poults that subsequently developed clinical signs of the disease rarely had basophilic intranuclear inclusions within the epithelial cells of nasal turbinates.", "contents": "Histopathology of a rhinotracheitis of turkey poults associated with adenoviruses. Tissues from turkey poults with adenovirus-associated respiratory disease were examined for microscopic lesions. Histopathologic changes observed in tissue from poults submitted with clinical signs of severe respiratory disease ranged from an acute mucoid rhinotracheitis through a fibrinonecrotic tracheitis to a chronic polypoid tracheitis with squamous metaplasia of the tracheal epithelium. Clinically normal poults housed with poults that subsequently developed clinical signs of the disease rarely had basophilic intranuclear inclusions within the epithelial cells of nasal turbinates."}
{"id": "PMID:204276", "title": "An in vivo and in vitro study of infectious laryngotracheitis virus in chicken leukocytes.", "content": "Infectious laryngotracheitis (ILT) virus, an avian herpesvirus, caused an infection in chickens that was followed by leukopenia due to a decrease in the number of circulating lymphocytes. Viral synthesis in leukocytes in cell cultures was evident by specific and progressive viral antigens in the nuclei of infected leukocytes as shown by fluorescent-antibody technique and by the formation of multinucleated giant cells, typical of the herpesviruses. In addition, viral multiplication was observed in the leukocyte cell cultures as shown by viral assay. It is suggested that the leukocytes in chicken are participating in the production of ILT virus by serving as host cells for viral multiplication. This is followed by a cytopathogenic effect, with the production of multinucleated giant cells. That may result in the destruction of cells, causing a leukopenia.", "contents": "An in vivo and in vitro study of infectious laryngotracheitis virus in chicken leukocytes. Infectious laryngotracheitis (ILT) virus, an avian herpesvirus, caused an infection in chickens that was followed by leukopenia due to a decrease in the number of circulating lymphocytes. Viral synthesis in leukocytes in cell cultures was evident by specific and progressive viral antigens in the nuclei of infected leukocytes as shown by fluorescent-antibody technique and by the formation of multinucleated giant cells, typical of the herpesviruses. In addition, viral multiplication was observed in the leukocyte cell cultures as shown by viral assay. It is suggested that the leukocytes in chicken are participating in the production of ILT virus by serving as host cells for viral multiplication. This is followed by a cytopathogenic effect, with the production of multinucleated giant cells. That may result in the destruction of cells, causing a leukopenia."}
{"id": "PMID:204277", "title": "Dual virus maturation of both pathogenic and apathogenic Marek's disease herpesvirus (MDHV) in the feather follicles of dually infected chickens.", "content": "Infectious cell-free viruses of both pathogenic and apathogenic Marek's disease herpesvirus (MDHV) were detected in feather-tip extracts of chickens dually infected with both MDHV isolants either by inoculation or by contact exposure. This indicated concurrent viral maturation of both pathogenic and apathogenic MDHV isolants in the feather-follicle epithelium, resulting in possible double shedding of the two isolants.", "contents": "Dual virus maturation of both pathogenic and apathogenic Marek's disease herpesvirus (MDHV) in the feather follicles of dually infected chickens. Infectious cell-free viruses of both pathogenic and apathogenic Marek's disease herpesvirus (MDHV) were detected in feather-tip extracts of chickens dually infected with both MDHV isolants either by inoculation or by contact exposure. This indicated concurrent viral maturation of both pathogenic and apathogenic MDHV isolants in the feather-follicle epithelium, resulting in possible double shedding of the two isolants."}
{"id": "PMID:204278", "title": "Physicochemical characterization and pathogenicity studies of two turkey adenovirus isolants.", "content": "Two turkey adenoviruses were isolated from poults with respiratory disease, and their physicochemical properties were studied. The virus particles were unenveloped. contained DNA genome, replicated within the nuclei of infected cells, and were icosahedral in shape. Pathogenicity studies in poults indicated that North Carolina Kennedy isolant was a pathogen of relatively low virulence whereas the North Carolina Jackson isolant was nonpathogenic in commercial turkey poults.", "contents": "Physicochemical characterization and pathogenicity studies of two turkey adenovirus isolants. Two turkey adenoviruses were isolated from poults with respiratory disease, and their physicochemical properties were studied. The virus particles were unenveloped. contained DNA genome, replicated within the nuclei of infected cells, and were icosahedral in shape. Pathogenicity studies in poults indicated that North Carolina Kennedy isolant was a pathogen of relatively low virulence whereas the North Carolina Jackson isolant was nonpathogenic in commercial turkey poults."}
{"id": "PMID:204280", "title": "Antigenic analysis of several turkey respiratory adenoviruses by reciprocal-neutralization kinetics.", "content": "Five turkey adenoviruses were classified into four serologic groups by reciprocal-neutralization kinetics. Two viruses were found to be serologically homologous, while three others were found to be heterologous and placed in separate serologic groups.", "contents": "Antigenic analysis of several turkey respiratory adenoviruses by reciprocal-neutralization kinetics. Five turkey adenoviruses were classified into four serologic groups by reciprocal-neutralization kinetics. Two viruses were found to be serologically homologous, while three others were found to be heterologous and placed in separate serologic groups."}
{"id": "PMID:204279", "title": "Further studies on the classification of fowl adenoviruses.", "content": "In addition to the 8 fowl adenovirus serotypes described previously, 3 new serotypes were recognized. Two, A-2 and C2-B, were isolated in the U.S.A., and one, 380, in Northern Ireland. In addition another isolate, X-11, has a broader antigenicity than YR-36 and therefore should be used instead of YR-36 as prototype strain. It is concluded that there are at least 11 distinct fowl adenovirus serotypes on the basis of the serum-neutralization test.", "contents": "Further studies on the classification of fowl adenoviruses. In addition to the 8 fowl adenovirus serotypes described previously, 3 new serotypes were recognized. Two, A-2 and C2-B, were isolated in the U.S.A., and one, 380, in Northern Ireland. In addition another isolate, X-11, has a broader antigenicity than YR-36 and therefore should be used instead of YR-36 as prototype strain. It is concluded that there are at least 11 distinct fowl adenovirus serotypes on the basis of the serum-neutralization test."}
{"id": "PMID:204281", "title": "Complement-fixation test for reticuloendotheliosis viruses: limits of sensitivity in infected avian cells.", "content": "A specific micro-complement-fixation procedure for assay of avian reticuloendotheliosis viruses (REV), designated by use as the COFAR test, was compared with an assay based on immunofluorescent (IF) antibody staining of infected chick embryo fibroblasts. Endpoint titrations in which REV strain T, chick syncytial virus, and spleen necrosis virus were used indicated that cultures infected with limiting dilutions of each strain were positive by both procedures within 6 days. Depending on cell density, infection of 2 to 9% of the cells cultured produced an unambiguous positive response (titer greater than or equal to 1:2) with COFAR test. When both tests were used in a study on the transmission and in vivo status of ducks infected with spleen necrosis virus, COFAR was no less, possibly more, sensitive than IF for detecting infection in cultures inoculated with plasma.", "contents": "Complement-fixation test for reticuloendotheliosis viruses: limits of sensitivity in infected avian cells. A specific micro-complement-fixation procedure for assay of avian reticuloendotheliosis viruses (REV), designated by use as the COFAR test, was compared with an assay based on immunofluorescent (IF) antibody staining of infected chick embryo fibroblasts. Endpoint titrations in which REV strain T, chick syncytial virus, and spleen necrosis virus were used indicated that cultures infected with limiting dilutions of each strain were positive by both procedures within 6 days. Depending on cell density, infection of 2 to 9% of the cells cultured produced an unambiguous positive response (titer greater than or equal to 1:2) with COFAR test. When both tests were used in a study on the transmission and in vivo status of ducks infected with spleen necrosis virus, COFAR was no less, possibly more, sensitive than IF for detecting infection in cultures inoculated with plasma."}
{"id": "PMID:204285", "title": "Modifications of major aspects of myocardial ribonucleic acid metabolism as a response to noradrenaline. Behaviour of polyadenylate polymerase and ribonucleic acid polymerase, acetylation of histones and rate of synthesis of polyamines.", "content": "Noradrenaline added to perfused rabbit heart previously perfused with labelled precursors causes, after 2.5 and 5.0 min, a general increase of specific radioactivity or RNA in subcellular fractions, but no augmentation of acetylation of F2a2 and F2a1 histone fractions and no stimulation of DNA-dependent RNA polymerase activities. Synthesis of spermidine and spermine is enhanced at 10.0 min of treatment, when there is also a fall in specific radioactivity of RNA. The cytoplasmic Mn2+-stimulated polyadenylate polymerase activity is strongly enhanced 30s to 2.5 min after injection of noradrenaline or of dibutyryl cyclic AMP. Both the cyclic nucleotide and noradrenaline have no influence in vitro on the polyadenylate polymerase reaction.", "contents": "Modifications of major aspects of myocardial ribonucleic acid metabolism as a response to noradrenaline. Behaviour of polyadenylate polymerase and ribonucleic acid polymerase, acetylation of histones and rate of synthesis of polyamines. Noradrenaline added to perfused rabbit heart previously perfused with labelled precursors causes, after 2.5 and 5.0 min, a general increase of specific radioactivity or RNA in subcellular fractions, but no augmentation of acetylation of F2a2 and F2a1 histone fractions and no stimulation of DNA-dependent RNA polymerase activities. Synthesis of spermidine and spermine is enhanced at 10.0 min of treatment, when there is also a fall in specific radioactivity of RNA. The cytoplasmic Mn2+-stimulated polyadenylate polymerase activity is strongly enhanced 30s to 2.5 min after injection of noradrenaline or of dibutyryl cyclic AMP. Both the cyclic nucleotide and noradrenaline have no influence in vitro on the polyadenylate polymerase reaction."}
{"id": "PMID:204282", "title": "Influence of infectious bursal disease on the development of immunity to Eimeria tenella.", "content": "Specific-pathogen-free (SPF) chicks infected with infectious bursal disease (IBDV) virus at one day of age or midway (7 days) through a two-week immunization program for Eimeria tenella showed significantly less (P less than or equal to 0.05) protection against coccidal challenge as measured by lesion scores than chicks given IBDV after 14 days of coccidial immunization. The chicks showed complete protection to later coccidial challenge administered on Day 21. Bursae were markedly smaller from IBDV-infected chicks than from uninfected controls, and pathological changes were extensive. Virus-neutralization tests demonstrated that titers to IBD were higher in chicks exposed to the virus than in unexposed controls.", "contents": "Influence of infectious bursal disease on the development of immunity to Eimeria tenella. Specific-pathogen-free (SPF) chicks infected with infectious bursal disease (IBDV) virus at one day of age or midway (7 days) through a two-week immunization program for Eimeria tenella showed significantly less (P less than or equal to 0.05) protection against coccidal challenge as measured by lesion scores than chicks given IBDV after 14 days of coccidial immunization. The chicks showed complete protection to later coccidial challenge administered on Day 21. Bursae were markedly smaller from IBDV-infected chicks than from uninfected controls, and pathological changes were extensive. Virus-neutralization tests demonstrated that titers to IBD were higher in chicks exposed to the virus than in unexposed controls."}
{"id": "PMID:204286", "title": "The role of nucleoside diphosphatase in a uridine nucleotide cycle associated with lactose synthesis in rat mammary-gland Golgi apparatus.", "content": "1. UDP-galactose utilization by isolated Golgi vesicles or rat mammary gland synthesizing lactose causes accumulation of UMP but not UDP, although UDP is the immediate product of lactose synthase (EC 2.4.1.22). 2. This can be ascribed to a nucleoside diphosphatase (EC 3.6.1.6), specific for UDP, GDP and IDP, activated by bivalent metal ions and apparently located on the luminal face of the Golgi membrane. 3. The uridine diphosphatase activity exceeds the total galactosyltransferase activity 5-fold, and is estimated to maintain UDP at about 14 micrometer within the Golgi lumen. 4. Evidence is given that UMP, but not UDP, penetrates the membrane and that UMP is rephosphorylated to UDP by a UMP kinase located in the cytosol. 5. Golgi-cytosol relationships with respect to lactose synthesis are formulated in terms of a uridine nucleotide cycle which throws new light on the energy cost and possible regulation of lactose synthesis.", "contents": "The role of nucleoside diphosphatase in a uridine nucleotide cycle associated with lactose synthesis in rat mammary-gland Golgi apparatus. 1. UDP-galactose utilization by isolated Golgi vesicles or rat mammary gland synthesizing lactose causes accumulation of UMP but not UDP, although UDP is the immediate product of lactose synthase (EC 2.4.1.22). 2. This can be ascribed to a nucleoside diphosphatase (EC 3.6.1.6), specific for UDP, GDP and IDP, activated by bivalent metal ions and apparently located on the luminal face of the Golgi membrane. 3. The uridine diphosphatase activity exceeds the total galactosyltransferase activity 5-fold, and is estimated to maintain UDP at about 14 micrometer within the Golgi lumen. 4. Evidence is given that UMP, but not UDP, penetrates the membrane and that UMP is rephosphorylated to UDP by a UMP kinase located in the cytosol. 5. Golgi-cytosol relationships with respect to lactose synthesis are formulated in terms of a uridine nucleotide cycle which throws new light on the energy cost and possible regulation of lactose synthesis."}
{"id": "PMID:204284", "title": "Functional behaviour of isolated heart muscle mitochondria after in situ ischemia. Polarographic analysis of mitochondrial oxidative phosphorylation.", "content": "Heart muscle mitochondria with satisfactory functional parameters of oxidative phosphorylation and with morphologically intact structure were isolated from canine myocardium employing a modified KEA-medium (0.18 M KCl, 10 mM EDTA, 0.5% bovine serum albumin, pH 7.1) according to Sordahl and Schwartz (1). The functional behaviour of mitochondria was investigated after different durations of in situ ischemia (cardioplegia, 15 degrees C) and correlated with metabolic findings. During ischemia the following changes were seen: 1. Successive reduction of electron flow. 2. Relatively small impairment of phosphorylation efficiency. 3. Less damage of FAD- than NAD-catalyzed oxidative phosphorylation. 4. A marked increase of electron flow and thus recovery of phosphorylation rate even after longer ischemic periods by addition of cytochrome c. As important factors of accelerating mitochondrial impairment during ischemia the myocardial ATP decrease, the lactate and H+-activity increase are discussed.", "contents": "Functional behaviour of isolated heart muscle mitochondria after in situ ischemia. Polarographic analysis of mitochondrial oxidative phosphorylation. Heart muscle mitochondria with satisfactory functional parameters of oxidative phosphorylation and with morphologically intact structure were isolated from canine myocardium employing a modified KEA-medium (0.18 M KCl, 10 mM EDTA, 0.5% bovine serum albumin, pH 7.1) according to Sordahl and Schwartz (1). The functional behaviour of mitochondria was investigated after different durations of in situ ischemia (cardioplegia, 15 degrees C) and correlated with metabolic findings. During ischemia the following changes were seen: 1. Successive reduction of electron flow. 2. Relatively small impairment of phosphorylation efficiency. 3. Less damage of FAD- than NAD-catalyzed oxidative phosphorylation. 4. A marked increase of electron flow and thus recovery of phosphorylation rate even after longer ischemic periods by addition of cytochrome c. As important factors of accelerating mitochondrial impairment during ischemia the myocardial ATP decrease, the lactate and H+-activity increase are discussed."}
{"id": "PMID:204287", "title": "The uptake and release of calcium by heart mitochondria.", "content": "The kinetics of uptake of Ca(2+) by rat heart mitochondria were studied by a spectrophotometric method with Arsenazo III indicator. The exponential rate coefficients measured with or without added phosphate increase with the amount of Ca(2+) added up to about 24mum. Evidence is given that the effect is attributable to a combination of formation of chelates at low concentrations to act as Ca(2+) buffers, with co-transport of substrate to provide more respiratory fuel. The inhibitory effect of Mg(2+) depends on the Ca(2+) concentration, so with a constant [Mg(2+)] the low concentrations of Ca(2+) are most inhibited, and the rate coefficients are still more Ca(2+)-dependent. Ca(2+) uptake is slowed by local anaesthetics such as butacaine and dibucaine, and also by propranolol and palmitoyl-CoA. After an uptake, the release of Ca(2+) was investigated. The spontaneous release involves an initially slow and small appearance of free Ca(2+) and is followed by an auto-accelerated phase. The release is accompanied by a gradual decrease in internal ATP; it is initiated by palmitoyl-CoA (reversed by carnitine), by lysophosphatidylcholine, by Na(+) salts (reversed by oligomycin) and by K(+) salts added to a K(+)-free medium containing valinomycin. The process is probably a response to an increased energy load imposed on the mitochondria by the various conditions, which include the spontaneous action of phospholipase activated by traces of Ca(2+). The problem of how much mitochondrial activity is participating in normal heart Ca(2+) turnover is discussed, and experiments showing only 7-14% exchange of the mitochondrial Ca(2+) occurring in vivo in 10 or 20min are reported.", "contents": "The uptake and release of calcium by heart mitochondria. The kinetics of uptake of Ca(2+) by rat heart mitochondria were studied by a spectrophotometric method with Arsenazo III indicator. The exponential rate coefficients measured with or without added phosphate increase with the amount of Ca(2+) added up to about 24mum. Evidence is given that the effect is attributable to a combination of formation of chelates at low concentrations to act as Ca(2+) buffers, with co-transport of substrate to provide more respiratory fuel. The inhibitory effect of Mg(2+) depends on the Ca(2+) concentration, so with a constant [Mg(2+)] the low concentrations of Ca(2+) are most inhibited, and the rate coefficients are still more Ca(2+)-dependent. Ca(2+) uptake is slowed by local anaesthetics such as butacaine and dibucaine, and also by propranolol and palmitoyl-CoA. After an uptake, the release of Ca(2+) was investigated. The spontaneous release involves an initially slow and small appearance of free Ca(2+) and is followed by an auto-accelerated phase. The release is accompanied by a gradual decrease in internal ATP; it is initiated by palmitoyl-CoA (reversed by carnitine), by lysophosphatidylcholine, by Na(+) salts (reversed by oligomycin) and by K(+) salts added to a K(+)-free medium containing valinomycin. The process is probably a response to an increased energy load imposed on the mitochondria by the various conditions, which include the spontaneous action of phospholipase activated by traces of Ca(2+). The problem of how much mitochondrial activity is participating in normal heart Ca(2+) turnover is discussed, and experiments showing only 7-14% exchange of the mitochondrial Ca(2+) occurring in vivo in 10 or 20min are reported."}
{"id": "PMID:204288", "title": "Preparation of hepatic gap (communicating) junctions. Identification of the constituent polypeptide subunits.", "content": "1. Gap (communicating) junctions are plasma-membrane specializations of characteristic morphology that form transmembrane channels allowing direct communication between cells. Their preparation is described starting from mouse liver plasma membranes and the constituent polypeptides are deduced. 2. Gap junctions co-purify with collagen fibres when the plasma-membrane residues insoluble in N-dodecyl sarcosinate are fractionated on sucrose gradients. Sucrose-density perturbation by relipidation of isolated gap junctions or the use of urea to remove non-junctional membranes both failed to diminish the collagen content of fractions. 3. Removal of collagen by treatment with purified collagenase preparations yielded morphologically satisfactory gap-junction fractions. Analysis by polyacrylamide-gel electrophoresis of the polypeptides present in gap junctions prepared by procedures omitting or using collagenases indicated two non-glycosylated polypeptides, a major component of apparent mol.wt. 38000 and a minor 40000-mol.wt. component. These two polypeptides were also present in plasma membranes and the intermediate fractions. 4. Proteolysis of the gap-junction polypeptides yielding components of mol.wt. 34000, 25000 and below 20000 occurred when iodinated gap junctions were subject to prolonged collagenase treatment, thus explaining the variable polypeptide composition of gap junctions reported by others. 5. The morphological properties of the isolated gap junctions prepared by the various procedures are described.", "contents": "Preparation of hepatic gap (communicating) junctions. Identification of the constituent polypeptide subunits. 1. Gap (communicating) junctions are plasma-membrane specializations of characteristic morphology that form transmembrane channels allowing direct communication between cells. Their preparation is described starting from mouse liver plasma membranes and the constituent polypeptides are deduced. 2. Gap junctions co-purify with collagen fibres when the plasma-membrane residues insoluble in N-dodecyl sarcosinate are fractionated on sucrose gradients. Sucrose-density perturbation by relipidation of isolated gap junctions or the use of urea to remove non-junctional membranes both failed to diminish the collagen content of fractions. 3. Removal of collagen by treatment with purified collagenase preparations yielded morphologically satisfactory gap-junction fractions. Analysis by polyacrylamide-gel electrophoresis of the polypeptides present in gap junctions prepared by procedures omitting or using collagenases indicated two non-glycosylated polypeptides, a major component of apparent mol.wt. 38000 and a minor 40000-mol.wt. component. These two polypeptides were also present in plasma membranes and the intermediate fractions. 4. Proteolysis of the gap-junction polypeptides yielding components of mol.wt. 34000, 25000 and below 20000 occurred when iodinated gap junctions were subject to prolonged collagenase treatment, thus explaining the variable polypeptide composition of gap junctions reported by others. 5. The morphological properties of the isolated gap junctions prepared by the various procedures are described."}
{"id": "PMID:204289", "title": "Binding, interiorization and degradation of cholesteryl ester-labelled chylomicron-remmant particles by rat hepatocyte monolayers.", "content": "1. The cholesteryl ester of isolated chylomicron-remnant particles was efficiently degraded by hepatocyte monolayers. The degradation was sensitive to metabolic inhibitors. 2. With increasing amounts of remnant cholesteryl ester the rate of uptake approached saturation and conformed to a linear double-reciprocal plot. The V(max.) was determined as 80ng of cholesteryl ester/h per mg of protein and the apparent K(m) as 1.4mug of cholesteryl ester per mg of protein. The time course for the uptake and hydrolysis suggested that binding of particles to the cell surface preceded the degradation. 3. Cholesteryl esters of native chylomicrons were degraded to a much smaller extent and their presence had only a small inhibitory effect on the degradation of chylomicron remnants. Intestinal very-low-density lipoproteins were degraded somewhat faster than chylomicrons, and caused more inhibition of remnant degradation. Rat high-density lipoproteins inhibited the hydrolysis of remnant cholesteryl ester by up to 50%, but had less influence on the amount of cholesteryl ester that was bound to the cells. Serum decreased both the uptake and hydrolysis, whereas d=1.21 infranatant had no effect. 4. The cholesteryl ester hydrolysis after the uptake by the cells was inhibited by chloroquine and by colchicine. Only 28-36% of the unhydrolysed cholesteryl ester could be released from these cells by trypsin treatment, indicating that the major portion was truly intracellular. The particles that could be released from the cell surface by trypsin and those remaining in the medium had the same triacylglycerol/cholesteryl ester ratio as the added remnant particles. Significant amounts of denser particles were thus not formed during contact with the cell surface. 5. The presence of heparin, as well as preincubation of the cells with heparin, increased the uptake of chylomicron remnants. This effect was most marked in the presence of serum. A much smaller proportion of the other serum lipoproteins was taken up, and this proportion was not increased by heparin.", "contents": "Binding, interiorization and degradation of cholesteryl ester-labelled chylomicron-remmant particles by rat hepatocyte monolayers. 1. The cholesteryl ester of isolated chylomicron-remnant particles was efficiently degraded by hepatocyte monolayers. The degradation was sensitive to metabolic inhibitors. 2. With increasing amounts of remnant cholesteryl ester the rate of uptake approached saturation and conformed to a linear double-reciprocal plot. The V(max.) was determined as 80ng of cholesteryl ester/h per mg of protein and the apparent K(m) as 1.4mug of cholesteryl ester per mg of protein. The time course for the uptake and hydrolysis suggested that binding of particles to the cell surface preceded the degradation. 3. Cholesteryl esters of native chylomicrons were degraded to a much smaller extent and their presence had only a small inhibitory effect on the degradation of chylomicron remnants. Intestinal very-low-density lipoproteins were degraded somewhat faster than chylomicrons, and caused more inhibition of remnant degradation. Rat high-density lipoproteins inhibited the hydrolysis of remnant cholesteryl ester by up to 50%, but had less influence on the amount of cholesteryl ester that was bound to the cells. Serum decreased both the uptake and hydrolysis, whereas d=1.21 infranatant had no effect. 4. The cholesteryl ester hydrolysis after the uptake by the cells was inhibited by chloroquine and by colchicine. Only 28-36% of the unhydrolysed cholesteryl ester could be released from these cells by trypsin treatment, indicating that the major portion was truly intracellular. The particles that could be released from the cell surface by trypsin and those remaining in the medium had the same triacylglycerol/cholesteryl ester ratio as the added remnant particles. Significant amounts of denser particles were thus not formed during contact with the cell surface. 5. The presence of heparin, as well as preincubation of the cells with heparin, increased the uptake of chylomicron remnants. This effect was most marked in the presence of serum. A much smaller proportion of the other serum lipoproteins was taken up, and this proportion was not increased by heparin."}
{"id": "PMID:204290", "title": "Phosphorylation of pig brain microtubule proteins. General properties and partial characterization of endogenous substrate and cyclic AMP-dependent protein kinase.", "content": "1. A simple purification procedure for microtubule proteins is described, which involves a single assembly step in vitro in the absence of glycerol, followed by centrifugation through sucrose. 2. The preparation contains 80% tubulin (mol.wt. 54000), 15-20% of a 280000-mol.wt. protein and several other minor components of intermediate molecular weight after polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate and 2-mercaptoethanol. 3. In the presence of [gamma-32P]ATP, [32P]phosphate was incorporated into the 280000-mol.wt. component reaching half-maximal incorporation at 1-2 min, but no phosphorylation of tubulin was detected. Cyclic AMP (Km 0.8 micrometer) increased both the initial rate and the extent of incorporation of [32P]phosphate into this component. 4. About half of the endogenous protein kinase activity did not require cyclic AMP and was not inhibited by a heat-stable inhibitor protein from muscle. The remainder of the activity was cyclic AMP-dependent and sensitive to the inhibitor protein. A regulatory subunit was not dissociable from microtubules assembled in vitro in the presence of saturating concentrations of cyclic AMP. 5. The endogenous substrate and the endogenous protein kinase activity could be partially resolved chromatography on phosphocellulose. 6. The data show that cyclic AMP can moduate the activity of an endogenous protein kinase(s) with unusual properties and which phosphorylates a prominent microtubule-associated protein.", "contents": "Phosphorylation of pig brain microtubule proteins. General properties and partial characterization of endogenous substrate and cyclic AMP-dependent protein kinase. 1. A simple purification procedure for microtubule proteins is described, which involves a single assembly step in vitro in the absence of glycerol, followed by centrifugation through sucrose. 2. The preparation contains 80% tubulin (mol.wt. 54000), 15-20% of a 280000-mol.wt. protein and several other minor components of intermediate molecular weight after polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate and 2-mercaptoethanol. 3. In the presence of [gamma-32P]ATP, [32P]phosphate was incorporated into the 280000-mol.wt. component reaching half-maximal incorporation at 1-2 min, but no phosphorylation of tubulin was detected. Cyclic AMP (Km 0.8 micrometer) increased both the initial rate and the extent of incorporation of [32P]phosphate into this component. 4. About half of the endogenous protein kinase activity did not require cyclic AMP and was not inhibited by a heat-stable inhibitor protein from muscle. The remainder of the activity was cyclic AMP-dependent and sensitive to the inhibitor protein. A regulatory subunit was not dissociable from microtubules assembled in vitro in the presence of saturating concentrations of cyclic AMP. 5. The endogenous substrate and the endogenous protein kinase activity could be partially resolved chromatography on phosphocellulose. 6. The data show that cyclic AMP can moduate the activity of an endogenous protein kinase(s) with unusual properties and which phosphorylates a prominent microtubule-associated protein."}
{"id": "PMID:204291", "title": "The effect of streptozotocin-induced diabetes and of insulin supplementation on glycogen metabolism in rat liver.", "content": "The effects of streptozotocin-induced diabetes and of insulin supplementation to diabetic rats on glycogen-metabolizing enzymes in liver were determined. The results were compared with those from control animals. The activities of glycogenolytic enzymes, i.e. phosphorylase (both a and b), phosphorylase kinase and protein kinase (in the presence or in the absence of cyclic AMP), were significantly decreased in the diabetic animals. The enzyme activities were restored to control values by insulin therapy. Glycogen synthase (I-form) activity, similarly decreased in the diabetic animals, was also restored to control values after the administration of insulin. The increase in glycogen synthase(I-form) activity after insulin treatment was associated with a concomitant increase in phosphoprotein phosphatase activity. The increase in phosphatase activity was due to (i) a change in the activity of the enzyme itself and (ii) a decrease in a heat stable protein inhibitor of the phosphatase activity.", "contents": "The effect of streptozotocin-induced diabetes and of insulin supplementation on glycogen metabolism in rat liver. The effects of streptozotocin-induced diabetes and of insulin supplementation to diabetic rats on glycogen-metabolizing enzymes in liver were determined. The results were compared with those from control animals. The activities of glycogenolytic enzymes, i.e. phosphorylase (both a and b), phosphorylase kinase and protein kinase (in the presence or in the absence of cyclic AMP), were significantly decreased in the diabetic animals. The enzyme activities were restored to control values by insulin therapy. Glycogen synthase (I-form) activity, similarly decreased in the diabetic animals, was also restored to control values after the administration of insulin. The increase in glycogen synthase(I-form) activity after insulin treatment was associated with a concomitant increase in phosphoprotein phosphatase activity. The increase in phosphatase activity was due to (i) a change in the activity of the enzyme itself and (ii) a decrease in a heat stable protein inhibitor of the phosphatase activity."}
{"id": "PMID:204292", "title": "An arsenical analogue of adenosine diphosphate.", "content": "An analogue of ADP was made in which the terminal phosphono-oxy group, -O-PO(OH)2, has been replaced by the arsonomethyl group, -CH2-AsO(OH)2. This compound cannot form a stable analogue of ATP because anhydrides of arsonic acids are rapidly hydrolysed, so that any enzyme that phosphorylates ADP and accepts this analogue as a substrate should release orthophosphate in its presence. The analogue proves to be a poor substrate for 3-phosphoglycerate kinase (V/Km is diminished by a factor of 10(2)-10(3)) and a very poor substrate for pyruvate kinase (V/Km is diminished by a factor of 10(5)-10(6)). No substrate action was detected with adenyl kinase and creatine kinase.", "contents": "An arsenical analogue of adenosine diphosphate. An analogue of ADP was made in which the terminal phosphono-oxy group, -O-PO(OH)2, has been replaced by the arsonomethyl group, -CH2-AsO(OH)2. This compound cannot form a stable analogue of ATP because anhydrides of arsonic acids are rapidly hydrolysed, so that any enzyme that phosphorylates ADP and accepts this analogue as a substrate should release orthophosphate in its presence. The analogue proves to be a poor substrate for 3-phosphoglycerate kinase (V/Km is diminished by a factor of 10(2)-10(3)) and a very poor substrate for pyruvate kinase (V/Km is diminished by a factor of 10(5)-10(6)). No substrate action was detected with adenyl kinase and creatine kinase."}
{"id": "PMID:204293", "title": "Properties of cytochrome c modified by attachment to a carbohydrate polymer.", "content": "By enzymic digestion of the polysaccharide part of the covalent complex between cytochrome c and Sephadex G-200, a new water-soluble cytochrome c derivative is obtained (called cytochrome cr). Measurement of the free amino groups of this derivative indicates that on average the molar ratio between cytochrome c and polysaccharide is close to 1. Chemical determination of the sugar content gives a value of approx. 24000 for the molecular weight of cytochrome cr. On these bases the soluble cytochrome cr complex may be thought of as a folded protein to which a long polysaccharide tail is covalently bound. The functional behaviour of cytochrome cr is much more similar to that of the native molecule than to that of the insoluble complex (cytochrome ci). In particular the kinetics of the reaction of cytochrome cr and cytochrome cn (native) with ascorbate, ferrocyanide-ferricyanide, O2 and cytochrome c oxidase were investigated in considerable detail. The results of these experiments, together with the observation that the insoluble complex of cytochrome c is a very poor substrate of cytochrome c oxidase [Colosimo, Brunori & Antonini (1976) Biochem. J. 153, (657-661], indicate that hindrance effects constraining the approach between cytochrome cr and its oxidase are of greater importance than specific chemical modifications in determining the functional behavior of the protein.", "contents": "Properties of cytochrome c modified by attachment to a carbohydrate polymer. By enzymic digestion of the polysaccharide part of the covalent complex between cytochrome c and Sephadex G-200, a new water-soluble cytochrome c derivative is obtained (called cytochrome cr). Measurement of the free amino groups of this derivative indicates that on average the molar ratio between cytochrome c and polysaccharide is close to 1. Chemical determination of the sugar content gives a value of approx. 24000 for the molecular weight of cytochrome cr. On these bases the soluble cytochrome cr complex may be thought of as a folded protein to which a long polysaccharide tail is covalently bound. The functional behaviour of cytochrome cr is much more similar to that of the native molecule than to that of the insoluble complex (cytochrome ci). In particular the kinetics of the reaction of cytochrome cr and cytochrome cn (native) with ascorbate, ferrocyanide-ferricyanide, O2 and cytochrome c oxidase were investigated in considerable detail. The results of these experiments, together with the observation that the insoluble complex of cytochrome c is a very poor substrate of cytochrome c oxidase [Colosimo, Brunori & Antonini (1976) Biochem. J. 153, (657-661], indicate that hindrance effects constraining the approach between cytochrome cr and its oxidase are of greater importance than specific chemical modifications in determining the functional behavior of the protein."}
{"id": "PMID:204294", "title": "Purification, characterization and inhibition of human skin collagenase.", "content": "1. The neutral collagenase released into the culture medium by explants of human skin tissue was purified by ultrafiltration and column chromatography. The final enzyme preparation had a specific activity against thermally reconstituted collagen fibrils of 32mug of collagen degraded/min per mg of enzyme protein, representing a 266-fold increase over that of the culture medium. Electrophoresis in polyacrylamide disc gels showed it to migrate as a single protein band from which enzyme activity could be eluted. Chromatographic and polyacrylamide-gel-elution experiments provided no evidence for the existence of more than one active collagenase. 2. The molecular weight of the enzyme estimated from gel filtration and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis was approx. 60000. The purified collagenase, having a pH optimum of 7.5-8.5, did not hydrolyse the synthetic collagen peptide 4-phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-d-Arg-OH and had no non-specific proteinase activity when examined against non-collagenous proteins. 3. It attacked undenatured collagen in solution at 25 degrees C, producing the two characteristic products TC(A)((3/4)) and TC(B)((1/4)). Collagen types I, II and III were all cleaved in a similar manner by the enzyme at 25 degrees C, but under similar conditions basement-membrane collagen appeared not to be susceptible to collagenase attack. At 37 degrees C the enzyme attacked gelatin, producing initially three-quarter and one-quarter fragments of the alpha-chains, which were degraded further at a lower rate. As judged by the release of soluble hydroxyproline peptides and electron microscopy, the purified enzyme degraded insoluble collagen derived from human skin at 37 degrees C, but at a rate much lower than that for reconstituted collagen fibrils. 4. Inhibition of the skin collagenase was obtained with EDTA, 1,10-phenanthroline, cysteine, dithiothreitol and sodium aurothiomaleate. Cartilage proteoglycans did not inhibit the enzyme. The serum proteins alpha(2)-macroglobulin and beta(1)-anti-collagenase both inhibited the enzyme, but alpha(1)-anti-trypsin did not. 5. The physicochemical and enzymic properties of the skin enzyme are discussed in relation to those of other human collagenases.", "contents": "Purification, characterization and inhibition of human skin collagenase. 1. The neutral collagenase released into the culture medium by explants of human skin tissue was purified by ultrafiltration and column chromatography. The final enzyme preparation had a specific activity against thermally reconstituted collagen fibrils of 32mug of collagen degraded/min per mg of enzyme protein, representing a 266-fold increase over that of the culture medium. Electrophoresis in polyacrylamide disc gels showed it to migrate as a single protein band from which enzyme activity could be eluted. Chromatographic and polyacrylamide-gel-elution experiments provided no evidence for the existence of more than one active collagenase. 2. The molecular weight of the enzyme estimated from gel filtration and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis was approx. 60000. The purified collagenase, having a pH optimum of 7.5-8.5, did not hydrolyse the synthetic collagen peptide 4-phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-d-Arg-OH and had no non-specific proteinase activity when examined against non-collagenous proteins. 3. It attacked undenatured collagen in solution at 25 degrees C, producing the two characteristic products TC(A)((3/4)) and TC(B)((1/4)). Collagen types I, II and III were all cleaved in a similar manner by the enzyme at 25 degrees C, but under similar conditions basement-membrane collagen appeared not to be susceptible to collagenase attack. At 37 degrees C the enzyme attacked gelatin, producing initially three-quarter and one-quarter fragments of the alpha-chains, which were degraded further at a lower rate. As judged by the release of soluble hydroxyproline peptides and electron microscopy, the purified enzyme degraded insoluble collagen derived from human skin at 37 degrees C, but at a rate much lower than that for reconstituted collagen fibrils. 4. Inhibition of the skin collagenase was obtained with EDTA, 1,10-phenanthroline, cysteine, dithiothreitol and sodium aurothiomaleate. Cartilage proteoglycans did not inhibit the enzyme. The serum proteins alpha(2)-macroglobulin and beta(1)-anti-collagenase both inhibited the enzyme, but alpha(1)-anti-trypsin did not. 5. The physicochemical and enzymic properties of the skin enzyme are discussed in relation to those of other human collagenases."}
{"id": "PMID:204295", "title": "Uridine diphosphate glucose-sterol glucosyltransferase and nucleoside diphosphatase activities in etiolated pea seedlings.", "content": "1. UDP-glucose-sterol glucosyltransferase and nucleoside diphosphatases were isolated in a particulate fraction from 7-day-old etiolated pea seedlings. The glucosyltransferase and UDPase (uridine diphosphatase) are stimulated by Ca2+ cation, less so by Mg2+ cation, and inhibited by Zn2+. 2. Each activity has a pH optimum near 8. 3. The glucosyltransferase is specific for UDP-glucose as the glucosyl donor and is inhibited by UDP. Partial recovery from UDP inhibition is effected by preincubation of the enzyme. 4. Freeze-thaw treatment and subsequent sucrose-density-gradient centrifugation of the particulate fraction shows the glucosyltransferase to be widely distributed among cell fractions but to be most active in particles with a density of 1.15 g/ml. UDPase is most active in particulate material with a density of over 1.18 g/ml but an activity peak also appears at 1.15 g/ml. Of several nucleoside diphosphatase activities, UDPase activity is most enhanced by the freeze-thaw and sucrose-density-gradient-fractionation procedures. 5. Detergent treatment with 0.1% sodium deoxycholate allows the partial solubilization of the glucosyltransferase and UDPase. The two activities are similarly distributed between pellet and supernatant after high-speed centrifugation for two different time intervals. 6. A role for UDPase in the functioning of glucosylation reactions is discussed.", "contents": "Uridine diphosphate glucose-sterol glucosyltransferase and nucleoside diphosphatase activities in etiolated pea seedlings. 1. UDP-glucose-sterol glucosyltransferase and nucleoside diphosphatases were isolated in a particulate fraction from 7-day-old etiolated pea seedlings. The glucosyltransferase and UDPase (uridine diphosphatase) are stimulated by Ca2+ cation, less so by Mg2+ cation, and inhibited by Zn2+. 2. Each activity has a pH optimum near 8. 3. The glucosyltransferase is specific for UDP-glucose as the glucosyl donor and is inhibited by UDP. Partial recovery from UDP inhibition is effected by preincubation of the enzyme. 4. Freeze-thaw treatment and subsequent sucrose-density-gradient centrifugation of the particulate fraction shows the glucosyltransferase to be widely distributed among cell fractions but to be most active in particles with a density of 1.15 g/ml. UDPase is most active in particulate material with a density of over 1.18 g/ml but an activity peak also appears at 1.15 g/ml. Of several nucleoside diphosphatase activities, UDPase activity is most enhanced by the freeze-thaw and sucrose-density-gradient-fractionation procedures. 5. Detergent treatment with 0.1% sodium deoxycholate allows the partial solubilization of the glucosyltransferase and UDPase. The two activities are similarly distributed between pellet and supernatant after high-speed centrifugation for two different time intervals. 6. A role for UDPase in the functioning of glucosylation reactions is discussed."}
{"id": "PMID:204296", "title": "Protein-lipid interactions in cytochrome oxidase from Saccharomyces cerevisiae. Effects of detergents and reconstitution of enzyme activity by phospholipids by using cholate-mediated exchange.", "content": "Cytochrome oxidase, purified from the yeast Saccharomyces cerevisiae, was shown to have associated phospholipid, cholate or detergent, which could be varied by dialysis or (NH4)2SO4 precipitation of the protein. Cholate and the detergents Triton X-100 and Tween 80 were shown to differ in their ability to support enzyme activity. Changes in the Vmax, but not the Km, for ferrocytochrome c as the cholate concentration was varied indicate that cholate increases the number of exposed active sites of the enzyme. Cholate was used to introduce chosen phospholipids into the lipid environment of yeast cytochrome oxidase. Kinetic studies clearly showed that cholate can mediate exchange of exogenous for endogenous phospholipid. All phospholipids screened supported activity up to the basal value for the unsubstituted enzyme, whereas mitochondrial phosphatidylethanolamine and various phosphatidlycholines (except 1,2-dipalmitoyl-sn-glycero-3-phosphocholine) produced enhanced activity. A detailed kinetic examination revealed that the major effect of phosphatidylethanolamine is to increase k+1, whereas the major effect of phosphatidylcholine is to increase K+2 in the minimal kinetic scheme E + S k+1 in equilibrium k-1 ES k+2 leads to E + P Cardiolipin, although supporting activity, does not give any enhancement of k+1 or k+2 over the values for the cholate control. The relevance of these observations to protein-lipid interactions in cytochrome oxidase is discussed.", "contents": "Protein-lipid interactions in cytochrome oxidase from Saccharomyces cerevisiae. Effects of detergents and reconstitution of enzyme activity by phospholipids by using cholate-mediated exchange. Cytochrome oxidase, purified from the yeast Saccharomyces cerevisiae, was shown to have associated phospholipid, cholate or detergent, which could be varied by dialysis or (NH4)2SO4 precipitation of the protein. Cholate and the detergents Triton X-100 and Tween 80 were shown to differ in their ability to support enzyme activity. Changes in the Vmax, but not the Km, for ferrocytochrome c as the cholate concentration was varied indicate that cholate increases the number of exposed active sites of the enzyme. Cholate was used to introduce chosen phospholipids into the lipid environment of yeast cytochrome oxidase. Kinetic studies clearly showed that cholate can mediate exchange of exogenous for endogenous phospholipid. All phospholipids screened supported activity up to the basal value for the unsubstituted enzyme, whereas mitochondrial phosphatidylethanolamine and various phosphatidlycholines (except 1,2-dipalmitoyl-sn-glycero-3-phosphocholine) produced enhanced activity. A detailed kinetic examination revealed that the major effect of phosphatidylethanolamine is to increase k+1, whereas the major effect of phosphatidylcholine is to increase K+2 in the minimal kinetic scheme E + S k+1 in equilibrium k-1 ES k+2 leads to E + P Cardiolipin, although supporting activity, does not give any enhancement of k+1 or k+2 over the values for the cholate control. The relevance of these observations to protein-lipid interactions in cytochrome oxidase is discussed."}
{"id": "PMID:204297", "title": "Participation of the iron-sulphur cluster and of the covalently bound coenzyme of trimethylamine dehydrogenase in catalysis.", "content": "Bacterial trimethylamine dehydrogenase contains a novel type of covalently bound flavin mononucleotide and a tetrameric iron-sulphur centre. The dehydrogenase takes up 1.5mol of dithionite/mol of enzyme and is thereby converted into the flavin quinol-reduced (4Fe-4S) form, with the expected bleaching of the visible absorption band of the flavin and the emergence of signals of typical reduced ferredoxin in the electronparamagnetic-resonance spectrum. On reduction with a slight excess of substrate, however, unusual absorption and electron-paramagnetic-resonance spectra appear quite rapidly. The latter is attributed to extensive interaction between the reduced (4Fe-4S) centre and the flavin semiquinone. The species of enzyme arising during the catalytic cycle were studied by a combination of rapid-freeze e.p.r. and stopped-flow spectophotometry. The initial reduction of the flavin to the quinol form is far too rapid to be rate-limiting in catalysis, as is the reoxidation of the substrate-reduced enzyme by phenazine methosulphate. Formation of the spin-spin-interacting species from the dihydroflavin is considerably slower, however, and it may be the rate-limiting step in the catalytic cycle, since its rate of formation agrees reasonably well with the catalytic-centre activity determined in steady-state kinetic assays. In addition to the interacting form, a second form of the enzyme was noted during reduction by trimethylamine, differing in absorption spectrum, the structure of which remains to be determined.", "contents": "Participation of the iron-sulphur cluster and of the covalently bound coenzyme of trimethylamine dehydrogenase in catalysis. Bacterial trimethylamine dehydrogenase contains a novel type of covalently bound flavin mononucleotide and a tetrameric iron-sulphur centre. The dehydrogenase takes up 1.5mol of dithionite/mol of enzyme and is thereby converted into the flavin quinol-reduced (4Fe-4S) form, with the expected bleaching of the visible absorption band of the flavin and the emergence of signals of typical reduced ferredoxin in the electronparamagnetic-resonance spectrum. On reduction with a slight excess of substrate, however, unusual absorption and electron-paramagnetic-resonance spectra appear quite rapidly. The latter is attributed to extensive interaction between the reduced (4Fe-4S) centre and the flavin semiquinone. The species of enzyme arising during the catalytic cycle were studied by a combination of rapid-freeze e.p.r. and stopped-flow spectophotometry. The initial reduction of the flavin to the quinol form is far too rapid to be rate-limiting in catalysis, as is the reoxidation of the substrate-reduced enzyme by phenazine methosulphate. Formation of the spin-spin-interacting species from the dihydroflavin is considerably slower, however, and it may be the rate-limiting step in the catalytic cycle, since its rate of formation agrees reasonably well with the catalytic-centre activity determined in steady-state kinetic assays. In addition to the interacting form, a second form of the enzyme was noted during reduction by trimethylamine, differing in absorption spectrum, the structure of which remains to be determined."}
{"id": "PMID:204298", "title": "Phosphorylation of additional sites on pyruvate dehydrogenase inhibits its re-activation by pyruvate dehydrogenase phosphate phosphatase.", "content": "The phosphorylation of sites additional to an inactivating site inhibits the formation of active pig heart pyruvate dehydrogenase complex from inactive pyruvate dehydrogenase phosphate complex by pig heart pyruvate dehydrogenase phosphate phosphatase.", "contents": "Phosphorylation of additional sites on pyruvate dehydrogenase inhibits its re-activation by pyruvate dehydrogenase phosphate phosphatase. The phosphorylation of sites additional to an inactivating site inhibits the formation of active pig heart pyruvate dehydrogenase complex from inactive pyruvate dehydrogenase phosphate complex by pig heart pyruvate dehydrogenase phosphate phosphatase."}
{"id": "PMID:204299", "title": "Effect of hepatic injury on prolyl 3-hydroxylase and 4-hydroxylase activities in rat liver and on immunoreactive prolyl 4-hydroxylase concentrations in the liver and serum.", "content": "After severe hepatic injury induced by dimethylnitrosamine, approximately a 4-fold increase in hepatic prolyl 4-hydroxylase activity occurred within 4 days, whereas the increases in total immunoreactive prolyl 4-hydroxylase protein and in prolyl 3-hydroxylase activity were only about 1.4-fold. The different magnitudes of the increases in the prolyl 4-hydroxylase and 3-hydroxylase activities were verified after partial purification of the enzymes by gel filtration. The data support previous reports indicating differential increases in the activities of individual enzymes of collagen biosynthesis in hepatic injury. Separation of prolyl 4-hydroxylase tetramers from the monomer-size protein by gel filtration indicated that the increase in enzyme activity was similar to that in enzyme tetramers, and an increase had also occurred in the ratio of enzyme tetramers to total enzyme protein. Thus the specific activity of the tetramers had remained unchanged in liver injury. The administration of dimethylnitrosamine was also accompanied by a marked increase in the immunoreactive prolyl 4-hydroxylase protein concentration in the serum, and a similar effect was also noted after carbon tetrachloride administration, results suggesting that the increases originated in the liver.", "contents": "Effect of hepatic injury on prolyl 3-hydroxylase and 4-hydroxylase activities in rat liver and on immunoreactive prolyl 4-hydroxylase concentrations in the liver and serum. After severe hepatic injury induced by dimethylnitrosamine, approximately a 4-fold increase in hepatic prolyl 4-hydroxylase activity occurred within 4 days, whereas the increases in total immunoreactive prolyl 4-hydroxylase protein and in prolyl 3-hydroxylase activity were only about 1.4-fold. The different magnitudes of the increases in the prolyl 4-hydroxylase and 3-hydroxylase activities were verified after partial purification of the enzymes by gel filtration. The data support previous reports indicating differential increases in the activities of individual enzymes of collagen biosynthesis in hepatic injury. Separation of prolyl 4-hydroxylase tetramers from the monomer-size protein by gel filtration indicated that the increase in enzyme activity was similar to that in enzyme tetramers, and an increase had also occurred in the ratio of enzyme tetramers to total enzyme protein. Thus the specific activity of the tetramers had remained unchanged in liver injury. The administration of dimethylnitrosamine was also accompanied by a marked increase in the immunoreactive prolyl 4-hydroxylase protein concentration in the serum, and a similar effect was also noted after carbon tetrachloride administration, results suggesting that the increases originated in the liver."}
{"id": "PMID:204300", "title": "Glycerolipid biosynthesis in rat adipose tissue. Influence of adipose-cell size and site of adipose tissue on triacylglycerol formation in lean and obese rats.", "content": "The rates of lipid formation were compared in different fat-depots from lean and obese rats by using [14C]glycerol 3-phosphate, [14C]glucose or [14C]acetate as substrates. In lean animals, subcutaneous adipose tissue showed significantly lower rates of lipid synthesis than did perirenal and gonadal fat-tissue. In obese animals, the rates of lipid synthesis were significantly higher and did not vary from one fat-depot to another. Differences in the rates of lipid formation between lean and obese rats disappeared during dietary restriction of obese animals. The isolated adipocyte preparation did not reflect the true metabolic activity of the adipose organ, since this preparation was mainly derived from smaller adipocytes that were metabolically less active than larger adipocytes. The present study suggests that it is better to use whole tissue preparations to measure lipogenesis and esterification reactions, because these measurements represent the contribution of both larger and smaller adipocytes towards lipid formation.", "contents": "Glycerolipid biosynthesis in rat adipose tissue. Influence of adipose-cell size and site of adipose tissue on triacylglycerol formation in lean and obese rats. The rates of lipid formation were compared in different fat-depots from lean and obese rats by using [14C]glycerol 3-phosphate, [14C]glucose or [14C]acetate as substrates. In lean animals, subcutaneous adipose tissue showed significantly lower rates of lipid synthesis than did perirenal and gonadal fat-tissue. In obese animals, the rates of lipid synthesis were significantly higher and did not vary from one fat-depot to another. Differences in the rates of lipid formation between lean and obese rats disappeared during dietary restriction of obese animals. The isolated adipocyte preparation did not reflect the true metabolic activity of the adipose organ, since this preparation was mainly derived from smaller adipocytes that were metabolically less active than larger adipocytes. The present study suggests that it is better to use whole tissue preparations to measure lipogenesis and esterification reactions, because these measurements represent the contribution of both larger and smaller adipocytes towards lipid formation."}
{"id": "PMID:204301", "title": "Cellular site and state combination of the adenosine 3':5'-cyclic monophosphate persisting after excitation of cerebral tissues.", "content": "1. The subcellular distribution of cyclic AMP in guinea-pig cerebral-cortical tissue was determined before and after electrical stimulation, and after a period of continued incubation after electrical stimulation, with and without the presence of histamine. 2. Electrical stimulation and histamine increased the cyclic AMP content of all fractions, the greatest increase occurring in the supernatant fraction. 3. Continued incubation after cessation of electrical stimulation diminished the cyclic AMP of the total homogenate and supernatant fractions, but increased that of the synaptosomal fraction. 4. Further fractionation of the synaptosomal fractions from stimulated tissues suggested that most of their soluble cyclic AMP was in a higher-molecular-weight form than was that of the tissue supernatant. 5. It is suggested that protein binding and cytoplasmic transport of cyclic AMP are involved in the changes observed.", "contents": "Cellular site and state combination of the adenosine 3':5'-cyclic monophosphate persisting after excitation of cerebral tissues. 1. The subcellular distribution of cyclic AMP in guinea-pig cerebral-cortical tissue was determined before and after electrical stimulation, and after a period of continued incubation after electrical stimulation, with and without the presence of histamine. 2. Electrical stimulation and histamine increased the cyclic AMP content of all fractions, the greatest increase occurring in the supernatant fraction. 3. Continued incubation after cessation of electrical stimulation diminished the cyclic AMP of the total homogenate and supernatant fractions, but increased that of the synaptosomal fraction. 4. Further fractionation of the synaptosomal fractions from stimulated tissues suggested that most of their soluble cyclic AMP was in a higher-molecular-weight form than was that of the tissue supernatant. 5. It is suggested that protein binding and cytoplasmic transport of cyclic AMP are involved in the changes observed."}
{"id": "PMID:204302", "title": "Regulation of the synthesis of lutropin-induced protein in rat testis Leydig cells.", "content": "The mechanism of action of lutropin on the stimulation of the synthesis of a specific lutropin-induced protein in rat testis Leydig cells was investigated. Lutropin-induced protein has a mol.wt. of approx. 21000 and is detected by labelling the Leydig-cell proteins with [(35)S]methionine, followed by separation by polyacrylamide-gel electrophoresis and radioautography of the dried gel. The incorporation of (35)S into lutropin-induced protein was used as an estimate for the synthesis of the protein. Incubation of Leydig cells with dibutyryl cyclic AMP or cholera toxin also resulted in the stimulation of synthesis of the protein. Synthesis of lutropin-induced protein, when maximally stimulated with 100ng of lutropin/ml, could not be stimulated further by addition of dibutyryl cyclic AMP. Addition of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, further increased synthesis of the protein in the presence of a submaximal dose of lutropin (10ng/ml) but not in the absence of lutropin or with maximal amounts of lutropin (100 and 1000ng/ml). Actinomycin D prevented the effect of lutropin on the stimulation of lutropin-induced protein synthesis when added immediately or 1h after the start of the incubation, but not when added after 5-6h. This is interpreted as reflecting that, after induction of mRNA coding for lutropin-induced protein, lutropin had no influence on the synthesis of the protein in the presence of actinomycin D. Synthesis of the protein was also stimulated in vivo by injection of choriogonadotropin into rats 1 day after hypophysectomy, and the time course of this stimulation of lutropin-induced protein synthesis in vivo was similar to that obtained by incubating Leydig cells in vitro with lutropin. From these results it is concluded that stimulation of lutropin-induced protein synthesis by lutropin is most probably mediated by cyclic AMP and involves synthesis of mRNA.", "contents": "Regulation of the synthesis of lutropin-induced protein in rat testis Leydig cells. The mechanism of action of lutropin on the stimulation of the synthesis of a specific lutropin-induced protein in rat testis Leydig cells was investigated. Lutropin-induced protein has a mol.wt. of approx. 21000 and is detected by labelling the Leydig-cell proteins with [(35)S]methionine, followed by separation by polyacrylamide-gel electrophoresis and radioautography of the dried gel. The incorporation of (35)S into lutropin-induced protein was used as an estimate for the synthesis of the protein. Incubation of Leydig cells with dibutyryl cyclic AMP or cholera toxin also resulted in the stimulation of synthesis of the protein. Synthesis of lutropin-induced protein, when maximally stimulated with 100ng of lutropin/ml, could not be stimulated further by addition of dibutyryl cyclic AMP. Addition of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, further increased synthesis of the protein in the presence of a submaximal dose of lutropin (10ng/ml) but not in the absence of lutropin or with maximal amounts of lutropin (100 and 1000ng/ml). Actinomycin D prevented the effect of lutropin on the stimulation of lutropin-induced protein synthesis when added immediately or 1h after the start of the incubation, but not when added after 5-6h. This is interpreted as reflecting that, after induction of mRNA coding for lutropin-induced protein, lutropin had no influence on the synthesis of the protein in the presence of actinomycin D. Synthesis of the protein was also stimulated in vivo by injection of choriogonadotropin into rats 1 day after hypophysectomy, and the time course of this stimulation of lutropin-induced protein synthesis in vivo was similar to that obtained by incubating Leydig cells in vitro with lutropin. From these results it is concluded that stimulation of lutropin-induced protein synthesis by lutropin is most probably mediated by cyclic AMP and involves synthesis of mRNA."}
{"id": "PMID:204303", "title": "The relationship between vitamin D-stimulated calcium transport and intestinal calcium-binding protein in the chicken.", "content": "1. The rapid stimulation of intestinal Ca(2+) transport observed in vitamin D-deficient chicks after receiving 1,25-dihydroxycholecalciferol has necessitated a re-evaluation of the correlation hitherto observed between this stimulation and the induction of calcium-binding protein synthesis. By 1h after a dose of 125ng of 1,25-dihydroxycholecalciferol, Ca(2+) transport is increased. This is at least 2h before calcium-binding protein can be detected immunologically and 1h before synthesis of the protein begins on polyribosomes, and thus the hormone stimulates Ca(2+) transport before calcium-binding-protein biosynthesis is induced. 2. The maximum increase in Ca(2+) transport observed after this dose of 1,25-dihydroxycholecalciferol (attained by 8h) is similar to that observed after 1.25-25mug of cholecalciferol, but the stimulation is only short-lived, in contrast with the effect observed after the vitamin. At later times after the hormone, however, when Ca(2+) transport has declined to its basal rate, the cellular content of calcium-binding protein remains elevated. 3. Calcium-binding protein is synthesized on free rather than membrane-bound polyribosomes, which implies that it is an intracellular protein. 4. Rachitic chicks require the presence of dietary calcium for maximum stimulation of calcium-binding protein production by cholecalciferol. 5. These results suggest that calcium-binding protein is an intracellular protein, and that its synthesis may be a consequence of the raised intracellular calcium content of the intestinal epithelial cells resulting from 1,25-dihydroxycholecalciferol-stimulated Ca(2+) transport. We propose that calcium-binding-protein synthesis is necessary for maintaining the stimulated rate of Ca(2+) transport, which is initiated by other factors.", "contents": "The relationship between vitamin D-stimulated calcium transport and intestinal calcium-binding protein in the chicken. 1. The rapid stimulation of intestinal Ca(2+) transport observed in vitamin D-deficient chicks after receiving 1,25-dihydroxycholecalciferol has necessitated a re-evaluation of the correlation hitherto observed between this stimulation and the induction of calcium-binding protein synthesis. By 1h after a dose of 125ng of 1,25-dihydroxycholecalciferol, Ca(2+) transport is increased. This is at least 2h before calcium-binding protein can be detected immunologically and 1h before synthesis of the protein begins on polyribosomes, and thus the hormone stimulates Ca(2+) transport before calcium-binding-protein biosynthesis is induced. 2. The maximum increase in Ca(2+) transport observed after this dose of 1,25-dihydroxycholecalciferol (attained by 8h) is similar to that observed after 1.25-25mug of cholecalciferol, but the stimulation is only short-lived, in contrast with the effect observed after the vitamin. At later times after the hormone, however, when Ca(2+) transport has declined to its basal rate, the cellular content of calcium-binding protein remains elevated. 3. Calcium-binding protein is synthesized on free rather than membrane-bound polyribosomes, which implies that it is an intracellular protein. 4. Rachitic chicks require the presence of dietary calcium for maximum stimulation of calcium-binding protein production by cholecalciferol. 5. These results suggest that calcium-binding protein is an intracellular protein, and that its synthesis may be a consequence of the raised intracellular calcium content of the intestinal epithelial cells resulting from 1,25-dihydroxycholecalciferol-stimulated Ca(2+) transport. We propose that calcium-binding-protein synthesis is necessary for maintaining the stimulated rate of Ca(2+) transport, which is initiated by other factors."}
{"id": "PMID:204315", "title": "[Antiviral effect of aqueous plant extracts in tissue culture].", "content": "The aqueous extracts from 178 kinds of medicinal plants belonging to 69 families were examined from the point of their virustatic activity against herpes-, influenza-, vaccine- and poliovirus. 75 kinds proved to be virustatic against one or more kinds of virus. Nearly one-third of the active plants belong to families that are known as especially rich in tannin. Besides the virustatic activity a great number of extracts showed also a cytostatic activity.", "contents": "[Antiviral effect of aqueous plant extracts in tissue culture]. The aqueous extracts from 178 kinds of medicinal plants belonging to 69 families were examined from the point of their virustatic activity against herpes-, influenza-, vaccine- and poliovirus. 75 kinds proved to be virustatic against one or more kinds of virus. Nearly one-third of the active plants belong to families that are known as especially rich in tannin. Besides the virustatic activity a great number of extracts showed also a cytostatic activity."}
{"id": "PMID:204316", "title": "Low-fat diet versus low-carbohydrate diet in the treatment of type IV hyperlipoproteinaemia.", "content": "The response to dietary management was studied in 24 hypertriglyceridaemic out-patients. Fourteen patients were kept on a diet low in fat and cholesterol and high in polyunsaturated fatty acids; 10 of these patients subsequently followed a period of low-carbohydrate diet. At the end of the first period a significant decrease of serum triglyceride, cholesterol and beta-lipoproteins was observed; after the second feeding period no substantial change of serum lipoprotein pattern occurred. Ten patients were given a low-carbohydrate diet that produced a significant fall of the levels of triglycerides and pre-beta-lipoproteins. Six of these subjects continued the experiment with the low-fat diet; during this period a further trend toward reduction of serum triglyceride, cholesterol and beta-lipoproteins was observed which, however, was not statistically significant. We conclude that serum triglyceride levels can be lowered both by a low-carbohydrate diet and by a low-fat diet, but the latter has the advantage of also producing a significant fall of serum cholesterol and beta-lipoproteins.", "contents": "Low-fat diet versus low-carbohydrate diet in the treatment of type IV hyperlipoproteinaemia. The response to dietary management was studied in 24 hypertriglyceridaemic out-patients. Fourteen patients were kept on a diet low in fat and cholesterol and high in polyunsaturated fatty acids; 10 of these patients subsequently followed a period of low-carbohydrate diet. At the end of the first period a significant decrease of serum triglyceride, cholesterol and beta-lipoproteins was observed; after the second feeding period no substantial change of serum lipoprotein pattern occurred. Ten patients were given a low-carbohydrate diet that produced a significant fall of the levels of triglycerides and pre-beta-lipoproteins. Six of these subjects continued the experiment with the low-fat diet; during this period a further trend toward reduction of serum triglyceride, cholesterol and beta-lipoproteins was observed which, however, was not statistically significant. We conclude that serum triglyceride levels can be lowered both by a low-carbohydrate diet and by a low-fat diet, but the latter has the advantage of also producing a significant fall of serum cholesterol and beta-lipoproteins."}
{"id": "PMID:204317", "title": "Acute effects of cholestyramine on serum lipoprotein concentrations in type II hyperlipoproteinaemia.", "content": "Twelve subjects with primary type IIA hyperlipoproteinaemia were treated with cholestyramine under metabolic ward conditions in order to study the timing of effects of different serum lipoprotein classes. After 1 day's treatment changes occurred in all 3 classes, i.e., very low (VLDL), low (LDL) and high (HDL) density lipoprotein classes. VLDL increased abruptly and remained constant during treatment. The ratio of cholesterol/triglycerides decreased suggesting the formation of larger particles. LDL cholesterol decreased continuously suggesting a different mechanism behind this effect than that on VLDL. LDL triglyceride remained constant indicating a relative increase of LDL1. HDL cholesterol decreased while HDL triglycerides increased. All changes made the lipoprotein pattern more \"type IV-like\". The findings were in agreement with an increased formation of VLDL and an increased flux of lipoprotein through the cascade VLDL-IDL-LDL1-LDL2.", "contents": "Acute effects of cholestyramine on serum lipoprotein concentrations in type II hyperlipoproteinaemia. Twelve subjects with primary type IIA hyperlipoproteinaemia were treated with cholestyramine under metabolic ward conditions in order to study the timing of effects of different serum lipoprotein classes. After 1 day's treatment changes occurred in all 3 classes, i.e., very low (VLDL), low (LDL) and high (HDL) density lipoprotein classes. VLDL increased abruptly and remained constant during treatment. The ratio of cholesterol/triglycerides decreased suggesting the formation of larger particles. LDL cholesterol decreased continuously suggesting a different mechanism behind this effect than that on VLDL. LDL triglyceride remained constant indicating a relative increase of LDL1. HDL cholesterol decreased while HDL triglycerides increased. All changes made the lipoprotein pattern more \"type IV-like\". The findings were in agreement with an increased formation of VLDL and an increased flux of lipoprotein through the cascade VLDL-IDL-LDL1-LDL2."}
{"id": "PMID:204320", "title": "RNA-tumour-virus genes and transforming genes: patterns of transmission.", "content": "RNA tumour virus genes are contained in the chromosomal DNA of most vertebrates, and may be transmitted vertically from parent to progeny along with other cellular genes, as well as horizontally as infectious particles. Activation of these viral genes may be part of the means by which RNA tumour viruses produce cancer. Viral genes and their possible gene products have been characterized. The envelope glycoprotein, for example, interacts with specific membrane receptors on cell surfaces and the major phosphoprotein binds to specific viral RNA sequences. Type-C viral gene sequences have evolved as the species have evolved, and have been transferred between distantly related species under natural conditions. The presence of genetically transmitted viral genes in several vertebrate species, including primates, and the evidence that they may provide normal functions beneficial to the species carrying them, suggests that the potential to cause cancer is a pathological manifestation of a normal physiological process.", "contents": "RNA-tumour-virus genes and transforming genes: patterns of transmission. RNA tumour virus genes are contained in the chromosomal DNA of most vertebrates, and may be transmitted vertically from parent to progeny along with other cellular genes, as well as horizontally as infectious particles. Activation of these viral genes may be part of the means by which RNA tumour viruses produce cancer. Viral genes and their possible gene products have been characterized. The envelope glycoprotein, for example, interacts with specific membrane receptors on cell surfaces and the major phosphoprotein binds to specific viral RNA sequences. Type-C viral gene sequences have evolved as the species have evolved, and have been transferred between distantly related species under natural conditions. The presence of genetically transmitted viral genes in several vertebrate species, including primates, and the evidence that they may provide normal functions beneficial to the species carrying them, suggests that the potential to cause cancer is a pathological manifestation of a normal physiological process."}
{"id": "PMID:204321", "title": "Extraction of CEA from tumour tissue, foetal colon and patients' sera, and the effect of perchloric acid.", "content": "The use of perchloric acid and water for the extraction of CEA from tumour and foetal tissues has been investigated. In the case of tumour, lower recoveries of CEA were obtained from perchloric acid extracts than from aqueous extracts of the same tissue. CEA has also been extracted with 3M KCl solution from insoluble perchloric acid residues of tumour homogenates and cancer patients' serum. Whilst a large proportion of CEA activity recovered from tumour was associated with the perchloric acid residue, the corresponding amounts from serum were very small. CEA elution volumes for each extract, obtained by assay of Sephadex G-200 column fractions, showed significant heterogeneity in molecular size. The purified CEA pools also showed quantitative variations in the binding profiles on Con A-Sepharose. It has been shown that perchloric acid modifies the carbohydrate in CEA, thus altering its Con A-binding properties. Preliminary experiments with foetal colon have demonstrated that, unlike colorectal CEA, a significant proportion of foetal CEA was not bound to ConA. Comparative immunodiffusion showed immunological identity of CEA from the various extracts, although the purified aqueous extract produced an additional precipitin reaction, indicating a second antigen which is relatively unstable or less soluble in perchloric acid.", "contents": "Extraction of CEA from tumour tissue, foetal colon and patients' sera, and the effect of perchloric acid. The use of perchloric acid and water for the extraction of CEA from tumour and foetal tissues has been investigated. In the case of tumour, lower recoveries of CEA were obtained from perchloric acid extracts than from aqueous extracts of the same tissue. CEA has also been extracted with 3M KCl solution from insoluble perchloric acid residues of tumour homogenates and cancer patients' serum. Whilst a large proportion of CEA activity recovered from tumour was associated with the perchloric acid residue, the corresponding amounts from serum were very small. CEA elution volumes for each extract, obtained by assay of Sephadex G-200 column fractions, showed significant heterogeneity in molecular size. The purified CEA pools also showed quantitative variations in the binding profiles on Con A-Sepharose. It has been shown that perchloric acid modifies the carbohydrate in CEA, thus altering its Con A-binding properties. Preliminary experiments with foetal colon have demonstrated that, unlike colorectal CEA, a significant proportion of foetal CEA was not bound to ConA. Comparative immunodiffusion showed immunological identity of CEA from the various extracts, although the purified aqueous extract produced an additional precipitin reaction, indicating a second antigen which is relatively unstable or less soluble in perchloric acid."}
{"id": "PMID:204322", "title": "Malignant neoplasms in rats fed lasiocarpine.", "content": "Lasiocarpine, a pyrrolizidine alkaloid, was fed at a dietary concentration of 50/10(6) for 55 weeks, to 20 male F-344 rats. Malignant tumours developed in 17/20 animals between 48 and 59 weeks. Forty-five percent (9/20) developed angiosarcomas of the liver and 35% (7/20) had hepatocellular carcinomas. Other tumours included malignant adnexas tumour of the skin (1 rat) and lympohoma (1 rat). Lung metastases were observed in 4 animals with angiosarcoma of the liver and one animal with hepatocellular carcinoma. From one animal, angiosarcoma was successfully transplanted through 4 generations.", "contents": "Malignant neoplasms in rats fed lasiocarpine. Lasiocarpine, a pyrrolizidine alkaloid, was fed at a dietary concentration of 50/10(6) for 55 weeks, to 20 male F-344 rats. Malignant tumours developed in 17/20 animals between 48 and 59 weeks. Forty-five percent (9/20) developed angiosarcomas of the liver and 35% (7/20) had hepatocellular carcinomas. Other tumours included malignant adnexas tumour of the skin (1 rat) and lympohoma (1 rat). Lung metastases were observed in 4 animals with angiosarcoma of the liver and one animal with hepatocellular carcinoma. From one animal, angiosarcoma was successfully transplanted through 4 generations."}
{"id": "PMID:204323", "title": "Changes in whole blood and serum components during Francisella tularensis and rabbit pox infections of rabbits.", "content": "Rabbits infected with virulent Francisella tularensis strain Schu S4 or rabbit pox virus (Utrecht strain) showed significant early changes in serum levels of trace metals, neutral fat and alkaline phosphatase activity. With F. tularensis infections a marked early leukopenia and a decrease in serum amino acids were also observed; the effect on amino acid levels was less pronounced in rabbit pox infections. In both diseases these changes preceded the appearance of acute phase globulins in the serum. Vaccination with the live vaccine strain of F. tularensis slightly increased survival times but did not delay the onset of metabolic changes in rabbits subsequently infected with the virulent Schu S4 strain.", "contents": "Changes in whole blood and serum components during Francisella tularensis and rabbit pox infections of rabbits. Rabbits infected with virulent Francisella tularensis strain Schu S4 or rabbit pox virus (Utrecht strain) showed significant early changes in serum levels of trace metals, neutral fat and alkaline phosphatase activity. With F. tularensis infections a marked early leukopenia and a decrease in serum amino acids were also observed; the effect on amino acid levels was less pronounced in rabbit pox infections. In both diseases these changes preceded the appearance of acute phase globulins in the serum. Vaccination with the live vaccine strain of F. tularensis slightly increased survival times but did not delay the onset of metabolic changes in rabbits subsequently infected with the virulent Schu S4 strain."}
{"id": "PMID:204324", "title": "Fabry's disease: biochemical and histochemical studies on hair roots for carrier detection.", "content": "A method of assay alpha-galactosidase and acid phosphatase activities in single hair roots is described. Enzyme histochemical studies show that the distribution of acid phosphatase in the human hair root matches that of alpha-galactosidase. Histochemically, the main activity is located in the upper part of the sheath near the orifice of the duct of the sebaceous gland. This is confirmed by enzyme assays on different parts of the hair root after dissection. The variation in the values found in individual hair roots is improved by relating alpha-galactosidase to acid phosphatase activities. Storage experiments indicate a remarkable stability of both alpha-galactosidase and acid phosphatase in human hair roots.", "contents": "Fabry's disease: biochemical and histochemical studies on hair roots for carrier detection. A method of assay alpha-galactosidase and acid phosphatase activities in single hair roots is described. Enzyme histochemical studies show that the distribution of acid phosphatase in the human hair root matches that of alpha-galactosidase. Histochemically, the main activity is located in the upper part of the sheath near the orifice of the duct of the sebaceous gland. This is confirmed by enzyme assays on different parts of the hair root after dissection. The variation in the values found in individual hair roots is improved by relating alpha-galactosidase to acid phosphatase activities. Storage experiments indicate a remarkable stability of both alpha-galactosidase and acid phosphatase in human hair roots."}
{"id": "PMID:204325", "title": "Multicentric reticulohistiocytosis and malignant disease.", "content": "Multicentric reticulohistiocytosis developed in a 45-year-old woman, who had a 3 year history of untreated breast carcinoma. A review of the literature revealed that malignant disease has been associated with 27% of reported cases. It is considered that, like adult dermatomyositis, the onset of multicentric reticulohistiocytosis should stimulate detailed investigation for an underlying neoplasm.", "contents": "Multicentric reticulohistiocytosis and malignant disease. Multicentric reticulohistiocytosis developed in a 45-year-old woman, who had a 3 year history of untreated breast carcinoma. A review of the literature revealed that malignant disease has been associated with 27% of reported cases. It is considered that, like adult dermatomyositis, the onset of multicentric reticulohistiocytosis should stimulate detailed investigation for an underlying neoplasm."}
{"id": "PMID:204326", "title": "Interaction between silica and hydrophobic cations.", "content": "The interactions between silica and some molecules which have a high affinity for its surface have been studied. The hydrophobic properties and the positive charge of these molecules are likely to be responsible for their strong adsorption on to silica. These observations should be useful in research into new inhibitors of the effects of silica. One of the cations tested, chloroquine, has been shown to be an effective inhibitor of the haemolytic activity of quartz.", "contents": "Interaction between silica and hydrophobic cations. The interactions between silica and some molecules which have a high affinity for its surface have been studied. The hydrophobic properties and the positive charge of these molecules are likely to be responsible for their strong adsorption on to silica. These observations should be useful in research into new inhibitors of the effects of silica. One of the cations tested, chloroquine, has been shown to be an effective inhibitor of the haemolytic activity of quartz."}
{"id": "PMID:204327", "title": "The similarity between alkaline phosphatase (EC 3.1.3.1) and phytase (EC 3.1.3.8) activities in rat intestine and their importance in phytate-induced zinc deficiency.", "content": "1. The activities of alkaline phosphatase (EC 3.1.3.1) and phytase (EC 3.1.3.8) were similarly distributed in the small intestine of rats. Regional differences in activity were reflected by similar differences in the capacity of ligated intestinal segments to hydrolyse phytate in vivo. Activities were greatest in the duodenum and lowest in the terminal ileum. 2. Specific activities of both enzymes were tenfold greater in the brush border fraction of duodenal mucosa compared with entire mucosal homogenates. 3. Brush-border alkaline phosphatase and phytase activities required both magnesium and zinc ions for maximal activity. 4. Zn deficiency induced by feeding a diet low in Zn (0.5 mg Zn/kg) caused similar reductions in activity of both enzymes. 5. Zn deficiency induced by feeding diets marginally adequate in Zn (12 mg/kg) and phytate (10 g/kg) caused reductions in alkaline phosphatase, phytase activities and phytate hydrolysis in vivo. 6. It is suggested that phytase activity is a manifestation of alkaline phosphatase and the significance of this in relation to phytate-induced in Zn deficiency is discussed.", "contents": "The similarity between alkaline phosphatase (EC 3.1.3.1) and phytase (EC 3.1.3.8) activities in rat intestine and their importance in phytate-induced zinc deficiency. 1. The activities of alkaline phosphatase (EC 3.1.3.1) and phytase (EC 3.1.3.8) were similarly distributed in the small intestine of rats. Regional differences in activity were reflected by similar differences in the capacity of ligated intestinal segments to hydrolyse phytate in vivo. Activities were greatest in the duodenum and lowest in the terminal ileum. 2. Specific activities of both enzymes were tenfold greater in the brush border fraction of duodenal mucosa compared with entire mucosal homogenates. 3. Brush-border alkaline phosphatase and phytase activities required both magnesium and zinc ions for maximal activity. 4. Zn deficiency induced by feeding a diet low in Zn (0.5 mg Zn/kg) caused similar reductions in activity of both enzymes. 5. Zn deficiency induced by feeding diets marginally adequate in Zn (12 mg/kg) and phytate (10 g/kg) caused reductions in alkaline phosphatase, phytase activities and phytate hydrolysis in vivo. 6. It is suggested that phytase activity is a manifestation of alkaline phosphatase and the significance of this in relation to phytate-induced in Zn deficiency is discussed."}
{"id": "PMID:204330", "title": "Collagen biosynthesis by cultured Chinese hamster lung cells. Cell-free synthesis of procollagen alpha chains.", "content": "Cell-free extracts from the HTl clone of cultured Chinese hamster lung cells efficiently promote the incorporation of proline into newly synthesized material, 50% of which is digestible to small peptides by highly purified bacterial collagenase. The synthesis of the these products occurs under optimal protein synthesis conditions and is inhibited by puromycin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cell-free synthesized material reveals a major collagenase sensitive peak (20% of the total product) at mol wt 165 000 which is reflected by a collagenase sensitive material of similar size in the culture medium. Two additional collagenase digestible species (mol wt 95000 and 65000), each having a corresponding secreted product, are generated by the cell-free system. These results are consistent with the concept that procollagen is formed by the association of three individually translated pro alphachains. The data further constitute the report of a highly active homologous cell-free system capable of pro alpha chain biosynthesis derived from a cultured cell line that is a practical source for pro alphachain biosynthesis derived from a cultured cell line that is a practical source for proalpha chain mRNA as well as a unique system for elucidating regulatory mechanisms involved in collagen biosynthesis.", "contents": "Collagen biosynthesis by cultured Chinese hamster lung cells. Cell-free synthesis of procollagen alpha chains. Cell-free extracts from the HTl clone of cultured Chinese hamster lung cells efficiently promote the incorporation of proline into newly synthesized material, 50% of which is digestible to small peptides by highly purified bacterial collagenase. The synthesis of the these products occurs under optimal protein synthesis conditions and is inhibited by puromycin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cell-free synthesized material reveals a major collagenase sensitive peak (20% of the total product) at mol wt 165 000 which is reflected by a collagenase sensitive material of similar size in the culture medium. Two additional collagenase digestible species (mol wt 95000 and 65000), each having a corresponding secreted product, are generated by the cell-free system. These results are consistent with the concept that procollagen is formed by the association of three individually translated pro alphachains. The data further constitute the report of a highly active homologous cell-free system capable of pro alpha chain biosynthesis derived from a cultured cell line that is a practical source for pro alphachain biosynthesis derived from a cultured cell line that is a practical source for proalpha chain mRNA as well as a unique system for elucidating regulatory mechanisms involved in collagen biosynthesis."}
{"id": "PMID:204332", "title": "Circular dichroism studies of the interaction of a limited hydrolysate of T4 gene 32 protein with T4 DNA and poly[d(A-T)].poly[d(A-T)].", "content": "gp32 I is a protein with a molecular weight of 27 000. It is obtained by limited hydrolysis of T4 gene 32 coded protein, which is one of the DNA melting proteins. gp32 I itself appears to be also a melting protein. It denatures poly[d(A-T)].poly[d(A-T)] and T4 DNA at temperatures far (50-60 degrees C) below their regular melting temperatures. Under similar conditions gp32 I will denature poly[d(A-T).poly[d(A-T)] at temperatures approximately 12 degrees C lower than those measured for the intact gp32 denaturation. For T4 DNA gp32 shows no melting behavior while gp32 I shows considerable denaturation (i.e., hyperchromicity) even at 1 degree C. In this paper the denaturation of poly[d(A-T)].poly[d(A-T)] and T4 DNA by gp32 I is studied by means of circular dichroism. It appears that gp32 I forms a complex with poly[d(A-T)]. The conformation of the polynucleotide in the complex is equal to that of one strand of the double-stranded polymer in 6 M LiCl. In the gp32 I DNA complex formed upon denaturation of T4 DNA, the single-stranded DNA molecule has the same conformation as one strand of the double-strand T4 DNA molecule in the C-DNA conformation.", "contents": "Circular dichroism studies of the interaction of a limited hydrolysate of T4 gene 32 protein with T4 DNA and poly[d(A-T)].poly[d(A-T)]. gp32 I is a protein with a molecular weight of 27 000. It is obtained by limited hydrolysis of T4 gene 32 coded protein, which is one of the DNA melting proteins. gp32 I itself appears to be also a melting protein. It denatures poly[d(A-T)].poly[d(A-T)] and T4 DNA at temperatures far (50-60 degrees C) below their regular melting temperatures. Under similar conditions gp32 I will denature poly[d(A-T).poly[d(A-T)] at temperatures approximately 12 degrees C lower than those measured for the intact gp32 denaturation. For T4 DNA gp32 shows no melting behavior while gp32 I shows considerable denaturation (i.e., hyperchromicity) even at 1 degree C. In this paper the denaturation of poly[d(A-T)].poly[d(A-T)] and T4 DNA by gp32 I is studied by means of circular dichroism. It appears that gp32 I forms a complex with poly[d(A-T)]. The conformation of the polynucleotide in the complex is equal to that of one strand of the double-stranded polymer in 6 M LiCl. In the gp32 I DNA complex formed upon denaturation of T4 DNA, the single-stranded DNA molecule has the same conformation as one strand of the double-strand T4 DNA molecule in the C-DNA conformation."}
{"id": "PMID:204333", "title": "Alkaline phosphatase: affinity chromatography and inhibition by phosphonic acids.", "content": "Five phosphonic acid derivatives were synthesized, coupled to agarose, and tested for affinity chromatographic binding of alkaline phosphatase from bovine intestine. Agarose coupled to L-histidyldiazobenzylphosphonic acid was found to be a highly effective adsorbent. In order to understand the large differences in binding capacity observed with derivatized agaroses, inhibition of alkaline phosphatase by phosphonic acid ligands, and related phosphonic acids, was measured. The results of affinity chromatography and inhibition studies were in good agreement, demonstrating that phosphonic acids with large aromatic/hydrophobic, carboxylate substituents bind strongly and competitively to the enzyme active site.", "contents": "Alkaline phosphatase: affinity chromatography and inhibition by phosphonic acids. Five phosphonic acid derivatives were synthesized, coupled to agarose, and tested for affinity chromatographic binding of alkaline phosphatase from bovine intestine. Agarose coupled to L-histidyldiazobenzylphosphonic acid was found to be a highly effective adsorbent. In order to understand the large differences in binding capacity observed with derivatized agaroses, inhibition of alkaline phosphatase by phosphonic acid ligands, and related phosphonic acids, was measured. The results of affinity chromatography and inhibition studies were in good agreement, demonstrating that phosphonic acids with large aromatic/hydrophobic, carboxylate substituents bind strongly and competitively to the enzyme active site."}
{"id": "PMID:204337", "title": "Comparative kinetic studies of cytochromes c in reactions with mitochondrial cytochrome c oxidase and reductase.", "content": "Kinetic studies of the reactions of selected eukaryotic and prokaryotic cytochromes c with mitochondrial cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase (EC 1.9.3.1) using a standardized complex IV preparation from beef heart are reported. Data on reactions with NADH-linked cytochrome c reductase (complexes I and III) are included. The concentration ranges employed provide a basis for quantitative demonstration of a general rate law applicable to oxidase reactions of cytochrome c of greatly differing reactivities. Results are interpreted on the basis of a modified Minnaert mechanism (Minnaert, K. (1961) Biochim. Biophys. Acta 50, 23), assuming productive complex formation between cytochrome c and free oxidase in addition to further complex binding of a second cytochrome c molecule to the initially formed oxidase complex. Kinetic constants so obtained are consistent with the assumption that binding is the dominant parameter in reactivity, and can be rationalized most simply on this basis.", "contents": "Comparative kinetic studies of cytochromes c in reactions with mitochondrial cytochrome c oxidase and reductase. Kinetic studies of the reactions of selected eukaryotic and prokaryotic cytochromes c with mitochondrial cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase (EC 1.9.3.1) using a standardized complex IV preparation from beef heart are reported. Data on reactions with NADH-linked cytochrome c reductase (complexes I and III) are included. The concentration ranges employed provide a basis for quantitative demonstration of a general rate law applicable to oxidase reactions of cytochrome c of greatly differing reactivities. Results are interpreted on the basis of a modified Minnaert mechanism (Minnaert, K. (1961) Biochim. Biophys. Acta 50, 23), assuming productive complex formation between cytochrome c and free oxidase in addition to further complex binding of a second cytochrome c molecule to the initially formed oxidase complex. Kinetic constants so obtained are consistent with the assumption that binding is the dominant parameter in reactivity, and can be rationalized most simply on this basis."}
{"id": "PMID:204338", "title": "Axial ligation and heme environment in cytochrome c-555 from Prosthecochloris aestuarii. Investigation by absorption and solvent perturbation difference spectroscopy.", "content": "The near-IR absorption spectrum indicated that methionine is the sixth axial heme iron ligand in Prosthecochloris aestuarii cytochrome c-555. The heme environment has been investigated by the technique of solvent perturbation difference spectroscopy. The heme octapeptide from cytochrome c plus added imidazole was used as a model compound for the fully exposed chromophore. The heme was found to be minimally exposed to solvent. A comparison was made with cytochrome c, as to the possible causes of the difference in redox potentials betweeen these two cytochromes.", "contents": "Axial ligation and heme environment in cytochrome c-555 from Prosthecochloris aestuarii. Investigation by absorption and solvent perturbation difference spectroscopy. The near-IR absorption spectrum indicated that methionine is the sixth axial heme iron ligand in Prosthecochloris aestuarii cytochrome c-555. The heme environment has been investigated by the technique of solvent perturbation difference spectroscopy. The heme octapeptide from cytochrome c plus added imidazole was used as a model compound for the fully exposed chromophore. The heme was found to be minimally exposed to solvent. A comparison was made with cytochrome c, as to the possible causes of the difference in redox potentials betweeen these two cytochromes."}
{"id": "PMID:204341", "title": "EPR studies of higher plant mitochondria. II. Center S-3 of succinate dehydrogenase and its relation to alternative respiratory oxidations.", "content": "1. An electron paramagnetic resonance study of the high potential iron sulfur (HiPIP-type) Center S-3 of higher plant mitochondria is described. This center is the major HiPIP-type center associated with plant mitochondria and it displays physical properties which are similar to its mammalian counterpart. It has a pH-independent midpoint potential of +65 +/- 10 mV between pH 6.0 and 8.5. 2. The behavior of Center S-3 in a variety of steady-state conditions suggests that it is of physiological significance in electron transport. Furthermore, it can be shown that the alternative oxidase, which is present in many higher plant mitochondria, tends to keep this center oxidized in the presence of succinate and cyanide. This indicates that the alternative oxidation site is on the electron-donating side of the Center S-3. 3. Salicylhydroxamic acid, an inhibitor of the alternative pathway, does not affect the midpoint potential, signal size or shape, or temperature and power saturation profiles of Center S-3, suggesting that direct autoxidation of this center cannot account for alternative oxidase activity. This is further confirmed by the finding that the presence of succinate dehydrogenase is not necessary for alternative oxidase activity with NADH as respiratory substrate in submitochondrial particles.", "contents": "EPR studies of higher plant mitochondria. II. Center S-3 of succinate dehydrogenase and its relation to alternative respiratory oxidations. 1. An electron paramagnetic resonance study of the high potential iron sulfur (HiPIP-type) Center S-3 of higher plant mitochondria is described. This center is the major HiPIP-type center associated with plant mitochondria and it displays physical properties which are similar to its mammalian counterpart. It has a pH-independent midpoint potential of +65 +/- 10 mV between pH 6.0 and 8.5. 2. The behavior of Center S-3 in a variety of steady-state conditions suggests that it is of physiological significance in electron transport. Furthermore, it can be shown that the alternative oxidase, which is present in many higher plant mitochondria, tends to keep this center oxidized in the presence of succinate and cyanide. This indicates that the alternative oxidation site is on the electron-donating side of the Center S-3. 3. Salicylhydroxamic acid, an inhibitor of the alternative pathway, does not affect the midpoint potential, signal size or shape, or temperature and power saturation profiles of Center S-3, suggesting that direct autoxidation of this center cannot account for alternative oxidase activity. This is further confirmed by the finding that the presence of succinate dehydrogenase is not necessary for alternative oxidase activity with NADH as respiratory substrate in submitochondrial particles."}
{"id": "PMID:204343", "title": "Activation of the external pathway of NADH oxidation in liver mitochondria of cold-adapted rats.", "content": "15 min cold exposure of rats adapted to cold results in switching on a pathway of the fast oxidation of extramitochondrial NADH in the isolated liver mitochondria. This pathway is sensitive to mersalyl and cyanide, resistant to amytal and antimycin A, and can be stimulated by dinitrophenol. A portion of the endogenous cytochrome c pool can easily be removed by washing mitochondria of the cold-exposed rats. A scheme is discussed, postulating desorption of the inner membrane-bound cytochrome c into intermembrane space of mitochondria, resulting in formation of a link between the non-phosphorylating NADH-cytochrome c reductase in the outer mitochondrial membrane and cytochrome c oxidase in the inner membrane. It is suggested that such an oxidative pathway is involved in the urgent heat production in liver in response to the cold treatment.", "contents": "Activation of the external pathway of NADH oxidation in liver mitochondria of cold-adapted rats. 15 min cold exposure of rats adapted to cold results in switching on a pathway of the fast oxidation of extramitochondrial NADH in the isolated liver mitochondria. This pathway is sensitive to mersalyl and cyanide, resistant to amytal and antimycin A, and can be stimulated by dinitrophenol. A portion of the endogenous cytochrome c pool can easily be removed by washing mitochondria of the cold-exposed rats. A scheme is discussed, postulating desorption of the inner membrane-bound cytochrome c into intermembrane space of mitochondria, resulting in formation of a link between the non-phosphorylating NADH-cytochrome c reductase in the outer mitochondrial membrane and cytochrome c oxidase in the inner membrane. It is suggested that such an oxidative pathway is involved in the urgent heat production in liver in response to the cold treatment."}
{"id": "PMID:204344", "title": "Redox titrations of cytochrome c oxidase. An analysis of a multi-electron system.", "content": "Equilibrium redox titrations of cytochrome c oxidase available in the literature are discussed in terms of models with interactions both with respect to oxidation-reduction potentials and the particular property studied. 2. The interaction is restricted to be pairwise. For the present data more complicated forms of interaction are not required. In addition, with this limitation a simple matrix formulation can be used. 3. The EPR titrations require potential interaction involving the hemes and the undetectable Cu. In this way the low intensity of the g6 signal can be accounted for. However, it is shown that there is no unique solution to the problem. 4. The optical titrations at 605 nm can be fitted reasonalby well with the potentials from the EPR data with no spectral interaction. 5. Simulated titrations of magnetic susceptibility show a sensitivity to the model chosen indicating the usefulness of future experiments in this area.", "contents": "Redox titrations of cytochrome c oxidase. An analysis of a multi-electron system. Equilibrium redox titrations of cytochrome c oxidase available in the literature are discussed in terms of models with interactions both with respect to oxidation-reduction potentials and the particular property studied. 2. The interaction is restricted to be pairwise. For the present data more complicated forms of interaction are not required. In addition, with this limitation a simple matrix formulation can be used. 3. The EPR titrations require potential interaction involving the hemes and the undetectable Cu. In this way the low intensity of the g6 signal can be accounted for. However, it is shown that there is no unique solution to the problem. 4. The optical titrations at 605 nm can be fitted reasonalby well with the potentials from the EPR data with no spectral interaction. 5. Simulated titrations of magnetic susceptibility show a sensitivity to the model chosen indicating the usefulness of future experiments in this area."}
{"id": "PMID:204346", "title": "On the site of function of the Rieske iron-sulfur center in the chloroplast electron transport chain.", "content": "A photosynthetic mutant (strain 1073) of Lemna perpusilla was previously shown to have a block in the electron transport chain between plastoquinone and cytochrome f ((1976) Plant Physiol. 57, 577--579). Electron paramagnetic resonance analysis of chloroplasts from this mutant indicates that the g = 1.89 signal of a reduced iron-sulfur center (the 'Rieske' iron-sulfur center) is absent. The absence of this signal indicates the Rieske center is either absent from or defective in the mutant, and this result is consistent with this iron-sulfur center functioning between plastoquinone and cytochrome f in the electron transport chain of chloroplasts.", "contents": "On the site of function of the Rieske iron-sulfur center in the chloroplast electron transport chain. A photosynthetic mutant (strain 1073) of Lemna perpusilla was previously shown to have a block in the electron transport chain between plastoquinone and cytochrome f ((1976) Plant Physiol. 57, 577--579). Electron paramagnetic resonance analysis of chloroplasts from this mutant indicates that the g = 1.89 signal of a reduced iron-sulfur center (the 'Rieske' iron-sulfur center) is absent. The absence of this signal indicates the Rieske center is either absent from or defective in the mutant, and this result is consistent with this iron-sulfur center functioning between plastoquinone and cytochrome f in the electron transport chain of chloroplasts."}
{"id": "PMID:204347", "title": "The influence of protein-lipid interactions on the order-disorder conformational transitions of the hydrocarbon chain.", "content": "The phases of simple systems involving one type of protein (lysozyme or cytochrome c) and one type of lipid (phosphatidic acid) have been characterized by X-ray crystallography, chemical analysis and spin-labeling technique as a function of temperature. They are of the lamellar type with alternative protein monolayers and lipid bilayers. According to the pH, two types of lamellar phases are obtained, one where the lipid-protein interactions are mainly hydrophobic, the other where they are electrostatic. In both cases, a phase transition occurs as temperature is lowered, between a high temperature phase, where all the lipids are in the liquid-like state, and another phase where some lipid chains are rigid. In the case of the phases with electrostatic interaction, it is shown that the onset of the order-disorder transition is shifted towards low temperature as compared with the homologous lipid-water phase and that the protein content of the phase decreases as the ratio of the liquid to rigid hydrocarbon chains decreases. This leads us to suggest that in the systems studied in this work the proteins interact only with lipid in the liquid-like state. In the case of the phases with hydrophobic interaction, it is shown that the extent of hydrophobic interaction between protein and lipid increases as the unsaturation of the hydrocarbon chains increases. The onset of the order-disorder transition shows a greater shift towards low temperature than the one observed in the case of the phase with electrostatic interaction.", "contents": "The influence of protein-lipid interactions on the order-disorder conformational transitions of the hydrocarbon chain. The phases of simple systems involving one type of protein (lysozyme or cytochrome c) and one type of lipid (phosphatidic acid) have been characterized by X-ray crystallography, chemical analysis and spin-labeling technique as a function of temperature. They are of the lamellar type with alternative protein monolayers and lipid bilayers. According to the pH, two types of lamellar phases are obtained, one where the lipid-protein interactions are mainly hydrophobic, the other where they are electrostatic. In both cases, a phase transition occurs as temperature is lowered, between a high temperature phase, where all the lipids are in the liquid-like state, and another phase where some lipid chains are rigid. In the case of the phases with electrostatic interaction, it is shown that the onset of the order-disorder transition is shifted towards low temperature as compared with the homologous lipid-water phase and that the protein content of the phase decreases as the ratio of the liquid to rigid hydrocarbon chains decreases. This leads us to suggest that in the systems studied in this work the proteins interact only with lipid in the liquid-like state. In the case of the phases with hydrophobic interaction, it is shown that the extent of hydrophobic interaction between protein and lipid increases as the unsaturation of the hydrocarbon chains increases. The onset of the order-disorder transition shows a greater shift towards low temperature than the one observed in the case of the phase with electrostatic interaction."}
{"id": "PMID:204348", "title": "Interaction between Sendai virus and KB cell lines with altered cell fusion ability: a study employing electron spin resonance.", "content": "The nature of the interaction between Sendai virus and Sil mutant cells was examined by measuring a change in ESR spectrum of spin-labeled phosphatidylcholine molecules on the viral envelope. When spin-labeled virus was incubated with the Sil cells that had a reduced ability to respond to virus-induced cell fusion, interchange of the phospholipid molecules between viral envelope and cell surface membrane occurred to a smaller extent than that observed with parental cells. Moreover, the degree of the interchanging correlated with the degree of the fusion capacity of the mutant lines. The results show that the mutant cells carry such a lesion(s) on their surface membranes that the viral envelopes can hardly fuse into them.", "contents": "Interaction between Sendai virus and KB cell lines with altered cell fusion ability: a study employing electron spin resonance. The nature of the interaction between Sendai virus and Sil mutant cells was examined by measuring a change in ESR spectrum of spin-labeled phosphatidylcholine molecules on the viral envelope. When spin-labeled virus was incubated with the Sil cells that had a reduced ability to respond to virus-induced cell fusion, interchange of the phospholipid molecules between viral envelope and cell surface membrane occurred to a smaller extent than that observed with parental cells. Moreover, the degree of the interchanging correlated with the degree of the fusion capacity of the mutant lines. The results show that the mutant cells carry such a lesion(s) on their surface membranes that the viral envelopes can hardly fuse into them."}
{"id": "PMID:204349", "title": "Cyclic AMP transport in human erythrocyte ghosts.", "content": "10(-5) M cyclic AMP has high permeability in human erythrocyte ghosts (p = 0.061-10(-6) cm.s-1). Saturation of influx and efflux occurs. Koizt = 4.43 mM. Voizt = 259.6 micron.min-1-Kiozt = 0.475 micron. Viozt = 28.3 micron.min-1 at 30 degrees C. Equilibrium exchange entry of cyclic AMP has similar kinetics to zero trans influx, though the system does show counterflow. Cytochalasin B is an apparent competitive inhibitor of cyclic AMP exit. (Ki = 3.9.10(-7) M). Control experiments indicated that cyclic AMP remains intact during incubation with red blood cell ghosts and is contained within the intravesicular space during the transport experiments.", "contents": "Cyclic AMP transport in human erythrocyte ghosts. 10(-5) M cyclic AMP has high permeability in human erythrocyte ghosts (p = 0.061-10(-6) cm.s-1). Saturation of influx and efflux occurs. Koizt = 4.43 mM. Voizt = 259.6 micron.min-1-Kiozt = 0.475 micron. Viozt = 28.3 micron.min-1 at 30 degrees C. Equilibrium exchange entry of cyclic AMP has similar kinetics to zero trans influx, though the system does show counterflow. Cytochalasin B is an apparent competitive inhibitor of cyclic AMP exit. (Ki = 3.9.10(-7) M). Control experiments indicated that cyclic AMP remains intact during incubation with red blood cell ghosts and is contained within the intravesicular space during the transport experiments."}
{"id": "PMID:204351", "title": "Two-component ribonucleotidyl transferase from Escherichia coli. III. Effect of nucleoside diphosphates on synthesis and pyrophosphorolysis of polyribonucleotides by the enzyme.", "content": "1. The capacity of two-component ribonucleotidyl transferase to catalyze pyrophosphorolysis of polyribonucleotides is studied. 2. It is shown that nucleoside diphosphates (NDP), not being substrates for the enzyme, activate both the synthesis and pyrophosphorolysis of polynucleotides by the enzyme. The concentration of NDP is important for this effect: with an increase of NDP concentration the rate of synthesis increases and reaches a plateau at 10(-5) M NDP, while the rate of pyrophosphorolysis, attaining maximal values at 10(-5)--10(-3) M NDP, decreases with a further increase of NDP concentration. 3. The possible biological role of two-component ribonucleotidyl transferase is discussed.", "contents": "Two-component ribonucleotidyl transferase from Escherichia coli. III. Effect of nucleoside diphosphates on synthesis and pyrophosphorolysis of polyribonucleotides by the enzyme. 1. The capacity of two-component ribonucleotidyl transferase to catalyze pyrophosphorolysis of polyribonucleotides is studied. 2. It is shown that nucleoside diphosphates (NDP), not being substrates for the enzyme, activate both the synthesis and pyrophosphorolysis of polynucleotides by the enzyme. The concentration of NDP is important for this effect: with an increase of NDP concentration the rate of synthesis increases and reaches a plateau at 10(-5) M NDP, while the rate of pyrophosphorolysis, attaining maximal values at 10(-5)--10(-3) M NDP, decreases with a further increase of NDP concentration. 3. The possible biological role of two-component ribonucleotidyl transferase is discussed."}
{"id": "PMID:204352", "title": "On the mechanism of the acceleration of methanesulfonylation of acetylcholinesterase with cationic accelerators.", "content": "1. In order to elucidate some features of the mechanism of the acceleration of methanesulfonylation of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) with cationic accelerators, the methanesulfonylation of this enzyme by high concentrations of methanesulfonylfluoride, in the absence and presence of accelerators decamethonium and tetraethylammonium, was studied. 2. The results showed that the accelerator accelerates the reaction by electrostatically improving the binding between acetylcholinesterase and methanesulfonylfluoride without effecting the rate of the decomposition of the enzyme-inhibitor complex into the methanesulfonylated enzyme and product.", "contents": "On the mechanism of the acceleration of methanesulfonylation of acetylcholinesterase with cationic accelerators. 1. In order to elucidate some features of the mechanism of the acceleration of methanesulfonylation of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) with cationic accelerators, the methanesulfonylation of this enzyme by high concentrations of methanesulfonylfluoride, in the absence and presence of accelerators decamethonium and tetraethylammonium, was studied. 2. The results showed that the accelerator accelerates the reaction by electrostatically improving the binding between acetylcholinesterase and methanesulfonylfluoride without effecting the rate of the decomposition of the enzyme-inhibitor complex into the methanesulfonylated enzyme and product."}
{"id": "PMID:204353", "title": "Comparison of two forms of pig heart phosphoprotein phosphatase.", "content": "A phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) was partially purified from pig heart using as substrate H2B histone which had been phosphorylated at Ser-32 and Ser-36 by adenosine 3',5'-monophosphate-dependent protein kinase (EC 2.7.1.37). The enzyme had a molecular weight of approx. 250 000 and was converted to a smaller form with a molecular weight of approx. 30 000 upon treatment with ethanol. Phosphorylase alpha (EC 2.4.1.1) and phosphorylated H1 histone also served as substrates for both forms of the enzyme. The conversion of the large form of the enzyme to the small form decreased the phosphohistone phosphatase activity to 25-50% with a concomitant 7-fold increase in the phosphorylase alpha phosphatase activity. Ser-36 phosphate was removed 6- and 15-fold more rapidly than was Ser-32 phosphate by the large and small forms of the enzyme, respectively. Among Ser-36-containing tryptic phosphopeptides derived from phosphorylated H2B histone, Lys-Glu-Ser(P)-Tyr-Ser-Val-Tyr was the shortest phosphopeptide which was dephosphorylated at a significant reaction rate with the phosphoprotein phosphatase. The Km values for phosphorylated H2B histone and the tryptic phosphopeptide were 23.7 micron and 187.1 micron, respectively, with the large form, and 81.4 micron and 90.0 micron, respectively, with the small form of the enzyme.", "contents": "Comparison of two forms of pig heart phosphoprotein phosphatase. A phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) was partially purified from pig heart using as substrate H2B histone which had been phosphorylated at Ser-32 and Ser-36 by adenosine 3',5'-monophosphate-dependent protein kinase (EC 2.7.1.37). The enzyme had a molecular weight of approx. 250 000 and was converted to a smaller form with a molecular weight of approx. 30 000 upon treatment with ethanol. Phosphorylase alpha (EC 2.4.1.1) and phosphorylated H1 histone also served as substrates for both forms of the enzyme. The conversion of the large form of the enzyme to the small form decreased the phosphohistone phosphatase activity to 25-50% with a concomitant 7-fold increase in the phosphorylase alpha phosphatase activity. Ser-36 phosphate was removed 6- and 15-fold more rapidly than was Ser-32 phosphate by the large and small forms of the enzyme, respectively. Among Ser-36-containing tryptic phosphopeptides derived from phosphorylated H2B histone, Lys-Glu-Ser(P)-Tyr-Ser-Val-Tyr was the shortest phosphopeptide which was dephosphorylated at a significant reaction rate with the phosphoprotein phosphatase. The Km values for phosphorylated H2B histone and the tryptic phosphopeptide were 23.7 micron and 187.1 micron, respectively, with the large form, and 81.4 micron and 90.0 micron, respectively, with the small form of the enzyme."}
{"id": "PMID:204354", "title": "Phosphoprotein phosphatase in bovine tracheal smooth muscle. Multiple fractions and multiple substrates.", "content": "Phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) from bovine tracheal smooth muscle extracts was isolated and its activity determined using two [32P]phosphorylated proteins as substrates, i.e. phosphorylated histone (H-P) and a phosphorylated muscle specific substrate protein (MS-P) for the tracheal smooth muscle protein kinase. The enzyme was purified by the use of DEAE-cellulose followed by a two stage chromatography on a histone-Sepharose affinity column. Elution from the affinity column resolved the phosphoprotein phosphatase into four activity fractions. While fractions expressed phosphatase activity against both tested substrates the relative amounts of either activity varied. The ratio of activity towards H-P to activity towards MS-P changed from 11.5 to 0.12. The characterization of four phosphoprotein phosphatase fractions was based on the differences found in the following parameters: substrate specificity; sensitivity to NaF; influences of nucleotides (ATP, 5'-AMP, cyclic AMP, cyclic GMP) and the requirement of Mn2+ for maximal activity. Mg2+, Ba2+ or Ca2+ could not substitute for Mn2+.", "contents": "Phosphoprotein phosphatase in bovine tracheal smooth muscle. Multiple fractions and multiple substrates. Phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) from bovine tracheal smooth muscle extracts was isolated and its activity determined using two [32P]phosphorylated proteins as substrates, i.e. phosphorylated histone (H-P) and a phosphorylated muscle specific substrate protein (MS-P) for the tracheal smooth muscle protein kinase. The enzyme was purified by the use of DEAE-cellulose followed by a two stage chromatography on a histone-Sepharose affinity column. Elution from the affinity column resolved the phosphoprotein phosphatase into four activity fractions. While fractions expressed phosphatase activity against both tested substrates the relative amounts of either activity varied. The ratio of activity towards H-P to activity towards MS-P changed from 11.5 to 0.12. The characterization of four phosphoprotein phosphatase fractions was based on the differences found in the following parameters: substrate specificity; sensitivity to NaF; influences of nucleotides (ATP, 5'-AMP, cyclic AMP, cyclic GMP) and the requirement of Mn2+ for maximal activity. Mg2+, Ba2+ or Ca2+ could not substitute for Mn2+."}
{"id": "PMID:204355", "title": "NAD recycling in the collagen membrane.", "content": "NAD recycling in the collagen membrane was investigated as follows: (1) Alcohol dehydrogenase and lactate dehydrogenase were co-immobilized in the collagen membrane and the rate of lactate production by immobilized enzymes was compared with that of free enzymes by using free NAD. An increased rate was observed in the case of immobilized enzyme. (2) The soluble high molecular weight derivatives of NAD (dextran-NAD) were immobilized in the collagen membrane with the two dehydrogenases and recycling of dextran-NAD in the membrane was examined. Lactate was produced by the membrane without adding free NAD. The interaction between the high molecular weight NAD derivatives and enzymes are also discussed.", "contents": "NAD recycling in the collagen membrane. NAD recycling in the collagen membrane was investigated as follows: (1) Alcohol dehydrogenase and lactate dehydrogenase were co-immobilized in the collagen membrane and the rate of lactate production by immobilized enzymes was compared with that of free enzymes by using free NAD. An increased rate was observed in the case of immobilized enzyme. (2) The soluble high molecular weight derivatives of NAD (dextran-NAD) were immobilized in the collagen membrane with the two dehydrogenases and recycling of dextran-NAD in the membrane was examined. Lactate was produced by the membrane without adding free NAD. The interaction between the high molecular weight NAD derivatives and enzymes are also discussed."}
{"id": "PMID:204356", "title": "Purification and properties of a nucleoside diphosphosugar: NAD+ 2-hexosyl oxidoreductase.", "content": "Penicillium charlesii contains a nucleoside diphosphosugar: NAD 2-hexosyl oxidoreductase that oxidizes UDPgalactose (UDP-Galp), ADPribose [1,2] and UDPglucose (UDP-Glc). Dithiothreitol, NAD and 0.25 M NaCl but not nucleoside diphosphates stabilize the enzyme activity. The enzyme was purified and separated on polyacrylamide disc gels by electrophoresis into one major and eight minor bands of protein. Oxidoreductase activity was located in the major and three of the minor bands of protein. Each of these proteins catalyze the oxidation of UDPGalp, ADPribose and UDP-Glc.", "contents": "Purification and properties of a nucleoside diphosphosugar: NAD+ 2-hexosyl oxidoreductase. Penicillium charlesii contains a nucleoside diphosphosugar: NAD 2-hexosyl oxidoreductase that oxidizes UDPgalactose (UDP-Galp), ADPribose [1,2] and UDPglucose (UDP-Glc). Dithiothreitol, NAD and 0.25 M NaCl but not nucleoside diphosphates stabilize the enzyme activity. The enzyme was purified and separated on polyacrylamide disc gels by electrophoresis into one major and eight minor bands of protein. Oxidoreductase activity was located in the major and three of the minor bands of protein. Each of these proteins catalyze the oxidation of UDPGalp, ADPribose and UDP-Glc."}
{"id": "PMID:204359", "title": "The parotid gland: a new target organ for vitamin D action.", "content": "Radioactively labelled cholecalciferol was administered continuously to rats which were fed a vitamin D-deficient diet. It has been possible to show that all the metabolites of the cholecalciferol which normally occur in known target tissues of vitamin D are present in the parotid gland, and the pattern resembled that obtained for the kidney, a known target tissue for vitamin D action. The accumulation of cholecalciferol metabolites in the parotid gland was shown to be functional, as a calcium-binding protein was found to be present in the gland, possessing similar properties to the renal vitamin D-dependent calcium-binding protein.", "contents": "The parotid gland: a new target organ for vitamin D action. Radioactively labelled cholecalciferol was administered continuously to rats which were fed a vitamin D-deficient diet. It has been possible to show that all the metabolites of the cholecalciferol which normally occur in known target tissues of vitamin D are present in the parotid gland, and the pattern resembled that obtained for the kidney, a known target tissue for vitamin D action. The accumulation of cholecalciferol metabolites in the parotid gland was shown to be functional, as a calcium-binding protein was found to be present in the gland, possessing similar properties to the renal vitamin D-dependent calcium-binding protein."}
{"id": "PMID:204360", "title": "Cyclic AMP-induced enhancement of calcium accumulation by the sarcoplasmic reticulum with no modification of the sensitivity of the myofilaments to calcium in skinned fibres from a yeast skeletal muscle.", "content": "In the presence of low concentrations of total EGTA (5 . 10(-4) M) and free Mg2+ (3.16 . 10(-5) M) and in the presence of caffeine (8 . 10(-3) M), cyclic AMP (5 . 10(-6) M) produces a relaxation of the tension developed by skinned fibres from cat caudo-femoralis. The relaxation can be attributed to an enhancement of the Ca2+ accumulation by the sarcoplasmic reticulum, since cyclic AMP does not modify the sensitivity of the myofilaments of Ca2+. These results are similar to those previously reported for the effect of cyclic AMP on skinned cardiac cells in the presence of a higher free Mg2+ concentration and in the absence of caffeine. This similarity suggests that the mode of action of cyclic AMP on the sarcoplasmic reticulum is not fundamentally different in cardiac and fast skeletal muscles.", "contents": "Cyclic AMP-induced enhancement of calcium accumulation by the sarcoplasmic reticulum with no modification of the sensitivity of the myofilaments to calcium in skinned fibres from a yeast skeletal muscle. In the presence of low concentrations of total EGTA (5 . 10(-4) M) and free Mg2+ (3.16 . 10(-5) M) and in the presence of caffeine (8 . 10(-3) M), cyclic AMP (5 . 10(-6) M) produces a relaxation of the tension developed by skinned fibres from cat caudo-femoralis. The relaxation can be attributed to an enhancement of the Ca2+ accumulation by the sarcoplasmic reticulum, since cyclic AMP does not modify the sensitivity of the myofilaments of Ca2+. These results are similar to those previously reported for the effect of cyclic AMP on skinned cardiac cells in the presence of a higher free Mg2+ concentration and in the absence of caffeine. This similarity suggests that the mode of action of cyclic AMP on the sarcoplasmic reticulum is not fundamentally different in cardiac and fast skeletal muscles."}
{"id": "PMID:204362", "title": "Energy requirements for the action of staphylococcin 1580 in Staphyloccus aureus.", "content": "1. Starved cells of a glucose-grown strain of Staphylococcus aureus are resistant to the action of staphylococcin 1580. Reinitiation of sensitivity is readily obtained upon the addition of glucose, but only weakly with L-lactate, although the latter induces higher ATP levels and supports L-glutamic acid uptake better than glucose does. The NADH/NAD+ ratio correlates with the staphylococcin sensitivity. 2. Starved pyruvate-grown cells remain partially susceptible and full sensitivity is restored both in the presence of glucose and L-lactate. 3. Arsenate but not dicyclohexylcarbodiimide (DCCD) blocks the reinitiation of sensitivity in the presence of glucose. Both arsenate and DCCD block sensitivity in the presence of L-lactate. 4. Aerobically grown cells are sensitive to staphylococcin 1580 under anaerobic conditions. Anaerobically grown cells are less susceptible, but sensitivity can be restored by glucose and also by L-lactate plus nitrate when cells are previously induced for nitrate reductase. 5. Starved cells of a mutant strain defective in the maintenance of a high-energy state of the membrane are normally sensitive in the presence of glucose, but resistant in the presence of L-lactate. A strain lacking a functional respiratory chain (men-) is also sensitive with glucose but resistant in the presence of L-lactate. 6. It is concluded that the initiation of the staphylococcin 1580 action is under control of a mechanism regulating the energy flow in the cell, and involving the presence of a high-energy phosphorylated compound.", "contents": "Energy requirements for the action of staphylococcin 1580 in Staphyloccus aureus. 1. Starved cells of a glucose-grown strain of Staphylococcus aureus are resistant to the action of staphylococcin 1580. Reinitiation of sensitivity is readily obtained upon the addition of glucose, but only weakly with L-lactate, although the latter induces higher ATP levels and supports L-glutamic acid uptake better than glucose does. The NADH/NAD+ ratio correlates with the staphylococcin sensitivity. 2. Starved pyruvate-grown cells remain partially susceptible and full sensitivity is restored both in the presence of glucose and L-lactate. 3. Arsenate but not dicyclohexylcarbodiimide (DCCD) blocks the reinitiation of sensitivity in the presence of glucose. Both arsenate and DCCD block sensitivity in the presence of L-lactate. 4. Aerobically grown cells are sensitive to staphylococcin 1580 under anaerobic conditions. Anaerobically grown cells are less susceptible, but sensitivity can be restored by glucose and also by L-lactate plus nitrate when cells are previously induced for nitrate reductase. 5. Starved cells of a mutant strain defective in the maintenance of a high-energy state of the membrane are normally sensitive in the presence of glucose, but resistant in the presence of L-lactate. A strain lacking a functional respiratory chain (men-) is also sensitive with glucose but resistant in the presence of L-lactate. 6. It is concluded that the initiation of the staphylococcin 1580 action is under control of a mechanism regulating the energy flow in the cell, and involving the presence of a high-energy phosphorylated compound."}
{"id": "PMID:204363", "title": "A precursor in the photolytic cleavage of the Co (III)-C bond of coenzyme B-12 unobservable by electron paramagnetic resonance.", "content": "Photolysis of a frozen (80--200 K) anaerobic solution of 5'-deoxyadenosyl-cobalamin in aqueous propan-1,2-diol produces only a small Co(II) signal detectable by electron paramagnetic resonance (EPR). Upon warming to room temperature and refreezing without further irradiation the Co(II) signal increases many-fold. The interpretation is that at low temperature there is an EPR-undetectable \"incipient\" homolysis of the Co-C bond of the coenzyme which is revealed at higher temperature. The possible implications of this observation for the coenzyme B-12-dependent enzymes are noted.", "contents": "A precursor in the photolytic cleavage of the Co (III)-C bond of coenzyme B-12 unobservable by electron paramagnetic resonance. Photolysis of a frozen (80--200 K) anaerobic solution of 5'-deoxyadenosyl-cobalamin in aqueous propan-1,2-diol produces only a small Co(II) signal detectable by electron paramagnetic resonance (EPR). Upon warming to room temperature and refreezing without further irradiation the Co(II) signal increases many-fold. The interpretation is that at low temperature there is an EPR-undetectable \"incipient\" homolysis of the Co-C bond of the coenzyme which is revealed at higher temperature. The possible implications of this observation for the coenzyme B-12-dependent enzymes are noted."}
{"id": "PMID:204366", "title": "A model of quick phase generation in the vestibuloocular reflex.", "content": "The vestibuloocular relfex of the cat was studied during step and sinusoidal head velocity stimuli. A model is presented which simulates the observed slow phase and quick phase behavior. The model is constructed to be compatible with neurophysiological observations of the behavior of neurons in the pons. Emphasis is placed on the amplitude and timing of quick phases which are active orienting movements that drive the eyes into the direction of turning. It is proposed that quick phases, like saccades, are generated by a local feedback loop in the pons which rapidly drives the eyes to a point in the orbit specified by a vestibular signal. It is suggested that two internal signals specify the eye positions at which quick phases start and end. The statistics of the fluctuations of these signals was measured and correlation between them was discovered and incorporated in the model.", "contents": "A model of quick phase generation in the vestibuloocular reflex. The vestibuloocular relfex of the cat was studied during step and sinusoidal head velocity stimuli. A model is presented which simulates the observed slow phase and quick phase behavior. The model is constructed to be compatible with neurophysiological observations of the behavior of neurons in the pons. Emphasis is placed on the amplitude and timing of quick phases which are active orienting movements that drive the eyes into the direction of turning. It is proposed that quick phases, like saccades, are generated by a local feedback loop in the pons which rapidly drives the eyes to a point in the orbit specified by a vestibular signal. It is suggested that two internal signals specify the eye positions at which quick phases start and end. The statistics of the fluctuations of these signals was measured and correlation between them was discovered and incorporated in the model."}
{"id": "PMID:204369", "title": "Electron spin polarization in photosynthesis and the mechanism of electron transfer in photosystem I. Experimental observations.", "content": "Transient electron paramagnetic resonance (EPR) methods are used to examine the spin populations of the light-induced radicals produced in spinach chloroplasts, photosystem I particles, and Chlorella pyrenoidosa. We observe both emission and enhanced absorption within the hyperfine structure of the EPR spectrum of P700+, the photooxidized reaction-center chlorophyll radical (Signal I). By using flow gradients or magnetic fields to orient the chloroplasts in the Zeeman field, we are able to influence both the magnitude and sign of the spin polarization. Identification of the polarized radical and P700+ is consistent with the effects of inhibitors, excitation light intensity and wavelength, redox potential, and fractionation of the membranes. The EPR signal of the polarized P700+ radical displays a 30% narrower line width than P700+ after spin relaxation. This suggests a magnetic interaction between P700+ and its reduced (paramagnetic) acceptor, which leads to a collapse of the P700+ hyperfine structure. Narrowing of the spectrum is evident only in the spectrum of polarized P700+, because prompt electron transfer rapidly separates the radical pair. Evidence of cross-relaxation between the adjacent radicals suggests the existence of an exchange interaction. The results indicate that polarization is produced by a radical pair mechanism between P700+ and the reduced primary acceptor of photosystem I. The orientation dependence of the spin polarization of P700+ is due to the g-tensor anisotropy of the acceptor radical to which it is exchange-coupled. The EPR spectrum of P700+ is virtually isotropic once the adjacent acceptor radical has passed the photoionized electron to a later, more remote acceptor molecule. This interpretation implies that the acceptor radical has g-tensor anisotropy significantly greater than the width of the hyperfine field on P700+ and that the acceptor is oriented with its smallest g-tensor axis along the normal to the thylakoid membranes. Both the ferredoxin-like iron-sulfur centers and the X- species observed directly by EPR at low temperatures have g-tensor anisotropy large enough to produce the observed spin polarization; however, studies on oriented chloroplasts show that the bound ferredoxin centers do not have this orientation of their g tensors. In contrast, X- is aligned with its smallest g-tensor axis predominantly normal to the plane of the thylakoid membranes. This is the same orientation predicted for the acceptor radical based on analysis of the spin polarization of P700+, and indicates that the species responsible for the anisotropy of the polarized P700+ spectrum is probably X-. The dark EPR Signal II is shown to possess anisotropic hyperfine structure (and possibly g-tensor anisotropy), which serves as a good indicator of the extent of membrane alignment.", "contents": "Electron spin polarization in photosynthesis and the mechanism of electron transfer in photosystem I. Experimental observations. Transient electron paramagnetic resonance (EPR) methods are used to examine the spin populations of the light-induced radicals produced in spinach chloroplasts, photosystem I particles, and Chlorella pyrenoidosa. We observe both emission and enhanced absorption within the hyperfine structure of the EPR spectrum of P700+, the photooxidized reaction-center chlorophyll radical (Signal I). By using flow gradients or magnetic fields to orient the chloroplasts in the Zeeman field, we are able to influence both the magnitude and sign of the spin polarization. Identification of the polarized radical and P700+ is consistent with the effects of inhibitors, excitation light intensity and wavelength, redox potential, and fractionation of the membranes. The EPR signal of the polarized P700+ radical displays a 30% narrower line width than P700+ after spin relaxation. This suggests a magnetic interaction between P700+ and its reduced (paramagnetic) acceptor, which leads to a collapse of the P700+ hyperfine structure. Narrowing of the spectrum is evident only in the spectrum of polarized P700+, because prompt electron transfer rapidly separates the radical pair. Evidence of cross-relaxation between the adjacent radicals suggests the existence of an exchange interaction. The results indicate that polarization is produced by a radical pair mechanism between P700+ and the reduced primary acceptor of photosystem I. The orientation dependence of the spin polarization of P700+ is due to the g-tensor anisotropy of the acceptor radical to which it is exchange-coupled. The EPR spectrum of P700+ is virtually isotropic once the adjacent acceptor radical has passed the photoionized electron to a later, more remote acceptor molecule. This interpretation implies that the acceptor radical has g-tensor anisotropy significantly greater than the width of the hyperfine field on P700+ and that the acceptor is oriented with its smallest g-tensor axis along the normal to the thylakoid membranes. Both the ferredoxin-like iron-sulfur centers and the X- species observed directly by EPR at low temperatures have g-tensor anisotropy large enough to produce the observed spin polarization; however, studies on oriented chloroplasts show that the bound ferredoxin centers do not have this orientation of their g tensors. In contrast, X- is aligned with its smallest g-tensor axis predominantly normal to the plane of the thylakoid membranes. This is the same orientation predicted for the acceptor radical based on analysis of the spin polarization of P700+, and indicates that the species responsible for the anisotropy of the polarized P700+ spectrum is probably X-. The dark EPR Signal II is shown to possess anisotropic hyperfine structure (and possibly g-tensor anisotropy), which serves as a good indicator of the extent of membrane alignment."}
{"id": "PMID:204375", "title": "[Concentration of free fatty acids in muscle following administration of corticotropin and hydrocortisone].", "content": "Experiments were conducted on rats; the gas chromatographic method was applied to the study of the free fatty acids content in the gastrocnemius 30 minutes after the intraperitoneal injection of adrenocorticotropic hormone (ACTH)--1 Unit per 100 g and hydrocortisone acetate--1 mg per 100 gm of body weight. It was shown that in the resting muscles ACTH increased the content of stearic acid, whereas hydrocortisone--of both stearic oleic acids. The changes in the content of other free fatty acids were insignificant. During the short-term activity the content of stearic acid in the regimen of single rhythmic contractions in the gastrocnemius of intact rats increased. In experiments with ACTH and hydrocortisone this elevation was much less and not significant. ACTH and hydrocortisone stimulated the stearic acid consumption by the muscles during the activity.", "contents": "[Concentration of free fatty acids in muscle following administration of corticotropin and hydrocortisone]. Experiments were conducted on rats; the gas chromatographic method was applied to the study of the free fatty acids content in the gastrocnemius 30 minutes after the intraperitoneal injection of adrenocorticotropic hormone (ACTH)--1 Unit per 100 g and hydrocortisone acetate--1 mg per 100 gm of body weight. It was shown that in the resting muscles ACTH increased the content of stearic acid, whereas hydrocortisone--of both stearic oleic acids. The changes in the content of other free fatty acids were insignificant. During the short-term activity the content of stearic acid in the regimen of single rhythmic contractions in the gastrocnemius of intact rats increased. In experiments with ACTH and hydrocortisone this elevation was much less and not significant. ACTH and hydrocortisone stimulated the stearic acid consumption by the muscles during the activity."}
{"id": "PMID:204376", "title": "[Post-radiation disorders in the cyclic AMP system of mouse spleen and thymus lymphoid cells].", "content": "Early alterations in the enzyme activities controlling cyclic adenosine-3',5'-monophosphate (cAMP) metabolism after the irradiation (800 rad) of mice were found in the lymphoid cells of the spleen and thymus. Postradiation disturbances in these activities' ration induced alterations in cAMP steady-state concentrations in the cell. It was also demonstrated that irradiation reduced lymphoid cell ability to accumulate cAMP in response to isoproterenol administration.", "contents": "[Post-radiation disorders in the cyclic AMP system of mouse spleen and thymus lymphoid cells]. Early alterations in the enzyme activities controlling cyclic adenosine-3',5'-monophosphate (cAMP) metabolism after the irradiation (800 rad) of mice were found in the lymphoid cells of the spleen and thymus. Postradiation disturbances in these activities' ration induced alterations in cAMP steady-state concentrations in the cell. It was also demonstrated that irradiation reduced lymphoid cell ability to accumulate cAMP in response to isoproterenol administration."}
{"id": "PMID:204377", "title": "[Effect of colchamine on Ehrlich ascitic carcinoma cells showing synchronized cell division].", "content": "The author studied the 24-hour changes in the number of normal and colchamine mitoses in the cells of Ehrlich's ascites carcinoma in mice after the injection of colchamine argainst the background of partial synchronization of cell division, obtained as a result of preliminary injection of dibutyryl cyclic 3',5'-AMP, and also in mice after the injection of colchamine alone or dibutyryl cyclic 3',5'-AMP. As shown, synchronization of cell division in the tumour led to the 2,6-fold increase in the number of tumour cells blocked by colchamine and also to the accelerated arrest of colchamine mitoses.", "contents": "[Effect of colchamine on Ehrlich ascitic carcinoma cells showing synchronized cell division]. The author studied the 24-hour changes in the number of normal and colchamine mitoses in the cells of Ehrlich's ascites carcinoma in mice after the injection of colchamine argainst the background of partial synchronization of cell division, obtained as a result of preliminary injection of dibutyryl cyclic 3',5'-AMP, and also in mice after the injection of colchamine alone or dibutyryl cyclic 3',5'-AMP. As shown, synchronization of cell division in the tumour led to the 2,6-fold increase in the number of tumour cells blocked by colchamine and also to the accelerated arrest of colchamine mitoses."}
{"id": "PMID:204378", "title": "[Effect of thyroliberin (thyrotropin-releasing-hormone) on secretion of thyrotropic hormone and prolacting in a monolayer cultrue of rat adenohypophysis].", "content": "Cells of the adenohypophysis in the primary 5--8 day monolayer culture responded to the administration of the thyrotropin-releasing-hormone (TRH) by a rapid dose-dependent release of thyrotropic hormone (TTH) and prolactin into the culture medium. This effect is independent of the serum content in the nutrient medium. Thyroxin, the thyroid gland hormone, blocks the stimulating action of TRH with respect to the TTH secretion, but not to prolactin. The blocking effect of thyroxin is apparently expressed not on the cell membranes, but in the cytoplasm, distal to cAMP, by way of the hormonal signal transmission.", "contents": "[Effect of thyroliberin (thyrotropin-releasing-hormone) on secretion of thyrotropic hormone and prolacting in a monolayer cultrue of rat adenohypophysis]. Cells of the adenohypophysis in the primary 5--8 day monolayer culture responded to the administration of the thyrotropin-releasing-hormone (TRH) by a rapid dose-dependent release of thyrotropic hormone (TTH) and prolactin into the culture medium. This effect is independent of the serum content in the nutrient medium. Thyroxin, the thyroid gland hormone, blocks the stimulating action of TRH with respect to the TTH secretion, but not to prolactin. The blocking effect of thyroxin is apparently expressed not on the cell membranes, but in the cytoplasm, distal to cAMP, by way of the hormonal signal transmission."}
{"id": "PMID:204379", "title": "[Comparative study of several structuro-functional parameters of the liver and adrenal cortex in mice of different genetic strains under physiologically normal conditions].", "content": "In adult male mice CBA and C57BL there were revealed differences in the morphometric characteristics of the subcellular organization of hepatocytes, as well as in the indices of functional capacity of the adrenal cortex and the rate of metabolism of steroid hormones in the liver. In animals of the strains under study the levels of steroid hormones production by the adrenal cortex and the rate of gross metabolism of steroid hormones in the liver were characterized by inverse relationship. Structural-functional indices of the adrenal cortex and the liver are supposed to cause different liver responses in these strains of mice to the influence of the alterating factors.", "contents": "[Comparative study of several structuro-functional parameters of the liver and adrenal cortex in mice of different genetic strains under physiologically normal conditions]. In adult male mice CBA and C57BL there were revealed differences in the morphometric characteristics of the subcellular organization of hepatocytes, as well as in the indices of functional capacity of the adrenal cortex and the rate of metabolism of steroid hormones in the liver. In animals of the strains under study the levels of steroid hormones production by the adrenal cortex and the rate of gross metabolism of steroid hormones in the liver were characterized by inverse relationship. Structural-functional indices of the adrenal cortex and the liver are supposed to cause different liver responses in these strains of mice to the influence of the alterating factors."}
{"id": "PMID:204380", "title": "Response of blood vessels to sympathetic nerve stimulation.", "content": "The frequency response curves (FRC) of isolated blood vessels differ from each other not only in their initial slopes, but in their maxima, and their intercept on the frequency axis. Within the physiological range, there is a linear relation between response and frequency. The FRC of most vessels with junctional innervation are similar, varying only somewhat with innervation density. Other factors found to influence the FRC are: variation in innervation distribution, in the extent of myogenic propragation, and large differences in the sensitivity of the alpha-adrenergic receptor. The effectiveness of the transmitter increases with frequency rise. The maximum effective radius of the transmitter released from one varicosity is only several microns. In vessels with light to moderate innervation density at low frequencies, there is probably little overlap of transmitter effect from adjacent varicosities even at the outermost layers of smooth muscle cells. There is a disparity between neurogenic response and that which might be expected from the direct action of the transmitter. It is proposed that a local limited myogenic extension of excitation may extend the local action of a quantum of transmitter.", "contents": "Response of blood vessels to sympathetic nerve stimulation. The frequency response curves (FRC) of isolated blood vessels differ from each other not only in their initial slopes, but in their maxima, and their intercept on the frequency axis. Within the physiological range, there is a linear relation between response and frequency. The FRC of most vessels with junctional innervation are similar, varying only somewhat with innervation density. Other factors found to influence the FRC are: variation in innervation distribution, in the extent of myogenic propragation, and large differences in the sensitivity of the alpha-adrenergic receptor. The effectiveness of the transmitter increases with frequency rise. The maximum effective radius of the transmitter released from one varicosity is only several microns. In vessels with light to moderate innervation density at low frequencies, there is probably little overlap of transmitter effect from adjacent varicosities even at the outermost layers of smooth muscle cells. There is a disparity between neurogenic response and that which might be expected from the direct action of the transmitter. It is proposed that a local limited myogenic extension of excitation may extend the local action of a quantum of transmitter."}
{"id": "PMID:204381", "title": "Modes of vasoconstrictor and vasodilator neurotransmission.", "content": "Vasoconstrictor and vasodilator neuroeffector transmission occurs in a variety of modes. Models are presented depicting vascular segments under the direct control of a single or multiple innervation, or an indirect influence via secondary release of a vasoactive substance. The neuroeffector relationship in the rabbit portal vein is described to illustrate the coexistence of several modes of transmission. ATP or its congener is released from the nonadrenergic vasodilator nerves in this vein, possibly as the transmitter. Further, a similar substance is released from the adrenergic vasoconstrictor nerves. It possibly acts directly on smooth muscle cells to relax them, and on the nerve terminals to inhibit the adrenergic transmitter release. Evidence suggests that such purine-mediated feedback mechanism may also occur at many other adrenergic and nonadrenergic neuroeffector synapses.", "contents": "Modes of vasoconstrictor and vasodilator neurotransmission. Vasoconstrictor and vasodilator neuroeffector transmission occurs in a variety of modes. Models are presented depicting vascular segments under the direct control of a single or multiple innervation, or an indirect influence via secondary release of a vasoactive substance. The neuroeffector relationship in the rabbit portal vein is described to illustrate the coexistence of several modes of transmission. ATP or its congener is released from the nonadrenergic vasodilator nerves in this vein, possibly as the transmitter. Further, a similar substance is released from the adrenergic vasoconstrictor nerves. It possibly acts directly on smooth muscle cells to relax them, and on the nerve terminals to inhibit the adrenergic transmitter release. Evidence suggests that such purine-mediated feedback mechanism may also occur at many other adrenergic and nonadrenergic neuroeffector synapses."}
{"id": "PMID:204382", "title": "Relationship between noradrenaline-induced depolarization and contraction in vascular smooth muscle.", "content": "In strips of rabbit main pulmonary artery, full dose-response curves of noradrenaline for the mechanical and electrical responses of the vascular smooth muscle cells were obtained under normal conditions and after increasing and decreasing the membrane potential with strychnine and tetraethylammonium, respectively. The results suggest that the magnitude of the noradrenaline-induced contraction is related to the height of the membrane potential and not to the degree of depolarization produced by the adrenergic transmitter.", "contents": "Relationship between noradrenaline-induced depolarization and contraction in vascular smooth muscle. In strips of rabbit main pulmonary artery, full dose-response curves of noradrenaline for the mechanical and electrical responses of the vascular smooth muscle cells were obtained under normal conditions and after increasing and decreasing the membrane potential with strychnine and tetraethylammonium, respectively. The results suggest that the magnitude of the noradrenaline-induced contraction is related to the height of the membrane potential and not to the degree of depolarization produced by the adrenergic transmitter."}
{"id": "PMID:204383", "title": "Involvement of calcium in cyclic nucleotide metabolism in human vascular smooth muscle.", "content": "When cyclic nucleotide phosphodiesterase was purified from isolated smooth muscle layer of human aorta by DEAE-cellulose column chromatography, separated cyclic GMP phosphodiesterase activity was markedly stimulated in the presence of 10-20 micrometer of Ca2+ by a protein modulator which has similar physicochemical properties to troponin C. Synthetic compound, N-(6-aminohexl)-5-chloro-1-naphthalensulfonamide, which produced relaxations of arteries contracted by prostaglandin F2alpha or KCl was found to inhibit selectively this Ca2+-dependent cyclic GMP phosphodiesterase. This compound produced inhibition of superprecipitation of myosin B system obtained from mouse skeletal muscle and also inhibited adenosine triphosphatase activity of myosin B. Our data suggest that calcium is involved through a protein modulator in cyclic nucleotide metabolism of vascular smooth muscle and that the calcium-dependent protein modulator probably participates in the regulation of contractile response of vascular smooth muscle by affecting actomyosin ATPase activity.", "contents": "Involvement of calcium in cyclic nucleotide metabolism in human vascular smooth muscle. When cyclic nucleotide phosphodiesterase was purified from isolated smooth muscle layer of human aorta by DEAE-cellulose column chromatography, separated cyclic GMP phosphodiesterase activity was markedly stimulated in the presence of 10-20 micrometer of Ca2+ by a protein modulator which has similar physicochemical properties to troponin C. Synthetic compound, N-(6-aminohexl)-5-chloro-1-naphthalensulfonamide, which produced relaxations of arteries contracted by prostaglandin F2alpha or KCl was found to inhibit selectively this Ca2+-dependent cyclic GMP phosphodiesterase. This compound produced inhibition of superprecipitation of myosin B system obtained from mouse skeletal muscle and also inhibited adenosine triphosphatase activity of myosin B. Our data suggest that calcium is involved through a protein modulator in cyclic nucleotide metabolism of vascular smooth muscle and that the calcium-dependent protein modulator probably participates in the regulation of contractile response of vascular smooth muscle by affecting actomyosin ATPase activity."}
{"id": "PMID:204384", "title": "[Hormonal factors in the prediction of hormonedependency of breast cancer].", "content": "Biological diagnostic of hormonedependency of breast tumors is important for the choice of treatment. Modifications of the metabolism of steroids, oestrogens, androgens, and glucocorticoids allowed a first approach. More recently, investigations have been made on breast tissue receptors for hormones that are involved in the growth of the normal gland. It is actually suggested that one could predict the hormonedependency of a tumor when it contains both receptors for oestradiol and progesterone.", "contents": "[Hormonal factors in the prediction of hormonedependency of breast cancer]. Biological diagnostic of hormonedependency of breast tumors is important for the choice of treatment. Modifications of the metabolism of steroids, oestrogens, androgens, and glucocorticoids allowed a first approach. More recently, investigations have been made on breast tissue receptors for hormones that are involved in the growth of the normal gland. It is actually suggested that one could predict the hormonedependency of a tumor when it contains both receptors for oestradiol and progesterone."}
{"id": "PMID:204391", "title": "Serum concentrations of 25-hydroxy vitamin D in Europeans and Asians after oral vitamin D3.", "content": "Serum concentrations of 25-hydroxy vitamin D (25-OHD3) were measured in seven Asians of Indian extraction and eight Europeans before and at intervals after taking 1 mg vitamin D3 by mouth. In all subjects the concentrations rose in the 24 hours after ingestion. There was little change over the next nine days in the concentrations in the Europeans but those in the Asians continued to rise until about day 10. Subsequent rates of fall in 25-OHD3 were similar in the two groups. Our observations suggest that the low serum concentrations of 25-OHD3 found in Asians are not caused by either impaired intestinal absorption of vitamin D or rapid clearance of 25-ODH3 from the plasma.", "contents": "Serum concentrations of 25-hydroxy vitamin D in Europeans and Asians after oral vitamin D3. Serum concentrations of 25-hydroxy vitamin D (25-OHD3) were measured in seven Asians of Indian extraction and eight Europeans before and at intervals after taking 1 mg vitamin D3 by mouth. In all subjects the concentrations rose in the 24 hours after ingestion. There was little change over the next nine days in the concentrations in the Europeans but those in the Asians continued to rise until about day 10. Subsequent rates of fall in 25-OHD3 were similar in the two groups. Our observations suggest that the low serum concentrations of 25-OHD3 found in Asians are not caused by either impaired intestinal absorption of vitamin D or rapid clearance of 25-ODH3 from the plasma."}
{"id": "PMID:204392", "title": "Outbreak of Guillain-Barr\u00e9 syndrome associated with water pollution.", "content": "Sixteen cases of Guillain-Barr\u00e9 syndrome occurred in the third week of a diarrhoea epidemic caused by water pollution in EL-Sult, Jordan. Of 30 000 people exposed to polluted water, 5000 developed diarrhoea, 74 typhoid, and 30 infectious hepatitis. Thirteen of the 16 patients with Guillain-Barr\u00e9 syndrome had been mildly affected by diarrhoea 8-24 days before the onset of peripheral neuropathy. Paralysis progressed rapidly, reaching a peak in one to five days, and recovery began three to seven days after the start of the most severe symptoms. All but four patients had recovered completely after one year. Rapid progress of paralysis and a delayed interval between maximum weakness and start of recovery were both associated with poor prognosis.", "contents": "Outbreak of Guillain-Barr\u00e9 syndrome associated with water pollution. Sixteen cases of Guillain-Barr\u00e9 syndrome occurred in the third week of a diarrhoea epidemic caused by water pollution in EL-Sult, Jordan. Of 30 000 people exposed to polluted water, 5000 developed diarrhoea, 74 typhoid, and 30 infectious hepatitis. Thirteen of the 16 patients with Guillain-Barr\u00e9 syndrome had been mildly affected by diarrhoea 8-24 days before the onset of peripheral neuropathy. Paralysis progressed rapidly, reaching a peak in one to five days, and recovery began three to seven days after the start of the most severe symptoms. All but four patients had recovered completely after one year. Rapid progress of paralysis and a delayed interval between maximum weakness and start of recovery were both associated with poor prognosis."}
{"id": "PMID:204400", "title": "Sterol ordering effects and permeability regulation in phosphatidylcholine bilayers. A comparison of ESR spin-probe data from oriented multilamellae and dispersions.", "content": "The effects of a series of sterols on molecular order and motion in bilayers formed from egg lecithin and dicetylphosphate were examined and correlations between order and data on permeability to 22Na+ were sought. Electron spin resonance spectra were observed for probes intercalated both in multilamellar dispersions where the effects of motion and orientation are difficult to separate, and in planar multibilayers where the degree of molecular order may be measured even in the presence of slow probe motion. It was concluded from the planar multi-bilayer data that sterols which increase the degree of ordering of lipid molecules decrease 22Na+ permeability, and that sterols which have the opposite effect on order increase permeability. All the sterols tested lead to decreased rates of motion of the probes. This effect obscures the correlation between order and permeability using data from dispersions.", "contents": "Sterol ordering effects and permeability regulation in phosphatidylcholine bilayers. A comparison of ESR spin-probe data from oriented multilamellae and dispersions. The effects of a series of sterols on molecular order and motion in bilayers formed from egg lecithin and dicetylphosphate were examined and correlations between order and data on permeability to 22Na+ were sought. Electron spin resonance spectra were observed for probes intercalated both in multilamellar dispersions where the effects of motion and orientation are difficult to separate, and in planar multibilayers where the degree of molecular order may be measured even in the presence of slow probe motion. It was concluded from the planar multi-bilayer data that sterols which increase the degree of ordering of lipid molecules decrease 22Na+ permeability, and that sterols which have the opposite effect on order increase permeability. All the sterols tested lead to decreased rates of motion of the probes. This effect obscures the correlation between order and permeability using data from dispersions."}
{"id": "PMID:204401", "title": "The purification and characterization of a DNA nicking-closing enzyme from Bacillus megaterium.", "content": "Although several eucaryote DNA nicking--closing (N--C) enzymes have been characterized, only the Escherichia coli enzyme has been extensively studied amongst procaryotes. The latter enzyme is distinctly different from the eucaryotic enzymes and we have therefore purified the N--C enzyme from Bacillus megaterium to determine if procaryotes form a distinctive class of N--C enzymes. The purified B. megaterium N--C enzyme has a molecular weight of 120,000, only partly relaxes negative supercoils, does not affect positive supercoils, requires Mg2+, and is inhibited by 0.2 M KCl. The enzyme is also inhibited by 1 mM nalidixic or oxolinic acids but unaffected by novobiocin. A crude N--C enzyme preparation from Micrococcus luteus shows very similar properties.", "contents": "The purification and characterization of a DNA nicking-closing enzyme from Bacillus megaterium. Although several eucaryote DNA nicking--closing (N--C) enzymes have been characterized, only the Escherichia coli enzyme has been extensively studied amongst procaryotes. The latter enzyme is distinctly different from the eucaryotic enzymes and we have therefore purified the N--C enzyme from Bacillus megaterium to determine if procaryotes form a distinctive class of N--C enzymes. The purified B. megaterium N--C enzyme has a molecular weight of 120,000, only partly relaxes negative supercoils, does not affect positive supercoils, requires Mg2+, and is inhibited by 0.2 M KCl. The enzyme is also inhibited by 1 mM nalidixic or oxolinic acids but unaffected by novobiocin. A crude N--C enzyme preparation from Micrococcus luteus shows very similar properties."}
{"id": "PMID:204402", "title": "DNA nicking--closing activity from salmon testis.", "content": "Salmon testis is a good source of DNA nicking--closing (N--C) enzyme, as expected for rapidly proliferating cells. Partial purification was obtained but it resulted in an unstable form of N--C enzyme. Cruder fractions are useful for relaxing supercoiled DNA under conditions where other N--C enzymes are inactive. The enzyme is very tolerant of salt concentration, with activity still detectable at 0.6 M NaCl. It is also active at low temperatures with reasonable activity at 0 degrees C. However, at temperatures greater than 25 degrees C it is rapidly inactivated. Otherwise, its properties are similar to other eucaryotic N--C enzymes.", "contents": "DNA nicking--closing activity from salmon testis. Salmon testis is a good source of DNA nicking--closing (N--C) enzyme, as expected for rapidly proliferating cells. Partial purification was obtained but it resulted in an unstable form of N--C enzyme. Cruder fractions are useful for relaxing supercoiled DNA under conditions where other N--C enzymes are inactive. The enzyme is very tolerant of salt concentration, with activity still detectable at 0.6 M NaCl. It is also active at low temperatures with reasonable activity at 0 degrees C. However, at temperatures greater than 25 degrees C it is rapidly inactivated. Otherwise, its properties are similar to other eucaryotic N--C enzymes."}
{"id": "PMID:204398", "title": "Density and protein profiles of myelin from two regions of young and adult rat CNS.", "content": "Myelin, isolated from forebrain and spinal cord of young and adult rats, was distributed by zonal centrifugation on linear (0.32--1.00 M) sucrose gradients in a bell-shaped mode. The peak position of forebrain myelin shifted from the density of 0.58 M sucrose in young animals to that of 0.67 M sucrose in adult rats, while in spinal cord no such pronounced shift was noticed (approximately 0.58 M sucrose). Morphologically, the preparations appeared very similar across the density ranges. Specific activities of acetylcholinesterase were substantially below the total homogenates, while those of 2', 3'-cyclic nucleotide 3'-phosphohydrolase were higher in all fractions, except in the light myelin subfractions from adult spinal cord. Basic proteins decreased from the light to the heavier fractions; higher molecular weight proteins increased, together with proteolipid protein, which in spinal cord reached a plateau and in forebrain decreased towards the heavy side. The ratio of the small basic protein/large basic protein showed higher values in the light myelin subfractions in the regions and ages examined, pointing to a higher degree of maturation.", "contents": "Density and protein profiles of myelin from two regions of young and adult rat CNS. Myelin, isolated from forebrain and spinal cord of young and adult rats, was distributed by zonal centrifugation on linear (0.32--1.00 M) sucrose gradients in a bell-shaped mode. The peak position of forebrain myelin shifted from the density of 0.58 M sucrose in young animals to that of 0.67 M sucrose in adult rats, while in spinal cord no such pronounced shift was noticed (approximately 0.58 M sucrose). Morphologically, the preparations appeared very similar across the density ranges. Specific activities of acetylcholinesterase were substantially below the total homogenates, while those of 2', 3'-cyclic nucleotide 3'-phosphohydrolase were higher in all fractions, except in the light myelin subfractions from adult spinal cord. Basic proteins decreased from the light to the heavier fractions; higher molecular weight proteins increased, together with proteolipid protein, which in spinal cord reached a plateau and in forebrain decreased towards the heavy side. The ratio of the small basic protein/large basic protein showed higher values in the light myelin subfractions in the regions and ages examined, pointing to a higher degree of maturation."}
{"id": "PMID:204403", "title": "A new look at pituitary adenomas: structure elucidating function.", "content": "Cases of seven different types of surgically resected pituitary adenoma are described. Included are tumours secreting prolactin or growth hormone or both, and nonfunctioning tumours--undifferentiated and oncocytic tumours, and one tumour with cells of the adrenocorticotropin-melanocyte-stimulating hormone type. The final interpretation of a case of pituitary adenoma should include an assessment of thorough morphologic studies, using not only routine staining and light microscopy but also immunostaining and electron microscopy, to complement the biochemical, radiologic and clinical evaluation.", "contents": "A new look at pituitary adenomas: structure elucidating function. Cases of seven different types of surgically resected pituitary adenoma are described. Included are tumours secreting prolactin or growth hormone or both, and nonfunctioning tumours--undifferentiated and oncocytic tumours, and one tumour with cells of the adrenocorticotropin-melanocyte-stimulating hormone type. The final interpretation of a case of pituitary adenoma should include an assessment of thorough morphologic studies, using not only routine staining and light microscopy but also immunostaining and electron microscopy, to complement the biochemical, radiologic and clinical evaluation."}
{"id": "PMID:204399", "title": "Effect of a chronic tryptophan dietary deficiency on the rat's sleep-wake cycle.", "content": "The sleep-wake cycle of 12 tryptophan dietary deficient rats and their non-deficient paired controls were observed for a 8:00 a.m. to 8:00 p.m. period. EEG, EMG and body activity were continuously monitored on polygraphic recordings throughout the 12 hr observation period. The results indicate no significant difference between the tryptophan deficient and sufficient animals in time spent awake, slow-wave or parodoxical sleep. There was a non-significant trend among the tryptophan deficient animals to be less active and spend more time in both slow-wave and paradoxical sleep, which is in contrast to an expected insomnia effect. The results do not support the suggested relationship between reduced serotonin levels and the occurrence of insomnia, questioning the serotonergic theory of sleep.", "contents": "Effect of a chronic tryptophan dietary deficiency on the rat's sleep-wake cycle. The sleep-wake cycle of 12 tryptophan dietary deficient rats and their non-deficient paired controls were observed for a 8:00 a.m. to 8:00 p.m. period. EEG, EMG and body activity were continuously monitored on polygraphic recordings throughout the 12 hr observation period. The results indicate no significant difference between the tryptophan deficient and sufficient animals in time spent awake, slow-wave or parodoxical sleep. There was a non-significant trend among the tryptophan deficient animals to be less active and spend more time in both slow-wave and paradoxical sleep, which is in contrast to an expected insomnia effect. The results do not support the suggested relationship between reduced serotonin levels and the occurrence of insomnia, questioning the serotonergic theory of sleep."}
{"id": "PMID:204406", "title": "Contribution of angiography to the diagnosis, staging and assessment of radiation and chemotherapy of solid abdominal malignancies in children.", "content": "Sequential angiographic studies were done in six children to stage and assess the results of radiation and/or chemotherapy of solid abdominal malignancies: one bilateral Wilms' tumor, two neuroblastomas, two hepatoblastomas and one hepatocarcinoma. Angiography was of value in demonstrating the tumor, its location, extent and vascular characteristics, as well as its regression and recurrence. Wilms' tumor and neuroblastoma responded and well to radiation and chemotherapy with substantial decrease in tumor size and regression or disappearance of tumor neovasculature. Resceted tumors revealed this to be due to tumor necrosis, hemorrhage and/or cystic degeneration. Hepatoblastoma and hepatocarcinoma did not respond as well to chemotherapy, with only mild decrease in size and neovasculature of the tumor.", "contents": "Contribution of angiography to the diagnosis, staging and assessment of radiation and chemotherapy of solid abdominal malignancies in children. Sequential angiographic studies were done in six children to stage and assess the results of radiation and/or chemotherapy of solid abdominal malignancies: one bilateral Wilms' tumor, two neuroblastomas, two hepatoblastomas and one hepatocarcinoma. Angiography was of value in demonstrating the tumor, its location, extent and vascular characteristics, as well as its regression and recurrence. Wilms' tumor and neuroblastoma responded and well to radiation and chemotherapy with substantial decrease in tumor size and regression or disappearance of tumor neovasculature. Resceted tumors revealed this to be due to tumor necrosis, hemorrhage and/or cystic degeneration. Hepatoblastoma and hepatocarcinoma did not respond as well to chemotherapy, with only mild decrease in size and neovasculature of the tumor."}
{"id": "PMID:204407", "title": "Radiation therapy in the treatment of malignant salivary gland tumors.", "content": "A retrospective analysis of 52 patients with malignant salivary gland tumors is reported. Seventeen patients received early postoperative radiation therapy and 16 (94%) were free of local or regional disease 2-14 years following initiation of therapy, although 14 were considered at high risk of developing local recurrence. Two subjects (12%) developed distant metastases and 14 (82%) were completely disease-free. Survival and disease-free status of patients treated for recurrent or inoperable disease were much worse with two of 13 disease-free at 45 and 168 months respectively. Various workers have reported recurrence rates after surgery along at 25-38% and over 50% for many histological types. On the basis of this report early postoperative radiation therapy is recommended to reduce the risk of postsurgical recurrence. Prognostic trends relating to both histological type and location of primary disease are discussed.", "contents": "Radiation therapy in the treatment of malignant salivary gland tumors. A retrospective analysis of 52 patients with malignant salivary gland tumors is reported. Seventeen patients received early postoperative radiation therapy and 16 (94%) were free of local or regional disease 2-14 years following initiation of therapy, although 14 were considered at high risk of developing local recurrence. Two subjects (12%) developed distant metastases and 14 (82%) were completely disease-free. Survival and disease-free status of patients treated for recurrent or inoperable disease were much worse with two of 13 disease-free at 45 and 168 months respectively. Various workers have reported recurrence rates after surgery along at 25-38% and over 50% for many histological types. On the basis of this report early postoperative radiation therapy is recommended to reduce the risk of postsurgical recurrence. Prognostic trends relating to both histological type and location of primary disease are discussed."}
{"id": "PMID:204408", "title": "Malignant transformation of esophageal columnar epithelium.", "content": "This report describes two patients with esophageal columnar epithelium (Barrett's esophagus) in which microinvasive adenocarcinoma developed. Case 1 had multiple foci of carcinoma in situ contiguous with epithelium resembling gastric and intestinal mucosa. Case 2 had signet-ring type adenocarcinoma. Surveillance for malignant transformation in columnar esophageal epithelium should be routinely performed, and because of its focal nature, multiple biopsies and cytologic examination should be carried out. The presence of carcinoma in situ should lead to consideration of excision of the affected esophagus.", "contents": "Malignant transformation of esophageal columnar epithelium. This report describes two patients with esophageal columnar epithelium (Barrett's esophagus) in which microinvasive adenocarcinoma developed. Case 1 had multiple foci of carcinoma in situ contiguous with epithelium resembling gastric and intestinal mucosa. Case 2 had signet-ring type adenocarcinoma. Surveillance for malignant transformation in columnar esophageal epithelium should be routinely performed, and because of its focal nature, multiple biopsies and cytologic examination should be carried out. The presence of carcinoma in situ should lead to consideration of excision of the affected esophagus."}
{"id": "PMID:204409", "title": "Malignant fibrous histiocytoma and pleomorphic sarcoma in association with medullary bone infarcts.", "content": "A malignant fibrous histiocytoma arose in the proimal tibia of a 40-year-old man who had multiple, symmetrically distributed, medullary bone infarcts of unknown etiology, involving the distal femora and the tibiae. Despite amputation and chemotherapy, widespread metastases developed and death occurred 19 months after surgery. A polemorphic sarcoma, probably representing an anaplastic malignant fibrous histiocytoma, arose in association with a single medullary infarct in the proximal humerus of a 33-year-old woman. She remains well without evidence of disease five years after treatment by radical radiotherapy followed by shoulder disarticulation. Sarcoma arising in association with bone infarction is a rare entity. Sixteen cases reported in the medical literature, including our own, are reviewed. The sarcomas arose in the tibia in nine cases, the femur in six cases and the humerus in one case. The patients were usually older individuals and 13 of the 16 were male. All but two had multiple bone infarctions. Four of the patients had caisson disease, three had what is probably an hereditary bone dysplasia, one had sickle cell disease and eight had infarcts of unknown etiology. Most patients have had a rapidly fatal outcome. Thirteen of the sarcomas have been fibrosarcomas or malignant fibrous histiocytomas, both of which are rare primary bone tumors. Analysis of the published cases of bone infarction-related sarcomas suggests that the risk of developing a sarcoma is greatest in infarcts with large medullary components.", "contents": "Malignant fibrous histiocytoma and pleomorphic sarcoma in association with medullary bone infarcts. A malignant fibrous histiocytoma arose in the proimal tibia of a 40-year-old man who had multiple, symmetrically distributed, medullary bone infarcts of unknown etiology, involving the distal femora and the tibiae. Despite amputation and chemotherapy, widespread metastases developed and death occurred 19 months after surgery. A polemorphic sarcoma, probably representing an anaplastic malignant fibrous histiocytoma, arose in association with a single medullary infarct in the proximal humerus of a 33-year-old woman. She remains well without evidence of disease five years after treatment by radical radiotherapy followed by shoulder disarticulation. Sarcoma arising in association with bone infarction is a rare entity. Sixteen cases reported in the medical literature, including our own, are reviewed. The sarcomas arose in the tibia in nine cases, the femur in six cases and the humerus in one case. The patients were usually older individuals and 13 of the 16 were male. All but two had multiple bone infarctions. Four of the patients had caisson disease, three had what is probably an hereditary bone dysplasia, one had sickle cell disease and eight had infarcts of unknown etiology. Most patients have had a rapidly fatal outcome. Thirteen of the sarcomas have been fibrosarcomas or malignant fibrous histiocytomas, both of which are rare primary bone tumors. Analysis of the published cases of bone infarction-related sarcomas suggests that the risk of developing a sarcoma is greatest in infarcts with large medullary components."}
{"id": "PMID:204410", "title": "Malignant clear cell acrospiroma.", "content": "The histologic features of a malignant clear cell acrospiroma were those of infiltrative local growth, frequent mitoses and angiolymphatic invasion. The histochemical and ultrastructural findings were similar to those reported for benign clear cell acrospriomas. Amputation of the leg and regional node dissection were required for clinical control. Evaluation of this case and review of the literature suggests that the malignant clear cell acrospiroma often behaves in an aggressive manner and frequently metastasizes. As a consequence, thereapeutic strategies should be appropriately planned.", "contents": "Malignant clear cell acrospiroma. The histologic features of a malignant clear cell acrospiroma were those of infiltrative local growth, frequent mitoses and angiolymphatic invasion. The histochemical and ultrastructural findings were similar to those reported for benign clear cell acrospriomas. Amputation of the leg and regional node dissection were required for clinical control. Evaluation of this case and review of the literature suggests that the malignant clear cell acrospiroma often behaves in an aggressive manner and frequently metastasizes. As a consequence, thereapeutic strategies should be appropriately planned."}
{"id": "PMID:204415", "title": "Immunohistochemical demonstration of alpha-1-antitrypsin in the islet cells of human pancreas.", "content": "Alpha-1-antitrypsin was demonstrated both by immunofluorescence and immunoperoxidase techniques in the peripheral islet cells of 15 normal human pancreases, processed freshly and after embedding in paraffin. Normal human liver obtained from the same patients was negative. The immunohistochemical reactions were stronger in frozen sections than in paraffin material. However, immunoperoxidase staining on paraffin sections permitted a more precise localization of positive cells. The specificity of the immunohistochemical reactions was confirmed by applying various control tests including a absorption of the specific antisera with purified alpha-1-antitrypsin, inhibition and blocking tests. Further examination of pancreatic tissue for the presence of various immunoglobulins, alpha-1-lipoproteins, alpha-1-acid glycoproteins and ceruloplasmin were negative. These findings suggest that the pancreatic islets may be an extra source of alpha-1-antitrypsin.", "contents": "Immunohistochemical demonstration of alpha-1-antitrypsin in the islet cells of human pancreas. Alpha-1-antitrypsin was demonstrated both by immunofluorescence and immunoperoxidase techniques in the peripheral islet cells of 15 normal human pancreases, processed freshly and after embedding in paraffin. Normal human liver obtained from the same patients was negative. The immunohistochemical reactions were stronger in frozen sections than in paraffin material. However, immunoperoxidase staining on paraffin sections permitted a more precise localization of positive cells. The specificity of the immunohistochemical reactions was confirmed by applying various control tests including a absorption of the specific antisera with purified alpha-1-antitrypsin, inhibition and blocking tests. Further examination of pancreatic tissue for the presence of various immunoglobulins, alpha-1-lipoproteins, alpha-1-acid glycoproteins and ceruloplasmin were negative. These findings suggest that the pancreatic islets may be an extra source of alpha-1-antitrypsin."}
{"id": "PMID:204416", "title": "Cytological observations on the blood and hemopoietic tissue in the crab, Callinectes sapidus. I. The fine structure of hemocytes from intermolt animals.", "content": "A fine structural analysis of hemocytes recovered from the pericardial sinus of the blue crab (Callinectes sapidus) demonstrates that hyaline cells, intermediate cells, and granulocytes are present in the hemolymph. A detailed consideration of their shared and differing cytological features suggests that the various blood cells represent different stages of cytogenesis along a common or single path of cellular differentiation. The potential functional complexity of the hemocytes is attested to by the occurrence within their cytoplasm of three and/or possibly four morphologically distinct types of inclusion bodies, and other membrane-bounded compartments (e.g., lysosome-like structures, autophagic vacuoles, peroxisome-like bodies) whose function is unknown. Preliminary examination of the well-developed Golgi organelle in the intermediate cells and granulocytes indicates its probable participation in the elaboration of the inclusion bodies; however, the details of its role in granulogenesis and in the known plurifunctional capacities of these cells remain obscure.", "contents": "Cytological observations on the blood and hemopoietic tissue in the crab, Callinectes sapidus. I. The fine structure of hemocytes from intermolt animals. A fine structural analysis of hemocytes recovered from the pericardial sinus of the blue crab (Callinectes sapidus) demonstrates that hyaline cells, intermediate cells, and granulocytes are present in the hemolymph. A detailed consideration of their shared and differing cytological features suggests that the various blood cells represent different stages of cytogenesis along a common or single path of cellular differentiation. The potential functional complexity of the hemocytes is attested to by the occurrence within their cytoplasm of three and/or possibly four morphologically distinct types of inclusion bodies, and other membrane-bounded compartments (e.g., lysosome-like structures, autophagic vacuoles, peroxisome-like bodies) whose function is unknown. Preliminary examination of the well-developed Golgi organelle in the intermediate cells and granulocytes indicates its probable participation in the elaboration of the inclusion bodies; however, the details of its role in granulogenesis and in the known plurifunctional capacities of these cells remain obscure."}
{"id": "PMID:204418", "title": "Glycogenolysis in amphibian liver organ cultures: effects of isoprenaline, cyclic-AMP, calcium, and the ionophores A23187 and Br-X537A.", "content": "Isoprenaline, db-cAMP and ionophore Br-X537A induced glycogenolysis and glucose release from A. means liver organ cultures in the presence or absence of medium Ca2+. Ionophore A23187 had similar effects, but only in the presence of external Ca2+.", "contents": "Glycogenolysis in amphibian liver organ cultures: effects of isoprenaline, cyclic-AMP, calcium, and the ionophores A23187 and Br-X537A. Isoprenaline, db-cAMP and ionophore Br-X537A induced glycogenolysis and glucose release from A. means liver organ cultures in the presence or absence of medium Ca2+. Ionophore A23187 had similar effects, but only in the presence of external Ca2+."}
{"id": "PMID:204419", "title": "Changes in the content of cyclic AMP and cyclic GMP in eggs of Mactra solidissima during the second cleavage cycle.", "content": "The levels of cyclic AMP and cyclic GMP during the second cleavage cycle of eggs of Mactra solidissima have been measured. Cyclic GMP levels vary reciprocally with cyclic AMP levels, the cyclic GMP level increasing up to 4 to 5-fold and the cyclic AMP level falling to 50 percent at the onset of mitosis.", "contents": "Changes in the content of cyclic AMP and cyclic GMP in eggs of Mactra solidissima during the second cleavage cycle. The levels of cyclic AMP and cyclic GMP during the second cleavage cycle of eggs of Mactra solidissima have been measured. Cyclic GMP levels vary reciprocally with cyclic AMP levels, the cyclic GMP level increasing up to 4 to 5-fold and the cyclic AMP level falling to 50 percent at the onset of mitosis."}
{"id": "PMID:204420", "title": "Phenotypic modification of SV40-transformed hamster lymphoid cells in vivo.", "content": "Explants of simian virus 40 (SV40)-induced lymphoid tumors yield SV40-T-antigen-positive derivatives that differ from GD248 lymphocytes propagated in suspension culture, (or in vivo), in the following respects: polygonal shape, adhesion to culture substrates in vitro, phagocytic capacity, lack of immunoglobulin and a chromosome complement at least twice that of GD248 lymphocytes. When GD-248 lymphocytes are propagated as suspension in vitro, no such adherent variants can be detected. However, sequential in vivo passage of GD248 lymphocytes obtained from the suspension-culture lines also yield adherent cell lines upon explanation in vitro. Injection of adherent cells into hamsters produces tumors with histological features of reticulum cell sarcoma.", "contents": "Phenotypic modification of SV40-transformed hamster lymphoid cells in vivo. Explants of simian virus 40 (SV40)-induced lymphoid tumors yield SV40-T-antigen-positive derivatives that differ from GD248 lymphocytes propagated in suspension culture, (or in vivo), in the following respects: polygonal shape, adhesion to culture substrates in vitro, phagocytic capacity, lack of immunoglobulin and a chromosome complement at least twice that of GD248 lymphocytes. When GD-248 lymphocytes are propagated as suspension in vitro, no such adherent variants can be detected. However, sequential in vivo passage of GD248 lymphocytes obtained from the suspension-culture lines also yield adherent cell lines upon explanation in vitro. Injection of adherent cells into hamsters produces tumors with histological features of reticulum cell sarcoma."}
{"id": "PMID:204421", "title": "Inhibition of internuclear transport of SV40-induced T antigen in heterokaryons.", "content": "Internuclear migration of tumour specific nuclear T antigen has been analysed in SV40-induced H-50 tumour and chick erythrocyte heterokaryons. Thirty hours after cell fusion the incorporated and enlarged erythrocyte nuclei were invariably T antigen-positive. When treated with colchicine at 10(-4) or 10(-7) M concentration, the erythrocyte nuclei incorporated into the heterokaryons did not swell and remained T antigen-negative. The results strongly suggest the involvement of a colchicine sensitive contractile protein matrix in the internuclear transport of T antigen and other proteins.", "contents": "Inhibition of internuclear transport of SV40-induced T antigen in heterokaryons. Internuclear migration of tumour specific nuclear T antigen has been analysed in SV40-induced H-50 tumour and chick erythrocyte heterokaryons. Thirty hours after cell fusion the incorporated and enlarged erythrocyte nuclei were invariably T antigen-positive. When treated with colchicine at 10(-4) or 10(-7) M concentration, the erythrocyte nuclei incorporated into the heterokaryons did not swell and remained T antigen-negative. The results strongly suggest the involvement of a colchicine sensitive contractile protein matrix in the internuclear transport of T antigen and other proteins."}
{"id": "PMID:204422", "title": "Cyclic GMP regulation and responses of Polysphondylium violaceum to chemoattractants.", "content": "In cells of the cellular slime mold Polysphondylium violaceum an attractant, which is released during the aggregation stage, causes a transient rise of the cyclic GMP concentration. Cells of this organism develop in shaken suspensions after they have finished growth. Cell development is not accompanied by an increase in the EDTA stability of cell adhesion. Both the developmental regulation and the specificity of chemotactic responses is reflected in the light scattering patterns recorded in cell suspensions: Folic acid causes a strong response in early preaggregation cells and the Polysphondylium attractant does the same in aggregation competent cells, whereas cyclic AMP is inactive in both stages.", "contents": "Cyclic GMP regulation and responses of Polysphondylium violaceum to chemoattractants. In cells of the cellular slime mold Polysphondylium violaceum an attractant, which is released during the aggregation stage, causes a transient rise of the cyclic GMP concentration. Cells of this organism develop in shaken suspensions after they have finished growth. Cell development is not accompanied by an increase in the EDTA stability of cell adhesion. Both the developmental regulation and the specificity of chemotactic responses is reflected in the light scattering patterns recorded in cell suspensions: Folic acid causes a strong response in early preaggregation cells and the Polysphondylium attractant does the same in aggregation competent cells, whereas cyclic AMP is inactive in both stages."}
{"id": "PMID:204423", "title": "Cyclic-AMP stimulated calcium influx into aggregating cells of Dictyostelium discoideum.", "content": "Within about 10 seconds after stimulation of Dictyostelium discoideum cells with cyclic AMP an increased rate of 45Ca influx was observed. Part of the cellular calcium reappeared in the extra-cellular medium between 1 and 3 minutes after stimulation. No effect of 5'AMP on calcium distribution was found. The transient calcium influx is discussed in connection with chemotaxis and other cyclic-AMP induced responses.", "contents": "Cyclic-AMP stimulated calcium influx into aggregating cells of Dictyostelium discoideum. Within about 10 seconds after stimulation of Dictyostelium discoideum cells with cyclic AMP an increased rate of 45Ca influx was observed. Part of the cellular calcium reappeared in the extra-cellular medium between 1 and 3 minutes after stimulation. No effect of 5'AMP on calcium distribution was found. The transient calcium influx is discussed in connection with chemotaxis and other cyclic-AMP induced responses."}
{"id": "PMID:204428", "title": "Endomyocardial disease and eosinophilia. Report of a case.", "content": "While an association between blood eosinophilia and endomyocardial disease has been recognized, the role of the eosinophil in the pathogenesis of the cardiac lesions remains uncertain. In a 69-year-old-man with large cell carcinoma of the lung, marked eosinophilia was stimulated by and progressed with the course of the neoplasm which was producing an eosinophil chemotactic factor. Peripheral blood eosinophils were vacuolated and degranulated while those in the bone marrow were morphologically normal. Clinical evidence of cardiac dysfunction developed one month prior to death. At autopsy, 12 months after the onset of symptoms, endomyocardial disease was present. There were numerous eosinophils in the damaged myocardium and surrounding the pulmonary neoplasm. In patients with endomyocardial disease and eosinophilia, the eosinophil may be directly cardiotoxic or a primary mediator of cardiac damage; therapeutic attempts to reduce the number of eosinophils might be benefit.", "contents": "Endomyocardial disease and eosinophilia. Report of a case. While an association between blood eosinophilia and endomyocardial disease has been recognized, the role of the eosinophil in the pathogenesis of the cardiac lesions remains uncertain. In a 69-year-old-man with large cell carcinoma of the lung, marked eosinophilia was stimulated by and progressed with the course of the neoplasm which was producing an eosinophil chemotactic factor. Peripheral blood eosinophils were vacuolated and degranulated while those in the bone marrow were morphologically normal. Clinical evidence of cardiac dysfunction developed one month prior to death. At autopsy, 12 months after the onset of symptoms, endomyocardial disease was present. There were numerous eosinophils in the damaged myocardium and surrounding the pulmonary neoplasm. In patients with endomyocardial disease and eosinophilia, the eosinophil may be directly cardiotoxic or a primary mediator of cardiac damage; therapeutic attempts to reduce the number of eosinophils might be benefit."}
{"id": "PMID:204430", "title": "Enzyme immunoassay for human apolipoprotein B, the major protein moiety in low-density- and very-low-density lipoproteins.", "content": "We used enzyme immunoassay to measure apolipoprotein B concentration in human plasma. Pure lipoprotein B was isolated from serum samples of fasting normolipidemic subjects by sequential preparative ultracentrifugation and coated to a polystyrene tube surface by adsorption. Human serum samples and rabbit antiserum to human apolipoprotein B were incubated with the solid-phase lipoprotein B. Soluble antigen competed with solid-phase antigen for binding to antibodies. After washing, peroxidase-labeled sheep antibodies against rabbit immunoglobulins were added, and after further washing the bound label was assayed. This provided a direct measurement of the soluble antigen. The best technical conditions for the assay were determined. The minimum detectable concentration was 1 microgram per assay. The enzyme immunoassay yielded values that compare favorably with those obtained by radial immunodiffusion (r = 0.84) and by rocket immunoelectrophoresis (r = 0.80). The assay offers several advantages over existing techniques: sensitivity, specificity, simplicity, ane non-use of radioisotopes.", "contents": "Enzyme immunoassay for human apolipoprotein B, the major protein moiety in low-density- and very-low-density lipoproteins. We used enzyme immunoassay to measure apolipoprotein B concentration in human plasma. Pure lipoprotein B was isolated from serum samples of fasting normolipidemic subjects by sequential preparative ultracentrifugation and coated to a polystyrene tube surface by adsorption. Human serum samples and rabbit antiserum to human apolipoprotein B were incubated with the solid-phase lipoprotein B. Soluble antigen competed with solid-phase antigen for binding to antibodies. After washing, peroxidase-labeled sheep antibodies against rabbit immunoglobulins were added, and after further washing the bound label was assayed. This provided a direct measurement of the soluble antigen. The best technical conditions for the assay were determined. The minimum detectable concentration was 1 microgram per assay. The enzyme immunoassay yielded values that compare favorably with those obtained by radial immunodiffusion (r = 0.84) and by rocket immunoelectrophoresis (r = 0.80). The assay offers several advantages over existing techniques: sensitivity, specificity, simplicity, ane non-use of radioisotopes."}
{"id": "PMID:204431", "title": "Adenylate kinase inhibition by adenosine 5'-monophosphate and fluoride in the determination of creatine kinase activity.", "content": "The current methods for the determination of creatine kinase (EC 2.7.3.2) activity are derived from Oliver's method, in which AMP is used to decrease interference by adenylate kinase (EC 2.7.4.3). Recently, Szasz et al. and Rosano et al. described methods in which diadenosine pentaphosphate and fluoride, respectively, are used to reduce this interference. However, diadenosine pentaphosphate does not sufficiently inhibit such activity of hepatic origin, while fluoride alone can only inhibit it at concentrations at which the fluoride tends to precipitate as MgF2. Finally, Szasz et al., the Committee on Enzymes of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, and the German Society for Clinical Chemistry have proposed methods in which both AMP and diadenosine pentaphosphate are used to inhibit adenylate kinase. We have found that by using low concentrations of AMP and fluoride together, we can greatly diminish this interference without significant loss of creatine kinase activity and with no precipitation of MgF2.", "contents": "Adenylate kinase inhibition by adenosine 5'-monophosphate and fluoride in the determination of creatine kinase activity. The current methods for the determination of creatine kinase (EC 2.7.3.2) activity are derived from Oliver's method, in which AMP is used to decrease interference by adenylate kinase (EC 2.7.4.3). Recently, Szasz et al. and Rosano et al. described methods in which diadenosine pentaphosphate and fluoride, respectively, are used to reduce this interference. However, diadenosine pentaphosphate does not sufficiently inhibit such activity of hepatic origin, while fluoride alone can only inhibit it at concentrations at which the fluoride tends to precipitate as MgF2. Finally, Szasz et al., the Committee on Enzymes of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, and the German Society for Clinical Chemistry have proposed methods in which both AMP and diadenosine pentaphosphate are used to inhibit adenylate kinase. We have found that by using low concentrations of AMP and fluoride together, we can greatly diminish this interference without significant loss of creatine kinase activity and with no precipitation of MgF2."}
{"id": "PMID:204432", "title": "Nephropathia epidemica: immunohistochemical study of pathogenesis.", "content": "Renal immunohistochemistry was studied in 21 patients with Nephropathia epidemica, a benign hemorrhagic fever endemic in northern Europe. Between days 4 and 25 after the onset of fever, scanty but distinct deposits containing immunoglobulins and C3 were detected in glomeruli and tubules. The occurrence of deposits was verified with electron microscopy. It is concluded that an immune complex mechanism plays a part in the pathogenesis of this disease. It is also evident that the febrile period coincides with the presence of immune complexes in the circulation.", "contents": "Nephropathia epidemica: immunohistochemical study of pathogenesis. Renal immunohistochemistry was studied in 21 patients with Nephropathia epidemica, a benign hemorrhagic fever endemic in northern Europe. Between days 4 and 25 after the onset of fever, scanty but distinct deposits containing immunoglobulins and C3 were detected in glomeruli and tubules. The occurrence of deposits was verified with electron microscopy. It is concluded that an immune complex mechanism plays a part in the pathogenesis of this disease. It is also evident that the febrile period coincides with the presence of immune complexes in the circulation."}
{"id": "PMID:204437", "title": "Gastric calcification detected in vivo by 99mTc-pyrophosphate imaging.", "content": "A 48-year-old white man with Hodgkin's disease was referred for bone imaging. There was intense accumulation of the bone imaging agent in the stomach and in the region of the upper lobe of the right lung. Subsequent biopsy and histological examination revealed that there was amorphous calcifications in the mucosal layer of the stomach. Possible causes for this calcification are discussed.", "contents": "Gastric calcification detected in vivo by 99mTc-pyrophosphate imaging. A 48-year-old white man with Hodgkin's disease was referred for bone imaging. There was intense accumulation of the bone imaging agent in the stomach and in the region of the upper lobe of the right lung. Subsequent biopsy and histological examination revealed that there was amorphous calcifications in the mucosal layer of the stomach. Possible causes for this calcification are discussed."}
{"id": "PMID:204442", "title": "Uptake by bone of pyrophosphate, diphosphonates and their technetium derivatives.", "content": "1. The uptake of inorganic pyrophosphate (PPi) from blood to bone was investigated in the rat in vivo. 2. PPi is taken up by the bone, where it appears both as PPi and as inorganic orthophosphate (Pi). The latter is due at least partly to local hydrolysis. 3. The fraction of injected PPi taken up by bone, measured as total PPi, was in the same range as that of technetium-tin-PPi, diphosphonates, technetium-tin-ethane-1-hydroxy-1,1-diphosphonate and Pi, but lower than that of calcium. 4. The plasma half-life of PPi is in the same order of magnitude as that of technetium-tin-PPi, diphosphonates, technetium-tin-ethane-1-hydroxy-1,1-diphosphonate, Pi and calcium. 5. PPi, diphosphonates and their technetium complexes are only partly ultrafiltrable in plasma. 6. It appears that the technetium complexes behave in a similar fashion to free PPi or diphosphonate.", "contents": "Uptake by bone of pyrophosphate, diphosphonates and their technetium derivatives. 1. The uptake of inorganic pyrophosphate (PPi) from blood to bone was investigated in the rat in vivo. 2. PPi is taken up by the bone, where it appears both as PPi and as inorganic orthophosphate (Pi). The latter is due at least partly to local hydrolysis. 3. The fraction of injected PPi taken up by bone, measured as total PPi, was in the same range as that of technetium-tin-PPi, diphosphonates, technetium-tin-ethane-1-hydroxy-1,1-diphosphonate and Pi, but lower than that of calcium. 4. The plasma half-life of PPi is in the same order of magnitude as that of technetium-tin-PPi, diphosphonates, technetium-tin-ethane-1-hydroxy-1,1-diphosphonate, Pi and calcium. 5. PPi, diphosphonates and their technetium complexes are only partly ultrafiltrable in plasma. 6. It appears that the technetium complexes behave in a similar fashion to free PPi or diphosphonate."}
{"id": "PMID:204443", "title": "The effect of alpha-adrenoreceptor stimulation on the airways of normal and asthmatic man.", "content": "1. The bronchial response to alpha-adrenoreceptor stimulation has been investigated in normal and asthmatic subjects with a specific alpha-receptor agonist, methoxamine hydrochloride, after atropine and beta-adrenergic blockade. 2. No significant changes in forced expiratory volume in 1 s (FEV1.0) were seen in normal subjects. 3. Methoxamine inhalation caused mild symptomatic wheezing and significant falls in FEV1.0 in asthmatic subjects. No change in FEV1.0 occurred after inhalation of distilled water as control. 4. It therefore appears that methoxamine causes bronchoconstriction in asthmatic subjects through its alpha-adrenergic-stimulating properties, since we were not able to detect any beta-receptor-blocking activity of methoxamine on the airways.", "contents": "The effect of alpha-adrenoreceptor stimulation on the airways of normal and asthmatic man. 1. The bronchial response to alpha-adrenoreceptor stimulation has been investigated in normal and asthmatic subjects with a specific alpha-receptor agonist, methoxamine hydrochloride, after atropine and beta-adrenergic blockade. 2. No significant changes in forced expiratory volume in 1 s (FEV1.0) were seen in normal subjects. 3. Methoxamine inhalation caused mild symptomatic wheezing and significant falls in FEV1.0 in asthmatic subjects. No change in FEV1.0 occurred after inhalation of distilled water as control. 4. It therefore appears that methoxamine causes bronchoconstriction in asthmatic subjects through its alpha-adrenergic-stimulating properties, since we were not able to detect any beta-receptor-blocking activity of methoxamine on the airways."}
{"id": "PMID:204446", "title": "Impact of aftercare services on recidivism of mental hospital patients.", "content": "The subjects in this study were 129 patients released within a 2-year period from a large state hospital to a three-county area. Patient information on demographic, inhospital, and posthospital variables and the extent of participation in an aftercare program was collected from existing records. The relationship between the community support system available to the patient and recidivism was determined. Three criteria of recidivism were used: readmission within 1 year following discharge, number of days in the community within 1 year following discharge, and number of days to first readmission. No single predictor was adequate in predicting hospital readmission. When the effects of confounding variables were eliminated using multiple-regression techniques, the amount of aftercare received was an important factor in predicting recidivism. However, current situational factors appeared to be more important predictors of recidivism than receipt of aftercare services.", "contents": "Impact of aftercare services on recidivism of mental hospital patients. The subjects in this study were 129 patients released within a 2-year period from a large state hospital to a three-county area. Patient information on demographic, inhospital, and posthospital variables and the extent of participation in an aftercare program was collected from existing records. The relationship between the community support system available to the patient and recidivism was determined. Three criteria of recidivism were used: readmission within 1 year following discharge, number of days in the community within 1 year following discharge, and number of days to first readmission. No single predictor was adequate in predicting hospital readmission. When the effects of confounding variables were eliminated using multiple-regression techniques, the amount of aftercare received was an important factor in predicting recidivism. However, current situational factors appeared to be more important predictors of recidivism than receipt of aftercare services."}
{"id": "PMID:204447", "title": "Development of an aftercare program in a nonmetropolitan area.", "content": "This article describes the development of a nontraditional aftercare program set in a predominantly rural area. The program was initiated by a citizen's board concerned with the lack of follow-up services provided to patients discharged from a distant state hospital. The planning format as conceived by representatives of this board is outlined and the steps involved in operationalizing specific services and a research program are described. Lastly, a number of limitations of the program and future directions are enumerated.", "contents": "Development of an aftercare program in a nonmetropolitan area. This article describes the development of a nontraditional aftercare program set in a predominantly rural area. The program was initiated by a citizen's board concerned with the lack of follow-up services provided to patients discharged from a distant state hospital. The planning format as conceived by representatives of this board is outlined and the steps involved in operationalizing specific services and a research program are described. Lastly, a number of limitations of the program and future directions are enumerated."}
{"id": "PMID:204448", "title": "Effects of Yunnan Bai Yao on blood platelets: an ultrastructural study.", "content": "The effects of Yunnan Bai Yao on blood platelets were studied at an ultrastructural level. This herbal drug is found to cause the release of platelet constituents which accounts for its hemostatic effects. The fine structural changes of platelets in response to this drug are also described.", "contents": "Effects of Yunnan Bai Yao on blood platelets: an ultrastructural study. The effects of Yunnan Bai Yao on blood platelets were studied at an ultrastructural level. This herbal drug is found to cause the release of platelet constituents which accounts for its hemostatic effects. The fine structural changes of platelets in response to this drug are also described."}
{"id": "PMID:204449", "title": "Diagnosis of equine neurologic problems.", "content": "This is a review of the more common diseases of the spinal cord and various areas of the brain of horses. The results of a two and one-half year study of spinal cord disease are emphasized. After a description of the lesion the salient clinical signs are described and the features that differentiate them from other similar diseases. In the seminar, films of case and slides of lesions will be shown to document these diseases.", "contents": "Diagnosis of equine neurologic problems. This is a review of the more common diseases of the spinal cord and various areas of the brain of horses. The results of a two and one-half year study of spinal cord disease are emphasized. After a description of the lesion the salient clinical signs are described and the features that differentiate them from other similar diseases. In the seminar, films of case and slides of lesions will be shown to document these diseases."}
{"id": "PMID:204450", "title": "Clinicopathological manifestations of selected neoplasms.", "content": "This report provides a general overview of the pathobiology of neoplasia, and an update on the clinicopathological manifestations of lymphosarcoma, mastocytoma, histiocytoma, melanoma, sarcoid and circumanal gland tumors in domestic animals. Neoplasia represents a continuum of events from reversible hyperplasia to irreversible and pathological changes in tissue growth patterns. In some instances the causes of this disease process have been identified, but the etiology of the majority of naturally occurring neoplasms remain unknown. Surgical excision is the preferred treatment for tumors, but is often more beneficial when combined with chemotherapy, radiotherapy or immunotherapy. The successful diagnosis and management of neoplastic disease in domestic animals necessitates a thorough awareness of the clinical presentation and biologic behavior of specific tumors on the part of veterinarians who provide health care for these species.", "contents": "Clinicopathological manifestations of selected neoplasms. This report provides a general overview of the pathobiology of neoplasia, and an update on the clinicopathological manifestations of lymphosarcoma, mastocytoma, histiocytoma, melanoma, sarcoid and circumanal gland tumors in domestic animals. Neoplasia represents a continuum of events from reversible hyperplasia to irreversible and pathological changes in tissue growth patterns. In some instances the causes of this disease process have been identified, but the etiology of the majority of naturally occurring neoplasms remain unknown. Surgical excision is the preferred treatment for tumors, but is often more beneficial when combined with chemotherapy, radiotherapy or immunotherapy. The successful diagnosis and management of neoplastic disease in domestic animals necessitates a thorough awareness of the clinical presentation and biologic behavior of specific tumors on the part of veterinarians who provide health care for these species."}
{"id": "PMID:204452", "title": "The diagnostic laboratory and its relationship to practitioners. Diagnostic laboratory professional staff.", "content": "Diagnostic services provided to practitioners include necropsy, histopathology, bacteriology, virology, parasitology, immunopathology, clinical pathology and toxicology. Services are also available at the college in avian and aquatic diseases. The laboratory expects to continually upgrade its services through the addition of appropriate tests, re-evaluation of existing tests, development of methods for more convenient specimen collection and shipment, increased responsiveness to veterinarians' needs, epidemiological investigations, and continuing education.", "contents": "The diagnostic laboratory and its relationship to practitioners. Diagnostic laboratory professional staff. Diagnostic services provided to practitioners include necropsy, histopathology, bacteriology, virology, parasitology, immunopathology, clinical pathology and toxicology. Services are also available at the college in avian and aquatic diseases. The laboratory expects to continually upgrade its services through the addition of appropriate tests, re-evaluation of existing tests, development of methods for more convenient specimen collection and shipment, increased responsiveness to veterinarians' needs, epidemiological investigations, and continuing education."}
{"id": "PMID:204455", "title": "The canine contagious respiratory disease complex (kennel cough).", "content": "Several infectious agents are involved in the kennel cough complex in dogs. They include canine parainfluenza virus (SV5), canine adenovirus 2, Bordetella bronchiseptica, and possibly several mycoplasma species. The importance of each of these agents in the disease syndrome is discussed as well as possible prevention or treatment.", "contents": "The canine contagious respiratory disease complex (kennel cough). Several infectious agents are involved in the kennel cough complex in dogs. They include canine parainfluenza virus (SV5), canine adenovirus 2, Bordetella bronchiseptica, and possibly several mycoplasma species. The importance of each of these agents in the disease syndrome is discussed as well as possible prevention or treatment."}
{"id": "PMID:204458", "title": "Pituitary--adrenal responsiveness of rat mothers to noxious stimuli and stimuli produced by pups.", "content": "Studies on the response of female rats to various stresses during the course of lactation showed a marked reduction in pituitary-adrenal activity. Maximum suppression coincided with the period of maximum lactation, about 14 days after parturition. Both pituitary corticotropin and the release of corticosterone were significantly reduced. Females showing maternal behaviour but not lactating did not exhibit this buffering of the stress response. Another aspect of pituitary-adrenal activity has been studied in lactating female rats. Females, although they have a buffered stress response, responded differently, in terms of pituitary-adrenal activity, to stimuli emitted by the pups: pups which are exposed to noxious stimuli elicit a much greater pituitary-adrenal response in lactating females than do pups which are merely handled. Separation from the pups does not elicit a pituitary-adrenal response. This difference in response is modified if the infants are malnourished and is not observed in virgin animals that are not lactating.", "contents": "Pituitary--adrenal responsiveness of rat mothers to noxious stimuli and stimuli produced by pups. Studies on the response of female rats to various stresses during the course of lactation showed a marked reduction in pituitary-adrenal activity. Maximum suppression coincided with the period of maximum lactation, about 14 days after parturition. Both pituitary corticotropin and the release of corticosterone were significantly reduced. Females showing maternal behaviour but not lactating did not exhibit this buffering of the stress response. Another aspect of pituitary-adrenal activity has been studied in lactating female rats. Females, although they have a buffered stress response, responded differently, in terms of pituitary-adrenal activity, to stimuli emitted by the pups: pups which are exposed to noxious stimuli elicit a much greater pituitary-adrenal response in lactating females than do pups which are merely handled. Separation from the pups does not elicit a pituitary-adrenal response. This difference in response is modified if the infants are malnourished and is not observed in virgin animals that are not lactating."}
{"id": "PMID:204459", "title": "Purine biosynthesis in mutant mammalian cells.", "content": "De novo purine biosynthesis has been studied in lymphocyte cell lines established from Lesch-Nyhan patients deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT), in in vitro differentiating erythroleukaemic cell lines cloned from cells charactistic of virus-induced murine leukaemia, and in mutant hamster cells deficient in amidophosphoribosyltransferase. The relationship between cellular phosphoribosylpyrophosphate (PP-ribose-P) metabolism and the activity of the enzymes which catalyse the early steps of de novo purine biosynthesis has been explored. It was found that hamster cells deficient in amidophosphoribosyltransferase did not accumulate PP-ribose-P as do HGPRT-deficient cells. In these model systems, an accelerated rate of de novo purine biosynthesis tended to be associated with an increase in cellular PP-ribose-P cotent, but decreases in this rate results from the reduction in the activity of amidophosphoribosyltransferase. Regulation of ammonia-dependent de novo purine biosynthesis was similar to that of glutamine-dependent purine biosynthesis.", "contents": "Purine biosynthesis in mutant mammalian cells. De novo purine biosynthesis has been studied in lymphocyte cell lines established from Lesch-Nyhan patients deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT), in in vitro differentiating erythroleukaemic cell lines cloned from cells charactistic of virus-induced murine leukaemia, and in mutant hamster cells deficient in amidophosphoribosyltransferase. The relationship between cellular phosphoribosylpyrophosphate (PP-ribose-P) metabolism and the activity of the enzymes which catalyse the early steps of de novo purine biosynthesis has been explored. It was found that hamster cells deficient in amidophosphoribosyltransferase did not accumulate PP-ribose-P as do HGPRT-deficient cells. In these model systems, an accelerated rate of de novo purine biosynthesis tended to be associated with an increase in cellular PP-ribose-P cotent, but decreases in this rate results from the reduction in the activity of amidophosphoribosyltransferase. Regulation of ammonia-dependent de novo purine biosynthesis was similar to that of glutamine-dependent purine biosynthesis."}
{"id": "PMID:204460", "title": "Superactivity of phosphoribosylpyrophosphate synthetase, due to feedback resistance, causing purine overproduction and gout.", "content": "A mutant feedback-resistant, physiologically superactive, phosphoribosylpyrophosphate (PP-ribose-P) synthetase was found in a family with purine overproduction, gout and uric acid lithiasis. In haemolysates and cultured fibroblasts from the propositus, the mutant enzyme exhibited resistance to feedback inhibition by normal cell constituents, such as ADP and GDP; normal affinity to substrates and to activator Pi was demonstrated in the haemolysate. In both erythrocytes and cultured fibroblasts, the superactivity of the mutant enzyme was manifest in increased PP-ribose-P content and availability for nucleotide synthesis, leading to an acceleration of the rate of purine synthesis de novo in the fibroblasts. The enzyme abnormality and the resulting increase in PP-ribose-P content and generation were demonstrated in the erythrocytes of one of the propositus' two siblings who was similarly affected but not in the propositus' father, his second brother and four sons, who were all clinically and biochemically normal, nor in the erythrocytes of the clinically normal hyperuricosuric mother. However, cultured fibroblasts from her skin exhibited variability in PP-ribose-P content and availability and in the rate of purine synthesis de novo, these parameters being increased in most cultures. The mother's fibroblast cultures were found to contain two cell populations, one with normal and the other with mutant PP-ribose-P synthetase, indicating an X-linked pattern of inheritance of the synthetase superactivity in this gouty family.", "contents": "Superactivity of phosphoribosylpyrophosphate synthetase, due to feedback resistance, causing purine overproduction and gout. A mutant feedback-resistant, physiologically superactive, phosphoribosylpyrophosphate (PP-ribose-P) synthetase was found in a family with purine overproduction, gout and uric acid lithiasis. In haemolysates and cultured fibroblasts from the propositus, the mutant enzyme exhibited resistance to feedback inhibition by normal cell constituents, such as ADP and GDP; normal affinity to substrates and to activator Pi was demonstrated in the haemolysate. In both erythrocytes and cultured fibroblasts, the superactivity of the mutant enzyme was manifest in increased PP-ribose-P content and availability for nucleotide synthesis, leading to an acceleration of the rate of purine synthesis de novo in the fibroblasts. The enzyme abnormality and the resulting increase in PP-ribose-P content and generation were demonstrated in the erythrocytes of one of the propositus' two siblings who was similarly affected but not in the propositus' father, his second brother and four sons, who were all clinically and biochemically normal, nor in the erythrocytes of the clinically normal hyperuricosuric mother. However, cultured fibroblasts from her skin exhibited variability in PP-ribose-P content and availability and in the rate of purine synthesis de novo, these parameters being increased in most cultures. The mother's fibroblast cultures were found to contain two cell populations, one with normal and the other with mutant PP-ribose-P synthetase, indicating an X-linked pattern of inheritance of the synthetase superactivity in this gouty family."}
{"id": "PMID:204461", "title": "Purine metabolism and control of cell proliferation.", "content": "Exposure of normal lymphocytes to phytohaemagglutinin or other lectin mitogens results in increased concentrations of 5-phosphoribosyl-1-pyrophosphate (PP-ribose-P) within minutes. Subsequently, synthesis of purine nucleotides by both the de novo and the salvage pathways is facilitated. This change is prevented by proliferation-inhibiting concentrations of exogenous adenosine. The capacity of lymphocytes to metabolize both adenine and adenosine is increased several-fold by incubation with phytohaemagglutinin but the specific activities of the respective first-step enzymes are not significantly altered. These results suggest that the relatively low quantity of PP-ribose-P available in normal lymphocytes is a major factor limiting the synthesis of purine nucleotides and may be important for the maintenance of the quiescent state. Increased availability of PP-ribose-P may also be associated with proliferative activation of fibroblast-like cells: chick embryo fibroblast cultures released from density-dependent inhibition of growth by insulin, trypsin or serum rapidly increase the rate of adenine incorporation into nucleotides. Chick embryo fibroblasts transformed by Rous sarcoma virus, but not cells infected with the respective non-transforming leukosis virus, show PP-ribose-P concentrations higher than those observed in normal cells.", "contents": "Purine metabolism and control of cell proliferation. Exposure of normal lymphocytes to phytohaemagglutinin or other lectin mitogens results in increased concentrations of 5-phosphoribosyl-1-pyrophosphate (PP-ribose-P) within minutes. Subsequently, synthesis of purine nucleotides by both the de novo and the salvage pathways is facilitated. This change is prevented by proliferation-inhibiting concentrations of exogenous adenosine. The capacity of lymphocytes to metabolize both adenine and adenosine is increased several-fold by incubation with phytohaemagglutinin but the specific activities of the respective first-step enzymes are not significantly altered. These results suggest that the relatively low quantity of PP-ribose-P available in normal lymphocytes is a major factor limiting the synthesis of purine nucleotides and may be important for the maintenance of the quiescent state. Increased availability of PP-ribose-P may also be associated with proliferative activation of fibroblast-like cells: chick embryo fibroblast cultures released from density-dependent inhibition of growth by insulin, trypsin or serum rapidly increase the rate of adenine incorporation into nucleotides. Chick embryo fibroblasts transformed by Rous sarcoma virus, but not cells infected with the respective non-transforming leukosis virus, show PP-ribose-P concentrations higher than those observed in normal cells."}
{"id": "PMID:204462", "title": "Microbial models and regulatory elements in the control of purine metabolism.", "content": "Bacterial systems have been used to identify and characterize the organization of the genetic units and the regulatory elements that control purine metabolism. An analysis of 13 genes that control the biosynthesis of AMP and GMP has revealed three multigenic operons. These show properties of gene contiguity, promoter sites, coordinate expression and polarity effects. The unit controlling the formation of IMP is one operon (pur JHD) consisting of three genes which together control the formation of phosphoribosylglycinamide synthetase (EC 6.3.4.13), an early enzyme in the biosynthetic pathway, and a terminal bifunctional complex (IMP cyclohydrolase--formyltransferase). Regulatory mutants were isolated and characterized by several methods including the use of a unique fusion of two unrelated operons. Both operator constitutive and repressor type (purR) mutations have been identified. The purR product functions in the common control of several genetically distinct enzymes that participate before the formation of IMP. Plasmid DNA enriched for the purE operon has been isolated and used in the study of the role of nucleotide effectors in the binding of repressor-like proteins. AMP but not GMP is needed for binding, and purR mutants are deficient in the binding substance. Mutants with differential blocks in the salvage and interconverting reactions have been used to characterize the regulatory elements of the formation and the activity of guanosine kinase, GMP reductase (EC 1.6.6.8), and purine nucleoside phosphorylase (EC 2.4.2.1). Two structural gene products (purF) and (purG) have been implicated as possible regulatory elements for the use of guanosine, and a role for glutamine in the induction of GMP reductase has been revealed.", "contents": "Microbial models and regulatory elements in the control of purine metabolism. Bacterial systems have been used to identify and characterize the organization of the genetic units and the regulatory elements that control purine metabolism. An analysis of 13 genes that control the biosynthesis of AMP and GMP has revealed three multigenic operons. These show properties of gene contiguity, promoter sites, coordinate expression and polarity effects. The unit controlling the formation of IMP is one operon (pur JHD) consisting of three genes which together control the formation of phosphoribosylglycinamide synthetase (EC 6.3.4.13), an early enzyme in the biosynthetic pathway, and a terminal bifunctional complex (IMP cyclohydrolase--formyltransferase). Regulatory mutants were isolated and characterized by several methods including the use of a unique fusion of two unrelated operons. Both operator constitutive and repressor type (purR) mutations have been identified. The purR product functions in the common control of several genetically distinct enzymes that participate before the formation of IMP. Plasmid DNA enriched for the purE operon has been isolated and used in the study of the role of nucleotide effectors in the binding of repressor-like proteins. AMP but not GMP is needed for binding, and purR mutants are deficient in the binding substance. Mutants with differential blocks in the salvage and interconverting reactions have been used to characterize the regulatory elements of the formation and the activity of guanosine kinase, GMP reductase (EC 1.6.6.8), and purine nucleoside phosphorylase (EC 2.4.2.1). Two structural gene products (purF) and (purG) have been implicated as possible regulatory elements for the use of guanosine, and a role for glutamine in the induction of GMP reductase has been revealed."}
{"id": "PMID:204463", "title": "The effect of adenosine on lymphoid cell proliferation and antibody formation.", "content": "The discovery of an association of certain primary defects in human purine metabolism with immunodeficiency disease has served to focus attention on the possible role of purine compounds in the functional activity of lymphoic cells. Considerable evidence has accumulated of the need within the intact organism for purine and pyrimidine compounds supplied by the liver as a supplementary nutritional requirement for the growth of the rapidly proliferating tissues of certain organ systems. Likewise, lymphoid cells cultured in vitro show evidence of an enhancement of indices of cellular proliferation and of antibody synthesis when exogenous adenosine is added to the medium. These functions are inhibited by high concentrations of adenosine and there is some evidence that T-cell proliferation shows a greater sensitivity to inhibition by adenosine than B-cells. These observations may be significant in relation to the known defects in human purine metabolism and their mechanism for producing immunodeficiency.", "contents": "The effect of adenosine on lymphoid cell proliferation and antibody formation. The discovery of an association of certain primary defects in human purine metabolism with immunodeficiency disease has served to focus attention on the possible role of purine compounds in the functional activity of lymphoic cells. Considerable evidence has accumulated of the need within the intact organism for purine and pyrimidine compounds supplied by the liver as a supplementary nutritional requirement for the growth of the rapidly proliferating tissues of certain organ systems. Likewise, lymphoid cells cultured in vitro show evidence of an enhancement of indices of cellular proliferation and of antibody synthesis when exogenous adenosine is added to the medium. These functions are inhibited by high concentrations of adenosine and there is some evidence that T-cell proliferation shows a greater sensitivity to inhibition by adenosine than B-cells. These observations may be significant in relation to the known defects in human purine metabolism and their mechanism for producing immunodeficiency."}
{"id": "PMID:204464", "title": "Purine and pyrimidine metabolism: pathways, pitfalls and perturbations.", "content": "The conceptual framework which underlies many studies of purine and pyrimidine metabolism in intact cells has been critically evaluated. The model that is implicit in many such studies is the single, partially purified enzyme. This paper gives examples both of instances in which the extrapolation of results of enzymes studies to intact cells has been successful and of instances in which enzymes behave differently in the intact cell than in cell extracts. Pitfalls in the extrapolation of results of enzyme studies to intact cells concern (a) metabolic pathways, (b) intracellular enzyme activities, (c) enzyme regulation, and (d) intracellular metabolite concentrations. Examples are also given of situations in which perturbations in one aspect of purine or pyrimidine metabolism lead to changes in other aspects, often distant in the network of reactions.", "contents": "Purine and pyrimidine metabolism: pathways, pitfalls and perturbations. The conceptual framework which underlies many studies of purine and pyrimidine metabolism in intact cells has been critically evaluated. The model that is implicit in many such studies is the single, partially purified enzyme. This paper gives examples both of instances in which the extrapolation of results of enzymes studies to intact cells has been successful and of instances in which enzymes behave differently in the intact cell than in cell extracts. Pitfalls in the extrapolation of results of enzyme studies to intact cells concern (a) metabolic pathways, (b) intracellular enzyme activities, (c) enzyme regulation, and (d) intracellular metabolite concentrations. Examples are also given of situations in which perturbations in one aspect of purine or pyrimidine metabolism lead to changes in other aspects, often distant in the network of reactions."}
{"id": "PMID:204472", "title": "Effect of bilateral superior cervical ganglionectomy (SCG) on pituitary adrenal function in the male albino rat.", "content": "The effect of sympathetic denervation (bilateral superior cervical ganglionectomy) on several aspects of pituitary adrenal function was studied in 250-300g rats. Group I=Sham-op, Group II=superior cervical ganglionectomy. (1) There was no significant difference between these groups in the plasma corticosterone (B) response to ether or immobilization stress or to ACTH administration. (2) Circadian periodicity of plasma B was determined by sequential (q.4h) tail vein sampling under LD (lights on 0800) off 2000) and under DL (lights on 2000, off 0800). Both groups showed similar peak and trough concentrations. Phase shifting occurred in both groups at day 11. (3) Compensatory adrenal hypertrophy of similar magnitude was present in both groups 10 days following unilateral adrenalectomy. These studies indicate that sympathetic input from the superior cervical ganglia is not involved in stress induced, circadian or some feedback aspects of pituitary adrenal function.", "contents": "Effect of bilateral superior cervical ganglionectomy (SCG) on pituitary adrenal function in the male albino rat. The effect of sympathetic denervation (bilateral superior cervical ganglionectomy) on several aspects of pituitary adrenal function was studied in 250-300g rats. Group I=Sham-op, Group II=superior cervical ganglionectomy. (1) There was no significant difference between these groups in the plasma corticosterone (B) response to ether or immobilization stress or to ACTH administration. (2) Circadian periodicity of plasma B was determined by sequential (q.4h) tail vein sampling under LD (lights on 0800) off 2000) and under DL (lights on 2000, off 0800). Both groups showed similar peak and trough concentrations. Phase shifting occurred in both groups at day 11. (3) Compensatory adrenal hypertrophy of similar magnitude was present in both groups 10 days following unilateral adrenalectomy. These studies indicate that sympathetic input from the superior cervical ganglia is not involved in stress induced, circadian or some feedback aspects of pituitary adrenal function."}
{"id": "PMID:204473", "title": "Prolactin receptors in mammary tumors of GR mice.", "content": "Prolactin receptors have been identified in estrone-progesterone induced mammary tumors from GR mice. 125I-labeled ovine prolactin binding to tumor homogenates reached a steady state in 12 hours at 22 degrees and was specific for prolactin. Prolactin receptors were highest (16 fmoles/mg protein) in primary, hormone-dependent tumors and declined progressively in transplanted hormone-dependent and transplanted hormone-responsive tumors. In autonomous tumors, binding was approximately 5% of that found in primary tumors. Scatchard analysis of binding to selected tumors indicated that the observed decrease in bound hormone was due to a loss in the number of receptor sites; binding affinity was unaltered (kd approximately 1 X 10(-10) M). Since receptors for estrogen and progesterone as well as those for prolactin decline in a concerted manner with the transition to autonomy, autonomous growth may result from a loss of receptors or an increase in the relative proportion of autonomous cells present in the tumor.", "contents": "Prolactin receptors in mammary tumors of GR mice. Prolactin receptors have been identified in estrone-progesterone induced mammary tumors from GR mice. 125I-labeled ovine prolactin binding to tumor homogenates reached a steady state in 12 hours at 22 degrees and was specific for prolactin. Prolactin receptors were highest (16 fmoles/mg protein) in primary, hormone-dependent tumors and declined progressively in transplanted hormone-dependent and transplanted hormone-responsive tumors. In autonomous tumors, binding was approximately 5% of that found in primary tumors. Scatchard analysis of binding to selected tumors indicated that the observed decrease in bound hormone was due to a loss in the number of receptor sites; binding affinity was unaltered (kd approximately 1 X 10(-10) M). Since receptors for estrogen and progesterone as well as those for prolactin decline in a concerted manner with the transition to autonomy, autonomous growth may result from a loss of receptors or an increase in the relative proportion of autonomous cells present in the tumor."}
{"id": "PMID:204475", "title": "Postnatal development of gonadotropin binding sites and cAMP synthesis in ovaries and estradiol plasma levels in estrogenized or androgenized female rats.", "content": "The binding of 125I-HCG by ovarian homogenates was studied in adolescent rats injected with 100 microgram estradiol dipropionate or 50 microgram testosterone propionate at the age of three days. Estrogenized and androgenized female rats showed a decrease of gonadotropin binding in ovaries at the 25th postnatal day. After the day 40, however, there was an increase in gonadotropin binding capacity above that in control animals. The changes of specific binding of 125I-HCG by ovaries of rats neonatally treated with sex hormones did not correlate with either the responsiveness of cAMP synthesis in ovaries to LH or with plasma levels of estradiol-17beta in postnatal development.", "contents": "Postnatal development of gonadotropin binding sites and cAMP synthesis in ovaries and estradiol plasma levels in estrogenized or androgenized female rats. The binding of 125I-HCG by ovarian homogenates was studied in adolescent rats injected with 100 microgram estradiol dipropionate or 50 microgram testosterone propionate at the age of three days. Estrogenized and androgenized female rats showed a decrease of gonadotropin binding in ovaries at the 25th postnatal day. After the day 40, however, there was an increase in gonadotropin binding capacity above that in control animals. The changes of specific binding of 125I-HCG by ovaries of rats neonatally treated with sex hormones did not correlate with either the responsiveness of cAMP synthesis in ovaries to LH or with plasma levels of estradiol-17beta in postnatal development."}
{"id": "PMID:204476", "title": "The long search for the causes of congenital malformations in mammals.", "content": "The history of teratology is reviewed. Methods available for causing malformations in mammals by subtle changes in the environment during pregnancy are discussed. A table is provided in which the commoner teratogens are listed. Methods are described by means of which the activity of some common teratogens may be opposed. The occurrence at Battle Creek, Michigan, USA, of a chemical agent dangerous to health, life and development of all mammals is described. This gives an indication that injury and death to all mammals, as in the Sevaso disaster, including teratogenesis may be expected to be a fairly frequent occurrence in the years to come.", "contents": "The long search for the causes of congenital malformations in mammals. The history of teratology is reviewed. Methods available for causing malformations in mammals by subtle changes in the environment during pregnancy are discussed. A table is provided in which the commoner teratogens are listed. Methods are described by means of which the activity of some common teratogens may be opposed. The occurrence at Battle Creek, Michigan, USA, of a chemical agent dangerous to health, life and development of all mammals is described. This gives an indication that injury and death to all mammals, as in the Sevaso disaster, including teratogenesis may be expected to be a fairly frequent occurrence in the years to come."}
{"id": "PMID:204477", "title": "Translation of ascites and mengovirus RNA in fractionated cell-free systems from uninfected and mengovirus-infected Ehrlich-ascites-tumor cells.", "content": "We have prepared homologous, fractionated, cell-free translational systems from uninfected and mengovirus-infected Ehrlich ascites tumor cells in order to determine what alterations occur following virus infection in the translational machinery of the host cell. Two major differences distinguish the system developed from infected cells. First, it has a 40% lower rate of protein synthesis, primarily a consequence of the rate of chain elongation, which is depressed to 60 amino acids/min from 90 amino acids/min in the system from uninfected cells. Second, at supraoptimal concentrations of Mg2+ and K+ the system from virus-infected cells supports the translation of mengovirus RNA but not host mRNA. These differences between the two systems may reflect specific changes which are responsible for the selective translation of mengovirus RNA in the infected cell. In both systems the optimal concentrations of polyamines, monovalent and divalent cations, mRNA, and ribosomal subunits are the same for the translation of either host or viral RNA. This uniformity is useful in experiments, designed to investigate the selective translation of viral RNA, where various components of the two systems are interchanged.", "contents": "Translation of ascites and mengovirus RNA in fractionated cell-free systems from uninfected and mengovirus-infected Ehrlich-ascites-tumor cells. We have prepared homologous, fractionated, cell-free translational systems from uninfected and mengovirus-infected Ehrlich ascites tumor cells in order to determine what alterations occur following virus infection in the translational machinery of the host cell. Two major differences distinguish the system developed from infected cells. First, it has a 40% lower rate of protein synthesis, primarily a consequence of the rate of chain elongation, which is depressed to 60 amino acids/min from 90 amino acids/min in the system from uninfected cells. Second, at supraoptimal concentrations of Mg2+ and K+ the system from virus-infected cells supports the translation of mengovirus RNA but not host mRNA. These differences between the two systems may reflect specific changes which are responsible for the selective translation of mengovirus RNA in the infected cell. In both systems the optimal concentrations of polyamines, monovalent and divalent cations, mRNA, and ribosomal subunits are the same for the translation of either host or viral RNA. This uniformity is useful in experiments, designed to investigate the selective translation of viral RNA, where various components of the two systems are interchanged."}
{"id": "PMID:204478", "title": "Selective translation of mengovirus RNA over Host mRNA in homologous, fractionated, cell-free translational systems from Ehrlich-ascites-tumor cells.", "content": "The selective translation of viral RNA in mengovirus-infected Ehrlich ascites tumor cells was investigated using fractionated translational systems whose macromolecular components were derived entirely from uninfected or virus-infected cells. Both systems translate host mRNA from uninfected cells, host mRNA from virus-infected cells, and mengovirus RNA. In competition experiments, where viral RNA and host mRNA were translated together in systems from uninfected cells, the relative amounts of virus-specific and host-specific proteins synthesized were proportional to the relative concentrations of the RNA templates. In systems whose components were obtained from virus-infected cells, mengovirus RNA was preferentially translated. 70% of the selectivity found in the translational systems derived from infected cells was due to the initiation factor fraction, the remaining 30% to components of the pH 5 enzyme fraction. In addition, host mRNA isolated after virus infection is translated in vitro to a lower extent in the presence of mengovirus RNA than is host mRNA from uninfected cells.", "contents": "Selective translation of mengovirus RNA over Host mRNA in homologous, fractionated, cell-free translational systems from Ehrlich-ascites-tumor cells. The selective translation of viral RNA in mengovirus-infected Ehrlich ascites tumor cells was investigated using fractionated translational systems whose macromolecular components were derived entirely from uninfected or virus-infected cells. Both systems translate host mRNA from uninfected cells, host mRNA from virus-infected cells, and mengovirus RNA. In competition experiments, where viral RNA and host mRNA were translated together in systems from uninfected cells, the relative amounts of virus-specific and host-specific proteins synthesized were proportional to the relative concentrations of the RNA templates. In systems whose components were obtained from virus-infected cells, mengovirus RNA was preferentially translated. 70% of the selectivity found in the translational systems derived from infected cells was due to the initiation factor fraction, the remaining 30% to components of the pH 5 enzyme fraction. In addition, host mRNA isolated after virus infection is translated in vitro to a lower extent in the presence of mengovirus RNA than is host mRNA from uninfected cells."}
{"id": "PMID:204479", "title": "Mechanism of activation of protein kinase I from rabbit skeletal muscle. Mapping of the cAMP site by spin-labeled cyclic nucleotides.", "content": "Binding of adenosine 3':5'-monophosphate (cAMP) to protein kinase (type I) from rabbit skeletal muscle has been investigated using spin-labeled cAMP derivatives. Different compounds were synthesized with the spin label attached by spacer chains of different length at different positions on the adenine base. Immobilization of the spin label, determined by comparing the electron-spin resonance spectra recorded in the presence of the kinase with those of the free ligand in solutions of different viscosities, gave information about the geometry of the cAMP site. Strong immobilization of the N-6 substituents up to a spacer length of seven atoms indicates a rather deep cleft of the cAMP site. The depth of this cleft differs, however, when the spin label is attached to the different positions at the adenine (N-6, C-2 and C-8). Whereas the N-6 derivatives indicate a rather deep site, the C-2 derivatives reveal a significantly smaller depth and C-8 substituents (syn conformation) obviously occupy a very shallow surface with almost no immobilation. In addition the binding affinities of the spin-labeled cAMP derivatives have been determined, together with those of a series of (diamagnetic) C-2 derivatives bearing hydrophobic alkyl chains of different length. The latter results helped to clarify the differences between the regions near to C-2 and N-6, respectively, of the cAMP site. N-6 spin-labeled derivatives have also been investigated in the presence of ATP and protein kinase. These results are interpreted as indicative of a conformational change at the cAMP site upon formation of the holoenzyme, due to binding of ATP, leaving cAMP less strongly immobilized.", "contents": "Mechanism of activation of protein kinase I from rabbit skeletal muscle. Mapping of the cAMP site by spin-labeled cyclic nucleotides. Binding of adenosine 3':5'-monophosphate (cAMP) to protein kinase (type I) from rabbit skeletal muscle has been investigated using spin-labeled cAMP derivatives. Different compounds were synthesized with the spin label attached by spacer chains of different length at different positions on the adenine base. Immobilization of the spin label, determined by comparing the electron-spin resonance spectra recorded in the presence of the kinase with those of the free ligand in solutions of different viscosities, gave information about the geometry of the cAMP site. Strong immobilization of the N-6 substituents up to a spacer length of seven atoms indicates a rather deep cleft of the cAMP site. The depth of this cleft differs, however, when the spin label is attached to the different positions at the adenine (N-6, C-2 and C-8). Whereas the N-6 derivatives indicate a rather deep site, the C-2 derivatives reveal a significantly smaller depth and C-8 substituents (syn conformation) obviously occupy a very shallow surface with almost no immobilation. In addition the binding affinities of the spin-labeled cAMP derivatives have been determined, together with those of a series of (diamagnetic) C-2 derivatives bearing hydrophobic alkyl chains of different length. The latter results helped to clarify the differences between the regions near to C-2 and N-6, respectively, of the cAMP site. N-6 spin-labeled derivatives have also been investigated in the presence of ATP and protein kinase. These results are interpreted as indicative of a conformational change at the cAMP site upon formation of the holoenzyme, due to binding of ATP, leaving cAMP less strongly immobilized."}
{"id": "PMID:204481", "title": "Pyrophosphate-stimulated uptake of calcium into the germlings of Phytophthora infestans.", "content": "The uptake of 1 micrometer calcium into 6-h-old germination tubes of the fungus Phytophthora infestans follows Michaelis-Menten kinetics with a Km of 33 +/- 4 micrometer and a V of 0.3 nmol.min-1.(5 x 10(4) cells)-1. Uptake is inhibited by ruthenium red and lanthanum (both at 1 micrometer) and by the proton conductors 2,4-dinitrophenol (1 mM) and carbonylcyanide m-chlorophenylhydrazone and carbonylcyanide p-trifluoromethoxyphenylhydrazone (1--10 micrometer) and also by sodium azide. These data suggest that calcium uptake is dependent on energy and on a carrier. Calcium uptake is stimulated by pyrophosphate but not by ATP, orthophosphate, or polyphosphate. This stimulation is prevented by proton conductors or by incubation at 0 degrees C.", "contents": "Pyrophosphate-stimulated uptake of calcium into the germlings of Phytophthora infestans. The uptake of 1 micrometer calcium into 6-h-old germination tubes of the fungus Phytophthora infestans follows Michaelis-Menten kinetics with a Km of 33 +/- 4 micrometer and a V of 0.3 nmol.min-1.(5 x 10(4) cells)-1. Uptake is inhibited by ruthenium red and lanthanum (both at 1 micrometer) and by the proton conductors 2,4-dinitrophenol (1 mM) and carbonylcyanide m-chlorophenylhydrazone and carbonylcyanide p-trifluoromethoxyphenylhydrazone (1--10 micrometer) and also by sodium azide. These data suggest that calcium uptake is dependent on energy and on a carrier. Calcium uptake is stimulated by pyrophosphate but not by ATP, orthophosphate, or polyphosphate. This stimulation is prevented by proton conductors or by incubation at 0 degrees C."}
{"id": "PMID:204482", "title": "Circular dichroic properties and conformation of thionicotinamide dinucleotides.", "content": "The spectroscopic properties of the 3-thioamide analogues of coenzymes NAD and NADH (sNAD and sNADH) have been investigated in order to obtain information about their conformational properties. In particular, ultraviolet absorption and circular dichroism properties of solutions in phosphate buffer pH 7 and ethanol were studied. Also equimolar mixtures of AMP and sNMN(H), obtained by cleaving the coenzymes with phosphodiesterase, were investigated using the same solvents. The appearance of a couplet around 260 nm, which is not present for the mixture of sNMN and AMP, suggests a stacking interaction of the two aromatic moieties in sNAD. This conclusion is further substantiated by a hyperchroism of the ultraviolet absorption band in the 260-nm region in both sNAD and sNADH. The comparison of the ultraviolet and circular dichroic properties of intact and cleaved coenzymes in the different solvent systems makes it possible to single out the bands which are more sensitive to conformation changes (i.e. to open-stacking equilibrium) and those which are sensitive to solvent effects only.", "contents": "Circular dichroic properties and conformation of thionicotinamide dinucleotides. The spectroscopic properties of the 3-thioamide analogues of coenzymes NAD and NADH (sNAD and sNADH) have been investigated in order to obtain information about their conformational properties. In particular, ultraviolet absorption and circular dichroism properties of solutions in phosphate buffer pH 7 and ethanol were studied. Also equimolar mixtures of AMP and sNMN(H), obtained by cleaving the coenzymes with phosphodiesterase, were investigated using the same solvents. The appearance of a couplet around 260 nm, which is not present for the mixture of sNMN and AMP, suggests a stacking interaction of the two aromatic moieties in sNAD. This conclusion is further substantiated by a hyperchroism of the ultraviolet absorption band in the 260-nm region in both sNAD and sNADH. The comparison of the ultraviolet and circular dichroic properties of intact and cleaved coenzymes in the different solvent systems makes it possible to single out the bands which are more sensitive to conformation changes (i.e. to open-stacking equilibrium) and those which are sensitive to solvent effects only."}
{"id": "PMID:204483", "title": "Circular dichroic properties and conformation of thionicotinamide dinucleotides bound to horse-liver alcohol dehydrogenase.", "content": "The interaction between horse liver alcohol dehydrogenase and the oxidized and reduced forms of the 3-thionicotinamide--adenine dinucleotide coenzyme analogues (sNAD and sNADH) has been investigated by ultraviolet absorption, fluorescence and circular dichroism. The fluorescence of sNADH is enhanced when bound to the enzyme, and the protein fluorescence is quenched by both sNADH (60--65%) and sNAD (65%). The possible origin of the larger quenching produced by sNAD with respect to that of NAD is discussed. Coenzyme dissociation constants have been determined by monitoring the quenching of the protein fluorescence, and some kinetic consequences of these dissociation constants are discussed. The dichroic properties of various enzyme complexes have been investigated, and are discussed in terms of conformational changes and environmental changes during coenzyme binding. The conformation of sNAD bound to the enzyme in the presence of trifluorethanol and the conformation of sNADH bound to the enzyme in the presence of isobutyramide have been analyzed in particular detail. Also the circular dichroic spectrum of the apoenzyme is discussed in terms of contributions of the aromatic amino acid residues in the highly resolved 240--310-nm region and in terms of helix content in the 220-nm region.", "contents": "Circular dichroic properties and conformation of thionicotinamide dinucleotides bound to horse-liver alcohol dehydrogenase. The interaction between horse liver alcohol dehydrogenase and the oxidized and reduced forms of the 3-thionicotinamide--adenine dinucleotide coenzyme analogues (sNAD and sNADH) has been investigated by ultraviolet absorption, fluorescence and circular dichroism. The fluorescence of sNADH is enhanced when bound to the enzyme, and the protein fluorescence is quenched by both sNADH (60--65%) and sNAD (65%). The possible origin of the larger quenching produced by sNAD with respect to that of NAD is discussed. Coenzyme dissociation constants have been determined by monitoring the quenching of the protein fluorescence, and some kinetic consequences of these dissociation constants are discussed. The dichroic properties of various enzyme complexes have been investigated, and are discussed in terms of conformational changes and environmental changes during coenzyme binding. The conformation of sNAD bound to the enzyme in the presence of trifluorethanol and the conformation of sNADH bound to the enzyme in the presence of isobutyramide have been analyzed in particular detail. Also the circular dichroic spectrum of the apoenzyme is discussed in terms of contributions of the aromatic amino acid residues in the highly resolved 240--310-nm region and in terms of helix content in the 220-nm region."}
{"id": "PMID:204484", "title": "Fluorescence properties of reduced thionicotinamide--adenine dinucleotide and of its complex with octopine dehydrogenase.", "content": "Reduced 3-thionicotinamide--adenine dinucleotide (sNADH) is shown to be fluorescent, with an emission maximum at 510 nm when excited in the region of the absorption maximum (398 nm), and with a very low quantum yield, (3.4 +/- 0.5) x 10(-4). The interaction between sNADH and octopine dehydrogenase was investigated by ultraviolet-difference spectroscopy and fluorescence. Some surprising fluorescence features were found when sNADH was bound to the enzyme in the presence of D-octopine, as follows. (a) There is an unusually high enhancement of the dinucleotide fluorescence (by at least a factor of 100) attended by a 40-nm blue shift of the emission maximum. (b) The protein fluorescence is quenched almost completely. (c) The bound coenzyme analog undergoes a photoreaction, which proceeds differently from that occurring the free form. These features appear to be unique to the octopine.sNADH complex, as for example they are not present when sNADH is bound to horse liver alcohol dehydrogenase, or when NADH is bound to octopine dehydrogenase. The possible origin of these fluorescence features is discussed. Binding and kinetic studies were carried out with sNAD and sNADH. It was found that sNAD neither binds nor acts kinetically as a coenzyme. sNADH exhibits relatively good binding, with Km and Ki values close to those of the natural coenzyme, but the turnover number is 460 times smaller than that with NADH. The kinetic consequences of these findings are discussed. The sNADH dissociation constants were determined as a function of temperature, and appear to be practically temperature-independent in the range 10--40 degrees C. It seems thus, in agreement with previous studies, that the interaction between octopine dehydrogenase and coenzymes proceeds athermically, regardless of the structure, affinity, and chemical reactivity of the coenzyme. The possible biological and chemical meaning of this finding is discussed.", "contents": "Fluorescence properties of reduced thionicotinamide--adenine dinucleotide and of its complex with octopine dehydrogenase. Reduced 3-thionicotinamide--adenine dinucleotide (sNADH) is shown to be fluorescent, with an emission maximum at 510 nm when excited in the region of the absorption maximum (398 nm), and with a very low quantum yield, (3.4 +/- 0.5) x 10(-4). The interaction between sNADH and octopine dehydrogenase was investigated by ultraviolet-difference spectroscopy and fluorescence. Some surprising fluorescence features were found when sNADH was bound to the enzyme in the presence of D-octopine, as follows. (a) There is an unusually high enhancement of the dinucleotide fluorescence (by at least a factor of 100) attended by a 40-nm blue shift of the emission maximum. (b) The protein fluorescence is quenched almost completely. (c) The bound coenzyme analog undergoes a photoreaction, which proceeds differently from that occurring the free form. These features appear to be unique to the octopine.sNADH complex, as for example they are not present when sNADH is bound to horse liver alcohol dehydrogenase, or when NADH is bound to octopine dehydrogenase. The possible origin of these fluorescence features is discussed. Binding and kinetic studies were carried out with sNAD and sNADH. It was found that sNAD neither binds nor acts kinetically as a coenzyme. sNADH exhibits relatively good binding, with Km and Ki values close to those of the natural coenzyme, but the turnover number is 460 times smaller than that with NADH. The kinetic consequences of these findings are discussed. The sNADH dissociation constants were determined as a function of temperature, and appear to be practically temperature-independent in the range 10--40 degrees C. It seems thus, in agreement with previous studies, that the interaction between octopine dehydrogenase and coenzymes proceeds athermically, regardless of the structure, affinity, and chemical reactivity of the coenzyme. The possible biological and chemical meaning of this finding is discussed."}
{"id": "PMID:204485", "title": "Fatty acid beta-oxidation system in microbodies of n-alkane-grown Candida tropicalis.", "content": "Localization of fatty acid beta-oxidation system in microbodies of Candida tropicalis cells growing on n-alkanes was studied. Microbodies isolated from the yeast cells showed palmitate-dependent activities of NAD reduction, acetyl-CoA formation and oxygen consumption. When sodium azide, an inhibitor of catalase, was added to the system, palmitate-dependent formation of hydrogen peroxide was observed. Stoichiometric study revealed that two moles of NAD were reduced per one mole of oxygen consumed in the absence of sodium azide and the presence of the inhibitor doubled the oxygen consumption by microbodies without an appreciable change in NAD reduction. These results indicate that the yeast microbodies contain beta-oxidation system of fatty acid, and that catalase located in the organelles participates in the degradation of hydrogen peroxide to be formed at the step of dehydrogenation of acyl-CoA.", "contents": "Fatty acid beta-oxidation system in microbodies of n-alkane-grown Candida tropicalis. Localization of fatty acid beta-oxidation system in microbodies of Candida tropicalis cells growing on n-alkanes was studied. Microbodies isolated from the yeast cells showed palmitate-dependent activities of NAD reduction, acetyl-CoA formation and oxygen consumption. When sodium azide, an inhibitor of catalase, was added to the system, palmitate-dependent formation of hydrogen peroxide was observed. Stoichiometric study revealed that two moles of NAD were reduced per one mole of oxygen consumed in the absence of sodium azide and the presence of the inhibitor doubled the oxygen consumption by microbodies without an appreciable change in NAD reduction. These results indicate that the yeast microbodies contain beta-oxidation system of fatty acid, and that catalase located in the organelles participates in the degradation of hydrogen peroxide to be formed at the step of dehydrogenation of acyl-CoA."}
{"id": "PMID:204486", "title": "Comparison of viable and nonviable tumor uptake of Sc-46, Mn-54, Zn-65, In-111 and Au-195 with Ga-67 citrate in a hepatoma model.", "content": "The tissue distribution of Sc-46, Mn-54, Zn-65, In-111 and Au-195 were studied in a rat hepatoma model at various time intervals over a 96 h period. The tumor localizing properties of these isotopes were evaluated by examining their incorporation and clearance from viable and nonviable tumor tissue and determining the critical tissue ratios formed with blood and muscle. In general, the results showed greater uptake in viable than nonviable tumor tissue at early time periods (4-24 h). By 96 h, however, the activity remaining in the nonviable tumor tissue exceeded the quantity in viable tumor tissue. This trend was previously noted for Ga-67. When compared with Ga-67, only Mn-54 among the isotopes studied showed remarkably higher viable tumor/blood ratios (4-24 h, 45:1-83:1 respectively). Manganese-54 also showed highly significant accumulation in cardiac muscle with a heart/blood ratio at 4 h superior to comparable values previously reported for Cs-137 and Tl-201. It is suggested that tumor and heart imaging may be feasible utilizing radioactive manganese (Mn-51 or Mn-52) with the new positron imaging systems.", "contents": "Comparison of viable and nonviable tumor uptake of Sc-46, Mn-54, Zn-65, In-111 and Au-195 with Ga-67 citrate in a hepatoma model. The tissue distribution of Sc-46, Mn-54, Zn-65, In-111 and Au-195 were studied in a rat hepatoma model at various time intervals over a 96 h period. The tumor localizing properties of these isotopes were evaluated by examining their incorporation and clearance from viable and nonviable tumor tissue and determining the critical tissue ratios formed with blood and muscle. In general, the results showed greater uptake in viable than nonviable tumor tissue at early time periods (4-24 h). By 96 h, however, the activity remaining in the nonviable tumor tissue exceeded the quantity in viable tumor tissue. This trend was previously noted for Ga-67. When compared with Ga-67, only Mn-54 among the isotopes studied showed remarkably higher viable tumor/blood ratios (4-24 h, 45:1-83:1 respectively). Manganese-54 also showed highly significant accumulation in cardiac muscle with a heart/blood ratio at 4 h superior to comparable values previously reported for Cs-137 and Tl-201. It is suggested that tumor and heart imaging may be feasible utilizing radioactive manganese (Mn-51 or Mn-52) with the new positron imaging systems."}
{"id": "PMID:204487", "title": "Triple radioisotope technique in etiologic evaluation of space-occupying lesions of the liver.", "content": "The findings from 43 patients with histologically proven focal liver disease examined by triple isotope tracer study are presented. The method consisted in a three step technique, the first step being an isotope scan after injection of 99mTc-sulfur colloid and 131I rose bengal. As a second step dynamic hepatic scintiangiography was carried out with 99mTc human serum albumin in order to assess the vascularity of a lesion detected on the initial scan. Thirdly, the patient was administered 67Ga to evaluate further the pathologic process. According to our results this triple radioisotope technique provides the clinician with valuable information on the possible etiology of focal liver disease.", "contents": "Triple radioisotope technique in etiologic evaluation of space-occupying lesions of the liver. The findings from 43 patients with histologically proven focal liver disease examined by triple isotope tracer study are presented. The method consisted in a three step technique, the first step being an isotope scan after injection of 99mTc-sulfur colloid and 131I rose bengal. As a second step dynamic hepatic scintiangiography was carried out with 99mTc human serum albumin in order to assess the vascularity of a lesion detected on the initial scan. Thirdly, the patient was administered 67Ga to evaluate further the pathologic process. According to our results this triple radioisotope technique provides the clinician with valuable information on the possible etiology of focal liver disease."}
{"id": "PMID:204488", "title": "Cyclic AMP in cereborspinal fluid of rats: effects of electroconvulsive shock.", "content": "The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) was measured in cisternal cerebrospinal fluid (CSF) of male and female rats after electroconvulsive shock. cAMP levels were found to be increased compared to sham-treated controls for several hours following electroconvulsive shock with maximal increases of 46.8% in male and 17.2% in female rats. Old rats (300--360 g body weight) showed higher baseline concentrations than younger rats (180--250 g). In both groups female rats tended to have higher cAMP levels than male rats.", "contents": "Cyclic AMP in cereborspinal fluid of rats: effects of electroconvulsive shock. The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) was measured in cisternal cerebrospinal fluid (CSF) of male and female rats after electroconvulsive shock. cAMP levels were found to be increased compared to sham-treated controls for several hours following electroconvulsive shock with maximal increases of 46.8% in male and 17.2% in female rats. Old rats (300--360 g body weight) showed higher baseline concentrations than younger rats (180--250 g). In both groups female rats tended to have higher cAMP levels than male rats."}
{"id": "PMID:204491", "title": "Cholestyramine and ileal by-pass in the treatment of familial hypercholesterolaemia.", "content": "A comparison was made of the therapeutic effectiveness of cholestyramine and an ileal by-pass operation as hypocholesterolaemic measures in thirteen patients with familial xanthomatotic type II hypercholesterolaemia. Serum cholesterol and faecal steroids were measured before and at the end of a 10 day course of cholestyramine (32 g/day), and subsequently after an ileal by-pass operation. The mean decrease in serum cholesterol caused by cholestyramine (-17%) was significantly less than that caused by the surgical procedure (-33%). The increase in faecal steroid excretion, mainly as bile acids, was lower with cholestyramine (1.261 g/day) than after the ileal exclusion (2.176 g/day) and a positive correlation was found between the decrease in serum cholesterol and the increase in the faecal elimination of steroids of cholesterol origin. However, even though the increase in faecal steroids with cholestyramine was positively correlated with that resulting from ileal by-pass, the correlation between the corresponding changes in serum cholesterol level was not significant. The findings indicate that ileal by-pass decreases serum cholesterol and increases faecal elimination of cholesterol more effectively than cholestyramine, and that the decrease in the serum cholesterol level induced by ileal exclusion is not consistently predictable by the serum cholesterol response to the preceding cholestyramine treatment.", "contents": "Cholestyramine and ileal by-pass in the treatment of familial hypercholesterolaemia. A comparison was made of the therapeutic effectiveness of cholestyramine and an ileal by-pass operation as hypocholesterolaemic measures in thirteen patients with familial xanthomatotic type II hypercholesterolaemia. Serum cholesterol and faecal steroids were measured before and at the end of a 10 day course of cholestyramine (32 g/day), and subsequently after an ileal by-pass operation. The mean decrease in serum cholesterol caused by cholestyramine (-17%) was significantly less than that caused by the surgical procedure (-33%). The increase in faecal steroid excretion, mainly as bile acids, was lower with cholestyramine (1.261 g/day) than after the ileal exclusion (2.176 g/day) and a positive correlation was found between the decrease in serum cholesterol and the increase in the faecal elimination of steroids of cholesterol origin. However, even though the increase in faecal steroids with cholestyramine was positively correlated with that resulting from ileal by-pass, the correlation between the corresponding changes in serum cholesterol level was not significant. The findings indicate that ileal by-pass decreases serum cholesterol and increases faecal elimination of cholesterol more effectively than cholestyramine, and that the decrease in the serum cholesterol level induced by ileal exclusion is not consistently predictable by the serum cholesterol response to the preceding cholestyramine treatment."}
{"id": "PMID:204493", "title": "Serum immunoreactive prolyl hydroxylase in liver disease.", "content": "The concentration of serum immunoreactive prolyl hydroxylase (SIRPH) was measured in thirty patients with chronic active hepatitis, thirteen with primary biliary cirrhosis, four with alcoholic or idiopathic cirrhosis, and four with acute hepatitis; the values were compared with those in twenty-three control subjects. Increases in SIRPH were found in all the groups with liver diseases, individual values being highest in primary biliary cirrhosis in which about two-thirds of patients had values more than two standard deviations above the mean value in the control subjects. No correlation was found between SIRPH and other tests of liver function or some routine laboratory tests. SIRPH may reflect some hitherto unknown of unmeasured process in the diseased hepatic cells.", "contents": "Serum immunoreactive prolyl hydroxylase in liver disease. The concentration of serum immunoreactive prolyl hydroxylase (SIRPH) was measured in thirty patients with chronic active hepatitis, thirteen with primary biliary cirrhosis, four with alcoholic or idiopathic cirrhosis, and four with acute hepatitis; the values were compared with those in twenty-three control subjects. Increases in SIRPH were found in all the groups with liver diseases, individual values being highest in primary biliary cirrhosis in which about two-thirds of patients had values more than two standard deviations above the mean value in the control subjects. No correlation was found between SIRPH and other tests of liver function or some routine laboratory tests. SIRPH may reflect some hitherto unknown of unmeasured process in the diseased hepatic cells."}
{"id": "PMID:204494", "title": "Arterial and coronary sinus catecholamines and cyclic-AMP during dynamic supine exercise in patients with chest pain.", "content": "Arterial and coronary sinus catecholamine concentrations were measured during dynamic exercise in patients to assess the sympathetic response. Arterial concentrations increased from 1.77 nmol/1 (SEM = 0.53, n = 7) (control) to 2.95 nmol/1 (SEM = 0.65, n = 7) during exercise (0.05 greater than P greater than 0.01) and coronary sinus concentrations from 2.78 nmol/1 (SEM = 0.53, n = 7) (control) to 4.43 nmol/1 (SEM = 0.71, n = 7) (0.05 greater than P greater than 0.01). Resting, and exercise, arterial-coronary sinus differences in catecholamine concentrations were not statistically significant. In some patients, higher catecholamine concentrations occurred post-exercise than during exercise. The coronary sinus-arterial difference in catecholamine concentration during exercise was greatest in the one patient who developed angina pectoris. Cyclic-AMP concentrations were also measured, but these did not change significantly, consistent with the predominantly noradrenaline response to exercise.", "contents": "Arterial and coronary sinus catecholamines and cyclic-AMP during dynamic supine exercise in patients with chest pain. Arterial and coronary sinus catecholamine concentrations were measured during dynamic exercise in patients to assess the sympathetic response. Arterial concentrations increased from 1.77 nmol/1 (SEM = 0.53, n = 7) (control) to 2.95 nmol/1 (SEM = 0.65, n = 7) during exercise (0.05 greater than P greater than 0.01) and coronary sinus concentrations from 2.78 nmol/1 (SEM = 0.53, n = 7) (control) to 4.43 nmol/1 (SEM = 0.71, n = 7) (0.05 greater than P greater than 0.01). Resting, and exercise, arterial-coronary sinus differences in catecholamine concentrations were not statistically significant. In some patients, higher catecholamine concentrations occurred post-exercise than during exercise. The coronary sinus-arterial difference in catecholamine concentration during exercise was greatest in the one patient who developed angina pectoris. Cyclic-AMP concentrations were also measured, but these did not change significantly, consistent with the predominantly noradrenaline response to exercise."}
{"id": "PMID:204496", "title": "Effect of a human serum thymic factor on hydrocortisone-treated thymocytes.", "content": "A human serum thymic factors (SF) stimulated cyclic adenosine-3' ,5'-monophosphate (cAMP) synthesis in normal mouse thymocytes. Such stimulation was no longer observed when thymocytes were depleted of hydrocortisone (HC)-sensitive cells. It was concluded that SF selectively stimulate cAMP in HC-sensitive cells. Furthermore, incubation of thymocytes with SF enlarged the population of HC-resistant thymocytes. These results suggest that SF might act on HC-sensitive thymocytes increasing their cellular cAMP level and inducing their transformation in HC-resistant cells.", "contents": "Effect of a human serum thymic factor on hydrocortisone-treated thymocytes. A human serum thymic factors (SF) stimulated cyclic adenosine-3' ,5'-monophosphate (cAMP) synthesis in normal mouse thymocytes. Such stimulation was no longer observed when thymocytes were depleted of hydrocortisone (HC)-sensitive cells. It was concluded that SF selectively stimulate cAMP in HC-sensitive cells. Furthermore, incubation of thymocytes with SF enlarged the population of HC-resistant thymocytes. These results suggest that SF might act on HC-sensitive thymocytes increasing their cellular cAMP level and inducing their transformation in HC-resistant cells."}
{"id": "PMID:204498", "title": "The opiate receptor binding interactions of 3H-methionine enkephalin, an opioid peptide.", "content": "3H-Methionine enkephalin binds stereospecifically with high affinity to opiate receptors in rat brain membranes. Equilibrium experiments indicate two distinct dissociation constants with KD values of 1.8 and 5.8 nM respectively. 3H-Methionine enkephalin associates and dissociates from the opiate receptor with 8--10 fold slower kinetics than 3H-opiates. Though several opiates have similar affinities for sites labeled by 3H-methionine enkephalin, 3H-dihydromorphine and 3H-naloxone, some opiates such as morphine, dihydromorphine and oxymorphone are only one tenth as potent in competing for 3H-methionine enkephalin as for 3H-dihydromorphine and 3H-naloxone binding. As with other opiate agonists, 5--10 mM sodium selectively decreases the binding of 3H-methionine enkephalin. At 26 degrees C, 0.1--1.0 mM manganese but not magnesium or calcium increases the binding of 3H-methionine enkephalin, while at 0 degrees C manganese decreases the binding of methionine enkephalin.", "contents": "The opiate receptor binding interactions of 3H-methionine enkephalin, an opioid peptide. 3H-Methionine enkephalin binds stereospecifically with high affinity to opiate receptors in rat brain membranes. Equilibrium experiments indicate two distinct dissociation constants with KD values of 1.8 and 5.8 nM respectively. 3H-Methionine enkephalin associates and dissociates from the opiate receptor with 8--10 fold slower kinetics than 3H-opiates. Though several opiates have similar affinities for sites labeled by 3H-methionine enkephalin, 3H-dihydromorphine and 3H-naloxone, some opiates such as morphine, dihydromorphine and oxymorphone are only one tenth as potent in competing for 3H-methionine enkephalin as for 3H-dihydromorphine and 3H-naloxone binding. As with other opiate agonists, 5--10 mM sodium selectively decreases the binding of 3H-methionine enkephalin. At 26 degrees C, 0.1--1.0 mM manganese but not magnesium or calcium increases the binding of 3H-methionine enkephalin, while at 0 degrees C manganese decreases the binding of methionine enkephalin."}
{"id": "PMID:204499", "title": "Behavioural despair in rats: a new model sensitive to antidepressant treatments.", "content": "Rats when forced to swim in a cylinder from which they cannot escape will, after an initial period of vigorous activity, adopt a  characteristic immobile posture which can be readily identified. Immobility was reduced by various clinically effective antidepressant drugs at doses which otherwise decreased spontaneous motor activity in an open field. Antidepressants could thus be distinguished from psychostimulants which decreased immobility at doses which increased general activity. Anxiolytic compounds did not affect immobility whereas major tranquilisers enhanced it. Immobility was also reduced by electroconvulsive shock, REM sleep deprivation and \"enrichment\" of the environment. It was concluded that immobility reflects a state of lowered mood in the rat which is selectively sensitive to antidepressant treatments. Positive findings with atypical antidepressant drugs such as iprindole and mianserin suggest that the method may be capable of discovering new antidepressants hitherto undetectable with classical pharmacological tests.", "contents": "Behavioural despair in rats: a new model sensitive to antidepressant treatments. Rats when forced to swim in a cylinder from which they cannot escape will, after an initial period of vigorous activity, adopt a  characteristic immobile posture which can be readily identified. Immobility was reduced by various clinically effective antidepressant drugs at doses which otherwise decreased spontaneous motor activity in an open field. Antidepressants could thus be distinguished from psychostimulants which decreased immobility at doses which increased general activity. Anxiolytic compounds did not affect immobility whereas major tranquilisers enhanced it. Immobility was also reduced by electroconvulsive shock, REM sleep deprivation and \"enrichment\" of the environment. It was concluded that immobility reflects a state of lowered mood in the rat which is selectively sensitive to antidepressant treatments. Positive findings with atypical antidepressant drugs such as iprindole and mianserin suggest that the method may be capable of discovering new antidepressants hitherto undetectable with classical pharmacological tests."}
{"id": "PMID:204500", "title": "Neurochemical and behavioral effects of clonidine and related imidazolines: interaction with alpha-adrenoceptors.", "content": "Clonidine and other imidazolines, including phentolamine, inhibited the norepinephrine-elicited accumulation of cyclic AMP in brain slices via blockade or postsynpatic alpha-adrenoceptors. Clonidine (0.0125--0.050 mg/kg, i.p.) antagonized the increase in locomotor activity induced by amphetamine in a dose-dependent manner. It is suggested that the common ability of clonidine and phentolamine to antagonize norepinephrine-stimulated accumulation of cyclic AMP provides a possible explanation for the similar behavioral effects of these compounds, including their antagonism of the locomotor effects of amphetamine.", "contents": "Neurochemical and behavioral effects of clonidine and related imidazolines: interaction with alpha-adrenoceptors. Clonidine and other imidazolines, including phentolamine, inhibited the norepinephrine-elicited accumulation of cyclic AMP in brain slices via blockade or postsynpatic alpha-adrenoceptors. Clonidine (0.0125--0.050 mg/kg, i.p.) antagonized the increase in locomotor activity induced by amphetamine in a dose-dependent manner. It is suggested that the common ability of clonidine and phentolamine to antagonize norepinephrine-stimulated accumulation of cyclic AMP provides a possible explanation for the similar behavioral effects of these compounds, including their antagonism of the locomotor effects of amphetamine."}
{"id": "PMID:204507", "title": "An assessment of the effect of hormone and neurotransmitters on adenine and guanine derivatives simultaneously in rat brain cortical slices.", "content": "A A 2-dimensional thin-layer method has been developed for the separation on cellulose of adenine and guanine derivatives. Using incubated rat cerebral cortex slices it was shown that noradrenaline and acetylcholine stimulated cAMP and cGMP production respectively but glutamate and gamma-aminobutyric acid stimulated production of both cyclic nucleotides.", "contents": "An assessment of the effect of hormone and neurotransmitters on adenine and guanine derivatives simultaneously in rat brain cortical slices. A A 2-dimensional thin-layer method has been developed for the separation on cellulose of adenine and guanine derivatives. Using incubated rat cerebral cortex slices it was shown that noradrenaline and acetylcholine stimulated cAMP and cGMP production respectively but glutamate and gamma-aminobutyric acid stimulated production of both cyclic nucleotides."}
{"id": "PMID:204508", "title": "Neutrophils are mediators of antiviral immunity.", "content": "The paper presents evidence that polymorphonuclear neutrophils upon stimulation with herpesvirus-induced antigens release a material inhibitory to virus infection. The material does not appear to be identical to type I or II interferon.", "contents": "Neutrophils are mediators of antiviral immunity. The paper presents evidence that polymorphonuclear neutrophils upon stimulation with herpesvirus-induced antigens release a material inhibitory to virus infection. The material does not appear to be identical to type I or II interferon."}
{"id": "PMID:204509", "title": "Effect of carbenoxolone on phosphodiesterase and prostaglandin synthetase activities.", "content": "Carbenoxolone inhibited in vitro cAMP and cGMP phosphodiesterases in a concentration-dependent and noncompetitive manner. Prostaglandin synthetase activity of rabbit kidney medulla was slightly stimulated by carbenoxolone 0.1--0.5 mM, but inhibited by higher concentrations.", "contents": "Effect of carbenoxolone on phosphodiesterase and prostaglandin synthetase activities. Carbenoxolone inhibited in vitro cAMP and cGMP phosphodiesterases in a concentration-dependent and noncompetitive manner. Prostaglandin synthetase activity of rabbit kidney medulla was slightly stimulated by carbenoxolone 0.1--0.5 mM, but inhibited by higher concentrations."}
{"id": "PMID:204511", "title": "Ergoline derivatives with oral, prolonged, alpha-adrenolytic activity.", "content": "The alpha-adrenolytic activity of 1-methyl-10-methoxydihydrolysergol 2-(3,5-dimethyl)pyrrolcarboxylate (XV, formula II) is, both in vitro and parenterally, quite similar to that of dihydroergotamine. By oral route the new compound is more active, and longer lasting than dihydroergotamine.", "contents": "Ergoline derivatives with oral, prolonged, alpha-adrenolytic activity. The alpha-adrenolytic activity of 1-methyl-10-methoxydihydrolysergol 2-(3,5-dimethyl)pyrrolcarboxylate (XV, formula II) is, both in vitro and parenterally, quite similar to that of dihydroergotamine. By oral route the new compound is more active, and longer lasting than dihydroergotamine."}
{"id": "PMID:204512", "title": "[Research on substances with antiviral activity. VIII. Benzindanoncarboxylic acids].", "content": "New derivatives (esters, amides, nitriles, amidines, thiosemicarbazones and guanylhydrazones) of 1H-benz[e]indene-2,3-dihydro-5-methyl-1-oxo-3-carboxylic acid and 1H-benz[e]indene-2,3-dihydro-7-methyl-3-oxo-1-carboxylic acid were prepared and tested for antiviral activities in vitro against vaccinia virus, HID stock and parainfluenza type 3 virus, HA-I/CR-8 stock. Four compounds (II g), (II i), (III b), (III g), showed weak activity in vitro against vaccinia virus.", "contents": "[Research on substances with antiviral activity. VIII. Benzindanoncarboxylic acids]. New derivatives (esters, amides, nitriles, amidines, thiosemicarbazones and guanylhydrazones) of 1H-benz[e]indene-2,3-dihydro-5-methyl-1-oxo-3-carboxylic acid and 1H-benz[e]indene-2,3-dihydro-7-methyl-3-oxo-1-carboxylic acid were prepared and tested for antiviral activities in vitro against vaccinia virus, HID stock and parainfluenza type 3 virus, HA-I/CR-8 stock. Four compounds (II g), (II i), (III b), (III g), showed weak activity in vitro against vaccinia virus."}
{"id": "PMID:204534", "title": "Peripheral nerves in early experimental diabetes: expansion of the endoneurial space as a cause of increased water content.", "content": "The aim of the present study was to examine whether the nerve water content and the Schwann cell cytoplasm are increased in early experimental diabetics, as suggested in the sorbitol theory. The sciatic nerves of streptozotocin diabetic rats were found to have an increased wet weight. The amount of Schwann cell cytoplasm was reduced by 30%. The increased wet weight was paralleled by enlargement of the cross sectional area of the nerve which was explained by an expansion of the endoneurial space. The findings indicate the existence of endoneurial oedema and are in part in conflict with the sorbitol theory. Extension of the space surrounding the nerve fibres may explain the increased resistance to ischaemia in diabetic patients.", "contents": "Peripheral nerves in early experimental diabetes: expansion of the endoneurial space as a cause of increased water content. The aim of the present study was to examine whether the nerve water content and the Schwann cell cytoplasm are increased in early experimental diabetics, as suggested in the sorbitol theory. The sciatic nerves of streptozotocin diabetic rats were found to have an increased wet weight. The amount of Schwann cell cytoplasm was reduced by 30%. The increased wet weight was paralleled by enlargement of the cross sectional area of the nerve which was explained by an expansion of the endoneurial space. The findings indicate the existence of endoneurial oedema and are in part in conflict with the sorbitol theory. Extension of the space surrounding the nerve fibres may explain the increased resistance to ischaemia in diabetic patients."}
{"id": "PMID:204535", "title": "Activation of human adenylate cyclase in the upper gastrointestinal tract by vasoactive intestinal polypeptide.", "content": "The effects of various polypeptide hormones known to inhibit gastric acid secretion were tested on the adenylate cyclase system in human gastric and duodenal mucosal homogenates. Glucagon and secretin failed to stimulate the enzyme system in the stomach. The latter hormone produced a small but significant activation of the duodenal cyclase. The vasoactive intestinal polypeptide (VIP), however, induced a dose-dependent increase of enzyme activity throughout the stomach and the duodenum. Maximal effects (1.8 to 3.0-fold increase) were observed at a VIP-concentration of about 10 microgram per ml. Because the entire physiological role of VIP in gastric function has not been defined, ipt cannot be discerned whether the VIP-stimulated adenylate cyclase is linked to inhibition of gastric acid secretion or to another as yet unrecognized effect of this hormone in human gastric function.", "contents": "Activation of human adenylate cyclase in the upper gastrointestinal tract by vasoactive intestinal polypeptide. The effects of various polypeptide hormones known to inhibit gastric acid secretion were tested on the adenylate cyclase system in human gastric and duodenal mucosal homogenates. Glucagon and secretin failed to stimulate the enzyme system in the stomach. The latter hormone produced a small but significant activation of the duodenal cyclase. The vasoactive intestinal polypeptide (VIP), however, induced a dose-dependent increase of enzyme activity throughout the stomach and the duodenum. Maximal effects (1.8 to 3.0-fold increase) were observed at a VIP-concentration of about 10 microgram per ml. Because the entire physiological role of VIP in gastric function has not been defined, ipt cannot be discerned whether the VIP-stimulated adenylate cyclase is linked to inhibition of gastric acid secretion or to another as yet unrecognized effect of this hormone in human gastric function."}
{"id": "PMID:204532", "title": "Abrogation of BCG-contact induced tumour inhibition by silica: implications for the mechanism of action.", "content": "The outgrowth of tumours from inocula of syngeneic rat tumour cells injected in admixture with BCG (Glaxo strain) is suppressed, the tumour cells apparently being destroyed in the milieu of the granulomatous reaction to the mycobacteria. The possible candidacy of macrophages as the major \"effector cell\" component was examined in experiments conducted in vivo using silica, a selective macrophage toxin. Intraperitoneal (i.p.) administration of this agent abolished contact-induced inhibition of BCG against three transplanted rat sarcomas, although for two of them the abrogatory effect could not be achieved without prior in vitro cultivation of the tumours. It is suggested that i.p. silica not only destroys macrophages within the cavity but accomplishes systemic depletion to the extent that granulomata contain insufficient macrophages for tumour rejection. This deficit may be compensated to a variable extent by the presence of host macrophages within the initial bacterial: tumour cell inoculum, but in the absence of these cells, total abrogation of the inhibitory effect of BCG is the invariable outcome in silica-treated hosts.", "contents": "Abrogation of BCG-contact induced tumour inhibition by silica: implications for the mechanism of action. The outgrowth of tumours from inocula of syngeneic rat tumour cells injected in admixture with BCG (Glaxo strain) is suppressed, the tumour cells apparently being destroyed in the milieu of the granulomatous reaction to the mycobacteria. The possible candidacy of macrophages as the major \"effector cell\" component was examined in experiments conducted in vivo using silica, a selective macrophage toxin. Intraperitoneal (i.p.) administration of this agent abolished contact-induced inhibition of BCG against three transplanted rat sarcomas, although for two of them the abrogatory effect could not be achieved without prior in vitro cultivation of the tumours. It is suggested that i.p. silica not only destroys macrophages within the cavity but accomplishes systemic depletion to the extent that granulomata contain insufficient macrophages for tumour rejection. This deficit may be compensated to a variable extent by the presence of host macrophages within the initial bacterial: tumour cell inoculum, but in the absence of these cells, total abrogation of the inhibitory effect of BCG is the invariable outcome in silica-treated hosts."}
{"id": "PMID:204536", "title": "Inhibition of VIP-stimulated intestinal secretion and cyclic AMP production by somatostatin in the rat.", "content": "The effect of somatostatin on colonic secretion induced by 10(-8) M vasoactive intestinal peptide (VIP), 10(-2) M theophylline, and 2 X 10(-3) M dibutyryl cyclic AMP was studied in muscle-stripped everted open rat colon sacs. The secretory response to VIP, measured as the decrease in net absorptive flow rate (microliters 30 min-1 mg-1 of dry weight), was maximal and equalled the responses to theophylline or dibutyryl cyclic AMP. Somatostatin (10(-5) M) blocked completely the secretory response to VIP but only partially the secretory response to theophylline or dibutyryl cyclic AMP. This difference in the extent of inhibition suggested that somatostatin exerted an inhibitory effect both before and after the point of generation of intracellular cyclic AMP. In order to test the hypothesis that one component of the action of somatostatin involved inhibition of the production of cyclic AMP, measurements of this nucleotide were made in isolated rat colon cells. Control levels of cyclic AMP measured by radioimmunoassay (12.6 +/- 1.6 pmoles per 10(6) cells) were not affected by 10(-5) M somatostatin. VIP (5 X 10(-8) M) increased cyclic AMP levels 2-fold (P less than 0.01) and this increase was blocked by somatostatin. The results indicated that somatostatin inhibits colonic secretion by exerting effects at two sites: one site lies at, and another beyond, the point of generation of intracellular cyclic AMP.", "contents": "Inhibition of VIP-stimulated intestinal secretion and cyclic AMP production by somatostatin in the rat. The effect of somatostatin on colonic secretion induced by 10(-8) M vasoactive intestinal peptide (VIP), 10(-2) M theophylline, and 2 X 10(-3) M dibutyryl cyclic AMP was studied in muscle-stripped everted open rat colon sacs. The secretory response to VIP, measured as the decrease in net absorptive flow rate (microliters 30 min-1 mg-1 of dry weight), was maximal and equalled the responses to theophylline or dibutyryl cyclic AMP. Somatostatin (10(-5) M) blocked completely the secretory response to VIP but only partially the secretory response to theophylline or dibutyryl cyclic AMP. This difference in the extent of inhibition suggested that somatostatin exerted an inhibitory effect both before and after the point of generation of intracellular cyclic AMP. In order to test the hypothesis that one component of the action of somatostatin involved inhibition of the production of cyclic AMP, measurements of this nucleotide were made in isolated rat colon cells. Control levels of cyclic AMP measured by radioimmunoassay (12.6 +/- 1.6 pmoles per 10(6) cells) were not affected by 10(-5) M somatostatin. VIP (5 X 10(-8) M) increased cyclic AMP levels 2-fold (P less than 0.01) and this increase was blocked by somatostatin. The results indicated that somatostatin inhibits colonic secretion by exerting effects at two sites: one site lies at, and another beyond, the point of generation of intracellular cyclic AMP."}
{"id": "PMID:204533", "title": "Mechanism of action of C. parvum on a solid, subcutaneous mouse tumour.", "content": "The effects of i.v. C. parvum on the growth of a.s.c. inoculum of the Lewis lung carcinoma were studied in normal C57 B1 mice, and in those in which separate components of the immune response were impaired. C. parvum given either at the same time as tumour inoculation or when the carcinoma was 1 cm in diameter, and fully vascularised, reduced tumour growth. Macrophages were impaired by silica (Si), cortisone acetate (CA) or trypan blue (TB), and T cells by thymectomy and sublethal irradiation (TXR) or antilymphocyte serum (ALS). TB did not affect tumour size, whereas Si, CA, TXR, or ALS (initiated before tumour inoculation) reduced it. When C. parvum was given in combination with TB, or ALS (initiated after tumour inoculation), its antitumour effects were unchanged. C. parvum given after ALS (before tumour), TXR, Si, or CA had no further effect on tumour growth. We have shown that C. parvum inhibits the growth of inoculated Lewis tumour. However, it has not been possible to clearly define in vivo the immunological mechanisms involved.", "contents": "Mechanism of action of C. parvum on a solid, subcutaneous mouse tumour. The effects of i.v. C. parvum on the growth of a.s.c. inoculum of the Lewis lung carcinoma were studied in normal C57 B1 mice, and in those in which separate components of the immune response were impaired. C. parvum given either at the same time as tumour inoculation or when the carcinoma was 1 cm in diameter, and fully vascularised, reduced tumour growth. Macrophages were impaired by silica (Si), cortisone acetate (CA) or trypan blue (TB), and T cells by thymectomy and sublethal irradiation (TXR) or antilymphocyte serum (ALS). TB did not affect tumour size, whereas Si, CA, TXR, or ALS (initiated before tumour inoculation) reduced it. When C. parvum was given in combination with TB, or ALS (initiated after tumour inoculation), its antitumour effects were unchanged. C. parvum given after ALS (before tumour), TXR, Si, or CA had no further effect on tumour growth. We have shown that C. parvum inhibits the growth of inoculated Lewis tumour. However, it has not been possible to clearly define in vivo the immunological mechanisms involved."}
{"id": "PMID:204543", "title": "Vagal stimulation and its role in eliciting gastrin but not glucagon release from the isolated perfused dog stomach.", "content": "Electrical stimulation (10 V, 10 Hz, 3 min) of both dorsal and ventral vagal trunks of the isolated canine stomach perfused with whole blood induced strong gastric contractions, transient release of cyclic GMP and marked release of gastrin. No gastric-glucagon release was elicited either at 'normal' (4.8 +/- 0.1 mmol/l) or at low (1.5 +/- 0.1 mmol/l) concentrations of blood glucose. It is concluded that, in conditions effective for the stimulation of gastrin release, electrical stimulation of the vagus nerves does not stimulate glucagon release from the isolated perfused dog stomach. Thus one of the well-accepted mechanisms controlling pancreatic-glucagon secretion, vagal stimulation, is ineffective on gastric-glucagon release.", "contents": "Vagal stimulation and its role in eliciting gastrin but not glucagon release from the isolated perfused dog stomach. Electrical stimulation (10 V, 10 Hz, 3 min) of both dorsal and ventral vagal trunks of the isolated canine stomach perfused with whole blood induced strong gastric contractions, transient release of cyclic GMP and marked release of gastrin. No gastric-glucagon release was elicited either at 'normal' (4.8 +/- 0.1 mmol/l) or at low (1.5 +/- 0.1 mmol/l) concentrations of blood glucose. It is concluded that, in conditions effective for the stimulation of gastrin release, electrical stimulation of the vagus nerves does not stimulate glucagon release from the isolated perfused dog stomach. Thus one of the well-accepted mechanisms controlling pancreatic-glucagon secretion, vagal stimulation, is ineffective on gastric-glucagon release."}
{"id": "PMID:204544", "title": "Plasma cyclic AMP levels during a secretin-caerulein pancreatic function test in liver and pancreatic disease.", "content": "Plasma cyclic AMP levels were determined during a 40 minute secretin infusion (1 Cl.U kg-1h-1) followed by a 40 minute combined secretin (1 Cl.U kg-1h-1) caerulein (75 ng kg-1h-1) infusion. In nine healthy subjects, both secretin alone and secretin in combination with caerulein did not affect plasma cyclic AMP levels. The same was observed in six patients with chronic pancreatitis. By contrast, in patients suffering from liver disease (nine cases) or extrahepatic cholestasis (six cases), secretin elicited large increases in plasma cyclic AMP concentration; the mean values attained being, respectively, seven and four times higher than before the infusion. On the other hand, increases in plasma cyclic AMP 10 minutes after a bolus injection of glucagon (1 mg) were four times lower in the liver disease group as compared to the controls. The results reported here suggest that the liver plays a major role in the degradation of plasma cyclic AMP produced by target tissues responding to secretin, and in the release of cyclic AMP under glucagon. Liver disease reduce the capacity of the liver to clear cyclic AMP from the blood. The pancreas does not contribute significantly to the cyclic AMP in the blood.", "contents": "Plasma cyclic AMP levels during a secretin-caerulein pancreatic function test in liver and pancreatic disease. Plasma cyclic AMP levels were determined during a 40 minute secretin infusion (1 Cl.U kg-1h-1) followed by a 40 minute combined secretin (1 Cl.U kg-1h-1) caerulein (75 ng kg-1h-1) infusion. In nine healthy subjects, both secretin alone and secretin in combination with caerulein did not affect plasma cyclic AMP levels. The same was observed in six patients with chronic pancreatitis. By contrast, in patients suffering from liver disease (nine cases) or extrahepatic cholestasis (six cases), secretin elicited large increases in plasma cyclic AMP concentration; the mean values attained being, respectively, seven and four times higher than before the infusion. On the other hand, increases in plasma cyclic AMP 10 minutes after a bolus injection of glucagon (1 mg) were four times lower in the liver disease group as compared to the controls. The results reported here suggest that the liver plays a major role in the degradation of plasma cyclic AMP produced by target tissues responding to secretin, and in the release of cyclic AMP under glucagon. Liver disease reduce the capacity of the liver to clear cyclic AMP from the blood. The pancreas does not contribute significantly to the cyclic AMP in the blood."}
{"id": "PMID:204550", "title": "Lymphoid cell lines: in vitro cell markers in correlation to tumorigenicity in nude mice.", "content": "Tumorigenicity of lymphoid cell lines of different origin upon xenotransplantation (s.c. and i.m.) in cell concentrations of 1 X 10(6) cell/inoculum into nude mice was correlated to karyotype, presence of the 14 q + marker, EBV reactivity and immunological markers. Lymphoblastoid cell lines (LCL), lacking the 14 q + marker failed to produce tumors independent upon diploidy or aneuploidy. Lymphoma-type lines of Burkitt lymphoma, lymphosarcoma and Hodgkins disease-origin, genotypically aneuploid, and expressing the 14 q + marker were tumorogenic in nude mice, when inoculated in the same cell quantities where LCL failed to form tumors. Tumorgrowth in nude mice was independent upon the presence of EBV in the inoculated cells.", "contents": "Lymphoid cell lines: in vitro cell markers in correlation to tumorigenicity in nude mice. Tumorigenicity of lymphoid cell lines of different origin upon xenotransplantation (s.c. and i.m.) in cell concentrations of 1 X 10(6) cell/inoculum into nude mice was correlated to karyotype, presence of the 14 q + marker, EBV reactivity and immunological markers. Lymphoblastoid cell lines (LCL), lacking the 14 q + marker failed to produce tumors independent upon diploidy or aneuploidy. Lymphoma-type lines of Burkitt lymphoma, lymphosarcoma and Hodgkins disease-origin, genotypically aneuploid, and expressing the 14 q + marker were tumorogenic in nude mice, when inoculated in the same cell quantities where LCL failed to form tumors. Tumorgrowth in nude mice was independent upon the presence of EBV in the inoculated cells."}
{"id": "PMID:204552", "title": "[Acupuncture as after care following injuries of the upper extremities].", "content": "Acupuncture is able to improve restriction of motion in general and in the smaller joints of the upper extremity, disturbances in circulation, posttraumatic swelling, reversible nerve lesions and ulcers following burns or pressure of a plaster. Localisation of the points for acupuncture in the different conditions and the possibilities of their combinations are described. Acupuncture is performed bilaterally at symmetrical points, unilaterally in pareses, contralaterally in amputees and in cases with dressings. During ear acupuncture the analgesic effect occurs more quickly, but has a shorter duration of action; in paralyses it was without success. The course of the treatment was controlled by clinical examination and measurement of the range of motion.", "contents": "[Acupuncture as after care following injuries of the upper extremities]. Acupuncture is able to improve restriction of motion in general and in the smaller joints of the upper extremity, disturbances in circulation, posttraumatic swelling, reversible nerve lesions and ulcers following burns or pressure of a plaster. Localisation of the points for acupuncture in the different conditions and the possibilities of their combinations are described. Acupuncture is performed bilaterally at symmetrical points, unilaterally in pareses, contralaterally in amputees and in cases with dressings. During ear acupuncture the analgesic effect occurs more quickly, but has a shorter duration of action; in paralyses it was without success. The course of the treatment was controlled by clinical examination and measurement of the range of motion."}
{"id": "PMID:204553", "title": "[Embryology and etiology of the Poland and Amazone syndromes].", "content": "In 1841 A. POLAND described a rare complex of malformations in the male, characterized a unilateral pectoral muscle defect combined with ipsilateral symbrachydaktyly. If in the female a POLAND Syndrome is associated with ipsilateral hypo- or aplasia of the breast as a leading feature, we propose to name this entity \"Amazone Syndrome\". Altogether 5 POLAND Syndromes and 40 \"Amazone Syndromes\" were seen in our department. For the latter a morphological grading into four groups was performed for clinical purposes. The malformation complex of the poland syndrome develops between the 2nd and 5th week of gestation as a result of damage to an upper extremity bud. It is from this extremity-\"Anlage\" that the muscles of the shoulder girdle and the lateral thoracic wall (with common innervation by the brachial plexus) arise. In early embryonal life the lacteal ridge lies in close proximity to the exrremity bud. The \"Amazone Syndrome\" can be explained by simultaneous damage to an extremity bud and the lacteal ridge. Its aetiology is not clear. Lack of embryonal material, heredity, and teratogenic damage by medication are discussed. In our patients there was a strong suspicion of unwanted pregnancies with failed induced interruptions. On the other hand some siblings had various other congenital deformities. In conclusion we may state that any inhibition of the normal growth of the upper extremity bud may lead to the POLAND Syndrome, while a simultaneous damage to the extremity bud and the close-by lacteal mound may result in the \"Amazone Syndrome.", "contents": "[Embryology and etiology of the Poland and Amazone syndromes]. In 1841 A. POLAND described a rare complex of malformations in the male, characterized a unilateral pectoral muscle defect combined with ipsilateral symbrachydaktyly. If in the female a POLAND Syndrome is associated with ipsilateral hypo- or aplasia of the breast as a leading feature, we propose to name this entity \"Amazone Syndrome\". Altogether 5 POLAND Syndromes and 40 \"Amazone Syndromes\" were seen in our department. For the latter a morphological grading into four groups was performed for clinical purposes. The malformation complex of the poland syndrome develops between the 2nd and 5th week of gestation as a result of damage to an upper extremity bud. It is from this extremity-\"Anlage\" that the muscles of the shoulder girdle and the lateral thoracic wall (with common innervation by the brachial plexus) arise. In early embryonal life the lacteal ridge lies in close proximity to the exrremity bud. The \"Amazone Syndrome\" can be explained by simultaneous damage to an extremity bud and the lacteal ridge. Its aetiology is not clear. Lack of embryonal material, heredity, and teratogenic damage by medication are discussed. In our patients there was a strong suspicion of unwanted pregnancies with failed induced interruptions. On the other hand some siblings had various other congenital deformities. In conclusion we may state that any inhibition of the normal growth of the upper extremity bud may lead to the POLAND Syndrome, while a simultaneous damage to the extremity bud and the close-by lacteal mound may result in the \"Amazone Syndrome."}
{"id": "PMID:204554", "title": "[Repeated contrast cisternography after previous use of an oily contrast medium (author's transl)].", "content": "Twenty-four control cisternograms were carried out at two to 22 months after lumbar injection of 1.0 to 1.5 ml. Duroliopaque; 20 of these were successfully performed without a fresh lumbar puncture. In most cases, the amount of contrast medium available was less than at the original examination, but was sufficient for definite exclusion of a space-occupying lesion. In four cases only the contrast medium could not be mobilised or manoeuvred into the cisterns and a fresh lumbar puncture was required for further contrast injection.", "contents": "[Repeated contrast cisternography after previous use of an oily contrast medium (author's transl)]. Twenty-four control cisternograms were carried out at two to 22 months after lumbar injection of 1.0 to 1.5 ml. Duroliopaque; 20 of these were successfully performed without a fresh lumbar puncture. In most cases, the amount of contrast medium available was less than at the original examination, but was sufficient for definite exclusion of a space-occupying lesion. In four cases only the contrast medium could not be mobilised or manoeuvred into the cisterns and a fresh lumbar puncture was required for further contrast injection."}
{"id": "PMID:204555", "title": "[In-flow of contrast into the liver--a rare complication during lymphography (author's transl)].", "content": "A lymphogram is described in which Lipiodol was found to have reached the liver from pelvic lymphatics. The common iliac and para-aortic lymph nodes had been invaded by tumour from a squamous carcinoma and this had produced complete lymphatic obstruction of the normal lymph paths. In addition, there was occlusion of the bifurcation of the iliac veins due to tumour, a finding also described by other authors. The causes for the finding of Lipiodol in the liver are discussed. The pathway by which the Lipiodol had reached the liver from the pelvic lymphatics, and the reaction of the liver parenchyma to the contrast medium, are considered.", "contents": "[In-flow of contrast into the liver--a rare complication during lymphography (author's transl)]. A lymphogram is described in which Lipiodol was found to have reached the liver from pelvic lymphatics. The common iliac and para-aortic lymph nodes had been invaded by tumour from a squamous carcinoma and this had produced complete lymphatic obstruction of the normal lymph paths. In addition, there was occlusion of the bifurcation of the iliac veins due to tumour, a finding also described by other authors. The causes for the finding of Lipiodol in the liver are discussed. The pathway by which the Lipiodol had reached the liver from the pelvic lymphatics, and the reaction of the liver parenchyma to the contrast medium, are considered."}
{"id": "PMID:204556", "title": "[The use of computer tomography for radiation therapy of cerebral tumours (author's transl)].", "content": "The application of computer tomography should be extended for indicating the need and choice of radiotherapy for cerebral tumours, and for observing the effects of treatment. In 26 patients it has been shown that CT is superior to conventional neuro-radiological methods in showing indications and in planning of radiation therapy. Forms of treatment can be suitably adapted where the histological type of the tumour is known. In most cerebral tumours, the beneficial effect of irradiation has been evident in our patients. Our criteria were based on the concept of \"clinical malignancy\", no attempt was made at a histological classification of the tumours.", "contents": "[The use of computer tomography for radiation therapy of cerebral tumours (author's transl)]. The application of computer tomography should be extended for indicating the need and choice of radiotherapy for cerebral tumours, and for observing the effects of treatment. In 26 patients it has been shown that CT is superior to conventional neuro-radiological methods in showing indications and in planning of radiation therapy. Forms of treatment can be suitably adapted where the histological type of the tumour is known. In most cerebral tumours, the beneficial effect of irradiation has been evident in our patients. Our criteria were based on the concept of \"clinical malignancy\", no attempt was made at a histological classification of the tumours."}
{"id": "PMID:204560", "title": "[Cytodiagnosis of the radiologically \"occult\" and the \"in situ\" lung neoplasm].", "content": "This paper reports on six patients, in whom a so-called \"carcinoma in situ\" or a radiologically \"occult\" carcinoma of the lung was diagnosed by means of cytological sputum examinations. On the basis of these cases, the problem of early localization of lung carcinomas is discussed. The cytological diagnosis of an occult lung carcinoma is practically always the result of an incidental sputum examination. Nevertheless, the value of \"mass screenings\" is doubtful, whereas systematic sputum examinations of so-called high risk patients seem so much the more indicated.", "contents": "[Cytodiagnosis of the radiologically \"occult\" and the \"in situ\" lung neoplasm]. This paper reports on six patients, in whom a so-called \"carcinoma in situ\" or a radiologically \"occult\" carcinoma of the lung was diagnosed by means of cytological sputum examinations. On the basis of these cases, the problem of early localization of lung carcinomas is discussed. The cytological diagnosis of an occult lung carcinoma is practically always the result of an incidental sputum examination. Nevertheless, the value of \"mass screenings\" is doubtful, whereas systematic sputum examinations of so-called high risk patients seem so much the more indicated."}
{"id": "PMID:204561", "title": "[Aspects of long-term therapy using long-term neuroleptics -- experiences and viewpoints related to practice].", "content": "Practical aspects of long-term neuroleptic therapy are discussed in the light of the author's own experience and observations; reference is made to the relevant literature. The author looks at the terms \"sociogenic\" and \"somatogenic\" in the context of treatment of schizophrenia and finds them to be not so antithetic as has traditionally been supposed. He describes the advantages and disadvantages of long-term neuroleptic therapy, both oral and injectable. He analyses the starting of a rational long-term therapy in the light of various factors. He examines the effective spectra of the traditional long-term neuroleptica and finds little justification for the different specific indications claimed for the various drugs. On the example of selected patients suitable for this therapy he considers the causes of the disorders and the primary personality and early development of the subjects, discussing the nature of the illness from the nosological and clinical point of view, the social and economic situations, the type of follow-up, and the physician-patient relationship. Emphasis is laid on the significance of side-effects and of individual reactions to long-term neuroleptics. The questions how, when and where a patient should be put onto long-term medication are treated, with a critical comparison of high and traditional doses, and a recommendation that duration and stoppage of therapy be decided on the basis of individual case factors. Special attention is paid to the so-called pharmacogenic depressions. Other indications of long-term neuroleptic therapy are mentioned. The author considers the integration of pharmaco-therapy into a complex rehabilitation program to be essential; without this there can be no progress in the treatment of schizophrenia.", "contents": "[Aspects of long-term therapy using long-term neuroleptics -- experiences and viewpoints related to practice]. Practical aspects of long-term neuroleptic therapy are discussed in the light of the author's own experience and observations; reference is made to the relevant literature. The author looks at the terms \"sociogenic\" and \"somatogenic\" in the context of treatment of schizophrenia and finds them to be not so antithetic as has traditionally been supposed. He describes the advantages and disadvantages of long-term neuroleptic therapy, both oral and injectable. He analyses the starting of a rational long-term therapy in the light of various factors. He examines the effective spectra of the traditional long-term neuroleptica and finds little justification for the different specific indications claimed for the various drugs. On the example of selected patients suitable for this therapy he considers the causes of the disorders and the primary personality and early development of the subjects, discussing the nature of the illness from the nosological and clinical point of view, the social and economic situations, the type of follow-up, and the physician-patient relationship. Emphasis is laid on the significance of side-effects and of individual reactions to long-term neuroleptics. The questions how, when and where a patient should be put onto long-term medication are treated, with a critical comparison of high and traditional doses, and a recommendation that duration and stoppage of therapy be decided on the basis of individual case factors. Special attention is paid to the so-called pharmacogenic depressions. Other indications of long-term neuroleptic therapy are mentioned. The author considers the integration of pharmaco-therapy into a complex rehabilitation program to be essential; without this there can be no progress in the treatment of schizophrenia."}
{"id": "PMID:204562", "title": "[Clinicopathological study of diffuse carcinoma of stomach (author's transl)].", "content": "The biological behavior of ulcer type gastric carcinoma was studied on 114 cases of diffuse carcinoma (Borrmann's 4 type) and 262 cases of early like advanced carcinoma (including superficial spreading type). In both types of gastric carcinoma, the age distribution, location, ulcer with cancer focus and prognosis differed greatly. The early like carcinoma was speculated to have advanced maintaining the groos findings of early gastric carcinoma, and its location and associated ulcer were the same as the early ulcer type of carcinoma. The prognosis of this type of carcinoma was good, showing a figure of 70% in 3 year survival rate. On the other hand, diffuse carcinoma demonstrated diffuse extensive infiltration of tumor cells along the gastric wall, resulting in poor prognosis with a 3 year survival rate of almost 0%. Histologically, diffuse type of carcinoma showed lymphatic infiltration of tumor cells, and this is probably the main reason for the diffuse infiltration in this type of carcinoma. Diffuse carcinoma is, therefore, considered to be one special type of carcinoma having different biological behavior compared with the other ulcer type of carcinoma, and diffuse carcinoma is not the terminal stage of early like advanced carcinoma. There are three stages in diffuse carcinoma: 1. Infiltrative stage: wide spread infiltration of cancer cells through lymphatic channels (lymphangiosis carcinomatosa) 2. Edematous stage: soluble collagen appearing in gastric wall 3. Sclerosing stage: soluble collagen changing into insoluble collagen leading to marked thickening and stiffness of the gastric wall. This is the end stage of gastric diffuse carcinoma. It is difficult to explain that the marked fibrosis of gastric wall is a result to stromal reaction from tumor cell infiltration, since extensive fibrosis is found in areas without tumor cells and stiffness of the gastric wall occurs in a too short period of time. The production of abundunt soluble collagen is probably related to cancer cells.", "contents": "[Clinicopathological study of diffuse carcinoma of stomach (author's transl)]. The biological behavior of ulcer type gastric carcinoma was studied on 114 cases of diffuse carcinoma (Borrmann's 4 type) and 262 cases of early like advanced carcinoma (including superficial spreading type). In both types of gastric carcinoma, the age distribution, location, ulcer with cancer focus and prognosis differed greatly. The early like carcinoma was speculated to have advanced maintaining the groos findings of early gastric carcinoma, and its location and associated ulcer were the same as the early ulcer type of carcinoma. The prognosis of this type of carcinoma was good, showing a figure of 70% in 3 year survival rate. On the other hand, diffuse carcinoma demonstrated diffuse extensive infiltration of tumor cells along the gastric wall, resulting in poor prognosis with a 3 year survival rate of almost 0%. Histologically, diffuse type of carcinoma showed lymphatic infiltration of tumor cells, and this is probably the main reason for the diffuse infiltration in this type of carcinoma. Diffuse carcinoma is, therefore, considered to be one special type of carcinoma having different biological behavior compared with the other ulcer type of carcinoma, and diffuse carcinoma is not the terminal stage of early like advanced carcinoma. There are three stages in diffuse carcinoma: 1. Infiltrative stage: wide spread infiltration of cancer cells through lymphatic channels (lymphangiosis carcinomatosa) 2. Edematous stage: soluble collagen appearing in gastric wall 3. Sclerosing stage: soluble collagen changing into insoluble collagen leading to marked thickening and stiffness of the gastric wall. This is the end stage of gastric diffuse carcinoma. It is difficult to explain that the marked fibrosis of gastric wall is a result to stromal reaction from tumor cell infiltration, since extensive fibrosis is found in areas without tumor cells and stiffness of the gastric wall occurs in a too short period of time. The production of abundunt soluble collagen is probably related to cancer cells."}
{"id": "PMID:204564", "title": "Urinary and plasma cyclic AMP levels during short term starvation in obese man: response to glucagon stimulation.", "content": "Glucagon is known to elevate the intracellular concentration of cyclic AMP in the hepatocyte. The increase in intracellular cyclic AMP is reflected by an increase in the plasma concentration of the nucleotide. Intravenous glucagon stimulation was performed on six obese non-diabetic human subjects before and after a three day fast. All patients responded to starvation by a lowering of plasma immunoreactive insulin and blood glucose. Whereas the plasma immunoreactive glucagon concentration increased over the three day period, the plasma and urinary cyclic AMP did not significantly change. Intravenous glucagon promoted qualitatively similar increases in the blood glucose and plasma concentrations of insulin and cyclic AMP before and after three days starvation.", "contents": "Urinary and plasma cyclic AMP levels during short term starvation in obese man: response to glucagon stimulation. Glucagon is known to elevate the intracellular concentration of cyclic AMP in the hepatocyte. The increase in intracellular cyclic AMP is reflected by an increase in the plasma concentration of the nucleotide. Intravenous glucagon stimulation was performed on six obese non-diabetic human subjects before and after a three day fast. All patients responded to starvation by a lowering of plasma immunoreactive insulin and blood glucose. Whereas the plasma immunoreactive glucagon concentration increased over the three day period, the plasma and urinary cyclic AMP did not significantly change. Intravenous glucagon promoted qualitatively similar increases in the blood glucose and plasma concentrations of insulin and cyclic AMP before and after three days starvation."}
{"id": "PMID:204566", "title": "Effect of treadmill exercise on plasma and urinary cyclic adenosine 3'5'-monophosphate.", "content": "The effect of treadmill exercise on plasma and urinary cyclic adenosine 3'5' monophosphate levels (cyclic AMP) was studied in twelve healthy subjects. Plasma cyclic AMP levels were found to be markedly elevated without significant changes in urinary cyclic AMP or cyclic AMP/creatine ratio. Most likely altered plasma glucagon and catecholamine levels were responsible for these changes.", "contents": "Effect of treadmill exercise on plasma and urinary cyclic adenosine 3'5'-monophosphate. The effect of treadmill exercise on plasma and urinary cyclic adenosine 3'5' monophosphate levels (cyclic AMP) was studied in twelve healthy subjects. Plasma cyclic AMP levels were found to be markedly elevated without significant changes in urinary cyclic AMP or cyclic AMP/creatine ratio. Most likely altered plasma glucagon and catecholamine levels were responsible for these changes."}
{"id": "PMID:204567", "title": "Plasma renin activity and urinary aldosterone in Cushing's syndrome.", "content": "The renin-angiotensin-aldosterone system has been evaluated in 19 patients with Cushing's syndrome due to bilateral adrenal hyperplasia and in 2 patients with unilateral adenoma. In the first group urinary aldosterone was within the normal limits with a mean of 8.3 +/- 1.86 microgram/24 h. Aldosterone excretion did not change significantly after furosemide administration, ACTH infusion or dexamethasone. Upright PRA was suppressed in 9/16 patients with a mean of 4.9 +/- 1.85 ng/ml/3 h and showed only a slight response to furosemide. Dexamethasone alone did not produce any change. Both aldosterone and PRA were to some extent stimulated by an association of dexamethasone and furosemide. In the 2 patients with adenoma, aldosterone excretion was also normal, but PRA was very elevated. From our data it is concluded that in Cushing's syndrome due to bilateral hyperplasia, PRA and aldosterone excretion are partially suppressed. From our results on plasma deoxycorticosterone and corticosterone concentration it seems unlikely that these mineralocorticoids are the major cause of this phenomenon. However, it may not be excluded that other yet unidentified hormones could play some role in the pathogenesis of hypertension and renin suppression in Cushing's syndrome.", "contents": "Plasma renin activity and urinary aldosterone in Cushing's syndrome. The renin-angiotensin-aldosterone system has been evaluated in 19 patients with Cushing's syndrome due to bilateral adrenal hyperplasia and in 2 patients with unilateral adenoma. In the first group urinary aldosterone was within the normal limits with a mean of 8.3 +/- 1.86 microgram/24 h. Aldosterone excretion did not change significantly after furosemide administration, ACTH infusion or dexamethasone. Upright PRA was suppressed in 9/16 patients with a mean of 4.9 +/- 1.85 ng/ml/3 h and showed only a slight response to furosemide. Dexamethasone alone did not produce any change. Both aldosterone and PRA were to some extent stimulated by an association of dexamethasone and furosemide. In the 2 patients with adenoma, aldosterone excretion was also normal, but PRA was very elevated. From our data it is concluded that in Cushing's syndrome due to bilateral hyperplasia, PRA and aldosterone excretion are partially suppressed. From our results on plasma deoxycorticosterone and corticosterone concentration it seems unlikely that these mineralocorticoids are the major cause of this phenomenon. However, it may not be excluded that other yet unidentified hormones could play some role in the pathogenesis of hypertension and renin suppression in Cushing's syndrome."}
{"id": "PMID:204569", "title": "A program for continuing care: implementation and outcome.", "content": "The authors used the records of the continuing-care program at a large public hospital in Los Angeles to determine the success of referrals for aftercare. A total of 552 patients discharged during an eight-month period were referred for continuing care; 418 of the patients kept their first appointment. Patients were most likely to keep their first appointment if it was set up for within three days of release from the hospital and if it was confirmed before discharge from the hospital. If an appointment could not be arranged within three days, a phone call to the patient improved the referral completion rate.", "contents": "A program for continuing care: implementation and outcome. The authors used the records of the continuing-care program at a large public hospital in Los Angeles to determine the success of referrals for aftercare. A total of 552 patients discharged during an eight-month period were referred for continuing care; 418 of the patients kept their first appointment. Patients were most likely to keep their first appointment if it was set up for within three days of release from the hospital and if it was confirmed before discharge from the hospital. If an appointment could not be arranged within three days, a phone call to the patient improved the referral completion rate."}
{"id": "PMID:204572", "title": "Tumor immunity: relevance of animal models to man.", "content": "The conclusions that can be drawn from results of animal experiments often provide important insights into the mechanisms of human disease and the rationale for effective therapy. A few years ago, animal models of tumor immunity revealed that both specific and nonimmune specific stimulation of the immune system could effectively prevent or cure cancer. Extensive clinical studies have not convincingly demonstrated that the results with the animal models used are reproducible in humans. New animal models more closely reflecting the properties of human cancer are needed to determine the applicability of cancer immunotherapy to man.", "contents": "Tumor immunity: relevance of animal models to man. The conclusions that can be drawn from results of animal experiments often provide important insights into the mechanisms of human disease and the rationale for effective therapy. A few years ago, animal models of tumor immunity revealed that both specific and nonimmune specific stimulation of the immune system could effectively prevent or cure cancer. Extensive clinical studies have not convincingly demonstrated that the results with the animal models used are reproducible in humans. New animal models more closely reflecting the properties of human cancer are needed to determine the applicability of cancer immunotherapy to man."}
{"id": "PMID:204574", "title": "The importance of the ratio between effector and target cells for detection of serum blocking of tumor lymphocytolysis.", "content": "Sera from tumor-bearong guinea pigs were tested for their capacity to influence the magnitude of lymphocytolysis of tumor cells in vitro as measured by 51Cr release. Thirty-three sera were tested in 124 experiments in which the effector to target cell ratio (E:T) was 200:1. Significant blocking of cell-mediated lysis occurred in 62% of the experiments, whereas significant potentiation occurred in 7%. Six sera were found which showed significant blocking in some experiments and significant potentiation in other experiments. One of these sera was further evaluated by varying E:T, using lymphocytes from three immune donors. For each of the three populations of immune lymphocytes, significant blocking was demostrable only at one of three E:T tested. Blocking was observed only with an E:T of 200:1 in two cases. In a third case, blocking was observed at an E:T of 50:1, whereas an E:T of 200:1 gave rise to significant potentiation. The effect of these sera on lymphocytolysis in vitro is clearly dependent upon the E:T ratio.", "contents": "The importance of the ratio between effector and target cells for detection of serum blocking of tumor lymphocytolysis. Sera from tumor-bearong guinea pigs were tested for their capacity to influence the magnitude of lymphocytolysis of tumor cells in vitro as measured by 51Cr release. Thirty-three sera were tested in 124 experiments in which the effector to target cell ratio (E:T) was 200:1. Significant blocking of cell-mediated lysis occurred in 62% of the experiments, whereas significant potentiation occurred in 7%. Six sera were found which showed significant blocking in some experiments and significant potentiation in other experiments. One of these sera was further evaluated by varying E:T, using lymphocytes from three immune donors. For each of the three populations of immune lymphocytes, significant blocking was demostrable only at one of three E:T tested. Blocking was observed only with an E:T of 200:1 in two cases. In a third case, blocking was observed at an E:T of 50:1, whereas an E:T of 200:1 gave rise to significant potentiation. The effect of these sera on lymphocytolysis in vitro is clearly dependent upon the E:T ratio."}
{"id": "PMID:204579", "title": "Reactivation of latent herpes simplex virus infection of the autonomic nervous system by postganglionic neurectomy.", "content": "Latent herpes simplex virus infection of the superior cervical autonomic ganglion was reactivated in vivo by postganglionic neurectomy. Two methods were used to demonstrate viral reactivation: (i) recovery of infectious herpes simplex virus in ganglion homogenates and (ii) acceleration of virus expression in ganglion explants in culture. Both the percentage of mice exhibiting reactivated ganglion infection and the viral titers detected in ganglia increased when neurectomized mice were treated with cyclophosphamide. Antithymocyte serum treatment prolonged the time course over which neurectomy-induced virus could be detected, but neither antithymocyte serum nor cyclophosphamide reactivated herpes simplex virus in the absence of neurectomy. These results demonstrate that postganlionic neurectomy provides a specific stimulus for herpes simplex virus reactivation and that cell-mediated immune defense are involved in the highly efficient elimination of reactivated virus from the ganglion in vivo.", "contents": "Reactivation of latent herpes simplex virus infection of the autonomic nervous system by postganglionic neurectomy. Latent herpes simplex virus infection of the superior cervical autonomic ganglion was reactivated in vivo by postganglionic neurectomy. Two methods were used to demonstrate viral reactivation: (i) recovery of infectious herpes simplex virus in ganglion homogenates and (ii) acceleration of virus expression in ganglion explants in culture. Both the percentage of mice exhibiting reactivated ganglion infection and the viral titers detected in ganglia increased when neurectomized mice were treated with cyclophosphamide. Antithymocyte serum treatment prolonged the time course over which neurectomy-induced virus could be detected, but neither antithymocyte serum nor cyclophosphamide reactivated herpes simplex virus in the absence of neurectomy. These results demonstrate that postganlionic neurectomy provides a specific stimulus for herpes simplex virus reactivation and that cell-mediated immune defense are involved in the highly efficient elimination of reactivated virus from the ganglion in vivo."}
{"id": "PMID:204580", "title": "Search for latent cytomegalovirus in renal allografts.", "content": "Cytomegalovirus (CMV) infection is common after renal transplantation, and cytomegaloviruria occurs in about two-thirds of the recipients. These observations suggest that the allografts may be a site of latent infection with CMV and its reactivation may be the source of viruria. To investigate this possibility, 130 kidney specimens from 85 persons were cultured, and simultaneous explants were made of 63 of them from 50 people. No CMV was received from 33 normal kidney or cadaver donors or from 19 allograft recipients who had no evidence of posttransplantation infection with CMV. The experiment included 37 primary organ explants that yielded no evidence of latent virus. Among 33 allograft recipients with posttransplantation CMV infection, overt infectious virus was isolated from 6 of 57 allograft biopsies. All six positive specimens were from four patients, all of whom had viruria simultaneously. Organ explants from 20 of the recipients with demonstrated postoperative CMV infection, including 13 viruric patients, failed to unmask any latent CMV. Thus, allograft kidneys were infrequently infected with CMV (6%), even in patients with viruria (24%). The kidney parenchyma appears to be an uncommon site of latent CMV infection and may not be the usual source of virus in patients with viruria.", "contents": "Search for latent cytomegalovirus in renal allografts. Cytomegalovirus (CMV) infection is common after renal transplantation, and cytomegaloviruria occurs in about two-thirds of the recipients. These observations suggest that the allografts may be a site of latent infection with CMV and its reactivation may be the source of viruria. To investigate this possibility, 130 kidney specimens from 85 persons were cultured, and simultaneous explants were made of 63 of them from 50 people. No CMV was received from 33 normal kidney or cadaver donors or from 19 allograft recipients who had no evidence of posttransplantation infection with CMV. The experiment included 37 primary organ explants that yielded no evidence of latent virus. Among 33 allograft recipients with posttransplantation CMV infection, overt infectious virus was isolated from 6 of 57 allograft biopsies. All six positive specimens were from four patients, all of whom had viruria simultaneously. Organ explants from 20 of the recipients with demonstrated postoperative CMV infection, including 13 viruric patients, failed to unmask any latent CMV. Thus, allograft kidneys were infrequently infected with CMV (6%), even in patients with viruria (24%). The kidney parenchyma appears to be an uncommon site of latent CMV infection and may not be the usual source of virus in patients with viruria."}
{"id": "PMID:204581", "title": "Pivmecillinam treatment of chronic urinary tract infection.", "content": "Twenty-eight patients with chronic urinary tract infections were treated with 400 mg pivmecillinam orally three times daily for 10 to 15 days. The diagnosis was confirmed by a history of cystitis or cystopyelitis four to six times annually, microscopy of urine sediment, and growth of pathogens in urine specimens obtained by suprapubic bladder puncture. Three days, three and six weeks after completion of therapy the success rates were 24/28, 20/28 and 19/28 respectively. Pivmecillinam was well tolerated. Two patients developed nausea and vomiting. Other side-effects were not observed. Pivmecillinam is a useful drug in the treatment of chronic urinary tract infections.", "contents": "Pivmecillinam treatment of chronic urinary tract infection. Twenty-eight patients with chronic urinary tract infections were treated with 400 mg pivmecillinam orally three times daily for 10 to 15 days. The diagnosis was confirmed by a history of cystitis or cystopyelitis four to six times annually, microscopy of urine sediment, and growth of pathogens in urine specimens obtained by suprapubic bladder puncture. Three days, three and six weeks after completion of therapy the success rates were 24/28, 20/28 and 19/28 respectively. Pivmecillinam was well tolerated. Two patients developed nausea and vomiting. Other side-effects were not observed. Pivmecillinam is a useful drug in the treatment of chronic urinary tract infections."}
{"id": "PMID:204582", "title": "Effect of immunization on the cyclic AMP level and 3H-thymidine incorporation in cultured lymphoid cells.", "content": "The cyclic AMP level and the uptake of 3H-thymidine were studied in short-term suspension cultures of guinea pig lymphoid cells. Spleen cells from animals immunized 3 days previously with typhoid vaccine were shown to differ in three respects from the normal cells: (1) The level of cyclic AMP was higher. (2) The cyclic AMP increase following addition of isoproterenol or adenosine was abolished. (3) Isoproterenol (10(-5) to 10(-4) M) stimulated the uptake of 3H-thymidine in cells from immunized animals, while the uptake into normal cells was inhibited by these concentrations. A higher dose of isoproterenol (10(-3) M) inhibited 3H-thymidine uptake in both immunized and normal cells. The results reveal certain biochemical alterations in splenic lymphocytes after immunization. An altered 3H-thymidine uptake may be caused by the modified cyclic AMP metabolism in cells from immunized animals.", "contents": "Effect of immunization on the cyclic AMP level and 3H-thymidine incorporation in cultured lymphoid cells. The cyclic AMP level and the uptake of 3H-thymidine were studied in short-term suspension cultures of guinea pig lymphoid cells. Spleen cells from animals immunized 3 days previously with typhoid vaccine were shown to differ in three respects from the normal cells: (1) The level of cyclic AMP was higher. (2) The cyclic AMP increase following addition of isoproterenol or adenosine was abolished. (3) Isoproterenol (10(-5) to 10(-4) M) stimulated the uptake of 3H-thymidine in cells from immunized animals, while the uptake into normal cells was inhibited by these concentrations. A higher dose of isoproterenol (10(-3) M) inhibited 3H-thymidine uptake in both immunized and normal cells. The results reveal certain biochemical alterations in splenic lymphocytes after immunization. An altered 3H-thymidine uptake may be caused by the modified cyclic AMP metabolism in cells from immunized animals."}
{"id": "PMID:204583", "title": "Establishment of paired tumor cells and autologous virus-transformed cell lines to define humoral immune responses in melanoma and sarcoma patients.", "content": "Peripheral blood lymphocytes and skin fibroblasts from 12 cancer patients were infected with Epstein-Barr virus (EBV) or SV40 virus. The EBV-transformed lymphoblasts and SV40-transformed fibroblasts were grown as continuous cell lines and expressed the same histocompatibility antigens as tumor cell lines established from the same cancer patients. Sera from 350 melanoma and 195 sarcoma patients were tested for antibody reactive with membrane antigens on three of these tumor cell lines (two melanomas and one sarcoma) by immune adherence (IA) and indirect immunofluorescence (IMI) assays. Antibodies to HLA and other non-tumor-related antigens were completely removed from the most reactive sera by quantitative absorption with 4 x 10(7) lymphoblasts or 10(7) transformed fibroblasts autologous to the tumor target cells. These paired cell lines were used to monitor humoral immune responses in melanoma and sarcoma patients receiving allogeneic tumor cell vaccines.", "contents": "Establishment of paired tumor cells and autologous virus-transformed cell lines to define humoral immune responses in melanoma and sarcoma patients. Peripheral blood lymphocytes and skin fibroblasts from 12 cancer patients were infected with Epstein-Barr virus (EBV) or SV40 virus. The EBV-transformed lymphoblasts and SV40-transformed fibroblasts were grown as continuous cell lines and expressed the same histocompatibility antigens as tumor cell lines established from the same cancer patients. Sera from 350 melanoma and 195 sarcoma patients were tested for antibody reactive with membrane antigens on three of these tumor cell lines (two melanomas and one sarcoma) by immune adherence (IA) and indirect immunofluorescence (IMI) assays. Antibodies to HLA and other non-tumor-related antigens were completely removed from the most reactive sera by quantitative absorption with 4 x 10(7) lymphoblasts or 10(7) transformed fibroblasts autologous to the tumor target cells. These paired cell lines were used to monitor humoral immune responses in melanoma and sarcoma patients receiving allogeneic tumor cell vaccines."}
{"id": "PMID:204584", "title": "The frequency of occurrence of feline leukaemia virus subgroups in cats.", "content": "Feline leukaemia viruses (FeLV) were isolated from cats in Glasgow and New York with lymphosarcoma and from apparently healthy carrier cats. The subgroup composition of each isolate was determined. All isolates contained FeLV of subgroup A(FeLV-A) and a high proportion also contained subgroup B virus (FeLV-B). Virus of subgroup C (FeLV-C) was rare and occurred in association with FeLV-A and, in some isolates, with FeLV-B as well. The same pattern was observed in isolates from British and American cats. The frequency of FeLV subgroups was different in cats with lymphosarcoma and in healthy carrier cats. In cats with lymphosarcoma, 42% had FeLV-A and 58% had FeLV-AB; there was no obvious correlation between virus subgroup and type of disease. In FeLV-positive healthy cats, 65% had FeLV-A and 33% had FeLV-AB. FeLV-C was isolated only from cats with disease. The healthy carrier cats were from multiple-cat households (MCH). Two distinct types of FeLV-infected MCH were found: MCH-A in which the carrier cats yielded only FeLV-A, and MCH-AB in which cats with either FeLV-A or FeLV-AB were present. In MCH-AB half of the cats had FeLV-A and half had FeLV-AB. Overall, the proportion of cats in MCH which were viraemic with FeLV was 42%. However, there was a marked difference in the prevalence of carrier cats in each type of MCH: in MCH-A, 28% were FeLV-positive while in MCH-AB, 53% were viraemic.", "contents": "The frequency of occurrence of feline leukaemia virus subgroups in cats. Feline leukaemia viruses (FeLV) were isolated from cats in Glasgow and New York with lymphosarcoma and from apparently healthy carrier cats. The subgroup composition of each isolate was determined. All isolates contained FeLV of subgroup A(FeLV-A) and a high proportion also contained subgroup B virus (FeLV-B). Virus of subgroup C (FeLV-C) was rare and occurred in association with FeLV-A and, in some isolates, with FeLV-B as well. The same pattern was observed in isolates from British and American cats. The frequency of FeLV subgroups was different in cats with lymphosarcoma and in healthy carrier cats. In cats with lymphosarcoma, 42% had FeLV-A and 58% had FeLV-AB; there was no obvious correlation between virus subgroup and type of disease. In FeLV-positive healthy cats, 65% had FeLV-A and 33% had FeLV-AB. FeLV-C was isolated only from cats with disease. The healthy carrier cats were from multiple-cat households (MCH). Two distinct types of FeLV-infected MCH were found: MCH-A in which the carrier cats yielded only FeLV-A, and MCH-AB in which cats with either FeLV-A or FeLV-AB were present. In MCH-AB half of the cats had FeLV-A and half had FeLV-AB. Overall, the proportion of cats in MCH which were viraemic with FeLV was 42%. However, there was a marked difference in the prevalence of carrier cats in each type of MCH: in MCH-A, 28% were FeLV-positive while in MCH-AB, 53% were viraemic."}
{"id": "PMID:204588", "title": "Design of a photoaffinity label for the hormone binding site of neurophysin.", "content": "The photolabile peptide, L-methionyl-L-tyrosyl-p-azido-L-phenylalaninamide, was synthesized by solution methods. This peptide, as well as the analogous species containing tritiated methionine, were found to bind reversibly and specifically, in the dark, to bovine neurophysin II. The dissociation constant, stoichiometry, and pH-dependence of this noncovalent interaction are typical of those properties for hormone (oxytocin) and hormone-like ligand binding to neurophysin II. Under photolytic conditions, methionyl-tyrosyl-p-azidophenylalaninamide causes irreversible inhibition of the noncovalent ligand binding activity of neurophysin II. This inactivation was achieved to the extent of about 90%. Both the dark and light (photolytic) interactions of the photolabile peptide with neurophysin II indicate its reaction at the hormone binding site of the protein and thus its potential use to identify amino acid residues at this site by covalent photoaffinity labelling.", "contents": "Design of a photoaffinity label for the hormone binding site of neurophysin. The photolabile peptide, L-methionyl-L-tyrosyl-p-azido-L-phenylalaninamide, was synthesized by solution methods. This peptide, as well as the analogous species containing tritiated methionine, were found to bind reversibly and specifically, in the dark, to bovine neurophysin II. The dissociation constant, stoichiometry, and pH-dependence of this noncovalent interaction are typical of those properties for hormone (oxytocin) and hormone-like ligand binding to neurophysin II. Under photolytic conditions, methionyl-tyrosyl-p-azidophenylalaninamide causes irreversible inhibition of the noncovalent ligand binding activity of neurophysin II. This inactivation was achieved to the extent of about 90%. Both the dark and light (photolytic) interactions of the photolabile peptide with neurophysin II indicate its reaction at the hormone binding site of the protein and thus its potential use to identify amino acid residues at this site by covalent photoaffinity labelling."}
{"id": "PMID:204590", "title": "Radical formation in single crystals of hypoxanthine.HCl.H2O, inosine, and the disodium salt of 5'-inosine-monophosphate.", "content": "Radical formation in single crystals of hypoxanthine.HCl.H2O, inosine and Na2-5'-IMP.(7.5 H2O) by X-irradiation has been studied using electron-spin-resonance spectroscopy at 9.5 and 35 GHz. In all crystals both H-addition radicals at position C2 and C8 of the purine ring are found. The coupling constants of these two radicals are different and depend strongly on the protonation state of the base. INDO-calculations indicate that the C8-radical is protonated at O6. In Na2-5'-IMP OH-addition radicals at position C2 of the purine ring are formed. Electron adduct radicals are found in the neutral and the N7-protonated base after X-irradiation at 77 K. In Na2-5'-IMP no electron adduct is formed but a radical which probably is the cation. In hypoxanthine.HCl.H2O a radical could be observed after X-irradiation at 77 K, which results from addition of a Cl- to the nitrogen N1.", "contents": "Radical formation in single crystals of hypoxanthine.HCl.H2O, inosine, and the disodium salt of 5'-inosine-monophosphate. Radical formation in single crystals of hypoxanthine.HCl.H2O, inosine and Na2-5'-IMP.(7.5 H2O) by X-irradiation has been studied using electron-spin-resonance spectroscopy at 9.5 and 35 GHz. In all crystals both H-addition radicals at position C2 and C8 of the purine ring are found. The coupling constants of these two radicals are different and depend strongly on the protonation state of the base. INDO-calculations indicate that the C8-radical is protonated at O6. In Na2-5'-IMP OH-addition radicals at position C2 of the purine ring are formed. Electron adduct radicals are found in the neutral and the N7-protonated base after X-irradiation at 77 K. In Na2-5'-IMP no electron adduct is formed but a radical which probably is the cation. In hypoxanthine.HCl.H2O a radical could be observed after X-irradiation at 77 K, which results from addition of a Cl- to the nitrogen N1."}
{"id": "PMID:204586", "title": "Sensory testing: a sensitive method in the follow-up of nerve involvement.", "content": "Sensory testing (ST) as a parameter in assessing nerve damage and as a guide in anti-reaction treatment is discussed in comparison with established methods like voluntary muscle testing (VMT) and motor nerve conduction velocity (MCV). Sensory testing is shown to be a valuable addition to the existing tests and may even be used as a single parameter.", "contents": "Sensory testing: a sensitive method in the follow-up of nerve involvement. Sensory testing (ST) as a parameter in assessing nerve damage and as a guide in anti-reaction treatment is discussed in comparison with established methods like voluntary muscle testing (VMT) and motor nerve conduction velocity (MCV). Sensory testing is shown to be a valuable addition to the existing tests and may even be used as a single parameter."}
{"id": "PMID:204591", "title": "The action of ionizing radiation on protein. III. Radical formation in L-phenylalanine.HCl.", "content": "The radicals produced by X-irradiation in L-phenylalanine.HCl crystals have been analysed by electron-spin-resonance (e.s.r.) spectroscopy. Four radicals have been identified: the radical resulting from electron capture by the carboxylic group, the radical resulting from deamination, an hydrogen addition radical to the benzene ring, and the radical resulting from hydrogen abstraction from the methylene group bonded to Cbeta. These identifications are supported by INDO calculations.", "contents": "The action of ionizing radiation on protein. III. Radical formation in L-phenylalanine.HCl. The radicals produced by X-irradiation in L-phenylalanine.HCl crystals have been analysed by electron-spin-resonance (e.s.r.) spectroscopy. Four radicals have been identified: the radical resulting from electron capture by the carboxylic group, the radical resulting from deamination, an hydrogen addition radical to the benzene ring, and the radical resulting from hydrogen abstraction from the methylene group bonded to Cbeta. These identifications are supported by INDO calculations."}
{"id": "PMID:204592", "title": "The interaction of cytochrome C with phospholipids. A pulse-radiolysis study.", "content": "The reactions of the hydrated electron (eaq-), produced during pulse radiolysis, have been used to study the binding of phosphatidyl choline (PC), phosphatidyl serine (PS), phosphatidyl ethanolamine (PE), and phosphatidyl inositol (PI) vesicles with horse-heart cytochrome C. An interaction could only be detected between cytochrome C and either PS or PI. An apparent equivalence point in the binding was reached for both phospholipids at a molar ratio of phospholipid : protein of 6 : 1. At this point, the reactivity of (eaq-) towards the cytochrome C was very markedly reduced. Indeed, the rate of disappearance of (eaq-) under such conditions was the same as the rate of eaq- disappearance in triply-distilled water. The inclusion of cholesterol at a molar ratio of 1 : 1 within the phospholipid vesicles changed the stoichiometry of the interaction. Evidence that protonated epsilon-amino groups of lysine residues are involved in the interaction is presented. Possible models for the complexes formed are discussed.", "contents": "The interaction of cytochrome C with phospholipids. A pulse-radiolysis study. The reactions of the hydrated electron (eaq-), produced during pulse radiolysis, have been used to study the binding of phosphatidyl choline (PC), phosphatidyl serine (PS), phosphatidyl ethanolamine (PE), and phosphatidyl inositol (PI) vesicles with horse-heart cytochrome C. An interaction could only be detected between cytochrome C and either PS or PI. An apparent equivalence point in the binding was reached for both phospholipids at a molar ratio of phospholipid : protein of 6 : 1. At this point, the reactivity of (eaq-) towards the cytochrome C was very markedly reduced. Indeed, the rate of disappearance of (eaq-) under such conditions was the same as the rate of eaq- disappearance in triply-distilled water. The inclusion of cholesterol at a molar ratio of 1 : 1 within the phospholipid vesicles changed the stoichiometry of the interaction. Evidence that protonated epsilon-amino groups of lysine residues are involved in the interaction is presented. Possible models for the complexes formed are discussed."}
{"id": "PMID:204593", "title": "The influence of protonation or alkylation of the phosphate group on the e.s.r. spectra and on the rate of phosphate elimination from 2-methoxyethyl phosphate 2-yl radicals.", "content": "The e.s.r. spectra of 1-yl, 2-yl and 3'-yl methoxyethyl phosphate radicals derived from CH3OCH2CH2-OPO3H2 by hydrogen abstraction have been measured in aqueous solutions and the hyperfine constants determined. The coupling constants vary strongly with protonation or alkylation of the phosphate group. The 2-yl radicals eliminate phosphate. The rate-constants for the elimination (ke) have been estimated by e.s.r. measurements and by product studies as a function of pH using 60Co gamma-radiolysis. The ke values vary from approximately 0.3 s(-1) for the CH3OCHCH2OPO3--radical and approximately 10(3) s-1 for CH3OCHCH2OPO3H-, to approximately 3 X 10(6) S-1 for CH3OCHCH2OPO3H2. Alkylation of the phosphate group increases the elimination rate-constant to a similar extent as protonation. The results support a recent mechanism which described the OH-radical-induced single-strand breaks of DNA in aqueous solution starting from the C-4' radical of the sugar moiety. It is further concluded the C-4' radical of DNA eliminates the 3'-phosphate group faster than the 5'-phosphate group.", "contents": "The influence of protonation or alkylation of the phosphate group on the e.s.r. spectra and on the rate of phosphate elimination from 2-methoxyethyl phosphate 2-yl radicals. The e.s.r. spectra of 1-yl, 2-yl and 3'-yl methoxyethyl phosphate radicals derived from CH3OCH2CH2-OPO3H2 by hydrogen abstraction have been measured in aqueous solutions and the hyperfine constants determined. The coupling constants vary strongly with protonation or alkylation of the phosphate group. The 2-yl radicals eliminate phosphate. The rate-constants for the elimination (ke) have been estimated by e.s.r. measurements and by product studies as a function of pH using 60Co gamma-radiolysis. The ke values vary from approximately 0.3 s(-1) for the CH3OCHCH2OPO3--radical and approximately 10(3) s-1 for CH3OCHCH2OPO3H-, to approximately 3 X 10(6) S-1 for CH3OCHCH2OPO3H2. Alkylation of the phosphate group increases the elimination rate-constant to a similar extent as protonation. The results support a recent mechanism which described the OH-radical-induced single-strand breaks of DNA in aqueous solution starting from the C-4' radical of the sugar moiety. It is further concluded the C-4' radical of DNA eliminates the 3'-phosphate group faster than the 5'-phosphate group."}
{"id": "PMID:204589", "title": "Battered women: a medical problem requiring detection.", "content": "A one month study of the surgical and psychiatric service of a university hospital emergency room identified thirty-seven women coming for treatment as a result of physical abuse. Thirty-three of the thirty-seven women presented at the surgical services are represented 3.8 per cent of surgical admissions in the emergency room.  These women came from all ages, social and ethnic groups. They usually presented with contusions or other injuries to the head and neck. The majority would not accept psychiatric treatment but were willing to discuss the problem with the emergency room physician if encouraged. The preventive implications of these findings for the nonpsychiatric physician are discussed.", "contents": "Battered women: a medical problem requiring detection. A one month study of the surgical and psychiatric service of a university hospital emergency room identified thirty-seven women coming for treatment as a result of physical abuse. Thirty-three of the thirty-seven women presented at the surgical services are represented 3.8 per cent of surgical admissions in the emergency room.  These women came from all ages, social and ethnic groups. They usually presented with contusions or other injuries to the head and neck. The majority would not accept psychiatric treatment but were willing to discuss the problem with the emergency room physician if encouraged. The preventive implications of these findings for the nonpsychiatric physician are discussed."}
{"id": "PMID:204596", "title": "Invasive primary mucinous carcinoma of the skin.", "content": "An unusual case of primary mucinous carcinoma of the skin has been reported. The tumor progressed very rapidly and recurred twice within a short period after adequate local excision. It had wide spread lymph node metastases and a fatal ending. The characteristic clinical and histologic differentiation from sweat gland carcinoma has been discussed.", "contents": "Invasive primary mucinous carcinoma of the skin. An unusual case of primary mucinous carcinoma of the skin has been reported. The tumor progressed very rapidly and recurred twice within a short period after adequate local excision. It had wide spread lymph node metastases and a fatal ending. The characteristic clinical and histologic differentiation from sweat gland carcinoma has been discussed."}
{"id": "PMID:204599", "title": "Effects of dexamethasone on the morphogenesis of two mutants of Rous sarcoma virus.", "content": "Japanese quail cells transformed by the replication-defective, Bryan high-titer strain of Rous sarcoma virus, BH RSV(-)Q, clone 3, revealed intracytoplasmic A-type particles after dexamethasone treatment. In the absence of dexamethasone, or when superinfected with a helper virus in the presence or absence of dexamethasone, no such particles were observed. Chick embryo cells (CEC) infected with a temperature-sensitive sarcoma virus mutant, LA 334, coordinately defective for transformation and viral replication, showed abnormal accumulation of viral core substances and aberrant budding at the non-permissive temperature (41 degrees). CEC infected with LA 334 and treated with dexamethasone at 41 degrees resulted in more extensive accumulation of abnormal budding without increased release of viral particles. Dexamethasone, however, did not lead to abnormal morphogenesis of virus under permissive conditions. The selective effects of dexamethasone on the morphogenesis of these two mutants of avian sarcoma virus are discussed.", "contents": "Effects of dexamethasone on the morphogenesis of two mutants of Rous sarcoma virus. Japanese quail cells transformed by the replication-defective, Bryan high-titer strain of Rous sarcoma virus, BH RSV(-)Q, clone 3, revealed intracytoplasmic A-type particles after dexamethasone treatment. In the absence of dexamethasone, or when superinfected with a helper virus in the presence or absence of dexamethasone, no such particles were observed. Chick embryo cells (CEC) infected with a temperature-sensitive sarcoma virus mutant, LA 334, coordinately defective for transformation and viral replication, showed abnormal accumulation of viral core substances and aberrant budding at the non-permissive temperature (41 degrees). CEC infected with LA 334 and treated with dexamethasone at 41 degrees resulted in more extensive accumulation of abnormal budding without increased release of viral particles. Dexamethasone, however, did not lead to abnormal morphogenesis of virus under permissive conditions. The selective effects of dexamethasone on the morphogenesis of these two mutants of avian sarcoma virus are discussed."}
{"id": "PMID:204600", "title": "Contrasting characteristics of Marek's disease herpesvirus isolated from chickens with and without avian leukosis virus infection.", "content": "Marek's disease herpesvirus (MDHV) isolated from chickens free of naturally occurring avian leukosis virus (ALV) infection produced characteristic foci in both chicken embryo fibroblast (CEF) and chicken kidney cell (CKC) cultures. MDHV-A, which was extracted from the feather follicle epithelium of chickens naturally infected with ALV, did not induce cytologic changes in CEF cultures, but did cause focus formation in CK cultures. ALV was detected in MDHV-A, but not in MDHV preparations. MDHV-A (reconstructed in vivo) and MDHV were further distinguished from one another by inoculation of ALV-free LSI-SPF chickens. MDHV-A elicited a high incidence of early mortality which was not accompanied by the gross tumor spectrum characteristic of Marek's disease, although extensive histologic lesions were present. The differences between MDHV and MDHV-A were not as striking in another line of ALV-free chickens (SPAFAS). By contrast, among conventional chickens with naturally occurring ALV infection, neither MDHV-A nor MDHV caused appreciable early mortality although both were highly oncogenic (gross tumor development). These observations demonstrate that the presence of an oncornavirus (ALV), detected by radioimmune but not complement fixation assays, can influence the in vitro and in vivo characteristics of an oncogenic herpesvirus (MDHV). The observations recorded here resolve some of the inconsistencies reported in the literature. Thus, the apparent failure by some to find interactions between MDHV and oncornaviruses can be ascribed to the comparatively limited sensitivity of the complement fixation assay used to detect oncornaviruses (ALV). We have shown that the presence of oncornavirus detectable by radioimmune assay, but not by complement fixation, can influence the in vitro and in vivo responses of an oncogenic herpesvirus (MDHV). Our observations relating to viral interaction do not imply that MDHV required the presence of ALV to produce disease.", "contents": "Contrasting characteristics of Marek's disease herpesvirus isolated from chickens with and without avian leukosis virus infection. Marek's disease herpesvirus (MDHV) isolated from chickens free of naturally occurring avian leukosis virus (ALV) infection produced characteristic foci in both chicken embryo fibroblast (CEF) and chicken kidney cell (CKC) cultures. MDHV-A, which was extracted from the feather follicle epithelium of chickens naturally infected with ALV, did not induce cytologic changes in CEF cultures, but did cause focus formation in CK cultures. ALV was detected in MDHV-A, but not in MDHV preparations. MDHV-A (reconstructed in vivo) and MDHV were further distinguished from one another by inoculation of ALV-free LSI-SPF chickens. MDHV-A elicited a high incidence of early mortality which was not accompanied by the gross tumor spectrum characteristic of Marek's disease, although extensive histologic lesions were present. The differences between MDHV and MDHV-A were not as striking in another line of ALV-free chickens (SPAFAS). By contrast, among conventional chickens with naturally occurring ALV infection, neither MDHV-A nor MDHV caused appreciable early mortality although both were highly oncogenic (gross tumor development). These observations demonstrate that the presence of an oncornavirus (ALV), detected by radioimmune but not complement fixation assays, can influence the in vitro and in vivo characteristics of an oncogenic herpesvirus (MDHV). The observations recorded here resolve some of the inconsistencies reported in the literature. Thus, the apparent failure by some to find interactions between MDHV and oncornaviruses can be ascribed to the comparatively limited sensitivity of the complement fixation assay used to detect oncornaviruses (ALV). We have shown that the presence of oncornavirus detectable by radioimmune assay, but not by complement fixation, can influence the in vitro and in vivo responses of an oncogenic herpesvirus (MDHV). Our observations relating to viral interaction do not imply that MDHV required the presence of ALV to produce disease."}
{"id": "PMID:204601", "title": "The polypeptides of hepatitis A virus.", "content": "Hepatitis A virus was purified from fecal specimens obtained from 3 patients with naturally acquired hepatitis A, by a process of differential centrifugation, chloroform extraction, column chromatography, and isopycnic ultracentrifugation. Analysis of purified virus by discontinuous SDS-PAGE revealed three major polypeptides with molecular weights of 34,000, 25,500, and 23,000 daltons. These polypeptides appear to be specific for hepatitis A virus and have similar molecular weights to three of the four major polypeptides reported for members of the genus Enterovirus within the family Picornaviridae.", "contents": "The polypeptides of hepatitis A virus. Hepatitis A virus was purified from fecal specimens obtained from 3 patients with naturally acquired hepatitis A, by a process of differential centrifugation, chloroform extraction, column chromatography, and isopycnic ultracentrifugation. Analysis of purified virus by discontinuous SDS-PAGE revealed three major polypeptides with molecular weights of 34,000, 25,500, and 23,000 daltons. These polypeptides appear to be specific for hepatitis A virus and have similar molecular weights to three of the four major polypeptides reported for members of the genus Enterovirus within the family Picornaviridae."}
{"id": "PMID:204597", "title": "Transabdominal lymphography after intraperitoneal injection of Rous virus in newborn rats.", "content": "Newborn rats were inoculated in the peritoneal cavity with Rous sarcoma virus (Schmidt-Ruppin strain). They were studied lymphographically and histologically after various intervals of time. As a result of lesions of the lymph vessels and nodes, the lymphatic drainage of the peritoneal cavity was increasingly impaired. Pleural effusion developed as a result of leakage through the walls of the lymphatics. The passage through the lymph nodes was blocked and large lymph cysts arose in the mediastinum and retroperitoneally.", "contents": "Transabdominal lymphography after intraperitoneal injection of Rous virus in newborn rats. Newborn rats were inoculated in the peritoneal cavity with Rous sarcoma virus (Schmidt-Ruppin strain). They were studied lymphographically and histologically after various intervals of time. As a result of lesions of the lymph vessels and nodes, the lymphatic drainage of the peritoneal cavity was increasingly impaired. Pleural effusion developed as a result of leakage through the walls of the lymphatics. The passage through the lymph nodes was blocked and large lymph cysts arose in the mediastinum and retroperitoneally."}
{"id": "PMID:204602", "title": "Rapid identification and subtyping of herpes simplex virus by complement-dependent cytotoxicity.", "content": "A simple method for rapid identification and subtyping of herpes simplex virus from clinical specimens is presented. Inoculated cultures demonstrating cytopathic changes were treated with type-specific cytotoxic antisera against herpes simplex virus and complement. Lysis of cells was revealed by staining with trypan blue. The technique allowed identification and subtyping of herpes simplex virus within 2 h after the appearance of CPE.", "contents": "Rapid identification and subtyping of herpes simplex virus by complement-dependent cytotoxicity. A simple method for rapid identification and subtyping of herpes simplex virus from clinical specimens is presented. Inoculated cultures demonstrating cytopathic changes were treated with type-specific cytotoxic antisera against herpes simplex virus and complement. Lysis of cells was revealed by staining with trypan blue. The technique allowed identification and subtyping of herpes simplex virus within 2 h after the appearance of CPE."}
{"id": "PMID:204603", "title": "Observation of togavirus-like particles in nonhuman primates.", "content": "Particles resembling togaviruses were observed by electron microscopy in the urinary bladder lamina propria of one capuchin monkey and in placental syncytiotrophoblasts of one baboon. Type C viruses were observed in the baboon placenta, but not in the tissues of the capuchin monkey.", "contents": "Observation of togavirus-like particles in nonhuman primates. Particles resembling togaviruses were observed by electron microscopy in the urinary bladder lamina propria of one capuchin monkey and in placental syncytiotrophoblasts of one baboon. Type C viruses were observed in the baboon placenta, but not in the tissues of the capuchin monkey."}
{"id": "PMID:204604", "title": "Autoradiographic detection of Epstein-Barr virus (EBV)-associated early antigen in a variety of EBV DNA-containing lymphoblastoid cell lines previously designated as nonproducers.", "content": "By using autoradiography combined with 125I-labeled IgG prepared from human sera containing high anti-EA (early antigen) antibody titers, EA has been detected in a low fraction of cells in a variety of EBV DNA-containing cell lines previously designated as negative for this antigen. These positive cell lines are highly inducible for EA following treatment with iododeoxyuridine (IUDR) and also contain multiple copies of the virus genome on average. The correlation between IUDR inducibility and spontaneous expression of EA, in particular, suggests that the ability to express EA in both situations is interrelated.", "contents": "Autoradiographic detection of Epstein-Barr virus (EBV)-associated early antigen in a variety of EBV DNA-containing lymphoblastoid cell lines previously designated as nonproducers. By using autoradiography combined with 125I-labeled IgG prepared from human sera containing high anti-EA (early antigen) antibody titers, EA has been detected in a low fraction of cells in a variety of EBV DNA-containing cell lines previously designated as negative for this antigen. These positive cell lines are highly inducible for EA following treatment with iododeoxyuridine (IUDR) and also contain multiple copies of the virus genome on average. The correlation between IUDR inducibility and spontaneous expression of EA, in particular, suggests that the ability to express EA in both situations is interrelated."}
{"id": "PMID:204598", "title": "Distributions of 137Cs, 201Tl, 203Hg, 203Pb and 57Co in a rat hepatoma model. Comparison with 67Ga.", "content": "The distribution of carrier-free 203Pb-acetate, 203HgCl2, 57 CoCl2, 137CsCl and 201TlCl was investigated in rats bearing thigh-implanted Morris 7777 hepatomas. Viable and nonviable tumor tissue was collected in order to determine the relative affinities of the radiopharmaceuticals for these tissues. The animals were sacrificed at 4, 24, 48, 72 and 96 hrs following intravenous injection. Washout of the radioisotope from the viable tumor tissue was rapid, the maximum concentration being reached on or before 4 hrs following injection. In contrast, residual activity within the nonviable tumor tissue decreased much more slowly and in some cases even increased with time. Viable tumor-to-muscle and nonviable tumor-to-muscle ratios for 203Pb, 203Hg and 57Co were comparable to the analogous ratios reported for 67Ga. However, none of these isotopes approached 67Ga as a potential tumor imaging agent because the large ratios were the result of low muscle uptake rather than high tumor uptake. Blood clearance of 67Ga was faster than any of the five cations, while viable and nonviable tumor affinity for 67Ga was greater than for any of the radiopharmaceuticals studied.", "contents": "Distributions of 137Cs, 201Tl, 203Hg, 203Pb and 57Co in a rat hepatoma model. Comparison with 67Ga. The distribution of carrier-free 203Pb-acetate, 203HgCl2, 57 CoCl2, 137CsCl and 201TlCl was investigated in rats bearing thigh-implanted Morris 7777 hepatomas. Viable and nonviable tumor tissue was collected in order to determine the relative affinities of the radiopharmaceuticals for these tissues. The animals were sacrificed at 4, 24, 48, 72 and 96 hrs following intravenous injection. Washout of the radioisotope from the viable tumor tissue was rapid, the maximum concentration being reached on or before 4 hrs following injection. In contrast, residual activity within the nonviable tumor tissue decreased much more slowly and in some cases even increased with time. Viable tumor-to-muscle and nonviable tumor-to-muscle ratios for 203Pb, 203Hg and 57Co were comparable to the analogous ratios reported for 67Ga. However, none of these isotopes approached 67Ga as a potential tumor imaging agent because the large ratios were the result of low muscle uptake rather than high tumor uptake. Blood clearance of 67Ga was faster than any of the five cations, while viable and nonviable tumor affinity for 67Ga was greater than for any of the radiopharmaceuticals studied."}
{"id": "PMID:204606", "title": "Relationships between base-exchange in phospholipid metabolism and cyclic-AMP levels of synaptosomal membranes.", "content": "The effect of the base-exchange reaction upon the production of cyclic-AMP at the level of rat brain synaptic membranes has been examined. The exchange with ethanolamine produces a significant decrease of the NaF-stimulated production of the cyclic nucleotide, whereas it increases the noradrenaline-induced production. With some exceptions, the exchange with L-serine produces opposite effects.", "contents": "Relationships between base-exchange in phospholipid metabolism and cyclic-AMP levels of synaptosomal membranes. The effect of the base-exchange reaction upon the production of cyclic-AMP at the level of rat brain synaptic membranes has been examined. The exchange with ethanolamine produces a significant decrease of the NaF-stimulated production of the cyclic nucleotide, whereas it increases the noradrenaline-induced production. With some exceptions, the exchange with L-serine produces opposite effects."}
{"id": "PMID:204607", "title": "Polymeric forms of yeast nicotinamide-adenine dinucleotide-specific isocitrate dehydrogenase in the presence of various ligands.", "content": "The molecular weight of NAD-specific isocitrate dehydrogenase, purified from baker's yeast, has been studied by molecular sieve chromatography. By elution of the enzyme from columns of Sepharose 6B with 0.05 M phosphate buffer, pH 7.6, a mol. wt of 151,000 was measured. Higher values of the mol. wt were measured in presence of the following ligands (mol. wt in parentheses): the substrate, isocitrate (224,000); the activators, citrate (203,000) and AMP (275,000); the inhibitor, NaCl (360,000). A mol. wt of 337,000 was measured when AMP, which antagonizes the inhibition by chloride, was present together with NaCl. The results indicate the absence of a correlation between the aggregation form of the enzyme in presence of the ligands and the effects of these ligands on the enzyme activity.", "contents": "Polymeric forms of yeast nicotinamide-adenine dinucleotide-specific isocitrate dehydrogenase in the presence of various ligands. The molecular weight of NAD-specific isocitrate dehydrogenase, purified from baker's yeast, has been studied by molecular sieve chromatography. By elution of the enzyme from columns of Sepharose 6B with 0.05 M phosphate buffer, pH 7.6, a mol. wt of 151,000 was measured. Higher values of the mol. wt were measured in presence of the following ligands (mol. wt in parentheses): the substrate, isocitrate (224,000); the activators, citrate (203,000) and AMP (275,000); the inhibitor, NaCl (360,000). A mol. wt of 337,000 was measured when AMP, which antagonizes the inhibition by chloride, was present together with NaCl. The results indicate the absence of a correlation between the aggregation form of the enzyme in presence of the ligands and the effects of these ligands on the enzyme activity."}
{"id": "PMID:204611", "title": "Cancer: the eighth plague--a suggestion of pathogenesis.", "content": "The current treatment of cancer is based on the assumption that this disease is the result of autonomous clonal proliferation of aberrant cells which must be excised, irradiated or selectively poisoned to achieve a cure. The presumption that the malignant cell constitutes the disease is now challenged by a variety of clinical observations and experimental studies. Like the grasshopper, which is transformed into a locust under altered environmental conditions, the cancer cell may be the manifestation of a defect in homeostatic regulation of cellular proliferation. Identification of the specific regulatory defect could allow for a more rational and more effective treatment of cancer in man.", "contents": "Cancer: the eighth plague--a suggestion of pathogenesis. The current treatment of cancer is based on the assumption that this disease is the result of autonomous clonal proliferation of aberrant cells which must be excised, irradiated or selectively poisoned to achieve a cure. The presumption that the malignant cell constitutes the disease is now challenged by a variety of clinical observations and experimental studies. Like the grasshopper, which is transformed into a locust under altered environmental conditions, the cancer cell may be the manifestation of a defect in homeostatic regulation of cellular proliferation. Identification of the specific regulatory defect could allow for a more rational and more effective treatment of cancer in man."}
{"id": "PMID:204612", "title": "Effects of prophylactic treatment with the methanol extraction residue fraction of tubercle bacilli (MER) on the development of Rous sarcomas of chickens following challenge with the Rous sarcoma virus.", "content": "Three-month-old chickens were treated with the methanol extraction residue fraction of tubercle bacilli (MER) under different conditions, and subsequently challenged with living Rous sarcoma virus. The birds developed progressively growing sarcomas following viral challenge. A substantial proportion of the hosts which had been pretreated with MER under optimal circumstances (38 to 58%) showed complete and long-lasting regression of the neoplasms, and the survival of many of the animals that did succumb to progressively growing tumors was prolonged. An absolute condition for prophylactic efficacy of MER treatment in this model system was injection of the agent into the same body area (wing) into which subsequent viral challenge was introduced. The quantity of MER employed and the timing of the prophylactic administration were also decisive variables.", "contents": "Effects of prophylactic treatment with the methanol extraction residue fraction of tubercle bacilli (MER) on the development of Rous sarcomas of chickens following challenge with the Rous sarcoma virus. Three-month-old chickens were treated with the methanol extraction residue fraction of tubercle bacilli (MER) under different conditions, and subsequently challenged with living Rous sarcoma virus. The birds developed progressively growing sarcomas following viral challenge. A substantial proportion of the hosts which had been pretreated with MER under optimal circumstances (38 to 58%) showed complete and long-lasting regression of the neoplasms, and the survival of many of the animals that did succumb to progressively growing tumors was prolonged. An absolute condition for prophylactic efficacy of MER treatment in this model system was injection of the agent into the same body area (wing) into which subsequent viral challenge was introduced. The quantity of MER employed and the timing of the prophylactic administration were also decisive variables."}
{"id": "PMID:204608", "title": "Affinity chromatography of yeast nicotinamide-adenine dinucleotide-specific isocitrate dehydrogenase on immobilized nicotinamide-adenine dinucleotide. Effects of ligands.", "content": "The method of affinity chromatography has been used for studying the effects of some ligands of yeast NAD-specific isocitrate dehydrogenase on the affinity of the enzyme for NAD+ immobilized on Sepharose 4B. In absence of ligands, the enzyme is eluted from NAD+-Sepharose columns by 0.1 M phosphate buffer, pH 7.6, in a highly purified form. The elution of enzyme is accelerated by NAD+ and, more effectively, by AMP; and retarded by isocitrate and citrate. The elution patterns show a rather irregular shape, probably due to the occurrence of aggregation processes of the enzyme protein.", "contents": "Affinity chromatography of yeast nicotinamide-adenine dinucleotide-specific isocitrate dehydrogenase on immobilized nicotinamide-adenine dinucleotide. Effects of ligands. The method of affinity chromatography has been used for studying the effects of some ligands of yeast NAD-specific isocitrate dehydrogenase on the affinity of the enzyme for NAD+ immobilized on Sepharose 4B. In absence of ligands, the enzyme is eluted from NAD+-Sepharose columns by 0.1 M phosphate buffer, pH 7.6, in a highly purified form. The elution of enzyme is accelerated by NAD+ and, more effectively, by AMP; and retarded by isocitrate and citrate. The elution patterns show a rather irregular shape, probably due to the occurrence of aggregation processes of the enzyme protein."}
{"id": "PMID:204618", "title": "Inert gas a-A differences: a direct reflection of V/Q distribution.", "content": "A computer model was developed to study the relationship between ventilation-to-perfusion (V/Q) mismatch and the development of inert gas arterial-to-alveolar partial pressure differences (a-A differences). Increasing inhomogeneity of V/Q ratio is revealed directly as an increase in the a-A difference of each gas. The quantitative relationships between the Q vs. V/Q distribution and the fractional a-A difference solubility plot (a-A difference plot) were studied and described. These studies demonstrated that for log normally distributed V/Q ratios, the area under the a-A difference plot is linearly related to the log variance of the V/Q distribution and can be estimated directly from the values obtained from six gases. The maximum a-A difference occurs for a gas whose solubility is numerically equal to the mean V/Q. The effects of departure from log normality and multimodality are discussed. We conclude from these studies that quantitative information regarding the degree of inhomogeneity of V/Q for log normal distribution is available from direct calculations of inert gas retention and excretion data. Qualitative information is also available indicating the departure from log normality and the region toward which the distribution is skewed.", "contents": "Inert gas a-A differences: a direct reflection of V/Q distribution. A computer model was developed to study the relationship between ventilation-to-perfusion (V/Q) mismatch and the development of inert gas arterial-to-alveolar partial pressure differences (a-A differences). Increasing inhomogeneity of V/Q ratio is revealed directly as an increase in the a-A difference of each gas. The quantitative relationships between the Q vs. V/Q distribution and the fractional a-A difference solubility plot (a-A difference plot) were studied and described. These studies demonstrated that for log normally distributed V/Q ratios, the area under the a-A difference plot is linearly related to the log variance of the V/Q distribution and can be estimated directly from the values obtained from six gases. The maximum a-A difference occurs for a gas whose solubility is numerically equal to the mean V/Q. The effects of departure from log normality and multimodality are discussed. We conclude from these studies that quantitative information regarding the degree of inhomogeneity of V/Q for log normal distribution is available from direct calculations of inert gas retention and excretion data. Qualitative information is also available indicating the departure from log normality and the region toward which the distribution is skewed."}
{"id": "PMID:204619", "title": "Longitudinal mixing in pulmonary airways--normal subjects respiring at a constant flow.", "content": "We have measured the impulse response of helium and sulfur hexafluoride in the airways of five normal human subjects at a respiratory flow of 400 ml/s. The longitudinal mixing of the inert gases was characterized by the increased volume variance of the expired concentration response. This parameter was measured over the largest possible range of airway penetrations, 30-290 ml. Employing a symmetrical model of the airway geometry, we have computed the values of a mean mixing coefficient from the volume variance data. This mixing coefficient is largest in the large airways and decreases rapidly with increasing penetration; it may be as much as 4,000 times greater than the molecular diffusivity; and it is relatively independent of the inert gas tested, at least up to an airway penetration of 180 ml. These observations are consistent with several preivously proposed mixing mechanisms including axial streaming, turbulent dispersion, and mixing by geometric asymmetry. However, the latter observation appears to rule out the importance of laminar dispersion since mixing by this mechanism is inversely dependent on the molecular diffusivity.", "contents": "Longitudinal mixing in pulmonary airways--normal subjects respiring at a constant flow. We have measured the impulse response of helium and sulfur hexafluoride in the airways of five normal human subjects at a respiratory flow of 400 ml/s. The longitudinal mixing of the inert gases was characterized by the increased volume variance of the expired concentration response. This parameter was measured over the largest possible range of airway penetrations, 30-290 ml. Employing a symmetrical model of the airway geometry, we have computed the values of a mean mixing coefficient from the volume variance data. This mixing coefficient is largest in the large airways and decreases rapidly with increasing penetration; it may be as much as 4,000 times greater than the molecular diffusivity; and it is relatively independent of the inert gas tested, at least up to an airway penetration of 180 ml. These observations are consistent with several preivously proposed mixing mechanisms including axial streaming, turbulent dispersion, and mixing by geometric asymmetry. However, the latter observation appears to rule out the importance of laminar dispersion since mixing by this mechanism is inversely dependent on the molecular diffusivity."}
{"id": "PMID:204621", "title": "Biochemical activities of the derivatives of dehydrodicaffeic acid dilactone.", "content": "Activities of derivatives of dehydrodicaffeic acid dilactone (DDCAD) to inhibit catechol-O-methyltransferase (COMT), cyclic AMP phosphodiesterase (PDE) and DOPA decarboxylase (DDC) were examined. Among those tested, 2,6-bis-(5',6'-dibromo-4'-hydroxy-3'-methoxyphenyl)-3,7-dioxabicyclo-[3,3,0]-octane 4,8-dione was found to be the strongest inhibitor of both COMT and PDE. There were no derivatives which showed a stronger inhibition against DDC than the original compound, DDCAD.", "contents": "Biochemical activities of the derivatives of dehydrodicaffeic acid dilactone. Activities of derivatives of dehydrodicaffeic acid dilactone (DDCAD) to inhibit catechol-O-methyltransferase (COMT), cyclic AMP phosphodiesterase (PDE) and DOPA decarboxylase (DDC) were examined. Among those tested, 2,6-bis-(5',6'-dibromo-4'-hydroxy-3'-methoxyphenyl)-3,7-dioxabicyclo-[3,3,0]-octane 4,8-dione was found to be the strongest inhibitor of both COMT and PDE. There were no derivatives which showed a stronger inhibition against DDC than the original compound, DDCAD."}
{"id": "PMID:204622", "title": "Hypoglycemia: an overview.", "content": "Hypoglycemia was not described as a human clinical syndrome until exogenous insulin was discovered. Much of our current knowledge of the symptoms of hypoglycemia derived from the reactions of schizophrenics to insulin coma therapy in the late 1920's. The diagnosis of hypoglycemia cannot be made simply on the basis of a blood glucose level since many asymptomatic persons have levels below 50 mg/100 ml. The diagnosis should be made only if symptoms occur at the glucose nadir and are relieved by the administration of glucose. The most common organic cause of hypoglycemia is functioning islet-cell tumor. By far the most prevalent type of hypoglycemia is idiopathic (function), a condition whose pathophysiology is not understood and which has given rise to a popular lay \"mythology.\"", "contents": "Hypoglycemia: an overview. Hypoglycemia was not described as a human clinical syndrome until exogenous insulin was discovered. Much of our current knowledge of the symptoms of hypoglycemia derived from the reactions of schizophrenics to insulin coma therapy in the late 1920's. The diagnosis of hypoglycemia cannot be made simply on the basis of a blood glucose level since many asymptomatic persons have levels below 50 mg/100 ml. The diagnosis should be made only if symptoms occur at the glucose nadir and are relieved by the administration of glucose. The most common organic cause of hypoglycemia is functioning islet-cell tumor. By far the most prevalent type of hypoglycemia is idiopathic (function), a condition whose pathophysiology is not understood and which has given rise to a popular lay \"mythology.\""}
{"id": "PMID:204623", "title": "Hysterical symptoms masking brain stem glioma.", "content": "To function effectively as primary care specialists, psychiatrists must remain ever alert to the possibility of organic disorders in patients who at first show only psychiatric symptoms. A case is presented in which hysterical overlay led to misdiagnosis in a 31 year woman, who dies of a diffuse medullary glioma 3 1/2 years after onset of \"conversion\" symptoms. The authors point out how the label \"hysterical\" clouds longitudinal objective diagnostic observations especially when initial clinical and laboratory data fail to support a definitive organic diagnosis.", "contents": "Hysterical symptoms masking brain stem glioma. To function effectively as primary care specialists, psychiatrists must remain ever alert to the possibility of organic disorders in patients who at first show only psychiatric symptoms. A case is presented in which hysterical overlay led to misdiagnosis in a 31 year woman, who dies of a diffuse medullary glioma 3 1/2 years after onset of \"conversion\" symptoms. The authors point out how the label \"hysterical\" clouds longitudinal objective diagnostic observations especially when initial clinical and laboratory data fail to support a definitive organic diagnosis."}
{"id": "PMID:204624", "title": "Clinic versus private treatment of psychosis.", "content": "Thirty patients with a hospital diagnosis of schizophrenia were randomly assigned upon discharge to either 1) a specialized aftercare clinic of 2) to private psychiatrists. At the end of six months, the clinic patients had spent significantly less time as hospital readmissions and were significantly more occupied (i.e. employed or in school) than the private patients. It seems possible that attendance at clinic provides group pressure to maintain drug compliance and may thus work to reduce rehospitalization. It is also likely that the network of clinic paramedical and volunteer staff, by its flexibility and availability, aids the patient's transition into employment.", "contents": "Clinic versus private treatment of psychosis. Thirty patients with a hospital diagnosis of schizophrenia were randomly assigned upon discharge to either 1) a specialized aftercare clinic of 2) to private psychiatrists. At the end of six months, the clinic patients had spent significantly less time as hospital readmissions and were significantly more occupied (i.e. employed or in school) than the private patients. It seems possible that attendance at clinic provides group pressure to maintain drug compliance and may thus work to reduce rehospitalization. It is also likely that the network of clinic paramedical and volunteer staff, by its flexibility and availability, aids the patient's transition into employment."}
{"id": "PMID:204625", "title": "Antibody and cell-mediated immunity to herpes simplex virus in psychotic depression.", "content": "The incidence and antibody titers to herpes simplex virus (HSV) were found significantly higher in patients with psychotic depression as compared to normal controls. Furthermore, the cell-mediated immunity (CMI) to HSV in psychotic depression was similar to that observed after acute HSV infection or recurrence. The results suggest therefore an association between HSV infection and psychotic depression.", "contents": "Antibody and cell-mediated immunity to herpes simplex virus in psychotic depression. The incidence and antibody titers to herpes simplex virus (HSV) were found significantly higher in patients with psychotic depression as compared to normal controls. Furthermore, the cell-mediated immunity (CMI) to HSV in psychotic depression was similar to that observed after acute HSV infection or recurrence. The results suggest therefore an association between HSV infection and psychotic depression."}
{"id": "PMID:204626", "title": "Micro determination of unsaturated disaccharide formed by the action of acidic glycosaminoglycan-endoeliminases. An application of the thiobarbituric acid method to the assay of D-gluco-4-enepyranosyluronic acid-containing disaccharides.", "content": "An improved method is described for the micro determination of acidic glycosaminoglycans after digestion with chondroitinase-ABC and -AC. The determination is based on the color production of D-gluco-4-enepyranosyluronic acid-containing disaccharides produced by the action of chondroitinase-ABC and -AC (acidic glycosaminoglycans-endoeliminase) when the periodate-thiobarbituric acid method is applied to the alpha,beta-unsaturated disaccharides. Suitable conditions for the quantitative assay are described.", "contents": "Micro determination of unsaturated disaccharide formed by the action of acidic glycosaminoglycan-endoeliminases. An application of the thiobarbituric acid method to the assay of D-gluco-4-enepyranosyluronic acid-containing disaccharides. An improved method is described for the micro determination of acidic glycosaminoglycans after digestion with chondroitinase-ABC and -AC. The determination is based on the color production of D-gluco-4-enepyranosyluronic acid-containing disaccharides produced by the action of chondroitinase-ABC and -AC (acidic glycosaminoglycans-endoeliminase) when the periodate-thiobarbituric acid method is applied to the alpha,beta-unsaturated disaccharides. Suitable conditions for the quantitative assay are described."}
{"id": "PMID:204627", "title": "C-type cytochromes isloated from an extreme thermophile, Thermus thermophilus HB8.", "content": "Two cytochromes of the C-type, c-554 and c-549, were isolated from the soluble fraction of an extreme thermophile, Thermus thermophilus HB8. Highly purified cytochrome c-554 had absorption maxima at 554, 522, and 417 nm in the reduced state, and at 410 nm in the oxidized state. The alpha-band of the reduced state resembled that of \"split-alpha\" cytochromes. The isoelectric point was at pH 4.9, and the molecular weight was about 29,000. Cytochrome c-549, partially purified, had absorption maxima a6 549,520, and 416 nm in the reduced form, and at 408 nm in the oxidized form. The molecular weight was about 25,000. Both were slowly auto-oxidizable, and did not combine with CO.", "contents": "C-type cytochromes isloated from an extreme thermophile, Thermus thermophilus HB8. Two cytochromes of the C-type, c-554 and c-549, were isolated from the soluble fraction of an extreme thermophile, Thermus thermophilus HB8. Highly purified cytochrome c-554 had absorption maxima at 554, 522, and 417 nm in the reduced state, and at 410 nm in the oxidized state. The alpha-band of the reduced state resembled that of \"split-alpha\" cytochromes. The isoelectric point was at pH 4.9, and the molecular weight was about 29,000. Cytochrome c-549, partially purified, had absorption maxima a6 549,520, and 416 nm in the reduced form, and at 408 nm in the oxidized form. The molecular weight was about 25,000. Both were slowly auto-oxidizable, and did not combine with CO."}
{"id": "PMID:204628", "title": "A single cleavage of Simian virus 40 (SV40) DNA by a site specific endonuclease from Thermus aquaticus, Taq I.", "content": "A site specific endonuclease from Thermus aquaticus, Taq I, cleaves Simian virus 40 (SV40) DNA at a single site. The cleavage site was localized on the physical map by double digestions, using the previously characterized fragments produced by digestion with Hae II, Hae III, AluI, HhaI, HinfI, or BstI. The Taq I site is located at the position that is 56.5% of the unit length from the Eco RI site.", "contents": "A single cleavage of Simian virus 40 (SV40) DNA by a site specific endonuclease from Thermus aquaticus, Taq I. A site specific endonuclease from Thermus aquaticus, Taq I, cleaves Simian virus 40 (SV40) DNA at a single site. The cleavage site was localized on the physical map by double digestions, using the previously characterized fragments produced by digestion with Hae II, Hae III, AluI, HhaI, HinfI, or BstI. The Taq I site is located at the position that is 56.5% of the unit length from the Eco RI site."}
{"id": "PMID:204629", "title": "Presence of the sites for interacting with cyclic AMP and with catalytic subunit on small fragments of protein kinase regulatory subunit.", "content": "During the purification of cyclic AMP binding proteins from rat liver, some smaller active fragments were obtained, possibly as the result of proteolysis. The binding proteins detected had approximate molecular weights of 50,000, 36,000, and 10,000. Each of these components bound cyclic [3H]AMP with high affinity (apparent dissociation constants ranging from 2 to 10 nM) and had a similar ability to inhibit the purified catalytic subunit of rat liver protein kinase. Cyclic AMP prevented this inhibition in each instance. These results suggest that the binding site for cyclic AMP and the site for interacting with catalytic subunit occur relatively close to one another on the regulatory subunit and can remain functional when a substantial fraction of the subunit is lost.", "contents": "Presence of the sites for interacting with cyclic AMP and with catalytic subunit on small fragments of protein kinase regulatory subunit. During the purification of cyclic AMP binding proteins from rat liver, some smaller active fragments were obtained, possibly as the result of proteolysis. The binding proteins detected had approximate molecular weights of 50,000, 36,000, and 10,000. Each of these components bound cyclic [3H]AMP with high affinity (apparent dissociation constants ranging from 2 to 10 nM) and had a similar ability to inhibit the purified catalytic subunit of rat liver protein kinase. Cyclic AMP prevented this inhibition in each instance. These results suggest that the binding site for cyclic AMP and the site for interacting with catalytic subunit occur relatively close to one another on the regulatory subunit and can remain functional when a substantial fraction of the subunit is lost."}
{"id": "PMID:204630", "title": "Phosphoglycolate phosphatase. Purification and properties.", "content": "Phosphoglycolate phosphatase (EC 3.1.3.18) was purified 1500-fold from field-grown tobacco leaves by acetone fractionation, DEAE-cellulose and molecular sieve chromatography, and preparative polyacrylamide gel electrophoresis. Preparations were judged 90 to 95% homogeneous by chromatography on DEAE-cellulose, polyacrylamide gel electrophoresis, and by isoelectric focusing. The highest specific activity obtained was 468 mumol of phosphate released/min/mg of protein. The native protein has a molecular weight of 80,500 by Ferguson plot analysis and 86,300 by sedimentation velocity on sucrose density gradients. Sodium dodecyl sulfate-polyacrylamide gels gave a molecular weight of 20,700, indicating the P-glycolate phosphatase is a tetramer with identical or near identical subunits. The enzyme, freshly purified or in crude homogenates, had a pI of 3.8 to 3.9 pH units by isoelectric focusing. Phosphosphoglycolate phosphatase from spinach leaves has a molecular weight of 93,000 and, unlike the enzyme from tobacco leaves, it is extremely unstable after DEAE-cellulose chromatography and is inactivated by lipase (EC 3.1.1.3). The phosphatase from both plants was stabilized by the addition of citrate or isocitrate in the buffers. Ribose 5-phosphate is a competitive inhibitor of phosphoglycolate phosphatase at physiological concentration, while other phosphate esters of the photosynthetic carbon cycle were without effect.", "contents": "Phosphoglycolate phosphatase. Purification and properties. Phosphoglycolate phosphatase (EC 3.1.3.18) was purified 1500-fold from field-grown tobacco leaves by acetone fractionation, DEAE-cellulose and molecular sieve chromatography, and preparative polyacrylamide gel electrophoresis. Preparations were judged 90 to 95% homogeneous by chromatography on DEAE-cellulose, polyacrylamide gel electrophoresis, and by isoelectric focusing. The highest specific activity obtained was 468 mumol of phosphate released/min/mg of protein. The native protein has a molecular weight of 80,500 by Ferguson plot analysis and 86,300 by sedimentation velocity on sucrose density gradients. Sodium dodecyl sulfate-polyacrylamide gels gave a molecular weight of 20,700, indicating the P-glycolate phosphatase is a tetramer with identical or near identical subunits. The enzyme, freshly purified or in crude homogenates, had a pI of 3.8 to 3.9 pH units by isoelectric focusing. Phosphosphoglycolate phosphatase from spinach leaves has a molecular weight of 93,000 and, unlike the enzyme from tobacco leaves, it is extremely unstable after DEAE-cellulose chromatography and is inactivated by lipase (EC 3.1.1.3). The phosphatase from both plants was stabilized by the addition of citrate or isocitrate in the buffers. Ribose 5-phosphate is a competitive inhibitor of phosphoglycolate phosphatase at physiological concentration, while other phosphate esters of the photosynthetic carbon cycle were without effect."}
{"id": "PMID:204631", "title": "Mechanism of phosphoglycolate phosphatase. Studies of hydrolysis and transphosphorylation, substrate analogs, and sulfhydryl inhibition.", "content": "Enzymatic hydrolysis of phosphoglycolate proceeds through O-P bond cleavage as determined by reaction in H218O and analysis of the trimethylsilyl derivatives of the reaction products by mass spectrometry. No phosphate, hydroxyl, or carboxyl exchange occurred. End product inhibition was consistent with an ordered release of products, first the alcoholic product, glycolate, then phosphate. Analysis of the data indicated that the phosphate.enzyme complex dissociated very rapidly, and this was confirmed by use of alternative phosphomonoester substrates. Maximum velocity with these alternate substrates was found to be proportional to the pKa of of the corresponding alcoholic product, indicating the rate-limiting step in the reaction was protonation of the bridge oxygen. The use of substrate analogs further suggested that enzymatic specificity residues in exacting steric requirements for binding, and that large alkyl groups were excluded on this basis. Phosphoglycolate phosphatase catalyzed transphorylation to a wide range of acceptors and was inhibited at the active site by diisopropyl-fluorophosphate. The data suggest that the reaction sequence proceeds via a phosphoenzyme intermediate. N-Ethylmaleimide slowly inactivated the enzyme, the rate being greatly increased by P-glycolate, but not by magnesium or phosphate ions. The data suggest a conformational change is necessary to induce the transition state complex and phosphoenzyme formation. This may account for the phosphate acceptor specificity and is consistent with the failure to observe an enzyme-mediated H2O-phosphate oxygen exchange.", "contents": "Mechanism of phosphoglycolate phosphatase. Studies of hydrolysis and transphosphorylation, substrate analogs, and sulfhydryl inhibition. Enzymatic hydrolysis of phosphoglycolate proceeds through O-P bond cleavage as determined by reaction in H218O and analysis of the trimethylsilyl derivatives of the reaction products by mass spectrometry. No phosphate, hydroxyl, or carboxyl exchange occurred. End product inhibition was consistent with an ordered release of products, first the alcoholic product, glycolate, then phosphate. Analysis of the data indicated that the phosphate.enzyme complex dissociated very rapidly, and this was confirmed by use of alternative phosphomonoester substrates. Maximum velocity with these alternate substrates was found to be proportional to the pKa of of the corresponding alcoholic product, indicating the rate-limiting step in the reaction was protonation of the bridge oxygen. The use of substrate analogs further suggested that enzymatic specificity residues in exacting steric requirements for binding, and that large alkyl groups were excluded on this basis. Phosphoglycolate phosphatase catalyzed transphorylation to a wide range of acceptors and was inhibited at the active site by diisopropyl-fluorophosphate. The data suggest that the reaction sequence proceeds via a phosphoenzyme intermediate. N-Ethylmaleimide slowly inactivated the enzyme, the rate being greatly increased by P-glycolate, but not by magnesium or phosphate ions. The data suggest a conformational change is necessary to induce the transition state complex and phosphoenzyme formation. This may account for the phosphate acceptor specificity and is consistent with the failure to observe an enzyme-mediated H2O-phosphate oxygen exchange."}
{"id": "PMID:204634", "title": "Interaction of cytochrome c with cytochrome c oxidase. Photoaffinity labeling of beef heart cytochrome c oxidase with arylazido-cytochrome c.", "content": "Cytochrome c derivatives labeled with a 3-nitrophenylazido group at lysine 13, at lysine 22, or at both residues have been prepared. The interaction of the cytochrome c derivatives with beef heart cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) in the presence of ultrviolet light results in formation of a covalent complex between cytochrome c and the oxidase. Using the lysine 22 derivative, the polypeptide composition of the oxidase is not modified, nor is its catalytic activity, whereas with the lysine 13 derivative, the gel electrophoretic pattern is altered and the catalytic activity of the complex diminished. The data are consisten with a specfic covalent interaction of the lysine 13 derivative of cytochrome c with the polypeptide of molecular weight 23,700 (Subunit II) of cytochrome c oxidase.", "contents": "Interaction of cytochrome c with cytochrome c oxidase. Photoaffinity labeling of beef heart cytochrome c oxidase with arylazido-cytochrome c. Cytochrome c derivatives labeled with a 3-nitrophenylazido group at lysine 13, at lysine 22, or at both residues have been prepared. The interaction of the cytochrome c derivatives with beef heart cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) in the presence of ultrviolet light results in formation of a covalent complex between cytochrome c and the oxidase. Using the lysine 22 derivative, the polypeptide composition of the oxidase is not modified, nor is its catalytic activity, whereas with the lysine 13 derivative, the gel electrophoretic pattern is altered and the catalytic activity of the complex diminished. The data are consisten with a specfic covalent interaction of the lysine 13 derivative of cytochrome c with the polypeptide of molecular weight 23,700 (Subunit II) of cytochrome c oxidase."}
{"id": "PMID:204635", "title": "Cyclic nucleotide phosphodiesterase. Partial purification and characterization of a high affinity enzyme activity from human lung tissue.", "content": "Part of the soluble cyclic nucleotide phosphodiesterase activity of crude human lung tissue can be attributed to a thermosensitive (37 degrees) enzyme with a high apparent affinity for both adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP). The enzyme can be partially purified by DEAE-Sephadex chromatography. In the presence of 0.1 mM EDTA or ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid (EGTA), it is eluted from the column immediately before a cyclic GMP-specific phosphodiesterase, but in the presence of 0.2 mM Ca2+, the elution follows that of the cyclic GMP-specific enzyme. The two forms of the nonspecific phosphodiesterase activity are referred to as DEAD-Sephadex Fractions Ia and Ic, respectively. Their apparent molecular weights, recorded at gel filtration, vary with different preparations from 230,000 to 150,000. Occasionally, corresponding recordings for main peaks of activity also cluster round the values 120,000, 105,000, and 78,000. The enzymatic properties of Fractions Ia and Ic closely resemble each other. The enzyme activity is blocked by EDTA, partially inhibited in the presence of 1,10-phenanthroline, but only slightly affected by EGTA. The inhibitory effect of EDTA can be overcome by Mg2+ and Mn2+ and that of 1,10-phenanthroline, in part, by Zn2+; this cation in itself is inhibitory at millimolar concentrations. With submicromolar substrate concentrations, the activity of either fraction obeys linear kinetics displaying an apparent Km of approximately 0.4 micron for both substrates. Reciprocal inhibition experiments suggest that hydrolysis of both cyclic AMP and cyclic GMP is performed by the same active site. Examination of the activity using extended substrate concentration ranges indicates nonlinear kinetics; Hill plots of such data also show nonlinear curvature. The activity is inhibited by micromolar concentrations of inosine 3':5'-monophosphate (cyclic IMP), 3-isobutyl-1-methylxanthine, papervine, and some antiallergic agents. Theophylline and disodium cromoglycate are less potent inhibitors. Inhibition of activity by Lubrol PX follows a biphasic dose response curve. The activity of Fraction Ia can be enhanced 2- to 3-fold by a Ca2+-dependent activator prepared from lung tissue, whose action is counteracted by chlorpromazine, and by lysophosphatidylcholine. It is initially enhanced but subsequently decreased at exposure to trypsin. Fraction Ic is less prone to activation by these agents. The results indicate that the present activity represents an enzyme form that differs from three previously described phosphodiesterases of human lung tissue. It is apparently related to, but also shows distinct differences from the Ca2+-dependent enzyme(s) of brain and heart tissue.", "contents": "Cyclic nucleotide phosphodiesterase. Partial purification and characterization of a high affinity enzyme activity from human lung tissue. Part of the soluble cyclic nucleotide phosphodiesterase activity of crude human lung tissue can be attributed to a thermosensitive (37 degrees) enzyme with a high apparent affinity for both adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP). The enzyme can be partially purified by DEAE-Sephadex chromatography. In the presence of 0.1 mM EDTA or ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid (EGTA), it is eluted from the column immediately before a cyclic GMP-specific phosphodiesterase, but in the presence of 0.2 mM Ca2+, the elution follows that of the cyclic GMP-specific enzyme. The two forms of the nonspecific phosphodiesterase activity are referred to as DEAD-Sephadex Fractions Ia and Ic, respectively. Their apparent molecular weights, recorded at gel filtration, vary with different preparations from 230,000 to 150,000. Occasionally, corresponding recordings for main peaks of activity also cluster round the values 120,000, 105,000, and 78,000. The enzymatic properties of Fractions Ia and Ic closely resemble each other. The enzyme activity is blocked by EDTA, partially inhibited in the presence of 1,10-phenanthroline, but only slightly affected by EGTA. The inhibitory effect of EDTA can be overcome by Mg2+ and Mn2+ and that of 1,10-phenanthroline, in part, by Zn2+; this cation in itself is inhibitory at millimolar concentrations. With submicromolar substrate concentrations, the activity of either fraction obeys linear kinetics displaying an apparent Km of approximately 0.4 micron for both substrates. Reciprocal inhibition experiments suggest that hydrolysis of both cyclic AMP and cyclic GMP is performed by the same active site. Examination of the activity using extended substrate concentration ranges indicates nonlinear kinetics; Hill plots of such data also show nonlinear curvature. The activity is inhibited by micromolar concentrations of inosine 3':5'-monophosphate (cyclic IMP), 3-isobutyl-1-methylxanthine, papervine, and some antiallergic agents. Theophylline and disodium cromoglycate are less potent inhibitors. Inhibition of activity by Lubrol PX follows a biphasic dose response curve. The activity of Fraction Ia can be enhanced 2- to 3-fold by a Ca2+-dependent activator prepared from lung tissue, whose action is counteracted by chlorpromazine, and by lysophosphatidylcholine. It is initially enhanced but subsequently decreased at exposure to trypsin. Fraction Ic is less prone to activation by these agents. The results indicate that the present activity represents an enzyme form that differs from three previously described phosphodiesterases of human lung tissue. It is apparently related to, but also shows distinct differences from the Ca2+-dependent enzyme(s) of brain and heart tissue."}
{"id": "PMID:204637", "title": "The purine nucleotide cycle. Studies of ammonia production and interconversions of adenine and hypoxanthine nucleotides and nucleosides by rat brain in situ.", "content": "Electrical shock treatment produces a rapid loss of high energy phosphates in rat brain. The [ATP]/[ADP] ratio decreases to one-third of its control value within 10 s. The ammonia content increases 3-fold during the first minute after starting the stimulus. The total adenine nucleotide plus adenosine content of brain decreases an equivalent amount of hypoxanthine-containing compounds appears. Adenosine, inosine, and hypoxanthine accumulate, and there is a transitory accumulation of adenylosuccinate. The contents of ATP and creatine phosphate, and the [ATP]/[ADP] ratio, are rapidly restored to control values, but other metabolite contents are restored more slowly. The transient rise in adenylosuccinate and IMP provides evidence that the ammonia production is due in part, and possibly in whole, to the operation of the purine nucleotide cycle.", "contents": "The purine nucleotide cycle. Studies of ammonia production and interconversions of adenine and hypoxanthine nucleotides and nucleosides by rat brain in situ. Electrical shock treatment produces a rapid loss of high energy phosphates in rat brain. The [ATP]/[ADP] ratio decreases to one-third of its control value within 10 s. The ammonia content increases 3-fold during the first minute after starting the stimulus. The total adenine nucleotide plus adenosine content of brain decreases an equivalent amount of hypoxanthine-containing compounds appears. Adenosine, inosine, and hypoxanthine accumulate, and there is a transitory accumulation of adenylosuccinate. The contents of ATP and creatine phosphate, and the [ATP]/[ADP] ratio, are rapidly restored to control values, but other metabolite contents are restored more slowly. The transient rise in adenylosuccinate and IMP provides evidence that the ammonia production is due in part, and possibly in whole, to the operation of the purine nucleotide cycle."}
{"id": "PMID:204638", "title": "Similarities in the membrane fluidity of 3T3 and SV101-3T3 cells and its relation to concanavalin A- and wheat germ agglutinin-induced agglutination.", "content": "Intact, viable ultransformed 3T3 and transformed SV101-3T3 cells were labeled with fatty acid spin labels and with 2,2,6,6-tetramethylpiperidine-1-oxyl in order to measure the fluidity properties of membrane lipids. Both cell types were grown in regular calf serum and in a lipid-depleted serum supplemented with either oleate or elaidate. The temperature dependence of the spectra obtained revealed inflections that correlate with the temperature below which agglutination with concanavalin A is inhibited, and another inflection that correlates with the temperature below which agglutination with wheat germ agglutinin is inhibited, suggesting that (a) the lipid phase(s) in the vicinity of the receptor(s) for these two lectins differ, and (b) a fluid membrane in the vicinity of the lectin receptor(s) is necessary for agglutination with either concanavalin A or wheat germ agglutinin. Studies with a partially characterized plasma membrane fraction suggest that the plasma membrane fluidity parameters closely resemble those of the intact cell. 3T3 and SV101-3T3 cells show virtually identical fluidity profiles by all of the tests we have applied.", "contents": "Similarities in the membrane fluidity of 3T3 and SV101-3T3 cells and its relation to concanavalin A- and wheat germ agglutinin-induced agglutination. Intact, viable ultransformed 3T3 and transformed SV101-3T3 cells were labeled with fatty acid spin labels and with 2,2,6,6-tetramethylpiperidine-1-oxyl in order to measure the fluidity properties of membrane lipids. Both cell types were grown in regular calf serum and in a lipid-depleted serum supplemented with either oleate or elaidate. The temperature dependence of the spectra obtained revealed inflections that correlate with the temperature below which agglutination with concanavalin A is inhibited, and another inflection that correlates with the temperature below which agglutination with wheat germ agglutinin is inhibited, suggesting that (a) the lipid phase(s) in the vicinity of the receptor(s) for these two lectins differ, and (b) a fluid membrane in the vicinity of the lectin receptor(s) is necessary for agglutination with either concanavalin A or wheat germ agglutinin. Studies with a partially characterized plasma membrane fraction suggest that the plasma membrane fluidity parameters closely resemble those of the intact cell. 3T3 and SV101-3T3 cells show virtually identical fluidity profiles by all of the tests we have applied."}
{"id": "PMID:204639", "title": "DNA-directed in vitro synthesis of Escherichia coli beta-isopropylmalate dehydrogenase.", "content": "The in vitro synthesis of beta-isopropylmalate dehydrogenase (EC 1.1.1.85), an enzyme involved in leucine biosynthesis, has been obtained using as template DNA from the hybrid plasmid (pLC1) which contains the Escherichia coli leucine operon. Enzyme synthesis in vitro is stimulated about 2-fold by guanosine-5'-diphosphate-3'-diphosphate and inhibited about 60% by 2 X 10(-4) M L-leucine.", "contents": "DNA-directed in vitro synthesis of Escherichia coli beta-isopropylmalate dehydrogenase. The in vitro synthesis of beta-isopropylmalate dehydrogenase (EC 1.1.1.85), an enzyme involved in leucine biosynthesis, has been obtained using as template DNA from the hybrid plasmid (pLC1) which contains the Escherichia coli leucine operon. Enzyme synthesis in vitro is stimulated about 2-fold by guanosine-5'-diphosphate-3'-diphosphate and inhibited about 60% by 2 X 10(-4) M L-leucine."}
{"id": "PMID:204640", "title": "Active phosphate ion transport in plasma membrane vesicles isolated from mouse fibroblasts.", "content": "Inorganic phosphate accumulated 8-fold in plasma membrane vesicles derived from simian virus 40-transformed 3T3 mouse fibroblasts when a NaCl gradient (external greater than internal) was artificially imposed across the membrane. Preincubation with Na+ or addition of monensin markedly reduced phosphate accumulation. Na+-stimulated phosphate transport was not affected by addition of either dicarboxylic acids, antimycin A, or ouabain and persisted after addition of proton ionophores. The coupling of phosphate transport to Na+ gradients was pH-dependent, with maximal stimulation by Na+ below pH 7. These findings suggest that monovalent phosphate anion moves across the plasma membrane in co-transport with sodium ion.", "contents": "Active phosphate ion transport in plasma membrane vesicles isolated from mouse fibroblasts. Inorganic phosphate accumulated 8-fold in plasma membrane vesicles derived from simian virus 40-transformed 3T3 mouse fibroblasts when a NaCl gradient (external greater than internal) was artificially imposed across the membrane. Preincubation with Na+ or addition of monensin markedly reduced phosphate accumulation. Na+-stimulated phosphate transport was not affected by addition of either dicarboxylic acids, antimycin A, or ouabain and persisted after addition of proton ionophores. The coupling of phosphate transport to Na+ gradients was pH-dependent, with maximal stimulation by Na+ below pH 7. These findings suggest that monovalent phosphate anion moves across the plasma membrane in co-transport with sodium ion."}
{"id": "PMID:204643", "title": "Aspartokinase I-homoserine dehydrogenase I of Escherichia coli K12. Concentration-dependent dissociation to dimers in the presence of L-threonine.", "content": "The concentration-dependent association-dissociation equilibrium of the bifunctional enzyme aspartokinase I-homoserine dehydrogenase I of Escherichia coli K12 has been investigated at pH 7.6 in the presence of 10 mM L-threonine and 0.1 M KCl by equilibrium gel permeation monitored by a single-photon counting spectrophotometer. The results obtained are consistent with the existence of a dimer-tetramer equilibrium with the association constant of 2.6 X 10(7) M-1 (deltaG0 = -9.9 kcal/mol of dimer). The limiting partition cross-sections estimated by a three-parameter least squares minimization procedure indicate that the molecular radii of the dimer and tetramer are 53.8 A and 70 A, respectively. Both the dimeric and tetrameric forms of the enzyme possess dehydrogenase activity. Treatment of the enzyme with the chaotropic salts, potassium thiocyanate or potassium trichloroacetate, generates a monomeric form that is devoid of dehydrogenase activity. The catalytically inactive monomeric form of the enzyme has a molecular radius between 43 and 45.5 A and a molecular weight of approximately 80,000 as determined by small zone gel chromatography and sedimentation equilibrium studies.", "contents": "Aspartokinase I-homoserine dehydrogenase I of Escherichia coli K12. Concentration-dependent dissociation to dimers in the presence of L-threonine. The concentration-dependent association-dissociation equilibrium of the bifunctional enzyme aspartokinase I-homoserine dehydrogenase I of Escherichia coli K12 has been investigated at pH 7.6 in the presence of 10 mM L-threonine and 0.1 M KCl by equilibrium gel permeation monitored by a single-photon counting spectrophotometer. The results obtained are consistent with the existence of a dimer-tetramer equilibrium with the association constant of 2.6 X 10(7) M-1 (deltaG0 = -9.9 kcal/mol of dimer). The limiting partition cross-sections estimated by a three-parameter least squares minimization procedure indicate that the molecular radii of the dimer and tetramer are 53.8 A and 70 A, respectively. Both the dimeric and tetrameric forms of the enzyme possess dehydrogenase activity. Treatment of the enzyme with the chaotropic salts, potassium thiocyanate or potassium trichloroacetate, generates a monomeric form that is devoid of dehydrogenase activity. The catalytically inactive monomeric form of the enzyme has a molecular radius between 43 and 45.5 A and a molecular weight of approximately 80,000 as determined by small zone gel chromatography and sedimentation equilibrium studies."}
{"id": "PMID:204648", "title": "The preparation and characterization of highly purified, enzymically active complex III from baker's yeast.", "content": "A soluble enzymically active cytochrome b.c1 complex has been purified from baker's yeast mitochondria by a procedure involving solubilization in cholate, differential fractionation with ammonium sulfate, and ultracentrifugation. The resulting particle is free of both cytochrome c oxidase and succinate dehydrogenase activities. The complex contains cytochromes b and c1 in a ratio of 2:1 and quinone and iron-sulfur protein in amounts roughly stoichiometric with cytochrome c1. EPR spectroscopy has shown the iron-sulfur protein to be present mainly as the Rieske protein. EPR spectroscopy also shows a heterogeneity in the cytochrome b population with resonances appearing at g = 3.60 (cytochrome bK) and g = 3.76 (cytochrome bT). A third EPR resonance appearing in the region associated with low spin ferric hemes (g = 3.49) is assigned to cytochrome c1. Anaerobic titration of the complex with dithionite confirmed the heterogeneity in the cytochrome b population and demonstrated that the oxidation-reduction potential of the iron-sulfur protein is approximately 30 mV more positive than cytochrome c1. An intense EPR signal assigned to the coenzyme Q free radical appeared midway in the reductive titration; this signal disappeared toward the end of the titration. A conformational change in the iron-sulfur protein attendant on reduction of a low potential species was noted.", "contents": "The preparation and characterization of highly purified, enzymically active complex III from baker's yeast. A soluble enzymically active cytochrome b.c1 complex has been purified from baker's yeast mitochondria by a procedure involving solubilization in cholate, differential fractionation with ammonium sulfate, and ultracentrifugation. The resulting particle is free of both cytochrome c oxidase and succinate dehydrogenase activities. The complex contains cytochromes b and c1 in a ratio of 2:1 and quinone and iron-sulfur protein in amounts roughly stoichiometric with cytochrome c1. EPR spectroscopy has shown the iron-sulfur protein to be present mainly as the Rieske protein. EPR spectroscopy also shows a heterogeneity in the cytochrome b population with resonances appearing at g = 3.60 (cytochrome bK) and g = 3.76 (cytochrome bT). A third EPR resonance appearing in the region associated with low spin ferric hemes (g = 3.49) is assigned to cytochrome c1. Anaerobic titration of the complex with dithionite confirmed the heterogeneity in the cytochrome b population and demonstrated that the oxidation-reduction potential of the iron-sulfur protein is approximately 30 mV more positive than cytochrome c1. An intense EPR signal assigned to the coenzyme Q free radical appeared midway in the reductive titration; this signal disappeared toward the end of the titration. A conformational change in the iron-sulfur protein attendant on reduction of a low potential species was noted."}
{"id": "PMID:204649", "title": "The electronic state of heme in cytochrome oxidase II. Oxidation-reduction potential interactions and heme iron spin state behavior observed in reductive titrations.", "content": "Magnetic circular dichroism (MCD), electron paramagnetic resonance (EPR), and optical absorption spectroscopies have been used to monitor the concentrations of oxidized and reduced heme and copper during stoichiometric reductive titrations of purified beef heart cytochrome oxidase. The MCD data are deconvoluted to obtain the concentrations of reduced cytochromes a and a3 during the titrations; analysis of the EPR spectra provides complementary data on the concentrations of the EPR-detectable species. For the native enzyme in the absence of exogenous ligands, cytochromes a and a3 are reduced to approximately the same extent at all points in the titration. The reduction of the EPR-detectable copper, on the other hand, initially lags the reduction of the two cytochromes but in the final stages of the titration is completely reduced prior to either cytochrome a or a3. These non-Nernstian titration results are interpreted to indicate that the primary mode of heme-heme interaction in cytochrome oxidase involves shifts in oxidation-reduction potential for each of the two cytochromes such that a change in oxidation state for one of the hemes lowers the oxidation-reduction potential of the second heme by approximately 135 mV. In these titrations high spin species are detected which account for 0.25 spin/oxidase maximally. Evidence is presented to indicate that at least some of these signals can be attributed to cytochrome a3+ which has undergone a low-spin to high-spin state transition in the course of the titration. In the presence of carbon monoxide the oxidation-reduction properties of cytochromes a and a3 are markedly altered. The a32+. CO complex is fully formed prior to reduction of either cytochrome a3+ or the EPR-detectable copper. The g = 3 EPR signal attributed to cytochrome a3+ decreases as the MCD intensity of cytochrome a2+ increases; no significant high-spin intensity is observed at any intermediate stage of reduction. We interpret these Nernstian titration results to indicate that in the presence of ligands the oxidation-reduction potential of cytochrome a relative to cytochrome a3 is determined by the oxidation-reduction state of the stabilized cytochrome a3 ligand complex; if ligand binding occurs to reduced cytochrome a3 then cytochrome a titrates with a lower potential; cytochrome a titrates with a higher potential if oxidized cytochrome a3 is stabilized by ligand binding.", "contents": "The electronic state of heme in cytochrome oxidase II. Oxidation-reduction potential interactions and heme iron spin state behavior observed in reductive titrations. Magnetic circular dichroism (MCD), electron paramagnetic resonance (EPR), and optical absorption spectroscopies have been used to monitor the concentrations of oxidized and reduced heme and copper during stoichiometric reductive titrations of purified beef heart cytochrome oxidase. The MCD data are deconvoluted to obtain the concentrations of reduced cytochromes a and a3 during the titrations; analysis of the EPR spectra provides complementary data on the concentrations of the EPR-detectable species. For the native enzyme in the absence of exogenous ligands, cytochromes a and a3 are reduced to approximately the same extent at all points in the titration. The reduction of the EPR-detectable copper, on the other hand, initially lags the reduction of the two cytochromes but in the final stages of the titration is completely reduced prior to either cytochrome a or a3. These non-Nernstian titration results are interpreted to indicate that the primary mode of heme-heme interaction in cytochrome oxidase involves shifts in oxidation-reduction potential for each of the two cytochromes such that a change in oxidation state for one of the hemes lowers the oxidation-reduction potential of the second heme by approximately 135 mV. In these titrations high spin species are detected which account for 0.25 spin/oxidase maximally. Evidence is presented to indicate that at least some of these signals can be attributed to cytochrome a3+ which has undergone a low-spin to high-spin state transition in the course of the titration. In the presence of carbon monoxide the oxidation-reduction properties of cytochromes a and a3 are markedly altered. The a32+. CO complex is fully formed prior to reduction of either cytochrome a3+ or the EPR-detectable copper. The g = 3 EPR signal attributed to cytochrome a3+ decreases as the MCD intensity of cytochrome a2+ increases; no significant high-spin intensity is observed at any intermediate stage of reduction. We interpret these Nernstian titration results to indicate that in the presence of ligands the oxidation-reduction potential of cytochrome a relative to cytochrome a3 is determined by the oxidation-reduction state of the stabilized cytochrome a3 ligand complex; if ligand binding occurs to reduced cytochrome a3 then cytochrome a titrates with a lower potential; cytochrome a titrates with a higher potential if oxidized cytochrome a3 is stabilized by ligand binding."}
{"id": "PMID:204650", "title": "Molecular symmetry of fructose-1,6-diphosphatase by X-ray diffraction analysis.", "content": "Large single crystals of rabbit liver fructose-1,6-diphosphatase suitable for a high resolution structure analysis have been grown from polyethylene glycol. The space group of these crystals is I222 with a = 75 A, b = 81 A, and c = 132 A and there are 2 tetrameric molecules in the unit cell. These crystals have one protein subunit as the crystallographic asymmetric unit and establish point group symmetry 222 as the molecular symmetry.", "contents": "Molecular symmetry of fructose-1,6-diphosphatase by X-ray diffraction analysis. Large single crystals of rabbit liver fructose-1,6-diphosphatase suitable for a high resolution structure analysis have been grown from polyethylene glycol. The space group of these crystals is I222 with a = 75 A, b = 81 A, and c = 132 A and there are 2 tetrameric molecules in the unit cell. These crystals have one protein subunit as the crystallographic asymmetric unit and establish point group symmetry 222 as the molecular symmetry."}
{"id": "PMID:204651", "title": "Insulin regulation of Leydig cell luteinizing hormone receptors.", "content": "The effect of experimentally induced diabetes on the luteinizing hormone-human chorionic gonadotropin receptors in rat testes was examined. Pancreatectomy and streptozotocin diabetes the gonadotropin receptors and the administration of insulin restored the binding capacity to normal values. No differences in the association constant as well as the sedimentation coefficients of the luteinizing hormone-human chorionic gonadotropin receptor complexes were observed between normal and diabetic animals.", "contents": "Insulin regulation of Leydig cell luteinizing hormone receptors. The effect of experimentally induced diabetes on the luteinizing hormone-human chorionic gonadotropin receptors in rat testes was examined. Pancreatectomy and streptozotocin diabetes the gonadotropin receptors and the administration of insulin restored the binding capacity to normal values. No differences in the association constant as well as the sedimentation coefficients of the luteinizing hormone-human chorionic gonadotropin receptor complexes were observed between normal and diabetic animals."}
{"id": "PMID:204652", "title": "The soluble \"high potential\" type iron-sulfur protein from mitochondria is aconitase.", "content": "Properties of soluble high potential type iron-sulfur protein (HiPIP) from beef heart mitochondria were compared to those of aconitase from pig heart. The two proteins when purified to homogeneity by the criteria of sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis show identical light absorption characteristics. EPR signals of the HiPIP type centered at g = 2.01 when oxidized, isoelectric points at pH 8.5 to 8.6, are inseparable by SDS-polyacrylamide electrophoresis, and exhibit aconitase activity when activated by reducing agents in the presence of ferrous iron. The requirement for activation goes parallel to the intensity of the signal from the oxidized iron-sulfur cluster, i.e. the cluster is reduced in the active enzyme. We conclude that the soluble mitochondrial HiPIP is identical with aconitase. The relationships of iron to labile sulfide, molecular weight and unpaired spins in the EPR signal, and implications of our findings for the role of iron in aconitase are discussed.", "contents": "The soluble \"high potential\" type iron-sulfur protein from mitochondria is aconitase. Properties of soluble high potential type iron-sulfur protein (HiPIP) from beef heart mitochondria were compared to those of aconitase from pig heart. The two proteins when purified to homogeneity by the criteria of sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis show identical light absorption characteristics. EPR signals of the HiPIP type centered at g = 2.01 when oxidized, isoelectric points at pH 8.5 to 8.6, are inseparable by SDS-polyacrylamide electrophoresis, and exhibit aconitase activity when activated by reducing agents in the presence of ferrous iron. The requirement for activation goes parallel to the intensity of the signal from the oxidized iron-sulfur cluster, i.e. the cluster is reduced in the active enzyme. We conclude that the soluble mitochondrial HiPIP is identical with aconitase. The relationships of iron to labile sulfide, molecular weight and unpaired spins in the EPR signal, and implications of our findings for the role of iron in aconitase are discussed."}
{"id": "PMID:204653", "title": "Cytidine 3':5'-monophosphate phosphodiesterase in mammalian tissues. Occurrence and biological involvement.", "content": "A phosphodiesterase activity that preferentially hydrolyzed cytidine 3':5'-monophosphate was partially purified from rat liver extract. The enzyme was best activated by Fe2+ (5 to 10 mM). Mn2+ and Mg2+ were less effective, whereas Zn2+, Co2+, and Ca2+ were ineffective. It exhibited kinetics typical of a high Km phosphodiesterase, with a Km for cycli CMP of 2.4 mM. The enzyme, inhibited by theophylline and 1-methyl-3-isobutyl xanthine to much less extents than cyclic AMP and cyclic GMP phosphodiesterases, was found in all rat tissues examined, with highest levels seen in the liver, kidney, and intestine, and lowest levels found in the skeletal muscle, cerebellum, aorta, and blood cells. The enzyme levels in the regenerating liver were found to be about 40% lower than the control liver of rats; they were also 3 to 10 times lower in the fetal liver, lung, and heart than the corresponding adult tissues of guinea pigs. These findings suggest that depressed cyclic CMP phosphodiesterase may be in part related to cell proliferation, in line with reports that the regenerating liver has higher levels of cyclic CMP (Bloch, A. (1975) Adv. Cycli Nucleotide Res. 5, 331-338) and cytidylate cyclase (Cech, S. Y., and Ignarro, L.J. (1977) Science 198, 1063-1065).", "contents": "Cytidine 3':5'-monophosphate phosphodiesterase in mammalian tissues. Occurrence and biological involvement. A phosphodiesterase activity that preferentially hydrolyzed cytidine 3':5'-monophosphate was partially purified from rat liver extract. The enzyme was best activated by Fe2+ (5 to 10 mM). Mn2+ and Mg2+ were less effective, whereas Zn2+, Co2+, and Ca2+ were ineffective. It exhibited kinetics typical of a high Km phosphodiesterase, with a Km for cycli CMP of 2.4 mM. The enzyme, inhibited by theophylline and 1-methyl-3-isobutyl xanthine to much less extents than cyclic AMP and cyclic GMP phosphodiesterases, was found in all rat tissues examined, with highest levels seen in the liver, kidney, and intestine, and lowest levels found in the skeletal muscle, cerebellum, aorta, and blood cells. The enzyme levels in the regenerating liver were found to be about 40% lower than the control liver of rats; they were also 3 to 10 times lower in the fetal liver, lung, and heart than the corresponding adult tissues of guinea pigs. These findings suggest that depressed cyclic CMP phosphodiesterase may be in part related to cell proliferation, in line with reports that the regenerating liver has higher levels of cyclic CMP (Bloch, A. (1975) Adv. Cycli Nucleotide Res. 5, 331-338) and cytidylate cyclase (Cech, S. Y., and Ignarro, L.J. (1977) Science 198, 1063-1065)."}
{"id": "PMID:204654", "title": "Demonstration, in leukemia L-1210 cells, of a phosphodiesterase acting on 3':5'-cyclic CMP but not on 3':5'-cyclic AMP or 3':5'-cyclic GMP.", "content": "cCMP-specific phosphodiesterase activity was demonstrated in the 80 to 100% ammonium sulfate fraction obtained from disrupted leukemia L-1210 cells. The activity was linear with time (up to 60 min), was a function of protein concentration, and was markedly stimulated by Mg2+ and by ammonium sulfate. Under identical assay conditions, no significant hydrolysis of cAMP or cGMP was observed, although these cyclic nucleotides served as substrates for phosphodiesterase(s) present in all the fractions obtained by less than 80% ammonium sulfate saturation. This is the first demonstration of a cCMP-specific phosphodiesterase.", "contents": "Demonstration, in leukemia L-1210 cells, of a phosphodiesterase acting on 3':5'-cyclic CMP but not on 3':5'-cyclic AMP or 3':5'-cyclic GMP. cCMP-specific phosphodiesterase activity was demonstrated in the 80 to 100% ammonium sulfate fraction obtained from disrupted leukemia L-1210 cells. The activity was linear with time (up to 60 min), was a function of protein concentration, and was markedly stimulated by Mg2+ and by ammonium sulfate. Under identical assay conditions, no significant hydrolysis of cAMP or cGMP was observed, although these cyclic nucleotides served as substrates for phosphodiesterase(s) present in all the fractions obtained by less than 80% ammonium sulfate saturation. This is the first demonstration of a cCMP-specific phosphodiesterase."}
{"id": "PMID:204658", "title": "The indispensability of phospholipid and ubiquinone in mitochondrial electron transfer from succinate to cytochrome c.", "content": "The indispensability of phospholipid and ubiquinone (Q) in mitochondrial electron transfer was studied by depleting phospholipid and Q in succinate-cytochrome c reductase and then replenishing the depleted enzyme. More than 90% of phospholipid and Q was removed by repeated ammonium sulfate-cholate fractionation. The depleted succinate-cytochrome c reductase showed no enzymatic activity for succinate leads to c or QH2 leads to c and yet retained most of the succinate leads to Q activity. All enzymatic activity was restored upon the addition of Q and phospholipid. Restoration required the addition of Q prior to the addition of phospholipid. Reversing the addition sequence or addition of a mixture of phospholipid and Q resulted only in a small restoration of activities. The conditions for restoration are given in detail. Removal of phospholipid from succinate-cytochrome c reductase resulted in reduction of cytochrome c1 in the absence of exogenous electron donor. Replenishing the preparation with phospholipid brought about the reoxidation of cytochrome c1 in the absence of electron acceptor or oxygen.", "contents": "The indispensability of phospholipid and ubiquinone in mitochondrial electron transfer from succinate to cytochrome c. The indispensability of phospholipid and ubiquinone (Q) in mitochondrial electron transfer was studied by depleting phospholipid and Q in succinate-cytochrome c reductase and then replenishing the depleted enzyme. More than 90% of phospholipid and Q was removed by repeated ammonium sulfate-cholate fractionation. The depleted succinate-cytochrome c reductase showed no enzymatic activity for succinate leads to c or QH2 leads to c and yet retained most of the succinate leads to Q activity. All enzymatic activity was restored upon the addition of Q and phospholipid. Restoration required the addition of Q prior to the addition of phospholipid. Reversing the addition sequence or addition of a mixture of phospholipid and Q resulted only in a small restoration of activities. The conditions for restoration are given in detail. Removal of phospholipid from succinate-cytochrome c reductase resulted in reduction of cytochrome c1 in the absence of exogenous electron donor. Replenishing the preparation with phospholipid brought about the reoxidation of cytochrome c1 in the absence of electron acceptor or oxygen."}
{"id": "PMID:204660", "title": "Partial purification and properties of the Epstein-Barr virus-associated nuclear antigen.", "content": "The Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) was purified 85-fold from a nuclear pellet derived from an EBV-transformed B lyphoblastoid cell line by a five-step procedure consisting of preparation of extract, heating at 80 degrees C in phosphate buffer, ammonium sulfate precipitation, preparative ultracentrifugation, and affinity chromatography on double-stranded DNA-cellulose. The purified complement fixing antigen specifically blocked the anticomplement immunofluorescence assay for EBNA. Several properties indicate a close association of EBNA with chromatin, viz. 1) precipitation of antigenic activity by phosphate buffer and subsequent thermal fractionation; 2) partial sensitivity of antigenic activity to DNase (but not to RNase) and restoration of activity by addition of calf thymus DNA; and 3) specific binding of EBNA to double-stranded DNA-cellulose. Other properties of EBNA, including its unusual heat stability, are described.", "contents": "Partial purification and properties of the Epstein-Barr virus-associated nuclear antigen. The Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) was purified 85-fold from a nuclear pellet derived from an EBV-transformed B lyphoblastoid cell line by a five-step procedure consisting of preparation of extract, heating at 80 degrees C in phosphate buffer, ammonium sulfate precipitation, preparative ultracentrifugation, and affinity chromatography on double-stranded DNA-cellulose. The purified complement fixing antigen specifically blocked the anticomplement immunofluorescence assay for EBNA. Several properties indicate a close association of EBNA with chromatin, viz. 1) precipitation of antigenic activity by phosphate buffer and subsequent thermal fractionation; 2) partial sensitivity of antigenic activity to DNase (but not to RNase) and restoration of activity by addition of calf thymus DNA; and 3) specific binding of EBNA to double-stranded DNA-cellulose. Other properties of EBNA, including its unusual heat stability, are described."}
{"id": "PMID:204662", "title": "Immune adherence hemagglutination test applied to the study of herpes simplex and varicella-zoster virus infections.", "content": "The immune adherence hemagglutination (IAHA) test has been used successfully to detect antibody to herpes simplex (HS) virus and varicella-zoster (V-Z) virus. Comparative studies between the complement-fixation (CF) test and the IAHA test revealed that, in most cases, the IAHA test was more sensitive than the CF test. Furthermore, diagnosis on the basis of a fourfold change in antibody titer was made more rapidly by the IAHA test. The IAHA test was found to be a very simple and practical technique requiring only a few hours for completion compared with the conventional CF test which required up to 24 h. In addition, both sera and cerebrospinal fluids could be tested in very low dilutions in the IAHA test, so that very low levels of antibody could be detected. Also, the IAHA test detected antibody to V-Z virus more frequently than did the CF test in adults with a history of varicella occurring 9 to 30 years prior to sampling. The level of cross-reaction between HS and V-Z viruses was examined by both the CF test and the IAHA test, and no major differences between the two techniques were found.", "contents": "Immune adherence hemagglutination test applied to the study of herpes simplex and varicella-zoster virus infections. The immune adherence hemagglutination (IAHA) test has been used successfully to detect antibody to herpes simplex (HS) virus and varicella-zoster (V-Z) virus. Comparative studies between the complement-fixation (CF) test and the IAHA test revealed that, in most cases, the IAHA test was more sensitive than the CF test. Furthermore, diagnosis on the basis of a fourfold change in antibody titer was made more rapidly by the IAHA test. The IAHA test was found to be a very simple and practical technique requiring only a few hours for completion compared with the conventional CF test which required up to 24 h. In addition, both sera and cerebrospinal fluids could be tested in very low dilutions in the IAHA test, so that very low levels of antibody could be detected. Also, the IAHA test detected antibody to V-Z virus more frequently than did the CF test in adults with a history of varicella occurring 9 to 30 years prior to sampling. The level of cross-reaction between HS and V-Z viruses was examined by both the CF test and the IAHA test, and no major differences between the two techniques were found."}
{"id": "PMID:204663", "title": "Enzyme-linked immunosorbent assay for detection of hepatitis A antigen in stool and antibody to hepatitis A antigen in sera: comparison with solid-phase radioimmunoassay, immune electron microscopy, and immune adherence hemagglutination assay.", "content": "Previously described techniques for detection of hepatitis A antigen (HA Ag) and antibody (anti-HA) have required purified HA Ag and expensive equipment. Herein is described an enzyme-linked immunosorbent assay (ELISA) for specific detection of HA Ag in human stool filtrates and of anti-HA in sera by using selected HA Ag-containing human stool filtrates as the antigen source. Because human stools often react nonspecifically in serological tests for HA Ag, blocking with preexposure and hyperimmune anti-HA sera from a chimpanzee inoculated with hepatitis A virus was used to confirm specific detection of HA Ag. The sensitivity of ELISA was found to be comparable to that of solid-phase radioimmunoassay (SPRIA) and immune electron microscopy (IEM). Of 37 acute-phase stools collected from nine patients, 16 were positive for HA Ag by ELISA. In 13 of these, HA Ag particles were found by IEM, and an additional 3 stools negative by ELISA contained HA Ag particles by IEM. Eight control stools were negative by both ELISA and IEM. Anti-HA was measured in sera by demonstrating its ability to block binding of the enzyme conjugate to HA Ag in a stool without detectable nonspecificity. This test (blocking ELISA) was as sensitive and specific as blocking SPIRA, IEM, and immune adherence hemagglutination and, like SPRIA and IEM, detected early-developing antibody. The ELISA is simple to perform and requires only a minimum of equipment. It is useful for screening stools for HA Ag and for monitoring HA Ag during purification, as well as for detecting early and late anti-HA in sera.", "contents": "Enzyme-linked immunosorbent assay for detection of hepatitis A antigen in stool and antibody to hepatitis A antigen in sera: comparison with solid-phase radioimmunoassay, immune electron microscopy, and immune adherence hemagglutination assay. Previously described techniques for detection of hepatitis A antigen (HA Ag) and antibody (anti-HA) have required purified HA Ag and expensive equipment. Herein is described an enzyme-linked immunosorbent assay (ELISA) for specific detection of HA Ag in human stool filtrates and of anti-HA in sera by using selected HA Ag-containing human stool filtrates as the antigen source. Because human stools often react nonspecifically in serological tests for HA Ag, blocking with preexposure and hyperimmune anti-HA sera from a chimpanzee inoculated with hepatitis A virus was used to confirm specific detection of HA Ag. The sensitivity of ELISA was found to be comparable to that of solid-phase radioimmunoassay (SPRIA) and immune electron microscopy (IEM). Of 37 acute-phase stools collected from nine patients, 16 were positive for HA Ag by ELISA. In 13 of these, HA Ag particles were found by IEM, and an additional 3 stools negative by ELISA contained HA Ag particles by IEM. Eight control stools were negative by both ELISA and IEM. Anti-HA was measured in sera by demonstrating its ability to block binding of the enzyme conjugate to HA Ag in a stool without detectable nonspecificity. This test (blocking ELISA) was as sensitive and specific as blocking SPIRA, IEM, and immune adherence hemagglutination and, like SPRIA and IEM, detected early-developing antibody. The ELISA is simple to perform and requires only a minimum of equipment. It is useful for screening stools for HA Ag and for monitoring HA Ag during purification, as well as for detecting early and late anti-HA in sera."}
{"id": "PMID:204664", "title": "Hepatocellular carcinoma and hepatic cirrhosis in the west of Scotland: a 25-year necropsy review.", "content": "A two-fold increase in the incidence of hepatocellular carcinoma in the west of Scotland is reported on the basis of a 25-year retrospective necropsy review (313 cases). This increase is not accompanied by a corresponding increase in the incidence of hepatic cirrhosis. The relationship between hepatocellular carcinoma and hepatic cirrhosis is discussed in the light of these findings.", "contents": "Hepatocellular carcinoma and hepatic cirrhosis in the west of Scotland: a 25-year necropsy review. A two-fold increase in the incidence of hepatocellular carcinoma in the west of Scotland is reported on the basis of a 25-year retrospective necropsy review (313 cases). This increase is not accompanied by a corresponding increase in the incidence of hepatic cirrhosis. The relationship between hepatocellular carcinoma and hepatic cirrhosis is discussed in the light of these findings."}
{"id": "PMID:204665", "title": "Routine diagnosis of human rotaviruses in stools.", "content": "Electron microscopy, immune electron microscopy and complement fixation as methods of detecting rotavirus in the stools of young children with gastroenteritis were compared in a blind study during the winter of 1975-6. Complement fixation was the simplest to perform, was as sensitive as the other two, and allowed a quantitative measurement of viral excretion. Absorption of faecal extracts with fetal calf serum usually removed the anticomplementary activity of faecal extracts.", "contents": "Routine diagnosis of human rotaviruses in stools. Electron microscopy, immune electron microscopy and complement fixation as methods of detecting rotavirus in the stools of young children with gastroenteritis were compared in a blind study during the winter of 1975-6. Complement fixation was the simplest to perform, was as sensitive as the other two, and allowed a quantitative measurement of viral excretion. Absorption of faecal extracts with fetal calf serum usually removed the anticomplementary activity of faecal extracts."}
{"id": "PMID:204666", "title": "Laboratory diagnosis of EB virus infection in some cases presenting as hepatitis.", "content": "In 1975 and 1976, 7580 serum specimens were tested for HBsAg by the passive haemagglutination test, Hepanosticon. Serum from 38 people gave a positive result after absorption with the absorbent provided, but the presence of HBsAg could not be confirmed by other tests. Tests for current infection with EB virus, namely, the presence of heterophil antibody and EB virus specific IgM, were performed and were positive in 11 of the 38. In six of these the clinical picture was of hepatitis rather than infectious mononucleosis.", "contents": "Laboratory diagnosis of EB virus infection in some cases presenting as hepatitis. In 1975 and 1976, 7580 serum specimens were tested for HBsAg by the passive haemagglutination test, Hepanosticon. Serum from 38 people gave a positive result after absorption with the absorbent provided, but the presence of HBsAg could not be confirmed by other tests. Tests for current infection with EB virus, namely, the presence of heterophil antibody and EB virus specific IgM, were performed and were positive in 11 of the 38. In six of these the clinical picture was of hepatitis rather than infectious mononucleosis."}
{"id": "PMID:204667", "title": "Changes in peripheral nerve function with long-term hemofiltration treatment.", "content": "The changes in the peripheral nerve function of three patients with chronic renal failure who were treated over a period of 1-1/2 to 2 years by hemofiltration have been analyzed in the form of a longitudinal study by quantitative measurements of vibratory perception threshold and nerve conduction velocity. Changes in vibratory perception threshold were measured in six patients both before and after treatment. Despite increased values of creatinine and BUN, an improvement in the peripheral nerve function of all patients undergoing hemofiltration could be observed, although vibratory perception and nerve conduction velocity did not return to normal. All of the vibratory perception threshold measurements made directly after hemofiltration showed an improved vibratory perception in comparison to the original values. A comparison of the measurement methods showed a good correlation and clearly indicated the advantage of vibratory perception threshold measurements as a means for the routine diagnosis of nephrogenic polyneuropathy.", "contents": "Changes in peripheral nerve function with long-term hemofiltration treatment. The changes in the peripheral nerve function of three patients with chronic renal failure who were treated over a period of 1-1/2 to 2 years by hemofiltration have been analyzed in the form of a longitudinal study by quantitative measurements of vibratory perception threshold and nerve conduction velocity. Changes in vibratory perception threshold were measured in six patients both before and after treatment. Despite increased values of creatinine and BUN, an improvement in the peripheral nerve function of all patients undergoing hemofiltration could be observed, although vibratory perception and nerve conduction velocity did not return to normal. All of the vibratory perception threshold measurements made directly after hemofiltration showed an improved vibratory perception in comparison to the original values. A comparison of the measurement methods showed a good correlation and clearly indicated the advantage of vibratory perception threshold measurements as a means for the routine diagnosis of nephrogenic polyneuropathy."}
{"id": "PMID:204668", "title": "The glucagonoma syndrome.", "content": "The glucagonoma syndrome is characterized by necrolytic migratory erythema, glossitis, ungual dystrophy, diabetes mellitus, anemia, weight loss, elevated plasma glucagon levels and an alpha-cell glucagon-secreting neoplasm of the pancreas. We are reporting a case of this syndrome in a middle-aged woman, in whom the first complaints and signs were cutaneous. The recognition of the distinctive skin manifestations of the syndrome led to early diagnosis and treatment of the underlying malignant pancreatic tumor.", "contents": "The glucagonoma syndrome. The glucagonoma syndrome is characterized by necrolytic migratory erythema, glossitis, ungual dystrophy, diabetes mellitus, anemia, weight loss, elevated plasma glucagon levels and an alpha-cell glucagon-secreting neoplasm of the pancreas. We are reporting a case of this syndrome in a middle-aged woman, in whom the first complaints and signs were cutaneous. The recognition of the distinctive skin manifestations of the syndrome led to early diagnosis and treatment of the underlying malignant pancreatic tumor."}
{"id": "PMID:204704", "title": "Microspectrophotometric quantitation of the diaminobenzidine reaction for histochemical demonstration of cytochrome oxidase activity.", "content": "Polyacrylamide models in which an extract of cattle heart mitochondria was incorporated, as well as cryostat sections of tongue muscle and epithelium, were used to set up the conditions under which the histochemical reaction for the demonstration of cytochrome oxidase can be quantitated. Using diaminobenzidine in a concentration of 5.5 mM, cytochrome C in a fixed concentration of 76 micron and keeping the incubation medium away from direct light action, enzyme activity can be evaluated by means of direct microphotometry on tissue sections. Each biologic model requires previous individual determination of the measurement limits. These limits can be readily established by using a small chamber for the incubation medium, which can be placed in the microphotometer, allowing the reaction rate to be following using a single section.", "contents": "Microspectrophotometric quantitation of the diaminobenzidine reaction for histochemical demonstration of cytochrome oxidase activity. Polyacrylamide models in which an extract of cattle heart mitochondria was incorporated, as well as cryostat sections of tongue muscle and epithelium, were used to set up the conditions under which the histochemical reaction for the demonstration of cytochrome oxidase can be quantitated. Using diaminobenzidine in a concentration of 5.5 mM, cytochrome C in a fixed concentration of 76 micron and keeping the incubation medium away from direct light action, enzyme activity can be evaluated by means of direct microphotometry on tissue sections. Each biologic model requires previous individual determination of the measurement limits. These limits can be readily established by using a small chamber for the incubation medium, which can be placed in the microphotometer, allowing the reaction rate to be following using a single section."}
{"id": "PMID:204705", "title": "Bluetongue studies with sentinel cattle in Kenya.", "content": "Bluetongue antibody of 19 different serological types was found in a group of sentinel cattle near Nairobi. A continuous challenge by these 19 strains occurred each year in this location. The sero-conversion rates were shown to vary from year to year and rainfall had no obvious effect upon the conversion rates. The 19 different strains of virus were also shown to be active at five widely scattered sites in different parts of the country.", "contents": "Bluetongue studies with sentinel cattle in Kenya. Bluetongue antibody of 19 different serological types was found in a group of sentinel cattle near Nairobi. A continuous challenge by these 19 strains occurred each year in this location. The sero-conversion rates were shown to vary from year to year and rainfall had no obvious effect upon the conversion rates. The 19 different strains of virus were also shown to be active at five widely scattered sites in different parts of the country."}
{"id": "PMID:204707", "title": "Scanning electron microscopic appearance of viral-antigen-coated polystyrene balls.", "content": "A radioimmunoassay (RIA) was recently developed for the detection of antiviral IgG and IgM class-specific antibodies using antigen-coated polystyrene balls as the RIA solid-phase. In this communication the attachment and distribution of herpes simplex virus (HSV) capsid and envelope antigens and rubella viruses on the surface of the balls was examined by scanning electron microscopy (SEM). In SEM the surface of the untreated 'clear frosted' polystyrene balls appeared very uneven with innumerable pits and grooves. The viral particles were haphazardly distributed both in the grooves and on the exposed surface of the balls. The strength of adsorption of the viral antigens onto the balls seemed to be remarkably resistant to outside mechanical forces. HSV antigens frequently appeared in clusters, whereas rubella viruses were mostly found as single particles.", "contents": "Scanning electron microscopic appearance of viral-antigen-coated polystyrene balls. A radioimmunoassay (RIA) was recently developed for the detection of antiviral IgG and IgM class-specific antibodies using antigen-coated polystyrene balls as the RIA solid-phase. In this communication the attachment and distribution of herpes simplex virus (HSV) capsid and envelope antigens and rubella viruses on the surface of the balls was examined by scanning electron microscopy (SEM). In SEM the surface of the untreated 'clear frosted' polystyrene balls appeared very uneven with innumerable pits and grooves. The viral particles were haphazardly distributed both in the grooves and on the exposed surface of the balls. The strength of adsorption of the viral antigens onto the balls seemed to be remarkably resistant to outside mechanical forces. HSV antigens frequently appeared in clusters, whereas rubella viruses were mostly found as single particles."}
{"id": "PMID:204708", "title": "Epinephrine activation of pig skin adenylate cyclase in vivo and subsequent refractoriness to activation.", "content": "Epinephrine injected intradermally activated pig skin adenylate cyclase and increased the epidermal cyclic AMP level in vivo. This biphasic response reached a maximum in 5 min and gradually decreased thereafter. The simultaneous injection of a cyclic AMP phosphodiesterase inhibitor, isobutyl methyl xanthin (IBMX) potentiated the increase. The simultaneous injection of a specific beta-adrenergic receptor inhibitor, propranolol, inhibited this accumulation of cyclic AMP. After the first activation by epinephrine in vivo, there was a marked refractoriness of the skin (epidermal) adenylate cyclase to subsequent epinephrine stimulation vivo and in vitro. This refractoriness was specific for catecholamine stimulation as responses to histamine were normal. Recovery from refractoriness started at 48 hr and was completed at 1 week after the injection of epinephrine.", "contents": "Epinephrine activation of pig skin adenylate cyclase in vivo and subsequent refractoriness to activation. Epinephrine injected intradermally activated pig skin adenylate cyclase and increased the epidermal cyclic AMP level in vivo. This biphasic response reached a maximum in 5 min and gradually decreased thereafter. The simultaneous injection of a cyclic AMP phosphodiesterase inhibitor, isobutyl methyl xanthin (IBMX) potentiated the increase. The simultaneous injection of a specific beta-adrenergic receptor inhibitor, propranolol, inhibited this accumulation of cyclic AMP. After the first activation by epinephrine in vivo, there was a marked refractoriness of the skin (epidermal) adenylate cyclase to subsequent epinephrine stimulation vivo and in vitro. This refractoriness was specific for catecholamine stimulation as responses to histamine were normal. Recovery from refractoriness started at 48 hr and was completed at 1 week after the injection of epinephrine."}
{"id": "PMID:204709", "title": "Experimental infection of Tupaia belangeri (tree shrews) with herpes simplex virus types 1 and 2.", "content": "The susceptibility of Tupaia belangeri (tree shrews, which are primitive prosimian primates) to infection with herpes simplex virus (HSV) and the pathogenesis of HSV in these animals were investigated. Juvenile (28--45 days old) and adult (150 days old) animals were inoculated intravenously, intraperitoneally, or subcutaneously with HSV type 1 or 2 (25--10(5) plaque-forming units per animal). Clinical illness usually appeared in juvenile animals on the second day after inoculation, and the animals died between two and 14 days after inoculation. High titers of infectious HSV were recovered from liver and spleen. The histopathologic examination always showed severe liver changes with numerous necrotic areas. The morphologic events in the liver were designated as herpetic hepatitis. The next most common morphologic findings were encephalitis and fibrosis in the spleen. These results demonstrate the high pathogenicity of HSV types 1 and 2 in juvenile T. belangeri. In contrast, adult animals did not develop acute clinical disease and survived the HSV infection.", "contents": "Experimental infection of Tupaia belangeri (tree shrews) with herpes simplex virus types 1 and 2. The susceptibility of Tupaia belangeri (tree shrews, which are primitive prosimian primates) to infection with herpes simplex virus (HSV) and the pathogenesis of HSV in these animals were investigated. Juvenile (28--45 days old) and adult (150 days old) animals were inoculated intravenously, intraperitoneally, or subcutaneously with HSV type 1 or 2 (25--10(5) plaque-forming units per animal). Clinical illness usually appeared in juvenile animals on the second day after inoculation, and the animals died between two and 14 days after inoculation. High titers of infectious HSV were recovered from liver and spleen. The histopathologic examination always showed severe liver changes with numerous necrotic areas. The morphologic events in the liver were designated as herpetic hepatitis. The next most common morphologic findings were encephalitis and fibrosis in the spleen. These results demonstrate the high pathogenicity of HSV types 1 and 2 in juvenile T. belangeri. In contrast, adult animals did not develop acute clinical disease and survived the HSV infection."}
{"id": "PMID:204710", "title": "Rotavirus in travelers' diarrhea: study of an adult student population in Mexico.", "content": "The role of rotavirus in adult diarrhea was evaluated in 165 students attending a Mexican university. Students were divided into three groups: newly arrived summer students from the United Sttes, regular students from the United States, and Mexican and Venezuelan students. Ninety-one students with diarrhea and 74 corresponding, matched, asymptomatic control students were included in the study. The frequency of rotavirus in stools was determined by electron microscopy with use of the pseudoreplica technique. Twenty-five percent of those who were ill and 12% of the controls had rotavirus in their stools. A significantly (P less than 0.05) greater number of newly arrived United States summer students with diarrhea had rotavirus in their stool than did matched controls (26% vs. 3%). There was no significant difference in rate of recovery of bacterial pathogens from rotavirus-positive and rotavirus-negative stools (52% vs. 53%) from students with diarrhea. Although significantly more rotavirus was identified from ill American summer students than from controls, the role of rotavirus as a cause of diarrhea in these students could not be established in all cases since bacterial pathogens were also commonly found in stool.", "contents": "Rotavirus in travelers' diarrhea: study of an adult student population in Mexico. The role of rotavirus in adult diarrhea was evaluated in 165 students attending a Mexican university. Students were divided into three groups: newly arrived summer students from the United Sttes, regular students from the United States, and Mexican and Venezuelan students. Ninety-one students with diarrhea and 74 corresponding, matched, asymptomatic control students were included in the study. The frequency of rotavirus in stools was determined by electron microscopy with use of the pseudoreplica technique. Twenty-five percent of those who were ill and 12% of the controls had rotavirus in their stools. A significantly (P less than 0.05) greater number of newly arrived United States summer students with diarrhea had rotavirus in their stool than did matched controls (26% vs. 3%). There was no significant difference in rate of recovery of bacterial pathogens from rotavirus-positive and rotavirus-negative stools (52% vs. 53%) from students with diarrhea. Although significantly more rotavirus was identified from ill American summer students than from controls, the role of rotavirus as a cause of diarrhea in these students could not be established in all cases since bacterial pathogens were also commonly found in stool."}
{"id": "PMID:204711", "title": "Hepatitis A virus infection: new insights from seroepidemiologic studies.", "content": "The prevalence of exposure to hepatitis A virus (HAV) increases with increasing age; decreases with increasing socioeconomic class; increases with increasing serologic evidence of prior hepatitis B virus (HBV) exposure but is much more common than HBV exposure; is independent of sex and race; varies in different parts of the world as a function of hygienic, developmental, and unrecognized geographic factors; and is not affected by immune deficiency or immaturity. Transmission of type A hepatitis is enhanced by poor personal hygiene such as that seen in institutions for the mentally retarded. On the other hand, there is no increased exposure to HAV among homosexuals, who have frequent and intimate contact with multiple sexual partners; among hemodialysis patients and staff; or among multiply transfused individuals, all of whom are at significantly increased risk of exposure to HBV. No epidemiologic evidence has confirmed the existence of viremic or intestinal carriers of HAV, and the virus is rarely, if ever, spread by parenteral mechanisms. Finally, HAV appears to play no role in chronic liver disease and a very minor role in fulminant hepatitis; however, HAV is responsible for a sizable proportion (approximately 20%--40%) of sporadic hepatitis among urban adults.", "contents": "Hepatitis A virus infection: new insights from seroepidemiologic studies. The prevalence of exposure to hepatitis A virus (HAV) increases with increasing age; decreases with increasing socioeconomic class; increases with increasing serologic evidence of prior hepatitis B virus (HBV) exposure but is much more common than HBV exposure; is independent of sex and race; varies in different parts of the world as a function of hygienic, developmental, and unrecognized geographic factors; and is not affected by immune deficiency or immaturity. Transmission of type A hepatitis is enhanced by poor personal hygiene such as that seen in institutions for the mentally retarded. On the other hand, there is no increased exposure to HAV among homosexuals, who have frequent and intimate contact with multiple sexual partners; among hemodialysis patients and staff; or among multiply transfused individuals, all of whom are at significantly increased risk of exposure to HBV. No epidemiologic evidence has confirmed the existence of viremic or intestinal carriers of HAV, and the virus is rarely, if ever, spread by parenteral mechanisms. Finally, HAV appears to play no role in chronic liver disease and a very minor role in fulminant hepatitis; however, HAV is responsible for a sizable proportion (approximately 20%--40%) of sporadic hepatitis among urban adults."}
{"id": "PMID:204718", "title": "Measurment of rhesus monkey (Macaca mulatta) apolipoprotein B in serum by radioimmunoassay: comparison of immunoreactivities of rhesus and human low density lipoproteins.", "content": "A sensitive and specific double antibody radio-immunoassay for the major apolipoprotein (apoB) of rhesus (Macaca mulatta) serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. The anti-serum was raised to LDL (d 1.030-1.040 g/ml) and the LDL(2) (d 1.020-1.050 g/ml) was labeled with (125)I by the chloramine-T or iodine monochloride method. The assay, which was sensitive to 0.02-0.5 micro g of LDL(2), had an inter-assay coefficient of variation of 4.5%. This assay was successfully used to measure apoB in the whole serum and low density lipoproteins of control monkeys maintained on a standard Purina monkey chow (PMC) diet and of three groups of monkeys fed atherogenic diets: an \"average American diet,\" a 25% peanut oil and 2% cholesterol-supplemented PMC diet, and a 25% coconut oil and 2% cholesterol-supplemented PMC diet. The control monkeys (n = 13) had a serum cholesterol of 146 +/- 28 mg/dl and an apoB of 50 +/- 18 mg/dl. In the monkeys maintained on the atherogenic diets the serum apoB was elevated: 103 +/- 28 mg/dl (American), 102 +/- 35 mg/dl (peanut oil), and 312 +/- 88 mg/dl (coconut oil). The values for serum total cholesterol were 333 +/- 65 mg/dl (American), 606 +/- 212 mg/dl (peanut oil), and 864 +/- 233 mg/dl (coconut oil) and were elevated relative to controls (P < 0.001). For each of the diets, total serum cholesterol correlated with serum apoB (P < 0.001). The slopes of the regression lines of serum apoB vs. cholesterol for the monkeys on the PMC, American, and coconut oil diets were similar (m = 0.531, 0.401, and 0.359, respectively), but differed from that of monkeys on the peanut oil diet (m = 0.121). The immunoreactivities of rhesus and human LDL were compared using specific antisera raised against these antigens. In homologous assay systems, monkey and human LDL exhibited unique immunological determinants. The same results were obtained with the delipidated preparations of the two LDLs using antisera raised against either monkey or human apoB. Crossover studies using a heterologous tracer with each anti-serum resulted in the selection of a specific population of antibodies directed against antigenic sites shared by these two LDL species.", "contents": "Measurment of rhesus monkey (Macaca mulatta) apolipoprotein B in serum by radioimmunoassay: comparison of immunoreactivities of rhesus and human low density lipoproteins. A sensitive and specific double antibody radio-immunoassay for the major apolipoprotein (apoB) of rhesus (Macaca mulatta) serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. The anti-serum was raised to LDL (d 1.030-1.040 g/ml) and the LDL(2) (d 1.020-1.050 g/ml) was labeled with (125)I by the chloramine-T or iodine monochloride method. The assay, which was sensitive to 0.02-0.5 micro g of LDL(2), had an inter-assay coefficient of variation of 4.5%. This assay was successfully used to measure apoB in the whole serum and low density lipoproteins of control monkeys maintained on a standard Purina monkey chow (PMC) diet and of three groups of monkeys fed atherogenic diets: an \"average American diet,\" a 25% peanut oil and 2% cholesterol-supplemented PMC diet, and a 25% coconut oil and 2% cholesterol-supplemented PMC diet. The control monkeys (n = 13) had a serum cholesterol of 146 +/- 28 mg/dl and an apoB of 50 +/- 18 mg/dl. In the monkeys maintained on the atherogenic diets the serum apoB was elevated: 103 +/- 28 mg/dl (American), 102 +/- 35 mg/dl (peanut oil), and 312 +/- 88 mg/dl (coconut oil). The values for serum total cholesterol were 333 +/- 65 mg/dl (American), 606 +/- 212 mg/dl (peanut oil), and 864 +/- 233 mg/dl (coconut oil) and were elevated relative to controls (P < 0.001). For each of the diets, total serum cholesterol correlated with serum apoB (P < 0.001). The slopes of the regression lines of serum apoB vs. cholesterol for the monkeys on the PMC, American, and coconut oil diets were similar (m = 0.531, 0.401, and 0.359, respectively), but differed from that of monkeys on the peanut oil diet (m = 0.121). The immunoreactivities of rhesus and human LDL were compared using specific antisera raised against these antigens. In homologous assay systems, monkey and human LDL exhibited unique immunological determinants. The same results were obtained with the delipidated preparations of the two LDLs using antisera raised against either monkey or human apoB. Crossover studies using a heterologous tracer with each anti-serum resulted in the selection of a specific population of antibodies directed against antigenic sites shared by these two LDL species."}
{"id": "PMID:204719", "title": "Effect of temperature and plasma on the exchange of apolipoproteins and phospholipids between rat plasma very low and high density lipoproteins.", "content": "The effect of temperature and plasma on the exchange of apoprotein C and phospholipids between VLDL and HDL was studied using 125I-labeled and 32P-labeled VLDL. Temperature affected the exchange of apoproteins and phospholipids similarly, and both were enhanced by increasing the temperature of incubation to 20 degrees C and higher. The exchange of apoC was almost complete within 5 minutes of incubation and was not influenced by the addition of plasma to the incubation mixture. The exchange of phospholipids occurred much more slowly and was enhanced 5- to 10-fold in the presence of plasma. These results indicate that the exchange of both phospholipids and apoC is dependent on the temperature of the incubation, but that they exchange independently, at least in part. It is suggested that the exchange of apoC occurs through dissociation of the apoprotein from the lipoprotein surface to the water phase, whereas the exchange of phospholipids is mediated mainly by a carrier molecule present in plasma and absent in lipoproteins.", "contents": "Effect of temperature and plasma on the exchange of apolipoproteins and phospholipids between rat plasma very low and high density lipoproteins. The effect of temperature and plasma on the exchange of apoprotein C and phospholipids between VLDL and HDL was studied using 125I-labeled and 32P-labeled VLDL. Temperature affected the exchange of apoproteins and phospholipids similarly, and both were enhanced by increasing the temperature of incubation to 20 degrees C and higher. The exchange of apoC was almost complete within 5 minutes of incubation and was not influenced by the addition of plasma to the incubation mixture. The exchange of phospholipids occurred much more slowly and was enhanced 5- to 10-fold in the presence of plasma. These results indicate that the exchange of both phospholipids and apoC is dependent on the temperature of the incubation, but that they exchange independently, at least in part. It is suggested that the exchange of apoC occurs through dissociation of the apoprotein from the lipoprotein surface to the water phase, whereas the exchange of phospholipids is mediated mainly by a carrier molecule present in plasma and absent in lipoproteins."}
{"id": "PMID:204720", "title": "Chylomicron apoprotein localization within rat intestinal epithelium: studies of normal and impaired lipid absorption.", "content": "Monospecific antisera were produced to two chylomicron apoproteins (apoB, apoA-I) and utilized for indirect immunofluorescent localization of these apoproteins within rat intestinal epithelium during normal and impaired lipid absorption. Isolated intestinal epithelial cells prepared after different periods of lipid absorption from in situ intestinal segments revealed a rapid increase in fluorescence for both apoproteins that filled the entire apical portion of the cell. Prolonged lipid absorption for as long as 5 hr demonstrated sustained immunofluorescence and gave no indication of a depletion of the intestinal mucosa for either apoprotein during normal lipid absorption. [(3)H]Leucine incorporation into mesenteric lymph chylomicron apoproteins showed a linear decrease in specific activity of total chylomicron protein as well as apoB over 4 hr of a continuous lipid infusion indicating sustained active apoprotein synthesis during prolonged lipid absorption. Acetoxycloheximide, a potent inhibitor of protein synthesis, was employed to determine the dynamics of chylomicron apoproteins during an experimental condition of impaired lipid absorption. In animals with inhibited protein synthesis, fluorescence for both apoproteins was present early in the course of lipid absorption; however, at 60 min after the onset of lipid absorption, fluorescence for both apoproteins was absent. Fluorescence for both apoproteins returned during the recovery of protein synthesis. The present studies have confirmed previous results that localized two chylomicron apoproteins within intestinal epithelial cells. The present studies extend these observations and disclose a rapid and sustained synthesis of these apoproteins during prolonged chylomicron formation. During an experimental condition of impaired protein synthesis there was a marked reduction in the mucosal content of both apoA-I and apoB. These results are the first demonstration of impaired mucosal apoprotein synthesis during an experimental model of impaired lipid absorption.", "contents": "Chylomicron apoprotein localization within rat intestinal epithelium: studies of normal and impaired lipid absorption. Monospecific antisera were produced to two chylomicron apoproteins (apoB, apoA-I) and utilized for indirect immunofluorescent localization of these apoproteins within rat intestinal epithelium during normal and impaired lipid absorption. Isolated intestinal epithelial cells prepared after different periods of lipid absorption from in situ intestinal segments revealed a rapid increase in fluorescence for both apoproteins that filled the entire apical portion of the cell. Prolonged lipid absorption for as long as 5 hr demonstrated sustained immunofluorescence and gave no indication of a depletion of the intestinal mucosa for either apoprotein during normal lipid absorption. [(3)H]Leucine incorporation into mesenteric lymph chylomicron apoproteins showed a linear decrease in specific activity of total chylomicron protein as well as apoB over 4 hr of a continuous lipid infusion indicating sustained active apoprotein synthesis during prolonged lipid absorption. Acetoxycloheximide, a potent inhibitor of protein synthesis, was employed to determine the dynamics of chylomicron apoproteins during an experimental condition of impaired lipid absorption. In animals with inhibited protein synthesis, fluorescence for both apoproteins was present early in the course of lipid absorption; however, at 60 min after the onset of lipid absorption, fluorescence for both apoproteins was absent. Fluorescence for both apoproteins returned during the recovery of protein synthesis. The present studies have confirmed previous results that localized two chylomicron apoproteins within intestinal epithelial cells. The present studies extend these observations and disclose a rapid and sustained synthesis of these apoproteins during prolonged chylomicron formation. During an experimental condition of impaired protein synthesis there was a marked reduction in the mucosal content of both apoA-I and apoB. These results are the first demonstration of impaired mucosal apoprotein synthesis during an experimental model of impaired lipid absorption."}
{"id": "PMID:204723", "title": "Pregnant mare serum gonadotrophin and follicle-stimulating hormone stimulation of cyclic AMP production in rat seminiferous tubule cells.", "content": "Pregnant mare serum gonadotrophin (PMSG) was found to stimulate the production of cyclic AMP in isolated rat seminiferous tubule cells. The PMSG was equipotent with highly purified ovine FSH. The subunits of PMSG were inactive in this system but recombination resulted in partial restoration of activity, and the combination of PMSG alpha-subunit with FSH beta-subunit was even more active. Desialation of PMSG, but not of ovine FSH, resulted in a reduction of slope and potency of this response, suggesting that sialic acid may be important for the interaction of PMSG and the Sertoli cell. Further tests of the responsiveness of this cell preparation demonstrated activity with several species of mammalian FSH molecules, but not with FSH molecules obtained from non-mammalian species.", "contents": "Pregnant mare serum gonadotrophin and follicle-stimulating hormone stimulation of cyclic AMP production in rat seminiferous tubule cells. Pregnant mare serum gonadotrophin (PMSG) was found to stimulate the production of cyclic AMP in isolated rat seminiferous tubule cells. The PMSG was equipotent with highly purified ovine FSH. The subunits of PMSG were inactive in this system but recombination resulted in partial restoration of activity, and the combination of PMSG alpha-subunit with FSH beta-subunit was even more active. Desialation of PMSG, but not of ovine FSH, resulted in a reduction of slope and potency of this response, suggesting that sialic acid may be important for the interaction of PMSG and the Sertoli cell. Further tests of the responsiveness of this cell preparation demonstrated activity with several species of mammalian FSH molecules, but not with FSH molecules obtained from non-mammalian species."}
{"id": "PMID:204724", "title": "Effect of progesterone on insulin secretion in the rat.", "content": "Implants of progesterone resulted in an increased amount of insulin in plasma in response to intravenous administration of glucose in the rat. Isolated islets of Langerhans from progesterone-treated animals showed a greater maximum secretory response to glucose than islets from control animals but their sensitivity to low concentrations of glucose was unchanged. Theophylline increased glucose-induced secretion of insulin to a greater extent in progesterone-treated than in control rats and also produced a greater increase in the concentration of cyclic AMP in isolated islets from hormone-treated animals. These results suggest that the effect of progesterone on insulin secretion may be mediated by a change in cyclic AMP levels in the beta cell. The possible role of progesterone in increasing the secretion of insulin in pregnancy is discussed.", "contents": "Effect of progesterone on insulin secretion in the rat. Implants of progesterone resulted in an increased amount of insulin in plasma in response to intravenous administration of glucose in the rat. Isolated islets of Langerhans from progesterone-treated animals showed a greater maximum secretory response to glucose than islets from control animals but their sensitivity to low concentrations of glucose was unchanged. Theophylline increased glucose-induced secretion of insulin to a greater extent in progesterone-treated than in control rats and also produced a greater increase in the concentration of cyclic AMP in isolated islets from hormone-treated animals. These results suggest that the effect of progesterone on insulin secretion may be mediated by a change in cyclic AMP levels in the beta cell. The possible role of progesterone in increasing the secretion of insulin in pregnancy is discussed."}
{"id": "PMID:204726", "title": "Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice I. Xenotropic virus.", "content": "The relationship between expression of xenotropic virus and the development of autoimmunization was studied in the progeny of crosses between New Zealand Black (NZB) and SWR mice. The (F1 X SWR) and F2 progeny segregated into three phenotypes: high-virus, low-virus, and virus-negative; F1 and (F1 X NZB) progeny were always high-virus. Autoantibodies, immune deposit nephritis and lymphomas developed in the progeny of these crosses. The virological phenotype of the animal could be dissociated from the presence of either autoantibodies or nephritis. For example, mice that expressed titers of virus as high as the NZB parent failed to develop signs of autoimmunization, even up to 24 mo of age. By contrast, some (F1 X SWR) and F2 mice that expressed low titers of virus developed autoimmune disease. Furthermore, a proportion of virus-negative mice produced autoantibodies and were found to have typical immune deposit nephritis. No viral antigens could be detected in the renal lesions of such virus-negative animals. By contrast with the dissociation between expression of virus and occurrence of nephritis, the presence of antibodies to DNA correlated with the development of renal lesions. We conclude that the genes that determine the expression of infectious xenotropic virus in NZB mice segregate independently from those that are involved in the autoimmune disease of these animals.", "contents": "Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice I. Xenotropic virus. The relationship between expression of xenotropic virus and the development of autoimmunization was studied in the progeny of crosses between New Zealand Black (NZB) and SWR mice. The (F1 X SWR) and F2 progeny segregated into three phenotypes: high-virus, low-virus, and virus-negative; F1 and (F1 X NZB) progeny were always high-virus. Autoantibodies, immune deposit nephritis and lymphomas developed in the progeny of these crosses. The virological phenotype of the animal could be dissociated from the presence of either autoantibodies or nephritis. For example, mice that expressed titers of virus as high as the NZB parent failed to develop signs of autoimmunization, even up to 24 mo of age. By contrast, some (F1 X SWR) and F2 mice that expressed low titers of virus developed autoimmune disease. Furthermore, a proportion of virus-negative mice produced autoantibodies and were found to have typical immune deposit nephritis. No viral antigens could be detected in the renal lesions of such virus-negative animals. By contrast with the dissociation between expression of virus and occurrence of nephritis, the presence of antibodies to DNA correlated with the development of renal lesions. We conclude that the genes that determine the expression of infectious xenotropic virus in NZB mice segregate independently from those that are involved in the autoimmune disease of these animals."}
{"id": "PMID:204727", "title": "Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice. II. The viral envelope glycoprotein gp70.", "content": "The retroviral envelope glycoprotein, gp70 was measured in the serum of New Zealand Black (NZB) and SWR mice and the progeny of their crosses. The serum gp70 values segregated to \"NZB-like\" and \"SWR-like\" levels in these mice. A complex mechanism determined the inheritance of NZB-like serum gp70 levels. We found that the factors determining the expression of this retroviral protein were independent of the genes (Nzv-1 and Nzv-2) that determined the expression of infectious xenotropic virus. Autoimmune disease, including immune deposit nephritis could be dissociated from the degree of expression of serum gp70. By contrast, presence of circulating immune complexes and anti-DNA antibody did correlate with the development of nephritis in these crosses. A significant correlation was found between high grade expression of serum gp70 and the presence of lymphomas in these mice.", "contents": "Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice. II. The viral envelope glycoprotein gp70. The retroviral envelope glycoprotein, gp70 was measured in the serum of New Zealand Black (NZB) and SWR mice and the progeny of their crosses. The serum gp70 values segregated to \"NZB-like\" and \"SWR-like\" levels in these mice. A complex mechanism determined the inheritance of NZB-like serum gp70 levels. We found that the factors determining the expression of this retroviral protein were independent of the genes (Nzv-1 and Nzv-2) that determined the expression of infectious xenotropic virus. Autoimmune disease, including immune deposit nephritis could be dissociated from the degree of expression of serum gp70. By contrast, presence of circulating immune complexes and anti-DNA antibody did correlate with the development of nephritis in these crosses. A significant correlation was found between high grade expression of serum gp70 and the presence of lymphomas in these mice."}
{"id": "PMID:204729", "title": "Interferon action III. The rate of primary transcription of vesicular stomatitis virus is inhibited by interferon action.", "content": "Transcription of vesicular stomatitis virus (VSV) in Vero cells was confined to the synthesis of parentally-derived mRNA (primary transcription) by the use of cycloheximide and/or a ts mutant, G41(IV), at a non-permissive temperature (40 degrees C). More transcripts accumulated in the presence of cycloheximide than in its absence. This so-called \"cycloheximide effect\" results from higher rates of virus transcription sustained for longer periods of time. The rate of VSV transcription initially increases linearly for 1 to 2 h after injection. Interferon reduces this rate (congruent to fourfold with 50 units/ml interferon) irrespective of the presence or absence of cycloheximide. The VSV mRNA transcripts synthesized in mock- or interferon-treated cells were equal in size and had an equivalent half-life of 17 h at 40 degrees C. It seems likely that once transcription is initiated in interferon-treated cells, it is completed successfully. Since interferon reduces the rate of early VSV primary transcript synthesis to below that achieved in the presence of cycloheximide, we conclude that interferon has an effect on transcription beyond that attributable solely to protein synthesis inhibition. We postulate that interferon decreases the probabiltiy of initiating virus transcription. Virus mRNA escaping this facet of interferon action may then encounter other facets such as post-transcriptional modification and/or inhibition of translation. However, the mandatory sequence of primary transcription leads to primary translation for negative-strand viruses like VSV dictates that the overall inhibitory effect of interferon on translation would derive in part from this prior inhibition of transcription. Thus, to apply the term \"primary effect\" to one particular facet of interferon action may not always be meaningful.", "contents": "Interferon action III. The rate of primary transcription of vesicular stomatitis virus is inhibited by interferon action. Transcription of vesicular stomatitis virus (VSV) in Vero cells was confined to the synthesis of parentally-derived mRNA (primary transcription) by the use of cycloheximide and/or a ts mutant, G41(IV), at a non-permissive temperature (40 degrees C). More transcripts accumulated in the presence of cycloheximide than in its absence. This so-called \"cycloheximide effect\" results from higher rates of virus transcription sustained for longer periods of time. The rate of VSV transcription initially increases linearly for 1 to 2 h after injection. Interferon reduces this rate (congruent to fourfold with 50 units/ml interferon) irrespective of the presence or absence of cycloheximide. The VSV mRNA transcripts synthesized in mock- or interferon-treated cells were equal in size and had an equivalent half-life of 17 h at 40 degrees C. It seems likely that once transcription is initiated in interferon-treated cells, it is completed successfully. Since interferon reduces the rate of early VSV primary transcript synthesis to below that achieved in the presence of cycloheximide, we conclude that interferon has an effect on transcription beyond that attributable solely to protein synthesis inhibition. We postulate that interferon decreases the probabiltiy of initiating virus transcription. Virus mRNA escaping this facet of interferon action may then encounter other facets such as post-transcriptional modification and/or inhibition of translation. However, the mandatory sequence of primary transcription leads to primary translation for negative-strand viruses like VSV dictates that the overall inhibitory effect of interferon on translation would derive in part from this prior inhibition of transcription. Thus, to apply the term \"primary effect\" to one particular facet of interferon action may not always be meaningful."}
{"id": "PMID:204730", "title": "Isolation of thioguanine resistant variants of K-BALB cells non-inducible for type C viruses by 5-iododeoxyuridine.", "content": "Cones of thioguanine resistant K-BALB mouse cells wereisolated which were inducible for endogenous type C virus synthesis by cycloheximide and dexamethsone, but not 5-iododeoxyuridine. A comparison of the number of foci formed on NRK and SC-I cells suggested that the xenotropic virus was suppressed. The variants were not defective in the incorporation of thymidine or iododeoxyuridine or deficient in thymidine kinase, but were deficient in hypoxanthine-guanine phosphoribosyltransferase and the incorporation of hypoxanthine into nucleic acid. Because these cells are blocked at some point in the expression of endogenous virus, they may prove useful in establishing the steps involved in chemical activation of virus synthesis.", "contents": "Isolation of thioguanine resistant variants of K-BALB cells non-inducible for type C viruses by 5-iododeoxyuridine. Cones of thioguanine resistant K-BALB mouse cells wereisolated which were inducible for endogenous type C virus synthesis by cycloheximide and dexamethsone, but not 5-iododeoxyuridine. A comparison of the number of foci formed on NRK and SC-I cells suggested that the xenotropic virus was suppressed. The variants were not defective in the incorporation of thymidine or iododeoxyuridine or deficient in thymidine kinase, but were deficient in hypoxanthine-guanine phosphoribosyltransferase and the incorporation of hypoxanthine into nucleic acid. Because these cells are blocked at some point in the expression of endogenous virus, they may prove useful in establishing the steps involved in chemical activation of virus synthesis."}
{"id": "PMID:204731", "title": "Reduction of intercellular adhesiveness of chick heart cells by herpes simplex viruses 1 and 2.", "content": "Infection with herpes simplex viruses type 1 or 2 prevented the aggregation of 7-day-old chick heart cells into smooth, spheroidal, spontaneously beating aggregates. Virus infection also caused a loosening of peripheral cells in aggregates formed from initially uninfected cells. Measurements of rate of attachment of labelled single heart cells to a monolayer of like cells (homotypic), to HEp-2 cells (heterotypic), or to plastic substrata (nonspecific adhesion) indicated that virus infection caused a significant but differential loss of homotypic and nonspecific adhesiveness, but no alteration in heterotypic attachment rates. These observations indicate that those cells surface changes induced by viruses which are related to cell adhesion can be quantified by techniques measuring attachment rates.", "contents": "Reduction of intercellular adhesiveness of chick heart cells by herpes simplex viruses 1 and 2. Infection with herpes simplex viruses type 1 or 2 prevented the aggregation of 7-day-old chick heart cells into smooth, spheroidal, spontaneously beating aggregates. Virus infection also caused a loosening of peripheral cells in aggregates formed from initially uninfected cells. Measurements of rate of attachment of labelled single heart cells to a monolayer of like cells (homotypic), to HEp-2 cells (heterotypic), or to plastic substrata (nonspecific adhesion) indicated that virus infection caused a significant but differential loss of homotypic and nonspecific adhesiveness, but no alteration in heterotypic attachment rates. These observations indicate that those cells surface changes induced by viruses which are related to cell adhesion can be quantified by techniques measuring attachment rates."}
{"id": "PMID:204732", "title": "Epstein-Barr (EB) virus genome-containing, EB nuclear antigen-negative B-lymphocyte populations in blood in acute infectious mononucleosis.", "content": "Experiments have been performed to identify the type and size of cell infected by EB virus in the blood of acute infectious mononucleosis (IM) patients, and to investigate the nature of the infection. Virus-infected cells, recognized by their ability to give rise to lymphoblastoid cell lines when co-cultivated with foetal lymphocytes, were shown to be restricted to the B-lymphocyte population. Samples of this population from each of eight IM patients were found to be negative for EB nuclear antigen (EBNA) staining. Thereafter, fractions of IM B-lymphocytes prepared on the basis of cell size were assayed either by co-cultivation, for the incidence of virus-infected cells, or by immunofluorescence staining for the presence of cells expressing EBNA. The great majority of virus-infected cells were found in the fractions of normal sized B-lymphocytes and yet these fractions were unequivocally EBNA-negative B-cell populations in IM blood is discussed in terms of the type of infection established by EB virus in the circulation of IM patients.", "contents": "Epstein-Barr (EB) virus genome-containing, EB nuclear antigen-negative B-lymphocyte populations in blood in acute infectious mononucleosis. Experiments have been performed to identify the type and size of cell infected by EB virus in the blood of acute infectious mononucleosis (IM) patients, and to investigate the nature of the infection. Virus-infected cells, recognized by their ability to give rise to lymphoblastoid cell lines when co-cultivated with foetal lymphocytes, were shown to be restricted to the B-lymphocyte population. Samples of this population from each of eight IM patients were found to be negative for EB nuclear antigen (EBNA) staining. Thereafter, fractions of IM B-lymphocytes prepared on the basis of cell size were assayed either by co-cultivation, for the incidence of virus-infected cells, or by immunofluorescence staining for the presence of cells expressing EBNA. The great majority of virus-infected cells were found in the fractions of normal sized B-lymphocytes and yet these fractions were unequivocally EBNA-negative B-cell populations in IM blood is discussed in terms of the type of infection established by EB virus in the circulation of IM patients."}
{"id": "PMID:204733", "title": "Mitogen induction of murine C-type viruses. IV. Effects of lipoprotein E. coli, pokeweed mitogen and dextran sulphate.", "content": "Lipoprotein E. coli, a B-cell mitogen, is identified as a new agent inducing the release of endogenous C-type virus from mouse spleen cells. Like lipopolysaccharide, a previously identified inducer, this compound has a synergistic effect with 5-bromo-2'-deoxyuridine. Induced virus has the characteristic density as well as morphology of C-type viruses. Budding viruses are detected on cultured BALB/c cells by electron microscopy 2 to 4 days following culturing in the presence of lipoprotein. Pokeweed mitogen, a compound mitogenic for T- and B-cells was negative when tested for virus induction, both alone and in combination with 5-bromo-2'-deoxyuridine. Dextran sulphate, another B-cell mitogen, was negative for induction as well. However, when, combined with lipopolysaccharide, it enhanced the virus release induced by this mitogen. In contrast, no additive effects were observed either by combining dextran sulphate with other virus amplifying mitogens or by combinations of mitogens which both have virus-inducing ability. This finding is discussed with respect to B-cell differentiation.", "contents": "Mitogen induction of murine C-type viruses. IV. Effects of lipoprotein E. coli, pokeweed mitogen and dextran sulphate. Lipoprotein E. coli, a B-cell mitogen, is identified as a new agent inducing the release of endogenous C-type virus from mouse spleen cells. Like lipopolysaccharide, a previously identified inducer, this compound has a synergistic effect with 5-bromo-2'-deoxyuridine. Induced virus has the characteristic density as well as morphology of C-type viruses. Budding viruses are detected on cultured BALB/c cells by electron microscopy 2 to 4 days following culturing in the presence of lipoprotein. Pokeweed mitogen, a compound mitogenic for T- and B-cells was negative when tested for virus induction, both alone and in combination with 5-bromo-2'-deoxyuridine. Dextran sulphate, another B-cell mitogen, was negative for induction as well. However, when, combined with lipopolysaccharide, it enhanced the virus release induced by this mitogen. In contrast, no additive effects were observed either by combining dextran sulphate with other virus amplifying mitogens or by combinations of mitogens which both have virus-inducing ability. This finding is discussed with respect to B-cell differentiation."}
{"id": "PMID:204734", "title": "Aggregation of enterovirus small plaque variants and polioviruses under low ionic strength conditions.", "content": "Virion aggregation in low ionic conditions was observed with small plaque variants of Coxsackievirus type B3 and Echovirus types 4 and 11 by sedimentation and filtration methods. Inclusion of salts or DEAE-dextran into the media prevented or reversed virion aggregation. The effect of pH on aggregate formation in low ionic strength solutions was also investigated with various strains of poliovirus. Type I Sabin strain formed aggregates even at high pH, while Mahoney strains did so only below pH 6.5. Type 2 virus, Sabin and MEF1 strains, and type 3 virus, Sabin, Saukett and Suwa strains, showed an intermediate behaviour between the two type 1 strains, except MEF1-LB strain, a clone obtained from MEF1 strain under acidic overlay, which showed little tendency to aggregate. These results were compared with the degree of the d character of the strains. Besides the effect of inhibiting virion aggregation, the inclusion of DEAE-dextran into a sucrose gradient slowed the sedimentation of some of the viruses in low ionic strength solutions.", "contents": "Aggregation of enterovirus small plaque variants and polioviruses under low ionic strength conditions. Virion aggregation in low ionic conditions was observed with small plaque variants of Coxsackievirus type B3 and Echovirus types 4 and 11 by sedimentation and filtration methods. Inclusion of salts or DEAE-dextran into the media prevented or reversed virion aggregation. The effect of pH on aggregate formation in low ionic strength solutions was also investigated with various strains of poliovirus. Type I Sabin strain formed aggregates even at high pH, while Mahoney strains did so only below pH 6.5. Type 2 virus, Sabin and MEF1 strains, and type 3 virus, Sabin, Saukett and Suwa strains, showed an intermediate behaviour between the two type 1 strains, except MEF1-LB strain, a clone obtained from MEF1 strain under acidic overlay, which showed little tendency to aggregate. These results were compared with the degree of the d character of the strains. Besides the effect of inhibiting virion aggregation, the inclusion of DEAE-dextran into a sucrose gradient slowed the sedimentation of some of the viruses in low ionic strength solutions."}
{"id": "PMID:204735", "title": "Involvement of microtubules in cytopathic effects of animal viruses: early proteins of adenovirus and herpesvirus inhibit formation of microtubular paracrystals in HeLa-S3 cells.", "content": "In order to examine the involvement of microtubules in the virus-induced cytopathic effect (c.p.e.), the effect of virus infection on the formation of microtubular paracrystals (PC) induced by 10 microgram/ml of vinblastine sulphate in HeLa-S3 cells was examined by phase-contrast microscopy. In poliovirus-infected cells, c.p.e. (cell rounding) and the inhibition of PC formation proceeded in parallel, starting 4 h post-infection. In Sendai virus-infected cells, however, PC formation was not inhibited even 24 h post-infection when most infected cells clearly showed c.p.e. (syncytial formation). In adenovirus-infected cells, the inhibition of PC formation was observed 9 h before the appearance of c.p.e. Cytosine arabinoside (ara C) did not block the inhibition of PC formation in infected cells, but blocked the appearance of late c.p.e. (nuclear alteration). Cycloheximide blocked both the inhibition of PC formation and the induction of late c.p.e. These results suggest that an early protein synthesized de novo by adenovirus is required for direct or indirect inhibition of the microtubular PC formation. Furthermore, on ultraviolet (u.v.) inactivation of adenovirus both activities (induction of early c.p.e. shown by shrinkage of cytoplasm, and inhibition of PC formation) followed the same inactivation curve and were inactivated at a slower rate than viral infectivity and the activity leading to late c.p.e. The u.v. light sensitive target responsible for the induction of early c.p.e. and the inhibition of PC formation is about 20% of that for infectivity and is in accord with the genome size of the early functioning virus genes. In herpes simplex virus (HSV)-infected cells, the inhibition of PC formation, the appearance of c.p.e. (cell rounding and disappearance of nucleoli) and the synthesis of V antigen proceeded in parallel. These three functions of HSV were not blocked in infected cells even when the de novo synthesis of virus DNA was inhibited by ara C or phosphonoacetic acid (PAA), whereas these three functions were blocked by cycloheximide, suggesting that a protein coded by the input virus genome early after infection inhibits the microtubular PC formation and is responsible for c.p.e. From the u.v. inactivation curve of HSV, it was confirmed that only one-tenth of virus genome was responsible for both activities (induction of c.p.e. and inhibition of PC formation).", "contents": "Involvement of microtubules in cytopathic effects of animal viruses: early proteins of adenovirus and herpesvirus inhibit formation of microtubular paracrystals in HeLa-S3 cells. In order to examine the involvement of microtubules in the virus-induced cytopathic effect (c.p.e.), the effect of virus infection on the formation of microtubular paracrystals (PC) induced by 10 microgram/ml of vinblastine sulphate in HeLa-S3 cells was examined by phase-contrast microscopy. In poliovirus-infected cells, c.p.e. (cell rounding) and the inhibition of PC formation proceeded in parallel, starting 4 h post-infection. In Sendai virus-infected cells, however, PC formation was not inhibited even 24 h post-infection when most infected cells clearly showed c.p.e. (syncytial formation). In adenovirus-infected cells, the inhibition of PC formation was observed 9 h before the appearance of c.p.e. Cytosine arabinoside (ara C) did not block the inhibition of PC formation in infected cells, but blocked the appearance of late c.p.e. (nuclear alteration). Cycloheximide blocked both the inhibition of PC formation and the induction of late c.p.e. These results suggest that an early protein synthesized de novo by adenovirus is required for direct or indirect inhibition of the microtubular PC formation. Furthermore, on ultraviolet (u.v.) inactivation of adenovirus both activities (induction of early c.p.e. shown by shrinkage of cytoplasm, and inhibition of PC formation) followed the same inactivation curve and were inactivated at a slower rate than viral infectivity and the activity leading to late c.p.e. The u.v. light sensitive target responsible for the induction of early c.p.e. and the inhibition of PC formation is about 20% of that for infectivity and is in accord with the genome size of the early functioning virus genes. In herpes simplex virus (HSV)-infected cells, the inhibition of PC formation, the appearance of c.p.e. (cell rounding and disappearance of nucleoli) and the synthesis of V antigen proceeded in parallel. These three functions of HSV were not blocked in infected cells even when the de novo synthesis of virus DNA was inhibited by ara C or phosphonoacetic acid (PAA), whereas these three functions were blocked by cycloheximide, suggesting that a protein coded by the input virus genome early after infection inhibits the microtubular PC formation and is responsible for c.p.e. From the u.v. inactivation curve of HSV, it was confirmed that only one-tenth of virus genome was responsible for both activities (induction of c.p.e. and inhibition of PC formation)."}
{"id": "PMID:204736", "title": "Isoelectric points of polypeptides of standard poliovirus particles of different serological types and of empty capsids and dense particles of poliovirus type 1.", "content": "The isoelectric points of polypeptides of standard and dense poliovirus particles and of empty capsids have been determined by isoelectric focusing in urea and by two-dimensional analysis. Comparing virus strains belonging to the three serological types of poliovirus, differences in the pI of some, but not all of the structural polypeptides are found. The pI of polypeptides of dense particles and of empty capsids are identical with those of standard particles. Polypeptide VPo present in empty capsids has a pI between those of VP4 and VP2.", "contents": "Isoelectric points of polypeptides of standard poliovirus particles of different serological types and of empty capsids and dense particles of poliovirus type 1. The isoelectric points of polypeptides of standard and dense poliovirus particles and of empty capsids have been determined by isoelectric focusing in urea and by two-dimensional analysis. Comparing virus strains belonging to the three serological types of poliovirus, differences in the pI of some, but not all of the structural polypeptides are found. The pI of polypeptides of dense particles and of empty capsids are identical with those of standard particles. Polypeptide VPo present in empty capsids has a pI between those of VP4 and VP2."}
{"id": "PMID:204737", "title": "Cytomegalovirus as a frequent cause of Guillain-Barr\u00e9 syndrome.", "content": "In 10 patients with Guillain-Barr\u00e9 syndrome a preceeding cytomegalovirus infection could be demonstrated by virus-specific IgM antibodies that were present in high titers in 9 of the 10 patients in the first serum specimen. The IgM antibodies to cytomegalovirus were detected by a sensitive \"double\" indirect immunofluorescence technique. In most of our cases (8 of 10) the complement-fixing antibody titers had already reached high levels on admission into a hospital, and significant titer changes were not observed. Cytomegalovirus was isolated from the urine of five patients.", "contents": "Cytomegalovirus as a frequent cause of Guillain-Barr\u00e9 syndrome. In 10 patients with Guillain-Barr\u00e9 syndrome a preceeding cytomegalovirus infection could be demonstrated by virus-specific IgM antibodies that were present in high titers in 9 of the 10 patients in the first serum specimen. The IgM antibodies to cytomegalovirus were detected by a sensitive \"double\" indirect immunofluorescence technique. In most of our cases (8 of 10) the complement-fixing antibody titers had already reached high levels on admission into a hospital, and significant titer changes were not observed. Cytomegalovirus was isolated from the urine of five patients."}
{"id": "PMID:204738", "title": "A study of the prevalence of rotavirus infection in children with gastroenteritis admitted to an infectious diseases hospital.", "content": "In a 12 month survey of infants and children with gastroenteritis admitted to Fairfield Hospital, Melbourne, rotavirus was found in approximately 42% of patients. This virus was detected more often during the winter months, particularly in children aged between 12 months and 3 years. Detection of rotavirus by electron microscopy was found to be more sensitive than by counterimmunoelectrophoresis. Routine bacterial and viral studies revealed that bacterial pathogens and common enteric viruses were associated with relatively few cases of gastroenteritis. There is little doubt that rotavirus is the most important aetiological agent of acute gastroenteritis in yvirus is the most important aetiological agent of acute gastroenteritis in young children in Melbourne.", "contents": "A study of the prevalence of rotavirus infection in children with gastroenteritis admitted to an infectious diseases hospital. In a 12 month survey of infants and children with gastroenteritis admitted to Fairfield Hospital, Melbourne, rotavirus was found in approximately 42% of patients. This virus was detected more often during the winter months, particularly in children aged between 12 months and 3 years. Detection of rotavirus by electron microscopy was found to be more sensitive than by counterimmunoelectrophoresis. Routine bacterial and viral studies revealed that bacterial pathogens and common enteric viruses were associated with relatively few cases of gastroenteritis. There is little doubt that rotavirus is the most important aetiological agent of acute gastroenteritis in yvirus is the most important aetiological agent of acute gastroenteritis in young children in Melbourne."}
{"id": "PMID:204739", "title": "Studies of an outbreak of acute hepatitis A: II. Antibody changes to cytomegalovirus and herpersvirus.", "content": "The acute and convalescent sera from 14 schoolchildren with acute hepatitis A were tested for antibody changes to 70 viral antigens. Marked decreases were noted in the levels of antibody to cytomegalovirus in 5 of the 14 children and in the levels of antibody to herpesvirus type 1 in 3. No such changes were noted in 9 sex- and age-matched healthy control children from the same classes.", "contents": "Studies of an outbreak of acute hepatitis A: II. Antibody changes to cytomegalovirus and herpersvirus. The acute and convalescent sera from 14 schoolchildren with acute hepatitis A were tested for antibody changes to 70 viral antigens. Marked decreases were noted in the levels of antibody to cytomegalovirus in 5 of the 14 children and in the levels of antibody to herpesvirus type 1 in 3. No such changes were noted in 9 sex- and age-matched healthy control children from the same classes."}
{"id": "PMID:204740", "title": "Seroepidemiological investigation of patients and family contacts in an epidemic of hepatitis A.", "content": "Serial blood and faecal samples were collected from patients and family contacts during an outbreak of hepatitis A in a village and tested by a solid-phase competitive type radioimmunoassay for hepatitis A antigen and hepatitis A antibody. The amount and duration of excretion of hepatitis A antigen was correlated with the severity of the illness. In 2 severe clinical cases, hepatitis A antigen was demonstrated in faecal extracts 11 days before the onset of jaundice and continuing for 10 days thereafter, with maximum shedding during the late incubation period. Faecal antigen was demonstrated in low concentrations for only 2 days in a patient with mild disease and in a person with subclinical infection. There was an inverse correlation between the incidence of infection and prevalence of hepatitis A antibody and age. Of 24 infections, 19 (79%) occurred in persons in the age group 0 to 20 years, a group in which only 6% of individuals had pre-existing antibody. Hepatitis A antibody was present in the serum of 3 persons in low titres of 1:20 to 1:40 on the day jaundice developed. The antibody titres increased very rapidly during the following 2 weeks of illness and slowly during the following months, reaching titres of 1:900 to 1:3500. In a separate study, a mean antibody titre of 1:591 was found in 13 patients, 12 years after clinical hepatitis A with jaundice.", "contents": "Seroepidemiological investigation of patients and family contacts in an epidemic of hepatitis A. Serial blood and faecal samples were collected from patients and family contacts during an outbreak of hepatitis A in a village and tested by a solid-phase competitive type radioimmunoassay for hepatitis A antigen and hepatitis A antibody. The amount and duration of excretion of hepatitis A antigen was correlated with the severity of the illness. In 2 severe clinical cases, hepatitis A antigen was demonstrated in faecal extracts 11 days before the onset of jaundice and continuing for 10 days thereafter, with maximum shedding during the late incubation period. Faecal antigen was demonstrated in low concentrations for only 2 days in a patient with mild disease and in a person with subclinical infection. There was an inverse correlation between the incidence of infection and prevalence of hepatitis A antibody and age. Of 24 infections, 19 (79%) occurred in persons in the age group 0 to 20 years, a group in which only 6% of individuals had pre-existing antibody. Hepatitis A antibody was present in the serum of 3 persons in low titres of 1:20 to 1:40 on the day jaundice developed. The antibody titres increased very rapidly during the following 2 weeks of illness and slowly during the following months, reaching titres of 1:900 to 1:3500. In a separate study, a mean antibody titre of 1:591 was found in 13 patients, 12 years after clinical hepatitis A with jaundice."}
{"id": "PMID:204741", "title": "Incidence and distribution of herpes simplex virus types 1 and 2 from genital lesions in college women.", "content": "During a 9-month period, 9,772 women were treated at the student health center's gynecology clinic. Herpes simplex virus was isolated from 30 of 57 patients clinically diagnosed as suffering from a herpetic or herpetic-like genial infection for a virological incidence rate of 0.31%. Using virus plaque diameter in chick embryo cells and heat stability of viral thymidine kinase, 37% of the isolates were classified as herpes simplex virus type 1 and 63% were classified as herpes simplex virus type 2.", "contents": "Incidence and distribution of herpes simplex virus types 1 and 2 from genital lesions in college women. During a 9-month period, 9,772 women were treated at the student health center's gynecology clinic. Herpes simplex virus was isolated from 30 of 57 patients clinically diagnosed as suffering from a herpetic or herpetic-like genial infection for a virological incidence rate of 0.31%. Using virus plaque diameter in chick embryo cells and heat stability of viral thymidine kinase, 37% of the isolates were classified as herpes simplex virus type 1 and 63% were classified as herpes simplex virus type 2."}
{"id": "PMID:204742", "title": "Immunotherapy of viral infections with transfer factor.", "content": "It has been reported that dialysable leucocyte extract preparations, thought to contain transfer factor, may be used therapeutically for the treatment of a variety of immunodeficiency syndromes. Clinical and laboratory studies have suggested that such preparations, in addition to transferring specific cellular immunity may also contain non-specific adjuvant activities. Attempts at immunotherapy of viral infections are described against a background of current research on the biological and biochemical properties of leucocyte dialysates.", "contents": "Immunotherapy of viral infections with transfer factor. It has been reported that dialysable leucocyte extract preparations, thought to contain transfer factor, may be used therapeutically for the treatment of a variety of immunodeficiency syndromes. Clinical and laboratory studies have suggested that such preparations, in addition to transferring specific cellular immunity may also contain non-specific adjuvant activities. Attempts at immunotherapy of viral infections are described against a background of current research on the biological and biochemical properties of leucocyte dialysates."}
{"id": "PMID:204743", "title": "Multiple buoyant densities of hepatitis A virus in cesium chloride gradients.", "content": "Hepatitis A virus (HAV) recovered from stools of human cases of hepatitis A and from stools of chimpanzees experimentally infected with HAV was shown to possess multiple buoyant densities in CsCl gradients. The greatest proportion of HAV was most frequently found at a buoyant density of 1.32-1.34 g/cm3, however, large proportions of HAV were also frequently found at higher densities, including 1.36-1.37, 1.40-1.42, and 1.45-1.48 g/cm3. These findings are consistent with the notion that HAV may be a parvovirus.", "contents": "Multiple buoyant densities of hepatitis A virus in cesium chloride gradients. Hepatitis A virus (HAV) recovered from stools of human cases of hepatitis A and from stools of chimpanzees experimentally infected with HAV was shown to possess multiple buoyant densities in CsCl gradients. The greatest proportion of HAV was most frequently found at a buoyant density of 1.32-1.34 g/cm3, however, large proportions of HAV were also frequently found at higher densities, including 1.36-1.37, 1.40-1.42, and 1.45-1.48 g/cm3. These findings are consistent with the notion that HAV may be a parvovirus."}
{"id": "PMID:204744", "title": "Picorna- and togavirus infection of cells detected by gas chromatography.", "content": "Viral infection of cells causes chemical and metabolic changes, which can be detected by gas chromatography (GC) of ether extracts of supernatant fluids and cell homogenates before any significant damage to the cells is observable microscopically. The characteristic and specific GC patterns obtained from BHK-21 and Vero cell cultures infected with encephalomyocarditis, polio, echoviruses, and a togavirus make it possible to distinguish between these infecting viruses. The appearance of 1 or 2 compounds, represented by GC peaks with TR values of 302 and 677 seconds seems to be specific for these viruses. Other peaks found in the supernatant media 1-2 hours after infection probably represent cell constituents leaking into the medium as a result of damage to the cell membrane by the invading virus.", "contents": "Picorna- and togavirus infection of cells detected by gas chromatography. Viral infection of cells causes chemical and metabolic changes, which can be detected by gas chromatography (GC) of ether extracts of supernatant fluids and cell homogenates before any significant damage to the cells is observable microscopically. The characteristic and specific GC patterns obtained from BHK-21 and Vero cell cultures infected with encephalomyocarditis, polio, echoviruses, and a togavirus make it possible to distinguish between these infecting viruses. The appearance of 1 or 2 compounds, represented by GC peaks with TR values of 302 and 677 seconds seems to be specific for these viruses. Other peaks found in the supernatant media 1-2 hours after infection probably represent cell constituents leaking into the medium as a result of damage to the cell membrane by the invading virus."}
{"id": "PMID:204745", "title": "Peripheral neuropathy and solitary plasmacytoma.", "content": "Three patients with peripheral neuropathy and a solitary plasmacytoma are presented, and the literature is reviewed. It is suggested that middle-aged men with an obscure progressive sensorimotor neuropathy, a raised CSF protein, and otherwise negative investigations should have a full skeletal survey since irradiation of a plasmacytoma may lead to a considerable improvement in the associated neurological disability.", "contents": "Peripheral neuropathy and solitary plasmacytoma. Three patients with peripheral neuropathy and a solitary plasmacytoma are presented, and the literature is reviewed. It is suggested that middle-aged men with an obscure progressive sensorimotor neuropathy, a raised CSF protein, and otherwise negative investigations should have a full skeletal survey since irradiation of a plasmacytoma may lead to a considerable improvement in the associated neurological disability."}
{"id": "PMID:204746", "title": "Neuromuscular transmission in human single motor units.", "content": "A method, multiple point stimulation, has been reported to isolate 5-20 single hypothenar or thenar motor units for investigation. This method is attractive for testing neuromuscular transmission because the required stimulus intensities are much less than for supramaximal nerve stimulation, and movement artefact is less of a problem. In this investigation of controls, the changes in hypothenar and thenar motor unit surface voltage and latency of single muscle fibre action potentials belonging to the motor unit have been measured in response to trains of stimuli delivered to the motor nerve. In healthy motor units, increases in the surface peak-to-peak voltage and corresponding reductions in the peak-to-peak duration occurred, the changes being maximum at the shorter stimulus intervals and accompanied by increased synchronisation of motor unit muscle fibre action potential discharges. The investigations of the responses for healthy single motor units to repetitive stimulation provide the basis for investigations of neuromuscular transmission at the level of the motor unit in diseases of neuromuscular transmission.", "contents": "Neuromuscular transmission in human single motor units. A method, multiple point stimulation, has been reported to isolate 5-20 single hypothenar or thenar motor units for investigation. This method is attractive for testing neuromuscular transmission because the required stimulus intensities are much less than for supramaximal nerve stimulation, and movement artefact is less of a problem. In this investigation of controls, the changes in hypothenar and thenar motor unit surface voltage and latency of single muscle fibre action potentials belonging to the motor unit have been measured in response to trains of stimuli delivered to the motor nerve. In healthy motor units, increases in the surface peak-to-peak voltage and corresponding reductions in the peak-to-peak duration occurred, the changes being maximum at the shorter stimulus intervals and accompanied by increased synchronisation of motor unit muscle fibre action potential discharges. The investigations of the responses for healthy single motor units to repetitive stimulation provide the basis for investigations of neuromuscular transmission at the level of the motor unit in diseases of neuromuscular transmission."}
{"id": "PMID:204747", "title": "Neuromuscular transmission in myasthenic single motor units.", "content": "In patients with myasthenia gravis neuromuscular transmission has been tested in individual hypothenar and thenar motor units using trains of near threshold electrical stimuli delivered to the motor nerve. The most important observations included: (1) the proportion of motor units with pathological decrements varied from 0 to 90%, (2) the decrements in surface voltage were frequently much more normal in individual motor units than in the corresponding maximum compound potentials evoked by supramaximal nerve stimulation, and (3) the most abnormal decrements were observed in motor units at the low end of the surface voltage range. These observations can be interpreted to suggest important neurogenic factors in the pathogenesis of myasthenia gravis. An attractive alternative would be to suggest that the small motor units have the most abnormal neuromuscular transmission because they normally have a lower margin for safe neuromuscular transmission and, as a consequence, fail first in diseases of neuromuscular transmission.", "contents": "Neuromuscular transmission in myasthenic single motor units. In patients with myasthenia gravis neuromuscular transmission has been tested in individual hypothenar and thenar motor units using trains of near threshold electrical stimuli delivered to the motor nerve. The most important observations included: (1) the proportion of motor units with pathological decrements varied from 0 to 90%, (2) the decrements in surface voltage were frequently much more normal in individual motor units than in the corresponding maximum compound potentials evoked by supramaximal nerve stimulation, and (3) the most abnormal decrements were observed in motor units at the low end of the surface voltage range. These observations can be interpreted to suggest important neurogenic factors in the pathogenesis of myasthenia gravis. An attractive alternative would be to suggest that the small motor units have the most abnormal neuromuscular transmission because they normally have a lower margin for safe neuromuscular transmission and, as a consequence, fail first in diseases of neuromuscular transmission."}
{"id": "PMID:204748", "title": "Peripheral neuropathy and benign IgG paraproteinaemia.", "content": "Three patients with peripheral neuropathy and an associated benign IgG paraproteinaemia are described. No direct immunological evidence for an aetiological role of the paraprotein was found, and the implications of this are discussed.", "contents": "Peripheral neuropathy and benign IgG paraproteinaemia. Three patients with peripheral neuropathy and an associated benign IgG paraproteinaemia are described. No direct immunological evidence for an aetiological role of the paraprotein was found, and the implications of this are discussed."}
{"id": "PMID:204749", "title": "Electronystagmographic criteria in neuro-otological diagnosis. 1. Peripheral lesions.", "content": "Direct current electronystagmographic recordings of spontaneous nystagmus, in the light, in darkness, and with eye closure were carried out on 34 patients with peripheral lesions of the vestibular system with a view to determining their specificity. In 60% of patients the responses were characterised by an enhancement of the nystagmus both with eye closure and in darkness. The remainder exhibited no nystagmus under any recording condition.", "contents": "Electronystagmographic criteria in neuro-otological diagnosis. 1. Peripheral lesions. Direct current electronystagmographic recordings of spontaneous nystagmus, in the light, in darkness, and with eye closure were carried out on 34 patients with peripheral lesions of the vestibular system with a view to determining their specificity. In 60% of patients the responses were characterised by an enhancement of the nystagmus both with eye closure and in darkness. The remainder exhibited no nystagmus under any recording condition."}
{"id": "PMID:204750", "title": "[Peripheral neuropathy with cryoglobulinemia (author's transl)].", "content": "The author describe 2 personal observations of peripheral neuropathy with cryoglobulinemia and the 28 cases previously recorded are reviewed. The characteristics of the usually sensorimotor neuropathy are not specific. Nevertheless, the association with purpura, Raynaud's syndrome and leg ulcers and the inconstant aggravation of the symptoms with cold allow the diagnosis to be suspected on clinical grounds. Cryoglobulin can be recognised by immunoelectrophoresis and classified as type I monoclonal, types II and III mixed and polyclonal. Associated disease should be looked for; lymphocytic proliferation or auto-immune disease. If none is found a diagnosis of essential cryoglobulinemia can be made but with caution as cryoglobulinemia can precede by several years the appearance of associated disease.", "contents": "[Peripheral neuropathy with cryoglobulinemia (author's transl)]. The author describe 2 personal observations of peripheral neuropathy with cryoglobulinemia and the 28 cases previously recorded are reviewed. The characteristics of the usually sensorimotor neuropathy are not specific. Nevertheless, the association with purpura, Raynaud's syndrome and leg ulcers and the inconstant aggravation of the symptoms with cold allow the diagnosis to be suspected on clinical grounds. Cryoglobulin can be recognised by immunoelectrophoresis and classified as type I monoclonal, types II and III mixed and polyclonal. Associated disease should be looked for; lymphocytic proliferation or auto-immune disease. If none is found a diagnosis of essential cryoglobulinemia can be made but with caution as cryoglobulinemia can precede by several years the appearance of associated disease."}
{"id": "PMID:204751", "title": "Moebius syndrome, peripheral neuropathy and hypogonadotrophic hypogonadism.", "content": "The association of congenital ophthalmoplegia and facial paresis (Moebius syndrome) with a variety of other developmental somatic defects has been widely recognised. Its co-existence with hypogonadism of hypothalamic/pituitary origin and subclinical peripheral neuropathy has been reported and in this paper we describe the second case of the Moebius syndrome in association with hypogonadotrophic hypogonadism and a progressive peripheral neuropathy of mixed axonal and demyelinating type.", "contents": "Moebius syndrome, peripheral neuropathy and hypogonadotrophic hypogonadism. The association of congenital ophthalmoplegia and facial paresis (Moebius syndrome) with a variety of other developmental somatic defects has been widely recognised. Its co-existence with hypogonadism of hypothalamic/pituitary origin and subclinical peripheral neuropathy has been reported and in this paper we describe the second case of the Moebius syndrome in association with hypogonadotrophic hypogonadism and a progressive peripheral neuropathy of mixed axonal and demyelinating type."}
{"id": "PMID:204752", "title": "How do axons control myelin formation? The model of 6-aminonicotinamide neuropathy.", "content": "Injection of 6-aminonicotinamide into young rats produces a peculiar neuropathy characterized by selective swelling and disruption of the layer of Schwann cell cytoplasm lining the inner surface of the myelin sheath. This layer increases greatly in volume, compressing the axon and distending the myelin sheath. Morphometry of such swollen fibers discloses that the amount of myelin in the distended sheaths is considerably greater than would correspond to the size of the axons, even if axonal compression is accounted for. The data favor the concept that sheath growth is stimulated by non-specific distension of the myelin sheath from inside.", "contents": "How do axons control myelin formation? The model of 6-aminonicotinamide neuropathy. Injection of 6-aminonicotinamide into young rats produces a peculiar neuropathy characterized by selective swelling and disruption of the layer of Schwann cell cytoplasm lining the inner surface of the myelin sheath. This layer increases greatly in volume, compressing the axon and distending the myelin sheath. Morphometry of such swollen fibers discloses that the amount of myelin in the distended sheaths is considerably greater than would correspond to the size of the axons, even if axonal compression is accounted for. The data favor the concept that sheath growth is stimulated by non-specific distension of the myelin sheath from inside."}
{"id": "PMID:204755", "title": "Fatty acid accumulation and abnormal lipid deposition in peripheral and border zones of experimental myocardial infarcts.", "content": "Twenty-eight dogs with acute anterior myocardial infarcts due to proximal occlusion of the left anterior descending coronary artery (LAD) were studied at various periods following the occlusion to determine: (a) the time course and location of abnormal lipid accumulation after infarction, (b) the degree of muscle-cell injury associated with increased lipid deposition, and (c) whether uptake of fatty acid from the circulating fat pool contributes to lipid accumulation in certain myocardial regions. The findings show that myocardial lipid accumulation begins as early as 6 hr after proximal LAD occulsion. The increased lipid deposition occurs as nonmembrane-bound lipid droplets in muscle cells with and without ultrastructural evidence of irreversible injury. Analysis of tissue uptake of intravenoulsy injected [14C] oleic acid conjugated with albumin revealed relatively selective concentration of label in the peripheral and border regions of the infarct, but occasionally even the central subendocardial portion of the infarct concentrated the fatty acid. Thin-layer chromotography showed that most of the label was associated with the triglyceride fraction when the radiolabeled fatty acid was injected 6 or 24 hr after LAD occlusion. These myocardial cellular and topographical alterations will have to be considered when labeled fatty acids are used for imaging acute myocardial infarcts and/or if attempts are made to identify myocardial fat-laden cells scintigraphically.", "contents": "Fatty acid accumulation and abnormal lipid deposition in peripheral and border zones of experimental myocardial infarcts. Twenty-eight dogs with acute anterior myocardial infarcts due to proximal occlusion of the left anterior descending coronary artery (LAD) were studied at various periods following the occlusion to determine: (a) the time course and location of abnormal lipid accumulation after infarction, (b) the degree of muscle-cell injury associated with increased lipid deposition, and (c) whether uptake of fatty acid from the circulating fat pool contributes to lipid accumulation in certain myocardial regions. The findings show that myocardial lipid accumulation begins as early as 6 hr after proximal LAD occulsion. The increased lipid deposition occurs as nonmembrane-bound lipid droplets in muscle cells with and without ultrastructural evidence of irreversible injury. Analysis of tissue uptake of intravenoulsy injected [14C] oleic acid conjugated with albumin revealed relatively selective concentration of label in the peripheral and border regions of the infarct, but occasionally even the central subendocardial portion of the infarct concentrated the fatty acid. Thin-layer chromotography showed that most of the label was associated with the triglyceride fraction when the radiolabeled fatty acid was injected 6 or 24 hr after LAD occlusion. These myocardial cellular and topographical alterations will have to be considered when labeled fatty acids are used for imaging acute myocardial infarcts and/or if attempts are made to identify myocardial fat-laden cells scintigraphically."}
{"id": "PMID:204756", "title": "Tc-99m pyrophosphate muscle labeling in McArdle syndrome.", "content": "This paper reports the findings on two patients with McArdle syndrome (myophosphorylase deficiency) in whom conventional bone scans with Tc-99m pyrophosphate revealed intense muscle labeling following exercise tests. The temporal pattern observed was similar to that seen with other types of muscle damage. The prolonged cramps often occurring with this entity appears to produce muscle damage that is readily demonstrable using conventional bone-scanning techniques.", "contents": "Tc-99m pyrophosphate muscle labeling in McArdle syndrome. This paper reports the findings on two patients with McArdle syndrome (myophosphorylase deficiency) in whom conventional bone scans with Tc-99m pyrophosphate revealed intense muscle labeling following exercise tests. The temporal pattern observed was similar to that seen with other types of muscle damage. The prolonged cramps often occurring with this entity appears to produce muscle damage that is readily demonstrable using conventional bone-scanning techniques."}
{"id": "PMID:204758", "title": "Scintigraphic abnormalities in glycogen storage disease.", "content": "Fifteen patients with glycogen-storage disease type 1 (von Gierke's disease) were evaluated by serial scintigraphy, with a clearly recognizable pattern of an enlarged liver with diminished radionuclide accumulation, splenomegaly with considerably increased uptake and renomegaly. In seven of these patients with GSD-1 scintigraphy demonstrated focal defects of varying size. Small or stable defects suggest benign hepatic adenomata, whereas malignant change occurred in growing large lesions. The potential malignant end-point of hepatic-cell carcinoma in GSD-1 warrants careful serial liver scintigraphy with scintiangiography on a routine basis.", "contents": "Scintigraphic abnormalities in glycogen storage disease. Fifteen patients with glycogen-storage disease type 1 (von Gierke's disease) were evaluated by serial scintigraphy, with a clearly recognizable pattern of an enlarged liver with diminished radionuclide accumulation, splenomegaly with considerably increased uptake and renomegaly. In seven of these patients with GSD-1 scintigraphy demonstrated focal defects of varying size. Small or stable defects suggest benign hepatic adenomata, whereas malignant change occurred in growing large lesions. The potential malignant end-point of hepatic-cell carcinoma in GSD-1 warrants careful serial liver scintigraphy with scintiangiography on a routine basis."}
{"id": "PMID:204760", "title": "Enteroviral disease in early infancy.", "content": "To discover the nature of enteroviral infections in early infancy (infants less than two months of age) in the United States, data were examined of 338 such infants with nonpolio enterovirus isolates reported to the Center for Disease Control in 1972-1975. Interpretation of such data is limited by reporting bias and difficulty in documenting disease causality. Enteroviral disease was severe in 74% of the infants. The most common clinical manifestations were meningitis, severe systemic disease, nonspecific febrile illness, and gastrointestinal symptoms. Fifty-one percent of all enteroviral disease was associated with echoviruses; 45% with Coxsackie B viruses; and only 4% with Coxsackie A viruses. Disease was more prevalent in the summer months, was recognized throughout the country, and occurred more frequently in males.", "contents": "Enteroviral disease in early infancy. To discover the nature of enteroviral infections in early infancy (infants less than two months of age) in the United States, data were examined of 338 such infants with nonpolio enterovirus isolates reported to the Center for Disease Control in 1972-1975. Interpretation of such data is limited by reporting bias and difficulty in documenting disease causality. Enteroviral disease was severe in 74% of the infants. The most common clinical manifestations were meningitis, severe systemic disease, nonspecific febrile illness, and gastrointestinal symptoms. Fifty-one percent of all enteroviral disease was associated with echoviruses; 45% with Coxsackie B viruses; and only 4% with Coxsackie A viruses. Disease was more prevalent in the summer months, was recognized throughout the country, and occurred more frequently in males."}
{"id": "PMID:204764", "title": "Archenteronoma (yolk sac tumors).", "content": "Ten cases of archenteronoma are reviewed with a follow-up between 2 mo and 7 yr. Their presentation was similar to that of rhabdomyosarcoma except for testicular tumors that may present as a hydrocele. A good prognosis was found with tumors amenable to primary resection and chemotherapy. Other tumors are best treated initially with chemotherapy before relatively conservative surgery, radiotherapy being used either pre- or postoperatively.", "contents": "Archenteronoma (yolk sac tumors). Ten cases of archenteronoma are reviewed with a follow-up between 2 mo and 7 yr. Their presentation was similar to that of rhabdomyosarcoma except for testicular tumors that may present as a hydrocele. A good prognosis was found with tumors amenable to primary resection and chemotherapy. Other tumors are best treated initially with chemotherapy before relatively conservative surgery, radiotherapy being used either pre- or postoperatively."}
{"id": "PMID:204766", "title": "Behavioral and electrophysiological effects of peptides related to lipotropin (beta-LPH).", "content": "Both C-terminal fragments of lipotropin (beta-LPH) (endorphins) and N-terminal fragments (e.g., ACTH 4-10) delayed extinction of pole-jumping avoidance behavior in rats. After subcutaneous injection Met5-enkephalin appeared to be as active as ACTH 4-10 whereas beta-LPH 61-69, alpha- and beta-endorphin were more potent in delaying extinction  of pole-jumping avoidance behavior (approximate ED50 of alpha-endorphin 4 x 10(-11) M rat.) However, the potency of beta-LPH 61-69 and alpha-endorphin appeared to be approximately the same whereas that of beta-endorphin was less than that of ACTH 4-10 after intraventricular administration (approximate ED50 of alpha-endorphin 0.2 x 10(-11) M rat). alpha-Endorphin and ACTH 4-10, administered subcutaneously in a dose which markedly delayed extinction of pole-jumping avoidance behavior, had only slight effects on open field behavior and on responsiveness to electric footshock. A 5 times higher dose of both peptides facilitated passive avoidance behavior. Morphine in two doses significantly delayed extinction of pole-jumping avoidance behavior but the effect was not dose dependent. The specific opiate antagonist naltrexone, however, markedly facilitated extinction of the avoidance response. ACTH 4-10, alpha- and beta-endorphin and a behaviorally potent ACTH 4-9 analog (Org 2766) restored pole-jumping avoidance behavior of rats pretreated with naltrexone. Treatment with a similar dose of naltrexone blocked beta-endorphin-induced analgesia. These results suggest that the influence of peptides related to C-terminal and N-terminal fragments of lipotropin on extinction of avoidance behavior may be dissociated from those exerted on opiate receptor sites. Subcutaneously injected beta-LPH 61-69 or intraventricularly administered beta-endorphin induced a shift from lower to higher frequencies of hippocampal theta rhythm during paradoxical sleep in the same way as that found after ACTH 4-10. This effect is interpreted as indicating an increased arousal state in certain midbrain limbic structures. This may, as has been postulated for ACTH 4-10, alter the motivational value of environmental stimuli (e.g., aversive stimulation).", "contents": "Behavioral and electrophysiological effects of peptides related to lipotropin (beta-LPH). Both C-terminal fragments of lipotropin (beta-LPH) (endorphins) and N-terminal fragments (e.g., ACTH 4-10) delayed extinction of pole-jumping avoidance behavior in rats. After subcutaneous injection Met5-enkephalin appeared to be as active as ACTH 4-10 whereas beta-LPH 61-69, alpha- and beta-endorphin were more potent in delaying extinction  of pole-jumping avoidance behavior (approximate ED50 of alpha-endorphin 4 x 10(-11) M rat.) However, the potency of beta-LPH 61-69 and alpha-endorphin appeared to be approximately the same whereas that of beta-endorphin was less than that of ACTH 4-10 after intraventricular administration (approximate ED50 of alpha-endorphin 0.2 x 10(-11) M rat). alpha-Endorphin and ACTH 4-10, administered subcutaneously in a dose which markedly delayed extinction of pole-jumping avoidance behavior, had only slight effects on open field behavior and on responsiveness to electric footshock. A 5 times higher dose of both peptides facilitated passive avoidance behavior. Morphine in two doses significantly delayed extinction of pole-jumping avoidance behavior but the effect was not dose dependent. The specific opiate antagonist naltrexone, however, markedly facilitated extinction of the avoidance response. ACTH 4-10, alpha- and beta-endorphin and a behaviorally potent ACTH 4-9 analog (Org 2766) restored pole-jumping avoidance behavior of rats pretreated with naltrexone. Treatment with a similar dose of naltrexone blocked beta-endorphin-induced analgesia. These results suggest that the influence of peptides related to C-terminal and N-terminal fragments of lipotropin on extinction of avoidance behavior may be dissociated from those exerted on opiate receptor sites. Subcutaneously injected beta-LPH 61-69 or intraventricularly administered beta-endorphin induced a shift from lower to higher frequencies of hippocampal theta rhythm during paradoxical sleep in the same way as that found after ACTH 4-10. This effect is interpreted as indicating an increased arousal state in certain midbrain limbic structures. This may, as has been postulated for ACTH 4-10, alter the motivational value of environmental stimuli (e.g., aversive stimulation)."}
{"id": "PMID:204767", "title": "Purine nucleoside and nucleotide interactions on normal and subsensitive alpha adrenoreceptor responsiveness in guinea-pig vas deferens.", "content": "Adenosine and adenosine 5'-monophosphate (AMP) augment contractile responses to norepinephrine (NE) in isolated guinea-pig vas deferens. Dipyridamole slightly enhances, while theophylline antagonizes, adenosine effects on responses to NE. Adenosine triphosphate (ATP) and the nonhydrolyzable analog, adenosine 5'-(beta,gamma-imido)triphosphate (AppNp) depress responses to NE. Adenine and adenosine diphosphate (ADP) are ineffective in influencing alpha adrenoreceptor responsiveness. Repetitive stimulation of isolated vas deferens with maximal concentrations of NE markedly reduce the contractile response to test concentrations of 6 micron NE. Spontaneous resensitization of responses to NE to control levels occurs within 25 to 35 minutes after the end of desensitization treatment. Adenine nucleosides and nucleotides promote a more rapid rate of alpha adrenoreceptor resensitization, with a potency order: AMP greater than adenosine greater than ADP. Adenine and ATP did not influence the rate of alpha adrenoreceptor resensitization. The adenine nucleotides ADP, ATP and the analog AppNp elicit concentration-dependent contractions of guinea-pig vas deferens. Theophylline antagonizes this contractile activity to adenine nucleotides. AMP, adenosine and adenine are devoid of agonistic activity. In the presence of NE, however, AMP and adenosine produce contractile responses of isolated vas deferens strips, and the agonistic activity of ADP, ATP and AppNp is profoundly enhanced. Agonistic actions of purines in the presence of NE are antagonized by phentolamine much more effectively than by theophylline. The results suggest the existence of a purinergic receptor mediating excitatory responses of guinea-pig vas deferens. Furthermore, there appears to be mutual interaction between purinergic and alpha adrenoreceptor mechanisms. That adenyl derivatives are capable of augmenting subsensitive alpha adrenoreceptor responsiveness suggests that adenine nucleosides or nucleotides, released during sympathetic transmission, may be required for maintenance of normal alpha adrenoreceptor sensitivity.", "contents": "Purine nucleoside and nucleotide interactions on normal and subsensitive alpha adrenoreceptor responsiveness in guinea-pig vas deferens. Adenosine and adenosine 5'-monophosphate (AMP) augment contractile responses to norepinephrine (NE) in isolated guinea-pig vas deferens. Dipyridamole slightly enhances, while theophylline antagonizes, adenosine effects on responses to NE. Adenosine triphosphate (ATP) and the nonhydrolyzable analog, adenosine 5'-(beta,gamma-imido)triphosphate (AppNp) depress responses to NE. Adenine and adenosine diphosphate (ADP) are ineffective in influencing alpha adrenoreceptor responsiveness. Repetitive stimulation of isolated vas deferens with maximal concentrations of NE markedly reduce the contractile response to test concentrations of 6 micron NE. Spontaneous resensitization of responses to NE to control levels occurs within 25 to 35 minutes after the end of desensitization treatment. Adenine nucleosides and nucleotides promote a more rapid rate of alpha adrenoreceptor resensitization, with a potency order: AMP greater than adenosine greater than ADP. Adenine and ATP did not influence the rate of alpha adrenoreceptor resensitization. The adenine nucleotides ADP, ATP and the analog AppNp elicit concentration-dependent contractions of guinea-pig vas deferens. Theophylline antagonizes this contractile activity to adenine nucleotides. AMP, adenosine and adenine are devoid of agonistic activity. In the presence of NE, however, AMP and adenosine produce contractile responses of isolated vas deferens strips, and the agonistic activity of ADP, ATP and AppNp is profoundly enhanced. Agonistic actions of purines in the presence of NE are antagonized by phentolamine much more effectively than by theophylline. The results suggest the existence of a purinergic receptor mediating excitatory responses of guinea-pig vas deferens. Furthermore, there appears to be mutual interaction between purinergic and alpha adrenoreceptor mechanisms. That adenyl derivatives are capable of augmenting subsensitive alpha adrenoreceptor responsiveness suggests that adenine nucleosides or nucleotides, released during sympathetic transmission, may be required for maintenance of normal alpha adrenoreceptor sensitivity."}
{"id": "PMID:204768", "title": "Epinephrine-induced automaticity of canine cardiac Purkinje fibers and its relationship to the adenylate cyclase-adenosine 3',5'-monophosphate system.", "content": "We studied the relationship between epinephrine-induced increases in automaticity and in the adenylate cyclase-adenosine 3',5'-monophosphate (cAMP) system in canine cardiac Purkinje fibers. In intact Purkinje fiber bundles superfused with Tyrode's solution, epinephrine induced a concentration-dependent increase in automaticity and in cAMP content. Both of these effects were reduced by propranolol. Decreasing the temperature of the superfusate from 37 degrees to 25 degrees C blocked the epinephrine-induced increase in automaticity, but not the increase in cAMP content. Addition of the metabolic blocking agent, iodoacetate, to the superfusate did not block the effect on Purkinje fiber automaticity, but the cAMP content did not increase. In Purkinje fiber bundle whole homogenates adenylate cyclase was stimulated more by isoproterenol than by epinephrine. Low concentrations of phenylephrine decreased adenylate cyclase activity; higher concentrations induced an increase toward control values. Iodoacetate did not significantly alter cyclase activity and did not affect its response to epinephrine. These students have shown that although intact Purkinje fiber bundles respond to epinephrine with increases in automaticity and cAMP content, these two events can be dissociated under appropriate conditions.", "contents": "Epinephrine-induced automaticity of canine cardiac Purkinje fibers and its relationship to the adenylate cyclase-adenosine 3',5'-monophosphate system. We studied the relationship between epinephrine-induced increases in automaticity and in the adenylate cyclase-adenosine 3',5'-monophosphate (cAMP) system in canine cardiac Purkinje fibers. In intact Purkinje fiber bundles superfused with Tyrode's solution, epinephrine induced a concentration-dependent increase in automaticity and in cAMP content. Both of these effects were reduced by propranolol. Decreasing the temperature of the superfusate from 37 degrees to 25 degrees C blocked the epinephrine-induced increase in automaticity, but not the increase in cAMP content. Addition of the metabolic blocking agent, iodoacetate, to the superfusate did not block the effect on Purkinje fiber automaticity, but the cAMP content did not increase. In Purkinje fiber bundle whole homogenates adenylate cyclase was stimulated more by isoproterenol than by epinephrine. Low concentrations of phenylephrine decreased adenylate cyclase activity; higher concentrations induced an increase toward control values. Iodoacetate did not significantly alter cyclase activity and did not affect its response to epinephrine. These students have shown that although intact Purkinje fiber bundles respond to epinephrine with increases in automaticity and cAMP content, these two events can be dissociated under appropriate conditions."}
{"id": "PMID:204769", "title": "Position sensitivity of de-efferented muscle spindles in experimental acrylamide neuropathy.", "content": "An experimental neuropathy was induced in cats by injections of acrylamide (7.5, 15 or 30 mg/kg/day) for 2 to 10 days. The responses of primary and secondary endings of soleus muscle spindles to stretch were evaluated and correlated with the appearance of ataxia and incoordinated motor movements. Animals that received 15 or 30 mg/kg/day became ataxic and demonstrated poor motor coordination on the 7th or 4th day, respectively. At these times, both primary and secondary endings of muscle spindles had elevated thresholds and diminished discharge frequencies. Continued acrylamide administration resulted in exacerbation of the clinical symptoms and further attenuation of spindle responses. The discontinuation of acrylamide was followed by slow recovery. Only those cats which received a total dose of 75 mg/kg or less remained asymptomatic and had normal spindle function. The coincidence of onset of motor coordination deficits and spindle dysfunction, coupled with a lack of demonstrable motor defect at the same time, suggests that the initial clinical features of acrylamide neuropathy may be partly the consequence of impaired spindle function.", "contents": "Position sensitivity of de-efferented muscle spindles in experimental acrylamide neuropathy. An experimental neuropathy was induced in cats by injections of acrylamide (7.5, 15 or 30 mg/kg/day) for 2 to 10 days. The responses of primary and secondary endings of soleus muscle spindles to stretch were evaluated and correlated with the appearance of ataxia and incoordinated motor movements. Animals that received 15 or 30 mg/kg/day became ataxic and demonstrated poor motor coordination on the 7th or 4th day, respectively. At these times, both primary and secondary endings of muscle spindles had elevated thresholds and diminished discharge frequencies. Continued acrylamide administration resulted in exacerbation of the clinical symptoms and further attenuation of spindle responses. The discontinuation of acrylamide was followed by slow recovery. Only those cats which received a total dose of 75 mg/kg or less remained asymptomatic and had normal spindle function. The coincidence of onset of motor coordination deficits and spindle dysfunction, coupled with a lack of demonstrable motor defect at the same time, suggests that the initial clinical features of acrylamide neuropathy may be partly the consequence of impaired spindle function."}
{"id": "PMID:204770", "title": "Involvement of nicotinic and muscarinic receptors in synaptic transmission in cat superior cervical ganglions reinnervated by vagal primary afferent axons.", "content": "Artificial synapses were established in the superior cervical ganglion reinnervated by vagal afferent fibers by heterologous cross-anastomosis between the cranial end of nodose ganglion and the caudal end of superior cervical ganglion in cats. Formation of functional synapses was evidenced by unilateral mydriasis and contraction of the nictitating membrane in response to inflation of the stomach with a balloon or to electrical stimulation of the afferent vagus. Electron microscopic findings indicated that the vagal afferent fibers terminated in the superior cervical ganglion after cross-anastomosis. In the superior cervical ganglion reinnervated by the afferent vagus, activities of choline acetyltransferase and cholinesterase were higher than those in the preganglionically denervated ganglion, but lower than those in the sympathetic preganglionically reinnervated ganglion. Contractions of the nictitating membrane and postganglionic action potentials evoked by electrical stimulation of the vagal artificial preganglionic trunk in the cross-anastomosed ganglion were blocked by treatment with tetraethylammonium and also with atropine. Atropine did not affect these responses in the normal and the preganglionically reinnervated ganglion, except at an early stage after operation. Comparisons of pharmacological properties in normal, anastomosed, preganglionically denervated and reinnervated ganglia indicated that activation of muscarinic receptors in the anastomosed ganglia is probably not secondary to an incomplete nerve supply, but may be dependent on the nature of the nonmyelinated vagal afferent fibers. The possibility that the transmitter involved may be acetylcholine is discussed.", "contents": "Involvement of nicotinic and muscarinic receptors in synaptic transmission in cat superior cervical ganglions reinnervated by vagal primary afferent axons. Artificial synapses were established in the superior cervical ganglion reinnervated by vagal afferent fibers by heterologous cross-anastomosis between the cranial end of nodose ganglion and the caudal end of superior cervical ganglion in cats. Formation of functional synapses was evidenced by unilateral mydriasis and contraction of the nictitating membrane in response to inflation of the stomach with a balloon or to electrical stimulation of the afferent vagus. Electron microscopic findings indicated that the vagal afferent fibers terminated in the superior cervical ganglion after cross-anastomosis. In the superior cervical ganglion reinnervated by the afferent vagus, activities of choline acetyltransferase and cholinesterase were higher than those in the preganglionically denervated ganglion, but lower than those in the sympathetic preganglionically reinnervated ganglion. Contractions of the nictitating membrane and postganglionic action potentials evoked by electrical stimulation of the vagal artificial preganglionic trunk in the cross-anastomosed ganglion were blocked by treatment with tetraethylammonium and also with atropine. Atropine did not affect these responses in the normal and the preganglionically reinnervated ganglion, except at an early stage after operation. Comparisons of pharmacological properties in normal, anastomosed, preganglionically denervated and reinnervated ganglia indicated that activation of muscarinic receptors in the anastomosed ganglia is probably not secondary to an incomplete nerve supply, but may be dependent on the nature of the nonmyelinated vagal afferent fibers. The possibility that the transmitter involved may be acetylcholine is discussed."}
{"id": "PMID:204771", "title": "Effects of theophylline and N6,O2-dibutyryl adenosine 3':5'-monophosphate on sympathetic ganglionic transmission in rats.", "content": "The effects of theophylline and N6,O2-dibutyryl adenosine 3':5'-monophosphate (DBcAMP) on the amplitude of the postganglionic action potential during and after a 10 Hz repetitive volley, and 50 to 1000 msec after a conditioning stimulus were investigated. The effects of both drugs on some electrophysiological properties of single cells of the isolated superior cervical ganglia of rats were also studied. At low concentrations of theophylline a reversible potentiation of the compound action potential occurred during and after repetitive stimulation at 10 Hz and also after the single conditioning stimulus. This effect was antagonized by atropine. Large concentrations of theophylline exerted a depressive effect only. Low concentrations of DBcAMP caused a reversible initial depression followed by a durable facilitation of transmission during repetitive stimulation. These concentrations potentiated the action potential amplitude after repetitive stimulation, but depressed it after a single conditioning stimulus. Atropine augmented the latter two effects. DBcAMP at large concentrations depressed transmission, but transmission was facilitated after drug washout. Theophylline and guanosine 3':5'-monophosphate, at ineffective concentrations when used singly, potentiated each other and elicited facilitation which was abolished by atropine. Theophylline and DBcAMP at these concentrations depolarized ganglion cells with a time course shorter than that of the aforementioned effects. Both drugs reduced the frequency and amplitude of the spontaneous miniature excitatory postsynaptic potentials. Theophylline did not increase the evoked transmitter release appreciably. On the basis of these findings and the evidence from literature, it is suggested that the reversible facilitatory effect of theophylline may be at least in part due to inhibition of phosphodiesterase of the ganglion cells leading to an enhanced muscarinic transmission. The prolonged facilitatory effect of DBcAMP may result from a durable change in the postsynaptic membrane structure leading to enhanced muscarinic transmission. An enhancement in the muscarinic transmission by both drugs increases the membrane excitability causing recruitment of subthreshold depolarized cells to discharge resulting in facilitation.", "contents": "Effects of theophylline and N6,O2-dibutyryl adenosine 3':5'-monophosphate on sympathetic ganglionic transmission in rats. The effects of theophylline and N6,O2-dibutyryl adenosine 3':5'-monophosphate (DBcAMP) on the amplitude of the postganglionic action potential during and after a 10 Hz repetitive volley, and 50 to 1000 msec after a conditioning stimulus were investigated. The effects of both drugs on some electrophysiological properties of single cells of the isolated superior cervical ganglia of rats were also studied. At low concentrations of theophylline a reversible potentiation of the compound action potential occurred during and after repetitive stimulation at 10 Hz and also after the single conditioning stimulus. This effect was antagonized by atropine. Large concentrations of theophylline exerted a depressive effect only. Low concentrations of DBcAMP caused a reversible initial depression followed by a durable facilitation of transmission during repetitive stimulation. These concentrations potentiated the action potential amplitude after repetitive stimulation, but depressed it after a single conditioning stimulus. Atropine augmented the latter two effects. DBcAMP at large concentrations depressed transmission, but transmission was facilitated after drug washout. Theophylline and guanosine 3':5'-monophosphate, at ineffective concentrations when used singly, potentiated each other and elicited facilitation which was abolished by atropine. Theophylline and DBcAMP at these concentrations depolarized ganglion cells with a time course shorter than that of the aforementioned effects. Both drugs reduced the frequency and amplitude of the spontaneous miniature excitatory postsynaptic potentials. Theophylline did not increase the evoked transmitter release appreciably. On the basis of these findings and the evidence from literature, it is suggested that the reversible facilitatory effect of theophylline may be at least in part due to inhibition of phosphodiesterase of the ganglion cells leading to an enhanced muscarinic transmission. The prolonged facilitatory effect of DBcAMP may result from a durable change in the postsynaptic membrane structure leading to enhanced muscarinic transmission. An enhancement in the muscarinic transmission by both drugs increases the membrane excitability causing recruitment of subthreshold depolarized cells to discharge resulting in facilitation."}
{"id": "PMID:204772", "title": "Control of acetylcholine sensitivity and synapse formation by muscle activity.", "content": "1. The formation of ectopic junctions between the 'foreign' superficial fibular nerve and the soleus muscle of adult rats, and its relation to changes in extrajunctional sensitivity to acetylcholine (ACh), has been studied by denervating the muscle 3-6 weeks after implanting the foreign nerve. 2. The earliest signs of nerve-muscle transmission were seen 2.5-3 days after denervation, in those fibres where the extrajunctional ACh sensitivity first reached its full post-denervation level. The number of innervated fibres continued to increase throughout the first week after denervation until 70-100% of fibres underlying the foreign nerve growth were innervated. 3. Direct stimulation of muscles with chronically implanted electrodes from the time of denervation prevents the formation of functional neuromuscular junctions (n.m.j.s). If stimulation begins 2 or 4 days after denervation, some functional n.m.j.s are formed which can be detected 7-9 days after denervation, though not as many as in the absence of stimulation. 4. Direct stimulation of muscles from the time of denervation prevents the development of detectable extrajunctional ACh sensitivity. If stimulation begins 2 days after denervation nearly maximal sensitivity develops during the third day and then rapidly declines to undetectable levels by the beginning of the eight day after denervation.", "contents": "Control of acetylcholine sensitivity and synapse formation by muscle activity. 1. The formation of ectopic junctions between the 'foreign' superficial fibular nerve and the soleus muscle of adult rats, and its relation to changes in extrajunctional sensitivity to acetylcholine (ACh), has been studied by denervating the muscle 3-6 weeks after implanting the foreign nerve. 2. The earliest signs of nerve-muscle transmission were seen 2.5-3 days after denervation, in those fibres where the extrajunctional ACh sensitivity first reached its full post-denervation level. The number of innervated fibres continued to increase throughout the first week after denervation until 70-100% of fibres underlying the foreign nerve growth were innervated. 3. Direct stimulation of muscles with chronically implanted electrodes from the time of denervation prevents the formation of functional neuromuscular junctions (n.m.j.s). If stimulation begins 2 or 4 days after denervation, some functional n.m.j.s are formed which can be detected 7-9 days after denervation, though not as many as in the absence of stimulation. 4. Direct stimulation of muscles from the time of denervation prevents the development of detectable extrajunctional ACh sensitivity. If stimulation begins 2 days after denervation nearly maximal sensitivity develops during the third day and then rapidly declines to undetectable levels by the beginning of the eight day after denervation."}
{"id": "PMID:204781", "title": "Cyclic AMP and cyclic GMP in rabbit blastocysts.", "content": "Concentrations of both nucleotides were significantly higher in Day-6 than in Day-5 blastocysts but the ratio of cAMP to cGMP changed from 0.5 to 1.5.", "contents": "Cyclic AMP and cyclic GMP in rabbit blastocysts. Concentrations of both nucleotides were significantly higher in Day-6 than in Day-5 blastocysts but the ratio of cAMP to cGMP changed from 0.5 to 1.5."}
{"id": "PMID:204783", "title": "The relationship of puberty to other maturity indicators and body composition in man.", "content": "The purpose of this paper is to examine the relationship between sexual development and other maturational processes in children. The word \"puberty\" is used as a general term to include the development of the secondary sex characters and the attainment of reproductive competence.", "contents": "The relationship of puberty to other maturity indicators and body composition in man. The purpose of this paper is to examine the relationship between sexual development and other maturational processes in children. The word \"puberty\" is used as a general term to include the development of the secondary sex characters and the attainment of reproductive competence."}
{"id": "PMID:204784", "title": "Effect of polymyxin B on the structure and the stability of lipid layers.", "content": "Polymyxin B (PX) does not penetrate phospholipid monolayers and bilayers at low field strength across the lipid layers. The degree of penetration of PX is evaluated from its effect on the capacitance of the monolayers and on the conductance of the bilayers. PX added to one side of a bilayer causes its destabilization, it also enhances destabilization of lipid monolayers at positive electric fields across the surface layer in the direction of the adsorbed PX. PX lowers very little the fluorescence polarization of 1,6-diphenyl 1,3,5 hexatriene embedded in phospholipid vesicles. It is suggested that the penetration mechanism of PX into gram-negative bacteria is based on transient local breakdown of the plasma membrane.", "contents": "Effect of polymyxin B on the structure and the stability of lipid layers. Polymyxin B (PX) does not penetrate phospholipid monolayers and bilayers at low field strength across the lipid layers. The degree of penetration of PX is evaluated from its effect on the capacitance of the monolayers and on the conductance of the bilayers. PX added to one side of a bilayer causes its destabilization, it also enhances destabilization of lipid monolayers at positive electric fields across the surface layer in the direction of the adsorbed PX. PX lowers very little the fluorescence polarization of 1,6-diphenyl 1,3,5 hexatriene embedded in phospholipid vesicles. It is suggested that the penetration mechanism of PX into gram-negative bacteria is based on transient local breakdown of the plasma membrane."}
{"id": "PMID:204785", "title": "Mode of action of theophylline on sodium efflux in barnacle muscle fibers.", "content": "The response of the Na efflux in unpoisoned barnacle fibers to 10 mM theophylline is biphasic; i.e., inhibition is followed by stimulation. The stimulatory response is unaffected by ouabain. Fibers pretreated with ouabain show no transitory inhibition when 10 mM theophylline is applied, but show prompt stimulation the magnitude of which is comparable to that observed with unpoisoned fibers. The same holds true for lower concentrations of theophylline. Prior injection of 500 mM EGTA completely abolishes the biphasic action of 10 mM theophylline. External application of 10 mM theophylline following removal of external Ca2+ fails to bring about a biphasic effect. Ca2+ restoration, however, results in a moderate rise in the Na efflux. External application of 10 mM theophylline stimulates the Na efflux into Ca2+-free artificial seawater (ASW) when the test fibers are pretreated with ouabain. Injection of the protein inhibitor of Walsh leads to reduced stimulation by 10 mM theophylline of the Na efflux in unpoisoned fibers. Injection of the protein inhibitor of Corbin into unpoisoned fibers leads to reduced stimulation by 10 mM theophylline. Injection of cAMP into ouabain-poisoned fibers, following internal application of Corbin's inhibitor and external application of 10 mM theophylline, fails to cause a marked rise in the ouabain-insensitive Na efflux. Injection of Corbin's inhibitor into ouabain-poisoned fibers, following the onset of peak stimulation by 10 mM theophylline, fails to reduce the Na efflux. Fibers injected with 1 mM and 100 mM EGTA and exposed to 10 mM theophylline show a marked reduction in the response of the ouabain-insensitive Na efflux to injected cAMP when the concentration of theophylline is 10 mM. A poor response to injected cAMP is also seen in fibers bathed in Ca-free ASW containing 10 mM theophylline. Theophylline (10 mM) fails to cause an enhanced stimulation of the ouabain-insensitive Na efflux into Ca-free 3 mM-HEPES ASW or 10 mM-Ca2+ -3mM-HEPES ASW following the addition of protons to the bathing medium. An enhanced response is similarly not observed with injected cAMP following the addition of theophylline to the bathing medium. Injection of 8-fluorotheophylline, 3-isobutyl-1-methylxanthine and doxantrazole leads to a marked reduction in the response of the ouabain-insensitive Na efflux to injected cAMP. Contraction always takes place upon injecting these substances. These results are in keeping with the theory that theophylline acts chiefly by reducing myoplasmic pCa(pCa=-log10[Ca2+]), and that a reduced pCa leads to stimulation of the ouabain-insensitive Na efflux as the result of activation of the cGMP-dependent protein kinase system by newly formed cGMP.", "contents": "Mode of action of theophylline on sodium efflux in barnacle muscle fibers. The response of the Na efflux in unpoisoned barnacle fibers to 10 mM theophylline is biphasic; i.e., inhibition is followed by stimulation. The stimulatory response is unaffected by ouabain. Fibers pretreated with ouabain show no transitory inhibition when 10 mM theophylline is applied, but show prompt stimulation the magnitude of which is comparable to that observed with unpoisoned fibers. The same holds true for lower concentrations of theophylline. Prior injection of 500 mM EGTA completely abolishes the biphasic action of 10 mM theophylline. External application of 10 mM theophylline following removal of external Ca2+ fails to bring about a biphasic effect. Ca2+ restoration, however, results in a moderate rise in the Na efflux. External application of 10 mM theophylline stimulates the Na efflux into Ca2+-free artificial seawater (ASW) when the test fibers are pretreated with ouabain. Injection of the protein inhibitor of Walsh leads to reduced stimulation by 10 mM theophylline of the Na efflux in unpoisoned fibers. Injection of the protein inhibitor of Corbin into unpoisoned fibers leads to reduced stimulation by 10 mM theophylline. Injection of cAMP into ouabain-poisoned fibers, following internal application of Corbin's inhibitor and external application of 10 mM theophylline, fails to cause a marked rise in the ouabain-insensitive Na efflux. Injection of Corbin's inhibitor into ouabain-poisoned fibers, following the onset of peak stimulation by 10 mM theophylline, fails to reduce the Na efflux. Fibers injected with 1 mM and 100 mM EGTA and exposed to 10 mM theophylline show a marked reduction in the response of the ouabain-insensitive Na efflux to injected cAMP when the concentration of theophylline is 10 mM. A poor response to injected cAMP is also seen in fibers bathed in Ca-free ASW containing 10 mM theophylline. Theophylline (10 mM) fails to cause an enhanced stimulation of the ouabain-insensitive Na efflux into Ca-free 3 mM-HEPES ASW or 10 mM-Ca2+ -3mM-HEPES ASW following the addition of protons to the bathing medium. An enhanced response is similarly not observed with injected cAMP following the addition of theophylline to the bathing medium. Injection of 8-fluorotheophylline, 3-isobutyl-1-methylxanthine and doxantrazole leads to a marked reduction in the response of the ouabain-insensitive Na efflux to injected cAMP. Contraction always takes place upon injecting these substances. These results are in keeping with the theory that theophylline acts chiefly by reducing myoplasmic pCa(pCa=-log10[Ca2+]), and that a reduced pCa leads to stimulation of the ouabain-insensitive Na efflux as the result of activation of the cGMP-dependent protein kinase system by newly formed cGMP."}
{"id": "PMID:204786", "title": "Effect of basic protein from human central nervous system myelin on lipid bilayer structure.", "content": "The effect of myelin basic protein from normal human central nervous system on lipid organization has been investigated by studying model membranes containing the protein by differential scanning calorimetry or electron spin resonance spectroscopy. Basic protein was found to decrease the phase transition temperature of dipalmitoyl phosphatidylglycerol, phosphatidic acid, and phosphatidylserine. The protein had a greater effect on the freezing temperature, measured from the cooling scan, than on the melting temperature, measured from the heating scan. These results are consistent with partial penetration of parts of the protein into the hydrocarbon region of the bilayer in the liquid crystalline state and partial freezing out when the lipid has been cooled below its phase transition temperature. The effect of the protein on fatty acid chain packing was investigated by using a series of fatty acid spin labels with the nitroxide group located at different positions along the chain. If the protein has not yet penetrated, it increases the order throughout the bilayer in the gel phase, probably by decreasing the repulsion between the lipid polar head groups. Above the phase transition temperature, when parts of it are able to pentrate, it decreases the motion of the lipid fatty acid chains greatly near the polar head group region, but has little or no effect near the interior of the bilayer. Upon cooling again the protein still decreases the motion near the polar head group region but increases it greatly in the interior. Thus, the protein penetrates partway into the bilayer, distorts the packing of the lipid fatty acid chains, and prevents recrystallization, thus decreasing the phase transition temperature. The magnitude of the effect varied with the lipid and was greatest for phosphatidic acid and phosphatidylglycerol. It could be reversed upon cooling for phosphatidylglycerol but not phosphatidic acid. The protein was only observed to decrease the phase transition temperature of phosphatidylserine upon cooling. It had only a small effect on phosphatidylethanolamine and no effect on phosphatidylcholine. Thus, the protein may penetrate to a different extent into different lipids even if it binds to the polar head group region by electrostatic interactions.", "contents": "Effect of basic protein from human central nervous system myelin on lipid bilayer structure. The effect of myelin basic protein from normal human central nervous system on lipid organization has been investigated by studying model membranes containing the protein by differential scanning calorimetry or electron spin resonance spectroscopy. Basic protein was found to decrease the phase transition temperature of dipalmitoyl phosphatidylglycerol, phosphatidic acid, and phosphatidylserine. The protein had a greater effect on the freezing temperature, measured from the cooling scan, than on the melting temperature, measured from the heating scan. These results are consistent with partial penetration of parts of the protein into the hydrocarbon region of the bilayer in the liquid crystalline state and partial freezing out when the lipid has been cooled below its phase transition temperature. The effect of the protein on fatty acid chain packing was investigated by using a series of fatty acid spin labels with the nitroxide group located at different positions along the chain. If the protein has not yet penetrated, it increases the order throughout the bilayer in the gel phase, probably by decreasing the repulsion between the lipid polar head groups. Above the phase transition temperature, when parts of it are able to pentrate, it decreases the motion of the lipid fatty acid chains greatly near the polar head group region, but has little or no effect near the interior of the bilayer. Upon cooling again the protein still decreases the motion near the polar head group region but increases it greatly in the interior. Thus, the protein penetrates partway into the bilayer, distorts the packing of the lipid fatty acid chains, and prevents recrystallization, thus decreasing the phase transition temperature. The magnitude of the effect varied with the lipid and was greatest for phosphatidic acid and phosphatidylglycerol. It could be reversed upon cooling for phosphatidylglycerol but not phosphatidic acid. The protein was only observed to decrease the phase transition temperature of phosphatidylserine upon cooling. It had only a small effect on phosphatidylethanolamine and no effect on phosphatidylcholine. Thus, the protein may penetrate to a different extent into different lipids even if it binds to the polar head group region by electrostatic interactions."}
{"id": "PMID:204796", "title": "Cytotoxic activity of methylene bis-nucleotides.", "content": "New facts relating to the mechanism of cytotoxic and antitumor activity of formaldehyde-treated RNA and its hydrolysates have been revealed. Synthetic methylene bis-nucleotides and, in particular, methylene bis-nucleosides have a cytotoxic effect on cultured human adenocarcinoma cells (line HCCL). The cytotoxic effect of methylene bis-derivatives of the guanine series was most pronounced. In addition, methylene bis-nucleotides were depbosphorylated in the cell culture medium. Chromosome aberrations were induced by alkaline hydrolysate of dialyzed formaldehyde-treated RNA in which 39% of purine nucleotdies were modified to methylene bis-derivatives.", "contents": "Cytotoxic activity of methylene bis-nucleotides. New facts relating to the mechanism of cytotoxic and antitumor activity of formaldehyde-treated RNA and its hydrolysates have been revealed. Synthetic methylene bis-nucleotides and, in particular, methylene bis-nucleosides have a cytotoxic effect on cultured human adenocarcinoma cells (line HCCL). The cytotoxic effect of methylene bis-derivatives of the guanine series was most pronounced. In addition, methylene bis-nucleotides were depbosphorylated in the cell culture medium. Chromosome aberrations were induced by alkaline hydrolysate of dialyzed formaldehyde-treated RNA in which 39% of purine nucleotdies were modified to methylene bis-derivatives."}
{"id": "PMID:204797", "title": "Effect of the Fv-1 locus in vivo: host range pseudotypes of murine sarcoma virus.", "content": "Fv-1-specific host-range pseudotypes of murine sarcoma virus (MuSV) were developed by rescue from nonproducer cells with N- or B-tropic leukemia viruses. The MuSV(B) and MuSV(N) pseudotype viruses were tested in vitro and were restricted specifically by the Fv-1 gene locus. When the pseudo-type viruses were tested in vivo in mice of specific Fv-1 geno-types, tumor induction was completely restricted in nonpermissive animals, including athymic nude mice, whereas tumors grew progressively in permissive animals. All tumors regressed in adult heterozygous mice, but not in adult athymic nude mice.", "contents": "Effect of the Fv-1 locus in vivo: host range pseudotypes of murine sarcoma virus. Fv-1-specific host-range pseudotypes of murine sarcoma virus (MuSV) were developed by rescue from nonproducer cells with N- or B-tropic leukemia viruses. The MuSV(B) and MuSV(N) pseudotype viruses were tested in vitro and were restricted specifically by the Fv-1 gene locus. When the pseudo-type viruses were tested in vivo in mice of specific Fv-1 geno-types, tumor induction was completely restricted in nonpermissive animals, including athymic nude mice, whereas tumors grew progressively in permissive animals. All tumors regressed in adult heterozygous mice, but not in adult athymic nude mice."}
{"id": "PMID:204798", "title": "Simian virus 40 (SV40) production from SV40-transformed human amnion cells of established lines.", "content": "Sixteen established cell lines of simian virus 40 (SV40)-transformed human amnion cells were examined for SV40 production. Many of these lines produced SV40 for extensive periods. Virus production had not ceased for 2 lines after 18 months, for 3 lines after 12 months, and for 3 lines at 3 months after recovery from \"crisis\". Three lines became virus-free in the first month, 1 line in the second month, 1 in the third month, and 1 in the fourth month, and 2 lines stopped virus production between 6 and 11 months after recovery. The virus titers were relatively low. Inclusion body-containing cells were infrequent. In contrast, in most cultures of SV40-transformed human fibroblasts rescued from crisis, no infectious virus was demonstrated, although exceptions have been reported. Virus was produced after heterokaryon formation of cells of the virus-free amnion lines with CV-1 cells in the presence of inactivated Sendai virus, as observed for SV40-transformed human fibroblasts. During the crisis period, some of the SV40-transformed amnion cells produced substantial amounts of virus. Titers decreased during the later periods of crisis. The most pronounced decrease in titers was in cultures from which established lines were recovered.", "contents": "Simian virus 40 (SV40) production from SV40-transformed human amnion cells of established lines. Sixteen established cell lines of simian virus 40 (SV40)-transformed human amnion cells were examined for SV40 production. Many of these lines produced SV40 for extensive periods. Virus production had not ceased for 2 lines after 18 months, for 3 lines after 12 months, and for 3 lines at 3 months after recovery from \"crisis\". Three lines became virus-free in the first month, 1 line in the second month, 1 in the third month, and 1 in the fourth month, and 2 lines stopped virus production between 6 and 11 months after recovery. The virus titers were relatively low. Inclusion body-containing cells were infrequent. In contrast, in most cultures of SV40-transformed human fibroblasts rescued from crisis, no infectious virus was demonstrated, although exceptions have been reported. Virus was produced after heterokaryon formation of cells of the virus-free amnion lines with CV-1 cells in the presence of inactivated Sendai virus, as observed for SV40-transformed human fibroblasts. During the crisis period, some of the SV40-transformed amnion cells produced substantial amounts of virus. Titers decreased during the later periods of crisis. The most pronounced decrease in titers was in cultures from which established lines were recovered."}
{"id": "PMID:204799", "title": "Induction of intracisternal type A particles by 5-bromo-2'-deoxyuridine in rat hepatoma cells.", "content": "Electron microscopic examination of hepatoma tissue culture (HTC) cells revealed low numbers of intracisternal type A particles (IAP) and type C viruses. Exposure of HTC cells to either 10(-4) or 10(-5) M5-bromo-2'-deoxyuridine (BUdR) caused a more than 50-fold increase in the number of IAP observed with the electron microscope. The number of IAP increased after only 2 days of growth in 10(-5) M BUdR, whereas 3 days of growth in 10(-4) m BUdR were necessary to observe an increase. A 2-day pulse of 10(-4) M BUdR was also sufficient to cause the increase in type A particles, provided the cells were continued in culture for another 2 days. Unlike many other cell lines, HTC cells treated with BUdR did not show an increase in type C viruses. This conclusion was based on the observations that BUdR treatment caused no detectable increase in extracellular particulate viral reverse transcriptase or in viral RNA complementary to a DNA probe made to a rat endogenous type C virus (RaLV).", "contents": "Induction of intracisternal type A particles by 5-bromo-2'-deoxyuridine in rat hepatoma cells. Electron microscopic examination of hepatoma tissue culture (HTC) cells revealed low numbers of intracisternal type A particles (IAP) and type C viruses. Exposure of HTC cells to either 10(-4) or 10(-5) M5-bromo-2'-deoxyuridine (BUdR) caused a more than 50-fold increase in the number of IAP observed with the electron microscope. The number of IAP increased after only 2 days of growth in 10(-5) M BUdR, whereas 3 days of growth in 10(-4) m BUdR were necessary to observe an increase. A 2-day pulse of 10(-4) M BUdR was also sufficient to cause the increase in type A particles, provided the cells were continued in culture for another 2 days. Unlike many other cell lines, HTC cells treated with BUdR did not show an increase in type C viruses. This conclusion was based on the observations that BUdR treatment caused no detectable increase in extracellular particulate viral reverse transcriptase or in viral RNA complementary to a DNA probe made to a rat endogenous type C virus (RaLV)."}
{"id": "PMID:204800", "title": "Variation of properties of chrysotile asbestos subjected to milling.", "content": "Mechanical milling is commonly used to produce short chrysotile asbestos for experimental purposes. Such manipulation also decreases fiber crystallinity, alters Si-O and Mg-O interlayer bonding, induces coordination changes in the brucite layer, diminishes the ability of fiber to reduce specific free radicals and physisorb organic molecules, and decreases hemolytic potency and antagonist sorption capabilities. The degree of alteration is related to the time of milling. Results of biological experimentation with these materials must be interpreted with caution. Interaction mechanisms in the biological setting are suggested for chrysotile fiber.", "contents": "Variation of properties of chrysotile asbestos subjected to milling. Mechanical milling is commonly used to produce short chrysotile asbestos for experimental purposes. Such manipulation also decreases fiber crystallinity, alters Si-O and Mg-O interlayer bonding, induces coordination changes in the brucite layer, diminishes the ability of fiber to reduce specific free radicals and physisorb organic molecules, and decreases hemolytic potency and antagonist sorption capabilities. The degree of alteration is related to the time of milling. Results of biological experimentation with these materials must be interpreted with caution. Interaction mechanisms in the biological setting are suggested for chrysotile fiber."}
{"id": "PMID:204801", "title": "Latex agglutination test for amoebiasis in Pakistani patients with chronic 'obscure' liver enlargements.", "content": "The latex agglutination test for amoebiasis was done in 50 Pakistani patients in whom a clinical diagnosis of chronic non-supparative amoebic hepatitis was made on the basis of liver enlargement associated with chronic recurrent abdominal disturbance. The serological test was negative in 32 (64%) and positive in 18 (36%). Examination of stool specimens showed a higher frequency of E. histolytica in serology positive patients. The liver biopsy findings were variable and included normal histology in 40 percent and non-specific changes in another 34 per cent of the patients. There was evidence of early abscess formation in one patient with a strongly positive serological reaction. Chronic liver enlargements in this region form a heterogenous group and the existence of chronic non-suppurative amoebic hepatitis as a clinico-pathological entity remains doubtful.", "contents": "Latex agglutination test for amoebiasis in Pakistani patients with chronic 'obscure' liver enlargements. The latex agglutination test for amoebiasis was done in 50 Pakistani patients in whom a clinical diagnosis of chronic non-supparative amoebic hepatitis was made on the basis of liver enlargement associated with chronic recurrent abdominal disturbance. The serological test was negative in 32 (64%) and positive in 18 (36%). Examination of stool specimens showed a higher frequency of E. histolytica in serology positive patients. The liver biopsy findings were variable and included normal histology in 40 percent and non-specific changes in another 34 per cent of the patients. There was evidence of early abscess formation in one patient with a strongly positive serological reaction. Chronic liver enlargements in this region form a heterogenous group and the existence of chronic non-suppurative amoebic hepatitis as a clinico-pathological entity remains doubtful."}
{"id": "PMID:204802", "title": "Toxoplasmosis, distemper, and herpesvirus infection in a skunk (Mephitis mephitis).", "content": "A striped skunk (Mephitis mephitis) showing abnormal behavior had histopathologic lesions of toxoplasmosis and canine distemper in addition to intranuclear, eosinophilic inclusions in the reticuloendothelial cells of the spleen, liver and lung. The inclusions, on electron microscopic examination, were compatible with herpesvirus infection.", "contents": "Toxoplasmosis, distemper, and herpesvirus infection in a skunk (Mephitis mephitis). A striped skunk (Mephitis mephitis) showing abnormal behavior had histopathologic lesions of toxoplasmosis and canine distemper in addition to intranuclear, eosinophilic inclusions in the reticuloendothelial cells of the spleen, liver and lung. The inclusions, on electron microscopic examination, were compatible with herpesvirus infection."}
{"id": "PMID:204803", "title": "Oral contraceptives and nonfatal myocardial infarction.", "content": "We obtained information on 107 women younger than 46 years who were discharged from a hospital with a diagnosis of acute myocardial infarction. In the series 26 women were otherwise apparently healthy and potentially childbearing. Among these 26 women, 20 (77%) were taking oral contraceptives just prior to admission, and one was taking conjugated estrogens. Among 59 control women, 14 (24%) were taking oral contraceptives and one was taking conjugated estrogens. The relative risk estimate, comparing oral contraceptive users with nonusers, is 14 with 90% confidence limits of 5.5 and 37. All but two of the 26 women were cigarette smokers. While this illness is rare in most healthy young women, the risk in women older than about 37 years who both smoke and take oral contraceptive appears to be high.", "contents": "Oral contraceptives and nonfatal myocardial infarction. We obtained information on 107 women younger than 46 years who were discharged from a hospital with a diagnosis of acute myocardial infarction. In the series 26 women were otherwise apparently healthy and potentially childbearing. Among these 26 women, 20 (77%) were taking oral contraceptives just prior to admission, and one was taking conjugated estrogens. Among 59 control women, 14 (24%) were taking oral contraceptives and one was taking conjugated estrogens. The relative risk estimate, comparing oral contraceptive users with nonusers, is 14 with 90% confidence limits of 5.5 and 37. All but two of the 26 women were cigarette smokers. While this illness is rare in most healthy young women, the risk in women older than about 37 years who both smoke and take oral contraceptive appears to be high."}
{"id": "PMID:204804", "title": "Noncontraceptive estrogens and nonfatal myocardial infarction.", "content": "We obtained information on 107 women younger than 46 years discharged from a hospital with a diagnosis of acute myocardial infarction. In the series there were 17 women aged 39 to 45 years who were otherwise apparently healthy and had had a natural menopause, hysterectomy, or tubal ligation or whose spouse had had a vasectomy. Among them, nine (53%) were taking noncontraceptive estrogens just prior to admission. Among 34 control women, four (12%) were taking estrogens. The relative risk estimate, comparing estrogen users with nonusers, is 7.5, with 90% confidence limits of 2.4 and 24. All but one of the 17 ml subjects were cigarette smokers. While this illness is rare in most healthy young women, the risk in women older than about 38 years who both smoke and take estrogens appears to be substantial.", "contents": "Noncontraceptive estrogens and nonfatal myocardial infarction. We obtained information on 107 women younger than 46 years discharged from a hospital with a diagnosis of acute myocardial infarction. In the series there were 17 women aged 39 to 45 years who were otherwise apparently healthy and had had a natural menopause, hysterectomy, or tubal ligation or whose spouse had had a vasectomy. Among them, nine (53%) were taking noncontraceptive estrogens just prior to admission. Among 34 control women, four (12%) were taking estrogens. The relative risk estimate, comparing estrogen users with nonusers, is 7.5, with 90% confidence limits of 2.4 and 24. All but one of the 17 ml subjects were cigarette smokers. While this illness is rare in most healthy young women, the risk in women older than about 38 years who both smoke and take estrogens appears to be substantial."}
{"id": "PMID:204806", "title": "Renal tranplantation in type 1 glycogenosis. Failure to improve glucose metabolism.", "content": "In glycogenosis type 1 (GT1), glucose synthesis is deficient due to absence of glucose-6-phosphatase. Development of renal failure in such a patient provided the opportunity to test whether or not this metabolic defect could be reversed by a renal allograft, which contains the missing enzyme and has potential for glucose synthesis. Despite normalization of renal function and both glucocorticoid therapy and the infusion of amino-acid precursors of glucose, fasting hypoglycemia persisted unabated. We conclude that a funtioning renal allograft is incapable of meeting the metabolic demands of a patient with glucose-6-phosphatase deficiency.", "contents": "Renal tranplantation in type 1 glycogenosis. Failure to improve glucose metabolism. In glycogenosis type 1 (GT1), glucose synthesis is deficient due to absence of glucose-6-phosphatase. Development of renal failure in such a patient provided the opportunity to test whether or not this metabolic defect could be reversed by a renal allograft, which contains the missing enzyme and has potential for glucose synthesis. Despite normalization of renal function and both glucocorticoid therapy and the infusion of amino-acid precursors of glucose, fasting hypoglycemia persisted unabated. We conclude that a funtioning renal allograft is incapable of meeting the metabolic demands of a patient with glucose-6-phosphatase deficiency."}
{"id": "PMID:204820", "title": "Possible involvement of cyclic AMP in inflammation induced by a surfactant.", "content": "Alkyldimethylbenzylammonium chloride (alkyl-DBAC), a cationic surfactant, produces acute exudative inflammation accompanied by an enhancement of energy metabolism. The mechanism of metabolic changes, consequently the cyclic AMP level and the effects of certain drugs were determined in the gastrocnemius muscles of rats in which acute exudative inflammation had been induced by intramuscular injections of alkyl-DBAC. A transient increase in the cyclic AMP level was noted at 15 to 30 minutes after the injection of alkyl-DBAC, and this elevation was antagonized by chlorpromazine, diphenhydramine, promethazine, aspirin and indomethacin. The time course of increasing tendency in the cyclic AMP level after the injection of histamine closely paralleled that of alkyl-DBAC. These results suggest that cyclic AMP may be involved in the metabolic changes with inflammation induced by alkyl-DBAC.", "contents": "Possible involvement of cyclic AMP in inflammation induced by a surfactant. Alkyldimethylbenzylammonium chloride (alkyl-DBAC), a cationic surfactant, produces acute exudative inflammation accompanied by an enhancement of energy metabolism. The mechanism of metabolic changes, consequently the cyclic AMP level and the effects of certain drugs were determined in the gastrocnemius muscles of rats in which acute exudative inflammation had been induced by intramuscular injections of alkyl-DBAC. A transient increase in the cyclic AMP level was noted at 15 to 30 minutes after the injection of alkyl-DBAC, and this elevation was antagonized by chlorpromazine, diphenhydramine, promethazine, aspirin and indomethacin. The time course of increasing tendency in the cyclic AMP level after the injection of histamine closely paralleled that of alkyl-DBAC. These results suggest that cyclic AMP may be involved in the metabolic changes with inflammation induced by alkyl-DBAC."}
{"id": "PMID:204821", "title": "Studies on beta-pyridylcarbinol as a precursor of nicotinamide adenine dinucleotide.", "content": "The major part of orally administered beta-pyridylcarbinol was converted to nicotinic acid in the gastrointestinal tract, whereas that administered intraperitoneally was partially converted to nicotinic acid in the liver. The conversion of this compound to nicotinic acid in both the gastrointestinal tract and liver involved enzymatic processes. The converted nicotinic acid from beta-pyridylcarbinol may play a dominant role in the biological actions of beta-pyridylcarbinol and possibly involves in the synthesis of NAD via Preiss-Handler's pathway.", "contents": "Studies on beta-pyridylcarbinol as a precursor of nicotinamide adenine dinucleotide. The major part of orally administered beta-pyridylcarbinol was converted to nicotinic acid in the gastrointestinal tract, whereas that administered intraperitoneally was partially converted to nicotinic acid in the liver. The conversion of this compound to nicotinic acid in both the gastrointestinal tract and liver involved enzymatic processes. The converted nicotinic acid from beta-pyridylcarbinol may play a dominant role in the biological actions of beta-pyridylcarbinol and possibly involves in the synthesis of NAD via Preiss-Handler's pathway."}
{"id": "PMID:204825", "title": "[Effect of neural regulation on the fluctuations in the intervals between cardiac contractions and the force of the contractions].", "content": "Statistical analysis of the cardiac rhythm according to the R--R intervals and the force of contractions according to their amplitude was undertaken. The variation coefficient (N%) reflecting the degree of irregularity of intervals between the contractions and the force of contractions during maximum cardiac hyperfunction induced by clamping the aorta for 30 sec was determined. Vagotomy led to a decrease in the irregularity for cardiac rhythm and force of cardiac contractions.", "contents": "[Effect of neural regulation on the fluctuations in the intervals between cardiac contractions and the force of the contractions]. Statistical analysis of the cardiac rhythm according to the R--R intervals and the force of contractions according to their amplitude was undertaken. The variation coefficient (N%) reflecting the degree of irregularity of intervals between the contractions and the force of contractions during maximum cardiac hyperfunction induced by clamping the aorta for 30 sec was determined. Vagotomy led to a decrease in the irregularity for cardiac rhythm and force of cardiac contractions."}
{"id": "PMID:204826", "title": "[Histology, fine structure and differentiation of experimental Wilms tumors (author's transl)].", "content": "Histologic studies indicate that the cycasin-induced Wilms' tumor in the rat is equal to human nephroblastoma in appearance. Therefore, it may represent an interesting system for experimental oncology. In electron microscopy, the spindle cells of the sarcoma region mostly represent tubular cells. Besides, the author's results showed that preexisting mesenchyma cells and blood vessels also form part of the tumor. Electron microscopy studies have shown that cycasin feeding will lead to early cellular changes indicating that cycasin exercises a nucleotoxic effect. Present results do not favor the dysontogenic concept of the formation of Wilms' tumor, since this tumor can be induced diaplacentally.", "contents": "[Histology, fine structure and differentiation of experimental Wilms tumors (author's transl)]. Histologic studies indicate that the cycasin-induced Wilms' tumor in the rat is equal to human nephroblastoma in appearance. Therefore, it may represent an interesting system for experimental oncology. In electron microscopy, the spindle cells of the sarcoma region mostly represent tubular cells. Besides, the author's results showed that preexisting mesenchyma cells and blood vessels also form part of the tumor. Electron microscopy studies have shown that cycasin feeding will lead to early cellular changes indicating that cycasin exercises a nucleotoxic effect. Present results do not favor the dysontogenic concept of the formation of Wilms' tumor, since this tumor can be induced diaplacentally."}
{"id": "PMID:204827", "title": "[Inguinal Wilms' tumor (author's transl)].", "content": "Case report on a small inguinal Wilms' tumor in a 3-year-old boy. Their is strong evidence, that this heterotopic Wilms' tumor developed in dysplastic renal tissue.", "contents": "[Inguinal Wilms' tumor (author's transl)]. Case report on a small inguinal Wilms' tumor in a 3-year-old boy. Their is strong evidence, that this heterotopic Wilms' tumor developed in dysplastic renal tissue."}
{"id": "PMID:204828", "title": "Control of plasma aldosterone in diabetic patients with hyporeninemic hypoaldosteronism.", "content": "In three patients with diabetes and hyporeninemic hypoaldosteronism changes in renin activity, plasma aldosterone and cortisol were examined under various conditions: orthostasis and intravenous furosemide, infusion of synthetic beta1-24 ACTH on two consecutive days and diurnal variations in basal hormone fluctuations. Each patient showed unmeasurably low renin activity unresponsive to orthostasis and intravenous furosemide while plasma aldosterone was below normal range. Under ACTH-infusion only marked increases in aldosterone were observed in one patient whereas cortisol responded normally in all diabetics tested. Analysis of diurnal night day fluctuations (20.00-8.00) in plasma aldosterone and cortisol revealed a close and statistically significant relationship between both hormones in each of the three patients (p less then 0.05-less than 0.001). Variations in plasma aldosterone thus were mediated through changes in endogenous pituitary ACTH. Compared with normal controls however, diurnal aldosterone curves were set at a lower level. Our results demonstrate that a reduced sensitivity of the adrenal gland to ACTH is not responsible for the observed subnormal plasma aldosterone levels in these patients. Therefore, the lack of circulating angiotensin II seems to be the causative reason of hypoaldosteronism. The exact mechanism of undetectable renin activity in these patients remains unknown.", "contents": "Control of plasma aldosterone in diabetic patients with hyporeninemic hypoaldosteronism. In three patients with diabetes and hyporeninemic hypoaldosteronism changes in renin activity, plasma aldosterone and cortisol were examined under various conditions: orthostasis and intravenous furosemide, infusion of synthetic beta1-24 ACTH on two consecutive days and diurnal variations in basal hormone fluctuations. Each patient showed unmeasurably low renin activity unresponsive to orthostasis and intravenous furosemide while plasma aldosterone was below normal range. Under ACTH-infusion only marked increases in aldosterone were observed in one patient whereas cortisol responded normally in all diabetics tested. Analysis of diurnal night day fluctuations (20.00-8.00) in plasma aldosterone and cortisol revealed a close and statistically significant relationship between both hormones in each of the three patients (p less then 0.05-less than 0.001). Variations in plasma aldosterone thus were mediated through changes in endogenous pituitary ACTH. Compared with normal controls however, diurnal aldosterone curves were set at a lower level. Our results demonstrate that a reduced sensitivity of the adrenal gland to ACTH is not responsible for the observed subnormal plasma aldosterone levels in these patients. Therefore, the lack of circulating angiotensin II seems to be the causative reason of hypoaldosteronism. The exact mechanism of undetectable renin activity in these patients remains unknown."}
{"id": "PMID:204830", "title": "In vitro demonstration of Mallory body formation in liver cells from rats fed diethylnitrosamine.", "content": "Epithelioid liver cells were established in culture from rats sacrificed 10 to 18 weeks after the administration of the hepatocarcinogen diethylnitrosamine in their drinking water. After approximately 3 months in vitro, more than half the cells propagated from rats that developed hepatocellular carcinomas had bean-shaped, acentrically displaced nuclei with large juxtanuclear homogeneous appearing areas resembling the hyalin or Mallory bodies in the livers of chronic alcoholics. These abnormalities were not seen in the livers of origin, but were retained in the carcinomas that formed after the cultured cells containing such juxtanuclear hyalin inclusions were inoculated into young rats or nude (i.e., thymusless) mice; these features persisted upon reestablishment and continuous passage of the tumor cells in culture. The cells were further characterized by their karyotypes and their growth properties in liquid media and soft agar. By transmission electron microscopy the hyaline bodies in the culture tumor cells were shown to consist of a disorganized meshwork of filaments. Examination by incubating cells with cytochalasin B and by using antiactin and anti-DNase antisera as indirect immunofluorescence probes also revealed a disturbance in the cytoskeleton.", "contents": "In vitro demonstration of Mallory body formation in liver cells from rats fed diethylnitrosamine. Epithelioid liver cells were established in culture from rats sacrificed 10 to 18 weeks after the administration of the hepatocarcinogen diethylnitrosamine in their drinking water. After approximately 3 months in vitro, more than half the cells propagated from rats that developed hepatocellular carcinomas had bean-shaped, acentrically displaced nuclei with large juxtanuclear homogeneous appearing areas resembling the hyalin or Mallory bodies in the livers of chronic alcoholics. These abnormalities were not seen in the livers of origin, but were retained in the carcinomas that formed after the cultured cells containing such juxtanuclear hyalin inclusions were inoculated into young rats or nude (i.e., thymusless) mice; these features persisted upon reestablishment and continuous passage of the tumor cells in culture. The cells were further characterized by their karyotypes and their growth properties in liquid media and soft agar. By transmission electron microscopy the hyaline bodies in the culture tumor cells were shown to consist of a disorganized meshwork of filaments. Examination by incubating cells with cytochalasin B and by using antiactin and anti-DNase antisera as indirect immunofluorescence probes also revealed a disturbance in the cytoskeleton."}
{"id": "PMID:204831", "title": "Effects of chronic and acute ethanol administration on sleep in laboratory rats.", "content": "Long- and short-term administration of nonintoxicating doses of ethanol affected sleep parameters in rats.", "contents": "Effects of chronic and acute ethanol administration on sleep in laboratory rats. Long- and short-term administration of nonintoxicating doses of ethanol affected sleep parameters in rats."}
{"id": "PMID:204832", "title": "Evaluation of a national training program for consultants in alcoholism treatment.", "content": "A method for evaluating the training of persons hired to develop alcoholism treatment programs in government and private industry is described.", "contents": "Evaluation of a national training program for consultants in alcoholism treatment. A method for evaluating the training of persons hired to develop alcoholism treatment programs in government and private industry is described."}
{"id": "PMID:204838", "title": "Cyclic nucleotide levels in resting and mitogen-stimulated spleen cell suspensions from young and old mice.", "content": "The levels of cyclic adenosine 3', 5'-monophosphate (cAMP) in suspensions of unstimulated spleen cells from tumor-free 30-month old (C57BL/10Sn X C3H/HeDiSn)F1 hybrid mice averaged only 14% of that of 6-month old mice. By contrast, the level of cyclic guanosine 3', 5'-monophosphate (cGMP) in spleen cell suspensions from old mice was about 270% that of young mice. The cAMP/cGMP ratio for the unstimulated (resting) state showed a decline by 30 months to about 5% of its 6-month value. Cyclic nucleotide levels were also measured in cell suspensions from old and young mice at intervals over a two hour period following in vitro stimulation with the plant mitogens phytohemagglutinin, concanavalin-A and pokeweed mitogen. Quantitative and in some instances qualitative differences in responses were noted. These results might conceivably reflect either age-related changes in the splenic lymphoid cell subpopulations or intrinsic cellular alterations or both. It is unlikely that changes of this degree could be wholly explained by population shifts. An imbalance in cyclic nucleotide levels in both resting and stimulated lymphoid cells in older animals might contribute to the immune dysfunction known to occur with normal aging.", "contents": "Cyclic nucleotide levels in resting and mitogen-stimulated spleen cell suspensions from young and old mice. The levels of cyclic adenosine 3', 5'-monophosphate (cAMP) in suspensions of unstimulated spleen cells from tumor-free 30-month old (C57BL/10Sn X C3H/HeDiSn)F1 hybrid mice averaged only 14% of that of 6-month old mice. By contrast, the level of cyclic guanosine 3', 5'-monophosphate (cGMP) in spleen cell suspensions from old mice was about 270% that of young mice. The cAMP/cGMP ratio for the unstimulated (resting) state showed a decline by 30 months to about 5% of its 6-month value. Cyclic nucleotide levels were also measured in cell suspensions from old and young mice at intervals over a two hour period following in vitro stimulation with the plant mitogens phytohemagglutinin, concanavalin-A and pokeweed mitogen. Quantitative and in some instances qualitative differences in responses were noted. These results might conceivably reflect either age-related changes in the splenic lymphoid cell subpopulations or intrinsic cellular alterations or both. It is unlikely that changes of this degree could be wholly explained by population shifts. An imbalance in cyclic nucleotide levels in both resting and stimulated lymphoid cells in older animals might contribute to the immune dysfunction known to occur with normal aging."}
{"id": "PMID:204839", "title": "[Hepatic fibrosis--mechanism, dynamics and clinical consequences (author's transl)].", "content": "Hepatic fibrosis may result from collapse after hepatocellular necrosis or from new formation of connective tissue. Fibroplasia, particularly within the lobular parenchyma, is a dynamic process. Newer cellular and biochemical investigations clarified its various steps. The process begins with stimulation of cells to connective tissue formation and can be divided into (1) intracellular synthesis, (2) extracellular maturation, and (3) collagen breakdown. The turnover of the connective tissue in the liver is conspicuously increased in chronic hepatitis of any type, as indicated by an elevation of several cellular and metabolic parameters. They are particularly raised in chronic hepatitis and in alcoholic liver injury. Further development of these parameters in the future should facilitate the analysis of the dynamics of fibroplasia. The strongest stimuli for hepatic fibroplasia are hepatocellular necrosis and inflammation, but ethyl alcohol and steatosis are also stimulating, though to a lesser degree. This explains the particular elevation of the fibroplastic parameters in alcoholic hepatitis. It points, however, also to the possibility that cirrhosis might develop without significant hepatocellular necrosis and inflammation. Perihepatocellular, periductular, and septal fibrosis are the functionally most important localizations leading to additional hepatic injury. The initiation of these types of fibrosis by liver injury points to a vicious circle. Specific anti-fibroplastic therapy is still in infancy.", "contents": "[Hepatic fibrosis--mechanism, dynamics and clinical consequences (author's transl)]. Hepatic fibrosis may result from collapse after hepatocellular necrosis or from new formation of connective tissue. Fibroplasia, particularly within the lobular parenchyma, is a dynamic process. Newer cellular and biochemical investigations clarified its various steps. The process begins with stimulation of cells to connective tissue formation and can be divided into (1) intracellular synthesis, (2) extracellular maturation, and (3) collagen breakdown. The turnover of the connective tissue in the liver is conspicuously increased in chronic hepatitis of any type, as indicated by an elevation of several cellular and metabolic parameters. They are particularly raised in chronic hepatitis and in alcoholic liver injury. Further development of these parameters in the future should facilitate the analysis of the dynamics of fibroplasia. The strongest stimuli for hepatic fibroplasia are hepatocellular necrosis and inflammation, but ethyl alcohol and steatosis are also stimulating, though to a lesser degree. This explains the particular elevation of the fibroplastic parameters in alcoholic hepatitis. It points, however, also to the possibility that cirrhosis might develop without significant hepatocellular necrosis and inflammation. Perihepatocellular, periductular, and septal fibrosis are the functionally most important localizations leading to additional hepatic injury. The initiation of these types of fibrosis by liver injury points to a vicious circle. Specific anti-fibroplastic therapy is still in infancy."}
{"id": "PMID:204847", "title": "Inhibition of diacylglycerol:CDPcholine cholinephosphotransferase activity by dimethylaminoethyl p-chlorophenoxyacetate.", "content": "Cholinephosphotransferase [EC 2.7.8.2] activity of rat liver microsomes, with 1,2-di-0-[3H]acyl glycerol or 1-0-hexadecanoyl [U-14C]ethanediol as substrate, was inhibited by N,N-dimethylaminoethyl p-chlorophenoxyacetate (centrophenoxine). Inhibition progressed in a linear fashion with increasing drug levels and was complete at 30 mM concentration. It appears that the microsomal enzyme was largely affected by the drug itself because the hydrolysis products of centrophenoxine, viz., N,N-dimethylaminoethanol and p-chlorophenoxyacetic acid, were less inhibitory.", "contents": "Inhibition of diacylglycerol:CDPcholine cholinephosphotransferase activity by dimethylaminoethyl p-chlorophenoxyacetate. Cholinephosphotransferase [EC 2.7.8.2] activity of rat liver microsomes, with 1,2-di-0-[3H]acyl glycerol or 1-0-hexadecanoyl [U-14C]ethanediol as substrate, was inhibited by N,N-dimethylaminoethyl p-chlorophenoxyacetate (centrophenoxine). Inhibition progressed in a linear fashion with increasing drug levels and was complete at 30 mM concentration. It appears that the microsomal enzyme was largely affected by the drug itself because the hydrolysis products of centrophenoxine, viz., N,N-dimethylaminoethanol and p-chlorophenoxyacetic acid, were less inhibitory."}
{"id": "PMID:204848", "title": "The circadian cycles of plasma corticosterone and adrenal cholesteryl esters in the normal and EFA-deficient female rat.", "content": "In female rats subjected to a 12 hr light-12 hr darkness schedule and fed a semipurified diet containing 10% corn oil, plasma corticosterone concentration showed a monophasic circadian cycle with minimum and maximum concentrations at the start of the light and dark periods, respectively. Adrenal total cholesteryl ester concentration was inversely related to plasma corticosterone, as were those of several of the individual esters; changes in cholesteryl ester concentration appeared to follow rather than precede changes in plasma corticosterone. There was preferential depletion of the cholesteryl esters of 18:1, 18:2omega6, and 20:4omega6 during glucocorticoid secretion. [ EFA, essential fatty acid (s);X:YomegaZ, fatty acid with X carbon atoms and Y olefinic bonds with the terminal double bond Z carbon atoms from the methyl group.] In female rats fed hydrogenated coconut oil (EFA-deficient), a monophasic cycle for plasma corticosterone was also observed, but the peak was much broader than that recorded for rats fed corn oil, although minima and maxima occurred at similar times for the two groups. No significant cycle of adrenal total cholesteryl esters was evident in the deficient rats, but the 20:3omega9 and 22:3omega9 esters did decrease significantly during the period of high plasma corticosterone concentration. Preferential net decreases in adrenal cholesteryl esters during corticosteroidogenesis were more apparent in normal than in EFA-deficient rats.", "contents": "The circadian cycles of plasma corticosterone and adrenal cholesteryl esters in the normal and EFA-deficient female rat. In female rats subjected to a 12 hr light-12 hr darkness schedule and fed a semipurified diet containing 10% corn oil, plasma corticosterone concentration showed a monophasic circadian cycle with minimum and maximum concentrations at the start of the light and dark periods, respectively. Adrenal total cholesteryl ester concentration was inversely related to plasma corticosterone, as were those of several of the individual esters; changes in cholesteryl ester concentration appeared to follow rather than precede changes in plasma corticosterone. There was preferential depletion of the cholesteryl esters of 18:1, 18:2omega6, and 20:4omega6 during glucocorticoid secretion. [ EFA, essential fatty acid (s);X:YomegaZ, fatty acid with X carbon atoms and Y olefinic bonds with the terminal double bond Z carbon atoms from the methyl group.] In female rats fed hydrogenated coconut oil (EFA-deficient), a monophasic cycle for plasma corticosterone was also observed, but the peak was much broader than that recorded for rats fed corn oil, although minima and maxima occurred at similar times for the two groups. No significant cycle of adrenal total cholesteryl esters was evident in the deficient rats, but the 20:3omega9 and 22:3omega9 esters did decrease significantly during the period of high plasma corticosterone concentration. Preferential net decreases in adrenal cholesteryl esters during corticosteroidogenesis were more apparent in normal than in EFA-deficient rats."}
{"id": "PMID:204851", "title": "Metabolism of apolipoprotein A-I in healthy young adults.", "content": "The metabolism of 125I-labeled apolipoprotein A-I bound to high-density lipoproteins by an in vitro transfer procedure was studied in 10 healthy young adults (5 males and 5 females). Both sexes handled the labeled apolipoprotein similarly, and no statistically significant differences were found in the derived kinetic data. The mean (+/- 1 SD) plasma apolipoprotein A-I concentrations (males, 105 +/- 19 mg/dl; females, 111 +/- 13.8 mg/dl) and half-lives (males, 4.46 +/- 0.45 days; females, 4.64 +/- 0.70 days) were similar, as were the fractional rates of catabolism (FCR) of the apoprotein derived from the above data (FCR in males, 27% of intravascular pool/day; FCR in females, 25% of intravascular pool/day). The absolute catabolic rate of the apoprotein, equivalent under steady-state conditions to the synthetic rate, was 12.1 +/- 1.6 mg/kg/day in males and 11.9 +/- 2.4 mg/kg/day in females.", "contents": "Metabolism of apolipoprotein A-I in healthy young adults. The metabolism of 125I-labeled apolipoprotein A-I bound to high-density lipoproteins by an in vitro transfer procedure was studied in 10 healthy young adults (5 males and 5 females). Both sexes handled the labeled apolipoprotein similarly, and no statistically significant differences were found in the derived kinetic data. The mean (+/- 1 SD) plasma apolipoprotein A-I concentrations (males, 105 +/- 19 mg/dl; females, 111 +/- 13.8 mg/dl) and half-lives (males, 4.46 +/- 0.45 days; females, 4.64 +/- 0.70 days) were similar, as were the fractional rates of catabolism (FCR) of the apoprotein derived from the above data (FCR in males, 27% of intravascular pool/day; FCR in females, 25% of intravascular pool/day). The absolute catabolic rate of the apoprotein, equivalent under steady-state conditions to the synthetic rate, was 12.1 +/- 1.6 mg/kg/day in males and 11.9 +/- 2.4 mg/kg/day in females."}
{"id": "PMID:204853", "title": "Regulation of aflatoxin biosynthesis. 1 Comparative study of mycelial composition and glycolysis in aflatoxigen and nonaflatoxigenic strains.", "content": "A comparative biochemical study of an aflatoxigenic strain Aspergillus parasiticus NRRL 3240 and a nonaflatoxigenic strain A. flavus NRRL 3237 was carried out in order to have a better idea of regulation of aflatoxin biosynthesis. The results obtained revealed continuous primary metabolic activity (protein synthesis) in the nonaflatoxigenic strain while the aflatoxigenic stain showed inhibition of protein and nucleic acid synthesis. The aflatoxigenic strain showed higher levels of oxygen uptake, RNA, NAD, FMN and activities of glycolytic enzymes. Furthermore, it had lower of lipids and reduced activity of glucose-6-phosphate dehydrogenase, which is a source for NADPH. The differences observed have been discussed in relation to aflatoxin biosynthesis and its regulation.", "contents": "Regulation of aflatoxin biosynthesis. 1 Comparative study of mycelial composition and glycolysis in aflatoxigen and nonaflatoxigenic strains. A comparative biochemical study of an aflatoxigenic strain Aspergillus parasiticus NRRL 3240 and a nonaflatoxigenic strain A. flavus NRRL 3237 was carried out in order to have a better idea of regulation of aflatoxin biosynthesis. The results obtained revealed continuous primary metabolic activity (protein synthesis) in the nonaflatoxigenic strain while the aflatoxigenic stain showed inhibition of protein and nucleic acid synthesis. The aflatoxigenic strain showed higher levels of oxygen uptake, RNA, NAD, FMN and activities of glycolytic enzymes. Furthermore, it had lower of lipids and reduced activity of glucose-6-phosphate dehydrogenase, which is a source for NADPH. The differences observed have been discussed in relation to aflatoxin biosynthesis and its regulation."}
{"id": "PMID:204854", "title": "Oxygen toxicity: comparative sensitivities of membrane transport, bioenergetics and synthesis in Escherichia coli.", "content": "The oxygen sensitivities of basic cell functions were compared to evaluate their significance as potential causes of the reversible growth inhibition produced in Escherichia coli by exposure to hyperbaric oxygen. Growth and net incorporation of radioactive glucose into cell structure, and specifically in to protein, were completely inhibited in approximately 1/20 of a generation by a gas phase containing 4.2 atmospheres of oxygen. The inhibition occured before there was significant decrement in cellular glucose transport, respiration, or intracellular concentration of adenosine triphosphate. The data indicate that fundamental steps leading to protein biosynthesis from glucose should be examined in the search for specific primary sites of oxygen toxicity.", "contents": "Oxygen toxicity: comparative sensitivities of membrane transport, bioenergetics and synthesis in Escherichia coli. The oxygen sensitivities of basic cell functions were compared to evaluate their significance as potential causes of the reversible growth inhibition produced in Escherichia coli by exposure to hyperbaric oxygen. Growth and net incorporation of radioactive glucose into cell structure, and specifically in to protein, were completely inhibited in approximately 1/20 of a generation by a gas phase containing 4.2 atmospheres of oxygen. The inhibition occured before there was significant decrement in cellular glucose transport, respiration, or intracellular concentration of adenosine triphosphate. The data indicate that fundamental steps leading to protein biosynthesis from glucose should be examined in the search for specific primary sites of oxygen toxicity."}
{"id": "PMID:204857", "title": "[Pancreatitis after renal transplantation (author's transl)].", "content": "A renal transplant patient in whom acute pancreatitis developed 2 1/2 years after surgery is presented. Pancreatisis was accompanied by hyperlipaemia, diabetes mellitus and acute renal failure possibly due to acute tubular necrosis. Pancreatic abscesses necessitated subtotal pancreatectomy 2 months later. Because of generalized tuberculosis finally the patient succumbed 6 weeks thereafter. As aetiological factors cytomegalovirus disease, disorders in lipid metabolism and immunosuppressive therapy must be discussed. It is concluded that prophylactic measures as well as early diagnosis, intensive care and therapy are necessary for reducing the high risks of pancreatis in renal transplant recipients.", "contents": "[Pancreatitis after renal transplantation (author's transl)]. A renal transplant patient in whom acute pancreatitis developed 2 1/2 years after surgery is presented. Pancreatisis was accompanied by hyperlipaemia, diabetes mellitus and acute renal failure possibly due to acute tubular necrosis. Pancreatic abscesses necessitated subtotal pancreatectomy 2 months later. Because of generalized tuberculosis finally the patient succumbed 6 weeks thereafter. As aetiological factors cytomegalovirus disease, disorders in lipid metabolism and immunosuppressive therapy must be discussed. It is concluded that prophylactic measures as well as early diagnosis, intensive care and therapy are necessary for reducing the high risks of pancreatis in renal transplant recipients."}
{"id": "PMID:204855", "title": "Is the polio virus responsible for late central nervous system tumors?", "content": "A hypothesis is advanced concerning the relationship of poliomyelitis viruses and late developing neoplasia in the central nervous system. The literature is surveyed, and several experimental approaches based upon known evidence of viral and neoplastic behaviour are advanced. The present status of world polio incidence is discussed as it applies to this possible relationship.", "contents": "Is the polio virus responsible for late central nervous system tumors? A hypothesis is advanced concerning the relationship of poliomyelitis viruses and late developing neoplasia in the central nervous system. The literature is surveyed, and several experimental approaches based upon known evidence of viral and neoplastic behaviour are advanced. The present status of world polio incidence is discussed as it applies to this possible relationship."}
{"id": "PMID:204861", "title": "Regulation of the deo operon in Escherichia coli: the double negative control of the deo operon by the cytR and deoR repressors in a DNA directed in vitro system.", "content": "The synthesis of the four enzymes of the deo operon in Escherichia coli is known from in vivo experiments to be subject to a double negative control, exerted by the products of the cytR and deoR genes. A DNA-directed in vitro protein synthesizing system makes the deo enzymes (exemplified by thymidine phosphorylase) in agreement with in vivo results. Enzyme synthesis is stimulated by cyclic AMP and repressed by the cytR and deoR gene products. Repression by the cytR repressor is reversed by cytidine or adenosine in the presence of cyclic AMP, while repression by the deoR repressor is reversed by deoxyribose-5-phosphate. Assays for the presence of the cytR and deoR repressors were established by use of S-30 extracts prepared from the regulatory mutants. Dissociation constants for repressor-operator binding as well as for repressor-inducer interactions have been estimated from the results.", "contents": "Regulation of the deo operon in Escherichia coli: the double negative control of the deo operon by the cytR and deoR repressors in a DNA directed in vitro system. The synthesis of the four enzymes of the deo operon in Escherichia coli is known from in vivo experiments to be subject to a double negative control, exerted by the products of the cytR and deoR genes. A DNA-directed in vitro protein synthesizing system makes the deo enzymes (exemplified by thymidine phosphorylase) in agreement with in vivo results. Enzyme synthesis is stimulated by cyclic AMP and repressed by the cytR and deoR gene products. Repression by the cytR repressor is reversed by cytidine or adenosine in the presence of cyclic AMP, while repression by the deoR repressor is reversed by deoxyribose-5-phosphate. Assays for the presence of the cytR and deoR repressors were established by use of S-30 extracts prepared from the regulatory mutants. Dissociation constants for repressor-operator binding as well as for repressor-inducer interactions have been estimated from the results."}
{"id": "PMID:204862", "title": "A yeast mutant with glucose-resistant formation of mitochondrial enzymes.", "content": "Yeast mutants with glucose-insensitive formation of mitochondrial enzymes were isolated starting with a strain completely lacking alcohol dehydrogenase activity. The mutations could uniquely be attributed to a single nuclear gene, designated CCR80. They were largely dominant. Glucose-resistant enzyme formation was most prominent with regard to mitochondrial enzymes succinate dehydrogenase and NADH: cytochrome c oxidoreductase. The effect of CCR80r mutations was rather small but significant on the gluconeogenetic enzymes isocitrate lyase, malate synthase and fructose-1,6-bisphosphatase and on invertase synthesis. The repressive effect of maltose in CCR80r mutants was also reduced showing that glucose-resistance is not caused by a mere hexose uptake defect. This regulatory disorders were not accompanied by reduced levels of glycolytic enzymes or drastically altered levels of glycolytic intermediates. Aerobic fermentation of glucose was almost completely inhibited in the mutants; anaerobic glucose degradation was reduced but not completely abolished. Therefore, the mutants appear to be altered in the regulation of glycolysis. A largely glucose-resistant synthesis of respiratory enzymes is obviously a corollary of this alteration.", "contents": "A yeast mutant with glucose-resistant formation of mitochondrial enzymes. Yeast mutants with glucose-insensitive formation of mitochondrial enzymes were isolated starting with a strain completely lacking alcohol dehydrogenase activity. The mutations could uniquely be attributed to a single nuclear gene, designated CCR80. They were largely dominant. Glucose-resistant enzyme formation was most prominent with regard to mitochondrial enzymes succinate dehydrogenase and NADH: cytochrome c oxidoreductase. The effect of CCR80r mutations was rather small but significant on the gluconeogenetic enzymes isocitrate lyase, malate synthase and fructose-1,6-bisphosphatase and on invertase synthesis. The repressive effect of maltose in CCR80r mutants was also reduced showing that glucose-resistance is not caused by a mere hexose uptake defect. This regulatory disorders were not accompanied by reduced levels of glycolytic enzymes or drastically altered levels of glycolytic intermediates. Aerobic fermentation of glucose was almost completely inhibited in the mutants; anaerobic glucose degradation was reduced but not completely abolished. Therefore, the mutants appear to be altered in the regulation of glycolysis. A largely glucose-resistant synthesis of respiratory enzymes is obviously a corollary of this alteration."}
{"id": "PMID:204863", "title": "[Effect of oxidizing and reducing agents on the rate of water proton relaxation in the chloroplasts of beans and particles of photosystem 2].", "content": "The change of longitudinal proton relaxation rate, 1/T1, in the native and shocked chloroplasts, PS2 chloroplasts' particles and exogenous complexes Mn2+--PPCI (pigment--protein complex of PSI), Mn2+--PPCII in the presence of the PS2 donors and acceptors and at different pH change were studied. It has been shown that 1/T1 increases in chloroplasts and PS2 particles in the presence of the PS2 donors and decreases in the presence of the acceptors in contrast to untreated preparations. The 1/T1 change of exogenous complexes is not specific. The results suggest that the manganese pool of the chloroplasts PS2 may be the main factor responsible for the chloroplasts' proton relaxation rate. The change of the manganese valency in the presence of donors and of acceptors may result in changing 1/T1.", "contents": "[Effect of oxidizing and reducing agents on the rate of water proton relaxation in the chloroplasts of beans and particles of photosystem 2]. The change of longitudinal proton relaxation rate, 1/T1, in the native and shocked chloroplasts, PS2 chloroplasts' particles and exogenous complexes Mn2+--PPCI (pigment--protein complex of PSI), Mn2+--PPCII in the presence of the PS2 donors and acceptors and at different pH change were studied. It has been shown that 1/T1 increases in chloroplasts and PS2 particles in the presence of the PS2 donors and decreases in the presence of the acceptors in contrast to untreated preparations. The 1/T1 change of exogenous complexes is not specific. The results suggest that the manganese pool of the chloroplasts PS2 may be the main factor responsible for the chloroplasts' proton relaxation rate. The change of the manganese valency in the presence of donors and of acceptors may result in changing 1/T1."}
{"id": "PMID:204864", "title": "[Effect of low-molecular nuclear RNA on RNA synthesis in isolated nuclei].", "content": "An attempt was made to elucidate possible participation of low molecular weight nuclear RNA's (LMWN RNA's) in the transcription process. For this purpose, we studied the effect of individual fractions of LMWN RNA's, isolated by polyacrylamide gel electrophoresis, on the endogenous RNA synthesis in isolated nuclei. We have found no influence of LMWN RNA's on the incorporation of labeled precursors in the acid-insoluble material under the conditions when RNA polymerase I is predominantly active. The results obtained thus indicate that LMWN RNA's do not participate in the regulation of 45S pre-rRNA synthesis and they do not belong to limiting factors in pre-rRNA synthesis.", "contents": "[Effect of low-molecular nuclear RNA on RNA synthesis in isolated nuclei]. An attempt was made to elucidate possible participation of low molecular weight nuclear RNA's (LMWN RNA's) in the transcription process. For this purpose, we studied the effect of individual fractions of LMWN RNA's, isolated by polyacrylamide gel electrophoresis, on the endogenous RNA synthesis in isolated nuclei. We have found no influence of LMWN RNA's on the incorporation of labeled precursors in the acid-insoluble material under the conditions when RNA polymerase I is predominantly active. The results obtained thus indicate that LMWN RNA's do not participate in the regulation of 45S pre-rRNA synthesis and they do not belong to limiting factors in pre-rRNA synthesis."}
{"id": "PMID:204868", "title": "Cellular reactivity to altered glomerular basement membrane in glomerulonephritis.", "content": "Glomerular basement membrane may be altered during glomerulonephritis, exposing antigens that are recognized as foreign. Immunochemical studies suggest that removal of peripheral glycopeptides from the basement membrane with glycosidase mimics this pathogenetic event. To examine these hypotheses, we studied 24 patients with biopsy-proved glomerulonephritis by means of the lymphocyte-blast-transformation assay. Three preparations of normal glomerular basement membrane were used: two mimicked the native state for the peripheral glycopeptides, and one was altered by glycosidases. Results showed minimal differences in responses to native glomerular basement-membrane preparations among patients with glomerulonephritis and control groups. However, patients with glomerulonephritis had a significant blastogenic response to the glycosidase-treated glomerular basement membrane as compared to patients with nonglomerular renal disease and normal controls (P less than 0.0005). These studies suggest that cellular reactivity to altered glomerular basement-membrane antigens can be detected in certain forms of progressive glomerulonephritis.", "contents": "Cellular reactivity to altered glomerular basement membrane in glomerulonephritis. Glomerular basement membrane may be altered during glomerulonephritis, exposing antigens that are recognized as foreign. Immunochemical studies suggest that removal of peripheral glycopeptides from the basement membrane with glycosidase mimics this pathogenetic event. To examine these hypotheses, we studied 24 patients with biopsy-proved glomerulonephritis by means of the lymphocyte-blast-transformation assay. Three preparations of normal glomerular basement membrane were used: two mimicked the native state for the peripheral glycopeptides, and one was altered by glycosidases. Results showed minimal differences in responses to native glomerular basement-membrane preparations among patients with glomerulonephritis and control groups. However, patients with glomerulonephritis had a significant blastogenic response to the glycosidase-treated glomerular basement membrane as compared to patients with nonglomerular renal disease and normal controls (P less than 0.0005). These studies suggest that cellular reactivity to altered glomerular basement-membrane antigens can be detected in certain forms of progressive glomerulonephritis."}
{"id": "PMID:204866", "title": "Lymphoid changes suggesting escalation of immune response into malignant lymphoma.", "content": "The conditions in which the microscopic changes of the lymphoid organs, especially lymph nodes, render difficult the histologic decision of immune response or malignant lymphoma, are reviewed. The possibility that in certain circumstances, prolonged, pathologic immune response escalate to malignant lymphomas, as well as the new classifications of these diseases, in terms of this conception are discussed.", "contents": "Lymphoid changes suggesting escalation of immune response into malignant lymphoma. The conditions in which the microscopic changes of the lymphoid organs, especially lymph nodes, render difficult the histologic decision of immune response or malignant lymphoma, are reviewed. The possibility that in certain circumstances, prolonged, pathologic immune response escalate to malignant lymphomas, as well as the new classifications of these diseases, in terms of this conception are discussed."}
{"id": "PMID:204878", "title": "Behavior of mitochondria from normal and tumor cells in isopycnic sucrose gradients.", "content": "Rat and mouse liver mitochondria, when centrifuged in a sucrose density gradient (25--50%, w/w), showed the presence of heavy (H) and light (L) subfractions with buoyant densities 1.185 and 1.170--1.165 g/ml, respectively. Mild treatment with digitonin or EDTA (30 mM) shifted H-subfraction of mitochondria into the lighter zone of the gradient and as a result of this the mitochondria were distributed as a homogenous band with buoyant density 1.170--1.165 g/ml. Mitochondria isolated from both MD hepatoma and Zajdela rat hepatoma were characterized by a homogenous banding with buoyant density 1.160--1.165 g/ml. Regarding to this, the content and patterns of polyribosomes bound to outer membranes of mouse tumor mitochondria were studied. Analysis of polyribosomes as well as the results of RNA polyacrylamide gel electrophoresis indicate that the content of these polyribosomes in tumor mitochondria is less than that in normal liver ones. However, the decrease of cancer cell membrane-bound polyribosomes cannot account for the differences in buoyant densities of mitochondria from normal and tumor tissues.", "contents": "Behavior of mitochondria from normal and tumor cells in isopycnic sucrose gradients. Rat and mouse liver mitochondria, when centrifuged in a sucrose density gradient (25--50%, w/w), showed the presence of heavy (H) and light (L) subfractions with buoyant densities 1.185 and 1.170--1.165 g/ml, respectively. Mild treatment with digitonin or EDTA (30 mM) shifted H-subfraction of mitochondria into the lighter zone of the gradient and as a result of this the mitochondria were distributed as a homogenous band with buoyant density 1.170--1.165 g/ml. Mitochondria isolated from both MD hepatoma and Zajdela rat hepatoma were characterized by a homogenous banding with buoyant density 1.160--1.165 g/ml. Regarding to this, the content and patterns of polyribosomes bound to outer membranes of mouse tumor mitochondria were studied. Analysis of polyribosomes as well as the results of RNA polyacrylamide gel electrophoresis indicate that the content of these polyribosomes in tumor mitochondria is less than that in normal liver ones. However, the decrease of cancer cell membrane-bound polyribosomes cannot account for the differences in buoyant densities of mitochondria from normal and tumor tissues."}
{"id": "PMID:204879", "title": "The effect of psychotropic drugs on the TSH-response to thyroliberin (TRH).", "content": "The effect of chlorpromazine (CPZ), thioridazine (TR), L-dopa, fusaric acid (FA), pimozide (PZ) and propranolol (P) in the i.v. thyrotropin-releasing hormone (TRH) stimulation test was studied in 75 subjects. It was found that chronic treatment with CPZ, TR and L-dopa inhibits the response to TRH. FA may to some extent counteract the effect of L-dopa. The results indicate that the response of the pituitary to TRH as regards the secretion of TSH is mainly regulated by norepinephrinergic alpha-receptors.", "contents": "The effect of psychotropic drugs on the TSH-response to thyroliberin (TRH). The effect of chlorpromazine (CPZ), thioridazine (TR), L-dopa, fusaric acid (FA), pimozide (PZ) and propranolol (P) in the i.v. thyrotropin-releasing hormone (TRH) stimulation test was studied in 75 subjects. It was found that chronic treatment with CPZ, TR and L-dopa inhibits the response to TRH. FA may to some extent counteract the effect of L-dopa. The results indicate that the response of the pituitary to TRH as regards the secretion of TSH is mainly regulated by norepinephrinergic alpha-receptors."}
{"id": "PMID:204880", "title": "Growth hormone and ACTH in the pituitary of normal and anencephalic human fetuses: immunocytochemical evidence for hypothalamic influences during development.", "content": "The influence of the hypothalamus on the development of the anterior pituitary cells was studied in normal and anencaphalic human fetuses. An immunocytological method was applied to study the quantitative evolution of the size of the cells during gestation. The somatotropic and corticotropic cells appeared at the end of the 2nd month of gestation. After the 3rd month of gestation their normal development required the presence of brain. The results suggest that hypothalamic factors are needed for the normal development of cells containing these pituitary hormones.", "contents": "Growth hormone and ACTH in the pituitary of normal and anencephalic human fetuses: immunocytochemical evidence for hypothalamic influences during development. The influence of the hypothalamus on the development of the anterior pituitary cells was studied in normal and anencaphalic human fetuses. An immunocytological method was applied to study the quantitative evolution of the size of the cells during gestation. The somatotropic and corticotropic cells appeared at the end of the 2nd month of gestation. After the 3rd month of gestation their normal development required the presence of brain. The results suggest that hypothalamic factors are needed for the normal development of cells containing these pituitary hormones."}
{"id": "PMID:204881", "title": "Thyrotropin-releasing hormone does not alter the release of melanocyte-stimulating hormone or adrenocorticotropic hormone from the rat pars intermedia.", "content": "Thyrotropin-releasing hormone (TRH) has been reported to stimulate the release of melanocyte-stimulating hormone (MSH) from the pars intermedia (PI) of Rana esculenta. To test its effect on the rat PI, acutely dispersed rat PI cells, as well as whole nervosa-intermedias (NI), were incubated with synthetic TRH, from 10(--10)--10(--4)M. TRH did not alter the release of either MSH or adrenocorticotropic hormone (ACTH).", "contents": "Thyrotropin-releasing hormone does not alter the release of melanocyte-stimulating hormone or adrenocorticotropic hormone from the rat pars intermedia. Thyrotropin-releasing hormone (TRH) has been reported to stimulate the release of melanocyte-stimulating hormone (MSH) from the pars intermedia (PI) of Rana esculenta. To test its effect on the rat PI, acutely dispersed rat PI cells, as well as whole nervosa-intermedias (NI), were incubated with synthetic TRH, from 10(--10)--10(--4)M. TRH did not alter the release of either MSH or adrenocorticotropic hormone (ACTH)."}
{"id": "PMID:204882", "title": "Computed tomographic evaluation of therapeutically induced changes in primary and secondary brain tumors.", "content": "A prospective study was initiated to evaluate computed tomography as a method for monitoring therapeutically induced changes in brain tumors. Early postoperative scans may be misleading in the evaluation of residual tumor because of trauma to the blood-brain barrier during operation. The size of the dominant mass (17/25), enhancement (11/25), edema (11/25), and ventricular distortion (14/25) were decreased in many patients after radiation therapy. Occasional tumors increased in size during radiation therapy (3/25). Enlargement of the lateral ventricles developed in 9 of 25 patients. Computed tomography offers definite advantages over nuclide brain scans, angiography and other diagnostic studies for evaluating therapeutically induced changes in brain tumors.", "contents": "Computed tomographic evaluation of therapeutically induced changes in primary and secondary brain tumors. A prospective study was initiated to evaluate computed tomography as a method for monitoring therapeutically induced changes in brain tumors. Early postoperative scans may be misleading in the evaluation of residual tumor because of trauma to the blood-brain barrier during operation. The size of the dominant mass (17/25), enhancement (11/25), edema (11/25), and ventricular distortion (14/25) were decreased in many patients after radiation therapy. Occasional tumors increased in size during radiation therapy (3/25). Enlargement of the lateral ventricles developed in 9 of 25 patients. Computed tomography offers definite advantages over nuclide brain scans, angiography and other diagnostic studies for evaluating therapeutically induced changes in brain tumors."}
{"id": "PMID:204891", "title": "Malignant fibrohistocytoma of the maxilla presenting with endodotically involved teeth.", "content": "It is well established that a periapical lesion may be the first presenting form of more serious disease. A case of malignant fibrohistocytoma has been presented. It is of special interest because of the rarity of the disease, especially in the jaws, and because it presented as periapical disease associated with nonvital teeth. The case emphasizes the value of routine histopathologic examination of tissue and the need for maintaining a high \"index of suspicion\" when dealing with clinically atypical behavior. The value of consultation with an oral pathologist has also been stressed.", "contents": "Malignant fibrohistocytoma of the maxilla presenting with endodotically involved teeth. It is well established that a periapical lesion may be the first presenting form of more serious disease. A case of malignant fibrohistocytoma has been presented. It is of special interest because of the rarity of the disease, especially in the jaws, and because it presented as periapical disease associated with nonvital teeth. The case emphasizes the value of routine histopathologic examination of tissue and the need for maintaining a high \"index of suspicion\" when dealing with clinically atypical behavior. The value of consultation with an oral pathologist has also been stressed."}
{"id": "PMID:204899", "title": "The role of antibiotics, immunizations, and adenoviruses in pertussis.", "content": "Sixty-five patients with pertussis were identified by a clinical criterion, and Bordetella pertussis was isolated from 75% of these patients or their symptomatic household contacts. Negative nasopharyngeal cultures were usually associated with either a history of antibiotic therapy with erythromycin or tetracycline (two of three patients), two or more diphtheria and tetanus toxoids with pertussis (DTP) vaccines (six of eight patients), or both (two of three patients). Erythromycin therapy resulted in the elimination of B. pertussis from the nasopharynx in 2 to 7 days (mean, 3.6 days) compared with 7 to 17 or more days (mean, greater than 12 days) in patients treated with no antibiotics, but had no effect on the duration or severity of illness as judged by length of hospitalization. Adenoviruses were recovered from five of 44 patients cultured. Four of these isolates were from throat swabs obtained early in the illness and the remaining isolate was from one of 33 repeated viral cultures obtained two to three weeks later; B. pertussis was also isolated from these five patients. Paired serum samples were obtained from only two of these patients. Neither demonstrated a fourfold rise in adenoviral complement-fixing antibodies. Therefore, in these patients, adenoviral isolation may have been secondary to reactivation of a latent viral infection by infection with B. pertussis.", "contents": "The role of antibiotics, immunizations, and adenoviruses in pertussis. Sixty-five patients with pertussis were identified by a clinical criterion, and Bordetella pertussis was isolated from 75% of these patients or their symptomatic household contacts. Negative nasopharyngeal cultures were usually associated with either a history of antibiotic therapy with erythromycin or tetracycline (two of three patients), two or more diphtheria and tetanus toxoids with pertussis (DTP) vaccines (six of eight patients), or both (two of three patients). Erythromycin therapy resulted in the elimination of B. pertussis from the nasopharynx in 2 to 7 days (mean, 3.6 days) compared with 7 to 17 or more days (mean, greater than 12 days) in patients treated with no antibiotics, but had no effect on the duration or severity of illness as judged by length of hospitalization. Adenoviruses were recovered from five of 44 patients cultured. Four of these isolates were from throat swabs obtained early in the illness and the remaining isolate was from one of 33 repeated viral cultures obtained two to three weeks later; B. pertussis was also isolated from these five patients. Paired serum samples were obtained from only two of these patients. Neither demonstrated a fourfold rise in adenoviral complement-fixing antibodies. Therefore, in these patients, adenoviral isolation may have been secondary to reactivation of a latent viral infection by infection with B. pertussis."}
{"id": "PMID:204900", "title": "Adenovirus meningoencephalitis.", "content": "Central nervous system manifestations in association with adenovirus infections have rarely been documented. In this report, four children, ages 4, 5, 6, and 10 years, with adenoviral meningoencephalitis are described. Adenoviruses were recovered from CSF specimens in all four patients.", "contents": "Adenovirus meningoencephalitis. Central nervous system manifestations in association with adenovirus infections have rarely been documented. In this report, four children, ages 4, 5, 6, and 10 years, with adenoviral meningoencephalitis are described. Adenoviruses were recovered from CSF specimens in all four patients."}
{"id": "PMID:204904", "title": "Inability of myoglobin to increase in dystrophic skeletal muscle during daily exercise.", "content": "An exercise program consisting of 80-min daily runs on a treadmill was performed by normal and dystrophic hamsters. Subgroups were sacrificed at various times during the 45-day program. Daily exercise resulted in a significant increase in the myoglobin concentration of gastrocnemius muscles in normal animals but not in dystrophic animals. In the exercise groups of hamsters, there were significant increases in the concentration of cytochrome c, a marker for respiratory capacity, in the gastrocnemius of both normal and dystrophic hamsters.", "contents": "Inability of myoglobin to increase in dystrophic skeletal muscle during daily exercise. An exercise program consisting of 80-min daily runs on a treadmill was performed by normal and dystrophic hamsters. Subgroups were sacrificed at various times during the 45-day program. Daily exercise resulted in a significant increase in the myoglobin concentration of gastrocnemius muscles in normal animals but not in dystrophic animals. In the exercise groups of hamsters, there were significant increases in the concentration of cytochrome c, a marker for respiratory capacity, in the gastrocnemius of both normal and dystrophic hamsters."}
{"id": "PMID:204905", "title": "The sensitivity of pineal gland beta-receptors appears to be dependent upon calcium ions.", "content": "Rat pineals were used in vitro to demonstrate that calcium antagonists induce a hyposensitive response to stimulation of serotonin N-acetyl transferase (NAT) by the beta-agonist isoproterenol or by dibutyryl cyclic AMP. Mn2+, Co2+ and La3+ at 10(-3)M all significantly reduce the effects of isoproterenol stimulation. In addition, the two enantiomers of D600 also inhibit NAT induction, the D-form slightly more effectively than the L-form. Interestingly, La3+ is also able to inhibit NAT after DBcAMP, indicating that Ca2+ can also control enzyme induction at an intracellular site beyond the beta-receptor.", "contents": "The sensitivity of pineal gland beta-receptors appears to be dependent upon calcium ions. Rat pineals were used in vitro to demonstrate that calcium antagonists induce a hyposensitive response to stimulation of serotonin N-acetyl transferase (NAT) by the beta-agonist isoproterenol or by dibutyryl cyclic AMP. Mn2+, Co2+ and La3+ at 10(-3)M all significantly reduce the effects of isoproterenol stimulation. In addition, the two enantiomers of D600 also inhibit NAT induction, the D-form slightly more effectively than the L-form. Interestingly, La3+ is also able to inhibit NAT after DBcAMP, indicating that Ca2+ can also control enzyme induction at an intracellular site beyond the beta-receptor."}
{"id": "PMID:204906", "title": "A study of the interaction of catecholamines and antidiuretic hormone on water permeability and the cyclic AMP system in isolated papillae of the rat.", "content": "The diffusional water permeability of collecting ducts in vitro and the cyclic A.M.P. content of isolated papillae were measured after exposure to different concentrations of antidiuretic hormone, isoproterenol and noradrenalin. Antidiuretic hormone 25 mu units/ml. caused a 25% increase in diffusional water permeability. This response was not affected by isoproterenol (10(-6) M) or noradrenalin (2 x 10(-6) M). Antidiuretic hormone 100 mu unit ml-1 caused a 50% increase in diffusional water permeability which likewise was not altered by isoproterenol or noradrenalin. Isoproterenol (10(-6) M) and noradrenalin (2 x 10(-6) M) had no significant effect on basal levels of diffusional water permeability. Isoproterenol had no significant effect on the tissue concentration of cyclic A.M.P. concentration induced by antidiuretic hormone. Noradrenalin (2 x 10(-6) and 10(-4)) had no significant effect on basal cyclic A.M.P. concentration. However, noradrenalin inhibited the stimulation of cyclic A.M.P. induced by antidiuretic hormone. This effect was inhibited by phentolamine. This study suggests that catecholamines do not alter water handling by a direct action on the water permeability of the kidney but probably exert their action through an effect of A.D.H. release.", "contents": "A study of the interaction of catecholamines and antidiuretic hormone on water permeability and the cyclic AMP system in isolated papillae of the rat. The diffusional water permeability of collecting ducts in vitro and the cyclic A.M.P. content of isolated papillae were measured after exposure to different concentrations of antidiuretic hormone, isoproterenol and noradrenalin. Antidiuretic hormone 25 mu units/ml. caused a 25% increase in diffusional water permeability. This response was not affected by isoproterenol (10(-6) M) or noradrenalin (2 x 10(-6) M). Antidiuretic hormone 100 mu unit ml-1 caused a 50% increase in diffusional water permeability which likewise was not altered by isoproterenol or noradrenalin. Isoproterenol (10(-6) M) and noradrenalin (2 x 10(-6) M) had no significant effect on basal levels of diffusional water permeability. Isoproterenol had no significant effect on the tissue concentration of cyclic A.M.P. concentration induced by antidiuretic hormone. Noradrenalin (2 x 10(-6) and 10(-4)) had no significant effect on basal cyclic A.M.P. concentration. However, noradrenalin inhibited the stimulation of cyclic A.M.P. induced by antidiuretic hormone. This effect was inhibited by phentolamine. This study suggests that catecholamines do not alter water handling by a direct action on the water permeability of the kidney but probably exert their action through an effect of A.D.H. release."}
{"id": "PMID:204908", "title": "The prophylactic use of vitamin D3 in parturient paresis in the cow in a practice district in eastern Norway. A retrospective investigation.", "content": "The prophylactic effect in parturient paresis of an intramuscular injection of 10 million i.u. vitamin D3 one week prior to the expected calving date, was investigated in 84 cows which had previously suffered from parturient paresis. Clinical observations in connection with the development of parturient paresis after injection of vitamin D3 were compared with corresponding observations made on cows within the same population at the previous calving when no vitamin D3 was administered. The incidence of clinical parturient paresis in cows given vitamin D3 was 44.3 per cent. There were no significant differences in the incidence of parturient paresis in cows injected with vitamin D3 during the periods less than 2, 2--4, 5--8 and greater than 8 days before parturition. Average plasma calcium levels (mg/100 ml) before first calcium treatment, results of treatment, and the incidence of retained placenta in vitamin D3 injected cows did not differ significantly from corresponding data for cows with clinical parturient paresis which had not been given vitamin D3 before calving. It is concluded that vitamin D3 does not have any prophylactic effect in parturient paresis in cows in Eastern Norway.", "contents": "The prophylactic use of vitamin D3 in parturient paresis in the cow in a practice district in eastern Norway. A retrospective investigation. The prophylactic effect in parturient paresis of an intramuscular injection of 10 million i.u. vitamin D3 one week prior to the expected calving date, was investigated in 84 cows which had previously suffered from parturient paresis. Clinical observations in connection with the development of parturient paresis after injection of vitamin D3 were compared with corresponding observations made on cows within the same population at the previous calving when no vitamin D3 was administered. The incidence of clinical parturient paresis in cows given vitamin D3 was 44.3 per cent. There were no significant differences in the incidence of parturient paresis in cows injected with vitamin D3 during the periods less than 2, 2--4, 5--8 and greater than 8 days before parturition. Average plasma calcium levels (mg/100 ml) before first calcium treatment, results of treatment, and the incidence of retained placenta in vitamin D3 injected cows did not differ significantly from corresponding data for cows with clinical parturient paresis which had not been given vitamin D3 before calving. It is concluded that vitamin D3 does not have any prophylactic effect in parturient paresis in cows in Eastern Norway."}
{"id": "PMID:204910", "title": "Gene mapping and gene enrichment by the avidin-biotin interaction: use of cytochrome-c as a polyamine bridge.", "content": "A modification of previously described methods of electron microscopic gene mapping and of gene enrichment based on the avidin-biotin interaction is presented. The modification consists of coupling cytochrome-c instead of pentane diamine to the oxidized 2', 3' terminus of an RNA by Schiff base formation and BH-4 reduction. The RNA-cytochrome-c conjugate is purified by a simple chromatographic procedure; several biotins are attached to the cytochrome moiety by acylation. The extended arm between biotin and RNA gives efficient electron microscopic gene mapping of DNA:RNA-biotin hybrids with avidin-ferritin and avidin-polymethacylate sphere labels and efficient gene enrichment by buoyant banding of DNA:RNA-biotin:avidin-spheres in CsCl. A 1400 fold enrichment (thus, 25% pure) and a 90% yield of long Drosophila DNA strands with 5S RNA genes is achieved.", "contents": "Gene mapping and gene enrichment by the avidin-biotin interaction: use of cytochrome-c as a polyamine bridge. A modification of previously described methods of electron microscopic gene mapping and of gene enrichment based on the avidin-biotin interaction is presented. The modification consists of coupling cytochrome-c instead of pentane diamine to the oxidized 2', 3' terminus of an RNA by Schiff base formation and BH-4 reduction. The RNA-cytochrome-c conjugate is purified by a simple chromatographic procedure; several biotins are attached to the cytochrome moiety by acylation. The extended arm between biotin and RNA gives efficient electron microscopic gene mapping of DNA:RNA-biotin hybrids with avidin-ferritin and avidin-polymethacylate sphere labels and efficient gene enrichment by buoyant banding of DNA:RNA-biotin:avidin-spheres in CsCl. A 1400 fold enrichment (thus, 25% pure) and a 90% yield of long Drosophila DNA strands with 5S RNA genes is achieved."}
{"id": "PMID:204911", "title": "Base-specific reactions useful for DNA sequencing: methylene blue--sensitized photooxidation of guanine and osmium tetraoxide modification of thymine.", "content": "Exposure of DNA to methylene blue and visible or ultraviolet light causes guanine-specific modification, and subsequent treatment with piperidine leads to chain cleavage at each guanine residue. Treatment of DNA with osmium tetraoxide in dilute pyridine leads to thymidine-specific modification, and subsequent treatment with piperidine leads to chain cleavage at the modified thymidine residues. Both reactions can be used in conjunction with other base specific modifications described by Maxam and Gilbert (1) for the determination of the nucleotide sequence in DNA.", "contents": "Base-specific reactions useful for DNA sequencing: methylene blue--sensitized photooxidation of guanine and osmium tetraoxide modification of thymine. Exposure of DNA to methylene blue and visible or ultraviolet light causes guanine-specific modification, and subsequent treatment with piperidine leads to chain cleavage at each guanine residue. Treatment of DNA with osmium tetraoxide in dilute pyridine leads to thymidine-specific modification, and subsequent treatment with piperidine leads to chain cleavage at the modified thymidine residues. Both reactions can be used in conjunction with other base specific modifications described by Maxam and Gilbert (1) for the determination of the nucleotide sequence in DNA."}
{"id": "PMID:204912", "title": "Interaction of the DNA untwisting enzyme with the SV40 nucleoprotein complex.", "content": "The SV40 nucleoprotein complex which was isolated from infected CV-1 cells did not possess an active DNA untwisting enzyme. The superhelix density of the DNA in the chromatin complex was unchanged after treatment with purified rat liver DNA untwisting enzyme. However, in the presence of ethidium bromide (1 microgram/ml) the superhelix density was changed. Moreover, the nicked intermediate in the DNA untwisting reaction could be detected using the chromatin DNA as a substrate. These results show that the DNA in the SV40 chromatin which is accessible to the DNA untwisting enzyme is under no topological strain.", "contents": "Interaction of the DNA untwisting enzyme with the SV40 nucleoprotein complex. The SV40 nucleoprotein complex which was isolated from infected CV-1 cells did not possess an active DNA untwisting enzyme. The superhelix density of the DNA in the chromatin complex was unchanged after treatment with purified rat liver DNA untwisting enzyme. However, in the presence of ethidium bromide (1 microgram/ml) the superhelix density was changed. Moreover, the nicked intermediate in the DNA untwisting reaction could be detected using the chromatin DNA as a substrate. These results show that the DNA in the SV40 chromatin which is accessible to the DNA untwisting enzyme is under no topological strain."}
{"id": "PMID:204915", "title": "Cytomegalovirus infection and the Guillain-Barr\u00e9 syndrome.", "content": "A fatal case is described of the Guillain-Barr\u00e9 syndrome due to cytomegalovirus infection, which was associated with hepatitis, myocarditis and viral pneumonia. Previous cases, which have usually run a benign course, are reviewed. Attention is drawn to the possible adverse effect of steroid therapy.", "contents": "Cytomegalovirus infection and the Guillain-Barr\u00e9 syndrome. A fatal case is described of the Guillain-Barr\u00e9 syndrome due to cytomegalovirus infection, which was associated with hepatitis, myocarditis and viral pneumonia. Previous cases, which have usually run a benign course, are reviewed. Attention is drawn to the possible adverse effect of steroid therapy."}
{"id": "PMID:204918", "title": "[Cytochrome oxidase activity in diabetes mellitus].", "content": "The results of study of the activity of cytochromeoxidase in the blood formed elements in 84 patients suffering from diabetes mellitus before and after the treatment are presented. In patients with the primarily detected disease the activity of the enzyme was reduced, and in its prolonged course--it was elevated. A tendency to normalization of the enzyme activity was noted as a result of treatment in all the forms of the course of the disease; however, the interstitial metabolism failed to become restored completely.", "contents": "[Cytochrome oxidase activity in diabetes mellitus]. The results of study of the activity of cytochromeoxidase in the blood formed elements in 84 patients suffering from diabetes mellitus before and after the treatment are presented. In patients with the primarily detected disease the activity of the enzyme was reduced, and in its prolonged course--it was elevated. A tendency to normalization of the enzyme activity was noted as a result of treatment in all the forms of the course of the disease; however, the interstitial metabolism failed to become restored completely."}
{"id": "PMID:204919", "title": "[Various mechanisms of disorders of the hypothalamo-hypophyseal-adrenal system in Cushing's syndrome].", "content": "The authors present the results of study of corticotropine and cortizol secretion under the effect of stress caused by insulin hypoglycemia, of sensitivity of the adrenal glands to the administration of exogenous synthetic corticotropine, and of the 24-hour rhythm of the corticotropine and cortizol secretion in 26 healthy persons and in 57 patients suffering from Itsenko-Cushing's disease, including 25 after a course of treatment with chloditan, an inhibitor of the adrenal cortex function. Blood corticotropine content was determined by the radioimmunological method, and of cortizol--by competitive binding. There was revealed no significant increase of corticotropine and cortizol secretion in response to insulin hypoglycemia in Itsenko-Cushing's disease, this pointing to disturbance of the hypothalamo-hypophysio-adrenal system at the hypothalamic level. No qualitative differences were found in response of the adrenal cortex to corticotropine, this indicating the absence of changes of its sensitivity to this hormone. The 24-hour rhythm of corticotropine and cortizol secretion in this disease is inverted. At the immediate periods after chloditan treatment no normalization of the response of the adrenal cortex to insulin hypoglycemia, and of the 24-hour rhythm of corticotropine and cortizol secretion, and also of the changes in the adrenal cortex sensitivity to corticotropine was seen.", "contents": "[Various mechanisms of disorders of the hypothalamo-hypophyseal-adrenal system in Cushing's syndrome]. The authors present the results of study of corticotropine and cortizol secretion under the effect of stress caused by insulin hypoglycemia, of sensitivity of the adrenal glands to the administration of exogenous synthetic corticotropine, and of the 24-hour rhythm of the corticotropine and cortizol secretion in 26 healthy persons and in 57 patients suffering from Itsenko-Cushing's disease, including 25 after a course of treatment with chloditan, an inhibitor of the adrenal cortex function. Blood corticotropine content was determined by the radioimmunological method, and of cortizol--by competitive binding. There was revealed no significant increase of corticotropine and cortizol secretion in response to insulin hypoglycemia in Itsenko-Cushing's disease, this pointing to disturbance of the hypothalamo-hypophysio-adrenal system at the hypothalamic level. No qualitative differences were found in response of the adrenal cortex to corticotropine, this indicating the absence of changes of its sensitivity to this hormone. The 24-hour rhythm of corticotropine and cortizol secretion in this disease is inverted. At the immediate periods after chloditan treatment no normalization of the response of the adrenal cortex to insulin hypoglycemia, and of the 24-hour rhythm of corticotropine and cortizol secretion, and also of the changes in the adrenal cortex sensitivity to corticotropine was seen."}
{"id": "PMID:204920", "title": "[Stromal thecomatosis of the ovaries associated with the syndrome of mixed ovarian dysgenesis].", "content": "On the basis of analysis of a case of a combination of mixed dysgenesia of the ovaries with stromal thecomatosis and the clinical picture of the virile syndrome a conclusion was drawn that a) hypertestosteronemia was in such cases connected with the presence in the dysgenetic ovary and the connective tissue band of epitheliod cells forming the foci of stromal thecomatosis, and b) that the appearance of stromal thecomatosis failed to depend on the presence of the follicular apparatus; apparently cells of the interstitial tissue of the cortical layer of the ovaries serve as its source.", "contents": "[Stromal thecomatosis of the ovaries associated with the syndrome of mixed ovarian dysgenesis]. On the basis of analysis of a case of a combination of mixed dysgenesia of the ovaries with stromal thecomatosis and the clinical picture of the virile syndrome a conclusion was drawn that a) hypertestosteronemia was in such cases connected with the presence in the dysgenetic ovary and the connective tissue band of epitheliod cells forming the foci of stromal thecomatosis, and b) that the appearance of stromal thecomatosis failed to depend on the presence of the follicular apparatus; apparently cells of the interstitial tissue of the cortical layer of the ovaries serve as its source."}
{"id": "PMID:204921", "title": "[Disorders of lipid content of blood in diabetes mellitus].", "content": "The authors present the results of prospective study of the blood serum lipids (total cholesterol, triglycerides, lipoproteid fractions) in 132 patients with diabetes mellitus aged from 35 to 60 years and in 47 healthy persons of the same age (control group). The majority of the patients examined (60.6%) showed hyperlipidemia; types II and IV were most frequent. An increase in the content of the probeta-lipoproteid fraction and hypertriglyceridemia were mostly encountered in patients with macroangiopathies, particularly in the presence of adiposity. There was revealed no significant relationship between the frequency of hyperlipidemia and the severity of diabetes mellitus. However, the most distinct lipid disturbances were found in the patients with the disease of moderate severity. This was apparently connected with the prevalence in this group of persons with an excessive weight. As revealed, the incidence of hyperlipidemia rose on account of increased level of both total cholesterol and of triglycerides (with a tendency to their greater content in women).", "contents": "[Disorders of lipid content of blood in diabetes mellitus]. The authors present the results of prospective study of the blood serum lipids (total cholesterol, triglycerides, lipoproteid fractions) in 132 patients with diabetes mellitus aged from 35 to 60 years and in 47 healthy persons of the same age (control group). The majority of the patients examined (60.6%) showed hyperlipidemia; types II and IV were most frequent. An increase in the content of the probeta-lipoproteid fraction and hypertriglyceridemia were mostly encountered in patients with macroangiopathies, particularly in the presence of adiposity. There was revealed no significant relationship between the frequency of hyperlipidemia and the severity of diabetes mellitus. However, the most distinct lipid disturbances were found in the patients with the disease of moderate severity. This was apparently connected with the prevalence in this group of persons with an excessive weight. As revealed, the incidence of hyperlipidemia rose on account of increased level of both total cholesterol and of triglycerides (with a tendency to their greater content in women)."}
{"id": "PMID:204922", "title": "[Activity of glutathione reductase in the adrenal glands and the liver of dogs after administration O,P-DDD, perthane and ACTH].", "content": "A study was made of the inhibitors of the adrenal gland function and ACTH on the activity of NADP-specific glutathionreductase in the adrenal glands and the liver of dogs. After a 10-day feeding to dogs of o,p'-dichlordiphenyldichlorethane (o,p'-DDD) and p,p'-diethyldiphenyl dichlorethane (p,p'-pertane) in a dose of 50 mg/kg there was observed a marked activation of glutathion reductase in the adrenal glands. Elevation of the activity of the enzyme was revealed as soon as 24 hours after the administration of o,p'-DDD. The inhibitors under study failed to influence the activity of the enzyme in the liver of dogs, this indicating a specific action of o,p'-DDD and pertane on the adrenal gland cortex. Stimulation of glucocorticoid biosynthesis under the effect of ACTH administered once in a dose of 25 Units/kg was not accompanied by the changes in the activity of glutathione reductase in the adrenal glands and the liver of dogs. Prolonged ACTH administration (4 Units/kg) caused a significant reduction of the enzyme activity calculated as per 1 mg of protein in the adrenal gland homogenate.", "contents": "[Activity of glutathione reductase in the adrenal glands and the liver of dogs after administration O,P-DDD, perthane and ACTH]. A study was made of the inhibitors of the adrenal gland function and ACTH on the activity of NADP-specific glutathionreductase in the adrenal glands and the liver of dogs. After a 10-day feeding to dogs of o,p'-dichlordiphenyldichlorethane (o,p'-DDD) and p,p'-diethyldiphenyl dichlorethane (p,p'-pertane) in a dose of 50 mg/kg there was observed a marked activation of glutathion reductase in the adrenal glands. Elevation of the activity of the enzyme was revealed as soon as 24 hours after the administration of o,p'-DDD. The inhibitors under study failed to influence the activity of the enzyme in the liver of dogs, this indicating a specific action of o,p'-DDD and pertane on the adrenal gland cortex. Stimulation of glucocorticoid biosynthesis under the effect of ACTH administered once in a dose of 25 Units/kg was not accompanied by the changes in the activity of glutathione reductase in the adrenal glands and the liver of dogs. Prolonged ACTH administration (4 Units/kg) caused a significant reduction of the enzyme activity calculated as per 1 mg of protein in the adrenal gland homogenate."}
{"id": "PMID:204926", "title": "Blockade of neuromuscular transmission by enzymatically active and inactive beta-bungarotoxin.", "content": "beta-Bungarotoxins have been shown to be presynaptic blockers of neuromuscular transmission. This paper reports experiments using the most positively charged beta-bungarotoxin that elutes from a CM-Sephadex C-25 column. The toxin is shown to be a single polypeptide with a molecular weight of approximately 11,000 and has phospholipase A2 activity. The application of the enzymatically active toxin to the frog sciatic nerve-sartorius muscle preparation results in an initial decrease in the average endplate potential amplitude followed by a temporary rebound in endplate potential amplitude, and finally a complete inhibition of endplate potentials. Similarly, minature endplate potential frequency is initially reduced upon toxin application but then increases dramatically. After the phospholipase A2  of the toxin is inactivated, treatment with the toxin results in only the initial decrease in transmitter release. There results suggest that this beta-bungarotoxin acts in two functionally separate steps: (i) by binding to a specific presynaptic site possibly associated with calcium entry, and (ii) by perturbing the presynaptic membrane by its enzyme action, which results in an increase and then a failure in transmitter release.", "contents": "Blockade of neuromuscular transmission by enzymatically active and inactive beta-bungarotoxin. beta-Bungarotoxins have been shown to be presynaptic blockers of neuromuscular transmission. This paper reports experiments using the most positively charged beta-bungarotoxin that elutes from a CM-Sephadex C-25 column. The toxin is shown to be a single polypeptide with a molecular weight of approximately 11,000 and has phospholipase A2 activity. The application of the enzymatically active toxin to the frog sciatic nerve-sartorius muscle preparation results in an initial decrease in the average endplate potential amplitude followed by a temporary rebound in endplate potential amplitude, and finally a complete inhibition of endplate potentials. Similarly, minature endplate potential frequency is initially reduced upon toxin application but then increases dramatically. After the phospholipase A2  of the toxin is inactivated, treatment with the toxin results in only the initial decrease in transmitter release. There results suggest that this beta-bungarotoxin acts in two functionally separate steps: (i) by binding to a specific presynaptic site possibly associated with calcium entry, and (ii) by perturbing the presynaptic membrane by its enzyme action, which results in an increase and then a failure in transmitter release."}
{"id": "PMID:204927", "title": "An RNA transcribed from DNA at the origin of phage fd single strand to replicative form conversion.", "content": "Phage fd DNA complexed with DNA binding protein I was used by Escherichia coli RNA polymerase (nucleoside triphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) to synthesize an RNA at the origin of single strand to double strand replication. The isolated ori-RNA gave a simple fingerprint after nucleolytic digestion and has a length of about 30 nucleotides. The characterization of the oligonucleotides from the nuclease digest and the extension of the ori-RNA with DNA polymerase I and subsequent restriction of the DNA gave its exact localization in the fd genome, and its total sequence was deduced from the known DNA sequence in this region.", "contents": "An RNA transcribed from DNA at the origin of phage fd single strand to replicative form conversion. Phage fd DNA complexed with DNA binding protein I was used by Escherichia coli RNA polymerase (nucleoside triphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) to synthesize an RNA at the origin of single strand to double strand replication. The isolated ori-RNA gave a simple fingerprint after nucleolytic digestion and has a length of about 30 nucleotides. The characterization of the oligonucleotides from the nuclease digest and the extension of the ori-RNA with DNA polymerase I and subsequent restriction of the DNA gave its exact localization in the fd genome, and its total sequence was deduced from the known DNA sequence in this region."}
{"id": "PMID:204928", "title": "Characterization of pro-opiocortin, a precursor to opioid peptides and corticotropin.", "content": "The high molecular weight (approximately 30,000) precursor to opioid activity (pro-opiocortin) previously detected in extracts of rat pituitary was digested with trypsin and the resulting peptide mixture was resolved by high-performance reverse-phase chromatography. A peak of opioid activity was eluted at the position of the nonapeptide beta-LPH (61-69), which was also the same fragment obtained by trypsin digestion of betas-lipotropin or beta-endorphin. This identified the protein as a precursor to the endorphins and Met-enkephalin. No activity was detected in the position corresponding to the Leu5 analog of betas-LPH (61-69), thus ruling out the possibility of a beta-lipotropin-like precursor to Leu-enkephalin in pituitary extracts. Pro-opiocortin and beta-lipotropin are present in rat pituitary extracts in comparable amounts, approximately 10 pmol/mg of tissue.", "contents": "Characterization of pro-opiocortin, a precursor to opioid peptides and corticotropin. The high molecular weight (approximately 30,000) precursor to opioid activity (pro-opiocortin) previously detected in extracts of rat pituitary was digested with trypsin and the resulting peptide mixture was resolved by high-performance reverse-phase chromatography. A peak of opioid activity was eluted at the position of the nonapeptide beta-LPH (61-69), which was also the same fragment obtained by trypsin digestion of betas-lipotropin or beta-endorphin. This identified the protein as a precursor to the endorphins and Met-enkephalin. No activity was detected in the position corresponding to the Leu5 analog of betas-LPH (61-69), thus ruling out the possibility of a beta-lipotropin-like precursor to Leu-enkephalin in pituitary extracts. Pro-opiocortin and beta-lipotropin are present in rat pituitary extracts in comparable amounts, approximately 10 pmol/mg of tissue."}
{"id": "PMID:204929", "title": "In vitro synthesis of vesicular stomatitis virus membrane glycoprotein and insertion into membranes.", "content": "Translation in vitro of the mRNA coding for the vesicular stomatitis virus membrane glycoprotein G in a membrane-free ribosomal extract from HeLa cells allowed the synthesis of only the unglycosylated protein G1 (molecular weight, 63,000). Addition of stripped crude microsomal membranes from HeLa cells resulted in the conversion of G1 to the glycosylated protein G2 (molecular weight, 67,000). The G2 protein synthesized by the reconstructed microsomal membrane/ribosome system was found to be segregated inside the microsomal membrane vesicles and was thus protected from the proteolytic action of trypsin and chymotrypsin. Stripped membranes were required at an early stage of protein synthesis for the synthesized protein to be inserted into the membrane vesicles and to be glycosilated. The segregated protein G2, however, was not completely protected from proteolytic digestion, showing that a portion of the polypeptide chain of about 3000 daltons was present on the cytoplasmic side of the membrane vesicle. Our data thus suggest that, unlike the secretory proteins, the membrane glycoproteins are not completely discharged across the microsomal membranes.", "contents": "In vitro synthesis of vesicular stomatitis virus membrane glycoprotein and insertion into membranes. Translation in vitro of the mRNA coding for the vesicular stomatitis virus membrane glycoprotein G in a membrane-free ribosomal extract from HeLa cells allowed the synthesis of only the unglycosylated protein G1 (molecular weight, 63,000). Addition of stripped crude microsomal membranes from HeLa cells resulted in the conversion of G1 to the glycosylated protein G2 (molecular weight, 67,000). The G2 protein synthesized by the reconstructed microsomal membrane/ribosome system was found to be segregated inside the microsomal membrane vesicles and was thus protected from the proteolytic action of trypsin and chymotrypsin. Stripped membranes were required at an early stage of protein synthesis for the synthesized protein to be inserted into the membrane vesicles and to be glycosilated. The segregated protein G2, however, was not completely protected from proteolytic digestion, showing that a portion of the polypeptide chain of about 3000 daltons was present on the cytoplasmic side of the membrane vesicle. Our data thus suggest that, unlike the secretory proteins, the membrane glycoproteins are not completely discharged across the microsomal membranes."}
{"id": "PMID:204930", "title": "Triphosphate residues at the 5' ends of rRNA precursor and 5S RNA from Dictyostelium discoideum.", "content": "We present here direct evidence for the preservation of a transcriptional initiation sequence in a eukaryotic rRNA precursor: the 5'-end group for precursor to 17S rRNA (p17S RNA) from Dictyostelium discoideum is identified as the triphosphate residue pppA-. We also show that mature 5S RNA form Dictyostelium bears a different triphosphate residue, pppG-. In contrast, we find no evidence for more than one phosphate at the 5' end of the 25S rRNA precursor (p25S RNA). These observations indicate that synthesis of the large ribosomal RNAs of Dictyostelium begins with the 5'-terminal sequence of the p17S RNA, and that 5S RNA transcription must be initiated independently, despite the close association of the 5S and rRNA coding segments.", "contents": "Triphosphate residues at the 5' ends of rRNA precursor and 5S RNA from Dictyostelium discoideum. We present here direct evidence for the preservation of a transcriptional initiation sequence in a eukaryotic rRNA precursor: the 5'-end group for precursor to 17S rRNA (p17S RNA) from Dictyostelium discoideum is identified as the triphosphate residue pppA-. We also show that mature 5S RNA form Dictyostelium bears a different triphosphate residue, pppG-. In contrast, we find no evidence for more than one phosphate at the 5' end of the 25S rRNA precursor (p25S RNA). These observations indicate that synthesis of the large ribosomal RNAs of Dictyostelium begins with the 5'-terminal sequence of the p17S RNA, and that 5S RNA transcription must be initiated independently, despite the close association of the 5S and rRNA coding segments."}
{"id": "PMID:204931", "title": "Direct fluorescent assay of urokinase and plasminogen activators of normal and malignant cells: kinetics and inhibitor profiles.", "content": "A direct rate assay for plasminogen activator has been developed using a synthetic fluorogenic peptide substrate, 7-(N-Cbz-glycylglycylargininamido)-4-methylcoumarin trifluoroacetate. The assay correlates well with the standard 125I-labeled fibrin plate assay using highly purified urokinase, culture fluids from WI-38, Chinese hamster vary or HeLa cells, or Rous sarcoma virus-transformed chick fibroblasts as the source of plasminogen activator. The assay is sensitive, rapid, and linear throughout a wide range of enzyme concentrations. With this substrate it is possible to determine inhibitor profiles for the various plasminogen activators, independently of the interfering potential of plasmin. All of the enzymes tested are inhibited by leupeptin and antipain but not by the related aldehydes, elastatinal and chymostatin. The macromolecular inhibitors soybean trypsin inhibitor and trasylol have little or no effect on the plasminogen activators tested. This substrate should be useful for the study of the effect of various agents on functional changes in cells secreting this enzyme and also should allow kinetic measurements of potential inhibitors.", "contents": "Direct fluorescent assay of urokinase and plasminogen activators of normal and malignant cells: kinetics and inhibitor profiles. A direct rate assay for plasminogen activator has been developed using a synthetic fluorogenic peptide substrate, 7-(N-Cbz-glycylglycylargininamido)-4-methylcoumarin trifluoroacetate. The assay correlates well with the standard 125I-labeled fibrin plate assay using highly purified urokinase, culture fluids from WI-38, Chinese hamster vary or HeLa cells, or Rous sarcoma virus-transformed chick fibroblasts as the source of plasminogen activator. The assay is sensitive, rapid, and linear throughout a wide range of enzyme concentrations. With this substrate it is possible to determine inhibitor profiles for the various plasminogen activators, independently of the interfering potential of plasmin. All of the enzymes tested are inhibited by leupeptin and antipain but not by the related aldehydes, elastatinal and chymostatin. The macromolecular inhibitors soybean trypsin inhibitor and trasylol have little or no effect on the plasminogen activators tested. This substrate should be useful for the study of the effect of various agents on functional changes in cells secreting this enzyme and also should allow kinetic measurements of potential inhibitors."}
{"id": "PMID:204932", "title": "Oligosaccharide chains are trimmed during synthesis of the envelope glycoprotein of vesicular stomatitis virus.", "content": "The biosynthesis and maturation of the oligosaccharide moieties of the envelope glycoprotein of vesicular stomatitis virus were investigated in virus-infected HeLa and BHK21 cells after pulse labeling with [2-3H]mannose. Two major forms of the virus glycoprotein were detected by polyacrylamide gel electrophoresis, which appear to correspond to the viral glycoprotein with either \"precursor\" or \"mature\" oligosaccharide chains. The precursor chains in both HeLa and BHK21 cells infected with vesicular stomatitis virus obtained after a 30-min pulse were large oligomannose structures containing approximately 7--9 mannose residues as estimated by gel filtration analysis. The size of the oligomannose structures initially transferred to the protein may have been even larger. Mature, virus-size oligosaccharide chains, which could be detected after a 20- to 30-min delay, contained only three mannose residues and, in addition, contained branch structures terminating in sialic acid. A precursor--product relationship of these two forms of oligosaccharide chains was demonstrated by pulse--chase labeling of virus-infected HeLa cells. These studies indicated that the large oligomannosyl core structures initially added to the glycoprotein were being \"trimmed\" by the removal of mannose residues prior to (and/or during) the addition of the branch chains terminating in sialic acid.", "contents": "Oligosaccharide chains are trimmed during synthesis of the envelope glycoprotein of vesicular stomatitis virus. The biosynthesis and maturation of the oligosaccharide moieties of the envelope glycoprotein of vesicular stomatitis virus were investigated in virus-infected HeLa and BHK21 cells after pulse labeling with [2-3H]mannose. Two major forms of the virus glycoprotein were detected by polyacrylamide gel electrophoresis, which appear to correspond to the viral glycoprotein with either \"precursor\" or \"mature\" oligosaccharide chains. The precursor chains in both HeLa and BHK21 cells infected with vesicular stomatitis virus obtained after a 30-min pulse were large oligomannose structures containing approximately 7--9 mannose residues as estimated by gel filtration analysis. The size of the oligomannose structures initially transferred to the protein may have been even larger. Mature, virus-size oligosaccharide chains, which could be detected after a 20- to 30-min delay, contained only three mannose residues and, in addition, contained branch structures terminating in sialic acid. A precursor--product relationship of these two forms of oligosaccharide chains was demonstrated by pulse--chase labeling of virus-infected HeLa cells. These studies indicated that the large oligomannosyl core structures initially added to the glycoprotein were being \"trimmed\" by the removal of mannose residues prior to (and/or during) the addition of the branch chains terminating in sialic acid."}
{"id": "PMID:204933", "title": "Alteration of the physicochemical properties of triphosphoinositide by nicotinic ligands.", "content": "The concentrations of nicotinic drugs required to effect a 50% transfer of triphosphol[3H]isositide from an aqueous phase to a nonaqueous phase closely approximated their concentrations for both in vivo neuromuscular blocking activity and binding to purified nicotinic receptors, and correlated well (correlation coefficient = 0.95)) with their biological activities measured by other workers in an Electrophorus electroplax preparation. The triphospho[3H]inositide transfer induced by nicotinic ligands was dependent on the lipid concentration and was potentiated by Ca2+. The affinity constants of 45Ca2+ for triphosphoinositide were similar to those for the purified nicotinic receptor. These and other findings suggest the possibility that triphosphoinositide (phosphatidylinositol bisphosphate) is a binding site of the nicotinic receptor.", "contents": "Alteration of the physicochemical properties of triphosphoinositide by nicotinic ligands. The concentrations of nicotinic drugs required to effect a 50% transfer of triphosphol[3H]isositide from an aqueous phase to a nonaqueous phase closely approximated their concentrations for both in vivo neuromuscular blocking activity and binding to purified nicotinic receptors, and correlated well (correlation coefficient = 0.95)) with their biological activities measured by other workers in an Electrophorus electroplax preparation. The triphospho[3H]inositide transfer induced by nicotinic ligands was dependent on the lipid concentration and was potentiated by Ca2+. The affinity constants of 45Ca2+ for triphosphoinositide were similar to those for the purified nicotinic receptor. These and other findings suggest the possibility that triphosphoinositide (phosphatidylinositol bisphosphate) is a binding site of the nicotinic receptor."}
{"id": "PMID:204934", "title": "Structure of a poly (adenosine diphosphoribose) monomer: 2'-(5\"-hosphoribosyl)-5'-adenosine monophosphate.", "content": "A preparation of poly(adenosine diphosphoribose) synthase obtained from pigeon liver nuclei has been used to make poly(adenosine diphosphoribose) with an average chain length of 20. Digestion of the purified poly(adenosine diphosphoribose) with snake venom phosphodiesterase (oligonucleate 5'-nucleotidohydrolase; EC 3.1.4.1) gave the monomer, 2'-(5\"-phosphoribosyl)-5-AMP. After purification of the monomer on a Dowex-1 column, further digestion with alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum); EC 3.1.3.1] yielded the dephosphorylated product, 2'-ribosyl adenosine. Nuclear magnetic resonance spectra at 360 MHz of the 2'-ribosyl adenosine were obtained in [2H6]dimethylsulfoxide, which allows direct observation of the hydroxyl protons. These spectra show the absence of the adenosine 2'-hydroxyl proton, thus confirming the 2' position as the site of attachment of the ribose to the adenosine moiety. Comparison of the coupling constants and the chemical shifts of the ribose hydroxyl protons of 2'-ribosyl adenosine with the model compounds alpha- and beta-methylribofuranoside establishes an alpha (1\" leads to 2') glycosidic linkage in the monomer. No evidence was found for heterogeneity in either the site of attachment or configuration of the linkage in the 2'-(5\"-phosphoribosyl)-5'-AMP.", "contents": "Structure of a poly (adenosine diphosphoribose) monomer: 2'-(5\"-hosphoribosyl)-5'-adenosine monophosphate. A preparation of poly(adenosine diphosphoribose) synthase obtained from pigeon liver nuclei has been used to make poly(adenosine diphosphoribose) with an average chain length of 20. Digestion of the purified poly(adenosine diphosphoribose) with snake venom phosphodiesterase (oligonucleate 5'-nucleotidohydrolase; EC 3.1.4.1) gave the monomer, 2'-(5\"-phosphoribosyl)-5-AMP. After purification of the monomer on a Dowex-1 column, further digestion with alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum); EC 3.1.3.1] yielded the dephosphorylated product, 2'-ribosyl adenosine. Nuclear magnetic resonance spectra at 360 MHz of the 2'-ribosyl adenosine were obtained in [2H6]dimethylsulfoxide, which allows direct observation of the hydroxyl protons. These spectra show the absence of the adenosine 2'-hydroxyl proton, thus confirming the 2' position as the site of attachment of the ribose to the adenosine moiety. Comparison of the coupling constants and the chemical shifts of the ribose hydroxyl protons of 2'-ribosyl adenosine with the model compounds alpha- and beta-methylribofuranoside establishes an alpha (1\" leads to 2') glycosidic linkage in the monomer. No evidence was found for heterogeneity in either the site of attachment or configuration of the linkage in the 2'-(5\"-phosphoribosyl)-5'-AMP."}
{"id": "PMID:204935", "title": "Ionophore A-23187- and thrombin-induced platelet aggregation: independence from cycloxygenase products.", "content": "Stimulation of platelets labeled with [14C]-arachidonate by ionophore A23187 or thrombin produces rapid degradation of specific membrane phospholipids. This is also reflected by the release of [14C]archidonate, which is immediately transformed into products of the cycloxygenase and lipoxygenase enzyme systems, and by increased labeling of phosphatidic acid. Arachidonate metabolism can be effectively prevented by preincubation with indomethacin and eicosatetraynoic acid, but platelet aggregation induced by ionophore A23187 or trombin is not blocked under these conditions. Nevertheless, in the virtually total absence of metabolism of arachidonate, platelet aggregation still occurs concomitantly with phospholipid breakdown and with increased labeling of phosphatidic acid. Increased levels of cyclic AMP block both phospholipase activation and aggregation induced by ionophore A23187 and trombin. These data suggest that some early consequence of phospholipase activation, independent of a metabolic product of arachidonate but possibly related to the production of phosphatidic acid, may play a central, causative role in mediating platelet aggregation.", "contents": "Ionophore A-23187- and thrombin-induced platelet aggregation: independence from cycloxygenase products. Stimulation of platelets labeled with [14C]-arachidonate by ionophore A23187 or thrombin produces rapid degradation of specific membrane phospholipids. This is also reflected by the release of [14C]archidonate, which is immediately transformed into products of the cycloxygenase and lipoxygenase enzyme systems, and by increased labeling of phosphatidic acid. Arachidonate metabolism can be effectively prevented by preincubation with indomethacin and eicosatetraynoic acid, but platelet aggregation induced by ionophore A23187 or trombin is not blocked under these conditions. Nevertheless, in the virtually total absence of metabolism of arachidonate, platelet aggregation still occurs concomitantly with phospholipid breakdown and with increased labeling of phosphatidic acid. Increased levels of cyclic AMP block both phospholipase activation and aggregation induced by ionophore A23187 and trombin. These data suggest that some early consequence of phospholipase activation, independent of a metabolic product of arachidonate but possibly related to the production of phosphatidic acid, may play a central, causative role in mediating platelet aggregation."}
{"id": "PMID:204936", "title": "Erythrocyte membrane abnormalities in Duchenne muscular dystrophy monitored by saturation transfer electron paramagnetic resonance spectroscopy.", "content": "Saturation transfer electron paramagnetic resonance and the spin label 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl were used to study erythrocytes from patients with Duchenne muscular dystrophy or Becker syndrome and from age-matched normal boys. There were significant differences in the spectral intensities of erythrocytes from Duchenne patients when compared to controls. Spectral intensities increased with time in the former; no such change was observed in the latter. Saturation transfer electron paramagnetic resonance spectra of erythrocytes from patients with Becker syndrome were significantly different from those from Duchenne patients but were not significantly different from normals. These observations suggest the possible usefulness of these techniques in the differential diagnosis of Duchenne muscular dystrophy. Spin label concentration spectral studies suggest that the observed spectral differences between Duchenne patients and controls were due to differential spin exchange phenomena.", "contents": "Erythrocyte membrane abnormalities in Duchenne muscular dystrophy monitored by saturation transfer electron paramagnetic resonance spectroscopy. Saturation transfer electron paramagnetic resonance and the spin label 2-(3-carboxypropyl)-4,4-dimethyl-2-tridecyl-3-oxazolidinyloxyl were used to study erythrocytes from patients with Duchenne muscular dystrophy or Becker syndrome and from age-matched normal boys. There were significant differences in the spectral intensities of erythrocytes from Duchenne patients when compared to controls. Spectral intensities increased with time in the former; no such change was observed in the latter. Saturation transfer electron paramagnetic resonance spectra of erythrocytes from patients with Becker syndrome were significantly different from those from Duchenne patients but were not significantly different from normals. These observations suggest the possible usefulness of these techniques in the differential diagnosis of Duchenne muscular dystrophy. Spin label concentration spectral studies suggest that the observed spectral differences between Duchenne patients and controls were due to differential spin exchange phenomena."}
{"id": "PMID:204937", "title": "Cyclic AMP-dependent protein kinase mediates a cyclic AMP-stimulated decrease in ornithine and S-adenosylmethionine decarboxylase activities.", "content": "Incubation of S49 lymphoma cells with N6,O2'-dibutyryl cyclic AMP (Bt2cAMP) decreases the activities of ornithine decarboxylase (L-ornithine carboxy-lyase; EC 4.1.1.17) and S-adenosylmethionine decarboxylase (S-adenosyl-L-methionine carboxy-lyase; EC 4.1.1.50), the two principal enzymes in the pathway of polyamine synthesis. This decrease is dose-dependent, commences after a 3-hr delay, virtually abolishes the assayable activities of the two enzymes, and is not associated with a soluble inhibitor of the enzyme activities. Studies in mutant S49 clones that have altered protein kinase indicate that cAMP-dependent protein kinase mediates the decreases in enzyme activities. The dose-response pattern for the cAMP-stimulated decrease in enzyme activities parallels the pattern for the cAMP-stimulated, cell cycle-specific (G1) growth arrest of S49 cells. The activity of ornithine decarboxylase decreases faster than Bt2cAMP arrests wild-type S49 cells and, similarly, release of cells from the cAMP-stimulated arrest in G1 increases the activity of ornithine decarboxylase faster than cells exit from G1. These findings contrast with reports that cAMP induces ornithine decarboxylase in other cell types and further suggest that passage of cells through cell cycle is required for maintaining the activities of ornithine and S-adenosylmethionine decarboxylases.", "contents": "Cyclic AMP-dependent protein kinase mediates a cyclic AMP-stimulated decrease in ornithine and S-adenosylmethionine decarboxylase activities. Incubation of S49 lymphoma cells with N6,O2'-dibutyryl cyclic AMP (Bt2cAMP) decreases the activities of ornithine decarboxylase (L-ornithine carboxy-lyase; EC 4.1.1.17) and S-adenosylmethionine decarboxylase (S-adenosyl-L-methionine carboxy-lyase; EC 4.1.1.50), the two principal enzymes in the pathway of polyamine synthesis. This decrease is dose-dependent, commences after a 3-hr delay, virtually abolishes the assayable activities of the two enzymes, and is not associated with a soluble inhibitor of the enzyme activities. Studies in mutant S49 clones that have altered protein kinase indicate that cAMP-dependent protein kinase mediates the decreases in enzyme activities. The dose-response pattern for the cAMP-stimulated decrease in enzyme activities parallels the pattern for the cAMP-stimulated, cell cycle-specific (G1) growth arrest of S49 cells. The activity of ornithine decarboxylase decreases faster than Bt2cAMP arrests wild-type S49 cells and, similarly, release of cells from the cAMP-stimulated arrest in G1 increases the activity of ornithine decarboxylase faster than cells exit from G1. These findings contrast with reports that cAMP induces ornithine decarboxylase in other cell types and further suggest that passage of cells through cell cycle is required for maintaining the activities of ornithine and S-adenosylmethionine decarboxylases."}
{"id": "PMID:204938", "title": "Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides.", "content": "The chemotactice response of human dermal fibroblasts of type I, II, and III human collagens and collagen-derived peptides was quantitated by an in vitro assay. All three native human collagens and constituent alpha chains can serve as chemoattractants for fibroblasts in vitro. When type I, II, and III collagens were digested by bacterial collagenase, the resulting peptides were also chemotactic. In addition, synthetic di- and tripeptides containing hydroxyproline were also chemotactic for fibroblasts. Since collagen is degraded and remodeled at sites of tissue injury and inflammation, these findings suggest that collagen and collagen-degradation peptides might function as chemotactic stimuli for fibroblasts in vivo and attract these cells to effect repair of damaged tissue.", "contents": "Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides. The chemotactice response of human dermal fibroblasts of type I, II, and III human collagens and collagen-derived peptides was quantitated by an in vitro assay. All three native human collagens and constituent alpha chains can serve as chemoattractants for fibroblasts in vitro. When type I, II, and III collagens were digested by bacterial collagenase, the resulting peptides were also chemotactic. In addition, synthetic di- and tripeptides containing hydroxyproline were also chemotactic for fibroblasts. Since collagen is degraded and remodeled at sites of tissue injury and inflammation, these findings suggest that collagen and collagen-degradation peptides might function as chemotactic stimuli for fibroblasts in vivo and attract these cells to effect repair of damaged tissue."}
{"id": "PMID:204939", "title": "Cotransfer of thymidine kinase and galactokinase genes by chromosome-mediated gene transfer.", "content": "The Chinese hamster genes for thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) and galactokinase (ATP:D-galactose 1-phosphotransferase, EC 2.7.1.6) have been cotransferred to mouse cells by chromosome-mediated gene transfer. Hamster metaphase chromosomes were incubated with mouse B82 cells and 22 independent colonies were isolated in a selective medium. All of the 12 colonies analyzed expressed the donor form of thymidine kinase; the hamster form of galactokinase was also expressed in 2 of these colonies, indicating cotransfer with a frequency of about 20%. There was coordinate loss of both transferred genes from each colony when selection was applied for the loss of thymidine kinase alone. Comparison of the regional localization of these two linked genes with the frequency of cotransfer suggests that the transgenome is probably not larger than about 0.25% of the donor genome.", "contents": "Cotransfer of thymidine kinase and galactokinase genes by chromosome-mediated gene transfer. The Chinese hamster genes for thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.75) and galactokinase (ATP:D-galactose 1-phosphotransferase, EC 2.7.1.6) have been cotransferred to mouse cells by chromosome-mediated gene transfer. Hamster metaphase chromosomes were incubated with mouse B82 cells and 22 independent colonies were isolated in a selective medium. All of the 12 colonies analyzed expressed the donor form of thymidine kinase; the hamster form of galactokinase was also expressed in 2 of these colonies, indicating cotransfer with a frequency of about 20%. There was coordinate loss of both transferred genes from each colony when selection was applied for the loss of thymidine kinase alone. Comparison of the regional localization of these two linked genes with the frequency of cotransfer suggests that the transgenome is probably not larger than about 0.25% of the donor genome."}
{"id": "PMID:204940", "title": "Antibody response of mice to chemically induced tumors.", "content": "BALB/c mice immunized with syngeneic methylcholanthrene-induced fibrosarcomas did not have antibodies against the unique tumor-specific transplantation antigens, even though they were capable of rejecting a lethal dose of tumor cells. Endogenous murine leukemia virus antigens expressed by certain of the tumors did, however, elicit high titers of antibodies, accounting for serological crossreactions that occurred between those tumors.", "contents": "Antibody response of mice to chemically induced tumors. BALB/c mice immunized with syngeneic methylcholanthrene-induced fibrosarcomas did not have antibodies against the unique tumor-specific transplantation antigens, even though they were capable of rejecting a lethal dose of tumor cells. Endogenous murine leukemia virus antigens expressed by certain of the tumors did, however, elicit high titers of antibodies, accounting for serological crossreactions that occurred between those tumors."}
{"id": "PMID:204941", "title": "Vesicular stomatitis virus glycoprotein is necessary for H-2-restricted lysis of infected cells by cytotoxic T lymphocytes.", "content": "Vesicular stomatitis virus (VSV) elicited cytotoxic thymus-derived lymphocytes (CTLs) in mice of the BALB/c and three congenic strains (BALB.b, BALB.k, BALB.HTG). CTL lysis of VSV-infected fibroblasts from the four strains was restricted by the target cells' major histocompatibility complex (H-2). Target cells were also infected with two temperature-sensitive mutants of VSV, tsM and tsG in which, respectively, the viral matrix protein and glycoprotein are not expressed at 39 degrees (restrictive temperature) on the infected cell's surface membrane. At the restrictive temperature, cells infected with wild-type VSV or tsM were lysed by CTLs, but cells infected with tsG were not. The requirement for the glycoprotein on the target cell was also evident from the ability of antisera to the glycoprotein to block completely CTL lysis of VSV-infected cells.", "contents": "Vesicular stomatitis virus glycoprotein is necessary for H-2-restricted lysis of infected cells by cytotoxic T lymphocytes. Vesicular stomatitis virus (VSV) elicited cytotoxic thymus-derived lymphocytes (CTLs) in mice of the BALB/c and three congenic strains (BALB.b, BALB.k, BALB.HTG). CTL lysis of VSV-infected fibroblasts from the four strains was restricted by the target cells' major histocompatibility complex (H-2). Target cells were also infected with two temperature-sensitive mutants of VSV, tsM and tsG in which, respectively, the viral matrix protein and glycoprotein are not expressed at 39 degrees (restrictive temperature) on the infected cell's surface membrane. At the restrictive temperature, cells infected with wild-type VSV or tsM were lysed by CTLs, but cells infected with tsG were not. The requirement for the glycoprotein on the target cell was also evident from the ability of antisera to the glycoprotein to block completely CTL lysis of VSV-infected cells."}
{"id": "PMID:204942", "title": "Control of aldosterone secretion during sodium restriction: adrenal receptor regulation and increased adrenal sensitivity to angiotensin II.", "content": "The mechanism of increased adrenal sensitivity to angiotensin II during the aldosterone response to sodium restriction was investigated in the rat. Sodium restriction for 36 hr markedly increased the aldosterone-stimulating effect of low-dose (1 ng/min) infusion of angiotensin II and caused enhanced binding of (125)I-labeled angiotensin II to the zona glomerulosa in vivo. Conversely, in vivo binding of (125)I-labeled angiotensin II was significantly decreased after 36 hr of high-sodium intake. In isolated glomerulosa cells, the increased binding of angiotensin II after sodium restriction was shown to result from a significant increase in receptor affinity (+80%) and a smaller increase in receptor concentration (+25%). The corresponding aldosterone responses in dispersed cells showed an increase in sensitivity to angiotensin II, commensurate with the increased receptor affinity. More prolonged sodium restriction (4 days) caused a further increase in angiotensin receptor concentration (+70%) and maximal aldosterone response (+50%), whereas the binding affinity of adrenal receptors and the sensitivity of the in vitro aldosterone response had returned to normal. During sodium loading for 36 hr and 4 days, the converse effects on adrenal angiotensin II receptors and aldosterone production were observed. Also, in contrast to the consistent increase in angiotensin II receptors in the adrenal glands of sodium-restricted animals, the angiotensin II binding capacity of uterine smooth muscle was decreased by 40% after 7 days of sodium restriction.The rapid regulation of receptor affinity and concentration during changes in sodium intake provides a basis for the dynamic modulation of aldosterone responses by dietary sodium content. During sodium restriction, the sequential changes in receptor affinity and concentration account for the enhanced binding and steroidogenic actions of angiotensin II in vivo and in vitro. These receptor changes, and the converse effects of sodium loading, serve as a local regulatory mechanism in the physiological control of adrenal sensitivity and aldosterone secretion. The opposite finding in smooth muscle-that sodium restriction decreases the concentration of angiotensin II receptors-is consistent with the divergent effects of changing sodium balance upon vascular and adrenal responses to angiotensin II.", "contents": "Control of aldosterone secretion during sodium restriction: adrenal receptor regulation and increased adrenal sensitivity to angiotensin II. The mechanism of increased adrenal sensitivity to angiotensin II during the aldosterone response to sodium restriction was investigated in the rat. Sodium restriction for 36 hr markedly increased the aldosterone-stimulating effect of low-dose (1 ng/min) infusion of angiotensin II and caused enhanced binding of (125)I-labeled angiotensin II to the zona glomerulosa in vivo. Conversely, in vivo binding of (125)I-labeled angiotensin II was significantly decreased after 36 hr of high-sodium intake. In isolated glomerulosa cells, the increased binding of angiotensin II after sodium restriction was shown to result from a significant increase in receptor affinity (+80%) and a smaller increase in receptor concentration (+25%). The corresponding aldosterone responses in dispersed cells showed an increase in sensitivity to angiotensin II, commensurate with the increased receptor affinity. More prolonged sodium restriction (4 days) caused a further increase in angiotensin receptor concentration (+70%) and maximal aldosterone response (+50%), whereas the binding affinity of adrenal receptors and the sensitivity of the in vitro aldosterone response had returned to normal. During sodium loading for 36 hr and 4 days, the converse effects on adrenal angiotensin II receptors and aldosterone production were observed. Also, in contrast to the consistent increase in angiotensin II receptors in the adrenal glands of sodium-restricted animals, the angiotensin II binding capacity of uterine smooth muscle was decreased by 40% after 7 days of sodium restriction.The rapid regulation of receptor affinity and concentration during changes in sodium intake provides a basis for the dynamic modulation of aldosterone responses by dietary sodium content. During sodium restriction, the sequential changes in receptor affinity and concentration account for the enhanced binding and steroidogenic actions of angiotensin II in vivo and in vitro. These receptor changes, and the converse effects of sodium loading, serve as a local regulatory mechanism in the physiological control of adrenal sensitivity and aldosterone secretion. The opposite finding in smooth muscle-that sodium restriction decreases the concentration of angiotensin II receptors-is consistent with the divergent effects of changing sodium balance upon vascular and adrenal responses to angiotensin II."}
{"id": "PMID:204943", "title": "Extrahypophysial distribution of corticotropin as a function of brain size.", "content": "Determination by radioimmunoassay of corticotropin in the brains of rats, rabbits, dogs, monkeys, and human beings reveals that the dimensions within which the hormone is found is about the same for each of these species but that the anatomical regions in which the hormone is found depends on brain size. Corticotropin is widely distributed in the brain of rats but is found only in the hypothalamic region of the primate brain. The patterns of immunoreactivity observed after Sephadex gel filtration confirm that the molecular forms of corticotropin found in extrahypophysial regions are similar to those in the pituitary of each species. These findings suggest that the mammalian pituitary is the sole site of synthesis of the hormone. The observation of persistence of corticotropin in the brains of commerically hypophysectomized rats has been interpreted by others as suggesting diencephalic as well as pituitary origin for this peptide. However, our studies demonstrate that 8 weeks after hypophysectomy the rats we have received from commerical sources manifest stress-stimulated plasma corticotropin concentrations about 80% of that found in intact rats in spite of the fact that residual pituitary tissue was not found by visual inspection of the sella. Scrapings from the sella revealed a corticotropin content up to 5% that of the average rat pituitary.", "contents": "Extrahypophysial distribution of corticotropin as a function of brain size. Determination by radioimmunoassay of corticotropin in the brains of rats, rabbits, dogs, monkeys, and human beings reveals that the dimensions within which the hormone is found is about the same for each of these species but that the anatomical regions in which the hormone is found depends on brain size. Corticotropin is widely distributed in the brain of rats but is found only in the hypothalamic region of the primate brain. The patterns of immunoreactivity observed after Sephadex gel filtration confirm that the molecular forms of corticotropin found in extrahypophysial regions are similar to those in the pituitary of each species. These findings suggest that the mammalian pituitary is the sole site of synthesis of the hormone. The observation of persistence of corticotropin in the brains of commerically hypophysectomized rats has been interpreted by others as suggesting diencephalic as well as pituitary origin for this peptide. However, our studies demonstrate that 8 weeks after hypophysectomy the rats we have received from commerical sources manifest stress-stimulated plasma corticotropin concentrations about 80% of that found in intact rats in spite of the fact that residual pituitary tissue was not found by visual inspection of the sella. Scrapings from the sella revealed a corticotropin content up to 5% that of the average rat pituitary."}
{"id": "PMID:204944", "title": "Infection of mouse preimplantation embryos with simian virus 40 and polyoma virus.", "content": "Mouse two-cell embryos, morulae, and blastocysts were killed when infected in vitro with simian virus 40 (SV40) at high multiplicities of infection. Polyoma virus was not deleterious for preimplantation embryos, even at a very high multiplicity of infection; however, the outgrowths of polyoma-infected blastocysts disintegrated after several days of culture. Indirect immunofluorescence tests revealed the presence of SV40 T and V antigens and polyoma virus V antigen in the nuclei of trophoblastic cells. Virus-specific antigens were not found in the nuclei of cells forming inner cell masses of blastocysts or in inner cell mass-derived cells in blastocyst out-growths. The appearance of SV40 T and V antigens in the nuclei was inhibited by alphaamanitin, a RNA polymerase II inhibitor. The amount of infectious virus recovered from cultures of morulae or blastocysts on subsequent days after infection with SV40 initially declined but later increased. These points of evidence indicate that some cells of early mouse embryos are permissive for the expression of early and late functions of SV40 genome and that susceptibility to infection with polyoma virus and/or permissiveness for the expression of polyoma virus late functions develop gradually between the two-cell and blastocyst stages. Electron microscope observations showed the presence of specific complexes of membranes and virions in the cytoplasm of trophoblastic cells. Single viral particles could be found in the nuclei and also in mitochondria.", "contents": "Infection of mouse preimplantation embryos with simian virus 40 and polyoma virus. Mouse two-cell embryos, morulae, and blastocysts were killed when infected in vitro with simian virus 40 (SV40) at high multiplicities of infection. Polyoma virus was not deleterious for preimplantation embryos, even at a very high multiplicity of infection; however, the outgrowths of polyoma-infected blastocysts disintegrated after several days of culture. Indirect immunofluorescence tests revealed the presence of SV40 T and V antigens and polyoma virus V antigen in the nuclei of trophoblastic cells. Virus-specific antigens were not found in the nuclei of cells forming inner cell masses of blastocysts or in inner cell mass-derived cells in blastocyst out-growths. The appearance of SV40 T and V antigens in the nuclei was inhibited by alphaamanitin, a RNA polymerase II inhibitor. The amount of infectious virus recovered from cultures of morulae or blastocysts on subsequent days after infection with SV40 initially declined but later increased. These points of evidence indicate that some cells of early mouse embryos are permissive for the expression of early and late functions of SV40 genome and that susceptibility to infection with polyoma virus and/or permissiveness for the expression of polyoma virus late functions develop gradually between the two-cell and blastocyst stages. Electron microscope observations showed the presence of specific complexes of membranes and virions in the cytoplasm of trophoblastic cells. Single viral particles could be found in the nuclei and also in mitochondria."}
{"id": "PMID:204947", "title": "Oral absorption and selective tissue localization of 4'-(9-acridinylamino)-methanesulfon-m-anisidide.", "content": "The disposition of 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA), a new antitumor agent presently undergoing clinical evaluation, was studied in mice and rats following oral administration and compared to that observed following intravenous administration. The metabolic fate of  AMSA was the same with either intravenous or oral administration; however, the tissue distribution of AMSA differed significantly between the two routes of administration. Following absorption from the GI tract, AMSA was rapidly cleared from plasma by the liver and excreted in the bile as metabolites. Concentrations of AMSA in the liver were relatively high after oral administration and were sufficient to exert a cytotoxic effect on L1210 cells implanted at the site. The results indicate the use of AMSA orally to attain selective localization in the liver with decreased systemic exposure, which may prove useful against tumor metastases to the liver or primary hepatocellular carcinoma.", "contents": "Oral absorption and selective tissue localization of 4'-(9-acridinylamino)-methanesulfon-m-anisidide. The disposition of 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA), a new antitumor agent presently undergoing clinical evaluation, was studied in mice and rats following oral administration and compared to that observed following intravenous administration. The metabolic fate of  AMSA was the same with either intravenous or oral administration; however, the tissue distribution of AMSA differed significantly between the two routes of administration. Following absorption from the GI tract, AMSA was rapidly cleared from plasma by the liver and excreted in the bile as metabolites. Concentrations of AMSA in the liver were relatively high after oral administration and were sufficient to exert a cytotoxic effect on L1210 cells implanted at the site. The results indicate the use of AMSA orally to attain selective localization in the liver with decreased systemic exposure, which may prove useful against tumor metastases to the liver or primary hepatocellular carcinoma."}
{"id": "PMID:204948", "title": "Selective localization of 4'-(9-acridinylamino)-methanesulfon-m-anisidide in B 16 melanoma.", "content": "The acridine derivative 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA, NSC-141549), a new antitumor agent undergoing phase I clinical evaluation, is highly active against B16 melanoma in vivo. AMSA was found to be concentrated in B16 melanoma cells in vivo and remained at high concentrations for at least 72 h. Subcellular fractionation of B16 melanoma cells revealed the drug to be bound to melanin granules. The results suggest the possible use of AMSA in human melanoma and the design of other antimelanoma agents that would exploit the affinity of the acridine nucleus for melanin.", "contents": "Selective localization of 4'-(9-acridinylamino)-methanesulfon-m-anisidide in B 16 melanoma. The acridine derivative 4'-(9-acridinylamino)-methanesulfon-m-anisidide (AMSA, NSC-141549), a new antitumor agent undergoing phase I clinical evaluation, is highly active against B16 melanoma in vivo. AMSA was found to be concentrated in B16 melanoma cells in vivo and remained at high concentrations for at least 72 h. Subcellular fractionation of B16 melanoma cells revealed the drug to be bound to melanin granules. The results suggest the possible use of AMSA in human melanoma and the design of other antimelanoma agents that would exploit the affinity of the acridine nucleus for melanin."}
{"id": "PMID:204949", "title": "Application of EEG sleep for the differential diagnosis and treatment of affective disorders.", "content": "In the last decade all night EEG sleep research has attempted to delineate the sleep features most characteristics of depressive states occurring in adult life. We have reported that EEG sleep variables could be used to verify a diagnostic classification for affective syndromes. This EEG sleep generated schema significantly dichotimized each major clinical category using only two or three EEG sleep measures. REM latency and REM density were sufficient to separate out primary from secondary depressed patients. Sleep efficiency, REM sleep percent, and delta sleep percent discriminated between the psychotic and nonpsychotic subgroups in the primary depressive group. Furthermore, EEG sleep variables separated secondary depression with concurrent medical disease from secondary depression without medical disease using REM activity and intermittent nocturnal awakening as the requisite variables of discrimination. Other ongoing investigations have established that the REM intensity of the first REM period is increased in primary depression. The search for EEG sleep correlates of clinical response in depressed patients receiving tricyclic antidepressants has suggested that, the more rapid the suppression of REM sleep, the more likely that the patient will respond to tricyclic antidepressants. Finally, clinical response appears to be associated with a period of sustained elevation of REM latency.", "contents": "Application of EEG sleep for the differential diagnosis and treatment of affective disorders. In the last decade all night EEG sleep research has attempted to delineate the sleep features most characteristics of depressive states occurring in adult life. We have reported that EEG sleep variables could be used to verify a diagnostic classification for affective syndromes. This EEG sleep generated schema significantly dichotimized each major clinical category using only two or three EEG sleep measures. REM latency and REM density were sufficient to separate out primary from secondary depressed patients. Sleep efficiency, REM sleep percent, and delta sleep percent discriminated between the psychotic and nonpsychotic subgroups in the primary depressive group. Furthermore, EEG sleep variables separated secondary depression with concurrent medical disease from secondary depression without medical disease using REM activity and intermittent nocturnal awakening as the requisite variables of discrimination. Other ongoing investigations have established that the REM intensity of the first REM period is increased in primary depression. The search for EEG sleep correlates of clinical response in depressed patients receiving tricyclic antidepressants has suggested that, the more rapid the suppression of REM sleep, the more likely that the patient will respond to tricyclic antidepressants. Finally, clinical response appears to be associated with a period of sustained elevation of REM latency."}
{"id": "PMID:204950", "title": "Functional aspects of the norepinephrine receptor coupled adenylate cyclase system in the limbic forebrain and its modification by drugs which precipitate or alleviate depression: molecular approaches to an understanding of affective disorders.", "content": "The results provide evidence for a central postsynaptic regulatory mechanism involving the noradrenergic receptor coupled adenylate cyclase system. This particular system in the limbic forebrain displays properties of an adrenergic receptor with partial beta characteristics. Drugs which either can precipitate or alleviate depression in man cause time dependent opposite changes in the reactivity of this receptor system. It is tempting to speculate that depression-prone patients may have catecholamine receptors in limbic and possibly other brain structures with heightened responsiveness and that successful treatment requires desensitization of enhanced noradrenergic receptor function thus causing a reduction in the postulated amplificational mechanism that translates sensory input eventually into physiological and behavioral events.", "contents": "Functional aspects of the norepinephrine receptor coupled adenylate cyclase system in the limbic forebrain and its modification by drugs which precipitate or alleviate depression: molecular approaches to an understanding of affective disorders. The results provide evidence for a central postsynaptic regulatory mechanism involving the noradrenergic receptor coupled adenylate cyclase system. This particular system in the limbic forebrain displays properties of an adrenergic receptor with partial beta characteristics. Drugs which either can precipitate or alleviate depression in man cause time dependent opposite changes in the reactivity of this receptor system. It is tempting to speculate that depression-prone patients may have catecholamine receptors in limbic and possibly other brain structures with heightened responsiveness and that successful treatment requires desensitization of enhanced noradrenergic receptor function thus causing a reduction in the postulated amplificational mechanism that translates sensory input eventually into physiological and behavioral events."}
{"id": "PMID:204954", "title": "Tryptophan and depressive illness.", "content": "Plasma free tryptophan is significantly decreased in monopolar, depressed patients. No evidence was found to suggest that poor nutritional history prior to hospital admission was responsible for these low levels. Factors known to influence tryptophan-albumin binding in plasma, e.g. concentration of plasma proteins, albumin and non-esterified fatty acids, did not account for the low levels of free tryptophan in depressed patients. A significant decrease in plasma free tryptophan levels was found in perimenopausal but not in pre- or post-menopausal female controls. This mirrors the decrease in circulating oestrogens. Although exogenously administered oestrogens do not have any therapeutic efficacy in relieving mild residual depressive symptoms of lithium treated patients, they increased the levels of plasma free tryptophan. Clofibrate also displaces tryptophan from plasma protein binding sites in both depressed patients and controls. Utilization of the increased levels of plasma free tryptophan is reduced in depressed patients. A situation therefore exists in depressed patients where the plasma free tryptophan is not only reduced but also leaves the plasma less readily than in control subjects.", "contents": "Tryptophan and depressive illness. Plasma free tryptophan is significantly decreased in monopolar, depressed patients. No evidence was found to suggest that poor nutritional history prior to hospital admission was responsible for these low levels. Factors known to influence tryptophan-albumin binding in plasma, e.g. concentration of plasma proteins, albumin and non-esterified fatty acids, did not account for the low levels of free tryptophan in depressed patients. A significant decrease in plasma free tryptophan levels was found in perimenopausal but not in pre- or post-menopausal female controls. This mirrors the decrease in circulating oestrogens. Although exogenously administered oestrogens do not have any therapeutic efficacy in relieving mild residual depressive symptoms of lithium treated patients, they increased the levels of plasma free tryptophan. Clofibrate also displaces tryptophan from plasma protein binding sites in both depressed patients and controls. Utilization of the increased levels of plasma free tryptophan is reduced in depressed patients. A situation therefore exists in depressed patients where the plasma free tryptophan is not only reduced but also leaves the plasma less readily than in control subjects."}
{"id": "PMID:204961", "title": "Prostaglandins and sleep. Awaking effect of prostaglandins and sleep pattern of essential fatty acids deficient (EFAD) rats.", "content": "The experiments were carried out to investigate the effects of prostaglandins (PGs) on the sleep pattern in the cat, and in normal and EFAD rats. The data indicate that the duration of slow wave sleep (SWS) was significantly longer in EFAD rats compared with the normal rats. However, no difference in the REM sleep was observed between the two groups. Intraventricular (i.vc. )administration of PGE1, PGE2 and PGF2alpha increased wakefulness without a significant alteration of REM sleep. PGE1 administered i.vc. did not alter the duration of SWS or REM sleep in the chronic cat, but induced ponto-geniculo-occipital (PGO) waves (spikes) which are the phasic phenomenon of REM sleep. The fact that previous administration of 5-hydroxytryptophane abolished the PGE1-induced PGO spiking, might indicate that this drug triggered the spikes mainly via the functional inhibition of the serotonergic system.", "contents": "Prostaglandins and sleep. Awaking effect of prostaglandins and sleep pattern of essential fatty acids deficient (EFAD) rats. The experiments were carried out to investigate the effects of prostaglandins (PGs) on the sleep pattern in the cat, and in normal and EFAD rats. The data indicate that the duration of slow wave sleep (SWS) was significantly longer in EFAD rats compared with the normal rats. However, no difference in the REM sleep was observed between the two groups. Intraventricular (i.vc. )administration of PGE1, PGE2 and PGF2alpha increased wakefulness without a significant alteration of REM sleep. PGE1 administered i.vc. did not alter the duration of SWS or REM sleep in the chronic cat, but induced ponto-geniculo-occipital (PGO) waves (spikes) which are the phasic phenomenon of REM sleep. The fact that previous administration of 5-hydroxytryptophane abolished the PGE1-induced PGO spiking, might indicate that this drug triggered the spikes mainly via the functional inhibition of the serotonergic system."}
{"id": "PMID:204962", "title": "The effect of 7-oxa-13 prostynoic acid on the mechanism of action of bradykinin in human synovial fibroblasts.", "content": "Bradykinin, a potent inflammatory mediator, induces an increment in intracellular cyclic AMP concentrations of human synovial fibroblasts and evokes the synthesis and release of 3H-arachidonic acid and 3H-E prostaglandins from these cells pre-labeled in their phospholipids. Fetal calf serum in the media also stimulates the synthesis and release of these labeled lipids from pre-labeled human synovial fibroblasts and potentiates the bradykinin-induced cyclic AMP response. The PGE1 analogue, 7-oxa-13 prostynoic acid, completely abrogates both the bradykinin-induced cyclic AMP response and the bradykinin- and fetal calf serum-evoked release of labeled E-prostaglandins from pre-labeled cells. In serum-free media, the prostaglandin antagonist stimulated the release of 3H-arachidonic acid from pre-labeled human synovial fibroblasts and did not inhibit the bradykinin-induced release of this lipid.", "contents": "The effect of 7-oxa-13 prostynoic acid on the mechanism of action of bradykinin in human synovial fibroblasts. Bradykinin, a potent inflammatory mediator, induces an increment in intracellular cyclic AMP concentrations of human synovial fibroblasts and evokes the synthesis and release of 3H-arachidonic acid and 3H-E prostaglandins from these cells pre-labeled in their phospholipids. Fetal calf serum in the media also stimulates the synthesis and release of these labeled lipids from pre-labeled human synovial fibroblasts and potentiates the bradykinin-induced cyclic AMP response. The PGE1 analogue, 7-oxa-13 prostynoic acid, completely abrogates both the bradykinin-induced cyclic AMP response and the bradykinin- and fetal calf serum-evoked release of labeled E-prostaglandins from pre-labeled cells. In serum-free media, the prostaglandin antagonist stimulated the release of 3H-arachidonic acid from pre-labeled human synovial fibroblasts and did not inhibit the bradykinin-induced release of this lipid."}
{"id": "PMID:204966", "title": "Use of isoproterenol infusion to study intrapulmonary gas mixing in man.", "content": "In the present investigation, the effect of an increased cardiac output on intrapulmonary gas mixing was studied in healthy male subjects. Increase of heart rate and cardiac minute output was induced by infusion of isoproterenol, intrapulmonary gas mixing was analyzed by simultaneous washout of inert gases widely differing in molecular weight (helium and sulfur hexafluoride). Parameters, appropriate to indicate quality of gas mixing, have been crossover point (COP) and separation index (SI). During isoproterenol-induced tachycardia, the COP occurred earlier and the SI decreased. Both changes then demonstrate an improved gas intrapulmonary mixing. The movement of the heart reduces stratified inhomogeneity.", "contents": "Use of isoproterenol infusion to study intrapulmonary gas mixing in man. In the present investigation, the effect of an increased cardiac output on intrapulmonary gas mixing was studied in healthy male subjects. Increase of heart rate and cardiac minute output was induced by infusion of isoproterenol, intrapulmonary gas mixing was analyzed by simultaneous washout of inert gases widely differing in molecular weight (helium and sulfur hexafluoride). Parameters, appropriate to indicate quality of gas mixing, have been crossover point (COP) and separation index (SI). During isoproterenol-induced tachycardia, the COP occurred earlier and the SI decreased. Both changes then demonstrate an improved gas intrapulmonary mixing. The movement of the heart reduces stratified inhomogeneity."}
{"id": "PMID:204971", "title": "[Intermittent chemotherapy from the beginning or only after a period of daily administration? Quantitative bacteriological study at the initial phase of chemotherapy with INH + RMP + EMB in daily or intermittent administration].", "content": "A number of 75 adults with pulmonary tuberculosis (M. tuberculosis positive at microscopy and in cultures) were randomly selected for one of the following therapeutical regimens, administered under close surveillance in hospital during 3 months: --INH5 mg/kg body weight+RMP10 mg/kg body weight+EMB25 mg/kg body weight daily; --INH15 mg/kg body weight+RMP10 mg/kg body weight+EMB40 mg/kg body weight, intermitent administration (2/7). Disappearance of the Mycobacterium from the sputum was studied quantitatively both by microscopy and in cultures; the sputum samples were collected in the morning three days running every week during the period of 13 weeks surveillance. Processing of the results showed that in the material studied the initial intermittent administration of the drugs was just as efficient as daily administration irrespective of the criterion used for comparison (moment of negativation, rate of disappearance of the Mycobacterium and/or proportion of negative cases, dynamics of the decrease in the number of bacilli eliminated in the course of the treatment, regression of the radiologic alterations).", "contents": "[Intermittent chemotherapy from the beginning or only after a period of daily administration? Quantitative bacteriological study at the initial phase of chemotherapy with INH + RMP + EMB in daily or intermittent administration]. A number of 75 adults with pulmonary tuberculosis (M. tuberculosis positive at microscopy and in cultures) were randomly selected for one of the following therapeutical regimens, administered under close surveillance in hospital during 3 months: --INH5 mg/kg body weight+RMP10 mg/kg body weight+EMB25 mg/kg body weight daily; --INH15 mg/kg body weight+RMP10 mg/kg body weight+EMB40 mg/kg body weight, intermitent administration (2/7). Disappearance of the Mycobacterium from the sputum was studied quantitatively both by microscopy and in cultures; the sputum samples were collected in the morning three days running every week during the period of 13 weeks surveillance. Processing of the results showed that in the material studied the initial intermittent administration of the drugs was just as efficient as daily administration irrespective of the criterion used for comparison (moment of negativation, rate of disappearance of the Mycobacterium and/or proportion of negative cases, dynamics of the decrease in the number of bacilli eliminated in the course of the treatment, regression of the radiologic alterations)."}
{"id": "PMID:204972", "title": "[Epidemiological study of chronic cough and obstructive ventilatory dysfunction in a rural area].", "content": "An epidemiological study (MRC--Questionnaire and spirography) has been carried out on a population aged between 40 and 69 years living in a rural area (Coste\u015fti, district of Buz\u0103u). 440 subjects (202 men and 238 women; 83% of the population in this age group) were examined. Chronic productive cough in subjects with no other respiratory diseases was found in 8,9% of the examinated males and in 5.0% of the females. The figures are lower than those found in an urban population and in a previous survey in an other rural area. Obstructive syndrome (reduced FEV 1.0/VC ratio) was found in 5.0 and in 2.9%, respectively. More than half of the patients with obstructive syndrome had no cough; the lung function alterations found in these subjects may be due--at least in some cases--to the obstruction of distal airways which have no clinical manifestations in the early stages.", "contents": "[Epidemiological study of chronic cough and obstructive ventilatory dysfunction in a rural area]. An epidemiological study (MRC--Questionnaire and spirography) has been carried out on a population aged between 40 and 69 years living in a rural area (Coste\u015fti, district of Buz\u0103u). 440 subjects (202 men and 238 women; 83% of the population in this age group) were examined. Chronic productive cough in subjects with no other respiratory diseases was found in 8,9% of the examinated males and in 5.0% of the females. The figures are lower than those found in an urban population and in a previous survey in an other rural area. Obstructive syndrome (reduced FEV 1.0/VC ratio) was found in 5.0 and in 2.9%, respectively. More than half of the patients with obstructive syndrome had no cough; the lung function alterations found in these subjects may be due--at least in some cases--to the obstruction of distal airways which have no clinical manifestations in the early stages."}
{"id": "PMID:204973", "title": "[Post-tuberculosis syndromes in a pneumology unit].", "content": "With reference to 156 patients with a post-tuberculous syndrome, admitted to a pneumology unit, the authors discuss the anatomoclinical aspects of the primary disease and morbid entities developing against the background of the sequelae. The circumstances in which chronic bronchitis develops and post-tuberculous bronchopulmonary suppuration, frequently encountered in the pathology secondary to stable tuberculosis are analyzed. The necessity of preventing potential unspecific diseases and insuring an optimal complex treatment is emphasized.", "contents": "[Post-tuberculosis syndromes in a pneumology unit]. With reference to 156 patients with a post-tuberculous syndrome, admitted to a pneumology unit, the authors discuss the anatomoclinical aspects of the primary disease and morbid entities developing against the background of the sequelae. The circumstances in which chronic bronchitis develops and post-tuberculous bronchopulmonary suppuration, frequently encountered in the pathology secondary to stable tuberculosis are analyzed. The necessity of preventing potential unspecific diseases and insuring an optimal complex treatment is emphasized."}
{"id": "PMID:204975", "title": "[Statistico-mathematical appraisal of the length of the pretherapeutic interval in the prognosis of tubercular meningitis in children].", "content": "The data obtained concerning the two main parameters for the prognosis of tuberculous meningitis: onset-admission interval, assessed anamnestically and electtoencephalogram performed on admission, were processed mathematically by computer. The EEG is a more reliable parameter for assessing the gravity of the lesions on admission that the anammestic data regarding the onset, at a signficance threshold of 10.48% as against 5.23%. For 11.3 days there was a close correspondence between the two parameters, after which the onset-admission variable became aleatory, the only objective index of gravity being the EEG. Statistico-mathematical processing increases the objectivity and precision of the prognosis.", "contents": "[Statistico-mathematical appraisal of the length of the pretherapeutic interval in the prognosis of tubercular meningitis in children]. The data obtained concerning the two main parameters for the prognosis of tuberculous meningitis: onset-admission interval, assessed anamnestically and electtoencephalogram performed on admission, were processed mathematically by computer. The EEG is a more reliable parameter for assessing the gravity of the lesions on admission that the anammestic data regarding the onset, at a signficance threshold of 10.48% as against 5.23%. For 11.3 days there was a close correspondence between the two parameters, after which the onset-admission variable became aleatory, the only objective index of gravity being the EEG. Statistico-mathematical processing increases the objectivity and precision of the prognosis."}
{"id": "PMID:204976", "title": "[Treatment for spontaneous pneumothorax].", "content": "The present study refers to 67 cases of spontaneous pneumothorax admitted to intensive care unit. Symptomatic therapy and treatment of the pneumothorax is efficient. Minimal thoracotomy with continuous aspiration drainage indicated in severe pneumothorax and relapses after exsufflation, was considered the basic procedure in the symptomatic treatment.", "contents": "[Treatment for spontaneous pneumothorax]. The present study refers to 67 cases of spontaneous pneumothorax admitted to intensive care unit. Symptomatic therapy and treatment of the pneumothorax is efficient. Minimal thoracotomy with continuous aspiration drainage indicated in severe pneumothorax and relapses after exsufflation, was considered the basic procedure in the symptomatic treatment."}
{"id": "PMID:204974", "title": "[Bronchiectasis in advanced old-age. Etiopathogenetic and diagnostic considerations and medico-social implications].", "content": "A study was carried out on the etiopathogeny and socio-medical implications in 18 cases of bronchiectasis, without a typical clinical symptomatology before admission. All the patients were over the age of 60 years. The bronchographic examination was performed in all the cases. In 8 of the cases bronchiectasis was interpreted as a post-tuberculosis syndrome and in the other 10 cases bronchiectasis was attributed to pulmonary sclerosis of different origin (acute unsuppurated pneumopathy). The gradual changes in pulmonary mechanics, the organic and functional deficiences developing with age lowered the resistance of the body to viral and bacterial infection, contributing to the onset of bronchiectasis in the older group. The suppurative episodes were curred by treatment in all the cases.", "contents": "[Bronchiectasis in advanced old-age. Etiopathogenetic and diagnostic considerations and medico-social implications]. A study was carried out on the etiopathogeny and socio-medical implications in 18 cases of bronchiectasis, without a typical clinical symptomatology before admission. All the patients were over the age of 60 years. The bronchographic examination was performed in all the cases. In 8 of the cases bronchiectasis was interpreted as a post-tuberculosis syndrome and in the other 10 cases bronchiectasis was attributed to pulmonary sclerosis of different origin (acute unsuppurated pneumopathy). The gradual changes in pulmonary mechanics, the organic and functional deficiences developing with age lowered the resistance of the body to viral and bacterial infection, contributing to the onset of bronchiectasis in the older group. The suppurative episodes were curred by treatment in all the cases."}
{"id": "PMID:204978", "title": "[Evaluation of the epidemiological potential of patients eliminating Koch bacilli demonstrable by direct microscopic examination].", "content": "A retrospective epidemiological study was carried out on the patients in evidence since 1972-1973, following up the contacts from that time. From the data obtained it results that the proportion of contacts who contracted the disease was of 1.06% of the subjects coming in contact with cases negative at the direct microscopic examination and in cultures, 1.1% of the subjects in contact with cases negative at the direct examination but positive in cultures, and 3.9% (four times greater proportion) of the subjects in contact with bacilli eliminators, at the direct examination. The authors emphasize the simplicity and greater output of the microscopic examinations in tuberculosis.", "contents": "[Evaluation of the epidemiological potential of patients eliminating Koch bacilli demonstrable by direct microscopic examination]. A retrospective epidemiological study was carried out on the patients in evidence since 1972-1973, following up the contacts from that time. From the data obtained it results that the proportion of contacts who contracted the disease was of 1.06% of the subjects coming in contact with cases negative at the direct microscopic examination and in cultures, 1.1% of the subjects in contact with cases negative at the direct examination but positive in cultures, and 3.9% (four times greater proportion) of the subjects in contact with bacilli eliminators, at the direct examination. The authors emphasize the simplicity and greater output of the microscopic examinations in tuberculosis."}
{"id": "PMID:204977", "title": "[Technic, indications and value of pulmonary decortications (615 operated cases)].", "content": "On the basis of their experience in 615 cases of pleuropulmonary decortication, the authors discuss the indications, contraindications, approach and procedure in pleuropulmonary decortication. Surgery has the double purpose of suppressing the empyema cavity and recovering most of the functional pulmonary parenchyma. A personal procedure was applied consisting of thoracotomy through the sixth intercostal space, then along the cleavage lines outside the limits of the empyema pouch, from the periphery towards the center at the level of the pulsatile organs, zones called the key points of pleuropulmonary decortication. Very good results were obtained in 80--50% of the tuberculous empyema cases and in 90--95% of the non-tuberculous diseases. The authors consider that pleuropulmonary decortication is a widely applicable surgical method in pleural empyema, being one of the few surgical methods used for redressing the function of an organ.", "contents": "[Technic, indications and value of pulmonary decortications (615 operated cases)]. On the basis of their experience in 615 cases of pleuropulmonary decortication, the authors discuss the indications, contraindications, approach and procedure in pleuropulmonary decortication. Surgery has the double purpose of suppressing the empyema cavity and recovering most of the functional pulmonary parenchyma. A personal procedure was applied consisting of thoracotomy through the sixth intercostal space, then along the cleavage lines outside the limits of the empyema pouch, from the periphery towards the center at the level of the pulsatile organs, zones called the key points of pleuropulmonary decortication. Very good results were obtained in 80--50% of the tuberculous empyema cases and in 90--95% of the non-tuberculous diseases. The authors consider that pleuropulmonary decortication is a widely applicable surgical method in pleural empyema, being one of the few surgical methods used for redressing the function of an organ."}
{"id": "PMID:204983", "title": "B-cell activating properties of polymyxin B.", "content": "Polymyxins are known to be inhibitors of certain polyclonal B cell activators such as lipopolysaccharide and dextransulphate. However, increased specific responses to hapten-coupled mitogens have been reported after the addition of polymyxins to superoptimal conjugate doses. In this paper we have studied the effect of polymyxin B on superoptimal polyclonal doses of lipopolysaccharide. Results similar to those reported for hapten-lipopolysaccharide conjugates were obtained. Polymyxin B was also found to exert adjuvant properties for a primary immune response to sheep erythrocytes and to be a thymus-independent antigen.", "contents": "B-cell activating properties of polymyxin B. Polymyxins are known to be inhibitors of certain polyclonal B cell activators such as lipopolysaccharide and dextransulphate. However, increased specific responses to hapten-coupled mitogens have been reported after the addition of polymyxins to superoptimal conjugate doses. In this paper we have studied the effect of polymyxin B on superoptimal polyclonal doses of lipopolysaccharide. Results similar to those reported for hapten-lipopolysaccharide conjugates were obtained. Polymyxin B was also found to exert adjuvant properties for a primary immune response to sheep erythrocytes and to be a thymus-independent antigen."}
{"id": "PMID:204984", "title": "Central nervous system involvement in patients with rotavirus gastroenteritis.", "content": "Two children with rotavirus gastroenteritis are presented. The first case developed a fatal Reye's syndrome and the other one encephalitis with slow recovery. The rotavirus diagnosis was made in both cases by electron microscopy and a significant rise in antibody titres to Nebraska calf diarrhea virus was seen in one of the two patients.", "contents": "Central nervous system involvement in patients with rotavirus gastroenteritis. Two children with rotavirus gastroenteritis are presented. The first case developed a fatal Reye's syndrome and the other one encephalitis with slow recovery. The rotavirus diagnosis was made in both cases by electron microscopy and a significant rise in antibody titres to Nebraska calf diarrhea virus was seen in one of the two patients."}
{"id": "PMID:204985", "title": "Surgical treatment of simple syndactyly.", "content": "During the period 1963--74 a total of 20 operations for simple syndactyly were performed on 34 fingers. A dorsal rectangular flap and thick split skin grafts were regularly used except in 2 cases where full thickness grafts were used for covering the skin defects. There were no secondary operations. The period of observation after 13 operations was 4 years or more. It is concluded that the dorsal rectangular flap technique combined with thick split skin grafts give satisfactory results.", "contents": "Surgical treatment of simple syndactyly. During the period 1963--74 a total of 20 operations for simple syndactyly were performed on 34 fingers. A dorsal rectangular flap and thick split skin grafts were regularly used except in 2 cases where full thickness grafts were used for covering the skin defects. There were no secondary operations. The period of observation after 13 operations was 4 years or more. It is concluded that the dorsal rectangular flap technique combined with thick split skin grafts give satisfactory results."}
{"id": "PMID:204992", "title": "Autonomic receptor functions of the human ureter: an in vitro study.", "content": "The autonomic receptor functions of ureteral smooth muscle were studied in vitro on strips of human ureter obtained at surgery. A dose-dependent, reproducible, contraction response to 5-hydroxytryptamine (Serotonin, 5-HT) was demonstrated. This response could be blocked by methysergide. Responses to acetylcholine and to drugs stimulating adrenergic receptor functions were also found, but they were weak and inconsistent. This suggests that contraction of ureteral smooth muscle is mediated through receptors which are sensitive to 5-hydroxytryptamine.", "contents": "Autonomic receptor functions of the human ureter: an in vitro study. The autonomic receptor functions of ureteral smooth muscle were studied in vitro on strips of human ureter obtained at surgery. A dose-dependent, reproducible, contraction response to 5-hydroxytryptamine (Serotonin, 5-HT) was demonstrated. This response could be blocked by methysergide. Responses to acetylcholine and to drugs stimulating adrenergic receptor functions were also found, but they were weak and inconsistent. This suggests that contraction of ureteral smooth muscle is mediated through receptors which are sensitive to 5-hydroxytryptamine."}
{"id": "PMID:204993", "title": "Urinary excretion of cyclic AMP in hyperparathyroidism.", "content": "The urinary excretion of adenosine 3', 5'-monophosphate (cAMP) was investigated in 15 subjects with primary hyperparathyroidism prior to parathyroidectomy and in 13 of them also after the operation. In comparison with healthy control subjects the cAMP excretion was raised in 8 of the patients pre-operatively and after operation all values had become normal. The discriminatory value of the cAMP analyses seemed to be increased by relating the cAMP values to the urinary excretion of calcium. With the applied methods determination of urinary cAMP was superior to a radioimmunoassay of parathyroid hormone in recognizing patients with primary hyperparathyroidism. In normal subjects it appeared that the cAMP excretion expressed per gram creatinine was somewhat higher in women than in men.", "contents": "Urinary excretion of cyclic AMP in hyperparathyroidism. The urinary excretion of adenosine 3', 5'-monophosphate (cAMP) was investigated in 15 subjects with primary hyperparathyroidism prior to parathyroidectomy and in 13 of them also after the operation. In comparison with healthy control subjects the cAMP excretion was raised in 8 of the patients pre-operatively and after operation all values had become normal. The discriminatory value of the cAMP analyses seemed to be increased by relating the cAMP values to the urinary excretion of calcium. With the applied methods determination of urinary cAMP was superior to a radioimmunoassay of parathyroid hormone in recognizing patients with primary hyperparathyroidism. In normal subjects it appeared that the cAMP excretion expressed per gram creatinine was somewhat higher in women than in men."}
{"id": "PMID:204994", "title": "[The malignant neoplasm in pediatrics].", "content": "A summary of diagnostic and therapeutic progress in pediatric oncology is presented. The results are impressive, in that at least 1 child in 3 may be successfully treated. A truly effective treatment for the individual child requires the close cooperation of specialists on a national, regional and local scale. Pediatricians and general practitioners who suspect neoplasm are required, on the one hand, to ensure speedy and adequate clarification of the case, and, on the other, to cooperate in the treatment and care of children with cancer. Briefing and instruction of parents is of great practical importance.", "contents": "[The malignant neoplasm in pediatrics]. A summary of diagnostic and therapeutic progress in pediatric oncology is presented. The results are impressive, in that at least 1 child in 3 may be successfully treated. A truly effective treatment for the individual child requires the close cooperation of specialists on a national, regional and local scale. Pediatricians and general practitioners who suspect neoplasm are required, on the one hand, to ensure speedy and adequate clarification of the case, and, on the other, to cooperate in the treatment and care of children with cancer. Briefing and instruction of parents is of great practical importance."}
{"id": "PMID:204996", "title": "Preferential utilization of free cholesterol from high-density lipoproteins for biliary cholesterol secretion in man.", "content": "High- and low-density lipoproteins carrying free cholesterol labeled with 3H or 14C were administered to a patient with a bile fistula. The free cholesterol from high-density lipoproteins was more rapidly incorporated into biliary cholesterol than the free cholesterol from low-density lipoproteins. These findings show that the liver in man selectively utilizes and secretes the free cholesterol from a particular lipoprotein.", "contents": "Preferential utilization of free cholesterol from high-density lipoproteins for biliary cholesterol secretion in man. High- and low-density lipoproteins carrying free cholesterol labeled with 3H or 14C were administered to a patient with a bile fistula. The free cholesterol from high-density lipoproteins was more rapidly incorporated into biliary cholesterol than the free cholesterol from low-density lipoproteins. These findings show that the liver in man selectively utilizes and secretes the free cholesterol from a particular lipoprotein."}
{"id": "PMID:204997", "title": "Prostaglandin E1 inhibitis platelet aggregation by a pathway independent of adenosine 3',5'-monophosphate.", "content": "Aggregation of human blood platelets induced by adenosine diphosphate or 1-epinephrine was inhibited when the platelets were suspended in plasma which had been previously exposed to an insolubilized omega-aminohexylagarose derivative of prostaglandin E1. This decrease of platelet aggregation was not accompanied by a change in the concentration of adenosine 3',5'-monophosphate (cyclic AMP) in platelets. The results demonstrate the existence of an alternative pathway independent of cyclic AMP for the inhibition of platelet aggregation by plasma.", "contents": "Prostaglandin E1 inhibitis platelet aggregation by a pathway independent of adenosine 3',5'-monophosphate. Aggregation of human blood platelets induced by adenosine diphosphate or 1-epinephrine was inhibited when the platelets were suspended in plasma which had been previously exposed to an insolubilized omega-aminohexylagarose derivative of prostaglandin E1. This decrease of platelet aggregation was not accompanied by a change in the concentration of adenosine 3',5'-monophosphate (cyclic AMP) in platelets. The results demonstrate the existence of an alternative pathway independent of cyclic AMP for the inhibition of platelet aggregation by plasma."}
{"id": "PMID:204998", "title": "Different brain areas mediate the analgesic and epileptic properties of enkephalin.", "content": "Single injections of 120 micrograms of methionine-enkephalin were made into various midbrain and forebrain structures in the rat. Analgesia was observed after injections into or near the ventral, caudal midbrain periaqueductal gray matter. Seizures and other pathological electroencephalogram (EEG) changes were seen with injections into or near the forebrain dorsomedial nucleus of the thalamus. No animals with midbrain injection sites showed EEG changes, and none with forebrain injection sites were analgesic. These data, taken together with other lines of evidence, suggest that enkephalin-induced analgesia and enkephalin-induced seizures are mediated by opiate receptors that are located in different brain areas and that are pharmacologically different.", "contents": "Different brain areas mediate the analgesic and epileptic properties of enkephalin. Single injections of 120 micrograms of methionine-enkephalin were made into various midbrain and forebrain structures in the rat. Analgesia was observed after injections into or near the ventral, caudal midbrain periaqueductal gray matter. Seizures and other pathological electroencephalogram (EEG) changes were seen with injections into or near the forebrain dorsomedial nucleus of the thalamus. No animals with midbrain injection sites showed EEG changes, and none with forebrain injection sites were analgesic. These data, taken together with other lines of evidence, suggest that enkephalin-induced analgesia and enkephalin-induced seizures are mediated by opiate receptors that are located in different brain areas and that are pharmacologically different."}
{"id": "PMID:205000", "title": "Atypical lobular and papillary lesions of the breast: a follow-up study of 30 cases.", "content": "Sections from 879 consecutive breast biopsies performed for clinically and grossly benign disease between 1962 and 1966 were reviewed. Twenty-four cases of undiagnosed lobular carcinoma in situ or atypical lobular hyperplasia and six cases of intraductal papillary carcinoma were found. Only one patient later developed invasive carcinoma, an infiltrating lobular carcinoma in the ipsilateral breast, which was diagnosed seven years after the biopsy containing lobular carcinoma in situ. Invasive cancers have not been found in other patients who have a median follow-up period of eight years.", "contents": "Atypical lobular and papillary lesions of the breast: a follow-up study of 30 cases. Sections from 879 consecutive breast biopsies performed for clinically and grossly benign disease between 1962 and 1966 were reviewed. Twenty-four cases of undiagnosed lobular carcinoma in situ or atypical lobular hyperplasia and six cases of intraductal papillary carcinoma were found. Only one patient later developed invasive carcinoma, an infiltrating lobular carcinoma in the ipsilateral breast, which was diagnosed seven years after the biopsy containing lobular carcinoma in situ. Invasive cancers have not been found in other patients who have a median follow-up period of eight years."}
{"id": "PMID:205002", "title": "Idiopathic neurotrophic feet in Blacks: a pathological study.", "content": "The pathological findings in tissues obtained from 6 patients with idiopathic neurotrophic feet are described. The salient features were those of a neuropathy characterized by gross demyelinization and marked changes in the distal blood vessels. The vascular changes included medial and intimal hypertrophy with luminal narrowing. It is proposed that both the neural and the vascular changes were secondary to chronic alcoholism.", "contents": "Idiopathic neurotrophic feet in Blacks: a pathological study. The pathological findings in tissues obtained from 6 patients with idiopathic neurotrophic feet are described. The salient features were those of a neuropathy characterized by gross demyelinization and marked changes in the distal blood vessels. The vascular changes included medial and intimal hypertrophy with luminal narrowing. It is proposed that both the neural and the vascular changes were secondary to chronic alcoholism."}
{"id": "PMID:205003", "title": "The effect upon the liver of evisceration with or without hormone replacement.", "content": "All, or nearly all, of the nonhepatic splanchnic viscera were removed in dogs. In most untreated dogs, the liver cells underwent changes similar to those caused by portacaval shunt, including structural deterioration of organelles and fatty metamorphosis. The rate of division of the hepatocytes, as measured by the mitotic index and by autoradiography, was depressed as were deoxyribonucleic acid synthesis and adenylate cyclase activity. These changes were restored to, or toward, normal with the intraportal administration of commercial or purified insulin but not with glucagon or epidermal growth factor. The results of both the pathologic and biochemical studies were consistent, except for an incongruity in some of the dogs in which the colon was retained.", "contents": "The effect upon the liver of evisceration with or without hormone replacement. All, or nearly all, of the nonhepatic splanchnic viscera were removed in dogs. In most untreated dogs, the liver cells underwent changes similar to those caused by portacaval shunt, including structural deterioration of organelles and fatty metamorphosis. The rate of division of the hepatocytes, as measured by the mitotic index and by autoradiography, was depressed as were deoxyribonucleic acid synthesis and adenylate cyclase activity. These changes were restored to, or toward, normal with the intraportal administration of commercial or purified insulin but not with glucagon or epidermal growth factor. The results of both the pathologic and biochemical studies were consistent, except for an incongruity in some of the dogs in which the colon was retained."}
{"id": "PMID:205005", "title": "Middle cerebral artery occlusion within an irradiated glioblastoma multiforme.", "content": "It is rare for gliomas to involve adjacent intracranial arteries. A case of middle cerebral artery occlusion within a glioblastoma multiforme is presented.", "contents": "Middle cerebral artery occlusion within an irradiated glioblastoma multiforme. It is rare for gliomas to involve adjacent intracranial arteries. A case of middle cerebral artery occlusion within a glioblastoma multiforme is presented."}
{"id": "PMID:205009", "title": "Fine structure of rabbit articular chondrocytes in tissue culture during logarithmic and confluent stages of growth.", "content": "Ultrastructural changes in cultured articular cartilage chondrocytes from rabbit, during two growth phases were examined by transmission and scanning electron microscopy. Cells in logarithmic growth are characterized by an abundance of intracellular lipoid bodies, little development of rough endoplasmic reticulum (RER), and few cytoplasmic microfilaments. As the cells reach confluency there is a concomitant development of RER, organization and abundance of microfilaments, loss of lipoid bodies, and increase in the number of mitochondria. The fine structure of cultured chondrocytes is very similar to that of rabbit cartilage cells in situ, in that numerous lipoid bodies and microfilaments are prominent features in both cases.", "contents": "Fine structure of rabbit articular chondrocytes in tissue culture during logarithmic and confluent stages of growth. Ultrastructural changes in cultured articular cartilage chondrocytes from rabbit, during two growth phases were examined by transmission and scanning electron microscopy. Cells in logarithmic growth are characterized by an abundance of intracellular lipoid bodies, little development of rough endoplasmic reticulum (RER), and few cytoplasmic microfilaments. As the cells reach confluency there is a concomitant development of RER, organization and abundance of microfilaments, loss of lipoid bodies, and increase in the number of mitochondria. The fine structure of cultured chondrocytes is very similar to that of rabbit cartilage cells in situ, in that numerous lipoid bodies and microfilaments are prominent features in both cases."}
{"id": "PMID:205010", "title": "Scanning electron microscopy of induced cell rounding of mouse adrenal cortex tumor cells in culture.", "content": "The surface topologies of mouse adrenal cortex tumor cells of primary or clonal origin grown as monolayer cell cultures were observed by scanning electron microscopy following their exposure to substances that effect steroid release and/or cell rounding. ACTH induced cell rounding with a concomitant profuse development of fine microvilli in a non-synchronously dividing cell population. This was less pronounced with other steroidogenic substances and absent in EGTA or trypsin-treated cells. Morphological alterations occurred most rapidly with cAMP and least rapidly with dbcAMP. The rapid development of fine microvilli with ACTH is proposed to be a specific hormone mediated response.", "contents": "Scanning electron microscopy of induced cell rounding of mouse adrenal cortex tumor cells in culture. The surface topologies of mouse adrenal cortex tumor cells of primary or clonal origin grown as monolayer cell cultures were observed by scanning electron microscopy following their exposure to substances that effect steroid release and/or cell rounding. ACTH induced cell rounding with a concomitant profuse development of fine microvilli in a non-synchronously dividing cell population. This was less pronounced with other steroidogenic substances and absent in EGTA or trypsin-treated cells. Morphological alterations occurred most rapidly with cAMP and least rapidly with dbcAMP. The rapid development of fine microvilli with ACTH is proposed to be a specific hormone mediated response."}
{"id": "PMID:205012", "title": "Ultrastructure of leydig cells as revealed by secondary tissue treatment with a ferrocyanide-osmium mixture.", "content": "Leydig cells prepared routinely (glutaraldehyde--osmium) for ultrastructural studies are generally found to be lacking in subcellular detail as a result of poor membrane preservation and a dense cytoplasmic matrix. A method modified after that of Karnovsky (1971), utilizing a ferrocyanide--osmium mixture for post-treating glutaraldehyde fixed tissued, was found to yield routinely excellent preservation of Leydig cells. The primary advantages of this method were the enhancement of contrast within the Leydig cell and greatly improved membrane preservation. In addition, the smooth endoplasmic reticulum always appeared as an extensive network of interconnected tubules of uniform diameter; mitochondria, lysosomes, peroxisomes, multivesicular bodies, and Golgi were especially prominent. Glycogen and microfilaments, not readily seen in routine preparations, were found to be abundant in these cells. New observations on the numbers and distributions of subcellular organelles are described and are discussed in relation to their possible role in the steroidogenic process. In view of the greatly improved tissue preservation observed in this study, it is suggested that this treatment be used routinely for preservation of rat Leydig cells.", "contents": "Ultrastructure of leydig cells as revealed by secondary tissue treatment with a ferrocyanide-osmium mixture. Leydig cells prepared routinely (glutaraldehyde--osmium) for ultrastructural studies are generally found to be lacking in subcellular detail as a result of poor membrane preservation and a dense cytoplasmic matrix. A method modified after that of Karnovsky (1971), utilizing a ferrocyanide--osmium mixture for post-treating glutaraldehyde fixed tissued, was found to yield routinely excellent preservation of Leydig cells. The primary advantages of this method were the enhancement of contrast within the Leydig cell and greatly improved membrane preservation. In addition, the smooth endoplasmic reticulum always appeared as an extensive network of interconnected tubules of uniform diameter; mitochondria, lysosomes, peroxisomes, multivesicular bodies, and Golgi were especially prominent. Glycogen and microfilaments, not readily seen in routine preparations, were found to be abundant in these cells. New observations on the numbers and distributions of subcellular organelles are described and are discussed in relation to their possible role in the steroidogenic process. In view of the greatly improved tissue preservation observed in this study, it is suggested that this treatment be used routinely for preservation of rat Leydig cells."}
{"id": "PMID:205013", "title": "Effect of cyclic AMP on placental active transport of amino acid in rats.", "content": "In pursuit of the probable relationship of cAMP to the placental active transport of amino acids as suggested by our previous human data, experiments were done in this study with dibutyryl cAMP and theophylline loaded in pregnant rats to examine the changes in level of 14C-lysine in the maternal liver, placenta and fetus. The results are: (1) Loading of dibutyryl cAMP had no effect on the uptake of 14C-lysine in the maternal liver, placenta or fetus, except that the correction of the values with its concentration in the maternal blood revealed only a slightly significant elevation in the value in each of them 30 min after the loading. (2) Loading of theophylline significantly increased the uptake of 14C-lysine in all these organs. (3) The content of cAMP in the placenta significantly increased with the loading of theophylline. These results have led the authors to believe that endogenous cAMP is significantly linked with the placental active transport of amino acids, though there is no apparent contribution to it by exogenous cAMP.", "contents": "Effect of cyclic AMP on placental active transport of amino acid in rats. In pursuit of the probable relationship of cAMP to the placental active transport of amino acids as suggested by our previous human data, experiments were done in this study with dibutyryl cAMP and theophylline loaded in pregnant rats to examine the changes in level of 14C-lysine in the maternal liver, placenta and fetus. The results are: (1) Loading of dibutyryl cAMP had no effect on the uptake of 14C-lysine in the maternal liver, placenta or fetus, except that the correction of the values with its concentration in the maternal blood revealed only a slightly significant elevation in the value in each of them 30 min after the loading. (2) Loading of theophylline significantly increased the uptake of 14C-lysine in all these organs. (3) The content of cAMP in the placenta significantly increased with the loading of theophylline. These results have led the authors to believe that endogenous cAMP is significantly linked with the placental active transport of amino acids, though there is no apparent contribution to it by exogenous cAMP."}
{"id": "PMID:205016", "title": "Potential role of amphotericin B methyl ester in the prevention and therapy of herpetic keratitis.", "content": "Amphotericin B methyl ester (AME), a semisynthetic derivative of amphotericin B, was studied in the rabbit cornea for its potential role in prevention and therapy of HSV, vaccinia virus, and vesicular stomatitis virus. It was effective in the prevention of lesion formation by these three viruses and dose-related antiviral effects were shown. Of these viruses HSV was the most sensitive to AME. The antiviral effect of AME was additive with those of IDU and ribavirin. However, it was not effective in treating established lesions due to HSV and vaccinia virus. Since its mode of action is to bind to the sterol sites of the viral envelope, it is suggested that AME should also be effective against other enveloped DNA and RNA viruses. A new method of therapy for epithelial herpetic keratitis in humans using a combination of AME with MWD is proposed.", "contents": "Potential role of amphotericin B methyl ester in the prevention and therapy of herpetic keratitis. Amphotericin B methyl ester (AME), a semisynthetic derivative of amphotericin B, was studied in the rabbit cornea for its potential role in prevention and therapy of HSV, vaccinia virus, and vesicular stomatitis virus. It was effective in the prevention of lesion formation by these three viruses and dose-related antiviral effects were shown. Of these viruses HSV was the most sensitive to AME. The antiviral effect of AME was additive with those of IDU and ribavirin. However, it was not effective in treating established lesions due to HSV and vaccinia virus. Since its mode of action is to bind to the sterol sites of the viral envelope, it is suggested that AME should also be effective against other enveloped DNA and RNA viruses. A new method of therapy for epithelial herpetic keratitis in humans using a combination of AME with MWD is proposed."}
{"id": "PMID:205020", "title": "Prophylactic adenine arabinoside following marrow transplantation.", "content": "Interstitial pneumonia is a major cause of morbidity and mortality following allogeneic marrow transplantation for hematologic malignancy. In this prospective randomized study, 22 of 40 patients received prophylactic adenine arabinoside (Ara-A) at a dose of 5 mg/kg/day administered intravenously on an intermittent schedule. Thirteen episodes of interstitial pneumonia occurred among treated patients, including three cases associated with cytomegalovirus (CMV) in the lung. Ten episodes of interstitial pneumonia were seen in the untreated group, with CMV cultured from five. Surveillance viral cultures were positive from 18 different sites in 12 treated patients compared to 10 sites from 7 patients in the untreated group. No significant toxicity from Ara-A was encountered, and no difference in overall survival between the two groups was detected. Ara-A did not reduce the frequency of interstitial pneumonia or viral isolation from routine cultures.", "contents": "Prophylactic adenine arabinoside following marrow transplantation. Interstitial pneumonia is a major cause of morbidity and mortality following allogeneic marrow transplantation for hematologic malignancy. In this prospective randomized study, 22 of 40 patients received prophylactic adenine arabinoside (Ara-A) at a dose of 5 mg/kg/day administered intravenously on an intermittent schedule. Thirteen episodes of interstitial pneumonia occurred among treated patients, including three cases associated with cytomegalovirus (CMV) in the lung. Ten episodes of interstitial pneumonia were seen in the untreated group, with CMV cultured from five. Surveillance viral cultures were positive from 18 different sites in 12 treated patients compared to 10 sites from 7 patients in the untreated group. No significant toxicity from Ara-A was encountered, and no difference in overall survival between the two groups was detected. Ara-A did not reduce the frequency of interstitial pneumonia or viral isolation from routine cultures."}
{"id": "PMID:205027", "title": "[The cancerologically correct operation for nephroblastoma (author's transl)].", "content": "The following methodology is suitable for increasing the radicality of and the safety of the vessels during a transperitoneal operation for nephroblastoma and simultaneously for sparing the necessity of postoperative radiation: 1. primary exposure of the renal vascular cross, the vena cava, and the aorta through incision of the plica duodeno jejunalis together with mobilization of the duodenum to the right, the mesocolon to the left; 2. primary ligature of the a. renalis in front of the v. renalis (no problems on either side); 3. systematic retroperitoneal en bloc lymphodissection from the a. mesenterica superior to the forking of the aorta, laterally to the diaphragm, probative at the adnexa; 4. subsequent lateral release of the left-sided tumorous kidney, medial release of the right-sided tumorous kidney after mobilization of the cecum.", "contents": "[The cancerologically correct operation for nephroblastoma (author's transl)]. The following methodology is suitable for increasing the radicality of and the safety of the vessels during a transperitoneal operation for nephroblastoma and simultaneously for sparing the necessity of postoperative radiation: 1. primary exposure of the renal vascular cross, the vena cava, and the aorta through incision of the plica duodeno jejunalis together with mobilization of the duodenum to the right, the mesocolon to the left; 2. primary ligature of the a. renalis in front of the v. renalis (no problems on either side); 3. systematic retroperitoneal en bloc lymphodissection from the a. mesenterica superior to the forking of the aorta, laterally to the diaphragm, probative at the adnexa; 4. subsequent lateral release of the left-sided tumorous kidney, medial release of the right-sided tumorous kidney after mobilization of the cecum."}
{"id": "PMID:205028", "title": "[A new method of lymphadenography of the regional lymph nodes of the human urinary bladder. Findings relevant to cancer of the bladder (author's transl)].", "content": "Experience with and findings of a new method of indirect lymphography (endovesical lymphography) for roentgenologic visualization of lymph nodes and lymphatic vessels of the human urinary bladder are presented. After injection of Lipiodol Ultrafluid into the submucosal layer of the bladder wall all regional lymph node groups could be demonstrated. In cases of carcinoma of the bladder, endovesical lymphography provides early evidence of beginning carcinomatous infiltration of regional lymph nodes. Pedal lymphography as used thus far, provides information only about advanced lymphatic metastatic spread. It is possible that endovesical lymphography will yield new information leading to more accurate treatment of vesical carcinoma in terms of tumor staging.", "contents": "[A new method of lymphadenography of the regional lymph nodes of the human urinary bladder. Findings relevant to cancer of the bladder (author's transl)]. Experience with and findings of a new method of indirect lymphography (endovesical lymphography) for roentgenologic visualization of lymph nodes and lymphatic vessels of the human urinary bladder are presented. After injection of Lipiodol Ultrafluid into the submucosal layer of the bladder wall all regional lymph node groups could be demonstrated. In cases of carcinoma of the bladder, endovesical lymphography provides early evidence of beginning carcinomatous infiltration of regional lymph nodes. Pedal lymphography as used thus far, provides information only about advanced lymphatic metastatic spread. It is possible that endovesical lymphography will yield new information leading to more accurate treatment of vesical carcinoma in terms of tumor staging."}
{"id": "PMID:205037", "title": "Multiple endocrine cell types in thyroid medullary carcinoma. Evidence for calcitonin, somatostatin, ACTH, 5HT and small granule cells.", "content": "10 cases of thyroid medullary carcinoma (TMC) have been studied ultrastructurally and histochemically. Well differentiated calcitonin-producing C cells were present in all tumours, being prevalent in 9 cases. 5-Hydroxytryptamine (5HT) storing cells were found in two cases, somatostatin immunoreactive cells in at least 5 cases and ACTH-immunoreactive cells in 4 cases. Ultrastructurally, at least 3 types of apparently non-C cells were observed. Type 1 cells with large, poorly osmiophilic granules resembling those of gastroenteropancreatic D cells, were present in 6 cases; they appeared to correlate well with somatostatin immunoreactive cells. Type 2 cells with large osmiophilic granules were found in 5 cases; they resembled ACTH-MSH cells of the human pituitary and may correspond to the ACTH-immunoreactive cells of light microscopy. Type 3 cells with small granules and an unknown function were found in 6 cases, always in scarce number. It is concluded that TMC, although mainly made up of C cells, usually contains large proportions of other endocrine cell types.", "contents": "Multiple endocrine cell types in thyroid medullary carcinoma. Evidence for calcitonin, somatostatin, ACTH, 5HT and small granule cells. 10 cases of thyroid medullary carcinoma (TMC) have been studied ultrastructurally and histochemically. Well differentiated calcitonin-producing C cells were present in all tumours, being prevalent in 9 cases. 5-Hydroxytryptamine (5HT) storing cells were found in two cases, somatostatin immunoreactive cells in at least 5 cases and ACTH-immunoreactive cells in 4 cases. Ultrastructurally, at least 3 types of apparently non-C cells were observed. Type 1 cells with large, poorly osmiophilic granules resembling those of gastroenteropancreatic D cells, were present in 6 cases; they appeared to correlate well with somatostatin immunoreactive cells. Type 2 cells with large osmiophilic granules were found in 5 cases; they resembled ACTH-MSH cells of the human pituitary and may correspond to the ACTH-immunoreactive cells of light microscopy. Type 3 cells with small granules and an unknown function were found in 6 cases, always in scarce number. It is concluded that TMC, although mainly made up of C cells, usually contains large proportions of other endocrine cell types."}
{"id": "PMID:205039", "title": "A morphologic and morphometric study of the mitochondria in several hepatoma cell lines and in isolated hepatocytes.", "content": "Some characteristics of the mitochondria of hepatocytes and of three hepatoma cell lines have been compared. By means of stereologic analysis of electron micrographs of cross-sections through cells the volume of mitochondria per unit volume of cell cytoplasm and the surface areas of the mitochondrial envelope and cristae membranes have been measured. The relative mitochondrial volume in the cytoplasm decreases with increasing growth rate but the surface area of outer and cristae membranes per unit volume of mitochondria is not altered. The internal organization of hepatoma mitochondria, however, differs distinctly from that of normal liver mitochondria as evident from electron micrographs; the hepatoma cells contain mitochondria in which parallel cristae appear to cross the whole mitochondrial profile unlike the irregular, short cristae seen in normal liver mitochondria. Furthermore, in the fast-growing hepatoma cells the mitochondrial matrix appears less dense than in the hepatocyte. Hepatoma cells contain less organized rough endoplasmic reticulum than normal liver cells and the spatial relationship of the mitochondria to the rough cisternae, seen in the hepatocyte, is absent in the fast-growing hepatoma cell lines. It is concluded that hepatoma cells have fewer mitochondria than normal liver cells, but that the organelles have a normal content of inner membranes.", "contents": "A morphologic and morphometric study of the mitochondria in several hepatoma cell lines and in isolated hepatocytes. Some characteristics of the mitochondria of hepatocytes and of three hepatoma cell lines have been compared. By means of stereologic analysis of electron micrographs of cross-sections through cells the volume of mitochondria per unit volume of cell cytoplasm and the surface areas of the mitochondrial envelope and cristae membranes have been measured. The relative mitochondrial volume in the cytoplasm decreases with increasing growth rate but the surface area of outer and cristae membranes per unit volume of mitochondria is not altered. The internal organization of hepatoma mitochondria, however, differs distinctly from that of normal liver mitochondria as evident from electron micrographs; the hepatoma cells contain mitochondria in which parallel cristae appear to cross the whole mitochondrial profile unlike the irregular, short cristae seen in normal liver mitochondria. Furthermore, in the fast-growing hepatoma cells the mitochondrial matrix appears less dense than in the hepatocyte. Hepatoma cells contain less organized rough endoplasmic reticulum than normal liver cells and the spatial relationship of the mitochondria to the rough cisternae, seen in the hepatocyte, is absent in the fast-growing hepatoma cell lines. It is concluded that hepatoma cells have fewer mitochondria than normal liver cells, but that the organelles have a normal content of inner membranes."}
{"id": "PMID:205038", "title": "Electron Microscopy of Nephropathia Epidemica. Glomerular changes.", "content": "Electron microscopical changes in the glomeruli in 20 kidney biopsies from 18 patients, who were suffering from or had lately suffered from Nephropathia epidemica were studied. Various kinds of deposits were seen. Under the endothelial cells there were collections of light flocculent material. Small dark deposits were seen in the mesangium at the mesangial cell processes, inside the thickened basement membrane, and occasionally on the epithelial side of the membrane. Large deposits were seen around mesangial cells in the mesangium. Deposits were less numerous than in chronic immune complex diseases. The intramembranous or subepithelial deposits were associated with \"moon craters\", membranous convoluted structures or membrane debris. Granular extracellular mesangial material, round extracellular particles and intraendothelial microtubular inclusions were occasionally seen. In two of our cases occasional capsular epithelial cells showed numerous myelin bodies. Typical viruses were not seen in the glomeruli. The findings are in accord with the short period of scanty immune complex deposition in the glomeruli in the clinically active phase of Nephropathia epidemica.", "contents": "Electron Microscopy of Nephropathia Epidemica. Glomerular changes. Electron microscopical changes in the glomeruli in 20 kidney biopsies from 18 patients, who were suffering from or had lately suffered from Nephropathia epidemica were studied. Various kinds of deposits were seen. Under the endothelial cells there were collections of light flocculent material. Small dark deposits were seen in the mesangium at the mesangial cell processes, inside the thickened basement membrane, and occasionally on the epithelial side of the membrane. Large deposits were seen around mesangial cells in the mesangium. Deposits were less numerous than in chronic immune complex diseases. The intramembranous or subepithelial deposits were associated with \"moon craters\", membranous convoluted structures or membrane debris. Granular extracellular mesangial material, round extracellular particles and intraendothelial microtubular inclusions were occasionally seen. In two of our cases occasional capsular epithelial cells showed numerous myelin bodies. Typical viruses were not seen in the glomeruli. The findings are in accord with the short period of scanty immune complex deposition in the glomeruli in the clinically active phase of Nephropathia epidemica."}
{"id": "PMID:205040", "title": "Immunoelectrophoretic study of Sendae virus envelope antigens with hyperimmune sera prepared in different laboratory animals.", "content": "At similar HAI titers rabbit sera reveal a larger number of fractions (ten) in immunoelectrophoretic analysis of Sendai virus envelopes than do guinea pig sera, which only yield three distinct fractions. These differences are observed in both rocket and crossed immunoelectrophoresis, and are more marked in the latter. The number of fractions revealed does not differ in relation to the antigen used for hyperimmunization (intact Sendai virus, Triton-disrupted virus or envelope fractions extracted by Triton or Tween-ether). Solubilized Sendai virus envelopes obtained by Tween-ether or Triton treatment contain host antigens in their structure, the same as intact virus.", "contents": "Immunoelectrophoretic study of Sendae virus envelope antigens with hyperimmune sera prepared in different laboratory animals. At similar HAI titers rabbit sera reveal a larger number of fractions (ten) in immunoelectrophoretic analysis of Sendai virus envelopes than do guinea pig sera, which only yield three distinct fractions. These differences are observed in both rocket and crossed immunoelectrophoresis, and are more marked in the latter. The number of fractions revealed does not differ in relation to the antigen used for hyperimmunization (intact Sendai virus, Triton-disrupted virus or envelope fractions extracted by Triton or Tween-ether). Solubilized Sendai virus envelopes obtained by Tween-ether or Triton treatment contain host antigens in their structure, the same as intact virus."}
{"id": "PMID:205041", "title": "Chromosome abberations in rat embryo cells transformed after infection with ultraviolet-irradiated herpes simplex virus.", "content": "Two rat embryo cell lines (TR1 and TR2) transformed after infection with ultaviolet-inactivated herpes simplex virus type 2 showed modal chromosome numbers in the tetraploid range. In the TR1 cell line a near-diploid cell population replaced during subcultivation the hypotetraploid cells thus explaining the loss of immunofluorescent viral antigens. Both transformed cell lines showed frequent achromatic gaps. In the TR1 cell line such gaps were preferentially located in specific chromosome regions. The occurrence of achromatic gaps is presumably associated with the activity of a viral gene.", "contents": "Chromosome abberations in rat embryo cells transformed after infection with ultraviolet-irradiated herpes simplex virus. Two rat embryo cell lines (TR1 and TR2) transformed after infection with ultaviolet-inactivated herpes simplex virus type 2 showed modal chromosome numbers in the tetraploid range. In the TR1 cell line a near-diploid cell population replaced during subcultivation the hypotetraploid cells thus explaining the loss of immunofluorescent viral antigens. Both transformed cell lines showed frequent achromatic gaps. In the TR1 cell line such gaps were preferentially located in specific chromosome regions. The occurrence of achromatic gaps is presumably associated with the activity of a viral gene."}
{"id": "PMID:205047", "title": "[Spontaneous tumors in rats from the Rappolovo Breeding Nursery of the Academy of Medical Sciences of the USSR].", "content": "The authors report the data on the incidence of neoplasms in rats of the \"Rappolovo\" nursery breeding (USSR Acad. Med. Sci.) and their offsprings during 4 sequential generations kept in the vivarium of the N. N. Petrov Research Institute of Oncology of the USSR Ministry of Health. The frequency of spontaneous tumors in 213 male and 230 female rats was 25.8 and 35.7% accordingly. Totally, male animals developed 65 tumors, females--114. over 80% of all neoplasms developed in animals older than 18 months. The frequency of neoplasms of separate localizations in males and females was as follows: the hypophysis--7.0 and 12.6% correspondingly; the mammary gland--0.5 and 11.7%, the thyroid (thyroidal epithelium) - 1.4 and 3.0% and (light cells) 5.6 and 8.3%; the adrenal cortex--0.5 and 1.3%; the hematopoietic system --7.0 and 5.6%; parasitic sarcomas of the abdominal cavity --5.6 and 3.0%; the skin --0.4 and 0.4%; soft tissues --0.9 and 0%; the liver--0.4 and 0.4%; the kidneys --0.4 and 0.4%. Moreover, one male showed seminal vesicle tumor, and females-solitary neoplasms of the pancreas and salivary gland, the dura mater, the ovary and uterus. Significant differences were revealed in the frequency of spontaneous neoplasms in separate rat generations.", "contents": "[Spontaneous tumors in rats from the Rappolovo Breeding Nursery of the Academy of Medical Sciences of the USSR]. The authors report the data on the incidence of neoplasms in rats of the \"Rappolovo\" nursery breeding (USSR Acad. Med. Sci.) and their offsprings during 4 sequential generations kept in the vivarium of the N. N. Petrov Research Institute of Oncology of the USSR Ministry of Health. The frequency of spontaneous tumors in 213 male and 230 female rats was 25.8 and 35.7% accordingly. Totally, male animals developed 65 tumors, females--114. over 80% of all neoplasms developed in animals older than 18 months. The frequency of neoplasms of separate localizations in males and females was as follows: the hypophysis--7.0 and 12.6% correspondingly; the mammary gland--0.5 and 11.7%, the thyroid (thyroidal epithelium) - 1.4 and 3.0% and (light cells) 5.6 and 8.3%; the adrenal cortex--0.5 and 1.3%; the hematopoietic system --7.0 and 5.6%; parasitic sarcomas of the abdominal cavity --5.6 and 3.0%; the skin --0.4 and 0.4%; soft tissues --0.9 and 0%; the liver--0.4 and 0.4%; the kidneys --0.4 and 0.4%. Moreover, one male showed seminal vesicle tumor, and females-solitary neoplasms of the pancreas and salivary gland, the dura mater, the ovary and uterus. Significant differences were revealed in the frequency of spontaneous neoplasms in separate rat generations."}
{"id": "PMID:205042", "title": "The presence of complement fixing antibodies to the avian group-specific (\"gs\") sarcoma-leukosis antigen in the human population and in cancer patients.", "content": "Antibodies to the avian group-specific \"gs\" sarcoma-leukosis antigen were made evident by complement fixation reaction in human sera collected from apparently healthy subjects and from patients with different forms of cancer and non-neoplastic diseases. The number of sera investigated was of 2,123. The possible mechanisms that might account for this paraimmune response of the human organism and the prospects of developing prophylactic steps against cancer are discussed.", "contents": "The presence of complement fixing antibodies to the avian group-specific (\"gs\") sarcoma-leukosis antigen in the human population and in cancer patients. Antibodies to the avian group-specific \"gs\" sarcoma-leukosis antigen were made evident by complement fixation reaction in human sera collected from apparently healthy subjects and from patients with different forms of cancer and non-neoplastic diseases. The number of sera investigated was of 2,123. The possible mechanisms that might account for this paraimmune response of the human organism and the prospects of developing prophylactic steps against cancer are discussed."}
{"id": "PMID:205043", "title": "Investigations on the incidence of complement fixing antibodies to the avian group-specific (\"gs\") sarcoma-leukosis antigen in fowl farm workers.", "content": "The presence of complement fixing antibodies to the avian \"gs\" sarcoma-leukosis antigen is reported in the personnel of five different fowl farms. Seroconversion was observed in the workers from one of the farms, where the initial antibody incidence was very low.", "contents": "Investigations on the incidence of complement fixing antibodies to the avian group-specific (\"gs\") sarcoma-leukosis antigen in fowl farm workers. The presence of complement fixing antibodies to the avian \"gs\" sarcoma-leukosis antigen is reported in the personnel of five different fowl farms. Seroconversion was observed in the workers from one of the farms, where the initial antibody incidence was very low."}
{"id": "PMID:205044", "title": "Separation of a glycoprotein antigen for the diagnosis of bovine leukemia and some of its biochemical properties.", "content": "Data are presented on the separation and on some biochemical properties of an antigen to be used in the immunodiffusion (ID) test for detection of bovine leukemia virus. The antigen obtained proved to have the same efficiency in the ID test as a commercially available standard antigen. Experimental results suggest that the antigen is released into the culture fluid in the form of a glycoprotein molecule consisting of two subunits with a molecular weight of 60,000 linked by--SH bonds.", "contents": "Separation of a glycoprotein antigen for the diagnosis of bovine leukemia and some of its biochemical properties. Data are presented on the separation and on some biochemical properties of an antigen to be used in the immunodiffusion (ID) test for detection of bovine leukemia virus. The antigen obtained proved to have the same efficiency in the ID test as a commercially available standard antigen. Experimental results suggest that the antigen is released into the culture fluid in the form of a glycoprotein molecule consisting of two subunits with a molecular weight of 60,000 linked by--SH bonds."}
{"id": "PMID:205050", "title": "[Clinical x-ray characteristics of oat cell lung cancer].", "content": "The analysis of the case reports of 116 patients with oat-cell cancer of the lung, treated at the N. N. Petrov Research Institute of Oncology of the USSR Ministry of Health from 1952 to 1971, has revealed some features of the clinico-roentgenological picture of the disease: a short-term anamnesis, prompt development of the symptoms with predominant pains in the involved thoraic portion and retorsternally, a prevailing peribronchial growth (76.6%), early and extensive metastasization revealed in 84.5% of cases. The detection, on roentgenograms and tomograms of the chest organs, of the block of enlarged lymph nodes in the lung hilus and mediastinum in the presence of a small tumor in the lung allowed oat-cell cancer to be suspected. The roentgenological picture of median oat-cell cancer is characterized by the presence of tumor conglomerate in the lung hilus, which consisted of the primary tumor penetrating in lymph nodes adjacent to the bronchus in 66.6% of canses.", "contents": "[Clinical x-ray characteristics of oat cell lung cancer]. The analysis of the case reports of 116 patients with oat-cell cancer of the lung, treated at the N. N. Petrov Research Institute of Oncology of the USSR Ministry of Health from 1952 to 1971, has revealed some features of the clinico-roentgenological picture of the disease: a short-term anamnesis, prompt development of the symptoms with predominant pains in the involved thoraic portion and retorsternally, a prevailing peribronchial growth (76.6%), early and extensive metastasization revealed in 84.5% of cases. The detection, on roentgenograms and tomograms of the chest organs, of the block of enlarged lymph nodes in the lung hilus and mediastinum in the presence of a small tumor in the lung allowed oat-cell cancer to be suspected. The roentgenological picture of median oat-cell cancer is characterized by the presence of tumor conglomerate in the lung hilus, which consisted of the primary tumor penetrating in lymph nodes adjacent to the bronchus in 66.6% of canses."}
{"id": "PMID:205052", "title": "[A case of Klippel-Trenaunay syndrome].", "content": "The case of a 33-year-old woman suffering from the Klippel-Trenaunay-syndrome which belongs to the syndromes of dysplasia is discussed. The cases in question is an anaeviformous variant. Apart from this there exists a renal hypoplasia which is to be seen within the Klippel-Trenaunay-syndrome. This renal hypoplasia has led to a terminal renal insufficiency and has made necessary a chronic haemodialytic treatment.", "contents": "[A case of Klippel-Trenaunay syndrome]. The case of a 33-year-old woman suffering from the Klippel-Trenaunay-syndrome which belongs to the syndromes of dysplasia is discussed. The cases in question is an anaeviformous variant. Apart from this there exists a renal hypoplasia which is to be seen within the Klippel-Trenaunay-syndrome. This renal hypoplasia has led to a terminal renal insufficiency and has made necessary a chronic haemodialytic treatment."}
{"id": "PMID:205045", "title": "Interaction between ceruloplasmin and Sendai virus envelope components. Note VI. Effect of ceruloplasmin on the antigenicity of Sendai virus and subviral fractions.", "content": "The results obtained by immunization of rabbits with different Sendai virus antigens (whole virus, envelope fragments and partially purified nucleoprotein) previously incubated with homologous ceruloplasmin confirm the hypothesis of a common protein support for both hemagglutinin and neuraminidase activities, demonstrate the participation of ceruloplasmin in the immune mechanism and reveal the role of the carbohydrate moiety of the glycoprotein in immune response. The probable mechanism of interaction between ceruloplasmin and Sendai virus envelope glycoprotein is discussed.", "contents": "Interaction between ceruloplasmin and Sendai virus envelope components. Note VI. Effect of ceruloplasmin on the antigenicity of Sendai virus and subviral fractions. The results obtained by immunization of rabbits with different Sendai virus antigens (whole virus, envelope fragments and partially purified nucleoprotein) previously incubated with homologous ceruloplasmin confirm the hypothesis of a common protein support for both hemagglutinin and neuraminidase activities, demonstrate the participation of ceruloplasmin in the immune mechanism and reveal the role of the carbohydrate moiety of the glycoprotein in immune response. The probable mechanism of interaction between ceruloplasmin and Sendai virus envelope glycoprotein is discussed."}
{"id": "PMID:205061", "title": "[Seasonal changes in soil biological activity of two different forest association (author's transl)].", "content": "The biological activity of the soil under a beech forest and a spruce forest was examined in respect to the CO2-production of the soil samples, the speed of vanillin decomposition, as well as the activity of the soil enzymes catalse, saccharase and phosphatase. Both soils indicated an indentical course of seasonal activity.", "contents": "[Seasonal changes in soil biological activity of two different forest association (author's transl)]. The biological activity of the soil under a beech forest and a spruce forest was examined in respect to the CO2-production of the soil samples, the speed of vanillin decomposition, as well as the activity of the soil enzymes catalse, saccharase and phosphatase. Both soils indicated an indentical course of seasonal activity."}
{"id": "PMID:205062", "title": "A new technique of heterogenous enzyme-linked immunosorbent assay, stick-ELISA. II. Application of stick-ELISA to antigens of various infective agents.", "content": "Stick-enzyme-linked immunosorbent assay (Stick-ELISA) was applied to antigens of a variety of infective agents. An acceptable reproducibility in a series was reached, the variation coefficient being twelve percent. Preliminary results revealed that ready coated sticks could be stored at 4 degrees C for at least two to three weeks.", "contents": "A new technique of heterogenous enzyme-linked immunosorbent assay, stick-ELISA. II. Application of stick-ELISA to antigens of various infective agents. Stick-enzyme-linked immunosorbent assay (Stick-ELISA) was applied to antigens of a variety of infective agents. An acceptable reproducibility in a series was reached, the variation coefficient being twelve percent. Preliminary results revealed that ready coated sticks could be stored at 4 degrees C for at least two to three weeks."}
{"id": "PMID:205063", "title": "[Evaluation of the alginat membrane filter method for the Enterovirus concentration in water (author's transl)].", "content": "It is bound to use a concentration method for the research of enteroviruses in water. One of the concentration methods, the filtration on alginat membranes, avoids the problem of the virus elution from the filter, then the membrane is soluble in a sodium citrat buffer. This method was studied with different types of water (synthetic water, tap water and wastewater). -The recovery efficiency of Poliovirus I in clear waters (synthetic water and tap water) was poor, unsatisfying reproducible; the results are better for small virus concentrations. This efficiency may be slowly enhanced by the addition to the sample of aluminium chlorid at a final concentration of 5.10(-4) M. -The technical problems (brittleness of the membranes, slow filtrations speed, small sample volume), soon noticeable with clear waters, are more important in the case of trouble waters. Meanwhile the use of this filtration method gives better results for the recovery of Poliovirus I in wastewaters than the direct inoculation to cells cultures.", "contents": "[Evaluation of the alginat membrane filter method for the Enterovirus concentration in water (author's transl)]. It is bound to use a concentration method for the research of enteroviruses in water. One of the concentration methods, the filtration on alginat membranes, avoids the problem of the virus elution from the filter, then the membrane is soluble in a sodium citrat buffer. This method was studied with different types of water (synthetic water, tap water and wastewater). -The recovery efficiency of Poliovirus I in clear waters (synthetic water and tap water) was poor, unsatisfying reproducible; the results are better for small virus concentrations. This efficiency may be slowly enhanced by the addition to the sample of aluminium chlorid at a final concentration of 5.10(-4) M. -The technical problems (brittleness of the membranes, slow filtrations speed, small sample volume), soon noticeable with clear waters, are more important in the case of trouble waters. Meanwhile the use of this filtration method gives better results for the recovery of Poliovirus I in wastewaters than the direct inoculation to cells cultures."}
{"id": "PMID:205065", "title": "[Spontaneous intracerebral hematomas].", "content": "Within a period of five years, the authors observed 31 patients with spontaneous non-traumatic intracerebral haemorrhages. Seventeen of them were hypertensive patients. In four cases, tumour haemorrhages were found, especially in glioblastomas. In two cases, the basic disease was haemophilia and in another two cases cerebral aneurysms were found. There was one case of haemorrhagic encephalitis and one patient was being treated with anticoagulants. Eight patients died within ten days after the operation, two patients died later. The haematomas were mainly located in the temporal and parietal regions; one haematoma was found in the cerebellar hemisphere. One haematoma was detected in connection with an inoculation against influenza. In the therapy, preference is given to osteoplastic trepanation, in rare cases puncturing through a drill-hole is employed. The operation is carried out in the early phase as soon as the patient can be operated on.", "contents": "[Spontaneous intracerebral hematomas]. Within a period of five years, the authors observed 31 patients with spontaneous non-traumatic intracerebral haemorrhages. Seventeen of them were hypertensive patients. In four cases, tumour haemorrhages were found, especially in glioblastomas. In two cases, the basic disease was haemophilia and in another two cases cerebral aneurysms were found. There was one case of haemorrhagic encephalitis and one patient was being treated with anticoagulants. Eight patients died within ten days after the operation, two patients died later. The haematomas were mainly located in the temporal and parietal regions; one haematoma was found in the cerebellar hemisphere. One haematoma was detected in connection with an inoculation against influenza. In the therapy, preference is given to osteoplastic trepanation, in rare cases puncturing through a drill-hole is employed. The operation is carried out in the early phase as soon as the patient can be operated on."}
{"id": "PMID:205067", "title": "[Antiviral therapy of herpetic lesions of the nervous system].", "content": "The authors discuss some results of their study concerning the therapeutical effectiveness of different drugs and methods in treating herpes. A total of 194 patients were observed. In 73 cases desoxyribonuclease, interferon, inductors of interferon were used (viruses of ECHO of type 1 and 12, polyomyelitis vaccine, yeast ribonucleinic acid were used as inductors). Antiviral therapy permitted to prevent the development of postherpetic neuralgia, decrease the duration of hospitalization and in cases of remittent development either arrest or significantly reduce the number of relapses and clinical signs. The authors propose a scheme in the treatment of neurological forms of herpes. Further search for effective treatment is discussed.", "contents": "[Antiviral therapy of herpetic lesions of the nervous system]. The authors discuss some results of their study concerning the therapeutical effectiveness of different drugs and methods in treating herpes. A total of 194 patients were observed. In 73 cases desoxyribonuclease, interferon, inductors of interferon were used (viruses of ECHO of type 1 and 12, polyomyelitis vaccine, yeast ribonucleinic acid were used as inductors). Antiviral therapy permitted to prevent the development of postherpetic neuralgia, decrease the duration of hospitalization and in cases of remittent development either arrest or significantly reduce the number of relapses and clinical signs. The authors propose a scheme in the treatment of neurological forms of herpes. Further search for effective treatment is discussed."}
{"id": "PMID:205071", "title": "[Familial peroxidase-deficiency and acute myeloic leukemia (author's transl)].", "content": "A complete lack of myeloperoxidase (MPO) was demonstrated in a boy suffering from acute myeloic leukemia during the acute phase of the disease and after a remission was achieved. A partial defect of MPO was demonstrated in the patient's father, no further abnormalities were seen in other members of the family. The fine structure of the patient's neutrophils and monocytes appeared normal, no activity of MPO was demonstrated on the fine structural level. In the father's neutrophils transitional forms between cells exhibiting a normal MPO activity and those without activity were demonstrated. The neutrophil bactericidal activity was strongly inhibited in the patient and decreased in his father. Normal values were found in: NBT test, chemotaxis, serum-dependent phagocytosis, number of B and T lymphocytes, serum immunoglobulins, and complement. A possible connection between MPO deficiency and leukemia is discussed.", "contents": "[Familial peroxidase-deficiency and acute myeloic leukemia (author's transl)]. A complete lack of myeloperoxidase (MPO) was demonstrated in a boy suffering from acute myeloic leukemia during the acute phase of the disease and after a remission was achieved. A partial defect of MPO was demonstrated in the patient's father, no further abnormalities were seen in other members of the family. The fine structure of the patient's neutrophils and monocytes appeared normal, no activity of MPO was demonstrated on the fine structural level. In the father's neutrophils transitional forms between cells exhibiting a normal MPO activity and those without activity were demonstrated. The neutrophil bactericidal activity was strongly inhibited in the patient and decreased in his father. Normal values were found in: NBT test, chemotaxis, serum-dependent phagocytosis, number of B and T lymphocytes, serum immunoglobulins, and complement. A possible connection between MPO deficiency and leukemia is discussed."}
{"id": "PMID:205072", "title": "Regional distribution of prostaglandin-metabolizing enzymes in the mucosa of the human upper gastrointestinal tract.", "content": "The occurrence of three enzymes of prostaglandin metabolism, 15-hydroxy-prostaglandin-dehydrogenase, delta13 -reductase and prostaglandin E-9-keto-reductase was investigated in gastroscopically obtained biopsy specimens of human upper gastrointestinal mucosa. All three enzymes could be found in the mucosa of oesophagus, gastric fundus, corpus and antrum and duodenum. While the specific activity of 15-hydroxy-prostaglandin-dehydrogenase was highest and the specific activity of prostaglandin E-9-keto-reductase was lowest in all regions studied, differences of the specific activities of the enzymes between the regions are remarkably small. These results are discussed with respect to possible functions of endogenous prostaglandins in human gastrointestinal mucosa.", "contents": "Regional distribution of prostaglandin-metabolizing enzymes in the mucosa of the human upper gastrointestinal tract. The occurrence of three enzymes of prostaglandin metabolism, 15-hydroxy-prostaglandin-dehydrogenase, delta13 -reductase and prostaglandin E-9-keto-reductase was investigated in gastroscopically obtained biopsy specimens of human upper gastrointestinal mucosa. All three enzymes could be found in the mucosa of oesophagus, gastric fundus, corpus and antrum and duodenum. While the specific activity of 15-hydroxy-prostaglandin-dehydrogenase was highest and the specific activity of prostaglandin E-9-keto-reductase was lowest in all regions studied, differences of the specific activities of the enzymes between the regions are remarkably small. These results are discussed with respect to possible functions of endogenous prostaglandins in human gastrointestinal mucosa."}
{"id": "PMID:205073", "title": "[Incorporation of radioactive calcium and technetium pyrophosphate in to bones].", "content": "A method is given for simultaneous in vivo measurement of mineral and collagen metabolism of the bone. Accretion rates of 47-calcium as a chlorid into the bone are representative for bone mineralisation and of 99m-technetium labelled pyrophosphate for collagen metabolism. Compartmental models used for analysis are presented. Bone accretion rates are given in mg, or mMol respectively per unit time for the skeleton, by computation of the specific activity of 47-calcium and 99m-Technetium pyrophosphate and rational bone accretion as registered by total body profile scanning technique. The results obtained in five normal volunteers are presented.", "contents": "[Incorporation of radioactive calcium and technetium pyrophosphate in to bones]. A method is given for simultaneous in vivo measurement of mineral and collagen metabolism of the bone. Accretion rates of 47-calcium as a chlorid into the bone are representative for bone mineralisation and of 99m-technetium labelled pyrophosphate for collagen metabolism. Compartmental models used for analysis are presented. Bone accretion rates are given in mg, or mMol respectively per unit time for the skeleton, by computation of the specific activity of 47-calcium and 99m-Technetium pyrophosphate and rational bone accretion as registered by total body profile scanning technique. The results obtained in five normal volunteers are presented."}
{"id": "PMID:205074", "title": "[Chronic hypophosphatemic osteopathy (\"rachitis\"). Clinico-osteological review].", "content": "Chronic hypophosphatemia is the most common type of \"resistant\" rickets. Bone deformities, dwarfism and X-chromosomal dominant heredity, are regular findings in this \"inborn error\" of phosphate metabolism. Continumous administration of high dosage of vitamin D results in some improvement of the rickets-like bone lesions. Oral administration of phosphate seems to improve longitudinal growth. A summary of our experiences in 44 patients is presented.", "contents": "[Chronic hypophosphatemic osteopathy (\"rachitis\"). Clinico-osteological review]. Chronic hypophosphatemia is the most common type of \"resistant\" rickets. Bone deformities, dwarfism and X-chromosomal dominant heredity, are regular findings in this \"inborn error\" of phosphate metabolism. Continumous administration of high dosage of vitamin D results in some improvement of the rickets-like bone lesions. Oral administration of phosphate seems to improve longitudinal growth. A summary of our experiences in 44 patients is presented."}
{"id": "PMID:205075", "title": "[Chronic hypophosphatemic osteopathy (rachitis). Orthopedic review].", "content": "Origanized collaboration between the osteologist and the orthopaedic surgeons in diagnosis and treatment of this disease, is basically important for a successful orthopaedic approach and for the maintenance of stabile long-time healing-results. From a total of 48 patients, in 25 cases an operative treatment was necessary. The relationship between the biochemical distrubance of bone metabolism and biomechanical factors in the progressive development of articular and diaphyseal axis deformities, especially of the weight bearing lower extremities, was determined. The indications and mechanical conditions with relation to conservative and operative therapeutic procedures are analyzed and the praeoperative biomechanical and biochemical therapeutic approach is described in detail.", "contents": "[Chronic hypophosphatemic osteopathy (rachitis). Orthopedic review]. Origanized collaboration between the osteologist and the orthopaedic surgeons in diagnosis and treatment of this disease, is basically important for a successful orthopaedic approach and for the maintenance of stabile long-time healing-results. From a total of 48 patients, in 25 cases an operative treatment was necessary. The relationship between the biochemical distrubance of bone metabolism and biomechanical factors in the progressive development of articular and diaphyseal axis deformities, especially of the weight bearing lower extremities, was determined. The indications and mechanical conditions with relation to conservative and operative therapeutic procedures are analyzed and the praeoperative biomechanical and biochemical therapeutic approach is described in detail."}
{"id": "PMID:205079", "title": "Glial-mesenchymal tropism of in vivo avian sarcoma virus neuro-oncogenesis in rats.", "content": "Intracerebral inoculation of avian sarcoma virus (ASV) in postnatal animals induces gliomas and sarcomas but no neuronal tumors. High titer Bratislava-77 strain ASV was inoculated intracerebrally in fetal F-344 rats between 17 and 20 days of gestation: a time of active neuronal proliferation. Following birth inoculated rats developed gliomas and sarcomas but no neuronal tumors. The results are evidence that the glial-mesenchymal tropism of in vivo ASV neuro-oncogenesis is independent of stage of neurocytodifferentiation at inoculation.", "contents": "Glial-mesenchymal tropism of in vivo avian sarcoma virus neuro-oncogenesis in rats. Intracerebral inoculation of avian sarcoma virus (ASV) in postnatal animals induces gliomas and sarcomas but no neuronal tumors. High titer Bratislava-77 strain ASV was inoculated intracerebrally in fetal F-344 rats between 17 and 20 days of gestation: a time of active neuronal proliferation. Following birth inoculated rats developed gliomas and sarcomas but no neuronal tumors. The results are evidence that the glial-mesenchymal tropism of in vivo ASV neuro-oncogenesis is independent of stage of neurocytodifferentiation at inoculation."}
{"id": "PMID:205080", "title": "Cell membrane structure of human giant-celled glioblastoma.", "content": "A giant-cell glioblastoma was examined by electron microscopy and by the freeze-fracture technique. The cell membranes bordering the extensive extracellular space often showed complicated undulations and peripheral vacuoles as well as occasional microvilli or filopodia. The undulations were mainly composed of plasmalemmal vesicles as well as of large (400--800 nm in diameter) and small (30--50 nm in diameter) localized protrusions and invaginations of the cell membrane. Deep invaginations of the cell membrane apparently resulted in two separate cytoplasmic portions. Locking of protruded cytoplasmic tongues and adherens junctions were sometimes seen in closely approximated cell membranes. The average number of membrane particles per micrometer2 was 630 +/- 130 on the P face and 180 +/- 30 on the E face. The membrane particles were occasionally aggregated to form clusters about 30 to 150 micrometer in diameter. Gap junctions were occasionally found, but there were no tight junctions. Large particles about 30 nm in diameter were found in places.", "contents": "Cell membrane structure of human giant-celled glioblastoma. A giant-cell glioblastoma was examined by electron microscopy and by the freeze-fracture technique. The cell membranes bordering the extensive extracellular space often showed complicated undulations and peripheral vacuoles as well as occasional microvilli or filopodia. The undulations were mainly composed of plasmalemmal vesicles as well as of large (400--800 nm in diameter) and small (30--50 nm in diameter) localized protrusions and invaginations of the cell membrane. Deep invaginations of the cell membrane apparently resulted in two separate cytoplasmic portions. Locking of protruded cytoplasmic tongues and adherens junctions were sometimes seen in closely approximated cell membranes. The average number of membrane particles per micrometer2 was 630 +/- 130 on the P face and 180 +/- 30 on the E face. The membrane particles were occasionally aggregated to form clusters about 30 to 150 micrometer in diameter. Gap junctions were occasionally found, but there were no tight junctions. Large particles about 30 nm in diameter were found in places."}
{"id": "PMID:205082", "title": "Endoneurial pressure in hexachlorophene neuropathy.", "content": "Increased endoneurial pressure of up to 17.0 cm H2O was recorded in the peripheral nerves of rats fed hexachlorophene in their laboratory diet. The pressure was measured using a micropressure transducer developed for recording pressure in the microcirculation. The results were correlated with morphologic findings. Teased nerve fibers and araldite-embedded specimens of hexachlorophene damaged sciatic nerve revealed the characteristic severe intramyelinic edema due to splits in the minor dense lines of compact myelin giving rise to wide interlamellar spaces as shown in previous studies. The endoneurial pressure of rats exposed to hexachlorophene for 11 days and subsequently fed a normal diet returned to normal (0.2-3.0 cm H2O) after 12 days, and morphologic examination showed few residual abnormalities. Prolonged exposure to hexachlorophene for up to 4 weeks caused widespread axonal degeneration in addition to intramyelinic edema. Animals treated with hexachlorophene for 21 days followed by a normal diet for 14 days showed degenerated axons, phagocytosis of myelin as well as interstitial edema and elevated endoneurial pressure. It is suggested that axonal degeneration in hexachlorophene neuropathy is caused by increased endoneurial pressure.", "contents": "Endoneurial pressure in hexachlorophene neuropathy. Increased endoneurial pressure of up to 17.0 cm H2O was recorded in the peripheral nerves of rats fed hexachlorophene in their laboratory diet. The pressure was measured using a micropressure transducer developed for recording pressure in the microcirculation. The results were correlated with morphologic findings. Teased nerve fibers and araldite-embedded specimens of hexachlorophene damaged sciatic nerve revealed the characteristic severe intramyelinic edema due to splits in the minor dense lines of compact myelin giving rise to wide interlamellar spaces as shown in previous studies. The endoneurial pressure of rats exposed to hexachlorophene for 11 days and subsequently fed a normal diet returned to normal (0.2-3.0 cm H2O) after 12 days, and morphologic examination showed few residual abnormalities. Prolonged exposure to hexachlorophene for up to 4 weeks caused widespread axonal degeneration in addition to intramyelinic edema. Animals treated with hexachlorophene for 21 days followed by a normal diet for 14 days showed degenerated axons, phagocytosis of myelin as well as interstitial edema and elevated endoneurial pressure. It is suggested that axonal degeneration in hexachlorophene neuropathy is caused by increased endoneurial pressure."}
{"id": "PMID:205084", "title": "No demonstrable accumulation of 14C-vitamin D3 in developing rat teeth and bones.", "content": "The distribution of 14C-vitamin D3 administered subcutaneously in arachidic oil to 6-day-old suckling rats has been examined autoradiographically. The animals were sacrificed 1, 2, 4 and 8 days after injection. The autoradiographic exposure time was 4 months. The sectioning and exposure was performed in a freeze-room. Radioactivity was found mainly in the liver, kidney, intestines and fat depots. No uptake was found in developing teeth or bones.", "contents": "No demonstrable accumulation of 14C-vitamin D3 in developing rat teeth and bones. The distribution of 14C-vitamin D3 administered subcutaneously in arachidic oil to 6-day-old suckling rats has been examined autoradiographically. The animals were sacrificed 1, 2, 4 and 8 days after injection. The autoradiographic exposure time was 4 months. The sectioning and exposure was performed in a freeze-room. Radioactivity was found mainly in the liver, kidney, intestines and fat depots. No uptake was found in developing teeth or bones."}
{"id": "PMID:205083", "title": "Idiopathic Parkinsonism with Lewy-type inclusions in cerebral cortex. A case report.", "content": "A case of idiopathic parkinsonism showed specific neuropathological findings, namely, the diffuse appearances of intracytoplasmic inclusions of Lewy type in the cerebral cortex in addition to many Lewy bodies in the pigmented brain stem nuclei. The staining properties and the ultrastructure of the inclusions in the cerebral cortex had a strong resemblance to those of the Lewy bodies in the substantia nigra, though a few electron microscopical differences were observed. Almost all of these 'cortical inclusions' were homogeneous or had an obscure core in their center, and they gave the impression of immature Lewy bodies.", "contents": "Idiopathic Parkinsonism with Lewy-type inclusions in cerebral cortex. A case report. A case of idiopathic parkinsonism showed specific neuropathological findings, namely, the diffuse appearances of intracytoplasmic inclusions of Lewy type in the cerebral cortex in addition to many Lewy bodies in the pigmented brain stem nuclei. The staining properties and the ultrastructure of the inclusions in the cerebral cortex had a strong resemblance to those of the Lewy bodies in the substantia nigra, though a few electron microscopical differences were observed. Almost all of these 'cortical inclusions' were homogeneous or had an obscure core in their center, and they gave the impression of immature Lewy bodies."}
{"id": "PMID:205086", "title": "Subacute sclerosing panencephalitis with special reference to the ultrastructure of inclusions in the brain and lung.", "content": "A 7-year-old boy, who was diagnosed as typical SSPE by clinical data and laboratory findings, was autopsied and observed by immunofluorescent techniques, light and electron microscope. The morphological characteristics in the brain were perivascular cuffings with plasma cells, lymphocytes and mononuclear cells, gliosis and a large number of intranuclear and intracytoplasmic inclusions in the neuroglias and nerve cells. Various kinds of intranuclear inclusions were elucidated by electron microscopy and the fin structures of these inclusions were described in detail. At least five types of intranuclear inclusions were regarded as specific in SSPE. The presence of intranuclear inclusions of mononuclear cells in the lungs resembling the inclusions in the neuroglias suggested that the disease was not localized in the brain but could be disseminated throughout the body.", "contents": "Subacute sclerosing panencephalitis with special reference to the ultrastructure of inclusions in the brain and lung. A 7-year-old boy, who was diagnosed as typical SSPE by clinical data and laboratory findings, was autopsied and observed by immunofluorescent techniques, light and electron microscope. The morphological characteristics in the brain were perivascular cuffings with plasma cells, lymphocytes and mononuclear cells, gliosis and a large number of intranuclear and intracytoplasmic inclusions in the neuroglias and nerve cells. Various kinds of intranuclear inclusions were elucidated by electron microscopy and the fin structures of these inclusions were described in detail. At least five types of intranuclear inclusions were regarded as specific in SSPE. The presence of intranuclear inclusions of mononuclear cells in the lungs resembling the inclusions in the neuroglias suggested that the disease was not localized in the brain but could be disseminated throughout the body."}
{"id": "PMID:205087", "title": "Childhood coronary sclerosis.", "content": "Childhood coronary sclerosis was studied histologically, histochemically immunohistochemically and biochemically on 60 autopsy cases aged from new-born to 20 years. Intimal thickening often started even in the newborn babies particularly at branching or bending points of the arteries, where fibrocellular proliferation with acid mucopolysaccharide accumulation was the main histological feature. Microthrombi were occasionally demonstrated even in infants, and fatty streaks appeared generally in the second decade. Microthrombi were usually smaller and fewer than fatty streaks. Beta-lipoprotein and fibrinogen infiltrations into intima were proven in some cases. Mural vascularization was occasionally observed especially in the areas beneath intimal thickening. Pressure effect of the blood stream and anatomically specific points in the arteries seemed to be important as initial factors of coronary sclerosis, where plasma constituents might pass in an easier manner into intimas by increased permeability. Secondarily mural capillaries might play some role in developing atheromas which would produce an eccentrically located luminal obstruction later in adulthood, by local circulatory disturbances within the arterial walls.", "contents": "Childhood coronary sclerosis. Childhood coronary sclerosis was studied histologically, histochemically immunohistochemically and biochemically on 60 autopsy cases aged from new-born to 20 years. Intimal thickening often started even in the newborn babies particularly at branching or bending points of the arteries, where fibrocellular proliferation with acid mucopolysaccharide accumulation was the main histological feature. Microthrombi were occasionally demonstrated even in infants, and fatty streaks appeared generally in the second decade. Microthrombi were usually smaller and fewer than fatty streaks. Beta-lipoprotein and fibrinogen infiltrations into intima were proven in some cases. Mural vascularization was occasionally observed especially in the areas beneath intimal thickening. Pressure effect of the blood stream and anatomically specific points in the arteries seemed to be important as initial factors of coronary sclerosis, where plasma constituents might pass in an easier manner into intimas by increased permeability. Secondarily mural capillaries might play some role in developing atheromas which would produce an eccentrically located luminal obstruction later in adulthood, by local circulatory disturbances within the arterial walls."}
{"id": "PMID:205088", "title": "Trophoblastic pseudotumour of the uterus. A case report.", "content": "A 52-year-old woman with vaginal bleedings had hysterectomy because curettings prompted suspicion of malignancy. A uterine tumour with deep infiltration of trophoblastic cells in the myometrium was revealed. Postoperative quantitative analysis for urinary human choriongonadotropin gave 1500 IU/1. The patient got no other treatment and is well 3 years after operation. The histopathological picture and the clinical course were consistent with the recently introduced diagnosis of benign \"trophoblastic pseudotumour\", which should perhaps replace the old terms \"syncytioma\" and \"chorionepitheliosis\".", "contents": "Trophoblastic pseudotumour of the uterus. A case report. A 52-year-old woman with vaginal bleedings had hysterectomy because curettings prompted suspicion of malignancy. A uterine tumour with deep infiltration of trophoblastic cells in the myometrium was revealed. Postoperative quantitative analysis for urinary human choriongonadotropin gave 1500 IU/1. The patient got no other treatment and is well 3 years after operation. The histopathological picture and the clinical course were consistent with the recently introduced diagnosis of benign \"trophoblastic pseudotumour\", which should perhaps replace the old terms \"syncytioma\" and \"chorionepitheliosis\"."}
{"id": "PMID:205089", "title": "An analysis of 38 malignant fibrous histiocytomas in the extremities.", "content": "All the malignant soft tissue tumours in the extremities and limb girdles reported to the Finnish Cancer Registry between 1960-1969 were reviewed. From a total of 246 sarcomas, 38 were diagnosed as malignant fibrous histiocytoma. There was an equal number of male and female patients with the median age of 67 years. The thigh was the most frequent site, and the majority of the tumours originated in the deep soft tissues. The predominant treatment was excision followed by radiation therapy. In 17 patients there were one or more recurrences and in 21 patients there was a metastatic spread ascertained by biopsy, autopsy or clinical or radiographic evidence. There were 11 survivors with a minimum of 5 years' follow-up; seven patients died of an intercurrent disease and the remaining 20 patients were considered victims of their tumour. The findings that seemed to favour a poor prognosis were higher age and female sex of the patient as well as deep location, large size, necrotic areas, and high mitotic activity of the tumour.", "contents": "An analysis of 38 malignant fibrous histiocytomas in the extremities. All the malignant soft tissue tumours in the extremities and limb girdles reported to the Finnish Cancer Registry between 1960-1969 were reviewed. From a total of 246 sarcomas, 38 were diagnosed as malignant fibrous histiocytoma. There was an equal number of male and female patients with the median age of 67 years. The thigh was the most frequent site, and the majority of the tumours originated in the deep soft tissues. The predominant treatment was excision followed by radiation therapy. In 17 patients there were one or more recurrences and in 21 patients there was a metastatic spread ascertained by biopsy, autopsy or clinical or radiographic evidence. There were 11 survivors with a minimum of 5 years' follow-up; seven patients died of an intercurrent disease and the remaining 20 patients were considered victims of their tumour. The findings that seemed to favour a poor prognosis were higher age and female sex of the patient as well as deep location, large size, necrotic areas, and high mitotic activity of the tumour."}
{"id": "PMID:205090", "title": "Biochemical and morphological characterization of subcellular fractions isolated from rabbit colon muscle.", "content": "From a homogenate of rabbit colon muscle subcellular fractions were isolated by differential centrifugation. The crude microsomal fraction could be separated into subfractions, a fraction of vesicular microsomes at 35% sucrose, a fraction containing sarcolemma, mitochondrial fragments and microsomal vesicles at 35--45% sucrose and a small protein fraction at 45--55% sucrose. Their biochemical properties and their morphological characterization were investigated. The cholesterol and the phospholipid content was equally distributed between the microsomal fractions 35% and 35--45% while the RNA was localized to the mitochondria and the microsomal fraction 35%. The enzyme cytochrome c oxidase was found to be concentrated in the mitochondria while a high contamination was found in the microsomal fractions 35--45%. The NADH-oxidase activity was highest in the 35% fraction and the 5'-nucleotidase activity in the 40,000 X g supernatant. The microsomal subfractions contained the enzymes ATPase, adenylate cyclase and phosphodiesterase. In the 35% fraction Ca stimulated the hydrolysis of ATP. The binding of [3H]-ouabain and the incorporation of [3H]-leucine was most pronounced in the 35% fraction. In a K+-free Krebs Ringer medium the binding of the glucoside was stimulated in all the fractions. From these results we concluded that the fraction 35% sucrose may be mainly derived from the endoplasmic reticulum and the plasma membrane while the 35--45% originates from the plasma membrane, mitochondria and to a lesser extent the endoplasmic reticulum.", "contents": "Biochemical and morphological characterization of subcellular fractions isolated from rabbit colon muscle. From a homogenate of rabbit colon muscle subcellular fractions were isolated by differential centrifugation. The crude microsomal fraction could be separated into subfractions, a fraction of vesicular microsomes at 35% sucrose, a fraction containing sarcolemma, mitochondrial fragments and microsomal vesicles at 35--45% sucrose and a small protein fraction at 45--55% sucrose. Their biochemical properties and their morphological characterization were investigated. The cholesterol and the phospholipid content was equally distributed between the microsomal fractions 35% and 35--45% while the RNA was localized to the mitochondria and the microsomal fraction 35%. The enzyme cytochrome c oxidase was found to be concentrated in the mitochondria while a high contamination was found in the microsomal fractions 35--45%. The NADH-oxidase activity was highest in the 35% fraction and the 5'-nucleotidase activity in the 40,000 X g supernatant. The microsomal subfractions contained the enzymes ATPase, adenylate cyclase and phosphodiesterase. In the 35% fraction Ca stimulated the hydrolysis of ATP. The binding of [3H]-ouabain and the incorporation of [3H]-leucine was most pronounced in the 35% fraction. In a K+-free Krebs Ringer medium the binding of the glucoside was stimulated in all the fractions. From these results we concluded that the fraction 35% sucrose may be mainly derived from the endoplasmic reticulum and the plasma membrane while the 35--45% originates from the plasma membrane, mitochondria and to a lesser extent the endoplasmic reticulum."}
{"id": "PMID:205092", "title": "Primary culture of adult rat liver cells. I. Preparation of isolated cells from trypsin-perfused liver of adult rat.", "content": "Isolated hepatic cells from adult rats were prepared by perfusing the livers with trypsin. The highest yield of viable cells was obtained by perfusing the liver with 0.1% trypsin, pH 7.0, at 37 degrees C for 30 min. Following this treatment about 70% of cells excluded trypan blue. The isolated cells contained many binucleate cells. Between 60 and 70% of DNA present originally in the liver was recovered from the isolated hepatic cells, which had higher glucose 6-phosphatase activity than the liver. Thus the resulting cell population seems to be rich in hepatocytes. The isolated hepatic cells, however, lost some of their cellular proteins such as alanine and tyrosine amino-transferases. It was suggested that the membranes of isolated hepatic cells might be damaged by both enzymatic digestion and mechanical destruction.", "contents": "Primary culture of adult rat liver cells. I. Preparation of isolated cells from trypsin-perfused liver of adult rat. Isolated hepatic cells from adult rats were prepared by perfusing the livers with trypsin. The highest yield of viable cells was obtained by perfusing the liver with 0.1% trypsin, pH 7.0, at 37 degrees C for 30 min. Following this treatment about 70% of cells excluded trypan blue. The isolated cells contained many binucleate cells. Between 60 and 70% of DNA present originally in the liver was recovered from the isolated hepatic cells, which had higher glucose 6-phosphatase activity than the liver. Thus the resulting cell population seems to be rich in hepatocytes. The isolated hepatic cells, however, lost some of their cellular proteins such as alanine and tyrosine amino-transferases. It was suggested that the membranes of isolated hepatic cells might be damaged by both enzymatic digestion and mechanical destruction."}
{"id": "PMID:205085", "title": "A clinical pilot study on preformed autologous ossicles. II.", "content": "A research project concerning performed autologous ossicles has been going on for more than ten years. Animal experimental studies were followed by a clinical pilot study which showed that bone could be produced in a titanium mould placed in the proximal tibia metaphysis. In the present investigation, in which another five patients were operated on, the experimental design was changed compared to the first pilot study and bone production was improved. In addition to the tibial moulds ten titanium cylinders were placed around a bony bridge prepared in the linea temporalis of the ear to be reconstructed. Nine out of ten of these cylinders contained bone suitable for ossiculoplasty. Histology showed higher osteocyte density and a higher proportion of vital looking osteocytes in the performed grafts compared with a peroperatively sculptured graft of cortical bone. On histochemical investigation the performed graft cells seemed viable at the time of transplantation. The technique for obtaining a preformed autologous ossicle through the titanium cylinders in the temporal bone was easy to perform and the patients did not experience any discomfort. The risk of infection in this area was judged to be small.", "contents": "A clinical pilot study on preformed autologous ossicles. II. A research project concerning performed autologous ossicles has been going on for more than ten years. Animal experimental studies were followed by a clinical pilot study which showed that bone could be produced in a titanium mould placed in the proximal tibia metaphysis. In the present investigation, in which another five patients were operated on, the experimental design was changed compared to the first pilot study and bone production was improved. In addition to the tibial moulds ten titanium cylinders were placed around a bony bridge prepared in the linea temporalis of the ear to be reconstructed. Nine out of ten of these cylinders contained bone suitable for ossiculoplasty. Histology showed higher osteocyte density and a higher proportion of vital looking osteocytes in the performed grafts compared with a peroperatively sculptured graft of cortical bone. On histochemical investigation the performed graft cells seemed viable at the time of transplantation. The technique for obtaining a preformed autologous ossicle through the titanium cylinders in the temporal bone was easy to perform and the patients did not experience any discomfort. The risk of infection in this area was judged to be small."}
{"id": "PMID:205093", "title": "Simian virus 40 chromatin showing nucleosomes in linear bead-like arrangements along extended closed circular DNA.", "content": "Viral nucleoprotein complexes were extracted from nuclei of permissive cells (CV-1) infected with simian virus 40 (SV40) and examined by electron microscopy. SV40 nucleoprotein complexes (SV40 chromatin) showed nucleosomes in linear bead-like arrangements along the extended closed circular DNA. The contour length of the SV40 chromatin was only 1.0-1.8 times shorter than that of viral DNA obtained after deproteinization. The data suggest that the circular DNA in SV40 chromatin can be extended to nearly its full length without detachment of the histone complexes.", "contents": "Simian virus 40 chromatin showing nucleosomes in linear bead-like arrangements along extended closed circular DNA. Viral nucleoprotein complexes were extracted from nuclei of permissive cells (CV-1) infected with simian virus 40 (SV40) and examined by electron microscopy. SV40 nucleoprotein complexes (SV40 chromatin) showed nucleosomes in linear bead-like arrangements along the extended closed circular DNA. The contour length of the SV40 chromatin was only 1.0-1.8 times shorter than that of viral DNA obtained after deproteinization. The data suggest that the circular DNA in SV40 chromatin can be extended to nearly its full length without detachment of the histone complexes."}
{"id": "PMID:205101", "title": "Regulation of macromolecular synthesis in Morris hepatomas.", "content": "In this review, some studies are discussed in which an attempt has been made to determine the nature of changes in macromolecular synthesis in Morris hepatomas. The incorporation of isotope labeled precursors into nucleic acids and proteins has suggested greatly increased rates of DNA synthesis in comparison with rat liver of normal and tumor bearing rats, but for RNA and proteins the changes may be impressive for individual macromolecular species but total synthesis is not greatly changed. Fractionation of nuclear proteins has indicated altered patterns of synthesis which are related to the growth rates of the tumors and are much more pronounced than in regenerating liver despite a growth rate similar to that of the most rapidly growing hepatomas. Investigations with drugs which inhibit synthesis of macromolecules has suggested that liver neoplasia may be accompanied by changes in response which may make the tumor less sensitive or more sensitive to regulation than the tissue of origin.", "contents": "Regulation of macromolecular synthesis in Morris hepatomas. In this review, some studies are discussed in which an attempt has been made to determine the nature of changes in macromolecular synthesis in Morris hepatomas. The incorporation of isotope labeled precursors into nucleic acids and proteins has suggested greatly increased rates of DNA synthesis in comparison with rat liver of normal and tumor bearing rats, but for RNA and proteins the changes may be impressive for individual macromolecular species but total synthesis is not greatly changed. Fractionation of nuclear proteins has indicated altered patterns of synthesis which are related to the growth rates of the tumors and are much more pronounced than in regenerating liver despite a growth rate similar to that of the most rapidly growing hepatomas. Investigations with drugs which inhibit synthesis of macromolecules has suggested that liver neoplasia may be accompanied by changes in response which may make the tumor less sensitive or more sensitive to regulation than the tissue of origin."}
{"id": "PMID:205115", "title": "The receptor concept: prejudice, prediction, and paradox.", "content": "Major  progress has been achieved in understanding the chemical nature of receptors for certain hormones and neurotransmitters. Some of these units have been obtained as homogenous proteins; concept and technology are adequate to permit the detailed chemical and structural analysis of these macromolecular units. The critical problem which now arises is to define how a receptor once \"occupied\" and \"activated\" serves to initiate action. Elucidation of details of receptor structure, in of itself, will not solve the \"coupling problem\" in hormone action. New concepts, as well as new technics, will probably be necessary. In this discussion I have raised the possibility that metals coordinated to hormone receptor complexes may be the \"trigger\" element involved in initiating action, serving to alter the state of functional units in binary fashion. In effect, the metal determines whether the \"state\" of the system is active or inactive. As stated previously in connection with the action of steroid hormone receptor complexes, the specific suggestions made relating metals to the hormone coulping process have been advanced primarily to illustrate the conceptual gap which exists with respect to \"coupling.\" The present suggestions may prove to be correct or untenable, in whole or in part. If it turns out that metals play a central role in the coupling process of hormone action, perhaps via completely different mechanisms than those suggested here, one of the central ideas of receptor action developed by the pioneers who created the receptor concept will have been resurrected in principle, if not in detail. In science, as in life generally, conceptual progress once achieved sometimes turns out to be the rediscovery of the past.", "contents": "The receptor concept: prejudice, prediction, and paradox. Major  progress has been achieved in understanding the chemical nature of receptors for certain hormones and neurotransmitters. Some of these units have been obtained as homogenous proteins; concept and technology are adequate to permit the detailed chemical and structural analysis of these macromolecular units. The critical problem which now arises is to define how a receptor once \"occupied\" and \"activated\" serves to initiate action. Elucidation of details of receptor structure, in of itself, will not solve the \"coupling problem\" in hormone action. New concepts, as well as new technics, will probably be necessary. In this discussion I have raised the possibility that metals coordinated to hormone receptor complexes may be the \"trigger\" element involved in initiating action, serving to alter the state of functional units in binary fashion. In effect, the metal determines whether the \"state\" of the system is active or inactive. As stated previously in connection with the action of steroid hormone receptor complexes, the specific suggestions made relating metals to the hormone coulping process have been advanced primarily to illustrate the conceptual gap which exists with respect to \"coupling.\" The present suggestions may prove to be correct or untenable, in whole or in part. If it turns out that metals play a central role in the coupling process of hormone action, perhaps via completely different mechanisms than those suggested here, one of the central ideas of receptor action developed by the pioneers who created the receptor concept will have been resurrected in principle, if not in detail. In science, as in life generally, conceptual progress once achieved sometimes turns out to be the rediscovery of the past."}
{"id": "PMID:205109", "title": "The synthesis and secretion of serum albumin in Morris hepatomas 5123tc and 9121.", "content": "In vivo, Morris hepatomas 5123tc and 9121 do not secrete serum proteins into the bloodstream. However, they synthesize albumin, at a reduced rate, if compared with liver. The produced albumin accumulates, leading to an enlargement of the Golgi apparatus and the appearance of intracellular vesicles. The proportion and the absolute amount of albumin found within the hepatoma cells is increased compared with liver. As described recently for liver in vivo and for hepatocyte suspensions, albumin is synthesized also in hepatoma cells via a precursor protein. Hepatoma cells in culture secrete albumin into the medium. However, albumin accumulates in the cells with time in culture, indicating again a limited secretory capacity of the hepatoma cell.", "contents": "The synthesis and secretion of serum albumin in Morris hepatomas 5123tc and 9121. In vivo, Morris hepatomas 5123tc and 9121 do not secrete serum proteins into the bloodstream. However, they synthesize albumin, at a reduced rate, if compared with liver. The produced albumin accumulates, leading to an enlargement of the Golgi apparatus and the appearance of intracellular vesicles. The proportion and the absolute amount of albumin found within the hepatoma cells is increased compared with liver. As described recently for liver in vivo and for hepatocyte suspensions, albumin is synthesized also in hepatoma cells via a precursor protein. Hepatoma cells in culture secrete albumin into the medium. However, albumin accumulates in the cells with time in culture, indicating again a limited secretory capacity of the hepatoma cell."}
{"id": "PMID:205119", "title": "Components of the renin-angiotensin system in the plasma of Bothrops jararaca.", "content": "By means of high voltage electrophoresis experiments it could be demonstrated that the dipeptide hydrolase present in the plasma of Bothrops jararaca is similar to the angiotensin I converting enzyme of human plasma. Therefore, angiotensin I can be considered as a probable natural substrate for this potent snake peptidase in contrast to bradykinin, which is excluded in that case, since this snake plasma was previously found to be deficient in intrinsic kinin releasing system. On the other hand, the presence of angiotensinase activity in this snake plasma could also be demonstrated. Through the pharmacological comparison of angiotensin II with the pressor peptide released from the Bothrops jararaca plasma by chymotrypsin, an indirect indication of the presence of angiotensinogen in the plasma of this reptile was obtained.", "contents": "Components of the renin-angiotensin system in the plasma of Bothrops jararaca. By means of high voltage electrophoresis experiments it could be demonstrated that the dipeptide hydrolase present in the plasma of Bothrops jararaca is similar to the angiotensin I converting enzyme of human plasma. Therefore, angiotensin I can be considered as a probable natural substrate for this potent snake peptidase in contrast to bradykinin, which is excluded in that case, since this snake plasma was previously found to be deficient in intrinsic kinin releasing system. On the other hand, the presence of angiotensinase activity in this snake plasma could also be demonstrated. Through the pharmacological comparison of angiotensin II with the pressor peptide released from the Bothrops jararaca plasma by chymotrypsin, an indirect indication of the presence of angiotensinogen in the plasma of this reptile was obtained."}
{"id": "PMID:205120", "title": "Cellular control of collagen breakdown in rheumatoid arthritis.", "content": "Remodelling of connective tissue and its destruction in rheumatoid arthritis is related to collagenolysis. Study of collagenase released by rheumatoid synovial cels has indicated that the enzyme is released as latent form from adherent synovial cells in culture. As a latent enzyme it is protected from complexing with alpha2 macroglobulin, the principal proteinase inhibitor. Activation in vivo is very likely caused by proteases which destroy or complex with a portion of collagenase responsible for its latency. Recent data suggest that the latent collagenase is an enzyme-inhibitor complex and not a true zymogen.", "contents": "Cellular control of collagen breakdown in rheumatoid arthritis. Remodelling of connective tissue and its destruction in rheumatoid arthritis is related to collagenolysis. Study of collagenase released by rheumatoid synovial cels has indicated that the enzyme is released as latent form from adherent synovial cells in culture. As a latent enzyme it is protected from complexing with alpha2 macroglobulin, the principal proteinase inhibitor. Activation in vivo is very likely caused by proteases which destroy or complex with a portion of collagenase responsible for its latency. Recent data suggest that the latent collagenase is an enzyme-inhibitor complex and not a true zymogen."}
{"id": "PMID:205123", "title": "Percutaneous needle biopsy of bone in the cancer patient.", "content": "Needle biopsy of skeletal lesions is easily accomplished by the percutaneous technique. Although this approach has been utilized for many years, the frequency has definitely increased of the 91 cases performed at M. D. Anderson Hospital and Tumor Institute from September 1976 to September 1977, adequate material was obtained in 92.3% of the patients, and the diagnosis was established accurately in 83.5% of the cases. No complications were encountered. The technique, indications, and contraindications are discussed and illustrated with representative cases. The contribution of this technique to the management of patients with malignant disease is significant. The benefits include rapid and accurate establishment of a tissue diagnosis, avoidance of a surgical procedure with its associated risks and cost, and simplicity and safety of the procedure facilitating its repetition if needed.", "contents": "Percutaneous needle biopsy of bone in the cancer patient. Needle biopsy of skeletal lesions is easily accomplished by the percutaneous technique. Although this approach has been utilized for many years, the frequency has definitely increased of the 91 cases performed at M. D. Anderson Hospital and Tumor Institute from September 1976 to September 1977, adequate material was obtained in 92.3% of the patients, and the diagnosis was established accurately in 83.5% of the cases. No complications were encountered. The technique, indications, and contraindications are discussed and illustrated with representative cases. The contribution of this technique to the management of patients with malignant disease is significant. The benefits include rapid and accurate establishment of a tissue diagnosis, avoidance of a surgical procedure with its associated risks and cost, and simplicity and safety of the procedure facilitating its repetition if needed."}
{"id": "PMID:205124", "title": "Sonography of the common bile duct: value of the right anterior oblique view.", "content": "The common hepatic and proximal common bile ducts (common duct) lie anteriorly and generally to the right of the portal vein in the porta hepatis. This constant anatomic relationship can be used to demonstrate the common duct and to differentiate it from the portal vein by gray scale ultrasonography. The patient is scanned longitudinally from the right anterior abdominal wall with the ultrasound beam directed posteromedially until two tubular structures are demonstrated in the porta hepatis. The more anterior tubular structure in this projection is the common duct. If the common duct is less than 3 mm in diameter, it may not be clearly delineated. In these cases the absence of common duct dilatation can be inferred. The usefulness of this view for detecting common duct dilatation was evaluated in a series of 101 consecutive cases proven by surgery, autopsy, or cholangiography. The overall accuracy was 96% (four false negative studies; no false positives). We conclude that sonography should be the imaging procedure of choice for suspected extrahepatic biliary obstruction if the serum bilirubin level precludes intravenous cholangiography.", "contents": "Sonography of the common bile duct: value of the right anterior oblique view. The common hepatic and proximal common bile ducts (common duct) lie anteriorly and generally to the right of the portal vein in the porta hepatis. This constant anatomic relationship can be used to demonstrate the common duct and to differentiate it from the portal vein by gray scale ultrasonography. The patient is scanned longitudinally from the right anterior abdominal wall with the ultrasound beam directed posteromedially until two tubular structures are demonstrated in the porta hepatis. The more anterior tubular structure in this projection is the common duct. If the common duct is less than 3 mm in diameter, it may not be clearly delineated. In these cases the absence of common duct dilatation can be inferred. The usefulness of this view for detecting common duct dilatation was evaluated in a series of 101 consecutive cases proven by surgery, autopsy, or cholangiography. The overall accuracy was 96% (four false negative studies; no false positives). We conclude that sonography should be the imaging procedure of choice for suspected extrahepatic biliary obstruction if the serum bilirubin level precludes intravenous cholangiography."}
{"id": "PMID:205125", "title": "Diagnostic accuracy of CT in circumscript liver disease.", "content": "To evaluate the accuracy of CT in diagnosing circumscript liver disease, CT findings in 105 patients were compared to the results of invasive diagnostic procedures (laparoscopy, laparotomy, and autopsy). In all patients at least one of these procedures was performed in addition to CT. CT proved to be a valuable noninvasive method in detecting and differentiating circumscript liver lesions such us metastases, primary liver tumors, solitary cysts and polycystic disease, abscesses, and echinococciasis. The 10% rate of false positive and false negative diagnoses indicates the limitations of the method.", "contents": "Diagnostic accuracy of CT in circumscript liver disease. To evaluate the accuracy of CT in diagnosing circumscript liver disease, CT findings in 105 patients were compared to the results of invasive diagnostic procedures (laparoscopy, laparotomy, and autopsy). In all patients at least one of these procedures was performed in addition to CT. CT proved to be a valuable noninvasive method in detecting and differentiating circumscript liver lesions such us metastases, primary liver tumors, solitary cysts and polycystic disease, abscesses, and echinococciasis. The 10% rate of false positive and false negative diagnoses indicates the limitations of the method."}
{"id": "PMID:205127", "title": "[Prostaglandins and bronchial asthma (author's transl)].", "content": "Prostaglandins (PG) show different effects on the bronchomotoric excitability depending on the fact to which group they certain. The best investigated PG are PGE1, PGE2 (bronchodilators) and PGF2a (bronchoconstrictor). It is possible that PG play a certain role in the pathogenesis of bronchial asthma. Among other hypotheses, the influence upon adenylate cyclase - cAMP systems (without affecting the adrenoreceptors) is evident. Probably, PG exert a regulatory function on bronchial tone. The pathogenetic imporatnce of PG metabolites for bronchial asthma is discussed. A therapeutical influence upon bronchial asthma is theoretically possible on four ways: by 1) stimulation of partial endogenous synthesis of PGE, 2) inhibition of the biotransformation of PGE, 3) exogenous application of PGE, i.e. development of PGE derivatives indifferent to bronchial mucosa, stable in solution and relatively resistant to biotransformation and 4) inhibition of biosynthesis of PGF2a. The development of synthetic PGE1 derivatives (15-methyl-11-desoxy-PGE1) appears to be of future importance. Summarizing we can say that, at the present stage of development, a directed therapeutic utilization of PG for bronchial asthma seems to be of low probability yet. The problem of aspirin-induced asthma including all its practical consequences is discussed.", "contents": "[Prostaglandins and bronchial asthma (author's transl)]. Prostaglandins (PG) show different effects on the bronchomotoric excitability depending on the fact to which group they certain. The best investigated PG are PGE1, PGE2 (bronchodilators) and PGF2a (bronchoconstrictor). It is possible that PG play a certain role in the pathogenesis of bronchial asthma. Among other hypotheses, the influence upon adenylate cyclase - cAMP systems (without affecting the adrenoreceptors) is evident. Probably, PG exert a regulatory function on bronchial tone. The pathogenetic imporatnce of PG metabolites for bronchial asthma is discussed. A therapeutical influence upon bronchial asthma is theoretically possible on four ways: by 1) stimulation of partial endogenous synthesis of PGE, 2) inhibition of the biotransformation of PGE, 3) exogenous application of PGE, i.e. development of PGE derivatives indifferent to bronchial mucosa, stable in solution and relatively resistant to biotransformation and 4) inhibition of biosynthesis of PGF2a. The development of synthetic PGE1 derivatives (15-methyl-11-desoxy-PGE1) appears to be of future importance. Summarizing we can say that, at the present stage of development, a directed therapeutic utilization of PG for bronchial asthma seems to be of low probability yet. The problem of aspirin-induced asthma including all its practical consequences is discussed."}
{"id": "PMID:205128", "title": "Synergistic effects of dietary carbohydrate and cholesterol on serum lipids and lipoproteins in squirrel and spider monkeys.", "content": "Serum lipid and lipoprotein responses to diets with a high level of simple carbohydrate (69% w/w sucrose) and a low level of saturated fat (5% w/w butter-coconut oil, polyunsaturated/saturated fatty acid ratio 0.03) containing 0, 0.1, and 1.0 mg/kcal added cholesterol was studied in five squirrel (Saimiri sciurea) monkeys. Variations in response produced by altering the nature of dietary carbohydrate (sucrose versus dextrin) and the fat (polyunsaturated/saturated fatty acid ratio, 0.03 versus 1.5) in the above diets were studied in three groups (five per group) of spider monkeys (Ateles sp.). In the absence of exogenous cholesterol, feeding a sucrose-saturated fat diet for 6 weeks produced a consistent increase in serum cholesterol in both species and an increase in serum triglycerides only in squirrel monkeys. Exogenous cholesterol had a remarkable synergistic effect on the high carbohydrate diet in increasing the serum cholesterol and had a suppressing effect on serum triglycerides in both species. Polyunsaturated fat reduced the hypercholesterolemic effect of sucrose with or without exogenous cholesterol. Dextrin diets resulted in lower serum cholesterol responses than sucrose diets when the diets contained 0 or 0.1 mg/kcal added cholesterol. Serum cholesterol response was reflected in beta- and alpha-lipoproteins. These results emphasize the varied response of serum lipids and lipoproteins to dietary changes in carbohydrate, fat, and cholesterol that might have a bearing on experimental atherosclerosis.", "contents": "Synergistic effects of dietary carbohydrate and cholesterol on serum lipids and lipoproteins in squirrel and spider monkeys. Serum lipid and lipoprotein responses to diets with a high level of simple carbohydrate (69% w/w sucrose) and a low level of saturated fat (5% w/w butter-coconut oil, polyunsaturated/saturated fatty acid ratio 0.03) containing 0, 0.1, and 1.0 mg/kcal added cholesterol was studied in five squirrel (Saimiri sciurea) monkeys. Variations in response produced by altering the nature of dietary carbohydrate (sucrose versus dextrin) and the fat (polyunsaturated/saturated fatty acid ratio, 0.03 versus 1.5) in the above diets were studied in three groups (five per group) of spider monkeys (Ateles sp.). In the absence of exogenous cholesterol, feeding a sucrose-saturated fat diet for 6 weeks produced a consistent increase in serum cholesterol in both species and an increase in serum triglycerides only in squirrel monkeys. Exogenous cholesterol had a remarkable synergistic effect on the high carbohydrate diet in increasing the serum cholesterol and had a suppressing effect on serum triglycerides in both species. Polyunsaturated fat reduced the hypercholesterolemic effect of sucrose with or without exogenous cholesterol. Dextrin diets resulted in lower serum cholesterol responses than sucrose diets when the diets contained 0 or 0.1 mg/kcal added cholesterol. Serum cholesterol response was reflected in beta- and alpha-lipoproteins. These results emphasize the varied response of serum lipids and lipoproteins to dietary changes in carbohydrate, fat, and cholesterol that might have a bearing on experimental atherosclerosis."}
{"id": "PMID:205129", "title": "Extrauterine mesodermal (m\u00fcllerian) adenosarcoma: a clinicopathologic analysis of five cases.", "content": "Five extrauterine examples (three pelvic and two ovarian) of a distinctive mesodermal (m\u00fcllerian) mixed tumor previously described to occur in the uterus and designated m\u00fcllerian adenosarcoma are reported. The tumors were diagnosed during the fifth to eight decades of life. They usually formed very large, partly cystic masses, which had occasionally spread to adjacent organs by the time of operation. On microscopic examination the tumors consisted of benign-appearing neoplastic glands lying in a sarcomatous stroma. The glands were lined by a variety of m\u00fcllerian epithelial cell types, and the stromal element resembled endometrial stromal sarcoma. Three patients had malignant courses manifested by intrabdominal recurrence, distant metastases, or both. This tumor should be clearly distinguished from the more common forms of mesodermal (m\u00fcllerian) mixed tumor in which the epithilial as well as the stromal component is malignant and the prognosis is much more grave.", "contents": "Extrauterine mesodermal (m\u00fcllerian) adenosarcoma: a clinicopathologic analysis of five cases. Five extrauterine examples (three pelvic and two ovarian) of a distinctive mesodermal (m\u00fcllerian) mixed tumor previously described to occur in the uterus and designated m\u00fcllerian adenosarcoma are reported. The tumors were diagnosed during the fifth to eight decades of life. They usually formed very large, partly cystic masses, which had occasionally spread to adjacent organs by the time of operation. On microscopic examination the tumors consisted of benign-appearing neoplastic glands lying in a sarcomatous stroma. The glands were lined by a variety of m\u00fcllerian epithelial cell types, and the stromal element resembled endometrial stromal sarcoma. Three patients had malignant courses manifested by intrabdominal recurrence, distant metastases, or both. This tumor should be clearly distinguished from the more common forms of mesodermal (m\u00fcllerian) mixed tumor in which the epithilial as well as the stromal component is malignant and the prognosis is much more grave."}
{"id": "PMID:205130", "title": "Immunoglobulin inclusions in non-Hodgkin's lymphomas.", "content": "The occurrence and characteristics of intracellular immunoglobulin inclusions in non-Hodgkin's lymphomas are described. Lymphoma cells from three patients with immunoblastic sarcoma contained classic cytoplasmic, periodic acid-Schiff (PAS)-positive Russell bodies. Immunoperoxidase staining revealed monoclonal IgG (k) in two cases and a polyclonal pattern in the third case, where the tumor evolved from a reactive lesion. Unusual cytoplasmic inclusions were observed in the neoplastic cells of two patients with follicular center cell lymphoma. In one case large globular structures lacking a distinct limiting membrane were seen, while the cells of the other patient contained \"signet-ring-like\" vacuoles filled with microvesicles. Both were PAS-negative and showed monoclonal immunglobulin staining. In two other cases PAS-positive intranuclear inclusions consisting of monoclonal immunoglobulin IgM(k) could be demonstrated. The possible significance of these findings in B-lymphocyte derived neoplasms is discussed.", "contents": "Immunoglobulin inclusions in non-Hodgkin's lymphomas. The occurrence and characteristics of intracellular immunoglobulin inclusions in non-Hodgkin's lymphomas are described. Lymphoma cells from three patients with immunoblastic sarcoma contained classic cytoplasmic, periodic acid-Schiff (PAS)-positive Russell bodies. Immunoperoxidase staining revealed monoclonal IgG (k) in two cases and a polyclonal pattern in the third case, where the tumor evolved from a reactive lesion. Unusual cytoplasmic inclusions were observed in the neoplastic cells of two patients with follicular center cell lymphoma. In one case large globular structures lacking a distinct limiting membrane were seen, while the cells of the other patient contained \"signet-ring-like\" vacuoles filled with microvesicles. Both were PAS-negative and showed monoclonal immunglobulin staining. In two other cases PAS-positive intranuclear inclusions consisting of monoclonal immunoglobulin IgM(k) could be demonstrated. The possible significance of these findings in B-lymphocyte derived neoplasms is discussed."}
{"id": "PMID:205132", "title": "Poland syndrome in British Columbia: incidence and reproductive experience of affected persons.", "content": "Patients with Poland syndrome were ascertained through the British Columbia Health Surveillance Registry, through hospital records, and through practicing plastic and orthopedic surgeons. Of 44 patients who were ascertained, 28 had family histories taken and were examined. Physical findings were: absence of the sternal head of the pectoralis major in all patients, symbrachydactyly in most patients, and infrequent other associations such as ipsilateral undescended testis, M\u00f6bius syndrome, clubfoot, and submucous cleft palate. Family histories were \"negative\" in all cases. The 8 affected adults had 24 reportedly normal children. Mean paternal age was significantly higher than the paternal age in the population. The incidence was 1/32,000 livebirths in British Columbia. It was concluded that in the British Columbia population the syndrome is usually a sporadic event.", "contents": "Poland syndrome in British Columbia: incidence and reproductive experience of affected persons. Patients with Poland syndrome were ascertained through the British Columbia Health Surveillance Registry, through hospital records, and through practicing plastic and orthopedic surgeons. Of 44 patients who were ascertained, 28 had family histories taken and were examined. Physical findings were: absence of the sternal head of the pectoralis major in all patients, symbrachydactyly in most patients, and infrequent other associations such as ipsilateral undescended testis, M\u00f6bius syndrome, clubfoot, and submucous cleft palate. Family histories were \"negative\" in all cases. The 8 affected adults had 24 reportedly normal children. Mean paternal age was significantly higher than the paternal age in the population. The incidence was 1/32,000 livebirths in British Columbia. It was concluded that in the British Columbia population the syndrome is usually a sporadic event."}
{"id": "PMID:205134", "title": "Gestational trophoblastic neoplasms: morphologic correlates of therapeutic response.", "content": "GTN were evaluated histologically in reference to biologic behavior and response to chemotherapy. GTN requiring more intensive, multiple drug chemotherapy usually exhibited increased mitotic activity, nuclear atypias, compact growth of cytotrophoblast, and little maturation, as compared to lesions that responded more favorably. Fibrinoid at the interface of tumor and host tissues was associated with a favorable response to drug therapy. Patients requiring more intensive chemotherapy were more likely to present with distant metastases and high levels of hCG prior to treatment and to reach remission only after many courses of treatment. The clinical and morphologic features of fatal cases suggest that these represented the extreme of a biologic continuum, with collapse of defense mechanisms despite chemotherapy. The early recognition by the pathologist of those lesions that may be resistant to chemotherapy is important to the clinician in selection of an optimal treatment protocol.", "contents": "Gestational trophoblastic neoplasms: morphologic correlates of therapeutic response. GTN were evaluated histologically in reference to biologic behavior and response to chemotherapy. GTN requiring more intensive, multiple drug chemotherapy usually exhibited increased mitotic activity, nuclear atypias, compact growth of cytotrophoblast, and little maturation, as compared to lesions that responded more favorably. Fibrinoid at the interface of tumor and host tissues was associated with a favorable response to drug therapy. Patients requiring more intensive chemotherapy were more likely to present with distant metastases and high levels of hCG prior to treatment and to reach remission only after many courses of treatment. The clinical and morphologic features of fatal cases suggest that these represented the extreme of a biologic continuum, with collapse of defense mechanisms despite chemotherapy. The early recognition by the pathologist of those lesions that may be resistant to chemotherapy is important to the clinician in selection of an optimal treatment protocol."}
{"id": "PMID:205131", "title": "Current concepts in the management of small cell carcinoma of the lung.", "content": "Small cell carcinoma of the lung should be viewed as a widely disseminated disease in all patients. Therefore, systemic treatment with intensive combination chemotherapy should now be considered as the primary and initial treatment modality. The role of radiation therapy for local or involved-field needs to be re-examined to determine if such localized therapy following intensive combination chemotherapy offers any benefits in response rate or survival duration. The role of immunotherapy is not established, and further controlled studies are necessary to define such a role, if any does exist. Prophylactic whole brain irradiation may be useful to avoid neurologic complications, however, it does not appear to improve response rate or survival duration. A randomized study needs to be done to see whether prophylactic whole brain irradiation following complete remission alters the occurrence rate of brain metastases. Response rates up to 100% and disease free survivals greater than one year have been reported. Therefore, a realistic potential for cure exists for some patients with this particular type of lung cancer.", "contents": "Current concepts in the management of small cell carcinoma of the lung. Small cell carcinoma of the lung should be viewed as a widely disseminated disease in all patients. Therefore, systemic treatment with intensive combination chemotherapy should now be considered as the primary and initial treatment modality. The role of radiation therapy for local or involved-field needs to be re-examined to determine if such localized therapy following intensive combination chemotherapy offers any benefits in response rate or survival duration. The role of immunotherapy is not established, and further controlled studies are necessary to define such a role, if any does exist. Prophylactic whole brain irradiation may be useful to avoid neurologic complications, however, it does not appear to improve response rate or survival duration. A randomized study needs to be done to see whether prophylactic whole brain irradiation following complete remission alters the occurrence rate of brain metastases. Response rates up to 100% and disease free survivals greater than one year have been reported. Therefore, a realistic potential for cure exists for some patients with this particular type of lung cancer."}
{"id": "PMID:205135", "title": "Estimation of age from the pubic symphysis by means of multiple regression analysis.", "content": "This study has been carried out to assess the age from the pubic symphysial surface employing a multiple regression analysis and a quantification theory model I analysis. Using partial regression coefficients and/or normalized scores obtained from the analyses, ages of skeletal remains can be quantitatively estimated with a fairly high reliability. The use of this method is, however, limited to the samples between 18 and 38 years of age, because age changes in the symphysial surface show large variations after about 40 years. The reliability of this method was also examined.", "contents": "Estimation of age from the pubic symphysis by means of multiple regression analysis. This study has been carried out to assess the age from the pubic symphysial surface employing a multiple regression analysis and a quantification theory model I analysis. Using partial regression coefficients and/or normalized scores obtained from the analyses, ages of skeletal remains can be quantitatively estimated with a fairly high reliability. The use of this method is, however, limited to the samples between 18 and 38 years of age, because age changes in the symphysial surface show large variations after about 40 years. The reliability of this method was also examined."}
{"id": "PMID:205136", "title": "Glomangioma of the lung.", "content": "An unusual pulmonary tumor was identified on the basis of light and electron microscopic findings as glomangioma. The ultrastructural findings of intracytoplasmic fibrils with dense bodies, electron-dense plaques, pinocytotic vesicles, and basement membranes are consistent with smooth muscle origin. The differential diagnosis between our tumor and other unusual tumors is discussed. The occurrence of a glomangioma in the lung may indicate the existence of pulmonary glomera.", "contents": "Glomangioma of the lung. An unusual pulmonary tumor was identified on the basis of light and electron microscopic findings as glomangioma. The ultrastructural findings of intracytoplasmic fibrils with dense bodies, electron-dense plaques, pinocytotic vesicles, and basement membranes are consistent with smooth muscle origin. The differential diagnosis between our tumor and other unusual tumors is discussed. The occurrence of a glomangioma in the lung may indicate the existence of pulmonary glomera."}
{"id": "PMID:205137", "title": "Relationship of necrosis and tumor border to lymph node metastases and 10-year survival in carcinoma of the breast.", "content": "The pathologic findings of 330 patients with invasive carcinoma of the breast who were followed for 10 years after radical mastectomy was reviewed. The presence or absence of necrosis and the character of the border of the tumor were two factors which were observable in all cases. Necrosis in the carcinoma was associated with a higher mortality rate, a higher incidence of axillary node metastases, and a higher mortality rate in patients with axillary node metastases than were primary carcinomas without necrosis. Tumors with necrosis and a root border showed significantly more aggressive behavior than did those tumors with a rounded border and no necrosis.", "contents": "Relationship of necrosis and tumor border to lymph node metastases and 10-year survival in carcinoma of the breast. The pathologic findings of 330 patients with invasive carcinoma of the breast who were followed for 10 years after radical mastectomy was reviewed. The presence or absence of necrosis and the character of the border of the tumor were two factors which were observable in all cases. Necrosis in the carcinoma was associated with a higher mortality rate, a higher incidence of axillary node metastases, and a higher mortality rate in patients with axillary node metastases than were primary carcinomas without necrosis. Tumors with necrosis and a root border showed significantly more aggressive behavior than did those tumors with a rounded border and no necrosis."}
{"id": "PMID:205141", "title": "[Opiate receptors and endorphines (author's transl)].", "content": "Recent progress in narcotic drug research is briefly reviewed. Several investigators were able, independently to identify stereospecific opiate receptors, which mediate the specific effects of narcotic analgesics. A possible physiological importance of opiate receptors is likely, since endogenous ligands could be detected. Especially from brain and from pituitary glands of several species, quite a number of peptides with morphine-like effects could be isolated. The chemical structure of some of these endorphines could be analyzed. Endorphines are suggested to be involved in pain perception, electroanalgesia, acupuncture analgesia, psychiatric disorders, synthesis and release of pituitary hormones.", "contents": "[Opiate receptors and endorphines (author's transl)]. Recent progress in narcotic drug research is briefly reviewed. Several investigators were able, independently to identify stereospecific opiate receptors, which mediate the specific effects of narcotic analgesics. A possible physiological importance of opiate receptors is likely, since endogenous ligands could be detected. Especially from brain and from pituitary glands of several species, quite a number of peptides with morphine-like effects could be isolated. The chemical structure of some of these endorphines could be analyzed. Endorphines are suggested to be involved in pain perception, electroanalgesia, acupuncture analgesia, psychiatric disorders, synthesis and release of pituitary hormones."}
{"id": "PMID:205142", "title": "The freeze-fracture study of alveolar type II cells and alveolar content in fetal rabbit lung.", "content": "Freeze-fracture replication technique was utilized to study the morphology of type II alveolar epithelial cells and alveolar contents in the late gestation of rabbit fetuses. It was shown that the lamellar inclusion bodies of type II cells were enveloped by the usual type of unit membrane with membrane-associated particles of 15 nm diameter. The interior of the inclusion bodies was composed of multiple stacks and/or whorls of membranes which were devoid of membrane-associated particles. Small vesicles within the inclusion were found more frequently with this technique than in chemically fixed thin-sectioned preparations. The intra-alveolar contents were comprised of two components; sperical bodies, which were identical to the internal contents of the lamellar bodies of type II cells, and tubular elements. These tubules most often appeared rectangular on cross-fractured faces. Triangular hexagonal fracture faces were also noted. The tubules were seen to rest on the surfaces of the spherical components. Our observations suggest that the tubular element of alveolar contents is formed through the interaction between the discharged lamellar body content and the alveolar fluid, and further suggest that at least the major constituent of type II cell lamellar bodies is lipid not bound to protein. Three new observations were made in this study; the absence of membrane-associated particles on the interior of the lamellae of the inclusions, the cross-fractured profiles of tubular elements of the alveolar contents, and the occasional multicompartmental nature of type II cell inclusions.", "contents": "The freeze-fracture study of alveolar type II cells and alveolar content in fetal rabbit lung. Freeze-fracture replication technique was utilized to study the morphology of type II alveolar epithelial cells and alveolar contents in the late gestation of rabbit fetuses. It was shown that the lamellar inclusion bodies of type II cells were enveloped by the usual type of unit membrane with membrane-associated particles of 15 nm diameter. The interior of the inclusion bodies was composed of multiple stacks and/or whorls of membranes which were devoid of membrane-associated particles. Small vesicles within the inclusion were found more frequently with this technique than in chemically fixed thin-sectioned preparations. The intra-alveolar contents were comprised of two components; sperical bodies, which were identical to the internal contents of the lamellar bodies of type II cells, and tubular elements. These tubules most often appeared rectangular on cross-fractured faces. Triangular hexagonal fracture faces were also noted. The tubules were seen to rest on the surfaces of the spherical components. Our observations suggest that the tubular element of alveolar contents is formed through the interaction between the discharged lamellar body content and the alveolar fluid, and further suggest that at least the major constituent of type II cell lamellar bodies is lipid not bound to protein. Three new observations were made in this study; the absence of membrane-associated particles on the interior of the lamellae of the inclusions, the cross-fractured profiles of tubular elements of the alveolar contents, and the occasional multicompartmental nature of type II cell inclusions."}
{"id": "PMID:205145", "title": "Induction of a cell membrane antigen by equine infectious anemia virus.", "content": "Equine fibroblasts persistently infected with equine infectious anemia virus acquire a new cell membrane antigen demonstrable by indirect radioimmunoassay, using infected horse serum as an antibody source.", "contents": "Induction of a cell membrane antigen by equine infectious anemia virus. Equine fibroblasts persistently infected with equine infectious anemia virus acquire a new cell membrane antigen demonstrable by indirect radioimmunoassay, using infected horse serum as an antibody source."}
{"id": "PMID:205146", "title": "Burro aortic collagen: platelet aggregating activity and ultrastructural changes induced by plasma.", "content": "A fibrillar collagen molecule was extracted from the upper thoracic aorta of an old burro (Equus asinus). Presence of the collagen in the extract was determined by amino acid analysis, scanning and transmission electron microscopy, incubation with collagenase, and assays of its platelet-aggregating capacity by \"aggregometry\". Based on the amino acid rations of proline/hydroxyproline and lysine/hydroxylysine, the collagenous protein most nearly resembles type I of 4 main published types of collagen. Quantitative assays of the collagen as a mediator of platelet aggregation showed human platelets more sensitive and sheep platelets slightly less sensitive than burro platelets. Incubation with collagenase abolished platelet aggregation  capacity and converted the fibrillar collagen to a gel-like mass. Incubation with galactose oxidase neither lessened nor intensified the collagen-mediated platelet aggregation. Incubation with burro plasma decreased platelet aggregating activity and changed the collagen ultrastructure (demonstrated with scanning electron microscopic imaging). The significance of a naturally occurring plasma (protein) factor(s) which may have a regulatory role in reducing the chemical activity of the fibrillar collagen molecule with platelets is also discussed.", "contents": "Burro aortic collagen: platelet aggregating activity and ultrastructural changes induced by plasma. A fibrillar collagen molecule was extracted from the upper thoracic aorta of an old burro (Equus asinus). Presence of the collagen in the extract was determined by amino acid analysis, scanning and transmission electron microscopy, incubation with collagenase, and assays of its platelet-aggregating capacity by \"aggregometry\". Based on the amino acid rations of proline/hydroxyproline and lysine/hydroxylysine, the collagenous protein most nearly resembles type I of 4 main published types of collagen. Quantitative assays of the collagen as a mediator of platelet aggregation showed human platelets more sensitive and sheep platelets slightly less sensitive than burro platelets. Incubation with collagenase abolished platelet aggregation  capacity and converted the fibrillar collagen to a gel-like mass. Incubation with galactose oxidase neither lessened nor intensified the collagen-mediated platelet aggregation. Incubation with burro plasma decreased platelet aggregating activity and changed the collagen ultrastructure (demonstrated with scanning electron microscopic imaging). The significance of a naturally occurring plasma (protein) factor(s) which may have a regulatory role in reducing the chemical activity of the fibrillar collagen molecule with platelets is also discussed."}
{"id": "PMID:205147", "title": "An immunofluorescence diagnostic test for feline viral rhinotracheitis.", "content": "Hyperimmune serum against feline viral rhinotracheitis was produced in a goat and conjugated with a fluorescent dye. Cell cultures infected with rhinotracheitis virus had positive immunofluorescence. Cell cultures infected with other feline viruses and herpesviruses of other species did not fluoresce. In cats experimentally infected with rhinotracheitis virus, the virus was isolated from nasal and conjunctival swabs 1 to 9 days after inoculation. Nasal smears stained with the conjugated antiserum fluoresced 1 to 9 days after inoculation when clinical disease was most apparent. Conjunctival smears had positive immunofluorescence 1 to 6 days, but not 9 days, after inoculation. On postinoculation day 23, rhinotracheitis virus was not isolated from nasal or conjunctival swabs and nasal and conjunctival smears did not fluoresce. Rhinotracheitis virus or feline calicivirus was isolated from naturally infected cats with upper respiratory tract disease. Nasal and conjunctival smears from rhinotracheitis virus-infected cats had positive immunofluorescence in all cast showing clinical illness. Smears from 1 clinically normal cat from which rhinotracheitis virus was isolated did not fluoresce. Nasal and conjunctival smears from calicivirus-infected cats did not fluoresce.", "contents": "An immunofluorescence diagnostic test for feline viral rhinotracheitis. Hyperimmune serum against feline viral rhinotracheitis was produced in a goat and conjugated with a fluorescent dye. Cell cultures infected with rhinotracheitis virus had positive immunofluorescence. Cell cultures infected with other feline viruses and herpesviruses of other species did not fluoresce. In cats experimentally infected with rhinotracheitis virus, the virus was isolated from nasal and conjunctival swabs 1 to 9 days after inoculation. Nasal smears stained with the conjugated antiserum fluoresced 1 to 9 days after inoculation when clinical disease was most apparent. Conjunctival smears had positive immunofluorescence 1 to 6 days, but not 9 days, after inoculation. On postinoculation day 23, rhinotracheitis virus was not isolated from nasal or conjunctival swabs and nasal and conjunctival smears did not fluoresce. Rhinotracheitis virus or feline calicivirus was isolated from naturally infected cats with upper respiratory tract disease. Nasal and conjunctival smears from rhinotracheitis virus-infected cats had positive immunofluorescence in all cast showing clinical illness. Smears from 1 clinically normal cat from which rhinotracheitis virus was isolated did not fluoresce. Nasal and conjunctival smears from calicivirus-infected cats did not fluoresce."}
{"id": "PMID:205148", "title": "Pancreas-passaged avian encephalomyelitis virus and its immunogenicity.", "content": "A serial 34-chicken pancreas passage of avian encephalomyelitis virus by oral administration was successful. Oral inoculation test with 4 passaged viruses showed rapid infection of the duodenal wall and unchangeable infection of pancreas diminishing the viral invasiveness to other organs. The passaged virus caused neither detectable viremia nor clinical avian encephalomyelitis signs and produced neutralizing antibody of high titers.", "contents": "Pancreas-passaged avian encephalomyelitis virus and its immunogenicity. A serial 34-chicken pancreas passage of avian encephalomyelitis virus by oral administration was successful. Oral inoculation test with 4 passaged viruses showed rapid infection of the duodenal wall and unchangeable infection of pancreas diminishing the viral invasiveness to other organs. The passaged virus caused neither detectable viremia nor clinical avian encephalomyelitis signs and produced neutralizing antibody of high titers."}
{"id": "PMID:205149", "title": "Diagnosis of avian viral diseass by electron microscopy.", "content": "Clinical material from avian species was examined directly by electron microscopy for the presence of viruses. Mycoplasma-like and coronavirus-like particles were found in chicken feces. These particles did not appear to be associated with disease and were not propagated in the laboratory. Infectious bursal disease virus was readily detected in impression smears of bursas from experimentally infected birds. Poxviruses were demonstrated in smears made from canarypox lesions. Difficulty in distinguishing intact particles of Newcastle disease virus from mycoplasmas and orthomyxoviruses was resolved by treating viral preparations with deoxycholate. After treatment, Newcastle disease virus was lysed, rendering the nucleocapsid visible, whereas influenza virus was mainly unaffected. Viral particles that were recognized only with difficulty by direct elecron microscopic examination were more easily identified using immunoelectron microscopy.", "contents": "Diagnosis of avian viral diseass by electron microscopy. Clinical material from avian species was examined directly by electron microscopy for the presence of viruses. Mycoplasma-like and coronavirus-like particles were found in chicken feces. These particles did not appear to be associated with disease and were not propagated in the laboratory. Infectious bursal disease virus was readily detected in impression smears of bursas from experimentally infected birds. Poxviruses were demonstrated in smears made from canarypox lesions. Difficulty in distinguishing intact particles of Newcastle disease virus from mycoplasmas and orthomyxoviruses was resolved by treating viral preparations with deoxycholate. After treatment, Newcastle disease virus was lysed, rendering the nucleocapsid visible, whereas influenza virus was mainly unaffected. Viral particles that were recognized only with difficulty by direct elecron microscopic examination were more easily identified using immunoelectron microscopy."}
{"id": "PMID:205150", "title": "Parainfluenza-3 virus exposure of beef heifers prior to natural breeding.", "content": "Ninety-six Hereford heifers (approximately 7 months of age) were randomly divided into 2 equal groups and housed 1.6 km apart (with 2 replications in time, 1 year apart). At 15 months of age, 1 group/replicate was inoculated with parainfluenza-3 virus, and the other group was given virus-free spent culture medium. Twenty-four hours later, 2 virgin bulls (2 years old) were placed with each group (24 cows) for natural breeding. Viral inoculation caused a twofold increase in parainfluenza-3 titer and a 0.3 C body temperature increase. There was no effect recognized from the virus on natural breeding efficiency.", "contents": "Parainfluenza-3 virus exposure of beef heifers prior to natural breeding. Ninety-six Hereford heifers (approximately 7 months of age) were randomly divided into 2 equal groups and housed 1.6 km apart (with 2 replications in time, 1 year apart). At 15 months of age, 1 group/replicate was inoculated with parainfluenza-3 virus, and the other group was given virus-free spent culture medium. Twenty-four hours later, 2 virgin bulls (2 years old) were placed with each group (24 cows) for natural breeding. Viral inoculation caused a twofold increase in parainfluenza-3 titer and a 0.3 C body temperature increase. There was no effect recognized from the virus on natural breeding efficiency."}
{"id": "PMID:205151", "title": "Hand-to-hand transmission of rhinovirus colds.", "content": "Rhinovirus was transmitted from experimentally infected volunteers (donors) to susceptible recipients and the efficiencies of spread by hand-to-hand contact and large- and small-particle aerosols compared. Transmission of infection was very efficient by the hand route: 11 of 15 hand-contact exposures initiated infection, compared with one of 12 large-particle (P less than 0.005) and none of 10 small-particle (P less than 0.005) exposures. Rhinovirus was present in nine of 18 (50%) nasal swab specimens, 28 of 43 (65%) hand rinses, and seven of 18 (39%) saliva specimens of donors; geometric mean titers of positive specimens were 10(1.5), 10(1.4), and 10(1.2) tissue culture infectious dose 50/ml (TCID 50/ml), respectively. Rhinovirus was present in 20 of 43 (46%) recipient hand rinses, with a geometric mean titer of 10(1.4)TCID50/ml. Virus on donors' hands was transferred to recipients' fingers during 20 of 28 (71%) 10-second hand-contact exposures. These findings support the concept that hand contact/self-inoculation may be an important natural route of rhinovirus transmission.", "contents": "Hand-to-hand transmission of rhinovirus colds. Rhinovirus was transmitted from experimentally infected volunteers (donors) to susceptible recipients and the efficiencies of spread by hand-to-hand contact and large- and small-particle aerosols compared. Transmission of infection was very efficient by the hand route: 11 of 15 hand-contact exposures initiated infection, compared with one of 12 large-particle (P less than 0.005) and none of 10 small-particle (P less than 0.005) exposures. Rhinovirus was present in nine of 18 (50%) nasal swab specimens, 28 of 43 (65%) hand rinses, and seven of 18 (39%) saliva specimens of donors; geometric mean titers of positive specimens were 10(1.5), 10(1.4), and 10(1.2) tissue culture infectious dose 50/ml (TCID 50/ml), respectively. Rhinovirus was present in 20 of 43 (46%) recipient hand rinses, with a geometric mean titer of 10(1.4)TCID50/ml. Virus on donors' hands was transferred to recipients' fingers during 20 of 28 (71%) 10-second hand-contact exposures. These findings support the concept that hand contact/self-inoculation may be an important natural route of rhinovirus transmission."}
{"id": "PMID:205153", "title": "Small-cell carcinoma of the lung: therapeutic management.", "content": "Although bronchogenic carcinoma generally remains a tumor resistant to treatment, marked progress in the therapy of the small-cell undifferentiated subtype has occurred in the past 5 years. Many aspects of its growth and metastatic spread are such that it is not satisfactorily treated surgically. However, it is sensitive to both radiation and a variety of chemotherapeutic agents. Use of these agents in combination seems to produce a greater antitumor effect than single drugs. The combination of radiation and chemotherapy results in marked tumor regressions. Untreated, this carcinoma has a very short median survival (2 months). Administration of current \"aggressive\" combination therapy regimens has resulted in median survivals of nearly 1 year with some patients still living 3 years after therapy.", "contents": "Small-cell carcinoma of the lung: therapeutic management. Although bronchogenic carcinoma generally remains a tumor resistant to treatment, marked progress in the therapy of the small-cell undifferentiated subtype has occurred in the past 5 years. Many aspects of its growth and metastatic spread are such that it is not satisfactorily treated surgically. However, it is sensitive to both radiation and a variety of chemotherapeutic agents. Use of these agents in combination seems to produce a greater antitumor effect than single drugs. The combination of radiation and chemotherapy results in marked tumor regressions. Untreated, this carcinoma has a very short median survival (2 months). Administration of current \"aggressive\" combination therapy regimens has resulted in median survivals of nearly 1 year with some patients still living 3 years after therapy."}
{"id": "PMID:205154", "title": "Rubella vaccine. Recommendation of the Public Health Service Advisory Committee on Immunization Practices. Center for Disease Control, U.S. Department of Health, Education, and Welfare; Atlanta, Georgia.", "content": "Rubella infection may be subclinical or overlooked because of the nonspecificity of its most frequent manifestations. Joint involvement is most frequent in women but can occur in men and children. The most serious complication is induction of fetal anomalies in infected pregnant women. This paper reviews the proper use of live rubella virus vaccine for prophylactive immunization and the postexposure treatment with immune serum globulin for modification or suppression of symptoms.", "contents": "Rubella vaccine. Recommendation of the Public Health Service Advisory Committee on Immunization Practices. Center for Disease Control, U.S. Department of Health, Education, and Welfare; Atlanta, Georgia. Rubella infection may be subclinical or overlooked because of the nonspecificity of its most frequent manifestations. Joint involvement is most frequent in women but can occur in men and children. The most serious complication is induction of fetal anomalies in infected pregnant women. This paper reviews the proper use of live rubella virus vaccine for prophylactive immunization and the postexposure treatment with immune serum globulin for modification or suppression of symptoms."}
{"id": "PMID:205163", "title": "Recent progress in the development of radioimmunoassays for human serum lipoproteins.", "content": "A review of radioimmunoassays for measuring human apolipoprotein B (apo B), the A apolipoproteins of high density lipoprotein (apo A-I and apo A-II) and apolipoprotein C-II (apo C-II) in human plasma and in isolated lipoproteins is presented. The sensitivity, specificity and validity of each of these assays is discussed. In normolipidemic subjects the reported serum apo B concentrations ranged between 0.83 +/- 0.16 and 0.92 +/- 0.21 g per l (m +/- SD). Serum apo B concentrations were highest in Type II subjects (Type IIa homozygotes 3.83 +/- 0.43 g per l; Type IIa heterozygotes 2.37 +/- 0.47 g per l) and were less elevated in patients with Type IV and Type V disorders (1.32 +/- 0.21 g per l and 1.26 +/- 0.30 g per l, respectively). Preliminary data on the relationship between plasma apo B and cholesterol, the distribution of apo B amongst the lipoprotein classes and a comparison of the lipoprotein lipid-apo B ratios in the various hyperlipidemic disorders are summarized. In contrast to apo A-II, the immunoreactivity of apo A-I was not fully exposed in whole sera and in isolated lipoproteins. The different methods used to measure the apo A-I immunoreactivity are discussed. In normolipidemic subjects the serum apo A-I concentration in males and females was 1.13 +/- 0.061 and 1.24 +/- 0.068 g per l (m +/- SD), respectively, while the corresponding serum apo A-II values were 0.35 +/- 0.038 g per l and 0.41 +/- 0.046 g per l. In subjects with Tangier's disease, the serum apo A-I and apo A-II concentrations were less than 1 percent and 5 to 7 percent of that found in controls. The serum apo A-I level was also reduced in two subjects with abetalipoproteinemia (0.38 g per l and 0.30 g per l) and Tye II hyperlipoproteinemia (range 0.54 to 0.86 g per l). In normotriglyceridemic subjects and those with Type IIa hyperlipoproteinemia, the total plasma apo C-II concentrations were 0.0497 +/- 0.0040 g per l and 0.0562 +/- 0.0054 g per l (m +/- SE). Plasma apo C-II levels in Type IIb, Type IV and Type V lipoproteinemic subjects were 0.0899 +/- 0.0046, 0.0854 +/- 0.0069 and 0.1328 +/- 0.0021 g per l, respectively and were significantly higher than in the normotriglyceridemic subjects. An analysis of the relationship between the apo C-II content and the lipoprotein lipase activator properties of VLDL isolated from normo- and hypertriglyceridemic plasma samples is presented.", "contents": "Recent progress in the development of radioimmunoassays for human serum lipoproteins. A review of radioimmunoassays for measuring human apolipoprotein B (apo B), the A apolipoproteins of high density lipoprotein (apo A-I and apo A-II) and apolipoprotein C-II (apo C-II) in human plasma and in isolated lipoproteins is presented. The sensitivity, specificity and validity of each of these assays is discussed. In normolipidemic subjects the reported serum apo B concentrations ranged between 0.83 +/- 0.16 and 0.92 +/- 0.21 g per l (m +/- SD). Serum apo B concentrations were highest in Type II subjects (Type IIa homozygotes 3.83 +/- 0.43 g per l; Type IIa heterozygotes 2.37 +/- 0.47 g per l) and were less elevated in patients with Type IV and Type V disorders (1.32 +/- 0.21 g per l and 1.26 +/- 0.30 g per l, respectively). Preliminary data on the relationship between plasma apo B and cholesterol, the distribution of apo B amongst the lipoprotein classes and a comparison of the lipoprotein lipid-apo B ratios in the various hyperlipidemic disorders are summarized. In contrast to apo A-II, the immunoreactivity of apo A-I was not fully exposed in whole sera and in isolated lipoproteins. The different methods used to measure the apo A-I immunoreactivity are discussed. In normolipidemic subjects the serum apo A-I concentration in males and females was 1.13 +/- 0.061 and 1.24 +/- 0.068 g per l (m +/- SD), respectively, while the corresponding serum apo A-II values were 0.35 +/- 0.038 g per l and 0.41 +/- 0.046 g per l. In subjects with Tangier's disease, the serum apo A-I and apo A-II concentrations were less than 1 percent and 5 to 7 percent of that found in controls. The serum apo A-I level was also reduced in two subjects with abetalipoproteinemia (0.38 g per l and 0.30 g per l) and Tye II hyperlipoproteinemia (range 0.54 to 0.86 g per l). In normotriglyceridemic subjects and those with Type IIa hyperlipoproteinemia, the total plasma apo C-II concentrations were 0.0497 +/- 0.0040 g per l and 0.0562 +/- 0.0054 g per l (m +/- SE). Plasma apo C-II levels in Type IIb, Type IV and Type V lipoproteinemic subjects were 0.0899 +/- 0.0046, 0.0854 +/- 0.0069 and 0.1328 +/- 0.0021 g per l, respectively and were significantly higher than in the normotriglyceridemic subjects. An analysis of the relationship between the apo C-II content and the lipoprotein lipase activator properties of VLDL isolated from normo- and hypertriglyceridemic plasma samples is presented."}
{"id": "PMID:205164", "title": "Plasma lipoproteins and coronary heart disease.", "content": "Both plasma low-density (LDL) and high-density lipoproteins (HDL) have been associated with the genesis of cardiovascular disease. Recent studies with cells grown in culture have suggested a regularory role of these lipoproteins in cellular cholesterol metabolism and pointed at abnormalities resulting from deviations of these regulatory processes. The precise relationship between these observations in vitro and the atherogenic process remains open to investigation.", "contents": "Plasma lipoproteins and coronary heart disease. Both plasma low-density (LDL) and high-density lipoproteins (HDL) have been associated with the genesis of cardiovascular disease. Recent studies with cells grown in culture have suggested a regularory role of these lipoproteins in cellular cholesterol metabolism and pointed at abnormalities resulting from deviations of these regulatory processes. The precise relationship between these observations in vitro and the atherogenic process remains open to investigation."}
{"id": "PMID:205170", "title": "[Effect of penicillin on the antigenic properties of serum beta-lipoproteins].", "content": "Peculiar characteristics of the antigenic properties of penicillin compounds with heterological and homological beta-lipoproteids of the blood serum were investigated. The beta-lipoproteids isolated from the blood serum of humans (donors) and rabbits were mixed with potassium benzylpenicillin (10000 and 50000 gamma/ml). Twenty seven rabbits were immunized with such compounds and solutions of beta-lipoproteids without addition of the antibiotic. The antisera obtained from the animals were used in the reaction of precipitation and immunoelectrophoresis, the results of which were densitometrized. Some physico-chemical properties of the preparations, such as pH, electrokinetic features were also studied. It was shown that the immunochemical properties of heterological beta-lipoproteids, i.e. precipitation bands changed due to the effect of penicillin. They differed from the control by compactness and contrastness, their amounts decreased, a separate band not identical to that of the control antigen appeared. A separate or intermediate antigen was found in the experiments with serum exhaustion. The peculiarities of the precipitation reaction were confirmed by the immunoelectrophoregrams. These differences were also registered on the densitograms. The compounds of penicillin with homological beta-lipoproteids of the rabbit blood serum induced formation of specific precipitins in the animals. Some physico-chemical properties of beta-lipoproteids also changed under the effect of penicillin.", "contents": "[Effect of penicillin on the antigenic properties of serum beta-lipoproteins]. Peculiar characteristics of the antigenic properties of penicillin compounds with heterological and homological beta-lipoproteids of the blood serum were investigated. The beta-lipoproteids isolated from the blood serum of humans (donors) and rabbits were mixed with potassium benzylpenicillin (10000 and 50000 gamma/ml). Twenty seven rabbits were immunized with such compounds and solutions of beta-lipoproteids without addition of the antibiotic. The antisera obtained from the animals were used in the reaction of precipitation and immunoelectrophoresis, the results of which were densitometrized. Some physico-chemical properties of the preparations, such as pH, electrokinetic features were also studied. It was shown that the immunochemical properties of heterological beta-lipoproteids, i.e. precipitation bands changed due to the effect of penicillin. They differed from the control by compactness and contrastness, their amounts decreased, a separate band not identical to that of the control antigen appeared. A separate or intermediate antigen was found in the experiments with serum exhaustion. The peculiarities of the precipitation reaction were confirmed by the immunoelectrophoregrams. These differences were also registered on the densitograms. The compounds of penicillin with homological beta-lipoproteids of the rabbit blood serum induced formation of specific precipitins in the animals. Some physico-chemical properties of beta-lipoproteids also changed under the effect of penicillin."}
{"id": "PMID:205172", "title": "Enhanced virus replication in mammalian cells exposed to commercial emulsifiers.", "content": "Mammalian cell cultures were used to show that a variety of commercial emulsifiers are capable of enhancing the sensitivity of these cells to infection with several viruses. Some emulsifiers were not active as enhancers, and those viruses that responded to the enhancing emulsifiers were single-stranded ribonucldic acid viruses. The double-stranded viruses that were tested were nonresponders.", "contents": "Enhanced virus replication in mammalian cells exposed to commercial emulsifiers. Mammalian cell cultures were used to show that a variety of commercial emulsifiers are capable of enhancing the sensitivity of these cells to infection with several viruses. Some emulsifiers were not active as enhancers, and those viruses that responded to the enhancing emulsifiers were single-stranded ribonucldic acid viruses. The double-stranded viruses that were tested were nonresponders."}
{"id": "PMID:205173", "title": "Comparison between adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs.", "content": "Adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs was studied. Both aluminum hydroxide and activated sludge flocs adsorbed greater amounts of poliovirus than rotavirus. Aluminum hydroxide flocs reduced the titer of poliovirus in tap water by 3 log10, but they only reduced the titer of a simian rotovirus (SA-11) in tap water by 1 log10 or less and did not noticeably reduce the number of human rotavirus particles present in a dilute stool suspension. Activated sludge flocs reduced the titer of added poliovirus by 0.7 to 1.8 log10 and reduced the titer of SA-11 by 0.5 log10 or less. These studies indicate that a basic difference in the adsorptive behavior of enteroviruses and rotaviruses exists and that water and wastewater treatment processes that are highly effective in removal of enteroviruses may not be as effective in removing other viral groups such as rotaviruses.", "contents": "Comparison between adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs. Adsorption of poliovirus and rotavirus by aluminum hydroxide and activated sludge flocs was studied. Both aluminum hydroxide and activated sludge flocs adsorbed greater amounts of poliovirus than rotavirus. Aluminum hydroxide flocs reduced the titer of poliovirus in tap water by 3 log10, but they only reduced the titer of a simian rotovirus (SA-11) in tap water by 1 log10 or less and did not noticeably reduce the number of human rotavirus particles present in a dilute stool suspension. Activated sludge flocs reduced the titer of added poliovirus by 0.7 to 1.8 log10 and reduced the titer of SA-11 by 0.5 log10 or less. These studies indicate that a basic difference in the adsorptive behavior of enteroviruses and rotaviruses exists and that water and wastewater treatment processes that are highly effective in removal of enteroviruses may not be as effective in removing other viral groups such as rotaviruses."}
{"id": "PMID:205171", "title": "Thalamic lesions during the development period and their clinical correlation.", "content": "28 autopsy cases were investigated in which the thalamus was impaired in early life, i.e. prenatal, perinatal, and postnatal (under 1 year of age). The thalamus is vulnerable to brain damage in the perinatal and early postnatal period. Lesions in the thalamus are severe in the DM, PL and VPL, and moderate in the VL and pulvinar thalamus. The anterior nuclei and center median show little change. Many of the cases with athetoid movements have complicated thalamic lesions in addition to those of the basal ganglia. In one patient who showed athetosis as a sequela of encephalitis japonica, the VL and PL in the thalamus were involved severely; in contrast the basal ganglia revealed very slight changes.", "contents": "Thalamic lesions during the development period and their clinical correlation. 28 autopsy cases were investigated in which the thalamus was impaired in early life, i.e. prenatal, perinatal, and postnatal (under 1 year of age). The thalamus is vulnerable to brain damage in the perinatal and early postnatal period. Lesions in the thalamus are severe in the DM, PL and VPL, and moderate in the VL and pulvinar thalamus. The anterior nuclei and center median show little change. Many of the cases with athetoid movements have complicated thalamic lesions in addition to those of the basal ganglia. In one patient who showed athetosis as a sequela of encephalitis japonica, the VL and PL in the thalamus were involved severely; in contrast the basal ganglia revealed very slight changes."}
{"id": "PMID:205174", "title": "Observations on toxin and hemagglutinin produced by Clostridium botulinum type C.", "content": "In the culture fluid of a hemagglutinin-positive strain of Clostridium botulinum type C, two toxins of different molecular size, hemagglutinin positive and negative, were separated by sucrose density gradient centrifugation.", "contents": "Observations on toxin and hemagglutinin produced by Clostridium botulinum type C. In the culture fluid of a hemagglutinin-positive strain of Clostridium botulinum type C, two toxins of different molecular size, hemagglutinin positive and negative, were separated by sucrose density gradient centrifugation."}
{"id": "PMID:205175", "title": "Concentration of enteroviruses from large volumes of tap water, treated sewage, and seawater.", "content": "Methods are described for the efficient concentration of an enterovirus from large volumes of tap water, sewage, and seawater. Virus in acidified water (pH 3.5) in the presence of aluminum chloride was adsorbed to a 10-inch (ca. 25.4 cm) fiberglass depth cartridge and a 10-inch pleated epoxy-fiberglass filter in a series at flow rates of up to 37.8 liters (10 gallons) per min. Adsorbed viruses were eluted from the filters with glycine buffer (pH 10.5 to 11.5), and the eluate was reconcentrated by using a combination of aluminum flocculation followed by hydroextraction. With this procedure, poliovirus in large volumes of tap water, seawater, and sewage could be concentrated with an average efficiency of 52, 53, and 50%, respectively. It was demonstrated that this method is capable of detecting surface solid-associated viruses originating from sewage treatment plants. No difference in virus recovery between laboratory batch studies and a set-up with acid-salt injection was found. This unified scheme for the concentration of viruses has many advantages over previously described systems. These include: high operating flow rates, low weight and small size, effectiveness with a variety of waters with widely varying qualities, and filters with a high resistance to clogging.", "contents": "Concentration of enteroviruses from large volumes of tap water, treated sewage, and seawater. Methods are described for the efficient concentration of an enterovirus from large volumes of tap water, sewage, and seawater. Virus in acidified water (pH 3.5) in the presence of aluminum chloride was adsorbed to a 10-inch (ca. 25.4 cm) fiberglass depth cartridge and a 10-inch pleated epoxy-fiberglass filter in a series at flow rates of up to 37.8 liters (10 gallons) per min. Adsorbed viruses were eluted from the filters with glycine buffer (pH 10.5 to 11.5), and the eluate was reconcentrated by using a combination of aluminum flocculation followed by hydroextraction. With this procedure, poliovirus in large volumes of tap water, seawater, and sewage could be concentrated with an average efficiency of 52, 53, and 50%, respectively. It was demonstrated that this method is capable of detecting surface solid-associated viruses originating from sewage treatment plants. No difference in virus recovery between laboratory batch studies and a set-up with acid-salt injection was found. This unified scheme for the concentration of viruses has many advantages over previously described systems. These include: high operating flow rates, low weight and small size, effectiveness with a variety of waters with widely varying qualities, and filters with a high resistance to clogging."}
{"id": "PMID:205178", "title": "The peripheral lymphocyte count as an aid in the clinical staging of lung cancer.", "content": "The association between disease staging and peripheral lymphocyte count (PLC) was studied in 178 patients with histologically verified lung cancer. Mean PLC varied inversely with the stage of disease (p less than .01). The mean values were 2821, 2217, and 1594 for Stages I, II and III respectively. Thoretical normal distributions were generated about the mean peripheral lymphocyte count for each stage. Relative frequencies of lung cancer staging based on the PLC are estimated utilizing these curves.", "contents": "The peripheral lymphocyte count as an aid in the clinical staging of lung cancer. The association between disease staging and peripheral lymphocyte count (PLC) was studied in 178 patients with histologically verified lung cancer. Mean PLC varied inversely with the stage of disease (p less than .01). The mean values were 2821, 2217, and 1594 for Stages I, II and III respectively. Thoretical normal distributions were generated about the mean peripheral lymphocyte count for each stage. Relative frequencies of lung cancer staging based on the PLC are estimated utilizing these curves."}
{"id": "PMID:205179", "title": "Watery diarrhea syndrome. Two unusual cases and further evidence that VIP is a humoral mediator.", "content": "Two unusual cases of the watery diarrhea syndrome are presented. In one patient an adrenal medullary tumor, a pheochromocytoma that produced vasoactive intestinal polypeptide (VIP) was excised with total relief of symptoms. The second patient a 65-year-old man with abrupt onset of massive watery diarrhea that led to acidosis and coma was symptomatically controlled for one year on 10 mg/day of prednisone. Elevated levels of VIP returned to normal after prednisone therapy was started. A benign islet cell tumor not localized by angiography was removed by distal pancreatic resection. Tissue levels of VIP were markedly elevated. VIP is a humoral mediator of the water diarrhea syndrome. Both benign and malignant pancreatic and extrapancreatic tumors may cause the watery diarrhea syndrome. Steroids may cause symptomatic relief of the diarrhea by lowering peptide levels to normal. The term watery diarrhea syndrome may be more accurate than the pancreatic cholera syndrome.", "contents": "Watery diarrhea syndrome. Two unusual cases and further evidence that VIP is a humoral mediator. Two unusual cases of the watery diarrhea syndrome are presented. In one patient an adrenal medullary tumor, a pheochromocytoma that produced vasoactive intestinal polypeptide (VIP) was excised with total relief of symptoms. The second patient a 65-year-old man with abrupt onset of massive watery diarrhea that led to acidosis and coma was symptomatically controlled for one year on 10 mg/day of prednisone. Elevated levels of VIP returned to normal after prednisone therapy was started. A benign islet cell tumor not localized by angiography was removed by distal pancreatic resection. Tissue levels of VIP were markedly elevated. VIP is a humoral mediator of the water diarrhea syndrome. Both benign and malignant pancreatic and extrapancreatic tumors may cause the watery diarrhea syndrome. Steroids may cause symptomatic relief of the diarrhea by lowering peptide levels to normal. The term watery diarrhea syndrome may be more accurate than the pancreatic cholera syndrome."}
{"id": "PMID:205180", "title": "Reappraisal of solitary bronchiolar (alveolar cell) carcinoma of the lung.", "content": "Twelve patients with solitary bronchiolar carcinoma had lobectomy and were followed for up to 16 years. The concept of a multicentric origin of bronchiolar carcinoma, maintained for more than eight decades, should be discarded. The neoplasm arises indolently and usually in an area of pulmonary fibrosis. After lobectomy patients can now expect to follow one of four courses: (1) to be alive and well without recurrence; (2) after several years to have pulmonary recurrence or a new carcinoma; (3) with minute spread at the time of lobectomy to have metastasis develop in a short period; or (4) to die of unrelated conditions. The overall 5-year survival with this tumor is about 75%. Late recurrence or the development of another primary tumor, however, prompts the need for prolonged follow-up. Immunologically, patients have circulating antibodies when well and demonstrable circulating antigens with recurrence. The survival rate of selected patients with solitary bronchiolar carcinoma (eliminating those patients with microscopic spread from the primary neoplasm at the time of resection and those dying of other causes) was 100% after 5 years and 75% after 10 years.", "contents": "Reappraisal of solitary bronchiolar (alveolar cell) carcinoma of the lung. Twelve patients with solitary bronchiolar carcinoma had lobectomy and were followed for up to 16 years. The concept of a multicentric origin of bronchiolar carcinoma, maintained for more than eight decades, should be discarded. The neoplasm arises indolently and usually in an area of pulmonary fibrosis. After lobectomy patients can now expect to follow one of four courses: (1) to be alive and well without recurrence; (2) after several years to have pulmonary recurrence or a new carcinoma; (3) with minute spread at the time of lobectomy to have metastasis develop in a short period; or (4) to die of unrelated conditions. The overall 5-year survival with this tumor is about 75%. Late recurrence or the development of another primary tumor, however, prompts the need for prolonged follow-up. Immunologically, patients have circulating antibodies when well and demonstrable circulating antigens with recurrence. The survival rate of selected patients with solitary bronchiolar carcinoma (eliminating those patients with microscopic spread from the primary neoplasm at the time of resection and those dying of other causes) was 100% after 5 years and 75% after 10 years."}
{"id": "PMID:205182", "title": "Influence of triethylcholine on autonomic transmission in vitro.", "content": "The influence of triethylcholine (TEC) on isolated autonomic transmission has been investigated in some isolated preparations. The guinea-pig hypogastric nerve-vas deferens-urinary bladder preparation for studying both cholinergic and adrenergic transmission simultaneously is described. Incubation with TEC caused impairment of cholinergic transmission but failed to inhibit adrenergic transmission. Employing TEC as a pharmacological tool, no evidence for a cholinergic link could be obtained in adrenergic transmission in the isolated vas deferens and rabbit ileum preparations.", "contents": "Influence of triethylcholine on autonomic transmission in vitro. The influence of triethylcholine (TEC) on isolated autonomic transmission has been investigated in some isolated preparations. The guinea-pig hypogastric nerve-vas deferens-urinary bladder preparation for studying both cholinergic and adrenergic transmission simultaneously is described. Incubation with TEC caused impairment of cholinergic transmission but failed to inhibit adrenergic transmission. Employing TEC as a pharmacological tool, no evidence for a cholinergic link could be obtained in adrenergic transmission in the isolated vas deferens and rabbit ileum preparations."}
{"id": "PMID:205183", "title": "Endometrial carcinoma following estrogen therapy for breast cancer. Report of three cases.", "content": "Three patients with metastatic breast cancer responded to diethylstilbestrol (DES) therapy, but later they developed endometrial carcinoma. Evidence is presented to support the hypothesis  that endometrial carcinoma can occur in breast cancer patients receiving diethylstilbestrol therapy.", "contents": "Endometrial carcinoma following estrogen therapy for breast cancer. Report of three cases. Three patients with metastatic breast cancer responded to diethylstilbestrol (DES) therapy, but later they developed endometrial carcinoma. Evidence is presented to support the hypothesis  that endometrial carcinoma can occur in breast cancer patients receiving diethylstilbestrol therapy."}
{"id": "PMID:205184", "title": "[Gastritis with hypoproteinemia in children. Relation to Menetrier's disease and cytomegalic inclusion disease].", "content": "The case report concerns a 2 years old girl with hypoproteinemia associated with gastritis. The child recovered completely 8 weeks later. Cytomegalovirus was excreted in urine. The authors suggest that such a clinical picture should not be called Menetrier's disease. The role of cytomegalovirus is discussed.", "contents": "[Gastritis with hypoproteinemia in children. Relation to Menetrier's disease and cytomegalic inclusion disease]. The case report concerns a 2 years old girl with hypoproteinemia associated with gastritis. The child recovered completely 8 weeks later. Cytomegalovirus was excreted in urine. The authors suggest that such a clinical picture should not be called Menetrier's disease. The role of cytomegalovirus is discussed."}
{"id": "PMID:205185", "title": "[Adenomegalic cytophagic sinusal histiocytosis. Morphological and immunologic study of a case].", "content": "The case of a 14-year-old boy of North-African origin, presenting a phagocytic sinus histiocytosis is reported. The main features of this now classical disease are illustrated: its localization to the neck, its chronicity, the fact that it is well tolerated, the pseudotumoral appearance of the adenomegaly as well as the intensive phagocytic (essentially lymphocytophagic) activity of the sinus macrophages. The bringing to light in a picture of hyperimmunity of an elevated percentage of antibodies against the measles and EB viruses, associated with a temporary depression of the cellular immunity, suggest that this lymphophagocytosis could be controlled and facilitated by preferential opsonization of lymphoid cells carrying on their membrane the antigen of the virus or viruses initially responsible.", "contents": "[Adenomegalic cytophagic sinusal histiocytosis. Morphological and immunologic study of a case]. The case of a 14-year-old boy of North-African origin, presenting a phagocytic sinus histiocytosis is reported. The main features of this now classical disease are illustrated: its localization to the neck, its chronicity, the fact that it is well tolerated, the pseudotumoral appearance of the adenomegaly as well as the intensive phagocytic (essentially lymphocytophagic) activity of the sinus macrophages. The bringing to light in a picture of hyperimmunity of an elevated percentage of antibodies against the measles and EB viruses, associated with a temporary depression of the cellular immunity, suggest that this lymphophagocytosis could be controlled and facilitated by preferential opsonization of lymphoid cells carrying on their membrane the antigen of the virus or viruses initially responsible."}
{"id": "PMID:205186", "title": "[Etiology and associations of pituitary dwarfism. Study of a series of 135 cases].", "content": "Among 135 consecutive cases of hypopituitary dwarfism, 42 related to detectable intracranial tumour or defect. In 13 cases the tumour had been previously operated and/or irradiated. In 29 others the defect was suggested by neurological abnormalities or headache, skull radiographs, ocular examination or by associated post-hypophyseal deficiency and was demonstrated by pneumoencephalography. When none of these associated abnormalities was found, pneumoencephalography failed to demonstrate any intracranial lesion. Among the 93 so-called idiopathic cases there was a large majority of males (60/93) with a history of birth difficulties (34/60) and especially of breech delivery (23/60). TSH, FSH/LH and ACTH deficiencies were associated to GH deficiency in 81% of patients with detectable intracranial lesions, 57% of male and 39% of female idiopathic cases. The number of patients with idiopathic isolated GH deficiency was similar in boys and girls, suggesting in them the hypothesis of a recessive autosomic genetic defect in spite of the scarcity of familial cases. Peculiar clinical associations may contribute to the diagnosis.", "contents": "[Etiology and associations of pituitary dwarfism. Study of a series of 135 cases]. Among 135 consecutive cases of hypopituitary dwarfism, 42 related to detectable intracranial tumour or defect. In 13 cases the tumour had been previously operated and/or irradiated. In 29 others the defect was suggested by neurological abnormalities or headache, skull radiographs, ocular examination or by associated post-hypophyseal deficiency and was demonstrated by pneumoencephalography. When none of these associated abnormalities was found, pneumoencephalography failed to demonstrate any intracranial lesion. Among the 93 so-called idiopathic cases there was a large majority of males (60/93) with a history of birth difficulties (34/60) and especially of breech delivery (23/60). TSH, FSH/LH and ACTH deficiencies were associated to GH deficiency in 81% of patients with detectable intracranial lesions, 57% of male and 39% of female idiopathic cases. The number of patients with idiopathic isolated GH deficiency was similar in boys and girls, suggesting in them the hypothesis of a recessive autosomic genetic defect in spite of the scarcity of familial cases. Peculiar clinical associations may contribute to the diagnosis."}
{"id": "PMID:205187", "title": "Necrotizing pancreatitis due to simian adenovirus type 31 in a rhesus monkey.", "content": "Simian adenovirus type 31 was isolated from pancreatic tissue of an 8-year-old male rhesus monkey that died as the result of acute necrotizing pancreatitis. Histologically, the pancreas showed wide-spread necrosis, extensive infiltration of polymorphonuclear leukocytes, and nuclear inclusions in pancreatic acinar cells. Large numbers of adenovirus particles were demonstrable in the acinar cells by electron microscopy. This is the second case of adenovirus-associated pancreatitis we have found in rhesus monkeys and the first case in which we attempted to isolate the virus. Our data indicate that adenovirus pancreatitis is a distinct entity in rhesus monkeys and may occur with greater frequency than is generally believed.", "contents": "Necrotizing pancreatitis due to simian adenovirus type 31 in a rhesus monkey. Simian adenovirus type 31 was isolated from pancreatic tissue of an 8-year-old male rhesus monkey that died as the result of acute necrotizing pancreatitis. Histologically, the pancreas showed wide-spread necrosis, extensive infiltration of polymorphonuclear leukocytes, and nuclear inclusions in pancreatic acinar cells. Large numbers of adenovirus particles were demonstrable in the acinar cells by electron microscopy. This is the second case of adenovirus-associated pancreatitis we have found in rhesus monkeys and the first case in which we attempted to isolate the virus. Our data indicate that adenovirus pancreatitis is a distinct entity in rhesus monkeys and may occur with greater frequency than is generally believed."}
{"id": "PMID:205188", "title": "Bile duct adenomas as liver nodules.", "content": "Bile duct adenomas can be difficult to differentiate at laparotomy from small metastatic tumor nodules in the liver. This can present a problem to the pathologist and surgeon relative to the advisability of attempted curative vs pallative surgery. We report two such cases. Review of our autopsy materials shows the incidence of bile duct adenoma to be higher than usually reported. Even though they all present as grayish-white, firm nodules, usually frozen section will reveal the true nature of the lesion. Occasionally, however, the lesions with active bile duct proliferation can cause problems in diagnosis, even after such examination. Accurate diagnosis by recognition of the entity and its histological characteristics may be very important in the surgical treatment of patients.", "contents": "Bile duct adenomas as liver nodules. Bile duct adenomas can be difficult to differentiate at laparotomy from small metastatic tumor nodules in the liver. This can present a problem to the pathologist and surgeon relative to the advisability of attempted curative vs pallative surgery. We report two such cases. Review of our autopsy materials shows the incidence of bile duct adenoma to be higher than usually reported. Even though they all present as grayish-white, firm nodules, usually frozen section will reveal the true nature of the lesion. Occasionally, however, the lesions with active bile duct proliferation can cause problems in diagnosis, even after such examination. Accurate diagnosis by recognition of the entity and its histological characteristics may be very important in the surgical treatment of patients."}
{"id": "PMID:205189", "title": "Mastectomy as an adjunct to combination chemotherapy.", "content": "Three patients with metastatic breast carcinoma who had untreated locally advanced primary tumors were treated initially with combination chemotherapy followed by hygienic mastectomy. There was marked regression of the primary tumor in each case after chemotherapy, allowing for a technically simpler mastectomy without skin grafts. There were no serious postoperative complications, or delay in the resumption of systemic chemotherapy in any of them. The postoperative chemotherapy produced complete disappearance of the distant metastases and the patients remain clinically free of disease without local recurrence for 21, 10, and 7 months, respectively. One of these patients had inflammatory carcinoma and did well with this combined approach. These findings suggest a rationale for such an approach in patients with inflammatory carcinoma and may be applicable to patients with stage III breast cancer in whom the primary tumors are locally advanced and technically difficult to resect.", "contents": "Mastectomy as an adjunct to combination chemotherapy. Three patients with metastatic breast carcinoma who had untreated locally advanced primary tumors were treated initially with combination chemotherapy followed by hygienic mastectomy. There was marked regression of the primary tumor in each case after chemotherapy, allowing for a technically simpler mastectomy without skin grafts. There were no serious postoperative complications, or delay in the resumption of systemic chemotherapy in any of them. The postoperative chemotherapy produced complete disappearance of the distant metastases and the patients remain clinically free of disease without local recurrence for 21, 10, and 7 months, respectively. One of these patients had inflammatory carcinoma and did well with this combined approach. These findings suggest a rationale for such an approach in patients with inflammatory carcinoma and may be applicable to patients with stage III breast cancer in whom the primary tumors are locally advanced and technically difficult to resect."}
{"id": "PMID:205190", "title": "Amebic peritonitis following rupture of an amebic liver abscess. Successful treatment of two patients.", "content": "We present two successfully treated cases of amebic peritonitis. Acute peritonitis secondary to intra-abdominal rupture of an amebic liver abscess is an infrequent but serious complication of invasive amebiasis. Its diagnosis should be considered in anyone with a suspected liver abscess, jaundice, or diarrhea in whom peritonitis develops. This diagnosis should be further suggested in the United States if the patient is a male and is of Mexican origin in areas where this racial group constitutes the majority of cases of amebic disease. Use of radioisotope liver scans and the demonstration of serum precipitins to Endamoeba histolytica may provide rapid evidence of invasive disease, although surgical intervention is often necessary to make a specific diagnosis. Emetine hydrochloride alone or followed by metronidazole combined with surgical drainage is the current treatment for amebic peritonitis.", "contents": "Amebic peritonitis following rupture of an amebic liver abscess. Successful treatment of two patients. We present two successfully treated cases of amebic peritonitis. Acute peritonitis secondary to intra-abdominal rupture of an amebic liver abscess is an infrequent but serious complication of invasive amebiasis. Its diagnosis should be considered in anyone with a suspected liver abscess, jaundice, or diarrhea in whom peritonitis develops. This diagnosis should be further suggested in the United States if the patient is a male and is of Mexican origin in areas where this racial group constitutes the majority of cases of amebic disease. Use of radioisotope liver scans and the demonstration of serum precipitins to Endamoeba histolytica may provide rapid evidence of invasive disease, although surgical intervention is often necessary to make a specific diagnosis. Emetine hydrochloride alone or followed by metronidazole combined with surgical drainage is the current treatment for amebic peritonitis."}
{"id": "PMID:205191", "title": "Pseudolymphoma in renal allograft recipients.", "content": "Five renal transplant recipients exhibited giant systemic lymphadenopathy shortly after transplantation. Biopsy specimens did not show Hodgkin's lymphoma. Immunosuppression was continued in all patients. In contrast to the rapidly fatal course of malignant lymphoma in transplant recipients, adenopathy in these five patients has uniformly resolved. Patients have been observed for 6 to 15 months with no evidence of residual disease. Interval biopsy specimens are not malignant. Each patient received antithymocyte globulin from a single lot for 10 to 21 days after transplantation. During administration, T cell lymphocytes were suppressed to 5% of control values. When lymphadenopathy occurred, T cell values rebounded to 371% of control values. Toxoplasmosis titers as well as viral cultures of lymph node biopsy specimens were negative. These data indicate a benign course of this histologically malignant disease and suggest a lymphoblastic rebound phenomenon to antithymocyte globulin.", "contents": "Pseudolymphoma in renal allograft recipients. Five renal transplant recipients exhibited giant systemic lymphadenopathy shortly after transplantation. Biopsy specimens did not show Hodgkin's lymphoma. Immunosuppression was continued in all patients. In contrast to the rapidly fatal course of malignant lymphoma in transplant recipients, adenopathy in these five patients has uniformly resolved. Patients have been observed for 6 to 15 months with no evidence of residual disease. Interval biopsy specimens are not malignant. Each patient received antithymocyte globulin from a single lot for 10 to 21 days after transplantation. During administration, T cell lymphocytes were suppressed to 5% of control values. When lymphadenopathy occurred, T cell values rebounded to 371% of control values. Toxoplasmosis titers as well as viral cultures of lymph node biopsy specimens were negative. These data indicate a benign course of this histologically malignant disease and suggest a lymphoblastic rebound phenomenon to antithymocyte globulin."}
{"id": "PMID:205192", "title": "Malignant histiocytomas.", "content": "During the past ten years, the histiogenesis of malignant histiocytomas and a group of related benign and malignant lesions have been the source of speculation. Although of heterogeneous histological appearance, it is believed that there is a common cell of origin for these neoplasms--the histiocyte. From 1966 to 1974, 16 patients were encountered who had neoplasms that fell into the general group of malignant histiocytomas. These tumors were variously located in the extremities, head, chest wall, retroperitoneum, lung, spermatic cord, and lower abdomen. Surgical treatment included radical amputations, wide local excision, pulmonary lobectomy, and nephrectomy. Cobalt therapy and chemotherapy with vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride, and chlorambucil were also used. Ten of 16 patients are alive after treatment, two are alive with metastatic disease, but four have died of malignant disease.", "contents": "Malignant histiocytomas. During the past ten years, the histiogenesis of malignant histiocytomas and a group of related benign and malignant lesions have been the source of speculation. Although of heterogeneous histological appearance, it is believed that there is a common cell of origin for these neoplasms--the histiocyte. From 1966 to 1974, 16 patients were encountered who had neoplasms that fell into the general group of malignant histiocytomas. These tumors were variously located in the extremities, head, chest wall, retroperitoneum, lung, spermatic cord, and lower abdomen. Surgical treatment included radical amputations, wide local excision, pulmonary lobectomy, and nephrectomy. Cobalt therapy and chemotherapy with vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride, and chlorambucil were also used. Ten of 16 patients are alive after treatment, two are alive with metastatic disease, but four have died of malignant disease."}
{"id": "PMID:205193", "title": "DNA repair processes in germ cells demonstrated in ejaculated sperms of rabbits treated with methyl methane sulfonate.", "content": "Male rabbits were treated with a single i.v. injection of 22.5 mg/kg methyl methane sulfonate (MMS). 0--24 h later [3H]-thymidine was injected in both testicles. Incorporation of the isotope in germ cell DNA was demonstrated in ejaculated sperms. In controls labeled sperms were demonstrated first on day 40--43. These cells were in the preleptotene spermatocyte phase at the time of [3H]-thmidine injection. In rabbits treated with MMS significant radioactivity occurred in sperms collected from day 19 onwards. These cells were in late spermatocyte and early spermatid phase of maturation when [3H]-thymidine was injected. Incorporation of thymidine in these cell populations is interpreted as an expression of unscheduled DNA synthesis, a repair process initiated after chemical damage of germ cell DNA by MMS. The usefulness of the rabbit test system within the framework of conventional mutagenicity screening tests is discussed.", "contents": "DNA repair processes in germ cells demonstrated in ejaculated sperms of rabbits treated with methyl methane sulfonate. Male rabbits were treated with a single i.v. injection of 22.5 mg/kg methyl methane sulfonate (MMS). 0--24 h later [3H]-thymidine was injected in both testicles. Incorporation of the isotope in germ cell DNA was demonstrated in ejaculated sperms. In controls labeled sperms were demonstrated first on day 40--43. These cells were in the preleptotene spermatocyte phase at the time of [3H]-thmidine injection. In rabbits treated with MMS significant radioactivity occurred in sperms collected from day 19 onwards. These cells were in late spermatocyte and early spermatid phase of maturation when [3H]-thymidine was injected. Incorporation of thymidine in these cell populations is interpreted as an expression of unscheduled DNA synthesis, a repair process initiated after chemical damage of germ cell DNA by MMS. The usefulness of the rabbit test system within the framework of conventional mutagenicity screening tests is discussed."}
{"id": "PMID:205194", "title": "The effect of ascorbic acid on infection chick-embryo ciliated tracheal organ cultures by coronavirus.", "content": "Chick embryo tracheal organ cultures showed increased resistance to infection by a coronavirus after exposure to ascorbate, while chick respiratory epithelium and allantois-on-shell preparations showed no increase in resistance to infection by an influenza virus or a paramyxovirus.", "contents": "The effect of ascorbic acid on infection chick-embryo ciliated tracheal organ cultures by coronavirus. Chick embryo tracheal organ cultures showed increased resistance to infection by a coronavirus after exposure to ascorbate, while chick respiratory epithelium and allantois-on-shell preparations showed no increase in resistance to infection by an influenza virus or a paramyxovirus."}
{"id": "PMID:205195", "title": "Size and secondary structure of avian myeloblastosis virus associated ribosomal RNA: comparison with cellular and precursor ribosomal RNA.", "content": "Ribosomal RNA isolated from ribosomes present inside avian myeloblastosis virus (AMV) was characterized by electron microscopy using the formamide-urea spreading technique. The molecular weight and the secondary structures were compared with those of r-RNA and precursor r-NA isolated from host cells, the leukemic myeloblasts. The molecular weight of viral r-RNA (1.62 +/- 0.18 X 10(6) and 0.69 +/- 0.10 X 10(6)) and the molecular weight of cellular r-RNA (1.63 +/- 0.18 X 10(6) and 0.67 +/- 0.09 X 10(6)), the latter obtained from avian myeloblasts, were found to be identical and comparable with the molecular weight of chicken liver r-RNA. Likewise, the secondary structures of viral r-RNA were identical to those of cellular r-RNA. The postulated possible precursor character of viral r-RNA was excluded, since the molecules of viral r-RNA do not show any similarity to those of precursor r-RNA. Previously observed differences in behavior of viral and cellular (myeloblastic) r-RNA in sedimentation and electrophoretic mobility are discussed.", "contents": "Size and secondary structure of avian myeloblastosis virus associated ribosomal RNA: comparison with cellular and precursor ribosomal RNA. Ribosomal RNA isolated from ribosomes present inside avian myeloblastosis virus (AMV) was characterized by electron microscopy using the formamide-urea spreading technique. The molecular weight and the secondary structures were compared with those of r-RNA and precursor r-NA isolated from host cells, the leukemic myeloblasts. The molecular weight of viral r-RNA (1.62 +/- 0.18 X 10(6) and 0.69 +/- 0.10 X 10(6)) and the molecular weight of cellular r-RNA (1.63 +/- 0.18 X 10(6) and 0.67 +/- 0.09 X 10(6)), the latter obtained from avian myeloblasts, were found to be identical and comparable with the molecular weight of chicken liver r-RNA. Likewise, the secondary structures of viral r-RNA were identical to those of cellular r-RNA. The postulated possible precursor character of viral r-RNA was excluded, since the molecules of viral r-RNA do not show any similarity to those of precursor r-RNA. Previously observed differences in behavior of viral and cellular (myeloblastic) r-RNA in sedimentation and electrophoretic mobility are discussed."}
{"id": "PMID:205196", "title": "Effect of serum on the antiviral and anticellular activities of mouse interferon.", "content": "Fetal bovine serum markedly decreased the ability of mouse L-929 interferon preparations to inhibit the formation of L-929 clones, but did not affect their ability to inhibit vesicular stomatitis virus (VSV) plaque formation in these cells. This dissociation of effects by interferon preparations indicates that: 1. the mechanism of action of interferon for its anticlonal antiviral activities is different; or 2. the molecule responsible for the anticlonal activity is a separate growth inhibitory factor.", "contents": "Effect of serum on the antiviral and anticellular activities of mouse interferon. Fetal bovine serum markedly decreased the ability of mouse L-929 interferon preparations to inhibit the formation of L-929 clones, but did not affect their ability to inhibit vesicular stomatitis virus (VSV) plaque formation in these cells. This dissociation of effects by interferon preparations indicates that: 1. the mechanism of action of interferon for its anticlonal antiviral activities is different; or 2. the molecule responsible for the anticlonal activity is a separate growth inhibitory factor."}
{"id": "PMID:205197", "title": "Induction capacity and influence of dThdMP on thymidine kinase activity of type 1 and 2 strains of herpes simplex virus.", "content": "The thymidine kinase inducing ability of 104 strains of herpes simplex virus was studied comparatively. A pronounced relationship was established between induction of the enzyme and the serotype of the strains. As a rule, the strains of serotype 2 are weaker inducer of dThd- and dCyd-kinase activity than serotype 1 strains. A certain parallelism exists between induction of both enzymes, however the activity of the thymidine kinase increases after infection with herpes simplex virus 4--5 times more than that of the dCyd-kinase. Adaptation of the strains to cell cultures only slightly modifies the inducing ability of the herpes simplex virus strains. The thymidine kinase activity induced by HSV-1 and HSV-2 differ from each other and are different from the cell enzyme with respect to their thermal stability at 40 degrees C. These differences are expressed more clearly in the presence of 480 muM dThdMP during inactivation. dThdMP stabilizes the type 1 but not the type 2 enzyme.", "contents": "Induction capacity and influence of dThdMP on thymidine kinase activity of type 1 and 2 strains of herpes simplex virus. The thymidine kinase inducing ability of 104 strains of herpes simplex virus was studied comparatively. A pronounced relationship was established between induction of the enzyme and the serotype of the strains. As a rule, the strains of serotype 2 are weaker inducer of dThd- and dCyd-kinase activity than serotype 1 strains. A certain parallelism exists between induction of both enzymes, however the activity of the thymidine kinase increases after infection with herpes simplex virus 4--5 times more than that of the dCyd-kinase. Adaptation of the strains to cell cultures only slightly modifies the inducing ability of the herpes simplex virus strains. The thymidine kinase activity induced by HSV-1 and HSV-2 differ from each other and are different from the cell enzyme with respect to their thermal stability at 40 degrees C. These differences are expressed more clearly in the presence of 480 muM dThdMP during inactivation. dThdMP stabilizes the type 1 but not the type 2 enzyme."}
{"id": "PMID:205198", "title": "Neurovirulence in cynomolgus monkeys of enterovirus 71 isolated from a patient with hand, foot and mouth disease.", "content": "Six cynomolgus monkeys were inoculated subcutaneously with enteroviurs 71 (E71), isolated from the stools of a patient with hand, foot and mouth disease (HFMD). Clinical symptoms were observed in three of the six monkeys. One monkey showed complete paralysis of the lower extremities and two animals showed weakness in the hind limbs 4 to 7 days after inoculation. Lesions were found in the central nervous system (CNS) of all monkeys. Mild to moderate vascular lesions, perivascular cuffings, degeneration and disappearance of the neurons and meningial lymphocytic infiltration were observed in the grey and/or white matter of the spinal cord, medulla oblongata, cerebral cortex and brain stem. No virus was recovered from the CNS or liver of any of the six monkeys. However, serum neutralizing antibody titers had risen in monkeys inoculated with E71.", "contents": "Neurovirulence in cynomolgus monkeys of enterovirus 71 isolated from a patient with hand, foot and mouth disease. Six cynomolgus monkeys were inoculated subcutaneously with enteroviurs 71 (E71), isolated from the stools of a patient with hand, foot and mouth disease (HFMD). Clinical symptoms were observed in three of the six monkeys. One monkey showed complete paralysis of the lower extremities and two animals showed weakness in the hind limbs 4 to 7 days after inoculation. Lesions were found in the central nervous system (CNS) of all monkeys. Mild to moderate vascular lesions, perivascular cuffings, degeneration and disappearance of the neurons and meningial lymphocytic infiltration were observed in the grey and/or white matter of the spinal cord, medulla oblongata, cerebral cortex and brain stem. No virus was recovered from the CNS or liver of any of the six monkeys. However, serum neutralizing antibody titers had risen in monkeys inoculated with E71."}
{"id": "PMID:205199", "title": "[Reverse plaque formation by hog cholera virus inducing interference with VSV (author's transl)].", "content": "Infection of PK15 cells with various strains of Hog Cholera (HCV, togaviridae) induces a transient refractory state to VSV. The reverse plaque procedure is convenient for HCV titration of virulent, \"chronic\" and attenuated strains.", "contents": "[Reverse plaque formation by hog cholera virus inducing interference with VSV (author's transl)]. Infection of PK15 cells with various strains of Hog Cholera (HCV, togaviridae) induces a transient refractory state to VSV. The reverse plaque procedure is convenient for HCV titration of virulent, \"chronic\" and attenuated strains."}
{"id": "PMID:205201", "title": "Spinal intramedullary glioblastoma with intracranial seeding. Report of a case.", "content": "Approximately one year after partial removal of an intramedullary glioblastoma at T12, a patient was admitted to Wadsworth Veterans Administration Hospital with signs and symptoms of an intracranial tumor. We describe the unusual occurrence of intracranial seeding from spinal glioblastoma and review this rare condition and the possible mechanism involved.", "contents": "Spinal intramedullary glioblastoma with intracranial seeding. Report of a case. Approximately one year after partial removal of an intramedullary glioblastoma at T12, a patient was admitted to Wadsworth Veterans Administration Hospital with signs and symptoms of an intracranial tumor. We describe the unusual occurrence of intracranial seeding from spinal glioblastoma and review this rare condition and the possible mechanism involved."}
{"id": "PMID:205202", "title": "[Oedematous optic neuropathy from Perhexilline maleate associated with peripheral polyneuropathy (author's transl)].", "content": "The authors report on a polyradiculoneuropathy related to long-term treatment with Perhexiline maleate (a drug used in France since 1973 for coronary insufficiency) whose presenting sign is a bilateral aedematous optic neuropathy. The mechanism of this effect on the optic nerves and on papilloedema is discussed; it seems not to be caused by a direct toxic action on the optic fibres but by the existence of chronic intracranial hypertension.", "contents": "[Oedematous optic neuropathy from Perhexilline maleate associated with peripheral polyneuropathy (author's transl)]. The authors report on a polyradiculoneuropathy related to long-term treatment with Perhexiline maleate (a drug used in France since 1973 for coronary insufficiency) whose presenting sign is a bilateral aedematous optic neuropathy. The mechanism of this effect on the optic nerves and on papilloedema is discussed; it seems not to be caused by a direct toxic action on the optic fibres but by the existence of chronic intracranial hypertension."}
{"id": "PMID:205203", "title": "Effects of rapidly rotating shifts on sleep patterns and sleep structure.", "content": "Six young adult males were assigned to a rapidly rotating shift work schedule (2 d 6 am-4 pm, 2 d 4 pm-10 pm, and 2 d 10 pm-6 am). They lived in the laboratory and completed two rotations. Their nonshift activities were ad libitum including sleep times. The patterns and structure of sleep were analyzed. Shift times systematically affected sleep patterns. Within shifts, Ss slept as late as possible prior to the morning shift, went to bed shortly after the night shift, and slept approximately midway between shifts on the afternoon shift. In transitioning to a new shift, the new shift time tended to determine sleep time. Sleep was significantly longer in transitions between shifts. Sleep structure was not markedly changed.", "contents": "Effects of rapidly rotating shifts on sleep patterns and sleep structure. Six young adult males were assigned to a rapidly rotating shift work schedule (2 d 6 am-4 pm, 2 d 4 pm-10 pm, and 2 d 10 pm-6 am). They lived in the laboratory and completed two rotations. Their nonshift activities were ad libitum including sleep times. The patterns and structure of sleep were analyzed. Shift times systematically affected sleep patterns. Within shifts, Ss slept as late as possible prior to the morning shift, went to bed shortly after the night shift, and slept approximately midway between shifts on the afternoon shift. In transitioning to a new shift, the new shift time tended to determine sleep time. Sleep was significantly longer in transitions between shifts. Sleep structure was not markedly changed."}
{"id": "PMID:205204", "title": "Spindle cell lipoma (report of 2 cases and differential diagnosis).", "content": "\"Spindle Cell Limpoma\" is a benign tumor consisting of immature mesenchymal spindle cells with occasional collagen fibers, myxoid areas and lipocytes scattered throughout in varying numbers. Only focally it shows the typical appearance of a lipoma. Therefore it may be confused with liposarcoma, fibrosing lipoma, furthermore with areas of fibrous histiocytoma or nodular fasciitis showing fat infiltration.", "contents": "Spindle cell lipoma (report of 2 cases and differential diagnosis). \"Spindle Cell Limpoma\" is a benign tumor consisting of immature mesenchymal spindle cells with occasional collagen fibers, myxoid areas and lipocytes scattered throughout in varying numbers. Only focally it shows the typical appearance of a lipoma. Therefore it may be confused with liposarcoma, fibrosing lipoma, furthermore with areas of fibrous histiocytoma or nodular fasciitis showing fat infiltration."}
{"id": "PMID:205207", "title": "Vitamin D metabolism and expression in rats fed on low-calcium and low-phosphorus diets.", "content": "1. Cholecalciferol, radioactively labelled with both (14)C and (3)H, was administered weekly for 7 weeks to rats that had been depleted of vitamin D for 4 weeks before repletion with the radioactive vitamin. This permitted measurement of the steady-state effect on vitamin D metabolism of low-calcium and low-phosphorus regimens, as compared with a normal mineral intake. These dietary manoeuvres were carried out during the last 3 weeks of repletion. Cholecalciferol, 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol were determined in plasma, intestine, kidney and bone. Ca(2+)-binding-protein content was measured in intestine and kidneys of comparable animals. 2. In rats on the low-calcium diets, 1,25-dihydroxycholecalciferol concentration was elevated in plasma, bone, kidney and intestine, and intestinal Ca(2+)-binding protein was increased to over twice the concentration found in the control animals. 3. The low-phosphorus regimens led to a decrease in plasma phosphate and 1,25-dihydroxycholecalciferol in all tissues studied, for the latter to the point where it was undetectable in plasma and bone. Intestinal and renal concentrations of Ca(2+)-binding protein were unchanged in the low-phosphate-intake group and decreased in the very-low-phosphate-intake group. 4. It is concluded that in the rat, unlike in the chick, hypophosphataemia is not associated with a stimulation of the production of 1,25-dihydroxycholecalciferol or its expression in the synthesis of Ca(2+)-binding protein. Therefore the plasma phosphate concentration does not appear to be directly involved in the regulation of the functional metabolism of vitamin D.", "contents": "Vitamin D metabolism and expression in rats fed on low-calcium and low-phosphorus diets. 1. Cholecalciferol, radioactively labelled with both (14)C and (3)H, was administered weekly for 7 weeks to rats that had been depleted of vitamin D for 4 weeks before repletion with the radioactive vitamin. This permitted measurement of the steady-state effect on vitamin D metabolism of low-calcium and low-phosphorus regimens, as compared with a normal mineral intake. These dietary manoeuvres were carried out during the last 3 weeks of repletion. Cholecalciferol, 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol were determined in plasma, intestine, kidney and bone. Ca(2+)-binding-protein content was measured in intestine and kidneys of comparable animals. 2. In rats on the low-calcium diets, 1,25-dihydroxycholecalciferol concentration was elevated in plasma, bone, kidney and intestine, and intestinal Ca(2+)-binding protein was increased to over twice the concentration found in the control animals. 3. The low-phosphorus regimens led to a decrease in plasma phosphate and 1,25-dihydroxycholecalciferol in all tissues studied, for the latter to the point where it was undetectable in plasma and bone. Intestinal and renal concentrations of Ca(2+)-binding protein were unchanged in the low-phosphate-intake group and decreased in the very-low-phosphate-intake group. 4. It is concluded that in the rat, unlike in the chick, hypophosphataemia is not associated with a stimulation of the production of 1,25-dihydroxycholecalciferol or its expression in the synthesis of Ca(2+)-binding protein. Therefore the plasma phosphate concentration does not appear to be directly involved in the regulation of the functional metabolism of vitamin D."}
{"id": "PMID:205208", "title": "Effects of pent-4-enoate on cellular redox state, glycolysis and fatty acid oxidation in isolated perfused rat heart.", "content": "The metabolic effects of pent-4-enoate were studied in beating and potassium-arrested perfused rat hearts. The addition of 0.8mm-pent-4-enoate to the fluid used to perfuse a potassium-arrested heart resulted in a 70% increase in the O(2) consumption and a 66% decrease in the glycolytic flux as measured in terms of the de-tritiation of [3-(3)H]glucose, although the proportion of the O(2) consumption attributable to glucose oxidation decreased from an initial 30% to 10%. The pent-4-enoate-induced increase in O(2) consumption was only 15% in the beating heart. In the potassium-arrested heart, pent-4-enoate stimulated palmitate oxidation by more than 100% when measured in terms of the production of (14)CO(2) from [1-(14)C]palmitate, but in the beating heart palmitate oxidation was inhibited. Perfusion of the heart with pent-4-enoate had no effect on the proportion of pyruvate dehydrogenase found in the active form, in spite of large changes in the CoASH and acetyl-CoA concentrations and changes in their concentration ratios. The effects of pent-4-enoate on the cellular redox state were dependent on the ATP consumption of the heart. In the beating heart, pent-4-enoate caused a rapid mitochondrial NAD(+) reduction that subsequently faded out, so that the final state was more oxidized than the initial state. The arrested heart, however, remained in a more reduced state than initially, even after the partial re-oxidation that followed the initial rapid NAD(+) reduction. The ability of pent-4-enoate to increase or decrease fatty acid oxidation can be explained on the basis of the differential effects of pent-4-enoate on the concentration of citric acid-cycle intermediates under conditions of high or low ATP consumption of the myocardial cell. The proportion of the fatty acids in the fuel consumed by the heart is probably primarily determined by the regulatory mechanisms of glycolysis. When pent-4-enoate causes an increase in the citric acid-cycle intermediates, feedback inhibition of glycolysis results in an increase in the oxidation of fatty acids.", "contents": "Effects of pent-4-enoate on cellular redox state, glycolysis and fatty acid oxidation in isolated perfused rat heart. The metabolic effects of pent-4-enoate were studied in beating and potassium-arrested perfused rat hearts. The addition of 0.8mm-pent-4-enoate to the fluid used to perfuse a potassium-arrested heart resulted in a 70% increase in the O(2) consumption and a 66% decrease in the glycolytic flux as measured in terms of the de-tritiation of [3-(3)H]glucose, although the proportion of the O(2) consumption attributable to glucose oxidation decreased from an initial 30% to 10%. The pent-4-enoate-induced increase in O(2) consumption was only 15% in the beating heart. In the potassium-arrested heart, pent-4-enoate stimulated palmitate oxidation by more than 100% when measured in terms of the production of (14)CO(2) from [1-(14)C]palmitate, but in the beating heart palmitate oxidation was inhibited. Perfusion of the heart with pent-4-enoate had no effect on the proportion of pyruvate dehydrogenase found in the active form, in spite of large changes in the CoASH and acetyl-CoA concentrations and changes in their concentration ratios. The effects of pent-4-enoate on the cellular redox state were dependent on the ATP consumption of the heart. In the beating heart, pent-4-enoate caused a rapid mitochondrial NAD(+) reduction that subsequently faded out, so that the final state was more oxidized than the initial state. The arrested heart, however, remained in a more reduced state than initially, even after the partial re-oxidation that followed the initial rapid NAD(+) reduction. The ability of pent-4-enoate to increase or decrease fatty acid oxidation can be explained on the basis of the differential effects of pent-4-enoate on the concentration of citric acid-cycle intermediates under conditions of high or low ATP consumption of the myocardial cell. The proportion of the fatty acids in the fuel consumed by the heart is probably primarily determined by the regulatory mechanisms of glycolysis. When pent-4-enoate causes an increase in the citric acid-cycle intermediates, feedback inhibition of glycolysis results in an increase in the oxidation of fatty acids."}
{"id": "PMID:205209", "title": "Quantitative electron-paramagnetic-resonance measurements of the electron-transfer components of the photosystem-I reaction centre.", "content": "E.p.r. spectrometry was used to investigate the quantitative relationships between the oxidized chlorophyll free-radical signal I and the reduced iron-sulphur centre-A signal generated on illuminating Photosystem-I particles at cryogenic temperatures. In Photosystem-I particles prepared by using the French press or Triton X-100, at pH8.0 in the presence and absence of ascorbate and at pH 10.0 in the presence of ascorbate, the size of the light-induced signal I and iron-sulphur centre-A signals, corresponded to equal numbers of unpaired electron spins in each component. At 77K the spin-lattice relaxation time, T1, of the free radical signal I in samples of Photosystem-I particles prepared with Triton X-100 in the absence of ascorbate was 0.68 times the T1 value in the presence of ascorbate. Such changes in relaxation time can account for the different quantitative conclusions incorrectly arrived at from measurements made at saturating microwave powers [Bearden & Malkin (1976) Biochem. Biophys. Acta 430, 538-547; Malkin & Bearden (1976) FEBS Lett. 69, 216-220]. In the presence of benzoquinone and ferricyanide the ratio of free radical to centre A was 2.96:1, and at 77K the T1 was 0.50 times the T1 for ascorbate-treated samples. Here free radicals from bulk chlorophyll are generated in addition to those from the reaction-centre chlorophyll.", "contents": "Quantitative electron-paramagnetic-resonance measurements of the electron-transfer components of the photosystem-I reaction centre. E.p.r. spectrometry was used to investigate the quantitative relationships between the oxidized chlorophyll free-radical signal I and the reduced iron-sulphur centre-A signal generated on illuminating Photosystem-I particles at cryogenic temperatures. In Photosystem-I particles prepared by using the French press or Triton X-100, at pH8.0 in the presence and absence of ascorbate and at pH 10.0 in the presence of ascorbate, the size of the light-induced signal I and iron-sulphur centre-A signals, corresponded to equal numbers of unpaired electron spins in each component. At 77K the spin-lattice relaxation time, T1, of the free radical signal I in samples of Photosystem-I particles prepared with Triton X-100 in the absence of ascorbate was 0.68 times the T1 value in the presence of ascorbate. Such changes in relaxation time can account for the different quantitative conclusions incorrectly arrived at from measurements made at saturating microwave powers [Bearden & Malkin (1976) Biochem. Biophys. Acta 430, 538-547; Malkin & Bearden (1976) FEBS Lett. 69, 216-220]. In the presence of benzoquinone and ferricyanide the ratio of free radical to centre A was 2.96:1, and at 77K the T1 was 0.50 times the T1 for ascorbate-treated samples. Here free radicals from bulk chlorophyll are generated in addition to those from the reaction-centre chlorophyll."}
{"id": "PMID:205210", "title": "Quantitative electron-paramagnetic-resonance measurements of the electron-transfer components of the photosystem-I reaction centre. The reaction-centre chlorophyll (P700), the primary electron acceptor X and bound iron-sulphur centre A.", "content": "An e.p.r. spectrum of the reduced form of the electron-transport component (X), thought to be the primary electron acceptor of Photosystem I, was obtained. By using line-shape simulations of this component and the free-radical e.p.r. signal I of the oxidized reaction-centre chlorophyll (P700), it was possible to determine the ratio of the number of electron spins to which these signals correspond in Photosystem-I particles under a variety of conditions. On illumination at cryogenic temperatures of Photosystem-I preparations, in which both bound iron-sulphur centres A and B were reduced, the measured ratio of free radical to component X varied between 1.04 and 2.23, with an average value of 1.54 +/- 0.18 where a Gaussian line-shape is assumed for the component-X signal in the simulation. The error in this measurement is estimated to be up to 50%. In a similar way component X and centre A of the bound iron-sulphur protein were quantified, the ratio between these two components varying between 1.26 and 0.61 with an average value of 0.75 +/- 0.06. These results indicate that the quantitative relationship, in terms of net electron spins, between centre A, component X and P700 is of the order to be expected if component X is indeed the primary electron acceptor in Photosystem I and a component of the photosynthetic electron-transport chain.", "contents": "Quantitative electron-paramagnetic-resonance measurements of the electron-transfer components of the photosystem-I reaction centre. The reaction-centre chlorophyll (P700), the primary electron acceptor X and bound iron-sulphur centre A. An e.p.r. spectrum of the reduced form of the electron-transport component (X), thought to be the primary electron acceptor of Photosystem I, was obtained. By using line-shape simulations of this component and the free-radical e.p.r. signal I of the oxidized reaction-centre chlorophyll (P700), it was possible to determine the ratio of the number of electron spins to which these signals correspond in Photosystem-I particles under a variety of conditions. On illumination at cryogenic temperatures of Photosystem-I preparations, in which both bound iron-sulphur centres A and B were reduced, the measured ratio of free radical to component X varied between 1.04 and 2.23, with an average value of 1.54 +/- 0.18 where a Gaussian line-shape is assumed for the component-X signal in the simulation. The error in this measurement is estimated to be up to 50%. In a similar way component X and centre A of the bound iron-sulphur protein were quantified, the ratio between these two components varying between 1.26 and 0.61 with an average value of 0.75 +/- 0.06. These results indicate that the quantitative relationship, in terms of net electron spins, between centre A, component X and P700 is of the order to be expected if component X is indeed the primary electron acceptor in Photosystem I and a component of the photosynthetic electron-transport chain."}
{"id": "PMID:205211", "title": "The oxidative activities of membrane vesicles from Bacillus caldolyticus. Energy-dependence of succinate oxidation.", "content": "1. The properties of membrane vesicles from the extreme thermophile Bacillus caldolyticus were investigated. 2. Vesicles prepared by exposure of spheroplasts to ultrasound contained cytochromes a, b and c, and at 50 degrees C they rapidly oxidized NADH and ascorbate in the presence of tetramethyl-p-phenylenediamine. Succinate and l-malate were oxidized more slowly, and dl-lactate, l-alanine and glycerol 1-phosphate were not oxidized. 3. In the absence of proton-conducting uncouplers the oxidation of NADH was accompanied by a net translocation of H(+) into the vesicles. Hydrolysis of ATP by a dicyclohexylcarbodi-imide-sensitive adenosine triphosphatase was accompanied by a similarly directed net translocation of H(+). 4. Uncouplers (carbonyl cyanide p-trifluoromethoxyphenylhydrazone or valinomycin plus NH(4) (+)) prevented net H(+) translocation but stimulated ATP hydrolysis, NADH oxidation and ascorbate oxidation. The last result suggested an energy-conserving site in the respiratory chain between cytochrome c and oxygen. 5. Under anaerobic conditions the reduction of cytochrome b by ascorbate (with tetramethyl-p-phenylenediamine) was stimulated by ATP hydrolysis, indicating an energy-conserving site between cytochrome b and cytochrome c. However, no reduction of NAD(+) supported by oxidation of succinate, malate or ascorbate occurred, neither did it with these substrates in the presence of ATP under anaerobic conditions, suggesting that there was no energy-conserving site between NADH and cytochrome b. 6. Succinate oxidation, in contrast with that of NADH and ascorbate, was strongly inhibited by uncouplers and stimulated by ATP hydrolysis. These effects were not observed when phenazine methosulphate, which transfers electrons from succinate dehydrogenase directly to oxygen, was present. It was concluded that in these vesicles the oxidation of succinate was energy-dependent and that the reoxidation of reduced succinate dehydrogenase was dependent on the outward movement of H(+) by the protonmotive force. 7. In support of the foregoing conclusion it was shown that the reduction of fumarate by NADH was an energy-conserving process. 8. If the activities of vesicles accurately represent those of the intact organism it appears that in B. caldolyticus the reduction of fumarate to succinate at the expense of reducing equivalents from NADH is energetically favoured over succinate oxidation even under aerobic conditions. This may be related to the need for an ample supply of succinate for haem synthesis in order to provide cytochromes for the organism.", "contents": "The oxidative activities of membrane vesicles from Bacillus caldolyticus. Energy-dependence of succinate oxidation. 1. The properties of membrane vesicles from the extreme thermophile Bacillus caldolyticus were investigated. 2. Vesicles prepared by exposure of spheroplasts to ultrasound contained cytochromes a, b and c, and at 50 degrees C they rapidly oxidized NADH and ascorbate in the presence of tetramethyl-p-phenylenediamine. Succinate and l-malate were oxidized more slowly, and dl-lactate, l-alanine and glycerol 1-phosphate were not oxidized. 3. In the absence of proton-conducting uncouplers the oxidation of NADH was accompanied by a net translocation of H(+) into the vesicles. Hydrolysis of ATP by a dicyclohexylcarbodi-imide-sensitive adenosine triphosphatase was accompanied by a similarly directed net translocation of H(+). 4. Uncouplers (carbonyl cyanide p-trifluoromethoxyphenylhydrazone or valinomycin plus NH(4) (+)) prevented net H(+) translocation but stimulated ATP hydrolysis, NADH oxidation and ascorbate oxidation. The last result suggested an energy-conserving site in the respiratory chain between cytochrome c and oxygen. 5. Under anaerobic conditions the reduction of cytochrome b by ascorbate (with tetramethyl-p-phenylenediamine) was stimulated by ATP hydrolysis, indicating an energy-conserving site between cytochrome b and cytochrome c. However, no reduction of NAD(+) supported by oxidation of succinate, malate or ascorbate occurred, neither did it with these substrates in the presence of ATP under anaerobic conditions, suggesting that there was no energy-conserving site between NADH and cytochrome b. 6. Succinate oxidation, in contrast with that of NADH and ascorbate, was strongly inhibited by uncouplers and stimulated by ATP hydrolysis. These effects were not observed when phenazine methosulphate, which transfers electrons from succinate dehydrogenase directly to oxygen, was present. It was concluded that in these vesicles the oxidation of succinate was energy-dependent and that the reoxidation of reduced succinate dehydrogenase was dependent on the outward movement of H(+) by the protonmotive force. 7. In support of the foregoing conclusion it was shown that the reduction of fumarate by NADH was an energy-conserving process. 8. If the activities of vesicles accurately represent those of the intact organism it appears that in B. caldolyticus the reduction of fumarate to succinate at the expense of reducing equivalents from NADH is energetically favoured over succinate oxidation even under aerobic conditions. This may be related to the need for an ample supply of succinate for haem synthesis in order to provide cytochromes for the organism."}
{"id": "PMID:205223", "title": "Hyporesponsiveness of lymphocytes to virus antigens in rheumatoid arthritis.", "content": "The immune response of peripheral blood lymphocytes to measles, rubella, parainfluenza types 1, 2, and 3 RNA virus antigens and to varicella-zoster and herpes virus type 1 DNA virus antigens was evaluated in 14 patients with rheumatoid arthritis (RA) and 14 matched controls by assessing 3H-thymidine incorporation. The results demonstrated hyporesponsivenss of lymphocytes from RA patients to virus antigens and phytohemagglutinin (PHA), which did not appear to be nonspecific because of a lack of correlation between response to virus antigens and response to mitogens. The patterns of decreased responsiveness was suggestive of a relative restriction of hyporesponsiveness to RNA virus antigens.", "contents": "Hyporesponsiveness of lymphocytes to virus antigens in rheumatoid arthritis. The immune response of peripheral blood lymphocytes to measles, rubella, parainfluenza types 1, 2, and 3 RNA virus antigens and to varicella-zoster and herpes virus type 1 DNA virus antigens was evaluated in 14 patients with rheumatoid arthritis (RA) and 14 matched controls by assessing 3H-thymidine incorporation. The results demonstrated hyporesponsivenss of lymphocytes from RA patients to virus antigens and phytohemagglutinin (PHA), which did not appear to be nonspecific because of a lack of correlation between response to virus antigens and response to mitogens. The patterns of decreased responsiveness was suggestive of a relative restriction of hyporesponsiveness to RNA virus antigens."}
{"id": "PMID:205224", "title": "Immunopathologic studies of rheumatoid arthritis. I. Absence of complement-dependent cytotoxicity of rheumatoid sera for rheumatoid synovial cell cultures.", "content": "A sensitive complement-dependent chromium release cytotoxicity assay was used to determine whether sera from rheumatoid arthritis (RA) patients contain antibody specific for an antigen on rheumatoid synovial cell cultures. Two hundred eight RA sera-RA synovial culture combinations were studied employing 21 sera and 16 synovial membranes; control combinations were derived from 5 normal sera and 10 degenerative joint disease synovial membranes. Anticomplementary activity of some rheumatoid sera was overcome using an increased complement concentration. The percent cytotoxicity of RA serum-RA culture combinations, both homologous and autologous, was not significantly greater than that of RA serum-control culture combinations. No correlation between duration of disease or duration of cell culture and percent cytotoxicity was found. Thus a unique antigen on cultured rheumatoid synovial cells was not recognized by rheumatoid serum antibody by use of this cytotoxicity assay.", "contents": "Immunopathologic studies of rheumatoid arthritis. I. Absence of complement-dependent cytotoxicity of rheumatoid sera for rheumatoid synovial cell cultures. A sensitive complement-dependent chromium release cytotoxicity assay was used to determine whether sera from rheumatoid arthritis (RA) patients contain antibody specific for an antigen on rheumatoid synovial cell cultures. Two hundred eight RA sera-RA synovial culture combinations were studied employing 21 sera and 16 synovial membranes; control combinations were derived from 5 normal sera and 10 degenerative joint disease synovial membranes. Anticomplementary activity of some rheumatoid sera was overcome using an increased complement concentration. The percent cytotoxicity of RA serum-RA culture combinations, both homologous and autologous, was not significantly greater than that of RA serum-control culture combinations. No correlation between duration of disease or duration of cell culture and percent cytotoxicity was found. Thus a unique antigen on cultured rheumatoid synovial cells was not recognized by rheumatoid serum antibody by use of this cytotoxicity assay."}
{"id": "PMID:205226", "title": "[Enhanced bioavailability of digoxin from silica matrix formulations (author's transl)].", "content": "The bioavailability of digoxin from 3 silica matrix formulations was assessed in single-dose crossover studies in 12 healthy human volunteers: digoxin/silica matrix tablets (I, Digacin), digoxin/silica matrix in capsule form (II) and digoxin/silica matrix drag\u00e9es, protected against gastrict juice by film coating (III). Urinary glycoside excretion for 6 days after 0.5 mg doses were measured by radioimmunoasay. Referring to an intravenous injection the bioavailability of digoxin from Digacin tablets is 82%, from the encapsulated matrix 69%, and from the drag\u00e9es 54%. In comparison with corresponding results from other investigators Digacin tablets havet the same high bioavailability as digoxin solutions. In vitro liberations of digoxin from the silica matrix formulations (94% in 90 s) is significantly better than from conventional tablets produces from a digoxin-lactose trituration (61% in 90 s).", "contents": "[Enhanced bioavailability of digoxin from silica matrix formulations (author's transl)]. The bioavailability of digoxin from 3 silica matrix formulations was assessed in single-dose crossover studies in 12 healthy human volunteers: digoxin/silica matrix tablets (I, Digacin), digoxin/silica matrix in capsule form (II) and digoxin/silica matrix drag\u00e9es, protected against gastrict juice by film coating (III). Urinary glycoside excretion for 6 days after 0.5 mg doses were measured by radioimmunoasay. Referring to an intravenous injection the bioavailability of digoxin from Digacin tablets is 82%, from the encapsulated matrix 69%, and from the drag\u00e9es 54%. In comparison with corresponding results from other investigators Digacin tablets havet the same high bioavailability as digoxin solutions. In vitro liberations of digoxin from the silica matrix formulations (94% in 90 s) is significantly better than from conventional tablets produces from a digoxin-lactose trituration (61% in 90 s)."}
{"id": "PMID:205231", "title": "Tobramycin and neuromuscular transmission in the rat isolated phrenic nerve-diaphragm preparation.", "content": "The effects of different concentrations of tobramycin, streptomycin, neomycin and gentamicin on the rat isolated phrenic nerve-diaphragm preparation are reported. Streptomycin, neomycin and gentamicin produced dose-dependent neuromuscular blockade. Tobramycin increased the muscle response at high concentrations (6.4 X 10(-4) - 2.6 X 10(-2) mol litre-1, but had no detectable effect when used in therapeutically recommended concentrations.", "contents": "Tobramycin and neuromuscular transmission in the rat isolated phrenic nerve-diaphragm preparation. The effects of different concentrations of tobramycin, streptomycin, neomycin and gentamicin on the rat isolated phrenic nerve-diaphragm preparation are reported. Streptomycin, neomycin and gentamicin produced dose-dependent neuromuscular blockade. Tobramycin increased the muscle response at high concentrations (6.4 X 10(-4) - 2.6 X 10(-2) mol litre-1, but had no detectable effect when used in therapeutically recommended concentrations."}
{"id": "PMID:205232", "title": "Factors affecting serum IgA antibody to Epstein-Barr viral capsid antigens in nasopharyngeal carcinoma.", "content": "Irrespective of the ethnic origin of the patient, nasopharyngeal carcinoma (NPC), appears to stimulate the production of IgA antibodies against VCA. These antibodies are detected at high frequency and titres in sera from NPC patients but only rarely from control subjects. A majority of relapse-free survivors tested 1-12 years after radiotherapy (RT) sustain a detectable level of IgA anti-VCA. Serum titres of IgA anti-VCA remain relatively unchaged in individual NPC patients after RT, regardless of the disease evolution. These antibodies were detected in serum from one individual 9 months before NPC and the titre rose concomitantly with its clinical onset. Titres of IgA anti-VCA in multiple serum specimens from individual NPC patients, and in sera from different NPC patients, do not correlate with titres of IgG anti-VCA or with Serum IgA. It thus seems possible that the IgA anti-VCA in the sera of NPC patients might be largely derived near NPC. Apparently healthy individuals showing detectable IgA anti-VCA tend to aggregate in families of NPC patients. The distribution of siblings of these families who have the IgA anti-VCA reaction shows the binomial distribution expected for an autosomal recessive trait, implying the involvement of an autosomal recessive gene in the IgA anti-VCA response.", "contents": "Factors affecting serum IgA antibody to Epstein-Barr viral capsid antigens in nasopharyngeal carcinoma. Irrespective of the ethnic origin of the patient, nasopharyngeal carcinoma (NPC), appears to stimulate the production of IgA antibodies against VCA. These antibodies are detected at high frequency and titres in sera from NPC patients but only rarely from control subjects. A majority of relapse-free survivors tested 1-12 years after radiotherapy (RT) sustain a detectable level of IgA anti-VCA. Serum titres of IgA anti-VCA remain relatively unchaged in individual NPC patients after RT, regardless of the disease evolution. These antibodies were detected in serum from one individual 9 months before NPC and the titre rose concomitantly with its clinical onset. Titres of IgA anti-VCA in multiple serum specimens from individual NPC patients, and in sera from different NPC patients, do not correlate with titres of IgG anti-VCA or with Serum IgA. It thus seems possible that the IgA anti-VCA in the sera of NPC patients might be largely derived near NPC. Apparently healthy individuals showing detectable IgA anti-VCA tend to aggregate in families of NPC patients. The distribution of siblings of these families who have the IgA anti-VCA reaction shows the binomial distribution expected for an autosomal recessive trait, implying the involvement of an autosomal recessive gene in the IgA anti-VCA response."}
{"id": "PMID:205233", "title": "Cytotoxic effects of hexavalent and trivalent chromium on mammalian cells in vitro.", "content": "The cytotoxic effects of hexavalent (k(2)Cr(2)O(7)) and trivalent (CrCl(3)) chromium compounds have been studied in cultured hamster fibroblasts (BHK line) and human epithelial-like cells (HEp line).K(2)Cr(2)O(7) stimulates the uptake of labelled thymidine into the soluble intracellular pool (the stimulation of nucleoside uptake represents a specific effect of Cr(6+)) while Cr(3+) always exerts an inhibitory action. DNA Synthesis is inhibited by treatment with both chromium compounds, but especially by K(2)Cr(2)O(7). Moreover, the effective CrCl(3) concentrations reduce the sensitivity of DNA and RNA to hydrolysis with perchloric acid. Treatments with k(2)Cr(2)O(7) in balanced salt solution, where Cr(6+) reduction is less marked, induce more pronounced cytotoxic effects than treatments in complete growth medium.HEp cells turned out to be more sensitive to K(2)Cr(2)O(7) than BHK fibroblasts: in the former line TdR uptake is less stimulated, DNA synthesis and cell survival are more affected. Survival of BHK cells to K(2)Cr(2)O(7) indicates a multi-hit mechanism of cell inactivation, the extrapolation number being about 10.On the basis of quantitative Cr determinations in the treatment solutions and in the treated cells, the cytotoxic effects of Cr are attributed to the action of Cr(6+) at the plasma membrane level on the mechanisms involved in nucleoside uptake, and to the interaction of Cr(3+) at the intracellular level with nucleophilic targets on the DNA molecule.", "contents": "Cytotoxic effects of hexavalent and trivalent chromium on mammalian cells in vitro. The cytotoxic effects of hexavalent (k(2)Cr(2)O(7)) and trivalent (CrCl(3)) chromium compounds have been studied in cultured hamster fibroblasts (BHK line) and human epithelial-like cells (HEp line).K(2)Cr(2)O(7) stimulates the uptake of labelled thymidine into the soluble intracellular pool (the stimulation of nucleoside uptake represents a specific effect of Cr(6+)) while Cr(3+) always exerts an inhibitory action. DNA Synthesis is inhibited by treatment with both chromium compounds, but especially by K(2)Cr(2)O(7). Moreover, the effective CrCl(3) concentrations reduce the sensitivity of DNA and RNA to hydrolysis with perchloric acid. Treatments with k(2)Cr(2)O(7) in balanced salt solution, where Cr(6+) reduction is less marked, induce more pronounced cytotoxic effects than treatments in complete growth medium.HEp cells turned out to be more sensitive to K(2)Cr(2)O(7) than BHK fibroblasts: in the former line TdR uptake is less stimulated, DNA synthesis and cell survival are more affected. Survival of BHK cells to K(2)Cr(2)O(7) indicates a multi-hit mechanism of cell inactivation, the extrapolation number being about 10.On the basis of quantitative Cr determinations in the treatment solutions and in the treated cells, the cytotoxic effects of Cr are attributed to the action of Cr(6+) at the plasma membrane level on the mechanisms involved in nucleoside uptake, and to the interaction of Cr(3+) at the intracellular level with nucleophilic targets on the DNA molecule."}
{"id": "PMID:205234", "title": "Binding of microorganisms to the macrophage plasma membrane; effects of enzymes and periodate.", "content": "The nature of the binding of C. parvum organisms to the surface of glass-adherent mouse peritoneal exudate cells in vitro was studied using pretreatment of the cells with various enzymes and periodate. Trypsin, pronase, beta-galactosidase, phospholipases A, C and D and periodate all caused a decrease in binding to 40-60% of untreated control. Neuraminidase led to a 30% increase in binding. The binding ability returned to normal after 1 h at 37 degrees in culture medium following exposure to all the enzymes apart from pronase, which apparently could not be removed effectively by washing. The presence of EDTA in the medium inhibited recovery from treatment with trypsin and beta-galactosidase; return to normal after exposure to phospholipases A, C and D was slightly affected, whereas recovery from treatment with neuraminidase was unaffected. Cells that had been exposed to periodate did not regain normal binding ability after 1 h in tissue culture medium but the effect could be reversed chemically by treatment with borohydride. The role of different plasma membrane components in non-specific cellular recognition is discussed.", "contents": "Binding of microorganisms to the macrophage plasma membrane; effects of enzymes and periodate. The nature of the binding of C. parvum organisms to the surface of glass-adherent mouse peritoneal exudate cells in vitro was studied using pretreatment of the cells with various enzymes and periodate. Trypsin, pronase, beta-galactosidase, phospholipases A, C and D and periodate all caused a decrease in binding to 40-60% of untreated control. Neuraminidase led to a 30% increase in binding. The binding ability returned to normal after 1 h at 37 degrees in culture medium following exposure to all the enzymes apart from pronase, which apparently could not be removed effectively by washing. The presence of EDTA in the medium inhibited recovery from treatment with trypsin and beta-galactosidase; return to normal after exposure to phospholipases A, C and D was slightly affected, whereas recovery from treatment with neuraminidase was unaffected. Cells that had been exposed to periodate did not regain normal binding ability after 1 h in tissue culture medium but the effect could be reversed chemically by treatment with borohydride. The role of different plasma membrane components in non-specific cellular recognition is discussed."}
{"id": "PMID:205235", "title": "The relationship between cyclic adenosine 3', 5' - monophosphate and biochemical events in rat skin after the induction of epidermal hyperplasia using hexadecane.", "content": "Sequential changes in skin metabolism have been studied in a model system of epidermal hyperplasia and hyperkeratinization induced by the application of n-hexadecane to shaved rat skin. The epidermal accumulation of glycogen typical of the hyperplastic response has been correlated with an increase in glycogenesis and a decrease in glycogenolysis. DNA synthesis was increased by 6 h after the start of hexadecane treatment and reached a maximum after one day. The concentration of skin cyclic AMP fell immediately after hexadecane application and subsequently rose to give a prolonged increase. Use of the combined topical application of hexadecane and the anti-inflammatory drugs triamcinolone acetonide, hydrocortisone and indomethacin showed that the hexadecane-induced changes in DNA synthesis and glycogen metabolism were linked to the initial fall in cyclic AMP concentration. The significance of the biphasic change in cyclic AMP levels is discussed as a possible system of control for the development and maintenance of hyperplasia.", "contents": "The relationship between cyclic adenosine 3', 5' - monophosphate and biochemical events in rat skin after the induction of epidermal hyperplasia using hexadecane. Sequential changes in skin metabolism have been studied in a model system of epidermal hyperplasia and hyperkeratinization induced by the application of n-hexadecane to shaved rat skin. The epidermal accumulation of glycogen typical of the hyperplastic response has been correlated with an increase in glycogenesis and a decrease in glycogenolysis. DNA synthesis was increased by 6 h after the start of hexadecane treatment and reached a maximum after one day. The concentration of skin cyclic AMP fell immediately after hexadecane application and subsequently rose to give a prolonged increase. Use of the combined topical application of hexadecane and the anti-inflammatory drugs triamcinolone acetonide, hydrocortisone and indomethacin showed that the hexadecane-induced changes in DNA synthesis and glycogen metabolism were linked to the initial fall in cyclic AMP concentration. The significance of the biphasic change in cyclic AMP levels is discussed as a possible system of control for the development and maintenance of hyperplasia."}
{"id": "PMID:205236", "title": "Distribution of enzyme of nucleic acid metabolism in cow snout epidermis.", "content": "Certain enzymes participating in the degradation of DNA have been measured in cow snout epidermis, liver, kidney and intestinal epithelium. High activities were found in epidermis compared to other tissues. The enzyme profile of the epidermis was investigated in relation to depth. Those enzymes directly concerned with DNA degradation occurred mainly in the upper (keratinizing) layer.", "contents": "Distribution of enzyme of nucleic acid metabolism in cow snout epidermis. Certain enzymes participating in the degradation of DNA have been measured in cow snout epidermis, liver, kidney and intestinal epithelium. High activities were found in epidermis compared to other tissues. The enzyme profile of the epidermis was investigated in relation to depth. Those enzymes directly concerned with DNA degradation occurred mainly in the upper (keratinizing) layer."}
{"id": "PMID:205237", "title": "Some features of bone marrow macrophages in patients with homozygous beta-thalassaemia.", "content": "The bone marrow macrophages of patients with homozygous beta-thalassaemia were frequently situated adjacent to collagen fibres and sometimes formed intrasinusoidal cytoplasmic protrusions. They also appeared to phagocytose processes of erythroblast cytoplasm (at times containing precipitated alpha-chains) which projected into them from neighbouring erythroblasts. The cytoplasm of the macrophages included large numbers of heavily-iron-loaded secondary lysosomes of various sizes and shapes in addition to phagocytosed erythroblasts, erythrocytes and extruded erythroblast nuclei. Numerous ferritin molecules were found in the cytoplasmic matrix but there were hardly any in the mitochondria, endoplasmic reticulum or golgi saccules. A small number of ferritin molecules were present within the nucleus. Electron microscope autoradiographs of marrow fragments which had been incubated with [3H]leucine for 1 h revealed the presence of newly-synthesized protein molecules in all types of secondary lysosomes. Light microscope autoradiographs showed the [3H]thymidine labelling index of the bone marrow macrophages was less than 1% and suggested that only a very small proportion of these cells were actively preparing for division.", "contents": "Some features of bone marrow macrophages in patients with homozygous beta-thalassaemia. The bone marrow macrophages of patients with homozygous beta-thalassaemia were frequently situated adjacent to collagen fibres and sometimes formed intrasinusoidal cytoplasmic protrusions. They also appeared to phagocytose processes of erythroblast cytoplasm (at times containing precipitated alpha-chains) which projected into them from neighbouring erythroblasts. The cytoplasm of the macrophages included large numbers of heavily-iron-loaded secondary lysosomes of various sizes and shapes in addition to phagocytosed erythroblasts, erythrocytes and extruded erythroblast nuclei. Numerous ferritin molecules were found in the cytoplasmic matrix but there were hardly any in the mitochondria, endoplasmic reticulum or golgi saccules. A small number of ferritin molecules were present within the nucleus. Electron microscope autoradiographs of marrow fragments which had been incubated with [3H]leucine for 1 h revealed the presence of newly-synthesized protein molecules in all types of secondary lysosomes. Light microscope autoradiographs showed the [3H]thymidine labelling index of the bone marrow macrophages was less than 1% and suggested that only a very small proportion of these cells were actively preparing for division."}
{"id": "PMID:205238", "title": "Impairment of platelet thromboxane A2 generation and of the platelet release reaction in two patients with congenital deficiency of platelet cyclo-oxygenase.", "content": "Two cases of thrombocytopathia with congenital deficiency of platelet cyclo-oxygenase were investigated. The platelet release reaction was impaired. There was a marked decrease of aggregation with collagen and with adrenalin and a total absence of aggregation with sodium arachidonate. The platelet response to labile aggregation stimulating substance (LASS, mostly thromboxane A2) was normal. There was no biosynthesis of prostaglandin cyclic endoperoxides or of thromboxane A2 from arachidonic acid. Basal levels of platelet PGE1 were lowered although plasma levels were normal. Thrombin decreased the cyclic AMP content of patients' platelets and also that of control platelets pretreated with aspirin. The patients platelets showed no ultrastructural difference when compared with control platelets, except for a slight decrease of granule volume, but, in contrast to control platelets, thrombin (0.02 U/ml) did not provoke contraction of the patients' platelets.", "contents": "Impairment of platelet thromboxane A2 generation and of the platelet release reaction in two patients with congenital deficiency of platelet cyclo-oxygenase. Two cases of thrombocytopathia with congenital deficiency of platelet cyclo-oxygenase were investigated. The platelet release reaction was impaired. There was a marked decrease of aggregation with collagen and with adrenalin and a total absence of aggregation with sodium arachidonate. The platelet response to labile aggregation stimulating substance (LASS, mostly thromboxane A2) was normal. There was no biosynthesis of prostaglandin cyclic endoperoxides or of thromboxane A2 from arachidonic acid. Basal levels of platelet PGE1 were lowered although plasma levels were normal. Thrombin decreased the cyclic AMP content of patients' platelets and also that of control platelets pretreated with aspirin. The patients platelets showed no ultrastructural difference when compared with control platelets, except for a slight decrease of granule volume, but, in contrast to control platelets, thrombin (0.02 U/ml) did not provoke contraction of the patients' platelets."}
{"id": "PMID:205239", "title": "Intracellular lambda light chain inclusions in chronic lymphocytic leukaemia.", "content": "A case of chronic lymphocytic leukaemia (CLL) with intracytoplasmic crystalline inclusions in peripheral blood lymphocytes is presented. The inclusions were identified as crystals of lambda (lambda) light chain and were present in bone marrow derived (B-cells) lymphocytes. The occurrence of light chain crystals in CLL may reflect a more primitive defect in immunoglobulin (Ig) synthesis, intracellular transport or secretion than has previously been reported.", "contents": "Intracellular lambda light chain inclusions in chronic lymphocytic leukaemia. A case of chronic lymphocytic leukaemia (CLL) with intracytoplasmic crystalline inclusions in peripheral blood lymphocytes is presented. The inclusions were identified as crystals of lambda (lambda) light chain and were present in bone marrow derived (B-cells) lymphocytes. The occurrence of light chain crystals in CLL may reflect a more primitive defect in immunoglobulin (Ig) synthesis, intracellular transport or secretion than has previously been reported."}
{"id": "PMID:205240", "title": "The orientation of a heme of cytochrome c oxidase in submitochondrial particles.", "content": "The electron paramagnetic resonance of the low spin signal from oxidized cytochrome c oxidase has been studied in oreinted multilayers of submitochondrial and electron transport particles. Measurements of the angular variation of the EPR spectra with the multilayer plane orientation allow the determination of the heme orientation in the multilayer. The heme normal lies in the membrane plane and the y-axis of the heme makes an angle of 30 degrees with the membrane normal. Analysis of the line shape reveals the presence of mosaic spread in the multilayer almost half of which is attributable to deviations of protein orientation within the membrane.", "contents": "The orientation of a heme of cytochrome c oxidase in submitochondrial particles. The electron paramagnetic resonance of the low spin signal from oxidized cytochrome c oxidase has been studied in oreinted multilayers of submitochondrial and electron transport particles. Measurements of the angular variation of the EPR spectra with the multilayer plane orientation allow the determination of the heme orientation in the multilayer. The heme normal lies in the membrane plane and the y-axis of the heme makes an angle of 30 degrees with the membrane normal. Analysis of the line shape reveals the presence of mosaic spread in the multilayer almost half of which is attributable to deviations of protein orientation within the membrane."}
{"id": "PMID:205241", "title": "Theory of proton hyperfine interactions in bacterial photosynthetic systems. Bacteriopheophytin cation and anion.", "content": "The electronic structures of the cation and anion of bacteriopheophytin alpha monomer are investigated by the self-consistent charge extended H\u00fcckel procedure including both pi and sigma electrons in the molecule. The calculated electron distributions are tested by comparison of the predicted hyperfine fields at proton sites with experimental data in both the ions and most important, by their ability to explain the observed trend in the hyperfine fields in going from the cation bacteriopheophytin+ alpha to the anion, a trend that is similar in many respects to the corresponding observed trend for the bacteriochlorophyll alpha cation and anion. Good agreement is obtained with experiment both for the absolute values of the observed proton hyperfine fields in both bacteriopheophytin a cation and anion as well as the ratio of the corresponding fields for the two systems. In particular, our calculated electron distributions in the two molecules lead, for the cation, to substantially different proton hyperfine fields for the two methyl groups attached to rings I and III, while for the anion, the corresponding fields are much closer to each other, a trend in good agreement with recent data. Also explained are the features of larger methine hyperfine constants in the anion as compared to the cation and the reverse trend for the protons in rings II and IV. Other features of the calculated electron distributions in the cation and anion are discussed and compared with each other. Possible additional measurements in the two systems that could provide further tests of the theoretically obtained electron distribution will be pointed out.", "contents": "Theory of proton hyperfine interactions in bacterial photosynthetic systems. Bacteriopheophytin cation and anion. The electronic structures of the cation and anion of bacteriopheophytin alpha monomer are investigated by the self-consistent charge extended H\u00fcckel procedure including both pi and sigma electrons in the molecule. The calculated electron distributions are tested by comparison of the predicted hyperfine fields at proton sites with experimental data in both the ions and most important, by their ability to explain the observed trend in the hyperfine fields in going from the cation bacteriopheophytin+ alpha to the anion, a trend that is similar in many respects to the corresponding observed trend for the bacteriochlorophyll alpha cation and anion. Good agreement is obtained with experiment both for the absolute values of the observed proton hyperfine fields in both bacteriopheophytin a cation and anion as well as the ratio of the corresponding fields for the two systems. In particular, our calculated electron distributions in the two molecules lead, for the cation, to substantially different proton hyperfine fields for the two methyl groups attached to rings I and III, while for the anion, the corresponding fields are much closer to each other, a trend in good agreement with recent data. Also explained are the features of larger methine hyperfine constants in the anion as compared to the cation and the reverse trend for the protons in rings II and IV. Other features of the calculated electron distributions in the cation and anion are discussed and compared with each other. Possible additional measurements in the two systems that could provide further tests of the theoretically obtained electron distribution will be pointed out."}
{"id": "PMID:205242", "title": "Resonance Raman spectra of cytochrome oxidase. Evidence for photoreduction by laser photons in resonance with the Soret band.", "content": "Resonance Raman spectra of cytochrome oxidase solubilized in Tween 20 and sodium cholate, and excited at 413.1 nm have been recorded. Differences in the resonance Raman spectra of the two preparations are minimal indicating that the local environment of the hemes is similar in the two preparations. As in the work of Salmeen, et al. (1973) (Biochem. Biophys. Res. Commun. 52, 1100) the strongest band appears at 1358 cm-1. Some of the other bands differ slightly in their band shapes and frequencies when compared to their spectra; these differences can be accounted for by differences in resonance enhancement of the various bands wnen exciting at 441.6 and 413.1 nm. A study of the region from 1350 to 1380 cm-1 as a function of laser intensity (10--130 mW on sample) indicate that the doublet reported by Salmeen, et al. at 1358 and 1372 cm-1 is a result of photoreduction of the preparations. In samples to which potassium ferricyanide had been added, broad luminescence bands appear at 476 and 641 nm from which it is inferred that catalytic amounts of flavin in the preparations are photoreduced providing reducing equivalents to cytochrome oxidase.", "contents": "Resonance Raman spectra of cytochrome oxidase. Evidence for photoreduction by laser photons in resonance with the Soret band. Resonance Raman spectra of cytochrome oxidase solubilized in Tween 20 and sodium cholate, and excited at 413.1 nm have been recorded. Differences in the resonance Raman spectra of the two preparations are minimal indicating that the local environment of the hemes is similar in the two preparations. As in the work of Salmeen, et al. (1973) (Biochem. Biophys. Res. Commun. 52, 1100) the strongest band appears at 1358 cm-1. Some of the other bands differ slightly in their band shapes and frequencies when compared to their spectra; these differences can be accounted for by differences in resonance enhancement of the various bands wnen exciting at 441.6 and 413.1 nm. A study of the region from 1350 to 1380 cm-1 as a function of laser intensity (10--130 mW on sample) indicate that the doublet reported by Salmeen, et al. at 1358 and 1372 cm-1 is a result of photoreduction of the preparations. In samples to which potassium ferricyanide had been added, broad luminescence bands appear at 476 and 641 nm from which it is inferred that catalytic amounts of flavin in the preparations are photoreduced providing reducing equivalents to cytochrome oxidase."}
{"id": "PMID:205243", "title": "Molecular motion and order in oriented lipid multibilayer membranes evaluated by simulations of spin label ESR spectra. Effects of temperature, cholesterol and magnetic field.", "content": "A simulation method to interpret electron spin resonance (ESR) of spin labelled amphiphilic molecules in oriented phosphatidylcholine multibilayers in terms of a restricted motional model is presented. Order and motion of the cholestane spin label (3-spiro-doxyl-5alpha-cholestane) incorporated into egg yolk phosphatidylcholine, dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine, pure and in mixture with cholesterol, were studied at various temperatures. With egg yolk phosphatidylcholine identical sets of motional parameters were obtained from simulations of ESR spectra obtained at three microwave frequencies (X-, K- and Q-band). With dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine analyses of the spectra show that phase transitions occur in samples containing up to 30 mol % cholesterol. The activation energy for the motion of the spin label is about three times larger above than below the phase transition, indicating a more collective motion in the lipid crystalline state than in the gel state. In the liquid crystalline state the activation energy is larger in the pure phosphatidylcholines than with cholesterol added. Additions of cholesterol to egg phosphatidylcholine induces a higher molecular order but does not appreciably affect correlation times. This is in contrast to dipalmitoylphosphatidylcholine where both order and correlation times are affected by the presence of cholesterol. The activation energies follow the same order as the transition temperatures: dipalmitoylphosphatidylcholine greater than dimyristoylphosphatidylcholine greater than egg yokd phosphatidylcholine, suggesting a similar order of the cooperativity of the motion of the lipid molecules. Magnetic field-induced effects on egg phosphatidylcholine multibilayers were found at Q-band measurements above 40 degrees C. The cholestane spin label mimics order and motion of cholesterol molecule incorporated into the lipid bilayers. This reflects order and motion of the portions of the lipid molecules on the same depth of the bilayer as the rigid steroid portions of the intercalated molecules.", "contents": "Molecular motion and order in oriented lipid multibilayer membranes evaluated by simulations of spin label ESR spectra. Effects of temperature, cholesterol and magnetic field. A simulation method to interpret electron spin resonance (ESR) of spin labelled amphiphilic molecules in oriented phosphatidylcholine multibilayers in terms of a restricted motional model is presented. Order and motion of the cholestane spin label (3-spiro-doxyl-5alpha-cholestane) incorporated into egg yolk phosphatidylcholine, dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine, pure and in mixture with cholesterol, were studied at various temperatures. With egg yolk phosphatidylcholine identical sets of motional parameters were obtained from simulations of ESR spectra obtained at three microwave frequencies (X-, K- and Q-band). With dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine analyses of the spectra show that phase transitions occur in samples containing up to 30 mol % cholesterol. The activation energy for the motion of the spin label is about three times larger above than below the phase transition, indicating a more collective motion in the lipid crystalline state than in the gel state. In the liquid crystalline state the activation energy is larger in the pure phosphatidylcholines than with cholesterol added. Additions of cholesterol to egg phosphatidylcholine induces a higher molecular order but does not appreciably affect correlation times. This is in contrast to dipalmitoylphosphatidylcholine where both order and correlation times are affected by the presence of cholesterol. The activation energies follow the same order as the transition temperatures: dipalmitoylphosphatidylcholine greater than dimyristoylphosphatidylcholine greater than egg yokd phosphatidylcholine, suggesting a similar order of the cooperativity of the motion of the lipid molecules. Magnetic field-induced effects on egg phosphatidylcholine multibilayers were found at Q-band measurements above 40 degrees C. The cholestane spin label mimics order and motion of cholesterol molecule incorporated into the lipid bilayers. This reflects order and motion of the portions of the lipid molecules on the same depth of the bilayer as the rigid steroid portions of the intercalated molecules."}
{"id": "PMID:205244", "title": "Chemically-induced cation permeability in red cell membrane vesicles. The sidedness of the response and the proteins involved.", "content": "Cation fluxes were measured in right-side-out and inside-out vesicles obtained from human red cells. Rubidium, which is spontaneously released at very slow rates, can be rapidly released from both types of vesicle by addition  of valinomycin. P-Chloromercuriphenyl sulfonic acid (PCMBS) also increases the cation permeability of the vesicles with reversal to normal after addition of dithiothreitol. The effect of PCMBS is considerably larger and appears faster in the inside-out vesicles as compared to the right-side-out vesicles, the difference being greater at low temperatures. These data indicate that the SH groups responsible for the changes in cation permeability are more accessible from the inside face of the membrane. The response to PCMBS was not diminished after selective removal of extrinsic proteins by alkaline extraction, and/or after the membranes were exposed to proteolytic enzymes. The major polypeptide component remaining in vesicles after both treatments was a 17 000-dalton transmembrane fragment derived from band 3 which might, therefore, be responsible for the permeability response. Addition of Ca2+ to either right-side-out or inside-out vesicles, in the presence or absence of ionophore A23187, was without effect on monovalent cation permeability, indicating that the mechanism of Ca2+-induced K+ permeation was lost or inactivated during the preparation of the vesicles.", "contents": "Chemically-induced cation permeability in red cell membrane vesicles. The sidedness of the response and the proteins involved. Cation fluxes were measured in right-side-out and inside-out vesicles obtained from human red cells. Rubidium, which is spontaneously released at very slow rates, can be rapidly released from both types of vesicle by addition  of valinomycin. P-Chloromercuriphenyl sulfonic acid (PCMBS) also increases the cation permeability of the vesicles with reversal to normal after addition of dithiothreitol. The effect of PCMBS is considerably larger and appears faster in the inside-out vesicles as compared to the right-side-out vesicles, the difference being greater at low temperatures. These data indicate that the SH groups responsible for the changes in cation permeability are more accessible from the inside face of the membrane. The response to PCMBS was not diminished after selective removal of extrinsic proteins by alkaline extraction, and/or after the membranes were exposed to proteolytic enzymes. The major polypeptide component remaining in vesicles after both treatments was a 17 000-dalton transmembrane fragment derived from band 3 which might, therefore, be responsible for the permeability response. Addition of Ca2+ to either right-side-out or inside-out vesicles, in the presence or absence of ionophore A23187, was without effect on monovalent cation permeability, indicating that the mechanism of Ca2+-induced K+ permeation was lost or inactivated during the preparation of the vesicles."}
{"id": "PMID:205245", "title": "Plasma membrane protein kinase activity in normal and Rous sarcoma virus-transformed chick embryo fibroblasts.", "content": "A preliminary study has been carried out to investigate the effect of Rous sarcoma virus transformation on plasma membrane protein kinase activity in chick embryo fibroblasts. Enzyme activity was measured using an in vitro phosphorylation method employing [gamma-32P]ATP with isolated plasma membranes serving as the source of both protein kinase and protein substrate. In general, the enzymatic properties observed were similar to those of other known protein kinases. However, for maximal activity a marked dependence on high Mg2+ concentrations was noted. Evidence was obtained which showed that cyclic nucleotide-dependent protein kinases were present in membranes from normal cells, but none could be measured in preparations from transformed cells. In addition, transformation appeared to result in a slight increase in basal plasma membrane protein kinase activity.", "contents": "Plasma membrane protein kinase activity in normal and Rous sarcoma virus-transformed chick embryo fibroblasts. A preliminary study has been carried out to investigate the effect of Rous sarcoma virus transformation on plasma membrane protein kinase activity in chick embryo fibroblasts. Enzyme activity was measured using an in vitro phosphorylation method employing [gamma-32P]ATP with isolated plasma membranes serving as the source of both protein kinase and protein substrate. In general, the enzymatic properties observed were similar to those of other known protein kinases. However, for maximal activity a marked dependence on high Mg2+ concentrations was noted. Evidence was obtained which showed that cyclic nucleotide-dependent protein kinases were present in membranes from normal cells, but none could be measured in preparations from transformed cells. In addition, transformation appeared to result in a slight increase in basal plasma membrane protein kinase activity."}
{"id": "PMID:205246", "title": "A calcium-activated polyphosphoinositide phosphodiesterase in the plasma membrane of human and rabbit erythrocytes.", "content": "Haemoglobin-free human erythrocyte ghosts that were prepared in the presence of EDTA and were then exposed to Ca2+ showed a substantial loss of phosphatidylinositol phosphate and phosphatidylinositol diphosphate, measured either chemically or by loss of 32P from the lipids of prelabelled membranes. At the same time there was, as reported previously (Allan, D. and Michell, R.H., (1976) Biochim. Biophys. Acta 455, 824--830), and approximately equivalent rise in the diacylglycerol content of the membranes. Analysis of the 32P-labelled water-soluble material released during this process showed that the major products were inositol diphosphate and inositol triphosphate. No change was seen in the phosphatidylinositol or phosphatidate content of the membranes, and there was no Ca2+-activated loss of 32P from the phosphatidate of prelabelled membranes: this suggests that Ca2+ did not activate phosphoinositide phosphomonoesterases or phosphatidate phosphomonoesterase in human erythrocyte membranes. It is concluded that human erythrocyte membranes contain at their cytoplasmic surface a Ca2+-activated phosphodiesterase that is active against both phosphatidylinositol phosphate and phosphatidylinositol diphosphate. Rabbit erythrocytes also contained this enzyme, but in these cells there was also evidence for the presence of a Ca2+-activated phosphatidate phosphomonoesterase.", "contents": "A calcium-activated polyphosphoinositide phosphodiesterase in the plasma membrane of human and rabbit erythrocytes. Haemoglobin-free human erythrocyte ghosts that were prepared in the presence of EDTA and were then exposed to Ca2+ showed a substantial loss of phosphatidylinositol phosphate and phosphatidylinositol diphosphate, measured either chemically or by loss of 32P from the lipids of prelabelled membranes. At the same time there was, as reported previously (Allan, D. and Michell, R.H., (1976) Biochim. Biophys. Acta 455, 824--830), and approximately equivalent rise in the diacylglycerol content of the membranes. Analysis of the 32P-labelled water-soluble material released during this process showed that the major products were inositol diphosphate and inositol triphosphate. No change was seen in the phosphatidylinositol or phosphatidate content of the membranes, and there was no Ca2+-activated loss of 32P from the phosphatidate of prelabelled membranes: this suggests that Ca2+ did not activate phosphoinositide phosphomonoesterases or phosphatidate phosphomonoesterase in human erythrocyte membranes. It is concluded that human erythrocyte membranes contain at their cytoplasmic surface a Ca2+-activated phosphodiesterase that is active against both phosphatidylinositol phosphate and phosphatidylinositol diphosphate. Rabbit erythrocytes also contained this enzyme, but in these cells there was also evidence for the presence of a Ca2+-activated phosphatidate phosphomonoesterase."}
{"id": "PMID:205247", "title": "Optimum interaction of sterol side chains with phosphatidylcholine.", "content": "The specificity of the interaction between the cholesterol side chain and egg phosphatidylcholine was precisely defined by examining the effect of three new analogues of cholesterol with modified side chains on the ordering of two steroid spin labels in liposomes. The complete side chain of cholesterol was shown to be required for maximum ordering. Sterols with side chains shorter or longer than cholesterol caused significantly less ordering.", "contents": "Optimum interaction of sterol side chains with phosphatidylcholine. The specificity of the interaction between the cholesterol side chain and egg phosphatidylcholine was precisely defined by examining the effect of three new analogues of cholesterol with modified side chains on the ordering of two steroid spin labels in liposomes. The complete side chain of cholesterol was shown to be required for maximum ordering. Sterols with side chains shorter or longer than cholesterol caused significantly less ordering."}
{"id": "PMID:205248", "title": "Specific release of plasma membrane enzymes by a phosphatidylinositol-specific phospholipase C.", "content": "The release of plasma membrane ecto-enzymes by a phosphatidylinositol-specific phospholipase C from Staphylococcus aureus was investigated. There was no effect on L-leucyl-beta-naphthylamidase, alkaline phosphodeisterase I and Ca2+- or MG2+-ATPase, but substantial proportions of the alkaline phosphatase and 5-nucleotidase were released. There was no simultaneous release of phospholipid and the solubilized enzymes were not exluded from Sepharose 6-B. It was therefore concluded that release was not a secondary consequence of membrane vesiculation but occurred as a result of the disruption of specific interactions involving the phosphatidylinositol molecule.", "contents": "Specific release of plasma membrane enzymes by a phosphatidylinositol-specific phospholipase C. The release of plasma membrane ecto-enzymes by a phosphatidylinositol-specific phospholipase C from Staphylococcus aureus was investigated. There was no effect on L-leucyl-beta-naphthylamidase, alkaline phosphodeisterase I and Ca2+- or MG2+-ATPase, but substantial proportions of the alkaline phosphatase and 5-nucleotidase were released. There was no simultaneous release of phospholipid and the solubilized enzymes were not exluded from Sepharose 6-B. It was therefore concluded that release was not a secondary consequence of membrane vesiculation but occurred as a result of the disruption of specific interactions involving the phosphatidylinositol molecule."}
{"id": "PMID:205249", "title": "The measurement of phosphatidate phosphohydrolase in human amniotic fluid.", "content": "Phosphatidate phosphohydrolase (EC 3.1.3.4) activity can be found in late gestational human amniotic fluid and is thought to originate in type II alveolar cells of the fetal lungs where it plays an important role in lung surfactant synthesis. In the present study, phosphatidate phosphohydrolase activity was detected and characterized in a 105 000 X g pellet of amniotic fluid using either [32P]phosphatidate or a water-soluble analog, 1-O-hexadecyl-rac-[2-(3)H]glycerol 3-phosphate as substrate. With either substrate, enzyme activity was optimal at pH 6.0. The soluble analog was hydrolyzed with a Km value of 163 micrometer and a V of 30 nmole/min per mg of protein, and offered several advantages over phosphatidate as a substrate for assaying phosphatidate phosphohydrolase in amniotic fluid. Using the synthetic analog, phosphatidate phosphohydrolase activity was measured in the 700 X g supernatant fraction of 30 human amniocentesis samples and compared with another index of fetal lung maturity, the phosphatidylcholine/sphingomyelin ratio. The results suggest that the new phosphohydrolase assay may be clinically useful in the assessment of fetal lung development.", "contents": "The measurement of phosphatidate phosphohydrolase in human amniotic fluid. Phosphatidate phosphohydrolase (EC 3.1.3.4) activity can be found in late gestational human amniotic fluid and is thought to originate in type II alveolar cells of the fetal lungs where it plays an important role in lung surfactant synthesis. In the present study, phosphatidate phosphohydrolase activity was detected and characterized in a 105 000 X g pellet of amniotic fluid using either [32P]phosphatidate or a water-soluble analog, 1-O-hexadecyl-rac-[2-(3)H]glycerol 3-phosphate as substrate. With either substrate, enzyme activity was optimal at pH 6.0. The soluble analog was hydrolyzed with a Km value of 163 micrometer and a V of 30 nmole/min per mg of protein, and offered several advantages over phosphatidate as a substrate for assaying phosphatidate phosphohydrolase in amniotic fluid. Using the synthetic analog, phosphatidate phosphohydrolase activity was measured in the 700 X g supernatant fraction of 30 human amniocentesis samples and compared with another index of fetal lung maturity, the phosphatidylcholine/sphingomyelin ratio. The results suggest that the new phosphohydrolase assay may be clinically useful in the assessment of fetal lung development."}
{"id": "PMID:205250", "title": "The effect of corticotropin on phospholipid metabolism in isolated adrenocortical cells.", "content": "Trypsin-dispersed cat adrenocortical cells were incubated at 37 degrees C in modified Eagle's medium containing [14C]arachidonic acid of sodium [14C]-acetate and then in non-radioactive medium. Radioactive incorporation was obtained in all phospholipids, with the greatest amount of radioactivity in phosphatidylcholine, followed by phosphatidylethanolamine, phosphatidyl-serine, and phosphatidylinositol. Concentrations of individual phospholipids generally paralleled the relative amounts of corresponding radiolabeled phospholipids, although the percentage of phosphatidylinositol was considerably lower than its radioactive counterpart, resulting in a high specific activity of this particular phospholipid. Although a potently steroidogenic concentration of corticotropin failed to enhance release of label from any particular phospholipid, analysis of specific activity showed that corticotropin stimulation was accompanied by an increased turnover of phosphatidylinositol and phosphatidic acid. These studies demonstrate that isolated cortical cells have the capacity to synthesize phospholipids from radioactive precursors. The finding that the acute effects of corticotropin are associated with changes in specific phospholipids, including phosphatidylinositol and phosphatidic acid, conforms to the general pattern observed in other secretory systems.", "contents": "The effect of corticotropin on phospholipid metabolism in isolated adrenocortical cells. Trypsin-dispersed cat adrenocortical cells were incubated at 37 degrees C in modified Eagle's medium containing [14C]arachidonic acid of sodium [14C]-acetate and then in non-radioactive medium. Radioactive incorporation was obtained in all phospholipids, with the greatest amount of radioactivity in phosphatidylcholine, followed by phosphatidylethanolamine, phosphatidyl-serine, and phosphatidylinositol. Concentrations of individual phospholipids generally paralleled the relative amounts of corresponding radiolabeled phospholipids, although the percentage of phosphatidylinositol was considerably lower than its radioactive counterpart, resulting in a high specific activity of this particular phospholipid. Although a potently steroidogenic concentration of corticotropin failed to enhance release of label from any particular phospholipid, analysis of specific activity showed that corticotropin stimulation was accompanied by an increased turnover of phosphatidylinositol and phosphatidic acid. These studies demonstrate that isolated cortical cells have the capacity to synthesize phospholipids from radioactive precursors. The finding that the acute effects of corticotropin are associated with changes in specific phospholipids, including phosphatidylinositol and phosphatidic acid, conforms to the general pattern observed in other secretory systems."}
{"id": "PMID:205251", "title": "Effects of ruthenium red, A23187 and D-600 on steroidogenesis in Y-1 cells.", "content": "The effects of the calcium antagonists ruthenium red and D-600 and the cation ionophore A23187 on steroidogenesis were investigated. Steroidogenesis triggered by corticotrophin and cyclic AMP was inhibited by each of the agents. Incubation of Y-1 cells with an excess of ethyleneglycol-bis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA) abolished the steroidogenic response to corticotrophin while the response to cyclic AMP was unaffected. The ability of ruthenium red and D-600 (1 . 10(-5) M), and A23187 (6 . 10(-6 M) to inhibit a response which does not require the presence of extracellular calcium (cyclic AMP induced steroidogenesis) suggests that they are altering intracellular calcium. Neither of the calcium antagonists nor the cation ionophore inhibited the steroidogenic response to exogenous pregnenolone, thereby suggesting that the cells were still viable. Only when A23187 was used in the presence of a 15-fold increase in extracellular calcium (4.8 mM) was the response to pregnenolone diminished. The data are interpreted as a further indication that, in intact cells, intracellular calcium plays a role in the steroidogenic pathway.", "contents": "Effects of ruthenium red, A23187 and D-600 on steroidogenesis in Y-1 cells. The effects of the calcium antagonists ruthenium red and D-600 and the cation ionophore A23187 on steroidogenesis were investigated. Steroidogenesis triggered by corticotrophin and cyclic AMP was inhibited by each of the agents. Incubation of Y-1 cells with an excess of ethyleneglycol-bis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA) abolished the steroidogenic response to corticotrophin while the response to cyclic AMP was unaffected. The ability of ruthenium red and D-600 (1 . 10(-5) M), and A23187 (6 . 10(-6 M) to inhibit a response which does not require the presence of extracellular calcium (cyclic AMP induced steroidogenesis) suggests that they are altering intracellular calcium. Neither of the calcium antagonists nor the cation ionophore inhibited the steroidogenic response to exogenous pregnenolone, thereby suggesting that the cells were still viable. Only when A23187 was used in the presence of a 15-fold increase in extracellular calcium (4.8 mM) was the response to pregnenolone diminished. The data are interpreted as a further indication that, in intact cells, intracellular calcium plays a role in the steroidogenic pathway."}
{"id": "PMID:205252", "title": "Regulation of cholesterol ester synthesis in cultured glial and neuronal cells. Relation to control of cholesterol synthesis.", "content": "Regulation of cholesterol ester synthesis was studied in cultured C-6 glial and neuroblastoma cells. Particular emphasis was placed on the relation of this regulation to control of cholesterol synthesis. The effectors studied were low density lipoprotein (LDL) and desmosterol. Distinct differences in regulation were observed between the glial and neuronal cells. In the neuronal cells cholesterol ester synthesis (from [14C]oleate) was not affected by even high concentrations of LDL or desmosterol. In contrast, cholesterol ester synthesis was stimulated as much as 12-fold in the glial cells after just 5 h exposure to LDL or desmosterol. Cholesterol synthesis (from [14C]acetate) was inhibited in a simultaneous and quantitatively similar manner. Suitable experiments indicated that alterations in pool sizes of intermediates did not contribute to the genesis of the observed responses and suggested that LDL and desmosterol produced their effects by stimulating esterification of primarily endogenous cholesterol. The data may have major implications concerning the controlling metabolic events prior to and at the onset of myelination.", "contents": "Regulation of cholesterol ester synthesis in cultured glial and neuronal cells. Relation to control of cholesterol synthesis. Regulation of cholesterol ester synthesis was studied in cultured C-6 glial and neuroblastoma cells. Particular emphasis was placed on the relation of this regulation to control of cholesterol synthesis. The effectors studied were low density lipoprotein (LDL) and desmosterol. Distinct differences in regulation were observed between the glial and neuronal cells. In the neuronal cells cholesterol ester synthesis (from [14C]oleate) was not affected by even high concentrations of LDL or desmosterol. In contrast, cholesterol ester synthesis was stimulated as much as 12-fold in the glial cells after just 5 h exposure to LDL or desmosterol. Cholesterol synthesis (from [14C]acetate) was inhibited in a simultaneous and quantitatively similar manner. Suitable experiments indicated that alterations in pool sizes of intermediates did not contribute to the genesis of the observed responses and suggested that LDL and desmosterol produced their effects by stimulating esterification of primarily endogenous cholesterol. The data may have major implications concerning the controlling metabolic events prior to and at the onset of myelination."}
{"id": "PMID:205253", "title": "Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and of incorporation of acetate into cholesterol in homozygous hypercholesterolemic fibroblasts by ferritin-low density lipoprotein conjugates.", "content": "Conjugates of ferritin with low density lipoproteins (LDL) were prepared and separated by sucrose gradient centrifugation. These conjugates, at cholesterol concentration of 100--132 microgram/ml, caused a greater than 90% suppression of hydroxymethylglutaryl coenzyme A reductase activity and of acetate incorporation into cholesterol in cultured skin fibroblasts from a normal subject as well as from a subject with homozygous familial hypercholesterolemia. The half maximal inhibition concentration was approx. 10 microgram/ml cholesterol for LDL and ferritin . (LDL)2 and 5 microgram/ml for (ferritin)2 . LDL in both cell lines. In contrast, native low density lipoproteins have only a minimal inhibitory effect in homozygous cells. The ability of the conjugates to stimulate the incorporation of oleate into cholesteryl esters was also equal in the two cell lines, although the conjugates were only 10% as active as low density lipoproteins in the normal cells. LDL reduced the ferritin . (LDL)2-mediated suppression of hydroxymethylglutaryl-CoA reductase activity in homozygous cells while ferritin . (LDL)2 reduced the LDL-mediated stimulation of cholesteryl ester formation in normal cells.", "contents": "Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and of incorporation of acetate into cholesterol in homozygous hypercholesterolemic fibroblasts by ferritin-low density lipoprotein conjugates. Conjugates of ferritin with low density lipoproteins (LDL) were prepared and separated by sucrose gradient centrifugation. These conjugates, at cholesterol concentration of 100--132 microgram/ml, caused a greater than 90% suppression of hydroxymethylglutaryl coenzyme A reductase activity and of acetate incorporation into cholesterol in cultured skin fibroblasts from a normal subject as well as from a subject with homozygous familial hypercholesterolemia. The half maximal inhibition concentration was approx. 10 microgram/ml cholesterol for LDL and ferritin . (LDL)2 and 5 microgram/ml for (ferritin)2 . LDL in both cell lines. In contrast, native low density lipoproteins have only a minimal inhibitory effect in homozygous cells. The ability of the conjugates to stimulate the incorporation of oleate into cholesteryl esters was also equal in the two cell lines, although the conjugates were only 10% as active as low density lipoproteins in the normal cells. LDL reduced the ferritin . (LDL)2-mediated suppression of hydroxymethylglutaryl-CoA reductase activity in homozygous cells while ferritin . (LDL)2 reduced the LDL-mediated stimulation of cholesteryl ester formation in normal cells."}
{"id": "PMID:205255", "title": "Proteolysis of very low density lipoprotein in perfused lung.", "content": "Perfusion of homologous 125I-labeled rat very low density lipoprotein through isolated rat lungs in the presence of heparin resulted in apoprotein proteolysis. At least the apoprotein C was degraded into two peptides smaller than 7500 daltons as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The lung uptake of radioactivity was small and due mainly to the presence of the larger of the two peptides. The lung protease was not active against an 125-I-labeled albumin substrate and was not released into the medium by heparin.", "contents": "Proteolysis of very low density lipoprotein in perfused lung. Perfusion of homologous 125I-labeled rat very low density lipoprotein through isolated rat lungs in the presence of heparin resulted in apoprotein proteolysis. At least the apoprotein C was degraded into two peptides smaller than 7500 daltons as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The lung uptake of radioactivity was small and due mainly to the presence of the larger of the two peptides. The lung protease was not active against an 125-I-labeled albumin substrate and was not released into the medium by heparin."}
{"id": "PMID:205256", "title": "Prostaglandin biosynthesis and catabolism in the lamb ductus arteriosus, aorta and pulmonary artery.", "content": "Homogenates of tissues from fetal and neonatal lamb ductus arteriosus, aorta and pulmonary artery have the capacity to convert arachidonic acid as well as the intermediate prostaglandin endoperoxide, prostaglandin H2, into three products: prostaglandins E2, F2alpha and a major product 6-ketoprostaglandin F1alpha. The three tissues also displayed prostaglandin 15-hydroxydehydrogenase and 13-reductase catabolic activities. The catabolishing system showed considerable substrate specificity: prostaglandin E1 was a good substrate whereas prostaglandins F1alpha and F2alpha were completely devoid of catabolism. The complete system was observed in immature as well as mature arterial vessels, in the fetus as well as the neonate (up to 7 days old). These experiments demonstrate the presence of several components of the prostaglandin system in these tissues and offer biochemical evidence for the implication of prostaglandins E2 and I2 in the maintenance of the ductus and neighboring vessels in a relaxed state in the fetus.", "contents": "Prostaglandin biosynthesis and catabolism in the lamb ductus arteriosus, aorta and pulmonary artery. Homogenates of tissues from fetal and neonatal lamb ductus arteriosus, aorta and pulmonary artery have the capacity to convert arachidonic acid as well as the intermediate prostaglandin endoperoxide, prostaglandin H2, into three products: prostaglandins E2, F2alpha and a major product 6-ketoprostaglandin F1alpha. The three tissues also displayed prostaglandin 15-hydroxydehydrogenase and 13-reductase catabolic activities. The catabolishing system showed considerable substrate specificity: prostaglandin E1 was a good substrate whereas prostaglandins F1alpha and F2alpha were completely devoid of catabolism. The complete system was observed in immature as well as mature arterial vessels, in the fetus as well as the neonate (up to 7 days old). These experiments demonstrate the presence of several components of the prostaglandin system in these tissues and offer biochemical evidence for the implication of prostaglandins E2 and I2 in the maintenance of the ductus and neighboring vessels in a relaxed state in the fetus."}
{"id": "PMID:205257", "title": "Induction of low density lipoprotein receptor synthesis by high density lipoprotein in cultures of human skin fibroblasts.", "content": "Further studies have been made of the effects of high density lipoprotein (HDL) on the surface binding, internalization and degradation of 125I-labeled low density lipoprotein (125I-labeled LDL) by cultured normal human fibroblasts. In agreement with earlier studies, during short incubations HDL inhibited the surface binding of 125I-labeled LDL. In contrast, following prolonged incubations 125I-labeled LDL binding was consistently greater in the presence of HDL. The increment in 125I-labeled LDL binding induced by HDL was: (a) associated with a decrease in cell cholesterol content; (b) inhibited by the addition of cholesterol or cycloheximide to the incubation medium; and (c) accompanied by similar increments in 125I-labeled LDL internalization and degradation. It is concluded that HDL induces the synthesis of high affinity LDL receptors in human fibroblasts by promoting the efflux of cholesterol from the cells.", "contents": "Induction of low density lipoprotein receptor synthesis by high density lipoprotein in cultures of human skin fibroblasts. Further studies have been made of the effects of high density lipoprotein (HDL) on the surface binding, internalization and degradation of 125I-labeled low density lipoprotein (125I-labeled LDL) by cultured normal human fibroblasts. In agreement with earlier studies, during short incubations HDL inhibited the surface binding of 125I-labeled LDL. In contrast, following prolonged incubations 125I-labeled LDL binding was consistently greater in the presence of HDL. The increment in 125I-labeled LDL binding induced by HDL was: (a) associated with a decrease in cell cholesterol content; (b) inhibited by the addition of cholesterol or cycloheximide to the incubation medium; and (c) accompanied by similar increments in 125I-labeled LDL internalization and degradation. It is concluded that HDL induces the synthesis of high affinity LDL receptors in human fibroblasts by promoting the efflux of cholesterol from the cells."}
{"id": "PMID:205259", "title": "Enhanced degradation of trypsin-treated low density lipoprotein by fibroblasts from a patient with homozygous familial hypercholesterolemia.", "content": "When 125I-labeled native low density lipoprotein was incubated with skin fibroblasts from a patient with homozygous familial hypercholesterolemia, the observed rate of degradation of the protein moiety was less than 5% the rate observed with normal fibroblasts, in agreement with previous studies. When the low density lipoprotein had been first treated with trypsin, with release of about 20% of the protein, its degradation by the patient's fibroblasts was markedly increased 8-20-fold. In contrast, the rate of degradation of the trypsin-treated lipoprotein by normal fibroblasts was, if anything, slightly reduced. In neither the normal cells nor the patient's cells was binding to the cell surface appreciably altered by trypsin treatment of the lipoprotein. Prior incubation with cholesterol and 7-ketocholesterol reduced binding of trypsin-treated low density lipoprotein to normal cells by 67% but did not affect its binding to the patient's cells. The results show that the structural modifications induced by trypsin do not interfere with binding of low density lipoprotein to its normal high affinity receptor nor its degradation by normal cells. However, the modified lipoprotein is much more readily internalized and degraded by cells from the patient with homozygous familial hypercholesterolemia.", "contents": "Enhanced degradation of trypsin-treated low density lipoprotein by fibroblasts from a patient with homozygous familial hypercholesterolemia. When 125I-labeled native low density lipoprotein was incubated with skin fibroblasts from a patient with homozygous familial hypercholesterolemia, the observed rate of degradation of the protein moiety was less than 5% the rate observed with normal fibroblasts, in agreement with previous studies. When the low density lipoprotein had been first treated with trypsin, with release of about 20% of the protein, its degradation by the patient's fibroblasts was markedly increased 8-20-fold. In contrast, the rate of degradation of the trypsin-treated lipoprotein by normal fibroblasts was, if anything, slightly reduced. In neither the normal cells nor the patient's cells was binding to the cell surface appreciably altered by trypsin treatment of the lipoprotein. Prior incubation with cholesterol and 7-ketocholesterol reduced binding of trypsin-treated low density lipoprotein to normal cells by 67% but did not affect its binding to the patient's cells. The results show that the structural modifications induced by trypsin do not interfere with binding of low density lipoprotein to its normal high affinity receptor nor its degradation by normal cells. However, the modified lipoprotein is much more readily internalized and degraded by cells from the patient with homozygous familial hypercholesterolemia."}
{"id": "PMID:205260", "title": "The effects of dibutyryl cyclic adenosine 3':5'-monophosphate on concanavalin A-stimulated sterol and fatty acid synthesis in mouse spleen lymphocytes.", "content": "Substantial increases in both 3beta-OH sterol and fatty acid synthesis were observed after concanavalin A addition to mouse spleen lymphocytes cultured in serum-free media. The rate of sterol synthesis increased linearly up to 60 h. The rate of fatty acid synthesis increased up to 20 h, reaching a plateau in synthetic activity which was the maintained. CO2 production from acetate was slightly stimulated by concanavalin A. In contrast to sterol and fatty acid synthesis, the rate of CO2 production in both mitogen-stimulated and resting cultures declined with time. Dibutyryl cyclic AMP had a strong inhibitory effect on concanavalin A-stimulated sterol and fatty acid synthesis from acetate, but only a slight effect on CO2 production. Delayed addition of dibutyryl cyclic AMP resulted in reduced inhibition. The data suggest a sequence of initiation for fatty acid and sterol synthesis prior to DNA synthesis and a possible regulatory role of cyclic AMP in this initiation. The results support the hypothesis that lymphocyte activation is sequential within the spleen cell population and is accompanied by fatty acid and sterol synthesis.", "contents": "The effects of dibutyryl cyclic adenosine 3':5'-monophosphate on concanavalin A-stimulated sterol and fatty acid synthesis in mouse spleen lymphocytes. Substantial increases in both 3beta-OH sterol and fatty acid synthesis were observed after concanavalin A addition to mouse spleen lymphocytes cultured in serum-free media. The rate of sterol synthesis increased linearly up to 60 h. The rate of fatty acid synthesis increased up to 20 h, reaching a plateau in synthetic activity which was the maintained. CO2 production from acetate was slightly stimulated by concanavalin A. In contrast to sterol and fatty acid synthesis, the rate of CO2 production in both mitogen-stimulated and resting cultures declined with time. Dibutyryl cyclic AMP had a strong inhibitory effect on concanavalin A-stimulated sterol and fatty acid synthesis from acetate, but only a slight effect on CO2 production. Delayed addition of dibutyryl cyclic AMP resulted in reduced inhibition. The data suggest a sequence of initiation for fatty acid and sterol synthesis prior to DNA synthesis and a possible regulatory role of cyclic AMP in this initiation. The results support the hypothesis that lymphocyte activation is sequential within the spleen cell population and is accompanied by fatty acid and sterol synthesis."}
{"id": "PMID:205261", "title": "Solubilization and separation of delta5,3beta-hydroxysteroid dehydrogenase and 3-oxosteroid-delta4-delta5-isomerase from bovine adrenal cortex microsomes.", "content": "A physical separation of delta5,3beta-hydroxysteroid dehydrogenase and 3-oxosteroid delta4-delta5-isomerase solubilized from bovine adrenocortical microsomes is described for the first time. The solubilization as well as the separation was carried out with a mixture of a detergent: a substituted betaine (Empigen BB/P) and sodium cholate. This latter detergent protects isomerase from complete inactivation by Empigen and is necessary for the recovery of a significant amount of soluble isomerase. Separation of dehydrogenase and isomerase was successfully accomplished by the use of a DEAE-Biogel A anion-exchanger. Dehydrogenase activity was eluted, while the isomerase was retained. Measurements of dehydrogenase activity with androst-5-en-3beta-ol-17-one, pregnen-3beta-ol-20-one and pregn-5-en-(3beta,17alpha)-diol-20-one and of isomerase activity with androst-5-en-(3,17)-dione and pregn-5-en-(3,20)-dione suggested that more than one isomerase and more than one dehydrogenase form were present.", "contents": "Solubilization and separation of delta5,3beta-hydroxysteroid dehydrogenase and 3-oxosteroid-delta4-delta5-isomerase from bovine adrenal cortex microsomes. A physical separation of delta5,3beta-hydroxysteroid dehydrogenase and 3-oxosteroid delta4-delta5-isomerase solubilized from bovine adrenocortical microsomes is described for the first time. The solubilization as well as the separation was carried out with a mixture of a detergent: a substituted betaine (Empigen BB/P) and sodium cholate. This latter detergent protects isomerase from complete inactivation by Empigen and is necessary for the recovery of a significant amount of soluble isomerase. Separation of dehydrogenase and isomerase was successfully accomplished by the use of a DEAE-Biogel A anion-exchanger. Dehydrogenase activity was eluted, while the isomerase was retained. Measurements of dehydrogenase activity with androst-5-en-3beta-ol-17-one, pregnen-3beta-ol-20-one and pregn-5-en-(3beta,17alpha)-diol-20-one and of isomerase activity with androst-5-en-(3,17)-dione and pregn-5-en-(3,20)-dione suggested that more than one isomerase and more than one dehydrogenase form were present."}
{"id": "PMID:205262", "title": "Comparative study on glycolipid composition between two cell types of rat ascites hepatoma cells.", "content": "A comparative study of the glycolipids was performed on two cell lines of rat ascites hepatomas, island-forming and free cell types, and several marked differences were found as follows: 1. Hexose content in glycolipids derived from AH 7974F (free cell type) was about 3.6-fold as much as that from AH 7974 (island-forming cell type) on the basis of dry cell weight. 2. The glycolipids in the cells of AH 7974 were tentatively identified as glucosylceramide, lactosylceramide, galactosylgalactosylglucosylceramide, globoside and hematoside (GM3) by both thin-layer and gas-liquid chromatography. 3. On the other hand, the glycolipids in AH 7974F cells were glucosylceramide, lactosylceramide and at least four unknown lipids. 4. Structure of one of these unknown lipids was shown to be asialo-GM2 by methylation and enzymatic degradation studies. Moreover, the presence of asialo-GM1 was suggested by immunoprecipitation test with anti-asialo-GM1 serum. 5. Glucosylceramide and lactosylceramide from AH 7974F cells were found to possess hydroxy fatty acids as major fatty acids components, which were rare in these glycolipids from AH 7974 cells.", "contents": "Comparative study on glycolipid composition between two cell types of rat ascites hepatoma cells. A comparative study of the glycolipids was performed on two cell lines of rat ascites hepatomas, island-forming and free cell types, and several marked differences were found as follows: 1. Hexose content in glycolipids derived from AH 7974F (free cell type) was about 3.6-fold as much as that from AH 7974 (island-forming cell type) on the basis of dry cell weight. 2. The glycolipids in the cells of AH 7974 were tentatively identified as glucosylceramide, lactosylceramide, galactosylgalactosylglucosylceramide, globoside and hematoside (GM3) by both thin-layer and gas-liquid chromatography. 3. On the other hand, the glycolipids in AH 7974F cells were glucosylceramide, lactosylceramide and at least four unknown lipids. 4. Structure of one of these unknown lipids was shown to be asialo-GM2 by methylation and enzymatic degradation studies. Moreover, the presence of asialo-GM1 was suggested by immunoprecipitation test with anti-asialo-GM1 serum. 5. Glucosylceramide and lactosylceramide from AH 7974F cells were found to possess hydroxy fatty acids as major fatty acids components, which were rare in these glycolipids from AH 7974 cells."}
{"id": "PMID:205263", "title": "A comparative spectroscopic study of two non-haem iron proteins lacking labile sulphide from Desulphovibrio gigas.", "content": "The ultraviolet visible, and near infrared spectrum of a two-iron protein from Desulphovibrio gigas, a new type of non-haem iron protein lacking labile sulphide, is compared with that of D. gigas rubredoxin. The charge transfer band maxima of rubredoxin at 495 and 565 nm are less separated in the new protein implying a higher symmetry of the two iron centres. The existence of a spin-spin interaction between the two iron centres in the new protein is suggested by the magnetic susceptibility measurements of the oxidized and reduced states of both proteins, which gives a smaller value per iron centre for the new protein. The oxidized form of the two iron-protein has a complex EPR spectrum with signals at g values of 8.97, 7.72, 5.73, 4.94, and 1.84. An EPR titration gives a value of --35 +/- 15 mV for the two signals at g values of 7.72 and 5.73. Rubredoxin has the characteristic spectrum of rubredoxins with two signals at g values of 9.4 and 4.27.", "contents": "A comparative spectroscopic study of two non-haem iron proteins lacking labile sulphide from Desulphovibrio gigas. The ultraviolet visible, and near infrared spectrum of a two-iron protein from Desulphovibrio gigas, a new type of non-haem iron protein lacking labile sulphide, is compared with that of D. gigas rubredoxin. The charge transfer band maxima of rubredoxin at 495 and 565 nm are less separated in the new protein implying a higher symmetry of the two iron centres. The existence of a spin-spin interaction between the two iron centres in the new protein is suggested by the magnetic susceptibility measurements of the oxidized and reduced states of both proteins, which gives a smaller value per iron centre for the new protein. The oxidized form of the two iron-protein has a complex EPR spectrum with signals at g values of 8.97, 7.72, 5.73, 4.94, and 1.84. An EPR titration gives a value of --35 +/- 15 mV for the two signals at g values of 7.72 and 5.73. Rubredoxin has the characteristic spectrum of rubredoxins with two signals at g values of 9.4 and 4.27."}
{"id": "PMID:205264", "title": "Oxygenation and EPR spectral properties of Aplysia myoglobins containing cobaltous porphyrins.", "content": "Cobalt myoglobins (Aplysia) have been reconstituted from apo-myoglobin (Aplysia) and proto-, meso-, and deutero-cobalt porphyrins. Each of them showed the 30--60 times lower oxygen affinity than those of the corresponding cobalt myoglobins (Sperm whale). Kinetic investigation of their oxygenation by the temperature-junp relaxation technique showed that the low oxygen affinity of cobalt myoglobin (Aplysia) is due to a large dissociation rate constant. the electron paramagnetic resonance (EPR) spectrum of oxy cobalt myoglobin (Aplysia) is affected by the replacement of H2O with D2O, suggesting a possible interaction between the bound oxygen and the neighboring hydrogen atom. A low temperature photodissociation study showed that the product of photolysis of oxy cobalt myoglobin (Aplysia) gives an EPR spectrum different from that of the deoxy-cobalt myoglobin (Aplysia) and from that of the photolysed form of oxy-cobalt myogloin (Sperm whale). These observations suggest that in oxy-cobalt myoglobin (Aplysia) the bound oxygen might interact with amino acid adjacent to it, but the interaction is weaker than that in oxy cobalt myoglobin (Sperm whale).", "contents": "Oxygenation and EPR spectral properties of Aplysia myoglobins containing cobaltous porphyrins. Cobalt myoglobins (Aplysia) have been reconstituted from apo-myoglobin (Aplysia) and proto-, meso-, and deutero-cobalt porphyrins. Each of them showed the 30--60 times lower oxygen affinity than those of the corresponding cobalt myoglobins (Sperm whale). Kinetic investigation of their oxygenation by the temperature-junp relaxation technique showed that the low oxygen affinity of cobalt myoglobin (Aplysia) is due to a large dissociation rate constant. the electron paramagnetic resonance (EPR) spectrum of oxy cobalt myoglobin (Aplysia) is affected by the replacement of H2O with D2O, suggesting a possible interaction between the bound oxygen and the neighboring hydrogen atom. A low temperature photodissociation study showed that the product of photolysis of oxy cobalt myoglobin (Aplysia) gives an EPR spectrum different from that of the deoxy-cobalt myoglobin (Aplysia) and from that of the photolysed form of oxy-cobalt myogloin (Sperm whale). These observations suggest that in oxy-cobalt myoglobin (Aplysia) the bound oxygen might interact with amino acid adjacent to it, but the interaction is weaker than that in oxy cobalt myoglobin (Sperm whale)."}
{"id": "PMID:205265", "title": "Assignment of the heme c resonances in the 360 MHz H NMR spectra of cytochrome c.", "content": "In the 360 MHz 1H NMR spectra of horse heart ferrocytochrome c recorded after suitable digital resolution enhancement, the resonances of all the heme c protons with the exception of those of the propionic acid side chains were observed as well resolved lines. From spin decoupling and nuclear Overhauser effects in homonuclear double resonance experiments, all these resonances were assigned to their respective positions in heme c. With saturation transfer experiments in solutions of partially reduced cytochrome c, individual assignments were further obtained for the six heme c methyl resonances in ferricytochrome c. The present experiments add individual assignments to the earlier identifications of the heme c ring methyl and meso-proton resonances, and show that the earlier identifications of the thioether bridge methyl resonances must be revised. These data provide a basis for more detailed descriptions of the electronic structure of heme c and its possible relations with the pathway of the electron transfer in and out of the cytochrome c molecule. Furthermore, the pseudocontact shifts of the thioether bridge methyl resonances could be related to the electronic g-tensor measured by EPR in ferricytochrome c single crystals at low temperature. From this it will now be possible without chemical modification of the protein, to compare in detail the solution conformations near the heme c in reduced and oxidized cytochrome c and thus hopefully to obtain additional insights into the mechanism of the biological redox reaction of this protein.", "contents": "Assignment of the heme c resonances in the 360 MHz H NMR spectra of cytochrome c. In the 360 MHz 1H NMR spectra of horse heart ferrocytochrome c recorded after suitable digital resolution enhancement, the resonances of all the heme c protons with the exception of those of the propionic acid side chains were observed as well resolved lines. From spin decoupling and nuclear Overhauser effects in homonuclear double resonance experiments, all these resonances were assigned to their respective positions in heme c. With saturation transfer experiments in solutions of partially reduced cytochrome c, individual assignments were further obtained for the six heme c methyl resonances in ferricytochrome c. The present experiments add individual assignments to the earlier identifications of the heme c ring methyl and meso-proton resonances, and show that the earlier identifications of the thioether bridge methyl resonances must be revised. These data provide a basis for more detailed descriptions of the electronic structure of heme c and its possible relations with the pathway of the electron transfer in and out of the cytochrome c molecule. Furthermore, the pseudocontact shifts of the thioether bridge methyl resonances could be related to the electronic g-tensor measured by EPR in ferricytochrome c single crystals at low temperature. From this it will now be possible without chemical modification of the protein, to compare in detail the solution conformations near the heme c in reduced and oxidized cytochrome c and thus hopefully to obtain additional insights into the mechanism of the biological redox reaction of this protein."}
{"id": "PMID:205266", "title": "Cleavage of native type III collagen in the collagenase susceptible region by thermolysin.", "content": "Viscometric assays were used to demonstrate the activity of thermolysin (EC 3.4.24.4) on native type III collagen in solution. Analysis of the reaction products by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and electron microscopic visualisation of segment long spacing aggregates demonstrated localised cleavage of the collagen in the collagenase susceptible region.", "contents": "Cleavage of native type III collagen in the collagenase susceptible region by thermolysin. Viscometric assays were used to demonstrate the activity of thermolysin (EC 3.4.24.4) on native type III collagen in solution. Analysis of the reaction products by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and electron microscopic visualisation of segment long spacing aggregates demonstrated localised cleavage of the collagen in the collagenase susceptible region."}
{"id": "PMID:205267", "title": "An adenosine 3':5'-monophosphate-adenosine binding protein from mouse liver: some physicochemical properties.", "content": "A number of physiochemical properties of the cyclic AMP-adenosine binding protein of mouse liver (Ueland, P.M. and D\u00f8skeland, S.O. (1977) J. Biol. Chem. 252, 677--686) have been studied. 1. The specific extinction coefficient, E1%280nm, was estimated to 13.0. 2. Amino acid and amide group analyses confirmed the acidic properties of the protein as determined by electrofocusing (pI = 5.7). Based on the estimated partial specific volume (v = 0.74 cm3/g) the minimum molecular weight of the native, tetrameric protein was recalculated to be 185 000 (s20,w = 8.8 . 10(-13) s and Stokes radius = 48 A). 3. No NH2-terminal amino acid was found by the dansyl method using [14C]-dansyl chloride, indicating that the NH2-terminal groups are blocked. 4. Amino acid analyses gave 6 half-cystine residues per subunit, and the same number of free sulfhydryl groups was found by titration of the denatured protein with 5,5'-dithiobis (2-nitrobenzoic acid). 5. The reactivity of the SH groups in the native protein with 5,5'-dithiobis (2-nitrobenzoic acid) revealed rapidly reacting (SHI), sluggishly reacting (SHII) and \"masked\" (SHIII) SH groups. ATP, adenosine, Mg2+ and KCl, factors known to affect the activation of cyclic AMP binding sites (Ueland, P.M. and D\u00f8skeland, S.O. (1978) Arch. Biochem. Biophys., in press) changed the reactivity of separate SH groups.", "contents": "An adenosine 3':5'-monophosphate-adenosine binding protein from mouse liver: some physicochemical properties. A number of physiochemical properties of the cyclic AMP-adenosine binding protein of mouse liver (Ueland, P.M. and D\u00f8skeland, S.O. (1977) J. Biol. Chem. 252, 677--686) have been studied. 1. The specific extinction coefficient, E1%280nm, was estimated to 13.0. 2. Amino acid and amide group analyses confirmed the acidic properties of the protein as determined by electrofocusing (pI = 5.7). Based on the estimated partial specific volume (v = 0.74 cm3/g) the minimum molecular weight of the native, tetrameric protein was recalculated to be 185 000 (s20,w = 8.8 . 10(-13) s and Stokes radius = 48 A). 3. No NH2-terminal amino acid was found by the dansyl method using [14C]-dansyl chloride, indicating that the NH2-terminal groups are blocked. 4. Amino acid analyses gave 6 half-cystine residues per subunit, and the same number of free sulfhydryl groups was found by titration of the denatured protein with 5,5'-dithiobis (2-nitrobenzoic acid). 5. The reactivity of the SH groups in the native protein with 5,5'-dithiobis (2-nitrobenzoic acid) revealed rapidly reacting (SHI), sluggishly reacting (SHII) and \"masked\" (SHIII) SH groups. ATP, adenosine, Mg2+ and KCl, factors known to affect the activation of cyclic AMP binding sites (Ueland, P.M. and D\u00f8skeland, S.O. (1978) Arch. Biochem. Biophys., in press) changed the reactivity of separate SH groups."}
{"id": "PMID:205268", "title": "Removal of nonionic detergent from proteins fractionated by electrofocusing.", "content": "The nonionic detergent Nonipol TD 12 (an alkyl polyoxyethylene alcohol) has been removed from solubilised proteins after their fractionation by electrofocusing. Following electrofocusing in nonionic detergent an anionic or cationic detergent was added to the focussing medium and the focusing was allowed to continue. The ionic detergent formed mixed micelles with the nonionic detergent. Thus charged, the mixed micelles migrated to either electrode, removing nonionic detergent from the fractionated proteins. Applying this technique to an adipose tissue preparation, detergent-inhibited activity of a lipolytic enzyme was restored and the binding of adenosine 3':5'-cyclic monophosphate (cyclic AMP) to a protein kinase was increased.", "contents": "Removal of nonionic detergent from proteins fractionated by electrofocusing. The nonionic detergent Nonipol TD 12 (an alkyl polyoxyethylene alcohol) has been removed from solubilised proteins after their fractionation by electrofocusing. Following electrofocusing in nonionic detergent an anionic or cationic detergent was added to the focussing medium and the focusing was allowed to continue. The ionic detergent formed mixed micelles with the nonionic detergent. Thus charged, the mixed micelles migrated to either electrode, removing nonionic detergent from the fractionated proteins. Applying this technique to an adipose tissue preparation, detergent-inhibited activity of a lipolytic enzyme was restored and the binding of adenosine 3':5'-cyclic monophosphate (cyclic AMP) to a protein kinase was increased."}
{"id": "PMID:205270", "title": "Multiple forms of cytosol and membrane-bound protein kinase activity in human erythrocytes.", "content": "Both cytosol and membranes of human erythrocytes display protein kinase activity towards exogenous protein substrates such as casein, phosvitin and histones. The histone kinase activity, unlike casein kinase, of both cytosol and membranes is increased by cyclic AMP. The protein kinase forms removed from the membranes with 0.7 M NaCl, phosphorylate only serine residues of both casein and histones through a mechanism cyclic AMP-independent. The protein kinase activity located in the cytosol (hemolysate) is due also to enzyme forms phosphorylating both serine and threonine residues of casein, in addition to forms phosphorylating only serine residues of casein and histones. Also the cytosol kinase forms, once partially purified by Sepharose 6B filtration, appear to be cyclic AMP-independent.", "contents": "Multiple forms of cytosol and membrane-bound protein kinase activity in human erythrocytes. Both cytosol and membranes of human erythrocytes display protein kinase activity towards exogenous protein substrates such as casein, phosvitin and histones. The histone kinase activity, unlike casein kinase, of both cytosol and membranes is increased by cyclic AMP. The protein kinase forms removed from the membranes with 0.7 M NaCl, phosphorylate only serine residues of both casein and histones through a mechanism cyclic AMP-independent. The protein kinase activity located in the cytosol (hemolysate) is due also to enzyme forms phosphorylating both serine and threonine residues of casein, in addition to forms phosphorylating only serine residues of casein and histones. Also the cytosol kinase forms, once partially purified by Sepharose 6B filtration, appear to be cyclic AMP-independent."}
{"id": "PMID:205271", "title": "Induction of cyclic AMP-binding proteins by dibutyryl cyclic AMP in mouse neuroblastoma cells.", "content": "Mouse neuroblastoma cells grown in the presence of 1 mM N6,O2'-dibutyryl-cyclic AMP showed a 3-fold increase in cyclic AMP-binding proteins. The role of dibutyryl cyclic AMP in the introduction of cyclic AMP-binding proteins in these cells has been studied. Induced cyclic AMP-binding proteins were observed in the cytoplasm 15 h after dibutyryl cyclic AMP treatment. The increase in cyclic AMP-binding proteins required RNA and protein synthesis. It is suggested that the 15-h lag occurs at the post-transcriptional and/or translational level. Cyclic AMP-binding proteins are found in both soluble and particulate cell fractions. Dibutyryl cyclic AMP increased binding proteins in both fractions. The control and dibutyryl cyclic AMP-induced binding proteins showed similar affinity for cyclic AMP. The data indicate that dibutyryl cyclic AMP caused the following sequential events: a 12-fold increase in cyclic AMP levels; a 40% increase in phosphodiesterase activity; and a 300% (3-fold) increase in cyclic AMP-binding proteins. It is suggested that the differentiation of mouse neuroblastoma cells involves increased levels of cyclic AMP and cyclic AMP-binding proteins.", "contents": "Induction of cyclic AMP-binding proteins by dibutyryl cyclic AMP in mouse neuroblastoma cells. Mouse neuroblastoma cells grown in the presence of 1 mM N6,O2'-dibutyryl-cyclic AMP showed a 3-fold increase in cyclic AMP-binding proteins. The role of dibutyryl cyclic AMP in the introduction of cyclic AMP-binding proteins in these cells has been studied. Induced cyclic AMP-binding proteins were observed in the cytoplasm 15 h after dibutyryl cyclic AMP treatment. The increase in cyclic AMP-binding proteins required RNA and protein synthesis. It is suggested that the 15-h lag occurs at the post-transcriptional and/or translational level. Cyclic AMP-binding proteins are found in both soluble and particulate cell fractions. Dibutyryl cyclic AMP increased binding proteins in both fractions. The control and dibutyryl cyclic AMP-induced binding proteins showed similar affinity for cyclic AMP. The data indicate that dibutyryl cyclic AMP caused the following sequential events: a 12-fold increase in cyclic AMP levels; a 40% increase in phosphodiesterase activity; and a 300% (3-fold) increase in cyclic AMP-binding proteins. It is suggested that the differentiation of mouse neuroblastoma cells involves increased levels of cyclic AMP and cyclic AMP-binding proteins."}
{"id": "PMID:205272", "title": "Synthesis and properties of a photoaffinity probe for the glucagon receptor in hepatocyte plasma membranes.", "content": "The reaction of glucagon with 4-fluoro-3-nitrophenylazide has been shown to afford the photosensitive derivative, Nepsilon-4-azido-2-nitrophenyl-glucagon. The structure and properties of this derivative were established by amino acid analysis, absorption and fluorescence spectroscopy, deamination, Edman degradation and photolysis. This photoaffinity derivative of glucagon has been used to label specifically glucagon binding sites on hepatocyte plasma membranes.", "contents": "Synthesis and properties of a photoaffinity probe for the glucagon receptor in hepatocyte plasma membranes. The reaction of glucagon with 4-fluoro-3-nitrophenylazide has been shown to afford the photosensitive derivative, Nepsilon-4-azido-2-nitrophenyl-glucagon. The structure and properties of this derivative were established by amino acid analysis, absorption and fluorescence spectroscopy, deamination, Edman degradation and photolysis. This photoaffinity derivative of glucagon has been used to label specifically glucagon binding sites on hepatocyte plasma membranes."}
{"id": "PMID:205273", "title": "beta-Adrenergic receptors in rat skeletal muscle. Effects of thyroidectomy.", "content": "Thyroid hormones may participate in the regulation of beta-adrenergic receptors in skeletal muscle sarcolemmal membrane. Since skeletal muscles are not innervated by sympathetic nerve endings, the biochemical mechanism involved in the control of beta-adrenergic receptors by thyroid hormones appears to be mediated by thyroid-induced regulation of serum levels of catecholamines.", "contents": "beta-Adrenergic receptors in rat skeletal muscle. Effects of thyroidectomy. Thyroid hormones may participate in the regulation of beta-adrenergic receptors in skeletal muscle sarcolemmal membrane. Since skeletal muscles are not innervated by sympathetic nerve endings, the biochemical mechanism involved in the control of beta-adrenergic receptors by thyroid hormones appears to be mediated by thyroid-induced regulation of serum levels of catecholamines."}
{"id": "PMID:205274", "title": "Inhibitory effects of glucocorticoids on collagen synthesis by mouse sponge granulomas and granuloma fibroblasts in culture.", "content": "The basis for the glucocorticoid-mediated decrease in tissue collagen was studied in mouse granulomas and in primary granuloma fibroblast cultures. Injection of mice for 12 days with dexamethasone (0.35 mg/kg body weight) resulted in a 50--70% inhibition of collagen synthesis and accumulation in polyvinyl sponge-induced granulomas whereas total protein synthesis was inhibited by only about 25%. The decreased collagen content of the granuloma was accounted for by both a reduced fibroblast number and diminished synthesis per cell. Growth rates, total protein synthesis and collagen synthesis were the same in granuloma fibroblast cultures derived from control or steroid-treated mice. However, addition of 3.10(-7) M hydrocortisone to the culture medium caused a 30--50% inhibition of both collagen and non-collagen protein synthesis in firbroblasts from either source. These inhibitory effects were dose- and time-dependent with a lag time of 12--24 h. Prolyl hydroxylase activity was reduced both in sponge granulomas from glucocorticoid-treated mice and in hydrocortisone-treated fibroblast cultures. However, protein synthesis was inhibited to the same extent as the inhibition of prolyl hydroxylase activity and there was no effect on peptidyl prolyl hydroxylation. These results indicate that the glucocorticoid-induced reduction of collagen synthesis and accumulation observed in mouse granulomas and primary granuloma fibroblast cultures is not specific for this protein. Furthermore, glucocorticoid-induced inhibition of collagen synthesis cannot be attributed to underhydroxylation of collagen prolyl residues.", "contents": "Inhibitory effects of glucocorticoids on collagen synthesis by mouse sponge granulomas and granuloma fibroblasts in culture. The basis for the glucocorticoid-mediated decrease in tissue collagen was studied in mouse granulomas and in primary granuloma fibroblast cultures. Injection of mice for 12 days with dexamethasone (0.35 mg/kg body weight) resulted in a 50--70% inhibition of collagen synthesis and accumulation in polyvinyl sponge-induced granulomas whereas total protein synthesis was inhibited by only about 25%. The decreased collagen content of the granuloma was accounted for by both a reduced fibroblast number and diminished synthesis per cell. Growth rates, total protein synthesis and collagen synthesis were the same in granuloma fibroblast cultures derived from control or steroid-treated mice. However, addition of 3.10(-7) M hydrocortisone to the culture medium caused a 30--50% inhibition of both collagen and non-collagen protein synthesis in firbroblasts from either source. These inhibitory effects were dose- and time-dependent with a lag time of 12--24 h. Prolyl hydroxylase activity was reduced both in sponge granulomas from glucocorticoid-treated mice and in hydrocortisone-treated fibroblast cultures. However, protein synthesis was inhibited to the same extent as the inhibition of prolyl hydroxylase activity and there was no effect on peptidyl prolyl hydroxylation. These results indicate that the glucocorticoid-induced reduction of collagen synthesis and accumulation observed in mouse granulomas and primary granuloma fibroblast cultures is not specific for this protein. Furthermore, glucocorticoid-induced inhibition of collagen synthesis cannot be attributed to underhydroxylation of collagen prolyl residues."}
{"id": "PMID:205275", "title": "Endogenous substrates of protein kinase in rat liver cell sap under different dietary conditions.", "content": "Liver cell sap from normally fed rats, rats fed with a high-carbohydrate diet and fasted rats was chromatographed on DEAE-cellulose (pH 7.0). The chromatogram from each diet group was analyzed for pyruvate kinase activity and endogenous substrates of cyclic AMP-stimulated protein kinase. The materials were pooled into five phosphorylatable fractions, in each of which phosphate incorporation at 0.1 mM and 1.0 mM [32P]ATP in the presence of cyclic AMP and protein kinase was determined. For characterization of the phosphorylatable components, thin-layer gel chromatography on Sephadex G-200 and polyacrylamide gel electrophoresis in detergent were used for determination of native and minimal molecular weights, respectively. Except for pyruvate kinase, eight components which incorporated at least 0.05 nmol of [32P]phosphate/g of liver were detected. The phosphorylation of four of them was stimulated by cyclic AMP. Their minimal molecular weights were 42000, 21000, 52000 and 49000. The component with a minimal molecular weight of 42000 seemed to have a native molecular weight of 160000. Both the 21000 and the 52000 component had a native molecular weight of about 110000-120000. The protein with a minimal molecular weight of 49000 could not be correlated with certainty to a native molecular weight. The proteins whose phosphorylation was not stimulated by cyclic AMP had minimal molecular weights of 54000, 39000, 34000 and 22000.", "contents": "Endogenous substrates of protein kinase in rat liver cell sap under different dietary conditions. Liver cell sap from normally fed rats, rats fed with a high-carbohydrate diet and fasted rats was chromatographed on DEAE-cellulose (pH 7.0). The chromatogram from each diet group was analyzed for pyruvate kinase activity and endogenous substrates of cyclic AMP-stimulated protein kinase. The materials were pooled into five phosphorylatable fractions, in each of which phosphate incorporation at 0.1 mM and 1.0 mM [32P]ATP in the presence of cyclic AMP and protein kinase was determined. For characterization of the phosphorylatable components, thin-layer gel chromatography on Sephadex G-200 and polyacrylamide gel electrophoresis in detergent were used for determination of native and minimal molecular weights, respectively. Except for pyruvate kinase, eight components which incorporated at least 0.05 nmol of [32P]phosphate/g of liver were detected. The phosphorylation of four of them was stimulated by cyclic AMP. Their minimal molecular weights were 42000, 21000, 52000 and 49000. The component with a minimal molecular weight of 42000 seemed to have a native molecular weight of 160000. Both the 21000 and the 52000 component had a native molecular weight of about 110000-120000. The protein with a minimal molecular weight of 49000 could not be correlated with certainty to a native molecular weight. The proteins whose phosphorylation was not stimulated by cyclic AMP had minimal molecular weights of 54000, 39000, 34000 and 22000."}
{"id": "PMID:205276", "title": "Cyclic AMP-mediated activation of hepatic glycogenolysis by fructose.", "content": "Isolated livers from fed and fasted rats were perfused for 30 min with recirculating blood-buffer medium containing no added substrate and then switched to a flow-through perfusion using the same medium for an additional 5, 10 and 30 min. Continuous infusion of fructose for the final 5, 10 or 30 min resulted in activation of glycogen phosphorylase, an increase in the activity of protein kinase, elevated levels of tissue adenosine 3', 5'-monophosphate (cyclic AMP), and no consistent effect on glycogen synthase. Infusion of glucose under the same conditions resulted in activation of glycogen synthase, inactivation of glycogen phosphorylase, no change in protein kinase, and no consistent change in tissue cyclic AMP. These results demonstrate that while glucose promotes hepatic glycogen synthesis, fructose promotes activation of the enzymatic cascade responsible for glycogen breakdown.", "contents": "Cyclic AMP-mediated activation of hepatic glycogenolysis by fructose. Isolated livers from fed and fasted rats were perfused for 30 min with recirculating blood-buffer medium containing no added substrate and then switched to a flow-through perfusion using the same medium for an additional 5, 10 and 30 min. Continuous infusion of fructose for the final 5, 10 or 30 min resulted in activation of glycogen phosphorylase, an increase in the activity of protein kinase, elevated levels of tissue adenosine 3', 5'-monophosphate (cyclic AMP), and no consistent effect on glycogen synthase. Infusion of glucose under the same conditions resulted in activation of glycogen synthase, inactivation of glycogen phosphorylase, no change in protein kinase, and no consistent change in tissue cyclic AMP. These results demonstrate that while glucose promotes hepatic glycogen synthesis, fructose promotes activation of the enzymatic cascade responsible for glycogen breakdown."}
{"id": "PMID:205277", "title": "Kinetics of cyclic AMP in toad bladder.", "content": "Tissue distributions of cyclic [3H]AMP and [14C]inulin in toad bladder were determined and their kinetics analyzed. We found that both the epithelial and the other cells of the toad bladder handle cyclic AMP similarly. Moreover, we found that the distribution of cyclic AMP did not differ from that of inulin, an extracellular marker. Kinetic analysis suggests that the rate coefficient of cyclic AMP metabolism is much larger than the exchange rate coefficient, which explains why distribution of both cyclic AMP and inulin are similar.", "contents": "Kinetics of cyclic AMP in toad bladder. Tissue distributions of cyclic [3H]AMP and [14C]inulin in toad bladder were determined and their kinetics analyzed. We found that both the epithelial and the other cells of the toad bladder handle cyclic AMP similarly. Moreover, we found that the distribution of cyclic AMP did not differ from that of inulin, an extracellular marker. Kinetic analysis suggests that the rate coefficient of cyclic AMP metabolism is much larger than the exchange rate coefficient, which explains why distribution of both cyclic AMP and inulin are similar."}
{"id": "PMID:205278", "title": "Electron spin resonance studies of the solution structure of vanadyl amino acid complexes and mixed ligand complexes of oxalate.", "content": "Esr and electronic spectra of complexes of the general composition VO(AA)2 and VO(ox)(AA) have been characterized; AA = gly, his, cys, pro, val, met, asp amino acids. Spectra of the formulation VO(ox)(LL) (with LL = imidazole plus monodentate oxalate, histamine plus monodentate oxalate, histidine, cysteine, 4-imidazolepropionic acid, mercaptopropionic acid, ethylenediamine and ethanolamine) have been used to deduce a self-consistent assignment of AL, a ligand donor additivity constant contribution to the observed hyperfine splitting, Aiso. Values of AL are sensitive to inductive effects in the ligand structure. The solution structures and likely coordination geometries of VO(his)2, and VO(cys)22-- are discussed. The role of the imidazole moiety as a sigma donor and sulfhydryl sulfur as a pi acceptor is observed in VO(AA)2 and VO(ox)(AA) complexes.", "contents": "Electron spin resonance studies of the solution structure of vanadyl amino acid complexes and mixed ligand complexes of oxalate. Esr and electronic spectra of complexes of the general composition VO(AA)2 and VO(ox)(AA) have been characterized; AA = gly, his, cys, pro, val, met, asp amino acids. Spectra of the formulation VO(ox)(LL) (with LL = imidazole plus monodentate oxalate, histamine plus monodentate oxalate, histidine, cysteine, 4-imidazolepropionic acid, mercaptopropionic acid, ethylenediamine and ethanolamine) have been used to deduce a self-consistent assignment of AL, a ligand donor additivity constant contribution to the observed hyperfine splitting, Aiso. Values of AL are sensitive to inductive effects in the ligand structure. The solution structures and likely coordination geometries of VO(his)2, and VO(cys)22-- are discussed. The role of the imidazole moiety as a sigma donor and sulfhydryl sulfur as a pi acceptor is observed in VO(AA)2 and VO(ox)(AA) complexes."}
{"id": "PMID:205279", "title": "Ontogeny of adenylate cyclase and phosphodiesterase activities in swine tissues.", "content": "The ontogenic patterns of the basal- and fluoride-stimulated adenylate cyclase and the cAMP phosphodiesterase activites as well as the tissue levels of cAMP were assessed in swine adipose tissue, heart, skeletal muscle, and liver. The developmental patterns were complex. However, there was a general tendency in all tissues toward lower enzyme activities in the oldest animals (150 days) for both enzymes. In adipose tissue, the decreased enzyme levels could partially be attributed to an increase in adipocyte size.", "contents": "Ontogeny of adenylate cyclase and phosphodiesterase activities in swine tissues. The ontogenic patterns of the basal- and fluoride-stimulated adenylate cyclase and the cAMP phosphodiesterase activites as well as the tissue levels of cAMP were assessed in swine adipose tissue, heart, skeletal muscle, and liver. The developmental patterns were complex. However, there was a general tendency in all tissues toward lower enzyme activities in the oldest animals (150 days) for both enzymes. In adipose tissue, the decreased enzyme levels could partially be attributed to an increase in adipocyte size."}
{"id": "PMID:205280", "title": "P-chloromercuribenzene sulfonate blocks and reverses the effect of amiloride on sodium transport across rabbit colon in vitro.", "content": "The addition of 10(-3) M p-chloromercuribenzene sulfonate (PCMBS) to the solution bathing the mucosal surface of rabbit colon has no effect on the rate of active Na transport but blocks or reverses the inhibitory action of amiloride. The tissue must be exposed to PCMBS for 20-30 min for a complete blocking effect, and removal of PCMBS from the mucosal solution after this period of exposure does not restore the sensitivity of the tissue to amiloride. The slow time-courses of the blocking and reversal effects suggest that PCMBS does not irreversibly interact with groups directly involved in the binding of amiloride.", "contents": "P-chloromercuribenzene sulfonate blocks and reverses the effect of amiloride on sodium transport across rabbit colon in vitro. The addition of 10(-3) M p-chloromercuribenzene sulfonate (PCMBS) to the solution bathing the mucosal surface of rabbit colon has no effect on the rate of active Na transport but blocks or reverses the inhibitory action of amiloride. The tissue must be exposed to PCMBS for 20-30 min for a complete blocking effect, and removal of PCMBS from the mucosal solution after this period of exposure does not restore the sensitivity of the tissue to amiloride. The slow time-courses of the blocking and reversal effects suggest that PCMBS does not irreversibly interact with groups directly involved in the binding of amiloride."}
{"id": "PMID:205282", "title": "Surface proteolytic activity in cell interactions: activation of human peripheral lymphocytes in contact with mitogen-treated glass-adherent leukocytes.", "content": "The transformation of lymphocytes by mitogens or by periodate treatment requires the presence of glass-adherent leukocytes. We have demonstrated that contact with periodate-treated adherent cells transforms human peripheral T lymphocytes. Using a new method to estimate proteolytic activity released by cells or available at cell surfaces, we found marked stimulation of cell surface-associated enzyme activity on glass-adherent cells treated by NaIO4 or by Con A. The expression of this enzymatic stimulation required contact with substrate, just as the transformation of untreated T cells required contact with treated adherent cells. Therefore, we propose that cell-cell interaction leads to an efficient mode of stimulation, which may be mediated by or initiated by surface-associated proteases of adherent cells.", "contents": "Surface proteolytic activity in cell interactions: activation of human peripheral lymphocytes in contact with mitogen-treated glass-adherent leukocytes. The transformation of lymphocytes by mitogens or by periodate treatment requires the presence of glass-adherent leukocytes. We have demonstrated that contact with periodate-treated adherent cells transforms human peripheral T lymphocytes. Using a new method to estimate proteolytic activity released by cells or available at cell surfaces, we found marked stimulation of cell surface-associated enzyme activity on glass-adherent cells treated by NaIO4 or by Con A. The expression of this enzymatic stimulation required contact with substrate, just as the transformation of untreated T cells required contact with treated adherent cells. Therefore, we propose that cell-cell interaction leads to an efficient mode of stimulation, which may be mediated by or initiated by surface-associated proteases of adherent cells."}
{"id": "PMID:205285", "title": "Specific alpha-adrenergic receptor desensitization in vascular smooth muscle.", "content": "Specific desensitization of vascular tissue to norepinephrine was studied using an open-ring-type strip preparation of rabbit aorta. Aortae were taken from untreated, reserpine-pretreated (0.1 mg/kg/day; 3, 5, or 7 days) and 6-hydroxydropamine-pretreated (50 mg/kg; 3 or 7 days before sacrifice) rabbits. Aortic strips from the pretreated rabbits were supersensitive to norepinephrine. Subsequent to obtaining the first dose-response curve for norepinephrine, aortic strips were less sensitive to norepinephrine. It was found that desensitization to norepinephrine occurred following 10 min preincubation with 10(-6)m norepinephrine, and 20 min preincubation with 10(-7)m norepinephrine. The desensitization of supersensitive strips was significantly greater than in controls. Dopamine and isoproterenol desensitized both untreated and pretreated strips to norepinephrine. Phenylephrine desensitized strips to norepinephrine from 6-hydroxydopamine-pretreated rabbits. Acetylcholine and potassium did not desensitize strips to norepinephrine; however, acetylcholine desensitized strips to acetylcholine. It is concluded from these studies that norepinephrine desensitization in a specific alpha-adrenergic-related event.", "contents": "Specific alpha-adrenergic receptor desensitization in vascular smooth muscle. Specific desensitization of vascular tissue to norepinephrine was studied using an open-ring-type strip preparation of rabbit aorta. Aortae were taken from untreated, reserpine-pretreated (0.1 mg/kg/day; 3, 5, or 7 days) and 6-hydroxydropamine-pretreated (50 mg/kg; 3 or 7 days before sacrifice) rabbits. Aortic strips from the pretreated rabbits were supersensitive to norepinephrine. Subsequent to obtaining the first dose-response curve for norepinephrine, aortic strips were less sensitive to norepinephrine. It was found that desensitization to norepinephrine occurred following 10 min preincubation with 10(-6)m norepinephrine, and 20 min preincubation with 10(-7)m norepinephrine. The desensitization of supersensitive strips was significantly greater than in controls. Dopamine and isoproterenol desensitized both untreated and pretreated strips to norepinephrine. Phenylephrine desensitized strips to norepinephrine from 6-hydroxydopamine-pretreated rabbits. Acetylcholine and potassium did not desensitize strips to norepinephrine; however, acetylcholine desensitized strips to acetylcholine. It is concluded from these studies that norepinephrine desensitization in a specific alpha-adrenergic-related event."}
{"id": "PMID:205288", "title": "Beta-adrenoceptor mediated inhibition by terbutaline of histamine effects on vascular permeability.", "content": "1 In guinea-pigs, previously given Evans blue dye intravenously, 13 to 18 intradermal injections of histamine, with or without other drugs, were made into the depilated trunk skin. Dye was then quantitatively extracted from each skin area and the measured absorbance values were used as a measure of vascular leakage of macromolecules. 2 Histamine (0.5 to 12 nmol) produced dose-related increased in vascular leakage. These were reduced by terbutaline (1 and 10 nmol) which produced a significant shift in the histamine dose-response lines to lower absorbance values. The effect of 0.1 nmol of terbutaline was significant only against doses of histamine of less than 2 nmol. 3 Propranolol (1 nmol and 10 nmol) antagonized the effects of terbutaline. Propranolol, at a dose of 10 nmol but not 1 nmol, itself reduced the responses to 1.5 nmol histamine. 4 We conclude that the inhibition by terbutaline of histamine-induced dye leakage in guinea-pig skin is mediated by stimulation of beta-adrenoceptors and its is suggested that this effect of terbutaline occurs directly on beta-receptors at the vascular leakage site.", "contents": "Beta-adrenoceptor mediated inhibition by terbutaline of histamine effects on vascular permeability. 1 In guinea-pigs, previously given Evans blue dye intravenously, 13 to 18 intradermal injections of histamine, with or without other drugs, were made into the depilated trunk skin. Dye was then quantitatively extracted from each skin area and the measured absorbance values were used as a measure of vascular leakage of macromolecules. 2 Histamine (0.5 to 12 nmol) produced dose-related increased in vascular leakage. These were reduced by terbutaline (1 and 10 nmol) which produced a significant shift in the histamine dose-response lines to lower absorbance values. The effect of 0.1 nmol of terbutaline was significant only against doses of histamine of less than 2 nmol. 3 Propranolol (1 nmol and 10 nmol) antagonized the effects of terbutaline. Propranolol, at a dose of 10 nmol but not 1 nmol, itself reduced the responses to 1.5 nmol histamine. 4 We conclude that the inhibition by terbutaline of histamine-induced dye leakage in guinea-pig skin is mediated by stimulation of beta-adrenoceptors and its is suggested that this effect of terbutaline occurs directly on beta-receptors at the vascular leakage site."}
{"id": "PMID:205289", "title": "The effects of a toxin isolated from Australian tiger snake (Notechis scutatus scutatus) venom on autonomic neuromuscular transmission.", "content": "1 The effects on mammalian autonomic neuromuscular transmission of a purified toxin from the crude venom of the Australian tiger snake, Notechis scutatus, have been investigated. 2 The toxin had no measurable effect on transmission in either the rat anococcygeus, the rat vas deferens, or the longitudinal muscle of the guinea-pig ileum. 3 The toxin induced a contraction of longitudinal smooth muscle of the ileum. The tissue relaxed in spite of the continued presence of the toxin, and remained insensitive to further doses. The contractile response was not mediated by either cholinergic or histaminergic mechanisms. 4 The toxin caused an inhibition of the response to field stimulation of the guinea-pig vas deferens and the guinea-pig seminal vesicle. The inhibition was spontaneously reversible, and the preparations remained insensitive to further doses fo the toxin. The effects of the toxin were not mediated by either prostaglandins or by noradrenaline. 5 The inhibitory effects of a variety of compounds known to act at presynaptic sites were also blocked by exposure to the toxin; inhibition caused by postsynaptic activity was unaffected by the toxin. 6 It is suggested that the toxin inhibits transmission in the guinea-pig vas deferens and seminal vesicle by a presynaptic mechanism. 7 The possibility that the mechanism involves phospholipase A2 activity is discussed.", "contents": "The effects of a toxin isolated from Australian tiger snake (Notechis scutatus scutatus) venom on autonomic neuromuscular transmission. 1 The effects on mammalian autonomic neuromuscular transmission of a purified toxin from the crude venom of the Australian tiger snake, Notechis scutatus, have been investigated. 2 The toxin had no measurable effect on transmission in either the rat anococcygeus, the rat vas deferens, or the longitudinal muscle of the guinea-pig ileum. 3 The toxin induced a contraction of longitudinal smooth muscle of the ileum. The tissue relaxed in spite of the continued presence of the toxin, and remained insensitive to further doses. The contractile response was not mediated by either cholinergic or histaminergic mechanisms. 4 The toxin caused an inhibition of the response to field stimulation of the guinea-pig vas deferens and the guinea-pig seminal vesicle. The inhibition was spontaneously reversible, and the preparations remained insensitive to further doses fo the toxin. The effects of the toxin were not mediated by either prostaglandins or by noradrenaline. 5 The inhibitory effects of a variety of compounds known to act at presynaptic sites were also blocked by exposure to the toxin; inhibition caused by postsynaptic activity was unaffected by the toxin. 6 It is suggested that the toxin inhibits transmission in the guinea-pig vas deferens and seminal vesicle by a presynaptic mechanism. 7 The possibility that the mechanism involves phospholipase A2 activity is discussed."}
{"id": "PMID:205290", "title": "Vasoactive intestinal polypeptide promotes cyclic adenosine 3',5'-monophosphate accumulation in guinea-pig trachea.", "content": "Cyclic adenosine 3',5'-monophosphage (cyclic AMP) levels in guinea-pig tracheal rings increased on incubation with the vasoactive intestinal peptide (VIP). The effect was potentiated by the addition of theophylline. The results suggest that the tracheo-bronchial relaxant action of VIP may be mediated by stimulation of tracheal adenylyl cyclase.", "contents": "Vasoactive intestinal polypeptide promotes cyclic adenosine 3',5'-monophosphate accumulation in guinea-pig trachea. Cyclic adenosine 3',5'-monophosphage (cyclic AMP) levels in guinea-pig tracheal rings increased on incubation with the vasoactive intestinal peptide (VIP). The effect was potentiated by the addition of theophylline. The results suggest that the tracheo-bronchial relaxant action of VIP may be mediated by stimulation of tracheal adenylyl cyclase."}
{"id": "PMID:205302", "title": "An alternative to group homes.", "content": "This paper describes a supported lodgings scheme as an alternative to group homes. It is pointed out that the County Council has a statutory duty to finance supported lodgings and that schizophrenics are ideally suited to such a scheme. Some short-stay, the majority of the 'new' non-demented long-stay, and a large number of the 'old' long-stay patients have been discharged by this means. After-care facilities were important, as nearly half attended the day centre and over one third were regularly visited in their lodgings by the community psychiatric nurses and social workers.", "contents": "An alternative to group homes. This paper describes a supported lodgings scheme as an alternative to group homes. It is pointed out that the County Council has a statutory duty to finance supported lodgings and that schizophrenics are ideally suited to such a scheme. Some short-stay, the majority of the 'new' non-demented long-stay, and a large number of the 'old' long-stay patients have been discharged by this means. After-care facilities were important, as nearly half attended the day centre and over one third were regularly visited in their lodgings by the community psychiatric nurses and social workers."}
{"id": "PMID:205303", "title": "Cyclic AMP, adrenaline and noradrenaline in plasma during surgery.", "content": "Plasma concentrations of cyclic AMP, adrenaline and noradrenaline were measured in 6 patients undergoing hysterectomy from before induction of anaesthesia to 6 h after skin incision. Noradrenaline did not vary significantly during the observation period, whereas cyclic AMP and adrenaline increased after skin incision. A significant correlation was found between plasma concentrations of cyclic AMP and adrenaline (r = 0.84, P less than 0.01), suggesting that the latter is responsible for the increase in plasma cyclic AMP which is observed in relation to surgical procedures. Peak concentrations of cyclic AMP and adrenaline were seen in the early postoperative phase. This indicates that the most pronounced acute endocrine stress response to surgery of moderate severity occurs after termination of anaesthesia.", "contents": "Cyclic AMP, adrenaline and noradrenaline in plasma during surgery. Plasma concentrations of cyclic AMP, adrenaline and noradrenaline were measured in 6 patients undergoing hysterectomy from before induction of anaesthesia to 6 h after skin incision. Noradrenaline did not vary significantly during the observation period, whereas cyclic AMP and adrenaline increased after skin incision. A significant correlation was found between plasma concentrations of cyclic AMP and adrenaline (r = 0.84, P less than 0.01), suggesting that the latter is responsible for the increase in plasma cyclic AMP which is observed in relation to surgical procedures. Peak concentrations of cyclic AMP and adrenaline were seen in the early postoperative phase. This indicates that the most pronounced acute endocrine stress response to surgery of moderate severity occurs after termination of anaesthesia."}
{"id": "PMID:205304", "title": "Clinically silent gross hypergastrinaemia from a multiple hormone-secreting pancreatic apudoma.", "content": "A patient is described who had a malignant pancreatic islet cell apudoma secreting corticotrophin (ACTH) and melanocyte-stimulating hormone (MSH), both of which were clinically active, and very large quantities of immunoreactive gastrins, which were biologically active but clinically silent (normal gastric acid secretion and no peptic ulceration). The presence of parietal cell antibodies, with no increase in the plasma concentrations of hormones which can inhibit gastric acid secretion (secretin, GIP and VIP), suggests that many of the of the parietal cells may have been blocked by the autoantibodies.", "contents": "Clinically silent gross hypergastrinaemia from a multiple hormone-secreting pancreatic apudoma. A patient is described who had a malignant pancreatic islet cell apudoma secreting corticotrophin (ACTH) and melanocyte-stimulating hormone (MSH), both of which were clinically active, and very large quantities of immunoreactive gastrins, which were biologically active but clinically silent (normal gastric acid secretion and no peptic ulceration). The presence of parietal cell antibodies, with no increase in the plasma concentrations of hormones which can inhibit gastric acid secretion (secretin, GIP and VIP), suggests that many of the of the parietal cells may have been blocked by the autoantibodies."}
{"id": "PMID:205305", "title": "Reactions after pertussis vaccine: a manufacturer's experiences and difficulties since 1964.", "content": "Pertussis vaccines vary in quality, safety, and efficacy according to the production strains of Bordetella pertussis, the method of manufacture, and quality control procedures. It is therefore not justifiable to combine information on the incidence, nature, and severity of reactions after all manufacturers' pertussis vaccines as if they were a single product. Attempts were made to collect information on all suspected cases of severe reactions that occurred after administration of about 15 million doses of Wellcome pertussis vaccines in the United Kingdom and Northern Ireland from 1964 to mid-1977. Altogether six deaths, six neurological reactions with sequelae, and 17 convulsions without sequelae were reported, but some were clearly not attributable to the vaccine, while, in other cases, the available information was inadequate for assessing the role of vaccination. Neurological disorders, similar to those reported in a few children after pertussis vaccination, occur unexpectedly in apparently healthy infants at the recommended age for immunisation, so chance association between vaccination and these events can be expected in some children. The Joint Committee on Vaccination and Immunisation has made several recommendations aimed at reducing severe reactions after pertussis vaccination. These include replacing plain vaccine with aluminium-adsorbed vaccine, but there is no clear evidence that the aluminium-adsorbed vaccine produces fewer reactions than the plain.There are difficulties enough in deciding the cause of events that occur after vaccination, since these reactions often occur naturally in children of vaccination age. The task is made even harder by the assumption that various manufacturers' vaccines are the same and the lack of information available to manufacturers about cases in which their vaccine has been implicated. Information on vaccines administered is entered on immunisation records cards; it should be used and referred to if reactions occur.", "contents": "Reactions after pertussis vaccine: a manufacturer's experiences and difficulties since 1964. Pertussis vaccines vary in quality, safety, and efficacy according to the production strains of Bordetella pertussis, the method of manufacture, and quality control procedures. It is therefore not justifiable to combine information on the incidence, nature, and severity of reactions after all manufacturers' pertussis vaccines as if they were a single product. Attempts were made to collect information on all suspected cases of severe reactions that occurred after administration of about 15 million doses of Wellcome pertussis vaccines in the United Kingdom and Northern Ireland from 1964 to mid-1977. Altogether six deaths, six neurological reactions with sequelae, and 17 convulsions without sequelae were reported, but some were clearly not attributable to the vaccine, while, in other cases, the available information was inadequate for assessing the role of vaccination. Neurological disorders, similar to those reported in a few children after pertussis vaccination, occur unexpectedly in apparently healthy infants at the recommended age for immunisation, so chance association between vaccination and these events can be expected in some children. The Joint Committee on Vaccination and Immunisation has made several recommendations aimed at reducing severe reactions after pertussis vaccination. These include replacing plain vaccine with aluminium-adsorbed vaccine, but there is no clear evidence that the aluminium-adsorbed vaccine produces fewer reactions than the plain.There are difficulties enough in deciding the cause of events that occur after vaccination, since these reactions often occur naturally in children of vaccination age. The task is made even harder by the assumption that various manufacturers' vaccines are the same and the lack of information available to manufacturers about cases in which their vaccine has been implicated. Information on vaccines administered is entered on immunisation records cards; it should be used and referred to if reactions occur."}
{"id": "PMID:205308", "title": "High-density and low-density lipoproteins and prevalence of vascular disease in diabetes mellitus.", "content": "The prevalence of vascular disease among 154 diabetic patients was analysed in relation to the serum concentrations of individual lipoproteins. Overal the presence of vascular disease (59 cases) was positively associated with serum cholesterol and low-density-lipoprotein cholesterol but negatively associated with high-density-lipoprotein (HDL) cholesterol. The negative relation between HDL and vascular disease was not observed in all subgroups of diabetics. We conclude that there may be no overriding association between HDL and vascular disease in diabetics as proposed for some non-diabetic populations.", "contents": "High-density and low-density lipoproteins and prevalence of vascular disease in diabetes mellitus. The prevalence of vascular disease among 154 diabetic patients was analysed in relation to the serum concentrations of individual lipoproteins. Overal the presence of vascular disease (59 cases) was positively associated with serum cholesterol and low-density-lipoprotein cholesterol but negatively associated with high-density-lipoprotein (HDL) cholesterol. The negative relation between HDL and vascular disease was not observed in all subgroups of diabetics. We conclude that there may be no overriding association between HDL and vascular disease in diabetics as proposed for some non-diabetic populations."}
{"id": "PMID:205318", "title": "Effects of some conformationally restricted GABA analogues on GABA membrane binding and nerve ending transport.", "content": "By using a series of aminocyclopentane- and aminocyclohexanecarboxylic acids, as well as some naturally occurring amino acids, it was possible to determine some aspects of the spatial topography of the GABA membrane binding and transport sites. The NA-independent GABA binding site was found to have a different spatial topography than the Na-dependent binding site in that trans-3-aminocyclopentanecarboxylic acid (trans-3-ACPC) was 7 times more potent than cis-3-ACPC to inhibit Na-independent binding, but only 1.6 times more potent to inhibit Na-dependent binding. The nerve ending GABA transport site was found to be similar to the Na-dependent GABA binding site in that it will accommodate both cis- and trans-3-ACPC. However, the transport site differs from the binding site in that cis-3-aminocyclohexanecarboxylic acid (cis-3-ACHC) is a potent inhibitor of transport but a weak inhibitor of binding. In addition to the differences in spatial characteristics, differences in the subcellular distribution of Na-independent and Na-dependent binding sites were observed. The former were found primarily in the nerve ending-mitochondrial fraction, while the latter were primarily found in the microsomal fraction.", "contents": "Effects of some conformationally restricted GABA analogues on GABA membrane binding and nerve ending transport. By using a series of aminocyclopentane- and aminocyclohexanecarboxylic acids, as well as some naturally occurring amino acids, it was possible to determine some aspects of the spatial topography of the GABA membrane binding and transport sites. The NA-independent GABA binding site was found to have a different spatial topography than the Na-dependent binding site in that trans-3-aminocyclopentanecarboxylic acid (trans-3-ACPC) was 7 times more potent than cis-3-ACPC to inhibit Na-independent binding, but only 1.6 times more potent to inhibit Na-dependent binding. The nerve ending GABA transport site was found to be similar to the Na-dependent GABA binding site in that it will accommodate both cis- and trans-3-ACPC. However, the transport site differs from the binding site in that cis-3-aminocyclohexanecarboxylic acid (cis-3-ACHC) is a potent inhibitor of transport but a weak inhibitor of binding. In addition to the differences in spatial characteristics, differences in the subcellular distribution of Na-independent and Na-dependent binding sites were observed. The former were found primarily in the nerve ending-mitochondrial fraction, while the latter were primarily found in the microsomal fraction."}
{"id": "PMID:205319", "title": "Receptors for gamma-aminobutyric acid (GABA) on Aplysia neurons.", "content": "Aplysia neurons show 5 different types of response (three excitatory and two inhibitory) to iontophoretic application of gamma-aminobutyric acid (GABA). Four of these are associated with a membrane conductance increase, but one is associated with a conductance decrease. The most common response is a fast hyperpolarization which reverses at about--58 mV and is sensitive to manipulation of external Cl- concentration, and thus is due to a specific increase in Cl- conductance. There is an infrequent, slower hyperpolarizing response which does not reverse above about--80 mV and is insensitive to external Cl-. This response appears to result from a conductance increase to K+. Two types of depolarizing responses are associated with conductance increases. These responses differ in their latency, duration and sensitivity to curare. The more frequent is relatively rapid (peak at 1-2 sec) and is depressed by curare at high concentrations. In other neurons, GABA causes a slower response, peaking at 6-10 sec, which is not curare-sensitive. Usually for both types of response, the voltage and conductance changes are completely abolished by perfusion with Na+-free seawater, and the responses cannot be reversed with depolarization. In other neurons such as L11, the response can be reversed with depolarization, and appears to result from a conductance increase to both Na+ and Cl-. In neuron R15, GABA causes a slow depolarizing response (peak at about 9 sec) which is associated with a decreased membrane conductance, probably to K+. The classical GABA antagonists, picrotoxin and bicuculline, block Cl- responses but no others, while the fast Na+ and Cl- responses are depressed by curare. Strychnine does not affect any GABA response. The multiplicity of GABA responses, the specificity of their organization and the fact that only some neurons have receptors for GABA, argue that GABA may have a role as a neurotransmitter in Aplysia. Furthermore, the existence of several types of excitatory GABA response suggests that GABA may function both as an inhibitory and excitatory neurotransmitter.", "contents": "Receptors for gamma-aminobutyric acid (GABA) on Aplysia neurons. Aplysia neurons show 5 different types of response (three excitatory and two inhibitory) to iontophoretic application of gamma-aminobutyric acid (GABA). Four of these are associated with a membrane conductance increase, but one is associated with a conductance decrease. The most common response is a fast hyperpolarization which reverses at about--58 mV and is sensitive to manipulation of external Cl- concentration, and thus is due to a specific increase in Cl- conductance. There is an infrequent, slower hyperpolarizing response which does not reverse above about--80 mV and is insensitive to external Cl-. This response appears to result from a conductance increase to K+. Two types of depolarizing responses are associated with conductance increases. These responses differ in their latency, duration and sensitivity to curare. The more frequent is relatively rapid (peak at 1-2 sec) and is depressed by curare at high concentrations. In other neurons, GABA causes a slower response, peaking at 6-10 sec, which is not curare-sensitive. Usually for both types of response, the voltage and conductance changes are completely abolished by perfusion with Na+-free seawater, and the responses cannot be reversed with depolarization. In other neurons such as L11, the response can be reversed with depolarization, and appears to result from a conductance increase to both Na+ and Cl-. In neuron R15, GABA causes a slow depolarizing response (peak at about 9 sec) which is associated with a decreased membrane conductance, probably to K+. The classical GABA antagonists, picrotoxin and bicuculline, block Cl- responses but no others, while the fast Na+ and Cl- responses are depressed by curare. Strychnine does not affect any GABA response. The multiplicity of GABA responses, the specificity of their organization and the fact that only some neurons have receptors for GABA, argue that GABA may have a role as a neurotransmitter in Aplysia. Furthermore, the existence of several types of excitatory GABA response suggests that GABA may function both as an inhibitory and excitatory neurotransmitter."}
{"id": "PMID:205320", "title": "Serotonin nerve terminals in the locus coeruleus of adult rat: a radioautographic study.", "content": "Serotonin (5-HT) nerve terminals in the locus coeruleus (LC) of adult rat were visualized by high-resolution radioautography, in order to examine their distribution, fine structural features and intimate relationships with norepinephrine neurons. In animals pretreated with a monoamine oxidase inhibitor, prolonged intraventricular perfusion of 10(-4) M [3H]5-HT resulted in a specific identification of most if not all 5-HT axonal varicosities in LC. These terminals were equally distributed between the dorsal and ventral divisions of the nucleus. Their density was approximated at 10(7) per cu.mm within the middle third of the LC. In electron microscope radioautographs, the labeled 5-HT varicosities averaged 0.9 micron in diameter. They all exhibited a distinctive storage organelle, in the form of microvesicles and microcanaliculi (15-25 nm in diameter) partly filled with electron-dense material and usually aggregated in association with several large dense-core vesicles. While this finding of intrinsic morphological characteristics appeared compatible with a special cellular origin or regional differentiation, it was also suggestive of particular functional properties and/or mode of action. In a sample comprised of some 500 sectional profiles from labeled 5-HT varicosities in LC, a small proportion only (less than 10%) exhibited morphologically defined synaptic junctions. These rare contacts were invariably made with dendritic processes and never observed on the noradrenergic perikarya. It is therefore concluded that, in the LC, non-synaptic as well as synaptic mechanisms might be involved in the modulation and transneuronal regulation of norepinephrine neurons by 5-HT afferents.", "contents": "Serotonin nerve terminals in the locus coeruleus of adult rat: a radioautographic study. Serotonin (5-HT) nerve terminals in the locus coeruleus (LC) of adult rat were visualized by high-resolution radioautography, in order to examine their distribution, fine structural features and intimate relationships with norepinephrine neurons. In animals pretreated with a monoamine oxidase inhibitor, prolonged intraventricular perfusion of 10(-4) M [3H]5-HT resulted in a specific identification of most if not all 5-HT axonal varicosities in LC. These terminals were equally distributed between the dorsal and ventral divisions of the nucleus. Their density was approximated at 10(7) per cu.mm within the middle third of the LC. In electron microscope radioautographs, the labeled 5-HT varicosities averaged 0.9 micron in diameter. They all exhibited a distinctive storage organelle, in the form of microvesicles and microcanaliculi (15-25 nm in diameter) partly filled with electron-dense material and usually aggregated in association with several large dense-core vesicles. While this finding of intrinsic morphological characteristics appeared compatible with a special cellular origin or regional differentiation, it was also suggestive of particular functional properties and/or mode of action. In a sample comprised of some 500 sectional profiles from labeled 5-HT varicosities in LC, a small proportion only (less than 10%) exhibited morphologically defined synaptic junctions. These rare contacts were invariably made with dendritic processes and never observed on the noradrenergic perikarya. It is therefore concluded that, in the LC, non-synaptic as well as synaptic mechanisms might be involved in the modulation and transneuronal regulation of norepinephrine neurons by 5-HT afferents."}
{"id": "PMID:205321", "title": "A comparison of the inhibitory effects of taurine and GABA on identified Purkinje cells and other neurons in the cerebellar cortex of the rat.", "content": "The microiontophoretic application of taurine and GABA was studied in the cerebellar cortex of the rat. Both taurine and GABA produced a dose-dependent depression of spike frequency of cerebellar neurons. GABA (2-42 nA, mean 27 nA) induced an inhibition of spike discharge on all 138 cells tested, including 29 Purkinje cells. Taurine (60-200 nA, mean 108 nA) induced an inhibition of spike discharge on 93 of the 106 cerebellar neurons tested, including inhibition on 22 of 25 Purkinje cells. Iontophoretic application of bicuculline and picrotoxin antagonized the inhibitory effects of both GABA and taurine on Purkinje cells as well as on cerebellar neurons in general. Strychnine did not antagonize the inhibition of either GABA or taurine. Simultaneous application of taurine and GABA produced a synergistic inhibitory effect on the firing rate of Purkinje cells. Taurine, in contrast to GABA, appeared to be more depressant when applied in the Purkinje cell dendritic zone than when applied near the soma. The data are discussed in terms of taurine functioning as a neurotransmitter in the cerebellum of the rat and having receptor sites distinct from those for GABA.", "contents": "A comparison of the inhibitory effects of taurine and GABA on identified Purkinje cells and other neurons in the cerebellar cortex of the rat. The microiontophoretic application of taurine and GABA was studied in the cerebellar cortex of the rat. Both taurine and GABA produced a dose-dependent depression of spike frequency of cerebellar neurons. GABA (2-42 nA, mean 27 nA) induced an inhibition of spike discharge on all 138 cells tested, including 29 Purkinje cells. Taurine (60-200 nA, mean 108 nA) induced an inhibition of spike discharge on 93 of the 106 cerebellar neurons tested, including inhibition on 22 of 25 Purkinje cells. Iontophoretic application of bicuculline and picrotoxin antagonized the inhibitory effects of both GABA and taurine on Purkinje cells as well as on cerebellar neurons in general. Strychnine did not antagonize the inhibition of either GABA or taurine. Simultaneous application of taurine and GABA produced a synergistic inhibitory effect on the firing rate of Purkinje cells. Taurine, in contrast to GABA, appeared to be more depressant when applied in the Purkinje cell dendritic zone than when applied near the soma. The data are discussed in terms of taurine functioning as a neurotransmitter in the cerebellum of the rat and having receptor sites distinct from those for GABA."}
{"id": "PMID:205322", "title": "Tissue culture analysis of neurogenesis: myelination and synapse formation are retarded by serum deprivation.", "content": "Explants from newborn mouse cerebellum were cultured in nutrient media containing either adequate (30%) or low (15% or 7.5%) serum content. By light microscopic observation, delayed and inhibited myelination was detected in cultures fed with low serum media (experimental cultures). Specific activities of two enzymes related to myelin synthesis, 2',3'-cyclic nucleotide-3'-phosphohydrolase and 3-hydroxy-3-methylglutaryl coenzyme A reductase, were also reduced in experimental cultures. Morphometric analysis of electron micrographs showed that the size of presynaptic endings and total area occupied by synapses in experimental cultures were substantially reduced, while synaptic density per unit area increased. Reflecting the results of synaptic underdevelopment, the levels of two neurotransmitter enzymes, choline acetyltransferase and glutamic acid decarboxylase, were also decreased in experimental cultures.", "contents": "Tissue culture analysis of neurogenesis: myelination and synapse formation are retarded by serum deprivation. Explants from newborn mouse cerebellum were cultured in nutrient media containing either adequate (30%) or low (15% or 7.5%) serum content. By light microscopic observation, delayed and inhibited myelination was detected in cultures fed with low serum media (experimental cultures). Specific activities of two enzymes related to myelin synthesis, 2',3'-cyclic nucleotide-3'-phosphohydrolase and 3-hydroxy-3-methylglutaryl coenzyme A reductase, were also reduced in experimental cultures. Morphometric analysis of electron micrographs showed that the size of presynaptic endings and total area occupied by synapses in experimental cultures were substantially reduced, while synaptic density per unit area increased. Reflecting the results of synaptic underdevelopment, the levels of two neurotransmitter enzymes, choline acetyltransferase and glutamic acid decarboxylase, were also decreased in experimental cultures."}
{"id": "PMID:205327", "title": "The levels of apolipoprotein-E in hypercholesterolemic rat serum.", "content": "The levels of apolipoprotein-C (apo-E) in serum and isolated liproproteins from diet-induced hypercholesterolemic, and to some extent hypertriglycerdemic rats were measured by electroimmunoassay. The hypocholesterolemia was accompanied by a mild hypertriglyceridemia. The apo-E was increased by 60% in the hypercholesterolemic serum with a 5- and 50-fold increase in very low density lipoproteins (VLDL) and low density lipoproteins (LDL) respectively. However, the proportion of apo-E in nascent VLDL isolated from the hepatic Golgi apparatus of hypercholesterolemic rats was significantly decreased. In control serum, 40--50% of the apo-E is found in the density greater than 1.21 g/ml fraction, although this is at least partially due to ultracentrifugation. The aproprotein is absent from the density greater than 1.21 g/ml fraction from hypercholesterolemic serum, suggesting that it is bound more firmly to the lipoprotein complex. It is concluded that the large increases in apo-E in the VLDL and LDL density ranges of serum from hypercholesterolemic rats may in part be accounted for by the utilization of apo-E normally found at higher densities.", "contents": "The levels of apolipoprotein-E in hypercholesterolemic rat serum. The levels of apolipoprotein-C (apo-E) in serum and isolated liproproteins from diet-induced hypercholesterolemic, and to some extent hypertriglycerdemic rats were measured by electroimmunoassay. The hypocholesterolemia was accompanied by a mild hypertriglyceridemia. The apo-E was increased by 60% in the hypercholesterolemic serum with a 5- and 50-fold increase in very low density lipoproteins (VLDL) and low density lipoproteins (LDL) respectively. However, the proportion of apo-E in nascent VLDL isolated from the hepatic Golgi apparatus of hypercholesterolemic rats was significantly decreased. In control serum, 40--50% of the apo-E is found in the density greater than 1.21 g/ml fraction, although this is at least partially due to ultracentrifugation. The aproprotein is absent from the density greater than 1.21 g/ml fraction from hypercholesterolemic serum, suggesting that it is bound more firmly to the lipoprotein complex. It is concluded that the large increases in apo-E in the VLDL and LDL density ranges of serum from hypercholesterolemic rats may in part be accounted for by the utilization of apo-E normally found at higher densities."}
{"id": "PMID:205329", "title": "Comparison of rotavirus strains by hemagglutination inhibition.", "content": "Rotaviruses have been shown to be of importance as aetiologic agents of gastroenteritis in infants and in domestic animals of several species. Hemagglutinins were prepared from two Canadian isolates of bovine rotavirus and from one isolate of a simian rotavirus. A United Kingdon isolate of bovine rotavirus was shown not to possess hemagglutinating activity, indicating a strain difference between a Canadian and United Kingdom bovine rotavirus. In hemagglutination-inhibition (HAI) tests a rabbit hyperimmune (two injections) serum, prepared to one of the bovine rotaviruses, was not helpful in distinguishing the two bovine viruses because of cross-reactions between the viruses. However, it was possible to distinguish the bovine viruses from the simian virus with this serum. When guinea pig immune sera were prepared to the four rotavirus strains and tested with the three hemagglutinins in the HAI test, antigenic differences between the four strains of rotavirus were demonstrated. Hyperimmune guinea pig serum prepared to a strain of human rotavirus did not inhibit any of three hemagglutinins indicating that the human strain is different from the three rotavirus strains which gave hemagglutinins.", "contents": "Comparison of rotavirus strains by hemagglutination inhibition. Rotaviruses have been shown to be of importance as aetiologic agents of gastroenteritis in infants and in domestic animals of several species. Hemagglutinins were prepared from two Canadian isolates of bovine rotavirus and from one isolate of a simian rotavirus. A United Kingdon isolate of bovine rotavirus was shown not to possess hemagglutinating activity, indicating a strain difference between a Canadian and United Kingdom bovine rotavirus. In hemagglutination-inhibition (HAI) tests a rabbit hyperimmune (two injections) serum, prepared to one of the bovine rotaviruses, was not helpful in distinguishing the two bovine viruses because of cross-reactions between the viruses. However, it was possible to distinguish the bovine viruses from the simian virus with this serum. When guinea pig immune sera were prepared to the four rotavirus strains and tested with the three hemagglutinins in the HAI test, antigenic differences between the four strains of rotavirus were demonstrated. Hyperimmune guinea pig serum prepared to a strain of human rotavirus did not inhibit any of three hemagglutinins indicating that the human strain is different from the three rotavirus strains which gave hemagglutinins."}
{"id": "PMID:205331", "title": "Inhibition of protein synthesis in Streptococcus faecalis by ochratoxin A.", "content": "A non-competitive inhibition of binding of cAMP to bovine protein kinase by ochratoxin A (OTA) is shown. Preliminary evidence of a protein kinase in Streptococcus faecalis is presented. The cAMP stimulation of this kinase is also inhibited by OTA. At the lowest OTA concentrations, RNA and protein synthesis are inhibited in S. faecalis. The inhibition of RNA synthesis is secondary, as in the presence of chloramphenicol no inhibition occurs for 10 min after the addition of OTA. The synthesis but not the induction of beta-P-galactosidase is inhibited by OTA. The polysomes of S. faecalis are stabilized after addition of OTA, showing an inhibition of peptide elongation. The model of action of OTA in bacteria is discussed and it is concluded that inhibition of protein synthesis is the process which might be closest to the primary target of OTA.", "contents": "Inhibition of protein synthesis in Streptococcus faecalis by ochratoxin A. A non-competitive inhibition of binding of cAMP to bovine protein kinase by ochratoxin A (OTA) is shown. Preliminary evidence of a protein kinase in Streptococcus faecalis is presented. The cAMP stimulation of this kinase is also inhibited by OTA. At the lowest OTA concentrations, RNA and protein synthesis are inhibited in S. faecalis. The inhibition of RNA synthesis is secondary, as in the presence of chloramphenicol no inhibition occurs for 10 min after the addition of OTA. The synthesis but not the induction of beta-P-galactosidase is inhibited by OTA. The polysomes of S. faecalis are stabilized after addition of OTA, showing an inhibition of peptide elongation. The model of action of OTA in bacteria is discussed and it is concluded that inhibition of protein synthesis is the process which might be closest to the primary target of OTA."}
{"id": "PMID:205335", "title": "Metastatic cystosarcoma phyllodes. A report of 2 cases presenting with neurological symptoms.", "content": "Two cases of cystosarcoma phyllodes of the breast are presented with central nervous system (CNS) metastases appearing several years after mastectomy for the primary lesion. Unusual features in these cases include the widespread metastases themselves, neurologic symptomatology and CNS involvement, metastases into a uterine leiomyoma and into an area of hepatic adenomatous hyperplasia, and glomus-like structures in one of the primaries with similar structures resembling glomus cells in metastases. The distant metastases were of stromal cells only and frequently surrounded epithelial cells to isolate the indigenous glandular structures. The concept that cytosarcoma is a peculiar stromal neoplasm rather than a tumor of dual neoplastic origin is discussed.", "contents": "Metastatic cystosarcoma phyllodes. A report of 2 cases presenting with neurological symptoms. Two cases of cystosarcoma phyllodes of the breast are presented with central nervous system (CNS) metastases appearing several years after mastectomy for the primary lesion. Unusual features in these cases include the widespread metastases themselves, neurologic symptomatology and CNS involvement, metastases into a uterine leiomyoma and into an area of hepatic adenomatous hyperplasia, and glomus-like structures in one of the primaries with similar structures resembling glomus cells in metastases. The distant metastases were of stromal cells only and frequently surrounded epithelial cells to isolate the indigenous glandular structures. The concept that cytosarcoma is a peculiar stromal neoplasm rather than a tumor of dual neoplastic origin is discussed."}
{"id": "PMID:205336", "title": "Histologic grading of Wilms' tumor as potential prognostic factor: results of a retrospective study of 26 patients.", "content": "A histologic grading system based on tumor differentiation was applied in a retrospective study of 26 patients with Wilms' tumor to determine if it might provide an index to prognosis. The results were compared to those obtained by applying a histologic classification based on the presence or absence of individual histologic structures to the same tumors. Low grade tumors with predominance of differentiated structures--glomeruli and tubules--were associated with a better cure rate than high grade tumors composed mainly of undifferentiated spindle elements. The presence of undifferentiated large cells correlated with poor cure rate. The findings suggest that histologic grading may be valid as a prognostic factor in Wilms' tumor.", "contents": "Histologic grading of Wilms' tumor as potential prognostic factor: results of a retrospective study of 26 patients. A histologic grading system based on tumor differentiation was applied in a retrospective study of 26 patients with Wilms' tumor to determine if it might provide an index to prognosis. The results were compared to those obtained by applying a histologic classification based on the presence or absence of individual histologic structures to the same tumors. Low grade tumors with predominance of differentiated structures--glomeruli and tubules--were associated with a better cure rate than high grade tumors composed mainly of undifferentiated spindle elements. The presence of undifferentiated large cells correlated with poor cure rate. The findings suggest that histologic grading may be valid as a prognostic factor in Wilms' tumor."}
{"id": "PMID:205337", "title": "An immunologic basis for detection of occult primary malignancies of the head and neck.", "content": "After extensive evaluation of patients with metastatic neck disease and clinically undetectable primary cancer of the head and neck, the clinician is often faced with the difficult question of subsequent management. In this study, sera from 11 patients with clinically occult carcinoma and metastatic lymphadenopathy were studied for Epstein-Barr virus-associated antigens. These were compared with 35 sera from patients with known nasopharyngeal carcinoma at all stages of disease and treatment and with 212 sera from control patients with other head and neck tumors, patients with lymphoma, and normal controls. There was a significant correlation between high antibody titers to Epstein-Barr virus, especially in the serum IgA fraction, and the presence of nasopharyngeal carcinoma. Thus, identification of occult nasopharyngeal carcinoma by immunologic means may have important application in the selective management of the patient with an unknown head and neck primary malignancy.", "contents": "An immunologic basis for detection of occult primary malignancies of the head and neck. After extensive evaluation of patients with metastatic neck disease and clinically undetectable primary cancer of the head and neck, the clinician is often faced with the difficult question of subsequent management. In this study, sera from 11 patients with clinically occult carcinoma and metastatic lymphadenopathy were studied for Epstein-Barr virus-associated antigens. These were compared with 35 sera from patients with known nasopharyngeal carcinoma at all stages of disease and treatment and with 212 sera from control patients with other head and neck tumors, patients with lymphoma, and normal controls. There was a significant correlation between high antibody titers to Epstein-Barr virus, especially in the serum IgA fraction, and the presence of nasopharyngeal carcinoma. Thus, identification of occult nasopharyngeal carcinoma by immunologic means may have important application in the selective management of the patient with an unknown head and neck primary malignancy."}
{"id": "PMID:205338", "title": "Hepatic artery ligation and adriamycin infusion chemotherapy for hepatoma.", "content": "Two patients with hepatoma of the liver were treated with ligation of the hepatic artery and continuous infusion of adriamycin into the distal arterial branch. Both patients had tumor replacing 60-75% of the normal liver parenchyma. There was clinical improvement and objective shrinkage of the tumor by liver scan lasting for 5 and 7 months. But both cases died 7 and 11 months later, probably of cardiac toxicity (total dose of adriamycin = 500 mg/m2).", "contents": "Hepatic artery ligation and adriamycin infusion chemotherapy for hepatoma. Two patients with hepatoma of the liver were treated with ligation of the hepatic artery and continuous infusion of adriamycin into the distal arterial branch. Both patients had tumor replacing 60-75% of the normal liver parenchyma. There was clinical improvement and objective shrinkage of the tumor by liver scan lasting for 5 and 7 months. But both cases died 7 and 11 months later, probably of cardiac toxicity (total dose of adriamycin = 500 mg/m2)."}
{"id": "PMID:205339", "title": "Inflammatory fibrous histiocytoma: case report.", "content": "This report concerns a patient with inflammatory fibrous histiocytoma, who in contrast to previous reported cases, has had a long survival (20 years), without evidence of recurrent disease following treatment. An interesting but nonreproducible study was the development of leukemia in 2 of 3 Swiss strain mice following the intraperitoneal injection of a saline extract of the patient's tumor.", "contents": "Inflammatory fibrous histiocytoma: case report. This report concerns a patient with inflammatory fibrous histiocytoma, who in contrast to previous reported cases, has had a long survival (20 years), without evidence of recurrent disease following treatment. An interesting but nonreproducible study was the development of leukemia in 2 of 3 Swiss strain mice following the intraperitoneal injection of a saline extract of the patient's tumor."}
{"id": "PMID:205340", "title": "Wilms' tumor: prognostic factors for patients without metastases at diagnosis: results of the National Wilms' Tumor Study.", "content": "Multivariate statistical analyses are used to evaluate a wide range of factors in predicting relapse and survival for 429 children enrolled in the National Wilms' Tumor Study. Anaplastic or sarcomatous histology, specimen weight over 250 grams, positive regional lymph nodes, treatment with only a single drug and age over two years are the most important predictors of relapse. The first three factors also predict mortality. Laterality, capsular penetration, intrarenal vascular invasion, direct regional extension and operative spillage have lesser effects which do not contribute significantly to the multivariate prediction equations, while sex, race and the presence of a tumor thrombus in the renal vein have essentially no effect. Treatment with combination chemotherapy is confirmed to be efficacious regardless of what prognostic factors are operating. A statistical model allows prediction of relapse and death for each of 24 patient subgroups, with the estimates of percentage relapsed ranging from 3% to 100%.", "contents": "Wilms' tumor: prognostic factors for patients without metastases at diagnosis: results of the National Wilms' Tumor Study. Multivariate statistical analyses are used to evaluate a wide range of factors in predicting relapse and survival for 429 children enrolled in the National Wilms' Tumor Study. Anaplastic or sarcomatous histology, specimen weight over 250 grams, positive regional lymph nodes, treatment with only a single drug and age over two years are the most important predictors of relapse. The first three factors also predict mortality. Laterality, capsular penetration, intrarenal vascular invasion, direct regional extension and operative spillage have lesser effects which do not contribute significantly to the multivariate prediction equations, while sex, race and the presence of a tumor thrombus in the renal vein have essentially no effect. Treatment with combination chemotherapy is confirmed to be efficacious regardless of what prognostic factors are operating. A statistical model allows prediction of relapse and death for each of 24 patient subgroups, with the estimates of percentage relapsed ranging from 3% to 100%."}
{"id": "PMID:205341", "title": "Ocular granulocytic sarcoma (chloroma) with acute myelomonocytic leukemia in Turkish children.", "content": "In a series of 166 leukemic children from Turkey, 56 had acute myelomonocytic leukemia (AMML). Seventeen boys and 3 girls presented with chloroma-like deposits (granulocytic or myeloid sarcomas) in the eye and orbit, all showing AMML on initial study of blood and marrow. The ocular lesions responded rapidly to antileukemic therapy. Laboratory studies of AMML cases revealed no cytogenetic or immune defects, and Epstein-Barr virus titers were normal. A group-specific (GS-3) antigen (type-C virus?) was identified in one patient by radioimmunoassay of orbital tumor extracts. It is not clear what factors contribute toward the myelomoncytic differentiation of leukemia and its localization in the eye and orbit, but opportunities for further study are enhanced by reports of a predisposition to ocular chloroma among leukemic children in Africa, Egypt, and Japan.", "contents": "Ocular granulocytic sarcoma (chloroma) with acute myelomonocytic leukemia in Turkish children. In a series of 166 leukemic children from Turkey, 56 had acute myelomonocytic leukemia (AMML). Seventeen boys and 3 girls presented with chloroma-like deposits (granulocytic or myeloid sarcomas) in the eye and orbit, all showing AMML on initial study of blood and marrow. The ocular lesions responded rapidly to antileukemic therapy. Laboratory studies of AMML cases revealed no cytogenetic or immune defects, and Epstein-Barr virus titers were normal. A group-specific (GS-3) antigen (type-C virus?) was identified in one patient by radioimmunoassay of orbital tumor extracts. It is not clear what factors contribute toward the myelomoncytic differentiation of leukemia and its localization in the eye and orbit, but opportunities for further study are enhanced by reports of a predisposition to ocular chloroma among leukemic children in Africa, Egypt, and Japan."}
{"id": "PMID:205342", "title": "Abrogation of tumor rejection by trypan blue.", "content": "Trypan blue treatment prevented tumor-specific rejection in three animal model systems. These included the spontaneous rejection of tumors of mice (UVT-2051) and guinea pig (line 1 hepatoma) as well as vaccine-induced rejection of a guinea pig tumor (line 10 hepatoma). Secondary immune reactions to line 10 cell challenges were not abolished by trypan blue treatment. Although trypan blue is a potent inhibitor of macrophage cytotoxicity in vitro, the mechanism by which it inhibited tumor-specific rejection has not been established.", "contents": "Abrogation of tumor rejection by trypan blue. Trypan blue treatment prevented tumor-specific rejection in three animal model systems. These included the spontaneous rejection of tumors of mice (UVT-2051) and guinea pig (line 1 hepatoma) as well as vaccine-induced rejection of a guinea pig tumor (line 10 hepatoma). Secondary immune reactions to line 10 cell challenges were not abolished by trypan blue treatment. Although trypan blue is a potent inhibitor of macrophage cytotoxicity in vitro, the mechanism by which it inhibited tumor-specific rejection has not been established."}
{"id": "PMID:205344", "title": "Chromatin-associated glycoproteins of normal rat liver and Novikoff hepatoma ascites cells.", "content": "Glycoproteins were demonstrated in the 0.6 M NaCl extract of chromatin of normal liver and Novikoff hepatoma cells by periodic acid-Schiff staining of sodium dodecyl sulfate-polyacrylamide gels. In chromatin extracts of Novikoff hepatoma cells, six major periodic acid-Schiff-positive bands coincident with Coomassie Blue-stained protein bands were found with molecular weights of 30,000, 54,000, 64,000, 75,000, 104,000, and 127,000. A corresponding extract from normal rat liver chromatin revealed the presence of four major periodic acid-Schiff-positive bands that migrated with protein bands at molecular weights of 16,000, 30,000, 54,000, and 75,000. The glycoproteins of these extracts contained either mannose or alpha-D-glucose, fucose, and N-acetylglucosamine as shown by the specificity of lectins in affinoelectrophoresis. One of the glycoproteins detected by affinoelectrophoresis was very basic.", "contents": "Chromatin-associated glycoproteins of normal rat liver and Novikoff hepatoma ascites cells. Glycoproteins were demonstrated in the 0.6 M NaCl extract of chromatin of normal liver and Novikoff hepatoma cells by periodic acid-Schiff staining of sodium dodecyl sulfate-polyacrylamide gels. In chromatin extracts of Novikoff hepatoma cells, six major periodic acid-Schiff-positive bands coincident with Coomassie Blue-stained protein bands were found with molecular weights of 30,000, 54,000, 64,000, 75,000, 104,000, and 127,000. A corresponding extract from normal rat liver chromatin revealed the presence of four major periodic acid-Schiff-positive bands that migrated with protein bands at molecular weights of 16,000, 30,000, 54,000, and 75,000. The glycoproteins of these extracts contained either mannose or alpha-D-glucose, fucose, and N-acetylglucosamine as shown by the specificity of lectins in affinoelectrophoresis. One of the glycoproteins detected by affinoelectrophoresis was very basic."}
{"id": "PMID:205345", "title": "Production of plasminogen activator by cells transformed by herpesviruses.", "content": "Plasminogen activator is produced by hamster cells transformed by human herpesviruses. These cell lines have previously been shown to be oncogenic when injected s.c. into newborn syngeneic hamsters. Lysis of fibrin overlays by these cell lines was plasminogen dependent. Normal hamster embryo fibroblasts and a hamster cell line transformed by PARA-7 (an adenovirus-SV 40 hybrid) failed to produced lysis. In separate experiments fibrin overlay of lytically infected secondary rabbit kidney cells did not show induction of this activity during the normal course of productive infection. The human cell line TE-85 clone F-5, a clonal cell line from a human osteogenic sarcoma, failed to produce plasminogen activator, but two separate clones of these cells that were morphologically transformed after exposure to UV-inactivated herpes simplex virus type 2 produced rapid lysis of the fibrin overlay. Clonal variation was observed in herpes simplex virus types 1 and 2-transformed hamster lines and is under investigation. It is suggested that plasminogen activator detection may serve as a convenient assay system for transformation of normal cells by herpesviruses.", "contents": "Production of plasminogen activator by cells transformed by herpesviruses. Plasminogen activator is produced by hamster cells transformed by human herpesviruses. These cell lines have previously been shown to be oncogenic when injected s.c. into newborn syngeneic hamsters. Lysis of fibrin overlays by these cell lines was plasminogen dependent. Normal hamster embryo fibroblasts and a hamster cell line transformed by PARA-7 (an adenovirus-SV 40 hybrid) failed to produced lysis. In separate experiments fibrin overlay of lytically infected secondary rabbit kidney cells did not show induction of this activity during the normal course of productive infection. The human cell line TE-85 clone F-5, a clonal cell line from a human osteogenic sarcoma, failed to produce plasminogen activator, but two separate clones of these cells that were morphologically transformed after exposure to UV-inactivated herpes simplex virus type 2 produced rapid lysis of the fibrin overlay. Clonal variation was observed in herpes simplex virus types 1 and 2-transformed hamster lines and is under investigation. It is suggested that plasminogen activator detection may serve as a convenient assay system for transformation of normal cells by herpesviruses."}
{"id": "PMID:205346", "title": "Marked stimulation of lymphocyte-mediated attack on tumor cells by target-directed liposomes containing immune RNA.", "content": "A marked stimulation of normal guinea pig lymphocytes was obtained by incubating them with liposomes that contained both antibody to lymphocytes to provide \"homing\" of the vesicles and immune RNA isolated from guinea pigs immunized with syngeneic line 10 hepatocarcinoma cells. Tumor cell cytotoxicity was monitored by a 51Cr release assay. This target cell delivery of immune RNA by liposomes produced a dose-dependent stimulation up to 12 times that achieved by in vitro methods with naked immune RNA.", "contents": "Marked stimulation of lymphocyte-mediated attack on tumor cells by target-directed liposomes containing immune RNA. A marked stimulation of normal guinea pig lymphocytes was obtained by incubating them with liposomes that contained both antibody to lymphocytes to provide \"homing\" of the vesicles and immune RNA isolated from guinea pigs immunized with syngeneic line 10 hepatocarcinoma cells. Tumor cell cytotoxicity was monitored by a 51Cr release assay. This target cell delivery of immune RNA by liposomes produced a dose-dependent stimulation up to 12 times that achieved by in vitro methods with naked immune RNA."}
{"id": "PMID:205348", "title": "Electron microscopic studies of intracisternal virus particles in Soehner-Dmochowski murine sarcoma virus-induced bone tumors of New Zealand Black rats.", "content": "Soehner-Dmochowski murine sarcoma virus (Moloney)-induced bone tumors of New Zealand Black rats carry two morphologically different types of virus particles, namely, extracellular type C and intracisternal virus particles, which have thus far not been reported. These two types of virus particles have also been observed in the tissue culture cells derived from normal prostate tissues of A/Dm and BALB/c/Dm mice after inoculation of cell-free extracts of these bone tumors. The intracisternal virus particles, 90 to 120 nm in diameter, have always been found in the rough endoplasmic reticulum; they have two inner concentric layers with a relatively electron-lucent center, frequently showing cylindrical, chain-like, or multipolar budding forms. Type C virus particles produced by Soehner-Dmochowski murine sarcoma virus (Moloney)-infected prostate tissue culture cells from A/Dm and BALB/c/Dm mice belong to the murine sarcoma-murine leukemia virus group, as revealed by the fixed immunofluorescence test and by immunoelectron microscopy. The morphological and immunological relationship of intracisternal virus particles and other types of virus particles (such as type C, type H, and intracisternal type A virus particles) and intracisternal virus particles in guinea pig leukemia are defined by routine electron microscopy observations and by immunoelectron microscopy studies.", "contents": "Electron microscopic studies of intracisternal virus particles in Soehner-Dmochowski murine sarcoma virus-induced bone tumors of New Zealand Black rats. Soehner-Dmochowski murine sarcoma virus (Moloney)-induced bone tumors of New Zealand Black rats carry two morphologically different types of virus particles, namely, extracellular type C and intracisternal virus particles, which have thus far not been reported. These two types of virus particles have also been observed in the tissue culture cells derived from normal prostate tissues of A/Dm and BALB/c/Dm mice after inoculation of cell-free extracts of these bone tumors. The intracisternal virus particles, 90 to 120 nm in diameter, have always been found in the rough endoplasmic reticulum; they have two inner concentric layers with a relatively electron-lucent center, frequently showing cylindrical, chain-like, or multipolar budding forms. Type C virus particles produced by Soehner-Dmochowski murine sarcoma virus (Moloney)-infected prostate tissue culture cells from A/Dm and BALB/c/Dm mice belong to the murine sarcoma-murine leukemia virus group, as revealed by the fixed immunofluorescence test and by immunoelectron microscopy. The morphological and immunological relationship of intracisternal virus particles and other types of virus particles (such as type C, type H, and intracisternal type A virus particles) and intracisternal virus particles in guinea pig leukemia are defined by routine electron microscopy observations and by immunoelectron microscopy studies."}
{"id": "PMID:205350", "title": "Prevalence of non-T-cells in the replication of the N-tropic, type C virus of young AKR mice.", "content": "The XC infectious center assay was used to study the nature of the lymphoid cells producing N-tropic C-type viruses in preleukemic AKR mice. Viral production by thymic cell suspensions was very low and was possibly due to contaminating cells. Production at least 100-fold higher was found in spleen cells and was probably due to non-T-cells. The significance of these results is discussed briefly, including the possibility that the N-tropic XC syncitia-inducing type C virus of young AKR mice is not the leukemogenic agent.", "contents": "Prevalence of non-T-cells in the replication of the N-tropic, type C virus of young AKR mice. The XC infectious center assay was used to study the nature of the lymphoid cells producing N-tropic C-type viruses in preleukemic AKR mice. Viral production by thymic cell suspensions was very low and was possibly due to contaminating cells. Production at least 100-fold higher was found in spleen cells and was probably due to non-T-cells. The significance of these results is discussed briefly, including the possibility that the N-tropic XC syncitia-inducing type C virus of young AKR mice is not the leukemogenic agent."}
{"id": "PMID:205351", "title": "Abnormal distribution of O-alkyl groups in the neutral glycerolipids from human hepatocellular carcinomas.", "content": "The direct comparison of O-alkylglycerol composition in the neutral lipids fractions prepared from human hepatocellular carcinomas with that in corresponding preparations from nonneoplastic liver is reported. Tumor-bearing liver and noncancerous liver specimens were obtained either during surgery or at autopsy. Thirty different tissue specimens obtained from 18 cases were analyzed. Representative samples from each specimen were examined microscopically to confirm the pathological diagnosis. Gas chromatographic analysis of alkylglycerol derivatives showed that hexadecylglycerol, octadecylglycerol, and octadecenylglycerol were the principal components. Compared to the noncancerous liver, hepatocellular carcinomas contained higher proportions of hexadecylglycerol and lower proportions of both C18-glyceryl ethers. Associated with this change was an increase in the proportion of saturated to monoenic alkylglycerols. These abnormalities appeared to be more severe in the necrotic areas of the tumors. Higher concentrations of neutral alkyl glycerolipids and of cholesterol were found in the tumors; no differences between the two groups could be found in the levels of ether-linked phosphoglycerides, triglycerides, and lipid phosphorus.", "contents": "Abnormal distribution of O-alkyl groups in the neutral glycerolipids from human hepatocellular carcinomas. The direct comparison of O-alkylglycerol composition in the neutral lipids fractions prepared from human hepatocellular carcinomas with that in corresponding preparations from nonneoplastic liver is reported. Tumor-bearing liver and noncancerous liver specimens were obtained either during surgery or at autopsy. Thirty different tissue specimens obtained from 18 cases were analyzed. Representative samples from each specimen were examined microscopically to confirm the pathological diagnosis. Gas chromatographic analysis of alkylglycerol derivatives showed that hexadecylglycerol, octadecylglycerol, and octadecenylglycerol were the principal components. Compared to the noncancerous liver, hepatocellular carcinomas contained higher proportions of hexadecylglycerol and lower proportions of both C18-glyceryl ethers. Associated with this change was an increase in the proportion of saturated to monoenic alkylglycerols. These abnormalities appeared to be more severe in the necrotic areas of the tumors. Higher concentrations of neutral alkyl glycerolipids and of cholesterol were found in the tumors; no differences between the two groups could be found in the levels of ether-linked phosphoglycerides, triglycerides, and lipid phosphorus."}
{"id": "PMID:205353", "title": "Induction of sister chromatid exchanges by transformation with simian virus 40.", "content": "The frequency of sister chromatid exchange (SCE) has been followed sequentially after the addition of SV40 to human diploid fibroblast cultures. The SCE frequency was nearly the same in uninfected controls and in infected cultures before they became tumor antigen positive. When cells exhibited tumor antigen, the SCE frequency increased over a wide range, and changes in chromosome number and structure were observed simultaneously. Cells with induced chromosome abnormalities without increased SCE's and the reverse present the possibility that the two phenomena have different viral mechanisms. This increase in SCE can be added to the previously demonstrated change in chromosome number and increase in chromosome breakage and rearrangement as indicators of genetic damage associated with viral transformation.", "contents": "Induction of sister chromatid exchanges by transformation with simian virus 40. The frequency of sister chromatid exchange (SCE) has been followed sequentially after the addition of SV40 to human diploid fibroblast cultures. The SCE frequency was nearly the same in uninfected controls and in infected cultures before they became tumor antigen positive. When cells exhibited tumor antigen, the SCE frequency increased over a wide range, and changes in chromosome number and structure were observed simultaneously. Cells with induced chromosome abnormalities without increased SCE's and the reverse present the possibility that the two phenomena have different viral mechanisms. This increase in SCE can be added to the previously demonstrated change in chromosome number and increase in chromosome breakage and rearrangement as indicators of genetic damage associated with viral transformation."}
{"id": "PMID:205354", "title": "An epithelial cell line with chronic polyoma infection established from a spontaneous mouse pancreatic adenocarcinoma.", "content": "The establishment of an epithelial cell line from a mouse pancreatic adenocarcinoma is described. The cell line, designated LTPA, was aneuploid and exhibited many transformed growth properties (rapid growth rate, failure to show density-dependent inhibition of growth, ability to grow in defined medium). A type C oncornavirus was isolated from the culture medium, and electron microscopy also revealed the presence of intracisternal type A particles. LTPA cells carried a persistent polyoma infection which produced only low levels of cytopathic effects. A mycoplasmal contamination was also carried. When injected s.c. into Swiss nu/nu mice, LTPA cells formed ductular structures which were destroyed by inflammatory reactions within 3 weeks.", "contents": "An epithelial cell line with chronic polyoma infection established from a spontaneous mouse pancreatic adenocarcinoma. The establishment of an epithelial cell line from a mouse pancreatic adenocarcinoma is described. The cell line, designated LTPA, was aneuploid and exhibited many transformed growth properties (rapid growth rate, failure to show density-dependent inhibition of growth, ability to grow in defined medium). A type C oncornavirus was isolated from the culture medium, and electron microscopy also revealed the presence of intracisternal type A particles. LTPA cells carried a persistent polyoma infection which produced only low levels of cytopathic effects. A mycoplasmal contamination was also carried. When injected s.c. into Swiss nu/nu mice, LTPA cells formed ductular structures which were destroyed by inflammatory reactions within 3 weeks."}
{"id": "PMID:205356", "title": "Increased susceptibility to feline leukemia virus infection in cats exposed to methylnitrosourea.", "content": "Exposure of adult specific-pathogen-free cats to methylnitrosourea resulted in increased susceptibility to infection by feline leukemia virus. A greater proportion of cats exposed to methylnitrosourea and feline leukemia virus (69%) became persistently viremic than those exposed to feline leukemia virus alone (17%). Segmented neutrophils were reduced by 90 to 99% within 3 days following exposure to methylnitrosourea, (15 to 20 mg/kg) whereas the effects on lymphocytes and erythrocytes, although less obvious, were also detected.", "contents": "Increased susceptibility to feline leukemia virus infection in cats exposed to methylnitrosourea. Exposure of adult specific-pathogen-free cats to methylnitrosourea resulted in increased susceptibility to infection by feline leukemia virus. A greater proportion of cats exposed to methylnitrosourea and feline leukemia virus (69%) became persistently viremic than those exposed to feline leukemia virus alone (17%). Segmented neutrophils were reduced by 90 to 99% within 3 days following exposure to methylnitrosourea, (15 to 20 mg/kg) whereas the effects on lymphocytes and erythrocytes, although less obvious, were also detected."}
{"id": "PMID:205357", "title": "Growth of transplanted rat tumors following administration of cell-free tumor antigens.", "content": "The variable effect of immunizations with cell-free tumor extract (TE) in a weakly antigenic (Morris hepatoma 3924a) and a highly antigenic (glioma 9L) inbred rat model system was described. Tumor enhancement was noted with the weakly antigenic tumor following either immunization with a low dose of TE admixed with Freund's adjuvant or immunization with high doses of TE. Enhancement was observed at four tumor cell challenge levels. Tumor enhancement with the highly antigenic tumor was found at only one level and was seen following immunization with intermediate doses of TE and a high tumor cell challenge. Tumor protection was only detected with the weakly antigenic tumor following immunizations with an intermediate dose of TE and challenge with a tumor cell dose 5-fold over threshold. This protection was tumor specific, as judged by an amputation and rechallenge experiment.", "contents": "Growth of transplanted rat tumors following administration of cell-free tumor antigens. The variable effect of immunizations with cell-free tumor extract (TE) in a weakly antigenic (Morris hepatoma 3924a) and a highly antigenic (glioma 9L) inbred rat model system was described. Tumor enhancement was noted with the weakly antigenic tumor following either immunization with a low dose of TE admixed with Freund's adjuvant or immunization with high doses of TE. Enhancement was observed at four tumor cell challenge levels. Tumor enhancement with the highly antigenic tumor was found at only one level and was seen following immunization with intermediate doses of TE and a high tumor cell challenge. Tumor protection was only detected with the weakly antigenic tumor following immunizations with an intermediate dose of TE and challenge with a tumor cell dose 5-fold over threshold. This protection was tumor specific, as judged by an amputation and rechallenge experiment."}
{"id": "PMID:205359", "title": "Calcium requirements for the proliferation of cells infected with a temperature-sensitive mutant of Rous sarcoma virus.", "content": "Between 32 degrees and 39 degrees, uninfected normal rat kidney (NRK) cells proliferated minimally, or not at all, in medium containing 0 to 0.01 mM extracellular free calcium. Transformation of NRK cells by wild-type avian sarcoma virus B77 enabled them to proliferate equally rapidly at all temperatures in high (1.25 mM)- or low (0.001 mM-calcium medium. Transformation by the temperature-sensitive LA-23 mutant of Rous sarcoma virus also enabled NRK cells to proliferate in low (0.001 mM)-calcium medium at 32 degrees or 37 degrees. However, the LA-23 NRK cells could not proliferate in low (0.001 mM)-calcium medium at a nonpermissive temperature such as 39 degrees, which prevents expression of other aspects of the transformed phenotype.", "contents": "Calcium requirements for the proliferation of cells infected with a temperature-sensitive mutant of Rous sarcoma virus. Between 32 degrees and 39 degrees, uninfected normal rat kidney (NRK) cells proliferated minimally, or not at all, in medium containing 0 to 0.01 mM extracellular free calcium. Transformation of NRK cells by wild-type avian sarcoma virus B77 enabled them to proliferate equally rapidly at all temperatures in high (1.25 mM)- or low (0.001 mM-calcium medium. Transformation by the temperature-sensitive LA-23 mutant of Rous sarcoma virus also enabled NRK cells to proliferate in low (0.001 mM)-calcium medium at 32 degrees or 37 degrees. However, the LA-23 NRK cells could not proliferate in low (0.001 mM)-calcium medium at a nonpermissive temperature such as 39 degrees, which prevents expression of other aspects of the transformed phenotype."}
{"id": "PMID:205361", "title": "Intratumor chemoimmunotherapy with mitomycin C and components from mycobacteria in regression of line 10 tumors in guinea pigs.", "content": "Intratumor chemotherapy with the use of mitomycin C and/or immunotherapy caused regression of line 10 carcinomas in strain 2 guinea pigs and resulted in development of tumor-specific immunity. The immunotherapeutic preparation consisted of oil-in-water emulsions containing Mycobacterium cell walls or residues of cell walls termed cell wall skeletons. The latter preparations were combined with trehalose dimycolate, which was isolated by microparticulate chromatography from whole cells of mycobacteria. Reducing mitomycin C to a single intratumor injection of 50 microgram produced little necrotizing effect and a mean tumor regression rate of 17%. Intratumor immunotherapy 1 day after treatment with 50 microgram of mitomycin C resulted in regression of 90% of the treated tumors as compared to mean regression rates of 30 to 50% for immunotherapy alone. In addition, chemoimmunotherapy was more effective than either chemotherapy or immunotherapy alone in producing regression of relatively large, as well as smaller, tumors.", "contents": "Intratumor chemoimmunotherapy with mitomycin C and components from mycobacteria in regression of line 10 tumors in guinea pigs. Intratumor chemotherapy with the use of mitomycin C and/or immunotherapy caused regression of line 10 carcinomas in strain 2 guinea pigs and resulted in development of tumor-specific immunity. The immunotherapeutic preparation consisted of oil-in-water emulsions containing Mycobacterium cell walls or residues of cell walls termed cell wall skeletons. The latter preparations were combined with trehalose dimycolate, which was isolated by microparticulate chromatography from whole cells of mycobacteria. Reducing mitomycin C to a single intratumor injection of 50 microgram produced little necrotizing effect and a mean tumor regression rate of 17%. Intratumor immunotherapy 1 day after treatment with 50 microgram of mitomycin C resulted in regression of 90% of the treated tumors as compared to mean regression rates of 30 to 50% for immunotherapy alone. In addition, chemoimmunotherapy was more effective than either chemotherapy or immunotherapy alone in producing regression of relatively large, as well as smaller, tumors."}
{"id": "PMID:205362", "title": "Activities of key gluconeogenic enzymes and glycogen synthase in rat and human livers, hepatomas, and hepatoma cell cultures.", "content": "The activities of pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and glycogen synthetase (GS) were determined in the cancerous and in the apparently uninvolved (host) regions of livers from primary hepatoma patients as well as in normal adult human livers and human fetal livers. The activities of these enzymes were also assayed in a fairly fast-growing, 3'-methyl-4-dimethylaminoazobenzene-induced transplantable rat hepatoma and in hepatoma cell lines derived from both rat and human tumors. In the human hepatoma, as in the rat hepatoma, the activities of PC, PEPCK, and G6Pase were considerably reduced, compared to those in the host liver. The activities of both the a (glucose 6-phosphate-independent) and b (glucose 6-phosphate-dependent) forms of GS were also lower in human and rat hepatomas than in the respective host livers. Activities of PC, PEPCK, and G6Pase in the human hepatomas were often comparable with those of fetal livers. In rat and human hepatoma cells, the activities of PC, PEPCK, and G6Pase were similar to or lower than the activities in the respective hepatomas; the activities of GS a were also similar to those in the hepatoma, whereas the activities of GS b were somewhat higher.", "contents": "Activities of key gluconeogenic enzymes and glycogen synthase in rat and human livers, hepatomas, and hepatoma cell cultures. The activities of pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and glycogen synthetase (GS) were determined in the cancerous and in the apparently uninvolved (host) regions of livers from primary hepatoma patients as well as in normal adult human livers and human fetal livers. The activities of these enzymes were also assayed in a fairly fast-growing, 3'-methyl-4-dimethylaminoazobenzene-induced transplantable rat hepatoma and in hepatoma cell lines derived from both rat and human tumors. In the human hepatoma, as in the rat hepatoma, the activities of PC, PEPCK, and G6Pase were considerably reduced, compared to those in the host liver. The activities of both the a (glucose 6-phosphate-independent) and b (glucose 6-phosphate-dependent) forms of GS were also lower in human and rat hepatomas than in the respective host livers. Activities of PC, PEPCK, and G6Pase in the human hepatomas were often comparable with those of fetal livers. In rat and human hepatoma cells, the activities of PC, PEPCK, and G6Pase were similar to or lower than the activities in the respective hepatomas; the activities of GS a were also similar to those in the hepatoma, whereas the activities of GS b were somewhat higher."}
{"id": "PMID:205364", "title": "Alteration of sodium transport in mouse mammary epithelium associated with neoplastic transformation.", "content": "Using electrophysiological techniques we have examined the apical membrane ionic permeabilities of primary cell cultures of the mouse mammary gland in the midpregnant, preneoplastic, and neoplastic states. Membrane Na+ permeability changed with tumorigenesis, whereas K+ and Cl- permeabilities were unaltered. With tracer flux techniques the unidirectional efflux rate constant of 22Na was found to be greater in tumor cells than it is in normal cells. This increase in 22Na efflux was eliminated by the addition of ouabain. The results are interpreted as an increase in Na+ permeability and in Na+-K+-ATPase activity with the neoplastic transformation. The presence or absence of the virus in midpregnant cells does not seem to affect Na+ permeability.", "contents": "Alteration of sodium transport in mouse mammary epithelium associated with neoplastic transformation. Using electrophysiological techniques we have examined the apical membrane ionic permeabilities of primary cell cultures of the mouse mammary gland in the midpregnant, preneoplastic, and neoplastic states. Membrane Na+ permeability changed with tumorigenesis, whereas K+ and Cl- permeabilities were unaltered. With tracer flux techniques the unidirectional efflux rate constant of 22Na was found to be greater in tumor cells than it is in normal cells. This increase in 22Na efflux was eliminated by the addition of ouabain. The results are interpreted as an increase in Na+ permeability and in Na+-K+-ATPase activity with the neoplastic transformation. The presence or absence of the virus in midpregnant cells does not seem to affect Na+ permeability."}
{"id": "PMID:205365", "title": "Characterization of a unique cell line (LAZ 221) from human acute lymphocytic (\"null\" cell) leukemia.", "content": "A unique human cell line designated LAZ 221 has been established from the peripheral blood of a patient with acute lymphocytic leukemia of the \"null\" cell type. The cell line does not possess the Epstein-Barr virus nuclear antigen and has a karyotype of 45,XX,-9,-12,+(9q12q). Both the established cell line and the patient's uncultured blast cells share the same phenotypic markers. They both lack T-cell markers. They fail to form sheep erythrocyte rosettes and do not react with T-cell-specific antisera (TH1-, HTL-), nor do they possess B-cell markers. They do not form rosettes with erythrocytes sensitized with complement, and they are surface immunoglobulin negative. However, they do possess an HLA-D-related glycoprotein complex of 23,000 to 30,000 daltons, an la-like antigen. Thus, LAZ 221 shares the phenotype of the patient's uncultured blasts and is a cell line representative of about 75% of all human acute lymphocytic leukemias. In this respect it differs from previously described human hematopoietic cell lines.", "contents": "Characterization of a unique cell line (LAZ 221) from human acute lymphocytic (\"null\" cell) leukemia. A unique human cell line designated LAZ 221 has been established from the peripheral blood of a patient with acute lymphocytic leukemia of the \"null\" cell type. The cell line does not possess the Epstein-Barr virus nuclear antigen and has a karyotype of 45,XX,-9,-12,+(9q12q). Both the established cell line and the patient's uncultured blast cells share the same phenotypic markers. They both lack T-cell markers. They fail to form sheep erythrocyte rosettes and do not react with T-cell-specific antisera (TH1-, HTL-), nor do they possess B-cell markers. They do not form rosettes with erythrocytes sensitized with complement, and they are surface immunoglobulin negative. However, they do possess an HLA-D-related glycoprotein complex of 23,000 to 30,000 daltons, an la-like antigen. Thus, LAZ 221 shares the phenotype of the patient's uncultured blasts and is a cell line representative of about 75% of all human acute lymphocytic leukemias. In this respect it differs from previously described human hematopoietic cell lines."}
{"id": "PMID:205366", "title": "Immunization of mice against murine mammary tumor virus infection and mammary tumor development.", "content": "Formalin-inactivated whole murine mammary tumor virus (MuMTV), VuMTV membranes, the acid-soluble component of MuMTV, and purified MuMTV glycoprotein with a molecular weight of 55,000 (gp55; also designated as gp52) were used as vaccines in an attempt to identify the MuMTV antigen(s) that can protect mice from exogenous MuMTV infection and subsequent tumor development. Formalin-inactivated whole MuMTV, MuMTV membranes, and purified MuMTV gp55 were effective immunogens, whereas the acid-soluble component of MuMTV (which consists mainly of MuMTV gp55) failed to protect mice from challenge with live virus. These results suggest that (a) MuMTV gp55 is the major immunizing antigen and (b) its native conformation must be maintained for it to be an effective vaccine.", "contents": "Immunization of mice against murine mammary tumor virus infection and mammary tumor development. Formalin-inactivated whole murine mammary tumor virus (MuMTV), VuMTV membranes, the acid-soluble component of MuMTV, and purified MuMTV glycoprotein with a molecular weight of 55,000 (gp55; also designated as gp52) were used as vaccines in an attempt to identify the MuMTV antigen(s) that can protect mice from exogenous MuMTV infection and subsequent tumor development. Formalin-inactivated whole MuMTV, MuMTV membranes, and purified MuMTV gp55 were effective immunogens, whereas the acid-soluble component of MuMTV (which consists mainly of MuMTV gp55) failed to protect mice from challenge with live virus. These results suggest that (a) MuMTV gp55 is the major immunizing antigen and (b) its native conformation must be maintained for it to be an effective vaccine."}
{"id": "PMID:205370", "title": "Fine structure of crystalline inclusions in B-cells of the islets of Langerhans in the alligator.", "content": "The ultrastructure of crystalline beta granules of the islets of Langerhans in the alligator has been investigated. From optical diffraction analysis and serial sectioning, the existence of four distinct types of crystalline inclusions was established in ultrathin sections. The first type is the most frequent and is interpreted as a rhombohedron with a base, the ortho-hexagonal unit-cell edges being a equal to 18.9 nm, c equal to 23.0 nm. The second type of crystal (not observed in serial sections) is found compatible with a rhomb-dodecahedron which indexes on a cubic cell with a equal to 9.6 nm. The third type of crystal was assigned to dipyramids. Dipyramids are extremely rare, and only two diffraction patterns were obtained; their crystal system could not be determined. Prisms, which are second in abundance, represent the fourth type of crystal. Spacings as well as the symmetry differ from those of the above three crystal types and indicate a tetragonal cell with a equal to 4.2 nm, c equal to 14.2 nm. The data for the prismatic crystals are strikingly similar to those of proinsulin and may represent the first case of agreement between crystals (i) formed in vitro and studied by X-ray diffraction and (ii) those investigated in situ by electron microscopy.", "contents": "Fine structure of crystalline inclusions in B-cells of the islets of Langerhans in the alligator. The ultrastructure of crystalline beta granules of the islets of Langerhans in the alligator has been investigated. From optical diffraction analysis and serial sectioning, the existence of four distinct types of crystalline inclusions was established in ultrathin sections. The first type is the most frequent and is interpreted as a rhombohedron with a base, the ortho-hexagonal unit-cell edges being a equal to 18.9 nm, c equal to 23.0 nm. The second type of crystal (not observed in serial sections) is found compatible with a rhomb-dodecahedron which indexes on a cubic cell with a equal to 9.6 nm. The third type of crystal was assigned to dipyramids. Dipyramids are extremely rare, and only two diffraction patterns were obtained; their crystal system could not be determined. Prisms, which are second in abundance, represent the fourth type of crystal. Spacings as well as the symmetry differ from those of the above three crystal types and indicate a tetragonal cell with a equal to 4.2 nm, c equal to 14.2 nm. The data for the prismatic crystals are strikingly similar to those of proinsulin and may represent the first case of agreement between crystals (i) formed in vitro and studied by X-ray diffraction and (ii) those investigated in situ by electron microscopy."}
{"id": "PMID:205371", "title": "Lack of effect of receptor blockers on the formation of long-lasting associations between sympathetic nerves and cardiac muscle cells in vitro.", "content": "Sympathetic nerves in vitro form long-lasting, intimate, functional relationships with cardiac muscle cells, but not with fibroblasts. In the presence of an adrenergic beta-blocker and a cholinergic muscarinic blocker, long-lasting relationships still take place. It was concluded that neurotransmitter \"receptors\" are not involved in the mechanism of \"recognition\" of cardiac muscle cells by sympathetic nerves.", "contents": "Lack of effect of receptor blockers on the formation of long-lasting associations between sympathetic nerves and cardiac muscle cells in vitro. Sympathetic nerves in vitro form long-lasting, intimate, functional relationships with cardiac muscle cells, but not with fibroblasts. In the presence of an adrenergic beta-blocker and a cholinergic muscarinic blocker, long-lasting relationships still take place. It was concluded that neurotransmitter \"receptors\" are not involved in the mechanism of \"recognition\" of cardiac muscle cells by sympathetic nerves."}
{"id": "PMID:205372", "title": "Evidence for coupled synthesis of mRNA for ribosomal proteins and rRNA.", "content": "Two-dimensional gel electrophoresis revealed quantitative differences in the 35S-methionine labeled proteins synthesized in vitro in the wheat germ system containing poly A(+) mRNA of normal liver, regenerating liver or Novikoff hepatoma cells. A group of low molecular weight proteins which comigrated with proteins of 40S ribosomal subunits were synthesized in a much greater concentration with the poly A(+) mRNA from the latter two sources. This correlates with increased synthesis of ribosomal proteins in regenerating liver or tumors which is temporally coupled with the increased nucleolar synthesis of rRNA precursors.", "contents": "Evidence for coupled synthesis of mRNA for ribosomal proteins and rRNA. Two-dimensional gel electrophoresis revealed quantitative differences in the 35S-methionine labeled proteins synthesized in vitro in the wheat germ system containing poly A(+) mRNA of normal liver, regenerating liver or Novikoff hepatoma cells. A group of low molecular weight proteins which comigrated with proteins of 40S ribosomal subunits were synthesized in a much greater concentration with the poly A(+) mRNA from the latter two sources. This correlates with increased synthesis of ribosomal proteins in regenerating liver or tumors which is temporally coupled with the increased nucleolar synthesis of rRNA precursors."}
{"id": "PMID:205373", "title": "Periodate induced cross-linking of concanavalin A-reactive membrane proteins of rabbit thymocytes.", "content": "Purified plasma membranes of rabbit thymocytes are exposed to sodium periodate and galactose oxidase at conditions similar to those used to induce mitogenic transformation of lymphocytes. The membrane proteins are then fractionated by dodecyl sulfate poly-acrylamide gel electrophoresis. At concentrations of 0.005 M, Na IO4 cross-links 55,000 D and 110,000 D glycoproteins which are known to specifically bind concanavalin A. Galactose oxidase has a similar cross-linking effect, but, at the same time causes proteolytic degradation of membrane proteins. Our data indicate that oxidizing agents, like NaIO4 and galactose oxidase, can indeed cross-link receptors of the thymocyte plasma membrane as has often been proposed as a possible mechanism of their action.", "contents": "Periodate induced cross-linking of concanavalin A-reactive membrane proteins of rabbit thymocytes. Purified plasma membranes of rabbit thymocytes are exposed to sodium periodate and galactose oxidase at conditions similar to those used to induce mitogenic transformation of lymphocytes. The membrane proteins are then fractionated by dodecyl sulfate poly-acrylamide gel electrophoresis. At concentrations of 0.005 M, Na IO4 cross-links 55,000 D and 110,000 D glycoproteins which are known to specifically bind concanavalin A. Galactose oxidase has a similar cross-linking effect, but, at the same time causes proteolytic degradation of membrane proteins. Our data indicate that oxidizing agents, like NaIO4 and galactose oxidase, can indeed cross-link receptors of the thymocyte plasma membrane as has often been proposed as a possible mechanism of their action."}
{"id": "PMID:205379", "title": "The effect of experimental uremia on potassium-activated phosphatase from erythrocyte and cardiac membranes.", "content": "Unilateral nephrectomy and partial resection of the contralateral kidney in rats causes uremia that lasts for several weeks and influenced overall (Na+, K+)-ATPase activity as well as p-nitrophenyl phosphatase (p-NPPase) in the plasma membranes of erythrocytes and heart. Both enzymatic activities are inhibited to a similar extent in the uremic animals, regardless of whether the membranes were investigated one or four weeks after surgical treatment.", "contents": "The effect of experimental uremia on potassium-activated phosphatase from erythrocyte and cardiac membranes. Unilateral nephrectomy and partial resection of the contralateral kidney in rats causes uremia that lasts for several weeks and influenced overall (Na+, K+)-ATPase activity as well as p-nitrophenyl phosphatase (p-NPPase) in the plasma membranes of erythrocytes and heart. Both enzymatic activities are inhibited to a similar extent in the uremic animals, regardless of whether the membranes were investigated one or four weeks after surgical treatment."}
{"id": "PMID:205381", "title": "Detection of Fabry's disease heterozygotes by hair root analysis.", "content": "The alpha-galactosidase/beta-hexosaminidase ratio was measured for individual hair roots as a method for heterozygote detection in Fabry's disease. Hair root analysis in control individuals revealed no striking sex difference in alpha-galactosidase/beta-hexosaminidase ratio when five males and five females were compared. The values for the ratio X 100, calculating both enzyme activities in nmol of product per min per microliter of hair extract, ranged from 0.8 to 9 for controls and from less than 0.1 to 0.4 for two hemizygous males. Hair root analysis in four heterozygotes with clinical evidence of disease gave values for each individual in the control range, in the range for hemizygotes and in an intermediate range. The experience using hair root analysis for heterozygote detection in the X-linked Lesch-Nyhan syndrome suggests that this approch will be a sensitive heterozygote detection method which takes advantage of the occurrence of hairs with a deficient phenotype on the basis of Lyonization. We observed an affected male who was born to a female without clinical or biochemical evidence (examination included extensive hair root analysis) of Fabry's disease, thus documenting a likely instance of new mutation.", "contents": "Detection of Fabry's disease heterozygotes by hair root analysis. The alpha-galactosidase/beta-hexosaminidase ratio was measured for individual hair roots as a method for heterozygote detection in Fabry's disease. Hair root analysis in control individuals revealed no striking sex difference in alpha-galactosidase/beta-hexosaminidase ratio when five males and five females were compared. The values for the ratio X 100, calculating both enzyme activities in nmol of product per min per microliter of hair extract, ranged from 0.8 to 9 for controls and from less than 0.1 to 0.4 for two hemizygous males. Hair root analysis in four heterozygotes with clinical evidence of disease gave values for each individual in the control range, in the range for hemizygotes and in an intermediate range. The experience using hair root analysis for heterozygote detection in the X-linked Lesch-Nyhan syndrome suggests that this approch will be a sensitive heterozygote detection method which takes advantage of the occurrence of hairs with a deficient phenotype on the basis of Lyonization. We observed an affected male who was born to a female without clinical or biochemical evidence (examination included extensive hair root analysis) of Fabry's disease, thus documenting a likely instance of new mutation."}
{"id": "PMID:205382", "title": "Calcitriol in dialysis patients.", "content": "We conducted a 7-month randomized, single, double, single-blind comparison of calcitriol (1,25(OH)2D3) with vitamin D3 in 22 hemodialysis patients to study the effects on the biochemical abnormalities associated with osteodystrophy. Calcitriol was given for 3 mo. All patients had initial prestudy calcium values less than or equal to 9.5 mg/100 ml, and phosphate values less than or equal to 4.5 mg/100 ml. Data were analyzed using the Normalized Trend Index (NTI). Calcitriol induced a rise in calcium (8.7 to 10.25 mg/100 ml) (p less than 0.001) and a fall in alkaline phosphatase (p less than 0.005), while D3 had no appreciable effect. The mean dose of calcitriol during treatment was 0.579 microgram/day while that for D3 was 706 IU/day. The effect on serum phosphate concentration was variable. Hypercalcemia as high as 13.2 mg/100 ml occurred in 2 of 13 patients on 1,25(OH)2D3, but in every instance promptly returned to normal with dose reduction. No other adverse effects were noted with therapy. We conclude that calcitriol reverses the biochemical abnormalities of osteodystrophy. Since its effects are rapidly reversed with discontinuation, the drug is probably safe as well as effective.", "contents": "Calcitriol in dialysis patients. We conducted a 7-month randomized, single, double, single-blind comparison of calcitriol (1,25(OH)2D3) with vitamin D3 in 22 hemodialysis patients to study the effects on the biochemical abnormalities associated with osteodystrophy. Calcitriol was given for 3 mo. All patients had initial prestudy calcium values less than or equal to 9.5 mg/100 ml, and phosphate values less than or equal to 4.5 mg/100 ml. Data were analyzed using the Normalized Trend Index (NTI). Calcitriol induced a rise in calcium (8.7 to 10.25 mg/100 ml) (p less than 0.001) and a fall in alkaline phosphatase (p less than 0.005), while D3 had no appreciable effect. The mean dose of calcitriol during treatment was 0.579 microgram/day while that for D3 was 706 IU/day. The effect on serum phosphate concentration was variable. Hypercalcemia as high as 13.2 mg/100 ml occurred in 2 of 13 patients on 1,25(OH)2D3, but in every instance promptly returned to normal with dose reduction. No other adverse effects were noted with therapy. We conclude that calcitriol reverses the biochemical abnormalities of osteodystrophy. Since its effects are rapidly reversed with discontinuation, the drug is probably safe as well as effective."}
{"id": "PMID:205383", "title": "Radiology of needle biopsy of pulmonary lesions.", "content": "A technique for percutaneous aspiration needle biopsy is described and discussed. It is concluded that it forms a simple and easy way of obtaining histological material and it can be carried out in most radiological departments.", "contents": "Radiology of needle biopsy of pulmonary lesions. A technique for percutaneous aspiration needle biopsy is described and discussed. It is concluded that it forms a simple and easy way of obtaining histological material and it can be carried out in most radiological departments."}
{"id": "PMID:205385", "title": "Lecithin--cholesterol acyltransferase and the lipoprotein abnormalities of obstructive jaundice.", "content": "1. We have studied the plasma lipoprotein abnormalities in obstructive jaundice to test the hypothesis that the abnormalities would correlate with plasma lecithin--cholesterol acyltransferase activity. 2. Very-low-density lipoproteins (VLDL) were normal in composition and had a normal pre-beta electrophoretic mobility when lecithin--cholesterol acyltransferase activity was high. When it was low VLDL had abnormal composition and ran in the beta position. 3. With high lecithin--cholesterol acyltransferase activity, low-density lipoprotein (LDL) was normal and cholestatic LDL (LP-X) was not found. With low lecithin--cholesterol acyltransferase activity up to three LDL fractions were found: (i) large triglyceride-rich particles, (ii) LP-X and (iii) a triglyceride-rich cholesteryl ester-poor particle of normal dimensions. 4. High-density lipoprotein (HDL) concentrations correlated with lecithin--cholesterol acyltransferase activity and HDL were normal in composition and electron-microscopic appearance when the activity was high. When lecithin--cholesterol acyltransferase activity was low HDL was abnormal in composition and 'stacked discs' were seen on electron microscopy as well as normal spherical particles. 5. These results suggest that low lecithin-cholesterol acyltransferase activity may cause at least some of the lipoprotein changes of obstructive jaundice.", "contents": "Lecithin--cholesterol acyltransferase and the lipoprotein abnormalities of obstructive jaundice. 1. We have studied the plasma lipoprotein abnormalities in obstructive jaundice to test the hypothesis that the abnormalities would correlate with plasma lecithin--cholesterol acyltransferase activity. 2. Very-low-density lipoproteins (VLDL) were normal in composition and had a normal pre-beta electrophoretic mobility when lecithin--cholesterol acyltransferase activity was high. When it was low VLDL had abnormal composition and ran in the beta position. 3. With high lecithin--cholesterol acyltransferase activity, low-density lipoprotein (LDL) was normal and cholestatic LDL (LP-X) was not found. With low lecithin--cholesterol acyltransferase activity up to three LDL fractions were found: (i) large triglyceride-rich particles, (ii) LP-X and (iii) a triglyceride-rich cholesteryl ester-poor particle of normal dimensions. 4. High-density lipoprotein (HDL) concentrations correlated with lecithin--cholesterol acyltransferase activity and HDL were normal in composition and electron-microscopic appearance when the activity was high. When lecithin--cholesterol acyltransferase activity was low HDL was abnormal in composition and 'stacked discs' were seen on electron microscopy as well as normal spherical particles. 5. These results suggest that low lecithin-cholesterol acyltransferase activity may cause at least some of the lipoprotein changes of obstructive jaundice."}
{"id": "PMID:205386", "title": "Effect of antitonin on blood pressure in the one-kidney hypertensive rat.", "content": "1. The tonin concentration of saliva and submaxillary glands was studied in one-clip hypertensive rats with or without the contralateral kidney. 2. Salivary tonin concentration was elevated in one-kidney hypertensive rats, but not in one-kidney normotensive or two-kidney, one-clip hypertensive rats. In contrast, an elevated submaxillary gland tonin concentration was found only in uninephrectomized animals, whether normotensive or hypertensive. 3. A single intravenous administration of rabbit tonin antiserum into one-kidney 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. 4. These findings suggest a connection between the physiology of the kidney and of the submaxillary gland in the rat, and indicate that tonin may play a significant role in maintaining high blood pressure in one-kidney hypertensive aniamls.", "contents": "Effect of antitonin on blood pressure in the one-kidney hypertensive rat. 1. The tonin concentration of saliva and submaxillary glands was studied in one-clip hypertensive rats with or without the contralateral kidney. 2. Salivary tonin concentration was elevated in one-kidney hypertensive rats, but not in one-kidney normotensive or two-kidney, one-clip hypertensive rats. In contrast, an elevated submaxillary gland tonin concentration was found only in uninephrectomized animals, whether normotensive or hypertensive. 3. A single intravenous administration of rabbit tonin antiserum into one-kidney 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. 4. These findings suggest a connection between the physiology of the kidney and of the submaxillary gland in the rat, and indicate that tonin may play a significant role in maintaining high blood pressure in one-kidney hypertensive aniamls."}
{"id": "PMID:205388", "title": "The importance of adrenocortical steroids in the pathogenesis of ketosis in diabetic guinea pigs (Caviae porcellus)", "content": "The roles of adrenocortical steroids in the pathogenesis of diabetic ketosis were investigated in guinea pigs. Groups of normal and Streptozotocin-induced diabetic animals were either given saline as a control, methylprednisilone as an exogenous steroid, or adrenocorticotrophin to stimulate endogenous steroid production. Plasma and urine ketone determinations were made daily for six days at which time animals were necropsied. The qualitative procedure used failed to detect ketonemia, and ketonuria was only found in diabetic guinea pigs treated with steroids. The results support the hypothesis that the absence of ketosis in spontaneously diabetic guinea pigs may be the result of a relative glucocorticoid insufficiency secondary to fatty degeneration of the adrenal glands, a common lesion in spontaneously diabetic guinea pigs.", "contents": "The importance of adrenocortical steroids in the pathogenesis of ketosis in diabetic guinea pigs (Caviae porcellus). The roles of adrenocortical steroids in the pathogenesis of diabetic ketosis were investigated in guinea pigs. Groups of normal and Streptozotocin-induced diabetic animals were either given saline as a control, methylprednisilone as an exogenous steroid, or adrenocorticotrophin to stimulate endogenous steroid production. Plasma and urine ketone determinations were made daily for six days at which time animals were necropsied. The qualitative procedure used failed to detect ketonemia, and ketonuria was only found in diabetic guinea pigs treated with steroids. The results support the hypothesis that the absence of ketosis in spontaneously diabetic guinea pigs may be the result of a relative glucocorticoid insufficiency secondary to fatty degeneration of the adrenal glands, a common lesion in spontaneously diabetic guinea pigs."}
{"id": "PMID:205389", "title": "Quantitative ESR-studies of decay-produced radicals in 5-iododeoxyuridine labeled with 125I, 131I or tritium: role of the Auger effect.", "content": "In view of the enhanced biological damage caused by the \"Auger nuclide\" iodine-125, we have carried out quantitative ESR-studies of the radical formation in polycrystalline 5-iododoeoxyuridine (IUdR) resulting from the following internal or external radiation sources: (1) Decay of 3H, 125I or 131I in labeled IUdR; (2) Lanthanum K-photons corresponding to the K-edge of iodine; (3) 60Co gamma-rays. The results clearly indicate that inner shell ionization with its accompanying Auger effect as caused by the lanthanum K X-ray produces about 30% more free radicals per unit dose absorbed than 60Co gamma-rays, when considering the long-lived secondary radicals. Similarly, the concentration of free radicals is by about 30% higher in 125I- than in 131I-labeled IUdR at comparable doses. In the case of 3H-labeled IUdR the dose curve is almost identical with that observed for 125I-labeled IUdR. The results are discussed in terms of a localized radiation damage from low energy electrons.", "contents": "Quantitative ESR-studies of decay-produced radicals in 5-iododeoxyuridine labeled with 125I, 131I or tritium: role of the Auger effect. In view of the enhanced biological damage caused by the \"Auger nuclide\" iodine-125, we have carried out quantitative ESR-studies of the radical formation in polycrystalline 5-iododoeoxyuridine (IUdR) resulting from the following internal or external radiation sources: (1) Decay of 3H, 125I or 131I in labeled IUdR; (2) Lanthanum K-photons corresponding to the K-edge of iodine; (3) 60Co gamma-rays. The results clearly indicate that inner shell ionization with its accompanying Auger effect as caused by the lanthanum K X-ray produces about 30% more free radicals per unit dose absorbed than 60Co gamma-rays, when considering the long-lived secondary radicals. Similarly, the concentration of free radicals is by about 30% higher in 125I- than in 131I-labeled IUdR at comparable doses. In the case of 3H-labeled IUdR the dose curve is almost identical with that observed for 125I-labeled IUdR. The results are discussed in terms of a localized radiation damage from low energy electrons."}
{"id": "PMID:205390", "title": "The swollen limb: cutaneous clues to diagnosis and treatment.", "content": "We have reviewed a wide spectrum of disorders producing a swollen limb, some common, others uncommon. Cutaneous signs are often seen in association with these conditions and careful attention to them by the dermatologist may be helpful in determining an accurate diagnosis and appropriate therapy.", "contents": "The swollen limb: cutaneous clues to diagnosis and treatment. We have reviewed a wide spectrum of disorders producing a swollen limb, some common, others uncommon. Cutaneous signs are often seen in association with these conditions and careful attention to them by the dermatologist may be helpful in determining an accurate diagnosis and appropriate therapy."}
{"id": "PMID:205391", "title": "Fine structure of wall bodies in large cells of an Anabaena species.", "content": "A new type of inclusion in blue-green algae termed a wall body is described. These are elongate bodies of medium electron density, from 6 to 70 nm in thickness and at least 0.2 micrometer in depth found in large cells of Anabaena sp. B387. The bodies are up to 12 micrometer long, extending the complete length of the cell in some cases. Some of the bodies are bifurcated and the ends appeared to come in contact with the plasma membrane. The wall bodies lie at various angles in the cells. Up to six have been observed in a single thin section of a cell. The large cells are found in greater numbers in cultures grown in a medium solidified with agar. Comparison of the bodies to the mucopolymer layer (layer 2) of the cell wall is made.", "contents": "Fine structure of wall bodies in large cells of an Anabaena species. A new type of inclusion in blue-green algae termed a wall body is described. These are elongate bodies of medium electron density, from 6 to 70 nm in thickness and at least 0.2 micrometer in depth found in large cells of Anabaena sp. B387. The bodies are up to 12 micrometer long, extending the complete length of the cell in some cases. Some of the bodies are bifurcated and the ends appeared to come in contact with the plasma membrane. The wall bodies lie at various angles in the cells. Up to six have been observed in a single thin section of a cell. The large cells are found in greater numbers in cultures grown in a medium solidified with agar. Comparison of the bodies to the mucopolymer layer (layer 2) of the cell wall is made."}
{"id": "PMID:205387", "title": "Yunnan Bai Yao-induced platelet release in suspensions of washed platelets.", "content": "The effects of Yunnan Bai Yao on platelets was investigated in the absence of plasma co-factors. Platelets were washed with Tyrode's solution and incubated with this herbal drug at 37 degrees C. It was found that this drug can, to a lesser extent, also induce the release of platelet constituents in the absence of the plasma co-factors. The possible action of this drug is also discussed.", "contents": "Yunnan Bai Yao-induced platelet release in suspensions of washed platelets. The effects of Yunnan Bai Yao on platelets was investigated in the absence of plasma co-factors. Platelets were washed with Tyrode's solution and incubated with this herbal drug at 37 degrees C. It was found that this drug can, to a lesser extent, also induce the release of platelet constituents in the absence of the plasma co-factors. The possible action of this drug is also discussed."}
{"id": "PMID:205394", "title": "Endocrine and pharmacological factors which influence the onset of labour in rhesus monkeys.", "content": "Indomethacin administration in late pregnancy prolonged gestation in caged rhesus monkeys and inhibited premature labour and postponed delivery in chronically catheterized monkey fetuses. Chronic indomethacin treatment was associated with a reduction in the urinary excretion of a prostaglandin metabolite, a potent inhibitory effect on myometrial cyclic AMP phosphodiesterase, and severe oligohydramnios in pre-term and post-term fetuses. Experimental anencephaly (functional hypophysectomy) of the rhesus fetus results in lowered concentrations of maternal oestradiol and loss of the precise control of gestational length, with 40% of fetuses delivering beyond term. Corticotropin (ACTH) infused into the fetus results in raised concentrations of fetal and maternal cortisol, progesterone and oestrogens. Progesterone concentrations in peripheral blood apparently have little bearing on uterine quiescence in the rhesus monkey, since the concentrations of progesterone in maternal and fetal blood vary directly with uterine activity. The results of chronic infusion of corticotropin in the fetal monkey support the theory that in the monkey parturition is mediated by increased oestrogen production by the fetoplacental unit and by a rise in the concentrations of oestrone and prostaglandin in the amniotic fluid.", "contents": "Endocrine and pharmacological factors which influence the onset of labour in rhesus monkeys. Indomethacin administration in late pregnancy prolonged gestation in caged rhesus monkeys and inhibited premature labour and postponed delivery in chronically catheterized monkey fetuses. Chronic indomethacin treatment was associated with a reduction in the urinary excretion of a prostaglandin metabolite, a potent inhibitory effect on myometrial cyclic AMP phosphodiesterase, and severe oligohydramnios in pre-term and post-term fetuses. Experimental anencephaly (functional hypophysectomy) of the rhesus fetus results in lowered concentrations of maternal oestradiol and loss of the precise control of gestational length, with 40% of fetuses delivering beyond term. Corticotropin (ACTH) infused into the fetus results in raised concentrations of fetal and maternal cortisol, progesterone and oestrogens. Progesterone concentrations in peripheral blood apparently have little bearing on uterine quiescence in the rhesus monkey, since the concentrations of progesterone in maternal and fetal blood vary directly with uterine activity. The results of chronic infusion of corticotropin in the fetal monkey support the theory that in the monkey parturition is mediated by increased oestrogen production by the fetoplacental unit and by a rise in the concentrations of oestrone and prostaglandin in the amniotic fluid."}
{"id": "PMID:205396", "title": "The fetal hypothalamus and pituitary in the initiation of labour.", "content": "Evidence is presented for a number of events in the fetal hypothalamic-pituitary axis which may play a key role in the onset of labour: (1) In the sheep fetus a progressive rise in the fetal circulating concentrations of corticotropin in the days preceding delivery; (2) In the human fetus a switch from the production of corticotropin-like fragments (melanotropin and corticotropin-like intermediate lobe peptide) to authentic corticotropin in the last weeks of gestation; there is evidence also for a placental origin of corticotropin; (3) In the human fetus, a release of oxytocin and vasopressin associated with the process of spontaneous labour.", "contents": "The fetal hypothalamus and pituitary in the initiation of labour. Evidence is presented for a number of events in the fetal hypothalamic-pituitary axis which may play a key role in the onset of labour: (1) In the sheep fetus a progressive rise in the fetal circulating concentrations of corticotropin in the days preceding delivery; (2) In the human fetus a switch from the production of corticotropin-like fragments (melanotropin and corticotropin-like intermediate lobe peptide) to authentic corticotropin in the last weeks of gestation; there is evidence also for a placental origin of corticotropin; (3) In the human fetus, a release of oxytocin and vasopressin associated with the process of spontaneous labour."}
{"id": "PMID:205397", "title": "Fetal cortisol and the initiation of labour in the human.", "content": "The role of the fetal adrenal activity in the initiation of parturition in the human has been investigated. Women were studied in the last trimester of pregnancy during treatment with betamethasone for prevention of the idiopathic respiratory distress syndrome. Although betamethasone caused a considerable drop in the cortisol concentrations of fetal plasma and amniotic fluid, the time to spontaneous delivery in this group was similar to that in matched controls. Moreover, cortisol in fetal scalp blood at the onset of parturition in untreated women did not differ between those with spontaneous and those with induced labour. Evidence is given that increase of circulating cortisol in the fetus during the course of parturition predominantly reflects a rise in maternal cortisol under the influence of labour. The strain of labour seems to partly override the betamethasone-induced inhibition of maternal cortisol release. The possible ability of the fetal adrenals to respond to stimuli is illustrated by comparison of cortisol concentrations in cord plasma after various forms of complicated deliveries.", "contents": "Fetal cortisol and the initiation of labour in the human. The role of the fetal adrenal activity in the initiation of parturition in the human has been investigated. Women were studied in the last trimester of pregnancy during treatment with betamethasone for prevention of the idiopathic respiratory distress syndrome. Although betamethasone caused a considerable drop in the cortisol concentrations of fetal plasma and amniotic fluid, the time to spontaneous delivery in this group was similar to that in matched controls. Moreover, cortisol in fetal scalp blood at the onset of parturition in untreated women did not differ between those with spontaneous and those with induced labour. Evidence is given that increase of circulating cortisol in the fetus during the course of parturition predominantly reflects a rise in maternal cortisol under the influence of labour. The strain of labour seems to partly override the betamethasone-induced inhibition of maternal cortisol release. The possible ability of the fetal adrenals to respond to stimuli is illustrated by comparison of cortisol concentrations in cord plasma after various forms of complicated deliveries."}
{"id": "PMID:205398", "title": "Parturition in the sheep.", "content": "Parturition in sheep is initiated by a sharp rise in the rate of secretion of cortisol by the fetal adrenal. Increased secretion is due partly to enhanced responsiveness to corticotropin (ACTH) and partly to increased fetal concentrations of corticotropin. Cortisol acts on placental enzymes active in the biosynthesis of oestrogens from progesterone. Thus placental secretion of oestrogen increases and that of progesterone decreases. This change in the ratio of oestrogen: progesterone, particularly the rise in oestrogen, stimulates release of prostaglandin F2alpha (PGF2alpha) from the maternal placenta and to a lesser extent from the myometrium. PGF2alpha enhances the myometrial response to oxytocin and, after a latent period, stimulates contractions. The onset of parturition is normally associated with softening of the cervix, the mechanism of which is uncertain. Uterine contractions in the presence of a distensible cervix lead to parturition.", "contents": "Parturition in the sheep. Parturition in sheep is initiated by a sharp rise in the rate of secretion of cortisol by the fetal adrenal. Increased secretion is due partly to enhanced responsiveness to corticotropin (ACTH) and partly to increased fetal concentrations of corticotropin. Cortisol acts on placental enzymes active in the biosynthesis of oestrogens from progesterone. Thus placental secretion of oestrogen increases and that of progesterone decreases. This change in the ratio of oestrogen: progesterone, particularly the rise in oestrogen, stimulates release of prostaglandin F2alpha (PGF2alpha) from the maternal placenta and to a lesser extent from the myometrium. PGF2alpha enhances the myometrial response to oxytocin and, after a latent period, stimulates contractions. The onset of parturition is normally associated with softening of the cervix, the mechanism of which is uncertain. Uterine contractions in the presence of a distensible cervix lead to parturition."}
{"id": "PMID:205401", "title": "[Ossification of the auricle in partial pituitary failure with selective ACTH and STH deficiency (author's transl)].", "content": "An acquired partial pituitary insufficiency of unknown origin with selective ACTH and STH deficiency was demonstrated in a 44-year-old patient. The clinical course over many years corresponds to subclinical Addison's disease with occasional acute crises. Ossification of both auricular cartilages and anhidrosis were outstanding signs. There is possibly a connection between the glucocorticoid deficiency over many years with normal mineralocorticoids and the auricular cartilage ossification.", "contents": "[Ossification of the auricle in partial pituitary failure with selective ACTH and STH deficiency (author's transl)]. An acquired partial pituitary insufficiency of unknown origin with selective ACTH and STH deficiency was demonstrated in a 44-year-old patient. The clinical course over many years corresponds to subclinical Addison's disease with occasional acute crises. Ossification of both auricular cartilages and anhidrosis were outstanding signs. There is possibly a connection between the glucocorticoid deficiency over many years with normal mineralocorticoids and the auricular cartilage ossification."}
{"id": "PMID:205403", "title": "[Photosensitivity in children with malign tumors (author's transl)].", "content": "Photosensitivity (photoconvulsive reaction = PCR) has to be regarded as a genetically determined EEG-symptom, which is seen with markedly age dependent in up to 15% of healthy individuals. Correlations with epileptic and nonepileptic diseases (migraine, anorexia nervosa, psychovegetativ instability) are known. 157 children with malign tumors (Tab 1) were investigated. Children with Wilms' tumors showed significant more PCR than all other children with malign tumors (Tab. 2, 3). That finding may corroborate the hypothesis, that Wilms' tumor may be the most important clinical symptom of syndroms with congenital malformations (aniridy, hamartom, hemihypertrophy).", "contents": "[Photosensitivity in children with malign tumors (author's transl)]. Photosensitivity (photoconvulsive reaction = PCR) has to be regarded as a genetically determined EEG-symptom, which is seen with markedly age dependent in up to 15% of healthy individuals. Correlations with epileptic and nonepileptic diseases (migraine, anorexia nervosa, psychovegetativ instability) are known. 157 children with malign tumors (Tab 1) were investigated. Children with Wilms' tumors showed significant more PCR than all other children with malign tumors (Tab. 2, 3). That finding may corroborate the hypothesis, that Wilms' tumor may be the most important clinical symptom of syndroms with congenital malformations (aniridy, hamartom, hemihypertrophy)."}
{"id": "PMID:205404", "title": "Release of cyclic AMP from the chicken thyroid stimulated with TSH in vitro.", "content": "The thyroid lobes excised from one-day-old or 13-day-old chickens were incubated with or without TSH, and cAMP in the medium was determined. TSH induced the release of cAMP from thyroid lobes, resulting in the increase of cAMP concentration in the incubating medium. The release of cAMP into the incubating media in the presence of TSH from the thyroids of the chickens which were pretreated with TSH neonatally was more marked as compared to that from the thyroids of the control chickens. The light and electron microscopic examination of the thyroid lobes incubated with TSH showed that the morphological changes such as colloid droplets formation and enlargement of endoplasmic reticulum were induced.", "contents": "Release of cyclic AMP from the chicken thyroid stimulated with TSH in vitro. The thyroid lobes excised from one-day-old or 13-day-old chickens were incubated with or without TSH, and cAMP in the medium was determined. TSH induced the release of cAMP from thyroid lobes, resulting in the increase of cAMP concentration in the incubating medium. The release of cAMP into the incubating media in the presence of TSH from the thyroids of the chickens which were pretreated with TSH neonatally was more marked as compared to that from the thyroids of the control chickens. The light and electron microscopic examination of the thyroid lobes incubated with TSH showed that the morphological changes such as colloid droplets formation and enlargement of endoplasmic reticulum were induced."}
{"id": "PMID:205405", "title": "Studies on reduction of lipolysis in adipose tissue on freezing and thawing.", "content": "Adrenaline-induced lipolysis in fat cells was remarkably reduced when the cells were preincubated in a dry ice-aceton bath, but their adenylcyclase and lipase activities were not reduced. In the reconstructed lipid micelles which consisted of lipase-depleted lipid micelles and lipase-containing adipose tissue extract, adrenaline, theophylline and DBcAMP-induced lipolysis was not found when lipase-depleted lipid micelles were preincubated in a dry ice-aceton bath but was found when lipase was preincubated.", "contents": "Studies on reduction of lipolysis in adipose tissue on freezing and thawing. Adrenaline-induced lipolysis in fat cells was remarkably reduced when the cells were preincubated in a dry ice-aceton bath, but their adenylcyclase and lipase activities were not reduced. In the reconstructed lipid micelles which consisted of lipase-depleted lipid micelles and lipase-containing adipose tissue extract, adrenaline, theophylline and DBcAMP-induced lipolysis was not found when lipase-depleted lipid micelles were preincubated in a dry ice-aceton bath but was found when lipase was preincubated."}
{"id": "PMID:205406", "title": "[Morphological classification of pituitary adenomas and its value for clinical diagnosis].", "content": "Pituitary adenomas should be classified not only by their tinctorial affinities but also by their degree of differentiation. Then useful correlation to the clinical data can be obtained; On this principle our own collection of 299 tumors was classified in undifferentiated acidophilic, highly differentiated acidophilic GH cell-, highly differentiated acidophilic prolactin cell-adenomas, in undifferentiated mucoid cell-, highly differentiated mucoid ACTH cell-, highly differentiated mucoid TSH cell-adenomas, in chromophobic adenomas of small cell type and of large cell type, and in oncocytic adenomas. 95% of the cases with acromegaly based on undifferentiated acidophilic or highly differentiated GH cell adenomas. All patients with hypothalamic-hypophyseal Cushing's syndrome or Nelson's syndrome had undifferentiated mucoid cell adenomas or highly differentiated ACTH cell adenomas. In cases with hyperprolactinemia prolactin cell adenomas or chromophobic adenomas of large cell type with ultrastructurally demonstrated very highly developed rough endoplasmic reticulum or endocrinologically inactive chromophobic adenomas of small cell type were found. In the latter cases the prolactin is probably produced not by the tumor but by the surrounding tumor-free pituitary tissue.", "contents": "[Morphological classification of pituitary adenomas and its value for clinical diagnosis]. Pituitary adenomas should be classified not only by their tinctorial affinities but also by their degree of differentiation. Then useful correlation to the clinical data can be obtained; On this principle our own collection of 299 tumors was classified in undifferentiated acidophilic, highly differentiated acidophilic GH cell-, highly differentiated acidophilic prolactin cell-adenomas, in undifferentiated mucoid cell-, highly differentiated mucoid ACTH cell-, highly differentiated mucoid TSH cell-adenomas, in chromophobic adenomas of small cell type and of large cell type, and in oncocytic adenomas. 95% of the cases with acromegaly based on undifferentiated acidophilic or highly differentiated GH cell adenomas. All patients with hypothalamic-hypophyseal Cushing's syndrome or Nelson's syndrome had undifferentiated mucoid cell adenomas or highly differentiated ACTH cell adenomas. In cases with hyperprolactinemia prolactin cell adenomas or chromophobic adenomas of large cell type with ultrastructurally demonstrated very highly developed rough endoplasmic reticulum or endocrinologically inactive chromophobic adenomas of small cell type were found. In the latter cases the prolactin is probably produced not by the tumor but by the surrounding tumor-free pituitary tissue."}
{"id": "PMID:205407", "title": "Human erythrocyte proteins associated with adenosine 3',5'-cyclic monophosphate action.", "content": "Two adenosine 3',5'-cyclic monophosphate (cyclic-AMP)-binding protein factors (molecular weight 230,000) have been partially purified from human erythrocytes. One of these proteins seems to be different from the cyclic-AMP-binding component of the cyclic-AMP-dependent protein kinases. These protein factors are also capable of binding adenosine. We present data also on two forms of cyclic-AMP-dependent protein kinases (ATP: protein phosphotransferase, EC 2.7.1.37) partially purified from the cytosol of normal human erythrocytes. Kinase I has been classified as type I enzyme on the basis of its activation when preincubated with protamine, histone or NaCl. The substrate specificities of the two kinases and many of their kinetic parameters are rather similar. Their subunit structure is reminiscent of that of kinases obtained from other sources. The catalytic subunit of both enzymes reversibly cross-react with the regulatory subunit of kinase I from the rabbit red blood cell.", "contents": "Human erythrocyte proteins associated with adenosine 3',5'-cyclic monophosphate action. Two adenosine 3',5'-cyclic monophosphate (cyclic-AMP)-binding protein factors (molecular weight 230,000) have been partially purified from human erythrocytes. One of these proteins seems to be different from the cyclic-AMP-binding component of the cyclic-AMP-dependent protein kinases. These protein factors are also capable of binding adenosine. We present data also on two forms of cyclic-AMP-dependent protein kinases (ATP: protein phosphotransferase, EC 2.7.1.37) partially purified from the cytosol of normal human erythrocytes. Kinase I has been classified as type I enzyme on the basis of its activation when preincubated with protamine, histone or NaCl. The substrate specificities of the two kinases and many of their kinetic parameters are rather similar. Their subunit structure is reminiscent of that of kinases obtained from other sources. The catalytic subunit of both enzymes reversibly cross-react with the regulatory subunit of kinase I from the rabbit red blood cell."}
{"id": "PMID:205408", "title": "D-penicillamine and enzymatic activities.", "content": "The influence of incubation with D-penicillamine on pure enzyme preparations and on enzymatic activities of serum and skin homogenates was investigated. Three of the nine enzymatic activities studied underwent significant changes. Such effects of D-penicillamine must be taken into consideration if therapeutic or unwanted actions of this drug are to be fully understood; they are elicited by concentrations reached under conditions used for human therapy.", "contents": "D-penicillamine and enzymatic activities. The influence of incubation with D-penicillamine on pure enzyme preparations and on enzymatic activities of serum and skin homogenates was investigated. Three of the nine enzymatic activities studied underwent significant changes. Such effects of D-penicillamine must be taken into consideration if therapeutic or unwanted actions of this drug are to be fully understood; they are elicited by concentrations reached under conditions used for human therapy."}
{"id": "PMID:205412", "title": "The influence of exogenous and of membrane-bound phosphatidate concentration on the activity of CTP: phosphatidate cytidylyltransferase and phosphatidate phosphohydrolase.", "content": "Rat liver microsomes were treated with phospholipase D to obtain microsomal membranes with varying amounts of membrane-bound phosphatidate. This treatment did not impair the activity of two microsomal-bound enzymes acting with phosphatidate as substrate, i.e. CTP: phosphatidate cytidylyltransferase and phosphatidate phosphohydrolase. The dependency of the activity of these enzymes on the concentration of membrane-bound phosphatidate was determined. Both enzymes showed a linear increase in activity with membrane-bound phosphatidate concentrations up to at least 100 nmol phosphatidate/mg microsomal protein. These results indicate that both enzymes have a large reserve capacity and suggest that the enzymes are operating intracellularly, i.e. at phosphatidate concentrations of 5-10 nmol/mg endoplasmic reticulum protein, far below their maximal capacity. The ratio of phosphatidate conversion into CDP-diglyceride and 1,2-diglyceride seems to be constant for a large range of membrane-bound phosphatidate concentrations. The membrane-bound enzymes cannot utilize phosphatidate substrate present in heat-denatured membranes, but are active on phosphatidate incorporated into membranes of phospholipid vesicles.", "contents": "The influence of exogenous and of membrane-bound phosphatidate concentration on the activity of CTP: phosphatidate cytidylyltransferase and phosphatidate phosphohydrolase. Rat liver microsomes were treated with phospholipase D to obtain microsomal membranes with varying amounts of membrane-bound phosphatidate. This treatment did not impair the activity of two microsomal-bound enzymes acting with phosphatidate as substrate, i.e. CTP: phosphatidate cytidylyltransferase and phosphatidate phosphohydrolase. The dependency of the activity of these enzymes on the concentration of membrane-bound phosphatidate was determined. Both enzymes showed a linear increase in activity with membrane-bound phosphatidate concentrations up to at least 100 nmol phosphatidate/mg microsomal protein. These results indicate that both enzymes have a large reserve capacity and suggest that the enzymes are operating intracellularly, i.e. at phosphatidate concentrations of 5-10 nmol/mg endoplasmic reticulum protein, far below their maximal capacity. The ratio of phosphatidate conversion into CDP-diglyceride and 1,2-diglyceride seems to be constant for a large range of membrane-bound phosphatidate concentrations. The membrane-bound enzymes cannot utilize phosphatidate substrate present in heat-denatured membranes, but are active on phosphatidate incorporated into membranes of phospholipid vesicles."}
{"id": "PMID:205413", "title": "Investigation on the kinetic mechanism of octopine dehydrogenase. A regulatory behavior.", "content": "The kinetic scheme of octopine dehydrogenase of Pecten maximus L., a monomeric enzyme obeying a bi-ter sequential mechanism, was completed, essentially in the forward reaction, by steady-state studies over a wide range of substrate concentration at pH 7.0. Deviation from the Michaelis-Menten behavior with respect to NAD+ and other significant kinetic data led us to ascribe for octopine dehydrogenase mechanism the mnemonical enzyme concept. In addition, another regulatory behavior can be envisaged involving the formation of two dead-end complexes enzyme.NADH.D-octopine and enzyme.NAD+.pyruvate.L-arginine.", "contents": "Investigation on the kinetic mechanism of octopine dehydrogenase. A regulatory behavior. The kinetic scheme of octopine dehydrogenase of Pecten maximus L., a monomeric enzyme obeying a bi-ter sequential mechanism, was completed, essentially in the forward reaction, by steady-state studies over a wide range of substrate concentration at pH 7.0. Deviation from the Michaelis-Menten behavior with respect to NAD+ and other significant kinetic data led us to ascribe for octopine dehydrogenase mechanism the mnemonical enzyme concept. In addition, another regulatory behavior can be envisaged involving the formation of two dead-end complexes enzyme.NADH.D-octopine and enzyme.NAD+.pyruvate.L-arginine."}
{"id": "PMID:205414", "title": "A novel type of endotoxin structure present in Bordetella pertussis. Isolation of two different polysaccharides bound to lipid A.", "content": "The endotoxin of Bordetella pertussis was cleaved by mild acidic hydrolysis to yield a polysaccharide (polysaccharide I, 15%), a glycolipid (63%) and lipid X (2%). Further treatment of the glycolipid with stronger acid released a second polysaccharide (polysaccharide II, 9%) and material similar to lipid A present in enterobacterial endotoxins. Both polysaccharides possess a single molecule of 3-deoxy-2-octulosonic acid as the reducing, terminal sugar. In polysaccharide II the octulosonic acid is phosphorylated in position 5 and presumably substituted in position 4; in polysaccharide I the octulosonic acid is not phosphorylated, but is substituted in position 5. Following treatment of the endotoxin with strong base, a fragment was isolated that contained bound, non-phosphorylated 3-deoxy-2-octulosonic acid, glucosamine phosphate and fatty acids. This indicated that polysaccharide I, like polysaccharide II, was bound to the lipid region of the endotoxin. The endotoxin structure thus defined is different from that proposed for the lipopolysaccharides of enterobacteria.", "contents": "A novel type of endotoxin structure present in Bordetella pertussis. Isolation of two different polysaccharides bound to lipid A. The endotoxin of Bordetella pertussis was cleaved by mild acidic hydrolysis to yield a polysaccharide (polysaccharide I, 15%), a glycolipid (63%) and lipid X (2%). Further treatment of the glycolipid with stronger acid released a second polysaccharide (polysaccharide II, 9%) and material similar to lipid A present in enterobacterial endotoxins. Both polysaccharides possess a single molecule of 3-deoxy-2-octulosonic acid as the reducing, terminal sugar. In polysaccharide II the octulosonic acid is phosphorylated in position 5 and presumably substituted in position 4; in polysaccharide I the octulosonic acid is not phosphorylated, but is substituted in position 5. Following treatment of the endotoxin with strong base, a fragment was isolated that contained bound, non-phosphorylated 3-deoxy-2-octulosonic acid, glucosamine phosphate and fatty acids. This indicated that polysaccharide I, like polysaccharide II, was bound to the lipid region of the endotoxin. The endotoxin structure thus defined is different from that proposed for the lipopolysaccharides of enterobacteria."}
{"id": "PMID:205415", "title": "Kinetic evidence for interaction between aldolase and D-glyceraldehyde-3-phosphate dehydrogenase.", "content": "The possibility of interaction between purified rabbit muscle aldolase and D-glyceraldehyde-3-phosphate dehydrogenase was studied by rapid kinetic methods, by analyzing the kinetics of the consecutive reaction catalyzed by the coupled enzyme system. The Km of the intermediary product, glyceraldehyde 3-phosphate, produced by aldolase was determined in the coupled reaction for glyceraldehyde-3-phosphate dehydrogenase. Its value corresponds to that of the aldehyde (active) form of glyceraldehyde 3-phosphate, although in the given conditions the aldehyde leads to diol interconversion is faster than the enzymic reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase. We suggest that above a certain concentration of the enzymes the glyceraldehyde 3-phosphate produced by aldolase gets direct access to glyceraldehyde-3-phosphate dehydrogenase without participating in the aldehyde leads to diol interconversion which otherwise would occur if the substrate were to mix with the bulk medium.", "contents": "Kinetic evidence for interaction between aldolase and D-glyceraldehyde-3-phosphate dehydrogenase. The possibility of interaction between purified rabbit muscle aldolase and D-glyceraldehyde-3-phosphate dehydrogenase was studied by rapid kinetic methods, by analyzing the kinetics of the consecutive reaction catalyzed by the coupled enzyme system. The Km of the intermediary product, glyceraldehyde 3-phosphate, produced by aldolase was determined in the coupled reaction for glyceraldehyde-3-phosphate dehydrogenase. Its value corresponds to that of the aldehyde (active) form of glyceraldehyde 3-phosphate, although in the given conditions the aldehyde leads to diol interconversion is faster than the enzymic reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase. We suggest that above a certain concentration of the enzymes the glyceraldehyde 3-phosphate produced by aldolase gets direct access to glyceraldehyde-3-phosphate dehydrogenase without participating in the aldehyde leads to diol interconversion which otherwise would occur if the substrate were to mix with the bulk medium."}
{"id": "PMID:205416", "title": "Nucleotide sequence of part of the simian virus 40 Hind-D restriction fragment. The presumed initiation region of the VP2 gene.", "content": "The nucleotide sequence at the beginning of the restriction fragment Hind-D from Simian virus 40 DNA has been derived by partial chemical degradation of (5'-32P)-labeled restriction fragments followed by analysis on polyacrylamide gel according to Maxam and Gilbert [Proc. Natl Acad. Sci. U.S.A. 74, 560-564 (1977)]. The sequence reported here is 140 nucleotides long. It contains an ATG codon which presumably corresponds to the initiator codon of the VP2 protein. This codon is preceded by an untranslated region which shows several interesting features, such as an alternation of (dA+dT)-rich and (dG+dC)-rich blocks.", "contents": "Nucleotide sequence of part of the simian virus 40 Hind-D restriction fragment. The presumed initiation region of the VP2 gene. The nucleotide sequence at the beginning of the restriction fragment Hind-D from Simian virus 40 DNA has been derived by partial chemical degradation of (5'-32P)-labeled restriction fragments followed by analysis on polyacrylamide gel according to Maxam and Gilbert [Proc. Natl Acad. Sci. U.S.A. 74, 560-564 (1977)]. The sequence reported here is 140 nucleotides long. It contains an ATG codon which presumably corresponds to the initiator codon of the VP2 protein. This codon is preceded by an untranslated region which shows several interesting features, such as an alternation of (dA+dT)-rich and (dG+dC)-rich blocks."}
{"id": "PMID:205417", "title": "Nucleotide sequence of the simian virus 40 Hind-K restriction fragment.", "content": "The restriction fragment Hind-K represents 4.2% of the genome of Simian virus 40 (SV40) and is located near the middle of the late region. Its nucleotide sequence is reported here. It was mainly established by analysis of transcription products, synthesized by means of Escherichia coli RNA polymerase and nucleoside triphosphates, one of which was (alpha-32P)-labeled. Strand assignment was possible by hybridization of asymmetric, labeled transcripts of total SV40 DNA to filter-bound Hind-K fragment. Further information and unambiguous confirmation of the sequence was obtained by the use of direct DNA-sequencing methods. For this purpose the fragment was labeled at the 5' ends by means of polynucleotide kinase and [gamma-32P]ATP and redigested with a suitable restriction enzyme. The separated products were then either partially digested with snake venom diesterase for analysis by the 'wandering spot' method or partially degraded with the base-specific reagents dimethylsulphate or hydrazine for direct sequence analysis on gel. The Hind-K sequence is 219 base pairs long. The message strand is particularly rich in adenosine (39%) and purines. The nucleotide sequence cna unambiguously be translated into an amino acid sequence and the N-terminal codon of the viral protein VP1 gene could be identified. The amino-terminal part of VP1 is rich in proline and lysine. The nucleotide sequence of Hind-K codes also for the carboxyl-terminal part of the viral protein VP2 and VP3 genes, which partly overlap the VP1 gene.", "contents": "Nucleotide sequence of the simian virus 40 Hind-K restriction fragment. The restriction fragment Hind-K represents 4.2% of the genome of Simian virus 40 (SV40) and is located near the middle of the late region. Its nucleotide sequence is reported here. It was mainly established by analysis of transcription products, synthesized by means of Escherichia coli RNA polymerase and nucleoside triphosphates, one of which was (alpha-32P)-labeled. Strand assignment was possible by hybridization of asymmetric, labeled transcripts of total SV40 DNA to filter-bound Hind-K fragment. Further information and unambiguous confirmation of the sequence was obtained by the use of direct DNA-sequencing methods. For this purpose the fragment was labeled at the 5' ends by means of polynucleotide kinase and [gamma-32P]ATP and redigested with a suitable restriction enzyme. The separated products were then either partially digested with snake venom diesterase for analysis by the 'wandering spot' method or partially degraded with the base-specific reagents dimethylsulphate or hydrazine for direct sequence analysis on gel. The Hind-K sequence is 219 base pairs long. The message strand is particularly rich in adenosine (39%) and purines. The nucleotide sequence cna unambiguously be translated into an amino acid sequence and the N-terminal codon of the viral protein VP1 gene could be identified. The amino-terminal part of VP1 is rich in proline and lysine. The nucleotide sequence of Hind-K codes also for the carboxyl-terminal part of the viral protein VP2 and VP3 genes, which partly overlap the VP1 gene."}
{"id": "PMID:205420", "title": "Lanthanum as a tool to study the role of phosphatidylinositol in the calcium transport in rat parotid glands upon cholinergic stimulation.", "content": "We describe the effects of lanthanum on protein secretion, potassium efflux, calcium uptake and phosphatidylinositol turnover stimulated by cholinergic agonists in rat parotid glands. Carbachol increases in vitro calcium uptake, protein secretion and K+ efflux through muscarinic receptor; however it fails to stimulate protein discharge or K+ release in a incubation medium free of calcium. Lanthanum inhibits calcium uptake, protein secretion and K+ efflux induced by carbachol without impairing protein discharge stimulated by norepinephrine through the beta-adrenergic receptor. Norepinephrine, in the presence of calcium in the incubation medium, stimulates the K+ efflux through the alpha-adrenergic receptor: this effect is suppressed by lanthanum. These results emphasize the role of increased influx of calcium in the cellular phenomena controlled by muscarinic or alpha-adrenergic receptors. Carbachol increases phosphatidylinositol turnover in the absence of calcium in extracellular medium; indeed it is shown that carbachol increases the rate of phosphatidylinositol breakdown and that lanthanum impairs this cholinergic effects. From these data it is suggested that the interaction between cholinergic agonist and muscarinic receptor could induce a stimulation of 'phosphatidylinositol turnover' which could control the calcium influx according to the gradient through the plasmalemma membrane.", "contents": "Lanthanum as a tool to study the role of phosphatidylinositol in the calcium transport in rat parotid glands upon cholinergic stimulation. We describe the effects of lanthanum on protein secretion, potassium efflux, calcium uptake and phosphatidylinositol turnover stimulated by cholinergic agonists in rat parotid glands. Carbachol increases in vitro calcium uptake, protein secretion and K+ efflux through muscarinic receptor; however it fails to stimulate protein discharge or K+ release in a incubation medium free of calcium. Lanthanum inhibits calcium uptake, protein secretion and K+ efflux induced by carbachol without impairing protein discharge stimulated by norepinephrine through the beta-adrenergic receptor. Norepinephrine, in the presence of calcium in the incubation medium, stimulates the K+ efflux through the alpha-adrenergic receptor: this effect is suppressed by lanthanum. These results emphasize the role of increased influx of calcium in the cellular phenomena controlled by muscarinic or alpha-adrenergic receptors. Carbachol increases phosphatidylinositol turnover in the absence of calcium in extracellular medium; indeed it is shown that carbachol increases the rate of phosphatidylinositol breakdown and that lanthanum impairs this cholinergic effects. From these data it is suggested that the interaction between cholinergic agonist and muscarinic receptor could induce a stimulation of 'phosphatidylinositol turnover' which could control the calcium influx according to the gradient through the plasmalemma membrane."}
{"id": "PMID:205421", "title": "The role of cyclic AMP in temperature-dependent changes of contractile force and sensitivity ot isoprenaline and papaverine in guinea-pig atria.", "content": "Right and left guinea-pig atria responded to decreasing temperatures (42-27 degrees C) with elevation for force of contraction and concomitant increases in cAMP. When atria were rapidly cooled from 42 to 27 degrees C the increase in cAMP occurred prior to the onset of the inotropic responses. Papaverine (3 X 10(-5) M) potentiated the effects of temperature on cAMP and force of contraction on left atria driven at 0.5 Hz. On right atria beating spontaneously at frequencies above 2 Hz papaverine only potentiated the effect of decreasing temperatures on the response of cAMP but not on that of force of contraction. Time course studies of the effects of isoprenaline (3 X 10(-8) M) on right atria at 27 degrees C showed large inotropic responses to isoprenaline which were accompanied by increases in cAMP. At 42 degrees C the responses of force of contraction and cAMP to isoprenaline occurred faster and were only short-lasting. As with the time courses for isoprenaline, dose-response curves for the effect of isoprenaline and papaverine on cAMP content and force of contraction also appeared to be shifted towards higher levels at hypothemia. However, pD2 values reflected increases in affinity for inotropic, but not for the cAMP responses to isoprenaline and papaverine at hypothermia. These results show that cyclic AMP is involved in the inotropic responses to hypothermia, but not in the supersensitivity of heart to isoprenaline and papaverine as observed at low temperatures.", "contents": "The role of cyclic AMP in temperature-dependent changes of contractile force and sensitivity ot isoprenaline and papaverine in guinea-pig atria. Right and left guinea-pig atria responded to decreasing temperatures (42-27 degrees C) with elevation for force of contraction and concomitant increases in cAMP. When atria were rapidly cooled from 42 to 27 degrees C the increase in cAMP occurred prior to the onset of the inotropic responses. Papaverine (3 X 10(-5) M) potentiated the effects of temperature on cAMP and force of contraction on left atria driven at 0.5 Hz. On right atria beating spontaneously at frequencies above 2 Hz papaverine only potentiated the effect of decreasing temperatures on the response of cAMP but not on that of force of contraction. Time course studies of the effects of isoprenaline (3 X 10(-8) M) on right atria at 27 degrees C showed large inotropic responses to isoprenaline which were accompanied by increases in cAMP. At 42 degrees C the responses of force of contraction and cAMP to isoprenaline occurred faster and were only short-lasting. As with the time courses for isoprenaline, dose-response curves for the effect of isoprenaline and papaverine on cAMP content and force of contraction also appeared to be shifted towards higher levels at hypothemia. However, pD2 values reflected increases in affinity for inotropic, but not for the cAMP responses to isoprenaline and papaverine at hypothermia. These results show that cyclic AMP is involved in the inotropic responses to hypothermia, but not in the supersensitivity of heart to isoprenaline and papaverine as observed at low temperatures."}
{"id": "PMID:205422", "title": "Increases in plasma cyclic AMP dependent on endogenous catecholamines.", "content": "Administration of tyramine (with or without phentolamine) as well as induction of ether anesthesia or insulin hypoglycemia caused a sharp increase in plasma cyclic AMP in rats. Based on the findings that the treatment of rats with reserpine, 6-hydroxydopamine, cocaine or propranolol totally abolished tyramine-induced increases in plasma cyclic AMP, it was concluded that catecholamines released from sympathetic neuronal terminals by tyramine could activate adenylate cyclase via the stimulation of postsynaptic beta-adrenoceptors. In contrast, catecholamines secreted from adrenal medulla were largely responsible for the increase in plasma cyclic AMP induced by ether anesthesia; whereas glucagon, in addition to adrenal catecholamines, played a significant role in hypoglycemia-induced increases in plasma cyclic AMP. Assay of plasma cyclic AMP following these stimuli is very promising as a test for adrenergic activities in experimental and clinical studies.", "contents": "Increases in plasma cyclic AMP dependent on endogenous catecholamines. Administration of tyramine (with or without phentolamine) as well as induction of ether anesthesia or insulin hypoglycemia caused a sharp increase in plasma cyclic AMP in rats. Based on the findings that the treatment of rats with reserpine, 6-hydroxydopamine, cocaine or propranolol totally abolished tyramine-induced increases in plasma cyclic AMP, it was concluded that catecholamines released from sympathetic neuronal terminals by tyramine could activate adenylate cyclase via the stimulation of postsynaptic beta-adrenoceptors. In contrast, catecholamines secreted from adrenal medulla were largely responsible for the increase in plasma cyclic AMP induced by ether anesthesia; whereas glucagon, in addition to adrenal catecholamines, played a significant role in hypoglycemia-induced increases in plasma cyclic AMP. Assay of plasma cyclic AMP following these stimuli is very promising as a test for adrenergic activities in experimental and clinical studies."}
{"id": "PMID:205423", "title": "Correlation between isoprenaline-stimulated synthesis of cyclic AMP and occurrence of beta-adrenoreceptors in immature erythrocytes from rats.", "content": "When increasing reticulocytosis (up to 80%) was induced in rats by treatment with acetyl-phenylhydrazine (up to 70 mg/kg on 3 consecutive days) synthesis of cAMP stimulated by isoprenaline in intact red blood cells and in the related membrane preparations increased up to 100-fold. At the same time the density of beta-adrenoreceptor sites (measured by ligand binding with (3H)(-)-dihydroalprenolol) in the related membrane preparations was only increased about 5-fold. There was however a linear correlation between the increase of isoprenaline-stimulated enzyme activity and the receptor density in membrane preparations. The results indicate that mature red cells contain beta-adrenoreceptor sites but little or not adenyl cyclase activity. Thus, during the maturation process of these cells, enzyme activity and receptor densities decrease at different speeds indicating a different turnover of these two entities of the cytoplasmic membrane.", "contents": "Correlation between isoprenaline-stimulated synthesis of cyclic AMP and occurrence of beta-adrenoreceptors in immature erythrocytes from rats. When increasing reticulocytosis (up to 80%) was induced in rats by treatment with acetyl-phenylhydrazine (up to 70 mg/kg on 3 consecutive days) synthesis of cAMP stimulated by isoprenaline in intact red blood cells and in the related membrane preparations increased up to 100-fold. At the same time the density of beta-adrenoreceptor sites (measured by ligand binding with (3H)(-)-dihydroalprenolol) in the related membrane preparations was only increased about 5-fold. There was however a linear correlation between the increase of isoprenaline-stimulated enzyme activity and the receptor density in membrane preparations. The results indicate that mature red cells contain beta-adrenoreceptor sites but little or not adenyl cyclase activity. Thus, during the maturation process of these cells, enzyme activity and receptor densities decrease at different speeds indicating a different turnover of these two entities of the cytoplasmic membrane."}
{"id": "PMID:205428", "title": "Exchange of tritium from randomly tritiated taurocholate by microbial bile salt oxidoreductases.", "content": "Tritium distribution on randomly labelled taurocholate (TC) was estimated at 28%, 4%, 1% and less than 0.5% on the hydrogens opposite the 3alpha-, 7alpha- and 12alpha-OH groups and taurine moiety respectively. Anomalously, C. perfringens 3alpha-hydroxysteroid dehydrogenase (3alpha-HSDH) catalyzed tritium loss of 36% on formation of 7alpha-, 12alpha-dihydroxy-3-keto-5beta-cholanoate, implying additional losses of tritium at other sites by this enzyme.", "contents": "Exchange of tritium from randomly tritiated taurocholate by microbial bile salt oxidoreductases. Tritium distribution on randomly labelled taurocholate (TC) was estimated at 28%, 4%, 1% and less than 0.5% on the hydrogens opposite the 3alpha-, 7alpha- and 12alpha-OH groups and taurine moiety respectively. Anomalously, C. perfringens 3alpha-hydroxysteroid dehydrogenase (3alpha-HSDH) catalyzed tritium loss of 36% on formation of 7alpha-, 12alpha-dihydroxy-3-keto-5beta-cholanoate, implying additional losses of tritium at other sites by this enzyme."}
{"id": "PMID:205429", "title": "Inhibition of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary by alrestatin.", "content": "Alrestatin at 25-1 X 10(-4) M inhibited the accumulation of cyclic AMP induced by prostaglandin E2, but not theophylline, in the rat anterior pituitary in vitro. Somatostatin, at lower concentrations, inhibited both; maximal inhibition of the prostaglandin effect was greater with alrestatin. As cyclic AMP is considered to be a mediator in induced-hormonal release, it appears from the present findings that alrestatin may be of potential use in altering hormonal release.", "contents": "Inhibition of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary by alrestatin. Alrestatin at 25-1 X 10(-4) M inhibited the accumulation of cyclic AMP induced by prostaglandin E2, but not theophylline, in the rat anterior pituitary in vitro. Somatostatin, at lower concentrations, inhibited both; maximal inhibition of the prostaglandin effect was greater with alrestatin. As cyclic AMP is considered to be a mediator in induced-hormonal release, it appears from the present findings that alrestatin may be of potential use in altering hormonal release."}
{"id": "PMID:205430", "title": "Neuronal responses to extracellularly applied cyclic AMP:Role of the adenosine receptor.", "content": "At low doses, theophylline blocks the neuronal depressant effects of 5'-AMP, but not cyclic AMP. Higher doses (100 mg/kg) block cyclic AMP responses and reduce the effects of noradrenaline and GABA. It is concluded that cyclic AMP does not depress neurones via the adenosine receptor.", "contents": "Neuronal responses to extracellularly applied cyclic AMP:Role of the adenosine receptor. At low doses, theophylline blocks the neuronal depressant effects of 5'-AMP, but not cyclic AMP. Higher doses (100 mg/kg) block cyclic AMP responses and reduce the effects of noradrenaline and GABA. It is concluded that cyclic AMP does not depress neurones via the adenosine receptor."}
{"id": "PMID:205431", "title": "A synergistic interaction between the teratogenic effect of trypan blue and dietary deficiency in the rat.", "content": "There was an increased incidence, compared to controls, of exencephaly and microphthalmia in the offspring of rats fed a vitamin D deficient diet and injected with trypan blue on day 9 of gestation. Oral vitamin D did not reverse the effect.", "contents": "A synergistic interaction between the teratogenic effect of trypan blue and dietary deficiency in the rat. There was an increased incidence, compared to controls, of exencephaly and microphthalmia in the offspring of rats fed a vitamin D deficient diet and injected with trypan blue on day 9 of gestation. Oral vitamin D did not reverse the effect."}
{"id": "PMID:205435", "title": "Interactions between age and the neuroendocrine and immune systems.", "content": "Three conclusions are suggested by some of the recent work on aging, immunology and the neuroendocrine system. 1) There appears to be sufficient data to implicate the neuroendocrine system in both the maturation and the senescence of at least some components of the immune system. 2) The thymus by its presence or its absence appears to influence certain functions of the pituitary; thus, there appears to be a possible reciprocal relationship between the pituitary and the thymus. 3) Changes in the levels of pituitary hormones or hormones that are controlled by the pituitary can restore in older rats and mice certain functions that are generally considered as part of the immune surveillance and defense system. Consequently, it can be hoped that further studies of neuroendocrine-immune relationships might lead to an understanding of some of the causes for the decline in immune competence with age in mammals.", "contents": "Interactions between age and the neuroendocrine and immune systems. Three conclusions are suggested by some of the recent work on aging, immunology and the neuroendocrine system. 1) There appears to be sufficient data to implicate the neuroendocrine system in both the maturation and the senescence of at least some components of the immune system. 2) The thymus by its presence or its absence appears to influence certain functions of the pituitary; thus, there appears to be a possible reciprocal relationship between the pituitary and the thymus. 3) Changes in the levels of pituitary hormones or hormones that are controlled by the pituitary can restore in older rats and mice certain functions that are generally considered as part of the immune surveillance and defense system. Consequently, it can be hoped that further studies of neuroendocrine-immune relationships might lead to an understanding of some of the causes for the decline in immune competence with age in mammals."}
{"id": "PMID:205437", "title": "The morphology of interneuronal synaptogenesis: a review.", "content": "This review has endeavored to present current findings on the morphology of synaptogenesis, summarized in Fig. 5. Though much has been discovered about the order of events and the origin of organelles, the crucial questions of why these events occur at the moment in space and time remain largely unanswered. For an understanding of the molecular basis of neuronal recognition, and of the assembly and maintenance of a functional synaptic active zone, further extensive multidisciplinary studies will be necessary.", "contents": "The morphology of interneuronal synaptogenesis: a review. This review has endeavored to present current findings on the morphology of synaptogenesis, summarized in Fig. 5. Though much has been discovered about the order of events and the origin of organelles, the crucial questions of why these events occur at the moment in space and time remain largely unanswered. For an understanding of the molecular basis of neuronal recognition, and of the assembly and maintenance of a functional synaptic active zone, further extensive multidisciplinary studies will be necessary."}
{"id": "PMID:205438", "title": "Interactions between neurons and their targets during in vivo synaptogenesis.", "content": "In vivo synaptogenesis is described in a simple vertebrate system, the chick ciliary ganglion, a parasympathetic autonomic ganglion. An attempt is made to integrate anatomical, physiological and biochemical observations during synapse formation in the ganglion and in the peripheral target structures; the iris, ciliary muscle, and smooth muscle of the choroid coat. The relationship between synaptogenesis and neuron survival is explored, and it is shown that a critically timed interaction between the neuron and target organ is necessary for full neuronal maturation and survival. The existence of an active competition between neurons for survival is documented, and the possible relationship between neuronal cell death and specificity of connections is discussed.", "contents": "Interactions between neurons and their targets during in vivo synaptogenesis. In vivo synaptogenesis is described in a simple vertebrate system, the chick ciliary ganglion, a parasympathetic autonomic ganglion. An attempt is made to integrate anatomical, physiological and biochemical observations during synapse formation in the ganglion and in the peripheral target structures; the iris, ciliary muscle, and smooth muscle of the choroid coat. The relationship between synaptogenesis and neuron survival is explored, and it is shown that a critically timed interaction between the neuron and target organ is necessary for full neuronal maturation and survival. The existence of an active competition between neurons for survival is documented, and the possible relationship between neuronal cell death and specificity of connections is discussed."}
{"id": "PMID:205445", "title": "Effect of two phosphodiesterase inhibitors, cyclic adenosine 3':5'-monophosphate, and a beta-blocking agent on human sperm motility.", "content": "Mann-fructose fluid (MF), and MF plus caffeine, MF plus pentoxifylline, MF (dibutyryl cAMP), MF plus propranolol, and MF plus propranolol plus dibutyryl cAMP were individually added to aliquots of semen samples obtained from 18 normal men. These drugs were added to a final concentration of 0.6 mM. One aliquot with no addition served as control. Samples were incubated at 37 degrees C and observed by light microscopy at 30 minutes and at 1,2, and 4 hours after obtained the material. At each observation time, semen quality was evaluated by determinating the percentages of forwardly progresssive spermatozoa, slowly progressive spermatozoa, \"in situ\" motile spermatozoa, live and nonmotile spermatozoa, and dead spermatozoa. Mann-fructose fluid resulted in a decrease in motility and the duration of activity of spermatozoa, Caffeine seemed to neutralize the deleterus effect on the buffer, whereas pentoxifylline and cAMP seemed to increase the duration of activity of spermatozoa. Propranolol resulted in a dramatic decrease in motility, an effect that could not be neutralized by the simultaneous addition of cAMP.", "contents": "Effect of two phosphodiesterase inhibitors, cyclic adenosine 3':5'-monophosphate, and a beta-blocking agent on human sperm motility. Mann-fructose fluid (MF), and MF plus caffeine, MF plus pentoxifylline, MF (dibutyryl cAMP), MF plus propranolol, and MF plus propranolol plus dibutyryl cAMP were individually added to aliquots of semen samples obtained from 18 normal men. These drugs were added to a final concentration of 0.6 mM. One aliquot with no addition served as control. Samples were incubated at 37 degrees C and observed by light microscopy at 30 minutes and at 1,2, and 4 hours after obtained the material. At each observation time, semen quality was evaluated by determinating the percentages of forwardly progresssive spermatozoa, slowly progressive spermatozoa, \"in situ\" motile spermatozoa, live and nonmotile spermatozoa, and dead spermatozoa. Mann-fructose fluid resulted in a decrease in motility and the duration of activity of spermatozoa, Caffeine seemed to neutralize the deleterus effect on the buffer, whereas pentoxifylline and cAMP seemed to increase the duration of activity of spermatozoa. Propranolol resulted in a dramatic decrease in motility, an effect that could not be neutralized by the simultaneous addition of cAMP."}
{"id": "PMID:205448", "title": "[Interaction of catecholamines and corticosteroids during the process of muscle fatigue].", "content": "After prolonged (8 hrs) swimming, the level of corticosteroids was reduced and the contents of aldosterone and DOC in the blood was increased in the rats. At incubation of these rats' adrenals in the L-thyrosine substratum the synthesis of adrenaline was reduced. Addition of hydrocortisone, prednisolone and corticosterone into the medium as well as in vivo administration of these increased the adrenaline synthesis in swimming rats and did not alter it in intact rats. Neither in vitro addition of aldosterone nor in vivo administration of ACTH activated the process. The activating effect of glucocorticoids was absent at incubation of the adrenals with L-DOPA and L-noradrenaline. Synthesis of cathecholamines in the heart of swimming rats in the presence of L-thyrosine and L-DOPA as precnrsors was suppressed; neither was it restored by administration of corticosteroids both in vitro and in vivo. This suggests that one of the reasons for suppression of the catecholamine synthesis in adrenals at obvious physical fatigue is the decrease of the glucocorticoid activity.", "contents": "[Interaction of catecholamines and corticosteroids during the process of muscle fatigue]. After prolonged (8 hrs) swimming, the level of corticosteroids was reduced and the contents of aldosterone and DOC in the blood was increased in the rats. At incubation of these rats' adrenals in the L-thyrosine substratum the synthesis of adrenaline was reduced. Addition of hydrocortisone, prednisolone and corticosterone into the medium as well as in vivo administration of these increased the adrenaline synthesis in swimming rats and did not alter it in intact rats. Neither in vitro addition of aldosterone nor in vivo administration of ACTH activated the process. The activating effect of glucocorticoids was absent at incubation of the adrenals with L-DOPA and L-noradrenaline. Synthesis of cathecholamines in the heart of swimming rats in the presence of L-thyrosine and L-DOPA as precnrsors was suppressed; neither was it restored by administration of corticosteroids both in vitro and in vivo. This suggests that one of the reasons for suppression of the catecholamine synthesis in adrenals at obvious physical fatigue is the decrease of the glucocorticoid activity."}
{"id": "PMID:205453", "title": "Worldwide controversies in gestational trophoblastic neoplasms.", "content": "This article reviews worldwide controversies concerning gestational trophoblastic neoplasms (hydatidiform mole, invasive mole, and choriocarcinoma). The epidemiology, endocrinology, histopathologic grading, classification, diagnosis, treatment, management and follow-up (including chemotherapy, irradiation, and immunotherapy) of gestational trophoblastic neoplasms - particularly molar pregnancies - are discussed; and ways to help create a standardized classification system and provide optimal treatment for each type of patient are suggested.", "contents": "Worldwide controversies in gestational trophoblastic neoplasms. This article reviews worldwide controversies concerning gestational trophoblastic neoplasms (hydatidiform mole, invasive mole, and choriocarcinoma). The epidemiology, endocrinology, histopathologic grading, classification, diagnosis, treatment, management and follow-up (including chemotherapy, irradiation, and immunotherapy) of gestational trophoblastic neoplasms - particularly molar pregnancies - are discussed; and ways to help create a standardized classification system and provide optimal treatment for each type of patient are suggested."}
{"id": "PMID:205474", "title": "Lack of effect of bile in pathogenesis of secretion in mechanical small bowel obstruction.", "content": "In dogs, the principal lesion in the ileal mucosa above a mechanical obstruction is the induction of a secretory state in which there is a net loss of water and electrolytes into the intestinal lumen. The role of stagnated bile as a possible agent provoking this secretion was explored by ligating the common bile duct and diverting the bile by means of an anastomosis between the gall bladder and the ileum distal to the obstruction. 7 days after creation of an obstruction with bile diversion, the functional and morphological changes in the obstructed loop were almost identical to those occurring in animals with obstructions without bile diversion. The secretory response above the obstruction continued unabated, with levels of cAMP in the secreting mucosae lower than in control tissues. These results suggest: (a) that the secretion in the obstructed intestine is not influenced by the presence of bile, and (b) that this secretion may not be secondary to an increase in mucosal cAMP levels.", "contents": "Lack of effect of bile in pathogenesis of secretion in mechanical small bowel obstruction. In dogs, the principal lesion in the ileal mucosa above a mechanical obstruction is the induction of a secretory state in which there is a net loss of water and electrolytes into the intestinal lumen. The role of stagnated bile as a possible agent provoking this secretion was explored by ligating the common bile duct and diverting the bile by means of an anastomosis between the gall bladder and the ileum distal to the obstruction. 7 days after creation of an obstruction with bile diversion, the functional and morphological changes in the obstructed loop were almost identical to those occurring in animals with obstructions without bile diversion. The secretory response above the obstruction continued unabated, with levels of cAMP in the secreting mucosae lower than in control tissues. These results suggest: (a) that the secretion in the obstructed intestine is not influenced by the presence of bile, and (b) that this secretion may not be secondary to an increase in mucosal cAMP levels."}
{"id": "PMID:205475", "title": "Actions of salbutamol in late pregnancy: plasma cyclic AMP, insulin and C-peptide, carbohydrate and lipid metabolites in diabetic and non-diabetic women.", "content": "Salbutamol was administered intravenously in dose increasing from 3.75 to 22.5 microgram/min to 5 non-diabetic and 7 diabetic women in the last trimester of pregnancy. In diabetic as well as non-diabetic women the diastolic blood pressure fell progressively with increasing doses, and the systolic BP and heart rate increased at doses above 7.5 microgram/min. The effect of fetal heart rate was less pronounced than the effect on maternal heart rate. Cyclic AMP levels in plasma were similar in non-diabetic and diabetic women before salbutamol. Twenty min following 3.75 microgram/min a significant increase was seen in both groups. The peak increase (3-5 fold) was higher in the diabetic than in the non-diabetic women. Plasma insulin and C-peptide levels rose in a dose-dependent manner in the non-diabetic and four of the diabetic women. However, in three of the diabetic women the insulin level was unaffected by salbutamol and C-peptide was almost undetectable. Plasma concentrations of glucose, glycerol, NEFA and 3-HB were higher in the diabetics than in the non-diabetics before salbutamol and the elevations induced by salbutamol were also significantly larger in the diabetic women. The present data show that salbutamol in doses employed clinically may cause pronounced metabolic effects, especially in diabetic women, and it is suggested that when intravenous infusion of salbutamol is given to pregnant diabetic women not only cardiovascular but also some metabolic variable such as glucose should be carefully monitored.", "contents": "Actions of salbutamol in late pregnancy: plasma cyclic AMP, insulin and C-peptide, carbohydrate and lipid metabolites in diabetic and non-diabetic women. Salbutamol was administered intravenously in dose increasing from 3.75 to 22.5 microgram/min to 5 non-diabetic and 7 diabetic women in the last trimester of pregnancy. In diabetic as well as non-diabetic women the diastolic blood pressure fell progressively with increasing doses, and the systolic BP and heart rate increased at doses above 7.5 microgram/min. The effect of fetal heart rate was less pronounced than the effect on maternal heart rate. Cyclic AMP levels in plasma were similar in non-diabetic and diabetic women before salbutamol. Twenty min following 3.75 microgram/min a significant increase was seen in both groups. The peak increase (3-5 fold) was higher in the diabetic than in the non-diabetic women. Plasma insulin and C-peptide levels rose in a dose-dependent manner in the non-diabetic and four of the diabetic women. However, in three of the diabetic women the insulin level was unaffected by salbutamol and C-peptide was almost undetectable. Plasma concentrations of glucose, glycerol, NEFA and 3-HB were higher in the diabetics than in the non-diabetics before salbutamol and the elevations induced by salbutamol were also significantly larger in the diabetic women. The present data show that salbutamol in doses employed clinically may cause pronounced metabolic effects, especially in diabetic women, and it is suggested that when intravenous infusion of salbutamol is given to pregnant diabetic women not only cardiovascular but also some metabolic variable such as glucose should be carefully monitored."}
{"id": "PMID:205476", "title": "Hepatic insulin responsiveness in patients with endogenous hypertriglyceridaemia.", "content": "Plasma insulin response to oral glucose, insulin resistance, and insulin suppression of hepatic glucose production were studied in 11 normal subjects and 11 hypertriglyceridaemic patients. Patients with hypertriglyceridaemia had a significantly higher insulin response to oral glucose. Insulin resistance was also significantly greater in hypertriglyceridaemic subjects as determined by measuring the steady-state plasma glucose response during a continuous infusion of epinephrine, propranolol, glucose, and exogenous insulin. Insulin suppression of hepatic glucose production was calculated from the results of two studies in which glucose turnover rate was measured by a continuous infusion of 3H-2-glucose. The first study was performed under conditions of basal insulin secretion, and the second carried out at steady state exogenous insulin levels of approximately 100 muU/ml. The results indicated that basal hepatic glucose production was the same in both groups, and was suppressed to an equal degree by physiological levels of insulin. These data demonstrate that hepatic glucose production can be suppressed to an equal degree in normal and hypertriglyceridaemic subjects at comparable circulating insulin levels, at the same time that resistance to insulin-stimulated glucose uptake is observed in the hypertriglyceridaemic individuals.", "contents": "Hepatic insulin responsiveness in patients with endogenous hypertriglyceridaemia. Plasma insulin response to oral glucose, insulin resistance, and insulin suppression of hepatic glucose production were studied in 11 normal subjects and 11 hypertriglyceridaemic patients. Patients with hypertriglyceridaemia had a significantly higher insulin response to oral glucose. Insulin resistance was also significantly greater in hypertriglyceridaemic subjects as determined by measuring the steady-state plasma glucose response during a continuous infusion of epinephrine, propranolol, glucose, and exogenous insulin. Insulin suppression of hepatic glucose production was calculated from the results of two studies in which glucose turnover rate was measured by a continuous infusion of 3H-2-glucose. The first study was performed under conditions of basal insulin secretion, and the second carried out at steady state exogenous insulin levels of approximately 100 muU/ml. The results indicated that basal hepatic glucose production was the same in both groups, and was suppressed to an equal degree by physiological levels of insulin. These data demonstrate that hepatic glucose production can be suppressed to an equal degree in normal and hypertriglyceridaemic subjects at comparable circulating insulin levels, at the same time that resistance to insulin-stimulated glucose uptake is observed in the hypertriglyceridaemic individuals."}
{"id": "PMID:205477", "title": "Epstein-Barr virus-determined nuclear antigen in malignant epithelial cells of nasopharyngeal carcinoma.", "content": "Tumor tissue from lymph node metastasis of nasopharyngeal carcinoma (NPC) was successfully heterotransplanted into an athymic nude mouse and the tumor grown in the nude mouse was identical in its morphology to that form the patient by optical and electron microscopy. Tumor cells at passage 2 were dispersed in vitro by enzymic digestion and smeared. Epstein-Barr virus-determined nuclear antigen (EBNA) was demonstrated in malignant epithelial cells of the smear.", "contents": "Epstein-Barr virus-determined nuclear antigen in malignant epithelial cells of nasopharyngeal carcinoma. Tumor tissue from lymph node metastasis of nasopharyngeal carcinoma (NPC) was successfully heterotransplanted into an athymic nude mouse and the tumor grown in the nude mouse was identical in its morphology to that form the patient by optical and electron microscopy. Tumor cells at passage 2 were dispersed in vitro by enzymic digestion and smeared. Epstein-Barr virus-determined nuclear antigen (EBNA) was demonstrated in malignant epithelial cells of the smear."}
{"id": "PMID:205478", "title": "Antitumor activity of a new amino acid derivative, N6,N9-bis-(butyloxycarbonylaminomethyl)-L-citrulline.", "content": "Approximately 800 amino acid derivatives have been synthesized and screened in order to evaluate their antitumor activity against various transplantable rat ascites hepatomas. Among them, N6,N9-bis(butyloxycarbonylaminomethyl)-L-citrulline (A-924) was found to be highly effective against various rat ascites hepatomas. A-924, when given orally, exhibited prolongation of survival of rats implanted intravenously with ascites hepatoma cells such as AH-44, AH-66, AH-130, AH-66F, or AH-41C.", "contents": "Antitumor activity of a new amino acid derivative, N6,N9-bis-(butyloxycarbonylaminomethyl)-L-citrulline. Approximately 800 amino acid derivatives have been synthesized and screened in order to evaluate their antitumor activity against various transplantable rat ascites hepatomas. Among them, N6,N9-bis(butyloxycarbonylaminomethyl)-L-citrulline (A-924) was found to be highly effective against various rat ascites hepatomas. A-924, when given orally, exhibited prolongation of survival of rats implanted intravenously with ascites hepatoma cells such as AH-44, AH-66, AH-130, AH-66F, or AH-41C."}
{"id": "PMID:205481", "title": "X-linked and autosomal genes controlling mouse alpha-galactosidase expression.", "content": "Analysis of F2 and backcross animals has confirmed the X-chromosome linkage of Ags, the structural locus for mouse alpha-galactosidase. The position of Ags has been located in the X chromosome, 9 centimorgans from Mo, and the gene order is centromere-Hq-Bn-Ta-Mo-Ags. A variation in the developmental expression of alpha-galactosidase activity, inherited as an autosomal trait, has been characterized using recombinant inbred lines of mice. Among certain recombinant inbred lines, the variation appears to segregate as a single major locus.", "contents": "X-linked and autosomal genes controlling mouse alpha-galactosidase expression. Analysis of F2 and backcross animals has confirmed the X-chromosome linkage of Ags, the structural locus for mouse alpha-galactosidase. The position of Ags has been located in the X chromosome, 9 centimorgans from Mo, and the gene order is centromere-Hq-Bn-Ta-Mo-Ags. A variation in the developmental expression of alpha-galactosidase activity, inherited as an autosomal trait, has been characterized using recombinant inbred lines of mice. Among certain recombinant inbred lines, the variation appears to segregate as a single major locus."}
{"id": "PMID:205482", "title": "Heterozygous effects on fitness of EMS-treated chromosomes in Drosophila melanogaster.", "content": "The heterozygous effects on fitness of second chromosomes carrying mutants induced with different doses of EMS were ascertained by monitoring changes in chromosome frequencies over time. These changes were observed in populations in which the treated chromosomes, as well as untreated competitors, remained heterozygous in males generation after generation. This situation was achieved by using a translocation which links the second chromosome to the X chromosome; however, only untranslocated second chromosomes were mutagenized. Chromosomes were classified according to their effects on viability in homozygous condition. A preliminary homozygosis identified completely lethal chromosomes; secondary tests distinguished between drastic (viability index < 0.1) and nondrastic chromosomes. Chromosomes that were nondrastic after treatment were found to reduce the fitness of their heterozygous carriers by 3-5%. The data show that flies homozygous for these chromosomes were about 2.7% less viable per treatment with 1 mm EMS than flies homozygous for untreated chromosomes. By comparing the fitness-depressing effects of nondrastic EMS-induced mutants in heterozygous condition with the corresponding viability-depressing effects measured by Temin, it is apparent that the total fitness effects are several times larger than the viability effects alone. Completely lethal chromosomes derived from the most heavily treated material reduced fitness by 11% in heterozygous condition; approximately half of this reduction was due to the lethal mutations themselves.", "contents": "Heterozygous effects on fitness of EMS-treated chromosomes in Drosophila melanogaster. The heterozygous effects on fitness of second chromosomes carrying mutants induced with different doses of EMS were ascertained by monitoring changes in chromosome frequencies over time. These changes were observed in populations in which the treated chromosomes, as well as untreated competitors, remained heterozygous in males generation after generation. This situation was achieved by using a translocation which links the second chromosome to the X chromosome; however, only untranslocated second chromosomes were mutagenized. Chromosomes were classified according to their effects on viability in homozygous condition. A preliminary homozygosis identified completely lethal chromosomes; secondary tests distinguished between drastic (viability index < 0.1) and nondrastic chromosomes. Chromosomes that were nondrastic after treatment were found to reduce the fitness of their heterozygous carriers by 3-5%. The data show that flies homozygous for these chromosomes were about 2.7% less viable per treatment with 1 mm EMS than flies homozygous for untreated chromosomes. By comparing the fitness-depressing effects of nondrastic EMS-induced mutants in heterozygous condition with the corresponding viability-depressing effects measured by Temin, it is apparent that the total fitness effects are several times larger than the viability effects alone. Completely lethal chromosomes derived from the most heavily treated material reduced fitness by 11% in heterozygous condition; approximately half of this reduction was due to the lethal mutations themselves."}
{"id": "PMID:205483", "title": "[Operon study of riboflavin biosynthesis in Bacillus subtilis. XII. The determination of the ATP:riboflavin-5'-phosphotransferase and riboflavinsynthetase content in the cells with varying genotypes].", "content": "Activities of riboflavinkinase and riboflavinsynthetase were measured in 15 strains of Bacillus subtilis with different genotype. The increased level of riboflavinkinase was observed in strains, resistant to lumiflavin or lumichrome. Specific activity of riboflavinkinase was found to be about 100 times lower than that of riboflavinsynthetase. The regulation of biosynthesis of these enzymes seems to proceed non-coordinately. This phenomenon can be the sequence of the existence of many operators, controlling the flavinogenesis in Bac. subtilis.", "contents": "[Operon study of riboflavin biosynthesis in Bacillus subtilis. XII. The determination of the ATP:riboflavin-5'-phosphotransferase and riboflavinsynthetase content in the cells with varying genotypes]. Activities of riboflavinkinase and riboflavinsynthetase were measured in 15 strains of Bacillus subtilis with different genotype. The increased level of riboflavinkinase was observed in strains, resistant to lumiflavin or lumichrome. Specific activity of riboflavinkinase was found to be about 100 times lower than that of riboflavinsynthetase. The regulation of biosynthesis of these enzymes seems to proceed non-coordinately. This phenomenon can be the sequence of the existence of many operators, controlling the flavinogenesis in Bac. subtilis."}
{"id": "PMID:205484", "title": "[Genetic control over 7 Lpm-system allotypes of very high-density serum alpha2-lipoprotein the mink].", "content": "Population and hybridological analyses have demonstrated that the alloantigenic markers of very high density alpha2-lipoprotein of mink serum, Lpm7 and Lpm8, along with Lpm1, Lpm2, Lpm3, Lpm4, Lpm5, belong to a common immunogenetic system. 21 Lpm-phenotypes are determined at least by 36 genotypes; each of the 11 phenotypes is conditioned by a single genotype, each of the remaining 10 are conditioned by 2, 3 or 4 genotypes. The Lpm allotypes and allogroups are coded by the genetic units Lpm8, Lpm4, Lpm4,8, Lpm4,7, Lpm3,4,8, Lpm1,8, Lpm1,2,7, Lpm2,4,5,7, which behave as alleles. The last, six seem to be haploid sets of closely linked genes.", "contents": "[Genetic control over 7 Lpm-system allotypes of very high-density serum alpha2-lipoprotein the mink]. Population and hybridological analyses have demonstrated that the alloantigenic markers of very high density alpha2-lipoprotein of mink serum, Lpm7 and Lpm8, along with Lpm1, Lpm2, Lpm3, Lpm4, Lpm5, belong to a common immunogenetic system. 21 Lpm-phenotypes are determined at least by 36 genotypes; each of the 11 phenotypes is conditioned by a single genotype, each of the remaining 10 are conditioned by 2, 3 or 4 genotypes. The Lpm allotypes and allogroups are coded by the genetic units Lpm8, Lpm4, Lpm4,8, Lpm4,7, Lpm3,4,8, Lpm1,8, Lpm1,2,7, Lpm2,4,5,7, which behave as alleles. The last, six seem to be haploid sets of closely linked genes."}
{"id": "PMID:205493", "title": "[Spectral studies of drug interactions with hemoglobin and cytochrome c (author's transl)].", "content": "We studied the drug-induced spectra of hemoglobin and cytochrome c using aniline, aminopyrine, hydrocortisone and prednisolone. The difference spectrum of methemoglobin induced by aniline or aminopyrine was similar to type II, and that of oxidized cytochrome c induced by aniline was similar to type I. Characteristic spectral change occurred with addition of hydrocortisone or prednisolone to each of methemoglobin, oxyhemoglobin and carboxyhemoglobin, and by addition of each drug to deoxyhemoglobin, respectively. Other spectral changes were attributed to oxidation-reduction reactions between the drugs and the hemoproteins. Each of the reduced forms of hemoglobin showed a higher affinity to aniline and aminopyrine than did methemoglobin. Each of the reduced forms of hemoglobin or reduced cytochrome c showed a higher affinity to aminopyrine than to aniline. It is interesting that not only cytochrome P-450, a hydrophobic hemoprotein, but also hemoglobin and cytochrome c, hydrophilic hemoproteins, showed the drug-induced difference spectra. These results suggest direct interactions between drugs and hemoproteins. Oxyhemoglobin had a lower affinity to drugs in hemolysate than in the buffer only.", "contents": "[Spectral studies of drug interactions with hemoglobin and cytochrome c (author's transl)]. We studied the drug-induced spectra of hemoglobin and cytochrome c using aniline, aminopyrine, hydrocortisone and prednisolone. The difference spectrum of methemoglobin induced by aniline or aminopyrine was similar to type II, and that of oxidized cytochrome c induced by aniline was similar to type I. Characteristic spectral change occurred with addition of hydrocortisone or prednisolone to each of methemoglobin, oxyhemoglobin and carboxyhemoglobin, and by addition of each drug to deoxyhemoglobin, respectively. Other spectral changes were attributed to oxidation-reduction reactions between the drugs and the hemoproteins. Each of the reduced forms of hemoglobin showed a higher affinity to aniline and aminopyrine than did methemoglobin. Each of the reduced forms of hemoglobin or reduced cytochrome c showed a higher affinity to aminopyrine than to aniline. It is interesting that not only cytochrome P-450, a hydrophobic hemoprotein, but also hemoglobin and cytochrome c, hydrophilic hemoproteins, showed the drug-induced difference spectra. These results suggest direct interactions between drugs and hemoproteins. Oxyhemoglobin had a lower affinity to drugs in hemolysate than in the buffer only."}
{"id": "PMID:205495", "title": "[Hepatology and immunology].", "content": "Immunologic diseases of the liver are exogenous mostly initiated by virus or endogenous initiated by autoaggression. All virus-induced kinds of hepatitis are due to an immune response against inocculated hepatocytes. Therefore the hepatitis is limited to the period of complete elimination of virus-infected cells. A strong immune response therefore corresponds with an acute and short hepatitis whilest a weak immune response develops a chronic hepatitis. In contrast, autoimmune hepatitis based on a disorder of the immune system with some genetic background is always unlimited. Each cirrhosis developing from immunologic hepatitis is also an immunologic disease; a special variant is the autoimmune primary biliary cirrhosis. All in all, the number of immunologic liver diseases surmounts the remaining liver diseases due to intoxication of metabolic disorders.", "contents": "[Hepatology and immunology]. Immunologic diseases of the liver are exogenous mostly initiated by virus or endogenous initiated by autoaggression. All virus-induced kinds of hepatitis are due to an immune response against inocculated hepatocytes. Therefore the hepatitis is limited to the period of complete elimination of virus-infected cells. A strong immune response therefore corresponds with an acute and short hepatitis whilest a weak immune response develops a chronic hepatitis. In contrast, autoimmune hepatitis based on a disorder of the immune system with some genetic background is always unlimited. Each cirrhosis developing from immunologic hepatitis is also an immunologic disease; a special variant is the autoimmune primary biliary cirrhosis. All in all, the number of immunologic liver diseases surmounts the remaining liver diseases due to intoxication of metabolic disorders."}
{"id": "PMID:205496", "title": "[Lesions of the peripheral nerves in Wilson's disease. Electrodiagnostic findings (author's transl)].", "content": "Electrodiagnostical studies were carried out on three patients with Wilson's disease. The motor nerve conduction velocity was low but not markedly decreased. Some values of the sensory conduction velocity were decreased; the sensory action potentials showed low amplitudes and contained large amounts of late phases. Also, the electromyogram of one female patient showed denervation in the begin of treatment. There are no indications of polyneuropathy in Wilson's disease in the literature. There have been histological reports, however, which indicated lesions of the peripheral nerves in Wilson's disease as our own electrodiagnostical findings do.", "contents": "[Lesions of the peripheral nerves in Wilson's disease. Electrodiagnostic findings (author's transl)]. Electrodiagnostical studies were carried out on three patients with Wilson's disease. The motor nerve conduction velocity was low but not markedly decreased. Some values of the sensory conduction velocity were decreased; the sensory action potentials showed low amplitudes and contained large amounts of late phases. Also, the electromyogram of one female patient showed denervation in the begin of treatment. There are no indications of polyneuropathy in Wilson's disease in the literature. There have been histological reports, however, which indicated lesions of the peripheral nerves in Wilson's disease as our own electrodiagnostical findings do."}
{"id": "PMID:205498", "title": "Histologic classification of pure primary epithelial breast cancer.", "content": "Current classifications of breast cancer are based on either morphologic descriptive or histogenetic criteria. The positive features and shortcomings of the most commonly used systems are presented. Our knowledge of breast cancer leads validity to a histogenetic topographic classification, a modification of which is suggested.", "contents": "Histologic classification of pure primary epithelial breast cancer. Current classifications of breast cancer are based on either morphologic descriptive or histogenetic criteria. The positive features and shortcomings of the most commonly used systems are presented. Our knowledge of breast cancer leads validity to a histogenetic topographic classification, a modification of which is suggested."}
{"id": "PMID:205499", "title": "Ultrastructure of malignant histiocytoma arising in the acromion.", "content": "The ultrastructural features of a malignant histiocytoma of the acromial process of the scapula were studied. Material was obtained from two surgical biopsy specimens and an amputation specimen from the tumor. Cells possessing characteristics of histiocytes, fibroblasts, xanthoma cells, and multinucleated giant cells were present throughout the tumor. Smaller numbers of undifferentiated cells  and lymphocytes were also observed. Intimate cytoplasmic interdigitations between adjacent tumor cells were found, and instances of degenerating intracytoplasmic cells, possibly representing phagocytosis, were observed. Specimens stained with periodic acid-Schiff reagent with and without exposure to diastase, examined by light microscopy, showed that numerous cells contained phagocytized material consisting of degenerating cells rather than cytoplasmic glycogen. Intraumor lymphocytes apparently represented an inflammatory reaction to the tumor. The tumor giant cells and xanthoma cells were probably modified histiocytes. Results of the study were compared with previous reports of ultrastructural studies of malignant histiocytoma of soft tissues. Fundamental similarities between such studies and this one suggested that the progenitor cell is a histiocyte, whether arising in bone or in soft tissues, and that the progenitor cell is capable of differentiation in both histiocytic and fibroblastic directions.", "contents": "Ultrastructure of malignant histiocytoma arising in the acromion. The ultrastructural features of a malignant histiocytoma of the acromial process of the scapula were studied. Material was obtained from two surgical biopsy specimens and an amputation specimen from the tumor. Cells possessing characteristics of histiocytes, fibroblasts, xanthoma cells, and multinucleated giant cells were present throughout the tumor. Smaller numbers of undifferentiated cells  and lymphocytes were also observed. Intimate cytoplasmic interdigitations between adjacent tumor cells were found, and instances of degenerating intracytoplasmic cells, possibly representing phagocytosis, were observed. Specimens stained with periodic acid-Schiff reagent with and without exposure to diastase, examined by light microscopy, showed that numerous cells contained phagocytized material consisting of degenerating cells rather than cytoplasmic glycogen. Intraumor lymphocytes apparently represented an inflammatory reaction to the tumor. The tumor giant cells and xanthoma cells were probably modified histiocytes. Results of the study were compared with previous reports of ultrastructural studies of malignant histiocytoma of soft tissues. Fundamental similarities between such studies and this one suggested that the progenitor cell is a histiocyte, whether arising in bone or in soft tissues, and that the progenitor cell is capable of differentiation in both histiocytic and fibroblastic directions."}
{"id": "PMID:205502", "title": "Pharmacological control of the hormonally modulated immune response. II. Blockade of antibody production by a combination of drugs acting on neuroendocrine functions. Its prevention by gonadotropins and corticotrophin.", "content": "Injection of a combination of three drugs, 5-hydroxytryptophan, the alpha-blocker phentolamine and the neuroleptic drug haloperidol into mice before or together with sheep red blood cells (SRBC) induces a complete and long-lasting inhibition of antibody production to SRBC and leads to specific unresponsiveness. The mice unresponsive to SRBC respond normally to another antigen. Treatment with a combination of luteotropic (LH), follicle stimulating (FSH) and corticotropic hormone (ACTH) before administration of drugs and antigen prevents the immune blockade. Injection of SRBC induces an early elevation of LH in blood. This effect is prevented by previous administration of the three drugs in combination. The hormonal response to a second injection of the same antigen of mice previously made 'unresponsive' is different from that of immunized animals. The suppression of these hormonal changes which follow antigen injection by drugs acting on neuroendocrine regulation and cell membrane adrenergic receptors represents a step forward in efforts aimed at a pharmacological control of acquired immunity.", "contents": "Pharmacological control of the hormonally modulated immune response. II. Blockade of antibody production by a combination of drugs acting on neuroendocrine functions. Its prevention by gonadotropins and corticotrophin. Injection of a combination of three drugs, 5-hydroxytryptophan, the alpha-blocker phentolamine and the neuroleptic drug haloperidol into mice before or together with sheep red blood cells (SRBC) induces a complete and long-lasting inhibition of antibody production to SRBC and leads to specific unresponsiveness. The mice unresponsive to SRBC respond normally to another antigen. Treatment with a combination of luteotropic (LH), follicle stimulating (FSH) and corticotropic hormone (ACTH) before administration of drugs and antigen prevents the immune blockade. Injection of SRBC induces an early elevation of LH in blood. This effect is prevented by previous administration of the three drugs in combination. The hormonal response to a second injection of the same antigen of mice previously made 'unresponsive' is different from that of immunized animals. The suppression of these hormonal changes which follow antigen injection by drugs acting on neuroendocrine regulation and cell membrane adrenergic receptors represents a step forward in efforts aimed at a pharmacological control of acquired immunity."}
{"id": "PMID:205505", "title": "Myeloperoxidase-Cl--H2O2 bactericidal system: effect of bacterial membrane structure and growth conditions.", "content": "The human-myeloperoxidase-Cl--H2O2 bactericidal system killed (i) smooth Enterobacteria spp. greater than or equal to rough and (ii) static-grown, stationary-phase bacteria greater than or equal to aerated-grown, log-phase. This is in contrast to human neutrophil granule extracts (involved in nonoxidative bactericidal mechanisms) that kill rough and aerated log-phase Enterobacteria spp. much more efficiently.", "contents": "Myeloperoxidase-Cl--H2O2 bactericidal system: effect of bacterial membrane structure and growth conditions. The human-myeloperoxidase-Cl--H2O2 bactericidal system killed (i) smooth Enterobacteria spp. greater than or equal to rough and (ii) static-grown, stationary-phase bacteria greater than or equal to aerated-grown, log-phase. This is in contrast to human neutrophil granule extracts (involved in nonoxidative bactericidal mechanisms) that kill rough and aerated log-phase Enterobacteria spp. much more efficiently."}
{"id": "PMID:205506", "title": "Intestinal enzyme activities in germfree, conventional, and gnotobiotic rats associated with indigenous microorganisms.", "content": "Various enzyme activities involved in the active transport system, glycolysis, and digestion were assayed in various parts of the gastrointestinal tracts of germfree, conventional, and gnotobiotic rats associated with indigenous bacteria. The activity levels of alkaline phosphatase, glucose 6-phosphatase, adenosine triphosphatase, and disaccharidases in the upper small intestine were highest in all parts of the gastrointestinal tracts of various kinds of gnotobiotic, conventional, and germfree rats. Alkaline phosphatase, glucose 6-phosphatase, and adenosine triphosphatase activities in the upper small intestine of germfree rats were, respectively, 2.3-, 2.9-, and 1.7-fold higher than those in conventional rats. Similar to the results of these enzymes, sucrase, maltase, trehalase, and lactase activities in the upper small intestine of germfree rats were, respectively, 1.6-, 1.5-, 2.3-, and 1.8-fold higher than those in conventional rats. In various gnotobiotic rats, enzyme activity levels were intermediate between those in germfree and conventional rats. These findings suggest that those enzymatic activities are strongly depressed by the association with the indigenous microorganisms in the epithelial mucosa of the upper small intestine of rats. The levels of pyruvate kinase, hexokinase, and lactate dehydrogenase activities were highest, respectively, in the stomach, cecum, and the upper small intestine and cecum in all parts of the gastrointestinal tracts in various kinds of gnotobiotic, conventional, and germfree rats. It was also shown that six kinds of gastrointestinal bacteria, including lactobacilli, significantly depressed the enzyme activity levels to levels between those of the germfree and conventional rats in the upper small intestine of gnotobiotic rats.", "contents": "Intestinal enzyme activities in germfree, conventional, and gnotobiotic rats associated with indigenous microorganisms. Various enzyme activities involved in the active transport system, glycolysis, and digestion were assayed in various parts of the gastrointestinal tracts of germfree, conventional, and gnotobiotic rats associated with indigenous bacteria. The activity levels of alkaline phosphatase, glucose 6-phosphatase, adenosine triphosphatase, and disaccharidases in the upper small intestine were highest in all parts of the gastrointestinal tracts of various kinds of gnotobiotic, conventional, and germfree rats. Alkaline phosphatase, glucose 6-phosphatase, and adenosine triphosphatase activities in the upper small intestine of germfree rats were, respectively, 2.3-, 2.9-, and 1.7-fold higher than those in conventional rats. Similar to the results of these enzymes, sucrase, maltase, trehalase, and lactase activities in the upper small intestine of germfree rats were, respectively, 1.6-, 1.5-, 2.3-, and 1.8-fold higher than those in conventional rats. In various gnotobiotic rats, enzyme activity levels were intermediate between those in germfree and conventional rats. These findings suggest that those enzymatic activities are strongly depressed by the association with the indigenous microorganisms in the epithelial mucosa of the upper small intestine of rats. The levels of pyruvate kinase, hexokinase, and lactate dehydrogenase activities were highest, respectively, in the stomach, cecum, and the upper small intestine and cecum in all parts of the gastrointestinal tracts in various kinds of gnotobiotic, conventional, and germfree rats. It was also shown that six kinds of gastrointestinal bacteria, including lactobacilli, significantly depressed the enzyme activity levels to levels between those of the germfree and conventional rats in the upper small intestine of gnotobiotic rats."}
{"id": "PMID:205507", "title": "Role of activated macrophages in resistance of congenitally athymic nude mice to hepatitis induced by herpes simplex virus type 2.", "content": "Congenitally athymic nude (nu/nu) mice of a BALB/c genetic background were found considerably more resistant to the induction of focal necrotic hepatitis by herpes simplex virus type 2 (HSV-2) tha, were phenotypically normal littermates (nu/+) or BALB/c mice. The augmented resistance was age dependent, as it was only manifested in mice from 4 to 5 weeks of age. Studies of the course of infection showed that nude mice were able to restrain virus multiplication in the liver far better than normal mice in the early phase of infection. However, they seemed inferior to normal mice in eliminating the infectious process. In vitro investigation of peritoneal macrophages revealed that macrophages from 6-week-old nude mice exhibited accelerated spreading and were three times as restrictive in the replication of HSV-2 as macrophages from normal mice. However, no difference was found in the efficiency of adsorption/phagocytosis between  macrophages from nude and normal mice. The increased resistance of nude mice could be abolished by blockade of the microphage function of the mice by silica. Nude mice reconstituted at birth with thymus cells were just as susceptible to infection as normal mice. These data suggest that the increased resistance of nude mice to HSV-2 hepatitis is due to the presence of nonspecifically activated macrophages before infection.", "contents": "Role of activated macrophages in resistance of congenitally athymic nude mice to hepatitis induced by herpes simplex virus type 2. Congenitally athymic nude (nu/nu) mice of a BALB/c genetic background were found considerably more resistant to the induction of focal necrotic hepatitis by herpes simplex virus type 2 (HSV-2) tha, were phenotypically normal littermates (nu/+) or BALB/c mice. The augmented resistance was age dependent, as it was only manifested in mice from 4 to 5 weeks of age. Studies of the course of infection showed that nude mice were able to restrain virus multiplication in the liver far better than normal mice in the early phase of infection. However, they seemed inferior to normal mice in eliminating the infectious process. In vitro investigation of peritoneal macrophages revealed that macrophages from 6-week-old nude mice exhibited accelerated spreading and were three times as restrictive in the replication of HSV-2 as macrophages from normal mice. However, no difference was found in the efficiency of adsorption/phagocytosis between  macrophages from nude and normal mice. The increased resistance of nude mice could be abolished by blockade of the microphage function of the mice by silica. Nude mice reconstituted at birth with thymus cells were just as susceptible to infection as normal mice. These data suggest that the increased resistance of nude mice to HSV-2 hepatitis is due to the presence of nonspecifically activated macrophages before infection."}
{"id": "PMID:205508", "title": "Enhanced resistance against Junin virus infection induced by Corynebacterium parvum.", "content": "The effects of intraperitoneal administration of Corynebacterium parvum on the course of Junin virus infection in mice were investigated. This treatment produced enhanced resistance to the virus infection, evidenced by an increase in both survival times and the proportion of survivors. The protective effect was dependent upon the dose of C. parvum, and 280 mug/g of body weight was found to be the optimal dose. In various experiments, about 80% of the infected animals receiving this dose survived, whereas survival ranged between 0 and 20% among untreated infected mice. Maximal protection was afforded by C. parvum when administered simultaneously with the virus. A smaller but significant degree of resistance was induced by C. parvum given 3 or 6 days after infection. C. parvum injected before infection was ineffective. Viral titers measured in the brains of C. parvum-treated and untreated mice at various times after infection were found to be comparable. In addition, there were no significant differences between circulating-antibody titers measured either by neutralization tests or by complement fixation. Depression of the reticuloendothelial system by treatment with silica particles also resulted in enhanced resistance to Junin virus infection, suggesting that the protective effect of C. parvum is not likely to be due merely to its capacity to stimulate macrophages. The present data, highlighting that the presence of high titers of Junin virus and disease do not necessarily correlated, suggest that in mice this disease is not the consequence of cell damage caused directly by the virus but of a still undefined indirect mechanism induced by the virus, not necessarily mediated by macrophages.", "contents": "Enhanced resistance against Junin virus infection induced by Corynebacterium parvum. The effects of intraperitoneal administration of Corynebacterium parvum on the course of Junin virus infection in mice were investigated. This treatment produced enhanced resistance to the virus infection, evidenced by an increase in both survival times and the proportion of survivors. The protective effect was dependent upon the dose of C. parvum, and 280 mug/g of body weight was found to be the optimal dose. In various experiments, about 80% of the infected animals receiving this dose survived, whereas survival ranged between 0 and 20% among untreated infected mice. Maximal protection was afforded by C. parvum when administered simultaneously with the virus. A smaller but significant degree of resistance was induced by C. parvum given 3 or 6 days after infection. C. parvum injected before infection was ineffective. Viral titers measured in the brains of C. parvum-treated and untreated mice at various times after infection were found to be comparable. In addition, there were no significant differences between circulating-antibody titers measured either by neutralization tests or by complement fixation. Depression of the reticuloendothelial system by treatment with silica particles also resulted in enhanced resistance to Junin virus infection, suggesting that the protective effect of C. parvum is not likely to be due merely to its capacity to stimulate macrophages. The present data, highlighting that the presence of high titers of Junin virus and disease do not necessarily correlated, suggest that in mice this disease is not the consequence of cell damage caused directly by the virus but of a still undefined indirect mechanism induced by the virus, not necessarily mediated by macrophages."}
{"id": "PMID:205509", "title": "Production of interferon and serum hyporeactivity factor in mice infected with murine cytomegalovirus.", "content": "Mice injected intraperitoneally with murine cytomegalovirus produced as many as 1,000 U of serum interferon. The response appeared biphasic, with maximum titers in the first phase detectable from 2 through 4 days after infection. A second phase peaked 10 days after infection. By carboxyhexyl-Sepharose affinity chromatography, the serum interferon behaved like lymphocyte interferon. The infected mice also produced substantial quantities of serum hyporeactivity factor (D.A. Stringfellow, E.R. Kern, D.K. Kelsey, and L.A. Glasgow, J. Infect. Dis. 135:540-551, 1977), although always in the presence of interferon. This factor was separated from the serum interferon by concanavalin A-Sepharose affinity chromatography.", "contents": "Production of interferon and serum hyporeactivity factor in mice infected with murine cytomegalovirus. Mice injected intraperitoneally with murine cytomegalovirus produced as many as 1,000 U of serum interferon. The response appeared biphasic, with maximum titers in the first phase detectable from 2 through 4 days after infection. A second phase peaked 10 days after infection. By carboxyhexyl-Sepharose affinity chromatography, the serum interferon behaved like lymphocyte interferon. The infected mice also produced substantial quantities of serum hyporeactivity factor (D.A. Stringfellow, E.R. Kern, D.K. Kelsey, and L.A. Glasgow, J. Infect. Dis. 135:540-551, 1977), although always in the presence of interferon. This factor was separated from the serum interferon by concanavalin A-Sepharose affinity chromatography."}
{"id": "PMID:205510", "title": "Heterophil antigen in bovine sera detectable by immune adherence hemagglutination with infectious mononucleosis sera.", "content": "Bovine sera for tissue culture use were shown to contain heterophil antigen of the Paul-Bunnell-Davidsohn type by immune adherence hemagglutination tests with sera from patients with infectious mononucleosis. The antibody titers observed were comparable to those determined by two other methods; i.e., the immune adherence hemagglutination test was found to be as specific as the differential absorption test with horse erythrocytes or the ox cell hemolysis assay,but it appeared to be the most sensitive of the three procedures. All 16 individual or pooled bovine serum samples showed Paul-Bunnell-Davidsohn antigen at concentrations varying over a fourfold range. The potential usefulness of the immune adherence hemagglutination test for various Paul-Bunnell-Davidsohn antigen-related problems and implications of the observations are discussed.", "contents": "Heterophil antigen in bovine sera detectable by immune adherence hemagglutination with infectious mononucleosis sera. Bovine sera for tissue culture use were shown to contain heterophil antigen of the Paul-Bunnell-Davidsohn type by immune adherence hemagglutination tests with sera from patients with infectious mononucleosis. The antibody titers observed were comparable to those determined by two other methods; i.e., the immune adherence hemagglutination test was found to be as specific as the differential absorption test with horse erythrocytes or the ox cell hemolysis assay,but it appeared to be the most sensitive of the three procedures. All 16 individual or pooled bovine serum samples showed Paul-Bunnell-Davidsohn antigen at concentrations varying over a fourfold range. The potential usefulness of the immune adherence hemagglutination test for various Paul-Bunnell-Davidsohn antigen-related problems and implications of the observations are discussed."}
{"id": "PMID:205511", "title": "Oral--facial pain: old puzzles, new postulates.", "content": "Dental examples are given (e.g. referred pain, V neuralgia) which exemplify the multifactorial and puzzling nature of pain. Pain results from a noxious stimulus activating some of the small-diameter myelinated and unmyelinated afferent nerve fibres that innervate skin, mucosa, teeth etc. It is complex experience including the sensation experienced as well as the emotional, cognitive and motivational reactions evoked by the stimulus. Pain is not a simple function of the magnitude of damage caused by the stimulus, but also depends on factors such as the person's emotions, past experience of pain, and other concomitant sensory experiences (e.g. with acupuncture). Early postulates of pain failed to take all these factors into account. In the V system (Fig. 1), the specificity theory would maintain that there exists a 'private pain path' from oral-facial tissues to the cerebral cortex, with nerve fibres and brain cells in this path responsive only to stimulu of a noxious character (Fig. 2). But anatomical, physiological and psychological observations have failed to give full support to this theory and other postulates of pain. Although some details of the more recently proposed gate control theory have not been sustantiated, this theory has provided a good general framework for viewing pain and has stimulated much recent research. It emphasizes sensory interaction between large and small-diameter afferent nerve fibres in the gate control system, and regulation over central pain transmission through the gate by descending central controls (Fig. 3). In the V system, brain cells involved in central pain transmission have now been found (Fig. 4), and sensory interactions and descending controls on these brain cells noted (Fig. 5). Neural mechanisms such as these have been implicated in pain, and in its control by procedures such as acupuncture, suggestion, distraction and narcotic analgesia.", "contents": "Oral--facial pain: old puzzles, new postulates. Dental examples are given (e.g. referred pain, V neuralgia) which exemplify the multifactorial and puzzling nature of pain. Pain results from a noxious stimulus activating some of the small-diameter myelinated and unmyelinated afferent nerve fibres that innervate skin, mucosa, teeth etc. It is complex experience including the sensation experienced as well as the emotional, cognitive and motivational reactions evoked by the stimulus. Pain is not a simple function of the magnitude of damage caused by the stimulus, but also depends on factors such as the person's emotions, past experience of pain, and other concomitant sensory experiences (e.g. with acupuncture). Early postulates of pain failed to take all these factors into account. In the V system (Fig. 1), the specificity theory would maintain that there exists a 'private pain path' from oral-facial tissues to the cerebral cortex, with nerve fibres and brain cells in this path responsive only to stimulu of a noxious character (Fig. 2). But anatomical, physiological and psychological observations have failed to give full support to this theory and other postulates of pain. Although some details of the more recently proposed gate control theory have not been sustantiated, this theory has provided a good general framework for viewing pain and has stimulated much recent research. It emphasizes sensory interaction between large and small-diameter afferent nerve fibres in the gate control system, and regulation over central pain transmission through the gate by descending central controls (Fig. 3). In the V system, brain cells involved in central pain transmission have now been found (Fig. 4), and sensory interactions and descending controls on these brain cells noted (Fig. 5). Neural mechanisms such as these have been implicated in pain, and in its control by procedures such as acupuncture, suggestion, distraction and narcotic analgesia."}
{"id": "PMID:205512", "title": "Persistent and boosterable IgE antibody production in mice injected with low doses of ovalbumin and silica.", "content": "The results of the present experiments show that Aerosil, an amorphous submicroscopic silica, is able to stimulate in Swiss outbred mice the production of IgE antibodies to a single 1 microgram dose of Ovalbumin (OA) in experimental conditions in which detectable IgG1 antibodies were not produced. The production of IgE anti-OA antibodies stimulated by silica was persistent for a least 4 months, and demonstrated a secondary stimulation. Neither IgE nor IgG1 anti-OA antibodies were demonstrable when mice were immunized with OA alone or OA with aluminum hydroxide.", "contents": "Persistent and boosterable IgE antibody production in mice injected with low doses of ovalbumin and silica. The results of the present experiments show that Aerosil, an amorphous submicroscopic silica, is able to stimulate in Swiss outbred mice the production of IgE antibodies to a single 1 microgram dose of Ovalbumin (OA) in experimental conditions in which detectable IgG1 antibodies were not produced. The production of IgE anti-OA antibodies stimulated by silica was persistent for a least 4 months, and demonstrated a secondary stimulation. Neither IgE nor IgG1 anti-OA antibodies were demonstrable when mice were immunized with OA alone or OA with aluminum hydroxide."}
{"id": "PMID:205513", "title": "Coordination of institution and parole services: an innovation within California's Civil Addict Program.", "content": "Parole outcome was measured 1 year after release of 397 narcotic addicts processed by an experimental program in which both institution and parole services were administered together. Conparison of outcome of this group to the outcome of 361 traditionally processed addicts revealed a positive effect on parole outcome of violators (those with prior parole experience) compared to new commitments (p less than .05). This was particularly true for the community parole unit which made most use of community resources (p less than .05). Community adjustment of some narcotic addicts may be increased by administrative interdependence and by optimal use of other community resources. The future for such programs seems brightest at the local level of government.", "contents": "Coordination of institution and parole services: an innovation within California's Civil Addict Program. Parole outcome was measured 1 year after release of 397 narcotic addicts processed by an experimental program in which both institution and parole services were administered together. Conparison of outcome of this group to the outcome of 361 traditionally processed addicts revealed a positive effect on parole outcome of violators (those with prior parole experience) compared to new commitments (p less than .05). This was particularly true for the community parole unit which made most use of community resources (p less than .05). Community adjustment of some narcotic addicts may be increased by administrative interdependence and by optimal use of other community resources. The future for such programs seems brightest at the local level of government."}
{"id": "PMID:205514", "title": "E.s.r. of spin-trapped radicals in aqueous solutions of peptides. Reactions of the hydroxyl radical.", "content": "The reactions of hydroxyl radicals with 30 dipeptides and several larger peptides were studied in aqueous solutions. The OH radicals were generated by U.V. photolysis of H2O2. The short-lived peptide radicals were spin-trapped using t-nitrosobutane and identified by e.s.r. For dipeptides containing the amino terminal residues glycine, alanine and phenylalanine, abstraction of the hydrogen from the carbon adjacent to the peptide nitrogen was the major process leading to the spin-adducts. Such radicals will be referred to as backbone radicals. Dipeptides with a carbonyl terminal serine residue and also glycylglutamic acid form both backbone and side-chain radicals, with the latter being formed in larger quantities. For dipeptides, side-chain radicals were detected on either the carboxyl or amino terminal residues of both. The effect of pD on the e.s.r. sectrum of the spin-adducts of glycylglycine was studied and the pK of the carboxyl group of this radical was determined to be 2.5. For (Ala)3 and (Ala)n, with an average value of n = 1800, backbone and minor side-chain radicals were observed. For ribonucleases-S-peptide, containing 20 amino acid residues, both backbone and side-chain radicals were detected.", "contents": "E.s.r. of spin-trapped radicals in aqueous solutions of peptides. Reactions of the hydroxyl radical. The reactions of hydroxyl radicals with 30 dipeptides and several larger peptides were studied in aqueous solutions. The OH radicals were generated by U.V. photolysis of H2O2. The short-lived peptide radicals were spin-trapped using t-nitrosobutane and identified by e.s.r. For dipeptides containing the amino terminal residues glycine, alanine and phenylalanine, abstraction of the hydrogen from the carbon adjacent to the peptide nitrogen was the major process leading to the spin-adducts. Such radicals will be referred to as backbone radicals. Dipeptides with a carbonyl terminal serine residue and also glycylglutamic acid form both backbone and side-chain radicals, with the latter being formed in larger quantities. For dipeptides, side-chain radicals were detected on either the carboxyl or amino terminal residues of both. The effect of pD on the e.s.r. sectrum of the spin-adducts of glycylglycine was studied and the pK of the carboxyl group of this radical was determined to be 2.5. For (Ala)3 and (Ala)n, with an average value of n = 1800, backbone and minor side-chain radicals were observed. For ribonucleases-S-peptide, containing 20 amino acid residues, both backbone and side-chain radicals were detected."}
{"id": "PMID:205515", "title": "E.s.r. study of spin-trapped radicals formed during the photolysis of aqueous solutions of acid amides and H2O2.", "content": "Free radicals formed by the reactions of OH radicals with amides and their N-methylated derivatives in aqueous solutions have been studied. The OH radicals were produced by U.V.-photolysis of H2O2, and the short-lived amide radicals were converted to more stable nitroxide radicals by addition to a spin-trap, tert-nitrosobutane. The spin-trapped radicals were identified by e.s.r. spectroscopy. For acetamide, chloroacetamide, malonamide, succinamide and propionamide, the observed radicals were formed by H-abstraction from the carbon atoms attached to the carbonyl group. The H atom attached to the carbonyl group was abstracted in formamide. For N-methyl acetamide, N,N-dimethyl acetamide and the corresponding formamide derivatives, H-abstraction occurred only from the N-methyl group. The non-equivalency of the amide protons was observed in the spin-trapped radicals for acetamide, formamide, malonamide, succinamide and propionamide. The identification of the site of OH attack on N-methyl amides is helpful for the study of radical formation in peptides and proteins.", "contents": "E.s.r. study of spin-trapped radicals formed during the photolysis of aqueous solutions of acid amides and H2O2. Free radicals formed by the reactions of OH radicals with amides and their N-methylated derivatives in aqueous solutions have been studied. The OH radicals were produced by U.V.-photolysis of H2O2, and the short-lived amide radicals were converted to more stable nitroxide radicals by addition to a spin-trap, tert-nitrosobutane. The spin-trapped radicals were identified by e.s.r. spectroscopy. For acetamide, chloroacetamide, malonamide, succinamide and propionamide, the observed radicals were formed by H-abstraction from the carbon atoms attached to the carbonyl group. The H atom attached to the carbonyl group was abstracted in formamide. For N-methyl acetamide, N,N-dimethyl acetamide and the corresponding formamide derivatives, H-abstraction occurred only from the N-methyl group. The non-equivalency of the amide protons was observed in the spin-trapped radicals for acetamide, formamide, malonamide, succinamide and propionamide. The identification of the site of OH attack on N-methyl amides is helpful for the study of radical formation in peptides and proteins."}
{"id": "PMID:205516", "title": "Modification of rat thymocyte membrane properties by hyperthermia and ionizing radiation.", "content": "Thymocytes are one the most widely used cell models for the study of radiation-induced interphase death. This cell-type was chosen for the study of hyperthermic and radiation effects on two membrane-related processes implicated in the interphase death of cells: Na+-dependent 2-aminoisobutyric acid (AIB) transport and cyclic 3'-5' adenosine monophsophate formation. The response of AIB transport to heat is dose-dependent, but the biphasic thermal response curve (AIB uptake versus time) differs fom the sigmoidal radiation response curve. Heating thymocytes for 20-30 min at 43 degrees C stimulates AIB uptake. Additional heating at 43 degrees C, however, markedly reduces AIB uptake. Despite the immediate stimulating effect of heat (30 min at 43 degrees C), the thymocyte has already developed irrepairable impairments, as demonstrated by the fractionated heating experiments. The heat-induced impairment of AIB uptake is mainly on the Na+-dependent component of neutral amino-acid transport, affecting primarily the maximal rate of uptake, i.e. Vmax. Additional evidence for heat-induced plasma membrane damage is the alteration in cAMP levels. Heating thymocytes for 30 min or longer at 43 degrees C causes a massive rise in cAMP level within the cell. This differs from thymocytes exposed to radiation where no rise in cAMP is observed.", "contents": "Modification of rat thymocyte membrane properties by hyperthermia and ionizing radiation. Thymocytes are one the most widely used cell models for the study of radiation-induced interphase death. This cell-type was chosen for the study of hyperthermic and radiation effects on two membrane-related processes implicated in the interphase death of cells: Na+-dependent 2-aminoisobutyric acid (AIB) transport and cyclic 3'-5' adenosine monophsophate formation. The response of AIB transport to heat is dose-dependent, but the biphasic thermal response curve (AIB uptake versus time) differs fom the sigmoidal radiation response curve. Heating thymocytes for 20-30 min at 43 degrees C stimulates AIB uptake. Additional heating at 43 degrees C, however, markedly reduces AIB uptake. Despite the immediate stimulating effect of heat (30 min at 43 degrees C), the thymocyte has already developed irrepairable impairments, as demonstrated by the fractionated heating experiments. The heat-induced impairment of AIB uptake is mainly on the Na+-dependent component of neutral amino-acid transport, affecting primarily the maximal rate of uptake, i.e. Vmax. Additional evidence for heat-induced plasma membrane damage is the alteration in cAMP levels. Heating thymocytes for 30 min or longer at 43 degrees C causes a massive rise in cAMP level within the cell. This differs from thymocytes exposed to radiation where no rise in cAMP is observed."}
{"id": "PMID:205520", "title": "The effect of prednisolone on antibody-dependent cell-mediated cytotoxicity and the growth of type I herpes simplex virus in human cells.", "content": "Treatment of human skin and corneal fibroblasts with prednisolone-21-phosphate did not increase the capacity of these cells to replicate type I herpes simplex virus (HSV). The steroid however was found to (1) inhibit human lymphocytes from mediating antibody-dependent cell-mediated cytotoxicity (ADCC) against HSV-infected fibroblasts and (2) suppress the replication of virus in PHA-stimulated human lymphocytes. The data suggest that the exacerbation observed when patients with dendritic keratitis are inadvertently treated with prednisolone may be due to the steroid suppressing ADCC and not by promoting the growth of virus in the corneal cells.", "contents": "The effect of prednisolone on antibody-dependent cell-mediated cytotoxicity and the growth of type I herpes simplex virus in human cells. Treatment of human skin and corneal fibroblasts with prednisolone-21-phosphate did not increase the capacity of these cells to replicate type I herpes simplex virus (HSV). The steroid however was found to (1) inhibit human lymphocytes from mediating antibody-dependent cell-mediated cytotoxicity (ADCC) against HSV-infected fibroblasts and (2) suppress the replication of virus in PHA-stimulated human lymphocytes. The data suggest that the exacerbation observed when patients with dendritic keratitis are inadvertently treated with prednisolone may be due to the steroid suppressing ADCC and not by promoting the growth of virus in the corneal cells."}
{"id": "PMID:205521", "title": "Histochemical demonstration of cyclic guanosine 3',5'-monophosphate phosphodiesterase activity in retinal photoreceptor outer segments.", "content": "A technique for the histochemical demonstration of cyclic guanosine monophosphate phosphodiesterase in retina is described. Enzyme activity was identified on photoreceptor outer segment lamellae, a finding in agreement with previous biochemical data on isolated outer segment preparations. The distribution of phosphodiesterase activity for cyclic guanosine monophosphate was similar to that found previously in rod outer segments for cyclic adenosine monophosphate, suggesting that the same enzyme may hydrolyze both nucleotides.", "contents": "Histochemical demonstration of cyclic guanosine 3',5'-monophosphate phosphodiesterase activity in retinal photoreceptor outer segments. A technique for the histochemical demonstration of cyclic guanosine monophosphate phosphodiesterase in retina is described. Enzyme activity was identified on photoreceptor outer segment lamellae, a finding in agreement with previous biochemical data on isolated outer segment preparations. The distribution of phosphodiesterase activity for cyclic guanosine monophosphate was similar to that found previously in rod outer segments for cyclic adenosine monophosphate, suggesting that the same enzyme may hydrolyze both nucleotides."}
{"id": "PMID:205522", "title": "Involvement of the sympathetic nervous system in the urinary bladder internal sphincter and in penile erection in the anesthetized cat.", "content": "Male cats were anesthetized with pentobarbital. In one series of experiments a Foley catheter was placed suprapubically in the urinary bladder and physiologic saline, under a constant head of pressure, was allowed to flow at a constant rate through the bladder. Alpha-adrenergic stimulants such as ephedrine, norepinephrine, or methoxamine all caused a decrease or cessation in urinary flow. This effect was reversed by the alpha-adrenergic blocking agent, phentolamine. In addition, phentolamine administration caused penile erection. Erection also occurred after administration of the alpha-adrenergic blocking agent, phenoxybenzamine, or the beta2-adrenergic stimulants terbutaline or salbutamol. In each case the erection could be reversed, and usually terminated completely, by administration of the beta-adrenergic blocking agent, propranolol. Hypotension per se was not the required event to initiate erection because administration of acetylcholine, histamine, or prostaglandin E2 did not result in penile erection. In two of five experiments nitroprusside caused an erection. It was concluded that a predominance of beta2 activity in the penile vasculature is involved in erection.", "contents": "Involvement of the sympathetic nervous system in the urinary bladder internal sphincter and in penile erection in the anesthetized cat. Male cats were anesthetized with pentobarbital. In one series of experiments a Foley catheter was placed suprapubically in the urinary bladder and physiologic saline, under a constant head of pressure, was allowed to flow at a constant rate through the bladder. Alpha-adrenergic stimulants such as ephedrine, norepinephrine, or methoxamine all caused a decrease or cessation in urinary flow. This effect was reversed by the alpha-adrenergic blocking agent, phentolamine. In addition, phentolamine administration caused penile erection. Erection also occurred after administration of the alpha-adrenergic blocking agent, phenoxybenzamine, or the beta2-adrenergic stimulants terbutaline or salbutamol. In each case the erection could be reversed, and usually terminated completely, by administration of the beta-adrenergic blocking agent, propranolol. Hypotension per se was not the required event to initiate erection because administration of acetylcholine, histamine, or prostaglandin E2 did not result in penile erection. In two of five experiments nitroprusside caused an erection. It was concluded that a predominance of beta2 activity in the penile vasculature is involved in erection."}
{"id": "PMID:205523", "title": "Angiotensin-converting enzyme in macrophages and Freund's adjuvant granuloma.", "content": "Low angiotensin-converting enzyme (ACE) activity was found in rat and mouse peritoneal macrophages, in rat and rabbit pulmonary alveolar macrophages, in cultured mouse peritoneal macrophages stimulated i.p. for four days by thioglycollate, and in rabbit pulmonary alveolar macrophages stimulated in culture by 0.1 to 100 microgram/ml Salmonella typhosa endotoxin for four days. Rat subcutaneous Freund's adjuvant granulomas induced with Mycobacterium butyricum or M. tuberculosis H37 Ra contianed low ACE activity which was generally lower than that present in control tissues. Increased ACE activity in sarcoidosis and Gaucher's disease lesions does not reflect a universally high synthesis of ACE in mammalian macrophages or granulomas, but may be due to specific mechanisms.", "contents": "Angiotensin-converting enzyme in macrophages and Freund's adjuvant granuloma. Low angiotensin-converting enzyme (ACE) activity was found in rat and mouse peritoneal macrophages, in rat and rabbit pulmonary alveolar macrophages, in cultured mouse peritoneal macrophages stimulated i.p. for four days by thioglycollate, and in rabbit pulmonary alveolar macrophages stimulated in culture by 0.1 to 100 microgram/ml Salmonella typhosa endotoxin for four days. Rat subcutaneous Freund's adjuvant granulomas induced with Mycobacterium butyricum or M. tuberculosis H37 Ra contianed low ACE activity which was generally lower than that present in control tissues. Increased ACE activity in sarcoidosis and Gaucher's disease lesions does not reflect a universally high synthesis of ACE in mammalian macrophages or granulomas, but may be due to specific mechanisms."}
{"id": "PMID:205525", "title": "Distribution of ACTH-like immunoreactivity in rat brain and gastrointestinal tract.", "content": "Immunocytochemistry reveals ACTH-like immunoreactivity to reside not only in the pituitary but also in central nerves and in central nerves and in antral gastrin cells. In all probability, the central nerves store a peptide identical with or closely resembling true ACTH. Their pattern of distribution is, in some regions, similar to that of enkephalin-immunoreactive nerves. The antiserum demonstrating ACTH-like immunoreactivity in central nerves and in antral gastrin cells is directed towards the COOH-terminal part of the hormone. A peptide corresponding to this part, the corticotrophin-like intermediate peptide (CLIP) is manufactured by the pars intermedia of the pituitary. CLIP is devoid of adrenocortical activity, but has recently been shown to possess insulin-releasing activity. The occurrence of CLIP-like peptides in antral gastrin cells may indicate a role for such peptides in the gastrointestinal regulation of insulin release. The simultaneous occurrence of enkephalin-like and ACTH-like immunoreactivity in the antral gastrin cells is of particular interest since a large precursor molecule, containing both the enkephalin and the ACTH sequence has recently been identified.", "contents": "Distribution of ACTH-like immunoreactivity in rat brain and gastrointestinal tract. Immunocytochemistry reveals ACTH-like immunoreactivity to reside not only in the pituitary but also in central nerves and in central nerves and in antral gastrin cells. In all probability, the central nerves store a peptide identical with or closely resembling true ACTH. Their pattern of distribution is, in some regions, similar to that of enkephalin-immunoreactive nerves. The antiserum demonstrating ACTH-like immunoreactivity in central nerves and in antral gastrin cells is directed towards the COOH-terminal part of the hormone. A peptide corresponding to this part, the corticotrophin-like intermediate peptide (CLIP) is manufactured by the pars intermedia of the pituitary. CLIP is devoid of adrenocortical activity, but has recently been shown to possess insulin-releasing activity. The occurrence of CLIP-like peptides in antral gastrin cells may indicate a role for such peptides in the gastrointestinal regulation of insulin release. The simultaneous occurrence of enkephalin-like and ACTH-like immunoreactivity in the antral gastrin cells is of particular interest since a large precursor molecule, containing both the enkephalin and the ACTH sequence has recently been identified."}
{"id": "PMID:205527", "title": "Ventilatory and waking responses to hypoxia in sleeping dogs.", "content": "We examined  waking and ventilatory responses to acute hypoxia in four dogs during natural sleep. Progressive hypoxia was induced by a rebreathing technique in which alveolar CO2 pressure (PACO2) was held at the eucapnic level. Arterial O2 saturation (SaO2) was measured with an ear oximeter, and sleep stage was determined by electroencephalographic and behavioral criteria. Arousal from eucapnic hypoxia occurred at a SaO2 of 87.5 +/- 2.6% (mean +/- SE) during slow-wave sleep (SWS), and at a SaO2 of 70.5 +/- 3.4% during rapid-eye-movement (REM) sleep (P less than 0.005). The irregular pattern of breathing typical of REM sleep persisted during hypoxia. However linear regression analysis of breath-by-breath instantaneous minute volume of ventilation (VI) against SaO2 revealed regression coefficients in REM sleep that were similar to those found in SWS and wakefulness. This finding contrasts with earlier observations of a decreased response of VI to CO2 during REM sleep. The results indicate that although waking responses to hypoxia are delayed in REM sleep, ventilatory responses remain intact and therefore may be of importance in maintaining adequate ventilation during this stage of sleep.", "contents": "Ventilatory and waking responses to hypoxia in sleeping dogs. We examined  waking and ventilatory responses to acute hypoxia in four dogs during natural sleep. Progressive hypoxia was induced by a rebreathing technique in which alveolar CO2 pressure (PACO2) was held at the eucapnic level. Arterial O2 saturation (SaO2) was measured with an ear oximeter, and sleep stage was determined by electroencephalographic and behavioral criteria. Arousal from eucapnic hypoxia occurred at a SaO2 of 87.5 +/- 2.6% (mean +/- SE) during slow-wave sleep (SWS), and at a SaO2 of 70.5 +/- 3.4% during rapid-eye-movement (REM) sleep (P less than 0.005). The irregular pattern of breathing typical of REM sleep persisted during hypoxia. However linear regression analysis of breath-by-breath instantaneous minute volume of ventilation (VI) against SaO2 revealed regression coefficients in REM sleep that were similar to those found in SWS and wakefulness. This finding contrasts with earlier observations of a decreased response of VI to CO2 during REM sleep. The results indicate that although waking responses to hypoxia are delayed in REM sleep, ventilatory responses remain intact and therefore may be of importance in maintaining adequate ventilation during this stage of sleep."}
{"id": "PMID:205528", "title": "Physical activity and hypophysectomy on the aerobic capacity of ligaments and tendons.", "content": "Traditionally, ligaments and tendons (L and T) have been regarded as metabolically inert structures. However, sufficient biochemical evidence on the metabolism of collagen has indicated that such a concept is no longer tenable. To determine whether L and T respond to increased or decreased levels of chronic exercise, studies were undertaken to measure their aerobic capacities. For comparative purposes, similar measurements were obtained from liver and skeletal muscles secured from normal and hypophysectomized male rats. Oxygen consumption and cytochrome oxidase (CO) activity was recorded from cell suspensions that had been prepared with the inclusion of collagenase and with elastase added to the medium. The O2 results showed that L and T had values that were approximately 10 times lower than liver tissue and 7.5 times less than the means from skeletal muscles. Hypophysectomy caused marked reductions in O2 uptake of liver and muscle tissues; but had no impact on L and T. When CO activity of these connective tissues were evaluated, immobilization and hypophysectomy caused significant reductions that ranged from -36% to -59% respectively. Training, on the other hand, resulted in increases of less than 10% in the activity of this enzyme within L and T while being elevated in muscle tissue by 58%. It was concluded that the metabolic activity of L and T was lowered with decreased levels of physical activity but it was unclear why chronic exercise did not produce the opposite effect.", "contents": "Physical activity and hypophysectomy on the aerobic capacity of ligaments and tendons. Traditionally, ligaments and tendons (L and T) have been regarded as metabolically inert structures. However, sufficient biochemical evidence on the metabolism of collagen has indicated that such a concept is no longer tenable. To determine whether L and T respond to increased or decreased levels of chronic exercise, studies were undertaken to measure their aerobic capacities. For comparative purposes, similar measurements were obtained from liver and skeletal muscles secured from normal and hypophysectomized male rats. Oxygen consumption and cytochrome oxidase (CO) activity was recorded from cell suspensions that had been prepared with the inclusion of collagenase and with elastase added to the medium. The O2 results showed that L and T had values that were approximately 10 times lower than liver tissue and 7.5 times less than the means from skeletal muscles. Hypophysectomy caused marked reductions in O2 uptake of liver and muscle tissues; but had no impact on L and T. When CO activity of these connective tissues were evaluated, immobilization and hypophysectomy caused significant reductions that ranged from -36% to -59% respectively. Training, on the other hand, resulted in increases of less than 10% in the activity of this enzyme within L and T while being elevated in muscle tissue by 58%. It was concluded that the metabolic activity of L and T was lowered with decreased levels of physical activity but it was unclear why chronic exercise did not produce the opposite effect."}
{"id": "PMID:205529", "title": "Epizootic of concurrent cutaneous streptococcal abscesses and swinepox in a herd of swine.", "content": "Concurrent cutaneous abscesses and swinepox were observed in a herd of swine. An ungroupable hemolytic streptococcus was isolated from the abscesses. Tests indicated that streptococci isolated from different swine were similar if not identical. Swinepox lesions were observed on swine only after weaning. Lice (Haematopinus suis) were numerous on the suckling and weaned swine and appeared to be resistant to lindane. Abscesses, swinepox, and lice were eliminated after the swine were treated with an organic phosphate insecticide and antibacterial agents were added to the rations.", "contents": "Epizootic of concurrent cutaneous streptococcal abscesses and swinepox in a herd of swine. Concurrent cutaneous abscesses and swinepox were observed in a herd of swine. An ungroupable hemolytic streptococcus was isolated from the abscesses. Tests indicated that streptococci isolated from different swine were similar if not identical. Swinepox lesions were observed on swine only after weaning. Lice (Haematopinus suis) were numerous on the suckling and weaned swine and appeared to be resistant to lindane. Abscesses, swinepox, and lice were eliminated after the swine were treated with an organic phosphate insecticide and antibacterial agents were added to the rations."}
{"id": "PMID:205530", "title": "Evidence from auditory nerve and brainstem evoked responses for an organic brain lesion in children with autistic traits.", "content": "In an attempt to resolve the question as to whether children with autistic traits have an organic nervous system lesion, auditory nerve and brainstem evoked responses were recorded in a group of 15 children with autistic traits. The most obvious results included a longer response latency of the auditory nerve and a longer brainstem transmission time, compared to normal children. Five of the autistic children were found to be profoundly deaf. These results strengthen the theory that an organic lesion of the nervous system can give rise to autistic traits.", "contents": "Evidence from auditory nerve and brainstem evoked responses for an organic brain lesion in children with autistic traits. In an attempt to resolve the question as to whether children with autistic traits have an organic nervous system lesion, auditory nerve and brainstem evoked responses were recorded in a group of 15 children with autistic traits. The most obvious results included a longer response latency of the auditory nerve and a longer brainstem transmission time, compared to normal children. Five of the autistic children were found to be profoundly deaf. These results strengthen the theory that an organic lesion of the nervous system can give rise to autistic traits."}
{"id": "PMID:205531", "title": "Autistic symptoms in a child with congenital cytomegalovirus infection.", "content": "A case of intrauterine cytomegalovirus infection with onset of autistic symptoms apparently after 6 months of age is reported. Physicians who find autistic symptoms in very young children might include cytomegalovirus in their differential to document the presence or absence of a correlation.", "contents": "Autistic symptoms in a child with congenital cytomegalovirus infection. A case of intrauterine cytomegalovirus infection with onset of autistic symptoms apparently after 6 months of age is reported. Physicians who find autistic symptoms in very young children might include cytomegalovirus in their differential to document the presence or absence of a correlation."}
{"id": "PMID:205533", "title": "Changes in cyclic AMP levels during development in Myxococcus xanthus.", "content": "Cyclic AMP levels doubled in Myxococcus xanthus under conditions in which cells aggregate and form fruiting bodies. In liquid medium, glycerol- or dimethyl sulfoxide-induced sporulating cultures exhibited a sharp but transient rise in cyclic AMP concentration after 45 min.", "contents": "Changes in cyclic AMP levels during development in Myxococcus xanthus. Cyclic AMP levels doubled in Myxococcus xanthus under conditions in which cells aggregate and form fruiting bodies. In liquid medium, glycerol- or dimethyl sulfoxide-induced sporulating cultures exhibited a sharp but transient rise in cyclic AMP concentration after 45 min."}
{"id": "PMID:205532", "title": "Arginine metabolism in Saccharomyces cerevisiae: subcellular localization of the enzymes.", "content": "Subcellular localization of enzymes of arginine metabolism in Saccharomyces cerevisiae was studied by partial fractionation and stepwise homogenization of spheroplast lysates. These enzymes could clearly be divided into two groups. The first group comprised the five enzymes of the acetylated compound cycle, i.e., acetylglutamate synthase, acetylglutamate kinase, acetylglutamyl-phosphate reductase, acetylornithine aminotransferase, and acetylornithine-glutamate acetyltransferase. These enzymes were exclusively particulate. Comparison with citrate synthase and cytochrome oxidase, and results from isopycnic gradient analysis, suggested that these enzymes were associated with the mitochondria. By contrast, enzymatic activities going from ornithine to arginine, i.e., arginine pathway-specific carbamoylphosphate synthetase, ornithine carbamoyltransferase, argininosuccinate synthetase, and argininosuccinate lyase, and the two first catabolic enzymes, arginase and ornithine aminotransferase, were in the \"soluble\" fraction of the cell.", "contents": "Arginine metabolism in Saccharomyces cerevisiae: subcellular localization of the enzymes. Subcellular localization of enzymes of arginine metabolism in Saccharomyces cerevisiae was studied by partial fractionation and stepwise homogenization of spheroplast lysates. These enzymes could clearly be divided into two groups. The first group comprised the five enzymes of the acetylated compound cycle, i.e., acetylglutamate synthase, acetylglutamate kinase, acetylglutamyl-phosphate reductase, acetylornithine aminotransferase, and acetylornithine-glutamate acetyltransferase. These enzymes were exclusively particulate. Comparison with citrate synthase and cytochrome oxidase, and results from isopycnic gradient analysis, suggested that these enzymes were associated with the mitochondria. By contrast, enzymatic activities going from ornithine to arginine, i.e., arginine pathway-specific carbamoylphosphate synthetase, ornithine carbamoyltransferase, argininosuccinate synthetase, and argininosuccinate lyase, and the two first catabolic enzymes, arginase and ornithine aminotransferase, were in the \"soluble\" fraction of the cell."}
{"id": "PMID:205534", "title": "Dimeric nature of apo-low density lipoprotein extracted with Triton X-100.", "content": "Human low density lipoprotein (LDL) was dissolved in 0.3 to 2.0% Triton X-100 at pH 7.5 and apo-LDL (B protein) was extracted from LDL to form B protein-Triton complex. Sedimentation equilibrium study of this complex in a solvent nearly isopycnic to Triton X-100 showed that the molecular weight of the protein in the complex was 570,000. The complex eluted almost at the void volume of a Sepharose 6B column, as would be expected for a complex with a total molecular weight of roughly 900,000, on the assumption that 0.52 g of Triton was bound to 1 g of protein (Helenius, A. and Simons, K. (1972) J. Biol. Chem. 247, 3656-3661). The sedimentation coefficient of the complex gave f/fmin = 2.2, indicating that the complex was either as asymmetric as a fibrinogen molecule or not compact. These results show that B protein exists in its complex with Triton X-100 as an elongated or a loosely expanded dimer based on the molecular weight of monomeric B protein of 270,000. B protein may also exist in LDL as a dimer.", "contents": "Dimeric nature of apo-low density lipoprotein extracted with Triton X-100. Human low density lipoprotein (LDL) was dissolved in 0.3 to 2.0% Triton X-100 at pH 7.5 and apo-LDL (B protein) was extracted from LDL to form B protein-Triton complex. Sedimentation equilibrium study of this complex in a solvent nearly isopycnic to Triton X-100 showed that the molecular weight of the protein in the complex was 570,000. The complex eluted almost at the void volume of a Sepharose 6B column, as would be expected for a complex with a total molecular weight of roughly 900,000, on the assumption that 0.52 g of Triton was bound to 1 g of protein (Helenius, A. and Simons, K. (1972) J. Biol. Chem. 247, 3656-3661). The sedimentation coefficient of the complex gave f/fmin = 2.2, indicating that the complex was either as asymmetric as a fibrinogen molecule or not compact. These results show that B protein exists in its complex with Triton X-100 as an elongated or a loosely expanded dimer based on the molecular weight of monomeric B protein of 270,000. B protein may also exist in LDL as a dimer."}
{"id": "PMID:205535", "title": "Characterization of electron transport enzymes in the envelope of rat liver nuclei.", "content": "Nuclei and microsomes were prepared from the livers of normal, phenobarbital (PB)-treated and beta-naphthoflavone (beta-NF)-treated rats, and the contents of several enzymes in both subcellular fractions were examined. In normal rats, the enzyme activities in the nuclear fraction were about one-third of those of microsomes on a phospholipid basis. The induction of some particular enzymes by the drugs was observed with nuclei as well as with microsomes. Cytochrome P-450 and NADPH-cytochrome c reductase were increased by PB treatment and cytochrome P-448 was induced by beta-NF treatment both in nuclei and in microsomes. The extents of inhibition of nuclear enzyme activities by the antibodies against corresponding microsomal enzymes were almost the same as those of the microsomal activities. It was concluded that a microsomal type electron transport system exists in rat liver nuclei, and that nuclear drug-oxidizing activities are inducible by PB or beta-NF as their microsomal counterparts are.", "contents": "Characterization of electron transport enzymes in the envelope of rat liver nuclei. Nuclei and microsomes were prepared from the livers of normal, phenobarbital (PB)-treated and beta-naphthoflavone (beta-NF)-treated rats, and the contents of several enzymes in both subcellular fractions were examined. In normal rats, the enzyme activities in the nuclear fraction were about one-third of those of microsomes on a phospholipid basis. The induction of some particular enzymes by the drugs was observed with nuclei as well as with microsomes. Cytochrome P-450 and NADPH-cytochrome c reductase were increased by PB treatment and cytochrome P-448 was induced by beta-NF treatment both in nuclei and in microsomes. The extents of inhibition of nuclear enzyme activities by the antibodies against corresponding microsomal enzymes were almost the same as those of the microsomal activities. It was concluded that a microsomal type electron transport system exists in rat liver nuclei, and that nuclear drug-oxidizing activities are inducible by PB or beta-NF as their microsomal counterparts are."}
{"id": "PMID:205536", "title": "Role of phospholipid in adrenaline-induced lipolysis and cyclic AMP production.", "content": "Lipid micelles consisting of a glyceride mixture (triolein, diolein, and monoolein) and lecithin bound adrenaline-14C more strongly than did micelles consisting of the glyceride mixture only. Lipid micelles consisting of the glyceride mixture and phosphatidic acid also bound adrenaline-14C effectivily, whereas lipid micelles consisting of the glyceride mixture and diglyceride, obtained from lecithin, did not bind the hormone strongly. Both phenoxybenzamine (an alpha- blocker) and propranolol (a beta-blocker) strongly inhibited the association between adrenaline-14C and lipid micelles consisting of the glyceride mixture and lecithin. Propranolol, inhibited adrenaline-induced lipolysis in both fat cells and fat globules, whereas, phenoxybenzamine, did not affect adrenaline-induced lipolysis. Both agents reduced adrenaline-induced adenyl-cyclase activation in fat cell ghosts. Phospholipid was also found to be related with adrenaline-mediated adenylcyclase activation.", "contents": "Role of phospholipid in adrenaline-induced lipolysis and cyclic AMP production. Lipid micelles consisting of a glyceride mixture (triolein, diolein, and monoolein) and lecithin bound adrenaline-14C more strongly than did micelles consisting of the glyceride mixture only. Lipid micelles consisting of the glyceride mixture and phosphatidic acid also bound adrenaline-14C effectivily, whereas lipid micelles consisting of the glyceride mixture and diglyceride, obtained from lecithin, did not bind the hormone strongly. Both phenoxybenzamine (an alpha- blocker) and propranolol (a beta-blocker) strongly inhibited the association between adrenaline-14C and lipid micelles consisting of the glyceride mixture and lecithin. Propranolol, inhibited adrenaline-induced lipolysis in both fat cells and fat globules, whereas, phenoxybenzamine, did not affect adrenaline-induced lipolysis. Both agents reduced adrenaline-induced adenyl-cyclase activation in fat cell ghosts. Phospholipid was also found to be related with adrenaline-mediated adenylcyclase activation."}
{"id": "PMID:205539", "title": "beta-adrenergic receptor and adenylate cyclase in transverse tubules of skeletal muscle.", "content": "Experiments were carried out to clarify the sites of action of beta-adrenergic agonists in skeletal muscle microsomes. Microsomes were fractionated into longitudinal reticulum, terminal cisternae, and isolated transverse tubules. Transverse tubules were selectively labeled and tracked with [3H]ouabain. beta-adrenergic receptor was identified by [3H]dihydroalprenolol binding. Assays of beta-adrenergic receptor, adenylate cyclase, and protein kinase-stimulated phosphorylation showed: 1) beta-adrenergic receptor was detected in transverse tubules with a receptor density of 0.61 pmol/mg of protein. No significant binding was detected in longitudinal reticulum or in terminal cisternae. 2) Isoproterenol-stimulated adenylate cyclase was present in microsomes but was similarly confined to the transverse tubular fraction. The activity of F- stimulated cyclase in transverse tubules was 2.3 nmol/mg of protein/min. 3) No phosphorylation of microsomes by cyclic AMP and protein kinase could be detected. We conclude that the action of epinephrine on skeletal muscle is mediated through receptors and adenylate cyclase in the external membrane.", "contents": "beta-adrenergic receptor and adenylate cyclase in transverse tubules of skeletal muscle. Experiments were carried out to clarify the sites of action of beta-adrenergic agonists in skeletal muscle microsomes. Microsomes were fractionated into longitudinal reticulum, terminal cisternae, and isolated transverse tubules. Transverse tubules were selectively labeled and tracked with [3H]ouabain. beta-adrenergic receptor was identified by [3H]dihydroalprenolol binding. Assays of beta-adrenergic receptor, adenylate cyclase, and protein kinase-stimulated phosphorylation showed: 1) beta-adrenergic receptor was detected in transverse tubules with a receptor density of 0.61 pmol/mg of protein. No significant binding was detected in longitudinal reticulum or in terminal cisternae. 2) Isoproterenol-stimulated adenylate cyclase was present in microsomes but was similarly confined to the transverse tubular fraction. The activity of F- stimulated cyclase in transverse tubules was 2.3 nmol/mg of protein/min. 3) No phosphorylation of microsomes by cyclic AMP and protein kinase could be detected. We conclude that the action of epinephrine on skeletal muscle is mediated through receptors and adenylate cyclase in the external membrane."}
{"id": "PMID:205549", "title": "The effect of tobacco smoke on the metabolism and function of rat alveolar macrophages.", "content": "Alveolar macrophages harvested by bronchopulmonary lavage from rats exposed to tobacco smoke for 30 days (\"smokers\") showed alterations in oxidative metabolism, lactate production and phagocytosis of inert starch particles when compared with control macrophages. Phagocytosis of viable Staphylococcus aureus was unaffected by tobacco smoke. Glucose oxidation measured by conversion of glucose-1-14C to 14CO2 moderately affected while oxidation of glucose-6-14C to 14CO2 was not. Smokers routinely yielded fewer cells than controls, though these cells contained approximately 17% more protein than did controls. Opsonization of particles was not necessary for macrophages from either smoker or control animals to manifest a respiratory burst and increased superoxide and hydrogen peroxide release during phagocytosis. The glycolytic inhibitors, sodium fluoride and iodoacetamide, while effectively blocking glycolysis, did not inhibit phagocytosis by macrophages from either group. The results reported clearly distinguish alveolar macrophages from other phagocytic cells (peritoneal macrophages and polymorphonuclear leukocytes) and suggest a state of non-specific activation caused by exposure to tobacco smoke.", "contents": "The effect of tobacco smoke on the metabolism and function of rat alveolar macrophages. Alveolar macrophages harvested by bronchopulmonary lavage from rats exposed to tobacco smoke for 30 days (\"smokers\") showed alterations in oxidative metabolism, lactate production and phagocytosis of inert starch particles when compared with control macrophages. Phagocytosis of viable Staphylococcus aureus was unaffected by tobacco smoke. Glucose oxidation measured by conversion of glucose-1-14C to 14CO2 moderately affected while oxidation of glucose-6-14C to 14CO2 was not. Smokers routinely yielded fewer cells than controls, though these cells contained approximately 17% more protein than did controls. Opsonization of particles was not necessary for macrophages from either smoker or control animals to manifest a respiratory burst and increased superoxide and hydrogen peroxide release during phagocytosis. The glycolytic inhibitors, sodium fluoride and iodoacetamide, while effectively blocking glycolysis, did not inhibit phagocytosis by macrophages from either group. The results reported clearly distinguish alveolar macrophages from other phagocytic cells (peritoneal macrophages and polymorphonuclear leukocytes) and suggest a state of non-specific activation caused by exposure to tobacco smoke."}
{"id": "PMID:205550", "title": "Serum-stimulated changes in calcium transport and distribution in mouse 3T3 cells and their modification by dibutyryl cyclic AMP.", "content": "Serum stimulation of quiescent 3T3 cells returns the cells to a proliferative state. Changes in Ca content, transport and distribution during the transition through G1 and S phase have been investigated following serum stimulation of these cells. 45 Ca exchange data indicate at least two kinetically defined cellular compartments for Ca; a rapidly exchanging component presumably representing surface Ca which is removable by EGTA and a slowly exchanging component presumably representing cytoplasmically located Ca. Previous studies (Tupper and Zorgniotti, '77) indicate that the approach to quiescence in the 3T3 cells is characterized by a large increase in the surface Ca component. The present data demonstrate that this component is rapidly lost following serum stimulation. Furthermore, the serum induces an 8-fold increase in Ca influx into the cytoplasmic compartment and a reduction in the unidirectional efflux rate coefficient for Ca. The increased Ca uptake peaks at approximately six hours (mid G1) and is accompanied by a parallel increase in cellular Ca. Prior to entrance of the cells into S phase (10-12 hours), Ca uptake declines. This is followed by a slower decline in cytoplasmic Ca levels. Simultaneous addition to fresh serum plus 0.5 mM dibutryl cAMP inhibits the entrance of the cells into S phase. Under these conditions the loss of surface Ca is not blocked. However, the presence of 0.5 mM dibutyryl cAMP inhibits the increase in Ca uptake and, in turn, diminishes the increase in cellular Ca following serum stimulation. In contrast, a low level of dibutyryl cAMP (0.1 mM) enhances progression through G1 phase but also reduces both Ca uptake and Ca content of the cells. The data suggest that the serum induced changes in Ca content and transport are linked to intracellular cyclic nucleotide levels and progression through G1 phase and that extracellular cAMP elevating agents may enhance of inhibit these interactions in a concentration dependent manner.", "contents": "Serum-stimulated changes in calcium transport and distribution in mouse 3T3 cells and their modification by dibutyryl cyclic AMP. Serum stimulation of quiescent 3T3 cells returns the cells to a proliferative state. Changes in Ca content, transport and distribution during the transition through G1 and S phase have been investigated following serum stimulation of these cells. 45 Ca exchange data indicate at least two kinetically defined cellular compartments for Ca; a rapidly exchanging component presumably representing surface Ca which is removable by EGTA and a slowly exchanging component presumably representing cytoplasmically located Ca. Previous studies (Tupper and Zorgniotti, '77) indicate that the approach to quiescence in the 3T3 cells is characterized by a large increase in the surface Ca component. The present data demonstrate that this component is rapidly lost following serum stimulation. Furthermore, the serum induces an 8-fold increase in Ca influx into the cytoplasmic compartment and a reduction in the unidirectional efflux rate coefficient for Ca. The increased Ca uptake peaks at approximately six hours (mid G1) and is accompanied by a parallel increase in cellular Ca. Prior to entrance of the cells into S phase (10-12 hours), Ca uptake declines. This is followed by a slower decline in cytoplasmic Ca levels. Simultaneous addition to fresh serum plus 0.5 mM dibutryl cAMP inhibits the entrance of the cells into S phase. Under these conditions the loss of surface Ca is not blocked. However, the presence of 0.5 mM dibutyryl cAMP inhibits the increase in Ca uptake and, in turn, diminishes the increase in cellular Ca following serum stimulation. In contrast, a low level of dibutyryl cAMP (0.1 mM) enhances progression through G1 phase but also reduces both Ca uptake and Ca content of the cells. The data suggest that the serum induced changes in Ca content and transport are linked to intracellular cyclic nucleotide levels and progression through G1 phase and that extracellular cAMP elevating agents may enhance of inhibit these interactions in a concentration dependent manner."}
{"id": "PMID:205552", "title": "Glucagon binding and adenylate cyclase activity in liver membranes from untreated and insulin-treated diabetic rats.", "content": "To investigate the role of hepatic glucagon receptors in the hypersensitivity to glucagon observed in insulin-deprived diabetics, liver plasma membranes were prepared from control rats and from streptozotocin-induced diabetic rats some of whom were treated with high-dose and low-dose insulin. The untreated diabetic animals exhibited hyperglycemia, weight loss, hypoinsulinemia, and hyperglucagonemia. High-dose insulin treatment (2 U Protamine-zinc-insulin/100 g per day) resulted in normoglycemia, normal weight gain, mild hyperinsulinemia, and return of glucagon levels toward base line. The low-dose (1 U protamine-zinc-insulin/100 g per day) insulin-treated diabetic group demonstrated chemical changes intermediate between the untreated and the high-dose insulin-treated animals. In liver plasma membranes from the untreated diabetic rats, specific binding of (125)I-glucagon was increased by 95%. Analysis of binding data suggested that the changes in glucagon binding were a consequence of alterations in binding capacity rather than changes in binding affinity. Furthermore, in the untreated diabetic rats, both basal and glucagon (2 muM)-stimulated adenylate cyclase activity were twofold higher than in controls. In the high-dose insulin-treated diabetic rats, glucagon binding and basal and glucagon-stimulated adenylate cyclase activity were normalized to control values, whereas low-dose insulin treatment resulted in changes intermediate between control and untreated diabetic rats. In contrast to glucagon-stimulated adenylate cyclase activity, fluoride-stimulated adenylate cyclase activity was similar in all groups of rats. Liver plasma membranes from untreated and insulin-treated diabetic animals degraded (125)I-glucagon to the same extent as control rats. The specific binding of (125)I-insulin in the untreated diabetic animals was 40% higher than in control rats. In low-dose insulin-treated diabetic rats, insulin binding was not significantly different from that of control rats, whereas in the high-dose insulin-treated group in whom plasma insulin was 70% above control levels, insulin binding was 30% lower than in control rats. These findings suggest that alterations in glucagon receptors may contribute to the augmented glycemic and ketonemic response to glucagon observed in insulin-deprived diabetics.", "contents": "Glucagon binding and adenylate cyclase activity in liver membranes from untreated and insulin-treated diabetic rats. To investigate the role of hepatic glucagon receptors in the hypersensitivity to glucagon observed in insulin-deprived diabetics, liver plasma membranes were prepared from control rats and from streptozotocin-induced diabetic rats some of whom were treated with high-dose and low-dose insulin. The untreated diabetic animals exhibited hyperglycemia, weight loss, hypoinsulinemia, and hyperglucagonemia. High-dose insulin treatment (2 U Protamine-zinc-insulin/100 g per day) resulted in normoglycemia, normal weight gain, mild hyperinsulinemia, and return of glucagon levels toward base line. The low-dose (1 U protamine-zinc-insulin/100 g per day) insulin-treated diabetic group demonstrated chemical changes intermediate between the untreated and the high-dose insulin-treated animals. In liver plasma membranes from the untreated diabetic rats, specific binding of (125)I-glucagon was increased by 95%. Analysis of binding data suggested that the changes in glucagon binding were a consequence of alterations in binding capacity rather than changes in binding affinity. Furthermore, in the untreated diabetic rats, both basal and glucagon (2 muM)-stimulated adenylate cyclase activity were twofold higher than in controls. In the high-dose insulin-treated diabetic rats, glucagon binding and basal and glucagon-stimulated adenylate cyclase activity were normalized to control values, whereas low-dose insulin treatment resulted in changes intermediate between control and untreated diabetic rats. In contrast to glucagon-stimulated adenylate cyclase activity, fluoride-stimulated adenylate cyclase activity was similar in all groups of rats. Liver plasma membranes from untreated and insulin-treated diabetic animals degraded (125)I-glucagon to the same extent as control rats. The specific binding of (125)I-insulin in the untreated diabetic animals was 40% higher than in control rats. In low-dose insulin-treated diabetic rats, insulin binding was not significantly different from that of control rats, whereas in the high-dose insulin-treated group in whom plasma insulin was 70% above control levels, insulin binding was 30% lower than in control rats. These findings suggest that alterations in glucagon receptors may contribute to the augmented glycemic and ketonemic response to glucagon observed in insulin-deprived diabetics."}
{"id": "PMID:205553", "title": "Genetics of the low density lipoprotein receptor. Diminished receptor activity in lymphocytes from heterozygotes with familial hypercholesterolemia.", "content": "Using circulating mononuclear cells as a readily available tissue and using the rate of high affinity degradation of 125-I-labeled low density lipoprotein (LDL) as an index of cell surface LDL receptor activity, we have measured receptor activity in cells from 53 individuals. This group includes 32 healthy subjects, 15 subjects with the heterozygous form of familial hypercholesterolemia, and 6 subjects with hyperlipidemic disorders other than familial hypercholesterolemia. 7 of the healthy subjects and 10 of the heterozygotes were members of a single large kindred with five-generation transmission of the mutant familial hypercholesterolemia gene. LDL receptor activity was assayed in blood mononuclear cells under two sets of conditions. First, 125I-LDL degradation was measured in purified lymphocytes that had been incubated for 3 days in the absence of lipoproteins so as to induce a high level of LDL receptor activity. Phase-contrast autoradiograms of cells incubated with 125I-LDL and electron micrographs of cells incubated with ferritin-labeled LDL confirmed the existence of LDL receptors on lymphocytes. Second, 125I-LDL degradation was measured in mixed mononuclear cells (85-90% lymphocytes and 5-15% monocytes) immediately after their isolation from the bloodstream. This assay represented an attempt to assess the number of receptors actually expressed on the cells when they were in the circulation. Under both sets of conditions, cells from the familial hypercholesterolemia heterozygotes expressed an average of about one-half the normal number of LDL receptors. The current findings are consistent with the conclusion that heterozygotes with familial hypercholesterolemia possess only one functional allele at the LDL receptor locus and that the consequent deficiency of LDL receptors produces the clinical syndrome of heterozygous familial hypercholesterolemia.", "contents": "Genetics of the low density lipoprotein receptor. Diminished receptor activity in lymphocytes from heterozygotes with familial hypercholesterolemia. Using circulating mononuclear cells as a readily available tissue and using the rate of high affinity degradation of 125-I-labeled low density lipoprotein (LDL) as an index of cell surface LDL receptor activity, we have measured receptor activity in cells from 53 individuals. This group includes 32 healthy subjects, 15 subjects with the heterozygous form of familial hypercholesterolemia, and 6 subjects with hyperlipidemic disorders other than familial hypercholesterolemia. 7 of the healthy subjects and 10 of the heterozygotes were members of a single large kindred with five-generation transmission of the mutant familial hypercholesterolemia gene. LDL receptor activity was assayed in blood mononuclear cells under two sets of conditions. First, 125I-LDL degradation was measured in purified lymphocytes that had been incubated for 3 days in the absence of lipoproteins so as to induce a high level of LDL receptor activity. Phase-contrast autoradiograms of cells incubated with 125I-LDL and electron micrographs of cells incubated with ferritin-labeled LDL confirmed the existence of LDL receptors on lymphocytes. Second, 125I-LDL degradation was measured in mixed mononuclear cells (85-90% lymphocytes and 5-15% monocytes) immediately after their isolation from the bloodstream. This assay represented an attempt to assess the number of receptors actually expressed on the cells when they were in the circulation. Under both sets of conditions, cells from the familial hypercholesterolemia heterozygotes expressed an average of about one-half the normal number of LDL receptors. The current findings are consistent with the conclusion that heterozygotes with familial hypercholesterolemia possess only one functional allele at the LDL receptor locus and that the consequent deficiency of LDL receptors produces the clinical syndrome of heterozygous familial hypercholesterolemia."}
{"id": "PMID:205554", "title": "Catabolism of very low density lipoprotein B apoprotein in man.", "content": "The turnover and the catabolic fate of the B apoprotein of very low density lipoprotein (VLDL-B) was studied in 15 normal and hyperlipidemic subjects using reinjected autologous VLDL labeled with radioiodine. The specific radioactivity-time curve of the B apoprotein in total VLDL (S(f)20-400) was multiexponential but conformed to a two-pool model during the first 48 h of catabolism. The flux was highest in several hypertriglyceridemic subjects. The mass of pool A exceeded the intravascular content of VLDL-B by 30% on average, indicating extravascular metabolism of VLDL. The two-pool model might reflect the input of several populations of particles or heterogeneity of catabolic processes or pools. The flux of B apoprotein was also measured in several subclasses of VLDL, in smaller intermediate density lipoproteins, and in low density lipoproteins (LDL). In three subjects the flux was similar in S(f) 60-400 and in S(f) 12-60 lipoproteins, suggesting that VLDL was catabolized at least to a particle in the density range S(f) 12-60. Subsequent catabolism appeared to proceed by two pathways: in normotriglyceridemic subjects, B apoprotein flux in the S(f) 20-400 and in S(f) 12-20 lipoproteins was similar, whereas in hypertriglyceridemic subjects flux through S(f) 12-20 accounted for only part of the VLDL-B flux. The flux of low density lipoprotein B apoprotein (LDL-B), which is believed to be derived from VLDL catabolism, was calculated from the area between the specific activity time curves of VLDL-B and LDL-B. In subjects with normal plasma triglyceride concentration, LDL-B flux was from 91% to 113% of that of VLDL-B; but in three hypertriglyceridemic subjects showing high rates of VLDL-B transport, LDL-B flux was only one-third that of VLDL-B. This suggests that when VLDL-B flux is high, VLDL is substantially catabolized by a route other than through LDL and possibly leaves the circulation as a particle in the S(f) 20-60 density range.", "contents": "Catabolism of very low density lipoprotein B apoprotein in man. The turnover and the catabolic fate of the B apoprotein of very low density lipoprotein (VLDL-B) was studied in 15 normal and hyperlipidemic subjects using reinjected autologous VLDL labeled with radioiodine. The specific radioactivity-time curve of the B apoprotein in total VLDL (S(f)20-400) was multiexponential but conformed to a two-pool model during the first 48 h of catabolism. The flux was highest in several hypertriglyceridemic subjects. The mass of pool A exceeded the intravascular content of VLDL-B by 30% on average, indicating extravascular metabolism of VLDL. The two-pool model might reflect the input of several populations of particles or heterogeneity of catabolic processes or pools. The flux of B apoprotein was also measured in several subclasses of VLDL, in smaller intermediate density lipoproteins, and in low density lipoproteins (LDL). In three subjects the flux was similar in S(f) 60-400 and in S(f) 12-60 lipoproteins, suggesting that VLDL was catabolized at least to a particle in the density range S(f) 12-60. Subsequent catabolism appeared to proceed by two pathways: in normotriglyceridemic subjects, B apoprotein flux in the S(f) 20-400 and in S(f) 12-20 lipoproteins was similar, whereas in hypertriglyceridemic subjects flux through S(f) 12-20 accounted for only part of the VLDL-B flux. The flux of low density lipoprotein B apoprotein (LDL-B), which is believed to be derived from VLDL catabolism, was calculated from the area between the specific activity time curves of VLDL-B and LDL-B. In subjects with normal plasma triglyceride concentration, LDL-B flux was from 91% to 113% of that of VLDL-B; but in three hypertriglyceridemic subjects showing high rates of VLDL-B transport, LDL-B flux was only one-third that of VLDL-B. This suggests that when VLDL-B flux is high, VLDL is substantially catabolized by a route other than through LDL and possibly leaves the circulation as a particle in the S(f) 20-60 density range."}
{"id": "PMID:205556", "title": "Free-sporing Cl. welchii in ordinary laboratory media and conditions.", "content": "A strain of Clostridium welchii produced spores in ordinary blood agar plates. Investigations confirmed that it was the character of this particular strain and that the laboratory media were not inducing sporulation. During a period of 12 months a total of 100 strains of Cl. welchii were studied. None of them produced spores in ordinary laboratory media and conditions when examined microscopically.", "contents": "Free-sporing Cl. welchii in ordinary laboratory media and conditions. A strain of Clostridium welchii produced spores in ordinary blood agar plates. Investigations confirmed that it was the character of this particular strain and that the laboratory media were not inducing sporulation. During a period of 12 months a total of 100 strains of Cl. welchii were studied. None of them produced spores in ordinary laboratory media and conditions when examined microscopically."}
{"id": "PMID:205555", "title": "Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients.", "content": "Human polyomavirus (BK) was detected in two renal allograft recipients as a result of routine examination of Papanicolaou-stained smears of urinary sediment in the light microscope. Infection with this recently identified virus was confirmed by virus isolation and electron microscopy. The cytological, histological, and ultrastructural changes due to the virus are described, and virus excretion is correlated with the clinical progress of the patients and the pathological findings. The transplant ureters in both patients were found to be ulcerated and stenosed, and virus-infected cells were observed in the ureteric epithelium. We suggest that the administration of high-dose steroids in transplantation may permit active infection with human polyomavirus to occur in ureteric epithelium which has been damaged by ischaemia or inflammation.", "contents": "Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients. Human polyomavirus (BK) was detected in two renal allograft recipients as a result of routine examination of Papanicolaou-stained smears of urinary sediment in the light microscope. Infection with this recently identified virus was confirmed by virus isolation and electron microscopy. The cytological, histological, and ultrastructural changes due to the virus are described, and virus excretion is correlated with the clinical progress of the patients and the pathological findings. The transplant ureters in both patients were found to be ulcerated and stenosed, and virus-infected cells were observed in the ureteric epithelium. We suggest that the administration of high-dose steroids in transplantation may permit active infection with human polyomavirus to occur in ureteric epithelium which has been damaged by ischaemia or inflammation."}
{"id": "PMID:205557", "title": "Chemical and kinetic study of the lipoproteins in abetalipoproteinaemic plasma.", "content": "Abetalipoproteinaemic plasma lipoproteins were fractionated by molecular sieve chromatography into two classes on the basis of size. Each class had the same chemical and immunochemical composition and seemed to be interconvertible in vitro, presumably as a result of aggregation/disaggregation. The low levels of circulating apolipoprotein A-I found in abetalipoproteinaemic subjects have been shown by kinetic analysis to result from reduced synthesis of the apoprotein and not from increased catabolism or redistribution between vascular and extravascular compartments.", "contents": "Chemical and kinetic study of the lipoproteins in abetalipoproteinaemic plasma. Abetalipoproteinaemic plasma lipoproteins were fractionated by molecular sieve chromatography into two classes on the basis of size. Each class had the same chemical and immunochemical composition and seemed to be interconvertible in vitro, presumably as a result of aggregation/disaggregation. The low levels of circulating apolipoprotein A-I found in abetalipoproteinaemic subjects have been shown by kinetic analysis to result from reduced synthesis of the apoprotein and not from increased catabolism or redistribution between vascular and extravascular compartments."}
{"id": "PMID:205559", "title": "Multiple effects of N, N' dicyclohexyl carbodiimide on the beta-adrenergic receptor--adenylate cyclase system in frog erythrocytes.", "content": "Treatment of frog erythrocytes with N,N' dicyclohexylcarbodiimide (DCCD) leads to a loss of catecholamine stimulated adenylate cyclase activity without any decrease in fluoride or PGE1 stimulated cyclase. However, the concentrations of the reagent which inhibit catecholamine sensitive adenylate cyclase activity are 10 fold lower than those which inhibit specific [3H]dihydroalprenolol ([3H]DHA) beta-adrenergic receptor binding. By contrast binding of the readiolabeled beta-adrenergic agonist [3H]hydroxybenzylisoproterenol ([3H]HBI) is considerably more sensitive than antagonist binding to the effects of DCCD. The data suggest that low concentrations of the reagent may modify the effector portion of the beta-adrenergic receptor leading to functional uncoupling of the beta-receptor adenylate cyclase system. At higher concentrations of the reagent the  ligand bidning site of the beta-receptor appears also to be altered.", "contents": "Multiple effects of N, N' dicyclohexyl carbodiimide on the beta-adrenergic receptor--adenylate cyclase system in frog erythrocytes. Treatment of frog erythrocytes with N,N' dicyclohexylcarbodiimide (DCCD) leads to a loss of catecholamine stimulated adenylate cyclase activity without any decrease in fluoride or PGE1 stimulated cyclase. However, the concentrations of the reagent which inhibit catecholamine sensitive adenylate cyclase activity are 10 fold lower than those which inhibit specific [3H]dihydroalprenolol ([3H]DHA) beta-adrenergic receptor binding. By contrast binding of the readiolabeled beta-adrenergic agonist [3H]hydroxybenzylisoproterenol ([3H]HBI) is considerably more sensitive than antagonist binding to the effects of DCCD. The data suggest that low concentrations of the reagent may modify the effector portion of the beta-adrenergic receptor leading to functional uncoupling of the beta-receptor adenylate cyclase system. At higher concentrations of the reagent the  ligand bidning site of the beta-receptor appears also to be altered."}
{"id": "PMID:205560", "title": "On the role of the cAMP and cGMP-dependent protein kinases in cell function.", "content": "Cyclic AMP and cGMP-dependent protein kinases have many similarities in physical and kinetic properties. Thus, the two enzymes appear to be homologous proteins, even though the subunit compositions of the two enzymes differ. Of several possible evolutionary schemes, two likely ones are proposed: (i) the ancestral protein kinase was composed of a single type of subunit which evolved into separate regulatory and catalytic subunits by gene splitting; or (ii) the ancestral protein kinase was composed of separate regulatory and catalytic subunits which evolved into a single type of subunit by gene fusion. The evolutionary parallelism poses interesting questions on the functional relatwonships between the two enzymes. Although, there is overlapping substrate specificity between the two kinases, the cAMP kinase is generally a more efficient and versatile catalyst than the cGMP kinase. This difference in catalytic versatility could have offered an evolutionary advantage to the cAMP kinase, and could explain the more widespread distribution of this enzyme in mammalian tissues. The cGMP kinase is proposed to be a more specific enzyme than the cAMP kinase. This implies a less diverse role for cGMP in the regulation of cell function.", "contents": "On the role of the cAMP and cGMP-dependent protein kinases in cell function. Cyclic AMP and cGMP-dependent protein kinases have many similarities in physical and kinetic properties. Thus, the two enzymes appear to be homologous proteins, even though the subunit compositions of the two enzymes differ. Of several possible evolutionary schemes, two likely ones are proposed: (i) the ancestral protein kinase was composed of a single type of subunit which evolved into separate regulatory and catalytic subunits by gene splitting; or (ii) the ancestral protein kinase was composed of separate regulatory and catalytic subunits which evolved into a single type of subunit by gene fusion. The evolutionary parallelism poses interesting questions on the functional relatwonships between the two enzymes. Although, there is overlapping substrate specificity between the two kinases, the cAMP kinase is generally a more efficient and versatile catalyst than the cGMP kinase. This difference in catalytic versatility could have offered an evolutionary advantage to the cAMP kinase, and could explain the more widespread distribution of this enzyme in mammalian tissues. The cGMP kinase is proposed to be a more specific enzyme than the cAMP kinase. This implies a less diverse role for cGMP in the regulation of cell function."}
{"id": "PMID:205561", "title": "8-P-Chlorophenylthio-cyclic AMP: a potent partial simulator of antidiuretic hormone action.", "content": "In the toad urinary bladder 8-p-chlorophenylthio-cyclic AMP mimics the stimulatory effects of antidiuretic hormone on osmotic water permeability, 3H2O diffusion, and transepithelial sodium transport; but unlike the hormone does not cause an increase in urea permeability. Trheshold activation for the hydroosmotic response is observed at 1 micrometer and full activation at 100 micrometer. These results suggest that cyclic AMP may not mediate all the physiological effects of antidiuretic hormone and that this highly potent cyclic AMP analog may be useful in elucidating the precise role of cyclic AMP in other biomediate hormone action.", "contents": "8-P-Chlorophenylthio-cyclic AMP: a potent partial simulator of antidiuretic hormone action. In the toad urinary bladder 8-p-chlorophenylthio-cyclic AMP mimics the stimulatory effects of antidiuretic hormone on osmotic water permeability, 3H2O diffusion, and transepithelial sodium transport; but unlike the hormone does not cause an increase in urea permeability. Trheshold activation for the hydroosmotic response is observed at 1 micrometer and full activation at 100 micrometer. These results suggest that cyclic AMP may not mediate all the physiological effects of antidiuretic hormone and that this highly potent cyclic AMP analog may be useful in elucidating the precise role of cyclic AMP in other biomediate hormone action."}
{"id": "PMID:205562", "title": "Activation of cyclic AMP-dependent protein kinase(s) by growth hormone in the liver and adrenal gland of the rat.", "content": "A single dose of growth hormone (10 mg/kg, i.p.) was injected into male weanling rats (50--60 g), and the temporal changes in cyclic AMP concentration, protein kinase activation, and ornithine decarboxylase activation were measured in the liver and adrenal gland. The level of cyclic AMP did not change significantly from control values in either liver or adrenal following growth hormone administration. Cyclic AMP-dependent protein kinase(s); however, was markedly activated in liver and adrenal within 30 min. Protein kinase remained activated for more than 4 hr in the liver, while activation of protein kinase in the adrenal returned to control value within 2 hr. Ornithine decarboxylase activity was elevated 20-fold in liver within 4 hr of injection and was increased 7- to 8-fold in be adrenal within l hr. These observations are discussed with regard to the generality of the role of cyclic AMP as the second messenger for target-specifici trophic hormone action and the significance of protein kinase activiation as an index of the cyclic nucleotide involvement in the growth response.", "contents": "Activation of cyclic AMP-dependent protein kinase(s) by growth hormone in the liver and adrenal gland of the rat. A single dose of growth hormone (10 mg/kg, i.p.) was injected into male weanling rats (50--60 g), and the temporal changes in cyclic AMP concentration, protein kinase activation, and ornithine decarboxylase activation were measured in the liver and adrenal gland. The level of cyclic AMP did not change significantly from control values in either liver or adrenal following growth hormone administration. Cyclic AMP-dependent protein kinase(s); however, was markedly activated in liver and adrenal within 30 min. Protein kinase remained activated for more than 4 hr in the liver, while activation of protein kinase in the adrenal returned to control value within 2 hr. Ornithine decarboxylase activity was elevated 20-fold in liver within 4 hr of injection and was increased 7- to 8-fold in be adrenal within l hr. These observations are discussed with regard to the generality of the role of cyclic AMP as the second messenger for target-specifici trophic hormone action and the significance of protein kinase activiation as an index of the cyclic nucleotide involvement in the growth response."}
{"id": "PMID:205563", "title": "Beta-adrenergic receptors and myogenesis.", "content": "The rat myogenic cell line, L8, contains a beta-adrenergic catecholamine-sensitive adenylate cyclase. Prior to cell fusion, and continuing thereafter, beta-adrenergic sites, as determined by the stereospecific binding of (125I)-hydroxybenqylpindolol, I1(125I)IHYP] increases from 470 to 2000 sites/cell. There is also an increase in adenylate cyclase (2-5 fold) and endogenous cAMP (5-30 fold) following stimulation by catecholamine. The dissociation constant (KD) of (125I)IHYP for unfused and fused cell-homogenates, as determined by estimation with Scatchard analysis, by direct determination at receptor concentrations well below the KD, or by association (4.6 X 10(8) M-1 min-1); and dissociation (0.028 min-1) kinetics; ranged from about 40 to 70 pM. The acquisition of beta-receptors prior to fusion in L8 cells may implicate this system in the regulation of myogenesis.", "contents": "Beta-adrenergic receptors and myogenesis. The rat myogenic cell line, L8, contains a beta-adrenergic catecholamine-sensitive adenylate cyclase. Prior to cell fusion, and continuing thereafter, beta-adrenergic sites, as determined by the stereospecific binding of (125I)-hydroxybenqylpindolol, I1(125I)IHYP] increases from 470 to 2000 sites/cell. There is also an increase in adenylate cyclase (2-5 fold) and endogenous cAMP (5-30 fold) following stimulation by catecholamine. The dissociation constant (KD) of (125I)IHYP for unfused and fused cell-homogenates, as determined by estimation with Scatchard analysis, by direct determination at receptor concentrations well below the KD, or by association (4.6 X 10(8) M-1 min-1); and dissociation (0.028 min-1) kinetics; ranged from about 40 to 70 pM. The acquisition of beta-receptors prior to fusion in L8 cells may implicate this system in the regulation of myogenesis."}
{"id": "PMID:205564", "title": "Effect of adrenocorticotropic hormone on plasma glucocorticoids and antidiuretic hormone of cattle exposed to 20 and 33 C.", "content": "Four open, dry Holstein cows in the University of Missouri Climatic Laboratory were used to study the effect of adrenocorticotropic hormone administration on glucocorticoids and antidiuretic hormone of plasma in two reversal trials at thermoneutral (20 C, 50% relative humidity) and heat (33 C, 50% relative humidity) conditions. Average glucocorticoids (saline versus adrenocorticotropic hormone) at thermoneutral were 8.3 and 41.2 ng/ml while values for heat were 6.2 and 40.4 ng/ml. The effect of heat on glucocorticoids of plasma was not significant. Injection of adrenocorticotropic hormone under thermoneutrality and heat caused a marked increase in antidiuretic hormone within 5 min which lasted to 120 min. At thermoneutral average antidiuretic hormone levels (saline versus adrenocorticotropic hormone) were .5 and 1.9 pg/ml while values for heat were 1.8 and 3.6 pg/ml. Antidiuretic hormone concentrations under heat were higher than thermoneutral in cows injected with saline and andrenocorticotropic hormone. The fast response of antidiuretic hormone of plasma to exogenous adrenocorticotropic hormone suggests that adrenocorticotropic hormone might act directly at higher levels of the central nervous system causing release of antidiuretic hormone.", "contents": "Effect of adrenocorticotropic hormone on plasma glucocorticoids and antidiuretic hormone of cattle exposed to 20 and 33 C. Four open, dry Holstein cows in the University of Missouri Climatic Laboratory were used to study the effect of adrenocorticotropic hormone administration on glucocorticoids and antidiuretic hormone of plasma in two reversal trials at thermoneutral (20 C, 50% relative humidity) and heat (33 C, 50% relative humidity) conditions. Average glucocorticoids (saline versus adrenocorticotropic hormone) at thermoneutral were 8.3 and 41.2 ng/ml while values for heat were 6.2 and 40.4 ng/ml. The effect of heat on glucocorticoids of plasma was not significant. Injection of adrenocorticotropic hormone under thermoneutrality and heat caused a marked increase in antidiuretic hormone within 5 min which lasted to 120 min. At thermoneutral average antidiuretic hormone levels (saline versus adrenocorticotropic hormone) were .5 and 1.9 pg/ml while values for heat were 1.8 and 3.6 pg/ml. Antidiuretic hormone concentrations under heat were higher than thermoneutral in cows injected with saline and andrenocorticotropic hormone. The fast response of antidiuretic hormone of plasma to exogenous adrenocorticotropic hormone suggests that adrenocorticotropic hormone might act directly at higher levels of the central nervous system causing release of antidiuretic hormone."}
{"id": "PMID:205565", "title": "Changes in blood and urine composition from feeding polybrominated biphenyls to pregnant Holstein heifers.", "content": "The toxicity of a commercial preparation of polybrominated biphenyl was determined in 24 pregnant Holstein heifers that were alloted randomly to one of four experimental groups given 0 (I), .25 (II), 250 (III), and 25,000 (IV) mg per day of fireMaster BP-6 for 60 days or until the animals became moribund. Clinicopathologic determinations were on day -1 prior to dosing, days 15, 30 and 60 during dosing, and following dosing on days 80, 110, 150, and 190 from start of dosing. In addition, samples were collected from moribund heifers of Group IV immediately prior to necropsy. Toxicity was not evident in heifers in Groups I, II, or III. Toxicity was induced in heifers in Group IV. Glutamic-oxaloacetic transaminase of serum was increased and calcium decreased as early as day 15 whereas significant increases in lactate dehydrogenase, urea nitrogen, and bilirubin, and decreases in albumin were not observed until day 30 in heifers of Group IV. Analysis of urine from moribund heifers of Group IV revealed moderate proteinuria and decreased specific gravity. Evaluation of clinicopathologic data has suggested that the polybrominated biphenyls fed were renal toxins with no clear evidence of hepatotoxicity.", "contents": "Changes in blood and urine composition from feeding polybrominated biphenyls to pregnant Holstein heifers. The toxicity of a commercial preparation of polybrominated biphenyl was determined in 24 pregnant Holstein heifers that were alloted randomly to one of four experimental groups given 0 (I), .25 (II), 250 (III), and 25,000 (IV) mg per day of fireMaster BP-6 for 60 days or until the animals became moribund. Clinicopathologic determinations were on day -1 prior to dosing, days 15, 30 and 60 during dosing, and following dosing on days 80, 110, 150, and 190 from start of dosing. In addition, samples were collected from moribund heifers of Group IV immediately prior to necropsy. Toxicity was not evident in heifers in Groups I, II, or III. Toxicity was induced in heifers in Group IV. Glutamic-oxaloacetic transaminase of serum was increased and calcium decreased as early as day 15 whereas significant increases in lactate dehydrogenase, urea nitrogen, and bilirubin, and decreases in albumin were not observed until day 30 in heifers of Group IV. Analysis of urine from moribund heifers of Group IV revealed moderate proteinuria and decreased specific gravity. Evaluation of clinicopathologic data has suggested that the polybrominated biphenyls fed were renal toxins with no clear evidence of hepatotoxicity."}
{"id": "PMID:205567", "title": "Activation of human B lymphocytes VII. the regulatory effect of cyclic adenosine monophosphate on human B cell activation.", "content": "Cyclic adenosine monophosphate (cAMP) has been demonstrated to play an integral role in the regulation of B cell activation. By employing a plaque-forming cell (PFC) assay for polyclonal activation of human B lymphocytes, it was demonstrated that dibutyryl cyclic adenosine monophosphate (DB-cAMP) markedly increased the PFC response of pokeweed mitogen (PWM)--stimulated lymphocytes. Inducers of intracellular cAMP effected a comparable enhancement. Co-cultures of fresh lymphocytes with autologous T cells which had been pre-incubated with DB-cAMP produced an enhancement of B cell activation by a selective effect on the T cells. The mechanism of action of this enhancement of the B cell response is most likely a relative increase in helper T cell function resulting from a selective inhibition of suppressor T cells.", "contents": "Activation of human B lymphocytes VII. the regulatory effect of cyclic adenosine monophosphate on human B cell activation. Cyclic adenosine monophosphate (cAMP) has been demonstrated to play an integral role in the regulation of B cell activation. By employing a plaque-forming cell (PFC) assay for polyclonal activation of human B lymphocytes, it was demonstrated that dibutyryl cyclic adenosine monophosphate (DB-cAMP) markedly increased the PFC response of pokeweed mitogen (PWM)--stimulated lymphocytes. Inducers of intracellular cAMP effected a comparable enhancement. Co-cultures of fresh lymphocytes with autologous T cells which had been pre-incubated with DB-cAMP produced an enhancement of B cell activation by a selective effect on the T cells. The mechanism of action of this enhancement of the B cell response is most likely a relative increase in helper T cell function resulting from a selective inhibition of suppressor T cells."}
{"id": "PMID:205608", "title": "LPS-or 8Br-cyclic AMP-induced production of T cell-activating factor(s) in macrophage tumor cell line J774.1.", "content": "The macrophage tumor cell line J774.1 replaced the function of normal macrophages in the induction of polyclonal killer T cells with 2-mercaptoethanol. J774.1 does not normally release soluble factor(s) which we have shown to be responsible for the differentiation of T cells to killer T cells. However, stimulation of J774.1 with LPS induced soluble factor(s) for T cell activation. An optimum concentration of LPS for the production of soluble factor(s) was 1 to 10 microgram/ml, which completely inhibited growth of the tumor cells. The production of soluble factor(s) was observed within 6 hr after LPS stimulation and reached its maximum level at 24 hr. Incubation of the cell line with 8Br-cyclic AMP and theophylline induced soluble factor(s), suggesting that LPS stimulation induced an increase in intracellular cyclic AMP which leads to the synthesis of soluble factor(s).", "contents": "LPS-or 8Br-cyclic AMP-induced production of T cell-activating factor(s) in macrophage tumor cell line J774.1. The macrophage tumor cell line J774.1 replaced the function of normal macrophages in the induction of polyclonal killer T cells with 2-mercaptoethanol. J774.1 does not normally release soluble factor(s) which we have shown to be responsible for the differentiation of T cells to killer T cells. However, stimulation of J774.1 with LPS induced soluble factor(s) for T cell activation. An optimum concentration of LPS for the production of soluble factor(s) was 1 to 10 microgram/ml, which completely inhibited growth of the tumor cells. The production of soluble factor(s) was observed within 6 hr after LPS stimulation and reached its maximum level at 24 hr. Incubation of the cell line with 8Br-cyclic AMP and theophylline induced soluble factor(s), suggesting that LPS stimulation induced an increase in intracellular cyclic AMP which leads to the synthesis of soluble factor(s)."}
{"id": "PMID:205610", "title": "The central nervous system-associated immune response to parainfluenza type I virus in mice.", "content": "The immune response in the cerebrospinal fluid (CSF) and serum of BALB/c mice was compared after intracerebral (i.c.) inoculation with inactivated parainfluenza type 1 virus. The antiviral antibody response in CSF peaked approximately 11 days after primary i.c. inoculation coinciding with or even slightly preceding the response in the serum. Prior extracerebral priming of the mice by the intranasal or i.v. route did not alter the kinetics of the response in CSF. However, the antibody response in CSF after i.c. inoculation was accelerated if the mice were primed previously by the i.c. route. In all instances, CSF and serum differed markedly with regard to the isotype composition, which was characterized by a 20- to 80-fold increase in IgA over IgG1 and IgG2 in CSF. Taken together, the results prove that part of the antiviral antibodies in CSF are locally produced. In addition, the results indicate that after primary i.c. inoculation with virus, the CNS acquired immunocompetence with regard to the secondary anti-parainfluenza response.", "contents": "The central nervous system-associated immune response to parainfluenza type I virus in mice. The immune response in the cerebrospinal fluid (CSF) and serum of BALB/c mice was compared after intracerebral (i.c.) inoculation with inactivated parainfluenza type 1 virus. The antiviral antibody response in CSF peaked approximately 11 days after primary i.c. inoculation coinciding with or even slightly preceding the response in the serum. Prior extracerebral priming of the mice by the intranasal or i.v. route did not alter the kinetics of the response in CSF. However, the antibody response in CSF after i.c. inoculation was accelerated if the mice were primed previously by the i.c. route. In all instances, CSF and serum differed markedly with regard to the isotype composition, which was characterized by a 20- to 80-fold increase in IgA over IgG1 and IgG2 in CSF. Taken together, the results prove that part of the antiviral antibodies in CSF are locally produced. In addition, the results indicate that after primary i.c. inoculation with virus, the CNS acquired immunocompetence with regard to the secondary anti-parainfluenza response."}
{"id": "PMID:205613", "title": "The distribution of the inherited Hl 1 and R 67 antigens on rabbit serum high density lipoprotein (HDL) particles.", "content": "Qualitative and quantitative analysis of the distribution of Hl 1 antigen and R 67 antigen on high density lipoprotein (HDL) particles were conducted on six rabbit sera. The Hl 1 antigen showed non-identity with A-I-containing HDL particles, and antiserum to Hl 1 did not remove A-I-containing HDL particles. The R 67 antigen showed partial identity with A-I-containing HDL particles. Antiserum to R 67 antigen removed 30--40% of A-I-containing HDL particles from the sera of animals which were heterozygous for R 67, and 65% of the A-I-containing HDL particles from the serum of one R67 homozygous animal.", "contents": "The distribution of the inherited Hl 1 and R 67 antigens on rabbit serum high density lipoprotein (HDL) particles. Qualitative and quantitative analysis of the distribution of Hl 1 antigen and R 67 antigen on high density lipoprotein (HDL) particles were conducted on six rabbit sera. The Hl 1 antigen showed non-identity with A-I-containing HDL particles, and antiserum to Hl 1 did not remove A-I-containing HDL particles. The R 67 antigen showed partial identity with A-I-containing HDL particles. Antiserum to R 67 antigen removed 30--40% of A-I-containing HDL particles from the sera of animals which were heterozygous for R 67, and 65% of the A-I-containing HDL particles from the serum of one R67 homozygous animal."}
{"id": "PMID:205614", "title": "Purification and partial characterization of the apoA-I of rabbit high density lipoprotein.", "content": "Purification of apoA-I from rabbit high density lipoproteins (HDL) gave one single band in sodium dodecylsulphate-polyacrylamide disc electrophoresis and reacted only with antiserum to apoA-I. The molecular weight was about 25000. The amino acid composition of rabbit ,poA-I gave a difference index of 7.4 compared to human apoA-I and of 6.5 compared to dog apoA-I. Of the three carboxy terminal amino acid residues the rabbit protein has one in common with the dog. The amino acid sequence of twenty-nine amino terminal residues showed 62% homology with the human protein; a minimum of thirteen base changes were required in the DNA sequences that encoded these two proteins. When the same sequence was compared with dog apoA-I, it was found that ten base changes would be sufficient to account for the differences between the proteins.", "contents": "Purification and partial characterization of the apoA-I of rabbit high density lipoprotein. Purification of apoA-I from rabbit high density lipoproteins (HDL) gave one single band in sodium dodecylsulphate-polyacrylamide disc electrophoresis and reacted only with antiserum to apoA-I. The molecular weight was about 25000. The amino acid composition of rabbit ,poA-I gave a difference index of 7.4 compared to human apoA-I and of 6.5 compared to dog apoA-I. Of the three carboxy terminal amino acid residues the rabbit protein has one in common with the dog. The amino acid sequence of twenty-nine amino terminal residues showed 62% homology with the human protein; a minimum of thirteen base changes were required in the DNA sequences that encoded these two proteins. When the same sequence was compared with dog apoA-I, it was found that ten base changes would be sufficient to account for the differences between the proteins."}
{"id": "PMID:205615", "title": "Cyclic nucleotide-phosphodiesterase in the uninvolved and involved skin of psoriasis.", "content": "In the present study we have compared cyclic nucleotide-phosphodiesterase activities and affinity of phosphodiesterase for substrates (Km) in enzyme preparations obtained from the involved and uninvolved skin of psoriatic patients. With crude skin homogenates we consistently obtained two Km values (high and low) for both the involved and uninvolved, and both Km values were nearly identical between the involved and uninvolved. The same conclusion is also drawn from the Km determinations with partially purified preparations. Cyclic AMP-phosphodiesterase activities with crude homogenates showed no statistically significant differences between the involved and the uninvolved skin. However, when cyclic AMP- and cyclic GMP-phosphodiesterase activities were compared with a highly sensitive assay method in \"pure\" epidermal samples, which were microdissected free from stratum corneum, dermis and skin appendages, the involved skin contained 40% more activity of the low Km enzyme and 100% more of the high Km enzyme of both cyclic AMP- and cyclic GMP-phosphodiesterase. It is suggested that this may be due to a higher proportion of germinative cells in the lesional epidermis.", "contents": "Cyclic nucleotide-phosphodiesterase in the uninvolved and involved skin of psoriasis. In the present study we have compared cyclic nucleotide-phosphodiesterase activities and affinity of phosphodiesterase for substrates (Km) in enzyme preparations obtained from the involved and uninvolved skin of psoriatic patients. With crude skin homogenates we consistently obtained two Km values (high and low) for both the involved and uninvolved, and both Km values were nearly identical between the involved and uninvolved. The same conclusion is also drawn from the Km determinations with partially purified preparations. Cyclic AMP-phosphodiesterase activities with crude homogenates showed no statistically significant differences between the involved and the uninvolved skin. However, when cyclic AMP- and cyclic GMP-phosphodiesterase activities were compared with a highly sensitive assay method in \"pure\" epidermal samples, which were microdissected free from stratum corneum, dermis and skin appendages, the involved skin contained 40% more activity of the low Km enzyme and 100% more of the high Km enzyme of both cyclic AMP- and cyclic GMP-phosphodiesterase. It is suggested that this may be due to a higher proportion of germinative cells in the lesional epidermis."}
{"id": "PMID:205616", "title": "Cyclic AMP accumulation in psoriatic skin: differential responses to histamine, AMP, and einephrine by the uninvolved and involved epidermis.", "content": "Using the uninvolved and involved skin from psoriatic patients, we investigated the effects of histamine and AMP (or adenosine) in vitro on the intracellular cyclic AMP levels. Both agents activated adenylate cyclase of the uninvolved and involved resulting in the accumulation of cyclic AMP. Without a cyclic nucleotide phosphodiesterase (PDE) inhibitor, these responses were biphasic and the maximal accumulation was observed in 5 min. With the PDE inhibitor both responses were markedly potentiated and high levels of cyclic AMP were observed for more than 20 min. The response to histamine by the involved skin was much greater than that by the uninvolved. The degree of the response to adenosine was approximately equal. In accordance with our previous work, the response to epinephrine by the involved skin was much less than that by the uninvolved. Thus adenylate cyclases of involved skin from psoriatic patients exhibit a markedly diminished response to epinephrine while at the same time exhibiting a markedly enhanced response to histamine. This precludes the possibility that the unresponsiveness to epinephrine can be due to a generalized inability of the epidermal psoriatic plaque cell to make a functioning cell membrane.", "contents": "Cyclic AMP accumulation in psoriatic skin: differential responses to histamine, AMP, and einephrine by the uninvolved and involved epidermis. Using the uninvolved and involved skin from psoriatic patients, we investigated the effects of histamine and AMP (or adenosine) in vitro on the intracellular cyclic AMP levels. Both agents activated adenylate cyclase of the uninvolved and involved resulting in the accumulation of cyclic AMP. Without a cyclic nucleotide phosphodiesterase (PDE) inhibitor, these responses were biphasic and the maximal accumulation was observed in 5 min. With the PDE inhibitor both responses were markedly potentiated and high levels of cyclic AMP were observed for more than 20 min. The response to histamine by the involved skin was much greater than that by the uninvolved. The degree of the response to adenosine was approximately equal. In accordance with our previous work, the response to epinephrine by the involved skin was much less than that by the uninvolved. Thus adenylate cyclases of involved skin from psoriatic patients exhibit a markedly diminished response to epinephrine while at the same time exhibiting a markedly enhanced response to histamine. This precludes the possibility that the unresponsiveness to epinephrine can be due to a generalized inability of the epidermal psoriatic plaque cell to make a functioning cell membrane."}
{"id": "PMID:205617", "title": "An immunoelectron microscopic localization of wart associated antigens present in human papilloma virus (HPV) infected cells.", "content": "Wart associated antigens were observed by the indirect immunoperoxidase technique in light and electron microscopy. Positive reaction products could be found in the nuclei of wart cells, in which virus particles were labeled with a specific immune rabbit serum and with human sera from patients with warts. Tissue antigens, differing from the viral labeled inclusions, were detected within the cytoplasm of some infected cells, by means of IgM and IgG antibodies from patients with warts. In these particular cells the positive reaction occurred in irregular patterns giving microgranular precipitates, which suggests that the antigen was not uniform. No staining was observed on the cell surface. This study has shown direct immunomorphological evidence in vivo of a specific immune reaction in man directed against whole virus and wart specific cellular antigens.", "contents": "An immunoelectron microscopic localization of wart associated antigens present in human papilloma virus (HPV) infected cells. Wart associated antigens were observed by the indirect immunoperoxidase technique in light and electron microscopy. Positive reaction products could be found in the nuclei of wart cells, in which virus particles were labeled with a specific immune rabbit serum and with human sera from patients with warts. Tissue antigens, differing from the viral labeled inclusions, were detected within the cytoplasm of some infected cells, by means of IgM and IgG antibodies from patients with warts. In these particular cells the positive reaction occurred in irregular patterns giving microgranular precipitates, which suggests that the antigen was not uniform. No staining was observed on the cell surface. This study has shown direct immunomorphological evidence in vivo of a specific immune reaction in man directed against whole virus and wart specific cellular antigens."}
{"id": "PMID:205621", "title": "Biochemical characterization of pituitary-dependent hyperadrenocorticism in the dog.", "content": "The biochemical characterization of 22 cases of pituitary-dependent hyperadrenocorticism in the dog, is reported. The principal characteristics of the disease include excessive and non-rhythmic production of cortisol, decreased sensitivity of the hypothalamic-pituitary system to the suppressive effects of dexamethasone, decreased responsiveness of the pituitary-adrenocortical system to the stimulus of insulin-induced hypoglycaemia and increased responsiveness of the system to stimulation with lysine-vasopressin. From these observations it is concluded that pituitary-dependent hyperadrenocorticism in the dog is a valid model for study of the pathogenesis of the disease in man. For the diagnosis of hyperadrenocorticism itself, the measurement of the concentration of corticosteroids in a single sample of plasma obtained 8 h after intravenous injection of 0.01 mg dexamethasone/kg was sufficient. The level of 11-hydroxycorticosteroids was less than 140 nmol/1 plasma in normal dogs, whereas higher values were found in dogs with hyperadrenocorticism. For purposes of differential diagnosis, measurement of the level of corticosteroids in the plasma both before and 4 h after intravenous injection of 0.05 mg dexamethasone/kg is adequage: suppression is obtained only in cases of pituitary-dependent hyperadrenocorticism.", "contents": "Biochemical characterization of pituitary-dependent hyperadrenocorticism in the dog. The biochemical characterization of 22 cases of pituitary-dependent hyperadrenocorticism in the dog, is reported. The principal characteristics of the disease include excessive and non-rhythmic production of cortisol, decreased sensitivity of the hypothalamic-pituitary system to the suppressive effects of dexamethasone, decreased responsiveness of the pituitary-adrenocortical system to the stimulus of insulin-induced hypoglycaemia and increased responsiveness of the system to stimulation with lysine-vasopressin. From these observations it is concluded that pituitary-dependent hyperadrenocorticism in the dog is a valid model for study of the pathogenesis of the disease in man. For the diagnosis of hyperadrenocorticism itself, the measurement of the concentration of corticosteroids in a single sample of plasma obtained 8 h after intravenous injection of 0.01 mg dexamethasone/kg was sufficient. The level of 11-hydroxycorticosteroids was less than 140 nmol/1 plasma in normal dogs, whereas higher values were found in dogs with hyperadrenocorticism. For purposes of differential diagnosis, measurement of the level of corticosteroids in the plasma both before and 4 h after intravenous injection of 0.05 mg dexamethasone/kg is adequage: suppression is obtained only in cases of pituitary-dependent hyperadrenocorticism."}
{"id": "PMID:205622", "title": "Possible role of gamma-aminobutyric acid synthesis in the mechanism of dexamethasone feedback action.", "content": "Specific inhibition of glutamic acid decarboxylase (GAD, EC 4.1.1.15; the main enzyme involved in the synthesis of gamma-aminobutyric acid) by mercaptopropionic acid interferes with the effect of dexamethasone on both the resting and stress-induced secretion of ACTH. It is postulated that dexamethasone may, at least in part, inhibit the secretion of ACTH via the induction of GAD, thereby raising the level of gamma-aminobutyric acid in the central nervous system.", "contents": "Possible role of gamma-aminobutyric acid synthesis in the mechanism of dexamethasone feedback action. Specific inhibition of glutamic acid decarboxylase (GAD, EC 4.1.1.15; the main enzyme involved in the synthesis of gamma-aminobutyric acid) by mercaptopropionic acid interferes with the effect of dexamethasone on both the resting and stress-induced secretion of ACTH. It is postulated that dexamethasone may, at least in part, inhibit the secretion of ACTH via the induction of GAD, thereby raising the level of gamma-aminobutyric acid in the central nervous system."}
{"id": "PMID:205623", "title": "Properties of rat adrenal zona reticularis cells: preparation by gravitational sedimentation.", "content": "An enriched fraction of zona reticularis cells was obtained by unit gravity sedimentation of decapsulated adrenal glands from female rats. From light microscopic and ultrastructural studies of the whole gland and the isolated cell fractions, the zona reticularis cells of the adrenal gland can be classified mainly on the bases of size, position and mitochondrial morphology. This cell population consists of two types of cell, the 'true' zoma reticularis cells (Type I, modal diameter 9 micrometer), which usually constitute 90% of the isolated reticularis fraction and 80% of the intact reticularis tissue, and cells (Type II, modal diameter 13 micrometer) with fasciculata-like properties (rich in lipid and spherical mitochondria with vesicular cristae). Staining of the cell preparation for 3beta-hydroxysteroid dehydrogenase activity also demonstrates the existence of two types of cell in the zona reticularis. The zona reticularis cell fraction, like the zona fasciculata cell fraction, was capable of producing the subsequent steroids from radioactive pregnenolone: corticosterone, deoxycorticosterone, 18-hydroxydeoxycorticosterone, 11-dehydrocorticosterone, progesterone and androstenedione. However, the pattern of steroid production differed markedly between the zona reticularis and zona fasciculata cells, particularly with respect to the production of deoxycorticosterone and corticosterone (and its correlated steroids, 11-dehydrocorticosterone and 18-hydroxydeoxycorticosterone). When R (the ratio of deoxycorticosterone : corticosterone plus 11-dehydrocorticosterone) for the purest preparation of reticularis cells was compared with R for the corresponding preparation of fasciculata cells, the normalized ratio was found to be 6.4, 16.4 and 20.1 in three experiments. The pattern of production of androstenedione per cell was similar in the reticularis and fasciculata cell fractions. The exact mechanism for the altered pattern of steroid metabolism remains to be elucidated. However, these results establish that the corticosteroids produced by the cells of the zona reticularis may be quantitatively, if not qualitatively, different from those produced by the zona fasciculata cells.", "contents": "Properties of rat adrenal zona reticularis cells: preparation by gravitational sedimentation. An enriched fraction of zona reticularis cells was obtained by unit gravity sedimentation of decapsulated adrenal glands from female rats. From light microscopic and ultrastructural studies of the whole gland and the isolated cell fractions, the zona reticularis cells of the adrenal gland can be classified mainly on the bases of size, position and mitochondrial morphology. This cell population consists of two types of cell, the 'true' zoma reticularis cells (Type I, modal diameter 9 micrometer), which usually constitute 90% of the isolated reticularis fraction and 80% of the intact reticularis tissue, and cells (Type II, modal diameter 13 micrometer) with fasciculata-like properties (rich in lipid and spherical mitochondria with vesicular cristae). Staining of the cell preparation for 3beta-hydroxysteroid dehydrogenase activity also demonstrates the existence of two types of cell in the zona reticularis. The zona reticularis cell fraction, like the zona fasciculata cell fraction, was capable of producing the subsequent steroids from radioactive pregnenolone: corticosterone, deoxycorticosterone, 18-hydroxydeoxycorticosterone, 11-dehydrocorticosterone, progesterone and androstenedione. However, the pattern of steroid production differed markedly between the zona reticularis and zona fasciculata cells, particularly with respect to the production of deoxycorticosterone and corticosterone (and its correlated steroids, 11-dehydrocorticosterone and 18-hydroxydeoxycorticosterone). When R (the ratio of deoxycorticosterone : corticosterone plus 11-dehydrocorticosterone) for the purest preparation of reticularis cells was compared with R for the corresponding preparation of fasciculata cells, the normalized ratio was found to be 6.4, 16.4 and 20.1 in three experiments. The pattern of production of androstenedione per cell was similar in the reticularis and fasciculata cell fractions. The exact mechanism for the altered pattern of steroid metabolism remains to be elucidated. However, these results establish that the corticosteroids produced by the cells of the zona reticularis may be quantitatively, if not qualitatively, different from those produced by the zona fasciculata cells."}
{"id": "PMID:205625", "title": "The effect of nalidixic acid group compounds on reduction of cytochrome c from horse heart and Candida krusei.", "content": "Reduction of cytochrome c from both horse heart and Candida krusei by FeSO4 has been demonstrated. This reaction was stimulated by nalidixic acid and structurally related compounds, and the effect was more pronounced for the yeast cytochrome. Divalent metal ions other than Fe2+ lessened or abolished the stimulation by these compounds. Fe2+ and other metal ions altered the spectra of nalidixic acid and related compounds indicating the formation of metal chelate complexes. 1,10-Phenanthroline inhibited reduction of cytochrome c b Fe2+. Other divalent metal ions relieved the inhibition, probably by forming chelates with 1,10-phenanthroline. The results suggest that metal ion chelation may be involved in the molecular mode of action of nalidixic acid and related drugs. The relevance of this artificial electron transfer system to bacterial electron transfer in vivo is discussed.", "contents": "The effect of nalidixic acid group compounds on reduction of cytochrome c from horse heart and Candida krusei. Reduction of cytochrome c from both horse heart and Candida krusei by FeSO4 has been demonstrated. This reaction was stimulated by nalidixic acid and structurally related compounds, and the effect was more pronounced for the yeast cytochrome. Divalent metal ions other than Fe2+ lessened or abolished the stimulation by these compounds. Fe2+ and other metal ions altered the spectra of nalidixic acid and related compounds indicating the formation of metal chelate complexes. 1,10-Phenanthroline inhibited reduction of cytochrome c b Fe2+. Other divalent metal ions relieved the inhibition, probably by forming chelates with 1,10-phenanthroline. The results suggest that metal ion chelation may be involved in the molecular mode of action of nalidixic acid and related drugs. The relevance of this artificial electron transfer system to bacterial electron transfer in vivo is discussed."}
{"id": "PMID:205624", "title": "Feedback synaptic interaction in the dragonfly ocellar retina.", "content": "The intracellular response of the ocellar nerve dendrite, the second order neuron in the retina of the dragonfly ocellus, has been modified by application of various drugs and a model developed to explain certain features of that response. Curare blocked the response completely. Both picrotoxin and bicuculline eliminated the \"off\" overshoot. Bicuculline also decreased the size of response and the sensitivity. gamma-Aminobutyric acid (GABA), however, increased the size of response. The evidence indicates the possibility that the receptor transmitter is acetylcholine and is inhibitory to the ocellar nerve dendrite whereas the feedback transmitter from the ocellar nerve dendrite may be GABA and is facilitory to receptor transmitter release. The model of synaptic feedback interaction developed to be consistent with these results has certain important features. It suggests that the feedback transmitter is released in the dark to increase input sensitivity from receptors in response to dim light. This implies that the dark potential of the ocellar nerve dendrite may be determined by a dynamic equilibrium established by synaptic interaction between it and the receptor terminals. Such a system is also well suited to signalling phasic information about changes in level of illumination over a wide range of intensities, a characteristic which appears to be a significant feature of the dragonfly median ocellar response.", "contents": "Feedback synaptic interaction in the dragonfly ocellar retina. The intracellular response of the ocellar nerve dendrite, the second order neuron in the retina of the dragonfly ocellus, has been modified by application of various drugs and a model developed to explain certain features of that response. Curare blocked the response completely. Both picrotoxin and bicuculline eliminated the \"off\" overshoot. Bicuculline also decreased the size of response and the sensitivity. gamma-Aminobutyric acid (GABA), however, increased the size of response. The evidence indicates the possibility that the receptor transmitter is acetylcholine and is inhibitory to the ocellar nerve dendrite whereas the feedback transmitter from the ocellar nerve dendrite may be GABA and is facilitory to receptor transmitter release. The model of synaptic feedback interaction developed to be consistent with these results has certain important features. It suggests that the feedback transmitter is released in the dark to increase input sensitivity from receptors in response to dim light. This implies that the dark potential of the ocellar nerve dendrite may be determined by a dynamic equilibrium established by synaptic interaction between it and the receptor terminals. Such a system is also well suited to signalling phasic information about changes in level of illumination over a wide range of intensities, a characteristic which appears to be a significant feature of the dragonfly median ocellar response."}
{"id": "PMID:205626", "title": "Structures of polyoma virus: on the histone component and virion core.", "content": "We have observed that purified polyoma virus is able to take up an amount of calf thymus histone equivalent to 10 to 50% of its normal histone content under conditions allowing the binding of considerably lesser amounts of several other proteins. Some of the bound histone could not be released by procedures procedures routinely used for virus purification. We have also found that some of the histone present in purified polyoma virus could be selectively released without major breakdown of virus particles. Possible models for virus structure are discussed in the light of the present and other recent data.", "contents": "Structures of polyoma virus: on the histone component and virion core. We have observed that purified polyoma virus is able to take up an amount of calf thymus histone equivalent to 10 to 50% of its normal histone content under conditions allowing the binding of considerably lesser amounts of several other proteins. Some of the bound histone could not be released by procedures procedures routinely used for virus purification. We have also found that some of the histone present in purified polyoma virus could be selectively released without major breakdown of virus particles. Possible models for virus structure are discussed in the light of the present and other recent data."}
{"id": "PMID:205628", "title": "The fate of parental herpesvirus DNA after infection with normal and photoinactivated virions.", "content": "The fate of the 3H-dT-labelled parental DNA of normal and photoinactivated herpes simplex virus type 1 (KOS strain) was followed for 8 h after infection. The sedimentation coefficients of parental virus DNA from cells infected with normal virons increased and became associated with the replicative intermediates of HSV-1 DNA. When cultured in 5-bromodeoxyuridine-containing medium, the buoyant density of the normal parental virus DNA shifted to the hybrid region (containing heavy and light molecules) of the caesium chloride density gradient. The parental virus DNA of photoinactivated virions, however, degraded quickly and did not participate in progeny virus DNA replication.", "contents": "The fate of parental herpesvirus DNA after infection with normal and photoinactivated virions. The fate of the 3H-dT-labelled parental DNA of normal and photoinactivated herpes simplex virus type 1 (KOS strain) was followed for 8 h after infection. The sedimentation coefficients of parental virus DNA from cells infected with normal virons increased and became associated with the replicative intermediates of HSV-1 DNA. When cultured in 5-bromodeoxyuridine-containing medium, the buoyant density of the normal parental virus DNA shifted to the hybrid region (containing heavy and light molecules) of the caesium chloride density gradient. The parental virus DNA of photoinactivated virions, however, degraded quickly and did not participate in progeny virus DNA replication."}
{"id": "PMID:205629", "title": "Trauma to the skin causes recurrence of herpes simplex in the mouse.", "content": "Mild trauma was induced in the skin of mice latently infected with herpes simplex virus type I by stripping the originally infected ear with cellophane tape. Recurrent herpes simplex developed at this site 2 to 5 days later. It was detected clinically by the development of erythema and vesicles and by the appearance of virus in the skin. On any one occasion about 30% of mice showed reactivated disease and increasing the severity of trauma did not increase this proportion. However the majority of animals developed reactivated disease on some occasions when stripping was repeated at monthly intervals. The results are discussed in relation to the skin trigger theory of reactivation of herpes simplex.", "contents": "Trauma to the skin causes recurrence of herpes simplex in the mouse. Mild trauma was induced in the skin of mice latently infected with herpes simplex virus type I by stripping the originally infected ear with cellophane tape. Recurrent herpes simplex developed at this site 2 to 5 days later. It was detected clinically by the development of erythema and vesicles and by the appearance of virus in the skin. On any one occasion about 30% of mice showed reactivated disease and increasing the severity of trauma did not increase this proportion. However the majority of animals developed reactivated disease on some occasions when stripping was repeated at monthly intervals. The results are discussed in relation to the skin trigger theory of reactivation of herpes simplex."}
{"id": "PMID:205630", "title": "Infection by herpes simplex virus and cells of nervous system origin: characterization of a non-permissive interaction.", "content": "Replication of herpes simplex virus type I (HSV-I) was studied in various cell lines of rat nervous system origin. Infection of neonatal rat glial primary cells with HSV-I, strain KOS, produced normal yields of progeny virus. Glioma lines B9 and B15 were permissive, the neuronal line B50 was partially restricted (10 to 100-fold reduction) and the neuronal line B103 was non-permissive (greater than 1000-fold reduction) for HSV-I (KOS) replication. Synthesis of virus DNA in infected B103 cells was not detected. However, at least some virus macromolecular synthesis was induced, including production of thymidine kinase, DNA polymerase and virus structural proteins.", "contents": "Infection by herpes simplex virus and cells of nervous system origin: characterization of a non-permissive interaction. Replication of herpes simplex virus type I (HSV-I) was studied in various cell lines of rat nervous system origin. Infection of neonatal rat glial primary cells with HSV-I, strain KOS, produced normal yields of progeny virus. Glioma lines B9 and B15 were permissive, the neuronal line B50 was partially restricted (10 to 100-fold reduction) and the neuronal line B103 was non-permissive (greater than 1000-fold reduction) for HSV-I (KOS) replication. Synthesis of virus DNA in infected B103 cells was not detected. However, at least some virus macromolecular synthesis was induced, including production of thymidine kinase, DNA polymerase and virus structural proteins."}
{"id": "PMID:205631", "title": "Cyclic excretion of hepatitis A virus in experimentally infected chimpanzees: biophysical characterization of the associated HAV particles.", "content": "Experimental infection of two chimpanzees with the Phoenix Antigen strain of HAV resulted in the cyclic excretion of virus particles on days 9-11, 14-15, and 20-21 postinoculation. Isopycnic banding in CsCl of stool suspensions prepared from 9-11; 14-15; and 17, 19, 21 dav stool pools revealed multiple buoyant densities for the associated HAV particles. Hollow HAV particles found in the 9-11 day pool banded primarily at a buoyant density of 1.30 g/cm3. HAV in the 14-15 day stool banded bimodally in a CsCl gradient, with antigen peaks at buoyant densities of 1.29 and 1.33 g/cm3. HAV in the days 17, 19, 21 stool pool also banded bimodally in a CsCl gradient; however, the antigen peaks occurred at buoyant densities of 1.33 and 1.40 g/cm3.", "contents": "Cyclic excretion of hepatitis A virus in experimentally infected chimpanzees: biophysical characterization of the associated HAV particles. Experimental infection of two chimpanzees with the Phoenix Antigen strain of HAV resulted in the cyclic excretion of virus particles on days 9-11, 14-15, and 20-21 postinoculation. Isopycnic banding in CsCl of stool suspensions prepared from 9-11; 14-15; and 17, 19, 21 dav stool pools revealed multiple buoyant densities for the associated HAV particles. Hollow HAV particles found in the 9-11 day pool banded primarily at a buoyant density of 1.30 g/cm3. HAV in the 14-15 day stool banded bimodally in a CsCl gradient, with antigen peaks at buoyant densities of 1.29 and 1.33 g/cm3. HAV in the days 17, 19, 21 stool pool also banded bimodally in a CsCl gradient; however, the antigen peaks occurred at buoyant densities of 1.33 and 1.40 g/cm3."}
{"id": "PMID:205632", "title": "The virion and soluble antigen proteins of variola, monkeypox, and vaccinia viruses.", "content": "The structural proteins in purified preparations of variola, monkeypox, and vaccinia viruses were separated and compared by using a high resolution SDS-polyacrylamide gel electrophoresis system. About 30 proteins were resolved for each virus by autoradiography of longitudinally-sliced gel rods. Although the autoradioelectropherograms of each virus were similar, it was possible to differentiate them by their unique protein pattern in the 30,000 to 40,000 molecular weight region of the gels. A single virion glycoprotein (mol. wt. = 38 X 10(3)) and a virion phosphoprotein (mol. wt. = 12 X 10(3)) were associated with each of the virus preparations. Cross-absorbed monospecific immune sera against variola, monkeypox, and vaccinia virus-infected cells were used in immunodiffusion tests to precipitate radiolabeled, homologous, soluble antigen proteins. The predominant antigen protein associated with each immunospecific precipitate had a molecular weight of approximately 73,000.", "contents": "The virion and soluble antigen proteins of variola, monkeypox, and vaccinia viruses. The structural proteins in purified preparations of variola, monkeypox, and vaccinia viruses were separated and compared by using a high resolution SDS-polyacrylamide gel electrophoresis system. About 30 proteins were resolved for each virus by autoradiography of longitudinally-sliced gel rods. Although the autoradioelectropherograms of each virus were similar, it was possible to differentiate them by their unique protein pattern in the 30,000 to 40,000 molecular weight region of the gels. A single virion glycoprotein (mol. wt. = 38 X 10(3)) and a virion phosphoprotein (mol. wt. = 12 X 10(3)) were associated with each of the virus preparations. Cross-absorbed monospecific immune sera against variola, monkeypox, and vaccinia virus-infected cells were used in immunodiffusion tests to precipitate radiolabeled, homologous, soluble antigen proteins. The predominant antigen protein associated with each immunospecific precipitate had a molecular weight of approximately 73,000."}
{"id": "PMID:205633", "title": "Residual effects of ethanol and chlordiazepoxide treatments for alcohol withdrawal.", "content": "Eighteen male alcoholics were randomly assigned to one of two alcohol detoxification treatments. One group received a low dose ethanol treatment while the other group received a chlordiazepoxide treatment. This study compares recovery of sleep EEG and clinical symptomatology following these two detoxification treatments. Sleep EEG and clinical measures were obtained for the final medication day and during a 6-day postmedication \"recovery\" period. The chlordiazepoxide treatment produced suppression of rapid eye movement (REM) sleep lasting for about 4 days and virtually eliminated delta sleep (stages III and IV) during the recovery period. The low dose ethanol treatment regimen produced less disruption of REM and delta sleep during the recovery period. These findings suggest that under some circumstances an ethanol treatment regimen may prove more beneficial to the healthy alcoholic patient than current regimens which employ other psychoactive medication. In particular, the long lasting suppression of delta sleep during the recovery period in subjects treated with chlordiazepoxide suggests a vulnerability of the slow wave sleep mechanisms during early alcohol abstinence and raises the possibility that this regimen prolongs functional tolerance to alcohol effects. Continued clinical evaluation of low dose ethanol detoxification treatment is suggested.", "contents": "Residual effects of ethanol and chlordiazepoxide treatments for alcohol withdrawal. Eighteen male alcoholics were randomly assigned to one of two alcohol detoxification treatments. One group received a low dose ethanol treatment while the other group received a chlordiazepoxide treatment. This study compares recovery of sleep EEG and clinical symptomatology following these two detoxification treatments. Sleep EEG and clinical measures were obtained for the final medication day and during a 6-day postmedication \"recovery\" period. The chlordiazepoxide treatment produced suppression of rapid eye movement (REM) sleep lasting for about 4 days and virtually eliminated delta sleep (stages III and IV) during the recovery period. The low dose ethanol treatment regimen produced less disruption of REM and delta sleep during the recovery period. These findings suggest that under some circumstances an ethanol treatment regimen may prove more beneficial to the healthy alcoholic patient than current regimens which employ other psychoactive medication. In particular, the long lasting suppression of delta sleep during the recovery period in subjects treated with chlordiazepoxide suggests a vulnerability of the slow wave sleep mechanisms during early alcohol abstinence and raises the possibility that this regimen prolongs functional tolerance to alcohol effects. Continued clinical evaluation of low dose ethanol detoxification treatment is suggested."}
{"id": "PMID:205634", "title": "Vertebral and epidural hemangioma with paraplegia in Klippel-Trenaunay-Weber syndrome. Case report.", "content": "A patient with a rare case of Klippel-Trenaunay-Weber syndrome presented with paraplegia due to compression by a vertebral and epidural cavernous hemangioma. The metameric distribution of the large cutaneous vascular nevus provided the clinical clue to the nature of the spinal lesion. The association of the two lesions is explained in the basis of developmental anomaly.", "contents": "Vertebral and epidural hemangioma with paraplegia in Klippel-Trenaunay-Weber syndrome. Case report. A patient with a rare case of Klippel-Trenaunay-Weber syndrome presented with paraplegia due to compression by a vertebral and epidural cavernous hemangioma. The metameric distribution of the large cutaneous vascular nevus provided the clinical clue to the nature of the spinal lesion. The association of the two lesions is explained in the basis of developmental anomaly."}
{"id": "PMID:205635", "title": "Ga-67 citrate imaging in tumors of the genito-urinary tract: report of cooperative study.", "content": "Whole-body imaging with Ga-67 citrate in 127 tumors of the genito-urinary tract has been evaluated by a cooperative group using a uniform protocol. Primary sites of tumor were not detectable by imaging, except for one bladder and one kidney tumor. Proven and apparent metastases yielded positive scans, however, in 51% of prostatic, 50% of bladder, 72% of kidney, and 53% of testicular neoplasms. In bladder and kidneys metastases, if bone sites are excluded, detection of soft tissue metastases was 61% and 75%, respectively. In embryonal-cell carcinoma of the testicle, 74% of metastatic foci were detected.", "contents": "Ga-67 citrate imaging in tumors of the genito-urinary tract: report of cooperative study. Whole-body imaging with Ga-67 citrate in 127 tumors of the genito-urinary tract has been evaluated by a cooperative group using a uniform protocol. Primary sites of tumor were not detectable by imaging, except for one bladder and one kidney tumor. Proven and apparent metastases yielded positive scans, however, in 51% of prostatic, 50% of bladder, 72% of kidney, and 53% of testicular neoplasms. In bladder and kidneys metastases, if bone sites are excluded, detection of soft tissue metastases was 61% and 75%, respectively. In embryonal-cell carcinoma of the testicle, 74% of metastatic foci were detected."}
{"id": "PMID:205636", "title": "Factors influencing paper chromatographic analysis of technetium-99m phosphorus compounds: concise communication.", "content": "A single-paper chromatographic system has been developed, capable of resolving Tc-99m dioxide, [99mTc] pertechnetate and Tc-99m phosphorus compounds. The best separations are obtained with CM82 paper developed in 0.5 m naCl, and 3MM or ashless No. 40 paper developed in 1 M sodium acetate buffer. In these systems, 99TcO2 remains at the origin, while 99mTcO4--and Tc-99m phosphorus compounds move with Rf values of 0.56--0.75 and 0.80--1.0, respectively.", "contents": "Factors influencing paper chromatographic analysis of technetium-99m phosphorus compounds: concise communication. A single-paper chromatographic system has been developed, capable of resolving Tc-99m dioxide, [99mTc] pertechnetate and Tc-99m phosphorus compounds. The best separations are obtained with CM82 paper developed in 0.5 m naCl, and 3MM or ashless No. 40 paper developed in 1 M sodium acetate buffer. In these systems, 99TcO2 remains at the origin, while 99mTcO4--and Tc-99m phosphorus compounds move with Rf values of 0.56--0.75 and 0.80--1.0, respectively."}
{"id": "PMID:205639", "title": "Stimulation of lead absorption by vitamin D administration.", "content": "Two methods for the determination of lead absorption have been developed using the rat as the test animal. One is an everted intestinal sac method in which the time course of 210Pb transport across intestinal wall can be followed in vitro; and the other, 210Pb absorption from the intestine following gastric intubation can be followed in vivo. By using these techniques it can be clearly demonstrated that vitamin D markedly enhances lead absorption. Both techniques provide evidence that the distal small intestine is the major site of lead absorption and the site of greatest vitamin D stimulation. Lead acetate is apparently absorbed to the extent of 45% as it passes through the small intestine at a concentration of 0.01 mM.", "contents": "Stimulation of lead absorption by vitamin D administration. Two methods for the determination of lead absorption have been developed using the rat as the test animal. One is an everted intestinal sac method in which the time course of 210Pb transport across intestinal wall can be followed in vitro; and the other, 210Pb absorption from the intestine following gastric intubation can be followed in vivo. By using these techniques it can be clearly demonstrated that vitamin D markedly enhances lead absorption. Both techniques provide evidence that the distal small intestine is the major site of lead absorption and the site of greatest vitamin D stimulation. Lead acetate is apparently absorbed to the extent of 45% as it passes through the small intestine at a concentration of 0.01 mM."}
{"id": "PMID:205640", "title": "Adenoid cystic carcinoma of the parotid gland: report of case.", "content": "A case of adenoid cystic carcinoma of the parotid gland is reported, in which the initial symptom was facial paresthesia. Pathologic features, treatment, and prognosis of the tumor have been discussed.", "contents": "Adenoid cystic carcinoma of the parotid gland: report of case. A case of adenoid cystic carcinoma of the parotid gland is reported, in which the initial symptom was facial paresthesia. Pathologic features, treatment, and prognosis of the tumor have been discussed."}
{"id": "PMID:205641", "title": "Malignant mixed tumor of the soft palate.", "content": "Malignant mixed tumor (carcinoma within a pleomorphic adenoma) is an unusual tumor that rarely occurs in the minor salivary glands of the soft palate. We have reported a cases and a review of the terminology, diagnosis, and treatment.", "contents": "Malignant mixed tumor of the soft palate. Malignant mixed tumor (carcinoma within a pleomorphic adenoma) is an unusual tumor that rarely occurs in the minor salivary glands of the soft palate. We have reported a cases and a review of the terminology, diagnosis, and treatment."}
{"id": "PMID:205643", "title": "Antibody response to live virus vaccines in congenital and neonatal cytomegalovirus infections.", "content": "When 42 infants with congenitally or neonatally acquired cytomegalovirus infections were one year of age, they were given live attenuated measles-mumps-rubella combined vaccine to determine what effect, if any, the existence of chronic CMV infection has on the antibody response to measles and rubella antigens. When the infected infants were compared with 60 healthy non-CMV-infected control infants, no significant difference in the seroconversion rates or ultimate antibody levels was observed with either measles or rubella antigens. Persistence of antibody, when measured three years after vaccination, was likewise similar in each group; levels had waned only slightly. These results demonstrate the intactness of humoral immunity in children with pre- and perinatal CMV infection.", "contents": "Antibody response to live virus vaccines in congenital and neonatal cytomegalovirus infections. When 42 infants with congenitally or neonatally acquired cytomegalovirus infections were one year of age, they were given live attenuated measles-mumps-rubella combined vaccine to determine what effect, if any, the existence of chronic CMV infection has on the antibody response to measles and rubella antigens. When the infected infants were compared with 60 healthy non-CMV-infected control infants, no significant difference in the seroconversion rates or ultimate antibody levels was observed with either measles or rubella antigens. Persistence of antibody, when measured three years after vaccination, was likewise similar in each group; levels had waned only slightly. These results demonstrate the intactness of humoral immunity in children with pre- and perinatal CMV infection."}
{"id": "PMID:205644", "title": "Sexual precocity in association with septo-optic dysplasia and hypothalamic hypopituitarism.", "content": "Sexual precocity in association with abnormalities of the central nervous system is well known, but its occurrence with hypothalamic hypopituitarism is most unusual. We report five females with septo-optic dysplasia, blindness, and multiple pituitary tropic hormone deficiencies: all were growth hormone and adrenocorticotropic hormone deficient; two had diabetes insipidus; one had sexual precocity, and one had early pubertal maturation, whereas three were prepubertal and responded to administration of synthetic gonadotropin-releasing hormone. These children retained ability to secrete gonadotropins despite the presence of anterior hypothalamic disease. Experimental data from primates plus our observations on these patients raise questions about the role of the anterior hypothalamus in gonadotropin secretion in man.", "contents": "Sexual precocity in association with septo-optic dysplasia and hypothalamic hypopituitarism. Sexual precocity in association with abnormalities of the central nervous system is well known, but its occurrence with hypothalamic hypopituitarism is most unusual. We report five females with septo-optic dysplasia, blindness, and multiple pituitary tropic hormone deficiencies: all were growth hormone and adrenocorticotropic hormone deficient; two had diabetes insipidus; one had sexual precocity, and one had early pubertal maturation, whereas three were prepubertal and responded to administration of synthetic gonadotropin-releasing hormone. These children retained ability to secrete gonadotropins despite the presence of anterior hypothalamic disease. Experimental data from primates plus our observations on these patients raise questions about the role of the anterior hypothalamus in gonadotropin secretion in man."}
{"id": "PMID:205646", "title": "Synthesis of as-triazines as potential antiviral agents.", "content": "Four acenaphtho[1,2-e]-as-triazines and 11 5,6-diaryl-as-triazines, all substituted with an aliphatic or aromatic amino function in the 3-position, were synthesized. Two acenaphthotriazines were active against vesicular stomatitis virus in tissue culture.", "contents": "Synthesis of as-triazines as potential antiviral agents. Four acenaphtho[1,2-e]-as-triazines and 11 5,6-diaryl-as-triazines, all substituted with an aliphatic or aromatic amino function in the 3-position, were synthesized. Two acenaphthotriazines were active against vesicular stomatitis virus in tissue culture."}
{"id": "PMID:205647", "title": "Neostigmine-induced alterations at the mammalian neuromuscular junction. I. Muscle contraction and electrophysiology.", "content": "The effects of single and repetitive injections of neostigmine on neuromuscular physiology were examined in rat extensor digitorum longus muscles. The characteristic facilitation of neuromuscular transmission associated with acute anticholinesterase treatment was accompanied by significant pre- and postsynaptic alterations in neuromuscular transmission. Three days of neostigmine treatment caused a decrease in indirectly and directly elicited muscle contraction. Miniature end-plate potential amplitude and frequency, end-plate potential amplitude, junctional acetylcholine sensitivity and quantal content of nerve-evoked end-plate potentials were also decreased by this treatment. By 22 to 25 days of continued treatment, the decreased rate of transmitter release had returned almost to normal, whereas the alterations of the postsynaptic membrane persisted for as long as 106 days. Alterations were also found in the muscle action potential and in certain passive electrical properties of the extrajunctional muscle membrane. In addition, many of the physiological changes were correlated directly with the morphological changes observed in rats treated similarly. We conclude that neostigmine treatment in rats in therapeutic doses has deleterious effects on neuromuscular physiology and neuromuscular ultrastructure. Although the pattern of these changes is not identical with that seen in rabbit and human myasthenia gravis, the neostigmine treatment used in patients with myasthenia gravis may contribute in part to the neuromuscular alterations observed in this disease.", "contents": "Neostigmine-induced alterations at the mammalian neuromuscular junction. I. Muscle contraction and electrophysiology. The effects of single and repetitive injections of neostigmine on neuromuscular physiology were examined in rat extensor digitorum longus muscles. The characteristic facilitation of neuromuscular transmission associated with acute anticholinesterase treatment was accompanied by significant pre- and postsynaptic alterations in neuromuscular transmission. Three days of neostigmine treatment caused a decrease in indirectly and directly elicited muscle contraction. Miniature end-plate potential amplitude and frequency, end-plate potential amplitude, junctional acetylcholine sensitivity and quantal content of nerve-evoked end-plate potentials were also decreased by this treatment. By 22 to 25 days of continued treatment, the decreased rate of transmitter release had returned almost to normal, whereas the alterations of the postsynaptic membrane persisted for as long as 106 days. Alterations were also found in the muscle action potential and in certain passive electrical properties of the extrajunctional muscle membrane. In addition, many of the physiological changes were correlated directly with the morphological changes observed in rats treated similarly. We conclude that neostigmine treatment in rats in therapeutic doses has deleterious effects on neuromuscular physiology and neuromuscular ultrastructure. Although the pattern of these changes is not identical with that seen in rabbit and human myasthenia gravis, the neostigmine treatment used in patients with myasthenia gravis may contribute in part to the neuromuscular alterations observed in this disease."}
{"id": "PMID:205648", "title": "Pathosis of the hard and soft palate.", "content": "In this article a few of the more recently emphasized and pertinent conditions that may affect the hard and soft palate have been discussed. The purpose of the article is not to present in all-inclusive classification of lesions occurring the palate. Disease of the palate may be local in nature or may reflect a systemic condition. Dentists must be conscious of the palate as the site of many possible pathoses. The prosthodontist in particular must observe and carefully evaluate the palate and insure its good health before he can prescribe a prosthesis to cover it. Dentistry provides a health service which affects the entire human organism and not just the oral cavity. Therefore an understanding of the varied nature of pathosis as it relates to the oral cavity, and especially the palate, is essential. Continuous surveillance of the palatal regions insures that the dentist's obligation to detect oral abnormalities in patients is in large measure fulfilled.", "contents": "Pathosis of the hard and soft palate. In this article a few of the more recently emphasized and pertinent conditions that may affect the hard and soft palate have been discussed. The purpose of the article is not to present in all-inclusive classification of lesions occurring the palate. Disease of the palate may be local in nature or may reflect a systemic condition. Dentists must be conscious of the palate as the site of many possible pathoses. The prosthodontist in particular must observe and carefully evaluate the palate and insure its good health before he can prescribe a prosthesis to cover it. Dentistry provides a health service which affects the entire human organism and not just the oral cavity. Therefore an understanding of the varied nature of pathosis as it relates to the oral cavity, and especially the palate, is essential. Continuous surveillance of the palatal regions insures that the dentist's obligation to detect oral abnormalities in patients is in large measure fulfilled."}
{"id": "PMID:205650", "title": "Presence of leucocyte inclusions in spleen and bone marrow of patients with Felty's syndrome.", "content": "The spleens from two patients with Felty's syndrome and the bone marrow from one patient with Felty's syndrome were examined for the presence of intracytoplasmic inclusions in neutrophils when stained with antibodies to IgG, IgM, IgA, and betalc. Four normal spleens from trauma patients were similarly examined. In both spleens and the bone marrow from the Felty patients, large inclusions were noted. In none of the four normal spleens were large inclusions present. These studies suggest that phagocytosis of immune complexes by neutrophils in Felty patients may induce sequestration of these cells in the spleen and bone marrow.", "contents": "Presence of leucocyte inclusions in spleen and bone marrow of patients with Felty's syndrome. The spleens from two patients with Felty's syndrome and the bone marrow from one patient with Felty's syndrome were examined for the presence of intracytoplasmic inclusions in neutrophils when stained with antibodies to IgG, IgM, IgA, and betalc. Four normal spleens from trauma patients were similarly examined. In both spleens and the bone marrow from the Felty patients, large inclusions were noted. In none of the four normal spleens were large inclusions present. These studies suggest that phagocytosis of immune complexes by neutrophils in Felty patients may induce sequestration of these cells in the spleen and bone marrow."}
{"id": "PMID:205660", "title": "Characterization of the inhibitory effects of retinoids on the in vitro growth of two malignant murine melanomas.", "content": "The in vitro proliferation of murine melanoma cell lines S91 and B16 was inhibited by retinoic acid and retinyl acetate. The inhibitory effects were dependent on retinoid concentration and increased from 55 and 30% at 10(-9) M retinoic acid to 85 and 82% at 10(-5) M retinoic acid for S91 and B16 melanoma cells, respectively. S91 melanoma cells were more sensitive than B16 melanoma cells to inhibition by either retinoid, and both cell lines were more sensitive to retinoic acid than to retinyl acetate. When exposed to 10(-5) M retinoic acid, the two cell types grew at the same rate as did control cells for 48 hours, whereupon the growth rates of retinoid-treated cells decreased. After 6 days, the number of cells in control cultures increased 140 times (S91 melanoma cells) and 265 times (B16 melanoma cells), whereas retinoic acid-treated cells increased only 14 times (S91 melanoma cells) and 40 times (B16 melanoma cells). The degree of growth inhibition by retinoic acid was not dependent on initial cell density. Cortisone and hydrocortisone failed to prevent or reduce the inhibitory effect of retinoic acid; the release of lysosomal acid phosphatase was not increased and the intracellular level of 3',5'-cyclic AMP in cells grown for 5 days in the presence of 10(-5) M retinoic acid was not elevated. Viability of S91 and B16 cells after 8 days' exposure to 10(-5) M retinoic acid was similar to that in control cultures. The reduced growth rate of retinoic acid-treated cells reversed to the control rate 48-72 hours after removal of retinoic acid from the growth medium.", "contents": "Characterization of the inhibitory effects of retinoids on the in vitro growth of two malignant murine melanomas. The in vitro proliferation of murine melanoma cell lines S91 and B16 was inhibited by retinoic acid and retinyl acetate. The inhibitory effects were dependent on retinoid concentration and increased from 55 and 30% at 10(-9) M retinoic acid to 85 and 82% at 10(-5) M retinoic acid for S91 and B16 melanoma cells, respectively. S91 melanoma cells were more sensitive than B16 melanoma cells to inhibition by either retinoid, and both cell lines were more sensitive to retinoic acid than to retinyl acetate. When exposed to 10(-5) M retinoic acid, the two cell types grew at the same rate as did control cells for 48 hours, whereupon the growth rates of retinoid-treated cells decreased. After 6 days, the number of cells in control cultures increased 140 times (S91 melanoma cells) and 265 times (B16 melanoma cells), whereas retinoic acid-treated cells increased only 14 times (S91 melanoma cells) and 40 times (B16 melanoma cells). The degree of growth inhibition by retinoic acid was not dependent on initial cell density. Cortisone and hydrocortisone failed to prevent or reduce the inhibitory effect of retinoic acid; the release of lysosomal acid phosphatase was not increased and the intracellular level of 3',5'-cyclic AMP in cells grown for 5 days in the presence of 10(-5) M retinoic acid was not elevated. Viability of S91 and B16 cells after 8 days' exposure to 10(-5) M retinoic acid was similar to that in control cultures. The reduced growth rate of retinoic acid-treated cells reversed to the control rate 48-72 hours after removal of retinoic acid from the growth medium."}
{"id": "PMID:205661", "title": "Enhancement of the tumorigenicity of preneoplastic mammary nodule lines by enzymatic dissociation.", "content": "Preneoplastic mammary nodule lines D1, D2, and C4 were enzymatically dissociated with collagenase, hyaluronidase, and pronase or with only collagenase and hyaluronidase to produce high yields of viable single cells; 10(5) cells were injected into the cleared mammary fat pads of syngeneic BALB/cCrgl mice. In 11 experiments involving three different preneoplastic nodule lines with different tumor potentials, all dissociated nodule cell lines showed a marked increase in tumorigenicity as compared to the same tissues transplanted as 1-mm3 pieces. The results could not be explained on the basis of differences between the amounts of cells transplanted in the two procedures. In a second series of experiments, normal mammary cells from virgin, pregnant, or lactating mice were mixed in different ratios with 10(5) nodule cells and injected into the mammary fat pads. The presence of normal cells reversed the marked increase in the tumorigenicity of enzymatically dissociated nodule cells to a level equal to or less than the tumorigenicity of control transplants (1-mm3 pieces). The growth of 10(5) mammary tumor cells was not inhibited when tumor cells were mixed with 3 x 10(5) normal cells and transplanted into the mammary fat pads. These results showed that enzymatic dissociation can lead to an increase in tumor potential of preneoplastic mammary nodule lines, and they supported the hypothesis that nodule cells, but not neoplastic cells, are sensitive to the growth-inhibitory effects of normal mammary cells.", "contents": "Enhancement of the tumorigenicity of preneoplastic mammary nodule lines by enzymatic dissociation. Preneoplastic mammary nodule lines D1, D2, and C4 were enzymatically dissociated with collagenase, hyaluronidase, and pronase or with only collagenase and hyaluronidase to produce high yields of viable single cells; 10(5) cells were injected into the cleared mammary fat pads of syngeneic BALB/cCrgl mice. In 11 experiments involving three different preneoplastic nodule lines with different tumor potentials, all dissociated nodule cell lines showed a marked increase in tumorigenicity as compared to the same tissues transplanted as 1-mm3 pieces. The results could not be explained on the basis of differences between the amounts of cells transplanted in the two procedures. In a second series of experiments, normal mammary cells from virgin, pregnant, or lactating mice were mixed in different ratios with 10(5) nodule cells and injected into the mammary fat pads. The presence of normal cells reversed the marked increase in the tumorigenicity of enzymatically dissociated nodule cells to a level equal to or less than the tumorigenicity of control transplants (1-mm3 pieces). The growth of 10(5) mammary tumor cells was not inhibited when tumor cells were mixed with 3 x 10(5) normal cells and transplanted into the mammary fat pads. These results showed that enzymatic dissociation can lead to an increase in tumor potential of preneoplastic mammary nodule lines, and they supported the hypothesis that nodule cells, but not neoplastic cells, are sensitive to the growth-inhibitory effects of normal mammary cells."}
{"id": "PMID:205662", "title": "Carcinogenicity and acute toxicity of dimethylnitrosamine in rainbow trout (Salmo gairdneri).", "content": "Four-week-old rainbow trout (Salmo gairdneri) were fed diets containing 0, 3, 50, 200, 400, and 800 ppm dimethylnitrosamine (DMN) for 52 weeks. At the end of 52 weeks, the fish were fed a control diet without DMN for an additional 26 weeks. Samples were taken at 26, 52, and 78 weeks to determine tumor incidence. A dose-related carcinogenic response was established from these results, and an equation was derived to relate the level of the carcinogen to the hepatocellular carcinoma incidence. From a published dose-response study that used outbred Porton rats, a second equation was derived for comparison. Rats and trout were approximately equal in their sensitivity to DMN carcinogenesis. The median lethal dose after ip injection of DMN was 1,770 mg/kg body weight in rainbow trout. Relative to the range of 15-50 mg/kg body weight reported for several mammalian species, trout were resistant to the acute toxicity of DMN.", "contents": "Carcinogenicity and acute toxicity of dimethylnitrosamine in rainbow trout (Salmo gairdneri). Four-week-old rainbow trout (Salmo gairdneri) were fed diets containing 0, 3, 50, 200, 400, and 800 ppm dimethylnitrosamine (DMN) for 52 weeks. At the end of 52 weeks, the fish were fed a control diet without DMN for an additional 26 weeks. Samples were taken at 26, 52, and 78 weeks to determine tumor incidence. A dose-related carcinogenic response was established from these results, and an equation was derived to relate the level of the carcinogen to the hepatocellular carcinoma incidence. From a published dose-response study that used outbred Porton rats, a second equation was derived for comparison. Rats and trout were approximately equal in their sensitivity to DMN carcinogenesis. The median lethal dose after ip injection of DMN was 1,770 mg/kg body weight in rainbow trout. Relative to the range of 15-50 mg/kg body weight reported for several mammalian species, trout were resistant to the acute toxicity of DMN."}
{"id": "PMID:205663", "title": "Aflatoxin B1 induction of hepatocellular carcinoma in the embryos of rainbow trout (Salmo gairdneri).", "content": "Liver cancer in rainbow trout was induced by exposure of fertile eggs to an aqueous, 0.5 ppm (microgram/ml) solution of aflatoxin B1 (AFB1) for 1 hour. Single treatments, given on alternate days during the embryonic period, produced a low cancer incidence (less than 20%) prior to formation of the embryonic liver on day 14, but a steadily increasing incidence from day 15 (31.7%) until day 23 (58.3%), in fish examined 1 year later. Treatment of trout eggs with [14C]AFB1 was used to quantitate the amount of AFB1 absorbed by the eggs. Twenty-one-day-old rainbow trout eggs absorbed approximately 30 ng of [14C]AFB1 during a 1-hour exposure to 0.5 ppm aqueous [14C]AFB1. After 1 day 85-90% of the [14C]AFB1 was either metabolized and excreted or leached from the egg. The residual [14C]AFB1 remained constant until hatching when an additional 50% was lost. Comparison of the amount of AFB1 absorbed by eggs with the amount of AFB1 consumed per fish during a 1-year feeding trial at 4 ppb in the diet indicates that the trout embryo is even more sensitive than juvenile trout to the carcinogenic properties of AFB1.", "contents": "Aflatoxin B1 induction of hepatocellular carcinoma in the embryos of rainbow trout (Salmo gairdneri). Liver cancer in rainbow trout was induced by exposure of fertile eggs to an aqueous, 0.5 ppm (microgram/ml) solution of aflatoxin B1 (AFB1) for 1 hour. Single treatments, given on alternate days during the embryonic period, produced a low cancer incidence (less than 20%) prior to formation of the embryonic liver on day 14, but a steadily increasing incidence from day 15 (31.7%) until day 23 (58.3%), in fish examined 1 year later. Treatment of trout eggs with [14C]AFB1 was used to quantitate the amount of AFB1 absorbed by the eggs. Twenty-one-day-old rainbow trout eggs absorbed approximately 30 ng of [14C]AFB1 during a 1-hour exposure to 0.5 ppm aqueous [14C]AFB1. After 1 day 85-90% of the [14C]AFB1 was either metabolized and excreted or leached from the egg. The residual [14C]AFB1 remained constant until hatching when an additional 50% was lost. Comparison of the amount of AFB1 absorbed by eggs with the amount of AFB1 consumed per fish during a 1-year feeding trial at 4 ppb in the diet indicates that the trout embryo is even more sensitive than juvenile trout to the carcinogenic properties of AFB1."}
{"id": "PMID:205664", "title": "Cyclic adenosine 3',5'-monophosphate-binding protein: role in ovariectomy-induced regression of a hormone-dependent mammary tumor in Sprague-Dawley female rats.", "content": "Cyclic AMP- and estrogen-binding activities were present in 7,12-dimethylbenz[a]anthracene-induced mammary carcinomas in Sprague-Dawley female rats. Soon after ovariectomy of the host, cyclic AMP binding markedly increased and estrogen binding decreased in regressing tumors. These changes were reversed when tumor growth was resumed following the injection of estradiol-17beta. The data suggested the possible involvement of cyclic AMP binding in the growth control of a hormone-dependent mammary tumor.", "contents": "Cyclic adenosine 3',5'-monophosphate-binding protein: role in ovariectomy-induced regression of a hormone-dependent mammary tumor in Sprague-Dawley female rats. Cyclic AMP- and estrogen-binding activities were present in 7,12-dimethylbenz[a]anthracene-induced mammary carcinomas in Sprague-Dawley female rats. Soon after ovariectomy of the host, cyclic AMP binding markedly increased and estrogen binding decreased in regressing tumors. These changes were reversed when tumor growth was resumed following the injection of estradiol-17beta. The data suggested the possible involvement of cyclic AMP binding in the growth control of a hormone-dependent mammary tumor."}
{"id": "PMID:205666", "title": "State of Epstein-Barr virus DNA in an American Burkitt's lymphoma line.", "content": "A human lymphoma cell line, positive for the Epstein-Barr virus (EBV)-associated nuclear antigen, was recently established from a North American Burkitt's lymphoma. This cell line, SU-AmB-2, contained EBV DNA both in the form of circular, nonintegrated DNA molecules of viral genome length, present in multiple copies per cell, and as integrated sequences. Having DNA present in both of these forms, it resembled cell lines established from African Burkitt's lymphomas. In studies on EBV strain differences, the episomal viral DNA in Burkitt's lymphoma cells may now be compared with viral DNA in nonmalignant cells with the use of cell lines from Burkitt's lymphoma patients of similar geographic origin.", "contents": "State of Epstein-Barr virus DNA in an American Burkitt's lymphoma line. A human lymphoma cell line, positive for the Epstein-Barr virus (EBV)-associated nuclear antigen, was recently established from a North American Burkitt's lymphoma. This cell line, SU-AmB-2, contained EBV DNA both in the form of circular, nonintegrated DNA molecules of viral genome length, present in multiple copies per cell, and as integrated sequences. Having DNA present in both of these forms, it resembled cell lines established from African Burkitt's lymphomas. In studies on EBV strain differences, the episomal viral DNA in Burkitt's lymphoma cells may now be compared with viral DNA in nonmalignant cells with the use of cell lines from Burkitt's lymphoma patients of similar geographic origin."}
{"id": "PMID:205667", "title": "Leukemogenic activity of thymotropic, ecotropic, and xenotropic radiation leukemia virus isolates.", "content": "Thymotropic, ecotropic, and xenotropic oncoviruses were isolated from the C57BL/6 mouse radiation leukemia system and were propagated in culture. The purified viruses were inoculated singly and in various combinations into groups of mice, and leukemia incidence was determined. Only the thymotropic virus was leukemogenic in vivo.", "contents": "Leukemogenic activity of thymotropic, ecotropic, and xenotropic radiation leukemia virus isolates. Thymotropic, ecotropic, and xenotropic oncoviruses were isolated from the C57BL/6 mouse radiation leukemia system and were propagated in culture. The purified viruses were inoculated singly and in various combinations into groups of mice, and leukemia incidence was determined. Only the thymotropic virus was leukemogenic in vivo."}
{"id": "PMID:205668", "title": "Integrated viral DNA sequences in Epstein-Barr virus-converted human lymphoma lines.", "content": "Most human lymphoid cell lines contain multiple copies of circular, nonintegrated Epstein-Barr virus (EBV) DNA molecules as well as viral DNA sequences with properties of integrated DNA. The physical state of the EBV DNA in a human lymphoma line that only contains one virus genome equivalent per cell has now been studied by three different methods, neutral CsCl density gradient centrifugation, actinomycin D-CsCl gradient centrifugation, and Hirt fractionation. This cell line, AW-Ramos, has been obtained by EBV infection in vitro of the apparently EBV-negative Ramos lymphoma line. The results indicate that the EBV DNA in AW-Ramos is present exclusively in a linearly integrated form. Similar data were obtained with two other EBV-converted sublines of Ramos cells.", "contents": "Integrated viral DNA sequences in Epstein-Barr virus-converted human lymphoma lines. Most human lymphoid cell lines contain multiple copies of circular, nonintegrated Epstein-Barr virus (EBV) DNA molecules as well as viral DNA sequences with properties of integrated DNA. The physical state of the EBV DNA in a human lymphoma line that only contains one virus genome equivalent per cell has now been studied by three different methods, neutral CsCl density gradient centrifugation, actinomycin D-CsCl gradient centrifugation, and Hirt fractionation. This cell line, AW-Ramos, has been obtained by EBV infection in vitro of the apparently EBV-negative Ramos lymphoma line. The results indicate that the EBV DNA in AW-Ramos is present exclusively in a linearly integrated form. Similar data were obtained with two other EBV-converted sublines of Ramos cells."}
{"id": "PMID:205669", "title": "Polyoma virus-specific RNA synthesis in an inducible line of polyoma virus-transformed rat cells.", "content": "Viral RNA present in the inducible LPT clone 1A of polyoma virus-transformed rat cells was characterized before and after mitomycin C induction by hybridization with 32P-labeled separated E and L strands of polyoma viral DNA restriction endonuclease fragments. In clone 1A cells maintained under normal growth conditions, the cytoplasm contained a transcript of the E-strand DNA from the \"early\" region similar to that previously identified in lytically infected cells, as well as minor quantities of RNA complementary to less than one-half of the L- and the E-strand DNA from the \"late\" region. Nuclei of normally growing cells contained the same species found in the cytoplasm, as well as an additional abundant RNA complementary to one-half of the L-strand DNA of the late region. No significant changes occurred in the cytoplasmic viral RNA after mitomycin C treatment before the onset of viral DNA replication, but the concentration of the nuclear L-strand DNA transcript diminished. After the onset of viral DNA replication after mitomycin C treatment, transcripts of virtually the entire L-strand DNA were found in the nuclei, and a 10-fold increase was observed in the abundance of RNA transcribed from the E strand of the early region. In the cytoplasm, the abundance of the early RNA increased about 25-fold and late RNA complementary to the L-strand DNA of the late region was found in a similar quantity. The synthesis of both the early and the late RNA species was inhibited if viral DNA replication was blocked with 5-fluorodeoxyuridine. We conclude that the induction of viral DNA replication in LPT cells is not determined at the level of mRNA synthesis.", "contents": "Polyoma virus-specific RNA synthesis in an inducible line of polyoma virus-transformed rat cells. Viral RNA present in the inducible LPT clone 1A of polyoma virus-transformed rat cells was characterized before and after mitomycin C induction by hybridization with 32P-labeled separated E and L strands of polyoma viral DNA restriction endonuclease fragments. In clone 1A cells maintained under normal growth conditions, the cytoplasm contained a transcript of the E-strand DNA from the \"early\" region similar to that previously identified in lytically infected cells, as well as minor quantities of RNA complementary to less than one-half of the L- and the E-strand DNA from the \"late\" region. Nuclei of normally growing cells contained the same species found in the cytoplasm, as well as an additional abundant RNA complementary to one-half of the L-strand DNA of the late region. No significant changes occurred in the cytoplasmic viral RNA after mitomycin C treatment before the onset of viral DNA replication, but the concentration of the nuclear L-strand DNA transcript diminished. After the onset of viral DNA replication after mitomycin C treatment, transcripts of virtually the entire L-strand DNA were found in the nuclei, and a 10-fold increase was observed in the abundance of RNA transcribed from the E strand of the early region. In the cytoplasm, the abundance of the early RNA increased about 25-fold and late RNA complementary to the L-strand DNA of the late region was found in a similar quantity. The synthesis of both the early and the late RNA species was inhibited if viral DNA replication was blocked with 5-fluorodeoxyuridine. We conclude that the induction of viral DNA replication in LPT cells is not determined at the level of mRNA synthesis."}
{"id": "PMID:205670", "title": "Analysis of cytoplasmic RNA and polyribosmomes from feline leukemia virus-infected cells.", "content": "Cytoplasmic virus-specific RNA and polyribosomes from a chronically infected feline thymus tumor cell line, F-422, were analyzed by using in vitro-synthesized feline leukemia virus (Rickard strain) (R-FeLV) complementary DNA (cDNA) probe. By hybridization kinetics analysis, cytoplasmic, polyribosomat, and nuclear RNAs were found to be 2.1, 2.6, and 0.7% virus specific, respectively. Size classes within subcellular fractions were determined by sucrose gradient centrifugation in the presence of dimethyl sulfoxide followed by hybridization. The cytoplasmic fraction contained a 28S size class, which corresponds to the size of virion subunit RNA, and 36S, 23S, and 15 to 18S RNA species. The virus-specific 36S, 23S, and 15 to 18S species but not the 28S RNA were present in both the total and polyadenylic acid-containing polyribosomal RNA. Anti-FeLV gamma globulin bound to rapidly sedimenting polyribosomes, with the peak binding at 400S. The specificity of the binding for nascent virus-specific protein was determined in control experiments that involved mixing polyribosomes with soluble virion proteins, absorption of specific gamma globulin with soluble virion proteins, and puromycin-induced nascent protein release. The R-FeLV cDNA probe hybridized to RNA in two polyribosomal regions (approximately 400 to 450S and 250S) within the polyribosomal gradients before but not after EDTA treatment. The 400 to 450S polyribosomes contained three major peaks of virus-specific RNA at 36S, 23S, and 15 to 18S, whereas the 250S polyribosomes contained predominantly 36S and 15 to 18S RNA. Further experiments suggest that an approximately 36S minor subunit is present in virion RNA.", "contents": "Analysis of cytoplasmic RNA and polyribosmomes from feline leukemia virus-infected cells. Cytoplasmic virus-specific RNA and polyribosomes from a chronically infected feline thymus tumor cell line, F-422, were analyzed by using in vitro-synthesized feline leukemia virus (Rickard strain) (R-FeLV) complementary DNA (cDNA) probe. By hybridization kinetics analysis, cytoplasmic, polyribosomat, and nuclear RNAs were found to be 2.1, 2.6, and 0.7% virus specific, respectively. Size classes within subcellular fractions were determined by sucrose gradient centrifugation in the presence of dimethyl sulfoxide followed by hybridization. The cytoplasmic fraction contained a 28S size class, which corresponds to the size of virion subunit RNA, and 36S, 23S, and 15 to 18S RNA species. The virus-specific 36S, 23S, and 15 to 18S species but not the 28S RNA were present in both the total and polyadenylic acid-containing polyribosomal RNA. Anti-FeLV gamma globulin bound to rapidly sedimenting polyribosomes, with the peak binding at 400S. The specificity of the binding for nascent virus-specific protein was determined in control experiments that involved mixing polyribosomes with soluble virion proteins, absorption of specific gamma globulin with soluble virion proteins, and puromycin-induced nascent protein release. The R-FeLV cDNA probe hybridized to RNA in two polyribosomal regions (approximately 400 to 450S and 250S) within the polyribosomal gradients before but not after EDTA treatment. The 400 to 450S polyribosomes contained three major peaks of virus-specific RNA at 36S, 23S, and 15 to 18S, whereas the 250S polyribosomes contained predominantly 36S and 15 to 18S RNA. Further experiments suggest that an approximately 36S minor subunit is present in virion RNA."}
{"id": "PMID:205671", "title": "Inhibition of RNA synthesis in mouse myeloma cells infected with vesicular stomatitis virus.", "content": "Infection of mouse myeloma cells (MPC-11) with vesicular stomatitis (VS) virus resulted in rapid and marked reduction in cellular RNA synthesis considerably before cell viability was compromised. Mouse myeloma cells responded maximally to viral infection at a multiplicity of 1 and were considerably more se;sitive to shut-off of RNA synthesis than were mouse L cells or BHK-21 cells. This inhibition of cellular RNA synthesis was shown not to be caused by differential membrane permeability of infected and uninfected MPC-11 cells to [3H]uridine, nor was it due to greater degradation of previously synthesized RNA. VS viral infection appeared not to impede transport of newly synthesized nuclear RNA to the cytoplasm; moreover, infected cells accumulated polyadenylated mRNA at the same rate as did uninfected cells. Polyacrylamide gel electrophoresis of newly synthesized nuclear RNA demonstrated that the polydisperse nature and size distribution were not affected by VS viral infection. Isolated nuclei of infected MPC-11 cells also inhibited greatly impaired capacity to synthesize RNA despite the absence of cytoplasmic factors. Infected-cell cytosol did not inhibit transcription by uninfected-cell nuclei, nor did uninfected-cell cytosol reverse viral inhibition of nuclear transcription. Studies with alpha-amanitin revealed that VS viral infection inhibited the activity of polymerases I, II, and III, but only polymerase II was affected progressively throughout infection and to a much greater extent. These data suggest that, even at low multiplicities of infection, VS virus rapidly shuts off cellular RNA synthesis at the level of nuclear transcription.", "contents": "Inhibition of RNA synthesis in mouse myeloma cells infected with vesicular stomatitis virus. Infection of mouse myeloma cells (MPC-11) with vesicular stomatitis (VS) virus resulted in rapid and marked reduction in cellular RNA synthesis considerably before cell viability was compromised. Mouse myeloma cells responded maximally to viral infection at a multiplicity of 1 and were considerably more se;sitive to shut-off of RNA synthesis than were mouse L cells or BHK-21 cells. This inhibition of cellular RNA synthesis was shown not to be caused by differential membrane permeability of infected and uninfected MPC-11 cells to [3H]uridine, nor was it due to greater degradation of previously synthesized RNA. VS viral infection appeared not to impede transport of newly synthesized nuclear RNA to the cytoplasm; moreover, infected cells accumulated polyadenylated mRNA at the same rate as did uninfected cells. Polyacrylamide gel electrophoresis of newly synthesized nuclear RNA demonstrated that the polydisperse nature and size distribution were not affected by VS viral infection. Isolated nuclei of infected MPC-11 cells also inhibited greatly impaired capacity to synthesize RNA despite the absence of cytoplasmic factors. Infected-cell cytosol did not inhibit transcription by uninfected-cell nuclei, nor did uninfected-cell cytosol reverse viral inhibition of nuclear transcription. Studies with alpha-amanitin revealed that VS viral infection inhibited the activity of polymerases I, II, and III, but only polymerase II was affected progressively throughout infection and to a much greater extent. These data suggest that, even at low multiplicities of infection, VS virus rapidly shuts off cellular RNA synthesis at the level of nuclear transcription."}
{"id": "PMID:205672", "title": "Characterization of the 5'-terminal capped structures of late simian virus 40-specific mRNA.", "content": "32P-labeled, late simian virus 40-specific RNA was isoalted from infected CV1 cells and completely degraded with RNase T2 and bacterial alkaline phosphatase. The RNase-resistant material was fractionated two dimensionally and further characterized with Penicillium nuclease and nucleotide pyrophosphatase. Two major 5' termini were identified in late simian virus 40 RNA, namely, 7-methyl Gppp 2',6-dimethyl ApUp and 7-methyl Gppp 2',6-dimethyl Ap 2'-methyl, UpUp. Both 5' termini are present in unfractionated viral RNA as well as in the separated 16S and 19S species. As both caps differ only in secondary modification, it is possible that they are derived from the same site on the DNA. The relatively higher cap II content of the 16S mRNA may be related to its slower rate of turnover.", "contents": "Characterization of the 5'-terminal capped structures of late simian virus 40-specific mRNA. 32P-labeled, late simian virus 40-specific RNA was isoalted from infected CV1 cells and completely degraded with RNase T2 and bacterial alkaline phosphatase. The RNase-resistant material was fractionated two dimensionally and further characterized with Penicillium nuclease and nucleotide pyrophosphatase. Two major 5' termini were identified in late simian virus 40 RNA, namely, 7-methyl Gppp 2',6-dimethyl ApUp and 7-methyl Gppp 2',6-dimethyl Ap 2'-methyl, UpUp. Both 5' termini are present in unfractionated viral RNA as well as in the separated 16S and 19S species. As both caps differ only in secondary modification, it is possible that they are derived from the same site on the DNA. The relatively higher cap II content of the 16S mRNA may be related to its slower rate of turnover."}
{"id": "PMID:205673", "title": "Intracellular precursors to the major glycoprotein of avian oncoviruses in chicken embryo fibroblasts.", "content": "A 96,000-dalton glycoprotein, p(96), was present in cell extracts obtained from gs-chf- chicken embryo fibroblasts infected with the avian RNA tumor viruses Rous-associated virus-2 subgroup B (RAV-2) and the Schmidt-Ruppin strain of Rous sarcoma virus subgroup A (SR-RSV-A), as well as from uninfected gsLchf+ (HE) cell extracts. It was not found in cell extracts from uninfected gs-chf- or gs+chf+ (HH) cells, nor from gs-chf- cells infected with envelope-deficient Bryan high-titer Rous sarcoma virus. Immunoprecipitation, kinetic, and biochemical data indicate the this polyprotein contains information that gives rise to the major virion glycoprotein gp85. A second polyprotein of 80,000 daltons, p/80), is also present in the RAV-2- and SR-RSV-A-infected gs-chf- cells. This second polyprotein contains less carbohydrate than p(96), and kinetic and biochemical data indicate that p(80) may be an immature form of p(96).", "contents": "Intracellular precursors to the major glycoprotein of avian oncoviruses in chicken embryo fibroblasts. A 96,000-dalton glycoprotein, p(96), was present in cell extracts obtained from gs-chf- chicken embryo fibroblasts infected with the avian RNA tumor viruses Rous-associated virus-2 subgroup B (RAV-2) and the Schmidt-Ruppin strain of Rous sarcoma virus subgroup A (SR-RSV-A), as well as from uninfected gsLchf+ (HE) cell extracts. It was not found in cell extracts from uninfected gs-chf- or gs+chf+ (HH) cells, nor from gs-chf- cells infected with envelope-deficient Bryan high-titer Rous sarcoma virus. Immunoprecipitation, kinetic, and biochemical data indicate the this polyprotein contains information that gives rise to the major virion glycoprotein gp85. A second polyprotein of 80,000 daltons, p/80), is also present in the RAV-2- and SR-RSV-A-infected gs-chf- cells. This second polyprotein contains less carbohydrate than p(96), and kinetic and biochemical data indicate that p(80) may be an immature form of p(96)."}
{"id": "PMID:205674", "title": "Solubilization and characterization of Herpesvirus saimiri-induced membrane antigens.", "content": "Treatment of Herpesvirus saimiri (HVS)-infected owl monkey cells by limited papain digestion removed the HVS-induced membrane antigen (MA) as determined by membrane immunofluorescence and antibody-dependent lymphocyte cytotoxicity (ADLC). Soluble antigenically active HVSMA was detected by inhibition of ADLC and by the decreased binding of 125I-labeled staphylococcus protein A to HVS-infected cells after absorption of an anti-MA-positive serum with papain extracts. Approximately 38% of the inhibitory activity of the papain extracts was sedimentable at 100,000 X g, indicating that the released MA was heterogeneous in size. Preliminary investigations by gel filtration chromatography identified a major peak of MA with a molecular weight between 20,000 and 50,000.", "contents": "Solubilization and characterization of Herpesvirus saimiri-induced membrane antigens. Treatment of Herpesvirus saimiri (HVS)-infected owl monkey cells by limited papain digestion removed the HVS-induced membrane antigen (MA) as determined by membrane immunofluorescence and antibody-dependent lymphocyte cytotoxicity (ADLC). Soluble antigenically active HVSMA was detected by inhibition of ADLC and by the decreased binding of 125I-labeled staphylococcus protein A to HVS-infected cells after absorption of an anti-MA-positive serum with papain extracts. Approximately 38% of the inhibitory activity of the papain extracts was sedimentable at 100,000 X g, indicating that the released MA was heterogeneous in size. Preliminary investigations by gel filtration chromatography identified a major peak of MA with a molecular weight between 20,000 and 50,000."}
{"id": "PMID:205675", "title": "Transformation of BALB/c-3T3 cells by tsA mutants of simian virus 40: temperature sensitivity of the transformed phenotype and retransofrmation by wild-type virus.", "content": "The function of the A gene of simian virus 40 (SV40) in transformation of BALB/c-3T3 cells was investigated by infecting at the permissive temperature with wild-type SV40 and with six tsA mutants whose mutation sites map at different positions in the early region of the SV40 genome. Cloned transformants were then characterized as to the temperature sensitivity of the transformed phenotype. Of 16 tsA transformants, 15 were temperature sensitive for the ability to overgrow a monolayer of normal cells, whereas three of three wild-type transformants were not. This pattern of temperature sensitivity of the transformed phenotype was also observed when selected clones were assessed for the ability to grow in soft agar and in medium containing low concentration of serum. The temperature resistance of the one exceptional tsA transformant could be attributed neither to the location of the mutation site in the transforming virus nor to transformation by a revertant virus. This temperature-resistant tsA transformant, however, was demonstrated to contain a higher intracellular concentration of SV40 T antigen than a temperature-sensitive line transformed by the same tsA mutant. A tsA transformant displaying the untransformed phenotype at the nonpermissive temperature was found to be susceptible to retransformation by wild-type virus at this temperature, demonstrating that the temperature sensitivity of the tsA transformants is due to the viral mutation and not to a cellular defect. These results indicate that continuous expression of the product of the SV40 A gene is required to maintain the transformed phenotype in BALB/c-3T3 cells.", "contents": "Transformation of BALB/c-3T3 cells by tsA mutants of simian virus 40: temperature sensitivity of the transformed phenotype and retransofrmation by wild-type virus. The function of the A gene of simian virus 40 (SV40) in transformation of BALB/c-3T3 cells was investigated by infecting at the permissive temperature with wild-type SV40 and with six tsA mutants whose mutation sites map at different positions in the early region of the SV40 genome. Cloned transformants were then characterized as to the temperature sensitivity of the transformed phenotype. Of 16 tsA transformants, 15 were temperature sensitive for the ability to overgrow a monolayer of normal cells, whereas three of three wild-type transformants were not. This pattern of temperature sensitivity of the transformed phenotype was also observed when selected clones were assessed for the ability to grow in soft agar and in medium containing low concentration of serum. The temperature resistance of the one exceptional tsA transformant could be attributed neither to the location of the mutation site in the transforming virus nor to transformation by a revertant virus. This temperature-resistant tsA transformant, however, was demonstrated to contain a higher intracellular concentration of SV40 T antigen than a temperature-sensitive line transformed by the same tsA mutant. A tsA transformant displaying the untransformed phenotype at the nonpermissive temperature was found to be susceptible to retransformation by wild-type virus at this temperature, demonstrating that the temperature sensitivity of the tsA transformants is due to the viral mutation and not to a cellular defect. These results indicate that continuous expression of the product of the SV40 A gene is required to maintain the transformed phenotype in BALB/c-3T3 cells."}
{"id": "PMID:205676", "title": "T antigen of BK papovavirus in infected and transformed cells.", "content": "BK virus T antigen from BKV-transformed rat and hamster cells and from productively infected monkey cells has been examined by immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Forms of the antigen that migrate as proteins of 86,000 and 92,000 daltons have been identified. Both forms can be labeled by 32P.", "contents": "T antigen of BK papovavirus in infected and transformed cells. BK virus T antigen from BKV-transformed rat and hamster cells and from productively infected monkey cells has been examined by immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Forms of the antigen that migrate as proteins of 86,000 and 92,000 daltons have been identified. Both forms can be labeled by 32P."}
{"id": "PMID:205677", "title": "Physical map of the origin of defective DNA in herpes simplex virus type 1 DNA.", "content": "The origin of defective DNA (dDNA) of the Patton strain of herpes simplex virus type 1 (HSV-1) was physically mapped with BamHI in the parental DNA. The dDNA obtained from virus passaged at high multiplicities of infection was resistant to cleavage with HindIII, whereas digestion with EcoRI yielded a cluster of fragments 5.4 to 5.7 megadaltons (Mdal) in size. Cleavage with BamHI gave a cluster of fragments 2.6 to 3.2 Mdal in size, plus two homogeneous, comigrating 1-Mdal fragments. One of the latter fragments contained the single EcoRI site approximately 65 base pairs from one end. Hybridization of in vitro labeled dDNA probe to EcoRI, HindIII, BamHI, and Hpa I digests of nondefective HSV-1 DNA demonstrated that, in addition to the S-region terminal repeat, only one end of the S region was involved in the generation of this class of dDNA. Thus, the dDNA probe did not hybridize to either the S region 3.0-Mdal HindIIIN fragment or a 3.0-Mdal BamHI fragment of the adjacent 8.7-Mdal HindIIIG fragment, but did hybridize to four BamHI fragments of HindIII G (approximately 5.7 Mdal). The cluster of 2.6- to 3.2-Mdal fragments obtained with BamHI digestion of dDNA appears to represent a novel junction between the termination of dDNA adjacent to the 3.0-Mdal BamHI fragment in HindIII G and the 2.0- to 2.3-Mdal BamHI fragment terminal in HSV-1 DNA.", "contents": "Physical map of the origin of defective DNA in herpes simplex virus type 1 DNA. The origin of defective DNA (dDNA) of the Patton strain of herpes simplex virus type 1 (HSV-1) was physically mapped with BamHI in the parental DNA. The dDNA obtained from virus passaged at high multiplicities of infection was resistant to cleavage with HindIII, whereas digestion with EcoRI yielded a cluster of fragments 5.4 to 5.7 megadaltons (Mdal) in size. Cleavage with BamHI gave a cluster of fragments 2.6 to 3.2 Mdal in size, plus two homogeneous, comigrating 1-Mdal fragments. One of the latter fragments contained the single EcoRI site approximately 65 base pairs from one end. Hybridization of in vitro labeled dDNA probe to EcoRI, HindIII, BamHI, and Hpa I digests of nondefective HSV-1 DNA demonstrated that, in addition to the S-region terminal repeat, only one end of the S region was involved in the generation of this class of dDNA. Thus, the dDNA probe did not hybridize to either the S region 3.0-Mdal HindIIIN fragment or a 3.0-Mdal BamHI fragment of the adjacent 8.7-Mdal HindIIIG fragment, but did hybridize to four BamHI fragments of HindIII G (approximately 5.7 Mdal). The cluster of 2.6- to 3.2-Mdal fragments obtained with BamHI digestion of dDNA appears to represent a novel junction between the termination of dDNA adjacent to the 3.0-Mdal BamHI fragment in HindIII G and the 2.0- to 2.3-Mdal BamHI fragment terminal in HSV-1 DNA."}
{"id": "PMID:205678", "title": "High-molecular-weight RNAs of AKR, NZB, and wild mouse viruses and avian reticuloendotheliosis virus all have similar dimer structures.", "content": "Several 50 to 70S tumor viral RNAs have previously been shown by electron microscopy to be dimers, with the two monomer subunits joined near their 5' ends. Five additional naturally occurring type C RNA tumor viruses have now been examined: AKR, and endogenous murine ecotropic virus; NZB, an endogenous murine xenotropic virus; and ecotropic and an amphotropic virus isolated from a wild mouse; and the avian reticuloendotheliosis virus (REV). All five 50 to 70S RNAs have similar 5'-to-5' dimer structures. Therefore, the observations support the hypothesis that the dimer linkage is a structural feature common to all type C mammalian viruses. REV is the first example of an avian virus with a clear 5'-to 5' dimer linkage. All of the mammalian viral RNAs, but not REV, showed symmetrically placed loops in each subunit of the dimer. Possible molecular structures and biological functions of the dimer linkages and loops are discussed.", "contents": "High-molecular-weight RNAs of AKR, NZB, and wild mouse viruses and avian reticuloendotheliosis virus all have similar dimer structures. Several 50 to 70S tumor viral RNAs have previously been shown by electron microscopy to be dimers, with the two monomer subunits joined near their 5' ends. Five additional naturally occurring type C RNA tumor viruses have now been examined: AKR, and endogenous murine ecotropic virus; NZB, an endogenous murine xenotropic virus; and ecotropic and an amphotropic virus isolated from a wild mouse; and the avian reticuloendotheliosis virus (REV). All five 50 to 70S RNAs have similar 5'-to-5' dimer structures. Therefore, the observations support the hypothesis that the dimer linkage is a structural feature common to all type C mammalian viruses. REV is the first example of an avian virus with a clear 5'-to 5' dimer linkage. All of the mammalian viral RNAs, but not REV, showed symmetrically placed loops in each subunit of the dimer. Possible molecular structures and biological functions of the dimer linkages and loops are discussed."}
{"id": "PMID:205679", "title": "Characterization of DNA-protein complexes from simian adenovirus SA7.", "content": "DNA-protein complexes prepared from purified simian adenovirus SA7 virions and from lytically infected monkey kidney cells exhibited similar properties when compared with respect to size by sucrose gradient centrifugation, to configuration by electron microscopy, and to susceptibility to a variety of treatments by electron microscopy and electrophoresis in agarose gels.", "contents": "Characterization of DNA-protein complexes from simian adenovirus SA7. DNA-protein complexes prepared from purified simian adenovirus SA7 virions and from lytically infected monkey kidney cells exhibited similar properties when compared with respect to size by sucrose gradient centrifugation, to configuration by electron microscopy, and to susceptibility to a variety of treatments by electron microscopy and electrophoresis in agarose gels."}
{"id": "PMID:205680", "title": "Retrovirus purification: method that conserves envelope glycoprotein and maximizes infectivity.", "content": "A Sepharose 4B chromatographic method for purification of retroviruses is described which was less time consuming, increased purified virus yields, conserved viral glycoprotein, and increased recovery of biological infectivity in comparison with conventional sucrose gradient ultracentrifugation techniques.", "contents": "Retrovirus purification: method that conserves envelope glycoprotein and maximizes infectivity. A Sepharose 4B chromatographic method for purification of retroviruses is described which was less time consuming, increased purified virus yields, conserved viral glycoprotein, and increased recovery of biological infectivity in comparison with conventional sucrose gradient ultracentrifugation techniques."}
{"id": "PMID:205681", "title": "RNA tumor virus phosphoproteins: primary structural analysis and identification of phosphopeptides.", "content": "Two-dimensional tryptic peptide mapping was used to compare the peptide sequences of the phosphoprotein (pp12) of cloned ecotropic and amphotropic wild mouse leukemia viruses, strains 1504 and 292. The maps of two ecotropic isolates were very similar to one another, as were the maps of two amphotropic isolates. There was also extensive similarity between the maps of this protein from ecotropic and amphotropic viruses, although characteristic peptide differences were readily recognized. These differences were consistent with the general type specificity of oncovirus phosphoproteins. The pp12 of the field isoalte of 292 virus contained five phosphopeptides, and the non-phosphorylated and variously phosphorylated species of this pp12 showed identical peptide maps, indicating differential phosphorylation of a single polypeptide.", "contents": "RNA tumor virus phosphoproteins: primary structural analysis and identification of phosphopeptides. Two-dimensional tryptic peptide mapping was used to compare the peptide sequences of the phosphoprotein (pp12) of cloned ecotropic and amphotropic wild mouse leukemia viruses, strains 1504 and 292. The maps of two ecotropic isolates were very similar to one another, as were the maps of two amphotropic isolates. There was also extensive similarity between the maps of this protein from ecotropic and amphotropic viruses, although characteristic peptide differences were readily recognized. These differences were consistent with the general type specificity of oncovirus phosphoproteins. The pp12 of the field isoalte of 292 virus contained five phosphopeptides, and the non-phosphorylated and variously phosphorylated species of this pp12 showed identical peptide maps, indicating differential phosphorylation of a single polypeptide."}
{"id": "PMID:205682", "title": "Infectious primate type C virus proviral DNA in productively infected cells.", "content": "Cell lines competent to infection by DNA from cultures chronically infected by type C viruses of the simian sarcoma virus and baboon endogenous virus groups were identified. Significant differences were observed in the relative susceptibility of some cell lines to infection by a given proviral DNA. Practical applications of transfection techniques for the separation of viruses from dually infected cultures and to free virus stocks from mycoplasmal contamination are described.", "contents": "Infectious primate type C virus proviral DNA in productively infected cells. Cell lines competent to infection by DNA from cultures chronically infected by type C viruses of the simian sarcoma virus and baboon endogenous virus groups were identified. Significant differences were observed in the relative susceptibility of some cell lines to infection by a given proviral DNA. Practical applications of transfection techniques for the separation of viruses from dually infected cultures and to free virus stocks from mycoplasmal contamination are described."}
{"id": "PMID:205683", "title": "Transcription of BK virus DNA by Escherichia coli RNA polymerase: size and sequence analysis of RNA.", "content": "Transcription of human papovarirus BK superhelical DNA by Escherichia coli RNA polymerase yielded symmetric RNA with an average chain length of 1,3000 nucleotides.  All regions of human papovavirus BK DNA were equally transcribed.  At least four initiation sites were available to the procaryotic enzyme.", "contents": "Transcription of BK virus DNA by Escherichia coli RNA polymerase: size and sequence analysis of RNA. Transcription of human papovarirus BK superhelical DNA by Escherichia coli RNA polymerase yielded symmetric RNA with an average chain length of 1,3000 nucleotides.  All regions of human papovavirus BK DNA were equally transcribed.  At least four initiation sites were available to the procaryotic enzyme."}
{"id": "PMID:205684", "title": "Antiviral action of a rifamycin derivative: formation Rous sarcoma virus particles deficient in 60 to 70S RNA.", "content": "Growth of Rous sarcoma virus-transformed cells in the presence of rifazone-8(2), a rifamycin derivative, results in the formation of noninfectious virus particles lacking 60 to 70S RNA.", "contents": "Antiviral action of a rifamycin derivative: formation Rous sarcoma virus particles deficient in 60 to 70S RNA. Growth of Rous sarcoma virus-transformed cells in the presence of rifazone-8(2), a rifamycin derivative, results in the formation of noninfectious virus particles lacking 60 to 70S RNA."}
{"id": "PMID:205685", "title": "Autonomic neuropathy and the genitourinary system.", "content": "Autonomic and pudendal neuropathies are frequent and neglected diseases affecting the genitourinary system. In the initial stages they frequently are asymptomatic. Autonomic neuropathy is seen in association with peripheral neuropathy in a wide range of metabolic diseases, including diabetes mellitus. Diagnosis can only be made directly by electrophysiologic methods. Treatment is based upon an adequate laboratory study of genitourinary function.", "contents": "Autonomic neuropathy and the genitourinary system. Autonomic and pudendal neuropathies are frequent and neglected diseases affecting the genitourinary system. In the initial stages they frequently are asymptomatic. Autonomic neuropathy is seen in association with peripheral neuropathy in a wide range of metabolic diseases, including diabetes mellitus. Diagnosis can only be made directly by electrophysiologic methods. Treatment is based upon an adequate laboratory study of genitourinary function."}
{"id": "PMID:205686", "title": "Intraductal carcinoma. Long-term follow-up after treatment by biopsy alone.", "content": "A follow-up period averaging 21.6 years was obtained for patients with low-grade papillary intraductal carcinoma initially treated only by biopsy between 1940 and 1950. Subsequent carcinoma was diagnosed in the same breast in seven of the ten patients after an average interval of 9.7 years. Six of the seven subsequent carcinomas were invasive. Two of the patients died of metastatic carcinoma and two were known to be alive with metastases when last contacted. Three patients were without carcinoma following mastectomy. When these results were combined with the few reports available in the literature, it appeared that at least 39% of patients with intraductal carcinoma treated by biopsy alone subsequently had clinically evident carcinoma, invariably in the same breat, with an average latent period of about ten years. This was undoubtedly a result of the multicentric nature of the disease in many patients.", "contents": "Intraductal carcinoma. Long-term follow-up after treatment by biopsy alone. A follow-up period averaging 21.6 years was obtained for patients with low-grade papillary intraductal carcinoma initially treated only by biopsy between 1940 and 1950. Subsequent carcinoma was diagnosed in the same breast in seven of the ten patients after an average interval of 9.7 years. Six of the seven subsequent carcinomas were invasive. Two of the patients died of metastatic carcinoma and two were known to be alive with metastases when last contacted. Three patients were without carcinoma following mastectomy. When these results were combined with the few reports available in the literature, it appeared that at least 39% of patients with intraductal carcinoma treated by biopsy alone subsequently had clinically evident carcinoma, invariably in the same breat, with an average latent period of about ten years. This was undoubtedly a result of the multicentric nature of the disease in many patients."}
{"id": "PMID:205687", "title": "Evaluation of zoster immune plasma. Treatment of cutaneous disseminated zoster in immunocompromised patients.", "content": "Zoster immune plasma (ZIP) was evaluated for treatment of cutaneous disseminated zoster in immunocompromised hosts. Twenty patients were studied: 13 were enrolled in a double-blind protocol, five received ZIP under an open protocol, and two were observed without receiving a transfusion. In the double-blind study, eight patients actually received ZIP; five were given plasma lacking varicella-zoster virus antibodies (control plasma). The clinical course of zoster in the group given ZIP was the same as that of patients given control plasma or no transfusions. Because ZIP did not alter the clinical course of zoster and because zoster patients produced high-antibody titers without ZIP, we concluded that ZIP is not useful for treatment of cutaneous disseminated zoster and should be reserved for prevention or modification of varicella in exposed, susceptible immunocompromised patients.", "contents": "Evaluation of zoster immune plasma. Treatment of cutaneous disseminated zoster in immunocompromised patients. Zoster immune plasma (ZIP) was evaluated for treatment of cutaneous disseminated zoster in immunocompromised hosts. Twenty patients were studied: 13 were enrolled in a double-blind protocol, five received ZIP under an open protocol, and two were observed without receiving a transfusion. In the double-blind study, eight patients actually received ZIP; five were given plasma lacking varicella-zoster virus antibodies (control plasma). The clinical course of zoster in the group given ZIP was the same as that of patients given control plasma or no transfusions. Because ZIP did not alter the clinical course of zoster and because zoster patients produced high-antibody titers without ZIP, we concluded that ZIP is not useful for treatment of cutaneous disseminated zoster and should be reserved for prevention or modification of varicella in exposed, susceptible immunocompromised patients."}
{"id": "PMID:205701", "title": "[Content of testosterone and of different classes of lipoproteins in the blood plasma of men 40-59 years old].", "content": "The blood plasma of males aged from 40 to 59 (227 practically healthy individual and 48 persons suffering from ischemic heart disease) was tested for the content of testosterone, cholesterol, triglycerides, cholesterol of various classes of lipoproteins and the lipoprotein spectrum by electrophoresis in polyacrylamide gel. It was found that a change in the testosterone level in the blood plasma, even within the limits of physiological values, may affect the plasma lipoprotein spectrum: a decrease in the testosterone concentration is attended with an increase in the content of atherogenic (beta- and pre-beta-) pipoproteins and a decrease in the content of alpha-lipoproteins.", "contents": "[Content of testosterone and of different classes of lipoproteins in the blood plasma of men 40-59 years old]. The blood plasma of males aged from 40 to 59 (227 practically healthy individual and 48 persons suffering from ischemic heart disease) was tested for the content of testosterone, cholesterol, triglycerides, cholesterol of various classes of lipoproteins and the lipoprotein spectrum by electrophoresis in polyacrylamide gel. It was found that a change in the testosterone level in the blood plasma, even within the limits of physiological values, may affect the plasma lipoprotein spectrum: a decrease in the testosterone concentration is attended with an increase in the content of atherogenic (beta- and pre-beta-) pipoproteins and a decrease in the content of alpha-lipoproteins."}
{"id": "PMID:205702", "title": "[Change in the reactions of isolated vascular segments to electric stimulation under the influence of inderal].", "content": "It is shown that under the effect of inderal the relaxation of isolated vascular segments in response to electric stimulation is replaced by their contraction. In the event of initial contractile reactions these are noticeably potentiated. The conditions of the experiment do not allow the effect observed to be explained by the block of specific beta-adrenergic receptors by inderal. Taking into account the data on the effect of inderal on the intracellular biochemical processes, the authors presume that one of the intimate mechanisms of changes in the vascular effects due to inderal are alterations in the content of intracellular calcium.", "contents": "[Change in the reactions of isolated vascular segments to electric stimulation under the influence of inderal]. It is shown that under the effect of inderal the relaxation of isolated vascular segments in response to electric stimulation is replaced by their contraction. In the event of initial contractile reactions these are noticeably potentiated. The conditions of the experiment do not allow the effect observed to be explained by the block of specific beta-adrenergic receptors by inderal. Taking into account the data on the effect of inderal on the intracellular biochemical processes, the authors presume that one of the intimate mechanisms of changes in the vascular effects due to inderal are alterations in the content of intracellular calcium."}
{"id": "PMID:205703", "title": "Influence of steroids on urea-cycle enzymes in chronic human liver disease.", "content": "Activities of Krebs-Henseleit enzymes were determined in liver biopsies of normal persons and in patients suffering from alcoholic hepatitis and chronic active hepatitis. Prednisone was administered for five days in falling dosis (1.5 mg-0.5 mg/kg/body weight) to patients with alcoholic hepatitis and to controls. Patients with chronic active hepatitis received 15-20 mg prednisone daily for more than three months. In healthy persons prednisone did not influence the activities of Krebs-Henseleit enzymes. In patients with alcoholic hepatitis most of the urea-cycle enzymes are significantly decreased (p is less than 0.05) when compared to controls. After glucocorticoid administration enzyme activities remained unchanged. Activities of most of the urea-cycle enzymes are significantly (p is less than 0.05) decreased in untreated patients with chronic active hepatitis. In some of these patients, glucocorticoid administration was associated with a remission as proved by clinical, biochemical and histological data. Activities of the rate-limiting enzymes of the urea-cycle (ASAS, CPS) increased significantly in these patients. By contrast, alterations of enzyme activities could not be observed in patients who failed to respond favourably to steroid treatment.", "contents": "Influence of steroids on urea-cycle enzymes in chronic human liver disease. Activities of Krebs-Henseleit enzymes were determined in liver biopsies of normal persons and in patients suffering from alcoholic hepatitis and chronic active hepatitis. Prednisone was administered for five days in falling dosis (1.5 mg-0.5 mg/kg/body weight) to patients with alcoholic hepatitis and to controls. Patients with chronic active hepatitis received 15-20 mg prednisone daily for more than three months. In healthy persons prednisone did not influence the activities of Krebs-Henseleit enzymes. In patients with alcoholic hepatitis most of the urea-cycle enzymes are significantly decreased (p is less than 0.05) when compared to controls. After glucocorticoid administration enzyme activities remained unchanged. Activities of most of the urea-cycle enzymes are significantly (p is less than 0.05) decreased in untreated patients with chronic active hepatitis. In some of these patients, glucocorticoid administration was associated with a remission as proved by clinical, biochemical and histological data. Activities of the rate-limiting enzymes of the urea-cycle (ASAS, CPS) increased significantly in these patients. By contrast, alterations of enzyme activities could not be observed in patients who failed to respond favourably to steroid treatment."}
{"id": "PMID:205704", "title": "Perhexiline induces generalized lipidosis in rats.", "content": "Administration of perhexiline (Pexide) to rats causes generalized occurrence of lamellated and crystalloid cytoplasmic inclusions which resemble those described in patients with perhexiline-induced polyneuropathy. It is concluded that perhexiline being an amphiphilic cationic compound is a potent inducer of generalized lipidosis.", "contents": "Perhexiline induces generalized lipidosis in rats. Administration of perhexiline (Pexide) to rats causes generalized occurrence of lamellated and crystalloid cytoplasmic inclusions which resemble those described in patients with perhexiline-induced polyneuropathy. It is concluded that perhexiline being an amphiphilic cationic compound is a potent inducer of generalized lipidosis."}
{"id": "PMID:205706", "title": "High granulocyte yield with a simple method of filtration leukapheresis.", "content": "A simple continuous filtration leukapheresis has been devised whereby two Leuko-Pak filters can be charged and eluted within 5 h with approximately 121 of blood in a closed system of tubes. Blood flows by means of gravity without the use of pumps. Without premedication with prednisolone the average yield from 10 donors was 3.66 x 10(10) granulocytes per leukapheresis and after premedication with 150 mg prednisolone orally it was 6.44 x 10(10) granulocytes per leukapheresis. The in vitro function of filter granulocytes was not reduced even after premedication with prednisolone. In comparison with leukapheresis by blood cell separators this modified method of filtration leukapheresis offers the following advantages: 1) the granulocyte yield per litre of whole blood processes is higher, 2) technical assistants in a blood-bank can carry out the method on several donors simultaneously, 3) the method is more economical than leukapheresis by blood cell separators.", "contents": "High granulocyte yield with a simple method of filtration leukapheresis. A simple continuous filtration leukapheresis has been devised whereby two Leuko-Pak filters can be charged and eluted within 5 h with approximately 121 of blood in a closed system of tubes. Blood flows by means of gravity without the use of pumps. Without premedication with prednisolone the average yield from 10 donors was 3.66 x 10(10) granulocytes per leukapheresis and after premedication with 150 mg prednisolone orally it was 6.44 x 10(10) granulocytes per leukapheresis. The in vitro function of filter granulocytes was not reduced even after premedication with prednisolone. In comparison with leukapheresis by blood cell separators this modified method of filtration leukapheresis offers the following advantages: 1) the granulocyte yield per litre of whole blood processes is higher, 2) technical assistants in a blood-bank can carry out the method on several donors simultaneously, 3) the method is more economical than leukapheresis by blood cell separators."}
{"id": "PMID:205705", "title": "Prostaglandin-mediated hypercalcemia: a paraneoplastic syndrome.", "content": "Evidence has been presented for prostaglandin-mediated hypercalcemia and bone resorption in malignancies of both, experimental animals and man. Occurence of hypercalcemia in cancer patients is known for a long time, but its pathogenesis has been poorly understood so far. Besides ectopic parathyroid hormone secretion by tumors, an osteoclast-activating factor released from leukocytes and direct bone destruction by tumor cells, prostaglandins of the E series have to be considered as one of the candicates involved in the pathomechanism of hypercalcemia and osteoclastic osteolysis in cancer patients. This new concept on the pathophysiology of cancer-associated hypercalcemia has implications for the diagnosis and management of this common complication of neoplastic disease.", "contents": "Prostaglandin-mediated hypercalcemia: a paraneoplastic syndrome. Evidence has been presented for prostaglandin-mediated hypercalcemia and bone resorption in malignancies of both, experimental animals and man. Occurence of hypercalcemia in cancer patients is known for a long time, but its pathogenesis has been poorly understood so far. Besides ectopic parathyroid hormone secretion by tumors, an osteoclast-activating factor released from leukocytes and direct bone destruction by tumor cells, prostaglandins of the E series have to be considered as one of the candicates involved in the pathomechanism of hypercalcemia and osteoclastic osteolysis in cancer patients. This new concept on the pathophysiology of cancer-associated hypercalcemia has implications for the diagnosis and management of this common complication of neoplastic disease."}
{"id": "PMID:205724", "title": "Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis.", "content": "Perivascular cells in CNS tissue from six multiple sclerosis (MS) patients and a patient with motor neuron disease were examined by light and electron microscopy. Lymph node tissue from one MS patient was also examined. CNS perivascular macrophages in both MA and motor neuron disease were found to closely resemble free macrophages elsewhere in the body except that they often contained unusually large primary lysosomes. Cytoplasmic inclusions consisting of membrane-bound stacks of curved linear profiles, presumed to be a product of myelin degradation, were constantly observed in microglia in MS plaques but were rarely observed in perivascular macrophages in the same area. Unidentified cylindrical bodies were observed within cysternae of rough endoplasmic reticulum in some lymph node cells. Quantitative studies of the perivascular cell population in one MS case revealed, in histologically normal white matter 260 lymphocytes and 178 plasma cells per cubic millimeter of fresh tissue. Typical chronic plaque tissue without obvious inflammatory cell cuffing contained 1772 plasma cells per cubic millimeter of fresh tissue. No plasma cells were observed in the CNS in motor neuron disease. The results of this study suggest that perivascular macrophages in the CNS represent a specialized population of monocyte-derived free macrophages, that these cells differ functionally from microglial cells, and that the digestion of myelin breakdown products in MS requires the participation of both cell types. The results also suggest that in some chronic MS cases there is a large, permanent population of CNS plasma cells that persists, like the elevated cerebrospinal fluid IgG level in this disease, for the life of the patient, that these cells, rather than inflammatory cells in fresh lesions, are the major source of this raised IgG, and that the existence of such a population of cells may indicate the continuing expression of antigens in chronic MS lesions in the absence of fresh lesion formation.", "contents": "Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Perivascular cells in CNS tissue from six multiple sclerosis (MS) patients and a patient with motor neuron disease were examined by light and electron microscopy. Lymph node tissue from one MS patient was also examined. CNS perivascular macrophages in both MA and motor neuron disease were found to closely resemble free macrophages elsewhere in the body except that they often contained unusually large primary lysosomes. Cytoplasmic inclusions consisting of membrane-bound stacks of curved linear profiles, presumed to be a product of myelin degradation, were constantly observed in microglia in MS plaques but were rarely observed in perivascular macrophages in the same area. Unidentified cylindrical bodies were observed within cysternae of rough endoplasmic reticulum in some lymph node cells. Quantitative studies of the perivascular cell population in one MS case revealed, in histologically normal white matter 260 lymphocytes and 178 plasma cells per cubic millimeter of fresh tissue. Typical chronic plaque tissue without obvious inflammatory cell cuffing contained 1772 plasma cells per cubic millimeter of fresh tissue. No plasma cells were observed in the CNS in motor neuron disease. The results of this study suggest that perivascular macrophages in the CNS represent a specialized population of monocyte-derived free macrophages, that these cells differ functionally from microglial cells, and that the digestion of myelin breakdown products in MS requires the participation of both cell types. The results also suggest that in some chronic MS cases there is a large, permanent population of CNS plasma cells that persists, like the elevated cerebrospinal fluid IgG level in this disease, for the life of the patient, that these cells, rather than inflammatory cells in fresh lesions, are the major source of this raised IgG, and that the existence of such a population of cells may indicate the continuing expression of antigens in chronic MS lesions in the absence of fresh lesion formation."}
{"id": "PMID:205725", "title": "Streptozotocin-induced pancreatic insulitis in mice. Morphologic and physiologic studies.", "content": "Pancreatic insulitis and diabetes mellitus were induced in Charles River CD-1 mice with five subdiabetogenic injections of streptozotocin. Plasma glucose and immunoreactive insulin levels were measured and animals were sacrificed at intervals for morphologic studies of pancreatic islets and measurements of extractable pancreatic immunoreactive insulin. Light microscopy revealed striking insulitis, 5 to 6 days after streptozotocin injections, with cell necrosis and eventual islet atrophy due to beta-cell necrosis, and numerous type C viruses within many of the surviving beta-cells. Light microscopic immunoperoxidase stains of islet cell hormones and electron microscopy identified relatively increased numbers of alpha- and delta-cells within the atrophic islets 6 and 12 months after streptozotocin injections. Plasma  glucose, plasma immunoreactive insulin, and extractable pancreatic immunoreactive insulin measurements documented the persistence of profound hyperglycemia, as well as the reduction of plasma and pancreatic immunoreactive insulin levels. Immunofluorescence studies demonstrated the absence of circulating islet cell antibodies during both the acute and chronic stages of the syndrome. The pathogenesis of this model of insulin-deficient diabetes is believed to be a cell-mediated autoimmune reaction directed against pancreatic beta-cells altered by subdiabetogenic injections of streptozotocin. The importance of the increased number of type C viruses within surviving beta-cells remains obscure.", "contents": "Streptozotocin-induced pancreatic insulitis in mice. Morphologic and physiologic studies. Pancreatic insulitis and diabetes mellitus were induced in Charles River CD-1 mice with five subdiabetogenic injections of streptozotocin. Plasma glucose and immunoreactive insulin levels were measured and animals were sacrificed at intervals for morphologic studies of pancreatic islets and measurements of extractable pancreatic immunoreactive insulin. Light microscopy revealed striking insulitis, 5 to 6 days after streptozotocin injections, with cell necrosis and eventual islet atrophy due to beta-cell necrosis, and numerous type C viruses within many of the surviving beta-cells. Light microscopic immunoperoxidase stains of islet cell hormones and electron microscopy identified relatively increased numbers of alpha- and delta-cells within the atrophic islets 6 and 12 months after streptozotocin injections. Plasma  glucose, plasma immunoreactive insulin, and extractable pancreatic immunoreactive insulin measurements documented the persistence of profound hyperglycemia, as well as the reduction of plasma and pancreatic immunoreactive insulin levels. Immunofluorescence studies demonstrated the absence of circulating islet cell antibodies during both the acute and chronic stages of the syndrome. The pathogenesis of this model of insulin-deficient diabetes is believed to be a cell-mediated autoimmune reaction directed against pancreatic beta-cells altered by subdiabetogenic injections of streptozotocin. The importance of the increased number of type C viruses within surviving beta-cells remains obscure."}
{"id": "PMID:205727", "title": "Distribution and development of angiotensin converting enzyme in the fetal and newborn rabbit. An immunofluorescence study.", "content": "The distribution and development of angiotensin converting enzyme (EC 3.4.15.1) were studied in fetal and newborn rabbits, using fixed tissues embedded in paraffin and stained with a fluorescein-conjugated antibody specific for the enzyme. The enzyme was found at the luminal plasma membrane of endothelial cells from the second third of gestation to the neonatal period. In addition, two types of epithelial cells also contained the enzyme, renal tubular and intestinal. The vascular enzyme may play a role in the regulation of its vasoactive peptide substrates, angiotensin and bradykinin, at term.", "contents": "Distribution and development of angiotensin converting enzyme in the fetal and newborn rabbit. An immunofluorescence study. The distribution and development of angiotensin converting enzyme (EC 3.4.15.1) were studied in fetal and newborn rabbits, using fixed tissues embedded in paraffin and stained with a fluorescein-conjugated antibody specific for the enzyme. The enzyme was found at the luminal plasma membrane of endothelial cells from the second third of gestation to the neonatal period. In addition, two types of epithelial cells also contained the enzyme, renal tubular and intestinal. The vascular enzyme may play a role in the regulation of its vasoactive peptide substrates, angiotensin and bradykinin, at term."}
{"id": "PMID:205731", "title": "Colorectal carcinoma in young black patients: a report of eight cases.", "content": "Colorectal carcinoma in the black population of South Africa is very uncommon when compared with incidence among whites. Even in whites the proportion of patients with colorectal carcinoma under 25 years of age is less than 1% (Hardin, 1972). Eight cases of colorectal carcinoma in black patients under 25 years of age are presented. None had any evidence of premalignant lesions of the colon. The prognosis of colorectal carcinoma in young adults is poor in most series and this group of patients was no exception. Reasons for this poor prognosis are mentioned. A more aggressive approach to the early detection and treatment of the lesion in young patients is essential.", "contents": "Colorectal carcinoma in young black patients: a report of eight cases. Colorectal carcinoma in the black population of South Africa is very uncommon when compared with incidence among whites. Even in whites the proportion of patients with colorectal carcinoma under 25 years of age is less than 1% (Hardin, 1972). Eight cases of colorectal carcinoma in black patients under 25 years of age are presented. None had any evidence of premalignant lesions of the colon. The prognosis of colorectal carcinoma in young adults is poor in most series and this group of patients was no exception. Reasons for this poor prognosis are mentioned. A more aggressive approach to the early detection and treatment of the lesion in young patients is essential."}
{"id": "PMID:205736", "title": "Cholesterol and triglycerides in serum lipoproteins of young persons in Rochester, Minnesota.", "content": "Cholesterol and triglyceride levels in whole sera and in the major lipoprotein fractions are presented for 2,421 children and youths in Rochester, Minnesota, ranging in age from 6 to 18 years. This cross-sectional study revealed subtle changes associated with puberty and the occurrence of certain additional sex-specific changes related to age. Hyperlipoproteinemia was detected in 101 youngsters; those cases exemplified types IIa (61 cases), IIb (5 cases), III (5 cases), and IV (30 cases). One case of type V hyperlipoproteinemia was observed in a second and comparable population sample of 1,245 young persons.", "contents": "Cholesterol and triglycerides in serum lipoproteins of young persons in Rochester, Minnesota. Cholesterol and triglyceride levels in whole sera and in the major lipoprotein fractions are presented for 2,421 children and youths in Rochester, Minnesota, ranging in age from 6 to 18 years. This cross-sectional study revealed subtle changes associated with puberty and the occurrence of certain additional sex-specific changes related to age. Hyperlipoproteinemia was detected in 101 youngsters; those cases exemplified types IIa (61 cases), IIb (5 cases), III (5 cases), and IV (30 cases). One case of type V hyperlipoproteinemia was observed in a second and comparable population sample of 1,245 young persons."}
{"id": "PMID:205744", "title": "Computerized axial-tomography in the preoperative evaluation of an angiofibroma.", "content": "Computerized axial tomography (CAT) of the head provides the otolaryngologist with an effective diagnostic tool. This technique is particularly useful when used in the preoperative evaluation of head and neck pathology and may be used to define the extent of disease and to direct the surgical approach. The case of a 16-year-old male with an extensive angiofibroma involving the paranasal sinuses and nasopharynx is presented as an example of CAT in preoperative planning of the surgical procedure. Computerized tomography was used initially to define the tumor margins. Serial CAT scans were also obtained at intervals during the patient's preoperative estrogen therapy. Evidence was obtained which suggests CAT may be used to monitor the effects of preoperative hormone management of angiofibromas and in the definition of the optimal time for surgery. In the case presented the final CAT scan provided a detailed and accurate description of the tumor margins which were confirmed at surgery. Our experience with a case of an extensive nasopharyngeal angiofibroma demonstrates the CAT scan to be a useful objective diagnostic method for preoperative planning.", "contents": "Computerized axial-tomography in the preoperative evaluation of an angiofibroma. Computerized axial tomography (CAT) of the head provides the otolaryngologist with an effective diagnostic tool. This technique is particularly useful when used in the preoperative evaluation of head and neck pathology and may be used to define the extent of disease and to direct the surgical approach. The case of a 16-year-old male with an extensive angiofibroma involving the paranasal sinuses and nasopharynx is presented as an example of CAT in preoperative planning of the surgical procedure. Computerized tomography was used initially to define the tumor margins. Serial CAT scans were also obtained at intervals during the patient's preoperative estrogen therapy. Evidence was obtained which suggests CAT may be used to monitor the effects of preoperative hormone management of angiofibromas and in the definition of the optimal time for surgery. In the case presented the final CAT scan provided a detailed and accurate description of the tumor margins which were confirmed at surgery. Our experience with a case of an extensive nasopharyngeal angiofibroma demonstrates the CAT scan to be a useful objective diagnostic method for preoperative planning."}
{"id": "PMID:205758", "title": "Adrenal hemorrhage in the adult.", "content": "Bilateral adrenal gland hemorrhage was found in 22 of 2,000 (1.1%) consecutive general hospital autopsies. Clinical features of these 22 patients with diffuse or focal bilateral adrenal hemorrhage have been analyzed and compared with previous series. In our experience, patients with this postmortem finding rarely manifest features of adrenocortical insufficiency and appear instead to die as a consequence of concomitant overwhelming illness, such as septicemia, body surface burns or cardiovascular catastrophe. Two-thirds of the current series had impaired renal function at the time of adrenal hemorrhage and three patients had pituitary gland necrosis. Experimental and clinical observations indicate that the \"stressed\" adrenal gland--under substantive endogenous or exogenous ACTH stimulation--is unusually susceptible to hemorrhage. While our own experience indicates that bilateral adrenal hemorrhage can infrequently be implicated as a factor contributing to patients' death, the possibility of adrenocortical insufficiency must be considered in patients at risk for adrenal hemorrhage. Such patients are those who are azotemic and have bacteremia, burns, or recent cardiovascular catastrophe, particularly when the latter is managed with anticoagulant administration. In these patients, unexplained clinical deterioration or the appearance of findings consistent with adrenocortical insufficiency mandate measurement of serum cortisol concentration and institution of stress-level corticosteroid replacement therapy until a diagnosis of acute adrenocortical insufficiency can be established or refuted.", "contents": "Adrenal hemorrhage in the adult. Bilateral adrenal gland hemorrhage was found in 22 of 2,000 (1.1%) consecutive general hospital autopsies. Clinical features of these 22 patients with diffuse or focal bilateral adrenal hemorrhage have been analyzed and compared with previous series. In our experience, patients with this postmortem finding rarely manifest features of adrenocortical insufficiency and appear instead to die as a consequence of concomitant overwhelming illness, such as septicemia, body surface burns or cardiovascular catastrophe. Two-thirds of the current series had impaired renal function at the time of adrenal hemorrhage and three patients had pituitary gland necrosis. Experimental and clinical observations indicate that the \"stressed\" adrenal gland--under substantive endogenous or exogenous ACTH stimulation--is unusually susceptible to hemorrhage. While our own experience indicates that bilateral adrenal hemorrhage can infrequently be implicated as a factor contributing to patients' death, the possibility of adrenocortical insufficiency must be considered in patients at risk for adrenal hemorrhage. Such patients are those who are azotemic and have bacteremia, burns, or recent cardiovascular catastrophe, particularly when the latter is managed with anticoagulant administration. In these patients, unexplained clinical deterioration or the appearance of findings consistent with adrenocortical insufficiency mandate measurement of serum cortisol concentration and institution of stress-level corticosteroid replacement therapy until a diagnosis of acute adrenocortical insufficiency can be established or refuted."}
{"id": "PMID:205759", "title": "The clinical, radiologic, and pathologic characterization of benign hepatic neoplasms. Alleged association with oral contraceptives.", "content": "Poor histopathologic documentation and confusing terminology have caused focal nodular hyperplasia (FNH) and liver cell adenoma (LCA) to be categorized together as \"benign hepatomas.\" FNH and LCA are distinguishable grossly, microscopically, and ultrastructurally. In a majority of instances they may be differentiated by combined angiography and liver scan: FNH is hypervascular and exhibits normal uptake on scan whereas LCA is hypovascular and cold on scan. FNH almost always follows a benign course, rarely undergoing hemorrhagic necrosis and rupture. FNH does not possess malignant potential; the prognosis, even if unexcised, is excellent. Resection is indicated only if FNH is symptomatic. LCA often ruptures and its malignant potential remains uncertain; the prognosis is guarded and resection is indicated. The literature reported association between FNH and oral contraceptives is anecdotal. However, the recent marked increase in the incidence of LCA's, their almost exclusive occurrence in young women, and the consistent hormonal history strongly suggests an association between oral contraceptive use and LCA's, although here too, statistical evidence is lacking. Prognostic and therapeutic considerations mandate that a clear distinction be made between FNH and LCA.", "contents": "The clinical, radiologic, and pathologic characterization of benign hepatic neoplasms. Alleged association with oral contraceptives. Poor histopathologic documentation and confusing terminology have caused focal nodular hyperplasia (FNH) and liver cell adenoma (LCA) to be categorized together as \"benign hepatomas.\" FNH and LCA are distinguishable grossly, microscopically, and ultrastructurally. In a majority of instances they may be differentiated by combined angiography and liver scan: FNH is hypervascular and exhibits normal uptake on scan whereas LCA is hypovascular and cold on scan. FNH almost always follows a benign course, rarely undergoing hemorrhagic necrosis and rupture. FNH does not possess malignant potential; the prognosis, even if unexcised, is excellent. Resection is indicated only if FNH is symptomatic. LCA often ruptures and its malignant potential remains uncertain; the prognosis is guarded and resection is indicated. The literature reported association between FNH and oral contraceptives is anecdotal. However, the recent marked increase in the incidence of LCA's, their almost exclusive occurrence in young women, and the consistent hormonal history strongly suggests an association between oral contraceptive use and LCA's, although here too, statistical evidence is lacking. Prognostic and therapeutic considerations mandate that a clear distinction be made between FNH and LCA."}
{"id": "PMID:205761", "title": "The purification and polypeptide composition of avian infectious bronchitis virus.", "content": "Purification of egg-grown infectious bronchitis virus (IBV) by sucrose density gradient centrifugation alone, or sucrose density gradient centrifugation plus pH 8.0 treatment, concanavalin A precipitation or metrizamide density gradient centrifugation, failed to produce any differences in the virus polypeptide pattern following polyacrylamide gel electrophoresis in the presence of SDS(SDS-PAGE). SDS-PAGE of purified IBV on 7.5% acrylamide gels separated 16 polypeptides which were detectable by staining with Coomassie blue or measurement of radioactivity following electrophoresis of (3H)-leucine labelled IBV. The molecular weights of the polypeptides were within the range 15,000-135,000. The polypeptides of egg and chick kidney (CK) cell-grown IBV were identical in both size and number but quantitative differences were detected. In particular the relative proportion of the major 52,000 molecular weight polypeptide was greatly reduced in IBV grown in CK cells. SDS-PAGE of purified IBV and staining with Schiff's reagent to detect carbohydrate revealed four.bands with molecular weights of 128,000, 86,000, 67,500 and 37,000. The 128,000 band did not correspond to any of the detected polypeptides. Use of 5% acrylamide gels for SDS-PAGE of IBV failed to resolve all the minor polypeptides and only seven bands were detected.", "contents": "The purification and polypeptide composition of avian infectious bronchitis virus. Purification of egg-grown infectious bronchitis virus (IBV) by sucrose density gradient centrifugation alone, or sucrose density gradient centrifugation plus pH 8.0 treatment, concanavalin A precipitation or metrizamide density gradient centrifugation, failed to produce any differences in the virus polypeptide pattern following polyacrylamide gel electrophoresis in the presence of SDS(SDS-PAGE). SDS-PAGE of purified IBV on 7.5% acrylamide gels separated 16 polypeptides which were detectable by staining with Coomassie blue or measurement of radioactivity following electrophoresis of (3H)-leucine labelled IBV. The molecular weights of the polypeptides were within the range 15,000-135,000. The polypeptides of egg and chick kidney (CK) cell-grown IBV were identical in both size and number but quantitative differences were detected. In particular the relative proportion of the major 52,000 molecular weight polypeptide was greatly reduced in IBV grown in CK cells. SDS-PAGE of purified IBV and staining with Schiff's reagent to detect carbohydrate revealed four.bands with molecular weights of 128,000, 86,000, 67,500 and 37,000. The 128,000 band did not correspond to any of the detected polypeptides. Use of 5% acrylamide gels for SDS-PAGE of IBV failed to resolve all the minor polypeptides and only seven bands were detected."}
{"id": "PMID:205762", "title": "Persistent infection with mouse hepatitis virus of low virulence in nude mice.", "content": "A persisting type of infection with wasting syndrome was established in congenitally athymic nude mice after intraperitoneal inoculation with a mouse hepatitis virus which was not fully pathogenic for heterozygous haired littermates. From the liver, spleen, lymph nodes, and brain of most infected nude mice, the virus was detected at high titers during aperiod from 6 to 35 days postinfection, occurrence of degenerative and necrotic lesions being correlated with virus titers in these organs. The titer of serum neutralizing antibody remained undetectable or very low in most diseases nude mice, whereas some animals resisting the infection could produce antibody at a later stage. In heterozygous haired mice, some lesions were detectable at a very early stage of infection in the spleen and liver, but they seemed to disappear with a marked elevation of the neutralizing antibody titer. Nude mice were able to resist the virus infection when they had previously received transfer of thymocytes from weanling heterozygous littermates.", "contents": "Persistent infection with mouse hepatitis virus of low virulence in nude mice. A persisting type of infection with wasting syndrome was established in congenitally athymic nude mice after intraperitoneal inoculation with a mouse hepatitis virus which was not fully pathogenic for heterozygous haired littermates. From the liver, spleen, lymph nodes, and brain of most infected nude mice, the virus was detected at high titers during aperiod from 6 to 35 days postinfection, occurrence of degenerative and necrotic lesions being correlated with virus titers in these organs. The titer of serum neutralizing antibody remained undetectable or very low in most diseases nude mice, whereas some animals resisting the infection could produce antibody at a later stage. In heterozygous haired mice, some lesions were detectable at a very early stage of infection in the spleen and liver, but they seemed to disappear with a marked elevation of the neutralizing antibody titer. Nude mice were able to resist the virus infection when they had previously received transfer of thymocytes from weanling heterozygous littermates."}
{"id": "PMID:205763", "title": "Comparative studies on cytopathic effects induced by vesicular stomatitis virus in two cell types.", "content": "Infection of mouse L cells with vesicular stomatitis virus (VSV) leads to an extensive cell fusion, while porcine kidney stable (PS) cells infected with VSV show only cell rounding. Therefore, comparative morphological studies on the infection of the two cell lines were carried out using a transmission or scanning electron microscope and an immunofluorescence microscope. PS cells infected with VSV contrasted to L cells infected with the same virus in the following two points; (1) the principal site of VSV maturation was the intracytoplasmic vacuolar membrane in PS cells and the plasma membrane in L cells. However, it was found that viral glycoprotein was present on the cell surface of infected PS cells; (2) the morphological changes at the cell surface of infected PS cells occurred much earlier and were severer than those at the cell surface of infected L cells. From these observations, we discuss the possibility that the surfaceembrane of PS cells is too sensitive to the VSV-induced cell damage to cause cell fusion.", "contents": "Comparative studies on cytopathic effects induced by vesicular stomatitis virus in two cell types. Infection of mouse L cells with vesicular stomatitis virus (VSV) leads to an extensive cell fusion, while porcine kidney stable (PS) cells infected with VSV show only cell rounding. Therefore, comparative morphological studies on the infection of the two cell lines were carried out using a transmission or scanning electron microscope and an immunofluorescence microscope. PS cells infected with VSV contrasted to L cells infected with the same virus in the following two points; (1) the principal site of VSV maturation was the intracytoplasmic vacuolar membrane in PS cells and the plasma membrane in L cells. However, it was found that viral glycoprotein was present on the cell surface of infected PS cells; (2) the morphological changes at the cell surface of infected PS cells occurred much earlier and were severer than those at the cell surface of infected L cells. From these observations, we discuss the possibility that the surfaceembrane of PS cells is too sensitive to the VSV-induced cell damage to cause cell fusion."}
{"id": "PMID:205766", "title": "The prevalence of antibody to hepatitis A virus in two populations in Victoria.", "content": "Sera collected from a group of 1053 Victorians were tested for antibody to hepatitis A virus by solid phase radioimmunoassay. The group comprised approximately equal numbers of males and females of all ages, 488 of whom lived in Melbourne and 565 in six provincial cities. In both the metropolitan and provincial groups, the prevalence of antibody to hepatitis. A virus was independent of sex and increased steadily with age. Antibody was detected in approximately 20% of children by the age of 10 years, in 40% at 40 years and in excess of 95% above the age of 60 years.", "contents": "The prevalence of antibody to hepatitis A virus in two populations in Victoria. Sera collected from a group of 1053 Victorians were tested for antibody to hepatitis A virus by solid phase radioimmunoassay. The group comprised approximately equal numbers of males and females of all ages, 488 of whom lived in Melbourne and 565 in six provincial cities. In both the metropolitan and provincial groups, the prevalence of antibody to hepatitis. A virus was independent of sex and increased steadily with age. Antibody was detected in approximately 20% of children by the age of 10 years, in 40% at 40 years and in excess of 95% above the age of 60 years."}
{"id": "PMID:205775", "title": "Studies on the kinetic effects of cyclic nucleotides dependent glutamate dehydrogenase.", "content": "Stopped-flow spectrophotometric studies of the reductive amination of L-ketoglutarate by L-glutamate dehydrogenase showed a biphase time course, which consisted of a rapid first phase lasting 60-100 msec and a slow final phase in which the rate of coenzyme oxidation increased until the coenzyme was depleted. The effects of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) on the time course of both phases were established. The results showed that in the concentration ranges used the cyclic nucleotides accelerate the catalytic reaction. The effect of cAMP was more pronounced as compared to cGMP. In all cases this influence was most clearly expressed in the first phase. Using an Arrhenius plot the activation parameters were calculated. The experiments with cAMP and cGMP at different molar ratios showed that a specific cAMP binding may occur.", "contents": "Studies on the kinetic effects of cyclic nucleotides dependent glutamate dehydrogenase. Stopped-flow spectrophotometric studies of the reductive amination of L-ketoglutarate by L-glutamate dehydrogenase showed a biphase time course, which consisted of a rapid first phase lasting 60-100 msec and a slow final phase in which the rate of coenzyme oxidation increased until the coenzyme was depleted. The effects of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) on the time course of both phases were established. The results showed that in the concentration ranges used the cyclic nucleotides accelerate the catalytic reaction. The effect of cAMP was more pronounced as compared to cGMP. In all cases this influence was most clearly expressed in the first phase. Using an Arrhenius plot the activation parameters were calculated. The experiments with cAMP and cGMP at different molar ratios showed that a specific cAMP binding may occur."}
{"id": "PMID:205776", "title": "Localization of host poly(A)+ mRNA in the ribosome profile of mengovirus-infected Ehrlich ascites tumor cells.", "content": "The distribution of poly(A)+ mRNA among polysomes, monosomes, and ribosome-free supernatant fractions after mengovirus infection of Ehrlich ascites tumor (EAT) cells was investigated employing sucrose gradient centrifugation of their corresponding postnuclear supernatants. Poly(A)+ mRNA was isolated from sucrose gradient fractions and quantitated in a cell-free protein synthesizing system from uninfected EAT cells. It was also localized by annealing [3H]-poly(U) to the poly(A)-tracts of mRNA present in the sucrose gradient fractions. Both experiments revealed a gradual shift of host poly(A)+ mRNA from large to small polysomes and monosomes, respectively, with the time postinfection. The greatest part of host template RNA appears to remain ribosome-bound and only a fraction seems to be detached from the ribosomes in the course of mengovirus infection. At the end of the infectious cycle, 8 h postinfection, approximately 70% of the poly(A)+ mRNA detected in uninfected cells is still biologically active, but not translated in vivo, in agreement with data from the [3H]poly(U)hybridization experiment.", "contents": "Localization of host poly(A)+ mRNA in the ribosome profile of mengovirus-infected Ehrlich ascites tumor cells. The distribution of poly(A)+ mRNA among polysomes, monosomes, and ribosome-free supernatant fractions after mengovirus infection of Ehrlich ascites tumor (EAT) cells was investigated employing sucrose gradient centrifugation of their corresponding postnuclear supernatants. Poly(A)+ mRNA was isolated from sucrose gradient fractions and quantitated in a cell-free protein synthesizing system from uninfected EAT cells. It was also localized by annealing [3H]-poly(U) to the poly(A)-tracts of mRNA present in the sucrose gradient fractions. Both experiments revealed a gradual shift of host poly(A)+ mRNA from large to small polysomes and monosomes, respectively, with the time postinfection. The greatest part of host template RNA appears to remain ribosome-bound and only a fraction seems to be detached from the ribosomes in the course of mengovirus infection. At the end of the infectious cycle, 8 h postinfection, approximately 70% of the poly(A)+ mRNA detected in uninfected cells is still biologically active, but not translated in vivo, in agreement with data from the [3H]poly(U)hybridization experiment."}
{"id": "PMID:205779", "title": "[Clinical aspects, diagnosis and treatment of organic hyperinsulinism. Experience with 46 operated patients (author's transl)].", "content": "The clinical picture of organic hyperinsulinism is presented with reference to experience in 46 operated patients. For the recognition of disease, a careful history is a decisive contribution. The hunger test showed a characteristic hypoglycemic reaction in 100%; the tolbutamide test gave a positive result in 92%. Insulinomas could be localized angiographically in 71%; in one patient this could only be done with an ERCT. The treatment of choice is operation as soon as possible. If possible, enucleation is to be given preference over pancreas resection because of the low complication rate. A search for ectopic (2%) and multiple (12%) adenomas is important. A cure was achieved in 76% of all those operated on. The hospital mortality was about 4%.", "contents": "[Clinical aspects, diagnosis and treatment of organic hyperinsulinism. Experience with 46 operated patients (author's transl)]. The clinical picture of organic hyperinsulinism is presented with reference to experience in 46 operated patients. For the recognition of disease, a careful history is a decisive contribution. The hunger test showed a characteristic hypoglycemic reaction in 100%; the tolbutamide test gave a positive result in 92%. Insulinomas could be localized angiographically in 71%; in one patient this could only be done with an ERCT. The treatment of choice is operation as soon as possible. If possible, enucleation is to be given preference over pancreas resection because of the low complication rate. A search for ectopic (2%) and multiple (12%) adenomas is important. A cure was achieved in 76% of all those operated on. The hospital mortality was about 4%."}
{"id": "PMID:205781", "title": "Methyl methanesulphonate mutagenesis in L5178Y mouse lymphoma cells.", "content": "The alkylating agent MMS was toxic to mouse lymphoma L5178Y cells and decreased their growth rate. A dose-dependent induction of thioguanine- and thymidine- but not ouabain-resistant variants was observed. The prolonged period for expression of thioguanine-resistant variants observed with other mutagens was also found in these studies. A comparison of MMS and EMS showed that MMS on a molar basis was approximately 10 times more toxic than EMS. With mutation, however, when evaluated at equal levels of cell killing MMS and EMS induced the same number of thymidine-resistant variants. For thioguanine-resistant variants MMS was approximately 10-fold less efficient than EMS, while for ouabain-resistance MMS, unlike EMBS, produced no variants at all. The ouabain results were further compared with positive results obtained using a modified Luria--Delbr\u00fcck fluctuation test.", "contents": "Methyl methanesulphonate mutagenesis in L5178Y mouse lymphoma cells. The alkylating agent MMS was toxic to mouse lymphoma L5178Y cells and decreased their growth rate. A dose-dependent induction of thioguanine- and thymidine- but not ouabain-resistant variants was observed. The prolonged period for expression of thioguanine-resistant variants observed with other mutagens was also found in these studies. A comparison of MMS and EMS showed that MMS on a molar basis was approximately 10 times more toxic than EMS. With mutation, however, when evaluated at equal levels of cell killing MMS and EMS induced the same number of thymidine-resistant variants. For thioguanine-resistant variants MMS was approximately 10-fold less efficient than EMS, while for ouabain-resistance MMS, unlike EMBS, produced no variants at all. The ouabain results were further compared with positive results obtained using a modified Luria--Delbr\u00fcck fluctuation test."}
{"id": "PMID:205782", "title": "Post-treatment with caffeine and the induction of gene mutations by ultraviolet irradiation and ethyl methanesulphonate in V-79 Chinese hamster cells in culture.", "content": "The effect of caffeine on V-79 Chinese hamster cells after ultraviolet irradiation or treated with ethyl methanesulphonate was investigated. Caffeine strongly potentiated the killing of both agents, but it had no effect on the induction of mutations at the hypoxanthine-guanine phosphoribosyl transferase locus. The results are consistent with the notion that caffeine slows down an error-prone post-replicative repair mechanism without changing the mutation frequency.", "contents": "Post-treatment with caffeine and the induction of gene mutations by ultraviolet irradiation and ethyl methanesulphonate in V-79 Chinese hamster cells in culture. The effect of caffeine on V-79 Chinese hamster cells after ultraviolet irradiation or treated with ethyl methanesulphonate was investigated. Caffeine strongly potentiated the killing of both agents, but it had no effect on the induction of mutations at the hypoxanthine-guanine phosphoribosyl transferase locus. The results are consistent with the notion that caffeine slows down an error-prone post-replicative repair mechanism without changing the mutation frequency."}
{"id": "PMID:205783", "title": "Expression of a bacterial gene turned on by a potent carcinogen.", "content": "Contrary to mutagenesis, lysogenic induction produced by chemical carcinogens occurs in the majority of a population of lysogenic cells. Such a mass effect can therefore be measured at the biochemical level using an E. coli tester strain in which the galactose operon has been put under the negative control of the lambda repressor. In this publication we show that galactokinase synthesis is turned on by aflatoxin B1 metabolites within an hour after treatment of the tester bacteria. Such a biochemical assay provides a useful means for identifying potential chemical carcinogens.", "contents": "Expression of a bacterial gene turned on by a potent carcinogen. Contrary to mutagenesis, lysogenic induction produced by chemical carcinogens occurs in the majority of a population of lysogenic cells. Such a mass effect can therefore be measured at the biochemical level using an E. coli tester strain in which the galactose operon has been put under the negative control of the lambda repressor. In this publication we show that galactokinase synthesis is turned on by aflatoxin B1 metabolites within an hour after treatment of the tester bacteria. Such a biochemical assay provides a useful means for identifying potential chemical carcinogens."}
{"id": "PMID:205786", "title": "Search for the uremic toxin. Decreased motor-nerve conduction velocity and elevated parathyroid hormone in uremia.", "content": "In a retrospective analysis to determine whether secondary hyperparathyroidism in uremia has a role in uremic peripheral neuropathy, we simultaneously measured motor-nerve conduction velocity and serum parathormone level in 42 uremic patients. We compared age-matched groups of nondiabetic uremic patients, divided into three groups according to serum parathyroid hormone, for degree of impairment of motor-nerve conduction velocity, and 12 diabetic patients with uremia. The group with highest levels had a significantly (P less than 0.01) lower conduction velocity (25.3 +/- 4.9 m per second) than the group with normal or slightly elevated parathyroid hormone, who had only mild depression of nerve conduction (45.1 +/- 1.3 m per second). Mean serum calcium and creatinine were not significantly different between groups. Nerve conduction velocity was similarly depressed in 17 patients on additional dialysis studied prospectively and divided into groups according to parathyroid hormone levels. These results suggest a relation between high parathormone levels and uremic neuropathy and implicate parathyroid hormone as a uremic toxin.", "contents": "Search for the uremic toxin. Decreased motor-nerve conduction velocity and elevated parathyroid hormone in uremia. In a retrospective analysis to determine whether secondary hyperparathyroidism in uremia has a role in uremic peripheral neuropathy, we simultaneously measured motor-nerve conduction velocity and serum parathormone level in 42 uremic patients. We compared age-matched groups of nondiabetic uremic patients, divided into three groups according to serum parathyroid hormone, for degree of impairment of motor-nerve conduction velocity, and 12 diabetic patients with uremia. The group with highest levels had a significantly (P less than 0.01) lower conduction velocity (25.3 +/- 4.9 m per second) than the group with normal or slightly elevated parathyroid hormone, who had only mild depression of nerve conduction (45.1 +/- 1.3 m per second). Mean serum calcium and creatinine were not significantly different between groups. Nerve conduction velocity was similarly depressed in 17 patients on additional dialysis studied prospectively and divided into groups according to parathyroid hormone levels. These results suggest a relation between high parathormone levels and uremic neuropathy and implicate parathyroid hormone as a uremic toxin."}
{"id": "PMID:205788", "title": "Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man.", "content": "We investigated the antihypertensive effect of the angiotensin converting-enzyme inhibitor SQ 14225 in 12 hypertensive patients for periods of three to 24 weeks. Blood pressure decreased in all patients (from 177 +/- 8/110 +/- 2 to 136 +/- 6/88 +/- 2 mm Hg--mean +/- S.E.); oral doses ranged from 400 to 1000 mg daily. Concomitant effects noted were small increases in plasma potassium concentration and pulse rate. One patient experienced a transient febrile reaction. Plasma renin activity rose during treatment, plasma aldosterone decreased, and angiotensin-converting-enzyme activity was virtually eliminated. There was no significant correlation between pretreatment plasma renin activity and degree of blood-pressure fall with SQ 14225. The exact mechanisms contributing to the blood-pressure-lowering effect of this agent remain unclear. SQ 14225 is a promising new antihypertensive agent, effective in patients refractory to traditional medical therapy.", "contents": "Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man. We investigated the antihypertensive effect of the angiotensin converting-enzyme inhibitor SQ 14225 in 12 hypertensive patients for periods of three to 24 weeks. Blood pressure decreased in all patients (from 177 +/- 8/110 +/- 2 to 136 +/- 6/88 +/- 2 mm Hg--mean +/- S.E.); oral doses ranged from 400 to 1000 mg daily. Concomitant effects noted were small increases in plasma potassium concentration and pulse rate. One patient experienced a transient febrile reaction. Plasma renin activity rose during treatment, plasma aldosterone decreased, and angiotensin-converting-enzyme activity was virtually eliminated. There was no significant correlation between pretreatment plasma renin activity and degree of blood-pressure fall with SQ 14225. The exact mechanisms contributing to the blood-pressure-lowering effect of this agent remain unclear. SQ 14225 is a promising new antihypertensive agent, effective in patients refractory to traditional medical therapy."}
{"id": "PMID:205789", "title": "Vitamin-D-dependent rickets type II. Resistance of target organs to 1,25-dihydroxyvitamin D.", "content": "Studies were done to determine the cause for hypocalcemia, secondary hyperparathyroidism, osteomalacia and osteitis fibrosa cystica in a 22-year-old black woman. The patient had normal serum 25-hydroxyvitamin D (14 ng per milliliter) and markedly elevated serum 1,25-dihydroxyvitamin D (137 pg per milliliter). Vitamin D3, 4000 units per day for four weeks, increased the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to as high as 29 and 297 pg per milliliter, respectively, and corrected the hypocalcemia and secondary hyperparathyroidism. The results suggest that the disorder results from impaired end-organ response to 1,25-dihydroxyvitamin D. We propose that the entity be called vitamin-D-dependent rickets Type II.", "contents": "Vitamin-D-dependent rickets type II. Resistance of target organs to 1,25-dihydroxyvitamin D. Studies were done to determine the cause for hypocalcemia, secondary hyperparathyroidism, osteomalacia and osteitis fibrosa cystica in a 22-year-old black woman. The patient had normal serum 25-hydroxyvitamin D (14 ng per milliliter) and markedly elevated serum 1,25-dihydroxyvitamin D (137 pg per milliliter). Vitamin D3, 4000 units per day for four weeks, increased the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to as high as 29 and 297 pg per milliliter, respectively, and corrected the hypocalcemia and secondary hyperparathyroidism. The results suggest that the disorder results from impaired end-organ response to 1,25-dihydroxyvitamin D. We propose that the entity be called vitamin-D-dependent rickets Type II."}
{"id": "PMID:205792", "title": "9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group.", "content": "Of a series of nucleoside analogues synthesised, 9-(2-hydroxyethoxymethyl) guanine was found to have marked antiviral activity in animal models of herpes virus infections, associated with very low toxicity.", "contents": "9-(2-hydroxyethoxymethyl) guanine activity against viruses of the herpes group. Of a series of nucleoside analogues synthesised, 9-(2-hydroxyethoxymethyl) guanine was found to have marked antiviral activity in animal models of herpes virus infections, associated with very low toxicity."}
{"id": "PMID:205795", "title": "Membrane leakiness after viral infection and a new approach to the development of antiviral agents.", "content": "Viral development induces changes in the permeability properties of the plasma membrane of the host cell. Here it is shown that, because of this leakiness, inhibitors of protein synthesis normally impermeable to uninfected cells are able to enter infected cells and thereby specifically inhibit viral protein synthesis.", "contents": "Membrane leakiness after viral infection and a new approach to the development of antiviral agents. Viral development induces changes in the permeability properties of the plasma membrane of the host cell. Here it is shown that, because of this leakiness, inhibitors of protein synthesis normally impermeable to uninfected cells are able to enter infected cells and thereby specifically inhibit viral protein synthesis."}
{"id": "PMID:205802", "title": "Complete nucleotide sequence of SV40 DNA.", "content": "The determination of the total 5,224 base-pair DNA sequence of the virus SV40 has enabled us to locate precisely the known genes on the genome. At least 15.2% of the genome is presumably not translated into polypeptides. Particular points of interest revealed by the complete sequence are the initiation of the early t and T antigens at the same position and the fact that the T antigen is coded by two non-contiguous regions of the genome; the T antigen mRNA is spliced in the coding region. In the late region the gene for the major protein VP1 overlaps those for proteins VP2 and VP3 over 122 nucleotides but is read in a different frame. The almost complete amino acid sequences of the two early proteins as well as those of the late proteins have been deduced from the nucleotide sequence. The mRNAs for the latter three proteins are presumably spliced out of a common primary RNA transcript. The use of degenerate codons is decidedly non-random, but is similar for the early and late regions. Codons of the type NUC, NCG and CGN are absent or very rare.", "contents": "Complete nucleotide sequence of SV40 DNA. The determination of the total 5,224 base-pair DNA sequence of the virus SV40 has enabled us to locate precisely the known genes on the genome. At least 15.2% of the genome is presumably not translated into polypeptides. Particular points of interest revealed by the complete sequence are the initiation of the early t and T antigens at the same position and the fact that the T antigen is coded by two non-contiguous regions of the genome; the T antigen mRNA is spliced in the coding region. In the late region the gene for the major protein VP1 overlaps those for proteins VP2 and VP3 over 122 nucleotides but is read in a different frame. The almost complete amino acid sequences of the two early proteins as well as those of the late proteins have been deduced from the nucleotide sequence. The mRNAs for the latter three proteins are presumably spliced out of a common primary RNA transcript. The use of degenerate codons is decidedly non-random, but is similar for the early and late regions. Codons of the type NUC, NCG and CGN are absent or very rare."}
{"id": "PMID:205805", "title": "[Etiology and pathogenesis of arteriosclerosis].", "content": "Cardiovascular diseases are the leading cause of death in Western countries, with an enormous increase in death rate and involvement of younger age groups during the last decades. This applies especially to coronary heart disease and is mainly caused by first-degree risk factors: hypertension, hyperlipoproteinemia, cigarette smoking, gout, obesity, polycythemia, lack of physical activity, and stress. These risk factors are discussed with special reference to overnutrition and increased cholesterol levels. Recent resuults of research concerning lipids and their relation to atherosclerosis are reviewed.", "contents": "[Etiology and pathogenesis of arteriosclerosis]. Cardiovascular diseases are the leading cause of death in Western countries, with an enormous increase in death rate and involvement of younger age groups during the last decades. This applies especially to coronary heart disease and is mainly caused by first-degree risk factors: hypertension, hyperlipoproteinemia, cigarette smoking, gout, obesity, polycythemia, lack of physical activity, and stress. These risk factors are discussed with special reference to overnutrition and increased cholesterol levels. Recent resuults of research concerning lipids and their relation to atherosclerosis are reviewed."}
{"id": "PMID:205806", "title": "The movement of plutonium, americium, and curium through the food chain.", "content": "The actinides, plutonium, americium and curium, are being produced in increasing quantites as the nuclear programme is expanded. As these alpha-particle-emitting elements are hazardous to man there is considerable concern about the movement of these elements through the environment; The uptake of these elements from soil into the plants is low, as is the gastrointestinal concentration factor. Although there are complexing agents in the environment which have been shown to complex these elements there is no evidence that these complexing agents might bring about a concentration of actinides in the food chain of man.", "contents": "The movement of plutonium, americium, and curium through the food chain. The actinides, plutonium, americium and curium, are being produced in increasing quantites as the nuclear programme is expanded. As these alpha-particle-emitting elements are hazardous to man there is considerable concern about the movement of these elements through the environment; The uptake of these elements from soil into the plants is low, as is the gastrointestinal concentration factor. Although there are complexing agents in the environment which have been shown to complex these elements there is no evidence that these complexing agents might bring about a concentration of actinides in the food chain of man."}
{"id": "PMID:205808", "title": "Nucleic acids from subcellular fractions of N-nitrosodiethylamine-induced hepatoma in mice. II. Changes in gene expression during tumor progression.", "content": "The hybridization properties of in vivo labeled nuclear and mitochondrial ribonucleic acids of an transplantable hepatoma were studied. It was shown that during tumor progression the repression of nuclear genome revelead at its early stages was replaced by the de-repression at its later stages. The hybridizability of mitochondrial RNA with nuclear DNA was not changed.", "contents": "Nucleic acids from subcellular fractions of N-nitrosodiethylamine-induced hepatoma in mice. II. Changes in gene expression during tumor progression. The hybridization properties of in vivo labeled nuclear and mitochondrial ribonucleic acids of an transplantable hepatoma were studied. It was shown that during tumor progression the repression of nuclear genome revelead at its early stages was replaced by the de-repression at its later stages. The hybridizability of mitochondrial RNA with nuclear DNA was not changed."}
{"id": "PMID:205809", "title": "Experimental hypoglycemizing tumor of B-cells of Langerhans islets produced by the combined action of streptozotocin annd nicotinamide in the rat.", "content": "Young male and female Wistar-Velaz rats were treated with streptozotocin-nicotinamide combination according to the method of Rakieten and examined periodically for 23 months for fasting and postprandial glycemia, by intravenous, intraperitoneal or intragastric glucose tolerance and tolbutamide tests with the aim to detect in vivo the experimentally produced nesidiomas. One male rat with severe hypoglycemia, apparent first on tolbutamide test after twelve months, later also on glucose tolerance test and fasting hypoglycemia associated with paraplegia with macroscopically and microscopically documented nesidioma is described. The exstirpation of this nesidioma was followed first by normalization and later by development of latent diabetes.", "contents": "Experimental hypoglycemizing tumor of B-cells of Langerhans islets produced by the combined action of streptozotocin annd nicotinamide in the rat. Young male and female Wistar-Velaz rats were treated with streptozotocin-nicotinamide combination according to the method of Rakieten and examined periodically for 23 months for fasting and postprandial glycemia, by intravenous, intraperitoneal or intragastric glucose tolerance and tolbutamide tests with the aim to detect in vivo the experimentally produced nesidiomas. One male rat with severe hypoglycemia, apparent first on tolbutamide test after twelve months, later also on glucose tolerance test and fasting hypoglycemia associated with paraplegia with macroscopically and microscopically documented nesidioma is described. The exstirpation of this nesidioma was followed first by normalization and later by development of latent diabetes."}
{"id": "PMID:205810", "title": "Effect of proteinase inhibitor in experimental tumors.", "content": "Aprotinin, a wide range proteinase inhibitor, was given alone to tumor-bearing mice and life span and several tumor growth parameters were recordered. Aprotinin showed anti-tumor effects in Hepatoma 22 and Lewis lung carcinoma, remaining ineffective in Sarcoma 37, Leukemia L1210 and Ehrlich ascitic carcinoma.", "contents": "Effect of proteinase inhibitor in experimental tumors. Aprotinin, a wide range proteinase inhibitor, was given alone to tumor-bearing mice and life span and several tumor growth parameters were recordered. Aprotinin showed anti-tumor effects in Hepatoma 22 and Lewis lung carcinoma, remaining ineffective in Sarcoma 37, Leukemia L1210 and Ehrlich ascitic carcinoma."}
{"id": "PMID:205812", "title": "Percutaneous electro stimulation of the trigeminal nerve in patients with atypical trigeminal neuralgia.", "content": "In eleven patients with atypical trigeminal neuralgia, following herpes infections or radiation therapy of cancer of the epipharynx, percutaneous electrical stimulation of the trigeminal tract or in the vicinity of the nucleus area was performed. Relief of pain lasting from fourteen days up to six weeks could be obtained.", "contents": "Percutaneous electro stimulation of the trigeminal nerve in patients with atypical trigeminal neuralgia. In eleven patients with atypical trigeminal neuralgia, following herpes infections or radiation therapy of cancer of the epipharynx, percutaneous electrical stimulation of the trigeminal tract or in the vicinity of the nucleus area was performed. Relief of pain lasting from fourteen days up to six weeks could be obtained."}
{"id": "PMID:205813", "title": "Sleep patterns in growth hormone deficient children and age-matched controls: developmental considerations.", "content": "Ten patients with isolated growth hormone (GH) deficiency and 13 age-matched normal controls were studied. All patients were below the 3rd percentile in height and weight. All but 1 subject were studied for 3 or 4 consecutive nights in the sleep laboratory which included monitoring of the EEG, EOG, EMG, and EKG. GH samples were taken during sleep in 6 of the 10 patients. There were no significant differences in the slow-wave sleep (SWS) parameter between the 2 groups, nor was there any difference when all growth hormone patients were compared to controls. The age group comparisons for the percent of rapid eye movement (REM) sleep parameter revealed a significant difference between GH and controls for the youngest group only (p less than 0.05). Similar results were obtained when the GH subjects were grouped according to bone age. A significant decline in SWS was found with increasing chronological age (p less than 0.02), while the REM parameter did not show any significant changes across age categories. None of the patients showed a sleep-related peak in GH secretion. These data are not compatible with the hypothesis of a monotonic relationship between SWS and GH secretion.", "contents": "Sleep patterns in growth hormone deficient children and age-matched controls: developmental considerations. Ten patients with isolated growth hormone (GH) deficiency and 13 age-matched normal controls were studied. All patients were below the 3rd percentile in height and weight. All but 1 subject were studied for 3 or 4 consecutive nights in the sleep laboratory which included monitoring of the EEG, EOG, EMG, and EKG. GH samples were taken during sleep in 6 of the 10 patients. There were no significant differences in the slow-wave sleep (SWS) parameter between the 2 groups, nor was there any difference when all growth hormone patients were compared to controls. The age group comparisons for the percent of rapid eye movement (REM) sleep parameter revealed a significant difference between GH and controls for the youngest group only (p less than 0.05). Similar results were obtained when the GH subjects were grouped according to bone age. A significant decline in SWS was found with increasing chronological age (p less than 0.02), while the REM parameter did not show any significant changes across age categories. None of the patients showed a sleep-related peak in GH secretion. These data are not compatible with the hypothesis of a monotonic relationship between SWS and GH secretion."}
{"id": "PMID:205814", "title": "Lymphocyte ultrastructure in two cases of neuronal ceroid-lipofuscinosis.", "content": "Circulating blood lymphocytes from two patients with neuronal ceroid-lipofuscinosis (NCL) were investigated by transmission electronmicroscopy. Ultrastructural examination showed two forms of intracytoplasmic single membrane-limited inclusions. Contents of the first inclusion form were arranged in five distinct patterns: (1) granules, (2) membranous formations, (3) paracrystalline forms, (4) alternating electron-dense/electron-lucent arrangements, and (5) admixtures of these components. These molecular morphologies suggest the usefulness of lymphocyte fine structure as a diagnostic tool in NCL. The second inclusion form contained cylinder-like structures. These structures are not specific for NCL and have been identified in other diseases.", "contents": "Lymphocyte ultrastructure in two cases of neuronal ceroid-lipofuscinosis. Circulating blood lymphocytes from two patients with neuronal ceroid-lipofuscinosis (NCL) were investigated by transmission electronmicroscopy. Ultrastructural examination showed two forms of intracytoplasmic single membrane-limited inclusions. Contents of the first inclusion form were arranged in five distinct patterns: (1) granules, (2) membranous formations, (3) paracrystalline forms, (4) alternating electron-dense/electron-lucent arrangements, and (5) admixtures of these components. These molecular morphologies suggest the usefulness of lymphocyte fine structure as a diagnostic tool in NCL. The second inclusion form contained cylinder-like structures. These structures are not specific for NCL and have been identified in other diseases."}
{"id": "PMID:205815", "title": "Polyneuropathy from inhalation of N2O cartridges through a whipped-cream dispenser.", "content": "A generalized toxic polyneuropathy was identified in a 23-year-old woman after excessive intentional inhalation of compressed N2O delivery from cartridges through a whipped-cream dispenser. The chronology of the patient's N2O abuse correlated clearly with two episodes of recurrent polyneuropathy. The toxic effects were limited to the nervous system, primarily involving the peripheral nerves, although some signs suggested a possible effect on the cerebellum or its connections. The findings on sural nerve biopsy were nonspecific, characterized principally by axonal degeneration. Gas chromatographic analysis of the N2O cartridges dispensed through the whipped-cream canister revealed an exposure to N2O and 26 other compounds. Three of these, trichloroethylene, toluene, and phenol, are known neurotoxins.", "contents": "Polyneuropathy from inhalation of N2O cartridges through a whipped-cream dispenser. A generalized toxic polyneuropathy was identified in a 23-year-old woman after excessive intentional inhalation of compressed N2O delivery from cartridges through a whipped-cream dispenser. The chronology of the patient's N2O abuse correlated clearly with two episodes of recurrent polyneuropathy. The toxic effects were limited to the nervous system, primarily involving the peripheral nerves, although some signs suggested a possible effect on the cerebellum or its connections. The findings on sural nerve biopsy were nonspecific, characterized principally by axonal degeneration. Gas chromatographic analysis of the N2O cartridges dispensed through the whipped-cream canister revealed an exposure to N2O and 26 other compounds. Three of these, trichloroethylene, toluene, and phenol, are known neurotoxins."}
{"id": "PMID:205816", "title": "Neuropathy following abuse of nitrous oxide.", "content": "A disabling peripheral neuropathy, mainly sensory, developed in three health workers who habitually abused nitrous oxide. The distinctive clinical picture included patterns of numbness that were radicular rather than purely distal, and a \"reverse\" Lhermitte sign, in the absence of signs of spinal cord involvement. Nerve conduction studies suggested an axonal rather than demyelinative neuropathy. The neurologic disorder improved slowly when the patients abstained from further nitrous oxide abuse.", "contents": "Neuropathy following abuse of nitrous oxide. A disabling peripheral neuropathy, mainly sensory, developed in three health workers who habitually abused nitrous oxide. The distinctive clinical picture included patterns of numbness that were radicular rather than purely distal, and a \"reverse\" Lhermitte sign, in the absence of signs of spinal cord involvement. Nerve conduction studies suggested an axonal rather than demyelinative neuropathy. The neurologic disorder improved slowly when the patients abstained from further nitrous oxide abuse."}
{"id": "PMID:205819", "title": "Differential maternal-fetal response to androgenizing luteoma or hyperreactio luteinalis.", "content": "Lacl of masculinization in female infants whose virilized mothers have h. luteinalis is in contrast to the common finding of fetal masculinization when maternal virilization occurs with luteoma of pregnancy. From the data at hand, this variation in fetal response cannot be explained by differences in the quantity of androgen production nor by the stage of pregnancy when maternal virilization becomes evident. Steroid analysis from cases of h. luteinalis suggests that the placenta may serve as an androgen barrier by aromatizing steroids before they reach the fetus. Testosterone conversion by the placenta of an anencephalic fetus confirms that conversion to estrogens occurs even without significant fetal adrenal activity. Understanding of the breakdown of this mechanism, with resultant fetal masculinization, will require careful evaluation of the steroid milieu in conditions like luteoma in which fetal masculinization often occurs. Both cystic and solid ovarian hyperplasia are recognized as are complications of pregnancy which require proper identification and conservative management. The significant difference in patients at risk for luteoma and h. luteinalis and the pathological and hormonal differences clearly indicate that these are distinct and separate entities.", "contents": "Differential maternal-fetal response to androgenizing luteoma or hyperreactio luteinalis. Lacl of masculinization in female infants whose virilized mothers have h. luteinalis is in contrast to the common finding of fetal masculinization when maternal virilization occurs with luteoma of pregnancy. From the data at hand, this variation in fetal response cannot be explained by differences in the quantity of androgen production nor by the stage of pregnancy when maternal virilization becomes evident. Steroid analysis from cases of h. luteinalis suggests that the placenta may serve as an androgen barrier by aromatizing steroids before they reach the fetus. Testosterone conversion by the placenta of an anencephalic fetus confirms that conversion to estrogens occurs even without significant fetal adrenal activity. Understanding of the breakdown of this mechanism, with resultant fetal masculinization, will require careful evaluation of the steroid milieu in conditions like luteoma in which fetal masculinization often occurs. Both cystic and solid ovarian hyperplasia are recognized as are complications of pregnancy which require proper identification and conservative management. The significant difference in patients at risk for luteoma and h. luteinalis and the pathological and hormonal differences clearly indicate that these are distinct and separate entities."}
{"id": "PMID:205820", "title": "[Creatine biosynthesis enzymes in the postnatal development of rats: the role of cyclo-3',5'-AMP and glucagon in the postnatal induction of liver guanidine acetate-N-methyltransferase].", "content": "The activity of enzymes of creatin biosynthesis in the rat liver and kidneys has been studied during the postnatal development. The activity of transamidinase of kidneys (E.C. 2.1.4.1.) increases gradually and linearly up to the 20th day after birth, then decreases on the 12th--25th days and increases again up to the level characteristic of the adult organism. The activity of guanidine acetate-N-methyl transferase (E.C. 2.1.1.2.) is rather high during the first days of postnatal development, then decreases and from the 15th day on increases again attaining the maximal level by the 23rd--25th day. The second period of the increase in the enzyme activity begins on the 29th--30th day of postnatal development. The results obtained suggest that the sharp increase of activity of guanidine acetate-N-methyl transferase of the rat liver during the early postnatal development is realized with the participation of cyclic 3',5'-AMP which appears to mediate the glucagon action.", "contents": "[Creatine biosynthesis enzymes in the postnatal development of rats: the role of cyclo-3',5'-AMP and glucagon in the postnatal induction of liver guanidine acetate-N-methyltransferase]. The activity of enzymes of creatin biosynthesis in the rat liver and kidneys has been studied during the postnatal development. The activity of transamidinase of kidneys (E.C. 2.1.4.1.) increases gradually and linearly up to the 20th day after birth, then decreases on the 12th--25th days and increases again up to the level characteristic of the adult organism. The activity of guanidine acetate-N-methyl transferase (E.C. 2.1.1.2.) is rather high during the first days of postnatal development, then decreases and from the 15th day on increases again attaining the maximal level by the 23rd--25th day. The second period of the increase in the enzyme activity begins on the 29th--30th day of postnatal development. The results obtained suggest that the sharp increase of activity of guanidine acetate-N-methyl transferase of the rat liver during the early postnatal development is realized with the participation of cyclic 3',5'-AMP which appears to mediate the glucagon action."}
{"id": "PMID:205821", "title": "Adenocarcinoma of the palate--diagnosis and management.", "content": "A case of adenocarcinoma of the palate has been presented. Emphasis has been placed on the surgical management and immediate postoperative care. Frequent postsurgical examination has been stressed to rule out evidence of recurrence or metastasis.", "contents": "Adenocarcinoma of the palate--diagnosis and management. A case of adenocarcinoma of the palate has been presented. Emphasis has been placed on the surgical management and immediate postoperative care. Frequent postsurgical examination has been stressed to rule out evidence of recurrence or metastasis."}
{"id": "PMID:205822", "title": "Cyst formation and cavitation in pulmonary metastases from Wilms' tumor. A report of two cases.", "content": "Two children with pulmonary metastases from Wilms' tumor are presented. In one case the lesions evolved into large cysts and in the other case cavitation occurred within two metastatic nodules. These are extremely rare complications of metastases from Wilms' tumor. The possible mechanisms are briefly discussed.", "contents": "Cyst formation and cavitation in pulmonary metastases from Wilms' tumor. A report of two cases. Two children with pulmonary metastases from Wilms' tumor are presented. In one case the lesions evolved into large cysts and in the other case cavitation occurred within two metastatic nodules. These are extremely rare complications of metastases from Wilms' tumor. The possible mechanisms are briefly discussed."}
{"id": "PMID:205823", "title": "Glycosaminoglycan synthesis by Wilms' tumor.", "content": "Wilms' tumor contains approximately 1 mg hyaluronic acid and approximately 0.3 mg sulfated glycosaminoglycan per g tissue. Minced tumor and cells cultured from the tumor incorporate labeled acetate and glucosamine into hyaluronic acid and sulfated glycosaminoglycans. A particulate enzyme preparation derived from the tumor catalyzed the transfer of GlcUA or GlcNAc from UDP-GlcUA or UDP-GlcNAc at a rate of approximately 20 nmol/hr/mg protein to produce high molecular weight hyaluronic acid chains. The urine and plasma of a Wilms' tumor patient contained approximately 20 mg hyaluronic acid and 8 mg sulfated glycosaminoglycan/100 ml, respectively. It appears that this higher than normal level of circulating glycosaminoglycan is synthesized by the Wilms' tumor.", "contents": "Glycosaminoglycan synthesis by Wilms' tumor. Wilms' tumor contains approximately 1 mg hyaluronic acid and approximately 0.3 mg sulfated glycosaminoglycan per g tissue. Minced tumor and cells cultured from the tumor incorporate labeled acetate and glucosamine into hyaluronic acid and sulfated glycosaminoglycans. A particulate enzyme preparation derived from the tumor catalyzed the transfer of GlcUA or GlcNAc from UDP-GlcUA or UDP-GlcNAc at a rate of approximately 20 nmol/hr/mg protein to produce high molecular weight hyaluronic acid chains. The urine and plasma of a Wilms' tumor patient contained approximately 20 mg hyaluronic acid and 8 mg sulfated glycosaminoglycan/100 ml, respectively. It appears that this higher than normal level of circulating glycosaminoglycan is synthesized by the Wilms' tumor."}
{"id": "PMID:205825", "title": "Effects of adrenocortical steroids and of adrenocorticotrophic hormone on (Na+-K+)-ATPase in immature cerebral cortex.", "content": "The effect of cortisol, methylprednisolone, and ACTH on (Na+-K+)-ATPase activity in developing cerebral cortex has been measured. Stimulation of (Na+-K+)-ATPase by these agents has been found in whole brain homogenates of kittens as early as age 8 days, and in whole homogenates and light microsomal fractions in young rats at 14 and 28 days. (Na+-K+)-ATPase activity in animals treated with corticosteroids or ACTH for 4 days was found to be 15--30% higher than activity in littermate controls. Brain potassium concentrations was increased in 14-day-old rats treated with methylprednisolone.", "contents": "Effects of adrenocortical steroids and of adrenocorticotrophic hormone on (Na+-K+)-ATPase in immature cerebral cortex. The effect of cortisol, methylprednisolone, and ACTH on (Na+-K+)-ATPase activity in developing cerebral cortex has been measured. Stimulation of (Na+-K+)-ATPase by these agents has been found in whole brain homogenates of kittens as early as age 8 days, and in whole homogenates and light microsomal fractions in young rats at 14 and 28 days. (Na+-K+)-ATPase activity in animals treated with corticosteroids or ACTH for 4 days was found to be 15--30% higher than activity in littermate controls. Brain potassium concentrations was increased in 14-day-old rats treated with methylprednisolone."}
{"id": "PMID:205826", "title": "The role of catecholamines in lung liquid absorption at birth.", "content": "We have examined the effect on lung liquid secretion of catecholamines infused in chronically catheterized fetal lambs in utero. Isoproterenol and epinephrine inhibited secretion, an effect which increased with gestation and, in fetuses near delivery, caused absorption of lung liquid. In 7 out of 8 experiments nor-epinephrine had no effect on secretion. This pattern of response and the fact that the inhibitory effect could be blocked by propranolol indicate a mode of action involving beta-adrenergic receptors.", "contents": "The role of catecholamines in lung liquid absorption at birth. We have examined the effect on lung liquid secretion of catecholamines infused in chronically catheterized fetal lambs in utero. Isoproterenol and epinephrine inhibited secretion, an effect which increased with gestation and, in fetuses near delivery, caused absorption of lung liquid. In 7 out of 8 experiments nor-epinephrine had no effect on secretion. This pattern of response and the fact that the inhibitory effect could be blocked by propranolol indicate a mode of action involving beta-adrenergic receptors."}
{"id": "PMID:205827", "title": "Nutrient intake and serum cholesterol level in normal children 6 to 16 years of age.", "content": "A study of 103 healthy, white schoolchildren who were between 6 and 16 years of age revealed no positive correlation between the level of serum cholesterol and the mean daily amount of total calories, cholesterol, fat, saturated fat, or sugar in the diet.", "contents": "Nutrient intake and serum cholesterol level in normal children 6 to 16 years of age. A study of 103 healthy, white schoolchildren who were between 6 and 16 years of age revealed no positive correlation between the level of serum cholesterol and the mean daily amount of total calories, cholesterol, fat, saturated fat, or sugar in the diet."}
{"id": "PMID:205829", "title": "A case of short rib polydactyly.", "content": "A patient with neonatal dwarfism had many characteristics of the Majewski syndrome, except for a cleft lip and abnormalities of internal organs. Absence of these anomalies and presence of more severe pathological changes in bone suggest either a wider spectrum for this disorder or a separate entity.", "contents": "A case of short rib polydactyly. A patient with neonatal dwarfism had many characteristics of the Majewski syndrome, except for a cleft lip and abnormalities of internal organs. Absence of these anomalies and presence of more severe pathological changes in bone suggest either a wider spectrum for this disorder or a separate entity."}
{"id": "PMID:205832", "title": "Sleep and memory: reproduction of syntactic structures previously evoked within REM sleep-related reports.", "content": "7 subjects, aged 19 to 25 yr., who evoked syntactic verbal material in the report made after awakening during REM sleep, were asked to reproduce it a few minutes later. No big differences had been obsered between the two recalls; all recalled verbal materials, many sentences and kernel-sentences reappeared. These results indicate a good consolidation of the material obtained after awakening during REM sleep.", "contents": "Sleep and memory: reproduction of syntactic structures previously evoked within REM sleep-related reports. 7 subjects, aged 19 to 25 yr., who evoked syntactic verbal material in the report made after awakening during REM sleep, were asked to reproduce it a few minutes later. No big differences had been obsered between the two recalls; all recalled verbal materials, many sentences and kernel-sentences reappeared. These results indicate a good consolidation of the material obtained after awakening during REM sleep."}
{"id": "PMID:205833", "title": "Psychophysiological correlates of the spontaneous K-complex.", "content": "A pilot study covering three nights and two studies were carried out to investigate the psychophysiological correlates of the spontaneous K-complex in relation to intense psychotherapy. The pilot study produced evidence that the K-complex was not consistent and stable within or across nights and that its variability might be sensitive to psycho-emotional influences. In the first major study 2 subjects were recorded non-consecutively over a 3-wk. period during experience of intensive therapy while in the second 6 subjects were studied before and after two therapeutic sessions. Results indicated that nights after therapy differed significantly from baseline nights and a significant interaction took place between subjects and therapy on one or more variables of the K-complex and several eye movement indices. Some relationship to length of time in therapy was also noted. These findings were interpreted to indicate a possible relationship between complete expression of feeling and the occurrence of phasic events in the sleeping EEG.", "contents": "Psychophysiological correlates of the spontaneous K-complex. A pilot study covering three nights and two studies were carried out to investigate the psychophysiological correlates of the spontaneous K-complex in relation to intense psychotherapy. The pilot study produced evidence that the K-complex was not consistent and stable within or across nights and that its variability might be sensitive to psycho-emotional influences. In the first major study 2 subjects were recorded non-consecutively over a 3-wk. period during experience of intensive therapy while in the second 6 subjects were studied before and after two therapeutic sessions. Results indicated that nights after therapy differed significantly from baseline nights and a significant interaction took place between subjects and therapy on one or more variables of the K-complex and several eye movement indices. Some relationship to length of time in therapy was also noted. These findings were interpreted to indicate a possible relationship between complete expression of feeling and the occurrence of phasic events in the sleeping EEG."}
{"id": "PMID:205835", "title": "[Diffuse polymorphous inclusions in a patient treated with perhexiline maleate (author's transl)].", "content": "Case report of polyneuritis and liver dysfunction induced by perhexiline maleate in a 64 years old male patient. The ultrastructural study of nerve, liver, muscle and skin biopsies shows polymorphous, membrane bound, often multilamellar, lysosome-like inclusions, the content of which is probably complex lipids. The histochemical study of liver reveals a lipid storage, consisting mainly of triglycerides and of smaller amount of phospholipids and free fatty acids, the pattern of which is abnormal. The biochemical study of nerve tissue shows a decrease of phospholipids levels and some qualitative disturbances in gangliosides. These changes, some of which are similar to those reported in amphiphilic drug intoxications, are prevalent in high lipid metabolism cells such as hepatic and Schwann cells.", "contents": "[Diffuse polymorphous inclusions in a patient treated with perhexiline maleate (author's transl)]. Case report of polyneuritis and liver dysfunction induced by perhexiline maleate in a 64 years old male patient. The ultrastructural study of nerve, liver, muscle and skin biopsies shows polymorphous, membrane bound, often multilamellar, lysosome-like inclusions, the content of which is probably complex lipids. The histochemical study of liver reveals a lipid storage, consisting mainly of triglycerides and of smaller amount of phospholipids and free fatty acids, the pattern of which is abnormal. The biochemical study of nerve tissue shows a decrease of phospholipids levels and some qualitative disturbances in gangliosides. These changes, some of which are similar to those reported in amphiphilic drug intoxications, are prevalent in high lipid metabolism cells such as hepatic and Schwann cells."}
{"id": "PMID:205837", "title": "Characterization of N6, O2-dimethyladenosine from nuclear RNA of Novikoff hepatoma.", "content": "A modified nucleoside was isolated from low molecular weight nuclear RNA of Novikoff hepatoma, the nucleotide sequence of which was reported earlier. The structure of this novel nucleoside was shown to be N6, O2'-dimethyladenosine (m6Am) by mass spectrometry of its trimethylsilyl derivative and by comparison with the mass spectra of N6- and O-2' monmethyl model compounds. The complete characterization was carried out using 0.04 A260 units (2 microgram) of m6Am.", "contents": "Characterization of N6, O2-dimethyladenosine from nuclear RNA of Novikoff hepatoma. A modified nucleoside was isolated from low molecular weight nuclear RNA of Novikoff hepatoma, the nucleotide sequence of which was reported earlier. The structure of this novel nucleoside was shown to be N6, O2'-dimethyladenosine (m6Am) by mass spectrometry of its trimethylsilyl derivative and by comparison with the mass spectra of N6- and O-2' monmethyl model compounds. The complete characterization was carried out using 0.04 A260 units (2 microgram) of m6Am."}
{"id": "PMID:205838", "title": "Polynucleotide kinase from a T4 mutant which lacks the 3' phosphatase activity.", "content": "Polynucleotide kinase from E. coli infected with the PseT 1 mutant of bacteriophage T4 has been isolated. The PseT 1 enzyme purifies similarly to normal polynucleotide kinase and effectively transfers the gamma phosphate of ATP to the 5' terminal hydroxyl of DNA and RNA. The PseT 1 and normal enzymes require similar magnesium ion concentrations, have the same pH optima and are both inhibited by inorganic phosphate. However, the PseT 1 enzyme is totally lacking the 3' phosphatase activity associated with normal  polynucleotide kinase. The PseT 1 enzyme is a useful tool for the preparation of oligonucleotides with 3' and 5' terminal phosphates for use as susbstrates for RNA ligase.", "contents": "Polynucleotide kinase from a T4 mutant which lacks the 3' phosphatase activity. Polynucleotide kinase from E. coli infected with the PseT 1 mutant of bacteriophage T4 has been isolated. The PseT 1 enzyme purifies similarly to normal polynucleotide kinase and effectively transfers the gamma phosphate of ATP to the 5' terminal hydroxyl of DNA and RNA. The PseT 1 and normal enzymes require similar magnesium ion concentrations, have the same pH optima and are both inhibited by inorganic phosphate. However, the PseT 1 enzyme is totally lacking the 3' phosphatase activity associated with normal  polynucleotide kinase. The PseT 1 enzyme is a useful tool for the preparation of oligonucleotides with 3' and 5' terminal phosphates for use as susbstrates for RNA ligase."}
{"id": "PMID:205839", "title": "Properies of tRNAPhe from yeast carrying a spin label on the 3'-terminal. Interaction with yeast phenylalanyl-tRNA Synthetase and elongation factor Tu from Escherichia coli.", "content": "The 2-thioketo function of tRNAPhe-C-s2C-A in which the penultimate cytidine residue is replaced by 20thiocytidine can serve as a site of specific attachment of spin label. By alkylation of tRNAPhe-C-s2C-A with iodoacetamide or its spin label derivatives tRNAPhe-C-(acm)s2C-A or tRNAPheC-(SL)s2C-A are formed. The enzymatic phenylalanylation of these tRNAsPhe revealed that the 2-position of the penultimate cytidine can be modified without impairing this enzymatic reaction but there exists a sterical limitation for the subsituent on this position beyond which the tRNAPhe:phenylalanyl-tRNA synthetase recognition is not possible. Both Phe-tRNAPhe-C-(acm)s2C-A as well as Phe-tRNAPhe-C(SL)s2C-A form ternary complexes with EF-Tu.GTP. The part of the 3'-terminus of tRNAPhe where the additional substituents are attached is therefore not involved in the interaction with this elongation factor. This could be also demonstrated by ESR measurements of spin labelled tRNAsPhe. The correlation times, tauc, for tRNAPhe-C-(SL)s2C-A, Phe-tRNAPhe-C-(SL)s2C-A and Phe-tRNAPhe-C-(SL)s2C-A.EF-Tu:GTP are essentially identical indicating that the structure of the 3'-end of tRNAPhe is not influenced significantly by aminoacylation or ternary complex formation.", "contents": "Properies of tRNAPhe from yeast carrying a spin label on the 3'-terminal. Interaction with yeast phenylalanyl-tRNA Synthetase and elongation factor Tu from Escherichia coli. The 2-thioketo function of tRNAPhe-C-s2C-A in which the penultimate cytidine residue is replaced by 20thiocytidine can serve as a site of specific attachment of spin label. By alkylation of tRNAPhe-C-s2C-A with iodoacetamide or its spin label derivatives tRNAPhe-C-(acm)s2C-A or tRNAPheC-(SL)s2C-A are formed. The enzymatic phenylalanylation of these tRNAsPhe revealed that the 2-position of the penultimate cytidine can be modified without impairing this enzymatic reaction but there exists a sterical limitation for the subsituent on this position beyond which the tRNAPhe:phenylalanyl-tRNA synthetase recognition is not possible. Both Phe-tRNAPhe-C-(acm)s2C-A as well as Phe-tRNAPhe-C(SL)s2C-A form ternary complexes with EF-Tu.GTP. The part of the 3'-terminus of tRNAPhe where the additional substituents are attached is therefore not involved in the interaction with this elongation factor. This could be also demonstrated by ESR measurements of spin labelled tRNAsPhe. The correlation times, tauc, for tRNAPhe-C-(SL)s2C-A, Phe-tRNAPhe-C-(SL)s2C-A and Phe-tRNAPhe-C-(SL)s2C-A.EF-Tu:GTP are essentially identical indicating that the structure of the 3'-end of tRNAPhe is not influenced significantly by aminoacylation or ternary complex formation."}
{"id": "PMID:205848", "title": "Effect of freezing on incidence and levels of Clostridium perfringens in mechanically deboned chicken meat.", "content": "Paucity of information about the effect of plant practices on microbiological condition of comminuted chicken meat prompted this investigation. Commercially deboned chicken backs and necks were analyzed for levels of aerobic organisms, incidence and levels of Clostridium perfringens vegetative cells and spores before and after 4-6 weeks at -23 degrees C. Initially vegetative cells were isolated more frequently than spores. Frozen storage significantly reduced incidence and levels of vegetative cells and spores but did not affect levels of aerobic organisms. After frozen storage (a common industrial practice), with good food handling practices, C. perfringens should pose no undue hazard when comminuted chicken meat is incorporated into other food products.", "contents": "Effect of freezing on incidence and levels of Clostridium perfringens in mechanically deboned chicken meat. Paucity of information about the effect of plant practices on microbiological condition of comminuted chicken meat prompted this investigation. Commercially deboned chicken backs and necks were analyzed for levels of aerobic organisms, incidence and levels of Clostridium perfringens vegetative cells and spores before and after 4-6 weeks at -23 degrees C. Initially vegetative cells were isolated more frequently than spores. Frozen storage significantly reduced incidence and levels of vegetative cells and spores but did not affect levels of aerobic organisms. After frozen storage (a common industrial practice), with good food handling practices, C. perfringens should pose no undue hazard when comminuted chicken meat is incorporated into other food products."}
{"id": "PMID:205849", "title": "Immunosuppression in chickens by passive transfer of preparations of specific immunoglobulins.", "content": "The immunosuppressive effects of passive transfers of specific immunoglobulin preparations obtained from immune or hyperimmune sera were evaluated in chickens which were challenged with sheep red blood cells. The data indicate that IgY, fractionated from immune sera, and IgY and IgM, fractionated from hyperimmune sera, when passively administered at the doses employed in this study resulted in antibody-mediated suppression.", "contents": "Immunosuppression in chickens by passive transfer of preparations of specific immunoglobulins. The immunosuppressive effects of passive transfers of specific immunoglobulin preparations obtained from immune or hyperimmune sera were evaluated in chickens which were challenged with sheep red blood cells. The data indicate that IgY, fractionated from immune sera, and IgY and IgM, fractionated from hyperimmune sera, when passively administered at the doses employed in this study resulted in antibody-mediated suppression."}
{"id": "PMID:205850", "title": "Oncogenicity of the C-type virus HL-23V in marmosets and characterization of virus isolated from an HL-23V-induced marmoset tumor: comparison with simian sarcoma virus type 1.", "content": "Dog thymus cells chronically infected with HL-23V, a C-type virus isolated from human acute myelogenous leukemia cells, produced both transforming and nontransforming virus indistinguishable from simian sarcoma virus type 1 (SSV-1/SSAV-1) and induced fibromas in newborn marmosets. All inoculated marmosets developed anti-HL-23V antibodies. A cell line established from a tumor biopsy produced transforming virus identical to SSV-1 and HL-23V at early passages. However, at later passages the cell line and a cell line established from residual tumor tissue removed at autopsy, produced virus which was neutralized only at low dilutions of anti-SSV-1 serum (1:32) relative to SSV-1 (1:1,024). This virus (BFV) was also distinguished from SSV-1 and HL-23V by XC tests, and by membrane immunofluorescence and serum cytotoxicity tests.", "contents": "Oncogenicity of the C-type virus HL-23V in marmosets and characterization of virus isolated from an HL-23V-induced marmoset tumor: comparison with simian sarcoma virus type 1. Dog thymus cells chronically infected with HL-23V, a C-type virus isolated from human acute myelogenous leukemia cells, produced both transforming and nontransforming virus indistinguishable from simian sarcoma virus type 1 (SSV-1/SSAV-1) and induced fibromas in newborn marmosets. All inoculated marmosets developed anti-HL-23V antibodies. A cell line established from a tumor biopsy produced transforming virus identical to SSV-1 and HL-23V at early passages. However, at later passages the cell line and a cell line established from residual tumor tissue removed at autopsy, produced virus which was neutralized only at low dilutions of anti-SSV-1 serum (1:32) relative to SSV-1 (1:1,024). This virus (BFV) was also distinguished from SSV-1 and HL-23V by XC tests, and by membrane immunofluorescence and serum cytotoxicity tests."}
{"id": "PMID:205846", "title": "The influence of dibutyryl cGMP on the rabbit auricle.", "content": "Dibutyryl cGMP, like acetylcholine, shortens and reduces repolarization and overshoot of the action potential, slightly hyperpolarizes the cell and decreases the force of the contraction in the atrial working muscle. It suggests that cGMP may mediate the action of acetylcholine in the atrial working fibres.", "contents": "The influence of dibutyryl cGMP on the rabbit auricle. Dibutyryl cGMP, like acetylcholine, shortens and reduces repolarization and overshoot of the action potential, slightly hyperpolarizes the cell and decreases the force of the contraction in the atrial working muscle. It suggests that cGMP may mediate the action of acetylcholine in the atrial working fibres."}
{"id": "PMID:205851", "title": "Studies with the baboon endogenous virus and its pseudotype of murine sarcoma virus in marmosets.", "content": "Three marmoset species (Saguinus oedipus oedipus, S. fuscicollis, Callithrix jacchus) failed to show evidence of infection or disease following inoculation of baboon endogenous type-C virus (BaEV). Cells infected with a Kirsten murine sarcoma-BaEV pseudotype (MSV[BaEV]) produced a progressive fibrosarcoma in S. o. oedipus and tumors in S. fuscicollis and C. jacchus which regressed. Tumor formation is believed to be due to growth of inoculated, virus-infected cells and not transformation of marmoset cells. S. o. oedipus showed the best serum neutralizing antibody response to BaEV and MSV(BaEV), S. fuscicollis a moderate response and C. jacchus no response.", "contents": "Studies with the baboon endogenous virus and its pseudotype of murine sarcoma virus in marmosets. Three marmoset species (Saguinus oedipus oedipus, S. fuscicollis, Callithrix jacchus) failed to show evidence of infection or disease following inoculation of baboon endogenous type-C virus (BaEV). Cells infected with a Kirsten murine sarcoma-BaEV pseudotype (MSV[BaEV]) produced a progressive fibrosarcoma in S. o. oedipus and tumors in S. fuscicollis and C. jacchus which regressed. Tumor formation is believed to be due to growth of inoculated, virus-infected cells and not transformation of marmoset cells. S. o. oedipus showed the best serum neutralizing antibody response to BaEV and MSV(BaEV), S. fuscicollis a moderate response and C. jacchus no response."}
{"id": "PMID:205852", "title": "Differences in expression of surface marker characteristics on Epstein-Barr virus-transformed human and simian lymphoid cell lines.", "content": "Human lymphoblastoid cell lines transformed in vitro by the Epstein-Barr virus (EBV) had receptors for fixed complement detectable by a rosette test. EBV transformed cells derived from cotton-topped marmoset leukocytes did not express this receptor. Evidence is presented that both human and marmoset cell lines arose from precursor cells which have complement receptors. Our findings suggest that transformation of marmoset leukocytes by EBV results in the loss of a differentiated surface marker.", "contents": "Differences in expression of surface marker characteristics on Epstein-Barr virus-transformed human and simian lymphoid cell lines. Human lymphoblastoid cell lines transformed in vitro by the Epstein-Barr virus (EBV) had receptors for fixed complement detectable by a rosette test. EBV transformed cells derived from cotton-topped marmoset leukocytes did not express this receptor. Evidence is presented that both human and marmoset cell lines arose from precursor cells which have complement receptors. Our findings suggest that transformation of marmoset leukocytes by EBV results in the loss of a differentiated surface marker."}
{"id": "PMID:205853", "title": "Characteristics of cell lines established from Epstein-Barr virus induced marmoset tumors.", "content": "The inoculation of a cotton-topped marmoset with B95-8 strain of EBV resulted in the induction of a multifocal lymphoma and lymphoblastoid cell lines were established from liver, spleen and mesenteric lymph node tumors. The cell lines were remarkably similar to each other with respect to the presence of EBV and its expression, the surface properties of the cells and their stability, and the functional products of the cells. Karyotypic examination of the cell lines revealed the common loss of a single chromosome. The slight differences noted in karyotypes suggest some divergence from a tumor stem cell and imply a clonal origin. Thus, EBV-induced lymphomas in cotton-topped marmosets resemble Burkitt's lymphoma in man.", "contents": "Characteristics of cell lines established from Epstein-Barr virus induced marmoset tumors. The inoculation of a cotton-topped marmoset with B95-8 strain of EBV resulted in the induction of a multifocal lymphoma and lymphoblastoid cell lines were established from liver, spleen and mesenteric lymph node tumors. The cell lines were remarkably similar to each other with respect to the presence of EBV and its expression, the surface properties of the cells and their stability, and the functional products of the cells. Karyotypic examination of the cell lines revealed the common loss of a single chromosome. The slight differences noted in karyotypes suggest some divergence from a tumor stem cell and imply a clonal origin. Thus, EBV-induced lymphomas in cotton-topped marmosets resemble Burkitt's lymphoma in man."}
{"id": "PMID:205854", "title": "Susceptibility of marmosets to Epstein-Barr virus-like baboon herpesviruses.", "content": "Epstein-Barr virus (EBV)-like herpeviruses, strains of Herpesvirus papio (HVP), have recently been isolated from lymphomatous (HVP-L) and from normal baboons (HVP-N). Both HVP isolates infect some species of marmosets, HVP-L inoculated adult animals develop a mild to severe and sometimes fatal lymphoproliferative disease whereas newborn marmosets of the same species do not develop a measureable disease after inoculation with HVP-l. HVP-N infects adult marmosets but does not cause disease.", "contents": "Susceptibility of marmosets to Epstein-Barr virus-like baboon herpesviruses. Epstein-Barr virus (EBV)-like herpeviruses, strains of Herpesvirus papio (HVP), have recently been isolated from lymphomatous (HVP-L) and from normal baboons (HVP-N). Both HVP isolates infect some species of marmosets, HVP-L inoculated adult animals develop a mild to severe and sometimes fatal lymphoproliferative disease whereas newborn marmosets of the same species do not develop a measureable disease after inoculation with HVP-l. HVP-N infects adult marmosets but does not cause disease."}
{"id": "PMID:205855", "title": "Spontaneous infectious diseases of marmosets.", "content": "The various species of marmosets are susceptible to a wide variety of infectious agents of which only a few have been fully characterized. Little is known concerning spontaneous disease in their natural habitat, and often deaths in the laboratory go unexplained. In captivity, Herpesvirus-T infection appears to be the most important viral infection, but serious disease may also follow infection with measles virus (rubeola) and an unidentified paramyxovirus. Bacterial diseases are multiple, but rarely occur as epizootics. Various species of Salmonella, Yersinia, Klebsiella, and Diplococcus are among the more frequent pathogens. Mycoses and parasitic infections are also numerous, but most do not result in major losses.", "contents": "Spontaneous infectious diseases of marmosets. The various species of marmosets are susceptible to a wide variety of infectious agents of which only a few have been fully characterized. Little is known concerning spontaneous disease in their natural habitat, and often deaths in the laboratory go unexplained. In captivity, Herpesvirus-T infection appears to be the most important viral infection, but serious disease may also follow infection with measles virus (rubeola) and an unidentified paramyxovirus. Bacterial diseases are multiple, but rarely occur as epizootics. Various species of Salmonella, Yersinia, Klebsiella, and Diplococcus are among the more frequent pathogens. Mycoses and parasitic infections are also numerous, but most do not result in major losses."}
{"id": "PMID:205856", "title": "Transfer factor and its protective effect against herpesvirus infections of marmosets.", "content": "Using skin test response and lymphocyte blastogenesis as indicators of cell-mediated immunity, we have been able to demonstrate in vivo transfer of cell-mediated immunity to marmosets both with dialyzable transfer factor (TFd) prepared from a human donor and transfer factor (TF) from baboon whole cell lysates. We were able to protect marmosets with TFd from fatal Herpesvirus hominis type 1 (HVH-1) disease. When TFd was administered prior to challenge with HVH-1, 50% of the marmosets survived. Of the untreated control animals and those first treated on day 0 or postinfection, 100% succumbed to disseminated HVH-1 disease. In addition, when TF prepared from TFd-treated marmosets which had survived HVH-1 disease, was given to other marmosets, it conferred protection from subsequent HVH-1 challenge.", "contents": "Transfer factor and its protective effect against herpesvirus infections of marmosets. Using skin test response and lymphocyte blastogenesis as indicators of cell-mediated immunity, we have been able to demonstrate in vivo transfer of cell-mediated immunity to marmosets both with dialyzable transfer factor (TFd) prepared from a human donor and transfer factor (TF) from baboon whole cell lysates. We were able to protect marmosets with TFd from fatal Herpesvirus hominis type 1 (HVH-1) disease. When TFd was administered prior to challenge with HVH-1, 50% of the marmosets survived. Of the untreated control animals and those first treated on day 0 or postinfection, 100% succumbed to disseminated HVH-1 disease. In addition, when TF prepared from TFd-treated marmosets which had survived HVH-1 disease, was given to other marmosets, it conferred protection from subsequent HVH-1 challenge."}
{"id": "PMID:205858", "title": "Tests in rufiventer and other marmosets of susceptibility to human hepatitis A virus.", "content": "The rufiventer marmoset proved equally satisfactory to S. mystax for studies of human hepatitis A virus. C. jacchus, C. argentata, S. weddelli, and S. oedipomidas oedipus were not satisfactory. Livers of rufiventer marmosets produced satisfactory CR326 strain hepatitis A antigen for immune adherence tests both in amount and specificity. Rufiventer marmosets infected with human hepatitis A virus showed enzyme elevations and high titers of viral antigen in their livers as early as seven days after viral inoculation, indicating that a primary viral infection can cause hepatitis without need for a secondary autoimmune response to liver tissue.", "contents": "Tests in rufiventer and other marmosets of susceptibility to human hepatitis A virus. The rufiventer marmoset proved equally satisfactory to S. mystax for studies of human hepatitis A virus. C. jacchus, C. argentata, S. weddelli, and S. oedipomidas oedipus were not satisfactory. Livers of rufiventer marmosets produced satisfactory CR326 strain hepatitis A antigen for immune adherence tests both in amount and specificity. Rufiventer marmosets infected with human hepatitis A virus showed enzyme elevations and high titers of viral antigen in their livers as early as seven days after viral inoculation, indicating that a primary viral infection can cause hepatitis without need for a secondary autoimmune response to liver tissue."}
{"id": "PMID:205859", "title": "Experimental infection of marmosets with hepatitis A virus.", "content": "Saguinus mystax marmosets were experimentally infected with two strains of human hepatitis A virus. One of these strains of HAV was successfully subpassaged in this species of marmosets. In another experiment, the 1.32 and 1.41 g/cm3 buoyant density species of HAV derived from an infected chimpanzee stool were shown to be infectious in three species of marmosets. The value of the marmoset as an experimental model for hepatitis A infection was demonstrated by these studies.", "contents": "Experimental infection of marmosets with hepatitis A virus. Saguinus mystax marmosets were experimentally infected with two strains of human hepatitis A virus. One of these strains of HAV was successfully subpassaged in this species of marmosets. In another experiment, the 1.32 and 1.41 g/cm3 buoyant density species of HAV derived from an infected chimpanzee stool were shown to be infectious in three species of marmosets. The value of the marmoset as an experimental model for hepatitis A infection was demonstrated by these studies."}
{"id": "PMID:205860", "title": "Overview of viral oncology studies in Saguinus and Callithrix species.", "content": "Marmoset monkeys are highly susceptible to tumor induction by type C sarcoma viruses and primate lymphotropic herpeviruses. Six experimental models were reviewed, three sarcoma models induced by Rous, feline or simian sarcoma viruses and three models of lymphoproliferative disease induced by Herpevirus saimiri, H. ateles or Epstein-Barr virus. Relative susceptibility of cotton-topped (Saguinus oedipus oedipus), white-lipped (S. nigricollis, S. fuscicollis subspecies) and commone (Callithrix jacchus jacchus) marmosets to the different viruses was compared.", "contents": "Overview of viral oncology studies in Saguinus and Callithrix species. Marmoset monkeys are highly susceptible to tumor induction by type C sarcoma viruses and primate lymphotropic herpeviruses. Six experimental models were reviewed, three sarcoma models induced by Rous, feline or simian sarcoma viruses and three models of lymphoproliferative disease induced by Herpevirus saimiri, H. ateles or Epstein-Barr virus. Relative susceptibility of cotton-topped (Saguinus oedipus oedipus), white-lipped (S. nigricollis, S. fuscicollis subspecies) and commone (Callithrix jacchus jacchus) marmosets to the different viruses was compared."}
{"id": "PMID:205864", "title": "Species-specific cellular DNA-binding proteins expressed in mouse cells transformed by chemical carcinogens.", "content": "Mouse cells transformed by DNA and RNA tumor viruses and by chemical carcinogens have been examined for the presence of specific DNA-binding proteins by DNA-cellulose chromatography. Using mouse DNA-cellulose we have obtained single-stranded DNA-binding proteins from two clones transformed by chemical carcinogens. Simian virus 40 transformants also have a DNA-binding protein [the tumor (T) antigen] that binds to mouse and human DNA with comparable affinity. Mouse sarcoma virus-transformed cells and two other chemically transformed clones showed no difference in DNA-binding protein pattern compared to the untransformed parental cell. The DNA-binding proteins isolated from the chemically transformed cell clones are between 25,000 and 30,000 daltons by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. These cellular \"T proteins\" bind to the homologous mouse cellular DNA with a higher affinity than to heterologous human cellular DNA.", "contents": "Species-specific cellular DNA-binding proteins expressed in mouse cells transformed by chemical carcinogens. Mouse cells transformed by DNA and RNA tumor viruses and by chemical carcinogens have been examined for the presence of specific DNA-binding proteins by DNA-cellulose chromatography. Using mouse DNA-cellulose we have obtained single-stranded DNA-binding proteins from two clones transformed by chemical carcinogens. Simian virus 40 transformants also have a DNA-binding protein [the tumor (T) antigen] that binds to mouse and human DNA with comparable affinity. Mouse sarcoma virus-transformed cells and two other chemically transformed clones showed no difference in DNA-binding protein pattern compared to the untransformed parental cell. The DNA-binding proteins isolated from the chemically transformed cell clones are between 25,000 and 30,000 daltons by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. These cellular \"T proteins\" bind to the homologous mouse cellular DNA with a higher affinity than to heterologous human cellular DNA."}
{"id": "PMID:205861", "title": "[In vitro thyroid hormone reception by the adenohypophysis and hypothalamus of male rats of different ages].", "content": "In studying the thyroid hormone binding with the water-salt extracts of the adenohypophysis and the hypothalamus of male rats after Schreiber it was shown that with ageing there occurred in the adenohypophysis a redistribution of T4 and T3 binding in the direction fo an increase of the T4/T3 coefficient, and a reduction of the relative T3 binding, the latter bordering with the significant one. Some reduction of the T4/T3 coefficient, both in comparison with the rest of the tissues under study and in age aspect, was peculiar to the posterior hypothalamus. In the rats-tumour-carriers some changes in the thyroid hormone binding (reduction of the T4/T3 index in the posterior hypothalamus and its sufficiently high values in the adenohypophysis and the anterior hypothalamus) were similar to those observed in normal and ageing rats.", "contents": "[In vitro thyroid hormone reception by the adenohypophysis and hypothalamus of male rats of different ages]. In studying the thyroid hormone binding with the water-salt extracts of the adenohypophysis and the hypothalamus of male rats after Schreiber it was shown that with ageing there occurred in the adenohypophysis a redistribution of T4 and T3 binding in the direction fo an increase of the T4/T3 coefficient, and a reduction of the relative T3 binding, the latter bordering with the significant one. Some reduction of the T4/T3 coefficient, both in comparison with the rest of the tissues under study and in age aspect, was peculiar to the posterior hypothalamus. In the rats-tumour-carriers some changes in the thyroid hormone binding (reduction of the T4/T3 index in the posterior hypothalamus and its sufficiently high values in the adenohypophysis and the anterior hypothalamus) were similar to those observed in normal and ageing rats."}
{"id": "PMID:205865", "title": "Insulin and epidermal growth factor-urogastrone: affinity crosslinking to specific binding sites in rat liver membranes.", "content": "Both insulin and human epidermal growth factor-urogastrone (EGF/URO) can be covalently linked to specific rat liver membrane binding sites by glutaraldehyde coupling followed by sodium borohydride reduction to yield affinity-labeled membrane constituents sufficiently stable for solubilization and further analysis by various techniques. Solubilization of membranes covalently labeled with (125)I-labeled insulin yields a component with chromatographic properties identical to those of a soluble insulin receptor characterized in previous studies. A second soluble insulin-binding component that is not revealed by the affinity-labeling method and that has not yet been reported can also be detected. Membranes similarly labeled with (125)I-labeled EGF/URO yield one major and two minor ligand-specific soluble (Triton X-100) affinity-labeled components, as detected by chromatography on Sepharose 6B. Further analysis of the EGF/URO-labeled components by affinity chromatography on concanavalin A-Sepharose, by disc gel electrophoresis, and by enzymatic digestion suggests that the major specific binding component for EGF/URO in liver membranes is a glycoprotein subunit of approximately 100,000 daltons that possesses a 20,000-dalton portion inaccessible to proteolytic cleavage when the subunit is anchored in the membrane. The affinity labeling approach described should prove of use for the study of other polypeptide receptors that, like the EGF/URO receptor, lose their ligand recognition property subsequent to membrane solubilization.", "contents": "Insulin and epidermal growth factor-urogastrone: affinity crosslinking to specific binding sites in rat liver membranes. Both insulin and human epidermal growth factor-urogastrone (EGF/URO) can be covalently linked to specific rat liver membrane binding sites by glutaraldehyde coupling followed by sodium borohydride reduction to yield affinity-labeled membrane constituents sufficiently stable for solubilization and further analysis by various techniques. Solubilization of membranes covalently labeled with (125)I-labeled insulin yields a component with chromatographic properties identical to those of a soluble insulin receptor characterized in previous studies. A second soluble insulin-binding component that is not revealed by the affinity-labeling method and that has not yet been reported can also be detected. Membranes similarly labeled with (125)I-labeled EGF/URO yield one major and two minor ligand-specific soluble (Triton X-100) affinity-labeled components, as detected by chromatography on Sepharose 6B. Further analysis of the EGF/URO-labeled components by affinity chromatography on concanavalin A-Sepharose, by disc gel electrophoresis, and by enzymatic digestion suggests that the major specific binding component for EGF/URO in liver membranes is a glycoprotein subunit of approximately 100,000 daltons that possesses a 20,000-dalton portion inaccessible to proteolytic cleavage when the subunit is anchored in the membrane. The affinity labeling approach described should prove of use for the study of other polypeptide receptors that, like the EGF/URO receptor, lose their ligand recognition property subsequent to membrane solubilization."}
{"id": "PMID:205862", "title": "[Effect of large doses of reserpine on the hypothalamo-hypophyseal-adrenal system in Itsenko-Cushing's disease].", "content": "The results of study of the hypothalamo-hypophysio-adrenal system in patients with Itsenko-Cushing's disease under the influence of high reserpine doses are presented. An increase of plasma ACTH and cortizol level and disturbance of the 24-hour rhythm of their secretion was noted in the patients. High reserpine doses led to the fall of ACTH and cortizol secretion, without any normalization of their secretion rhythm in the course of 24 hours. A test with metopyron carried out before and after the reserpine prescription pointed to the increase of the ACTH reserve under the influence of high reserpine doses.", "contents": "[Effect of large doses of reserpine on the hypothalamo-hypophyseal-adrenal system in Itsenko-Cushing's disease]. The results of study of the hypothalamo-hypophysio-adrenal system in patients with Itsenko-Cushing's disease under the influence of high reserpine doses are presented. An increase of plasma ACTH and cortizol level and disturbance of the 24-hour rhythm of their secretion was noted in the patients. High reserpine doses led to the fall of ACTH and cortizol secretion, without any normalization of their secretion rhythm in the course of 24 hours. A test with metopyron carried out before and after the reserpine prescription pointed to the increase of the ACTH reserve under the influence of high reserpine doses."}
{"id": "PMID:205863", "title": "[Mechanisms of neuromuscular transmission disorder in rats with alloxan diabetes].", "content": "A microelectrode intracellular leading off of the postsynaptic potentials of isolated skeletal muscles was carried out in rats with alloxan diabetes of short duration (1--5 weeks), but manifest (blood sugar level from 150 to 350 mg%). A significant disturbance of the neuro-muscular synaptic transmission in this case was wholly caused by the reduction of the excitatory capacity of the presynaptic terminals. There was seen a reduction of the frequency of the miniature potentials of end plates (PEP), and a reduction of quant PEP composition. A distinct reduction of the intensity of the mediator synthesis, without any significant suppression of the fractional acetylcholine secretion was revealed in determination of the dynamic characteristics of the mediator transformations. This served as the cause of a deficiency of the fraction of a mediator ready for use in the animals suffering from diabetes.", "contents": "[Mechanisms of neuromuscular transmission disorder in rats with alloxan diabetes]. A microelectrode intracellular leading off of the postsynaptic potentials of isolated skeletal muscles was carried out in rats with alloxan diabetes of short duration (1--5 weeks), but manifest (blood sugar level from 150 to 350 mg%). A significant disturbance of the neuro-muscular synaptic transmission in this case was wholly caused by the reduction of the excitatory capacity of the presynaptic terminals. There was seen a reduction of the frequency of the miniature potentials of end plates (PEP), and a reduction of quant PEP composition. A distinct reduction of the intensity of the mediator synthesis, without any significant suppression of the fractional acetylcholine secretion was revealed in determination of the dynamic characteristics of the mediator transformations. This served as the cause of a deficiency of the fraction of a mediator ready for use in the animals suffering from diabetes."}
{"id": "PMID:205866", "title": "A simple model of DNA superhelices in solution.", "content": "Closed circular DNA molecules in aqueous solution take the form of interwound superhelices over a wide range of superhelix densities. We describe a very simple model of such a superhelix in which twisting and bending forces are in balance, subject both to topological constraints and to a limitation on the distance of closet approach of the interwound duplexes of the superhelix. The model is consistent with some of the observed physical properties of closed circular DNA, and suggests that there may be severe limits to the range of allowable geometries for the superhelix structure of minimum energy.", "contents": "A simple model of DNA superhelices in solution. Closed circular DNA molecules in aqueous solution take the form of interwound superhelices over a wide range of superhelix densities. We describe a very simple model of such a superhelix in which twisting and bending forces are in balance, subject both to topological constraints and to a limitation on the distance of closet approach of the interwound duplexes of the superhelix. The model is consistent with some of the observed physical properties of closed circular DNA, and suggests that there may be severe limits to the range of allowable geometries for the superhelix structure of minimum energy."}
{"id": "PMID:205867", "title": "Interaction of ligands with the opiate receptors of brain membranes: regulation by ions and nucleotides.", "content": "This study shows that nucleotides, as well as ions, regulate the opiate receptors of brain. GMP-P(NH)P and Na(+) reduce the amount of steady-state specific [(3)H]dihydromorphine binding and increase the rate of dissociation of the ligand from the opiate receptor. In contrast, Mn(2+) decreases the rate of ligand dissociation and antagonizes the ability of Na(+) to increase dissociation. The effects of GMP-P(NH)P on steady-state binding and dissociation are not reversed by washing. Only GTP, GDP, ITP, and IMP-P(NH)P, in addition to GMP-P(NH)P, increase the rate of dihydromorphine dissociation. The site of nucleotide action appears to have high affinity: <1 muM GMP-P(NH)P produces half-maximal increases in ligand dissociation. GMP-P(NH)P- and Na(+)-directed increases in dissociation have also been found for the opiate agonists [(3)H]etorphine, [(3)H]Leu-enkephalin, and [(3)H]Met-enkephalin and the opiate antagonist [(3)H]naltrexone. Mn(2+)-directed decreases in dissociation have been found for the agonist [(3)H]-etorphine and the antagonist [(3)H]naltrexone. Although the plasma membrane receptors for a number of other neuro-transmitters and hormones are also regulated by guanine nucleotides, the opiate receptors appear unique because only they show nucleotide regulation of both agonist and antagonist binding.", "contents": "Interaction of ligands with the opiate receptors of brain membranes: regulation by ions and nucleotides. This study shows that nucleotides, as well as ions, regulate the opiate receptors of brain. GMP-P(NH)P and Na(+) reduce the amount of steady-state specific [(3)H]dihydromorphine binding and increase the rate of dissociation of the ligand from the opiate receptor. In contrast, Mn(2+) decreases the rate of ligand dissociation and antagonizes the ability of Na(+) to increase dissociation. The effects of GMP-P(NH)P on steady-state binding and dissociation are not reversed by washing. Only GTP, GDP, ITP, and IMP-P(NH)P, in addition to GMP-P(NH)P, increase the rate of dihydromorphine dissociation. The site of nucleotide action appears to have high affinity: <1 muM GMP-P(NH)P produces half-maximal increases in ligand dissociation. GMP-P(NH)P- and Na(+)-directed increases in dissociation have also been found for the opiate agonists [(3)H]etorphine, [(3)H]Leu-enkephalin, and [(3)H]Met-enkephalin and the opiate antagonist [(3)H]naltrexone. Mn(2+)-directed decreases in dissociation have been found for the agonist [(3)H]-etorphine and the antagonist [(3)H]naltrexone. Although the plasma membrane receptors for a number of other neuro-transmitters and hormones are also regulated by guanine nucleotides, the opiate receptors appear unique because only they show nucleotide regulation of both agonist and antagonist binding."}
{"id": "PMID:205868", "title": "Enrichment of special Novikoff hepatoma and regenerating liver mRNA by hybridization to cDNA-cellulose.", "content": "Total polysomal poly(A)+ RNA of Novikoff hepatoma and of 18-hr regenerating rat liver were compared by analysis of their in vitro translational products on two-dimensional isofocusing/sodium dodecyl sulfate gels. This technique resolved the translated proteins sufficiently to permit detection of quantitative and some qualitative differences between the two mRNA populations. Excess cDNA from regenerating liver or Novikoff hepatoma, covalently linked to cellulose, was used to adsorb the complementary mRNA sequences from Novikoff hepatoma or regenerating liver. As shown by two-dimensional gel electrophoresis, the translated products of the bound mRNA fractions contained proteins common to both tissues. Novikoff hepatoma mRNA which did not bind to regenerating liver cDNA was enriched in sequences encoding for proteins 11/5.1, 15/6.8, 40/8.2, and 65/5.1 (shown as molecular weight/pI). These polypeptides were not detectable in the translational products of regenerating liver mRNA. Regenerating liver mRNA that was not bound to Novikoff hepatoma cDNA was enriched in sequences coding for proteins 12.5/4.9, 13.5/7.4, 17/8.2, 24/5.5, and 46/6.4; these proteins were not found in the translational pattern from Novikoff hepatoma. These results show that adsorption of mRNA to solid-phase cDNA provides a valuable technique for differentiating mRNA species in related tissues and for corresponding enrichment of these specific mRNAs.", "contents": "Enrichment of special Novikoff hepatoma and regenerating liver mRNA by hybridization to cDNA-cellulose. Total polysomal poly(A)+ RNA of Novikoff hepatoma and of 18-hr regenerating rat liver were compared by analysis of their in vitro translational products on two-dimensional isofocusing/sodium dodecyl sulfate gels. This technique resolved the translated proteins sufficiently to permit detection of quantitative and some qualitative differences between the two mRNA populations. Excess cDNA from regenerating liver or Novikoff hepatoma, covalently linked to cellulose, was used to adsorb the complementary mRNA sequences from Novikoff hepatoma or regenerating liver. As shown by two-dimensional gel electrophoresis, the translated products of the bound mRNA fractions contained proteins common to both tissues. Novikoff hepatoma mRNA which did not bind to regenerating liver cDNA was enriched in sequences encoding for proteins 11/5.1, 15/6.8, 40/8.2, and 65/5.1 (shown as molecular weight/pI). These polypeptides were not detectable in the translational products of regenerating liver mRNA. Regenerating liver mRNA that was not bound to Novikoff hepatoma cDNA was enriched in sequences coding for proteins 12.5/4.9, 13.5/7.4, 17/8.2, 24/5.5, and 46/6.4; these proteins were not found in the translational pattern from Novikoff hepatoma. These results show that adsorption of mRNA to solid-phase cDNA provides a valuable technique for differentiating mRNA species in related tissues and for corresponding enrichment of these specific mRNAs."}
{"id": "PMID:205869", "title": "Participation of spectrin in Sendai virus-induced fusion of human erythrocyte ghosts.", "content": "Fusion of washed human erythrocyte ghosts could be induced by the addition of Sendai virus after they were loaded with bovine serum albumin and resealed. Antispectrin antibody purified on a spectrin-Sepharose column and sequestered in the ghosts at 4-5 mg/ml together with the albumin was highly inhibitory for the virus-induced cell fusion, whereas Fab fragments prepared from the same antibody were without effect. The virus-induced aggregation of intramembrane particles of human erythrocytes was also inhibited by the same concentrations of the antispectrin antibody. The virus-induced agglutinations of the ghosts and release of bovine serum albumin from the ghosts (which might be caused by fusion of the viral envelope to the erythrocyte membrane) were not inhibited by the sequestered antibody. Therefore, the antibody seems to inhibit fusion at the last step--i.e., fusion between adjacent erythrocyte membranes. Similarities and differences of the mode of participation of spectrin in the virus-induced fusion and in other membrane-linked phenomena of human erythrocytes are discussed.", "contents": "Participation of spectrin in Sendai virus-induced fusion of human erythrocyte ghosts. Fusion of washed human erythrocyte ghosts could be induced by the addition of Sendai virus after they were loaded with bovine serum albumin and resealed. Antispectrin antibody purified on a spectrin-Sepharose column and sequestered in the ghosts at 4-5 mg/ml together with the albumin was highly inhibitory for the virus-induced cell fusion, whereas Fab fragments prepared from the same antibody were without effect. The virus-induced aggregation of intramembrane particles of human erythrocytes was also inhibited by the same concentrations of the antispectrin antibody. The virus-induced agglutinations of the ghosts and release of bovine serum albumin from the ghosts (which might be caused by fusion of the viral envelope to the erythrocyte membrane) were not inhibited by the sequestered antibody. Therefore, the antibody seems to inhibit fusion at the last step--i.e., fusion between adjacent erythrocyte membranes. Similarities and differences of the mode of participation of spectrin in the virus-induced fusion and in other membrane-linked phenomena of human erythrocytes are discussed."}
{"id": "PMID:205870", "title": "Regulation of adenylate cyclase activity mediated by muscarinic acetylcholine receptors.", "content": "Carbachol, an activator of muscarinic acetylcholine receptors of NG108-15 hybrid cells, inhibits adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] rapidly and reversibly and slowly evokes a 200-300% increase in adenylate cyclase activity over a period of 24-30 hr. Both the inhibition of adenylate cyclase and the gradual increase in enzyme activity are dependent on muscarinic acetylcholine receptors and the receptor activator. Withdrawal of carbachol results in a gradual return of adenylate cyclase activity to control levels over a period of 6 hr; the half-life for decay of enzyme activity is 1.6 hr. These results show that muscarinic acetylcholine receptors mediate both transient and long-lived effects on adenylate cyclase activity that resemble those of opiates.", "contents": "Regulation of adenylate cyclase activity mediated by muscarinic acetylcholine receptors. Carbachol, an activator of muscarinic acetylcholine receptors of NG108-15 hybrid cells, inhibits adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] rapidly and reversibly and slowly evokes a 200-300% increase in adenylate cyclase activity over a period of 24-30 hr. Both the inhibition of adenylate cyclase and the gradual increase in enzyme activity are dependent on muscarinic acetylcholine receptors and the receptor activator. Withdrawal of carbachol results in a gradual return of adenylate cyclase activity to control levels over a period of 6 hr; the half-life for decay of enzyme activity is 1.6 hr. These results show that muscarinic acetylcholine receptors mediate both transient and long-lived effects on adenylate cyclase activity that resemble those of opiates."}
{"id": "PMID:205871", "title": "Genetic regulation of galactokinase in Tetrahymena by cyclic AMP glucose, and epinephrine.", "content": "We have found evidence that transcription of the galactokinase (ATP:D-galactose 1-phosphotransferase; EC 2.7.1.6) gene is inhibited, in the animal-like protozoan Tetrahymena, by dibutyryl adenosine 3':5'-cyclic monophosphate, glucose, and epinephrine. The specific activities of galactokinase in Tetrahymena cells grown in defined media with galactose or glycerol as the principal carbon source are equivalent; the specific activity in glucose minimal medium is [unk] the value. Thus, while there seems to be no specific induction of the enzyme by the substrate, galactose, there is a strong \"repression\" by glucose. This repression by glucose is mimicked, in glycerol-grown cells, by the addition of millimolar amounts of dibutyryl adenosine 3':5'-cyclic monophosphate or phosphodiesterase inhibitors such as caffeine and theophylline. When glucose-grown cells are washed and resuspended in carbohydrate-free medium, the galactokinase specific activity increases by as much as 10-fold within 12 hr. This increase is blocked by dibutyryl adenosine 3':5'-cyclic monophosphate and by epinephrine (synthesized by Tetrahymena, and previously shown to activate a membrane-bound adenylate cyclase in extracts of this organism), as well as by inhibitors of mRNA synthesis, maturation, and translation. Our results suggest that glucose and epinephrine can regulate transcription of the galactokinase gene by modulation of cyclic nucleotide levels. The observation that the nonmetabolized sugars 2-deoxyglucose, 2-deoxygalactose, and alpha-methylglucoside are as effective as glucose suggests that the sugar itself, or an immediate metabolite such as the 1-phosphate derivative, may be the effector.", "contents": "Genetic regulation of galactokinase in Tetrahymena by cyclic AMP glucose, and epinephrine. We have found evidence that transcription of the galactokinase (ATP:D-galactose 1-phosphotransferase; EC 2.7.1.6) gene is inhibited, in the animal-like protozoan Tetrahymena, by dibutyryl adenosine 3':5'-cyclic monophosphate, glucose, and epinephrine. The specific activities of galactokinase in Tetrahymena cells grown in defined media with galactose or glycerol as the principal carbon source are equivalent; the specific activity in glucose minimal medium is [unk] the value. Thus, while there seems to be no specific induction of the enzyme by the substrate, galactose, there is a strong \"repression\" by glucose. This repression by glucose is mimicked, in glycerol-grown cells, by the addition of millimolar amounts of dibutyryl adenosine 3':5'-cyclic monophosphate or phosphodiesterase inhibitors such as caffeine and theophylline. When glucose-grown cells are washed and resuspended in carbohydrate-free medium, the galactokinase specific activity increases by as much as 10-fold within 12 hr. This increase is blocked by dibutyryl adenosine 3':5'-cyclic monophosphate and by epinephrine (synthesized by Tetrahymena, and previously shown to activate a membrane-bound adenylate cyclase in extracts of this organism), as well as by inhibitors of mRNA synthesis, maturation, and translation. Our results suggest that glucose and epinephrine can regulate transcription of the galactokinase gene by modulation of cyclic nucleotide levels. The observation that the nonmetabolized sugars 2-deoxyglucose, 2-deoxygalactose, and alpha-methylglucoside are as effective as glucose suggests that the sugar itself, or an immediate metabolite such as the 1-phosphate derivative, may be the effector."}
{"id": "PMID:205872", "title": "Proteases induce secretion of collagenase and plasminogen activator by fibroblasts.", "content": "We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2-24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or alpha-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16-48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10(6) cells per 24 hr) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continued presence of proteolytic activity or on subsequent cell adhesion, spreading, or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, alpha(1)-antitrypsin, bovine serum albumin, collagen, and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.", "contents": "Proteases induce secretion of collagenase and plasminogen activator by fibroblasts. We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2-24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or alpha-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16-48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10(6) cells per 24 hr) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continued presence of proteolytic activity or on subsequent cell adhesion, spreading, or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, alpha(1)-antitrypsin, bovine serum albumin, collagen, and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells."}
{"id": "PMID:205873", "title": "Establishment of clonal human placental cells synthesizing human choriogonadotropin.", "content": "Seven clonal human placental cell lines were established by transformation of human first-trimester placental cells with simian virus 40. These transformed cells synthesized native human choriogonadotropin (chorionic gonadotropin) (hCG) as well as the free alpha and beta subunits of hCG. The amount of native hCG synthesized by these cells was, however, lower than the amount of free beta subunit. (Both hCG and the beta subunit are detected by the radioimmunoassay for beta subunit, but only hCG is detected by the radioreceptor assay.) The alpha and beta subunits produced by these transformed placental cells were heterogeneous in size; the sizes of the predominant alpha and beta species, however, corresponded to those of urinary alpha and beta subunits, respectively. The seven cell lines transformed by simian virus 40 had chromosome numbers from the near diploid to the near tetraploid range. Fluorescent staining demonstrated the Y chromosome in all the transformants. Furthermore, B-type glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase; EC 1.1.1.49) was present in all seven lines. These characteristics ruled out possible HeLa contamination of the transformed lines. Regulation of the synthesis of alpha and beta subunits plus hCG in these transformed human placental cells differed from the regulation in choriocarcinoma cells.", "contents": "Establishment of clonal human placental cells synthesizing human choriogonadotropin. Seven clonal human placental cell lines were established by transformation of human first-trimester placental cells with simian virus 40. These transformed cells synthesized native human choriogonadotropin (chorionic gonadotropin) (hCG) as well as the free alpha and beta subunits of hCG. The amount of native hCG synthesized by these cells was, however, lower than the amount of free beta subunit. (Both hCG and the beta subunit are detected by the radioimmunoassay for beta subunit, but only hCG is detected by the radioreceptor assay.) The alpha and beta subunits produced by these transformed placental cells were heterogeneous in size; the sizes of the predominant alpha and beta species, however, corresponded to those of urinary alpha and beta subunits, respectively. The seven cell lines transformed by simian virus 40 had chromosome numbers from the near diploid to the near tetraploid range. Fluorescent staining demonstrated the Y chromosome in all the transformants. Furthermore, B-type glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase; EC 1.1.1.49) was present in all seven lines. These characteristics ruled out possible HeLa contamination of the transformed lines. Regulation of the synthesis of alpha and beta subunits plus hCG in these transformed human placental cells differed from the regulation in choriocarcinoma cells."}
{"id": "PMID:205874", "title": "Inhibition of cholesteryl ester formation in human fibroblasts by an analogue of 7-ketocholesterol and by progesterone.", "content": "The synthesis of cholesteryl esters in cultured human fibroblasts is catalyzed by a microsomal acyl-coenzyme A:cholesterol acyltransferase (EC 2.3.1.26). The acyltransferase activity is enhanced when fibroblasts take up cholesterol contained in plasma low density lipoprotein. In the current studies two steroids, SC-31769 (an analogue of 7-ketocholesterol) and progesterone, were shown to inhibit acyltransferase activity in cell-free extracts of human fibroblasts. When added to intact cells, these steroids inhibited the incorporation of [(14)C]oleate into cellular cholesteryl [(14)C]oleate and reduced the accumulation of cholesteryl esters in fibroblasts exposed to low density lipoprotein. The inhibition of cholesteryl ester formation in intact cells by SC-31769 and progesterone was readily reversible. Neither compound inhibited the incorporation of [(14)C]oleate into [(14)C]triglycerides or [(14)C]phospholipids. When incubated with fibroblast monolayers at a concentration of 1 mug/ml, SC-31769 suppressed the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating); EC 1.1.1.34], the rate-controlling enzyme in cholesterol synthesis. In contrast, progesterone had no effect on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity at concentrations as high as 25 mug/ml. The availability of two types of steroid compounds that inhibit the acyltransferase activity and cholesteryl ester synthesis in human fibroblasts should prove useful in further studies of the regulatory mechanisms responsible for cholesteryl ester accumulation in human cells under normal and pathologic conditions.", "contents": "Inhibition of cholesteryl ester formation in human fibroblasts by an analogue of 7-ketocholesterol and by progesterone. The synthesis of cholesteryl esters in cultured human fibroblasts is catalyzed by a microsomal acyl-coenzyme A:cholesterol acyltransferase (EC 2.3.1.26). The acyltransferase activity is enhanced when fibroblasts take up cholesterol contained in plasma low density lipoprotein. In the current studies two steroids, SC-31769 (an analogue of 7-ketocholesterol) and progesterone, were shown to inhibit acyltransferase activity in cell-free extracts of human fibroblasts. When added to intact cells, these steroids inhibited the incorporation of [(14)C]oleate into cellular cholesteryl [(14)C]oleate and reduced the accumulation of cholesteryl esters in fibroblasts exposed to low density lipoprotein. The inhibition of cholesteryl ester formation in intact cells by SC-31769 and progesterone was readily reversible. Neither compound inhibited the incorporation of [(14)C]oleate into [(14)C]triglycerides or [(14)C]phospholipids. When incubated with fibroblast monolayers at a concentration of 1 mug/ml, SC-31769 suppressed the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating); EC 1.1.1.34], the rate-controlling enzyme in cholesterol synthesis. In contrast, progesterone had no effect on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity at concentrations as high as 25 mug/ml. The availability of two types of steroid compounds that inhibit the acyltransferase activity and cholesteryl ester synthesis in human fibroblasts should prove useful in further studies of the regulatory mechanisms responsible for cholesteryl ester accumulation in human cells under normal and pathologic conditions."}
{"id": "PMID:205875", "title": "Chimeric mice derived from human-mouse hybrid cells.", "content": "Mouse teratocarcinoma cells from the OTT6050 ascites tumor were established in tissue culture and selected for 5-bromodeoxyuridine (BrdUrd) resistance. The embryonal carcinoma cells grew without a feeder layer, remained deficient for thymidine kinase (EC 2.7.1.75), and differentiated like the original tumor into various tissues after subcutaneous injection into 129 mice. We fused the BrdUrd-resistant mouse teratocarcinoma cells with HT1080-6TG human diploid fibrosarcoma cells deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and selected for hybrid cells in hypoxanthine/aminopterin/thymidine medium. The resulting hybrid cells segregated human chromosomes quickly and retained one to three human chromosomes including chromosome 17 that carries the human genes for thymidine kinase and galactokinase (EC 2.7.1.6). Single hybrid cells from five independent clones containing human chromosome 17 were injected into mouse blastocysts bearing several genetic markers that affect the coat color phenotype and strain-specific enzyme variants in order to detect tissue differentiation derived from the injected cells. After the injection of single hybrid cells into a total of 103 experimental blastocysts that had been surgically transferred to pseudopregnant foster mothers, 49 mice were born and 2 of them clearly revealed coat mosaicism. In 2 of 17 mice thus far analyzed, the injected hybrid cells proved to be capable of participating substantially in development of seven different organs. However, human gene products have not yet been detected unequivocally in those tissues and weak human-specific galactokinase activity could be recovered only from two mosaic tissues. Our results demonstrate that, after in vitro culture and selection, at least some of the human-mouse hybrid cells still retain their in vivo potential to differentiate and become functionally integrated in the living organism. It now seems feasible to cycle mouse teratocarcinoma cells carrying human genetic material through mice via blastocyst injection to study human gene expression during differentiation.", "contents": "Chimeric mice derived from human-mouse hybrid cells. Mouse teratocarcinoma cells from the OTT6050 ascites tumor were established in tissue culture and selected for 5-bromodeoxyuridine (BrdUrd) resistance. The embryonal carcinoma cells grew without a feeder layer, remained deficient for thymidine kinase (EC 2.7.1.75), and differentiated like the original tumor into various tissues after subcutaneous injection into 129 mice. We fused the BrdUrd-resistant mouse teratocarcinoma cells with HT1080-6TG human diploid fibrosarcoma cells deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) and selected for hybrid cells in hypoxanthine/aminopterin/thymidine medium. The resulting hybrid cells segregated human chromosomes quickly and retained one to three human chromosomes including chromosome 17 that carries the human genes for thymidine kinase and galactokinase (EC 2.7.1.6). Single hybrid cells from five independent clones containing human chromosome 17 were injected into mouse blastocysts bearing several genetic markers that affect the coat color phenotype and strain-specific enzyme variants in order to detect tissue differentiation derived from the injected cells. After the injection of single hybrid cells into a total of 103 experimental blastocysts that had been surgically transferred to pseudopregnant foster mothers, 49 mice were born and 2 of them clearly revealed coat mosaicism. In 2 of 17 mice thus far analyzed, the injected hybrid cells proved to be capable of participating substantially in development of seven different organs. However, human gene products have not yet been detected unequivocally in those tissues and weak human-specific galactokinase activity could be recovered only from two mosaic tissues. Our results demonstrate that, after in vitro culture and selection, at least some of the human-mouse hybrid cells still retain their in vivo potential to differentiate and become functionally integrated in the living organism. It now seems feasible to cycle mouse teratocarcinoma cells carrying human genetic material through mice via blastocyst injection to study human gene expression during differentiation."}
{"id": "PMID:205876", "title": "Purification of nuclear antigens in Novikoff hepatoma.", "content": "Nuclear antigen in Novikoff hepatoma chromatin was partially purified and characterized. As indicated by complement fixation assay, this antigen was present in chromatin of embryonic livers and several transplantable tumors. It was not detected in normal tissue chromatins of the same animals. For its immunological specificity this protein antigen (molecular weight 45,000-60,000) had to be complexed with DNA. Preliminary experiments indicate that specific nuclear protein antigens are also present in human tissues and spontaneous malignancies.", "contents": "Purification of nuclear antigens in Novikoff hepatoma. Nuclear antigen in Novikoff hepatoma chromatin was partially purified and characterized. As indicated by complement fixation assay, this antigen was present in chromatin of embryonic livers and several transplantable tumors. It was not detected in normal tissue chromatins of the same animals. For its immunological specificity this protein antigen (molecular weight 45,000-60,000) had to be complexed with DNA. Preliminary experiments indicate that specific nuclear protein antigens are also present in human tissues and spontaneous malignancies."}
{"id": "PMID:205877", "title": "Transforming activity of Epstein-Barr virus obtained by superinfection of Raji cells.", "content": "Epstein-Barr virus obtained by superinfection of Raji cells with Epstein-Barr virus recovered from P3HR1 cells (HRI virus) transformed human lymphocytes, but it did not superinfect Raji cells. A human lymphoblastoid cell line, HLB, established by such transformation contained 22 Epstein-Barr virus genomes per cell and Epstein-Barr virus-associated nuclear antigen, and a few cells contained early or viral capsid antigen complexes. Chromosomal analysis revealed that HLB-cells were diploid with normal female karyotypes. Replication of Epstein-Barr virus DNA and inhibition of host cell DNA synthesis were observed in HLB cells after superinfection with HR1 virus.", "contents": "Transforming activity of Epstein-Barr virus obtained by superinfection of Raji cells. Epstein-Barr virus obtained by superinfection of Raji cells with Epstein-Barr virus recovered from P3HR1 cells (HRI virus) transformed human lymphocytes, but it did not superinfect Raji cells. A human lymphoblastoid cell line, HLB, established by such transformation contained 22 Epstein-Barr virus genomes per cell and Epstein-Barr virus-associated nuclear antigen, and a few cells contained early or viral capsid antigen complexes. Chromosomal analysis revealed that HLB-cells were diploid with normal female karyotypes. Replication of Epstein-Barr virus DNA and inhibition of host cell DNA synthesis were observed in HLB cells after superinfection with HR1 virus."}
{"id": "PMID:205878", "title": "Differences in behavior and prognosis between leukemic and lymphomatous forms of a transplantable hamster lymphocytic neoplasm induced by simian virus 40.", "content": "A lymphocytic leukemia of probable monoclonal derivation, induced in a Syrian golden hamster by the oncogenic DNA simian virus 40, was adapted to grow in the allogeneic host either as leukemia or as lymphoma. The leukemia, which was produced by transplanting subcutaneously neoplastic lymphocytes that had circulated through and/or proliferated in lymph nodes and spleen, was characterized by dissemination with systemic manifestations and poor prognosis. The lymphoma, which was produced by transplanting subcutaneously neoplastic lymphocytes that had proliferated at subcutaneous sites of cell implantation, was characterized by localization and favorable prognosis. Evidence indicates that the tissue environment the neoplastic lymphocytes encounter during circulation and/or proliferation regulates their subsequent behavior in the intact host. Since the leukemic and lymphomatous forms of this animal model resemble very closely the analogous human lymphocytic neoplasms, it can serve as a means to elucidate the factors responsible for the differences in their behavior and to determine how these differences may influence prognosis and response to therapy.", "contents": "Differences in behavior and prognosis between leukemic and lymphomatous forms of a transplantable hamster lymphocytic neoplasm induced by simian virus 40. A lymphocytic leukemia of probable monoclonal derivation, induced in a Syrian golden hamster by the oncogenic DNA simian virus 40, was adapted to grow in the allogeneic host either as leukemia or as lymphoma. The leukemia, which was produced by transplanting subcutaneously neoplastic lymphocytes that had circulated through and/or proliferated in lymph nodes and spleen, was characterized by dissemination with systemic manifestations and poor prognosis. The lymphoma, which was produced by transplanting subcutaneously neoplastic lymphocytes that had proliferated at subcutaneous sites of cell implantation, was characterized by localization and favorable prognosis. Evidence indicates that the tissue environment the neoplastic lymphocytes encounter during circulation and/or proliferation regulates their subsequent behavior in the intact host. Since the leukemic and lymphomatous forms of this animal model resemble very closely the analogous human lymphocytic neoplasms, it can serve as a means to elucidate the factors responsible for the differences in their behavior and to determine how these differences may influence prognosis and response to therapy."}
{"id": "PMID:205879", "title": "Protein kinase activity associated with the avian sarcoma virus src gene product.", "content": "Incorporation of phosphorus from [gamma-32P]ATP into protein was catalyzed by specific immunoprecipitates from avian sarcoma virus (ASV)-transformed avian and mammalian cells. This incorporation was observed only when antiserum from tumor-bearing rabbits able to specifically precipitate the ASV sarcoma gene product, p60src, was used to immunoprecipitate antigens from transformed cell lysates. Immunoprecipitates of extracts from normal cells or cells infected with a transformation-defective ASV mutant showed no activity in this assay, nor did any immune complexes formed with normal rabbit serum and any of the cell extracts tested. The expression of the protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) was growth temperature-dependent in cells infected with an ASV mutant temperature-sensitive for the transformation. These results on an enzymatic activity associated with the ASV transforming protein are discussed in terms of protein phosphorylation as a mechanism for viral transformation.", "contents": "Protein kinase activity associated with the avian sarcoma virus src gene product. Incorporation of phosphorus from [gamma-32P]ATP into protein was catalyzed by specific immunoprecipitates from avian sarcoma virus (ASV)-transformed avian and mammalian cells. This incorporation was observed only when antiserum from tumor-bearing rabbits able to specifically precipitate the ASV sarcoma gene product, p60src, was used to immunoprecipitate antigens from transformed cell lysates. Immunoprecipitates of extracts from normal cells or cells infected with a transformation-defective ASV mutant showed no activity in this assay, nor did any immune complexes formed with normal rabbit serum and any of the cell extracts tested. The expression of the protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) was growth temperature-dependent in cells infected with an ASV mutant temperature-sensitive for the transformation. These results on an enzymatic activity associated with the ASV transforming protein are discussed in terms of protein phosphorylation as a mechanism for viral transformation."}
{"id": "PMID:205880", "title": "Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus.", "content": "Estradiol-17beta administration to young (10- to 12-week-old) rabbits to produce the \"estrogen-dominated\" uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In \"progesterone-dominated\" uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatment, the contractile response to oxytocin in vitro was selectively abolished; the response to methacholine was unaffected. Parallel changes were observed in the concentration (but not affinity) of specific sites in uterine microsomal membranes that bind [(3)H]oxytocin with selectivity features expected for oxytocin receptors. Thus, estrogen-dominated uteri have an increased number of specific [(3)H]oxytocin binding sites per mg of membrane protein relative to untreated controls, whereas specific oxytocin binding sites are reduced to barely detectable levels in the progesterone-dominated uterus. Similar results are obtained when binding sites are measured in membranes from the myometrium of estrogen- or progesterone-dominated uteri. Short-term (24-hr) progesterone administration to estrogen-pretreated rabbits decreased, but did not abolish, specific [(3)H]oxytocin binding; the concentration of specific [(3)H]oxytocin binding sites was reduced without influence on the affinity of these sites. A sublethal dose of actinomycin D, administered over a 24-hr period to rabbits pretreated with estradiol for 4 days, likewise reduced specific oxytocin binding; additive effects were not observed when progesterone and actinomycin D were administered together. These results suggest that the regulatory effects of estrogens and progesterone upon the rabbit uterine contractile response to oxytocin are achieved, at least in part, by the opposing actions of these steroids in regulating the number of oxytocin receptors in smooth muscle cells. Estradiol increased the concentration of uterine oxytocin receptors; the maintenance of high receptor levels appears to depend upon the continuous de novo synthesis of oxytocin receptors. In contrast, progesterone, like actinomycin D, appears to act at the nuclear locus to repress synthesis of oxytocin receptors.", "contents": "Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus. Estradiol-17beta administration to young (10- to 12-week-old) rabbits to produce the \"estrogen-dominated\" uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In \"progesterone-dominated\" uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatment, the contractile response to oxytocin in vitro was selectively abolished; the response to methacholine was unaffected. Parallel changes were observed in the concentration (but not affinity) of specific sites in uterine microsomal membranes that bind [(3)H]oxytocin with selectivity features expected for oxytocin receptors. Thus, estrogen-dominated uteri have an increased number of specific [(3)H]oxytocin binding sites per mg of membrane protein relative to untreated controls, whereas specific oxytocin binding sites are reduced to barely detectable levels in the progesterone-dominated uterus. Similar results are obtained when binding sites are measured in membranes from the myometrium of estrogen- or progesterone-dominated uteri. Short-term (24-hr) progesterone administration to estrogen-pretreated rabbits decreased, but did not abolish, specific [(3)H]oxytocin binding; the concentration of specific [(3)H]oxytocin binding sites was reduced without influence on the affinity of these sites. A sublethal dose of actinomycin D, administered over a 24-hr period to rabbits pretreated with estradiol for 4 days, likewise reduced specific oxytocin binding; additive effects were not observed when progesterone and actinomycin D were administered together. These results suggest that the regulatory effects of estrogens and progesterone upon the rabbit uterine contractile response to oxytocin are achieved, at least in part, by the opposing actions of these steroids in regulating the number of oxytocin receptors in smooth muscle cells. Estradiol increased the concentration of uterine oxytocin receptors; the maintenance of high receptor levels appears to depend upon the continuous de novo synthesis of oxytocin receptors. In contrast, progesterone, like actinomycin D, appears to act at the nuclear locus to repress synthesis of oxytocin receptors."}
{"id": "PMID:205883", "title": "Morphological and biological features of MC-29 virus-induced liver tumors in chicken.", "content": "Further comparative studies on the biological and biochemical features of virus-derived transplantable and chemically induced hepatomas may contribute to the knowledge of human hepatomas. Evidence for the reprogramming of gene expression found in chemically induced transplantable hepatomas [22] was also found in this virus-derived hepatoma.", "contents": "Morphological and biological features of MC-29 virus-induced liver tumors in chicken. Further comparative studies on the biological and biochemical features of virus-derived transplantable and chemically induced hepatomas may contribute to the knowledge of human hepatomas. Evidence for the reprogramming of gene expression found in chemically induced transplantable hepatomas [22] was also found in this virus-derived hepatoma."}
{"id": "PMID:205886", "title": "Hydrochloric acid and cyclic 3'.5'-adenosine monophosphate content of rodent gastric juice after halothane administration.", "content": "Pulmonary aspiration of gastric contents during general anesthesia has always been a serious problem. Morbidity and mortality depend on the volume and acidity of the aspirated material. The anesthetic agent itself might affect gastric acid secretion. The effect of halothane (5, 10 and 20 mg/kg intravenously) on HCl secretion and cAMP content of gastric juice in pyloric and cardiac ligated male Sprague-Dawley rats was investigated. Compared with the control group, halothane significantly increased both HCl secretion and cAMP content of gastric juice, but to a lesser degree at the higher doses (p less than 0.05).", "contents": "Hydrochloric acid and cyclic 3'.5'-adenosine monophosphate content of rodent gastric juice after halothane administration. Pulmonary aspiration of gastric contents during general anesthesia has always been a serious problem. Morbidity and mortality depend on the volume and acidity of the aspirated material. The anesthetic agent itself might affect gastric acid secretion. The effect of halothane (5, 10 and 20 mg/kg intravenously) on HCl secretion and cAMP content of gastric juice in pyloric and cardiac ligated male Sprague-Dawley rats was investigated. Compared with the control group, halothane significantly increased both HCl secretion and cAMP content of gastric juice, but to a lesser degree at the higher doses (p less than 0.05)."}
{"id": "PMID:205887", "title": "Effects of opiates on cAMP in homogenates and slices of rat striata.", "content": "In slices of rat striata, incubated in a depolarizing medium (53 mM K+), morphine decreased by concentration of cAMP even in concentrations as low as 0.5 micron. This effect was inhibited by naloxone. Levorphanol, but not dextrorphan, induced a similar effect as morphine. In tissue, homogenized in a hypotonic medium, morphine (5-50 micron) also slightly decreased the concentration of cAMP, which was antagonized by naloxone. Neigher slices nor homogenates of morphine-withdrawn rats showed any alteration in the concentration of cAMP.", "contents": "Effects of opiates on cAMP in homogenates and slices of rat striata. In slices of rat striata, incubated in a depolarizing medium (53 mM K+), morphine decreased by concentration of cAMP even in concentrations as low as 0.5 micron. This effect was inhibited by naloxone. Levorphanol, but not dextrorphan, induced a similar effect as morphine. In tissue, homogenized in a hypotonic medium, morphine (5-50 micron) also slightly decreased the concentration of cAMP, which was antagonized by naloxone. Neigher slices nor homogenates of morphine-withdrawn rats showed any alteration in the concentration of cAMP."}
{"id": "PMID:205888", "title": "General pharmacology of ergot alkaloids.", "content": "Ergot alkaloids possess a wide and divergent spectrum of central and peripheral pharmacodynamic actions. They interfere with different receptor sites to stimulate and/or inhibit effector structures. The concept of partial agonism on alpha-adrenoreceptors has replaced the ancient hypothesis of direct stimulation of vascular and uterine smooth muscle. The mechanisms which are considered to be relevant for the therapeutic use of dihydroergotamine, a potent drug increasing venous tone, and of bromocriptine, a specific inhibitor of prolactin secretion, are discussed in more detail.", "contents": "General pharmacology of ergot alkaloids. Ergot alkaloids possess a wide and divergent spectrum of central and peripheral pharmacodynamic actions. They interfere with different receptor sites to stimulate and/or inhibit effector structures. The concept of partial agonism on alpha-adrenoreceptors has replaced the ancient hypothesis of direct stimulation of vascular and uterine smooth muscle. The mechanisms which are considered to be relevant for the therapeutic use of dihydroergotamine, a potent drug increasing venous tone, and of bromocriptine, a specific inhibitor of prolactin secretion, are discussed in more detail."}
{"id": "PMID:205889", "title": "Ergot alkaloids and cyclic nucleotides in the CNS.", "content": "Ergotamine and dihydroergotamine show a higher blocking effect towards the dopamine-induced stimulation of adenylate cyclase activity than to the apomorphine-induced stimulation. This could reflect a possible specificity of the compound to dopaminergic receptor. Bromocriptine blocks in a more competitive way the activation of adenylate cyclase induced in vitro by dopamine, but increases the levels of cAMP in rat striatum in vivo. This effect is blocked by haloperidol and reserpine when given together with bromocriptine. On the base of the biochemical observation and various behavioral data the drug has been used in the treatment of parkinsonism with contrasting results and of Huntington's chorea. Moreover, bromocriptine induces a marked decrease of cGMP levels in cerebellum such as haloperidol and chloropromazine while apomorphine and other dopaminergic drugs increase the levels of cGMP. At the dose of 1 mg/kg, bromocriptine as well as DH-ergotoxine markedly reduces the levels of striatal DOPAC.", "contents": "Ergot alkaloids and cyclic nucleotides in the CNS. Ergotamine and dihydroergotamine show a higher blocking effect towards the dopamine-induced stimulation of adenylate cyclase activity than to the apomorphine-induced stimulation. This could reflect a possible specificity of the compound to dopaminergic receptor. Bromocriptine blocks in a more competitive way the activation of adenylate cyclase induced in vitro by dopamine, but increases the levels of cAMP in rat striatum in vivo. This effect is blocked by haloperidol and reserpine when given together with bromocriptine. On the base of the biochemical observation and various behavioral data the drug has been used in the treatment of parkinsonism with contrasting results and of Huntington's chorea. Moreover, bromocriptine induces a marked decrease of cGMP levels in cerebellum such as haloperidol and chloropromazine while apomorphine and other dopaminergic drugs increase the levels of cGMP. At the dose of 1 mg/kg, bromocriptine as well as DH-ergotoxine markedly reduces the levels of striatal DOPAC."}
{"id": "PMID:205891", "title": "Pituitary hormones and ergot alkaloids.", "content": "From the data presented it appears that ergot drugs are both a useful tool for use in the study of neuroendocrine control of pituitary hormone secretion and a valid pharmacologic weapon for treatment of hyperprolactinemic states, GH and, probably, ACTH and MSH hypersecretion. In fact, they are capable of a long-lasting disruption of PRL secretion from a normal or tumoral pituitary gland, are unable to affect directly the somatotrophs of an intact AP, but inhibit GH and, possibly, ACTH secretion from a hyperplastic or tumoral gland. Ergolines also exert clear-cut PRL-lowering effects and are capable of suppressing GH secretion in acromegaly. The intimate mechanism(s) and hence site(s) of action of some of these compounds await clarification.", "contents": "Pituitary hormones and ergot alkaloids. From the data presented it appears that ergot drugs are both a useful tool for use in the study of neuroendocrine control of pituitary hormone secretion and a valid pharmacologic weapon for treatment of hyperprolactinemic states, GH and, probably, ACTH and MSH hypersecretion. In fact, they are capable of a long-lasting disruption of PRL secretion from a normal or tumoral pituitary gland, are unable to affect directly the somatotrophs of an intact AP, but inhibit GH and, possibly, ACTH secretion from a hyperplastic or tumoral gland. Ergolines also exert clear-cut PRL-lowering effects and are capable of suppressing GH secretion in acromegaly. The intimate mechanism(s) and hence site(s) of action of some of these compounds await clarification."}
{"id": "PMID:205893", "title": "The role of the corpus callosum in the interhemispheric transmission of epileptic electrical activity.", "content": "In acute experiments on 49 curarized adult rats without general anaesthesia, we studied the transmission of discharges of cortical penicillin foci between the two hemispheres after transecting the corpus callosum. Projected discharges of the cortical penicillin focus appeared in the contralateral hemisphere later than in the controls and had a very different shape. The interhemispheric response of the experimental rats consisted of a small positive and a small negative deflection with long latent periods. Focal discharges could be triggered by electrical stimulat;on of the contralateral hemisphere only irregularly and for short periods of time. In rats with a transected corpus callosum, two symmetrical cortical foci at first behaved independently of each other; their synchronization then slowly improved, but never attained 100 per cent. The corpus callosum is the preferential pathway for interhemispheric transmission of focal activity. Transection of this pathway makes the transmission conditions much worse, but further connections, with a longer conduction time and lower efficacy, gradually come into action.", "contents": "The role of the corpus callosum in the interhemispheric transmission of epileptic electrical activity. In acute experiments on 49 curarized adult rats without general anaesthesia, we studied the transmission of discharges of cortical penicillin foci between the two hemispheres after transecting the corpus callosum. Projected discharges of the cortical penicillin focus appeared in the contralateral hemisphere later than in the controls and had a very different shape. The interhemispheric response of the experimental rats consisted of a small positive and a small negative deflection with long latent periods. Focal discharges could be triggered by electrical stimulat;on of the contralateral hemisphere only irregularly and for short periods of time. In rats with a transected corpus callosum, two symmetrical cortical foci at first behaved independently of each other; their synchronization then slowly improved, but never attained 100 per cent. The corpus callosum is the preferential pathway for interhemispheric transmission of focal activity. Transection of this pathway makes the transmission conditions much worse, but further connections, with a longer conduction time and lower efficacy, gradually come into action."}
{"id": "PMID:205897", "title": "[Granular cell myoblastoma of the mammary gland and its differentiation from mammary carcinoma (author's transl)].", "content": "Report of a case with granular cell tumor of the mammary gland. These tumors are observed infrequently and are important because of the difficulty to differentiate those lesions from carcinoma of the breast. The accurate diagnosis is possible by cytology and microscopy.", "contents": "[Granular cell myoblastoma of the mammary gland and its differentiation from mammary carcinoma (author's transl)]. Report of a case with granular cell tumor of the mammary gland. These tumors are observed infrequently and are important because of the difficulty to differentiate those lesions from carcinoma of the breast. The accurate diagnosis is possible by cytology and microscopy."}
{"id": "PMID:205898", "title": "The pleural tail sign.", "content": "The pleural tail sign is widely thought to indicate malignancy. However, of 18 patients with the tail sign, 9 had benign disease. Bronchioloalveolar carcinoma was the most common malignant tumor, but adenocarcinoma, squamous-cell carcinoma, and metastatic adenocarcinoma of the colon were also found. The location of nodules and the radiographic characteristics of the pleural tails did not help differentiate benign from malignant lesions. However, nodules 2 cm or larger were malignant while those 1 cm or smaller were benign. Histologically, pleural tails reflected thickened, fibrotic connective tissue septae with indrawing of the visceral pleura. Their occurrence with neoplasm reflects desmoplastic reaction or scar carcinoma.", "contents": "The pleural tail sign. The pleural tail sign is widely thought to indicate malignancy. However, of 18 patients with the tail sign, 9 had benign disease. Bronchioloalveolar carcinoma was the most common malignant tumor, but adenocarcinoma, squamous-cell carcinoma, and metastatic adenocarcinoma of the colon were also found. The location of nodules and the radiographic characteristics of the pleural tails did not help differentiate benign from malignant lesions. However, nodules 2 cm or larger were malignant while those 1 cm or smaller were benign. Histologically, pleural tails reflected thickened, fibrotic connective tissue septae with indrawing of the visceral pleura. Their occurrence with neoplasm reflects desmoplastic reaction or scar carcinoma."}
{"id": "PMID:205899", "title": "The evaluation of ependymal and subependymal lesions by cranial computed tomography.", "content": "Lesions of the ventricular ependyma and its derivatives can be visualized by CT scans, and their nature and extent can be determined. Generalized enhancement of the ependyma following the administration of intravenous contrast media can be seen with spendymoma, medulloblastoma, metastatic dysgerminoma, glioblastoma multiforme, and ependymitis. Localized ependymal enhancement can often be identified in the presence of acute ventriculitis, vascular anomalies or malformations, cerebral infarctions with luxury perfusion, and vascular neoplasms.", "contents": "The evaluation of ependymal and subependymal lesions by cranial computed tomography. Lesions of the ventricular ependyma and its derivatives can be visualized by CT scans, and their nature and extent can be determined. Generalized enhancement of the ependyma following the administration of intravenous contrast media can be seen with spendymoma, medulloblastoma, metastatic dysgerminoma, glioblastoma multiforme, and ependymitis. Localized ependymal enhancement can often be identified in the presence of acute ventriculitis, vascular anomalies or malformations, cerebral infarctions with luxury perfusion, and vascular neoplasms."}
{"id": "PMID:205900", "title": "Pitfalls in the radiographic diagnosis of angiofibroma.", "content": "Radiographic findings previously thought pathognomonic for juvenile nasopharyngeal angiofibroma are anterior bowing of the posterior wall of the maxillary antrum on plain films or tomography, and a dense homogeneous blush on angiography. Two patients presented with nasopharyngeal masses which mimicked angiofibroma radiographically: one mass was a lymphoepithelioma and the other was a fibrous tumor. Constitutional symptoms and atypical physical findings should alert the physician to a diagnosis other than juvenile nasopharyngeal angiofibroma.", "contents": "Pitfalls in the radiographic diagnosis of angiofibroma. Radiographic findings previously thought pathognomonic for juvenile nasopharyngeal angiofibroma are anterior bowing of the posterior wall of the maxillary antrum on plain films or tomography, and a dense homogeneous blush on angiography. Two patients presented with nasopharyngeal masses which mimicked angiofibroma radiographically: one mass was a lymphoepithelioma and the other was a fibrous tumor. Constitutional symptoms and atypical physical findings should alert the physician to a diagnosis other than juvenile nasopharyngeal angiofibroma."}
{"id": "PMID:205901", "title": "99mTc-pyrophosphate bone imaging in osteopoikilosis, osteopathia striata, and melorheostosis.", "content": "Technetium-99m pyrophosphate bone images were contrasted with radiographic findings in two patients with osteopoikilosis, one with osteopathia striata, and one with melorheostosis. Despite the striking radiographic findings, scans were normal in osteopoikilosis and osteopathia striata. In melorheostosis, focal increased radiopharmaceutical accumulation appeared in each radiographically abnormal area. Technetium-99m pyrophosphate bone images should prove helpful when superimposed osseous disease must be differentiated from osteopoikilosis, osteopathia striata, or melorheostosis.", "contents": "99mTc-pyrophosphate bone imaging in osteopoikilosis, osteopathia striata, and melorheostosis. Technetium-99m pyrophosphate bone images were contrasted with radiographic findings in two patients with osteopoikilosis, one with osteopathia striata, and one with melorheostosis. Despite the striking radiographic findings, scans were normal in osteopoikilosis and osteopathia striata. In melorheostosis, focal increased radiopharmaceutical accumulation appeared in each radiographically abnormal area. Technetium-99m pyrophosphate bone images should prove helpful when superimposed osseous disease must be differentiated from osteopoikilosis, osteopathia striata, or melorheostosis."}
{"id": "PMID:205902", "title": "Juvenile nasopharyngeal angiofibroma. A report of seven cases.", "content": "Seven cases of biopsy-proved juvenile nasopharyngeal angiofibroma are presented. All patients were males. Examination under anesthesia and tomography and angiography were very rewarding in determining the full extent of tumor. Selective carotid angiography revealed a characteristic early arterial phase with reticulated vessels, and a homogeneous blush continuing into the venous phase without early draining veins. The tumor has a strong predilection for young males. Chromosomal studies and estimation of 17-ketosteroids in 4 patients were normal. None of the patients demonstrated sexual underdevelopment. All were treated by external radiotherapy with 3000 rads in 15 fractions in three weeks with good results. There were no undue side effects.", "contents": "Juvenile nasopharyngeal angiofibroma. A report of seven cases. Seven cases of biopsy-proved juvenile nasopharyngeal angiofibroma are presented. All patients were males. Examination under anesthesia and tomography and angiography were very rewarding in determining the full extent of tumor. Selective carotid angiography revealed a characteristic early arterial phase with reticulated vessels, and a homogeneous blush continuing into the venous phase without early draining veins. The tumor has a strong predilection for young males. Chromosomal studies and estimation of 17-ketosteroids in 4 patients were normal. None of the patients demonstrated sexual underdevelopment. All were treated by external radiotherapy with 3000 rads in 15 fractions in three weeks with good results. There were no undue side effects."}
{"id": "PMID:205926", "title": "The effect of dihydroxy-2-aminotetraline (DATs) on dopamine and beta type adenylate cyclases.", "content": "A number of DATS have been studied for agonist activity with dopamine (DA) and beta (beta) type adenylate cyclases and the most potent ones were found among the 6,7-DATs and the 5,6-DATs, respectively. None of the compounds tested possessed antagonist activity. The observed activities were not expected on the basis of structural analysis of model compounds such as apomorphine and 6,7-dihydroxy-1-benzyltetrahydroisoquinoline. A new view was constructed which suggests that the nitrogens of the DAT compounds were positioned better than those of the model compounds with regard to their binding sites.", "contents": "The effect of dihydroxy-2-aminotetraline (DATs) on dopamine and beta type adenylate cyclases. A number of DATS have been studied for agonist activity with dopamine (DA) and beta (beta) type adenylate cyclases and the most potent ones were found among the 6,7-DATs and the 5,6-DATs, respectively. None of the compounds tested possessed antagonist activity. The observed activities were not expected on the basis of structural analysis of model compounds such as apomorphine and 6,7-dihydroxy-1-benzyltetrahydroisoquinoline. A new view was constructed which suggests that the nitrogens of the DAT compounds were positioned better than those of the model compounds with regard to their binding sites."}
{"id": "PMID:205927", "title": "Effect of endotoxin on uterine cycle AMP in pregnant mice.", "content": "The effect of endotoxin (LPS) on uterine cAMP was determined by measuring the levels of cAMP and cAMP phosphodiesterase after challenge. Two LPS preparations, isolated from wild type (WT) and Re chemotype mutant cells of Salmonella typhimurium were used. The pattern of termination differed with WT LPS resulting in expulsion of the fetuses, and Re LPS primarily causing the resorption of the fetuses. The animals challenged with WT LPS showed a decrease in uterine cAMP when the mice were starting to expel the fetuses while the Re LPS treated group maintained control levels of cAMP. Cyclic AMP phosphodiesterase also decreased in WT LPS and not the Re LPS group. These results suggest the possibility that uterine cAMP is involved in the expulsion of the fetuses.", "contents": "Effect of endotoxin on uterine cycle AMP in pregnant mice. The effect of endotoxin (LPS) on uterine cAMP was determined by measuring the levels of cAMP and cAMP phosphodiesterase after challenge. Two LPS preparations, isolated from wild type (WT) and Re chemotype mutant cells of Salmonella typhimurium were used. The pattern of termination differed with WT LPS resulting in expulsion of the fetuses, and Re LPS primarily causing the resorption of the fetuses. The animals challenged with WT LPS showed a decrease in uterine cAMP when the mice were starting to expel the fetuses while the Re LPS treated group maintained control levels of cAMP. Cyclic AMP phosphodiesterase also decreased in WT LPS and not the Re LPS group. These results suggest the possibility that uterine cAMP is involved in the expulsion of the fetuses."}
{"id": "PMID:205928", "title": "alpha and beta-adrenoceptors in chicken airways.", "content": "Isolated chicken bronchus (which had been partially contracted to carbachol) relaxes to isoproterenol and epinephrine but contracts weakly to phenylephrine. Propranolol (a beta-adrenoceptor blocker) antagonizes isoproterenol and reverses epinephrine-induced relaxations to feeble contractions. Phenylephrine-induced bronchoconstrictions and constrictions to epinephrine (in the presence of beta-blockade) were blocked by phentolamine. The results of this study showed the predominance of beta-)inhibitory) adrenoceptors and some alpha-(excitatory) adrenoceptors in the bronchus of the adult domestic fowl.", "contents": "alpha and beta-adrenoceptors in chicken airways. Isolated chicken bronchus (which had been partially contracted to carbachol) relaxes to isoproterenol and epinephrine but contracts weakly to phenylephrine. Propranolol (a beta-adrenoceptor blocker) antagonizes isoproterenol and reverses epinephrine-induced relaxations to feeble contractions. Phenylephrine-induced bronchoconstrictions and constrictions to epinephrine (in the presence of beta-blockade) were blocked by phentolamine. The results of this study showed the predominance of beta-)inhibitory) adrenoceptors and some alpha-(excitatory) adrenoceptors in the bronchus of the adult domestic fowl."}
{"id": "PMID:205929", "title": "Glomerulonephritis in malignant extra-renal neoplasms. Experimental study on mice using the method of immunofluorescence.", "content": "Histologic and immunofluorescence studies were done in the murine kidneys (strain C3HAvy) suffering a spontaneous cancer of the liver. Proliferative glomerulonephritis has been found in 17 animals and memranproliferative glomerulonephritis with \"wire loop\" appearance in 6 animals. The glomeruli of all animals presented immune complex deposition in the mesangium and along the glomerular basement membrane. Furthermore, heavy intensity of IgG complex deposition was observed in animals with membranproliferative glomerulonephritis. The latter animals had developed a poorly differentiated liver cancer.", "contents": "Glomerulonephritis in malignant extra-renal neoplasms. Experimental study on mice using the method of immunofluorescence. Histologic and immunofluorescence studies were done in the murine kidneys (strain C3HAvy) suffering a spontaneous cancer of the liver. Proliferative glomerulonephritis has been found in 17 animals and memranproliferative glomerulonephritis with \"wire loop\" appearance in 6 animals. The glomeruli of all animals presented immune complex deposition in the mesangium and along the glomerular basement membrane. Furthermore, heavy intensity of IgG complex deposition was observed in animals with membranproliferative glomerulonephritis. The latter animals had developed a poorly differentiated liver cancer."}
{"id": "PMID:205924", "title": "[The Hoffmann reflex in the normal new-borns. Post-natal evolution of the conduction velocity of the alpha motor and the Ia sensitive fibres of the ulnar nerve (author's transl)].", "content": "The conduction velocities of the alpha motor fibres and the IA sensitive fibres of the ulnar nerve have been studied in a group of full term newborn babies and during the neonatal period. At birth the average conduction velocity of the alpha motor fibres is 25,7 m/sec (sigma = to 2,4 m/sec) that of the IA afferent fibres is 35 m/sec (sigma = to 3,2 m/sec). The post natal evolution of the conduction velocity as a function of age has been established for both types of fibres. The time required for nervous conduction between the olecranon process and the wrist diminishes clearly in the course of the first two years because of a discordance between the augmentations of the length and of the diameter of the nerve fibers. The evolution of this conduction time as a function of the age and of the length of the forearm, has been established for the period between birth and the age of six years. The Hoffmann reflex in the inferior limb is present in all infants at birth; its latency is 14,2 msec; the ratio R = to Hmax/Mmax x 100 = to 55,75 p. 100 is identical to that found in the adult. A Hoffmann reflex exists in 66 p. 100 of the population studied in the ulnar nerve. Its latency is 11,1 msec; R = to Hmax/Mmax is equal to 30 p. 100. This reflex disappears progressively during the development.", "contents": "[The Hoffmann reflex in the normal new-borns. Post-natal evolution of the conduction velocity of the alpha motor and the Ia sensitive fibres of the ulnar nerve (author's transl)]. The conduction velocities of the alpha motor fibres and the IA sensitive fibres of the ulnar nerve have been studied in a group of full term newborn babies and during the neonatal period. At birth the average conduction velocity of the alpha motor fibres is 25,7 m/sec (sigma = to 2,4 m/sec) that of the IA afferent fibres is 35 m/sec (sigma = to 3,2 m/sec). The post natal evolution of the conduction velocity as a function of age has been established for both types of fibres. The time required for nervous conduction between the olecranon process and the wrist diminishes clearly in the course of the first two years because of a discordance between the augmentations of the length and of the diameter of the nerve fibers. The evolution of this conduction time as a function of the age and of the length of the forearm, has been established for the period between birth and the age of six years. The Hoffmann reflex in the inferior limb is present in all infants at birth; its latency is 14,2 msec; the ratio R = to Hmax/Mmax x 100 = to 55,75 p. 100 is identical to that found in the adult. A Hoffmann reflex exists in 66 p. 100 of the population studied in the ulnar nerve. Its latency is 11,1 msec; R = to Hmax/Mmax is equal to 30 p. 100. This reflex disappears progressively during the development."}
{"id": "PMID:205930", "title": "Hormonal stimulation of intestinal brush border enzymes release.", "content": "The rat small bowel was perfused in vivo and ex vivo in the absence of biliary and pancreatic secretion. Intraluminal release of sucrase, alkaline phosphatase, aminopeptidases and enterokinase was significantly increased after administration of pentagastrin, caerulein and glucagon at doses ranging between 1 pg and 10 microgram. This suggests that there is a direct hormonal stimulation of the intestinal mucosa. This effect might at least partly be mediated through cyclic AMP since dibutyryl derivates of this cyclic nucleotide exerted a significant stimulatory effect on intraluminal release of proteins, sucrase and enterokinase, although the pattern of enzyme was quite different from the effect produced by the three peptides.", "contents": "Hormonal stimulation of intestinal brush border enzymes release. The rat small bowel was perfused in vivo and ex vivo in the absence of biliary and pancreatic secretion. Intraluminal release of sucrase, alkaline phosphatase, aminopeptidases and enterokinase was significantly increased after administration of pentagastrin, caerulein and glucagon at doses ranging between 1 pg and 10 microgram. This suggests that there is a direct hormonal stimulation of the intestinal mucosa. This effect might at least partly be mediated through cyclic AMP since dibutyryl derivates of this cyclic nucleotide exerted a significant stimulatory effect on intraluminal release of proteins, sucrase and enterokinase, although the pattern of enzyme was quite different from the effect produced by the three peptides."}
{"id": "PMID:205931", "title": "[Proliferation of L 929 mouse fibroblasts and synthesis of active peptidyl prolyl hydroxylase in these cells in monolayer culture under the influence of D-penicillamine, azathioprine, aurothiopolypeptide, oxyphenbutazone and prednisolone (author's transl)].", "content": "L 929 mouse fibroblasts were cultured as monolayer using MEM Eagle medium after addition of bovine serum albumin, antibiotics, antimycotica, ferrous nitrate and ascorbic acid. In 24 hours distances cell number was counted. At the same time peptidyl prolyl hydroxylase activity was determined and related to the protein concentration in the cells. The proliferation of the cells followed a typical curve. The cell number decreased after trypsination, then increased logarithmically, finally reached a stationary phase. Enzyme activity showed a correspondent curve. Active enzyme did not appear until near the end of the log phase. After addition of the mesenchyme active substances in therapeutical concentrations proliferation and synthesis of active peptidyl prolyl hydroxylase in the cells were significantly decreased. The results are discussed in relation to the characteristics of collagen synthesis and proliferation of connective tissue cells under physiological, pathophysiological and therapeutical conditions.", "contents": "[Proliferation of L 929 mouse fibroblasts and synthesis of active peptidyl prolyl hydroxylase in these cells in monolayer culture under the influence of D-penicillamine, azathioprine, aurothiopolypeptide, oxyphenbutazone and prednisolone (author's transl)]. L 929 mouse fibroblasts were cultured as monolayer using MEM Eagle medium after addition of bovine serum albumin, antibiotics, antimycotica, ferrous nitrate and ascorbic acid. In 24 hours distances cell number was counted. At the same time peptidyl prolyl hydroxylase activity was determined and related to the protein concentration in the cells. The proliferation of the cells followed a typical curve. The cell number decreased after trypsination, then increased logarithmically, finally reached a stationary phase. Enzyme activity showed a correspondent curve. Active enzyme did not appear until near the end of the log phase. After addition of the mesenchyme active substances in therapeutical concentrations proliferation and synthesis of active peptidyl prolyl hydroxylase in the cells were significantly decreased. The results are discussed in relation to the characteristics of collagen synthesis and proliferation of connective tissue cells under physiological, pathophysiological and therapeutical conditions."}
{"id": "PMID:205932", "title": "Cyclic nucleotide metabolism in experimental bronchial constriction in rabbits.", "content": "In anesthetized, spontaneously breathing rabbits, intratracheally administered isotonic saline, acetylcholine (Ach) and histamine (His) induced an increase of airway resistance up to 183, 571, and 312%, respectively, compared with untreated controls. This was accompanied by a decrease of the arterial pO2. Bilateral cervical vagotomy led to nearly complete inhibition of the saline- and Ach-induced bronchoconstriction, whereas the His effect was only reduced to 202%. Vagotomy did not improve the arterial pO2. While the bronchoconstrictive effects of isotonic saline and Ach revealed a significant linear correlation with the increased cGMP/cAMP ratio, His did not cause an alteration of the cGMP/cAMP ratio to a degree that corresponds to its bronchoconstrictive activity. These data indicate that (1) bronchoconstriction-inducing agents may act (a) by stimulation of the parasympathetic nerve or (b) by contracting smooth muscles directly; (2) alveolar ventilation is not regulated by the parasympathetic nerve, and (3) bronchoconstriction induced by parasympathetic stimulation is associated with or mediated by an increase of the cGMP/cAMP ratio.", "contents": "Cyclic nucleotide metabolism in experimental bronchial constriction in rabbits. In anesthetized, spontaneously breathing rabbits, intratracheally administered isotonic saline, acetylcholine (Ach) and histamine (His) induced an increase of airway resistance up to 183, 571, and 312%, respectively, compared with untreated controls. This was accompanied by a decrease of the arterial pO2. Bilateral cervical vagotomy led to nearly complete inhibition of the saline- and Ach-induced bronchoconstriction, whereas the His effect was only reduced to 202%. Vagotomy did not improve the arterial pO2. While the bronchoconstrictive effects of isotonic saline and Ach revealed a significant linear correlation with the increased cGMP/cAMP ratio, His did not cause an alteration of the cGMP/cAMP ratio to a degree that corresponds to its bronchoconstrictive activity. These data indicate that (1) bronchoconstriction-inducing agents may act (a) by stimulation of the parasympathetic nerve or (b) by contracting smooth muscles directly; (2) alveolar ventilation is not regulated by the parasympathetic nerve, and (3) bronchoconstriction induced by parasympathetic stimulation is associated with or mediated by an increase of the cGMP/cAMP ratio."}
{"id": "PMID:205939", "title": "Bleeding from cecal ulcers in renal transplant patients.", "content": "Cecal ulcerations represent a high percentage of causes of gastrointestinal bleeding in renal transplant patients. A close association of these lesions with cytomegalovirus (CMV) infection has been found, even though a cause-effect relationship has not been established. All of these patients are usually critically ill, and a progressive deterioration leading to death is the rule. Our experience suggests that the decrease of immunosuppressive drug therapy, followed by the nephrectomy of the transplanted kidney if signs of rejection are present, and right hemicolectomy are the best therapy. Angiographic procedures are of importance to determine the site of bleeding, stabilize the bleeding with the use of vasoconstrictor drug therapy, and to plan the surgical treatment.", "contents": "Bleeding from cecal ulcers in renal transplant patients. Cecal ulcerations represent a high percentage of causes of gastrointestinal bleeding in renal transplant patients. A close association of these lesions with cytomegalovirus (CMV) infection has been found, even though a cause-effect relationship has not been established. All of these patients are usually critically ill, and a progressive deterioration leading to death is the rule. Our experience suggests that the decrease of immunosuppressive drug therapy, followed by the nephrectomy of the transplanted kidney if signs of rejection are present, and right hemicolectomy are the best therapy. Angiographic procedures are of importance to determine the site of bleeding, stabilize the bleeding with the use of vasoconstrictor drug therapy, and to plan the surgical treatment."}
{"id": "PMID:205940", "title": "Origin of intranuclear inclusions in myeloma cells.", "content": "The mechanism of inclusion of the cytoplasmic dense bodies into the nucleus of myeloma cells was studied by transmission electron microscopy. The findings in different cells suggest that the inclusion of the electron-dense bodies is a result of an interaction between the nuclear envelope and the endoplasmic reticulum. The ability of the nuclear membrane to form an extension into the cytoplasm and the connection with the cisternae of endoplasmic reticulum enables the movement of the dense bodies towards the nucleus. The proposed mechanism does not support the concept of a simple invagination of the bodies into the nucleus or that they are produced in the nucleus itself.", "contents": "Origin of intranuclear inclusions in myeloma cells. The mechanism of inclusion of the cytoplasmic dense bodies into the nucleus of myeloma cells was studied by transmission electron microscopy. The findings in different cells suggest that the inclusion of the electron-dense bodies is a result of an interaction between the nuclear envelope and the endoplasmic reticulum. The ability of the nuclear membrane to form an extension into the cytoplasm and the connection with the cisternae of endoplasmic reticulum enables the movement of the dense bodies towards the nucleus. The proposed mechanism does not support the concept of a simple invagination of the bodies into the nucleus or that they are produced in the nucleus itself."}
{"id": "PMID:205941", "title": "[C-cells of the thyroid gland].", "content": "In the human thyroid gland, the C-cell system reacts in physiologic and pathologic conditions as an entity and represents an independent endocrine organ. Its special features are its embryology, which relates it to other derivatives of the neural crest, the special histologic methods needed to demonstrate its disseminated C cells, and the obscure physiologic role of its hormone, calcitonin. Although there exist many histopathologic findings, the only C-cell disease of clinical interest is medullary carcinoma, which in its familial form is usually associated with pluriglandular syndromes.", "contents": "[C-cells of the thyroid gland]. In the human thyroid gland, the C-cell system reacts in physiologic and pathologic conditions as an entity and represents an independent endocrine organ. Its special features are its embryology, which relates it to other derivatives of the neural crest, the special histologic methods needed to demonstrate its disseminated C cells, and the obscure physiologic role of its hormone, calcitonin. Although there exist many histopathologic findings, the only C-cell disease of clinical interest is medullary carcinoma, which in its familial form is usually associated with pluriglandular syndromes."}
{"id": "PMID:205944", "title": "Highly reiterated sequences of SIMIANSIMIANSIMIANSIMIANSIMIAN.", "content": "A 172-base pair segment of DNA that is repeated several million times in the genome of the African green monkey has been characterized. Sequence analysis revealed that the many repeats of this complex unit are not all identical but represent a set of closely related segments: Sequence divergence occurs at various positions in the segment in a nonrandom manner. The uncloned segment obtained from monkey DNA is compared with a cloned segment of the same DNA which was recombined into the genome of simian virus 40 during permissive infection.", "contents": "Highly reiterated sequences of SIMIANSIMIANSIMIANSIMIANSIMIAN. A 172-base pair segment of DNA that is repeated several million times in the genome of the African green monkey has been characterized. Sequence analysis revealed that the many repeats of this complex unit are not all identical but represent a set of closely related segments: Sequence divergence occurs at various positions in the segment in a nonrandom manner. The uncloned segment obtained from monkey DNA is compared with a cloned segment of the same DNA which was recombined into the genome of simian virus 40 during permissive infection."}
{"id": "PMID:205945", "title": "Induction of stalk and spore cell differentiation by cyclic AMP in slugs of Dictyostelium discoideum.", "content": "Multicellular masses of the cellular slime mold Dictyostelium discoideum, under conditions which ordinarily suppress cell differentiation, develop clusters of stalk cells and spore cells when implanted with Sephadex particles that had been soaked in 5 X 10(-3)M cyclic adenosine monophosphate (AMP). A possible relation exists between oxygen gradients, cyclic AMP gradients, and the pattern of morphogenesis and cell differentiation during fruiting.", "contents": "Induction of stalk and spore cell differentiation by cyclic AMP in slugs of Dictyostelium discoideum. Multicellular masses of the cellular slime mold Dictyostelium discoideum, under conditions which ordinarily suppress cell differentiation, develop clusters of stalk cells and spore cells when implanted with Sephadex particles that had been soaked in 5 X 10(-3)M cyclic adenosine monophosphate (AMP). A possible relation exists between oxygen gradients, cyclic AMP gradients, and the pattern of morphogenesis and cell differentiation during fruiting."}
{"id": "PMID:205946", "title": "(S)-9-(2,3-Dihydroxypropyl)adenine: an aliphatic nucleoside analog with broad-spectrum antiviral activity.", "content": "(S)-9-(2,3-Dihydroxypropyl)adenine, a novel nucleoside analog, the sugar moiety of which is replaced by an aliphatic chain, inhibits the replication in vitro of several DNA and RNA viruses, including vaccinia, herpes simplex (types 1 and 2), measles, and vesicular stomatitis. It is also effective in vivo in reducing the mortality rate of mice inoculated intranasally with vesicular stomatitis virus.", "contents": "(S)-9-(2,3-Dihydroxypropyl)adenine: an aliphatic nucleoside analog with broad-spectrum antiviral activity. (S)-9-(2,3-Dihydroxypropyl)adenine, a novel nucleoside analog, the sugar moiety of which is replaced by an aliphatic chain, inhibits the replication in vitro of several DNA and RNA viruses, including vaccinia, herpes simplex (types 1 and 2), measles, and vesicular stomatitis. It is also effective in vivo in reducing the mortality rate of mice inoculated intranasally with vesicular stomatitis virus."}
{"id": "PMID:205947", "title": "The genome of simian virus 40.", "content": "The nucleotide sequence of SV40 DNA was determined, and the sequence was correlated with known genes of the virus and with the structure of viral messenger RNA's. There is a limited overlap of the coding regions for structural proteins and a complex pattern of leader sequences at the 5' end of late messenger RNA. The sequence of the early region is consistent with recent proposals that the large early polypeptide of SV40 is encoded in noncontinguous segments of DNA.", "contents": "The genome of simian virus 40. The nucleotide sequence of SV40 DNA was determined, and the sequence was correlated with known genes of the virus and with the structure of viral messenger RNA's. There is a limited overlap of the coding regions for structural proteins and a complex pattern of leader sequences at the 5' end of late messenger RNA. The sequence of the early region is consistent with recent proposals that the large early polypeptide of SV40 is encoded in noncontinguous segments of DNA."}
{"id": "PMID:205948", "title": "Cytochrome c oxidase as the receptor molecule for chemoaccumulation (chemotaxis) of Euglena toward oxygen.", "content": "Chemoaccumulation of Euglena gracilis toward oxygen was selectively inhibited, without concomitant effects on cell motility, by cyanide (10(-6) to 10(-4) molar) and carbon monoxide (5 x 10(-5) to 5 x 10(-4) molar). Above these concentrations, motility of the cell was imparied and the chemosensory response was inhibited. Azide did not affect chemoaccumulation even at 5 x 10(-3) molar. It is concluded that cytochrome a3 serves as the chemoreceptor molecule for oxygen-mediated behavioral responses in Euglena.", "contents": "Cytochrome c oxidase as the receptor molecule for chemoaccumulation (chemotaxis) of Euglena toward oxygen. Chemoaccumulation of Euglena gracilis toward oxygen was selectively inhibited, without concomitant effects on cell motility, by cyanide (10(-6) to 10(-4) molar) and carbon monoxide (5 x 10(-5) to 5 x 10(-4) molar). Above these concentrations, motility of the cell was imparied and the chemosensory response was inhibited. Azide did not affect chemoaccumulation even at 5 x 10(-3) molar. It is concluded that cytochrome a3 serves as the chemoreceptor molecule for oxygen-mediated behavioral responses in Euglena."}
{"id": "PMID:205949", "title": "Stimulation of dopamine synthesis in caudate nucleus by intrastriatal enkephalins and antagonism by naloxone.", "content": "The intraventricular injection of methionine-enkephalin (50 to 100 micrograms) or [d-Ala2]-methionine-enkephalinamide (1.5 to 12 micrograms), a synthetic enkephalin analog resistant to enzyme degradation, caused a marked dose-dependent increase in dihydroxyphenylacetic acid and homovanillic acid concentrations in the rat striatum. The [d-Ala2] analog increased the accumulation of dopa in the striatum after aromatic amino acid decarboxylase inhibition, indicating that it increased dopamine synthesis. At the highest doses used both enkephalins failed to modify brain serotonin metabolism. The monolateral microinjection of the [d-Ala2]] analog (3 to 6 micrograms) into the caudate nucleus increased the concentration of dihydroxyphenylacetic acid in the injected side, whereas bilateral injection increased the concentration of this compound in both caudate nuclei and caused catalepsy. The stimulant effect of the [d-Ala2] analog on dopamine synthesis in the striatum persisted after destruction of striatal postsynaptic dopamine receptors with kainic acid. The biochemical and behavioral effects of enkephalins were prevented by naloxone, a specific narcotic antagonist. The results indicate that enkephalins stimulate dopamine synthesis by an action on opioid receptors localized on dopaminergic nerve terminals.", "contents": "Stimulation of dopamine synthesis in caudate nucleus by intrastriatal enkephalins and antagonism by naloxone. The intraventricular injection of methionine-enkephalin (50 to 100 micrograms) or [d-Ala2]-methionine-enkephalinamide (1.5 to 12 micrograms), a synthetic enkephalin analog resistant to enzyme degradation, caused a marked dose-dependent increase in dihydroxyphenylacetic acid and homovanillic acid concentrations in the rat striatum. The [d-Ala2] analog increased the accumulation of dopa in the striatum after aromatic amino acid decarboxylase inhibition, indicating that it increased dopamine synthesis. At the highest doses used both enkephalins failed to modify brain serotonin metabolism. The monolateral microinjection of the [d-Ala2]] analog (3 to 6 micrograms) into the caudate nucleus increased the concentration of dihydroxyphenylacetic acid in the injected side, whereas bilateral injection increased the concentration of this compound in both caudate nuclei and caused catalepsy. The stimulant effect of the [d-Ala2] analog on dopamine synthesis in the striatum persisted after destruction of striatal postsynaptic dopamine receptors with kainic acid. The biochemical and behavioral effects of enkephalins were prevented by naloxone, a specific narcotic antagonist. The results indicate that enkephalins stimulate dopamine synthesis by an action on opioid receptors localized on dopaminergic nerve terminals."}
{"id": "PMID:205950", "title": "Chemotactic antibody.", "content": "Antibody of the immunoglobulin G class to herpes simplex virus and antibody of the immunoglobulin M class to sheep red blood cells were coupled to the synthetic peptide formylmethionylleucylphenylalanine (fMet-Leu-Phe), which is chemotactic for both mononuclear and polymorphonuclear leukocytes. The resulting molecules were chemotactic and retained their antigen-binding activity. When antibodies coupled to fMet-Leu-Phe were incubated with antigen, the resulting immune complexes were also chemotactic. Chemotactic antibody may provide a potent means of enhancing the migration of inflammatory cells to specific sites.", "contents": "Chemotactic antibody. Antibody of the immunoglobulin G class to herpes simplex virus and antibody of the immunoglobulin M class to sheep red blood cells were coupled to the synthetic peptide formylmethionylleucylphenylalanine (fMet-Leu-Phe), which is chemotactic for both mononuclear and polymorphonuclear leukocytes. The resulting molecules were chemotactic and retained their antigen-binding activity. When antibodies coupled to fMet-Leu-Phe were incubated with antigen, the resulting immune complexes were also chemotactic. Chemotactic antibody may provide a potent means of enhancing the migration of inflammatory cells to specific sites."}
{"id": "PMID:205951", "title": "Imprinting behavior: pituitary-adrenocortical modulation of the approach response.", "content": "Plasma corticosterone concentrations in newly hatched ducklings exposed to an imprinting model are inversely related to the strength of approach behavior. Injections of corticosterone before imprinting reduces following, whereas alpha1-10-adrenocorticotropin or antiserum to corticosterone augments following behavior. The sensitive period for imprinting may be regulated by changes in the pituitary-adrenocortical axis.", "contents": "Imprinting behavior: pituitary-adrenocortical modulation of the approach response. Plasma corticosterone concentrations in newly hatched ducklings exposed to an imprinting model are inversely related to the strength of approach behavior. Injections of corticosterone before imprinting reduces following, whereas alpha1-10-adrenocorticotropin or antiserum to corticosterone augments following behavior. The sensitive period for imprinting may be regulated by changes in the pituitary-adrenocortical axis."}
{"id": "PMID:205952", "title": "Collagenase immunolocalization in cultures of rheumatoid synovial cells.", "content": "Cultures of rheumatoid synovial cells that have been enzymatically dissociated and are adherent to a culture vessel are morphologically heterogeneous. When these cells are cultured on a collagenous substrate for 2 to 6 days at 37 degrees C in serum-free medium, they produce collagenase. A monospecific antibody to human collagenase has localized the enzyme extracellularly around cytoplasmic extensions of dendritic cells and intracellularly within a few macrophage-like and fibroblast-like cells.", "contents": "Collagenase immunolocalization in cultures of rheumatoid synovial cells. Cultures of rheumatoid synovial cells that have been enzymatically dissociated and are adherent to a culture vessel are morphologically heterogeneous. When these cells are cultured on a collagenous substrate for 2 to 6 days at 37 degrees C in serum-free medium, they produce collagenase. A monospecific antibody to human collagenase has localized the enzyme extracellularly around cytoplasmic extensions of dendritic cells and intracellularly within a few macrophage-like and fibroblast-like cells."}
{"id": "PMID:205953", "title": "Different actions of anticonvulsant and anesthetic barbiturates revealed by use of cultured mammalian neurons.", "content": "Barbiturate anesthetics, but not anticonvulsants, abolish the spontaneous activity of cultured spinal cord neurons; directly increase membrane conductance, an effect which is suppressed by the gamma-aminobutyric acid (GABA) antagonists picrotoxin and penicillin; and are more potent than anticonvulsants in augmenting GABA and depressing glutamate responses. Barbiturate anticonvulsants abolish picrotoxin-induced convulsive activity. These results indicate qualitative and quantitative differences between anesthetic and anticonvulsant barbiturates, which may explain their different clinical effects.", "contents": "Different actions of anticonvulsant and anesthetic barbiturates revealed by use of cultured mammalian neurons. Barbiturate anesthetics, but not anticonvulsants, abolish the spontaneous activity of cultured spinal cord neurons; directly increase membrane conductance, an effect which is suppressed by the gamma-aminobutyric acid (GABA) antagonists picrotoxin and penicillin; and are more potent than anticonvulsants in augmenting GABA and depressing glutamate responses. Barbiturate anticonvulsants abolish picrotoxin-induced convulsive activity. These results indicate qualitative and quantitative differences between anesthetic and anticonvulsant barbiturates, which may explain their different clinical effects."}
{"id": "PMID:205955", "title": "Common alcohol-related disorders: recognition and management.", "content": "Appropriate medical treatment of alcoholics often falls between the clinical specialties of psychiatry, internal medicine, toxicology, and neurology. All physicians need to have a high index of suspicion for alcoholism, since the diagnosis of alcohol dependence is frequently overlooked. Especially when alcoholics are self-referred to nonmedical agencies, their medical complications may be inadequately treated or unrecognized. Common alcohol-related complications requiring treatment include: (1) clinicopathologic disorders, often associated with the gastroenterologic or cardiorespiratory systems, including alcoholic cirrhosis, (2) peripheral myoneural effects, (3) neuropsychiatric complications (delirium tremens, acute alcoholic hallucinosis, Korsakoff's psychosis, alcoholic dementia), and (4) psychosocial disability.", "contents": "Common alcohol-related disorders: recognition and management. Appropriate medical treatment of alcoholics often falls between the clinical specialties of psychiatry, internal medicine, toxicology, and neurology. All physicians need to have a high index of suspicion for alcoholism, since the diagnosis of alcohol dependence is frequently overlooked. Especially when alcoholics are self-referred to nonmedical agencies, their medical complications may be inadequately treated or unrecognized. Common alcohol-related complications requiring treatment include: (1) clinicopathologic disorders, often associated with the gastroenterologic or cardiorespiratory systems, including alcoholic cirrhosis, (2) peripheral myoneural effects, (3) neuropsychiatric complications (delirium tremens, acute alcoholic hallucinosis, Korsakoff's psychosis, alcoholic dementia), and (4) psychosocial disability."}
{"id": "PMID:205956", "title": "Adhesive arachnoiditis following lumbar myelography.", "content": "Late sequelae (adhesive arachnoiditis) have been reported following myelography with the oily contrast medium (Pantopaque) and with the ionic water-soluble contrast media methiodal sodium (Abrodil, Conturex, Kontrast U) meglumine iothalamate (Conray Meglumine) and meglumine iocarmate (Bis-Conray, Dimer-X). Adhesive arachnoiditis has not yet been reported after the use of the nonionic water-soluble contrast medium metrizamide (Amipaque). Thus, this is considered the contrast medium of choice for lumbar myelography. Using the recommended dose of 10 ml with an iodine concentration of 170 mg/ml for this examination, adhesive arachnoiditis is unlikely to occur. Increased osmolality of spinal fluid after injection of contrast medium is related to increased frequency of arachnoiditis.", "contents": "Adhesive arachnoiditis following lumbar myelography. Late sequelae (adhesive arachnoiditis) have been reported following myelography with the oily contrast medium (Pantopaque) and with the ionic water-soluble contrast media methiodal sodium (Abrodil, Conturex, Kontrast U) meglumine iothalamate (Conray Meglumine) and meglumine iocarmate (Bis-Conray, Dimer-X). Adhesive arachnoiditis has not yet been reported after the use of the nonionic water-soluble contrast medium metrizamide (Amipaque). Thus, this is considered the contrast medium of choice for lumbar myelography. Using the recommended dose of 10 ml with an iodine concentration of 170 mg/ml for this examination, adhesive arachnoiditis is unlikely to occur. Increased osmolality of spinal fluid after injection of contrast medium is related to increased frequency of arachnoiditis."}
{"id": "PMID:205957", "title": "Lumbar myelography with amipaque.", "content": "In lumbar myelography, early side effects occur in about half the patients examined with modern water-soluble contrast media. At myelography with Amipaque (metrizamide) these reactions are usually minor, and serious adverse reactions are rare. In our own series of 650 consecutive lumbar myelographies with Amipaque there were no serious adverse effects. Minor adverse reactions occurred in 56% of the patients. Transient electroencephalogram (eeg) changes were seen in 14% of the patients, with only 5 patients showing paroxysmal spike activity. Adhesive arachnoiditis following lumbar myelography occurs significantly less often with Amipaque than with any other contrast medium. The properties of Amipaque provide excellent possibilities for detailed studies of all parts of the spinal subarachnoid space, and the medium constitutes a new and interesting aid for these investigations.", "contents": "Lumbar myelography with amipaque. In lumbar myelography, early side effects occur in about half the patients examined with modern water-soluble contrast media. At myelography with Amipaque (metrizamide) these reactions are usually minor, and serious adverse reactions are rare. In our own series of 650 consecutive lumbar myelographies with Amipaque there were no serious adverse effects. Minor adverse reactions occurred in 56% of the patients. Transient electroencephalogram (eeg) changes were seen in 14% of the patients, with only 5 patients showing paroxysmal spike activity. Adhesive arachnoiditis following lumbar myelography occurs significantly less often with Amipaque than with any other contrast medium. The properties of Amipaque provide excellent possibilities for detailed studies of all parts of the spinal subarachnoid space, and the medium constitutes a new and interesting aid for these investigations."}
{"id": "PMID:205962", "title": "Localization of insulinomas and islet cell hyperplasias by pancreatic vein catheterization and insulin assay.", "content": "Percutaneous transhepatic portal vein catheterization and transfemoral portal and caval catheterizations were performed under local anesthesia in five patients with symptoms of organic hypoglycemia. During the investigation, results of pancreatic phlebography revealed the pancreatic venous anatomy. Blood obtained from the celiac artery, caval branches and pancreatic veins was assayed for insulin by two different radioimmunoassay methods. Pathologically high, pancreatic arteriovenous insulin differences in two patients with insulinomas and in two patients with islet cell hyperplasia. In one of the patients with an insulinoma, one of the assays failed to detect the tumor insulin. This inconsistency still remains unexplained. Angiography revealed a pancreatic abnormality in only two patients. During operation, two of the tumors were found upon palpation and inspection. Pancreatic resections were performed according to the findings of pathologic hormone differences in all five patients. Immunocytochemistry revealed that three of the patients had insulin-producing tumors and two had local islet cell hyperplasia. Catheterizations performed two months postoperatively confirmed the radicality of the operation in all patients, with the possible exception of one patient. In one patient, a recurrance was detected by catheterization ten months postoperatively.", "contents": "Localization of insulinomas and islet cell hyperplasias by pancreatic vein catheterization and insulin assay. Percutaneous transhepatic portal vein catheterization and transfemoral portal and caval catheterizations were performed under local anesthesia in five patients with symptoms of organic hypoglycemia. During the investigation, results of pancreatic phlebography revealed the pancreatic venous anatomy. Blood obtained from the celiac artery, caval branches and pancreatic veins was assayed for insulin by two different radioimmunoassay methods. Pathologically high, pancreatic arteriovenous insulin differences in two patients with insulinomas and in two patients with islet cell hyperplasia. In one of the patients with an insulinoma, one of the assays failed to detect the tumor insulin. This inconsistency still remains unexplained. Angiography revealed a pancreatic abnormality in only two patients. During operation, two of the tumors were found upon palpation and inspection. Pancreatic resections were performed according to the findings of pathologic hormone differences in all five patients. Immunocytochemistry revealed that three of the patients had insulin-producing tumors and two had local islet cell hyperplasia. Catheterizations performed two months postoperatively confirmed the radicality of the operation in all patients, with the possible exception of one patient. In one patient, a recurrance was detected by catheterization ten months postoperatively."}
{"id": "PMID:205958", "title": "Inactivation of clinical isolates of Herpesvirus hominis, types 1 and 2, by chemical contraceptives.", "content": "Two chemical contraceptives were examined for virucidal effects against four strains each of Herpesvirus hominis, type 2 and 1. Seven of the strains represented recent clinical isolates; one strain was a type 2 prototype. Either psermicide reduced the infectivities ofall eight viruses after contact for 10 minutes at room or body temperature. The new spermicide-germicide, compound A, produced an antiviral effect at the low concentration of 0.05%, whereas the commercially available Preceptin was effective at 5%, but not at 0.5%. The substantial loss of viral infectivity was due to direct inactivation of virus by the spermicides and was not secondary to cytotoxicity or induction of interferon in the cell cultures used for the assay. These in vitro findings hold primse for the interruption of the sexual transmission of H. hominis.", "contents": "Inactivation of clinical isolates of Herpesvirus hominis, types 1 and 2, by chemical contraceptives. Two chemical contraceptives were examined for virucidal effects against four strains each of Herpesvirus hominis, type 2 and 1. Seven of the strains represented recent clinical isolates; one strain was a type 2 prototype. Either psermicide reduced the infectivities ofall eight viruses after contact for 10 minutes at room or body temperature. The new spermicide-germicide, compound A, produced an antiviral effect at the low concentration of 0.05%, whereas the commercially available Preceptin was effective at 5%, but not at 0.5%. The substantial loss of viral infectivity was due to direct inactivation of virus by the spermicides and was not secondary to cytotoxicity or induction of interferon in the cell cultures used for the assay. These in vitro findings hold primse for the interruption of the sexual transmission of H. hominis."}
{"id": "PMID:205963", "title": "Circulating immune complexes in patients following clinically curative resection of colorectal cancer.", "content": "Sixty-nine patients have been followed prospectively after curative resection of Dukes-Kirklin B-2 or C colorectal cancer. Serial plasma samples were studied in selected patients to determine changes in circulating immune complex concentrations (CIC) following primary tumor resection, and to compare serial plasma CIC and carcinoembryonic antigen (CEA) levels. CIC was determined in an average of seven serial samples per patient by inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC). CEA assays were performed by the Hanson Z-gel method. Two distinct patterns of serial CIC have emerged. In seven patients with no known tumor recurrences, serial CEA levels and CIC oscillated regularly and were inversely related. In seven of eight patients whose tumors recurred, both CEA and CIC rose together. In three patients with elevated plasma CEA levels due to inflammatory bowel disease, serial Ag-Ab complex concentrations did not vary, nor did separated Ag or Ab fractions inhibit ADCC. These data suggest that, in patients following curative resection of colorectal cancer, serial changes in circulating immune complexes may discriminate between transient CEA elevations which occur despite no known tumor recurrence and tumor recurrence which is beyond the capacity of adequate host antitumor defense.", "contents": "Circulating immune complexes in patients following clinically curative resection of colorectal cancer. Sixty-nine patients have been followed prospectively after curative resection of Dukes-Kirklin B-2 or C colorectal cancer. Serial plasma samples were studied in selected patients to determine changes in circulating immune complex concentrations (CIC) following primary tumor resection, and to compare serial plasma CIC and carcinoembryonic antigen (CEA) levels. CIC was determined in an average of seven serial samples per patient by inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC). CEA assays were performed by the Hanson Z-gel method. Two distinct patterns of serial CIC have emerged. In seven patients with no known tumor recurrences, serial CEA levels and CIC oscillated regularly and were inversely related. In seven of eight patients whose tumors recurred, both CEA and CIC rose together. In three patients with elevated plasma CEA levels due to inflammatory bowel disease, serial Ag-Ab complex concentrations did not vary, nor did separated Ag or Ab fractions inhibit ADCC. These data suggest that, in patients following curative resection of colorectal cancer, serial changes in circulating immune complexes may discriminate between transient CEA elevations which occur despite no known tumor recurrence and tumor recurrence which is beyond the capacity of adequate host antitumor defense."}
{"id": "PMID:205964", "title": "Display of epicardial ischemia by reduced nicotamide adenine dinucleotide fluorescence photography, electron microscopy, and ST segment mapping.", "content": "Reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography, a technique of assessing myocardial ischemia, was correlated with ischemia as identified by ST segment mapping and electron microscopy (EM) in 25 Langdneorff perfused rabbit hearts following coronary occlusion. Nicotinamide adenine dinucleotide (NAD), a component of the intramitochondrial electron transport chain, becomes reduced during periods of ischemia (NADH). NADH fluoresces when excited by ultraviolet light. NAD does not. All three techniques were compared to assess their resolution of the \"border zone\" between ischemia and nonischemic myocardium. The border zone defined by NADH fluorescence is 0.1 mm or less. Areas of high NADH fluorescence invariably revealed ST segment elevation, whereas minimally fluorescent areas did not. St segment mapping yields a border zone of approximately 7 mm. Areas of high NADH fluorescence following 1 hour of ischemia displayed severe damage on EM as compared to matched controls. A zone of intermediate ultrastructural damage is identified in a 1 mm biopsy taken between fluorescent and nonfluorescent myocardium. This evidence confirms epicardial NADH fluorescence photography as an assay of myocardial ischemia. This high resolution technique delineates a border zone of narrow dimensions as compared with ST segment mapping.", "contents": "Display of epicardial ischemia by reduced nicotamide adenine dinucleotide fluorescence photography, electron microscopy, and ST segment mapping. Reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography, a technique of assessing myocardial ischemia, was correlated with ischemia as identified by ST segment mapping and electron microscopy (EM) in 25 Langdneorff perfused rabbit hearts following coronary occlusion. Nicotinamide adenine dinucleotide (NAD), a component of the intramitochondrial electron transport chain, becomes reduced during periods of ischemia (NADH). NADH fluoresces when excited by ultraviolet light. NAD does not. All three techniques were compared to assess their resolution of the \"border zone\" between ischemia and nonischemic myocardium. The border zone defined by NADH fluorescence is 0.1 mm or less. Areas of high NADH fluorescence invariably revealed ST segment elevation, whereas minimally fluorescent areas did not. St segment mapping yields a border zone of approximately 7 mm. Areas of high NADH fluorescence following 1 hour of ischemia displayed severe damage on EM as compared to matched controls. A zone of intermediate ultrastructural damage is identified in a 1 mm biopsy taken between fluorescent and nonfluorescent myocardium. This evidence confirms epicardial NADH fluorescence photography as an assay of myocardial ischemia. This high resolution technique delineates a border zone of narrow dimensions as compared with ST segment mapping."}
{"id": "PMID:205971", "title": "Platelet aggregation and cyclic nucleotide phosphodiesterase activity in arteriosclerotic patients.", "content": "Although roles of roles of cyclic AMP and cyclic GMP in platelets are though to be important on platelet aggregation, little information on their phosphodiesterase (PDE) is available. Cyclic AMP and cyclic GMP hydrolytic activities of platelets (cAMPPDE and cGMPPDE in platelets) and platelet aggregation by ADP and adrenaline were measured in 22 healthy volunteers, 26 arteriosclerotic patients and other 20 miscellaneous patients excluding vascular diseases. Activities of cAMPPDE and cGMPPDE of platelets were 2.37 +/- 0.52, 7.23 +/- 1.84 in the healthy, 2.50 +/- 0.85, 7.53 +/- 2.60 in the arteriosclerotics and 2.38 +/- 1.02, 6.98 +/- 2.59 pmol/min/10(7) platelets in the miscellaneous patients, respectively. No significant difference was observed among these three groups. Platelet aggregabilities also showed no significant difference. However, there was a significant inverse correlation between the aggregability by 1 microgram/ml of adrenaline and the PDE activities only in the arteriosclerotic patients. The correlation coefficient were-0.61 between the primary aggregation and cAMPPDE,-0.65 between the primary aggregation and cGMPPDE,-0.58 between the 5 min aggregation and cAMPPDE and -0.76 between the 5 min aggregation and cGMPPDE. The inverse correlation between platelet aggregation and cyclic nucleotide metabolism in circulating platelts of the arteriosclerotic patients may suggest that interaction of platelets with arteriosclerotiv vessel walls would produce a certain change in platelets.", "contents": "Platelet aggregation and cyclic nucleotide phosphodiesterase activity in arteriosclerotic patients. Although roles of roles of cyclic AMP and cyclic GMP in platelets are though to be important on platelet aggregation, little information on their phosphodiesterase (PDE) is available. Cyclic AMP and cyclic GMP hydrolytic activities of platelets (cAMPPDE and cGMPPDE in platelets) and platelet aggregation by ADP and adrenaline were measured in 22 healthy volunteers, 26 arteriosclerotic patients and other 20 miscellaneous patients excluding vascular diseases. Activities of cAMPPDE and cGMPPDE of platelets were 2.37 +/- 0.52, 7.23 +/- 1.84 in the healthy, 2.50 +/- 0.85, 7.53 +/- 2.60 in the arteriosclerotics and 2.38 +/- 1.02, 6.98 +/- 2.59 pmol/min/10(7) platelets in the miscellaneous patients, respectively. No significant difference was observed among these three groups. Platelet aggregabilities also showed no significant difference. However, there was a significant inverse correlation between the aggregability by 1 microgram/ml of adrenaline and the PDE activities only in the arteriosclerotic patients. The correlation coefficient were-0.61 between the primary aggregation and cAMPPDE,-0.65 between the primary aggregation and cGMPPDE,-0.58 between the 5 min aggregation and cAMPPDE and -0.76 between the 5 min aggregation and cGMPPDE. The inverse correlation between platelet aggregation and cyclic nucleotide metabolism in circulating platelts of the arteriosclerotic patients may suggest that interaction of platelets with arteriosclerotiv vessel walls would produce a certain change in platelets."}
{"id": "PMID:205972", "title": "The effect of mitomycin C on platelet aggregation and adenosine 3',5'-monophosphate metabolism.", "content": "The effect of Mitomycin C on aggregation, adenosine 3',5'-monophosphate (cyclic AMP) metabolism and reactions induced by thrombin was studied in rabbit platelets. Mitomycin C inhibited the platelet aggregation induced by adenosine diphosphate or thrombin. The level of radioactive cyclic AMP derived from 8-14C adenine or 8-14C adenosine increased after incubating intact platelets with Mitomycin C. Formation of radioactive adenosine triphosphate also increased though mitochondrial oxidation was not stimulated. Similar effect was observed also in rabbit liver. Mitomycin C failed to stimulate platelet adenyl cyclase but inhibited cyclic AMP phosphodiesterase in the absence of theophylline. In the platelets preincubated with Mitomycin C, thrombin-induced inhibition of adenyl cyclase, stimulation of membrane-bound cyclic AMP phosphodiesterase, and release of 250,000 dalton protein from platelet membranes were prevented. These results suggest that Mitomycin C will affect cellular membrane structure and function, and this extranuclear effect of Mitomycin C will lead to inhibition of aggregation in blood platelets.", "contents": "The effect of mitomycin C on platelet aggregation and adenosine 3',5'-monophosphate metabolism. The effect of Mitomycin C on aggregation, adenosine 3',5'-monophosphate (cyclic AMP) metabolism and reactions induced by thrombin was studied in rabbit platelets. Mitomycin C inhibited the platelet aggregation induced by adenosine diphosphate or thrombin. The level of radioactive cyclic AMP derived from 8-14C adenine or 8-14C adenosine increased after incubating intact platelets with Mitomycin C. Formation of radioactive adenosine triphosphate also increased though mitochondrial oxidation was not stimulated. Similar effect was observed also in rabbit liver. Mitomycin C failed to stimulate platelet adenyl cyclase but inhibited cyclic AMP phosphodiesterase in the absence of theophylline. In the platelets preincubated with Mitomycin C, thrombin-induced inhibition of adenyl cyclase, stimulation of membrane-bound cyclic AMP phosphodiesterase, and release of 250,000 dalton protein from platelet membranes were prevented. These results suggest that Mitomycin C will affect cellular membrane structure and function, and this extranuclear effect of Mitomycin C will lead to inhibition of aggregation in blood platelets."}
{"id": "PMID:205975", "title": "Investigations on the modification of postirradiation pancreatic lipase activity by some endo- or exogenic factors. Part I. The influence of some agonists of adrenergic system.", "content": "The role of some agonists of the adrenergic system and inhibitors of phosphodiesterase activity in the modulation of the degree of lipase release from pancreatic granular fraction (zymogen and lysosomes) of control and X-ray irradiated rats was investigated. It was shown the decrease of the release of enzymatic activity under the influence of cyclic adenosine monophosphate (cAMP) and noradrenaline (NA) in the fractions from both investigated groups. Effects were dependent on the concentration used. Isoprenaline evoked opposite changes in control and irradiated specimens. In controls it facilitated the enzyme release when applied in smaller (10(-8)M) concentration. In granules from irradiated animals the decrease of enzyme release was noted under the influence of greater concentration (10(-6)M) of the drug. The action of papaverine was nearly similar in control and irradiated groups. The drug evoked the decrease or increase of enzyme release when applied in greater (10(-6)M) or smaller (10(-8)M) concentration respectively. Lipase release was markedly enhanced in controls by theophylline (both concentrations); in specimens from irradiated pancreas, however, no significant alterations were observed.", "contents": "Investigations on the modification of postirradiation pancreatic lipase activity by some endo- or exogenic factors. Part I. The influence of some agonists of adrenergic system. The role of some agonists of the adrenergic system and inhibitors of phosphodiesterase activity in the modulation of the degree of lipase release from pancreatic granular fraction (zymogen and lysosomes) of control and X-ray irradiated rats was investigated. It was shown the decrease of the release of enzymatic activity under the influence of cyclic adenosine monophosphate (cAMP) and noradrenaline (NA) in the fractions from both investigated groups. Effects were dependent on the concentration used. Isoprenaline evoked opposite changes in control and irradiated specimens. In controls it facilitated the enzyme release when applied in smaller (10(-8)M) concentration. In granules from irradiated animals the decrease of enzyme release was noted under the influence of greater concentration (10(-6)M) of the drug. The action of papaverine was nearly similar in control and irradiated groups. The drug evoked the decrease or increase of enzyme release when applied in greater (10(-6)M) or smaller (10(-8)M) concentration respectively. Lipase release was markedly enhanced in controls by theophylline (both concentrations); in specimens from irradiated pancreas, however, no significant alterations were observed."}
{"id": "PMID:205977", "title": "A simple technique to assess the total number of Onchocerca volvulus microfilariae in skin snips.", "content": "A technique for the assessment of the total number of microfilariae in skin snips from onchocerciasis patients is described. For the digestion of the skin tissue the biopsies are incubated at room temperature for 24 hours in medium 199, containing 3 mg/ml collagenase and antibiotics. This process leaves the microfilariae unharmed. A comparative study of the emergence of the microfilariae in different media showed that only 20% of the total number were released after 30 minutes in distilled water. After 24 hours incubation in isotonic saline 80% were found.", "contents": "A simple technique to assess the total number of Onchocerca volvulus microfilariae in skin snips. A technique for the assessment of the total number of microfilariae in skin snips from onchocerciasis patients is described. For the digestion of the skin tissue the biopsies are incubated at room temperature for 24 hours in medium 199, containing 3 mg/ml collagenase and antibiotics. This process leaves the microfilariae unharmed. A comparative study of the emergence of the microfilariae in different media showed that only 20% of the total number were released after 30 minutes in distilled water. After 24 hours incubation in isotonic saline 80% were found."}
{"id": "PMID:205979", "title": "Structure of human hemoglobin messenger RNA and its relation to hemoglobinopathies.", "content": "1. One-fifth to 1/4 of globin mRNA is untranslated sequence other than polyadenylic acid. 2. The untranslated sequences of mRNA vary markedly in their sequence and in their length. 3. Globin mRNAs demonstrate a marked bias in codon selection. 4. Viral mRNA shows a quite different pattern of codon selection; therefore, the selection of codons is not uniform for all mRNAs functioning in animal cells. 5. Elongated hemoglobin chains can be accounted for by frame-shift mutations, or point mutations within the normal termination codon. The additional amino acids are then coded for by sequences that are normally untranslated. 6. Certain hemoglobin deletion mutants occur at sites where there are partially reiterated sequences within the heomoglobin messenger RNA.", "contents": "Structure of human hemoglobin messenger RNA and its relation to hemoglobinopathies. 1. One-fifth to 1/4 of globin mRNA is untranslated sequence other than polyadenylic acid. 2. The untranslated sequences of mRNA vary markedly in their sequence and in their length. 3. Globin mRNAs demonstrate a marked bias in codon selection. 4. Viral mRNA shows a quite different pattern of codon selection; therefore, the selection of codons is not uniform for all mRNAs functioning in animal cells. 5. Elongated hemoglobin chains can be accounted for by frame-shift mutations, or point mutations within the normal termination codon. The additional amino acids are then coded for by sequences that are normally untranslated. 6. Certain hemoglobin deletion mutants occur at sites where there are partially reiterated sequences within the heomoglobin messenger RNA."}
{"id": "PMID:205983", "title": "The immediate pressor response to saralasin: a measure of the degree of angiotensin II vascular receptor vacancy.", "content": "(1) An immediate pressor response so saralasin, 10 microgram/kg/min, occurred in 52 of 57 (91%) hypertensive patients. (2) We propose that the amplitude of the immediate pressor response functions as an in vivo measure of the number of initially vacan angiotensin II vascular receptors. (3) The immediate pressor response to saralasin forecasts the subsequent sustained response, both of which are related to the renin-sodium profile. (4) The dual blood pressure responses to saralasin, immediate and sustained, make this drug useful for the pharmacological identification of high, normal, and low renin hypertensive patients as they are presently classified. (5) The ability of saralasin to elevate the BP immediately in most hypertensive patients shows the need for caution in its use. It is a safe drug from this standpoint if very small infusions (0.01-0.10 microgram/kg/min) are first tried in hypertensive patients whose PRA is unknown.", "contents": "The immediate pressor response to saralasin: a measure of the degree of angiotensin II vascular receptor vacancy. (1) An immediate pressor response so saralasin, 10 microgram/kg/min, occurred in 52 of 57 (91%) hypertensive patients. (2) We propose that the amplitude of the immediate pressor response functions as an in vivo measure of the number of initially vacan angiotensin II vascular receptors. (3) The immediate pressor response to saralasin forecasts the subsequent sustained response, both of which are related to the renin-sodium profile. (4) The dual blood pressure responses to saralasin, immediate and sustained, make this drug useful for the pharmacological identification of high, normal, and low renin hypertensive patients as they are presently classified. (5) The ability of saralasin to elevate the BP immediately in most hypertensive patients shows the need for caution in its use. It is a safe drug from this standpoint if very small infusions (0.01-0.10 microgram/kg/min) are first tried in hypertensive patients whose PRA is unknown."}
{"id": "PMID:205988", "title": "The immunoprophylaxis of of rotavirus infections in lambs.", "content": "The effect of colostrum or serum feeding on subsequent rotavirus infections was investigated in neonatal gnotobiotic lambs. Immunity after feeding colostrum did not depend on absorption of passively acquired antibody into the circulation. Protection against clinical disease depended on the volume of colostrum ingested. The protection afforded by feeding serum was specific, since serum free of rotavirus antibody failed to confer protection. Immune serum fed at a rate of 2.5 ml per kg twice daily protected against rotavirus infection. Also, it was shown by intraperitoneal inoculation of immune serum that protection could occur in the absence of ingested antibody, presumably by transfer of antibody into the gut. The implications of these findings for immunoprophylaxis of rotavirus diarrhoea in lambs and calves are discussed.", "contents": "The immunoprophylaxis of of rotavirus infections in lambs. The effect of colostrum or serum feeding on subsequent rotavirus infections was investigated in neonatal gnotobiotic lambs. Immunity after feeding colostrum did not depend on absorption of passively acquired antibody into the circulation. Protection against clinical disease depended on the volume of colostrum ingested. The protection afforded by feeding serum was specific, since serum free of rotavirus antibody failed to confer protection. Immune serum fed at a rate of 2.5 ml per kg twice daily protected against rotavirus infection. Also, it was shown by intraperitoneal inoculation of immune serum that protection could occur in the absence of ingested antibody, presumably by transfer of antibody into the gut. The implications of these findings for immunoprophylaxis of rotavirus diarrhoea in lambs and calves are discussed."}
{"id": "PMID:205993", "title": "Demonstration of argyrophil granules in small cell carcinoma of the lung.", "content": "The Grimelius silver nitrate stain has enabled us to demonstrate the presence of tumor cells with argyrophil granules (argyrophil cells) in small cell carcinoma of the lung. Of the 22 tumors, 11 showed varying numbers of argyrophil cells. The occurrence of the cells differed in frequency among the subtypes of small cell carcinoma. The fusiform cell type showed the cells more frequently than the other types. Both tumors with numerous argyrophil cells belonged to the fusiform cell type. The number of positive cells seen under the light microscope did not correlate with the number of cells containing neurosecretory granules under the electron microscope, nor with the amount of either ACTH or serotonin in the tumor extracts. The demonstration of these cells in a pulmonary carcinoma may be of help in making correct histological diagnosis.", "contents": "Demonstration of argyrophil granules in small cell carcinoma of the lung. The Grimelius silver nitrate stain has enabled us to demonstrate the presence of tumor cells with argyrophil granules (argyrophil cells) in small cell carcinoma of the lung. Of the 22 tumors, 11 showed varying numbers of argyrophil cells. The occurrence of the cells differed in frequency among the subtypes of small cell carcinoma. The fusiform cell type showed the cells more frequently than the other types. Both tumors with numerous argyrophil cells belonged to the fusiform cell type. The number of positive cells seen under the light microscope did not correlate with the number of cells containing neurosecretory granules under the electron microscope, nor with the amount of either ACTH or serotonin in the tumor extracts. The demonstration of these cells in a pulmonary carcinoma may be of help in making correct histological diagnosis."}
{"id": "PMID:205994", "title": "Ultrastructural aspects of corneal fibrous tissue in the Scheie syndrome.", "content": "An ultrastructural study of the corneal fibrous tissue was performed in a case of Scheie's syndrome. Mucopolysaccharidosis deposits in keratocytes were observed as electron-clear and electron-dense inclusions. Modifications of the extracellular space included modifications of lamellar collagen organization and local hypertrophy of collagen bundles; presence of microfibrillar dense material isolating large irregular collagen fibers; and presence of fibrous long spacing type collagen fibers. The significance of these changes is discussed. This special form of collagen organization is supposed to appear in a modified microenvironment, that is the presence of an abnormal concentration of proteoglycans.", "contents": "Ultrastructural aspects of corneal fibrous tissue in the Scheie syndrome. An ultrastructural study of the corneal fibrous tissue was performed in a case of Scheie's syndrome. Mucopolysaccharidosis deposits in keratocytes were observed as electron-clear and electron-dense inclusions. Modifications of the extracellular space included modifications of lamellar collagen organization and local hypertrophy of collagen bundles; presence of microfibrillar dense material isolating large irregular collagen fibers; and presence of fibrous long spacing type collagen fibers. The significance of these changes is discussed. This special form of collagen organization is supposed to appear in a modified microenvironment, that is the presence of an abnormal concentration of proteoglycans."}
{"id": "PMID:206004", "title": "Virus-specific early RNA in 3T6 cells infected by a tsA mutant of polyoma virus.", "content": "The accumulation of virus-specific early RNA in mouse 3T6 cells infected by wild type polyoma virus or by a tsA mutant, tsA25E, was measured by hybridization of cytoplasmic RNA to radiolabeled \"early\" strand polyoma DNA. Cells infected by the tsA25E mutant accumulated approximately 20 times more virus-specific early RNA during the early phase of lytic infection than did wild type-infected cells at both the permissive and the nonpermissive temperature under identical conditions of infection and hybridization. Cells infected by the tsA25E mutant at the permissive temperature continued to accumulate virus-specific early RNA during the late phase of infection after being shifted to the nonpermissive temperature to block further viral DNA replication. A mixed infection of cells by wild-type polyoma and tsA25E showed that the overproduction of early RNA by the tsA mutant alone could be suppressed by coinfection with the wild type. The results suggest that the A gene product of polyoma regulates transcription of early RNA, as has been suggested for SV40 (Reed et al., 1976) and that the wild-type A-gene product overcomes the effect of the temperature-sensitive A-gene product.", "contents": "Virus-specific early RNA in 3T6 cells infected by a tsA mutant of polyoma virus. The accumulation of virus-specific early RNA in mouse 3T6 cells infected by wild type polyoma virus or by a tsA mutant, tsA25E, was measured by hybridization of cytoplasmic RNA to radiolabeled \"early\" strand polyoma DNA. Cells infected by the tsA25E mutant accumulated approximately 20 times more virus-specific early RNA during the early phase of lytic infection than did wild type-infected cells at both the permissive and the nonpermissive temperature under identical conditions of infection and hybridization. Cells infected by the tsA25E mutant at the permissive temperature continued to accumulate virus-specific early RNA during the late phase of infection after being shifted to the nonpermissive temperature to block further viral DNA replication. A mixed infection of cells by wild-type polyoma and tsA25E showed that the overproduction of early RNA by the tsA mutant alone could be suppressed by coinfection with the wild type. The results suggest that the A gene product of polyoma regulates transcription of early RNA, as has been suggested for SV40 (Reed et al., 1976) and that the wild-type A-gene product overcomes the effect of the temperature-sensitive A-gene product."}
{"id": "PMID:206019", "title": "[Factors influencing the results of treating trophoblastic tumor patients].", "content": "To assess prognostic factors the author has analysed the clinical data on 127 patients, subjected to three variants of the treatment (chemotherapy - in 72, surgery+chemotherapy - in 34, surgery+chemotherapy+radiotherapy - in 21). The following factors have been examined: patients' age, a duration of the affection symptoms in relation to their pregnancy prior to the disease, issues of pregnancy preceding the disease, the size of the primary focus (the uterus), the degree of the process spread, the height of the CH level in diurnal urine before the treatment, the method of initial therapy. Based on the data obtained, it was demonstrated that aside of the tumor morphological structure and the extent of the process spread the results of the treatment are influenced by a sum of clinical signs of the disease, which shound in prognostication.", "contents": "[Factors influencing the results of treating trophoblastic tumor patients]. To assess prognostic factors the author has analysed the clinical data on 127 patients, subjected to three variants of the treatment (chemotherapy - in 72, surgery+chemotherapy - in 34, surgery+chemotherapy+radiotherapy - in 21). The following factors have been examined: patients' age, a duration of the affection symptoms in relation to their pregnancy prior to the disease, issues of pregnancy preceding the disease, the size of the primary focus (the uterus), the degree of the process spread, the height of the CH level in diurnal urine before the treatment, the method of initial therapy. Based on the data obtained, it was demonstrated that aside of the tumor morphological structure and the extent of the process spread the results of the treatment are influenced by a sum of clinical signs of the disease, which shound in prognostication."}
{"id": "PMID:206020", "title": "[Conservative operations in malignant I-stage ovarian tumors].", "content": "The remote results of conservative operations in 16 patients with malignant ovarian tumors stage I are reported and compared with the results of treatment following radical (38) and nonradical (45) operations. Two thirds of conservatively operated patients (unilateral adnexectomy) survived for more than 5 years, over 50% of patients showed a 10-year survival. It is emphasized that saving operative procedures should not be performed in the presence of the factors aggravating the prognosis (proliferation of the tumor capsule, adhesions, a ruptured tumor capsule).", "contents": "[Conservative operations in malignant I-stage ovarian tumors]. The remote results of conservative operations in 16 patients with malignant ovarian tumors stage I are reported and compared with the results of treatment following radical (38) and nonradical (45) operations. Two thirds of conservatively operated patients (unilateral adnexectomy) survived for more than 5 years, over 50% of patients showed a 10-year survival. It is emphasized that saving operative procedures should not be performed in the presence of the factors aggravating the prognosis (proliferation of the tumor capsule, adhesions, a ruptured tumor capsule)."}
{"id": "PMID:206028", "title": "[A preliminary report of \"selective ultraviolet phototherapy\" in psoriasis (author's transl)].", "content": "35 patients with psoriasis were treated solely by UV irradiation using a Saalmann selective ultraviolet phototherapy lamp (SUP), a mercury lamp with increased emission between 310 and 320 nm. Irradiation four to five times weekly produced 90 to 100% improvement in 83% of the patients. Nineteen of the thus-treated patients showed complete clearing of the psoriatic lesions. The average duration of treatment was 4 weeks. These good results were maintained on a regimen of twice-weekly UV therapy.", "contents": "[A preliminary report of \"selective ultraviolet phototherapy\" in psoriasis (author's transl)]. 35 patients with psoriasis were treated solely by UV irradiation using a Saalmann selective ultraviolet phototherapy lamp (SUP), a mercury lamp with increased emission between 310 and 320 nm. Irradiation four to five times weekly produced 90 to 100% improvement in 83% of the patients. Nineteen of the thus-treated patients showed complete clearing of the psoriatic lesions. The average duration of treatment was 4 weeks. These good results were maintained on a regimen of twice-weekly UV therapy."}
{"id": "PMID:206023", "title": "[Use of collalytine for preparation of monolayer primary cell cultures].", "content": "Collalytine, a national preparation of collagenase effect, may be used for dispersion of different organs of cattle and human fetuses. Depending on the concentration and time of treatment, this preparation permits to produce monolayer cultures of histotypic or cytotypic nature.", "contents": "[Use of collalytine for preparation of monolayer primary cell cultures]. Collalytine, a national preparation of collagenase effect, may be used for dispersion of different organs of cattle and human fetuses. Depending on the concentration and time of treatment, this preparation permits to produce monolayer cultures of histotypic or cytotypic nature."}
{"id": "PMID:206029", "title": "[Hyperlipemic arthropathy in primary hyperlipoproteinemia].", "content": "In this paper a case of hyperlipaemic arthropathy with participation of the skin in primary hyperlipoproteinaemia type IIa after Fredrickson is described. The case in question is a clinical picture which is very rarely described. Questions of differential diagnosis and genesis are discussed. The prognosis is to be estimated favourably when the basic disease is recognized and treated. The genesis of the disease is not yet clear. With the help of literature several possibilities of the development are discussed.", "contents": "[Hyperlipemic arthropathy in primary hyperlipoproteinemia]. In this paper a case of hyperlipaemic arthropathy with participation of the skin in primary hyperlipoproteinaemia type IIa after Fredrickson is described. The case in question is a clinical picture which is very rarely described. Questions of differential diagnosis and genesis are discussed. The prognosis is to be estimated favourably when the basic disease is recognized and treated. The genesis of the disease is not yet clear. With the help of literature several possibilities of the development are discussed."}
{"id": "PMID:206030", "title": "[Polypous nonchromaffin paraganglioma of the stomach].", "content": "It is reported on the unusual position of a nonchromaffin paraganglioma in the stomach, which in gastroscopy imposed as polyp and was removed. On the basis of the light-microscopic picture, its behaviour during staining and the electronmicroscopic investigations the tumour is classified in the group of the paragangliomata. Since there are no unequivocal histological criteria of malignity, on account of the well-known slow growth of these tumour only the polyp is removed.", "contents": "[Polypous nonchromaffin paraganglioma of the stomach]. It is reported on the unusual position of a nonchromaffin paraganglioma in the stomach, which in gastroscopy imposed as polyp and was removed. On the basis of the light-microscopic picture, its behaviour during staining and the electronmicroscopic investigations the tumour is classified in the group of the paragangliomata. Since there are no unequivocal histological criteria of malignity, on account of the well-known slow growth of these tumour only the polyp is removed."}
{"id": "PMID:206031", "title": "Carbohydrate composition of peripheral, cultured and leukaemic human lymphocyte plasma membranes.", "content": "Plasma membranes isolated from peripheral blood lymphocytes of normal donors, lymphocytes from patients with chronic lymphatic leukaemia (CLL), a T cell and B cell line (MOLT-3 and RPMI-1788) were analysed and compared for total carbohydrate contents. T cells and peripheral blood lymphocytes contained the highest relative amounts of sialic acid and fucose, whereas chronic lymphatic leukaemic cells possessed the highest amounts of N-acetylgalactosamine and also more total cell surface carbohydrate. The Thomsen-Friedenreich antigen (TF) was detected serologically on membrane fractions by the use of anti-TF containing sera and specific lectins from Arachis hypogaea, Agaricus bisporus and Vicia graminea. The disaccharide beta-D-galactosyl(1-3)-N-acetyl-D-galactosamine is the immunogdominant carbohydrate group of the FT antigen and was detected as its reduced form, by gas chromatography, in all cells, thus correlating serological and analytical evidence. The haemagglutinating activity of the lectins and sera used was only inhibited by plasma membranes after the removal of sialic acid showong that the native form of this antigen is normally masked by sialic acid in CLL cells as well as normal lymphocytes.", "contents": "Carbohydrate composition of peripheral, cultured and leukaemic human lymphocyte plasma membranes. Plasma membranes isolated from peripheral blood lymphocytes of normal donors, lymphocytes from patients with chronic lymphatic leukaemia (CLL), a T cell and B cell line (MOLT-3 and RPMI-1788) were analysed and compared for total carbohydrate contents. T cells and peripheral blood lymphocytes contained the highest relative amounts of sialic acid and fucose, whereas chronic lymphatic leukaemic cells possessed the highest amounts of N-acetylgalactosamine and also more total cell surface carbohydrate. The Thomsen-Friedenreich antigen (TF) was detected serologically on membrane fractions by the use of anti-TF containing sera and specific lectins from Arachis hypogaea, Agaricus bisporus and Vicia graminea. The disaccharide beta-D-galactosyl(1-3)-N-acetyl-D-galactosamine is the immunogdominant carbohydrate group of the FT antigen and was detected as its reduced form, by gas chromatography, in all cells, thus correlating serological and analytical evidence. The haemagglutinating activity of the lectins and sera used was only inhibited by plasma membranes after the removal of sialic acid showong that the native form of this antigen is normally masked by sialic acid in CLL cells as well as normal lymphocytes."}
{"id": "PMID:206026", "title": "[Mechanism of specific vaccine therapy in ocular herpes simplex].", "content": "The mechanism of specific vaccine therapy in herpetic eye disease was studied. The effectiveness of the therapy in the observation period of 3 to 8 years was established. In 71 (62%) of 114 patients relapses of the disease disappeared completely, in 32 (26%) became less frequent and in 11 (10%) their frequency did not change. The clinical course of relapses in all cases became milder. The vaccination courses given were shown not to influence the level of virusneutralizing antibody but to induce the appearance in the lacrimal fluid of immunoglobulins G and M and to increase considerably the level of IgA. The vaccint therapy enhanced the reactions of cell-mediated immunity which was manifested in increased specific blasttransformation of lymphocytes (up to 18%) and reduced the migrational capacity of leucocytes to inactivated antigen of herpesvirus. The effect of the vaccine persisted only for a few months. The immunological and clinical analyses showed that it was expedient to give vaccine in courses at 6--12-month intervals after an attack of herpes.", "contents": "[Mechanism of specific vaccine therapy in ocular herpes simplex]. The mechanism of specific vaccine therapy in herpetic eye disease was studied. The effectiveness of the therapy in the observation period of 3 to 8 years was established. In 71 (62%) of 114 patients relapses of the disease disappeared completely, in 32 (26%) became less frequent and in 11 (10%) their frequency did not change. The clinical course of relapses in all cases became milder. The vaccination courses given were shown not to influence the level of virusneutralizing antibody but to induce the appearance in the lacrimal fluid of immunoglobulins G and M and to increase considerably the level of IgA. The vaccint therapy enhanced the reactions of cell-mediated immunity which was manifested in increased specific blasttransformation of lymphocytes (up to 18%) and reduced the migrational capacity of leucocytes to inactivated antigen of herpesvirus. The effect of the vaccine persisted only for a few months. The immunological and clinical analyses showed that it was expedient to give vaccine in courses at 6--12-month intervals after an attack of herpes."}
{"id": "PMID:206027", "title": "[Pathomorphology of experimental infection caused by powassan virus isolated in the Primorski\u012d Territory].", "content": "Pathomorphology of the infection caused by Powassan virus strains isolated in the Primorsky Kray was studied in white mice. The central nervous system of the animals sacrificed in the time course of the infectious process was studied by light and luminescent microscopy. Severe diffuse inflammatory-degenerative changes were found in the brain and spinal cord. Immunofluorescence revealed cytoplasmic localization of the virus antigen in neurons, glial and connective tissue cells.", "contents": "[Pathomorphology of experimental infection caused by powassan virus isolated in the Primorski\u012d Territory]. Pathomorphology of the infection caused by Powassan virus strains isolated in the Primorsky Kray was studied in white mice. The central nervous system of the animals sacrificed in the time course of the infectious process was studied by light and luminescent microscopy. Severe diffuse inflammatory-degenerative changes were found in the brain and spinal cord. Immunofluorescence revealed cytoplasmic localization of the virus antigen in neurons, glial and connective tissue cells."}
{"id": "PMID:206072", "title": "[Aftercare of patients operated on for goiter (author's transl)].", "content": "Between 1966 to 1976 2122 patients underwent a partial thyroidectomy for goiter. All patients received special aftercare in the outpatient department of the hospital. Without hormonal substitution there were 5,9% relapses.", "contents": "[Aftercare of patients operated on for goiter (author's transl)]. Between 1966 to 1976 2122 patients underwent a partial thyroidectomy for goiter. All patients received special aftercare in the outpatient department of the hospital. Without hormonal substitution there were 5,9% relapses."}
{"id": "PMID:206074", "title": "[Diseases of the lumbosacral portion of the peripheral nervous system (treatment and prevention)].", "content": "A critical analysis of modern literature and personal experience permits the author in a discussional aspect to speak on diagnosis formulation in patients with lesions of the sacrolumbar area of the peripheral nervous system. The paper contains detailed recommendations in relation to different forms of medicative therapy and prevention in this group of patients. The subsequent perspectives and further studies, as well as organizational questions are being discussed.", "contents": "[Diseases of the lumbosacral portion of the peripheral nervous system (treatment and prevention)]. A critical analysis of modern literature and personal experience permits the author in a discussional aspect to speak on diagnosis formulation in patients with lesions of the sacrolumbar area of the peripheral nervous system. The paper contains detailed recommendations in relation to different forms of medicative therapy and prevention in this group of patients. The subsequent perspectives and further studies, as well as organizational questions are being discussed."}
{"id": "PMID:206075", "title": "Purification and properties of pig kidney glutamate dehydrogenase.", "content": "Glutamate dehydrogenase from pig kidney has been purified to homogeneity by means of affinity chromatography on matrix bound Cibacron Blue F3G-A and gel chromatography on Sepharose 6B. The enzyme exhibits allosteric properties with the substrates alpha-ketoglutarate, ammonium, and NADH, respectively. GTP is a strong inhibitor which strengthened the cooperative interactions between the ammonium binding sites. ADP as an activator relieves the inhibition by GTP. Like glutamate dehydrogenase from bovine liver, glutamate dehydrogenase from pig kidney shows the ability of self-association, too. The sedimentation coefficient increases from 13.5 S at 0.07 mg protein/ml to 19.4 S at 1.32 mg protein/ml. In the sodium dodecylsulphate gel electrophoresis the enzyme migrates as a single band with a molecular-weight at 51000.", "contents": "Purification and properties of pig kidney glutamate dehydrogenase. Glutamate dehydrogenase from pig kidney has been purified to homogeneity by means of affinity chromatography on matrix bound Cibacron Blue F3G-A and gel chromatography on Sepharose 6B. The enzyme exhibits allosteric properties with the substrates alpha-ketoglutarate, ammonium, and NADH, respectively. GTP is a strong inhibitor which strengthened the cooperative interactions between the ammonium binding sites. ADP as an activator relieves the inhibition by GTP. Like glutamate dehydrogenase from bovine liver, glutamate dehydrogenase from pig kidney shows the ability of self-association, too. The sedimentation coefficient increases from 13.5 S at 0.07 mg protein/ml to 19.4 S at 1.32 mg protein/ml. In the sodium dodecylsulphate gel electrophoresis the enzyme migrates as a single band with a molecular-weight at 51000."}
{"id": "PMID:206076", "title": "[Determination, proprerties and postnatal development of galactokinase in the swine liver].", "content": "1. Starting from the spectrophotometric method of Ballard optimal reaction conditions for measurements of galactokinase in piglet liver were systematically studied. These are (final conc. in the test): 100 mM triethanolamine-HCl buffer, 33 mM KCl, 16.5 mM NaF (inhibiting ATPase), 5 mM cysteine hydrochloride, 0.33 mM NADH2, 1 U pyruvate kinase and lactic dehydrogenase, 0.5 mM phosphoenolpyruvate, 1.5 mM galactose, 0.5 mM ATP and 1 mM MgCl2, final pH 7.5. 2. An optimal substrate concentration, a Mg: ATP-ratio of 2:1, pH-stability and addition of activators are important for the determination of galactokinase activity in the supernatant fraction of pig liver. 3. Using the optimized method galactokinase activity of pig liver in dependence on age, with particular reference to the perinatal period, was determined. 4. Galactokinase activity of liver of newborn piglets is 7 times that of adult pigs. In the suckling period the activity remains relatively constant at this high level and decreases remarkably immediately after weaning. 5. Galactokinase of liver of newborn piglets differs in kinetic properties (lower Km of ATP, higher maximal reaction velocity) from the enzyme of adult pigs, which is still insufficient to make sure the existence of two different forms of the enzyme.", "contents": "[Determination, proprerties and postnatal development of galactokinase in the swine liver]. 1. Starting from the spectrophotometric method of Ballard optimal reaction conditions for measurements of galactokinase in piglet liver were systematically studied. These are (final conc. in the test): 100 mM triethanolamine-HCl buffer, 33 mM KCl, 16.5 mM NaF (inhibiting ATPase), 5 mM cysteine hydrochloride, 0.33 mM NADH2, 1 U pyruvate kinase and lactic dehydrogenase, 0.5 mM phosphoenolpyruvate, 1.5 mM galactose, 0.5 mM ATP and 1 mM MgCl2, final pH 7.5. 2. An optimal substrate concentration, a Mg: ATP-ratio of 2:1, pH-stability and addition of activators are important for the determination of galactokinase activity in the supernatant fraction of pig liver. 3. Using the optimized method galactokinase activity of pig liver in dependence on age, with particular reference to the perinatal period, was determined. 4. Galactokinase activity of liver of newborn piglets is 7 times that of adult pigs. In the suckling period the activity remains relatively constant at this high level and decreases remarkably immediately after weaning. 5. Galactokinase of liver of newborn piglets differs in kinetic properties (lower Km of ATP, higher maximal reaction velocity) from the enzyme of adult pigs, which is still insufficient to make sure the existence of two different forms of the enzyme."}
{"id": "PMID:206077", "title": "[Repeated characterization, analysis of variance limitation and discrimination analysis classification of EEG-activity patterns in human sleep].", "content": "1. To describe quantitatively and to deliminate nine EEG sleep patterns, mean values and standard deviations of abundances of the frequencies 0.8 ... 1.8 c/sec, 2...3.5 c/sec, 4...13c/sec, 14 to 17 c/sec, 18 to 22 c/sec, and 23 to 40 c/sec as well as of the average amplitudes in selected frequency ranges were calaculated and the distributions represented. 2. All nine EEG activity patterns could be separated by means of univariate and multivariate analyses of variance on the basis of all 28 as well as the 17 indispensable variables. 3. In the course of a stepwise reduction of variables within the framework of a linear discriminant analysis an optimal set of 17 variables was determined for the separation of the patterns, comprising: the percent quantity of the frequencies 0.8 ... 3.5 c/sec, 7 ... 9 c/sec and 18 to 40 c/sec as well as the average amplitudes in the frequency ranges 0.8 to 3.5 c/sec and 7.5 to 40 c/sec. 4. By linear regression analyses it could be shown that the sleep scording system used, can be reflected on an interval scale with the aid of discriminant functions; this can be achieved on the basis of the optimal set of variables as well as of the five most indispensable variables. 5. Finally the degree of the objectivity of the scoring procedures was demonstrated. Advantages and disadvantages of sleep scoring systems were discussed and possibilities of the utilization of results suggested, also in respect to the further development of the automatic recognition of EEG activity patterns.", "contents": "[Repeated characterization, analysis of variance limitation and discrimination analysis classification of EEG-activity patterns in human sleep]. 1. To describe quantitatively and to deliminate nine EEG sleep patterns, mean values and standard deviations of abundances of the frequencies 0.8 ... 1.8 c/sec, 2...3.5 c/sec, 4...13c/sec, 14 to 17 c/sec, 18 to 22 c/sec, and 23 to 40 c/sec as well as of the average amplitudes in selected frequency ranges were calaculated and the distributions represented. 2. All nine EEG activity patterns could be separated by means of univariate and multivariate analyses of variance on the basis of all 28 as well as the 17 indispensable variables. 3. In the course of a stepwise reduction of variables within the framework of a linear discriminant analysis an optimal set of 17 variables was determined for the separation of the patterns, comprising: the percent quantity of the frequencies 0.8 ... 3.5 c/sec, 7 ... 9 c/sec and 18 to 40 c/sec as well as the average amplitudes in the frequency ranges 0.8 to 3.5 c/sec and 7.5 to 40 c/sec. 4. By linear regression analyses it could be shown that the sleep scording system used, can be reflected on an interval scale with the aid of discriminant functions; this can be achieved on the basis of the optimal set of variables as well as of the five most indispensable variables. 5. Finally the degree of the objectivity of the scoring procedures was demonstrated. Advantages and disadvantages of sleep scoring systems were discussed and possibilities of the utilization of results suggested, also in respect to the further development of the automatic recognition of EEG activity patterns."}
{"id": "PMID:206078", "title": "Ethylmorphine-N-demethylation by liver homogenate of newborn and adult rats; Enzyme kinetics and age course of Vmax and Km1.", "content": "Optimum incubation conditions for determination of ethylmorphine-N-demethylation with newborn and adult rat liver homogenate have been determined: 1 ml 1:20 liver homogenate in 1.15% KCl, 1 ml 0.1 M phosphate buffer with ethylmorphine, NADP, and glucose-6-P, final concentrations 10, 0.33 and 5 mM, respectively, no nicotinamide, no MgCl2, 1 ml 0.5 M phosphate buffer; 3 ml final volume, 20 min incubation time. With both age groups NADH increases the activity to the same extent. With NADPH, saturation could be achieved only with newborn liver, but not with adult liver homogenate. Postnatally, the activity increases about fivefold, with a break at the 10th day of life. The Lineweaver-Burk plot was linear with newborn liver homogenate, whereas for all other age groups the graphs showed an angle. Statistical analysis pointed out that a two-enzyme model fits the experimental data only insignificantly better than a one-enzyme model. From other experimental evidence and manifold reproduction without any exception of these results, however, it may be concluded that there are different monooxygenases which show different affinities towards one substrate (ethylmorphine) and which show different developmental patterns.", "contents": "Ethylmorphine-N-demethylation by liver homogenate of newborn and adult rats; Enzyme kinetics and age course of Vmax and Km1. Optimum incubation conditions for determination of ethylmorphine-N-demethylation with newborn and adult rat liver homogenate have been determined: 1 ml 1:20 liver homogenate in 1.15% KCl, 1 ml 0.1 M phosphate buffer with ethylmorphine, NADP, and glucose-6-P, final concentrations 10, 0.33 and 5 mM, respectively, no nicotinamide, no MgCl2, 1 ml 0.5 M phosphate buffer; 3 ml final volume, 20 min incubation time. With both age groups NADH increases the activity to the same extent. With NADPH, saturation could be achieved only with newborn liver, but not with adult liver homogenate. Postnatally, the activity increases about fivefold, with a break at the 10th day of life. The Lineweaver-Burk plot was linear with newborn liver homogenate, whereas for all other age groups the graphs showed an angle. Statistical analysis pointed out that a two-enzyme model fits the experimental data only insignificantly better than a one-enzyme model. From other experimental evidence and manifold reproduction without any exception of these results, however, it may be concluded that there are different monooxygenases which show different affinities towards one substrate (ethylmorphine) and which show different developmental patterns."}
{"id": "PMID:206079", "title": "[Electron transport particles from beef-heart mitochondria as a test system for inhibitors of the respiratory chain].", "content": "Respiratory inhibitors exert a potentially biocidic action on all aerobic organisms. Therefore the systematic search for them and the elucidation of their mechanism of action is of great importance. The non-phosphorylating electron transfer particles (ETP) according to Crane et al. are a suitable test object for this aim. A standardized preparation of ETP from beef heart is described and characterized enzymatically. The ETP show a variety of advantages in comparison with other systems; their field of application is broad. Owing to the absence of bypasses of the respiration, particles from animals are more suitable than those from plants for the search for fungicides and herbicides which inhibit the respiratory chain. With relatively little expense, the two standard assay systems proposed (NADH oxidase and succinate-cytochrome c oxidoreductase) pick up with certainty all inhibitors of the main pathway of the respiratory chain; they are useful for screening studies. The system proposed is also suitable for the analysis of the exact site and the mechanism of action of respiratory inhibitors. Furthermore, ETP can be used to obtain parameters of the hydrophobicity of drugs as well as for toxicological studies.", "contents": "[Electron transport particles from beef-heart mitochondria as a test system for inhibitors of the respiratory chain]. Respiratory inhibitors exert a potentially biocidic action on all aerobic organisms. Therefore the systematic search for them and the elucidation of their mechanism of action is of great importance. The non-phosphorylating electron transfer particles (ETP) according to Crane et al. are a suitable test object for this aim. A standardized preparation of ETP from beef heart is described and characterized enzymatically. The ETP show a variety of advantages in comparison with other systems; their field of application is broad. Owing to the absence of bypasses of the respiration, particles from animals are more suitable than those from plants for the search for fungicides and herbicides which inhibit the respiratory chain. With relatively little expense, the two standard assay systems proposed (NADH oxidase and succinate-cytochrome c oxidoreductase) pick up with certainty all inhibitors of the main pathway of the respiratory chain; they are useful for screening studies. The system proposed is also suitable for the analysis of the exact site and the mechanism of action of respiratory inhibitors. Furthermore, ETP can be used to obtain parameters of the hydrophobicity of drugs as well as for toxicological studies."}
{"id": "PMID:206080", "title": "Lack of correlation between adrenal cAMP and corticosteroidogenesis in the newborn rat.", "content": "In 2 to 16-day-old rats subjected to heat, the adrenal content of cAMP did not increase in animals younger than 14 days of age, but serum corticosterone was significantly higher than control values at all ages except in 10 and 12-day-old animals. This would suggest that cAMP may not mediate the adrenal steroidogenic response to stress during the first post-natal week. This hypothesis is consistent with the fact that the administration of 0.195 and 0.785 mU ACTH to 2-day-old rats resulted in a significant increase in serum corticosterone without a rise in the adrenal content of cAMP. The stress-induced rise in serum corticosterone progressively diminishes during the first post-natal week before returning to its previous 2-day-old capacity by day 16.", "contents": "Lack of correlation between adrenal cAMP and corticosteroidogenesis in the newborn rat. In 2 to 16-day-old rats subjected to heat, the adrenal content of cAMP did not increase in animals younger than 14 days of age, but serum corticosterone was significantly higher than control values at all ages except in 10 and 12-day-old animals. This would suggest that cAMP may not mediate the adrenal steroidogenic response to stress during the first post-natal week. This hypothesis is consistent with the fact that the administration of 0.195 and 0.785 mU ACTH to 2-day-old rats resulted in a significant increase in serum corticosterone without a rise in the adrenal content of cAMP. The stress-induced rise in serum corticosterone progressively diminishes during the first post-natal week before returning to its previous 2-day-old capacity by day 16."}
{"id": "PMID:206084", "title": "Inverse effects of corticosterone and thyroxine on glucocorticoid binding sites in the anterior pituitary gland.", "content": "The aim of this study was to determine whether pituitary glucocorticoid binding sites are under hormonal control. It was shown that corticosterone and thyroxine exerted antagonistic effects on both the transcortin-like component and true receptor present in the hypophysis: thyroid hormones, in contrast to glucocorticoids which exhibited opposite influence, increased maximum binding without affecting significantly the apparent association constant. Thus, it seems that the concentration of glucocorticoid binding sites is regulated by the glucocorticoid ligands, as well as by a different hormone. Moreover, a striking parallelism was found between plasma transcortin and pituitary transcotin-like capacity, argueing in favour of a plasma origin for this pituitary binder.", "contents": "Inverse effects of corticosterone and thyroxine on glucocorticoid binding sites in the anterior pituitary gland. The aim of this study was to determine whether pituitary glucocorticoid binding sites are under hormonal control. It was shown that corticosterone and thyroxine exerted antagonistic effects on both the transcortin-like component and true receptor present in the hypophysis: thyroid hormones, in contrast to glucocorticoids which exhibited opposite influence, increased maximum binding without affecting significantly the apparent association constant. Thus, it seems that the concentration of glucocorticoid binding sites is regulated by the glucocorticoid ligands, as well as by a different hormone. Moreover, a striking parallelism was found between plasma transcortin and pituitary transcotin-like capacity, argueing in favour of a plasma origin for this pituitary binder."}
{"id": "PMID:206086", "title": "Treatment of pituitary dependent Cushing's syndrome with closed stereotactic radiosurgery by means of 60Co gamma radiation.", "content": "Four patients with pituitary dependent Cushing's syndrome were treated with external irradiation to the pituitary using 60Co gamma irradiation given with a stereotactic technique. The size of the sella turcica was normal or slightly enlarged in all patients. The doses given varied between 7000 and 10 000 rad, and the observation time ranged between 14 and 20 months. Three of the patients showed complete clinical remission and one marked improvement. One patient developed ACTH insufficiency, while none developed insufficient secretion of other pituitary hormones. No complicants of the irradiation were observed.", "contents": "Treatment of pituitary dependent Cushing's syndrome with closed stereotactic radiosurgery by means of 60Co gamma radiation. Four patients with pituitary dependent Cushing's syndrome were treated with external irradiation to the pituitary using 60Co gamma irradiation given with a stereotactic technique. The size of the sella turcica was normal or slightly enlarged in all patients. The doses given varied between 7000 and 10 000 rad, and the observation time ranged between 14 and 20 months. Three of the patients showed complete clinical remission and one marked improvement. One patient developed ACTH insufficiency, while none developed insufficient secretion of other pituitary hormones. No complicants of the irradiation were observed."}
{"id": "PMID:206087", "title": "Effects of bromocriptine on the hypothalamo-pituitary axis.", "content": "The effects of bromocriptine on the secretion of prolactin, gonadotrophins, thyretrophin (TSH), corticotrophin (ACTH), somatotrophin (GH) and melanocyte-stimulating hormone (MSH) in mammals are presented and the sites and mode of action briefly discussed.", "contents": "Effects of bromocriptine on the hypothalamo-pituitary axis. The effects of bromocriptine on the secretion of prolactin, gonadotrophins, thyretrophin (TSH), corticotrophin (ACTH), somatotrophin (GH) and melanocyte-stimulating hormone (MSH) in mammals are presented and the sites and mode of action briefly discussed."}
{"id": "PMID:206090", "title": "Studies on the influence of monoamines on the cerebrovascular response to arterial hypoxia.", "content": "The cerebrovascular response to arterial hypoxia  was studied during blockade of the vascular dopamine receptors and during alpha-adrenergic receptor stimulation and blockade in anaesthetized dogs. Dopamine receptor blockade with pimozide or haloperidol invariably decreased the degree of hypoxic vasodilatation in the brain pointing to a functional role of dopamine in this situation. Alpha-receptor blockade did not change the response, while stimulation of these receptors decreased the dilatory response even in deep arterial hypoxia.", "contents": "Studies on the influence of monoamines on the cerebrovascular response to arterial hypoxia. The cerebrovascular response to arterial hypoxia  was studied during blockade of the vascular dopamine receptors and during alpha-adrenergic receptor stimulation and blockade in anaesthetized dogs. Dopamine receptor blockade with pimozide or haloperidol invariably decreased the degree of hypoxic vasodilatation in the brain pointing to a functional role of dopamine in this situation. Alpha-receptor blockade did not change the response, while stimulation of these receptors decreased the dilatory response even in deep arterial hypoxia."}
{"id": "PMID:206091", "title": "An ultrastructural study of chronic cadmium chloride-induced neuropathy.", "content": "After the long-term exposure to cadmium chloride in drinking water, the Wistar rats developed peripheral polyneuropathy. The main lesion was of myelin degeneration. Ultrastructural examination of the roots and sciatic nerves revealed segmental demyelination beginning from the node of Ranvier. There was the active autophagocytosis of Schwann cells which contained a number of myelin remnants and dense bodies. There was, on the other hand, the evidence of remyelination with toxic damage, in which the thinner myelin sheaths and abnormal myelinations were observed with increase of Schwann cells containing rich ribosomes. Axoplasmic changes were minimal, but consisted of accumulation of glycogen particles which very often produced glycogenosomes in characteristic appearance with axoplasmal dysfunction.", "contents": "An ultrastructural study of chronic cadmium chloride-induced neuropathy. After the long-term exposure to cadmium chloride in drinking water, the Wistar rats developed peripheral polyneuropathy. The main lesion was of myelin degeneration. Ultrastructural examination of the roots and sciatic nerves revealed segmental demyelination beginning from the node of Ranvier. There was the active autophagocytosis of Schwann cells which contained a number of myelin remnants and dense bodies. There was, on the other hand, the evidence of remyelination with toxic damage, in which the thinner myelin sheaths and abnormal myelinations were observed with increase of Schwann cells containing rich ribosomes. Axoplasmic changes were minimal, but consisted of accumulation of glycogen particles which very often produced glycogenosomes in characteristic appearance with axoplasmal dysfunction."}
{"id": "PMID:206092", "title": "Morphological studies of hamster brain cells transformed in vitro by a human papovavirus BK.", "content": "The cytomorphology and cytogenesis of BK virus-transformed hamster brain cells (HBBK cells) were studied. HBBK cells with indistinct processes showed a tendency to epithelial arrangement as well as characteristics of malignant tumor cells in vitro, and developed long, delicate processes when cell growth was suppressed. Glial fibrillary acidic protein was demonstrated by immunofluorescence in the cytoplasm of almost all HBBK cells. The tumors arising in hamsters after subcutaneous inoculation of HBBK cells were classified as poorly differentiated gliomas. These findings suggest that selective transformation of glial cells in hamster brain cells by BK virus occurred.", "contents": "Morphological studies of hamster brain cells transformed in vitro by a human papovavirus BK. The cytomorphology and cytogenesis of BK virus-transformed hamster brain cells (HBBK cells) were studied. HBBK cells with indistinct processes showed a tendency to epithelial arrangement as well as characteristics of malignant tumor cells in vitro, and developed long, delicate processes when cell growth was suppressed. Glial fibrillary acidic protein was demonstrated by immunofluorescence in the cytoplasm of almost all HBBK cells. The tumors arising in hamsters after subcutaneous inoculation of HBBK cells were classified as poorly differentiated gliomas. These findings suggest that selective transformation of glial cells in hamster brain cells by BK virus occurred."}
{"id": "PMID:206093", "title": "Infantile neuroaxonal dystrophy. Schwann cell inclusion in the peripheral nerve.", "content": "Abnormal Schwann cell inclusion is reported in biopsied peripheral nerve in a case of infantile neuroaxonal dystrophy. In addition to non-specific dystrophic changes of the axons, the Schwann cells contained several distinct bodies which were composed of stacks of irregularly disposed membranes; in some instances, transformed Schwann cell cytoplasm was distined with similar bodies. This change has not been reported on this condition and its significance is briefly discussed.", "contents": "Infantile neuroaxonal dystrophy. Schwann cell inclusion in the peripheral nerve. Abnormal Schwann cell inclusion is reported in biopsied peripheral nerve in a case of infantile neuroaxonal dystrophy. In addition to non-specific dystrophic changes of the axons, the Schwann cells contained several distinct bodies which were composed of stacks of irregularly disposed membranes; in some instances, transformed Schwann cell cytoplasm was distined with similar bodies. This change has not been reported on this condition and its significance is briefly discussed."}
{"id": "PMID:206094", "title": "Mixed mesenchymal and neuroectodermal tumor of the cerebellum.", "content": "An unusual cerebellar tumor composed of mixed mesenchymal and neuroectodermal elements in a 44 year old man is reported. The mesenchymal element is well-differentiated adipose tissue, whereas the neuroectodermal components exhibit a variety of medulloblastomatous, astrocytomatous, oligodendrogliomatous and ependymomatous areas. A possible origin of such unusual mixed neoplasms is briefly discussed.", "contents": "Mixed mesenchymal and neuroectodermal tumor of the cerebellum. An unusual cerebellar tumor composed of mixed mesenchymal and neuroectodermal elements in a 44 year old man is reported. The mesenchymal element is well-differentiated adipose tissue, whereas the neuroectodermal components exhibit a variety of medulloblastomatous, astrocytomatous, oligodendrogliomatous and ependymomatous areas. A possible origin of such unusual mixed neoplasms is briefly discussed."}
{"id": "PMID:206096", "title": "Effects of the antidiuretic hormone, arginine vasotocin, theophylline, filipin and A23187 on cyclic AMP in isolated frog skin epithelium (Rana temporaria).", "content": "A method for measuring cAMP in frog skin epithelium was developed. The epithelia were isolated after collagenase-treatment. cAMP was extracted by boiling water and the extract was purified on dry Al2O3. The change with time of the cAMP level after addition of arginine vasotocin (AVT) was studied. The hormone caused a rapid increase in cAMP level with a maximum after 3-5 min, whereafter the cAMP level declined. Incubation with AVT made the epithelia refractory to a second dose of AVT, which indicates that the decline in cAMP level was caused by a feedback mechanism and not by inactivation of the hormone. cAMP appeared evenly distributed in all cell-layers of the epithelia both before and after stimulation with AVT. Theophylline caused a rapid increase in the cAMP level, which remained elevated for at least 45 min. Addition of the ionophore A23187 or of filipin had no effect on the cAMP level. However, in the presence of theophylline, A23187 enhanced the cAMP level, whereas filipin had no effect. Therefore the involvement of cAMP in the action of A23187 has to be considered.", "contents": "Effects of the antidiuretic hormone, arginine vasotocin, theophylline, filipin and A23187 on cyclic AMP in isolated frog skin epithelium (Rana temporaria). A method for measuring cAMP in frog skin epithelium was developed. The epithelia were isolated after collagenase-treatment. cAMP was extracted by boiling water and the extract was purified on dry Al2O3. The change with time of the cAMP level after addition of arginine vasotocin (AVT) was studied. The hormone caused a rapid increase in cAMP level with a maximum after 3-5 min, whereafter the cAMP level declined. Incubation with AVT made the epithelia refractory to a second dose of AVT, which indicates that the decline in cAMP level was caused by a feedback mechanism and not by inactivation of the hormone. cAMP appeared evenly distributed in all cell-layers of the epithelia both before and after stimulation with AVT. Theophylline caused a rapid increase in the cAMP level, which remained elevated for at least 45 min. Addition of the ionophore A23187 or of filipin had no effect on the cAMP level. However, in the presence of theophylline, A23187 enhanced the cAMP level, whereas filipin had no effect. Therefore the involvement of cAMP in the action of A23187 has to be considered."}
{"id": "PMID:206097", "title": "Urinary cyclic AMP and vasopressin excretion in rat strains selected for their alcohol intake.", "content": "Urinary excretion of adenosine 3',5' -cyclic monophosphate (cAMP) and immunoreactive arginine vasopressin (AVP) were investigated after water loading and following ethanol loading in two rat strains selected for their voluntary ethanol intake. After ethanol loading ethanol preferring (AA) rats excreted more cAMP but less AVP than water preferring (ANA) rats. The results suggest that the strain difference in cAMP excretion is of renal origin and is not due to vasopressin or parathormone. Differences in the sympathetic nervous activity may be responsible for the difference in cAMP excretion.", "contents": "Urinary cyclic AMP and vasopressin excretion in rat strains selected for their alcohol intake. Urinary excretion of adenosine 3',5' -cyclic monophosphate (cAMP) and immunoreactive arginine vasopressin (AVP) were investigated after water loading and following ethanol loading in two rat strains selected for their voluntary ethanol intake. After ethanol loading ethanol preferring (AA) rats excreted more cAMP but less AVP than water preferring (ANA) rats. The results suggest that the strain difference in cAMP excretion is of renal origin and is not due to vasopressin or parathormone. Differences in the sympathetic nervous activity may be responsible for the difference in cAMP excretion."}
{"id": "PMID:206099", "title": "Lymphatic dissemination of bone and soft tissue sarcomas: a lymphographic investigation.", "content": "The series consisted of 132 patients, 61 with primary bone sarcomas and 71 with primary soft tissue sarcomas. The patients were all evaluated by lymphography. The investigation included both patients who had not yet been treated and patients with suspected or confirmed metastases. All tumour diagnoses were confirmed microscopically. The findings as regards dissemination were based on clinical examinations, laboratory tests, roentgen examinations and lymphographies. In some cases, lymph node biopsies and surgical observations were also used. A total of 151 lymphographies were performed and 281 follow-up films taken. Preoperative lymphography was performed using the technique introduced by Kinmonth. For postoperative lymphography on the stumps of amputated extremities, two simple but useful methods were developed, which are presented here. Changes in the lymphographic appearance of lymph node metastases, the occurrence of new metastases, and the results of treatment were assessed by survey films and repeat lymphography. The generally accepted criteria for metastasis were used as a basis for the analysis of the lymphographic findings. The results may be summarized as follows: 1. Incidence of lymphatic dissemination. Different sarcomas varied greatly in their clinical course, including the frequency of dissemination. The lymphatic involvement in the metastatic cases was as follows: Bone sarcomas: 16 out of 28 (Table 10); of these, 13 were to regional lymph nodes, 8 to distant nodes and 5 to both (Table 14). Soft tissue sarcomas: 24 out of 40 (Table 11). All 24 had metastases in regional nodes, and 8 in distant nodes as well (Table 15). The highest frequencies of lymphatic spread in the different metastasized tumours were found to be: Bone sarcomas: reticulosarcoma 100%, Ewing's sarcoma 50%, osteosarcoma 47%. Soft tissue sarcomas: rhabdomyosarcoma 100%, synovial sarcoma 80%, neurogenic sarcoma 78%, leiomyosarcoma 67%. 2. Time-relation between lymphatic and haematogenic dissemination; The tendency to metastasize first via the lymphatics or via the blood vessels varied. Half of the cases of Ewing's sarcoma and reticulosarcoma had evidence of lymphatic spread before blood-borne metastases were detected. In the osteosarcoma cases, however, lymphatic dissemination was always preceded by haematogenic spread (Table 12). In synovial sarcoma, rhabdomyosarcoma and neurogenic sarcoma, the first dissemination was more frequently lymphatic than haematogenic (Table 13). 3. Possible existence of special lymphographic features of sarcoma metastases. Only reticulosarcoma displayed special characteristics. The lymph node metastases of reticulosarcoma of bone had lymphographic appearances similar to those found in reticulosarcoma of soft tissue or lymph node origin (Fig. 12). The lymph node metastases of other primary bone and soft tissue sarcomas had no specific lymphographic features and were indistinguishable from carcinomatous metastases (Figs 7, 9, 13, 15, 18, 19, 20, 22, 23). 4...", "contents": "Lymphatic dissemination of bone and soft tissue sarcomas: a lymphographic investigation. The series consisted of 132 patients, 61 with primary bone sarcomas and 71 with primary soft tissue sarcomas. The patients were all evaluated by lymphography. The investigation included both patients who had not yet been treated and patients with suspected or confirmed metastases. All tumour diagnoses were confirmed microscopically. The findings as regards dissemination were based on clinical examinations, laboratory tests, roentgen examinations and lymphographies. In some cases, lymph node biopsies and surgical observations were also used. A total of 151 lymphographies were performed and 281 follow-up films taken. Preoperative lymphography was performed using the technique introduced by Kinmonth. For postoperative lymphography on the stumps of amputated extremities, two simple but useful methods were developed, which are presented here. Changes in the lymphographic appearance of lymph node metastases, the occurrence of new metastases, and the results of treatment were assessed by survey films and repeat lymphography. The generally accepted criteria for metastasis were used as a basis for the analysis of the lymphographic findings. The results may be summarized as follows: 1. Incidence of lymphatic dissemination. Different sarcomas varied greatly in their clinical course, including the frequency of dissemination. The lymphatic involvement in the metastatic cases was as follows: Bone sarcomas: 16 out of 28 (Table 10); of these, 13 were to regional lymph nodes, 8 to distant nodes and 5 to both (Table 14). Soft tissue sarcomas: 24 out of 40 (Table 11). All 24 had metastases in regional nodes, and 8 in distant nodes as well (Table 15). The highest frequencies of lymphatic spread in the different metastasized tumours were found to be: Bone sarcomas: reticulosarcoma 100%, Ewing's sarcoma 50%, osteosarcoma 47%. Soft tissue sarcomas: rhabdomyosarcoma 100%, synovial sarcoma 80%, neurogenic sarcoma 78%, leiomyosarcoma 67%. 2. Time-relation between lymphatic and haematogenic dissemination; The tendency to metastasize first via the lymphatics or via the blood vessels varied. Half of the cases of Ewing's sarcoma and reticulosarcoma had evidence of lymphatic spread before blood-borne metastases were detected. In the osteosarcoma cases, however, lymphatic dissemination was always preceded by haematogenic spread (Table 12). In synovial sarcoma, rhabdomyosarcoma and neurogenic sarcoma, the first dissemination was more frequently lymphatic than haematogenic (Table 13). 3. Possible existence of special lymphographic features of sarcoma metastases. Only reticulosarcoma displayed special characteristics. The lymph node metastases of reticulosarcoma of bone had lymphographic appearances similar to those found in reticulosarcoma of soft tissue or lymph node origin (Fig. 12). The lymph node metastases of other primary bone and soft tissue sarcomas had no specific lymphographic features and were indistinguishable from carcinomatous metastases (Figs 7, 9, 13, 15, 18, 19, 20, 22, 23). 4..."}
{"id": "PMID:206105", "title": "Cytomegalovirus pneumonia after treatment with melphalan and prednisone. Report of a case.", "content": "A patient with multiple myeloma had pancytopenia after treatment with melphalan and prednisone and died of an interstitial pneumonia. Post-mortem examinations showed cytomegalic cells in the lungs. Lung tissue showed a high titer of cytomegalovirus. Only when other causes have been ruled out by microbiologic, serologic, and histologic examinations should melphalan be believed to cause respiratory illness.", "contents": "Cytomegalovirus pneumonia after treatment with melphalan and prednisone. Report of a case. A patient with multiple myeloma had pancytopenia after treatment with melphalan and prednisone and died of an interstitial pneumonia. Post-mortem examinations showed cytomegalic cells in the lungs. Lung tissue showed a high titer of cytomegalovirus. Only when other causes have been ruled out by microbiologic, serologic, and histologic examinations should melphalan be believed to cause respiratory illness."}
{"id": "PMID:206122", "title": "Effect of prostaglandins and some methyl derivatives on the ductus arteriosus.", "content": "In vitro studies showed that PGF2a constricted the ductus arteriosus of newborn animals, whereas PGEs produced dilatation. The finding that constriction could also be produced by c-GMP and dilatation by c-AMP raised the possibility that the PGs might produce their effects by altering the relative proportions of cyclic nucleotides in the ductus wall. Results of experiments with inhibitors of PG synthesis and with drugs which are known to interfere with the degradation of c-GMP and c-AMP accorded with this hypothesis. Angiographic studies in neonatal piglets showed that PGEs and PGAs were potent dilators of the ductus. Prostaglandin action was confirmed in infants with congenital heart disease who were dependent on ductus patency for survival. In those patients, PGs proved to be an extremely useful tool. Experimental studies are in progress in the hope of finding a PGE analog, active by the oral route, which may be suitable for the long-term treatment of patients.", "contents": "Effect of prostaglandins and some methyl derivatives on the ductus arteriosus. In vitro studies showed that PGF2a constricted the ductus arteriosus of newborn animals, whereas PGEs produced dilatation. The finding that constriction could also be produced by c-GMP and dilatation by c-AMP raised the possibility that the PGs might produce their effects by altering the relative proportions of cyclic nucleotides in the ductus wall. Results of experiments with inhibitors of PG synthesis and with drugs which are known to interfere with the degradation of c-GMP and c-AMP accorded with this hypothesis. Angiographic studies in neonatal piglets showed that PGEs and PGAs were potent dilators of the ductus. Prostaglandin action was confirmed in infants with congenital heart disease who were dependent on ductus patency for survival. In those patients, PGs proved to be an extremely useful tool. Experimental studies are in progress in the hope of finding a PGE analog, active by the oral route, which may be suitable for the long-term treatment of patients."}
{"id": "PMID:206123", "title": "Bronchioloalveolar carcinoma: two clinical entities with one pathologic diagnosis.", "content": "Bronchioloalveolar carcinoma may present with a variety of radiologic and clinical patterns. Two types of this primary carcinoma of the lung have been recognized: a solitary lesion and a diffuse form. Charts and radiographs of 61 cases of bronchioloalveolar carcinoma were reviewed as well as the pertinent literature. Our experience indicates that the localized form seldom, if ever, becomes diffuse and has a good prognosis following appropriate surgery (lobectomy or pneumonectomy). If the lesion is diffuse, death almost invariably results within 3 years. Based on available clinical information, we suggest that at least two primary tumors of the lung have the histologic pattern of bronchioloalveolar carcinoma: one of these tumors is diffuse and the other is solitary.", "contents": "Bronchioloalveolar carcinoma: two clinical entities with one pathologic diagnosis. Bronchioloalveolar carcinoma may present with a variety of radiologic and clinical patterns. Two types of this primary carcinoma of the lung have been recognized: a solitary lesion and a diffuse form. Charts and radiographs of 61 cases of bronchioloalveolar carcinoma were reviewed as well as the pertinent literature. Our experience indicates that the localized form seldom, if ever, becomes diffuse and has a good prognosis following appropriate surgery (lobectomy or pneumonectomy). If the lesion is diffuse, death almost invariably results within 3 years. Based on available clinical information, we suggest that at least two primary tumors of the lung have the histologic pattern of bronchioloalveolar carcinoma: one of these tumors is diffuse and the other is solitary."}
{"id": "PMID:206124", "title": "Opportunistic ocular infections.", "content": "Since corticosteroids were introduced, a steadily increasing number of opportunistic pathogens have been causing major disease in both systemically and locally compromised hosts. In ocular disease, the most common cause of compromise (and of infection with such opportunistic pathogens as the herpeviruses, many gram-negative bacteria, numerous fungi and Toxoplasma) is the topical use of corticosteroids and antibiotic-corticosteroid preparations. To avoid the damaging and sometimes blinding results of opportunistic infection, the use of these preparations should be carefully restricted.", "contents": "Opportunistic ocular infections. Since corticosteroids were introduced, a steadily increasing number of opportunistic pathogens have been causing major disease in both systemically and locally compromised hosts. In ocular disease, the most common cause of compromise (and of infection with such opportunistic pathogens as the herpeviruses, many gram-negative bacteria, numerous fungi and Toxoplasma) is the topical use of corticosteroids and antibiotic-corticosteroid preparations. To avoid the damaging and sometimes blinding results of opportunistic infection, the use of these preparations should be carefully restricted."}
{"id": "PMID:206125", "title": "Silica flour exposures in Ontario.", "content": "A total of 16 cases of silicosis are reported in Ontario plants where there was exposure to silica flour. Dust counts expressed as mppcf are shown for four of these plants taken over a period of 37 years. A relationship has been obtained experimentally to permit conversion of the counts to respirable mass concentrations. Based on the information obtained, a TLV of 0.05 mg/m3 for silica flour is proposed.", "contents": "Silica flour exposures in Ontario. A total of 16 cases of silicosis are reported in Ontario plants where there was exposure to silica flour. Dust counts expressed as mppcf are shown for four of these plants taken over a period of 37 years. A relationship has been obtained experimentally to permit conversion of the counts to respirable mass concentrations. Based on the information obtained, a TLV of 0.05 mg/m3 for silica flour is proposed."}
{"id": "PMID:206127", "title": "Vitamin B6 nutritional status of pellagrins and their leucine tolerance.", "content": "Disturbances in tryptophan-nicotinamide adenine dinucleotide pathway, seen in pellagrins whose staple is sorghum have been ascribed to an amino acid imbalance caused by excess intake of leucine. Studies in normal human volunteers and in experimental animals have shown that administration of vitamin B6 will counteract some of the metabolic effects of leucine. In view of these observations, two clinical studies were conducted--one to investigate the vitamin B6 nutritional status of pellagrins and the other to determine whether plasma leucine clearance in pellagrins is different from that of normals. Vitamin B6 nutritional status of pellagrins was found to be far from satisfactory, as indicated by elevated levels of xanthurenic acid and kynurenic acid in urine after a tryptophan load and low plasma pyridoxal phosphate levels. Plasma leucine concentrations at 1, 2, and 4 hr after a leucine load were significantly higher in pellagrins than those in normals. Administration of 25 mg of vitamin B6, intramuscularly 30 min before leucine load significantly decreased plasma leucine concentration in pellagrins. However, the leucine concentration at 4th hr did not return to basal level. Administration of vitamin B6 10 TO 20 mg/day orally for 10 to 15 days normalized leucine tolerance in pellagrins. Data presented here suggest that when the diets contain excess leucine, additional amounts of vitamin B6 are required.", "contents": "Vitamin B6 nutritional status of pellagrins and their leucine tolerance. Disturbances in tryptophan-nicotinamide adenine dinucleotide pathway, seen in pellagrins whose staple is sorghum have been ascribed to an amino acid imbalance caused by excess intake of leucine. Studies in normal human volunteers and in experimental animals have shown that administration of vitamin B6 will counteract some of the metabolic effects of leucine. In view of these observations, two clinical studies were conducted--one to investigate the vitamin B6 nutritional status of pellagrins and the other to determine whether plasma leucine clearance in pellagrins is different from that of normals. Vitamin B6 nutritional status of pellagrins was found to be far from satisfactory, as indicated by elevated levels of xanthurenic acid and kynurenic acid in urine after a tryptophan load and low plasma pyridoxal phosphate levels. Plasma leucine concentrations at 1, 2, and 4 hr after a leucine load were significantly higher in pellagrins than those in normals. Administration of 25 mg of vitamin B6, intramuscularly 30 min before leucine load significantly decreased plasma leucine concentration in pellagrins. However, the leucine concentration at 4th hr did not return to basal level. Administration of vitamin B6 10 TO 20 mg/day orally for 10 to 15 days normalized leucine tolerance in pellagrins. Data presented here suggest that when the diets contain excess leucine, additional amounts of vitamin B6 are required."}
{"id": "PMID:206129", "title": "Marked elevation of serum angiotension-converting enzyme and hepatic fibrosis containing long-spacing collagen fibrils in type 2 acute neuronopathic Gaucher's disease.", "content": "Serum angiotensin-converting enzyme in a patient with type 2 acute neuronopathic Gaucher's disease (242 nmol/min/ml) was 10.8 times higher than values for eight patients with other hereditary neurologic abnormalities (22.5 +/- 2.0) and 9.4 times higher than those for 12 patients with other diseases (25.7 +/- 2.6) (P less than 0.001). Serum lysozyme was not elevated in the patient with type 2 Gaucher's disease. These results indicate that elevated serum angiotensin-converting enzyme in an infant with neurologic involvement and hepatosplenomegaly is suggestive of the possibility of type 2 Gaucher's disease. Typical Gaucher's cells and fibrosis were observed by light and electron microscopy of the liver. An aspect hitherto unreported in Gaucher's disease or in the liver was that approximately 20% of the collagen fibrils were of the long-spacing type, with periodicity of 1,000 to 1,100 A and diameters of 900 to 1,500 A.", "contents": "Marked elevation of serum angiotension-converting enzyme and hepatic fibrosis containing long-spacing collagen fibrils in type 2 acute neuronopathic Gaucher's disease. Serum angiotensin-converting enzyme in a patient with type 2 acute neuronopathic Gaucher's disease (242 nmol/min/ml) was 10.8 times higher than values for eight patients with other hereditary neurologic abnormalities (22.5 +/- 2.0) and 9.4 times higher than those for 12 patients with other diseases (25.7 +/- 2.6) (P less than 0.001). Serum lysozyme was not elevated in the patient with type 2 Gaucher's disease. These results indicate that elevated serum angiotensin-converting enzyme in an infant with neurologic involvement and hepatosplenomegaly is suggestive of the possibility of type 2 Gaucher's disease. Typical Gaucher's cells and fibrosis were observed by light and electron microscopy of the liver. An aspect hitherto unreported in Gaucher's disease or in the liver was that approximately 20% of the collagen fibrils were of the long-spacing type, with periodicity of 1,000 to 1,100 A and diameters of 900 to 1,500 A."}
{"id": "PMID:206132", "title": "Fatal rotavirus gastroenteritis: an analysis of 21 cases.", "content": "During the period of May 1972 to March 1977, twenty-one fatal cases of rotavirus acute gastroenteritis were recorded in the city of Toronto. The mean age of these subjects was approximately 1 year. Boys outnumbered girls by 12 to 9. Death occurred within three days of onset of symptoms in all cases. Sixteen of the subjects were profoundly dehydrated and had sodium levels (serum or vitreous humor) in excess of 150 mEq/liter. In 11 subjects, sodium values were greater than 160 mEq/liter. Although a physician was contacted in 16 instances, these infants still perished. We suggest that both language difficulties and the rapid rate of fluid depletion contributed significantly to the fatal outcome. At autopsy the bowel was often dilated and filled with fluid. Postmortem autolysis precluded an accurate histological assessment of the small bowel mucosa.", "contents": "Fatal rotavirus gastroenteritis: an analysis of 21 cases. During the period of May 1972 to March 1977, twenty-one fatal cases of rotavirus acute gastroenteritis were recorded in the city of Toronto. The mean age of these subjects was approximately 1 year. Boys outnumbered girls by 12 to 9. Death occurred within three days of onset of symptoms in all cases. Sixteen of the subjects were profoundly dehydrated and had sodium levels (serum or vitreous humor) in excess of 150 mEq/liter. In 11 subjects, sodium values were greater than 160 mEq/liter. Although a physician was contacted in 16 instances, these infants still perished. We suggest that both language difficulties and the rapid rate of fluid depletion contributed significantly to the fatal outcome. At autopsy the bowel was often dilated and filled with fluid. Postmortem autolysis precluded an accurate histological assessment of the small bowel mucosa."}
{"id": "PMID:206133", "title": "Massive upper gastrointestinal hemorrhage from a granular cell tumor of the stomach.", "content": "The first case of massive upper gastrointestinal hemorrhaging from a granular cell tumor of the stomach is reported. The clinical and pathologic characteristics of the 15 previously reported cases are reviewed and the theories of the histogenesis of this lesion are briefly discussed.", "contents": "Massive upper gastrointestinal hemorrhage from a granular cell tumor of the stomach. The first case of massive upper gastrointestinal hemorrhaging from a granular cell tumor of the stomach is reported. The clinical and pathologic characteristics of the 15 previously reported cases are reviewed and the theories of the histogenesis of this lesion are briefly discussed."}
{"id": "PMID:206134", "title": "Antigenic relatedness of 17 strains of human cytomegalovirus.", "content": "A 10 minute kinetic neutralization test was used to assess antigenic relatedness among 17 strains of human cytomegalovirus. Hyperimmune guinea pig sera exhibited extensive cross-reactivity. However, the data did suggest that there may be four antigenic groups represented in this collection of CMV strains. Available epidemiologic data for these strains do not provide any discernible basis for this grouping.", "contents": "Antigenic relatedness of 17 strains of human cytomegalovirus. A 10 minute kinetic neutralization test was used to assess antigenic relatedness among 17 strains of human cytomegalovirus. Hyperimmune guinea pig sera exhibited extensive cross-reactivity. However, the data did suggest that there may be four antigenic groups represented in this collection of CMV strains. Available epidemiologic data for these strains do not provide any discernible basis for this grouping."}
{"id": "PMID:206138", "title": "Hypercalcemia with suppressed parathyroid hormone in Burkitt's lymphoma.", "content": "Two patients with Burkitt's lymphoma presented with severe hypercalcemia, a previously unreported complication of this tumor. Roentgenograms and radionuclide scans showed multiple osteolytic lesions in both patients. Plasma parathyroid hormone (PTH) was undetectable during the hypercalcemia phase. Chemotherapy was followed by rapid tumor lysis, hyperphosphatemia, phosphaturia and hypocalcemia. The hypocalcemic phase persisted for two weeks despite rapid normalization of serum phosphorus and renal function. Measurement of urinary cyclic AMP, an index of PTH action, indicated that parathyroid function had been suppressed by the hypercalcemia and remained suppressed for almost one week despite marked hypocalcemia.", "contents": "Hypercalcemia with suppressed parathyroid hormone in Burkitt's lymphoma. Two patients with Burkitt's lymphoma presented with severe hypercalcemia, a previously unreported complication of this tumor. Roentgenograms and radionuclide scans showed multiple osteolytic lesions in both patients. Plasma parathyroid hormone (PTH) was undetectable during the hypercalcemia phase. Chemotherapy was followed by rapid tumor lysis, hyperphosphatemia, phosphaturia and hypocalcemia. The hypocalcemic phase persisted for two weeks despite rapid normalization of serum phosphorus and renal function. Measurement of urinary cyclic AMP, an index of PTH action, indicated that parathyroid function had been suppressed by the hypercalcemia and remained suppressed for almost one week despite marked hypocalcemia."}
{"id": "PMID:206139", "title": "Combined deficiency of glucose-6-phosphatase and fructose-1, 6-diphosphatase. Studies of glucagon secretion and fuel utilization.", "content": "An adult woman with hypoglycemia, hyperlactatemia, hyperuricemia, hypertriglyceridemia, hyperketonemia and inability to make new glucose from galactose, fructose, glycerol and alanine was found to have no hepatic glucose-6-phosphatase and deficient fructose-1,6-diphosphatase. Nonautonomous hyperglucagonemia was demonstrated and shown to contribute to the hyperlactatemia and hyperketonemia. A paradoxic hyperlactatemic response to glucose and galactose was observed. Studies of substrate utilization showed prompt adaptation to changes in dietary supply of energy which probably accounted for her never having experienced symptoms of hypoglycemia.", "contents": "Combined deficiency of glucose-6-phosphatase and fructose-1, 6-diphosphatase. Studies of glucagon secretion and fuel utilization. An adult woman with hypoglycemia, hyperlactatemia, hyperuricemia, hypertriglyceridemia, hyperketonemia and inability to make new glucose from galactose, fructose, glycerol and alanine was found to have no hepatic glucose-6-phosphatase and deficient fructose-1,6-diphosphatase. Nonautonomous hyperglucagonemia was demonstrated and shown to contribute to the hyperlactatemia and hyperketonemia. A paradoxic hyperlactatemic response to glucose and galactose was observed. Studies of substrate utilization showed prompt adaptation to changes in dietary supply of energy which probably accounted for her never having experienced symptoms of hypoglycemia."}
{"id": "PMID:206136", "title": "The swine flu immunization program: scientific venture or political folly?", "content": "The author of this Article, an internationally recognized coroner perhaps best known among laymen for his incisive and tenacious criticism of the Warren Commission report on the Kennedy assassination, turns his attention to the federal government's 1976--1977 Swine Flu Immunization Program. Dr. Wecht contends that although this program may have been viewed by its key proponents as having great public health importance, or perhaps even political value, its creation and continuation nevertheless were scientifically unjustified. Furthermore, he contends, the federal government failed to inform the public adequately of important facts about the program's origins and progress, and it mismanaged the program in several important respects. Among the topics he discusses are swine flu's epidemiological history (including the 1976 Fort Dix outbreak that propelled swine flu into the national consciousness); the key elements leading to the government's decision to immunize; the government's failure to reevaluate the program seriously as problems arose; the shortcomings of the federal swine flu statute; the inadequacy of the government's investigation of the deaths of three persons in Pittsburgh within a few hours after being vaccinated (a matter that was of immediate concern to the author in his role as Coroner of Allegheny County, Pennsylvania); the long-delayed termination of the program following the emergence of a possible statistical link between the immunizations and an increase in the incidence of the Guillain-Barr\u00e9 Syndrome; the financial and human costs of the program; and the need for calmer, more objective decision making in future situations where immunization of the general populace is being considered.", "contents": "The swine flu immunization program: scientific venture or political folly? The author of this Article, an internationally recognized coroner perhaps best known among laymen for his incisive and tenacious criticism of the Warren Commission report on the Kennedy assassination, turns his attention to the federal government's 1976--1977 Swine Flu Immunization Program. Dr. Wecht contends that although this program may have been viewed by its key proponents as having great public health importance, or perhaps even political value, its creation and continuation nevertheless were scientifically unjustified. Furthermore, he contends, the federal government failed to inform the public adequately of important facts about the program's origins and progress, and it mismanaged the program in several important respects. Among the topics he discusses are swine flu's epidemiological history (including the 1976 Fort Dix outbreak that propelled swine flu into the national consciousness); the key elements leading to the government's decision to immunize; the government's failure to reevaluate the program seriously as problems arose; the shortcomings of the federal swine flu statute; the inadequacy of the government's investigation of the deaths of three persons in Pittsburgh within a few hours after being vaccinated (a matter that was of immediate concern to the author in his role as Coroner of Allegheny County, Pennsylvania); the long-delayed termination of the program following the emergence of a possible statistical link between the immunizations and an increase in the incidence of the Guillain-Barr\u00e9 Syndrome; the financial and human costs of the program; and the need for calmer, more objective decision making in future situations where immunization of the general populace is being considered."}
{"id": "PMID:206141", "title": "Elevated levels of cerebrospinal fluid guanosine 3',5'-cyclic monophosphate (C-GMP) in systemic lupus erythematosus.", "content": "Cerebrospinal fluid samples from patients with systemic lupus erythematosus (SLE) and neurologic involvement were evaluated for guanosine 3',5'-cyclic monophosphate (C-GMP) and cyclic adenosine monophosphate (C-GMP) content by radioimmunoassay and radioassay, respectively. Twenty-five samples from 15 patients with SLE had an average C-GMP level of 2.4 nM +/- 0.44 (average +/- SE) compared with 0.68 nM +/- 0.14 in a control group with lumbosacral pain (p less than 0.0002). No significant difference was noted in C-AMP content between patients with SLE and control subjects. C-GMP levels in cerebrospinal fluid samples from patients with SLE who had changing neurologic disease were higher than in those with stable neurologic disease. Elevated C-GMP levels in cerebrospinal fluid correlated with the leukocyte number in cerebrospinal fluid (r = 0.53 p less than 0.01), but not with the initial pressure, protein concentration or daily prednisone dosage. Experimental results suggested that leukocytes in the cerebrospinal fluid were not the source of elevated C-GMP levels. Thus, elevated C-GMP levels in cerebrospinal fluid of patients with SLE appeared to reflect neurologic involvement. C-GMP levels were alos found to be elevated in five patients with other active neurologic diseases; thus, measurement of C-GMP in cerebrospinal fluid may have more general diagnostic value.", "contents": "Elevated levels of cerebrospinal fluid guanosine 3',5'-cyclic monophosphate (C-GMP) in systemic lupus erythematosus. Cerebrospinal fluid samples from patients with systemic lupus erythematosus (SLE) and neurologic involvement were evaluated for guanosine 3',5'-cyclic monophosphate (C-GMP) and cyclic adenosine monophosphate (C-GMP) content by radioimmunoassay and radioassay, respectively. Twenty-five samples from 15 patients with SLE had an average C-GMP level of 2.4 nM +/- 0.44 (average +/- SE) compared with 0.68 nM +/- 0.14 in a control group with lumbosacral pain (p less than 0.0002). No significant difference was noted in C-AMP content between patients with SLE and control subjects. C-GMP levels in cerebrospinal fluid samples from patients with SLE who had changing neurologic disease were higher than in those with stable neurologic disease. Elevated C-GMP levels in cerebrospinal fluid correlated with the leukocyte number in cerebrospinal fluid (r = 0.53 p less than 0.01), but not with the initial pressure, protein concentration or daily prednisone dosage. Experimental results suggested that leukocytes in the cerebrospinal fluid were not the source of elevated C-GMP levels. Thus, elevated C-GMP levels in cerebrospinal fluid of patients with SLE appeared to reflect neurologic involvement. C-GMP levels were alos found to be elevated in five patients with other active neurologic diseases; thus, measurement of C-GMP in cerebrospinal fluid may have more general diagnostic value."}
{"id": "PMID:206142", "title": "Cure of acromegaly by operative removal of an islet cell tumor of the pancreas.", "content": "We studied a 30 year old woman in whom acromegaly was cured by operative removal of a large cystic beta cell adenoma of the pancreas. We detected substantial amounts of immunoreactive human growth hormone (hGH)-like activity in a tumor tissue extract. Extracts of the tumor and a normal human pituitary gland eluted from a Sephadex G-75 column in two identical peaks. Serial dilutions of the tumor extract displaced radioactive 125I hGH parallel to a standard curve. Surprisingly, an extract of a normal human pancreas contained large amounts of hGH-like activity and gave results similar to those of the tumor extract on gel chromatography and on serial dilution displacement in the growth hormone immunoassay. Paper electrophoretic studies of 125I hGH after incubation with normal pancreatic and tumor extracts with and without enzyme inhibitors suggested that pancreatic proteolytic enzymes damaged the 125I hGH used in growth hormone radioimmunoassay and produced a false detection of hGH.", "contents": "Cure of acromegaly by operative removal of an islet cell tumor of the pancreas. We studied a 30 year old woman in whom acromegaly was cured by operative removal of a large cystic beta cell adenoma of the pancreas. We detected substantial amounts of immunoreactive human growth hormone (hGH)-like activity in a tumor tissue extract. Extracts of the tumor and a normal human pituitary gland eluted from a Sephadex G-75 column in two identical peaks. Serial dilutions of the tumor extract displaced radioactive 125I hGH parallel to a standard curve. Surprisingly, an extract of a normal human pancreas contained large amounts of hGH-like activity and gave results similar to those of the tumor extract on gel chromatography and on serial dilution displacement in the growth hormone immunoassay. Paper electrophoretic studies of 125I hGH after incubation with normal pancreatic and tumor extracts with and without enzyme inhibitors suggested that pancreatic proteolytic enzymes damaged the 125I hGH used in growth hormone radioimmunoassay and produced a false detection of hGH."}
{"id": "PMID:206143", "title": "Platelet microtubules and giant granules in the Chediak-Higashi syndrome.", "content": "Platelets from a child with the characteristic clinical and laboratory features of the Chediak-Higashi Syndrome (CHS) were evaluated in the electron microscope. Rare peripheral blood platelets were found to contain the giant abnormal granules observed previously in nearly all leukocytes. The discoid CHS platelets contained circumferential bundles of microtubules identical to those present in normal cells. CHS platelet microtubules responded in the same manner as those in normal cells when patient platelets were exposed to collagen, cold, or to chilling and rewarming. The findings are inconsistent with the concept that a defect in microtubule assembly is the fundamental abnormality responsible for aberrent function of CHS cells.", "contents": "Platelet microtubules and giant granules in the Chediak-Higashi syndrome. Platelets from a child with the characteristic clinical and laboratory features of the Chediak-Higashi Syndrome (CHS) were evaluated in the electron microscope. Rare peripheral blood platelets were found to contain the giant abnormal granules observed previously in nearly all leukocytes. The discoid CHS platelets contained circumferential bundles of microtubules identical to those present in normal cells. CHS platelet microtubules responded in the same manner as those in normal cells when patient platelets were exposed to collagen, cold, or to chilling and rewarming. The findings are inconsistent with the concept that a defect in microtubule assembly is the fundamental abnormality responsible for aberrent function of CHS cells."}
{"id": "PMID:206144", "title": "Effect of estrogen treatment for one year on carbohydrate and lipid metabolism in women with normal and abnormal glucose tolerance test results. Glucose, insulin, growth hormone, triglycerides, and Premarin.", "content": "A prospective study of the effects of a conjugated estrogen (Premarin, 1.25 mg.) was performed in 36 women over a 1 year period. Each subject received a 3 hour oral glucose tolerance test before starting the medication and another after 1 year of use. The blood glucose levels were similar at five times during the two tests except for a significant elevation of the 1 hour value at the 1 year test. There were no changes in the plasma insulin, growth hormone, or fasting triglyceride levels. These results suggest that the cyclic administration of this estrogen does not alter lipid or carbohydrate metabolism.", "contents": "Effect of estrogen treatment for one year on carbohydrate and lipid metabolism in women with normal and abnormal glucose tolerance test results. Glucose, insulin, growth hormone, triglycerides, and Premarin. A prospective study of the effects of a conjugated estrogen (Premarin, 1.25 mg.) was performed in 36 women over a 1 year period. Each subject received a 3 hour oral glucose tolerance test before starting the medication and another after 1 year of use. The blood glucose levels were similar at five times during the two tests except for a significant elevation of the 1 hour value at the 1 year test. There were no changes in the plasma insulin, growth hormone, or fasting triglyceride levels. These results suggest that the cyclic administration of this estrogen does not alter lipid or carbohydrate metabolism."}
{"id": "PMID:206146", "title": "Abortive and productive infections of human mononuclear phagocytes by type I herpes simplex virus.", "content": "The ability of Type I herpes simplex (HSV) to replicate in normal human monouclear phagocytes was investigated. Mononuclear leukocytes were obtained from the peripheral blood of patients by Ficoll-Hypaque gradient centrifugation, and the monocytes were isolated by allowing the cells to adhere to tissue culture dishes. The monocytes (10(5.0) cells) were infected (10(7.0) PFU HSV) either immediately after isolation or were cultured in vitro for varying numbers of days and were then infected. Inoculation of freshly isolated monocytes resulted primarily in an abortive infection. HSV antigens were produced by the cells, as determined by a indirect fluorescent antibody technique, and empty herpes capsid structures were detected by electron microscopy of the inoculated monocytes; however, no increase in virus titer was noted in the cultures. Inoculation of viable cells that had been maintained for 7 days in culture resulted in a productive infection. An increase in titer was noted 24 hours after inoculation, and normal virus maturation was documented by ultrastructural study of the infected cells. The experiments show that the interaction of HSV with human mononuclear phagocytes is complex, and the data suggest that whether or not the cell replicates infectious virus may depend on the functional activity of the cell.", "contents": "Abortive and productive infections of human mononuclear phagocytes by type I herpes simplex virus. The ability of Type I herpes simplex (HSV) to replicate in normal human monouclear phagocytes was investigated. Mononuclear leukocytes were obtained from the peripheral blood of patients by Ficoll-Hypaque gradient centrifugation, and the monocytes were isolated by allowing the cells to adhere to tissue culture dishes. The monocytes (10(5.0) cells) were infected (10(7.0) PFU HSV) either immediately after isolation or were cultured in vitro for varying numbers of days and were then infected. Inoculation of freshly isolated monocytes resulted primarily in an abortive infection. HSV antigens were produced by the cells, as determined by a indirect fluorescent antibody technique, and empty herpes capsid structures were detected by electron microscopy of the inoculated monocytes; however, no increase in virus titer was noted in the cultures. Inoculation of viable cells that had been maintained for 7 days in culture resulted in a productive infection. An increase in titer was noted 24 hours after inoculation, and normal virus maturation was documented by ultrastructural study of the infected cells. The experiments show that the interaction of HSV with human mononuclear phagocytes is complex, and the data suggest that whether or not the cell replicates infectious virus may depend on the functional activity of the cell."}
{"id": "PMID:206147", "title": "Simian adenoviral pneumonia.", "content": "In the past 6 years we have encountered 26 cases of fatal adenoviral pneumonia in six species of simian primates. O these, 22 animals were between 11 and 38 days old at the time of death, and pneumonia was the primary clinical disease. The spectrum of clinical disease varied from peracute fatal disease to inapparent disease with seroconversion. In one outbreak involving 4 infants housed together in an isolation unit, simian virus 11 was isolated from 3 of the infants and seroconversion occurred in all 4. At necropsy the lungs were voluminous, with firm gray areas of consolidation. On histopathologic examination, severe patchy necrotizing alveolitis and bronchiolitis were present. Variable edema and hyaline membrane formation, alveolar epithelial hyperplasia, and secondary bacterial pneumonia were also seen. Large basophilic intranuclear inclusions were present in bronchiolar and alveolar epithelial cells in all 26 cases. In 4 of 8 cases examined ultrastructurally typical intranuclear paracrystalline arrays of adenoviral virions were demonstrated. Intranuclear inclusion bodies were also observed occasionally in bile duct and pancreatic duct epithelium. Simian adenoviral pneumonia can be a spontaneous disease problem in laboratory-reared primates and offers excellent potential as an animal model of human adenoviral pneumonia.", "contents": "Simian adenoviral pneumonia. In the past 6 years we have encountered 26 cases of fatal adenoviral pneumonia in six species of simian primates. O these, 22 animals were between 11 and 38 days old at the time of death, and pneumonia was the primary clinical disease. The spectrum of clinical disease varied from peracute fatal disease to inapparent disease with seroconversion. In one outbreak involving 4 infants housed together in an isolation unit, simian virus 11 was isolated from 3 of the infants and seroconversion occurred in all 4. At necropsy the lungs were voluminous, with firm gray areas of consolidation. On histopathologic examination, severe patchy necrotizing alveolitis and bronchiolitis were present. Variable edema and hyaline membrane formation, alveolar epithelial hyperplasia, and secondary bacterial pneumonia were also seen. Large basophilic intranuclear inclusions were present in bronchiolar and alveolar epithelial cells in all 26 cases. In 4 of 8 cases examined ultrastructurally typical intranuclear paracrystalline arrays of adenoviral virions were demonstrated. Intranuclear inclusion bodies were also observed occasionally in bile duct and pancreatic duct epithelium. Simian adenoviral pneumonia can be a spontaneous disease problem in laboratory-reared primates and offers excellent potential as an animal model of human adenoviral pneumonia."}
{"id": "PMID:206148", "title": "Insulin binding and effects in isolated soleus muscle of lean and obese mice.", "content": "To get some insight into the mechanisms of insulin resistance in obesity, insulin binding and biological effects were investigated in soleus muscles isolated from normal and obese mice. Basal and insulin-stimulated 2-deoxyglucose uptake were measured at the steady state of insulin binding. The results were consistent with the concept of spare receptors, i.e., maximal insulin effect was achieved when only about 20% of total receptors was occupied. When similar studies were applied to muscles of gold thioglucose obese or genetically obese (ob/ob) mice, and compared to lean controls: a) insulin binding was decreased; b) the insulin dose-response curve of 2-deoxyglucose uptake was shifted to the right; c) maximally insulin-stimulated 2-deoxyglucose uptake, glycolysis, and glycogen synthesis were markedly decreased. Insulin binding and effects returned toward normal after a 40-h fast in obese mice. These results point to two loci for the insulin resistance of skeletal muscle in obesity: 1) a decrease in the number of insulin receptors, which results in a diminished insulin sensitivity; and 2) one or more alterations beyond receptor that are responsible for the decreased responsiveness of the tissue to insulin and appear to play a major role in the insulin resistance of muscle in obesity.", "contents": "Insulin binding and effects in isolated soleus muscle of lean and obese mice. To get some insight into the mechanisms of insulin resistance in obesity, insulin binding and biological effects were investigated in soleus muscles isolated from normal and obese mice. Basal and insulin-stimulated 2-deoxyglucose uptake were measured at the steady state of insulin binding. The results were consistent with the concept of spare receptors, i.e., maximal insulin effect was achieved when only about 20% of total receptors was occupied. When similar studies were applied to muscles of gold thioglucose obese or genetically obese (ob/ob) mice, and compared to lean controls: a) insulin binding was decreased; b) the insulin dose-response curve of 2-deoxyglucose uptake was shifted to the right; c) maximally insulin-stimulated 2-deoxyglucose uptake, glycolysis, and glycogen synthesis were markedly decreased. Insulin binding and effects returned toward normal after a 40-h fast in obese mice. These results point to two loci for the insulin resistance of skeletal muscle in obesity: 1) a decrease in the number of insulin receptors, which results in a diminished insulin sensitivity; and 2) one or more alterations beyond receptor that are responsible for the decreased responsiveness of the tissue to insulin and appear to play a major role in the insulin resistance of muscle in obesity."}
{"id": "PMID:206149", "title": "Instantaneous changes of alpha-adrenoceptor affinity caused by moderate cooling in canine cutaneous veins.", "content": "Experiments were performed to investigate why cooling augments the contractile responses of superficial veins, but depresses that of deep limb veins. Rings of dog's saphenous veins were mounted in an organ chamber for isometric tension recording. Cooling (from 37 to 24 degrees C) depressed the tissular uptake of [3H]norepinephrine and potentiated the contraction caused by norepinephrine and sympathetic nerve stimulation; this potentiation persisted after inhibition of the disposition mechanisms for the catecholamine and in the presence of ouabain or iproveratril. The affinity of the alpha adrenoceptors, to judge from the KA values for norepinephrine and from the pA2 values for the competitive antagonist phentolamine, was significantly greater at 24 degrees C than at 37 degrees C. Thus, an instantaneous change in the affinity of alpha adrenoceptors explains the augmented response of the cutaneous veins to adrenergic stimulation. By contrast, cooling depressed the response of femoral veins to norepinephrine and did not significantly affect the affinity of alpha adrenoceptors in this preparation, indicating that the temperature sensitivity of alpha adrenoceptors in cutaneous veins is related to chronic exposure to variations in local temperature.", "contents": "Instantaneous changes of alpha-adrenoceptor affinity caused by moderate cooling in canine cutaneous veins. Experiments were performed to investigate why cooling augments the contractile responses of superficial veins, but depresses that of deep limb veins. Rings of dog's saphenous veins were mounted in an organ chamber for isometric tension recording. Cooling (from 37 to 24 degrees C) depressed the tissular uptake of [3H]norepinephrine and potentiated the contraction caused by norepinephrine and sympathetic nerve stimulation; this potentiation persisted after inhibition of the disposition mechanisms for the catecholamine and in the presence of ouabain or iproveratril. The affinity of the alpha adrenoceptors, to judge from the KA values for norepinephrine and from the pA2 values for the competitive antagonist phentolamine, was significantly greater at 24 degrees C than at 37 degrees C. Thus, an instantaneous change in the affinity of alpha adrenoceptors explains the augmented response of the cutaneous veins to adrenergic stimulation. By contrast, cooling depressed the response of femoral veins to norepinephrine and did not significantly affect the affinity of alpha adrenoceptors in this preparation, indicating that the temperature sensitivity of alpha adrenoceptors in cutaneous veins is related to chronic exposure to variations in local temperature."}
{"id": "PMID:206150", "title": "Enhanced phosphorylation of myocardial sarcoplasmic reticulum in experimental hyperthyroidism.", "content": "Calcium transport by cardiac sarcoplasmic reticulum (SR) was compared in hyperthyroid (HT) and euthyroid (ET) rats. Both Ca2+ uptake (97 +/- 3.1 nmol/mg per min in HT vs. 63 +/- 2.9 nmol/mg per min in ET, P less than 0.01) and CA2+ -stimulated ATPase activity (61 +/- 4.1 vs. 37 +/- 1.6 nmol Pi/mg per min, P less than 0.01) were higher in the thyroxine-treated animals. These changes were accompanied by enhanced cyclic AMP-dependent phosphorylation of cardiac SR in hyperthyroid rats (180 +/- 4.3 pmol Pi/mg per min vs. 117 +/- 4.2 pmol Pi/mg per min, P less than 0.01). SDS-polyacrylamide gel electrophoresis of cardiac SR showed that phosphorylation of a 22,000-dalton protein (phospholamban) primarily accounted for the differences between the two groups. There was no difference in the rate of SR dephosphorylation by endogenous phosphoprotein phosphatase between HT and ET rats. Differences in cyclic AMP-dependent phosphorylation between the two groups were blunted in the presence of excess exogenous cyclic AMP-dependent protein kinase. These results suggest that increased levels or activity of endogenous cyclic AMP-dependent protein kinases may partially explain enhanced calcium transport by the cardiac SR of hyperthyroid animals.", "contents": "Enhanced phosphorylation of myocardial sarcoplasmic reticulum in experimental hyperthyroidism. Calcium transport by cardiac sarcoplasmic reticulum (SR) was compared in hyperthyroid (HT) and euthyroid (ET) rats. Both Ca2+ uptake (97 +/- 3.1 nmol/mg per min in HT vs. 63 +/- 2.9 nmol/mg per min in ET, P less than 0.01) and CA2+ -stimulated ATPase activity (61 +/- 4.1 vs. 37 +/- 1.6 nmol Pi/mg per min, P less than 0.01) were higher in the thyroxine-treated animals. These changes were accompanied by enhanced cyclic AMP-dependent phosphorylation of cardiac SR in hyperthyroid rats (180 +/- 4.3 pmol Pi/mg per min vs. 117 +/- 4.2 pmol Pi/mg per min, P less than 0.01). SDS-polyacrylamide gel electrophoresis of cardiac SR showed that phosphorylation of a 22,000-dalton protein (phospholamban) primarily accounted for the differences between the two groups. There was no difference in the rate of SR dephosphorylation by endogenous phosphoprotein phosphatase between HT and ET rats. Differences in cyclic AMP-dependent phosphorylation between the two groups were blunted in the presence of excess exogenous cyclic AMP-dependent protein kinase. These results suggest that increased levels or activity of endogenous cyclic AMP-dependent protein kinases may partially explain enhanced calcium transport by the cardiac SR of hyperthyroid animals."}
{"id": "PMID:206151", "title": "Interaction of acetylcholine and epinephrine on heart cyclic AMP-dependent protein kinase.", "content": "In the isolated perfused rat heart, epinephrine produced a rapid, concentration-dependent increase in cyclic adenosine 3',5'-monophosphate (cAMP), activation of cAMP-dependent protein kinase, activation of phosphorylase, and increase in contractile force. At epinephrine concentrations of 1 micron or less, acetylcholine antagonized all these beta-adrenergic effects and also increased cyclic guanosine 3',5'-monophosphate (cGMP) levels. When used alone, acetylcholine produced a rapid elevation of cGMP and markedly diminished contractile force but did not significantly lower basal cAMP levels or cAMP-dependent protein kinase activity. The data suggest that changes in cAMP-dependent protein kinase activity can explain the antagonism of epinephrine-induced activation of phosphorylase by acetylcholine, but cannot completely account for the inhibitory effect of the cholinergic agent on contractile force.", "contents": "Interaction of acetylcholine and epinephrine on heart cyclic AMP-dependent protein kinase. In the isolated perfused rat heart, epinephrine produced a rapid, concentration-dependent increase in cyclic adenosine 3',5'-monophosphate (cAMP), activation of cAMP-dependent protein kinase, activation of phosphorylase, and increase in contractile force. At epinephrine concentrations of 1 micron or less, acetylcholine antagonized all these beta-adrenergic effects and also increased cyclic guanosine 3',5'-monophosphate (cGMP) levels. When used alone, acetylcholine produced a rapid elevation of cGMP and markedly diminished contractile force but did not significantly lower basal cAMP levels or cAMP-dependent protein kinase activity. The data suggest that changes in cAMP-dependent protein kinase activity can explain the antagonism of epinephrine-induced activation of phosphorylase by acetylcholine, but cannot completely account for the inhibitory effect of the cholinergic agent on contractile force."}
{"id": "PMID:206154", "title": "Ephaptic transmission in squid giant axons.", "content": "Some characteristics of ephaptic transmission of action potentials were investigated with squid giant axons. For these studies two isolated axons were placed side by side or, on occasion, a single long axon was looped to form an \"ephapse\" between the axon trunk and one of its main branches. Extracellular potentials measured adjacent to axons surrounded by a very restricted volume of liquid ranged up to 80 mV in magnitude and had a shape similar to that of the membrane current. Intracellular records of the same axon regions show small voltage deflections; however, the transmembrane voltage (Vm = Vi - Vo) has the appearance of normally propagated action potentials. Ephaptic transmission of action potentials is possible when the ephaptic region is submerged in oil, as well as when the region is immersed in low-calcium solutions. When the speed of the propagated action potential is lowered by replacing the normal artifical seawater (ASW) with low-sodium ASW, some ephaptic effects are enhanced. It is concluded that in regions in which axons are confined by restricted extracellular volume, the large extracellular voltage changes arising during the passage of an action potential in one can cause ephaptic excitation in another.", "contents": "Ephaptic transmission in squid giant axons. Some characteristics of ephaptic transmission of action potentials were investigated with squid giant axons. For these studies two isolated axons were placed side by side or, on occasion, a single long axon was looped to form an \"ephapse\" between the axon trunk and one of its main branches. Extracellular potentials measured adjacent to axons surrounded by a very restricted volume of liquid ranged up to 80 mV in magnitude and had a shape similar to that of the membrane current. Intracellular records of the same axon regions show small voltage deflections; however, the transmembrane voltage (Vm = Vi - Vo) has the appearance of normally propagated action potentials. Ephaptic transmission of action potentials is possible when the ephaptic region is submerged in oil, as well as when the region is immersed in low-calcium solutions. When the speed of the propagated action potential is lowered by replacing the normal artifical seawater (ASW) with low-sodium ASW, some ephaptic effects are enhanced. It is concluded that in regions in which axons are confined by restricted extracellular volume, the large extracellular voltage changes arising during the passage of an action potential in one can cause ephaptic excitation in another."}
{"id": "PMID:206155", "title": "Herpes virus infection alters electrical parameters of heart cell aggregates.", "content": "The spontaneous beat of embryonic heart cell aggregates in culture grew gradually weaker and stopped about 18 h after inoculation with herpes simplex virus 1 (HSV-1). Before electrical activity ceased, maximal action potential upstroke velocity fell to about 20% of control values, whereas overshoot and plateau duration declined about 50%. Maximal diastolic potential was reduced by only about 10%. Eighteen hours after viral inoculation, specific membrane resistance and intercellular coupling were measured in quiescent aggregates with injected current pulses passed between two widely spaced intracellular electrodes. These parameters were unaltered as compared with control aggregates. However, pairs of infected aggregates brought into contact required 8 h to synchronize their beats; mock-inoculated aggregates coupled in less than 1 h. It is concluded that the cell surface alterations caused by HSV-1 infection specifically reduce both fast and slow inward currents and interfere with the formation of new nexal junctions.", "contents": "Herpes virus infection alters electrical parameters of heart cell aggregates. The spontaneous beat of embryonic heart cell aggregates in culture grew gradually weaker and stopped about 18 h after inoculation with herpes simplex virus 1 (HSV-1). Before electrical activity ceased, maximal action potential upstroke velocity fell to about 20% of control values, whereas overshoot and plateau duration declined about 50%. Maximal diastolic potential was reduced by only about 10%. Eighteen hours after viral inoculation, specific membrane resistance and intercellular coupling were measured in quiescent aggregates with injected current pulses passed between two widely spaced intracellular electrodes. These parameters were unaltered as compared with control aggregates. However, pairs of infected aggregates brought into contact required 8 h to synchronize their beats; mock-inoculated aggregates coupled in less than 1 h. It is concluded that the cell surface alterations caused by HSV-1 infection specifically reduce both fast and slow inward currents and interfere with the formation of new nexal junctions."}
{"id": "PMID:206156", "title": "Effect of synthetic C-terminal fragments of hGH on insulin release by isolated islets.", "content": "Synthetic fragments representing the C-terminal end of the growth hormone molecule have been tested for their direct in vitro effects on insulin release by isolated rat islets of Langerhans. hGH 177-191 caused a dose-related potentiation of glucose-induced insulin release, whereas the peptide by itself caused no stimulation of insulin release from the islets. The rate curves constructed for insulin secretion as a function of extracellular glucose concentration showed that the Km for glucose is not altered in the presence of the peptide, but that the Vmax of secretion is increased. Significant potentiation of insulin release by the peptide was seen only at high extracellular concentrations of glucose. Measurement of cAMP levels in islets showed that the peptide caused no significant alteration of cAMP levels while still potentiating insulin release. It was therefore concluded that the mechanism of potentiation of insulin release by the peptide may be independent of the changes in cAMP levels in islets. hGH 172-191, too, caused potentiation of glucose-stimulated insulin release from islets, whereas hGH 179-191 was not active in this report.", "contents": "Effect of synthetic C-terminal fragments of hGH on insulin release by isolated islets. Synthetic fragments representing the C-terminal end of the growth hormone molecule have been tested for their direct in vitro effects on insulin release by isolated rat islets of Langerhans. hGH 177-191 caused a dose-related potentiation of glucose-induced insulin release, whereas the peptide by itself caused no stimulation of insulin release from the islets. The rate curves constructed for insulin secretion as a function of extracellular glucose concentration showed that the Km for glucose is not altered in the presence of the peptide, but that the Vmax of secretion is increased. Significant potentiation of insulin release by the peptide was seen only at high extracellular concentrations of glucose. Measurement of cAMP levels in islets showed that the peptide caused no significant alteration of cAMP levels while still potentiating insulin release. It was therefore concluded that the mechanism of potentiation of insulin release by the peptide may be independent of the changes in cAMP levels in islets. hGH 172-191, too, caused potentiation of glucose-stimulated insulin release from islets, whereas hGH 179-191 was not active in this report."}
{"id": "PMID:206157", "title": "Role of cyclic AMP in rat aortic microsomal phosphorylation and calcium uptake.", "content": "The role of adenosine 3',5'-monophosphate (cyclic AMP)-dependent membrane phosphorylation in the regulation of microsomal calcium transport in rat aortic smooth muscle was studied. Cyclic AMP-dependent protein kinase augmented the phosphorylation of serine residues in a microsomal protein component with a molecular weight of about 44,000 (determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and the majority of 32P incorporation was in serine residue(s). The phosphorylated protein had stability characteristics of a phosphoester. The phosphorylated substrate was not extracted from the trichloroacetic acid (TCA) precipitate with organic solvents or by suspension in hot TCA; and the demonstrated hydroxylamine insensitivity suggested that the substrate was not lipid or nucleic acid. Intrinsic phosphoprotein phosphatase cleaved the labeled phosphate from the cyclic AMP-stimulated microsomes in the first 5 min of incubation. Microsomes phosphorylated in the presence of 1 micron cyclic AMP or 1 micron cyclic AMP plus 0.1 mg/ml protein kinase exhibited enhanced calcium uptake. We suggest that reversible phosphorylation of microsomal membranes may play an important role in the regulation of aortic microsomal calcium transport by cyclic AMP.", "contents": "Role of cyclic AMP in rat aortic microsomal phosphorylation and calcium uptake. The role of adenosine 3',5'-monophosphate (cyclic AMP)-dependent membrane phosphorylation in the regulation of microsomal calcium transport in rat aortic smooth muscle was studied. Cyclic AMP-dependent protein kinase augmented the phosphorylation of serine residues in a microsomal protein component with a molecular weight of about 44,000 (determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and the majority of 32P incorporation was in serine residue(s). The phosphorylated protein had stability characteristics of a phosphoester. The phosphorylated substrate was not extracted from the trichloroacetic acid (TCA) precipitate with organic solvents or by suspension in hot TCA; and the demonstrated hydroxylamine insensitivity suggested that the substrate was not lipid or nucleic acid. Intrinsic phosphoprotein phosphatase cleaved the labeled phosphate from the cyclic AMP-stimulated microsomes in the first 5 min of incubation. Microsomes phosphorylated in the presence of 1 micron cyclic AMP or 1 micron cyclic AMP plus 0.1 mg/ml protein kinase exhibited enhanced calcium uptake. We suggest that reversible phosphorylation of microsomal membranes may play an important role in the regulation of aortic microsomal calcium transport by cyclic AMP."}
{"id": "PMID:206158", "title": "Protein kinase regulation of cardiac phosphorylase activity and contractility.", "content": "The relationship between cAMP-dependent protein kinase activity and epinephrine-produced activation of phosphorylase and increase in contractility was investigated in the intact working rat heart. Epinephrine was administered as a bolus into the superior vena cava of open-chest preparations and the hearts were rapidly frozen. cAMP increased within 5 s and returned to control within 20-30 s. Protein kinase and phosphorylase kinase activity ratios increased transiently with the same time course as that for cAMP. The phosphorylase activity ratio and the rate of left ventricular pressure development increased maximally within 15 s and returned to control in 30-60 s. Continuous infusion of epinephrine caused a sustained elevation of the protein kinase. Free catalytic protein kinase activity increased proportionately with the dose of epinephrine. The beta-adrenergic blocking agent, practolol, had no effect on the basal levels of the five parameters studied, but did prevent the epinephrine-produced increases. The results suggest that the time course of cAMP-dependent protein kinase activation is appropriate if this enzyme is to play a role in the catecholamine-induced increase in both glycogenolysis and contractility in the in vivo heart.", "contents": "Protein kinase regulation of cardiac phosphorylase activity and contractility. The relationship between cAMP-dependent protein kinase activity and epinephrine-produced activation of phosphorylase and increase in contractility was investigated in the intact working rat heart. Epinephrine was administered as a bolus into the superior vena cava of open-chest preparations and the hearts were rapidly frozen. cAMP increased within 5 s and returned to control within 20-30 s. Protein kinase and phosphorylase kinase activity ratios increased transiently with the same time course as that for cAMP. The phosphorylase activity ratio and the rate of left ventricular pressure development increased maximally within 15 s and returned to control in 30-60 s. Continuous infusion of epinephrine caused a sustained elevation of the protein kinase. Free catalytic protein kinase activity increased proportionately with the dose of epinephrine. The beta-adrenergic blocking agent, practolol, had no effect on the basal levels of the five parameters studied, but did prevent the epinephrine-produced increases. The results suggest that the time course of cAMP-dependent protein kinase activation is appropriate if this enzyme is to play a role in the catecholamine-induced increase in both glycogenolysis and contractility in the in vivo heart."}
{"id": "PMID:206159", "title": "Behavior of axenic IP-106 strain of Entamoeba histolytica in the golden hamster.", "content": "Strain IP-106 of Entamoeba histolytica was isolated 12 yr ago from a case of amebic dysentery and has been maintained in axenic culture for the past 11 yr. Hamsters were inoculated intrahepatically, intraperitoneally, and intracecally with 6.5, 5.0, and 8.0 X 10(4) axenic trophozoites, respectively. With the first two routes of inoculation all the animals developed liver abscesses, and most developed amebic metastases to other sites. After intracecal inoculation only 3 out of 6 animals developed abscesses at the primary site and metastases to other sites. Most numerous metastases were obtained following intrahepatic inoculation. Intrahepatic inoculation with 1 and 2 X 10(4) axenic amebae resulted in an increase in the size of the liver abscess for a period of 2 wk and its apparent total resorption by day 17 post-inoculation, accompanied by a corresponding gain of body weight. With 4 and 6 X 10(4) amebae there was a steady increase of the size of the liver abscess and corresponding loss of body weight. High antiamebic indirect hemagglutination titers were observed only on day 17 post infection in animals inoculated with 2, 4, and 6 X 10(4) amebae. The extent of amebic metastases was roughly proportional to the size of the inoculum.", "contents": "Behavior of axenic IP-106 strain of Entamoeba histolytica in the golden hamster. Strain IP-106 of Entamoeba histolytica was isolated 12 yr ago from a case of amebic dysentery and has been maintained in axenic culture for the past 11 yr. Hamsters were inoculated intrahepatically, intraperitoneally, and intracecally with 6.5, 5.0, and 8.0 X 10(4) axenic trophozoites, respectively. With the first two routes of inoculation all the animals developed liver abscesses, and most developed amebic metastases to other sites. After intracecal inoculation only 3 out of 6 animals developed abscesses at the primary site and metastases to other sites. Most numerous metastases were obtained following intrahepatic inoculation. Intrahepatic inoculation with 1 and 2 X 10(4) axenic amebae resulted in an increase in the size of the liver abscess for a period of 2 wk and its apparent total resorption by day 17 post-inoculation, accompanied by a corresponding gain of body weight. With 4 and 6 X 10(4) amebae there was a steady increase of the size of the liver abscess and corresponding loss of body weight. High antiamebic indirect hemagglutination titers were observed only on day 17 post infection in animals inoculated with 2, 4, and 6 X 10(4) amebae. The extent of amebic metastases was roughly proportional to the size of the inoculum."}
{"id": "PMID:206161", "title": "NAD nucleosidase of Agkistrodon bilineatus venom.", "content": "NAD nucleosidase (NAD glycohydrolase, EC 3.2.2.5) activity in Agkistrodon bilineatus venom was observed. Using the cyanide assay method at pH 7.9, lyophilized crude venom had an activity of 0.19 units/mg. Chromatography of the crude venom on DEAE Sephadex A-50 with ammonium acetate buffer by two stage elution yielded 13 fractions. Peak NAD nucleosidase activity occurred at Fraction X. Crude venom and Fraction X NAD nucleosidase activities were thermolabile.", "contents": "NAD nucleosidase of Agkistrodon bilineatus venom. NAD nucleosidase (NAD glycohydrolase, EC 3.2.2.5) activity in Agkistrodon bilineatus venom was observed. Using the cyanide assay method at pH 7.9, lyophilized crude venom had an activity of 0.19 units/mg. Chromatography of the crude venom on DEAE Sephadex A-50 with ammonium acetate buffer by two stage elution yielded 13 fractions. Peak NAD nucleosidase activity occurred at Fraction X. Crude venom and Fraction X NAD nucleosidase activities were thermolabile."}
{"id": "PMID:206162", "title": "The treatment of operable breast cancer in the elderly female.", "content": "The treatment of operable breast cancer in eighty-two patients older than seventy years was analyzed. The cancers were treated at an advanced stage and the axilla was involved as frequently as in younger women. The factors influencing survival differ because of competing mortalities from heart disease and stroke. The risks are discussed in relation to life expectancy and treatment method.", "contents": "The treatment of operable breast cancer in the elderly female. The treatment of operable breast cancer in eighty-two patients older than seventy years was analyzed. The cancers were treated at an advanced stage and the axilla was involved as frequently as in younger women. The factors influencing survival differ because of competing mortalities from heart disease and stroke. The risks are discussed in relation to life expectancy and treatment method."}
{"id": "PMID:206168", "title": "Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin and beta-bungarotoxin.", "content": "Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin, and beta-bungarotoxin were studied in 12 chickens using the sciatic-gastrocnemius nerve-muscle preparation to elucidate the mechanism of action of each drug. Modification by the toxins of neuromuscular effects of edrophonium depended on the level of block pre-established by the toxins. Edrophonium-induced augmentation of muscle twitch (\"facilitation\") was decreased by both toxins. As the block reached 50 per cent, the facilitation was nearly abolished. Edrophonium-induced contracture of the muscle was blocked by alpha-bungarotoxin only. At 25 per cent block, it was no longer observable in five of six preparations. Beta-bungarotoxin enhanced the contracture. At complete block, the contracture reached 156 (SE 11, n = 6) per cent of control. The authors conclude that edrophonium facilitates neuromuscular transmission by a prejunctional mechanism and causes contracture of the chicken muscle by a post-junctional activation. The beta-bungarotoxin-blocked nerve-muscle preparation of the chicken is a model of acute denervation potentially useful for the study of drug effects on the postjunctional membrane.", "contents": "Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin and beta-bungarotoxin. Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin, and beta-bungarotoxin were studied in 12 chickens using the sciatic-gastrocnemius nerve-muscle preparation to elucidate the mechanism of action of each drug. Modification by the toxins of neuromuscular effects of edrophonium depended on the level of block pre-established by the toxins. Edrophonium-induced augmentation of muscle twitch (\"facilitation\") was decreased by both toxins. As the block reached 50 per cent, the facilitation was nearly abolished. Edrophonium-induced contracture of the muscle was blocked by alpha-bungarotoxin only. At 25 per cent block, it was no longer observable in five of six preparations. Beta-bungarotoxin enhanced the contracture. At complete block, the contracture reached 156 (SE 11, n = 6) per cent of control. The authors conclude that edrophonium facilitates neuromuscular transmission by a prejunctional mechanism and causes contracture of the chicken muscle by a post-junctional activation. The beta-bungarotoxin-blocked nerve-muscle preparation of the chicken is a model of acute denervation potentially useful for the study of drug effects on the postjunctional membrane."}
{"id": "PMID:206169", "title": "[Basal cell adenomas of the salivary glands. Analysis of 7 cases and review of the literature. Comparative study with cylindromas].", "content": "Basal cell adenomas, of which 7 cases are reported here together with 63 others collected in the literature, are benign tumours of the salivary glands, preferentially localised in the parotid and in the upper lip. Mobile, non-ulcerated and painless, these nodules with an average diameter of 2 cm are well circumscribed, fleshy or cystic. Their morphology is characterised by the proliferation of uniform, small cells, with scarcely visible cytoplasm, arranged in layers, cords and canals, which may be ectasic or cystic. Peripheral elements, individualising these different structures, are arranged in palissades and are regularly surrounded by a basal membrane. The histological analogies between basal cell adenomas and cylindromas merely reflect their ultrastructural similarities, cellular as well as architectural. These two neoplasms may be distinguished on the basis of two essential morphological criteria:--basal cell adenomas are well circumscribed, whilst cylindromas are invasive;--the cells in adenomas are closely juxtaposed, endowing the various structures of these tumours with a dense appearance, whilst cylindroma cells are generally separated by clear spaces corresponding to extreme development of the intercellular spaces.", "contents": "[Basal cell adenomas of the salivary glands. Analysis of 7 cases and review of the literature. Comparative study with cylindromas]. Basal cell adenomas, of which 7 cases are reported here together with 63 others collected in the literature, are benign tumours of the salivary glands, preferentially localised in the parotid and in the upper lip. Mobile, non-ulcerated and painless, these nodules with an average diameter of 2 cm are well circumscribed, fleshy or cystic. Their morphology is characterised by the proliferation of uniform, small cells, with scarcely visible cytoplasm, arranged in layers, cords and canals, which may be ectasic or cystic. Peripheral elements, individualising these different structures, are arranged in palissades and are regularly surrounded by a basal membrane. The histological analogies between basal cell adenomas and cylindromas merely reflect their ultrastructural similarities, cellular as well as architectural. These two neoplasms may be distinguished on the basis of two essential morphological criteria:--basal cell adenomas are well circumscribed, whilst cylindromas are invasive;--the cells in adenomas are closely juxtaposed, endowing the various structures of these tumours with a dense appearance, whilst cylindroma cells are generally separated by clear spaces corresponding to extreme development of the intercellular spaces."}
{"id": "PMID:206170", "title": "Cross reactions of normal bovine sera with foot-and-mouth disease virus: incidence, duration, and effect of shipping stress.", "content": "Serum samples were obtained from 30 Hereford steers in an area known to be free of foot-and-mouth disease (FMD) viruses as follows: before shipment and 4 times during a 70-day period after shipment; the sera were tested for the presence of cross-reacting antibody to various viruses. Percentages of sera containing cross-reacting antibody to FMD virus detected by the plaque-reduction neutralization and the radial immunodiffusion techniques were higher for the FMD viruses Asia and SAT I5 than for the FMD viruses A5, O1, and C1. Cross-reacting antibody was usually of low titer and usually present in only 1 or 2 consecutive serum samples. The incidence of cross reactions increased after stress of shipping and thus an infective agent may be responsible. These results were compared with results from sera collected from Herefords and Holstein-Friesians in a 2nd area; results did not indicate that Herefords have an excess of cross reactions with FMD viruses.", "contents": "Cross reactions of normal bovine sera with foot-and-mouth disease virus: incidence, duration, and effect of shipping stress. Serum samples were obtained from 30 Hereford steers in an area known to be free of foot-and-mouth disease (FMD) viruses as follows: before shipment and 4 times during a 70-day period after shipment; the sera were tested for the presence of cross-reacting antibody to various viruses. Percentages of sera containing cross-reacting antibody to FMD virus detected by the plaque-reduction neutralization and the radial immunodiffusion techniques were higher for the FMD viruses Asia and SAT I5 than for the FMD viruses A5, O1, and C1. Cross-reacting antibody was usually of low titer and usually present in only 1 or 2 consecutive serum samples. The incidence of cross reactions increased after stress of shipping and thus an infective agent may be responsible. These results were compared with results from sera collected from Herefords and Holstein-Friesians in a 2nd area; results did not indicate that Herefords have an excess of cross reactions with FMD viruses."}
{"id": "PMID:206173", "title": "Isolation of transmissible gastroenteritis virus from pharyngeal swabs obtained from sows at slaughter.", "content": "A virologic survey was conducted to determine the frequency of transmissible gastroenteritis (TGE) virus infection in farm-raised sows. Pharyngeal swab specimens collected in an abattoir were examined for TGE virus by inoculation onto swine-testes cell culures. The virus was detected in 61 (3%) of a sample of 2,058 Iowa sows after slaughter. All TGE viral isolates, given orally to 2- or 3-day-old pigs, caused acute gastroenteritis and in some cases death. All pigs that recovered from illness had serum antibody to TGE virus.", "contents": "Isolation of transmissible gastroenteritis virus from pharyngeal swabs obtained from sows at slaughter. A virologic survey was conducted to determine the frequency of transmissible gastroenteritis (TGE) virus infection in farm-raised sows. Pharyngeal swab specimens collected in an abattoir were examined for TGE virus by inoculation onto swine-testes cell culures. The virus was detected in 61 (3%) of a sample of 2,058 Iowa sows after slaughter. All TGE viral isolates, given orally to 2- or 3-day-old pigs, caused acute gastroenteritis and in some cases death. All pigs that recovered from illness had serum antibody to TGE virus."}
{"id": "PMID:206172", "title": "Comparison of the lesions of Aleutian disease in mink and hypergammaglobulinemia in ferrets.", "content": "Gross and microscopic lesions of Aleutian disease (AD) in mink and hypergammaglobulinemia in ferrets were compared. Both conditions were characterized by widespread proliferation of plasma cells, but proliferation was more prominent in mink infected with AD. Arteritis did not occur in hypergammaglobulinemic ferrets. Minimal or no glomerular alterations occurred in infected ferrets, but were severe in mink infected with AD. Bile duct proliferation was more prominent in diseased mink. Tissue alterations suggested that AD in Aleutian genotype mink is more rapidly progressive than is AD in ferrets, causing overt clinical disease and death. In contrast, hypergammaglobulinemia in ferrets appeared to progress more slowly, with little clinical evidence of disease. This is probably the result of a paucity of glomerular lesions in ferrets. Possible mechanisms to explain the differences in the development of lesions are discussed.", "contents": "Comparison of the lesions of Aleutian disease in mink and hypergammaglobulinemia in ferrets. Gross and microscopic lesions of Aleutian disease (AD) in mink and hypergammaglobulinemia in ferrets were compared. Both conditions were characterized by widespread proliferation of plasma cells, but proliferation was more prominent in mink infected with AD. Arteritis did not occur in hypergammaglobulinemic ferrets. Minimal or no glomerular alterations occurred in infected ferrets, but were severe in mink infected with AD. Bile duct proliferation was more prominent in diseased mink. Tissue alterations suggested that AD in Aleutian genotype mink is more rapidly progressive than is AD in ferrets, causing overt clinical disease and death. In contrast, hypergammaglobulinemia in ferrets appeared to progress more slowly, with little clinical evidence of disease. This is probably the result of a paucity of glomerular lesions in ferrets. Possible mechanisms to explain the differences in the development of lesions are discussed."}
{"id": "PMID:206174", "title": "Unusual intra-abdominal metastases from carcinoma of the lung.", "content": "Eleven patients with bronchogenic carcinoma underwent surgical treatment of metastatic abdominal visceral lesions. Successful surgical palliation was achieved in nine. In eight patients intraabdominal metastasis marked the first clinical sign of spread of the primary tumor outside the chest. The longest interval following diagnosis of the primary lung lesion and the appearance of the abdominal symptoms due to metastatic disease was three and one-half years.", "contents": "Unusual intra-abdominal metastases from carcinoma of the lung. Eleven patients with bronchogenic carcinoma underwent surgical treatment of metastatic abdominal visceral lesions. Successful surgical palliation was achieved in nine. In eight patients intraabdominal metastasis marked the first clinical sign of spread of the primary tumor outside the chest. The longest interval following diagnosis of the primary lung lesion and the appearance of the abdominal symptoms due to metastatic disease was three and one-half years."}
{"id": "PMID:206176", "title": "[Multicentric reticulo-histiocytosis; review of recent literature (since 1969)].", "content": "The review of recent literature (since 1969) shows 35 cases of multicentric reticulo-histiocytosis. This entity was first described as a dermatological disease, then as a dermatoarthritis. It is in fact a systemic disease which can involve many organs but is sometimes monosymptomatic. Its fatal outcome is, sometimes, the result of a disseminated neoplasia or a lymphoma. Its clinical and microscopic features allow to distinguish it from solitary reticulo-histiocytoma, generalized eruptive histiocytoma, congenital reticulo-histiocytosis of Hashimoto and Pritzker and familial histiocytic dermato-arthritis of Zayid.", "contents": "[Multicentric reticulo-histiocytosis; review of recent literature (since 1969)]. The review of recent literature (since 1969) shows 35 cases of multicentric reticulo-histiocytosis. This entity was first described as a dermatological disease, then as a dermatoarthritis. It is in fact a systemic disease which can involve many organs but is sometimes monosymptomatic. Its fatal outcome is, sometimes, the result of a disseminated neoplasia or a lymphoma. Its clinical and microscopic features allow to distinguish it from solitary reticulo-histiocytoma, generalized eruptive histiocytoma, congenital reticulo-histiocytosis of Hashimoto and Pritzker and familial histiocytic dermato-arthritis of Zayid."}
{"id": "PMID:206178", "title": "[Liver cell carcinoma associated with oral contraceptives (author's transl)].", "content": "A new case report of primary malignant hepatic tumor during a long term oral contraception is presented. A direct role of contraceptives drugs cannot be claimed because of little cases reported. Nevertheless, appearance of carcinogenic compounds in predisposed women may be evoked.", "contents": "[Liver cell carcinoma associated with oral contraceptives (author's transl)]. A new case report of primary malignant hepatic tumor during a long term oral contraception is presented. A direct role of contraceptives drugs cannot be claimed because of little cases reported. Nevertheless, appearance of carcinogenic compounds in predisposed women may be evoked."}
{"id": "PMID:206179", "title": "[Glucocorticoid receptors in mammary tumors in PS and C3H mouse strains (author's transl)].", "content": "Specific binding of glucocorticoids was characterized in mammary tumors and cells derived from C3H and PS mice. The binding protein satisfied all the general criteria of hormone receptors namely high affinity and binding specificity for glucocorticoids (KD congruent to 2.5 nM) for 3H Dexamethasone and limited number of binding sites (congruent to 150 femtomoles/mg Protein). The hormonal regulation of these receptors will be reported. The production of viral particles of type A and B was increased by glucocorticoids in the PS MT1 and PS MT2 cell lines derived from the PS tumors.", "contents": "[Glucocorticoid receptors in mammary tumors in PS and C3H mouse strains (author's transl)]. Specific binding of glucocorticoids was characterized in mammary tumors and cells derived from C3H and PS mice. The binding protein satisfied all the general criteria of hormone receptors namely high affinity and binding specificity for glucocorticoids (KD congruent to 2.5 nM) for 3H Dexamethasone and limited number of binding sites (congruent to 150 femtomoles/mg Protein). The hormonal regulation of these receptors will be reported. The production of viral particles of type A and B was increased by glucocorticoids in the PS MT1 and PS MT2 cell lines derived from the PS tumors."}
{"id": "PMID:206175", "title": "Effects of putative transmitters on afferent cochlear transmission.", "content": "Putative transmitters and related substances were perfused through the guinea pig scala tympani while monitoring the compound action potential of the cochlear nerve (AP) and the cochlear microphonic potential. Various substances were then ranked according to their ability to reduce the AP. The more active compounds ranked: methysergide (1 mM) greater than ATP (10 mM) = tyramine (10 mM) greater than salicylate (10 mM) greater than bicuculline (10 mM) greater than asparate (10 mM) greater than glutamate (10 mM) greater than citrate (10 mM) greater than dextrose (100 mM) greater than glycine (100 mM) greater than GABA (100 mM) greater than prostaglandin E2 (1 mM) greater than serotonin (10 mM). The activity of substances at 100 mM indicates a physical, osmotic change in the cochlear structure. Activity at 10 mM and 1 mM indicated afferent transmitter-like activity for the putative transmitters and interference with the endogenous transmitter for related substances. It is concluded that several substances can be eliminated as afferent transmitter candidates, while others warrant further examination.", "contents": "Effects of putative transmitters on afferent cochlear transmission. Putative transmitters and related substances were perfused through the guinea pig scala tympani while monitoring the compound action potential of the cochlear nerve (AP) and the cochlear microphonic potential. Various substances were then ranked according to their ability to reduce the AP. The more active compounds ranked: methysergide (1 mM) greater than ATP (10 mM) = tyramine (10 mM) greater than salicylate (10 mM) greater than bicuculline (10 mM) greater than asparate (10 mM) greater than glutamate (10 mM) greater than citrate (10 mM) greater than dextrose (100 mM) greater than glycine (100 mM) greater than GABA (100 mM) greater than prostaglandin E2 (1 mM) greater than serotonin (10 mM). The activity of substances at 100 mM indicates a physical, osmotic change in the cochlear structure. Activity at 10 mM and 1 mM indicated afferent transmitter-like activity for the putative transmitters and interference with the endogenous transmitter for related substances. It is concluded that several substances can be eliminated as afferent transmitter candidates, while others warrant further examination."}
{"id": "PMID:206180", "title": "[Effect of estradiol-17 beta on the somatrotroph cells of the adenohypophysis in the newt (author's transl)].", "content": "The somatotroph cells of the female newt's adenohypophysis are characterized by PAS positive, acidophils, electron dense large inclusions (4-6 micrometer). The apparition of these inclusions has been studied in females during the puberty. A correlation between the ovary stages and apparition, number and ultrastructural aspects (paracrystalline arrangement) of the inclusions is established. Same inclusion genesis and aspects has been observed after treatment of young newt males by oestradiol-17 beta (5 mg/liter diluted in the aquarium water). It is concluded that endocrine activity of ovaries may be responsible of the inclusions occurence in the females.", "contents": "[Effect of estradiol-17 beta on the somatrotroph cells of the adenohypophysis in the newt (author's transl)]. The somatotroph cells of the female newt's adenohypophysis are characterized by PAS positive, acidophils, electron dense large inclusions (4-6 micrometer). The apparition of these inclusions has been studied in females during the puberty. A correlation between the ovary stages and apparition, number and ultrastructural aspects (paracrystalline arrangement) of the inclusions is established. Same inclusion genesis and aspects has been observed after treatment of young newt males by oestradiol-17 beta (5 mg/liter diluted in the aquarium water). It is concluded that endocrine activity of ovaries may be responsible of the inclusions occurence in the females."}
{"id": "PMID:206181", "title": "[A case of virilizing adrenal cortical adenoma whose steroid profile evokes a partial 21-hydroxylase deficiency (author's transl)].", "content": "The C19 and C21 urinary steroids from a virilizing adrenal tumour with high levels of plasma 17 alpha-hydroxyprogesterone and its urinary metabolites have been identified and quantitated gas chromatography and mass spectrometry of sephadex fractions of the total urinary extract. A of the fifty-five identified steroids thirteen were compounds not found before in such a case. The actiology of the apparent 21-steroid hydroxtlase deficiency is discussed at the light of these analytical results and of the hormonogenesis enzymatic induction of the tumour biopsy.", "contents": "[A case of virilizing adrenal cortical adenoma whose steroid profile evokes a partial 21-hydroxylase deficiency (author's transl)]. The C19 and C21 urinary steroids from a virilizing adrenal tumour with high levels of plasma 17 alpha-hydroxyprogesterone and its urinary metabolites have been identified and quantitated gas chromatography and mass spectrometry of sephadex fractions of the total urinary extract. A of the fifty-five identified steroids thirteen were compounds not found before in such a case. The actiology of the apparent 21-steroid hydroxtlase deficiency is discussed at the light of these analytical results and of the hormonogenesis enzymatic induction of the tumour biopsy."}
{"id": "PMID:206182", "title": "[Virilizing tumours of the adrenal cortex with unimpaired menstruation (author's transl)].", "content": "Virilizing adenomas of the adrenal cortex entail, typically, hirsutism, amenorrhea and hypertrophy of the clitoris. We report two cases of adrenal adenoma, both revealed by hirsutism and significant biological features, but both without any alteration of the menstrual cycle. One of our 2 patients showed moderate hypertrophy of the clitoris. In the first patient, the tumour has been located thanks to dexamethasone--modifiying adrenal secretion, and in the second patient, thanks to angiography. These two cases reported are a warning never to neglect more hirsutism, even, when unobstrusive, and always to undertake minimal hormonal investigations.", "contents": "[Virilizing tumours of the adrenal cortex with unimpaired menstruation (author's transl)]. Virilizing adenomas of the adrenal cortex entail, typically, hirsutism, amenorrhea and hypertrophy of the clitoris. We report two cases of adrenal adenoma, both revealed by hirsutism and significant biological features, but both without any alteration of the menstrual cycle. One of our 2 patients showed moderate hypertrophy of the clitoris. In the first patient, the tumour has been located thanks to dexamethasone--modifiying adrenal secretion, and in the second patient, thanks to angiography. These two cases reported are a warning never to neglect more hirsutism, even, when unobstrusive, and always to undertake minimal hormonal investigations."}
{"id": "PMID:206183", "title": "Skeletal age and submaximal working capacity in boys.", "content": "Skeletal age (SA) and Vo2 at a heart rate of 130 (Vo130) during work on a bicycle ergometer were measured in 237 boys 8-18 years of age. Analysis indicates that Vo130 is well correlated with SA, but also is equally well correlated with chronological age (CA), height and body weight. Age-specific correlations show that Vo130 is associated with SA from 12 through 16 years of age. Partialing out SA results in a significant decrease in the correlations of either height or weight with Vo130 only in the 12-16 year subgroup. The total common variance explained in Vo130 when regressed over CA, height and weight is affected by the presence of SA only in the 12-16 age subset. In spite of the high degree of multicollinearity among the independent variates, correlation data seem to indicate that SA and Vo130 have a slightly higher degree of relationship circumpuberally, i.e. between 12 and 16 years of age.", "contents": "Skeletal age and submaximal working capacity in boys. Skeletal age (SA) and Vo2 at a heart rate of 130 (Vo130) during work on a bicycle ergometer were measured in 237 boys 8-18 years of age. Analysis indicates that Vo130 is well correlated with SA, but also is equally well correlated with chronological age (CA), height and body weight. Age-specific correlations show that Vo130 is associated with SA from 12 through 16 years of age. Partialing out SA results in a significant decrease in the correlations of either height or weight with Vo130 only in the 12-16 year subgroup. The total common variance explained in Vo130 when regressed over CA, height and weight is affected by the presence of SA only in the 12-16 age subset. In spite of the high degree of multicollinearity among the independent variates, correlation data seem to indicate that SA and Vo130 have a slightly higher degree of relationship circumpuberally, i.e. between 12 and 16 years of age."}
{"id": "PMID:206185", "title": "Osteomalacia and disorders of vitamin D metabolism.", "content": "A rapidly growing understanding of the biochemical and physiological processes that underlie the metabolism of vitamin D has provided new insights into the pathogenesis of oestomalacia. Many of the vitamin D--resistant osteomalacia syndromes can now be explained on the basis of defects in the metabolic conversion of vitamin D to the biologically active dihydroxylated metabolite 1,25(OH)2D and perhaps, in some instances, to impairement of the actions of 1,25(OH)2D on target tissues. The availability of this new information has made possible the synthesis of 1-hydroxylated forms of the vitamin for therapeutic use in states of vitamin D resistance. Although many questions regarding the pathogenesis and most effective approaches in the management of osteomalacia remain unanswered, considerable progress has been made in this direction as a result of continued research on the subject.", "contents": "Osteomalacia and disorders of vitamin D metabolism. A rapidly growing understanding of the biochemical and physiological processes that underlie the metabolism of vitamin D has provided new insights into the pathogenesis of oestomalacia. Many of the vitamin D--resistant osteomalacia syndromes can now be explained on the basis of defects in the metabolic conversion of vitamin D to the biologically active dihydroxylated metabolite 1,25(OH)2D and perhaps, in some instances, to impairement of the actions of 1,25(OH)2D on target tissues. The availability of this new information has made possible the synthesis of 1-hydroxylated forms of the vitamin for therapeutic use in states of vitamin D resistance. Although many questions regarding the pathogenesis and most effective approaches in the management of osteomalacia remain unanswered, considerable progress has been made in this direction as a result of continued research on the subject."}
{"id": "PMID:206186", "title": "Dialysis versus transplantation in the treatment of end-stage renal disease.", "content": "Both dialysis and kidney transplantation are effective techniques for prolonging life in ESRD. Because dialysis therapy does not effect replacement of the metabolic functions of the kidney, it is less tha perfect. Successful transplantation that replaces all of the aspects of renal function is the treatment of choice. Successful transplantation is highly dependent upon the availability of a suitable donor and the appropriate tissue match, which remains a problem. Present immunosuppressive therapy required to prevent the immunoresponse causing rejection of the renal allograft is a tool too dull for the job. Since all immunoresponse is suppressed, infections are common, as are the multiple complications of cortical steroid therapy. For the dialysis patient, development of more compact effective dialysis apparatus and particularly the availability of replacement therapy hold promise. New approaches to diminishing the immune response to the graft without impairing that to microorganisms may well effect improvement in graft survival as will increasing knowledge of factors other than HLA antigens in the immunologic reaction. Development of an effective method for arresting the progress of glomerulonephritis before it reaches end-stage renal failure would obviate the necessity for dialysis or transplant therapy in appoximately two thirds of ESRD patients.", "contents": "Dialysis versus transplantation in the treatment of end-stage renal disease. Both dialysis and kidney transplantation are effective techniques for prolonging life in ESRD. Because dialysis therapy does not effect replacement of the metabolic functions of the kidney, it is less tha perfect. Successful transplantation that replaces all of the aspects of renal function is the treatment of choice. Successful transplantation is highly dependent upon the availability of a suitable donor and the appropriate tissue match, which remains a problem. Present immunosuppressive therapy required to prevent the immunoresponse causing rejection of the renal allograft is a tool too dull for the job. Since all immunoresponse is suppressed, infections are common, as are the multiple complications of cortical steroid therapy. For the dialysis patient, development of more compact effective dialysis apparatus and particularly the availability of replacement therapy hold promise. New approaches to diminishing the immune response to the graft without impairing that to microorganisms may well effect improvement in graft survival as will increasing knowledge of factors other than HLA antigens in the immunologic reaction. Development of an effective method for arresting the progress of glomerulonephritis before it reaches end-stage renal failure would obviate the necessity for dialysis or transplant therapy in appoximately two thirds of ESRD patients."}
{"id": "PMID:206188", "title": "Contractile proteins in cell structure and function.", "content": "1. The cytoplasm of cells is a colloidal network of contractile proteins. Actin filaments are the major components of this network. Other contractile proteins interact with these filaments to create structural rigidity and movement. 2. The structure and function of contractile proteins is striated muscles is well characterized and thus provides a good example for extrapolitation to an analysis of contractile-protein structure and function of nonmuscle cells. However, the interaction of contractile proteins of various cells may be unique. 3. The study of contractile proteins in cells other than muscle has distinct difficulties: (a) The proteins are present in much lower concentration than in muscle, and only a few cell types are obtainable for study in quantities comparable to muscle. (b) Proteolysis and other detriments may be more severe in nonmuscle cells. (c) The organization of contractile proteins is difficult to define in nonmuscle cells. (d) The effort is diffuse; investigations examine a wide variety of different, or less commonly the same, cells. Reflecting these difficulties, a catalogue of putative nonmuscle cell fucntions related to contractile proteins reveals no one system to be definitively worked out. Nevertheless, the ubiquity of contractile proteins and the obvious importance of their intractions presages increasing relevancy for physiology and medicine.", "contents": "Contractile proteins in cell structure and function. 1. The cytoplasm of cells is a colloidal network of contractile proteins. Actin filaments are the major components of this network. Other contractile proteins interact with these filaments to create structural rigidity and movement. 2. The structure and function of contractile proteins is striated muscles is well characterized and thus provides a good example for extrapolitation to an analysis of contractile-protein structure and function of nonmuscle cells. However, the interaction of contractile proteins of various cells may be unique. 3. The study of contractile proteins in cells other than muscle has distinct difficulties: (a) The proteins are present in much lower concentration than in muscle, and only a few cell types are obtainable for study in quantities comparable to muscle. (b) Proteolysis and other detriments may be more severe in nonmuscle cells. (c) The organization of contractile proteins is difficult to define in nonmuscle cells. (d) The effort is diffuse; investigations examine a wide variety of different, or less commonly the same, cells. Reflecting these difficulties, a catalogue of putative nonmuscle cell fucntions related to contractile proteins reveals no one system to be definitively worked out. Nevertheless, the ubiquity of contractile proteins and the obvious importance of their intractions presages increasing relevancy for physiology and medicine."}
{"id": "PMID:206198", "title": "[Interferonogenic activity of gossypol, a low-molecular substance].", "content": "The interferonogenic activity of gossipol, a low molecular substance of polyphenolic nature was shown in the cell cultures of chick embryos and organisms of mice. Pronounced prophylactic efficiency of the drug in mice with experimental infection caused by the West Nile virus was found. Definite parallelism between the intensity of interferonogenesis and the protection level from the virus affection due to the use of gossipol in mice was noted. Difference between gossipol and other known low molecular inductors of interferon, such as dyes, tyloron, propandinamine is discussed. The possibility of using gossipol as an antiviral drug is presumed.", "contents": "[Interferonogenic activity of gossypol, a low-molecular substance]. The interferonogenic activity of gossipol, a low molecular substance of polyphenolic nature was shown in the cell cultures of chick embryos and organisms of mice. Pronounced prophylactic efficiency of the drug in mice with experimental infection caused by the West Nile virus was found. Definite parallelism between the intensity of interferonogenesis and the protection level from the virus affection due to the use of gossipol in mice was noted. Difference between gossipol and other known low molecular inductors of interferon, such as dyes, tyloron, propandinamine is discussed. The possibility of using gossipol as an antiviral drug is presumed."}
{"id": "PMID:206199", "title": "Mechanistic studies of polyene enhancement of interferon production by polyriboinosinic-polyribocytidylic acid.", "content": "The production of interferon by polyriboinosinic-polyribocytidylic acid [poly(I) . poly(C)] and poly(I) . poly(C)-diethylaminoethyl-dextran in L929 cells was enhanced from 10 to 100 times by polyene macrolides, including amphotericin B (AmB), AmB methyl ester, nystatin, and filipin. AmB and its water-soluble methyl ester were the most effective; retinol, a nonmacrolide polyene, was ineffective. Interferon induction by Newcastle disease virus was not enhanced by AmB. The kinetics of interferon production were not markedly altered by AmB. Polyenes and poly(I) . poly(C)-diethylaminoethyl-dextran did not need to be present on cells simultaneously to enhance interferon production. Pretreatment with polyenes was as effective as simultaneous addition. Even treatment of washed cells, several hours after removal of poly(I) . poly(C)-diethylaminoethyl-dextran, resulted in enhancement of interferon production. AmB did not appear to form a macromolecular complex with poly(I) . poly(C) in that neither the ultraviolet absorption spectrum nor the melting point of poly(I) . poly(C) was altered by mixing with AmB. Isotopic studies indicated that AmB did not enhance binding of poly(I) . poly(C) to cells. Since the macrolide polyenes have been demonstrated to bind to cell membrane sterols with subsequent alterations in membrane permeability barriers, they may enhance interferon production by increasing cell penetration of poly(I) . poly(C).", "contents": "Mechanistic studies of polyene enhancement of interferon production by polyriboinosinic-polyribocytidylic acid. The production of interferon by polyriboinosinic-polyribocytidylic acid [poly(I) . poly(C)] and poly(I) . poly(C)-diethylaminoethyl-dextran in L929 cells was enhanced from 10 to 100 times by polyene macrolides, including amphotericin B (AmB), AmB methyl ester, nystatin, and filipin. AmB and its water-soluble methyl ester were the most effective; retinol, a nonmacrolide polyene, was ineffective. Interferon induction by Newcastle disease virus was not enhanced by AmB. The kinetics of interferon production were not markedly altered by AmB. Polyenes and poly(I) . poly(C)-diethylaminoethyl-dextran did not need to be present on cells simultaneously to enhance interferon production. Pretreatment with polyenes was as effective as simultaneous addition. Even treatment of washed cells, several hours after removal of poly(I) . poly(C)-diethylaminoethyl-dextran, resulted in enhancement of interferon production. AmB did not appear to form a macromolecular complex with poly(I) . poly(C) in that neither the ultraviolet absorption spectrum nor the melting point of poly(I) . poly(C) was altered by mixing with AmB. Isotopic studies indicated that AmB did not enhance binding of poly(I) . poly(C) to cells. Since the macrolide polyenes have been demonstrated to bind to cell membrane sterols with subsequent alterations in membrane permeability barriers, they may enhance interferon production by increasing cell penetration of poly(I) . poly(C)."}
{"id": "PMID:206200", "title": "Inhibition of herpesvirus replication and herpesvirus-induced deoxyribonucleic acid polymerase by phosphonoformate.", "content": "Phosphonoformate was found to be an inhibitor of the deoxyribonucleic acid polymerase induced by the herpesvirus of turkeys. The apparent inhibition constants were 1 to 3 muM. Phosphonoformate was also able to block the replication in cell culture of Marek's disease herpesvirus, the herpesvirus of turkeys, and herpes simplex virus. It was as effective as phosphonoacetate. Phosphonoformate was not an effective inhibitor of a phosphonoacetate-resistant mutant of the herpesvirus of turkeys nor of its induced deoxyribonucleic acid polymerase.", "contents": "Inhibition of herpesvirus replication and herpesvirus-induced deoxyribonucleic acid polymerase by phosphonoformate. Phosphonoformate was found to be an inhibitor of the deoxyribonucleic acid polymerase induced by the herpesvirus of turkeys. The apparent inhibition constants were 1 to 3 muM. Phosphonoformate was also able to block the replication in cell culture of Marek's disease herpesvirus, the herpesvirus of turkeys, and herpes simplex virus. It was as effective as phosphonoacetate. Phosphonoformate was not an effective inhibitor of a phosphonoacetate-resistant mutant of the herpesvirus of turkeys nor of its induced deoxyribonucleic acid polymerase."}
{"id": "PMID:206201", "title": "Antiviral effects of amphotericin B methyl ester.", "content": "The methyl ester of amphotericin B (AME) is water soluble, retains antifungal activity, and is significantly less toxic in mammals than amphotericin B. In contrast to amphotericin B, which is not water soluble, AME exhibits antiviral effects against vesicular stomatitis virus, herpes simplex virus types 1 and 2, Sindbis virus, and vaccinia virus in a plaque reduction assay. No antiviral effects could be demonstrated against the unenveloped adenovirus type 4 or echovirus type 11. The extent of virus inactivation was found to be dependent upon the AME concentration, contact time, and temperature. No consistent effect of the virus concentration on the probability of plaque-forming unit inactivation could be determined. The antiviral effects of AME were partially antagonized by the presence of serum. Binding of AME to vesicular stomatitis virus was demonstrated by the comigration of drug and virus in linear sucrose gradients. AME represents a new class of antiviral agents with activity at concentrations relevant to therapeutics. Sterol components of the host cell membrane that become incorporated into the viral envelope are postulated as the site of reaction with AME.", "contents": "Antiviral effects of amphotericin B methyl ester. The methyl ester of amphotericin B (AME) is water soluble, retains antifungal activity, and is significantly less toxic in mammals than amphotericin B. In contrast to amphotericin B, which is not water soluble, AME exhibits antiviral effects against vesicular stomatitis virus, herpes simplex virus types 1 and 2, Sindbis virus, and vaccinia virus in a plaque reduction assay. No antiviral effects could be demonstrated against the unenveloped adenovirus type 4 or echovirus type 11. The extent of virus inactivation was found to be dependent upon the AME concentration, contact time, and temperature. No consistent effect of the virus concentration on the probability of plaque-forming unit inactivation could be determined. The antiviral effects of AME were partially antagonized by the presence of serum. Binding of AME to vesicular stomatitis virus was demonstrated by the comigration of drug and virus in linear sucrose gradients. AME represents a new class of antiviral agents with activity at concentrations relevant to therapeutics. Sterol components of the host cell membrane that become incorporated into the viral envelope are postulated as the site of reaction with AME."}
{"id": "PMID:206202", "title": "Effect of amphotericin B methyl ester on vesicular stomatitis virus morphology.", "content": "The water-soluble methyl ester of amphotericin B inactivates vesicular stomatitis virus in association with morphological alterations of the envelope.", "contents": "Effect of amphotericin B methyl ester on vesicular stomatitis virus morphology. The water-soluble methyl ester of amphotericin B inactivates vesicular stomatitis virus in association with morphological alterations of the envelope."}
{"id": "PMID:206203", "title": "Treatment of a murine cytomegalovirus infection with exogenous interferon, polyinosinic-polycytidylic acid, and polyinosinic-polycytidylic acid-poly-L-lysine complex.", "content": "Treatment of a cytomegalovirus infection of mice with exogenous murine interferon did not alter final mortality or mean day of death. Pretreatment with two interferon inducers significantly reduced mortality, but treatment initiated after infection was not effective.", "contents": "Treatment of a murine cytomegalovirus infection with exogenous interferon, polyinosinic-polycytidylic acid, and polyinosinic-polycytidylic acid-poly-L-lysine complex. Treatment of a cytomegalovirus infection of mice with exogenous murine interferon did not alter final mortality or mean day of death. Pretreatment with two interferon inducers significantly reduced mortality, but treatment initiated after infection was not effective."}
{"id": "PMID:206204", "title": "Role of sediment in the persistence of enteroviruses in the estuarine environment.", "content": "The survival of four enteroviruses commonly found in sewage effluents was examined when the viruses were adsorped to marine sediments in estuarine water and compared with virus survival in estuarine water alone. Echovirus 1, coxsackieviruses B3 and A9, and poliovirus 1 survived longer when associated with marine sediment. When the estuarine water was polluted with secondarily treated sewage effluent, virus survived for prolonged periods in sediments, but not in the overlaying estuarine water.", "contents": "Role of sediment in the persistence of enteroviruses in the estuarine environment. The survival of four enteroviruses commonly found in sewage effluents was examined when the viruses were adsorped to marine sediments in estuarine water and compared with virus survival in estuarine water alone. Echovirus 1, coxsackieviruses B3 and A9, and poliovirus 1 survived longer when associated with marine sediment. When the estuarine water was polluted with secondarily treated sewage effluent, virus survived for prolonged periods in sediments, but not in the overlaying estuarine water."}
{"id": "PMID:206205", "title": "New modification of Willis and Hobbs' method for identification of Clostridium perfringens.", "content": "A modification of the medium of Willis and Hobbs is described. All strains of Clostridium perfringens grown on it gave a positive lecithinase reaction. Some gave a negative reaction in the origin medium.", "contents": "New modification of Willis and Hobbs' method for identification of Clostridium perfringens. A modification of the medium of Willis and Hobbs is described. All strains of Clostridium perfringens grown on it gave a positive lecithinase reaction. Some gave a negative reaction in the origin medium."}
{"id": "PMID:206207", "title": "Viral infection as a precipitant of wheeze in children. Combined home and hospital study.", "content": "Sixteen children with asthma were studied for one year and viral isolation attempted during all episodes of wheezing. In 91 episodes investigated, 13 viruses were isolated (isolation rate 14%); whereas only one virus was isolated from 120 specimens taken when the children were symptom free. Rhinovirus was the commonest isolate and most were obtained during August, September, October. Episodes of wheezing associated with virus infection were not clinically different not more severe than those due to other precipitants.", "contents": "Viral infection as a precipitant of wheeze in children. Combined home and hospital study. Sixteen children with asthma were studied for one year and viral isolation attempted during all episodes of wheezing. In 91 episodes investigated, 13 viruses were isolated (isolation rate 14%); whereas only one virus was isolated from 120 specimens taken when the children were symptom free. Rhinovirus was the commonest isolate and most were obtained during August, September, October. Episodes of wheezing associated with virus infection were not clinically different not more severe than those due to other precipitants."}
{"id": "PMID:206210", "title": "Neonatal hyperammonaemia with complete absence of liver carbamyl phosphate synthetase activity.", "content": "Two newborn infants, male (A) and female (B), with lethal hyperammonaemia are described in the same family. In both, symptoms started on the second day of life. Lethargy and hypotonia were the most prominent initial findings and were followed by convulsions and coma. In both, blood ammonia levels rose to 570 mumol/u (795 microgram/100 ml) a few hours before death, which occurred on the third and fourth day of life respectively. Assay of liver urea cycle enzymes in baby B showed a complete absence of mitochondrial carbamyl phosphate synthetase activity.", "contents": "Neonatal hyperammonaemia with complete absence of liver carbamyl phosphate synthetase activity. Two newborn infants, male (A) and female (B), with lethal hyperammonaemia are described in the same family. In both, symptoms started on the second day of life. Lethargy and hypotonia were the most prominent initial findings and were followed by convulsions and coma. In both, blood ammonia levels rose to 570 mumol/u (795 microgram/100 ml) a few hours before death, which occurred on the third and fourth day of life respectively. Assay of liver urea cycle enzymes in baby B showed a complete absence of mitochondrial carbamyl phosphate synthetase activity."}
{"id": "PMID:206214", "title": "The surgical treatment of Wilms' tumor: results of the National Wilms' Tumor Study.", "content": "Surgical data derived from the 606 patients in the National Wilms' Tumor Study have been analyzed to determine the effect of surgical technique on results of treatment. In addition to surgical excision of the tumor, patients were treated with chemotherapy and radiation therapy according to the study protocol. Under these controlled conditions, certain aspects of surgical technique which have traditionally been thought to be important for success appear to be irrelevant. Physical characteristics of the tumor, preoperative rupture and vascular invasion by tumor were not associated with higher relapse rates. Large tumors, those with capsular infiltrations, and tumors with spread to lymph nodes higher recurrence rate. Operative spill increased the chance of abdominal recurrence. There was no evidence that early ligation of the renal vein was of value in prevention of recurrence, nor was incomplete removal of tumor associated with an increase in relapse rate. Although several critical factors of surgical technique were not studied, it is clear that others are not significant and need not be continued.", "contents": "The surgical treatment of Wilms' tumor: results of the National Wilms' Tumor Study. Surgical data derived from the 606 patients in the National Wilms' Tumor Study have been analyzed to determine the effect of surgical technique on results of treatment. In addition to surgical excision of the tumor, patients were treated with chemotherapy and radiation therapy according to the study protocol. Under these controlled conditions, certain aspects of surgical technique which have traditionally been thought to be important for success appear to be irrelevant. Physical characteristics of the tumor, preoperative rupture and vascular invasion by tumor were not associated with higher relapse rates. Large tumors, those with capsular infiltrations, and tumors with spread to lymph nodes higher recurrence rate. Operative spill increased the chance of abdominal recurrence. There was no evidence that early ligation of the renal vein was of value in prevention of recurrence, nor was incomplete removal of tumor associated with an increase in relapse rate. Although several critical factors of surgical technique were not studied, it is clear that others are not significant and need not be continued."}
{"id": "PMID:206215", "title": "Cholecystosonography for the diagnosis of cholecystolithiasis.", "content": "The gallbladder can be visualized by ultrasound (cholecystosonography) and gallstones seen as echo producing densities. Under cholecystosonographic observation the gallbladder can be demonstrated to contract following stimulation by cholecystokinin. This establishes patency of the cystic duct and excludes a diagnosis of acute obstructive cholecystopathy. The gallbladder has been identified in 84 of 86 patients. Stones have been identified sonographically in 64% of 42 patients with proven gallstones (75% of the last 20 cases). The gallbladder contracted following stimulation in 18 of 20 cases with a patent cystic duct. Cholecystosonography is simple, safe and economical. Cholecystonography with cholecystokinin stimulation is the first diagnostic study to be performed when cholecystolithiasis is suspected and the following circumstances exists: a) an acute right upper quadrant (RUQ) syndrome consistant with acute obstructive cholecystopathy. b) cholestasis or hepatic dysfunction. c) a history of allergy to contrast media. Cholecystosonography may detect gallstones in a gallbladder visualized by oral cholangiography when stones are of the same density as the contrast media.", "contents": "Cholecystosonography for the diagnosis of cholecystolithiasis. The gallbladder can be visualized by ultrasound (cholecystosonography) and gallstones seen as echo producing densities. Under cholecystosonographic observation the gallbladder can be demonstrated to contract following stimulation by cholecystokinin. This establishes patency of the cystic duct and excludes a diagnosis of acute obstructive cholecystopathy. The gallbladder has been identified in 84 of 86 patients. Stones have been identified sonographically in 64% of 42 patients with proven gallstones (75% of the last 20 cases). The gallbladder contracted following stimulation in 18 of 20 cases with a patent cystic duct. Cholecystosonography is simple, safe and economical. Cholecystonography with cholecystokinin stimulation is the first diagnostic study to be performed when cholecystolithiasis is suspected and the following circumstances exists: a) an acute right upper quadrant (RUQ) syndrome consistant with acute obstructive cholecystopathy. b) cholestasis or hepatic dysfunction. c) a history of allergy to contrast media. Cholecystosonography may detect gallstones in a gallbladder visualized by oral cholangiography when stones are of the same density as the contrast media."}
{"id": "PMID:206213", "title": "Sensory irritation and incapacitation evoked by thermal decomposition products of polymers and comparisons with known sensory irritants.", "content": "A decrease in respiratory rate in mice during exposure to irritating airborne chemicals has been utilized as a response parameter to characterize the degree of upper respiratory tract irritation (sensory irritation) to the thermal decomposition products of various polymers. These included polystyrene, polyvinyl chloride, flexible polyurethane foam, polytetrafluorethylene, a fiber glass reinforced polyester resin, and Douglas Fir. Each of the materials was thermally decomposed in a low-mass vertical furnace in an air atmosphere at a programmed heating rate of 20 degrees C/min. Mice, in groups of four, were exposed to graded concentrations of the thermal decomposition products of each of the above materials. Dose-response curves were obtained by utilizing the maximum percent decrease in respiratory rate as the response parameter during each exposure. Comparison of these dose-response curves with other sensory irritants such as chlorine, ammonia, hydrogen chloride, sulfur dioxide, and toluene diisocyanate gave an indication of the sensory irrtation potential of the thermal decomposition products of these various polymers versus that of well-known single airborne chemical irritants. Total stress and incapacitation of the organism during exposure to sensory irritants such as from the thermal decomposition products of synthetic polymers is discussed.", "contents": "Sensory irritation and incapacitation evoked by thermal decomposition products of polymers and comparisons with known sensory irritants. A decrease in respiratory rate in mice during exposure to irritating airborne chemicals has been utilized as a response parameter to characterize the degree of upper respiratory tract irritation (sensory irritation) to the thermal decomposition products of various polymers. These included polystyrene, polyvinyl chloride, flexible polyurethane foam, polytetrafluorethylene, a fiber glass reinforced polyester resin, and Douglas Fir. Each of the materials was thermally decomposed in a low-mass vertical furnace in an air atmosphere at a programmed heating rate of 20 degrees C/min. Mice, in groups of four, were exposed to graded concentrations of the thermal decomposition products of each of the above materials. Dose-response curves were obtained by utilizing the maximum percent decrease in respiratory rate as the response parameter during each exposure. Comparison of these dose-response curves with other sensory irritants such as chlorine, ammonia, hydrogen chloride, sulfur dioxide, and toluene diisocyanate gave an indication of the sensory irrtation potential of the thermal decomposition products of these various polymers versus that of well-known single airborne chemical irritants. Total stress and incapacitation of the organism during exposure to sensory irritants such as from the thermal decomposition products of synthetic polymers is discussed."}
{"id": "PMID:206216", "title": "Liver resection in children with hepatic neoplasms.", "content": "In the past ten years, 28 patients with primary tumors of the liver have been treated. There were 11 benign tumors, including four hamartomas, three patients with focal nodular hyperplasia, and two each with congenital cysts and hemangioma. Hamartomas and masses of focal nodular hyperplasia should be excised when possible, but both are benign lesions; therefore life threatening excisions at the porta hepatis should be avoided. Cysts are often resectable, but when occupying all lobes of the liver, they can be successfully managed by marsupialization into the free peritoneal cavity. If resectable, hemangiomas should be removed; when occupying most of the liver as they often do, patients may be subject to platelet trapping or to cardiac failure. In some instances these lesions have been controlled by steroids, radiation therapy or hepatic artery ligation. Of 17 malignant tumors seen, 12 proved to be hepatoblastomas. Nine of the 12 patients underwent liver resection, of whom four are cured, (33%). There were three children with hepatocellular carcinomas and two with embryonal rhabdomyosarcoma. One child from each of these groups is cured by surgical excision. At present the only known cures in children with primary malignant liver neoplasms have been achieved by operative removal.", "contents": "Liver resection in children with hepatic neoplasms. In the past ten years, 28 patients with primary tumors of the liver have been treated. There were 11 benign tumors, including four hamartomas, three patients with focal nodular hyperplasia, and two each with congenital cysts and hemangioma. Hamartomas and masses of focal nodular hyperplasia should be excised when possible, but both are benign lesions; therefore life threatening excisions at the porta hepatis should be avoided. Cysts are often resectable, but when occupying all lobes of the liver, they can be successfully managed by marsupialization into the free peritoneal cavity. If resectable, hemangiomas should be removed; when occupying most of the liver as they often do, patients may be subject to platelet trapping or to cardiac failure. In some instances these lesions have been controlled by steroids, radiation therapy or hepatic artery ligation. Of 17 malignant tumors seen, 12 proved to be hepatoblastomas. Nine of the 12 patients underwent liver resection, of whom four are cured, (33%). There were three children with hepatocellular carcinomas and two with embryonal rhabdomyosarcoma. One child from each of these groups is cured by surgical excision. At present the only known cures in children with primary malignant liver neoplasms have been achieved by operative removal."}
{"id": "PMID:206218", "title": "Disseminated Strongyloides stercoralis infection. Association with ectopic ACTH syndrome and depressed cell-mediated immunity.", "content": "A patient with disseminated Strongyloides stercoralis was evaluated to elucidate host factors that may have led to the development of this infection. The patient was found to have oat cell carcinoma with hypercortisolism produced by tumor adrenocorticotropic hormone. His serum contained a potent inhibitor of lymphocyte blastogenesis. This patient's high level of endogenous cortisol may have impaired lymphocyte function and thereby facilitated infection with S stercoralis.", "contents": "Disseminated Strongyloides stercoralis infection. Association with ectopic ACTH syndrome and depressed cell-mediated immunity. A patient with disseminated Strongyloides stercoralis was evaluated to elucidate host factors that may have led to the development of this infection. The patient was found to have oat cell carcinoma with hypercortisolism produced by tumor adrenocorticotropic hormone. His serum contained a potent inhibitor of lymphocyte blastogenesis. This patient's high level of endogenous cortisol may have impaired lymphocyte function and thereby facilitated infection with S stercoralis."}
{"id": "PMID:206222", "title": "Influence of cyclic 3',5'-adenosine monophosphate and adenosine on vascular reactivity.", "content": "cAMP, 5'-AMP and adenosine in doses of 1, 2 and 5 mg/kg i.v. in rats diminish vascular resistance in the hind limbs in vivo and in isolated limbs perfused with nutrient fluid containing adrenaline (A) (10(-3) M), slowing action of the heart and lowering blood pressure. After administration of cAMP, 5'-AMP and adenosine (5 mg/kg), vasoconstricting action of noradrenaline (NA) and A was depressed, and the vasodilating action of isoprenaline (I) was enhanced. The changes in blood pressure observed after administration of the tested adenosine compounds were not blocked by phentolamine, but after I were blocked by propranolol. cAMP, 5'-AMP and adenosine had no influence on the drop in blood pressure elicited by acetylcholine. The results indicate that cAMP, 5'-AMP and adenosine increase reactivity of beta-receptors of the sympathetic system in the blood vessels and modify the action of catecholamines on blood vessels.", "contents": "Influence of cyclic 3',5'-adenosine monophosphate and adenosine on vascular reactivity. cAMP, 5'-AMP and adenosine in doses of 1, 2 and 5 mg/kg i.v. in rats diminish vascular resistance in the hind limbs in vivo and in isolated limbs perfused with nutrient fluid containing adrenaline (A) (10(-3) M), slowing action of the heart and lowering blood pressure. After administration of cAMP, 5'-AMP and adenosine (5 mg/kg), vasoconstricting action of noradrenaline (NA) and A was depressed, and the vasodilating action of isoprenaline (I) was enhanced. The changes in blood pressure observed after administration of the tested adenosine compounds were not blocked by phentolamine, but after I were blocked by propranolol. cAMP, 5'-AMP and adenosine had no influence on the drop in blood pressure elicited by acetylcholine. The results indicate that cAMP, 5'-AMP and adenosine increase reactivity of beta-receptors of the sympathetic system in the blood vessels and modify the action of catecholamines on blood vessels."}
{"id": "PMID:206223", "title": "Influence of phenylephrine on levels of cyclic 3',5'-AMP in the heart of rats in vivo.", "content": "In the course of an investigation into the mode of action of phenylephrine using the radioimmunoisotope method, its influence on levels of cyclic 3'5'-AMP in the heart of rats was studied. Phenylephrine in the dose of 1 microgram/kg/min after five minutes lowered levels of this nucleotide by about 20%. Phenylephrine also inhibited the influence of theophyline, an inhibitor of phosphodiesterase which raises levels of c-AMP. The results suggest that the drop in c-AMP after phenylephrine is connected with lowered activity of adenyl cyclase, but do not exclude the possiblity of an interaction between theophylline and phenylephrine acting on phosphodiesterase, which could be referred to the observed effect.", "contents": "Influence of phenylephrine on levels of cyclic 3',5'-AMP in the heart of rats in vivo. In the course of an investigation into the mode of action of phenylephrine using the radioimmunoisotope method, its influence on levels of cyclic 3'5'-AMP in the heart of rats was studied. Phenylephrine in the dose of 1 microgram/kg/min after five minutes lowered levels of this nucleotide by about 20%. Phenylephrine also inhibited the influence of theophyline, an inhibitor of phosphodiesterase which raises levels of c-AMP. The results suggest that the drop in c-AMP after phenylephrine is connected with lowered activity of adenyl cyclase, but do not exclude the possiblity of an interaction between theophylline and phenylephrine acting on phosphodiesterase, which could be referred to the observed effect."}
{"id": "PMID:206224", "title": "Investigation of the beta-adrenergic system in regulation of immunologic responses.", "content": "The influence of pharmacologic stimulation and blocking of the beta-adrenergic system on appearance of PF and RF cells, and intralymphocytic levels of cAMP were investigated. Stimulation of the beta-adrenergic receptor exerted an immunosuppressive effect, reflected by the numbers of PFC and RFC and raised levels of cAMP. Inhibition of the adrenergic beta-receptor stimulated immunologic responses and lowered levels of cAMP in lymphocytes. Confirmation of a specific adrenergic mechanism was provided by the absence of an effect of stimulation after prior blocking of the receptor. The possibility of a nonspecific membrane effect of beta-adrenergic drugs is discussed.", "contents": "Investigation of the beta-adrenergic system in regulation of immunologic responses. The influence of pharmacologic stimulation and blocking of the beta-adrenergic system on appearance of PF and RF cells, and intralymphocytic levels of cAMP were investigated. Stimulation of the beta-adrenergic receptor exerted an immunosuppressive effect, reflected by the numbers of PFC and RFC and raised levels of cAMP. Inhibition of the adrenergic beta-receptor stimulated immunologic responses and lowered levels of cAMP in lymphocytes. Confirmation of a specific adrenergic mechanism was provided by the absence of an effect of stimulation after prior blocking of the receptor. The possibility of a nonspecific membrane effect of beta-adrenergic drugs is discussed."}
{"id": "PMID:206225", "title": "Adrenergic regulation of phosphorolysis and hydrolysis of glycogen in smooth muscle of rabbit stomach in situ.", "content": "In smooth muscle of rabbit stomachs, activities of hydrolytic and phosphorolytic enzymes of glycogen degradation under the influence of agents stimulating and blocking adrenergic alpha and beta-receptors were studied. The results indicate that beta-adrenergic receptor in smooth muscle activated not only phosphorolytic, but also hydrolytic degradation of glycogen, and the alpha-adrenergic receptor only inhibited phosphorolysis but had no influence on hydrolysis of glycogen.", "contents": "Adrenergic regulation of phosphorolysis and hydrolysis of glycogen in smooth muscle of rabbit stomach in situ. In smooth muscle of rabbit stomachs, activities of hydrolytic and phosphorolytic enzymes of glycogen degradation under the influence of agents stimulating and blocking adrenergic alpha and beta-receptors were studied. The results indicate that beta-adrenergic receptor in smooth muscle activated not only phosphorolytic, but also hydrolytic degradation of glycogen, and the alpha-adrenergic receptor only inhibited phosphorolysis but had no influence on hydrolysis of glycogen."}
{"id": "PMID:206226", "title": "Amyloid formation in insulinoma.", "content": "Local amyloid depositions were investigated with electron microscopy in a functioning beta cell adenoma of the pancreas. Beta granule-containing neoplastic cells adjoining small amyloid depositions were shown to have cellular invaginations containing radiating amyloid bundles, indicating the neoplastic cells were involved in the formation of amyloid. Seen in the larger mayloid depositions were attenuated, thin, cellular processes of the neoplastic cells, separating the amyloid stroma into globules. The globular separations of the amyloid correlated well with the light-microscopic globular appearance of amyloid stroma. Possible mechanisms are discussed for the amyloid deposition of insulinoma with relation to amyloidogenesis of other types of amyloidosis.", "contents": "Amyloid formation in insulinoma. Local amyloid depositions were investigated with electron microscopy in a functioning beta cell adenoma of the pancreas. Beta granule-containing neoplastic cells adjoining small amyloid depositions were shown to have cellular invaginations containing radiating amyloid bundles, indicating the neoplastic cells were involved in the formation of amyloid. Seen in the larger mayloid depositions were attenuated, thin, cellular processes of the neoplastic cells, separating the amyloid stroma into globules. The globular separations of the amyloid correlated well with the light-microscopic globular appearance of amyloid stroma. Possible mechanisms are discussed for the amyloid deposition of insulinoma with relation to amyloidogenesis of other types of amyloidosis."}
{"id": "PMID:206227", "title": "Intranuclear fibrillary inclusions in influenza pneumonia.", "content": "Electron microscopical study of the lung tissue from a 75-year-old man who died of influenza pneumonia (A/Victoria/RI/76) demonstrated fibrillary inclusions in the nuclei of many alveolar lining cells, in bronchial epithelial cells, and also in endothelial cells. These inclusions were morphologically different from those previously reported in experimental animals. In view of previous experimental studies indicating the necessity of nuclear participation in the replication of influenza virus, these inclusions may be virus-induced structures. Also, possibly the presence of these inclusions in the nuclei of many endothelial cells might be indicative of endothelial damage of microvessels and may be a pathogenetically important factor in influenza pneumonia.", "contents": "Intranuclear fibrillary inclusions in influenza pneumonia. Electron microscopical study of the lung tissue from a 75-year-old man who died of influenza pneumonia (A/Victoria/RI/76) demonstrated fibrillary inclusions in the nuclei of many alveolar lining cells, in bronchial epithelial cells, and also in endothelial cells. These inclusions were morphologically different from those previously reported in experimental animals. In view of previous experimental studies indicating the necessity of nuclear participation in the replication of influenza virus, these inclusions may be virus-induced structures. Also, possibly the presence of these inclusions in the nuclei of many endothelial cells might be indicative of endothelial damage of microvessels and may be a pathogenetically important factor in influenza pneumonia."}
{"id": "PMID:206228", "title": "Electroneurographic evidence of polyneuropathy in chronic liver disease.", "content": "An electroneurographic study performed on the peripheral nerves of 25 patients with severe cirrhosis following viral hepatitis showed slight slowing (P greater than 0.05) of motor conduction velocity (CV) and significant diminution (P less than 0.001) of sensory CV and mixed sensorimotor-evoked potentials, associated with a significant decrease in the amplitude of sensory evoked potentials. The slowing was about equal in the distal (digital) and in the proximal segments of the same nerve. A mixed axonal degeneration and segmental demyelination is presumed to explain these findings. The CV measurements proved helpful for an early diagnosis of hepatic polyneuropathy showing subjective symptoms in the subclinical stage.", "contents": "Electroneurographic evidence of polyneuropathy in chronic liver disease. An electroneurographic study performed on the peripheral nerves of 25 patients with severe cirrhosis following viral hepatitis showed slight slowing (P greater than 0.05) of motor conduction velocity (CV) and significant diminution (P less than 0.001) of sensory CV and mixed sensorimotor-evoked potentials, associated with a significant decrease in the amplitude of sensory evoked potentials. The slowing was about equal in the distal (digital) and in the proximal segments of the same nerve. A mixed axonal degeneration and segmental demyelination is presumed to explain these findings. The CV measurements proved helpful for an early diagnosis of hepatic polyneuropathy showing subjective symptoms in the subclinical stage."}
{"id": "PMID:206229", "title": "Growth comparisons of avian infectious bronchitis virus strains in organ cultures of chicken tissues.", "content": "Six strains of avian infectious bronchitis virus (IBV) were used to inoculate explants of a range of 15 chicken tissues and virus growth kinetics observed over a period of 96 hours thereafter. Similar patterns of virus production were given by all 6 strains from explants of any particular tissue such as the nasal turbinates, trachea, lung, air sacs and oviduct. Nevertheless, significant differences in behaviour between strains were noted for different tissues and in the efficiency with which certain tissues produced virus. It is suggested that the method has a potential value in determining the virulence of different strains of IBV by comparing their pathogenesis of chicken tissues in vitro.", "contents": "Growth comparisons of avian infectious bronchitis virus strains in organ cultures of chicken tissues. Six strains of avian infectious bronchitis virus (IBV) were used to inoculate explants of a range of 15 chicken tissues and virus growth kinetics observed over a period of 96 hours thereafter. Similar patterns of virus production were given by all 6 strains from explants of any particular tissue such as the nasal turbinates, trachea, lung, air sacs and oviduct. Nevertheless, significant differences in behaviour between strains were noted for different tissues and in the efficiency with which certain tissues produced virus. It is suggested that the method has a potential value in determining the virulence of different strains of IBV by comparing their pathogenesis of chicken tissues in vitro."}
{"id": "PMID:206230", "title": "Purification of mengovirus by freon extraction and chromatography on protein-coated controlled pore glass.", "content": "Mengovirus, extracted from infected L-cell cultures with Freon 113 and concentrated from the aqueous phase with polyethyleneglycol, was chromatographed on protein-coated controlled pore glass (CPG). The covalent binding of protein to CPG is described. Further purification and concentration of mengovirus was achieved by isopycnic density gradient centrifugation in solutions of either CsCl or salts of iodinated benzoic acid derivatives. The described procedure is superior to conventional methods for the isolation and purification of large quantities of mengovirus. It yields highly purified virus preparations within a short time and a recovery of more than 50% of the starting infectivity.", "contents": "Purification of mengovirus by freon extraction and chromatography on protein-coated controlled pore glass. Mengovirus, extracted from infected L-cell cultures with Freon 113 and concentrated from the aqueous phase with polyethyleneglycol, was chromatographed on protein-coated controlled pore glass (CPG). The covalent binding of protein to CPG is described. Further purification and concentration of mengovirus was achieved by isopycnic density gradient centrifugation in solutions of either CsCl or salts of iodinated benzoic acid derivatives. The described procedure is superior to conventional methods for the isolation and purification of large quantities of mengovirus. It yields highly purified virus preparations within a short time and a recovery of more than 50% of the starting infectivity."}
{"id": "PMID:206232", "title": "Susceptibility of various FMDV strains to urea.", "content": "Resistance to urea in vitro at 37 degrees C varied for each FMDV strain analysed. The urea marker did not correlate with other markers such as resistance to acid, resistance to acidity or size of plaques under agar on BHK21/13 cells. The resistance to urea of subtypes A24 Cruzeiro, O1 Caseros and C3 Resende varied in accordance with their antigenic potency when administered to swine as a trivalent water-in-oil emulsion type vaccine.", "contents": "Susceptibility of various FMDV strains to urea. Resistance to urea in vitro at 37 degrees C varied for each FMDV strain analysed. The urea marker did not correlate with other markers such as resistance to acid, resistance to acidity or size of plaques under agar on BHK21/13 cells. The resistance to urea of subtypes A24 Cruzeiro, O1 Caseros and C3 Resende varied in accordance with their antigenic potency when administered to swine as a trivalent water-in-oil emulsion type vaccine."}
{"id": "PMID:206233", "title": "[Ultrastructural organization of the mammalian pineal body during postnatal ontogenesis].", "content": "Ultrastructural organization of the components composing the mammal pineal gland is analyzed on the basis of literature data and personal observations. Variations in the form, size and ultrastructural organization of the cellular elements in the pineal gland--pinealocytes, interstitial and glial cells--are discussed. The problem of dark and light pinealocytes is considered as a part of a general biological problem on the presence of dark and light cells as a reflection of the law on \"intermittent activity of functional structures\". An attention is paid to the organization of the microcirculatory bed and pericapillary space to the peculiarities of the secretory process in the organ. Dynamic changes in the cytologic organization of pinealocytes and other components of the organ in the postnatal ontogenesis are presented in detales.", "contents": "[Ultrastructural organization of the mammalian pineal body during postnatal ontogenesis]. Ultrastructural organization of the components composing the mammal pineal gland is analyzed on the basis of literature data and personal observations. Variations in the form, size and ultrastructural organization of the cellular elements in the pineal gland--pinealocytes, interstitial and glial cells--are discussed. The problem of dark and light pinealocytes is considered as a part of a general biological problem on the presence of dark and light cells as a reflection of the law on \"intermittent activity of functional structures\". An attention is paid to the organization of the microcirculatory bed and pericapillary space to the peculiarities of the secretory process in the organ. Dynamic changes in the cytologic organization of pinealocytes and other components of the organ in the postnatal ontogenesis are presented in detales."}
{"id": "PMID:206234", "title": "[Mechanism of formation of the psammoma bodies in serous adenocarcinomas of the ovaries].", "content": "Histological and electron microscopic examinations of 7 serous adenocarcinomas of the ovaries permitted to follow all the stages of psammous body formation starting from the submicroscopic level. The formation of psammous bodies was shown to be connected with a relatively differentiated epithelium of the adenocarcinomas. Initially, microcrystals of oxyapatites are deposed on accumulations of protein substances in ergastoplasm cysterns and on mitochondrial cristae. With further accumulation of these crystals relatively large intracytoplasmic inclusions of oxyapatites are formed which after confluence fill the cell which results in its death. In this way a small psammous body becomes free-lying.", "contents": "[Mechanism of formation of the psammoma bodies in serous adenocarcinomas of the ovaries]. Histological and electron microscopic examinations of 7 serous adenocarcinomas of the ovaries permitted to follow all the stages of psammous body formation starting from the submicroscopic level. The formation of psammous bodies was shown to be connected with a relatively differentiated epithelium of the adenocarcinomas. Initially, microcrystals of oxyapatites are deposed on accumulations of protein substances in ergastoplasm cysterns and on mitochondrial cristae. With further accumulation of these crystals relatively large intracytoplasmic inclusions of oxyapatites are formed which after confluence fill the cell which results in its death. In this way a small psammous body becomes free-lying."}
{"id": "PMID:206236", "title": "[Heterologous mesodermal tumor of the uterus of the chondrolipomyxosarcoma type].", "content": "A case of heterologous mesodermal tumor of the uterus of the chondrolipomyxosarcoma type in a woman of 70 is described. This observation was peculiar in that the tumor was benign for 25 years. Malignancy and extensive metastases into bones developed during the last year of life.", "contents": "[Heterologous mesodermal tumor of the uterus of the chondrolipomyxosarcoma type]. A case of heterologous mesodermal tumor of the uterus of the chondrolipomyxosarcoma type in a woman of 70 is described. This observation was peculiar in that the tumor was benign for 25 years. Malignancy and extensive metastases into bones developed during the last year of life."}
{"id": "PMID:206237", "title": "[Epithelioid sarcoma].", "content": "The analysis of data from literature and of the author's own 3 observations suggests that epithelioid sarcoma of Enzinger should be separated from soft tissue tumors of obscure genesis. It has a peculiar morphological structure, affects predominantly distal parts of the extremities in the area of tendons and joint capsules, and has some features of the clinical course and prognosis.", "contents": "[Epithelioid sarcoma]. The analysis of data from literature and of the author's own 3 observations suggests that epithelioid sarcoma of Enzinger should be separated from soft tissue tumors of obscure genesis. It has a peculiar morphological structure, affects predominantly distal parts of the extremities in the area of tendons and joint capsules, and has some features of the clinical course and prognosis."}
{"id": "PMID:206238", "title": "[Neural pathway of Powassan virus spread in the central nervous system of white mice].", "content": "Electron microscopic investigation of the brains and lumbar spinal cords of adult albino mice infected with Powassan virus was carried out. Virus particles were found within all parts of neurons (perikarya, dendrites, axon), as well as within synaptic apparatus and intercellular gaps of the central nervous tissue. The possibility of the virus spread both throughout the cytoplasm of nerve cells and their processes and the extracellular spaces of the brain was confirmed. Localization of virions within neurons, synapses and myelinated fibers of the spinal cord after intracerebral inoculation suggests that virus spread in the CNS can occur through the CNS parenchyma and also through the nervous conduction pathways. The possible mechanisms of virus dissemination in the CNS of albino mice with experimental Powassan virus encephalomyelitis are discussed.", "contents": "[Neural pathway of Powassan virus spread in the central nervous system of white mice]. Electron microscopic investigation of the brains and lumbar spinal cords of adult albino mice infected with Powassan virus was carried out. Virus particles were found within all parts of neurons (perikarya, dendrites, axon), as well as within synaptic apparatus and intercellular gaps of the central nervous tissue. The possibility of the virus spread both throughout the cytoplasm of nerve cells and their processes and the extracellular spaces of the brain was confirmed. Localization of virions within neurons, synapses and myelinated fibers of the spinal cord after intracerebral inoculation suggests that virus spread in the CNS can occur through the CNS parenchyma and also through the nervous conduction pathways. The possible mechanisms of virus dissemination in the CNS of albino mice with experimental Powassan virus encephalomyelitis are discussed."}
{"id": "PMID:206240", "title": "Bilateral retinal detachment following cytomegalovirus retinitis.", "content": "Bilateral retinal detachments developed in a renal allograft patient several months after the onset of cytomegalovirus retinitis. Laser photocoagulation was used to limit the posterior extent of one detachment until the detachment was surgically repaired. The thinned, atrophic retina that results from the necrotizing retinitis makes localization of retinal holes difficult and, in this case, contributed to the initial impression that these detachments were nonrhegmatogenous in origin.", "contents": "Bilateral retinal detachment following cytomegalovirus retinitis. Bilateral retinal detachments developed in a renal allograft patient several months after the onset of cytomegalovirus retinitis. Laser photocoagulation was used to limit the posterior extent of one detachment until the detachment was surgically repaired. The thinned, atrophic retina that results from the necrotizing retinitis makes localization of retinal holes difficult and, in this case, contributed to the initial impression that these detachments were nonrhegmatogenous in origin."}
{"id": "PMID:206241", "title": "Malignant fibrous histiocytoma of the maxillary sinus.", "content": "Malignant fibrous histiocytomas are an unusual neoplasm in the head and neck, and only six cases involving the maxillary sinus have been reported. The combination of an anaplastic storiform \"fibroblastic\" stroma with xanthomatous tumor giant cells histologically identifies this tumor. The high incidence of local recurrence of this neoplasm necessitates wide surgical resection. Regional lymph node and distant metastases, although not previously reported in maxillary sinus fibrous histiocytomas, occurred in this case.", "contents": "Malignant fibrous histiocytoma of the maxillary sinus. Malignant fibrous histiocytomas are an unusual neoplasm in the head and neck, and only six cases involving the maxillary sinus have been reported. The combination of an anaplastic storiform \"fibroblastic\" stroma with xanthomatous tumor giant cells histologically identifies this tumor. The high incidence of local recurrence of this neoplasm necessitates wide surgical resection. Regional lymph node and distant metastases, although not previously reported in maxillary sinus fibrous histiocytomas, occurred in this case."}
{"id": "PMID:206242", "title": "Recovery of eighth nerve function after cerebellopontine angle surgery.", "content": "Retrocochlear lesions cause typical patterns of hearing loss as detailed in special audiometric tests. Such losses, however, may be temporary deficits. Indeed, return to near normalcy following severely depressed auditory function is documented in this article. Conservative surgery on lesions influencing eighth nerve function should be considered. This is not to say that neoplasia can be partially removed, but rather that when tumors can be resected while preserving the cochlear nerve, this should be done inasmuch as good hearing levels may be restored.", "contents": "Recovery of eighth nerve function after cerebellopontine angle surgery. Retrocochlear lesions cause typical patterns of hearing loss as detailed in special audiometric tests. Such losses, however, may be temporary deficits. Indeed, return to near normalcy following severely depressed auditory function is documented in this article. Conservative surgery on lesions influencing eighth nerve function should be considered. This is not to say that neoplasia can be partially removed, but rather that when tumors can be resected while preserving the cochlear nerve, this should be done inasmuch as good hearing levels may be restored."}
{"id": "PMID:206243", "title": "Proliferation of cells and intracellular c-AMP content: comparative investigations of autologous lymphatic cells from palatine tonsils, nasopharyngeal tonsils, and blood.", "content": "The c-AMP content and thymidine incorporation were determined in tonsillogenic, adenoid, and peripheral lymphatic cells. A significant c-AMP decrease with simultaneous increase of the thymidine incorporation compared to the blood lymphocytes was noted in the tonsillogenic and adenoid cells. The negative regulative effect of c-AMP on cell proliferation and the function of tonsils at this processes are discussed.", "contents": "Proliferation of cells and intracellular c-AMP content: comparative investigations of autologous lymphatic cells from palatine tonsils, nasopharyngeal tonsils, and blood. The c-AMP content and thymidine incorporation were determined in tonsillogenic, adenoid, and peripheral lymphatic cells. A significant c-AMP decrease with simultaneous increase of the thymidine incorporation compared to the blood lymphocytes was noted in the tonsillogenic and adenoid cells. The negative regulative effect of c-AMP on cell proliferation and the function of tonsils at this processes are discussed."}
{"id": "PMID:206244", "title": "Effect of waterborne fluoride on fluoride concentration and solubility of dental enamel.", "content": "Enamel F level and depth of acid etch were measured in 166 teeth from 8 communities with water F ranging from .07-5.0 ppm. Enamel F decreased progressively from the surface inward and was positively correlated with water F. Depth of acid etch was inversely related to enamel F and water F. Relationships between water F, enamel F and enamel solubility were most consistent at water F levels up to 1.0-2.0 ppm.", "contents": "Effect of waterborne fluoride on fluoride concentration and solubility of dental enamel. Enamel F level and depth of acid etch were measured in 166 teeth from 8 communities with water F ranging from .07-5.0 ppm. Enamel F decreased progressively from the surface inward and was positively correlated with water F. Depth of acid etch was inversely related to enamel F and water F. Relationships between water F, enamel F and enamel solubility were most consistent at water F levels up to 1.0-2.0 ppm."}
{"id": "PMID:206248", "title": "An adenovirus survey of poultry flocks during the growing and laying periods.", "content": "Chicken adenoviruses were isolated from asymptomatic chickens on each of 7 farms tested; a majority of them induced cytopathology by the second serial passage. Although adenoviruses were isolated from chickens ranging in age from 8 to 34 weeks, the highest isolation rate was from those 8 to 14 weeks. Eight serotypes (1, 2, 4, 5, 6, 7, 8, and 9) were identified in a relatively small geographic area; serotypes 1, 4, 7, and 9 were isolated most frequently. Multiple serotypes were found on 6 of 7 farms, with 1 farm having 4 serotypes identified. Repeat isolations of the same serotypes were noted on 2 farms. The pattern of virus isolations was generally related to age but varied according to farm. Although new serotypes kept appearing, even after birds came into lay, no clinical problems were associated with them. The incidence of precipitin reactors tended to be low (10-40%) in immature birds but reached 80% or more after sexual maturity. The \"antiserum pool\" modification of the VN test was found to be accurate and less cumbersome than the conventional procedure for typing isolants.", "contents": "An adenovirus survey of poultry flocks during the growing and laying periods. Chicken adenoviruses were isolated from asymptomatic chickens on each of 7 farms tested; a majority of them induced cytopathology by the second serial passage. Although adenoviruses were isolated from chickens ranging in age from 8 to 34 weeks, the highest isolation rate was from those 8 to 14 weeks. Eight serotypes (1, 2, 4, 5, 6, 7, 8, and 9) were identified in a relatively small geographic area; serotypes 1, 4, 7, and 9 were isolated most frequently. Multiple serotypes were found on 6 of 7 farms, with 1 farm having 4 serotypes identified. Repeat isolations of the same serotypes were noted on 2 farms. The pattern of virus isolations was generally related to age but varied according to farm. Although new serotypes kept appearing, even after birds came into lay, no clinical problems were associated with them. The incidence of precipitin reactors tended to be low (10-40%) in immature birds but reached 80% or more after sexual maturity. The \"antiserum pool\" modification of the VN test was found to be accurate and less cumbersome than the conventional procedure for typing isolants."}
{"id": "PMID:206249", "title": "Studies of flocks with high mortality from lymphoid leukosis.", "content": "Two pairs of commercial white-egg parent flocks were selected for study, because one of each pair was observed to be dying with lymphoid leukosis at a high rate. The proportion of each flock producing eggs with lymphoid leukosis virus in the albumen was studied. In one pair the rate of birds shedding was no different in the high- and low-mortality flocks. The total rate of shedding was lower in the other pair, but the rate was higher in the high-mortality flock. These data indicate that the rate of virus infection is not always proportional to the development of lymphoid leukosis, and that other environmental factors may play a role. Direct complement-fixation tests on the albumens which were positive for lymphoid leukosis virus showed that group-specific antigen could be detected in 83%. Therefore, the direct complement-fixation test can be used on albumens as a rough estimate of shedding rate.", "contents": "Studies of flocks with high mortality from lymphoid leukosis. Two pairs of commercial white-egg parent flocks were selected for study, because one of each pair was observed to be dying with lymphoid leukosis at a high rate. The proportion of each flock producing eggs with lymphoid leukosis virus in the albumen was studied. In one pair the rate of birds shedding was no different in the high- and low-mortality flocks. The total rate of shedding was lower in the other pair, but the rate was higher in the high-mortality flock. These data indicate that the rate of virus infection is not always proportional to the development of lymphoid leukosis, and that other environmental factors may play a role. Direct complement-fixation tests on the albumens which were positive for lymphoid leukosis virus showed that group-specific antigen could be detected in 83%. Therefore, the direct complement-fixation test can be used on albumens as a rough estimate of shedding rate."}
{"id": "PMID:206247", "title": "Experimental infection of chickens with hemorrhagic enteritis virus.", "content": "Chickens were experimentally infected with hemorrhagic enteritis virus, causing lesions similar to those observed in turkeys. Lesions were induced by intraperitoneal and oral infection. Virus particles with the morphology of adenovirus were demonstrated in the spleens of infected chickens. Splenic extracts from infected chickens caused lesions of hemorrhagic enteritis in turkeys. Recovery from the infection in chickens was followed by the production of antibodies to HEV, demonstrated by agar-gel precipitin test.", "contents": "Experimental infection of chickens with hemorrhagic enteritis virus. Chickens were experimentally infected with hemorrhagic enteritis virus, causing lesions similar to those observed in turkeys. Lesions were induced by intraperitoneal and oral infection. Virus particles with the morphology of adenovirus were demonstrated in the spleens of infected chickens. Splenic extracts from infected chickens caused lesions of hemorrhagic enteritis in turkeys. Recovery from the infection in chickens was followed by the production of antibodies to HEV, demonstrated by agar-gel precipitin test."}
{"id": "PMID:206251", "title": "Serologic and pathogenicity studies of avian adenovirus isolated from chickens with inclusion body hepatitis.", "content": "A virus initially thought to be inclusion body hepatitis virus (IBHV), Tipton strain, was classified as an avian adenovirus (AAV) and shown to be antigenically related to 2 serotypes of AAV, 764 and YR36. The virus was antigenically unrelated to AAV serotype TR-22, which included IBHV, Tipton strain. Inoculating specific-pathogen-free chickens with the virus produced hepatitis with basophilic and eosinophilic staining intranuclear inclusion bodies.", "contents": "Serologic and pathogenicity studies of avian adenovirus isolated from chickens with inclusion body hepatitis. A virus initially thought to be inclusion body hepatitis virus (IBHV), Tipton strain, was classified as an avian adenovirus (AAV) and shown to be antigenically related to 2 serotypes of AAV, 764 and YR36. The virus was antigenically unrelated to AAV serotype TR-22, which included IBHV, Tipton strain. Inoculating specific-pathogen-free chickens with the virus produced hepatitis with basophilic and eosinophilic staining intranuclear inclusion bodies."}
{"id": "PMID:206252", "title": "Spontaneously occurring lymphoproliferative disease in ducks.", "content": "A naturally occurring lymphoproliferative disease was observed in a domestic flock of Muscovy ducks. Gross lesions were observed only in one of three ducks necropsied (in the small intestine). Microscopic lesions consisted of mononuclear cell infiltrates composed primarily of reticuloendothelial cells, mature lymphocytes, and plasma cells in livers, spleens, small intestines, peripheral nerves, and brains. Antibodies to reticuloendotheliosis virus were detected in sera of four ducks, whereas all six ducks examined lacked antibodies ot Marek's disease virus.", "contents": "Spontaneously occurring lymphoproliferative disease in ducks. A naturally occurring lymphoproliferative disease was observed in a domestic flock of Muscovy ducks. Gross lesions were observed only in one of three ducks necropsied (in the small intestine). Microscopic lesions consisted of mononuclear cell infiltrates composed primarily of reticuloendothelial cells, mature lymphocytes, and plasma cells in livers, spleens, small intestines, peripheral nerves, and brains. Antibodies to reticuloendotheliosis virus were detected in sera of four ducks, whereas all six ducks examined lacked antibodies ot Marek's disease virus."}
{"id": "PMID:206253", "title": "A clinical evaluation of chickens inoculated with several avian adenovirus isolants.", "content": "Clinical-chemistry values were determined in young specific-pathogen-free single-comb White Leghorn chickens, both uninoculated and inoculated intra-abdominally at one day old with one of several avian adenovirus isolants. Clinical values for plasma proteins and enzymes indicative of liver function were determined at 3, 7, 10, 14, and 21 days postinoculation. Plasma glutamic oxalacetic transaminase and glutamic pyruvic transaminase activities were elevated in the virus-inoculated birds, along with decreased  albumin levels suggesting liver necrosis, Subsequent histopathologic evaluations confirmed hepatic necrosis in the virus-inoculated groups, demonstrating the potential value of clinical-chemistry assay techniques for diagnosing subclinical disease associated with avian adenoviruses.", "contents": "A clinical evaluation of chickens inoculated with several avian adenovirus isolants. Clinical-chemistry values were determined in young specific-pathogen-free single-comb White Leghorn chickens, both uninoculated and inoculated intra-abdominally at one day old with one of several avian adenovirus isolants. Clinical values for plasma proteins and enzymes indicative of liver function were determined at 3, 7, 10, 14, and 21 days postinoculation. Plasma glutamic oxalacetic transaminase and glutamic pyruvic transaminase activities were elevated in the virus-inoculated birds, along with decreased  albumin levels suggesting liver necrosis, Subsequent histopathologic evaluations confirmed hepatic necrosis in the virus-inoculated groups, demonstrating the potential value of clinical-chemistry assay techniques for diagnosing subclinical disease associated with avian adenoviruses."}
{"id": "PMID:206250", "title": "An improved method for extracting cell-free herpesviruses of Marek's disease and turkeys from infected cell cultures.", "content": "Sonic extraction of cell-free Marek's disease herpesvirus (MDHV) and turkey herpesvirus (HVT) from infected cell cultures was improved by incorporating sorbitol in the suspending media. Yields of cell-free virus of virulent MDHV were significantly increased with 10% sorbitol added to SPGA-EDTA buffer. Avirulent strains of MDHV and HVT were respectively readily extracted with SPGA-EDTA and SPGA as the suspending medium, and extraction of their cell-free viruses was moderately improved by adding sorbitol to the suspending medium.", "contents": "An improved method for extracting cell-free herpesviruses of Marek's disease and turkeys from infected cell cultures. Sonic extraction of cell-free Marek's disease herpesvirus (MDHV) and turkey herpesvirus (HVT) from infected cell cultures was improved by incorporating sorbitol in the suspending media. Yields of cell-free virus of virulent MDHV were significantly increased with 10% sorbitol added to SPGA-EDTA buffer. Avirulent strains of MDHV and HVT were respectively readily extracted with SPGA-EDTA and SPGA as the suspending medium, and extraction of their cell-free viruses was moderately improved by adding sorbitol to the suspending medium."}
{"id": "PMID:206258", "title": "Malate dehydrogenase of the cytosol. Preparation and reduced nicotinamide-adenine dinucleotide-binding studies.", "content": "1. Two methods of preparing pig heart soluble malate dehydrogenase are described. A slow method yields an enzyme composed of three electrophoretically separable subforms. The more rapid method reproducibly gives a high yield of an enzyme that consists predominantly of the least acid subform. 2. The A(1%) (1cm) of the protein was redetermined as 15 at 280nm. By using this value the enzyme molecule was found to contain two independent and indistinguishable NADH-binding sites in titrations with NADH. 3. No evidence was found for the dissociation of the enzyme in the concentration range 0.02-7.2mum. 4. l-Malate (0.1m) tightened the binding of NADH to both pig and ox heart enzyme (2-fold), but, in contrast with the report by Mueggler, Dahlquist & Wolfe [(1975) Biochemistry14, 3490-3497], did not cause co-operative interactions between the binding sites. 5. Fructose 1,6-bisphosphate had no effect on the binding of NADH to the pig heart enzyme, but with the ox heart enzyme the NADH is slowly oxidized. This slow oxidation explains the ;sigmoidal' binding curves obtained when NADH was added to ox heart soluble malate dehydrogenase in the presence of fructose 1,6-bisphosphate [Cassman (1973) Biochem. Biophys. Res. Commun.53, 666-672] without the postulate of site-site interactions. 6. It is concluded that neither l-malate nor fructose 1,6-bisphosphate could in vivo modulate the activity of soluble malate dehydrogenase and alter the rates of transport of NADH between the cytosol and the mitochondrion. 7. Details of the preparation of soluble malate dehydrogenase have been deposited as Supplementary Publication SUP 50080 (8 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained under the terms given in Biochem. J. (1978) 169, 5.", "contents": "Malate dehydrogenase of the cytosol. Preparation and reduced nicotinamide-adenine dinucleotide-binding studies. 1. Two methods of preparing pig heart soluble malate dehydrogenase are described. A slow method yields an enzyme composed of three electrophoretically separable subforms. The more rapid method reproducibly gives a high yield of an enzyme that consists predominantly of the least acid subform. 2. The A(1%) (1cm) of the protein was redetermined as 15 at 280nm. By using this value the enzyme molecule was found to contain two independent and indistinguishable NADH-binding sites in titrations with NADH. 3. No evidence was found for the dissociation of the enzyme in the concentration range 0.02-7.2mum. 4. l-Malate (0.1m) tightened the binding of NADH to both pig and ox heart enzyme (2-fold), but, in contrast with the report by Mueggler, Dahlquist & Wolfe [(1975) Biochemistry14, 3490-3497], did not cause co-operative interactions between the binding sites. 5. Fructose 1,6-bisphosphate had no effect on the binding of NADH to the pig heart enzyme, but with the ox heart enzyme the NADH is slowly oxidized. This slow oxidation explains the ;sigmoidal' binding curves obtained when NADH was added to ox heart soluble malate dehydrogenase in the presence of fructose 1,6-bisphosphate [Cassman (1973) Biochem. Biophys. Res. Commun.53, 666-672] without the postulate of site-site interactions. 6. It is concluded that neither l-malate nor fructose 1,6-bisphosphate could in vivo modulate the activity of soluble malate dehydrogenase and alter the rates of transport of NADH between the cytosol and the mitochondrion. 7. Details of the preparation of soluble malate dehydrogenase have been deposited as Supplementary Publication SUP 50080 (8 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained under the terms given in Biochem. J. (1978) 169, 5."}
{"id": "PMID:206259", "title": "Purification and properties of the S1 secondary alkylsulphohydrolase of the detergent-degrading micro-organism, Pseudomonas C12B.", "content": "The S1 secondary alkylsulphohydrolase of the detergent-degrading micro-organism, Pseudomonas C12B, was separated from other alkylsulphohydrolases and purified to homogeneity. Under the experimental conditions used the enzyme completely hydrolysed d-octan-2-yl sulphate (d-1-methylheptyl sulphate), but showed no activity towards the corresponding l-isomer. Additional evidence has been obtained to indicate that it is probably optically stereospecific for d-secondary alkyl sulphate esters with the ester sulphate group at C-2 and with a chain length of at least seven carbon atoms. Enzyme activity towards racemic samples of heptan-2-yl sulphate (1-methylhexyl sulphate), octan-2-yl sulphate and decan-2-yl sulphate (1-methylnonyl sulphate) increased with increasing chain length. l-Octan-2-yl sulphate is a competitive inhibitor of the enzyme, as are certain primary alkyl sulphates and primary alkanesulphonates. Inhibition by each of the last two types of compounds is characteristic of the behaviour of an homologous series. Inhibition increases with increasing chain length and plots of log K(i) values against the number of carbon atoms in each alkyl chain show the expected linear relationship. A crude preparation of the S2 secondary alkylsulphohydrolase was used to show that this particular enzyme hydrolyses l-octan-2-yl sulphate, but is probably inactive towards the corresponding d-isomer. The similarity of the S1 and S2 enzymes to the CS2 and CS1 enzymes respectively of Comamonas terrigena was established, and some comments have been made on the possible roles of these and other alkylsulphohydrolases in the biodegradation of detergents.", "contents": "Purification and properties of the S1 secondary alkylsulphohydrolase of the detergent-degrading micro-organism, Pseudomonas C12B. The S1 secondary alkylsulphohydrolase of the detergent-degrading micro-organism, Pseudomonas C12B, was separated from other alkylsulphohydrolases and purified to homogeneity. Under the experimental conditions used the enzyme completely hydrolysed d-octan-2-yl sulphate (d-1-methylheptyl sulphate), but showed no activity towards the corresponding l-isomer. Additional evidence has been obtained to indicate that it is probably optically stereospecific for d-secondary alkyl sulphate esters with the ester sulphate group at C-2 and with a chain length of at least seven carbon atoms. Enzyme activity towards racemic samples of heptan-2-yl sulphate (1-methylhexyl sulphate), octan-2-yl sulphate and decan-2-yl sulphate (1-methylnonyl sulphate) increased with increasing chain length. l-Octan-2-yl sulphate is a competitive inhibitor of the enzyme, as are certain primary alkyl sulphates and primary alkanesulphonates. Inhibition by each of the last two types of compounds is characteristic of the behaviour of an homologous series. Inhibition increases with increasing chain length and plots of log K(i) values against the number of carbon atoms in each alkyl chain show the expected linear relationship. A crude preparation of the S2 secondary alkylsulphohydrolase was used to show that this particular enzyme hydrolyses l-octan-2-yl sulphate, but is probably inactive towards the corresponding d-isomer. The similarity of the S1 and S2 enzymes to the CS2 and CS1 enzymes respectively of Comamonas terrigena was established, and some comments have been made on the possible roles of these and other alkylsulphohydrolases in the biodegradation of detergents."}
{"id": "PMID:206260", "title": "Comparison of guinea-pig serum lipoproteins after iodination by two different methods.", "content": "1. Guinea-pig low-density lipoproteins were isolated by ultracentrifugation and iodinated either by the IC1 method or by the chloramine-T procedure. 2. The efficiency of labelling by both methods was essentially the same. 3. When the two products were compared by ultracentrifugation, gel chromatography and immunodiffusion analysis, no significant difference in their properties was detected. 4. When they were compared by gradient-gel electrophoresis, aggregates were found in the product of the IC1 method, but not in the lipoprotein iodinated by the chloramine-T process. 5. Both products were metabolized by the guinea pig with essentially the same fractional catabolic rate. 6. The fractional catabolic rate of lipoprotein iodinated by the chloramine-T method was not significantly different from that of lipoprotein biologically labelled in the protein moiety with [75Se]selenomethionine. 7. It is concluded that the products of both methods of iodination are almost equally acceptable, provided that the optimum conditions for the chloramine-T reaction are carefully established.", "contents": "Comparison of guinea-pig serum lipoproteins after iodination by two different methods. 1. Guinea-pig low-density lipoproteins were isolated by ultracentrifugation and iodinated either by the IC1 method or by the chloramine-T procedure. 2. The efficiency of labelling by both methods was essentially the same. 3. When the two products were compared by ultracentrifugation, gel chromatography and immunodiffusion analysis, no significant difference in their properties was detected. 4. When they were compared by gradient-gel electrophoresis, aggregates were found in the product of the IC1 method, but not in the lipoprotein iodinated by the chloramine-T process. 5. Both products were metabolized by the guinea pig with essentially the same fractional catabolic rate. 6. The fractional catabolic rate of lipoprotein iodinated by the chloramine-T method was not significantly different from that of lipoprotein biologically labelled in the protein moiety with [75Se]selenomethionine. 7. It is concluded that the products of both methods of iodination are almost equally acceptable, provided that the optimum conditions for the chloramine-T reaction are carefully established."}
{"id": "PMID:206261", "title": "Differential activation of type-I and type-II adenosine 3':5'-cyclic monophosphate-dependent protein kinases in liver of glucagon-treated rats.", "content": "The protein-bound cyclic AMP and the activity of cytosolic protein kinases in the presence and absence of cyclic AMP were determined in rat liver up to 2h after injection of glucagon. On the basis of the different salt-sensitivities of the activated cyclic AMP-dependent proteinkinases I and II, an activation of protein kinase II restricted to the high cyclic AMP concentrations present in the first 30 min after hormone injection was found. Essentially the same result was obtained by chromatographic analysis on DEAE-cellulose of liver cytosol from untreated rats and from rats killed at 2 and 60 min after glucagon injection. Protein kinase II activation was only detected at 2 min after injection. In contrast, the cyclic AMP-dependent protein kinase I was found to be nearly totally activated at 2 min and to be still almost as active at 60 min after the hormone stimulus, whereas the amount of bound cyclic AMP and the activation of total cytosolic protein kinases had fallen to two-thirds of their maximal values during this time period. A third cyclic AMP-independent protein kinase, which co-chromatographed with protein kinase type II, could be clearly distinguished from the two cyclic AMP-dependent kinases by use of the heat-stable inhibitor from bovine muscle, which totally inhibited the cyclic AMP-dependent enzymes, but stimulated the cyclic AMP-independent protein kinase.", "contents": "Differential activation of type-I and type-II adenosine 3':5'-cyclic monophosphate-dependent protein kinases in liver of glucagon-treated rats. The protein-bound cyclic AMP and the activity of cytosolic protein kinases in the presence and absence of cyclic AMP were determined in rat liver up to 2h after injection of glucagon. On the basis of the different salt-sensitivities of the activated cyclic AMP-dependent proteinkinases I and II, an activation of protein kinase II restricted to the high cyclic AMP concentrations present in the first 30 min after hormone injection was found. Essentially the same result was obtained by chromatographic analysis on DEAE-cellulose of liver cytosol from untreated rats and from rats killed at 2 and 60 min after glucagon injection. Protein kinase II activation was only detected at 2 min after injection. In contrast, the cyclic AMP-dependent protein kinase I was found to be nearly totally activated at 2 min and to be still almost as active at 60 min after the hormone stimulus, whereas the amount of bound cyclic AMP and the activation of total cytosolic protein kinases had fallen to two-thirds of their maximal values during this time period. A third cyclic AMP-independent protein kinase, which co-chromatographed with protein kinase type II, could be clearly distinguished from the two cyclic AMP-dependent kinases by use of the heat-stable inhibitor from bovine muscle, which totally inhibited the cyclic AMP-dependent enzymes, but stimulated the cyclic AMP-independent protein kinase."}
{"id": "PMID:206255", "title": "Typing field isolates of infectious bronchitis by the plaque-reduction test.", "content": "A technique is described for typing field isolates of infectious bronchitis virus by plaque-reduction assay of the serum antibody response of chickens experimentally infected with such isolates. Also reported are use of the technique with field isolates and a comparison of results obtained in plaque-reduction assay and in tracheal-ring organ-culture assay.", "contents": "Typing field isolates of infectious bronchitis by the plaque-reduction test. A technique is described for typing field isolates of infectious bronchitis virus by plaque-reduction assay of the serum antibody response of chickens experimentally infected with such isolates. Also reported are use of the technique with field isolates and a comparison of results obtained in plaque-reduction assay and in tracheal-ring organ-culture assay."}
{"id": "PMID:206262", "title": "Comparative studies on the 25-hydroxylations of cholecalciferol and 1 alpha-hydroxycholecalfierol in perfused rat liver.", "content": "The 25-hydroxylations of [(3)H]cholecalciferol and 1alpha-hydroxy[(3)H]cholecalciferol in perfused rat liver were compared. Results showed that about twice as much 1alpha(OH)D(3) (1alpha-hydroxycholecalciferol) was incorporated into the liver as cholecalciferol. 25-Hydroxy[(3)H]cholecalciferol and 1alpha-25-dihydroxy[(3)H]cholecalciferol were not incorporated significantly. Livers isolated from vitamin D-deficient rats formed the 25-hydroxy derivatives of cholecalciferol and 1alpha(OH)D(3) respectively linearly with time for at least 120min. The rate of 1alpha,25(OH)(2)D(3) (1alpha,25-dihydroxycholecalciferol) production increased exactly 10-fold on successive 10-fold increases in the dose of 1alpha(OH)D(3), suggesting that hepatic 25-hydroxylation of 1alpha(OH)D(3) is not under metabolic control. On the other hand, the rate of conversion of cholecalciferol into 25(OH)D(3) (25-hydroxycholecalciferol) did not increase linearly with increase in the amount of cholecalciferol in the perfusate. The 25-hydroxylation of cholecalciferol seemed to proceed at a similar rate to that of 1alpha(OH)D(3) at doses of less than 1nmol, but with doses of more than 2.5nmol, the conversion of cholecalciferol into 25(OH)D(3) became much less efficient, though the linear relation between the amounts of substrate and product was maintained. A reciprocal plot of data on the 25-hydroxylation of cholecalciferol gave two K(m) values of about 5.6nm and 1.0mum, whereas that for the 25-hydroxylation of 1alpha(OH)D(3) gave a single K(m) value of about 2.0mum. These results suggest that there are two modes of 25-hydroxylation of cholecalciferol in the liver, which seem to be closely related to the mechanism of control of 25(OH)D(3) production by the liver.", "contents": "Comparative studies on the 25-hydroxylations of cholecalciferol and 1 alpha-hydroxycholecalfierol in perfused rat liver. The 25-hydroxylations of [(3)H]cholecalciferol and 1alpha-hydroxy[(3)H]cholecalciferol in perfused rat liver were compared. Results showed that about twice as much 1alpha(OH)D(3) (1alpha-hydroxycholecalciferol) was incorporated into the liver as cholecalciferol. 25-Hydroxy[(3)H]cholecalciferol and 1alpha-25-dihydroxy[(3)H]cholecalciferol were not incorporated significantly. Livers isolated from vitamin D-deficient rats formed the 25-hydroxy derivatives of cholecalciferol and 1alpha(OH)D(3) respectively linearly with time for at least 120min. The rate of 1alpha,25(OH)(2)D(3) (1alpha,25-dihydroxycholecalciferol) production increased exactly 10-fold on successive 10-fold increases in the dose of 1alpha(OH)D(3), suggesting that hepatic 25-hydroxylation of 1alpha(OH)D(3) is not under metabolic control. On the other hand, the rate of conversion of cholecalciferol into 25(OH)D(3) (25-hydroxycholecalciferol) did not increase linearly with increase in the amount of cholecalciferol in the perfusate. The 25-hydroxylation of cholecalciferol seemed to proceed at a similar rate to that of 1alpha(OH)D(3) at doses of less than 1nmol, but with doses of more than 2.5nmol, the conversion of cholecalciferol into 25(OH)D(3) became much less efficient, though the linear relation between the amounts of substrate and product was maintained. A reciprocal plot of data on the 25-hydroxylation of cholecalciferol gave two K(m) values of about 5.6nm and 1.0mum, whereas that for the 25-hydroxylation of 1alpha(OH)D(3) gave a single K(m) value of about 2.0mum. These results suggest that there are two modes of 25-hydroxylation of cholecalciferol in the liver, which seem to be closely related to the mechanism of control of 25(OH)D(3) production by the liver."}
{"id": "PMID:206256", "title": "Response to several avian respiratory viruses as affected by infectious bursal disease virus.", "content": "After being inoculated with the infectious bursal disease virus (IBDV) at one day of age, specific-pathogen-free chickens were inoculated with either Newcastle disease virus (NDV), infectious bronchitis virus (IBV), or infectious laryngotracheitis virus (ILTV). Their immunity was challenged 2-3 weeks later with homologous virus, and antibody titers were determined for ILTV and IBV. Several studies were made to determine the effects of IBDV on the development of persistent or chronic virus infections. Chickens susceptible to IBDV were exposed to IBDV at one day and inoculated at two weeks of age with either NDV, IBV, or ILTV. Two, three, four, and five weeks postinoculation with the respiratory viruses, tracheal swabbings were collected for virus isolations. The birds were challenged with homologous virus at five weeks postinoculation. The results show that early (1-day) infections with IBDV affect the response of young birds to several avian respiratory viruses, as indicated by lowered resistance to challenge and humoral antibody levels for birds inoculated with ILTV and NDV. Birds infected with IBV and IBDV withstood IBV challenge but were much more prone to persistent infections than were birds not exposed to IBDV. High death rates and decreased weights in all IBDV-inoculated groups demonstrated the damaging effects of early IBDV infection.", "contents": "Response to several avian respiratory viruses as affected by infectious bursal disease virus. After being inoculated with the infectious bursal disease virus (IBDV) at one day of age, specific-pathogen-free chickens were inoculated with either Newcastle disease virus (NDV), infectious bronchitis virus (IBV), or infectious laryngotracheitis virus (ILTV). Their immunity was challenged 2-3 weeks later with homologous virus, and antibody titers were determined for ILTV and IBV. Several studies were made to determine the effects of IBDV on the development of persistent or chronic virus infections. Chickens susceptible to IBDV were exposed to IBDV at one day and inoculated at two weeks of age with either NDV, IBV, or ILTV. Two, three, four, and five weeks postinoculation with the respiratory viruses, tracheal swabbings were collected for virus isolations. The birds were challenged with homologous virus at five weeks postinoculation. The results show that early (1-day) infections with IBDV affect the response of young birds to several avian respiratory viruses, as indicated by lowered resistance to challenge and humoral antibody levels for birds inoculated with ILTV and NDV. Birds infected with IBV and IBDV withstood IBV challenge but were much more prone to persistent infections than were birds not exposed to IBDV. High death rates and decreased weights in all IBDV-inoculated groups demonstrated the damaging effects of early IBDV infection."}
{"id": "PMID:206263", "title": "Calcium metabolism in rat hepatocytes.", "content": "1. The total calcium concentration in rat hepatocytes was 7.9 microgram-atoms/g dry wt.; 77% of this was mitochondrial. Approx. 20% of cell calcium exchanged with 45Ca within 2 min. Thereafter incorporation proceeded at a low rate to reach 28% of total calcium after 60 min. Incorporation into mitochondria showed a similar time course and accounted for 20% of mitochondrial total calcium after 60 min. 2. The alpha-adrenergic agonists phenylephrine and adrenaline + propranolol stimulated incorporation of 45Ca into hepatocytes. Phenylephrine was shown to increase total calcium in hepatocytes. Phenylephrine inhibited efflux fo 45Ca from hepatocytes perifused with calcium-free medium. 3. Glucagon, dibutryl cyclic AMP and beta-adrenergic agonists adrenaline and 3-isobutyl-1-methyl-xanthine stimulated calcium efflux from hepatocytes perifused with calcium-free medium. The effect of glucagon was blocked by insulin. Insulin itself had no effect on calcium efflux and it did not affect the response to dibutyryl cyclic AMP. 4. Incorporation of 45Ca into mitochondria in hepatocytes was stimulated by phenylephrine and inhibited by glucagon and by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. The effect of glucagon was blocked by insulin. 5. Ionophore A23187 stimulated hepatocyte uptake of 45Ca, uptake of 45Ca into mitochondria in hepatocytes and efflux of 45Ca into a calcium-free medium.", "contents": "Calcium metabolism in rat hepatocytes. 1. The total calcium concentration in rat hepatocytes was 7.9 microgram-atoms/g dry wt.; 77% of this was mitochondrial. Approx. 20% of cell calcium exchanged with 45Ca within 2 min. Thereafter incorporation proceeded at a low rate to reach 28% of total calcium after 60 min. Incorporation into mitochondria showed a similar time course and accounted for 20% of mitochondrial total calcium after 60 min. 2. The alpha-adrenergic agonists phenylephrine and adrenaline + propranolol stimulated incorporation of 45Ca into hepatocytes. Phenylephrine was shown to increase total calcium in hepatocytes. Phenylephrine inhibited efflux fo 45Ca from hepatocytes perifused with calcium-free medium. 3. Glucagon, dibutryl cyclic AMP and beta-adrenergic agonists adrenaline and 3-isobutyl-1-methyl-xanthine stimulated calcium efflux from hepatocytes perifused with calcium-free medium. The effect of glucagon was blocked by insulin. Insulin itself had no effect on calcium efflux and it did not affect the response to dibutyryl cyclic AMP. 4. Incorporation of 45Ca into mitochondria in hepatocytes was stimulated by phenylephrine and inhibited by glucagon and by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. The effect of glucagon was blocked by insulin. 5. Ionophore A23187 stimulated hepatocyte uptake of 45Ca, uptake of 45Ca into mitochondria in hepatocytes and efflux of 45Ca into a calcium-free medium."}
{"id": "PMID:206264", "title": "Reaction of formiminoglutamate with liver glutamate dehydrogenase.", "content": "1. Kinetic aspects of the reaction between crystalline bovine liver glutamate dehydrogenase and formiminoglutamate were investigated to establish the conditions under which the latter may interfere with the assay of glutamate by using glutamate dehydrogenase and to explain why formiminoglutamate accumulates in vivo after histidine loading, although it can react with glutamate dehydrogenase. The Km and Vmax. values were compared with those of the enzyme reacting with glutamate. At pH 7.4 Km for formiminoglutamate was much higher and Vmax. much lower than the values for glutamate. 2. The equilibrium constant at pH 7.0 was 0.017 micrometer with formiminoglutamate, i.e. about one two-hundredths that with glutamate. 3. In vivo the interaction between glutamate dehydrogenase and formiminoglutamate is minimal even when the concentration of the latter in the liver is greatly raised, as in cobalamine or folate deficiency after histidine loading. 4. At pH 9.3, i.e. under the conditions for the assay of glutamate by glutamate dehydrogenase, formiminoglutamate reacts readily with the enzyme.", "contents": "Reaction of formiminoglutamate with liver glutamate dehydrogenase. 1. Kinetic aspects of the reaction between crystalline bovine liver glutamate dehydrogenase and formiminoglutamate were investigated to establish the conditions under which the latter may interfere with the assay of glutamate by using glutamate dehydrogenase and to explain why formiminoglutamate accumulates in vivo after histidine loading, although it can react with glutamate dehydrogenase. The Km and Vmax. values were compared with those of the enzyme reacting with glutamate. At pH 7.4 Km for formiminoglutamate was much higher and Vmax. much lower than the values for glutamate. 2. The equilibrium constant at pH 7.0 was 0.017 micrometer with formiminoglutamate, i.e. about one two-hundredths that with glutamate. 3. In vivo the interaction between glutamate dehydrogenase and formiminoglutamate is minimal even when the concentration of the latter in the liver is greatly raised, as in cobalamine or folate deficiency after histidine loading. 4. At pH 9.3, i.e. under the conditions for the assay of glutamate by glutamate dehydrogenase, formiminoglutamate reacts readily with the enzyme."}
{"id": "PMID:206265", "title": "Cyclic AMP-dependent histone-specific nucleoplasmic protein kinase from rat liver.", "content": "A nucleoplasmic histone kinase activity was isolated from livers of adult rats and purified 39-fold compared with whole nuclei by ultracentrifugation of the nuclear extract and Sephadex G-200 gel filtration in the presence of cyclic AMP. Analysis by polyacrylamide-gel electrophoresis as well as by gel filtration indicates a mol.wt. of approx. 60,000 for the catalytic subunit and 130000-150000 for the cyclic AMP-binding activity. The purified enzyme displays a 20-fold greater preference for histone fractions 1 and 2b than for any non-histone substrate, including alpha-casein. Endogenous protein in the preparation is not appreciably phosphorylated. The unfractioned enzyme is stimulated significantly by cyclic GMP, cyclic IMP and dibutyryl cyclic AMP as well as by cyclic AMP. The catalytic reaction requires Mg2+ (Km 1.9mM) and ATP (Km 15.4 micron). Half-maximal activity of the enzyme is observed with histone 2b at 12micron and histone 1 at a higher substrate concentration. The pH optima are 6.1 and 6.5 with histones 2b and 1 respectively. This nuclear protein kinase appears to be distinct from other nuclear enzymes that have been reported, on the basis of histone specificity, univalent-salt-sensitivity, pH optima and nuclear location. However, the enzyme possesses many properties similar to those of the cytoplasmic kinases, including cyclic AMP-dependence, Mg2+ and ATP affinities and pH optima. It differs from cytoplasmic protein kinase type I, the major form in the liver, with respect to bivalent-cation effects and response to the heat-stable protein kinase inhibitor protein isolated from ox heart.", "contents": "Cyclic AMP-dependent histone-specific nucleoplasmic protein kinase from rat liver. A nucleoplasmic histone kinase activity was isolated from livers of adult rats and purified 39-fold compared with whole nuclei by ultracentrifugation of the nuclear extract and Sephadex G-200 gel filtration in the presence of cyclic AMP. Analysis by polyacrylamide-gel electrophoresis as well as by gel filtration indicates a mol.wt. of approx. 60,000 for the catalytic subunit and 130000-150000 for the cyclic AMP-binding activity. The purified enzyme displays a 20-fold greater preference for histone fractions 1 and 2b than for any non-histone substrate, including alpha-casein. Endogenous protein in the preparation is not appreciably phosphorylated. The unfractioned enzyme is stimulated significantly by cyclic GMP, cyclic IMP and dibutyryl cyclic AMP as well as by cyclic AMP. The catalytic reaction requires Mg2+ (Km 1.9mM) and ATP (Km 15.4 micron). Half-maximal activity of the enzyme is observed with histone 2b at 12micron and histone 1 at a higher substrate concentration. The pH optima are 6.1 and 6.5 with histones 2b and 1 respectively. This nuclear protein kinase appears to be distinct from other nuclear enzymes that have been reported, on the basis of histone specificity, univalent-salt-sensitivity, pH optima and nuclear location. However, the enzyme possesses many properties similar to those of the cytoplasmic kinases, including cyclic AMP-dependence, Mg2+ and ATP affinities and pH optima. It differs from cytoplasmic protein kinase type I, the major form in the liver, with respect to bivalent-cation effects and response to the heat-stable protein kinase inhibitor protein isolated from ox heart."}
{"id": "PMID:206266", "title": "Problems encountered in measuring the activity of phosphatidate phosphohydrolase.", "content": "The measurement of phosphate release from phosphatidate overestimates the microsomal activity of phosphatidate phosphohydrolase from rat liver, since phosphate is also produced via the glycerol phosphate that results from the deacylation of phosphatidate. The determination of phosphate production can be a reliable assay for the soluble phosphatidate phosphohydrolase in rat liver, because the glycerol phosphate formed is not hydrolysed under the conditions used.", "contents": "Problems encountered in measuring the activity of phosphatidate phosphohydrolase. The measurement of phosphate release from phosphatidate overestimates the microsomal activity of phosphatidate phosphohydrolase from rat liver, since phosphate is also produced via the glycerol phosphate that results from the deacylation of phosphatidate. The determination of phosphate production can be a reliable assay for the soluble phosphatidate phosphohydrolase in rat liver, because the glycerol phosphate formed is not hydrolysed under the conditions used."}
{"id": "PMID:206267", "title": "Stopped-flow spectrophotometric studies on the reaction of turkey liver xanthine dehydrogenase with reducing substrates.", "content": "The kinetics of reduction of turkey liver xanthine dehydrogenase by substrates were investigated by stopped-flow spectrophotometry. The results may be explained in terms of the known redox potentials of the various centres in the enzyme [Barber, Bray, Cammack & Coughlan (1977) Biochem. J. 163, 279-289]. They are, morover, consistent with the scheme [Olson, Ballou, Palmer & Massey (1974) J. Biol. Chem. 249, 4363-4382] in which reduction occurs in three consecutive steps, one molecule of substrate reacting with the active site at each step. First-order rate constants believed to correspond respectively to the combined first and second steps and to the third step in the reduction by excess of xanthine and of NADH were determined. The rates of reaction with these substrates in the combined first and second steps are independent of the degree of enzyme functionality.", "contents": "Stopped-flow spectrophotometric studies on the reaction of turkey liver xanthine dehydrogenase with reducing substrates. The kinetics of reduction of turkey liver xanthine dehydrogenase by substrates were investigated by stopped-flow spectrophotometry. The results may be explained in terms of the known redox potentials of the various centres in the enzyme [Barber, Bray, Cammack & Coughlan (1977) Biochem. J. 163, 279-289]. They are, morover, consistent with the scheme [Olson, Ballou, Palmer & Massey (1974) J. Biol. Chem. 249, 4363-4382] in which reduction occurs in three consecutive steps, one molecule of substrate reacting with the active site at each step. First-order rate constants believed to correspond respectively to the combined first and second steps and to the third step in the reduction by excess of xanthine and of NADH were determined. The rates of reaction with these substrates in the combined first and second steps are independent of the degree of enzyme functionality."}
{"id": "PMID:206268", "title": "Filtration of chylomicrons by the liver may influence cholesterol metabolism and atherosclerosis.", "content": "A fenestrated endothelial lining of sinusoids in rat liver has been shown to separate chylomicrons of different sizes following their injection into the portal vein. This sieving may have physiological importance, since during low dietary fat intake some intestinal lipoproteins are probably small enough to contact liver cells, but during high dietary fat loads most chylomicrons are too large to pass through the filter and must first be degraded to smaller remnants. The liver plays a central role in cholesterol metabolism since it catabolises dietary cholesterol which inhibits synthesis of cholesterol to be circulated as liver-derived very low density lipoproteins (VLDL) and low density lipoproteins. The sieving of chylomicrons, remnants and other lipoproteins by the sinusoidal endothelium of the liver may thus play an important role in lipid transport, affecting the balance of various lipoprotein moieties which in turn may affect the relationship of dietary lipids to various hyperlipidaemias and atherosclerosis.", "contents": "Filtration of chylomicrons by the liver may influence cholesterol metabolism and atherosclerosis. A fenestrated endothelial lining of sinusoids in rat liver has been shown to separate chylomicrons of different sizes following their injection into the portal vein. This sieving may have physiological importance, since during low dietary fat intake some intestinal lipoproteins are probably small enough to contact liver cells, but during high dietary fat loads most chylomicrons are too large to pass through the filter and must first be degraded to smaller remnants. The liver plays a central role in cholesterol metabolism since it catabolises dietary cholesterol which inhibits synthesis of cholesterol to be circulated as liver-derived very low density lipoproteins (VLDL) and low density lipoproteins. The sieving of chylomicrons, remnants and other lipoproteins by the sinusoidal endothelium of the liver may thus play an important role in lipid transport, affecting the balance of various lipoprotein moieties which in turn may affect the relationship of dietary lipids to various hyperlipidaemias and atherosclerosis."}
{"id": "PMID:206271", "title": "Multipeaking of the compound electromyographic response to single nerve stimulus: its occurrence and prevention in an experimental model.", "content": "The compound electromyographic response to a single nerve stimulus was examined in the cat tibialis anterior muscle preparation, to determine the cause of and to find a method of preventing multipeaking of the waveform. Bundles of the sciatic nerve were separated and stimulated while the response was detected by unipolar electrodes and analysed with an instrument specifically designed for this purpose. It was found that the most cephalad bundle of the sciatic nerve at the sciatic notch innervated the tibialis anterior muscle and that restriction of stimulation to this bundle most readily rendered the response single-peaked. It is concluded that nerve-branching is a common cause, and therefore a straightforward alternative to \"repetitive response of the muscle\" as the explanation, of multipeaking of the neurally-elicited compound electromyogram. A method of eliciting and recording the compound electromyogram in the cat tibialis anterior model is described.", "contents": "Multipeaking of the compound electromyographic response to single nerve stimulus: its occurrence and prevention in an experimental model. The compound electromyographic response to a single nerve stimulus was examined in the cat tibialis anterior muscle preparation, to determine the cause of and to find a method of preventing multipeaking of the waveform. Bundles of the sciatic nerve were separated and stimulated while the response was detected by unipolar electrodes and analysed with an instrument specifically designed for this purpose. It was found that the most cephalad bundle of the sciatic nerve at the sciatic notch innervated the tibialis anterior muscle and that restriction of stimulation to this bundle most readily rendered the response single-peaked. It is concluded that nerve-branching is a common cause, and therefore a straightforward alternative to \"repetitive response of the muscle\" as the explanation, of multipeaking of the neurally-elicited compound electromyogram. A method of eliciting and recording the compound electromyogram in the cat tibialis anterior model is described."}
{"id": "PMID:206272", "title": "Biochemical and morphological comparison of two tumour-cell-aggregation factors from rat ascites hepatoma cells.", "content": "Two tumour-cell-aggregation factors, derived from rat ascites hepatoma cells, had different antigenicity; one was not absorbed by immunoadsorbent chromatography with anti-rat serum antibody and the other was. Their activities were both lost by digestion with trypsin, but remained unchanged by oxidation with periodate, suggesting the role of the protein portions in their molecules. The potency of the unabsorbed factor was inhibited specifically by alpha-methyl-D-mannoside or D-mannose, while that of the absorbed factor was inhibited specifically by N-acetyl-D-glucosamine, suggesting that these carbohydrates may be concerned with the respective receptor structures at the tumour-cell surface. The unabsorbed factor induced not only cell aggregation (as shown in the form of simple apposition) but also cell adhesiveness characterized by development of intermediate junctions, desmosomes and tight junctions, while the absorbed factor produced only simple apposition, suggesting their functional difference.", "contents": "Biochemical and morphological comparison of two tumour-cell-aggregation factors from rat ascites hepatoma cells. Two tumour-cell-aggregation factors, derived from rat ascites hepatoma cells, had different antigenicity; one was not absorbed by immunoadsorbent chromatography with anti-rat serum antibody and the other was. Their activities were both lost by digestion with trypsin, but remained unchanged by oxidation with periodate, suggesting the role of the protein portions in their molecules. The potency of the unabsorbed factor was inhibited specifically by alpha-methyl-D-mannoside or D-mannose, while that of the absorbed factor was inhibited specifically by N-acetyl-D-glucosamine, suggesting that these carbohydrates may be concerned with the respective receptor structures at the tumour-cell surface. The unabsorbed factor induced not only cell aggregation (as shown in the form of simple apposition) but also cell adhesiveness characterized by development of intermediate junctions, desmosomes and tight junctions, while the absorbed factor produced only simple apposition, suggesting their functional difference."}
{"id": "PMID:206273", "title": "Enhancing and inhibiting effects of spleen cells from tumour-bearing mice on growth of virus-induced primary sarcoma.", "content": "The effects of adoptive transfer of spleen cells from tumour-bearing mice on the growth of Moloney murine sarcoma virus (M-MuSV)-induced primary tumours in BALB/c mice were studied. The effects were in 2 directions, depending on the time of lymphocyte inoculation; when spleen cells from tumuor-bearing mice 12 days after M-MuSV inoculation were inoculated into recipient mice before M-MuSV inoculation, the appearance of tumours was significantly delayed and their incidence was reduced, whereas when these lymphocytes were inoculated after the development of tumours in recipient mice, tumour growth was significantly enhanced. The data indicated that these inhibiting and enhancing effects were mediated mainly by T cells. The mechanisms of the parodoxical effects were investigated.", "contents": "Enhancing and inhibiting effects of spleen cells from tumour-bearing mice on growth of virus-induced primary sarcoma. The effects of adoptive transfer of spleen cells from tumour-bearing mice on the growth of Moloney murine sarcoma virus (M-MuSV)-induced primary tumours in BALB/c mice were studied. The effects were in 2 directions, depending on the time of lymphocyte inoculation; when spleen cells from tumuor-bearing mice 12 days after M-MuSV inoculation were inoculated into recipient mice before M-MuSV inoculation, the appearance of tumours was significantly delayed and their incidence was reduced, whereas when these lymphocytes were inoculated after the development of tumours in recipient mice, tumour growth was significantly enhanced. The data indicated that these inhibiting and enhancing effects were mediated mainly by T cells. The mechanisms of the parodoxical effects were investigated."}
{"id": "PMID:206270", "title": "[Persistency of serum antibodies against Entamoeba histolytica].", "content": "With the purpose to determine the duration of serum antibodies against E. histolytica by means of the contraimmunoelectrophoresis technique, 31 patients with the diagnosis of intestinal or liver invasive amebiasis were included in this study. In 92.3% of the 13 patients subjected to transversal study, no specific antibodies were found from 10 to 24 months after the occurrence of amebic disease. In 64.7% of 17 children with liver amebiasis who were studied longitudinally, no serum antibodies were found between 4 to 10 months after the disease. The possible factors involved in the varaibility of the duration of serum antibodies against E. histolytica are discussed.", "contents": "[Persistency of serum antibodies against Entamoeba histolytica]. With the purpose to determine the duration of serum antibodies against E. histolytica by means of the contraimmunoelectrophoresis technique, 31 patients with the diagnosis of intestinal or liver invasive amebiasis were included in this study. In 92.3% of the 13 patients subjected to transversal study, no specific antibodies were found from 10 to 24 months after the occurrence of amebic disease. In 64.7% of 17 children with liver amebiasis who were studied longitudinally, no serum antibodies were found between 4 to 10 months after the disease. The possible factors involved in the varaibility of the duration of serum antibodies against E. histolytica are discussed."}
{"id": "PMID:206275", "title": "Neutrophil and eosinophil granulocytes in bacterial infection: sequential studies of cellular and serum levels of granule proteins.", "content": "The intraneutrophilic concentrations of lactoferrin, myeloperoxidase, collagenase and chymotrypsin-like cationic proteins were measured sequentially during acute bacterial infection. The serum levels of lactoferrin and myeloperoxidase were also followed as well as the 'eosinophil' cationic protein as a marker for eosinophil leucocytes. During the early course of infection there was a profound but reversible decrease of intraneutrophilic lactoferrin. The levels of cellular collagenase and chymotrypsin-like cationic proteins also tended to decrease reversibly during day 2-8 in most cases; myeloperoxidase levels were normal except for two cases. Serum myeloperoxidase and lactoferrin correlated with blood neutrophil counts. In spite of the absence of peripheral eosinophils the 'eosinophil' cationic proteins of serum were increased on the first day of infection, which may reflect increased eosinophil turnover.", "contents": "Neutrophil and eosinophil granulocytes in bacterial infection: sequential studies of cellular and serum levels of granule proteins. The intraneutrophilic concentrations of lactoferrin, myeloperoxidase, collagenase and chymotrypsin-like cationic proteins were measured sequentially during acute bacterial infection. The serum levels of lactoferrin and myeloperoxidase were also followed as well as the 'eosinophil' cationic protein as a marker for eosinophil leucocytes. During the early course of infection there was a profound but reversible decrease of intraneutrophilic lactoferrin. The levels of cellular collagenase and chymotrypsin-like cationic proteins also tended to decrease reversibly during day 2-8 in most cases; myeloperoxidase levels were normal except for two cases. Serum myeloperoxidase and lactoferrin correlated with blood neutrophil counts. In spite of the absence of peripheral eosinophils the 'eosinophil' cationic proteins of serum were increased on the first day of infection, which may reflect increased eosinophil turnover."}
{"id": "PMID:206276", "title": "Synthesis and characterization of 2-nitro-5-aziodobenzoylglycyloxytocin, an oxytocin photoaffinity label.", "content": "The oxytocin analogue, 2-nitro-5-azidobenzoylglycyloxytocin (NAB-Gly-oxytocin), has been synthesized and purified. The analogue is a full agonist for the stimulation of osmotic water flow in the toad urinary bladder (one-half maximal activity at 3.2 X 10(-6)M). It also enhances [14C]urea permeability in this tissue. Repetitive photolysis in the presence of NAB-Gly-oxytocin (8 X 10(-6)M) results in a progressive permanent inhibition of oxytocin stimulated urea permeability but does not alter hormone induced 3H2O movement. The inhibition is dependent on the photogeneration of the aryl nitrene intermediate and is relieved by protecting the hormone receptor with excess oxytocin (10(-6)M) during the photolysis. These results suggest that the photodependent permanent inhibition of the response to oxytocin in the toad bladder is due to covalent incorporation of the photoaffinity label, NAB-Gly-oxytocin, into the hormone receptor.", "contents": "Synthesis and characterization of 2-nitro-5-aziodobenzoylglycyloxytocin, an oxytocin photoaffinity label. The oxytocin analogue, 2-nitro-5-azidobenzoylglycyloxytocin (NAB-Gly-oxytocin), has been synthesized and purified. The analogue is a full agonist for the stimulation of osmotic water flow in the toad urinary bladder (one-half maximal activity at 3.2 X 10(-6)M). It also enhances [14C]urea permeability in this tissue. Repetitive photolysis in the presence of NAB-Gly-oxytocin (8 X 10(-6)M) results in a progressive permanent inhibition of oxytocin stimulated urea permeability but does not alter hormone induced 3H2O movement. The inhibition is dependent on the photogeneration of the aryl nitrene intermediate and is relieved by protecting the hormone receptor with excess oxytocin (10(-6)M) during the photolysis. These results suggest that the photodependent permanent inhibition of the response to oxytocin in the toad bladder is due to covalent incorporation of the photoaffinity label, NAB-Gly-oxytocin, into the hormone receptor."}
{"id": "PMID:206277", "title": "Small-angle X-ray scattering and differential scanning calorimetry studies on reversibly modified human-serum low density lipoproteins.", "content": "Small-angle x-ray scattering diagrams of human serum low density lipoprotein (LDL) were recorded at several temperatures in solutions of different freezing points. It was found that modifications of the x-ray patterns observed on cooling the lipoprotein samples below 0 degrees C are due to reversible alterations of the LDL surface structure induced by the freezing process (independent of temperature). With both intact and partially dehydrated LDL, differential scanning calorimetry (DSC) carried out in the body temperature range revealed a heat absorption characteristic of the transition from a liquid crystal to an isotropic liquid phase of cholesteryl esters within the lipoproteins (Deckelbaum, R. J., Shipley, R. J., Small, P. M., Lees, R. S., & George, P. K. (1975) Science 190, 392). However, small-angle x-ray scattering diagrams recorded with the same LDL sample before and after the partial removal of water were found to be very different: the scattering curve for intact LDL showed a strong band centered at (36 A)-1 which disappeared upon drying and reappeared upon restoring the water. Our results suggest that the presence of this signal strongly depends on the molecular structure of the lipoprotein surface.", "contents": "Small-angle X-ray scattering and differential scanning calorimetry studies on reversibly modified human-serum low density lipoproteins. Small-angle x-ray scattering diagrams of human serum low density lipoprotein (LDL) were recorded at several temperatures in solutions of different freezing points. It was found that modifications of the x-ray patterns observed on cooling the lipoprotein samples below 0 degrees C are due to reversible alterations of the LDL surface structure induced by the freezing process (independent of temperature). With both intact and partially dehydrated LDL, differential scanning calorimetry (DSC) carried out in the body temperature range revealed a heat absorption characteristic of the transition from a liquid crystal to an isotropic liquid phase of cholesteryl esters within the lipoproteins (Deckelbaum, R. J., Shipley, R. J., Small, P. M., Lees, R. S., & George, P. K. (1975) Science 190, 392). However, small-angle x-ray scattering diagrams recorded with the same LDL sample before and after the partial removal of water were found to be very different: the scattering curve for intact LDL showed a strong band centered at (36 A)-1 which disappeared upon drying and reappeared upon restoring the water. Our results suggest that the presence of this signal strongly depends on the molecular structure of the lipoprotein surface."}
{"id": "PMID:206279", "title": "Synthesis of mouse mammary tumor virus ribonucleic acid in isolated nuclei from cultured mammary tumor cells.", "content": "Glucocorticoid hormone treatment of GR cells, a cultured line derived from mouse mammary tumor tissue, selectively stimulates the rate of transcription of integrated proviral genes specifying mammary tumor virus (MTV). We have incubated isolated nuclei from these cells under conditions in which all three endogenous RNA polymerases appear to be active. RNA synthesized in vitro is distinguished from preexisting nuclear RNA by labeling the in vitro products with [3H]CTP, and the level of MTV RNA synthesis is measured by molecular hybridization with unlabeled viral DNA. Synthesis requires the addition of nucleoside triphosphates, and is inhibited by actinomycin D. Pretreatment of GR cells with dexamethasone, a synthetic glucocorticoid, has no significant effect on the amount of total RNA synthesis in isolated nuclei. In contrast, synthesis of MTR RNA is stimulated 10-20-fold in nuclei from dexamethasone-treated cells relative to untreated control nuclei; the sensitivity of in vitro viral RNA synthesis to inhibition by alpha-amanitin suggests that it is carried out exclusively by RNA polymerase II. The fraction of total RNA synthesis which is viral specific (about 0.2-0.4% in nuclei from dexamethasone-treated cells and 0.01-0.03% in controls) is similar to that detected in pulse labeled RNA from whole GR cells in culture. Our procedures for labeling and hybridization of RNA appear to avoid artifacts recently noted in other in vitro transcription systems.", "contents": "Synthesis of mouse mammary tumor virus ribonucleic acid in isolated nuclei from cultured mammary tumor cells. Glucocorticoid hormone treatment of GR cells, a cultured line derived from mouse mammary tumor tissue, selectively stimulates the rate of transcription of integrated proviral genes specifying mammary tumor virus (MTV). We have incubated isolated nuclei from these cells under conditions in which all three endogenous RNA polymerases appear to be active. RNA synthesized in vitro is distinguished from preexisting nuclear RNA by labeling the in vitro products with [3H]CTP, and the level of MTV RNA synthesis is measured by molecular hybridization with unlabeled viral DNA. Synthesis requires the addition of nucleoside triphosphates, and is inhibited by actinomycin D. Pretreatment of GR cells with dexamethasone, a synthetic glucocorticoid, has no significant effect on the amount of total RNA synthesis in isolated nuclei. In contrast, synthesis of MTR RNA is stimulated 10-20-fold in nuclei from dexamethasone-treated cells relative to untreated control nuclei; the sensitivity of in vitro viral RNA synthesis to inhibition by alpha-amanitin suggests that it is carried out exclusively by RNA polymerase II. The fraction of total RNA synthesis which is viral specific (about 0.2-0.4% in nuclei from dexamethasone-treated cells and 0.01-0.03% in controls) is similar to that detected in pulse labeled RNA from whole GR cells in culture. Our procedures for labeling and hybridization of RNA appear to avoid artifacts recently noted in other in vitro transcription systems."}
{"id": "PMID:206281", "title": "Kinetic studies on the reactions catalyzed by chorismate mutase-prephenate dehydrogenase from Aerobacter aerogenes.", "content": "Steady-state kinetic techniques have been used to investigate each of the reactions catalyzed by the bifunctional enzyme, chorismate mutase-prephenate dehydrogenase, from Aerobacter aerogenes. The results of steady-state velocity studies in the absence of products, as well as product and dead-end inhibition studies, suggest that the prephenate dehydrogenase reaction conforms to a rapid equilibrium random mechanism which involes the formation of two dead-end complexes, viz, enzyme-NADH-prephenate and enzyme-NAD+-hydroxyphenylpyruvate. Chorismate functions as an activator of the dehydrogenase while both prephenate and hydroxyphenylpyruvate acted as competitive inhibitors in the mutase reaction. By contrast. bpth NAD+ and NADH function as activators of the mutase. Values of the kinetic parameters associated with the mutase and dehydrogenase reactions have been determined and the results discussed in terms of possible relationships between the catalytic sites for the two reactions. The data appear to be consistent with the enzyme having either a single site at which both reactions occur or two separate sites which possess similar kinetic properties.", "contents": "Kinetic studies on the reactions catalyzed by chorismate mutase-prephenate dehydrogenase from Aerobacter aerogenes. Steady-state kinetic techniques have been used to investigate each of the reactions catalyzed by the bifunctional enzyme, chorismate mutase-prephenate dehydrogenase, from Aerobacter aerogenes. The results of steady-state velocity studies in the absence of products, as well as product and dead-end inhibition studies, suggest that the prephenate dehydrogenase reaction conforms to a rapid equilibrium random mechanism which involes the formation of two dead-end complexes, viz, enzyme-NADH-prephenate and enzyme-NAD+-hydroxyphenylpyruvate. Chorismate functions as an activator of the dehydrogenase while both prephenate and hydroxyphenylpyruvate acted as competitive inhibitors in the mutase reaction. By contrast. bpth NAD+ and NADH function as activators of the mutase. Values of the kinetic parameters associated with the mutase and dehydrogenase reactions have been determined and the results discussed in terms of possible relationships between the catalytic sites for the two reactions. The data appear to be consistent with the enzyme having either a single site at which both reactions occur or two separate sites which possess similar kinetic properties."}
{"id": "PMID:206282", "title": "Sodium transport by isolated bullfrog small intestine. Effect of prostaglandin E1.", "content": "Addition of 446 micron prostaglandin E1 (PGE1) to the serosal medium of isolated short-circuited bullfrog small intestine elicited small increases transmural potential difference and short-circuit current while addition of PGE1 to the mucosal medium caused no change in the electrical parameters. Addition of 100 micron indomethacin to the mucosal medium inhibited both potential difference and short-circuit current with a resultant increase in steady-state tissue resistance. In the presence of mucosal 100 micron indomethacin, serosal 60 micron PGE1 markedly stimulated transmural potential difference and short-circuit current with a resultant decrease in steady-state tissue resistance. Serosal arachidonic acid (330 micron) stimulated transmural potential difference and short-circuit current and this effect was abolished by the addition of 100 micron indomethacin to the mucosal medium. Serosal 60 micron PGE1 only stimulated the M (mucosa) leads to S (serosa) unidirectional flux of sodium. These results strongly suggest that the PGE1 action is mediated either via a series of metabolic reactions which possibly increase the permeability of the mucosal membrane to sodium or via direct stimulation of rheogenic sodium pump activity.", "contents": "Sodium transport by isolated bullfrog small intestine. Effect of prostaglandin E1. Addition of 446 micron prostaglandin E1 (PGE1) to the serosal medium of isolated short-circuited bullfrog small intestine elicited small increases transmural potential difference and short-circuit current while addition of PGE1 to the mucosal medium caused no change in the electrical parameters. Addition of 100 micron indomethacin to the mucosal medium inhibited both potential difference and short-circuit current with a resultant increase in steady-state tissue resistance. In the presence of mucosal 100 micron indomethacin, serosal 60 micron PGE1 markedly stimulated transmural potential difference and short-circuit current with a resultant decrease in steady-state tissue resistance. Serosal arachidonic acid (330 micron) stimulated transmural potential difference and short-circuit current and this effect was abolished by the addition of 100 micron indomethacin to the mucosal medium. Serosal 60 micron PGE1 only stimulated the M (mucosa) leads to S (serosa) unidirectional flux of sodium. These results strongly suggest that the PGE1 action is mediated either via a series of metabolic reactions which possibly increase the permeability of the mucosal membrane to sodium or via direct stimulation of rheogenic sodium pump activity."}
{"id": "PMID:206283", "title": "Correlation between the thermotropic behavior of sphingomyelin liposomes and sphingomyelin hydrolysis by sphingomyelinase of Staphylococcus aureus.", "content": "The hydrolysis of D-erythro beef brain sphingomyelin and D,L-erythro-N-palmitoylsphingomyelin dispersed as multilamellar liposomes by sphingomyelinase of Staphylococcus aureus is correlated with the thermotropic behavior of the sphingomyelins. In both cases maximal enzymatic hydrolysis was achieved at the beginning of the gel to liquid crystalline phase transition (30 degrees C for beef brain sphingomyelin and 41 degrees C for N-palmitoylsphingosine-phosphorylcholine) with much lower activity both below and above these temperatures. The enzymatic activity was depressed in the presence of cholesterol in the bilayer which also depressed the phase-transition. The profile of the enzymatic activity is explained by the uniqueness of the lipid molecules arrangement at the phase transition.", "contents": "Correlation between the thermotropic behavior of sphingomyelin liposomes and sphingomyelin hydrolysis by sphingomyelinase of Staphylococcus aureus. The hydrolysis of D-erythro beef brain sphingomyelin and D,L-erythro-N-palmitoylsphingomyelin dispersed as multilamellar liposomes by sphingomyelinase of Staphylococcus aureus is correlated with the thermotropic behavior of the sphingomyelins. In both cases maximal enzymatic hydrolysis was achieved at the beginning of the gel to liquid crystalline phase transition (30 degrees C for beef brain sphingomyelin and 41 degrees C for N-palmitoylsphingosine-phosphorylcholine) with much lower activity both below and above these temperatures. The enzymatic activity was depressed in the presence of cholesterol in the bilayer which also depressed the phase-transition. The profile of the enzymatic activity is explained by the uniqueness of the lipid molecules arrangement at the phase transition."}
{"id": "PMID:206284", "title": "Magnetic resonance studies of eukaryotic cells. III. Spin labeled fatty acids in the plasma membrane.", "content": "XC Sarcoma, Vero and Aedes aegypti plasma membranes have been studied in viable cells and in purified membrane of XC Sarcoma cells by the spin label method. The temperature dependence of the order parameter of fatty acid spin labels is found to be linear in all three cells and membrane and shows no evidence of a lipid phase transition. The order parameter of the fatty acid labels substituted at the 5-position is shown to increase as a function of the cholesterol: phospholipid molar ratio in cells that have been studied to date. Cells attached to their growing surface are studied for the first time by electron paramagnetic resonance spectroscopy (EPR). The resulting spectra are anisotropic due to the non-spherical shape of the cells and show that these labels orient preferentially perpendicular to the cell surface. The viscosity of the extracted XC cell membrane is estimated to be 2.5 P from rotational correlation time measurements of the spin label 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO).", "contents": "Magnetic resonance studies of eukaryotic cells. III. Spin labeled fatty acids in the plasma membrane. XC Sarcoma, Vero and Aedes aegypti plasma membranes have been studied in viable cells and in purified membrane of XC Sarcoma cells by the spin label method. The temperature dependence of the order parameter of fatty acid spin labels is found to be linear in all three cells and membrane and shows no evidence of a lipid phase transition. The order parameter of the fatty acid labels substituted at the 5-position is shown to increase as a function of the cholesterol: phospholipid molar ratio in cells that have been studied to date. Cells attached to their growing surface are studied for the first time by electron paramagnetic resonance spectroscopy (EPR). The resulting spectra are anisotropic due to the non-spherical shape of the cells and show that these labels orient preferentially perpendicular to the cell surface. The viscosity of the extracted XC cell membrane is estimated to be 2.5 P from rotational correlation time measurements of the spin label 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO)."}
{"id": "PMID:206285", "title": "Purification and characterization of a long chain, fatty-acid-binding protein supplying the mitochondrial beta-oxidative system in the heart.", "content": "A fatty-acid-binding protein with a molecular weight of approximately 12 000 was purified from rat heart and the binding investigated by electron spin resonance. The stearic acid bound to the protein was found to be transferred to the mitochondrial beta-oxidative system, suggesting a role as transcytoplasmic fatty acid carrier for this protein. For the first time a physiological cytoplasmic protein was used as a carrier supplying the mitochondrial beta-oxidative system. A new mechanism of action is proposed to explain the control exerted by this type of protein in some membrane-linked enzymatic processes.", "contents": "Purification and characterization of a long chain, fatty-acid-binding protein supplying the mitochondrial beta-oxidative system in the heart. A fatty-acid-binding protein with a molecular weight of approximately 12 000 was purified from rat heart and the binding investigated by electron spin resonance. The stearic acid bound to the protein was found to be transferred to the mitochondrial beta-oxidative system, suggesting a role as transcytoplasmic fatty acid carrier for this protein. For the first time a physiological cytoplasmic protein was used as a carrier supplying the mitochondrial beta-oxidative system. A new mechanism of action is proposed to explain the control exerted by this type of protein in some membrane-linked enzymatic processes."}
{"id": "PMID:206286", "title": "[Paramagnetic centers and photochemical reactions of photosystem 2 subchloroplast fragments].", "content": "ESR signals of highly purified subchloroplast fragments containing the Photosystem 2 (PS 2) were obtained. Reversibility of the ESR II signal in darkness in the presence of dichlorophenolindophenol (DCPIP) was observed. Reduction of DCPIP with chloroplast fragments in the absence of exogenous donors takes place in light without simultaneous liberation of O2. Electron transfer may be blocked by the displacement of manganese with Mg2+ and Ba2+ bivalent cations. Cd2+ cations partially suppress the electron transfer catalysed by PS 2. The inhibiting effect of Cd2+ is removed in the presence of exogenous Mn2+ or hydroxylamine.", "contents": "[Paramagnetic centers and photochemical reactions of photosystem 2 subchloroplast fragments]. ESR signals of highly purified subchloroplast fragments containing the Photosystem 2 (PS 2) were obtained. Reversibility of the ESR II signal in darkness in the presence of dichlorophenolindophenol (DCPIP) was observed. Reduction of DCPIP with chloroplast fragments in the absence of exogenous donors takes place in light without simultaneous liberation of O2. Electron transfer may be blocked by the displacement of manganese with Mg2+ and Ba2+ bivalent cations. Cd2+ cations partially suppress the electron transfer catalysed by PS 2. The inhibiting effect of Cd2+ is removed in the presence of exogenous Mn2+ or hydroxylamine."}
{"id": "PMID:206287", "title": "[Light-dependent reactions of Mn2+ and P700+ in chloroplasts during flash illumination].", "content": "The changes of the light-induced ESR signal I and exogeneous Mn2+ ions in chloroplasts of Vicia faba plants have been studied under short flash excitation and weak background far red illumination. It is shown that Mn2+ ions reactivate the noncyclic electron transport in chloroplast previously inactivated with high tris concentrations under pulse illumination. Simultaneously with P700+ reduction the ESR signal of free Mn2+ ions decays stoichometrically to P700+ reduction.", "contents": "[Light-dependent reactions of Mn2+ and P700+ in chloroplasts during flash illumination]. The changes of the light-induced ESR signal I and exogeneous Mn2+ ions in chloroplasts of Vicia faba plants have been studied under short flash excitation and weak background far red illumination. It is shown that Mn2+ ions reactivate the noncyclic electron transport in chloroplast previously inactivated with high tris concentrations under pulse illumination. Simultaneously with P700+ reduction the ESR signal of free Mn2+ ions decays stoichometrically to P700+ reduction."}
{"id": "PMID:206291", "title": "Reactivity of antiinflammatory and superoxide dismutase active Cu(II)-salicylates.", "content": "The activity of chelated Cu(II) with four different aspirin-like drugs in various superoxide dismutase assays was examined. Prior to these studies the oxidation state of the involved copper was measured by x-ray photoelectron spectrometry and was found to be +II throughout. All copper complexes were able to suppress the xanthine-xanthine oxidase mediated reduction of both cytochrome c and nitroblue tetrazolium as well as the formazan formation by KO2 in a specific manner. The hydroxylation of benzo-[alpha]-pyrene as well as the demethylation of 7-ethoxycoumarin using induced hepatic rat microsomes could be successfully inhibited by the employed Cu(II) chelates. Cu(II)-acetylsalicylate was the most active copper complex. Our findings support the proposal that Cu(II) chelates are the active forms of aspirin-like antiinflammatory agents.", "contents": "Reactivity of antiinflammatory and superoxide dismutase active Cu(II)-salicylates. The activity of chelated Cu(II) with four different aspirin-like drugs in various superoxide dismutase assays was examined. Prior to these studies the oxidation state of the involved copper was measured by x-ray photoelectron spectrometry and was found to be +II throughout. All copper complexes were able to suppress the xanthine-xanthine oxidase mediated reduction of both cytochrome c and nitroblue tetrazolium as well as the formazan formation by KO2 in a specific manner. The hydroxylation of benzo-[alpha]-pyrene as well as the demethylation of 7-ethoxycoumarin using induced hepatic rat microsomes could be successfully inhibited by the employed Cu(II) chelates. Cu(II)-acetylsalicylate was the most active copper complex. Our findings support the proposal that Cu(II) chelates are the active forms of aspirin-like antiinflammatory agents."}
{"id": "PMID:206292", "title": "Coordination chemistry of molybdenum and tungsten--VIII. Oxomolybdenum(V) complexes of 8-hydroxyquinoline and relevance of EPR spectra to binding sites in flavoenzymes.", "content": "MoOCl3(THF)2 (THF = tetrahydrofuran) reacts with 8-hydroxyquinoline (QH) to form [MoOCl3(QH)2], which contains neutral monodentate ligands, [MoOCl(Q)2], and anionic bidentate ligands, and the dimeric [Mo2O3(Q)4], which contains anionic bidentate ligands and both terminal and bridging oxo donors. In dichloromethane [MoOCl3(QH)2] dissolves to give three species, and epr measurements identify these as unchanged [MoOCl3(QH)2], [MoOCl(Q)2] and a third species characterised by a value of 1.979. No g value of this magnitude has previously been obtained for molybdenum(V) complexes which do not contain sulphur donors, and the significance of epr measurements as an indication of the nature of molybdenum coordination in flavoenzymes must be questioned. These complexes have also been characterised by vibrational and electronic spectral measurements.", "contents": "Coordination chemistry of molybdenum and tungsten--VIII. Oxomolybdenum(V) complexes of 8-hydroxyquinoline and relevance of EPR spectra to binding sites in flavoenzymes. MoOCl3(THF)2 (THF = tetrahydrofuran) reacts with 8-hydroxyquinoline (QH) to form [MoOCl3(QH)2], which contains neutral monodentate ligands, [MoOCl(Q)2], and anionic bidentate ligands, and the dimeric [Mo2O3(Q)4], which contains anionic bidentate ligands and both terminal and bridging oxo donors. In dichloromethane [MoOCl3(QH)2] dissolves to give three species, and epr measurements identify these as unchanged [MoOCl3(QH)2], [MoOCl(Q)2] and a third species characterised by a value of 1.979. No g value of this magnitude has previously been obtained for molybdenum(V) complexes which do not contain sulphur donors, and the significance of epr measurements as an indication of the nature of molybdenum coordination in flavoenzymes must be questioned. These complexes have also been characterised by vibrational and electronic spectral measurements."}
{"id": "PMID:206288", "title": "[Cytochrome concentration in the liver at different stages of adaptation to cold].", "content": "Concentration of cytochroms in the liver of adult male rats has been studied during the acclimation to cold. One group of rats was kept at about 24 degrees, another at 2--4 degrees. After a month of acclimation to cold the cytochroms concentration in the liver increased, whereas the mitochondrial concentration of cytochroms remained unchanged. It is possible to distinguish three steps of cytochroms concentration changes; 1. on the 9th day of acclimation to cold cytochroms concentration increased 1.5--2 times; 2. by the 14th day the cytochroms concentration decreased (to the control level and lower); 3. after about one month of acclimation to cold the cytochroms concentration increased again. In the skeletal muscle it increased on the 14th (but not on the 9th) day.", "contents": "[Cytochrome concentration in the liver at different stages of adaptation to cold]. Concentration of cytochroms in the liver of adult male rats has been studied during the acclimation to cold. One group of rats was kept at about 24 degrees, another at 2--4 degrees. After a month of acclimation to cold the cytochroms concentration in the liver increased, whereas the mitochondrial concentration of cytochroms remained unchanged. It is possible to distinguish three steps of cytochroms concentration changes; 1. on the 9th day of acclimation to cold cytochroms concentration increased 1.5--2 times; 2. by the 14th day the cytochroms concentration decreased (to the control level and lower); 3. after about one month of acclimation to cold the cytochroms concentration increased again. In the skeletal muscle it increased on the 14th (but not on the 9th) day."}
{"id": "PMID:206294", "title": "[Inhibitors of exonuclease A5].", "content": "Over 30 compounds resembling to or being structural elements of the minimal substrate of exonuclease A5 were tested for their ability to inhibit the reaction catalyzed by this nuclease. The compounds containing less than two phosphate groups were shown to possess a low inhibitory activity, if any. CDP, double-stranded DNA and nucleoside-3',5'-diphosphates (pNp) proved to be effective exonuclease A5 inhibitors. Pyrophosphate stimulated the reaction in the case of low molecular weight substrates only. For the inhibitory activity of pNp to occur, the intactness of the nucleoside moiety as a whole was shown to be necessary, the activity level depending on the structure of both the base and the sugar components. A competitive mechanism of the inhibitory action was demonstrated for pTp, pdCp, pdGp, pdAp and pUp and the Ki values were determined. The affinity for the inhibitor decreased in the following order: pdCp greater than or equal to pTp greater than pdGp greater than pdAp. Ki for pdCp and pTp were found to be approximately 3.10(-6) M. The investigation of the inhibition mechanism as well the determination of Ki were accomplished with the help of homogenous low molecular weight substrates--ApApA and the phosphoamide MeOPheNH(pdA)2. These were chosen after kinetic parameters determination of the hydrolysis of 22 exonuclease A5 substrates, predominatly of the RpNpN type. On the basis of data obtained the specificity of exonuclease A5 is also discussed. Possible usefulness of immobilized competitive inhibitors of the pNp type not only for single nuclease isolation but for the separation of a mixture of different nucleases is considered. This possibility is based on the almost universal inhibitory effect of pNp on different nucleases and at the same time on their different affinity for the enzymes. In particular, this approach might be useful for the elimination of exonucleases and some other nucleolytic enzymes from the preparations of endonucleases-restrictases.", "contents": "[Inhibitors of exonuclease A5]. Over 30 compounds resembling to or being structural elements of the minimal substrate of exonuclease A5 were tested for their ability to inhibit the reaction catalyzed by this nuclease. The compounds containing less than two phosphate groups were shown to possess a low inhibitory activity, if any. CDP, double-stranded DNA and nucleoside-3',5'-diphosphates (pNp) proved to be effective exonuclease A5 inhibitors. Pyrophosphate stimulated the reaction in the case of low molecular weight substrates only. For the inhibitory activity of pNp to occur, the intactness of the nucleoside moiety as a whole was shown to be necessary, the activity level depending on the structure of both the base and the sugar components. A competitive mechanism of the inhibitory action was demonstrated for pTp, pdCp, pdGp, pdAp and pUp and the Ki values were determined. The affinity for the inhibitor decreased in the following order: pdCp greater than or equal to pTp greater than pdGp greater than pdAp. Ki for pdCp and pTp were found to be approximately 3.10(-6) M. The investigation of the inhibition mechanism as well the determination of Ki were accomplished with the help of homogenous low molecular weight substrates--ApApA and the phosphoamide MeOPheNH(pdA)2. These were chosen after kinetic parameters determination of the hydrolysis of 22 exonuclease A5 substrates, predominatly of the RpNpN type. On the basis of data obtained the specificity of exonuclease A5 is also discussed. Possible usefulness of immobilized competitive inhibitors of the pNp type not only for single nuclease isolation but for the separation of a mixture of different nucleases is considered. This possibility is based on the almost universal inhibitory effect of pNp on different nucleases and at the same time on their different affinity for the enzymes. In particular, this approach might be useful for the elimination of exonucleases and some other nucleolytic enzymes from the preparations of endonucleases-restrictases."}
{"id": "PMID:206295", "title": "Stochastic ESR analysis of rat liver and hepatoma mitochondrial lipids.", "content": "A commonly used model for the interaction of the motional narrowing of ESR lines is shown to be qualitatively misleading. An analysis of lipid extracts of mitochondrial preparations labeled with 12-nitroxide stearic acid produced linear plots of the logarithm of the correlation time versus the reciprocal of the absolute temperature when analyzed with stochastic computer simulations. However, when the data were analyzed with isotropic Lorentzian line shape approximations, nonlinear plots were obtained.", "contents": "Stochastic ESR analysis of rat liver and hepatoma mitochondrial lipids. A commonly used model for the interaction of the motional narrowing of ESR lines is shown to be qualitatively misleading. An analysis of lipid extracts of mitochondrial preparations labeled with 12-nitroxide stearic acid produced linear plots of the logarithm of the correlation time versus the reciprocal of the absolute temperature when analyzed with stochastic computer simulations. However, when the data were analyzed with isotropic Lorentzian line shape approximations, nonlinear plots were obtained."}
{"id": "PMID:206289", "title": "[Comparative study of the photopotential and EPR signal arising after photooxidation of metal substituted pheophytins].", "content": "Ethanolic solutions of Zn-, Cd-Phe a and b and Chl a and b with p-benzoquinone as electron acceptor have been studied at pH 4. In all systems positive photopotentials and singlet ESR lines of the pigment cation radicals are observed. A conclusion is made that the photopotential is only partly attributable to an electrode reaction of the cation radicals, to a greater extent arising due to unknown, non-radical particles.", "contents": "[Comparative study of the photopotential and EPR signal arising after photooxidation of metal substituted pheophytins]. Ethanolic solutions of Zn-, Cd-Phe a and b and Chl a and b with p-benzoquinone as electron acceptor have been studied at pH 4. In all systems positive photopotentials and singlet ESR lines of the pigment cation radicals are observed. A conclusion is made that the photopotential is only partly attributable to an electrode reaction of the cation radicals, to a greater extent arising due to unknown, non-radical particles."}
{"id": "PMID:206290", "title": "[Study of the responses of tumor and normal tissues to exposure to ionizing radiation by the EPR method. I. Comparison of the low temperature EPR spectra of irradiated tumor and normal tissues].", "content": "ESR spectra of liver samples of normal mice and liver tumour samples of mice (line C3HA) injected hepatomo 22-a irradiated in the dose of 1 Mrad at --196 degrees C were studied. The ESR spectra of normal and tumour tissues irradiated at --196 degrees C are shown to differ. Only the ESR spectra of tumour and liver of the tumour host is characterized by an asymmetric signal with deltaH=6 Oe and g=2.0005 (\"tumour\" signal). The intensity of the \"tumour\" signal depends on the developmental stage of hepatoma. It is changed after the animals are injected with ionol.", "contents": "[Study of the responses of tumor and normal tissues to exposure to ionizing radiation by the EPR method. I. Comparison of the low temperature EPR spectra of irradiated tumor and normal tissues]. ESR spectra of liver samples of normal mice and liver tumour samples of mice (line C3HA) injected hepatomo 22-a irradiated in the dose of 1 Mrad at --196 degrees C were studied. The ESR spectra of normal and tumour tissues irradiated at --196 degrees C are shown to differ. Only the ESR spectra of tumour and liver of the tumour host is characterized by an asymmetric signal with deltaH=6 Oe and g=2.0005 (\"tumour\" signal). The intensity of the \"tumour\" signal depends on the developmental stage of hepatoma. It is changed after the animals are injected with ionol."}
{"id": "PMID:206298", "title": "Role of microtubules in granulocyte adherence.", "content": "The adherence of human polymorphonuclear leukocytes (PMN) to nylon fibers is inhibited in a dose-dependent fashion by exposure in vitro of these cells to either colchicine or VM-26, both of which agents prevent microtubule assembly. Mean adherence of human PMN was 48% +/- 2%, following treatment with 10(-5) M colchicine or 10(-4) M VM-26 it was reduced to 31% +/- 2% and 7%, respectively. Peritoneal PMN obtained from mice and mink with Chediak-Higashi syndrome (CHS) thought to have a microtubule-membrane disorder affecting the PMN had a mean adherence of 29% +/- 3% and 40% +/- 8% compared to control values of 46% +/- 5% and 73% +/- 8%, respectively, from the mice and mink. Both ascorbic acid and bethanechol, shown previously to enhance microtubule assembly in humans with CHS, normalized granulocyte adherence in PMN obtained from mice with CHS. Cyclic nucleotide levels were not altered by treatment of human PMN with colchicine, nor did they differ between normal and CHS animals. Thus it appears that the state of microtubule assembly may directly affect the properties of the PMN plasma membrane without requiring alterations of cyclic nucleotides as an intermediary.", "contents": "Role of microtubules in granulocyte adherence. The adherence of human polymorphonuclear leukocytes (PMN) to nylon fibers is inhibited in a dose-dependent fashion by exposure in vitro of these cells to either colchicine or VM-26, both of which agents prevent microtubule assembly. Mean adherence of human PMN was 48% +/- 2%, following treatment with 10(-5) M colchicine or 10(-4) M VM-26 it was reduced to 31% +/- 2% and 7%, respectively. Peritoneal PMN obtained from mice and mink with Chediak-Higashi syndrome (CHS) thought to have a microtubule-membrane disorder affecting the PMN had a mean adherence of 29% +/- 3% and 40% +/- 8% compared to control values of 46% +/- 5% and 73% +/- 8%, respectively, from the mice and mink. Both ascorbic acid and bethanechol, shown previously to enhance microtubule assembly in humans with CHS, normalized granulocyte adherence in PMN obtained from mice with CHS. Cyclic nucleotide levels were not altered by treatment of human PMN with colchicine, nor did they differ between normal and CHS animals. Thus it appears that the state of microtubule assembly may directly affect the properties of the PMN plasma membrane without requiring alterations of cyclic nucleotides as an intermediary."}
{"id": "PMID:206302", "title": "Involvement of the periaqueductal grey matter and spinal 5-hydroxytryptaminergic pathways in morphine analgesia: effcts of lesions and 5-hydroxytryptamine depletion.", "content": "1 Electrolytic lesions of the periaqueductal grey matter (PAG) were made in rats. The analgesia produced by intraperitoneal injection of morphine (10 and 20 mg/kg), tested by the tail flick and hot plate methods, was substantially reduced in the lesioned rats. Baseline pain thresholds were unaffected by the lesions.2 The lesion effects were not due to damage to the dorsal raph\u00e9 nucleus. The extent of histologically determined damage to the dorsal raph\u00e9 and the resulting decrease in striatal 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations did not correlate with the reduction in morphine analgesia produced by the lesion. Furthermore, microinjections of 5, 6-dihydroxytryptamine (5,6-DHT) into the dorsal raph\u00e9 nucleus produced a similar fall in 5-HIAA levels but had no effect on morphine analgesia.3 Selective destruction of the periventricular catecholamine system produced by microinjection of 6-hydroxydopamine (6-OHDA) caused a slight decrease in morphine analgesia, thus raising the possibility that catecholamines may be involved in the action of morphine in the PAG.4 5,7-Dihydroxytryptamine-induced lesions of the spinal cord 5-hydroxytryptaminergic pathways reduced cord 5-HT concentration by 70% and markedly attenuated morphine analgesia as determined by the tail flick test.5 These experiments provide additional evidence that the PAG is a major site of action of opiates in producing analgesia. Furthermore, they have demonstrated the probable involvement of spinal 5-hydroxytryptaminergic pathways in the mediation of opiate analgesic effects.", "contents": "Involvement of the periaqueductal grey matter and spinal 5-hydroxytryptaminergic pathways in morphine analgesia: effcts of lesions and 5-hydroxytryptamine depletion. 1 Electrolytic lesions of the periaqueductal grey matter (PAG) were made in rats. The analgesia produced by intraperitoneal injection of morphine (10 and 20 mg/kg), tested by the tail flick and hot plate methods, was substantially reduced in the lesioned rats. Baseline pain thresholds were unaffected by the lesions.2 The lesion effects were not due to damage to the dorsal raph\u00e9 nucleus. The extent of histologically determined damage to the dorsal raph\u00e9 and the resulting decrease in striatal 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations did not correlate with the reduction in morphine analgesia produced by the lesion. Furthermore, microinjections of 5, 6-dihydroxytryptamine (5,6-DHT) into the dorsal raph\u00e9 nucleus produced a similar fall in 5-HIAA levels but had no effect on morphine analgesia.3 Selective destruction of the periventricular catecholamine system produced by microinjection of 6-hydroxydopamine (6-OHDA) caused a slight decrease in morphine analgesia, thus raising the possibility that catecholamines may be involved in the action of morphine in the PAG.4 5,7-Dihydroxytryptamine-induced lesions of the spinal cord 5-hydroxytryptaminergic pathways reduced cord 5-HT concentration by 70% and markedly attenuated morphine analgesia as determined by the tail flick test.5 These experiments provide additional evidence that the PAG is a major site of action of opiates in producing analgesia. Furthermore, they have demonstrated the probable involvement of spinal 5-hydroxytryptaminergic pathways in the mediation of opiate analgesic effects."}
{"id": "PMID:206303", "title": "Effects of prostaglandin E2 and a prostaglandin endoperoxide analogue on neuroeffector transmission in the rat anococcygeus msucle.", "content": "1 Investigations were made into the effects of prostaglandin E(2) (PGE(2)) and a prostaglandin endoperoxide analogue (Upjohn compound U-46619) on the responses of the rat anococcygeus muscle to field stimulation of the intrinsic sympathetic nerves, and to exogenous noradrenaline. The effects of PGE(2) on responses to stimulation of intrinsic inhibitory nerves were also studied.2 PGE(2) (5.6 x 10(-8) or 2.8 x 10(-6) mol/l) decreased motor (sympathetic) responses to field stimulation at all frequencies tested (2 to 24 Hz). The prostaglandin also reduced the inhibitory responses to field stimulation, seen when the tone of the preparation had been raised and its sympathetic innervation had been blocked by guanethidine. However, these inhibitory responses were also reduced by other spasmogens (carbachol and 5-hydroxytryptamine) which, like PGE(2), further increased the tone of guanethidine-treated preparations.3 At a concentration of 5.6 x 10(-8) mol/l, PGE(2) had no effect on responses to noradrenaline, whereas at a fifty-fold higher concentration the prostaglandin potentiated these.4 Unlike PGE(2), U-46619 (5.6 x 10(-8) mol/l) greatly potentiated motor responses to field stimulation, at frequencies from 0.75 to 24 Hz. This effect did not represent a specific facilitation of sympathetic neurotransmission, as responses to carbachol and 5-hydroxytryptamine, as well as to noradrenaline, were also potentiated.5 The results are discussed in relation to the effects of prostaglandins and prostaglandin endoperoxides on neuroeffector transmission in other sympathetically innervated tissues. It is concluded that PGE(2) inhibits sympathetic neurotransmission in the rat anococcygenus muscle by a prejunctional action, whereas the predominant effect of U-46619 is direct excitation of the muscle. The effect of PGE(2) on inhibitory responses to field stimulation may represent an interference with inhibitory neuroeffector transmission in this tissue, or may simply be a consequence of the spasmogenic action of the prostaglandin.", "contents": "Effects of prostaglandin E2 and a prostaglandin endoperoxide analogue on neuroeffector transmission in the rat anococcygeus msucle. 1 Investigations were made into the effects of prostaglandin E(2) (PGE(2)) and a prostaglandin endoperoxide analogue (Upjohn compound U-46619) on the responses of the rat anococcygeus muscle to field stimulation of the intrinsic sympathetic nerves, and to exogenous noradrenaline. The effects of PGE(2) on responses to stimulation of intrinsic inhibitory nerves were also studied.2 PGE(2) (5.6 x 10(-8) or 2.8 x 10(-6) mol/l) decreased motor (sympathetic) responses to field stimulation at all frequencies tested (2 to 24 Hz). The prostaglandin also reduced the inhibitory responses to field stimulation, seen when the tone of the preparation had been raised and its sympathetic innervation had been blocked by guanethidine. However, these inhibitory responses were also reduced by other spasmogens (carbachol and 5-hydroxytryptamine) which, like PGE(2), further increased the tone of guanethidine-treated preparations.3 At a concentration of 5.6 x 10(-8) mol/l, PGE(2) had no effect on responses to noradrenaline, whereas at a fifty-fold higher concentration the prostaglandin potentiated these.4 Unlike PGE(2), U-46619 (5.6 x 10(-8) mol/l) greatly potentiated motor responses to field stimulation, at frequencies from 0.75 to 24 Hz. This effect did not represent a specific facilitation of sympathetic neurotransmission, as responses to carbachol and 5-hydroxytryptamine, as well as to noradrenaline, were also potentiated.5 The results are discussed in relation to the effects of prostaglandins and prostaglandin endoperoxides on neuroeffector transmission in other sympathetically innervated tissues. It is concluded that PGE(2) inhibits sympathetic neurotransmission in the rat anococcygenus muscle by a prejunctional action, whereas the predominant effect of U-46619 is direct excitation of the muscle. The effect of PGE(2) on inhibitory responses to field stimulation may represent an interference with inhibitory neuroeffector transmission in this tissue, or may simply be a consequence of the spasmogenic action of the prostaglandin."}
{"id": "PMID:206304", "title": "Action of guanethidine on rabbit atrial membranes.", "content": "1 Intracellular potentials were recorded in driven left atria from reserpine-treated rabbits. Guanethidine 2 X 10(-5) M slightly increased Vmax and shortened the total duration (TD) of the action potential (AP) without causing hyperpolarization. For the first 30 min after 4 X 10(-4) M, Vmax increased without hyperpolarization and AP height increased slightly. Thereafter, Vmax and height decreased with a slight and gradual depolarization. This depolarization was irreversible. TD was increased after 15 minutes. Guanethidine 2 X 10(-3) M initially decreased Vmax and height before causing depolarization. 2. Pretreatment with tetrodotoxin (TTX) 1.6 X 10(-7) M prevented or reversed the initial increases in Vmax, height and TD induced by guanethidine (4 X 10(-4) M). 3 TTX 3.1 to 6.2 X 10(-6) M, added 15 or 30 min after guanethidine 4 X 10(-4) M, delayed or prevented depolarization by guanethidine. 4 Ouabain 10(-5) M incubated for 20 and 90 min greatly inhibited Na+, K+-adenosine triphosphatase and K+-phosphatase activities; guanethidine was without effect. 5 Guanethidine probably increases resting sodium permeability after the promotion of increases in sodium permeability during the AP. High doses of the drug decrease sodium permeability during the AP.", "contents": "Action of guanethidine on rabbit atrial membranes. 1 Intracellular potentials were recorded in driven left atria from reserpine-treated rabbits. Guanethidine 2 X 10(-5) M slightly increased Vmax and shortened the total duration (TD) of the action potential (AP) without causing hyperpolarization. For the first 30 min after 4 X 10(-4) M, Vmax increased without hyperpolarization and AP height increased slightly. Thereafter, Vmax and height decreased with a slight and gradual depolarization. This depolarization was irreversible. TD was increased after 15 minutes. Guanethidine 2 X 10(-3) M initially decreased Vmax and height before causing depolarization. 2. Pretreatment with tetrodotoxin (TTX) 1.6 X 10(-7) M prevented or reversed the initial increases in Vmax, height and TD induced by guanethidine (4 X 10(-4) M). 3 TTX 3.1 to 6.2 X 10(-6) M, added 15 or 30 min after guanethidine 4 X 10(-4) M, delayed or prevented depolarization by guanethidine. 4 Ouabain 10(-5) M incubated for 20 and 90 min greatly inhibited Na+, K+-adenosine triphosphatase and K+-phosphatase activities; guanethidine was without effect. 5 Guanethidine probably increases resting sodium permeability after the promotion of increases in sodium permeability during the AP. High doses of the drug decrease sodium permeability during the AP."}
{"id": "PMID:206305", "title": "Reversal of the action of amino acid antagonists by barbiturates and other hypnotic drugs.", "content": "1 The effects of pentobarbitone (PB) and other sedative/hypnotic drugs have been examined in relation to gamma-aminobutyric acid (GABA) in vitro on the superfused isolated superior cervical ganglion of the rat and in vivo on single units in the brain stem of the anaesthetized rat.2 PB, and other barbiturates, depolarized the ganglion in a dose-dependent manner (threshold concentration 100-300 muM, cf. GABA depolarization threshold 1 muM). The depolarization was reduced in the presence of the selective GABA antagonist (+)-bicuculline methochloride (Bic). Other non-barbiturate sedatives e.g. chlordiazepoxide, amitriptyline, promethazine at concentrations up to 2mM produced no depolarization.3 PB, tested at concentrations up to 80 muM, produced variable effects on the dose-response curve to GABA. On most occasions a slight potentiation occurred in responses to low concentrations of GABA (below 10 muM) coupled with a depression in the responses to concentrations of GABA greater than 10 muM.4 Superfusion with PB in the presence of Bic reversed the depression in the response to GABA produced by Bic. This reversal phenomenon occurred at concentrations of PB too low to depolarize the ganglion and was dependent not only on the concentration of PB but also on that of Bic.5 The reversal potency within an homologous series of barbiturates increased with the size of the alkyl substituent (R2) at C5 on the barbiturate ring. The most potent occurred when the substituent contained 5 carbon atoms (pentobarbitone and amylobarbitone); above this, activity decreased.6 PB reversed the effects of the other GABA antagonists, tetramethylenedisulphotetramine and isopropyl bicyclophosphate and also the non-selective antagonism produced by strychnine. A concomitant reduction by strychnine of responses to the cholinomimetic, carbachol, was not reversed by PB.7 Non-barbiturate sedative/hypnotics also reversed the GABA antagonism produced by Bic. The benzodiazepines were effective at lower concentrations than PB (chlordiazepoxide threshold concentration 0.5 muM, cf. PB 5 muM), however, they only produced a partial reversal even at concentrations much higher than the maximally effective concentration of PB.8 The Bic reversal effect of chloridazepoxide (and other benzodiazepines) lasted many hours after removal from the superfusion solution. By contrast the effect of PB lasted only 15-30 min after its removal.9 Chlordiazepoxide (30 muM) applied in the absence of Bic did not affect the response to GABA but did reduce the depression produced by the subsequent application of Bic even though the chlordiazepoxide had been removed 40 min earlier.10 In the rat brain stem in vivo PB, applied iontophoretically in amounts which neither decreased the spontaneous neuronal firing rate nor affected the response to GABA or glycine, reversed the GABA antagonism induced by iontophoretic application of Bic (in all 23 neurones tested). PB also reversed the antagonism produced by strychnine of responses to glycine although this was less readily observed (5 out of 14 neurones tested).11 Iontophoretic application of other barbiturates and chlordiazepoxide also reversed the effect of Bic. Chlordiazepoxide only produced a partial reversal, as in the isolated ganglion, and no reversal could be demonstrated with flurazepam.12 Intravenous administration of thiopentone (1.3 mg/kg) pentobarbitone (0.4-5.5 mg/kg) hexobarbitone (0.4-0.8 mg/kg) and clonazepam (0.1-0.2 mg/kg) also reversed the effect of iontophoretically applied Bic. The reversal by clonazepam was of much longer duration than that produced by the barbiturates.13 It is suggested that the reversal exhibited by PB and the other hypnotics may be explained by assuming that the amino acids and their antagonists bind to the membrane at separate sites. If the reversal agent has particular affinity only for the antagonist binding site then it may displace the antagonist without affecting the receptor.", "contents": "Reversal of the action of amino acid antagonists by barbiturates and other hypnotic drugs. 1 The effects of pentobarbitone (PB) and other sedative/hypnotic drugs have been examined in relation to gamma-aminobutyric acid (GABA) in vitro on the superfused isolated superior cervical ganglion of the rat and in vivo on single units in the brain stem of the anaesthetized rat.2 PB, and other barbiturates, depolarized the ganglion in a dose-dependent manner (threshold concentration 100-300 muM, cf. GABA depolarization threshold 1 muM). The depolarization was reduced in the presence of the selective GABA antagonist (+)-bicuculline methochloride (Bic). Other non-barbiturate sedatives e.g. chlordiazepoxide, amitriptyline, promethazine at concentrations up to 2mM produced no depolarization.3 PB, tested at concentrations up to 80 muM, produced variable effects on the dose-response curve to GABA. On most occasions a slight potentiation occurred in responses to low concentrations of GABA (below 10 muM) coupled with a depression in the responses to concentrations of GABA greater than 10 muM.4 Superfusion with PB in the presence of Bic reversed the depression in the response to GABA produced by Bic. This reversal phenomenon occurred at concentrations of PB too low to depolarize the ganglion and was dependent not only on the concentration of PB but also on that of Bic.5 The reversal potency within an homologous series of barbiturates increased with the size of the alkyl substituent (R2) at C5 on the barbiturate ring. The most potent occurred when the substituent contained 5 carbon atoms (pentobarbitone and amylobarbitone); above this, activity decreased.6 PB reversed the effects of the other GABA antagonists, tetramethylenedisulphotetramine and isopropyl bicyclophosphate and also the non-selective antagonism produced by strychnine. A concomitant reduction by strychnine of responses to the cholinomimetic, carbachol, was not reversed by PB.7 Non-barbiturate sedative/hypnotics also reversed the GABA antagonism produced by Bic. The benzodiazepines were effective at lower concentrations than PB (chlordiazepoxide threshold concentration 0.5 muM, cf. PB 5 muM), however, they only produced a partial reversal even at concentrations much higher than the maximally effective concentration of PB.8 The Bic reversal effect of chloridazepoxide (and other benzodiazepines) lasted many hours after removal from the superfusion solution. By contrast the effect of PB lasted only 15-30 min after its removal.9 Chlordiazepoxide (30 muM) applied in the absence of Bic did not affect the response to GABA but did reduce the depression produced by the subsequent application of Bic even though the chlordiazepoxide had been removed 40 min earlier.10 In the rat brain stem in vivo PB, applied iontophoretically in amounts which neither decreased the spontaneous neuronal firing rate nor affected the response to GABA or glycine, reversed the GABA antagonism induced by iontophoretic application of Bic (in all 23 neurones tested). PB also reversed the antagonism produced by strychnine of responses to glycine although this was less readily observed (5 out of 14 neurones tested).11 Iontophoretic application of other barbiturates and chlordiazepoxide also reversed the effect of Bic. Chlordiazepoxide only produced a partial reversal, as in the isolated ganglion, and no reversal could be demonstrated with flurazepam.12 Intravenous administration of thiopentone (1.3 mg/kg) pentobarbitone (0.4-5.5 mg/kg) hexobarbitone (0.4-0.8 mg/kg) and clonazepam (0.1-0.2 mg/kg) also reversed the effect of iontophoretically applied Bic. The reversal by clonazepam was of much longer duration than that produced by the barbiturates.13 It is suggested that the reversal exhibited by PB and the other hypnotics may be explained by assuming that the amino acids and their antagonists bind to the membrane at separate sites. If the reversal agent has particular affinity only for the antagonist binding site then it may displace the antagonist without affecting the receptor."}
{"id": "PMID:206306", "title": "Species of differences in postganglionic motor transmission to the retractor penis muscle.", "content": "1 Graded motor responses were elicited in isolated, desheathed, thin strips of dog, horse, pig and sheep retractor penis (RP) muscles by field stimulation with trains of 0.2 ms pulses at 10 hertz. These twitches were shown to be neurogenic in all four species, by their prompt extinction in tetrodotoxin.2 alpha-Adrenoceptor blocking drugs abolished the contractile response to noradrenaline and to tyramine in all four species.3 Motor transmission was wholly adrenergic in the horse as in the dog RP because phentolamine rapidly abolished the electrically induced twitches in both these species; but in the pig and in the sheep RP a large proportion of the motor transmission was unaffected by phentolamine given in many times the concentration required to abolish matching noradrenaline-induced contractions.4 Because of the occurrence of periodic spasms in sheep preparations, further investigation of the phentolamine-resistant transmission was confined to the pig RP. Its responses were shown to be entirely postganglionic in origin because they were unaffected by pentolinium.5 In the pig RP a considerable proportion of the phentolamine-resistant motor transmission persisted after combined blockade of alpha- and beta-adrenoceptors by phenoxybenzamine plus propranolol and was more resistant to guanethidine and bretylium than the motor transmission to the dog RP; it was not extinguished after reserpine treatment.6 The pig RP is contracted by histamine but is rather insensitive to acetylcholine, 5-hydroxytryptamine and adenosine-5'-triphosphate. The motor transmission remained unaffected after responses to these substances were blocked by the following antagonists, given alone or in combination: mepyramine, burimamide, atropine, (+)-tubocurarine, methysergide and 2-2'-pyridylisatogen tosylate.", "contents": "Species of differences in postganglionic motor transmission to the retractor penis muscle. 1 Graded motor responses were elicited in isolated, desheathed, thin strips of dog, horse, pig and sheep retractor penis (RP) muscles by field stimulation with trains of 0.2 ms pulses at 10 hertz. These twitches were shown to be neurogenic in all four species, by their prompt extinction in tetrodotoxin.2 alpha-Adrenoceptor blocking drugs abolished the contractile response to noradrenaline and to tyramine in all four species.3 Motor transmission was wholly adrenergic in the horse as in the dog RP because phentolamine rapidly abolished the electrically induced twitches in both these species; but in the pig and in the sheep RP a large proportion of the motor transmission was unaffected by phentolamine given in many times the concentration required to abolish matching noradrenaline-induced contractions.4 Because of the occurrence of periodic spasms in sheep preparations, further investigation of the phentolamine-resistant transmission was confined to the pig RP. Its responses were shown to be entirely postganglionic in origin because they were unaffected by pentolinium.5 In the pig RP a considerable proportion of the phentolamine-resistant motor transmission persisted after combined blockade of alpha- and beta-adrenoceptors by phenoxybenzamine plus propranolol and was more resistant to guanethidine and bretylium than the motor transmission to the dog RP; it was not extinguished after reserpine treatment.6 The pig RP is contracted by histamine but is rather insensitive to acetylcholine, 5-hydroxytryptamine and adenosine-5'-triphosphate. The motor transmission remained unaffected after responses to these substances were blocked by the following antagonists, given alone or in combination: mepyramine, burimamide, atropine, (+)-tubocurarine, methysergide and 2-2'-pyridylisatogen tosylate."}
{"id": "PMID:206307", "title": "Effects of magnesium on contractile responses induced by electrical transmural stimulation and noradrenaline in rabbit thoracic aorta.", "content": "1 In rabbit isolated thoracic aortae, effects of magnesium ions on the contraction and (3)H-efflux in response to electrical transmural stimulation and on the contractile responses induced by noradrenaline and KCl were investigated.2 Addition of magnesium (1.2, 3.6, 12.0 and 24.0 mM) to the bathing solution inhibited the electrically induced contractions in a dose-related manner; the inhibition was complete with a concentration of 24.0 mM.3 The increase in (3)H-efflux induced by electrical transmural stimulation was inhibited by the addition of magnesium to the superfusing fluid, but a complete block was not obtained even in high concentrations of magnesium.4 Magnesium ions (1.2, 3.6, 12.0 and 24.0 mM) inhibited the contractile responses induced by low concentrations of noradrenaline (2 x 10(-8)M) and KCl (2 x 10(-2)M). However, the responses induced by higher concentrations of noradrenaline (5 x 10(-7) and 10(-5)M) and KCl (3 and 4 x 10(-2)M) were enhanced by low concentrations of magnesium.5 Magnesium ions affect both presynaptic and effector sites in rabbit thoracic aortae but in a different manner; magnesium manifests only an inhibitory effect on noradrenaline release from the adrenergic nerves, but dual effects on reactivity of vascular smooth muscle, depending on concentrations of magnesium and stimulants; it is suggested that the change in vascular reactivity is more important than the reduction in transmitter release when magnesium inhibits the response to nerve stimulation.", "contents": "Effects of magnesium on contractile responses induced by electrical transmural stimulation and noradrenaline in rabbit thoracic aorta. 1 In rabbit isolated thoracic aortae, effects of magnesium ions on the contraction and (3)H-efflux in response to electrical transmural stimulation and on the contractile responses induced by noradrenaline and KCl were investigated.2 Addition of magnesium (1.2, 3.6, 12.0 and 24.0 mM) to the bathing solution inhibited the electrically induced contractions in a dose-related manner; the inhibition was complete with a concentration of 24.0 mM.3 The increase in (3)H-efflux induced by electrical transmural stimulation was inhibited by the addition of magnesium to the superfusing fluid, but a complete block was not obtained even in high concentrations of magnesium.4 Magnesium ions (1.2, 3.6, 12.0 and 24.0 mM) inhibited the contractile responses induced by low concentrations of noradrenaline (2 x 10(-8)M) and KCl (2 x 10(-2)M). However, the responses induced by higher concentrations of noradrenaline (5 x 10(-7) and 10(-5)M) and KCl (3 and 4 x 10(-2)M) were enhanced by low concentrations of magnesium.5 Magnesium ions affect both presynaptic and effector sites in rabbit thoracic aortae but in a different manner; magnesium manifests only an inhibitory effect on noradrenaline release from the adrenergic nerves, but dual effects on reactivity of vascular smooth muscle, depending on concentrations of magnesium and stimulants; it is suggested that the change in vascular reactivity is more important than the reduction in transmitter release when magnesium inhibits the response to nerve stimulation."}
{"id": "PMID:206308", "title": "The neuronal origin of prostaglandin released from the rabbit portal vein in response to electrical stimulation.", "content": "Transmural electrical stimulation of the isolated portal vein of the rabbit was accompanied by the release of a prostaglandin-like substance (PLS). Thin layer chromatography coupled with bioassay indicated that this substance was probably prostaglandin E2 (PGE2). 2 Indomethacin potentiated the response of the portal vein to electrical stimulation at 2 Hz and abolished the release of the PLS. 3 There was no significant change in the amount of PLS released from the portal vein in response to electrical stimulation at 2 Hz when the contractile response of the portal vein was prevented by pretreatment with phentolamine or guanthidine. 4 In vitro denervation of the portal vein with 6-hydroxydopamine or the omission of Ca2+ from the bathing solution caused a significant reduction in the amount of PLS released from the portal vein in response to electrical stimulation at 2 hertz. 5 It is concluded that electrical stimulation of the isolated portal vein of the rabbit is accompanied by the release of a PLS, probably PGE2, from a neuronal source. The synthesis and release of the PLS is Ca2+ -dependent.", "contents": "The neuronal origin of prostaglandin released from the rabbit portal vein in response to electrical stimulation. Transmural electrical stimulation of the isolated portal vein of the rabbit was accompanied by the release of a prostaglandin-like substance (PLS). Thin layer chromatography coupled with bioassay indicated that this substance was probably prostaglandin E2 (PGE2). 2 Indomethacin potentiated the response of the portal vein to electrical stimulation at 2 Hz and abolished the release of the PLS. 3 There was no significant change in the amount of PLS released from the portal vein in response to electrical stimulation at 2 Hz when the contractile response of the portal vein was prevented by pretreatment with phentolamine or guanthidine. 4 In vitro denervation of the portal vein with 6-hydroxydopamine or the omission of Ca2+ from the bathing solution caused a significant reduction in the amount of PLS released from the portal vein in response to electrical stimulation at 2 hertz. 5 It is concluded that electrical stimulation of the isolated portal vein of the rabbit is accompanied by the release of a PLS, probably PGE2, from a neuronal source. The synthesis and release of the PLS is Ca2+ -dependent."}
{"id": "PMID:206309", "title": "Pharmacological and electrophysiological studies of morphine and enkephalin on rat supraspinal neurones and cat spinal neurones.", "content": "1 The actions of morphine, methionine and leucine enkephalin, administered electrophoretically, were studied on supraspinal neurones in the cortex and brainstem of the rat anaesthetized with urethane and on spinal Renshaw cells and dorsal horn interneurones in the cat anaesthetized with pentobarbitone.2 The majority of Renshaw cells and cortical and brainstem neurones were excited by all three compounds although some supraspinal neurones were depressed.3 Naloxone reversibly antagonized both excitatory and depressant actions of morphine and enkephalin. Acetylcholine-induced excitation but not amino acid-induced excitation was also antagonized by naloxone.4 Neither morphine nor the enkephalins had any naloxone-reversible action on dorsal horn neurones when ejected from conventional multibarrelled electrodes. However, morphine but not enkephalin, administered into the substantia gelatinosa region of the spinal cord selectively reduced responses to noxious stimuli of neurones in deeper laminae. Naloxone administered into the same region antagonized this action of morphine.5 Intravenous morphine also antagonized responses of dorsal horn neurones to noxious stimuli and subsequent intravenous naloxone reversed this effect.6 It was concluded that the excitatory and inhibitory effects of morphine and enkephalin on central neurones may be mediated by actions on different opiate receptors and that depression of noxious responses of dorsal horn neurones may be relevant to the analgesic action of morphine.", "contents": "Pharmacological and electrophysiological studies of morphine and enkephalin on rat supraspinal neurones and cat spinal neurones. 1 The actions of morphine, methionine and leucine enkephalin, administered electrophoretically, were studied on supraspinal neurones in the cortex and brainstem of the rat anaesthetized with urethane and on spinal Renshaw cells and dorsal horn interneurones in the cat anaesthetized with pentobarbitone.2 The majority of Renshaw cells and cortical and brainstem neurones were excited by all three compounds although some supraspinal neurones were depressed.3 Naloxone reversibly antagonized both excitatory and depressant actions of morphine and enkephalin. Acetylcholine-induced excitation but not amino acid-induced excitation was also antagonized by naloxone.4 Neither morphine nor the enkephalins had any naloxone-reversible action on dorsal horn neurones when ejected from conventional multibarrelled electrodes. However, morphine but not enkephalin, administered into the substantia gelatinosa region of the spinal cord selectively reduced responses to noxious stimuli of neurones in deeper laminae. Naloxone administered into the same region antagonized this action of morphine.5 Intravenous morphine also antagonized responses of dorsal horn neurones to noxious stimuli and subsequent intravenous naloxone reversed this effect.6 It was concluded that the excitatory and inhibitory effects of morphine and enkephalin on central neurones may be mediated by actions on different opiate receptors and that depression of noxious responses of dorsal horn neurones may be relevant to the analgesic action of morphine."}
{"id": "PMID:206310", "title": "Stimulation of presynaptic beta-adrenoceptors enhances [3H]-noradrenaline release druing nerve stimulation in the perfused cat spleen.", "content": "1 The effects of isoprenaline, propranolol and phosphodiesterase inhibitors on (3)H-transmitter overflow elicited by low frequency nerve stimulation were determined in the isolated perfused spleen of the cat.2 (-)-Isoprenaline (0.14, 1.4, and 14 nM) produced a concentration-dependent increase in [(3)H]-transmitter overflow evoked by nerve stimulation at 1 Hz and was more effective at 1 Hz than at 2 hertz.3 A concentration of propranolol (0.1 muM), devoid of neurone blocking activity, blocked this effect of (-)-isoprenaline. These results are compatible with the presence of beta-adrenoceptors in the noradrenergic nerve endings of the cat spleen.4 (+)-Isoprenaline (140 nM) failed to increase the release of radioactivity induced by nerve stimulation, indicating that the beta-adrenoceptor mediating the facilitation of transmitter release was stereospecific.5 The increase in (3)H-transmitter overflow induced by nerve stimulation during exposure to the phosphodiesterase inhibitor, papaverine (27 muM) was more pronounced than that obtained in the presence of 3-isobutyl-1-methyl xanthine (IBMX) 0.5 mM. The facilitation in transmitter release induced by papaverine was not correlated with the granular effect produced by this drug.6 In the presence of papaverine, the concentration-effect curve for (-)-isoprenaline on transmitter release was shifted to the left and its maximum was increased. In addition, propranolol significantly reduced the enhancement in noradrenaline release obtained by exposure to papaverine under conditions in which the granular effect produced by the phosphodiesterase inhibitor was even greater than in the absence of the beta-blocker.7 It is concluded that activation of presynaptic beta-adrenoceptors in the perfused cat spleen leads to an enhancement in transmitter release which appears to be linked to an increase in cyclic adenosine 3',5'-monophosphate levels in noradrenergic nerve endings.", "contents": "Stimulation of presynaptic beta-adrenoceptors enhances [3H]-noradrenaline release druing nerve stimulation in the perfused cat spleen. 1 The effects of isoprenaline, propranolol and phosphodiesterase inhibitors on (3)H-transmitter overflow elicited by low frequency nerve stimulation were determined in the isolated perfused spleen of the cat.2 (-)-Isoprenaline (0.14, 1.4, and 14 nM) produced a concentration-dependent increase in [(3)H]-transmitter overflow evoked by nerve stimulation at 1 Hz and was more effective at 1 Hz than at 2 hertz.3 A concentration of propranolol (0.1 muM), devoid of neurone blocking activity, blocked this effect of (-)-isoprenaline. These results are compatible with the presence of beta-adrenoceptors in the noradrenergic nerve endings of the cat spleen.4 (+)-Isoprenaline (140 nM) failed to increase the release of radioactivity induced by nerve stimulation, indicating that the beta-adrenoceptor mediating the facilitation of transmitter release was stereospecific.5 The increase in (3)H-transmitter overflow induced by nerve stimulation during exposure to the phosphodiesterase inhibitor, papaverine (27 muM) was more pronounced than that obtained in the presence of 3-isobutyl-1-methyl xanthine (IBMX) 0.5 mM. The facilitation in transmitter release induced by papaverine was not correlated with the granular effect produced by this drug.6 In the presence of papaverine, the concentration-effect curve for (-)-isoprenaline on transmitter release was shifted to the left and its maximum was increased. In addition, propranolol significantly reduced the enhancement in noradrenaline release obtained by exposure to papaverine under conditions in which the granular effect produced by the phosphodiesterase inhibitor was even greater than in the absence of the beta-blocker.7 It is concluded that activation of presynaptic beta-adrenoceptors in the perfused cat spleen leads to an enhancement in transmitter release which appears to be linked to an increase in cyclic adenosine 3',5'-monophosphate levels in noradrenergic nerve endings."}
{"id": "PMID:206311", "title": "Hepatocellular carcinoma associated with oral contraceptives.", "content": "A primary hepatic tumour occurred in a 36-year-old woman who had been taking oral contraceptives for 6 years; she was treated by partial hepatectomy. The neoplasm had the characteristics of a well-differentiated hepatocellular carcinoma and the regional lymph nodes contained similar tumour.", "contents": "Hepatocellular carcinoma associated with oral contraceptives. A primary hepatic tumour occurred in a 36-year-old woman who had been taking oral contraceptives for 6 years; she was treated by partial hepatectomy. The neoplasm had the characteristics of a well-differentiated hepatocellular carcinoma and the regional lymph nodes contained similar tumour."}
{"id": "PMID:206312", "title": "The effect of age and lung pathology on cytochrome a,a3 redox levels in rat cerebral cortex.", "content": "The steady-state reduction/oxidation (redox) ratio of cytochrome a,a3 in the non-stressed or 'resting' cerebral cortex was compared in 'healthy' mature and aged rats and in animals with varying degrees of lung pathology present. By using noninvasive dual wavelength spectrophotometry, cytochrome a,a3 was found to be approximately 30% reduced under 'resting' conditions in both mature and 'aged' brain. Although no significant age-related or strain differences were apparent, the 'resting' redox level of cytochrome a,a3 was markedly affected by the presence of lung pathology. The redox ratio was lower in animals where lung lesion involvement was not extensive, and higher (indicative or cellular hypoxia) in animals having both extensive acute and chronic lung pathology. These studies demonstate that, regardless of age or lung pathology, the cortical cytochrome a,a3 redox state is labile to changes in the amount of inspired oxygen, a condition differing from that of isolated mitochondria. These results indicate that dysfunction of the mitochondrial respiratory chain is not a direct or primary consequence of chronlogical aging in the 'resting' brain.", "contents": "The effect of age and lung pathology on cytochrome a,a3 redox levels in rat cerebral cortex. The steady-state reduction/oxidation (redox) ratio of cytochrome a,a3 in the non-stressed or 'resting' cerebral cortex was compared in 'healthy' mature and aged rats and in animals with varying degrees of lung pathology present. By using noninvasive dual wavelength spectrophotometry, cytochrome a,a3 was found to be approximately 30% reduced under 'resting' conditions in both mature and 'aged' brain. Although no significant age-related or strain differences were apparent, the 'resting' redox level of cytochrome a,a3 was markedly affected by the presence of lung pathology. The redox ratio was lower in animals where lung lesion involvement was not extensive, and higher (indicative or cellular hypoxia) in animals having both extensive acute and chronic lung pathology. These studies demonstate that, regardless of age or lung pathology, the cortical cytochrome a,a3 redox state is labile to changes in the amount of inspired oxygen, a condition differing from that of isolated mitochondria. These results indicate that dysfunction of the mitochondrial respiratory chain is not a direct or primary consequence of chronlogical aging in the 'resting' brain."}
{"id": "PMID:206314", "title": "Formation of synapses between cells of a neuroblastoma X glioma hybrid clone and mouse myotubes.", "content": "Synapses form between cells of a neuroblastoma X glioma hybrid clone and cultured mouse skeletal myotubes. The synapses are cholinergic, and the acetylcholine release mechanism is dependent on calcium ions. The transmitter output of the synapses is low, with considerable variability in the latency and amplitude of the postsynaptic responses to presynaptic action potentials. The fine structure of physiologically identified functional junctions was examined electron microscopically. Small (50 nm) clear vesicles were seen presynaptically and there were areas with a wide (approx. 50 nm) gap containing basement membrane-like material between the pre- and postsynaptic cells. In addition, in some regions there was a densely staining material lining the muscle membrane and some suggestion of infolding of the muscle membrane. In none of the cases, however, have areas been found where small, clear vesicles cluster around pre- and postsynaptic membrane densities. Thus, functional synapses can occur in the absence of the highly organized synaptic structure seen at mature synapses.", "contents": "Formation of synapses between cells of a neuroblastoma X glioma hybrid clone and mouse myotubes. Synapses form between cells of a neuroblastoma X glioma hybrid clone and cultured mouse skeletal myotubes. The synapses are cholinergic, and the acetylcholine release mechanism is dependent on calcium ions. The transmitter output of the synapses is low, with considerable variability in the latency and amplitude of the postsynaptic responses to presynaptic action potentials. The fine structure of physiologically identified functional junctions was examined electron microscopically. Small (50 nm) clear vesicles were seen presynaptically and there were areas with a wide (approx. 50 nm) gap containing basement membrane-like material between the pre- and postsynaptic cells. In addition, in some regions there was a densely staining material lining the muscle membrane and some suggestion of infolding of the muscle membrane. In none of the cases, however, have areas been found where small, clear vesicles cluster around pre- and postsynaptic membrane densities. Thus, functional synapses can occur in the absence of the highly organized synaptic structure seen at mature synapses."}
{"id": "PMID:206315", "title": "Epileptic properties of leucine- and methionine-enkephalin: comparison with morphine and reversibility by naloxone.", "content": "Morphologically similar epileptic seizures were recorded from the cortex of rats after injections into the lateral ventricle of 100 microgram of leucine-enkephalin, methionine-enkephalin, and morphine. Seizures were either greatly attenuated or blocked completely by prior systemic administration of naloxone (10 mg/kg). These findings suggest that such seizures result from an interaction of these compounds with opiate receptors in the brain. The epileptogenic potency of the enkephalins was illustrated by the observation that seizures and other pathological manifestations could still be elicited by doses as low as 10 microgram. Leucine-enkephalin was seen to have greater epiliptic potency than methionine-enkephalin. At doses of 1 microgram both enkephalins typically evoked cortical spindles resembling those seen in drowsy animals. Enkephalin-induced analgesia was seen in only one animal at the 100 microgram dose. Results obtained with repeated injections of morphine suggest that the epileptogenic effect of opiates may be subject to either tolerance or potentiation, depending on the prior occurrence of seizures. A synthesis of the present findings with several other lines of evidence suggests both that endogenous enkephalins play some role in normal mechanisms of reward, and that, when regulatory processes are disturbed, they may contribute as well to the elaboration of certain epileptic phenomena.", "contents": "Epileptic properties of leucine- and methionine-enkephalin: comparison with morphine and reversibility by naloxone. Morphologically similar epileptic seizures were recorded from the cortex of rats after injections into the lateral ventricle of 100 microgram of leucine-enkephalin, methionine-enkephalin, and morphine. Seizures were either greatly attenuated or blocked completely by prior systemic administration of naloxone (10 mg/kg). These findings suggest that such seizures result from an interaction of these compounds with opiate receptors in the brain. The epileptogenic potency of the enkephalins was illustrated by the observation that seizures and other pathological manifestations could still be elicited by doses as low as 10 microgram. Leucine-enkephalin was seen to have greater epiliptic potency than methionine-enkephalin. At doses of 1 microgram both enkephalins typically evoked cortical spindles resembling those seen in drowsy animals. Enkephalin-induced analgesia was seen in only one animal at the 100 microgram dose. Results obtained with repeated injections of morphine suggest that the epileptogenic effect of opiates may be subject to either tolerance or potentiation, depending on the prior occurrence of seizures. A synthesis of the present findings with several other lines of evidence suggests both that endogenous enkephalins play some role in normal mechanisms of reward, and that, when regulatory processes are disturbed, they may contribute as well to the elaboration of certain epileptic phenomena."}
{"id": "PMID:206316", "title": "Isolation and partial characterization of rat CNS axolemma enriched fractions.", "content": "Axolemma-enriched fractions were prepared from rat brain by osmotic shock of a purified preparation of myelinated axons and subsequent separation of myelin, two axolemma-enriched fractions and myelin-free axons by density gradient centrifugation. Compared with the starting whole homogenate, the fractions were enriched in specific activity of Na+K+ ATPase, acetylcholinesterase, 5'nucleotidase as well as 2',3'-cyclic nucleotide 3'phosphohydrolase. Compared with myelin, the axolemmal fractions are greatly enriched in high molecular weight proteins. The 1.0/1.2 fraction has a predominant peak of fucose-labeled glycoprotein with a molecular weight between that of the myelin associated glycoprotein and the Wolfgram protein which is absent from the myelin glycoprotein profile. Polyacrylamide gel electrophoresis showed that the protein profile of myelin isolated by this procedure was similar to that of myelin isolated by other procedures and that the myelin specific basic and proteolipid proteins were virtually absent in the axolemma-enriched fractions. Both axolemma fractions were enriched in higher MW proteins, some of which resembled proteins in the myelin protein profile. Both axolemma-enriched fractions specifically bind between 2 and 3 pmoles of [3H]tetrodotoxin per mg protein. The axolemma-enriched fractions incorporated [3H]leucine and [14C]fucose exclusively into high molecular weight proteins and glycoproteins. In contrast myelin concomitantly isolated with the axolemma-enriched fractions had a significant amount of [3H]leucine labeled protein in myelin proteolipid and basic proteins. In addition to the myelin associated g-ycoprotein the [14C]fucose labeled a glycoprotein of slightly larger apparent molecular weight than proteolipid protein was found in the myelin fraction while the comparable labeled glycoprotein was absent in the axolemma-enriched fractions. The possible extent of contamination of these fractions by myelin or myelin subfractions and relationship of these axolemma-enriched fractions to other axolemma preparations are discussed.", "contents": "Isolation and partial characterization of rat CNS axolemma enriched fractions. Axolemma-enriched fractions were prepared from rat brain by osmotic shock of a purified preparation of myelinated axons and subsequent separation of myelin, two axolemma-enriched fractions and myelin-free axons by density gradient centrifugation. Compared with the starting whole homogenate, the fractions were enriched in specific activity of Na+K+ ATPase, acetylcholinesterase, 5'nucleotidase as well as 2',3'-cyclic nucleotide 3'phosphohydrolase. Compared with myelin, the axolemmal fractions are greatly enriched in high molecular weight proteins. The 1.0/1.2 fraction has a predominant peak of fucose-labeled glycoprotein with a molecular weight between that of the myelin associated glycoprotein and the Wolfgram protein which is absent from the myelin glycoprotein profile. Polyacrylamide gel electrophoresis showed that the protein profile of myelin isolated by this procedure was similar to that of myelin isolated by other procedures and that the myelin specific basic and proteolipid proteins were virtually absent in the axolemma-enriched fractions. Both axolemma fractions were enriched in higher MW proteins, some of which resembled proteins in the myelin protein profile. Both axolemma-enriched fractions specifically bind between 2 and 3 pmoles of [3H]tetrodotoxin per mg protein. The axolemma-enriched fractions incorporated [3H]leucine and [14C]fucose exclusively into high molecular weight proteins and glycoproteins. In contrast myelin concomitantly isolated with the axolemma-enriched fractions had a significant amount of [3H]leucine labeled protein in myelin proteolipid and basic proteins. In addition to the myelin associated g-ycoprotein the [14C]fucose labeled a glycoprotein of slightly larger apparent molecular weight than proteolipid protein was found in the myelin fraction while the comparable labeled glycoprotein was absent in the axolemma-enriched fractions. The possible extent of contamination of these fractions by myelin or myelin subfractions and relationship of these axolemma-enriched fractions to other axolemma preparations are discussed."}
{"id": "PMID:206321", "title": "The influx of pyrophosphate ions into calvaria in vitro.", "content": "The flux of 32P-labeled inorganic pyrophosphate (PPi) into bone was studied in vitro using Ussing chamber techniques and calvaria from newborn rat pups. Because insignificant hydrolysis and backflux of PPi took place under experimental conditions, it was possible to study the penetration of bone membranes by PP1 unambiguously. At physiological concentrations, the influx was found to be linearly concentration dependent and to follow first order kinetics, apparently a simple diffusion process. In magnitude, the intrinsic constant for influx was found to be approximately one-half that of inorganic phosphate ions under comparable conditions.", "contents": "The influx of pyrophosphate ions into calvaria in vitro. The flux of 32P-labeled inorganic pyrophosphate (PPi) into bone was studied in vitro using Ussing chamber techniques and calvaria from newborn rat pups. Because insignificant hydrolysis and backflux of PPi took place under experimental conditions, it was possible to study the penetration of bone membranes by PP1 unambiguously. At physiological concentrations, the influx was found to be linearly concentration dependent and to follow first order kinetics, apparently a simple diffusion process. In magnitude, the intrinsic constant for influx was found to be approximately one-half that of inorganic phosphate ions under comparable conditions."}
{"id": "PMID:206322", "title": "Radiogenic free radicals as molecular probes in bone.", "content": "Exposure of bone mineral to X-rays generates free radicals. These are usually very labile, but can be stabilized at liquid nitrogen temperatures for study by electron spin resonance spectroscopy. The free radicals thus detected in the present study included one with resonances arising from an electron excess center and 2 species with electron-deficit centers: a phosphate anion radical and a radical associated with carbonate. Each of these radicals seemed to be located chiefly at the mineral surface and was sensitive to the surface environment. Presence of an organic phase, as in whole bone, modified free radical production in a manner that suggests interference with the formation of electron deficit centers. Comparison with other synthetic minerals suggests that precipitated carbonate-apatites are good models for bone mineral.", "contents": "Radiogenic free radicals as molecular probes in bone. Exposure of bone mineral to X-rays generates free radicals. These are usually very labile, but can be stabilized at liquid nitrogen temperatures for study by electron spin resonance spectroscopy. The free radicals thus detected in the present study included one with resonances arising from an electron excess center and 2 species with electron-deficit centers: a phosphate anion radical and a radical associated with carbonate. Each of these radicals seemed to be located chiefly at the mineral surface and was sensitive to the surface environment. Presence of an organic phase, as in whole bone, modified free radical production in a manner that suggests interference with the formation of electron deficit centers. Comparison with other synthetic minerals suggests that precipitated carbonate-apatites are good models for bone mineral."}
{"id": "PMID:206319", "title": "Differential behavioral effects of ACTH 4-10 and [D-Phe7] ACTH 4-10.", "content": "Intraventricular administration of an access of ACTH 4-10 does not interfere with the excessive grooming behavior of rats, elicited by intraventricular administration of [D-Phe7] ACTH 4-10. In an avoidance extinction paradigm, the two ACTH analogs have opposite effects. ACTH 4-10 counteracts the facilitation of extinction seen after [D-Phe7] ACTH 4-10, only under conditions that treatment with ACTH 4-10 alone results in retardation of that extinction. The data are discussed in terms of a multiple interaction of these peptides with brain function.", "contents": "Differential behavioral effects of ACTH 4-10 and [D-Phe7] ACTH 4-10. Intraventricular administration of an access of ACTH 4-10 does not interfere with the excessive grooming behavior of rats, elicited by intraventricular administration of [D-Phe7] ACTH 4-10. In an avoidance extinction paradigm, the two ACTH analogs have opposite effects. ACTH 4-10 counteracts the facilitation of extinction seen after [D-Phe7] ACTH 4-10, only under conditions that treatment with ACTH 4-10 alone results in retardation of that extinction. The data are discussed in terms of a multiple interaction of these peptides with brain function."}
{"id": "PMID:206323", "title": "Paramagnetic and crystallographic effects of low temperature ashing on human bone and tooth enamel.", "content": "Low temperature ashing by excited gas (LTA) causes crystallographic and paramagnetic alterations of the human bone and tooth enamel mineral. On the one hand, LTA induces variations of the alpha lattice parameter. These variations depend upon the nature of the gas used, but are little affected by its degree of excitation. Trapping of gas molecules in the crystal structure is demonstrated. On the other hand, LTA produces two preponderant paramagnetic centers in bone and enamel samples at 20 degrees C. Their inorganic origin clearly indicated. One of the two radicals has been identified as O3- (g1 = 2.002, g2 = 2.010, g3 = 2.016) and the other as (CO3-3 (parallel = 1.996, g = perpendicular 2.003). Variations of the alpha lattice parameter and trapping of paramagnetic gas species do not seem to be directly related.", "contents": "Paramagnetic and crystallographic effects of low temperature ashing on human bone and tooth enamel. Low temperature ashing by excited gas (LTA) causes crystallographic and paramagnetic alterations of the human bone and tooth enamel mineral. On the one hand, LTA induces variations of the alpha lattice parameter. These variations depend upon the nature of the gas used, but are little affected by its degree of excitation. Trapping of gas molecules in the crystal structure is demonstrated. On the other hand, LTA produces two preponderant paramagnetic centers in bone and enamel samples at 20 degrees C. Their inorganic origin clearly indicated. One of the two radicals has been identified as O3- (g1 = 2.002, g2 = 2.010, g3 = 2.016) and the other as (CO3-3 (parallel = 1.996, g = perpendicular 2.003). Variations of the alpha lattice parameter and trapping of paramagnetic gas species do not seem to be directly related."}
{"id": "PMID:206324", "title": "Some comparative properties and localization of porcine jejunal adenylate cyclase.", "content": "Cholera toxin is thought to cause intestinal secretion by activating adenylate cyclase and increasing intracellular 3',5'-cyclic AMP concentrations in intestinal mucosa. Cholera toxin causes profuse secretion of fluid into ligated intestinal loops of both pigs and rabbits, but cholera toxin-induced increases in 3',5'-cyclic AMP concentration are much lower in the pig than in the rabbit. Porcine jejunal adenylate cyclase was examined for unusual properties which might account for a lack of 3'-5'-cyclic AMP accumulation after treatment with cholera toxin. The divalent cation requirements, the pH optimum, and the stimulation by fluoride ion were unremarkable. The Km for ATP was 0.11 mM with negative cooperativity indicated by a Hill coefficient of 0.83. Triton X-100 was inhibitory and guanosine diphosphate methylenephosphate stimulated enzyme activity. Adenylate cyclase activity was highest in the basal and lateral membrane fractions of jejunal mucosa and relatively low in brush-border preparations. Pretreatment of pig jejunum with cholera toxin caused a 30-40% activation of the crude and of the partly purified enzyme. A relatively low activation of adenylase cyclase in pig jejunal mucosa, compared with rabbit, may account for the absence of 3',5'-cyclic AMP accumulation after cholera-toxin treatment in the pig.", "contents": "Some comparative properties and localization of porcine jejunal adenylate cyclase. Cholera toxin is thought to cause intestinal secretion by activating adenylate cyclase and increasing intracellular 3',5'-cyclic AMP concentrations in intestinal mucosa. Cholera toxin causes profuse secretion of fluid into ligated intestinal loops of both pigs and rabbits, but cholera toxin-induced increases in 3',5'-cyclic AMP concentration are much lower in the pig than in the rabbit. Porcine jejunal adenylate cyclase was examined for unusual properties which might account for a lack of 3'-5'-cyclic AMP accumulation after treatment with cholera toxin. The divalent cation requirements, the pH optimum, and the stimulation by fluoride ion were unremarkable. The Km for ATP was 0.11 mM with negative cooperativity indicated by a Hill coefficient of 0.83. Triton X-100 was inhibitory and guanosine diphosphate methylenephosphate stimulated enzyme activity. Adenylate cyclase activity was highest in the basal and lateral membrane fractions of jejunal mucosa and relatively low in brush-border preparations. Pretreatment of pig jejunum with cholera toxin caused a 30-40% activation of the crude and of the partly purified enzyme. A relatively low activation of adenylase cyclase in pig jejunal mucosa, compared with rabbit, may account for the absence of 3',5'-cyclic AMP accumulation after cholera-toxin treatment in the pig."}
{"id": "PMID:206325", "title": "Lapine rotavirus: preliminary studies on epizoology and transmission.", "content": "Antibody to rotavirus was found in sera of domestic rabbits, wild cottontail rabbits and Snowshoe hares. Eight out of 187 stools from a rabbitry contained rotavirus, though no clinical symptoms were apparent. The virus extracted from one such stool infected a five week old seronegative rabbit and led to distention and congestion of the colon, excretion of virus in the stool and a serological response to virus. Human and Simian rotaviruses did not replicate in the rabbits.", "contents": "Lapine rotavirus: preliminary studies on epizoology and transmission. Antibody to rotavirus was found in sera of domestic rabbits, wild cottontail rabbits and Snowshoe hares. Eight out of 187 stools from a rabbitry contained rotavirus, though no clinical symptoms were apparent. The virus extracted from one such stool infected a five week old seronegative rabbit and led to distention and congestion of the colon, excretion of virus in the stool and a serological response to virus. Human and Simian rotaviruses did not replicate in the rabbits."}
{"id": "PMID:206326", "title": "Characteristics of neonatal calf diarrhea virus ribonucleic acid.", "content": "The nucleic acids of neonatal calf diarrhea virus were characterized by isopycnic centrifugation in Cs2SO4, electron microscopy, ultraviolet absorbance temperature profiles and polyacrylamide gel electrophoresis. These studies indicated that the neonatal calf diarrhea virus genome consists of 11 segments of double stranded RNA with a total molecular weight of 10.75 million daltons.", "contents": "Characteristics of neonatal calf diarrhea virus ribonucleic acid. The nucleic acids of neonatal calf diarrhea virus were characterized by isopycnic centrifugation in Cs2SO4, electron microscopy, ultraviolet absorbance temperature profiles and polyacrylamide gel electrophoresis. These studies indicated that the neonatal calf diarrhea virus genome consists of 11 segments of double stranded RNA with a total molecular weight of 10.75 million daltons."}
{"id": "PMID:206327", "title": "Sensitivity and specificity of the fluorescent antibody technique for detection of infectious laryngotracheitis virus.", "content": "The specificity of a fluorescent conjugate to infectious laryngotracheitis virus was examined using chick trachea organ culture or tissue sections infected with other avian viruses (adenovirus, infectious bronchitis, poxvirus, reovirus, Newcastle disease virus, Marek's disease virus, avian encephalomyelitis and infectious bursal agent) or Mycoplasma gallisepticum. Confirmation of virus replication in these preparations was obtained by either 1) demonstration of virus titre increase or 2) demonstration of fluorescence when using the homologous conjugate. Once either of these criteria had been satisfied, negative results with the infectious laryngotracheitis conjugate were taken to indicate that the conjugate would not present false positive results in differentiated cells infected with these heterologous viruses. The spectrum of reactivity of the infectious laryngotracheitis conjugate was then examined on organ cultures infected with several infectious laryngotracheitis isolates from across Canada. Finally, the conjugate was applied to experimental and natural cases of infectious laryngotracheitis and its efficiency was compared to routine virus isolation methods.", "contents": "Sensitivity and specificity of the fluorescent antibody technique for detection of infectious laryngotracheitis virus. The specificity of a fluorescent conjugate to infectious laryngotracheitis virus was examined using chick trachea organ culture or tissue sections infected with other avian viruses (adenovirus, infectious bronchitis, poxvirus, reovirus, Newcastle disease virus, Marek's disease virus, avian encephalomyelitis and infectious bursal agent) or Mycoplasma gallisepticum. Confirmation of virus replication in these preparations was obtained by either 1) demonstration of virus titre increase or 2) demonstration of fluorescence when using the homologous conjugate. Once either of these criteria had been satisfied, negative results with the infectious laryngotracheitis conjugate were taken to indicate that the conjugate would not present false positive results in differentiated cells infected with these heterologous viruses. The spectrum of reactivity of the infectious laryngotracheitis conjugate was then examined on organ cultures infected with several infectious laryngotracheitis isolates from across Canada. Finally, the conjugate was applied to experimental and natural cases of infectious laryngotracheitis and its efficiency was compared to routine virus isolation methods."}
{"id": "PMID:206328", "title": "Polyphosphate-deficient mutants of Anacystis nidulans.", "content": "Polyphosphate-deficient mutants of Anacystis nidulans have been isolated by either ethyl methanesulfonate (EMS) or N-methyl nitrosoguanidine (NTG) mutagenesis and penicillin-enrichment techniques. Mutagenised stock was preincubated in a medium lacking sulfate, then transferred to a phosphate-lacking medium before penicillin treatment. Many single-colony isolates, in contrast to wild-type, show little growth in absence of phosphate, and have altered polyphosphate, and have altered polyphosphate kinase levels indicating that the lesions affect either the activity or the expression of this enzyme. In these same mutants radioactive phosphate incorporation is severely retarded. Electron micrographs confirm the absence of polyphosphate granules in some mutants.", "contents": "Polyphosphate-deficient mutants of Anacystis nidulans. Polyphosphate-deficient mutants of Anacystis nidulans have been isolated by either ethyl methanesulfonate (EMS) or N-methyl nitrosoguanidine (NTG) mutagenesis and penicillin-enrichment techniques. Mutagenised stock was preincubated in a medium lacking sulfate, then transferred to a phosphate-lacking medium before penicillin treatment. Many single-colony isolates, in contrast to wild-type, show little growth in absence of phosphate, and have altered polyphosphate, and have altered polyphosphate kinase levels indicating that the lesions affect either the activity or the expression of this enzyme. In these same mutants radioactive phosphate incorporation is severely retarded. Electron micrographs confirm the absence of polyphosphate granules in some mutants."}
{"id": "PMID:206329", "title": "Growth of Escherichia coli on glucosamine 6-phosphate: selection of a constitutive hexose phosphate transport system mutant.", "content": "Glucosamine 6-phosphate was found to be a substrate but not an inducer for the hexose phosphate transport system of Escherichia coli. Wild-type cells grow very poorly on glucosamine 6-phosphate. A mutant was selected that will grow rapidly on glucosamine 6-phosphate because it contains a constitutive hexose phosphate transport system.", "contents": "Growth of Escherichia coli on glucosamine 6-phosphate: selection of a constitutive hexose phosphate transport system mutant. Glucosamine 6-phosphate was found to be a substrate but not an inducer for the hexose phosphate transport system of Escherichia coli. Wild-type cells grow very poorly on glucosamine 6-phosphate. A mutant was selected that will grow rapidly on glucosamine 6-phosphate because it contains a constitutive hexose phosphate transport system."}
{"id": "PMID:206330", "title": "Purification and some properties of the citrate synthase from a marine Pseudomonas.", "content": "Citrate synthase (citrate-oxaloacetate lyase (CoA acetylating), EC 4.1.3.7) has been purified to electrophoretic homogeneity from a marine Pseudomonas. The enzyme was made up of identical subunits, with a molecular wieght of about 53 000, as determined by sodium dodecyl sulphate - polyacrylamide gel electrophoresis. The native enzyme (citrate synthase II, CS II) could be dissociated by dialysis against 20 mM phosphate (Pi), pH 7; the enzyme thus obtained (citrate synthase I, CS I) was still active, but presented different molecular weight and kinetic and regulatory properties. CS II was activated by adenosine monophosphate (AMP), Pi, and KCl, and inhibited by reduced nicotinamide adenine dinucleotide (NADH), being apparently insensitive to adenosine triphosphate (ATP) and adenosine diphosphate (ADP). The inhibition by NADH was completely counteracted by 0.1 mM AMP, but not by 50 mM Pi or 0.1 M KCl. The activation by KCl and Pi, or by KCl and AMP was nearly additive, whereas that by AMP and Pi was not. The activators acted essentially by increasing Vmax, although they also caused a decrease in the Km values. CS I was inhibited by ATP, ADP, AMP, and KCl, and was insensitive to NADH. CS I could be reassociated after elimination of Pi by dialysis, regaining the higher molecular weight and the activation by AMP characteristic of CS II.", "contents": "Purification and some properties of the citrate synthase from a marine Pseudomonas. Citrate synthase (citrate-oxaloacetate lyase (CoA acetylating), EC 4.1.3.7) has been purified to electrophoretic homogeneity from a marine Pseudomonas. The enzyme was made up of identical subunits, with a molecular wieght of about 53 000, as determined by sodium dodecyl sulphate - polyacrylamide gel electrophoresis. The native enzyme (citrate synthase II, CS II) could be dissociated by dialysis against 20 mM phosphate (Pi), pH 7; the enzyme thus obtained (citrate synthase I, CS I) was still active, but presented different molecular weight and kinetic and regulatory properties. CS II was activated by adenosine monophosphate (AMP), Pi, and KCl, and inhibited by reduced nicotinamide adenine dinucleotide (NADH), being apparently insensitive to adenosine triphosphate (ATP) and adenosine diphosphate (ADP). The inhibition by NADH was completely counteracted by 0.1 mM AMP, but not by 50 mM Pi or 0.1 M KCl. The activation by KCl and Pi, or by KCl and AMP was nearly additive, whereas that by AMP and Pi was not. The activators acted essentially by increasing Vmax, although they also caused a decrease in the Km values. CS I was inhibited by ATP, ADP, AMP, and KCl, and was insensitive to NADH. CS I could be reassociated after elimination of Pi by dialysis, regaining the higher molecular weight and the activation by AMP characteristic of CS II."}
{"id": "PMID:206331", "title": "Direct observation of fungal aggregates in sand dune soil.", "content": "The mycorrhizal fungus Glomerus in association with bean hosts, Phaseolus vulgaris L., growing in pot cultures and grass hosts, Calamovilfa longiflora (Hook). Scribn and Andropogon sp. growing on Lake Huron sand dunes produced extensive external mycelium. This mycelium was the dominant factor in the aggregation of soil particles. Light and scanning electron microscope studies indicated that the sand grains were attached to the hyphae. An amorphous deposit was often present at the interfaces of sand grains and hyphae. It appeared to act as an adhesive. Staining procedures indicated that this material contained polysaccharide. Other microogranisms were observed in association with the Glomus hyphae and the amorphous deposits.", "contents": "Direct observation of fungal aggregates in sand dune soil. The mycorrhizal fungus Glomerus in association with bean hosts, Phaseolus vulgaris L., growing in pot cultures and grass hosts, Calamovilfa longiflora (Hook). Scribn and Andropogon sp. growing on Lake Huron sand dunes produced extensive external mycelium. This mycelium was the dominant factor in the aggregation of soil particles. Light and scanning electron microscope studies indicated that the sand grains were attached to the hyphae. An amorphous deposit was often present at the interfaces of sand grains and hyphae. It appeared to act as an adhesive. Staining procedures indicated that this material contained polysaccharide. Other microogranisms were observed in association with the Glomus hyphae and the amorphous deposits."}
{"id": "PMID:206332", "title": "Plasma lipids and lipoproteins in Friedreich's ataxia and familial spastic ataxia--evidence for an abnormal composition of high density lipoproteins.", "content": "A systematic study of plasma lipids and lipoproteins was carried out in 11 cases of Friedreich's ataxia and 6 cases of familial spastic ataxia (Charlevoix-Saguenay disease) using 11 healthy normolipidemic volunteers of comparable age and sex as controls. No differences were noted in the fatty acid profile of the total lipid fraction, in the total cholesterol and phospholipids or in the percentage distribution of the individual phospholipid classes. The triglycerides were significantly higher in Friedreich's ataxia, but remained within the normal range. Although no systematic abnormalities could be detected in the electrophoretic pattern of plasma lipoproteins or in the apolipoprotein profile on polyacrylamide gel electrophoresis, major differences were found in the high density lipoprotein (HDL) fraction. Their total amount was reduced and their composition was abnormal in both neurological diseases. In Friedreich patients, the relative proportion of cholesterol and triglycerides was increased while the relative protein content was greatly reduced. In Charlevoix disease, a similar abnormality was seen except for the excess of triglycerides. The proportion of phospholipids in HDL was the same in the three groups of patients. In addition, the low density lipoprotein (LDL) fraction was slightly reduced in both diseases. This anomaly of the HDL fraction could indicate that the HDL apolipoprotein moiety has a greater affinity for cholesterol and triglycerides in Friedreich's ataxia than its normal counterpart.", "contents": "Plasma lipids and lipoproteins in Friedreich's ataxia and familial spastic ataxia--evidence for an abnormal composition of high density lipoproteins. A systematic study of plasma lipids and lipoproteins was carried out in 11 cases of Friedreich's ataxia and 6 cases of familial spastic ataxia (Charlevoix-Saguenay disease) using 11 healthy normolipidemic volunteers of comparable age and sex as controls. No differences were noted in the fatty acid profile of the total lipid fraction, in the total cholesterol and phospholipids or in the percentage distribution of the individual phospholipid classes. The triglycerides were significantly higher in Friedreich's ataxia, but remained within the normal range. Although no systematic abnormalities could be detected in the electrophoretic pattern of plasma lipoproteins or in the apolipoprotein profile on polyacrylamide gel electrophoresis, major differences were found in the high density lipoprotein (HDL) fraction. Their total amount was reduced and their composition was abnormal in both neurological diseases. In Friedreich patients, the relative proportion of cholesterol and triglycerides was increased while the relative protein content was greatly reduced. In Charlevoix disease, a similar abnormality was seen except for the excess of triglycerides. The proportion of phospholipids in HDL was the same in the three groups of patients. In addition, the low density lipoprotein (LDL) fraction was slightly reduced in both diseases. This anomaly of the HDL fraction could indicate that the HDL apolipoprotein moiety has a greater affinity for cholesterol and triglycerides in Friedreich's ataxia than its normal counterpart."}
{"id": "PMID:206333", "title": "Possible mechanisms of normal amylase activity in hyperlipemic pancreatitis.", "content": "Lipemic serum from three patients with acute pancreatitis and type IV hyperlipemia was fractionated into very-low-density lipoproteins and clear serum. Amylase activity (determined by the Phadebas method) in the component fractions did not exceed that in the original lipemic serum. Addition of these fractions or VLDL and chylomicrons from asymptomatic patients with hyperlipemia to nonlipemic serum from patients with \"routine acute pancreatitis\" did not inhibit amylase activity or alter the electrophoretic mobility of amylase isoenzymes. Therefore the normal amylase activity often observed in hyperlipemic pancreatitis does not result from an inhibition of amylase activity by serum lipoproteins.", "contents": "Possible mechanisms of normal amylase activity in hyperlipemic pancreatitis. Lipemic serum from three patients with acute pancreatitis and type IV hyperlipemia was fractionated into very-low-density lipoproteins and clear serum. Amylase activity (determined by the Phadebas method) in the component fractions did not exceed that in the original lipemic serum. Addition of these fractions or VLDL and chylomicrons from asymptomatic patients with hyperlipemia to nonlipemic serum from patients with \"routine acute pancreatitis\" did not inhibit amylase activity or alter the electrophoretic mobility of amylase isoenzymes. Therefore the normal amylase activity often observed in hyperlipemic pancreatitis does not result from an inhibition of amylase activity by serum lipoproteins."}
{"id": "PMID:206337", "title": "CCNU-adriamycin therapy in bronchogenic carcinoma.", "content": "Forty-eight patients with advanced bronchogenic carcinoma were treated with a combination of CCNU and Adriamycin. There was an overall objective response rate of 38%. This consisted of 1 of 12 (8%) patients with epidermoid carcinoma, 5 of 15 (33%) with adenocarcinoma, 2 of 5 (40%) with large cell undifferentiated carcinoma and 10 of 16 (63%) with small cell undifferentiated carcinoma. The overall median survival time (MST) from initiation of therapy was 28 weeks. The MST was 18 weeks for patients with epidermoid carcinoma, 30 weeks for those with adenocarcinoma, 39 weeks for those with large cell carcinoma, and 30+ weeks for those with small cell carcinoma. Objective tumor response was associated with prolonged survival. There were no drug related deaths and toxicity was minimal.", "contents": "CCNU-adriamycin therapy in bronchogenic carcinoma. Forty-eight patients with advanced bronchogenic carcinoma were treated with a combination of CCNU and Adriamycin. There was an overall objective response rate of 38%. This consisted of 1 of 12 (8%) patients with epidermoid carcinoma, 5 of 15 (33%) with adenocarcinoma, 2 of 5 (40%) with large cell undifferentiated carcinoma and 10 of 16 (63%) with small cell undifferentiated carcinoma. The overall median survival time (MST) from initiation of therapy was 28 weeks. The MST was 18 weeks for patients with epidermoid carcinoma, 30 weeks for those with adenocarcinoma, 39 weeks for those with large cell carcinoma, and 30+ weeks for those with small cell carcinoma. Objective tumor response was associated with prolonged survival. There were no drug related deaths and toxicity was minimal."}
{"id": "PMID:206338", "title": "Chemotherapy of small cell carcinoma of the lung with V.P. 16-213.", "content": "A Phase II study of V.P. 16-213 administered to 47 patients suffering from small cell carcinoma of the bronchus. V.P. 16-213 was given as an intravenous infusion over 15 minutes daily for five consecutive days using 60 mg/m2/d at 14-day intervals. Oral V.P. in 100 mg doses was given twice a week between the intravenous courses. Objective response rate for this drug compared favourably with that of other single agents reported. All but two patients showed a degree of response to treatment and 24 of 47 patients showed a true objective response to treatment. The overall median survival of these patients was 225 days and localized disease 278 days. The quality of survival was such that responders lived relatively normal lives up to the latter stages of their disease. The majority of patients had a marked response in performance status, 37 out of 47  showing an improvement. Three patients are alive and well at more than 27 months. In all cases the side effects were minimal. Alopecia was common and reversible haematological complications occurred. Severe toxicity was not encountered and the drug was well tolerated with supportive antiemetic therapy at onset of treatment.", "contents": "Chemotherapy of small cell carcinoma of the lung with V.P. 16-213. A Phase II study of V.P. 16-213 administered to 47 patients suffering from small cell carcinoma of the bronchus. V.P. 16-213 was given as an intravenous infusion over 15 minutes daily for five consecutive days using 60 mg/m2/d at 14-day intervals. Oral V.P. in 100 mg doses was given twice a week between the intravenous courses. Objective response rate for this drug compared favourably with that of other single agents reported. All but two patients showed a degree of response to treatment and 24 of 47 patients showed a true objective response to treatment. The overall median survival of these patients was 225 days and localized disease 278 days. The quality of survival was such that responders lived relatively normal lives up to the latter stages of their disease. The majority of patients had a marked response in performance status, 37 out of 47  showing an improvement. Three patients are alive and well at more than 27 months. In all cases the side effects were minimal. Alopecia was common and reversible haematological complications occurred. Severe toxicity was not encountered and the drug was well tolerated with supportive antiemetic therapy at onset of treatment."}
{"id": "PMID:206339", "title": "Ifosfamide in the treatment of recurrent or disseminated lung cancer: a phase II study of two dose schedules.", "content": "Ifosfamide was administered to 21 patients with recurrent or disseminated lung cancer at a dose of 4.0 gm/M2 iv every 3 weeks. The response rate was 33% with an additional 14% showing no response or stable disease. At a dose of 1.2 gm/M2 daily for 5 days every 4 weeks, 57% of 14 patients responded with 35% showing no response or stable disease. The majority of the patients (28) had epidermoid carcinoma. Two (7%) had complete response with 9 (32%) showing partial responses. Other responses included 1/2 oat cell carcinomas and 3/6 large cell undifferentiated carcinomas. Toxicity was equal in both regimens for nausea, vomiting, increased serum LDH and neutropenia but the 5 day program had significantly less hemorrhagic cystitis. Survival was greatly influenced by response. There was no statistical difference in overall length of response between responders and the non responding/stable disease patients. But these two groups had a very significant survival advantage when compared to those patients with increasing disease. Similarly, there was a significant improvement in response duration for the low dosage regimen. Therefore, the low dose 5 day regimen is recommended because of its response rate, it has less hemorrhagic cystitis and it has better patient acceptance in that it can be given as an outpatient and does not require a Foley catheter.", "contents": "Ifosfamide in the treatment of recurrent or disseminated lung cancer: a phase II study of two dose schedules. Ifosfamide was administered to 21 patients with recurrent or disseminated lung cancer at a dose of 4.0 gm/M2 iv every 3 weeks. The response rate was 33% with an additional 14% showing no response or stable disease. At a dose of 1.2 gm/M2 daily for 5 days every 4 weeks, 57% of 14 patients responded with 35% showing no response or stable disease. The majority of the patients (28) had epidermoid carcinoma. Two (7%) had complete response with 9 (32%) showing partial responses. Other responses included 1/2 oat cell carcinomas and 3/6 large cell undifferentiated carcinomas. Toxicity was equal in both regimens for nausea, vomiting, increased serum LDH and neutropenia but the 5 day program had significantly less hemorrhagic cystitis. Survival was greatly influenced by response. There was no statistical difference in overall length of response between responders and the non responding/stable disease patients. But these two groups had a very significant survival advantage when compared to those patients with increasing disease. Similarly, there was a significant improvement in response duration for the low dosage regimen. Therefore, the low dose 5 day regimen is recommended because of its response rate, it has less hemorrhagic cystitis and it has better patient acceptance in that it can be given as an outpatient and does not require a Foley catheter."}
{"id": "PMID:206340", "title": "Amyloid stroma in a tubular carcinoma of palatal salivary gland: a histochemical and ultrastructural study.", "content": "Amyloid as defined by positive Congo red green birefringence and STB red birefringence was observed in the stroma of a tubular carcinoma of minor salivary gland origin. The amyloid exhibited additional histochemical characteristics of immunamyloid, viz., positive DMAB-nitrate and DC-reactions and spontaneous autofluorescence. Electron microscopic studies of the epithelial tumor cells displayed large amounts of cytoplasmic microfilaments similar to those present in the extracellular amyloid masses. It is suggested that the amyloid is derived from spontaneous assembly or polymerization of cytoplasmic microfibrils of the dying tumor cells as has been proposed for the amyloid associated with the calcifying epithelial odontogenic tumor (CEOT).", "contents": "Amyloid stroma in a tubular carcinoma of palatal salivary gland: a histochemical and ultrastructural study. Amyloid as defined by positive Congo red green birefringence and STB red birefringence was observed in the stroma of a tubular carcinoma of minor salivary gland origin. The amyloid exhibited additional histochemical characteristics of immunamyloid, viz., positive DMAB-nitrate and DC-reactions and spontaneous autofluorescence. Electron microscopic studies of the epithelial tumor cells displayed large amounts of cytoplasmic microfilaments similar to those present in the extracellular amyloid masses. It is suggested that the amyloid is derived from spontaneous assembly or polymerization of cytoplasmic microfibrils of the dying tumor cells as has been proposed for the amyloid associated with the calcifying epithelial odontogenic tumor (CEOT)."}
{"id": "PMID:206341", "title": "Application of a microchemical technique to the elucidation of enzyme activity profiles within single human mammary tumors.", "content": "An ultramicrochemical technique has been adapted to the evolution of enzyme profiles within individual human mammary tumors. Tandem observation of adjacent stained and lyophilized sections permitted dissection of microgram quantities of freeze-dried material within confirmed regions of malignancy. Enzymes frequently monitored to examine glycolytic, respiratory, and metastatic capacity were microanalyzed successfully: lactic dehydrogenase (LDH), phosphoglucose isomerase (PGI), malate dehydrogenase (MDH), acid phosphatase (AP), aldolase (ALD), glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK), alpha-glycerophosphate dehydrogenase (alpha-GOPDH), hexokinase (HK), and phosphofructokinase (PRK). All enzyme activities were higher in infiltrating ductal carcinomas than in fibroadenomas. Extracts of tumor cells mixed in varying proportions with brain or muscle extracts of rat evidenced no modification of expected activity. The technical adaptation described provided a sensitive methodology to resolve problems of relication, profile analysis, sample quantity, and selectivity within heterogeneous tissues.", "contents": "Application of a microchemical technique to the elucidation of enzyme activity profiles within single human mammary tumors. An ultramicrochemical technique has been adapted to the evolution of enzyme profiles within individual human mammary tumors. Tandem observation of adjacent stained and lyophilized sections permitted dissection of microgram quantities of freeze-dried material within confirmed regions of malignancy. Enzymes frequently monitored to examine glycolytic, respiratory, and metastatic capacity were microanalyzed successfully: lactic dehydrogenase (LDH), phosphoglucose isomerase (PGI), malate dehydrogenase (MDH), acid phosphatase (AP), aldolase (ALD), glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK), alpha-glycerophosphate dehydrogenase (alpha-GOPDH), hexokinase (HK), and phosphofructokinase (PRK). All enzyme activities were higher in infiltrating ductal carcinomas than in fibroadenomas. Extracts of tumor cells mixed in varying proportions with brain or muscle extracts of rat evidenced no modification of expected activity. The technical adaptation described provided a sensitive methodology to resolve problems of relication, profile analysis, sample quantity, and selectivity within heterogeneous tissues."}
{"id": "PMID:206342", "title": "Plasma cell granuloma (inflammatory pseudotumor) of the spinal cord meninges: report of a case.", "content": "A case of plasma cell granuloma (inflammatory pseudotumor) arising in the meninges of cervical spinal cord of a 37-year-old Japanese man is presented. The diagnosis was made by analogy with the similar lesions known in the lung. Its histology was characterized by infiltration of three kinds of cells; histiocytes with slight epithelioid appearance, plasma cells with numerous Russell bodies, and lymphocytes. Electron microscopy of the formalin-fixed tissue was useful for the identification of these cells, particularly of histiocytes. Although extrapulmonary plasma cell granulomas have been reported, this is the first case, to our knowledge, of this type \"tumor\" in the spinal cord meninges. Differential diagnoses have been briefly discussed.", "contents": "Plasma cell granuloma (inflammatory pseudotumor) of the spinal cord meninges: report of a case. A case of plasma cell granuloma (inflammatory pseudotumor) arising in the meninges of cervical spinal cord of a 37-year-old Japanese man is presented. The diagnosis was made by analogy with the similar lesions known in the lung. Its histology was characterized by infiltration of three kinds of cells; histiocytes with slight epithelioid appearance, plasma cells with numerous Russell bodies, and lymphocytes. Electron microscopy of the formalin-fixed tissue was useful for the identification of these cells, particularly of histiocytes. Although extrapulmonary plasma cell granulomas have been reported, this is the first case, to our knowledge, of this type \"tumor\" in the spinal cord meninges. Differential diagnoses have been briefly discussed."}
{"id": "PMID:206343", "title": "Histopathology and prognosis of Wilms tumors: results from the First National Wilms' Tumor Study.", "content": "Detailed histological analysis of 427 cases entered on the first National Wilms' Tumor Study revealed that lesions with foci of marked cytological atypism (anaplasia), and those composed predominantly of sarcomatous stroma, were associated with unfavorable outcome. Twenty-five patients had anaplasia, and 24 had sarcomatous lesions of which a total of 28 (57.1%) died of tumor. Three hundred and seventy-eight patients had tumors which showed neither of these features, and only 26 (6.9%) died of tumor. Seven of ten deaths due to tumor in patients diagnosed before two years of age were associated with sarcomatous lesions. Three sarcomatous patterns were recognized, of which one, designated \"clear cell\" sarcoma, had a predilection for bony metastases. Using criteria defined and illustrated in this paper it is possible to identify in advance those patients likely to do poorly using current therapeutic approaches.", "contents": "Histopathology and prognosis of Wilms tumors: results from the First National Wilms' Tumor Study. Detailed histological analysis of 427 cases entered on the first National Wilms' Tumor Study revealed that lesions with foci of marked cytological atypism (anaplasia), and those composed predominantly of sarcomatous stroma, were associated with unfavorable outcome. Twenty-five patients had anaplasia, and 24 had sarcomatous lesions of which a total of 28 (57.1%) died of tumor. Three hundred and seventy-eight patients had tumors which showed neither of these features, and only 26 (6.9%) died of tumor. Seven of ten deaths due to tumor in patients diagnosed before two years of age were associated with sarcomatous lesions. Three sarcomatous patterns were recognized, of which one, designated \"clear cell\" sarcoma, had a predilection for bony metastases. Using criteria defined and illustrated in this paper it is possible to identify in advance those patients likely to do poorly using current therapeutic approaches."}
{"id": "PMID:206344", "title": "Cystosarcoma phyllodes: a clinicopathologic analysis of 42 cases.", "content": "A retrospective clinicopathologic evaluation of 42 patients with cystosarcoma phyllodes was undertaken to determine if tumor size, contour, degree of stromal atypia and mitotic activity were reliable indicators of clinical behavior. Excluding size, the latter three determinants showed a positive correlation with prognosis and served as the basis of a classification in which 18 benign, 5 borderline and 19 malignant cystosarcomas were diagnosed. The tumors occurred in women averaging 44.3 years of age who most often presented with a palpable occasionally painful mass with a median diameter of 5 cm. Excision or simple mastectomy were the more frequent forms of therapy. Local recurrences were experienced by 6 patients and occurred in all 3 categories of tumor. Only malignant neoplasms developed systemic metastases which was observed in 4 patients 3 of which have died. On borderline tumor recurred 14 times and eventually proved fatal as a result of contiguous pulmonary involvement. A plea is made to label the stroma of malignant cystosarcomas as to the cell(s) of origin so future investigators may evaluate the effect of various soft tissue patterns on prognosis.", "contents": "Cystosarcoma phyllodes: a clinicopathologic analysis of 42 cases. A retrospective clinicopathologic evaluation of 42 patients with cystosarcoma phyllodes was undertaken to determine if tumor size, contour, degree of stromal atypia and mitotic activity were reliable indicators of clinical behavior. Excluding size, the latter three determinants showed a positive correlation with prognosis and served as the basis of a classification in which 18 benign, 5 borderline and 19 malignant cystosarcomas were diagnosed. The tumors occurred in women averaging 44.3 years of age who most often presented with a palpable occasionally painful mass with a median diameter of 5 cm. Excision or simple mastectomy were the more frequent forms of therapy. Local recurrences were experienced by 6 patients and occurred in all 3 categories of tumor. Only malignant neoplasms developed systemic metastases which was observed in 4 patients 3 of which have died. On borderline tumor recurred 14 times and eventually proved fatal as a result of contiguous pulmonary involvement. A plea is made to label the stroma of malignant cystosarcomas as to the cell(s) of origin so future investigators may evaluate the effect of various soft tissue patterns on prognosis."}
{"id": "PMID:206345", "title": "Peritoneoscopy in the staging of 190 patients with small-cell anaplastic carcinoma of the lung with special reference to subtyping.", "content": "Peritoneoscopy with liver biopsy was routinely done as a pretreatment staging procedure in 190 patients with small-cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 28.3% with fusiform cell type (WHO II,1), 28.9% with polygonal cell type (WHO II,2), 41.5% with lymphocytelike cell type (WHO II,3) and 1.3% with mixed types (WHO II, 4). Liver metastases were found in 21% of the patients with adequate liver biopsy. In addition macroscopic signs of liver metastases were observed in 9%. No significant differences were observed among the histological subtypes. Liver function tests, such as alkaline phosphatase, LDH and GOT, were of little value in excluding liver metastases. On the other hand, 2 of 3 abnormal liver function tests were highly indicative of liver metastases. In patients with positive liver biopsy, 41% had liver metastases alone and 76% had no other evidence of distant metastatic disease if bone-marrow involvement identified with bone marrow examination is excluded as a staging procedure.", "contents": "Peritoneoscopy in the staging of 190 patients with small-cell anaplastic carcinoma of the lung with special reference to subtyping. Peritoneoscopy with liver biopsy was routinely done as a pretreatment staging procedure in 190 patients with small-cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 28.3% with fusiform cell type (WHO II,1), 28.9% with polygonal cell type (WHO II,2), 41.5% with lymphocytelike cell type (WHO II,3) and 1.3% with mixed types (WHO II, 4). Liver metastases were found in 21% of the patients with adequate liver biopsy. In addition macroscopic signs of liver metastases were observed in 9%. No significant differences were observed among the histological subtypes. Liver function tests, such as alkaline phosphatase, LDH and GOT, were of little value in excluding liver metastases. On the other hand, 2 of 3 abnormal liver function tests were highly indicative of liver metastases. In patients with positive liver biopsy, 41% had liver metastases alone and 76% had no other evidence of distant metastatic disease if bone-marrow involvement identified with bone marrow examination is excluded as a staging procedure."}
{"id": "PMID:206346", "title": "The differences between the primary structures of mitochondrial DNAs from rat liver and ascites hepatoma (AH-130).", "content": "Rat mitochondrial DNAs (mtDNAs) of ascites hepatoma (AH-130) and normal liver cells (Donryu strain) were digested by various restriction endonucleases and the cleavage patterns compared by agarose gel electrophoresis. Different cleavage patterns were observed between AH-130 and liver mtDNAs when they were digested by HindII and EcoRI. The mtDNA of AH-130 lost one clevage site of HindII and one clevage site of EcoRI. The cleavage patterns of mtDNAs from other organs and strains tested were the same as that of liver mtDNA. From these observations we concluded that the molecular clone of AH-130 mtDNA was different from that of other mtDNAs.", "contents": "The differences between the primary structures of mitochondrial DNAs from rat liver and ascites hepatoma (AH-130). Rat mitochondrial DNAs (mtDNAs) of ascites hepatoma (AH-130) and normal liver cells (Donryu strain) were digested by various restriction endonucleases and the cleavage patterns compared by agarose gel electrophoresis. Different cleavage patterns were observed between AH-130 and liver mtDNAs when they were digested by HindII and EcoRI. The mtDNA of AH-130 lost one clevage site of HindII and one clevage site of EcoRI. The cleavage patterns of mtDNAs from other organs and strains tested were the same as that of liver mtDNA. From these observations we concluded that the molecular clone of AH-130 mtDNA was different from that of other mtDNAs."}
{"id": "PMID:206347", "title": "EBV-related cytotoxicity of Fc receptor negative T lymphocytes separated from the blood of infectious mononucleosis patients.", "content": "Epstein-Barr virus (EBV) related specific killing was demonstrated previously in the T cell enriched subpopulations of blood lymphocytes of IM patients. In the present work we demonstrate that the cytotoxic cells belong to the Fc negative T subset. T cells in the blood of IM patients can be divided in 2 categories, 1 Fc positive with non discriminative cytotoxicity and the other, Fc negative with selective cytotoxicity against EBV genome carrying lymphoblastoid cell lines.", "contents": "EBV-related cytotoxicity of Fc receptor negative T lymphocytes separated from the blood of infectious mononucleosis patients. Epstein-Barr virus (EBV) related specific killing was demonstrated previously in the T cell enriched subpopulations of blood lymphocytes of IM patients. In the present work we demonstrate that the cytotoxic cells belong to the Fc negative T subset. T cells in the blood of IM patients can be divided in 2 categories, 1 Fc positive with non discriminative cytotoxicity and the other, Fc negative with selective cytotoxicity against EBV genome carrying lymphoblastoid cell lines."}
{"id": "PMID:206348", "title": "Search for disease-related cytotoxicity in mammary tumor patients.", "content": "Blood lymphocytes from benign and malignant mammary tumor patients ahd healthy blood donors were tested for cytotoxicity against monolayer cell lines, including two which were derived from breast carcinomas. Generally, the T subset was not cytotoxic, and if so this was not restricted to the relevant cell lines. In accordance with previous results 'null' cells were most efficient in the seemingly non-selective cytotoxicity.", "contents": "Search for disease-related cytotoxicity in mammary tumor patients. Blood lymphocytes from benign and malignant mammary tumor patients ahd healthy blood donors were tested for cytotoxicity against monolayer cell lines, including two which were derived from breast carcinomas. Generally, the T subset was not cytotoxic, and if so this was not restricted to the relevant cell lines. In accordance with previous results 'null' cells were most efficient in the seemingly non-selective cytotoxicity."}
{"id": "PMID:206349", "title": "Detection of the EBV-determined nuclear antigen (EBNA) in Burkitt's lymphoma and nasopharyngeal carcinoma biopsies by the acid fixed nuclear binding (AFNB) technique.", "content": "Epstein-Barr virus (EBV) carrying biopsies of Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC) were used to examine the question whether the EBV-associated nuclear antigen (EBNA) can be demonstrated by the acid fixed nuclear binding (AFNB) technique, developed previously for the demonstration of EBNA in cultured cell lines [11]. Extracts of 5 BL and 5 NPC biopsies gave a brilliant, EBNA specific fluorescence after binding to acid fixed chicken red cells. Similar extracts of 3 other African tumors that are not known to carry the EBV-genome were negative, in spite of the fact that they were derived from EBV-seropositive patients with relatively high anti-EBV (VCA) antibody titers. Crude extraction and DNA-cellulose purification gave equally active extracts, provided that incubation was carried out at 4 degrees C. These results show that the acid fixed nuclear binding technique can be applied to biopsy material. This may be helpful in searching for EBNA carrying cells in heterogeneous normal and tumor tissues in vivo where the direct in situ ACIF staining for EBNA is known to meet great difficulties.", "contents": "Detection of the EBV-determined nuclear antigen (EBNA) in Burkitt's lymphoma and nasopharyngeal carcinoma biopsies by the acid fixed nuclear binding (AFNB) technique. Epstein-Barr virus (EBV) carrying biopsies of Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC) were used to examine the question whether the EBV-associated nuclear antigen (EBNA) can be demonstrated by the acid fixed nuclear binding (AFNB) technique, developed previously for the demonstration of EBNA in cultured cell lines [11]. Extracts of 5 BL and 5 NPC biopsies gave a brilliant, EBNA specific fluorescence after binding to acid fixed chicken red cells. Similar extracts of 3 other African tumors that are not known to carry the EBV-genome were negative, in spite of the fact that they were derived from EBV-seropositive patients with relatively high anti-EBV (VCA) antibody titers. Crude extraction and DNA-cellulose purification gave equally active extracts, provided that incubation was carried out at 4 degrees C. These results show that the acid fixed nuclear binding technique can be applied to biopsy material. This may be helpful in searching for EBNA carrying cells in heterogeneous normal and tumor tissues in vivo where the direct in situ ACIF staining for EBNA is known to meet great difficulties."}
{"id": "PMID:206351", "title": "Immunoreactive beta-endorphin in the rat mammotropic transplantable tumor (MtT-F4).", "content": "Raised levels of what appeared to be beta-lipotropin (beta-LPH), beta-melanotropic hormone, and beta-endorphin were detected by radioimmunoassay in the plasma of rats bearing the mammotropic transplantable pituitary tumor MtT-F4. The immunoreactivity to anti-beta-endorphin in the assay was displayed by a substance with the molecular weight of beta-LPH, as determined by gel filtration. Isolated cells of MtT-F4 tumor incubated in vitro released immunoreactive beta-LPH and beta-endorphin, with the expected molecular weights, into the incubation medium. These results suggest that the pituitary transplantable rat tumor MtT-F4 secretes peptides structurally related to beta-LPH.", "contents": "Immunoreactive beta-endorphin in the rat mammotropic transplantable tumor (MtT-F4). Raised levels of what appeared to be beta-lipotropin (beta-LPH), beta-melanotropic hormone, and beta-endorphin were detected by radioimmunoassay in the plasma of rats bearing the mammotropic transplantable pituitary tumor MtT-F4. The immunoreactivity to anti-beta-endorphin in the assay was displayed by a substance with the molecular weight of beta-LPH, as determined by gel filtration. Isolated cells of MtT-F4 tumor incubated in vitro released immunoreactive beta-LPH and beta-endorphin, with the expected molecular weights, into the incubation medium. These results suggest that the pituitary transplantable rat tumor MtT-F4 secretes peptides structurally related to beta-LPH."}
{"id": "PMID:206352", "title": "Differences in total mitochondrial proteins and proteins synthesized by mitochondria from rat liver and Morris hepatomas 9618A, 5123C, and 5123tc.", "content": "Mitochondria were isolated from a slow-growing (9618A) and two intermediate-to-fast-growing (5123C, 5123tc) Morris hepatomas and host livers. The mitochondrial proteins were solubilized and fractionated on sodium dodecyl sulfate:polyacrylamide slab gels. One Coomassie blue-stained band was absent or reduced in amount in all tumors relative to host livers. In addition, a major mitochondrial enzyme present in normal liver, carbamyl phosphate synthetase, was missing or greatly reduced in the slow-growing, highly differentiated hepatoma 9618A, a tumor that is considered to be similar to normal liver in many biochemical and morphological respects. Incubation of mitochondria with [35S]methionine and a suitable amino acid incorporation system resulted in labeling of specific mitochondrial proteins. Autoradiography of the slab gels disclosed four prominently labeled fractions and a number of minor fractions. Preparations from hepatoma 5123tc demonstrated two labeled bands that were absent or greatly reduced in host liver. Host liver preparations displayed a minor band that was absent or greatly reduced in hepatoma 5123C. However, no single change in labeling pattern was common to all three tumors, suggesting the absence of a causal relationship between carcinogenesis and mutations in mitochondrial DNA.", "contents": "Differences in total mitochondrial proteins and proteins synthesized by mitochondria from rat liver and Morris hepatomas 9618A, 5123C, and 5123tc. Mitochondria were isolated from a slow-growing (9618A) and two intermediate-to-fast-growing (5123C, 5123tc) Morris hepatomas and host livers. The mitochondrial proteins were solubilized and fractionated on sodium dodecyl sulfate:polyacrylamide slab gels. One Coomassie blue-stained band was absent or reduced in amount in all tumors relative to host livers. In addition, a major mitochondrial enzyme present in normal liver, carbamyl phosphate synthetase, was missing or greatly reduced in the slow-growing, highly differentiated hepatoma 9618A, a tumor that is considered to be similar to normal liver in many biochemical and morphological respects. Incubation of mitochondria with [35S]methionine and a suitable amino acid incorporation system resulted in labeling of specific mitochondrial proteins. Autoradiography of the slab gels disclosed four prominently labeled fractions and a number of minor fractions. Preparations from hepatoma 5123tc demonstrated two labeled bands that were absent or greatly reduced in host liver. Host liver preparations displayed a minor band that was absent or greatly reduced in hepatoma 5123C. However, no single change in labeling pattern was common to all three tumors, suggesting the absence of a causal relationship between carcinogenesis and mutations in mitochondrial DNA."}
{"id": "PMID:206353", "title": "Alkyl methane sulfonate mutation of diploid human lymphoblasts and Salmonella typhimurium.", "content": "Concentration dependence of mutation in equigenerational exposures to methyl, ethyl, propyl, and butyl methanesulfonates has been determined in diploid human lymphoblasts and Salmonella typhimurium. Forward mutation was measured at the hypoxanthine guanine phosphoribosyltransferase locus in human lymphoblasts and at the putative guanine phosphoribosyltransferase locus in S. typhimurium. Reverse mutation at the his G46 locus was also measured in S. typhimurium. This analysis and previous reports support the conclusion that S. typhimurium and mammalian cells are essentially equisensitive to the mutagenic effects of ethyl methanesulfonate when concentration and exposure time are taken into account. Comparison of forward and reverse mutation assays in S. typhimurium reveals no important differences in sensitivities for the four compounds studied.", "contents": "Alkyl methane sulfonate mutation of diploid human lymphoblasts and Salmonella typhimurium. Concentration dependence of mutation in equigenerational exposures to methyl, ethyl, propyl, and butyl methanesulfonates has been determined in diploid human lymphoblasts and Salmonella typhimurium. Forward mutation was measured at the hypoxanthine guanine phosphoribosyltransferase locus in human lymphoblasts and at the putative guanine phosphoribosyltransferase locus in S. typhimurium. Reverse mutation at the his G46 locus was also measured in S. typhimurium. This analysis and previous reports support the conclusion that S. typhimurium and mammalian cells are essentially equisensitive to the mutagenic effects of ethyl methanesulfonate when concentration and exposure time are taken into account. Comparison of forward and reverse mutation assays in S. typhimurium reveals no important differences in sensitivities for the four compounds studied."}
{"id": "PMID:206354", "title": "Turnover of messenger RNA in transplantable hepatomas and host liver of rats.", "content": "The turnover of messenger RNA (mRNA) in two intrahepatically transplantable hepatoma (5123 and 19) and host livers of Buffalo rats was evaluated with four different approaches. [14C]Orotic acid incorporation into the rapidly labeled peak between 18S and 4S of total polyribosomal RNA was measured. In vitro RNase assay of [14C]orotic acid-labeled mRNA of polyribosomes was utilized. The decay of mRNA as reflected by disaggregation of free and membrane-bound polyribosomes at intervals after actinomycin D treatment was determined. The incorporation of [14C]orotic acid into polyadenylic acid-mRNA of free and membrane-bound polyribosomes was assayed. The results revealed that the turnover of mRNA of total, free, and membrane-bound polyribosomes was greater in the host livers than it was in the two hepatomas. In host livers the turnover of mRNA of the free polyribosomes was greater than that of the membrane-bound polyribosomes. In the two hepatomas the turnover of mRNA of free polyribosomes was at a similar rate as that of membrane bound polyribosomes. Hepatoma 19, which grow more rapidly and is less differentiated morphologically than is hepatoma 5123, appeared to have a slower turnover of mRNA than did hepatoma 5123. Measurement of RNase activity revealed greater activity in host livers than in hepatomas.", "contents": "Turnover of messenger RNA in transplantable hepatomas and host liver of rats. The turnover of messenger RNA (mRNA) in two intrahepatically transplantable hepatoma (5123 and 19) and host livers of Buffalo rats was evaluated with four different approaches. [14C]Orotic acid incorporation into the rapidly labeled peak between 18S and 4S of total polyribosomal RNA was measured. In vitro RNase assay of [14C]orotic acid-labeled mRNA of polyribosomes was utilized. The decay of mRNA as reflected by disaggregation of free and membrane-bound polyribosomes at intervals after actinomycin D treatment was determined. The incorporation of [14C]orotic acid into polyadenylic acid-mRNA of free and membrane-bound polyribosomes was assayed. The results revealed that the turnover of mRNA of total, free, and membrane-bound polyribosomes was greater in the host livers than it was in the two hepatomas. In host livers the turnover of mRNA of the free polyribosomes was greater than that of the membrane-bound polyribosomes. In the two hepatomas the turnover of mRNA of free polyribosomes was at a similar rate as that of membrane bound polyribosomes. Hepatoma 19, which grow more rapidly and is less differentiated morphologically than is hepatoma 5123, appeared to have a slower turnover of mRNA than did hepatoma 5123. Measurement of RNase activity revealed greater activity in host livers than in hepatomas."}
{"id": "PMID:206356", "title": "Induction of peripheral neuroblastomas in Syrian hamsters after injection as neonates with JC virus, a human polyoma virus.", "content": "Neuroblastomas developed in 10 of 31 Syrian hamsters inoculated intraocularly with JC virus, a human polyoma virus. The latent period was 6 to 11 months. Primary tumors occurred in the abdominal cavity, pelvis, mediastinum, and neck region. The origin of one tumor from the adrenal gland was demonstrated. Metastases were seen in the liver, bone marrow, and lymph nodes. Two neuroblastomas arising in this experiment were transplanted serially in weanling hamsters, and a tissue culture cell line was established from one of the transplanted tumors. T-antigen was detected in three of five primary tumors tested and in the transplanted tumors. Antibody against T-antigen was demonstrated in sera from five of six animals with neuroblastomas. Neuroblastomas also developed after combined s.c. and i.p. injection of JC virus.", "contents": "Induction of peripheral neuroblastomas in Syrian hamsters after injection as neonates with JC virus, a human polyoma virus. Neuroblastomas developed in 10 of 31 Syrian hamsters inoculated intraocularly with JC virus, a human polyoma virus. The latent period was 6 to 11 months. Primary tumors occurred in the abdominal cavity, pelvis, mediastinum, and neck region. The origin of one tumor from the adrenal gland was demonstrated. Metastases were seen in the liver, bone marrow, and lymph nodes. Two neuroblastomas arising in this experiment were transplanted serially in weanling hamsters, and a tissue culture cell line was established from one of the transplanted tumors. T-antigen was detected in three of five primary tumors tested and in the transplanted tumors. Antibody against T-antigen was demonstrated in sera from five of six animals with neuroblastomas. Neuroblastomas also developed after combined s.c. and i.p. injection of JC virus."}
{"id": "PMID:206358", "title": "Radioimmunoassay for protein p28 of murine mammary tumor virus in organs and serum of mice and search for related antigens in human sera and breast cancer extracts.", "content": "The main protein of the core of murine mammary tumor virus, with a molecular weight of 28,000 (p28), was solubilized by deoxycholate treatment of the virus and purified by Ultrogel ACA-54 filtration and hydroxyapatite chromatography. This protein was used as labeled antigen in a highly specific and reproducible radioimmunoassay. Organ extracts of uninfected C57BL mice did not contain p28, but organ extracts of infected RIII mice did contain the antigen. Despite the high content in the mammary gland, the level of p28 in the other organs was identical in male and female mice. Sera of uninfected mice and the majority of the sera of infected mice did not contain the antigen. The investigation included 338 human sera (50, normal; 157, breast cancer; 77, polycystic disease; 32, benign mastopathy; 12, fibroadenoma; 10, at risk of developing breast cancer). None contained an antigen related to p28. Eight of 24 extracts of human breast cancer gave results that appeared weakly positive, possibly as a result of proteolysis. Extracts of healthy breast tissue and the serum from the breast arterial and venous blood of corresponding patients were negative.", "contents": "Radioimmunoassay for protein p28 of murine mammary tumor virus in organs and serum of mice and search for related antigens in human sera and breast cancer extracts. The main protein of the core of murine mammary tumor virus, with a molecular weight of 28,000 (p28), was solubilized by deoxycholate treatment of the virus and purified by Ultrogel ACA-54 filtration and hydroxyapatite chromatography. This protein was used as labeled antigen in a highly specific and reproducible radioimmunoassay. Organ extracts of uninfected C57BL mice did not contain p28, but organ extracts of infected RIII mice did contain the antigen. Despite the high content in the mammary gland, the level of p28 in the other organs was identical in male and female mice. Sera of uninfected mice and the majority of the sera of infected mice did not contain the antigen. The investigation included 338 human sera (50, normal; 157, breast cancer; 77, polycystic disease; 32, benign mastopathy; 12, fibroadenoma; 10, at risk of developing breast cancer). None contained an antigen related to p28. Eight of 24 extracts of human breast cancer gave results that appeared weakly positive, possibly as a result of proteolysis. Extracts of healthy breast tissue and the serum from the breast arterial and venous blood of corresponding patients were negative."}
{"id": "PMID:206359", "title": "Yoshi 864 (1-propanol, 3,3'-iminodi-, dimethanesulfonate [ester], hydrochloride): a phase II study in solid tumors.", "content": "Two hundred and eight acceptable patients were treated with Yoshi 864 (2 mg/kg/day by iv push X 5 days repeated once every 6 weeks). Toxicity was minimal. There was an overall response rate of 11%. Cross resistance with other alkylating agents may not be present. Because of its lack of toxicity, Yoshi 864 should be further evaluated in chronic myelocytic leukemia, lymphomas, and carcinomas of the ovary and bladder where significant responses were seen. It should also be evaluated in combinations as a replacement for other alkylating agents which cause more nausea and vomiting.", "contents": "Yoshi 864 (1-propanol, 3,3'-iminodi-, dimethanesulfonate [ester], hydrochloride): a phase II study in solid tumors. Two hundred and eight acceptable patients were treated with Yoshi 864 (2 mg/kg/day by iv push X 5 days repeated once every 6 weeks). Toxicity was minimal. There was an overall response rate of 11%. Cross resistance with other alkylating agents may not be present. Because of its lack of toxicity, Yoshi 864 should be further evaluated in chronic myelocytic leukemia, lymphomas, and carcinomas of the ovary and bladder where significant responses were seen. It should also be evaluated in combinations as a replacement for other alkylating agents which cause more nausea and vomiting."}
{"id": "PMID:206361", "title": "2-acetamido-2-deoxy-alpha-D-galactosidases of Clostridium perfringens. Separation and characterization of an exoglycosidase and an oligosaccharidase.", "content": "Two distinct 2-acetamido-2-deoxy-alpha-D-galactosidases have been separated from filtrates of cultured Clostridium perfringens by electrophoresis in 6.5% poly(acrylamide) gels. One of the enzymes had a mobility of 0.32--0.36 (relative to Bromophenol Blue) and was identified as the exoglycosidase, 2-acetamido-2-deoxy-alpha-D-galactosidase. It appears to be the same enzyme as that reported in 1972 by McGuire et al. The second of the two enzymes, having a relative mobility of 0.42--0.46, corresponds to the oligosaccharidase reported in 1972 by Huang and Aminoff. The A-specificities of human type-A erythrocytes and of water-soluble glycoproteins having A-activity are both destroyed by incubation with the 2-acetamido-2-deoxy-alpha-D-galactosidase, but not on incubation with the oligosaccharidase. A concomitant rise in blood-group O(H) activity, as indicated by the use of a lectin from Ulex europeus, occurred in the A-erythrocytes treated with the exoglycosidase 2-acetamido-2-deoxy-alpha-D-galactosidase.", "contents": "2-acetamido-2-deoxy-alpha-D-galactosidases of Clostridium perfringens. Separation and characterization of an exoglycosidase and an oligosaccharidase. Two distinct 2-acetamido-2-deoxy-alpha-D-galactosidases have been separated from filtrates of cultured Clostridium perfringens by electrophoresis in 6.5% poly(acrylamide) gels. One of the enzymes had a mobility of 0.32--0.36 (relative to Bromophenol Blue) and was identified as the exoglycosidase, 2-acetamido-2-deoxy-alpha-D-galactosidase. It appears to be the same enzyme as that reported in 1972 by McGuire et al. The second of the two enzymes, having a relative mobility of 0.42--0.46, corresponds to the oligosaccharidase reported in 1972 by Huang and Aminoff. The A-specificities of human type-A erythrocytes and of water-soluble glycoproteins having A-activity are both destroyed by incubation with the 2-acetamido-2-deoxy-alpha-D-galactosidase, but not on incubation with the oligosaccharidase. A concomitant rise in blood-group O(H) activity, as indicated by the use of a lectin from Ulex europeus, occurred in the A-erythrocytes treated with the exoglycosidase 2-acetamido-2-deoxy-alpha-D-galactosidase."}
{"id": "PMID:206362", "title": "Studies on antiviral glycosides. Synthesis and biological evaluation of various phenyl glycosides.", "content": "A variety of analogues and derivatives of phenyl glycosides were synthesized for examination of their biological activities and of the relationship between structure and antiviral activity. For antiviral activity, a 6-deoxy-6-halogeno-D-glucose residue was most suitable for the carbohydrate moiety and p-alkylphenyl groups for the aglycone moiety. Based on these results, p-(sec-butyl)phenyl 6-chloro-6-deoxy-beta-D-glucopyranoside and p-(sec-butyl)phenyl 6-deoxy-6-iodo-beta-D-glucopyranoside were prepared, and the former compound was found to be the most potent antiviral substance, in this series, against influenza and Herpes simplex virus. The anomeric configuration of phenyl glycosides did not contribute to the antiviral activity.", "contents": "Studies on antiviral glycosides. Synthesis and biological evaluation of various phenyl glycosides. A variety of analogues and derivatives of phenyl glycosides were synthesized for examination of their biological activities and of the relationship between structure and antiviral activity. For antiviral activity, a 6-deoxy-6-halogeno-D-glucose residue was most suitable for the carbohydrate moiety and p-alkylphenyl groups for the aglycone moiety. Based on these results, p-(sec-butyl)phenyl 6-chloro-6-deoxy-beta-D-glucopyranoside and p-(sec-butyl)phenyl 6-deoxy-6-iodo-beta-D-glucopyranoside were prepared, and the former compound was found to be the most potent antiviral substance, in this series, against influenza and Herpes simplex virus. The anomeric configuration of phenyl glycosides did not contribute to the antiviral activity."}
{"id": "PMID:206363", "title": "Effects of propranolol on baroreflex sensitivity in borderline hypertension.", "content": "Patients with borderline hypertension have reduced baroreflex sensitivity, but the mechanism is not known. These patients reportedly have increased beta-adrenergic activity. Since beta-adrenergic activity has been reported to antagonise baroreflex sensitivity, this study was undertaken, first to determine if propranolol increases baroreflex sensitivity in borderline hypertension, and secondly to test the hypothesis that increased beta-adrenergic activity might contribute to reduced baroreflex sensitivity in these patients. The effect of beta-adrenergic blockade on baroreflex sensitivity was studied in 11 patients with borderline hypertension and was compared with that of six age-matched control subjects. Baroreflex sensitivity was significantly increased by propranolol, 0.2 mg.kg-1 intravenously, in patients with borderline hypertension. However, after propranolol baroreflex sensitivity was still lower in the patients with borderline hypertension than it was in control subjects (P less than 0.01). The results suggest, first that increased beta-adrenergic activity is not a major factor contributing to decreased baroreflex sensitivity in borderline hypertension and, second that increased baroreflex sensitivity produced by propranolol might contribute to the anti-hypertensive effect of this drug.", "contents": "Effects of propranolol on baroreflex sensitivity in borderline hypertension. Patients with borderline hypertension have reduced baroreflex sensitivity, but the mechanism is not known. These patients reportedly have increased beta-adrenergic activity. Since beta-adrenergic activity has been reported to antagonise baroreflex sensitivity, this study was undertaken, first to determine if propranolol increases baroreflex sensitivity in borderline hypertension, and secondly to test the hypothesis that increased beta-adrenergic activity might contribute to reduced baroreflex sensitivity in these patients. The effect of beta-adrenergic blockade on baroreflex sensitivity was studied in 11 patients with borderline hypertension and was compared with that of six age-matched control subjects. Baroreflex sensitivity was significantly increased by propranolol, 0.2 mg.kg-1 intravenously, in patients with borderline hypertension. However, after propranolol baroreflex sensitivity was still lower in the patients with borderline hypertension than it was in control subjects (P less than 0.01). The results suggest, first that increased beta-adrenergic activity is not a major factor contributing to decreased baroreflex sensitivity in borderline hypertension and, second that increased baroreflex sensitivity produced by propranolol might contribute to the anti-hypertensive effect of this drug."}
{"id": "PMID:206365", "title": "Immunocytological detection and localization of a peptide reacting with an alpha-endorphin antiserum in the corticotropic and melanotropic cells of the trout pituitary (Salmo irideus Gibb).", "content": "In the pituitary of the trout, the corticotropic and melanotropic cells display a strong immunocytological reaction with alpha-endorphin antiserum. This reaction persists even when alpha-endorphin antisera treated with beta-1-24ACTH or alpha-MSH are used. In the absence of pharmacological tests on the endorphic potencies of the compounds involved in the immunoreaction, it is not yeat clear whether this reaction is due to the presence of an alpha-endorphin-like peptide or simply an immunologically related peptide without the properties of endorphin. However, the presence of such peptides in the fish pituitary is interesting from the comparative point of view.", "contents": "Immunocytological detection and localization of a peptide reacting with an alpha-endorphin antiserum in the corticotropic and melanotropic cells of the trout pituitary (Salmo irideus Gibb). In the pituitary of the trout, the corticotropic and melanotropic cells display a strong immunocytological reaction with alpha-endorphin antiserum. This reaction persists even when alpha-endorphin antisera treated with beta-1-24ACTH or alpha-MSH are used. In the absence of pharmacological tests on the endorphic potencies of the compounds involved in the immunoreaction, it is not yeat clear whether this reaction is due to the presence of an alpha-endorphin-like peptide or simply an immunologically related peptide without the properties of endorphin. However, the presence of such peptides in the fish pituitary is interesting from the comparative point of view."}
{"id": "PMID:206370", "title": "[Desensitization of adrenal tumor cells Y1 by ACTH and dibutyryl cyclic AMP].", "content": "The steroidogenic responsiveness of mouse adrenal tumor cell line (Y-1) to ACTH and db cAMP declines after stimulations by these compounds. The desensitization induced by ACTH appears early and is more pronounced than that induced by db cAMP. After removal of the hormone or the nucleotide, the recovery of cell responsiveness to both stimuli isprogressively restored. Full responsiveness is recovered within 24 hrs.", "contents": "[Desensitization of adrenal tumor cells Y1 by ACTH and dibutyryl cyclic AMP]. The steroidogenic responsiveness of mouse adrenal tumor cell line (Y-1) to ACTH and db cAMP declines after stimulations by these compounds. The desensitization induced by ACTH appears early and is more pronounced than that induced by db cAMP. After removal of the hormone or the nucleotide, the recovery of cell responsiveness to both stimuli isprogressively restored. Full responsiveness is recovered within 24 hrs."}
{"id": "PMID:206371", "title": "[Periodate oxidation of lymphocyte membrane glycoconjugates].", "content": "Mouse spleen cells free of erythrocytes were suspended in PBS at a concentration of 2 X 10(7) cells/ml and mixed with an equal volume of sodium periodate in PBS for 10 min. at 4 degrees C to give a final concentration of periodate ranging from 10(-4) M to 5 X 10(-3) M. The cells were then washed and suspended (60 X 10(6) ml) in PBS containing 3H-labelled sodium borohydrate and incubated for 30 min, at 23 degrees C. Following this, the cells were washed and the pellets treated with H2SO4 0.1 N for 60 min. at 80 degrees C. Compounds liberated by such treatment, were identified by chromatography as derivates of sialic acid. The data provide direct evidence that the mitogenic effect of sodium periodate is associated to the oxidation of the sialic acid residues on the lymphocyte membrane.", "contents": "[Periodate oxidation of lymphocyte membrane glycoconjugates]. Mouse spleen cells free of erythrocytes were suspended in PBS at a concentration of 2 X 10(7) cells/ml and mixed with an equal volume of sodium periodate in PBS for 10 min. at 4 degrees C to give a final concentration of periodate ranging from 10(-4) M to 5 X 10(-3) M. The cells were then washed and suspended (60 X 10(6) ml) in PBS containing 3H-labelled sodium borohydrate and incubated for 30 min, at 23 degrees C. Following this, the cells were washed and the pellets treated with H2SO4 0.1 N for 60 min. at 80 degrees C. Compounds liberated by such treatment, were identified by chromatography as derivates of sialic acid. The data provide direct evidence that the mitogenic effect of sodium periodate is associated to the oxidation of the sialic acid residues on the lymphocyte membrane."}
{"id": "PMID:206372", "title": "[Purification of calf thymus adenosine diphosphate ribose polymerase].", "content": "Calf thymus poly ADPR polymerase has been purified to electrophoretic homogenity. The enzyme has a molecular weight of 120,000 +/- 10,000 dalton. The substrate affinity is very high (apparent Km 82.5 micrometer). The presence of exogenous DNA does not appear to be a requisite for enzymatic activity of the purified enzyme.", "contents": "[Purification of calf thymus adenosine diphosphate ribose polymerase]. Calf thymus poly ADPR polymerase has been purified to electrophoretic homogenity. The enzyme has a molecular weight of 120,000 +/- 10,000 dalton. The substrate affinity is very high (apparent Km 82.5 micrometer). The presence of exogenous DNA does not appear to be a requisite for enzymatic activity of the purified enzyme."}
{"id": "PMID:206373", "title": "[Susceptibility to avian tumor viruses: determination of chick phenotypes].", "content": "The genetic cellular susceptibility to avian sarcoma viruses (RSV) of subgroups A, B, C and E has been determined in one week old Chicks. Fibroblasts from pin feathers were grown in vitro and tested by focus formation after infection. This technique will allow, for the first time, the study of the influence of the host phenotypes (susceptibility or resistance to the different subgroups of RSV) upon the immune response to a given virus.", "contents": "[Susceptibility to avian tumor viruses: determination of chick phenotypes]. The genetic cellular susceptibility to avian sarcoma viruses (RSV) of subgroups A, B, C and E has been determined in one week old Chicks. Fibroblasts from pin feathers were grown in vitro and tested by focus formation after infection. This technique will allow, for the first time, the study of the influence of the host phenotypes (susceptibility or resistance to the different subgroups of RSV) upon the immune response to a given virus."}
{"id": "PMID:206374", "title": "[Tumor specific surface antigen in the culture medium of a rat cell line transformed by Rous sarcoma virus].", "content": "TSSA is detected on transformed cells by a mixed hemadsorption reaction. The medium of cultures of Rat cells transformed by Rous sarcoma virus (Prague strain, sub-group C) contains a soluble factor which specifically inhibits this reaction. This factor thus possesses the antigenic activity of TSSA which is associated with the presence of a component of molecular weight 42,000 by polyacrylamide gel electrophoresis.", "contents": "[Tumor specific surface antigen in the culture medium of a rat cell line transformed by Rous sarcoma virus]. TSSA is detected on transformed cells by a mixed hemadsorption reaction. The medium of cultures of Rat cells transformed by Rous sarcoma virus (Prague strain, sub-group C) contains a soluble factor which specifically inhibits this reaction. This factor thus possesses the antigenic activity of TSSA which is associated with the presence of a component of molecular weight 42,000 by polyacrylamide gel electrophoresis."}
{"id": "PMID:206375", "title": "[Cell transformation in vitro by transfer of isolated metaphase chromosomes].", "content": "Human and murine cells can be transformed in vitro following transfer of chromosomes (transfection) isolated from tumour (HeLa) or SV40-transformed (WI98VaD) human cells. An abortive transformation of Mouse cells is observed in soft-agar medium. An instability of the transformed phenotype is exhibited by the transfected human cells, following the isolation of colonies growing in soft-agar or low-serum medium. Nevertheless, two transformed cell lines (809 ch. VaD, Cl.5P and Cl.6P) could be established in culture.", "contents": "[Cell transformation in vitro by transfer of isolated metaphase chromosomes]. Human and murine cells can be transformed in vitro following transfer of chromosomes (transfection) isolated from tumour (HeLa) or SV40-transformed (WI98VaD) human cells. An abortive transformation of Mouse cells is observed in soft-agar medium. An instability of the transformed phenotype is exhibited by the transfected human cells, following the isolation of colonies growing in soft-agar or low-serum medium. Nevertheless, two transformed cell lines (809 ch. VaD, Cl.5P and Cl.6P) could be established in culture."}
{"id": "PMID:206376", "title": "[Characterization of the partial inhibition, by deficiency in serum factors, of multiplication of SV3T3 transformed fibroblasts].", "content": "Partial inhibition, by serum starvation, of multiplication of SV3T3 transformed fibroblasts was studied by cultivating cells in a medium containing 1% of serum. Two different and successive states are described: a first step, with a rate of multiplication for 24 hrs, which is lowered (2 instead of 3 in a normal medium containing 10% of serum) but which remains constant (i.e. exponential multiplication), the observed inhibition being reversed by normal medium; a second step, where the rate of multiplication for 24 hrs, decreases very fast, and which is not reversible.", "contents": "[Characterization of the partial inhibition, by deficiency in serum factors, of multiplication of SV3T3 transformed fibroblasts]. Partial inhibition, by serum starvation, of multiplication of SV3T3 transformed fibroblasts was studied by cultivating cells in a medium containing 1% of serum. Two different and successive states are described: a first step, with a rate of multiplication for 24 hrs, which is lowered (2 instead of 3 in a normal medium containing 10% of serum) but which remains constant (i.e. exponential multiplication), the observed inhibition being reversed by normal medium; a second step, where the rate of multiplication for 24 hrs, decreases very fast, and which is not reversible."}
{"id": "PMID:206377", "title": "[Effects of hexamethylenebisacetamide on the differentiation of embryonal carcinoma cells].", "content": "HMBA induces differentiation in the whole population of some multipotential embryonic carcinoma cells. Morphological, biochemical and immunological changes can be observed even after short treatment. The cells lose the embryonal F9 antigen without acquiring H-2 antigens.", "contents": "[Effects of hexamethylenebisacetamide on the differentiation of embryonal carcinoma cells]. HMBA induces differentiation in the whole population of some multipotential embryonic carcinoma cells. Morphological, biochemical and immunological changes can be observed even after short treatment. The cells lose the embryonal F9 antigen without acquiring H-2 antigens."}
{"id": "PMID:206378", "title": "[Effect of periodate oxidation of glycoconjugates of lymphocyte membranes on the immune response in vitro].", "content": "Mouse spleen cells treated with sodium periodate for 10 min. at 4 degrees C are stimulated to undergo blastogenesis and to incorporate thymidine. The effect of such treatment on the antibody response in vitro induced by Sheep red blood cells has been evaluated. Periodate-induced proliferation is accompanied by a marked inhibition of the immune response to this antigen. At concentrations leading to mitogenesis, no cytotoxic effect of periodate was observed and treated cells survived well on tissue culture. Cell recoveries from samples treated with periodate at the optimal mitogenic dose, were markedly enhanced when harvested at different days after culturing wheras lower antibody forming cells numbers wereconsistently observed during the culture period.", "contents": "[Effect of periodate oxidation of glycoconjugates of lymphocyte membranes on the immune response in vitro]. Mouse spleen cells treated with sodium periodate for 10 min. at 4 degrees C are stimulated to undergo blastogenesis and to incorporate thymidine. The effect of such treatment on the antibody response in vitro induced by Sheep red blood cells has been evaluated. Periodate-induced proliferation is accompanied by a marked inhibition of the immune response to this antigen. At concentrations leading to mitogenesis, no cytotoxic effect of periodate was observed and treated cells survived well on tissue culture. Cell recoveries from samples treated with periodate at the optimal mitogenic dose, were markedly enhanced when harvested at different days after culturing wheras lower antibody forming cells numbers wereconsistently observed during the culture period."}
{"id": "PMID:206379", "title": "[Effects of bilateral dorsolateral pontine tegmentum lesions on hippocampus theta rhythm during paradoxical sleep in the rat].", "content": "Electrolytic lesions of the dorsolateral pontine tegmentum aimed at the locus coeruleus (LC) were performed bilaterally in 13 chronically implanted Rats. Following lesions, transient alterations of characteristic components of theta rhythm appeared. No shortening of duration of paradoxical sleep (PS) was observed. These results do not support the hypothesis that neurons of LC are directly involved in the production of theta rhythm during PS; moreover they seem not to be necessary to the normal appearance of this state of sleep.", "contents": "[Effects of bilateral dorsolateral pontine tegmentum lesions on hippocampus theta rhythm during paradoxical sleep in the rat]. Electrolytic lesions of the dorsolateral pontine tegmentum aimed at the locus coeruleus (LC) were performed bilaterally in 13 chronically implanted Rats. Following lesions, transient alterations of characteristic components of theta rhythm appeared. No shortening of duration of paradoxical sleep (PS) was observed. These results do not support the hypothesis that neurons of LC are directly involved in the production of theta rhythm during PS; moreover they seem not to be necessary to the normal appearance of this state of sleep."}
{"id": "PMID:206380", "title": "[Self-association of 5'-GMP: nucelation by potassium ions].", "content": "23Na and 39K nuclear magnetic resonance are used to follow the self-assocation of 5'-GMP in aqueous solutions. For a 0,1 M concentration in 5'-GMP, large aggregates are formed only in presence of the potassium ion, at greater than 0.2 M concentrations. They do not appear with the other alkali metal cations. A plausible explantation is inclusion of the cation in the central cavity of 5'-GMP tetramers, with a marked selectivity in favor of potassium.", "contents": "[Self-association of 5'-GMP: nucelation by potassium ions]. 23Na and 39K nuclear magnetic resonance are used to follow the self-assocation of 5'-GMP in aqueous solutions. For a 0,1 M concentration in 5'-GMP, large aggregates are formed only in presence of the potassium ion, at greater than 0.2 M concentrations. They do not appear with the other alkali metal cations. A plausible explantation is inclusion of the cation in the central cavity of 5'-GMP tetramers, with a marked selectivity in favor of potassium."}
{"id": "PMID:206381", "title": "[Receptors for vasoactic intestinal peptide (VIP) in human colonic adenocarcinoma membranes: specific binding and stimulation of adenylate cyclase].", "content": "Human colonic adenocarcinoma plasma membranes exhibit specific receptors for VIP. Adenylate cyclase activity is stimulated by a VIP concentration as low as 10(-10) mol/1.", "contents": "[Receptors for vasoactic intestinal peptide (VIP) in human colonic adenocarcinoma membranes: specific binding and stimulation of adenylate cyclase]. Human colonic adenocarcinoma plasma membranes exhibit specific receptors for VIP. Adenylate cyclase activity is stimulated by a VIP concentration as low as 10(-10) mol/1."}
{"id": "PMID:206382", "title": "[Immunofluorescent localization of beta-lipotropin (beta-LPH) and beta-endorphins in normal and anencephalic human fetal pituitary gland].", "content": "The use of antibodies to alpha-(17-39) ACTH, beta-LPH, alpha- and beta-endorphins has enabled the detection of immunoreactive cells in human fetal pituitary glands as early as the eight week of gestation. The same cells reacted with the different antibodies. Immunoreactive cells were also observed in the pituitary of 6 human anencephalic fetuses.", "contents": "[Immunofluorescent localization of beta-lipotropin (beta-LPH) and beta-endorphins in normal and anencephalic human fetal pituitary gland]. The use of antibodies to alpha-(17-39) ACTH, beta-LPH, alpha- and beta-endorphins has enabled the detection of immunoreactive cells in human fetal pituitary glands as early as the eight week of gestation. The same cells reacted with the different antibodies. Immunoreactive cells were also observed in the pituitary of 6 human anencephalic fetuses."}
{"id": "PMID:206384", "title": "Recurrent nocturnal asthma due to tolylene di-isocyanate: a case report.", "content": "In a carpenter with a history of nocturnal dyspnoea, a bronchial provocation test with a tolylene di-isocyanate (TDI) activator elicited a non-immediate asthmatic reaction, followed by recurrent nocturnal asthma for five subsequent nights. Subsequently, the study of the circadian rhythm of airflow, registered during work, confirmed the presence of recurrent nocturnal asthma of occupational origin.", "contents": "Recurrent nocturnal asthma due to tolylene di-isocyanate: a case report. In a carpenter with a history of nocturnal dyspnoea, a bronchial provocation test with a tolylene di-isocyanate (TDI) activator elicited a non-immediate asthmatic reaction, followed by recurrent nocturnal asthma for five subsequent nights. Subsequently, the study of the circadian rhythm of airflow, registered during work, confirmed the presence of recurrent nocturnal asthma of occupational origin."}
{"id": "PMID:206386", "title": "Two-point determination of plasma ammonia with the centrifugal analyzer.", "content": "A simple, convenient, and rapid method for determining ammonia in plasma by the glutamate dehydrogenase reaction is described for the centrifugal analyzer. The measuring principle is fixed-time, with NADH as the coenzyme. ADP is added to stabilize glutamate dehydrogenase and prevent interference from endogenous plasma ADP. The reaction is linear to 400 mumol of ammonia per liter. The plasma sample volume is 100 microliter and the whole procedure takes only 25 min, including the 15-min preincubation. The normal range for venous plasma was 44 +/- 13.5 (SD) mumol of ammonia per liter.", "contents": "Two-point determination of plasma ammonia with the centrifugal analyzer. A simple, convenient, and rapid method for determining ammonia in plasma by the glutamate dehydrogenase reaction is described for the centrifugal analyzer. The measuring principle is fixed-time, with NADH as the coenzyme. ADP is added to stabilize glutamate dehydrogenase and prevent interference from endogenous plasma ADP. The reaction is linear to 400 mumol of ammonia per liter. The plasma sample volume is 100 microliter and the whole procedure takes only 25 min, including the 15-min preincubation. The normal range for venous plasma was 44 +/- 13.5 (SD) mumol of ammonia per liter."}
{"id": "PMID:206387", "title": "N-Ethylmaleimide prevents destruction of corticotropin (ACTH) in plasma.", "content": "Addition of N-ethylmaleimide, an inhibitor of proteolytic enzymes, to samples for plasma corticotropin determinations prevents destruction of the hormone at room temperature for at least 72 h. A concentration of 125 mg per liter of blood is effective. N-Ethylmaleimide is not so effective in preventing corticotropin degradation in whole blood. Use of the inhibitor should make plasma corticotropin determinations more practical and reliable.", "contents": "N-Ethylmaleimide prevents destruction of corticotropin (ACTH) in plasma. Addition of N-ethylmaleimide, an inhibitor of proteolytic enzymes, to samples for plasma corticotropin determinations prevents destruction of the hormone at room temperature for at least 72 h. A concentration of 125 mg per liter of blood is effective. N-Ethylmaleimide is not so effective in preventing corticotropin degradation in whole blood. Use of the inhibitor should make plasma corticotropin determinations more practical and reliable."}
{"id": "PMID:206388", "title": "Cholinesterase in serum and low density lipoprotein of hyperlipidemic patients.", "content": "Cholinesterase activity in the low density lipoprotein fraction of serum is increased in types IIa, IIb and IV hyperlipoproteinemic patients, whereas only types IIb and IV show increases in serum cholinesterase activity. In obese patients, cholinesterase activity is increased both in the serum and low density lipoprotein fraction only when hyperlipidemia is present. Cholinesterase activity is also found to increase in proportion with increases in low density lipoprotein, cholesterol, and triglycerides both in the serum and low density lipoprotein fraction. We suggest on the basis of these findings that cholinesterase has a function in lipid and lipoprotein metabolism.", "contents": "Cholinesterase in serum and low density lipoprotein of hyperlipidemic patients. Cholinesterase activity in the low density lipoprotein fraction of serum is increased in types IIa, IIb and IV hyperlipoproteinemic patients, whereas only types IIb and IV show increases in serum cholinesterase activity. In obese patients, cholinesterase activity is increased both in the serum and low density lipoprotein fraction only when hyperlipidemia is present. Cholinesterase activity is also found to increase in proportion with increases in low density lipoprotein, cholesterol, and triglycerides both in the serum and low density lipoprotein fraction. We suggest on the basis of these findings that cholinesterase has a function in lipid and lipoprotein metabolism."}
{"id": "PMID:206390", "title": "Ultrastructural and steroidogenic characteristics of an androgen-producing adrenocortical tumour.", "content": "A 16-year-old female patient with an adrenal tumour was studied. Clinically she had progressive hirsutism, showed high urinary 17-oxosteroid excretion with normal plasma cortisol. Plasma C19-steroids, both unconjugated (including testosterone) and sulphate-conjugated, were greatly elevated. On surgical exploration an adrenal tumour was histologically an adenoma. On ultrastructural analysis the cells in all zones of the adjoining adrenal were considered normal. Although the tumour cells had the general appearance of a steroid-secreting cell their structure diverged from the cells of every subzone of the cortex. This was the case particularly with mitochondria and lipid inclusions. The  only endogenous unconjugated steroids detected in the adjoining cortex were corticosterone and cortisol while in tumour tissue these were present in lesser amounts. The tumour tissue contained large amounts of C19-steroids, 11beta-hydroxy-androstenedione being quantitatively most significant. On the basis of the steroid profile an impaired defect of 21-hydroxylation in tumour cells leading steroid synthesis from corticosteroidogenesis to the C19 pathway is proposed.", "contents": "Ultrastructural and steroidogenic characteristics of an androgen-producing adrenocortical tumour. A 16-year-old female patient with an adrenal tumour was studied. Clinically she had progressive hirsutism, showed high urinary 17-oxosteroid excretion with normal plasma cortisol. Plasma C19-steroids, both unconjugated (including testosterone) and sulphate-conjugated, were greatly elevated. On surgical exploration an adrenal tumour was histologically an adenoma. On ultrastructural analysis the cells in all zones of the adjoining adrenal were considered normal. Although the tumour cells had the general appearance of a steroid-secreting cell their structure diverged from the cells of every subzone of the cortex. This was the case particularly with mitochondria and lipid inclusions. The  only endogenous unconjugated steroids detected in the adjoining cortex were corticosterone and cortisol while in tumour tissue these were present in lesser amounts. The tumour tissue contained large amounts of C19-steroids, 11beta-hydroxy-androstenedione being quantitatively most significant. On the basis of the steroid profile an impaired defect of 21-hydroxylation in tumour cells leading steroid synthesis from corticosteroidogenesis to the C19 pathway is proposed."}
{"id": "PMID:206391", "title": "Growth retardation, skeletal maturation and thyroid function in children with homozygous beta-thalassaemia.", "content": "Growth rate, skeletal maturation and thyroid function were measured in fifty thalassaemic children (age 2-13 years) and in fifty controls (matched for sex and age who were not anaemic. Growth retardation was present in several patients during the first years of life and affected almost all subjects examined when they were approaching puberty. Discrepancy between bone and height age in patients was not significantly different from controls. The finding of low T4 and T3 with a high TSH indicated thyroid hypofunction. This finding, already present early in life, did not worsen with increasing age. In beta-thalassaemia hypothyroidism cannot be the cause of retarded growth since there is no relationship between the impairment in thyroid function and severity of growth retardation. In addition, height age was not different from bone age, while a discrepancy is a constant feature of low stature due to hypothyroidism.", "contents": "Growth retardation, skeletal maturation and thyroid function in children with homozygous beta-thalassaemia. Growth rate, skeletal maturation and thyroid function were measured in fifty thalassaemic children (age 2-13 years) and in fifty controls (matched for sex and age who were not anaemic. Growth retardation was present in several patients during the first years of life and affected almost all subjects examined when they were approaching puberty. Discrepancy between bone and height age in patients was not significantly different from controls. The finding of low T4 and T3 with a high TSH indicated thyroid hypofunction. This finding, already present early in life, did not worsen with increasing age. In beta-thalassaemia hypothyroidism cannot be the cause of retarded growth since there is no relationship between the impairment in thyroid function and severity of growth retardation. In addition, height age was not different from bone age, while a discrepancy is a constant feature of low stature due to hypothyroidism."}
{"id": "PMID:206396", "title": "Swan mice: autoimmune mice without xenotropic type C virus production.", "content": "Swan mice are characterized by various autoimmune disorders and the Swan disease resembles that of (NZB X NZW)F1 hybrids. A virological study of these animals shows that: (a) they do not produce xenotropic type C viruses at a detectable level; (b) old Swan mice can produce ecotropic type C virus but at a low level; and (c) this virus production and the appearance of antinuclear antibodies are dissociated in some mice. These results do not support the role of xenotropic type C viruses in murine autoimmune pathology. A possible role of ecotropic type C viruses cannot be definitely excluded, but appears unlikely.", "contents": "Swan mice: autoimmune mice without xenotropic type C virus production. Swan mice are characterized by various autoimmune disorders and the Swan disease resembles that of (NZB X NZW)F1 hybrids. A virological study of these animals shows that: (a) they do not produce xenotropic type C viruses at a detectable level; (b) old Swan mice can produce ecotropic type C virus but at a low level; and (c) this virus production and the appearance of antinuclear antibodies are dissociated in some mice. These results do not support the role of xenotropic type C viruses in murine autoimmune pathology. A possible role of ecotropic type C viruses cannot be definitely excluded, but appears unlikely."}
{"id": "PMID:206402", "title": "Effect of glucocorticoids and ACTH on antipyrine clearance in children.", "content": "Administration of dexamethasone and infusion of adrenocorticotropic hormone (ACTH) to children for periods up to 4 days did not alter the half-life, apparent volume of distribution, or metabolic clearance rate of antipyrine, a drug principally metabolized by the mixed-function oxidase system of the liver. We conclude that the short-term administration of glucocorticoids and ACTH with ensuing stimulation of endogenous glucocorticoid production is unlikely to produce clinically significant changes in the rate of drug metabolism.", "contents": "Effect of glucocorticoids and ACTH on antipyrine clearance in children. Administration of dexamethasone and infusion of adrenocorticotropic hormone (ACTH) to children for periods up to 4 days did not alter the half-life, apparent volume of distribution, or metabolic clearance rate of antipyrine, a drug principally metabolized by the mixed-function oxidase system of the liver. We conclude that the short-term administration of glucocorticoids and ACTH with ensuing stimulation of endogenous glucocorticoid production is unlikely to produce clinically significant changes in the rate of drug metabolism."}
{"id": "PMID:206412", "title": "Assignment of the gene for adenosine kinase to chromosome 14 in Mus musculus by somatic cell hybridization.", "content": "Evidence is presented for the assignment of the gene for adenosine kinase to Mus musculus chromosome 14 by synteny testing and karyotypic analysis of mouse X Chinese hamster somatic cell hybrid clones. ADOK and two enzymes previously mapped to mouse chromosome 14, NP and ES-10, were expressed concordantly in 29 hybrid clones. Chromosome analysis confirmed this assignment. Syntenic evidence is also presented using several clones of a gene transfer system in which the gene for human HPRT had integrated into modified mouse chromosome 14's.", "contents": "Assignment of the gene for adenosine kinase to chromosome 14 in Mus musculus by somatic cell hybridization. Evidence is presented for the assignment of the gene for adenosine kinase to Mus musculus chromosome 14 by synteny testing and karyotypic analysis of mouse X Chinese hamster somatic cell hybrid clones. ADOK and two enzymes previously mapped to mouse chromosome 14, NP and ES-10, were expressed concordantly in 29 hybrid clones. Chromosome analysis confirmed this assignment. Syntenic evidence is also presented using several clones of a gene transfer system in which the gene for human HPRT had integrated into modified mouse chromosome 14's."}
{"id": "PMID:206414", "title": "Inflammatory fibrous histiocytoma of the bronchus.", "content": "A 33 year-old woman underwent lobectomy of the middle and lower lobes of the right lung because of inflammatory fibrous histiocytoma of the bronchus. To our knowledge, this is the first description of such a tumor originating in the bronchus.", "contents": "Inflammatory fibrous histiocytoma of the bronchus. A 33 year-old woman underwent lobectomy of the middle and lower lobes of the right lung because of inflammatory fibrous histiocytoma of the bronchus. To our knowledge, this is the first description of such a tumor originating in the bronchus."}
{"id": "PMID:206415", "title": "Inflammatory changes related to active tuberculosis: confusion with oat cell carcinoma of the lung on cytology specimens.", "content": "One case of small cell lung carcinoma diagnosed on cytology specimens could not be confirmed histologically. We feel this likely represents cytopathologic changes induced in response to the patient's active tuberculosis. To avoid aggressive systemic therapy in such cases, patients with localized lesions should have further diagnostic procedures to confirm the cytologic diagnosis histologically.", "contents": "Inflammatory changes related to active tuberculosis: confusion with oat cell carcinoma of the lung on cytology specimens. One case of small cell lung carcinoma diagnosed on cytology specimens could not be confirmed histologically. We feel this likely represents cytopathologic changes induced in response to the patient's active tuberculosis. To avoid aggressive systemic therapy in such cases, patients with localized lesions should have further diagnostic procedures to confirm the cytologic diagnosis histologically."}
{"id": "PMID:206424", "title": "[Differential diagnosis of hypothalamic-hypophyseal Cushing's syndrome and ectopic ACTH syndrome (author's transl)].", "content": "Endocrinological symptoms of, on the one hand, hypothalamic-hypophyseal Cushing's syndrome and, on the other, ectopic ACTH syndrome (usually caused by bronchial carcinoma) can often not be distinguished. Reliable differentiation of these two forms of secondary hypercortisolism is necessary, because in hypothalamic-hypophyseal Cushing's syndrome therapy is more and more frequently directed at the anterior pituitary and hypothalamus rather than attempted by bilateral adrenalectomy. The following method was used for distinguishing between the two in six patients: blood was withdrawn by catheter from the jugular vein and the inferior petrosal sinus and the ACTH concentrations measured. Compared with ACTH concentration in a peripheral vein (e.g. cubital vein) that in the jugular vein was higher in five patients by a factor of 1.47 +/- 0.1 and in the inferior petrosal sinus by 2.39 +/- 0.64. A positive diagnosis of hypothalamic-hypophyseal Cushing's syndrome can thus be made. In one patient the diagnosis of ectopic ACTH syndrome could be made from the gradient of ACTH concentration between the cardiac right ventricle and the bronchial artery (1 : 3.75), before there was radiological demonstration of the bronchial carcinoma.", "contents": "[Differential diagnosis of hypothalamic-hypophyseal Cushing's syndrome and ectopic ACTH syndrome (author's transl)]. Endocrinological symptoms of, on the one hand, hypothalamic-hypophyseal Cushing's syndrome and, on the other, ectopic ACTH syndrome (usually caused by bronchial carcinoma) can often not be distinguished. Reliable differentiation of these two forms of secondary hypercortisolism is necessary, because in hypothalamic-hypophyseal Cushing's syndrome therapy is more and more frequently directed at the anterior pituitary and hypothalamus rather than attempted by bilateral adrenalectomy. The following method was used for distinguishing between the two in six patients: blood was withdrawn by catheter from the jugular vein and the inferior petrosal sinus and the ACTH concentrations measured. Compared with ACTH concentration in a peripheral vein (e.g. cubital vein) that in the jugular vein was higher in five patients by a factor of 1.47 +/- 0.1 and in the inferior petrosal sinus by 2.39 +/- 0.64. A positive diagnosis of hypothalamic-hypophyseal Cushing's syndrome can thus be made. In one patient the diagnosis of ectopic ACTH syndrome could be made from the gradient of ACTH concentration between the cardiac right ventricle and the bronchial artery (1 : 3.75), before there was radiological demonstration of the bronchial carcinoma."}
{"id": "PMID:206427", "title": "Metabolic effects of some antibilharzial drugs: inhibition of NAD-linked substrate oxidation in rat liver by bilharcid.", "content": "BILHARCID inhibited malate and pyruvate oxidation. The degree of inhibition reached 50% when the concentration of Bilharcid was 10(-3) M. The mechanisms of the inhibitory action of the drug are discussed with reference to the effects of both adenine and pyridine nucleotides on the activity of the oxidoreductase enzymes.", "contents": "Metabolic effects of some antibilharzial drugs: inhibition of NAD-linked substrate oxidation in rat liver by bilharcid. BILHARCID inhibited malate and pyruvate oxidation. The degree of inhibition reached 50% when the concentration of Bilharcid was 10(-3) M. The mechanisms of the inhibitory action of the drug are discussed with reference to the effects of both adenine and pyridine nucleotides on the activity of the oxidoreductase enzymes."}
{"id": "PMID:206428", "title": "Carcinogenicity studies on halogenated hydrocarbons.", "content": "A series of halogenated compounds was tested by oral intubation in 200 Osborne-Mendel rats and 200 B6C3F1 mice of both sexes. Carbon tetrachloride, used as a positive control, induced liver and adrenal tumors in mice and neoplastic nodules in the livers of rats. 1,2-Dibromoethane and 1,2-dibromo-3-chloropropane caused stomach tumors with many metastases in both rats and mice. Chloroform, known to cause hepatocellular carcinomas in mice, led in addition to kidney tumors in male rats. 1,2-Dichloroethane was much weaker than the analog, 1,2-dibromoethane, and induced only a few stomach tumors in rats. It increased liver and lung tumors in mice. Most of the compounds, namely, trichloroethylene, 1,1-dichloroethane, 1,1,2-trichloroethane, hexachloroethane, and tetrachloroethylene, increased hepatocellular carcinomas in mice but had little or no action in rats. Iodoform tended to increase thyroid tumors in male rats and hepatocellular carcinomas in male mice. The action of 3-chloropropene was questionable. No tumors could be attributed to 1,1,1-trichloroethane (methyl-chloroform).", "contents": "Carcinogenicity studies on halogenated hydrocarbons. A series of halogenated compounds was tested by oral intubation in 200 Osborne-Mendel rats and 200 B6C3F1 mice of both sexes. Carbon tetrachloride, used as a positive control, induced liver and adrenal tumors in mice and neoplastic nodules in the livers of rats. 1,2-Dibromoethane and 1,2-dibromo-3-chloropropane caused stomach tumors with many metastases in both rats and mice. Chloroform, known to cause hepatocellular carcinomas in mice, led in addition to kidney tumors in male rats. 1,2-Dichloroethane was much weaker than the analog, 1,2-dibromoethane, and induced only a few stomach tumors in rats. It increased liver and lung tumors in mice. Most of the compounds, namely, trichloroethylene, 1,1-dichloroethane, 1,1,2-trichloroethane, hexachloroethane, and tetrachloroethylene, increased hepatocellular carcinomas in mice but had little or no action in rats. Iodoform tended to increase thyroid tumors in male rats and hepatocellular carcinomas in male mice. The action of 3-chloropropene was questionable. No tumors could be attributed to 1,1,1-trichloroethane (methyl-chloroform)."}
{"id": "PMID:206430", "title": "Synthesis of an oligonucleotide inhibitor of protein synthesis in rabbit reticulocyte lysates analogous to that formed in extracts from interferon-treated cells.", "content": "A heat-stable, low-molecular-weight inhibitor of protein synthesis is formed on incubation of haemin-supplemented rabbit reticulocyte lysates with ATP and double-stranded RNA (dsRNA). It inhibits the translation of both added encephalomyocarditis virus RNA (EMC RNA) and endogeneous messenger RNA in reticulocyte lysates and mouse L-cell extracts. The enzyme responsible for the synthesis of the inhibitor binds to dsRNA and can be purified on a column of poly(I).poly (C) bound to an inert support. The highly purified enzyme in its stable column-bound state can be conveniently employed to synthesise the inhibitor and to label it with [3H]ATP, or [alpha-32P]ATP or [gamma-32P]ATP as substrate. The radioactive inhibitor synthesised in this way with material from rabbit reticulocyte lysates shows the same spectrum of resistance and sensitivity to alkali and a variety of enzymes as corresponding material similarly synthesised with extracts from interferon-treated mouse L-cells. The inhibitors from the two systems have comparable absorbance spectra, are chromatographically and electrophoretically indistinguishable and are apparently identical in specific activity in the inhibition of protein synthesis in the cell-free system. The inhibitor is also formed on inhibition of protein synthesis by dsRNA in reticulocyte lysates. On comparison of the spectrum of polypeptide products synthesised in response to EMC RNA in the reticulocyte lysate, the effects of the inhibitor or dsRNA were similar: a distinctly different effect was obtained with the haemin-controlled repressor, a known inhibitor of initiation. The significance of these results with respect to the mechanism of action of the inhibitor and its role in the inhibition observed in response to dsRNA is discussed.", "contents": "Synthesis of an oligonucleotide inhibitor of protein synthesis in rabbit reticulocyte lysates analogous to that formed in extracts from interferon-treated cells. A heat-stable, low-molecular-weight inhibitor of protein synthesis is formed on incubation of haemin-supplemented rabbit reticulocyte lysates with ATP and double-stranded RNA (dsRNA). It inhibits the translation of both added encephalomyocarditis virus RNA (EMC RNA) and endogeneous messenger RNA in reticulocyte lysates and mouse L-cell extracts. The enzyme responsible for the synthesis of the inhibitor binds to dsRNA and can be purified on a column of poly(I).poly (C) bound to an inert support. The highly purified enzyme in its stable column-bound state can be conveniently employed to synthesise the inhibitor and to label it with [3H]ATP, or [alpha-32P]ATP or [gamma-32P]ATP as substrate. The radioactive inhibitor synthesised in this way with material from rabbit reticulocyte lysates shows the same spectrum of resistance and sensitivity to alkali and a variety of enzymes as corresponding material similarly synthesised with extracts from interferon-treated mouse L-cells. The inhibitors from the two systems have comparable absorbance spectra, are chromatographically and electrophoretically indistinguishable and are apparently identical in specific activity in the inhibition of protein synthesis in the cell-free system. The inhibitor is also formed on inhibition of protein synthesis by dsRNA in reticulocyte lysates. On comparison of the spectrum of polypeptide products synthesised in response to EMC RNA in the reticulocyte lysate, the effects of the inhibitor or dsRNA were similar: a distinctly different effect was obtained with the haemin-controlled repressor, a known inhibitor of initiation. The significance of these results with respect to the mechanism of action of the inhibitor and its role in the inhibition observed in response to dsRNA is discussed."}
{"id": "PMID:206431", "title": "The linear electric field effect in stellacyanin, azurin and in some simple model compounds.", "content": "All mononuclear Cu(II) sites in frozen solution are non-centrosymmetric and, unless physically constrained, will have a tetrahedral distortion away from the usual square planar structure often presented for Cu(II) complexes. Blue copper sites such as are found in azurin and stellacyanin have a greater distortion towards a tetrahedral geometry than do simple Cu(II) complexes. The distortion is comparable to that which is observed for Cu(II)-o-phenanthroline dichloride, a known tetrahedral complex. Blue copper sites possess an axis of asymmetry directed away from g parallel which could arise from a metal-sulfur interaction.", "contents": "The linear electric field effect in stellacyanin, azurin and in some simple model compounds. All mononuclear Cu(II) sites in frozen solution are non-centrosymmetric and, unless physically constrained, will have a tetrahedral distortion away from the usual square planar structure often presented for Cu(II) complexes. Blue copper sites such as are found in azurin and stellacyanin have a greater distortion towards a tetrahedral geometry than do simple Cu(II) complexes. The distortion is comparable to that which is observed for Cu(II)-o-phenanthroline dichloride, a known tetrahedral complex. Blue copper sites possess an axis of asymmetry directed away from g parallel which could arise from a metal-sulfur interaction."}
{"id": "PMID:206437", "title": "Electron transport in the cni-1 mutant of Neurospora crassa.", "content": "1. Mitochondria from the nuclear mutant cni-1 have no optically detectable cytochrome aa3 in early log phase growth. These mitochondria have a high level of respiration that is not inhibited by cyanide but is inhibited by salicylhydroxamic acid. They also show a substantial amount of cyanide-sensitive respiration. 2. As cultures of mutant cni-1 age, flux through the hydroxamate-sensitive pathway decreases markedly while flux through the cytochrome chain remains constant. 3. Growth studies with mutant cni-1 indicate that the cytochrome chain in this mutant is more important in supporting growth than the hydroxamate-sensitive pathway. 4. Measurements of the steady-state level of reduction of cytochrome c in mutant cni-1 indicate that the rate-limiting step in the cytochrome chain is at the position occupied by cytochrome oxidase. 5. Electron spin resonance studies with cni-1 mitochondria show normal cytochrome oxidase signals in the g approximately 6 region although there is little or no optically detectable cytochrome aa3.", "contents": "Electron transport in the cni-1 mutant of Neurospora crassa. 1. Mitochondria from the nuclear mutant cni-1 have no optically detectable cytochrome aa3 in early log phase growth. These mitochondria have a high level of respiration that is not inhibited by cyanide but is inhibited by salicylhydroxamic acid. They also show a substantial amount of cyanide-sensitive respiration. 2. As cultures of mutant cni-1 age, flux through the hydroxamate-sensitive pathway decreases markedly while flux through the cytochrome chain remains constant. 3. Growth studies with mutant cni-1 indicate that the cytochrome chain in this mutant is more important in supporting growth than the hydroxamate-sensitive pathway. 4. Measurements of the steady-state level of reduction of cytochrome c in mutant cni-1 indicate that the rate-limiting step in the cytochrome chain is at the position occupied by cytochrome oxidase. 5. Electron spin resonance studies with cni-1 mitochondria show normal cytochrome oxidase signals in the g approximately 6 region although there is little or no optically detectable cytochrome aa3."}
{"id": "PMID:206438", "title": "Thermal regulation of the fatty acid composition of lipopolysaccharides and phospholipids of Proteus mirabilis.", "content": "The fatty acid composition of the lipid A moiety of the lipopolysaccharide and phospholipid fractions of Proteus mirabilis changed significantly on varying the growth temperature. A decrease in the growth temperature from 43 degrees C to 15 degrees C resulted in a decrease in the palmitic acid content of the lipopolysaccharide from 19.4% of total fatty acids at 43 degrees C to 1.4% at 15 degrees C, and by the appearance of an unsaturated fatty acid residue, hexadecenoic acid. Changes in the 3-hydroxy-myristic acid content of the lipid A were minimal. The decrease in the growth temperature also resulted in a decrease in the saturated fatty acid content of the phospholipid fraction, which was accompanied by an increase in their fluidity, as measured by the freedom of motion of spin-labeled fatty acids incorporated into dispersions made of the phospholipids. Nevertheless, the fluidity obtained with membrane phospholipids extracted from the cells grown at various temperatures were essentially the same when fluidity was determined at the growth temperature, supporting the hypothesis that variations in the fatty acid composition of membrane phospholipids serve to produce membranes having a constant fluidity at different temperatures of growth.", "contents": "Thermal regulation of the fatty acid composition of lipopolysaccharides and phospholipids of Proteus mirabilis. The fatty acid composition of the lipid A moiety of the lipopolysaccharide and phospholipid fractions of Proteus mirabilis changed significantly on varying the growth temperature. A decrease in the growth temperature from 43 degrees C to 15 degrees C resulted in a decrease in the palmitic acid content of the lipopolysaccharide from 19.4% of total fatty acids at 43 degrees C to 1.4% at 15 degrees C, and by the appearance of an unsaturated fatty acid residue, hexadecenoic acid. Changes in the 3-hydroxy-myristic acid content of the lipid A were minimal. The decrease in the growth temperature also resulted in a decrease in the saturated fatty acid content of the phospholipid fraction, which was accompanied by an increase in their fluidity, as measured by the freedom of motion of spin-labeled fatty acids incorporated into dispersions made of the phospholipids. Nevertheless, the fluidity obtained with membrane phospholipids extracted from the cells grown at various temperatures were essentially the same when fluidity was determined at the growth temperature, supporting the hypothesis that variations in the fatty acid composition of membrane phospholipids serve to produce membranes having a constant fluidity at different temperatures of growth."}
{"id": "PMID:206439", "title": "Translation of encephalomyocarditis virus RNA in vitro yields an active proteolytic processing enzyme.", "content": "In contrast to other cell-free translation systems, the mRNA-dependent reticulocyte lysate can translate encephalomyocarditis virus RNA efficiently and completely when supplemented with heterologous tRNA. Cleavage of the nascent polypeptide chain occurs, and one of the translation products appears to be a specific proteolytic enzyme which correctly processes the primary products. The identity of the proteins made in vitro was verified by comparison with infected cell proteins on dodecylsulphate/polyacrylamide gels, and by mapping their coding sequences on the viral genome.", "contents": "Translation of encephalomyocarditis virus RNA in vitro yields an active proteolytic processing enzyme. In contrast to other cell-free translation systems, the mRNA-dependent reticulocyte lysate can translate encephalomyocarditis virus RNA efficiently and completely when supplemented with heterologous tRNA. Cleavage of the nascent polypeptide chain occurs, and one of the translation products appears to be a specific proteolytic enzyme which correctly processes the primary products. The identity of the proteins made in vitro was verified by comparison with infected cell proteins on dodecylsulphate/polyacrylamide gels, and by mapping their coding sequences on the viral genome."}
{"id": "PMID:206440", "title": "Purification and characterization of DNA polymerases from the plasmacytoma MOPC 104E and Abelson murine leukemia viruses.", "content": "RNA-dependent DNA polymerases of intracisternal A particles from the mouse plasma cell tumor MOPC 104E and of Abelson murine leukemia virus (A-MuLV) were isolated from particle preparations by Nonidet P40 and ultrasonic treatment and purified by column chromatography on DEAE-cellulose and phosphocellulose, followed by centrifugation in linear sucrose gradients. Both DNA polymerases were very similar in their elution patterns from phospho and DEAE-cellulose, template specificities, requirements for optimum activity and inactivation by anti-(reverse transcriptase) antiserum. They are associated with ribonuclease H activity. For molecular weight determinations, antibody-precipitated enzymes were bound to staphylococcal-protein-A-Sepharose, solubilized and run on dodecylsulfate/polyacrylamide gels. Their apparent molecular weight was estimated to be 80000.", "contents": "Purification and characterization of DNA polymerases from the plasmacytoma MOPC 104E and Abelson murine leukemia viruses. RNA-dependent DNA polymerases of intracisternal A particles from the mouse plasma cell tumor MOPC 104E and of Abelson murine leukemia virus (A-MuLV) were isolated from particle preparations by Nonidet P40 and ultrasonic treatment and purified by column chromatography on DEAE-cellulose and phosphocellulose, followed by centrifugation in linear sucrose gradients. Both DNA polymerases were very similar in their elution patterns from phospho and DEAE-cellulose, template specificities, requirements for optimum activity and inactivation by anti-(reverse transcriptase) antiserum. They are associated with ribonuclease H activity. For molecular weight determinations, antibody-precipitated enzymes were bound to staphylococcal-protein-A-Sepharose, solubilized and run on dodecylsulfate/polyacrylamide gels. Their apparent molecular weight was estimated to be 80000."}
{"id": "PMID:206441", "title": "Endotoxin stimulated nitroblue-tetrazolium (NBT)-test in patients with hypoparathyroidism, pseudohypoparathyroidism and other forms of hypocalcemia.", "content": "Endotoxin-stimulated NBT-tests were carried out in 15 patients with hypocalcemia of varying etiology and in 14 normocalcemic children free of infection. In the control group the formazan cell percentage (FCP) was 73.8 +/- 1.6% (range 63% to 83%). In 5 patients with hypoparathyroidism or pseudohypoparathyroidism the FCP before treatment was lower than normal. Vitamin D3 therapy produced a rapid increase of serum calcium but normalisation of NBT-test was only achieved after a latent period of one or more months. Patients with hypocalcemic rickets and children with an acute relapse of the nephrotic syndrome also showed abnormal results. The clinical significance of the NBT-test in hypocalcemic conditions is discussed.", "contents": "Endotoxin stimulated nitroblue-tetrazolium (NBT)-test in patients with hypoparathyroidism, pseudohypoparathyroidism and other forms of hypocalcemia. Endotoxin-stimulated NBT-tests were carried out in 15 patients with hypocalcemia of varying etiology and in 14 normocalcemic children free of infection. In the control group the formazan cell percentage (FCP) was 73.8 +/- 1.6% (range 63% to 83%). In 5 patients with hypoparathyroidism or pseudohypoparathyroidism the FCP before treatment was lower than normal. Vitamin D3 therapy produced a rapid increase of serum calcium but normalisation of NBT-test was only achieved after a latent period of one or more months. Patients with hypocalcemic rickets and children with an acute relapse of the nephrotic syndrome also showed abnormal results. The clinical significance of the NBT-test in hypocalcemic conditions is discussed."}
{"id": "PMID:206442", "title": "Wilms' tumor and adrenocortical carcinoma with hemihypertrophy and hamartomas.", "content": "A girl with hemihypertrophy and hamartomas, now 14 years old, had Wilms' tumor and subsequently developed adrenocortical carcinoma. The occurrence of the two tumors with the signs of an inborn defect of growth control supports the hypothesis that both tumors can be caused by the same etiologic factors, which are also teratogenic. An alternative explanation of induction of the second tumor by previous radio- and chemotherapy is discussed. Possible relationships between our case and the syndrome of Wiedemann and Beckwith are pointed out.", "contents": "Wilms' tumor and adrenocortical carcinoma with hemihypertrophy and hamartomas. A girl with hemihypertrophy and hamartomas, now 14 years old, had Wilms' tumor and subsequently developed adrenocortical carcinoma. The occurrence of the two tumors with the signs of an inborn defect of growth control supports the hypothesis that both tumors can be caused by the same etiologic factors, which are also teratogenic. An alternative explanation of induction of the second tumor by previous radio- and chemotherapy is discussed. Possible relationships between our case and the syndrome of Wiedemann and Beckwith are pointed out."}
{"id": "PMID:206446", "title": "Hepatic collagen proline hydroxylase activity in primary biliary cirrhosis.", "content": "The enzyme collagen proline hydroxylase has been measured in liver biopsies from fourteen patients with primary biliary cirrhosis. The activity was elevated in ten of the patients, but not to the degree previously found in patients with active cirrhosis. There was no correlation between the enzyme activity and the liver copper concentration, which was elevated in all except one of those measured. This suggests that excessive collagen synthesis in PBC is not directly related to the high liver copper concentrations.", "contents": "Hepatic collagen proline hydroxylase activity in primary biliary cirrhosis. The enzyme collagen proline hydroxylase has been measured in liver biopsies from fourteen patients with primary biliary cirrhosis. The activity was elevated in ten of the patients, but not to the degree previously found in patients with active cirrhosis. There was no correlation between the enzyme activity and the liver copper concentration, which was elevated in all except one of those measured. This suggests that excessive collagen synthesis in PBC is not directly related to the high liver copper concentrations."}
{"id": "PMID:206449", "title": "Responses of the canine hepatic arterial and portal venous vascular beds to dopamine.", "content": "Dopamine was injected in graded doses into the hepatic artery of the anaesthetized dog: the typical response was an initial vasoconstriction followed by a more protracted vasodilatation. The vasodilatation was unaffected by propranolol, but was antagonized by haloperidol. The initial hepatic arterial vasoconstriction was inhibited both by haloperidol and by phentolamine. The experiments suggest that the initial vasoconstriction was due to alpha-adrenoceptor stimulation and that the secondary vasodilatation was the result of the stimulation of dopamine receptors. In separate experiments, dopamine was injected into the hepatic portal vein of the dog. The only response seen was a dose-dependent portal vasoconstriction which was antagonized both by haloperidol and by phentolamine. Since both of these antagonists attenuated the portal vasoconstrictor effects of intraportal phenylephrine, it is probable that the portal vasoconstriction effect of dopamine is due to alpha-adrenoceptor stimulation.", "contents": "Responses of the canine hepatic arterial and portal venous vascular beds to dopamine. Dopamine was injected in graded doses into the hepatic artery of the anaesthetized dog: the typical response was an initial vasoconstriction followed by a more protracted vasodilatation. The vasodilatation was unaffected by propranolol, but was antagonized by haloperidol. The initial hepatic arterial vasoconstriction was inhibited both by haloperidol and by phentolamine. The experiments suggest that the initial vasoconstriction was due to alpha-adrenoceptor stimulation and that the secondary vasodilatation was the result of the stimulation of dopamine receptors. In separate experiments, dopamine was injected into the hepatic portal vein of the dog. The only response seen was a dose-dependent portal vasoconstriction which was antagonized both by haloperidol and by phentolamine. Since both of these antagonists attenuated the portal vasoconstrictor effects of intraportal phenylephrine, it is probable that the portal vasoconstriction effect of dopamine is due to alpha-adrenoceptor stimulation."}
{"id": "PMID:206450", "title": "Isoproterenol-stimulated taurine influx in the perfused rat heart.", "content": "Taurine influx in the perfused rat heart was characterized and the effect of isoproterenol on this process determined. Hearts were perfused by the Langendorff technique with [3H]-taurine in a non-recirculating system. The rate of taurine influx was constant for at least 20 min and the process was saturable. A Km of 45 micron indicated that taurine influx is mediated by a high affinity transport system. Competition between taurine and beta-alanine, but not alpha-amino acids, for influx indicated that the transport sites are specific for beta-amino acids. Isoproterenol (4 X 10(-7) M) stimulated the rate of taurine influx, but propranolol (1 X 10(-8) M) blocked this stimulation. The enhancement of influx by isoproterenol was specific for beta-amino acids in that alpha-amino acid influx was not affected. Dibutyryl cyclic AMP (1 X 10(-3) M) and theophylline (1 X 10(-3) M) also stimulated taurine influx, whereas alterations in heart rate had no effect on the rate of taurine influx. The results are suggestive of a beta-adrenergically activated, cyclic AMP-mediated mechanism controlling isoproterenol-stimulated taurine influx.", "contents": "Isoproterenol-stimulated taurine influx in the perfused rat heart. Taurine influx in the perfused rat heart was characterized and the effect of isoproterenol on this process determined. Hearts were perfused by the Langendorff technique with [3H]-taurine in a non-recirculating system. The rate of taurine influx was constant for at least 20 min and the process was saturable. A Km of 45 micron indicated that taurine influx is mediated by a high affinity transport system. Competition between taurine and beta-alanine, but not alpha-amino acids, for influx indicated that the transport sites are specific for beta-amino acids. Isoproterenol (4 X 10(-7) M) stimulated the rate of taurine influx, but propranolol (1 X 10(-8) M) blocked this stimulation. The enhancement of influx by isoproterenol was specific for beta-amino acids in that alpha-amino acid influx was not affected. Dibutyryl cyclic AMP (1 X 10(-3) M) and theophylline (1 X 10(-3) M) also stimulated taurine influx, whereas alterations in heart rate had no effect on the rate of taurine influx. The results are suggestive of a beta-adrenergically activated, cyclic AMP-mediated mechanism controlling isoproterenol-stimulated taurine influx."}
{"id": "PMID:206451", "title": "FMRFamide increases the adenylate cyclase activity and cylic AMP level of molluscan heart.", "content": "FMRFamide (phenylalanyl-methionyl-arginyl-phenylalanine amide) is a cardioexcitatory peptide recently isolated and identified in molluscan ganglia. Both FMRFamide and 5-hydroxytryptamine (5HT), the cardioexcitatory neurotransmitter in molluscs, were tested on the ventricle of the bivalve Mercenaria mercenaria. Both agents increased myocardial contractility, the intracellular cyclic AMP concentration of intact hearts and the adenylate cyclase activity of a myocardial membrane fraction. FMRFamide was 5--10 times more potent than 5HT. All of the effects of 5HT, and none of those of FMRFamide, were blocked by methysergide, a specific 5HT antagonist.", "contents": "FMRFamide increases the adenylate cyclase activity and cylic AMP level of molluscan heart. FMRFamide (phenylalanyl-methionyl-arginyl-phenylalanine amide) is a cardioexcitatory peptide recently isolated and identified in molluscan ganglia. Both FMRFamide and 5-hydroxytryptamine (5HT), the cardioexcitatory neurotransmitter in molluscs, were tested on the ventricle of the bivalve Mercenaria mercenaria. Both agents increased myocardial contractility, the intracellular cyclic AMP concentration of intact hearts and the adenylate cyclase activity of a myocardial membrane fraction. FMRFamide was 5--10 times more potent than 5HT. All of the effects of 5HT, and none of those of FMRFamide, were blocked by methysergide, a specific 5HT antagonist."}
{"id": "PMID:206452", "title": "SEM observations on Sendai virus-induced fusion of embryonic mouse erythroblasts.", "content": "The events of fusion of 11- and 16-day embryonic mouse liver erythroblasts induced by Sendai virus (SV) were followed with the scanning electron microscope (SEM). Erythroid precursors incubated with the virus showed numerous 'pores' on the cell membrane. The cell fusion began with the appearance of a fine 'meshwork' structure between the adjacent cells, followed by a gradual formation of a common cell membrane and terminated with the appearance of polykaryons, in which the nuclei were easily recognized when located in the vicinity of the polykaryon membrane. There was no difference in the process of fusion between erythroblasts at identical and those at different stages of maturation.", "contents": "SEM observations on Sendai virus-induced fusion of embryonic mouse erythroblasts. The events of fusion of 11- and 16-day embryonic mouse liver erythroblasts induced by Sendai virus (SV) were followed with the scanning electron microscope (SEM). Erythroid precursors incubated with the virus showed numerous 'pores' on the cell membrane. The cell fusion began with the appearance of a fine 'meshwork' structure between the adjacent cells, followed by a gradual formation of a common cell membrane and terminated with the appearance of polykaryons, in which the nuclei were easily recognized when located in the vicinity of the polykaryon membrane. There was no difference in the process of fusion between erythroblasts at identical and those at different stages of maturation."}
{"id": "PMID:206453", "title": "Athymic nude mice: induction of tumors containing Epstein-Barr virus using Burkitt's-related cell lines.", "content": "We studied tumor induction in athymic nude mice by D98/HR-1 cells, an epithelial somatic cell hybrid containing the Epstein-Barr virus (EBV) genome, and by the parental D98 and HR-1 cells. Groups of animals were inoculated with cells grown in culture, with cells from tumors induced by the cell lines, or with cells from lines derived from tumors. The tumors induced by D98/HR-1 cells were undifferentiated carcinomas; those induced by D98 cells were carcinomas and those induced by HR-1 cells were poorly differentiated lymphomas. Preliminary data suggest that the number of EBV genome equivalents was sharply reduced in cells from both D98/HR-1 and HR-1 tumors. Subsequent passage of tumor cells in vitro resulted in a partial recovery in the number of EBV genome equivalents in HR-1 cells and a complete recovery in D98/HR-1 cells. The reduction in the number of EBV genomes in the tumor cells suggests that in vitro passage can influence the number of EBV genomes in these cells.", "contents": "Athymic nude mice: induction of tumors containing Epstein-Barr virus using Burkitt's-related cell lines. We studied tumor induction in athymic nude mice by D98/HR-1 cells, an epithelial somatic cell hybrid containing the Epstein-Barr virus (EBV) genome, and by the parental D98 and HR-1 cells. Groups of animals were inoculated with cells grown in culture, with cells from tumors induced by the cell lines, or with cells from lines derived from tumors. The tumors induced by D98/HR-1 cells were undifferentiated carcinomas; those induced by D98 cells were carcinomas and those induced by HR-1 cells were poorly differentiated lymphomas. Preliminary data suggest that the number of EBV genome equivalents was sharply reduced in cells from both D98/HR-1 and HR-1 tumors. Subsequent passage of tumor cells in vitro resulted in a partial recovery in the number of EBV genome equivalents in HR-1 cells and a complete recovery in D98/HR-1 cells. The reduction in the number of EBV genomes in the tumor cells suggests that in vitro passage can influence the number of EBV genomes in these cells."}
{"id": "PMID:206457", "title": "Plasma membrane involvement in brown fat thermogenesis.", "content": "Recent experiments indicate that plasma membranes of brown adipocytes contain distinct alpha- and beta-adrenergic receptors able to recognize norepinephrine. Although activation of either receptor leads to brown fat thermogenesis via pathways that have some, but not all, events in common, the beta-induced calorigenesis appears quantitatively greater than that elicited by the alpha-pathway. The sensitivity of the adrenergic-evoked respiration to Na+/K+ pump blockade as well as to atractyloside supports the view that a significant portion of brown fat thermogenesis reflects increased ATP turnover and enhanced mitochondrial ATP synthesis.", "contents": "Plasma membrane involvement in brown fat thermogenesis. Recent experiments indicate that plasma membranes of brown adipocytes contain distinct alpha- and beta-adrenergic receptors able to recognize norepinephrine. Although activation of either receptor leads to brown fat thermogenesis via pathways that have some, but not all, events in common, the beta-induced calorigenesis appears quantitatively greater than that elicited by the alpha-pathway. The sensitivity of the adrenergic-evoked respiration to Na+/K+ pump blockade as well as to atractyloside supports the view that a significant portion of brown fat thermogenesis reflects increased ATP turnover and enhanced mitochondrial ATP synthesis."}
{"id": "PMID:206463", "title": "Cytochrome c oxidase is not a proton pump.", "content": "We conclude that the reduction of O2 to 2 H2O by cytochrome c oxidase of rat liver mitochondria involves the translocation of 4-from cytochrome c at the outer surface of the cristae membrane per O2 reduced and protonated by 4 H+ ions that enter the reaction domain from the inner aqueous phase. This net electron-translocating function of cytochrome c oxidase plugged through the mitochondrial cristae membrane is not linked to a proton-pumping function, such as that proposed by Wikstr\u00f6m [7,8].", "contents": "Cytochrome c oxidase is not a proton pump. We conclude that the reduction of O2 to 2 H2O by cytochrome c oxidase of rat liver mitochondria involves the translocation of 4-from cytochrome c at the outer surface of the cristae membrane per O2 reduced and protonated by 4 H+ ions that enter the reaction domain from the inner aqueous phase. This net electron-translocating function of cytochrome c oxidase plugged through the mitochondrial cristae membrane is not linked to a proton-pumping function, such as that proposed by Wikstr\u00f6m [7,8]."}
{"id": "PMID:206470", "title": "Effect of prolactin on tetracycline binding to human spermatozoa.", "content": "The effect of different concentrations of prolactin (0 to 60 ng) on the release of tetracycline from human spermatozoa labeled with 7-3H-tetracycline hydrochloride was studied. Prolactin significantly enhanced the release of bound tetracycline, indicating that prolactin may influence the processes associated with sperm capacitation.", "contents": "Effect of prolactin on tetracycline binding to human spermatozoa. The effect of different concentrations of prolactin (0 to 60 ng) on the release of tetracycline from human spermatozoa labeled with 7-3H-tetracycline hydrochloride was studied. Prolactin significantly enhanced the release of bound tetracycline, indicating that prolactin may influence the processes associated with sperm capacitation."}
{"id": "PMID:206471", "title": "Calcium ion requirement for rabbit spermatozoal capacitation and enhancement of fertilizing ability by ionophore A23187 and cyclic adenosine 3':5'-monophosphate.", "content": "The presence of extracellular calcium is required for the in vitro occurrence of rabbit spermatozoal capacitation. However, calcium itself was found to be an inefficient agent for capacitating rabbit spermatozoa (following insemination with spermatozoa incubated for 10 hours in the presence of 2.5 X 10(-3) M calcium, only 9% of the ova cleaved). The addition of the divalent ionophore A23187 induced the early occurrence of capacitation and increased the percentage of full capacitated spermatozoa in a concentration-dependent manner (i.e, following insemination with spermatozoa incubated for 4 hours in the presence of 2.5 X 10(-3) M calcium and 2 X 10(-5) M A23187, 44% of the ova cleaved). Physiologic levels of capacitation were attained as estimated by the high proportion of ova that cleaved following in vitro insemination, when dibutyryl cyclic adenosine 3':5'-monophosphate (10(-6) m) was added in the presence of calcium (2.5 X 10(-3) M) and A23187 (2 X 10(-5) M) for treatment of spermatozoa.", "contents": "Calcium ion requirement for rabbit spermatozoal capacitation and enhancement of fertilizing ability by ionophore A23187 and cyclic adenosine 3':5'-monophosphate. The presence of extracellular calcium is required for the in vitro occurrence of rabbit spermatozoal capacitation. However, calcium itself was found to be an inefficient agent for capacitating rabbit spermatozoa (following insemination with spermatozoa incubated for 10 hours in the presence of 2.5 X 10(-3) M calcium, only 9% of the ova cleaved). The addition of the divalent ionophore A23187 induced the early occurrence of capacitation and increased the percentage of full capacitated spermatozoa in a concentration-dependent manner (i.e, following insemination with spermatozoa incubated for 4 hours in the presence of 2.5 X 10(-3) M calcium and 2 X 10(-5) M A23187, 44% of the ova cleaved). Physiologic levels of capacitation were attained as estimated by the high proportion of ova that cleaved following in vitro insemination, when dibutyryl cyclic adenosine 3':5'-monophosphate (10(-6) m) was added in the presence of calcium (2.5 X 10(-3) M) and A23187 (2 X 10(-5) M) for treatment of spermatozoa."}
{"id": "PMID:206473", "title": "[Effect of isadrine and propranolol on the membrane potential of mammary secretory cells].", "content": "1.10(-7)--1.10(-5) g/ml of isadrine induced a 2-phase hyperpolarization changes of MP of the secretory cell. Propranolol (1.10(-6) g/ml) decreased the amplitude of hyperpolarization response of the MP to oxytocin by 36%; 1.10(-9)--1.10(-8) g/ml of isadrine induced a 42% and 53% decrease respectively, and 1.10(-7)--1.10(-5) g/ml blocked the response of secretory cells to oxytocin. The data obtained suggest that catecholamines can effect the MP by means of interaction with beta-adrenoreceptors of mammary secretory cells.", "contents": "[Effect of isadrine and propranolol on the membrane potential of mammary secretory cells]. 1.10(-7)--1.10(-5) g/ml of isadrine induced a 2-phase hyperpolarization changes of MP of the secretory cell. Propranolol (1.10(-6) g/ml) decreased the amplitude of hyperpolarization response of the MP to oxytocin by 36%; 1.10(-9)--1.10(-8) g/ml of isadrine induced a 42% and 53% decrease respectively, and 1.10(-7)--1.10(-5) g/ml blocked the response of secretory cells to oxytocin. The data obtained suggest that catecholamines can effect the MP by means of interaction with beta-adrenoreceptors of mammary secretory cells."}
{"id": "PMID:206474", "title": "[Glucocorticoid-induced hypertiglyceridemia: effects of cortisone acetate on triglyceride secretion rates and post-heparin lipolytic activity in rabbits (author's transl)].", "content": "In order to elucidate the mechanisms of glucocorticoid-induced hypertriglyceridemia, 3mg or 10mg/kg of cortisone acetate were administered daily intramuscularly for 8 days to male albino rabbits which were fed 150g/day of a complete commercial diet. Plasma triglyceride (TG), cholesterol (Chol), free fatty acid (FFA), glucose, IRI, very low density lipoprotein (VLDL)-TG, and post-heparin lipolytic activity (PHLA) were determined. PHLA was measured 10 minutes after a heparin (Novo Co., Denmark; 10 units/kg) injection, and then 30, 60, 120 and 180 minutes after pulse injections of heparin (100 units/kg) at 30 minute intervals up to 120 minutes. In another experiment, following 1 week of daily intramuscular injections of 3mg/kg of cortisone acetate, triglyceride secretion rates (TGSR) were estimated, using intravenous injections of Triton WR-1339 (750mg/kg). Also, plasma glucose, IRI, and FFA responses were measured after an intravenous glucose administration test (1.Og/kg) which was performed before and after cortisone acetate treatment. The results were the following: (1) Significant increase (p less than 0.001) in plasma TG and VLDL-TG without any rise of plasma Chol. (2) Increased plasma IRI, glucose and FFA levels at fasting and after intravenous glucose load. (3) No change in PHLA. (4) Highly significant increments (p less than 0.001) in TGSR. Plasma TG and VLDL-TG showed a significant correlation with fasting plasma IRI and sigma glucose (summation of each time glucose level in intravenous glucose load). These findings suggest that glucocorticoid-induced hypertiglyceridemia is primarily a consequence of increased hepatic TG production rates, through elevated plasma FFA, IRI and glucose levels.", "contents": "[Glucocorticoid-induced hypertiglyceridemia: effects of cortisone acetate on triglyceride secretion rates and post-heparin lipolytic activity in rabbits (author's transl)]. In order to elucidate the mechanisms of glucocorticoid-induced hypertriglyceridemia, 3mg or 10mg/kg of cortisone acetate were administered daily intramuscularly for 8 days to male albino rabbits which were fed 150g/day of a complete commercial diet. Plasma triglyceride (TG), cholesterol (Chol), free fatty acid (FFA), glucose, IRI, very low density lipoprotein (VLDL)-TG, and post-heparin lipolytic activity (PHLA) were determined. PHLA was measured 10 minutes after a heparin (Novo Co., Denmark; 10 units/kg) injection, and then 30, 60, 120 and 180 minutes after pulse injections of heparin (100 units/kg) at 30 minute intervals up to 120 minutes. In another experiment, following 1 week of daily intramuscular injections of 3mg/kg of cortisone acetate, triglyceride secretion rates (TGSR) were estimated, using intravenous injections of Triton WR-1339 (750mg/kg). Also, plasma glucose, IRI, and FFA responses were measured after an intravenous glucose administration test (1.Og/kg) which was performed before and after cortisone acetate treatment. The results were the following: (1) Significant increase (p less than 0.001) in plasma TG and VLDL-TG without any rise of plasma Chol. (2) Increased plasma IRI, glucose and FFA levels at fasting and after intravenous glucose load. (3) No change in PHLA. (4) Highly significant increments (p less than 0.001) in TGSR. Plasma TG and VLDL-TG showed a significant correlation with fasting plasma IRI and sigma glucose (summation of each time glucose level in intravenous glucose load). These findings suggest that glucocorticoid-induced hypertiglyceridemia is primarily a consequence of increased hepatic TG production rates, through elevated plasma FFA, IRI and glucose levels."}
{"id": "PMID:206476", "title": "Crystalloid bodies in Euglena.", "content": "A study has been made of the formation of crystalloid bodies (CB) in the cytoplasm of Euglena gracilis. CB have been found in strains of three bleached mutants as well as in the green wild type where they have been hitherto unknown. These bodies accumulate in the lag-phase of growth in media rich in organic carbon source (ethanol, acetate or sugars). The formation of CB is light-independent and reversible. The ultrastructure of CB reveals that they consist of aggregates of thin plates which are often associated with an osmiophilic substance. Several properties of CB indicate that they do not represent paramylon but are mostly lipid in nature and consist primarily of crystalline wax esters. The formation and role of CB is discussed.", "contents": "Crystalloid bodies in Euglena. A study has been made of the formation of crystalloid bodies (CB) in the cytoplasm of Euglena gracilis. CB have been found in strains of three bleached mutants as well as in the green wild type where they have been hitherto unknown. These bodies accumulate in the lag-phase of growth in media rich in organic carbon source (ethanol, acetate or sugars). The formation of CB is light-independent and reversible. The ultrastructure of CB reveals that they consist of aggregates of thin plates which are often associated with an osmiophilic substance. Several properties of CB indicate that they do not represent paramylon but are mostly lipid in nature and consist primarily of crystalline wax esters. The formation and role of CB is discussed."}
{"id": "PMID:206480", "title": "Epinephrine enhancement of potassium-stimulated immunoreactive insulin secretion. Role of beta-adrenergic receptors.", "content": "Although epinephrine stimulates insulin release by activation of beta-adrenergic receptors, its dominant effect (mediated by stimulation of alpha-adrenergic receptors) is an inhibition of insulin secretion that is powerful enough to suppress the secretory activity of insulin's most potent stimulants. The insulin-secretory response to potassium chloride (KCl) infusion, however, is not suppressed; in fact, in ureter-ligated dogs simultaneously infused with 360 microgram. epinephrine per hour and 2 mEq. KCl per kilogram per hour, insulin release is actually increased about threefold (over controls). Propranolol blockade of beta-adrenergic receptors essentially abolishes the insulin response to KCl infusion, with and without epinephrine. It is unlikely that KCl, like epinephrine, provokes insulin release by direct stimulation of the beta-adrenergic receptors of the beta cells of the pancreatic islets. However, potassium in some way enhances the beta adrenergic (secretory) activity of epinephrine and blunts its usually dominant alpha-adrenergic (inhibitory) effect.", "contents": "Epinephrine enhancement of potassium-stimulated immunoreactive insulin secretion. Role of beta-adrenergic receptors. Although epinephrine stimulates insulin release by activation of beta-adrenergic receptors, its dominant effect (mediated by stimulation of alpha-adrenergic receptors) is an inhibition of insulin secretion that is powerful enough to suppress the secretory activity of insulin's most potent stimulants. The insulin-secretory response to potassium chloride (KCl) infusion, however, is not suppressed; in fact, in ureter-ligated dogs simultaneously infused with 360 microgram. epinephrine per hour and 2 mEq. KCl per kilogram per hour, insulin release is actually increased about threefold (over controls). Propranolol blockade of beta-adrenergic receptors essentially abolishes the insulin response to KCl infusion, with and without epinephrine. It is unlikely that KCl, like epinephrine, provokes insulin release by direct stimulation of the beta-adrenergic receptors of the beta cells of the pancreatic islets. However, potassium in some way enhances the beta adrenergic (secretory) activity of epinephrine and blunts its usually dominant alpha-adrenergic (inhibitory) effect."}
{"id": "PMID:206481", "title": "[125I] Glucagon binding by liver membranes from young and adult rats.", "content": "We have previously shown that adipocytes from adult (between four and five months old) rats have reduced glucagon binding and glucagon-stimulated lipolytic activity when compared with cells from young (1.5 months old) animals. In the present study we measured specific [125I] glucagon binding by purified liver plasma membranes isolated from young and adult rats. When expressed on the basis of membrane protein content, 5'-nucleotidse activity, or specific [125I] insulin binding, the extend of [125I] glucagon binding by liver membranes was not influenced by aging. Furthermore, the degree of [125I] glucagon degradation was the same in both membrane preparations. These data describe a unique condition in which glucagon binding and hormone sensitivity diminish in one tissue but remain unaltered in another.", "contents": "[125I] Glucagon binding by liver membranes from young and adult rats. We have previously shown that adipocytes from adult (between four and five months old) rats have reduced glucagon binding and glucagon-stimulated lipolytic activity when compared with cells from young (1.5 months old) animals. In the present study we measured specific [125I] glucagon binding by purified liver plasma membranes isolated from young and adult rats. When expressed on the basis of membrane protein content, 5'-nucleotidse activity, or specific [125I] insulin binding, the extend of [125I] glucagon binding by liver membranes was not influenced by aging. Furthermore, the degree of [125I] glucagon degradation was the same in both membrane preparations. These data describe a unique condition in which glucagon binding and hormone sensitivity diminish in one tissue but remain unaltered in another."}
{"id": "PMID:206482", "title": "Cholinergic inhibition of adrenergic neurotransmission in the canine gastric artery.", "content": "Experiments were performed to examine the possible interaction between the cholinergic transmitter and the reactivity of gastric arteries to adrenergic activation. Helical strips of dogs' gastric arteries were mounted for isometric tension recording. The strips contracted on exposure to norepinephrine; these contractions were inhibited by phenoxybenzamine. Electrical stimulation caused an increase in tension, which was abolished by tetrodotoxin and phenoxybenzamine, indicating that electrical stimulation causes contraction by liberation of norepinephrine. Acetylcholine did not alter basal tension; it caused relaxation during responses to electrical simulation, but not during those to norepinephrine. The relaxation caused by acetylcholine was abolished by atropine. This indicates that acetylcholine inhibits adrenergic neurotransmission in the dog's gastric artery. When added during electrical stimulation, atropine caused an increase in tension. The same concentrations of atropine did not affect basal tension or the response to norephrine. Physostigmine depressed the response to electrical stimulation, but not that to norepinephrine. In the blood-perfused stomach of the intact dog, vagal stimulation depressed vasoconstrictions caused by sympathetic nerve stimulation more than comparable constrictor responses obtained with the infusion of norepinephrine. These experiments suggest that liberated acetylcholine can modulate adrenergic neurotransmission in the gastric blood vessels. The removal of cholinergic inhibition on the release of norepinephrine may help explain why vagotomy has a beneficial effect on gastric bleeding.", "contents": "Cholinergic inhibition of adrenergic neurotransmission in the canine gastric artery. Experiments were performed to examine the possible interaction between the cholinergic transmitter and the reactivity of gastric arteries to adrenergic activation. Helical strips of dogs' gastric arteries were mounted for isometric tension recording. The strips contracted on exposure to norepinephrine; these contractions were inhibited by phenoxybenzamine. Electrical stimulation caused an increase in tension, which was abolished by tetrodotoxin and phenoxybenzamine, indicating that electrical stimulation causes contraction by liberation of norepinephrine. Acetylcholine did not alter basal tension; it caused relaxation during responses to electrical simulation, but not during those to norepinephrine. The relaxation caused by acetylcholine was abolished by atropine. This indicates that acetylcholine inhibits adrenergic neurotransmission in the dog's gastric artery. When added during electrical stimulation, atropine caused an increase in tension. The same concentrations of atropine did not affect basal tension or the response to norephrine. Physostigmine depressed the response to electrical stimulation, but not that to norepinephrine. In the blood-perfused stomach of the intact dog, vagal stimulation depressed vasoconstrictions caused by sympathetic nerve stimulation more than comparable constrictor responses obtained with the infusion of norepinephrine. These experiments suggest that liberated acetylcholine can modulate adrenergic neurotransmission in the gastric blood vessels. The removal of cholinergic inhibition on the release of norepinephrine may help explain why vagotomy has a beneficial effect on gastric bleeding."}
{"id": "PMID:206483", "title": "Effect of exchange exocrine pancreatic insufficiency on small intestine in the mouse.", "content": "A genetically conditioned mouse model of exocrine pancreatic insufficiency (epi) has been used to study the effect of the absence of lumenal proteases on small intestinal mucosal proteins. The small bowel was divided into eight equal segments. Enzyme activity was increased only in the first three segments in the case of maltase, sucrase, and lactase (all mol wt above 200,000). Alkaline phosphatase (mol wt 145,000), trehalase (mol wt 95,000), and peptidase (mol wt 175,000) activities were unaffected in proximal segments from epi mice. Proximal brush border proteins were identified and measured quantitatively by sodium dodecyl sulfate acrylamide gel electrophoresis. Those enzymes with increased activity were associated with increased amounts of protein in epi mice. Double labeled studies of protein turnover revealed a longer half-life for large brush border proteins (mol wt above 175,000) in epi mice than in normal mice. Enterokinase activity (a marker for duodenal mucosa) was nearly absent from the duodenum of epi mice. Receptors for the intrinsic factor-vitamin B12 complex (markers for ileal mucosal) were present in the ileum equally in normal and in epi mice. Enterokinase activity can be induced in epi mice by feeding its substrate trypsinogen, but not by trypsin or chymotrypsinogen. Epi mice thus retain the ability to synthesize enterokinase. Pancreatic proteases play an important role in the turnover of certain large mucosal proteins and in the induction of enterokinase.", "contents": "Effect of exchange exocrine pancreatic insufficiency on small intestine in the mouse. A genetically conditioned mouse model of exocrine pancreatic insufficiency (epi) has been used to study the effect of the absence of lumenal proteases on small intestinal mucosal proteins. The small bowel was divided into eight equal segments. Enzyme activity was increased only in the first three segments in the case of maltase, sucrase, and lactase (all mol wt above 200,000). Alkaline phosphatase (mol wt 145,000), trehalase (mol wt 95,000), and peptidase (mol wt 175,000) activities were unaffected in proximal segments from epi mice. Proximal brush border proteins were identified and measured quantitatively by sodium dodecyl sulfate acrylamide gel electrophoresis. Those enzymes with increased activity were associated with increased amounts of protein in epi mice. Double labeled studies of protein turnover revealed a longer half-life for large brush border proteins (mol wt above 175,000) in epi mice than in normal mice. Enterokinase activity (a marker for duodenal mucosa) was nearly absent from the duodenum of epi mice. Receptors for the intrinsic factor-vitamin B12 complex (markers for ileal mucosal) were present in the ileum equally in normal and in epi mice. Enterokinase activity can be induced in epi mice by feeding its substrate trypsinogen, but not by trypsin or chymotrypsinogen. Epi mice thus retain the ability to synthesize enterokinase. Pancreatic proteases play an important role in the turnover of certain large mucosal proteins and in the induction of enterokinase."}
{"id": "PMID:206486", "title": "A chromosomal translocation causing overproduction of iso-2-cytochrome c in yeast.", "content": "The CYC7-1 mutation in the yeast Saccharomyces cerevisiae causes the production of approximately 30 times the normal amount of iso-2-cytochrome c. Genetic analysis established that the CYC7-1 mutation is a reciprocal translocation involving the left arm of chromosome V and the right arm of chromosome XVI. The chromosome V arm was broken adjacent to the gene CYC7, which determines the primary structure of iso-2-cytochrome c, and this fragment containing the CYC7 gene was joined to the segment of chromosome XVI. It appears as though the elevation of iso-2-cytochrome c is caused by an abnormal controlling region adjacent to the structural region of the CYC7 gene.", "contents": "A chromosomal translocation causing overproduction of iso-2-cytochrome c in yeast. The CYC7-1 mutation in the yeast Saccharomyces cerevisiae causes the production of approximately 30 times the normal amount of iso-2-cytochrome c. Genetic analysis established that the CYC7-1 mutation is a reciprocal translocation involving the left arm of chromosome V and the right arm of chromosome XVI. The chromosome V arm was broken adjacent to the gene CYC7, which determines the primary structure of iso-2-cytochrome c, and this fragment containing the CYC7 gene was joined to the segment of chromosome XVI. It appears as though the elevation of iso-2-cytochrome c is caused by an abnormal controlling region adjacent to the structural region of the CYC7 gene."}
{"id": "PMID:206487", "title": "[Inheritance characteristics of syndactylia].", "content": "On the basis of the analysis of 39 pedigrees with syndactylies it is concluded an autosomal dominant mode of the inheritance with incomplete penetrance. The variability of penetrance is more pronounced in females who are frequently healthy carriers of the gene transmitting it to both sexes. The significant prevalence of males in syndactylies can be explained by deathes of female embryos in utero, the sex ratio in healthy sibses being normal.", "contents": "[Inheritance characteristics of syndactylia]. On the basis of the analysis of 39 pedigrees with syndactylies it is concluded an autosomal dominant mode of the inheritance with incomplete penetrance. The variability of penetrance is more pronounced in females who are frequently healthy carriers of the gene transmitting it to both sexes. The significant prevalence of males in syndactylies can be explained by deathes of female embryos in utero, the sex ratio in healthy sibses being normal."}
{"id": "PMID:206489", "title": "Abnormal vitamin D metabolism in cirrhosis.", "content": "Vitamin D metabolism was investigated in 10 patients with cirrhosis. Mean plasma 25 hydroxycholecalciferol (25 OHD) centration in alcoholic cirrhosis was lower than in controls but the difference was not significant. In three patients restudied after the summer, plasma 25 OHD had risen. In contrast to the finding in normal subjects, the half-life of intravenously administered 3H cholecalciferol was short in cirrhotics and showed no correlation with plasma 25 OHD. Furthermore, the appearance of 3H 25 OHD from 3H cholecalciferol was reduced compared to the control group four hours after injection. Increased rate of metabolism of cholecalciferol and deficient production of 25 ohd contribute to vitamin D deficiency in liver disease.", "contents": "Abnormal vitamin D metabolism in cirrhosis. Vitamin D metabolism was investigated in 10 patients with cirrhosis. Mean plasma 25 hydroxycholecalciferol (25 OHD) centration in alcoholic cirrhosis was lower than in controls but the difference was not significant. In three patients restudied after the summer, plasma 25 OHD had risen. In contrast to the finding in normal subjects, the half-life of intravenously administered 3H cholecalciferol was short in cirrhotics and showed no correlation with plasma 25 OHD. Furthermore, the appearance of 3H 25 OHD from 3H cholecalciferol was reduced compared to the control group four hours after injection. Increased rate of metabolism of cholecalciferol and deficient production of 25 ohd contribute to vitamin D deficiency in liver disease."}
{"id": "PMID:206491", "title": "[The diagnosis and therapy of bilateral Wilm's tumour (author's transl)].", "content": "The diagnosis and successful treatment in two patients with bilateral Wilms' tumour are described. In one patient the kidneys were affected simultaneously, the left kidney being duplex; in the second patient, the tumours occurred sequentially.", "contents": "[The diagnosis and therapy of bilateral Wilm's tumour (author's transl)]. The diagnosis and successful treatment in two patients with bilateral Wilms' tumour are described. In one patient the kidneys were affected simultaneously, the left kidney being duplex; in the second patient, the tumours occurred sequentially."}
{"id": "PMID:206492", "title": "[Organic complications of alcoholism].", "content": "With the enormous increase of alcohol consumption after a period of latency of many years an increase of organic damage is associated, the knowledge of which leads to correct diagnosis. Most often the liver, the central organ of alcohol decomposition, is affected. Many other organs are involved in a specific way. Symptomatology and diagnosis are dealt with in detail.", "contents": "[Organic complications of alcoholism]. With the enormous increase of alcohol consumption after a period of latency of many years an increase of organic damage is associated, the knowledge of which leads to correct diagnosis. Most often the liver, the central organ of alcohol decomposition, is affected. Many other organs are involved in a specific way. Symptomatology and diagnosis are dealt with in detail."}
{"id": "PMID:206496", "title": "Effect of somatostatin in the Syrian hamster bearing a transplantable islet-cell tumor.", "content": "The influence of somatostatin (SRIF) on blood glucose, plasma insulin and plasma glucagon was studied in hamsters bearing a transplantable islet-cell tumor secreting insulin and glucagon as well as in normal controls. Fed anesthetized animals were infused intraperitoneally either at a dose of 10 microgram in 15 min or of 150 microgram in 30 min, and intravenously at a dose of 250 microgram in 30 min. Blood was withdrawn from the jugular vein before and after infusion. Before the infusions, tumor bearing animals (TB) had lower blood glucose, markedly elevated plasma glucagon and slightly lower plasma insulin by comparison with normal hamsters (N). Both doses of somatostatin infused by the intraperitoneal route produced a slight but significant hypoglycemia in TB hamsters but not in normals. Ten microgram SRIF did not affect insulin and plasma glucagon levels whereas 150 microgram SRIF significantly depressed plasma insulin in both types of hamsters (N and TB). This latter dose of SRIF decreased plasma glucagon in normal but not in tumor-bearing hamsters. Intravenous infusion of 250 microgram SRIF did not reduce the hyperglucagonemia of TB hamsters either. These results indicate that somatostatin does not reduce the hyperglucagonemia due to the transplantable islet-cell tumor but nevertheless decreases blood glucose and plasma insulin.", "contents": "Effect of somatostatin in the Syrian hamster bearing a transplantable islet-cell tumor. The influence of somatostatin (SRIF) on blood glucose, plasma insulin and plasma glucagon was studied in hamsters bearing a transplantable islet-cell tumor secreting insulin and glucagon as well as in normal controls. Fed anesthetized animals were infused intraperitoneally either at a dose of 10 microgram in 15 min or of 150 microgram in 30 min, and intravenously at a dose of 250 microgram in 30 min. Blood was withdrawn from the jugular vein before and after infusion. Before the infusions, tumor bearing animals (TB) had lower blood glucose, markedly elevated plasma glucagon and slightly lower plasma insulin by comparison with normal hamsters (N). Both doses of somatostatin infused by the intraperitoneal route produced a slight but significant hypoglycemia in TB hamsters but not in normals. Ten microgram SRIF did not affect insulin and plasma glucagon levels whereas 150 microgram SRIF significantly depressed plasma insulin in both types of hamsters (N and TB). This latter dose of SRIF decreased plasma glucagon in normal but not in tumor-bearing hamsters. Intravenous infusion of 250 microgram SRIF did not reduce the hyperglucagonemia of TB hamsters either. These results indicate that somatostatin does not reduce the hyperglucagonemia due to the transplantable islet-cell tumor but nevertheless decreases blood glucose and plasma insulin."}
{"id": "PMID:206497", "title": "Calcium antagonists and lipolysis in isolated rat epididymal adipocytes: effects of tetracaine, manganese, cobaltous and lanthanum ions and D600.", "content": "The present study reports the effects on lipolysis occurring in isolated rat epididymal adipocytes of several agents which have each been found to interfere with membrane calcium transport in a variety of tissues. As reported by other workers, the local tetracaine was a strong inhibitor of hormone accelerated but not of basal lipolysis. The bivalent cations Mn2+ and Co2+ were similarly found to inhibit lipolysis stimulated with either epinephrine, ACTH, theophylline or dibutyryl cyclic AMP, whereas basal lipolysis was not markedly altered. This effect of Mn2+ and Co2+ was not mimicked by either Sr2+, Ba2+, Mg2+ or Ca2+. Cyclic AMP levels in adipocytes stimulated with epinephrine or ACTH tended to be higher in the presence of Mn2+ and Co2+. It is concluded, therefore, that Mn2+ and Co2+ inhibit lipolysis by uncoupling cyclic AMP accumulation from activation of triglyceride lipase. In contrast to Mn2+ and Co2+, the calcium antagonists La3+ and D600 were without effect on lipolysis. The antilipolytic effect of tetracaine, Mn2+ and Co2+ was found to persist in the absence of extracellular calcium, suggesting therefore that the antilipolytic effect of these drugs is unrelated to inhibition of calcium influx into adipocytes. The possibility is discussed that lipolytic agents cause an intracellular redistribution of calcium ion and that local anesthetics, Mn2+ and Co2+ interfere with lipolysis by preventing this intracellular redistribution of calcium.", "contents": "Calcium antagonists and lipolysis in isolated rat epididymal adipocytes: effects of tetracaine, manganese, cobaltous and lanthanum ions and D600. The present study reports the effects on lipolysis occurring in isolated rat epididymal adipocytes of several agents which have each been found to interfere with membrane calcium transport in a variety of tissues. As reported by other workers, the local tetracaine was a strong inhibitor of hormone accelerated but not of basal lipolysis. The bivalent cations Mn2+ and Co2+ were similarly found to inhibit lipolysis stimulated with either epinephrine, ACTH, theophylline or dibutyryl cyclic AMP, whereas basal lipolysis was not markedly altered. This effect of Mn2+ and Co2+ was not mimicked by either Sr2+, Ba2+, Mg2+ or Ca2+. Cyclic AMP levels in adipocytes stimulated with epinephrine or ACTH tended to be higher in the presence of Mn2+ and Co2+. It is concluded, therefore, that Mn2+ and Co2+ inhibit lipolysis by uncoupling cyclic AMP accumulation from activation of triglyceride lipase. In contrast to Mn2+ and Co2+, the calcium antagonists La3+ and D600 were without effect on lipolysis. The antilipolytic effect of tetracaine, Mn2+ and Co2+ was found to persist in the absence of extracellular calcium, suggesting therefore that the antilipolytic effect of these drugs is unrelated to inhibition of calcium influx into adipocytes. The possibility is discussed that lipolytic agents cause an intracellular redistribution of calcium ion and that local anesthetics, Mn2+ and Co2+ interfere with lipolysis by preventing this intracellular redistribution of calcium."}
{"id": "PMID:206498", "title": "Regulation of pyruvate dehydrogenase by Ca2+, 3'5' cyclic AMP and adrenalin in isolated rat kidney tubules.", "content": "Renal pyruvate dehydrogenasea activity was measured in suspensions of kidney cortex tubules from fed rats after incubation with various concentrations of Ca2+, 3'5' cyclic AMP or adrenalin. At certain concentrations these agents all decreased pyruvate dehydrogenasea activity and increased glucose formation from pyruvate. There appeared to be some interdependence between the effects of Ca2+ and 3,5, cyclic AMP on pyruvate dehydrogenasea activity. Effects of adrenalin on pyruvate dehydrogenasea activity were no longer observed when palmitate was included in incubations. The possibility that regulation of pyruvate dehydrogenasea may indirectly contribute to the control of gluconeogenesis by influencing pyruvate metabolism is briefly discussed.", "contents": "Regulation of pyruvate dehydrogenase by Ca2+, 3'5' cyclic AMP and adrenalin in isolated rat kidney tubules. Renal pyruvate dehydrogenasea activity was measured in suspensions of kidney cortex tubules from fed rats after incubation with various concentrations of Ca2+, 3'5' cyclic AMP or adrenalin. At certain concentrations these agents all decreased pyruvate dehydrogenasea activity and increased glucose formation from pyruvate. There appeared to be some interdependence between the effects of Ca2+ and 3,5, cyclic AMP on pyruvate dehydrogenasea activity. Effects of adrenalin on pyruvate dehydrogenasea activity were no longer observed when palmitate was included in incubations. The possibility that regulation of pyruvate dehydrogenasea may indirectly contribute to the control of gluconeogenesis by influencing pyruvate metabolism is briefly discussed."}
{"id": "PMID:206499", "title": "Postmaturity in the rat: phosphorylase, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the fetal liver.", "content": "Liver glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were increased in the postmature rat fetus (23.5 day old) when compared to term rat fetus (21.5 day old). Postmaturity was without effect on liver phosphorylase activity. The three liver enzyme activities were also determined in normal 2 day old neonates. These results are correlated with the mobilisation of fetal liver glycogen occuring during postmaturity in the rat and are discussed in relation to the secretory pattern of the pancreatic hormones.", "contents": "Postmaturity in the rat: phosphorylase, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the fetal liver. Liver glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were increased in the postmature rat fetus (23.5 day old) when compared to term rat fetus (21.5 day old). Postmaturity was without effect on liver phosphorylase activity. The three liver enzyme activities were also determined in normal 2 day old neonates. These results are correlated with the mobilisation of fetal liver glycogen occuring during postmaturity in the rat and are discussed in relation to the secretory pattern of the pancreatic hormones."}
{"id": "PMID:206500", "title": "Dynamics of hormone release from the perfused canine thyroid during cyclic AMP infusion.", "content": "In order to try to characterize the sequence of processes leading to hormone secretion from the stimulated thyroid, the effect of cyclic 3'5' adenosine monophosphate (cAMP) and related compounds were examined in 15 two-sided perfusions of canine thyroids isolated in situ. T4 and T3 concentrations in the effluent were measured radioimmunologically. cAMP 5 mM and TSH 100 muU per ml induced the same pattern of hormone release from the thyroid. After a latency period of 15--25 minutes a steep increase occurred in both T4 and T3 release. During the initial part of the stimulation the rise in T4 relase was somewhat slower than that of T3 release. The prolonged latency period before response earlier recorded in the same preparation during infusions of low concentrations of TSH was not observed during infusions of decreasing concentrations of cAMP (1, 0.8, 0.5 and 0.2 mM) or theophylline (5 and 1 mM). Either there was no response or the latency period was of the same length as that observed after a strong stimulus. These findings suggest that the latency period can be divided in two parts: () a variable, dose dependent satency period confined to the early part of the process sequence leading to secretion--i.e. before cAMP exerts its effect, and 2) an obligatory latency period related to the processes taking place after the formation of pseudopods. The duration of these late processes seems to be independent of the degree of stimulation.", "contents": "Dynamics of hormone release from the perfused canine thyroid during cyclic AMP infusion. In order to try to characterize the sequence of processes leading to hormone secretion from the stimulated thyroid, the effect of cyclic 3'5' adenosine monophosphate (cAMP) and related compounds were examined in 15 two-sided perfusions of canine thyroids isolated in situ. T4 and T3 concentrations in the effluent were measured radioimmunologically. cAMP 5 mM and TSH 100 muU per ml induced the same pattern of hormone release from the thyroid. After a latency period of 15--25 minutes a steep increase occurred in both T4 and T3 release. During the initial part of the stimulation the rise in T4 relase was somewhat slower than that of T3 release. The prolonged latency period before response earlier recorded in the same preparation during infusions of low concentrations of TSH was not observed during infusions of decreasing concentrations of cAMP (1, 0.8, 0.5 and 0.2 mM) or theophylline (5 and 1 mM). Either there was no response or the latency period was of the same length as that observed after a strong stimulus. These findings suggest that the latency period can be divided in two parts: () a variable, dose dependent satency period confined to the early part of the process sequence leading to secretion--i.e. before cAMP exerts its effect, and 2) an obligatory latency period related to the processes taking place after the formation of pseudopods. The duration of these late processes seems to be independent of the degree of stimulation."}
{"id": "PMID:206501", "title": "Effect of parathyroid extract on renal cyclic AMP excretion in patients with normocalciuric nephrolithiasis.", "content": "It is uncertain whether normocalcemic, normocalciuric patients with calcium nephrolithiasis have a disorder of calcium metabolism. We studied the effect of a parathyroid extract (PTE) INFUSION (1.4 U/kg body weight) on the urinary cyclic AMP excretion in 16 such patients. For comparison, we investigated groups of normal individuals and patients with primary hyperparathyroidism, renal insufficiency and different gastrointestinal diseases. The increase of cyclic AMP above basal excretion in patients with nephrolithiasis was only 1.2 +/- 0.3 mumol/h (mean +/- SEM), versus 2.5 +/- 0.5 mumol/h in normal subjects (p less than 0.05) although the basal excretion was similar. Patients with renal insufficiency had low basal excretion of cyclic AMP and little stimulation of excretion by PTH (increase, 0.3 +/- 0.06 mumol). Patients with primary hyperparathyroidism had high baseline cyclic AMP excretion but sub-normal stimulation by PTE (increase, 0.46 +/- 0.13); in contrast, patients with different gastrointestinal disease had high baseline excretion and supranormal stimulation of cyclic AMP excretion (increase, 5.2 +/- 0.6). We speculate that an impaired response to PTH might be involved in the slightly increased urinary calcium excretion in normocalcemic stone formers suggested by others.", "contents": "Effect of parathyroid extract on renal cyclic AMP excretion in patients with normocalciuric nephrolithiasis. It is uncertain whether normocalcemic, normocalciuric patients with calcium nephrolithiasis have a disorder of calcium metabolism. We studied the effect of a parathyroid extract (PTE) INFUSION (1.4 U/kg body weight) on the urinary cyclic AMP excretion in 16 such patients. For comparison, we investigated groups of normal individuals and patients with primary hyperparathyroidism, renal insufficiency and different gastrointestinal diseases. The increase of cyclic AMP above basal excretion in patients with nephrolithiasis was only 1.2 +/- 0.3 mumol/h (mean +/- SEM), versus 2.5 +/- 0.5 mumol/h in normal subjects (p less than 0.05) although the basal excretion was similar. Patients with renal insufficiency had low basal excretion of cyclic AMP and little stimulation of excretion by PTH (increase, 0.3 +/- 0.06 mumol). Patients with primary hyperparathyroidism had high baseline cyclic AMP excretion but sub-normal stimulation by PTE (increase, 0.46 +/- 0.13); in contrast, patients with different gastrointestinal disease had high baseline excretion and supranormal stimulation of cyclic AMP excretion (increase, 5.2 +/- 0.6). We speculate that an impaired response to PTH might be involved in the slightly increased urinary calcium excretion in normocalcemic stone formers suggested by others."}
{"id": "PMID:206502", "title": "An estimation of the parathyroid hormone secretion rate in vitamin D deficient rats.", "content": "In an attempt to define the rate of endogenous secretion of parathyroid hormone in vitamin D deficiency, graded amounts of hormone were infused constantly into vitamin D deficient and vitamin D fed acutely thyroparathyroidectomized rats in a perfusion balance study. The dose of hormone needed to compensate for acute thyroparathyroidectomy was estimated. Serum levels of calcium and phosphorus, renal clearances of phosphorus and urinary excretion of cyclic AMP, each determined 16 hr after the surgery, were employed as parameters of the hormone effect. It was concluded that, in the condition of the perfusion balance study, the secretion rate of parathyroid hormone was 5.1-8.6 USP u/hr in the vitamin D deficient animals compared with 0.81-0.84 USP u/hr in the control.", "contents": "An estimation of the parathyroid hormone secretion rate in vitamin D deficient rats. In an attempt to define the rate of endogenous secretion of parathyroid hormone in vitamin D deficiency, graded amounts of hormone were infused constantly into vitamin D deficient and vitamin D fed acutely thyroparathyroidectomized rats in a perfusion balance study. The dose of hormone needed to compensate for acute thyroparathyroidectomy was estimated. Serum levels of calcium and phosphorus, renal clearances of phosphorus and urinary excretion of cyclic AMP, each determined 16 hr after the surgery, were employed as parameters of the hormone effect. It was concluded that, in the condition of the perfusion balance study, the secretion rate of parathyroid hormone was 5.1-8.6 USP u/hr in the vitamin D deficient animals compared with 0.81-0.84 USP u/hr in the control."}
{"id": "PMID:206506", "title": "Improving continuity of care through a state hospital-CMHC liaison program.", "content": "After several abortive attempts, a state hospital and a community mental health center located in the same county made a more successful attempt to improve continuity of care. A study of 78 discharged hospital patients identified several problems in the continuity-of-care system. A liaison team made up of a social worker from the hospital and a psychiatric nurse from the center was set up to carry out such tasks as contacting county residents admitted to the hospital, participating in treatment and discharge planning, and contacting patients who did not keep aftercare appointments. The program had several positive results; the authors believe they were related to such factors as an objective definition of the problems, administrative cooperation, and strong linkage, through a middle-management team, between the liaison team and top-level management and between the hospital and the center.", "contents": "Improving continuity of care through a state hospital-CMHC liaison program. After several abortive attempts, a state hospital and a community mental health center located in the same county made a more successful attempt to improve continuity of care. A study of 78 discharged hospital patients identified several problems in the continuity-of-care system. A liaison team made up of a social worker from the hospital and a psychiatric nurse from the center was set up to carry out such tasks as contacting county residents admitted to the hospital, participating in treatment and discharge planning, and contacting patients who did not keep aftercare appointments. The program had several positive results; the authors believe they were related to such factors as an objective definition of the problems, administrative cooperation, and strong linkage, through a middle-management team, between the liaison team and top-level management and between the hospital and the center."}
{"id": "PMID:206508", "title": "No association of red cell adenylate kinase phenotypes with affective disorders.", "content": "Red cell adenylate kinase (AK) phenotypes were studies in 195 patients with affective disorders (41 with the bipolar and 81 with the unipolar form of the disease) and 418 controls. No significant differences were found between patients and controls and between patients with different types of affective disorders. Thus the previous observation by Rundle et al. (1977) showing an increased frequency of the AK2 allele in the unipolar group was not confirmed.", "contents": "No association of red cell adenylate kinase phenotypes with affective disorders. Red cell adenylate kinase (AK) phenotypes were studies in 195 patients with affective disorders (41 with the bipolar and 81 with the unipolar form of the disease) and 418 controls. No significant differences were found between patients and controls and between patients with different types of affective disorders. Thus the previous observation by Rundle et al. (1977) showing an increased frequency of the AK2 allele in the unipolar group was not confirmed."}
{"id": "PMID:206509", "title": "Hereditary sensory neuropathy, a new type.", "content": "Two brothers with a new type of hereditary sensory neuropathy are described. The main clinical feature is late onset sensory ataxia without ulcerating acropathy or other autonomic abnormality. The older patient also has oculomotor dysfunction and extensor plantar responses.", "contents": "Hereditary sensory neuropathy, a new type. Two brothers with a new type of hereditary sensory neuropathy are described. The main clinical feature is late onset sensory ataxia without ulcerating acropathy or other autonomic abnormality. The older patient also has oculomotor dysfunction and extensor plantar responses."}
{"id": "PMID:206510", "title": "Regional mapping on human genes for phosphoglucomutase-1 on chromosome 1 and beta-glucuronidase on chromosome 7 using mouse x human hybrids.", "content": "Two independent mouse-human somatic cell hybrid clones contained different, de novo chromosome rearrangements involving the short arm of human chromosome 1. One hybrid clone contained a translocation between human chromosomes 1 and 7; the other clone contained a rearrangement product between human chromosomes 1 and 14. Analysis of these clones for expression of genes previously assigned to chromosome 7 and to the short arm of chromosome 1 provided evidence for localization of PGM--1 in segment 1p22.1 leads to 1p31.1, AK--2, ENO--1 and UMPK in region 1pter leads to 1p31.1, and GUS in region 7 pter leads to 7q22. The results have been used to examine the relationship between cytologic and genetic map distances on the short arm of chromosome 1.", "contents": "Regional mapping on human genes for phosphoglucomutase-1 on chromosome 1 and beta-glucuronidase on chromosome 7 using mouse x human hybrids. Two independent mouse-human somatic cell hybrid clones contained different, de novo chromosome rearrangements involving the short arm of human chromosome 1. One hybrid clone contained a translocation between human chromosomes 1 and 7; the other clone contained a rearrangement product between human chromosomes 1 and 14. Analysis of these clones for expression of genes previously assigned to chromosome 7 and to the short arm of chromosome 1 provided evidence for localization of PGM--1 in segment 1p22.1 leads to 1p31.1, AK--2, ENO--1 and UMPK in region 1pter leads to 1p31.1, and GUS in region 7 pter leads to 7q22. The results have been used to examine the relationship between cytologic and genetic map distances on the short arm of chromosome 1."}
{"id": "PMID:206514", "title": "The seroepidemiological pattern of acute viral hepatitis. An epidemiological study on viral hepatitis in the Hannover region.", "content": "The natural incidence of the etiologically distinct types of viral hepatitis was determined by investigating acute phase sera of symptomatic hepatitis cases occuring in the Hannover area in 1975 for the presence of hepatitis B surface antigen, antibodies to hepatitis A, hepatitis B core and surface antigens, and by measuring the IgM serum levels. Fourteen different seroepidemiologic patterns were recognized. Although there was a high prevalence of hepatitis A antibody in the population, the frequency of hepatitis A was low (n = 56) suggesting that the hepatitis A virus does not play a major role in symptomatic hepatitis in the Hannover area at present. Spread of the hepatitis A virus was mostly associated with person-to-person contact or tourist travel in southern Europe. Hepatitis B was the predominant type of hepatitis (n = 211). Hepatitis non-A, non-B was observed infrequently (n = 62). A high percentage of patients with hepatitis B and hepatitis non-A, non-B reported parenteral exposure to potentially contaminated materials. No other findings, however, suggested an infectious etiology of hepatitis non-A, non-B.", "contents": "The seroepidemiological pattern of acute viral hepatitis. An epidemiological study on viral hepatitis in the Hannover region. The natural incidence of the etiologically distinct types of viral hepatitis was determined by investigating acute phase sera of symptomatic hepatitis cases occuring in the Hannover area in 1975 for the presence of hepatitis B surface antigen, antibodies to hepatitis A, hepatitis B core and surface antigens, and by measuring the IgM serum levels. Fourteen different seroepidemiologic patterns were recognized. Although there was a high prevalence of hepatitis A antibody in the population, the frequency of hepatitis A was low (n = 56) suggesting that the hepatitis A virus does not play a major role in symptomatic hepatitis in the Hannover area at present. Spread of the hepatitis A virus was mostly associated with person-to-person contact or tourist travel in southern Europe. Hepatitis B was the predominant type of hepatitis (n = 211). Hepatitis non-A, non-B was observed infrequently (n = 62). A high percentage of patients with hepatitis B and hepatitis non-A, non-B reported parenteral exposure to potentially contaminated materials. No other findings, however, suggested an infectious etiology of hepatitis non-A, non-B."}
{"id": "PMID:206515", "title": "Diarrhea in newborn cynomologus monkeys infected with human rotavirus.", "content": "Of six newborn cynomolgus monkeys (Macaca fascicularis) naturally delivered and normally nursed five developed diarrhea after oral administration of human rotavirus. Virus excretion was observed in the stool of four animals. This virus was transmitted to four out of six other monkeys causing diarrhea in only one animal.", "contents": "Diarrhea in newborn cynomologus monkeys infected with human rotavirus. Of six newborn cynomolgus monkeys (Macaca fascicularis) naturally delivered and normally nursed five developed diarrhea after oral administration of human rotavirus. Virus excretion was observed in the stool of four animals. This virus was transmitted to four out of six other monkeys causing diarrhea in only one animal."}
{"id": "PMID:206516", "title": "Specificity studies of leukocytic catecholamine receptors.", "content": "Using tritium-labeled dl(+/-)epinephrine, we have extended previous studies demonstrating binding of epinephrine to human leukocytes. We have now further assessed the biological significance of this catecholamine binding by comparing the specificity of binding by human leukocytes with the ability of these compounds to inhibit epinephrine-stimulated adenyl cyclase. Binding is specific for catechols, but does not distinguish between physiologically active and inactive stereo isomers, nor between alpha- and beta-adrenergic agonists. Although 2.5 X 10(-4) M 1(-)DOPA, dopamine, d(+)epinephrine and serotonin failed to stimulate leukocytic adenyl cyclase and prevented adenyl cyclase stimulation by 2.5 X 10(-4) M 1(-)epinephrine, the inhibition of adenyl cyclase by d(+)epinephrine is noncompetitive. This catechol-binding site is clearly not the beta-adrenergic receptor. Its physiological significance, if any, remains to be elucidated.", "contents": "Specificity studies of leukocytic catecholamine receptors. Using tritium-labeled dl(+/-)epinephrine, we have extended previous studies demonstrating binding of epinephrine to human leukocytes. We have now further assessed the biological significance of this catecholamine binding by comparing the specificity of binding by human leukocytes with the ability of these compounds to inhibit epinephrine-stimulated adenyl cyclase. Binding is specific for catechols, but does not distinguish between physiologically active and inactive stereo isomers, nor between alpha- and beta-adrenergic agonists. Although 2.5 X 10(-4) M 1(-)DOPA, dopamine, d(+)epinephrine and serotonin failed to stimulate leukocytic adenyl cyclase and prevented adenyl cyclase stimulation by 2.5 X 10(-4) M 1(-)epinephrine, the inhibition of adenyl cyclase by d(+)epinephrine is noncompetitive. This catechol-binding site is clearly not the beta-adrenergic receptor. Its physiological significance, if any, remains to be elucidated."}
{"id": "PMID:206517", "title": "Adenyl cyclase.", "content": "Certain hormones regulate the activity of their target cells by stimulating adenyl cyclase, which is an enzyme located within the target cell's plasma membrane. Adenyl cyclase catalyzes the formation of cyclic AMP, which is released into the cell and modulates cell functions. In this communication the characteristics of adenyl cyclase are reviewed. The coupling between hormone receptors and this enzyme is discussed as is the ability of agents such as hormones, ATP, magnesium, calcium, guanine nucleotides and prostaglandins to alter cyclase activity. Several diseases that result from derangements of the adenyl cyclase system are known and the molecular bases for these diseases are discussed in this review.", "contents": "Adenyl cyclase. Certain hormones regulate the activity of their target cells by stimulating adenyl cyclase, which is an enzyme located within the target cell's plasma membrane. Adenyl cyclase catalyzes the formation of cyclic AMP, which is released into the cell and modulates cell functions. In this communication the characteristics of adenyl cyclase are reviewed. The coupling between hormone receptors and this enzyme is discussed as is the ability of agents such as hormones, ATP, magnesium, calcium, guanine nucleotides and prostaglandins to alter cyclase activity. Several diseases that result from derangements of the adenyl cyclase system are known and the molecular bases for these diseases are discussed in this review."}
{"id": "PMID:206518", "title": "Cyclic AMP.", "content": "Cyclic AMP mediates the effects of many hormones on their target cells. Some of the mechanisms by which this occurs are discussed in this review. The role of cyclic AMP in regulating glycogen metabolism in liver and skeletal muscle is firmly established. Data suggesting that cyclic AMP mediates hormonally stimulated salivary gland amylase secretion, cardiac muscle contractility, smooth muscle relaxation, and platelet aggregation are summarized.", "contents": "Cyclic AMP. Cyclic AMP mediates the effects of many hormones on their target cells. Some of the mechanisms by which this occurs are discussed in this review. The role of cyclic AMP in regulating glycogen metabolism in liver and skeletal muscle is firmly established. Data suggesting that cyclic AMP mediates hormonally stimulated salivary gland amylase secretion, cardiac muscle contractility, smooth muscle relaxation, and platelet aggregation are summarized."}
{"id": "PMID:206519", "title": "Chains of alternating sulfur and pi-bonded atoms in eight small proteins.", "content": "This paper demonstrates the existence of regions in eight small globular proteins in which the side chains of sulfur-containing amino acids (cysteine and methionine) alternate in space with side chains of aromatic amino acids (histidine, phenylalanine, tryptophan and tyrosine). The proteins are: rubredoxin, high potential iron protein, cytochrome c, flavodoxin, deoxyhemoglobin, trypsin inhibitor, ribonuclease-S, and lysozyme. The sulfur-pi-bonded 'chains' involve a minimum of five and a maximum of 10 amino acids, and contain the most polarizable atoms within proteins. S-pi-chains give extra stability to the folding of proteins; they may also afford paths for the step-wise movement of electrons.", "contents": "Chains of alternating sulfur and pi-bonded atoms in eight small proteins. This paper demonstrates the existence of regions in eight small globular proteins in which the side chains of sulfur-containing amino acids (cysteine and methionine) alternate in space with side chains of aromatic amino acids (histidine, phenylalanine, tryptophan and tyrosine). The proteins are: rubredoxin, high potential iron protein, cytochrome c, flavodoxin, deoxyhemoglobin, trypsin inhibitor, ribonuclease-S, and lysozyme. The sulfur-pi-bonded 'chains' involve a minimum of five and a maximum of 10 amino acids, and contain the most polarizable atoms within proteins. S-pi-chains give extra stability to the folding of proteins; they may also afford paths for the step-wise movement of electrons."}
{"id": "PMID:206522", "title": "The characteristics of adsorption of pyrophosphate and citrate onto whewellite.", "content": "The adsorption of pyrophosphate and citrate to whewellite was measured by solution depletion. At pH 6.5, the concentration for one-half surface coverage CE(1/2) by pyrophosphate is 15 micrometer. The estimated maximum coverage is 37.5 mumoles per m2. The CE (1/2) for citrate is 4 micrometer, and the estimated maximum coverage is 6.42 mumoles per m2.", "contents": "The characteristics of adsorption of pyrophosphate and citrate onto whewellite. The adsorption of pyrophosphate and citrate to whewellite was measured by solution depletion. At pH 6.5, the concentration for one-half surface coverage CE(1/2) by pyrophosphate is 15 micrometer. The estimated maximum coverage is 37.5 mumoles per m2. The CE (1/2) for citrate is 4 micrometer, and the estimated maximum coverage is 6.42 mumoles per m2."}
{"id": "PMID:206526", "title": "Ultrastructural findings on lipoproteins in vitro and in xanthomatous tissue.", "content": "The application of OSO4 plus K3 [Fe(CN)6] as a secondary fixative following aldehyde fixation, permitted demonstration of the presence of 30-300 nm 'membrane-bound' particles in xanthomatous tissue. With the same fixation method, isolated low density lipoprotein particles in a fibrin matrix could be observed in the transmission electron microscope in a way permitting comparison with similarly fixed tissue. However, isolated particles of very low density lipoproteins treated in the same way as low density particles had an irregular appearance and a diameter varying between 30 and 80 nm.", "contents": "Ultrastructural findings on lipoproteins in vitro and in xanthomatous tissue. The application of OSO4 plus K3 [Fe(CN)6] as a secondary fixative following aldehyde fixation, permitted demonstration of the presence of 30-300 nm 'membrane-bound' particles in xanthomatous tissue. With the same fixation method, isolated low density lipoprotein particles in a fibrin matrix could be observed in the transmission electron microscope in a way permitting comparison with similarly fixed tissue. However, isolated particles of very low density lipoproteins treated in the same way as low density particles had an irregular appearance and a diameter varying between 30 and 80 nm."}
{"id": "PMID:206529", "title": "Two kinds of mutants defective in multiple carbohydrate utilization isolated from in vitro fosfomycin-resistant strains of Escherichia coli K--12.", "content": "Two types of in vitro fosfomycin-resistant mutants defective in multiple carbohydrate utilization were selected from Escherichia coli strain K--12. One mutant, FR182, was defective in phosphoenolpyruvate: sugar phosphotransferase system and the ability to form adenosine 3',5'-cyclic monophosphate (cAMP) was lowered. Another mutant, FR190, was defective in cAMP formation. Restoration by cAMP of fosfomycin (FOM) sensitivity coupled with recovery of utilization of many carbohydrates including sn-glycerol-3-phosphate (G-3-P) was observed in both of the resistant mutants. FOM was not taken up by these resistant strains but, in the cells cultured in the presence of cAMP, accumulation of FOM was equivalent to that of the sensitive parent strain. Decreased uptake of G-3-P was also restored in both of the resistant strains cultured in the presence of cAMP. These results indicate that the resistance to FOM in these mutants is due to impairment of G-3-P transport system, one of the pathways for uptake of FOM. They were sensitized to FOM by D-glucose-6-phosphate because of the induction of hexose phosphate transport system, another uptake pathway.", "contents": "Two kinds of mutants defective in multiple carbohydrate utilization isolated from in vitro fosfomycin-resistant strains of Escherichia coli K--12. Two types of in vitro fosfomycin-resistant mutants defective in multiple carbohydrate utilization were selected from Escherichia coli strain K--12. One mutant, FR182, was defective in phosphoenolpyruvate: sugar phosphotransferase system and the ability to form adenosine 3',5'-cyclic monophosphate (cAMP) was lowered. Another mutant, FR190, was defective in cAMP formation. Restoration by cAMP of fosfomycin (FOM) sensitivity coupled with recovery of utilization of many carbohydrates including sn-glycerol-3-phosphate (G-3-P) was observed in both of the resistant mutants. FOM was not taken up by these resistant strains but, in the cells cultured in the presence of cAMP, accumulation of FOM was equivalent to that of the sensitive parent strain. Decreased uptake of G-3-P was also restored in both of the resistant strains cultured in the presence of cAMP. These results indicate that the resistance to FOM in these mutants is due to impairment of G-3-P transport system, one of the pathways for uptake of FOM. They were sensitized to FOM by D-glucose-6-phosphate because of the induction of hexose phosphate transport system, another uptake pathway."}
{"id": "PMID:206532", "title": "Analysis of fat-soluble vitamins. XX. Determination of vitamin D in multivitamin preparations. Second collaborative study.", "content": "The official first action method for determining vitamin D in multivitamin preparations was modified. The method was collaboratively studied by 7 laboratories, using 6 preparations in oil. The preparations consisted of vitamin D at various levels and at various ratios (in w/w) in vitamin A. Three samples contained cholecalciferol and 3 samples contained vitamin D3 from vitamin D3 resin. After outliers were eliminated by the Dixon test, data were analyzed and averages were compared with amounts of vitamin D known to be in each sample. For samples with vitamin D: vitamin A ratios of 1:0.5, 1:5, and 1:10, the mean vitamin D recoveries were 98.8, 94.6, and 90.7%, respectively. The method has been adopted as official final action.", "contents": "Analysis of fat-soluble vitamins. XX. Determination of vitamin D in multivitamin preparations. Second collaborative study. The official first action method for determining vitamin D in multivitamin preparations was modified. The method was collaboratively studied by 7 laboratories, using 6 preparations in oil. The preparations consisted of vitamin D at various levels and at various ratios (in w/w) in vitamin A. Three samples contained cholecalciferol and 3 samples contained vitamin D3 from vitamin D3 resin. After outliers were eliminated by the Dixon test, data were analyzed and averages were compared with amounts of vitamin D known to be in each sample. For samples with vitamin D: vitamin A ratios of 1:0.5, 1:5, and 1:10, the mean vitamin D recoveries were 98.8, 94.6, and 90.7%, respectively. The method has been adopted as official final action."}
{"id": "PMID:206533", "title": "Comparison of high pressure liquid chromatographic and chemical methods for vitamin D3 concentrates. II. Collaborative study.", "content": "A collaborative study was carried out which compared the official chemical method, 43.B14-43.B24, the official rat bioassay, 43.165, and the high pressure liquid chromatographic method for vitamin D3 resin, vitamin D3 resin in oil, and dry concentrate. A total of 340 samples were distributed to 17 collaborators for analysis. Five laboratories performed both the chemical and HPLC methods on 5 sets of blind duplicates. A 2-way analysis of variance comparing both methods for each sample showed a significant (P less than 0.01) difference between methods only for Sample 5. When the 2 methods were compared over all the samples, no significant (P less than 0.05) difference was found. Except for Sample 5, there were no differences in the repeatability of the methods. Per cent recoveries on Sample 3, which contained exactly 0.200 X 10(6) IU/g, showed 98.2% for the chemical method and 100.6% for the HPLC method for the 5 laboratories that performed both methods. The assay results of the HPLC and chemical methods are in good agreement with those found by the biological assay on Samples 1-4, but not for Sample 5. Evidence indicates that Sample 5 degraded partially to isotachysterol, and while the HPLC method yielded a reasonable value on this material, the chemical method erroneously showed full potency. An amendment is included for the collaboratively studied HPLC method which detects and eliminates 5,6-trans-vitamin D3, a possible interferant.", "contents": "Comparison of high pressure liquid chromatographic and chemical methods for vitamin D3 concentrates. II. Collaborative study. A collaborative study was carried out which compared the official chemical method, 43.B14-43.B24, the official rat bioassay, 43.165, and the high pressure liquid chromatographic method for vitamin D3 resin, vitamin D3 resin in oil, and dry concentrate. A total of 340 samples were distributed to 17 collaborators for analysis. Five laboratories performed both the chemical and HPLC methods on 5 sets of blind duplicates. A 2-way analysis of variance comparing both methods for each sample showed a significant (P less than 0.01) difference between methods only for Sample 5. When the 2 methods were compared over all the samples, no significant (P less than 0.05) difference was found. Except for Sample 5, there were no differences in the repeatability of the methods. Per cent recoveries on Sample 3, which contained exactly 0.200 X 10(6) IU/g, showed 98.2% for the chemical method and 100.6% for the HPLC method for the 5 laboratories that performed both methods. The assay results of the HPLC and chemical methods are in good agreement with those found by the biological assay on Samples 1-4, but not for Sample 5. Evidence indicates that Sample 5 degraded partially to isotachysterol, and while the HPLC method yielded a reasonable value on this material, the chemical method erroneously showed full potency. An amendment is included for the collaboratively studied HPLC method which detects and eliminates 5,6-trans-vitamin D3, a possible interferant."}
{"id": "PMID:206534", "title": "Purification and regulatory properties of the oxaloacetate decarboxylase of Acetobacter xylinum.", "content": "The oxaloacetate (OAA) decarboxylase (EC 4.1.1.3) activity of Acetobacter xylinum cells grown on glucose or glycerol is the same as that of cells grown on intermediates of the citrate cycle. The enzyme was purified 92-fold from extracts, and its molecular weight was determined to be 100,000 by gel filtration. Initial velocity studies revealed marked positive cooperativity for OAA (Hill coefficient [n(H)] = 1.8; S(0.5) = 21 mM). The affinity of the enzyme for OAA was markedly increased upon addition of nicotinamide adenine dinucleotide (NAD), NAD phosphate (NADP), and some other pyridine nucleotides. S(0.5(OAA)) decreased to 1 mM but n(H) and V(max) were unchanged. Saturation kinetics for the pyridine nucleotides were hyperbolic, and a half-maximal effect was obtained with 8 muM NAD and 30 muM NADP. The enzyme also catalyzed the exchange of (14)CO(2) into OAA but not the net carboxylation of pyruvate. Exchange activity, too, exhibited sigmoidal kinetics for OAA and was strongly stimulated by NAD at low substrate concentrations. The enzyme was inhibited by acetate competitively with respect to OAA. The K(I) for acetate (12 mM) was well within the physiological range of this compound inside the cell. The regulatory properties of the decarboxylase with respect to OAA cooperativity, NAD activation, and acetate inhibition were retained in situ within permeabilized cells. These properties seem to provide for a control mechanism which could insure the maintenance of OAA and the citrate cycle during growth of cells on glucose and, conversely, the required supply of pyruvate during growth on intermediates of the citrate cycle.", "contents": "Purification and regulatory properties of the oxaloacetate decarboxylase of Acetobacter xylinum. The oxaloacetate (OAA) decarboxylase (EC 4.1.1.3) activity of Acetobacter xylinum cells grown on glucose or glycerol is the same as that of cells grown on intermediates of the citrate cycle. The enzyme was purified 92-fold from extracts, and its molecular weight was determined to be 100,000 by gel filtration. Initial velocity studies revealed marked positive cooperativity for OAA (Hill coefficient [n(H)] = 1.8; S(0.5) = 21 mM). The affinity of the enzyme for OAA was markedly increased upon addition of nicotinamide adenine dinucleotide (NAD), NAD phosphate (NADP), and some other pyridine nucleotides. S(0.5(OAA)) decreased to 1 mM but n(H) and V(max) were unchanged. Saturation kinetics for the pyridine nucleotides were hyperbolic, and a half-maximal effect was obtained with 8 muM NAD and 30 muM NADP. The enzyme also catalyzed the exchange of (14)CO(2) into OAA but not the net carboxylation of pyruvate. Exchange activity, too, exhibited sigmoidal kinetics for OAA and was strongly stimulated by NAD at low substrate concentrations. The enzyme was inhibited by acetate competitively with respect to OAA. The K(I) for acetate (12 mM) was well within the physiological range of this compound inside the cell. The regulatory properties of the decarboxylase with respect to OAA cooperativity, NAD activation, and acetate inhibition were retained in situ within permeabilized cells. These properties seem to provide for a control mechanism which could insure the maintenance of OAA and the citrate cycle during growth of cells on glucose and, conversely, the required supply of pyruvate during growth on intermediates of the citrate cycle."}
{"id": "PMID:206535", "title": "Structure-function relationships in the arginine pathway carbamoylphosphate synthase of Saccharomyces cerevisiae.", "content": "The arginine pathway carbamoylphosphate synthase (CPSase A) from Saccharomyces cerevisiae was shown to be highly unstable and could not be substantially purified. In spite of this instability, a number of important properties of this enzyme were determined with crude preparations. A molecular weight of 140,000 (7.9S) was estimated for the native enzyme by sucrose gradient centrifugation; a significantly higher value, 175,000, was obtained by gel filtration on Sephadex. The enzyme is an aggregate consisting of two protein components, coded for by the unlinked genes cpaI and cpaII. These components were separated by diethylaminoethyl-cellulose chromatography. Their molecular weights, estimated by Sephadex gel filtration, were 36,000 and 130,000. The large component catalyzed the synthesis of carbamoylphosphate from ammonia. The small component was required in addition to the large one for the physiologically functional glutamine-dependent activity. Apparent Michaelis constants at pH 7.5 of 1.25 mM for glutamine and 75 mM for NH(4)Cl were measured with the native enzyme. The use of various glutamine analogs, including 2-amino-4-oxo-5-chloropentanoic acid, indicated that binding of glutamine to a site located on the small component was followed by transfer of its amide nitrogen to the ammonia site on the heavy component. This ammonia site was able to function independently of the utilization of glutamine. However, binding of glutamine was conjectured to cause a conformational change in the heavy component that greatly increased the rate of synthesis of carbamoylphosphate from ammonia. Glutamine, which was also shown to stabilize the aggregation of the two components, appeared to be a major effector of the catalytic and structural properties of CPSase A. In view of these observations, the CPSase A of yeast appears to share a number of structural and catalytic properties with the Escherichia coli enzyme. Obviously, the unlinked cpaI and cpaII genes of yeast are homologous to the adjacent carA and carB genes that code for the two subunits of the bacterial enzyme.", "contents": "Structure-function relationships in the arginine pathway carbamoylphosphate synthase of Saccharomyces cerevisiae. The arginine pathway carbamoylphosphate synthase (CPSase A) from Saccharomyces cerevisiae was shown to be highly unstable and could not be substantially purified. In spite of this instability, a number of important properties of this enzyme were determined with crude preparations. A molecular weight of 140,000 (7.9S) was estimated for the native enzyme by sucrose gradient centrifugation; a significantly higher value, 175,000, was obtained by gel filtration on Sephadex. The enzyme is an aggregate consisting of two protein components, coded for by the unlinked genes cpaI and cpaII. These components were separated by diethylaminoethyl-cellulose chromatography. Their molecular weights, estimated by Sephadex gel filtration, were 36,000 and 130,000. The large component catalyzed the synthesis of carbamoylphosphate from ammonia. The small component was required in addition to the large one for the physiologically functional glutamine-dependent activity. Apparent Michaelis constants at pH 7.5 of 1.25 mM for glutamine and 75 mM for NH(4)Cl were measured with the native enzyme. The use of various glutamine analogs, including 2-amino-4-oxo-5-chloropentanoic acid, indicated that binding of glutamine to a site located on the small component was followed by transfer of its amide nitrogen to the ammonia site on the heavy component. This ammonia site was able to function independently of the utilization of glutamine. However, binding of glutamine was conjectured to cause a conformational change in the heavy component that greatly increased the rate of synthesis of carbamoylphosphate from ammonia. Glutamine, which was also shown to stabilize the aggregation of the two components, appeared to be a major effector of the catalytic and structural properties of CPSase A. In view of these observations, the CPSase A of yeast appears to share a number of structural and catalytic properties with the Escherichia coli enzyme. Obviously, the unlinked cpaI and cpaII genes of yeast are homologous to the adjacent carA and carB genes that code for the two subunits of the bacterial enzyme."}
{"id": "PMID:206536", "title": "Superoxide dismutase and oxygen metabolism in Streptococcus faecalis and comparisons with other organisms.", "content": "Streptococcus faecalis contains a single superoxide dismutase that has been purified to homogeneity with a 55% yield. This enzyme has a molecular weight of 45,000 and is composed of two subunits of equal size. It contains 1.3 atoms of manganese per molecule. Its amino acid composition was determined and is compared with that for the superoxide dismutases from Escherichia coli, Streptococcus mutans, and Mycobacterium lepraemurium. When used as an antigen in rabbits, the S. faecalis enzyme elicited the formation of a precipitating and inhibiting antibody. This antibody cross-reacted with the superoxide dismutase present in another strain of S. faecalis, but neither inhibited nor precipitated the superoxide dismutases in a wide range of other bacteria, including several other streptococci, such as S. pyogenes, S. pneumoniae, and S. lactis. The inhibiting antibody was used to suppress the superoxide dismutase activity present in cell extracts of S. faecalis and thus allow the demonstration that 17% of the total oxygen consumption by such extracts, in the presence of reduced nicotinamide adenine dinucleotide, was associated with the production of O(2) (-). A variety of bacterial species were surveyed for their content of superoxide dismutases. The iron-containing enzyme was distinguished from the manganese-containing enzyme through the use of H(2)O(2), which inactivates the former more readily than the latter. Some of the bacteria appeared to contain only the iron enzyme, others only the manganese enzyme, and still others both. Indeed, some had multiple, electrophoretically distinct superoxide dismutases in both categories. There was no discernible absolute relationship between the types of superoxide dismutases in a particular organism and their Gram-stain reaction.", "contents": "Superoxide dismutase and oxygen metabolism in Streptococcus faecalis and comparisons with other organisms. Streptococcus faecalis contains a single superoxide dismutase that has been purified to homogeneity with a 55% yield. This enzyme has a molecular weight of 45,000 and is composed of two subunits of equal size. It contains 1.3 atoms of manganese per molecule. Its amino acid composition was determined and is compared with that for the superoxide dismutases from Escherichia coli, Streptococcus mutans, and Mycobacterium lepraemurium. When used as an antigen in rabbits, the S. faecalis enzyme elicited the formation of a precipitating and inhibiting antibody. This antibody cross-reacted with the superoxide dismutase present in another strain of S. faecalis, but neither inhibited nor precipitated the superoxide dismutases in a wide range of other bacteria, including several other streptococci, such as S. pyogenes, S. pneumoniae, and S. lactis. The inhibiting antibody was used to suppress the superoxide dismutase activity present in cell extracts of S. faecalis and thus allow the demonstration that 17% of the total oxygen consumption by such extracts, in the presence of reduced nicotinamide adenine dinucleotide, was associated with the production of O(2) (-). A variety of bacterial species were surveyed for their content of superoxide dismutases. The iron-containing enzyme was distinguished from the manganese-containing enzyme through the use of H(2)O(2), which inactivates the former more readily than the latter. Some of the bacteria appeared to contain only the iron enzyme, others only the manganese enzyme, and still others both. Indeed, some had multiple, electrophoretically distinct superoxide dismutases in both categories. There was no discernible absolute relationship between the types of superoxide dismutases in a particular organism and their Gram-stain reaction."}
{"id": "PMID:206537", "title": "Cyclic AMP-dependent synthesis of fimbriae in Salmonella typhimurium: effects of cya and pts mutations.", "content": "Synthesis of bacterial fimbriae (group 1, subtype 1) was shown to be dependent on cyclic AMP and was subject to catabolite repression by many carbohydrates. Mutations in the genes coding for the energy-coupling protein constituents of the phosphoenolpyruvate:sugar phosphotransferase system prevented repression of fimbrial production by the sugar substrates of this enzyme system.", "contents": "Cyclic AMP-dependent synthesis of fimbriae in Salmonella typhimurium: effects of cya and pts mutations. Synthesis of bacterial fimbriae (group 1, subtype 1) was shown to be dependent on cyclic AMP and was subject to catabolite repression by many carbohydrates. Mutations in the genes coding for the energy-coupling protein constituents of the phosphoenolpyruvate:sugar phosphotransferase system prevented repression of fimbrial production by the sugar substrates of this enzyme system."}
{"id": "PMID:206538", "title": "Reversal by certain polyanions of an endogenous inhibitor of the vesicular stomatitis virus-associated transcriptase.", "content": "The RNA-dependent RNA polymerase associated with vesicular stomatitis virus has been found to be markedly inhibited at high concentrations of virus. This endogenous inhibitor of the virion transcriptase was completely reversed by the action of two negatively charged polyamino acids: poly(L-glutamic acid) and pepsin (EC 3.4.23.1). Two other polyanions, heparin and polyethylene sulfonate, strongly inhibited the activity of the virion transcriptase even at low virus concentrations. Poly (L-glutamic acid) rapidly released the block in transcription of concentrated vesicular stomatitis virus, possibly owing to competition for binding sites of the inhibitor on the virion nucleocapsid transcription complex.", "contents": "Reversal by certain polyanions of an endogenous inhibitor of the vesicular stomatitis virus-associated transcriptase. The RNA-dependent RNA polymerase associated with vesicular stomatitis virus has been found to be markedly inhibited at high concentrations of virus. This endogenous inhibitor of the virion transcriptase was completely reversed by the action of two negatively charged polyamino acids: poly(L-glutamic acid) and pepsin (EC 3.4.23.1). Two other polyanions, heparin and polyethylene sulfonate, strongly inhibited the activity of the virion transcriptase even at low virus concentrations. Poly (L-glutamic acid) rapidly released the block in transcription of concentrated vesicular stomatitis virus, possibly owing to competition for binding sites of the inhibitor on the virion nucleocapsid transcription complex."}
{"id": "PMID:206539", "title": "Detection of calcium-dependent regulatory protein binding components using 125I-labeled calcium-dependent regulatory protein.", "content": "The calcium-dependent regulatory protein (CDR) purified from bovine brain was iodinated with Na[125I]I using the lactoperoxidase-glucose oxidase system. The iodinated protein retained its ability to stimulate the Ca2+-sensitive CDR-depleted cyclic nucleotide phosphodiesterase from bovine heart. Stimulation of the phosphodiesterase by 125I-CDR was Ca2+-dependent and the labeled protein had a Ka for activation of cyclic nucleotide phosphodiesterase that was 4 times greater than unmodified CDR. 125I-CDR formed a Ca2+-dependent complex with the partially purified cyclic nucleotide phosphodiesterase which was detectable by autorradiography following electrophoresis of the complex on nondenaturing gels. This technique was used to detect CDR binding components in crude homogenates prepared from bovine heart and brain.", "contents": "Detection of calcium-dependent regulatory protein binding components using 125I-labeled calcium-dependent regulatory protein. The calcium-dependent regulatory protein (CDR) purified from bovine brain was iodinated with Na[125I]I using the lactoperoxidase-glucose oxidase system. The iodinated protein retained its ability to stimulate the Ca2+-sensitive CDR-depleted cyclic nucleotide phosphodiesterase from bovine heart. Stimulation of the phosphodiesterase by 125I-CDR was Ca2+-dependent and the labeled protein had a Ka for activation of cyclic nucleotide phosphodiesterase that was 4 times greater than unmodified CDR. 125I-CDR formed a Ca2+-dependent complex with the partially purified cyclic nucleotide phosphodiesterase which was detectable by autorradiography following electrophoresis of the complex on nondenaturing gels. This technique was used to detect CDR binding components in crude homogenates prepared from bovine heart and brain."}
{"id": "PMID:206540", "title": "The modulator-dependent protein kinase. A multifunctional protein kinase activatable by the Ca2+-dependent modulator protein of the cyclic nucleotide system.", "content": "A protein kinase which depends on the simultaneous presence of Ca2+ and the modulator protein for its histone phosphorylation activity has been demonstrated in rabbit skeletal muscle and partially purified. The purified enzyme was not activated by cAMP, cGMP, or incubation with trypsin. Nor was the enzyme inhibited by the protein inhibitor of cAMP-dependent protein kinase. In addition to histone, myosin light chains and phosphorylase kinase served as substrates for the protein kinase, and their phosphorylation also depended on the presence of Ca2+ and the modulator protein. The phosphorylation of phosphorylase kinase was accompanied with a marked activation of the enzyme. The results suggest that the protein kinase has multiple functions and may be involved in the mediation of Ca2+ effects in many biological processes. It is proposed that this enzyme be designated as the modulator-dependent protein kinase. The modulator-dependent protein kinase may be identical to the myosin light chain kinase; chicken gizzard light chain kinase has been shown activatable by the modulator protein (Dabrowska, R., Sherry, J. M. F., Aramatorio, D. K., and Hartshorne, D. J. (1978) Biochemistry 17, 253-258).", "contents": "The modulator-dependent protein kinase. A multifunctional protein kinase activatable by the Ca2+-dependent modulator protein of the cyclic nucleotide system. A protein kinase which depends on the simultaneous presence of Ca2+ and the modulator protein for its histone phosphorylation activity has been demonstrated in rabbit skeletal muscle and partially purified. The purified enzyme was not activated by cAMP, cGMP, or incubation with trypsin. Nor was the enzyme inhibited by the protein inhibitor of cAMP-dependent protein kinase. In addition to histone, myosin light chains and phosphorylase kinase served as substrates for the protein kinase, and their phosphorylation also depended on the presence of Ca2+ and the modulator protein. The phosphorylation of phosphorylase kinase was accompanied with a marked activation of the enzyme. The results suggest that the protein kinase has multiple functions and may be involved in the mediation of Ca2+ effects in many biological processes. It is proposed that this enzyme be designated as the modulator-dependent protein kinase. The modulator-dependent protein kinase may be identical to the myosin light chain kinase; chicken gizzard light chain kinase has been shown activatable by the modulator protein (Dabrowska, R., Sherry, J. M. F., Aramatorio, D. K., and Hartshorne, D. J. (1978) Biochemistry 17, 253-258)."}
{"id": "PMID:206541", "title": "Association in normal human fibroblasts of elevated levels of adenosine 3':5'-monophosphate with a selective decrease in collagen production.", "content": "To evaluate the hypothesis that extracellular mediators may affect collagen production by mesenchymal cells via a cyclic AMP coordinated mechanism, normal human fibroblasts were exposed to a variety of agents (prostaglandin E1, isoproterenol, cholera toxin) which independently elevated intracellular cyclic AMP during a 6-h incubation. Concomitantly, each agent caused an average 47% reduction in the percentage of total protein synthesis represented by collagen, yet little change in other major extracellular proteins. Since no active collagenase was found in these cultures, these findings suggest cyclic AMP levels may modulate the differentiated state of normal fibroblasts with respect to collagen production.", "contents": "Association in normal human fibroblasts of elevated levels of adenosine 3':5'-monophosphate with a selective decrease in collagen production. To evaluate the hypothesis that extracellular mediators may affect collagen production by mesenchymal cells via a cyclic AMP coordinated mechanism, normal human fibroblasts were exposed to a variety of agents (prostaglandin E1, isoproterenol, cholera toxin) which independently elevated intracellular cyclic AMP during a 6-h incubation. Concomitantly, each agent caused an average 47% reduction in the percentage of total protein synthesis represented by collagen, yet little change in other major extracellular proteins. Since no active collagenase was found in these cultures, these findings suggest cyclic AMP levels may modulate the differentiated state of normal fibroblasts with respect to collagen production."}
{"id": "PMID:206544", "title": "Effects of rubratoxin B on the kinetics of cationic and substrate activation of (Na+-K+)-ATPase and p-nitrophenyl phosphatase.", "content": "Rubratoxin B, a lactone-containing bisanhydride metabolite of certain toxigenic molds, inhibited (Na+-K+)-stimulated ATPase activity of mouse brain microsomes in a dose-dependent manner with an estimated IC50 of 6 x 10(-6) M. Hydrolysis of ATP was linear with time and enzyme concentration, with or without rubratoxin in reaction mixtures. Altered pH and activity curves for (Na+-K+)-ATPase demonstrated comparable inhibition by rubratoxin in buffered acidic, neutral, and alkaline pH ranges. Kinetic studies of cationic-substrate activation of (Na+-K+)-ATPase indicated classical competitive inhibition for Na+ and K+. Results also showed competitive inhibition for K+ activated p-nitrophenyl phosphatase as demonstrated by altered binding site parameters without change in the catalytic velocity of dephosphorylation of the enzyme . phosphoryl complex. Noncompetitive inhibition with regards to activation by ATP and p-nitrophenyl phosphate was indicated by altered Vmax values with no change in Km values. Inhibition was partially restored by repeated washings. Preincubation with sulfhydryl agents protected the enzyme from inhibition. Cumulative inhibition studies with rubratoxin and ouabain indicated possible interaction between the two inhibitors of (Na+-K+)-ATPase. Rubratoxin appeared to exert its effects on (Na+-K+)-ATPase by interacting at Na+ and K+ sites.", "contents": "Effects of rubratoxin B on the kinetics of cationic and substrate activation of (Na+-K+)-ATPase and p-nitrophenyl phosphatase. Rubratoxin B, a lactone-containing bisanhydride metabolite of certain toxigenic molds, inhibited (Na+-K+)-stimulated ATPase activity of mouse brain microsomes in a dose-dependent manner with an estimated IC50 of 6 x 10(-6) M. Hydrolysis of ATP was linear with time and enzyme concentration, with or without rubratoxin in reaction mixtures. Altered pH and activity curves for (Na+-K+)-ATPase demonstrated comparable inhibition by rubratoxin in buffered acidic, neutral, and alkaline pH ranges. Kinetic studies of cationic-substrate activation of (Na+-K+)-ATPase indicated classical competitive inhibition for Na+ and K+. Results also showed competitive inhibition for K+ activated p-nitrophenyl phosphatase as demonstrated by altered binding site parameters without change in the catalytic velocity of dephosphorylation of the enzyme . phosphoryl complex. Noncompetitive inhibition with regards to activation by ATP and p-nitrophenyl phosphate was indicated by altered Vmax values with no change in Km values. Inhibition was partially restored by repeated washings. Preincubation with sulfhydryl agents protected the enzyme from inhibition. Cumulative inhibition studies with rubratoxin and ouabain indicated possible interaction between the two inhibitors of (Na+-K+)-ATPase. Rubratoxin appeared to exert its effects on (Na+-K+)-ATPase by interacting at Na+ and K+ sites."}
{"id": "PMID:206546", "title": "The deoxyribonuclease induced after infection of KB cells by herpes simplex virus type 1 or type 2. I. Purification and characterization of the enzyme.", "content": "The deoxyribonuclease induced in KB cells by herpes simplex virus (HSV) type 1 and type 2 has been purified. Both enzymes are able to completely degrade single- and double-stranded DNA yielding 5'-monophosphonucleotides as the sole products. A divalent cation, either Mg2+ or Mn2+, is an absolute requirement for catalysis and a reducing agent is necessary for enzyme stability. The maximum rate of reaction is achieved with 5 mM MgCl2 for both HSV-1 and HSV-2 DNase. The optimum concentration for Mn2+ is 0.1 to 0.2 mM and no exonuclease activity is observed when the concentration of Mn2+ is greater than 1 mM. The rate of reaction at the optimal Mg2+ concentration is 3- to 5-fold greater than that at the optimal Mn2+ concentration. In the presence of Mg2+, the enzymes are inhibited upon the addition of Mn2+, Ca2+, and Zn2+. The enzymatic reaction is also inhibited by spermine and spermidine, but not by putrescine. Crude and purified HSV-1 and HSV-2 DNase can degrade both HSV-1 and HSV-2 DNA, but native HSV-1 DNA is hydrolyzed at only 22% of the rate and HSV-2 DNA at only 32% of the rate of Escherichia coli DNA. Although HSV-1 and HSV-2 DNase were similar, minor differences were observed in most other properties such as pH optimum, inhibition by high ionic strength, activation energy, and sedimentation coefficient. However, the enzymes differ immunologically.", "contents": "The deoxyribonuclease induced after infection of KB cells by herpes simplex virus type 1 or type 2. I. Purification and characterization of the enzyme. The deoxyribonuclease induced in KB cells by herpes simplex virus (HSV) type 1 and type 2 has been purified. Both enzymes are able to completely degrade single- and double-stranded DNA yielding 5'-monophosphonucleotides as the sole products. A divalent cation, either Mg2+ or Mn2+, is an absolute requirement for catalysis and a reducing agent is necessary for enzyme stability. The maximum rate of reaction is achieved with 5 mM MgCl2 for both HSV-1 and HSV-2 DNase. The optimum concentration for Mn2+ is 0.1 to 0.2 mM and no exonuclease activity is observed when the concentration of Mn2+ is greater than 1 mM. The rate of reaction at the optimal Mg2+ concentration is 3- to 5-fold greater than that at the optimal Mn2+ concentration. In the presence of Mg2+, the enzymes are inhibited upon the addition of Mn2+, Ca2+, and Zn2+. The enzymatic reaction is also inhibited by spermine and spermidine, but not by putrescine. Crude and purified HSV-1 and HSV-2 DNase can degrade both HSV-1 and HSV-2 DNA, but native HSV-1 DNA is hydrolyzed at only 22% of the rate and HSV-2 DNA at only 32% of the rate of Escherichia coli DNA. Although HSV-1 and HSV-2 DNase were similar, minor differences were observed in most other properties such as pH optimum, inhibition by high ionic strength, activation energy, and sedimentation coefficient. However, the enzymes differ immunologically."}
{"id": "PMID:206547", "title": "Inhibition of Ca2+-activated cyclic nucleotide phosphodiesterase reaction by a heat-stable inhibitor protein from bovine brain.", "content": "An inhibitor protein of cyclic nucleotide phosphodiesterase is demonstrated in bovine brain extract and separated from modulator binding protein, a recently discovered inhibitory factor of phosphodiesterase. The new inhibitor protein is similar to the cyclic AMP phosphodiesterase inhibitor from bovine retina (Dumler, I. L., and Etingof, F. N. 1976) Biochim. Biophys, Acta 429, 474-484) in its heat stability: it retains full activity upon heating in a boiling water bath for 2 min. The new inhibitor protein counteracts the activation of the Ca2+-activatable cyclic nucleotide phosphodiesterase by the Ca2+-dependent modulator protein without affecting the basal activity of the enzyme. The inhibition of phosphodiesterase by the inhibitor can be reversed by high concentrations of modulator protein but is not influenced by a 20-fold increase in Ca2+ concentration. In contrast, a Ca2+-independent form of cyclic nucleotide phosphodiesterase is not inhibited by the inhibitor protein. These results suggest that the heat-stable inhibitor protein is specific against the action of the Ca2+-dependent modulator protein. Gel filtration analyses on Sephadex G-75 and G-100 columns have shown that the inhibitor protein and the modulator protein may associate in the presence of Ca2+. The molecular weights determined by the gel filtration for the free inhibitor protein and the complex of the inhibitor and modulator protein are about 70,000 and 85,000, respectively.", "contents": "Inhibition of Ca2+-activated cyclic nucleotide phosphodiesterase reaction by a heat-stable inhibitor protein from bovine brain. An inhibitor protein of cyclic nucleotide phosphodiesterase is demonstrated in bovine brain extract and separated from modulator binding protein, a recently discovered inhibitory factor of phosphodiesterase. The new inhibitor protein is similar to the cyclic AMP phosphodiesterase inhibitor from bovine retina (Dumler, I. L., and Etingof, F. N. 1976) Biochim. Biophys, Acta 429, 474-484) in its heat stability: it retains full activity upon heating in a boiling water bath for 2 min. The new inhibitor protein counteracts the activation of the Ca2+-activatable cyclic nucleotide phosphodiesterase by the Ca2+-dependent modulator protein without affecting the basal activity of the enzyme. The inhibition of phosphodiesterase by the inhibitor can be reversed by high concentrations of modulator protein but is not influenced by a 20-fold increase in Ca2+ concentration. In contrast, a Ca2+-independent form of cyclic nucleotide phosphodiesterase is not inhibited by the inhibitor protein. These results suggest that the heat-stable inhibitor protein is specific against the action of the Ca2+-dependent modulator protein. Gel filtration analyses on Sephadex G-75 and G-100 columns have shown that the inhibitor protein and the modulator protein may associate in the presence of Ca2+. The molecular weights determined by the gel filtration for the free inhibitor protein and the complex of the inhibitor and modulator protein are about 70,000 and 85,000, respectively."}
{"id": "PMID:206548", "title": "The 5'-terminal leader sequence of late 16 S mRNA from cells infected with simian virus 40.", "content": "The 16 S mRNA that directs the synthesis of VP1, the major structural protein of Simian virus 40 (SV40), is composed of a leader sequence of 203 nucleotides joined to a transcript that contains all the codons for VP1. The leader is transcribed from DNA between 0.723 and 0.762 map units while the VP1 coding transcript is copied from DNA from 0.94 to 0.17 map units. The leader sequence joins the transcript of the coding region at a position 42 nucleotides upstream from the initiator codon for VP1 by a 3':5'-phosphodiester linkage. Longer leader sequences also occur in a portion of SV40 late mRNA.", "contents": "The 5'-terminal leader sequence of late 16 S mRNA from cells infected with simian virus 40. The 16 S mRNA that directs the synthesis of VP1, the major structural protein of Simian virus 40 (SV40), is composed of a leader sequence of 203 nucleotides joined to a transcript that contains all the codons for VP1. The leader is transcribed from DNA between 0.723 and 0.762 map units while the VP1 coding transcript is copied from DNA from 0.94 to 0.17 map units. The leader sequence joins the transcript of the coding region at a position 42 nucleotides upstream from the initiator codon for VP1 by a 3':5'-phosphodiester linkage. Longer leader sequences also occur in a portion of SV40 late mRNA."}
{"id": "PMID:206551", "title": "Direct observation of the methionine residues of cytochrome c by 13C nuclear magnetic resonance spectroscopy.", "content": "The two Cepsilon-methyl methionine groups in cytochrome c have been chemically enriched (45%) with 13C. Their 13C NMR signals have been monitored in both the oxidized and reduced states and under various solution conditions. Methionine residue 80 showed characteristic chemical shift positions for the reduced Fe(II) and cyano-Fe(III) forms. No signal for methionine 80 was observed in the oxidized Fe(III) form due to the paramagnetic effect of the iron atom to which it is bonded, but the position of the methionine 65 signal was shifted, indicating that it is sensitive to the change of oxidation state. Two well resolved signals were observed at pH 11 for the Fe(III) form but only one was resolved at pH 2, indicating that while methionine 80 is definitely displaced from the iron atom at alkaline pH, it may not be in acid conditions.", "contents": "Direct observation of the methionine residues of cytochrome c by 13C nuclear magnetic resonance spectroscopy. The two Cepsilon-methyl methionine groups in cytochrome c have been chemically enriched (45%) with 13C. Their 13C NMR signals have been monitored in both the oxidized and reduced states and under various solution conditions. Methionine residue 80 showed characteristic chemical shift positions for the reduced Fe(II) and cyano-Fe(III) forms. No signal for methionine 80 was observed in the oxidized Fe(III) form due to the paramagnetic effect of the iron atom to which it is bonded, but the position of the methionine 65 signal was shifted, indicating that it is sensitive to the change of oxidation state. Two well resolved signals were observed at pH 11 for the Fe(III) form but only one was resolved at pH 2, indicating that while methionine 80 is definitely displaced from the iron atom at alkaline pH, it may not be in acid conditions."}
{"id": "PMID:206553", "title": "Neutral lipid accumulation in the membranes of Escherichia coli mutants lacking diglyceride kinase.", "content": "We have developed a rapid autoradiographic screening assay for detecting diglyceride kinase in colonies of Escherichia coli and have isolated four strains lacking this enzyme. The gene (designated dgk) which is altered in these mutants is cotransduceable with the malB locus, near minute 90 on the chromosome. The membranes of strain RZ60 (which carries the dgk-6 lesion) contain substantial amounts of 1,2-diglyceride, representing approximately 8% of the total lipid. In contrast, wild type cells of E. coli (dgk+) only contain about 0.5% 1,2-diglyceride. The phospholipid composition of these mutants is not dramatically altered, and they are not temperature sensitive for growth. However, strains bearing the dgk-6 mutation do not grow well on nutrient media of low osmolarity. This can be corrected by the inclusion of 1% NaCl or 0.5 M sucrose. These results suggest that 1,2-diglyceride is the true substrate for the kinase in vivo and that the kinase functions as a minor route for phosphatidic acid synthesis. Genetic modification of the diglyceride content of the E. coli membrane has not been reported previously.", "contents": "Neutral lipid accumulation in the membranes of Escherichia coli mutants lacking diglyceride kinase. We have developed a rapid autoradiographic screening assay for detecting diglyceride kinase in colonies of Escherichia coli and have isolated four strains lacking this enzyme. The gene (designated dgk) which is altered in these mutants is cotransduceable with the malB locus, near minute 90 on the chromosome. The membranes of strain RZ60 (which carries the dgk-6 lesion) contain substantial amounts of 1,2-diglyceride, representing approximately 8% of the total lipid. In contrast, wild type cells of E. coli (dgk+) only contain about 0.5% 1,2-diglyceride. The phospholipid composition of these mutants is not dramatically altered, and they are not temperature sensitive for growth. However, strains bearing the dgk-6 mutation do not grow well on nutrient media of low osmolarity. This can be corrected by the inclusion of 1% NaCl or 0.5 M sucrose. These results suggest that 1,2-diglyceride is the true substrate for the kinase in vivo and that the kinase functions as a minor route for phosphatidic acid synthesis. Genetic modification of the diglyceride content of the E. coli membrane has not been reported previously."}
{"id": "PMID:206558", "title": "Equilibrium and kinetic studies of unfolding of homologous cytochromes c.", "content": "Extensive investigations of the unfolding equilibria and kinetics of oxidized and reduced cytochromes c are reported. It is found that all cytochromes c have similar unfolding free energies (deltaGD = 7 +/- 1 kcal/mol). Differences among species do not correlate in any way with the metabolic differences among species. The stabilization of cytochrome c on reduction is estimated at 1.1 kcal/mol. Stability differences among species are mirrored in their denaturation kinetics. For cytochrome c (III), the unfolding exhibits multiple phases. The rate constants for the two observable phases both change by a factor of 3 between horse cytochrome c (III) and cow cytochrome c (III). On reduction, all unfolding appears to occur in a single step. The rate of this unfolding still varies between species, however, the results can be accommodated to a sequential model, with some assumptions. The observations are consistent with chain reversal occurring at an early stage in the reaction and suggest that previously observed rapid processes may be ligand exchange processes.", "contents": "Equilibrium and kinetic studies of unfolding of homologous cytochromes c. Extensive investigations of the unfolding equilibria and kinetics of oxidized and reduced cytochromes c are reported. It is found that all cytochromes c have similar unfolding free energies (deltaGD = 7 +/- 1 kcal/mol). Differences among species do not correlate in any way with the metabolic differences among species. The stabilization of cytochrome c on reduction is estimated at 1.1 kcal/mol. Stability differences among species are mirrored in their denaturation kinetics. For cytochrome c (III), the unfolding exhibits multiple phases. The rate constants for the two observable phases both change by a factor of 3 between horse cytochrome c (III) and cow cytochrome c (III). On reduction, all unfolding appears to occur in a single step. The rate of this unfolding still varies between species, however, the results can be accommodated to a sequential model, with some assumptions. The observations are consistent with chain reversal occurring at an early stage in the reaction and suggest that previously observed rapid processes may be ligand exchange processes."}
{"id": "PMID:206559", "title": "The dnaB gene product of Escherichia coli. I. Purification, homogeneity, and physical properties.", "content": "The dnaB gene product was purified to homogeneity and its physical properties were characterized. Purification was aided by the use of the Escherichia coli strain. MV12/28, which overproduced the dnaB gene product 10-fold (Wickner, S. H., Wickner, R. B., and Raetz, C. R. H. (1976) Biochem. Biophys. Res. Commun. 70, 389-396) and by taking advantage of the enzyme's high affinity for both DEAE-cellulose and phosphocellulose. The most highly purified fractions gave a single stained band on native, polyacrylamide gels and dnaB enzymatic activity was coincident with this band. On denaturing sodium dodecyl sulfate-polyacrylamide gels, a single band was observed corresponding to a molecular weight of 48,000 +/- 2,000. The native molecular weight of 290,000 +/- 12,000 was calculated from determinations of the sedimentation coefficient, which was 11.3 S, and the Stokes radius, which was 60 A. Cross-linking the protein with dimethyl suberimidate yielded six bands. We conclude that the enzyme consists of six identical subunits. The apparent pI was 4.9 and the amino acid composition was typical except for the absence of cysteine.", "contents": "The dnaB gene product of Escherichia coli. I. Purification, homogeneity, and physical properties. The dnaB gene product was purified to homogeneity and its physical properties were characterized. Purification was aided by the use of the Escherichia coli strain. MV12/28, which overproduced the dnaB gene product 10-fold (Wickner, S. H., Wickner, R. B., and Raetz, C. R. H. (1976) Biochem. Biophys. Res. Commun. 70, 389-396) and by taking advantage of the enzyme's high affinity for both DEAE-cellulose and phosphocellulose. The most highly purified fractions gave a single stained band on native, polyacrylamide gels and dnaB enzymatic activity was coincident with this band. On denaturing sodium dodecyl sulfate-polyacrylamide gels, a single band was observed corresponding to a molecular weight of 48,000 +/- 2,000. The native molecular weight of 290,000 +/- 12,000 was calculated from determinations of the sedimentation coefficient, which was 11.3 S, and the Stokes radius, which was 60 A. Cross-linking the protein with dimethyl suberimidate yielded six bands. We conclude that the enzyme consists of six identical subunits. The apparent pI was 4.9 and the amino acid composition was typical except for the absence of cysteine."}
{"id": "PMID:206560", "title": "The dnaB gene product of Escherichia coli. II. Single stranded DNA-dependent ribonucleoside triphosphatase activity.", "content": "The single-stranded DNA-dependent ribonucleoside triphosphatase activity of the Escherichia coli dnaB gene product was characterized. Purine ribonucleoside triphosphates were the preferred substrates, but all ribonucleoside triphosphates were cleaved at the gamma position to yield ribonucleoside diphosphates and Pi. The enzyme required Mg2+, which could be replaced by Mn2+ but with lower activity. The pH optimum was 7.5 in either Tris-HCl or phosphate buffer. The Km for MgATP was 0.59 mM and the Vmax was 8.7 nmol/min/microgram of protein at 30 degrees. The DNA requirement was best satisfied with either fd or phiX174 single-stranded DNA (Km 0.033 mM nucleotides); maximal rate of nucleoside diphosphate formation occurred with 1 dnaB molecule/fd or phiX174 single-stranded DNA molecule. The dnaB gene product was found to have hysteretic properties and the hysteresis appeared to be due to a dissociation and reassociation of the enzyme.", "contents": "The dnaB gene product of Escherichia coli. II. Single stranded DNA-dependent ribonucleoside triphosphatase activity. The single-stranded DNA-dependent ribonucleoside triphosphatase activity of the Escherichia coli dnaB gene product was characterized. Purine ribonucleoside triphosphates were the preferred substrates, but all ribonucleoside triphosphates were cleaved at the gamma position to yield ribonucleoside diphosphates and Pi. The enzyme required Mg2+, which could be replaced by Mn2+ but with lower activity. The pH optimum was 7.5 in either Tris-HCl or phosphate buffer. The Km for MgATP was 0.59 mM and the Vmax was 8.7 nmol/min/microgram of protein at 30 degrees. The DNA requirement was best satisfied with either fd or phiX174 single-stranded DNA (Km 0.033 mM nucleotides); maximal rate of nucleoside diphosphate formation occurred with 1 dnaB molecule/fd or phiX174 single-stranded DNA molecule. The dnaB gene product was found to have hysteretic properties and the hysteresis appeared to be due to a dissociation and reassociation of the enzyme."}
{"id": "PMID:206562", "title": "Fine structural localization of potassium-stimulated rho nitrophenylphosphatase activity in denrites of the cerebral cortex.", "content": "A histochemical technique for the demonstration of K+-rho-nitrophenylphosphatase (K+-rhoNPPase) activity, a component of the Na+,K+-ATPase, has been applied at the fine structural level in the somatosensory cortex of the rat. Reaction product was consistenly found in dendrites and in association with the cytoplasmic aspect of the dendritic plasmalemma. Reaction product often filled portions of the tubular smooth endoplasmic reticulum in these processes. The results of these studies are interpreted to indicate that enzymatic activity is associated with large-and small-diameter dendrites. No convincing evidence of high activity was found in glial profiles. The importance of neurons and their dendrites in active transport of sodium and potassium ions in the cerebral cortex may be more significant than indicated by studies with isolated neurons and glia.", "contents": "Fine structural localization of potassium-stimulated rho nitrophenylphosphatase activity in denrites of the cerebral cortex. A histochemical technique for the demonstration of K+-rho-nitrophenylphosphatase (K+-rhoNPPase) activity, a component of the Na+,K+-ATPase, has been applied at the fine structural level in the somatosensory cortex of the rat. Reaction product was consistenly found in dendrites and in association with the cytoplasmic aspect of the dendritic plasmalemma. Reaction product often filled portions of the tubular smooth endoplasmic reticulum in these processes. The results of these studies are interpreted to indicate that enzymatic activity is associated with large-and small-diameter dendrites. No convincing evidence of high activity was found in glial profiles. The importance of neurons and their dendrites in active transport of sodium and potassium ions in the cerebral cortex may be more significant than indicated by studies with isolated neurons and glia."}
{"id": "PMID:206563", "title": "Cytochalasin-stimulated steroidogenesis from high density lipoproteins.", "content": "The cytochalasins stimulate steroid secretion of Y-1 adrenal tumor cells two-to threefold. The order of potencies is cytochalasin E is greater than D is greater than B, but the maximum response is the the same and always less than with ACTH. Like that with ACTH, the stimulation has a rapid onset, is easily reversible, is inhibited by cucloheximide and aminoglutethimide, and occurs at a stage before pregnenolone. Although the cytochalasin, like ACTH, produce cell rounding, it is shown that this morphological change is not necessarily coupled to steridogenesis. Unlike ACTH, cytochalasin B does not measurably increase cellular levels of cAMP at concentrations that lead to maximal steroidogenesis. The cytochalasin B-induced stimulation of steroidogenesis, unlike the short-term ACTH effect, fails to occur in the absence of serum. This lack of response can be corrected by even low concentrations of human high density lipoproteins (HDL) but not by low density lipoproteins (LDL). We, therefore, propose that cytochalasin B enhances the availability of cholesterol bound to HDL for steroidogenesis by Y-1 adrenal cells.", "contents": "Cytochalasin-stimulated steroidogenesis from high density lipoproteins. The cytochalasins stimulate steroid secretion of Y-1 adrenal tumor cells two-to threefold. The order of potencies is cytochalasin E is greater than D is greater than B, but the maximum response is the the same and always less than with ACTH. Like that with ACTH, the stimulation has a rapid onset, is easily reversible, is inhibited by cucloheximide and aminoglutethimide, and occurs at a stage before pregnenolone. Although the cytochalasin, like ACTH, produce cell rounding, it is shown that this morphological change is not necessarily coupled to steridogenesis. Unlike ACTH, cytochalasin B does not measurably increase cellular levels of cAMP at concentrations that lead to maximal steroidogenesis. The cytochalasin B-induced stimulation of steroidogenesis, unlike the short-term ACTH effect, fails to occur in the absence of serum. This lack of response can be corrected by even low concentrations of human high density lipoproteins (HDL) but not by low density lipoproteins (LDL). We, therefore, propose that cytochalasin B enhances the availability of cholesterol bound to HDL for steroidogenesis by Y-1 adrenal cells."}
{"id": "PMID:206564", "title": "Intergrated stereological and biochemical studies of hepatocytic membranes. I. Membrane recoveries in subcellular fractions.", "content": "Previous attempts to relate the structure and function of hepatocytic membranes have compared biochemical data of fractions to morphological data derived from either intact tissue or fractions. The effects of the original homogenization aside, biochemical recoveries comparing membrane marker enzymes of the homogenate to subsequent fractions suggest a general conservation of activity. A sterological study was undertaken to estimate membrane surface areas in the intact tissue, homogenate, and fractions of the same livers and then to test the comparability of these data with membrane marker enzymes by calculating both morphological and biochemical recoveries. The sterological data were corrected for errors due to section thickness and compression. The average total membrane sufrace area per 1 g of liver was 9.3 m2 in the intact tissue (T), 7.8 m2 in the homogenate (H), and 7.4 m2 in the fractions (F); recoveries for the membrane surface areas thus averaged 96% for the (F/H) and 81% for the (F/T) comparisons. In homogenate and fractions, the differentiability of membranes by morphological criteria was limited to rough- and smooth- surfaced membranes, as well as outer and inner mitochondrial membranes. The recoveries of rough-surfaced membranes were 101% for F/H and 92% for F/T; those of smooth-surface membranes were 89% for F/H and 107% for F/T. For mitochondrial membranes, a recovery of 100% for F/H was obtained, whereas it amounted to only 54% for F/T. With respect to F/H, the membrane recoveries compare well with the marker enzyme recoveries obtained biochemically. The extension of recovery calculations to the intact tissue (F/T) revealed satisfactory conservation of the procedures of homogenization and fractionation; it indicates, however, that a shift of a substantial part of mitochondrial membranes to the pool of unidentifiable smooth membranes may occur on homogenization.", "contents": "Intergrated stereological and biochemical studies of hepatocytic membranes. I. Membrane recoveries in subcellular fractions. Previous attempts to relate the structure and function of hepatocytic membranes have compared biochemical data of fractions to morphological data derived from either intact tissue or fractions. The effects of the original homogenization aside, biochemical recoveries comparing membrane marker enzymes of the homogenate to subsequent fractions suggest a general conservation of activity. A sterological study was undertaken to estimate membrane surface areas in the intact tissue, homogenate, and fractions of the same livers and then to test the comparability of these data with membrane marker enzymes by calculating both morphological and biochemical recoveries. The sterological data were corrected for errors due to section thickness and compression. The average total membrane sufrace area per 1 g of liver was 9.3 m2 in the intact tissue (T), 7.8 m2 in the homogenate (H), and 7.4 m2 in the fractions (F); recoveries for the membrane surface areas thus averaged 96% for the (F/H) and 81% for the (F/T) comparisons. In homogenate and fractions, the differentiability of membranes by morphological criteria was limited to rough- and smooth- surfaced membranes, as well as outer and inner mitochondrial membranes. The recoveries of rough-surfaced membranes were 101% for F/H and 92% for F/T; those of smooth-surface membranes were 89% for F/H and 107% for F/T. For mitochondrial membranes, a recovery of 100% for F/H was obtained, whereas it amounted to only 54% for F/T. With respect to F/H, the membrane recoveries compare well with the marker enzyme recoveries obtained biochemically. The extension of recovery calculations to the intact tissue (F/T) revealed satisfactory conservation of the procedures of homogenization and fractionation; it indicates, however, that a shift of a substantial part of mitochondrial membranes to the pool of unidentifiable smooth membranes may occur on homogenization."}
{"id": "PMID:206565", "title": "Growth dependence of phosphoglyceric acid dehydrogenase activity in cultured rat liver cells.", "content": "Rat liver epithelial cells in culture (WIRL-3C) have the enzymes that synthesize serine from 3-phophoglyceric acid. Both phosphoglyceric acid dehydrogenase (PGAD) and serine-phosphate (serine-P) forming activities fluctuate with time after subculture and are higher in growing than confluent cells. This activity pattern was not common for other dehydrogenases in WIRL-3C cells, nor was it common for PGAD activity in other cultured cells. At time of subculture, cells are removed from spent medium, treated with trypsin, and fed fresh medium. None of these parameters causes the rise in activity; in contrast, reduction in cell density and the accompanying stimulation of growth do. PGAD activity decreases when growth is slowed either as the cells progress to the end of the culture cycle, when cells are treated with dexamethasone-phosphate (Dx-P) or dibutyryl cyclic AMP(cAMP) and theophylline or when the serum concentration of the medium is reduced to 0.2%. Under these conditions, decreased PGAD activity is paralleled by a decline in growth and DNA accumulation. PGAD activity in WIRL-3C cells is regulated in a manner closely resembling what has been observed previously in rat liver from the whole animal. The possible use of this system in studying regulation of gene expression in mammalian cells is discussed.", "contents": "Growth dependence of phosphoglyceric acid dehydrogenase activity in cultured rat liver cells. Rat liver epithelial cells in culture (WIRL-3C) have the enzymes that synthesize serine from 3-phophoglyceric acid. Both phosphoglyceric acid dehydrogenase (PGAD) and serine-phosphate (serine-P) forming activities fluctuate with time after subculture and are higher in growing than confluent cells. This activity pattern was not common for other dehydrogenases in WIRL-3C cells, nor was it common for PGAD activity in other cultured cells. At time of subculture, cells are removed from spent medium, treated with trypsin, and fed fresh medium. None of these parameters causes the rise in activity; in contrast, reduction in cell density and the accompanying stimulation of growth do. PGAD activity decreases when growth is slowed either as the cells progress to the end of the culture cycle, when cells are treated with dexamethasone-phosphate (Dx-P) or dibutyryl cyclic AMP(cAMP) and theophylline or when the serum concentration of the medium is reduced to 0.2%. Under these conditions, decreased PGAD activity is paralleled by a decline in growth and DNA accumulation. PGAD activity in WIRL-3C cells is regulated in a manner closely resembling what has been observed previously in rat liver from the whole animal. The possible use of this system in studying regulation of gene expression in mammalian cells is discussed."}
{"id": "PMID:206566", "title": "Co-cultivation of tumorigenic mouse melanoma cells with cells of a non-tumorigenic subclone inhibits plasminogen activator expression by the melanoma cells.", "content": "Clone B559 mouse melanoma cells are highly tumorigenic and produce plasminogen activator. Cells of clone C3471, a line obtained by continued growth of B559 cells in medium containing 5-bromodeoxyuridine (1 microgram/ml), have no plasminogen activator and are non-tumorigenic. When B559 cells are co-cultivated with C3471 cells, the ability of B559 cells to activate plasminogen is suppressed. Under these conditions cell fusion occurs. Lack of expression of plasminogen activators is not a consequence of cell fusion, inhibition of cell division or release of soluble inhibitors of either plasminogen activators or plasmin. No inhibitors of plasminogen activators could be demonstrated in association with sub cellular fractions of C3471 cells or with the C-type viral particles released from C3471 cells. Close contact between cells of the two lines is shown to be essential for suppression of plasminogen activation.", "contents": "Co-cultivation of tumorigenic mouse melanoma cells with cells of a non-tumorigenic subclone inhibits plasminogen activator expression by the melanoma cells. Clone B559 mouse melanoma cells are highly tumorigenic and produce plasminogen activator. Cells of clone C3471, a line obtained by continued growth of B559 cells in medium containing 5-bromodeoxyuridine (1 microgram/ml), have no plasminogen activator and are non-tumorigenic. When B559 cells are co-cultivated with C3471 cells, the ability of B559 cells to activate plasminogen is suppressed. Under these conditions cell fusion occurs. Lack of expression of plasminogen activators is not a consequence of cell fusion, inhibition of cell division or release of soluble inhibitors of either plasminogen activators or plasmin. No inhibitors of plasminogen activators could be demonstrated in association with sub cellular fractions of C3471 cells or with the C-type viral particles released from C3471 cells. Close contact between cells of the two lines is shown to be essential for suppression of plasminogen activation."}
{"id": "PMID:206567", "title": "Stimulation of DNA synthesis in human fibroblasts by thrombin.", "content": "Earlier work showed that thrombin stimulates proliferation of human fibroblasts in serumfree medium. This work demonstrates (1) that thrombin has to be prensent during most or all of the G1 period to ensure maximal DNA synthesis, (2) that DNA synthesis increases about three hours later after thrombin than after serum treatment, (3) that both thrombin and serum activate transport of uridine, D--2-deoxy-glucose and putrescine, (4) that thrombin is able to increase 3H-thymidine incorporation also in SV40 transformed human fibroblasts, in HeLa cells and in two continuous monkey cell lines.", "contents": "Stimulation of DNA synthesis in human fibroblasts by thrombin. Earlier work showed that thrombin stimulates proliferation of human fibroblasts in serumfree medium. This work demonstrates (1) that thrombin has to be prensent during most or all of the G1 period to ensure maximal DNA synthesis, (2) that DNA synthesis increases about three hours later after thrombin than after serum treatment, (3) that both thrombin and serum activate transport of uridine, D--2-deoxy-glucose and putrescine, (4) that thrombin is able to increase 3H-thymidine incorporation also in SV40 transformed human fibroblasts, in HeLa cells and in two continuous monkey cell lines."}
{"id": "PMID:206568", "title": "Epidermal growth factor induced membrane changes in 3T3 cells.", "content": "Epidermal growth factor (EGF) is a mitogen for Swiss 3T3 cells. Short incubation periods with physiological concentrations of EGF induced increased binding of Swiss 3T3 cells to Con A-coated nylon fibers. This effect was not induced in an EGF non-responsive 33 variant, in the transformed murine XC cells or in Swiss SV3T3 cells. The increase in Con A fiber-binding seems to be specific for EGF, since it was not observed in response to insulin, prostaglandin F2alpha or a higher serum concentration, which also initiate cell devision of confluent quiescent 3T3 cells. EGF also reduced Con A-mediated hemadsorption to 3T3, but had no effect on hemadsorption by the EFG non-responsive 3T3 variant. There was no change in the number of Con A-receptors on 3T3 cells after EGF treatment. Binding to WGA-coated fibers and WGA-mediated hemadsorption were not effected by preincubation with EGF.", "contents": "Epidermal growth factor induced membrane changes in 3T3 cells. Epidermal growth factor (EGF) is a mitogen for Swiss 3T3 cells. Short incubation periods with physiological concentrations of EGF induced increased binding of Swiss 3T3 cells to Con A-coated nylon fibers. This effect was not induced in an EGF non-responsive 33 variant, in the transformed murine XC cells or in Swiss SV3T3 cells. The increase in Con A fiber-binding seems to be specific for EGF, since it was not observed in response to insulin, prostaglandin F2alpha or a higher serum concentration, which also initiate cell devision of confluent quiescent 3T3 cells. EGF also reduced Con A-mediated hemadsorption to 3T3, but had no effect on hemadsorption by the EFG non-responsive 3T3 variant. There was no change in the number of Con A-receptors on 3T3 cells after EGF treatment. Binding to WGA-coated fibers and WGA-mediated hemadsorption were not effected by preincubation with EGF."}
{"id": "PMID:206569", "title": "2-amino-isobutyric acid and 3-O-methyl-D-glucose transport in 3T3, SV 40-transformed 3T3 and revertant cell lines.", "content": "In order to further investigate the connection between transport and growth control, 3T3 cells, SV40 transformed 3T3 cells (SV101), and three revertant cell lines derived from SV101 which have regained certain manifestations of growth control were used. Transport rates of 2-amino-isobutyric acid and 3-O-methyl-D-glucose were measured in sparse, confluent, serum-starved, and serum-stimulated cultures. As shown before, cessation of 3T3 cell growth in G0 under conditions of confluence or serum deprivation was associated with reduced rates of transport for both compounds, whereas the density and serum dependence of growth and transport was largely eliminated in SV101. The density revertant F1SV101, which has regained density regulation of growth similar to 3T3 cells, has also regained density regulation of transport. Neither growth nor transport were serum dependent. The serum revertants AgammaSV7 and LsSV6 have regained both density and serum regulation of growth, but not according to the original mechanism of 3T3 cells of entry into a Go state. Transport was high under conditions of confluence or serum deprivation. Thus for these cells rates of transport were not reduced simply as a consequences of slower cell growth nor were low transport rates responsible for growth arrest. The data are consistent with the possibility that growth arrest specifically in the G0 state could shut off a number of cellular activities, including transport.", "contents": "2-amino-isobutyric acid and 3-O-methyl-D-glucose transport in 3T3, SV 40-transformed 3T3 and revertant cell lines. In order to further investigate the connection between transport and growth control, 3T3 cells, SV40 transformed 3T3 cells (SV101), and three revertant cell lines derived from SV101 which have regained certain manifestations of growth control were used. Transport rates of 2-amino-isobutyric acid and 3-O-methyl-D-glucose were measured in sparse, confluent, serum-starved, and serum-stimulated cultures. As shown before, cessation of 3T3 cell growth in G0 under conditions of confluence or serum deprivation was associated with reduced rates of transport for both compounds, whereas the density and serum dependence of growth and transport was largely eliminated in SV101. The density revertant F1SV101, which has regained density regulation of growth similar to 3T3 cells, has also regained density regulation of transport. Neither growth nor transport were serum dependent. The serum revertants AgammaSV7 and LsSV6 have regained both density and serum regulation of growth, but not according to the original mechanism of 3T3 cells of entry into a Go state. Transport was high under conditions of confluence or serum deprivation. Thus for these cells rates of transport were not reduced simply as a consequences of slower cell growth nor were low transport rates responsible for growth arrest. The data are consistent with the possibility that growth arrest specifically in the G0 state could shut off a number of cellular activities, including transport."}
{"id": "PMID:206570", "title": "Early changes in the membrane of HeLa cells adsorbing Sendai virus under conditions of fusion.", "content": "Adsorption of Sendai virus at high multiplicity (500-1,000 HAU/10(6) cells) to HeLa cells grown in monolayers causes immediate changes in the ion barrier of the cell membrane, as well as changes in the morphology of the virus-treated cells. Within minutes of adsorption the cells begin to lose potassium and an extensive influx of ions into the cells occurs. Concomitantly with these changes, the cell membrane becomes depolarized, and the resting potential across its membrane decreases. Twenty to sixty minutes post adsorption the damage to the cell membrane is repaired, and both the potassium uptake and the resting potential return to their pre-exposure values. Scanning electron-micrographs of Sendai infected cells incubated at 37 degrees C show formation of bridging microvilli in a zipper-like fashion within two to five minutes post-adsorption; 30 to 60 minutes thereafter the majority of cells in the monolayer are fused. Biochemical changes induced by virus adsorption and the role of Ca++ ions in the observed effects are discussed.", "contents": "Early changes in the membrane of HeLa cells adsorbing Sendai virus under conditions of fusion. Adsorption of Sendai virus at high multiplicity (500-1,000 HAU/10(6) cells) to HeLa cells grown in monolayers causes immediate changes in the ion barrier of the cell membrane, as well as changes in the morphology of the virus-treated cells. Within minutes of adsorption the cells begin to lose potassium and an extensive influx of ions into the cells occurs. Concomitantly with these changes, the cell membrane becomes depolarized, and the resting potential across its membrane decreases. Twenty to sixty minutes post adsorption the damage to the cell membrane is repaired, and both the potassium uptake and the resting potential return to their pre-exposure values. Scanning electron-micrographs of Sendai infected cells incubated at 37 degrees C show formation of bridging microvilli in a zipper-like fashion within two to five minutes post-adsorption; 30 to 60 minutes thereafter the majority of cells in the monolayer are fused. Biochemical changes induced by virus adsorption and the role of Ca++ ions in the observed effects are discussed."}
{"id": "PMID:206572", "title": "Determination of methotrexate in plasma by on-column concentrations and ion-exchange chromatography.", "content": "A method for the concentration of dilute samples on a column and its application to the analysis of biomedical mixtures is described. Two columns are used, one for the concentration step and the other for the separation. The concentration column is used in the position of the loop in an injection valve. Concentration is effected by eluent switching. The influence of the chromatographic parameters such as capacity ratio and void volume on separation and detectability are described and the optimal choice of conditions is discussed. The method has been applied to the analysis of the cytostatic drug methotrexate. An octyl-modified silica was used as the stationary phase in the concentration column and a chemically bonded anion exchanger on silica in the separation column. The procedure shows good selectivity and precision. The detection limit corresponds to 2.10-8 M (9 ppb) in plasma, which is sufficiently low for therapeutic concentrations to be measured. An example of the use of the same stationary phase in both columns is given for the analysis of phenothiazines in blood, using alkyl-modified silica and electrochemical detection.", "contents": "Determination of methotrexate in plasma by on-column concentrations and ion-exchange chromatography. A method for the concentration of dilute samples on a column and its application to the analysis of biomedical mixtures is described. Two columns are used, one for the concentration step and the other for the separation. The concentration column is used in the position of the loop in an injection valve. Concentration is effected by eluent switching. The influence of the chromatographic parameters such as capacity ratio and void volume on separation and detectability are described and the optimal choice of conditions is discussed. The method has been applied to the analysis of the cytostatic drug methotrexate. An octyl-modified silica was used as the stationary phase in the concentration column and a chemically bonded anion exchanger on silica in the separation column. The procedure shows good selectivity and precision. The detection limit corresponds to 2.10-8 M (9 ppb) in plasma, which is sufficiently low for therapeutic concentrations to be measured. An example of the use of the same stationary phase in both columns is given for the analysis of phenothiazines in blood, using alkyl-modified silica and electrochemical detection."}
{"id": "PMID:206573", "title": "Bacteriocin typing of Clostridium perfringens in human feces.", "content": "Three hundred and ninety-nine isolates of Clostridium perfringens from enriched stool specimens of 51 individuals (about eight colonies per person) were typed by bacteriocins. Forty-nine percent of these persons carried more than one bacteriocin type in their stool, and some had three or four different stains as determined by bacteriocin typing. Weekly stool specimens obtained from seven positive volunteers over a period of 5 weeks were screened for C. perfringens, and several colonies from each person were typed. This survey demonstrated that the number of types fluctuated with time, several types could be carried simultaneously, and the isolation of the organism was variable. Nine new bacteriocin types of C. perfringens were isolated in this study.", "contents": "Bacteriocin typing of Clostridium perfringens in human feces. Three hundred and ninety-nine isolates of Clostridium perfringens from enriched stool specimens of 51 individuals (about eight colonies per person) were typed by bacteriocins. Forty-nine percent of these persons carried more than one bacteriocin type in their stool, and some had three or four different stains as determined by bacteriocin typing. Weekly stool specimens obtained from seven positive volunteers over a period of 5 weeks were screened for C. perfringens, and several colonies from each person were typed. This survey demonstrated that the number of types fluctuated with time, several types could be carried simultaneously, and the isolation of the organism was variable. Nine new bacteriocin types of C. perfringens were isolated in this study."}
{"id": "PMID:206574", "title": "Quantitative estimation of infantile gastroenteritis virus antigens in stools by immune adherence hemagglutination test.", "content": "Infantile gastroenteritis virus antigens in stools were titrated by the immune adherence hemagglutination test. A good correlation was observed between immune adherence hemagglutination titers and electron microscope counts.", "contents": "Quantitative estimation of infantile gastroenteritis virus antigens in stools by immune adherence hemagglutination test. Infantile gastroenteritis virus antigens in stools were titrated by the immune adherence hemagglutination test. A good correlation was observed between immune adherence hemagglutination titers and electron microscope counts."}
{"id": "PMID:206575", "title": "Hemagglutination by simian rotavirus.", "content": "A simian rotavirus (SA-11) was shown to hemagglutinate human group \"O\" and guinea pig erythrocytes. The hemagglutinin appeared to be associated with the outer capsid of the SA-11 virus and was inhibited by specific hyperimmune anti-SA-11 guinea pig serum.", "contents": "Hemagglutination by simian rotavirus. A simian rotavirus (SA-11) was shown to hemagglutinate human group \"O\" and guinea pig erythrocytes. The hemagglutinin appeared to be associated with the outer capsid of the SA-11 virus and was inhibited by specific hyperimmune anti-SA-11 guinea pig serum."}
{"id": "PMID:206576", "title": "Grading of astrocytomas using a Quantimet 720 image-analysing computer.", "content": "Cerebral astrocytomas and undifferentiated gliomas were graded by (1) Kernohan classification on the basis of visual microscopy, and (2) optical density/area profiles obtained by automated densitometry with a Quantimet 720 image-analysing computer. In a retrospective study of 44 patients the Quantimet measurements seemed to give a more accurate assessment of prognosis than visual grading.", "contents": "Grading of astrocytomas using a Quantimet 720 image-analysing computer. Cerebral astrocytomas and undifferentiated gliomas were graded by (1) Kernohan classification on the basis of visual microscopy, and (2) optical density/area profiles obtained by automated densitometry with a Quantimet 720 image-analysing computer. In a retrospective study of 44 patients the Quantimet measurements seemed to give a more accurate assessment of prognosis than visual grading."}
{"id": "PMID:206579", "title": "The Merkel cell in oral human mucosa.", "content": "A study of the mucosal Merkel cells from 10 patients showed that the cell contained an intranuclear rodlet, clear cell qualities, fine desmosomes, characteristic membrane-bound Merkel granules, and cellular \"horns\" and had a close relationship to terminal axons. The Merkel cell is an intraepithelial cell with features of neurons and of amine-storage cells.", "contents": "The Merkel cell in oral human mucosa. A study of the mucosal Merkel cells from 10 patients showed that the cell contained an intranuclear rodlet, clear cell qualities, fine desmosomes, characteristic membrane-bound Merkel granules, and cellular \"horns\" and had a close relationship to terminal axons. The Merkel cell is an intraepithelial cell with features of neurons and of amine-storage cells."}
{"id": "PMID:206580", "title": "An in vitro study of certain properties of a glass ionomer cement.", "content": "A glass ionomer cement was tested for its release of fluoride, effect on solubility of enamel, bond to enamel, and ability to seal the cavity. It was comparable to silicate cement in its release of fluoride and its effect on solubility of enamel. The strength of the bond of the cement to tooth structure was similar to polycarboxylate cement, and it appeared to be quite effective in sealing cavities.", "contents": "An in vitro study of certain properties of a glass ionomer cement. A glass ionomer cement was tested for its release of fluoride, effect on solubility of enamel, bond to enamel, and ability to seal the cavity. It was comparable to silicate cement in its release of fluoride and its effect on solubility of enamel. The strength of the bond of the cement to tooth structure was similar to polycarboxylate cement, and it appeared to be quite effective in sealing cavities."}
{"id": "PMID:206581", "title": "The dental patient with renal disease: precautions and guidelines.", "content": "Hemodialysis and related methods of treatment are keeping renal patients alive and able to carry on many of their daily activities. These patients, however, are limited in the scope within which they can function. Dietary requirements, fluid intake, and most medications must be rigidly controlled. Many commonly used drugs can damage the kidneys and must be avoided. Dentists who treat patients with renal insufficiency must avoid prescribing or administering nephrotoxic drugs or agents that become dangerous with loss of kidney function.", "contents": "The dental patient with renal disease: precautions and guidelines. Hemodialysis and related methods of treatment are keeping renal patients alive and able to carry on many of their daily activities. These patients, however, are limited in the scope within which they can function. Dietary requirements, fluid intake, and most medications must be rigidly controlled. Many commonly used drugs can damage the kidneys and must be avoided. Dentists who treat patients with renal insufficiency must avoid prescribing or administering nephrotoxic drugs or agents that become dangerous with loss of kidney function."}
{"id": "PMID:206625", "title": "Enzyme-labelled immunosorbent assay techniques in foot-and-mouth disease virus research.", "content": "The indirect ELISA technique has been developed successfully to measure antibodies to foot-and-mouth disease virus (FMDV) in cattle sera. Preliminary studies using a standard serum assay show that reproducible results are obtained. The method should prove useful for the examination of antibody titres in sera from large numbers of cattle or other animals.", "contents": "Enzyme-labelled immunosorbent assay techniques in foot-and-mouth disease virus research. The indirect ELISA technique has been developed successfully to measure antibodies to foot-and-mouth disease virus (FMDV) in cattle sera. Preliminary studies using a standard serum assay show that reproducible results are obtained. The method should prove useful for the examination of antibody titres in sera from large numbers of cattle or other animals."}
{"id": "PMID:206626", "title": "In vitro comparison of foot-and-mouth disease virus subtype variants causing disease in vaccinated cattle.", "content": "Foot-and-mouth disease virus isolates of types O, A and SAT 2, from diseased animals in herds routinely vaccinated twice a year were compared antigenically with the vaccine strains in the complement-fixation, neutralization and radial immunodiffusion tests. It was found that strains which had readily infected vaccinated cattle had R values against the vaccine strain in the complementfixation and radial immunodiffusion tests of 30 or less, while strains causing primary outbreaks with little spread had R values of 30-40. Threefold differences in humoral neutralizing antibody concentration between the field variant and the vaccine strain in sera from vaccinated animals were likely to be significant in terms of protection.", "contents": "In vitro comparison of foot-and-mouth disease virus subtype variants causing disease in vaccinated cattle. Foot-and-mouth disease virus isolates of types O, A and SAT 2, from diseased animals in herds routinely vaccinated twice a year were compared antigenically with the vaccine strains in the complement-fixation, neutralization and radial immunodiffusion tests. It was found that strains which had readily infected vaccinated cattle had R values against the vaccine strain in the complementfixation and radial immunodiffusion tests of 30 or less, while strains causing primary outbreaks with little spread had R values of 30-40. Threefold differences in humoral neutralizing antibody concentration between the field variant and the vaccine strain in sera from vaccinated animals were likely to be significant in terms of protection."}
{"id": "PMID:206627", "title": "Effect of thymosin and lipopolysaccharide on murine lymphocyte cyclic AMP.", "content": "The effects of thymosin and lipopolysaccharide (LPS) on cyclic AMP levels in lymphocytes were evaluated using three independent assays which included adenine prelabeling, protein kinase binding, and radioimmunoassay. All three assays proved to be both sensitive and accurate in assessing relative changes in lymphocytes after incubation in vitro with various agents. The assays confirmed that basal and stimulated levels of cyclic AMP depended on the origin of the lymphocyte population. Each of the three techniques demonstrated that pyrogen-free bovine thymosin fraction 5 did not elevate thymocyte cAMP levels. In contrast, it was found that lipopolysaccharide (lps) significantly elevated cAMP levels in both spleen and thymus lymphocytes. These studies indicate that assays for measuring the activity of thymic extracts in which the intracellular levels of cyclic nucleotides are a criterion for activity are only valid if the preparations are not contaminated with endotoxins.", "contents": "Effect of thymosin and lipopolysaccharide on murine lymphocyte cyclic AMP. The effects of thymosin and lipopolysaccharide (LPS) on cyclic AMP levels in lymphocytes were evaluated using three independent assays which included adenine prelabeling, protein kinase binding, and radioimmunoassay. All three assays proved to be both sensitive and accurate in assessing relative changes in lymphocytes after incubation in vitro with various agents. The assays confirmed that basal and stimulated levels of cyclic AMP depended on the origin of the lymphocyte population. Each of the three techniques demonstrated that pyrogen-free bovine thymosin fraction 5 did not elevate thymocyte cAMP levels. In contrast, it was found that lipopolysaccharide (lps) significantly elevated cAMP levels in both spleen and thymus lymphocytes. These studies indicate that assays for measuring the activity of thymic extracts in which the intracellular levels of cyclic nucleotides are a criterion for activity are only valid if the preparations are not contaminated with endotoxins."}
{"id": "PMID:206629", "title": "The permeability of epidermis lacking normal membrane-coating granules: an ultrastructural tracer study of Kyrle-Flegel disease.", "content": "Skin lesions from patients with Flegel's disease have been reported to be without membrane-coating granules (Odland bodies). Biopsies of the hyperkeratinized papules of Kyrle-Flegel disease were incubated in vitro with the intercellular tracer, horseradish peroxidase, and the extent of penetration of this substance examined in the light and electron microscopes. The peroxidase was present throughout the corium and extended through the intercellular spaces of the epidermis to a level close to the junction of the granular and keratinized layers; it did not enter the bulk of the thickened stratum corneum of the lesion. Ultrastructural examination revealed the presence of small vesicles in the granular layer, similar in size and shape to membrane-coating granules but lacking a lamellate internal structure; these were occasionally seen fusing with the plasma membrane of the cells. It is suggested that the intercellular permeability barrier to horseradish peroxidase demonstrated in the Kyrle-Flegel lesion may arise from material contributed by these granules to the intercellular space.", "contents": "The permeability of epidermis lacking normal membrane-coating granules: an ultrastructural tracer study of Kyrle-Flegel disease. Skin lesions from patients with Flegel's disease have been reported to be without membrane-coating granules (Odland bodies). Biopsies of the hyperkeratinized papules of Kyrle-Flegel disease were incubated in vitro with the intercellular tracer, horseradish peroxidase, and the extent of penetration of this substance examined in the light and electron microscopes. The peroxidase was present throughout the corium and extended through the intercellular spaces of the epidermis to a level close to the junction of the granular and keratinized layers; it did not enter the bulk of the thickened stratum corneum of the lesion. Ultrastructural examination revealed the presence of small vesicles in the granular layer, similar in size and shape to membrane-coating granules but lacking a lamellate internal structure; these were occasionally seen fusing with the plasma membrane of the cells. It is suggested that the intercellular permeability barrier to horseradish peroxidase demonstrated in the Kyrle-Flegel lesion may arise from material contributed by these granules to the intercellular space."}
{"id": "PMID:206630", "title": "Infections with viruses and Mycoplasma pneumoniae during exacerbations of chronic bronchitis.", "content": "The association of viral and Mycoplasma pneumoniae infections with acute exacerbations of chronic bronchitis was studied by serologic or isolation techniques in 46 adult men during the five years from 1964 through 1968. Serologic evidence of viral or M. pneumoniae infection was detected in 25% of 166 episodes of exacerbation and 14% of 138 remission periods (P = 0.02). Influenza A virus, parainfluenza virus type 3, and coronavirus OC43 predominated; infections with other viruses were infrequent. Infection with M. pneumoniae was detected serologically in four patients, but this organism was never isolated from sputum specimens. Rhinoviruses were isolated from frozen-stored sputum specimens in in 2.7% of the episodes of exacerbation and from 0.55% of the remission intervals (P not significant). These data suggest that although exacerbations of chronic bronchitis may be accompanied by viral and M. pneumoniae infections, patients with chronic bronchitis also acquire such infections without a worsening of their respiratory status.", "contents": "Infections with viruses and Mycoplasma pneumoniae during exacerbations of chronic bronchitis. The association of viral and Mycoplasma pneumoniae infections with acute exacerbations of chronic bronchitis was studied by serologic or isolation techniques in 46 adult men during the five years from 1964 through 1968. Serologic evidence of viral or M. pneumoniae infection was detected in 25% of 166 episodes of exacerbation and 14% of 138 remission periods (P = 0.02). Influenza A virus, parainfluenza virus type 3, and coronavirus OC43 predominated; infections with other viruses were infrequent. Infection with M. pneumoniae was detected serologically in four patients, but this organism was never isolated from sputum specimens. Rhinoviruses were isolated from frozen-stored sputum specimens in in 2.7% of the episodes of exacerbation and from 0.55% of the remission intervals (P not significant). These data suggest that although exacerbations of chronic bronchitis may be accompanied by viral and M. pneumoniae infections, patients with chronic bronchitis also acquire such infections without a worsening of their respiratory status."}
{"id": "PMID:206631", "title": "Human foamy virus: further characterization, seroepidemiology, and relationship to chimpanzee foamy viruses.", "content": "A foamy virus present in human nasopharyngeal carcinoma tissue was studied for a number of biological properties, including range of cellular susceptibility, growth curve, evolution of cytopathic effect in relation to cellular fusion and intracellular viral distribution, reverse transcriptase activity, and buoyant density. The virus was also studied immunologically and found to be closely related to the chimpanzee foamy viruses, particularly simian foamy virus type 6, with which it shares common antigens in complement-fixing, fluorescent, and neutralizing antibody tests. In view of this close immunological relationship and the failure to find antibody to the human isolate in sera from more than 250 humans, including 50 patients with nasopharyngeal carcinoma and Burkitt's lymphoma, it is suggested that the isolate is not a human representative of the foamy virus group but rather a variant strain of chimpanzee foamy virus.", "contents": "Human foamy virus: further characterization, seroepidemiology, and relationship to chimpanzee foamy viruses. A foamy virus present in human nasopharyngeal carcinoma tissue was studied for a number of biological properties, including range of cellular susceptibility, growth curve, evolution of cytopathic effect in relation to cellular fusion and intracellular viral distribution, reverse transcriptase activity, and buoyant density. The virus was also studied immunologically and found to be closely related to the chimpanzee foamy viruses, particularly simian foamy virus type 6, with which it shares common antigens in complement-fixing, fluorescent, and neutralizing antibody tests. In view of this close immunological relationship and the failure to find antibody to the human isolate in sera from more than 250 humans, including 50 patients with nasopharyngeal carcinoma and Burkitt's lymphoma, it is suggested that the isolate is not a human representative of the foamy virus group but rather a variant strain of chimpanzee foamy virus."}
{"id": "PMID:206632", "title": "Effect of treatment with exogenous interferon, polyriboinosinic-polyribocytidylic acid, or polyriboinosinic-polyribocytidylic acid-poly-L-lysine complex on Herpesvirus hominis infections in mice.", "content": "The effect of treatment with exogenous interferon was compared with those of two interferon inducers, polyriboinosinic-polyribocytidylic acid [poly(I) . poly(C)] and poly(I) . poly(C)-poly-L-lysine complex [poly(ICLC)], in three model Herpesvirus hominis type 2 infections of mice. After intraperitoneal inoculation of H. hominis type 2, all drugs significantly protected animals against death and increased the mean day of death when administered as late as 48 hr after viral inoculation. With intranasal inoculation of H. hominis type 2, pretreatment with poly (I) . poly (C) and poly (ICLC) increased the mean day of death; however, no drug prevented death. In mice inoculated intravaginally, local treatment with exogenous interferon or poly(I) . poly(C) appeared to reduce the mean titers of virus in genital secretions and resulted in earlier clearance of infection in some animals. Systemic treatment of genital H. hominis type 2 infections with all drugs resulted in significant numbers of infected animals surviving the infection, although the mean titers of virus in genital secretions were unchanged. Therapeutic efficacy varied depending on the route of viral inoculation.", "contents": "Effect of treatment with exogenous interferon, polyriboinosinic-polyribocytidylic acid, or polyriboinosinic-polyribocytidylic acid-poly-L-lysine complex on Herpesvirus hominis infections in mice. The effect of treatment with exogenous interferon was compared with those of two interferon inducers, polyriboinosinic-polyribocytidylic acid [poly(I) . poly(C)] and poly(I) . poly(C)-poly-L-lysine complex [poly(ICLC)], in three model Herpesvirus hominis type 2 infections of mice. After intraperitoneal inoculation of H. hominis type 2, all drugs significantly protected animals against death and increased the mean day of death when administered as late as 48 hr after viral inoculation. With intranasal inoculation of H. hominis type 2, pretreatment with poly (I) . poly (C) and poly (ICLC) increased the mean day of death; however, no drug prevented death. In mice inoculated intravaginally, local treatment with exogenous interferon or poly(I) . poly(C) appeared to reduce the mean titers of virus in genital secretions and resulted in earlier clearance of infection in some animals. Systemic treatment of genital H. hominis type 2 infections with all drugs resulted in significant numbers of infected animals surviving the infection, although the mean titers of virus in genital secretions were unchanged. Therapeutic efficacy varied depending on the route of viral inoculation."}
{"id": "PMID:206633", "title": "Enhanced killing of myeloperoxidase-coated bacteria in the myeloperoxidase-H2O2-Cl- system.", "content": "Bacteria preincubated with myeloperoxidase (MPO) are more readily killed upon the addition of H2O2 and Cl- than controls not subject to prior incubation. This effect was evidenced by decreased requirements of MPO and H2O2 (to approximately 33%) for equivalent bactericidal activity. MPO adsorbed onto the bacterial surface is not accessible to other competing substrates such as guaiacol and [1(-14)C] alanine. It appears that when MPO is adsorbed to the bacteria, it carries out a coupled reaction in which the activated chlorine directly attacks the bacterial cell surface.", "contents": "Enhanced killing of myeloperoxidase-coated bacteria in the myeloperoxidase-H2O2-Cl- system. Bacteria preincubated with myeloperoxidase (MPO) are more readily killed upon the addition of H2O2 and Cl- than controls not subject to prior incubation. This effect was evidenced by decreased requirements of MPO and H2O2 (to approximately 33%) for equivalent bactericidal activity. MPO adsorbed onto the bacterial surface is not accessible to other competing substrates such as guaiacol and [1(-14)C] alanine. It appears that when MPO is adsorbed to the bacteria, it carries out a coupled reaction in which the activated chlorine directly attacks the bacterial cell surface."}
{"id": "PMID:206638", "title": "Isolation and characterization of cells from rat adipose tissue developing into adipocytes.", "content": "To identify cells developing into adipocytes by accumulation of triglyceride, rat epididymal fat pad cells from small rats were exposed to (3)H-labeled chylomicron fatty acids in vivo and then liberated with collagenase. Tissue remnants were removed by filtration and mature fat cells by flotation. Aggregating cells were then removed by filtration through a 25- micro m nylon screen. Further purification of cells labeled in vivo was obtained by removing floating cells from those adhering to the bottom of a culture dish. The adhering cells multiplied to a confluent monolayer when cultured in Medium 199 containing serum, glucose, insulin, and a triglyceride emulsion. The cells then gradually enlarged due to granulation of the cytoplasm by a lipid-staining material. After about 2 weeks these granules had coalesced forming mature adipocytes of typical signet-ring appearance. Free adipocytes could then be recovered from the cultures by collagenase treatment. After about 2 weeks of culture these cells had the same size (about 30 micro m) as adipocytes recovered in the original collagenase preparation of the rat epididymal fat pad. They contained triglyceride lipase activity and incorporated glucose into triglycerides to the same extent as cells developed in vivo but had higher lipoprotein lipase activity. In vitro, heparin in a low concentration, prostaglandin E(1), isobutylmethylxanthine, and cholera toxin markedly promoted the development of these cells into adipocytes. This could be shown to occur almost completely indicating that this fraction of cells was homogeneous and consisted of cells with the capacity to form adipocytes. The duplication time was about 2 days and did not change with subculturing. Preadipocytes could be obtained by density gradient centrifugation, isolating triglyceride-containing cells either directly from the pad or after 3 days in culture. All of these cells developed into adipocytes as described above but did not multiply as readily. It was concluded that cells from the epididymal fat pad from small rats can be isolated in a homogenous fraction that develops in culture into cells of identical morphology and function as adipocytes formed in vivo. The differentiation of these cells into adipocytes may be manipulated in vitro.", "contents": "Isolation and characterization of cells from rat adipose tissue developing into adipocytes. To identify cells developing into adipocytes by accumulation of triglyceride, rat epididymal fat pad cells from small rats were exposed to (3)H-labeled chylomicron fatty acids in vivo and then liberated with collagenase. Tissue remnants were removed by filtration and mature fat cells by flotation. Aggregating cells were then removed by filtration through a 25- micro m nylon screen. Further purification of cells labeled in vivo was obtained by removing floating cells from those adhering to the bottom of a culture dish. The adhering cells multiplied to a confluent monolayer when cultured in Medium 199 containing serum, glucose, insulin, and a triglyceride emulsion. The cells then gradually enlarged due to granulation of the cytoplasm by a lipid-staining material. After about 2 weeks these granules had coalesced forming mature adipocytes of typical signet-ring appearance. Free adipocytes could then be recovered from the cultures by collagenase treatment. After about 2 weeks of culture these cells had the same size (about 30 micro m) as adipocytes recovered in the original collagenase preparation of the rat epididymal fat pad. They contained triglyceride lipase activity and incorporated glucose into triglycerides to the same extent as cells developed in vivo but had higher lipoprotein lipase activity. In vitro, heparin in a low concentration, prostaglandin E(1), isobutylmethylxanthine, and cholera toxin markedly promoted the development of these cells into adipocytes. This could be shown to occur almost completely indicating that this fraction of cells was homogeneous and consisted of cells with the capacity to form adipocytes. The duplication time was about 2 days and did not change with subculturing. Preadipocytes could be obtained by density gradient centrifugation, isolating triglyceride-containing cells either directly from the pad or after 3 days in culture. All of these cells developed into adipocytes as described above but did not multiply as readily. It was concluded that cells from the epididymal fat pad from small rats can be isolated in a homogenous fraction that develops in culture into cells of identical morphology and function as adipocytes formed in vivo. The differentiation of these cells into adipocytes may be manipulated in vitro."}
{"id": "PMID:206639", "title": "Metabolic heterogeneity in the formation of low density lipoprotein from very low density lipoprotein in the rat: evidence for the independent production of a low density lipoprotein subfraction.", "content": "The formation of low density lipoprotein (LDL) from very low density lipoprotein (VLDL) was studied after injecting 14C-radiomethylated or 125I-radioiodinated VLDL into rats. VLDL and LDL B apoprotein specific radioactivity time curves were obtained after tetramethylurea extraction of the lipoproteins. In all experiments, the specific activity of LDL B apoprotein did not intercept the VLDL curve at maximal heights, suggesting that not all LDL B apoprotein is derived from VLDL B apoprotein. Further subfractionation of LDL into the Sf 12-20, 5-12, and 0-5 ranges showed that most (65%) LDL B apoprotein was present in the Sf 0-5 fraction and that only a small proportion (6-15%) of this fraction was derived from VLDL. However, the curves obtained for the Sf 12-20 and 5-12 subfractions were consistent with a precursor-product relationship in which all of these fractions were derived entirely from VLDL catabolism. These results contrasted strikingly with similar data obtained for normal humans in which all LDL is derived from VLDL. In the rat, it appears that most of the B apoprotein in the Sf 0-5 range, which contains 65% of the total LDL B apoprotein, enters the plasma independently of VLDL secretion.", "contents": "Metabolic heterogeneity in the formation of low density lipoprotein from very low density lipoprotein in the rat: evidence for the independent production of a low density lipoprotein subfraction. The formation of low density lipoprotein (LDL) from very low density lipoprotein (VLDL) was studied after injecting 14C-radiomethylated or 125I-radioiodinated VLDL into rats. VLDL and LDL B apoprotein specific radioactivity time curves were obtained after tetramethylurea extraction of the lipoproteins. In all experiments, the specific activity of LDL B apoprotein did not intercept the VLDL curve at maximal heights, suggesting that not all LDL B apoprotein is derived from VLDL B apoprotein. Further subfractionation of LDL into the Sf 12-20, 5-12, and 0-5 ranges showed that most (65%) LDL B apoprotein was present in the Sf 0-5 fraction and that only a small proportion (6-15%) of this fraction was derived from VLDL. However, the curves obtained for the Sf 12-20 and 5-12 subfractions were consistent with a precursor-product relationship in which all of these fractions were derived entirely from VLDL catabolism. These results contrasted strikingly with similar data obtained for normal humans in which all LDL is derived from VLDL. In the rat, it appears that most of the B apoprotein in the Sf 0-5 range, which contains 65% of the total LDL B apoprotein, enters the plasma independently of VLDL secretion."}
{"id": "PMID:206640", "title": "Stimulation of esterified cholesterol accumulation in tissue culture cells exposed to high density lipoproteins enriched in free cholesterol.", "content": "Human high density lipoprotein enriched in free cholesterol was obtained by exposing the lipoprotein to lipid dispersions having a free cholesterol/lecithin molar ratio greater than two. The metabolism of cholesterol was studied in tissue culture cells exposed to normal and cholesterol-enriched lipoproteins. Incubation of Fu5-AH rat hepatoma cells in medium containing cholesterol-enriched lipoprotein resulted in the accumulation of cellular cholesterol whereas normal high density lipoprotein produced no change in cellular content. The accumulated sterol was recovered primarily as esterified cholesterol and was derived almost entirely from lipoprotein free cholesterol. The esterification of incorporated free cholesterol and the cellular cholesterol content were directly related to the molar ratio of free cholesterol to phospholipid in the lipoprotein and to the concentration of lipoprotein in the culture medium. Isotopic experiments utilizing lipoprotein labeled with 125I or [4-14C]cholesteryl oleate demonstrated that a large fraction of the cholesterol incorporated from lipoprotein enriched in free cholesterol occurred by mechanisms that did not result in lipoprotein internalization and degradation. The response of other tissue culture cells to cholesterol/phospholipid dispersions is presented. The data indicate that the lipid composition of a lipoprotein can regulate free cholesterol uptake and esterification as well as cellular cholesterol content.", "contents": "Stimulation of esterified cholesterol accumulation in tissue culture cells exposed to high density lipoproteins enriched in free cholesterol. Human high density lipoprotein enriched in free cholesterol was obtained by exposing the lipoprotein to lipid dispersions having a free cholesterol/lecithin molar ratio greater than two. The metabolism of cholesterol was studied in tissue culture cells exposed to normal and cholesterol-enriched lipoproteins. Incubation of Fu5-AH rat hepatoma cells in medium containing cholesterol-enriched lipoprotein resulted in the accumulation of cellular cholesterol whereas normal high density lipoprotein produced no change in cellular content. The accumulated sterol was recovered primarily as esterified cholesterol and was derived almost entirely from lipoprotein free cholesterol. The esterification of incorporated free cholesterol and the cellular cholesterol content were directly related to the molar ratio of free cholesterol to phospholipid in the lipoprotein and to the concentration of lipoprotein in the culture medium. Isotopic experiments utilizing lipoprotein labeled with 125I or [4-14C]cholesteryl oleate demonstrated that a large fraction of the cholesterol incorporated from lipoprotein enriched in free cholesterol occurred by mechanisms that did not result in lipoprotein internalization and degradation. The response of other tissue culture cells to cholesterol/phospholipid dispersions is presented. The data indicate that the lipid composition of a lipoprotein can regulate free cholesterol uptake and esterification as well as cellular cholesterol content."}
{"id": "PMID:206641", "title": "Dynamic properties of human high density lipoprotein apoproteins.", "content": "This study was designed to identify a method for the measurement of human high density lipoprotein subfraction (HDL2 and HDL3) metabolism. Apolipoproteins A-I, A-II, and C, the major HDL apoproteins, were radioiodinated and incorporated individually into HDL2 and HDL3 in vitro. Using a double label technique, the turnover of apoA-I in HDL2 and HDL3 was measured simultaneously in a normal male. The apoprotein exchanged rapidly between the two subfractions, evidenced by equilibration of their apoA-I specific activity. Radiolabeled apoA-II, incorporated into the subfractions, showed a similar exchange in vitro. Incubation of 131I-labeled very low density lipoproteins (VLDL) with HDL or its subfractions resulted in transfer of C proteins from VLDL to the HDL moiety. The extent of transfer was dependent on the HDL subfraction present; 50% of the VLDL apoC was transferred to HDL3, while the transfer to total HDL and HDL2 was 69% and 78%, respectively. ApoC also exchanged between HDL2 and HDL3, again showing a preference for the former and suggesting a primary metabolic relationship between VLDL and HDL2. Overall, the study indicates that apoA-I, apoA-II, and the C proteins exist in equilibrium between HDL2 and HDL3. This phenomenon precludes their use as probes for HDL subfraction metabolism in humans.", "contents": "Dynamic properties of human high density lipoprotein apoproteins. This study was designed to identify a method for the measurement of human high density lipoprotein subfraction (HDL2 and HDL3) metabolism. Apolipoproteins A-I, A-II, and C, the major HDL apoproteins, were radioiodinated and incorporated individually into HDL2 and HDL3 in vitro. Using a double label technique, the turnover of apoA-I in HDL2 and HDL3 was measured simultaneously in a normal male. The apoprotein exchanged rapidly between the two subfractions, evidenced by equilibration of their apoA-I specific activity. Radiolabeled apoA-II, incorporated into the subfractions, showed a similar exchange in vitro. Incubation of 131I-labeled very low density lipoproteins (VLDL) with HDL or its subfractions resulted in transfer of C proteins from VLDL to the HDL moiety. The extent of transfer was dependent on the HDL subfraction present; 50% of the VLDL apoC was transferred to HDL3, while the transfer to total HDL and HDL2 was 69% and 78%, respectively. ApoC also exchanged between HDL2 and HDL3, again showing a preference for the former and suggesting a primary metabolic relationship between VLDL and HDL2. Overall, the study indicates that apoA-I, apoA-II, and the C proteins exist in equilibrium between HDL2 and HDL3. This phenomenon precludes their use as probes for HDL subfraction metabolism in humans."}
{"id": "PMID:206642", "title": "Crystalline inclusion bodies in rabbit embryos.", "content": "Crystalline inclusion bodies (CIB) may be found as prominent ultrastructural components of the trophoblast cells of rabbit blastocysts and of progestational uterine endometrium. In the work reported here we have sought to describe developmental steps in crystal formation, to correlate these events with embryonic age and to determine if the uterus is essential (either as a source or an environment) for crystal formation in the embryo. CIB, which are of a size and periodicity to make them appear to be clusters or packages of microtubules, are first detectable in embryos 4 days 6 h post coitum and by 41/2 days are well established in significant numbers. Another structural component, granular vesicles, may be seen in embryos as early as 21/2 days post coitum, and decrease in number during the same time the CIB are increasing. We believe that the CIB originate from the pre-existing granular vesicles and present electron micrograph evidence of crystal formation progressing from such vesicles. CIB formation does not occur in 41/2- to 5-day-old embryos which have been locked in the oviduct by a suture around the utero-tubal junction. However, when such tube-locked embryos are transplanted into the uterus, they develop crystals within 36 h thereafter. We conclude that the uterus is essential for CIB formation to occur in the rabbit embryo.", "contents": "Crystalline inclusion bodies in rabbit embryos. Crystalline inclusion bodies (CIB) may be found as prominent ultrastructural components of the trophoblast cells of rabbit blastocysts and of progestational uterine endometrium. In the work reported here we have sought to describe developmental steps in crystal formation, to correlate these events with embryonic age and to determine if the uterus is essential (either as a source or an environment) for crystal formation in the embryo. CIB, which are of a size and periodicity to make them appear to be clusters or packages of microtubules, are first detectable in embryos 4 days 6 h post coitum and by 41/2 days are well established in significant numbers. Another structural component, granular vesicles, may be seen in embryos as early as 21/2 days post coitum, and decrease in number during the same time the CIB are increasing. We believe that the CIB originate from the pre-existing granular vesicles and present electron micrograph evidence of crystal formation progressing from such vesicles. CIB formation does not occur in 41/2- to 5-day-old embryos which have been locked in the oviduct by a suture around the utero-tubal junction. However, when such tube-locked embryos are transplanted into the uterus, they develop crystals within 36 h thereafter. We conclude that the uterus is essential for CIB formation to occur in the rabbit embryo."}
{"id": "PMID:206643", "title": "Lymphocytes transformed by Epstein-Barr virus. Induction of nuclear antigen reactive with antibody in rheumatoid arthritis.", "content": "Sera from approximately two-thirds of patients with rheumatoid arthritis contain an antibody which is reactive with a nuclear antigen present in human B-lymphocyte tissue culture cells. The immunological reaction can be demonstrated by precipitation and immunofluorescence. Evidence is present that the reactive nuclear antigen is associated with Epstein-Barr (EB) virus-transformed lymphocytes. Normal human peripheral blood lymphocytes did not contain the nuclear antigen reactive with rheumatoid arthritis sera, but after infection with EB virus, they showed increasing amounts of reactive nuclear antigen as the cells were transformed into continuous lines. Several established human and simian lymphocyte cell lines known to carry EB viral genomes were shown to contain rheumatoid arthritis-associated nuclear antigen. Evidence is presented which suggests that the rheumatoid arthritis-associated nuclear antigen is different from the previously described EB nuclear antigen.", "contents": "Lymphocytes transformed by Epstein-Barr virus. Induction of nuclear antigen reactive with antibody in rheumatoid arthritis. Sera from approximately two-thirds of patients with rheumatoid arthritis contain an antibody which is reactive with a nuclear antigen present in human B-lymphocyte tissue culture cells. The immunological reaction can be demonstrated by precipitation and immunofluorescence. Evidence is present that the reactive nuclear antigen is associated with Epstein-Barr (EB) virus-transformed lymphocytes. Normal human peripheral blood lymphocytes did not contain the nuclear antigen reactive with rheumatoid arthritis sera, but after infection with EB virus, they showed increasing amounts of reactive nuclear antigen as the cells were transformed into continuous lines. Several established human and simian lymphocyte cell lines known to carry EB viral genomes were shown to contain rheumatoid arthritis-associated nuclear antigen. Evidence is presented which suggests that the rheumatoid arthritis-associated nuclear antigen is different from the previously described EB nuclear antigen."}
{"id": "PMID:206644", "title": "Effect of pseudotype on Abelson virus and Kirsten sarcoma virus-induced leukemia.", "content": "Nonproducer cells transformed by Kirsten sarcoma virus (KiSV) or Abelson murine leukemia virus (A-MuLV) were infected with N- or NB-tropic helper viruses to rescue the defective transforming virus. The titer of the transforming viruses was determined on NIH/3T3 fibroblast-like cells and cell-free filtrates of virus stock were inoculated into newborn Fv-1nn mice. Friend, Moloney, and Rauscher group of MuLV (FMR) pseudotypes of KiSV induced an erythroid leukemia efficiently, while an endogenous helper (N35-MuLV) pseudotype of KiSV did not. FMR pseudotypes of A-MuLV induced the Abelson lymphoid leukemia, while the N35-MuLV or a Kirsten leukemia virus (Ki-MuLV) pseudotype did not. Pseudotypes of A-MuLV were used to infect bone marrow cells of Fv-1nn mice in vitro. The FMR pseudotypes transformed bone marrow cells at 40-100-fold higher frequency than the N35-MuLV or Ki-MuLV pseudotypes. Mixing experiments demonstrated that the addition of an effective helper, such as M-MuLV did not enhance lymphoid transformation by ineffective A-MuLV (N35-MuLV). The A-MuLV genome is responsible for hematopoietic cell transformation because a nonproducer clone of lymphoid cells, free of helper virus, was isolated. The data indicates that the pseudotype of A-MuLV determines its ability to transform hematopoietic cells.", "contents": "Effect of pseudotype on Abelson virus and Kirsten sarcoma virus-induced leukemia. Nonproducer cells transformed by Kirsten sarcoma virus (KiSV) or Abelson murine leukemia virus (A-MuLV) were infected with N- or NB-tropic helper viruses to rescue the defective transforming virus. The titer of the transforming viruses was determined on NIH/3T3 fibroblast-like cells and cell-free filtrates of virus stock were inoculated into newborn Fv-1nn mice. Friend, Moloney, and Rauscher group of MuLV (FMR) pseudotypes of KiSV induced an erythroid leukemia efficiently, while an endogenous helper (N35-MuLV) pseudotype of KiSV did not. FMR pseudotypes of A-MuLV induced the Abelson lymphoid leukemia, while the N35-MuLV or a Kirsten leukemia virus (Ki-MuLV) pseudotype did not. Pseudotypes of A-MuLV were used to infect bone marrow cells of Fv-1nn mice in vitro. The FMR pseudotypes transformed bone marrow cells at 40-100-fold higher frequency than the N35-MuLV or Ki-MuLV pseudotypes. Mixing experiments demonstrated that the addition of an effective helper, such as M-MuLV did not enhance lymphoid transformation by ineffective A-MuLV (N35-MuLV). The A-MuLV genome is responsible for hematopoietic cell transformation because a nonproducer clone of lymphoid cells, free of helper virus, was isolated. The data indicates that the pseudotype of A-MuLV determines its ability to transform hematopoietic cells."}
{"id": "PMID:206645", "title": "G(RADA1): a new cell surface antigen of mouse leukemia defined by naturally occurring antibody and its relationship to murine leukemia virus.", "content": "A new cell surface antigenic system of the mouse, designated G(RADA1), is described. The antigen is defined by cytotoxic tests with the A strain X-ray-induced leukemia RADA1 and naturally occurring antibody from random-bred Swiss mice and can be distinguished from all other serologically detected cell surface antigens of the mouse. Absorption tests indicate that G(RADA1) is present in the normal lymphatic tissue and leukemias of mouse strains with high spontaneous leukemia-incidence, e.g., AKR, C58, and C3H/Figge. Low leukemia-incidence strains, e.g., C57BL/6, BALB/c, and A lack G(RADA1) in their normal tissues, but a proportion of leukemias and solid tumors arising in these strains are G(RADA1)+. The relation of G(RADA1) to MuLV is shown by G(RADA1) appearance after MuLV infection of permissive cells in vitro; four of five N-tropic MuLV isolates, one of four B-tropic MuLV, and none of four xenotropic MuLV induce G(RADA1). Two MCF MuLV, thought to represent recombinants between N-ecotropic and xenotropic MuLV, also induce G(RADA1). Serological and biochemical characterization indicates that G(RADA1) is a type-specific determinant of the gp70 component of certain MuLV. The presence of natural antibody to RADA1 in various mouse strains and the emergence of G(RADA1)+ leukemias and solid tumors in mice of G(RADA1)- phenotype suggest widespread occurrence of genetic information coding for this antigen.", "contents": "G(RADA1): a new cell surface antigen of mouse leukemia defined by naturally occurring antibody and its relationship to murine leukemia virus. A new cell surface antigenic system of the mouse, designated G(RADA1), is described. The antigen is defined by cytotoxic tests with the A strain X-ray-induced leukemia RADA1 and naturally occurring antibody from random-bred Swiss mice and can be distinguished from all other serologically detected cell surface antigens of the mouse. Absorption tests indicate that G(RADA1) is present in the normal lymphatic tissue and leukemias of mouse strains with high spontaneous leukemia-incidence, e.g., AKR, C58, and C3H/Figge. Low leukemia-incidence strains, e.g., C57BL/6, BALB/c, and A lack G(RADA1) in their normal tissues, but a proportion of leukemias and solid tumors arising in these strains are G(RADA1)+. The relation of G(RADA1) to MuLV is shown by G(RADA1) appearance after MuLV infection of permissive cells in vitro; four of five N-tropic MuLV isolates, one of four B-tropic MuLV, and none of four xenotropic MuLV induce G(RADA1). Two MCF MuLV, thought to represent recombinants between N-ecotropic and xenotropic MuLV, also induce G(RADA1). Serological and biochemical characterization indicates that G(RADA1) is a type-specific determinant of the gp70 component of certain MuLV. The presence of natural antibody to RADA1 in various mouse strains and the emergence of G(RADA1)+ leukemias and solid tumors in mice of G(RADA1)- phenotype suggest widespread occurrence of genetic information coding for this antigen."}
{"id": "PMID:206646", "title": "The effect of helper virus on Abelson virus-induced transformation of lymphoid cells.", "content": "Abelson murine leukemia virus (A-MuLV)-transformed fibroblast nonproducer cells were used to prepare A-MuLV stocks containing a number of different helper viruses. The oncogenicity of the A-MuLV stocks was tested by animal inoculation and their ability to transform normal mouse bone marrow cells was measured in vitro. All of the A-MuLV stocks transformed fibroblast cells efficiently. However, only A-MuLV stocks prepared with helper viruses that are highly oncogenic were efficient in vivo and in vitro in hematopoietic cell transformation. In addition, inefficient helpers did not establish a stable infection in lymphoid nonproducer cells. Thus, helper virus has a more central role in lymphoid cell transformation than in fibroblast cell transformation.", "contents": "The effect of helper virus on Abelson virus-induced transformation of lymphoid cells. Abelson murine leukemia virus (A-MuLV)-transformed fibroblast nonproducer cells were used to prepare A-MuLV stocks containing a number of different helper viruses. The oncogenicity of the A-MuLV stocks was tested by animal inoculation and their ability to transform normal mouse bone marrow cells was measured in vitro. All of the A-MuLV stocks transformed fibroblast cells efficiently. However, only A-MuLV stocks prepared with helper viruses that are highly oncogenic were efficient in vivo and in vitro in hematopoietic cell transformation. In addition, inefficient helpers did not establish a stable infection in lymphoid nonproducer cells. Thus, helper virus has a more central role in lymphoid cell transformation than in fibroblast cell transformation."}
{"id": "PMID:206647", "title": "Relationships of gp70 of MuLV envelopes to gp70 components of mouse lymphocyte plasma membranes.", "content": "The family of glycoproteins called gp70 includes molecules that are the main constituent of murine C-type viral envelopes, and some that are expressed as mendelian constituents of thymocyte plasma membranes in the absence of virions. To investigate further the relation of viral gp70s to plasma- membrane gp70s we compared peptide maps of gp70s derived by immunoprecipitation from cells infected with chosen viruses and from various thymocytes and leukemiacells known to express one or more of three immunogenetically defined gp70 types: Glx-gp70, X-gp70, and O-gp70. Maps of gp70 from cultured cells infected with ecotropic and xenotropic viruses were distinguishable from one another, and in general resembled gp70 maps prepared directly from ecotropic and xenotropic virions respectively. Maps of gp70s immunoprecipitated from thymocytes of five mouse strains and from two A strain T-cell leukemias also fell into two distinguishable and generally corresponding patterns. Thus peptide-mapping substantiates earlier conclusions that viral gp70s and plasma-membrane gp70s inherited independently of virus-production are highly related or identical molecules. The gp70 maps of thymocytes from B6, B6-G(+IX), 129, and A mice formed a group resembling the map from cultured cells infected with xenotropic virus. Thymocytes from AKR mice, and the two A strain leukemias, gave gp70 maps conforming more to the second pattern, that of cultured cells infected with ecotropic virus. This second pattern probably comprises at least two gp70 types, one of which is X-gp70. Our data indicate that the G(IX)-gp70 and O-gp70 sub-species of gp70 expressed in the cell populations we have studied are coded by xenotropic viral genomes, and X-gp70 by ecotropic viral genomes.", "contents": "Relationships of gp70 of MuLV envelopes to gp70 components of mouse lymphocyte plasma membranes. The family of glycoproteins called gp70 includes molecules that are the main constituent of murine C-type viral envelopes, and some that are expressed as mendelian constituents of thymocyte plasma membranes in the absence of virions. To investigate further the relation of viral gp70s to plasma- membrane gp70s we compared peptide maps of gp70s derived by immunoprecipitation from cells infected with chosen viruses and from various thymocytes and leukemiacells known to express one or more of three immunogenetically defined gp70 types: Glx-gp70, X-gp70, and O-gp70. Maps of gp70 from cultured cells infected with ecotropic and xenotropic viruses were distinguishable from one another, and in general resembled gp70 maps prepared directly from ecotropic and xenotropic virions respectively. Maps of gp70s immunoprecipitated from thymocytes of five mouse strains and from two A strain T-cell leukemias also fell into two distinguishable and generally corresponding patterns. Thus peptide-mapping substantiates earlier conclusions that viral gp70s and plasma-membrane gp70s inherited independently of virus-production are highly related or identical molecules. The gp70 maps of thymocytes from B6, B6-G(+IX), 129, and A mice formed a group resembling the map from cultured cells infected with xenotropic virus. Thymocytes from AKR mice, and the two A strain leukemias, gave gp70 maps conforming more to the second pattern, that of cultured cells infected with ecotropic virus. This second pattern probably comprises at least two gp70 types, one of which is X-gp70. Our data indicate that the G(IX)-gp70 and O-gp70 sub-species of gp70 expressed in the cell populations we have studied are coded by xenotropic viral genomes, and X-gp70 by ecotropic viral genomes."}
{"id": "PMID:206648", "title": "Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis.", "content": "An acute phase of experimental autoimmune myasthenia gravis (EAMG) occurs transiently early in the immune response of Lewis rats to nicotinic acetylcholine receptors (AChR) when Bordetella pertussis is used as adjuvant. It is characterized by a destructive cellular attack directed at the postsynaptic membranes of muscle. Acute EAMG can be passively transferred to normal rats by IgG from serum of rats with chronic EAMG. In the present study, acute EAMG, induced either by passive transfer of syngeneic antibodies or by active immmunization, was inhibited in rats depleted of complement by treatment with cobra venom factor (CoF). Furthermore, passive transfer of antibodies in excess of the muscle's content of AChR was without any measurable effect in rats treated with CoF. Although 60% of the muscle's AChR was complexed with antibody, there was no reduction in the muscle's content of AChR, and neuromuscular transmission was not compromised as judged electromyographically by curare sensitivity. These data imply that redistribution, accelerated degradation, and impairment of the ionophore function of AChR, effects of antibodies described in vitro on extrajunctional AChR, do not play a significant role in vivo in impairing neuromuscular transmission in an intact neuromuscular junction. Complement appears to be a critical mediator of anti-AChR antibodies' pathogenicity in vivo.", "contents": "Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis. An acute phase of experimental autoimmune myasthenia gravis (EAMG) occurs transiently early in the immune response of Lewis rats to nicotinic acetylcholine receptors (AChR) when Bordetella pertussis is used as adjuvant. It is characterized by a destructive cellular attack directed at the postsynaptic membranes of muscle. Acute EAMG can be passively transferred to normal rats by IgG from serum of rats with chronic EAMG. In the present study, acute EAMG, induced either by passive transfer of syngeneic antibodies or by active immmunization, was inhibited in rats depleted of complement by treatment with cobra venom factor (CoF). Furthermore, passive transfer of antibodies in excess of the muscle's content of AChR was without any measurable effect in rats treated with CoF. Although 60% of the muscle's AChR was complexed with antibody, there was no reduction in the muscle's content of AChR, and neuromuscular transmission was not compromised as judged electromyographically by curare sensitivity. These data imply that redistribution, accelerated degradation, and impairment of the ionophore function of AChR, effects of antibodies described in vitro on extrajunctional AChR, do not play a significant role in vivo in impairing neuromuscular transmission in an intact neuromuscular junction. Complement appears to be a critical mediator of anti-AChR antibodies' pathogenicity in vivo."}
{"id": "PMID:206649", "title": "Sensitization of lymphocytes against pooled allogeneic cells. I. Generation of cytotoxicity against autologous human lymphoblastoid cell lines.", "content": "Lymphocytes sensitized in vitro to a pool of X-irradiated allogeneic normal lymphocytes from 20 individuals develop cytotoxic activity for autologous human lymphoblastoid cells (LCL). Whereas pool sensitized T lymphocytes lyse autologous LCL cells, they fail to lyse autologous B-enriched or T-enriched normal target cells nor autologous phytohemagglutinin (PHA) blasts. In contrast to pool sensitization, stimulation with normal cells of single allogeneic individuals rarely led to development of cytotoxicity against autologous LCL cells. We conclude that human Epstein-Barr virus transformed LCL cells express target antigens cross-reactive with allogeneic target antigens expressed on normal cells and that sensitization with a pool of allogeneic cells is an effective means of generating effector cells directed against autologous abnormal cells.", "contents": "Sensitization of lymphocytes against pooled allogeneic cells. I. Generation of cytotoxicity against autologous human lymphoblastoid cell lines. Lymphocytes sensitized in vitro to a pool of X-irradiated allogeneic normal lymphocytes from 20 individuals develop cytotoxic activity for autologous human lymphoblastoid cells (LCL). Whereas pool sensitized T lymphocytes lyse autologous LCL cells, they fail to lyse autologous B-enriched or T-enriched normal target cells nor autologous phytohemagglutinin (PHA) blasts. In contrast to pool sensitization, stimulation with normal cells of single allogeneic individuals rarely led to development of cytotoxicity against autologous LCL cells. We conclude that human Epstein-Barr virus transformed LCL cells express target antigens cross-reactive with allogeneic target antigens expressed on normal cells and that sensitization with a pool of allogeneic cells is an effective means of generating effector cells directed against autologous abnormal cells."}
{"id": "PMID:206651", "title": "The chromosomal location and pleiotropic effects of mutations of the nirA+ gene of Escherichia coli K12: the essential role of nirA+ in nitrite reduction and in other anaerobic redox reactions.", "content": "Cytochrome c552, which has been implicated as an electron carrier for nitrite reduction by Escherichia coli, has been separated from NADH-nitrite oxidoreductase activity. The cytochrome is therefore not required for the reduction of nitrite by NADH in vitro. Nevertheless, some mutants which were selected by their inability to use nitrite as a nitrogen source during anaerobic growth synthesize neither NADH-nitrite oxidoreductase nor cytochrome c552. The defects in these mutants are due to mutations in a single gene, nirA, which is located at about minute 29 on the recalibrated linkage map. Experiments with an F' plasmid which carries a nirA+ allele established that nirA+ is dominant to the defective allele. Other mutants, defective in nitrate reductase activity because of mutations in the chlA or chlB genes, synthesized nitrite reductase and cytochrome c552 in the absence of nitrate or nitrite. A mutant with a defective fnr gene was also NirA- and, conversely, nirA mutants were Fnr-. In a series of transduction experiments, attempts to separate the nirA and fnr defects were unsuccessful. Furthermore, no complementation was observed when an F' plasmid carrying a defective nirA allele was transferred into the fnr strain. It is concluded that the fnr gene described by Lambden & Guest (1976) is identical to the nirA gene and that its product affects the synthesis or assembly of a variety of anaerobic redox enzymes which include nitrite reductase, cytochrome c552, nitrate reductase, fumarate reductase and formate hydrogenlyase.", "contents": "The chromosomal location and pleiotropic effects of mutations of the nirA+ gene of Escherichia coli K12: the essential role of nirA+ in nitrite reduction and in other anaerobic redox reactions. Cytochrome c552, which has been implicated as an electron carrier for nitrite reduction by Escherichia coli, has been separated from NADH-nitrite oxidoreductase activity. The cytochrome is therefore not required for the reduction of nitrite by NADH in vitro. Nevertheless, some mutants which were selected by their inability to use nitrite as a nitrogen source during anaerobic growth synthesize neither NADH-nitrite oxidoreductase nor cytochrome c552. The defects in these mutants are due to mutations in a single gene, nirA, which is located at about minute 29 on the recalibrated linkage map. Experiments with an F' plasmid which carries a nirA+ allele established that nirA+ is dominant to the defective allele. Other mutants, defective in nitrate reductase activity because of mutations in the chlA or chlB genes, synthesized nitrite reductase and cytochrome c552 in the absence of nitrate or nitrite. A mutant with a defective fnr gene was also NirA- and, conversely, nirA mutants were Fnr-. In a series of transduction experiments, attempts to separate the nirA and fnr defects were unsuccessful. Furthermore, no complementation was observed when an F' plasmid carrying a defective nirA allele was transferred into the fnr strain. It is concluded that the fnr gene described by Lambden & Guest (1976) is identical to the nirA gene and that its product affects the synthesis or assembly of a variety of anaerobic redox enzymes which include nitrite reductase, cytochrome c552, nitrate reductase, fumarate reductase and formate hydrogenlyase."}
{"id": "PMID:206652", "title": "Purification and properties of the arginine-specific carbamoyl-phosphate synthase from Saccharomyces cerevisiae.", "content": "The arginine-specific carbamoyl-phosphate synthase of yeast was stabilized sufficiently to allow partial purification of the enzyme (30- to 40-fold). The synthase (mol. wt 115000) comprised two unequal subunits: a heavy subunit (mol. wt 80000) capable of catalysing synthesis of carbamoyl phosphate with ammonia as a nitrogen donor and a light subunit conferring upon the holoenzyme the ability to utilize glutamine. The enzyme had unusually high affinity for ATP (Km = 0.2 mM) and atypical negative cooperativity for glutamine binding ([S]0.5 = 0.25 mM). Glutamine activity was not modulated by possible effectors such as arginine, ornithine or N-acetylglutamate. Thus, although the yeast arginine enzyme physically and functionally resembles the single enteric synthase, the systems differ substantially both in kinetic properties and in regulation of activity.", "contents": "Purification and properties of the arginine-specific carbamoyl-phosphate synthase from Saccharomyces cerevisiae. The arginine-specific carbamoyl-phosphate synthase of yeast was stabilized sufficiently to allow partial purification of the enzyme (30- to 40-fold). The synthase (mol. wt 115000) comprised two unequal subunits: a heavy subunit (mol. wt 80000) capable of catalysing synthesis of carbamoyl phosphate with ammonia as a nitrogen donor and a light subunit conferring upon the holoenzyme the ability to utilize glutamine. The enzyme had unusually high affinity for ATP (Km = 0.2 mM) and atypical negative cooperativity for glutamine binding ([S]0.5 = 0.25 mM). Glutamine activity was not modulated by possible effectors such as arginine, ornithine or N-acetylglutamate. Thus, although the yeast arginine enzyme physically and functionally resembles the single enteric synthase, the systems differ substantially both in kinetic properties and in regulation of activity."}
{"id": "PMID:206653", "title": "Morphogenesis of porcine rotavirus in porcine kidney cell cultures and intestinal epithelial cells.", "content": "The morphogenesis of porcine rotavirus was similar in vitro in porcine kidney (PK) cell cultures and in vivo in porcine epithelial cells as examined by electron microscopy. Infected cells contained cytoplasmic, non-membrane-bound viroplasm and accumulations of virus particles within cisternae of the rough endoplasmic reticulum (RER). Three types of virus particles were noted: double-shelled or complete particles which averaged 77 nm in diam.; single-shelled or naked particles which ranged from 50 to 55 nm in diam.; and electron-dense nucleoids, or cores, 31 to 38 nm in diam. Virus particles acquired outer shells by budding through either matrices of granular, electron-dense viroplasm or membranes of distended RER. Accumulation of numerous single-shelled particles was observed only in PK cell cultures containing a high percentage of infected cells. In these cells, virus release occurred through disruption of the plasma membrane. Tubules, similar in diameter to the single-shelled particles, were observed in the nuclei of a few infected PK cells.", "contents": "Morphogenesis of porcine rotavirus in porcine kidney cell cultures and intestinal epithelial cells. The morphogenesis of porcine rotavirus was similar in vitro in porcine kidney (PK) cell cultures and in vivo in porcine epithelial cells as examined by electron microscopy. Infected cells contained cytoplasmic, non-membrane-bound viroplasm and accumulations of virus particles within cisternae of the rough endoplasmic reticulum (RER). Three types of virus particles were noted: double-shelled or complete particles which averaged 77 nm in diam.; single-shelled or naked particles which ranged from 50 to 55 nm in diam.; and electron-dense nucleoids, or cores, 31 to 38 nm in diam. Virus particles acquired outer shells by budding through either matrices of granular, electron-dense viroplasm or membranes of distended RER. Accumulation of numerous single-shelled particles was observed only in PK cell cultures containing a high percentage of infected cells. In these cells, virus release occurred through disruption of the plasma membrane. Tubules, similar in diameter to the single-shelled particles, were observed in the nuclei of a few infected PK cells."}
{"id": "PMID:206654", "title": "Physical maps for HSV type 2 DNA with five restriction endonucleases.", "content": "The ordering of restriction endonuclease fragments of HSV-2 DNA for physical maps has been studied using molecular hybridization techniques and the cleavage of isolated restriction endonuclease fragments with further restriction endonucleases. Physical maps for the fragments produced by EcoRI, Hind III, Bgl II, Xba and Hpa I have been constructed. The mol. wt. of the various regions which constitute HSV-2 genome are very similar to the corresponding mol. wt. in the HSV-1 genome.", "contents": "Physical maps for HSV type 2 DNA with five restriction endonucleases. The ordering of restriction endonuclease fragments of HSV-2 DNA for physical maps has been studied using molecular hybridization techniques and the cleavage of isolated restriction endonuclease fragments with further restriction endonucleases. Physical maps for the fragments produced by EcoRI, Hind III, Bgl II, Xba and Hpa I have been constructed. The mol. wt. of the various regions which constitute HSV-2 genome are very similar to the corresponding mol. wt. in the HSV-1 genome."}
{"id": "PMID:206655", "title": "Host defence mechanisms against dengue virus infection of mice.", "content": "Serum obtained from mice 3 to 5 weeks after the third i.p. dose of dengue type 2 virus (DV) protected recipient mice against intracerebral challenge with DV, whereas the serum obtained after 1 and 2 weeks provided minimum protection. Adoptive intravenous transfer of immune spleen cells obtained from mice 1 to 5 weeks after immunization did not protect recipient mice against even a small dose (10 LD50) of DV. Depletion of T-cells by treatment of mice with anti-thymocyte serum did not potentiate DV infection. Development of a cell-mediated immune response (CMI) against DV was noted only at two periods by the leucocyte migration inhibition test (LMI), with borderline values of 20 and 21%. Dengue virus did not cause illness or death in mice when given by i.p. or i.v. routes and this was not affected by pre-treatment of mice with silica to damage local macrophages. It is concluded that humoral antibody plays a critical role in recovery from primary dengue virus infection of mice whereas CMI and macrophages appear to have no protective role.", "contents": "Host defence mechanisms against dengue virus infection of mice. Serum obtained from mice 3 to 5 weeks after the third i.p. dose of dengue type 2 virus (DV) protected recipient mice against intracerebral challenge with DV, whereas the serum obtained after 1 and 2 weeks provided minimum protection. Adoptive intravenous transfer of immune spleen cells obtained from mice 1 to 5 weeks after immunization did not protect recipient mice against even a small dose (10 LD50) of DV. Depletion of T-cells by treatment of mice with anti-thymocyte serum did not potentiate DV infection. Development of a cell-mediated immune response (CMI) against DV was noted only at two periods by the leucocyte migration inhibition test (LMI), with borderline values of 20 and 21%. Dengue virus did not cause illness or death in mice when given by i.p. or i.v. routes and this was not affected by pre-treatment of mice with silica to damage local macrophages. It is concluded that humoral antibody plays a critical role in recovery from primary dengue virus infection of mice whereas CMI and macrophages appear to have no protective role."}
{"id": "PMID:206656", "title": "Regulation of interferon production by dibutyryl cyclic GMP in serum-free human diploid cell cultures.", "content": "The mechanism for regulating interferon production was investigated in relation to accentuation of production in serum-free human diploid cells (strain WI-38) treated with N2,O2-dibutyryl guanosine 3',5'-cyclic monophosphate (db-cyclic GMP). Interferon production in serum-free WI-38 cell cultures in response to Newcastle disease virus (NDV) was greatly reduced. In these cells, there was decreased incorporation of 5-3H-uridine into the acid-insoluble fraction, but unimpaired incorporation of U-14C-L-leucine, as compared with serum-containing cultures. When serum-free cell cultures were treated with 0.2 mM-db-cyclic GMP, incorporation of both 5-3H-uridine and U-14C-L-leucine was increased and there was an 8-fold enhancement in the yield of interferon in response to NDV. Induction of db-cyclic GMP-treated cells by NDV in the presence of cycloheximide and actinomycin D suggests that db-cyclic GMP enhances transcription of the interferon gene, and thereby augments interferon production.", "contents": "Regulation of interferon production by dibutyryl cyclic GMP in serum-free human diploid cell cultures. The mechanism for regulating interferon production was investigated in relation to accentuation of production in serum-free human diploid cells (strain WI-38) treated with N2,O2-dibutyryl guanosine 3',5'-cyclic monophosphate (db-cyclic GMP). Interferon production in serum-free WI-38 cell cultures in response to Newcastle disease virus (NDV) was greatly reduced. In these cells, there was decreased incorporation of 5-3H-uridine into the acid-insoluble fraction, but unimpaired incorporation of U-14C-L-leucine, as compared with serum-containing cultures. When serum-free cell cultures were treated with 0.2 mM-db-cyclic GMP, incorporation of both 5-3H-uridine and U-14C-L-leucine was increased and there was an 8-fold enhancement in the yield of interferon in response to NDV. Induction of db-cyclic GMP-treated cells by NDV in the presence of cycloheximide and actinomycin D suggests that db-cyclic GMP enhances transcription of the interferon gene, and thereby augments interferon production."}
{"id": "PMID:206657", "title": "Controlled proteolytic digestion of the M-protein of Sendai virus: the isolation of a fragment of 30000 molecular weight.", "content": "Proteolytic digestion of the M-protein of Sendai virus produces a product with a mol. wt. approximately 5000 less than that of the intact protein. In the case of digestion with chymotrypsin this cleavage is quite specific and the cleaved protein can be isolated. The smaller fragment appears to be physically removed from the larger (30000 mol. wt.) fragment, rather than remaining in non-covalent association with it. The cleavage is likely to be near the N-terminus of the protein. At the present time there is no indication of the biological function of this fragment.", "contents": "Controlled proteolytic digestion of the M-protein of Sendai virus: the isolation of a fragment of 30000 molecular weight. Proteolytic digestion of the M-protein of Sendai virus produces a product with a mol. wt. approximately 5000 less than that of the intact protein. In the case of digestion with chymotrypsin this cleavage is quite specific and the cleaved protein can be isolated. The smaller fragment appears to be physically removed from the larger (30000 mol. wt.) fragment, rather than remaining in non-covalent association with it. The cleavage is likely to be near the N-terminus of the protein. At the present time there is no indication of the biological function of this fragment."}
{"id": "PMID:206658", "title": "Herpes simplex virus infection of in vitro cultured neuronal cells (mouse neuroblastoma C 1300 cells).", "content": "The nature of the restriction of herpes simplex virus replication in C 1300 neuroblastoma cells was studied. A low rate of adsorption was observed, probably due to the relatively few receptors for HSV on plasma membranes of C 1300 cells. The penetration rate of HSV to the nucleus was slow with an impaired processing of attached virus from plasma membrane to cell nucleus. Even at a high multiplicity of infection only a low percentage of the C 1300 neuroblastoma cells was permissively infected as determined by infectious centre assays. The yield of infectious HSV per virus-producing C 1300 cell was 1% of the yield from GMK control cells. The restriction in neuroblastoma cells of HSV infection could not be accounted for by sensitivity of cells to interferon or by an efficient induction of interferon. Evidence was obtained for the presence in C 1300 cells of an inhibitor of HSV replication not compatible with classical interferon. Observations on C 1300 cells maintaining many characteristics of differentiated neurons suggest that these cells may be useful as a model for studies on HSV-neuron interactions.", "contents": "Herpes simplex virus infection of in vitro cultured neuronal cells (mouse neuroblastoma C 1300 cells). The nature of the restriction of herpes simplex virus replication in C 1300 neuroblastoma cells was studied. A low rate of adsorption was observed, probably due to the relatively few receptors for HSV on plasma membranes of C 1300 cells. The penetration rate of HSV to the nucleus was slow with an impaired processing of attached virus from plasma membrane to cell nucleus. Even at a high multiplicity of infection only a low percentage of the C 1300 neuroblastoma cells was permissively infected as determined by infectious centre assays. The yield of infectious HSV per virus-producing C 1300 cell was 1% of the yield from GMK control cells. The restriction in neuroblastoma cells of HSV infection could not be accounted for by sensitivity of cells to interferon or by an efficient induction of interferon. Evidence was obtained for the presence in C 1300 cells of an inhibitor of HSV replication not compatible with classical interferon. Observations on C 1300 cells maintaining many characteristics of differentiated neurons suggest that these cells may be useful as a model for studies on HSV-neuron interactions."}
{"id": "PMID:206659", "title": "A host range difference between herpes simplex virus types 1 and 2.", "content": "The infectivities of several strains of herpes simplex virus type 1 and type 2 were measured by plating on established human and Chinese hamster cell lines. Whereas all the type 1 strains reproducibly showed a 10(4)-fold lower titre on the Chinese hamster cells, the type 2 strains showed only a 10- to 100-fold lower titre. This host range difference has been used in the analysis of recombinants between type 1 and type 2 viruses.", "contents": "A host range difference between herpes simplex virus types 1 and 2. The infectivities of several strains of herpes simplex virus type 1 and type 2 were measured by plating on established human and Chinese hamster cell lines. Whereas all the type 1 strains reproducibly showed a 10(4)-fold lower titre on the Chinese hamster cells, the type 2 strains showed only a 10- to 100-fold lower titre. This host range difference has been used in the analysis of recombinants between type 1 and type 2 viruses."}
{"id": "PMID:206660", "title": "The frequencies of transcription from the E- and L-strands of polyoma DNA.", "content": "Exhaustion type hybridization was used to measure the amount of nuclear virus RNA complementary to the early (E) and late (L) polyoma virus DNA strands. At 36 h after infection between 2.5 and 7.3% of the newly synthesized virus RNA was complementary to the E-strand (-strand) and between 92.7 and 97.5% was complementary to the L-strand (+strand). This proportion was independent of the labelling time, indicating similar accumulation of the E- and L-RNA transcripts in the nucleus. The nuclear E- and L-RNA transcripts sedimented in a similar manner through sucrose gradients.", "contents": "The frequencies of transcription from the E- and L-strands of polyoma DNA. Exhaustion type hybridization was used to measure the amount of nuclear virus RNA complementary to the early (E) and late (L) polyoma virus DNA strands. At 36 h after infection between 2.5 and 7.3% of the newly synthesized virus RNA was complementary to the E-strand (-strand) and between 92.7 and 97.5% was complementary to the L-strand (+strand). This proportion was independent of the labelling time, indicating similar accumulation of the E- and L-RNA transcripts in the nucleus. The nuclear E- and L-RNA transcripts sedimented in a similar manner through sucrose gradients."}
{"id": "PMID:206661", "title": "Interaction of ultraviolet-irradiated herpes simplex virus type 1 with BSC-1 cells.", "content": "Ultraviolet irradiation of herpes simplex virus (HSV) did not affect the transfer of uncoated virus DNA to the nuclei of infected cells but the synthesis of virus DNA was suppressed. The virus-specific DNA polymerase was synthesized in cells infected with the u.v.-irradiated HF strain of HSV. In cells infected with the u.v.-irradiated KOS strain, the virus DNA polymerase activity was hardly detectable. The two strains of HSV differ in the sensitivity of the virus DNA polymerase gene to u.v.-irradiation.", "contents": "Interaction of ultraviolet-irradiated herpes simplex virus type 1 with BSC-1 cells. Ultraviolet irradiation of herpes simplex virus (HSV) did not affect the transfer of uncoated virus DNA to the nuclei of infected cells but the synthesis of virus DNA was suppressed. The virus-specific DNA polymerase was synthesized in cells infected with the u.v.-irradiated HF strain of HSV. In cells infected with the u.v.-irradiated KOS strain, the virus DNA polymerase activity was hardly detectable. The two strains of HSV differ in the sensitivity of the virus DNA polymerase gene to u.v.-irradiation."}
{"id": "PMID:206662", "title": "Chromic-acid formaldehyde fixation of nucleic acids of bacteriophage phi6 and infectious bovine rhinotracheitis virus.", "content": "Bacteriophage phi6 nucleic acid was present as a torus after chromic acid-formaldehyde-OSO4 fixation and acetone and propylene oxide dehydration. A herpes virus, infectious bovine rhinotracheitis virus, had its DNA mostly as a torus, collapsed in the centre, or as a network, after glutaraldehyde-OSO4 fixation, but in an uncollapsed torus or network formation after chromic acid-formaldehyde-OSO4. This fixative stabilized nucleic acids, allowing acetone dehydration and plastic embedding without collapse of nucleic acid to the centre of the virion.", "contents": "Chromic-acid formaldehyde fixation of nucleic acids of bacteriophage phi6 and infectious bovine rhinotracheitis virus. Bacteriophage phi6 nucleic acid was present as a torus after chromic acid-formaldehyde-OSO4 fixation and acetone and propylene oxide dehydration. A herpes virus, infectious bovine rhinotracheitis virus, had its DNA mostly as a torus, collapsed in the centre, or as a network, after glutaraldehyde-OSO4 fixation, but in an uncollapsed torus or network formation after chromic acid-formaldehyde-OSO4. This fixative stabilized nucleic acids, allowing acetone dehydration and plastic embedding without collapse of nucleic acid to the centre of the virion."}
{"id": "PMID:206663", "title": "Effect of castration on the concentration of adenosine 3',5'-monophosphate in the rat pineal organ.", "content": "The concentration of adenosine 3',5'-monophosphate (cAMP) was investigated in the rat pineal organ after bilateral orchidectomy. Orchidectomy caused a decrease in pineal cAMP concentration.", "contents": "Effect of castration on the concentration of adenosine 3',5'-monophosphate in the rat pineal organ. The concentration of adenosine 3',5'-monophosphate (cAMP) was investigated in the rat pineal organ after bilateral orchidectomy. Orchidectomy caused a decrease in pineal cAMP concentration."}
{"id": "PMID:206664", "title": "Dopaminergic neurons: effect of acute and chronic morphine administration on single cell activity and transmitter metabolism.", "content": "At various time points following acute and chronic administration of morphine to rats, dopamine transmitter metabolism and neuronal activity were determined. Following acute injection of morphine (20 mg/kg intraperitoneally), dopamine cell firing rates increased slowly and steadily. This slow increase was accompanied by a similar slow increase in the accumulation of the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC). Apparent in vivo tyrosine hydroxylase activity, measured by dopa accumulation following inhibition of dopa decarboxylase, also increased. In chronically treated animals the average firing rate of dopamine cells was measured two hours after the last injection of morphine. The distribution of dopamine cell firing rates was significantly higher than in controls. DOPAC levels and in vivo tyrosine hydroxylase activity were also increased at this time. When morphine (100 mg/kg intraperitoneally) was administered to chronically treated animals 12 hours after the last injection a slow increase of firing rates was observed similar to that seen in naive animals after an acute morphine injection. In chronically morphine treated animals naloxone caused a rapid dose-dependent decrease in firing rates and DOPAC levels. In vivo tyrosine hydroxylase activity was not changed.", "contents": "Dopaminergic neurons: effect of acute and chronic morphine administration on single cell activity and transmitter metabolism. At various time points following acute and chronic administration of morphine to rats, dopamine transmitter metabolism and neuronal activity were determined. Following acute injection of morphine (20 mg/kg intraperitoneally), dopamine cell firing rates increased slowly and steadily. This slow increase was accompanied by a similar slow increase in the accumulation of the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC). Apparent in vivo tyrosine hydroxylase activity, measured by dopa accumulation following inhibition of dopa decarboxylase, also increased. In chronically treated animals the average firing rate of dopamine cells was measured two hours after the last injection of morphine. The distribution of dopamine cell firing rates was significantly higher than in controls. DOPAC levels and in vivo tyrosine hydroxylase activity were also increased at this time. When morphine (100 mg/kg intraperitoneally) was administered to chronically treated animals 12 hours after the last injection a slow increase of firing rates was observed similar to that seen in naive animals after an acute morphine injection. In chronically morphine treated animals naloxone caused a rapid dose-dependent decrease in firing rates and DOPAC levels. In vivo tyrosine hydroxylase activity was not changed."}
{"id": "PMID:206669", "title": "Clinical and electrophysiological appraisal of the significance of radicular injury in back pain.", "content": "Clinical electrophysiological studies were analysed in 60 consecutive patients with back pain with or without other evidence for a radiculopathy. These studies included needle EMG of relevant limb and paraspinal muscles as well as F responses and H reflexes recorded from the soleus muscle. Segmental denervation was found in 29 of the 60 patients. In 57 patients, abnormal slowing of the F response was present in 27, either unilaterally (25) or bilaterally (two). In 18 of 47 patients with H reflex studies, the H reflex was either unilaterally absent (12), asymmetrically prolonged (five), or bilaterally prolonged (one). Statistically significant (P less than 0.05) associations were found between (1) abnormalities of H reflexes and F responses, (2) F response slowing and radicular injury shown by EMG, (3) segmentally consistent radiographic defects and abnormalities of both H reflexes and F responses, and (4) depressed Achilles reflexes as well as sensory loss and abnormal H reflexes. No significant association, however, was present between abnormalities of EMG, F responses, or H reflexes and pain radiation by history or positive straight leg-raising tests. These data suggest that pain in radicular syndromes is related to the functioning of smaller afferent fibres.", "contents": "Clinical and electrophysiological appraisal of the significance of radicular injury in back pain. Clinical electrophysiological studies were analysed in 60 consecutive patients with back pain with or without other evidence for a radiculopathy. These studies included needle EMG of relevant limb and paraspinal muscles as well as F responses and H reflexes recorded from the soleus muscle. Segmental denervation was found in 29 of the 60 patients. In 57 patients, abnormal slowing of the F response was present in 27, either unilaterally (25) or bilaterally (two). In 18 of 47 patients with H reflex studies, the H reflex was either unilaterally absent (12), asymmetrically prolonged (five), or bilaterally prolonged (one). Statistically significant (P less than 0.05) associations were found between (1) abnormalities of H reflexes and F responses, (2) F response slowing and radicular injury shown by EMG, (3) segmentally consistent radiographic defects and abnormalities of both H reflexes and F responses, and (4) depressed Achilles reflexes as well as sensory loss and abnormal H reflexes. No significant association, however, was present between abnormalities of EMG, F responses, or H reflexes and pain radiation by history or positive straight leg-raising tests. These data suggest that pain in radicular syndromes is related to the functioning of smaller afferent fibres."}
{"id": "PMID:206670", "title": "Susceptibility of human skeletal muscle culture to influenza virus infection. Part 2. Ultrastructural cytopathology.", "content": "Cultured post-fused human skeletal muscle monolayers exposed to WSN influenza A virus were analyzed by scanning and transmission electron microscopy. At 12-14h post-inoculation (p.i.), affected mononuclear cells retracted from the cell surface, but remained anchored to the substrate by taut filar processes. Retraction was accompanied by shortening of microvilli, appearance of hemispherical cytoplasmic protrusions and corrugation of the surface proper. These changes were more pronounced at 24 and 48h p.i. The rounded, moribund mononuclear cells eventually detached from the substratum. Surface alterations were accompanied by the intracellular appearance of electron-dense nuclear inclusions (often associated with the nucleolus) and paracrystalline ribosomestudded cytoplasmic bodies, which increased in size and number with time. In myotubes, distinct surface alterations appeared later (24h p.i.). Early myotube retraction was accompanied by accentuation of the longitudinally oriented surface pleats and appearance of \"blebs\" followed by cell-rounding. At 48-72 h, many myotubes detached from the substratum. The surfaces of those still adhering appeared corrugated. Intranuclear and cytoplasmic inclusions accumulated, and budding virions, often filamentous, could be demonstrated at the plasmalemma of mononuclear cells and myotubes. Late (end-stage) cytopathic effects included clumping of chromatin, breakdown of the nuclear envelope, disappearance of cortical and endoplasmic cytofilaments, mitochondrial swelling, and vesiculation of surface membranes. The lesions leading to cell injury and cell death appeared to be due to massive accumulation of virus-induced products that altered cellular metabolism, with physical and functional abnormalities of surface membranes.", "contents": "Susceptibility of human skeletal muscle culture to influenza virus infection. Part 2. Ultrastructural cytopathology. Cultured post-fused human skeletal muscle monolayers exposed to WSN influenza A virus were analyzed by scanning and transmission electron microscopy. At 12-14h post-inoculation (p.i.), affected mononuclear cells retracted from the cell surface, but remained anchored to the substrate by taut filar processes. Retraction was accompanied by shortening of microvilli, appearance of hemispherical cytoplasmic protrusions and corrugation of the surface proper. These changes were more pronounced at 24 and 48h p.i. The rounded, moribund mononuclear cells eventually detached from the substratum. Surface alterations were accompanied by the intracellular appearance of electron-dense nuclear inclusions (often associated with the nucleolus) and paracrystalline ribosomestudded cytoplasmic bodies, which increased in size and number with time. In myotubes, distinct surface alterations appeared later (24h p.i.). Early myotube retraction was accompanied by accentuation of the longitudinally oriented surface pleats and appearance of \"blebs\" followed by cell-rounding. At 48-72 h, many myotubes detached from the substratum. The surfaces of those still adhering appeared corrugated. Intranuclear and cytoplasmic inclusions accumulated, and budding virions, often filamentous, could be demonstrated at the plasmalemma of mononuclear cells and myotubes. Late (end-stage) cytopathic effects included clumping of chromatin, breakdown of the nuclear envelope, disappearance of cortical and endoplasmic cytofilaments, mitochondrial swelling, and vesiculation of surface membranes. The lesions leading to cell injury and cell death appeared to be due to massive accumulation of virus-induced products that altered cellular metabolism, with physical and functional abnormalities of surface membranes."}
{"id": "PMID:206671", "title": "Membranous neuronal and neuroglial inclusions produced by intracerebral injection of Suramin.", "content": "A single intracerebral injection of 5 micrometer of the trypanocidal drug Suramin, into the left hemisphere of young rats, resulted in the formation of membranous inclusion bodies within the perikarya and processes of neurones and neuroglia. These inclusion bodies were round or oval in shape and 0.5-3.0 micrometer in their longest diameter. They were bounded by a single trilaminar membrane and contained closely packed membranes in concentric, curved or parallel arrays. The inclusions were distributed throughout the cerebral cortex and underlying hippocampus at the injection site, and in reduced numbers up to 1 mm anteriorly and posteriorly from it. They formed within 22 hr of the injection and had increased in numbers and in the complexity of their arrays 3 days after injection. Within 14 days, the inclusions were markedly reduced in number. As Suramin is known to inhibit lysosomal hydrolases required for the degradation of proteins, glycolipids and mucopolysaccharides, the membranous inclusions could form as a result of the accumulation of these substances within lysosomes. These experiments indicate a possible experimental model for storage diseases. It is hoped that the extension of this paradigm to other enzyme inhibitors will provide a new means of identifying some of the unusual inclusions that can be found in neurones and neuroglia (Rees 1975).", "contents": "Membranous neuronal and neuroglial inclusions produced by intracerebral injection of Suramin. A single intracerebral injection of 5 micrometer of the trypanocidal drug Suramin, into the left hemisphere of young rats, resulted in the formation of membranous inclusion bodies within the perikarya and processes of neurones and neuroglia. These inclusion bodies were round or oval in shape and 0.5-3.0 micrometer in their longest diameter. They were bounded by a single trilaminar membrane and contained closely packed membranes in concentric, curved or parallel arrays. The inclusions were distributed throughout the cerebral cortex and underlying hippocampus at the injection site, and in reduced numbers up to 1 mm anteriorly and posteriorly from it. They formed within 22 hr of the injection and had increased in numbers and in the complexity of their arrays 3 days after injection. Within 14 days, the inclusions were markedly reduced in number. As Suramin is known to inhibit lysosomal hydrolases required for the degradation of proteins, glycolipids and mucopolysaccharides, the membranous inclusions could form as a result of the accumulation of these substances within lysosomes. These experiments indicate a possible experimental model for storage diseases. It is hoped that the extension of this paradigm to other enzyme inhibitors will provide a new means of identifying some of the unusual inclusions that can be found in neurones and neuroglia (Rees 1975)."}
{"id": "PMID:206672", "title": "Sensitization to myelin basic protein in attacks of multiple sclerosis. A preliminary report.", "content": "Recent attempts to detect the presence of antibody to encephalitogenic basic protein in multiple sclerosis have generally been unsuccessful. The utilization of a new system of double immunodiffusion in detecting such antibody in EAE serum prompted us to apply this method in the search of such antibody MS sera. In our preliminary investigation of 67 sera, antibody was detectable in MS sera, but it was most often found during convalescence rather than an acute exacerbation of illness. Antibody was also found in several myasthenic patients, and occasionally in subjects with other neurological disease.", "contents": "Sensitization to myelin basic protein in attacks of multiple sclerosis. A preliminary report. Recent attempts to detect the presence of antibody to encephalitogenic basic protein in multiple sclerosis have generally been unsuccessful. The utilization of a new system of double immunodiffusion in detecting such antibody in EAE serum prompted us to apply this method in the search of such antibody MS sera. In our preliminary investigation of 67 sera, antibody was detectable in MS sera, but it was most often found during convalescence rather than an acute exacerbation of illness. Antibody was also found in several myasthenic patients, and occasionally in subjects with other neurological disease."}
{"id": "PMID:206674", "title": "Frequency-response analysis of vestibular-induced neck reflex in cat. I. Characteristics of neural transmission from horizontal semicircular canal to neck motoneurons.", "content": "1. Vestibular-induced neck muscle reflexes (vestibulocollic reflexes) were studied with frequency-response methods in unanesthetized, decerebrate cats. The horizontal semicircular canals were stimulated by oscillation of the turntable and EMG activity was recorded from neck extensor muscles. 2. The maximum firing rate of each motor unit was less than 40 spikes/s. The motor units were classified by their maximum firing rates into two groups: HF (high frequency) units which could fire above 20 spikes/s and LF (low frequency) units which could not exceed 20 spikes/s of firing. The HF units had larger gains than the LF units on the average. 3. Compound EMGs, which presumably represent activity of the whole muscle, were examined at different frequencies of stimulation. The gain of compound EMG responses depended on the spontaneous activity. When the spontaneous activity was low or too high, the gain was small. There was an intermediate spontaneous activity level at which the gain became maximal. 4. The phase lag and the gain of the frequency response were represented in a Bode diagram with respect to angular acceleration. The transfer function of the system from the vestibular nuclei to neck EMG activity was estimated by assuming a first-order lag-lead system. A phase lag of 70-80 degrees (0.05 Hz) was found between the averaged activity of vestibular nucleus neurons and cervical motor activity. A positive correlation was observed between the phase lag and the gain of each motor unit. These results cannot be attributed solely to the action of the vestibulospinal tract, but suggest the existence of a neural intergrator in the vestibulocollic reflex arc.", "contents": "Frequency-response analysis of vestibular-induced neck reflex in cat. I. Characteristics of neural transmission from horizontal semicircular canal to neck motoneurons. 1. Vestibular-induced neck muscle reflexes (vestibulocollic reflexes) were studied with frequency-response methods in unanesthetized, decerebrate cats. The horizontal semicircular canals were stimulated by oscillation of the turntable and EMG activity was recorded from neck extensor muscles. 2. The maximum firing rate of each motor unit was less than 40 spikes/s. The motor units were classified by their maximum firing rates into two groups: HF (high frequency) units which could fire above 20 spikes/s and LF (low frequency) units which could not exceed 20 spikes/s of firing. The HF units had larger gains than the LF units on the average. 3. Compound EMGs, which presumably represent activity of the whole muscle, were examined at different frequencies of stimulation. The gain of compound EMG responses depended on the spontaneous activity. When the spontaneous activity was low or too high, the gain was small. There was an intermediate spontaneous activity level at which the gain became maximal. 4. The phase lag and the gain of the frequency response were represented in a Bode diagram with respect to angular acceleration. The transfer function of the system from the vestibular nuclei to neck EMG activity was estimated by assuming a first-order lag-lead system. A phase lag of 70-80 degrees (0.05 Hz) was found between the averaged activity of vestibular nucleus neurons and cervical motor activity. A positive correlation was observed between the phase lag and the gain of each motor unit. These results cannot be attributed solely to the action of the vestibulospinal tract, but suggest the existence of a neural intergrator in the vestibulocollic reflex arc."}
{"id": "PMID:206675", "title": "Effects of diet on swine glyceride lipid metabolism.", "content": "Swine were fed equal amounts of isoenergetic-isonitrogenous diets with low-fat or high-fat content. The high-fat diet, as well as starvation, suppressed the synthesis of fatty acid from glucose in adipose tissue. Diet had no effect on adipose tissue enzymes associated with glyceride synthesis; whereas starvation caused all activities expressed per g tissue to decrease. The hepatic enzyme activities associated with glyceride synthesis tended to be greater in swine fed the the high-fat diet compared to the low-fat diet. Starvation lowered the hepatic esterification of glycerol-3-phosphate but did not influence other enzymes.", "contents": "Effects of diet on swine glyceride lipid metabolism. Swine were fed equal amounts of isoenergetic-isonitrogenous diets with low-fat or high-fat content. The high-fat diet, as well as starvation, suppressed the synthesis of fatty acid from glucose in adipose tissue. Diet had no effect on adipose tissue enzymes associated with glyceride synthesis; whereas starvation caused all activities expressed per g tissue to decrease. The hepatic enzyme activities associated with glyceride synthesis tended to be greater in swine fed the the high-fat diet compared to the low-fat diet. Starvation lowered the hepatic esterification of glycerol-3-phosphate but did not influence other enzymes."}
{"id": "PMID:206677", "title": "Interferon production in children with respiratory syncytial, influenza, and parainfluenza virus infections.", "content": "To better understand the recovery process of infants with lower respiratory tract disease due to respiratory syncytial virus, the production of interferon by 129 children (ages 10 days to 24 months) with RSV infection was compared to that of 20 children with influenza (ages 1 to 36 months), and 37 children with parainfluenza virus infection (ages 4 to 66 months). Interferon assays of 285 nasal washes from children with RSV revealed that interferon production occurred in only 5 (4%) of the children. Significantly more children infected with infleunza virus, 55% (P less than 0.001), and parainfluenza virus, 30% (P less than 0.001), produced interferon. In addition, the quantity of interferon produced by children with RSV (geometric mean titer = 2) was significantly less than that of children with influenza (GMT = 26.8, P less than 0.001) and parainfluenza virus (GMT = 23.5, P less than 0.001). In the children infected with RSV, in constrast to those with influenza, interferon detection was not associated with diminished shedding of virus.", "contents": "Interferon production in children with respiratory syncytial, influenza, and parainfluenza virus infections. To better understand the recovery process of infants with lower respiratory tract disease due to respiratory syncytial virus, the production of interferon by 129 children (ages 10 days to 24 months) with RSV infection was compared to that of 20 children with influenza (ages 1 to 36 months), and 37 children with parainfluenza virus infection (ages 4 to 66 months). Interferon assays of 285 nasal washes from children with RSV revealed that interferon production occurred in only 5 (4%) of the children. Significantly more children infected with infleunza virus, 55% (P less than 0.001), and parainfluenza virus, 30% (P less than 0.001), produced interferon. In addition, the quantity of interferon produced by children with RSV (geometric mean titer = 2) was significantly less than that of children with influenza (GMT = 26.8, P less than 0.001) and parainfluenza virus (GMT = 23.5, P less than 0.001). In the children infected with RSV, in constrast to those with influenza, interferon detection was not associated with diminished shedding of virus."}
{"id": "PMID:206678", "title": "Bilateral massive nephroblastomatosis in infancy.", "content": "This report describes an infant with bilateral diffuse nephroblastomatosis, illustrating the typical clinical and pathologic characteristics that allow it to be differentiated from true bilateral Wilms' tumor.", "contents": "Bilateral massive nephroblastomatosis in infancy. This report describes an infant with bilateral diffuse nephroblastomatosis, illustrating the typical clinical and pathologic characteristics that allow it to be differentiated from true bilateral Wilms' tumor."}
{"id": "PMID:206683", "title": "Quantal analysis of the size of excitatory post-synaptic potentials at synapses between hair cells and afferent nerve fibres in goldfish.", "content": "1. A statistical analysis has been made of the transmitter release at the hair cell afferent fibre synapse in the sacculus of the goldfish, using the amplitude of the excitatory post-synaptic potentials (e.p.s.p.s) in response to stimulus tone as a measure of the transmitter release under application of tetrodotoxin. 2. Application of binomial statistics allowed a direct calculation of the mean probability of release (p) and the readily available store (n), and the X2-test showed that the binomial predictions fitted fairly well with the observed distribution of the responses. 3. Adaptive rundown of e.p.s.p.s during sound stimulation, i.e. the successive rundown in the size of the mean quantal content (m), was found to be associated with a reduction in the size of parameter n, but not of p. 4. A marked negative correlation was demonstrated between the amplitude of two consecutive e.p.s.p.s, supporting the depletion hypothesis of the adaptive rundown of e.p.s.p.s. 5. The increase in the e.p.s.p. amplitude and the increase in the mean quantal content, m, brought about by an increase in the tone intensity were found mostly explicable in terms of an increase in the statistical parameter n. The probability parameter p was found largely in invariable, although in certain instances the increase in m was also accompanied by a slight increase in the parameter p.", "contents": "Quantal analysis of the size of excitatory post-synaptic potentials at synapses between hair cells and afferent nerve fibres in goldfish. 1. A statistical analysis has been made of the transmitter release at the hair cell afferent fibre synapse in the sacculus of the goldfish, using the amplitude of the excitatory post-synaptic potentials (e.p.s.p.s) in response to stimulus tone as a measure of the transmitter release under application of tetrodotoxin. 2. Application of binomial statistics allowed a direct calculation of the mean probability of release (p) and the readily available store (n), and the X2-test showed that the binomial predictions fitted fairly well with the observed distribution of the responses. 3. Adaptive rundown of e.p.s.p.s during sound stimulation, i.e. the successive rundown in the size of the mean quantal content (m), was found to be associated with a reduction in the size of parameter n, but not of p. 4. A marked negative correlation was demonstrated between the amplitude of two consecutive e.p.s.p.s, supporting the depletion hypothesis of the adaptive rundown of e.p.s.p.s. 5. The increase in the e.p.s.p. amplitude and the increase in the mean quantal content, m, brought about by an increase in the tone intensity were found mostly explicable in terms of an increase in the statistical parameter n. The probability parameter p was found largely in invariable, although in certain instances the increase in m was also accompanied by a slight increase in the parameter p."}
{"id": "PMID:206690", "title": "Effect of cholinergic antagonists on sympathetic ganglionic transmission of vasomotor reflexes from the carotid baroreceptors and chemoreceptors of the dog.", "content": "1. In anaesthetized dogs the reflex vascular resistance changes in a perfused hind limb were studied following carotid baroreceptor or chemoreceptor stimulation. 2. The observed rises in resistance were sympathetically mediated and thus provided a means of studying the action of the cholinergic antagonists on the sympathetic ganglion transmission. 3. The reflex response to carotid baroreceptor stimulation produced by lowering the pressure in the carotid sinuses was abolished by hexamethonium bromide but not reduced by hyoscine methyl bromide. 4. The reflex response to carotid body chemoreceptor stimulation, by hypoxia, was not altered by hexamethonium bromide but was greatly reduced by the hyoscine methyl bromide. No reflex response was seen when both antagonists were present. 5. These results indicate that sympathetic ganglion synaptic transmission during the baroreceptor reflex is mediated by nicotinic receptor activation. The transmission evoked by chemoreceptor stimulation involves muscarinic receptors with a subsidiary nicotinic pathway. High doses of an antagonist were necessary to block the muscarinic component of transmission and this is discussed in relation to previous work. 6. No non-cholinergic transmission of the reflex responses was observed.", "contents": "Effect of cholinergic antagonists on sympathetic ganglionic transmission of vasomotor reflexes from the carotid baroreceptors and chemoreceptors of the dog. 1. In anaesthetized dogs the reflex vascular resistance changes in a perfused hind limb were studied following carotid baroreceptor or chemoreceptor stimulation. 2. The observed rises in resistance were sympathetically mediated and thus provided a means of studying the action of the cholinergic antagonists on the sympathetic ganglion transmission. 3. The reflex response to carotid baroreceptor stimulation produced by lowering the pressure in the carotid sinuses was abolished by hexamethonium bromide but not reduced by hyoscine methyl bromide. 4. The reflex response to carotid body chemoreceptor stimulation, by hypoxia, was not altered by hexamethonium bromide but was greatly reduced by the hyoscine methyl bromide. No reflex response was seen when both antagonists were present. 5. These results indicate that sympathetic ganglion synaptic transmission during the baroreceptor reflex is mediated by nicotinic receptor activation. The transmission evoked by chemoreceptor stimulation involves muscarinic receptors with a subsidiary nicotinic pathway. High doses of an antagonist were necessary to block the muscarinic component of transmission and this is discussed in relation to previous work. 6. No non-cholinergic transmission of the reflex responses was observed."}
{"id": "PMID:206691", "title": "The effects of nerve growth factor and its antiserum on synapses in the superior cervical ganglion of the guinea-pig.", "content": "1. The effects of nerve growth factor (NGF) and its antiserum on synapses in the superior cervical ganglion of the guinea-pig have been examined by intracellular recording and electron microscopy. 2. Exogenous NGF, supplied locally from a silicone rubber pellet implanted near ganglia for 4-7 days, had little effect on either the function or the number of ganglionic synapses. 3. However, the depression of synaptic transmission and loss of synaptic contacts on ganglion cells which follow post-ganglionic axotomy were diminished by about 50% in the presence of exogenous NGF. 4. Other post-axotomy changes such as the development of subthreshold regenerative responses in neuronal processes, the appearance of ultrastructurally abnormal neuronal profiles suggesting rapid membrane turnover, and the cytoplasmic and nuclear changes characteristic of \"chromatolysis\", were also largely prevented by exogenous NGF. 5. Systemic treatment of neonatal and young adult guinea-pigs with antiserum to NGF for 4-5 days caused depression of intracellularly recorded synaptic responses within 5-8 days of the end of antiserum administration. Synapse counts in electron microscopical sections from these ganglia showed only about half as many contacts as in control ganglia from animals receiving normal rabbit serum. 6. These findings suggest that the loss of synapses from sympathetic neurones which follows axotomy results from a reduction in the amount of NGF supplied to ganglion cells. A corollary is that, among other biological roles, NGF is required by peripheral sympathetic neurones to maintain the synapses they receive.", "contents": "The effects of nerve growth factor and its antiserum on synapses in the superior cervical ganglion of the guinea-pig. 1. The effects of nerve growth factor (NGF) and its antiserum on synapses in the superior cervical ganglion of the guinea-pig have been examined by intracellular recording and electron microscopy. 2. Exogenous NGF, supplied locally from a silicone rubber pellet implanted near ganglia for 4-7 days, had little effect on either the function or the number of ganglionic synapses. 3. However, the depression of synaptic transmission and loss of synaptic contacts on ganglion cells which follow post-ganglionic axotomy were diminished by about 50% in the presence of exogenous NGF. 4. Other post-axotomy changes such as the development of subthreshold regenerative responses in neuronal processes, the appearance of ultrastructurally abnormal neuronal profiles suggesting rapid membrane turnover, and the cytoplasmic and nuclear changes characteristic of \"chromatolysis\", were also largely prevented by exogenous NGF. 5. Systemic treatment of neonatal and young adult guinea-pigs with antiserum to NGF for 4-5 days caused depression of intracellularly recorded synaptic responses within 5-8 days of the end of antiserum administration. Synapse counts in electron microscopical sections from these ganglia showed only about half as many contacts as in control ganglia from animals receiving normal rabbit serum. 6. These findings suggest that the loss of synapses from sympathetic neurones which follows axotomy results from a reduction in the amount of NGF supplied to ganglion cells. A corollary is that, among other biological roles, NGF is required by peripheral sympathetic neurones to maintain the synapses they receive."}
{"id": "PMID:206696", "title": "[The role of early nephrotomography in renal insufficiency (author's transl)].", "content": "The use of early nephrotomography has added a supplementary functional dimension to intravenous urography films, made after the rapid injection of 60 ml of contrast media in the form of an embolus. This method enables the corticomedullary junction to be visualized in the nephrography, which is an important point in differential diagnosis. An analysis is made of the results obtained from early nephrotomographies in 50 patients with acute or chronic renal insufficiency. Satisfactory nephrographies were obtained in all cases and the position and size of the kidneys could be established. Certain nephrotomographic abnormalities appear more frequently during the course of some types of chronic nephropathies, and this can assist aetiological classification. The existence of dilated secretory cavities in the superior part of the kidney can be established very quickly. In this way it is possible to differentiate clearly between parenchymatous nephropathies and those due to obstruction, such as when oliguria or anuria is present. The presence of a persistent homogenous nephrography would evoke, under these same conditions, an acute medical nephropathy.", "contents": "[The role of early nephrotomography in renal insufficiency (author's transl)]. The use of early nephrotomography has added a supplementary functional dimension to intravenous urography films, made after the rapid injection of 60 ml of contrast media in the form of an embolus. This method enables the corticomedullary junction to be visualized in the nephrography, which is an important point in differential diagnosis. An analysis is made of the results obtained from early nephrotomographies in 50 patients with acute or chronic renal insufficiency. Satisfactory nephrographies were obtained in all cases and the position and size of the kidneys could be established. Certain nephrotomographic abnormalities appear more frequently during the course of some types of chronic nephropathies, and this can assist aetiological classification. The existence of dilated secretory cavities in the superior part of the kidney can be established very quickly. In this way it is possible to differentiate clearly between parenchymatous nephropathies and those due to obstruction, such as when oliguria or anuria is present. The presence of a persistent homogenous nephrography would evoke, under these same conditions, an acute medical nephropathy."}
{"id": "PMID:206698", "title": "Studies in the (+)-morphinan series. 5. Synthesis and biological properties of (+)-naloxone.", "content": "(+)-Naloxone was prepared in 26% overall yield in eight steps from (+)-7-bromodihydrocodeinone dimethyl ketal by a synthesis which excluded enantiomeric contamination. (+)-Naloxone was examined in three assay systems and found to have no more than 1/1000(-1)/10 000th the activity of (-)-naloxone; it can, thus, serve to test the stereospecificity of the biochemical and pharmacological actions of (-)-naloxone.", "contents": "Studies in the (+)-morphinan series. 5. Synthesis and biological properties of (+)-naloxone. (+)-Naloxone was prepared in 26% overall yield in eight steps from (+)-7-bromodihydrocodeinone dimethyl ketal by a synthesis which excluded enantiomeric contamination. (+)-Naloxone was examined in three assay systems and found to have no more than 1/1000(-1)/10 000th the activity of (-)-naloxone; it can, thus, serve to test the stereospecificity of the biochemical and pharmacological actions of (-)-naloxone."}
{"id": "PMID:206702", "title": "Inhibition of DNA synthesis and alteration of cyclic adenosine 3',5'-monophosphate levels in RSa cells by human leukocyte interferon.", "content": "Human leukocyte interferon inhibits the proliferation of the virus-transformed human embryonic cells RSa. Incorporation of [3H]thymidine (TdR) into an intracellular pool and the activity of TdR kinase were reduced in the interferon-treated RSa cell culture. High-degree (90%) inhibition of [3H]TdR incorporation was associated with concentrations of added interferon that produced more than a twofold increase in the intracellular cyclic AMP (cAMP) level, and low-degree inhibition was associated with smaller increases in cAMP. In the IFr cell culture, which is relatively resistant to the anticellular action of interferon, considerably less inhibition of TdR incorporation and a slight increase in cAMP were observed. Extracellularly added dibutyryl-cAMP inhibited the proliferation of both RSa and IFr cells to almost the same degree. A decrease in cAMP level and the initiation of DNA synthesis of G1-phase-arrested RSa cells by serum addition were prevented when cells were pretreated with interferon. These results indicated that intracellular cAMP may mediate the inhibitory effect of interferon on DNA synthesis and cell growth.", "contents": "Inhibition of DNA synthesis and alteration of cyclic adenosine 3',5'-monophosphate levels in RSa cells by human leukocyte interferon. Human leukocyte interferon inhibits the proliferation of the virus-transformed human embryonic cells RSa. Incorporation of [3H]thymidine (TdR) into an intracellular pool and the activity of TdR kinase were reduced in the interferon-treated RSa cell culture. High-degree (90%) inhibition of [3H]TdR incorporation was associated with concentrations of added interferon that produced more than a twofold increase in the intracellular cyclic AMP (cAMP) level, and low-degree inhibition was associated with smaller increases in cAMP. In the IFr cell culture, which is relatively resistant to the anticellular action of interferon, considerably less inhibition of TdR incorporation and a slight increase in cAMP were observed. Extracellularly added dibutyryl-cAMP inhibited the proliferation of both RSa and IFr cells to almost the same degree. A decrease in cAMP level and the initiation of DNA synthesis of G1-phase-arrested RSa cells by serum addition were prevented when cells were pretreated with interferon. These results indicated that intracellular cAMP may mediate the inhibitory effect of interferon on DNA synthesis and cell growth."}
{"id": "PMID:206703", "title": "Response of plasma histaminase activity to heparin in normal subjects and in patients with small cell carcinoma of the lung.", "content": "Plasma histaminase (PH) activity only partially reflected the consistently high activity of histaminase in tumor tissue of patients with small cell carcinoma of the lung (SCC). To determine whether heparin might release histaminase from tumor tissue into the circulation as it does from some normal tissues, we studied the response of PH activity to small doses of heparin in 41 patients with SCC and in 57 normal subjects. In patients with SCC, the initial mean PH activity (2.0 U/m) was not different from that in normal subjects (1.7 U/ml). After heparin administration, the mean PH activity was no different between the 2 groups (patients with SCC, 3.1 U/ml; normal subjects, 3.5 U/ml). In both groups, the higher the initial PH activity, the greater the magnitude of the PH activity response to heparin. This relationship was linear (normal subjects, r = 0.88; patients with SCC, r = 0.91). However, in patients with SCC, the increase in post-heparin PH activity, as related to the basal levels, was significantly less than that in normal subjects (P less than 0.001 by analysis of covariance). The data suggested that heparin did not affect the release of histaminase from tumor tissue into plasma to the same degree as it promoted the enzyme's entry from normal tissue sources. The differences between the groups may enable us to differentiate between selected patients with SCC and normal subjects with borderline high PH activity values.", "contents": "Response of plasma histaminase activity to heparin in normal subjects and in patients with small cell carcinoma of the lung. Plasma histaminase (PH) activity only partially reflected the consistently high activity of histaminase in tumor tissue of patients with small cell carcinoma of the lung (SCC). To determine whether heparin might release histaminase from tumor tissue into the circulation as it does from some normal tissues, we studied the response of PH activity to small doses of heparin in 41 patients with SCC and in 57 normal subjects. In patients with SCC, the initial mean PH activity (2.0 U/m) was not different from that in normal subjects (1.7 U/ml). After heparin administration, the mean PH activity was no different between the 2 groups (patients with SCC, 3.1 U/ml; normal subjects, 3.5 U/ml). In both groups, the higher the initial PH activity, the greater the magnitude of the PH activity response to heparin. This relationship was linear (normal subjects, r = 0.88; patients with SCC, r = 0.91). However, in patients with SCC, the increase in post-heparin PH activity, as related to the basal levels, was significantly less than that in normal subjects (P less than 0.001 by analysis of covariance). The data suggested that heparin did not affect the release of histaminase from tumor tissue into plasma to the same degree as it promoted the enzyme's entry from normal tissue sources. The differences between the groups may enable us to differentiate between selected patients with SCC and normal subjects with borderline high PH activity values."}
{"id": "PMID:206706", "title": "Gangliosides of liver tumors induced by N-2-fluorenylacetamide. I. Ganglioside alterations in liver tumorigenesis and normal development.", "content": "Hyperplastic nodules and hepatocellular carcinomas were induced in livers of rats by a low-protein diet containing 0.05% of the carcinogen N-2-fluorenylacetamide. Ganglioside amounts and composition were determined for histologically different hepatocellular carcinomas and compared with those for control livers, hyperplastic nodules, and liver tissue surrounding hepatomas and nodules as well as those for livers of fetal, newborn, 1-week-old, weanling, and adult Sprague-Dawley rats. Ganglioside sialic acid levels were elevated above those of normal adult liver in all liver tissues following the carcinogen treatment regimen. Livers of fetal and newborn rats contained nearly twice the amount of ganglioside sialic acid on a protein or DNA basis as did livers of adult rats. Analyses of individual nodules and hepatomas revealed two populations of tumors in which the levels of ganglioside sialic acid were 2.3 and 3.8 times normal. Ganglioside sialic acid content was at hepatoma levels in small nodules. Individual gangliosides were evenly distributed between products of the monosialoganglioside and disialoganglioside pathways in normal liver with a ratio of [N-acetylneuraminic acid (sialic acid)] (NAN)-galactose (Gal)-N-acetylgalactosamine (GalNAc)-(NAN)-Gal-glucose (Glc)-ceramide (Cer) (GD1a) to Gal-GalNAc-(NAN)2-Gal-Glc-Cer (GD1b) of about one. In contrast, the monosialogangliosides predominated in liver tissues following administration of the carcinogen. Increased levels of specific monosialogangliosides were present in nodules, in liver of carcinogen-treated animals prior to the appearance of tumors, and in the liver tissues surrounding nodules and hepatomas. In single hepatomas, ganglioside patterns correlated with tumorigenicity. A well-differentiated hepatoma had a normal complement of most gangliosides but was deficient in trisialogangliosides. In a poorly diferentiated but well-circumscribed hepatoma, the relative levels of all higher gangliosides were reduced. The monosialoganglioside Gal-GalNAc-(NAN)-Gal-Glc-Cer (GM1) accounted for 80% of the total ganglioside in a poorly circumscribed and poorly differentiated hepatoma. The ganglioside pattern of fetal livers most closely resembled that of a poorly differentiated hepatoma. During the first week post natum, levels of all higher monosialogangliosides and disialogangliosides declined, but the decline was most pronounced for gangliosides GM1 and GD1a. The ratio of GM1 + GD1a to GD1b + NAN-Gal-GalNAc-(NAN)2-Gal-Glc-Cer or (NAN)3-Gal-Glc-Cer (GT), used as an index of the relative predominance of the monoslaloganglioside and disialoganglioside pathways, fell from 2.7 for fetal liver to 0.4 for adult liver. Pools of precursor gangliosides increased during development, transiently for GalNAc-(NAN)-Gal-Glc-Cer and for more than 3 weeks for NAN-Gal-Glc-Cer. When hyperplastic nodules and hepatocellular carcinomas were compared, a reverse pattern was observed. The ratio of GM1 + GD1a to GD1b + GT rose steadily to values of 2.7 and 11...", "contents": "Gangliosides of liver tumors induced by N-2-fluorenylacetamide. I. Ganglioside alterations in liver tumorigenesis and normal development. Hyperplastic nodules and hepatocellular carcinomas were induced in livers of rats by a low-protein diet containing 0.05% of the carcinogen N-2-fluorenylacetamide. Ganglioside amounts and composition were determined for histologically different hepatocellular carcinomas and compared with those for control livers, hyperplastic nodules, and liver tissue surrounding hepatomas and nodules as well as those for livers of fetal, newborn, 1-week-old, weanling, and adult Sprague-Dawley rats. Ganglioside sialic acid levels were elevated above those of normal adult liver in all liver tissues following the carcinogen treatment regimen. Livers of fetal and newborn rats contained nearly twice the amount of ganglioside sialic acid on a protein or DNA basis as did livers of adult rats. Analyses of individual nodules and hepatomas revealed two populations of tumors in which the levels of ganglioside sialic acid were 2.3 and 3.8 times normal. Ganglioside sialic acid content was at hepatoma levels in small nodules. Individual gangliosides were evenly distributed between products of the monosialoganglioside and disialoganglioside pathways in normal liver with a ratio of [N-acetylneuraminic acid (sialic acid)] (NAN)-galactose (Gal)-N-acetylgalactosamine (GalNAc)-(NAN)-Gal-glucose (Glc)-ceramide (Cer) (GD1a) to Gal-GalNAc-(NAN)2-Gal-Glc-Cer (GD1b) of about one. In contrast, the monosialogangliosides predominated in liver tissues following administration of the carcinogen. Increased levels of specific monosialogangliosides were present in nodules, in liver of carcinogen-treated animals prior to the appearance of tumors, and in the liver tissues surrounding nodules and hepatomas. In single hepatomas, ganglioside patterns correlated with tumorigenicity. A well-differentiated hepatoma had a normal complement of most gangliosides but was deficient in trisialogangliosides. In a poorly diferentiated but well-circumscribed hepatoma, the relative levels of all higher gangliosides were reduced. The monosialoganglioside Gal-GalNAc-(NAN)-Gal-Glc-Cer (GM1) accounted for 80% of the total ganglioside in a poorly circumscribed and poorly differentiated hepatoma. The ganglioside pattern of fetal livers most closely resembled that of a poorly differentiated hepatoma. During the first week post natum, levels of all higher monosialogangliosides and disialogangliosides declined, but the decline was most pronounced for gangliosides GM1 and GD1a. The ratio of GM1 + GD1a to GD1b + NAN-Gal-GalNAc-(NAN)2-Gal-Glc-Cer or (NAN)3-Gal-Glc-Cer (GT), used as an index of the relative predominance of the monoslaloganglioside and disialoganglioside pathways, fell from 2.7 for fetal liver to 0.4 for adult liver. Pools of precursor gangliosides increased during development, transiently for GalNAc-(NAN)-Gal-Glc-Cer and for more than 3 weeks for NAN-Gal-Glc-Cer. When hyperplastic nodules and hepatocellular carcinomas were compared, a reverse pattern was observed. The ratio of GM1 + GD1a to GD1b + GT rose steadily to values of 2.7 and 11..."}
{"id": "PMID:206708", "title": "Tumor antigen induction by the envelope-defective Bryan strain of Rous sarcoma viruses.", "content": "Chicken, quail, and turkey cells were infected and/or transformed by various avian leukosis or sarcoma oncovirus (ALSV) strains as well as by the envelope-defective Bryan high-titer strain of Rous sarcoma virus [BH-RSV(-)]. All fibroblast-transforming avian sarcoma viruses (ASV), including BH-RSV(-), were able to induce the expression of the previously described avian tumor-specific cell-surface antigen(s) (TSSA). Thus TSSA was group-specific for all tested transforming ASV. Since BH-RSV(-) is a stable deletion mutant lacking the capacity to code for the 85 000d major virus envelope glycoprotein (gp85), it seemed unlikely that the group-specific antigen determinants of gp85 that were recently detected on ALSV-infected cells could account for TSSA expression.", "contents": "Tumor antigen induction by the envelope-defective Bryan strain of Rous sarcoma viruses. Chicken, quail, and turkey cells were infected and/or transformed by various avian leukosis or sarcoma oncovirus (ALSV) strains as well as by the envelope-defective Bryan high-titer strain of Rous sarcoma virus [BH-RSV(-)]. All fibroblast-transforming avian sarcoma viruses (ASV), including BH-RSV(-), were able to induce the expression of the previously described avian tumor-specific cell-surface antigen(s) (TSSA). Thus TSSA was group-specific for all tested transforming ASV. Since BH-RSV(-) is a stable deletion mutant lacking the capacity to code for the 85 000d major virus envelope glycoprotein (gp85), it seemed unlikely that the group-specific antigen determinants of gp85 that were recently detected on ALSV-infected cells could account for TSSA expression."}
{"id": "PMID:206709", "title": "Restriction to the cell nucleus of virus-induced host RNA's in a rat kidney tumor induced by polyoma virus.", "content": "RNA transcripts of repetitive DNA of WF rat kidney, which were derepressed during transformation by polyoma virus, were not transported to the cytoplasm in the tumor cells. Transcripts of repetitive DNA found in the normal cell nucleus were all transported to the cytoplasm in the tumor cells, including those restricted to the nuclei in the normal cells.", "contents": "Restriction to the cell nucleus of virus-induced host RNA's in a rat kidney tumor induced by polyoma virus. RNA transcripts of repetitive DNA of WF rat kidney, which were derepressed during transformation by polyoma virus, were not transported to the cytoplasm in the tumor cells. Transcripts of repetitive DNA found in the normal cell nucleus were all transported to the cytoplasm in the tumor cells, including those restricted to the nuclei in the normal cells."}
{"id": "PMID:206710", "title": "Pathology of hepatomas and other liver abnormalities in English sole (Parophrys vetulus) from the Duwamish River estuary, Seattle, Washington.", "content": "Liver abnormalities were found, by gross and histopathologic examination, in 92% of the English sole (Parophrys vetulus) from the Duwamish River Estuary, Seattle, Washington. Hepatomas were found in 32% (20 of 62) of the English sole. Other observed liver aberrations included increased fatty vacuolation, congestion, structure disarray, increased size and number of melanin-macrophage centers, centrolobular fatty degeneration and necrosis, increased amounts of perivascular connective tissue, intercellular melanin deposits, and hepatocellular hypertrophy often associated with the presence of bizarre nuclei and/or multiple nucleoli. Livers evidencing microscopic lesions were usually discolored. Livers containing hepatomas were often mottled yellow or tan and brown; occasionally, hepatomas were visible as tan or white nodules. Although the cause(s) of the liver abnormalities has not been conclusively identified, chemical analyses of Duwamish River English sole have detected polychlorinated biphenyl (PCB) levels of about 1.5 ppm (dry wt) in total body tissue. Many of the above-mentioned abnormalities, with the exception of hepatomas, have been observed in fish exposed to PCB's.", "contents": "Pathology of hepatomas and other liver abnormalities in English sole (Parophrys vetulus) from the Duwamish River estuary, Seattle, Washington. Liver abnormalities were found, by gross and histopathologic examination, in 92% of the English sole (Parophrys vetulus) from the Duwamish River Estuary, Seattle, Washington. Hepatomas were found in 32% (20 of 62) of the English sole. Other observed liver aberrations included increased fatty vacuolation, congestion, structure disarray, increased size and number of melanin-macrophage centers, centrolobular fatty degeneration and necrosis, increased amounts of perivascular connective tissue, intercellular melanin deposits, and hepatocellular hypertrophy often associated with the presence of bizarre nuclei and/or multiple nucleoli. Livers evidencing microscopic lesions were usually discolored. Livers containing hepatomas were often mottled yellow or tan and brown; occasionally, hepatomas were visible as tan or white nodules. Although the cause(s) of the liver abnormalities has not been conclusively identified, chemical analyses of Duwamish River English sole have detected polychlorinated biphenyl (PCB) levels of about 1.5 ppm (dry wt) in total body tissue. Many of the above-mentioned abnormalities, with the exception of hepatomas, have been observed in fish exposed to PCB's."}
{"id": "PMID:206711", "title": "Effect of a mouse mammary tumor virus-derived protein vaccine on primary tumor development in mice.", "content": "The vaccines used in this study were derived from purified murine mammary tumor virus (MuMTV) preparations. Approximately 60% of the protein fractions consisted of the major viral membrane glycoprotein gp52. Inoculation sc of 10 microgram MuMTV-S-derived vaccine significantly delayed the appearance of primary mammary tumors in GR and BALB/cfC3H mice (strains with high incidences of mammary cancer); in BALB/c and C3Hf mice, which have a moderate tumor incidence at an advanced age, this treatment resulted in a slight and substantial acceleration, respectively, of primary tumor development. The induced cellular immune reactivity for vaccination, as measured with the in vivo Winn test and the in vitro leukocyte adherence inhibition assay, was strongest in the GR strain as compared to the BALB/c strain. The titer of antibodies to tumor cells, as estimated by membrane immunofluorescence, was also higher in the GR strain. In BALB/cfC3H mice, the influence of different vaccination schemes with an MuMTV-O-derived protein vaccine on primary tumor development was studied. Before sc injection, the vaccine was precipitated on alum. A dose of 10 microgram vaccine resulted in a 61% decrease in tumor incidence. Two or five additional booster injections with 1 microgram protein vaccine had no beneficial effect, although the amount of antibody measured was increased after boosting.", "contents": "Effect of a mouse mammary tumor virus-derived protein vaccine on primary tumor development in mice. The vaccines used in this study were derived from purified murine mammary tumor virus (MuMTV) preparations. Approximately 60% of the protein fractions consisted of the major viral membrane glycoprotein gp52. Inoculation sc of 10 microgram MuMTV-S-derived vaccine significantly delayed the appearance of primary mammary tumors in GR and BALB/cfC3H mice (strains with high incidences of mammary cancer); in BALB/c and C3Hf mice, which have a moderate tumor incidence at an advanced age, this treatment resulted in a slight and substantial acceleration, respectively, of primary tumor development. The induced cellular immune reactivity for vaccination, as measured with the in vivo Winn test and the in vitro leukocyte adherence inhibition assay, was strongest in the GR strain as compared to the BALB/c strain. The titer of antibodies to tumor cells, as estimated by membrane immunofluorescence, was also higher in the GR strain. In BALB/cfC3H mice, the influence of different vaccination schemes with an MuMTV-O-derived protein vaccine on primary tumor development was studied. Before sc injection, the vaccine was precipitated on alum. A dose of 10 microgram vaccine resulted in a 61% decrease in tumor incidence. Two or five additional booster injections with 1 microgram protein vaccine had no beneficial effect, although the amount of antibody measured was increased after boosting."}
{"id": "PMID:206712", "title": "Genetic control of immune responses to Moloney leukemia virus in rats.", "content": "When BN and LEW rats were immunized with untreated or with inactivated Moloney murine leukemia virus (M-MuLV), BN rats produced high antibody responses to the p15, p30, and gp70 antigens of the virus, whereas LEW rats were low responders to these antigens. BN rats also exhibited a high response and LEW rats a low response when the two strains were immunized with purified p30. Studies of (LEW X BN)F1 and backcross rats suggested that factors associated with AgB exerted major influences on responses to antigens of M-MuLV and that other factors were also important. When other rat strains representing 5 AgB alleles were tested, some were high and some were low responders to M-MuLV, and responses to p15, p30, and gp70 were not always parallel. Since M-MuLV replication was greater in cells of BN rats than in cells of LEW rats, replication of M-MuLV may have influenced the levels of responses to some viral antigens. Control of virus replication appeared to be due to cell mechanisms rather than to the environment of the host.", "contents": "Genetic control of immune responses to Moloney leukemia virus in rats. When BN and LEW rats were immunized with untreated or with inactivated Moloney murine leukemia virus (M-MuLV), BN rats produced high antibody responses to the p15, p30, and gp70 antigens of the virus, whereas LEW rats were low responders to these antigens. BN rats also exhibited a high response and LEW rats a low response when the two strains were immunized with purified p30. Studies of (LEW X BN)F1 and backcross rats suggested that factors associated with AgB exerted major influences on responses to antigens of M-MuLV and that other factors were also important. When other rat strains representing 5 AgB alleles were tested, some were high and some were low responders to M-MuLV, and responses to p15, p30, and gp70 were not always parallel. Since M-MuLV replication was greater in cells of BN rats than in cells of LEW rats, replication of M-MuLV may have influenced the levels of responses to some viral antigens. Control of virus replication appeared to be due to cell mechanisms rather than to the environment of the host."}
{"id": "PMID:206713", "title": "Leukemogenicity of clonal isolates of murine leukemia viruses.", "content": "The leukemogenicity of three types of cloned, in vitro grown murine retroviruses was studied. Two Moloney virus clones caused leukemia, as did five clones of the B-tropic endogenous virus of BALB/c mice. Neither of two clones of N-tropic BALB/c virus caused leukemia in Fv-1n/n mice, and the viruses were not recoverable from the animals. The ability to induce leukemia therefore appeared to reside in the genome of at least certain nondefective murine retroviruses.", "contents": "Leukemogenicity of clonal isolates of murine leukemia viruses. The leukemogenicity of three types of cloned, in vitro grown murine retroviruses was studied. Two Moloney virus clones caused leukemia, as did five clones of the B-tropic endogenous virus of BALB/c mice. Neither of two clones of N-tropic BALB/c virus caused leukemia in Fv-1n/n mice, and the viruses were not recoverable from the animals. The ability to induce leukemia therefore appeared to reside in the genome of at least certain nondefective murine retroviruses."}
{"id": "PMID:206714", "title": "Lymphocytotoxic autoantibodies eluted from in vivo propagating sarcoma cells of mice.", "content": "Eluates of SEYF-a cells (from polyoma virus-induced sarcoma grown in A.BY mice) containing cytotoxic anti-SEYF-a antibodies mediated complement-dependent cytotoxicity of normal lymph node cells. Some lymphocytotoxicity was also mediated by sera of tumor-bearing mice, but the pattern of cytotoxicity was different from that exhibited by tumor eluates. The titer of lymphocytotoxic antibodies in the serum was lower than the titer of anti-SEYF-a antibodies, whereas eluates exhibited similar titers toward both target cells. These results indicated that tumor cells selectively absorbed the lymphocytotoxic antibodies from the serum. Tumor eluates had cytotoxic activity also against thymocytes, splenocytes, and even bone marrow cells. The strain distribution of sensitive thymocytes to the antibodies present in eluates indicated that Thy 1 was not involved. Unfractionated eluates as well as IgG fractions isolated from eluates were active.", "contents": "Lymphocytotoxic autoantibodies eluted from in vivo propagating sarcoma cells of mice. Eluates of SEYF-a cells (from polyoma virus-induced sarcoma grown in A.BY mice) containing cytotoxic anti-SEYF-a antibodies mediated complement-dependent cytotoxicity of normal lymph node cells. Some lymphocytotoxicity was also mediated by sera of tumor-bearing mice, but the pattern of cytotoxicity was different from that exhibited by tumor eluates. The titer of lymphocytotoxic antibodies in the serum was lower than the titer of anti-SEYF-a antibodies, whereas eluates exhibited similar titers toward both target cells. These results indicated that tumor cells selectively absorbed the lymphocytotoxic antibodies from the serum. Tumor eluates had cytotoxic activity also against thymocytes, splenocytes, and even bone marrow cells. The strain distribution of sensitive thymocytes to the antibodies present in eluates indicated that Thy 1 was not involved. Unfractionated eluates as well as IgG fractions isolated from eluates were active."}
{"id": "PMID:206715", "title": "Observations on hepato-cellular carcinoma in the Sudan.", "content": "The clinical and histopathological features of hepato-cellular carcinoma in 24 Sudanese patients seen in Khartoum Civil Hospital in a 4 year period are described. The tumour represented 1.97 per cent of total medical admissions and constituted 40 per cent of all malignancies seen. The age range was 30 to 88 with a mean age of 54 years. The male:female ratio was 6:1. A regional variation was apparent and is possible that the disease is more common in the Western Sudan than in other parts of the country.", "contents": "Observations on hepato-cellular carcinoma in the Sudan. The clinical and histopathological features of hepato-cellular carcinoma in 24 Sudanese patients seen in Khartoum Civil Hospital in a 4 year period are described. The tumour represented 1.97 per cent of total medical admissions and constituted 40 per cent of all malignancies seen. The age range was 30 to 88 with a mean age of 54 years. The male:female ratio was 6:1. A regional variation was apparent and is possible that the disease is more common in the Western Sudan than in other parts of the country."}
{"id": "PMID:206716", "title": "Recovery nystagmus.", "content": "Secondary nystagmus is frequently seen following cessation of prolonged unidirectional vestibular stimulation. It is explained on the basis of an adaptation during the application of the stimulus which leads to an apparent stimulus in the opposite direction when the stimulus is removed. The same phenomenon would be expected with vestibular disease when after a period of adaptation to the vestibular asymmetry, the affected ear recovers some or all of its function. The seondary nystagmus in this instance beats toward the affected ear and has been termed recovery nystagmus because it is generated by recovery of function. Two cases with recovery nystagmus following acute attacks of vertigo are presented.", "contents": "Recovery nystagmus. Secondary nystagmus is frequently seen following cessation of prolonged unidirectional vestibular stimulation. It is explained on the basis of an adaptation during the application of the stimulus which leads to an apparent stimulus in the opposite direction when the stimulus is removed. The same phenomenon would be expected with vestibular disease when after a period of adaptation to the vestibular asymmetry, the affected ear recovers some or all of its function. The seondary nystagmus in this instance beats toward the affected ear and has been termed recovery nystagmus because it is generated by recovery of function. Two cases with recovery nystagmus following acute attacks of vertigo are presented."}
{"id": "PMID:206717", "title": "Herpes simplex virus and human cytomegalovirus replication in WI-38 cells. III. Cytochemical localization of lysosomal enzymes in infected cells.", "content": "Cytochemical localization of the lysosomal enzymes acid phosphatase and arylsulfatase in cells infected by herpes simplex virus (HSV) or human cytomegalovirus (CMV) showed the following interactions between viruses and host cell lysosomes: (i) many enveloped progeny viruses were located within cytoplasmic vacuoles containing lysosomal enzyme activity; (ii) naked cytoplasmic capsids appeared to acquire an envelope by budding directly into lysosomes; and (iii) many of the cytoplasmic dense bodies that are characteristic of CMV-infected cells and are thought to represent noninfectious aggregates of CMV structural proteins (I. Sarov and I. Abady, Virology 66:464-473, 1975) also acquired a limiting membrane by budding into lysosomes. Autophagy of other cytoplasmic elements was not observed, suggesting that there is some specificity involved in the association of viral particles and CMV dense bodies with lysosomes. Despite the presence of potentially destructive hydrolases, there was little evidence of significant morphological damage to intralysosomal viruses, and high titers of infectious particles were released into the medium. It would therefore appear that significant levels of HSV and CMV infectivity normally persist even though many progeny particles are directly exposed to lysosomal enzymes.", "contents": "Herpes simplex virus and human cytomegalovirus replication in WI-38 cells. III. Cytochemical localization of lysosomal enzymes in infected cells. Cytochemical localization of the lysosomal enzymes acid phosphatase and arylsulfatase in cells infected by herpes simplex virus (HSV) or human cytomegalovirus (CMV) showed the following interactions between viruses and host cell lysosomes: (i) many enveloped progeny viruses were located within cytoplasmic vacuoles containing lysosomal enzyme activity; (ii) naked cytoplasmic capsids appeared to acquire an envelope by budding directly into lysosomes; and (iii) many of the cytoplasmic dense bodies that are characteristic of CMV-infected cells and are thought to represent noninfectious aggregates of CMV structural proteins (I. Sarov and I. Abady, Virology 66:464-473, 1975) also acquired a limiting membrane by budding into lysosomes. Autophagy of other cytoplasmic elements was not observed, suggesting that there is some specificity involved in the association of viral particles and CMV dense bodies with lysosomes. Despite the presence of potentially destructive hydrolases, there was little evidence of significant morphological damage to intralysosomal viruses, and high titers of infectious particles were released into the medium. It would therefore appear that significant levels of HSV and CMV infectivity normally persist even though many progeny particles are directly exposed to lysosomal enzymes."}
{"id": "PMID:206718", "title": "FBJ osteosarcoma virus in tissue culture. III. Isolation and characterization of non-virus-producing FBJ-transformed cells.", "content": "Hamster and rat cell lines have been established that have been transformed by FBJ murine sarcoma virus (FBJ-MuSV) but that do not produce virus. The hamster cell line originated from an osteosarcoma that appeared in a hamster inoculated at birth with an extract of a CFNo1 mouse FBJ-osteosarcoma. The rat cell line was obtained by transferring the FBJ-MuSV genome to normal rat kidney cells in the absence of the FBJ type C virus (FBJ-MuLV), which, usually in high concentration, accompanies the FBJ-MuSV. Both transformed hamster and rat cell lines contain the FBJ-MuSV genome, which can be rescued by ecotropic and xenotropic murine type C viruses. This rescued genome produces characteristic FBJ-MuSV foci in tissue culture and, in appropriate animal hosts, induces osteosarcomas typical of those induced by FBJ-MuSV. FBJ-MuSV was isolated originally from a parosteal osteosarcoma that occurred naturally in a mouse. Since there was no previous history of passage of the agent through any other animal species, these non-virus-producing hamster and rat cells transformed by FBJ-MuSV should be very helpful in molecular studies examining the origin of spontaneous sarcoma genomes in mice.", "contents": "FBJ osteosarcoma virus in tissue culture. III. Isolation and characterization of non-virus-producing FBJ-transformed cells. Hamster and rat cell lines have been established that have been transformed by FBJ murine sarcoma virus (FBJ-MuSV) but that do not produce virus. The hamster cell line originated from an osteosarcoma that appeared in a hamster inoculated at birth with an extract of a CFNo1 mouse FBJ-osteosarcoma. The rat cell line was obtained by transferring the FBJ-MuSV genome to normal rat kidney cells in the absence of the FBJ type C virus (FBJ-MuLV), which, usually in high concentration, accompanies the FBJ-MuSV. Both transformed hamster and rat cell lines contain the FBJ-MuSV genome, which can be rescued by ecotropic and xenotropic murine type C viruses. This rescued genome produces characteristic FBJ-MuSV foci in tissue culture and, in appropriate animal hosts, induces osteosarcomas typical of those induced by FBJ-MuSV. FBJ-MuSV was isolated originally from a parosteal osteosarcoma that occurred naturally in a mouse. Since there was no previous history of passage of the agent through any other animal species, these non-virus-producing hamster and rat cells transformed by FBJ-MuSV should be very helpful in molecular studies examining the origin of spontaneous sarcoma genomes in mice."}
{"id": "PMID:206719", "title": "Assembly of viral membranes: nature of the association of vesicular stomatitis virus proteins to membranes.", "content": "To explore the interaction of vesicular stomatitis virus (VSV) proteins with cellular membranes, we have isolated membranes from infected cells that have been radioactively pulse-labeled. We have found conditions of isolation that result in membrane preparation which contain primarily the VSV membrane protein (M) and glycoprotein (G). Both of these proteins are very firmly attached to membranes: conditions known to release peripherally associated membrane proteins from membranes (S. Razin, Biochim, Biophys. Acta 265:241-246, 1972; S. J. Singer, Annu. Rev. Biochem. 43:805-826, 1974; S. J. Singer and G. L. Nicholson,  Science 175:720-731, 1972) are ineffective in detaching either the G or the M protein. The results of trypsin digestion of these membrane fractions suggest that the M protein resides primarily on one side, the cytoplasmic side of cellular membranes, whereas the glycoprotein has been transported to the lumen of the membrane vesicle. However, we present evidence that the glycoprotein is transmembranal and that approximately 3,000 daltons of one end of the molecule is on the cytoplasmic side of the membrane. We have also found that undenatured VSV M protein contains  a trypsin-resistant core with a molecular weight of 22,000. This region of the M protein is trypsin-resistant regardless of its association with membranes.", "contents": "Assembly of viral membranes: nature of the association of vesicular stomatitis virus proteins to membranes. To explore the interaction of vesicular stomatitis virus (VSV) proteins with cellular membranes, we have isolated membranes from infected cells that have been radioactively pulse-labeled. We have found conditions of isolation that result in membrane preparation which contain primarily the VSV membrane protein (M) and glycoprotein (G). Both of these proteins are very firmly attached to membranes: conditions known to release peripherally associated membrane proteins from membranes (S. Razin, Biochim, Biophys. Acta 265:241-246, 1972; S. J. Singer, Annu. Rev. Biochem. 43:805-826, 1974; S. J. Singer and G. L. Nicholson,  Science 175:720-731, 1972) are ineffective in detaching either the G or the M protein. The results of trypsin digestion of these membrane fractions suggest that the M protein resides primarily on one side, the cytoplasmic side of cellular membranes, whereas the glycoprotein has been transported to the lumen of the membrane vesicle. However, we present evidence that the glycoprotein is transmembranal and that approximately 3,000 daltons of one end of the molecule is on the cytoplasmic side of the membrane. We have also found that undenatured VSV M protein contains  a trypsin-resistant core with a molecular weight of 22,000. This region of the M protein is trypsin-resistant regardless of its association with membranes."}
{"id": "PMID:206720", "title": "Effects of 2'-deoxy-2'-azidocytidine on polyoma virus DNA replication: evidence for rolling circle-type mechanism.", "content": "Rolling circle-type molecules were found in polyoma virus-infected cells after inhibition of DNA synthesis with 2'-deoxy-2'-azidocytidine. The circular DNA molecules were always relaxed and of polyoma length. Most of the attached tails were less than two times the length of the polyoma genome, but tails with a length of up to 4.75 times the genome were also found. After cleavage of the total pool of replicating molecules with either endo R.EcoRI or endo R.BamI, Y-shaped molecules with replicated portions of various lengths were generated from rolling circle-type molecules. Moreover, after cleavage, Y-shaped molecules with three unequal arms were found, which could be explained as derived from the tail in rolling circle-type molecules starting from the normal origin, i.e., 29% from the endo R.EcoRI cleavage site. Rolling circle-type molecules were also found during a normal, noninhibited infection cycle. In such cells, a relatively higher frequency of rolling circle-type molecules was observed late during infection. Compared with control cultures, cultures inhibited with 2'-deoxy-2'-azidocytidine showed a greater amount of rolling circle-type molecules relative to normal replicative intermediates. 2'-Deoxy-2'-azidocytidine has previously been shown to inhibit the initiation of new rounds of replication; thus, the result obtained here indicates that a rolling circle-type mechanism is independent of the reinitiation of DNA synthesis.", "contents": "Effects of 2'-deoxy-2'-azidocytidine on polyoma virus DNA replication: evidence for rolling circle-type mechanism. Rolling circle-type molecules were found in polyoma virus-infected cells after inhibition of DNA synthesis with 2'-deoxy-2'-azidocytidine. The circular DNA molecules were always relaxed and of polyoma length. Most of the attached tails were less than two times the length of the polyoma genome, but tails with a length of up to 4.75 times the genome were also found. After cleavage of the total pool of replicating molecules with either endo R.EcoRI or endo R.BamI, Y-shaped molecules with replicated portions of various lengths were generated from rolling circle-type molecules. Moreover, after cleavage, Y-shaped molecules with three unequal arms were found, which could be explained as derived from the tail in rolling circle-type molecules starting from the normal origin, i.e., 29% from the endo R.EcoRI cleavage site. Rolling circle-type molecules were also found during a normal, noninhibited infection cycle. In such cells, a relatively higher frequency of rolling circle-type molecules was observed late during infection. Compared with control cultures, cultures inhibited with 2'-deoxy-2'-azidocytidine showed a greater amount of rolling circle-type molecules relative to normal replicative intermediates. 2'-Deoxy-2'-azidocytidine has previously been shown to inhibit the initiation of new rounds of replication; thus, the result obtained here indicates that a rolling circle-type mechanism is independent of the reinitiation of DNA synthesis."}
{"id": "PMID:206721", "title": "T1 oligonucleotide maps of N-, B-, and B leads to NB-tropic murine leukemia viruses derived from BALB/c.", "content": "We previously described and characterized RNase T1 RNA fingerprints of an N-, a B-, and five B leads to NB-tropic murine leukemia viruses derived from BALB/c mice (Faller and Hopkins, J. Virol. 23:188-195, 1977, and J. Virol. 24:609-617, 1977). These viruses share the majority of their large RNase T1-resistant oligonucleotides, but each possesses some \"unique\" oligonucleotides relative to the others. We have ordered the large T1-resistant oligonucleotides of the N-, the B-, and one NB-tropic virus relative to the 3' end of their genomes to obtain oligonucleotide maps. These maps indicate that (i) the large T1 oligonucleotides shared by the N-, B-, and NB-tropic viruses probably occupy the same relative positions on their genomes; (ii) the 14 T1 oligonucleotides that differ between the N- and B-tropic viruses are derived from regions scattered along the genomes;  and (iii) an oligonucleotide that is present in five NB-tropic viruses but not in their B-tropic virus progenitors lies toward the 5' end of the NB-tropic virus oligonucleotide map.", "contents": "T1 oligonucleotide maps of N-, B-, and B leads to NB-tropic murine leukemia viruses derived from BALB/c. We previously described and characterized RNase T1 RNA fingerprints of an N-, a B-, and five B leads to NB-tropic murine leukemia viruses derived from BALB/c mice (Faller and Hopkins, J. Virol. 23:188-195, 1977, and J. Virol. 24:609-617, 1977). These viruses share the majority of their large RNase T1-resistant oligonucleotides, but each possesses some \"unique\" oligonucleotides relative to the others. We have ordered the large T1-resistant oligonucleotides of the N-, the B-, and one NB-tropic virus relative to the 3' end of their genomes to obtain oligonucleotide maps. These maps indicate that (i) the large T1 oligonucleotides shared by the N-, B-, and NB-tropic viruses probably occupy the same relative positions on their genomes; (ii) the 14 T1 oligonucleotides that differ between the N- and B-tropic viruses are derived from regions scattered along the genomes;  and (iii) an oligonucleotide that is present in five NB-tropic viruses but not in their B-tropic virus progenitors lies toward the 5' end of the NB-tropic virus oligonucleotide map."}
{"id": "PMID:206722", "title": "T1 oligonucleotides that segregate with tropism and with properties of gp70 in recombinants between N- and B-tropic murine leukemia viruses.", "content": "We have analyzed large RNase T1-resistant oligonucleotides derived from the genomes of 16 recombinants between N- and B-tropic murine leukemia viruses of BALB/c. The parental viruses, designated SP-N and LP-B, differ in several phenotypic or biochemically defined properties: N- or B-tropism; XC plaque morphology, electrophoretic mobility of three virion proteins (p15, p30, and gp70); ability to induce GIX antigen on infected cells; presence of 6 to 8 (out of 36 to 38 analyzable) large T1 oligonucleotides. One SP-N-specific T1 oligonucleotide was inherited by all 16 N-tropic recombinants and, thus, appears to be linked to N-tropism. This oligonucleotide lies in the 5' third of the oligonucleotide map of SP-N. One LP-B-specific T1 oligonucleotide was inherited by all 11 recombinants whose gp70  has an electrophoretic mobility like that of LP-B gp70 and that, like LP-B, fail to induce GIX antigen. This oligonucleotide lies in the 3' third of the oligonucleotide map of LP-B.", "contents": "T1 oligonucleotides that segregate with tropism and with properties of gp70 in recombinants between N- and B-tropic murine leukemia viruses. We have analyzed large RNase T1-resistant oligonucleotides derived from the genomes of 16 recombinants between N- and B-tropic murine leukemia viruses of BALB/c. The parental viruses, designated SP-N and LP-B, differ in several phenotypic or biochemically defined properties: N- or B-tropism; XC plaque morphology, electrophoretic mobility of three virion proteins (p15, p30, and gp70); ability to induce GIX antigen on infected cells; presence of 6 to 8 (out of 36 to 38 analyzable) large T1 oligonucleotides. One SP-N-specific T1 oligonucleotide was inherited by all 16 N-tropic recombinants and, thus, appears to be linked to N-tropism. This oligonucleotide lies in the 5' third of the oligonucleotide map of SP-N. One LP-B-specific T1 oligonucleotide was inherited by all 11 recombinants whose gp70  has an electrophoretic mobility like that of LP-B gp70 and that, like LP-B, fail to induce GIX antigen. This oligonucleotide lies in the 3' third of the oligonucleotide map of LP-B."}
{"id": "PMID:206723", "title": "Bovine and ovine leukemia viruses. I. Characterization of viral antigens.", "content": "A comparative study on several virus-specific antigens of bovine and ovine leukemia viruses is presented. In addition to the major immunologically reactive, nonglycosylated antigen p21, which has a molecular weight of 21,000, both viruses share two glycoproteins of apparent molecular weights of 60,000 (gp60) and 32,000 (gp32), respectively. Immunological cross-reaction suggests that ovine and bovine leukemia viruses are genetically highly related.", "contents": "Bovine and ovine leukemia viruses. I. Characterization of viral antigens. A comparative study on several virus-specific antigens of bovine and ovine leukemia viruses is presented. In addition to the major immunologically reactive, nonglycosylated antigen p21, which has a molecular weight of 21,000, both viruses share two glycoproteins of apparent molecular weights of 60,000 (gp60) and 32,000 (gp32), respectively. Immunological cross-reaction suggests that ovine and bovine leukemia viruses are genetically highly related."}
{"id": "PMID:206724", "title": "In vitro RNA transcription by the New Jersey serotype of vesicular stomatitis virus. I. Characterization of the mRNA species.", "content": "The in vitro RNA synthesis by the virion-associated RNA polymerase of vesicular stomatitis virus (VSV), New Jersey serotype, was compared with that of the serologically distinct Indiana serotype of VSV. The New Jersey serotype of VSV synthesized five distinct mRNA species in vitro, three of which were smaller than the corresponding species synthesized by the Indiana serotype of VSV. These included the mRNA's coding for the G, M, and NS proteins. By hybridization experiments, virtually no sequence homology was detected between the mRNA's of the two serotypes. Despite this lack of overall homology, the 12 to 18S mRNA species of both serotype contained a common 5'-terminal hexanucleotide sequence, G(5')ppp(5')A-A-C-A-G. The signicance of this finding in light of specific interactions between the two serotypes of VSV in vivo is discussed.", "contents": "In vitro RNA transcription by the New Jersey serotype of vesicular stomatitis virus. I. Characterization of the mRNA species. The in vitro RNA synthesis by the virion-associated RNA polymerase of vesicular stomatitis virus (VSV), New Jersey serotype, was compared with that of the serologically distinct Indiana serotype of VSV. The New Jersey serotype of VSV synthesized five distinct mRNA species in vitro, three of which were smaller than the corresponding species synthesized by the Indiana serotype of VSV. These included the mRNA's coding for the G, M, and NS proteins. By hybridization experiments, virtually no sequence homology was detected between the mRNA's of the two serotypes. Despite this lack of overall homology, the 12 to 18S mRNA species of both serotype contained a common 5'-terminal hexanucleotide sequence, G(5')ppp(5')A-A-C-A-G. The signicance of this finding in light of specific interactions between the two serotypes of VSV in vivo is discussed."}
{"id": "PMID:206725", "title": "In vitro RNA transcription by the New Jersey serotype of vesicular stomatitis virus. II. Characterization of the leader RNA.", "content": "The New Jersey serotype of vesicular stomatitis virus (VSV) was able to synthesize a small RNA (leader RNA) approximately 70 bases in length similar to the leader RNA synthesized in vitro by the genetically distinct Indiana serotype of VSV. Also, the New Jersey leader RNA contained the same 5'-terminal sequence, ppA-C-G, as the Indiana leader RNA and had a very similar base composition, with 42% AMP, 16% CMP, 18.6% GMP, and 23.4% UMP. The 3'-terminal sequence of the VSV New Jersey genome RNA was detemined and found to contain the sequence- Py-G-UOH, again the same as that of the Indiana serotype of VSV. Evidence that the New Jersey leader RNA is transcribed from the 3' end of the genome RNA was obtained from the fact that it can protect the 3'-terminal base of [3H]borohydride-labeled New Jersey genome RNA from RNase digestion. Although the New Jersey and Indiana leader RNAs were similar in many respects, they were unable to form RNase-resistant hybrids when annealed to heterologous genome RNA.", "contents": "In vitro RNA transcription by the New Jersey serotype of vesicular stomatitis virus. II. Characterization of the leader RNA. The New Jersey serotype of vesicular stomatitis virus (VSV) was able to synthesize a small RNA (leader RNA) approximately 70 bases in length similar to the leader RNA synthesized in vitro by the genetically distinct Indiana serotype of VSV. Also, the New Jersey leader RNA contained the same 5'-terminal sequence, ppA-C-G, as the Indiana leader RNA and had a very similar base composition, with 42% AMP, 16% CMP, 18.6% GMP, and 23.4% UMP. The 3'-terminal sequence of the VSV New Jersey genome RNA was detemined and found to contain the sequence- Py-G-UOH, again the same as that of the Indiana serotype of VSV. Evidence that the New Jersey leader RNA is transcribed from the 3' end of the genome RNA was obtained from the fact that it can protect the 3'-terminal base of [3H]borohydride-labeled New Jersey genome RNA from RNase digestion. Although the New Jersey and Indiana leader RNAs were similar in many respects, they were unable to form RNase-resistant hybrids when annealed to heterologous genome RNA."}
{"id": "PMID:206726", "title": "Enhanced infectivity of adenovirus type 2 DNA and a DNA-protein complex.", "content": "The infectivity of adenovirus type 2 DNA and a DNA-protein complex was studied in 293 cells, a human embryonic kidney cell line transformed by sheared adenovirus type 5 DNA, and in human KB cells. Adenovirus type 2 DNA was more infectious (up to about 40-fold) in 293 cells than in KB cells, whereas a DNA-protein complex (prepared by a rapid procedure) had about the same infectivity in both cell lines. These data may mean that a factor present in 293 cells (perhaps a viral-coded protein) enhances the infectivity of free viral DNA. The infectivity of DNA and the DNA-protein complex was increased up to fivefold by brief treatment of cell monolayers with 25% dimethyl sulfoxide after transfection. Under these conditions, (i) the infectivity of native adenovirus type 2 DNA ranged from 400 to 1,300 PFU/microgram of DNA in 293 cells and from about 9 to 14 PFU/microgram of DNA in KB cells, and (ii) the infectivity of the DNA-protein complex was 6 X 10(3)to 2 X 10(4) PFU/microgram in 293 cells and 1.4 X 10(4) to 1.6 X 10(4) PFU/microgram in KB cells.", "contents": "Enhanced infectivity of adenovirus type 2 DNA and a DNA-protein complex. The infectivity of adenovirus type 2 DNA and a DNA-protein complex was studied in 293 cells, a human embryonic kidney cell line transformed by sheared adenovirus type 5 DNA, and in human KB cells. Adenovirus type 2 DNA was more infectious (up to about 40-fold) in 293 cells than in KB cells, whereas a DNA-protein complex (prepared by a rapid procedure) had about the same infectivity in both cell lines. These data may mean that a factor present in 293 cells (perhaps a viral-coded protein) enhances the infectivity of free viral DNA. The infectivity of DNA and the DNA-protein complex was increased up to fivefold by brief treatment of cell monolayers with 25% dimethyl sulfoxide after transfection. Under these conditions, (i) the infectivity of native adenovirus type 2 DNA ranged from 400 to 1,300 PFU/microgram of DNA in 293 cells and from about 9 to 14 PFU/microgram of DNA in KB cells, and (ii) the infectivity of the DNA-protein complex was 6 X 10(3)to 2 X 10(4) PFU/microgram in 293 cells and 1.4 X 10(4) to 1.6 X 10(4) PFU/microgram in KB cells."}
{"id": "PMID:206727", "title": "Biochemical transformation of mouse cells by herpes simplex virus type 2: enhancement by means of low-level photodynamic treatment.", "content": "The biochemical transformation of thymidine kinase-deficient cells by UV-inactivated herpes simplex virus is enhanced by low-level photodynamic treatment of the infected cells. At the concentration of proflavine used, the virus was not inactivated and both virus and cellular DNA syntheses were only marginally inhibited. The observed enhancement of the transfer of a virus gene to the cell genome suggests a possible cocarcinogenic role for photodynamically active dyes at very low concentrations.", "contents": "Biochemical transformation of mouse cells by herpes simplex virus type 2: enhancement by means of low-level photodynamic treatment. The biochemical transformation of thymidine kinase-deficient cells by UV-inactivated herpes simplex virus is enhanced by low-level photodynamic treatment of the infected cells. At the concentration of proflavine used, the virus was not inactivated and both virus and cellular DNA syntheses were only marginally inhibited. The observed enhancement of the transfer of a virus gene to the cell genome suggests a possible cocarcinogenic role for photodynamically active dyes at very low concentrations."}
{"id": "PMID:206728", "title": "Epstein-Barr virus-associated thymidine kinase.", "content": "Superinfection of Raji cells with Epstein-Barr virus induced a new thymidine kinase that was distinguishable from both adult and fetal kinases of the host cell by discontinuous electrophoresis on polyacrylamide gels and glycerol gradients.", "contents": "Epstein-Barr virus-associated thymidine kinase. Superinfection of Raji cells with Epstein-Barr virus induced a new thymidine kinase that was distinguishable from both adult and fetal kinases of the host cell by discontinuous electrophoresis on polyacrylamide gels and glycerol gradients."}
{"id": "PMID:206729", "title": "Biochemical characterization of the amphotropic group of murine leukemia viruses.", "content": "The recently described amphotropic group of murine leukemia viruses constitutes a distinct biological group, differing from the ecotropic and xenotropic groups in host range, cross interference, and serological reactivity. Viruses of this group have been detected only in wild mice from certain areas in California. By using a [3H]DNA probe synthesized in an endogenous reaction from detergent-lysed amphotropic virus (strain 1504-A), it was demonstrated that the amphotropic murine leukemia viruses are distinct biochemically, in that 20% of the viral genome sequences are not shared by AKR-type ecotropic or nay of three types of xenotropic murine leukemia virus tested. A subset of these amphotropic unique sequences, comprising one half of them, is present in the genome of wild mouse ecotropic viruses and in Moloney and Rauscher viruses as well. Sequences homologous to the entire genome of 1504-A amphotropic virus are present in the cellular DNA of all eight inbred mouse strains tested, as well as in wild Mus in Asia, in amounts varying from three to six complete viral genomes per haploid cell genome. Evidence is presented that at least 20% of the DNA sequences in both mouse- and mink-grown murine leukemia virus probes are of host-cell origin.", "contents": "Biochemical characterization of the amphotropic group of murine leukemia viruses. The recently described amphotropic group of murine leukemia viruses constitutes a distinct biological group, differing from the ecotropic and xenotropic groups in host range, cross interference, and serological reactivity. Viruses of this group have been detected only in wild mice from certain areas in California. By using a [3H]DNA probe synthesized in an endogenous reaction from detergent-lysed amphotropic virus (strain 1504-A), it was demonstrated that the amphotropic murine leukemia viruses are distinct biochemically, in that 20% of the viral genome sequences are not shared by AKR-type ecotropic or nay of three types of xenotropic murine leukemia virus tested. A subset of these amphotropic unique sequences, comprising one half of them, is present in the genome of wild mouse ecotropic viruses and in Moloney and Rauscher viruses as well. Sequences homologous to the entire genome of 1504-A amphotropic virus are present in the cellular DNA of all eight inbred mouse strains tested, as well as in wild Mus in Asia, in amounts varying from three to six complete viral genomes per haploid cell genome. Evidence is presented that at least 20% of the DNA sequences in both mouse- and mink-grown murine leukemia virus probes are of host-cell origin."}
{"id": "PMID:206730", "title": "Characterization and classification of virus particles associated with hepatitis A. I. Size, density, and sedimentation.", "content": "Virus-like particles were purified from stools of patients in an epidemic of hepatitis A in Germany. When reference MS-1 chimpanzee pre-inoculation and convalescent sera were used, the close serological relationship of the purified particles to well-known isolates of hepatitis A could be established. On the other hand, the physicochemical characteristics of the particles were determined in parallel to the characteristics of a marker parvovirus (LuIII) and a marker picornavirus (poliovirus type 2). It could be shown that the majority of the hepatitis A-associated particles band at 1.34 g/ml in CsCl and, like poliovirus, sediment at about 160S. In addition, a distinct hepatitis A antigen was observed, which banded at 1.305 g/ml and sedimented between 50 and 90S. A further component accumulated in the density range of between 1.38 and 1.44 g/ml. However, it seemed to be rather labile. Upon reisolation from CsCl and sedimentation in sucrose, it resolved into a 160S, a 90 to 100S, and a 50S form. The size of the 160S particles (27 to 29 nm) could be readily distinguished from that of the parvovirus (22 to 24 nm). It is concluded, therefore, that hepatitis A-associated virus particles are more likely to be classified with the picornaviruses than with the parvoviruses.", "contents": "Characterization and classification of virus particles associated with hepatitis A. I. Size, density, and sedimentation. Virus-like particles were purified from stools of patients in an epidemic of hepatitis A in Germany. When reference MS-1 chimpanzee pre-inoculation and convalescent sera were used, the close serological relationship of the purified particles to well-known isolates of hepatitis A could be established. On the other hand, the physicochemical characteristics of the particles were determined in parallel to the characteristics of a marker parvovirus (LuIII) and a marker picornavirus (poliovirus type 2). It could be shown that the majority of the hepatitis A-associated particles band at 1.34 g/ml in CsCl and, like poliovirus, sediment at about 160S. In addition, a distinct hepatitis A antigen was observed, which banded at 1.305 g/ml and sedimented between 50 and 90S. A further component accumulated in the density range of between 1.38 and 1.44 g/ml. However, it seemed to be rather labile. Upon reisolation from CsCl and sedimentation in sucrose, it resolved into a 160S, a 90 to 100S, and a 50S form. The size of the 160S particles (27 to 29 nm) could be readily distinguished from that of the parvovirus (22 to 24 nm). It is concluded, therefore, that hepatitis A-associated virus particles are more likely to be classified with the picornaviruses than with the parvoviruses."}
{"id": "PMID:206731", "title": "Characterization and classification of virus particles associated with hepatitis A. II. Type and configuration of nucleic acid.", "content": "Virus particles banding at 1.34 g/ml in CsCl and sedimenting at 160S in sucrose gradients were isolated from fecal specimens of patients suffering from hepatitis. In the presence of 4 M urea and about 90% formamide, these particles released linear nucleic acid molecules of the kinked appearance characteristic of single-stranded RNA or single-stranded DNA. They could be distinguished from the nucleic acid of phage lambda added to the preparation as a marker for double-stranded configuration. Experiments in which the virus particles under investigation were incubated at pH 12.9 at 50 degrees C for 30 min revealed that their nucleic acid molecules were hydrolyzed as readily as the RNA genome of poliovirus type 2 analyzed in parallel. Both the single-stranded DNA of phage phiX174 and that of parvovirus LuIII, however, proved unaffected by this treatment, and the double-stranded DNA of phage lambda was denatured to single-stranded molecules. It was concluded, therefore, that the virus of human hepatitis A contains a linear genome of single-stranded RNA and has to be classified with the picornaviruses.", "contents": "Characterization and classification of virus particles associated with hepatitis A. II. Type and configuration of nucleic acid. Virus particles banding at 1.34 g/ml in CsCl and sedimenting at 160S in sucrose gradients were isolated from fecal specimens of patients suffering from hepatitis. In the presence of 4 M urea and about 90% formamide, these particles released linear nucleic acid molecules of the kinked appearance characteristic of single-stranded RNA or single-stranded DNA. They could be distinguished from the nucleic acid of phage lambda added to the preparation as a marker for double-stranded configuration. Experiments in which the virus particles under investigation were incubated at pH 12.9 at 50 degrees C for 30 min revealed that their nucleic acid molecules were hydrolyzed as readily as the RNA genome of poliovirus type 2 analyzed in parallel. Both the single-stranded DNA of phage phiX174 and that of parvovirus LuIII, however, proved unaffected by this treatment, and the double-stranded DNA of phage lambda was denatured to single-stranded molecules. It was concluded, therefore, that the virus of human hepatitis A contains a linear genome of single-stranded RNA and has to be classified with the picornaviruses."}
{"id": "PMID:206732", "title": "Production of unintegrated mouse mammary tumor virus DNA in infected rat hepatoma cells is a secondary action of dexamethasone.", "content": "Dexamethasone, a synthetic glucocorticoid, selectively increased the rate of synthesis of mouse mammary tumor virus (MTV) RNA in clonal isolates of chronically infected rat hepatoma tissue culture cells. This hormonal effect occurred extremely rapidly and appeared to be mediated directly by the glucocorticoid-specific receptor protein. In addition to the viral RNA, unintegrated MTV DNA was also detected in these cells. Several lines of evidence are consistent with the idea that the unintegrated viral DNA is synthesized by reverse transcription of MTV RNA. (i) Unintegrated viral DNA accumulated only in the presence of dexamethasone and was produced with a time course that closely paralleled the increased accumulation of viral RNA. (ii) Density labeling of the viral DNA revealed that both strands were newly synthesized, implying a non-semiconservative mode of replication. (iii) Inhibitors of viral RNA synthesis prevented the appearance of unintegrated viral DNA. These data suggest that the production of unintegrated MTV DNA after dexamethasone treatment occurs as a secondary consequence of the hormonal induction of synthesis of viral RNA. In contrast to infected rat hepatoma cells, no unintegrated MTV DNA was detected in mouse mammary tumor cells or mouse lymphoma cells, despite the presence of high levels of viral RNA.", "contents": "Production of unintegrated mouse mammary tumor virus DNA in infected rat hepatoma cells is a secondary action of dexamethasone. Dexamethasone, a synthetic glucocorticoid, selectively increased the rate of synthesis of mouse mammary tumor virus (MTV) RNA in clonal isolates of chronically infected rat hepatoma tissue culture cells. This hormonal effect occurred extremely rapidly and appeared to be mediated directly by the glucocorticoid-specific receptor protein. In addition to the viral RNA, unintegrated MTV DNA was also detected in these cells. Several lines of evidence are consistent with the idea that the unintegrated viral DNA is synthesized by reverse transcription of MTV RNA. (i) Unintegrated viral DNA accumulated only in the presence of dexamethasone and was produced with a time course that closely paralleled the increased accumulation of viral RNA. (ii) Density labeling of the viral DNA revealed that both strands were newly synthesized, implying a non-semiconservative mode of replication. (iii) Inhibitors of viral RNA synthesis prevented the appearance of unintegrated viral DNA. These data suggest that the production of unintegrated MTV DNA after dexamethasone treatment occurs as a secondary consequence of the hormonal induction of synthesis of viral RNA. In contrast to infected rat hepatoma cells, no unintegrated MTV DNA was detected in mouse mammary tumor cells or mouse lymphoma cells, despite the presence of high levels of viral RNA."}
{"id": "PMID:206733", "title": "Attempted experimental transmission of pseudorabies virus to European starlings (Sturnus vulgaris).", "content": "Forty European starlings (Sturnus vulgaris) were inoculated orally with pseudorabies virus. Subsequent attempts to isolate the virus from feces, liver, lung and kidney of the birds were negative; antibody against the virus could not be detected in their serums.", "contents": "Attempted experimental transmission of pseudorabies virus to European starlings (Sturnus vulgaris). Forty European starlings (Sturnus vulgaris) were inoculated orally with pseudorabies virus. Subsequent attempts to isolate the virus from feces, liver, lung and kidney of the birds were negative; antibody against the virus could not be detected in their serums."}
{"id": "PMID:206734", "title": "Viral inclusions in raccoon liver cells.", "content": "Three young raccoons (Procyon lotor), two from Michigan and one from Arizona, died suddenly from acute infections. Intranuclear inclusion bodies and viral particles typical of herpesvirus were seen in liver cells from all three. Inclusions also were seen in the nuclei of endothelial cells in the lung, liver, glomeruli and reticuloendothelial cells of the spleen. The source of the infection was not determined, but possible transmission from other species could not be ruled out.", "contents": "Viral inclusions in raccoon liver cells. Three young raccoons (Procyon lotor), two from Michigan and one from Arizona, died suddenly from acute infections. Intranuclear inclusion bodies and viral particles typical of herpesvirus were seen in liver cells from all three. Inclusions also were seen in the nuclei of endothelial cells in the lung, liver, glomeruli and reticuloendothelial cells of the spleen. The source of the infection was not determined, but possible transmission from other species could not be ruled out."}
{"id": "PMID:206735", "title": "Oral polio vaccine. Effect of booster vaccination one to 14 years after primary series.", "content": "We studied the persistence of antibody after vaccination and the response to booster revaccination with trivalent oral polio vaccine (TOPV) administered at varied intervals after the primary series in a large group of children. Decline in antibody was related to intervals since last vaccination, and not to sex, age, age at primary vaccination, or type and number of previous administrations. Geometric mean titers of neutralizing antibody were 11.3 for type 1 and 8.0 for types 2 and 3 poliovirus when vaccine had been given within the previous year, declining to 3.2, 3.0, and 2.1 for types 1, 2, and 3 after nine years. Most children with an initial titer of 4 or less responded to revaccination with a fourfold or greater increase in titer of IgG. Geometric mean titers for all three types of polio dropped to this level when last TOPV administration had been five to six years or more.", "contents": "Oral polio vaccine. Effect of booster vaccination one to 14 years after primary series. We studied the persistence of antibody after vaccination and the response to booster revaccination with trivalent oral polio vaccine (TOPV) administered at varied intervals after the primary series in a large group of children. Decline in antibody was related to intervals since last vaccination, and not to sex, age, age at primary vaccination, or type and number of previous administrations. Geometric mean titers of neutralizing antibody were 11.3 for type 1 and 8.0 for types 2 and 3 poliovirus when vaccine had been given within the previous year, declining to 3.2, 3.0, and 2.1 for types 1, 2, and 3 after nine years. Most children with an initial titer of 4 or less responded to revaccination with a fourfold or greater increase in titer of IgG. Geometric mean titers for all three types of polio dropped to this level when last TOPV administration had been five to six years or more."}
{"id": "PMID:206736", "title": "Scintiangiography of hepatic masses in childhood.", "content": "Forty-three children with intrahepatic masses had technetium Tc 99m sulfur colloid hepatic scintigrams including scintiangiography. Hypervascularity occurred in nearly one third of the masses, but was limited to children with primary liver tumors including hepatomas, hepatoblastomas, hepatic adenomas, and cavernous hemangiomas. All metastases, abscesses, and hematomas were hypovascular. Routine inclusion of scintiangiography may allow separation of primary hypervascular liver tumors from other hypovascular masses whose static hepatic scintigrams are virtually identical.", "contents": "Scintiangiography of hepatic masses in childhood. Forty-three children with intrahepatic masses had technetium Tc 99m sulfur colloid hepatic scintigrams including scintiangiography. Hypervascularity occurred in nearly one third of the masses, but was limited to children with primary liver tumors including hepatomas, hepatoblastomas, hepatic adenomas, and cavernous hemangiomas. All metastases, abscesses, and hematomas were hypovascular. Routine inclusion of scintiangiography may allow separation of primary hypervascular liver tumors from other hypovascular masses whose static hepatic scintigrams are virtually identical."}
{"id": "PMID:206737", "title": "Carcinoma of the lung and cigarette smoking. Effect on serum ribonuclease activity.", "content": "Serum ribonuclease levels were determined in 54 patients with lung carcinoma, 74 long-term cigarette smokers, and 172 nonsmokers. The mean serum ribonuclease level was significantly higher in patients with lung carcinoma and long-term smokers compared with healthy nonsmokers (P less than .001). The serum ribonuclease activity level was not related to chronological age, sex, or race of the smoker or nonsmoker population. Forty (75%) of 53 patients with lung cancer and 49 (66%) of 74 smokers had elevated serum ribonuclease levels compared with 13 (7%) of 179 nonsmoker healthy controls (P less than .001). The highest incidence of elevation was noted in patients with epidermoid carcinoma (95%).", "contents": "Carcinoma of the lung and cigarette smoking. Effect on serum ribonuclease activity. Serum ribonuclease levels were determined in 54 patients with lung carcinoma, 74 long-term cigarette smokers, and 172 nonsmokers. The mean serum ribonuclease level was significantly higher in patients with lung carcinoma and long-term smokers compared with healthy nonsmokers (P less than .001). The serum ribonuclease activity level was not related to chronological age, sex, or race of the smoker or nonsmoker population. Forty (75%) of 53 patients with lung cancer and 49 (66%) of 74 smokers had elevated serum ribonuclease levels compared with 13 (7%) of 179 nonsmoker healthy controls (P less than .001). The highest incidence of elevation was noted in patients with epidermoid carcinoma (95%)."}
{"id": "PMID:206740", "title": "Studies on a dyslipoproteinemia in hemodialysis patients.", "content": "Grossly abnormal serum lipoprotein (Lp) profile which appeared as a broad-midband pattern (BMP) in PAG electrophoresis was detected in 67% of uremic patients maintained by prolonged hemodialysis therapy (hemodialysis patients). It was revealed that BMP was ascribed to the presence of a discrete series of Lps which were intermediate between beta-migrating LDL and pre-beta-migrating VLDL regarding buoyant density, Sf rate, chemical composition, and behavior in electrophoresis. The results in the present study indicate that the accumulation of these Lps, which may include the previously-known Lp species such as the intermediate-density Lp or the remnant particles, is taking place in hemodialysis patients.", "contents": "Studies on a dyslipoproteinemia in hemodialysis patients. Grossly abnormal serum lipoprotein (Lp) profile which appeared as a broad-midband pattern (BMP) in PAG electrophoresis was detected in 67% of uremic patients maintained by prolonged hemodialysis therapy (hemodialysis patients). It was revealed that BMP was ascribed to the presence of a discrete series of Lps which were intermediate between beta-migrating LDL and pre-beta-migrating VLDL regarding buoyant density, Sf rate, chemical composition, and behavior in electrophoresis. The results in the present study indicate that the accumulation of these Lps, which may include the previously-known Lp species such as the intermediate-density Lp or the remnant particles, is taking place in hemodialysis patients."}
{"id": "PMID:206749", "title": "Effects of intraventricularly administered polyamines spermidine and spermine on sleep-wakefulness cycles in rats.", "content": "Freely moving rats with chronically implanted electrodes were used and the electroencephalogram (EEG) from the occipital cortex and the dorsal hippocampus, the electromyogram (EMG) and the electrooculogram (EOG) were simultaneously recorded. The REM (rapid eye movement) sleep stage was significantly shortened without a marked change of the Non-REM sleep from the 24th to the 32nd hr following injection of 40 microgram of SPD. The waking stage significantly increased, and the Non-REM sleep and REM sleep markedly decreased immediately after the injection of 40 microgram of SPM to the 8th, and from the 24th to the 32nd hr. The amount of total sleep significantly shortened from the 72nd to the 80th hr following injection of 40 microgram of SPD. The administration of 40 microgram of SPM significantly reduced the amount of total sleep in every period measured  for 8 hr. Marked change was observed from the 24th to the 32nd hr following injection of 100 microgram of PUT, and Non-REM sleep and total sleep produced a significant decrease. These results show that the intraventricular administration of polyamines including PUT inhibits the amount of normal sleep.", "contents": "Effects of intraventricularly administered polyamines spermidine and spermine on sleep-wakefulness cycles in rats. Freely moving rats with chronically implanted electrodes were used and the electroencephalogram (EEG) from the occipital cortex and the dorsal hippocampus, the electromyogram (EMG) and the electrooculogram (EOG) were simultaneously recorded. The REM (rapid eye movement) sleep stage was significantly shortened without a marked change of the Non-REM sleep from the 24th to the 32nd hr following injection of 40 microgram of SPD. The waking stage significantly increased, and the Non-REM sleep and REM sleep markedly decreased immediately after the injection of 40 microgram of SPM to the 8th, and from the 24th to the 32nd hr. The amount of total sleep significantly shortened from the 72nd to the 80th hr following injection of 40 microgram of SPD. The administration of 40 microgram of SPM significantly reduced the amount of total sleep in every period measured  for 8 hr. Marked change was observed from the 24th to the 32nd hr following injection of 100 microgram of PUT, and Non-REM sleep and total sleep produced a significant decrease. These results show that the intraventricular administration of polyamines including PUT inhibits the amount of normal sleep."}
{"id": "PMID:206750", "title": "Effect of enkephalin and substance P on sympathetic nerve transmission in mouse vas deferens.", "content": "Effect of methionine-, leucine-enkephalin (met-, leu-enkephalin) and substance P on the transmission in mouse vas deferens was studied. Both met- and leu-enkephalin inhibited electrically induced contraction of vas deferens at 10(-8)-10(7) M, met-enkephalin being 1.4 times more active than leu-enkephalin. Nalorphine (10(-6) M) antagonized these effects. Substance P (10(-9)-10(-7) M) had no effect on the contraction. Met- and leu-enkephalin (10(-7)-10(-5) M) decreased the high potassium induced [3H]-norepinephrine release from vas deferens, while substance P (10(-6) M) significantly increased it. Nalorphine (10(-5) M) reversed the inhibitory effect of met-enkephalin. These results indicate that these peptides modify the transmission of sympathetic nerve in mouse vas deferens.", "contents": "Effect of enkephalin and substance P on sympathetic nerve transmission in mouse vas deferens. Effect of methionine-, leucine-enkephalin (met-, leu-enkephalin) and substance P on the transmission in mouse vas deferens was studied. Both met- and leu-enkephalin inhibited electrically induced contraction of vas deferens at 10(-8)-10(7) M, met-enkephalin being 1.4 times more active than leu-enkephalin. Nalorphine (10(-6) M) antagonized these effects. Substance P (10(-9)-10(-7) M) had no effect on the contraction. Met- and leu-enkephalin (10(-7)-10(-5) M) decreased the high potassium induced [3H]-norepinephrine release from vas deferens, while substance P (10(-6) M) significantly increased it. Nalorphine (10(-5) M) reversed the inhibitory effect of met-enkephalin. These results indicate that these peptides modify the transmission of sympathetic nerve in mouse vas deferens."}
{"id": "PMID:206751", "title": "No evidence for involvement of dopaminergic receptors in the positive inotropic action of dopamine on the isolated rabbit papillary muscle.", "content": "Experiments were carried out on the isolated rabbit papillary muscle driven at 0.5 Hz in order to further elucidate the mechanism of the positive inotropic effect evoked by dopamine. The dose-response curve for dopamine was not affected by the antagonists pimozide (10(-6) M), yohimbine (10(-5) M) pindolol (3 x 10(-8) M) and phentolamine (10(-6) M) when these agents were given separately. Only the simultaneous administration of yohimbine plus pindolol and phentolamine plus pindolol, respectively, shifted the entire curve to the right. This shift was not further influenced by pimozide. Dopamine (10(-4) M) increased the cyclic AMP content of the papillary muscle by about 50%; this increase was not affected by pimozide, but was markedly elevated by yohimbine and completely depressed by pindolol. From the present results it is concluded, that dopamine produces its positive inotropic effect through stimulation of myocardial alpha-as well as beta-adrenoceptors to about the same degree; stimulation of specific dopaminergic receptors, however, is not involved. The stimulation of beta-adrenoceptors is accompanied by an increase of the cyclic AMP level, while that of alpha-adrenoceptors is not.", "contents": "No evidence for involvement of dopaminergic receptors in the positive inotropic action of dopamine on the isolated rabbit papillary muscle. Experiments were carried out on the isolated rabbit papillary muscle driven at 0.5 Hz in order to further elucidate the mechanism of the positive inotropic effect evoked by dopamine. The dose-response curve for dopamine was not affected by the antagonists pimozide (10(-6) M), yohimbine (10(-5) M) pindolol (3 x 10(-8) M) and phentolamine (10(-6) M) when these agents were given separately. Only the simultaneous administration of yohimbine plus pindolol and phentolamine plus pindolol, respectively, shifted the entire curve to the right. This shift was not further influenced by pimozide. Dopamine (10(-4) M) increased the cyclic AMP content of the papillary muscle by about 50%; this increase was not affected by pimozide, but was markedly elevated by yohimbine and completely depressed by pindolol. From the present results it is concluded, that dopamine produces its positive inotropic effect through stimulation of myocardial alpha-as well as beta-adrenoceptors to about the same degree; stimulation of specific dopaminergic receptors, however, is not involved. The stimulation of beta-adrenoceptors is accompanied by an increase of the cyclic AMP level, while that of alpha-adrenoceptors is not."}
{"id": "PMID:206752", "title": "Morphine-induced changes in cyclic AMP metabolism and protein kinase activity in the brain.", "content": "The effects of consecutive oral administration of morphine on the cyclic AMP synthesizing system and cyclic AMP dependent protein kinase activity in the cerebral cortex of mice were examined. The administration of morphine (2--4 weeks) induced an increase of the cyclic AMP formation by activating adenylate cyclase, whereas responses of the cyclic AMP synthesizing system to biogenic amines (norepinephrine, dopamine and histamine) added in vitro was found to be significantly attenuated in these animals. Cyclic AMP dependent protein kinase activity in the cerebral cortex was also increased following a consecutive oral administration of morphine. These changes in the activities of adenylate cyclase and protein kinase were found mainly in crude mitochondrial and/or synaptosomal fractions. Morphine induced decrease in the response of the cyclic AMP synthesizing system to biogenic amines was rapidly reversed, and a significant increase of the cyclic AMP formation in the presence of added norepinephrine compared with that found in morphinized animals was observed following the administration of levallorphan, a narcotic antagonist. On the other hand, the changes in adenylate cyclase and cyclic AMP dependent protein kinase activities were not affected significantly by levallorphan administration. These results suggest that alterations in activities of cyclic AMP synthesizing system and of cyclic AMP dependent protein kinase may be involved in processes of the formation of morphine dependence. Possible involvement of abrupt increments in the sensitivity of \"norepinephrine receptor-adenylate cyclase\" system and a subsequent increase in cerebral cyclic AMP is also suggested as a cause of morphine withdrawal syndrome.", "contents": "Morphine-induced changes in cyclic AMP metabolism and protein kinase activity in the brain. The effects of consecutive oral administration of morphine on the cyclic AMP synthesizing system and cyclic AMP dependent protein kinase activity in the cerebral cortex of mice were examined. The administration of morphine (2--4 weeks) induced an increase of the cyclic AMP formation by activating adenylate cyclase, whereas responses of the cyclic AMP synthesizing system to biogenic amines (norepinephrine, dopamine and histamine) added in vitro was found to be significantly attenuated in these animals. Cyclic AMP dependent protein kinase activity in the cerebral cortex was also increased following a consecutive oral administration of morphine. These changes in the activities of adenylate cyclase and protein kinase were found mainly in crude mitochondrial and/or synaptosomal fractions. Morphine induced decrease in the response of the cyclic AMP synthesizing system to biogenic amines was rapidly reversed, and a significant increase of the cyclic AMP formation in the presence of added norepinephrine compared with that found in morphinized animals was observed following the administration of levallorphan, a narcotic antagonist. On the other hand, the changes in adenylate cyclase and cyclic AMP dependent protein kinase activities were not affected significantly by levallorphan administration. These results suggest that alterations in activities of cyclic AMP synthesizing system and of cyclic AMP dependent protein kinase may be involved in processes of the formation of morphine dependence. Possible involvement of abrupt increments in the sensitivity of \"norepinephrine receptor-adenylate cyclase\" system and a subsequent increase in cerebral cyclic AMP is also suggested as a cause of morphine withdrawal syndrome."}
{"id": "PMID:206761", "title": "[Metastasis from the colon to the choroid (author's transl)].", "content": "Various investigators have concluded that metastatic carcinoma is the most common malignant tumor of the eye. In about 70% of all cases the primary site is breast or lung. Metastasis from the colon to the choroid is found very seldom. The clinical course in our case is described and the elevated fashion of the right eye's metastatic carcinoma is shown. Usually cancerous tissue in the choroid spreads and produces a rather flat, diffuse lesion. Problems in making the diagnose are discussed. In choroidal metastasis radiation should be attempted, for adequate vision can sometimes be maintained for the remaining time of the patient's life.", "contents": "[Metastasis from the colon to the choroid (author's transl)]. Various investigators have concluded that metastatic carcinoma is the most common malignant tumor of the eye. In about 70% of all cases the primary site is breast or lung. Metastasis from the colon to the choroid is found very seldom. The clinical course in our case is described and the elevated fashion of the right eye's metastatic carcinoma is shown. Usually cancerous tissue in the choroid spreads and produces a rather flat, diffuse lesion. Problems in making the diagnose are discussed. In choroidal metastasis radiation should be attempted, for adequate vision can sometimes be maintained for the remaining time of the patient's life."}
{"id": "PMID:206762", "title": "[Considerations on the meta-herpetic keratitis (author's transl)].", "content": "The meta-herpetic keratitis is clinically characterized by the occurrence of a parenchymatous keratitis due to iterative herpetic corneal wounds. The rupture of the Bowman membrane which makes such a deep wound possible is performed by an enzyme: collagenase. This parenchymatous keratitis is rarely due to an extension of the viral infection. Most often it has an immunologic origin. It is a disciform keratitis due to a viral allergy, or a polymorphic keratitis connected with a bacterial, often tubercular, origin. In this case, one always notices a characteristic sugar tongs like composite limbic vascularization. Recovery can only be obtained by a specific desensitization.", "contents": "[Considerations on the meta-herpetic keratitis (author's transl)]. The meta-herpetic keratitis is clinically characterized by the occurrence of a parenchymatous keratitis due to iterative herpetic corneal wounds. The rupture of the Bowman membrane which makes such a deep wound possible is performed by an enzyme: collagenase. This parenchymatous keratitis is rarely due to an extension of the viral infection. Most often it has an immunologic origin. It is a disciform keratitis due to a viral allergy, or a polymorphic keratitis connected with a bacterial, often tubercular, origin. In this case, one always notices a characteristic sugar tongs like composite limbic vascularization. Recovery can only be obtained by a specific desensitization."}
{"id": "PMID:206763", "title": "[Coronary heart disease in patients with primary type V hyperlipoproteinemia (author's transl)].", "content": "In two patients with primary Type V hyperlipoproteinemia with typical clinical features including recurrent bouts of abdominal pain a myocardial infarction was diagnosed. In both cases coronary angiography revealed a severe three vessel disease. The case reports demonstrate that the incidence of ischemic heart disease in patients with Type V hyperlipoproteinemia is higher than reported in the literature. In each case of severe abdominal pain, even in younger Type V patients, a myocardial infarction has to be excluded, In both patients a selective depression in the activity of lipoprotein lipase was found. The possible pathogenetic implication of this finding will be discussed.", "contents": "[Coronary heart disease in patients with primary type V hyperlipoproteinemia (author's transl)]. In two patients with primary Type V hyperlipoproteinemia with typical clinical features including recurrent bouts of abdominal pain a myocardial infarction was diagnosed. In both cases coronary angiography revealed a severe three vessel disease. The case reports demonstrate that the incidence of ischemic heart disease in patients with Type V hyperlipoproteinemia is higher than reported in the literature. In each case of severe abdominal pain, even in younger Type V patients, a myocardial infarction has to be excluded, In both patients a selective depression in the activity of lipoprotein lipase was found. The possible pathogenetic implication of this finding will be discussed."}
{"id": "PMID:206764", "title": "[On the ACTH-corticoid relation in essential hypertension in dependence of plasma-renin activity (PRA) (author's transl)].", "content": "Patients with essential hypertension were studied for the reaction of the hypophyseal-adrenal-system before and during insulin hypoglycemia test. We found in our results that the mean total corticoid levels in plasma of hypertensive patients with low or high PRA are significantly higher than control levels. In insulin hypoglycemia test the mean corticoid levels of patients with normal and high PRA do not differ from the mean levels found in normal individuals whereas hypertensive patients with low PRA have significant lower plasma corticoid levels. The mean baseline and hypoglycemia induced plasma ACTH levels of each group of hypertensive patients are higher than those of the controls. Patients with high PRA show the highest rise of mean plasma ACTH levels during hypoglycemia. These data suggest that the adrenal system of hypertensive patients produces less total corticoids; plasma ACTH levels of these patients therefore are higher than those of normal individuals.", "contents": "[On the ACTH-corticoid relation in essential hypertension in dependence of plasma-renin activity (PRA) (author's transl)]. Patients with essential hypertension were studied for the reaction of the hypophyseal-adrenal-system before and during insulin hypoglycemia test. We found in our results that the mean total corticoid levels in plasma of hypertensive patients with low or high PRA are significantly higher than control levels. In insulin hypoglycemia test the mean corticoid levels of patients with normal and high PRA do not differ from the mean levels found in normal individuals whereas hypertensive patients with low PRA have significant lower plasma corticoid levels. The mean baseline and hypoglycemia induced plasma ACTH levels of each group of hypertensive patients are higher than those of the controls. Patients with high PRA show the highest rise of mean plasma ACTH levels during hypoglycemia. These data suggest that the adrenal system of hypertensive patients produces less total corticoids; plasma ACTH levels of these patients therefore are higher than those of normal individuals."}
{"id": "PMID:206786", "title": "Outpatient aftercare as a factor in treatment outcome; a pilot study.", "content": "Outpatients receiving psychotherapy at the facility in which they had previously been inpatients were more likely to remain abstinent than were former inpatients receiving outpatient care elsewhere.", "contents": "Outpatient aftercare as a factor in treatment outcome; a pilot study. Outpatients receiving psychotherapy at the facility in which they had previously been inpatients were more likely to remain abstinent than were former inpatients receiving outpatient care elsewhere."}
{"id": "PMID:206787", "title": "Aftercare for alcoholics: services of community mental health centers.", "content": "Fewer than half of the patients hospitalized for alcoholism treatment received aftercare from a community mental health center, the variables significantly related to receipt of aftercare being number of previous hospitalizations and referral to the hospital by self or family rather than by a court.", "contents": "Aftercare for alcoholics: services of community mental health centers. Fewer than half of the patients hospitalized for alcoholism treatment received aftercare from a community mental health center, the variables significantly related to receipt of aftercare being number of previous hospitalizations and referral to the hospital by self or family rather than by a court."}
{"id": "PMID:206793", "title": "[Surgery of extensive glomus jugulare tumors (author's transl)].", "content": "Clinical and neuroradiological aspects of extensive glomus jugulare tumors are presented. Surgery of these tumors is based on their growth along the veins: caudally along the internal jugular vein, cranially along the sigmoid sinus and medially along the transbasilar veins up to the cavernosus sinus. The main problem in total removal of glomus jugulare tumors is the relieving of the internal carotid artery from the tumor, especially in its intrapyramidal part. It is well known that glomus jugulare tumors tend to bleed excessively during surgery. Therefore the branches of the external carotid artery and the transverse sinus are ligated at the beginning of the operation. To avoid infection from the Eustachian tube to the posterior fossa, to close the dural defect over the cerebellar hemisphere and to protect the internal carotid artery a pedicled flap of the sternocleidomastoid muscle, based cranially, is prepared and rotated upwards in the base of the skull. 9 cases of extensive glomus jugulare tumors are presented.", "contents": "[Surgery of extensive glomus jugulare tumors (author's transl)]. Clinical and neuroradiological aspects of extensive glomus jugulare tumors are presented. Surgery of these tumors is based on their growth along the veins: caudally along the internal jugular vein, cranially along the sigmoid sinus and medially along the transbasilar veins up to the cavernosus sinus. The main problem in total removal of glomus jugulare tumors is the relieving of the internal carotid artery from the tumor, especially in its intrapyramidal part. It is well known that glomus jugulare tumors tend to bleed excessively during surgery. Therefore the branches of the external carotid artery and the transverse sinus are ligated at the beginning of the operation. To avoid infection from the Eustachian tube to the posterior fossa, to close the dural defect over the cerebellar hemisphere and to protect the internal carotid artery a pedicled flap of the sternocleidomastoid muscle, based cranially, is prepared and rotated upwards in the base of the skull. 9 cases of extensive glomus jugulare tumors are presented."}
{"id": "PMID:206799", "title": "Cushing's syndrome due to adrenal adenoma with persistent diurnal cortisol secretory rhythm.", "content": "A 41-yr-old female with presumed Cushing's syndrome was found to have a diurnal cortisol rhythm characterized by low values of 8:00 a.m. and consistently high values at 4:00 p.m. and midnight. Hourly sampling of plasma cortisol over 24 hr confirmed this rhythm, as did measurement of urinary free cortisols in samples collected every 6 hr over 24 hr. Hypercortisolemia was not suppressed by 2 mg of dexamethasone given every 6 hr for 24 hr. The adrenal tissue was responsive to ACTH. Iodocholesterol scanning revealed unilateral activity, and the patient's syndrome was cured by resection of an adrenal adenoma. In this patient a diurnal cortisol secretory pattern was present due to the secretory activity of the adenoma. The cause of the abnormal but persistent diurnal pattern is unknown.", "contents": "Cushing's syndrome due to adrenal adenoma with persistent diurnal cortisol secretory rhythm. A 41-yr-old female with presumed Cushing's syndrome was found to have a diurnal cortisol rhythm characterized by low values of 8:00 a.m. and consistently high values at 4:00 p.m. and midnight. Hourly sampling of plasma cortisol over 24 hr confirmed this rhythm, as did measurement of urinary free cortisols in samples collected every 6 hr over 24 hr. Hypercortisolemia was not suppressed by 2 mg of dexamethasone given every 6 hr for 24 hr. The adrenal tissue was responsive to ACTH. Iodocholesterol scanning revealed unilateral activity, and the patient's syndrome was cured by resection of an adrenal adenoma. In this patient a diurnal cortisol secretory pattern was present due to the secretory activity of the adenoma. The cause of the abnormal but persistent diurnal pattern is unknown."}
{"id": "PMID:206800", "title": "Thiazide diuretics do not potentiate cAMP response to parathyroid hormone.", "content": "We evaluated the hypothesis that thiazide-induced hypercalcemia reflects potentiation of the cAMP response to parathyroid hormone (PTH) consequent to inhibition of phosphodiesterase in bone and kidney. A panel of thiazide diuretics did inhibit low-Km phosphodiesterase activity from bone homogenates. However, furosemide, a nonthiazide diuretic that does not promote calcium retention, was more potent a phosphodiesterase inhibitor than either chloro- or hydrochlorothiazide (CTZ, HCTZ). Thiazides did not influence basal or PTH-stimulated cAMP levels in incubated calvaria or renal cortical slices. Administration of CTZ or HCTZ to rats for 4 days did not affect basal cAMP, nor did such treatment potentiate the cAMP response in Calvaria to infusion of parathyroid extract in vivo. CTZ, HCTZ, and furosemide increased basal adenylate cyclase from renal cortex but did not affect PTH-stimulated activity. Adenylate cyclase from bone was not affected by thiazides but was inhibited by furosemide. Thiazide treatment potentiated the calcemic response to parathyroid extract in vivo but did not affect the calcemic response to dibutyryl cAMP. We conclude that potentiation of the cAMP response to PTH does not underlie the unique effects of thiazides on calcium metabolism.", "contents": "Thiazide diuretics do not potentiate cAMP response to parathyroid hormone. We evaluated the hypothesis that thiazide-induced hypercalcemia reflects potentiation of the cAMP response to parathyroid hormone (PTH) consequent to inhibition of phosphodiesterase in bone and kidney. A panel of thiazide diuretics did inhibit low-Km phosphodiesterase activity from bone homogenates. However, furosemide, a nonthiazide diuretic that does not promote calcium retention, was more potent a phosphodiesterase inhibitor than either chloro- or hydrochlorothiazide (CTZ, HCTZ). Thiazides did not influence basal or PTH-stimulated cAMP levels in incubated calvaria or renal cortical slices. Administration of CTZ or HCTZ to rats for 4 days did not affect basal cAMP, nor did such treatment potentiate the cAMP response in Calvaria to infusion of parathyroid extract in vivo. CTZ, HCTZ, and furosemide increased basal adenylate cyclase from renal cortex but did not affect PTH-stimulated activity. Adenylate cyclase from bone was not affected by thiazides but was inhibited by furosemide. Thiazide treatment potentiated the calcemic response to parathyroid extract in vivo but did not affect the calcemic response to dibutyryl cAMP. We conclude that potentiation of the cAMP response to PTH does not underlie the unique effects of thiazides on calcium metabolism."}
{"id": "PMID:206806", "title": "[Effect of histones on a change in the enzymatic activity of Escherichia coli and Staphylococcus aureus cells].", "content": "Histones have been found to interfere with the permeability of the cellular membranes of Escherichia coli and Staphylococcus aureus, this resulting in the liberation of 14C-amino acids, the UV-absorbing endogenous material, and the products of RNA degradation. Histones, particularly arginine-rich fractions, stimulated the RNAase activity of the bacteria. Histones inhibited the phosphatase activity of E. coli and stimulated that of Staphylococcus aureus. The ATPase activity of the cells increased upon contact with histones. These enzyme systems are presumed to be components of a mechanism whose activity increases upon the action on the cells of factors interfering with the permeability of the membranes so that low-molecular-weight compounds are liberated from the cells. It is possible that the RNAase, ATPase and phosphatase systems repair the pool of low-molecular-weight compounds, thus contributing to the survival of the bacteria.", "contents": "[Effect of histones on a change in the enzymatic activity of Escherichia coli and Staphylococcus aureus cells]. Histones have been found to interfere with the permeability of the cellular membranes of Escherichia coli and Staphylococcus aureus, this resulting in the liberation of 14C-amino acids, the UV-absorbing endogenous material, and the products of RNA degradation. Histones, particularly arginine-rich fractions, stimulated the RNAase activity of the bacteria. Histones inhibited the phosphatase activity of E. coli and stimulated that of Staphylococcus aureus. The ATPase activity of the cells increased upon contact with histones. These enzyme systems are presumed to be components of a mechanism whose activity increases upon the action on the cells of factors interfering with the permeability of the membranes so that low-molecular-weight compounds are liberated from the cells. It is possible that the RNAase, ATPase and phosphatase systems repair the pool of low-molecular-weight compounds, thus contributing to the survival of the bacteria."}
{"id": "PMID:206807", "title": "[Changes in the electron transport chain in Escherichia coli depending on the cultivation conditions and growth phase].", "content": "Changes in the electron transport chain of E. coli K-12 were studied as a function of the growth phase and the nature of a terminal electron acceptor in the growth medium. The content of flavins in the preparations of bacterial membranes hardly changed in all cases. The highest concentration of quinones was observed in the bacterial membranes at the stationary growth phase under anaerobic conditions of growth in the presence of nitrate. These membranes contained also the greatest amount of cytochrome beta1. The concentration of cytochrome alpha2 in all the membranes was low and varied among different preparations. All the membranes contained a CO-binding pigment whose content was maximal in the membranes of \"nitrate\" cells. The membranes of cells grown under aerobic conditions oxidized malate, apart from NADH and lactate, whereas the membranes of cells cultivated under anaerobic conditions in the presence of nitrate oxidized formiate. In most cases, the oxidase activity of the membranes of cells collected at the stationary growth phase was higher cf. the exponential phase.", "contents": "[Changes in the electron transport chain in Escherichia coli depending on the cultivation conditions and growth phase]. Changes in the electron transport chain of E. coli K-12 were studied as a function of the growth phase and the nature of a terminal electron acceptor in the growth medium. The content of flavins in the preparations of bacterial membranes hardly changed in all cases. The highest concentration of quinones was observed in the bacterial membranes at the stationary growth phase under anaerobic conditions of growth in the presence of nitrate. These membranes contained also the greatest amount of cytochrome beta1. The concentration of cytochrome alpha2 in all the membranes was low and varied among different preparations. All the membranes contained a CO-binding pigment whose content was maximal in the membranes of \"nitrate\" cells. The membranes of cells grown under aerobic conditions oxidized malate, apart from NADH and lactate, whereas the membranes of cells cultivated under anaerobic conditions in the presence of nitrate oxidized formiate. In most cases, the oxidase activity of the membranes of cells collected at the stationary growth phase was higher cf. the exponential phase."}
{"id": "PMID:206808", "title": "[Fatty acid makeup of Escherichia coli cells with repressed and derepressed phosphohydrolase biosynthesis].", "content": "Fatty acid composition of the cells of Escherchia coli wild strains K-10, and K-12 and the mutants of the regulatory genes for alkaline phosphatase was studied in conditions of repression and derepression of biosynthesis of phosphohydrolases. Derepression of phosphohydrolases was not accompanied with specific changes in fatty acid composition of the cells. An increase in the content of cyclopropanic acid in conditions of phosphorus deficiency and a decrease in the level of unsaturated fatty acids are related to deceleration of growth of the cells in these conditions.", "contents": "[Fatty acid makeup of Escherichia coli cells with repressed and derepressed phosphohydrolase biosynthesis]. Fatty acid composition of the cells of Escherchia coli wild strains K-10, and K-12 and the mutants of the regulatory genes for alkaline phosphatase was studied in conditions of repression and derepression of biosynthesis of phosphohydrolases. Derepression of phosphohydrolases was not accompanied with specific changes in fatty acid composition of the cells. An increase in the content of cyclopropanic acid in conditions of phosphorus deficiency and a decrease in the level of unsaturated fatty acids are related to deceleration of growth of the cells in these conditions."}
{"id": "PMID:206812", "title": "[Comparison of liposoluble and water-soluble contrast media in sialography].", "content": "Highly, averagely and lightly viscous contrast media most frequently used in radiography of the salivary glands have been compared. It is concluded that the preparation which has so far given the best results is liposoluble but averagely viscous and not too contrasting.", "contents": "[Comparison of liposoluble and water-soluble contrast media in sialography]. Highly, averagely and lightly viscous contrast media most frequently used in radiography of the salivary glands have been compared. It is concluded that the preparation which has so far given the best results is liposoluble but averagely viscous and not too contrasting."}
{"id": "PMID:206818", "title": "A kinetic analysis of glucokinase and glucose-6-P phosphatase in Dictyostelium.", "content": "Using a mathematical model of carbohydrate metabolism in Dictyostelium discoideum, the kinetic expressions describing the activities of glucokinase and glucose-6-P phosphatase have been analyzed. The constraints on the kinetic mechanisms and relative activities of these two enzymes were investigated by comparing computer simulations to experimental data. The results indicated that, (1) glucose-6-P is compartmentalized with respect to the enzymes involved in glucose-60P, trehalose and glycogen metabolism, (2) a differences of approximately 0.6 mM/min in maximum specific activity of glucokinase compared to glucose-6-P phosphatase is required in order for the model to produce end product carbohydrate levels consistent with those observed experimentally, (3) the Km of glucokinase for glucose strongly influences the steady state levels of glucose in the absence of external glucose, and (4) changing the order of product removal in the reaction catalyzed by glucose-6-P phosphatase influences the level of glycogen and trehalose.", "contents": "A kinetic analysis of glucokinase and glucose-6-P phosphatase in Dictyostelium. Using a mathematical model of carbohydrate metabolism in Dictyostelium discoideum, the kinetic expressions describing the activities of glucokinase and glucose-6-P phosphatase have been analyzed. The constraints on the kinetic mechanisms and relative activities of these two enzymes were investigated by comparing computer simulations to experimental data. The results indicated that, (1) glucose-6-P is compartmentalized with respect to the enzymes involved in glucose-60P, trehalose and glycogen metabolism, (2) a differences of approximately 0.6 mM/min in maximum specific activity of glucokinase compared to glucose-6-P phosphatase is required in order for the model to produce end product carbohydrate levels consistent with those observed experimentally, (3) the Km of glucokinase for glucose strongly influences the steady state levels of glucose in the absence of external glucose, and (4) changing the order of product removal in the reaction catalyzed by glucose-6-P phosphatase influences the level of glycogen and trehalose."}
{"id": "PMID:206819", "title": "The use of viable hepatocytes to study the hormonal control of glycogenolysis in the chicken.", "content": "The rapid isolation of high yields of parenchymal cells from chicken liver is described. Stringent tests of viability show that the isolated hepatocytes are both structurally and metabolically similar to those in intact liver. During incubation viability decreased and the significance of this change on the interpretation of metabolic experiments is discussed. Lactate was a much more effective gluconeogenic precursor than pyruvate even in the presence of additional reducing equivalents. Hepatocytes isolated from fed chickens produced glucose from glycogen degradation. Glycogenolysis was stimulated by glucagon, dibutyryl cyclic AMP and adrenaline. Half maximal glucagon effects were elicited by physiological concentrations of the hormone. Glucagon and dibutyryl cyclic AMP stimulated glucagon, dibutyryl cyclic AMP and adrenaline their action was not additive to that of adrenaline.", "contents": "The use of viable hepatocytes to study the hormonal control of glycogenolysis in the chicken. The rapid isolation of high yields of parenchymal cells from chicken liver is described. Stringent tests of viability show that the isolated hepatocytes are both structurally and metabolically similar to those in intact liver. During incubation viability decreased and the significance of this change on the interpretation of metabolic experiments is discussed. Lactate was a much more effective gluconeogenic precursor than pyruvate even in the presence of additional reducing equivalents. Hepatocytes isolated from fed chickens produced glucose from glycogen degradation. Glycogenolysis was stimulated by glucagon, dibutyryl cyclic AMP and adrenaline. Half maximal glucagon effects were elicited by physiological concentrations of the hormone. Glucagon and dibutyryl cyclic AMP stimulated glucagon, dibutyryl cyclic AMP and adrenaline their action was not additive to that of adrenaline."}
{"id": "PMID:206820", "title": "Periodicity and fragment size of DNA from mouse TLT hepatoma chromatin and chromatin fractions using endogenous and exogenous nucleases.", "content": "The action of micrococcal nuclease, DNase I and DNase II on mouse TLT hepatoma chromatin revealing the periodicity of its structure as visualized by denaturing and non-denaturing gel electrophoresis, was consistent with the action of these enzymes on other chromatins. Micrococcal nuclease showed a complex subnucleosome fragment pattern based on multiples of 10 base pairs with a prominant couplet at 140/160 base pairs and the absence of the 80 base pair fragment. This couplet of the core and minimal nucleosome fragments was conspicuously present in the mononucleosomes found in the 11S fractions of a glycerol gradient centrifugation. DNase I and II produced a fairly even distribution of a 10 base pair increasing series of fragments to about 180 base pairs, a pattern also repeated in the DNA of nucleosome glycerol-gradient fractions. In limited digestions by these nucleases multinucleosomic DNA fragments are pronounced. These fragment lengths are multiples of an estimated average repeat length of nucleosome DNA of 180 base pairs. The action of the endogenous Mg/Ca-stimulated endonuclease produced only limited cuts in the hepatoma chromatin resulting primarily in multi-nucleosomic DNA fragment lengths and only upon lengthy digestion limited subnucleosomic, 10-base-pair multiple fragments are produced. The putative euchromatin-enriched fractions (50-75S) of the glycerol gradient centrifugation of autodigested chromatin, similarly, contained primarily the multinucleosomic DNA fragment lengths. These results are consistent with our previous electron microscopic demonstration that autodigested chromatin as well as the putative euchromatin-enriched fractions were composed of multi-nucleosomic chromatin segments containing a full complement of histones.", "contents": "Periodicity and fragment size of DNA from mouse TLT hepatoma chromatin and chromatin fractions using endogenous and exogenous nucleases. The action of micrococcal nuclease, DNase I and DNase II on mouse TLT hepatoma chromatin revealing the periodicity of its structure as visualized by denaturing and non-denaturing gel electrophoresis, was consistent with the action of these enzymes on other chromatins. Micrococcal nuclease showed a complex subnucleosome fragment pattern based on multiples of 10 base pairs with a prominant couplet at 140/160 base pairs and the absence of the 80 base pair fragment. This couplet of the core and minimal nucleosome fragments was conspicuously present in the mononucleosomes found in the 11S fractions of a glycerol gradient centrifugation. DNase I and II produced a fairly even distribution of a 10 base pair increasing series of fragments to about 180 base pairs, a pattern also repeated in the DNA of nucleosome glycerol-gradient fractions. In limited digestions by these nucleases multinucleosomic DNA fragments are pronounced. These fragment lengths are multiples of an estimated average repeat length of nucleosome DNA of 180 base pairs. The action of the endogenous Mg/Ca-stimulated endonuclease produced only limited cuts in the hepatoma chromatin resulting primarily in multi-nucleosomic DNA fragment lengths and only upon lengthy digestion limited subnucleosomic, 10-base-pair multiple fragments are produced. The putative euchromatin-enriched fractions (50-75S) of the glycerol gradient centrifugation of autodigested chromatin, similarly, contained primarily the multinucleosomic DNA fragment lengths. These results are consistent with our previous electron microscopic demonstration that autodigested chromatin as well as the putative euchromatin-enriched fractions were composed of multi-nucleosomic chromatin segments containing a full complement of histones."}
{"id": "PMID:206822", "title": "[Circadian rhythm of cortisol under ACTH and dexamethasone therapy of convulsions in early childhood (BNS- and Lennox-syndrome) (author's transl)].", "content": "Convulsions in early childhood were treated successfully in a long term and high dosage regime with depot corticotrophin (80-120 IU/die) and dexamethasone (0.3 mg/kg/die). Depot-beta1-23corticotrophin stimulated, dexamethasone suppressed plasma cortisol levels, which, accordingly, ceased to show circadian rhythms. If dexamethasone was given alternately (every second day) and in a reduced dose (0.1 mg/kg) plasma cortisol levels increased, and if dosage was reduced again to 0.05 mg/kg cortisol levels showed circadian rhythms comparable to those before therapy. There was no disturbance of the hypothalamic--pituitary--adrenal system at the end of therapy. Considering experimental results in animals corticotrophin peptides and dexamethasone molecules might have a direct effect on the brain as far as cerebral convulsions are concerned. Because of serious side effects of steroids during treatment it seems to be worth while to try corticotrophin fragments, which had similar effects on the brain as beta1-24corticotrophin in animals, but without stimulating the adrenals.", "contents": "[Circadian rhythm of cortisol under ACTH and dexamethasone therapy of convulsions in early childhood (BNS- and Lennox-syndrome) (author's transl)]. Convulsions in early childhood were treated successfully in a long term and high dosage regime with depot corticotrophin (80-120 IU/die) and dexamethasone (0.3 mg/kg/die). Depot-beta1-23corticotrophin stimulated, dexamethasone suppressed plasma cortisol levels, which, accordingly, ceased to show circadian rhythms. If dexamethasone was given alternately (every second day) and in a reduced dose (0.1 mg/kg) plasma cortisol levels increased, and if dosage was reduced again to 0.05 mg/kg cortisol levels showed circadian rhythms comparable to those before therapy. There was no disturbance of the hypothalamic--pituitary--adrenal system at the end of therapy. Considering experimental results in animals corticotrophin peptides and dexamethasone molecules might have a direct effect on the brain as far as cerebral convulsions are concerned. Because of serious side effects of steroids during treatment it seems to be worth while to try corticotrophin fragments, which had similar effects on the brain as beta1-24corticotrophin in animals, but without stimulating the adrenals."}
{"id": "PMID:206821", "title": "[Physico-chemical properties of the RNA of Sendai virus. III. Interaction with proflavin].", "content": "The binding isotherms of the Sendai virus single- and double-stranded RNA-proflavine complexes have been studied. The existence of two regions on the binding curves, corresponding to two subtypes of the strong complex (I1 and I2) has been demonstrated. The association constants and the numbers of binding sites for both subtypes were determined as a function of ionic strength. Both of the single- and for the double-stranded RNA the association constant for I1 complex were higher than those for I2 complex under all ionic strengths conditions. For the double-stranded RNA the variation of the ionic strength is more importance in case of the I1 complex formation. The total number of binding sites increases with a decrease of ionic strength. At low ionic strength (10(-4) M NaCl) the number of binding sites for single- and double-stranded RNA is practically the same and is equal to the number of binding sites for DNA at high ionic strength (1 molecule of proflavine per 3 nucleotides pairs). The heat denaturation of the RNA-proflavine complexes under different ionic conditions has been also investigated. The melting curves for double-stranded RNA-proflavine complex had two waves at high and low ionic strengths. For the single-stranded RNA the high temperature wave occured only at the high ionic strength. The dependence of heat denaturation of single-stranded RNA on ionic strength was examined for the evaluation of RNA structure. In these experiments a significant decrease of the width of melting interval under low ionic strength conditions was observed. It may reflect the existance in the RNA molecule of long helical regions. The occurence of such structures is likely to be responsible for an increase in the number of binding sites at low ionic strength and also for the appearance of the second wave on the melting curves of the single-stranded RNA-proflavine complexes at high ionic strength.", "contents": "[Physico-chemical properties of the RNA of Sendai virus. III. Interaction with proflavin]. The binding isotherms of the Sendai virus single- and double-stranded RNA-proflavine complexes have been studied. The existence of two regions on the binding curves, corresponding to two subtypes of the strong complex (I1 and I2) has been demonstrated. The association constants and the numbers of binding sites for both subtypes were determined as a function of ionic strength. Both of the single- and for the double-stranded RNA the association constant for I1 complex were higher than those for I2 complex under all ionic strengths conditions. For the double-stranded RNA the variation of the ionic strength is more importance in case of the I1 complex formation. The total number of binding sites increases with a decrease of ionic strength. At low ionic strength (10(-4) M NaCl) the number of binding sites for single- and double-stranded RNA is practically the same and is equal to the number of binding sites for DNA at high ionic strength (1 molecule of proflavine per 3 nucleotides pairs). The heat denaturation of the RNA-proflavine complexes under different ionic conditions has been also investigated. The melting curves for double-stranded RNA-proflavine complex had two waves at high and low ionic strengths. For the single-stranded RNA the high temperature wave occured only at the high ionic strength. The dependence of heat denaturation of single-stranded RNA on ionic strength was examined for the evaluation of RNA structure. In these experiments a significant decrease of the width of melting interval under low ionic strength conditions was observed. It may reflect the existance in the RNA molecule of long helical regions. The occurence of such structures is likely to be responsible for an increase in the number of binding sites at low ionic strength and also for the appearance of the second wave on the melting curves of the single-stranded RNA-proflavine complexes at high ionic strength."}
{"id": "PMID:206826", "title": "[Comparison between combination therapy with clofibrate and beta-pyridylcarbinol and clofibrate monotherapy (author's transl].", "content": "In order to determine whether the lipid-lowering effect of combined treatment with clofibrate and beta-Pyridylcarbinol exceeds that of clofibrate monotherapy, a double-blind crossover study was performed. 17 patients with primary hyperlipoproteinemia of Type IIa and 10 patients with primary hyperlipoproteinemia of Type IIb received either Lipofacton (1.000 mg clofibrate and 50 mg beta-pyridylcarbinol per day) or clofibrate (1.500 mg per day) for a period of 6 weeks each. Before beginning therapy and between both periods of medication, placebo was administered for 14 days. In both total plasma and in the LDL fraction the cholesterol level was lowered by less than 10% for both substances. In patients with hyperlipoproteinemia of Type IIb, the triglyceride levels were lowered by about 40%.", "contents": "[Comparison between combination therapy with clofibrate and beta-pyridylcarbinol and clofibrate monotherapy (author's transl]. In order to determine whether the lipid-lowering effect of combined treatment with clofibrate and beta-Pyridylcarbinol exceeds that of clofibrate monotherapy, a double-blind crossover study was performed. 17 patients with primary hyperlipoproteinemia of Type IIa and 10 patients with primary hyperlipoproteinemia of Type IIb received either Lipofacton (1.000 mg clofibrate and 50 mg beta-pyridylcarbinol per day) or clofibrate (1.500 mg per day) for a period of 6 weeks each. Before beginning therapy and between both periods of medication, placebo was administered for 14 days. In both total plasma and in the LDL fraction the cholesterol level was lowered by less than 10% for both substances. In patients with hyperlipoproteinemia of Type IIb, the triglyceride levels were lowered by about 40%."}
{"id": "PMID:206827", "title": "[Distribution of cytomegalovirus in children and adults in the Munich area (author's transl)].", "content": "In a regional contamination study 798 healthy persons from the Munich area were examined for cytomegalovirus antibodies. The highest proportion of antibodies (60%) was found in neonates in the first days of life. At the age of 6 to 24 months, only 10% of the children were still seropositive. At this time the maternal antibodies were no longer important. In late adult life, 57% of those examined possessed antibodies against the virus. An attempt was also made to isolate the cytomegalovirus from the urine of 157 healthy persons. This isolation was only possible in three apparently healthy infants aged from 3 to 12 months.", "contents": "[Distribution of cytomegalovirus in children and adults in the Munich area (author's transl)]. In a regional contamination study 798 healthy persons from the Munich area were examined for cytomegalovirus antibodies. The highest proportion of antibodies (60%) was found in neonates in the first days of life. At the age of 6 to 24 months, only 10% of the children were still seropositive. At this time the maternal antibodies were no longer important. In late adult life, 57% of those examined possessed antibodies against the virus. An attempt was also made to isolate the cytomegalovirus from the urine of 157 healthy persons. This isolation was only possible in three apparently healthy infants aged from 3 to 12 months."}
{"id": "PMID:206828", "title": "Unscheduled DNA synthesis induced in mouse spermatids after combined treatment with methyl methanesulfonate and X-rays.", "content": "Unscheduled DNA synthesis (UDS), which is considered to be DNA repair, has been studied in early- to mid-spermatid stages of the mouse after combined treatments with X-rays and methyl methanesulfonate (MMS). UDS in spermatids was detected by giving testicular injections of [methyl-3H]thymidine ([3H]dThd) and making use of the fact that no scheduled DNA synthesis occurs in the germ cells after the last S period in primary spermatocytes. X-rays and MMS are each able to induce UDS in mouse spermatids. However, there was a statistically significant reduction in the amount of UDS observed when X-ray exposures of from 200 to 600 R were given 4 h before an i.p. injection of 75 mg/kg of MMS and concurrent testicular injections of [3H]dThd. This reduction in UDS is more than can be explained by the completion of repair of X-ray-induced DNA lesions. We suggest that the reduction in UDS is the result of an X-ray-produced impairment of a least a part of the repair mechanism involved in correcting MMS-induced DNA lesions. When the time interval between a 600-R X-ray exposure and MMS treatment was between 3 and 20 h (latest time interval s;udied) there was a statistically significant reduction of UDS in the spermatids. No significant decrease in UDS response occurred when the time interval between radiation exposure and MMS treatment was less than approximately 3 h.", "contents": "Unscheduled DNA synthesis induced in mouse spermatids after combined treatment with methyl methanesulfonate and X-rays. Unscheduled DNA synthesis (UDS), which is considered to be DNA repair, has been studied in early- to mid-spermatid stages of the mouse after combined treatments with X-rays and methyl methanesulfonate (MMS). UDS in spermatids was detected by giving testicular injections of [methyl-3H]thymidine ([3H]dThd) and making use of the fact that no scheduled DNA synthesis occurs in the germ cells after the last S period in primary spermatocytes. X-rays and MMS are each able to induce UDS in mouse spermatids. However, there was a statistically significant reduction in the amount of UDS observed when X-ray exposures of from 200 to 600 R were given 4 h before an i.p. injection of 75 mg/kg of MMS and concurrent testicular injections of [3H]dThd. This reduction in UDS is more than can be explained by the completion of repair of X-ray-induced DNA lesions. We suggest that the reduction in UDS is the result of an X-ray-produced impairment of a least a part of the repair mechanism involved in correcting MMS-induced DNA lesions. When the time interval between a 600-R X-ray exposure and MMS treatment was between 3 and 20 h (latest time interval s;udied) there was a statistically significant reduction of UDS in the spermatids. No significant decrease in UDS response occurred when the time interval between radiation exposure and MMS treatment was less than approximately 3 h."}
{"id": "PMID:206835", "title": "Hyperbaric oxygen and radiation therapy in the management of glioblastoma.", "content": "A pilot clinical trial on radiotherapy of glioblastoma with and without hyperbaric oxygen was performed at the Columbia-Presbyterian Medical Center. Eighty previously untreated patients with histologically proved glioblastoma were evaluated; 38 were irradiated under hyperbaric oxygen and 42 (controls) in atmospheric air. The survival rates were calculated according to the actuarial analysis method. At the end of 18 months, the survival rate appeared considerably higher in the oxygen group (28%) than in the controls (10%). At the end of 36 months, no patients in the control group survived, whereas 2 patients in the oxygen group were alive beyond 45 and 48 months, respectively. The median survival time was 38 weeks for those treated under oxygen and 31 weeks for the air control group. Owing to the small population samples and the pilot nature of this study, the difference in survival rates between the two groups was not statistically significant. The toxicity of hyperbaric oxygen was well tolerated by most patients, and the quality of survival in the hyperbaric oxygen group was equal to or slightly better than that of the control group. This pilot clinical study paved the way for further controlled clinical trials of hyperbaric oxygen and oxygen-mimicking drugs, including the electron-affinic compounds that could have differentially sensitized the hypoxic tumor cells.", "contents": "Hyperbaric oxygen and radiation therapy in the management of glioblastoma. A pilot clinical trial on radiotherapy of glioblastoma with and without hyperbaric oxygen was performed at the Columbia-Presbyterian Medical Center. Eighty previously untreated patients with histologically proved glioblastoma were evaluated; 38 were irradiated under hyperbaric oxygen and 42 (controls) in atmospheric air. The survival rates were calculated according to the actuarial analysis method. At the end of 18 months, the survival rate appeared considerably higher in the oxygen group (28%) than in the controls (10%). At the end of 36 months, no patients in the control group survived, whereas 2 patients in the oxygen group were alive beyond 45 and 48 months, respectively. The median survival time was 38 weeks for those treated under oxygen and 31 weeks for the air control group. Owing to the small population samples and the pilot nature of this study, the difference in survival rates between the two groups was not statistically significant. The toxicity of hyperbaric oxygen was well tolerated by most patients, and the quality of survival in the hyperbaric oxygen group was equal to or slightly better than that of the control group. This pilot clinical study paved the way for further controlled clinical trials of hyperbaric oxygen and oxygen-mimicking drugs, including the electron-affinic compounds that could have differentially sensitized the hypoxic tumor cells."}
{"id": "PMID:206836", "title": "Treatment of an intracerebral rat brain tumor with Corynebacterium parvum and radiation.", "content": "Rats bearing intracranial brain tumors were treated with single ip injections of the killed Corynebacterium parvum, a single dose of X-rays, or a combination of both treatments. Animals given injections of 2.6 mg C. parvum 12 days after implantation of the tumor had a median survival time (MST) of 50 days compared with an MST of 44 days for an untreated group. These animals given C. parvum had a 33% increased life-span (ILS) that was significant at the P=0.05 level. Although the MST of animals that received C. parvum 2 days before a tumor X-ray dose of 3,015 rads on day 14 was greater than that of rats given irradiation alone, the ILS of the group administered both treatments was not significant relative to the latter group. The MST of animals that received C. parvum 7 days before irradiation was not different from that of animals given injections of C. parvum 1 day postirradiation.", "contents": "Treatment of an intracerebral rat brain tumor with Corynebacterium parvum and radiation. Rats bearing intracranial brain tumors were treated with single ip injections of the killed Corynebacterium parvum, a single dose of X-rays, or a combination of both treatments. Animals given injections of 2.6 mg C. parvum 12 days after implantation of the tumor had a median survival time (MST) of 50 days compared with an MST of 44 days for an untreated group. These animals given C. parvum had a 33% increased life-span (ILS) that was significant at the P=0.05 level. Although the MST of animals that received C. parvum 2 days before a tumor X-ray dose of 3,015 rads on day 14 was greater than that of rats given irradiation alone, the ILS of the group administered both treatments was not significant relative to the latter group. The MST of animals that received C. parvum 7 days before irradiation was not different from that of animals given injections of C. parvum 1 day postirradiation."}
{"id": "PMID:206837", "title": "Chemical- and virus-induced brain tumors.", "content": "Experimental animal models resembling most human brain tumor types can be induced by exposure to oncogenic viruses or chemical carcinogens: Astrocytomas and glioblastoma multiforme can be produced experimentally by intracerebral injection of oncornaviruses, whereas medulloblastomas, choroid plexus papillomas, and ependymomas can be induced by the papovaviruses. Adenoviruses have been utilized to cause medulloepitheliomas, neuroblastomas, and retinoblastomas. All three groups of viruses can result in sarcoma production. Gliomas represent the primary tumor type induced in the brain by chemical carcinogens. These autochthonous tumor systems are reviewed, with emphasis on methods, tumor type, latency period, advantages, and disadvantages. In addition, recent investigations of molecular events involved in neoplastic transformation by chemical carcinogens are summarized.", "contents": "Chemical- and virus-induced brain tumors. Experimental animal models resembling most human brain tumor types can be induced by exposure to oncogenic viruses or chemical carcinogens: Astrocytomas and glioblastoma multiforme can be produced experimentally by intracerebral injection of oncornaviruses, whereas medulloblastomas, choroid plexus papillomas, and ependymomas can be induced by the papovaviruses. Adenoviruses have been utilized to cause medulloepitheliomas, neuroblastomas, and retinoblastomas. All three groups of viruses can result in sarcoma production. Gliomas represent the primary tumor type induced in the brain by chemical carcinogens. These autochthonous tumor systems are reviewed, with emphasis on methods, tumor type, latency period, advantages, and disadvantages. In addition, recent investigations of molecular events involved in neoplastic transformation by chemical carcinogens are summarized."}
{"id": "PMID:206838", "title": "Nomenclature for gliomas.", "content": "Gliomas, derived from astrocytes, oligodendroglia, or ependyma, are each united into a continuum by a graduation of anaplasia. Neoplasms originate at all levels of each continuum; subsequently, some move along its declivity. Conversely, neuroblastic tumors may differentiate, whereas concomitantly in the same lesion, the glial stroma may dedifferentiate. Anaplastic glia, as in a glioblastoma multiforme, can initiate malignant transformation in alien cells.", "contents": "Nomenclature for gliomas. Gliomas, derived from astrocytes, oligodendroglia, or ependyma, are each united into a continuum by a graduation of anaplasia. Neoplasms originate at all levels of each continuum; subsequently, some move along its declivity. Conversely, neuroblastic tumors may differentiate, whereas concomitantly in the same lesion, the glial stroma may dedifferentiate. Anaplastic glia, as in a glioblastoma multiforme, can initiate malignant transformation in alien cells."}
{"id": "PMID:206839", "title": "Pathologic tumor type and response to treatment.", "content": "The general biology of the common primary brain tumors is reviewed, as are the results of surgery, radiation therapy, and chemotherapy for these neoplasms. The problems of classification, particularly of the astrocytomas, are noted, with the resultant difficulties in comparing different series. The development and consistent application of a widely acceptable nomenclature for brain tumors would be useful in the comparison of various therapies and for ease in communication. Further, a better general understanding of the biology of the various brain tumors is desirable. Reliable data relative to old or new forms of therapy seem to require national or regional studies in view of the relative rarity of some of these tumors. Except for medulloblastoma, the best results of therapy thus far are only slightly encouraging. We must also be aware that some of our treatments may do as much harm to some patients as their tumors; therefore, we must all strive for a high autopsy rate so that we can monitor our therapy and recognize unexpected complications as quickly as possible.", "contents": "Pathologic tumor type and response to treatment. The general biology of the common primary brain tumors is reviewed, as are the results of surgery, radiation therapy, and chemotherapy for these neoplasms. The problems of classification, particularly of the astrocytomas, are noted, with the resultant difficulties in comparing different series. The development and consistent application of a widely acceptable nomenclature for brain tumors would be useful in the comparison of various therapies and for ease in communication. Further, a better general understanding of the biology of the various brain tumors is desirable. Reliable data relative to old or new forms of therapy seem to require national or regional studies in view of the relative rarity of some of these tumors. Except for medulloblastoma, the best results of therapy thus far are only slightly encouraging. We must also be aware that some of our treatments may do as much harm to some patients as their tumors; therefore, we must all strive for a high autopsy rate so that we can monitor our therapy and recognize unexpected complications as quickly as possible."}
{"id": "PMID:206840", "title": "Selected observations on the epidemiology of pharyngeal cancers.", "content": "The epidemiology of nasopharyngeal cancer (NPC) has been compared with that of other pharyngeal cancers in Los Angeles County. Epstein-Barr virus (EBV) antibody titers were elevated in Caucasians with pharyngeal squamous cell carcinomas regardless of subsite. As expected, an excess of NPC cases was found among Chinese. The role of various etiologic factors in NPC including EBV, inhaled carcinogens, and salted fish was discussed.", "contents": "Selected observations on the epidemiology of pharyngeal cancers. The epidemiology of nasopharyngeal cancer (NPC) has been compared with that of other pharyngeal cancers in Los Angeles County. Epstein-Barr virus (EBV) antibody titers were elevated in Caucasians with pharyngeal squamous cell carcinomas regardless of subsite. As expected, an excess of NPC cases was found among Chinese. The role of various etiologic factors in NPC including EBV, inhaled carcinogens, and salted fish was discussed."}
{"id": "PMID:206842", "title": "Indirect complement fixation test with foot-and-mouth disease virus antigen concentrated by polyethylene glycol precipitation.", "content": "To a BHK-21 cell culture fluid infected with the O, A, or Asia 1 type of foot-and-mouth disease (FMD) virus was added polyethylene glycol 16000 to a concentration of 10% (w/v). Then the fluid was concentrated to one-tenth of the original volume. The resulting concentrated virus antigens showed a complement fixation (CF) titer ranging from 12 to 14. The rate of recovery of CF activity was in a range of 40 approximately 80%. Each antigen was applied to the indirect complement fixation (ICF) test with serum from cattle infected experimentally with the respective type of virus to estimate antibody titers. When antibody was examined for a rise and fall, it began to be detected 4 approximately 7 days after inoculation and was detectable even 63 days after inoculation. It showed a tendency to exhibit a rise and fall parallel with that of neutralizing antibody, although it was always lower in titer than this antibody. ICF antibody corresponding to one type of virus was type-specific, presenting little crossing with a heterologous antigen. As a result, it was clarified that such antigen as prepared from an infected cell culture fluid after concentration with polyethylene glycol was applicable to the ICF test for the estimation of the titer of antibody against FMD virus.", "contents": "Indirect complement fixation test with foot-and-mouth disease virus antigen concentrated by polyethylene glycol precipitation. To a BHK-21 cell culture fluid infected with the O, A, or Asia 1 type of foot-and-mouth disease (FMD) virus was added polyethylene glycol 16000 to a concentration of 10% (w/v). Then the fluid was concentrated to one-tenth of the original volume. The resulting concentrated virus antigens showed a complement fixation (CF) titer ranging from 12 to 14. The rate of recovery of CF activity was in a range of 40 approximately 80%. Each antigen was applied to the indirect complement fixation (ICF) test with serum from cattle infected experimentally with the respective type of virus to estimate antibody titers. When antibody was examined for a rise and fall, it began to be detected 4 approximately 7 days after inoculation and was detectable even 63 days after inoculation. It showed a tendency to exhibit a rise and fall parallel with that of neutralizing antibody, although it was always lower in titer than this antibody. ICF antibody corresponding to one type of virus was type-specific, presenting little crossing with a heterologous antigen. As a result, it was clarified that such antigen as prepared from an infected cell culture fluid after concentration with polyethylene glycol was applicable to the ICF test for the estimation of the titer of antibody against FMD virus."}
{"id": "PMID:206843", "title": "Interactions of opiates and prostaglandins E with regard to cyclic AMP in striatal tissue of rats in vitro.", "content": "The effects of prostaglandins E on the concentration of cyclic AMP (cAMP) and a possible antagonism of opiates vs. prostaglandins E were studied in homogenates and in slices of rat striata in vitro. In homogenates, PGE1 or PGE2 did not affect the synthesis of cAMP. Morphine slightly lowered the cAMP synthesis, in presence or absence of PGE1 or PGE2. In slices, PGE2 significantly elevated the cAMP concentrations, either in presence or in absence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Morphine, met-enkephalin and levorphanol, but not dextrorphan, antagonized this rise of cAMP. The effect of morphine was antagonized by naloxone. Adenosine or an elevation of K+-ions raised the cAMP concentrations, and PGE2 induced a further increase. In presence of elevated K+-ions or adenosine, however, morphine did not antagonize the PGE2-induced rise of cAMP concentration. It is suggested that under some experimental conditions described in the literature, endogenous activators of cAMP formation, e.g. adenosine, might mask the inhibitory effect of opiates on stimulation of opiates on stimulation of cAMP synthesis induced by prostaglandins E.", "contents": "Interactions of opiates and prostaglandins E with regard to cyclic AMP in striatal tissue of rats in vitro. The effects of prostaglandins E on the concentration of cyclic AMP (cAMP) and a possible antagonism of opiates vs. prostaglandins E were studied in homogenates and in slices of rat striata in vitro. In homogenates, PGE1 or PGE2 did not affect the synthesis of cAMP. Morphine slightly lowered the cAMP synthesis, in presence or absence of PGE1 or PGE2. In slices, PGE2 significantly elevated the cAMP concentrations, either in presence or in absence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Morphine, met-enkephalin and levorphanol, but not dextrorphan, antagonized this rise of cAMP. The effect of morphine was antagonized by naloxone. Adenosine or an elevation of K+-ions raised the cAMP concentrations, and PGE2 induced a further increase. In presence of elevated K+-ions or adenosine, however, morphine did not antagonize the PGE2-induced rise of cAMP concentration. It is suggested that under some experimental conditions described in the literature, endogenous activators of cAMP formation, e.g. adenosine, might mask the inhibitory effect of opiates on stimulation of opiates on stimulation of cAMP synthesis induced by prostaglandins E."}
{"id": "PMID:206844", "title": "ACTH-induced lipolysis in rat adipocytes: structure-activity relationships.", "content": "The lipolytic action of natural porcine ACTH1(-39) and of a number of highly purified synthetic ACTH peptide fragments was studied using rat adipocytes. Of the analogues tested, only ACTH1(-24) exhibited full lipolytic activity with respect to intrinsic activity and affinity. Several shorter fragments appeared to be full agonists but had lower affinity. Fragments ACTH5(-10) and ACTH7(-10) were inactive. No antagonistic effects against the lipolytic action of ACTH could be demonstrated with substimulatory doses of ACTH1(-16), ACTH1(-10), ACTH7(-24) and ACTH11(-24). Based on the relative potency derived from dose-response curves, a more refined model with respect to the active centers being encoded in various sequences of the hormone, is proposed.", "contents": "ACTH-induced lipolysis in rat adipocytes: structure-activity relationships. The lipolytic action of natural porcine ACTH1(-39) and of a number of highly purified synthetic ACTH peptide fragments was studied using rat adipocytes. Of the analogues tested, only ACTH1(-24) exhibited full lipolytic activity with respect to intrinsic activity and affinity. Several shorter fragments appeared to be full agonists but had lower affinity. Fragments ACTH5(-10) and ACTH7(-10) were inactive. No antagonistic effects against the lipolytic action of ACTH could be demonstrated with substimulatory doses of ACTH1(-16), ACTH1(-10), ACTH7(-24) and ACTH11(-24). Based on the relative potency derived from dose-response curves, a more refined model with respect to the active centers being encoded in various sequences of the hormone, is proposed."}
{"id": "PMID:206849", "title": "In vitro regulation of ACTH release from neurointermediate lobe of rat hypophysis. I. Effect of crude hypothalamic extracts.", "content": "Using incubated glands, we showed that cerebral cortex and liver extracts (CCE and LE) stimulated ACTH release from neurointermediate lobe (NIL) of hypophysis as well as hypothalmus extract (HE) did. Moreover, the HE-induced ACTH release was much smaller for the NIL (1.9 X basal level) than for the anterior lobe (AL; 13.7 x basal level). Thus, under these conditions, HE seemed to have no specific effect on NIL ACTH release. Using superfused glands, we showed: (a) that both spontaneous and HE-induced ACTH release decreased during superfusion; (b) that using this system, a specific stimulatory effect on HE on NIL was observed. In contrast to HE, CCE and LE had only a small effect on NIL ACTH release (always less than 20% of that caused by HE) which could be considered as a nonspecific response; (c) that trypsin suppressed the stimulating effect on HE as well on NIL as on AL; and (d) that arginine antidiuretic hormone (ADH) was not responsible for the stimulating effect of HE on NIL ACTH release, because synthetic ADH had no effect and HE containing ADH (from normal rats) or HE containing no ADH (from Brattleboro rats or from immunoneutralization of ADH in normal HE) had the same effect. From these results, we can conclude that HE contain a peptidic factor different from ADH which is able to stimulate in vitro release of ACTH from the NIL.", "contents": "In vitro regulation of ACTH release from neurointermediate lobe of rat hypophysis. I. Effect of crude hypothalamic extracts. Using incubated glands, we showed that cerebral cortex and liver extracts (CCE and LE) stimulated ACTH release from neurointermediate lobe (NIL) of hypophysis as well as hypothalmus extract (HE) did. Moreover, the HE-induced ACTH release was much smaller for the NIL (1.9 X basal level) than for the anterior lobe (AL; 13.7 x basal level). Thus, under these conditions, HE seemed to have no specific effect on NIL ACTH release. Using superfused glands, we showed: (a) that both spontaneous and HE-induced ACTH release decreased during superfusion; (b) that using this system, a specific stimulatory effect on HE on NIL was observed. In contrast to HE, CCE and LE had only a small effect on NIL ACTH release (always less than 20% of that caused by HE) which could be considered as a nonspecific response; (c) that trypsin suppressed the stimulating effect on HE as well on NIL as on AL; and (d) that arginine antidiuretic hormone (ADH) was not responsible for the stimulating effect of HE on NIL ACTH release, because synthetic ADH had no effect and HE containing ADH (from normal rats) or HE containing no ADH (from Brattleboro rats or from immunoneutralization of ADH in normal HE) had the same effect. From these results, we can conclude that HE contain a peptidic factor different from ADH which is able to stimulate in vitro release of ACTH from the NIL."}
{"id": "PMID:206850", "title": "Effect of spinal cord transection on the endocrine and blood pressure responses to intravenous clonidine.", "content": "To determine whether the inhibitory effect of clonidine (CLON) on renin secretion is due in part to a direct action on the kidneys or due entirely to an action on the brain, the drug was administered intravenously in a dose of 30 microgram/kg to dogs in which the spinal cord had been transected in the cervical region. Renal perfusion pressure was held constant by adjusting a suprarenal aortic clamp. The decrease in plasma renin activity produced by CLON in dogs with intact spinal cords was abolished, and in 5 of 8 dogs tested, plasma renin activity rose. The decrease in blood pressure seen in control dogs was replaced by a prolonged pressor response. The ACTH response, as measured by plasma corticoids, and the growth hormone (GH) response were not significantly reduced. The data indicate that at least at this dose, the depressor response and the decrease in renin secretion produced by CLON are completely central in origin.", "contents": "Effect of spinal cord transection on the endocrine and blood pressure responses to intravenous clonidine. To determine whether the inhibitory effect of clonidine (CLON) on renin secretion is due in part to a direct action on the kidneys or due entirely to an action on the brain, the drug was administered intravenously in a dose of 30 microgram/kg to dogs in which the spinal cord had been transected in the cervical region. Renal perfusion pressure was held constant by adjusting a suprarenal aortic clamp. The decrease in plasma renin activity produced by CLON in dogs with intact spinal cords was abolished, and in 5 of 8 dogs tested, plasma renin activity rose. The decrease in blood pressure seen in control dogs was replaced by a prolonged pressor response. The ACTH response, as measured by plasma corticoids, and the growth hormone (GH) response were not significantly reduced. The data indicate that at least at this dose, the depressor response and the decrease in renin secretion produced by CLON are completely central in origin."}
{"id": "PMID:206851", "title": "An improved radioimmunoassay for alpha-melanocyte-stimulating hormone (alpha-MSH) in the rat: serum and pituitary alpha-MSH levels after drugs which modify catecholaminergic neurotransmission.", "content": "A modification of our previous radioimmunoassay (RIA) for alpha-melanocyte-stimulating hormone (alpha-MSH) is described that permits the measurement of circulating levels in the rat without the need for an extraction procedure. Using this method, serum and neurointermediate lobe (NIL) immunoreactive alpha-MSH levels were measured in rats after administration of haloperidol, 2-bromo alpha-ergocryptine (CB 154), and alpha-methyl-p-tyrosine (alpha-MPT). Haloperidol caused a rapid increase, alpha-MPT a slow increase, and CB 154 a rapid decrease in serum alpha-MSH. At the time intervals studied none of the drugs had any significant effect on NIL alpha-MSH content. It was concluded from the results of the above drug treatments that modulation of dopaminergic neurotransmission both pre- and postsynaptically produces changes in serum immunoreactive alpha-MSH levels. This supports the suggestion that circulating alpha-MSH in the rat is under an inhibitory control by a catecholaminergic system.", "contents": "An improved radioimmunoassay for alpha-melanocyte-stimulating hormone (alpha-MSH) in the rat: serum and pituitary alpha-MSH levels after drugs which modify catecholaminergic neurotransmission. A modification of our previous radioimmunoassay (RIA) for alpha-melanocyte-stimulating hormone (alpha-MSH) is described that permits the measurement of circulating levels in the rat without the need for an extraction procedure. Using this method, serum and neurointermediate lobe (NIL) immunoreactive alpha-MSH levels were measured in rats after administration of haloperidol, 2-bromo alpha-ergocryptine (CB 154), and alpha-methyl-p-tyrosine (alpha-MPT). Haloperidol caused a rapid increase, alpha-MPT a slow increase, and CB 154 a rapid decrease in serum alpha-MSH. At the time intervals studied none of the drugs had any significant effect on NIL alpha-MSH content. It was concluded from the results of the above drug treatments that modulation of dopaminergic neurotransmission both pre- and postsynaptically produces changes in serum immunoreactive alpha-MSH levels. This supports the suggestion that circulating alpha-MSH in the rat is under an inhibitory control by a catecholaminergic system."}
{"id": "PMID:206852", "title": "Inhibition of corticotropin secretion by hypothalamic administration of indomethacin.", "content": "The importance of endogenous prostaglandins (PGs) in regulating CRF release was investigated by administering the PG synthesis inhibitor, indomethacin (Ind), in specific hypothalamic regions to adult female rats. Solid Ind pellets placed in the anterior hypothalamic area (AHA) significantly reduced the elevated levels of plasma corticosterone normally observed after the surgical stress of the stereotaxic procedure. Similar pellets placed in the hypothalamic median eminence region (ME) completely blocked the normal compensatory hypertrophy observed 48 h after unilateral adrenalectomy. Plasma corticosterone secretion in response to hemorrhage (1% b.w.) or laparotomy with intestinal manipulation (LAP) in dexamethasone pretreated rats was reduced by Ind pellets, or Ind in phosphate buffer (BUF), respectively, implanted 2 h prior to the stress. These data suggest that the PGs may be important in mediating CRF release in response to a variety of stimuli.", "contents": "Inhibition of corticotropin secretion by hypothalamic administration of indomethacin. The importance of endogenous prostaglandins (PGs) in regulating CRF release was investigated by administering the PG synthesis inhibitor, indomethacin (Ind), in specific hypothalamic regions to adult female rats. Solid Ind pellets placed in the anterior hypothalamic area (AHA) significantly reduced the elevated levels of plasma corticosterone normally observed after the surgical stress of the stereotaxic procedure. Similar pellets placed in the hypothalamic median eminence region (ME) completely blocked the normal compensatory hypertrophy observed 48 h after unilateral adrenalectomy. Plasma corticosterone secretion in response to hemorrhage (1% b.w.) or laparotomy with intestinal manipulation (LAP) in dexamethasone pretreated rats was reduced by Ind pellets, or Ind in phosphate buffer (BUF), respectively, implanted 2 h prior to the stress. These data suggest that the PGs may be important in mediating CRF release in response to a variety of stimuli."}
{"id": "PMID:206853", "title": "Effects of hypothalamic lesions and drugs interfering with dopaminergic transmission on pituitary MSH content of rats.", "content": "The physiological significance of the dopaminergic innervation of the pars intermedia was studied in rats. Electrothermic lesions were made in the mediobasal hypothalamus in order to destroy all hypothalamo-hypophysial connections. Pituitary MSH content decreased to 25% of control values 8 h after lesioning. From the 1st day, however, pituitary MSH content gradually increased, reaching control levels after about 1 week. Haloperidol and pimozide (both neuroleptics) were used to block specifically dopamine (DA)-receptors. Single administration of these drugs induced a time and dose dependent reduction in pituitary MSH. A maximal decrease to about 60% was found 4-5 h after i.p. administration of 2.5 mg/kg haloperidol and 1.0 mg/kg pimozide. Apomorphine and 2-Br-alpha-ergocryptine (DA-receptor stimulating drugs), had no effect on pituitary MSH stores of intact rats, but completely prevented the lesion-induced fall in pituitary MSH content. The results show that DA-receptors located within the pituitary itself are involved in the control of MSH release indicating that the effect of hypothalamic lesions on pituitary MSH content is primarily caused by interruption of dopaminergic neurotransmission in the hypophysis. We conclude therefore that the dopaminergic arcuato-hypophysial neurones innervating the pars intermedia tonically inhibit the release of MSH in intact rats.", "contents": "Effects of hypothalamic lesions and drugs interfering with dopaminergic transmission on pituitary MSH content of rats. The physiological significance of the dopaminergic innervation of the pars intermedia was studied in rats. Electrothermic lesions were made in the mediobasal hypothalamus in order to destroy all hypothalamo-hypophysial connections. Pituitary MSH content decreased to 25% of control values 8 h after lesioning. From the 1st day, however, pituitary MSH content gradually increased, reaching control levels after about 1 week. Haloperidol and pimozide (both neuroleptics) were used to block specifically dopamine (DA)-receptors. Single administration of these drugs induced a time and dose dependent reduction in pituitary MSH. A maximal decrease to about 60% was found 4-5 h after i.p. administration of 2.5 mg/kg haloperidol and 1.0 mg/kg pimozide. Apomorphine and 2-Br-alpha-ergocryptine (DA-receptor stimulating drugs), had no effect on pituitary MSH stores of intact rats, but completely prevented the lesion-induced fall in pituitary MSH content. The results show that DA-receptors located within the pituitary itself are involved in the control of MSH release indicating that the effect of hypothalamic lesions on pituitary MSH content is primarily caused by interruption of dopaminergic neurotransmission in the hypophysis. We conclude therefore that the dopaminergic arcuato-hypophysial neurones innervating the pars intermedia tonically inhibit the release of MSH in intact rats."}
{"id": "PMID:206859", "title": "Reduced neuromuscular transmission safety factor in multiple sclerosis.", "content": "Regional intravascular injections of d-tubocurarine (0.3 mg) were administered in the hands of 23 normal subjects and 19 patients with multiple sclerosis. The degree of neuromuscular block and rate of recovery were determined by measuring the amplitude of the first dorsal interosseus muscle action potential which was evoked periodically by trains of five stimuli (3 Hz each) to the ulnar nerve. In normal subjects, the first response to the train returned to its preinjection level after 20.0 +/- 8.5 minutes and the fifth response after 27.6 +/- 7.8 minutes. Multiple sclerosis patients showed a significantly delayed recovery of the first response (58 percent of patients) and of the fifth response (42 percent), suggesting a latent defect of neuromuscular transmission.", "contents": "Reduced neuromuscular transmission safety factor in multiple sclerosis. Regional intravascular injections of d-tubocurarine (0.3 mg) were administered in the hands of 23 normal subjects and 19 patients with multiple sclerosis. The degree of neuromuscular block and rate of recovery were determined by measuring the amplitude of the first dorsal interosseus muscle action potential which was evoked periodically by trains of five stimuli (3 Hz each) to the ulnar nerve. In normal subjects, the first response to the train returned to its preinjection level after 20.0 +/- 8.5 minutes and the fifth response after 27.6 +/- 7.8 minutes. Multiple sclerosis patients showed a significantly delayed recovery of the first response (58 percent of patients) and of the fifth response (42 percent), suggesting a latent defect of neuromuscular transmission."}
{"id": "PMID:206860", "title": "Multiple sclerosis: cellular and humoral immune responses to several viruses.", "content": "One hundred and eight multiple sclerosis (MS) patients and 108 matched controls were studied for antibody levels and cellular immune responses to several viruses. There were significant increases in the mean titers of complement fixation (CF) or hemagglutination inhibition (HI), and complement-mediated cytotoxicity (CMC) tests for measles antibodies in MS patients; there was no increase in antibody titers to herpesviruses 1 and 2, or cytomegalovirus (CMV). The direct migration inhibition (DMI) tests showed no difference between MS patients and controls for measles, CMV, herpesviruses 1 and 2, or vaccinia virus antigens. Lymphocyte-mediated cytotoxicity (LMC) tests showed no difference between patients and controls, using cultures infected with measles and CMV viruses. In a study of stimulation or blocking of the LMC response by serum or cerebrospinal fluid (CSF), no effect was found. Therefore, increased levels of measles antibody in serum were again  demonstrated in  MS patients, but  there  was  no  difference  in  these  patients' cellular immunity to measles virus versus that of the controls, and there was no abnormality of cellular immunity against the other viruses tested.", "contents": "Multiple sclerosis: cellular and humoral immune responses to several viruses. One hundred and eight multiple sclerosis (MS) patients and 108 matched controls were studied for antibody levels and cellular immune responses to several viruses. There were significant increases in the mean titers of complement fixation (CF) or hemagglutination inhibition (HI), and complement-mediated cytotoxicity (CMC) tests for measles antibodies in MS patients; there was no increase in antibody titers to herpesviruses 1 and 2, or cytomegalovirus (CMV). The direct migration inhibition (DMI) tests showed no difference between MS patients and controls for measles, CMV, herpesviruses 1 and 2, or vaccinia virus antigens. Lymphocyte-mediated cytotoxicity (LMC) tests showed no difference between patients and controls, using cultures infected with measles and CMV viruses. In a study of stimulation or blocking of the LMC response by serum or cerebrospinal fluid (CSF), no effect was found. Therefore, increased levels of measles antibody in serum were again  demonstrated in  MS patients, but  there  was  no  difference  in  these  patients' cellular immunity to measles virus versus that of the controls, and there was no abnormality of cellular immunity against the other viruses tested."}
{"id": "PMID:206861", "title": "The immunological response to intact and dissociated blue-tongue virus in mice.", "content": "Antigenic fractions of bluetongue virus were separated by ultracentrifugation in Tris-buffered CsCl gradients at pH 6, 7 or 8 and the bluetongue virus polypeptide composition of the bands isolated from these gradeints was monitored by polyacrylamide gel slab electrophoresis. The immunological response to these fractions in mice was determined by a haemolytic plaque-forming cell assay, using sheep erythrocytes onto which intact bluetongue virus was adsorbed as lytic indicator cells. Isolated outer layer bluetongue virus polypeptide 2, from gradients at pH 6, and polypeptides 2 and 5, from gradients at pH 7, produced a strong primary IgM plaque-forming cell response. The subviral particles of density 1, 39 g.cm-3 and the bluetongue virus core particles of density 1,42 g.cm-3 also stimulated an IgM response at least as strong as that to intact bluetongue virus of density 1,38 g.cm-3. The isolated bluetongue virus fractions therefore appear to maintain their immunogenic integrity as effectively as those of intact bluetongue virus. The pattern of the immune response to bluetongue virus type 4 is similar to that of type 10.", "contents": "The immunological response to intact and dissociated blue-tongue virus in mice. Antigenic fractions of bluetongue virus were separated by ultracentrifugation in Tris-buffered CsCl gradients at pH 6, 7 or 8 and the bluetongue virus polypeptide composition of the bands isolated from these gradeints was monitored by polyacrylamide gel slab electrophoresis. The immunological response to these fractions in mice was determined by a haemolytic plaque-forming cell assay, using sheep erythrocytes onto which intact bluetongue virus was adsorbed as lytic indicator cells. Isolated outer layer bluetongue virus polypeptide 2, from gradients at pH 6, and polypeptides 2 and 5, from gradients at pH 7, produced a strong primary IgM plaque-forming cell response. The subviral particles of density 1, 39 g.cm-3 and the bluetongue virus core particles of density 1,42 g.cm-3 also stimulated an IgM response at least as strong as that to intact bluetongue virus of density 1,38 g.cm-3. The isolated bluetongue virus fractions therefore appear to maintain their immunogenic integrity as effectively as those of intact bluetongue virus. The pattern of the immune response to bluetongue virus type 4 is similar to that of type 10."}
{"id": "PMID:206862", "title": "Diarrhoea in pigs induced by rotavirus.", "content": "Electron microscope examination of the faeces of scouring pigs revealed virus particles which were morphologically indistinguishable from rotavirus (reo-like), a virus associated with diarrhoea in neonatal pigs (Lecce, King & Mock, 1976). This is the first record of the virus in the Republic of South Africa.", "contents": "Diarrhoea in pigs induced by rotavirus. Electron microscope examination of the faeces of scouring pigs revealed virus particles which were morphologically indistinguishable from rotavirus (reo-like), a virus associated with diarrhoea in neonatal pigs (Lecce, King & Mock, 1976). This is the first record of the virus in the Republic of South Africa."}
{"id": "PMID:206863", "title": "Preoperative facial paralysis in malignant parotid tumours.", "content": "Preoperative paralysis of the facial nerve was found in 145 of 1,029 patients with malignant parotid tumours (14%) treated at nine university clinics in Scandinavia. The incidence of facial paralysis varied between the different clinics. A parellelism between the incidence of the facial paralysis and the impairment of the prognosis of the different tumour types is shown. The presence of preoperative facial nerve paralysis in malignant parotid tumours implies a very poor prognosis but the situation is not as hopeless as has been suggested and therefore one must rely on very radical surgery.", "contents": "Preoperative facial paralysis in malignant parotid tumours. Preoperative paralysis of the facial nerve was found in 145 of 1,029 patients with malignant parotid tumours (14%) treated at nine university clinics in Scandinavia. The incidence of facial paralysis varied between the different clinics. A parellelism between the incidence of the facial paralysis and the impairment of the prognosis of the different tumour types is shown. The presence of preoperative facial nerve paralysis in malignant parotid tumours implies a very poor prognosis but the situation is not as hopeless as has been suggested and therefore one must rely on very radical surgery."}
{"id": "PMID:206867", "title": "Isolation of blood and intracellular forms of Trypansoma cruzi from rats and other rodents and preliminary studies of their metabolism.", "content": "Isolation of blood and intracellular forms of Trypanosoma cruzi was made mainly from rats (90-110 g) which had received 580 rad of whole-body gamma-irradiation not more than 24 h before subcutaneous inoculation with 10(7) trypomastigotes of the Sonya strain of T. cruzi. Unirradiated chinchillas (250-350 g) were, however, used for some experiments. Blood forms were isolated using a technique involving differential centrifugation to remove most of the erythrocytes and DEAE-cellulose chromatography to remove the remaining blood cells. Overall recoveries were usually in the range 30-70%. Parasites were mainly (approximately 98%) broad forms and were motile, metabolically active (as judged by respiratory and radio-tracer incorporation studies) and had lost none of their infectivity for mice. Intracellular forms were isolated from hind-limb muscle tissue. This was disrupted in an MSE tissue homogenizer and the homogenate incubated with DNase, collagenase and trypsin. Parasites, contaminated only by a few blood cells, were then obtained by differential centrifugation. For purer preparations, a terminal sucrose gradient step was used. Recoveries ranged between 40 and 70%. About 1-3% of the parasites isolated were epimastigotes and trypomastigotes; the remainder are probably best collectively termed 'amastigotes', though they were pointed and most had a short, free flagellum. They were undamaged as judged by light and electron microscopy and metabolically active as judged by respiratory and radio-tracer incorporation studies. However, the infectivity for mice of both these purified preparations and the initial cell homogenates could be accounted for by the epimastigotes and trypomastigotes present in them. Preliminary biochemical studies with isolated parasites have shown that blood, intracellular and culture forms of T. cruzi have a respiratory system which is in part sensitive to CN- and that all forms synthesize nucleic acids and proteins when incubated in vitro. There appears, however, to be a lack of DNA synthesis in blood stages, and thus it is not surprising that these forms do not divide.", "contents": "Isolation of blood and intracellular forms of Trypansoma cruzi from rats and other rodents and preliminary studies of their metabolism. Isolation of blood and intracellular forms of Trypanosoma cruzi was made mainly from rats (90-110 g) which had received 580 rad of whole-body gamma-irradiation not more than 24 h before subcutaneous inoculation with 10(7) trypomastigotes of the Sonya strain of T. cruzi. Unirradiated chinchillas (250-350 g) were, however, used for some experiments. Blood forms were isolated using a technique involving differential centrifugation to remove most of the erythrocytes and DEAE-cellulose chromatography to remove the remaining blood cells. Overall recoveries were usually in the range 30-70%. Parasites were mainly (approximately 98%) broad forms and were motile, metabolically active (as judged by respiratory and radio-tracer incorporation studies) and had lost none of their infectivity for mice. Intracellular forms were isolated from hind-limb muscle tissue. This was disrupted in an MSE tissue homogenizer and the homogenate incubated with DNase, collagenase and trypsin. Parasites, contaminated only by a few blood cells, were then obtained by differential centrifugation. For purer preparations, a terminal sucrose gradient step was used. Recoveries ranged between 40 and 70%. About 1-3% of the parasites isolated were epimastigotes and trypomastigotes; the remainder are probably best collectively termed 'amastigotes', though they were pointed and most had a short, free flagellum. They were undamaged as judged by light and electron microscopy and metabolically active as judged by respiratory and radio-tracer incorporation studies. However, the infectivity for mice of both these purified preparations and the initial cell homogenates could be accounted for by the epimastigotes and trypomastigotes present in them. Preliminary biochemical studies with isolated parasites have shown that blood, intracellular and culture forms of T. cruzi have a respiratory system which is in part sensitive to CN- and that all forms synthesize nucleic acids and proteins when incubated in vitro. There appears, however, to be a lack of DNA synthesis in blood stages, and thus it is not surprising that these forms do not divide."}
{"id": "PMID:206868", "title": "Replication of Mouse Sarcoma Virus (Moloney) and its helper in a human heteroploid cell line of malignant origin.", "content": "A human heteroploid cell line of malignant origin (J111) was infected with Mouse Moloney Sarcoma Virus. [MSV-M(MLV)]. The replication of the virus was demonstrated by different methods. After a few passages of infected cultures, the transforming component of MSV-M(MLV) disappeared from the supernatant fluids and cells. The non transforming helper component continued to be produced. The relatively low amount of helper virus released by the cells suggests a control of its replication in the J111 cellular system.", "contents": "Replication of Mouse Sarcoma Virus (Moloney) and its helper in a human heteroploid cell line of malignant origin. A human heteroploid cell line of malignant origin (J111) was infected with Mouse Moloney Sarcoma Virus. [MSV-M(MLV)]. The replication of the virus was demonstrated by different methods. After a few passages of infected cultures, the transforming component of MSV-M(MLV) disappeared from the supernatant fluids and cells. The non transforming helper component continued to be produced. The relatively low amount of helper virus released by the cells suggests a control of its replication in the J111 cellular system."}
{"id": "PMID:206869", "title": "[Metyrapone test and plasma hormone estimations (author's transl)].", "content": "The usual metyrapone test based on the determination of the urinary steroid levels after ingestion of the product is relatively difficult to use because of its duration. In order to simplify this test, a comparative study was carried out with thirty subjects, 24 of whom were normal, by measuring their plasma hormonal levels by radioimmunoassay for ACTH, cortisol and aldosterone and by radiocompetition after extraction by carbon tetrachloride for the 11-desoxycortisol (S compound). The results show a parallel between the variation of the urinary steroid levels and the variations of plasma hormone levels during the first 24 hours of the test. Therefore, measuring the levels of ACTH, S compound and cortisol in the plasma before the ingestion of metyrapone and 24 hours afterwards seems simpler to carry out and accurate enough to test the integrity of the feed-back system between hypothalamus, pituitary and adrenal glands.", "contents": "[Metyrapone test and plasma hormone estimations (author's transl)]. The usual metyrapone test based on the determination of the urinary steroid levels after ingestion of the product is relatively difficult to use because of its duration. In order to simplify this test, a comparative study was carried out with thirty subjects, 24 of whom were normal, by measuring their plasma hormonal levels by radioimmunoassay for ACTH, cortisol and aldosterone and by radiocompetition after extraction by carbon tetrachloride for the 11-desoxycortisol (S compound). The results show a parallel between the variation of the urinary steroid levels and the variations of plasma hormone levels during the first 24 hours of the test. Therefore, measuring the levels of ACTH, S compound and cortisol in the plasma before the ingestion of metyrapone and 24 hours afterwards seems simpler to carry out and accurate enough to test the integrity of the feed-back system between hypothalamus, pituitary and adrenal glands."}
{"id": "PMID:206873", "title": "Cae I: an endonuclease isolated from the African green monkey with properties indicating site-specific cleavage of homologous and heterologous mammalian DNA.", "content": "Component alpha DNA is a highly repetitive sequence that comprises nearly a quarter of the African green monkey (Cercopithecus aethiops) genome. A previous microbial restriction enzyme analysis showed that the repeat structure of component alpha DNA is based upon a monomeric unit of 176 +/- 4 base-pairs. An endonuclease, provisionally termed Case I, has been isolated from African green monkey testes that cleaves component alpha DNA into multimeric segments based upon the same repeat periodicity as that revealed by microbial restriction enzymes. The primary sites of Cae I cleavage in the component alpha sequence appear to be 120 +/- 6 base-pairs distant from the Hind III sites and 73 +/- 6 base-pairs distant from the Eco RI* sites. Cae I has been partially characterized with special reference to the effects of ATP and S-adenosylmethionine on the cleavage of component alpha DNA. Cae I may be a member of a class of similar site-specific nucleases present in mammalian cells. Cae I also cleaves mouse satellite DNA into a multimeric series of discrete segments: the periodicity of this series is shorter than that revealed by Eco RII retriction analysis of mouse satellite DNA.", "contents": "Cae I: an endonuclease isolated from the African green monkey with properties indicating site-specific cleavage of homologous and heterologous mammalian DNA. Component alpha DNA is a highly repetitive sequence that comprises nearly a quarter of the African green monkey (Cercopithecus aethiops) genome. A previous microbial restriction enzyme analysis showed that the repeat structure of component alpha DNA is based upon a monomeric unit of 176 +/- 4 base-pairs. An endonuclease, provisionally termed Case I, has been isolated from African green monkey testes that cleaves component alpha DNA into multimeric segments based upon the same repeat periodicity as that revealed by microbial restriction enzymes. The primary sites of Cae I cleavage in the component alpha sequence appear to be 120 +/- 6 base-pairs distant from the Hind III sites and 73 +/- 6 base-pairs distant from the Eco RI* sites. Cae I has been partially characterized with special reference to the effects of ATP and S-adenosylmethionine on the cleavage of component alpha DNA. Cae I may be a member of a class of similar site-specific nucleases present in mammalian cells. Cae I also cleaves mouse satellite DNA into a multimeric series of discrete segments: the periodicity of this series is shorter than that revealed by Eco RII retriction analysis of mouse satellite DNA."}
{"id": "PMID:206874", "title": "The reactivity of phosphomono-and phosphodiester groups in oligonucleotides.", "content": "The rate constants were estimated by phosphorus NMR spectroscopy for the reactions of alcohols (Tr-dT, 2-cyanoethanol) in pyridine with the main types of the reactive phosphorylating intermediates formed by treatment of pdT-Ac, pdTpdT-Ac, Tr-dTpdT-Ac, Tr-dTpdTpdT-Ac with 2, 4, 6-triisopropylbenzene-sulfonyl chloride (TPS): 1) B type derivatives with phosphomono ester (PME) group converted to a phosphoryl pyridinium residue; 2) C type derivatives with PME and phosphodiester (PDE) groups converted to trisubstituted pyrophosphate; 3) D type derivatives with PDE groups converted to tetrasubstituted pyrophosphate. The two latter types are partially present as cyclic intramolecular pyrophosphates Ci and Di. The reactivity of the intermediates decrease in the series B greater than Ci approximately Di greater than C approximately D. The Ci derivative of pdTpdT-Ac when obtained in dimethylformamide was found to be rather stable to hydrolysis and could be separated from the other dinucleotide derivatives by ion-exchange chromatography. The Arrhenius parameters of all steps of the conversion of PME group of pdT-Ac to B derivative and of the reaction of TPS with PDE group of dinucleoside phosphate Tr-dTpdT-Ac were measured.", "contents": "The reactivity of phosphomono-and phosphodiester groups in oligonucleotides. The rate constants were estimated by phosphorus NMR spectroscopy for the reactions of alcohols (Tr-dT, 2-cyanoethanol) in pyridine with the main types of the reactive phosphorylating intermediates formed by treatment of pdT-Ac, pdTpdT-Ac, Tr-dTpdT-Ac, Tr-dTpdTpdT-Ac with 2, 4, 6-triisopropylbenzene-sulfonyl chloride (TPS): 1) B type derivatives with phosphomono ester (PME) group converted to a phosphoryl pyridinium residue; 2) C type derivatives with PME and phosphodiester (PDE) groups converted to trisubstituted pyrophosphate; 3) D type derivatives with PDE groups converted to tetrasubstituted pyrophosphate. The two latter types are partially present as cyclic intramolecular pyrophosphates Ci and Di. The reactivity of the intermediates decrease in the series B greater than Ci approximately Di greater than C approximately D. The Ci derivative of pdTpdT-Ac when obtained in dimethylformamide was found to be rather stable to hydrolysis and could be separated from the other dinucleotide derivatives by ion-exchange chromatography. The Arrhenius parameters of all steps of the conversion of PME group of pdT-Ac to B derivative and of the reaction of TPS with PDE group of dinucleoside phosphate Tr-dTpdT-Ac were measured."}
{"id": "PMID:206875", "title": "Cleavage of Epstein-Barr virus DNA by restriction endonucleases EcoRI, HindIII and BamI.", "content": "The cleavage of the DNAs of the B95-8 and P3HR-1 virus strains of Epstein-Barr virus by the restriction endonucleases EcoRI, HindIII and BamI was investigated using a new technique for quantitative evaluation of the fluorescence of ethidium stained DNA fragments separated on agarose gels. The results obtained with B95-8 DNA showed that in addition to the limited repetitions of nucleotide sequences observed in the EcoRI and HindIII cleavage patterns, the molecule contained a BamI fragment with a molecular mass of 2.0 megadaltons which was present in a total of about 11 copies and localized to a limited part of the DNA molecule. The same sequences were also present in the P3HR-1 DNA albeit in a lower molar ratio. P3HR-1 DNA yielded restriction enzyme cleavage patterns suggesting DNA sequence heterogeneity of P3HR-1 virus. No fragment was present in more than about 4 copies per molecule of P3HR-1 DNA. Comparison of the restriction enzyme cleavage patterns of P3HR-1 and B95-8 DNA revealed a high degree of structural homology emphasized by nucleic acid hybridization experiments with EBV complementary RNA synthesized in vitro.", "contents": "Cleavage of Epstein-Barr virus DNA by restriction endonucleases EcoRI, HindIII and BamI. The cleavage of the DNAs of the B95-8 and P3HR-1 virus strains of Epstein-Barr virus by the restriction endonucleases EcoRI, HindIII and BamI was investigated using a new technique for quantitative evaluation of the fluorescence of ethidium stained DNA fragments separated on agarose gels. The results obtained with B95-8 DNA showed that in addition to the limited repetitions of nucleotide sequences observed in the EcoRI and HindIII cleavage patterns, the molecule contained a BamI fragment with a molecular mass of 2.0 megadaltons which was present in a total of about 11 copies and localized to a limited part of the DNA molecule. The same sequences were also present in the P3HR-1 DNA albeit in a lower molar ratio. P3HR-1 DNA yielded restriction enzyme cleavage patterns suggesting DNA sequence heterogeneity of P3HR-1 virus. No fragment was present in more than about 4 copies per molecule of P3HR-1 DNA. Comparison of the restriction enzyme cleavage patterns of P3HR-1 and B95-8 DNA revealed a high degree of structural homology emphasized by nucleic acid hybridization experiments with EBV complementary RNA synthesized in vitro."}
{"id": "PMID:206876", "title": "Photochemical crosslinking of transcription complexes with psoralen. I. Covalent attachment of in vitro SV40 nascent RNA to its double-stranded DNA template.", "content": "14C-labeled SV40 DNA has been transcribed with E. coli RNA polymerase using 3H-labeled ribonucleotide triphosphates as precursors. The resulting transcription complexes were then photochemically crosslinked with the psoralen derivative, 4'-aminomethyl-4,5', 8-trimethylpsoralen (AMT), at 37 degrees C and analyzed in SDS-sucrose gradients. It was found that the photochemical crosslinking procedure caused the nascent RNA chains to co-sediment with their double-stranded (helical) SV40 templates in the denaturing sucrose gradient. This result and several control experiments suggest that covalent linkages have formed between nascent RNA and helical DNA after the photochemical reaction. The crosslinking phenomenon was observed to be independent of the superhelical state of the DNA used as the template. Prior addition of EDTA to stop the transcription is not required for successful crosslinkage.", "contents": "Photochemical crosslinking of transcription complexes with psoralen. I. Covalent attachment of in vitro SV40 nascent RNA to its double-stranded DNA template. 14C-labeled SV40 DNA has been transcribed with E. coli RNA polymerase using 3H-labeled ribonucleotide triphosphates as precursors. The resulting transcription complexes were then photochemically crosslinked with the psoralen derivative, 4'-aminomethyl-4,5', 8-trimethylpsoralen (AMT), at 37 degrees C and analyzed in SDS-sucrose gradients. It was found that the photochemical crosslinking procedure caused the nascent RNA chains to co-sediment with their double-stranded (helical) SV40 templates in the denaturing sucrose gradient. This result and several control experiments suggest that covalent linkages have formed between nascent RNA and helical DNA after the photochemical reaction. The crosslinking phenomenon was observed to be independent of the superhelical state of the DNA used as the template. Prior addition of EDTA to stop the transcription is not required for successful crosslinkage."}
{"id": "PMID:206878", "title": "Discharge of the premature infant.", "content": "Appropriate interventions are initiated smoothly if the neonatal staff is familiarized with the new concepts of infant care and their empirical basis. It is also important that the nurses be present at all conferences to facilitate more meaningful interaction with the mother and her infant. If this is done, then it is easier to evaluate the needs of the mother and how much teaching support is necessary. The more involved the nurse becomes with the family, the more rewarding her experience will be, and she will be eager to get involved with the next family.", "contents": "Discharge of the premature infant. Appropriate interventions are initiated smoothly if the neonatal staff is familiarized with the new concepts of infant care and their empirical basis. It is also important that the nurses be present at all conferences to facilitate more meaningful interaction with the mother and her infant. If this is done, then it is easier to evaluate the needs of the mother and how much teaching support is necessary. The more involved the nurse becomes with the family, the more rewarding her experience will be, and she will be eager to get involved with the next family."}
{"id": "PMID:206886", "title": "Common methionine-tryptic peptides near the amino-terminal end of primate papovavirus tumor antigens.", "content": "The tumor antigens directed by human papovaviruses BK and JC and the monkey papovavirus simian virus 40 have two methionine-containing tryptic peptides in common. These peptides are constituents of the small forms of papovavirus tumor antigen (17,000 daltons) which are present in lytically infected and transformed cells and which are believed to share some amino acid sequences with the amino-terminal portion of the larger tumor antigen species (97,000 daltons). In addition to the two peptides, which are present in all three papovavirus tumor antigens, the larger forms of the tumor antigens specified by simian virus 40 and BK virus share four other methionine-containing tryptic peptides, two of which are also present in the smaller (17,000 daltons) species of antigen. The occurrence of common peptides at the amino-terminal portion of tumor antigens of primate papovaviruses suggests that these conserved regions may play a fundamental role in the function of these proteins and in the propagation of these viruses in nature. The tryptic peptides of the small forms of papovavirus tumor antigen were examined and compared to those present in the large species. Out of a total of nine and ten methionine-containing peptides in the 17,000-dalton tumor antigens of simian virus 40 and BK virus, seven and nine peptides, respectively, are constituents of the corresponding larger (97,000 daltons) forms of the antigen.", "contents": "Common methionine-tryptic peptides near the amino-terminal end of primate papovavirus tumor antigens. The tumor antigens directed by human papovaviruses BK and JC and the monkey papovavirus simian virus 40 have two methionine-containing tryptic peptides in common. These peptides are constituents of the small forms of papovavirus tumor antigen (17,000 daltons) which are present in lytically infected and transformed cells and which are believed to share some amino acid sequences with the amino-terminal portion of the larger tumor antigen species (97,000 daltons). In addition to the two peptides, which are present in all three papovavirus tumor antigens, the larger forms of the tumor antigens specified by simian virus 40 and BK virus share four other methionine-containing tryptic peptides, two of which are also present in the smaller (17,000 daltons) species of antigen. The occurrence of common peptides at the amino-terminal portion of tumor antigens of primate papovaviruses suggests that these conserved regions may play a fundamental role in the function of these proteins and in the propagation of these viruses in nature. The tryptic peptides of the small forms of papovavirus tumor antigen were examined and compared to those present in the large species. Out of a total of nine and ten methionine-containing peptides in the 17,000-dalton tumor antigens of simian virus 40 and BK virus, seven and nine peptides, respectively, are constituents of the corresponding larger (97,000 daltons) forms of the antigen."}
{"id": "PMID:206887", "title": "Translational control by hemin is due to binding to cyclic AMP-dependent protein kinase.", "content": "Our previous work [Proc. Natl, Acad. Sci. USA (1977) 74, 1463-1467, 3326-3329] is consistent with the view that (a) the hemin-controlled inhibitor of protein synthesis in reticulocyte lysates (active eIF-2 kinase) is formed by phosphorylation of proinhibitor (inactive eIF-2 kinase) catalyzed by cyclic AMP-dependent protein kinase (ATP-protein phosphotransferase; EC 2.7.1.37), and (b) hemin prevents this conversion by blocking the interaction of cyclic AMP with the kinase's regulation subunit, thereby rendering the enzyme inactive. We now show that hemin blocks cyclic AMP binding because it itself binds specifically to the regulatory subunit. This binding is noncompetitive with respect to cyclic AMP. Whereas unlabeled hemin can displace bound [3H]hemin as well as cyclic [3H]AMP, unlabeled cyclic AMP can displace bound cyclic [3H]AMP but not [3H]hemin. This suggests that cyclic AMP and hemin bind to different sites on the protein and that hemin binding affects cyclic AMP binding in an allosteric manner.", "contents": "Translational control by hemin is due to binding to cyclic AMP-dependent protein kinase. Our previous work [Proc. Natl, Acad. Sci. USA (1977) 74, 1463-1467, 3326-3329] is consistent with the view that (a) the hemin-controlled inhibitor of protein synthesis in reticulocyte lysates (active eIF-2 kinase) is formed by phosphorylation of proinhibitor (inactive eIF-2 kinase) catalyzed by cyclic AMP-dependent protein kinase (ATP-protein phosphotransferase; EC 2.7.1.37), and (b) hemin prevents this conversion by blocking the interaction of cyclic AMP with the kinase's regulation subunit, thereby rendering the enzyme inactive. We now show that hemin blocks cyclic AMP binding because it itself binds specifically to the regulatory subunit. This binding is noncompetitive with respect to cyclic AMP. Whereas unlabeled hemin can displace bound [3H]hemin as well as cyclic [3H]AMP, unlabeled cyclic AMP can displace bound cyclic [3H]AMP but not [3H]hemin. This suggests that cyclic AMP and hemin bind to different sites on the protein and that hemin binding affects cyclic AMP binding in an allosteric manner."}
{"id": "PMID:206888", "title": "Fluorescent photoaffinity labeling: adenosine 3',5'-cyclic monophosphate receptor sites.", "content": "An approach to the study of protein receptor sites in protein mixtures or supramolecular assemblies by using fluorescence spectroscopy is described. This approach, fluorescent photoaffinity labeling, combines the merits of photoaffinity labeling to attain site-directed reactivity with the probing power of fluorescent ligands. A fluorescent photoaffinity label for cyclic AMP receptor sites of cyclic AMP-dependent protein kinases was synthesized in both unlabeled and radioactive forms. The probe, 8-azido-1,N(6)-ethenoadenosine 3',5'-cyclic monophosphate, mimics cyclic AMP in its ability to stimulate the phosphotransferase activity of the protein kinases and strongly competes with cyclic AMP for its binding sites in all preparations so far tested. Photolysis, after equilibration of protein kinase and 8-azido-1,N(6)-ethenoadenosine 3',5'-cyclic monophosphate in the dark, effects binding of the intermediate nitrene irreversibly and specifically to the cyclic AMP sites with the development of fluorescence. Excess reagent and low molecular weight photolytic products are removable by dialysis. Studies of a crude beef heart preparation containing cyclic AMP-dependent protein kinase suggest that the cyclic AMP binding sites are hydrophobic in nature and strongly immobilize the adenine moiety of the cyclic nucleotide.", "contents": "Fluorescent photoaffinity labeling: adenosine 3',5'-cyclic monophosphate receptor sites. An approach to the study of protein receptor sites in protein mixtures or supramolecular assemblies by using fluorescence spectroscopy is described. This approach, fluorescent photoaffinity labeling, combines the merits of photoaffinity labeling to attain site-directed reactivity with the probing power of fluorescent ligands. A fluorescent photoaffinity label for cyclic AMP receptor sites of cyclic AMP-dependent protein kinases was synthesized in both unlabeled and radioactive forms. The probe, 8-azido-1,N(6)-ethenoadenosine 3',5'-cyclic monophosphate, mimics cyclic AMP in its ability to stimulate the phosphotransferase activity of the protein kinases and strongly competes with cyclic AMP for its binding sites in all preparations so far tested. Photolysis, after equilibration of protein kinase and 8-azido-1,N(6)-ethenoadenosine 3',5'-cyclic monophosphate in the dark, effects binding of the intermediate nitrene irreversibly and specifically to the cyclic AMP sites with the development of fluorescence. Excess reagent and low molecular weight photolytic products are removable by dialysis. Studies of a crude beef heart preparation containing cyclic AMP-dependent protein kinase suggest that the cyclic AMP binding sites are hydrophobic in nature and strongly immobilize the adenine moiety of the cyclic nucleotide."}
{"id": "PMID:206889", "title": "Amphibian oocyte maturation and protein synthesis: related inhibition by cyclic AMP, theophylline, and papaverine.", "content": "Two inhibitors of cyclic AMP phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17), theophylline and papaverine, inhibit the maturation of Xenopus laevis oocytes induced by four different stimuli: human chorionic gonadotropin, progesterone, testosterone, and lanthanum ions. Addition of 1 mM cyclic AMP to the medium delays maturation by approximately 2 hr. Papaverine, theophylline, and cyclic AMP inhibit amino acid incorporation into oocyte proteins by 50% or more but do not inhibit amino acid uptake. The capacity of theophylline to block maturation and protein synthesis is reversed in a parallel fashion by addition of 1-5 mM calcium ion to the medium. Addition of papaverine, theophylline, and cycloheximide to oocytes at different times after hormonal treatment shows that the step sensitive to blockage by the three drugs is coincident and precedes germinal vesicle breakdown by about 1.5 hr. Theophylline and papaverine do not increase endogenous cyclic AMP levels in oocytes but do block the decrease of cyclic AMP levels observed 3 hr after progesterone treatment. Both drugs inhibit oocyte cyclic AMP phosphodiesterase measured in vivo and severely inhibit the stimulus of calcium uptake caused by progesterone and human chorionic gonadotropin. These results suggest that cyclic AMP, theophylline, and papaverine may block oocyte maturation by inhibiting protein synthesis, possibly via a cyclic AMP-dependent protein kinase as shown in reticulocytes [Datta, A., De Haro, C., Sierra, J. & Ochoa, S. (1977) Proc. Natl. Acad. Sci., USA 74, 1463-1467].", "contents": "Amphibian oocyte maturation and protein synthesis: related inhibition by cyclic AMP, theophylline, and papaverine. Two inhibitors of cyclic AMP phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17), theophylline and papaverine, inhibit the maturation of Xenopus laevis oocytes induced by four different stimuli: human chorionic gonadotropin, progesterone, testosterone, and lanthanum ions. Addition of 1 mM cyclic AMP to the medium delays maturation by approximately 2 hr. Papaverine, theophylline, and cyclic AMP inhibit amino acid incorporation into oocyte proteins by 50% or more but do not inhibit amino acid uptake. The capacity of theophylline to block maturation and protein synthesis is reversed in a parallel fashion by addition of 1-5 mM calcium ion to the medium. Addition of papaverine, theophylline, and cycloheximide to oocytes at different times after hormonal treatment shows that the step sensitive to blockage by the three drugs is coincident and precedes germinal vesicle breakdown by about 1.5 hr. Theophylline and papaverine do not increase endogenous cyclic AMP levels in oocytes but do block the decrease of cyclic AMP levels observed 3 hr after progesterone treatment. Both drugs inhibit oocyte cyclic AMP phosphodiesterase measured in vivo and severely inhibit the stimulus of calcium uptake caused by progesterone and human chorionic gonadotropin. These results suggest that cyclic AMP, theophylline, and papaverine may block oocyte maturation by inhibiting protein synthesis, possibly via a cyclic AMP-dependent protein kinase as shown in reticulocytes [Datta, A., De Haro, C., Sierra, J. & Ochoa, S. (1977) Proc. Natl. Acad. Sci., USA 74, 1463-1467]."}
{"id": "PMID:206890", "title": "Detection and kinetic behavior of preproinsulin in pancreatic islets.", "content": "Newly synthesized rat islet proteins have been analyzed by polyacrylamide slab gel electrophoresis and fluorography. A minor component having an apparent molecular weight of 11,100 was identified as preproinsulin by the sensitivity of its synthesis to glucose, the pattern of NH2-terminal leucine residues, and the rapidity of its appearance and disappearance during incubation of islets or islet cell tumors. A small amount of labeled peptide material which may represent the excised NH2-terminal extension of preproinsulin or its fragment was also detected. The kinetics of formation and processing of the preproinsulin fraction were complex, consisting of a rapidly turning over component having a half-life of about 1 min and a slower minor fraction that may have bypassed the normal cleavage process. The electrophoretic resolution of the preproinsulin and proinsulin fractions into two bands each is consistent with the presence of two closely related gene products in rat islets rather than intermediate stages in the processing of these peptides.", "contents": "Detection and kinetic behavior of preproinsulin in pancreatic islets. Newly synthesized rat islet proteins have been analyzed by polyacrylamide slab gel electrophoresis and fluorography. A minor component having an apparent molecular weight of 11,100 was identified as preproinsulin by the sensitivity of its synthesis to glucose, the pattern of NH2-terminal leucine residues, and the rapidity of its appearance and disappearance during incubation of islets or islet cell tumors. A small amount of labeled peptide material which may represent the excised NH2-terminal extension of preproinsulin or its fragment was also detected. The kinetics of formation and processing of the preproinsulin fraction were complex, consisting of a rapidly turning over component having a half-life of about 1 min and a slower minor fraction that may have bypassed the normal cleavage process. The electrophoretic resolution of the preproinsulin and proinsulin fractions into two bands each is consistent with the presence of two closely related gene products in rat islets rather than intermediate stages in the processing of these peptides."}
{"id": "PMID:206891", "title": "Spliced early mRNAs of simian virus 40.", "content": "Biochemical methods are presented for determining the structure of spliced RNAs present in cells at low concentrations. Two cytoplasmic spliced viral RNAs were detected in CV-1 cells during the early phase of simian virus 40 (SV40) infection. One is 2200 nucleotides in length and is composed of two parts, 330 and 1900 nucleotides, mapping from approximately 0.67 to approximately 0.60 and from approximately 0.54 to approximately 0.14, respectively, on the standard viral map. The other is 2500 nucleotides long and also is composed of two parts, 630 and 1900 nucleotides mapping from approximately 0.67 to approximately 0.54 and from approximately 0.54 to approximately 0.14, respectively. Correlation of the structure of these mRNAs with the structure of the early SV40 proteins, small T antigen (17,000 daltons) and large T antigen (90,000 daltons), determined by others suggests that: (i) translation of the 2500-nucleotide mRNA yields small T antigen; (ii) translation of the 2200-nucleotide mRNA proceeds through the splice point in the RNA to produce large T antigen (and thus large T antigen is encoded in two separate regions of the viral genome); and (iii) the DNA sequences between approximately 0.67 and approximately 0.60 present in both mRNAs are translated in the same reading frame in both mRNAs to yield two separate gene products that have the same NH(2)-terminal sequence. Therefore, expression of the early SV40 genes is partially controlled at the level of splicing of RNAs.", "contents": "Spliced early mRNAs of simian virus 40. Biochemical methods are presented for determining the structure of spliced RNAs present in cells at low concentrations. Two cytoplasmic spliced viral RNAs were detected in CV-1 cells during the early phase of simian virus 40 (SV40) infection. One is 2200 nucleotides in length and is composed of two parts, 330 and 1900 nucleotides, mapping from approximately 0.67 to approximately 0.60 and from approximately 0.54 to approximately 0.14, respectively, on the standard viral map. The other is 2500 nucleotides long and also is composed of two parts, 630 and 1900 nucleotides mapping from approximately 0.67 to approximately 0.54 and from approximately 0.54 to approximately 0.14, respectively. Correlation of the structure of these mRNAs with the structure of the early SV40 proteins, small T antigen (17,000 daltons) and large T antigen (90,000 daltons), determined by others suggests that: (i) translation of the 2500-nucleotide mRNA yields small T antigen; (ii) translation of the 2200-nucleotide mRNA proceeds through the splice point in the RNA to produce large T antigen (and thus large T antigen is encoded in two separate regions of the viral genome); and (iii) the DNA sequences between approximately 0.67 and approximately 0.60 present in both mRNAs are translated in the same reading frame in both mRNAs to yield two separate gene products that have the same NH(2)-terminal sequence. Therefore, expression of the early SV40 genes is partially controlled at the level of splicing of RNAs."}
{"id": "PMID:206892", "title": "Biological activity of purified simian virus 40 T antigen proteins.", "content": "Proteins related to simian virus 40 (SV40) T antigen uere isolated from cells infected with adenovirus 2/SV40 hybrids Ad2+D2 and Ad2+ND1 dp2 as well as from a line of human cells (SV80) transformed by SV40. The 96,000- and 107,000-dalton proteins of SV80 and Ad2+D2, after injection into the cytoplasm of cultured cells, rapidly accumulate in the nuclei, where they remain antigenically reactive for at least 20 hr and trigger DNA synthesis in quiescent cells. By contrast, the 23,000-dalton protein coded by Ad2+ND1 dp2 does not stimulate cellular DNA synthesis. However, all three purified proteins are able to provide helper function for the growth of adenovirus 2 in monkey cells. Thus, purified SV40 T antigen and proteins that share sequences with it retain the ability to carry out at least two functions associated with the product of the A gene of SV40.", "contents": "Biological activity of purified simian virus 40 T antigen proteins. Proteins related to simian virus 40 (SV40) T antigen uere isolated from cells infected with adenovirus 2/SV40 hybrids Ad2+D2 and Ad2+ND1 dp2 as well as from a line of human cells (SV80) transformed by SV40. The 96,000- and 107,000-dalton proteins of SV80 and Ad2+D2, after injection into the cytoplasm of cultured cells, rapidly accumulate in the nuclei, where they remain antigenically reactive for at least 20 hr and trigger DNA synthesis in quiescent cells. By contrast, the 23,000-dalton protein coded by Ad2+ND1 dp2 does not stimulate cellular DNA synthesis. However, all three purified proteins are able to provide helper function for the growth of adenovirus 2 in monkey cells. Thus, purified SV40 T antigen and proteins that share sequences with it retain the ability to carry out at least two functions associated with the product of the A gene of SV40."}
{"id": "PMID:206893", "title": "Evidence for splicing of avian sarcoma virus 5'-terminal genomic sequences into viral-specific RNA in infected cells.", "content": "The 5'-terminal nucleotide sequences of the avian sarcoma virus (ASV) genome are transcribed by the reverse transcriptase in vitro into a DNA transcript that represents the entire distance ( approximately 100 nucleotides) between the tRNA(Trp) primer molecule and the 5' terminus. We have used these DNA(100) transcripts in hybridization reactions with ASV-specific RNA from infected avian cells and find nucleotide sequences complementary to these transcripts on all of the various size classes of viral mRNA identified. Similar hybridization results were obtained with a specific DNA transcript complementary to viral genomic nucleotide sequences between the tRNA(Trp) primer molecule and up to, but not including, the terminal redundant sequences (DNA(70)), indicating that the observed hybridization of DNA(100) to all size classes of viral RNA in infected cells did not reflect hybridization of DNA(100) to the terminal redundant sequences at the 3' end of the viral genome. Escherichia coli RNase H hydrolysis of RNA.DNA hybrids consisting of genomic 35S RNA obtained from virus and DNA(100) transcripts indicated that viral genomic sequences complementary to these DNA transcripts were not present at sites distal to the ends of the RNA genome and therefore not adjacent to the corresponding gene sequences representing the various species of viral mRNA from infected cells. These studies suggest that the 5'-terminal genomic nucleotide sequences, or a portion thereof, are somehow added or \"spliced\" onto each ASV-specific mRNA species in infected cells either during or after transcription of proviral DNA for some as yet undetermined purpose.", "contents": "Evidence for splicing of avian sarcoma virus 5'-terminal genomic sequences into viral-specific RNA in infected cells. The 5'-terminal nucleotide sequences of the avian sarcoma virus (ASV) genome are transcribed by the reverse transcriptase in vitro into a DNA transcript that represents the entire distance ( approximately 100 nucleotides) between the tRNA(Trp) primer molecule and the 5' terminus. We have used these DNA(100) transcripts in hybridization reactions with ASV-specific RNA from infected avian cells and find nucleotide sequences complementary to these transcripts on all of the various size classes of viral mRNA identified. Similar hybridization results were obtained with a specific DNA transcript complementary to viral genomic nucleotide sequences between the tRNA(Trp) primer molecule and up to, but not including, the terminal redundant sequences (DNA(70)), indicating that the observed hybridization of DNA(100) to all size classes of viral RNA in infected cells did not reflect hybridization of DNA(100) to the terminal redundant sequences at the 3' end of the viral genome. Escherichia coli RNase H hydrolysis of RNA.DNA hybrids consisting of genomic 35S RNA obtained from virus and DNA(100) transcripts indicated that viral genomic sequences complementary to these DNA transcripts were not present at sites distal to the ends of the RNA genome and therefore not adjacent to the corresponding gene sequences representing the various species of viral mRNA from infected cells. These studies suggest that the 5'-terminal genomic nucleotide sequences, or a portion thereof, are somehow added or \"spliced\" onto each ASV-specific mRNA species in infected cells either during or after transcription of proviral DNA for some as yet undetermined purpose."}
{"id": "PMID:206894", "title": "Regulation of acetylcholine release from neuroblastoma x glioma hybrid cells.", "content": "Neuroblastoma x glioma NG108-15 hybrid cells exposed to N6, O2'-dibutyryladenosine 3':5'-cyclic monophosphate for several days release [3H]acetylcholine in response to serotonin, prostaglandin F2alpha, KCl, or veratridine. NG108-15 cells grown in the absence of dibutyrul cyclic AMP do not respond to an excitatory stimulus by releasing [3H]acetylcholine but can be shifted to a responsive state by treatment with dibutyryl cyclic AMP. Thus, the reactions that are required for acetylcholine release can be regulated in NG108-15 cells, thereby regulating the ability of cells to form synapses and the efficiency of synaptic communication.", "contents": "Regulation of acetylcholine release from neuroblastoma x glioma hybrid cells. Neuroblastoma x glioma NG108-15 hybrid cells exposed to N6, O2'-dibutyryladenosine 3':5'-cyclic monophosphate for several days release [3H]acetylcholine in response to serotonin, prostaglandin F2alpha, KCl, or veratridine. NG108-15 cells grown in the absence of dibutyrul cyclic AMP do not respond to an excitatory stimulus by releasing [3H]acetylcholine but can be shifted to a responsive state by treatment with dibutyryl cyclic AMP. Thus, the reactions that are required for acetylcholine release can be regulated in NG108-15 cells, thereby regulating the ability of cells to form synapses and the efficiency of synaptic communication."}
{"id": "PMID:206895", "title": "Mechanism of the rapid antigonadotropic action of prostaglandins in cultured luteal cells.", "content": "A reproducible method for dissociation and culture of rat luteal cells is described. The concentration of LH required to produce half-maximal stimulation of progesterone secretion was 50 ng/ml. The effects of prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) on basal and luteinizing hormone (LH)-stimulated progesterone production were examined. Both prostaglandins stimulated basal progesterone production but PGE(2) was about twice as active, showing a 2-fold maximal stimulation at 0.75 muM. When either prostaglandin was incubated simultaneously with LH, a dose-dependent inhibition of progesterone secretion occurred; PGF(2alpha) was 4 times more active than PGE(2), showing 50% inhibition at a concentration of 40 x nM. Thus, both prostaglandins are more active as antagonists than as agonists of LH with respect to progesterone secretion. PGF(2alpha) also inhibited LH-stimulated adenylate cyclase activity and cyclic AMP accumulation. The block in progesterone secretion was reversed by addition of dibutyryl cyclic AMP (1 mM) but not by theophylline (5 mM) alone. These data and the finding that PGF(2alpha) did not affect the specific binding activity of the LH receptor in intact luteal cells indicate that the rapid action of prostaglandins in luteal cells is due to a block of LH-dependent production of cyclic AMP which results in a decrease in progesterone secretion.", "contents": "Mechanism of the rapid antigonadotropic action of prostaglandins in cultured luteal cells. A reproducible method for dissociation and culture of rat luteal cells is described. The concentration of LH required to produce half-maximal stimulation of progesterone secretion was 50 ng/ml. The effects of prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)) on basal and luteinizing hormone (LH)-stimulated progesterone production were examined. Both prostaglandins stimulated basal progesterone production but PGE(2) was about twice as active, showing a 2-fold maximal stimulation at 0.75 muM. When either prostaglandin was incubated simultaneously with LH, a dose-dependent inhibition of progesterone secretion occurred; PGF(2alpha) was 4 times more active than PGE(2), showing 50% inhibition at a concentration of 40 x nM. Thus, both prostaglandins are more active as antagonists than as agonists of LH with respect to progesterone secretion. PGF(2alpha) also inhibited LH-stimulated adenylate cyclase activity and cyclic AMP accumulation. The block in progesterone secretion was reversed by addition of dibutyryl cyclic AMP (1 mM) but not by theophylline (5 mM) alone. These data and the finding that PGF(2alpha) did not affect the specific binding activity of the LH receptor in intact luteal cells indicate that the rapid action of prostaglandins in luteal cells is due to a block of LH-dependent production of cyclic AMP which results in a decrease in progesterone secretion."}
{"id": "PMID:206896", "title": "Expression of collagen biosynthetic activities in lymphocytic cells.", "content": "Immunoglobulin-producing Merwin plasma cells, MPC-11, have been found to contain proplyl hydroxylase (prolyl-glycyl-peptide,2-oxoglutarate:oxygen oxidoreductase; EC 1.14.11.2) activity and its crossreacting protein, as well as hydroxyproline and a collagenous protein that could not be classified as type I, II, or III collagen. Friend leukemic cells, on the other hand, contained only prolyl hydroxylase. Thymus-derived (T) lymphocytes and bone-marrow-derived (B) lymphocytes freshly isolated from BALB/c mice expressed low but significant prolyl hydroxylase activity. Upon stimulation with phytohemagglutinin, the enzyme activity in T cells increased 22- to 29-fold. Crossreacting protein was also increased and appeared more stable than the prolyl hydroxylase. The effect of lipopolysaccharide stimulation on B cells uas similar but not as pronounced. Thus, even when not accompanied by other collagen biosynthetic activities, prolyl hydroxylase is present in all cells of hematologic origin.", "contents": "Expression of collagen biosynthetic activities in lymphocytic cells. Immunoglobulin-producing Merwin plasma cells, MPC-11, have been found to contain proplyl hydroxylase (prolyl-glycyl-peptide,2-oxoglutarate:oxygen oxidoreductase; EC 1.14.11.2) activity and its crossreacting protein, as well as hydroxyproline and a collagenous protein that could not be classified as type I, II, or III collagen. Friend leukemic cells, on the other hand, contained only prolyl hydroxylase. Thymus-derived (T) lymphocytes and bone-marrow-derived (B) lymphocytes freshly isolated from BALB/c mice expressed low but significant prolyl hydroxylase activity. Upon stimulation with phytohemagglutinin, the enzyme activity in T cells increased 22- to 29-fold. Crossreacting protein was also increased and appeared more stable than the prolyl hydroxylase. The effect of lipopolysaccharide stimulation on B cells uas similar but not as pronounced. Thus, even when not accompanied by other collagen biosynthetic activities, prolyl hydroxylase is present in all cells of hematologic origin."}
{"id": "PMID:206897", "title": "Amino- and carboxyl-terminal amino acid sequences of proteins coded by gag gene of murine leukemia virus.", "content": "The amino- and carboxyl-terminal amino acid sequences of proteins (p10, p12, p15, and p30) coded by the gag gene of Rauscher and AKR murine leukemia viruses were determined. Among these proteins, p15 from both viruses appears to have a blocked amino end. Proline was found to be the common NH(2) terminus of both p30s and both p12s, and alanine of both p10s. The amino-terminal sequences of p30s are identical, as are those of p10s, while the p12 sequences are clearly distinctive but also show substantial homology. The carboxyl-terminal amino acids of both viral p30s and p12s are leucine and phenylalanine, respectively. Rauscher leukemia virus p15 has tyrosine as the carboxyl terminus while AKR virus p15 has phenylalanine in this position. The compositional and sequence data provide definite chemical criteria for the identification of analogous gag gene products and for the comparison of viral proteins isolated in different laboratories. On the basis of amino acid sequences and the previously proposed H-p15-p12-p30-p10-COOH peptide sequence in the precursor polyprotein, a model for cleavage sites involved in the post-translational processing of the precursor coded for by the gag gene is proposed.", "contents": "Amino- and carboxyl-terminal amino acid sequences of proteins coded by gag gene of murine leukemia virus. The amino- and carboxyl-terminal amino acid sequences of proteins (p10, p12, p15, and p30) coded by the gag gene of Rauscher and AKR murine leukemia viruses were determined. Among these proteins, p15 from both viruses appears to have a blocked amino end. Proline was found to be the common NH(2) terminus of both p30s and both p12s, and alanine of both p10s. The amino-terminal sequences of p30s are identical, as are those of p10s, while the p12 sequences are clearly distinctive but also show substantial homology. The carboxyl-terminal amino acids of both viral p30s and p12s are leucine and phenylalanine, respectively. Rauscher leukemia virus p15 has tyrosine as the carboxyl terminus while AKR virus p15 has phenylalanine in this position. The compositional and sequence data provide definite chemical criteria for the identification of analogous gag gene products and for the comparison of viral proteins isolated in different laboratories. On the basis of amino acid sequences and the previously proposed H-p15-p12-p30-p10-COOH peptide sequence in the precursor polyprotein, a model for cleavage sites involved in the post-translational processing of the precursor coded for by the gag gene is proposed."}
{"id": "PMID:206898", "title": "Human placental cells transformed by tsA mutants of simian virus 40: a model system for the study of placental functions.", "content": "Human placental cells were transformed with wild-type simian virus 40 (SV40) and temperature-sensitive SV40 mutants of the A and B classes. Four criteria for transformation were used: decreased generation time, increased saturation density, increased efficiency of growth on plastic, and ability to overgrow a nontransformed monolayer. Cell lines transformed by tsA mutants lost the transformed phenotype at the restrictive temperature (40 degrees); therefore, the A function of SV40 is required for the maintenance of the transformed phenotype activity, an inhibition of human chorionic gonadotropin synthesis, and an increase in thymidine kinase activity were seen when human placental cells transformed by wild-type or tsB mutants of SV40 were grown at 33 degrees or 40 degrees and when tsA transformants were grown at 33 degrees. When tsA transformants were grown at 40 degrees, alkaline phosphatase activity and human chorionic gonadotropin synthesis were greatly stimulated and thymidine kinase activity was greatly reduced, approximating their levels in the placenta.", "contents": "Human placental cells transformed by tsA mutants of simian virus 40: a model system for the study of placental functions. Human placental cells were transformed with wild-type simian virus 40 (SV40) and temperature-sensitive SV40 mutants of the A and B classes. Four criteria for transformation were used: decreased generation time, increased saturation density, increased efficiency of growth on plastic, and ability to overgrow a nontransformed monolayer. Cell lines transformed by tsA mutants lost the transformed phenotype at the restrictive temperature (40 degrees); therefore, the A function of SV40 is required for the maintenance of the transformed phenotype activity, an inhibition of human chorionic gonadotropin synthesis, and an increase in thymidine kinase activity were seen when human placental cells transformed by wild-type or tsB mutants of SV40 were grown at 33 degrees or 40 degrees and when tsA transformants were grown at 33 degrees. When tsA transformants were grown at 40 degrees, alkaline phosphatase activity and human chorionic gonadotropin synthesis were greatly stimulated and thymidine kinase activity was greatly reduced, approximating their levels in the placenta."}
{"id": "PMID:206899", "title": "Chromosome mapping of the CYC7 gene determining yeast iso-2-cytochrome c: structural and regulatory regions.", "content": "The primary structures of iso-1-cytochrome c and iso-2-cytochrome c in the yeast Saccharomyces cerevisiae are determined by the genes CYC1 and CYC7, respectively. The CYC1 locus was previously shown to be on the right arm of chromosome X, and the CYC7 locus is shown in this investigation to be on the left arm of chromosome V closely linked to the min1 and mak10 markers. The CYC7 locus appears to be composed of a structural region and a regulatory region. Mutations in the structural region can cause a deficiency or alteration of iso-2-cytochrome c, whereas mutations in the regulatory region can cause increases in the amount of iso-2-cytochrome c. Single-site gene conversion, occurring at a relatively high frequency of approximately 4%, caused intragenic recombination of a mutational site in the structural region and a mutational site in the regulatory region, enabling us to suggest the order of the sites in relationship to other markers on the chromosome.", "contents": "Chromosome mapping of the CYC7 gene determining yeast iso-2-cytochrome c: structural and regulatory regions. The primary structures of iso-1-cytochrome c and iso-2-cytochrome c in the yeast Saccharomyces cerevisiae are determined by the genes CYC1 and CYC7, respectively. The CYC1 locus was previously shown to be on the right arm of chromosome X, and the CYC7 locus is shown in this investigation to be on the left arm of chromosome V closely linked to the min1 and mak10 markers. The CYC7 locus appears to be composed of a structural region and a regulatory region. Mutations in the structural region can cause a deficiency or alteration of iso-2-cytochrome c, whereas mutations in the regulatory region can cause increases in the amount of iso-2-cytochrome c. Single-site gene conversion, occurring at a relatively high frequency of approximately 4%, caused intragenic recombination of a mutational site in the structural region and a mutational site in the regulatory region, enabling us to suggest the order of the sites in relationship to other markers on the chromosome."}
{"id": "PMID:206900", "title": "Transfection of Fv-1 permissive and restrictive mouse cells with integrated DNA of murine leukemia viruses.", "content": "Whole-cell DNA preparations isolated from SC-1 cells chronically infected with N- or B-tropic murine leukemia viruses (MuLV) were tested for infectious activity in an Fv-1n (NIH-3T3) and two Fv-Ib (C57BL/6 and SV-A31) cell cultures. Efficiency of transfection for all DNAs was better in the NIH-3T3 cells than in C57BL/6 or SV-A31 cells; and an [N-tropic MuLV]SC-1 cell DNA preparation was slightly more infectious than a [B-tropic MuLV]SC-1 cell DNA preparation in all three cell cultures, regardless of their Fv-1 genotypes. Progeny viruses from the transfection showed N- or B-tropism corresponding to that of the parent viruses produced by the infected SC-1 cells that were used for the DNA preparation. DNA dose-response studies in NIH-3T3 cells revealed a one-hit mechanism for both the [B-tropic MuLV]SC-1 cell DNA and the [N-tropic MuLV]SC-1 cell DNA preparation. These results demonstrate that, in contrast to virion infection, transfection of N- and B-tropic MuLV with DNA preparations from chronically infected cells is not affected by the Fv-1 gene.", "contents": "Transfection of Fv-1 permissive and restrictive mouse cells with integrated DNA of murine leukemia viruses. Whole-cell DNA preparations isolated from SC-1 cells chronically infected with N- or B-tropic murine leukemia viruses (MuLV) were tested for infectious activity in an Fv-1n (NIH-3T3) and two Fv-Ib (C57BL/6 and SV-A31) cell cultures. Efficiency of transfection for all DNAs was better in the NIH-3T3 cells than in C57BL/6 or SV-A31 cells; and an [N-tropic MuLV]SC-1 cell DNA preparation was slightly more infectious than a [B-tropic MuLV]SC-1 cell DNA preparation in all three cell cultures, regardless of their Fv-1 genotypes. Progeny viruses from the transfection showed N- or B-tropism corresponding to that of the parent viruses produced by the infected SC-1 cells that were used for the DNA preparation. DNA dose-response studies in NIH-3T3 cells revealed a one-hit mechanism for both the [B-tropic MuLV]SC-1 cell DNA and the [N-tropic MuLV]SC-1 cell DNA preparation. These results demonstrate that, in contrast to virion infection, transfection of N- and B-tropic MuLV with DNA preparations from chronically infected cells is not affected by the Fv-1 gene."}
{"id": "PMID:206901", "title": "Association of cyclic GMP with gene expression of polytene chromosomes of Drosophila melanogaster.", "content": "The distribution of cyclic nucleotides on polytene chromosomes isolated from Drosophilia melanogaster salivary glands was examined by using an indirect immunofluorescent technique. With a fixative that minimized the loss of chromosomal proteins, cyclic GMP, but not cyclic AMP, was observed distributed along the chromosomes. The subchromosomal distribution of cyclic GMP correlated with genetically active sites on the chromosomes. After heat-shock treatments, the intensity of cyclic GMP fluorescence was markedly enhanced at specific loci on the chromosomes, with locus 93D as the most intensely fluorescent. Autoradiographic analysis with [3H]uridine revealed that 93D was the most transcriptionally active locus within a particular nucleus. These observations suggest that cyclic GMP may participate in processes associated with transcription on polytene chromosomes. The involvement of cyclic GMP in nuclear events associated with gene expression is discussed.", "contents": "Association of cyclic GMP with gene expression of polytene chromosomes of Drosophila melanogaster. The distribution of cyclic nucleotides on polytene chromosomes isolated from Drosophilia melanogaster salivary glands was examined by using an indirect immunofluorescent technique. With a fixative that minimized the loss of chromosomal proteins, cyclic GMP, but not cyclic AMP, was observed distributed along the chromosomes. The subchromosomal distribution of cyclic GMP correlated with genetically active sites on the chromosomes. After heat-shock treatments, the intensity of cyclic GMP fluorescence was markedly enhanced at specific loci on the chromosomes, with locus 93D as the most intensely fluorescent. Autoradiographic analysis with [3H]uridine revealed that 93D was the most transcriptionally active locus within a particular nucleus. These observations suggest that cyclic GMP may participate in processes associated with transcription on polytene chromosomes. The involvement of cyclic GMP in nuclear events associated with gene expression is discussed."}
{"id": "PMID:206902", "title": "Pseudotypes of feline sarcoma virus contain an 85,000-dalton protein with feline oncornavirus-associated cell membrane antigen (FOCMA) activity.", "content": "Feline sarcoma virus (FeSV) rescued from transformed nonproducer mink or rat cells contains two FeSV-specific antigens (p15 and p12), and the feline oncornavirus-associated cell membrane antigen (FOCMA). All three antigens are helper virus-independent and are encoded by the FeSV genome, FOCMA, p15, and p12 antigens cochromatograph as phosphorylated molecules of 85,000 molecular weight (pp85), adsorb to immunoadsorbant columns prepared with antibodies to feline leukemia virus (FeLV), and are precipitated with antisera to FeLV or FOCMA. Antibodies to FOCMA can be adsorbed with fractions containing pp85 but not with FeLV proteins, including p15 and p12. Thus, a virus-coded tumor antigen which immunizes cats against tumors induced by feline type C viruses is packaged in FeSV particles and is linked to viral structural protein.", "contents": "Pseudotypes of feline sarcoma virus contain an 85,000-dalton protein with feline oncornavirus-associated cell membrane antigen (FOCMA) activity. Feline sarcoma virus (FeSV) rescued from transformed nonproducer mink or rat cells contains two FeSV-specific antigens (p15 and p12), and the feline oncornavirus-associated cell membrane antigen (FOCMA). All three antigens are helper virus-independent and are encoded by the FeSV genome, FOCMA, p15, and p12 antigens cochromatograph as phosphorylated molecules of 85,000 molecular weight (pp85), adsorb to immunoadsorbant columns prepared with antibodies to feline leukemia virus (FeLV), and are precipitated with antisera to FeLV or FOCMA. Antibodies to FOCMA can be adsorbed with fractions containing pp85 but not with FeLV proteins, including p15 and p12. Thus, a virus-coded tumor antigen which immunizes cats against tumors induced by feline type C viruses is packaged in FeSV particles and is linked to viral structural protein."}
{"id": "PMID:206903", "title": "Repertoire of antiviral antibodies expressed by somatic cell hybrids.", "content": "Fusion between P3 x 63 Ag8 mouse myeloma cells and spleen cells from BALB/c mice immunized with influenza type A or B or parainfluenza type 1 virus generated reproducibly antiviral antibody-producing somatic cell hybrids (hybridomas). Eleven hybridomas derived from spleen cells of mice immunized with influenza type A virus were directed against the viral hemagglutinin, one reacted with a host component derived from chickens, and one expressed a specificity not further characterized. The hybridoma antibodies tended to be highly specific for the hemagglutinin of the immunizing virus and seemed to express the same repertoire of strain-specific antibody reactivities as splenic precursor B cells, they did not express any of the frequently occurring crossreactive anti-hemagglutinin specificities. Hybridomas producing crossreactive antibodies against hemagglutinin could be obtained if priming and boosting virus were heterologous.", "contents": "Repertoire of antiviral antibodies expressed by somatic cell hybrids. Fusion between P3 x 63 Ag8 mouse myeloma cells and spleen cells from BALB/c mice immunized with influenza type A or B or parainfluenza type 1 virus generated reproducibly antiviral antibody-producing somatic cell hybrids (hybridomas). Eleven hybridomas derived from spleen cells of mice immunized with influenza type A virus were directed against the viral hemagglutinin, one reacted with a host component derived from chickens, and one expressed a specificity not further characterized. The hybridoma antibodies tended to be highly specific for the hemagglutinin of the immunizing virus and seemed to express the same repertoire of strain-specific antibody reactivities as splenic precursor B cells, they did not express any of the frequently occurring crossreactive anti-hemagglutinin specificities. Hybridomas producing crossreactive antibodies against hemagglutinin could be obtained if priming and boosting virus were heterologous."}
{"id": "PMID:206904", "title": "Detection of viral proteins in mouse mammary tumors by immunoperoxidase staining of paraffin sections.", "content": "An indirect immunoperoxidase method is described, which can readily detect viral antigens in paraffin sections of primary, transplanted, and metastatic mammary tumors of mice. In addition to having the obvious advantage of not being limited to fresh specimens, immunoperoxidase staining of paraffin sections proved to be superior in many respects when compared with immunofluorescence and frozen sections. Immunoperoxidase staining of paraffin sections is permanent and provides the kind of histological detail required for precise cytological identification and localization with light microscopy. All of 25 tumors and 4 metastatic lesions showed evidence of glycoprotein gp52 as well as other mouse mammary tumor viral antigens. The pattern and intensity of the stain were related to the degree of histologic differentiation of the tumor. Wide variations in expression of viral antigens by individual malignant cells were observed within the same tumor.", "contents": "Detection of viral proteins in mouse mammary tumors by immunoperoxidase staining of paraffin sections. An indirect immunoperoxidase method is described, which can readily detect viral antigens in paraffin sections of primary, transplanted, and metastatic mammary tumors of mice. In addition to having the obvious advantage of not being limited to fresh specimens, immunoperoxidase staining of paraffin sections proved to be superior in many respects when compared with immunofluorescence and frozen sections. Immunoperoxidase staining of paraffin sections is permanent and provides the kind of histological detail required for precise cytological identification and localization with light microscopy. All of 25 tumors and 4 metastatic lesions showed evidence of glycoprotein gp52 as well as other mouse mammary tumor viral antigens. The pattern and intensity of the stain were related to the degree of histologic differentiation of the tumor. Wide variations in expression of viral antigens by individual malignant cells were observed within the same tumor."}
{"id": "PMID:206905", "title": "Detection in human breast carcinomas of an antigen immunologically related to a group-specific antigen of mouse mammary tumor virus.", "content": "An antigen immunologically related to a group-specific antigen (gp52, a 52,000-dalton glycoprotein) of the mouse mammary tumor virus has been identified in paraffin sections of human breast cancers by means of the indirect immunoperoxidase technique. The specificity of the reaction with antibody against mouse mammary tumor virus was examined by absorption of the IgG with the following: (a) purified gp52; (b) a number of virus preparations (mouse mammary tumor virus, Rauscher leukemia virus, simian sarcoma virus, baboon endogenous virus, and Mason-Pfizer monkey virus); (c) normal plasma, leukocytes, breast tissue, milk, actin, collagen, and hyaluronic acid, all of human origin; (d) sheep erythrocytes and mucin. Only mouse mammary tumor virus (from C(3)H or Paris RIII strains and grown in either murine or feline cells) and purified gp52 eliminated the immunohistochemical reaction in the human breast tumors. Positive reactions were seen in 51 of 131 (39%) breast carcinomas of various histologic types, a minimal estimate in view of the limited number of sections from each tumor that could be examined. Negative reactions were obtained in all 119 benign breast lesions (cystic disease, fibroadenoma, papilloma, gynecomastia) and in all 18 normal breast tissues. With one exception, 99 carcinomas from 13 organs other than breast and 8 cystosarcomas were all negative.", "contents": "Detection in human breast carcinomas of an antigen immunologically related to a group-specific antigen of mouse mammary tumor virus. An antigen immunologically related to a group-specific antigen (gp52, a 52,000-dalton glycoprotein) of the mouse mammary tumor virus has been identified in paraffin sections of human breast cancers by means of the indirect immunoperoxidase technique. The specificity of the reaction with antibody against mouse mammary tumor virus was examined by absorption of the IgG with the following: (a) purified gp52; (b) a number of virus preparations (mouse mammary tumor virus, Rauscher leukemia virus, simian sarcoma virus, baboon endogenous virus, and Mason-Pfizer monkey virus); (c) normal plasma, leukocytes, breast tissue, milk, actin, collagen, and hyaluronic acid, all of human origin; (d) sheep erythrocytes and mucin. Only mouse mammary tumor virus (from C(3)H or Paris RIII strains and grown in either murine or feline cells) and purified gp52 eliminated the immunohistochemical reaction in the human breast tumors. Positive reactions were seen in 51 of 131 (39%) breast carcinomas of various histologic types, a minimal estimate in view of the limited number of sections from each tumor that could be examined. Negative reactions were obtained in all 119 benign breast lesions (cystic disease, fibroadenoma, papilloma, gynecomastia) and in all 18 normal breast tissues. With one exception, 99 carcinomas from 13 organs other than breast and 8 cystosarcomas were all negative."}
{"id": "PMID:206906", "title": "Characterization of two types of human papillomaviruses in lesions of epidermodysplasia verruciformis.", "content": "Human papillomaviruses (HPVs) found in lesions of 11 patients suffering from epidermodysplasia verruciformis were compared to HPV type 1 (HPV-1) and HPV type 2 (HPV-2) previously characterized in plantar and common warts, respectively. Complementary RNAs (cRNAs) to HPV-1, HPV-2, and viruses obtained from two patients with epidermodysplasia verruciformis (J.D. HPV and J.K. HPV) were used in cRNA.DNA filter hybridization experiments. No sequence homology was detected between HPV-1 or HPV-2 DNAs and DNAs obtained from the 11 epidermodysplasia verruciformis HPV isolates. Furthermore, with J.D. and J.K. HPV cRNAs, epidermodysplasia verruciformis HPV DNAs fell into two groups showing little, if any, sequence homology. A lower extent of annealing was observed for the DNAs of some isolates showing a genetic heterogeneity within each of the two groups. Almost no antigenic crossreaction was detected by immunodiffusion and indirect immunofluorescence tests, either between epidermodysplasia verruciformis HPVs and HPV-1 or HPV-2 or between J.D. and J.K. HPVs. Viruses belonging to the same group have common antigenic properties, but antigenic differences were observed when two of the viruses sharing only partial DNA sequence homology were compared. Viruses related to J.D. HPV were preferentially associated with flat wart-like lesions of epidermodysplasia verruciformis and were further found in the lesions of five patients bearing multiple flat warts. Viruses related to J.K. HPV were found in morphologically distinct lesions (red spots) present in some patients with epidermodysplasia verruciformis. Thus, we propose to distinguish two other types of HPVs designated provisionally as HPV type 3 (HPV-3) and HPV type 4 (HPV-4), with J.D. and J.K. HPVs as prototypes, respectively. Malignant conversion of some epidermodysplasia verruciformis lesions is more frequently associated with HPV-4 than with HPV-3 infection.", "contents": "Characterization of two types of human papillomaviruses in lesions of epidermodysplasia verruciformis. Human papillomaviruses (HPVs) found in lesions of 11 patients suffering from epidermodysplasia verruciformis were compared to HPV type 1 (HPV-1) and HPV type 2 (HPV-2) previously characterized in plantar and common warts, respectively. Complementary RNAs (cRNAs) to HPV-1, HPV-2, and viruses obtained from two patients with epidermodysplasia verruciformis (J.D. HPV and J.K. HPV) were used in cRNA.DNA filter hybridization experiments. No sequence homology was detected between HPV-1 or HPV-2 DNAs and DNAs obtained from the 11 epidermodysplasia verruciformis HPV isolates. Furthermore, with J.D. and J.K. HPV cRNAs, epidermodysplasia verruciformis HPV DNAs fell into two groups showing little, if any, sequence homology. A lower extent of annealing was observed for the DNAs of some isolates showing a genetic heterogeneity within each of the two groups. Almost no antigenic crossreaction was detected by immunodiffusion and indirect immunofluorescence tests, either between epidermodysplasia verruciformis HPVs and HPV-1 or HPV-2 or between J.D. and J.K. HPVs. Viruses belonging to the same group have common antigenic properties, but antigenic differences were observed when two of the viruses sharing only partial DNA sequence homology were compared. Viruses related to J.D. HPV were preferentially associated with flat wart-like lesions of epidermodysplasia verruciformis and were further found in the lesions of five patients bearing multiple flat warts. Viruses related to J.K. HPV were found in morphologically distinct lesions (red spots) present in some patients with epidermodysplasia verruciformis. Thus, we propose to distinguish two other types of HPVs designated provisionally as HPV type 3 (HPV-3) and HPV type 4 (HPV-4), with J.D. and J.K. HPVs as prototypes, respectively. Malignant conversion of some epidermodysplasia verruciformis lesions is more frequently associated with HPV-4 than with HPV-3 infection."}
{"id": "PMID:206907", "title": "Development of a spin assay for reserve bilirubin loading capacity of human serum.", "content": "The capacity of human serum albumin to bind bilirubin is of paramount importance in the prevention of neurological damage due to hyperbilirubinemia in the neonate. Currently, there is no rapid, reliable method to determine the reserve bilirubin loading capacity of serum albumin. A method using electron spin resonance spectroscopy with a dianionic spin-label molecular probe [1-N-(2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl)-5-N-(1-aspartate)-2,4-dinitrobenzene] is presented which yields the reserve binding capacity of the bilirubin high-affinity binding site on human serum albumin and reserve bilirubin loading capacity of serum in mg/dl. Clinical validation of this spin assay may improve the neonatal care of jaundiced newborns.", "contents": "Development of a spin assay for reserve bilirubin loading capacity of human serum. The capacity of human serum albumin to bind bilirubin is of paramount importance in the prevention of neurological damage due to hyperbilirubinemia in the neonate. Currently, there is no rapid, reliable method to determine the reserve bilirubin loading capacity of serum albumin. A method using electron spin resonance spectroscopy with a dianionic spin-label molecular probe [1-N-(2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl)-5-N-(1-aspartate)-2,4-dinitrobenzene] is presented which yields the reserve binding capacity of the bilirubin high-affinity binding site on human serum albumin and reserve bilirubin loading capacity of serum in mg/dl. Clinical validation of this spin assay may improve the neonatal care of jaundiced newborns."}
{"id": "PMID:206908", "title": "Morphine sulfate stimulates the adenylate cyclase in mouse caudate nuclei.", "content": "The effect of several concentrations of morphine on the activity of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing): EC 4.6.1.1.] was measured in homogenates of caudate nuclei of mice. Morphine stimulated the enzyme at 500 micron and inhibited slightly at 5 micron. Morphine stimulation was blocked by naloxone. Depending on its dose, morphine also increased or decreased the stimulating effect of dopamine on the dopamine-sensitive adenylate cyclase activity of caudate homogenate. Like dopamine, morphine'e effect on the adenylate cyclase activity was increased or decreased, respectively, by pretreating the animals with poly(I).poly(C) or with chloramphenicol. Thus, both dopamine and morphine appear to act on the same receptor. This \"new\" receptor differs from the one described by Snyder et al. and others, who demonstrated only binding affinity and no enzymatic activity. These data indicate that certain functions of the opiates might be mediated through the dopamine-sensitive adenylate cyclase of the caudate nuclei, which are the dopamine receptors in the brain.", "contents": "Morphine sulfate stimulates the adenylate cyclase in mouse caudate nuclei. The effect of several concentrations of morphine on the activity of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing): EC 4.6.1.1.] was measured in homogenates of caudate nuclei of mice. Morphine stimulated the enzyme at 500 micron and inhibited slightly at 5 micron. Morphine stimulation was blocked by naloxone. Depending on its dose, morphine also increased or decreased the stimulating effect of dopamine on the dopamine-sensitive adenylate cyclase activity of caudate homogenate. Like dopamine, morphine'e effect on the adenylate cyclase activity was increased or decreased, respectively, by pretreating the animals with poly(I).poly(C) or with chloramphenicol. Thus, both dopamine and morphine appear to act on the same receptor. This \"new\" receptor differs from the one described by Snyder et al. and others, who demonstrated only binding affinity and no enzymatic activity. These data indicate that certain functions of the opiates might be mediated through the dopamine-sensitive adenylate cyclase of the caudate nuclei, which are the dopamine receptors in the brain."}
{"id": "PMID:206909", "title": "Identification of a polypeptide encoded by the avian sarcoma virus src gene.", "content": "Two techniques were used to search for the polypeptide encoded by the avian sarcoma virus (ASV) src gene. First, antiserum from rabbits bearing ASV-induced fibrosarcomas was used to immunoprecipitate a transformation-specific antigen from ASV-transformed chick embryo fibroblasts. This antigen has an apparent molecular weight (Mr) of 60,000. Second, the 3' one-third of the ASV genome, selected by oligo(dT)-cellulose chromatography and sucrose gradient sedimentation, was translated in a mRNA-dependent reticulocyte cell-free lysate. This RNA species programmed the synthesis of a polypeptide that comigrated with the transformation-specific antigen of Mr 60,000 immunoprecipitated from transformed cells. The methionine-containing tryptic peptides from the polypeptides of Mr 60,000 obtained from translation in vitro and from immunoprecipitation were found to be identical upon two-dimensional fractionation.", "contents": "Identification of a polypeptide encoded by the avian sarcoma virus src gene. Two techniques were used to search for the polypeptide encoded by the avian sarcoma virus (ASV) src gene. First, antiserum from rabbits bearing ASV-induced fibrosarcomas was used to immunoprecipitate a transformation-specific antigen from ASV-transformed chick embryo fibroblasts. This antigen has an apparent molecular weight (Mr) of 60,000. Second, the 3' one-third of the ASV genome, selected by oligo(dT)-cellulose chromatography and sucrose gradient sedimentation, was translated in a mRNA-dependent reticulocyte cell-free lysate. This RNA species programmed the synthesis of a polypeptide that comigrated with the transformation-specific antigen of Mr 60,000 immunoprecipitated from transformed cells. The methionine-containing tryptic peptides from the polypeptides of Mr 60,000 obtained from translation in vitro and from immunoprecipitation were found to be identical upon two-dimensional fractionation."}
{"id": "PMID:206910", "title": "Differential effects of perhydrohistrionicotoxin on neurally and iontophoretically evoked endplate currents.", "content": "Perhydrohistrionicotoxin, at concentrations of 10(-12)-10(-7) M, depressed the current generated by iontophoretic application of acetylcholine to endplate regions of soleus and extensor digitorum longus muscles of rats. However, no changes in the amplitude or time course of spontaneous miniature endplate potentials or currents were seen with these concentrations of toxin. Evoked endplate currents were also unaffected by the toxin. Similarly, the responses to iontophoretic acetylcholine were depressed by these concentrations of perhydrohistrionicotoxin in chronically denervated muscles. Depression of responses in both normal and chronically denervated muscles developed gradually, was greater at higher concentrations, and was reversible. The different effects of the toxin on neurally evoked currents and currents produced by iontophoretic application of acetylcholine raise the possibility of the existence of two different population of receptor complexes.", "contents": "Differential effects of perhydrohistrionicotoxin on neurally and iontophoretically evoked endplate currents. Perhydrohistrionicotoxin, at concentrations of 10(-12)-10(-7) M, depressed the current generated by iontophoretic application of acetylcholine to endplate regions of soleus and extensor digitorum longus muscles of rats. However, no changes in the amplitude or time course of spontaneous miniature endplate potentials or currents were seen with these concentrations of toxin. Evoked endplate currents were also unaffected by the toxin. Similarly, the responses to iontophoretic acetylcholine were depressed by these concentrations of perhydrohistrionicotoxin in chronically denervated muscles. Depression of responses in both normal and chronically denervated muscles developed gradually, was greater at higher concentrations, and was reversible. The different effects of the toxin on neurally evoked currents and currents produced by iontophoretic application of acetylcholine raise the possibility of the existence of two different population of receptor complexes."}
{"id": "PMID:206914", "title": "Suckling behavior of the infant rat: modulation by a developing neurotransmitter system.", "content": "Drugs which alter serotonin receptor activity modified the suckling behavior of 20-day-old rat pups. Suckling could be reinstated in nondeprived pups, which normally do not suckle, by blockade of serotonin receptors with methysergide. Stimulation  of serotonin receptors with quipazine inhibited suckling in deprived pups, and this effect was prevented by methysergide pretreatment. This evidence suggests that suckling in weaning age pups is controlled by a serotonergic inhibitory mechanism.", "contents": "Suckling behavior of the infant rat: modulation by a developing neurotransmitter system. Drugs which alter serotonin receptor activity modified the suckling behavior of 20-day-old rat pups. Suckling could be reinstated in nondeprived pups, which normally do not suckle, by blockade of serotonin receptors with methysergide. Stimulation  of serotonin receptors with quipazine inhibited suckling in deprived pups, and this effect was prevented by methysergide pretreatment. This evidence suggests that suckling in weaning age pups is controlled by a serotonergic inhibitory mechanism."}
{"id": "PMID:206917", "title": "New indolic cysticidal agents.", "content": "From a series of compounds having amino acid esters linked into the 3 position of substituted indole 3-acetic acids only the compounds 2 and 6 have shown promizing biological activity where as compound 2 process excystment property only, compound 6 has shown both excystment and cysticidal properties. All other compounds are inactive.", "contents": "New indolic cysticidal agents. From a series of compounds having amino acid esters linked into the 3 position of substituted indole 3-acetic acids only the compounds 2 and 6 have shown promizing biological activity where as compound 2 process excystment property only, compound 6 has shown both excystment and cysticidal properties. All other compounds are inactive."}
{"id": "PMID:206919", "title": "Detection of phase transitions and cooperative interactions by Avrami analysis of sigmoid biological time curves for muscle, nerve, growth, firefly, and infrared phosphorescence of green leaves, melanin, and cytochrome C.", "content": "A simple graphical analysis of sigmoid biological time curves for K+ leakage from muscle and nerve, for muscle tension and myosin ATPase, for animal, plant and bacterial growth, for firefly light flash, and for 3 micron infrared phosphorescence from green leaves, melanin, and cytochrome c shows good curve fits to the Avrami equation for phase transition kinetics. The  congruences imply that the analyzed processes are rate-limited by cooperative interactions and phase transitions. That implication is strengthened and its potential usefulness enhanced by the finding that the Avrami exponents of the above biological processes are not randomly distributed but cluster about certain values indicating (in the context of the Avrami theory) whether the spread of the new phase from nuclei within the old phase occurs in one, two, or three dimensions. The implication is further strengthened by the finding that similar types of biological processes show similar values of the Avrami exponent.", "contents": "Detection of phase transitions and cooperative interactions by Avrami analysis of sigmoid biological time curves for muscle, nerve, growth, firefly, and infrared phosphorescence of green leaves, melanin, and cytochrome C. A simple graphical analysis of sigmoid biological time curves for K+ leakage from muscle and nerve, for muscle tension and myosin ATPase, for animal, plant and bacterial growth, for firefly light flash, and for 3 micron infrared phosphorescence from green leaves, melanin, and cytochrome c shows good curve fits to the Avrami equation for phase transition kinetics. The  congruences imply that the analyzed processes are rate-limited by cooperative interactions and phase transitions. That implication is strengthened and its potential usefulness enhanced by the finding that the Avrami exponents of the above biological processes are not randomly distributed but cluster about certain values indicating (in the context of the Avrami theory) whether the spread of the new phase from nuclei within the old phase occurs in one, two, or three dimensions. The implication is further strengthened by the finding that similar types of biological processes show similar values of the Avrami exponent."}
{"id": "PMID:206921", "title": "Hyperlipidemia, atherosclerosis, and diabetes.", "content": "At present the two different mechanisms underlying the hypertriglyceridemia of diabetes are reasonably well defined. The rationale of therapy has grown from this knowledge. One form of hyperlipidemia is due to the hyperinsulinemia which results from the patient's resistance to insulin. The approach to treatment aims to overcome the insulin resistance. In most patients this is done by treating their obesity. The other form of hypertriglyceridemia results from insulin deficiency and is treated by bringing the patient's diabetes under control. There is strongly suggestive evidence that hypertriglyceridemia may be associated with a high risk of atherosclerosis. The reason for treating hypertriglyceridemia in general, and in the diabetic in particular, is to reduce this risk. However, it must be conceded that, at the moment, there is no information about the effect of lower triglyceride levels on the incidence of atherosclerosis. Hence much epidemiologic research is needed before our rationale for treatment can move from the realm of hope to the realm of definite proof. In the mean time an attack on this and the other risk factors is the best way we have to attempt to prevent the major complication of diabetes, atherosclerosis.", "contents": "Hyperlipidemia, atherosclerosis, and diabetes. At present the two different mechanisms underlying the hypertriglyceridemia of diabetes are reasonably well defined. The rationale of therapy has grown from this knowledge. One form of hyperlipidemia is due to the hyperinsulinemia which results from the patient's resistance to insulin. The approach to treatment aims to overcome the insulin resistance. In most patients this is done by treating their obesity. The other form of hypertriglyceridemia results from insulin deficiency and is treated by bringing the patient's diabetes under control. There is strongly suggestive evidence that hypertriglyceridemia may be associated with a high risk of atherosclerosis. The reason for treating hypertriglyceridemia in general, and in the diabetic in particular, is to reduce this risk. However, it must be conceded that, at the moment, there is no information about the effect of lower triglyceride levels on the incidence of atherosclerosis. Hence much epidemiologic research is needed before our rationale for treatment can move from the realm of hope to the realm of definite proof. In the mean time an attack on this and the other risk factors is the best way we have to attempt to prevent the major complication of diabetes, atherosclerosis."}
{"id": "PMID:206922", "title": "Experimental and clinical evidence of the antidepressant effect of a beta-adrenergic stimulant.", "content": "A group of 49 patients with depressive illness were treated in an uncontrolled study by the intravenous administration of the beta-adrenergic stimulant, salbutamol. The results suggested a rapid antidepressant action in the majority of cases without significant adverse effects.", "contents": "Experimental and clinical evidence of the antidepressant effect of a beta-adrenergic stimulant. A group of 49 patients with depressive illness were treated in an uncontrolled study by the intravenous administration of the beta-adrenergic stimulant, salbutamol. The results suggested a rapid antidepressant action in the majority of cases without significant adverse effects."}
{"id": "PMID:206923", "title": "Model insomnia, noise, and methylphenidate, used for the evaluation of hypnotic drugs.", "content": "Experimental sleep disturbance (model insomnia) was produced by intermittent white noise and the administration of 10 mg of methylphenidate (MPD). The effects of flurazepam (FZP) 15 mg and triazolam (TZM) 0.25 mg on these models was investigated. All night sleep polygraphy was performed on 8 normal male subjects under each of the following 9 conditions: baseline, TZM 0.25 mg, FZP 15 mg, white noise alone, noise and TZM, noise and FZP, MPD alone, MPD and TZM, and MPD and FZP. A reduction in total sleep time and stage were (S-REM) and an increase in the wakening stage were observed with both noise and MPD. Stage 4 sleep was reduced only by MPD. Administration of TZM or EZP did not cause any significant change in sleep parameters. These drugs in combination with noise or MPD resulted in almost complete recovery of the sleep disturbance induced by noise or MPD, except for a reduction in S-REM. These results indicate that model insomnia, particularly MPD insomnia, will assist in the evaluation of hypnotic drugs.", "contents": "Model insomnia, noise, and methylphenidate, used for the evaluation of hypnotic drugs. Experimental sleep disturbance (model insomnia) was produced by intermittent white noise and the administration of 10 mg of methylphenidate (MPD). The effects of flurazepam (FZP) 15 mg and triazolam (TZM) 0.25 mg on these models was investigated. All night sleep polygraphy was performed on 8 normal male subjects under each of the following 9 conditions: baseline, TZM 0.25 mg, FZP 15 mg, white noise alone, noise and TZM, noise and FZP, MPD alone, MPD and TZM, and MPD and FZP. A reduction in total sleep time and stage were (S-REM) and an increase in the wakening stage were observed with both noise and MPD. Stage 4 sleep was reduced only by MPD. Administration of TZM or EZP did not cause any significant change in sleep parameters. These drugs in combination with noise or MPD resulted in almost complete recovery of the sleep disturbance induced by noise or MPD, except for a reduction in S-REM. These results indicate that model insomnia, particularly MPD insomnia, will assist in the evaluation of hypnotic drugs."}
{"id": "PMID:206932", "title": "Changes in leucocyte cytochrome oxidase activity associated with deficiency of copper in laboratory and farm animals.", "content": "The cytochrome oxidase activity of circulating leucocytes was investigated by means of a semiquantitative method using blood films. A significant decrease in activity was found in male rats, cattle and sheep that had been deprived of copper. During copper depletion, leucocyte cytochrome oxidase activity declined more slowly than did plasma copper concentration and plasma ferroxidase I activity, and so was less sensitive as a guide to the copper status of the animal.", "contents": "Changes in leucocyte cytochrome oxidase activity associated with deficiency of copper in laboratory and farm animals. The cytochrome oxidase activity of circulating leucocytes was investigated by means of a semiquantitative method using blood films. A significant decrease in activity was found in male rats, cattle and sheep that had been deprived of copper. During copper depletion, leucocyte cytochrome oxidase activity declined more slowly than did plasma copper concentration and plasma ferroxidase I activity, and so was less sensitive as a guide to the copper status of the animal."}
{"id": "PMID:206934", "title": "Characteristics of inapparent Aleutian disease virus infection in mink.", "content": "Inapparent of nonprogressive Aleutian disease virus (ADV) infection is a subclinical but persistent virus infection of mink. Mink with the inapparent type of ADV infection when subjected to stress did not develop the progessive form of the disease. However, when challenged with a large dose of the virus, these mink did develop progressive Aleutian disease indicating that they were not highly resistant to the virus. Sera of mink with either the progressive of the inapparent type of ADV infection did not neutralise the virus. The anti-ADV antibody activity in mink with inapparent type of ADV infection was in the IgG fraction of the serum the same as in mink with progressive Aleutian disease. These data indicate that the resistance of the mink with inapparent infection as compared to mink with progressive Aleutian disease was not due to a difference in the class of immunoglobulin response to the virus. However, mink with progressive Aleutian disease showed a greatly increased immunoglobulin response.", "contents": "Characteristics of inapparent Aleutian disease virus infection in mink. Inapparent of nonprogressive Aleutian disease virus (ADV) infection is a subclinical but persistent virus infection of mink. Mink with the inapparent type of ADV infection when subjected to stress did not develop the progessive form of the disease. However, when challenged with a large dose of the virus, these mink did develop progressive Aleutian disease indicating that they were not highly resistant to the virus. Sera of mink with either the progressive of the inapparent type of ADV infection did not neutralise the virus. The anti-ADV antibody activity in mink with inapparent type of ADV infection was in the IgG fraction of the serum the same as in mink with progressive Aleutian disease. These data indicate that the resistance of the mink with inapparent infection as compared to mink with progressive Aleutian disease was not due to a difference in the class of immunoglobulin response to the virus. However, mink with progressive Aleutian disease showed a greatly increased immunoglobulin response."}
{"id": "PMID:206935", "title": "An inactivated parainfluenza virus type 3 vaccine: the influence of vaccination regime on the response of calves and their subsequent resistance to challenge.", "content": "Calves maintained in insolated pens were vaccinated with an inactivated parainfluenza virus type (3) (pi3) vaccine usingparenteral and local route singly and in combination. The calves were subsequently monitored for serum antibody response and challenged intranasally with live virus to assess the protection derived from vaccination. Calves receiving one subcutaneous dose of vaccine in oil adjuvant produced a marked antibody response and were partially protected against challenge. Those receiving two successive subcutaneous doses produced a much greater antiboyd response and were completely protected against challenge. One intranasal dose of aqueous vaccine failed elicit a significant serum antibody response or protection against challenge. However, there was some evidence that intranasal vaccination following a single subcutaneous vaccination produced more effective immunity than one subcutaneous dose alone. Thus a vaccination regime was established which protected calves against experimental challenge and which could thefore be used in the field to assess the role of Pi3 virus in calf respiratory disease.", "contents": "An inactivated parainfluenza virus type 3 vaccine: the influence of vaccination regime on the response of calves and their subsequent resistance to challenge. Calves maintained in insolated pens were vaccinated with an inactivated parainfluenza virus type (3) (pi3) vaccine usingparenteral and local route singly and in combination. The calves were subsequently monitored for serum antibody response and challenged intranasally with live virus to assess the protection derived from vaccination. Calves receiving one subcutaneous dose of vaccine in oil adjuvant produced a marked antibody response and were partially protected against challenge. Those receiving two successive subcutaneous doses produced a much greater antiboyd response and were completely protected against challenge. One intranasal dose of aqueous vaccine failed elicit a significant serum antibody response or protection against challenge. However, there was some evidence that intranasal vaccination following a single subcutaneous vaccination produced more effective immunity than one subcutaneous dose alone. Thus a vaccination regime was established which protected calves against experimental challenge and which could thefore be used in the field to assess the role of Pi3 virus in calf respiratory disease."}
{"id": "PMID:206939", "title": "[Conditions of inactivation of viruses in water with chlorination].", "content": "Spread within the environment, especially in water, of enteral pathogens has stimulated the greatest interest and raised many problems that have not yet been fully elucidated. Of particular importance is the possibility of inactivating enteroviruses by chlorinating water. The antiviral disinfection of water by chlorination has proved efficient under the conditions mentioned, lowering the incidence of water-borne viral diseases.", "contents": "[Conditions of inactivation of viruses in water with chlorination]. Spread within the environment, especially in water, of enteral pathogens has stimulated the greatest interest and raised many problems that have not yet been fully elucidated. Of particular importance is the possibility of inactivating enteroviruses by chlorinating water. The antiviral disinfection of water by chlorination has proved efficient under the conditions mentioned, lowering the incidence of water-borne viral diseases."}
{"id": "PMID:206940", "title": "[Asthma and tuberculosis (considerations based on hospital case studies)].", "content": "The relationship between bronchic asthma and tuberculosis has stimulated the greatest interest and most controversy. The present paper refers to 55 cases, i.e. 29 males  (52%) and 26 females (48%). Most of the men were over 50 and the women over the age of 40 years. In 50 cases (90%) bronchial asthma developed 6 to 25 years after the tb lesions had become stable. Only 5 cases (10%) presented bronchial asthma with evolutive pulmonary tb. Although tuberculin hyperergy was encountered in 26 cases (47%) in none of the cases could a diagnosis of tuberculin asthma be established. In the group studied, the patients' age, the clinical and evolutive aspect of the bronchial asthma lists in the group of late asthmas. Against the background of the postuberculosis syndrome, the evolution of asthma is as a rule severe. Similarly, asthma accompanied by evolutive pulmonary tb, is in general very severe, hypersecretory and suprainfected with common germs.", "contents": "[Asthma and tuberculosis (considerations based on hospital case studies)]. The relationship between bronchic asthma and tuberculosis has stimulated the greatest interest and most controversy. The present paper refers to 55 cases, i.e. 29 males  (52%) and 26 females (48%). Most of the men were over 50 and the women over the age of 40 years. In 50 cases (90%) bronchial asthma developed 6 to 25 years after the tb lesions had become stable. Only 5 cases (10%) presented bronchial asthma with evolutive pulmonary tb. Although tuberculin hyperergy was encountered in 26 cases (47%) in none of the cases could a diagnosis of tuberculin asthma be established. In the group studied, the patients' age, the clinical and evolutive aspect of the bronchial asthma lists in the group of late asthmas. Against the background of the postuberculosis syndrome, the evolution of asthma is as a rule severe. Similarly, asthma accompanied by evolutive pulmonary tb, is in general very severe, hypersecretory and suprainfected with common germs."}
{"id": "PMID:206941", "title": "[Studies of pulmonary function in the post-virosis period].", "content": "The pulmonary function was studied in 21 patients with viral diseases of the lungs 10 to 18 days after the acute episode. In 14 cases all the parameters tested were normal; in 7 cases the alterations found led to a diagnosis of obstructive syndrome of the smaller airways (increased intrapulmonary helium mixture time, increased expired CO2 alveolar slope and residual volume). The alterations were again found on repeating the tests after 6--10 months. The various mechanisms that might cause obstruction are discussed (persistent inflammation, increased tonus of the bronchiolar musculature, hypersecretion in the smaller airways, alteration of the surfactant). In conclusion the authors raise the question of whether the obstructive alterations following pulmonary viral diseases might not be one of the etiopathogenic factors of chronic, obstructive bronchopneumopathy.", "contents": "[Studies of pulmonary function in the post-virosis period]. The pulmonary function was studied in 21 patients with viral diseases of the lungs 10 to 18 days after the acute episode. In 14 cases all the parameters tested were normal; in 7 cases the alterations found led to a diagnosis of obstructive syndrome of the smaller airways (increased intrapulmonary helium mixture time, increased expired CO2 alveolar slope and residual volume). The alterations were again found on repeating the tests after 6--10 months. The various mechanisms that might cause obstruction are discussed (persistent inflammation, increased tonus of the bronchiolar musculature, hypersecretion in the smaller airways, alteration of the surfactant). In conclusion the authors raise the question of whether the obstructive alterations following pulmonary viral diseases might not be one of the etiopathogenic factors of chronic, obstructive bronchopneumopathy."}
{"id": "PMID:206942", "title": "[Immediate and late results of the use of \"3 + 6\" regimens in the routine treatment of pulmonary tuberculosis].", "content": "An assessment is carried out of the results obtained in the Constantza County after over 2 years of application of the \"3 + 6\" regimens (INH + RMP and INH + SM + EMB) in a group of 119 patients with initially bacteriologically confirmed pulmonary tuberculosis. The standard regimens applied were not replaced with other regimens. The dynamics of negativation in cultures confirmed that over 50% of the patients had become negative after the first month of treatment. For practical purposes negativation was completed before 3 months in all the cases. The only two failures were recorded in the first three months after the treatment was ended. No re-positivation was noted in the second year of the follow-up. A stable resolution was achieved in 98% of the patients.", "contents": "[Immediate and late results of the use of \"3 + 6\" regimens in the routine treatment of pulmonary tuberculosis]. An assessment is carried out of the results obtained in the Constantza County after over 2 years of application of the \"3 + 6\" regimens (INH + RMP and INH + SM + EMB) in a group of 119 patients with initially bacteriologically confirmed pulmonary tuberculosis. The standard regimens applied were not replaced with other regimens. The dynamics of negativation in cultures confirmed that over 50% of the patients had become negative after the first month of treatment. For practical purposes negativation was completed before 3 months in all the cases. The only two failures were recorded in the first three months after the treatment was ended. No re-positivation was noted in the second year of the follow-up. A stable resolution was achieved in 98% of the patients."}
{"id": "PMID:206944", "title": "[The effectiveness of some culture media with pyruvic acid bases for the isolation of mycobacteria from sputum].", "content": "The authors have studied the value of culture media based on pyruvic acid (the Dixon medium and an original medium called P.T.) in the isolation of mycobacteria from sputum, as compared with the L\u00f6wenstein-Jensen medium. The studies were carried out in two groups of patients: 1043 samples were collected from ambulatory patients and 1740 samples were collected from hospitalized patients. The superiority of the Dixon and of the P.T. media was confirmed by the increased percentage of positive cultures (11% and 20% respectively) as compared with the L\u00f6wenstein-Jensen medium. With these media it was possible to isolate mycobacteria 7--14 days earlier than with the other media. On the basis of the results obtained the authors recommend the use, in parallel, especially in those cases when the samples contain only a small number of bacteria, of the L\u00f6wenstein-Jensen medium and one of the media based on pyruvic acid.", "contents": "[The effectiveness of some culture media with pyruvic acid bases for the isolation of mycobacteria from sputum]. The authors have studied the value of culture media based on pyruvic acid (the Dixon medium and an original medium called P.T.) in the isolation of mycobacteria from sputum, as compared with the L\u00f6wenstein-Jensen medium. The studies were carried out in two groups of patients: 1043 samples were collected from ambulatory patients and 1740 samples were collected from hospitalized patients. The superiority of the Dixon and of the P.T. media was confirmed by the increased percentage of positive cultures (11% and 20% respectively) as compared with the L\u00f6wenstein-Jensen medium. With these media it was possible to isolate mycobacteria 7--14 days earlier than with the other media. On the basis of the results obtained the authors recommend the use, in parallel, especially in those cases when the samples contain only a small number of bacteria, of the L\u00f6wenstein-Jensen medium and one of the media based on pyruvic acid."}
{"id": "PMID:206945", "title": "[Dynamics of temporary work incapacity and disability caused by tuberculosis in the Bra\u015fov district in the 1971-1976 period].", "content": "The paper stresses the fact that a decrease by approximately 50% was obtained, of the severity index due to tuberculosis, and by 63,6% of the incidence of invalidity through tuberculosis as a result of decreased morbidity and of the application of more efficient therapies over a shorter period of time. The prevalence of invalidity through tuberculosis recorded but a slight decrease since those subjects who had sequellae involving irrecoverable cardiorespiratory insufficiency were maintained in this category.", "contents": "[Dynamics of temporary work incapacity and disability caused by tuberculosis in the Bra\u015fov district in the 1971-1976 period]. The paper stresses the fact that a decrease by approximately 50% was obtained, of the severity index due to tuberculosis, and by 63,6% of the incidence of invalidity through tuberculosis as a result of decreased morbidity and of the application of more efficient therapies over a shorter period of time. The prevalence of invalidity through tuberculosis recorded but a slight decrease since those subjects who had sequellae involving irrecoverable cardiorespiratory insufficiency were maintained in this category."}
{"id": "PMID:206946", "title": "[Risk factors in infection and development of tuberculosis in students].", "content": "A study was carried out in 266 571 students, examined during the 1952--1974 interval, on a series of risk factors of infection and morbidity from tuberculosis with regard to certain epidemiological, immunobiologic and peristasis parameters. In the interval studied, morbidity from tuberculosis fell sharply from 923 per 100,000 in 1952 to 83 per 100,000 in 1974. The highest proportion of infection occured in the first three years at the university, particularly among meidcal students. The risk of infection of alergic subjects with an intradermoreaction greater than 15 mm in diameter, was approximately twice that the hypo- or normoergic subjects and the proportion of vaccinates who contracted the disease three times smaller than that of the non-vaccinated subjects.", "contents": "[Risk factors in infection and development of tuberculosis in students]. A study was carried out in 266 571 students, examined during the 1952--1974 interval, on a series of risk factors of infection and morbidity from tuberculosis with regard to certain epidemiological, immunobiologic and peristasis parameters. In the interval studied, morbidity from tuberculosis fell sharply from 923 per 100,000 in 1952 to 83 per 100,000 in 1974. The highest proportion of infection occured in the first three years at the university, particularly among meidcal students. The risk of infection of alergic subjects with an intradermoreaction greater than 15 mm in diameter, was approximately twice that the hypo- or normoergic subjects and the proportion of vaccinates who contracted the disease three times smaller than that of the non-vaccinated subjects."}
{"id": "PMID:206956", "title": "[Calification of the dental system in dialized patients].", "content": "The authors present the case of an eight-years-old child, dialysed since the age of two following a bilateral nephrectomy. The chronological appearance of the teeth was not disturbed. By contrast, there was a delay in mineralisation of the dental organ, and in particular the root. There was lysis of the alveolar bone, resulting in a parodontopathy. The authors distinguish two ages in the effects of dialysis: the first period is that of the construction of the dental system and the second is the adult age at which the dental system is constituted.", "contents": "[Calification of the dental system in dialized patients]. The authors present the case of an eight-years-old child, dialysed since the age of two following a bilateral nephrectomy. The chronological appearance of the teeth was not disturbed. By contrast, there was a delay in mineralisation of the dental organ, and in particular the root. There was lysis of the alveolar bone, resulting in a parodontopathy. The authors distinguish two ages in the effects of dialysis: the first period is that of the construction of the dental system and the second is the adult age at which the dental system is constituted."}
{"id": "PMID:206957", "title": "Effect of inorganic ions and surface active organic compounds on the adherence of oral streptococci.", "content": "A reduction in the adherence of oral streptococci was observed after topical application of aluminum ions to standardized dentin test pieces whereas pyrophosphate and tripolyphosphate seemed to inhibit the adherence after incorporation in the incubation solution. A pronounced effect was recorded after topical application of surfactants with the positively charged primary amino group as end group. Hydrofluorides of several such aliphatic amines effectively reduced the number of colony-forming units washed off from the test pieces. Also the free base of hexadecylamine showed a similar effect. Inhibition of adherence was also obtained with long chain esters of lysine, with an optimum at 16 carbon atoms in the alcohol group. These compounds have the advantage of being built up from molecules known to the body.", "contents": "Effect of inorganic ions and surface active organic compounds on the adherence of oral streptococci. A reduction in the adherence of oral streptococci was observed after topical application of aluminum ions to standardized dentin test pieces whereas pyrophosphate and tripolyphosphate seemed to inhibit the adherence after incorporation in the incubation solution. A pronounced effect was recorded after topical application of surfactants with the positively charged primary amino group as end group. Hydrofluorides of several such aliphatic amines effectively reduced the number of colony-forming units washed off from the test pieces. Also the free base of hexadecylamine showed a similar effect. Inhibition of adherence was also obtained with long chain esters of lysine, with an optimum at 16 carbon atoms in the alcohol group. These compounds have the advantage of being built up from molecules known to the body."}
{"id": "PMID:206958", "title": "Hereditary gingival hyperplasia and physical maturation.", "content": "In a family with eight children, six of the children suffered from gingival hyperplasia. Dental age was determined for five of the affected children. In four it was retarded in relation to chronologic age, but within normal limits. The skeletal age of the same five children was retarded by more than 2 standard deviations. The heights of three of these five children were clearly below the 2.5th percentile height curve. The two most retarded children were examined by pediatricians. No hematologic changes or evidence of malabsorption from the alimentary tract could be found. It is suggested that in this family retardation of physical development may be linked with gingival hyperplasia.", "contents": "Hereditary gingival hyperplasia and physical maturation. In a family with eight children, six of the children suffered from gingival hyperplasia. Dental age was determined for five of the affected children. In four it was retarded in relation to chronologic age, but within normal limits. The skeletal age of the same five children was retarded by more than 2 standard deviations. The heights of three of these five children were clearly below the 2.5th percentile height curve. The two most retarded children were examined by pediatricians. No hematologic changes or evidence of malabsorption from the alimentary tract could be found. It is suggested that in this family retardation of physical development may be linked with gingival hyperplasia."}
{"id": "PMID:206960", "title": "[The treatment of chronic pain with psychotropic drugs].", "content": "The results of long experience with psychotropic drugs in the treatment of chronic and severe pain resistant to ordinary therapy are reported. In 103 in-patients with chronic and severe pain caused by neurological conditions and treated with a combination of thymoleptics and neuroleptics, 82% showed a marked improvement. These encouraging results are compared with the results of other studies published in this field. The pharmacological basis of this good action is briefly discussed, together with the advantages of the use of psychotropic drugs and especially the combination of thymoleptics and neuroleptics. A clearcut dosage schedule for in- and out-patients using imipramine (Tofranil) or chlorimipramine (Anafranil) and haloperidol (Haldol) is established.", "contents": "[The treatment of chronic pain with psychotropic drugs]. The results of long experience with psychotropic drugs in the treatment of chronic and severe pain resistant to ordinary therapy are reported. In 103 in-patients with chronic and severe pain caused by neurological conditions and treated with a combination of thymoleptics and neuroleptics, 82% showed a marked improvement. These encouraging results are compared with the results of other studies published in this field. The pharmacological basis of this good action is briefly discussed, together with the advantages of the use of psychotropic drugs and especially the combination of thymoleptics and neuroleptics. A clearcut dosage schedule for in- and out-patients using imipramine (Tofranil) or chlorimipramine (Anafranil) and haloperidol (Haldol) is established."}
{"id": "PMID:206963", "title": "The essentiality of vitamin D metabolites for embryonic chick development.", "content": "Laying hens maintained on 1,25-dihydroxyvitamin D3 as their sole source of vitamin D produce eggs which appear normal but which produce embryos having a defective upper mandible and which die at 18 to 19 days of embryonic life. Hens maintained on 25-hydroxyvitamin D3, on the other hand, produce normal embryos. Hens fed a vitamin D deficient diet produce eggs which develop the same embryonic defect. Injection of the affected eggs from the 1,25-dihydroxyvitamin D3 fed hens with vitamin D3, 25-hydroxyvitamin D3, or 1,25-dihydroxyvitamin D3 greatly increases the percentage of normal embryos. It therefore appears that 1,25-dihydroxyvitamin D3 is not transferred from hen to egg in sufficient amounts to support embryonic development and that vitamin D or its metabolites, or both, are necessary for normal chick embryo development.", "contents": "The essentiality of vitamin D metabolites for embryonic chick development. Laying hens maintained on 1,25-dihydroxyvitamin D3 as their sole source of vitamin D produce eggs which appear normal but which produce embryos having a defective upper mandible and which die at 18 to 19 days of embryonic life. Hens maintained on 25-hydroxyvitamin D3, on the other hand, produce normal embryos. Hens fed a vitamin D deficient diet produce eggs which develop the same embryonic defect. Injection of the affected eggs from the 1,25-dihydroxyvitamin D3 fed hens with vitamin D3, 25-hydroxyvitamin D3, or 1,25-dihydroxyvitamin D3 greatly increases the percentage of normal embryos. It therefore appears that 1,25-dihydroxyvitamin D3 is not transferred from hen to egg in sufficient amounts to support embryonic development and that vitamin D or its metabolites, or both, are necessary for normal chick embryo development."}
{"id": "PMID:206964", "title": "Synaptic potentials in sympathetic ganglia: are they mediated by cyclic nucleotides?", "content": "The hypothesis that cyclic nucleotides are intracellular second messengers mediating the generation of synaptic potentials was studied in the sympathetic ganglia of the bullfrog. Synaptic potentials and the effect of administering cyclic nucleotides and agents which affect cyclic nucleotide metabolism were recorded by the sucrose gap technique. The administration of adenosine 3',5'-monophosphate (cyclic AMP), guanosine 3',5'-monophosphate (cyclic GMP), or several of their derivatives produced little or no change in membrane potential. Prostaglandin E1 did not block the generation of postsynaptic potentials. Theophylline produced membrane effects that were different from those associated with postsynaptic potential generation; it also reduced the slow excitatory postsynaptic potential (EPSP) and potentiated the slow inhibitory postsynaptic potential (IPSP). The administration of papaverine, however, reduced both the slow EPSP and the slow IPSP. Although synaptic stimulation increases both cyclic GMP and cyclic AMP in these neurons, these results raise the possibility that these cyclic nucleotides may have functionla roles other than mediation of synaptic potentials.", "contents": "Synaptic potentials in sympathetic ganglia: are they mediated by cyclic nucleotides? The hypothesis that cyclic nucleotides are intracellular second messengers mediating the generation of synaptic potentials was studied in the sympathetic ganglia of the bullfrog. Synaptic potentials and the effect of administering cyclic nucleotides and agents which affect cyclic nucleotide metabolism were recorded by the sucrose gap technique. The administration of adenosine 3',5'-monophosphate (cyclic AMP), guanosine 3',5'-monophosphate (cyclic GMP), or several of their derivatives produced little or no change in membrane potential. Prostaglandin E1 did not block the generation of postsynaptic potentials. Theophylline produced membrane effects that were different from those associated with postsynaptic potential generation; it also reduced the slow excitatory postsynaptic potential (EPSP) and potentiated the slow inhibitory postsynaptic potential (IPSP). The administration of papaverine, however, reduced both the slow EPSP and the slow IPSP. Although synaptic stimulation increases both cyclic GMP and cyclic AMP in these neurons, these results raise the possibility that these cyclic nucleotides may have functionla roles other than mediation of synaptic potentials."}
{"id": "PMID:206965", "title": "Absence of adenosine deaminase activity in a mammalian cell line transformed by Rous sarcoma virus.", "content": "No detectable adenosine deaminase activity was found in whole cells or 105,000g cytosol preparations of B-mix K-44/6 cells when either [3H]adenosine or [3H]arabinosyladenine was used as substrate. When grown in tissue culture medium supplemented with horse serum these cells provide a deaminase-free system not requiring the use of an adenosine deaminase inhibitor.", "contents": "Absence of adenosine deaminase activity in a mammalian cell line transformed by Rous sarcoma virus. No detectable adenosine deaminase activity was found in whole cells or 105,000g cytosol preparations of B-mix K-44/6 cells when either [3H]adenosine or [3H]arabinosyladenine was used as substrate. When grown in tissue culture medium supplemented with horse serum these cells provide a deaminase-free system not requiring the use of an adenosine deaminase inhibitor."}
{"id": "PMID:206962", "title": "Establishment of an epitheloid cell line and a fusiform cell line from a patient with nasopharyngeal carcinoma.", "content": "An epithelioid cell line and a fusiform cell line were established from a tumor biopsy from a patient with nasopharyngeal carcinoma which as histologically diagnosed as a well differentiated squamous cell carcinoma. Based on studies of the cell growth pattern, chromosome analysis, heterotransplantation, and electron microscopy, these two cell lines were considered to be squamous carcinoma cells, and the fusiform cells might have originated from the epithelioid cells. There were many round cells on top of the epithelioid and fusiform cell sheets, many of which became continuously detached into the medium. Cultures initiated from these floating round cells grew into their original epithelioid or fusiform forms. No lymphoblastoid cell line could be established after cultivating these two cell lines for more than one year. No EB virus particle or early antigen could be detected in these two cell lines by means of electron microscopic examination and indirect immunofluorescence test.", "contents": "Establishment of an epitheloid cell line and a fusiform cell line from a patient with nasopharyngeal carcinoma. An epithelioid cell line and a fusiform cell line were established from a tumor biopsy from a patient with nasopharyngeal carcinoma which as histologically diagnosed as a well differentiated squamous cell carcinoma. Based on studies of the cell growth pattern, chromosome analysis, heterotransplantation, and electron microscopy, these two cell lines were considered to be squamous carcinoma cells, and the fusiform cells might have originated from the epithelioid cells. There were many round cells on top of the epithelioid and fusiform cell sheets, many of which became continuously detached into the medium. Cultures initiated from these floating round cells grew into their original epithelioid or fusiform forms. No lymphoblastoid cell line could be established after cultivating these two cell lines for more than one year. No EB virus particle or early antigen could be detected in these two cell lines by means of electron microscopic examination and indirect immunofluorescence test."}
{"id": "PMID:206966", "title": "Reversed-phase, high-pressure liquid chromatography of peptides and proteins with ion-pairing reagents.", "content": "Reversed-phase, high-pressure liquid chromatography has been successfully applied to the analysis of peptides and proteins by the addition of hydrophilic (for example, phosphoric acid) or hydrophobic (for example, hexanesulfonic acid) ion-pairing reagents, or both, to the mobile phase. Examples described included proteins such as insulin, glucagon, and 1-24 ACTH pentaacetate (ACTH is adrenocorticotrophic hormone).", "contents": "Reversed-phase, high-pressure liquid chromatography of peptides and proteins with ion-pairing reagents. Reversed-phase, high-pressure liquid chromatography has been successfully applied to the analysis of peptides and proteins by the addition of hydrophilic (for example, phosphoric acid) or hydrophobic (for example, hexanesulfonic acid) ion-pairing reagents, or both, to the mobile phase. Examples described included proteins such as insulin, glucagon, and 1-24 ACTH pentaacetate (ACTH is adrenocorticotrophic hormone)."}
{"id": "PMID:206967", "title": "Adrenocorticotropin in rat brain: immunocytochemical localization in cells and axons.", "content": "By means of antiserum (purified by affinity chromatography) directed against adrenocorticotropin (ACTH) 11-24, cell bodies and beaded axons were visualized in rat brain. The ACTH-like immunoreactivity (ACTH-LI) was primarily located in the hypothalamus (cells and axons). Fibers were scattered throughout thalamus, amygdala, periaqueductal gray area, and reticular formation. There was no change in the distribution of ACTH-LI in rats that had been subjected to hypophysectomy. This distribution of ACTH-LI parallels that of beta-lipotropin and is altered by specific lesions in a similar fashion. The presence of ACTH-LI in cells and beaded axons in brain raises the possibility that it is a neuroregulator functioning as a neurotransmitter, neuromodulator, or neurohormone.", "contents": "Adrenocorticotropin in rat brain: immunocytochemical localization in cells and axons. By means of antiserum (purified by affinity chromatography) directed against adrenocorticotropin (ACTH) 11-24, cell bodies and beaded axons were visualized in rat brain. The ACTH-like immunoreactivity (ACTH-LI) was primarily located in the hypothalamus (cells and axons). Fibers were scattered throughout thalamus, amygdala, periaqueductal gray area, and reticular formation. There was no change in the distribution of ACTH-LI in rats that had been subjected to hypophysectomy. This distribution of ACTH-LI parallels that of beta-lipotropin and is altered by specific lesions in a similar fashion. The presence of ACTH-LI in cells and beaded axons in brain raises the possibility that it is a neuroregulator functioning as a neurotransmitter, neuromodulator, or neurohormone."}
{"id": "PMID:206968", "title": "[Cerebral tomodensitometry (scanner) and accident sequelae: its medico-legal value].", "content": "The authors report their experience of one years use of a cerebral scanner in the investigation of the sequelae of head injuries, and the medico-legal interest of this discovery. It permits one to visualise the pathological processes responsible for the symptoms following head injuries and its is thus of major intetrest in legal medicine where the subjective factor in these symptoms is difficult to assess. Increasing considerably the proportion of definite etiologies in this pathology, the authors believe that this new method will become standard in the medico-legal assessment of head injuries.", "contents": "[Cerebral tomodensitometry (scanner) and accident sequelae: its medico-legal value]. The authors report their experience of one years use of a cerebral scanner in the investigation of the sequelae of head injuries, and the medico-legal interest of this discovery. It permits one to visualise the pathological processes responsible for the symptoms following head injuries and its is thus of major intetrest in legal medicine where the subjective factor in these symptoms is difficult to assess. Increasing considerably the proportion of definite etiologies in this pathology, the authors believe that this new method will become standard in the medico-legal assessment of head injuries."}
{"id": "PMID:206969", "title": "[Temporal arteritis and rhizomelic pseudo-polyarthritis. Clinical aspects and nosologic problems. Apropos of 48 cases].", "content": "The authors report 40 cases of temporal arteritis, of which 16 were associated with pseudo-polyarthritis, and 8 cases of polyarthritis alone. The clinical picture of temporal arteritis in the elderly, includes headaches in 95% of cases, clinical changes in the superficial head arteries in 75% of cases, joint and muscle signs dominated by pseudo-polyarthritis in 40% of cases; general signs were practically constant. A major inflammatory syndrome was also constant. From the histological point of view, there was pan-arteritis with giant cells, and their wide diffusion is shown by the presence of eye signs in 27.5% of cases, brain signs in 10% of cases, and extra-cephalic vascular signs in 10%. The relationship in classification between temporal arteritis and polyarthritis of the roots of the limbs is recalled. The course is long, the duration of corticosteroid therapy should never be less than two years; relapses are common but the mortality appears low.", "contents": "[Temporal arteritis and rhizomelic pseudo-polyarthritis. Clinical aspects and nosologic problems. Apropos of 48 cases]. The authors report 40 cases of temporal arteritis, of which 16 were associated with pseudo-polyarthritis, and 8 cases of polyarthritis alone. The clinical picture of temporal arteritis in the elderly, includes headaches in 95% of cases, clinical changes in the superficial head arteries in 75% of cases, joint and muscle signs dominated by pseudo-polyarthritis in 40% of cases; general signs were practically constant. A major inflammatory syndrome was also constant. From the histological point of view, there was pan-arteritis with giant cells, and their wide diffusion is shown by the presence of eye signs in 27.5% of cases, brain signs in 10% of cases, and extra-cephalic vascular signs in 10%. The relationship in classification between temporal arteritis and polyarthritis of the roots of the limbs is recalled. The course is long, the duration of corticosteroid therapy should never be less than two years; relapses are common but the mortality appears low."}
{"id": "PMID:206970", "title": "[Surgical treatment of primary hyperlipoproteinemia].", "content": "The authors report 4 cases of hyperlipemia and show the great benefit which results from ileal exclusion when there is an atherogenic risk. The considerable reduction in total lipid, cholesterol, triglycerides, and prebeta-lipoproteins is constant together with clarification of the serum. In one case, angina pectoris regressed considerably, as did arteritis of the lower limbs (unlimited walking became possible, oscillometry in the leg improved from 2 to 7). Surgery is indicated whenever by lack of will power, the diet and medical treatment cannot be followed, when social and economic conditions make proper medical treatment impossible, or when the latter has failed. The existence of arterial lesions, cardiac or cerebral complications makes surgery even more urgent. Gall-stones were observed in gall bladder. The authors raise the problem of oxalate stones. Only type II familial hyperlipemia in homozygotes should be excluded: and end-to-side portacaval anastomosis seems to be preferable.", "contents": "[Surgical treatment of primary hyperlipoproteinemia]. The authors report 4 cases of hyperlipemia and show the great benefit which results from ileal exclusion when there is an atherogenic risk. The considerable reduction in total lipid, cholesterol, triglycerides, and prebeta-lipoproteins is constant together with clarification of the serum. In one case, angina pectoris regressed considerably, as did arteritis of the lower limbs (unlimited walking became possible, oscillometry in the leg improved from 2 to 7). Surgery is indicated whenever by lack of will power, the diet and medical treatment cannot be followed, when social and economic conditions make proper medical treatment impossible, or when the latter has failed. The existence of arterial lesions, cardiac or cerebral complications makes surgery even more urgent. Gall-stones were observed in gall bladder. The authors raise the problem of oxalate stones. Only type II familial hyperlipemia in homozygotes should be excluded: and end-to-side portacaval anastomosis seems to be preferable."}
{"id": "PMID:206977", "title": "The changing pattern of liver disease in South African Blacks.", "content": "Consecutive liver biopsies in a large general hospital for Blacks over the period 1959 - 1960 were compared with those in the 2-year period 1975 - 1976. Changes were noted in the histological appearances of micronodular cirrhosis. With the liberalization of the liquor laws and the granting of access to hard liquor to Blacks, fatty change, alcoholic hepatitis, alcoholic hyalin and alcoholic cirrhosis are making their appearance in the micronodular cirrhosis of the South African Blacks, features which were never observed when alcohol consumption was confined to homebrewed beverages containing large quantities of iron derived from the metallic containers in which liquor is brewed. No change in the histological picture or incidence of macronodular cirrhosis and hepatocellular carcinoma was observed.", "contents": "The changing pattern of liver disease in South African Blacks. Consecutive liver biopsies in a large general hospital for Blacks over the period 1959 - 1960 were compared with those in the 2-year period 1975 - 1976. Changes were noted in the histological appearances of micronodular cirrhosis. With the liberalization of the liquor laws and the granting of access to hard liquor to Blacks, fatty change, alcoholic hepatitis, alcoholic hyalin and alcoholic cirrhosis are making their appearance in the micronodular cirrhosis of the South African Blacks, features which were never observed when alcohol consumption was confined to homebrewed beverages containing large quantities of iron derived from the metallic containers in which liquor is brewed. No change in the histological picture or incidence of macronodular cirrhosis and hepatocellular carcinoma was observed."}
{"id": "PMID:206978", "title": "Hepatoblastoma in a middle-aged White South African Woman. A case report.", "content": "Hepatoblastoma is a primary embryonic liver tumour usually found in children. It extremely rarely occurs in adults and, when it does, is usually found in men, although it has been postulated that in women it may be associated with use of the oral contraceptive pill. We present a case of a 51-year-old White woman with no history of oral contraception. The features of this tumour are reviewed.", "contents": "Hepatoblastoma in a middle-aged White South African Woman. A case report. Hepatoblastoma is a primary embryonic liver tumour usually found in children. It extremely rarely occurs in adults and, when it does, is usually found in men, although it has been postulated that in women it may be associated with use of the oral contraceptive pill. We present a case of a 51-year-old White woman with no history of oral contraception. The features of this tumour are reviewed."}
{"id": "PMID:206979", "title": "Haematogenous amoebic lung abscess. A case report.", "content": "Left upper lobe amoebic lung abscess without established hepatic amoebiasis in a young Black man is described and the pathogenesis is briefly discussed.", "contents": "Haematogenous amoebic lung abscess. A case report. Left upper lobe amoebic lung abscess without established hepatic amoebiasis in a young Black man is described and the pathogenesis is briefly discussed."}
{"id": "PMID:206980", "title": "Prevalence of antibodies to a rotavirus in black and white populations in South Africa.", "content": "A serological survey of antibodies to a rotavirus in 252 sera from Black and White South Africans was performed by means of an immunofluorescence test using cells infected with simian rotavirus, SA 11, as antigen. The results indicate widespread presence of this agent in South Africa and also that the Black population is exposed to a greater extent than the White population.", "contents": "Prevalence of antibodies to a rotavirus in black and white populations in South Africa. A serological survey of antibodies to a rotavirus in 252 sera from Black and White South Africans was performed by means of an immunofluorescence test using cells infected with simian rotavirus, SA 11, as antigen. The results indicate widespread presence of this agent in South Africa and also that the Black population is exposed to a greater extent than the White population."}
{"id": "PMID:206988", "title": "alpha 1-antitrypsin in cadmium toxicity: an evaluation of its suggested role.", "content": "Chowdhury and Louria [1] reported that cadmium could reduce in vitro the concentration and the trypsin inhibitory capacity of plasma alpha 1-antitrypsin. They suggested that this could explain the emphysema observed in some workers exposed to cadmium. Using the same experimental approach as these authors, we could not reproduce their observations. Furthermore, in vivo results obtained on workers excessively exposed to cadmium during more than 20 years and exhibiting obvious signs of chronic cadmium intoxication did not reveal a decrease in the concentration and the activity of plasma alpha 1-antitrypsin.", "contents": "alpha 1-antitrypsin in cadmium toxicity: an evaluation of its suggested role. Chowdhury and Louria [1] reported that cadmium could reduce in vitro the concentration and the trypsin inhibitory capacity of plasma alpha 1-antitrypsin. They suggested that this could explain the emphysema observed in some workers exposed to cadmium. Using the same experimental approach as these authors, we could not reproduce their observations. Furthermore, in vivo results obtained on workers excessively exposed to cadmium during more than 20 years and exhibiting obvious signs of chronic cadmium intoxication did not reveal a decrease in the concentration and the activity of plasma alpha 1-antitrypsin."}
{"id": "PMID:206989", "title": "[Problems of tongue neoplasms in the light of personal observations].", "content": "Due to unfavourable local and general conditions, the treatment of carcinoma of the tongue still yields unsatisfactory results. The authors ascertained that 101 patients with carcinoma of the tongue (68 males and 37 females), having an average age of 65.2 years, had been treated at their clinic within a period of 27 years (1948--1974). Only 21% of them survived five years. In this connexion, certain questions, which are essential in the authors' opinion, are discussed. Furthermore, the patients are subdivided with regard to different aspects.", "contents": "[Problems of tongue neoplasms in the light of personal observations]. Due to unfavourable local and general conditions, the treatment of carcinoma of the tongue still yields unsatisfactory results. The authors ascertained that 101 patients with carcinoma of the tongue (68 males and 37 females), having an average age of 65.2 years, had been treated at their clinic within a period of 27 years (1948--1974). Only 21% of them survived five years. In this connexion, certain questions, which are essential in the authors' opinion, are discussed. Furthermore, the patients are subdivided with regard to different aspects."}
{"id": "PMID:206990", "title": "A follow-up program for suicide attempters: evaluation of effectiveness.", "content": "Suicide attempters are a high-risk group in relation to ultimately completing suicide and are usually \"treated and released\" with little or no follow-up care. A 4-month follow-up outreach program for suicide attempters seen in the emergency room was developed with an emphasis on continuity and quantity of \"treatment\" received. Suicide attempters were randomly assigned to the \"follow-up outreach\" or \"normal\" treatment programs. Measures for the evaluation of effectiveness were (a) incidence of suicide reattempts and purposive accidents and (b) prevalence of drug misuse and excessive use of alcohol. The experimental group showed a statistically significant reduction in suicide reattempts and excessive use of alcohol, while the reduction of drug abuse, although not statistically significant, did conform to a trend indicating improvement. Purposive accidents occured at a relatively equal rate among both groups.", "contents": "A follow-up program for suicide attempters: evaluation of effectiveness. Suicide attempters are a high-risk group in relation to ultimately completing suicide and are usually \"treated and released\" with little or no follow-up care. A 4-month follow-up outreach program for suicide attempters seen in the emergency room was developed with an emphasis on continuity and quantity of \"treatment\" received. Suicide attempters were randomly assigned to the \"follow-up outreach\" or \"normal\" treatment programs. Measures for the evaluation of effectiveness were (a) incidence of suicide reattempts and purposive accidents and (b) prevalence of drug misuse and excessive use of alcohol. The experimental group showed a statistically significant reduction in suicide reattempts and excessive use of alcohol, while the reduction of drug abuse, although not statistically significant, did conform to a trend indicating improvement. Purposive accidents occured at a relatively equal rate among both groups."}
{"id": "PMID:206991", "title": "Electrophoretic isoenzyme patterns of Entamoeba histolytica and Entamoeba coli.", "content": "Cultures of 14 stocks of Entamoeba histolytica and one only of Entamoeba coli were compared by electrophoretic patterns of three enzymes: glucose-phosphate isomerase, phosphoglucomutase and L-malate: NADP+ oxidoreductase (oxaloacetate-decarboxylating). Easily distinguished patterns divided E. histolytica into three groups, whilst a distinctly different pattern for E. coli was also seen.", "contents": "Electrophoretic isoenzyme patterns of Entamoeba histolytica and Entamoeba coli. Cultures of 14 stocks of Entamoeba histolytica and one only of Entamoeba coli were compared by electrophoretic patterns of three enzymes: glucose-phosphate isomerase, phosphoglucomutase and L-malate: NADP+ oxidoreductase (oxaloacetate-decarboxylating). Easily distinguished patterns divided E. histolytica into three groups, whilst a distinctly different pattern for E. coli was also seen."}
{"id": "PMID:206993", "title": "[Relationship between the volume and proportions of the organoids and cell volume in yeasts].", "content": "Populations of yeast Saccharomyces carlsbergensis and Candida quilliermondii were divided into cell classes with different volumes. In each class volumes of nuclei, vacuoles and lipid incorporation were measured. With the increase of cell volumes, volumes of organoides increased too, but the relative volume of nucleus decreased, and the relative volumes of vacuoles and of lipid incorporation increased.", "contents": "[Relationship between the volume and proportions of the organoids and cell volume in yeasts]. Populations of yeast Saccharomyces carlsbergensis and Candida quilliermondii were divided into cell classes with different volumes. In each class volumes of nuclei, vacuoles and lipid incorporation were measured. With the increase of cell volumes, volumes of organoides increased too, but the relative volume of nucleus decreased, and the relative volumes of vacuoles and of lipid incorporation increased."}
{"id": "PMID:206994", "title": "[Enzymes of the outer segments of the retinal rods: The problem of localization and coupling with rhodopsin].", "content": "The problem of the presence of enzymes in retina rod outer segments is summarized using both literature and the author's own data. Difficulties in the solving of this problem are analyzed. It has been shown that some enzymes involved in the primary mechanisms of the photoreceptor process are localized in the inner segment of the photoreceptor cell at a distance from the photoreceptor membranes. A conclusion is drawn that the enzymes necessary for rhodopsin (or its retinal-part) conversions as well as those ensuring synthesis and decay of cyclic nucleotides are concentrated in the outer segments. These data served as a ground for a conclusion about a strictly \"biochemial\" specialization of particular parts of the photoreceptor cell in which tightly linked chemical transformations proceed in different compartments. Besides, some unusual properties of the plasma membrane of the photoreceptor cell are noticed, in particular, the absence in part of this membrane of some typical marking enzymes. The interrelations between rhodopsin and enzymes as well as a possible participation of Ca-ions in this process are examined. It is supposed that one part of the rhodopsin molecule may act as a Ca2+ binding protein.", "contents": "[Enzymes of the outer segments of the retinal rods: The problem of localization and coupling with rhodopsin]. The problem of the presence of enzymes in retina rod outer segments is summarized using both literature and the author's own data. Difficulties in the solving of this problem are analyzed. It has been shown that some enzymes involved in the primary mechanisms of the photoreceptor process are localized in the inner segment of the photoreceptor cell at a distance from the photoreceptor membranes. A conclusion is drawn that the enzymes necessary for rhodopsin (or its retinal-part) conversions as well as those ensuring synthesis and decay of cyclic nucleotides are concentrated in the outer segments. These data served as a ground for a conclusion about a strictly \"biochemial\" specialization of particular parts of the photoreceptor cell in which tightly linked chemical transformations proceed in different compartments. Besides, some unusual properties of the plasma membrane of the photoreceptor cell are noticed, in particular, the absence in part of this membrane of some typical marking enzymes. The interrelations between rhodopsin and enzymes as well as a possible participation of Ca-ions in this process are examined. It is supposed that one part of the rhodopsin molecule may act as a Ca2+ binding protein."}
{"id": "PMID:206995", "title": "Malignant ovarian neoplasms in childhood.", "content": "From 1962 to 1976, 15 children up to the age of 15 years with malignant neoplasms of the ovary were observed at the Istituto Nazionale Tumori of Milan. 13 patients had a germ cell tumor and 2 a stromal tumor. Natural history and treatment results are reported. Out of 7 patients with dysgerminoma, 3 at stage IA, 2 at stage III retroperitoneal and 1 with recurrent disease are alive and disease free 38+, 20+, 36+, 16+, 23+, 156+ months after the histologic diagnosis; the last case with stage III peritoneal disease died 2 months after the diagnosis. Four children had immature malignant teratoma: 2 patients are alive and disease free 19+ and 51+ months, 1 is alive with disease 20+ months and 1 died 16 months after histologic diagnosis. Two patients with extra-embryonal teratoma died 7 and 12 months after diagnosis. One patient, treated by surgery plus chemotherapy for granulosa cell tumor at stage III, is alive 43+ months later. The child with arrhenoblastoma at stage III treated by surgery plus radiochemotherapy died 6 months after diagnosis. Through a close scrutiny of the literature and by drawing on experience gained in the treatment of the same tumors in adults, a rational approach to the diagnosis and treatment of each childhood ovarian tumor histotype is worked out.", "contents": "Malignant ovarian neoplasms in childhood. From 1962 to 1976, 15 children up to the age of 15 years with malignant neoplasms of the ovary were observed at the Istituto Nazionale Tumori of Milan. 13 patients had a germ cell tumor and 2 a stromal tumor. Natural history and treatment results are reported. Out of 7 patients with dysgerminoma, 3 at stage IA, 2 at stage III retroperitoneal and 1 with recurrent disease are alive and disease free 38+, 20+, 36+, 16+, 23+, 156+ months after the histologic diagnosis; the last case with stage III peritoneal disease died 2 months after the diagnosis. Four children had immature malignant teratoma: 2 patients are alive and disease free 19+ and 51+ months, 1 is alive with disease 20+ months and 1 died 16 months after histologic diagnosis. Two patients with extra-embryonal teratoma died 7 and 12 months after diagnosis. One patient, treated by surgery plus chemotherapy for granulosa cell tumor at stage III, is alive 43+ months later. The child with arrhenoblastoma at stage III treated by surgery plus radiochemotherapy died 6 months after diagnosis. Through a close scrutiny of the literature and by drawing on experience gained in the treatment of the same tumors in adults, a rational approach to the diagnosis and treatment of each childhood ovarian tumor histotype is worked out."}
{"id": "PMID:206998", "title": "The Seventh Frederick H. Verhoeff Lecture. Collagenase and collagenase inhibitors.", "content": "Besides EDTA and cysteine, cystine and penicillamine are the best collagenase inhibitors. The collagenase is produced by the leucocytes. The action mechanism of the collagenase inhibitors is due to the chelation of Zn ions. The best clinical indications for collagenase inhibitors are punctate epithelial keratitis, chemical burns, recurrent corneal erosions in keratoconus, trophic postinfectious ulcerations of the cornea (metaherpetic ulcers), and descemetoceles.", "contents": "The Seventh Frederick H. Verhoeff Lecture. Collagenase and collagenase inhibitors. Besides EDTA and cysteine, cystine and penicillamine are the best collagenase inhibitors. The collagenase is produced by the leucocytes. The action mechanism of the collagenase inhibitors is due to the chelation of Zn ions. The best clinical indications for collagenase inhibitors are punctate epithelial keratitis, chemical burns, recurrent corneal erosions in keratoconus, trophic postinfectious ulcerations of the cornea (metaherpetic ulcers), and descemetoceles."}
{"id": "PMID:206999", "title": "Congenital herpes simplex virus, type 2, bilateral endophthalmitis.", "content": "A set of dizygotic twins, both born prematurely, developed herpes simplex encephalitis shortly after birth. The second twin had unilateral keratoconjunctivitis and bilateral endophthalmitis and subsequently died from disseminated herpes infection. Herpes simplex, type 2, was isolated from conjunctiva of both eyes, cerebrospinal fluid, nasopharynx and trachea. Histologic examination of the eyes reveaed bilateral endophthalmitis with a necrotizing retinitis. Intranuclear inclusion bodies were demonstrated by light microscopy in the retina, choroid and iris, and virus particles were demonstrated by electron microscopy in the retina. The other twin recovered from a much milder disseminate herpes simplex infection without apparent ocular involvement. During pregnancy, the mother had vaginitis which was suspected, but not documented, as being herpetic in origin. The father was diagnosed as having a penile infection caused by herpes simplex.", "contents": "Congenital herpes simplex virus, type 2, bilateral endophthalmitis. A set of dizygotic twins, both born prematurely, developed herpes simplex encephalitis shortly after birth. The second twin had unilateral keratoconjunctivitis and bilateral endophthalmitis and subsequently died from disseminated herpes infection. Herpes simplex, type 2, was isolated from conjunctiva of both eyes, cerebrospinal fluid, nasopharynx and trachea. Histologic examination of the eyes reveaed bilateral endophthalmitis with a necrotizing retinitis. Intranuclear inclusion bodies were demonstrated by light microscopy in the retina, choroid and iris, and virus particles were demonstrated by electron microscopy in the retina. The other twin recovered from a much milder disseminate herpes simplex infection without apparent ocular involvement. During pregnancy, the mother had vaginitis which was suspected, but not documented, as being herpetic in origin. The father was diagnosed as having a penile infection caused by herpes simplex."}
{"id": "PMID:207003", "title": "[Use of contrast radiography in acute obstruction of the small intestine].", "content": "The authors believe that the contrast radiography of the small intestine in case of its obstruction should be used on strict indications only and only in patients with unclear clinical and roentgenological picture. When following the method strictly, the examination is safe for the patient, it may be stopped at any stage when evident symptoms, both clinical and roentgenological, of the obstruction appear.", "contents": "[Use of contrast radiography in acute obstruction of the small intestine]. The authors believe that the contrast radiography of the small intestine in case of its obstruction should be used on strict indications only and only in patients with unclear clinical and roentgenological picture. When following the method strictly, the examination is safe for the patient, it may be stopped at any stage when evident symptoms, both clinical and roentgenological, of the obstruction appear."}
{"id": "PMID:207004", "title": "[Elimination of testosterone and androstendione in the urine of boars in relation to the incretory function of the testes].", "content": "The elimination of testosterone and androstendion in the urine was tested in six sexually mature boars. The administration of chorionic gonadotropin to intact animals resulted in a marked, statistically significant, rise of the amounts of excreted testosterone and, in part of the cases, androstendion. The responses were individual. Bilateral orchidectomy caused a statistically highly significant decrease of the elimination of both steroids under study without pronounced adrenocortical compensation. The administration of the adrenocorticotropic hormone to castrated boars did not exert any significant influence on the excretion of the substances studied. The use of chorionic gonadotropin given to the castrated boars did not produce any significant changes in the elimination of hormones. It has been inferred that testosterone as well as androstendion in the urine of boars are almost exclusively of testicular origin and that the response of the values of both steroids to the administration of chorionic gonadotropin is specific after testicular incretion. The discussion concerns the importance of these findings for the evaluation of the incretion reserve of the testes and for the diagnosis of incretion hypogonadism in boars.", "contents": "[Elimination of testosterone and androstendione in the urine of boars in relation to the incretory function of the testes]. The elimination of testosterone and androstendion in the urine was tested in six sexually mature boars. The administration of chorionic gonadotropin to intact animals resulted in a marked, statistically significant, rise of the amounts of excreted testosterone and, in part of the cases, androstendion. The responses were individual. Bilateral orchidectomy caused a statistically highly significant decrease of the elimination of both steroids under study without pronounced adrenocortical compensation. The administration of the adrenocorticotropic hormone to castrated boars did not exert any significant influence on the excretion of the substances studied. The use of chorionic gonadotropin given to the castrated boars did not produce any significant changes in the elimination of hormones. It has been inferred that testosterone as well as androstendion in the urine of boars are almost exclusively of testicular origin and that the response of the values of both steroids to the administration of chorionic gonadotropin is specific after testicular incretion. The discussion concerns the importance of these findings for the evaluation of the incretion reserve of the testes and for the diagnosis of incretion hypogonadism in boars."}
{"id": "PMID:207006", "title": "A study of dogs with kennel cough.", "content": "A detailed study of a population of dogs with kennel cough was undertaken. Twenty-seven (77 per cent) of a total of 35 dogs had pathological evidence of respiratory disease in the form of tracheobronchitis with, in some animals, exudative pneumonia. A variety of viral and bacterial agents were isolated from the respiratory tract of diseased dogs but Bordetella bronchiseptica and canine parainfluenza virus SV-5 appeared to be the most significant organisms recovered.", "contents": "A study of dogs with kennel cough. A detailed study of a population of dogs with kennel cough was undertaken. Twenty-seven (77 per cent) of a total of 35 dogs had pathological evidence of respiratory disease in the form of tracheobronchitis with, in some animals, exudative pneumonia. A variety of viral and bacterial agents were isolated from the respiratory tract of diseased dogs but Bordetella bronchiseptica and canine parainfluenza virus SV-5 appeared to be the most significant organisms recovered."}
{"id": "PMID:207008", "title": "Active immunisation of ducklings against duck virus hepatitis.", "content": "Egg-attenuated duck hepatitis type (Rispens H55) was exhaustively tested as a potential vaccine under controlled conditions in ducklings fully susceptible to the disease at day 2 after hatching. Data are presented which indicate that this vaccine fulfils essential criteria of efficacy in terms of (a) the optimal age at which successful vaccination is practicable (day 2 or earlier), (b) the rapidity of onset of immunity (in 48 to 72 hours), (c) the high level of immunity induced (88.0 to 94.0 per cent), (d) the persistence of this degree of immunity in the individual bird throughout the period when it would otherwise be at risk (until the end of the fourth week of life) and (e) the consistency of the effects of the vaccine in successive groups of ducklings hatched over a four year period. Employed as a vaccine. H55 was completely innocuous to the vaccinated ducklings under laboratory conditions.", "contents": "Active immunisation of ducklings against duck virus hepatitis. Egg-attenuated duck hepatitis type (Rispens H55) was exhaustively tested as a potential vaccine under controlled conditions in ducklings fully susceptible to the disease at day 2 after hatching. Data are presented which indicate that this vaccine fulfils essential criteria of efficacy in terms of (a) the optimal age at which successful vaccination is practicable (day 2 or earlier), (b) the rapidity of onset of immunity (in 48 to 72 hours), (c) the high level of immunity induced (88.0 to 94.0 per cent), (d) the persistence of this degree of immunity in the individual bird throughout the period when it would otherwise be at risk (until the end of the fourth week of life) and (e) the consistency of the effects of the vaccine in successive groups of ducklings hatched over a four year period. Employed as a vaccine. H55 was completely innocuous to the vaccinated ducklings under laboratory conditions."}
{"id": "PMID:207015", "title": "Ultrastructure and morphometry of ACTH-producing cell in the rat anterior pituitary gland stimulated by lysin-vasopressin and prostaglandin E1.", "content": "The aim of this study was to investigate the qualitative and quantitative changes of ACTH-cells in the rat after application of a specific and a non-specific stimulus. A CRF-analog (lysin-vasopressin) and a prostaglandin (prostaglandin E1) were used. 40 rats were injected lysin-vasopressin or prostaglandin E1, respectively, for 4 weeks. The pituitary glands were investigated by means of light microscopy, electron microscopy and morphometry. Activation of the ACTH-cells could be observed after use of both substances, the effect of lysin-vasopressin being more intense than that of prostaglandin E1. Enlargement of the nucleus, the cytoplasm and the organelles involved in hormone-production and -transport were found and verified by morphometry. Additionally an increase in number of the cells could be demonstrated. Prostaglandin influenced not only ACTH-cells, but also other cells of the anterior pituitary.", "contents": "Ultrastructure and morphometry of ACTH-producing cell in the rat anterior pituitary gland stimulated by lysin-vasopressin and prostaglandin E1. The aim of this study was to investigate the qualitative and quantitative changes of ACTH-cells in the rat after application of a specific and a non-specific stimulus. A CRF-analog (lysin-vasopressin) and a prostaglandin (prostaglandin E1) were used. 40 rats were injected lysin-vasopressin or prostaglandin E1, respectively, for 4 weeks. The pituitary glands were investigated by means of light microscopy, electron microscopy and morphometry. Activation of the ACTH-cells could be observed after use of both substances, the effect of lysin-vasopressin being more intense than that of prostaglandin E1. Enlargement of the nucleus, the cytoplasm and the organelles involved in hormone-production and -transport were found and verified by morphometry. Additionally an increase in number of the cells could be demonstrated. Prostaglandin influenced not only ACTH-cells, but also other cells of the anterior pituitary."}
{"id": "PMID:207016", "title": "[Electron microscopic observations in internal organs in morbus Fabry (author's transl)].", "content": "Electron microscopic findings are reported on the localization and fine structure of glycolipid inclusions in different organs (heart, kidney, lymph nodes, arterial blood vessels, pancreas) in Fabry's disease in a female. The intracellular and extracellular inclusions were made up of multilamellar membraneous systems in concentric, excentric, and parallel arrangement. This fine structure is characteristic of liquid-crystalline phases of phospholipid-water systems. The same type of inclusions are found in the internal organs of heterozygotic women as in homozygotic men. The relationship between the glycolipid inclusions and the lysosomes is discussed.", "contents": "[Electron microscopic observations in internal organs in morbus Fabry (author's transl)]. Electron microscopic findings are reported on the localization and fine structure of glycolipid inclusions in different organs (heart, kidney, lymph nodes, arterial blood vessels, pancreas) in Fabry's disease in a female. The intracellular and extracellular inclusions were made up of multilamellar membraneous systems in concentric, excentric, and parallel arrangement. This fine structure is characteristic of liquid-crystalline phases of phospholipid-water systems. The same type of inclusions are found in the internal organs of heterozygotic women as in homozygotic men. The relationship between the glycolipid inclusions and the lysosomes is discussed."}
{"id": "PMID:207017", "title": "[Operations for rectal and sigmoid cancer in persons younger than 40].", "content": "The results of 57 sphincter-preserving operations for cancer of the rectum and sigmoid in persons under 40 years of age are analysed. Of 40 patients, operated upon 5 years ago and longer, 28 patients (70%) are alive. The prognosis for cancer of the sigmoid and rectum in young patients is greatly influenced by the depth of tumor infiltration of the intestinal wall, metastatic involvement of regional lymph nodes and the histological structure of the tumor.", "contents": "[Operations for rectal and sigmoid cancer in persons younger than 40]. The results of 57 sphincter-preserving operations for cancer of the rectum and sigmoid in persons under 40 years of age are analysed. Of 40 patients, operated upon 5 years ago and longer, 28 patients (70%) are alive. The prognosis for cancer of the sigmoid and rectum in young patients is greatly influenced by the depth of tumor infiltration of the intestinal wall, metastatic involvement of regional lymph nodes and the histological structure of the tumor."}
{"id": "PMID:207018", "title": "[Clinical and morphological comparative correlations in rectal cancer and their prognostic importance].", "content": "Besides generally accepted tests for prognostication of the results of radical surgical treatment for rectal cancer, great practical importance is attached to the complex of accessory tests such as the combined intensity of immune lymphocytic infiltrates, the tumor and adjacent tissues, the amount of pathological mitoses, the degree of vascularization and the absolute number of lymphocytes in peripheral blood. An estimation of different combinations of the tests concerned makes it possible to prognosticate the results of radical treatment for rectal cancer in each particular case.", "contents": "[Clinical and morphological comparative correlations in rectal cancer and their prognostic importance]. Besides generally accepted tests for prognostication of the results of radical surgical treatment for rectal cancer, great practical importance is attached to the complex of accessory tests such as the combined intensity of immune lymphocytic infiltrates, the tumor and adjacent tissues, the amount of pathological mitoses, the degree of vascularization and the absolute number of lymphocytes in peripheral blood. An estimation of different combinations of the tests concerned makes it possible to prognosticate the results of radical treatment for rectal cancer in each particular case."}
{"id": "PMID:207019", "title": "[Influence of chemical carcinogens on the physiological effects of adrenomimetics].", "content": "The experiments on isolated atria of rats and guinea pigs have shown that chemical hepatotropic carcinogens (diethylnitrosoamine and 2-acetyl aminofluorene) modify the physiological effects of adrenomimetics. A correlation between the authors' findings and the literature data on application of adrenergic drugs in carcinogenesis allows a suggestion to be made on the possibility of a principally new aspect in the mechanism of action of chemical carcinogens related to their effect on adrenoreceptors of target-organs.", "contents": "[Influence of chemical carcinogens on the physiological effects of adrenomimetics]. The experiments on isolated atria of rats and guinea pigs have shown that chemical hepatotropic carcinogens (diethylnitrosoamine and 2-acetyl aminofluorene) modify the physiological effects of adrenomimetics. A correlation between the authors' findings and the literature data on application of adrenergic drugs in carcinogenesis allows a suggestion to be made on the possibility of a principally new aspect in the mechanism of action of chemical carcinogens related to their effect on adrenoreceptors of target-organs."}
{"id": "PMID:207020", "title": "[Effect of thiophosphamide, its paramagnetic analogs and the iminoxyl radical on the division of tumor cells].", "content": "The authors have studied the effect of thiophosphamide its paramagentic analogs and iminoxyl radical on cell reproduction of Ehrlich ascites tumor. It was shown that the effect of paramagnetic analogs is made up of a sum of injuries produced by ethylenimine and iminoxyl portions of molecules. One of the analogs involved proves to be more active than thiophosphamide.", "contents": "[Effect of thiophosphamide, its paramagnetic analogs and the iminoxyl radical on the division of tumor cells]. The authors have studied the effect of thiophosphamide its paramagentic analogs and iminoxyl radical on cell reproduction of Ehrlich ascites tumor. It was shown that the effect of paramagnetic analogs is made up of a sum of injuries produced by ethylenimine and iminoxyl portions of molecules. One of the analogs involved proves to be more active than thiophosphamide."}
{"id": "PMID:207022", "title": "[Effectiveness of radioisotope therapy of inoperable brain tumors according to the results of follow-up studies].", "content": "Intra-tissue and intracavitary beta- and gamma-therapy with Au198, P32 and Y90 was used in the system of combined treatment of 139 patients with inoperable tumors of the brain, among whom 40% were children. The results of follow-up periods of 5 to 17 years led to the conclusion that radioisotope treatment is effective in craniopharyngioma, tumors of the cerebral ventricles and inoperable meningioma of the base of the brain.", "contents": "[Effectiveness of radioisotope therapy of inoperable brain tumors according to the results of follow-up studies]. Intra-tissue and intracavitary beta- and gamma-therapy with Au198, P32 and Y90 was used in the system of combined treatment of 139 patients with inoperable tumors of the brain, among whom 40% were children. The results of follow-up periods of 5 to 17 years led to the conclusion that radioisotope treatment is effective in craniopharyngioma, tumors of the cerebral ventricles and inoperable meningioma of the base of the brain."}
{"id": "PMID:207026", "title": "[A case of granular cell myoblastoma of bronchus with bronchiectasia (author's transl)].", "content": "A case of granular cell myoblastoma of a 33 year old man has been presented. The tumor arising from a subsegmental bronchus of the right upper lobe caused bronchial obstruction with a distal localized bronchiectasia, appearing clinically as bronchogenic cyst.", "contents": "[A case of granular cell myoblastoma of bronchus with bronchiectasia (author's transl)]. A case of granular cell myoblastoma of a 33 year old man has been presented. The tumor arising from a subsegmental bronchus of the right upper lobe caused bronchial obstruction with a distal localized bronchiectasia, appearing clinically as bronchogenic cyst."}
{"id": "PMID:207027", "title": "[Regulation of hepatocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase in primary cell cultures through low density lipoproteins].", "content": "The regulation of hepatic cholesterol biosynthesis by low density lipoprotein (LDL) was studied by using a new cell culture method of isolated rat hepatocytes. After two days in culture no supressant effect of LDL on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity (HMG-CoA) was detected. The primary culture of rat hepatocytes lead to the growth of a cell monolayer with stable liver specific properties during 4 days of culture. LDL did suppress HMG-CoA-reductase activity of rat hepatocytes in primary culture 5 days after seeding, when dedifferentiation has started.", "contents": "[Regulation of hepatocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase in primary cell cultures through low density lipoproteins]. The regulation of hepatic cholesterol biosynthesis by low density lipoprotein (LDL) was studied by using a new cell culture method of isolated rat hepatocytes. After two days in culture no supressant effect of LDL on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity (HMG-CoA) was detected. The primary culture of rat hepatocytes lead to the growth of a cell monolayer with stable liver specific properties during 4 days of culture. LDL did suppress HMG-CoA-reductase activity of rat hepatocytes in primary culture 5 days after seeding, when dedifferentiation has started."}
{"id": "PMID:207030", "title": "Effect of experimentally induced trichinellosis on the infection with Erysipelothrix rhusiopathiae in rats.", "content": "Infection with Erysipelothrix rhusiopathiae in rats infested 20 days earlier with Trichinella spiralis developed more slowly, the clinical and pathoanatomic changes in the joints were expressed to a less extend, and the mortality rate was lower. The erythrocyte sedimentation rate, the precipitin formation and the phagocytic activity of the macrophages did not considerably change. Experiments carried out to elucidate this fact did not reveal any antigenic or antagonistic relationships between parasite and bacterium nor any protective effect of the host's serum. The inhibitory influence of corticosteroids on the defence forces was not completely manifested in the rats infested. This fact might be explained by interrelations depending both on the cycle of helminth development and on the non-specific immunological reactivity of the organism, the latter being stimulated by the helminth invasion.", "contents": "Effect of experimentally induced trichinellosis on the infection with Erysipelothrix rhusiopathiae in rats. Infection with Erysipelothrix rhusiopathiae in rats infested 20 days earlier with Trichinella spiralis developed more slowly, the clinical and pathoanatomic changes in the joints were expressed to a less extend, and the mortality rate was lower. The erythrocyte sedimentation rate, the precipitin formation and the phagocytic activity of the macrophages did not considerably change. Experiments carried out to elucidate this fact did not reveal any antigenic or antagonistic relationships between parasite and bacterium nor any protective effect of the host's serum. The inhibitory influence of corticosteroids on the defence forces was not completely manifested in the rats infested. This fact might be explained by interrelations depending both on the cycle of helminth development and on the non-specific immunological reactivity of the organism, the latter being stimulated by the helminth invasion."}
{"id": "PMID:207031", "title": "Polyphenol oxidase and scleroprotein/melanin pigments of Isoparorchis hypselobagri.", "content": "The polyphenol oxidase activity of Isoparorchis hypselobagri was estimated biochemically and was believed to be associated with egg-shell formation in the parasite. The eggs gave positive tests to color reaction of scleroprotein/melanin.", "contents": "Polyphenol oxidase and scleroprotein/melanin pigments of Isoparorchis hypselobagri. The polyphenol oxidase activity of Isoparorchis hypselobagri was estimated biochemically and was believed to be associated with egg-shell formation in the parasite. The eggs gave positive tests to color reaction of scleroprotein/melanin."}
{"id": "PMID:207032", "title": "[Familical cleft foot--a clinical study over 4 generations (author's transl)].", "content": "Within this paper a family is being described in which foot deformities are shown over four generations. During two generations cleft foot is found as well as a syndaktylism. The cases are demonstrated clinically, by photographs and also by X-ray. The question of inheritance is being discussed in comparison with the existing literature, also taking into account the coexistence of cleft foot and syndaktylism.", "contents": "[Familical cleft foot--a clinical study over 4 generations (author's transl)]. Within this paper a family is being described in which foot deformities are shown over four generations. During two generations cleft foot is found as well as a syndaktylism. The cases are demonstrated clinically, by photographs and also by X-ray. The question of inheritance is being discussed in comparison with the existing literature, also taking into account the coexistence of cleft foot and syndaktylism."}
{"id": "PMID:207045", "title": "[Lung metastases of a malignant giant cell tumour simulating an alveolar carcinosis (author's transl)].", "content": "A brief report an lung metastases of a malignant giant cell tumour simulating an alveolar cell carcinoma in peripheric regions is given, and a critical classification of alveolar cell carcinoma is supported.", "contents": "[Lung metastases of a malignant giant cell tumour simulating an alveolar carcinosis (author's transl)]. A brief report an lung metastases of a malignant giant cell tumour simulating an alveolar cell carcinoma in peripheric regions is given, and a critical classification of alveolar cell carcinoma is supported."}
{"id": "PMID:207046", "title": "[Epithelial-mesenchymal tumor of the thyreoid associated with a colonic cancer (author's transl)].", "content": "A 76 year-old woman suffered from the simultaneous occurrence of a malignant metastazising tumor of the thyreoid and a colonic cancer without metastases. The thyreoid tumor was composed of epithelial and mesenchymal elements, among them a malignant angiosarcoma. Both elements were found not only in the primary tumor but also in the metastases.", "contents": "[Epithelial-mesenchymal tumor of the thyreoid associated with a colonic cancer (author's transl)]. A 76 year-old woman suffered from the simultaneous occurrence of a malignant metastazising tumor of the thyreoid and a colonic cancer without metastases. The thyreoid tumor was composed of epithelial and mesenchymal elements, among them a malignant angiosarcoma. Both elements were found not only in the primary tumor but also in the metastases."}
{"id": "PMID:207047", "title": "[Angiographic features of trophoblastic tumors (author's transl)].", "content": "Trophoblastic tumors are characterized by typical angiographic features with marked pathological vascularization, arteriovenous shunts and early filling of veines. If the HCG-titer increases after removing of a hydatidiform mole pelvic angiography is indicated in cases of negative histological finding also. In 3 cases the typical angiographic feature was found. Two times remaining changes of gravidity are histologicaly found on an abrasio. In 1 case with increased HCG-titer and negative histological finding a trophoblastic tumor was ascertained angiographicaly. Diagnostic value of pelvic angiography is demonstrated by above mentioned cases.", "contents": "[Angiographic features of trophoblastic tumors (author's transl)]. Trophoblastic tumors are characterized by typical angiographic features with marked pathological vascularization, arteriovenous shunts and early filling of veines. If the HCG-titer increases after removing of a hydatidiform mole pelvic angiography is indicated in cases of negative histological finding also. In 3 cases the typical angiographic feature was found. Two times remaining changes of gravidity are histologicaly found on an abrasio. In 1 case with increased HCG-titer and negative histological finding a trophoblastic tumor was ascertained angiographicaly. Diagnostic value of pelvic angiography is demonstrated by above mentioned cases."}
{"id": "PMID:207048", "title": "[Significance of an oral cytogram for the characterization of synthetic sex steroids].", "content": "In this study we have found, that the gingiva epithelium is a sensitive hormonal receptor which may present different histologic and cytologic changes in relation to the hormonal influences acting upon this organ. The oral smears can be used as a reliable test for the evaluation of estrogenic effects in monohormonal conditions.", "contents": "[Significance of an oral cytogram for the characterization of synthetic sex steroids]. In this study we have found, that the gingiva epithelium is a sensitive hormonal receptor which may present different histologic and cytologic changes in relation to the hormonal influences acting upon this organ. The oral smears can be used as a reliable test for the evaluation of estrogenic effects in monohormonal conditions."}
{"id": "PMID:207044", "title": "[Development and variability of the properties of a type of nervous system during ontogenesis].", "content": "Age dynamics of development and variability of properties of the nervous system type was studied in the same animals (31 dogs) at the age from one month to ten years. Individual typological differences in the properties of the dogs' nervous processes were clearly manifested at the age of four to seven and a half months. Three phases were singled out in the development and variability of the properties: I--development phase; II--stabilization phase; III--extinction phase. In ontogenesis, the dogs displayed great differences in the degree of manifestation and the beginning of the phases. Relative stabilization of nervous system properties already set in by the beginning of puberty in dogs of the weak type (seven months of postnatal life) and at mature age in dogs of the strong type. Some elements of general behaviour of dogs of different nervous system types and the duration of the animals life, in relation to the nervous system type have been outlined.", "contents": "[Development and variability of the properties of a type of nervous system during ontogenesis]. Age dynamics of development and variability of properties of the nervous system type was studied in the same animals (31 dogs) at the age from one month to ten years. Individual typological differences in the properties of the dogs' nervous processes were clearly manifested at the age of four to seven and a half months. Three phases were singled out in the development and variability of the properties: I--development phase; II--stabilization phase; III--extinction phase. In ontogenesis, the dogs displayed great differences in the degree of manifestation and the beginning of the phases. Relative stabilization of nervous system properties already set in by the beginning of puberty in dogs of the weak type (seven months of postnatal life) and at mature age in dogs of the strong type. Some elements of general behaviour of dogs of different nervous system types and the duration of the animals life, in relation to the nervous system type have been outlined."}
{"id": "PMID:207050", "title": "[Influence of killed Bordetella pertussis cells on the resistance against infection with Listeria monocytogenes (author's transl)].", "content": "The influence of killed Bordetella pertussis cells (B.p.) on the cell-mediated resistance of mice against infection with virulent germs of Listeria monocytogenes has been studied. Resistance of mice was decreased, when 3 X 10(9) B.p. were injected 1 day before, simultaneously with or 1 day after infection, resulting in augmented amounts of viable Listeriae recovered from the spleens 3 days after infection (figure 1). The LD50 was strongly reduced (Table 1). Transfer of immune spleen cells to recipient mice, which had been treated 1 day previously with 3 X 10(9)B.p., did not support resistance definitely (Table 2). Therefore, it can be concluded that probably the macrophage system was impaired just after B.p. injection. When, however, B.p. were given several days before infection, resistance was increased. A maximum of resistance enhancement was seen 7-14 days after B.p. treatment. Thereafter, this beneficial effect gradually decreased but persisted for at least 67 days (figure 1). This resistance enhancing effect of B.p. was surely not due to adjuvant effect of B.p. on the T-lymphocyte-mediated immune reaction to Listeriae, since in B.p.-pretreated mice the development of immunity during the primary infection to a secondary listeric infection has even been lacking (Table 3). It is more likely that the macrophage system was stimulated at this time by B.p. In mice treated 7 days prior to infection the elimination of Listeriae from the spleens was supported from the very beginning of the infection (figure 2).", "contents": "[Influence of killed Bordetella pertussis cells on the resistance against infection with Listeria monocytogenes (author's transl)]. The influence of killed Bordetella pertussis cells (B.p.) on the cell-mediated resistance of mice against infection with virulent germs of Listeria monocytogenes has been studied. Resistance of mice was decreased, when 3 X 10(9) B.p. were injected 1 day before, simultaneously with or 1 day after infection, resulting in augmented amounts of viable Listeriae recovered from the spleens 3 days after infection (figure 1). The LD50 was strongly reduced (Table 1). Transfer of immune spleen cells to recipient mice, which had been treated 1 day previously with 3 X 10(9)B.p., did not support resistance definitely (Table 2). Therefore, it can be concluded that probably the macrophage system was impaired just after B.p. injection. When, however, B.p. were given several days before infection, resistance was increased. A maximum of resistance enhancement was seen 7-14 days after B.p. treatment. Thereafter, this beneficial effect gradually decreased but persisted for at least 67 days (figure 1). This resistance enhancing effect of B.p. was surely not due to adjuvant effect of B.p. on the T-lymphocyte-mediated immune reaction to Listeriae, since in B.p.-pretreated mice the development of immunity during the primary infection to a secondary listeric infection has even been lacking (Table 3). It is more likely that the macrophage system was stimulated at this time by B.p. In mice treated 7 days prior to infection the elimination of Listeriae from the spleens was supported from the very beginning of the infection (figure 2)."}
{"id": "PMID:207051", "title": "[Use of the reversed passive hemagglutination in detection of Clostridium botulinum type A, B, and E toxin (author's transl)].", "content": "With the reversed passive hemagglutination technique it is possible to detect minimal amounts of botulinum type A, B and E toxins (s. Tab. 3). The antisera are used were prepared by foot--pad injection of rabbits with purified toxoids in Freund's complete adjuvant (s. Tab. 1). Antitoxin globulin were prepared from rabbit antisera with (NH4)2SO4 to 50%. Formalinized and tanned human erythrozytes were sensitized with these specific antitoxin globulins. Only slight cross reactions ere encountered between the type A, B, and E antiglobulin sensitized cells and culture filtrates of C. butyricum, C. sporogenes (type A and B antiglobulin only) and C. perfringens type C (s. Tab. 4).", "contents": "[Use of the reversed passive hemagglutination in detection of Clostridium botulinum type A, B, and E toxin (author's transl)]. With the reversed passive hemagglutination technique it is possible to detect minimal amounts of botulinum type A, B and E toxins (s. Tab. 3). The antisera are used were prepared by foot--pad injection of rabbits with purified toxoids in Freund's complete adjuvant (s. Tab. 1). Antitoxin globulin were prepared from rabbit antisera with (NH4)2SO4 to 50%. Formalinized and tanned human erythrozytes were sensitized with these specific antitoxin globulins. Only slight cross reactions ere encountered between the type A, B, and E antiglobulin sensitized cells and culture filtrates of C. butyricum, C. sporogenes (type A and B antiglobulin only) and C. perfringens type C (s. Tab. 4)."}
{"id": "PMID:207052", "title": "[Antiviral activity of tyrothricin against Sendai virus in suspension tests (author's transl)].", "content": "In suspension tests it could be found, that tyrothricin, isolated from bacteria, possesses an anti-infectious activity against Sendai virus. Concentrations of 10(2) to 10(3) ID50-units of Sendai virus were incubated with 0.5 and/or 1.0 mg tyrothricin per 5 ml for 30 minutes at 37 degrees C (pH 7.5). These mixtures were tested in embryonated eggs and showed a marked decrease of viral infectivity. Tween 80 added after the incubation period leads to an incomplete reactivation of the virus infectivity. According to these results and further preliminary studies on herpes simplex virus we suppose a virustatic effect of tyrothricin also in the case of other lipophilic viruses.", "contents": "[Antiviral activity of tyrothricin against Sendai virus in suspension tests (author's transl)]. In suspension tests it could be found, that tyrothricin, isolated from bacteria, possesses an anti-infectious activity against Sendai virus. Concentrations of 10(2) to 10(3) ID50-units of Sendai virus were incubated with 0.5 and/or 1.0 mg tyrothricin per 5 ml for 30 minutes at 37 degrees C (pH 7.5). These mixtures were tested in embryonated eggs and showed a marked decrease of viral infectivity. Tween 80 added after the incubation period leads to an incomplete reactivation of the virus infectivity. According to these results and further preliminary studies on herpes simplex virus we suppose a virustatic effect of tyrothricin also in the case of other lipophilic viruses."}
{"id": "PMID:207060", "title": "[Functional state of non-specific brain systems in dystonia musculorum deformans].", "content": "The paper deals with the results of an electropolygraphical study of night-sleep structure, as well as a clinical and experimental-psychological study of 27 patients with deforming muscular dystony. The quantitative and qualitative characteristics of functional shifts in different links of the nonspecific system in the known clinical forms and at different stages of the disease are given. The data were obtained with the aid of correlational statistical methods and were used for a clinico-physiological analysis of the syndrome of deforming muscular dystony. It is demonstrated that changes of a functional state of the nonspecific brain systems correlate with motor, emotional-personal vegetative and electroencephalographical manifestations of deforming muscular dystony.", "contents": "[Functional state of non-specific brain systems in dystonia musculorum deformans]. The paper deals with the results of an electropolygraphical study of night-sleep structure, as well as a clinical and experimental-psychological study of 27 patients with deforming muscular dystony. The quantitative and qualitative characteristics of functional shifts in different links of the nonspecific system in the known clinical forms and at different stages of the disease are given. The data were obtained with the aid of correlational statistical methods and were used for a clinico-physiological analysis of the syndrome of deforming muscular dystony. It is demonstrated that changes of a functional state of the nonspecific brain systems correlate with motor, emotional-personal vegetative and electroencephalographical manifestations of deforming muscular dystony."}
{"id": "PMID:207061", "title": "[Experience using sinakten-retard in the treatment of muscular sclerosis].", "content": "The experience of the authors demonstrated that the best results in sinakten-retard treatment were attained in patients with mild and moderate degrees of severity of the disease. However, even in patients with a protracted development, treatment by sinakten-retard increased the muscular strength in the paralyzed extremities, diminished the increased muscular tone and increased the volume of movements. All these facts permit the authors to recommend sinakten-retard for the treatment of disseminated sclerosis.", "contents": "[Experience using sinakten-retard in the treatment of muscular sclerosis]. The experience of the authors demonstrated that the best results in sinakten-retard treatment were attained in patients with mild and moderate degrees of severity of the disease. However, even in patients with a protracted development, treatment by sinakten-retard increased the muscular strength in the paralyzed extremities, diminished the increased muscular tone and increased the volume of movements. All these facts permit the authors to recommend sinakten-retard for the treatment of disseminated sclerosis."}
{"id": "PMID:207062", "title": "[Opiate receptors and endogenous morphines: a new approach to the study of the brain].", "content": "The paper deals with a range of problems connected with a study of a nature and a function of specific neuronal receptors and endogenous morphines. It is demonstrated that a further development of studies in the given area will be of a principal significance in solving the cardinal problems of psychopharmacology and a search for biological bases of mental diseases. The most perspective ways of studying functional opiate receptors and endogenous morphines in schizophrenia are discussed.", "contents": "[Opiate receptors and endogenous morphines: a new approach to the study of the brain]. The paper deals with a range of problems connected with a study of a nature and a function of specific neuronal receptors and endogenous morphines. It is demonstrated that a further development of studies in the given area will be of a principal significance in solving the cardinal problems of psychopharmacology and a search for biological bases of mental diseases. The most perspective ways of studying functional opiate receptors and endogenous morphines in schizophrenia are discussed."}
{"id": "PMID:207063", "title": "[Jacksonian seizures in the clinical picture of supratentorial brain tumors].", "content": "An analysis of the structure and frequency of Jackson's seizures during the illness in 27 patients with brain tumors displayed correlation of these parameters with a histological type of a neoformation and a degree of the involved mediobasal brain structures. In the process of development of the disease the epileptic activity in the EEG was replaced by a slow activity. The displayed peculiarities of the structure and the course of Jackson's seizures taking into account other clinical manifestations can be used in preoperational diagnosis of a histological nature of a tumor.", "contents": "[Jacksonian seizures in the clinical picture of supratentorial brain tumors]. An analysis of the structure and frequency of Jackson's seizures during the illness in 27 patients with brain tumors displayed correlation of these parameters with a histological type of a neoformation and a degree of the involved mediobasal brain structures. In the process of development of the disease the epileptic activity in the EEG was replaced by a slow activity. The displayed peculiarities of the structure and the course of Jackson's seizures taking into account other clinical manifestations can be used in preoperational diagnosis of a histological nature of a tumor."}
{"id": "PMID:207067", "title": "Regulation of phosphorylase-phosphatase from skeletal muscle by phosphorylation of a regulator protein.", "content": "The inhibitory effect of a heat-stable regulator protein from skeletal muscle on the activity of phosphorylase-phosphatase (EC 3.1.3.17) was studied. The regulator protein was shown to be both phosphorylated and dephosphorylated in vivo as well as in vitro. The incorporation of phosphate into the regulator protein increased, while dephosphorylation decreased the ability of the protein to inhibit phosphatase activity. Our results suggest that the reversible phosphorylation of the regulator protein plays an essential role in the regulation of phosphorylase-phosphatase activity.", "contents": "Regulation of phosphorylase-phosphatase from skeletal muscle by phosphorylation of a regulator protein. The inhibitory effect of a heat-stable regulator protein from skeletal muscle on the activity of phosphorylase-phosphatase (EC 3.1.3.17) was studied. The regulator protein was shown to be both phosphorylated and dephosphorylated in vivo as well as in vitro. The incorporation of phosphate into the regulator protein increased, while dephosphorylation decreased the ability of the protein to inhibit phosphatase activity. Our results suggest that the reversible phosphorylation of the regulator protein plays an essential role in the regulation of phosphorylase-phosphatase activity."}
{"id": "PMID:207068", "title": "Excitatory effects of the electrical activity of muscle on the contiguous nerve.", "content": "Experiments were performed on frog sciatic-gastrocnemius preparations in order to investigate the different conditions under which the excitation can be transmitted from muscle to nerve. The results demonstrate that, on one hand, the proximal part of the m. gastrocnemius is of greater importance in the transmission of excitation than the distal one and, on the other hand, when the nerve is in contact with more than one muscle, the transmission of excitation is determined by the compound electrical activity of the muscles. These results together with the findings of other authors support the hypothesis that the effect of the electrical muscle activity on the nerve in contact with the muscles could play an additional role in the mechanism of the excitatory processes of both the nerve and muscle.", "contents": "Excitatory effects of the electrical activity of muscle on the contiguous nerve. Experiments were performed on frog sciatic-gastrocnemius preparations in order to investigate the different conditions under which the excitation can be transmitted from muscle to nerve. The results demonstrate that, on one hand, the proximal part of the m. gastrocnemius is of greater importance in the transmission of excitation than the distal one and, on the other hand, when the nerve is in contact with more than one muscle, the transmission of excitation is determined by the compound electrical activity of the muscles. These results together with the findings of other authors support the hypothesis that the effect of the electrical muscle activity on the nerve in contact with the muscles could play an additional role in the mechanism of the excitatory processes of both the nerve and muscle."}
{"id": "PMID:207064", "title": "Plasma glucagon in insulinoma.", "content": "Nine patients with insulinoma were studied in order to investigate glucagon levels in the fasting state and the response of plasma glucagon to tolbutamide and arginine. Fasting plasma glucagon levels were within the normal range in all patients except two cases with malignant insulinoma. Although there was no correlation between blood glucose and plasma glucagon, a significant correlation between plasma glucagon and plasma insulin was observed. No detectable changes were found in glucagon levels during tolbutamide injection. In almost all patients except one an exaggerated response of plasma glucagon was demonstrated during arginine infusion test.", "contents": "Plasma glucagon in insulinoma. Nine patients with insulinoma were studied in order to investigate glucagon levels in the fasting state and the response of plasma glucagon to tolbutamide and arginine. Fasting plasma glucagon levels were within the normal range in all patients except two cases with malignant insulinoma. Although there was no correlation between blood glucose and plasma glucagon, a significant correlation between plasma glucagon and plasma insulin was observed. No detectable changes were found in glucagon levels during tolbutamide injection. In almost all patients except one an exaggerated response of plasma glucagon was demonstrated during arginine infusion test."}
{"id": "PMID:207069", "title": "Dysplastic gangliocytoma of the cerebellum--an ultrastructural study.", "content": "A case of dysplastic gangliocytoma of the cerebellum, a rare disorder with unknown etiology and pathogenesis, was studied ultrastructurally. The intranuclear inclusions identified were not seen to be of viral origin. The ultrastructural characteristics of the abnormal cells support the prevailing theory that these cells represent hypertrophied granular neurons.", "contents": "Dysplastic gangliocytoma of the cerebellum--an ultrastructural study. A case of dysplastic gangliocytoma of the cerebellum, a rare disorder with unknown etiology and pathogenesis, was studied ultrastructurally. The intranuclear inclusions identified were not seen to be of viral origin. The ultrastructural characteristics of the abnormal cells support the prevailing theory that these cells represent hypertrophied granular neurons."}
{"id": "PMID:207065", "title": "Practolol inhibition of some salbutamol-induced metabolic and hormonal responses.", "content": "The effect of practolol (a selective beta1-adrenergic receptor blocking agent) on increased blood insulin, sugar, lactate and FFA and decreased blood phosphorus and potassium induced by salbutamol (a primarily beta2-adrenergic stimulant) was studied in 6 normal volunteers. Practolol abolished the rise of lactate and glucose, suggesting that changes in these parameters due to salbutamol are mediated by beta1-receptors. The rise of insulin and the fall of potassium were only partially inhibited, and the possible involvement of the beta2-receptors as well in these 2 cases cannot be ruled out. The decrease of phosphorus and the FFA rise were not affected and thus appear to be primarily dependent on beta2-receptors.", "contents": "Practolol inhibition of some salbutamol-induced metabolic and hormonal responses. The effect of practolol (a selective beta1-adrenergic receptor blocking agent) on increased blood insulin, sugar, lactate and FFA and decreased blood phosphorus and potassium induced by salbutamol (a primarily beta2-adrenergic stimulant) was studied in 6 normal volunteers. Practolol abolished the rise of lactate and glucose, suggesting that changes in these parameters due to salbutamol are mediated by beta1-receptors. The rise of insulin and the fall of potassium were only partially inhibited, and the possible involvement of the beta2-receptors as well in these 2 cases cannot be ruled out. The decrease of phosphorus and the FFA rise were not affected and thus appear to be primarily dependent on beta2-receptors."}
{"id": "PMID:207070", "title": "Unmyelinated nerve fibres in feline acrylamide neuropathy.", "content": "Electronmicroscope studies have been performed on the greater splanchnic nerve and the nerve to the medial head of gastrocnemius muscle of control and acrylamide poisoned cats. Degeneration of unmyelinated as well as of myelinated fibres was observed in both nerves. In cats severely poisoned with acrylamide, some very large unmyelinated axons undergoing early degeneration were seen in the splanchnic nerve. In the nerve to medial head of gastrocnemius, there was a decrease in the proportion of large diameter unmyelinated axons.", "contents": "Unmyelinated nerve fibres in feline acrylamide neuropathy. Electronmicroscope studies have been performed on the greater splanchnic nerve and the nerve to the medial head of gastrocnemius muscle of control and acrylamide poisoned cats. Degeneration of unmyelinated as well as of myelinated fibres was observed in both nerves. In cats severely poisoned with acrylamide, some very large unmyelinated axons undergoing early degeneration were seen in the splanchnic nerve. In the nerve to medial head of gastrocnemius, there was a decrease in the proportion of large diameter unmyelinated axons."}
{"id": "PMID:207071", "title": "[Ultrastructural study of meningiothelial meningioma with 'hyaline inclusions' (author's transl)].", "content": "One case of meningiothelial meningioma with \"hyaline inclusions\" (colloid-bodies or pseudopsammomas) as noted by Cushing and Eisenhardt (1938) and by Kepes (1961-1975) is reported by light and electron microscopy. Two types of these structures, either homogeneous or polymorphic, surrounded by microvilli are described and regarded as signs of secretory differentiation of tumor cells. In addition to Kepes' description, the authors show, at high magnification, the polymorphic material including homogeneous component, lamellar structures, microvesicles and dense bodies. The endocellular overproduction of the various types of \"hyaline inclusions\" and the nature of their material are discussed.", "contents": "[Ultrastructural study of meningiothelial meningioma with 'hyaline inclusions' (author's transl)]. One case of meningiothelial meningioma with \"hyaline inclusions\" (colloid-bodies or pseudopsammomas) as noted by Cushing and Eisenhardt (1938) and by Kepes (1961-1975) is reported by light and electron microscopy. Two types of these structures, either homogeneous or polymorphic, surrounded by microvilli are described and regarded as signs of secretory differentiation of tumor cells. In addition to Kepes' description, the authors show, at high magnification, the polymorphic material including homogeneous component, lamellar structures, microvesicles and dense bodies. The endocellular overproduction of the various types of \"hyaline inclusions\" and the nature of their material are discussed."}
{"id": "PMID:207072", "title": "Light and electron microscopic observations on a ganglioneuroma.", "content": "This report describes some additional morphologic observations on a mediastinal ganglioneuroma. The neoplastic neurons contained argentaffin cytoplasmic granules presumably representing neurosecretory granules. Cytoplasmic inclusions resembling Pick's bodies were frequently observed in the neuronal components of the tumor. These inclusions consisted of neurofilaments mixed with a variable number of microtubules, dense core vesicles and other organelles. These findings expand the range of conditions in which Pick's bodies are found.", "contents": "Light and electron microscopic observations on a ganglioneuroma. This report describes some additional morphologic observations on a mediastinal ganglioneuroma. The neoplastic neurons contained argentaffin cytoplasmic granules presumably representing neurosecretory granules. Cytoplasmic inclusions resembling Pick's bodies were frequently observed in the neuronal components of the tumor. These inclusions consisted of neurofilaments mixed with a variable number of microtubules, dense core vesicles and other organelles. These findings expand the range of conditions in which Pick's bodies are found."}
{"id": "PMID:207073", "title": "Studies on hexachlorophene-induced myelin lesions in the trigeminal root transitional region in developing and adult mice.", "content": "Hexachlorophene (HCP)-induced intramyelinic vacuolation was studied in the transitional region of the trigeminal root of suckling and adult mice. HCP produced an extensive vacuolation in the central compartment of the region in both suckling and adult mice, while in the peripheral compartment myelin lesions were only seen in mice less than 16 days of age. Gas chromatographic measurements showed that in suckling mice the blood concentration of HCP decreased with age, apparently reflecting a faster elimination of HCP from the blood. By substantially increasing the HCP dose, higher blood concentrations were obtained in adult than less the 16-day-old mice; in spite of this, PNS myelin changes occurred only in the latter. Thus, by observing the HCP effect on the transitional region, where CNS and PNS directly meet, it is concluded that CNS of both suckling and adult mice is more severely effected by HCP than PNS, and that the reaction of the PNS myelin is age-dependent during the period of myelinogenesis; it is particularly vulnerable to a cytotoxic edema inducing substance.", "contents": "Studies on hexachlorophene-induced myelin lesions in the trigeminal root transitional region in developing and adult mice. Hexachlorophene (HCP)-induced intramyelinic vacuolation was studied in the transitional region of the trigeminal root of suckling and adult mice. HCP produced an extensive vacuolation in the central compartment of the region in both suckling and adult mice, while in the peripheral compartment myelin lesions were only seen in mice less than 16 days of age. Gas chromatographic measurements showed that in suckling mice the blood concentration of HCP decreased with age, apparently reflecting a faster elimination of HCP from the blood. By substantially increasing the HCP dose, higher blood concentrations were obtained in adult than less the 16-day-old mice; in spite of this, PNS myelin changes occurred only in the latter. Thus, by observing the HCP effect on the transitional region, where CNS and PNS directly meet, it is concluded that CNS of both suckling and adult mice is more severely effected by HCP than PNS, and that the reaction of the PNS myelin is age-dependent during the period of myelinogenesis; it is particularly vulnerable to a cytotoxic edema inducing substance."}
{"id": "PMID:207075", "title": "Granulocytic sarcoma of the central nervous system: inital presentation of leukemia.", "content": "Granulocytic sarcoma as the presenting feature of leukemia is rare. Although it has been reported in various sites such as the retrobulbar area, mastoid region, iliac bone, and breast, this appears to be the first recorded case presenting as an intracranial tumor.", "contents": "Granulocytic sarcoma of the central nervous system: inital presentation of leukemia. Granulocytic sarcoma as the presenting feature of leukemia is rare. Although it has been reported in various sites such as the retrobulbar area, mastoid region, iliac bone, and breast, this appears to be the first recorded case presenting as an intracranial tumor."}
{"id": "PMID:207076", "title": "The Poland anomalad: a clinical and cytogenetic study of seven cases.", "content": "Seven patients with Poland anomalad, 6 males and one female, are reported. Four were affected on the right and 3 on the left side. The clinical, radiological and cytogenetic findings in these cases are discussed. In all the patients the nipples were asymmetric, the one on the affected side was sometimes set higher or lower than the one on the normal side, in relation to the extent of the muscle defect. One patient had coloboma of the iris. There was a greater variability of the defect of the upper extremity and especially of the ipsilateral hand than of the muscle anomaly. The hand seemed almost normal in 3 cases but these cases seem to represent the variability of the malformation. All cases were sporadic. Delivery was complicated in 4/7 and one patient had a twin brother with myelomeningocele.", "contents": "The Poland anomalad: a clinical and cytogenetic study of seven cases. Seven patients with Poland anomalad, 6 males and one female, are reported. Four were affected on the right and 3 on the left side. The clinical, radiological and cytogenetic findings in these cases are discussed. In all the patients the nipples were asymmetric, the one on the affected side was sometimes set higher or lower than the one on the normal side, in relation to the extent of the muscle defect. One patient had coloboma of the iris. There was a greater variability of the defect of the upper extremity and especially of the ipsilateral hand than of the muscle anomaly. The hand seemed almost normal in 3 cases but these cases seem to represent the variability of the malformation. All cases were sporadic. Delivery was complicated in 4/7 and one patient had a twin brother with myelomeningocele."}
{"id": "PMID:207077", "title": "Congenital and acquired cytomegalovirus infections. Virological and clinical studies on a Swedish infant population.", "content": "The study included two clinical materials. First, the frequency of cytomegalovirus and its clinical significance were studied among 661 Swedish children under one year of age admitted to a paediatric hospital. Before the age of one week 4/326 (1%) children excreted virus. At one month the frequency had risen to 6/52 (12%) and after this age the frequency was constant around 20--25%. Sixty per cent of infants born to immigrants were infected after one month of age. One of the four congenitally infected children had symptoms at birth followed by neurological sequelae. The majority of the infections acquired at birth or in early infancy seemed to be subclinical and without sequelae. Second, a retrospective investigation of 18 695 children born during a six-year period was performed. Two cases of virologically confirmed congenital cytomegalic inclusion disease was found. Regarding seven microcephalic patients in the retrospective study congenital CMV-infection could be excluded in four cases. In the remaining three cases the data did not permit any conclusions regarding the etiology.", "contents": "Congenital and acquired cytomegalovirus infections. Virological and clinical studies on a Swedish infant population. The study included two clinical materials. First, the frequency of cytomegalovirus and its clinical significance were studied among 661 Swedish children under one year of age admitted to a paediatric hospital. Before the age of one week 4/326 (1%) children excreted virus. At one month the frequency had risen to 6/52 (12%) and after this age the frequency was constant around 20--25%. Sixty per cent of infants born to immigrants were infected after one month of age. One of the four congenitally infected children had symptoms at birth followed by neurological sequelae. The majority of the infections acquired at birth or in early infancy seemed to be subclinical and without sequelae. Second, a retrospective investigation of 18 695 children born during a six-year period was performed. Two cases of virologically confirmed congenital cytomegalic inclusion disease was found. Regarding seven microcephalic patients in the retrospective study congenital CMV-infection could be excluded in four cases. In the remaining three cases the data did not permit any conclusions regarding the etiology."}
{"id": "PMID:207078", "title": "Urinary cyclic AMP in infants admitted to a neonatal intensive care unit.", "content": "The urinary excretion of cyclic AMP was studied during the first 3 days of life in 46 randomly selected infants admitted to a neonatal intensive care unit. The data were compared with those of normal newborn infants. Urinary cyclic AMP concentrations were significantly correlated with gestational age (all patients), and with birth weight (all patients except infants of diabetic mothers (IDMs)). The urinary cyclic AMP/creatine ratio increased from day 1 to day 3 in normal newborns and in IDMs, and tended to increase also in small-for-gestational age (SGA), low birth weight (LBW), and sick, term infants, although the changes in the latter groups were not statistically significant. Four infants studied with parallel determinations showed increased cyclic AMP/creatinine ratio from day 1 to day 3 both in plasma and urine. All urinary cyclic AMP/creatine ratios were lower than the corresponding ratios found in plasma. In LBW infants, there was an inverse relationship between urinary cyclic AMP and serum calcium. In IDMs a positive correlation was observed between urinary cyclic AMP and blood glucose concentration. In conclusion, the excretion of cyclic AMP in sick newborn infants is influenced by the following factors: gestational age, postnatal age, birth weight, and derangements of serum calcium and blood glucose concentrations.", "contents": "Urinary cyclic AMP in infants admitted to a neonatal intensive care unit. The urinary excretion of cyclic AMP was studied during the first 3 days of life in 46 randomly selected infants admitted to a neonatal intensive care unit. The data were compared with those of normal newborn infants. Urinary cyclic AMP concentrations were significantly correlated with gestational age (all patients), and with birth weight (all patients except infants of diabetic mothers (IDMs)). The urinary cyclic AMP/creatine ratio increased from day 1 to day 3 in normal newborns and in IDMs, and tended to increase also in small-for-gestational age (SGA), low birth weight (LBW), and sick, term infants, although the changes in the latter groups were not statistically significant. Four infants studied with parallel determinations showed increased cyclic AMP/creatinine ratio from day 1 to day 3 both in plasma and urine. All urinary cyclic AMP/creatine ratios were lower than the corresponding ratios found in plasma. In LBW infants, there was an inverse relationship between urinary cyclic AMP and serum calcium. In IDMs a positive correlation was observed between urinary cyclic AMP and blood glucose concentration. In conclusion, the excretion of cyclic AMP in sick newborn infants is influenced by the following factors: gestational age, postnatal age, birth weight, and derangements of serum calcium and blood glucose concentrations."}
{"id": "PMID:207083", "title": "Tension and cyclic GMP changes in potassium depolarized rabbit colon muscle.", "content": "Potassium depolarization of rabbit colon muscle elicited a contraction consisting of 2 distinct phases, an initial rapid phasic contraction and a tonic contracture. The tonic contraction was, in contrast to the phasic contraction, dependent on the extracellular calcium for its development. There was a correlation between the tension development and the increase of the cyclic GMP level in the K+-depolarized muscle. Experimental conditions which abolished the tonic contracture, viz glucose omission and treatment with Ca2+-antagonists (verapamil, SKF 525A) also inhibited the cyclic GMP response. The changes of the cyclic GMP levels were Ca2+-dependent. K+-ions also changes the cyclic AMP content an effect which was atropine sensitive. From the experimental data obtained in this investigation we suggest that the co-variation of the tension and the cyclic GMP level in the depolarized colon muscle might depend on oscillations in a common intracellular factor, probably Ca2+.", "contents": "Tension and cyclic GMP changes in potassium depolarized rabbit colon muscle. Potassium depolarization of rabbit colon muscle elicited a contraction consisting of 2 distinct phases, an initial rapid phasic contraction and a tonic contracture. The tonic contraction was, in contrast to the phasic contraction, dependent on the extracellular calcium for its development. There was a correlation between the tension development and the increase of the cyclic GMP level in the K+-depolarized muscle. Experimental conditions which abolished the tonic contracture, viz glucose omission and treatment with Ca2+-antagonists (verapamil, SKF 525A) also inhibited the cyclic GMP response. The changes of the cyclic GMP levels were Ca2+-dependent. K+-ions also changes the cyclic AMP content an effect which was atropine sensitive. From the experimental data obtained in this investigation we suggest that the co-variation of the tension and the cyclic GMP level in the depolarized colon muscle might depend on oscillations in a common intracellular factor, probably Ca2+."}
{"id": "PMID:207084", "title": "Fluid transfer from skeletal muscle to blood during hemorrhage. Importance of beta adrenergic vascular mechanisms.", "content": "Vascular reactions in the cat lower leg in response to short-term (10 min) hemorrhagic hypotension (approximately 80 mmHg) were studied before and after regional blockade of the beta-adrenoceptors. In the muscle region with intact beta-adrenoceptors, hemorrhage raised vascular resistance by about 80% and caused a dilatation of the precapillary sphincters, the latter effect evidenced in terms of a 35% increase of the capillary filtration coefficient. Concomitantly, an absorption of extravascular fluid to the blood stream occurred, a process tending to compensate for the reduction of intravascular fluid volume. After regional beta-blockade there was quite a marked augmentation of the hemorrhage induced increase of vascular resistance whereas the inhibition of precapillary sphincter tone and the transcapillary fluid absorption were almost abolished. These observations indicate that bleeding is associated with a significant beta-adrenergic dilator influence in both the resistance vessels and precapillary sphincters of skeletal muscle and that the beta-dilator mechanism may be essential for the important, compensatory fluid gain from the extravascular to the intravascular space during hemorrhage. The observed beta-adrenergic mediation of the net transcapillary fluid absorption could be ascribed to resetting of the pre-/postcapillary resistance ratio, leading to decreased capillary hydrostatic pressure, and to the dilator influence in the precapillary sphincters, leading to an increased number of the patent capillaries available for the transcapillary fluid exchange.", "contents": "Fluid transfer from skeletal muscle to blood during hemorrhage. Importance of beta adrenergic vascular mechanisms. Vascular reactions in the cat lower leg in response to short-term (10 min) hemorrhagic hypotension (approximately 80 mmHg) were studied before and after regional blockade of the beta-adrenoceptors. In the muscle region with intact beta-adrenoceptors, hemorrhage raised vascular resistance by about 80% and caused a dilatation of the precapillary sphincters, the latter effect evidenced in terms of a 35% increase of the capillary filtration coefficient. Concomitantly, an absorption of extravascular fluid to the blood stream occurred, a process tending to compensate for the reduction of intravascular fluid volume. After regional beta-blockade there was quite a marked augmentation of the hemorrhage induced increase of vascular resistance whereas the inhibition of precapillary sphincter tone and the transcapillary fluid absorption were almost abolished. These observations indicate that bleeding is associated with a significant beta-adrenergic dilator influence in both the resistance vessels and precapillary sphincters of skeletal muscle and that the beta-dilator mechanism may be essential for the important, compensatory fluid gain from the extravascular to the intravascular space during hemorrhage. The observed beta-adrenergic mediation of the net transcapillary fluid absorption could be ascribed to resetting of the pre-/postcapillary resistance ratio, leading to decreased capillary hydrostatic pressure, and to the dilator influence in the precapillary sphincters, leading to an increased number of the patent capillaries available for the transcapillary fluid exchange."}
{"id": "PMID:207085", "title": "Vasodilatation and modulation of vasoconstriction in canine subcutaneous adipose tissue caused by activation of beta-adrenoceptors.", "content": "The present experiments were undertaken to study the balance between vascular alpha- and beta-adrenoceptors in canine subcutaneous adipose tissue during sympathetic nerve stimulation and noradrenaline injections. Propranolol potentiated and prolonged the vasoconstrictor response to close i.a. injections of noradrenaline. The vasoconstriction induced by brief nerve stimulation (0.5 to 8 Hz) was, however, unaltered by the beta-adrenoceptor blockade. During prolonged nerve stimulation the vasoconstrictor response was well maintained at 1.5 Hz but at 4 Hz there was a gradual escape. The escape phenomenon at 4 Hz was diminished by propranolol. The beta1-selective antagonist practolol, like propranolol, potentiated and prolonged the vasoconstriction induced by noradrenaline injections and reduced the vasoconstrictor escape during prolonged nerve stimulation at 4 Hz. Furthermore, the vasodilatation induced by noradrenaline injection or nerve stimulation during alpha-adrenoceptor blockade was diminished by practolol. Practolol also blocked the lipolytic response to noradrenaline and nerve stimulation. The beta2-selective antagonist H35/25 blocked the effects of the beta2-selective agonist salbutamol but failed to alter noradrenaline as well as nerve stimulation induced vascular and lipolytic beta-adrenoceptor responses. The present results provide further support for the hypothesis that vascular beta-adrenoceptors in adipose tissue are humoral (noninnervated), preferentially activated by circulating noradrenaline. Moreover, both vascular and lipolytic beta-adrenoceptors activated by noradrenaline in adipose tissue are best classified as beta1-adrenoceptors.", "contents": "Vasodilatation and modulation of vasoconstriction in canine subcutaneous adipose tissue caused by activation of beta-adrenoceptors. The present experiments were undertaken to study the balance between vascular alpha- and beta-adrenoceptors in canine subcutaneous adipose tissue during sympathetic nerve stimulation and noradrenaline injections. Propranolol potentiated and prolonged the vasoconstrictor response to close i.a. injections of noradrenaline. The vasoconstriction induced by brief nerve stimulation (0.5 to 8 Hz) was, however, unaltered by the beta-adrenoceptor blockade. During prolonged nerve stimulation the vasoconstrictor response was well maintained at 1.5 Hz but at 4 Hz there was a gradual escape. The escape phenomenon at 4 Hz was diminished by propranolol. The beta1-selective antagonist practolol, like propranolol, potentiated and prolonged the vasoconstriction induced by noradrenaline injections and reduced the vasoconstrictor escape during prolonged nerve stimulation at 4 Hz. Furthermore, the vasodilatation induced by noradrenaline injection or nerve stimulation during alpha-adrenoceptor blockade was diminished by practolol. Practolol also blocked the lipolytic response to noradrenaline and nerve stimulation. The beta2-selective antagonist H35/25 blocked the effects of the beta2-selective agonist salbutamol but failed to alter noradrenaline as well as nerve stimulation induced vascular and lipolytic beta-adrenoceptor responses. The present results provide further support for the hypothesis that vascular beta-adrenoceptors in adipose tissue are humoral (noninnervated), preferentially activated by circulating noradrenaline. Moreover, both vascular and lipolytic beta-adrenoceptors activated by noradrenaline in adipose tissue are best classified as beta1-adrenoceptors."}
{"id": "PMID:207081", "title": "Central action of catecholamines on the cardiovascular system in rats.", "content": "Central action of catecholamines on the cardiovascular system in rats. Acta Physiol Pol., 1978, 29 (2): 123--130. It was demonstrated that noradrenaline, adrenaline, dopamine and isoproterenol as well as normethanephrine administered into the lateral ventricle of the rat brain, under urethane anaesthesia, caused significant changes in arterial blood pressure. This action is due to stimulation of central adrenergic receptors. Arterial blood pressure rise after intraventricular administration of noradrenaline is caused by activation of the renin-angiotensin system in the periphery. The results of these experiments point to a role of central catecholamines in functional regulation ofthe cardiovascular system.", "contents": "Central action of catecholamines on the cardiovascular system in rats. Central action of catecholamines on the cardiovascular system in rats. Acta Physiol Pol., 1978, 29 (2): 123--130. It was demonstrated that noradrenaline, adrenaline, dopamine and isoproterenol as well as normethanephrine administered into the lateral ventricle of the rat brain, under urethane anaesthesia, caused significant changes in arterial blood pressure. This action is due to stimulation of central adrenergic receptors. Arterial blood pressure rise after intraventricular administration of noradrenaline is caused by activation of the renin-angiotensin system in the periphery. The results of these experiments point to a role of central catecholamines in functional regulation ofthe cardiovascular system."}
{"id": "PMID:207082", "title": "The effects of vitamin D on the rat kidney metabolism under conditions of experimental hypercalcemia.", "content": "The effects of vitamin D3 on rat kideney metabolism under conditions of experimental hypercalcemia. Acta Physiol. Pol., 1978, 29 (2) 153--159. The effect of vitamin D3 on renal gluconeogenesis processes was studied in the rat. The performed estimations of gluconeogenesis rate from malate and lactate demonstrated significant increases of glucose formation rate when kidney cortex slices of the vitamin D3 treated animals were analyzed. Further studies on the mechanism of the observed phenomenon were performed using kidney cell fractionation procedure and fluorometric estimation of the concentration of selected gluconeogenetic metabolites. Significant increases of phosphoenolpyruvate concentration in the cytosol fraction and citrate concentration in the mitochondrial fraction were observed. Comparison of the described action of vitamin D3 on gluconeogenesis and the effect of parathyriod hormone, as known from the literature suggests similar mechanism of both factor actions. A possibility of vitamin D3 action through the increase in intracellular calcium has been discussed.", "contents": "The effects of vitamin D on the rat kidney metabolism under conditions of experimental hypercalcemia. The effects of vitamin D3 on rat kideney metabolism under conditions of experimental hypercalcemia. Acta Physiol. Pol., 1978, 29 (2) 153--159. The effect of vitamin D3 on renal gluconeogenesis processes was studied in the rat. The performed estimations of gluconeogenesis rate from malate and lactate demonstrated significant increases of glucose formation rate when kidney cortex slices of the vitamin D3 treated animals were analyzed. Further studies on the mechanism of the observed phenomenon were performed using kidney cell fractionation procedure and fluorometric estimation of the concentration of selected gluconeogenetic metabolites. Significant increases of phosphoenolpyruvate concentration in the cytosol fraction and citrate concentration in the mitochondrial fraction were observed. Comparison of the described action of vitamin D3 on gluconeogenesis and the effect of parathyriod hormone, as known from the literature suggests similar mechanism of both factor actions. A possibility of vitamin D3 action through the increase in intracellular calcium has been discussed."}
{"id": "PMID:207086", "title": "Progressing stroke. Angiographic aspects.", "content": "Progressing strokes were noted in 17 of 256 patients who underwent surgery for atheromatous disease involving the internal carotid artery. This disorder was characterized by an active increase in the neurologic deficit during an 18- to 24-hour period. Although angiographic findings were neither specific for this type of cerebrovascular disease nor uniformly present, the angiography did indicate that not only embolization of the cerebral leptomeningeal conducting vessels but also collaterization through them was a pertinent mechanism.", "contents": "Progressing stroke. Angiographic aspects. Progressing strokes were noted in 17 of 256 patients who underwent surgery for atheromatous disease involving the internal carotid artery. This disorder was characterized by an active increase in the neurologic deficit during an 18- to 24-hour period. Although angiographic findings were neither specific for this type of cerebrovascular disease nor uniformly present, the angiography did indicate that not only embolization of the cerebral leptomeningeal conducting vessels but also collaterization through them was a pertinent mechanism."}
{"id": "PMID:207087", "title": "Isotopic and angiographic determination of cerebral blood flow. A correlation in patients with cerebral death.", "content": "Total cerebral angiography has been performed on five patients who were demonstrated to have a cerebral circulatory deficit by the bedside isotope flow determination. In all five instances cerebral angiography confirmed the results of the isotope examination.", "contents": "Isotopic and angiographic determination of cerebral blood flow. A correlation in patients with cerebral death. Total cerebral angiography has been performed on five patients who were demonstrated to have a cerebral circulatory deficit by the bedside isotope flow determination. In all five instances cerebral angiography confirmed the results of the isotope examination."}
{"id": "PMID:207088", "title": "Ischemic chiasmal syndrome.", "content": "Twenty-two patients with ischemic chiasmal syndrome (ICS) have been examined by means of magnification angiography and polytomographic encephalography. The causes of ICS may be divided into 5 categories: (1) mechanical compression of the chiasm by ectatic redundant anterior cerebral arteries, (2) atherosclerotic vascular occlusions, (3) optochiasmal arachnoidal fibrosis, (4) various forms of arteritis especially giant cell (cranial) arteritis, and (5) post-partum pituitary necrosis associated with ICS. The most common cause of ICS appears to be optochiasmal arachnoiditis which occasionally developed some time after a craniotomy and radiation therapy for pituitary or other juxta-sellar tumors; similar fibrotic change may develop following steroid treatment of granulomatous lesions.", "contents": "Ischemic chiasmal syndrome. Twenty-two patients with ischemic chiasmal syndrome (ICS) have been examined by means of magnification angiography and polytomographic encephalography. The causes of ICS may be divided into 5 categories: (1) mechanical compression of the chiasm by ectatic redundant anterior cerebral arteries, (2) atherosclerotic vascular occlusions, (3) optochiasmal arachnoidal fibrosis, (4) various forms of arteritis especially giant cell (cranial) arteritis, and (5) post-partum pituitary necrosis associated with ICS. The most common cause of ICS appears to be optochiasmal arachnoiditis which occasionally developed some time after a craniotomy and radiation therapy for pituitary or other juxta-sellar tumors; similar fibrotic change may develop following steroid treatment of granulomatous lesions."}
{"id": "PMID:207089", "title": "Effect of cardiac arrest on cerebral circulation. An experimental investigation.", "content": "The effect of 2 to 15 min of cardiac arrest on cerebral circulation was investigated in dogs and Rhesus monkeys. When circulatory arrest lasted longer than 5 minutes, angiographic changes of the no-reflow phenomenon were observed between 3 and 4 h after resuscitation in dogs but not in monkeys. These findings were (1) marked prolongation of the arterial phase in both intracranial and extracranial arteries; followed by (2) occasional evidence of dilatation of the proximal intracranial arteries with non-filling of the distal intracranial arteries; and (3) faint demonstration of the venous phase. Carbon black perfusion results were (1) diffuse lack of perfusion at the arteriolar-capillary level and (2) multifocal areas of filling defects. Regional cortical blood flow measurement in monkeys disclosed a significant decrease in flow starting from 3 h after re-establishment of circulation for those in which longer than 5 min of arrest was induced.", "contents": "Effect of cardiac arrest on cerebral circulation. An experimental investigation. The effect of 2 to 15 min of cardiac arrest on cerebral circulation was investigated in dogs and Rhesus monkeys. When circulatory arrest lasted longer than 5 minutes, angiographic changes of the no-reflow phenomenon were observed between 3 and 4 h after resuscitation in dogs but not in monkeys. These findings were (1) marked prolongation of the arterial phase in both intracranial and extracranial arteries; followed by (2) occasional evidence of dilatation of the proximal intracranial arteries with non-filling of the distal intracranial arteries; and (3) faint demonstration of the venous phase. Carbon black perfusion results were (1) diffuse lack of perfusion at the arteriolar-capillary level and (2) multifocal areas of filling defects. Regional cortical blood flow measurement in monkeys disclosed a significant decrease in flow starting from 3 h after re-establishment of circulation for those in which longer than 5 min of arrest was induced."}
{"id": "PMID:207090", "title": "Angiographic findings in intraventricular hemorrhage in newborn infants.", "content": "The present investigation indicates that early filling of deep veins is common in newborn infants on angiography. The characteristic findings of the intraventricular hemorrhage in newborn infants are (1) hydrocephalus and (2) prolonged stasis of contrast medium in choroid plexus in the lateral ventricles.", "contents": "Angiographic findings in intraventricular hemorrhage in newborn infants. The present investigation indicates that early filling of deep veins is common in newborn infants on angiography. The characteristic findings of the intraventricular hemorrhage in newborn infants are (1) hydrocephalus and (2) prolonged stasis of contrast medium in choroid plexus in the lateral ventricles."}
{"id": "PMID:207091", "title": "[Embolization by femoral catheterization of tumors supplied by the external carotid artery. 40 cases].", "content": "Experiences from therapeutic embolization by way of superselective catheterization of the external carotid artery, in 40 cases of cranio-cerebral, maxillo-facial and cervical tumours are reported. Using Spongel, embolization offered definite advantages compared to simple arterial ligation: it is easily performed as a supplementary procedure to diagnostic superselective angiography; a meticulous technique will provide superselective arterial occlusion with obstruction of vessels down to the precapillary size (diameter 150 to 200 mu). Embolization is advocated as a preoperative measure in meningeomas (particularly at the skull base), naso-pharyngeal angiofibromas, intracranial and cervical chemodectomas, in which cases profound bleeding during surgery may be expected and as a palliative measure in cases where surgery and radiation therapy fail to control recurrence of a tumour.", "contents": "[Embolization by femoral catheterization of tumors supplied by the external carotid artery. 40 cases]. Experiences from therapeutic embolization by way of superselective catheterization of the external carotid artery, in 40 cases of cranio-cerebral, maxillo-facial and cervical tumours are reported. Using Spongel, embolization offered definite advantages compared to simple arterial ligation: it is easily performed as a supplementary procedure to diagnostic superselective angiography; a meticulous technique will provide superselective arterial occlusion with obstruction of vessels down to the precapillary size (diameter 150 to 200 mu). Embolization is advocated as a preoperative measure in meningeomas (particularly at the skull base), naso-pharyngeal angiofibromas, intracranial and cervical chemodectomas, in which cases profound bleeding during surgery may be expected and as a palliative measure in cases where surgery and radiation therapy fail to control recurrence of a tumour."}
{"id": "PMID:207093", "title": "Carotid angiography in cerebral metastases.", "content": "Carotid angiography was performed in 138 cases of brain metastases. No pathologic vascularity was found in 55 per cent, pathologic arterial phase in 10 per cent, capillary phase in 14 per cent and pathologic venous phase in 12 per cent. In six cases, pathologic vascularity was found in all three phases; five of these were hypernephromas.", "contents": "Carotid angiography in cerebral metastases. Carotid angiography was performed in 138 cases of brain metastases. No pathologic vascularity was found in 55 per cent, pathologic arterial phase in 10 per cent, capillary phase in 14 per cent and pathologic venous phase in 12 per cent. In six cases, pathologic vascularity was found in all three phases; five of these were hypernephromas."}
{"id": "PMID:207096", "title": "Medullary arteries in cerebral neoplasms.", "content": "In cerebral neoplasms, the visibility of long segments of the medullary arteries indicates white matter involvement by infiltrative or compressive disturbances. Relating the mass effect to the position of the medullary arteries should allow for differentiating a primary from a secondary avascular neoplasm. When the neoplasm is vascular, the presence of neovascularity with the medullary arteries is likely to signify a high degree of anaplasia.", "contents": "Medullary arteries in cerebral neoplasms. In cerebral neoplasms, the visibility of long segments of the medullary arteries indicates white matter involvement by infiltrative or compressive disturbances. Relating the mass effect to the position of the medullary arteries should allow for differentiating a primary from a secondary avascular neoplasm. When the neoplasm is vascular, the presence of neovascularity with the medullary arteries is likely to signify a high degree of anaplasia."}
{"id": "PMID:207097", "title": "Neuroparallelogram. A cerebral angiographic system allowing for isocentric magnification.", "content": "The Neuroparallelogram, a radiographic system with an opposing tube-serial film changer provides for isoentric 2:1 magnification, stero radiography, a.p. or p.a. projections, more accurately positioned bi-plane angiography and the capacity for angiotomography. Angiographic examinations are expedited not only by the ease of set-up for different projections, but also by the capacity to accommodate for head rotation without repositioning the patient. The tube and film changer can be uncoupled so that routine films may be obtained. The improved detail of magnification radiography and the simplicity of positioning can also be used to perform routine skull radiography.", "contents": "Neuroparallelogram. A cerebral angiographic system allowing for isocentric magnification. The Neuroparallelogram, a radiographic system with an opposing tube-serial film changer provides for isoentric 2:1 magnification, stero radiography, a.p. or p.a. projections, more accurately positioned bi-plane angiography and the capacity for angiotomography. Angiographic examinations are expedited not only by the ease of set-up for different projections, but also by the capacity to accommodate for head rotation without repositioning the patient. The tube and film changer can be uncoupled so that routine films may be obtained. The improved detail of magnification radiography and the simplicity of positioning can also be used to perform routine skull radiography."}
{"id": "PMID:207098", "title": "Non-filling of the subependymal veins of the lateral ventricles.", "content": "Four cases of non-filling of the subependymal veins of the lateral ventricles and internal cerebral vein at carotid angiography are reported. The patients were all children ranging in age from 4 months to 2 years and had a variety of neurologic conditions. Several hypotheses are suggested as to the possible pathogenesis of these findings.", "contents": "Non-filling of the subependymal veins of the lateral ventricles. Four cases of non-filling of the subependymal veins of the lateral ventricles and internal cerebral vein at carotid angiography are reported. The patients were all children ranging in age from 4 months to 2 years and had a variety of neurologic conditions. Several hypotheses are suggested as to the possible pathogenesis of these findings."}
{"id": "PMID:207099", "title": "Etiology of moya moya disease acquired or congenital.", "content": "Nine cases of Moya Moya disease collected since 1968 are presented. The absence of inflammatory signs and the high percentage of congenital malformations is emphasized. However, despite the post-mortem findings in one of the cases, no etiologic factor has been conclusively demonstrated.", "contents": "Etiology of moya moya disease acquired or congenital. Nine cases of Moya Moya disease collected since 1968 are presented. The absence of inflammatory signs and the high percentage of congenital malformations is emphasized. However, despite the post-mortem findings in one of the cases, no etiologic factor has been conclusively demonstrated."}
{"id": "PMID:207100", "title": "Arteriovenous malformation of the vein of Galen.", "content": "Vein of Galen aneurysm may be caused by a spectrum of abnormal arteriovenous connections ranging from extensive malformations involving the tentorial dura and upper brain stem vessels to the rarer condition of a simple end to end fistulous connection. The diagnosis of the latter condition of a simple arteriovenous fistula is important because it may be effectively managed by surgical interruption of the feeding fistulous vessels. Two cases with the direct fistulous connections are presented.", "contents": "Arteriovenous malformation of the vein of Galen. Vein of Galen aneurysm may be caused by a spectrum of abnormal arteriovenous connections ranging from extensive malformations involving the tentorial dura and upper brain stem vessels to the rarer condition of a simple end to end fistulous connection. The diagnosis of the latter condition of a simple arteriovenous fistula is important because it may be effectively managed by surgical interruption of the feeding fistulous vessels. Two cases with the direct fistulous connections are presented."}
{"id": "PMID:207101", "title": "Application of the 105 mm camera in cerebral angiography.", "content": "The 105 mm film camera is being increasingly used with the newer high resolution dual mode image intensifier in various radiologic procedures. Its use in various intracranial and extracranial neurovascular procedures has been evaluated. An attempt is made to compare these results with those obtained with conventional film changers. Also considered are the saving in both time and radiation to both the patient and radiologist.", "contents": "Application of the 105 mm camera in cerebral angiography. The 105 mm film camera is being increasingly used with the newer high resolution dual mode image intensifier in various radiologic procedures. Its use in various intracranial and extracranial neurovascular procedures has been evaluated. An attempt is made to compare these results with those obtained with conventional film changers. Also considered are the saving in both time and radiation to both the patient and radiologist."}
{"id": "PMID:207102", "title": "Regional blood flow measurement in extra-intracranial anastomoses for cerebral ischemia. Methodologic aspects.", "content": "The value of regional cerebral blood flow measurement for the microneurosurgical treatment of cerebral ischemia is outlined. Preoperatively, this method is of great value for the selection of suitable candidates for this operation. Postoperatively, the effect of the extraintracranial arterial bypass on the ischemic brain may be quantitatively assessed. The practical management of flow measurements in these patients is discussed.", "contents": "Regional blood flow measurement in extra-intracranial anastomoses for cerebral ischemia. Methodologic aspects. The value of regional cerebral blood flow measurement for the microneurosurgical treatment of cerebral ischemia is outlined. Preoperatively, this method is of great value for the selection of suitable candidates for this operation. Postoperatively, the effect of the extraintracranial arterial bypass on the ischemic brain may be quantitatively assessed. The practical management of flow measurements in these patients is discussed."}
{"id": "PMID:207103", "title": "Abnormal cerebral vasomotor response in patients with brain tumors.", "content": "In 37 patients with intracranial tumros, regional cerebral blood flow was measured. The typical abnormalities are described and an attempt is made to correlate the blood flow with the histologic type of tumor. Moreover, the deranged cerebral vasomotor responses are demonstrated when the flow is measured during functional tests. The practical value of the method in patients with brain tumors is discussed.", "contents": "Abnormal cerebral vasomotor response in patients with brain tumors. In 37 patients with intracranial tumros, regional cerebral blood flow was measured. The typical abnormalities are described and an attempt is made to correlate the blood flow with the histologic type of tumor. Moreover, the deranged cerebral vasomotor responses are demonstrated when the flow is measured during functional tests. The practical value of the method in patients with brain tumors is discussed."}
{"id": "PMID:207104", "title": "Post mortem investigation of the vertebrabasilar system.", "content": "The shape, origin, termination and number of the main arteries of the vertebrobasilar system have been analysed in 30 anatomic specimens by dissection of the injected vessels and by radiography. Five projections are described for identifying the different regions of the brain stem and cerebellum through the appearance of the arteries. A technique is proposed for obtaining a 'true' a.p. view of the vessels in vertebral angiography in patients.", "contents": "Post mortem investigation of the vertebrabasilar system. The shape, origin, termination and number of the main arteries of the vertebrobasilar system have been analysed in 30 anatomic specimens by dissection of the injected vessels and by radiography. Five projections are described for identifying the different regions of the brain stem and cerebellum through the appearance of the arteries. A technique is proposed for obtaining a 'true' a.p. view of the vessels in vertebral angiography in patients."}
{"id": "PMID:207105", "title": "Lysis of thrombus in internal carotid artery in the neck. Report of a case.", "content": "A case report is presented demonstrating spontaneous lysis of clot in the internal carotid artery in the neck with surgical and angiographic documentation. The possible factors promoting thrombus formation and lysis are discussed. Spontaneous lysis of a carotid thrombus occurred in 72 hours.", "contents": "Lysis of thrombus in internal carotid artery in the neck. Report of a case. A case report is presented demonstrating spontaneous lysis of clot in the internal carotid artery in the neck with surgical and angiographic documentation. The possible factors promoting thrombus formation and lysis are discussed. Spontaneous lysis of a carotid thrombus occurred in 72 hours."}
{"id": "PMID:207106", "title": "Orbital phlebography and cavernography in intra-cranial lesions.", "content": "Orbital phlebography has gained increasing importance in the evaluation of otologic and intracranial pathology. The practical use of this method in vascular and neoplastic lesions in the middle cranial fossa, as well as its probable value in cerebello-pontine angle tumours is reported.", "contents": "Orbital phlebography and cavernography in intra-cranial lesions. Orbital phlebography has gained increasing importance in the evaluation of otologic and intracranial pathology. The practical use of this method in vascular and neoplastic lesions in the middle cranial fossa, as well as its probable value in cerebello-pontine angle tumours is reported."}
{"id": "PMID:207107", "title": "Capillary phase in angiography.", "content": "The capillary phase is discussed on the basis of primary serial magnification and subtraction. It is suggested that the term 'intermediate phase' better expresses the angiographic appearance in between the arterial and venous phases than the term 'capillary phase'. The intermediate phase is further divided into the precapillary, capillary and postcapillary subphases and anatomic correlations are discussed. Some physiologic and pathologic aspects of the intermediate phase are considered.", "contents": "Capillary phase in angiography. The capillary phase is discussed on the basis of primary serial magnification and subtraction. It is suggested that the term 'intermediate phase' better expresses the angiographic appearance in between the arterial and venous phases than the term 'capillary phase'. The intermediate phase is further divided into the precapillary, capillary and postcapillary subphases and anatomic correlations are discussed. Some physiologic and pathologic aspects of the intermediate phase are considered."}
{"id": "PMID:207108", "title": "Serial magnification angiography under hypocapnia and hypertension.", "content": "Serial magnification angiography under hypocapnia and hypertension was performed in 200 cases of cerebral tumours and cerebrovascular lesions. The advantages over conventional angiography are evident; the extent of a tumour is easier to determine as well as in most cases the nature of the mass lesion.", "contents": "Serial magnification angiography under hypocapnia and hypertension. Serial magnification angiography under hypocapnia and hypertension was performed in 200 cases of cerebral tumours and cerebrovascular lesions. The advantages over conventional angiography are evident; the extent of a tumour is easier to determine as well as in most cases the nature of the mass lesion."}
{"id": "PMID:207109", "title": "Catheter technique for encephalography.", "content": "A catheter technique for encephalography utilizing a polyethylene catheter is described. The advantages are principally that it reduces the possibility of needle displacement during examination and thus the danger of extra-arachnoid injection of air.", "contents": "Catheter technique for encephalography. A catheter technique for encephalography utilizing a polyethylene catheter is described. The advantages are principally that it reduces the possibility of needle displacement during examination and thus the danger of extra-arachnoid injection of air."}
{"id": "PMID:207111", "title": "Hypocycloid tomography in encephalography to demonstrate deep hemorrhage of the brain.", "content": "Five cases of spontaneous deep brain hemorrhage have been presented. Two hemorrhages occurred above the tentorium and three below. The advantages of encephalography combined with tomography in diagnosing and following patients with deep brain hemorrhage are demonstrated in each case.", "contents": "Hypocycloid tomography in encephalography to demonstrate deep hemorrhage of the brain. Five cases of spontaneous deep brain hemorrhage have been presented. Two hemorrhages occurred above the tentorium and three below. The advantages of encephalography combined with tomography in diagnosing and following patients with deep brain hemorrhage are demonstrated in each case."}
{"id": "PMID:207113", "title": "Secondary empty sella syndrome.", "content": "Etiology and pathogenesis of empty cella syndrome remains undetermined in some cases (primary or idiopathic type), while in others it is related to treatment of pituitary and parasellar disease (secondary type). Ten patients with empty sellae, secondary to treatment of pituitary adenomas (five cases), granulomas (three cases), craniopharyngioma (one case), and optic glioma (one case) are presented. Pathogenesis of empty sella is discussed and the importance of neuroradiologic evaluation of this syndrome is stressed.", "contents": "Secondary empty sella syndrome. Etiology and pathogenesis of empty cella syndrome remains undetermined in some cases (primary or idiopathic type), while in others it is related to treatment of pituitary and parasellar disease (secondary type). Ten patients with empty sellae, secondary to treatment of pituitary adenomas (five cases), granulomas (three cases), craniopharyngioma (one case), and optic glioma (one case) are presented. Pathogenesis of empty sella is discussed and the importance of neuroradiologic evaluation of this syndrome is stressed."}
{"id": "PMID:207114", "title": "[Prolactin-secreting adenomas. Radiologic signs].", "content": "The sellar and tomo-encephalographic changes in pituitary prolactin secreting adenomas are described on the base of 75 cases detected within a period of 2 years. In the diagnosis of smaller adenomas in which the sellar findings may be questionable, the value of fractionated encephalography is emphasized, and especially of frontal tomograms, in order to demonstrate a lateral bulging of the sellar diaphragm and a shift of the pituitary stalk to the opposite side.", "contents": "[Prolactin-secreting adenomas. Radiologic signs]. The sellar and tomo-encephalographic changes in pituitary prolactin secreting adenomas are described on the base of 75 cases detected within a period of 2 years. In the diagnosis of smaller adenomas in which the sellar findings may be questionable, the value of fractionated encephalography is emphasized, and especially of frontal tomograms, in order to demonstrate a lateral bulging of the sellar diaphragm and a shift of the pituitary stalk to the opposite side."}
{"id": "PMID:207115", "title": "Encephalography using supra-occipital tapping of the cisterna magna.", "content": "A report is given of the results of supra-occipital tapping of the cisterna magna and dynamic encephalography by that route. In 72 patients with cranial hypertension this encephalography was well tolerated. Supra-occipital tapping is less dangerous than suboccipital puncture as regards the possibility of injury to the medulla. In 38 cases, the method led immediately to the diagnosis of herniation of the tonsils.", "contents": "Encephalography using supra-occipital tapping of the cisterna magna. A report is given of the results of supra-occipital tapping of the cisterna magna and dynamic encephalography by that route. In 72 patients with cranial hypertension this encephalography was well tolerated. Supra-occipital tapping is less dangerous than suboccipital puncture as regards the possibility of injury to the medulla. In 38 cases, the method led immediately to the diagnosis of herniation of the tonsils."}
{"id": "PMID:207116", "title": "[Effect of fractionated pneumoencephalography on intracranial pressure].", "content": "The major changes in clinical condition during and after encephalography may be explained by intracranial pressure variations. If neither intracranial hypertension nor CSF dynamic perturbations exist, minimal complications may be predicted, but in intracranial hypertension immediate deterioration may occur. Despite an apparently good level of tolerance, complications may develop if the compensation phenomena cannot occur: normal pressure hydrocephalus, craniosynostosis. In the cases with good clinical tolerance, minimal changes occur when air injection is administered at a slow rate and with a small volume.", "contents": "[Effect of fractionated pneumoencephalography on intracranial pressure]. The major changes in clinical condition during and after encephalography may be explained by intracranial pressure variations. If neither intracranial hypertension nor CSF dynamic perturbations exist, minimal complications may be predicted, but in intracranial hypertension immediate deterioration may occur. Despite an apparently good level of tolerance, complications may develop if the compensation phenomena cannot occur: normal pressure hydrocephalus, craniosynostosis. In the cases with good clinical tolerance, minimal changes occur when air injection is administered at a slow rate and with a small volume."}
{"id": "PMID:207117", "title": "Spontaneous displacement of air after encephalography.", "content": "In some cases it has been observed that after encephalography air seems to be displaced from one part of the ventricular system to another without movements of the head. This apparently occurs in spite of the law of upward displacement of gases in fluids.", "contents": "Spontaneous displacement of air after encephalography. In some cases it has been observed that after encephalography air seems to be displaced from one part of the ventricular system to another without movements of the head. This apparently occurs in spite of the law of upward displacement of gases in fluids."}
{"id": "PMID:207118", "title": "Ventriculography with water-soluble contrast media.", "content": "Ventriculography with water-soluble contrast media is described. The advantage of subtraction and tomography is discussed. The incidence of side effects and complications of ventriculography with air and Dimer-X are given and compared with data about Conray 60.", "contents": "Ventriculography with water-soluble contrast media. Ventriculography with water-soluble contrast media is described. The advantage of subtraction and tomography is discussed. The incidence of side effects and complications of ventriculography with air and Dimer-X are given and compared with data about Conray 60."}
{"id": "PMID:207119", "title": "The lateral recess of the fourth ventricle examined with a water-soluble contrast medium.", "content": "Difficulties still remain in the routine radiologic examination of the lateral recesses of the fourth ventricle. Ventriculography with the direct introduction of water-soluble contrast medium into the third ventricle has improved the results. The normal anatomic and radiologic appearances and pathologic changes of the lateral recesses are discussed.", "contents": "The lateral recess of the fourth ventricle examined with a water-soluble contrast medium. Difficulties still remain in the routine radiologic examination of the lateral recesses of the fourth ventricle. Ventriculography with the direct introduction of water-soluble contrast medium into the third ventricle has improved the results. The normal anatomic and radiologic appearances and pathologic changes of the lateral recesses are discussed."}
{"id": "PMID:207123", "title": "Central ventriculography in childhood with water-soluble contrast media.", "content": "Central ventriculography was performed by catheterization of the third ventricle or puncture of the anterior horn of the lateral ventricle through the anterior fontanelle. Three different contrast media were compared in 138 cases. Densopax offered the following advantages over Conray and Triyosom 60 MG: Less discomfort to the patient, the procedure may be performed with the patient supine, no danger of embolization, and better demonstration of the aqueduct and fourth ventricle when the ventricular system is greatly dilated.", "contents": "Central ventriculography in childhood with water-soluble contrast media. Central ventriculography was performed by catheterization of the third ventricle or puncture of the anterior horn of the lateral ventricle through the anterior fontanelle. Three different contrast media were compared in 138 cases. Densopax offered the following advantages over Conray and Triyosom 60 MG: Less discomfort to the patient, the procedure may be performed with the patient supine, no danger of embolization, and better demonstration of the aqueduct and fourth ventricle when the ventricular system is greatly dilated."}
{"id": "PMID:207125", "title": "[Intraspinal venous hypertension due to multiple anomalies in the caval system. A major cause of myelopathies].", "content": "Increased venous intraspinal pressure is described as a venous system disease, resulting in numerous unexplained paraplegias and tetraplegias. The chronic venous stasis in the intraspinal plexuses, into which the circulation of the spinal cord is drained, is due to the association of multiple abnormalities (stenoses, compressions, thromboses) on the major pathways of the caval and azygos system. The abnormalities, most of which are not known, are demonstrated by a special procedure, the cavo-spinal phlebography, and some of them are subjected to surgery.", "contents": "[Intraspinal venous hypertension due to multiple anomalies in the caval system. A major cause of myelopathies]. Increased venous intraspinal pressure is described as a venous system disease, resulting in numerous unexplained paraplegias and tetraplegias. The chronic venous stasis in the intraspinal plexuses, into which the circulation of the spinal cord is drained, is due to the association of multiple abnormalities (stenoses, compressions, thromboses) on the major pathways of the caval and azygos system. The abnormalities, most of which are not known, are demonstrated by a special procedure, the cavo-spinal phlebography, and some of them are subjected to surgery."}
{"id": "PMID:207126", "title": "[Cavo-spinal phlebography in myelopathies of venous origin. Application of the method in 115 cases].", "content": "The intraspinal venous stasis, described by ABOULKER as the cause of numerous myelopathies, is due to the addition of multiple venous abnormalities, demonstrated by cavospinal phlebography. The venae cavae and their major affluents and the prespinal system (lumbar and ascending lumbar veins, azygos, hemi-azygos, right superior intercostal and vertebral veins) are explored by catheterization. Cavo-spinal phlebography reveals multiple obstacles and the resulting stasis in the intraspinal plexus.", "contents": "[Cavo-spinal phlebography in myelopathies of venous origin. Application of the method in 115 cases]. The intraspinal venous stasis, described by ABOULKER as the cause of numerous myelopathies, is due to the addition of multiple venous abnormalities, demonstrated by cavospinal phlebography. The venae cavae and their major affluents and the prespinal system (lumbar and ascending lumbar veins, azygos, hemi-azygos, right superior intercostal and vertebral veins) are explored by catheterization. Cavo-spinal phlebography reveals multiple obstacles and the resulting stasis in the intraspinal plexus."}
{"id": "PMID:207127", "title": "[Cavo-spinal phlebography in myelopathies. Stenoses of internal jugular and azygos veins, venous compressions and thromboses].", "content": "Increased intraspinal venous pressure, resulting according to ABOULKER in numerous spastic paraplegias and quadriplegias is due to multiple venous abnormalities demonstrated by cavo-spinal phlebography. The most frequent are stenoses of the internal jugular veins, the left renal, the left iliac veins, the azygos veins and compressions of the innominate venous trunks. These abnormalities cause a permanent stasis in the intraspinal plexuses through excessive supply or insufficient drainage. Out of 80 patients, 60 per cent had at least 2 abnormalities, 38 per cent at least 3 abnormalities.", "contents": "[Cavo-spinal phlebography in myelopathies. Stenoses of internal jugular and azygos veins, venous compressions and thromboses]. Increased intraspinal venous pressure, resulting according to ABOULKER in numerous spastic paraplegias and quadriplegias is due to multiple venous abnormalities demonstrated by cavo-spinal phlebography. The most frequent are stenoses of the internal jugular veins, the left renal, the left iliac veins, the azygos veins and compressions of the innominate venous trunks. These abnormalities cause a permanent stasis in the intraspinal plexuses through excessive supply or insufficient drainage. Out of 80 patients, 60 per cent had at least 2 abnormalities, 38 per cent at least 3 abnormalities."}
{"id": "PMID:207128", "title": "Lumbar tomomyelography with water-soluble contrast medium.", "content": "Myelography supplemented by tomography was routinely carried out in 150 cases. The number of false negative findings was reduced practically to nil. At present, this method is only used in cases with equivocal results at conventional myelography or with poor correlation between clinical symptomatology and myelography. The frequency of side effects in 500 examinations with Dimer-X is unimportant.", "contents": "Lumbar tomomyelography with water-soluble contrast medium. Myelography supplemented by tomography was routinely carried out in 150 cases. The number of false negative findings was reduced practically to nil. At present, this method is only used in cases with equivocal results at conventional myelography or with poor correlation between clinical symptomatology and myelography. The frequency of side effects in 500 examinations with Dimer-X is unimportant."}
{"id": "PMID:207129", "title": "Xeroradiography. Its value in gas myelography.", "content": "Electrostatic imaging with its capacity for enhancing borders improves radiographic demonstration of gas-soft tissue interfaces in gas myelography. Its wide recording latitude also provides satisfactory delineation through areas of widely varying photon absorption. Xeroradiogrphy surmounts the paradox wherein contrast and latitude are inversely related so that the combination of both high contrast and broad latitude are simultaneously used to advantage. The xerogram, especially in the thoracic region, may be sufficiently diagnostic so that tomography is not necessary. Where additional information is required, tomographic xeroradiography can provide diagnostic information not perceptible on film tomograms.", "contents": "Xeroradiography. Its value in gas myelography. Electrostatic imaging with its capacity for enhancing borders improves radiographic demonstration of gas-soft tissue interfaces in gas myelography. Its wide recording latitude also provides satisfactory delineation through areas of widely varying photon absorption. Xeroradiogrphy surmounts the paradox wherein contrast and latitude are inversely related so that the combination of both high contrast and broad latitude are simultaneously used to advantage. The xerogram, especially in the thoracic region, may be sufficiently diagnostic so that tomography is not necessary. Where additional information is required, tomographic xeroradiography can provide diagnostic information not perceptible on film tomograms."}
{"id": "PMID:207130", "title": "Orbital phlebography in evaluation of the cavernous sinus and adjacent basal veins of the skull.", "content": "Frontal vein phlebography has proven to be of great diagnostic value in the evaluation of pituitary tumours and of lesions in the vicinity of the sella turcica. It permits the diagnosis of venous thrombosis; similar phlebographic changes may be the only positive radiologic finding in cases with malignant tumour of the skull base. Phlebography is thus to be recommended as an early method to be used in possibly malignant lesions at the skull base.", "contents": "Orbital phlebography in evaluation of the cavernous sinus and adjacent basal veins of the skull. Frontal vein phlebography has proven to be of great diagnostic value in the evaluation of pituitary tumours and of lesions in the vicinity of the sella turcica. It permits the diagnosis of venous thrombosis; similar phlebographic changes may be the only positive radiologic finding in cases with malignant tumour of the skull base. Phlebography is thus to be recommended as an early method to be used in possibly malignant lesions at the skull base."}
{"id": "PMID:207131", "title": "Postural scintimyelography and dynamic CSF-pressure measurements in cervical myelopathy.", "content": "Postural scintimyelography is a refinement of scintimyelography and in combination with Queckenstedt's test proved to be an exellent screening method for possible space occupying lesions in the cervical subarachnoid space. The results in a material of 96 patients are reported. Agreement between both methods is of high clinical significance.", "contents": "Postural scintimyelography and dynamic CSF-pressure measurements in cervical myelopathy. Postural scintimyelography is a refinement of scintimyelography and in combination with Queckenstedt's test proved to be an exellent screening method for possible space occupying lesions in the cervical subarachnoid space. The results in a material of 96 patients are reported. Agreement between both methods is of high clinical significance."}
{"id": "PMID:207132", "title": "Videodensitometry of cerebrospinal fluid pulsations.", "content": "Roentgen videodensitometry (RVD) during myelography is described in 13 patients with a variety of intraspinal lesions. Abnormalities in the RVD tracing are discussed and correlated with the type of spinal canal obstruction. Intramedullary, intradural and extradural processes may be differentiated by RVD.", "contents": "Videodensitometry of cerebrospinal fluid pulsations. Roentgen videodensitometry (RVD) during myelography is described in 13 patients with a variety of intraspinal lesions. Abnormalities in the RVD tracing are discussed and correlated with the type of spinal canal obstruction. Intramedullary, intradural and extradural processes may be differentiated by RVD."}
{"id": "PMID:207134", "title": "Metrizamide, the new water-soluble non-ionic contrast medium for myelography. Clinical experience.", "content": "A survey is made of the development of water-soluble contrast media and of the experimental and preliminary clinical investigations of the new water-soluble contrast medium metrizamide. The experiences with the medium indicate that its use in the subarachnoid space is safe and reliable.", "contents": "Metrizamide, the new water-soluble non-ionic contrast medium for myelography. Clinical experience. A survey is made of the development of water-soluble contrast media and of the experimental and preliminary clinical investigations of the new water-soluble contrast medium metrizamide. The experiences with the medium indicate that its use in the subarachnoid space is safe and reliable."}
{"id": "PMID:207135", "title": "Perfluoro carbon bromides as contrast media in radiography of the central nervous system. A preliminary experimental report.", "content": "A preliminary investigation of the properties of perfluorooctyl bromide in the subarachnoid space revealed this compound to have suitable attenuation capacity and advantageous physical and biologic properties for demonstration of the brain and spinal cord. No acute or chronic neurotoxicity was encountered. Microscopy demonstrated evidence of chronic inflammatory changes subsequent to long term exposure to the compound. It was concluded that the medium was superior to iodophendylate in several respects and that it may provide an alternative to water-soluble contrast media. Perfluorohexyl bromide proved unsuitable for neuroradiologic use because of formation of excessive amounts of non-absorbable gas, leading to high subarachnoid pressure and severe neurologic deficits.", "contents": "Perfluoro carbon bromides as contrast media in radiography of the central nervous system. A preliminary experimental report. A preliminary investigation of the properties of perfluorooctyl bromide in the subarachnoid space revealed this compound to have suitable attenuation capacity and advantageous physical and biologic properties for demonstration of the brain and spinal cord. No acute or chronic neurotoxicity was encountered. Microscopy demonstrated evidence of chronic inflammatory changes subsequent to long term exposure to the compound. It was concluded that the medium was superior to iodophendylate in several respects and that it may provide an alternative to water-soluble contrast media. Perfluorohexyl bromide proved unsuitable for neuroradiologic use because of formation of excessive amounts of non-absorbable gas, leading to high subarachnoid pressure and severe neurologic deficits."}
{"id": "PMID:207136", "title": "Advances in ventriculography and myelography with the non-ionic constrast medium metrizamide.", "content": "Laboratory experiments in animals have shown that the non-ionic constrast medium metrizamide is well tolerated by the central nervous system. The preliminary clinical experiences have confirmed this exceptional tolerance. The extremely weak epileptogenic action of this compound represents the most important progress.", "contents": "Advances in ventriculography and myelography with the non-ionic constrast medium metrizamide. Laboratory experiments in animals have shown that the non-ionic constrast medium metrizamide is well tolerated by the central nervous system. The preliminary clinical experiences have confirmed this exceptional tolerance. The extremely weak epileptogenic action of this compound represents the most important progress."}
{"id": "PMID:207137", "title": "Metrizamide in radiography of the central nervous system. A preliminary report.", "content": "Metrizamide seems to be a suitable contrast medium for ventriculography and myelography. This contrast medium is less toxic and far less epileptogenic and spasmogenic than the other water-soluble contrast media in current use. No serious complications were noted in the present series. Transient changes in EEG were recorded, mainly with cervical myelographies. However, it is too early to evaluate the long-term side effects.", "contents": "Metrizamide in radiography of the central nervous system. A preliminary report. Metrizamide seems to be a suitable contrast medium for ventriculography and myelography. This contrast medium is less toxic and far less epileptogenic and spasmogenic than the other water-soluble contrast media in current use. No serious complications were noted in the present series. Transient changes in EEG were recorded, mainly with cervical myelographies. However, it is too early to evaluate the long-term side effects."}
{"id": "PMID:207138", "title": "Preliminary experiences with the EMI scanner.", "content": "Preliminary experiences of computed tomography of the head are reported in a material of 213 patients. The majority of examined lesions includes intracranial tumours and cerebrovascular lesions.", "contents": "Preliminary experiences with the EMI scanner. Preliminary experiences of computed tomography of the head are reported in a material of 213 patients. The majority of examined lesions includes intracranial tumours and cerebrovascular lesions."}
{"id": "PMID:207139", "title": "First results with an EMI scanner.", "content": "The results of computer assisted tomography (80 x 80 matrix) of 600 patients are presented.", "contents": "First results with an EMI scanner. The results of computer assisted tomography (80 x 80 matrix) of 600 patients are presented."}
{"id": "PMID:207140", "title": "Correlation between the appearances of the ventricular system at carotid angiography and computer assisted axial tomography.", "content": "Computer assisted axial tomography and the venous phase of carotid angiography provide complementary assessments of the ventricular and paraventricular structures. The computer assisted tomography more readily defines the ventricular system, but can prove weak in differentiating paraventricular gliomas, solitary metastasis and infarcts. Angiography plays a major role in differentiating between these three conditions, but is poor in accurately localizing and identifying intra- and paraventricular hemorrhage which is characteristically and expeditiously uncovered by C.T. scanning.", "contents": "Correlation between the appearances of the ventricular system at carotid angiography and computer assisted axial tomography. Computer assisted axial tomography and the venous phase of carotid angiography provide complementary assessments of the ventricular and paraventricular structures. The computer assisted tomography more readily defines the ventricular system, but can prove weak in differentiating paraventricular gliomas, solitary metastasis and infarcts. Angiography plays a major role in differentiating between these three conditions, but is poor in accurately localizing and identifying intra- and paraventricular hemorrhage which is characteristically and expeditiously uncovered by C.T. scanning."}
{"id": "PMID:207142", "title": "Radiology of suprasellar ectopic pinealoma.", "content": "The radiographic and clinical findings in twenty-three recently reported cases of suprasellar ectopic pinealoma are reviewed and three previously unreported cases are described. It is concluded that suprasellar calcification is extremely rare; enlargement of the sella turcica was present in approximately 20 to 30 per cent, none demonstrated elevation of the anterior cerebral artery. Pneumography may show a smooth or irregular filling defect in the anterior part of the third ventricle. In one of the new cases there was an isotope uptake in the suprasellar region. The differential diagnosis and other clinical data are also discussed.", "contents": "Radiology of suprasellar ectopic pinealoma. The radiographic and clinical findings in twenty-three recently reported cases of suprasellar ectopic pinealoma are reviewed and three previously unreported cases are described. It is concluded that suprasellar calcification is extremely rare; enlargement of the sella turcica was present in approximately 20 to 30 per cent, none demonstrated elevation of the anterior cerebral artery. Pneumography may show a smooth or irregular filling defect in the anterior part of the third ventricle. In one of the new cases there was an isotope uptake in the suprasellar region. The differential diagnosis and other clinical data are also discussed."}
{"id": "PMID:207143", "title": "Accuracy of scanning, angiography and encephalography in posterior fossa tumors.", "content": "A material of 120 cases with posterior fossa tumors examined with scanning, vertebral angiography and encephalography was reviewed to determine the value of the information and accuracy these methods provide. Encephalography was the most accurate procedure (98% positive) compared to angiography (81%) and scanning (44%).", "contents": "Accuracy of scanning, angiography and encephalography in posterior fossa tumors. A material of 120 cases with posterior fossa tumors examined with scanning, vertebral angiography and encephalography was reviewed to determine the value of the information and accuracy these methods provide. Encephalography was the most accurate procedure (98% positive) compared to angiography (81%) and scanning (44%)."}
{"id": "PMID:207144", "title": "Technique for internal auditory cisternography.", "content": "A technique for internal auditory cisternography is described. A small volume of Iophendylate is used and coronal hypocycloid tomographic sections of the dependent internal auditory canal and adjacent cerebellopontine angle cistern performed.", "contents": "Technique for internal auditory cisternography. A technique for internal auditory cisternography is described. A small volume of Iophendylate is used and coronal hypocycloid tomographic sections of the dependent internal auditory canal and adjacent cerebellopontine angle cistern performed."}
{"id": "PMID:207145", "title": "Quantitative analysis of the pituitary fossa and gland in Cushing's disease.", "content": "With tomography and encephalography of 78 cases with primary Cushing's disease, changes in the appearance of the pituitary gland and fossa have been demonstrated in greater numbers than previously reported. One or more direct or indirect signs of enlargement of the pituitary gland either by hyperplasia, microadenoma, or adenoma occurred in 60 per cent. Most of these cases were unproved as to cell type because they were given proton beam therapy. There were more cases of pituitary enlargement in those with adrenalectomy in comparison to non-adrenalectomy cases and in those with pigmentation in comparison to non-pigmented cases. The high incidence of pituitary gland enlargement in the different phases of this disease supports the importance of this gland in the pathogenesis of primary Cushing's disease. Limitation in correlation of the pituitary fossa to size of the pituitary gland when the latter enlarges only slightly has been discussed.", "contents": "Quantitative analysis of the pituitary fossa and gland in Cushing's disease. With tomography and encephalography of 78 cases with primary Cushing's disease, changes in the appearance of the pituitary gland and fossa have been demonstrated in greater numbers than previously reported. One or more direct or indirect signs of enlargement of the pituitary gland either by hyperplasia, microadenoma, or adenoma occurred in 60 per cent. Most of these cases were unproved as to cell type because they were given proton beam therapy. There were more cases of pituitary enlargement in those with adrenalectomy in comparison to non-adrenalectomy cases and in those with pigmentation in comparison to non-pigmented cases. The high incidence of pituitary gland enlargement in the different phases of this disease supports the importance of this gland in the pathogenesis of primary Cushing's disease. Limitation in correlation of the pituitary fossa to size of the pituitary gland when the latter enlarges only slightly has been discussed."}
{"id": "PMID:207146", "title": "Developmental defects of the cerebellum. A radiologic and anatomic investigation.", "content": "A classification of cerebellar malformations is proposed, based on more than fifty cases with varying degrees of abnormality, where comparative anatomic and radiologic analysis was carried out. The anatomic information was collected at surgery or autopsy and the radiologic evidence was derived from encephalography or ventriculography and vertebral angiography. The malformations were classified in four groups in order of gravity, with regard to the morphologic and etiologic features: (1) total or sub-total agenesia of the cerebellar structures (vermis and hemispheres); (2) almost complete agenesia of the vermis associated with the Dandy-Walker malformation; (3) almost complete agenesia of the vermis without the Dandy-Walker malformation; (4) partial defects of the vermis, which could be separated into four subdivisions.", "contents": "Developmental defects of the cerebellum. A radiologic and anatomic investigation. A classification of cerebellar malformations is proposed, based on more than fifty cases with varying degrees of abnormality, where comparative anatomic and radiologic analysis was carried out. The anatomic information was collected at surgery or autopsy and the radiologic evidence was derived from encephalography or ventriculography and vertebral angiography. The malformations were classified in four groups in order of gravity, with regard to the morphologic and etiologic features: (1) total or sub-total agenesia of the cerebellar structures (vermis and hemispheres); (2) almost complete agenesia of the vermis associated with the Dandy-Walker malformation; (3) almost complete agenesia of the vermis without the Dandy-Walker malformation; (4) partial defects of the vermis, which could be separated into four subdivisions."}
{"id": "PMID:207147", "title": "Prolactin-secreting pituitary microadenomas.", "content": "Prolactin-secreting pituitary microadenomas have been surgically selectively removed in 20 patients presenting an amenorrhea-galactorrhea syndrome, hyperprolactinemia and radiological modifications of the sella turcica. In these patients, the sella was of normal size but hypocyloidal tomography evidenced subtle changes characterizing pituitary microadenomas. The surgical intervention has been based on the twin criteria of hyperprolactinemia and sellar findings.", "contents": "Prolactin-secreting pituitary microadenomas. Prolactin-secreting pituitary microadenomas have been surgically selectively removed in 20 patients presenting an amenorrhea-galactorrhea syndrome, hyperprolactinemia and radiological modifications of the sella turcica. In these patients, the sella was of normal size but hypocyloidal tomography evidenced subtle changes characterizing pituitary microadenomas. The surgical intervention has been based on the twin criteria of hyperprolactinemia and sellar findings."}
{"id": "PMID:207148", "title": "Iatrogenic intracranial aneurysms.", "content": "Intracranial aneurysms following head trauma are not uncommon. Few cases of iatrogenic intracranial aneurysm have been reported however. This type of lesion is illustrated by three cases. If these lesions have the same poor prognosis as that proposed for the usual traumatic aneurysm, their early diagnosis and treatment is important.", "contents": "Iatrogenic intracranial aneurysms. Intracranial aneurysms following head trauma are not uncommon. Few cases of iatrogenic intracranial aneurysm have been reported however. This type of lesion is illustrated by three cases. If these lesions have the same poor prognosis as that proposed for the usual traumatic aneurysm, their early diagnosis and treatment is important."}
{"id": "PMID:207149", "title": "Accessory meningeal artery.", "content": "The accessory meningeal artery, originating from either the internal maxillary or middle meningeal artery, is predominantly an extracranial vessel. A minor branch of the artery enters the skull through the foramen ovale to supply the dura of the temporal fossa as well as the Gasserian ganglion. This intracranial branch may be demonstrated on angiography and may serve as a collateral between the external and the internal carotid arteries, with or without a complex intervening vascular network. The accessory meningeal artery may be identified as the arterial pedicle responsible for blood supply to meningiomas of the temporal fossa and possibly even to tumors of the Gasserian ganglion.", "contents": "Accessory meningeal artery. The accessory meningeal artery, originating from either the internal maxillary or middle meningeal artery, is predominantly an extracranial vessel. A minor branch of the artery enters the skull through the foramen ovale to supply the dura of the temporal fossa as well as the Gasserian ganglion. This intracranial branch may be demonstrated on angiography and may serve as a collateral between the external and the internal carotid arteries, with or without a complex intervening vascular network. The accessory meningeal artery may be identified as the arterial pedicle responsible for blood supply to meningiomas of the temporal fossa and possibly even to tumors of the Gasserian ganglion."}
{"id": "PMID:207150", "title": "Radiologic evaluation of the function of the cervical spine.", "content": "Cervical functional examinations initiated in 1965 suggested the need of a correlated, multifactorial expression of the cervical sagittal movement function, allowing comparative evaluations of physiologic-diagnostic significance. Technical aspects of the successive steps of investigation, together with the final morphologic-functional formula are described. The significance of the normal and abnormal functional patterns, identified in a selected series of 300 cases, is finally discussed.", "contents": "Radiologic evaluation of the function of the cervical spine. Cervical functional examinations initiated in 1965 suggested the need of a correlated, multifactorial expression of the cervical sagittal movement function, allowing comparative evaluations of physiologic-diagnostic significance. Technical aspects of the successive steps of investigation, together with the final morphologic-functional formula are described. The significance of the normal and abnormal functional patterns, identified in a selected series of 300 cases, is finally discussed."}
{"id": "PMID:207151", "title": "Fusiform aneurysmal dilatation of pericallosal artery. A sign of lipoma of corpus callosum.", "content": "Two cases of lipoma of the corpus callosum with aneurysmal dilatation of the pericallosal artery are reported. This appears to be a reliable sign of lipoma of the corpus callosum. Our cases and the literature reveal that 19 of 22 cases with illustrations of carotid angiography have demonstrated such an aneurysmal dilatation.", "contents": "Fusiform aneurysmal dilatation of pericallosal artery. A sign of lipoma of corpus callosum. Two cases of lipoma of the corpus callosum with aneurysmal dilatation of the pericallosal artery are reported. This appears to be a reliable sign of lipoma of the corpus callosum. Our cases and the literature reveal that 19 of 22 cases with illustrations of carotid angiography have demonstrated such an aneurysmal dilatation."}
{"id": "PMID:207152", "title": "Early venous filling and controlled hyperventilation in cerebral angiography.", "content": "Controlled hyperventilation is a useful adjunct to angiography of tumours and inflammatory disease, giving increased demonstration of normal penetrating arteries and abnormal vessels. This shunting effect commonly causes early filling of the deep ependymal veins which should not be mistaken for early venous return due to tumour. While the effect could theoretically mask early venous flow secondary to tumour, this has not been our experience.", "contents": "Early venous filling and controlled hyperventilation in cerebral angiography. Controlled hyperventilation is a useful adjunct to angiography of tumours and inflammatory disease, giving increased demonstration of normal penetrating arteries and abnormal vessels. This shunting effect commonly causes early filling of the deep ependymal veins which should not be mistaken for early venous return due to tumour. While the effect could theoretically mask early venous flow secondary to tumour, this has not been our experience."}
{"id": "PMID:207153", "title": "Sylvian triangle. Angiographic evaluation of its appearance in normal and pathologic conditions.", "content": "Description of a method for determining the size of the Sylvian triangle on lateral films. A cranio-insular index is constructed which allows differentiation between normal cases, paracapsular and subdural hematomas.", "contents": "Sylvian triangle. Angiographic evaluation of its appearance in normal and pathologic conditions. Description of a method for determining the size of the Sylvian triangle on lateral films. A cranio-insular index is constructed which allows differentiation between normal cases, paracapsular and subdural hematomas."}
{"id": "PMID:207154", "title": "[Effects of intrathoracic pressure on cerebral circulation in the monkey as a function of body posture, sitting or standing].", "content": "Sixty-four measurements of CBF were performed in 8 monkeys in supine and in sitting position under various conditions of ventilation. The position of the body does not normally influence the response of brain circulation to CO2. The response is not different from normal with high insufflation pressure in supine position and the capacities to autoregulation seem to be maintained. In vertical position however there are no longer any significant relations between CBF and PaCO2, and the loss of autoregulation seems to occur earlier and to be more marked. Correlation of these findings to neuroradiologic data indicates that the cerebral venous drainage through the meningospinal plexus is enhanced in vertical position and that during intrathoracic hyperpressure the cerebral venous blood is retained in the jugular vein and meningospinal plexus, thus decreasing the cerebral venous pressure increase and maintaining a perfusion of brain tissue compatible with the survival of the animal.", "contents": "[Effects of intrathoracic pressure on cerebral circulation in the monkey as a function of body posture, sitting or standing]. Sixty-four measurements of CBF were performed in 8 monkeys in supine and in sitting position under various conditions of ventilation. The position of the body does not normally influence the response of brain circulation to CO2. The response is not different from normal with high insufflation pressure in supine position and the capacities to autoregulation seem to be maintained. In vertical position however there are no longer any significant relations between CBF and PaCO2, and the loss of autoregulation seems to occur earlier and to be more marked. Correlation of these findings to neuroradiologic data indicates that the cerebral venous drainage through the meningospinal plexus is enhanced in vertical position and that during intrathoracic hyperpressure the cerebral venous blood is retained in the jugular vein and meningospinal plexus, thus decreasing the cerebral venous pressure increase and maintaining a perfusion of brain tissue compatible with the survival of the animal."}
{"id": "PMID:207155", "title": "Phlebographic appearance and pathogenesis of venous malformations in the orbit.", "content": "A retrospective clinical and radiographic analysis of 20 patients with orbital venous malformations was performed. The malformations were fed by other veins rather than arteries. They may nearly always be demonstrated by orbital or jugular phlebography, though occasionally they will fill only following direct puncture. There appeared to be varied etiologies. A few were related to trauma or to other causes of increased intraorbital pressure. There is an association with periorbital hemangiomas suggesting developmental or congenital origin.", "contents": "Phlebographic appearance and pathogenesis of venous malformations in the orbit. A retrospective clinical and radiographic analysis of 20 patients with orbital venous malformations was performed. The malformations were fed by other veins rather than arteries. They may nearly always be demonstrated by orbital or jugular phlebography, though occasionally they will fill only following direct puncture. There appeared to be varied etiologies. A few were related to trauma or to other causes of increased intraorbital pressure. There is an association with periorbital hemangiomas suggesting developmental or congenital origin."}
{"id": "PMID:207156", "title": "Cerebral arterial spasm. II. Etiology and treatment of experimental cerebral vasospasm.", "content": "Delayed cerebral vasospams is caused by excessive accumulation of dopamine-beta-hydroxylase (DBH) and noradrenaline in cerebral vessel walls. This study demonstrates the mechanisms of delayed spasm, particularly the role of red blood cell components, and the successful relief of delayed cerebral vasospasm. Spasmogenic substances which contained a heme component, such as methemoglobin, methemalbumin and catalase enhanced DBH activity in human serum as measured by a one step chemical spectrophotometric assay. The concentration which gave the highest DBH activity caused the maximum constriction of the basilar artery, when the substances were applied topically. Among components of red cells, methemoglobin, methemalbumin, catalase and nicotinamid adenin dinucleotide (NADH) caused constriction of basilar artery in cats, when applied topically, whereas hematin, hemin and bilirubin caused no significant spasm. An oxyhemoglobin solution obtained by mixture with methemoglobin and ascorbic acid produced no significant vascular spasm either. Relief of delayed cerebral vasospasm was obtained with topical application of specific alpha adrenergic blocking drug such as phenoxybenzamine, specific inhibitors of DBH such as fusaric acid, o-phenanthroline and alphaalpha' dipyridyl beta2 adrenergic stimulants such as salbutamol, and a phosphodiesterase inhibitor, ascorbic acid.", "contents": "Cerebral arterial spasm. II. Etiology and treatment of experimental cerebral vasospasm. Delayed cerebral vasospams is caused by excessive accumulation of dopamine-beta-hydroxylase (DBH) and noradrenaline in cerebral vessel walls. This study demonstrates the mechanisms of delayed spasm, particularly the role of red blood cell components, and the successful relief of delayed cerebral vasospasm. Spasmogenic substances which contained a heme component, such as methemoglobin, methemalbumin and catalase enhanced DBH activity in human serum as measured by a one step chemical spectrophotometric assay. The concentration which gave the highest DBH activity caused the maximum constriction of the basilar artery, when the substances were applied topically. Among components of red cells, methemoglobin, methemalbumin, catalase and nicotinamid adenin dinucleotide (NADH) caused constriction of basilar artery in cats, when applied topically, whereas hematin, hemin and bilirubin caused no significant spasm. An oxyhemoglobin solution obtained by mixture with methemoglobin and ascorbic acid produced no significant vascular spasm either. Relief of delayed cerebral vasospasm was obtained with topical application of specific alpha adrenergic blocking drug such as phenoxybenzamine, specific inhibitors of DBH such as fusaric acid, o-phenanthroline and alphaalpha' dipyridyl beta2 adrenergic stimulants such as salbutamol, and a phosphodiesterase inhibitor, ascorbic acid."}
{"id": "PMID:207157", "title": "Dedifferentiation and invasive growth of an eosinophil pituitary adenoma.", "content": "This report concerns the course of an eosinophil pituitary adenoma in an acromegalic female (16 years of age when first symptoms appeared) over a period of ten years. The case was complicated by craniocerebral trauma and CSF rhinorrhoea. After several operations, dedifferentiation, and invasive growth into the orbit and the petrous bone were observed with walling in of the VIIIth cranial nerve. The possible causes of the dedifferentiation of the adenoma are discussed.", "contents": "Dedifferentiation and invasive growth of an eosinophil pituitary adenoma. This report concerns the course of an eosinophil pituitary adenoma in an acromegalic female (16 years of age when first symptoms appeared) over a period of ten years. The case was complicated by craniocerebral trauma and CSF rhinorrhoea. After several operations, dedifferentiation, and invasive growth into the orbit and the petrous bone were observed with walling in of the VIIIth cranial nerve. The possible causes of the dedifferentiation of the adenoma are discussed."}
{"id": "PMID:207161", "title": "The mode of action of the nicotinic cholinergic receptor protein in the postsynaptic membrane.", "content": "The functional properties of the cholinergic (nicotinic) receptor protein were discussed. on the basis of in vitro studies of membrane fragments of Electrophorus and Torpedo electric tissues. The membrane fragments of both are excitable in vitro. In contrast with the membrane fragments of Electrophorus, however, those of Torpedo give dose-response curves of in vitro excitation that shift towards higher concentration of the agonists by one to two orders of magnitude compared with the actual binding curves of agonists to the receptor sites. Moreover, they exhibit the phenomenon of pharmacological desensitization in a completely cell-free system. It was suggested that the discrepancy between the dose-response and the binding curves is related to the desensitization. The mechanism and the molecular events of desensitization are discussed. Desensitization is a reflection of a conformational change of the receptor protein during the excitation caused by agonists. This conformational change causes desensitization in subsynaptic membranes, through amplification. The regulatory properties of the cholinergic receptor protein similar to those of allosteric enzymes were discussed", "contents": "The mode of action of the nicotinic cholinergic receptor protein in the postsynaptic membrane. The functional properties of the cholinergic (nicotinic) receptor protein were discussed. on the basis of in vitro studies of membrane fragments of Electrophorus and Torpedo electric tissues. The membrane fragments of both are excitable in vitro. In contrast with the membrane fragments of Electrophorus, however, those of Torpedo give dose-response curves of in vitro excitation that shift towards higher concentration of the agonists by one to two orders of magnitude compared with the actual binding curves of agonists to the receptor sites. Moreover, they exhibit the phenomenon of pharmacological desensitization in a completely cell-free system. It was suggested that the discrepancy between the dose-response and the binding curves is related to the desensitization. The mechanism and the molecular events of desensitization are discussed. Desensitization is a reflection of a conformational change of the receptor protein during the excitation caused by agonists. This conformational change causes desensitization in subsynaptic membranes, through amplification. The regulatory properties of the cholinergic receptor protein similar to those of allosteric enzymes were discussed"}
{"id": "PMID:207168", "title": "Cytochrome oxidase and urate oxidase as intracellular O2 indicators in studies of O2 gradients during hypoxia in liver.", "content": "Results obtained from a new approach of investigating O2 distribution in intact perfused liver under hypoxic conditions are presented. Based on the signals observed by organ absorbance spectrophotometry from two compartments with oxidases of markedly different O2 sensitivity, the mitochondria and the peroxisomes, a distribution between high O2 and zero O2 zones is postulated, an intermediate border zone of O2 concentrations between the K0,5 (O2) values being virtually absent (steep intercellular O2 gradients).", "contents": "Cytochrome oxidase and urate oxidase as intracellular O2 indicators in studies of O2 gradients during hypoxia in liver. Results obtained from a new approach of investigating O2 distribution in intact perfused liver under hypoxic conditions are presented. Based on the signals observed by organ absorbance spectrophotometry from two compartments with oxidases of markedly different O2 sensitivity, the mitochondria and the peroxisomes, a distribution between high O2 and zero O2 zones is postulated, an intermediate border zone of O2 concentrations between the K0,5 (O2) values being virtually absent (steep intercellular O2 gradients)."}
{"id": "PMID:207169", "title": "Transient metabolic and vascular volume changes following rapid blood pressure alterations which precede the autoregulatory vasodilation of cerebrocortical vessels.", "content": "It has been shown by surface fluoro-reflectometry that stepwise decrease of arterial blood pressure causes a biphasic cerebrocortical vascular volume response. After the arterial blood pressure decrease the vascular volume first decreased and later increased. In both parts of the biphasic reflectance change, the cerebrocortical NAD-NADH redox state shifted considerably towards reduction and there was no reoxidation after the onset of cortical vasodilatation. Since a very rapid NADH reduction occurred during the first 30 secs. of the arterial hypotension in parallel with the vascular volume decrease, it is suggested that in the transient phase of arterial hypotension cerebral hypoxia may occur. Furthermore it is suggested that anaerobic tissue metabolites or some unknown NAD-NADH dependent process might dilate the cerebrocortical arterial network during the autoregulatory adjustment of CBF. The participation of the sympathetico-adrenal system in transient brain hypoxia caused by bleeding is a possibility since both the early vasoconstriction and the steep NADH reduction were prevented by the administration of phenoxybenzamine (1 mg/kg) before bleeding.", "contents": "Transient metabolic and vascular volume changes following rapid blood pressure alterations which precede the autoregulatory vasodilation of cerebrocortical vessels. It has been shown by surface fluoro-reflectometry that stepwise decrease of arterial blood pressure causes a biphasic cerebrocortical vascular volume response. After the arterial blood pressure decrease the vascular volume first decreased and later increased. In both parts of the biphasic reflectance change, the cerebrocortical NAD-NADH redox state shifted considerably towards reduction and there was no reoxidation after the onset of cortical vasodilatation. Since a very rapid NADH reduction occurred during the first 30 secs. of the arterial hypotension in parallel with the vascular volume decrease, it is suggested that in the transient phase of arterial hypotension cerebral hypoxia may occur. Furthermore it is suggested that anaerobic tissue metabolites or some unknown NAD-NADH dependent process might dilate the cerebrocortical arterial network during the autoregulatory adjustment of CBF. The participation of the sympathetico-adrenal system in transient brain hypoxia caused by bleeding is a possibility since both the early vasoconstriction and the steep NADH reduction were prevented by the administration of phenoxybenzamine (1 mg/kg) before bleeding."}
{"id": "PMID:207178", "title": "Prognostic significance of morphologic and cytochemical markers in adult acute leukemia.", "content": "Survival times in 100 cases of acute leukemia (74 granulocytic, 14 lymphocytic, and 12 undifferentiated) were correlated with classic morphologic and cytochemical criteria. The 14 patients who had lymphocytic leukemia had significantly longer survival compared with the two other groups. Undifferentiated leukemias had a shorter survival time than granulocytic leukemias. Several subclasses of granulocytic leukemias were formed according to the presence or absence of Auer rods and the percentage of peroxidase-positive blasts. Neither of these two features significantly influenced the survival of these patients. In the lymphocytic leukemia group, PAS-positive and negative leukemias had similar survival expectancies. It is concluded that division into lymphocytic and nonlymphocytic leukemias is still helpful in predicting survival times of patients who have acute leukemia, but that further subclassification of these groups based on the presence or absence of Auer rods and the percentages of peroxidase-positive blasts is of no additional benefit.", "contents": "Prognostic significance of morphologic and cytochemical markers in adult acute leukemia. Survival times in 100 cases of acute leukemia (74 granulocytic, 14 lymphocytic, and 12 undifferentiated) were correlated with classic morphologic and cytochemical criteria. The 14 patients who had lymphocytic leukemia had significantly longer survival compared with the two other groups. Undifferentiated leukemias had a shorter survival time than granulocytic leukemias. Several subclasses of granulocytic leukemias were formed according to the presence or absence of Auer rods and the percentage of peroxidase-positive blasts. Neither of these two features significantly influenced the survival of these patients. In the lymphocytic leukemia group, PAS-positive and negative leukemias had similar survival expectancies. It is concluded that division into lymphocytic and nonlymphocytic leukemias is still helpful in predicting survival times of patients who have acute leukemia, but that further subclassification of these groups based on the presence or absence of Auer rods and the percentages of peroxidase-positive blasts is of no additional benefit."}
{"id": "PMID:207180", "title": "Growth hormone deficiency, brain development, and intelligence.", "content": "Twenty-nine patients with growth hormone (GH) deficiency were selected according to the following criteria: no evidence of reversible GH deficiency, onset of growth retardation in early childhood, and no evidence of pituitary tumors or other direct pituitary trauma. Fourteen patients had evidence of multiple hormone deficiencies, 14 had isolated GH deficiency, and one patient questionable isolated GH deficiency. Psychometric testing showed a normal IQ distribution. The GH deficiency was not associated with deficiencies in specific mental abilities. Likewise, GH treatment in later childhood and adolescence did not seem to influence intelligence. Patients with multiple hormone deficiencies had somewhat lower IQs than patients with isolated GH deficiency when socioeconomic status was controlled. We conclude that GH deficiency itself does not seem to affect human brain development and intelligence.", "contents": "Growth hormone deficiency, brain development, and intelligence. Twenty-nine patients with growth hormone (GH) deficiency were selected according to the following criteria: no evidence of reversible GH deficiency, onset of growth retardation in early childhood, and no evidence of pituitary tumors or other direct pituitary trauma. Fourteen patients had evidence of multiple hormone deficiencies, 14 had isolated GH deficiency, and one patient questionable isolated GH deficiency. Psychometric testing showed a normal IQ distribution. The GH deficiency was not associated with deficiencies in specific mental abilities. Likewise, GH treatment in later childhood and adolescence did not seem to influence intelligence. Patients with multiple hormone deficiencies had somewhat lower IQs than patients with isolated GH deficiency when socioeconomic status was controlled. We conclude that GH deficiency itself does not seem to affect human brain development and intelligence."}
{"id": "PMID:207181", "title": "Superoxide generation by human monocytes and macrophages.", "content": "Intracellular and extracellular superoxide (O2.-) generation by human monocytes and macrophages was quantitated by the nitroblue tetrazolium (NBT) reduction method. Human monocytes reduced 4.4 +/- 0.9 nmoles/10(6) cells/15 minutes with an increase to 12.4 +/- 1.3 during phagocytosis of zymosan. Based on inhibition by superoxide dismutase, superoxide generation of these cells was 1.8 +/- 0.9 nmoles in the resting state and 16.8 +/- 2.8 nmoles with zymosan phagocytosis. Human macrophages obtained by thoracentesis had comparable levels of NBT reduction and O2.-generation. Monocytes from a patient with chronic granulomatous disease demonstrated no increment in O2.-production during phagocytosis. Thus, human monocytes and macrophages appear capable of generating substantial amounts of O2.-during phagocytosis which may play an important role in bactericidal and other cell functions.", "contents": "Superoxide generation by human monocytes and macrophages. Intracellular and extracellular superoxide (O2.-) generation by human monocytes and macrophages was quantitated by the nitroblue tetrazolium (NBT) reduction method. Human monocytes reduced 4.4 +/- 0.9 nmoles/10(6) cells/15 minutes with an increase to 12.4 +/- 1.3 during phagocytosis of zymosan. Based on inhibition by superoxide dismutase, superoxide generation of these cells was 1.8 +/- 0.9 nmoles in the resting state and 16.8 +/- 2.8 nmoles with zymosan phagocytosis. Human macrophages obtained by thoracentesis had comparable levels of NBT reduction and O2.-generation. Monocytes from a patient with chronic granulomatous disease demonstrated no increment in O2.-production during phagocytosis. Thus, human monocytes and macrophages appear capable of generating substantial amounts of O2.-during phagocytosis which may play an important role in bactericidal and other cell functions."}
{"id": "PMID:207182", "title": "Uridine monophosphate kinase polymorphism in two Venezuelan populations.", "content": "A study of the uridine monophosphate kinase (UMPK) electrophoretic patterns in Venezuelan individuals from the mestizo population of Caracas and from the Warao Indians of the Nabasanuka village in the Delta of the Orinoco River are reported. Among the mestizo population, the frequency of the UMPK1, UMPK2, and UMPK3 alleles was .979, .020, and .001, respectively. A higher frequency of the UMPK3 gene was seen in the highly inbred Warao Indians than any other population studied to date.", "contents": "Uridine monophosphate kinase polymorphism in two Venezuelan populations. A study of the uridine monophosphate kinase (UMPK) electrophoretic patterns in Venezuelan individuals from the mestizo population of Caracas and from the Warao Indians of the Nabasanuka village in the Delta of the Orinoco River are reported. Among the mestizo population, the frequency of the UMPK1, UMPK2, and UMPK3 alleles was .979, .020, and .001, respectively. A higher frequency of the UMPK3 gene was seen in the highly inbred Warao Indians than any other population studied to date."}
{"id": "PMID:207185", "title": "Consensual reactions to anterior chamber paracentesis in the rabbit.", "content": "A consensual reaction was consistently obtained in rabbits subjected to unilateral paracentesis. On fluorescein angiography of the anterior segment, we observed that this consensual reaction consisted of a slight to moderate dye extravasation from the ciliary processes into the aqueous. Aspirin usually, but not always, inhibited this reaction. Retrobulbar injection of anesthesia to the injured eye always blocked the consensual response, as did phenoxybenzamine injected intravenously before the paracentesis. We concluded that consensual responses are more efficiently inhibited by nerve-blocking agents than by prostaglandin inhibitors. These results suggest that the interocular pathway mediating consensual responses is probably neural and not caused by prostaglandins released into the general circulation.", "contents": "Consensual reactions to anterior chamber paracentesis in the rabbit. A consensual reaction was consistently obtained in rabbits subjected to unilateral paracentesis. On fluorescein angiography of the anterior segment, we observed that this consensual reaction consisted of a slight to moderate dye extravasation from the ciliary processes into the aqueous. Aspirin usually, but not always, inhibited this reaction. Retrobulbar injection of anesthesia to the injured eye always blocked the consensual response, as did phenoxybenzamine injected intravenously before the paracentesis. We concluded that consensual responses are more efficiently inhibited by nerve-blocking agents than by prostaglandin inhibitors. These results suggest that the interocular pathway mediating consensual responses is probably neural and not caused by prostaglandins released into the general circulation."}
{"id": "PMID:207186", "title": "Orbital fibrous histiocytoma in an infant.", "content": "A case of fibrous histiocytoma of the orbit occurred in a 1-year-old infant. The tumor was excised, and no recurrence has been evident.", "contents": "Orbital fibrous histiocytoma in an infant. A case of fibrous histiocytoma of the orbit occurred in a 1-year-old infant. The tumor was excised, and no recurrence has been evident."}
{"id": "PMID:207187", "title": "The lung of the copper-deficient rat. A model for developmental pulmonary emphysema.", "content": "Based on the hypothesis that cross-linked elastin is critical for normal lung structure, lung tissue from copper-deficient rats was studied. Copper deficiency was induced in the second generation by feeding dams a milk-based diet low in copper (less than 1 ppm) during gestation and lactation. The weanlings were fed the same diet until they showed severe signs of deficiency between 6 and 10 weeks of age. Controls animals received the basal diet supplemented with 10 ppm copper. Liver cytochrome oxidase activity, which served as the chief index of deficiency, decreased from a normal level of approximately 80 to 15 mumole/min/g. The lungs of the deficient animals contained 17% less elastin and had 35% larger alveolar spaces (34.7 vs 47.7 intercepts), as determined by the mean alveolar intercept method. The ultrastructure of elastin in the bronchi, arterioles, and alveolar ducts had a \"washed out\" appearance. To determine the reversibility of the pathology, deficient animals, 5 to 10 weeks of age, were repleted by feeding a copper-supplemented diet for 1, 2, and 3 months. During this period growth resumed, anemia disappeared, and liver cytochrome oxidase returned to normal. There was no improvement in lung structure with regard to alveolar size (28.4 intercepts compared with 43.6 in controls and 35.1 in deficient littermates killed at the start of repletion). The ultrastructure and electron density of pulmonary elastin was restored to near normal. The lung of the copper-deficient rat is proposed as a model for developmental pulmonary emphysema.", "contents": "The lung of the copper-deficient rat. A model for developmental pulmonary emphysema. Based on the hypothesis that cross-linked elastin is critical for normal lung structure, lung tissue from copper-deficient rats was studied. Copper deficiency was induced in the second generation by feeding dams a milk-based diet low in copper (less than 1 ppm) during gestation and lactation. The weanlings were fed the same diet until they showed severe signs of deficiency between 6 and 10 weeks of age. Controls animals received the basal diet supplemented with 10 ppm copper. Liver cytochrome oxidase activity, which served as the chief index of deficiency, decreased from a normal level of approximately 80 to 15 mumole/min/g. The lungs of the deficient animals contained 17% less elastin and had 35% larger alveolar spaces (34.7 vs 47.7 intercepts), as determined by the mean alveolar intercept method. The ultrastructure of elastin in the bronchi, arterioles, and alveolar ducts had a \"washed out\" appearance. To determine the reversibility of the pathology, deficient animals, 5 to 10 weeks of age, were repleted by feeding a copper-supplemented diet for 1, 2, and 3 months. During this period growth resumed, anemia disappeared, and liver cytochrome oxidase returned to normal. There was no improvement in lung structure with regard to alveolar size (28.4 intercepts compared with 43.6 in controls and 35.1 in deficient littermates killed at the start of repletion). The ultrastructure and electron density of pulmonary elastin was restored to near normal. The lung of the copper-deficient rat is proposed as a model for developmental pulmonary emphysema."}
{"id": "PMID:207188", "title": "The effect of phorbol myristate acetate on the metabolism and ultrastructure of human alveolar macrophages.", "content": "In the present investigation we examined the influence of the surface-active agent phorbol myristate acetate (PMA) and opsonized heat-killed bacteria (HKB) on oxygen consumption, superoxide release, and glucose oxidation of human alveolar macrophages (AM). Both PMA and HKB produced a surge in oxygen consumption, superoxide release, and oxidation of 1-14C-glucose and 6-14C-glucose by human AM. Examination of AM by electron microscopy following stimulation by these two agents demonstrated membrane ruffling, loss of microvilli, and increased vacuolization in PMA-treated cells and phagocytic vacuoles containing bacteria in HKB-treated cells. The vacuolization produced by PMA-treated AM was much less striking  than the vacuolization produced in PMA-treated leukocytes. The similarity in the metabolic and some of the physical responses of AM stimulated by PMA and HKB suggest that PMA may be a useful agent for evaluating cell-membrane-related events of phagocytosis in AM.", "contents": "The effect of phorbol myristate acetate on the metabolism and ultrastructure of human alveolar macrophages. In the present investigation we examined the influence of the surface-active agent phorbol myristate acetate (PMA) and opsonized heat-killed bacteria (HKB) on oxygen consumption, superoxide release, and glucose oxidation of human alveolar macrophages (AM). Both PMA and HKB produced a surge in oxygen consumption, superoxide release, and oxidation of 1-14C-glucose and 6-14C-glucose by human AM. Examination of AM by electron microscopy following stimulation by these two agents demonstrated membrane ruffling, loss of microvilli, and increased vacuolization in PMA-treated cells and phagocytic vacuoles containing bacteria in HKB-treated cells. The vacuolization produced by PMA-treated AM was much less striking  than the vacuolization produced in PMA-treated leukocytes. The similarity in the metabolic and some of the physical responses of AM stimulated by PMA and HKB suggest that PMA may be a useful agent for evaluating cell-membrane-related events of phagocytosis in AM."}
{"id": "PMID:207189", "title": "Expression of herpesvirus in adherent cells derived from bone marrow of latently infected guinea pigs.", "content": "The role of bone marrow adherent cells in the latency of guinea pig herpes-like virus (GPHLV) was explored. Cultures of macrophage-enriched adherent cells derived from infected guinea pigs were examined for evidence of latent GPHLV infection. Expression of the virus was detected in these cultures 9 to 10 days after in vitro cultivation. Increasing virus infectivity titers as well as light and electron microscopic evidence of virion assembly in macrophages and fibroblasts were demonstrated. Infections virus was detected in the bone marrow adherent cells that had attached for 30 or 120 minutes but only following reverse cocultivation. The data showed not only that the bone marrow adherent cells were susceptible to GPHLV in vitro but also that GPHLV was harbored by the macrophage-enriched bone marrow population in vivo in latently infected guinea pigs.", "contents": "Expression of herpesvirus in adherent cells derived from bone marrow of latently infected guinea pigs. The role of bone marrow adherent cells in the latency of guinea pig herpes-like virus (GPHLV) was explored. Cultures of macrophage-enriched adherent cells derived from infected guinea pigs were examined for evidence of latent GPHLV infection. Expression of the virus was detected in these cultures 9 to 10 days after in vitro cultivation. Increasing virus infectivity titers as well as light and electron microscopic evidence of virion assembly in macrophages and fibroblasts were demonstrated. Infections virus was detected in the bone marrow adherent cells that had attached for 30 or 120 minutes but only following reverse cocultivation. The data showed not only that the bone marrow adherent cells were susceptible to GPHLV in vitro but also that GPHLV was harbored by the macrophage-enriched bone marrow population in vivo in latently infected guinea pigs."}
{"id": "PMID:207191", "title": "The opiate receptor and morphine-like peptides in the brain.", "content": "Opiate receptors--neuronal membrane proteins that have been identified by the direct binding to membranes of radioactive opiates--have been shown to mediate the pharmacological effects of opiate drugs. Examination of brain extracts for substances that mimic effects of opiates on the opiate receptor permitted identification of the enkephalins, two peptides, each containing five amino acids, which are the normal substrates for the opiate receptor. Enkephalins are contained in specific neurons localized to areas of the brain enriched in opiate receptors. Enkephalin-containing neurons and opiate receptors are concentrated in portions of the brain that mediate pain perception, emotional behavior, and other functions altered by opiates. beta-Endorphin, an opiate-like peptide containing 31 amino acids, is localized to the pituitary gland from which it can be released into the circulation to act presumably at peripheral target organs. In the brain beta-endorphin is concentrated in the hypothalamus.", "contents": "The opiate receptor and morphine-like peptides in the brain. Opiate receptors--neuronal membrane proteins that have been identified by the direct binding to membranes of radioactive opiates--have been shown to mediate the pharmacological effects of opiate drugs. Examination of brain extracts for substances that mimic effects of opiates on the opiate receptor permitted identification of the enkephalins, two peptides, each containing five amino acids, which are the normal substrates for the opiate receptor. Enkephalins are contained in specific neurons localized to areas of the brain enriched in opiate receptors. Enkephalin-containing neurons and opiate receptors are concentrated in portions of the brain that mediate pain perception, emotional behavior, and other functions altered by opiates. beta-Endorphin, an opiate-like peptide containing 31 amino acids, is localized to the pituitary gland from which it can be released into the circulation to act presumably at peripheral target organs. In the brain beta-endorphin is concentrated in the hypothalamus."}
{"id": "PMID:207192", "title": "Brief versus standard hospitalization: the differential costs.", "content": "The authors compared the use of inpatient and day care services, number of readmissions, use of special services, use of drugs, costs to family and community, and differential dollar costs of three treatment approaches--brief hospitalization followed by day care, brief hospitalization followed by outpatient care, and standard hospitalization. They found that, among patients who had families willing to care for them, brief hospitalization followed by either day or outpatient care was less expensive in terms of hospital costs and costs to the family than standard hospitalization.", "contents": "Brief versus standard hospitalization: the differential costs. The authors compared the use of inpatient and day care services, number of readmissions, use of special services, use of drugs, costs to family and community, and differential dollar costs of three treatment approaches--brief hospitalization followed by day care, brief hospitalization followed by outpatient care, and standard hospitalization. They found that, among patients who had families willing to care for them, brief hospitalization followed by either day or outpatient care was less expensive in terms of hospital costs and costs to the family than standard hospitalization."}
{"id": "PMID:207193", "title": "The paradoxical underutilization of partial hospitalization.", "content": "Partial hospitalization continues to be underutilized even though its clinical effectiveness for a variety of psychiatric patients has been demonstrated. The authors investigated the potential economic advantage of partial hospitalization by comparing matched groups of day hospital patients and inpatients who had comparable symptoms and prognoses on admission. They present one-year follow-up data documenting the comparability of the study groups on clinical outcome measures and the cost advantages favorable the partial hospitalization group. They discuss possible causes of the paradoxical underutilization of the clinically effective and lower-cost partial hospitalization, which include institutional factors, patients' clinical characteristics, family resistance, and clinician bias.", "contents": "The paradoxical underutilization of partial hospitalization. Partial hospitalization continues to be underutilized even though its clinical effectiveness for a variety of psychiatric patients has been demonstrated. The authors investigated the potential economic advantage of partial hospitalization by comparing matched groups of day hospital patients and inpatients who had comparable symptoms and prognoses on admission. They present one-year follow-up data documenting the comparability of the study groups on clinical outcome measures and the cost advantages favorable the partial hospitalization group. They discuss possible causes of the paradoxical underutilization of the clinically effective and lower-cost partial hospitalization, which include institutional factors, patients' clinical characteristics, family resistance, and clinician bias."}
{"id": "PMID:207195", "title": "Electron-microscopic study of pseudo-exfoliation of the lens capsule.", "content": "The lens, iris, and ciliary body from the eyes of patients with glaucoma with cataract were examined via electron microscopy, and the following results obtained. 1. Zonular bundles were encrusted with accumulations of pseudoexfoliative (PE) materials and fragmented zonular fibrils, especially on their lateral aspects. 2. PE materials ranged from 300 to 400 A in width, consisting of several subunits about 100 A wide. 3. Pigment epithelial cells of the iris and nonpigmented epithelial cells of the ciliary process occasionally contained many phagosomes engulfing pigment granules. 4. Near the ciliary process, degenerating zonular bundles were mostly replaced with PE materials and fragmented zonular fibrils, and a gradual transition was observed between them. From the above findings, it is probable that PE material might be mainly composed of degenerated zonular fibrils, which are presumed to be digested with lysosomal enzymes.", "contents": "Electron-microscopic study of pseudo-exfoliation of the lens capsule. The lens, iris, and ciliary body from the eyes of patients with glaucoma with cataract were examined via electron microscopy, and the following results obtained. 1. Zonular bundles were encrusted with accumulations of pseudoexfoliative (PE) materials and fragmented zonular fibrils, especially on their lateral aspects. 2. PE materials ranged from 300 to 400 A in width, consisting of several subunits about 100 A wide. 3. Pigment epithelial cells of the iris and nonpigmented epithelial cells of the ciliary process occasionally contained many phagosomes engulfing pigment granules. 4. Near the ciliary process, degenerating zonular bundles were mostly replaced with PE materials and fragmented zonular fibrils, and a gradual transition was observed between them. From the above findings, it is probable that PE material might be mainly composed of degenerated zonular fibrils, which are presumed to be digested with lysosomal enzymes."}
{"id": "PMID:207207", "title": "The public health significance of mycotoxins.", "content": "Diseases of man and animals associated with foodstuffs contaminated by molds have been known for centuries, but only recently have mycotoxicoses been recognized as a significant hazard to man. A detailed review of the literature involving the major mycotoxin-producing fungi is presented. Because of their hazards to both human and animal health, increasing concern has developed regarding the carcinogenic activity of aflatoxins and other mycotoxins. The symptoms of mycotoxicoses in man and experimental animals is reviewed and certain specific case histories reported. The industry is urged to implement all available techniques in order to minimize the contamination of foods by mycotoxins.", "contents": "The public health significance of mycotoxins. Diseases of man and animals associated with foodstuffs contaminated by molds have been known for centuries, but only recently have mycotoxicoses been recognized as a significant hazard to man. A detailed review of the literature involving the major mycotoxin-producing fungi is presented. Because of their hazards to both human and animal health, increasing concern has developed regarding the carcinogenic activity of aflatoxins and other mycotoxins. The symptoms of mycotoxicoses in man and experimental animals is reviewed and certain specific case histories reported. The industry is urged to implement all available techniques in order to minimize the contamination of foods by mycotoxins."}
{"id": "PMID:207209", "title": "Cytomegalovirus retinitis: two cases occurring after renal transplantation.", "content": "Cytomegalovirus (CMV) retinitis is reported in 2 patients who received immunosuppressive medication after cadaveric renal transplantation. The clinical features of this disease as well as the differential diagnosis are presented. Reduction in the amount of immunosuppressive drugs given postoperatively is suggested as the definitive treatment of this disease. Available specific antiviral chemotherapeutic agents were ineffective against CMV retinitis. This finding may be modified at a later date, with the introduction and use of new effective and safe antiviral drugs.", "contents": "Cytomegalovirus retinitis: two cases occurring after renal transplantation. Cytomegalovirus (CMV) retinitis is reported in 2 patients who received immunosuppressive medication after cadaveric renal transplantation. The clinical features of this disease as well as the differential diagnosis are presented. Reduction in the amount of immunosuppressive drugs given postoperatively is suggested as the definitive treatment of this disease. Available specific antiviral chemotherapeutic agents were ineffective against CMV retinitis. This finding may be modified at a later date, with the introduction and use of new effective and safe antiviral drugs."}
{"id": "PMID:207214", "title": "[Frequency of viral infections (especially with herpes virus) during Darier's and Hailey-Hailey's diseases (author's transl)].", "content": "The fragility of epidermal cells in Hailey-Hailey's disease end even more in Darier's disease seems to favour the development of viral infections. The authors present six cases of herpes virus infections in three siblings with an intermediate form between Darier's disease and Hailey-Hailey's disease, both having a tendency to recur. One of the flares demonstrated signs of Kaposi and Juliusberg's pustulosis vacciniformis which is often found in the literature as a complication of Darier's disease. The authors discuss the frequency of the recurrences, which could be due to different viruses. Herpetic virus is often found, less frequently vaccinial virus, but sometimes also Coxsackie A 16 virus.", "contents": "[Frequency of viral infections (especially with herpes virus) during Darier's and Hailey-Hailey's diseases (author's transl)]. The fragility of epidermal cells in Hailey-Hailey's disease end even more in Darier's disease seems to favour the development of viral infections. The authors present six cases of herpes virus infections in three siblings with an intermediate form between Darier's disease and Hailey-Hailey's disease, both having a tendency to recur. One of the flares demonstrated signs of Kaposi and Juliusberg's pustulosis vacciniformis which is often found in the literature as a complication of Darier's disease. The authors discuss the frequency of the recurrences, which could be due to different viruses. Herpetic virus is often found, less frequently vaccinial virus, but sometimes also Coxsackie A 16 virus."}
{"id": "PMID:207210", "title": "[Double-blind comparative study of trimethroprim-sulphacetamide-polymyxin b and gentamicin in the treatment of otorrhoea (author's transl)].", "content": "A double-blind comparative study of the use of Garamycine (gentamicin) ear drops and TSP (trimethroprim-sulphacetamide-polomyxin B)  ear drops in the treatment of 100 cases of otorrhoea due to external otitis, a recurrent otitis media accompanied by perforation of the drum, an infection of the mastoid cavity or a postoperative infection, provided evidence of the effectiveness of both medications. TSP ear drops gave positive results in 42 out of 50 cases treated, whilst for gentamicin aural solution results were positive for 46 out of 50 cases. Gentamicin gave a successful result in 5 of the 8 failures with TSP, whilst TSP cured the four original failures with gentamicin. There were no signs of ototoxicity, of excessive fungal proliferation nor of any local sensitivity to the ear drops. It would seem that these aural preparations are complementary, capable of resulting in the disappearance of the majority of bacterial agents responsible for pathogenic otorrhoea.", "contents": "[Double-blind comparative study of trimethroprim-sulphacetamide-polymyxin b and gentamicin in the treatment of otorrhoea (author's transl)]. A double-blind comparative study of the use of Garamycine (gentamicin) ear drops and TSP (trimethroprim-sulphacetamide-polomyxin B)  ear drops in the treatment of 100 cases of otorrhoea due to external otitis, a recurrent otitis media accompanied by perforation of the drum, an infection of the mastoid cavity or a postoperative infection, provided evidence of the effectiveness of both medications. TSP ear drops gave positive results in 42 out of 50 cases treated, whilst for gentamicin aural solution results were positive for 46 out of 50 cases. Gentamicin gave a successful result in 5 of the 8 failures with TSP, whilst TSP cured the four original failures with gentamicin. There were no signs of ototoxicity, of excessive fungal proliferation nor of any local sensitivity to the ear drops. It would seem that these aural preparations are complementary, capable of resulting in the disappearance of the majority of bacterial agents responsible for pathogenic otorrhoea."}
{"id": "PMID:207215", "title": "[Partially hormone dependent bilateral malignant polyadenomatous hyperplasia].", "content": "Bilateral malignant polyadenomas of adrenals seem to be rare. They involve either a double primary adrenal tumour, or a metastasis of a controlateral tumour. In the observation reported here, the evolution is characterized by periods of central stimulation with partial autonomy, and periods of tumoral autonomy with central inertness. Pathological findings consist of coexistence of various histological aspects (atrophy, hyperplasia, benign adenoma, carcinoma) suggesting the successive steps of a very particuliar adrenal carcinogenesis. Such findings allow to discuss the following physiopathological mechanism: a stimulation by ACTH might have resulted initially in a preneoplasic hyperplasia, then in an incompletely autonomous tumour, and finally in an autonomous tumour. Accordingly, from a practical and therapeutic point of view, it would be suitable, after removal of an adrenal tumour, especially of one with demonstrated ACTH-dependance, to suppress totally endogenous ACTH by cortisol or cortisone therapy, in order to reduce the occurence of corticotropin stimulation of possibly remaining malignant adrenal cells.", "contents": "[Partially hormone dependent bilateral malignant polyadenomatous hyperplasia]. Bilateral malignant polyadenomas of adrenals seem to be rare. They involve either a double primary adrenal tumour, or a metastasis of a controlateral tumour. In the observation reported here, the evolution is characterized by periods of central stimulation with partial autonomy, and periods of tumoral autonomy with central inertness. Pathological findings consist of coexistence of various histological aspects (atrophy, hyperplasia, benign adenoma, carcinoma) suggesting the successive steps of a very particuliar adrenal carcinogenesis. Such findings allow to discuss the following physiopathological mechanism: a stimulation by ACTH might have resulted initially in a preneoplasic hyperplasia, then in an incompletely autonomous tumour, and finally in an autonomous tumour. Accordingly, from a practical and therapeutic point of view, it would be suitable, after removal of an adrenal tumour, especially of one with demonstrated ACTH-dependance, to suppress totally endogenous ACTH by cortisol or cortisone therapy, in order to reduce the occurence of corticotropin stimulation of possibly remaining malignant adrenal cells."}
{"id": "PMID:207211", "title": "Neurilemoma of the jugular foramen. Transmastoid removal.", "content": "The authors present two cases in which the palsies of the IX, X, XI and XII nerves heralded the presence of a neurilemoma within the jugular foramen. Temporary bone polytomography, retrograde jugular venography, and pantopaque posterior fossa myelography allowed the nature and extent of the tumor to be predicted accurately prior to the operation. The tumors were completely removed using a transmastoid-extended facial recess approach without labyrinthectomy, supplemented in one case by exploration of the upper cervical portion of the internal jugular vein. This technique has avoided the complications which attend removal by way of the posterior fossa. We feel that transmastoid removal merits more extensive clinical trial.", "contents": "Neurilemoma of the jugular foramen. Transmastoid removal. The authors present two cases in which the palsies of the IX, X, XI and XII nerves heralded the presence of a neurilemoma within the jugular foramen. Temporary bone polytomography, retrograde jugular venography, and pantopaque posterior fossa myelography allowed the nature and extent of the tumor to be predicted accurately prior to the operation. The tumors were completely removed using a transmastoid-extended facial recess approach without labyrinthectomy, supplemented in one case by exploration of the upper cervical portion of the internal jugular vein. This technique has avoided the complications which attend removal by way of the posterior fossa. We feel that transmastoid removal merits more extensive clinical trial."}
{"id": "PMID:207217", "title": "[Pituitary adenoma with alpha, 17-39 ACTH and beta, MSH cells, without hypercorticism (author's transl)].", "content": "In one case of pituitary basophil adenoma, the majority of the cells contains numerous small granulations which, by using immunohistoenzymatic technique, react with alpha, 17-39 ACTH and beta, MSH antisera. The reaction with anti beta, 1-24 ACTH is negative. The radioimmunoassay of ACTH reveals an increase of plasmatic ACTH, but the cortisol cycle stays low. This data suggests that this functional adenoma releases a product of which has an immunological relationship with ACTH, without biological activity.", "contents": "[Pituitary adenoma with alpha, 17-39 ACTH and beta, MSH cells, without hypercorticism (author's transl)]. In one case of pituitary basophil adenoma, the majority of the cells contains numerous small granulations which, by using immunohistoenzymatic technique, react with alpha, 17-39 ACTH and beta, MSH antisera. The reaction with anti beta, 1-24 ACTH is negative. The radioimmunoassay of ACTH reveals an increase of plasmatic ACTH, but the cortisol cycle stays low. This data suggests that this functional adenoma releases a product of which has an immunological relationship with ACTH, without biological activity."}
{"id": "PMID:207218", "title": "[Hyponatremia, a frequent, and at times a major and indicative sign in anterior pituitary insufficiency].", "content": "Thirty five patients with hypopituitarism have been studied. Nine had a mild hyponatremia (126-137 mEq/l) and five a profound hyponatremia (105-124 mEq/l). None of them had hemodilution (plasma protein, potassium were normal). Hyponatremia was present even in the absence of deficit in GH and/or TSH, and/or FSH-LH. All the pateints had a complete ACTH deficiency. There was a negative correlation between age and natremia (r = -0,39; p0.02). 2/5 patients with severe hyponatremia had mental confusion. These two patients had a complete TSH deficiency. Natremia increased with cortisone therapy in all cases but reached the normal range only in one case. Mental confusion disappeared and natremia became normal in all patients with therapy with cortisone and thyroid hormones.", "contents": "[Hyponatremia, a frequent, and at times a major and indicative sign in anterior pituitary insufficiency]. Thirty five patients with hypopituitarism have been studied. Nine had a mild hyponatremia (126-137 mEq/l) and five a profound hyponatremia (105-124 mEq/l). None of them had hemodilution (plasma protein, potassium were normal). Hyponatremia was present even in the absence of deficit in GH and/or TSH, and/or FSH-LH. All the pateints had a complete ACTH deficiency. There was a negative correlation between age and natremia (r = -0,39; p0.02). 2/5 patients with severe hyponatremia had mental confusion. These two patients had a complete TSH deficiency. Natremia increased with cortisone therapy in all cases but reached the normal range only in one case. Mental confusion disappeared and natremia became normal in all patients with therapy with cortisone and thyroid hormones."}
{"id": "PMID:207213", "title": "Study of 100 patients with bilateral sensorineural hearing loss for lipid abnormalities.", "content": "One hundred persons were selected from our audiology records who showed at least 20 dB bilateral sensorineural hearing loss. The number 100 was picked for an adequate statistical analysis. The patients were taken from the chart files which are filed in chronological order. Letters were mailed with instructions for fasting 14 hours prior to testing except for the consumption of water. On presentation, a history was taken for diabetes, height and weight, and the blood pressure was recorded. The blood samples were drawn in clot tubes and taken to a commercial laboratory for overnight refrigeration and testing of the serum. Testing included observation of serum for massive chylomicronemia, triglycerides, cholesterol and lipoprotein electrophoresis (by the cellulose acetate method). Lipoprotein testing results showed 12 patients with Type II A or II B and 8 patients with Type IV abnormalities. No Types I, III or V were found. These 20 patients represent a lower number of hyperlipoproteinemic patients than would be expected in the general population.", "contents": "Study of 100 patients with bilateral sensorineural hearing loss for lipid abnormalities. One hundred persons were selected from our audiology records who showed at least 20 dB bilateral sensorineural hearing loss. The number 100 was picked for an adequate statistical analysis. The patients were taken from the chart files which are filed in chronological order. Letters were mailed with instructions for fasting 14 hours prior to testing except for the consumption of water. On presentation, a history was taken for diabetes, height and weight, and the blood pressure was recorded. The blood samples were drawn in clot tubes and taken to a commercial laboratory for overnight refrigeration and testing of the serum. Testing included observation of serum for massive chylomicronemia, triglycerides, cholesterol and lipoprotein electrophoresis (by the cellulose acetate method). Lipoprotein testing results showed 12 patients with Type II A or II B and 8 patients with Type IV abnormalities. No Types I, III or V were found. These 20 patients represent a lower number of hyperlipoproteinemic patients than would be expected in the general population."}
{"id": "PMID:207212", "title": "Synovial sarcoma of the hypopharynx.", "content": "Primary synovial sarcoma of the hypopharynx is an extremely rare neoplasm. Only 16 cases could be traced in the literature so far. An additional case, in a 29-year-old male patient, is presented. Progressive disturbance of deglutition and speech, chocking sensation, and mild respiratory distress were his original complaints. Our case differs from those previously reported in that a) the tumor was pedunculated, and the site of its attachment could be very well-defined, and b) unusual intratumoral destructive hemorrhage turned the case into an emergency. The pedicle was radically excised together with part of the grossly uninvolved underlying tissue, and the tumor was removed in toto. The histological findings are described. The patient is under observation. No recurrence has been noticed 11 months after surgery, and there are no signs of metastasis. The origin of the tumor and its treatment are discussed.", "contents": "Synovial sarcoma of the hypopharynx. Primary synovial sarcoma of the hypopharynx is an extremely rare neoplasm. Only 16 cases could be traced in the literature so far. An additional case, in a 29-year-old male patient, is presented. Progressive disturbance of deglutition and speech, chocking sensation, and mild respiratory distress were his original complaints. Our case differs from those previously reported in that a) the tumor was pedunculated, and the site of its attachment could be very well-defined, and b) unusual intratumoral destructive hemorrhage turned the case into an emergency. The pedicle was radically excised together with part of the grossly uninvolved underlying tissue, and the tumor was removed in toto. The histological findings are described. The patient is under observation. No recurrence has been noticed 11 months after surgery, and there are no signs of metastasis. The origin of the tumor and its treatment are discussed."}
{"id": "PMID:207220", "title": "[Inorganic polyphosphate metabolism in Staphylococcus aureus and the action on it of antibiotics].", "content": "The culure of Staph. aureus in the exponential growth phase contained 14-18 mg/g of dry orthophosphate biomass and 18-22 mg/g of dry acid insoluble polyphosphate biomass. The extracellular extract of the culture had a phosphohydrolase activity with respect to high molecular polyphosphates, tripolyphosphate and pyrophosphate. Penicillin and bacitracin which inhibited the biosynthesis of the cell wall had no effect on the content of polyphosphates and the phosphohydrolase activity of Staph. aureus. Heliomycin which inhibited the biosynthesis of RNA increased the content of polyphosphates by 1.5 times and decreased the content of ATP by 30 per cent in the cells of Staph. aureus.", "contents": "[Inorganic polyphosphate metabolism in Staphylococcus aureus and the action on it of antibiotics]. The culure of Staph. aureus in the exponential growth phase contained 14-18 mg/g of dry orthophosphate biomass and 18-22 mg/g of dry acid insoluble polyphosphate biomass. The extracellular extract of the culture had a phosphohydrolase activity with respect to high molecular polyphosphates, tripolyphosphate and pyrophosphate. Penicillin and bacitracin which inhibited the biosynthesis of the cell wall had no effect on the content of polyphosphates and the phosphohydrolase activity of Staph. aureus. Heliomycin which inhibited the biosynthesis of RNA increased the content of polyphosphates by 1.5 times and decreased the content of ATP by 30 per cent in the cells of Staph. aureus."}
{"id": "PMID:207221", "title": "Practical method for detecting poliovirus in anaerobic digester sludge.", "content": "A method has been developed which permits reliable detection of low numbers of poliovirus infective units in anaerobic digester sludge and dewatered composted sludge.", "contents": "Practical method for detecting poliovirus in anaerobic digester sludge. A method has been developed which permits reliable detection of low numbers of poliovirus infective units in anaerobic digester sludge and dewatered composted sludge."}
{"id": "PMID:207227", "title": "Primary versus secondary nerve repair: a review of the literature.", "content": "The pros and cons of primary and secondary neurorrhaphy are discussed on the basis of a study of the literature. The impression is gained that recently, many surgeons have come to prefer secondary restoration of the continuity of a severed peripheral nerve. However, the longer the delay, the more serious the problems and the worse the prognosis. The authors conclude therefore that repair of the nerve in the earliest possible stage should always be attempted. Provided the relevant conditions are fulfilled, primary neurorrhaphy should be seriously considered; the prognosis of primary repair is good, especially in children. If primary neurorrhaphy is contra-indicated, early secondary repair is to be preferred to further delay.", "contents": "Primary versus secondary nerve repair: a review of the literature. The pros and cons of primary and secondary neurorrhaphy are discussed on the basis of a study of the literature. The impression is gained that recently, many surgeons have come to prefer secondary restoration of the continuity of a severed peripheral nerve. However, the longer the delay, the more serious the problems and the worse the prognosis. The authors conclude therefore that repair of the nerve in the earliest possible stage should always be attempted. Provided the relevant conditions are fulfilled, primary neurorrhaphy should be seriously considered; the prognosis of primary repair is good, especially in children. If primary neurorrhaphy is contra-indicated, early secondary repair is to be preferred to further delay."}
{"id": "PMID:207228", "title": "Ultrastructure and x-ray microanalysis of siderosome.", "content": "Comparative ultrastructural examination and energy-dispersive electron probe X-ray microanalysis were performed on a long standing skin lesion of hemosiderotic histiocytoma. Iron-containing fine particles present in siderosome were the main element of interest. Qualitative study of spectra over the siderosomes clearly demonstrated the characteristic X-ray energy emitted by iron, whereas spectra obtained from adjacent cytoplasm revealed minimal iron peak. On quantitative evaluation of the spectra yielded from various siderosomes, iron counts intensity was found to be proportionally increased with increment in amount and electron opacity of the siderosomal inclusion. Accounts on chemical nature of the siderosomal inclusion and on the presence of lipid residue in cytoplasms were noted.", "contents": "Ultrastructure and x-ray microanalysis of siderosome. Comparative ultrastructural examination and energy-dispersive electron probe X-ray microanalysis were performed on a long standing skin lesion of hemosiderotic histiocytoma. Iron-containing fine particles present in siderosome were the main element of interest. Qualitative study of spectra over the siderosomes clearly demonstrated the characteristic X-ray energy emitted by iron, whereas spectra obtained from adjacent cytoplasm revealed minimal iron peak. On quantitative evaluation of the spectra yielded from various siderosomes, iron counts intensity was found to be proportionally increased with increment in amount and electron opacity of the siderosomal inclusion. Accounts on chemical nature of the siderosomal inclusion and on the presence of lipid residue in cytoplasms were noted."}
{"id": "PMID:207229", "title": "[Multivesicular vacuolization in malignant histiocytoma of the skin (author's transl].", "content": "A 47-year-old patient developed several rapidly growing tumours in his right leg. Histiologic and electron microscopic examination revealed morphological characteristics suggesting the histiocytic origin of the tumour cells. An important finding was the striking number of pleomorphic membraneous inclusions and large vacuoles containing numerous small vesicles. These cytoplasmic inclusions are interpreted as transformed multivesicular bodies. Their formation may be an expression of an increased and bizarre membraneous activity of a malignant cell race. Radiotherapy resulted in a remarkable rapid and complete remission.", "contents": "[Multivesicular vacuolization in malignant histiocytoma of the skin (author's transl]. A 47-year-old patient developed several rapidly growing tumours in his right leg. Histiologic and electron microscopic examination revealed morphological characteristics suggesting the histiocytic origin of the tumour cells. An important finding was the striking number of pleomorphic membraneous inclusions and large vacuoles containing numerous small vesicles. These cytoplasmic inclusions are interpreted as transformed multivesicular bodies. Their formation may be an expression of an increased and bizarre membraneous activity of a malignant cell race. Radiotherapy resulted in a remarkable rapid and complete remission."}
{"id": "PMID:207232", "title": "\"Total\" therapy for small cell carcinoma of the lung.", "content": "Seventy-one consecutive patients with small cell carcinoma of the lung were treated with an integrated approach between November, 1974, and May, 1977. The regimen included radiotherapy to the primary site, relatively brief (6 to 12 weeks) although intensive chemotherapy, and prophylactic cranial irradiation. Complete responses were achieved in 75% and 40% of patients with limited and extensive disease, respectively. Modest prolongation of survival (median, 10 months) was realized by patients with extensive disease, but prolonged relapse-free survival was not observed. In contrast, one-half of the patients with limited disease who achieved a complete response have remained clinically free of disease without further treatment for a mean of 18 months (range, 6 to 33 months). Since all relapses to date have been noted within the first year following cessation of treatment, this experience suggests there may be a potential for cure in those survivors who are now relapse free for intervals exceeding two years.", "contents": "\"Total\" therapy for small cell carcinoma of the lung. Seventy-one consecutive patients with small cell carcinoma of the lung were treated with an integrated approach between November, 1974, and May, 1977. The regimen included radiotherapy to the primary site, relatively brief (6 to 12 weeks) although intensive chemotherapy, and prophylactic cranial irradiation. Complete responses were achieved in 75% and 40% of patients with limited and extensive disease, respectively. Modest prolongation of survival (median, 10 months) was realized by patients with extensive disease, but prolonged relapse-free survival was not observed. In contrast, one-half of the patients with limited disease who achieved a complete response have remained clinically free of disease without further treatment for a mean of 18 months (range, 6 to 33 months). Since all relapses to date have been noted within the first year following cessation of treatment, this experience suggests there may be a potential for cure in those survivors who are now relapse free for intervals exceeding two years."}
{"id": "PMID:207234", "title": "[Ultrastructure and clinicopathological aspects of mucoepidermoid tumour of the salivary glands (author's transl)].", "content": "The mucoepidermoid tumor of the salivary glands is relatively rare; its ultrastructure is analysed on the basis of four cases. Three secretory tumour cells can be differentiated: one tumour cell with mucous secretion and two tumour cells with abortive secretion which are different in structure. The dysregulated and abortive secretion is due to a defective functional differentiation and defective innervation of tumour cells. Further characteristic tumour cells without secretion are: epidermoid cells, myoepithelial cells and clear cells. The variety of the tumour cells in the tissue is due to the broad cytogenic prospection of acinar and tubular epithelium of the salivary glands. Recommendations are given for practical electron-microscopic diagnosis by means of typical leading elements of the structure. The author tries to assess the gravity of the mucoepidermoid tumour by ultramicroscopic findings. The tumour is classified as potentially malignant. Therapeutic aspects are discussed dependent upon this grading.", "contents": "[Ultrastructure and clinicopathological aspects of mucoepidermoid tumour of the salivary glands (author's transl)]. The mucoepidermoid tumor of the salivary glands is relatively rare; its ultrastructure is analysed on the basis of four cases. Three secretory tumour cells can be differentiated: one tumour cell with mucous secretion and two tumour cells with abortive secretion which are different in structure. The dysregulated and abortive secretion is due to a defective functional differentiation and defective innervation of tumour cells. Further characteristic tumour cells without secretion are: epidermoid cells, myoepithelial cells and clear cells. The variety of the tumour cells in the tissue is due to the broad cytogenic prospection of acinar and tubular epithelium of the salivary glands. Recommendations are given for practical electron-microscopic diagnosis by means of typical leading elements of the structure. The author tries to assess the gravity of the mucoepidermoid tumour by ultramicroscopic findings. The tumour is classified as potentially malignant. Therapeutic aspects are discussed dependent upon this grading."}
{"id": "PMID:207235", "title": "Quantitative nuclear-cytoplasmic ratios in human hepatomas.", "content": "This report presents quantitative data on nuclear-cytoplasmic (N/C) ratios of human hepatomas, normal liver specimens, and cirrhotic liver specimens. The N/C ratios were determined by point-counting, using an intraocular microscopic grid as the source of the points. The N/C ratios of hepatoma cells were chiefly greater than 0.21, while those of normal and cirrhotic liver cells were chiefly less than 0.21. The N/C ratios of hepatoma cells had a variance significantly greater than those of normal and cirrhotic cells. Quantitative N/C ratios can yield information useful in characterizing cell types for diagnostic purposes.", "contents": "Quantitative nuclear-cytoplasmic ratios in human hepatomas. This report presents quantitative data on nuclear-cytoplasmic (N/C) ratios of human hepatomas, normal liver specimens, and cirrhotic liver specimens. The N/C ratios were determined by point-counting, using an intraocular microscopic grid as the source of the points. The N/C ratios of hepatoma cells were chiefly greater than 0.21, while those of normal and cirrhotic liver cells were chiefly less than 0.21. The N/C ratios of hepatoma cells had a variance significantly greater than those of normal and cirrhotic cells. Quantitative N/C ratios can yield information useful in characterizing cell types for diagnostic purposes."}
{"id": "PMID:207236", "title": "Metastatic tumors of the endocardium: report of three cases.", "content": "Because of their apparent rarity and the tendency of clinicians to lump indicative signs and symptoms under the heading of metastatic disease, metastatic tumors of the endocardium are seldom mentioned in the literature, in the three cases presented herein, endocardial metastases were evident at autopsy. In one case of malignant melanoma, clinical evidence for endocardial involvement was present in life. This article also presents a case of endocardial involvement by Wilms' tumor and a case of endocardial involvement by hypernephroma with pulmonry tumor emboli.", "contents": "Metastatic tumors of the endocardium: report of three cases. Because of their apparent rarity and the tendency of clinicians to lump indicative signs and symptoms under the heading of metastatic disease, metastatic tumors of the endocardium are seldom mentioned in the literature, in the three cases presented herein, endocardial metastases were evident at autopsy. In one case of malignant melanoma, clinical evidence for endocardial involvement was present in life. This article also presents a case of endocardial involvement by Wilms' tumor and a case of endocardial involvement by hypernephroma with pulmonry tumor emboli."}
{"id": "PMID:207238", "title": "Cystosarcoma phyllodes in young women.", "content": "A total of eight cases of cystosarcoma phyllodes in women under 25 years of age were reported to the Swedish Cancer Registry during a ten-year period (1960 to 1969). Only one of these tumors was malignant. It was successfully treated with simple mastectomy and postoperative radiation therapy. Of the remaining seven cases, six were treated with local excision of the lesion and one with simple mastectomy. In no case, did the tumor recur during a follow-up of an average of ten years. Local excision seems to be sufficient for the benign form of the tumor, whereas simple mastectomy is indicated for the malignant form. Radical mastectomy is indicated only of the tumor has invaded the pectoral fascia. The tumor rarely metastasizes to the axillary lymph nodes.", "contents": "Cystosarcoma phyllodes in young women. A total of eight cases of cystosarcoma phyllodes in women under 25 years of age were reported to the Swedish Cancer Registry during a ten-year period (1960 to 1969). Only one of these tumors was malignant. It was successfully treated with simple mastectomy and postoperative radiation therapy. Of the remaining seven cases, six were treated with local excision of the lesion and one with simple mastectomy. In no case, did the tumor recur during a follow-up of an average of ten years. Local excision seems to be sufficient for the benign form of the tumor, whereas simple mastectomy is indicated for the malignant form. Radical mastectomy is indicated only of the tumor has invaded the pectoral fascia. The tumor rarely metastasizes to the axillary lymph nodes."}
{"id": "PMID:207240", "title": "Isolation of a variant of BK virus with altered restriction endonuclease pattern.", "content": "A papovavirus was isolated from the urine of a 24 year old female who underwent bone marrow transplantation after a relapse of acute myeloid leukemia. The virus (JL) resembles BK virus in its antigenic and growth properties, but has a different restriction endonuclease pattern after digestion with the restriction endonucleases Eco R1 and R Hind II + III.", "contents": "Isolation of a variant of BK virus with altered restriction endonuclease pattern. A papovavirus was isolated from the urine of a 24 year old female who underwent bone marrow transplantation after a relapse of acute myeloid leukemia. The virus (JL) resembles BK virus in its antigenic and growth properties, but has a different restriction endonuclease pattern after digestion with the restriction endonucleases Eco R1 and R Hind II + III."}
{"id": "PMID:207241", "title": "Stability of neurotropic mouse hepatitis virus (JHM strain) during chronic infection of neuroblastoma cells.", "content": "A line of mouse neuroblastoma cells which was chronically infected with the neurotropic strain (JHM) of MHV, a member of the coronavirus group, was established. These cells, designated NJ, exhibited typical MHV cytopathic effects (CPE) at all passage levels along with the continual production of infectious virus. Most cells were positive for viral antigen by immunoflourescence. Viral particles consistent with the morphology of MHV were found by electron microscopy. The uninfected neuroblastoma cell line did not contain a detectable population of cells resistant to JHM, and persistence did not elicit the production of interferon. No plaque morphology or temperature sensitive mutants were selected for in the NJ culture, and we were unable to detect the presence of either a defective or defective interfering virus population. The addition of low concentration antiviral antibody modulated the infection to a carrier culture with viral antigen in the cytoplasm of the cells, but no infectious virus was produced, and the cells lacked both surface viral antigen and CPE. Possible mechanisms of viral persistence in vitro are discussed.", "contents": "Stability of neurotropic mouse hepatitis virus (JHM strain) during chronic infection of neuroblastoma cells. A line of mouse neuroblastoma cells which was chronically infected with the neurotropic strain (JHM) of MHV, a member of the coronavirus group, was established. These cells, designated NJ, exhibited typical MHV cytopathic effects (CPE) at all passage levels along with the continual production of infectious virus. Most cells were positive for viral antigen by immunoflourescence. Viral particles consistent with the morphology of MHV were found by electron microscopy. The uninfected neuroblastoma cell line did not contain a detectable population of cells resistant to JHM, and persistence did not elicit the production of interferon. No plaque morphology or temperature sensitive mutants were selected for in the NJ culture, and we were unable to detect the presence of either a defective or defective interfering virus population. The addition of low concentration antiviral antibody modulated the infection to a carrier culture with viral antigen in the cytoplasm of the cells, but no infectious virus was produced, and the cells lacked both surface viral antigen and CPE. Possible mechanisms of viral persistence in vitro are discussed."}
{"id": "PMID:207242", "title": "Interferon production and activity in mouse neuroblastoma cells.", "content": "Mouse neuroblastoma cells are capable of synthesizing interferon after induction with virus or polynucleotides. Differentiation of neuroblastoma cells depresses interferon synthesis without an apparent effect on sensitivity to interferon.", "contents": "Interferon production and activity in mouse neuroblastoma cells. Mouse neuroblastoma cells are capable of synthesizing interferon after induction with virus or polynucleotides. Differentiation of neuroblastoma cells depresses interferon synthesis without an apparent effect on sensitivity to interferon."}
{"id": "PMID:207243", "title": "[Value of electroencephalographic findings in the prognosis of Lennox-Gastaut syndrome].", "content": "The electroencephalographic findings observed in twenty-nine patients with Lennox-Gastaut syndrome were related with prognosis of the epileptic manifestations. The presence of slow spike-wave complexes with preponderance of spike over the slow wave and the presence of fixed complexes in spite of the medical treatment, are related with poor prognosis for the epileptic manifestations.", "contents": "[Value of electroencephalographic findings in the prognosis of Lennox-Gastaut syndrome]. The electroencephalographic findings observed in twenty-nine patients with Lennox-Gastaut syndrome were related with prognosis of the epileptic manifestations. The presence of slow spike-wave complexes with preponderance of spike over the slow wave and the presence of fixed complexes in spite of the medical treatment, are related with poor prognosis for the epileptic manifestations."}
{"id": "PMID:207244", "title": "[Radicular syndrome caused by epidural tuberculous granuloma. Case report].", "content": "A case of tuberculous granuloma producing a radicular syndrome in a 58 year-old white male is reported. Excision of the granuloma and the administration of antituberculous therapy was followed by complete recovery.", "contents": "[Radicular syndrome caused by epidural tuberculous granuloma. Case report]. A case of tuberculous granuloma producing a radicular syndrome in a 58 year-old white male is reported. Excision of the granuloma and the administration of antituberculous therapy was followed by complete recovery."}
{"id": "PMID:207245", "title": "Hypersomnia-sleep apnea due to micrognathia. Reversal by tracheoplasty.", "content": "A 67-year-old woman with acquired micrognathia developed severe daytime hypersomnia, loud snoring, nocturnal enuresis, encopresis, and hypertension. A polysomnogram demonstrated 564 sleep apneas, primarily obstructive, recurrent hypoxia, a bradytachycardia, and absent stages III, IV, and REM sleep. Endoscopy during sleep revealed recurrent active closure of the upper pharynx associated with loud snoring. A tracheoplasty was done because of severity of symptoms and failure of conservative therapy. Dramatic improvement in sleepiness and hypertension occurred within 48 hours. On postoperative night 15 a repeated polysomnogram showed only 23 apneas, no hypoxia or bradytachycardia, and long periods of stage II, IV, and REM sleep. Patients with the hypersomnia-sleep apnea syndrome should be provided with a tracheal opening during sleep when severe daytime somnolence, cardiac arrhythmias, and hypertension are present.", "contents": "Hypersomnia-sleep apnea due to micrognathia. Reversal by tracheoplasty. A 67-year-old woman with acquired micrognathia developed severe daytime hypersomnia, loud snoring, nocturnal enuresis, encopresis, and hypertension. A polysomnogram demonstrated 564 sleep apneas, primarily obstructive, recurrent hypoxia, a bradytachycardia, and absent stages III, IV, and REM sleep. Endoscopy during sleep revealed recurrent active closure of the upper pharynx associated with loud snoring. A tracheoplasty was done because of severity of symptoms and failure of conservative therapy. Dramatic improvement in sleepiness and hypertension occurred within 48 hours. On postoperative night 15 a repeated polysomnogram showed only 23 apneas, no hypoxia or bradytachycardia, and long periods of stage II, IV, and REM sleep. Patients with the hypersomnia-sleep apnea syndrome should be provided with a tracheal opening during sleep when severe daytime somnolence, cardiac arrhythmias, and hypertension are present."}
{"id": "PMID:207248", "title": "Central retinal artery occlusion complicating Fabry's disease.", "content": "A 16-year-old boy had a central retinal artery occlusion and was subsequently diagnosed as a hemizygote with Fabry's disease. The typical ocular manifestations in males with this inborn error of glycosphingolipid metabolism include whorl-like corneal epithelial infiltrates, retinal and conjunctival vessel tortuosity, and lenticular changes. The present case represents the first report of a retinal artery occlusion as an ocular complication of Fabry's disease.", "contents": "Central retinal artery occlusion complicating Fabry's disease. A 16-year-old boy had a central retinal artery occlusion and was subsequently diagnosed as a hemizygote with Fabry's disease. The typical ocular manifestations in males with this inborn error of glycosphingolipid metabolism include whorl-like corneal epithelial infiltrates, retinal and conjunctival vessel tortuosity, and lenticular changes. The present case represents the first report of a retinal artery occlusion as an ocular complication of Fabry's disease."}
{"id": "PMID:207249", "title": "Fibrous histiocytoma metastatic to the orbit.", "content": "The term fibrous histiocytoma encompasses a heterogenous group of tumors believed to have a common origin in the histiocyte. These tumors demonstrate a wide histopathologic spectrum ranging from a predominantly cellular to a predominantly fibrous pattern. No clinical or histological criteria have been identified that can predict malignant behavior. Although generally characterized by local recurrence, a metastatic potential does exist. Fibrous histiocytoma of the thigh metastasized to the orbit.", "contents": "Fibrous histiocytoma metastatic to the orbit. The term fibrous histiocytoma encompasses a heterogenous group of tumors believed to have a common origin in the histiocyte. These tumors demonstrate a wide histopathologic spectrum ranging from a predominantly cellular to a predominantly fibrous pattern. No clinical or histological criteria have been identified that can predict malignant behavior. Although generally characterized by local recurrence, a metastatic potential does exist. Fibrous histiocytoma of the thigh metastasized to the orbit."}
{"id": "PMID:207250", "title": "Treatment of herpes simplex keratitis with levamisole.", "content": "A model of chronic herpetic keratitis was developed by injecting rabbits subconjunctivally with a corticosteroid. A levamisole hydrochloride-treated group of these rabbits developed milder, more rapidly healing epithelial lesions than an untreated group. Although most of the untreated rabbits developed stromal disease, almost all of the lesions in the levamisole-treated animals were limited to the epithelium.", "contents": "Treatment of herpes simplex keratitis with levamisole. A model of chronic herpetic keratitis was developed by injecting rabbits subconjunctivally with a corticosteroid. A levamisole hydrochloride-treated group of these rabbits developed milder, more rapidly healing epithelial lesions than an untreated group. Although most of the untreated rabbits developed stromal disease, almost all of the lesions in the levamisole-treated animals were limited to the epithelium."}
{"id": "PMID:207251", "title": "Transmission of a mucosal disease virus infection between sheep.", "content": "The transmission of mucosal disease virus (MDV) from infected ewes and their lambs to susceptible sheep was investigated. MDV was recovered from the amniotic fluid of an infected pregnant ewe and from the blood, nasal swabs and urine of hairy lambs. MDV infection was transmitted either at lambing, from infective foetal fluids or lambs, or later as a result of contact with a surviving with a hairy lamb and either aborted or gave birth to an infected hairy lamb. Adult sheep and 12-months-old sheep were less readily infected than were newborn lambs. Pregnant ewes were infected by contact with a hairy lamb and either aborted or gave birth to an infected hairy lamb. A method to minimise spread of the infection in the field is suggested.", "contents": "Transmission of a mucosal disease virus infection between sheep. The transmission of mucosal disease virus (MDV) from infected ewes and their lambs to susceptible sheep was investigated. MDV was recovered from the amniotic fluid of an infected pregnant ewe and from the blood, nasal swabs and urine of hairy lambs. MDV infection was transmitted either at lambing, from infective foetal fluids or lambs, or later as a result of contact with a surviving with a hairy lamb and either aborted or gave birth to an infected hairy lamb. Adult sheep and 12-months-old sheep were less readily infected than were newborn lambs. Pregnant ewes were infected by contact with a hairy lamb and either aborted or gave birth to an infected hairy lamb. A method to minimise spread of the infection in the field is suggested."}
{"id": "PMID:207252", "title": "Epidemic adenovirus inclusions body hepatitis of the chicken in Australia.", "content": "The occurrence of inclusion body hepatitis (IBH) on 11 properties in Australia is described. The 6 Victorian cases occurred between 1967 and 1973 and were identified as incidental findings accompanying other diseases or occurred as ill-defined, minor economic disease episodes. In well-managed flocks the extra mortality attributable to IBH was as low as 1.8% which represented a 50% increase in total mortality. The 1973 epidemic in New South Wales on 5 related farms resulted in flock mortality of 8.4% to 32.3% and an average mortality of 19.5% of 814,000 birds. For uninfected flocks of 307,000 birds the average mortality was 8.5%. Higher mortality in male flocks was statistically highly significant as was lowered efficiency of feed conversion. Growth rate in both sexes was depressed by about 0.15 kg in 70 days and heavy downgrading at processing occurred. Secondary infections were important. The cardinal features of IBH were fatal necrotising hepatitis with Cowdry type-A intranuclear inclusion body formation; secondary bacterial infections were also important causes of loss.", "contents": "Epidemic adenovirus inclusions body hepatitis of the chicken in Australia. The occurrence of inclusion body hepatitis (IBH) on 11 properties in Australia is described. The 6 Victorian cases occurred between 1967 and 1973 and were identified as incidental findings accompanying other diseases or occurred as ill-defined, minor economic disease episodes. In well-managed flocks the extra mortality attributable to IBH was as low as 1.8% which represented a 50% increase in total mortality. The 1973 epidemic in New South Wales on 5 related farms resulted in flock mortality of 8.4% to 32.3% and an average mortality of 19.5% of 814,000 birds. For uninfected flocks of 307,000 birds the average mortality was 8.5%. Higher mortality in male flocks was statistically highly significant as was lowered efficiency of feed conversion. Growth rate in both sexes was depressed by about 0.15 kg in 70 days and heavy downgrading at processing occurred. Secondary infections were important. The cardinal features of IBH were fatal necrotising hepatitis with Cowdry type-A intranuclear inclusion body formation; secondary bacterial infections were also important causes of loss."}
{"id": "PMID:207257", "title": "The pathogenesis of infectious avian encephalomyelitis. 1. The effect of the age of the chicken and the route of administration of the virus.", "content": "The age of the chicken at the time of infection with infectious avian encephalomyelitis virus (IAEV) and the route of the administration of the virus had a marked effect on the development of the clinical disease. Chickens given the virus by intramuscular, intraperitoneal and oral routes exhibited a decreased susceptibility to development of clinical disease with increasing age. Irrespective of age, chickens were consistently susceptible to intracerebral inoculation of IAEV. Chickens infected with the virus at 1-, 7- and 14-days of age developed lower neutralising antibody titres to IAEV than chickens infected at 21 and 28 days. A relationship between the ability to produce specific neutralising antibody to IAEV and susceptibility to the development of clinical disease is discussed.", "contents": "The pathogenesis of infectious avian encephalomyelitis. 1. The effect of the age of the chicken and the route of administration of the virus. The age of the chicken at the time of infection with infectious avian encephalomyelitis virus (IAEV) and the route of the administration of the virus had a marked effect on the development of the clinical disease. Chickens given the virus by intramuscular, intraperitoneal and oral routes exhibited a decreased susceptibility to development of clinical disease with increasing age. Irrespective of age, chickens were consistently susceptible to intracerebral inoculation of IAEV. Chickens infected with the virus at 1-, 7- and 14-days of age developed lower neutralising antibody titres to IAEV than chickens infected at 21 and 28 days. A relationship between the ability to produce specific neutralising antibody to IAEV and susceptibility to the development of clinical disease is discussed."}
{"id": "PMID:207258", "title": "The pathogenesis of infectious avian encephalomyelitis. 2. The effect of immunosuppression on the disease.", "content": "Normal chickens given infectious avian encephalomyelitis virus (IAEV) orally at 1, 7 or 14 days of age developed infectious avian encephalomyelitis (IAE), whereas those dosed with the virus at 21, 28 and 35 days of age did not. Chickens in all of these age groups that had been treated with cyclophosphamide or testosterone developed clinical IAE. Intraperitoneal inoculation of IAEV immunoglobulin at the time of dosing with the virus, or 48 hours later, protected normal and immunosuppressed chickens against the onset of clinical IAE. The titre of IAEV serum neutralising antibody was found to be lower in normal chickens given the virus at 1, 7 and 14 days of age in older chickens. These results suggest a significant role for the humoral immune system in the pathogenesis of IAE and in the development of immunity to the disease.", "contents": "The pathogenesis of infectious avian encephalomyelitis. 2. The effect of immunosuppression on the disease. Normal chickens given infectious avian encephalomyelitis virus (IAEV) orally at 1, 7 or 14 days of age developed infectious avian encephalomyelitis (IAE), whereas those dosed with the virus at 21, 28 and 35 days of age did not. Chickens in all of these age groups that had been treated with cyclophosphamide or testosterone developed clinical IAE. Intraperitoneal inoculation of IAEV immunoglobulin at the time of dosing with the virus, or 48 hours later, protected normal and immunosuppressed chickens against the onset of clinical IAE. The titre of IAEV serum neutralising antibody was found to be lower in normal chickens given the virus at 1, 7 and 14 days of age in older chickens. These results suggest a significant role for the humoral immune system in the pathogenesis of IAE and in the development of immunity to the disease."}
{"id": "PMID:207259", "title": "The pathogenesis of infectious avian encephalomyelitis. 3. The relationship between viraemia, invasion of the brain by the virus, and the development of specific serum neutralising antibody.", "content": "An association was demonstrated between the development of clinical infectious avian encephalomyelitis (IAE), the persistence and titre of infectious avian encephalomyelitis virus (IAEV) in the brain of the chicken, the duration of detectable viraemia and the age of the chicken at the time of infection with the virus. The older the chicken at the time of infection the milder the disease, the lower the virus titre in the brain and the shorter the period of viraemia. IAEV serum neutralising antibody was produced earlier after infection in older chickens, and its detection was associated with decreasing virus titres in the brain and the cessation of detectable viraemia. Treatment of chickens with testosterone in ova, to inhibit the development of antibody synthesis, prevented the onset of age-associated resistance and testosterone treated birds were as susceptible to clinical IAE as baby chickens. The results suggested that the ability to produce IAEV serum neutralising antibody was an important component of age-associated resistance to IAE.", "contents": "The pathogenesis of infectious avian encephalomyelitis. 3. The relationship between viraemia, invasion of the brain by the virus, and the development of specific serum neutralising antibody. An association was demonstrated between the development of clinical infectious avian encephalomyelitis (IAE), the persistence and titre of infectious avian encephalomyelitis virus (IAEV) in the brain of the chicken, the duration of detectable viraemia and the age of the chicken at the time of infection with the virus. The older the chicken at the time of infection the milder the disease, the lower the virus titre in the brain and the shorter the period of viraemia. IAEV serum neutralising antibody was produced earlier after infection in older chickens, and its detection was associated with decreasing virus titres in the brain and the cessation of detectable viraemia. Treatment of chickens with testosterone in ova, to inhibit the development of antibody synthesis, prevented the onset of age-associated resistance and testosterone treated birds were as susceptible to clinical IAE as baby chickens. The results suggested that the ability to produce IAEV serum neutralising antibody was an important component of age-associated resistance to IAE."}
{"id": "PMID:207260", "title": "The pathogenesis of infectious avian encephalomyelitis. 4. The effect of maternal antibody on the development of the disease.", "content": "Infectious avian encephalomyelitis virus (IAEV) maternal antibody was detected in the serum of chickens for up to 21 days following hatching. This antibody protected chickens against clinical IAE after intracerebral inoculation with van Roekel strain or oral administration of the NSW-1 strain of IAEV. Maternal antibody to IAEV also protected testosterone bursectomised chickens against the development of clinical disease. IAEV maternal antibody also influeced the pattern of virus excretion in faeces and serological responsiveness. This influence on antibody responses persisted beyond the time that IAEV maternal antibody could be detected. The importance of IAEV maternal antibody on the strategy of vaccination against IAE is discussed.", "contents": "The pathogenesis of infectious avian encephalomyelitis. 4. The effect of maternal antibody on the development of the disease. Infectious avian encephalomyelitis virus (IAEV) maternal antibody was detected in the serum of chickens for up to 21 days following hatching. This antibody protected chickens against clinical IAE after intracerebral inoculation with van Roekel strain or oral administration of the NSW-1 strain of IAEV. Maternal antibody to IAEV also protected testosterone bursectomised chickens against the development of clinical disease. IAEV maternal antibody also influeced the pattern of virus excretion in faeces and serological responsiveness. This influence on antibody responses persisted beyond the time that IAEV maternal antibody could be detected. The importance of IAEV maternal antibody on the strategy of vaccination against IAE is discussed."}
{"id": "PMID:207261", "title": "Lack of protection against oxygen toxicity by in vivo protective agents in the isolated toad bladder.", "content": "Agents which protect against the development of oxygen toxicity in vivo were tested in an in vitro system, the isolated urinary bladder of the toad Bufo marinus. None of the agents protected against the inhibition of sodium transport across the bladder by hyperbaric oxygen exposure. Two protective agents, disulfiram and diethyldithiocarbamic acid, significantly increased the rate and extent of sodium transport inhibition by 5 ATA of oxygen, either when added in vitro or given in vivo. It was concluded that oxygen toxicity protective agents may have a nonspecific action in vivo.", "contents": "Lack of protection against oxygen toxicity by in vivo protective agents in the isolated toad bladder. Agents which protect against the development of oxygen toxicity in vivo were tested in an in vitro system, the isolated urinary bladder of the toad Bufo marinus. None of the agents protected against the inhibition of sodium transport across the bladder by hyperbaric oxygen exposure. Two protective agents, disulfiram and diethyldithiocarbamic acid, significantly increased the rate and extent of sodium transport inhibition by 5 ATA of oxygen, either when added in vitro or given in vivo. It was concluded that oxygen toxicity protective agents may have a nonspecific action in vivo."}
{"id": "PMID:207262", "title": "Haemichrome formation from haemoglobin subunits by hydrogen peroxide.", "content": "The effect of H2O2 on ferrous human haemoglobin subunits (alphash-, betash-, alphapmb- and betapmb-chains) was studied. These chains were easily transformed to haemichrome by the addition of H2O2 or H2O2-generating systems, including glucose oxidase (EC 1.1.3.4) AND XANTHINE OXIDASE (EC 1.2.3.2), and this was ascertained by e.p.r. measurements and by absorption spectra. The changes in these haemoglobin subunits were not inhibited by superoxide dismutase (EC 1.15.1.1), but were decreased by catalase (EC 1.11.1.6). The rate of oxidation of alphapmb-chains was higher than that of alphash-chains, and the rate of oxidation of betapmb-chains was higher than that of betash-chains. Haemichrome was demonstrated to be formed directly from these ferrous chains by the attack by H2O2, and this process did not involve formation of methaemoglobin. On the basis of these findings the kinetics of the reaction between the haemoglobin subunits and H2O2 was studied, and the pathological significance of H2O2 in disorders of erythrocytes such as thalassaemia was discussed.", "contents": "Haemichrome formation from haemoglobin subunits by hydrogen peroxide. The effect of H2O2 on ferrous human haemoglobin subunits (alphash-, betash-, alphapmb- and betapmb-chains) was studied. These chains were easily transformed to haemichrome by the addition of H2O2 or H2O2-generating systems, including glucose oxidase (EC 1.1.3.4) AND XANTHINE OXIDASE (EC 1.2.3.2), and this was ascertained by e.p.r. measurements and by absorption spectra. The changes in these haemoglobin subunits were not inhibited by superoxide dismutase (EC 1.15.1.1), but were decreased by catalase (EC 1.11.1.6). The rate of oxidation of alphapmb-chains was higher than that of alphash-chains, and the rate of oxidation of betapmb-chains was higher than that of betash-chains. Haemichrome was demonstrated to be formed directly from these ferrous chains by the attack by H2O2, and this process did not involve formation of methaemoglobin. On the basis of these findings the kinetics of the reaction between the haemoglobin subunits and H2O2 was studied, and the pathological significance of H2O2 in disorders of erythrocytes such as thalassaemia was discussed."}
{"id": "PMID:207263", "title": "Neutral metallo-proteinases of rabbit bone. Separation in latent forms of distinct enzymes that when activated degrade collagen, gelatin and proteoglycans.", "content": "Rabbit bones in culture produce specific collagenase and neutral metallo-proteinase activity in latent forms that can be activated by either 4-aminophenylmercuric acetate or trypsin. Latent neutral metallo-proteinase activity was resolved by gel filtration into two enzymes, distinct from collagenase, that degrade gelatin and cartilage proteoglycans.", "contents": "Neutral metallo-proteinases of rabbit bone. Separation in latent forms of distinct enzymes that when activated degrade collagen, gelatin and proteoglycans. Rabbit bones in culture produce specific collagenase and neutral metallo-proteinase activity in latent forms that can be activated by either 4-aminophenylmercuric acetate or trypsin. Latent neutral metallo-proteinase activity was resolved by gel filtration into two enzymes, distinct from collagenase, that degrade gelatin and cartilage proteoglycans."}
{"id": "PMID:207264", "title": "The temperature-dependence of the loss of latency of lysosomal enzymes.", "content": "1. When Triton-filled lysosomes from rat liver are incubated for up to 50min at 37 degrees C, pH7.4, in 0.25m-sucrose, no loss of latency of N-acetyl-beta-glucosaminidase or p-nitrophenyl phosphatase occurs unless the incubated lysosomes are cooled to approx. 15 degrees C. 2. It is suggested that a phase change takes place in the incubated lysosomal membranes on cooling; it starts at approx. 15 degrees C and probably is not complete at 0 degrees C. 3. Incubation of the lysosomes causes an increased potential for loss of latency of the lysosomal enzymes. This potential is not fully expressed at elevated temperature (e.g. 37 degrees C), but is expressed on cooling. 4. The increase at elevated temperature in potential for loss of latency exhibits biphasic kinetics, with an initial rapid phase followed by a slower phase, which is linear with respect to time. The extra loss of latency resulting from the rapid phase in proportional to the temperature of the incubation. 5. Arrhenius plots of the increase is potential for loss of latency during the slow phase for N-acetyl-beta-glucosaminidase and p-nitrophenyl phosphatase exhibit marked deviations from linearity beginning at approx. 15 degrees C. This suggests that the increase in potential for loss of latency is affected by a phase change that occurs around this temperature. 6. Activation energies for the increase in potential for loss of latency at and above 22 degrees C are 53.1+/-5.4kJ/mol (12.7+/-1.3kcal/mol) for N-acetyl-beta-glucosaminidase and 45.2+/-7.5kJ/mol (10.8+/-1.8kcal/mol) for p-nitrophenyl phosphatase. It is postulated that these energies reflect enzymic action, the products of which cause loss of latency to occur on cooling.", "contents": "The temperature-dependence of the loss of latency of lysosomal enzymes. 1. When Triton-filled lysosomes from rat liver are incubated for up to 50min at 37 degrees C, pH7.4, in 0.25m-sucrose, no loss of latency of N-acetyl-beta-glucosaminidase or p-nitrophenyl phosphatase occurs unless the incubated lysosomes are cooled to approx. 15 degrees C. 2. It is suggested that a phase change takes place in the incubated lysosomal membranes on cooling; it starts at approx. 15 degrees C and probably is not complete at 0 degrees C. 3. Incubation of the lysosomes causes an increased potential for loss of latency of the lysosomal enzymes. This potential is not fully expressed at elevated temperature (e.g. 37 degrees C), but is expressed on cooling. 4. The increase at elevated temperature in potential for loss of latency exhibits biphasic kinetics, with an initial rapid phase followed by a slower phase, which is linear with respect to time. The extra loss of latency resulting from the rapid phase in proportional to the temperature of the incubation. 5. Arrhenius plots of the increase is potential for loss of latency during the slow phase for N-acetyl-beta-glucosaminidase and p-nitrophenyl phosphatase exhibit marked deviations from linearity beginning at approx. 15 degrees C. This suggests that the increase in potential for loss of latency is affected by a phase change that occurs around this temperature. 6. Activation energies for the increase in potential for loss of latency at and above 22 degrees C are 53.1+/-5.4kJ/mol (12.7+/-1.3kcal/mol) for N-acetyl-beta-glucosaminidase and 45.2+/-7.5kJ/mol (10.8+/-1.8kcal/mol) for p-nitrophenyl phosphatase. It is postulated that these energies reflect enzymic action, the products of which cause loss of latency to occur on cooling."}
{"id": "PMID:207265", "title": "Complete loss of heparin-releasable triacylglycerol lipase activity after collagenase treatment of the rat liver.", "content": "Lipolytic activity at pH 8.5-9.5 was lowered by approx. 80% in homogenates from livers perfused with collagenase or heparin. No heparin-releasable lipase activity was detected in hepatocytes isolated by collagenase treatment. It is concluded that crude collagenase completely inactivates the plasma-membrane-bound heparin-releasable lipase.", "contents": "Complete loss of heparin-releasable triacylglycerol lipase activity after collagenase treatment of the rat liver. Lipolytic activity at pH 8.5-9.5 was lowered by approx. 80% in homogenates from livers perfused with collagenase or heparin. No heparin-releasable lipase activity was detected in hepatocytes isolated by collagenase treatment. It is concluded that crude collagenase completely inactivates the plasma-membrane-bound heparin-releasable lipase."}
{"id": "PMID:207266", "title": "Effect of parathyrin on the transport properties of isolated renal brush-border vesicles.", "content": "The transport properties of brush-border membrane vesicles isolated by a calcium-precipitation method from the renal cortex of normal and parathyrin (parathyroid hormone)-treated rats were studied by a rapid-filtration technique. Parathyrin elicited a dose-dependent decrease in the Na+-dependent phosphate uptake by the brush-border membrane vesicles, but the uptake of D-glucose, Na+ and mannitol was not affected. A maximum inhibition of 30% was observed after the application of 30 U.S.P. units intramuscularly 1 h before the animals were killed. Intravenous infusion of dibutyryl cyclic AMP (0.5-1.5 MG) also decreased the phosphate uptake by the brush-border vesicles. Both dibutyryl cyclic AMP and parathyrin were ineffective when added in vitro to brush-border membrane vesicles isolated from normal rats. These data suggest that parathyrin exerts its action on the phosphate reabsorption in the renal proximal tubule by affecting the Na+/phosphate co-transport system in the brush-border membrane. The effects of parathyrin on Na+ and glucose transport, however, seem to be due to alterations to the driving forces for transport and not to the brush-border transport systems.", "contents": "Effect of parathyrin on the transport properties of isolated renal brush-border vesicles. The transport properties of brush-border membrane vesicles isolated by a calcium-precipitation method from the renal cortex of normal and parathyrin (parathyroid hormone)-treated rats were studied by a rapid-filtration technique. Parathyrin elicited a dose-dependent decrease in the Na+-dependent phosphate uptake by the brush-border membrane vesicles, but the uptake of D-glucose, Na+ and mannitol was not affected. A maximum inhibition of 30% was observed after the application of 30 U.S.P. units intramuscularly 1 h before the animals were killed. Intravenous infusion of dibutyryl cyclic AMP (0.5-1.5 MG) also decreased the phosphate uptake by the brush-border vesicles. Both dibutyryl cyclic AMP and parathyrin were ineffective when added in vitro to brush-border membrane vesicles isolated from normal rats. These data suggest that parathyrin exerts its action on the phosphate reabsorption in the renal proximal tubule by affecting the Na+/phosphate co-transport system in the brush-border membrane. The effects of parathyrin on Na+ and glucose transport, however, seem to be due to alterations to the driving forces for transport and not to the brush-border transport systems."}
{"id": "PMID:207287", "title": "Analysis of DNA structure by hydroxyapatite columns and ethidium bromide fluorescence techniques. A comparative study and effect on DNA binding.", "content": "Seven duplex DNA preparations have been structurally analyzed by hydroxyapatite column chromatography and an ethidium bromide fluorescence technique. Significant contamination of one preparation with single-stranded DNA was detected by hydroxyapatite column chromatography. Five of the other six preparations were found to contain significant single-stranded regions by the ethidium bromide fluorescence technique. Synthetic poly dAT was found to be duplex in structure. The presence of single-stranded regions considerably influenced DNA binding results in a radioimmunoassay.", "contents": "Analysis of DNA structure by hydroxyapatite columns and ethidium bromide fluorescence techniques. A comparative study and effect on DNA binding. Seven duplex DNA preparations have been structurally analyzed by hydroxyapatite column chromatography and an ethidium bromide fluorescence technique. Significant contamination of one preparation with single-stranded DNA was detected by hydroxyapatite column chromatography. Five of the other six preparations were found to contain significant single-stranded regions by the ethidium bromide fluorescence technique. Synthetic poly dAT was found to be duplex in structure. The presence of single-stranded regions considerably influenced DNA binding results in a radioimmunoassay."}
{"id": "PMID:207288", "title": "[Antiviral activity of plant components. 1st communication: Flavonoids (author's transl)].", "content": "Some drugs effective against influenza contain flavonoids. We therefore examined the antiviral effect of hesperidin, hesperidinmethylchalcon, trihydroxyethylrutin, catechol, quercitrin, rutin and aurantiin against vesicular stromatitis virus (VSV) action on mouse fibroblasts and that of hesperidin against influenza virus in HeLa cells system by means of dye uptake measurements (Finter) and by plaque reduction test, respectively. Preincubation of the cells with the flavonoids 6--8 h before virus addition was inevitable. Protection of cells against virus action persisted for about 24 h and it abruptly disappeared after an addition of hyaluronidase. Maximal inhibition of virus action was achieved with a concentration of 200 microgram/ml flavonoid.", "contents": "[Antiviral activity of plant components. 1st communication: Flavonoids (author's transl)]. Some drugs effective against influenza contain flavonoids. We therefore examined the antiviral effect of hesperidin, hesperidinmethylchalcon, trihydroxyethylrutin, catechol, quercitrin, rutin and aurantiin against vesicular stromatitis virus (VSV) action on mouse fibroblasts and that of hesperidin against influenza virus in HeLa cells system by means of dye uptake measurements (Finter) and by plaque reduction test, respectively. Preincubation of the cells with the flavonoids 6--8 h before virus addition was inevitable. Protection of cells against virus action persisted for about 24 h and it abruptly disappeared after an addition of hyaluronidase. Maximal inhibition of virus action was achieved with a concentration of 200 microgram/ml flavonoid."}
{"id": "PMID:207291", "title": "[Studies of the possible importance of complement in increasing the hemagglutination-inhibiting activity of rabbit IgM against Sendai virus].", "content": "An investigation has been carried out in order to ascertain the effect of the presence of complement on the HI antibodies of the IgM class obtained in rabbit against Sendai virus. Contrary to the results obtained by some AA. with other viruses, in this case the presence of complement in the form of fresh guinea-pig serum has not modified the HI titre. It has however been demonstrated that in the guinea-pig serum an inhibitor is present, which is active towards Sendai virus and can be identified as a 19S alpha-globulin.", "contents": "[Studies of the possible importance of complement in increasing the hemagglutination-inhibiting activity of rabbit IgM against Sendai virus]. An investigation has been carried out in order to ascertain the effect of the presence of complement on the HI antibodies of the IgM class obtained in rabbit against Sendai virus. Contrary to the results obtained by some AA. with other viruses, in this case the presence of complement in the form of fresh guinea-pig serum has not modified the HI titre. It has however been demonstrated that in the guinea-pig serum an inhibitor is present, which is active towards Sendai virus and can be identified as a 19S alpha-globulin."}
{"id": "PMID:207292", "title": "Technetium-99m stannous pyrophosphate scintigraphy in patients with calcification within the cardiac silhouette.", "content": "Technetium-99m stannous pyrophosphate scintiscanning was performed in 22 patients with radiographically detected calcification within the cardiac silhouette. All but one of these scintigrams showed a localised area of increased activity similar to that ordinarily seen in acute myocardial infarction. Scintiscans in 3 patients after removal of the calcified aortic valve reverted to negative. It was concluded that this technique for acute infarct detection may yield false positive results in the presence of cardiac calcification.", "contents": "Technetium-99m stannous pyrophosphate scintigraphy in patients with calcification within the cardiac silhouette. Technetium-99m stannous pyrophosphate scintiscanning was performed in 22 patients with radiographically detected calcification within the cardiac silhouette. All but one of these scintigrams showed a localised area of increased activity similar to that ordinarily seen in acute myocardial infarction. Scintiscans in 3 patients after removal of the calcified aortic valve reverted to negative. It was concluded that this technique for acute infarct detection may yield false positive results in the presence of cardiac calcification."}
{"id": "PMID:207293", "title": "Desensitization of the beta-adrenoceptor of lymphocytes from normal subjects and patients with phaeochromocytoma: studies in vivo.", "content": "1 Following the observation that lymphocyte beta-adrenoceptor responsiveness was not depressed in asthmatics treated only with non-adrenergic drugs we have explored the effects of prolonged exposure to beta-adrenoceptor agonists in normal subjects. 2 Treatment with oral salbutamol (12-16 mg/kg/day for 10 days), or with inhaled salbutamol (3000 microgram/day for 8-10 days) resulted in a significant reduction in lymphocyte beta-adrenoceptor responsiveness. 3 A 48 h infusion of isoxsuprine (10 mg/h) resulted in a marked depression of lymphocyte beta-adrenoceptor responsiveness (P less than 0.001). 4 Prolonged elevation of endogenous catecholamines caused by phaeochromocytoma was also associated with a marked depression of lymphocyte beta-adrenoceptor responsiveness (P less than 0.001). 5 There was no evidence that an increase in phosphodiesterase activity could explain the reduced cyclic AMP response. 6 It is concluded that diminished beta-adrenoceptor response occurs as a response to prolonged exposure to beta-adrenoceptor agonists. It is likely that the diminished response seen in asthmatic subjects can be explained on a similar basis and does not indicate an inherent cellular defect. 7 The possible clinical significance of such changes in asthmatics are discussed.", "contents": "Desensitization of the beta-adrenoceptor of lymphocytes from normal subjects and patients with phaeochromocytoma: studies in vivo. 1 Following the observation that lymphocyte beta-adrenoceptor responsiveness was not depressed in asthmatics treated only with non-adrenergic drugs we have explored the effects of prolonged exposure to beta-adrenoceptor agonists in normal subjects. 2 Treatment with oral salbutamol (12-16 mg/kg/day for 10 days), or with inhaled salbutamol (3000 microgram/day for 8-10 days) resulted in a significant reduction in lymphocyte beta-adrenoceptor responsiveness. 3 A 48 h infusion of isoxsuprine (10 mg/h) resulted in a marked depression of lymphocyte beta-adrenoceptor responsiveness (P less than 0.001). 4 Prolonged elevation of endogenous catecholamines caused by phaeochromocytoma was also associated with a marked depression of lymphocyte beta-adrenoceptor responsiveness (P less than 0.001). 5 There was no evidence that an increase in phosphodiesterase activity could explain the reduced cyclic AMP response. 6 It is concluded that diminished beta-adrenoceptor response occurs as a response to prolonged exposure to beta-adrenoceptor agonists. It is likely that the diminished response seen in asthmatic subjects can be explained on a similar basis and does not indicate an inherent cellular defect. 7 The possible clinical significance of such changes in asthmatics are discussed."}
{"id": "PMID:207294", "title": "Desensitization of the beta-adrenoceptor of lymphocytes from normal subjects and asthmatic patients in vitro.", "content": "1 A lymphocyte culture method has been developed for studying in vitro the effect of prolonged exposure (24 h) to isoprenaline (10(-8) to 10(-6) mol/l) and prostaglandin E1 (PGE1; 2.8 x 10(-6) mol/l). 2 The cyclic AMP response to isoprenaline is reduced by prolonged exposure to isoprenaline. The degree of desensitization is in proportion to the concentration of isoprenaline in the culture medium. 3 Culture with isoprenaline does not reduce the cyclic AMP response to PGE1. 4 Culture for 24 h with PGE1 (2.8 x 10(-6) mol/l) reduces the cyclic AMP response to PGE1. It also significantly reduces the response to isoprenaline. 5 Lymphocytes from asthmatic patients show a similar degree of desensitization to isoprenaline (after 24 h culture with isoprenaline) to that seen in lymphocytes from normal subjects. 6 A modified assay for phosphodiesterase (PDE) activity was developed. PDE activity increased 24.5% (P less than 0.02) after culture with PGE1 but was not significantly affected by culture with isoprenaline. 7 It is concluded that desensitization caused by prolonged exposure to various stimulators of adenylate cyclase is an event dependent on several components, not all of which are yet defined.", "contents": "Desensitization of the beta-adrenoceptor of lymphocytes from normal subjects and asthmatic patients in vitro. 1 A lymphocyte culture method has been developed for studying in vitro the effect of prolonged exposure (24 h) to isoprenaline (10(-8) to 10(-6) mol/l) and prostaglandin E1 (PGE1; 2.8 x 10(-6) mol/l). 2 The cyclic AMP response to isoprenaline is reduced by prolonged exposure to isoprenaline. The degree of desensitization is in proportion to the concentration of isoprenaline in the culture medium. 3 Culture with isoprenaline does not reduce the cyclic AMP response to PGE1. 4 Culture for 24 h with PGE1 (2.8 x 10(-6) mol/l) reduces the cyclic AMP response to PGE1. It also significantly reduces the response to isoprenaline. 5 Lymphocytes from asthmatic patients show a similar degree of desensitization to isoprenaline (after 24 h culture with isoprenaline) to that seen in lymphocytes from normal subjects. 6 A modified assay for phosphodiesterase (PDE) activity was developed. PDE activity increased 24.5% (P less than 0.02) after culture with PGE1 but was not significantly affected by culture with isoprenaline. 7 It is concluded that desensitization caused by prolonged exposure to various stimulators of adenylate cyclase is an event dependent on several components, not all of which are yet defined."}
{"id": "PMID:207295", "title": "Characterization of beta-adrenoceptor subtype mediating the metabolic actions of salbutamol.", "content": "1. The following four intravenous treatments were administered in a balanced, randomized, Latin square design to four healthy volunteers: (1) saline injection (10 min); salbutamol infusion (0.15 microgram kg-1 min-1 for 60 min) (sS), (2) propranolol injection (0.3 mg kg-1 for 10 min); salbutamol infusion (pS), (3) practolol injection (2 mg kg-1 for 10 min); salbutamol infusion (PS) and (4) saline injection; saline infusion (ss).  2. Heart rate was recorded and venous blood taken for estimation of insulin, glucose and potassium before and after each injection (0 and 12-15 min) and at various times during the infusion (30,45,60 and 75 min).  3. The mean, peak % heart rate changes from baseline, control were +65.8%, +23.0%, -10.9% and -12.1%, the mean, peak % glucose changes, +61.0%, +7.1%, +3.6% and +6.9%, and the mean, peak % insulin changes, +298%, +28%, -28% and -43% during the infusions for sS, PS, ss and pS respectively.  4. The mean serum potassium levels before the injections and at the completion of the infusions were 3.98 and 3.08 4.03 and 3.63, 4.07 and 4.15, and 4.03 and 4.13 meq/l for sS, PS, ss and pS respectively.  5. Propanolol completely abolished the cardiac and metabolic responses of salbutamol.  6. Practolol produced only partial cardiac beta-adrenoceptor blockade, but completely inhibited the metabolic actions of salbutamol.", "contents": "Characterization of beta-adrenoceptor subtype mediating the metabolic actions of salbutamol. 1. The following four intravenous treatments were administered in a balanced, randomized, Latin square design to four healthy volunteers: (1) saline injection (10 min); salbutamol infusion (0.15 microgram kg-1 min-1 for 60 min) (sS), (2) propranolol injection (0.3 mg kg-1 for 10 min); salbutamol infusion (pS), (3) practolol injection (2 mg kg-1 for 10 min); salbutamol infusion (PS) and (4) saline injection; saline infusion (ss).  2. Heart rate was recorded and venous blood taken for estimation of insulin, glucose and potassium before and after each injection (0 and 12-15 min) and at various times during the infusion (30,45,60 and 75 min).  3. The mean, peak % heart rate changes from baseline, control were +65.8%, +23.0%, -10.9% and -12.1%, the mean, peak % glucose changes, +61.0%, +7.1%, +3.6% and +6.9%, and the mean, peak % insulin changes, +298%, +28%, -28% and -43% during the infusions for sS, PS, ss and pS respectively.  4. The mean serum potassium levels before the injections and at the completion of the infusions were 3.98 and 3.08 4.03 and 3.63, 4.07 and 4.15, and 4.03 and 4.13 meq/l for sS, PS, ss and pS respectively.  5. Propanolol completely abolished the cardiac and metabolic responses of salbutamol.  6. Practolol produced only partial cardiac beta-adrenoceptor blockade, but completely inhibited the metabolic actions of salbutamol."}
{"id": "PMID:207296", "title": "Adenosine deaminase and adenosine kinase in rat hepatomas and kidney tumours.", "content": "Adenosine deaminase and adenosine kinase have been measured in rat liver, 12 transplantable hepatomas, regenerating, foetal and neonatal liver, adult and neonatal rat kidney and 2 transplantable kidney tumours. Adenosine, deaminase activity, relative to the normal liver value, was elevated 2-4 fold in hepatomas of rapid growth rate, was in the normal range in more slowly growing hepatomas and in regernerating liver, and was low in foetal and neonatal liver. Adenosine kinase activity was decreased, relative to rat liver values, in all the hepatomas; activity of this enzyme gave a negative correlation with tumour growth rate. Kinetic properties of the two enzymes were examined in partially purified preparations. Adenosine deaminases from both liver and rapidly growing hepatoma 3924A were subject to weak product inhibition by inosine. Adenosine kinase from liver and hepatoma 3924A was inhibited by the reaction products ADP and AMP, and the enzyme was also subject to excess substrate inhibition by concentrations of ATP in excess of 1 mM. In rat hepatoma cell lines growing in culture, the toxicity of adenosine correlated inversely with the ratio of adenosine deaminase activity to adenosine kinase activity. Chromatographic measurements showed that hepatoma cells incorporated less extracellular adenosine into their adenine nucleotide pools than did isolated liver cells. These results indicate that increased adenosine deaminase activity and decreased adenosine kinase activity may confer a selective advantage upon the cancer cell.", "contents": "Adenosine deaminase and adenosine kinase in rat hepatomas and kidney tumours. Adenosine deaminase and adenosine kinase have been measured in rat liver, 12 transplantable hepatomas, regenerating, foetal and neonatal liver, adult and neonatal rat kidney and 2 transplantable kidney tumours. Adenosine, deaminase activity, relative to the normal liver value, was elevated 2-4 fold in hepatomas of rapid growth rate, was in the normal range in more slowly growing hepatomas and in regernerating liver, and was low in foetal and neonatal liver. Adenosine kinase activity was decreased, relative to rat liver values, in all the hepatomas; activity of this enzyme gave a negative correlation with tumour growth rate. Kinetic properties of the two enzymes were examined in partially purified preparations. Adenosine deaminases from both liver and rapidly growing hepatoma 3924A were subject to weak product inhibition by inosine. Adenosine kinase from liver and hepatoma 3924A was inhibited by the reaction products ADP and AMP, and the enzyme was also subject to excess substrate inhibition by concentrations of ATP in excess of 1 mM. In rat hepatoma cell lines growing in culture, the toxicity of adenosine correlated inversely with the ratio of adenosine deaminase activity to adenosine kinase activity. Chromatographic measurements showed that hepatoma cells incorporated less extracellular adenosine into their adenine nucleotide pools than did isolated liver cells. These results indicate that increased adenosine deaminase activity and decreased adenosine kinase activity may confer a selective advantage upon the cancer cell."}
{"id": "PMID:207297", "title": "Preparation and characterization of an antiserum to cultured human oat-cell carcinoma cells.", "content": "Viable cultured oat-cell carcinoma cells were used to immunize a goat. The resulting antiserum contained high titres of anti-normal activity and antibodies to CEA. It was also shown, by indirect immunofluorescence, using fluorescein-conjugated rabbit anti-goat Ig, to localize at high titres on the surface membranes of human lung cancer cells of 4 different histological types. Booster immunizations produced a maximum secondary response one week after 2 weekly injections. The course of each immunization has been monitored for activity against normal human tissues, and the final sera have been absorbed with human spleen cells to remove anti-normal activity. Cross-reactivity with the lung-cancer-cell panel and antibodies to CEA persisted in high titre after absorption of anti-normal antibodies, and were present in the ammonium-sulphate-precipitated globulin fraction. The cells used for immunization did not produce detectable amounts of CEA in culture, and were not known to contain CEA prior to this experiment. Removal of anti-CEA antibodies by absorption with purified CEA has not reduced the cross-reactivity of the absorbed antiserum with the panel of human lung-cancer cells.", "contents": "Preparation and characterization of an antiserum to cultured human oat-cell carcinoma cells. Viable cultured oat-cell carcinoma cells were used to immunize a goat. The resulting antiserum contained high titres of anti-normal activity and antibodies to CEA. It was also shown, by indirect immunofluorescence, using fluorescein-conjugated rabbit anti-goat Ig, to localize at high titres on the surface membranes of human lung cancer cells of 4 different histological types. Booster immunizations produced a maximum secondary response one week after 2 weekly injections. The course of each immunization has been monitored for activity against normal human tissues, and the final sera have been absorbed with human spleen cells to remove anti-normal activity. Cross-reactivity with the lung-cancer-cell panel and antibodies to CEA persisted in high titre after absorption of anti-normal antibodies, and were present in the ammonium-sulphate-precipitated globulin fraction. The cells used for immunization did not produce detectable amounts of CEA in culture, and were not known to contain CEA prior to this experiment. Removal of anti-CEA antibodies by absorption with purified CEA has not reduced the cross-reactivity of the absorbed antiserum with the panel of human lung-cancer cells."}
{"id": "PMID:207298", "title": "Solid tumour models for the assessment of different treatment modalities: VII: single vs fractionated doses of 5-fluorouracil on two solid tumours and their hosts.", "content": "The effects of one large single dose of 5-fluorouracil (FU) have been compared to the same amount given in divided doses daily over a 3- or 5-day period. Comparison of the effects of single vs fractionated dosage was made on 2 types of experimental solid tumour with different growth, cell kinetic, histological and metastasizing properties. The tumour response was essentially the same for both the single and fractionated dose schedules.There were marked increases in animal mortality from drug toxicity following fractionated doses of FU compared to one large single dose. Mortality in animals with Tumour 3924A increased from 10% following one large single dose to 60% for animals given daily fractionated doses for 3 days, and 80% for animals given daily fractionated doses for 5 days. Total marrow reserve was measured by the total DNA content of tibial marrow. The nadir of 6 days for loss of total tibial marrow DNA following one large dose of FU was increased to 9 days for both fractionated schedules of FU. The 3-day delay in recovery of the marrow prevented recovery within the time frame necessary for animal survival. The inference from these experimental cancer-treatment studies is that daily fractions of chemotherapeutic agents such as FU result in increased morbidity and mortality, without benefit in the control of the solid tumour. The results question the advisability of the clinical practice of initially giving small daily \"loading doses\" of proliferation-dependent agents such as FU.These results emphasize the need for more precise information on the temporal relationship between the response and recovery of the host and the response and recovery of the solid tumour. They also emphasize the need for a better clinical understanding of the time sequence of solid-tumour recovery in relation to the time sequence of marrow recovery.", "contents": "Solid tumour models for the assessment of different treatment modalities: VII: single vs fractionated doses of 5-fluorouracil on two solid tumours and their hosts. The effects of one large single dose of 5-fluorouracil (FU) have been compared to the same amount given in divided doses daily over a 3- or 5-day period. Comparison of the effects of single vs fractionated dosage was made on 2 types of experimental solid tumour with different growth, cell kinetic, histological and metastasizing properties. The tumour response was essentially the same for both the single and fractionated dose schedules.There were marked increases in animal mortality from drug toxicity following fractionated doses of FU compared to one large single dose. Mortality in animals with Tumour 3924A increased from 10% following one large single dose to 60% for animals given daily fractionated doses for 3 days, and 80% for animals given daily fractionated doses for 5 days. Total marrow reserve was measured by the total DNA content of tibial marrow. The nadir of 6 days for loss of total tibial marrow DNA following one large dose of FU was increased to 9 days for both fractionated schedules of FU. The 3-day delay in recovery of the marrow prevented recovery within the time frame necessary for animal survival. The inference from these experimental cancer-treatment studies is that daily fractions of chemotherapeutic agents such as FU result in increased morbidity and mortality, without benefit in the control of the solid tumour. The results question the advisability of the clinical practice of initially giving small daily \"loading doses\" of proliferation-dependent agents such as FU.These results emphasize the need for more precise information on the temporal relationship between the response and recovery of the host and the response and recovery of the solid tumour. They also emphasize the need for a better clinical understanding of the time sequence of solid-tumour recovery in relation to the time sequence of marrow recovery."}
{"id": "PMID:207299", "title": "A fine structural study of the removal of the effectiveness of benzo-pyrone treatment of lymphoedema by the destruction of the macrophages by silica.", "content": "Macroscopical, light microscopical and electronmicroscopical observations were made of the diaphragm, skin and brain of rats, some of which were treated with intraperitoneal silica for 8 days (after being given it i.v. for 2 days). The diaphragms showed a most remarkable increase in fibroblast activity and fibrosis beneath the peritoneal mesothelium (which was disintegrating). Deep to this there were many disintegrating macrophages, and much oedema and increased protein concentration. Ligation of the cervical lymphatics produced the usual changes of lymphoedema in the skin and brain. This was greatly reduced in the animals treated with a mixture of benzo-pyrones. However, in those animals also treated with silica, the benzo-pyrones had no effect on the amount of oedema or of protein. In all the animals except those treated with silica, lymphoedema was accompanied by considerable numbers of macrophages entering the affected tissues; in those treated with silica, these numbers were greatly reduced.", "contents": "A fine structural study of the removal of the effectiveness of benzo-pyrone treatment of lymphoedema by the destruction of the macrophages by silica. Macroscopical, light microscopical and electronmicroscopical observations were made of the diaphragm, skin and brain of rats, some of which were treated with intraperitoneal silica for 8 days (after being given it i.v. for 2 days). The diaphragms showed a most remarkable increase in fibroblast activity and fibrosis beneath the peritoneal mesothelium (which was disintegrating). Deep to this there were many disintegrating macrophages, and much oedema and increased protein concentration. Ligation of the cervical lymphatics produced the usual changes of lymphoedema in the skin and brain. This was greatly reduced in the animals treated with a mixture of benzo-pyrones. However, in those animals also treated with silica, the benzo-pyrones had no effect on the amount of oedema or of protein. In all the animals except those treated with silica, lymphoedema was accompanied by considerable numbers of macrophages entering the affected tissues; in those treated with silica, these numbers were greatly reduced."}
{"id": "PMID:207302", "title": "DNA unwinding protein from meiotic cells of Lilium.", "content": "An ATP-dependent DNA unwinding protein is present at a high level of activity in meiotic cells of lilies. The protein also acts as a DNA-dependent ATPase, the single strand form being the preferred cofactor. It binds in the absence of ATP to single-strand DNA and to ends or nicks in duplex DNA. A 3'-OH terminus is required for binding at duplex ends; such binding is highly stable. Unwinding occurs in the presence of ATP, and it is limited to about 50 base pairs per end or 400-500 base pairs per nick. The ATP hydrolyzed during unwinding is distinguishable from ATP hydrolysis in the presence of single-strand DNA.", "contents": "DNA unwinding protein from meiotic cells of Lilium. An ATP-dependent DNA unwinding protein is present at a high level of activity in meiotic cells of lilies. The protein also acts as a DNA-dependent ATPase, the single strand form being the preferred cofactor. It binds in the absence of ATP to single-strand DNA and to ends or nicks in duplex DNA. A 3'-OH terminus is required for binding at duplex ends; such binding is highly stable. Unwinding occurs in the presence of ATP, and it is limited to about 50 base pairs per end or 400-500 base pairs per nick. The ATP hydrolyzed during unwinding is distinguishable from ATP hydrolysis in the presence of single-strand DNA."}
{"id": "PMID:207304", "title": "Chemical and enzymatic properties of riboflavin analogues.", "content": "The chemical and enzymatic properties of 26 analogues of riboflavin are presented. These analogues include both endo- and exocyclically substituted isoalloxazines with redox potentials from -370 to -128 mV. Physical and chemical data such as the electronic absorption spectra, pKas, and redox potentials of the analogues are presented and are discussed with respect to preferred tautomeric and resonance forms. Like riboflavin, most of the analogues are shown to be catalytic oxidants of dihydro-5-deazaflavins. Analogue binding to egg white binding apoprotein has been quantitated and serves to determine the origins of binding site specificity for this protein. Nearly all of the analogues that possess D-ribityl groups are found to be processed to the FAD level by the flavokinase/FAD synthetase system of Brevibacterium ammoniagenes. Most extensively studied are the reactivities of the analogues with the NAD(P)H:flavin oxidoreductase of Beneckea harveyi. Many of the analogues are substrates in this enzymatic redox reaction, and a linear free energy-rate relation (log Vmax vs. E0' of the analogue) is seen that parallels similar relationships in the nonenzymatic oxidation of dihydro-5-deazaflavins. This suggests a common mechanism for the reactions of such diverse flavins as riboflavin, 5-deazariboflavin, and 1-deazariboflavin.", "contents": "Chemical and enzymatic properties of riboflavin analogues. The chemical and enzymatic properties of 26 analogues of riboflavin are presented. These analogues include both endo- and exocyclically substituted isoalloxazines with redox potentials from -370 to -128 mV. Physical and chemical data such as the electronic absorption spectra, pKas, and redox potentials of the analogues are presented and are discussed with respect to preferred tautomeric and resonance forms. Like riboflavin, most of the analogues are shown to be catalytic oxidants of dihydro-5-deazaflavins. Analogue binding to egg white binding apoprotein has been quantitated and serves to determine the origins of binding site specificity for this protein. Nearly all of the analogues that possess D-ribityl groups are found to be processed to the FAD level by the flavokinase/FAD synthetase system of Brevibacterium ammoniagenes. Most extensively studied are the reactivities of the analogues with the NAD(P)H:flavin oxidoreductase of Beneckea harveyi. Many of the analogues are substrates in this enzymatic redox reaction, and a linear free energy-rate relation (log Vmax vs. E0' of the analogue) is seen that parallels similar relationships in the nonenzymatic oxidation of dihydro-5-deazaflavins. This suggests a common mechanism for the reactions of such diverse flavins as riboflavin, 5-deazariboflavin, and 1-deazariboflavin."}
{"id": "PMID:207308", "title": "Spin-labeled ribonuclease A. Effects of chemical, enzymatic, and physical modifications on enzyme conformation.", "content": "3-SLHis-105-RNase A is an active derivative of ribonuclease A (RNase A) spin-labeled at the 3 position of the imidazole ring of histidine-105. The spin-labeled enzyme has been modified by urea denaturation, reduction, reduction-carboxymethylation, performic acid oxidation, and digestion with proteolytic enzymes in order to monitor changes in the geometry of the protein by changes in the electron paramagnetic resonance (EPR) spectrum of the nitroxide spin-label probe. The results of these experiments indicate that the spin-label attached to histidine-105 of RNase A is sensitive to modifications affecting the conformational integrity of the molecule and to the reconstituting effects of various active-center ligands.", "contents": "Spin-labeled ribonuclease A. Effects of chemical, enzymatic, and physical modifications on enzyme conformation. 3-SLHis-105-RNase A is an active derivative of ribonuclease A (RNase A) spin-labeled at the 3 position of the imidazole ring of histidine-105. The spin-labeled enzyme has been modified by urea denaturation, reduction, reduction-carboxymethylation, performic acid oxidation, and digestion with proteolytic enzymes in order to monitor changes in the geometry of the protein by changes in the electron paramagnetic resonance (EPR) spectrum of the nitroxide spin-label probe. The results of these experiments indicate that the spin-label attached to histidine-105 of RNase A is sensitive to modifications affecting the conformational integrity of the molecule and to the reconstituting effects of various active-center ligands."}
{"id": "PMID:207310", "title": "Librational motion of an \"immobilized\" spin label: hemoglobin spin labeled by a maleimide derivative.", "content": "The spin label Tempo-maleimide, when \"immobilized\" in hemoglobin, is shown to exhibit motional fluctuation whose amplitude and/or frequency depend on temperature and solution conditions. These motional fluctuations are observable by several electron spin resonance techniques. For desalted hemoglobin the fluctuations are detectable at approximately -15 degrees C using saturation transfer techniques and at approximately +25 degrees C using line-width measurements of normal absorption spectra. In ammonium sulfate precipitated hemoglobin, however, motional fluctuations are not detectable by either technique up to at least 40 degrees C. The most probable mechanism for spin-label motion appears to be either fluctuations in protein conformation which affect the label binding site or conformational transitions of the nitroxide ring itself. These motional fluctuations are shown to introduce a librational character to the overall label motion during hemoglobin rotational diffusion, with the librational motion significantly affecting the use of spin-label spectral shapes to calculate hemoglobin rotational correlation times.", "contents": "Librational motion of an \"immobilized\" spin label: hemoglobin spin labeled by a maleimide derivative. The spin label Tempo-maleimide, when \"immobilized\" in hemoglobin, is shown to exhibit motional fluctuation whose amplitude and/or frequency depend on temperature and solution conditions. These motional fluctuations are observable by several electron spin resonance techniques. For desalted hemoglobin the fluctuations are detectable at approximately -15 degrees C using saturation transfer techniques and at approximately +25 degrees C using line-width measurements of normal absorption spectra. In ammonium sulfate precipitated hemoglobin, however, motional fluctuations are not detectable by either technique up to at least 40 degrees C. The most probable mechanism for spin-label motion appears to be either fluctuations in protein conformation which affect the label binding site or conformational transitions of the nitroxide ring itself. These motional fluctuations are shown to introduce a librational character to the overall label motion during hemoglobin rotational diffusion, with the librational motion significantly affecting the use of spin-label spectral shapes to calculate hemoglobin rotational correlation times."}
{"id": "PMID:207311", "title": "Circular dichroism and circular polarization of luminescence of reduced nicotinamide adenine dinucleotide in solution and bound to dehydrogenases.", "content": "The CD (circular dichroism) and CPL (circular polarization of luminescence) spectra of NADPH in aqueous solution were studied and found to be markedly different. The spectra were not affected by cleavage of the coenzyme molecule with phosphodiesterase. The differences are thus not due to the existence of extended and folded conformations of NADPH and it is concluded that they originate in excited state conformational changes of the nicotinamide--ribose fragment. Opposite signs of both the CD and CPL spectra were observed for NADH bound to horse liver alcohol dehydrogenase and to beef heart lactate dehydrogenase indicating structural differences between the nicotinamide binding sites. The binding of substrate analogues to enzyme--coenzyme complexes did not affect the CD spectra and hence no significant conformational changes are induced upon formation of the ternary complexes. No changes in the CPL spectrum of NADH bound to lactate dehydrogenase were observed upon adding oxalate to form the ternary complex. Marked differences were found between the CPL spectra of binary and ternary complexes with liver alcohol dehydrogenase, while the CD spectra of these complexes were identical. It is concluded that a conformational change of the excited NADH molecule occurs in the binary but not in the ternary complex involving LADH, thus indicating an increased  rigidity of the latter complex.", "contents": "Circular dichroism and circular polarization of luminescence of reduced nicotinamide adenine dinucleotide in solution and bound to dehydrogenases. The CD (circular dichroism) and CPL (circular polarization of luminescence) spectra of NADPH in aqueous solution were studied and found to be markedly different. The spectra were not affected by cleavage of the coenzyme molecule with phosphodiesterase. The differences are thus not due to the existence of extended and folded conformations of NADPH and it is concluded that they originate in excited state conformational changes of the nicotinamide--ribose fragment. Opposite signs of both the CD and CPL spectra were observed for NADH bound to horse liver alcohol dehydrogenase and to beef heart lactate dehydrogenase indicating structural differences between the nicotinamide binding sites. The binding of substrate analogues to enzyme--coenzyme complexes did not affect the CD spectra and hence no significant conformational changes are induced upon formation of the ternary complexes. No changes in the CPL spectrum of NADH bound to lactate dehydrogenase were observed upon adding oxalate to form the ternary complex. Marked differences were found between the CPL spectra of binary and ternary complexes with liver alcohol dehydrogenase, while the CD spectra of these complexes were identical. It is concluded that a conformational change of the excited NADH molecule occurs in the binary but not in the ternary complex involving LADH, thus indicating an increased  rigidity of the latter complex."}
{"id": "PMID:207314", "title": "Mechanistic study of the addition of pyruvate to NAD+ catalyzed by lactate dehydrogenase.", "content": "The binary complex of NAD+ and dogfish A4 lactate dehydrogenase reacts reversibly with pyruvate enol to produce an inactive, enzyme-adduct complex, in which the nicotinamide and pyruvate moieties are linked by means of a covalent bond. This process is examined in both the forward and reverse directions as a function of reactant and buffer concentrations at pH 7, under conditions where the enolization of pyruvate is at equilibrium, and the involvement of complexes with stoichiometry E.NAD, E.NAD.PyrE, and E.NAD.PyrK is defined. (The subscripts, E and K, indicate the enol and keto forms of pyruvate.) One pathway for formation of the adduct complex involves the prior formation of the E.NAD.PyrE complex from E.NAD and pyruvate enol; the alternative pathway involves formation of the same complex via the enolization of E.NAD.PyrK, a process that is catalyzed by an external (nonenzymic) base. The possible use of the adduct reaction as a model for the normal enzymic reaction is considered.", "contents": "Mechanistic study of the addition of pyruvate to NAD+ catalyzed by lactate dehydrogenase. The binary complex of NAD+ and dogfish A4 lactate dehydrogenase reacts reversibly with pyruvate enol to produce an inactive, enzyme-adduct complex, in which the nicotinamide and pyruvate moieties are linked by means of a covalent bond. This process is examined in both the forward and reverse directions as a function of reactant and buffer concentrations at pH 7, under conditions where the enolization of pyruvate is at equilibrium, and the involvement of complexes with stoichiometry E.NAD, E.NAD.PyrE, and E.NAD.PyrK is defined. (The subscripts, E and K, indicate the enol and keto forms of pyruvate.) One pathway for formation of the adduct complex involves the prior formation of the E.NAD.PyrE complex from E.NAD and pyruvate enol; the alternative pathway involves formation of the same complex via the enolization of E.NAD.PyrK, a process that is catalyzed by an external (nonenzymic) base. The possible use of the adduct reaction as a model for the normal enzymic reaction is considered."}
{"id": "PMID:207315", "title": "Isotope-tapping experiments with rabbit liver fructose bisphosphatase.", "content": "Isotope-trapping experiments with mental-free rabbit liver fructose 1,6-bisphosphatase have shown that enzyme-bound D-fructose 1,6-bisphosphate completely dissociates prior to enzyme turnover initiated by Mn2+ as the catalytic metal. The exchange rate of the binary enzyme-D-fructose 1,6-bisphosphate complex with the substrate pool is, therefore, more rapid than its conversion to products, suggesting that structural Mn2+ is necessary for productive substarate binding. Rapid-quench isotope-trapping experiments confirm the requirement for structural Mn2+ ions for productive binding to occur. These experiments also show that an ordered formation of the enzyme-Mn2+ s-D-fructose 1,6-bisphosphate ternary complex which features metal-ion addition prior to substrate constitutes a catalytically competent pathway in the mechanism of fructose 1,6-bisphosphatase and that all four subunits are active in a single turnover event.", "contents": "Isotope-tapping experiments with rabbit liver fructose bisphosphatase. Isotope-trapping experiments with mental-free rabbit liver fructose 1,6-bisphosphatase have shown that enzyme-bound D-fructose 1,6-bisphosphate completely dissociates prior to enzyme turnover initiated by Mn2+ as the catalytic metal. The exchange rate of the binary enzyme-D-fructose 1,6-bisphosphate complex with the substrate pool is, therefore, more rapid than its conversion to products, suggesting that structural Mn2+ is necessary for productive substarate binding. Rapid-quench isotope-trapping experiments confirm the requirement for structural Mn2+ ions for productive binding to occur. These experiments also show that an ordered formation of the enzyme-Mn2+ s-D-fructose 1,6-bisphosphate ternary complex which features metal-ion addition prior to substrate constitutes a catalytically competent pathway in the mechanism of fructose 1,6-bisphosphatase and that all four subunits are active in a single turnover event."}
{"id": "PMID:207316", "title": "Spin-label and deuterium order parameter discrepancies in bilayers: one possible explanation.", "content": "We have simulated electron spin resonance spectra of anisotropically immobilized spin labels of the type seen in lipid and soap-like bilayers using a rigorous formalism which explicitly includes the effects of spin-label motion. In most bilayer systems, spin-label experiments have shown lower order parameters then deuterium-label experiments. In the past this apparent decrease in the order parameters was thought to reflect the distortion of the bilayer by the doxyl ring of the spin probes. We wish to report that this type of discrepancy may be due to the neglect of important motional effects in the time-independent effective Hamiltonian formalisms used in previous interpretations of anisotropically immobilized spin label spectra. That the true order parameters may be the same can be shown by including slow motional corrections in the effective Hamiltonian formalism. The larger volume of the doxyl ring may change the apparent order parameter by increasing the importance of the slow motional effects, as opposed to causing a real decrease in the order parameter, as previously proposed.", "contents": "Spin-label and deuterium order parameter discrepancies in bilayers: one possible explanation. We have simulated electron spin resonance spectra of anisotropically immobilized spin labels of the type seen in lipid and soap-like bilayers using a rigorous formalism which explicitly includes the effects of spin-label motion. In most bilayer systems, spin-label experiments have shown lower order parameters then deuterium-label experiments. In the past this apparent decrease in the order parameters was thought to reflect the distortion of the bilayer by the doxyl ring of the spin probes. We wish to report that this type of discrepancy may be due to the neglect of important motional effects in the time-independent effective Hamiltonian formalisms used in previous interpretations of anisotropically immobilized spin label spectra. That the true order parameters may be the same can be shown by including slow motional corrections in the effective Hamiltonian formalism. The larger volume of the doxyl ring may change the apparent order parameter by increasing the importance of the slow motional effects, as opposed to causing a real decrease in the order parameter, as previously proposed."}
{"id": "PMID:207317", "title": "Anomalies in the polarographic measurement of cytochrome oxidase activity.", "content": "Reaction kinetics of the reduction of O2 by cytochrome oxidase follow essentially the same rate equation as that proposed for the oxidation of cytochrome c. However, the apparent second order rate constant varies with the oxidase concentration. The redox level of cytochrome c at the steady state was found to be essentially temperature-independent. Currently recognized pathways (or mechanisms) of electron transport from cytochrome c to O2 do not predict, and cannot account for the occurrence of these phenomena.", "contents": "Anomalies in the polarographic measurement of cytochrome oxidase activity. Reaction kinetics of the reduction of O2 by cytochrome oxidase follow essentially the same rate equation as that proposed for the oxidation of cytochrome c. However, the apparent second order rate constant varies with the oxidase concentration. The redox level of cytochrome c at the steady state was found to be essentially temperature-independent. Currently recognized pathways (or mechanisms) of electron transport from cytochrome c to O2 do not predict, and cannot account for the occurrence of these phenomena."}
{"id": "PMID:207318", "title": "Characterization of the iron-sulfur protein of the mitochondrial outer membrane partially purified from beef kidney cortex.", "content": "The iron-sulfur protein present in the mitochondrial outer membrane has been partially purified from beef kidney cortex mitochondria by means of selective solubilization followed by DEAE-cellulose chromatography. The EPR spectrum of the iron-sulfur protein with g-values at 2.01, 1.94 and 1.89 was well resolved up to 200 K which is unusual for an iron-sulfur protein. Analyses confirmed a center with two iron and two labile sulfur atoms in the protein. By measuring the effect of oxidation-reduction potential on the EPR signal amplitude, midpoint potentials at pH 7.2 were determined both for the purified iron-sulfur protein, +75 (+/- 5) mV, and in prepared mitochondrial outer membrane, +62 (+/- 6) mV. At pH 8.2 slightly lower values were indicated, +62 and 52 mV, respectively. The oxidation-reduction equilibrium involved a one electron transfer. A functional relationship to the rotenone-insensitive NADH-cytochrome c oxidoreductase in the mitochondrial outer membrane is suggested. Both this activity and the iron-sulfur center were sensitive to acidities slightly below pH 7 in contrast to the iron-sulfur centers of the inner membrane.", "contents": "Characterization of the iron-sulfur protein of the mitochondrial outer membrane partially purified from beef kidney cortex. The iron-sulfur protein present in the mitochondrial outer membrane has been partially purified from beef kidney cortex mitochondria by means of selective solubilization followed by DEAE-cellulose chromatography. The EPR spectrum of the iron-sulfur protein with g-values at 2.01, 1.94 and 1.89 was well resolved up to 200 K which is unusual for an iron-sulfur protein. Analyses confirmed a center with two iron and two labile sulfur atoms in the protein. By measuring the effect of oxidation-reduction potential on the EPR signal amplitude, midpoint potentials at pH 7.2 were determined both for the purified iron-sulfur protein, +75 (+/- 5) mV, and in prepared mitochondrial outer membrane, +62 (+/- 6) mV. At pH 8.2 slightly lower values were indicated, +62 and 52 mV, respectively. The oxidation-reduction equilibrium involved a one electron transfer. A functional relationship to the rotenone-insensitive NADH-cytochrome c oxidoreductase in the mitochondrial outer membrane is suggested. Both this activity and the iron-sulfur center were sensitive to acidities slightly below pH 7 in contrast to the iron-sulfur centers of the inner membrane."}
{"id": "PMID:207319", "title": "EPR properties of the reaction center of Rhodopseudomas gelatinosa in situ and in a detergent-solubilized form.", "content": "The photochemical reaction centers from a variety of purple photosynthetic bacteria are composed of a trimer of protein subunits. However, the recently isolated reaction center from Rhodopseudomonas gelatinosa appears to have only two subunits. In this paper we examine the EPR characteristics of the primary photochemical reactants in this species, and compare them with those of other species. Despite of the differences in protein composition, no dramatic differences in EPR properties are seen in vivo, although some interesting effects are seen upon solubilization of the reaction center, which may be related to the unusual lability of the isolated preparation. Perhaps the most noteworthy phenomenon seen in Rps. gelatinosa is the apparent ability of electrons on the reduced intermediary electron carrier to tunnel at low temperatures to the oxidized c-type cytochrome, which has not been seen in other species studied to date.", "contents": "EPR properties of the reaction center of Rhodopseudomas gelatinosa in situ and in a detergent-solubilized form. The photochemical reaction centers from a variety of purple photosynthetic bacteria are composed of a trimer of protein subunits. However, the recently isolated reaction center from Rhodopseudomonas gelatinosa appears to have only two subunits. In this paper we examine the EPR characteristics of the primary photochemical reactants in this species, and compare them with those of other species. Despite of the differences in protein composition, no dramatic differences in EPR properties are seen in vivo, although some interesting effects are seen upon solubilization of the reaction center, which may be related to the unusual lability of the isolated preparation. Perhaps the most noteworthy phenomenon seen in Rps. gelatinosa is the apparent ability of electrons on the reduced intermediary electron carrier to tunnel at low temperatures to the oxidized c-type cytochrome, which has not been seen in other species studied to date."}
{"id": "PMID:207320", "title": "Control of respiration in proteoliposomes containing cytochrome aa3. I. Stimulation by valinomycin and uncoupler.", "content": "1. Both valinomycin and p-trifluoromethoxy carbonyl cyanide phenylhydrazone (FCCP) are required for full release of respiration by cytochrome c oxidase-containing proteoliposomes (prepared by sonicating beef heart cytochrome aa3 in salt solution with 4 parts phosphatidylcholine, 4 parts phosphatidylethanolamine and 2 parts cardiolipin) in the presence of external ascorbate and cytochrome c. In the absence of valinomycin the response to FCCP is rather sluggish, as reported by Wrigglesworth et al. (1976) (Abstracts, 10th Int. Congr. Biochem., No. 06-6-230). 2. The Km for cytochrome c in 67 mM, pH 7.4, phosphate buffer with ascorbate as substrate, was 9 micrometer in both absence and presence of valinomycin and FCCP. Energization thus acts non-competitively towards cytochrome c oxidation. 3. The apparent Km for oxygen is greater in the energized than in the deenergized state; double reciprocal plots of respiration rate versus oxygen concentration are concave downward in the absence of uncouplers, as found with intact mitochondria. Energization thus acts \"competitively\" towards oxygen. 4. Despite the lack of a functional ATPase system, all the kinetic features of energization found in intact mitochondria can be mimicked in the reconstituted liposomes. This supports the chemiosmotic idea that electrical and perhaps H+ gradients modify the oxidase activity in reconstituted vesicles.", "contents": "Control of respiration in proteoliposomes containing cytochrome aa3. I. Stimulation by valinomycin and uncoupler. 1. Both valinomycin and p-trifluoromethoxy carbonyl cyanide phenylhydrazone (FCCP) are required for full release of respiration by cytochrome c oxidase-containing proteoliposomes (prepared by sonicating beef heart cytochrome aa3 in salt solution with 4 parts phosphatidylcholine, 4 parts phosphatidylethanolamine and 2 parts cardiolipin) in the presence of external ascorbate and cytochrome c. In the absence of valinomycin the response to FCCP is rather sluggish, as reported by Wrigglesworth et al. (1976) (Abstracts, 10th Int. Congr. Biochem., No. 06-6-230). 2. The Km for cytochrome c in 67 mM, pH 7.4, phosphate buffer with ascorbate as substrate, was 9 micrometer in both absence and presence of valinomycin and FCCP. Energization thus acts non-competitively towards cytochrome c oxidation. 3. The apparent Km for oxygen is greater in the energized than in the deenergized state; double reciprocal plots of respiration rate versus oxygen concentration are concave downward in the absence of uncouplers, as found with intact mitochondria. Energization thus acts \"competitively\" towards oxygen. 4. Despite the lack of a functional ATPase system, all the kinetic features of energization found in intact mitochondria can be mimicked in the reconstituted liposomes. This supports the chemiosmotic idea that electrical and perhaps H+ gradients modify the oxidase activity in reconstituted vesicles."}
{"id": "PMID:207321", "title": "Purification and characterization of cytochrome O from Azotobacter vinelandii.", "content": "The membrane-bound cytochrome O has been solubilized from the Azotobacter vinelandii electron transport particle and further purified by use of conventional chromatographic procedures. The spectral characteristics as well as the other properties noted for purified cytochrome O are reported herein.", "contents": "Purification and characterization of cytochrome O from Azotobacter vinelandii. The membrane-bound cytochrome O has been solubilized from the Azotobacter vinelandii electron transport particle and further purified by use of conventional chromatographic procedures. The spectral characteristics as well as the other properties noted for purified cytochrome O are reported herein."}
{"id": "PMID:207322", "title": "Preparation of membrane vesicles from isolated myelin: studies on functional and structural properties.", "content": "Myelin membranes purified from bovine brain are shown to form membrane vesicles when incubated in hypotonic buffer. Following restoration of isotonicity a resealing of the membrane occurs as judged by a significant decrease in 22Na+ permeability. Electron spin resonance measurements using stearic acid spin label I indicate a small decrease in membrane fluidity with increasing ionic strength between 50 and 80 mM NaCl. Iodination of myelin membrane vesicles by lactoperoxidase shows a four-fold increase in the amount of iodine incorporation into the myeline basic protein from 0--150 mM NaCl, while the iodination of the proteolipid protein remains essentially unaffected by the change in ionic strength. This dependence of the iodination of the myelin basic protein on the ionic strength can be explained by the electrostatic interactions of this protein with membrane lipids. In view of striking analogies with studies on model membranes correlating protein binding with membrane permeability changes, we suggest a similar structure-function relationship for the myelin basic protein.", "contents": "Preparation of membrane vesicles from isolated myelin: studies on functional and structural properties. Myelin membranes purified from bovine brain are shown to form membrane vesicles when incubated in hypotonic buffer. Following restoration of isotonicity a resealing of the membrane occurs as judged by a significant decrease in 22Na+ permeability. Electron spin resonance measurements using stearic acid spin label I indicate a small decrease in membrane fluidity with increasing ionic strength between 50 and 80 mM NaCl. Iodination of myelin membrane vesicles by lactoperoxidase shows a four-fold increase in the amount of iodine incorporation into the myeline basic protein from 0--150 mM NaCl, while the iodination of the proteolipid protein remains essentially unaffected by the change in ionic strength. This dependence of the iodination of the myelin basic protein on the ionic strength can be explained by the electrostatic interactions of this protein with membrane lipids. In view of striking analogies with studies on model membranes correlating protein binding with membrane permeability changes, we suggest a similar structure-function relationship for the myelin basic protein."}
{"id": "PMID:207323", "title": "Binding of polylysine to charged bilayer membranes: molecular organization of a lipid.peptide complex.", "content": "The interaction between a positively charged peptide (poly-L-lysine) and model membranes containing charged lipids has been investigated. Conformational changes of the polypeptide as well as changes in the membrane lipid distribution were observed upon lipid-protein agglutination: 1. The strong binding of polylysine is shown directly by the use of spinlabelled polypeptide. Upon binding to phosphatidic acid a shift in the hyperfine coupling constant from 16.5 to 14.6 Oe is observed. The spectrum of the lipid-bound peptide is superimposed on the spectrum of polylysine in solution. Half of the lysine groups are bound to the charged membranes. A change in the conformation of polylysine from a random coil to a partially ordered configuration is suggested. 2. Spin labelling of the lipid component gives evidence concerning the molecular organization of a lipid mixture containing charged phosphatitid acid. Addition of polylysine induces the formation of crystalline patches of bound phosphatidic acid. 3. Excimer forming pyrene decanoic acid has been employed. Addition of positively charged polylysine (pH 9.0) to phosphatidic acid membranes increases the transition temperature of the lipid from Tt = 50 to Tt = 62 degrees C. Thus, a lipid segregation of lipid into regions of phosphatidic acid bound to the peptide which differ in their microviscosity from the surrounding membrane is induced. One lysine group binds one phosphatidic acid molecule, but only half of the phosphatidic acid is bound. 4. Direct evidence for charge induced domain formation in lipid mixtures containing phosphatidic acid is given by electron microscopy. Addition of polylysine leads to a change in the surface curvature of the bound charged lipid. The domain size is estimated from the electron micrographs. The number of domains present is dependent on both the ratio of charged to uncharged lipids as well as on the amount of polylysine added to the vesicles. The size of the domains is not dependent on membrane composition. However, the size seems to increase in a stepwise manner that is correlated with a multiple of the area covered by one polylysine molecule.", "contents": "Binding of polylysine to charged bilayer membranes: molecular organization of a lipid.peptide complex. The interaction between a positively charged peptide (poly-L-lysine) and model membranes containing charged lipids has been investigated. Conformational changes of the polypeptide as well as changes in the membrane lipid distribution were observed upon lipid-protein agglutination: 1. The strong binding of polylysine is shown directly by the use of spinlabelled polypeptide. Upon binding to phosphatidic acid a shift in the hyperfine coupling constant from 16.5 to 14.6 Oe is observed. The spectrum of the lipid-bound peptide is superimposed on the spectrum of polylysine in solution. Half of the lysine groups are bound to the charged membranes. A change in the conformation of polylysine from a random coil to a partially ordered configuration is suggested. 2. Spin labelling of the lipid component gives evidence concerning the molecular organization of a lipid mixture containing charged phosphatitid acid. Addition of polylysine induces the formation of crystalline patches of bound phosphatidic acid. 3. Excimer forming pyrene decanoic acid has been employed. Addition of positively charged polylysine (pH 9.0) to phosphatidic acid membranes increases the transition temperature of the lipid from Tt = 50 to Tt = 62 degrees C. Thus, a lipid segregation of lipid into regions of phosphatidic acid bound to the peptide which differ in their microviscosity from the surrounding membrane is induced. One lysine group binds one phosphatidic acid molecule, but only half of the phosphatidic acid is bound. 4. Direct evidence for charge induced domain formation in lipid mixtures containing phosphatidic acid is given by electron microscopy. Addition of polylysine leads to a change in the surface curvature of the bound charged lipid. The domain size is estimated from the electron micrographs. The number of domains present is dependent on both the ratio of charged to uncharged lipids as well as on the amount of polylysine added to the vesicles. The size of the domains is not dependent on membrane composition. However, the size seems to increase in a stepwise manner that is correlated with a multiple of the area covered by one polylysine molecule."}
{"id": "PMID:207324", "title": "Protein-bound histidine, as well as protein-bound serine, residues are sites of phosphorylation in the synaptic plasma membrane.", "content": "When synaptic plasma membrane fragments are incubated with ATP in the presence of Mg2+, phosphate is transferred, not only to protein-bound serine, but also to protein-bound histidine. The phosphorylation of protein-bound serine is stimulated by cyclic AMP and has a Km for ATP of about 0.12 mM, both in the presence and absence of cyclic AMP. By contrast, the phosphorylation of protein-bound histidine is unaffected by cyclic AMP and does not follow Michaelis-Menton kinetics since a non-linear double reciprocal plot is given when activity is measured at various ATP concentrations.", "contents": "Protein-bound histidine, as well as protein-bound serine, residues are sites of phosphorylation in the synaptic plasma membrane. When synaptic plasma membrane fragments are incubated with ATP in the presence of Mg2+, phosphate is transferred, not only to protein-bound serine, but also to protein-bound histidine. The phosphorylation of protein-bound serine is stimulated by cyclic AMP and has a Km for ATP of about 0.12 mM, both in the presence and absence of cyclic AMP. By contrast, the phosphorylation of protein-bound histidine is unaffected by cyclic AMP and does not follow Michaelis-Menton kinetics since a non-linear double reciprocal plot is given when activity is measured at various ATP concentrations."}
{"id": "PMID:207325", "title": "Plasma membrane cyclic AMP-dependent protein phosphorylation system in L6 myoblasts.", "content": "Plasma membranes can be isolated without disruption of cells by the plasma membrane vesiculation technique (Scott, R.E. (1976) Science 194, 743-745). A major advantage of this technique is that it avoids contamination of plasma membranes with intracellular membrane components. Using this method, we prepared plasma membranes from L6 myoblasts grown in tissue culture and studied the characteristics of the protein phosphorylation system. We found that these plasma membrane preparations contain protein kinase which is tightly bound to the membrane and cannot be removed by washing in EDTA or in high ionic strength salt solutions. This protein kinase activity can catalyze the phosphorylation of several exogenous substrates with decreasing efficiency as acceptors of phosphate: calf thymus histones f2b, protamine and caseine. Cyclic AMP causes a dose-dependent stimulation of protein kinase activity; the highest stimulation (4-fold) is achieved at concentration 10(-5) M cyclic AMP. Cyclic AMP-dependent stimulation can be completely inhibited by heat-stable protein kinase inhibitor isolated from rabbit skeletal muscle. On the other hand, cyclic GMP does not affect the activity of protein kinase. Plasma membrane-bound protein kinase also catalyzes the phosphorylation of endogenous membrane protein substrates and this is also stimulated by addition of cyclic AMP. Analysis of plasma membrane proteins by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis showed that specific polypeptides are phosphorylated by cyclic AMP-independent and by cyclic AMP-dependent protein kinase systems. The results of these studies demonstrate the presence of endogenous cyclic AMP-dependent and -independent protein phosphorylating systems (enzyme activity and substrates) in purified plasma membrane preparations. These data provide a basis for further investigations on the role of plasma membrane phosphorylation as a regulator of membrane functions including those that may control cellular differentiation.", "contents": "Plasma membrane cyclic AMP-dependent protein phosphorylation system in L6 myoblasts. Plasma membranes can be isolated without disruption of cells by the plasma membrane vesiculation technique (Scott, R.E. (1976) Science 194, 743-745). A major advantage of this technique is that it avoids contamination of plasma membranes with intracellular membrane components. Using this method, we prepared plasma membranes from L6 myoblasts grown in tissue culture and studied the characteristics of the protein phosphorylation system. We found that these plasma membrane preparations contain protein kinase which is tightly bound to the membrane and cannot be removed by washing in EDTA or in high ionic strength salt solutions. This protein kinase activity can catalyze the phosphorylation of several exogenous substrates with decreasing efficiency as acceptors of phosphate: calf thymus histones f2b, protamine and caseine. Cyclic AMP causes a dose-dependent stimulation of protein kinase activity; the highest stimulation (4-fold) is achieved at concentration 10(-5) M cyclic AMP. Cyclic AMP-dependent stimulation can be completely inhibited by heat-stable protein kinase inhibitor isolated from rabbit skeletal muscle. On the other hand, cyclic GMP does not affect the activity of protein kinase. Plasma membrane-bound protein kinase also catalyzes the phosphorylation of endogenous membrane protein substrates and this is also stimulated by addition of cyclic AMP. Analysis of plasma membrane proteins by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis showed that specific polypeptides are phosphorylated by cyclic AMP-independent and by cyclic AMP-dependent protein kinase systems. The results of these studies demonstrate the presence of endogenous cyclic AMP-dependent and -independent protein phosphorylating systems (enzyme activity and substrates) in purified plasma membrane preparations. These data provide a basis for further investigations on the role of plasma membrane phosphorylation as a regulator of membrane functions including those that may control cellular differentiation."}
{"id": "PMID:207326", "title": "A spectroscopic and electron microscopic examination of the highly condensed DNA structures formed by denaturation in Mg(ClO4)2.", "content": "1. Thermal denaturation in 1.5 M Mg(ClO4)2 of the  DNA from bacteriophage lambda results in four well-separated subtransitions, as monitored by the accompanying increase in absorbance. The midpoint of the hyperchromic spectrum is significantly lowered compared to either 1.5 M MgCl2 or 3.0 M NaClO4. 2. The first two subtransitions are associated with the melting of the A . T-richest regions of the lambda DNA, as revealed by electron micrographs following fixation with formaldehyde. 3. Commencing with the third subtransition, an unusual DNA structure is observed in electron micrographs. In this structure the A . T-rich half of the molecule appears completely condensed, whereas the G . C-rich half remains native. 4. During the fourth subtransition DNA molecules condense completely and eventually aggregate to form extremely high molecular weight particles containing centers of electron density. Tendrils of DNA, primarily duplex, radiate outward from these centers. 5. The aggregation may be reversed by the removal of magnesium. The intramolecular condensation may be at least partly reversed by increasing the Mg(ClO4)2 concentrations to saturating levels.", "contents": "A spectroscopic and electron microscopic examination of the highly condensed DNA structures formed by denaturation in Mg(ClO4)2. 1. Thermal denaturation in 1.5 M Mg(ClO4)2 of the  DNA from bacteriophage lambda results in four well-separated subtransitions, as monitored by the accompanying increase in absorbance. The midpoint of the hyperchromic spectrum is significantly lowered compared to either 1.5 M MgCl2 or 3.0 M NaClO4. 2. The first two subtransitions are associated with the melting of the A . T-richest regions of the lambda DNA, as revealed by electron micrographs following fixation with formaldehyde. 3. Commencing with the third subtransition, an unusual DNA structure is observed in electron micrographs. In this structure the A . T-rich half of the molecule appears completely condensed, whereas the G . C-rich half remains native. 4. During the fourth subtransition DNA molecules condense completely and eventually aggregate to form extremely high molecular weight particles containing centers of electron density. Tendrils of DNA, primarily duplex, radiate outward from these centers. 5. The aggregation may be reversed by the removal of magnesium. The intramolecular condensation may be at least partly reversed by increasing the Mg(ClO4)2 concentrations to saturating levels."}
{"id": "PMID:207327", "title": "Poly(A) polymerase activity during cell cycle and erythropoietic differentiation in erythroleukemic mouse spleen cells.", "content": "Poly(A) polymerase activity was studied in lysates of cultured murine erythroleukemic cells (Friend cells). Incorporation of ATP into acid-precipitable products is dependendent on the presence of Mn2+ or Mg2+ and of an RNA primer. The reaction is specific for ATP as the substrate (KM=290 290 micron, it is not inhibited by actinomycin D and only slightly interferred with by ethidium bromide. Cordycepin 5'-triphosphate and sodium pyrophosphate inhibit the enzyme activity. The chain length of the products of the reaction is dependent on the primer concentration and reaches up to 30 nucleotides. Poly(A) polymerase activity is low in resting (G1 phase) cells 75 nmol ATP incorporated/h per 10(6) cells) and increases to a level about twice as high in early S phase of the cell cycle. A possible model for regulation of enzyme activity is discussed. Polymerase activity in the early phase of erythropoietic differentiation of the cells induced by butyric acid does not show any difference in comparison to untreated controls. A decrease in enzyme activity to levels characteristic for cells in G1 phase accompanies shutdown of cell growth in the course of the ongoing differentiation. Analysis of the DNA content of the cells revealed that erythropoietic differentiation of Friend cells induced by butyric acid is characterized by arrest of the cells in G1 phase of the cell cycle. Poly(A) polymerase activity in erythroleukemic cells is thus controlled only by the phase of the cell cycle; it is not affected by changes in gene expression during erythroid differentiation.", "contents": "Poly(A) polymerase activity during cell cycle and erythropoietic differentiation in erythroleukemic mouse spleen cells. Poly(A) polymerase activity was studied in lysates of cultured murine erythroleukemic cells (Friend cells). Incorporation of ATP into acid-precipitable products is dependendent on the presence of Mn2+ or Mg2+ and of an RNA primer. The reaction is specific for ATP as the substrate (KM=290 290 micron, it is not inhibited by actinomycin D and only slightly interferred with by ethidium bromide. Cordycepin 5'-triphosphate and sodium pyrophosphate inhibit the enzyme activity. The chain length of the products of the reaction is dependent on the primer concentration and reaches up to 30 nucleotides. Poly(A) polymerase activity is low in resting (G1 phase) cells 75 nmol ATP incorporated/h per 10(6) cells) and increases to a level about twice as high in early S phase of the cell cycle. A possible model for regulation of enzyme activity is discussed. Polymerase activity in the early phase of erythropoietic differentiation of the cells induced by butyric acid does not show any difference in comparison to untreated controls. A decrease in enzyme activity to levels characteristic for cells in G1 phase accompanies shutdown of cell growth in the course of the ongoing differentiation. Analysis of the DNA content of the cells revealed that erythropoietic differentiation of Friend cells induced by butyric acid is characterized by arrest of the cells in G1 phase of the cell cycle. Poly(A) polymerase activity in erythroleukemic cells is thus controlled only by the phase of the cell cycle; it is not affected by changes in gene expression during erythroid differentiation."}
{"id": "PMID:207328", "title": "Identification of mitochondrial gene products by DNA-directed protein synthesis in vitro.", "content": "1. A cell-free system, derived from Escherichia coli is highly active in the linked transcription-translation of yeast mtDNA from both wild-type and petite strains. 2. The products of synthesis are short (Mr less than 10 000) hydrophobic polypeptides, which show a high tendency to aggregate in a specific fashion with E. coli and mitochondrial proteins. Aggregation is extremely persistent: alkali, sodium dodecyl sulphate/urea, guanidinium . HCl and carboxymethylation reduce it, but do not eliminate it completely. 3. Nevertheless, results of indirect immunoprecipitation tests suggest that antigenic determinants of cytochrome c oxidase are among the products synthesized. The immunoprecipitation appears specific by criteria including competition experiments and its absence when mtDNA from low complexity petites, retaining only the gene for 21 S rRNA and some flanking sequences, is used to programme protein synthesis. Electrophoretic analysis of material precipitated by anti-cytochrome c oxidase sera reveals four discrete polypeptides with molecular weights of 7400, 6400, 5000 and 4100, which probably represent polypeptide fragments carrying antigenic determinants of cytochrome c oxidase.", "contents": "Identification of mitochondrial gene products by DNA-directed protein synthesis in vitro. 1. A cell-free system, derived from Escherichia coli is highly active in the linked transcription-translation of yeast mtDNA from both wild-type and petite strains. 2. The products of synthesis are short (Mr less than 10 000) hydrophobic polypeptides, which show a high tendency to aggregate in a specific fashion with E. coli and mitochondrial proteins. Aggregation is extremely persistent: alkali, sodium dodecyl sulphate/urea, guanidinium . HCl and carboxymethylation reduce it, but do not eliminate it completely. 3. Nevertheless, results of indirect immunoprecipitation tests suggest that antigenic determinants of cytochrome c oxidase are among the products synthesized. The immunoprecipitation appears specific by criteria including competition experiments and its absence when mtDNA from low complexity petites, retaining only the gene for 21 S rRNA and some flanking sequences, is used to programme protein synthesis. Electrophoretic analysis of material precipitated by anti-cytochrome c oxidase sera reveals four discrete polypeptides with molecular weights of 7400, 6400, 5000 and 4100, which probably represent polypeptide fragments carrying antigenic determinants of cytochrome c oxidase."}
{"id": "PMID:207329", "title": "The effect of different buffers on terminal deoxynucleotidyl transferase activity.", "content": "The polymerization of dATP, dCTP, and dGTP onto the defined length initiator, d(pA)10, has been carried out in four buffers. The relative effectiveness of the buffers for the polymerization of each deoxynucleoside triphosphate decreased in the order: cacodylate, 2(N-morpholino)ethane sulfonic acid, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, and Tris. With the poorer buffers, activity could be increased by the addition of KCl: this effect is not primarily due to an increase in ionic strength. With dGTP as the substrate, but not with dATP or dCTP, activity increased when the concentration of the more active buffers was raised beyond 0.2 M.", "contents": "The effect of different buffers on terminal deoxynucleotidyl transferase activity. The polymerization of dATP, dCTP, and dGTP onto the defined length initiator, d(pA)10, has been carried out in four buffers. The relative effectiveness of the buffers for the polymerization of each deoxynucleoside triphosphate decreased in the order: cacodylate, 2(N-morpholino)ethane sulfonic acid, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, and Tris. With the poorer buffers, activity could be increased by the addition of KCl: this effect is not primarily due to an increase in ionic strength. With dGTP as the substrate, but not with dATP or dCTP, activity increased when the concentration of the more active buffers was raised beyond 0.2 M."}
{"id": "PMID:207330", "title": "Kinetic mechanism of the hydroxypyruvate-lactate dehydrogenase-NADH system.", "content": "Chicken liver lactate dehydrogenase L-lactate : NAD+ oxidoreductase, EC1.1.1.27) reversibly catalyses the conversion of hydroxypyruvate to L-glycerate. The variation of the initial reaction rate with the substrate or coenzyme (NADH) concentration together with the inhibition caused by the reaction products and excess substrates, reveal that the kinetic mechanism of the reaction, with hydroxypyruvate as substrate, is of the rapid-equilibrium, ordered-ternary-complex type; NADH is the first substrate in the reaction sequence. Rate equations have been developed for the hydroxypyruvate.E.NADH system without inhibitors, with excess substrates, and with reaction products. Comparison of the rate equations obtained with those calculated theoretically from an ordered-ternary-complex mechanism reveals the existence of E.NAD.NADH,E.NAD-hydroxypyruvate and E.hydroxypyruvate complexes.", "contents": "Kinetic mechanism of the hydroxypyruvate-lactate dehydrogenase-NADH system. Chicken liver lactate dehydrogenase L-lactate : NAD+ oxidoreductase, EC1.1.1.27) reversibly catalyses the conversion of hydroxypyruvate to L-glycerate. The variation of the initial reaction rate with the substrate or coenzyme (NADH) concentration together with the inhibition caused by the reaction products and excess substrates, reveal that the kinetic mechanism of the reaction, with hydroxypyruvate as substrate, is of the rapid-equilibrium, ordered-ternary-complex type; NADH is the first substrate in the reaction sequence. Rate equations have been developed for the hydroxypyruvate.E.NADH system without inhibitors, with excess substrates, and with reaction products. Comparison of the rate equations obtained with those calculated theoretically from an ordered-ternary-complex mechanism reveals the existence of E.NAD.NADH,E.NAD-hydroxypyruvate and E.hydroxypyruvate complexes."}
{"id": "PMID:207331", "title": "Purification of beef-heart cytochrome c oxidase by hydrophobic interaction chromatography on octyl-Sepharose CL-4B.", "content": "1. Hydrophobic interaction chromatography on Octyl-Sepharose CL-4B is used as a new and simple method for the preparation of large amounts of beef-heart cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). 2. The method involves only one cycle of (NH4)2SO4 fractionation before the material is applied to the column. After washing with 10% cholate and 1.5% Tween 80, elution of the enzyme is accomplished with 1% Triton X-100. 3. The enzyme so prepared contains about 10 nmol heme alpha/mg protein and about 0.2% phospholipid. 4. Characterization of the enzyme has been made with optical and EPR spectroscopy and polyacrylamide gel electrophoresis. The preparation appears by these criteria to be at least as good as other purified enzyme preparations. 5. The turnover rate at infinite cytochrome c concentration in 0.1 M sodium phosphate buffer and 0.5% Tween 80 at pH 6.1 is 80 s-1 per functional unit of the enzyme. A more than three-fold activation could be obtained by the addition of phosphatidylcholine at neutral pH.", "contents": "Purification of beef-heart cytochrome c oxidase by hydrophobic interaction chromatography on octyl-Sepharose CL-4B. 1. Hydrophobic interaction chromatography on Octyl-Sepharose CL-4B is used as a new and simple method for the preparation of large amounts of beef-heart cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). 2. The method involves only one cycle of (NH4)2SO4 fractionation before the material is applied to the column. After washing with 10% cholate and 1.5% Tween 80, elution of the enzyme is accomplished with 1% Triton X-100. 3. The enzyme so prepared contains about 10 nmol heme alpha/mg protein and about 0.2% phospholipid. 4. Characterization of the enzyme has been made with optical and EPR spectroscopy and polyacrylamide gel electrophoresis. The preparation appears by these criteria to be at least as good as other purified enzyme preparations. 5. The turnover rate at infinite cytochrome c concentration in 0.1 M sodium phosphate buffer and 0.5% Tween 80 at pH 6.1 is 80 s-1 per functional unit of the enzyme. A more than three-fold activation could be obtained by the addition of phosphatidylcholine at neutral pH."}
{"id": "PMID:207332", "title": "Oscillatory kinetics of the peroxidase-oxidase reaction in an open system. Experimental and theoretical studies.", "content": "1. The oscillations in the peroxidase (donor: hydrogen-peroxide oxidoreductase, EC 1.11.1.7)-catalyzed reaction between NADH and O2 are undamped when the reaction is carried out in a system open to both substrates and when 2,4-dichlorophenol and methylene blue are present in the solution. 2. The waveform of the oscillations changes when the concentration of peroxidase is varied. 3. The waveforms obtained experimentally can be simulated by a branched chain reaction model in which the branching is quadratic. 4. A correlation between the present knowledge of the reaction and the model can be made by combining well established and hypothetical reaction steps into a few reaction schemes. A selection among schemes however, is not possible at the present time. 5. Compound III participates in the reaction as an active intermediate. This is possible because dichlorophenol stimulates the break down of compound III.", "contents": "Oscillatory kinetics of the peroxidase-oxidase reaction in an open system. Experimental and theoretical studies. 1. The oscillations in the peroxidase (donor: hydrogen-peroxide oxidoreductase, EC 1.11.1.7)-catalyzed reaction between NADH and O2 are undamped when the reaction is carried out in a system open to both substrates and when 2,4-dichlorophenol and methylene blue are present in the solution. 2. The waveform of the oscillations changes when the concentration of peroxidase is varied. 3. The waveforms obtained experimentally can be simulated by a branched chain reaction model in which the branching is quadratic. 4. A correlation between the present knowledge of the reaction and the model can be made by combining well established and hypothetical reaction steps into a few reaction schemes. A selection among schemes however, is not possible at the present time. 5. Compound III participates in the reaction as an active intermediate. This is possible because dichlorophenol stimulates the break down of compound III."}
{"id": "PMID:207333", "title": "Regulation of cyclic nucleotide phosphodiesterase activity in human lung fibroblasts.", "content": "Cyclic nucleotide phosphodiesterase activity (3', 5'-cyclic-nucleotide 5'-nucleotidohydrolase, 3.1.2.17) was studied in homogenates of WI-38 human lung fibroblasts using 0.1--200 microgram cyclic nucleotides. Activities were observed with low Km for cyclic AMP(2--5 micron) and low Km for cyclic GMP (1--2 micron) as well as with high Km values for cyclic AMP (100--125 micron) and cyclic GMP (75--100 micron). An increased low Km cyclic AMP phosphodiesterase activity was found upon exposure of intact fibroblasts to 3-isobutyl-1-methylxanthine, an inhibitor of phosphodiesterase activity in broken cell preparations, as well as to other agents which elevate cyclic AMP levels in these cells. The enhanced activity following exposure to 3-isobutyl-1-methylxanthine was selective for the low Km cyclic AMP phosphodiesterase since there was no change in activity of low Km cyclic GMP phosphodiesterase activity or in high Km phosphodiesterase activity with either nucleotide as substrate. The enhanced activity due to 3-isobutyl-1-methylxanthine appeared to involve de novo synthesis of a protein with short half-life (30 min), based on experiments involving cycloheximide and actinomycin D. This activity was also enhanced with increased cell density and by decreasing serum concentration. Studies of some biochemical properties and subcellular distribution of the enzyme indicated that the induced enzyme was similar to the non-induced (basal) low Km cyclic AMP phosphodiesterase.", "contents": "Regulation of cyclic nucleotide phosphodiesterase activity in human lung fibroblasts. Cyclic nucleotide phosphodiesterase activity (3', 5'-cyclic-nucleotide 5'-nucleotidohydrolase, 3.1.2.17) was studied in homogenates of WI-38 human lung fibroblasts using 0.1--200 microgram cyclic nucleotides. Activities were observed with low Km for cyclic AMP(2--5 micron) and low Km for cyclic GMP (1--2 micron) as well as with high Km values for cyclic AMP (100--125 micron) and cyclic GMP (75--100 micron). An increased low Km cyclic AMP phosphodiesterase activity was found upon exposure of intact fibroblasts to 3-isobutyl-1-methylxanthine, an inhibitor of phosphodiesterase activity in broken cell preparations, as well as to other agents which elevate cyclic AMP levels in these cells. The enhanced activity following exposure to 3-isobutyl-1-methylxanthine was selective for the low Km cyclic AMP phosphodiesterase since there was no change in activity of low Km cyclic GMP phosphodiesterase activity or in high Km phosphodiesterase activity with either nucleotide as substrate. The enhanced activity due to 3-isobutyl-1-methylxanthine appeared to involve de novo synthesis of a protein with short half-life (30 min), based on experiments involving cycloheximide and actinomycin D. This activity was also enhanced with increased cell density and by decreasing serum concentration. Studies of some biochemical properties and subcellular distribution of the enzyme indicated that the induced enzyme was similar to the non-induced (basal) low Km cyclic AMP phosphodiesterase."}
{"id": "PMID:207335", "title": "Dipeptidyl carboxypeptidase from human seminal plasma.", "content": "Dipeptidyl carboxypeptidase (angiotensin I converting enzyme) was purified from human seminal plasma. The apparent relative molecular mass determined by gel filtration on Sephadex G-200 was 330 000. The pI in isoelectric focusing was 4.6--5.0 and the optimum pH 7.7--8.0. The enzyme is activated by chloride. These properties are similar to those reported for the lung enzyme. The specificity is that of a carboxypeptidase releasing dipeptides. A study of different substrates showed the activity to be highest with Z-Leu-Gly-Gly, followed by Z-Phe-His-Leu greater than bradykinin greater than Bz-Gly-Gly-Gly greater than Boc-Phe-Ala-Pro greater than Bz-Gly-His-Leu greater than angiotensin I.", "contents": "Dipeptidyl carboxypeptidase from human seminal plasma. Dipeptidyl carboxypeptidase (angiotensin I converting enzyme) was purified from human seminal plasma. The apparent relative molecular mass determined by gel filtration on Sephadex G-200 was 330 000. The pI in isoelectric focusing was 4.6--5.0 and the optimum pH 7.7--8.0. The enzyme is activated by chloride. These properties are similar to those reported for the lung enzyme. The specificity is that of a carboxypeptidase releasing dipeptides. A study of different substrates showed the activity to be highest with Z-Leu-Gly-Gly, followed by Z-Phe-His-Leu greater than bradykinin greater than Bz-Gly-Gly-Gly greater than Boc-Phe-Ala-Pro greater than Bz-Gly-His-Leu greater than angiotensin I."}
{"id": "PMID:207336", "title": "Selective precipitation of 32Pi onto filter papers. Application to ATPase and cyclic AMP phosphodiesterase determination.", "content": "A simple and selective method is described for the isolation of 32Pi based on the precipitation of the phosphomolybdate complex with triethylamine. Precipitation takes place on filter paper, which are then washed with a solution containing ammonium molybdate and triethylamine to remove other radioactive phosphates. Very large numbers of samples and very small sample volumes can be accommodated easily. The use of this method to measure ATPase and cyclic AMP phosphodiesterase activity is demonstrated.", "contents": "Selective precipitation of 32Pi onto filter papers. Application to ATPase and cyclic AMP phosphodiesterase determination. A simple and selective method is described for the isolation of 32Pi based on the precipitation of the phosphomolybdate complex with triethylamine. Precipitation takes place on filter paper, which are then washed with a solution containing ammonium molybdate and triethylamine to remove other radioactive phosphates. Very large numbers of samples and very small sample volumes can be accommodated easily. The use of this method to measure ATPase and cyclic AMP phosphodiesterase activity is demonstrated."}
{"id": "PMID:207337", "title": "Iron: a possible heterotropic effector of prolyl hydroxylase.", "content": "The mechanism of ferrous ion binding to prolyl hydroxylase (prolyl-glycyl-peptide,2-oxoglutarate:oxygen oxidoreductase, EC 1.14.11.2) was studied according to Koshland's curve-fitting procedure (Cornish-Bowden, A. and Koshland, Jr., D.E. (1970) Biochemistry 9, 3325--3336). The calculated data obtained by means of the unrestricted Adair equation were found to provide an adequate fit with experimentally obtained values, whereas those obtained on the basis of Michaelis-Menten kinetics did not. This suggests that prolyl hydroxylase could be an allosteric enzyme under positive heterotropic control.", "contents": "Iron: a possible heterotropic effector of prolyl hydroxylase. The mechanism of ferrous ion binding to prolyl hydroxylase (prolyl-glycyl-peptide,2-oxoglutarate:oxygen oxidoreductase, EC 1.14.11.2) was studied according to Koshland's curve-fitting procedure (Cornish-Bowden, A. and Koshland, Jr., D.E. (1970) Biochemistry 9, 3325--3336). The calculated data obtained by means of the unrestricted Adair equation were found to provide an adequate fit with experimentally obtained values, whereas those obtained on the basis of Michaelis-Menten kinetics did not. This suggests that prolyl hydroxylase could be an allosteric enzyme under positive heterotropic control."}
{"id": "PMID:207338", "title": "Pilot scale purification of alpha-galactosidase A from Cohn fraction IV-1 of human plasma.", "content": "Human plasma alpha-galactosidase A (alpha-D-galactoside galactohydrolase, EC 3.2.1.22) was purified 7000-fold over plasma levels from Cohn Fraction IV-1. The yield per kg starting material averaged 11 000 units (nmol galactose liberated per h) and the specific activity was about 600 units per mg protein with 4-methylumbelliferyl-alpha-D-galactoside. The ratio of 4-methylumbelliferyl-alpha-galactosidase to ceramide trihexosidase activities was 6.2. Both activities were heat labile and exhibited the same relative mobilities on polyacrylamide gel electrophoresis. Enzymatic activity was stable for at least 4 months at 4 and -20 degrees C. The endotoxin concentration of this preparation averaged 0.26 mg per mg protein.", "contents": "Pilot scale purification of alpha-galactosidase A from Cohn fraction IV-1 of human plasma. Human plasma alpha-galactosidase A (alpha-D-galactoside galactohydrolase, EC 3.2.1.22) was purified 7000-fold over plasma levels from Cohn Fraction IV-1. The yield per kg starting material averaged 11 000 units (nmol galactose liberated per h) and the specific activity was about 600 units per mg protein with 4-methylumbelliferyl-alpha-D-galactoside. The ratio of 4-methylumbelliferyl-alpha-galactosidase to ceramide trihexosidase activities was 6.2. Both activities were heat labile and exhibited the same relative mobilities on polyacrylamide gel electrophoresis. Enzymatic activity was stable for at least 4 months at 4 and -20 degrees C. The endotoxin concentration of this preparation averaged 0.26 mg per mg protein."}
{"id": "PMID:207339", "title": "Specific cleavage of reduced and S-carboxamidomethylated neurophysin II by the collagenase of Clostridium histolyticum.", "content": "Purified collagenase of Clostridium histolyticum was shown to cleave reduced and S-carboxamidomethylated bovine neurophysin between Cys-13 and Gly-14. The scission resulted in formation of two separable fragments: a smaller peptide arising from residues 1 through 13, and a larger peptide comprising the remainder of the residues of the protein. By dansylation procedures, the smaller peptide was shown to have amino-terminal alanine as expected from the sequence of neurophysin II, and the larger peptide had amino-terminal glycine as anticipated. These results show that collagenase indeed cleaves bovine neurophysin II in accord with the specificity postulated for that enzyme, i.e., scission between -X-Gly- in a sequence of -Pro-X-Gly-Pro-Y-. This result, obtained with a non-collagenous protein substrate, is further confirmation of the specificity of collagenase as established by its action on collagens and on synthetic oligopeptides.", "contents": "Specific cleavage of reduced and S-carboxamidomethylated neurophysin II by the collagenase of Clostridium histolyticum. Purified collagenase of Clostridium histolyticum was shown to cleave reduced and S-carboxamidomethylated bovine neurophysin between Cys-13 and Gly-14. The scission resulted in formation of two separable fragments: a smaller peptide arising from residues 1 through 13, and a larger peptide comprising the remainder of the residues of the protein. By dansylation procedures, the smaller peptide was shown to have amino-terminal alanine as expected from the sequence of neurophysin II, and the larger peptide had amino-terminal glycine as anticipated. These results show that collagenase indeed cleaves bovine neurophysin II in accord with the specificity postulated for that enzyme, i.e., scission between -X-Gly- in a sequence of -Pro-X-Gly-Pro-Y-. This result, obtained with a non-collagenous protein substrate, is further confirmation of the specificity of collagenase as established by its action on collagens and on synthetic oligopeptides."}
{"id": "PMID:207340", "title": "Isolation procedure and some properties of myeloperoxidase from human leucocytes.", "content": "1. A rapid isolation procedure with a high yield for pure myeloperoxidase (donor:H2O2 oxidoreductase, EC 1.11.1.7) from normal human leucocytes is described. The enzyme was solubilized from leucocytes with the detergent, cetyltrimethylammonium bromide, and purified to apparent homogeneity. The yield of the enzyme was 17% with an absorbance ratio A430nm/A280nm = 0.85. 2. The purified enzyme showed three isoenzyme bands after polyacrylamide gel electrophoresis; ultracentrifuge studies indicated one homogeneous band with a molecular weight of 144 000. After reduction of myeloperoxidase, sodium dodecyl sulfate gel electrophoresis resolved an intense band (63 000 daltons) and a weak band (81 000 daltons). 3. The carbohydrate content of the enzyme was at least 2.5%. Mannose, glucose and N-acetylglucosamine were present. The amino acid composition is reported. 4. The EPR spectrum exhibited a high-spin heme signal with rhombic symmetry (gx = 6.92, gy = 5.07 and gz = 1.95). Upon acidification this signal was converted into a signal with more axial symmetry (g perpendicular = 5.89). At high pH (9.5) the EPR spectrum of the enzyme only shows low-spin ferric heme resonances. The circular dichroism spectra of ferric and ferrous myeloperoxidase in the visible and ultraviolet region show maxima and minima in ellipticity.", "contents": "Isolation procedure and some properties of myeloperoxidase from human leucocytes. 1. A rapid isolation procedure with a high yield for pure myeloperoxidase (donor:H2O2 oxidoreductase, EC 1.11.1.7) from normal human leucocytes is described. The enzyme was solubilized from leucocytes with the detergent, cetyltrimethylammonium bromide, and purified to apparent homogeneity. The yield of the enzyme was 17% with an absorbance ratio A430nm/A280nm = 0.85. 2. The purified enzyme showed three isoenzyme bands after polyacrylamide gel electrophoresis; ultracentrifuge studies indicated one homogeneous band with a molecular weight of 144 000. After reduction of myeloperoxidase, sodium dodecyl sulfate gel electrophoresis resolved an intense band (63 000 daltons) and a weak band (81 000 daltons). 3. The carbohydrate content of the enzyme was at least 2.5%. Mannose, glucose and N-acetylglucosamine were present. The amino acid composition is reported. 4. The EPR spectrum exhibited a high-spin heme signal with rhombic symmetry (gx = 6.92, gy = 5.07 and gz = 1.95). Upon acidification this signal was converted into a signal with more axial symmetry (g perpendicular = 5.89). At high pH (9.5) the EPR spectrum of the enzyme only shows low-spin ferric heme resonances. The circular dichroism spectra of ferric and ferrous myeloperoxidase in the visible and ultraviolet region show maxima and minima in ellipticity."}
{"id": "PMID:207341", "title": "Phosphorylation of rat kidney pyruvate kinase type L by cyclic 3',5'-AMP-dependent protein kinase.", "content": "Pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) type L was partly purified from rat kidney. During the last two purification steps, the incorporation of [32P]phosphate into protein on incubation with [32P]ATP and cyclic 3',5'-AMP-dependent protein kinase was found to parallel the pyruvate kinase activity. After phosphorylation of the enzyme, a major radioactive band with a molecular weight of 57 000 was found on polyacrylamide gel electrophoresis [32P]Phosphorylserine was isolated from the kidney pyruvate kinase. Immunological identity was found between the liver and kidney pyruvate kinases type L. By autoradiography of high-voltage electropherograms after partial acid hydrolysis of the phosphorylated rat liver and kidney pyruvate kinases type L, identical results were obtained. The affinity for phosphoenolpyruvate was found to be decreased by phosphorylation of the enzyme with a change in the apparent Km from 0.15 mM to 0.35 mM. After incubation of the phosphorylated kidney pyruvate kinase with phosphatase the phosphoenolpyruvate saturation curve was found to be identical to that for the unphosphorylated enzyme. Thus, the activity of the rat kidney pyruvate kinase type L is with all probability regulated by a reversible phosphorylation-dephosphorylation reaction, thereby indicating that hormonal regulation of gluconeogenesis via cyclic AMP may be of importance in the renal cortex.", "contents": "Phosphorylation of rat kidney pyruvate kinase type L by cyclic 3',5'-AMP-dependent protein kinase. Pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) type L was partly purified from rat kidney. During the last two purification steps, the incorporation of [32P]phosphate into protein on incubation with [32P]ATP and cyclic 3',5'-AMP-dependent protein kinase was found to parallel the pyruvate kinase activity. After phosphorylation of the enzyme, a major radioactive band with a molecular weight of 57 000 was found on polyacrylamide gel electrophoresis [32P]Phosphorylserine was isolated from the kidney pyruvate kinase. Immunological identity was found between the liver and kidney pyruvate kinases type L. By autoradiography of high-voltage electropherograms after partial acid hydrolysis of the phosphorylated rat liver and kidney pyruvate kinases type L, identical results were obtained. The affinity for phosphoenolpyruvate was found to be decreased by phosphorylation of the enzyme with a change in the apparent Km from 0.15 mM to 0.35 mM. After incubation of the phosphorylated kidney pyruvate kinase with phosphatase the phosphoenolpyruvate saturation curve was found to be identical to that for the unphosphorylated enzyme. Thus, the activity of the rat kidney pyruvate kinase type L is with all probability regulated by a reversible phosphorylation-dephosphorylation reaction, thereby indicating that hormonal regulation of gluconeogenesis via cyclic AMP may be of importance in the renal cortex."}
{"id": "PMID:207342", "title": "Regulatory role of insulin in the degradation of low density lipoprotein by cultured human skin fibroblasts.", "content": "The degradation of 125I-labeled low density lipoprotein by cultured human skin fibroblasts was enhanced 25% by preincubation of cells with insulin. This effect of insulin appeared to be mediated via stimulation of low density lipoprotein binding to its cell surface receptor, since binding and subsequent internalization of low density lipoprotein were stimulated to a similar extent as was degradation. In addition, insulin enhanced binding of low density lipoprotein at 4 degrees C, at which temperature internalization of the lipoprotein does not occur. A similar effect of insulin on the interaction of very low density lipoprotein with cultured fibroblasts was observed. Insulin-induced changes in the degradation of low density lipoprotein and very low density lipoprotein appeared to be a function of the change in lipoprotein binding. Thus, insulin may play a role in the regulation of low density lipoprotein and very low density lipoprotein degradation by peripheral cells by influencing the receptor-mediated transport of these lipoproteins.", "contents": "Regulatory role of insulin in the degradation of low density lipoprotein by cultured human skin fibroblasts. The degradation of 125I-labeled low density lipoprotein by cultured human skin fibroblasts was enhanced 25% by preincubation of cells with insulin. This effect of insulin appeared to be mediated via stimulation of low density lipoprotein binding to its cell surface receptor, since binding and subsequent internalization of low density lipoprotein were stimulated to a similar extent as was degradation. In addition, insulin enhanced binding of low density lipoprotein at 4 degrees C, at which temperature internalization of the lipoprotein does not occur. A similar effect of insulin on the interaction of very low density lipoprotein with cultured fibroblasts was observed. Insulin-induced changes in the degradation of low density lipoprotein and very low density lipoprotein appeared to be a function of the change in lipoprotein binding. Thus, insulin may play a role in the regulation of low density lipoprotein and very low density lipoprotein degradation by peripheral cells by influencing the receptor-mediated transport of these lipoproteins."}
{"id": "PMID:207344", "title": "Surface exposure of apolipoproteins in high density lipoproteins. I. Reactivities with agarose-immobilized proteases.", "content": "The exposure of apolipoproteins at the surface of human plasma high density lipoproteins (HDL) was assessed by their accessibility to agarose-immobilized forms of trypsin and chymotrypsin. Proteolysis of lipid-free apolipoproteins and the lipoprotein subfractions HDL2 (d = 1.08--1.125 g/ml) and HDL3 (d = 1.125--1.195 g/ml) that differ in lipid-to-protein ratio was compared by polyacrylamide gel electrophoresis and isoelectric focusing of the apolipoproteins and peptide fragments and by quantitation of the various carboxyl-terminal groups formed. Gel filtration of the proteolyzed lipoproteins on Sephadex G-150 column indicated that more than 90% of the apolipoproteins and peptides remain associated with lipoprotein complexes. Proteolysis of lipoproteins occurred more slowly and with less fragmentation of the lipoproteins and apolipoproteins than proteolysis of thelipid-free apolipoproteins or the proteolysis of lipoproteins by soluble proteases reported by other investigators. The difference in lipid content of HDL2 and HDL3 made little difference in their proteolysis. Proteolysis of the lipoproteins by agarose-trypsin was more rapid at 37 degrees C than at 22 degrees C, but the proteolytic products were similar and differed from the products from the lipid free proteins. Peptide fragments from lipoproteins were larger than those from lipid-free proteins, which suggests masking of potentially cleavable groups by lipid. The amounts (mol/g protein) of new carboxyl-terminal tyrosine and phenylalanine released by agarose -chymotrypsin were much greater from the lipid-free proteins, but about 3/4 of the tryptophan residues were inacessible in both lipoproteins and lipid-free proteins. In agarose-trypsin digestion, lysine residues were slightly more masked than arginine in the absence of lipids and much more so in the lipoproteins. However, in the lipoproteins apoA-II, which contains lysine but no arginine, was cleaved more rapidly and extensively by agarose-trypsin than apoA-I.", "contents": "Surface exposure of apolipoproteins in high density lipoproteins. I. Reactivities with agarose-immobilized proteases. The exposure of apolipoproteins at the surface of human plasma high density lipoproteins (HDL) was assessed by their accessibility to agarose-immobilized forms of trypsin and chymotrypsin. Proteolysis of lipid-free apolipoproteins and the lipoprotein subfractions HDL2 (d = 1.08--1.125 g/ml) and HDL3 (d = 1.125--1.195 g/ml) that differ in lipid-to-protein ratio was compared by polyacrylamide gel electrophoresis and isoelectric focusing of the apolipoproteins and peptide fragments and by quantitation of the various carboxyl-terminal groups formed. Gel filtration of the proteolyzed lipoproteins on Sephadex G-150 column indicated that more than 90% of the apolipoproteins and peptides remain associated with lipoprotein complexes. Proteolysis of lipoproteins occurred more slowly and with less fragmentation of the lipoproteins and apolipoproteins than proteolysis of thelipid-free apolipoproteins or the proteolysis of lipoproteins by soluble proteases reported by other investigators. The difference in lipid content of HDL2 and HDL3 made little difference in their proteolysis. Proteolysis of the lipoproteins by agarose-trypsin was more rapid at 37 degrees C than at 22 degrees C, but the proteolytic products were similar and differed from the products from the lipid free proteins. Peptide fragments from lipoproteins were larger than those from lipid-free proteins, which suggests masking of potentially cleavable groups by lipid. The amounts (mol/g protein) of new carboxyl-terminal tyrosine and phenylalanine released by agarose -chymotrypsin were much greater from the lipid-free proteins, but about 3/4 of the tryptophan residues were inacessible in both lipoproteins and lipid-free proteins. In agarose-trypsin digestion, lysine residues were slightly more masked than arginine in the absence of lipids and much more so in the lipoproteins. However, in the lipoproteins apoA-II, which contains lysine but no arginine, was cleaved more rapidly and extensively by agarose-trypsin than apoA-I."}
{"id": "PMID:207345", "title": "The degradation of very low density lipoprotein by the extrahepatic tissues of the rat.", "content": "The supradiaphragmatic rat was used to investigate the metabolism by the extrahepatic tissues of endogenous plasma VLDL of d less than 1.006 g/ml. The demonstration that, at 20, 30 and 40 min after the isolation of the supradiaphragmatic rat, the VLDL lose respectively 29, 54, and 63% of their triglyceride provides evidence for the suitability of this preparation for the investigation of VLDL degradation. At all time intervals after the isolation of the supradiaphragmatic rat, VLDL triglyceride loss was accompanied by similar losses of cholesterol, protein and phospholipid, with the result that the percentage by weight composition of the residual VLDL remained unaltered. By subfractionation of the VLDL, a group of particles with an Sf range of 20--60 were isolated that, when compared with total VLDL, were enriched in their cholesterol (P less than 0.02), protein (P less than 0.001) and phospholipid (P less than 0.01) content. However, these particles represented only a small percentage of the total VLDL mass. Furthermore, their amount was not increased in the circulation of the supradiaphragmatic rat. The amount of IDL (d = 1.006--1.019 g/m) and of LDL (d = 1.019--1.063 g/ml) was increased in the supradiaphragmatic rat and a part of the total cholesterol and protein lost from the VLDL could be accounted for by the increases in these constituents in the IDL and LDL fractions. It is suggested that, although the liver probably takes up partial degradation products of VLDL in the intact animal, the extrahepatic tissues alone can metabolize VLDL to LDL of d = 1.019--1.063 g/ml. The lipoprotein particles taken up by the liver in the intact animal appear most likely to be those of Sf greater than 100.", "contents": "The degradation of very low density lipoprotein by the extrahepatic tissues of the rat. The supradiaphragmatic rat was used to investigate the metabolism by the extrahepatic tissues of endogenous plasma VLDL of d less than 1.006 g/ml. The demonstration that, at 20, 30 and 40 min after the isolation of the supradiaphragmatic rat, the VLDL lose respectively 29, 54, and 63% of their triglyceride provides evidence for the suitability of this preparation for the investigation of VLDL degradation. At all time intervals after the isolation of the supradiaphragmatic rat, VLDL triglyceride loss was accompanied by similar losses of cholesterol, protein and phospholipid, with the result that the percentage by weight composition of the residual VLDL remained unaltered. By subfractionation of the VLDL, a group of particles with an Sf range of 20--60 were isolated that, when compared with total VLDL, were enriched in their cholesterol (P less than 0.02), protein (P less than 0.001) and phospholipid (P less than 0.01) content. However, these particles represented only a small percentage of the total VLDL mass. Furthermore, their amount was not increased in the circulation of the supradiaphragmatic rat. The amount of IDL (d = 1.006--1.019 g/m) and of LDL (d = 1.019--1.063 g/ml) was increased in the supradiaphragmatic rat and a part of the total cholesterol and protein lost from the VLDL could be accounted for by the increases in these constituents in the IDL and LDL fractions. It is suggested that, although the liver probably takes up partial degradation products of VLDL in the intact animal, the extrahepatic tissues alone can metabolize VLDL to LDL of d = 1.019--1.063 g/ml. The lipoprotein particles taken up by the liver in the intact animal appear most likely to be those of Sf greater than 100."}
{"id": "PMID:207346", "title": "Studies of the cyanogen bromide fragments of the apoprotein of human serum low density lipoproteins.", "content": "The apoprotein of human serum low density lipoproteins was reduced and carboxymethylated and then cleaved by cyanogen bromide (CNBr). The peptides which were produced from this cleavage (90% yield, based upon loss of methionine) were resolved by SDS polyacrylamide gel electrophoresis into 10 major bands, each having an amino acid composition very similar to that of intact reduced and carboxymethylated LDL apoprotein. The fractionation of the CNBr fragments by preparative gel filtration was dependent upon the nature of the eluting solvent. NH4OH and SDS solvents eluted all of the material in the void volume. In 6 M guanidinium chloride solvents several peaks were, however, resolved, each having an amino acid composition similar to that of the unfractionated products. Whereas no NH2-terminal was detected in reduced and carboxylmethylated LDL apoprotein, automated Edman degradation of the protein following treatment with CNBr revealed the presence of several NH2-termini. The results suggest that LDL apoprotein may be made of segments of, at least, very similar amino acid composition and that both the protein itself and derivative fragments have a great tendency to aggregate even in denaturing solvents.", "contents": "Studies of the cyanogen bromide fragments of the apoprotein of human serum low density lipoproteins. The apoprotein of human serum low density lipoproteins was reduced and carboxymethylated and then cleaved by cyanogen bromide (CNBr). The peptides which were produced from this cleavage (90% yield, based upon loss of methionine) were resolved by SDS polyacrylamide gel electrophoresis into 10 major bands, each having an amino acid composition very similar to that of intact reduced and carboxymethylated LDL apoprotein. The fractionation of the CNBr fragments by preparative gel filtration was dependent upon the nature of the eluting solvent. NH4OH and SDS solvents eluted all of the material in the void volume. In 6 M guanidinium chloride solvents several peaks were, however, resolved, each having an amino acid composition similar to that of the unfractionated products. Whereas no NH2-terminal was detected in reduced and carboxylmethylated LDL apoprotein, automated Edman degradation of the protein following treatment with CNBr revealed the presence of several NH2-termini. The results suggest that LDL apoprotein may be made of segments of, at least, very similar amino acid composition and that both the protein itself and derivative fragments have a great tendency to aggregate even in denaturing solvents."}
{"id": "PMID:207347", "title": "Very low density lipoprotein stimulation of triglyceride accumulation in rat preadipocyte cultures.", "content": "Exposure of cultured rat epididymal preadipocytes to human very low density lipoproteins (VLDL) resulted in the rapid accumulation of large amounts of cellular triglyceride which was accompanied by the appearance of numerous large cellular lipid inclusions. Addition of heparin produced a two-fold stimulation of lipoprotein induced triglyceride accumulation. Supplementation of the growth medium with either low density lipoprotein, oleic acid or artificial triglyceride emulsion did not produce cellular triglyceride levels equivalent to that obtained with VLDL. Fibroblastic cells from rat skin and lung did not accumulate triglycerides when exposed to VLDL and heparin.", "contents": "Very low density lipoprotein stimulation of triglyceride accumulation in rat preadipocyte cultures. Exposure of cultured rat epididymal preadipocytes to human very low density lipoproteins (VLDL) resulted in the rapid accumulation of large amounts of cellular triglyceride which was accompanied by the appearance of numerous large cellular lipid inclusions. Addition of heparin produced a two-fold stimulation of lipoprotein induced triglyceride accumulation. Supplementation of the growth medium with either low density lipoprotein, oleic acid or artificial triglyceride emulsion did not produce cellular triglyceride levels equivalent to that obtained with VLDL. Fibroblastic cells from rat skin and lung did not accumulate triglycerides when exposed to VLDL and heparin."}
{"id": "PMID:207348", "title": "Affinity electrophoresis of proteins interacting with Blue dextran.", "content": "Interaction of several enzymes (pyruvate kinase, myokinase, creatine kinase, aldolase, malate dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase and glucose-6-phosphate dehydrogenase) and other proteins (bovine serum albumin and ovalbumin) with Blue Dextran was studied by means of affinity electrophoresis in polyacrylamide gels. A decrease of electrophoretic mobility of enzymes in affinity gels was dependent on Blue Dextran concentration and in some cases, dissociation constants of the protein-immobilized dye complexes could be calculated. Affinity electrophoresis in the presence of Blue Dextran reveals in some cases additional bands of isoenzymes, as compared with the control gels (without Blue Dextran).", "contents": "Affinity electrophoresis of proteins interacting with Blue dextran. Interaction of several enzymes (pyruvate kinase, myokinase, creatine kinase, aldolase, malate dehydrogenase, lactate dehydrogenase, alcohol dehydrogenase and glucose-6-phosphate dehydrogenase) and other proteins (bovine serum albumin and ovalbumin) with Blue Dextran was studied by means of affinity electrophoresis in polyacrylamide gels. A decrease of electrophoretic mobility of enzymes in affinity gels was dependent on Blue Dextran concentration and in some cases, dissociation constants of the protein-immobilized dye complexes could be calculated. Affinity electrophoresis in the presence of Blue Dextran reveals in some cases additional bands of isoenzymes, as compared with the control gels (without Blue Dextran)."}
{"id": "PMID:207349", "title": "The state of copper in Neurospora laccase.", "content": "1. Neurospora crassa laccase has been prepared from the growth medium and studied by optical absorption, circular dichroism and electron paramagnetic resonance (EPR) spectroscopy. The molecular weight, the copper content and the amino acid composition have also been determined. 2. The molecular weight as determined by gel filtration in 6 M guanidine hydrochloride and by sodium dodecyl sulfate gel electrophoresis is found to be 64 000. The enzyme contains 3.8 copper ions per 64 000. 3. The visible and the near ultraviolet difference absorption spectrum shows two maxima, at 330 and 595 nm, and a shoulder at about 720 nm. The circular dichroism spectrum between 300 and 760 nm contains five bands in the oxidized enzyme. After reduction of the enzyme with ascorbate there remains only a band at 305 nm. 4. EPR measurements show that 52% of the total copper in the protein is paramagnetic. Two EPR signals of equal intensity with different hyperfine splitting constants, of 9 and 18.5 mT, are present, which are assigned to Type 1 Cu2+ and Type 2 Cu2+, respectively, as found in other blue copper-containing oxidases.", "contents": "The state of copper in Neurospora laccase. 1. Neurospora crassa laccase has been prepared from the growth medium and studied by optical absorption, circular dichroism and electron paramagnetic resonance (EPR) spectroscopy. The molecular weight, the copper content and the amino acid composition have also been determined. 2. The molecular weight as determined by gel filtration in 6 M guanidine hydrochloride and by sodium dodecyl sulfate gel electrophoresis is found to be 64 000. The enzyme contains 3.8 copper ions per 64 000. 3. The visible and the near ultraviolet difference absorption spectrum shows two maxima, at 330 and 595 nm, and a shoulder at about 720 nm. The circular dichroism spectrum between 300 and 760 nm contains five bands in the oxidized enzyme. After reduction of the enzyme with ascorbate there remains only a band at 305 nm. 4. EPR measurements show that 52% of the total copper in the protein is paramagnetic. Two EPR signals of equal intensity with different hyperfine splitting constants, of 9 and 18.5 mT, are present, which are assigned to Type 1 Cu2+ and Type 2 Cu2+, respectively, as found in other blue copper-containing oxidases."}
{"id": "PMID:207350", "title": "Specificity of the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase and to a series of other calcium-binding proteins.", "content": "Trifluoperazine inhibits the activation of phosphodiesterase by binding to the calcium-dependent activator. To determine further the specificity by which trifluoperazine binds to activator, we compared the binding of trifluoperazine to activator prepared from several species and tissues and to a number of other calcium-binding proteins devoid of activator activity. Trifluoperazine binds to activator prepared from human, bovine, rat and rabbit brain and from chick embryo fibroblasts. In each case, the binding of trifluoperazine to activator was qualitatively similar and related quantitatively to the ability of the preparation to activate phosphodiesterase. Of the other calcium-binding proteins examined, namely, troponin-C, S-100 protein, phospholipase A, phospholipase B and myosin light chain, only troponin-C displayed any significant calcium-specific binding of trifluoperazine. The binding to troponin-C, however, appeared to be different from the binding to activator; whereas the binding of trifluoperazine to actovator showed no cooperativity, the binding to troponin-C showed positive cooperatively. These results and earlier data showing that trifluoperazine fails to bind to a variety of other proteins, indicate that the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase is selective and suggest that this binding may explain some of the biochemical and pharmacological actions of this antipsychotic agent.", "contents": "Specificity of the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase and to a series of other calcium-binding proteins. Trifluoperazine inhibits the activation of phosphodiesterase by binding to the calcium-dependent activator. To determine further the specificity by which trifluoperazine binds to activator, we compared the binding of trifluoperazine to activator prepared from several species and tissues and to a number of other calcium-binding proteins devoid of activator activity. Trifluoperazine binds to activator prepared from human, bovine, rat and rabbit brain and from chick embryo fibroblasts. In each case, the binding of trifluoperazine to activator was qualitatively similar and related quantitatively to the ability of the preparation to activate phosphodiesterase. Of the other calcium-binding proteins examined, namely, troponin-C, S-100 protein, phospholipase A, phospholipase B and myosin light chain, only troponin-C displayed any significant calcium-specific binding of trifluoperazine. The binding to troponin-C, however, appeared to be different from the binding to activator; whereas the binding of trifluoperazine to actovator showed no cooperativity, the binding to troponin-C showed positive cooperatively. These results and earlier data showing that trifluoperazine fails to bind to a variety of other proteins, indicate that the binding of trifluoperazine to the calcium-dependent activator of phosphodiesterase is selective and suggest that this binding may explain some of the biochemical and pharmacological actions of this antipsychotic agent."}
{"id": "PMID:207352", "title": "Secretion of epidermal growth factor. The role of calcium in stimulcule during secretion.", "content": "Secretion of epidermal growth factor by mouse submandibular salivary glands was studied in vitro to determine the second messenger involved in stimulus-secretion coupling and also to determine whether epidermal growth factor is secreted in the molecular form in which it occurs within the glandular cells. The presence of Ca2+ in the extracellular fluid was found to be necessary for the normal secretion of epidermal growth factor that follows activation of alpha-adrenoceptors. Dibutyryl cyclic AMP (1 mM) did not evoke any secretion of the growth factor. Secreted epidermal growth factor retained its ability to bind to anti-epidermal growth factor antibodies and to epidermal growth factor-binding sites on liver cell membranes. However, during secretion the 74 000-dalton, 4-subunit complex, in which epidermal growth facto; occurs within the cells, dissociated. The adrenalin-stimulated submandibular salivary gland did not appear to release any material into the incubation medium which could modify the complex and produce the dissociation. It is suggested that the dissociation of the high molecule containing epidermal growth factor results from the loss of the arginyl residue from the C-terminus of epidermal growth factor at some time during the secretion process.", "contents": "Secretion of epidermal growth factor. The role of calcium in stimulcule during secretion. Secretion of epidermal growth factor by mouse submandibular salivary glands was studied in vitro to determine the second messenger involved in stimulus-secretion coupling and also to determine whether epidermal growth factor is secreted in the molecular form in which it occurs within the glandular cells. The presence of Ca2+ in the extracellular fluid was found to be necessary for the normal secretion of epidermal growth factor that follows activation of alpha-adrenoceptors. Dibutyryl cyclic AMP (1 mM) did not evoke any secretion of the growth factor. Secreted epidermal growth factor retained its ability to bind to anti-epidermal growth factor antibodies and to epidermal growth factor-binding sites on liver cell membranes. However, during secretion the 74 000-dalton, 4-subunit complex, in which epidermal growth facto; occurs within the cells, dissociated. The adrenalin-stimulated submandibular salivary gland did not appear to release any material into the incubation medium which could modify the complex and produce the dissociation. It is suggested that the dissociation of the high molecule containing epidermal growth factor results from the loss of the arginyl residue from the C-terminus of epidermal growth factor at some time during the secretion process."}
{"id": "PMID:207354", "title": "Hormone action at the membrane level. VII. Stimulation of dihydroalprenolol binding to beta-adrenergic receptors in isolated rat heart ventricle slices by triiodothyronine and thyroxine.", "content": "Thyroxine (T4) and triiodothyronine (T3) increase the number of beta-adrenergic receptors in heart ventricle slices. A short term effect reaches a maximum by 1.5-2 h and requires added amino acids for consistent results. The apparent Km for the L-T3 effect is 15 pM. This effect, measured by an increase in stereospecific binding of (-)-[3H]dihydroalprenolol is not inhibited by cycloheximide or puromycin and is produced more effectively by L-T3 than D-T3. However, cycloheximide nearly completely inhibits protein synthesis in the 2-3 h incubation time. T3 also gives a small inhibition of protein synthesis during this time interval. The early effect of T3 stimulation of dihydroalprenolol binding is considered to be a post-translational event shereby T3 enhances the transport of existing beta-adrenergic receptors from the cytosol into the membrane. A long term (15 h) stimulation of dihydroalprenolol binding to ventricle membranes is also produced by L-T3. This effect is stereospecific, is inhibited by cycloheximide, and is believed to be a transcriptional-translational event leading to the synthesis of new beta-adrenergic receptors by T3.", "contents": "Hormone action at the membrane level. VII. Stimulation of dihydroalprenolol binding to beta-adrenergic receptors in isolated rat heart ventricle slices by triiodothyronine and thyroxine. Thyroxine (T4) and triiodothyronine (T3) increase the number of beta-adrenergic receptors in heart ventricle slices. A short term effect reaches a maximum by 1.5-2 h and requires added amino acids for consistent results. The apparent Km for the L-T3 effect is 15 pM. This effect, measured by an increase in stereospecific binding of (-)-[3H]dihydroalprenolol is not inhibited by cycloheximide or puromycin and is produced more effectively by L-T3 than D-T3. However, cycloheximide nearly completely inhibits protein synthesis in the 2-3 h incubation time. T3 also gives a small inhibition of protein synthesis during this time interval. The early effect of T3 stimulation of dihydroalprenolol binding is considered to be a post-translational event shereby T3 enhances the transport of existing beta-adrenergic receptors from the cytosol into the membrane. A long term (15 h) stimulation of dihydroalprenolol binding to ventricle membranes is also produced by L-T3. This effect is stereospecific, is inhibited by cycloheximide, and is believed to be a transcriptional-translational event leading to the synthesis of new beta-adrenergic receptors by T3."}
{"id": "PMID:207355", "title": "Dissociation of lutropin-induced loss of testicular lutropin receptors and lutropin-induced desensitization of testosterone synthesis.", "content": "The relationship between changes in testicular lutropin receptors, as measured by specific binding of 125I-labeled human chorionic gonadotropin, and testosterone synthesis in response to lutropin (testicular responsiveness) was studied in intact and hypophysectomized rats. Administration of a single 200-microgram dose of ovine lutropin to intact rats results at 3 days in a 58% decrease in lutropin receptors associated with a parallel decrease in testicular responsiveness. A single 30-microgram dose of lutropin to intact rats resulted in a comparable decrease in lutropin receptors with a transient increase in testicular responsiveness. Rats receiving twice-daily injections of 15 microgram lutropin for 10 days exhibited a 48% decrease in lutropin receptors by day 3 which persisted during the 10-day treatment period, but was accompanied by a progressive increase in testicular responsiveness to lutropin. Hypophysectomy resulted in an 80% loss of receptors and a 72% loss in responsiveness 7 days after surgery. Daily treatment with lutropin initiated immediately following surgery resulted in a further dose-dependent decrease in lutropin receptors and a dose-dependent increase in testicular responsiveness. Loss of lutropin receptors was not due to occupancy of the receptor by exogenous lutropin. These studies demonstrate a dissociation between the negative regulation of lutropin receptors and testicular responsiveness to lutropin. Furthermore, the studies in hypophysectomized rats indicate that lutropin is the only hormone essential for maintenance of steroidogenesis and that this is independent of lutropin receptor concentration.", "contents": "Dissociation of lutropin-induced loss of testicular lutropin receptors and lutropin-induced desensitization of testosterone synthesis. The relationship between changes in testicular lutropin receptors, as measured by specific binding of 125I-labeled human chorionic gonadotropin, and testosterone synthesis in response to lutropin (testicular responsiveness) was studied in intact and hypophysectomized rats. Administration of a single 200-microgram dose of ovine lutropin to intact rats results at 3 days in a 58% decrease in lutropin receptors associated with a parallel decrease in testicular responsiveness. A single 30-microgram dose of lutropin to intact rats resulted in a comparable decrease in lutropin receptors with a transient increase in testicular responsiveness. Rats receiving twice-daily injections of 15 microgram lutropin for 10 days exhibited a 48% decrease in lutropin receptors by day 3 which persisted during the 10-day treatment period, but was accompanied by a progressive increase in testicular responsiveness to lutropin. Hypophysectomy resulted in an 80% loss of receptors and a 72% loss in responsiveness 7 days after surgery. Daily treatment with lutropin initiated immediately following surgery resulted in a further dose-dependent decrease in lutropin receptors and a dose-dependent increase in testicular responsiveness. Loss of lutropin receptors was not due to occupancy of the receptor by exogenous lutropin. These studies demonstrate a dissociation between the negative regulation of lutropin receptors and testicular responsiveness to lutropin. Furthermore, the studies in hypophysectomized rats indicate that lutropin is the only hormone essential for maintenance of steroidogenesis and that this is independent of lutropin receptor concentration."}
{"id": "PMID:207356", "title": "Mercury complexes of thionicotinamide adenine dinucleotide.", "content": "One-to-one mercury complexes of thionicotinamide adenine dinucleotide (TNAD+) were prepared by using HgSO4 and Hg(CH3 COO-)2. Optical absorption spectroscopy indicated that the mercury probably binds to the TNAD+ through the thio-keto group on the pyridine ring. X-ray diffraction patterns of crystals of mitochondrial malate dehydrogenase soaked in solution containing TNAD+ . mercury complex indicated binding and the X-ray intensity differences are different from mercurials alone.", "contents": "Mercury complexes of thionicotinamide adenine dinucleotide. One-to-one mercury complexes of thionicotinamide adenine dinucleotide (TNAD+) were prepared by using HgSO4 and Hg(CH3 COO-)2. Optical absorption spectroscopy indicated that the mercury probably binds to the TNAD+ through the thio-keto group on the pyridine ring. X-ray diffraction patterns of crystals of mitochondrial malate dehydrogenase soaked in solution containing TNAD+ . mercury complex indicated binding and the X-ray intensity differences are different from mercurials alone."}
{"id": "PMID:207357", "title": "[Kinetic characteristics of thiamine diphosphate biosynthesis by thiamine pyrophosphokinase from rat liver].", "content": "The kinetic analysis of bisubstrate enzymatic reaction catalysed by electrophoretically homogenous thiamine pyrophosphokinase (EC 2.7.6.2), isolated from rat liver has been carried out. Kinetic studies of the initial rates in the absence of the products and inhibition by the reaction products as well as the data from the equilibrium dialysis suggest that the reaction proceeds through the formation of a ternary enzyme-substrate complex. The combination with substrates and release of the products appears to be highly ordered. A possible scheme of the reaction mechanism is discussed.", "contents": "[Kinetic characteristics of thiamine diphosphate biosynthesis by thiamine pyrophosphokinase from rat liver]. The kinetic analysis of bisubstrate enzymatic reaction catalysed by electrophoretically homogenous thiamine pyrophosphokinase (EC 2.7.6.2), isolated from rat liver has been carried out. Kinetic studies of the initial rates in the absence of the products and inhibition by the reaction products as well as the data from the equilibrium dialysis suggest that the reaction proceeds through the formation of a ternary enzyme-substrate complex. The combination with substrates and release of the products appears to be highly ordered. A possible scheme of the reaction mechanism is discussed."}
{"id": "PMID:207358", "title": "[Protein inhibitor of the retinal cyclic nucleotide phosphodiesterase: its localization in the outer segment of a photoreceptor].", "content": "The content of a protein inhibitor of the cyclic nucleotides phosphodiesterase (PDE) in different retinal preparations as well as its distribution in the subfractions of rod outer segments (ROS) was studied. The content of protein inhibitor of PDE in different preparations of the retina was found to correlate with the rhodopsin content. The distribution of this protein over different ROS subfractions appeared to be exactly the same as that of rhodopsin, the content of protein inhibitor of PDE being more than a half of its content in the native ROS. The protein inhibitor of PDE could be easily washed out from the ROS fractions. It is concluded that the cattle protein inhibitor of PDE is localized in ROS, and is absent in the other retinal layers.", "contents": "[Protein inhibitor of the retinal cyclic nucleotide phosphodiesterase: its localization in the outer segment of a photoreceptor]. The content of a protein inhibitor of the cyclic nucleotides phosphodiesterase (PDE) in different retinal preparations as well as its distribution in the subfractions of rod outer segments (ROS) was studied. The content of protein inhibitor of PDE in different preparations of the retina was found to correlate with the rhodopsin content. The distribution of this protein over different ROS subfractions appeared to be exactly the same as that of rhodopsin, the content of protein inhibitor of PDE being more than a half of its content in the native ROS. The protein inhibitor of PDE could be easily washed out from the ROS fractions. It is concluded that the cattle protein inhibitor of PDE is localized in ROS, and is absent in the other retinal layers."}
{"id": "PMID:207359", "title": "[Protein phosphorylation in normal and neoplastic hepatocytes].", "content": "Partially purified preparations of protein kinase were isolated from the cytoplasm and nuclei of rat liver and hepatoma 27 and characterized in terms of their substrate specificity. The protein kinases from normal liver and hepatoma revealed some differences in phosphorylating protein substrates. Hepatoma protein kinases were found to phosphorylate arginine-rich histones (H3, H4); differences in phosphorylation of histone H1 were revealed. Hepatoma protein kinases phosphorylated the C-terminal fragment of histone H1, whereas normal liver protein kinases produced no such effect. It was assumed that the phosphorylation of histone H1 in rapidly dividing and resting cells is operated through different channels.", "contents": "[Protein phosphorylation in normal and neoplastic hepatocytes]. Partially purified preparations of protein kinase were isolated from the cytoplasm and nuclei of rat liver and hepatoma 27 and characterized in terms of their substrate specificity. The protein kinases from normal liver and hepatoma revealed some differences in phosphorylating protein substrates. Hepatoma protein kinases were found to phosphorylate arginine-rich histones (H3, H4); differences in phosphorylation of histone H1 were revealed. Hepatoma protein kinases phosphorylated the C-terminal fragment of histone H1, whereas normal liver protein kinases produced no such effect. It was assumed that the phosphorylation of histone H1 in rapidly dividing and resting cells is operated through different channels."}
{"id": "PMID:207360", "title": "[Study of insulin receptors on liver and hepatoma cell plasma membranes].", "content": "Plasma membranes (PM) of helathy rats as well as those hepatomas and PM of tumor-bearing rats were found (radioreceptor assay) to have apparently two groups of receptors for insulin with a high and low affinity for the hormone respectively and different insulin-binding capacities. Kass values of the receptors with a high affinity for insulin are drastically decreased in the PM of ascites Zajdela hepatoma (AZH) and of solid hepatoma 27 (SH-27) as well as in the liver of SH-27-bearing animals, but not in the liver of the AZH-bearing rats. Kass values of the receptors with a low affinity for insulin in the PM of AZH and in those of the liver of AZH-bearing rats appear nearly normal. In contrary, above Kass the receptors in the PM of SH-27 and SH-27-bearing animals are significantly decreased. The insulin-binding capacity of the receptors with a high affinity for the hormone in the PM of SH-27, AZH and the liver of both tumor-bearing rats is shown to be significantly higher than that in the PM of normal animals. The same property of the receptors with a low is affinity in the PM of the hepatomas and theliver of their hosts is also increased, especially in the PM of SH-27 and of the liver of SH-27-carring rats.", "contents": "[Study of insulin receptors on liver and hepatoma cell plasma membranes]. Plasma membranes (PM) of helathy rats as well as those hepatomas and PM of tumor-bearing rats were found (radioreceptor assay) to have apparently two groups of receptors for insulin with a high and low affinity for the hormone respectively and different insulin-binding capacities. Kass values of the receptors with a high affinity for insulin are drastically decreased in the PM of ascites Zajdela hepatoma (AZH) and of solid hepatoma 27 (SH-27) as well as in the liver of SH-27-bearing animals, but not in the liver of the AZH-bearing rats. Kass values of the receptors with a low affinity for insulin in the PM of AZH and in those of the liver of AZH-bearing rats appear nearly normal. In contrary, above Kass the receptors in the PM of SH-27 and SH-27-bearing animals are significantly decreased. The insulin-binding capacity of the receptors with a high affinity for the hormone in the PM of SH-27, AZH and the liver of both tumor-bearing rats is shown to be significantly higher than that in the PM of normal animals. The same property of the receptors with a low is affinity in the PM of the hepatomas and theliver of their hosts is also increased, especially in the PM of SH-27 and of the liver of SH-27-carring rats."}
{"id": "PMID:207361", "title": "[Redox potentials of some metalloproteins].", "content": "The standard redox potentials of soluble cytochromes c isolated from the green alga Chlorella and the blue-green algae Spirulina and Aphanezomenon were determined by potentiometric titration and found to be equal to +380 mB, +330 mB and +357 AB, respectively. The standard redox potentials of plastocyanin preparations from Pisum sativum and Atriplex leaves were also determined and found close to those of soluble cytochromes c, i. e. +395 mB and +375 mB, respectively. The metalloproteins studied were shown to belong to monoelectron carriers operating at the donor sites of photosystem I.", "contents": "[Redox potentials of some metalloproteins]. The standard redox potentials of soluble cytochromes c isolated from the green alga Chlorella and the blue-green algae Spirulina and Aphanezomenon were determined by potentiometric titration and found to be equal to +380 mB, +330 mB and +357 AB, respectively. The standard redox potentials of plastocyanin preparations from Pisum sativum and Atriplex leaves were also determined and found close to those of soluble cytochromes c, i. e. +395 mB and +375 mB, respectively. The metalloproteins studied were shown to belong to monoelectron carriers operating at the donor sites of photosystem I."}
{"id": "PMID:207362", "title": "[Comparative study of B890 pigment-lipoprotein complexes from sulfur (Chromatium minutissimum) and non-sulfur (Rhodopseudomonas palustris) purple photosynthesizing bacteria].", "content": "Pigment-lipoprotein B890 complexes containing reaction center and \"light-focusing\" bacteriochlorophyll a were isolated from photosynthetic membranes of sulfur (Chromatium minutissimum) and non-sulfur (Rhodopseudomonas palustris) purple bacteria after the treatment with Triton X-100. The molecular weights of complexes were evaluated using several methods (200 000-300 000). By means of electron microscopy the sizes of complexes were found to be about 80 A. On the air-water interface hexagonal packing of complexes was observed. The chemical compositions of complexes are very similar except bacteriochlorophyll a whose specific content is somewhat higher in Chromatium minutissimum. The protein composition of complexes was studied and the molecular weights of proteins were estimated by SDS-gel electrophoresis. The results obtained show significant similarities in molecular organization of B890 complexes isolated from sulfur (Chromatium minutissimum) and non-sulfur (Rhodopseudomonas palustris) purple bacteria.", "contents": "[Comparative study of B890 pigment-lipoprotein complexes from sulfur (Chromatium minutissimum) and non-sulfur (Rhodopseudomonas palustris) purple photosynthesizing bacteria]. Pigment-lipoprotein B890 complexes containing reaction center and \"light-focusing\" bacteriochlorophyll a were isolated from photosynthetic membranes of sulfur (Chromatium minutissimum) and non-sulfur (Rhodopseudomonas palustris) purple bacteria after the treatment with Triton X-100. The molecular weights of complexes were evaluated using several methods (200 000-300 000). By means of electron microscopy the sizes of complexes were found to be about 80 A. On the air-water interface hexagonal packing of complexes was observed. The chemical compositions of complexes are very similar except bacteriochlorophyll a whose specific content is somewhat higher in Chromatium minutissimum. The protein composition of complexes was studied and the molecular weights of proteins were estimated by SDS-gel electrophoresis. The results obtained show significant similarities in molecular organization of B890 complexes isolated from sulfur (Chromatium minutissimum) and non-sulfur (Rhodopseudomonas palustris) purple bacteria."}
{"id": "PMID:207363", "title": "[Effect of growth conditions on the activity of the enzymes of cyclic 3':5'-AMP synthesis and decay in phototrophic bacteria].", "content": "Activity, ratio and summary content of cyclic AMP enzymes, adenylate cyclase and phosphodiesterase varied depending on growth conditions of phototrophic bacteria (Rhodospirillum rubrum and Rhodopseudomonas palustris). It suggests, that membrane-bound and soluble enzymes carry different functions. The increase of adenylate cyclase under chaning growth conditions was usually accompanied by the increase of phosphodiesterase. Sharp increase of both enzymes activity was observed when bacteria were growth in aerobic conditions. The activity of both enzymes in chromatophores was 2.8-fold higher when bacteria were grown in the light in anaerobic conditions, than in chromatophores of bacteria grown under stationary aerobic conditions in the light. It is suggested that 3':5' AMP can participate in autotrophic carbon assimilation or in the synthesis of pigments and other components of bacterial photosynthetizing apparatus. Substitution of NH4+ into NO3- and glutamate under the growing of R. rubrum in anaerobic conditions in the light resulted in the increase of the enzymes activities, which is the evidence of possible role of 3':5' AMP in mineral nitrogen uptake and nitrogen fixation. Glutamate concentration of 4 g/l stimulated the enzymes both in vivo and in vitro. The data obtained suggest that 3':5' AMP can carry multiple functions, participating in regulation of a number of metabolic processes in photorophic bacteria.", "contents": "[Effect of growth conditions on the activity of the enzymes of cyclic 3':5'-AMP synthesis and decay in phototrophic bacteria]. Activity, ratio and summary content of cyclic AMP enzymes, adenylate cyclase and phosphodiesterase varied depending on growth conditions of phototrophic bacteria (Rhodospirillum rubrum and Rhodopseudomonas palustris). It suggests, that membrane-bound and soluble enzymes carry different functions. The increase of adenylate cyclase under chaning growth conditions was usually accompanied by the increase of phosphodiesterase. Sharp increase of both enzymes activity was observed when bacteria were growth in aerobic conditions. The activity of both enzymes in chromatophores was 2.8-fold higher when bacteria were grown in the light in anaerobic conditions, than in chromatophores of bacteria grown under stationary aerobic conditions in the light. It is suggested that 3':5' AMP can participate in autotrophic carbon assimilation or in the synthesis of pigments and other components of bacterial photosynthetizing apparatus. Substitution of NH4+ into NO3- and glutamate under the growing of R. rubrum in anaerobic conditions in the light resulted in the increase of the enzymes activities, which is the evidence of possible role of 3':5' AMP in mineral nitrogen uptake and nitrogen fixation. Glutamate concentration of 4 g/l stimulated the enzymes both in vivo and in vitro. The data obtained suggest that 3':5' AMP can carry multiple functions, participating in regulation of a number of metabolic processes in photorophic bacteria."}
{"id": "PMID:207364", "title": "Urinary content of 3',5'-adenosine monophosphate (cAMP) and creatinine in full-term and premature infants.", "content": "Cyclic 3',5'-monophosphate (c-AMP) and creatinine were measured in full-term and premature infants. In normals, values for c-AMP were highest on days 1 and 2 (1.3-1.5 nmol/ml) and decreased thereafter. In prematures the c-AMP values were significantly lower than in the full-term infants. There was a rough correlation with birth weight. Creatinine values were closely reflected by the c-AMP levels. Changes found in neonatal jaundice, hypocalcaemia, respiratory distress syndrome, and anoxia could be attributed to prematurity. No diurnal variation in c-AMP values was found.", "contents": "Urinary content of 3',5'-adenosine monophosphate (cAMP) and creatinine in full-term and premature infants. Cyclic 3',5'-monophosphate (c-AMP) and creatinine were measured in full-term and premature infants. In normals, values for c-AMP were highest on days 1 and 2 (1.3-1.5 nmol/ml) and decreased thereafter. In prematures the c-AMP values were significantly lower than in the full-term infants. There was a rough correlation with birth weight. Creatinine values were closely reflected by the c-AMP levels. Changes found in neonatal jaundice, hypocalcaemia, respiratory distress syndrome, and anoxia could be attributed to prematurity. No diurnal variation in c-AMP values was found."}
{"id": "PMID:207365", "title": "Calcium and 25-hydroxyvitamin D3 binding proteins in human placenta.", "content": "The placental translocation of calcium is a well-known process, but the underlying mechanisms remain unknown. Placental cytoplasmic proteins capable of binding calcium and the active metabolites of vitamin D3 were sought in these studies. Cytosol from full-term human placenta was prepared by ultracentrifugation of homogenates and tested for binding. Partial purification by column chromatography revealed the presence of two discrete proteins which bound specifically 45Ca and 3H-25-hydroxyvitamin D3 and having approximate molecular weights of 12,000 and 67,000, respectively. These placental proteins may be intermediaries in the process of placental calcium translocation.", "contents": "Calcium and 25-hydroxyvitamin D3 binding proteins in human placenta. The placental translocation of calcium is a well-known process, but the underlying mechanisms remain unknown. Placental cytoplasmic proteins capable of binding calcium and the active metabolites of vitamin D3 were sought in these studies. Cytosol from full-term human placenta was prepared by ultracentrifugation of homogenates and tested for binding. Partial purification by column chromatography revealed the presence of two discrete proteins which bound specifically 45Ca and 3H-25-hydroxyvitamin D3 and having approximate molecular weights of 12,000 and 67,000, respectively. These placental proteins may be intermediaries in the process of placental calcium translocation."}
{"id": "PMID:207370", "title": "[Change in the concentration of nucleic acids and cAMP in neurogenic dystrophies of the stomach].", "content": "There proved to be a reduction of the RNA content in the tissue of the rat stomach in its dystrophic affection induced by traumatization of the duodenum, this pointing to the reconstruction of the cell genetic apparatus under conditions of extreme stimulation. Under the same experimental conditions there was a pronounced decrease of the cAMP level in the gastric mucosa of rabbits. The significance of the changes in the mechanism of the development of destructive and metabolic disturbances in the neurogenic dystrophic affections induced by extreme stimulation is discussed.", "contents": "[Change in the concentration of nucleic acids and cAMP in neurogenic dystrophies of the stomach]. There proved to be a reduction of the RNA content in the tissue of the rat stomach in its dystrophic affection induced by traumatization of the duodenum, this pointing to the reconstruction of the cell genetic apparatus under conditions of extreme stimulation. Under the same experimental conditions there was a pronounced decrease of the cAMP level in the gastric mucosa of rabbits. The significance of the changes in the mechanism of the development of destructive and metabolic disturbances in the neurogenic dystrophic affections induced by extreme stimulation is discussed."}
{"id": "PMID:207371", "title": "[Effect of heparin on the activity of liver microsome oxidative enzyme systems in healthy rats and rats with experimental glomerulonephritis].", "content": "In experiments on mongrel rats it was found that heparin in doses of 2, 5, and 10 mg/kg had an inducing effect on the oxidative systems of hepatic microsomes: hexenal test period was shortened, cytochrome P450 content increased, relative liver weight rose; the activity of histochemically-detectable NAD-enzymes of hepatocytes became greater. Heparin was capable of considerable (2-3-fold) stimulation of antitoxic activity of the liver reduced in experimental glomerulonephritis. The effect of heparin on the antitoxic function of the liver did not correlate with its effect, on the blood coagulation system.", "contents": "[Effect of heparin on the activity of liver microsome oxidative enzyme systems in healthy rats and rats with experimental glomerulonephritis]. In experiments on mongrel rats it was found that heparin in doses of 2, 5, and 10 mg/kg had an inducing effect on the oxidative systems of hepatic microsomes: hexenal test period was shortened, cytochrome P450 content increased, relative liver weight rose; the activity of histochemically-detectable NAD-enzymes of hepatocytes became greater. Heparin was capable of considerable (2-3-fold) stimulation of antitoxic activity of the liver reduced in experimental glomerulonephritis. The effect of heparin on the antitoxic function of the liver did not correlate with its effect, on the blood coagulation system."}
{"id": "PMID:207372", "title": "[Activity of gluconeogenetic enzymes of rat kidney cortex during acute hypoxia].", "content": "The activities of gluconeogenic enzymes of the rat kidney cortex was studied after exposure to lowered atmospheric pressure (200 mm Hg) for 3 hours. The hypoxic stress was found to cause an increase in the activities of phosphoenolpyruvate carboxykinase and alanine aminotransferase, but failed to affect significantly the activities of fructose-1,6-diphosphatase, glucose-6-phosphatase, and aspartate aminotranspherase. The ratio of glucose-6-phosphatase/hexokinase activities was increased under these conditions.", "contents": "[Activity of gluconeogenetic enzymes of rat kidney cortex during acute hypoxia]. The activities of gluconeogenic enzymes of the rat kidney cortex was studied after exposure to lowered atmospheric pressure (200 mm Hg) for 3 hours. The hypoxic stress was found to cause an increase in the activities of phosphoenolpyruvate carboxykinase and alanine aminotransferase, but failed to affect significantly the activities of fructose-1,6-diphosphatase, glucose-6-phosphatase, and aspartate aminotranspherase. The ratio of glucose-6-phosphatase/hexokinase activities was increased under these conditions."}
{"id": "PMID:207373", "title": "[Regulatory role of DOPA and components of the cyclic adenosine-3',5'-monophosphate system].", "content": "It was shown on albino mice that when DOPA-3H (20 muCi/mouse) was administered before nonradioactive DOPA (1 mg/mouse) tritium accumulation in the tissue of Harding-Passi's melanoma of these mice proved to increase. Melanoma radioactivity in this experimental group was double that in the tumour tissue of the animals to which DOPA-3H alone was administered. Examination of the adenylate cyclase, phosphodiesterase activity and of the level of cAMP in melanoma of mice 2 hours after DOPA administration (1 mg/mouse) showed accumulation of cAMP and an increase in the phosphodiesterase activity; as to adenylate cyclase activity--it fell. It is suggested that DOPA realizes its effect not only as melanin precursor, but also through the cAMP system, influencing the melanogenesis enzymes activity.", "contents": "[Regulatory role of DOPA and components of the cyclic adenosine-3',5'-monophosphate system]. It was shown on albino mice that when DOPA-3H (20 muCi/mouse) was administered before nonradioactive DOPA (1 mg/mouse) tritium accumulation in the tissue of Harding-Passi's melanoma of these mice proved to increase. Melanoma radioactivity in this experimental group was double that in the tumour tissue of the animals to which DOPA-3H alone was administered. Examination of the adenylate cyclase, phosphodiesterase activity and of the level of cAMP in melanoma of mice 2 hours after DOPA administration (1 mg/mouse) showed accumulation of cAMP and an increase in the phosphodiesterase activity; as to adenylate cyclase activity--it fell. It is suggested that DOPA realizes its effect not only as melanin precursor, but also through the cAMP system, influencing the melanogenesis enzymes activity."}
{"id": "PMID:207374", "title": "[Experimental influenza caused by an incomplete form of the agent].", "content": "Incomplete form of the influenza virus obtained in accordance with Nayak's method was administered intranasally to mice CBA and C57BL. From the lung tissue of the infected mice the causative agent could be isolated for 45 days, and from the other internal organs--the first hours after the infection only. In morphological investigation of the lungs of animals infected with an incomplete form of the influenza virus a prevalence of the proliferative component against the background of inflammatory changes was noted. Three months after the infection limited lymphoid formations consisting of monomorphic cells with hyperchromic nuclei were defined in the lung tissue. Marked proliferation of the alveolar and bronchial epithelium was observed later; considerable anaplasia of the cells was noted in the papillomatous structure of the alveolar and bronchial epithelium. Glomangioma of the mesentery was observed among affections of other internal organs in 18.7% of mice CBA.", "contents": "[Experimental influenza caused by an incomplete form of the agent]. Incomplete form of the influenza virus obtained in accordance with Nayak's method was administered intranasally to mice CBA and C57BL. From the lung tissue of the infected mice the causative agent could be isolated for 45 days, and from the other internal organs--the first hours after the infection only. In morphological investigation of the lungs of animals infected with an incomplete form of the influenza virus a prevalence of the proliferative component against the background of inflammatory changes was noted. Three months after the infection limited lymphoid formations consisting of monomorphic cells with hyperchromic nuclei were defined in the lung tissue. Marked proliferation of the alveolar and bronchial epithelium was observed later; considerable anaplasia of the cells was noted in the papillomatous structure of the alveolar and bronchial epithelium. Glomangioma of the mesentery was observed among affections of other internal organs in 18.7% of mice CBA."}
{"id": "PMID:207375", "title": "[Electron microscopic demonstration of adenylate cyclase in rabbit small intestine enterocytes doubly stimulated by cholera toxin and sodium fluoride].", "content": "Cytochemical investigations showed adenylate cyclase in the rabbit small intestine enterocytes to be activated both with cholera toxin and sodium fluoride. Following double stimulation of adenylate cyclase in the intestinal enterocytes by the mentioned two substances maximal critical levels of cAMP were attained resulting in self-inhibition of adenylate cyclase; in this case only a low adenylate cyclase activity, if any, could be demonstrated by electron microscopy.", "contents": "[Electron microscopic demonstration of adenylate cyclase in rabbit small intestine enterocytes doubly stimulated by cholera toxin and sodium fluoride]. Cytochemical investigations showed adenylate cyclase in the rabbit small intestine enterocytes to be activated both with cholera toxin and sodium fluoride. Following double stimulation of adenylate cyclase in the intestinal enterocytes by the mentioned two substances maximal critical levels of cAMP were attained resulting in self-inhibition of adenylate cyclase; in this case only a low adenylate cyclase activity, if any, could be demonstrated by electron microscopy."}
{"id": "PMID:207376", "title": "[Leukocyte migration inhibition reaction in trophoblastic tumor patients].", "content": "Inhibition of leukocyte migration was studied in 40 patients with trophoblastic tumours under the effect of protein extract from chorionepithelioma. A marked inhibition of leukocyte migration was revealed in patients with signs of active tumour process before and during the treatment. Four patients in whom no inhibition was revealed either before or during the treatment were an exception. In the majority of the patients the inhibition effect was absent against the background of clinical well-being achieved as a result of surgical and chemotherapeutic, or chemotherapeutic treatment alone. Leukocytes of healthy donors failed to respond to the tumour extract in all 24 cases.", "contents": "[Leukocyte migration inhibition reaction in trophoblastic tumor patients]. Inhibition of leukocyte migration was studied in 40 patients with trophoblastic tumours under the effect of protein extract from chorionepithelioma. A marked inhibition of leukocyte migration was revealed in patients with signs of active tumour process before and during the treatment. Four patients in whom no inhibition was revealed either before or during the treatment were an exception. In the majority of the patients the inhibition effect was absent against the background of clinical well-being achieved as a result of surgical and chemotherapeutic, or chemotherapeutic treatment alone. Leukocytes of healthy donors failed to respond to the tumour extract in all 24 cases."}
{"id": "PMID:207377", "title": "Long-term cultivation of plasma cell leukemia cells and autologous lymphoblasts (LCL) in vitro: a comparative study.", "content": "Two long-term cell lines were established in vitro from the peripheral blood of a patient with plasma cell leukemia: one line with plasma cell proliferation, the other with lymphoblastoid cell proliferation (LCL). The 9-month-old plasma cell line showed the typical morphology of plasmoblasts. The cells neither had B- nor T-lymphocyte characterisitics, were EBV negative, and showed aneuploidy with various marker chromosomes, including the 14 q+ marker. The cytogenetic findings indicate a monoclonal proliferation of the plasmacells. No tumor growth in thymusless nude mice could be induced upon intracranial inoculation with these cells. In contrast, the autologous LCL, cultured after addition of exogenous EBV, showed the characteristic markers of lymphoblastoid cells, with the typical morphology of pear- and handmirror-shaped lymphoblasts, growing in clumps. They had C3- and Fc-receptors, surface-Ig, E-rosette-negativity, a diploid karyotype, and EBV dependent macromolecule synthesis. They lymphoblastoid cells produced intracranial tumors in nude mice in 8 out of 8 attempts.", "contents": "Long-term cultivation of plasma cell leukemia cells and autologous lymphoblasts (LCL) in vitro: a comparative study. Two long-term cell lines were established in vitro from the peripheral blood of a patient with plasma cell leukemia: one line with plasma cell proliferation, the other with lymphoblastoid cell proliferation (LCL). The 9-month-old plasma cell line showed the typical morphology of plasmoblasts. The cells neither had B- nor T-lymphocyte characterisitics, were EBV negative, and showed aneuploidy with various marker chromosomes, including the 14 q+ marker. The cytogenetic findings indicate a monoclonal proliferation of the plasmacells. No tumor growth in thymusless nude mice could be induced upon intracranial inoculation with these cells. In contrast, the autologous LCL, cultured after addition of exogenous EBV, showed the characteristic markers of lymphoblastoid cells, with the typical morphology of pear- and handmirror-shaped lymphoblasts, growing in clumps. They had C3- and Fc-receptors, surface-Ig, E-rosette-negativity, a diploid karyotype, and EBV dependent macromolecule synthesis. They lymphoblastoid cells produced intracranial tumors in nude mice in 8 out of 8 attempts."}
{"id": "PMID:207383", "title": "Specific immunity to human papilloma virus (HPV) in patients with genital warts.", "content": "A study of human papilloma virus (HPV) specific cellular and humoral immunity in 30 patients with genital warts is reported. By in vivo testing with purified, inactivated plantar wart virus, a cell-mediated immunity to HPV was determined in 60% of patients. Circulating antibodies, evaluated by immunofluorescence testing, were rare, but these increased after an intradermal test had been carried out, especially in patients with a positive skin test, suggesting a booster effect. No significant difference was found between this group of patients and those having skin warts. Our results showed a specific immune response to HPV in most patients, confirming the role of the viral agent in the induction of genital warts.", "contents": "Specific immunity to human papilloma virus (HPV) in patients with genital warts. A study of human papilloma virus (HPV) specific cellular and humoral immunity in 30 patients with genital warts is reported. By in vivo testing with purified, inactivated plantar wart virus, a cell-mediated immunity to HPV was determined in 60% of patients. Circulating antibodies, evaluated by immunofluorescence testing, were rare, but these increased after an intradermal test had been carried out, especially in patients with a positive skin test, suggesting a booster effect. No significant difference was found between this group of patients and those having skin warts. Our results showed a specific immune response to HPV in most patients, confirming the role of the viral agent in the induction of genital warts."}
{"id": "PMID:207384", "title": "Strychinine binding associated with synaptic glycine receptors in rat spinal cord membranes: ionic influences.", "content": "Ammonium salts of some anions decrease the potency of glycine in inhibiting (3H)strychnine binding associated with synaptic glycine receptors. A correspondence exists between the ability of the ammonium salts of anions to increase the IC50 of glycine in inhibiting the (3H) strychnine binding, their capacity to reduce the (3H) strychnine binding itself, and their capacity to reverse inhibitory postsynaptic potentials. The decrease of (3H)strychnine binding in the presence of chloride is abolished by sodium, while the decrease of the potency of glycine in inhibiting (3H)strychnine is not. Binding of (3H)strychnine is influenced by monovalent cations in a biphasic fashion. Concentrations of Li+, K+, and Na+ up to 150mM decrease (3H)strychnine binding, while higher concentrations of the cations increase (3H)strychnine binding. Inhibition by glycine of (3H)strychnine binding is enhanced by low concentrations of these cations.", "contents": "Strychinine binding associated with synaptic glycine receptors in rat spinal cord membranes: ionic influences. Ammonium salts of some anions decrease the potency of glycine in inhibiting (3H)strychnine binding associated with synaptic glycine receptors. A correspondence exists between the ability of the ammonium salts of anions to increase the IC50 of glycine in inhibiting the (3H) strychnine binding, their capacity to reduce the (3H) strychnine binding itself, and their capacity to reverse inhibitory postsynaptic potentials. The decrease of (3H)strychnine binding in the presence of chloride is abolished by sodium, while the decrease of the potency of glycine in inhibiting (3H)strychnine is not. Binding of (3H)strychnine is influenced by monovalent cations in a biphasic fashion. Concentrations of Li+, K+, and Na+ up to 150mM decrease (3H)strychnine binding, while higher concentrations of the cations increase (3H)strychnine binding. Inhibition by glycine of (3H)strychnine binding is enhanced by low concentrations of these cations."}
{"id": "PMID:207385", "title": "An ultrastructural study into the effects of pentobarbitone on synaptic organization.", "content": "A series of adult male rats was analyzed to test the effects of varying doses of pentobarbitone sodium on the ultrastructure of synapses in the molecular layer of the parietal cortex. The rats were divided into the following categories: unanaesthetized stunned, unanaesthetized cannulated and those subjected to 40, 80, 160, 300, or 400 mg/kg pentobarbitone. All material was examined both qualitatively and quantitatively after aldehyde-OsO4 or ethanolic phosphotungstic acid (E-PTA) treatment. The principal qualitative observations were: the preponderance in the unanaesthetized stunned and 160-400 mg/kg material of a variety of intraterminal profiles including synaptic vesicles, mitochondria, coated vesicles, tubular profiles, vacuoles, cisterns and double membrane profiles; the presence of exocytotic sites along the presynaptic membrane in the unanaesthetized stunned and cannulated material; the presence of endocytotic sites over the limiting membrane of the terminal away from the cleft in the unanaesthetized stunned and 160-400 mg/kg material; the prominence of the presynaptic network in the unanaesthetized and 40 mg/kg E-PTA material; discontinuity of the cleft material in the 40-160 mg/kg material. Findings to emerge from the quantitative aspect of the study show that pentobarbitone influences synaptic curvature, with a marked increase in curvature negativity over the 0-80 mg/kg dose range and a decrease in negativity at higher dose levels. The increase in curvature negativity is accompanied by an increase in synaptic length and dense projection numbers, with a consonant increase in the perimeter and area of the presynaptic terminal. Reversal of the negativity trend at higher dose levels is parallelled  by reversal of these accompanying trends. Both sets of findings can be accounted for by membrane recycling within the terminal, supporting a membrane redistribution hypothesis.", "contents": "An ultrastructural study into the effects of pentobarbitone on synaptic organization. A series of adult male rats was analyzed to test the effects of varying doses of pentobarbitone sodium on the ultrastructure of synapses in the molecular layer of the parietal cortex. The rats were divided into the following categories: unanaesthetized stunned, unanaesthetized cannulated and those subjected to 40, 80, 160, 300, or 400 mg/kg pentobarbitone. All material was examined both qualitatively and quantitatively after aldehyde-OsO4 or ethanolic phosphotungstic acid (E-PTA) treatment. The principal qualitative observations were: the preponderance in the unanaesthetized stunned and 160-400 mg/kg material of a variety of intraterminal profiles including synaptic vesicles, mitochondria, coated vesicles, tubular profiles, vacuoles, cisterns and double membrane profiles; the presence of exocytotic sites along the presynaptic membrane in the unanaesthetized stunned and cannulated material; the presence of endocytotic sites over the limiting membrane of the terminal away from the cleft in the unanaesthetized stunned and 160-400 mg/kg material; the prominence of the presynaptic network in the unanaesthetized and 40 mg/kg E-PTA material; discontinuity of the cleft material in the 40-160 mg/kg material. Findings to emerge from the quantitative aspect of the study show that pentobarbitone influences synaptic curvature, with a marked increase in curvature negativity over the 0-80 mg/kg dose range and a decrease in negativity at higher dose levels. The increase in curvature negativity is accompanied by an increase in synaptic length and dense projection numbers, with a consonant increase in the perimeter and area of the presynaptic terminal. Reversal of the negativity trend at higher dose levels is parallelled  by reversal of these accompanying trends. Both sets of findings can be accounted for by membrane recycling within the terminal, supporting a membrane redistribution hypothesis."}
{"id": "PMID:207386", "title": "Muscimol binding in rat brain: association with synaptic GABA receptors.", "content": "[3H]Muscimol binding to crude synaptic membrane fractions of the rat central nervous is saturable with a high affinity dissociation constant of 2.2 nM. The regional distribution of this binding in rat brain and the effects of freezing, sodium and Triton X-100 are similar to those previously reported for [3H]GABA binding to the the synaptic GABA receptor site. Also, the substrate specificity of [3H]muscimol binding is identifical to that observed for the GABA receptor. Thus, [3H]muscimol is displaced, stereospecifically, only by those drugs and amino acids which are known to neurophysiologically interact with the synaptic GABA receptor but is unaffected by agents which activate or inhibit other neurotransmitter receptors. This suggests that the behavioral effects observed after the systemic administration of muscimol are probably the result of GABA receptor activation.", "contents": "Muscimol binding in rat brain: association with synaptic GABA receptors. [3H]Muscimol binding to crude synaptic membrane fractions of the rat central nervous is saturable with a high affinity dissociation constant of 2.2 nM. The regional distribution of this binding in rat brain and the effects of freezing, sodium and Triton X-100 are similar to those previously reported for [3H]GABA binding to the the synaptic GABA receptor site. Also, the substrate specificity of [3H]muscimol binding is identifical to that observed for the GABA receptor. Thus, [3H]muscimol is displaced, stereospecifically, only by those drugs and amino acids which are known to neurophysiologically interact with the synaptic GABA receptor but is unaffected by agents which activate or inhibit other neurotransmitter receptors. This suggests that the behavioral effects observed after the systemic administration of muscimol are probably the result of GABA receptor activation."}
{"id": "PMID:207388", "title": "Small mode miniature end plate potentials are increased and evoked in fatigued preparations and in high Mg2+ saline.", "content": "Amplitude histograms of miniature end-plate potentials (MEPPs) from small sartorius fibers (6-20 micron diam.) of very small frogs were found to have multiple peaks. All MEPPs had the same time characteristics which demonstrates that they arose at the same junction. The amplitude of the smallest mode (s-MEPPs) was one-seventh that of the major mode (m-MEPPs), and in the unstressed preparation s-MEPPs composed only a few per cent of the total. After repetitive nerve stimulation (1 min at 20 Hz) the percentage of s-MEPPs was initially increased. Successive periods of stimulation gradually reduced the end-plate potential (EPP) (above 90% failures) to the same size as s-MEPPs. A 12.5 MM Mg2+ and half normal Ca2+ saline was also found to increase the percentage of s-MEPPs and reduce EPPs so that profiles of EPP amplitude histograms showed a class of small EPPs the same size as s-MEPPs. The data demonstrate that quanta the size of s-MEPPs were released with nerve stimulation in both the Mg2+ blocked and fatigued preparation.", "contents": "Small mode miniature end plate potentials are increased and evoked in fatigued preparations and in high Mg2+ saline. Amplitude histograms of miniature end-plate potentials (MEPPs) from small sartorius fibers (6-20 micron diam.) of very small frogs were found to have multiple peaks. All MEPPs had the same time characteristics which demonstrates that they arose at the same junction. The amplitude of the smallest mode (s-MEPPs) was one-seventh that of the major mode (m-MEPPs), and in the unstressed preparation s-MEPPs composed only a few per cent of the total. After repetitive nerve stimulation (1 min at 20 Hz) the percentage of s-MEPPs was initially increased. Successive periods of stimulation gradually reduced the end-plate potential (EPP) (above 90% failures) to the same size as s-MEPPs. A 12.5 MM Mg2+ and half normal Ca2+ saline was also found to increase the percentage of s-MEPPs and reduce EPPs so that profiles of EPP amplitude histograms showed a class of small EPPs the same size as s-MEPPs. The data demonstrate that quanta the size of s-MEPPs were released with nerve stimulation in both the Mg2+ blocked and fatigued preparation."}
{"id": "PMID:207389", "title": "Interneurons of sympathetic ganglia: divergent cyclic AMP responses and morphology in cat and cow.", "content": "The biochemical properties of the small, intensely fluorescent (SIF) cells of bovine and feline superior cervical ganglia were determined by studying the cyclic AMP responses to incubation in vitro with adrenergic agonists: the morphological properties were studied by fluorescence histochemistry and electron microscopy. Incubation with 50 micron dopamine elicited cyclic AMP levels 524% of control values in the bovine ganglion, but only 152% in the feline ganglion (a value which is not statistically significant). Incubation with 50 micron isoproterenol produced an increase of 356% of control values in the cow, but no increase in the cat. SIF cells were classified into two types by fluorescence histochemistry. The bovine ganglion contained 23.7% Type I (solitary) SIF cells, and 76.3% Type II (clustered) cells, whereas the feline ganglion contained 99.5% Type II cells. Thus the feline ganglion lacks both Type I SIF cells and a dopamine receptor-adenylate cyclase complex. On the basis of biochemical and morphological evidence, we hypothesize that the Type I SIF cell is an interneuron, and infer that the lack of a response to dopamine stimulation in the feline ganglion is caused by a scarcity of interneurons in this species.", "contents": "Interneurons of sympathetic ganglia: divergent cyclic AMP responses and morphology in cat and cow. The biochemical properties of the small, intensely fluorescent (SIF) cells of bovine and feline superior cervical ganglia were determined by studying the cyclic AMP responses to incubation in vitro with adrenergic agonists: the morphological properties were studied by fluorescence histochemistry and electron microscopy. Incubation with 50 micron dopamine elicited cyclic AMP levels 524% of control values in the bovine ganglion, but only 152% in the feline ganglion (a value which is not statistically significant). Incubation with 50 micron isoproterenol produced an increase of 356% of control values in the cow, but no increase in the cat. SIF cells were classified into two types by fluorescence histochemistry. The bovine ganglion contained 23.7% Type I (solitary) SIF cells, and 76.3% Type II (clustered) cells, whereas the feline ganglion contained 99.5% Type II cells. Thus the feline ganglion lacks both Type I SIF cells and a dopamine receptor-adenylate cyclase complex. On the basis of biochemical and morphological evidence, we hypothesize that the Type I SIF cell is an interneuron, and infer that the lack of a response to dopamine stimulation in the feline ganglion is caused by a scarcity of interneurons in this species."}
{"id": "PMID:207394", "title": "Angiotensin receptive neurones in the subfornical organ. Structure-activity relations.", "content": "A microiontophoretic study was performed of the actions of angiotensin II and angiotensin fragments on neurones of the subfornical organ (SFO). Adult cats were anaesthetized and the SFO exposed for penetration by a multibarrelled micropipette. We found that angiotensin II-[2--8]-heptapeptide shows a significantly higher stimulation of firing rate compared to angiotensin II. Angiotensin II-[5--8]-tetrapeptide still produced an excitatory action on a single units. Both the action of the heptapeptide and the tetrapeptide were blocked by [sar1, Ala8]-angiotensin II (P 113). In contrast, angiotensin II-[6--8]-tripeptide failed to enhance the firing rate of the same neurones. Our data indicate that angiotensin II and some shorter chain peptide fragments can directly affect neurones of the SFO. The study may give new insight in structure-activity relations for angiotensin II. The results support the hypothesis that the subfornical organ is a receptor site which is available to this peptide.", "contents": "Angiotensin receptive neurones in the subfornical organ. Structure-activity relations. A microiontophoretic study was performed of the actions of angiotensin II and angiotensin fragments on neurones of the subfornical organ (SFO). Adult cats were anaesthetized and the SFO exposed for penetration by a multibarrelled micropipette. We found that angiotensin II-[2--8]-heptapeptide shows a significantly higher stimulation of firing rate compared to angiotensin II. Angiotensin II-[5--8]-tetrapeptide still produced an excitatory action on a single units. Both the action of the heptapeptide and the tetrapeptide were blocked by [sar1, Ala8]-angiotensin II (P 113). In contrast, angiotensin II-[6--8]-tripeptide failed to enhance the firing rate of the same neurones. Our data indicate that angiotensin II and some shorter chain peptide fragments can directly affect neurones of the SFO. The study may give new insight in structure-activity relations for angiotensin II. The results support the hypothesis that the subfornical organ is a receptor site which is available to this peptide."}
{"id": "PMID:207395", "title": "Norepinephrine attenuation of amnesia produced by diethyldithiocarbamate.", "content": "Rats given 680 mg/kh diethyldithiocarbamate, approximately one half hour before training in an inhibitory avoidance task, had impaired retention performance when tested one week after training. Intracerebroventricular or subcutaneous injections of norepinephrine administered shortly after training attenuated the disruptive effects of DDC on retention performance. The effect depended upon the footshock intensity used during training. NE(0.01 microgram) administered centrally attenuated the DDC induced retention deficit when animals were trained with a high (2 mA) but not a low footshock (0.5 mA). The effect of peripherally administered NE also varied with intensity of footshock. The lowest dose of subcutaneously administered NE (5 microgram/kg) was effective in attenuating DDC induced retention deficits only when animals were trained with higher footshock. Higher doses of NE (50 microgram/kg, 500 microgram/kg) were more effective when animals were trained with lower footshock.", "contents": "Norepinephrine attenuation of amnesia produced by diethyldithiocarbamate. Rats given 680 mg/kh diethyldithiocarbamate, approximately one half hour before training in an inhibitory avoidance task, had impaired retention performance when tested one week after training. Intracerebroventricular or subcutaneous injections of norepinephrine administered shortly after training attenuated the disruptive effects of DDC on retention performance. The effect depended upon the footshock intensity used during training. NE(0.01 microgram) administered centrally attenuated the DDC induced retention deficit when animals were trained with a high (2 mA) but not a low footshock (0.5 mA). The effect of peripherally administered NE also varied with intensity of footshock. The lowest dose of subcutaneously administered NE (5 microgram/kg) was effective in attenuating DDC induced retention deficits only when animals were trained with higher footshock. Higher doses of NE (50 microgram/kg, 500 microgram/kg) were more effective when animals were trained with lower footshock."}
{"id": "PMID:207399", "title": "[Influence of conditions of the acclimatization to cold on the thermogenesis without shivering in rats].", "content": "As indicated by a theophylline administration previously to a norepinephrine infusion, the nonshivering thermogenesis does not seem to be mediated by the cyclic AMP system in constant cold acclimated rats, in opposite to rats acclimated to discontinuous cold. However, in that last thermal condition, the cyclic AMP mediation was not observed in the brown adipose tissue and in the liver.", "contents": "[Influence of conditions of the acclimatization to cold on the thermogenesis without shivering in rats]. As indicated by a theophylline administration previously to a norepinephrine infusion, the nonshivering thermogenesis does not seem to be mediated by the cyclic AMP system in constant cold acclimated rats, in opposite to rats acclimated to discontinuous cold. However, in that last thermal condition, the cyclic AMP mediation was not observed in the brown adipose tissue and in the liver."}
{"id": "PMID:207402", "title": "The dependence of Escherichia coli asparaginase II formation on cyclic AMP and cyclic AMP receptor protein.", "content": "The amount of asparaginase II in an Escherichia coli wild-type strain (cya+, crp+) markedly increased upon a shift from aerobic to anaerobic growth. However, no such increase occurred in a mutant (cya) lacking cyclic AMP synthesis unless supplemented with exogenous cyclic AMP. Since a mutant (crp) deficient in cyclic AMP receptor protein also did not support the anaerobic formation of this enzyme, it is concluded that the formation of E. coli asparaginase II depends on both cyclic AMP and cyclic AMP receptor protein.", "contents": "The dependence of Escherichia coli asparaginase II formation on cyclic AMP and cyclic AMP receptor protein. The amount of asparaginase II in an Escherichia coli wild-type strain (cya+, crp+) markedly increased upon a shift from aerobic to anaerobic growth. However, no such increase occurred in a mutant (cya) lacking cyclic AMP synthesis unless supplemented with exogenous cyclic AMP. Since a mutant (crp) deficient in cyclic AMP receptor protein also did not support the anaerobic formation of this enzyme, it is concluded that the formation of E. coli asparaginase II depends on both cyclic AMP and cyclic AMP receptor protein."}
{"id": "PMID:207403", "title": "Efficacy of laboratory tests for the detection of enterotoxigenic Clostridium perfringens.", "content": "Nineteen Clostridium perfringens strains with positive erythemal and ligated intestinal loop reactions, and 22 strains with negative reactions, originating from food-poisoning cases, were tested comparatively using the fluorescent antibody (FA), reversed passive hemagglutination (RPHA), and immunodiffusion (ID) tests. All the biologically positive strains were detected by the three immunological tests used. The FA test detected five additional strains among the biologically negative group which did not react in RPHA or ID tests. Sporulating culture supernatant fluids, after 13 to 17h of growth, were satisfactory for testing for the presence of enterotoxin by the RPHA and ID tests. The FA test was used on cell smears.", "contents": "Efficacy of laboratory tests for the detection of enterotoxigenic Clostridium perfringens. Nineteen Clostridium perfringens strains with positive erythemal and ligated intestinal loop reactions, and 22 strains with negative reactions, originating from food-poisoning cases, were tested comparatively using the fluorescent antibody (FA), reversed passive hemagglutination (RPHA), and immunodiffusion (ID) tests. All the biologically positive strains were detected by the three immunological tests used. The FA test detected five additional strains among the biologically negative group which did not react in RPHA or ID tests. Sporulating culture supernatant fluids, after 13 to 17h of growth, were satisfactory for testing for the presence of enterotoxin by the RPHA and ID tests. The FA test was used on cell smears."}
{"id": "PMID:207404", "title": "The lipoprotein lipase system: new understandings.", "content": "Hypertriglyceridemia, a risk factor for premature atherosclerosis, may result from decreased use of plasma triglycerides by tissues. The removal of triglycerides is mediated by the enzyme lipoprotein lipase (LPL). Heparin releases LPL from tissues and post-heparin plasma lipolytic activity (PHLA) has been extensively used to elucidate  the mechanism of hypertriglyceridemia in various diseases. There is evidence to show that postheparin plasma contains enzymes other than LPL. Hence data on total PHLA are difficult to interpret. Availability of assays for the LPL component of PHLA has clarified equivocal findings in certain hypertriglyceridemic states. However, the LPL component is also heterogeneous. The LPL \"isoenzymes\" from various extrahepatic tissues behave differently under various metabolic conditions. Therefore, to understand properly the LPL system it is necessary to study the specific tissue LPL. Furthermore, the serum activator for LPL is now characterized. Its importance is evidenced by the recent discovery of a hypertriglyceridemic patient deficient in this apoprotein.", "contents": "The lipoprotein lipase system: new understandings. Hypertriglyceridemia, a risk factor for premature atherosclerosis, may result from decreased use of plasma triglycerides by tissues. The removal of triglycerides is mediated by the enzyme lipoprotein lipase (LPL). Heparin releases LPL from tissues and post-heparin plasma lipolytic activity (PHLA) has been extensively used to elucidate  the mechanism of hypertriglyceridemia in various diseases. There is evidence to show that postheparin plasma contains enzymes other than LPL. Hence data on total PHLA are difficult to interpret. Availability of assays for the LPL component of PHLA has clarified equivocal findings in certain hypertriglyceridemic states. However, the LPL component is also heterogeneous. The LPL \"isoenzymes\" from various extrahepatic tissues behave differently under various metabolic conditions. Therefore, to understand properly the LPL system it is necessary to study the specific tissue LPL. Furthermore, the serum activator for LPL is now characterized. Its importance is evidenced by the recent discovery of a hypertriglyceridemic patient deficient in this apoprotein."}
{"id": "PMID:207406", "title": "The effectiveness of prophylactic brain irradiation in small cell carcinoma of the lung: a Southwest Oncology Group study.", "content": "Brain involvement in small cell carcinoma of the lung is a common phenomenon occurring in from 29 to 45% of patients. Because of this, it was suggested that prophylactic brain irradiation be made a part of treatment plans for small cell carcinoma. In December 1974, the Southwest Oncology Group (SWOG) began treating patients with combination chemotherapy and irradiation of both the primary lesion and whole brain. In two years, there were 390 patients entered into the study. In patients with extensive disease only 6 of 152 prophylactically irradiated patients developed CNS signs or symptoms of CNS recurrence. In limited disease, 6 of 88 prophylactically treated patients had CNS recurrence and in only 4 was this the site of initial failure. We feel prophylactic brain irradiation in small cell carcinoma of the lung is of benefit.", "contents": "The effectiveness of prophylactic brain irradiation in small cell carcinoma of the lung: a Southwest Oncology Group study. Brain involvement in small cell carcinoma of the lung is a common phenomenon occurring in from 29 to 45% of patients. Because of this, it was suggested that prophylactic brain irradiation be made a part of treatment plans for small cell carcinoma. In December 1974, the Southwest Oncology Group (SWOG) began treating patients with combination chemotherapy and irradiation of both the primary lesion and whole brain. In two years, there were 390 patients entered into the study. In patients with extensive disease only 6 of 152 prophylactically irradiated patients developed CNS signs or symptoms of CNS recurrence. In limited disease, 6 of 88 prophylactically treated patients had CNS recurrence and in only 4 was this the site of initial failure. We feel prophylactic brain irradiation in small cell carcinoma of the lung is of benefit."}
{"id": "PMID:207407", "title": "Carcinomatous versus radiation-induced brachial plexus neuropathy in breast cancer.", "content": "A retrospective study was performed of 18 women in whom ipsilateral brachial plexus neuropathy developed after treatment for carcinoma of the breast. In the absence of metastatic tumor elsewhere, the only distinguishing feature between carcinomatous neuropathy and radiation-induced neuropathy was the symptom-free interval after mastectomy and radiation therapy. Women with an interval of less than a year have radiation-induced neuropathy. Brachial plexus exploration in difficult diagnostic situations will permit early treatment and avoid debilitating loss of function. Brachial plexus exploration for biopsy is safe and free of complications if performed carefully. Treatment of carcinomatous neuropathy is most likely to succeed if the tumor is hormonally sensitive, but radiotherapy may also be effective. Treatment of radiation-induced neuropathy remains largely ineffective.", "contents": "Carcinomatous versus radiation-induced brachial plexus neuropathy in breast cancer. A retrospective study was performed of 18 women in whom ipsilateral brachial plexus neuropathy developed after treatment for carcinoma of the breast. In the absence of metastatic tumor elsewhere, the only distinguishing feature between carcinomatous neuropathy and radiation-induced neuropathy was the symptom-free interval after mastectomy and radiation therapy. Women with an interval of less than a year have radiation-induced neuropathy. Brachial plexus exploration in difficult diagnostic situations will permit early treatment and avoid debilitating loss of function. Brachial plexus exploration for biopsy is safe and free of complications if performed carefully. Treatment of carcinomatous neuropathy is most likely to succeed if the tumor is hormonally sensitive, but radiotherapy may also be effective. Treatment of radiation-induced neuropathy remains largely ineffective."}
{"id": "PMID:207408", "title": "Malignant fibrous histiocytoma: an analysis of 200 cases.", "content": "The clinicopathologic findings in 200 cases of malignant fibrous histiocytoma (MFH) with follow-up information are presented. This tumor occurred principally as a mass on an extremity (lower extremity 49%, upper extremity 19%) or in the abdominal cavity or retroperitoneum (16%) of adults (peak incidence 61-70 years of age). It typically involved deep fascia (19%) or skeletal muscle (59%) and only rarely was confined to the subcutis without fascial involvement (7%). The MFH had variable morphologic features and frequently showed transitions from areas having a highly ordered storiform pattern to less differentiated areas having a pleomorphic appearance. The rate of local recurrence of the tumor was 44%, and of metastasis, 42%. Metastasis was most frequently to the lung (82%) and lymph nodes (32%). Factors that influenced the rate of metastasis included depth, size, and inflammatory component of the tumor. Tumors that were small, superficially located, or had a prominent inflammatory component metastasized less frequently than larger, more deeply located tumors. In our experience the MFH is the most common soft tissue sarcoma of late adult life, and many tumors previously diagnosed as pleomorphic variants of liposarcoma, fibrosarcoma, or rhabdomyosarcoma are probably examples of MFH. Although the histogenesis of this neoplasm remains controversial, we feel it is best regarded as a primitive and pleomorphic sarcoma showing partial fibroblastic and histiocytic differentiation, as reflected by collagen production and occasional phagocytosis.", "contents": "Malignant fibrous histiocytoma: an analysis of 200 cases. The clinicopathologic findings in 200 cases of malignant fibrous histiocytoma (MFH) with follow-up information are presented. This tumor occurred principally as a mass on an extremity (lower extremity 49%, upper extremity 19%) or in the abdominal cavity or retroperitoneum (16%) of adults (peak incidence 61-70 years of age). It typically involved deep fascia (19%) or skeletal muscle (59%) and only rarely was confined to the subcutis without fascial involvement (7%). The MFH had variable morphologic features and frequently showed transitions from areas having a highly ordered storiform pattern to less differentiated areas having a pleomorphic appearance. The rate of local recurrence of the tumor was 44%, and of metastasis, 42%. Metastasis was most frequently to the lung (82%) and lymph nodes (32%). Factors that influenced the rate of metastasis included depth, size, and inflammatory component of the tumor. Tumors that were small, superficially located, or had a prominent inflammatory component metastasized less frequently than larger, more deeply located tumors. In our experience the MFH is the most common soft tissue sarcoma of late adult life, and many tumors previously diagnosed as pleomorphic variants of liposarcoma, fibrosarcoma, or rhabdomyosarcoma are probably examples of MFH. Although the histogenesis of this neoplasm remains controversial, we feel it is best regarded as a primitive and pleomorphic sarcoma showing partial fibroblastic and histiocytic differentiation, as reflected by collagen production and occasional phagocytosis."}
{"id": "PMID:207409", "title": "Mediastinal paragangliomas (aortic body tumor): a report of four cases and a review of the literature.", "content": "Four cases of paraganglioma originating in the supra-aortic or aortico-pulmonary bodies are described. A review of the reported examples of aortic body tumors and a study of these four cases indicate that there is a high incidence of aggressive tumor growth in the mediastinum, with resultant important morbidity or death in 16 of 35 cases. The morphologic features of aortic body tumors are identical to those of paragangliomas of other locations, and the occurrence of invasive growth and/or metastasis cannot be predicted on histologic grounds.", "contents": "Mediastinal paragangliomas (aortic body tumor): a report of four cases and a review of the literature. Four cases of paraganglioma originating in the supra-aortic or aortico-pulmonary bodies are described. A review of the reported examples of aortic body tumors and a study of these four cases indicate that there is a high incidence of aggressive tumor growth in the mediastinum, with resultant important morbidity or death in 16 of 35 cases. The morphologic features of aortic body tumors are identical to those of paragangliomas of other locations, and the occurrence of invasive growth and/or metastasis cannot be predicted on histologic grounds."}
{"id": "PMID:207410", "title": "Primary linitis plastica of the colon: report of two cases and review of the literature.", "content": "Two cases of primary linitis plastica of the large intestine will be presented and discussed. Characteristic clinical features of this type of adenocarcinoma of the large intestine include younger age of presentation, low incidence of hepatic metastasis and a high incidence of ovarian, lymph node and peritoneal metastasis. Pathological features reveal thickening of the intestinal wall by diffuse infiltrating tumor cells of the characteristic signet ring cells, abortive glands and undifferentiated or anaplastic cells. The prognosis is poor.", "contents": "Primary linitis plastica of the colon: report of two cases and review of the literature. Two cases of primary linitis plastica of the large intestine will be presented and discussed. Characteristic clinical features of this type of adenocarcinoma of the large intestine include younger age of presentation, low incidence of hepatic metastasis and a high incidence of ovarian, lymph node and peritoneal metastasis. Pathological features reveal thickening of the intestinal wall by diffuse infiltrating tumor cells of the characteristic signet ring cells, abortive glands and undifferentiated or anaplastic cells. The prognosis is poor."}
{"id": "PMID:207411", "title": "Testicular neoplasms in Kenyan Africans.", "content": "Over a 9-year period 40 testicular and paratesticular neoplasms were seen at the Kenyatta National Hospital, Nairobi, Kenya. Their incidence rate was 0.08 per annum per 100,000 Kenyan males. This low incidence was largely accounted for by a decrease in tumors of germ cell origin. The proportional distribution of the testicular neoplasms, however, was not significantly different from findings in the United States. An inheritable factor apparently controls the decreased susceptability to testicular neoplasms.", "contents": "Testicular neoplasms in Kenyan Africans. Over a 9-year period 40 testicular and paratesticular neoplasms were seen at the Kenyatta National Hospital, Nairobi, Kenya. Their incidence rate was 0.08 per annum per 100,000 Kenyan males. This low incidence was largely accounted for by a decrease in tumors of germ cell origin. The proportional distribution of the testicular neoplasms, however, was not significantly different from findings in the United States. An inheritable factor apparently controls the decreased susceptability to testicular neoplasms."}
{"id": "PMID:207412", "title": "Hepatocarcinogenicity of polychlorinated terphenyl (PCT) in ICR mice and its enhancement by hexachlorobenzene (HCB).", "content": "Studies were made on the carcinogenic effects of hexachlorobenzene (HCB) and polychlorinated terphenyl (PCT) singly and in combination when given orally to mice for 24 weeks. PCT alone induced liver tumors, nodular hyperplasias and hepatocellular carcinomas. HCB alone had no effect, but it enhanced the induction of liver tumors by PCT.", "contents": "Hepatocarcinogenicity of polychlorinated terphenyl (PCT) in ICR mice and its enhancement by hexachlorobenzene (HCB). Studies were made on the carcinogenic effects of hexachlorobenzene (HCB) and polychlorinated terphenyl (PCT) singly and in combination when given orally to mice for 24 weeks. PCT alone induced liver tumors, nodular hyperplasias and hepatocellular carcinomas. HCB alone had no effect, but it enhanced the induction of liver tumors by PCT."}
{"id": "PMID:207413", "title": "Effects of culture conditions on the growth and differentiation of transformed rat adrenocortical cells.", "content": "Normal rat adrenocortical cells grow in vitro in two states of differentiation, depending on culture conditions. Under one set of conditions, they proliferate and are fibroblast shaped, with some myoid cell characteristics and with limited steroidogenic activity. Under alternate conditions they do not replicate and are epithelial-like and similar to adrenocortical secretory cells structurally and steroidogenically. The effects of oncogenic transformation on these cellular responses to culture variables were examined by using the Kirsten murine sarcoma virus-transformed rat adrenocortical line TRA. Transformation eliminated the differential proliferative response of the cells to culture variables and resulted in similar growth rates and high cell densities under all conditions. Horse serum, conducive to epithelial-like growth of nontransformed cells, caused aggregation, whereas fetal calf serum, conducive to fibroblastic growth of untransformed cells, caused dispersed growth in TRA cultures. Variations in dissociation procedures had little effect on growth patterns. Most ultrastructural characteristics of myoid as well as adrenocoritcal differentiation were reduced in TRA cells, although basement membranes and extracellular matrix were produced, but under different conditions than in untransformed cultures. Like normal adrenocortical cells, TRA cells were capable of 20alpha-reduction and delta5-3-beta-dehydrogenation of [4-14C5pregnenolone but, in contrast to untransformed cells, they did not respond to variables in culture conditions by qualitative changes in pregnenolone metabolism, did not produce deoxycorticosterone or corticosterone, and secreted progesterone, a hormone not recovered from untransformed cultures. TRA cells showed no increase in steroidogenic differentiation in response to those culture environment factors that normally cause modulation of the fibroblast-shaped adrenocortical stem cells to more differentiated steroid-secreting cells.", "contents": "Effects of culture conditions on the growth and differentiation of transformed rat adrenocortical cells. Normal rat adrenocortical cells grow in vitro in two states of differentiation, depending on culture conditions. Under one set of conditions, they proliferate and are fibroblast shaped, with some myoid cell characteristics and with limited steroidogenic activity. Under alternate conditions they do not replicate and are epithelial-like and similar to adrenocortical secretory cells structurally and steroidogenically. The effects of oncogenic transformation on these cellular responses to culture variables were examined by using the Kirsten murine sarcoma virus-transformed rat adrenocortical line TRA. Transformation eliminated the differential proliferative response of the cells to culture variables and resulted in similar growth rates and high cell densities under all conditions. Horse serum, conducive to epithelial-like growth of nontransformed cells, caused aggregation, whereas fetal calf serum, conducive to fibroblastic growth of untransformed cells, caused dispersed growth in TRA cultures. Variations in dissociation procedures had little effect on growth patterns. Most ultrastructural characteristics of myoid as well as adrenocoritcal differentiation were reduced in TRA cells, although basement membranes and extracellular matrix were produced, but under different conditions than in untransformed cultures. Like normal adrenocortical cells, TRA cells were capable of 20alpha-reduction and delta5-3-beta-dehydrogenation of [4-14C5pregnenolone but, in contrast to untransformed cells, they did not respond to variables in culture conditions by qualitative changes in pregnenolone metabolism, did not produce deoxycorticosterone or corticosterone, and secreted progesterone, a hormone not recovered from untransformed cultures. TRA cells showed no increase in steroidogenic differentiation in response to those culture environment factors that normally cause modulation of the fibroblast-shaped adrenocortical stem cells to more differentiated steroid-secreting cells."}
{"id": "PMID:207414", "title": "Comparison of thioredoxin reductases from Novikoff ascites hepatoma cells and normal liver of rats.", "content": "Adult rat liver contained variant forms of thioredoxin reductase with isoelectric points at pH 4.9 and at approximately pH 4.7 compared to pH 5.1 for the enzyme from Novikoff ascites hepatoma. Fetal and regenerating liver contained only the form with the isoelectric point at pH 4.9. All three enzymes precipitated with and were inhibited by a rabbit antibody to purified enzyme from Novikoff tumor.", "contents": "Comparison of thioredoxin reductases from Novikoff ascites hepatoma cells and normal liver of rats. Adult rat liver contained variant forms of thioredoxin reductase with isoelectric points at pH 4.9 and at approximately pH 4.7 compared to pH 5.1 for the enzyme from Novikoff ascites hepatoma. Fetal and regenerating liver contained only the form with the isoelectric point at pH 4.9. All three enzymes precipitated with and were inhibited by a rabbit antibody to purified enzyme from Novikoff tumor."}
{"id": "PMID:207415", "title": "Induction of colonic adenocarcinoma in the rat by X-irradiation.", "content": "In work to determine whether X-radiation could be used to induce tumors of the colon in outbred Holtzman rats, a technique was devised so that only the descending colon could be irradiated with a collimated X-ray beam and tumorigenic exposures in the kilo-Roentgen range were delivered. Ninety male Holtzman rats were divided into 6 exposure groups of 15 animals each. In the first group only the colon was exposed to 2500 R; in the second group the colon was exposed to 3500 R and the exposures were increased by 1000-R increments up through 6500 R; the sixth group was sham irradiated. Animals in each of the irradited groups developed mucoid adenocarcinomas with the highest incidence (47%) obtained inthe 4500-R group. Histopathologically, the induced tumors bear a close resemblance to human colon adenocarcinoma, and the development of pulmonary metastases in one of the animals with multiple primary tumors demonstrated their malignancy. The usefulness of the animal model is discussed.", "contents": "Induction of colonic adenocarcinoma in the rat by X-irradiation. In work to determine whether X-radiation could be used to induce tumors of the colon in outbred Holtzman rats, a technique was devised so that only the descending colon could be irradiated with a collimated X-ray beam and tumorigenic exposures in the kilo-Roentgen range were delivered. Ninety male Holtzman rats were divided into 6 exposure groups of 15 animals each. In the first group only the colon was exposed to 2500 R; in the second group the colon was exposed to 3500 R and the exposures were increased by 1000-R increments up through 6500 R; the sixth group was sham irradiated. Animals in each of the irradited groups developed mucoid adenocarcinomas with the highest incidence (47%) obtained inthe 4500-R group. Histopathologically, the induced tumors bear a close resemblance to human colon adenocarcinoma, and the development of pulmonary metastases in one of the animals with multiple primary tumors demonstrated their malignancy. The usefulness of the animal model is discussed."}
{"id": "PMID:207416", "title": "Deoxyadenosine antagonism of the antiviral activity of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosylhypoxanthine.", "content": "Deoxyadenosine but not adenosine reversed the antiviral activity of 9-beta-D-arabinofuranosyladenine (ara-A) and 9-beta-D-arabinofuranosylhypoxanthine (ara-H) when used in the presence of coformycin, an inhibitor of adenosine deaminase. In suspension cultures of KB cells, 10 muM ara-A inhibited the replication of herpes simplex virus type 1 by 80%. Concomitant addition of 50 muM deoxyadenosine reduced the antiviral activity of 10 muM ara-A to only 40% inhibition. Adenosine failed to antagonize the antiviral activity. In monolayer cultures of KB cells, the 50% inhibitory concentration of ara-A was increased from 1.5 to 2.9 muM by 2 muM deoxyadenosine and to 8.5 muM by 10 muM deoxyadenosine. Analysis of the dose-response data by a double reciprocal plot method indicated that the antagonism was competitive. The antiviral activity of ara-H also was antagonized by deoxyadenosine. The 50% inhibitory concentration of ara-H was increased from 42 muM to 70, 91, or 121 muM by the concurrent addition of 5, 10, or 20 muM deoxyadenosine. Competitive antagonism could not be demonstrated. In the absence of the adenosine deaminase inhibitor, neither ara-A nor ara-H was antagonized by deoxyadenosine. Since such inhibitors were not available unitl recently, previous investigators were unable to observe the antagonistic capacity of deoxyadenosine.", "contents": "Deoxyadenosine antagonism of the antiviral activity of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosylhypoxanthine. Deoxyadenosine but not adenosine reversed the antiviral activity of 9-beta-D-arabinofuranosyladenine (ara-A) and 9-beta-D-arabinofuranosylhypoxanthine (ara-H) when used in the presence of coformycin, an inhibitor of adenosine deaminase. In suspension cultures of KB cells, 10 muM ara-A inhibited the replication of herpes simplex virus type 1 by 80%. Concomitant addition of 50 muM deoxyadenosine reduced the antiviral activity of 10 muM ara-A to only 40% inhibition. Adenosine failed to antagonize the antiviral activity. In monolayer cultures of KB cells, the 50% inhibitory concentration of ara-A was increased from 1.5 to 2.9 muM by 2 muM deoxyadenosine and to 8.5 muM by 10 muM deoxyadenosine. Analysis of the dose-response data by a double reciprocal plot method indicated that the antagonism was competitive. The antiviral activity of ara-H also was antagonized by deoxyadenosine. The 50% inhibitory concentration of ara-H was increased from 42 muM to 70, 91, or 121 muM by the concurrent addition of 5, 10, or 20 muM deoxyadenosine. Competitive antagonism could not be demonstrated. In the absence of the adenosine deaminase inhibitor, neither ara-A nor ara-H was antagonized by deoxyadenosine. Since such inhibitors were not available unitl recently, previous investigators were unable to observe the antagonistic capacity of deoxyadenosine."}
{"id": "PMID:207417", "title": "Isolation and characterization of a cytosol protein (64/7.2) present in large amounts in rapidly growing hepatomas.", "content": "Protein 64/7.2 (molecular weight/isoelectric point) is present in the cytosol of several hepatomas including the Novikoff hepatoma and Morris hepatomas 9618A, 7794A, and 3924A, but it is not present in liver or 18-hr regenerating liver. Quantitatively, its concentration was highest in Novikoff hepatoma (150 microgram/g tissue) and Morris hepatoma 3924A (550 microgram/g tissue), which are rapid-growing tumors, less in Morris hepatoma 7794A (72 microgram/g tissue), which is of intermediate growth rate, and least in the slow-growing Morris hepatoma 9618A (25 microgram/g tissue). Protein 64/7.2 was isolated from Novikoff hepatoma ascites cells in high purity as shown by its migration as a single band on one-dimensional acid-urea-polyacrylamide gels and a single spot on two-dimensional isoelectric focusing sodium dodecyl sulfate-polyacrylamide gels. Its amino acid composition has an acidic to basic amino acid ratio of 1.6. Its amino-terminal amino acid is lysine, and its carboxyl-terminal amino acid is glycine. Interestingly, the amino acid composition is strikingly similar to that of the phosphorylated Novikoff hepatoma chromatin Protein Cg', partially characterized in our laboratory.", "contents": "Isolation and characterization of a cytosol protein (64/7.2) present in large amounts in rapidly growing hepatomas. Protein 64/7.2 (molecular weight/isoelectric point) is present in the cytosol of several hepatomas including the Novikoff hepatoma and Morris hepatomas 9618A, 7794A, and 3924A, but it is not present in liver or 18-hr regenerating liver. Quantitatively, its concentration was highest in Novikoff hepatoma (150 microgram/g tissue) and Morris hepatoma 3924A (550 microgram/g tissue), which are rapid-growing tumors, less in Morris hepatoma 7794A (72 microgram/g tissue), which is of intermediate growth rate, and least in the slow-growing Morris hepatoma 9618A (25 microgram/g tissue). Protein 64/7.2 was isolated from Novikoff hepatoma ascites cells in high purity as shown by its migration as a single band on one-dimensional acid-urea-polyacrylamide gels and a single spot on two-dimensional isoelectric focusing sodium dodecyl sulfate-polyacrylamide gels. Its amino acid composition has an acidic to basic amino acid ratio of 1.6. Its amino-terminal amino acid is lysine, and its carboxyl-terminal amino acid is glycine. Interestingly, the amino acid composition is strikingly similar to that of the phosphorylated Novikoff hepatoma chromatin Protein Cg', partially characterized in our laboratory."}
{"id": "PMID:207419", "title": "Morphology and metastatic nature of induced hepatic nodular lesions in C57BL x C3H F1 mice.", "content": "The metastatic capabilities of well-defined nodular hepatic lesions induced by benzo(a)pyrene, ethylnitrosourea, benzidine.2HCl, and diethylnitrosamine were evaluated. Coded liver and lung tissues from 1264 treated C57BL/6J x C3HeB/FeJ F1 mice were assessed independently for the presence of primary nodular lesions and metastases, respectively. Primary lesions were classified according to their size, cell morphology, and growth patterns into hyperplastic, adenomatous, and trabecular nodules. None of the 126 mice bearing hyperplastic nodules had pulmonary metastases. Four of 291 (1.4%) mice with adenomatous nodular lesions showed metastases. In contrast, of the 733 mice bearing the trabecular type of nodular lesions alone or in combination with other lesions 266 (36%) showed pulmonary metastases. The pulmonary metastases were first detected in mice dying between 51 and 60 weeks of age (5%). This rate increased as a function of age at death, reaching an incidence of 51% in mice surviving more than 81 weeks. It was concluded that nodules showing trabecular and the more anaplastic solid sheet type of growths represented bona fide hepatocellular carcinomas in the mouse.", "contents": "Morphology and metastatic nature of induced hepatic nodular lesions in C57BL x C3H F1 mice. The metastatic capabilities of well-defined nodular hepatic lesions induced by benzo(a)pyrene, ethylnitrosourea, benzidine.2HCl, and diethylnitrosamine were evaluated. Coded liver and lung tissues from 1264 treated C57BL/6J x C3HeB/FeJ F1 mice were assessed independently for the presence of primary nodular lesions and metastases, respectively. Primary lesions were classified according to their size, cell morphology, and growth patterns into hyperplastic, adenomatous, and trabecular nodules. None of the 126 mice bearing hyperplastic nodules had pulmonary metastases. Four of 291 (1.4%) mice with adenomatous nodular lesions showed metastases. In contrast, of the 733 mice bearing the trabecular type of nodular lesions alone or in combination with other lesions 266 (36%) showed pulmonary metastases. The pulmonary metastases were first detected in mice dying between 51 and 60 weeks of age (5%). This rate increased as a function of age at death, reaching an incidence of 51% in mice surviving more than 81 weeks. It was concluded that nodules showing trabecular and the more anaplastic solid sheet type of growths represented bona fide hepatocellular carcinomas in the mouse."}
{"id": "PMID:207422", "title": "A comparison of polysomal messenger ribonucleoprotein particles from normal and neoplastic rat liver.", "content": "Free polysomes were isolated from normal and regenerating rat liver and from Morris hepatomas 7777, 7800, 5123C and 9618A. Sucrose gradient analysis ruled out the possibility of any significant messenger RNA degradation in these polysome preparations. The ethylenediaminetetraacetate-disrupted polysomes were fractionated on oligodeoxythymidylic acid-cellulose columns. The column-bound polyriboadenylic acid-containing messenger ribonucleoprotein particles were eluted with a formamide buffer, precipitated with ethanol, and subjected to polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The messenger RNA-associated proteins from the different tissues were qualitatively similar, but two proteins with molecular weights of 66,000 and 109,000 found as minor proteins in normal liver appeared on gels as major protein bands when hepatoma messenger ribonucleoprotein particles were examined. The 66,000- and 109,000-molecular-weight proteins in these particles from regenerating liver appeared quantitatively similar to those isolated from normal liver.", "contents": "A comparison of polysomal messenger ribonucleoprotein particles from normal and neoplastic rat liver. Free polysomes were isolated from normal and regenerating rat liver and from Morris hepatomas 7777, 7800, 5123C and 9618A. Sucrose gradient analysis ruled out the possibility of any significant messenger RNA degradation in these polysome preparations. The ethylenediaminetetraacetate-disrupted polysomes were fractionated on oligodeoxythymidylic acid-cellulose columns. The column-bound polyriboadenylic acid-containing messenger ribonucleoprotein particles were eluted with a formamide buffer, precipitated with ethanol, and subjected to polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The messenger RNA-associated proteins from the different tissues were qualitatively similar, but two proteins with molecular weights of 66,000 and 109,000 found as minor proteins in normal liver appeared on gels as major protein bands when hepatoma messenger ribonucleoprotein particles were examined. The 66,000- and 109,000-molecular-weight proteins in these particles from regenerating liver appeared quantitatively similar to those isolated from normal liver."}
{"id": "PMID:207423", "title": "Detection of inapparent nodule-transformed cells in the mammary gland tissues of virgin female BALB/cfC3H mice.", "content": "Inapparent nodule-transformed cells were recovered from morphologically normal mammary tissue from virgin female BALB/cfC3H/Crgl (mouse mammary tumor-positive) mice before the appearance of hyperplastic alveolar nodules (HAN) or tumors, by means of the cell dissociation technique. Mammary tissues were dissociated by means of collagenase (0.1%), hyaluronidase (0.1%), and pronase (1.25%). Aliquots of 10(5) viable cells in 0.01 ml medium were injected into the gland-free mammary fat pads of 3-week-old female syngeneic mice. After 10 weeks the outgrowths were examined and classified as ductal, HAN, tumor, or combinations of these types. The presence of HAN outgrowths indicated the presence of nodule-transformed cells in the donor mammary tissues. Nodule-transformed cells were recovered from 2-month-old donors, and the number of HAN outgrowths increased with donor age. Overt HAN and tumors did not appear in virgin female BALB/cfC3H/Crgl mice younger than 8 to 9 months of age. The data suggest that inapparent nodule-transformed cells occurred long before the appearance of HAN of tumors and that the numbers of transformed cells increased with donor age.", "contents": "Detection of inapparent nodule-transformed cells in the mammary gland tissues of virgin female BALB/cfC3H mice. Inapparent nodule-transformed cells were recovered from morphologically normal mammary tissue from virgin female BALB/cfC3H/Crgl (mouse mammary tumor-positive) mice before the appearance of hyperplastic alveolar nodules (HAN) or tumors, by means of the cell dissociation technique. Mammary tissues were dissociated by means of collagenase (0.1%), hyaluronidase (0.1%), and pronase (1.25%). Aliquots of 10(5) viable cells in 0.01 ml medium were injected into the gland-free mammary fat pads of 3-week-old female syngeneic mice. After 10 weeks the outgrowths were examined and classified as ductal, HAN, tumor, or combinations of these types. The presence of HAN outgrowths indicated the presence of nodule-transformed cells in the donor mammary tissues. Nodule-transformed cells were recovered from 2-month-old donors, and the number of HAN outgrowths increased with donor age. Overt HAN and tumors did not appear in virgin female BALB/cfC3H/Crgl mice younger than 8 to 9 months of age. The data suggest that inapparent nodule-transformed cells occurred long before the appearance of HAN of tumors and that the numbers of transformed cells increased with donor age."}
{"id": "PMID:207424", "title": "Tumorigenic action of streptozotocin on the pancreas and kidney in male Wistar rats.", "content": "Pancreatic islet cell tumors were induced in 38 of 44 male Wistar rats (86%), which survived 9 to 14 months following the various treatment schedules. A single i.v. injection of streptozotocin alone, 30, 40, 50, or 65 mg/kg of body weight produced adenomas of pancreatic islet cells in 8 of 9 (89%), 6 of 7 (86%), 2 of 4 (50%), and 1 of 2 rats (50%), respectively. The neoplasms were seen in all of the 8 rats given a single i.p. injection of picolinamide, 250 mg/kg of body weight, 15 min before a single i.v. injection of streptozotocin, 65 mg/kg of body weight. Among the 14 rats given a single i.p. injection of nicotinamide, 500 mg/kg of body weight, 15 min before a single i.v. injection of streptozotocin, 65 mg/kg of body weight, 13 rats (95%) developed pancreatic islet cell tumors. Renal tumors were seen in only 3 rats treated with streptozotocin and nicotinamide. None of rats used in this study developed hepatic tumors. This study demonstrates that steptozotocin, even in a dose of 30 mg/kg of body weight, has an exceedingly marked tumorigenic action on the rat pancreas, while it has little effect on the kidney and no effect on the liver.", "contents": "Tumorigenic action of streptozotocin on the pancreas and kidney in male Wistar rats. Pancreatic islet cell tumors were induced in 38 of 44 male Wistar rats (86%), which survived 9 to 14 months following the various treatment schedules. A single i.v. injection of streptozotocin alone, 30, 40, 50, or 65 mg/kg of body weight produced adenomas of pancreatic islet cells in 8 of 9 (89%), 6 of 7 (86%), 2 of 4 (50%), and 1 of 2 rats (50%), respectively. The neoplasms were seen in all of the 8 rats given a single i.p. injection of picolinamide, 250 mg/kg of body weight, 15 min before a single i.v. injection of streptozotocin, 65 mg/kg of body weight. Among the 14 rats given a single i.p. injection of nicotinamide, 500 mg/kg of body weight, 15 min before a single i.v. injection of streptozotocin, 65 mg/kg of body weight, 13 rats (95%) developed pancreatic islet cell tumors. Renal tumors were seen in only 3 rats treated with streptozotocin and nicotinamide. None of rats used in this study developed hepatic tumors. This study demonstrates that steptozotocin, even in a dose of 30 mg/kg of body weight, has an exceedingly marked tumorigenic action on the rat pancreas, while it has little effect on the kidney and no effect on the liver."}
{"id": "PMID:207425", "title": "Carcinostatic effect of aliphatic aldehydes and aldehyde dehydrogenase activity in Ehrlich carcinoma, Sarcoma 180, and Yoshida AH 130 hepatoma.", "content": "The antitumor activity of 2,3-dihydroxybutyraldehyde on Ehrlich carcinoma, Sarcoma 180, and Yoshida AH 130 hepatoma, as well as the aldehyde dehydrogenase activity in these tumors, was studied. 2,3-Dihydroxybutyraldehyde at nontoxic doses (500 mg/kg body weight i.p. daily for 7 days) slowed down the growth of solid and ascites tumors in mice. The treatment completely prevented the development of Yoshida ascites hepatoma in several rats. 2,3-Dihydroxybutyraldehyde, although it did not influence the growth of Ehrlich carcinoma transplanted in the brain of mice, significantly decreased in the lungs of these animals the number of viable tumour cells that derived from the primary tumor. All the tested tumors, which were sensitive to the action of 2,3-dihydroxybutyraldehyde, were virtually devoid of aldehyde dehydrogenase activity. These results suggest a possible relationship between the lack of this enzyme activity and the antitumor activity of aliphatic aldehydes.", "contents": "Carcinostatic effect of aliphatic aldehydes and aldehyde dehydrogenase activity in Ehrlich carcinoma, Sarcoma 180, and Yoshida AH 130 hepatoma. The antitumor activity of 2,3-dihydroxybutyraldehyde on Ehrlich carcinoma, Sarcoma 180, and Yoshida AH 130 hepatoma, as well as the aldehyde dehydrogenase activity in these tumors, was studied. 2,3-Dihydroxybutyraldehyde at nontoxic doses (500 mg/kg body weight i.p. daily for 7 days) slowed down the growth of solid and ascites tumors in mice. The treatment completely prevented the development of Yoshida ascites hepatoma in several rats. 2,3-Dihydroxybutyraldehyde, although it did not influence the growth of Ehrlich carcinoma transplanted in the brain of mice, significantly decreased in the lungs of these animals the number of viable tumour cells that derived from the primary tumor. All the tested tumors, which were sensitive to the action of 2,3-dihydroxybutyraldehyde, were virtually devoid of aldehyde dehydrogenase activity. These results suggest a possible relationship between the lack of this enzyme activity and the antitumor activity of aliphatic aldehydes."}
{"id": "PMID:207426", "title": "Influence of dietary protein and vitamin B12 on the toxicity and carcinogenicity of aflatoxins in rat liver.", "content": "The influence of dietary protein content and dietary vitamin B12 supplement on the hepatotoxicity and carcinogenicity of aflatoxin in rat liver was studied. In animals fed a low-protein diet, aflatoxin induced extensive toxic and carcinogenic effects. Cirrhosis was significantly prevented to a certain level by vitamin B12 administration, but the incidence of cholangiofibrosis and hyperplastic nodules was unchanged. No toxic effect was observed in animals receiving high-protein diet with no vitamin B12 supplement in this study (33 weeks). Only one rat bearing a hepatoma was observed in this group. However, hepatoma and hyperplastic nodules were found in the group receiving high-protein diet plus vitamin B12. Cholangiofibrosis and cirrhosis were not observed in the high-protein group regardless of vitamin B12 administration.", "contents": "Influence of dietary protein and vitamin B12 on the toxicity and carcinogenicity of aflatoxins in rat liver. The influence of dietary protein content and dietary vitamin B12 supplement on the hepatotoxicity and carcinogenicity of aflatoxin in rat liver was studied. In animals fed a low-protein diet, aflatoxin induced extensive toxic and carcinogenic effects. Cirrhosis was significantly prevented to a certain level by vitamin B12 administration, but the incidence of cholangiofibrosis and hyperplastic nodules was unchanged. No toxic effect was observed in animals receiving high-protein diet with no vitamin B12 supplement in this study (33 weeks). Only one rat bearing a hepatoma was observed in this group. However, hepatoma and hyperplastic nodules were found in the group receiving high-protein diet plus vitamin B12. Cholangiofibrosis and cirrhosis were not observed in the high-protein group regardless of vitamin B12 administration."}
{"id": "PMID:207427", "title": "Peripheral neuropathy as a complication of cis-dichlorodiammineplatinum(II) treatment: a case report.", "content": "A 19-year-old woman with a diagnosis of osteosarcoma was initially treated with amputation of her right leg and adjuvant adriamycin. She developed pulmonary metastases 18 months following diagnosis. She was then given cis-dichlorodiammineplatinum(II) (DDP) at a dose of 100 mg/m2 iv approximately every 4 weeks as the sole drug. Following the fifth dose of DDP, she complained of numbness and tingling in her hands and leg. A distal sensory loss extending to both elbows and her remaining knee was found on examination. Nerve conduction tests were compatible with peripheral neuropathy of the \"glove and stocking\" type. DDP was withheld and her sensory loss improved over the next 2 months, but became worse after another course of DDP was administered. The temporal relationship between the findings and the administration of DDP implicates this drug as the causative agent in the peripheral neuropathy.", "contents": "Peripheral neuropathy as a complication of cis-dichlorodiammineplatinum(II) treatment: a case report. A 19-year-old woman with a diagnosis of osteosarcoma was initially treated with amputation of her right leg and adjuvant adriamycin. She developed pulmonary metastases 18 months following diagnosis. She was then given cis-dichlorodiammineplatinum(II) (DDP) at a dose of 100 mg/m2 iv approximately every 4 weeks as the sole drug. Following the fifth dose of DDP, she complained of numbness and tingling in her hands and leg. A distal sensory loss extending to both elbows and her remaining knee was found on examination. Nerve conduction tests were compatible with peripheral neuropathy of the \"glove and stocking\" type. DDP was withheld and her sensory loss improved over the next 2 months, but became worse after another course of DDP was administered. The temporal relationship between the findings and the administration of DDP implicates this drug as the causative agent in the peripheral neuropathy."}
{"id": "PMID:207431", "title": "Investigations into the mechanism of hormone release by rat adrenocortical cells.", "content": "Vinblastine treatment blocks corticosterone release from rat adrenal zona fasciculata without impairing hormone synthesis, and induces the formation of acid phosphatase-positive granular clumps at the juxta-sinusoidal pole of the cells. Autoradiography shows that ACTH administration to vinblastine-treated animals mobilizes the 3H-cholesterol stored in the lipid droplets and leads to a noticeable labelling of the granular clumps. The possible significance of these granules is discussed.", "contents": "Investigations into the mechanism of hormone release by rat adrenocortical cells. Vinblastine treatment blocks corticosterone release from rat adrenal zona fasciculata without impairing hormone synthesis, and induces the formation of acid phosphatase-positive granular clumps at the juxta-sinusoidal pole of the cells. Autoradiography shows that ACTH administration to vinblastine-treated animals mobilizes the 3H-cholesterol stored in the lipid droplets and leads to a noticeable labelling of the granular clumps. The possible significance of these granules is discussed."}
{"id": "PMID:207433", "title": "Introduction of the herpes simplex virus thymidine kinase gene into mouse cells using virus DNA or transformed cell DNA.", "content": "Cells lacking the enzyme thymidine kinase (LMTK- cells) have been transformed to a kinase-positive phenotype using sheared herpes simplex virus (HSV) DNA, and the enzyme found in these transformed cells is HSV-specific. One of the cell lines is able to complement the functional defect found in two temperature-sensitive mutants of HSV 1, and reversion of the cells to a thymidine kinase-negative phenotype results in the loss of this capability. The HSV thymidine kinase gene can also be introduced into LMTK- cells using DNA extracted from transformed cells, and the high efficiency of this procedure suggests that the state of the virus DNA in transformed cells is different from that of DNA in virus particles.", "contents": "Introduction of the herpes simplex virus thymidine kinase gene into mouse cells using virus DNA or transformed cell DNA. Cells lacking the enzyme thymidine kinase (LMTK- cells) have been transformed to a kinase-positive phenotype using sheared herpes simplex virus (HSV) DNA, and the enzyme found in these transformed cells is HSV-specific. One of the cell lines is able to complement the functional defect found in two temperature-sensitive mutants of HSV 1, and reversion of the cells to a thymidine kinase-negative phenotype results in the loss of this capability. The HSV thymidine kinase gene can also be introduced into LMTK- cells using DNA extracted from transformed cells, and the high efficiency of this procedure suggests that the state of the virus DNA in transformed cells is different from that of DNA in virus particles."}
{"id": "PMID:207434", "title": "Specific changes in the oligosaccharide moieties of VSV grown in different lectin-resistnat CHO cells.", "content": "The carbohydrate moieties of the G glycoprotein of vesicular stomatitis virus (VSV) grown in three distinct lectin-resistant (LecR) Chinese hamster ovary (CHO) cell lines have been compared by fine structural analysis of radiolabeled glycopeptides. The mutant WgaRIII, selected for resistance to wheat germ agglutinin (WGA), produces VSV containing G glycoprotein specifically lacking in sialic acid. The mutant PhaRI, selected for resistance to phytohemagglutinin (PHA) and previously shown to lack a particular glycoprotein N-acetyl-glucosaminyl-transferase activity, produces VSV containing G glycoprotein specifically lacking terminal N-acetylglucosamine-galactose-sialic acid sequences and possessing an increased number of mannose residues in the \"core\" region of its carbohydrate moieties. The mutant PhaRIConARII, a \"double\" mutant selected from PhaRI cells for resistance to concanavalin A (ConA), produces VSV containing G glycoprotein with a further alteration in the mannose residues of the \"core\" oligosaccharide region. We discuss the relevance of these findings to the mechanisms of glycoprotein biosynthesis in mammalian cells and to the biochemical bases of lectin resistance in CHO cells.", "contents": "Specific changes in the oligosaccharide moieties of VSV grown in different lectin-resistnat CHO cells. The carbohydrate moieties of the G glycoprotein of vesicular stomatitis virus (VSV) grown in three distinct lectin-resistant (LecR) Chinese hamster ovary (CHO) cell lines have been compared by fine structural analysis of radiolabeled glycopeptides. The mutant WgaRIII, selected for resistance to wheat germ agglutinin (WGA), produces VSV containing G glycoprotein specifically lacking in sialic acid. The mutant PhaRI, selected for resistance to phytohemagglutinin (PHA) and previously shown to lack a particular glycoprotein N-acetyl-glucosaminyl-transferase activity, produces VSV containing G glycoprotein specifically lacking terminal N-acetylglucosamine-galactose-sialic acid sequences and possessing an increased number of mannose residues in the \"core\" region of its carbohydrate moieties. The mutant PhaRIConARII, a \"double\" mutant selected from PhaRI cells for resistance to concanavalin A (ConA), produces VSV containing G glycoprotein with a further alteration in the mannose residues of the \"core\" oligosaccharide region. We discuss the relevance of these findings to the mechanisms of glycoprotein biosynthesis in mammalian cells and to the biochemical bases of lectin resistance in CHO cells."}
{"id": "PMID:207432", "title": "Effects of tropic hormones on ultrastructure and synthesis of androgens in adrenals of male pseudohermaphrodite rats.", "content": "Ultrastructural and biochemical study of the adrenals in the pseudohermaphrodite (tfm) rat reveals hypertrophic adrenocortical cells. The cytoplasm of the cells in the zonae fasciculata and reticularis contains an exceptionally well developed smooth endoplasmic reticulum closely applied to mitochondria and lipid droplets. Mitochondria are more numerous than in normals and have especially abundant tubular cristae. More lipid droplets (appearing as empty vacuoles) are surrounded by pleomorphic mitochondria. The incubation study indicates that the capacity of rat adrenal cortex of producing androgens is greater in tfm than in normal animals. Hypophysectomy and castration result in a significant decrease in androgen biosynthesis by tfm rat adrenals and cause a reduced concentration of plasma testosterone. Administration of tropic hormones to hypophysectomized-castrated rats appears to stimulate their adrenal androgenesis. It is suggested that in tfm rats the higher than normal luteinizing hormone (LH) together with adrenocorticotropic hormone (ACTH) stimulates the hypertrophy of cellular organelles in the adrenal cortex and causes an accompanying increase in androgenic steroids which may be responsible, at least in part, for the increased level of plasma androgens.", "contents": "Effects of tropic hormones on ultrastructure and synthesis of androgens in adrenals of male pseudohermaphrodite rats. Ultrastructural and biochemical study of the adrenals in the pseudohermaphrodite (tfm) rat reveals hypertrophic adrenocortical cells. The cytoplasm of the cells in the zonae fasciculata and reticularis contains an exceptionally well developed smooth endoplasmic reticulum closely applied to mitochondria and lipid droplets. Mitochondria are more numerous than in normals and have especially abundant tubular cristae. More lipid droplets (appearing as empty vacuoles) are surrounded by pleomorphic mitochondria. The incubation study indicates that the capacity of rat adrenal cortex of producing androgens is greater in tfm than in normal animals. Hypophysectomy and castration result in a significant decrease in androgen biosynthesis by tfm rat adrenals and cause a reduced concentration of plasma testosterone. Administration of tropic hormones to hypophysectomized-castrated rats appears to stimulate their adrenal androgenesis. It is suggested that in tfm rats the higher than normal luteinizing hormone (LH) together with adrenocorticotropic hormone (ACTH) stimulates the hypertrophy of cellular organelles in the adrenal cortex and causes an accompanying increase in androgenic steroids which may be responsible, at least in part, for the increased level of plasma androgens."}
{"id": "PMID:207435", "title": "Identification of a transformation-specific protein induced by a Rous sarcoma virus.", "content": "Using antisera obtained from rats bearing Schmidt-Ruppin strain Rous sarcoma virus-induced tumors, we have idnetified a protein with an apparent molecular weight of 56,000 daltons and an isoelectric point of 6.3 in extracts of chick embryo fibroblasts transformed by a wild-type nondefective Rous sarcoma virus (Schmidt-Ruppin strain). This protein was not found in cells infected by trnasformation-defective mutants with either a partial or complete deletion of the src gene, nor in cells infected by a nontransforming avian leukosis virus. The 56,000 dalton molecular weight protein was found to be synthesized at both the permissive and nonpermissive temperatures in cells infected by either of two conditionallethal mutants that are temperature-sensitive in cell transformation. The amount of this protein, however, accumulated in cells infected by these temperature-sensitive mutants, relative to the structural polypeptides, differed significnatly from that seen with the nondefective virus. Pulsechase experiments indicate that the protein is extremely unstable, with a half-life of about 20 min, and does not serve as a precursor to any of the detectable virion polypeptides. Furthermore, incubation of the rat antiserum with purified, disrupted virus did not affect its immunoreactivity to this particular protein. We conclude that this 56,000 dalton molecular weight protein is a nonstructural protein specific to cells transformed by Rous sarcoma virus.", "contents": "Identification of a transformation-specific protein induced by a Rous sarcoma virus. Using antisera obtained from rats bearing Schmidt-Ruppin strain Rous sarcoma virus-induced tumors, we have idnetified a protein with an apparent molecular weight of 56,000 daltons and an isoelectric point of 6.3 in extracts of chick embryo fibroblasts transformed by a wild-type nondefective Rous sarcoma virus (Schmidt-Ruppin strain). This protein was not found in cells infected by trnasformation-defective mutants with either a partial or complete deletion of the src gene, nor in cells infected by a nontransforming avian leukosis virus. The 56,000 dalton molecular weight protein was found to be synthesized at both the permissive and nonpermissive temperatures in cells infected by either of two conditionallethal mutants that are temperature-sensitive in cell transformation. The amount of this protein, however, accumulated in cells infected by these temperature-sensitive mutants, relative to the structural polypeptides, differed significnatly from that seen with the nondefective virus. Pulsechase experiments indicate that the protein is extremely unstable, with a half-life of about 20 min, and does not serve as a precursor to any of the detectable virion polypeptides. Furthermore, incubation of the rat antiserum with purified, disrupted virus did not affect its immunoreactivity to this particular protein. We conclude that this 56,000 dalton molecular weight protein is a nonstructural protein specific to cells transformed by Rous sarcoma virus."}
{"id": "PMID:207436", "title": "Formation of Okazaki fragments in polyoma DNA synthesis caused by misincorporation of uracil.", "content": "When dUTP replaced dTTP during polyoma DNA replication in isolated cell nuclei, radioactivity from labeled deoxynucleoside triphosphates was almost exclusively recovered in very short Okazaki fragments and incorporation ceased after a short time. Addition of uracil, a known inhibitor of the enzyme uracil-DNA glycosidase (Lindahl et al., 1977), increased total synthesis and shifted the incorporation to longer progeny strands. The presence of as little as 2.5% of dUTP in a dTTP-containing system gave a distinct increase in isotope incorporation into Okazaki pieces accompanied by a corresponding decrease in longer strands. This effect was reversed completely by uracil. The short strands formed from dUTP could be chased efficiently into long strands. Our results suggest that dUTP can be incorporated in place of dTTP into polyoma DNA, and that polyoma-infected nuclei, similar to E. coli (Tye et al., 1977), contain an excision-repair system which by removal of uracil causes strand breakage and under certain circumstances may contribute to the formation of Okazaki fragments.", "contents": "Formation of Okazaki fragments in polyoma DNA synthesis caused by misincorporation of uracil. When dUTP replaced dTTP during polyoma DNA replication in isolated cell nuclei, radioactivity from labeled deoxynucleoside triphosphates was almost exclusively recovered in very short Okazaki fragments and incorporation ceased after a short time. Addition of uracil, a known inhibitor of the enzyme uracil-DNA glycosidase (Lindahl et al., 1977), increased total synthesis and shifted the incorporation to longer progeny strands. The presence of as little as 2.5% of dUTP in a dTTP-containing system gave a distinct increase in isotope incorporation into Okazaki pieces accompanied by a corresponding decrease in longer strands. This effect was reversed completely by uracil. The short strands formed from dUTP could be chased efficiently into long strands. Our results suggest that dUTP can be incorporated in place of dTTP into polyoma DNA, and that polyoma-infected nuclei, similar to E. coli (Tye et al., 1977), contain an excision-repair system which by removal of uracil causes strand breakage and under certain circumstances may contribute to the formation of Okazaki fragments."}
{"id": "PMID:207437", "title": "Synthesis and infectivity of vesicular stomatitis virus containing nonglycosylated G protein.", "content": "The replication of vesicular stomatitis virus (VSV) is inhibited by tunicamycin (TM), an antibiotic that blocks the formation of N-acetylglucosaminelipid intermediates. We had shown previously that the viral glycoprotein (G) synthesized in cells treated with TM is not glycosylated and is not found on the outer surface of the cell plasma membrane. In this report, we shown that cells exposed to TM produce a low yield of infectious particles. The yield is increased when the temperature during infection is lowered from 37 to 30 degrees C. At 30 degrees C in the presence of TM, both wild-type VSV and the temperature-sensitive mutant ts045 produce particles that do not bind to concanavalin A Sepharose and contain only the nonglycosylated form of G. These particles have a specific infectivity (pfu/cpm) comparable to that of VSV containing glycosylated G.", "contents": "Synthesis and infectivity of vesicular stomatitis virus containing nonglycosylated G protein. The replication of vesicular stomatitis virus (VSV) is inhibited by tunicamycin (TM), an antibiotic that blocks the formation of N-acetylglucosaminelipid intermediates. We had shown previously that the viral glycoprotein (G) synthesized in cells treated with TM is not glycosylated and is not found on the outer surface of the cell plasma membrane. In this report, we shown that cells exposed to TM produce a low yield of infectious particles. The yield is increased when the temperature during infection is lowered from 37 to 30 degrees C. At 30 degrees C in the presence of TM, both wild-type VSV and the temperature-sensitive mutant ts045 produce particles that do not bind to concanavalin A Sepharose and contain only the nonglycosylated form of G. These particles have a specific infectivity (pfu/cpm) comparable to that of VSV containing glycosylated G."}
{"id": "PMID:207438", "title": "Avian myelocytomatosis and erythroblastosis viruses lack the transforming gene src of avian sarcoma viruses.", "content": "Using labeled cDNA specific for the detection of the src gene of avian sarcoma viruses, we find that avian myelocytomatosis virus strain MC29 and avian erythroblastosis virus strain ES4 lack nucleotide sequences related to the src gene. Furthermore, chicken fibroblasts as well as hematopoietic cells, infected and transformed with these viruses, show no enhanced level of transcription of the cellular nucleotide sequences related to the src gene of avian sarcoma viruses. These two viruses may thus contain their own transforming gene(s) or induce cellular genes unrelated to the src-like cellular sequences.", "contents": "Avian myelocytomatosis and erythroblastosis viruses lack the transforming gene src of avian sarcoma viruses. Using labeled cDNA specific for the detection of the src gene of avian sarcoma viruses, we find that avian myelocytomatosis virus strain MC29 and avian erythroblastosis virus strain ES4 lack nucleotide sequences related to the src gene. Furthermore, chicken fibroblasts as well as hematopoietic cells, infected and transformed with these viruses, show no enhanced level of transcription of the cellular nucleotide sequences related to the src gene of avian sarcoma viruses. These two viruses may thus contain their own transforming gene(s) or induce cellular genes unrelated to the src-like cellular sequences."}
{"id": "PMID:207440", "title": "MAC-1, a new genetically transmitted type C virus of primates: \"low frequency\" activation from stumptail monkey cell cultures.", "content": "A new class of endogenous primate type C virus has been isolated from a continuous tissue culture line of Macaca arctoides cells by co-cultivation with a human cell line. The virus, designated MAC-1, can be transmitted to human and feline cells in tissue culture, and is unrelated, by immunological and nucleic acid hybridization criteria, to previously characterized retroviral isolates of primates. In particular, MAC-1 shows no detectable homology to the baboon type C viruses, even though viral genes related to the latter group are readily detected in M. arctoides cellular DNA. Viral gene sequences related to the MAC-1 genome are present in multiple copies (50-150 per haploid genome) in Old World primates, and are expressed in the cellular RNAs of uninfected and \"virus-free\" primate cells and tissues. Thus there are at least two distinct sets of genetically transmitted Old World primate type C viral genes, each of which is found in multiple copies in normal primate cellular DNA. With the description of this new retrovirus, there are now a minimum of five distinct genetically transmitted viruses of primates, three type C and type D, each represented in multiple copies in the normal cellular DNA.", "contents": "MAC-1, a new genetically transmitted type C virus of primates: \"low frequency\" activation from stumptail monkey cell cultures. A new class of endogenous primate type C virus has been isolated from a continuous tissue culture line of Macaca arctoides cells by co-cultivation with a human cell line. The virus, designated MAC-1, can be transmitted to human and feline cells in tissue culture, and is unrelated, by immunological and nucleic acid hybridization criteria, to previously characterized retroviral isolates of primates. In particular, MAC-1 shows no detectable homology to the baboon type C viruses, even though viral genes related to the latter group are readily detected in M. arctoides cellular DNA. Viral gene sequences related to the MAC-1 genome are present in multiple copies (50-150 per haploid genome) in Old World primates, and are expressed in the cellular RNAs of uninfected and \"virus-free\" primate cells and tissues. Thus there are at least two distinct sets of genetically transmitted Old World primate type C viral genes, each of which is found in multiple copies in normal primate cellular DNA. With the description of this new retrovirus, there are now a minimum of five distinct genetically transmitted viruses of primates, three type C and type D, each represented in multiple copies in the normal cellular DNA."}
{"id": "PMID:207441", "title": "Electron microscopic evidence for splicing of SV40 late mRNAs.", "content": "Poly(A)-containing SV40 cytoplasmic RNA was hybridized with linear double-stranded SV40 DNA and formed RNA displacement loops (R loops). The structures visualized in the electron microscope are consistent with the conclusion that the leader sequences at the 5' ends of the 16S and 19S late mRNAs are not coded immediately adjacent to the main portions of the mRNAs. These data are consistent with either segmentation of the leaders or heterogeneity of their lengths. Measurements carried out on the R loop structures have provided the locations, on the physical map of SV40 DNA, for the bodies and leaders of the 16S and 19S late mRNAs, and the lengths of the bodies, leaders and the corresponding intervening DNA sequences.", "contents": "Electron microscopic evidence for splicing of SV40 late mRNAs. Poly(A)-containing SV40 cytoplasmic RNA was hybridized with linear double-stranded SV40 DNA and formed RNA displacement loops (R loops). The structures visualized in the electron microscope are consistent with the conclusion that the leader sequences at the 5' ends of the 16S and 19S late mRNAs are not coded immediately adjacent to the main portions of the mRNAs. These data are consistent with either segmentation of the leaders or heterogeneity of their lengths. Measurements carried out on the R loop structures have provided the locations, on the physical map of SV40 DNA, for the bodies and leaders of the 16S and 19S late mRNAs, and the lengths of the bodies, leaders and the corresponding intervening DNA sequences."}
{"id": "PMID:207442", "title": "Construction of a viable SV40 variant containing two functional origins of DNA replication.", "content": "Viable variants of simian virus 40 (SV40) have been constructed which contain two functional origins of DNA replication (Or). The variants were made by introducing, at 0.175 on the SV40 map, a segment of DNA containing the viral Or. Two types of experiments demonstrate that the second Or is functional. First, the distribution of radioactivity in pulse-labeled SV40 (I) DNA is dramatically altered in the variants when compared with the parental virus. Second, electron microscopic examination of viral replicative intermediates indicates that while there is one initiation site for DNA synthesis in the parental genome, there are two sites in the variant. It was possible to introduce a deletion which inactivated the original Or at 0.67 map units in this variant. The resulting mutant could be propagated,  and its DNA replication originated at the site of the newly inserted Or.", "contents": "Construction of a viable SV40 variant containing two functional origins of DNA replication. Viable variants of simian virus 40 (SV40) have been constructed which contain two functional origins of DNA replication (Or). The variants were made by introducing, at 0.175 on the SV40 map, a segment of DNA containing the viral Or. Two types of experiments demonstrate that the second Or is functional. First, the distribution of radioactivity in pulse-labeled SV40 (I) DNA is dramatically altered in the variants when compared with the parental virus. Second, electron microscopic examination of viral replicative intermediates indicates that while there is one initiation site for DNA synthesis in the parental genome, there are two sites in the variant. It was possible to introduce a deletion which inactivated the original Or at 0.67 map units in this variant. The resulting mutant could be propagated,  and its DNA replication originated at the site of the newly inserted Or."}
{"id": "PMID:207443", "title": "Effects of BUdR on developmental functions of Dictyostelium discoideum.", "content": "The development of Dictyostelium discoideum cells, as measured by spore yield, is somewhat more sensitive to the presence of BUdR during vegetative growth than is growth itself. Observations on the development of control and BUdR-grown cells, their protein labelling patterns and assays of 4 developmentally regulated proteins all reveal a consistent picture. BUdR appears to block spore formation by partially inhibiting several or many different earlier events during development. The relative sensitivity of development compared to growth to inhibition by the drug may be a consequence of the nature of the developmental process rather than of some unique specificity of the inhibitor.", "contents": "Effects of BUdR on developmental functions of Dictyostelium discoideum. The development of Dictyostelium discoideum cells, as measured by spore yield, is somewhat more sensitive to the presence of BUdR during vegetative growth than is growth itself. Observations on the development of control and BUdR-grown cells, their protein labelling patterns and assays of 4 developmentally regulated proteins all reveal a consistent picture. BUdR appears to block spore formation by partially inhibiting several or many different earlier events during development. The relative sensitivity of development compared to growth to inhibition by the drug may be a consequence of the nature of the developmental process rather than of some unique specificity of the inhibitor."}
{"id": "PMID:207444", "title": "Resurgence of glycogen synthesis and storage capacity in cultured hepatoma cells.", "content": "This paper describes a new cultured hepatoma cell line referred as ZHC cells, derived from the ascitic Zajdela rat hepatoma. Since 1963, the dedifferenciated in vivo transplanted ascitic cells were characterized by the absence of glycogen as in generally the case in all fast growing hepatic tumors. In 1974, we succeeded in adapting these tumor cell to in vitro defined growth conditions, where we observed the progressive recovery of the ability to synthesize and to store large amounts of glycogen, as shown by histochemical, ultrastructural and biochemical studies. It can now be considered as an established cell line in which the reverted phenotype has been stable for 3 years.", "contents": "Resurgence of glycogen synthesis and storage capacity in cultured hepatoma cells. This paper describes a new cultured hepatoma cell line referred as ZHC cells, derived from the ascitic Zajdela rat hepatoma. Since 1963, the dedifferenciated in vivo transplanted ascitic cells were characterized by the absence of glycogen as in generally the case in all fast growing hepatic tumors. In 1974, we succeeded in adapting these tumor cell to in vitro defined growth conditions, where we observed the progressive recovery of the ability to synthesize and to store large amounts of glycogen, as shown by histochemical, ultrastructural and biochemical studies. It can now be considered as an established cell line in which the reverted phenotype has been stable for 3 years."}
{"id": "PMID:207445", "title": "Morphological and biochemical differentiation in RSV transformed chick embryo myoblasts.", "content": "Chick embryo myoblasts have been transformed with a temperature sensitive mutant of Rous Sarcoma virus (RSV ts68). At permissive temperature (36 degrees C) it is shown that transformed myoblasts have lost their ability to form myotubes as well as to express the biochemical markers of myogenic differentiation. Upon a shift to the non-permissive temperature (41 degrees C), the normal program of differentiation is restored; myotubes are formed which express muscle specific proteins.", "contents": "Morphological and biochemical differentiation in RSV transformed chick embryo myoblasts. Chick embryo myoblasts have been transformed with a temperature sensitive mutant of Rous Sarcoma virus (RSV ts68). At permissive temperature (36 degrees C) it is shown that transformed myoblasts have lost their ability to form myotubes as well as to express the biochemical markers of myogenic differentiation. Upon a shift to the non-permissive temperature (41 degrees C), the normal program of differentiation is restored; myotubes are formed which express muscle specific proteins."}
{"id": "PMID:207449", "title": "Importance of apolipoproteins in lipid metabolism.", "content": "Lipids, which serve as a source of energy and are an important constituent of cell membrane structure, are readily stored in the body. By definition they are insoluble in water. Specific proteins called apolipoproteins interact with lipids to form soluble lipid-protein complexes called lipoproteins. It is in this form that the major lipids--cholesterol, triglyceride and phospholipid--circulate in plasma. Unesterified fatty acids, another major lipid group, are bound to albumin in the circulation. The plasma lipoproteins are complex macromolecules composed of lipids, apolipoproteins and carbohydrates. The relative proportions of these components differ markedly between lipoprotein classes. Hyperlipidemia is a term used for increased concentrations of plasma cholesterol and/or triglycerides. Any one plasma lipid is present in several types of lipoproteins. Thus, hyperlipidemia implies the presence of hyperlipoproteinemia. The latter has important therapeutic implications. Most of the recent attempts at classification have been directed at the lipoprotein level of plasma lipid organization. Decreased concentrations of lipids in plasma can be achieved by altering the rates of metabolism of lipoproteins. Decrease in lipoprotein synthesis, increased catabolism or impaired release from cells into the blood stream may all result in a decrease of plasma lipids. Drugs which affect one or more of these factors are used to treat hyperlipoproteinemia. In order to elucidate the mechanism of action of hypolipidemic drugs it is necessary to understand the lipoprotein defect at the molecular level. This requires a more detailed knowledge of lipoprotein metabolism than is presently available for most of the hyperlipoproteinemias. This paper will review some of the generally accepted properties of the plasma lipoproteins, describe some difficulties which hamper the understanding of lipoprotein metabolism, and identify possible mechanisms by which drugs may affect lipoprotein metabolism.", "contents": "Importance of apolipoproteins in lipid metabolism. Lipids, which serve as a source of energy and are an important constituent of cell membrane structure, are readily stored in the body. By definition they are insoluble in water. Specific proteins called apolipoproteins interact with lipids to form soluble lipid-protein complexes called lipoproteins. It is in this form that the major lipids--cholesterol, triglyceride and phospholipid--circulate in plasma. Unesterified fatty acids, another major lipid group, are bound to albumin in the circulation. The plasma lipoproteins are complex macromolecules composed of lipids, apolipoproteins and carbohydrates. The relative proportions of these components differ markedly between lipoprotein classes. Hyperlipidemia is a term used for increased concentrations of plasma cholesterol and/or triglycerides. Any one plasma lipid is present in several types of lipoproteins. Thus, hyperlipidemia implies the presence of hyperlipoproteinemia. The latter has important therapeutic implications. Most of the recent attempts at classification have been directed at the lipoprotein level of plasma lipid organization. Decreased concentrations of lipids in plasma can be achieved by altering the rates of metabolism of lipoproteins. Decrease in lipoprotein synthesis, increased catabolism or impaired release from cells into the blood stream may all result in a decrease of plasma lipids. Drugs which affect one or more of these factors are used to treat hyperlipoproteinemia. In order to elucidate the mechanism of action of hypolipidemic drugs it is necessary to understand the lipoprotein defect at the molecular level. This requires a more detailed knowledge of lipoprotein metabolism than is presently available for most of the hyperlipoproteinemias. This paper will review some of the generally accepted properties of the plasma lipoproteins, describe some difficulties which hamper the understanding of lipoprotein metabolism, and identify possible mechanisms by which drugs may affect lipoprotein metabolism."}
{"id": "PMID:207450", "title": "Cytochrome P-450 distribution in rat liver and the effect of sodium phenobarbitone administration.", "content": "A microspectrophotometric method for assaying cytochrome P-450 in fresh 24 micrometer unfixed cryostat sections of rat liver has been developed. When used to assay this cytochrome in sections of microsomal preparations it has yielded results equivalent to those obtained by the conventional spectrophotometric assay of the same preparations. Random measurements made throughout sections of liver have given mean values for cytochrome P-450 concentrations which are twice those measured in microsomes prepared from the livers of the same animals (not corrected for the yield in the homogenate). Measurements of the cytochrome P-450 content of liver cells by the microspectrophotometric method show that in liver from male Wistar rats, cells nearer to the central veins contain up to twice as much cytochrome P-450 as those nearer to the portal tract (mean cell concentrations of 26.4 (+/-4.4) mumol/l and 17.5 (+/-3.0) mumol/l respectively). In the livers from similar rats, killed at the same time, but which has received 1 mg/ml sodium phenobarbitone in their drinking water for one week, the cells near the central vein contained up to five times as much cytochrome P-450 as those near the portal tract (mean cell concentrations of 77.3 (+/-25.0) mumol/l and 28.3 (+/-9.6) mumol/l respectively). The results show a selective increase in cytochrome P-450 content by the cells in the centrilobular region after treatment with sodium phenobarbitone and a smaller increase by some of the cells in the periportal region.", "contents": "Cytochrome P-450 distribution in rat liver and the effect of sodium phenobarbitone administration. A microspectrophotometric method for assaying cytochrome P-450 in fresh 24 micrometer unfixed cryostat sections of rat liver has been developed. When used to assay this cytochrome in sections of microsomal preparations it has yielded results equivalent to those obtained by the conventional spectrophotometric assay of the same preparations. Random measurements made throughout sections of liver have given mean values for cytochrome P-450 concentrations which are twice those measured in microsomes prepared from the livers of the same animals (not corrected for the yield in the homogenate). Measurements of the cytochrome P-450 content of liver cells by the microspectrophotometric method show that in liver from male Wistar rats, cells nearer to the central veins contain up to twice as much cytochrome P-450 as those nearer to the portal tract (mean cell concentrations of 26.4 (+/-4.4) mumol/l and 17.5 (+/-3.0) mumol/l respectively). In the livers from similar rats, killed at the same time, but which has received 1 mg/ml sodium phenobarbitone in their drinking water for one week, the cells near the central vein contained up to five times as much cytochrome P-450 as those near the portal tract (mean cell concentrations of 77.3 (+/-25.0) mumol/l and 28.3 (+/-9.6) mumol/l respectively). The results show a selective increase in cytochrome P-450 content by the cells in the centrilobular region after treatment with sodium phenobarbitone and a smaller increase by some of the cells in the periportal region."}
{"id": "PMID:207451", "title": "The association between mutagenicity and adduct formation of 1,2,7,8-diepoxyoctane and 1,2,5,6-diepoxycyclooctane.", "content": "The mutagenicity of 1,2,5,6-diepoxycyclooctane (DECO) and 1,2,7,8-diepoxyoctane (DEO) was investigated using diploid Chinese hamster lung cells. 6-thioguanine (6-TG) resistance was used as the marker for mutagenicity testing: DEO was found to be genetically active; DECO, on the contrary, totally inactive. DEO readily formed adducts with radiolabeled nucleotides, while DECO failed to do so, as demonstrated through thin-layer chromatography (TLC) and the shift of the ultraviolet absorption maximum in DEO/nucleotide mixtures. The difference between the two compounds in chemical and genetic activities was attributed to their molecular conformations and the resulting differential flexibilities and adduct-forming abilities. Association between mutagenicity and adduct formation was conclusive.", "contents": "The association between mutagenicity and adduct formation of 1,2,7,8-diepoxyoctane and 1,2,5,6-diepoxycyclooctane. The mutagenicity of 1,2,5,6-diepoxycyclooctane (DECO) and 1,2,7,8-diepoxyoctane (DEO) was investigated using diploid Chinese hamster lung cells. 6-thioguanine (6-TG) resistance was used as the marker for mutagenicity testing: DEO was found to be genetically active; DECO, on the contrary, totally inactive. DEO readily formed adducts with radiolabeled nucleotides, while DECO failed to do so, as demonstrated through thin-layer chromatography (TLC) and the shift of the ultraviolet absorption maximum in DEO/nucleotide mixtures. The difference between the two compounds in chemical and genetic activities was attributed to their molecular conformations and the resulting differential flexibilities and adduct-forming abilities. Association between mutagenicity and adduct formation was conclusive."}
{"id": "PMID:207456", "title": "[Evidence for a Na+/NH4+ exchange in the gill of trout adapted to sea water: adrenergic control].", "content": "A Na+/NH4+ exchange similar to that characterizing the fish gill in fresh water was shown to function in the trout adapted to sea water with the help of the head perfusion technique. This exchange stimulated by adrenaline through beta adrenoreceptors and inhibited by amiloride added to the external medium.", "contents": "[Evidence for a Na+/NH4+ exchange in the gill of trout adapted to sea water: adrenergic control]. A Na+/NH4+ exchange similar to that characterizing the fish gill in fresh water was shown to function in the trout adapted to sea water with the help of the head perfusion technique. This exchange stimulated by adrenaline through beta adrenoreceptors and inhibited by amiloride added to the external medium."}
{"id": "PMID:207457", "title": "[Use of Cowan strain I of Staphylococcus aureus for radio-immunological determination of retrovirus proteins].", "content": "The use of Staphylococcus aureus for the radio-immunoassay of C-type virus polypeptides provided very specific results and proved to present several advantages over the classical methods of precipitation of immune complexes.", "contents": "[Use of Cowan strain I of Staphylococcus aureus for radio-immunological determination of retrovirus proteins]. The use of Staphylococcus aureus for the radio-immunoassay of C-type virus polypeptides provided very specific results and proved to present several advantages over the classical methods of precipitation of immune complexes."}
{"id": "PMID:207459", "title": "Effects of substrates on tissue metabolic changes in the isolated rat heart during underperfusion and on release of lactate dehydrogenase and arrhythmias during reperfusion.", "content": "In Langendorff-perfused rat hearts, the perfusion pressure was reduced from 100 cm H2O to 20 cm H2O for 30 minutes to produce a model of global ischemia with a residual oxygen uptake. The release of lactate dehydrogenase (LDH) and the occurrence of ventricular arrhythmias during reperfusion were dependent on the substrate. Glucose-perfused hearts had the highest rates of glycolytic ATP production (2.5 mumol/g per min) during ischemia with normal contents of tissue cyclic adenosine 3',5'-monophosphate (cAMP) and, during reperfusion, the release of LDH was lowest and severe ventricular arrhythmias did not occur. In pyruvate-perfused hearts, glycolysis was inhibited during ischemia, the rate of production of glycolytic ATP was only 0.5 mumol/g per min. and tissue cAMP doubled; during reperfusion, LDH release was 14-fold higher and ventricular arrhythmias were more severe. Total tissue contents of ATP and phosphocreatine were similar in glucose- and in pyruvate-perfused hearts. In hearts perfused with acetate, there was virtually no glycolytic ATP synthesized during the last 5 minutes of ischemia and cAMP increased further. Acetate-  and palmitate-perfused hearts showed greatest release of LDH and had severest arrhythmias during reperfusion, suggesting that it was the metabolic and not the detergent effects of palmitate that were operating. Lipolysis was not a major factor in the cause of reperfusion LDH release. A role of glycolytic ATP in the maintenance of membrane integrity is postulated.", "contents": "Effects of substrates on tissue metabolic changes in the isolated rat heart during underperfusion and on release of lactate dehydrogenase and arrhythmias during reperfusion. In Langendorff-perfused rat hearts, the perfusion pressure was reduced from 100 cm H2O to 20 cm H2O for 30 minutes to produce a model of global ischemia with a residual oxygen uptake. The release of lactate dehydrogenase (LDH) and the occurrence of ventricular arrhythmias during reperfusion were dependent on the substrate. Glucose-perfused hearts had the highest rates of glycolytic ATP production (2.5 mumol/g per min) during ischemia with normal contents of tissue cyclic adenosine 3',5'-monophosphate (cAMP) and, during reperfusion, the release of LDH was lowest and severe ventricular arrhythmias did not occur. In pyruvate-perfused hearts, glycolysis was inhibited during ischemia, the rate of production of glycolytic ATP was only 0.5 mumol/g per min. and tissue cAMP doubled; during reperfusion, LDH release was 14-fold higher and ventricular arrhythmias were more severe. Total tissue contents of ATP and phosphocreatine were similar in glucose- and in pyruvate-perfused hearts. In hearts perfused with acetate, there was virtually no glycolytic ATP synthesized during the last 5 minutes of ischemia and cAMP increased further. Acetate-  and palmitate-perfused hearts showed greatest release of LDH and had severest arrhythmias during reperfusion, suggesting that it was the metabolic and not the detergent effects of palmitate that were operating. Lipolysis was not a major factor in the cause of reperfusion LDH release. A role of glycolytic ATP in the maintenance of membrane integrity is postulated."}
{"id": "PMID:207461", "title": "Multi-laboratory comparison of three heparin-Mn2+ precipitation procedures for estimating cholesterol in high-density lipoprotein.", "content": "Plasma high-density lipoprotein is commonly estimated by measuring the cholesterol remaining in plasma supernatant solutions after other lipoproteins, which contain apolipoprotein B, are precipitated with heparin and Mn2+. The method (method I) now in use by the Lipid Research Clinics, in which Mn2+ is at 46 mmol/liter final concentration, is reasonably accurate, but precipitation and sedimentation of lipoproteins other than high-density lipoproteins is often incomplete. We evaluated two modifications of method I. In method II, the Mn2+ concentration was doubled; the second modification (method III) included the increased Mn2+ concentration in a combined heparin Mn2+ reagent, decreased sample volume (2 ml), and a shorter incubation time (10 min at room temperature). The percentages of samples with turbid supernates (i.e., incomplete sedimentation) by methods I, II, and III were 9, 3, and 2%, respectively. Among non-turbid supernates, the percentages of samples containing measurable apolipoprotein B (incomplete precipitation) were 79, 19, and 16%, respectively. We conclude that method III is the most convenient and accurate of the three procedures.", "contents": "Multi-laboratory comparison of three heparin-Mn2+ precipitation procedures for estimating cholesterol in high-density lipoprotein. Plasma high-density lipoprotein is commonly estimated by measuring the cholesterol remaining in plasma supernatant solutions after other lipoproteins, which contain apolipoprotein B, are precipitated with heparin and Mn2+. The method (method I) now in use by the Lipid Research Clinics, in which Mn2+ is at 46 mmol/liter final concentration, is reasonably accurate, but precipitation and sedimentation of lipoproteins other than high-density lipoproteins is often incomplete. We evaluated two modifications of method I. In method II, the Mn2+ concentration was doubled; the second modification (method III) included the increased Mn2+ concentration in a combined heparin Mn2+ reagent, decreased sample volume (2 ml), and a shorter incubation time (10 min at room temperature). The percentages of samples with turbid supernates (i.e., incomplete sedimentation) by methods I, II, and III were 9, 3, and 2%, respectively. Among non-turbid supernates, the percentages of samples containing measurable apolipoprotein B (incomplete precipitation) were 79, 19, and 16%, respectively. We conclude that method III is the most convenient and accurate of the three procedures."}
{"id": "PMID:207462", "title": "Heparin--Mn2+ quantitation of high-density-lipoprotein cholesterol: an ultrafiltration procedure for lipemic samples.", "content": "We describe a modified heparin--Mn2+ procedure for high-density-lipoprotein cholesterol quantitation, especially in lipemic samples. High-density-lipoproteins may be estimated as cholesterol remaining in plasma supernates after precipitation of other lipoproteins by heparin and Mn2+ treatment. However, in lipemic samples or those from non-fasting individuals, the lower density of the precipitated chylomicrons, very-low-, and low-density-lipoproteins frequently prevents their sedimentation by the usual low-speed centrifugation, and high-density-lipoprotein cholesterol thus is overestimated in the resulting turbid supernates. Sedimentation is improved by a twofold increase in Mn2+ concentration to 92 mmol/liter. The procedure reported here produced clear supernates in more than 95% of samples tested. Any remaining turbid supernates can be cleared by a simple, convenient ultrafiltration technique. The filtration removed essentially all of the very-low- and low-density-lipoproteins without removing appreciable amounts of high-density-lipoproteins.", "contents": "Heparin--Mn2+ quantitation of high-density-lipoprotein cholesterol: an ultrafiltration procedure for lipemic samples. We describe a modified heparin--Mn2+ procedure for high-density-lipoprotein cholesterol quantitation, especially in lipemic samples. High-density-lipoproteins may be estimated as cholesterol remaining in plasma supernates after precipitation of other lipoproteins by heparin and Mn2+ treatment. However, in lipemic samples or those from non-fasting individuals, the lower density of the precipitated chylomicrons, very-low-, and low-density-lipoproteins frequently prevents their sedimentation by the usual low-speed centrifugation, and high-density-lipoprotein cholesterol thus is overestimated in the resulting turbid supernates. Sedimentation is improved by a twofold increase in Mn2+ concentration to 92 mmol/liter. The procedure reported here produced clear supernates in more than 95% of samples tested. Any remaining turbid supernates can be cleared by a simple, convenient ultrafiltration technique. The filtration removed essentially all of the very-low- and low-density-lipoproteins without removing appreciable amounts of high-density-lipoproteins."}
{"id": "PMID:207463", "title": "Cholesterol in high-density lipoprotein: use of Mg2+/dextran sulfate in its enzymic measurement.", "content": "We describe a method for measuring high-density lipoprotein cholesterol. MgCl2 and dextran sulfate are used to precipitate all low-density and very-low-density lipoproteins. The supernate contains only high-density lipoproteins, the cholesterol concentration of which is estimated by an enzymic method, with a discrete analyzer (Abbott Bichromatic Analyzer). Concentration and instrument response are linearly related to 50 mg/liter. The precision of the method is excellent in the range of clinical interest (100 to 1000 mg of cholesterol per liter). The precision and efficiency of the precipitation are shown at various concentrations of high-density lipoprotein cholesterol. The method was compared to that of two laboratories in the Cooperative Lipoprotein Phenotyping Study group by testing a number of split samples, and agreement was good.", "contents": "Cholesterol in high-density lipoprotein: use of Mg2+/dextran sulfate in its enzymic measurement. We describe a method for measuring high-density lipoprotein cholesterol. MgCl2 and dextran sulfate are used to precipitate all low-density and very-low-density lipoproteins. The supernate contains only high-density lipoproteins, the cholesterol concentration of which is estimated by an enzymic method, with a discrete analyzer (Abbott Bichromatic Analyzer). Concentration and instrument response are linearly related to 50 mg/liter. The precision of the method is excellent in the range of clinical interest (100 to 1000 mg of cholesterol per liter). The precision and efficiency of the precipitation are shown at various concentrations of high-density lipoprotein cholesterol. The method was compared to that of two laboratories in the Cooperative Lipoprotein Phenotyping Study group by testing a number of split samples, and agreement was good."}
{"id": "PMID:207464", "title": "Biochemical properties of tartrate-resistant acid phosphatase in serum of adults and children.", "content": "Spectrophotometry of total acid phosphatase activity in children's sera showed an average value of 22.4 +/- 2.9 and 7.4 +/- 0.8 U/liter, for the hydrolysis of p-nitrophenyl phosphate and alpha-naphthyl phosphate, respectively. Analyses of \"band 5b\", after electrophoresis on acrylamide gel, gave even higher values. The values for children's sera were much higher than those for sera from adults. The multiplicity of acid phosphatases in sera of children and adults was studied by electrophoresis on acrylamide gel and by chromatography on CM-Sepharose. Both methods showed the major acid phosphatase in children's sera to be an acid pyrophosphatase, band 5b. Its catalytic properties are indistinguishable from the enzyme previously isolated from the spleen of leukemic reticuloendotheliosis.", "contents": "Biochemical properties of tartrate-resistant acid phosphatase in serum of adults and children. Spectrophotometry of total acid phosphatase activity in children's sera showed an average value of 22.4 +/- 2.9 and 7.4 +/- 0.8 U/liter, for the hydrolysis of p-nitrophenyl phosphate and alpha-naphthyl phosphate, respectively. Analyses of \"band 5b\", after electrophoresis on acrylamide gel, gave even higher values. The values for children's sera were much higher than those for sera from adults. The multiplicity of acid phosphatases in sera of children and adults was studied by electrophoresis on acrylamide gel and by chromatography on CM-Sepharose. Both methods showed the major acid phosphatase in children's sera to be an acid pyrophosphatase, band 5b. Its catalytic properties are indistinguishable from the enzyme previously isolated from the spleen of leukemic reticuloendotheliosis."}
{"id": "PMID:207466", "title": "Enzymic determination of cholesterol in serum lipoproteins separated by electrophoresis.", "content": "We describe a reliable, straightforward procedure for measuring the cholesterol content of serum lipoproteins separated by electrophoresis on cellulose acetate. The lipoprotein fractions are made visible by use of an enzymic reagent and then quantitated by densitometry. Standard electrophoresis equipment is used and the procedure requires just over 1 h for completion. All major fractions except chylomicrons are detected readily. Accuracy and precision agree favorably with results reported for generally accepted methods. Concentration and color development are linearly related to cholesterol concentrations up to 1.5 g/liter in a given lipoprotein fraction. We recommend this method for use in assessing high-density lipoprotein cholesterol and as an aid in lipoprotein phenotyping.", "contents": "Enzymic determination of cholesterol in serum lipoproteins separated by electrophoresis. We describe a reliable, straightforward procedure for measuring the cholesterol content of serum lipoproteins separated by electrophoresis on cellulose acetate. The lipoprotein fractions are made visible by use of an enzymic reagent and then quantitated by densitometry. Standard electrophoresis equipment is used and the procedure requires just over 1 h for completion. All major fractions except chylomicrons are detected readily. Accuracy and precision agree favorably with results reported for generally accepted methods. Concentration and color development are linearly related to cholesterol concentrations up to 1.5 g/liter in a given lipoprotein fraction. We recommend this method for use in assessing high-density lipoprotein cholesterol and as an aid in lipoprotein phenotyping."}
{"id": "PMID:207467", "title": "Laboratory standardizatin in an international study: the Kaunas--Rotterdam intervention study (KRIS).", "content": "Laboratory results obtained in different laboratories over lengthy periods of time usually are difficult to compare. In cooperative long-term studies where such results must be pooled, thorough standardization of methods is vital. We describe a program in which comparable plasma cholesterol and glucose analyses have been obtained, by simple methods. In the Netherlands and the Soviet Union in close collaboration with the Center for Disease Control, Atlanta, Ga., U.S.A. The two laboratories produced glucose values (direct o-toluidine reaction) within 2% of the target reference values and cholesterol results (direct Liebermann-Burchard reaction) with a consistent 6-8% positive bias over the reference method values. Intralaboratory precision was subject to preset acceptance limits. The use of common control materials, exchange of patient samples, and on-site comparison of all details of laboratory procedures are vital tools in standardization efforts. A laboratory protocol that included quality requirements and rejection criteria was developed and proved to be indispensable. The experience gained should be useful in standardizing inter-laboratory results in similar studies.", "contents": "Laboratory standardizatin in an international study: the Kaunas--Rotterdam intervention study (KRIS). Laboratory results obtained in different laboratories over lengthy periods of time usually are difficult to compare. In cooperative long-term studies where such results must be pooled, thorough standardization of methods is vital. We describe a program in which comparable plasma cholesterol and glucose analyses have been obtained, by simple methods. In the Netherlands and the Soviet Union in close collaboration with the Center for Disease Control, Atlanta, Ga., U.S.A. The two laboratories produced glucose values (direct o-toluidine reaction) within 2% of the target reference values and cholesterol results (direct Liebermann-Burchard reaction) with a consistent 6-8% positive bias over the reference method values. Intralaboratory precision was subject to preset acceptance limits. The use of common control materials, exchange of patient samples, and on-site comparison of all details of laboratory procedures are vital tools in standardization efforts. A laboratory protocol that included quality requirements and rejection criteria was developed and proved to be indispensable. The experience gained should be useful in standardizing inter-laboratory results in similar studies."}
{"id": "PMID:207468", "title": "Marked hyperamylasemia associated with carcinoma of the lung.", "content": "We present a case of marked hyperamylasemia associated with undifferentiated small cell carcinoma of the lung. The serum alpha-amylase had an electrophoretic mobility similar to that of salivary gland enzyme (s-type), and that in tissue extracts from the lung tumor and metastatic skin nodules showed similar migration. No evidence of a salivary or pancreatic cause of hyperamylasemia was found at autopsy, and macroamylasemia was excluded. We suggest that the strikingly increased serum alpha-amylase activity was a result of ectopic production of this enzyme by tumor. We compare results for this case to other published reports.", "contents": "Marked hyperamylasemia associated with carcinoma of the lung. We present a case of marked hyperamylasemia associated with undifferentiated small cell carcinoma of the lung. The serum alpha-amylase had an electrophoretic mobility similar to that of salivary gland enzyme (s-type), and that in tissue extracts from the lung tumor and metastatic skin nodules showed similar migration. No evidence of a salivary or pancreatic cause of hyperamylasemia was found at autopsy, and macroamylasemia was excluded. We suggest that the strikingly increased serum alpha-amylase activity was a result of ectopic production of this enzyme by tumor. We compare results for this case to other published reports."}
{"id": "PMID:207470", "title": "Formation of vitamin D metabolites from 3H- and 14C-radiolabelled vitamin D-3 in chronic liver diseases.", "content": "Four of the eight patients studied were vitamin D replete and 4 vitamin D depleted as judged by serum 25-hydroxy vitamin D (25-OHD) concentration. Three of the 4 vitamin D depleted patients (including 2 with histological osteomalacia) formed radioactive 1,25-dihydroxycholecalciferol. One of the four vitamin D replete patients formed 1,25-dihydroxycholecalciferol but all formed 24,25-dihydroxycholecalciferol. This study suggests that patients with liver disease form dihydroxy vitamin D metabolites in an appropriate manner.", "contents": "Formation of vitamin D metabolites from 3H- and 14C-radiolabelled vitamin D-3 in chronic liver diseases. Four of the eight patients studied were vitamin D replete and 4 vitamin D depleted as judged by serum 25-hydroxy vitamin D (25-OHD) concentration. Three of the 4 vitamin D depleted patients (including 2 with histological osteomalacia) formed radioactive 1,25-dihydroxycholecalciferol. One of the four vitamin D replete patients formed 1,25-dihydroxycholecalciferol but all formed 24,25-dihydroxycholecalciferol. This study suggests that patients with liver disease form dihydroxy vitamin D metabolites in an appropriate manner."}
{"id": "PMID:207471", "title": "Selective precipitation of very low density lipoproteins from fasting sera by heparin and manganese ions.", "content": "Complete and discrete precipitation of very low density lipoproteins (VLDL) from fasting sera required heating at 40 degrees C for 60 min in the presence of 0.05 M manganous ions and heparin in a concentration dependent upon the VLDL content. The minimum polyanion concentration, employed with VLDL contents less than 1.0 g/l, was 85 mg/l; an increment of 5 mg/l was required for each 1.0 g/l increase in VLDL content. The products isolated by this procedure had electrophoretic, immunochemical and ultracentrifugal characteristics skin to those of native VLDL and were slightly contaminated with albumin. The reaction conditions did not affect adversely the subsequent precipitation of low density lipoproteins.", "contents": "Selective precipitation of very low density lipoproteins from fasting sera by heparin and manganese ions. Complete and discrete precipitation of very low density lipoproteins (VLDL) from fasting sera required heating at 40 degrees C for 60 min in the presence of 0.05 M manganous ions and heparin in a concentration dependent upon the VLDL content. The minimum polyanion concentration, employed with VLDL contents less than 1.0 g/l, was 85 mg/l; an increment of 5 mg/l was required for each 1.0 g/l increase in VLDL content. The products isolated by this procedure had electrophoretic, immunochemical and ultracentrifugal characteristics skin to those of native VLDL and were slightly contaminated with albumin. The reaction conditions did not affect adversely the subsequent precipitation of low density lipoproteins."}
{"id": "PMID:207472", "title": "Prenatal diagnosis of Gaucher's and Niemann-Pick diseases. Assays of glucocerebrosidase and sphingomyelinase in tissue cultures using natural substrates.", "content": "Prenatal diagnosis has been successfully achieved by enzyme assays in cultured amniocytes in three high risk pregnancies for Gaucher's disease and three for Niemann-Pick disease type A. [14C]Stearic acid glucocerebroside and [3H]-dihydrosphingomyelin were used as substrates for glucocerebrosidase and sphingomyelinase activity measurements, respectively. Values for the above two enzyme levels in cultured amniotic fluid cells of normal controls and in the pregnancies at risk are presented. The diagnosis made in utero in one fetus affected with Niemann-Pick disease was subsequently confirmed following abortion (at 19 weeks gestation), by the specific biochemical and pathological features of various organs of the afflicted fetus (to be published). Confirmation of diagnoses made in utero for heterozygous and healthy fetuses was obtained by post-partum examination of glucocerebrosidase and spingomyelinase activity levels in leukocytes of the appropriate infants.", "contents": "Prenatal diagnosis of Gaucher's and Niemann-Pick diseases. Assays of glucocerebrosidase and sphingomyelinase in tissue cultures using natural substrates. Prenatal diagnosis has been successfully achieved by enzyme assays in cultured amniocytes in three high risk pregnancies for Gaucher's disease and three for Niemann-Pick disease type A. [14C]Stearic acid glucocerebroside and [3H]-dihydrosphingomyelin were used as substrates for glucocerebrosidase and sphingomyelinase activity measurements, respectively. Values for the above two enzyme levels in cultured amniotic fluid cells of normal controls and in the pregnancies at risk are presented. The diagnosis made in utero in one fetus affected with Niemann-Pick disease was subsequently confirmed following abortion (at 19 weeks gestation), by the specific biochemical and pathological features of various organs of the afflicted fetus (to be published). Confirmation of diagnoses made in utero for heterozygous and healthy fetuses was obtained by post-partum examination of glucocerebrosidase and spingomyelinase activity levels in leukocytes of the appropriate infants."}
{"id": "PMID:207473", "title": "Urinary cyclic nucleotides in adult male cystic fibrosis patients.", "content": "Urinary adenosine 3':5' (cyclic) monophosphate and guanosine 3':5' (cyclic)-monophosphate excretion are significantly elevated in adult male cystic fibrosis patients compared to normal men when values are expressed in ways which consider the smaller size of the cystic fibrosis subjects of the same age. Cystic fibrosis patients excreted 3.22 +/- 1.16 nmol adenosine 3':5' (cyclic)monophosphate/g creatinine per 24 h vs. 1.97 +/- 0.43 for normal men (p less than 0.02); and cystic fibrosis patients excreted 0.50 +/- 0.16 nmol guanosine 3':k' (cyclic)monophosphate/g creatinine per 24 h vs. 0.30 +/- 0.07 for normal men (p less than 0.05). Subjects were all adults who had completed linear growth and sexual development, thus eliminating any possible effects of slower maturation of cystic fibrosis patients, and all subjects were male, thus avoiding the fluctuation of urinary cyclic nucleotides with the menstrual cycle, problems which had complicated interpretation of previous studies.", "contents": "Urinary cyclic nucleotides in adult male cystic fibrosis patients. Urinary adenosine 3':5' (cyclic) monophosphate and guanosine 3':5' (cyclic)-monophosphate excretion are significantly elevated in adult male cystic fibrosis patients compared to normal men when values are expressed in ways which consider the smaller size of the cystic fibrosis subjects of the same age. Cystic fibrosis patients excreted 3.22 +/- 1.16 nmol adenosine 3':5' (cyclic)monophosphate/g creatinine per 24 h vs. 1.97 +/- 0.43 for normal men (p less than 0.02); and cystic fibrosis patients excreted 0.50 +/- 0.16 nmol guanosine 3':k' (cyclic)monophosphate/g creatinine per 24 h vs. 0.30 +/- 0.07 for normal men (p less than 0.05). Subjects were all adults who had completed linear growth and sexual development, thus eliminating any possible effects of slower maturation of cystic fibrosis patients, and all subjects were male, thus avoiding the fluctuation of urinary cyclic nucleotides with the menstrual cycle, problems which had complicated interpretation of previous studies."}
{"id": "PMID:207475", "title": "Modification of lymphocyte responsiveness in vitro by lambda carrageenan compared with colloidal silica and depletion of surface adherent cells.", "content": "The effects of the immunosuppressive sulphated polygalactan lambda carrageenan on in vitro models of allograft immunity were compared with the effects of removing macrophages (surface adherent and/or phagocytic cells) by established methods. Carrageenan depressed the primary mixed lymphocyte reactions, but not to the same extent as the removal of macrophages. 2-Mercaptoethanol restored the response. Secondary mixed lymphocyte reactions and responses to phytohaemaglutinin were depressed by carrageenan but not by the removal of macrophages, and in these systems 2-mercaptoethanol failed to restore the responses of carrageenan-treated cultures. In contrast, cell-mediated cytolysis by presensitized lymphocytes was not affected by carrageenan or by colloidal silica. Carrageenan depressed cell-mediated cytolysis only if it was present during the sensitization of the effector cells. We conclude that carrageenan can have two dose-related effects in vitro: one on the macrophage and one on the responding lymphocyte.", "contents": "Modification of lymphocyte responsiveness in vitro by lambda carrageenan compared with colloidal silica and depletion of surface adherent cells. The effects of the immunosuppressive sulphated polygalactan lambda carrageenan on in vitro models of allograft immunity were compared with the effects of removing macrophages (surface adherent and/or phagocytic cells) by established methods. Carrageenan depressed the primary mixed lymphocyte reactions, but not to the same extent as the removal of macrophages. 2-Mercaptoethanol restored the response. Secondary mixed lymphocyte reactions and responses to phytohaemaglutinin were depressed by carrageenan but not by the removal of macrophages, and in these systems 2-mercaptoethanol failed to restore the responses of carrageenan-treated cultures. In contrast, cell-mediated cytolysis by presensitized lymphocytes was not affected by carrageenan or by colloidal silica. Carrageenan depressed cell-mediated cytolysis only if it was present during the sensitization of the effector cells. We conclude that carrageenan can have two dose-related effects in vitro: one on the macrophage and one on the responding lymphocyte."}
{"id": "PMID:207481", "title": "99MTc-metyhlene diphosphonate concentration in soft tissue malignant fibrous histiocytoma.", "content": "Four cases of non-calcifying soft tissue malignant fibrous histiocytoma are presented which showed concentration of 99mTc-methylene diphosphonate. Angiography was performed in one of the patients and it featured hypervascularity, tumor staining and early draining veins indicative of arteriovenous shunting. As with other extraskeletal non-calcifying entities which exhibit enhanced uptake of 99mTc-phosphate complex, the mechanism of concentration is largely conjectural. Malignant fibrous histiocytoma can be added to the expanding list of conditions which may portray in avidity for 99mTc-phosphate complex.", "contents": "99MTc-metyhlene diphosphonate concentration in soft tissue malignant fibrous histiocytoma. Four cases of non-calcifying soft tissue malignant fibrous histiocytoma are presented which showed concentration of 99mTc-methylene diphosphonate. Angiography was performed in one of the patients and it featured hypervascularity, tumor staining and early draining veins indicative of arteriovenous shunting. As with other extraskeletal non-calcifying entities which exhibit enhanced uptake of 99mTc-phosphate complex, the mechanism of concentration is largely conjectural. Malignant fibrous histiocytoma can be added to the expanding list of conditions which may portray in avidity for 99mTc-phosphate complex."}
{"id": "PMID:207477", "title": "Hexoprenaline: beta-adrenoreceptor selectivity in isolated tissues from the guinea-pig.", "content": "1. A catecholamine beta-adrenoreceptor agonist, hexoprenaline, was examined in vitro on five guinea-pig tissues and its potency relative to isoprenaline (as 100) obtained. 2. Hexoprenaline clearly delineated between those tissues classified as containing beta2-adrenoreceptors (trachea, hind limb blood vessels and uterus; relative potencies 219, 110 and 76 respectively) and those classified as containing beta1-adrenoreceptors (atria and ileum; relative potencies 3.3 and 1.0 respectively). 3. Hexoprenaline differed from some previously studied noncatecholamine beta-adrenoreceptor agonists in being only two-fold less potent, relative to isoprenaline, as a vasodilator in perfused hind limb than as a tracheal relaxant.", "contents": "Hexoprenaline: beta-adrenoreceptor selectivity in isolated tissues from the guinea-pig. 1. A catecholamine beta-adrenoreceptor agonist, hexoprenaline, was examined in vitro on five guinea-pig tissues and its potency relative to isoprenaline (as 100) obtained. 2. Hexoprenaline clearly delineated between those tissues classified as containing beta2-adrenoreceptors (trachea, hind limb blood vessels and uterus; relative potencies 219, 110 and 76 respectively) and those classified as containing beta1-adrenoreceptors (atria and ileum; relative potencies 3.3 and 1.0 respectively). 3. Hexoprenaline differed from some previously studied noncatecholamine beta-adrenoreceptor agonists in being only two-fold less potent, relative to isoprenaline, as a vasodilator in perfused hind limb than as a tracheal relaxant."}
{"id": "PMID:207480", "title": "Spine deformities and cystic fibrosis.", "content": "Patients with cystic fibrosis have an increased risk for developing kyphosis and scoliosis. The risk for both kyphosis and scoliosis increases with age. The severity of kyphosis did not appear greater in the older age groups. Patients with retarded bone age may be more likely to have a significant spinal deformity. The presence of spine deformity does not correlate with the severity of pulmonary involvement, height, weight, serum protein and albumin in patients with cystic fibrosis.", "contents": "Spine deformities and cystic fibrosis. Patients with cystic fibrosis have an increased risk for developing kyphosis and scoliosis. The risk for both kyphosis and scoliosis increases with age. The severity of kyphosis did not appear greater in the older age groups. Patients with retarded bone age may be more likely to have a significant spinal deformity. The presence of spine deformity does not correlate with the severity of pulmonary involvement, height, weight, serum protein and albumin in patients with cystic fibrosis."}
{"id": "PMID:207490", "title": "Cutaneous manifestations of pancreatic diseases.", "content": "An awareness of the cutaneous signs of diseases of the pancreas is extremely valuable. They alert the astute examiner to several life-threatening problems that result from both benign and malignant islet cell tumors, adenocarcinomas of the pancreas, and pancreatic endocrine and inflammatory diseases. Many of the cutaneous manifestations of pancreatic disease are discussed in detail, with emphasis on both the clinical presentation and pathogenesis.", "contents": "Cutaneous manifestations of pancreatic diseases. An awareness of the cutaneous signs of diseases of the pancreas is extremely valuable. They alert the astute examiner to several life-threatening problems that result from both benign and malignant islet cell tumors, adenocarcinomas of the pancreas, and pancreatic endocrine and inflammatory diseases. Many of the cutaneous manifestations of pancreatic disease are discussed in detail, with emphasis on both the clinical presentation and pathogenesis."}
{"id": "PMID:207491", "title": "Porphyria cutanea tarda. A rare cutaneous manifestation of hepatic tumors.", "content": "Porphyria cutanea tarda (PCT), the most common form of porphyria, may be one of the rare cutaneous manifestations of hepatic tumors, benign, malignant, or metastatic. The liver damage associated with PCT may predispose to the development of hepatocellular carcinoma. Our experience and a review of the literature suggest that in patients with PCT in whom the usual precipitating factors are absent, or in patients with PCT of long duration and an unexplained exacerbation, liver scan is indicated to rule out the presence of a hepatic tumor.", "contents": "Porphyria cutanea tarda. A rare cutaneous manifestation of hepatic tumors. Porphyria cutanea tarda (PCT), the most common form of porphyria, may be one of the rare cutaneous manifestations of hepatic tumors, benign, malignant, or metastatic. The liver damage associated with PCT may predispose to the development of hepatocellular carcinoma. Our experience and a review of the literature suggest that in patients with PCT in whom the usual precipitating factors are absent, or in patients with PCT of long duration and an unexplained exacerbation, liver scan is indicated to rule out the presence of a hepatic tumor."}
{"id": "PMID:207492", "title": "Bactericidal action of ascorbic acid on Psuedomonas aeruginosa: alteration of cell surface as a possible mechanism.", "content": "Neutralised ascorbic acid is found to exert a strong bactericidal action on Pseudomonas aeruginosa suspended in isotonic phosphate buffer at pH 7.1. Both the bactericidal and bacteriostatic action of ascorbic acid are antagonised by magnesium ions. In the absence of complex formation between magnesium and ascorbic acid it is concluded that ascorbic acid acts by competing with the magnesium binding sites in the cell wall, cell membrane or ribosomes. Using the chequer-board titration method the synergistic action of ascorbic acid and erythromycin is determined; such a potentiation of erythromycin is also adversely affected by magnesium ions. P. aeruginosa cells, washed and suspended in isotonic phosphate buffer containing ascorbic acid, became increasingly susceptible to the action of polymyxin, erythromycin, chloramphenicol, neomycin and tetracycline. It is suggested that ascorbic acid alters the cell surface to render it increasingly permeable to these antibiotics.", "contents": "Bactericidal action of ascorbic acid on Psuedomonas aeruginosa: alteration of cell surface as a possible mechanism. Neutralised ascorbic acid is found to exert a strong bactericidal action on Pseudomonas aeruginosa suspended in isotonic phosphate buffer at pH 7.1. Both the bactericidal and bacteriostatic action of ascorbic acid are antagonised by magnesium ions. In the absence of complex formation between magnesium and ascorbic acid it is concluded that ascorbic acid acts by competing with the magnesium binding sites in the cell wall, cell membrane or ribosomes. Using the chequer-board titration method the synergistic action of ascorbic acid and erythromycin is determined; such a potentiation of erythromycin is also adversely affected by magnesium ions. P. aeruginosa cells, washed and suspended in isotonic phosphate buffer containing ascorbic acid, became increasingly susceptible to the action of polymyxin, erythromycin, chloramphenicol, neomycin and tetracycline. It is suggested that ascorbic acid alters the cell surface to render it increasingly permeable to these antibiotics."}
{"id": "PMID:207494", "title": "A hundred years of the hepatotrophic controversy.", "content": "Venous blood returning from the splanchnic viscera has liver-supporting (hepatotrophic) qualities not found to the same degree in other kinds of arterial or venous blood. The effects of portal blood have been noted in animals with two livers (or a differential portal blood supply to different regions of one liver) to include hypertrophy, glycogen storage, hyperplasia, capacity for regeneration, increase of several synthetic functions, and maintenance of normal structure. The main splanchnic venous hepatotrophic factors are endogenous hormones of which the single most important is insulin. Thus, the foregoing portal hepatotrophic effects are largely eliminated with the diabetes produced by alloxan or total pancreatectomy. The injury of portacaval shunt is caused by the diversion of the hormones around the liver. Accordingly, the atrophy, injury to the organelles, and loss of the capacity for cell renewal is minimized if insulin is infused into the portally deprived liver. In these and other experiments, exogenous glucagon alone or the addition of glucagon to insulin has had no effect, but this may be because of the masking presence of gut glucagon and other hormonal or non-hormonal substances in our models. At present, the effects on the liver of exogenous insulin, glucagon, epidermal growth factor, and numerous other hormones are being determined by their intraportal infusion into eviscerated dogs in which other endogenous splanchnic factors have been eliminated.", "contents": "A hundred years of the hepatotrophic controversy. Venous blood returning from the splanchnic viscera has liver-supporting (hepatotrophic) qualities not found to the same degree in other kinds of arterial or venous blood. The effects of portal blood have been noted in animals with two livers (or a differential portal blood supply to different regions of one liver) to include hypertrophy, glycogen storage, hyperplasia, capacity for regeneration, increase of several synthetic functions, and maintenance of normal structure. The main splanchnic venous hepatotrophic factors are endogenous hormones of which the single most important is insulin. Thus, the foregoing portal hepatotrophic effects are largely eliminated with the diabetes produced by alloxan or total pancreatectomy. The injury of portacaval shunt is caused by the diversion of the hormones around the liver. Accordingly, the atrophy, injury to the organelles, and loss of the capacity for cell renewal is minimized if insulin is infused into the portally deprived liver. In these and other experiments, exogenous glucagon alone or the addition of glucagon to insulin has had no effect, but this may be because of the masking presence of gut glucagon and other hormonal or non-hormonal substances in our models. At present, the effects on the liver of exogenous insulin, glucagon, epidermal growth factor, and numerous other hormones are being determined by their intraportal infusion into eviscerated dogs in which other endogenous splanchnic factors have been eliminated."}
{"id": "PMID:207495", "title": "Amino acid transport in isolated hepatocytes: effect of glucagon.", "content": "Amino acid transport was studied in freshly isolated adult rat hepatocytes using non-metabolizable alpha-amino-1-[14C] isobutyric acid and 1-aminocyclopentane-1-[14C] carboxylic acid. In the presence of sodium, hepatocytes concentrated alpha-aminoisobutyric acid; this concentrative component of the transport had properties similar  to transport system A. The sodium-independent transport of aminocyclopentane carboxylic acid had properties similar to transport system L (facilitated diffusion). Glucagon stimulated the influx of alpha-aminoisobutyric acid into hepatocytes. The glucagon effect (a) occurred rapidly, but its full expression required two hours of exposure of the cells to hormone; (b) involved new protein (and possibly RNA) synthesis; and (c) occurred at low concentrations of glucagon (50% effect with 0.4 nm). Glucagon stimulated only system A. Cyclic AMP also stimulated the transport of alpha-aminoisobutyric acid. Freshly isolated hepatocytes appear conveniently suited to the investigation of various aspects of the regulation of liver amino acid transport in normal and pathophysiological states.", "contents": "Amino acid transport in isolated hepatocytes: effect of glucagon. Amino acid transport was studied in freshly isolated adult rat hepatocytes using non-metabolizable alpha-amino-1-[14C] isobutyric acid and 1-aminocyclopentane-1-[14C] carboxylic acid. In the presence of sodium, hepatocytes concentrated alpha-aminoisobutyric acid; this concentrative component of the transport had properties similar  to transport system A. The sodium-independent transport of aminocyclopentane carboxylic acid had properties similar to transport system L (facilitated diffusion). Glucagon stimulated the influx of alpha-aminoisobutyric acid into hepatocytes. The glucagon effect (a) occurred rapidly, but its full expression required two hours of exposure of the cells to hormone; (b) involved new protein (and possibly RNA) synthesis; and (c) occurred at low concentrations of glucagon (50% effect with 0.4 nm). Glucagon stimulated only system A. Cyclic AMP also stimulated the transport of alpha-aminoisobutyric acid. Freshly isolated hepatocytes appear conveniently suited to the investigation of various aspects of the regulation of liver amino acid transport in normal and pathophysiological states."}
{"id": "PMID:207496", "title": "Portacaval shunt for glycogen storage disease and hyperlipidaemia.", "content": "Complete portacaval shunt was used to treat 10 patients with glycogen storage disease. A favourable effect was noted on body growth and a number of metabolic abnormalities. More recently, continous night feedings with an intermittently placed gastric tube or through a gastrostomy has been shown to be helpful either before or after portacaval shunts. Such alimentation techniques may eliminate the need for shunts in some patients and be of adjuvant benefit in others. Portacaval shunt was also used for three children who had homozygous Type II hyperlipidaemia. Substantial reductions in serum cholesterol concentration were observed, as well as resorption of xanthomas. Reversal of some cardiovascular lesions has been documented. The benefits of portacaval shunt in these disorders is probably due to the change in the hormone climate of the liver and the whole organism brought about by diversion of the hormone-rich splanchnic venous blood around the liver.", "contents": "Portacaval shunt for glycogen storage disease and hyperlipidaemia. Complete portacaval shunt was used to treat 10 patients with glycogen storage disease. A favourable effect was noted on body growth and a number of metabolic abnormalities. More recently, continous night feedings with an intermittently placed gastric tube or through a gastrostomy has been shown to be helpful either before or after portacaval shunts. Such alimentation techniques may eliminate the need for shunts in some patients and be of adjuvant benefit in others. Portacaval shunt was also used for three children who had homozygous Type II hyperlipidaemia. Substantial reductions in serum cholesterol concentration were observed, as well as resorption of xanthomas. Reversal of some cardiovascular lesions has been documented. The benefits of portacaval shunt in these disorders is probably due to the change in the hormone climate of the liver and the whole organism brought about by diversion of the hormone-rich splanchnic venous blood around the liver."}
{"id": "PMID:207506", "title": "Entamoeba histolytica and Homo sapiens.", "content": "Blind acceptance of the dicta of the great has led to much confusion as to the relationship between amoeba and man. A review of the mistakes of the past may lead to a better appreciation of the present, and higher hopes for the future. An hypothesis is presented.", "contents": "Entamoeba histolytica and Homo sapiens. Blind acceptance of the dicta of the great has led to much confusion as to the relationship between amoeba and man. A review of the mistakes of the past may lead to a better appreciation of the present, and higher hopes for the future. An hypothesis is presented."}
{"id": "PMID:207509", "title": "Effects of FSH on cyclic nucleotide accumulation in testes of rats of various ages.", "content": "The accumulation of cyclic AMP in rat testis in response to FSH is much greater in immature rat compared to adult. Addition of 3-isobutyl-1-methylxanthine (MIX), a potent in vitro inhibitor of cyclic nucleotide phosphodiesterase activity, potentiates the effects of FSH but does not restore the cyclic AMP response of adult rat to that of immature rat testis. The apparent substrate affinities for cyclic AMP and cyclic GMP hydrolysis are similar in immature and mature testis. Developmental changes in cyclic AMP and cyclic GMP phosphodiesterase specific activities fail to account for the reduced responsiveness of adult testis to FSH. These results suggest a defect in synthetic rather than hydrolytic mechanisms in FSH-responsive cells.", "contents": "Effects of FSH on cyclic nucleotide accumulation in testes of rats of various ages. The accumulation of cyclic AMP in rat testis in response to FSH is much greater in immature rat compared to adult. Addition of 3-isobutyl-1-methylxanthine (MIX), a potent in vitro inhibitor of cyclic nucleotide phosphodiesterase activity, potentiates the effects of FSH but does not restore the cyclic AMP response of adult rat to that of immature rat testis. The apparent substrate affinities for cyclic AMP and cyclic GMP hydrolysis are similar in immature and mature testis. Developmental changes in cyclic AMP and cyclic GMP phosphodiesterase specific activities fail to account for the reduced responsiveness of adult testis to FSH. These results suggest a defect in synthetic rather than hydrolytic mechanisms in FSH-responsive cells."}
{"id": "PMID:207510", "title": "Is cyclic AMP the regulator of hepatic ornithine decarboxylase activity?", "content": "The role of cyclic AMP in the regulation of hepatic ornithine decarboxylase (ODC) activity in the rat was studied in the whole animal and in the perfused organ. Dibutyryl cyclic AMP or butyrate given to intact rats increased ODC activity; this increase was abolished by hypophysectomy 1 h prior to administering ether compound. Administration of 1 mg 1-methyl-3-isobutylxanthine (MIX) to intact rats increased ODC activity within 4 hours whereas hypophysectomy 1 h before treatment prevented this increase. No change in hepatic cyclic AMP content was seen in either intact or hypophysectomized rats following MIX. Perfusion with 0.5 mM dibutyryl cyclic AMP decreased ODC activity in isolated livers whereas perfusion with 0.5 mM 8-bromocyclic GMP produced a small increase in ODC activity. These data suggest that the effect of dibutyryl cyclic AMP in intact animals may be a property of the butyrate and that this action as well as the action of MIX may be mediated through the permissive effect of pituitary and/or adrenal hormones. The normal hepatocyte does not increase its ornithine decarboxylase activity after direct exposure to dibutyryl cyclic AMP.", "contents": "Is cyclic AMP the regulator of hepatic ornithine decarboxylase activity? The role of cyclic AMP in the regulation of hepatic ornithine decarboxylase (ODC) activity in the rat was studied in the whole animal and in the perfused organ. Dibutyryl cyclic AMP or butyrate given to intact rats increased ODC activity; this increase was abolished by hypophysectomy 1 h prior to administering ether compound. Administration of 1 mg 1-methyl-3-isobutylxanthine (MIX) to intact rats increased ODC activity within 4 hours whereas hypophysectomy 1 h before treatment prevented this increase. No change in hepatic cyclic AMP content was seen in either intact or hypophysectomized rats following MIX. Perfusion with 0.5 mM dibutyryl cyclic AMP decreased ODC activity in isolated livers whereas perfusion with 0.5 mM 8-bromocyclic GMP produced a small increase in ODC activity. These data suggest that the effect of dibutyryl cyclic AMP in intact animals may be a property of the butyrate and that this action as well as the action of MIX may be mediated through the permissive effect of pituitary and/or adrenal hormones. The normal hepatocyte does not increase its ornithine decarboxylase activity after direct exposure to dibutyryl cyclic AMP."}
{"id": "PMID:207511", "title": "Effects of thyrotropin and thyroid hormones in vivo on thyroid responsiveness to thyrotropin in vitro.", "content": "The thyroid gland of rats fed propylthiouracil is known to be unresponsive in vitro to thyrotropin; to investigate further the underlying mechanism groups of rats were variously treated with propylthiouracil and thyroid hormone or subjected to hypophysectomy. In vitro responsiveness of the thyroids was tested by measuring an increase in the concentration of c AMP when thyrotropin or prostaglandin E1 was added to the medium. Results showed that responsiveness to thyrotropin partially returned with rats fed prophylthiouracil and hypophysectomized 5, but not 2, days before death; hypophysectomy of normal rats led to increased in vitro responsiveness to thyrotropin and this was partially reversed by injections of thyrotropin for a week before death. Administration of thyroid hormone had little effect in these investigations and in vitro responsiveness to prostaglanding E1 was not consistently influenced by any of the in vivo regimens. From this experience we conclude that, at least as studied in vitro, circulating thyrotropin has a significant role in modulating responsiveness of the thyroid to thyrotropin.", "contents": "Effects of thyrotropin and thyroid hormones in vivo on thyroid responsiveness to thyrotropin in vitro. The thyroid gland of rats fed propylthiouracil is known to be unresponsive in vitro to thyrotropin; to investigate further the underlying mechanism groups of rats were variously treated with propylthiouracil and thyroid hormone or subjected to hypophysectomy. In vitro responsiveness of the thyroids was tested by measuring an increase in the concentration of c AMP when thyrotropin or prostaglandin E1 was added to the medium. Results showed that responsiveness to thyrotropin partially returned with rats fed prophylthiouracil and hypophysectomized 5, but not 2, days before death; hypophysectomy of normal rats led to increased in vitro responsiveness to thyrotropin and this was partially reversed by injections of thyrotropin for a week before death. Administration of thyroid hormone had little effect in these investigations and in vitro responsiveness to prostaglanding E1 was not consistently influenced by any of the in vivo regimens. From this experience we conclude that, at least as studied in vitro, circulating thyrotropin has a significant role in modulating responsiveness of the thyroid to thyrotropin."}
{"id": "PMID:207512", "title": "Role of cyclic nucleotides in modulating ovarian hCG action.", "content": "The role of cyclic nucleotides in mediating hormonally responsive adenylate cyclase and cAMP-dependent protein kinase was examined in vivo and in vitro when pseudopregnant rats were injected with hCG. Intracellular ovarian levels of cAMP increased, as expected, but no change in cGMP concentrations was observed. However, both cGMP and cAMP activated ovarian CDPK holoenzyme in vitro but cGMP had a lower affinity. The subunits of hCG were without effect. Even though cGMP and cAMP dissociate partially purified ovarian CDPK holoenzyme in vitro, the receptor sites of the regulatory subunit of CDPK would appear to be relatively specific for cAMP. Moreover, cGMP probably does not mediate hCG action in vivo.", "contents": "Role of cyclic nucleotides in modulating ovarian hCG action. The role of cyclic nucleotides in mediating hormonally responsive adenylate cyclase and cAMP-dependent protein kinase was examined in vivo and in vitro when pseudopregnant rats were injected with hCG. Intracellular ovarian levels of cAMP increased, as expected, but no change in cGMP concentrations was observed. However, both cGMP and cAMP activated ovarian CDPK holoenzyme in vitro but cGMP had a lower affinity. The subunits of hCG were without effect. Even though cGMP and cAMP dissociate partially purified ovarian CDPK holoenzyme in vitro, the receptor sites of the regulatory subunit of CDPK would appear to be relatively specific for cAMP. Moreover, cGMP probably does not mediate hCG action in vivo."}
{"id": "PMID:207514", "title": "Study of follitropin receptors in testis using a homologous system. Binding of porcine follitropin to plasma membranes from immature porcine testis and correlation with adenylate cyclase stimulation.", "content": "The properties of follitropin receptors in immature porcine testis were determined using highly purified porcine follitropin. 1. The characteristics of follitropin binding to a subcellular fraction rich in plasma membranes were studied using a 125I-labelled follitropin with high specific activity (75-100 Ci/g) and high binding activity. The binding is dependent on time, temperature and pH. It is specific to follitropin as demonstrated by the very low binding activity of the follitropin alpha and beta subunits and of the other glycoprotein hormones. Scatchard analysis of binding data indicated an equilibrium association constant of 2 x 10(10) M-1 and a concentration of high affinity binding sites of 500 fmol/mg membrane proteins. 2. A sensitive radio-ligand receptor assay was developed. Fifty percent inhibition of binding was obtained with as little as 2 ng of porcine follitropin. Ovine and bovine follitropins and pregnant mare serum gonadotropin gave binding inhibition curves parallel to that given by porcine follitropin. With equine and human follitropin, significantly different slopes were recorded. 3. Kinetics of dissociation of labelled follitropin from its testis receptors showed the presence of at least two compartments with fast and slow dissociation rate constants. The ratio between the sizes of the slow and fast compartments appeared dependent upon preincubation time. 4. A temporal correlation was observed between binding of follitropin to testis receptors and activation of membrane bound adenylate cyclase.", "contents": "Study of follitropin receptors in testis using a homologous system. Binding of porcine follitropin to plasma membranes from immature porcine testis and correlation with adenylate cyclase stimulation. The properties of follitropin receptors in immature porcine testis were determined using highly purified porcine follitropin. 1. The characteristics of follitropin binding to a subcellular fraction rich in plasma membranes were studied using a 125I-labelled follitropin with high specific activity (75-100 Ci/g) and high binding activity. The binding is dependent on time, temperature and pH. It is specific to follitropin as demonstrated by the very low binding activity of the follitropin alpha and beta subunits and of the other glycoprotein hormones. Scatchard analysis of binding data indicated an equilibrium association constant of 2 x 10(10) M-1 and a concentration of high affinity binding sites of 500 fmol/mg membrane proteins. 2. A sensitive radio-ligand receptor assay was developed. Fifty percent inhibition of binding was obtained with as little as 2 ng of porcine follitropin. Ovine and bovine follitropins and pregnant mare serum gonadotropin gave binding inhibition curves parallel to that given by porcine follitropin. With equine and human follitropin, significantly different slopes were recorded. 3. Kinetics of dissociation of labelled follitropin from its testis receptors showed the presence of at least two compartments with fast and slow dissociation rate constants. The ratio between the sizes of the slow and fast compartments appeared dependent upon preincubation time. 4. A temporal correlation was observed between binding of follitropin to testis receptors and activation of membrane bound adenylate cyclase."}
{"id": "PMID:207516", "title": "Calcium as modulator of the hormonal-receptors-biological-response coupling system. Effects of Ca2+ ions on the insulin activated 2-deoxyglucose transport in rat fat cells.", "content": "Activation of 2-deoxyglucose transport in isolated rat fat cells by insulin is dependent upon the presence of Ca2+ in the external medium. When calcium concentration is kept below 100 micron, insulin acts like a partial agonist, giving only half of the maximal activation obtained normally with a millimolar concentration of this ion. Oxytocin, whose insulin-like action on adipocytes activates glucose oxidation by these cells, was found to be unable to affect the rate of 2-deoxyglucose transport. This, together with previous observations, suggests that calcium ions play a role in the mechanism of insulin action possibly by binding selectively to membrane sites involved in the transmission of the hormonal message to the glucose carrier. Oxytocin seems to trigger only intracellular glucose metabolism and it appears that there is an absolute requirement for calcium ions in the activation of a still unknown membrane signal.", "contents": "Calcium as modulator of the hormonal-receptors-biological-response coupling system. Effects of Ca2+ ions on the insulin activated 2-deoxyglucose transport in rat fat cells. Activation of 2-deoxyglucose transport in isolated rat fat cells by insulin is dependent upon the presence of Ca2+ in the external medium. When calcium concentration is kept below 100 micron, insulin acts like a partial agonist, giving only half of the maximal activation obtained normally with a millimolar concentration of this ion. Oxytocin, whose insulin-like action on adipocytes activates glucose oxidation by these cells, was found to be unable to affect the rate of 2-deoxyglucose transport. This, together with previous observations, suggests that calcium ions play a role in the mechanism of insulin action possibly by binding selectively to membrane sites involved in the transmission of the hormonal message to the glucose carrier. Oxytocin seems to trigger only intracellular glucose metabolism and it appears that there is an absolute requirement for calcium ions in the activation of a still unknown membrane signal."}
{"id": "PMID:207518", "title": "Cyclic AMP-binding proteins: inverse relationship with estrogen-receptors in hormone-dependent mammary tumor regression.", "content": "Dimethylbenzanthracene-induced rat carcinomas possess activities binding cyclic adenosine 3':5'-monophosphate (cAMP) and estrogen. When dimethylbenzanthracene-induced tumors regress after ovariectomy of the host, a change in the specific binding of cAMP and estrogen occurs in the tumors. Six days after ovariectomy, cAMP binding increases 5-fold in the nuclei and 2-fold in the cytosol of tumors, while nuclear and cytoplasmic estrogen binding decreases by 80% and 50%, respectively. These changes in activities binding cAMP and estrogen are detectable within 1 day after ovariectomy and the changes are reversed when resumption of tumor growth is induced by the injection of 17beta-estradiol. When dimethylbenzanthracene-induced tumors fail to regress after ovariectomy, the change in activities binding cAMP and estrogen does not occur. Significant increases in the cAMP level as well as in adenylate cyclase and cAMP-phosphodiesterase activities are also found in the regressing tumors. Concomitant with the increase of cAMP-binding activity is an increase in histone kinase activity in the regressing tumor. These data suggest the involvement of cAMP in the growth control of a hormone-dependent mammary rumor.", "contents": "Cyclic AMP-binding proteins: inverse relationship with estrogen-receptors in hormone-dependent mammary tumor regression. Dimethylbenzanthracene-induced rat carcinomas possess activities binding cyclic adenosine 3':5'-monophosphate (cAMP) and estrogen. When dimethylbenzanthracene-induced tumors regress after ovariectomy of the host, a change in the specific binding of cAMP and estrogen occurs in the tumors. Six days after ovariectomy, cAMP binding increases 5-fold in the nuclei and 2-fold in the cytosol of tumors, while nuclear and cytoplasmic estrogen binding decreases by 80% and 50%, respectively. These changes in activities binding cAMP and estrogen are detectable within 1 day after ovariectomy and the changes are reversed when resumption of tumor growth is induced by the injection of 17beta-estradiol. When dimethylbenzanthracene-induced tumors fail to regress after ovariectomy, the change in activities binding cAMP and estrogen does not occur. Significant increases in the cAMP level as well as in adenylate cyclase and cAMP-phosphodiesterase activities are also found in the regressing tumors. Concomitant with the increase of cAMP-binding activity is an increase in histone kinase activity in the regressing tumor. These data suggest the involvement of cAMP in the growth control of a hormone-dependent mammary rumor."}
{"id": "PMID:207519", "title": "Effects of steroid hormones on the level of corticotropin messenger RNA activity in cultured mouse-pituitary-tumor cells.", "content": "Studies have been made with the mouse pituitary tumor cell line AtT-20 in culture to determine whether or not the suppression of pituitary corticotropin messenger RNA activity observed upon the administration of glucocorticoids to adrenalectomized rats is due to a direct action of these steroid hormones on the pituitary. The levels of corticotropin messenger RNA activity in AtT-20 cells treated with various steroid hormones were measured with the use of the cell-free protein-synthesizing system derived from wheat germ. The addition of dexamethasone to culture medium reduced the level of corticotropin messenger RNA activity to 30-40% of that in untreated cells. Corticosterone and cortisol exhibited a suppressive effect to a lesser extent. In contrast, nonglucocorticoids such as testosterone and 17beta-estradiol were essentially ineffective. These results indicate that at least part of the glucocorticoid action is exerted directly on the pituitary to suppress corticotropin messenger RNA activity.", "contents": "Effects of steroid hormones on the level of corticotropin messenger RNA activity in cultured mouse-pituitary-tumor cells. Studies have been made with the mouse pituitary tumor cell line AtT-20 in culture to determine whether or not the suppression of pituitary corticotropin messenger RNA activity observed upon the administration of glucocorticoids to adrenalectomized rats is due to a direct action of these steroid hormones on the pituitary. The levels of corticotropin messenger RNA activity in AtT-20 cells treated with various steroid hormones were measured with the use of the cell-free protein-synthesizing system derived from wheat germ. The addition of dexamethasone to culture medium reduced the level of corticotropin messenger RNA activity to 30-40% of that in untreated cells. Corticosterone and cortisol exhibited a suppressive effect to a lesser extent. In contrast, nonglucocorticoids such as testosterone and 17beta-estradiol were essentially ineffective. These results indicate that at least part of the glucocorticoid action is exerted directly on the pituitary to suppress corticotropin messenger RNA activity."}
{"id": "PMID:207520", "title": "Nucleotide sequence of the restriction fragment Hind-F-EcoRI1 of simian-virus-40 DNA (part of the VP1 gene).", "content": "The nucleotide sequence of the simian virus 40 (SV40) genome region between the cleavage sites for restriction endonucleases EcoRI (map position 0) and HindII (map position 0.05) has been determined mainly by the partial chemical DNA degradation procedure of Maxam and Gilbert. This fragment represents 5.3% of the genome of SV40 and is located in the late region, internally in the VP1 gene. The message strand shows only one open reading frame for translation into protein, which connects to the one for the preceding fragment. On this basis part of the amino acid sequence of the VP1 protein is presented.", "contents": "Nucleotide sequence of the restriction fragment Hind-F-EcoRI1 of simian-virus-40 DNA (part of the VP1 gene). The nucleotide sequence of the simian virus 40 (SV40) genome region between the cleavage sites for restriction endonucleases EcoRI (map position 0) and HindII (map position 0.05) has been determined mainly by the partial chemical DNA degradation procedure of Maxam and Gilbert. This fragment represents 5.3% of the genome of SV40 and is located in the late region, internally in the VP1 gene. The message strand shows only one open reading frame for translation into protein, which connects to the one for the preceding fragment. On this basis part of the amino acid sequence of the VP1 protein is presented."}
{"id": "PMID:207521", "title": "Complete nucleotide sequence of the simian-virus 40 Hind-G fragment and localisation of the carboxyl terminus of the VP1 protein.", "content": "The restriction fragment Hind-G represents 7.0% of the simian virus 40 (SV40) genome. The information present in fragment Hind-G is expressed as part of the major, late 16-S messenger RNA. The complete nucleotide sequence of the fragment Hind-G has now been determined by application of the procedure of Maxam and Gilbert [Proc. Natl Acad. Sci. U.S.A. (1977) 74, 560-564]. It contains 369 nucleotide base pairs. On the basis of the termination code words in the strand with the same polarity as the late mRNA, two illegitimate reading frames can be defined. Therefore the third, open frame must code for the carboxyl terminal part of the VP1 protein. It terminates within fragment Hind-G with a TGA signal. This stop codon is followed by a non-translated region of the mRNA of about 83 nucleotides. The latter contains the sequence A-A-U-A-A-A, common to all other eukaryotic mRNA molecules so far studied. The Hind-G fragment also contains sequences which presumably play a role in the synthesis, processing and/or expression of early mRNA; these aspects are discussed in the following paper.", "contents": "Complete nucleotide sequence of the simian-virus 40 Hind-G fragment and localisation of the carboxyl terminus of the VP1 protein. The restriction fragment Hind-G represents 7.0% of the simian virus 40 (SV40) genome. The information present in fragment Hind-G is expressed as part of the major, late 16-S messenger RNA. The complete nucleotide sequence of the fragment Hind-G has now been determined by application of the procedure of Maxam and Gilbert [Proc. Natl Acad. Sci. U.S.A. (1977) 74, 560-564]. It contains 369 nucleotide base pairs. On the basis of the termination code words in the strand with the same polarity as the late mRNA, two illegitimate reading frames can be defined. Therefore the third, open frame must code for the carboxyl terminal part of the VP1 protein. It terminates within fragment Hind-G with a TGA signal. This stop codon is followed by a non-translated region of the mRNA of about 83 nucleotides. The latter contains the sequence A-A-U-A-A-A, common to all other eukaryotic mRNA molecules so far studied. The Hind-G fragment also contains sequences which presumably play a role in the synthesis, processing and/or expression of early mRNA; these aspects are discussed in the following paper."}
{"id": "PMID:207524", "title": "Cytochrome c from Schizosaccharomyces pombe. 1. Purification, spectral properties, and amino-acid composition.", "content": "Cytochrome c from the fission yeast Schizosaccharomyces pombe has been purified. Its chromatographic and spectral properties are reported and compared to those of iso-1-cytochrome c from baker's yeast; the amino-acid composition is described. Schiz. pombe cytochrome c has a much lower affinity for Amberlite IRP64 than Sacch. cerevisiae iso-1-cytochrome c. Its alpha absorption band splits into three maxima (calpha1, calpha2, and calpha3) at -190 degrees C; this is unusual in yeasts, as shown by the low-temperature whole-cell absorption spectra which were examined in various yeast genera, species, and strains. A minor component can be separated by Amberlite chromatography. It exhibits the same low-temperature splitting of the alpha absorption band as the main fraction and it has a similar amino-acid composition with a notable exception: it is an unmethylated form of the cytochrome.", "contents": "Cytochrome c from Schizosaccharomyces pombe. 1. Purification, spectral properties, and amino-acid composition. Cytochrome c from the fission yeast Schizosaccharomyces pombe has been purified. Its chromatographic and spectral properties are reported and compared to those of iso-1-cytochrome c from baker's yeast; the amino-acid composition is described. Schiz. pombe cytochrome c has a much lower affinity for Amberlite IRP64 than Sacch. cerevisiae iso-1-cytochrome c. Its alpha absorption band splits into three maxima (calpha1, calpha2, and calpha3) at -190 degrees C; this is unusual in yeasts, as shown by the low-temperature whole-cell absorption spectra which were examined in various yeast genera, species, and strains. A minor component can be separated by Amberlite chromatography. It exhibits the same low-temperature splitting of the alpha absorption band as the main fraction and it has a similar amino-acid composition with a notable exception: it is an unmethylated form of the cytochrome."}
{"id": "PMID:207525", "title": "Cytochrome c from Schizosaccharomyces pombe. 2. Amino-acid sequence.", "content": "The amino acid sequence of Schizosaccharomyces pombe cytochrome c has been established by automatic degradation of the protein and by manual degradation of fragments obtained by cyanogen bromide cleavage and chymotryptic digestion. The chymotryptic peptides were aligned by homology with other known cytochrome c sequences. The protein is 108 residues long, with a four-residue amino-terminal tail. It has only one methionine residue and differs from other fungal cytochromes c in lacking the one-residue deletion at the C-terminal end. After a cyanogen bromide step, an unexpected cleavage of the peptide chain before a cysteine residue was observed. This is ascribed to formation of a dehydroalanyl residue during an incomplete S-carboxymethylation of the apoprotein, and subsequent cleavage under acidic conditions. Experimental evidence is presented in favour of the proposed mechanisms.", "contents": "Cytochrome c from Schizosaccharomyces pombe. 2. Amino-acid sequence. The amino acid sequence of Schizosaccharomyces pombe cytochrome c has been established by automatic degradation of the protein and by manual degradation of fragments obtained by cyanogen bromide cleavage and chymotryptic digestion. The chymotryptic peptides were aligned by homology with other known cytochrome c sequences. The protein is 108 residues long, with a four-residue amino-terminal tail. It has only one methionine residue and differs from other fungal cytochromes c in lacking the one-residue deletion at the C-terminal end. After a cyanogen bromide step, an unexpected cleavage of the peptide chain before a cysteine residue was observed. This is ascribed to formation of a dehydroalanyl residue during an incomplete S-carboxymethylation of the apoprotein, and subsequent cleavage under acidic conditions. Experimental evidence is presented in favour of the proposed mechanisms."}
{"id": "PMID:207526", "title": "Covalent binding of an NAD analogue to liver alcohol dehydrogenase resulting in an enzyme-coenzyme complex not requiring exogenous coenzyme for activity.", "content": "1. The NAD analogue, N6-[N-(6-aminohexyl)carbamoylmethyl]-NAD, was covalently bound to horse liver alcohol dehydrogenase in a carbodiimide-mediated reaction and in such a way that it was active with the very same enzyme molecule to which it was coupled. 2. The degree of substitution, i.e. the number of NAD analogues per enzyme subunit, could be varied (0.3-1.6). In one preparation 1.6 coenzyme molecules were bound per subunit; the alcohol dehydrogenase activity of this preparation was 40% of the activity obtained after addition of free NAD in excess. 3. It was calculated that every fourth active site of this preparation was provided with a covalently bound functioning coenzyme analogue, and that this analogue had a cycling rate of about 40 000 cycles/h in a coupled substrate assay. 4. The presence of the covalently bound coenzyme made the active sites difficult to inhibit with a competitive inhibitor. For example, 10 mM AMP inhibited the activity of the preparation by 50% whereas a reference system containing native alcohol dehydrogenase was inhibited by 80% in spite of the fact that the reference system contained about 20 000 times as high a concentration of coenzyme.", "contents": "Covalent binding of an NAD analogue to liver alcohol dehydrogenase resulting in an enzyme-coenzyme complex not requiring exogenous coenzyme for activity. 1. The NAD analogue, N6-[N-(6-aminohexyl)carbamoylmethyl]-NAD, was covalently bound to horse liver alcohol dehydrogenase in a carbodiimide-mediated reaction and in such a way that it was active with the very same enzyme molecule to which it was coupled. 2. The degree of substitution, i.e. the number of NAD analogues per enzyme subunit, could be varied (0.3-1.6). In one preparation 1.6 coenzyme molecules were bound per subunit; the alcohol dehydrogenase activity of this preparation was 40% of the activity obtained after addition of free NAD in excess. 3. It was calculated that every fourth active site of this preparation was provided with a covalently bound functioning coenzyme analogue, and that this analogue had a cycling rate of about 40 000 cycles/h in a coupled substrate assay. 4. The presence of the covalently bound coenzyme made the active sites difficult to inhibit with a competitive inhibitor. For example, 10 mM AMP inhibited the activity of the preparation by 50% whereas a reference system containing native alcohol dehydrogenase was inhibited by 80% in spite of the fact that the reference system contained about 20 000 times as high a concentration of coenzyme."}
{"id": "PMID:207527", "title": "Binding of microtubule proteins to DNA: specificity of the interaction.", "content": "Tubulin is detected among the DNA-binding proteins when an extract from fibroblasts is chromatographed on DNA-cellulose. Further purification of the colchicine-binding activity shows that purified tubulin from fibroblasts does not bind to DNA. Depolymerized brain microtubule proteins show a high affinity for DNA. The fraction bound is composed of tubulin and microtubule-associated proteins. Experiments with fractionated microtubule proteins indicate that tubulin-free microtubule associated proteins bind to DNA, while tubulin free of microtubule-associated proteins does not. Microtubule-associated proteins bind better to eukaryotic than to phage DNA suggesting a specificity of the interaction.", "contents": "Binding of microtubule proteins to DNA: specificity of the interaction. Tubulin is detected among the DNA-binding proteins when an extract from fibroblasts is chromatographed on DNA-cellulose. Further purification of the colchicine-binding activity shows that purified tubulin from fibroblasts does not bind to DNA. Depolymerized brain microtubule proteins show a high affinity for DNA. The fraction bound is composed of tubulin and microtubule-associated proteins. Experiments with fractionated microtubule proteins indicate that tubulin-free microtubule associated proteins bind to DNA, while tubulin free of microtubule-associated proteins does not. Microtubule-associated proteins bind better to eukaryotic than to phage DNA suggesting a specificity of the interaction."}
{"id": "PMID:207528", "title": "Localization of the oxytocin receptor in the plasma membrane of rat myometrium.", "content": "The distribution of [3H]oxytocin binding sites among various subcellular fractions of rat myometrium paralleled the distribution of 5'-nucleotidase, a plasma membrane marker enzyme, but not of NADPH-cytochrome c reductase or succinate-cytochrome c reductase, which are endoplasmic reticulum and mitochondrial marker enzymes respectively. [3H]Oxytocin binding to the most enriched plasma membrane fraction showed the degree of selectivity with respect to hormone analogues that is expected for the oxytocin receptor. The binding of oxytocin to this fraction showed an apparent Kd of 1.98 X 10(-9) M and a capacity of 1.28 pmol mg-1. It is concluded that the oxytocin receptor is located on the plasma membrane of the smooth muscle cells of the rat uterus.", "contents": "Localization of the oxytocin receptor in the plasma membrane of rat myometrium. The distribution of [3H]oxytocin binding sites among various subcellular fractions of rat myometrium paralleled the distribution of 5'-nucleotidase, a plasma membrane marker enzyme, but not of NADPH-cytochrome c reductase or succinate-cytochrome c reductase, which are endoplasmic reticulum and mitochondrial marker enzymes respectively. [3H]Oxytocin binding to the most enriched plasma membrane fraction showed the degree of selectivity with respect to hormone analogues that is expected for the oxytocin receptor. The binding of oxytocin to this fraction showed an apparent Kd of 1.98 X 10(-9) M and a capacity of 1.28 pmol mg-1. It is concluded that the oxytocin receptor is located on the plasma membrane of the smooth muscle cells of the rat uterus."}
{"id": "PMID:207530", "title": "Neurological complications in patients with malignant tumors of the nasopharynx.", "content": "Of 150 new cases of nasopharyngeal carcinoma diagnosed in Israel during a 9-year period (nationwide study 1960--1968), 74 patients developed neurological complications. In 92% of the cases, neurologic deficits were confined exclusively to cranial nerves. The majority of these patients presented general symptoms of disease such as neck masses, head and facial pain, or nasal and aural disorders. In 23 patients (34%), the initial presentation was of neurologic disability. The most frequently affected nerves were the abducens and the trigeminal. In the fully developed clinical picture, ocular and trigeminal lesions predominated. 5-year survival in patients with cranial nerve involvement was 21% as compared to 55% in those without such lesions. Survival was not influenced by delayed diagnosis.", "contents": "Neurological complications in patients with malignant tumors of the nasopharynx. Of 150 new cases of nasopharyngeal carcinoma diagnosed in Israel during a 9-year period (nationwide study 1960--1968), 74 patients developed neurological complications. In 92% of the cases, neurologic deficits were confined exclusively to cranial nerves. The majority of these patients presented general symptoms of disease such as neck masses, head and facial pain, or nasal and aural disorders. In 23 patients (34%), the initial presentation was of neurologic disability. The most frequently affected nerves were the abducens and the trigeminal. In the fully developed clinical picture, ocular and trigeminal lesions predominated. 5-year survival in patients with cranial nerve involvement was 21% as compared to 55% in those without such lesions. Survival was not influenced by delayed diagnosis."}
{"id": "PMID:207532", "title": "Role of B cells in the expression of genetic resistance to growth of Rous sarcoma in the chicken.", "content": "Resistance to the development of progressively growing tumors induced by Rous sarcoma virus is a dominant trait controlled by a gene linked to the major histocompatibility complex (MHC). The effect of bursectomy (Bx) on the expression of this trait was studied in two inbred lines of chickens homozygous for different MHC alleles, and which differ with respect to the gene controlling resistance to Rous tumors. The results show that Bx alters the expression of the trait, since genetically resistant birds were rendered highly susceptible to progressive tumor growth. The bursa of Fabricius thus makes an important contribution to resistance. The results do not indicate whether genetic resistance is mediated exclusively by B cells or by another bursa-dependent population.", "contents": "Role of B cells in the expression of genetic resistance to growth of Rous sarcoma in the chicken. Resistance to the development of progressively growing tumors induced by Rous sarcoma virus is a dominant trait controlled by a gene linked to the major histocompatibility complex (MHC). The effect of bursectomy (Bx) on the expression of this trait was studied in two inbred lines of chickens homozygous for different MHC alleles, and which differ with respect to the gene controlling resistance to Rous tumors. The results show that Bx alters the expression of the trait, since genetically resistant birds were rendered highly susceptible to progressive tumor growth. The bursa of Fabricius thus makes an important contribution to resistance. The results do not indicate whether genetic resistance is mediated exclusively by B cells or by another bursa-dependent population."}
{"id": "PMID:207533", "title": "Conditions for maximal synthesis of cyclic AMP by mouse macrophages in response to beta-adrenergic stimulation.", "content": "The synthesis of cyclic AMP by mouse peritoneal macrophages in response to stimulation by isoproterenol was studied as a function of drug concentration, incubation time and cell density. Cyclic AMP levels of macrophages increased 3 to 3.5 times over the control level 20 sec after the addition of 10(-3) M isoproterenol. Under these conditions the dose response could be followed down to an isoproterenol concentration of 10(-6) to 10(-7) M. When cell suspensions were inactivated as early as 1 sec after the addition of the drug, the increase in cyclic AMP was much greater (153 vs. 25 pmol/10(7) cells). Macrophage suspensions of high cell density were less responsive than those of low cell density. In the absence of any inhibitor of phosphodiesterase, the stimulatory effect of isoproterenol was always of short duration. The maximum effect of beta-adrenergic stimulation probably occurs in less than 1 sec at a cell density less than 2 x 10(6) cells/ml. The beta-blocking drug Visken abolished the observed effects.", "contents": "Conditions for maximal synthesis of cyclic AMP by mouse macrophages in response to beta-adrenergic stimulation. The synthesis of cyclic AMP by mouse peritoneal macrophages in response to stimulation by isoproterenol was studied as a function of drug concentration, incubation time and cell density. Cyclic AMP levels of macrophages increased 3 to 3.5 times over the control level 20 sec after the addition of 10(-3) M isoproterenol. Under these conditions the dose response could be followed down to an isoproterenol concentration of 10(-6) to 10(-7) M. When cell suspensions were inactivated as early as 1 sec after the addition of the drug, the increase in cyclic AMP was much greater (153 vs. 25 pmol/10(7) cells). Macrophage suspensions of high cell density were less responsive than those of low cell density. In the absence of any inhibitor of phosphodiesterase, the stimulatory effect of isoproterenol was always of short duration. The maximum effect of beta-adrenergic stimulation probably occurs in less than 1 sec at a cell density less than 2 x 10(6) cells/ml. The beta-blocking drug Visken abolished the observed effects."}
{"id": "PMID:207534", "title": "Shedding of anti-IgM from antibody-coated human lymphoma lines: differences between Epstein-Barr virus-negative lines and their virus-converted sublines.", "content": "In vitro converted, Epstein-Barr (EBV) genome-carrying cell lines showed a reduced ability to shed surface-bound antibodies, compared to their EBV-free parental B lymphoma lines. On the other hand, antibody degradation was higher with EBV-positive cells. Analysis of antibody-coated single cells revealed that cells which failed to redistribute or cap their ligand-bound surface components at 37 degrees C, were also capable of shedding bound antibody. This suggests that capping and shedding are essentially independent phenomena, although both may be influenced by the same virally induced change in the lateral mobility of membrane constituents.", "contents": "Shedding of anti-IgM from antibody-coated human lymphoma lines: differences between Epstein-Barr virus-negative lines and their virus-converted sublines. In vitro converted, Epstein-Barr (EBV) genome-carrying cell lines showed a reduced ability to shed surface-bound antibodies, compared to their EBV-free parental B lymphoma lines. On the other hand, antibody degradation was higher with EBV-positive cells. Analysis of antibody-coated single cells revealed that cells which failed to redistribute or cap their ligand-bound surface components at 37 degrees C, were also capable of shedding bound antibody. This suggests that capping and shedding are essentially independent phenomena, although both may be influenced by the same virally induced change in the lateral mobility of membrane constituents."}
{"id": "PMID:207535", "title": "The protective effect of phentolamine against cardiac arrhythmias in the rat.", "content": "Norepinephrine was given by continuous infusion at a rate of 80 microgram/kg/min for 2 min. Norepinephrine caused the appearance of cardiac arrhythmias, primarily ventricular extrasystoles. The prior administration of phentolamine, even in a dose which did not antagonize the pressor effect of norephinephrine, prevented extrasystole production by norepinephrine. Tolazoline and yohimbine, in doses which did not affect the vasopressor action of norepinephrine, also suppressed extrasystole production. It is concluded that the antiarrhythmic effect of phentolamine, does not require antagonism of alpha-adrenoceptors of the type found in the vasculature, but may involve effects on a different type of alpha-adrenoceptors in the heart.", "contents": "The protective effect of phentolamine against cardiac arrhythmias in the rat. Norepinephrine was given by continuous infusion at a rate of 80 microgram/kg/min for 2 min. Norepinephrine caused the appearance of cardiac arrhythmias, primarily ventricular extrasystoles. The prior administration of phentolamine, even in a dose which did not antagonize the pressor effect of norephinephrine, prevented extrasystole production by norepinephrine. Tolazoline and yohimbine, in doses which did not affect the vasopressor action of norepinephrine, also suppressed extrasystole production. It is concluded that the antiarrhythmic effect of phentolamine, does not require antagonism of alpha-adrenoceptors of the type found in the vasculature, but may involve effects on a different type of alpha-adrenoceptors in the heart."}
{"id": "PMID:207536", "title": "The plasma cyclic AMP response to catecholamines as potentiated by phentolamine in rats.", "content": "Norepinephrine failed to increase plasma cyclic AMP when injected alone into fasted rats, in contrast with sharp increases elicited by isoproterenol, epinephrine or tyramine. In rats pretreated with 6-hydroxydopamine or cocain, however, there was significant increase in plasma cyclic AMP after norepinephrine injection, suggesting that the rapid neuronal catecholamine uptake was at least partly responsible for the lack of norepinephrine action. Phentolamine was very effective in enhancing the epinephrine-, norepinephrine- or tyramine-induced increase in plasma cyclic AMP but without effect on the isoproterenol-induced increase. Blockade of postsynaptic alpha-adrenoceptors, rather than of presynaptic receptors, is likely to be involved in the phentolamine potentiation, since it was even observed in rats treated with 6-hydroxydopamine or cocaine. A discussion is presented regarding the mechanism by which cyclic AMP generation is influenced by the alpha- and beta-adrenoceptor interaction on effector cell membranes.", "contents": "The plasma cyclic AMP response to catecholamines as potentiated by phentolamine in rats. Norepinephrine failed to increase plasma cyclic AMP when injected alone into fasted rats, in contrast with sharp increases elicited by isoproterenol, epinephrine or tyramine. In rats pretreated with 6-hydroxydopamine or cocain, however, there was significant increase in plasma cyclic AMP after norepinephrine injection, suggesting that the rapid neuronal catecholamine uptake was at least partly responsible for the lack of norepinephrine action. Phentolamine was very effective in enhancing the epinephrine-, norepinephrine- or tyramine-induced increase in plasma cyclic AMP but without effect on the isoproterenol-induced increase. Blockade of postsynaptic alpha-adrenoceptors, rather than of presynaptic receptors, is likely to be involved in the phentolamine potentiation, since it was even observed in rats treated with 6-hydroxydopamine or cocaine. A discussion is presented regarding the mechanism by which cyclic AMP generation is influenced by the alpha- and beta-adrenoceptor interaction on effector cell membranes."}
{"id": "PMID:207546", "title": "Properties and connections of cat fastigiospinal neurons.", "content": "1. Neurons in the cat fastigial nucleus that project to the upper cervical spinal segments (fastigiospinal neurons) were fired by antidromic stimulation of the contralateral spinal cord. Dye ejection from the recording electrode was used to show that most neurons were in the rostral half of the fastigial nucleus. 2. Fastigiospinal neurons can be excited and/or inhibited by stimulation of forelimb and hindlimb nerves and by stimulation of the vestibular nerve. These inputs converge on many neurons. 3. Antidromic microstimulation was used to trace fastigiospinal axons to the vicinity of motor nuclei in in C2-C3. 4. The rostral fastigial nucleus was stimulated in preparations with the medial longitudinal fasciculus transected by a wide lesion that impinged on the medial reticular formation in the caudal medulla, to eliminate some potential axon reflexes. Short-latency EPSPs were recorded in some trapezius and biventer-cervicis motoneurons. In many cases there was little or no occlusion between these EPSPs and others evoked by stimulation of the vestibular nerve ipsilateral to the motoneurons. 5. Movement of the stimulating electrode and placement of this electrode lateral to the fastigial nucleus show that the zone from which low threshold EPSPs can be evoked is localized. 6. Latency measurements and lack of temporal facilitation with double shocks suggest that the EPSPs are monosynaptic. The evidence suggests that they are caused by fastigiospinal fibers terminating on motoneurons.", "contents": "Properties and connections of cat fastigiospinal neurons. 1. Neurons in the cat fastigial nucleus that project to the upper cervical spinal segments (fastigiospinal neurons) were fired by antidromic stimulation of the contralateral spinal cord. Dye ejection from the recording electrode was used to show that most neurons were in the rostral half of the fastigial nucleus. 2. Fastigiospinal neurons can be excited and/or inhibited by stimulation of forelimb and hindlimb nerves and by stimulation of the vestibular nerve. These inputs converge on many neurons. 3. Antidromic microstimulation was used to trace fastigiospinal axons to the vicinity of motor nuclei in in C2-C3. 4. The rostral fastigial nucleus was stimulated in preparations with the medial longitudinal fasciculus transected by a wide lesion that impinged on the medial reticular formation in the caudal medulla, to eliminate some potential axon reflexes. Short-latency EPSPs were recorded in some trapezius and biventer-cervicis motoneurons. In many cases there was little or no occlusion between these EPSPs and others evoked by stimulation of the vestibular nerve ipsilateral to the motoneurons. 5. Movement of the stimulating electrode and placement of this electrode lateral to the fastigial nucleus show that the zone from which low threshold EPSPs can be evoked is localized. 6. Latency measurements and lack of temporal facilitation with double shocks suggest that the EPSPs are monosynaptic. The evidence suggests that they are caused by fastigiospinal fibers terminating on motoneurons."}
{"id": "PMID:207547", "title": "Changes in latency and duration of neural responding following developmental auditory deprivation.", "content": "The initial latency of spikes evoked by click stimulation and the duration over which spiking occurred were observed in the inferior colliculi of rats. One ear of these animals had been deprived of early auditory stimulation by ligation of the external meatus. Clicks presented to the normally experienced ears evoked spikes in the opposite colliculus with latencies that depended on the characteristic frequency of the unit. Low-frequency (less than 5 kHz) units had latencies from 6-10 msec. Latencies declined to 3-4 msec for high frequency (greater than 20 kHz) units. After an ear had been deprived of sound from 10 days after birth, response latencies of units in the opposite colliculus with characteristic frequencies below about 10 kHz were comparable to controls, but most units above 10 kHz had latencies 2-3 times control latencies. Spike activity evoked in these units did not continue as long as that for most comparable control units. Ears sound deprived for an equal period from 60 days after birth also had changes in latencies and response durations, but these were much less than in the developmentally deprived. Latencies of gross potentials at the auditory nerve were not affected by early deprivation, indicating a central origin for the latency changes.", "contents": "Changes in latency and duration of neural responding following developmental auditory deprivation. The initial latency of spikes evoked by click stimulation and the duration over which spiking occurred were observed in the inferior colliculi of rats. One ear of these animals had been deprived of early auditory stimulation by ligation of the external meatus. Clicks presented to the normally experienced ears evoked spikes in the opposite colliculus with latencies that depended on the characteristic frequency of the unit. Low-frequency (less than 5 kHz) units had latencies from 6-10 msec. Latencies declined to 3-4 msec for high frequency (greater than 20 kHz) units. After an ear had been deprived of sound from 10 days after birth, response latencies of units in the opposite colliculus with characteristic frequencies below about 10 kHz were comparable to controls, but most units above 10 kHz had latencies 2-3 times control latencies. Spike activity evoked in these units did not continue as long as that for most comparable control units. Ears sound deprived for an equal period from 60 days after birth also had changes in latencies and response durations, but these were much less than in the developmentally deprived. Latencies of gross potentials at the auditory nerve were not affected by early deprivation, indicating a central origin for the latency changes."}
{"id": "PMID:207548", "title": "Retinal afferents form Gray-type-I and type-II synapses in the suprachiasmatic nucleus (rat).", "content": "The synapses of optic nerve afferents in the suprachiasmatic nucleus (SCN) usually form Gray type I (asymmetrical) synapses, but about 13% show clear-cut Gray type II ( symmetrical) active zones. Some presynaptic elements form a Gray type I--active zone with one dendrite and a Gray type II-active zone with another postsynaptic element at the same time. It is discussed whether this variabilility is related to a simultaneous excitatory and inhibitory action, to a variable activity or efficiency of the synapses or to various stages of maturation.", "contents": "Retinal afferents form Gray-type-I and type-II synapses in the suprachiasmatic nucleus (rat). The synapses of optic nerve afferents in the suprachiasmatic nucleus (SCN) usually form Gray type I (asymmetrical) synapses, but about 13% show clear-cut Gray type II ( symmetrical) active zones. Some presynaptic elements form a Gray type I--active zone with one dendrite and a Gray type II-active zone with another postsynaptic element at the same time. It is discussed whether this variabilility is related to a simultaneous excitatory and inhibitory action, to a variable activity or efficiency of the synapses or to various stages of maturation."}
{"id": "PMID:207551", "title": "Evidence for the nonhydrophobic interaction of aromatic, nitrogen-containing compounds with the coenzyme binding site of a NAD-linked D-lactate dehydrogenase.", "content": "Quantitative structure activity relationships suggest that the binding of quinoline and phenanthroline analogs to D-lactate dehydrogenase from the barnacle, Balanus nubilus Darwin, does not involve primarily hydrophobic effects. This phenomenon appears to exist also for other lactate dehydrogenases.", "contents": "Evidence for the nonhydrophobic interaction of aromatic, nitrogen-containing compounds with the coenzyme binding site of a NAD-linked D-lactate dehydrogenase. Quantitative structure activity relationships suggest that the binding of quinoline and phenanthroline analogs to D-lactate dehydrogenase from the barnacle, Balanus nubilus Darwin, does not involve primarily hydrophobic effects. This phenomenon appears to exist also for other lactate dehydrogenases."}
{"id": "PMID:207552", "title": "Chlorpromazine causes vesicle population changes in the monoaminergic synapse of the rat caudate nucleus.", "content": "The population of monoaminergic synaptic vesicles in the rat caudate nucleus remained unchanged or slightly decreased 3 h after chlorpromazine (CP) administration, and clearly increased after 24 h. The diameter of synaptic vesicles became smaller when the vesicles increased. These findings suggest that CP causes presynaptic blocking in part of its actions and leads to a condition in which neural transmission is inactive. In the control animals, population of the vesicles tended to fluctuate following the circadian rhythm.", "contents": "Chlorpromazine causes vesicle population changes in the monoaminergic synapse of the rat caudate nucleus. The population of monoaminergic synaptic vesicles in the rat caudate nucleus remained unchanged or slightly decreased 3 h after chlorpromazine (CP) administration, and clearly increased after 24 h. The diameter of synaptic vesicles became smaller when the vesicles increased. These findings suggest that CP causes presynaptic blocking in part of its actions and leads to a condition in which neural transmission is inactive. In the control animals, population of the vesicles tended to fluctuate following the circadian rhythm."}
{"id": "PMID:207553", "title": "cAMP in spermatozoa taken from different segments of rat epididymis.", "content": "Experimental evidence conclusively indicates that the epididymis is under endocrine control and plays an active role in the process of spermatic maturation.", "contents": "cAMP in spermatozoa taken from different segments of rat epididymis. Experimental evidence conclusively indicates that the epididymis is under endocrine control and plays an active role in the process of spermatic maturation."}
{"id": "PMID:207554", "title": "Adenylate kinase from Rhodospirillum rubrum.", "content": "A partial purification and some properties of adenylate kinase from the photosynthetic bacterium Rhodospirillum rubrum are described.", "contents": "Adenylate kinase from Rhodospirillum rubrum. A partial purification and some properties of adenylate kinase from the photosynthetic bacterium Rhodospirillum rubrum are described."}
{"id": "PMID:207555", "title": "Chemical synthesis of a hexadecapeptide segment of ubiquitin that activates adenylate cyclase and induces lymphocytes to differentiate.", "content": "A hexadecapeptide corresponding to positions 59--74 of ubiquitin was synthesized and purified. The peptide was characterized by its mobility in TLC and electrophoresis, amino acid sequence and composition, and molar rotation. The peptide possessed approximately 40% activity compared with native ubiquitin in each of 3 biological assays in vitro: a) thymocyte induction, b) B cell induction and c) elevation of intracellular cyclic AMP levels in sarcoma 180 cells.", "contents": "Chemical synthesis of a hexadecapeptide segment of ubiquitin that activates adenylate cyclase and induces lymphocytes to differentiate. A hexadecapeptide corresponding to positions 59--74 of ubiquitin was synthesized and purified. The peptide was characterized by its mobility in TLC and electrophoresis, amino acid sequence and composition, and molar rotation. The peptide possessed approximately 40% activity compared with native ubiquitin in each of 3 biological assays in vitro: a) thymocyte induction, b) B cell induction and c) elevation of intracellular cyclic AMP levels in sarcoma 180 cells."}
{"id": "PMID:207556", "title": "Inhibition of liver fructose 1,6-bisphosphatase activity by Zn2+: reversal by imidazole pyruvate.", "content": "Imidazole pyruvate was found to be a very potent natural chelating agent in reversing the inhibition of liver fructose 1,6-bisphosphatase activity by Zn2+. This metabolite may play a physiological role in gluconeogenesis.", "contents": "Inhibition of liver fructose 1,6-bisphosphatase activity by Zn2+: reversal by imidazole pyruvate. Imidazole pyruvate was found to be a very potent natural chelating agent in reversing the inhibition of liver fructose 1,6-bisphosphatase activity by Zn2+. This metabolite may play a physiological role in gluconeogenesis."}
{"id": "PMID:207557", "title": "A promoting action of cyclic GMP on contractions of guinea-pig vas deferens.", "content": "The effect of dbc-GMP has been studied in ductus deferens of the guinea-pig. The nucleotide potentiated the contractions induced by electrical field stimulation and by adrenergic agonists. The site of action was probably in the smooth muscle cell, since the release of excitatory transmittor was not influenced.", "contents": "A promoting action of cyclic GMP on contractions of guinea-pig vas deferens. The effect of dbc-GMP has been studied in ductus deferens of the guinea-pig. The nucleotide potentiated the contractions induced by electrical field stimulation and by adrenergic agonists. The site of action was probably in the smooth muscle cell, since the release of excitatory transmittor was not influenced."}
{"id": "PMID:207558", "title": "Phosphoinositide content in the erythrocyte membrane of rats with spontaneous and renal hypertension.", "content": "The increase of the content of triphosphoinositide in the erythrocyte membrane in rats with spontaneous and renal hypertension and decrease of phosphatidylinositol at spontaneous hypertension were revealed.", "contents": "Phosphoinositide content in the erythrocyte membrane of rats with spontaneous and renal hypertension. The increase of the content of triphosphoinositide in the erythrocyte membrane in rats with spontaneous and renal hypertension and decrease of phosphatidylinositol at spontaneous hypertension were revealed."}
{"id": "PMID:207559", "title": "Criteria for the appearance of post-tetanic potentiation of transmission at central synapses in Helix aspersa.", "content": "Long-lasting potentiation of inhibitory post-synaptic potentials occurs at 2 identifiable synapses in Helix brain. It appears only after tetanic stimulation and after a minimum of 20 impulses. Its amplitude and duration depends on the number of stimuli.", "contents": "Criteria for the appearance of post-tetanic potentiation of transmission at central synapses in Helix aspersa. Long-lasting potentiation of inhibitory post-synaptic potentials occurs at 2 identifiable synapses in Helix brain. It appears only after tetanic stimulation and after a minimum of 20 impulses. Its amplitude and duration depends on the number of stimuli."}
{"id": "PMID:207560", "title": "Behavioural effects of naloxone in rats.", "content": "Naloxone in rats induces a behavioural syndrome closely resembling that induced by intraliquorally injected ACTH peptides. This effect is probably due to a displacement of the ACTH peptides from other receptors (e.g. opiate receptors).", "contents": "Behavioural effects of naloxone in rats. Naloxone in rats induces a behavioural syndrome closely resembling that induced by intraliquorally injected ACTH peptides. This effect is probably due to a displacement of the ACTH peptides from other receptors (e.g. opiate receptors)."}
{"id": "PMID:207561", "title": "Hepatoma induction in the rat by the subcutaneous administration of powdered 3'-methyl-p-dimethylaminoazobenzene.", "content": "A relatively safe and simple procedure was developed for the induction of hepatomas in the rat by the s.c. administration of powdered 3'-methyl-p-dimethylaminoazobenzene.", "contents": "Hepatoma induction in the rat by the subcutaneous administration of powdered 3'-methyl-p-dimethylaminoazobenzene. A relatively safe and simple procedure was developed for the induction of hepatomas in the rat by the s.c. administration of powdered 3'-methyl-p-dimethylaminoazobenzene."}
{"id": "PMID:207562", "title": "Effects of chronic treatment with ACTH on the intracellular levels of cyclic-AMP and cyclic-GMP in the rat adrenal cortex.", "content": "The effects of chronic ACTH treatment on the increase in the intracellular concentration of cyclic-AMP and cyclic-GMP acutely elicited by ACTH in the rat adrenal cortex were investigated. The results are consistent with the hypothesis that chronic ACTH treatment stimulates a) the de novo synthesis of adenylate- and guanylate-cyclase or b) the synthesis of new specific membrane receptors for ACTH.", "contents": "Effects of chronic treatment with ACTH on the intracellular levels of cyclic-AMP and cyclic-GMP in the rat adrenal cortex. The effects of chronic ACTH treatment on the increase in the intracellular concentration of cyclic-AMP and cyclic-GMP acutely elicited by ACTH in the rat adrenal cortex were investigated. The results are consistent with the hypothesis that chronic ACTH treatment stimulates a) the de novo synthesis of adenylate- and guanylate-cyclase or b) the synthesis of new specific membrane receptors for ACTH."}
{"id": "PMID:207563", "title": "[Effect of cyclic adenosine monophosphate and guanosine monophosphate on the aggregation and nucleotide metabolism of the blood platelets].", "content": "Cyclic adenosine- and guanidine-monophosphates (c-AMP and c-GMP) in final concentration of 1.5 mM were found to bring down the aggregation capacity of the rabbit's blood platelets, this being attended by accumulation of AMP. The content of nucleoside triphosphates and nucleoside-diphosphates of the adenyl series in thrombocytes was influenced by the cyclic mononucleotides in different ways, viz. c-AMP increased the level of ATP and forced down that of ADP, while c-GMP, on the contrary, reduced an ATP-concentration and raised the ADP level.", "contents": "[Effect of cyclic adenosine monophosphate and guanosine monophosphate on the aggregation and nucleotide metabolism of the blood platelets]. Cyclic adenosine- and guanidine-monophosphates (c-AMP and c-GMP) in final concentration of 1.5 mM were found to bring down the aggregation capacity of the rabbit's blood platelets, this being attended by accumulation of AMP. The content of nucleoside triphosphates and nucleoside-diphosphates of the adenyl series in thrombocytes was influenced by the cyclic mononucleotides in different ways, viz. c-AMP increased the level of ATP and forced down that of ADP, while c-GMP, on the contrary, reduced an ATP-concentration and raised the ADP level."}
{"id": "PMID:207564", "title": "[Change in the electron paramagnetic resonance signal at g 2.0057 in the tissues of white mice with nitrite hypoxia].", "content": "The EPR signal intensity at g 2.0057 was measured in tissues of albino mice subjected to the action of sodium nitrite. An increased signal in the blood and a decreased one in the liver and spleen were registered, this being accounted for by redistribution of ascorbic acid in the organism due to the action of nitrite.", "contents": "[Change in the electron paramagnetic resonance signal at g 2.0057 in the tissues of white mice with nitrite hypoxia]. The EPR signal intensity at g 2.0057 was measured in tissues of albino mice subjected to the action of sodium nitrite. An increased signal in the blood and a decreased one in the liver and spleen were registered, this being accounted for by redistribution of ascorbic acid in the organism due to the action of nitrite."}
{"id": "PMID:207583", "title": "Threonyl-tRNA synthetase from yeast: aminoacylation of tRNA on its non-accepting 3'-terminal hydroxyl group and its behaviour in enzyme-catalyzed deacylation.", "content": "Methods have been developed by which tRNA Thr may be aminoacylated at the normally non-accepting 3'-terminal ribose OH. Two of the methods utilize the mischarging ability of the synthetases under special conditions of low salt concentration and presence of organic solvents. The third method demonstrates for the first time that for some synthetases the 2',3' specificity may be manipulated by use of similar special conditions. In the case of threonyl-tRNA synthetase, Thr-tRNAThr-C-C-A(3'd) has been synthesised by this method. The behaviour of threonyl esters of tRNAThr-C-C-A, tRNAThr-C-C-A(2'd) and tRNA Thr-C-C-A-(3'd) in the free enzyme-catalyzed deacylation has been studied and the results indicate that the cis diol functional group is necessary for this hydrolysis. The position on the terminal ribose from which the amino acid is removed in this reaction remains to be identified.", "contents": "Threonyl-tRNA synthetase from yeast: aminoacylation of tRNA on its non-accepting 3'-terminal hydroxyl group and its behaviour in enzyme-catalyzed deacylation. Methods have been developed by which tRNA Thr may be aminoacylated at the normally non-accepting 3'-terminal ribose OH. Two of the methods utilize the mischarging ability of the synthetases under special conditions of low salt concentration and presence of organic solvents. The third method demonstrates for the first time that for some synthetases the 2',3' specificity may be manipulated by use of similar special conditions. In the case of threonyl-tRNA synthetase, Thr-tRNAThr-C-C-A(3'd) has been synthesised by this method. The behaviour of threonyl esters of tRNAThr-C-C-A, tRNAThr-C-C-A(2'd) and tRNA Thr-C-C-A-(3'd) in the free enzyme-catalyzed deacylation has been studied and the results indicate that the cis diol functional group is necessary for this hydrolysis. The position on the terminal ribose from which the amino acid is removed in this reaction remains to be identified."}
{"id": "PMID:207584", "title": "Prognosis in primary amenorrhea.", "content": "A retrospective review of 62 patients with primary amenorrhea indicates that thoughtful clinical evaluation combined with dynamic hypothalamic-pituitary testing can usually determine the etiology and prognosis. A careful history, consideration of chronologic age/bone age/height relationships, and assay of serum gonadotropins distinguished all patients with medical diseases, ovarian failure, hypogonadotropic hypogonadism, and polycystic ovaries. Luteinizing hormone-releasing hormone (LH-RH) stimulation, sometimes combined with clomiphene therapy and estrogen provocation tests, assisted with prognostic and pathophysiologic evaluation, although patient management rarely changed. An age-inappropriate LH-RH test result was helpful in identifying patients with abnormal maturational patterns.", "contents": "Prognosis in primary amenorrhea. A retrospective review of 62 patients with primary amenorrhea indicates that thoughtful clinical evaluation combined with dynamic hypothalamic-pituitary testing can usually determine the etiology and prognosis. A careful history, consideration of chronologic age/bone age/height relationships, and assay of serum gonadotropins distinguished all patients with medical diseases, ovarian failure, hypogonadotropic hypogonadism, and polycystic ovaries. Luteinizing hormone-releasing hormone (LH-RH) stimulation, sometimes combined with clomiphene therapy and estrogen provocation tests, assisted with prognostic and pathophysiologic evaluation, although patient management rarely changed. An age-inappropriate LH-RH test result was helpful in identifying patients with abnormal maturational patterns."}
{"id": "PMID:207603", "title": "Hormonal control of mRNA synthesis studied by nucleic acid hybridization.", "content": "The regulation of protein synthesis by steroids is thought to be due to hormonal effects primarily on mRNA concentration. Experimental evidence to support this conclusion has come largely from the use of DNA probes complementary (cDNA) to mRNA molecules or by translation of the mRNA in vitro. In this review the experimental procedures involved and the application to hormone action of cDNA hybridization will be reviewed. (1) mRNA concentrations can be assayed in tissue RNA samples by hybridization with radiolabelled complementary DNA probes (cDNA). From the rate of hybridization of an mRNA preparation to a cDNA probe it is possible to estimate specific mRNA concentrations and thereby study their hormonal regulation within tissues of subcellular fractions (2) Rates of synthesis of a specific RNA can be measured by hybridization of pulse-labelled RNA with excess cold cDNA as illustrated in studies of the glucocorticoid induction of MMTV RNA. (3) Hormore-induced alterations of mRNA populations as a whole can be investigated. From the kinetics of hybridization of mRNA with its complementary DNA it is possible to estimate the number of different RNA sequences in tissues and to approximate the number of copies of each sequence per cell. Consequently, by comparing mRNA samples isolated from tissues of different hormonal status it is possible to demonstrate specific hormone-inducible mRNA species and, in some cases, identify their translation products.", "contents": "Hormonal control of mRNA synthesis studied by nucleic acid hybridization. The regulation of protein synthesis by steroids is thought to be due to hormonal effects primarily on mRNA concentration. Experimental evidence to support this conclusion has come largely from the use of DNA probes complementary (cDNA) to mRNA molecules or by translation of the mRNA in vitro. In this review the experimental procedures involved and the application to hormone action of cDNA hybridization will be reviewed. (1) mRNA concentrations can be assayed in tissue RNA samples by hybridization with radiolabelled complementary DNA probes (cDNA). From the rate of hybridization of an mRNA preparation to a cDNA probe it is possible to estimate specific mRNA concentrations and thereby study their hormonal regulation within tissues of subcellular fractions (2) Rates of synthesis of a specific RNA can be measured by hybridization of pulse-labelled RNA with excess cold cDNA as illustrated in studies of the glucocorticoid induction of MMTV RNA. (3) Hormore-induced alterations of mRNA populations as a whole can be investigated. From the kinetics of hybridization of mRNA with its complementary DNA it is possible to estimate the number of different RNA sequences in tissues and to approximate the number of copies of each sequence per cell. Consequently, by comparing mRNA samples isolated from tissues of different hormonal status it is possible to demonstrate specific hormone-inducible mRNA species and, in some cases, identify their translation products."}
{"id": "PMID:207604", "title": "The effect of epinephrine and dibutyryl cyclic AMP on glucose 1,6-bisphosphate levels and the activities of hexokinase, phosphofructokinase and phosphoglucomutase in the isolated rat diaphragm.", "content": "Based on previous studies which have revealed that glucose 1,6-bisphosphate (Glc-1,6-P2) is a potent inhibitor of muscle hexokinase and an activator (deinhibitor) of phosphofructokinase and phosphoglucomutase, the effect of epinephrine on the levels of this regulator in rat diaphragm muscle was investigated. It was found that epinephrine caused an increase in diaphragm Glc-1,6-P2 levels, accompanied by a reduction in the activity of hexokinase and an activation (deinhibition) of phosphofructokinase and phosphoglucomutase. N6-2'-O-dibutyryl cyclic AMP was able to mimic all these effects of epinephrine. The concentration of glucose-6-phosphate was not changed by epinephrine, under conditions in which the hormone produced an increase in cyclic AMP and Glc-1,6-P2 levels and the concomitant decrease in hexokinase activity. It was also shown that Glc-1,6-P, in the concentration range found after epinephrine, inhibited the diaphragm hexokinase and deinhibited phosphoglucomutase. These results may suggest a mechanism of epinephrine action by which the activities of hexokinase, phosphoglucomutase and phosphofructokinase, through the action of Glc-1,6-P2, are synchronized with the cyclic AMP-mediated activation of glycogen phosphorylase, to achieve an increase in total glycogenolysis and glycolysis and a concomitant reduction in glucose utilization by the muscle.", "contents": "The effect of epinephrine and dibutyryl cyclic AMP on glucose 1,6-bisphosphate levels and the activities of hexokinase, phosphofructokinase and phosphoglucomutase in the isolated rat diaphragm. Based on previous studies which have revealed that glucose 1,6-bisphosphate (Glc-1,6-P2) is a potent inhibitor of muscle hexokinase and an activator (deinhibitor) of phosphofructokinase and phosphoglucomutase, the effect of epinephrine on the levels of this regulator in rat diaphragm muscle was investigated. It was found that epinephrine caused an increase in diaphragm Glc-1,6-P2 levels, accompanied by a reduction in the activity of hexokinase and an activation (deinhibition) of phosphofructokinase and phosphoglucomutase. N6-2'-O-dibutyryl cyclic AMP was able to mimic all these effects of epinephrine. The concentration of glucose-6-phosphate was not changed by epinephrine, under conditions in which the hormone produced an increase in cyclic AMP and Glc-1,6-P2 levels and the concomitant decrease in hexokinase activity. It was also shown that Glc-1,6-P, in the concentration range found after epinephrine, inhibited the diaphragm hexokinase and deinhibited phosphoglucomutase. These results may suggest a mechanism of epinephrine action by which the activities of hexokinase, phosphoglucomutase and phosphofructokinase, through the action of Glc-1,6-P2, are synchronized with the cyclic AMP-mediated activation of glycogen phosphorylase, to achieve an increase in total glycogenolysis and glycolysis and a concomitant reduction in glucose utilization by the muscle."}
{"id": "PMID:207605", "title": "Dissociation of specific binding of 25-OH-D3 and resorption in fetal rat bones.", "content": "Specific binding of 25-OH-D 3 was measured in cytosol prepared from isolated fetal rat bone cells. Binding was significant after 2 h incubation at 0 degrees C and appeared to be approaching a plateau at 4 h. Binding was half-maximal at 1.7 X 10(-10) M 25-OH-D3. 24(R),25-(OH)2D3, which was approximately equipotent with 25-OH-D3 in bone culture, had approximately the same binding activity. 1,25-(OH)2D3, which was 2--3 orders of magnitude more active on resorption, was a much weaker competitor for binding. Vitamin D3, which was inactive in culture, was at least as effective a competitor as 1,25-(OH)2D3. The results suggest that the cytosol site which specifically bind 25-OH-D3 is not the mediator of the bone-resorbing activity.", "contents": "Dissociation of specific binding of 25-OH-D3 and resorption in fetal rat bones. Specific binding of 25-OH-D 3 was measured in cytosol prepared from isolated fetal rat bone cells. Binding was significant after 2 h incubation at 0 degrees C and appeared to be approaching a plateau at 4 h. Binding was half-maximal at 1.7 X 10(-10) M 25-OH-D3. 24(R),25-(OH)2D3, which was approximately equipotent with 25-OH-D3 in bone culture, had approximately the same binding activity. 1,25-(OH)2D3, which was 2--3 orders of magnitude more active on resorption, was a much weaker competitor for binding. Vitamin D3, which was inactive in culture, was at least as effective a competitor as 1,25-(OH)2D3. The results suggest that the cytosol site which specifically bind 25-OH-D3 is not the mediator of the bone-resorbing activity."}
{"id": "PMID:207606", "title": "Regulation of cholesterol metabolism in rat adrenal mitochondria.", "content": "Addition of cholesterol to rat adrenal mitochondria resulted in a stimulation of pregnenolone synthesis. The slow step of the mitochondrial cholesterol side-chain cleavage reaction could be the interaction of the sterol with cytochrome P-450. The rate of cholesterol binding to this enzyme as observed spectroscopically correlated with the equilibration period (20 min) of the mitochondria and exogenous cholesterol required for maximal rates of pregnenolone synthesis. It is suggested that translocation of cholesterol between different sterol pools occurs within the mitochondria. Potential intracellular effectors that could be of importance in the movement or regulation of mitochondrial cholesterol include bivalent metallic ions, prostaglandins, cyclic nucleotides, polyamines and polylysine. Of the effectors studied, only calcium ions and polylysine markedly stimulated pregnenolone synthesis. These effectors might stimulate steroidogenesis by lateral displacement of cholesterol in the mitochondrial membrane into a compartment easily accessible to the cholesterol side-chain cleavage enzyme complex.", "contents": "Regulation of cholesterol metabolism in rat adrenal mitochondria. Addition of cholesterol to rat adrenal mitochondria resulted in a stimulation of pregnenolone synthesis. The slow step of the mitochondrial cholesterol side-chain cleavage reaction could be the interaction of the sterol with cytochrome P-450. The rate of cholesterol binding to this enzyme as observed spectroscopically correlated with the equilibration period (20 min) of the mitochondria and exogenous cholesterol required for maximal rates of pregnenolone synthesis. It is suggested that translocation of cholesterol between different sterol pools occurs within the mitochondria. Potential intracellular effectors that could be of importance in the movement or regulation of mitochondrial cholesterol include bivalent metallic ions, prostaglandins, cyclic nucleotides, polyamines and polylysine. Of the effectors studied, only calcium ions and polylysine markedly stimulated pregnenolone synthesis. These effectors might stimulate steroidogenesis by lateral displacement of cholesterol in the mitochondrial membrane into a compartment easily accessible to the cholesterol side-chain cleavage enzyme complex."}
{"id": "PMID:207612", "title": "Synthesis and secretion of transferrin by cultured mouse hepatoma cells.", "content": "The mouse hepatoma cell (Hepa-1) in tissue culture has been shown to synthesize and secrete three electrophoretically distinct transferrins. Each of these forms of transferrin has a molecular weight of 77,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The concentration of each form is indicated by its staining intensity, which is highest in the form with the fastest mobility and lowest in the form with the slowest mobility. The relative rate of transferrin synthesis has been determined in log-phase and stationary-phase cells; the data indicate that the relative rate of synthesis increases twofold in stationary-phase cells. When the incorporation of [3H]leucine into transferrin reaches steady state, the rate of secretion is equal to the rate of synthesis; the rate of secretion also increases twofold in stationary-phase cells. Our studies also show that transferrin synthesis accounts for 0.98% of the total protein synthesis in log-phase cells and for 1.8% in stationary-phase cells. This is the level of synthesis that has been determined by in vivo studies. We conclude that after continuous culture for several years these hepatoma cells have maintained one of the characteristics of the differentiated liver cell, namely, the ability to synthesize and secrete transferrin.", "contents": "Synthesis and secretion of transferrin by cultured mouse hepatoma cells. The mouse hepatoma cell (Hepa-1) in tissue culture has been shown to synthesize and secrete three electrophoretically distinct transferrins. Each of these forms of transferrin has a molecular weight of 77,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The concentration of each form is indicated by its staining intensity, which is highest in the form with the fastest mobility and lowest in the form with the slowest mobility. The relative rate of transferrin synthesis has been determined in log-phase and stationary-phase cells; the data indicate that the relative rate of synthesis increases twofold in stationary-phase cells. When the incorporation of [3H]leucine into transferrin reaches steady state, the rate of secretion is equal to the rate of synthesis; the rate of secretion also increases twofold in stationary-phase cells. Our studies also show that transferrin synthesis accounts for 0.98% of the total protein synthesis in log-phase cells and for 1.8% in stationary-phase cells. This is the level of synthesis that has been determined by in vivo studies. We conclude that after continuous culture for several years these hepatoma cells have maintained one of the characteristics of the differentiated liver cell, namely, the ability to synthesize and secrete transferrin."}
{"id": "PMID:207613", "title": "Changes in the cyclic AMP content during growth and development of Acetabularia.", "content": "The 3',5'-adenosine monophosphate (cyclic-AMP) content of the unicellular alga Acetabularia has been examined at various developmental stages. It has been found that very young algae, less than 10mm in length, have a high cAMP content [more than 7 pmoles per 100 mg wet weight (WW)], but that with the growth of the algae, the cAMP content decreases rapidly, reaching the low level of 0.5--1.0 pmoles per 100mg WW. The cAMP content remains at this level until cap differentiation, after which an increase in cAMP content accompanies cap enlargement. It has been shown that these results are unlikely to be affected by changes in the cAMP content induced by variations in circadian rhythm. Treatment with theophylline (2.10(-3) M), a phosphodieterase inhibitor, results in an increase in the cAMP content and delays growth and cap formation. Experiments on the effects of theophylline upon the circadian rhythm of oxygen evolution have shown that the continuous presence of theophylline in the culture medium does not induce a phase shift in the rhythm. The cAMP content of anucleate Acetabularia shows development stage variations parallel to that of the whole algae.", "contents": "Changes in the cyclic AMP content during growth and development of Acetabularia. The 3',5'-adenosine monophosphate (cyclic-AMP) content of the unicellular alga Acetabularia has been examined at various developmental stages. It has been found that very young algae, less than 10mm in length, have a high cAMP content [more than 7 pmoles per 100 mg wet weight (WW)], but that with the growth of the algae, the cAMP content decreases rapidly, reaching the low level of 0.5--1.0 pmoles per 100mg WW. The cAMP content remains at this level until cap differentiation, after which an increase in cAMP content accompanies cap enlargement. It has been shown that these results are unlikely to be affected by changes in the cAMP content induced by variations in circadian rhythm. Treatment with theophylline (2.10(-3) M), a phosphodieterase inhibitor, results in an increase in the cAMP content and delays growth and cap formation. Experiments on the effects of theophylline upon the circadian rhythm of oxygen evolution have shown that the continuous presence of theophylline in the culture medium does not induce a phase shift in the rhythm. The cAMP content of anucleate Acetabularia shows development stage variations parallel to that of the whole algae."}
{"id": "PMID:207615", "title": "Concanavalin-mediated attachment to membranes of a cellular slime mould cyclic AMP phosphodiesterase.", "content": "In the cellular slime mould Dictyostelium, a membrane-bound cyclic AMP phosphodiesterase undergoes a tenfold increase in activity when amoebae reach the aggregation stage of development. Our previous studies had shown that when non-aggregating cells, which produce extracellular and intracellular forms of the enzyme, are treated with the lectin Concanavalin A (Con A), they exhibit prematurely high levels of the membrane bound enzyme. The present results indicate that this effect may be largely due not to the induction of the enzyme by Con A but rather to the binding of the intracellular form of the enzyme to membranes by Con A. This conclusion is based on the findings that: a) the enzyme activity associated with membranes from Con A treated cells can be decreased by treatment with the haptenic sugar alpha-methyl mannoside: b) mambranes from untreated cells having only low membrane-bound phosphodiesterase activity can acquire increased activity after incubation with Con A and intracellular phosphodiesterase; c) the intracellular phosphodiesterase binds to Sepharose-Con A and is eluted with alpha-methyl mannoside. These results raise the possibility that some of the effects attributed to Con A in the literature may not be due directly to Con A but to glycoproteins attached to membranes by Con A.", "contents": "Concanavalin-mediated attachment to membranes of a cellular slime mould cyclic AMP phosphodiesterase. In the cellular slime mould Dictyostelium, a membrane-bound cyclic AMP phosphodiesterase undergoes a tenfold increase in activity when amoebae reach the aggregation stage of development. Our previous studies had shown that when non-aggregating cells, which produce extracellular and intracellular forms of the enzyme, are treated with the lectin Concanavalin A (Con A), they exhibit prematurely high levels of the membrane bound enzyme. The present results indicate that this effect may be largely due not to the induction of the enzyme by Con A but rather to the binding of the intracellular form of the enzyme to membranes by Con A. This conclusion is based on the findings that: a) the enzyme activity associated with membranes from Con A treated cells can be decreased by treatment with the haptenic sugar alpha-methyl mannoside: b) mambranes from untreated cells having only low membrane-bound phosphodiesterase activity can acquire increased activity after incubation with Con A and intracellular phosphodiesterase; c) the intracellular phosphodiesterase binds to Sepharose-Con A and is eluted with alpha-methyl mannoside. These results raise the possibility that some of the effects attributed to Con A in the literature may not be due directly to Con A but to glycoproteins attached to membranes by Con A."}
{"id": "PMID:207616", "title": "Method for the preparation of active maturation promoting factor (MPF) from in vitro matured oocytes of Xenopus laevis.", "content": "A method for the large scale extraction of Maturation Promoting Factor (MPF) from in vitro matured oocytes of Xenopus laevis is described. MPF has been previously described only as a component(s) of hormone-matured cytoplasm within amphibian oocytes (or eggs) which is able to induce the reinitiation of the meiotic process from late diplotene stage until second metaphase arrest, when microinjected into diplotene arrested (fully grown) recipient oocytes. Standard biochemical methods for the extraction and purification of this factor(s) haven been unsuccessful due to its extreme instability and sensitivity to dilution. The procedure is dependent upon the inclusion of sodium fluoride (NaF) in the extraction medium with its effect presumably due to its ability to inhibit phosphorprotein phosphatases. The successful preservation of MPF activity described in this report permits further attempts to be made to isolate and characterize this, to date, elusive cytoplasmic factor, which plays a key role in the complex cellular processes involved in the hormone-dependent differentiation of an oocyte into an egg.", "contents": "Method for the preparation of active maturation promoting factor (MPF) from in vitro matured oocytes of Xenopus laevis. A method for the large scale extraction of Maturation Promoting Factor (MPF) from in vitro matured oocytes of Xenopus laevis is described. MPF has been previously described only as a component(s) of hormone-matured cytoplasm within amphibian oocytes (or eggs) which is able to induce the reinitiation of the meiotic process from late diplotene stage until second metaphase arrest, when microinjected into diplotene arrested (fully grown) recipient oocytes. Standard biochemical methods for the extraction and purification of this factor(s) haven been unsuccessful due to its extreme instability and sensitivity to dilution. The procedure is dependent upon the inclusion of sodium fluoride (NaF) in the extraction medium with its effect presumably due to its ability to inhibit phosphorprotein phosphatases. The successful preservation of MPF activity described in this report permits further attempts to be made to isolate and characterize this, to date, elusive cytoplasmic factor, which plays a key role in the complex cellular processes involved in the hormone-dependent differentiation of an oocyte into an egg."}
{"id": "PMID:207621", "title": "Differential enzyme distribution in lobules of livers from young and old mice and rats.", "content": "In the livers from young (3-6 month) and old (30 month) C57/BL mice and BN/Bi rats light microscope histochemistry has shown that enzyme activity is not always distributed evenly throughout the lobule. The mitochondrial enzyme succinic dehydrogenase, the plasma membrane enzyme 5'-nucleotidase and the endoplasmic reticulum enzyme glucose-6-phosphatase showed heavier reaction product in the perioportal regions of the lobule compared with the centrilobular regions. Alkaline phosphatase showed an altered distribution pattern with age: in young livers this was uniform throughout the lobule while in old livers there was enhanced peripoertal activity. Electron microscope cytochemistry showed that this was due to increased numbers of bile canaliculi in this region containing reaction product and to the additional presence of reaction product associated with the microvilli lining the space of Disse.", "contents": "Differential enzyme distribution in lobules of livers from young and old mice and rats. In the livers from young (3-6 month) and old (30 month) C57/BL mice and BN/Bi rats light microscope histochemistry has shown that enzyme activity is not always distributed evenly throughout the lobule. The mitochondrial enzyme succinic dehydrogenase, the plasma membrane enzyme 5'-nucleotidase and the endoplasmic reticulum enzyme glucose-6-phosphatase showed heavier reaction product in the perioportal regions of the lobule compared with the centrilobular regions. Alkaline phosphatase showed an altered distribution pattern with age: in young livers this was uniform throughout the lobule while in old livers there was enhanced peripoertal activity. Electron microscope cytochemistry showed that this was due to increased numbers of bile canaliculi in this region containing reaction product and to the additional presence of reaction product associated with the microvilli lining the space of Disse."}
{"id": "PMID:207617", "title": "[Biochemical, enzymatic and cultural characteristics and criteria of pathogenicity of staphylocci (study of strains isolated in a hospital environment)].", "content": "The Authors have examined the coagulase activity, mannitol fermentation, DNase and phosphatase activity, and production of haemolisins and pigment on 200 strains of Staphylococcus isolated from hospitalized patients affected by various diseases. On the basis of results obtained, they conclude that the evaluation of the pathogenic power of Stah. aureus should be always founded upon a \"pattern\" of biochemical, enzymatic, cultural and toxinogenetic tests.", "contents": "[Biochemical, enzymatic and cultural characteristics and criteria of pathogenicity of staphylocci (study of strains isolated in a hospital environment)]. The Authors have examined the coagulase activity, mannitol fermentation, DNase and phosphatase activity, and production of haemolisins and pigment on 200 strains of Staphylococcus isolated from hospitalized patients affected by various diseases. On the basis of results obtained, they conclude that the evaluation of the pathogenic power of Stah. aureus should be always founded upon a \"pattern\" of biochemical, enzymatic, cultural and toxinogenetic tests."}
{"id": "PMID:207626", "title": "Activity of some mitochondrial enzymes in the progeny of rabbits treated with dichlorvos in the gestation period.", "content": "The activities of cytochrome oxidase (CYO) and succinate dehydrogenase (SDH) in brains of progeny of rabbits treated with dichlorvos (DDVP) 6 mg/kg/day during last ten days of pregnancy were investigated. Biochemical estimation of mitochondrial fraction of the brain tissue and the histochemical studies of fresh cryostat slices were carried out in 1, 8 and 16 day old rabbits. In comparison with control animals the decrease in CYO and SDH activity and the disturbances in \"enzymatic maturation\" rythm were observed in progeny of rabbits submitted to treatment with DDVP. In neuropil the changes were more pronounced than in pericarium of the nerve cells. In the brain structures which are sensitive to the metabolic disturbances (Ammon horn) SDH activities decreased.", "contents": "Activity of some mitochondrial enzymes in the progeny of rabbits treated with dichlorvos in the gestation period. The activities of cytochrome oxidase (CYO) and succinate dehydrogenase (SDH) in brains of progeny of rabbits treated with dichlorvos (DDVP) 6 mg/kg/day during last ten days of pregnancy were investigated. Biochemical estimation of mitochondrial fraction of the brain tissue and the histochemical studies of fresh cryostat slices were carried out in 1, 8 and 16 day old rabbits. In comparison with control animals the decrease in CYO and SDH activity and the disturbances in \"enzymatic maturation\" rythm were observed in progeny of rabbits submitted to treatment with DDVP. In neuropil the changes were more pronounced than in pericarium of the nerve cells. In the brain structures which are sensitive to the metabolic disturbances (Ammon horn) SDH activities decreased."}
{"id": "PMID:207627", "title": "[Possible roles of prostaglandins in the hypothalamus (author's transl)].", "content": "The last decade has been the most prolific and stimulating period in the area of prostaglandin (PG) study. Since PGs were found in the hypothalamus and cerebrospinal fluid, and were released from the central nervous system (CNS) spontaneously and in response to chemical or electric stimulation, many investigators have been engaged in studying their effects in the CNS. In fact, PGs have a wide range of pharmacological actions in the CNS. Relatively large doses of PGs have to be given centrally to produce some effects. On the other hand, some types of PGs, when applied centrally in doses of a few ng, stimulate the hypothalamus or the pituitary gland to increase secretion of hypothalamic and anterior and also posterior pituitary hormones. Physiological investigations of PGs have been aided by the use of inhibitors of their synthesis; aspirin, indomethacin etc. These compounds inhibit secretion of the hormones from the hypothalamus as well as the pituitary, suggesting that endogenous PGs exert a functional role for the hormone secretion. To produce fever, PGEs have to act on the preoptic anterior hypothalamus, and aspirin and indomethacin decrease fever produced by pyrogens but not PGEs. Pyrogens produce fever by increasing synthesis and release of PGEs. Hypothalamic PGEs play a role as a central transmitter or modulator in temperature regulation.", "contents": "[Possible roles of prostaglandins in the hypothalamus (author's transl)]. The last decade has been the most prolific and stimulating period in the area of prostaglandin (PG) study. Since PGs were found in the hypothalamus and cerebrospinal fluid, and were released from the central nervous system (CNS) spontaneously and in response to chemical or electric stimulation, many investigators have been engaged in studying their effects in the CNS. In fact, PGs have a wide range of pharmacological actions in the CNS. Relatively large doses of PGs have to be given centrally to produce some effects. On the other hand, some types of PGs, when applied centrally in doses of a few ng, stimulate the hypothalamus or the pituitary gland to increase secretion of hypothalamic and anterior and also posterior pituitary hormones. Physiological investigations of PGs have been aided by the use of inhibitors of their synthesis; aspirin, indomethacin etc. These compounds inhibit secretion of the hormones from the hypothalamus as well as the pituitary, suggesting that endogenous PGs exert a functional role for the hormone secretion. To produce fever, PGEs have to act on the preoptic anterior hypothalamus, and aspirin and indomethacin decrease fever produced by pyrogens but not PGEs. Pyrogens produce fever by increasing synthesis and release of PGEs. Hypothalamic PGEs play a role as a central transmitter or modulator in temperature regulation."}
{"id": "PMID:207628", "title": "[Influence of clonazepam, an anticonvulsant benzodiazepine drug, on the rat brain monoamine containing neurons especially on dopaminergic neurons (author's transl)].", "content": "Clonazepam at two doses of 1 mg/kg i.p. significantly decreased 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) contents in the rat caudatus and cortex but not so in the olfactory tubercle, septum and hypothalamus. The drug decreased dopamine (DA) turnover rate in the caudatus, but did not inhibit tyrosine hydroxylase activity. The drug significantly enhanced stereotyped behavior induced by apomorphine and d-methamphetamine. Clonazepam enhanced apomorphine-induced decrease in striatal HVA, and cortical DOPAC and HVA contents, and d-methamphetamine-induced decrease in cortical DOPAC content. Reserpine pretreatment did not affect apomorphine-induced stereotypy and its enhancement with clonazepam. The drug did not activate adenylate cyclase nor DA-sensitive adenylate cyclase in the striatal homogenates and did not change cyclic AMP content in the caudatus. The drug inhibited phosphodiesterase activity in caudate and cortical homogenates but not in vivo. Clonazepam did not alter ChAc and AChE activities in the caudatus, 6 other cerebral regions and the spinal area. Clonazepam also decreased NE turnover in the caudatus and 5-HIAA contents in the brainstem area. These neurochemical and behavioral effects of clonazepam indicate probable postjunctional DA stimulation in the striatum and cortex of the type not linked with adenylate cyclase and phosphodiesterase but probably due to activation of inhibitory gamma-amino butyric acid (GABA) neurons on the strio-nigral pathway.", "contents": "[Influence of clonazepam, an anticonvulsant benzodiazepine drug, on the rat brain monoamine containing neurons especially on dopaminergic neurons (author's transl)]. Clonazepam at two doses of 1 mg/kg i.p. significantly decreased 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) contents in the rat caudatus and cortex but not so in the olfactory tubercle, septum and hypothalamus. The drug decreased dopamine (DA) turnover rate in the caudatus, but did not inhibit tyrosine hydroxylase activity. The drug significantly enhanced stereotyped behavior induced by apomorphine and d-methamphetamine. Clonazepam enhanced apomorphine-induced decrease in striatal HVA, and cortical DOPAC and HVA contents, and d-methamphetamine-induced decrease in cortical DOPAC content. Reserpine pretreatment did not affect apomorphine-induced stereotypy and its enhancement with clonazepam. The drug did not activate adenylate cyclase nor DA-sensitive adenylate cyclase in the striatal homogenates and did not change cyclic AMP content in the caudatus. The drug inhibited phosphodiesterase activity in caudate and cortical homogenates but not in vivo. Clonazepam did not alter ChAc and AChE activities in the caudatus, 6 other cerebral regions and the spinal area. Clonazepam also decreased NE turnover in the caudatus and 5-HIAA contents in the brainstem area. These neurochemical and behavioral effects of clonazepam indicate probable postjunctional DA stimulation in the striatum and cortex of the type not linked with adenylate cyclase and phosphodiesterase but probably due to activation of inhibitory gamma-amino butyric acid (GABA) neurons on the strio-nigral pathway."}
{"id": "PMID:207629", "title": "Deep tendon reflex in Eaton-Lambert syndrome.", "content": "The mechanism of absent or decreased deep tendon reflex in Eaton-Lambert syndrome was studied. There was no evidence suggestive of the presence of a neuropathy. On the other hand, a brief (about 10 seconds) maximal voluntary contraction made the absent deep tendon reflexes elicitable, which suggests that the block of neuromuscular transmission in Eaton-Lambert syndrome is responsible for the absent or decreased deep tendon reflex. Such enhancement of the decreased deep tendon reflex in Eaton-Lambert syndrome might be helpful in differentiating neuropathy and Eaton-Lambert syndrome.", "contents": "Deep tendon reflex in Eaton-Lambert syndrome. The mechanism of absent or decreased deep tendon reflex in Eaton-Lambert syndrome was studied. There was no evidence suggestive of the presence of a neuropathy. On the other hand, a brief (about 10 seconds) maximal voluntary contraction made the absent deep tendon reflexes elicitable, which suggests that the block of neuromuscular transmission in Eaton-Lambert syndrome is responsible for the absent or decreased deep tendon reflex. Such enhancement of the decreased deep tendon reflex in Eaton-Lambert syndrome might be helpful in differentiating neuropathy and Eaton-Lambert syndrome."}
{"id": "PMID:207631", "title": "Effect of ACTH 4-10 on passive avoidance of rats lacking vasopressin (Brattleboro strain).", "content": "The hypothesis that the effects of ACTH 4-10 on avoidance are mediated via the release of endogenous vasopressin was investigated. To test this hypothesis, we observed the effect of ACTH 4-10 on the passive avoidance of Brattleboro rats with diabetes insipidus resulting from a total genetic deficiency of vasopressin (DI) and Brattleboro rats without diabetes insipidus (HE). Normal Long-Evans rats (LE) were also included for comparison purposes. The results did not support the hypothesis. ACTH 4-10 did influence the passive avoidance of DI rats; this should not have occurred if the release of endogenous vasopressin is necessary for ACTH 4-10 to influence avoidance.", "contents": "Effect of ACTH 4-10 on passive avoidance of rats lacking vasopressin (Brattleboro strain). The hypothesis that the effects of ACTH 4-10 on avoidance are mediated via the release of endogenous vasopressin was investigated. To test this hypothesis, we observed the effect of ACTH 4-10 on the passive avoidance of Brattleboro rats with diabetes insipidus resulting from a total genetic deficiency of vasopressin (DI) and Brattleboro rats without diabetes insipidus (HE). Normal Long-Evans rats (LE) were also included for comparison purposes. The results did not support the hypothesis. ACTH 4-10 did influence the passive avoidance of DI rats; this should not have occurred if the release of endogenous vasopressin is necessary for ACTH 4-10 to influence avoidance."}
{"id": "PMID:207632", "title": "Synovial sarcoma of the soft palate: report of a case.", "content": "A case of primary synovial sarcoma of the soft palate is reported in a 19 year old man who was in good health and free of recurrence one year after operation. Radiation therapy was selected and a dose of 7600 rads was given. The presence of hyaluronic acid was investigated using the critical electrolyte concentration method. The tumor was considered histogenetically to be derived from undifferentiated mesenchymal tissue.", "contents": "Synovial sarcoma of the soft palate: report of a case. A case of primary synovial sarcoma of the soft palate is reported in a 19 year old man who was in good health and free of recurrence one year after operation. Radiation therapy was selected and a dose of 7600 rads was given. The presence of hyaluronic acid was investigated using the critical electrolyte concentration method. The tumor was considered histogenetically to be derived from undifferentiated mesenchymal tissue."}
{"id": "PMID:207633", "title": "An unusual multifocal leiomyosarcoma of the stomach: a light and electron microscopic study.", "content": "A multifocal leiomyosarcoma of the stomach originating from the muscularis mucosae with lymph node and distant metastases is described in a 66 year old man. The electron microscopic features of a representative tumor mass and a metastasis confirmed the smooth muscle histogenesis. The light microscopic appearance consistently suggested malignant fibrous histocytoma. The pathological features of gasttric leiomyosarcomas are reviewed with special emphasis on the problem of practical diagnosis. This case also indicates that not all sarcomas with storiform features are necessarily histiocytic in origin.", "contents": "An unusual multifocal leiomyosarcoma of the stomach: a light and electron microscopic study. A multifocal leiomyosarcoma of the stomach originating from the muscularis mucosae with lymph node and distant metastases is described in a 66 year old man. The electron microscopic features of a representative tumor mass and a metastasis confirmed the smooth muscle histogenesis. The light microscopic appearance consistently suggested malignant fibrous histocytoma. The pathological features of gasttric leiomyosarcomas are reviewed with special emphasis on the problem of practical diagnosis. This case also indicates that not all sarcomas with storiform features are necessarily histiocytic in origin."}
{"id": "PMID:207634", "title": "[Rotavirus as a causative agent of infantile gastroenteritis. Diagnosis and epidemiology (author's transl)].", "content": "Some years ago it was not possible in spite of intensive bacteriological and virological work on the etiology of acute infantile gastroenteritis to find any agent that may readily be linked to this disease. Since five years now early sporadic reports about virus-like particles have proved worldwide to be correct and in the meantime have substantially been supported by new findings in that these particles are the main causative agent of infantile gastroenteritis. As part of our electron-microscopic studies some morphological characteristics are shown. The physico-chemical as well as structural properties of the new virus apparently justify its classification into the family of the reoviruses. Rotavirus positive stool specimens were found in 46% of the material sent in by paediatric clinics.", "contents": "[Rotavirus as a causative agent of infantile gastroenteritis. Diagnosis and epidemiology (author's transl)]. Some years ago it was not possible in spite of intensive bacteriological and virological work on the etiology of acute infantile gastroenteritis to find any agent that may readily be linked to this disease. Since five years now early sporadic reports about virus-like particles have proved worldwide to be correct and in the meantime have substantially been supported by new findings in that these particles are the main causative agent of infantile gastroenteritis. As part of our electron-microscopic studies some morphological characteristics are shown. The physico-chemical as well as structural properties of the new virus apparently justify its classification into the family of the reoviruses. Rotavirus positive stool specimens were found in 46% of the material sent in by paediatric clinics."}
{"id": "PMID:207630", "title": "Preliminary studies on the diffusion of bovid herpesvirus 2 in experimentally infected calves.", "content": "This preliminary study on the diffusion of the Bovid herpesvirus 2 (BHV2) in calves inoculated intravenously, allowed to identify the target organs of the virus. In particular, in the first phase of the infection, i.e. post infection day (PID) 2, the virus resulted extensively widespread in the body of the calf, whereas in a subsequent phase, PID6, the virus was recovered only from the skin, the lymph nodes and the nervous system. Finally virus was not recovered in any of the tissues obtained from the calf killed at PID 12. Based on the results it might be speculated that, under the experimental conditions of these tests, the infection of cattle by BHV2 develops through two stages. The first stage would be characterized by a systemic condition in that the virus is present in the whole organism; the second stage which follows, consists in a localized infection, the virus being present only in some districts of the organism (skin, lymph nodes, nervous system) which could be considered as the definitive target sites for virus replication.", "contents": "Preliminary studies on the diffusion of bovid herpesvirus 2 in experimentally infected calves. This preliminary study on the diffusion of the Bovid herpesvirus 2 (BHV2) in calves inoculated intravenously, allowed to identify the target organs of the virus. In particular, in the first phase of the infection, i.e. post infection day (PID) 2, the virus resulted extensively widespread in the body of the calf, whereas in a subsequent phase, PID6, the virus was recovered only from the skin, the lymph nodes and the nervous system. Finally virus was not recovered in any of the tissues obtained from the calf killed at PID 12. Based on the results it might be speculated that, under the experimental conditions of these tests, the infection of cattle by BHV2 develops through two stages. The first stage would be characterized by a systemic condition in that the virus is present in the whole organism; the second stage which follows, consists in a localized infection, the virus being present only in some districts of the organism (skin, lymph nodes, nervous system) which could be considered as the definitive target sites for virus replication."}
{"id": "PMID:207635", "title": "[Structure and function of the eosinophil leucocytes (author's transl)].", "content": "It is well established that eosinophilia both in tissue and in the circulation is characteristic for many clinical conditions. They include diseases associated with immediate and delayed type hypersensitivity. Under these conditions the eosinophil leukocyte is a prominent participant at sites of inflammatory reactions. Through their enzymes they are able to counteract the mediators of inflammation, such as histamine, the slow reacting substance of anaphylaxis (SRS-A) and the platelet aggregating factor (PAF). In addition, eosinophils exert their sepcific functions during parasitic infection, in which they lead to severe damage of parasites. Eosinophils have also been involved in the process of the replenishment of mediators by dampening the synthesis of mediators in mast cells. Accumulation of eosinophils in tissue or in the circulation is due to chemokinesis and chemotaxis. A great number of eosinophilotactic factors can be generated from cells, such as lymphocytes, basophils, mast cells and polymorphnuclear leukocytes. In addition, several serum components have been shown to exert eosinophilotactic properties. The eosinophilotactic factors differ in molecular weight, chemical structure and their specificty. Eosinophilia is therefore a complex phenomenon: It can be modulated by factors which act on the maturation of the eosinophil, on the production and secretion of eosinophilotactic factors and on the responsiveness of the target cells.", "contents": "[Structure and function of the eosinophil leucocytes (author's transl)]. It is well established that eosinophilia both in tissue and in the circulation is characteristic for many clinical conditions. They include diseases associated with immediate and delayed type hypersensitivity. Under these conditions the eosinophil leukocyte is a prominent participant at sites of inflammatory reactions. Through their enzymes they are able to counteract the mediators of inflammation, such as histamine, the slow reacting substance of anaphylaxis (SRS-A) and the platelet aggregating factor (PAF). In addition, eosinophils exert their sepcific functions during parasitic infection, in which they lead to severe damage of parasites. Eosinophils have also been involved in the process of the replenishment of mediators by dampening the synthesis of mediators in mast cells. Accumulation of eosinophils in tissue or in the circulation is due to chemokinesis and chemotaxis. A great number of eosinophilotactic factors can be generated from cells, such as lymphocytes, basophils, mast cells and polymorphnuclear leukocytes. In addition, several serum components have been shown to exert eosinophilotactic properties. The eosinophilotactic factors differ in molecular weight, chemical structure and their specificty. Eosinophilia is therefore a complex phenomenon: It can be modulated by factors which act on the maturation of the eosinophil, on the production and secretion of eosinophilotactic factors and on the responsiveness of the target cells."}
{"id": "PMID:207636", "title": "Cell interaction during lymphocyte activation.", "content": "Adherent cells were separated from stimulated lymphocytes by a layer of agarose to determine the requirement for lymphocyte interaction with adherent cells. The results demonstrated that the presence of plastic adherent cells was obligatory for oxidative activation, but contact of plastic adherent cells with oxidized nonadherent lymphocytes was not. A similar relationship was found to exist between adherent and nonadherent populations during PHA and Con A stimulation. In contrast, the responses of PWM- and ZnCl2-stimulated lymphocytes were not augmented by the presence of adherent cells unless the two populations were in contact.", "contents": "Cell interaction during lymphocyte activation. Adherent cells were separated from stimulated lymphocytes by a layer of agarose to determine the requirement for lymphocyte interaction with adherent cells. The results demonstrated that the presence of plastic adherent cells was obligatory for oxidative activation, but contact of plastic adherent cells with oxidized nonadherent lymphocytes was not. A similar relationship was found to exist between adherent and nonadherent populations during PHA and Con A stimulation. In contrast, the responses of PWM- and ZnCl2-stimulated lymphocytes were not augmented by the presence of adherent cells unless the two populations were in contact."}
{"id": "PMID:207646", "title": "Relationship between Epstein-Barr virus (EBV)-production and the loss of the EBV receptor/complement receptor complex in a series of sublines derived from the same original Burkitt's lymphoma.", "content": "Virus production, EBV (P3HR-1 substrain) superinfectability, IdUrd inducibility, EBV receptor and complement (C3) receptor expression were assessed in two independently maintained jijoye lines, the derived P3HR-1 clone that releases a growth inhibitory and cytopathic, non-transforming viral mutant, and in non-producer sublines derived from the P3HR-1 line by the spontaneous cessation of virus production. Both jijoye lines were superinfectable, inducible, and carried EBV and C3 receptors. Virus-producing P3HR-1 cells and recently derived non-producer sublines lacked EBV-receptors and C3 receptors, could not be superinfected, but were IdUrd inducible. Two long-passaged, non-producer sublines of P3HR-1 reexpressed EBV and C3 receptors to an equal degree (different in the two sublines). EBV-superinfectability became partially reestablished in the subline with the higher expression of EBV and C3 receptors. These findings support the hypothesis that the EBV-receptor/C3 receptor negativity of the producer P3HR-1 sublines and their recent non-producer derivatives is due to negative selection by the growth-inhibitory, cytopathic P3HR-1 virus variant. The closely linked disappearance and reappearance of EBV-receptors and complement receptors gives further support to the idea that these two receptors are either identical or closely linked constituents of the cell membrane.", "contents": "Relationship between Epstein-Barr virus (EBV)-production and the loss of the EBV receptor/complement receptor complex in a series of sublines derived from the same original Burkitt's lymphoma. Virus production, EBV (P3HR-1 substrain) superinfectability, IdUrd inducibility, EBV receptor and complement (C3) receptor expression were assessed in two independently maintained jijoye lines, the derived P3HR-1 clone that releases a growth inhibitory and cytopathic, non-transforming viral mutant, and in non-producer sublines derived from the P3HR-1 line by the spontaneous cessation of virus production. Both jijoye lines were superinfectable, inducible, and carried EBV and C3 receptors. Virus-producing P3HR-1 cells and recently derived non-producer sublines lacked EBV-receptors and C3 receptors, could not be superinfected, but were IdUrd inducible. Two long-passaged, non-producer sublines of P3HR-1 reexpressed EBV and C3 receptors to an equal degree (different in the two sublines). EBV-superinfectability became partially reestablished in the subline with the higher expression of EBV and C3 receptors. These findings support the hypothesis that the EBV-receptor/C3 receptor negativity of the producer P3HR-1 sublines and their recent non-producer derivatives is due to negative selection by the growth-inhibitory, cytopathic P3HR-1 virus variant. The closely linked disappearance and reappearance of EBV-receptors and complement receptors gives further support to the idea that these two receptors are either identical or closely linked constituents of the cell membrane."}
{"id": "PMID:207647", "title": "Active immunization against murine radiation-induced leukemia using a sarcoma virus pseudotype.", "content": "Immunization of C57BL/Ka mice against the radiation leukemia virus (Rad LV) markedly reduced their susceptibility to development of leukemia after X-radiation. The active immunogen used consisted of a sarcoma virus pseudotype of Rad LV which induces regressing sarcomas in young adult mice. These immunized animals were challenged with four weekly 160-rad X-ray exposures. The appearance of lymphomas and leukemias resulting from such irradiation was delayed and their incidence significantly decreased. These results indicate that oncornavirus immunization may be used to reduce the incidence of murine leukemias which are triggered by a physical agent.", "contents": "Active immunization against murine radiation-induced leukemia using a sarcoma virus pseudotype. Immunization of C57BL/Ka mice against the radiation leukemia virus (Rad LV) markedly reduced their susceptibility to development of leukemia after X-radiation. The active immunogen used consisted of a sarcoma virus pseudotype of Rad LV which induces regressing sarcomas in young adult mice. These immunized animals were challenged with four weekly 160-rad X-ray exposures. The appearance of lymphomas and leukemias resulting from such irradiation was delayed and their incidence significantly decreased. These results indicate that oncornavirus immunization may be used to reduce the incidence of murine leukemias which are triggered by a physical agent."}
{"id": "PMID:207648", "title": "Murine Rous-sarcoma-specific immunity detected by leukocyte adherence inhibition: inhibitory effect of normal serum.", "content": "The standard one-stage lymphocyte adherence inhibition (LAI) assay was used to investigate cellular and humoral immune responses within the murine Rous sarcoma system. Significant specific cellular reactivity to Rous sarcoma antigen extracts was detected when the responder peritoneal exudate cells (PEC) were obtained from mice bearing or immunized against primary or transplanted Rous sarcomas; no cellular reactivity to control methylcholanthrene (MC)-induced tumor antigen extracts was observed. Similarly, specific cell-mediated recognition of MC tumor antigen extract was demonstrated. Initial experiments designed to assess the role of serum components in the LAI assay demonstrated that normal mouse serum of C57BL/10ScSn, B10.D2, or A/WySn origin, either fresh or frozen, obtained from old (over 7 months) or young (under 6 weeks) mice non-specifically abrogated the specific loss of PEC adherence.", "contents": "Murine Rous-sarcoma-specific immunity detected by leukocyte adherence inhibition: inhibitory effect of normal serum. The standard one-stage lymphocyte adherence inhibition (LAI) assay was used to investigate cellular and humoral immune responses within the murine Rous sarcoma system. Significant specific cellular reactivity to Rous sarcoma antigen extracts was detected when the responder peritoneal exudate cells (PEC) were obtained from mice bearing or immunized against primary or transplanted Rous sarcomas; no cellular reactivity to control methylcholanthrene (MC)-induced tumor antigen extracts was observed. Similarly, specific cell-mediated recognition of MC tumor antigen extract was demonstrated. Initial experiments designed to assess the role of serum components in the LAI assay demonstrated that normal mouse serum of C57BL/10ScSn, B10.D2, or A/WySn origin, either fresh or frozen, obtained from old (over 7 months) or young (under 6 weeks) mice non-specifically abrogated the specific loss of PEC adherence."}
{"id": "PMID:207649", "title": "Induction of mammary tumors in C57BL/HAAG female mice by a low oncogenic mammary tumor virus.", "content": "Mammary tumor virus (MuMTV)-negative mouse substrain C57BL/Haag foster-nursed by strain DD becomes a line with a moderately high incidence of mammary tumors occurring in the females at a late age. Electron microscopy revealed B particles in the tumors, providing additional evidence for the propagation and transmission of DD-MuMTV in C57BL/HaagfDD. Since both albino strains DD and RIII originated in Europe, develop pregnancy-dependent mammary tumors, carry black and agouti genes (cc, BB, AA), and therefore may be related, evidence is presented which suggests that the two naturally occurring MuMTVs from DD and RIII may also be related, and that they may share a common origin.", "contents": "Induction of mammary tumors in C57BL/HAAG female mice by a low oncogenic mammary tumor virus. Mammary tumor virus (MuMTV)-negative mouse substrain C57BL/Haag foster-nursed by strain DD becomes a line with a moderately high incidence of mammary tumors occurring in the females at a late age. Electron microscopy revealed B particles in the tumors, providing additional evidence for the propagation and transmission of DD-MuMTV in C57BL/HaagfDD. Since both albino strains DD and RIII originated in Europe, develop pregnancy-dependent mammary tumors, carry black and agouti genes (cc, BB, AA), and therefore may be related, evidence is presented which suggests that the two naturally occurring MuMTVs from DD and RIII may also be related, and that they may share a common origin."}
{"id": "PMID:207645", "title": "Cadmium induced changes in the liver of langurs (Presbytis entellus-entellus dufresne).", "content": "1- Cadmium-induced hepatic disturbances in Langurs have been studied following a single low dose administration of the salt (Cd Cl2 4 mg/kg s.c.). 2-Serum transaminases, choelsterol and liver glycogen levels were elevated. Alkaline phosphatase levels were in normal range. The blood sugar was at a low level. 3- Degranulation, vacuolization and distortion of the liver cells and lobules were conspicuous. 4- In conclusion this study would indicate that increased serum enzyme activity and increased plasma choelsterol levels are a manifestation of tissue damage. It would seem plausible to translate these observations in terms of similar infarcts occurring in man.", "contents": "Cadmium induced changes in the liver of langurs (Presbytis entellus-entellus dufresne). 1- Cadmium-induced hepatic disturbances in Langurs have been studied following a single low dose administration of the salt (Cd Cl2 4 mg/kg s.c.). 2-Serum transaminases, choelsterol and liver glycogen levels were elevated. Alkaline phosphatase levels were in normal range. The blood sugar was at a low level. 3- Degranulation, vacuolization and distortion of the liver cells and lobules were conspicuous. 4- In conclusion this study would indicate that increased serum enzyme activity and increased plasma choelsterol levels are a manifestation of tissue damage. It would seem plausible to translate these observations in terms of similar infarcts occurring in man."}
{"id": "PMID:207650", "title": "Lysis of RSV-transformed Japanese quail cells by a factor from normal quail serum.", "content": "Normal sera of Japanese quails caused lysis of tumor cells from a Rous sarcoma virus (RSV)-induced quail tumor (QT cells). Other tumor cell lines, including RSV-transformed quail embryo cells and methylcholanthrene-induced quail tumors, were not lysed. This naturally occurring cytolytic factor (NCLF) was sensitive to heating at 56 degrees C, zymosan, and inulin, and it required magnesium but not calcium for the expression of its activity. These results suggested that NCLF activity was mediated by complement activated through an alternative pathway. This possible complement activation occurred in the absence of specific antibodies to the target cells.", "contents": "Lysis of RSV-transformed Japanese quail cells by a factor from normal quail serum. Normal sera of Japanese quails caused lysis of tumor cells from a Rous sarcoma virus (RSV)-induced quail tumor (QT cells). Other tumor cell lines, including RSV-transformed quail embryo cells and methylcholanthrene-induced quail tumors, were not lysed. This naturally occurring cytolytic factor (NCLF) was sensitive to heating at 56 degrees C, zymosan, and inulin, and it required magnesium but not calcium for the expression of its activity. These results suggested that NCLF activity was mediated by complement activated through an alternative pathway. This possible complement activation occurred in the absence of specific antibodies to the target cells."}
{"id": "PMID:207651", "title": "The radiolysis of glyceraldehyde-3-phosphate dehydrogenase.", "content": "The yields in molecules per 100 eV for active-site and sulphydryl loss from glyceraldehyde-3-phosphate dehydrogenase have been determined in nitrous-oxide-saturated, aerated and argon-saturated solutions. Molecular hydrogen peroxide produces a sulphenic acid product, which can be repaired by post-irradiation treatment with dithiothreitol. Comparison of the yields under various conditions showed that in aerated solutions both .OH and .O2-radicals inactivated the enzyme with an efficiency of about 26 per cent. However, the efficiency of .OH in air-free solutions was less, and inactivation by .H and eaq- did not appear to be appreciable. There is a correlation between SH loss and loss of active sites.", "contents": "The radiolysis of glyceraldehyde-3-phosphate dehydrogenase. The yields in molecules per 100 eV for active-site and sulphydryl loss from glyceraldehyde-3-phosphate dehydrogenase have been determined in nitrous-oxide-saturated, aerated and argon-saturated solutions. Molecular hydrogen peroxide produces a sulphenic acid product, which can be repaired by post-irradiation treatment with dithiothreitol. Comparison of the yields under various conditions showed that in aerated solutions both .OH and .O2-radicals inactivated the enzyme with an efficiency of about 26 per cent. However, the efficiency of .OH in air-free solutions was less, and inactivation by .H and eaq- did not appear to be appreciable. There is a correlation between SH loss and loss of active sites."}
{"id": "PMID:207659", "title": "[Clinial picture and localization of skin metastasis of visceral carcinomas].", "content": "Seven cases with secondary skin carcinomas are described. The primary tumor was located at the tongue, the larynx, the thyroid, the abdomen, the ovaries, the collum uteri and the rectum. From the literature 60 other patients with secundary skin carcinomas and 100 primary carcinomas were evaluated. Clinical evidences for a secundary skin carcinoma are: unusual localization, multiple occurrence and an even surface. It was examined whether the localization of the secundary skin tumor refers to the localization of the primary tumor.", "contents": "[Clinial picture and localization of skin metastasis of visceral carcinomas]. Seven cases with secondary skin carcinomas are described. The primary tumor was located at the tongue, the larynx, the thyroid, the abdomen, the ovaries, the collum uteri and the rectum. From the literature 60 other patients with secundary skin carcinomas and 100 primary carcinomas were evaluated. Clinical evidences for a secundary skin carcinoma are: unusual localization, multiple occurrence and an even surface. It was examined whether the localization of the secundary skin tumor refers to the localization of the primary tumor."}
{"id": "PMID:207657", "title": "Radionuclide imaging of bowel infarction complicating small bowel intussusception in dogs.", "content": "Technetium-99m (99mTc)-pyrophosphate was investigated for use as an indicator of intestinal infarction in intussuscepted bowel. Irreducible intussusceptions were created in eight adult mongrel dogs. Technetium-99m-pyrophosphate was then injected intravenously 24 and 48 hrs later for external scanning. In six of the dogs, infarction developed in the intussusception, and each demonstrated increased uptake of 99mTc-pyrophosphate on in vivo scintiscans. The two dogs without infarction showed no increase uptake of the radionuclide. Well-counting and specimen scanning confirmed increased radionuclide in the infarcted intussusceptions. These observations suggest that 99mTc-pyrophosphate is a reliable indicator of the vascular compromise that sometimes occurs with intestinal intussusception.", "contents": "Radionuclide imaging of bowel infarction complicating small bowel intussusception in dogs. Technetium-99m (99mTc)-pyrophosphate was investigated for use as an indicator of intestinal infarction in intussuscepted bowel. Irreducible intussusceptions were created in eight adult mongrel dogs. Technetium-99m-pyrophosphate was then injected intravenously 24 and 48 hrs later for external scanning. In six of the dogs, infarction developed in the intussusception, and each demonstrated increased uptake of 99mTc-pyrophosphate on in vivo scintiscans. The two dogs without infarction showed no increase uptake of the radionuclide. Well-counting and specimen scanning confirmed increased radionuclide in the infarcted intussusceptions. These observations suggest that 99mTc-pyrophosphate is a reliable indicator of the vascular compromise that sometimes occurs with intestinal intussusception."}
{"id": "PMID:207658", "title": "Heavy-ion radiography: density resolution and specimen radiography.", "content": "Heavy-ion radiography is performed by the passage of a beam of nuclei accelerated to energies of several hundred MeV/nucleon through an object. The technique of recording transmitted nuclei in a downstream stack of plastic sheets affords excellent resolution of density by recording the nuclei only at their stopping points. Imaging of a phantom--which stimulated tumors of low density contrast in a body part--by conventional radiography, computed tomographic scanning and the heavy-ion technique indicated superior density resolution for heavy-ion imaging at radiation dose. Superior imaging of tumors in pathologic specimens was demonstrated for heavy-ion imaging compared to conventional radiography. Values of stopping power for various tumors and normal tissues were determined by a computer-aided technique. Heavy-ion radiography shows promise for superior imaging of low contrast tumors at relatively low radiation low levels.", "contents": "Heavy-ion radiography: density resolution and specimen radiography. Heavy-ion radiography is performed by the passage of a beam of nuclei accelerated to energies of several hundred MeV/nucleon through an object. The technique of recording transmitted nuclei in a downstream stack of plastic sheets affords excellent resolution of density by recording the nuclei only at their stopping points. Imaging of a phantom--which stimulated tumors of low density contrast in a body part--by conventional radiography, computed tomographic scanning and the heavy-ion technique indicated superior density resolution for heavy-ion imaging at radiation dose. Superior imaging of tumors in pathologic specimens was demonstrated for heavy-ion imaging compared to conventional radiography. Values of stopping power for various tumors and normal tissues were determined by a computer-aided technique. Heavy-ion radiography shows promise for superior imaging of low contrast tumors at relatively low radiation low levels."}
{"id": "PMID:207665", "title": "Metabolism of cyclohexane carboxylic acid by Alcaligenes strain W1.", "content": "Thirty-three microorganisms capable of growth with cyclohexane carboxylate as the sole source of carbon were isolated from mud, water, and soil samples from the Aberystwyth area. Preliminary screening and whole-cell oxidation studies suggested that, with one exception, all of the strains metabolized the growth substrate by beta-oxidation of the coenzyme A ester. This single distinctive strain, able to oxidize rapidly trans-4-hydroxycyclohexane carboxylate, 4-ketocyclohexane carboxylate, p-hydroxybenzoate, and protocatechuate when grown with cyclohexane carboxylate, was classified as a strain of Alcaligenes and given the number W1. Enzymes capable of converting cyclohexane carboxylate to p-hydroxybenzoate were induced by growth with the alicyclic acid and included the first unambiguous specimen of a cyclohexane carboxylate hydroxylase. Because it is a very fragile protein, attempts to stabilize the cyclohexane carboxylate hydroxylase so that a purification procedure could be developed have consistently failed. In limited studies with crude cell extracts, we found that hydroxylation occurred at the 4 position, probably yielding the trans isomer of 4-hydroxycyclohexane carboxylate. Simultaneous measurement of oxygen consumption and reduced nicotinamide adenine dinucleotide oxidation, coupled with an assessment of reactant stoichiometry, showed the enzyme to be a mixed-function oxygenase. Mass spectral analysis enabled the conversion of cyclohexane carboxylate to p-hydroxybenzoate by cell extracts to be established unequivocally, and all of our data were consistent with the pathway: cyclohexane carboxylate --> trans-4-hydroxycyclohexane carboxylate --> 4-ketocyclohexane carboxylate --> p-hydroxybenzoate. The further metabolism of p-hydroxybenzoate proceeded by meta fission and by the oxidative branch of the 2-hydroxy-4-carboxymuconic semialde-hyde-cleaving pathway.", "contents": "Metabolism of cyclohexane carboxylic acid by Alcaligenes strain W1. Thirty-three microorganisms capable of growth with cyclohexane carboxylate as the sole source of carbon were isolated from mud, water, and soil samples from the Aberystwyth area. Preliminary screening and whole-cell oxidation studies suggested that, with one exception, all of the strains metabolized the growth substrate by beta-oxidation of the coenzyme A ester. This single distinctive strain, able to oxidize rapidly trans-4-hydroxycyclohexane carboxylate, 4-ketocyclohexane carboxylate, p-hydroxybenzoate, and protocatechuate when grown with cyclohexane carboxylate, was classified as a strain of Alcaligenes and given the number W1. Enzymes capable of converting cyclohexane carboxylate to p-hydroxybenzoate were induced by growth with the alicyclic acid and included the first unambiguous specimen of a cyclohexane carboxylate hydroxylase. Because it is a very fragile protein, attempts to stabilize the cyclohexane carboxylate hydroxylase so that a purification procedure could be developed have consistently failed. In limited studies with crude cell extracts, we found that hydroxylation occurred at the 4 position, probably yielding the trans isomer of 4-hydroxycyclohexane carboxylate. Simultaneous measurement of oxygen consumption and reduced nicotinamide adenine dinucleotide oxidation, coupled with an assessment of reactant stoichiometry, showed the enzyme to be a mixed-function oxygenase. Mass spectral analysis enabled the conversion of cyclohexane carboxylate to p-hydroxybenzoate by cell extracts to be established unequivocally, and all of our data were consistent with the pathway: cyclohexane carboxylate --> trans-4-hydroxycyclohexane carboxylate --> 4-ketocyclohexane carboxylate --> p-hydroxybenzoate. The further metabolism of p-hydroxybenzoate proceeded by meta fission and by the oxidative branch of the 2-hydroxy-4-carboxymuconic semialde-hyde-cleaving pathway."}
{"id": "PMID:207666", "title": "Genetic control of galactokinase synthesis in Saccharomyces cerevisiae: evidence for constitutive expression of the positive regulatory gene gal4.", "content": "Temperature-sensitive (ts) mutants for the gal80 and gal4 genes of Saccharomyces cerevisiae were isolated and characterized. These mutants were classified into two categories; one showed thermolability (TL) and the other showed temperature-sensitive synthesis (TSS) of the respective products. Both the TL and TSS gal80 mutants are constitutive for galactokinase activity at 35 degrees C and, because they are derived from a dominant super-repressible GAL80s mutant, are uninducible at 25 degrees C. Both the TL and TSS gal4 mutants are galactose negative at 35 degrees C and galactose positive at 25 degrees C. None of the ts gal4 mutations affected the thermolability of galactokinase activity in cell extracts. Induction of galactokinase activity was studied with these mutants. The results indicate that the gal80 gene codes for a repressor and the gal4 gene codes for a positive factor indispensable for the expression of the structural genes or their products. However, striking evidence that the expression of the gal4 gene is constitutive and not under the control of gal80 was provided by a kinetic study with the TL gal4 mutant. The TL gal4 mutant pregrown in glycerol nutrient medium at 35 degrees C showed a prolonged lag period (35 min) in the induction of galactokinase activity at 25 degrees C, whereas the same mutant pregrown at 25 degrees C showed the same lag period as those observed in the wild-type strain and a revertant clone derived from the TL gal4 mutant (15 min).", "contents": "Genetic control of galactokinase synthesis in Saccharomyces cerevisiae: evidence for constitutive expression of the positive regulatory gene gal4. Temperature-sensitive (ts) mutants for the gal80 and gal4 genes of Saccharomyces cerevisiae were isolated and characterized. These mutants were classified into two categories; one showed thermolability (TL) and the other showed temperature-sensitive synthesis (TSS) of the respective products. Both the TL and TSS gal80 mutants are constitutive for galactokinase activity at 35 degrees C and, because they are derived from a dominant super-repressible GAL80s mutant, are uninducible at 25 degrees C. Both the TL and TSS gal4 mutants are galactose negative at 35 degrees C and galactose positive at 25 degrees C. None of the ts gal4 mutations affected the thermolability of galactokinase activity in cell extracts. Induction of galactokinase activity was studied with these mutants. The results indicate that the gal80 gene codes for a repressor and the gal4 gene codes for a positive factor indispensable for the expression of the structural genes or their products. However, striking evidence that the expression of the gal4 gene is constitutive and not under the control of gal80 was provided by a kinetic study with the TL gal4 mutant. The TL gal4 mutant pregrown in glycerol nutrient medium at 35 degrees C showed a prolonged lag period (35 min) in the induction of galactokinase activity at 25 degrees C, whereas the same mutant pregrown at 25 degrees C showed the same lag period as those observed in the wild-type strain and a revertant clone derived from the TL gal4 mutant (15 min)."}
{"id": "PMID:207667", "title": "Citrobacter O-antigens: structure of the O-antigenic polysaccharide from Citrobacter sp. 396.", "content": "The structure of the O-specific polysaccharide moiety of the lipopolysaccharide from Citrobacter 396 was elucidated by composition, methylation, and periodate oxidation studies. The repeating unit consists of four 2-linked mannoses and one 3-linked N-acetylglucosamine. One of the mannose units is substituted at C3 with alpha-glucose, and one is substituted at C3 with alpha-(2-O-acetyl)-abequose. All the mannosyl linkages appear to have the beta-configuration; the N-acetylglucosaminyl linkage has the alpha-configuration. In bacterial agglutination and passive hemagglutination in some Salmonella antisera, Citrobacter 396 as well as its O-antigenic lipopolysaccharide expressed the serological factors 5 and 6. In corroboration of our structural studies, this showed the presence of alpha-(2-O-acetyl)-abequosyl-1,3-mannose (factor 5) and alpha-glucosyl-1,3-mannose (factor 6).", "contents": "Citrobacter O-antigens: structure of the O-antigenic polysaccharide from Citrobacter sp. 396. The structure of the O-specific polysaccharide moiety of the lipopolysaccharide from Citrobacter 396 was elucidated by composition, methylation, and periodate oxidation studies. The repeating unit consists of four 2-linked mannoses and one 3-linked N-acetylglucosamine. One of the mannose units is substituted at C3 with alpha-glucose, and one is substituted at C3 with alpha-(2-O-acetyl)-abequose. All the mannosyl linkages appear to have the beta-configuration; the N-acetylglucosaminyl linkage has the alpha-configuration. In bacterial agglutination and passive hemagglutination in some Salmonella antisera, Citrobacter 396 as well as its O-antigenic lipopolysaccharide expressed the serological factors 5 and 6. In corroboration of our structural studies, this showed the presence of alpha-(2-O-acetyl)-abequosyl-1,3-mannose (factor 5) and alpha-glucosyl-1,3-mannose (factor 6)."}
{"id": "PMID:207668", "title": "Acquisition of ability to utilize Xylitol: disadvantages of a constitutive catabolic pathway in Escherichia coli.", "content": "Ribitol+ strains of Escherichia coli acquire the ability to utilize xylitol by mutating to constitutive production of the coordinately controlled ribitol catabolic enzymes ribitol dehydrogenase (RDH) and D-ribulokinase (DRK). Such strains concomitantly acquire toxicity to galacitol and L-arabitol, and to D-arabitol if they are unable to utilize it for growth. Strains selected for resistance to these polyols have DRK structural gene mutations or other mutations that eliminate the constitutive production of DRK, consistent with the view that DRK phosphorylates those polyols to toxic substances. Ribitol+ strains selected for growth on 8 mM xylitol fail to grow on 30 mM xylitol. A product of ribitol and xylitol catabolism represses synthesis of RDH, an enzyme required for growth on xylitol. At 30 mM xylitol, greater than 99% of RDH synthesis is repressed. Strains that grow on 8 mM xylitol can mutate to grow on 30 mM xylitol. Such mutants, relieved of this repression, overproduce RDH, resulting in good growth on the poor substrate, xylitol, but poor growth on the normal substrate, ribitol.", "contents": "Acquisition of ability to utilize Xylitol: disadvantages of a constitutive catabolic pathway in Escherichia coli. Ribitol+ strains of Escherichia coli acquire the ability to utilize xylitol by mutating to constitutive production of the coordinately controlled ribitol catabolic enzymes ribitol dehydrogenase (RDH) and D-ribulokinase (DRK). Such strains concomitantly acquire toxicity to galacitol and L-arabitol, and to D-arabitol if they are unable to utilize it for growth. Strains selected for resistance to these polyols have DRK structural gene mutations or other mutations that eliminate the constitutive production of DRK, consistent with the view that DRK phosphorylates those polyols to toxic substances. Ribitol+ strains selected for growth on 8 mM xylitol fail to grow on 30 mM xylitol. A product of ribitol and xylitol catabolism represses synthesis of RDH, an enzyme required for growth on xylitol. At 30 mM xylitol, greater than 99% of RDH synthesis is repressed. Strains that grow on 8 mM xylitol can mutate to grow on 30 mM xylitol. Such mutants, relieved of this repression, overproduce RDH, resulting in good growth on the poor substrate, xylitol, but poor growth on the normal substrate, ribitol."}
{"id": "PMID:207669", "title": "Arginine auxotrophic phenotype of mutation in pyrA of Salmonella typhimurium: role of N-acetylornithine in the maturation of mutant carbamylphosphate synthetase.", "content": "Mutations in pyrA that abolish catalytic activity of carbamylphosphate synthetase cause auxotrophy for both arginine and a pyrimidine. Eight pyrA mutants auxotrophic only for arginine (AUX) were isolated by the mutagenized phage technique; three of these required arginine only at low temperature (20 degrees C). Explanations of the AUX phenotype based on bradytrophy were eliminated by the discovery that blocking the utilization of carbamylphosphate for pyrimidine biosynthesis by insertion of an additional mutation in pyrB (encoding aspartic transcarbamylase) did not reduce the requirement for arginine. In contrast, mutational blocks in the arginine biosynthetic pathway before N-acetylornithine (argB, argC, argG, or argH) did suppress the mutation in pyrA. This suggests that exogenous arginine permits growth of the AUX mutants by inhibiting the first step in the arginine pathway, thereby preventing accumulation of an intermediate that antagonizes mutant pyrA function. A mutation in argA (N-acetylornithinase) failed to suppress AUX, indicating that N-acetylornithine was the inhibitory intermediate. This intermediate had no effect on the catalytic or regulatory properties of carbamylphosphate synthetase from mutant cells grown under permissive conditions (37 degrees C). However, the regulatory properties of carbamylphosphate synthetase synthesized under restrictive conditions (20 degrees C) were demonstrably defective (insensitive to activation by ornithine); the enzyme synthesized under permissive conditions was activated by ornithine. A strain carrying an additional mutation (argC), which prevents the accumulation of N-acetylornithine, produced an ornithine-activatable enzyme at both growth temperatures. These results suggest that N-acetylornithine antagonizes the proper preconditioning or maturation of the mutant carbamylphosphate synthetase.", "contents": "Arginine auxotrophic phenotype of mutation in pyrA of Salmonella typhimurium: role of N-acetylornithine in the maturation of mutant carbamylphosphate synthetase. Mutations in pyrA that abolish catalytic activity of carbamylphosphate synthetase cause auxotrophy for both arginine and a pyrimidine. Eight pyrA mutants auxotrophic only for arginine (AUX) were isolated by the mutagenized phage technique; three of these required arginine only at low temperature (20 degrees C). Explanations of the AUX phenotype based on bradytrophy were eliminated by the discovery that blocking the utilization of carbamylphosphate for pyrimidine biosynthesis by insertion of an additional mutation in pyrB (encoding aspartic transcarbamylase) did not reduce the requirement for arginine. In contrast, mutational blocks in the arginine biosynthetic pathway before N-acetylornithine (argB, argC, argG, or argH) did suppress the mutation in pyrA. This suggests that exogenous arginine permits growth of the AUX mutants by inhibiting the first step in the arginine pathway, thereby preventing accumulation of an intermediate that antagonizes mutant pyrA function. A mutation in argA (N-acetylornithinase) failed to suppress AUX, indicating that N-acetylornithine was the inhibitory intermediate. This intermediate had no effect on the catalytic or regulatory properties of carbamylphosphate synthetase from mutant cells grown under permissive conditions (37 degrees C). However, the regulatory properties of carbamylphosphate synthetase synthesized under restrictive conditions (20 degrees C) were demonstrably defective (insensitive to activation by ornithine); the enzyme synthesized under permissive conditions was activated by ornithine. A strain carrying an additional mutation (argC), which prevents the accumulation of N-acetylornithine, produced an ornithine-activatable enzyme at both growth temperatures. These results suggest that N-acetylornithine antagonizes the proper preconditioning or maturation of the mutant carbamylphosphate synthetase."}
{"id": "PMID:207670", "title": "Effects of selected inhibitors on electron transport in Neisseria gonorrhoeae.", "content": "The electron transport system of Neisseria gonorrhoeae was partially characterized by using spectrophotometric, spectroscopic, and oxygen consumption measurements. The effects of selected electron transport inhibitors (amytal, rotenone, 2-heptyl-4-hydroxyquinoline, antimycin A1, and potassium cyanide [KCN]) on electron transfer in whole-cell and sonically treated whole-cell preparations of N. gonorrhoeae were examined. The oxidation of reduced nicotinamide adenine dinucleotide, measured as a decrease in absorbance at 340 nm, was inhibited by each of the compounds tested. Oxygen consumption stimulated by reduced nicotinamide adenine dinucleotide was also inhibited, whereas oxygen uptake stimulated by succinate and malate was inhibited by KCN alone, suggesting the presence of a KCN-sensitive terminal oxidase. Room temperature optical difference spectra indicate an operational electron bypass around the amytal-rotenone-binding site. Difference spectra in the presence of 2-heptyl-4-hydroxyquinoline suggest a possible site of interaction of this compound at the substrate side of cytochrome b. Reduced-minus-oxidized spectra of ascorbate-tetramethyl-p-phenylenediamine suggest the participation of b-, a-, and d-type cytochromes in terminal oxidase activity. Hence, N. gonorrhoeae appears to have an electron transport chain containing cytochrome c, two b-type cytochromes (one of which has an oxidase function), and possibly a- and d-type cytochromes. An abbreviated chain exists through which succinate and malate can be oxidized directly by a KCN-sensitive component.", "contents": "Effects of selected inhibitors on electron transport in Neisseria gonorrhoeae. The electron transport system of Neisseria gonorrhoeae was partially characterized by using spectrophotometric, spectroscopic, and oxygen consumption measurements. The effects of selected electron transport inhibitors (amytal, rotenone, 2-heptyl-4-hydroxyquinoline, antimycin A1, and potassium cyanide [KCN]) on electron transfer in whole-cell and sonically treated whole-cell preparations of N. gonorrhoeae were examined. The oxidation of reduced nicotinamide adenine dinucleotide, measured as a decrease in absorbance at 340 nm, was inhibited by each of the compounds tested. Oxygen consumption stimulated by reduced nicotinamide adenine dinucleotide was also inhibited, whereas oxygen uptake stimulated by succinate and malate was inhibited by KCN alone, suggesting the presence of a KCN-sensitive terminal oxidase. Room temperature optical difference spectra indicate an operational electron bypass around the amytal-rotenone-binding site. Difference spectra in the presence of 2-heptyl-4-hydroxyquinoline suggest a possible site of interaction of this compound at the substrate side of cytochrome b. Reduced-minus-oxidized spectra of ascorbate-tetramethyl-p-phenylenediamine suggest the participation of b-, a-, and d-type cytochromes in terminal oxidase activity. Hence, N. gonorrhoeae appears to have an electron transport chain containing cytochrome c, two b-type cytochromes (one of which has an oxidase function), and possibly a- and d-type cytochromes. An abbreviated chain exists through which succinate and malate can be oxidized directly by a KCN-sensitive component."}
{"id": "PMID:207671", "title": "Reduction of ferric iron by L-lactate and DL-glycerol-3-phosphate in membrane preparations from Staphylococcus aureus and interactions with the nitrate reductase system.", "content": "Membrane fractions with L-lactate dehydrogenase, sn-glycerol-3-phosphate (G3P) dehydrogenase, and nitrate reductase activities were prepared from Staphylococcus aureus wild-type and hem mutant strains. These preparations reduced ferric to ferrous iron with L-lactate or G3P as the source of reductant, using ferrozine to trap the ferrous iron. Reduction of ferric iron was insensitive to 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) with either L-lactate or G3P as reductant, but oxalate and dicumarol inhibited reduction with L-lactate as substrate. The membranes had L-lactate- and G3P-nitrate reductase activities, which were inhibited by azide and by HQNO. Reduction of ferric iron under anaerobic conditions was inhibited by nitrate with preparations from the wild-type strain. This effect of nitrate was abolished by blocking electron transport to the nitrate reductase system with azide or HQNO. Nitrate did not inhibit reduction of ferric iron in heme-depleted membranes from the hem mutant unless hemin was added to restore L-lactate- and G3P-nitrate reductase activity. We conclude that reduced components of the electron transport chain that precede cytochrome b serve as the source of reductant for ferric iron and that these components are oxidized preferentially by a functional nitrate reductase system.", "contents": "Reduction of ferric iron by L-lactate and DL-glycerol-3-phosphate in membrane preparations from Staphylococcus aureus and interactions with the nitrate reductase system. Membrane fractions with L-lactate dehydrogenase, sn-glycerol-3-phosphate (G3P) dehydrogenase, and nitrate reductase activities were prepared from Staphylococcus aureus wild-type and hem mutant strains. These preparations reduced ferric to ferrous iron with L-lactate or G3P as the source of reductant, using ferrozine to trap the ferrous iron. Reduction of ferric iron was insensitive to 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) with either L-lactate or G3P as reductant, but oxalate and dicumarol inhibited reduction with L-lactate as substrate. The membranes had L-lactate- and G3P-nitrate reductase activities, which were inhibited by azide and by HQNO. Reduction of ferric iron under anaerobic conditions was inhibited by nitrate with preparations from the wild-type strain. This effect of nitrate was abolished by blocking electron transport to the nitrate reductase system with azide or HQNO. Nitrate did not inhibit reduction of ferric iron in heme-depleted membranes from the hem mutant unless hemin was added to restore L-lactate- and G3P-nitrate reductase activity. We conclude that reduced components of the electron transport chain that precede cytochrome b serve as the source of reductant for ferric iron and that these components are oxidized preferentially by a functional nitrate reductase system."}
{"id": "PMID:207672", "title": "Regulated expression by readthrough translation from a plasmid-encoded beta-galactosidase.", "content": "We have characterized expression of beta-galactosidase from a plasmid cloning vehicle, pBGP120, which carries most of the lacZ gene and contains a single EcoRI site near the end of lacZ. In addition, we have examined expression of heterologous DNA inserted at the position of the EcoRI site. The EcoRI site was shown to be within the sequence coding for beta-galactosidase and its precise location and phase were deduced. Insertion of heterologous EcoRI-generated DNA fragments altered the molecular weight of the plasmid-encoded beta-galactosidase polypeptide. Those insertions that were in the correct phase were expressed at a high level as a fused protein. The different forms of beta-galactosidase polypeptides produced by various hybrid plasmids were all stable proteins. The level of expression of the plasmid-encoded beta-galactosidase was several times higher than maximal expression of chromosome-encoded beta-galactosidase, suggesting that expression is proportional to gene copy number. The expression of the plasmid lacZ gene was controlled by cyclic AMP. When grown in a cya strain (DG74), expression was dependent on exogenous cyclic AMP. Although in normal strains there was insufficient lac repressor to inactivate all copies of the plasmid, repressor regulation was restored when the plasmid was grown in a strain (M96) that overproduces the lac repressor.", "contents": "Regulated expression by readthrough translation from a plasmid-encoded beta-galactosidase. We have characterized expression of beta-galactosidase from a plasmid cloning vehicle, pBGP120, which carries most of the lacZ gene and contains a single EcoRI site near the end of lacZ. In addition, we have examined expression of heterologous DNA inserted at the position of the EcoRI site. The EcoRI site was shown to be within the sequence coding for beta-galactosidase and its precise location and phase were deduced. Insertion of heterologous EcoRI-generated DNA fragments altered the molecular weight of the plasmid-encoded beta-galactosidase polypeptide. Those insertions that were in the correct phase were expressed at a high level as a fused protein. The different forms of beta-galactosidase polypeptides produced by various hybrid plasmids were all stable proteins. The level of expression of the plasmid-encoded beta-galactosidase was several times higher than maximal expression of chromosome-encoded beta-galactosidase, suggesting that expression is proportional to gene copy number. The expression of the plasmid lacZ gene was controlled by cyclic AMP. When grown in a cya strain (DG74), expression was dependent on exogenous cyclic AMP. Although in normal strains there was insufficient lac repressor to inactivate all copies of the plasmid, repressor regulation was restored when the plasmid was grown in a strain (M96) that overproduces the lac repressor."}
{"id": "PMID:207673", "title": "Outgrowth and vegetative growth inhibition of Bacillus subtilis spores after transient exposure to polymyxin B.", "content": "Polymyxin B combined with the resting spores of Bacillus subtilis and inhibited outgrowth and vegetative growth after germination. The antibiotic was released from the resting spores and its inhibitory action was reversed by the addition of di- and trivalent metallic cations.", "contents": "Outgrowth and vegetative growth inhibition of Bacillus subtilis spores after transient exposure to polymyxin B. Polymyxin B combined with the resting spores of Bacillus subtilis and inhibited outgrowth and vegetative growth after germination. The antibiotic was released from the resting spores and its inhibitory action was reversed by the addition of di- and trivalent metallic cations."}
{"id": "PMID:207674", "title": "Regulation of cyclic AMP levels in Arthrobacter crystallopoietes and a morphogenetic mutant.", "content": "The extracellular levels of cyclic AMP (cAMP), cAMP phosphodiesterase activity, and adenylate cyclase activity were measured at various intervals during growth and morphogenesis of Arthrobacter crystallopoietes. There was a significant rise in the extracellular cAMP level at the onset of stationary phase, and this rise coincided with a decrease in intracellular cAMP. The phosphodiesterase activity measured in vitro increased in the early exponential phase of growth as intracellular cAMP decreased, and, conversely, prior to the onset of stationary phase the phosphodiesterase activity decreased as the intracellular cAMP levels increased. Adenylate cyclase activity was greater in cell extracts prepared from cells grown in a medium where morphogenesis was observed. Pyruvate stimulated adenylate cyclase activity in vitro. A morphogenetic mutant, able to grow only as spheres in all media tested, was shown to have altered adenylated cyclase activity, whereas no significant difference compared to the parent strain was detectable in either the phosphodiesterase activity or the levels of extracellular cAMP. The roles of the two enzymes, adenylate cyclase and phosphodiesterase, and excretion of cAMP are discussed with regard to regulation of intracellular cAMP levels and morphogenesis.", "contents": "Regulation of cyclic AMP levels in Arthrobacter crystallopoietes and a morphogenetic mutant. The extracellular levels of cyclic AMP (cAMP), cAMP phosphodiesterase activity, and adenylate cyclase activity were measured at various intervals during growth and morphogenesis of Arthrobacter crystallopoietes. There was a significant rise in the extracellular cAMP level at the onset of stationary phase, and this rise coincided with a decrease in intracellular cAMP. The phosphodiesterase activity measured in vitro increased in the early exponential phase of growth as intracellular cAMP decreased, and, conversely, prior to the onset of stationary phase the phosphodiesterase activity decreased as the intracellular cAMP levels increased. Adenylate cyclase activity was greater in cell extracts prepared from cells grown in a medium where morphogenesis was observed. Pyruvate stimulated adenylate cyclase activity in vitro. A morphogenetic mutant, able to grow only as spheres in all media tested, was shown to have altered adenylated cyclase activity, whereas no significant difference compared to the parent strain was detectable in either the phosphodiesterase activity or the levels of extracellular cAMP. The roles of the two enzymes, adenylate cyclase and phosphodiesterase, and excretion of cAMP are discussed with regard to regulation of intracellular cAMP levels and morphogenesis."}
{"id": "PMID:207675", "title": "Enzymes of purine metabolism in Mycoplasma mycoides subsp. mycoides.", "content": "The major pathways of ribonucleotide biosynthesis in Mycoplasma mycoides subsp. mycoides were proposed previously from studies of its usage of radioactive purines and pyrimidines. To interpret more fully the pattern of purine usage, we have assayed cell-free extracts of this organism for several enzymes associated with the salvage synthesis of purine nucleotides. M. mycoides possessed phosphoribosyltransferases for adenine, guanine, and hypoxanthine, purine nucleoside phosphorylase, GMP reductase, GMP kinase, adenylosuccinate synthetase, and adenylosuccinate lyase. Purine nucleoside kinase and adenosine deaminase were not detected. Examination of kinetic properties and regulation of some of the above enzymes revealed differences between M. mycoides and Escherichia coli. Most notable of these were the greater susceptibility of the enzymes from M. mycoides to inhibition by nucleotides and the more widespread involvement of GMP as an inhibitor. Observations on enzyme activities in vitro allow an adequate explanation of the capacity of guanine to provide M. mycoides with its full requirement for purine nucleotides.", "contents": "Enzymes of purine metabolism in Mycoplasma mycoides subsp. mycoides. The major pathways of ribonucleotide biosynthesis in Mycoplasma mycoides subsp. mycoides were proposed previously from studies of its usage of radioactive purines and pyrimidines. To interpret more fully the pattern of purine usage, we have assayed cell-free extracts of this organism for several enzymes associated with the salvage synthesis of purine nucleotides. M. mycoides possessed phosphoribosyltransferases for adenine, guanine, and hypoxanthine, purine nucleoside phosphorylase, GMP reductase, GMP kinase, adenylosuccinate synthetase, and adenylosuccinate lyase. Purine nucleoside kinase and adenosine deaminase were not detected. Examination of kinetic properties and regulation of some of the above enzymes revealed differences between M. mycoides and Escherichia coli. Most notable of these were the greater susceptibility of the enzymes from M. mycoides to inhibition by nucleotides and the more widespread involvement of GMP as an inhibitor. Observations on enzyme activities in vitro allow an adequate explanation of the capacity of guanine to provide M. mycoides with its full requirement for purine nucleotides."}
{"id": "PMID:207676", "title": "Effect of substitution of monovalent anions in external medium on the swimming pattern of Salmonella typhimurium.", "content": "The effect of replacement of ions in the extracellular medium on the swimming pattern of bacteria (Salmonella typhimurium) has been investigated. The replacement of chloride ion (Cl-) in the standard medium by methanesulfonate ion (MS-) or by propionate ion (Pr-) induced an increase in the tumbling frequency, or a decrease of the end-to-end distances of tracks. Replacement of MS- by Cl- resulted in transient depression of tumbling, and replacement of Pr- by Cl- resulted in immediate recovery of normal swimming. The replacement of cations was not very effective. The experimental data, including the dependence of the effect of replacement on the ion concentration, are consistent with the ideas that the tumbling frequency increases with depolarization of the bacterial membrane and that such anions as MS- and Pr- are more able to permeate the membrane than is Cl-.", "contents": "Effect of substitution of monovalent anions in external medium on the swimming pattern of Salmonella typhimurium. The effect of replacement of ions in the extracellular medium on the swimming pattern of bacteria (Salmonella typhimurium) has been investigated. The replacement of chloride ion (Cl-) in the standard medium by methanesulfonate ion (MS-) or by propionate ion (Pr-) induced an increase in the tumbling frequency, or a decrease of the end-to-end distances of tracks. Replacement of MS- by Cl- resulted in transient depression of tumbling, and replacement of Pr- by Cl- resulted in immediate recovery of normal swimming. The replacement of cations was not very effective. The experimental data, including the dependence of the effect of replacement on the ion concentration, are consistent with the ideas that the tumbling frequency increases with depolarization of the bacterial membrane and that such anions as MS- and Pr- are more able to permeate the membrane than is Cl-."}
{"id": "PMID:207677", "title": "Reduction of nicotinamide adenine dinucleotide by pyruvate:lipoate oxidoreductase in anaerobic, dark-grown Rhodospirillum rubrum mutant C.", "content": "Cell extracts from fermentatively grown Rhodospirillum rubrum reduced about 80 nmol of nicotinamide adenine dinucleotide (NAD) per mg of protein per min under anaerobic conditions with sodium pyruvate. The reaction was specific for pyruvate and NAD; NAD phosphate was not reduced. Results indicated that pyruvate-linked NAD reduction occurred via pyruvate:lipoate oxidoreductase. The reaction required catalytic amounts of both coenzyme A and thiamine pyrophosphate. Addition of sodium arsenite inhibited enzyme activity by 90%. Pyruvate:lipoate oxidoreductase was the only system detected in anaerobic, dark-grown R. rubrum cell extracts which operated to produce reduced NAD. The low activity of the enzyme system suggested that it was not quantitatively important in ATP formation.", "contents": "Reduction of nicotinamide adenine dinucleotide by pyruvate:lipoate oxidoreductase in anaerobic, dark-grown Rhodospirillum rubrum mutant C. Cell extracts from fermentatively grown Rhodospirillum rubrum reduced about 80 nmol of nicotinamide adenine dinucleotide (NAD) per mg of protein per min under anaerobic conditions with sodium pyruvate. The reaction was specific for pyruvate and NAD; NAD phosphate was not reduced. Results indicated that pyruvate-linked NAD reduction occurred via pyruvate:lipoate oxidoreductase. The reaction required catalytic amounts of both coenzyme A and thiamine pyrophosphate. Addition of sodium arsenite inhibited enzyme activity by 90%. Pyruvate:lipoate oxidoreductase was the only system detected in anaerobic, dark-grown R. rubrum cell extracts which operated to produce reduced NAD. The low activity of the enzyme system suggested that it was not quantitatively important in ATP formation."}
{"id": "PMID:207678", "title": "Acetate kinase production by Escherichia coli during steady-state and transient growth in continuous culture.", "content": "The synthesis of acetate kinase by Escherichia coli ATCC 9637 was studied during growth in anaerobic continuous cultures under steady-state and transient conditions. During growth in anaerobic, glucose-limited chemostats, acetate kinase synthesis was linearly associated with growth. Two types of non-steady-state transients were studied: the perturbation in one was the addition of glucose alone, and, in the second, glucose plus Casamino Acids. During the nutritional shift-up in the second case, but not in the first, the instantaneous specific acetate kinase activities and specific synthesis rates exceeded pre- and postshift values. Trajectory curves demonstrated that the increase in specific activity remained within the bounds of values obtainable under steady-state conditions with minimal and Casamino Acids media. Specific synthesis rates, however, greatly exceeded steady-state values. Enzyme yield values on glucose after the transient nutritional shift-up increased up to fivefold. Active protein synthesis is shown to be necessary to achieve the enhanced specific synthesis rates and enzyme yields. The results from these transient responses are discussed in terms of a conceptful model for metabolic regulation.", "contents": "Acetate kinase production by Escherichia coli during steady-state and transient growth in continuous culture. The synthesis of acetate kinase by Escherichia coli ATCC 9637 was studied during growth in anaerobic continuous cultures under steady-state and transient conditions. During growth in anaerobic, glucose-limited chemostats, acetate kinase synthesis was linearly associated with growth. Two types of non-steady-state transients were studied: the perturbation in one was the addition of glucose alone, and, in the second, glucose plus Casamino Acids. During the nutritional shift-up in the second case, but not in the first, the instantaneous specific acetate kinase activities and specific synthesis rates exceeded pre- and postshift values. Trajectory curves demonstrated that the increase in specific activity remained within the bounds of values obtainable under steady-state conditions with minimal and Casamino Acids media. Specific synthesis rates, however, greatly exceeded steady-state values. Enzyme yield values on glucose after the transient nutritional shift-up increased up to fivefold. Active protein synthesis is shown to be necessary to achieve the enhanced specific synthesis rates and enzyme yields. The results from these transient responses are discussed in terms of a conceptful model for metabolic regulation."}
{"id": "PMID:207679", "title": "Some recent biochemical findings with possible therapeutic implications for schizophrenia.", "content": "Hemodialysis resulted in remission of psychopathological symptoms in eight of ten chronic schizophrenics and successful hemodialysis was associated with a decrease of leucine endorphin levels in the blood. Three endorphins (endogenous peptides) have been isolated from the brain, and among them beta-endorphin was found to be the most potent in inducing behavioral changes in the rat. Nevertheless, neither a positive, nor an inverse relationship between the severity of schizophrenic psychopathology and CSF endorphin concentrations could be borne out by clinical experiments. Most recently, on the basis of an entirely different line of research, the possibility that schizophrenia is a prostaglandin deficiency disease has been raised.", "contents": "Some recent biochemical findings with possible therapeutic implications for schizophrenia. Hemodialysis resulted in remission of psychopathological symptoms in eight of ten chronic schizophrenics and successful hemodialysis was associated with a decrease of leucine endorphin levels in the blood. Three endorphins (endogenous peptides) have been isolated from the brain, and among them beta-endorphin was found to be the most potent in inducing behavioral changes in the rat. Nevertheless, neither a positive, nor an inverse relationship between the severity of schizophrenic psychopathology and CSF endorphin concentrations could be borne out by clinical experiments. Most recently, on the basis of an entirely different line of research, the possibility that schizophrenia is a prostaglandin deficiency disease has been raised."}
{"id": "PMID:207680", "title": "Sleep patterns in three acute combat fatigue cases.", "content": "A preliminary report is presented on the sleep patterns of three combat fatigued patients with recurrent nightmares, insomnia, low frustration thresholds and impotence. All the patients had undergone acute partial sleep deprivation prior to their breakdown. The results show severe deficiency in REM sleep and absence of stage 4 sleep. EMG was usually high with numerous body movements and bursts of tachycardia throughout the night. Nightmares occurred in stage 2. Total effective sleep time was between 129' and 250'. Most of the sleep was in stage 2, and patients woke up with the feeling that \"they had not slept at all.\" It is hypothesized that acute partial sleep deprivation prior to breakdown was an important predisposing factor, and that chronic partial sleep deprivation was a constant aggravating factor of combat fatigue. Replacement therapy for the specific deficient sleep states is proposed.", "contents": "Sleep patterns in three acute combat fatigue cases. A preliminary report is presented on the sleep patterns of three combat fatigued patients with recurrent nightmares, insomnia, low frustration thresholds and impotence. All the patients had undergone acute partial sleep deprivation prior to their breakdown. The results show severe deficiency in REM sleep and absence of stage 4 sleep. EMG was usually high with numerous body movements and bursts of tachycardia throughout the night. Nightmares occurred in stage 2. Total effective sleep time was between 129' and 250'. Most of the sleep was in stage 2, and patients woke up with the feeling that \"they had not slept at all.\" It is hypothesized that acute partial sleep deprivation prior to breakdown was an important predisposing factor, and that chronic partial sleep deprivation was a constant aggravating factor of combat fatigue. Replacement therapy for the specific deficient sleep states is proposed."}
{"id": "PMID:207681", "title": "Biochemical studies on rat liver Golgi apparatus. II. Further characterization of isolated Golgi fraction.", "content": "Although the preparation of rat liver Golgi apparatus isolated by our method contains appreciable activities of NADH- and NADPH-cytochrome c reductases and glucose-6-phosphatase, these enzymes as well as thiamine pyrophosphatase of the extensively fragmented Golgi fraction are partitioned in aqueous polymer two-phase systems quite differently from those associated with microsomes. Similarly, the partition patterns of acid phosphatase and 5'-nucleotidase of the Golgi fragments differ from those of homogenized lysosomes and plasma membrane, respectively. It is concluded that most, if not all, of these marker enzymes in the Golgi fraction cannot be ascribed to contamination by the non-Golgi organelles. In sucrose density gradient centrifugation the NADH- and NADPH-cytochrome c reductase activities of the Golgi fraction behave identically with galactosyltransferase but differently from the reductase activities of microsomes, again indicating that the reductases are inherently associated with the Golgi apparatus. NADPH-cytochrome c reductase of the Golgi preparation is immunologically identical with that of microsomes. The marker enzymes mentioned above and galactosyltransferase behave differently from one another when the Golgi fragments are subjected to partitioning in aqueous polymer two-phase systems, suggesting that these enzymes are not uniformly distributed in the Golgi apparatus structure.", "contents": "Biochemical studies on rat liver Golgi apparatus. II. Further characterization of isolated Golgi fraction. Although the preparation of rat liver Golgi apparatus isolated by our method contains appreciable activities of NADH- and NADPH-cytochrome c reductases and glucose-6-phosphatase, these enzymes as well as thiamine pyrophosphatase of the extensively fragmented Golgi fraction are partitioned in aqueous polymer two-phase systems quite differently from those associated with microsomes. Similarly, the partition patterns of acid phosphatase and 5'-nucleotidase of the Golgi fragments differ from those of homogenized lysosomes and plasma membrane, respectively. It is concluded that most, if not all, of these marker enzymes in the Golgi fraction cannot be ascribed to contamination by the non-Golgi organelles. In sucrose density gradient centrifugation the NADH- and NADPH-cytochrome c reductase activities of the Golgi fraction behave identically with galactosyltransferase but differently from the reductase activities of microsomes, again indicating that the reductases are inherently associated with the Golgi apparatus. NADPH-cytochrome c reductase of the Golgi preparation is immunologically identical with that of microsomes. The marker enzymes mentioned above and galactosyltransferase behave differently from one another when the Golgi fragments are subjected to partitioning in aqueous polymer two-phase systems, suggesting that these enzymes are not uniformly distributed in the Golgi apparatus structure."}
{"id": "PMID:207682", "title": "Purification and characterization of alkaline phosphatase from cultured rat ascites hepatoma cells.", "content": "Alkaline phosphatase of cultured rat ascites hepatoma cells has been purified by butanol extraction, DEAE-cellulose column chromatography, gel filtration through Sephadex G-200, concanavalin A-Sepharose affinity chromatography, and polyacrylamide gel electrophoresis. Affinity chromatography confirmed the glycoprotein nature of alkaline phosphatase from cultured rat ascites hepatoma cells. Electrophoresis on polyacrylamide gels of various concentrations indicated a molecular weight of 290,000. The molecular weight of the subunit was estimated to be 72,000 by SDS-polyacrylamide gel electrophoresis. These findings suggest that alkaline phosphatase of cultured rat ascites hepatoma cells is a tetramer with a subunit molecular weight of 72,000.", "contents": "Purification and characterization of alkaline phosphatase from cultured rat ascites hepatoma cells. Alkaline phosphatase of cultured rat ascites hepatoma cells has been purified by butanol extraction, DEAE-cellulose column chromatography, gel filtration through Sephadex G-200, concanavalin A-Sepharose affinity chromatography, and polyacrylamide gel electrophoresis. Affinity chromatography confirmed the glycoprotein nature of alkaline phosphatase from cultured rat ascites hepatoma cells. Electrophoresis on polyacrylamide gels of various concentrations indicated a molecular weight of 290,000. The molecular weight of the subunit was estimated to be 72,000 by SDS-polyacrylamide gel electrophoresis. These findings suggest that alkaline phosphatase of cultured rat ascites hepatoma cells is a tetramer with a subunit molecular weight of 72,000."}
{"id": "PMID:207683", "title": "Asymmetric permeability of the membrane of egg phosphatidylcholine-cholesterol vesicles to 2,2,6,6 tetramethyl piperidinyl-l-oxycholine.", "content": "The rates of uptake and release of 2,2,6,6 tetramethyl piperidinyl-l-oxycholine (Tempo-choline) for vesicles made of dipalmitoyl phosphatidylcholine (DPPC) and of egg phosphatidylcholine-cholesterol mixtures were measured by ESR and found to have interesting temperature-dependences. In the former case, both rates exhibit a sharp maximum at the critical temperature of phase transition of the bilayer membrane. In the latter case, the permeability of the membrane to Tempo-choline is asymmetric with respect to uptake and release: uptake is appreciable at temperatures higher than 66 degrees C, while release is observable only at temperatures higher than 80 degrees C. The asymmetric permeability is explained in terms of the asymmetric distribution of cholesterol between the outer and inner membranes of the vesicle.", "contents": "Asymmetric permeability of the membrane of egg phosphatidylcholine-cholesterol vesicles to 2,2,6,6 tetramethyl piperidinyl-l-oxycholine. The rates of uptake and release of 2,2,6,6 tetramethyl piperidinyl-l-oxycholine (Tempo-choline) for vesicles made of dipalmitoyl phosphatidylcholine (DPPC) and of egg phosphatidylcholine-cholesterol mixtures were measured by ESR and found to have interesting temperature-dependences. In the former case, both rates exhibit a sharp maximum at the critical temperature of phase transition of the bilayer membrane. In the latter case, the permeability of the membrane to Tempo-choline is asymmetric with respect to uptake and release: uptake is appreciable at temperatures higher than 66 degrees C, while release is observable only at temperatures higher than 80 degrees C. The asymmetric permeability is explained in terms of the asymmetric distribution of cholesterol between the outer and inner membranes of the vesicle."}
{"id": "PMID:207684", "title": "Transient repression of beta-galactosidase synthesis by glucose-6-phosphate in a mutant of Escherichia coli lacking enzyme II specific for glucose in the phosphoenolpyruvate-sugar phosphotransferase system.", "content": "The effects of glucose and glucose-6-phosphate in initiating the repression of beta-galactosidase synthesis were studied using a mutant of Escherichia coli K12 which lacks glucose-specific enzyme II of the phosphoenolpyruvate-sugar phosphotransferase system. It was found that glucose-6-phosphate causes transient repression of beta-galactosidase synthesis but glucose does not cause transient repression in this mutant. Evidence was obtained that both the presence of an active transport system for glucose-6-phosphate in the cells and glucose-6-phosphate in the medium are necessary for the initiation of transient repression. No metabolism of glucose-6-phosphate is required. Upon depletion of glucose-6-phosphate in the medium the transient repression was reversed. After the reversal the rate of enzyme synthesis was high in the cells which had been exposed to a high concentration of glucose-6-phosphate. It was concluded that the translocation of glucose-6-phosphate across the membranes is the primary event which affects both the initiation of and the recovery from the transient repression. During the transient repression the cellular content of cyclic adenosine 3',5'-monophosphate decreased significantly.", "contents": "Transient repression of beta-galactosidase synthesis by glucose-6-phosphate in a mutant of Escherichia coli lacking enzyme II specific for glucose in the phosphoenolpyruvate-sugar phosphotransferase system. The effects of glucose and glucose-6-phosphate in initiating the repression of beta-galactosidase synthesis were studied using a mutant of Escherichia coli K12 which lacks glucose-specific enzyme II of the phosphoenolpyruvate-sugar phosphotransferase system. It was found that glucose-6-phosphate causes transient repression of beta-galactosidase synthesis but glucose does not cause transient repression in this mutant. Evidence was obtained that both the presence of an active transport system for glucose-6-phosphate in the cells and glucose-6-phosphate in the medium are necessary for the initiation of transient repression. No metabolism of glucose-6-phosphate is required. Upon depletion of glucose-6-phosphate in the medium the transient repression was reversed. After the reversal the rate of enzyme synthesis was high in the cells which had been exposed to a high concentration of glucose-6-phosphate. It was concluded that the translocation of glucose-6-phosphate across the membranes is the primary event which affects both the initiation of and the recovery from the transient repression. During the transient repression the cellular content of cyclic adenosine 3',5'-monophosphate decreased significantly."}
{"id": "PMID:207685", "title": "Ca2+/protein modulator-dependent and -independent cyclic GMP phosphodiesterase from hog heart.", "content": "Ca2+/protein modulator-dependent and -independent guanosine 3':5'-monophosphate (cGMP) phosphodiesterases were separated from hog heart. The protein modulator-free Ca2+/protein modulator-dependent enzyme was partially purified by repeated DEAE-cellulose column chromatography and heat treatment. The final preparation of this enzyme showed no significant basal activity under the standard assay conditions. Lineweaver-Burk plots of the Ca2+/protein modulator-dependent enzyme activity indicated the presence of only a single kinetic form of the enzyme with Km=2.0 X 10(-6) M for for cGMP, whereas the plots for the independent enzyme were anomalous, showing both high and low K m values for cGMP. The Ca2+/protein modulator-dependent enzyme proved relatively stable at 48 degrees C for 1 h, but the independent form lost its activity under the same conditions. Furthermore, 50% inhibition of the dependent enzyme activity, but only 10% inhibition of the independent enzyme activity, was observed with 0.1 mM adenosine 3':5'-monophosphate (cAMP) when 1 muM cGMP was employed as a substrate.", "contents": "Ca2+/protein modulator-dependent and -independent cyclic GMP phosphodiesterase from hog heart. Ca2+/protein modulator-dependent and -independent guanosine 3':5'-monophosphate (cGMP) phosphodiesterases were separated from hog heart. The protein modulator-free Ca2+/protein modulator-dependent enzyme was partially purified by repeated DEAE-cellulose column chromatography and heat treatment. The final preparation of this enzyme showed no significant basal activity under the standard assay conditions. Lineweaver-Burk plots of the Ca2+/protein modulator-dependent enzyme activity indicated the presence of only a single kinetic form of the enzyme with Km=2.0 X 10(-6) M for for cGMP, whereas the plots for the independent enzyme were anomalous, showing both high and low K m values for cGMP. The Ca2+/protein modulator-dependent enzyme proved relatively stable at 48 degrees C for 1 h, but the independent form lost its activity under the same conditions. Furthermore, 50% inhibition of the dependent enzyme activity, but only 10% inhibition of the independent enzyme activity, was observed with 0.1 mM adenosine 3':5'-monophosphate (cAMP) when 1 muM cGMP was employed as a substrate."}
{"id": "PMID:207686", "title": "Enzyme immunoassay of viomycin. New cross-linking reagent for enzyme labelling and a preparation method for antiserum to viomycin.", "content": "A new cross-linking reagent of the hetero-bisfunctional type, a N-(maleimidobenzoyloxy)-succinimide (MBS) was prepared and used for enzyme labelling of viomycin under mild aqueous conditions by a two-step process. In the first step a maleimide residue was selectively introduced onto the N1-amino group of viomycin with a limited amount of MBS. The second step consisted of thioether formation between the maleimide residue and free thiol groups of beta-D-galactosidase. An antiserum to viomycin was raised in rabbit by immunization with a viomycin-BSA conjugate. The conjugate was prepared by protecting N6-amino group of viomycin with an acetyl group and succinylating the N1-amino group, activating the carboxyl group by a mixed anhydride method and coupling it with the amino groups of bovine serum albumin (BSA). The specificity of the antiserum was proved by an enzyme immunoassay based on the competition between viomycin and its enzyme conjugate toward diluted solutions of the antiserum. By use of the viomycin-enzyme conjugate and the antiserum to viomycin, enzyme immunoassay of viomycin was successfully performed by the competitive binding procedure with the double-antibody method, and 0.1 to 4 ng of the antibiotic could be detected.", "contents": "Enzyme immunoassay of viomycin. New cross-linking reagent for enzyme labelling and a preparation method for antiserum to viomycin. A new cross-linking reagent of the hetero-bisfunctional type, a N-(maleimidobenzoyloxy)-succinimide (MBS) was prepared and used for enzyme labelling of viomycin under mild aqueous conditions by a two-step process. In the first step a maleimide residue was selectively introduced onto the N1-amino group of viomycin with a limited amount of MBS. The second step consisted of thioether formation between the maleimide residue and free thiol groups of beta-D-galactosidase. An antiserum to viomycin was raised in rabbit by immunization with a viomycin-BSA conjugate. The conjugate was prepared by protecting N6-amino group of viomycin with an acetyl group and succinylating the N1-amino group, activating the carboxyl group by a mixed anhydride method and coupling it with the amino groups of bovine serum albumin (BSA). The specificity of the antiserum was proved by an enzyme immunoassay based on the competition between viomycin and its enzyme conjugate toward diluted solutions of the antiserum. By use of the viomycin-enzyme conjugate and the antiserum to viomycin, enzyme immunoassay of viomycin was successfully performed by the competitive binding procedure with the double-antibody method, and 0.1 to 4 ng of the antibiotic could be detected."}
{"id": "PMID:207687", "title": "Comparative study of glycolipid compositions of plasma membranes among two types of rat ascites hepatoma and normal rat liver.", "content": "Glycolipid composition of purified plasma membranes from rat ascites hepatomas, two island-forming cell-lines and two cell-lines of the free-type, and normal rat liver were compared. Ceramide monohexoside (CMH), ceramide dihexoside (CDH), and hematoside (GM3) were found in normal rat liver cell membranes. The island-type hepatomas contained ceramide trihexoside (CTh) and globoside besides CMH, CDH, and GM3. The free-type of hepatomas were characterized by the presence of asialo-type gangliosides but not GM3. The free-type of hepatomas were characterized by the presence of asialo-type gangliosides but not GM3. Blood group H active fucolipid was a major glycolipid in the free-type of ascites hepatoma cell (AH 7974 F). The increase of glycolipid content in cell membranes seemed to be accompanied with a decrease of cell adhesiveness.", "contents": "Comparative study of glycolipid compositions of plasma membranes among two types of rat ascites hepatoma and normal rat liver. Glycolipid composition of purified plasma membranes from rat ascites hepatomas, two island-forming cell-lines and two cell-lines of the free-type, and normal rat liver were compared. Ceramide monohexoside (CMH), ceramide dihexoside (CDH), and hematoside (GM3) were found in normal rat liver cell membranes. The island-type hepatomas contained ceramide trihexoside (CTh) and globoside besides CMH, CDH, and GM3. The free-type of hepatomas were characterized by the presence of asialo-type gangliosides but not GM3. The free-type of hepatomas were characterized by the presence of asialo-type gangliosides but not GM3. Blood group H active fucolipid was a major glycolipid in the free-type of ascites hepatoma cell (AH 7974 F). The increase of glycolipid content in cell membranes seemed to be accompanied with a decrease of cell adhesiveness."}
{"id": "PMID:207688", "title": "In vivo glucose-, glucagon-, and cAMP-induced changes in liver glycogen synthase phosphatase activity.", "content": "In normal fed rats, glycogen synthase D phosphatase activity in a glycogen pellet preparation was only partially inhibited (approximately 50%) by high concentrations of EDTA. However, the proportion of phosphatase activity inhibited by EDTA was markedly and rapidly (15 s) increased following glucagon or cAMP administration. Epinephrine administration did not alter the proportion of activity inhibited by EDTA. Glucose administration rapidly (2 min) reduced the proportion of synthase phosphatase activity inhibitable by EDTA. That is, the effect of glucose was just the opposite of that produced by glucagon or cAMP. Insulin administration had no effect on phosphatase activity. Synthase phosphatase activity assayed in the absence of EDTA was similar in all groups except for a moderate increase after glucose administration. Addition of Mg2+ completely reversed EDTA inhibition. Phosphorylase phosphatase activity in each group was not modified by addition of EDTA, although the percentage of phosphorylase in the alpha form was higher in glucagon-treated and lower in the glucose-treated animals as expected. These data suggest the presence of rapidly interconvertible forms of either synthase phosphatase or its substrate synthase D, detectable as a change in EDTA inhibitability and subject to glucose and glucagon control.", "contents": "In vivo glucose-, glucagon-, and cAMP-induced changes in liver glycogen synthase phosphatase activity. In normal fed rats, glycogen synthase D phosphatase activity in a glycogen pellet preparation was only partially inhibited (approximately 50%) by high concentrations of EDTA. However, the proportion of phosphatase activity inhibited by EDTA was markedly and rapidly (15 s) increased following glucagon or cAMP administration. Epinephrine administration did not alter the proportion of activity inhibited by EDTA. Glucose administration rapidly (2 min) reduced the proportion of synthase phosphatase activity inhibitable by EDTA. That is, the effect of glucose was just the opposite of that produced by glucagon or cAMP. Insulin administration had no effect on phosphatase activity. Synthase phosphatase activity assayed in the absence of EDTA was similar in all groups except for a moderate increase after glucose administration. Addition of Mg2+ completely reversed EDTA inhibition. Phosphorylase phosphatase activity in each group was not modified by addition of EDTA, although the percentage of phosphorylase in the alpha form was higher in glucagon-treated and lower in the glucose-treated animals as expected. These data suggest the presence of rapidly interconvertible forms of either synthase phosphatase or its substrate synthase D, detectable as a change in EDTA inhibitability and subject to glucose and glucagon control."}
{"id": "PMID:207689", "title": "The natural flavorprotein electron acceptor of trimethylamine dehydrogenase.", "content": "The isolation and partial characterization of a flavoprotein which functions as the electron acceptor of trimethylamine dehydrogenase (EC 1.5.99.7) from a methylotrophic bacterium is described. It has a molecular weight of 77,000 and is composed of two dissimilar subunits. All preparations examined contained only 1 mol of FAD/mol of the flavoprotein. Trimethylamine dehydrogenase, in the presence of trimethylamine or dithionite, reduced the flavoprotein to a stable anionic semiquinone form. No evidence for the participation of the fully reduced flavoprotein in catalysis could be obtained.", "contents": "The natural flavorprotein electron acceptor of trimethylamine dehydrogenase. The isolation and partial characterization of a flavoprotein which functions as the electron acceptor of trimethylamine dehydrogenase (EC 1.5.99.7) from a methylotrophic bacterium is described. It has a molecular weight of 77,000 and is composed of two dissimilar subunits. All preparations examined contained only 1 mol of FAD/mol of the flavoprotein. Trimethylamine dehydrogenase, in the presence of trimethylamine or dithionite, reduced the flavoprotein to a stable anionic semiquinone form. No evidence for the participation of the fully reduced flavoprotein in catalysis could be obtained."}
{"id": "PMID:207693", "title": "Steroid modulation of human serum albumin binding properties. A spin label study.", "content": "The binding isotherm and unique electron spin resonance spectral characteristics of a monoanionic spin label (1-gamma-aminobutyrate-5-N-(1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidinyl)-2,4-dinitrobenzene) and a dianionic spin label (1-glutamate-5-N-(1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidinyl)-2,4-dinitrobenzene) are used to prove the steroid modulation of serum albumin binding properties. Effects of a selected number of steroids (progesterone, testosterone, estradiol, aldosterone, estriol, corticosterone, deoxycorticosterone, hydrocortisone, and cortisone) on the binding isotherm of the monoanionic spin label binding to serum albumin have been determined. At the steroid/albumin ratio of 0.5 to 1, progesterone, testosterone, and estradiol enhance binding of the spin label at all concentrations studied. However, the remaining steroids exert an inhibitory effect at low spin label/albumin ratios and an enhancement effect at high spin label/albumin ratios. Progesterone and cortisone effects on the resonance spectra of the spin label bound to serum albumin confirm the enhancement and displacement properties of these ligands. Thus, like fatty acids, steroids may bind to either the primary or secondary bilirubin binding sites and also allosterically perturb the binding properties of serum albumin. The in vivo importance of the steroid-albumin interaction is discussed.", "contents": "Steroid modulation of human serum albumin binding properties. A spin label study. The binding isotherm and unique electron spin resonance spectral characteristics of a monoanionic spin label (1-gamma-aminobutyrate-5-N-(1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidinyl)-2,4-dinitrobenzene) and a dianionic spin label (1-glutamate-5-N-(1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidinyl)-2,4-dinitrobenzene) are used to prove the steroid modulation of serum albumin binding properties. Effects of a selected number of steroids (progesterone, testosterone, estradiol, aldosterone, estriol, corticosterone, deoxycorticosterone, hydrocortisone, and cortisone) on the binding isotherm of the monoanionic spin label binding to serum albumin have been determined. At the steroid/albumin ratio of 0.5 to 1, progesterone, testosterone, and estradiol enhance binding of the spin label at all concentrations studied. However, the remaining steroids exert an inhibitory effect at low spin label/albumin ratios and an enhancement effect at high spin label/albumin ratios. Progesterone and cortisone effects on the resonance spectra of the spin label bound to serum albumin confirm the enhancement and displacement properties of these ligands. Thus, like fatty acids, steroids may bind to either the primary or secondary bilirubin binding sites and also allosterically perturb the binding properties of serum albumin. The in vivo importance of the steroid-albumin interaction is discussed."}
{"id": "PMID:207696", "title": "Coenzyme A and carnitine distribution in normal and ischemic hearts.", "content": "The distribution of coenzyme A and carnitine between the mitochondrial and cytosolic compartments was determined in rat heart ventricular muscle. The CoA and carnitine levels of homogenate, mitochondrial, and postmitochondrial fractions were determined in nonperfused hearts and in hearts that were perfused under control and ischemic conditions. Using the mitochondrial marker enzymes, citrate synthase and cytochrome c oxidase, the cellular content of mitochondrial protein was determined to be 53 +/- 1.0 (nonperfused), 53.5 +/- 1.5 (control), and 58.1 +/- 2.2 (ischemic) mg/g of wet heart muscle. These values were used to calculate the contribution of the CoA and carnitine located in the mitochondrial compartment to the total cellular levels of CoA and carnitine. Under both control and ischemic conditions, approximately 95% of the cellular CoA was mitochondrial. The percentage of the total cellular carnitine associated with the mitochondria increased from 8 to 9% in nonperfused and control hearts to 25% during ischemia, indicating that a net transfer of carnitine occurred from the cytosol to the mitochondrial matrix.", "contents": "Coenzyme A and carnitine distribution in normal and ischemic hearts. The distribution of coenzyme A and carnitine between the mitochondrial and cytosolic compartments was determined in rat heart ventricular muscle. The CoA and carnitine levels of homogenate, mitochondrial, and postmitochondrial fractions were determined in nonperfused hearts and in hearts that were perfused under control and ischemic conditions. Using the mitochondrial marker enzymes, citrate synthase and cytochrome c oxidase, the cellular content of mitochondrial protein was determined to be 53 +/- 1.0 (nonperfused), 53.5 +/- 1.5 (control), and 58.1 +/- 2.2 (ischemic) mg/g of wet heart muscle. These values were used to calculate the contribution of the CoA and carnitine located in the mitochondrial compartment to the total cellular levels of CoA and carnitine. Under both control and ischemic conditions, approximately 95% of the cellular CoA was mitochondrial. The percentage of the total cellular carnitine associated with the mitochondria increased from 8 to 9% in nonperfused and control hearts to 25% during ischemia, indicating that a net transfer of carnitine occurred from the cytosol to the mitochondrial matrix."}
{"id": "PMID:207698", "title": "Identification of cytochrome c oxidase subunits in nuclear yeast mutants lacking the functional enzyme.", "content": "Yeast mutants specifically lacking cytochrome c oxidase activity were screened for cytochrome c oxidase subunits by one- and two-dimensional electrophoresis, electrophoresis in exponential gradient gels, and immunoprecipitation with antisera against one or more of the cytoplasmically made subunits of the enzyme. Two cytochrome c oxidase-less nuclear mutants previously described from this laboratory each lack one or more mitochondrially synthesized cytochrome c oxidase subunits while possessing all four cytoplasmically synthesized subunits of that enzyme. The subunits remaining in these mutants were not assembled with each other; the cytoplasmically made subunits IV and VI could be released from the mitochondria by sonic oscillation, in contrast to the situation in wild type cells. No electrophoretically detectable alterations were found in any of the cytochrome c oxidase subunits present in the mutants. Nuclear mutations may thus cause both a loss as well as a defective assembly of mitochondrially made cytochrome c oxidase subunits.", "contents": "Identification of cytochrome c oxidase subunits in nuclear yeast mutants lacking the functional enzyme. Yeast mutants specifically lacking cytochrome c oxidase activity were screened for cytochrome c oxidase subunits by one- and two-dimensional electrophoresis, electrophoresis in exponential gradient gels, and immunoprecipitation with antisera against one or more of the cytoplasmically made subunits of the enzyme. Two cytochrome c oxidase-less nuclear mutants previously described from this laboratory each lack one or more mitochondrially synthesized cytochrome c oxidase subunits while possessing all four cytoplasmically synthesized subunits of that enzyme. The subunits remaining in these mutants were not assembled with each other; the cytoplasmically made subunits IV and VI could be released from the mitochondria by sonic oscillation, in contrast to the situation in wild type cells. No electrophoretically detectable alterations were found in any of the cytochrome c oxidase subunits present in the mutants. Nuclear mutations may thus cause both a loss as well as a defective assembly of mitochondrially made cytochrome c oxidase subunits."}
{"id": "PMID:207699", "title": "Identification of enzymically inactive apocytochrome c peroxidase in anaerobically grown Saccharomyces cerevisiae.", "content": "Anaerobically grown yeast cells lack cytochrome c peroxidase activity but rapidly acquire it upon aeration. In order to study the oxygen-induced formation of this hemoprotein, extracts of anaerobic and aerobic yeast cells were resolved by one- and two-dimensional acrylamide gel electrophoresis and the separated polypeptides were then checked for comigration with radiolabeled purified cytochrome c peroxidase from aerobic cells or for reaction with cytochrome c peroxidase antiserum. Both types of extracts contained roughly equal amounts of a polypeptide which was indistinguishable from apocytochrome c peroxidase with respect to antigenicity, isoelectric point, and apparent molecular weight in three different gel systems. In confirmation of an earlier report by Sels. A.A., and Cocriamont, C. (1968) (Biochem. Biophus. Res. Commun. 32, 192-198) the oxygen-induced formation of cytochrome c peroxidase was insensitive to inhibitors of protein synthesis and could be mimicked by the addition of heme to extracts of anaerobic cells. We conclude that the oxygen-induced formation of yeast cytochrome c peroxidase involves the addition of heme to the apoenzyme which is already present in the anaerobically grown cells.", "contents": "Identification of enzymically inactive apocytochrome c peroxidase in anaerobically grown Saccharomyces cerevisiae. Anaerobically grown yeast cells lack cytochrome c peroxidase activity but rapidly acquire it upon aeration. In order to study the oxygen-induced formation of this hemoprotein, extracts of anaerobic and aerobic yeast cells were resolved by one- and two-dimensional acrylamide gel electrophoresis and the separated polypeptides were then checked for comigration with radiolabeled purified cytochrome c peroxidase from aerobic cells or for reaction with cytochrome c peroxidase antiserum. Both types of extracts contained roughly equal amounts of a polypeptide which was indistinguishable from apocytochrome c peroxidase with respect to antigenicity, isoelectric point, and apparent molecular weight in three different gel systems. In confirmation of an earlier report by Sels. A.A., and Cocriamont, C. (1968) (Biochem. Biophus. Res. Commun. 32, 192-198) the oxygen-induced formation of cytochrome c peroxidase was insensitive to inhibitors of protein synthesis and could be mimicked by the addition of heme to extracts of anaerobic cells. We conclude that the oxygen-induced formation of yeast cytochrome c peroxidase involves the addition of heme to the apoenzyme which is already present in the anaerobically grown cells."}
{"id": "PMID:207704", "title": "Purification of rat liver nuclear protein kinase NI.", "content": "Rat liver nuclear protein kinase NI, which appears in the flowthrough of DEAE-Sephadex columns, has been purified approximately 15,000-fold from soluble nuclear protein with yields of up to 10%. The method of purification involved chromatography of the DEAE-flowthrough protein successively on phosvitin-Sepharose and casein-Sepharose followed by rechromatography on phosvitin-Sepharose. The purified enzyme has an s20,w and molecular weight of 3.7 and 47,000, respectively, as determined by sucrose density gradient centrifugation in 0.4 M NaCl. A similar molecular weight of 42,000 was determined by gel filtration using Sephadex G-100. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme revealed a single polypeptide with a molecular weight of 25,000. Protein kinase NI therefore consists of a dimer of two identical subunits. Protein kinase NI exhibits maximal activity on casein substrate and is not stimulated by 10(-5) to 10(-4) M cAMP or cGMP when either casein or histone H2b is used as a substrate.", "contents": "Purification of rat liver nuclear protein kinase NI. Rat liver nuclear protein kinase NI, which appears in the flowthrough of DEAE-Sephadex columns, has been purified approximately 15,000-fold from soluble nuclear protein with yields of up to 10%. The method of purification involved chromatography of the DEAE-flowthrough protein successively on phosvitin-Sepharose and casein-Sepharose followed by rechromatography on phosvitin-Sepharose. The purified enzyme has an s20,w and molecular weight of 3.7 and 47,000, respectively, as determined by sucrose density gradient centrifugation in 0.4 M NaCl. A similar molecular weight of 42,000 was determined by gel filtration using Sephadex G-100. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme revealed a single polypeptide with a molecular weight of 25,000. Protein kinase NI therefore consists of a dimer of two identical subunits. Protein kinase NI exhibits maximal activity on casein substrate and is not stimulated by 10(-5) to 10(-4) M cAMP or cGMP when either casein or histone H2b is used as a substrate."}
{"id": "PMID:207707", "title": "Permeation of the erythrocyte stroma by superoxide radical.", "content": "Superoxide anion, generated by xanthine oxidase within vesicles formed from washed erythrocyte ghosts, crosses the vesicle membrane to reduce cytochrome c in the medium (Lynch, R. E., and Fridovich, I. (1978) J. Biol. Chem, 253, 1838-1845). To determine whether O2- could travel through the membrane in the \"channel\" for the exchange of stable anions, the effects of two specific inhibitors of anion exchange, 4-acetamido-4'-isothiocyano-2,2' disulfonic acid stilbene (SITS) and 4,4'-diisothiocyano-2,2' disulfonic acid stilbene (DIDS), on the escape of O2- from vesicles were studied. The reduction of external cytochrome c, caused by O2- produced by the enzymic turnover of internal xanthine oxidase, was 85 to 90% inhibited by SITS and DIDS. If SITS impeded the egress of O2- from vesicles, it should enhance the internal effects of O2- and antagonize the inhibition of these effects by external superoxide dismutase. External superoxide dismutase inhibited the lysis of vesicles containing xanthine oxidase. SITS (60 micron) partially reversed this inhibition. It appears that O2- can cross the membrane of the erythrocyte in the anion channel.", "contents": "Permeation of the erythrocyte stroma by superoxide radical. Superoxide anion, generated by xanthine oxidase within vesicles formed from washed erythrocyte ghosts, crosses the vesicle membrane to reduce cytochrome c in the medium (Lynch, R. E., and Fridovich, I. (1978) J. Biol. Chem, 253, 1838-1845). To determine whether O2- could travel through the membrane in the \"channel\" for the exchange of stable anions, the effects of two specific inhibitors of anion exchange, 4-acetamido-4'-isothiocyano-2,2' disulfonic acid stilbene (SITS) and 4,4'-diisothiocyano-2,2' disulfonic acid stilbene (DIDS), on the escape of O2- from vesicles were studied. The reduction of external cytochrome c, caused by O2- produced by the enzymic turnover of internal xanthine oxidase, was 85 to 90% inhibited by SITS and DIDS. If SITS impeded the egress of O2- from vesicles, it should enhance the internal effects of O2- and antagonize the inhibition of these effects by external superoxide dismutase. External superoxide dismutase inhibited the lysis of vesicles containing xanthine oxidase. SITS (60 micron) partially reversed this inhibition. It appears that O2- can cross the membrane of the erythrocyte in the anion channel."}
{"id": "PMID:207708", "title": "Cyclic AMP-dependent phosphorylation of filamin in mammalian smooth muscle.", "content": "Filamin is a high molecular weight actin-binding protein found in large quantities in smooth muscle and other non-muscle cells. We have studied the phosphorylation of filamin in a mammalian smooth muscle, the guinea pig vas deferens. Intact vas deferens incorporated [32P]orthophosphate into filamin. Incubation of particulate fractions of vas deferens with [gamma-32P]ATP resulted in 32P-labeling of filamin. Cyclic AMP stimulated this phosphorylation, whereas cyclic GMP and Ca2+ had no effect. Purified vas deferens filamin can be phosphorylated by purified cyclic AMP-dependent protein kinase. We have compared cyclic AMP and cyclic GMP effects on phosphorylation in smooth muscle. Cyclic GMP stimulated phosphorylation of two particulate proteins, G-I (Mr = 130,000) a protein previously described by Casnellie, J. E., and Greengard, P. (1974) Proc. Natl. Acad, Sci. U.S.A. 71, 1891-1895 and G-III (Mr = 240,000). Both proteins and the kinase responsible for their phosphorylation appear to be membrane-bound. Phosphorylation of both proteins is stimulated by cyclic GMP (Ka = 3 x 10(-8) M), cyclic AMP (Ka = 3 x 10(-7) M), and to a lesser degree by Ca2+. In contrast, filamin phosphorylation is due to a soluble kinase stimulated only by cyclic AMP (Ka = 3 x 10(-7) M) and not by cyclic GMP or Ca2+.", "contents": "Cyclic AMP-dependent phosphorylation of filamin in mammalian smooth muscle. Filamin is a high molecular weight actin-binding protein found in large quantities in smooth muscle and other non-muscle cells. We have studied the phosphorylation of filamin in a mammalian smooth muscle, the guinea pig vas deferens. Intact vas deferens incorporated [32P]orthophosphate into filamin. Incubation of particulate fractions of vas deferens with [gamma-32P]ATP resulted in 32P-labeling of filamin. Cyclic AMP stimulated this phosphorylation, whereas cyclic GMP and Ca2+ had no effect. Purified vas deferens filamin can be phosphorylated by purified cyclic AMP-dependent protein kinase. We have compared cyclic AMP and cyclic GMP effects on phosphorylation in smooth muscle. Cyclic GMP stimulated phosphorylation of two particulate proteins, G-I (Mr = 130,000) a protein previously described by Casnellie, J. E., and Greengard, P. (1974) Proc. Natl. Acad, Sci. U.S.A. 71, 1891-1895 and G-III (Mr = 240,000). Both proteins and the kinase responsible for their phosphorylation appear to be membrane-bound. Phosphorylation of both proteins is stimulated by cyclic GMP (Ka = 3 x 10(-8) M), cyclic AMP (Ka = 3 x 10(-7) M), and to a lesser degree by Ca2+. In contrast, filamin phosphorylation is due to a soluble kinase stimulated only by cyclic AMP (Ka = 3 x 10(-7) M) and not by cyclic GMP or Ca2+."}
{"id": "PMID:207710", "title": "Skeletal diseases associated with angiomatosis.", "content": "Basically, there are two conditions in which angiomatosis is associated with underlying skeletal disease. The first is Maffucci's syndrome in which angiomatosis is associated with multiple enchondromatosis. Two patients with this disease are presented and its clinical and radiologic features are reviewed. The second is \"congenital angiectatic hypertrophy\" in which angiomatosis is associated with localized hypertrophy of underlying bones, soft tissues and occasionally internal vercera. Four patients with this condition are presented, illustrating the subtypes of closely related diseases within a broad spectrum.", "contents": "Skeletal diseases associated with angiomatosis. Basically, there are two conditions in which angiomatosis is associated with underlying skeletal disease. The first is Maffucci's syndrome in which angiomatosis is associated with multiple enchondromatosis. Two patients with this disease are presented and its clinical and radiologic features are reviewed. The second is \"congenital angiectatic hypertrophy\" in which angiomatosis is associated with localized hypertrophy of underlying bones, soft tissues and occasionally internal vercera. Four patients with this condition are presented, illustrating the subtypes of closely related diseases within a broad spectrum."}
{"id": "PMID:207711", "title": "Quantitative correlation between simian virus 40 T-antigen synthesis and late viral gene expression in permissive and nonpermissive cells.", "content": "The time-course of intranuclear Simian virus 40 (SV40) tumor (T) antigen synthesis and accumulation in permissive CV1 monkey cells and nonpermissive 3T3 mouse cells has been studied by immunofluorescence and cytofluorometry. CV1 cells accumulate T antigen continuously over a period of 48 h after infection, whereas in 3T3 cells the T-antigen content remains about constant and at a comparatively low level. Only those CV1 cells which have attained a threshold concentration of intranuclear T antigen synthesize viral capsid proteins (V antigen). In nonpermissive 3T3 cells, the T-antigen threshold value for the onset of V-antigen synthesis is higher than in CV1 cells and is never reached by infected cells. However, 3T3 cells microinjected with sufficient amounts of SV40 DNA easily surpass this value and behave permissively.", "contents": "Quantitative correlation between simian virus 40 T-antigen synthesis and late viral gene expression in permissive and nonpermissive cells. The time-course of intranuclear Simian virus 40 (SV40) tumor (T) antigen synthesis and accumulation in permissive CV1 monkey cells and nonpermissive 3T3 mouse cells has been studied by immunofluorescence and cytofluorometry. CV1 cells accumulate T antigen continuously over a period of 48 h after infection, whereas in 3T3 cells the T-antigen content remains about constant and at a comparatively low level. Only those CV1 cells which have attained a threshold concentration of intranuclear T antigen synthesize viral capsid proteins (V antigen). In nonpermissive 3T3 cells, the T-antigen threshold value for the onset of V-antigen synthesis is higher than in CV1 cells and is never reached by infected cells. However, 3T3 cells microinjected with sufficient amounts of SV40 DNA easily surpass this value and behave permissively."}
{"id": "PMID:207713", "title": "[Gas chromatographic estimation of acidic urinary metabolites after separation on prepacked silica gel columns (author's transl)].", "content": "The acidic ethylacetate extracts of 24-h urine specimens are evaporated and redissolved in chloroform--methanol--acetic acid. The resulting solution is transferred to a prepacked silica gel column. Elution takes 160 min using a specially designed chloroform--methanol--acetic acid gradient. The eluate  is divided into fractions (16 min each) which are evaporated to dryness. The residues are silvlated and determined quantitatively by gas chromatography. The capacity of the silica gel column allows analysis of 30% of a 24-h urine specimen. In consequence, metabolites can be quantitated at concentrations less than 1 mg per 24 h. The method is suitable to obtain more detailed metabolic profiles of the carboxylic acids in urine.", "contents": "[Gas chromatographic estimation of acidic urinary metabolites after separation on prepacked silica gel columns (author's transl)]. The acidic ethylacetate extracts of 24-h urine specimens are evaporated and redissolved in chloroform--methanol--acetic acid. The resulting solution is transferred to a prepacked silica gel column. Elution takes 160 min using a specially designed chloroform--methanol--acetic acid gradient. The eluate  is divided into fractions (16 min each) which are evaporated to dryness. The residues are silvlated and determined quantitatively by gas chromatography. The capacity of the silica gel column allows analysis of 30% of a 24-h urine specimen. In consequence, metabolites can be quantitated at concentrations less than 1 mg per 24 h. The method is suitable to obtain more detailed metabolic profiles of the carboxylic acids in urine."}
{"id": "PMID:207716", "title": "High-performance liquid chromatography determination of potential content of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) in resins, oils, dry concentrates and multivitamin formulations.", "content": "The determination of potential vitamin D concentrations in raw materials and in multivitamin formulations by high-performance liquid chromatography is reported. Simple experimental conditions allow the rapid separation of the vitamins from their respective pro- and pre-vitamins, from their irradiation side-products and from some of their overirradiation products. Vitamin extraction is performed directly from dry concentrates, tablets and capsules, without saponification; all procedures are carried out at room temperature so as to preserve the ratio of vitamin D and pre-vitamin D present in the prepatation. The relative standard deviation is less than 1.5%.", "contents": "High-performance liquid chromatography determination of potential content of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) in resins, oils, dry concentrates and multivitamin formulations. The determination of potential vitamin D concentrations in raw materials and in multivitamin formulations by high-performance liquid chromatography is reported. Simple experimental conditions allow the rapid separation of the vitamins from their respective pro- and pre-vitamins, from their irradiation side-products and from some of their overirradiation products. Vitamin extraction is performed directly from dry concentrates, tablets and capsules, without saponification; all procedures are carried out at room temperature so as to preserve the ratio of vitamin D and pre-vitamin D present in the prepatation. The relative standard deviation is less than 1.5%."}
{"id": "PMID:207717", "title": "Human rotavirus and its antibody: their coexistence in feces of infants.", "content": "Rotavirus and its antibody were detected by paper disk solid-phase radioimmunoassay or electron microscopy in feces of infants and young children with acute diarrhea. The fecal specimens in which rotavirus was detectable often contained a high titer of antibodies, which were shown by radioimmunoassay to belong mainly to the immunoglobulin G class. Rotavirus was rarely detected in the specimens containing immunoglobulin A antibodies. By dissociation tests carried out by radioimmunoassay, it was shown that the rotavirus particles in some specimens had the same antibody-binding capacity as did cultured simian rotavirus (SA-11), but antibodies in feces usually had low avidity, probably resulting from enzymatic digestion.", "contents": "Human rotavirus and its antibody: their coexistence in feces of infants. Rotavirus and its antibody were detected by paper disk solid-phase radioimmunoassay or electron microscopy in feces of infants and young children with acute diarrhea. The fecal specimens in which rotavirus was detectable often contained a high titer of antibodies, which were shown by radioimmunoassay to belong mainly to the immunoglobulin G class. Rotavirus was rarely detected in the specimens containing immunoglobulin A antibodies. By dissociation tests carried out by radioimmunoassay, it was shown that the rotavirus particles in some specimens had the same antibody-binding capacity as did cultured simian rotavirus (SA-11), but antibodies in feces usually had low avidity, probably resulting from enzymatic digestion."}
{"id": "PMID:207718", "title": "Agar-gel immunodiffusion assay for pseudorabies virus antibody.", "content": "Soluble antigen prepared from pseudorabies virus-infected embryonic pig kidney cells was used to demonstrate the presence of pseudorabies virus antibodies in sera taken from naturally and experimentally infected swine. Antibody could be detected by agar-gel immunodiffusion as early as 14 days postexposure and was demonstrable at least 3 months after experimental infection (the longest period tested). The reliability of the agar-gel immunodiffusion test was comparable to that of the microtitration serum-virus neutralization test commonly used in diagnostic laboratories. One advantage of the agar-gel immunodiffusion test was that severely hemolyzed and cytotoxic serum samples could be tested with confidence. The test is simple, rapid, and inexpensive and could be easily adopted by diagnostic laboratories that receive requests for pseudorabies virus antibody determinations in swine sera.", "contents": "Agar-gel immunodiffusion assay for pseudorabies virus antibody. Soluble antigen prepared from pseudorabies virus-infected embryonic pig kidney cells was used to demonstrate the presence of pseudorabies virus antibodies in sera taken from naturally and experimentally infected swine. Antibody could be detected by agar-gel immunodiffusion as early as 14 days postexposure and was demonstrable at least 3 months after experimental infection (the longest period tested). The reliability of the agar-gel immunodiffusion test was comparable to that of the microtitration serum-virus neutralization test commonly used in diagnostic laboratories. One advantage of the agar-gel immunodiffusion test was that severely hemolyzed and cytotoxic serum samples could be tested with confidence. The test is simple, rapid, and inexpensive and could be easily adopted by diagnostic laboratories that receive requests for pseudorabies virus antibody determinations in swine sera."}
{"id": "PMID:207719", "title": "Use of isolated nuclei in the indirect fluorescent-antibody test for human cytomegalovirus infection: comparison with microneutralization, anticomplement, and conventional indirect fluorescent-antibody assays.", "content": "Use of an antigen consisting of purified isolated nuclei from a mixture of human cytomegalovirus-infected and uninfected fibroblasts in a 2:1 ratio is a simple and reliable method for eliminating nonspecific fluorescence associated with the presence of Fc-immunoglobulin G receptors in the cytoplasm of infected cells. The specificity obtained with this antigen on 100 normal human sera was 99, 100, and 98% when compared with microneutralization, anticomplement immunofluorescence, and conventional indirect fluorescent-antibody assays, respectively. Also, 95% of the antibody titers obtained with the nuclear antigen had a perfect correlation with or were within a fourfold-dilution difference of the antibody levels obtained by anticomplement immunofluorescence and the conventional indirect fluorescent-antibody test.", "contents": "Use of isolated nuclei in the indirect fluorescent-antibody test for human cytomegalovirus infection: comparison with microneutralization, anticomplement, and conventional indirect fluorescent-antibody assays. Use of an antigen consisting of purified isolated nuclei from a mixture of human cytomegalovirus-infected and uninfected fibroblasts in a 2:1 ratio is a simple and reliable method for eliminating nonspecific fluorescence associated with the presence of Fc-immunoglobulin G receptors in the cytoplasm of infected cells. The specificity obtained with this antigen on 100 normal human sera was 99, 100, and 98% when compared with microneutralization, anticomplement immunofluorescence, and conventional indirect fluorescent-antibody assays, respectively. Also, 95% of the antibody titers obtained with the nuclear antigen had a perfect correlation with or were within a fourfold-dilution difference of the antibody levels obtained by anticomplement immunofluorescence and the conventional indirect fluorescent-antibody test."}
{"id": "PMID:207720", "title": "Measurement of neutralizing antibody to equid herpesvirus 1 by single radial hemolysis.", "content": "Antibody to equid herpesvirus 1, which mediates single radial hemolysis, is that responsible for neutralization. Hemagglutination inhibition antibody is not necessarily involved in neutralization or hemolysis.", "contents": "Measurement of neutralizing antibody to equid herpesvirus 1 by single radial hemolysis. Antibody to equid herpesvirus 1, which mediates single radial hemolysis, is that responsible for neutralization. Hemagglutination inhibition antibody is not necessarily involved in neutralization or hemolysis."}
{"id": "PMID:207721", "title": "Immediate and time-dependent effects of glucose on insulin release from rat pancreatic tissue. Evidence for different mechanisms of action.", "content": "Glucose-induced insulin secretion is enhanced by a preceeding glucose stimulus. The characteristics of this action of glucose were investigated in perfused pancreas and collagenase-isolated islets of Langerhans. A 20- to 30-min pulse of 27.7 mM glucose enhanced both the first and second phase of insulin release in response to a second glucose stimulus by 76-201%. This enhancement was apparent as an augmented maximal insulin release response to glucose. The effect of priming with glucose was seen irrespective of whether the pancreatic tissue was obtained from fed or fasted rats. Separating the two pulses of hexose by a 60-min time interval of exposure to 3.3 mM glucose did not abolish the potentiation of the second pulse. Omission of Ca(++) as well as the inclusion of somatostatin or mannoheptulose during the first pulse abolished insulin secretion during this time period; however, only the inclusion of mannoheptulose deleted the potentiation of the second pulse. d-Glyceraldehyde, but not pyruvate, d-galactose, or 3-isobutyl-1-methylxanthine, could substitute for glucose in inducing potentiation. In islets labeled with [2-(3)H]adenine, the [(3)H]cyclic AMP response to glucose was increased by 35% when measured after 1 min, but was increased only marginally after 2-10 min of stimulation with a second pulse of glucose. The production of (3)H(2)O from glucose was not affected by glucose priming. It is concluded that (a) the induction of the glucose-induced, time-dependent potentiation described here is dependent on glucose metabolism but not on stimulation of cyclic AMP, calcium fluxes, or insulin release per se; (b) the mechanisms that mediate the pancreatic \"memory\" for glucose are unknown but do not seem to involve to a major extent an increased activity of the adenylate cyclase-cyclic AMP system of the beta-cell; (c) the evidence presented supports the hypothesis of a dual role of glucose for insulin release.", "contents": "Immediate and time-dependent effects of glucose on insulin release from rat pancreatic tissue. Evidence for different mechanisms of action. Glucose-induced insulin secretion is enhanced by a preceeding glucose stimulus. The characteristics of this action of glucose were investigated in perfused pancreas and collagenase-isolated islets of Langerhans. A 20- to 30-min pulse of 27.7 mM glucose enhanced both the first and second phase of insulin release in response to a second glucose stimulus by 76-201%. This enhancement was apparent as an augmented maximal insulin release response to glucose. The effect of priming with glucose was seen irrespective of whether the pancreatic tissue was obtained from fed or fasted rats. Separating the two pulses of hexose by a 60-min time interval of exposure to 3.3 mM glucose did not abolish the potentiation of the second pulse. Omission of Ca(++) as well as the inclusion of somatostatin or mannoheptulose during the first pulse abolished insulin secretion during this time period; however, only the inclusion of mannoheptulose deleted the potentiation of the second pulse. d-Glyceraldehyde, but not pyruvate, d-galactose, or 3-isobutyl-1-methylxanthine, could substitute for glucose in inducing potentiation. In islets labeled with [2-(3)H]adenine, the [(3)H]cyclic AMP response to glucose was increased by 35% when measured after 1 min, but was increased only marginally after 2-10 min of stimulation with a second pulse of glucose. The production of (3)H(2)O from glucose was not affected by glucose priming. It is concluded that (a) the induction of the glucose-induced, time-dependent potentiation described here is dependent on glucose metabolism but not on stimulation of cyclic AMP, calcium fluxes, or insulin release per se; (b) the mechanisms that mediate the pancreatic \"memory\" for glucose are unknown but do not seem to involve to a major extent an increased activity of the adenylate cyclase-cyclic AMP system of the beta-cell; (c) the evidence presented supports the hypothesis of a dual role of glucose for insulin release."}
{"id": "PMID:207722", "title": "Superoxide production by digitonin-stimulated guinea pig granulocytes. The effects of N-ethyl maleimide, divalent cations; and glycolytic and mitochondrial inhibitors on the activation of the superoxide generating system.", "content": "N-ethylmaleimide, divalent cations, ethylene glycol bis (beta aminoethyl ether) N,N,N',N',-tetraacetate, 2-deoxyglucose, cyanide, and dinitrophenol were examined for their effect on the ability of guinea pig granulocytes to generate superoxide (O(2) (-)) when stimulated by digitonin. N-ethylmaleimide (1 mM) inhibits only when added before complete activation of the O(2) (-) generating system, and at lower concentrations (0.05-0.2 mM) slows the activation process. Ca(++) is required for maximum O(2) (-) generation, and Mg(++) decreases the amount of Ca(++) required. Ethylene glycol bis (beta aminoethyl ether) N,N,N',N',-tetraacetate (10 mM) inhibits only if added before complete activation. Incubation of cells in 2-DOG causes a time- and concentration-dependent inhibition of O(2) (-) generation. It also increases the time required for activation of this system. Cyanide and dinitrophenol increase the rate of O(2) (-) production. However, when these compounds are added to cells whose O(2) (-) production is partially inhibited by incubation in 2-deoxyglucose, complete inhibition results. If cyanide or dinitrophenol is added after activation of 2-deoxyglucose-treated cells, no further inhibition occurs. On the basis of the above results, we conclude that the activation of the O(2) (-) generating system is N-ethylmaleimide sensitive, Ca(++) dependent, and energy requiring, but that the activity of the enzyme system in the cell is not.", "contents": "Superoxide production by digitonin-stimulated guinea pig granulocytes. The effects of N-ethyl maleimide, divalent cations; and glycolytic and mitochondrial inhibitors on the activation of the superoxide generating system. N-ethylmaleimide, divalent cations, ethylene glycol bis (beta aminoethyl ether) N,N,N',N',-tetraacetate, 2-deoxyglucose, cyanide, and dinitrophenol were examined for their effect on the ability of guinea pig granulocytes to generate superoxide (O(2) (-)) when stimulated by digitonin. N-ethylmaleimide (1 mM) inhibits only when added before complete activation of the O(2) (-) generating system, and at lower concentrations (0.05-0.2 mM) slows the activation process. Ca(++) is required for maximum O(2) (-) generation, and Mg(++) decreases the amount of Ca(++) required. Ethylene glycol bis (beta aminoethyl ether) N,N,N',N',-tetraacetate (10 mM) inhibits only if added before complete activation. Incubation of cells in 2-DOG causes a time- and concentration-dependent inhibition of O(2) (-) generation. It also increases the time required for activation of this system. Cyanide and dinitrophenol increase the rate of O(2) (-) production. However, when these compounds are added to cells whose O(2) (-) production is partially inhibited by incubation in 2-deoxyglucose, complete inhibition results. If cyanide or dinitrophenol is added after activation of 2-deoxyglucose-treated cells, no further inhibition occurs. On the basis of the above results, we conclude that the activation of the O(2) (-) generating system is N-ethylmaleimide sensitive, Ca(++) dependent, and energy requiring, but that the activity of the enzyme system in the cell is not."}
{"id": "PMID:207723", "title": "Thrombin generation and secretion of platelet Factor 4 during blood clotting.", "content": "We have studied the platelet release reaction and thrombin generation during the spontaneous clotting of whole blood in vitro. Both thrombin formation and secretion of platelet Factor 4 were detected at least 12 min before clotting (clotting time, 22--26 min). Initially, at low thrombin concentrations (2--5 ng/ml), there is a small increase in plasma platelet Factor 4 (less than 1% of the amount present in serum). This is followed by a gradual increase in both platelet Factor 4 and thrombin concentrations over a 12 to 20-min interval. Finally, 5 min 5 before clotting, there is a rapid increase in both thrombin generation and platelet secretion. Thus, we have shown that the release of platelet Factor 4 is a prolonged reactoin and the extent to which it occurs parallel thrombin generation. It is only when thrombin concentrations are high (45--90) ng/ml)--during the period of clot formation--that the major part of platelet Factor 4 secretion occurs. Release of platelet Factor 4, like fibrin formation, occurs in the last step of in vitro coagulation.", "contents": "Thrombin generation and secretion of platelet Factor 4 during blood clotting. We have studied the platelet release reaction and thrombin generation during the spontaneous clotting of whole blood in vitro. Both thrombin formation and secretion of platelet Factor 4 were detected at least 12 min before clotting (clotting time, 22--26 min). Initially, at low thrombin concentrations (2--5 ng/ml), there is a small increase in plasma platelet Factor 4 (less than 1% of the amount present in serum). This is followed by a gradual increase in both platelet Factor 4 and thrombin concentrations over a 12 to 20-min interval. Finally, 5 min 5 before clotting, there is a rapid increase in both thrombin generation and platelet secretion. Thus, we have shown that the release of platelet Factor 4 is a prolonged reactoin and the extent to which it occurs parallel thrombin generation. It is only when thrombin concentrations are high (45--90) ng/ml)--during the period of clot formation--that the major part of platelet Factor 4 secretion occurs. Release of platelet Factor 4, like fibrin formation, occurs in the last step of in vitro coagulation."}
{"id": "PMID:207724", "title": "Low density lipoprotein. A metabolic pathway for return of cholesterol to the splanchnic bed.", "content": "The mechanism(s) by which cholesterol returns to the splanchnic bed from peripheral tissues are not well understood. To study this phenomenon in fasting man, lipoproteins were isolated from plasma obtained from hepatic vein and aorta. Cholesterol content of each lipoprotein class was determined and arteriovenous (AV) differences could be calculated for each patient. The results in the first 24 patients indicated splanchnic secretion of very low density lipoprotein cholesterol (mean AV difference - 3 mg/100 ml, P < 0.01), but not significant AV difference for total cholesterol, high density lipoprotein cholesterol, or low density lipoprotein (LDL) B protein. In contrast, for LDL (d 1.006-1.063 g/ml), there was significant uptake of cholesterol across the AV bed +8 mg/100 ml, P < 0.0002). In a further 15 patients, similar samples were obtained and intermediate density lipoprotein isolated at d 1.006-1.019 g/ml and LDL at 1.019-1.063 g/ml. The AV difference previously noted could now be localized to the 1.019-1.063 cholesterol ester moiety (+8 mg/100 ml, P < 0.0005). In the final 14 patients, the LDL cholesterol AV difference was again confirmed and shown to be unrelated to heparin. As well, there was secretion of triglyceride in the hepatic vein LDL. These quantitative data obtained in man raise the possibility that LDL rather than high density lipoprotein transports cholesterol ester to the splanchnic bed.", "contents": "Low density lipoprotein. A metabolic pathway for return of cholesterol to the splanchnic bed. The mechanism(s) by which cholesterol returns to the splanchnic bed from peripheral tissues are not well understood. To study this phenomenon in fasting man, lipoproteins were isolated from plasma obtained from hepatic vein and aorta. Cholesterol content of each lipoprotein class was determined and arteriovenous (AV) differences could be calculated for each patient. The results in the first 24 patients indicated splanchnic secretion of very low density lipoprotein cholesterol (mean AV difference - 3 mg/100 ml, P < 0.01), but not significant AV difference for total cholesterol, high density lipoprotein cholesterol, or low density lipoprotein (LDL) B protein. In contrast, for LDL (d 1.006-1.063 g/ml), there was significant uptake of cholesterol across the AV bed +8 mg/100 ml, P < 0.0002). In a further 15 patients, similar samples were obtained and intermediate density lipoprotein isolated at d 1.006-1.019 g/ml and LDL at 1.019-1.063 g/ml. The AV difference previously noted could now be localized to the 1.019-1.063 cholesterol ester moiety (+8 mg/100 ml, P < 0.0005). In the final 14 patients, the LDL cholesterol AV difference was again confirmed and shown to be unrelated to heparin. As well, there was secretion of triglyceride in the hepatic vein LDL. These quantitative data obtained in man raise the possibility that LDL rather than high density lipoprotein transports cholesterol ester to the splanchnic bed."}
{"id": "PMID:207725", "title": "Nonlinear (amplified) relationship between nuclear occupancy by triiodothyronine and the appearance rate of hepatic alpha-glycerophosphate dehydrogenase and malic enzyme in the rat.", "content": "Three separate approaches were applied to examine the general relationship between R, the rate of induction of specific enzymes (mitochondrial alpha-glycero-phosphate dehydrogenase and cytosolic malic enzyme) and q, the fractional nuclear occupancy by triiodothyronine in male Sprague-Dawley rats. Daily 200-microgram injections of triiodothyronine per 10u g body wt for 7 days resulted in saturation of the hepatic nuclear sites and the achievement of an apparent new steady state of enzyme levels. The increase achieved over base-line hypothyroid levels was then compared with the increment over hypothyroid base line characteristic of intact euthyroid animals with 47% of nuclear sites occupied. The maximal theoretical reate of steady-state enzyme induction could be protected on the basis of the observed maximal increase in enzyme activity observed 1 day after the injection of graded doses of hormone and lambda, the known fractional rate of enzyme dissipation. The 24-h dose-response studies were used to generate R as a continuous function of q, both in hypothyroid as well as in euthyroid animals. This approach involved the numerical solution of an ordinary differential equation describing the rate of change of enzyme as a function of R, which was assumed to be uniquely related to q. Results of these analyses indicated that the ratio of the maximal rate of induction of enzyme at full occupancy to the rate of induction under euthyroid conditions assumes a value between 9.0 and 19.5, depending on the precise analytic and experimental approach applied. This value is far in excess of the theoretical ratio 2.13 which on would anticipate if R were linearly related to q and 47% of the nuclear sites occupied under physiological conditions. Thus, the signal for enzyme induction appears to undergo progressjive amplification with increasing nuclear occupancy. Moreover, the curve describing the relationship between R and q appears highly nonlinear throughout (concave upwards). Although the molecular mechanism responsible for amplification is unknown, recognition of this phenomenon may be helpful in understanding tissue effects of thyroid hormone excess. Moreover, the analytic technique for determining R as a function of q may be of general applicability in studying hormonal response systems under nonsteady-state conditions.", "contents": "Nonlinear (amplified) relationship between nuclear occupancy by triiodothyronine and the appearance rate of hepatic alpha-glycerophosphate dehydrogenase and malic enzyme in the rat. Three separate approaches were applied to examine the general relationship between R, the rate of induction of specific enzymes (mitochondrial alpha-glycero-phosphate dehydrogenase and cytosolic malic enzyme) and q, the fractional nuclear occupancy by triiodothyronine in male Sprague-Dawley rats. Daily 200-microgram injections of triiodothyronine per 10u g body wt for 7 days resulted in saturation of the hepatic nuclear sites and the achievement of an apparent new steady state of enzyme levels. The increase achieved over base-line hypothyroid levels was then compared with the increment over hypothyroid base line characteristic of intact euthyroid animals with 47% of nuclear sites occupied. The maximal theoretical reate of steady-state enzyme induction could be protected on the basis of the observed maximal increase in enzyme activity observed 1 day after the injection of graded doses of hormone and lambda, the known fractional rate of enzyme dissipation. The 24-h dose-response studies were used to generate R as a continuous function of q, both in hypothyroid as well as in euthyroid animals. This approach involved the numerical solution of an ordinary differential equation describing the rate of change of enzyme as a function of R, which was assumed to be uniquely related to q. Results of these analyses indicated that the ratio of the maximal rate of induction of enzyme at full occupancy to the rate of induction under euthyroid conditions assumes a value between 9.0 and 19.5, depending on the precise analytic and experimental approach applied. This value is far in excess of the theoretical ratio 2.13 which on would anticipate if R were linearly related to q and 47% of the nuclear sites occupied under physiological conditions. Thus, the signal for enzyme induction appears to undergo progressjive amplification with increasing nuclear occupancy. Moreover, the curve describing the relationship between R and q appears highly nonlinear throughout (concave upwards). Although the molecular mechanism responsible for amplification is unknown, recognition of this phenomenon may be helpful in understanding tissue effects of thyroid hormone excess. Moreover, the analytic technique for determining R as a function of q may be of general applicability in studying hormonal response systems under nonsteady-state conditions."}
{"id": "PMID:207726", "title": "Characterization of the human platelet alpha-adrenergic receptor. Correlation of [3H]dihydroergocryptine binding with aggregation and adenylate cyclase inhibition.", "content": "Human platelets aggregate and undergo a release reaction when incubated with catecholamines. Indirect evidence indicates that these events are mediated through alpha-adrenergic receptors. We used [(3)H]dihydroergocryptine, an alpha-adrenergic antagonist, to identify binding sites on platelets that have the characteristics of alpha-adrenergic receptors. Catecholamines compete for the binding sites in a stereo-specific manner with the potency series of (-) epinephrine > (-) norepinephrine > (+/-) phenylephrine > (-) isoproterenol. The dissociation constant (K(d)) of (-) epinephrine is 0.34 muM. Binding is saturable using a platelet particulate fraction but not with intact platelets. There are 0.130 pmol binding sites per milligram protein in fresh platelet membranes. This number represents approximately 100 binding sites per platelet. The K(d) for [(3)H]-dihydroergocryptine was 0.003-0.01 muM. The alpha-adrenergic antagonist phentolamine (K(d) = 0.0069 muM) was much more potent than the beta-adrenergic antagonist (+/-) propranolol (K(d) = 27 muM) in competing for the binding sites. The binding data were correlated with catecholamine-induced platelet aggregation and inhibition of basal and prostaglandin E(1)-stimulated adenylate cyclase. (-) Epinephrine was more potent than (-) norepinephrine in producing aggregation whereas (-) isoproterenol was ineffective. The threshold dose for inducing aggregation by (-) epinephrine was 0.46 muM. Phentolamine and dihydroergocyrptine blocked this response, whereas (+/-) propranolol had no effect. (-) Epinephrine and (-) norepinephrine inhibited basal and prostaglandin E(1)-stimulated adenylate cyclase in a dose-related manner. The concentration of (-) epinephrine inhibiting adenylate cyclase 50% was 0.7 muM. This inhibition was also blocked by phentolamine and dihydroergocryptine but not by (+/-) propranolol. The specificity of binding and the close correlation with alpha-adrenergic receptor-mediated biochemical and physiological responses suggest that the [(3)H]dihydroergocryptine binding site represents, or is closely related to, the human platelet alpha-adrenergic receptor. The ability to assay this receptor directly and to correlate these data with independently measured sequelae of receptor activation should facilitate increased understanding of the physiology and pathophysiology of the human platelet alpha-adrenergic receptor.", "contents": "Characterization of the human platelet alpha-adrenergic receptor. Correlation of [3H]dihydroergocryptine binding with aggregation and adenylate cyclase inhibition. Human platelets aggregate and undergo a release reaction when incubated with catecholamines. Indirect evidence indicates that these events are mediated through alpha-adrenergic receptors. We used [(3)H]dihydroergocryptine, an alpha-adrenergic antagonist, to identify binding sites on platelets that have the characteristics of alpha-adrenergic receptors. Catecholamines compete for the binding sites in a stereo-specific manner with the potency series of (-) epinephrine > (-) norepinephrine > (+/-) phenylephrine > (-) isoproterenol. The dissociation constant (K(d)) of (-) epinephrine is 0.34 muM. Binding is saturable using a platelet particulate fraction but not with intact platelets. There are 0.130 pmol binding sites per milligram protein in fresh platelet membranes. This number represents approximately 100 binding sites per platelet. The K(d) for [(3)H]-dihydroergocryptine was 0.003-0.01 muM. The alpha-adrenergic antagonist phentolamine (K(d) = 0.0069 muM) was much more potent than the beta-adrenergic antagonist (+/-) propranolol (K(d) = 27 muM) in competing for the binding sites. The binding data were correlated with catecholamine-induced platelet aggregation and inhibition of basal and prostaglandin E(1)-stimulated adenylate cyclase. (-) Epinephrine was more potent than (-) norepinephrine in producing aggregation whereas (-) isoproterenol was ineffective. The threshold dose for inducing aggregation by (-) epinephrine was 0.46 muM. Phentolamine and dihydroergocyrptine blocked this response, whereas (+/-) propranolol had no effect. (-) Epinephrine and (-) norepinephrine inhibited basal and prostaglandin E(1)-stimulated adenylate cyclase in a dose-related manner. The concentration of (-) epinephrine inhibiting adenylate cyclase 50% was 0.7 muM. This inhibition was also blocked by phentolamine and dihydroergocryptine but not by (+/-) propranolol. The specificity of binding and the close correlation with alpha-adrenergic receptor-mediated biochemical and physiological responses suggest that the [(3)H]dihydroergocryptine binding site represents, or is closely related to, the human platelet alpha-adrenergic receptor. The ability to assay this receptor directly and to correlate these data with independently measured sequelae of receptor activation should facilitate increased understanding of the physiology and pathophysiology of the human platelet alpha-adrenergic receptor."}
{"id": "PMID:207727", "title": "Chemiluminescence of human and canine polymorphonuclear leukocytes in the absence of phagocytosis.", "content": "Polymorphonuclear leukocytes (PMNs) have increased oxidative metabolism during phagocytosis and emit light (chemiluminescence, CL) as a result of metabolic activation. The present study examined PMN CL in the absence of phagocytosis using sodium fluoride (NaF), a nonparticulate agent and known stimulator of cellular oxidative metabolism. Normal human and canine PMNs were assayed in a CL spectrometer which permitted continuous sample mixing and constant temperature regulation during CL measurement. PMNs treated with 20 mM NaF demonstrated maximum CL responses of 10,000-20,000 cpm above background, 13-17 min after addition of NaF at 37 degrees C. Temperature regulation of reaction mixtures was found to be a critical factor in assaying PMN CL responses to NaF, because a small decrease in temperature (i.e. 1.5 degrees C) substantially depressed and delayed the CL response. Superoxide anion production correlated closely with CL responses in NaF-treated human PMNs. CL responses were completely suppressed in the presence of the oxidative metabolic inhibitors, iodoacetamide, and N-ethylmalemide; and were partially suppressed in the presence of either superoxide dismutase or sodium azide.CL responses of NaF-treated PMNs were significantly lower than responses generated by PMNs phagocytizing opsonized yeast. When NaF was evaluated for its effect on light generation from a singlet oxygen dependent CL reaction, it was found that NaF did not quench singlet oxygen light. This study demonstrates that PMN CL can occur in the absence of phagocytosis, and it proposes that a nonphagocytic PMN CL assay may be useful in evaluating leukocyte metabolic defects.", "contents": "Chemiluminescence of human and canine polymorphonuclear leukocytes in the absence of phagocytosis. Polymorphonuclear leukocytes (PMNs) have increased oxidative metabolism during phagocytosis and emit light (chemiluminescence, CL) as a result of metabolic activation. The present study examined PMN CL in the absence of phagocytosis using sodium fluoride (NaF), a nonparticulate agent and known stimulator of cellular oxidative metabolism. Normal human and canine PMNs were assayed in a CL spectrometer which permitted continuous sample mixing and constant temperature regulation during CL measurement. PMNs treated with 20 mM NaF demonstrated maximum CL responses of 10,000-20,000 cpm above background, 13-17 min after addition of NaF at 37 degrees C. Temperature regulation of reaction mixtures was found to be a critical factor in assaying PMN CL responses to NaF, because a small decrease in temperature (i.e. 1.5 degrees C) substantially depressed and delayed the CL response. Superoxide anion production correlated closely with CL responses in NaF-treated human PMNs. CL responses were completely suppressed in the presence of the oxidative metabolic inhibitors, iodoacetamide, and N-ethylmalemide; and were partially suppressed in the presence of either superoxide dismutase or sodium azide.CL responses of NaF-treated PMNs were significantly lower than responses generated by PMNs phagocytizing opsonized yeast. When NaF was evaluated for its effect on light generation from a singlet oxygen dependent CL reaction, it was found that NaF did not quench singlet oxygen light. This study demonstrates that PMN CL can occur in the absence of phagocytosis, and it proposes that a nonphagocytic PMN CL assay may be useful in evaluating leukocyte metabolic defects."}
{"id": "PMID:207728", "title": "Prevention and reversal of cholera enterotoxin effects in rabbit jejunum by nicotinic acid.", "content": "The cholera enterotoxin produces intestinal secretion associated with an elevation of tissue levels of cyclic adenosine 3',5'-monophosphate levels of cyclic adenosine 3',5'-monosphosphate (cAMP). The objectives of this study were to determine whether intestinal secretion and cAMP elevation induced by cholera toxin could be prevented, or once initiated, reversed by nicotinic acid, an agent known to lower tissue levels of cAMP. In rabbits, four jejunal loops were constructed as alternating control (3-ml isotonic electrolyte solution) and cholera toxin (same solution containing 50 mug purified cholera toxin) loops. Net intestinal secretion was determined by measuring fluid accumulation, after which intestinal biopsies were taken for cAMP assay. The animals were pretreated either subcutaneously with 50 mg/kg nicotinic acid in saline 3 h and 1 h before the introduction of cholera toxin, or intraluminally with 200 mg/kg nicotinic acid in Ringer's lactate solution 15 min before the instillation of cholera toxin. Under these conditions, nicotinic acid blocked the cholera toxin-induced secretion and the rise in cAMP measured 3 h after the loops were exposed to cholera toxin. The effect of the nicotinic acid administered within the lumen on net intestinal secretion was studied. Maximal inhibition of net intestinal secretion was achieved with an intraluminally administered dose of nicotinic acid of 100 mg/kg. This dose was chosen for testing the ability of nicotinic acid to reverse the effects of cholera toxin. When nicotinic acid was instilled into a fifth loop constructed distally to the four experimental loops 3 h after exposure of these loops to cholera toxin, both intestinal secretion and elevation of cAMP were reversed. These results suggest that nicotinic acid can prevent and reverse the secretory effects of cholera toxin and may have a role in the therapy of cholera and other cAMP-associated diarrheal diseases.", "contents": "Prevention and reversal of cholera enterotoxin effects in rabbit jejunum by nicotinic acid. The cholera enterotoxin produces intestinal secretion associated with an elevation of tissue levels of cyclic adenosine 3',5'-monophosphate levels of cyclic adenosine 3',5'-monosphosphate (cAMP). The objectives of this study were to determine whether intestinal secretion and cAMP elevation induced by cholera toxin could be prevented, or once initiated, reversed by nicotinic acid, an agent known to lower tissue levels of cAMP. In rabbits, four jejunal loops were constructed as alternating control (3-ml isotonic electrolyte solution) and cholera toxin (same solution containing 50 mug purified cholera toxin) loops. Net intestinal secretion was determined by measuring fluid accumulation, after which intestinal biopsies were taken for cAMP assay. The animals were pretreated either subcutaneously with 50 mg/kg nicotinic acid in saline 3 h and 1 h before the introduction of cholera toxin, or intraluminally with 200 mg/kg nicotinic acid in Ringer's lactate solution 15 min before the instillation of cholera toxin. Under these conditions, nicotinic acid blocked the cholera toxin-induced secretion and the rise in cAMP measured 3 h after the loops were exposed to cholera toxin. The effect of the nicotinic acid administered within the lumen on net intestinal secretion was studied. Maximal inhibition of net intestinal secretion was achieved with an intraluminally administered dose of nicotinic acid of 100 mg/kg. This dose was chosen for testing the ability of nicotinic acid to reverse the effects of cholera toxin. When nicotinic acid was instilled into a fifth loop constructed distally to the four experimental loops 3 h after exposure of these loops to cholera toxin, both intestinal secretion and elevation of cAMP were reversed. These results suggest that nicotinic acid can prevent and reverse the secretory effects of cholera toxin and may have a role in the therapy of cholera and other cAMP-associated diarrheal diseases."}
{"id": "PMID:207729", "title": "Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage.", "content": "During hemodialysis, alternative pathway complement activation leads to pulmonary sequestration of granulocytes, with loss of pulmonary vascular endothelial integrity and, at times, protein-rich pulmonary edema. An in vitro model of this phenomenon was constructed utilizing 51Cr-labeled human umbilical vein endothelial cell cultures. In this system, granulocytes, when exposed to activated complement (C), induce endothelial damage; this injury is mediated primarily by oxygen radicals produced by the granulocytes. C5a appears to be the C component responsible for granulocyte-induced cytotoxicity; studies with cytochalasin B-treated granulocytes suggest that close approximation of the granulocytes and endothelial cells is necessary for maximal cell injury.", "contents": "Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage. During hemodialysis, alternative pathway complement activation leads to pulmonary sequestration of granulocytes, with loss of pulmonary vascular endothelial integrity and, at times, protein-rich pulmonary edema. An in vitro model of this phenomenon was constructed utilizing 51Cr-labeled human umbilical vein endothelial cell cultures. In this system, granulocytes, when exposed to activated complement (C), induce endothelial damage; this injury is mediated primarily by oxygen radicals produced by the granulocytes. C5a appears to be the C component responsible for granulocyte-induced cytotoxicity; studies with cytochalasin B-treated granulocytes suggest that close approximation of the granulocytes and endothelial cells is necessary for maximal cell injury."}
{"id": "PMID:207730", "title": "Termination of the respiratory burst in human neutrophils.", "content": "Recent evidence has suggested that a particulate O(2) (-)-forming system is responsible for the respiratory burst in activated neutrophils. The respiratory burst is normally a transient event, lasting only 30-60 min. To investigate the mechanism by which the burst is terminated, we examined the O(2) (-)-forming activity of neutrophil particles as a function of time in the presence and absence of agents known to affect the function of intact cells. Measurements of the O(2) (-)-forming capacity of the particles against time of exposure of neutrophils to opsonized zymosan, a potent stimulating agent, revealed a rapid fall in activity when exposure was continued beyond 3 min. Exposure to zymosan under conditions in which the myeloperoxidase system was inactive (i.e., in the presence of myeloperoxidase inhibitors, or in the absence of oxygen) resulted in a substantial increase in the initial O(2) (-)-forming activity of particles from the zymosan-treated cells, but did not prevent the sharp fall in activity seen when zymosan exposure exceeded 10 min. The fall in activity was, however, prevented when activation took place in the presence of cytochalasin B (1.5 mug/ml), an agent thought to act largely by paralyzing the neutrophil through an interaction with its microfilament network.We conclude from these findings that the termination of the respiratory burst results at least in part from the inactivation of the particulate O(2) (-)-forming system. This inactivation involves at least two processes which probably act simultaneously. One is the destruction of the system through the action of myeloperoxidase. The other appears to require active cell motility and is independent of oxygen. The current view holds that the O(2) (-)-forming system of the neutrophil is located in the plasma membrane. It may be that the second process involves the internalization and degradation of this membrane-bound system.", "contents": "Termination of the respiratory burst in human neutrophils. Recent evidence has suggested that a particulate O(2) (-)-forming system is responsible for the respiratory burst in activated neutrophils. The respiratory burst is normally a transient event, lasting only 30-60 min. To investigate the mechanism by which the burst is terminated, we examined the O(2) (-)-forming activity of neutrophil particles as a function of time in the presence and absence of agents known to affect the function of intact cells. Measurements of the O(2) (-)-forming capacity of the particles against time of exposure of neutrophils to opsonized zymosan, a potent stimulating agent, revealed a rapid fall in activity when exposure was continued beyond 3 min. Exposure to zymosan under conditions in which the myeloperoxidase system was inactive (i.e., in the presence of myeloperoxidase inhibitors, or in the absence of oxygen) resulted in a substantial increase in the initial O(2) (-)-forming activity of particles from the zymosan-treated cells, but did not prevent the sharp fall in activity seen when zymosan exposure exceeded 10 min. The fall in activity was, however, prevented when activation took place in the presence of cytochalasin B (1.5 mug/ml), an agent thought to act largely by paralyzing the neutrophil through an interaction with its microfilament network.We conclude from these findings that the termination of the respiratory burst results at least in part from the inactivation of the particulate O(2) (-)-forming system. This inactivation involves at least two processes which probably act simultaneously. One is the destruction of the system through the action of myeloperoxidase. The other appears to require active cell motility and is independent of oxygen. The current view holds that the O(2) (-)-forming system of the neutrophil is located in the plasma membrane. It may be that the second process involves the internalization and degradation of this membrane-bound system."}
{"id": "PMID:207731", "title": "Selective release of excreted DNA sequences from phytohemagglutinin-stimulated human peripheral blood lymphocytes. Effects of trypsin and divalent cations.", "content": "We studied the synthesis of excreted DNA sequences and their release from phytohemagglutinin-stimulated human peripheral blood lymphocytes under conditions permitting optimal cell growth. Cells were labeled by constant exposure to low specific activity [3H]thymidine. Excreted DNA sequences were synthesized during the period of logarithmic cell growth and moved slowly from the high molecular weight chromosomal DNA fraction into the low molecular weight cell DNA fraction (Hirt supernate) from which they could be specifically released by treating the cells briefly with small amounts of various proteases; 1 microgram/ml trypsin for 5 min was optimal. On day 5 of culture, 13.3 +/- 6.9% of the total cellular acid-precipitable [3H]thymidine was released by this treatment. Trypsin-induced release was partially and reversibly inhibited by incubating the cells for 16 h with 5 mM dibutyryl-cyclic AMP. Cells incubated in the absence of divalent cations spontaneously released this Hirt supernatant DNA; after maximal release had occurred under these circumstances, additional trypsin treatment caused no further release of DNA. Trypsin-induced DNA release could be completely and reversibly inhibited by incubating the cells in the presence of 10 mM calcium. Trypsin-released DNA was isolated and analyzed by reassociation kinetics. A major component, representing 54% of the DNA, reassociated with a C0t1/2 of 68 mol.s/liter (the value at which DNA association is 50% complete). The reassociation of this DNA was studied in the presence of an excess of DNA isolated from stimulated lymphocytes on day 3 in culture, and in the presence of an excess of resting lymphocyte DNA. The high molecular weight fraction of day-3 cell DNA contained three times more copies of the trypsin-released DNA major component as compared to resting lymphocyte DNA. Hirt supernatant DNA isolated from day-5 stimulated lymphocytes reassociated in an intermediate component representing 34% of the DNA with a Cot1/2 of mol.s/liter; after cells were treated with trypsin, this component could no longer be identified in the Hirt supernatant fraction, presumably because it had been released into the incubation medium. These data describe a quantitatively reproducible system with which synthesis and release of excreted DNA sequences can be studied.", "contents": "Selective release of excreted DNA sequences from phytohemagglutinin-stimulated human peripheral blood lymphocytes. Effects of trypsin and divalent cations. We studied the synthesis of excreted DNA sequences and their release from phytohemagglutinin-stimulated human peripheral blood lymphocytes under conditions permitting optimal cell growth. Cells were labeled by constant exposure to low specific activity [3H]thymidine. Excreted DNA sequences were synthesized during the period of logarithmic cell growth and moved slowly from the high molecular weight chromosomal DNA fraction into the low molecular weight cell DNA fraction (Hirt supernate) from which they could be specifically released by treating the cells briefly with small amounts of various proteases; 1 microgram/ml trypsin for 5 min was optimal. On day 5 of culture, 13.3 +/- 6.9% of the total cellular acid-precipitable [3H]thymidine was released by this treatment. Trypsin-induced release was partially and reversibly inhibited by incubating the cells for 16 h with 5 mM dibutyryl-cyclic AMP. Cells incubated in the absence of divalent cations spontaneously released this Hirt supernatant DNA; after maximal release had occurred under these circumstances, additional trypsin treatment caused no further release of DNA. Trypsin-induced DNA release could be completely and reversibly inhibited by incubating the cells in the presence of 10 mM calcium. Trypsin-released DNA was isolated and analyzed by reassociation kinetics. A major component, representing 54% of the DNA, reassociated with a C0t1/2 of 68 mol.s/liter (the value at which DNA association is 50% complete). The reassociation of this DNA was studied in the presence of an excess of DNA isolated from stimulated lymphocytes on day 3 in culture, and in the presence of an excess of resting lymphocyte DNA. The high molecular weight fraction of day-3 cell DNA contained three times more copies of the trypsin-released DNA major component as compared to resting lymphocyte DNA. Hirt supernatant DNA isolated from day-5 stimulated lymphocytes reassociated in an intermediate component representing 34% of the DNA with a Cot1/2 of mol.s/liter; after cells were treated with trypsin, this component could no longer be identified in the Hirt supernatant fraction, presumably because it had been released into the incubation medium. These data describe a quantitatively reproducible system with which synthesis and release of excreted DNA sequences can be studied."}
{"id": "PMID:207732", "title": "Bioenergetic pattern of isolated type II pneumocytes in air and during hypoxia.", "content": "The bioenergetic pattern of a cell clone derived from rat lung with ultrastructural and biochemical characteristics like those of type II pneumocytes (T-II-P), has been studied in a tissue culture system. During air cultivation, these cells have a high rate of aerobic and anaerobic glycolysis associated with high activities of two rate-limiting enzymes in glycolysis (pyruvate kinase [PyKi] and phosphofructokinase [PFK]). This is present despite the rates of oxygen consumption and activities of cytochrome oxidase (CyOx) similar to other lung cells. Presumably the high rate of aerobic glycolysis explains the substantial lactate production previously described in lung slices and in the intact perfused lung. Hypoxic cultivation results in a decrease in CyOx. Acute re-exposure to air does not restore the oxygen consumption to normal, presumably as a result of decreased mitochondrial O(2) utilization associated with decreased CyOx activity. As a result, hypoxically cultivated T-II-P cells have a decreased capacity for mitochondrial ATP generation in air as compared to air-cultivated cells. During hypoxia, aerobic and anaerobic glycolysis are further increased as well as the activities of PyKi and PFK. The high rate of glycolysis and high activities of PyKi and PFK in cultivated T-II-P appear to reflect intrinsic genetic regulation. The decreased CyOx activity and increased PyKi and PFK activities in hypoxic T-II-P appear to reflect alterations in enzyme biosynthesis/biodegradation regulated by O(2) availability.", "contents": "Bioenergetic pattern of isolated type II pneumocytes in air and during hypoxia. The bioenergetic pattern of a cell clone derived from rat lung with ultrastructural and biochemical characteristics like those of type II pneumocytes (T-II-P), has been studied in a tissue culture system. During air cultivation, these cells have a high rate of aerobic and anaerobic glycolysis associated with high activities of two rate-limiting enzymes in glycolysis (pyruvate kinase [PyKi] and phosphofructokinase [PFK]). This is present despite the rates of oxygen consumption and activities of cytochrome oxidase (CyOx) similar to other lung cells. Presumably the high rate of aerobic glycolysis explains the substantial lactate production previously described in lung slices and in the intact perfused lung. Hypoxic cultivation results in a decrease in CyOx. Acute re-exposure to air does not restore the oxygen consumption to normal, presumably as a result of decreased mitochondrial O(2) utilization associated with decreased CyOx activity. As a result, hypoxically cultivated T-II-P cells have a decreased capacity for mitochondrial ATP generation in air as compared to air-cultivated cells. During hypoxia, aerobic and anaerobic glycolysis are further increased as well as the activities of PyKi and PFK. The high rate of glycolysis and high activities of PyKi and PFK in cultivated T-II-P appear to reflect intrinsic genetic regulation. The decreased CyOx activity and increased PyKi and PFK activities in hypoxic T-II-P appear to reflect alterations in enzyme biosynthesis/biodegradation regulated by O(2) availability."}
{"id": "PMID:207733", "title": "Contributions of plasma triiodothyronine and local thyroxine monodeiodination to triiodothyronine to nuclear triiodothyronine receptor saturation in pituitary, liver, and kidney of hypothyroid rats. Further evidence relating saturation of pituitary nuclear triiodothyronine receptors and the acute inhibition of thyroid-stimulating hormone release.", "content": "Injections of triiodothyronine (T(3)) and thyroxine (T(4)) into chronically hypothyroid rats were used to evaluate the contribution of intracellular T(4) to T(3) conversion to nuclear T(3) in pituitary, liver, and kidney, and to correlate the occupancy of pituitary nuclear T(3) receptors with inhibition of thyroid-stimulating hormone (TSH) release. Injection of a combination of 70 ng T(3) and 400 ng T(4)/100 g body wt resulted in plasma T(3) concentrations of 45+/-7 ng/dl (mean+/-SD) and 3.0+/-0.4 mug/dl T(4) 3 h later. At that plasma T(3) level, the contribution of plasma T(3) to the nuclear receptor sites resulted in saturation of 34+/-7% for pituitary, 27+/-5% for liver, and 33+/-2% for kidney. In addition to the T(3) derived from plasma T(3), there was additional T(3) derived from intracellular monodeiodination of T(4) in all three tissues that resulted in total nuclear occupancy (as percent saturation) of 58+/-11% (pituitary), 36+/-8% (liver), and 41+/-11% (kidney), respectively. The percent contribution of T(3) derived from cellular T(4) added 41% of the total nuclear T(3) in the pituitary which was significantly higher than the contribution of this source in the liver (24%) or the kidney (19%). 3 h after intravenous injection of increasing doses of T(3), the plasma T(3) concentration correlated well with both the change in TSH and the nuclear occupancy, suggesting a linear relationship between the integrated nuclear occupancy by T(3) and TSH release rate. The contribution of intrapituitary T(4) to T(3) conversion to nuclear T(3) was accompanied by an appropriate decrease in TSH, supporting the biological relevance of nuclear T(3). Pretreatment of the animals with 6-n-propylthiouracil before T(4) injection decreased neither the nuclear T(3) derived from intrapituitary T(4) nor the subsequent decrease in TSH. These results indicate that intracellular monodeiodination of T(4) contributes substantially to the nuclear T(3) in the pituitary of the hypothyroid rat, and suggest a linear inverse relationship between nuclear receptor occupancy by T(3) in the pituitary and TSH release rate. The data further indicate that T(4) to T(3) monodeiodination is considerably more important as a source of nuclear T(3) in the pituitary than in the liver and kidney. This provides a mechanism whereby the TSH secretion could respond promptly to a decrease in thyroid secretion (predominantly T(4)) before a decrease in plasma T(3) would be expected to lead to significant metabolic hypothyroidism.", "contents": "Contributions of plasma triiodothyronine and local thyroxine monodeiodination to triiodothyronine to nuclear triiodothyronine receptor saturation in pituitary, liver, and kidney of hypothyroid rats. Further evidence relating saturation of pituitary nuclear triiodothyronine receptors and the acute inhibition of thyroid-stimulating hormone release. Injections of triiodothyronine (T(3)) and thyroxine (T(4)) into chronically hypothyroid rats were used to evaluate the contribution of intracellular T(4) to T(3) conversion to nuclear T(3) in pituitary, liver, and kidney, and to correlate the occupancy of pituitary nuclear T(3) receptors with inhibition of thyroid-stimulating hormone (TSH) release. Injection of a combination of 70 ng T(3) and 400 ng T(4)/100 g body wt resulted in plasma T(3) concentrations of 45+/-7 ng/dl (mean+/-SD) and 3.0+/-0.4 mug/dl T(4) 3 h later. At that plasma T(3) level, the contribution of plasma T(3) to the nuclear receptor sites resulted in saturation of 34+/-7% for pituitary, 27+/-5% for liver, and 33+/-2% for kidney. In addition to the T(3) derived from plasma T(3), there was additional T(3) derived from intracellular monodeiodination of T(4) in all three tissues that resulted in total nuclear occupancy (as percent saturation) of 58+/-11% (pituitary), 36+/-8% (liver), and 41+/-11% (kidney), respectively. The percent contribution of T(3) derived from cellular T(4) added 41% of the total nuclear T(3) in the pituitary which was significantly higher than the contribution of this source in the liver (24%) or the kidney (19%). 3 h after intravenous injection of increasing doses of T(3), the plasma T(3) concentration correlated well with both the change in TSH and the nuclear occupancy, suggesting a linear relationship between the integrated nuclear occupancy by T(3) and TSH release rate. The contribution of intrapituitary T(4) to T(3) conversion to nuclear T(3) was accompanied by an appropriate decrease in TSH, supporting the biological relevance of nuclear T(3). Pretreatment of the animals with 6-n-propylthiouracil before T(4) injection decreased neither the nuclear T(3) derived from intrapituitary T(4) nor the subsequent decrease in TSH. These results indicate that intracellular monodeiodination of T(4) contributes substantially to the nuclear T(3) in the pituitary of the hypothyroid rat, and suggest a linear inverse relationship between nuclear receptor occupancy by T(3) in the pituitary and TSH release rate. The data further indicate that T(4) to T(3) monodeiodination is considerably more important as a source of nuclear T(3) in the pituitary than in the liver and kidney. This provides a mechanism whereby the TSH secretion could respond promptly to a decrease in thyroid secretion (predominantly T(4)) before a decrease in plasma T(3) would be expected to lead to significant metabolic hypothyroidism."}
{"id": "PMID:207734", "title": "The role of cyclic adenosine monophosphate in adrenergic effects on ventricular vulnerability to fibrillation in the isolated perfused rat heart.", "content": "The relation between myocardial tissue cyclic AMP (cAMP) and the vulnerability to ventricular fibrillation was assessed in the isolated perfused rat heart by measurement of ventricular fibrillation threshold (VFT) and vulnerable period duration (VP). Exogenous dibutyryl cyclic AMP (DBcAMP) reduced VFT and increased VP by a concentration-related action whereas exogenous cAMP did not. Theophylline (1.0 mmol/liter) increased the tissue content of cAMP by 58% (P < 0.001) and caused a leftward shift in the concentration-response curve to DBcAMP. An effect of cAMP on VFT and VP could be shown in the presence of phosphodiesterase inhibition by theophylline. beta-1-Adrenergic receptor blockade with atenolol did not alter the concentration-response curve for VFT when DBcAMP was administered. Epinephrine (100 nmol/liter to 1 mumol/liter) also increased vulnerability to VF; this effect was accompanied by a concentration-related increase in tissue cAMP, but inconsistent changes in tissue ATP, phosphocreatine and potassium. The concentration-response curve of VFT to epinephrine was shifted leftward by theophylline and rightward by atenolol. The increases in vulnerability to fibrillation in the isolated perfused rat heart, in response to DBcAMP, theophylline or epinephrine, could be related more closely to changes of tissue cAMP than to effects on tissue high energy phosphates or potassium. The effect of epinephrine and theophylline on vulnerability to ventricular fibrillation is mediated via alterations in the intracellular level of cAMP in the isolated perfused rat heart.", "contents": "The role of cyclic adenosine monophosphate in adrenergic effects on ventricular vulnerability to fibrillation in the isolated perfused rat heart. The relation between myocardial tissue cyclic AMP (cAMP) and the vulnerability to ventricular fibrillation was assessed in the isolated perfused rat heart by measurement of ventricular fibrillation threshold (VFT) and vulnerable period duration (VP). Exogenous dibutyryl cyclic AMP (DBcAMP) reduced VFT and increased VP by a concentration-related action whereas exogenous cAMP did not. Theophylline (1.0 mmol/liter) increased the tissue content of cAMP by 58% (P < 0.001) and caused a leftward shift in the concentration-response curve to DBcAMP. An effect of cAMP on VFT and VP could be shown in the presence of phosphodiesterase inhibition by theophylline. beta-1-Adrenergic receptor blockade with atenolol did not alter the concentration-response curve for VFT when DBcAMP was administered. Epinephrine (100 nmol/liter to 1 mumol/liter) also increased vulnerability to VF; this effect was accompanied by a concentration-related increase in tissue cAMP, but inconsistent changes in tissue ATP, phosphocreatine and potassium. The concentration-response curve of VFT to epinephrine was shifted leftward by theophylline and rightward by atenolol. The increases in vulnerability to fibrillation in the isolated perfused rat heart, in response to DBcAMP, theophylline or epinephrine, could be related more closely to changes of tissue cAMP than to effects on tissue high energy phosphates or potassium. The effect of epinephrine and theophylline on vulnerability to ventricular fibrillation is mediated via alterations in the intracellular level of cAMP in the isolated perfused rat heart."}
{"id": "PMID:207735", "title": "Identification of a lymphocyte surface receptor for low density lipoprotein inhibitor, an immunoregulatory species of normal human serum low density lipoprotein.", "content": "The present study demonstrates the existence on human peripheral blood lymphocytes of a saturable cell surface receptor for low density lipoprotein inhibitor (LDL-In), a subset of normal human serum low density lipoprotein (LDL) that has been previously demonstrated to suppress selected lymphocyte functions in vivo and in vitro. The binding of radioiodinated LDL-In of demonstrable biological activity occurs rapidly and is quantitatively augmented by prior cultivation of the lymphocytes in lipoprotein-depleted serum, suggesting regulation of receptor density by lipoproteins in vivo. Binding is temperature dependent, facilitated by calcium ions, saturable at 4 degrees C within 40-60 min, and blocked by prior exposure to unlabeled LDL-In. The lymphocyte receptor is trypsin sensitive and regenerates in vitro with a t1/2 of 3.6 h. LDL-In receptors are calculated to have a maximum density of 4,860 +/- 460 per cell if uniformly distributed on all lymphocyte subsets. These receptors have an estimated average association constant of 1.47 X 10(7) liters/mol. When considered in context of the estimated concentration of LDL-In in blood, the receptors should be partially occupied in vivo by endogenous plasma LDL-In. Prior site occupancy inhibition experiments designed to analyze the specificity of LDL-In binding demonstrate that (a) LDL-In is 13.7-fold more effective than whole LDL in blocking the subsequent binding of 125I-LDL-In to cells; and that (b) LDL is 11-fold more effective than LDL-In in blocking the binding of 125I-LKL. This is consistent with the degree of contamination of each lipoprotein with the other lipoprotein. An independent identity of the LDL-In receptor is also supported by observations that in contrast to the previously described LDL receptor, synthesis and expression of the LDL-In receptor on lymphocytes are not suppressed by cultivation of the cells in the presence of 25-hydroxycholesterol and cholesterol. These findings suggest the existence of a previously undescribed and discrete receptor on lymphocytes for LDL-In, and that the modulation of lymphocyte function by LDL-In may be mediated by a specific cell surface receptor pathway.", "contents": "Identification of a lymphocyte surface receptor for low density lipoprotein inhibitor, an immunoregulatory species of normal human serum low density lipoprotein. The present study demonstrates the existence on human peripheral blood lymphocytes of a saturable cell surface receptor for low density lipoprotein inhibitor (LDL-In), a subset of normal human serum low density lipoprotein (LDL) that has been previously demonstrated to suppress selected lymphocyte functions in vivo and in vitro. The binding of radioiodinated LDL-In of demonstrable biological activity occurs rapidly and is quantitatively augmented by prior cultivation of the lymphocytes in lipoprotein-depleted serum, suggesting regulation of receptor density by lipoproteins in vivo. Binding is temperature dependent, facilitated by calcium ions, saturable at 4 degrees C within 40-60 min, and blocked by prior exposure to unlabeled LDL-In. The lymphocyte receptor is trypsin sensitive and regenerates in vitro with a t1/2 of 3.6 h. LDL-In receptors are calculated to have a maximum density of 4,860 +/- 460 per cell if uniformly distributed on all lymphocyte subsets. These receptors have an estimated average association constant of 1.47 X 10(7) liters/mol. When considered in context of the estimated concentration of LDL-In in blood, the receptors should be partially occupied in vivo by endogenous plasma LDL-In. Prior site occupancy inhibition experiments designed to analyze the specificity of LDL-In binding demonstrate that (a) LDL-In is 13.7-fold more effective than whole LDL in blocking the subsequent binding of 125I-LDL-In to cells; and that (b) LDL is 11-fold more effective than LDL-In in blocking the binding of 125I-LKL. This is consistent with the degree of contamination of each lipoprotein with the other lipoprotein. An independent identity of the LDL-In receptor is also supported by observations that in contrast to the previously described LDL receptor, synthesis and expression of the LDL-In receptor on lymphocytes are not suppressed by cultivation of the cells in the presence of 25-hydroxycholesterol and cholesterol. These findings suggest the existence of a previously undescribed and discrete receptor on lymphocytes for LDL-In, and that the modulation of lymphocyte function by LDL-In may be mediated by a specific cell surface receptor pathway."}
{"id": "PMID:207736", "title": "Interacting effects of sulfonylureas and glucose on cyclic AMP metabolism and insulin release in pancreatic islets of the rat.", "content": "The effects of tolbutamide and glibenclamide on the metabolism of cyclic AMP were investigated in pancreatic islets of the rat. Changes in cyclic AMP were assessed by measuring [(3)H]cyclic AMP after labeling of the islets with [2-(3)H]adenine. In the presence of a nonstimulatory concentration of glucose (3.3 mM), both sulfonylureas caused a rapid increase in islet [(3)H]cyclic AMP, which declined within 5 (tolbutamide) or 10 min (glibenclamide). In the absence of glucose, the glibenclamide effect was shortened, but the initial (1 min) response of [(3)H]-cyclic AMP was unaffected. Glucose could be substituted with d-glyceraldehyde but not pyruvate for prolongation of the glibenclamide response. The effect of glucose withdrawal on the glibenclamide response was reproduced by the addition of d-mannoheptulose to glucose containing media. The [(3)H]cyclic AMP response to glibenclamide was influenced by prior exposure of the islets to glucose, a 30-min preincubation with 27.7 mM glucose, enhancing the response to the sulfonylurea over a subsequent 5-min stimulation period. Sulfonylureas exerted their effects at low but not at high glucose concentrations, i.e., shifted the glucose dose-response curve to the left both for [(3)H]cyclic AMP accumulation and insulin release. On the other hand, increasing concentrations of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, progressively augmented the effects of the drugs. Omission of Ca(++) from the incubation media inhibited both the glucose and the sulfonylurea [(3)H]-cyclic AMP and insulin responses. Epinephrine (1 muM) partially inhibited the [(3)H]cyclic AMP response to both glucose and sulfonylurea, whereas insulin release was completely abolished. It is concluded that the sulfonylurea effects on islet cyclic AMP are intimately related to those of glucose. It is suggested that sulfonylureas exert a major part of their action by facilitating the effect of glucose on the beta-cell adenylate cyclase; the increased cyclic AMP level, in its turn, enhances the secretion rate of insulin.", "contents": "Interacting effects of sulfonylureas and glucose on cyclic AMP metabolism and insulin release in pancreatic islets of the rat. The effects of tolbutamide and glibenclamide on the metabolism of cyclic AMP were investigated in pancreatic islets of the rat. Changes in cyclic AMP were assessed by measuring [(3)H]cyclic AMP after labeling of the islets with [2-(3)H]adenine. In the presence of a nonstimulatory concentration of glucose (3.3 mM), both sulfonylureas caused a rapid increase in islet [(3)H]cyclic AMP, which declined within 5 (tolbutamide) or 10 min (glibenclamide). In the absence of glucose, the glibenclamide effect was shortened, but the initial (1 min) response of [(3)H]-cyclic AMP was unaffected. Glucose could be substituted with d-glyceraldehyde but not pyruvate for prolongation of the glibenclamide response. The effect of glucose withdrawal on the glibenclamide response was reproduced by the addition of d-mannoheptulose to glucose containing media. The [(3)H]cyclic AMP response to glibenclamide was influenced by prior exposure of the islets to glucose, a 30-min preincubation with 27.7 mM glucose, enhancing the response to the sulfonylurea over a subsequent 5-min stimulation period. Sulfonylureas exerted their effects at low but not at high glucose concentrations, i.e., shifted the glucose dose-response curve to the left both for [(3)H]cyclic AMP accumulation and insulin release. On the other hand, increasing concentrations of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, progressively augmented the effects of the drugs. Omission of Ca(++) from the incubation media inhibited both the glucose and the sulfonylurea [(3)H]-cyclic AMP and insulin responses. Epinephrine (1 muM) partially inhibited the [(3)H]cyclic AMP response to both glucose and sulfonylurea, whereas insulin release was completely abolished. It is concluded that the sulfonylurea effects on islet cyclic AMP are intimately related to those of glucose. It is suggested that sulfonylureas exert a major part of their action by facilitating the effect of glucose on the beta-cell adenylate cyclase; the increased cyclic AMP level, in its turn, enhances the secretion rate of insulin."}
{"id": "PMID:207737", "title": "Decreased glucagon receptors in diabetic rat hepatocytes. Evidence for regulation of glucagon receptors by hyperglucagonemia.", "content": "The effects of endogenous and exogenous hyperglucagonemia on the specific binding of glucagon to hepatocyte receptors was studied, as was the response of cAMP to glucagon. In streptozotocin diabetic rats, blood glucose and plasma glucagon increased and plasma insulin decreased as compared with controls. Insulin treatment in diabetic rats restored blood glucose and plasma glucagon toward normal and elevated plasma insulin. Specific binding of (125)I-glucagon to isolated hepatocytes (10(6) cells) decreased in diabetic rats (8.17+/-0.38%) compared to controls (14.05+/-0.87%) and was restored by insulin treatment (12.25+/-0.93%). Specific binding of (125)I-insulin in controls was 7.30+/-10.16%; it increased in diabetic rats to 12.50+/-0.86%, and decreased in diabetic rats after insulin treatment (9.08+/-0.87%). Scatchard analysis and the competition plots of the data indicate that decreased glucagon binding and increased insulin binding in diabetes were due to change in the number of receptors rather than a change in their affinity. Hepatocyte cAMP response to glucagon (0.25-5.0 ng/ml) was almost abolished in diabetic rats and was restored with insulin treatment. Specific glucagon binding by hepatocytes from chronically hyperglucagonemic (glucagon injected) rats was decreased (P < 0.005) to 8.76+/-0.61% compared with controls (13.20+/-0.74%) and acutely hyperglucagonemic animals (13.53+/-1.33%). The decreased binding was associated with a 70% decrease in hepatocyte cAMP response to glucagon compared with a normal response in acutely hyperglucagonemic rats.These data appear to support the concept of receptor regulation by ambient hormone level. In both endogenous and exogenous hyperglucagonemia, however, there was a disproportionately large decrease in cAMP response to glucagon compared to the decrease in glucagon binding.", "contents": "Decreased glucagon receptors in diabetic rat hepatocytes. Evidence for regulation of glucagon receptors by hyperglucagonemia. The effects of endogenous and exogenous hyperglucagonemia on the specific binding of glucagon to hepatocyte receptors was studied, as was the response of cAMP to glucagon. In streptozotocin diabetic rats, blood glucose and plasma glucagon increased and plasma insulin decreased as compared with controls. Insulin treatment in diabetic rats restored blood glucose and plasma glucagon toward normal and elevated plasma insulin. Specific binding of (125)I-glucagon to isolated hepatocytes (10(6) cells) decreased in diabetic rats (8.17+/-0.38%) compared to controls (14.05+/-0.87%) and was restored by insulin treatment (12.25+/-0.93%). Specific binding of (125)I-insulin in controls was 7.30+/-10.16%; it increased in diabetic rats to 12.50+/-0.86%, and decreased in diabetic rats after insulin treatment (9.08+/-0.87%). Scatchard analysis and the competition plots of the data indicate that decreased glucagon binding and increased insulin binding in diabetes were due to change in the number of receptors rather than a change in their affinity. Hepatocyte cAMP response to glucagon (0.25-5.0 ng/ml) was almost abolished in diabetic rats and was restored with insulin treatment. Specific glucagon binding by hepatocytes from chronically hyperglucagonemic (glucagon injected) rats was decreased (P < 0.005) to 8.76+/-0.61% compared with controls (13.20+/-0.74%) and acutely hyperglucagonemic animals (13.53+/-1.33%). The decreased binding was associated with a 70% decrease in hepatocyte cAMP response to glucagon compared with a normal response in acutely hyperglucagonemic rats.These data appear to support the concept of receptor regulation by ambient hormone level. In both endogenous and exogenous hyperglucagonemia, however, there was a disproportionately large decrease in cAMP response to glucagon compared to the decrease in glucagon binding."}
{"id": "PMID:207738", "title": "Functional profile of the isolated uremic nephron. Impaired water permeability and adenylate cyclase responsiveness of the cortical collecting tubule to vasopressin.", "content": "Resistance of the chronically diseased kidney to vasopressin has been proposed as a possible explanation for the urinary concentrating defect of uremia. The present studies examined the water permeability and adenylate cyclase responsiveness of isolated cortical collecting tubules (CCT) from remnant kidneys of uremic rabbits to vasopressin. In the absence of vasopressin the CCTs of both normal and uremic rabbits were impermeable to water. At the same osmotic gradient, addition of a supramaximal concentration of vasopressin to the peritubular bathing medium led to a significantly lower net water flux per unit length (and per unit luminal surface area) in uremic CCTs than in normal CCTs. Transepithelial osmotic water permeability coefficient, P(f), was 0.0232 +/-0.0043 cm/s in normal CCTs and 0.0059+/-0.001 cm/s in uremic CCTs (P < 0.001). The impaired vasopressin responsiveness of the uremic CCTs was observed whether normal or uremic serum was present in the bath. Basal adenylate cyclase activity per microgram protein was comparable in normal and uremic CCTs. Stimulation by NaF led to equivalent levels of activity in both, whereas vasopressin-stimulated activity was 50% lower in the uremic than in the normal CCTs (P < 0.025). The cyclic AMP analogue, 8-bromo cyclic AMP, produced an increase in the P(f) of normal CCTs closely comparable to that observed with vasopressin. In contrast, the P(f) of uremic CCTs was only minimally increased by this analogue and was not further stimulated by theophylline. These studies demonstrate an impaired responsiveness of the uremic CCT to vasopressin. This functional defect appears to be a result, at least in part, of a blunted responsiveness of adenylate cyclase to vasopressin. The data further suggest that an additional defect in the cellular response to vasopressin may exist, involving a step (or steps) subsequent to the formation of cyclic AMP.A unifying concept of the urinary concentrating defect of uremia is proposed which incorporates a number of hitherto unexplained observations on the concentrating and diluting functions of the diseased kidney.", "contents": "Functional profile of the isolated uremic nephron. Impaired water permeability and adenylate cyclase responsiveness of the cortical collecting tubule to vasopressin. Resistance of the chronically diseased kidney to vasopressin has been proposed as a possible explanation for the urinary concentrating defect of uremia. The present studies examined the water permeability and adenylate cyclase responsiveness of isolated cortical collecting tubules (CCT) from remnant kidneys of uremic rabbits to vasopressin. In the absence of vasopressin the CCTs of both normal and uremic rabbits were impermeable to water. At the same osmotic gradient, addition of a supramaximal concentration of vasopressin to the peritubular bathing medium led to a significantly lower net water flux per unit length (and per unit luminal surface area) in uremic CCTs than in normal CCTs. Transepithelial osmotic water permeability coefficient, P(f), was 0.0232 +/-0.0043 cm/s in normal CCTs and 0.0059+/-0.001 cm/s in uremic CCTs (P < 0.001). The impaired vasopressin responsiveness of the uremic CCTs was observed whether normal or uremic serum was present in the bath. Basal adenylate cyclase activity per microgram protein was comparable in normal and uremic CCTs. Stimulation by NaF led to equivalent levels of activity in both, whereas vasopressin-stimulated activity was 50% lower in the uremic than in the normal CCTs (P < 0.025). The cyclic AMP analogue, 8-bromo cyclic AMP, produced an increase in the P(f) of normal CCTs closely comparable to that observed with vasopressin. In contrast, the P(f) of uremic CCTs was only minimally increased by this analogue and was not further stimulated by theophylline. These studies demonstrate an impaired responsiveness of the uremic CCT to vasopressin. This functional defect appears to be a result, at least in part, of a blunted responsiveness of adenylate cyclase to vasopressin. The data further suggest that an additional defect in the cellular response to vasopressin may exist, involving a step (or steps) subsequent to the formation of cyclic AMP.A unifying concept of the urinary concentrating defect of uremia is proposed which incorporates a number of hitherto unexplained observations on the concentrating and diluting functions of the diseased kidney."}
{"id": "PMID:207739", "title": "Effects of dietary polyunsaturated and saturated fat on the properties of high density lipoproteins and the metabolism of apolipoprotein A-I.", "content": "In this study we have investigated, in four normal males the effects of dietary saturated and polyunsaturated fat on the chemical composition and thermotropic properties of human high density lipoproteins (HDL) and have measured the influence of the diets on the metabolism of that fraction of HDL apolipoprotein A-I (apoA-I) that undergoes exchange in vitro and accounts for approximately two-thirds of the lipoprotein's apoA-I complement. When compared with the saturated fat diet, the polyunsaturated diet reduced plasma cholesterol (24%, P < 0.01) by affecting the cholesterol content in the very low density lipoprotein ( downward arrow25%, P < 0.02), low density lipoprotein ( downward arrow20%, P < 0.01), and high density lipoprotein fractions ( downward arrow33%, P < 0.01). Plasma triglyceride was also lowered (by 13%, P < 0.01). Furthermore, polyunsaturated fat ingestion caused a significant fall in the palmitate and stearate content of HDL triglyceride (41 and 37%, respectively), cholesteryl esters (29 and 35%), and phospholipids (17 and 9%) with a concomitant increase in the linoleate content of these moieties (157, 28, and 29%, respectively). The polyunsaturated diet also produced reciprocal changes in the percentage protein ( downward arrow9%, P < 0.02) and phospholipid ( downward arrow11.5%, P < 0.01) in HDl. These compositional changes were associated with an increase in the microscopic fluidity of the polyunsaturated HDL, although both diets had little effect on the fluidity parameters of HDL at body temperature. Rate zonal ultracentrifugation indicated that the HDL(2)/HDL(3) ratio fell by 28% (P < 0.05) on the polyunsaturated fat diet. In addition to the above, this diet reduced plasma apoA-I by 21% (P < 0.01). No change was seen in the fractional catabolic rate or the distribution of the apoprotein between intravascular and extravascular compartments on the two diets. However, when compared with the saturated diet, the synthetic rate of apoA-I was reduced by 26% during polyunsaturated fat feeding. The results show that polyunsaturated fat alters the chemical composition, thermotropic properties, and subfraction distribution of HDL without changing the fractional rate of catabolism of their major protein, apoA-I.These findings deserve careful consideration in determining the applicability and efficacy of polyunsaturated fat diet therapy in the prevention of atherosclerosis in man.", "contents": "Effects of dietary polyunsaturated and saturated fat on the properties of high density lipoproteins and the metabolism of apolipoprotein A-I. In this study we have investigated, in four normal males the effects of dietary saturated and polyunsaturated fat on the chemical composition and thermotropic properties of human high density lipoproteins (HDL) and have measured the influence of the diets on the metabolism of that fraction of HDL apolipoprotein A-I (apoA-I) that undergoes exchange in vitro and accounts for approximately two-thirds of the lipoprotein's apoA-I complement. When compared with the saturated fat diet, the polyunsaturated diet reduced plasma cholesterol (24%, P < 0.01) by affecting the cholesterol content in the very low density lipoprotein ( downward arrow25%, P < 0.02), low density lipoprotein ( downward arrow20%, P < 0.01), and high density lipoprotein fractions ( downward arrow33%, P < 0.01). Plasma triglyceride was also lowered (by 13%, P < 0.01). Furthermore, polyunsaturated fat ingestion caused a significant fall in the palmitate and stearate content of HDL triglyceride (41 and 37%, respectively), cholesteryl esters (29 and 35%), and phospholipids (17 and 9%) with a concomitant increase in the linoleate content of these moieties (157, 28, and 29%, respectively). The polyunsaturated diet also produced reciprocal changes in the percentage protein ( downward arrow9%, P < 0.02) and phospholipid ( downward arrow11.5%, P < 0.01) in HDl. These compositional changes were associated with an increase in the microscopic fluidity of the polyunsaturated HDL, although both diets had little effect on the fluidity parameters of HDL at body temperature. Rate zonal ultracentrifugation indicated that the HDL(2)/HDL(3) ratio fell by 28% (P < 0.05) on the polyunsaturated fat diet. In addition to the above, this diet reduced plasma apoA-I by 21% (P < 0.01). No change was seen in the fractional catabolic rate or the distribution of the apoprotein between intravascular and extravascular compartments on the two diets. However, when compared with the saturated diet, the synthetic rate of apoA-I was reduced by 26% during polyunsaturated fat feeding. The results show that polyunsaturated fat alters the chemical composition, thermotropic properties, and subfraction distribution of HDL without changing the fractional rate of catabolism of their major protein, apoA-I.These findings deserve careful consideration in determining the applicability and efficacy of polyunsaturated fat diet therapy in the prevention of atherosclerosis in man."}
{"id": "PMID:207740", "title": "Alteration of the growth of cytomegalovirus and herpes simplex virus type 1 by epidermal growth factor, a contaminant of crude human chorionic gonadotropin preparations.", "content": "Pretreatment (12-48 h) of human fibroblasts with crude, human chorionic gonadotropin (HCG) was found to suppress cytomegalovirus infection and enhance productive herpes simplex type 1 (HSV) infection in vitro. Maximal effect on virus replication occurred at the time of maximal infectivity of control cultures (48 h and 6 days after viral innoculation for HSV and cytomegalovirus, respectively). The alteration in viral growth was not due to the HCG itself, but rather to epidermal growth factor, a contaminant of crude HCG. The effect of epidermal growth factor on viral infectivity was shown to be a cell-mediated event requiring protein synthesis.", "contents": "Alteration of the growth of cytomegalovirus and herpes simplex virus type 1 by epidermal growth factor, a contaminant of crude human chorionic gonadotropin preparations. Pretreatment (12-48 h) of human fibroblasts with crude, human chorionic gonadotropin (HCG) was found to suppress cytomegalovirus infection and enhance productive herpes simplex type 1 (HSV) infection in vitro. Maximal effect on virus replication occurred at the time of maximal infectivity of control cultures (48 h and 6 days after viral innoculation for HSV and cytomegalovirus, respectively). The alteration in viral growth was not due to the HCG itself, but rather to epidermal growth factor, a contaminant of crude HCG. The effect of epidermal growth factor on viral infectivity was shown to be a cell-mediated event requiring protein synthesis."}
{"id": "PMID:207741", "title": "Very low density lipoprotein. Metabolism of phospholipids, cholesterol, and apolipoprotein C in the isolated perfused rat heart.", "content": "The fate of rat plasma very low density lipoprotein (VLDL) constituents was determined in the isolated perfused rat heart. VLDL was labeled with [(14)C]palmitate, (32)P-phospholipids, [(3)H] cholesterol, and (125)I-apolipoprotein C (apoC). Perfusions were performed with an albumin-containing buffer and without plasma. Radioactivity was followed in fractions of d < 1.019, d 1.019-1.04, d 1.04-1.21, and d > 1.21 g/ml, prepared by ultracentrifugation.VLDL triglycerides were progressively hydrolyzed to fatty acids (10-120-min perfusions). Concomitantly, phospholipids, cholesterol (predominantly unesterified), and apoC were removed from the VLDL to all other fractions. About 30-35% of the phosphatidylcholine was hydrolized to lysophosphatidylcholine and was recovered at d > 1.21 g/ml. The phosphatidylcholine-and triglyceride-hydrolyzing activities were confined to membrane supported enzyme(s). The other 60-65% of the phosphatidylcholine was removed unhydrolyzed and was found in fractions of d 1.019-1.04 (10-15%), d 1.04-1.21 (25-30%), and d > 1.21 g/ml (15-20%). [(32)P]Sphingomyelin accumulated at the fraction of d 1.04-1.21 g/ml. Unesterified cholesterol was found in the fraction of d 1.04-1.21 g/ml. ApoC was recovered predominantly in fractions of d 1.04-1.21 (50-60%) and d > 1.21 g/ml (30-40%). Cholesteryl esters were associated with VLDL during the hydrolysis of 50-70% of the triglycerides, but with advanced lipolysis, appeared in higher densities, mainly d 1.019-1.04 g/ml. The fraction of d 1.04-1.21 g/ml, (containing phosphatidylcholine, sphingomyelin, unesterified cholesterol, and apoC) contained by negative staining, many disk-like structures. The study demonstrated that removal of surface constituents (phospholipids, unesterified cholesterol, and apoC) during lipolysis of VLDL is an intrinsic feature of the lipolytic process, and is independent of the presence of plasma. It also indicated that surface constituents may be removed in a particulated form.", "contents": "Very low density lipoprotein. Metabolism of phospholipids, cholesterol, and apolipoprotein C in the isolated perfused rat heart. The fate of rat plasma very low density lipoprotein (VLDL) constituents was determined in the isolated perfused rat heart. VLDL was labeled with [(14)C]palmitate, (32)P-phospholipids, [(3)H] cholesterol, and (125)I-apolipoprotein C (apoC). Perfusions were performed with an albumin-containing buffer and without plasma. Radioactivity was followed in fractions of d < 1.019, d 1.019-1.04, d 1.04-1.21, and d > 1.21 g/ml, prepared by ultracentrifugation.VLDL triglycerides were progressively hydrolyzed to fatty acids (10-120-min perfusions). Concomitantly, phospholipids, cholesterol (predominantly unesterified), and apoC were removed from the VLDL to all other fractions. About 30-35% of the phosphatidylcholine was hydrolized to lysophosphatidylcholine and was recovered at d > 1.21 g/ml. The phosphatidylcholine-and triglyceride-hydrolyzing activities were confined to membrane supported enzyme(s). The other 60-65% of the phosphatidylcholine was removed unhydrolyzed and was found in fractions of d 1.019-1.04 (10-15%), d 1.04-1.21 (25-30%), and d > 1.21 g/ml (15-20%). [(32)P]Sphingomyelin accumulated at the fraction of d 1.04-1.21 g/ml. Unesterified cholesterol was found in the fraction of d 1.04-1.21 g/ml. ApoC was recovered predominantly in fractions of d 1.04-1.21 (50-60%) and d > 1.21 g/ml (30-40%). Cholesteryl esters were associated with VLDL during the hydrolysis of 50-70% of the triglycerides, but with advanced lipolysis, appeared in higher densities, mainly d 1.019-1.04 g/ml. The fraction of d 1.04-1.21 g/ml, (containing phosphatidylcholine, sphingomyelin, unesterified cholesterol, and apoC) contained by negative staining, many disk-like structures. The study demonstrated that removal of surface constituents (phospholipids, unesterified cholesterol, and apoC) during lipolysis of VLDL is an intrinsic feature of the lipolytic process, and is independent of the presence of plasma. It also indicated that surface constituents may be removed in a particulated form."}
{"id": "PMID:207742", "title": "The inhibition of polymorphonuclear leukocyte cytotoxicity by dapsone. A possible mechanism in the treatment of dermatitis herpetiformis.", "content": "The effect of the sulfone compound 4,4'-diaminodiphenyl sulfone (dapsone) on normal human polymorphonuclear leukocytes (PMNL) has been investigated in vitro. The drug has a dramatically beneficial effect in dermatitis herpetiformis in which the PMNL and immune complexes has been stressed to be of importance for the development of the skin lesions. Pruritus disappears and the inflammatory eruptions clear within a few days of starting therapy. The effect of dapsone has been evaluated on the different stages of phagocytosis. Using dapsone concentrations (1-30 mug/ml) comparable with those found after therapeutic doses, we have found that the drug interferes primarily with the myeloperoxidase (MPO)-H(2)O(2)-halide-mediated cytotoxic system in the PMNL. No effect was observed on random locomotion, chemotaxis, phagocytic ingestion, oxidative metabolism, or the release of lysosomal enzymes. Kinetic studies in a cell-free system with purified MPO revealed a competitive type of inhibition using varying concentrations of NaI. Furthermore, the inhibition resulted in reduced candidicidal activity during phagocytosis of Candida albicans, and reduced cytotoxicity to adjacent mammalian cells measured as the (51)Cr release from virus-induced lymphoma cells. Because the MPO-H(2)O(2)-halide system not only fulfills the antimicrobial activity but is suggested to be a modulator of the inflammatory reaction as well, the action of dapsone in dermatitis herpetiformis may in part be explained by its effect on this system.", "contents": "The inhibition of polymorphonuclear leukocyte cytotoxicity by dapsone. A possible mechanism in the treatment of dermatitis herpetiformis. The effect of the sulfone compound 4,4'-diaminodiphenyl sulfone (dapsone) on normal human polymorphonuclear leukocytes (PMNL) has been investigated in vitro. The drug has a dramatically beneficial effect in dermatitis herpetiformis in which the PMNL and immune complexes has been stressed to be of importance for the development of the skin lesions. Pruritus disappears and the inflammatory eruptions clear within a few days of starting therapy. The effect of dapsone has been evaluated on the different stages of phagocytosis. Using dapsone concentrations (1-30 mug/ml) comparable with those found after therapeutic doses, we have found that the drug interferes primarily with the myeloperoxidase (MPO)-H(2)O(2)-halide-mediated cytotoxic system in the PMNL. No effect was observed on random locomotion, chemotaxis, phagocytic ingestion, oxidative metabolism, or the release of lysosomal enzymes. Kinetic studies in a cell-free system with purified MPO revealed a competitive type of inhibition using varying concentrations of NaI. Furthermore, the inhibition resulted in reduced candidicidal activity during phagocytosis of Candida albicans, and reduced cytotoxicity to adjacent mammalian cells measured as the (51)Cr release from virus-induced lymphoma cells. Because the MPO-H(2)O(2)-halide system not only fulfills the antimicrobial activity but is suggested to be a modulator of the inflammatory reaction as well, the action of dapsone in dermatitis herpetiformis may in part be explained by its effect on this system."}
{"id": "PMID:207744", "title": "The need for color coding in ultrasound mammography.", "content": "The correct interpretation of echo amplitude patterns of high-resolution gray scale ultrasonograms of the breast requires the use of calibrated color-coded isodensitometry, standardized operation of the ultrasound system, amplitude stability of 1 per cent or better, and a constant velocity water-coupled electro-mechanical scanner. The same conditions may be required for correct interpretation of the ultrasonograms of the parenchyma of the liver, spleen, ovaries, testes, uterus, thyroid, and tumors. Color coding is not required and may actually be detrimental in the study of gross ultrasonography anatomy and in disease states that can be identified by simple anatomical distortions. To be of value, rigid standardization and control of the amplitude characteristics and scanning velocity of the system are imperative.", "contents": "The need for color coding in ultrasound mammography. The correct interpretation of echo amplitude patterns of high-resolution gray scale ultrasonograms of the breast requires the use of calibrated color-coded isodensitometry, standardized operation of the ultrasound system, amplitude stability of 1 per cent or better, and a constant velocity water-coupled electro-mechanical scanner. The same conditions may be required for correct interpretation of the ultrasonograms of the parenchyma of the liver, spleen, ovaries, testes, uterus, thyroid, and tumors. Color coding is not required and may actually be detrimental in the study of gross ultrasonography anatomy and in disease states that can be identified by simple anatomical distortions. To be of value, rigid standardization and control of the amplitude characteristics and scanning velocity of the system are imperative."}
{"id": "PMID:207746", "title": "Histochemical, pharmacological and microspectrofluorometric analysis of new sites of serotonin localization in the rat hypothalamus.", "content": "Histopharmacological and microspectrofluorometric analysis was applied to the rat hypothalamus for the identification of serotonin. Neuronal perikarya, especially certain of those of the endocrinologically important arcuate nucleus, were seen to contain a yellow histofluorescence which possessed spectral characteristics consistent with the serotonin fluorophor. Serotonin was localized also within varicosities of various hypothalamic nuclei, as well as within an ependymally associated network of fibers. Pharmacological administration of the serotonin precursor, tryptophan, resulted in the identification of serotonin histofluorescence and spectra within hypothalamic neurons yielding evidence that these neurons possess the capacity to synthesize serotonin. These newly described cells may be of importance to the regulatin of hypothalamically mediated endocrine function due to their neuroanatomical placement in the medical basal hypothalamus.", "contents": "Histochemical, pharmacological and microspectrofluorometric analysis of new sites of serotonin localization in the rat hypothalamus. Histopharmacological and microspectrofluorometric analysis was applied to the rat hypothalamus for the identification of serotonin. Neuronal perikarya, especially certain of those of the endocrinologically important arcuate nucleus, were seen to contain a yellow histofluorescence which possessed spectral characteristics consistent with the serotonin fluorophor. Serotonin was localized also within varicosities of various hypothalamic nuclei, as well as within an ependymally associated network of fibers. Pharmacological administration of the serotonin precursor, tryptophan, resulted in the identification of serotonin histofluorescence and spectra within hypothalamic neurons yielding evidence that these neurons possess the capacity to synthesize serotonin. These newly described cells may be of importance to the regulatin of hypothalamically mediated endocrine function due to their neuroanatomical placement in the medical basal hypothalamus."}
{"id": "PMID:207751", "title": "Cyclic AMP phosphodiesterase in human lymphocytes and lymphoblasts.", "content": "Cyclic nucleotide phosphodiesterase activities were examined in lymphocytes from 12 transformed human B cell lines, two T cell lines, six patients with lymphocytic leukemia, and 10 normal donors. A consistent difference bwtween cells from the normal and leukemic state was observed. The cyclic AMP phosphodiesterase activity from normal lymphocytes is inhibited greater than 80% by muM cyclic GMP while this concentration of nucleotide has little or no effect on the enzyme from transformed lymphocytic cell lines or from lymphocytic cells of leukemia patients. The reported lack of cyclic GMP phosphodiesterase in human lymphocytes from several sources is confirmed. The apparent absence of a cyclic GMP degradation mechanism and of cyclic GMP control of cyclic AMP hydrolysis may be related to defective lymphocyte growth control.", "contents": "Cyclic AMP phosphodiesterase in human lymphocytes and lymphoblasts. Cyclic nucleotide phosphodiesterase activities were examined in lymphocytes from 12 transformed human B cell lines, two T cell lines, six patients with lymphocytic leukemia, and 10 normal donors. A consistent difference bwtween cells from the normal and leukemic state was observed. The cyclic AMP phosphodiesterase activity from normal lymphocytes is inhibited greater than 80% by muM cyclic GMP while this concentration of nucleotide has little or no effect on the enzyme from transformed lymphocytic cell lines or from lymphocytic cells of leukemia patients. The reported lack of cyclic GMP phosphodiesterase in human lymphocytes from several sources is confirmed. The apparent absence of a cyclic GMP degradation mechanism and of cyclic GMP control of cyclic AMP hydrolysis may be related to defective lymphocyte growth control."}
{"id": "PMID:207752", "title": "Interaction of \"aza\" and \"deaza\" analogs of adenosine cyclic 3', 5'-phosphate with some enzymes of adenosine cyclic 3', 5'-phosphate metabolism: evidence that the lone pair electrons of N-3 are involved in the binding of adenosine cyclic 3', 5'-phosphate to type II adenosine cyclic 3', 5'-phosphate-dependent protein kinase.", "content": "Five hetercyclic analogs of adenosine cyclic 3',5'-phosphate (cyclic AMP) were examined for their ability (1) to stimulate type II cyclic AMP-dependent kinases from bovine brain, bovine heart, and rat liver; (2) to serve as substrates for \"high Km\" (Km for cyclic AMP = 0.13-0.43 mM) cyclic nucleotide phosphodiesterases from bovine heart, rabbit kidney, and rat liver; and (3) to inhibit the hydrolysis of cyclic AMP catalyzed by \"low Km\" (Km for cAMP = 0.32-1.5 muM) cyclic nucleotide phosphodiesterases from bovine brain, bovine heart, dog heart, rabbit liver, rat brain and rat liver. The analogs all had a purine ring system which had been modified by replacement of a ring carbon with nitrogen or vice versa to yield 2-aza-cAMP (7-amino-4-beta-D-ribofuranosylimidazo [4,5-d] -v-triazine cyclic 3',5'-phosphate); 8-aza-cAMP (7-amino-3-beta-D-ribofuranosyl-v-triazolo-[4,5-d]-pyrimidine cyclic 3',5'-phosphate); 1 deaza-cAMP (7-amino-3-beta-D-ribofuranosylimidazo [4,5-b[pyridine cyclic 3',5'-phosphate); 3-deaza-cAMP (4-amino-1-beta-D-ribofuranosylimidazo[4,5-c]pyridine cyclic 3',5'-phosphate) and 7-deaza-cAMP (7-amino-4-beta-D-ribofuranosylpyrrolo[2,3-d]pyrimidine cyclic 3',5'-phosphate).", "contents": "Interaction of \"aza\" and \"deaza\" analogs of adenosine cyclic 3', 5'-phosphate with some enzymes of adenosine cyclic 3', 5'-phosphate metabolism: evidence that the lone pair electrons of N-3 are involved in the binding of adenosine cyclic 3', 5'-phosphate to type II adenosine cyclic 3', 5'-phosphate-dependent protein kinase. Five hetercyclic analogs of adenosine cyclic 3',5'-phosphate (cyclic AMP) were examined for their ability (1) to stimulate type II cyclic AMP-dependent kinases from bovine brain, bovine heart, and rat liver; (2) to serve as substrates for \"high Km\" (Km for cyclic AMP = 0.13-0.43 mM) cyclic nucleotide phosphodiesterases from bovine heart, rabbit kidney, and rat liver; and (3) to inhibit the hydrolysis of cyclic AMP catalyzed by \"low Km\" (Km for cAMP = 0.32-1.5 muM) cyclic nucleotide phosphodiesterases from bovine brain, bovine heart, dog heart, rabbit liver, rat brain and rat liver. The analogs all had a purine ring system which had been modified by replacement of a ring carbon with nitrogen or vice versa to yield 2-aza-cAMP (7-amino-4-beta-D-ribofuranosylimidazo [4,5-d] -v-triazine cyclic 3',5'-phosphate); 8-aza-cAMP (7-amino-3-beta-D-ribofuranosyl-v-triazolo-[4,5-d]-pyrimidine cyclic 3',5'-phosphate); 1 deaza-cAMP (7-amino-3-beta-D-ribofuranosylimidazo [4,5-b[pyridine cyclic 3',5'-phosphate); 3-deaza-cAMP (4-amino-1-beta-D-ribofuranosylimidazo[4,5-c]pyridine cyclic 3',5'-phosphate) and 7-deaza-cAMP (7-amino-4-beta-D-ribofuranosylpyrrolo[2,3-d]pyrimidine cyclic 3',5'-phosphate)."}
{"id": "PMID:207753", "title": "Changes in cGMP and cAMP content in the estrogen-stimulated rat uterus: temporal relationship with other parameters of hormonal stimulation.", "content": "The effect of estradiol-17beta, estriol, diethylstilbestrol and nafoxidine on rat uterine cGMP content was studied in relation with their respective estrogenic potency. Confirming previous results from Kuehl et al. (5), we observed a rise in uterine cGMP and a simultaneous decrease in cAMP content in treated animals. The reverse effect was obtained in the vagina after stimulation with estradiol or estriol. In the uterus, all compounds tested induced two main waves of cGMP increase corresponding to the two main phases of the estrogenic response i.e. the early fluid imbibition and the later period of true growth. No direct relationship could be established between the late rise in cGMP and true growth responses. A causal link between the first accumulation of uterine cGMP and the wet weight response in the early phase of estrogenic action is suggested by the comparison of time-course effects of the different compounds used on those two parameters.", "contents": "Changes in cGMP and cAMP content in the estrogen-stimulated rat uterus: temporal relationship with other parameters of hormonal stimulation. The effect of estradiol-17beta, estriol, diethylstilbestrol and nafoxidine on rat uterine cGMP content was studied in relation with their respective estrogenic potency. Confirming previous results from Kuehl et al. (5), we observed a rise in uterine cGMP and a simultaneous decrease in cAMP content in treated animals. The reverse effect was obtained in the vagina after stimulation with estradiol or estriol. In the uterus, all compounds tested induced two main waves of cGMP increase corresponding to the two main phases of the estrogenic response i.e. the early fluid imbibition and the later period of true growth. No direct relationship could be established between the late rise in cGMP and true growth responses. A causal link between the first accumulation of uterine cGMP and the wet weight response in the early phase of estrogenic action is suggested by the comparison of time-course effects of the different compounds used on those two parameters."}
{"id": "PMID:207754", "title": "Endogenous GTP and the regulation of epinephrine stimulation of adenylate cyclase.", "content": "Epinephrine increased adenylate cyclase activity 10 to 15 fold in lysates of the cultured human astrocytoma cell line 132-1N1. GTP had little effect on adenylate cyclase activity of lysed cell preparations either with or without added epinephrine. However, the epinephrine stimulation of adenylate cyclase was essentially lost (less than 90%) when a washed nuclei-free membrane preparation of the cyclase was assayed. A 10 to 15 fold epinephrine stimulation of the membrane adenylate cyclase could be demonstrated if cytosol of GTP were added to the assay with the hormone. The criteria of anion exchange, cation exchange, gel exclusion and paper chromatography indicated that the cytosolic agents which acted synergistically with hormones were GTP and GDP. The apparent Kact's for the synergistic action of GDP and GTP were essentially identical (1.0 muM) and of all the other nucleotides examined only GDP had a potency similar to GTP. However, the effect of GDP was apparently due to its rapid conversion to GTP even in the absence of a regenerating system. With epinephrine pretreatment of the intact 132-1N1 cells there was a specific loss of epinephrine stimulation of adenylate cyclase activity. The hormone pretreatment did not alter the capacity of the cytosol from these desensitized cells to potentiate epinephrine stimulation of the cyclase. Rather, the alteration was in the particulate fraction of the lysate. The desensitization of the membranous cyclase was stable and not reversed by GTP.", "contents": "Endogenous GTP and the regulation of epinephrine stimulation of adenylate cyclase. Epinephrine increased adenylate cyclase activity 10 to 15 fold in lysates of the cultured human astrocytoma cell line 132-1N1. GTP had little effect on adenylate cyclase activity of lysed cell preparations either with or without added epinephrine. However, the epinephrine stimulation of adenylate cyclase was essentially lost (less than 90%) when a washed nuclei-free membrane preparation of the cyclase was assayed. A 10 to 15 fold epinephrine stimulation of the membrane adenylate cyclase could be demonstrated if cytosol of GTP were added to the assay with the hormone. The criteria of anion exchange, cation exchange, gel exclusion and paper chromatography indicated that the cytosolic agents which acted synergistically with hormones were GTP and GDP. The apparent Kact's for the synergistic action of GDP and GTP were essentially identical (1.0 muM) and of all the other nucleotides examined only GDP had a potency similar to GTP. However, the effect of GDP was apparently due to its rapid conversion to GTP even in the absence of a regenerating system. With epinephrine pretreatment of the intact 132-1N1 cells there was a specific loss of epinephrine stimulation of adenylate cyclase activity. The hormone pretreatment did not alter the capacity of the cytosol from these desensitized cells to potentiate epinephrine stimulation of the cyclase. Rather, the alteration was in the particulate fraction of the lysate. The desensitization of the membranous cyclase was stable and not reversed by GTP."}
{"id": "PMID:207755", "title": "Loss of lymphocyte cyclic AMP dependent protein kinase activity in malignant melanoma.", "content": "Cyclic AMP dependent protein kinase activity was depressed in whole thymus and spleen as well as isolated splenic lymphocytes from B16 melanoma bearing C57B1/6J mice as compared to control animals. A similar loss of enzyme activity was observed in human peripheral blood lymphocytes from melanoma bearing patients as compared to normal subjects. An unaltered level of activity in the heart of tumor bearing mice suggested some specificity for the lymphoid system. This depressed enzyme activity was the result of a diminished Vmax for cAMP stimulated calf histone phosphorylation. The tumor bearing state in the mouse was also accompanied by a depletion of small lymphocytes from both thymus and spleen and it is hypothesized that the losses of lymphocytes and cAMP dependent protein kinase activity are related.", "contents": "Loss of lymphocyte cyclic AMP dependent protein kinase activity in malignant melanoma. Cyclic AMP dependent protein kinase activity was depressed in whole thymus and spleen as well as isolated splenic lymphocytes from B16 melanoma bearing C57B1/6J mice as compared to control animals. A similar loss of enzyme activity was observed in human peripheral blood lymphocytes from melanoma bearing patients as compared to normal subjects. An unaltered level of activity in the heart of tumor bearing mice suggested some specificity for the lymphoid system. This depressed enzyme activity was the result of a diminished Vmax for cAMP stimulated calf histone phosphorylation. The tumor bearing state in the mouse was also accompanied by a depletion of small lymphocytes from both thymus and spleen and it is hypothesized that the losses of lymphocytes and cAMP dependent protein kinase activity are related."}
{"id": "PMID:207757", "title": "Primary oat-cell carcinoma of the larynx following supraglottic laryngectomy for squamous-cell carcinoma.", "content": "An extremely rare case is reported of a primary oat-cell carcinoma of the larynx in a 70-year-old man who had been treated eight years previously for squamous-cell carcinoma of the larynx by means of supraglottic laryngectomy. A review of the literature revealed only 5 unequivocal previous reports of this primary oat-cell tumor; the present report makes a total of 6 cases. The morphologic pattern, histogenesis and biologic behavior are discussed. The patient of this report was treated by surgical intervention and radiotherapy. He was well, six months later. Only one of the 5 patients previously reported survived for more than a few months. This type of lesion has a poor prognosis because of its tendency to metastasize early to various organs.", "contents": "Primary oat-cell carcinoma of the larynx following supraglottic laryngectomy for squamous-cell carcinoma. An extremely rare case is reported of a primary oat-cell carcinoma of the larynx in a 70-year-old man who had been treated eight years previously for squamous-cell carcinoma of the larynx by means of supraglottic laryngectomy. A review of the literature revealed only 5 unequivocal previous reports of this primary oat-cell tumor; the present report makes a total of 6 cases. The morphologic pattern, histogenesis and biologic behavior are discussed. The patient of this report was treated by surgical intervention and radiotherapy. He was well, six months later. Only one of the 5 patients previously reported survived for more than a few months. This type of lesion has a poor prognosis because of its tendency to metastasize early to various organs."}
{"id": "PMID:207770", "title": "Fluorescent antibodies and lectins stain intracellular structures in fixed cells treated with nonionic detergent.", "content": "Nonionic detergent (NP40) treatment of paraformaldehyde-fixed normal and SV40-transformed human fibroblasts resulted in intracellular penetration of two chosen fluorescent antibodies and Concanavalin A (Con A). After the detergent treatment nuclear SV40 T antigen, cytoplasmic fibronectin glycoprotein and Con A binding sites could be visualized in fluorescence microscopy. The lowest NP40 concentration which made fixed cells permeable was 0.05%. The morphology of cells was preserved better by this new method than by conventional fixation methods, such as acetone treatment. In scanning electron microscopy the surface of the fixed NP40-treated cells had only small rugosities and fine pores. The subsurface cytoskeleton especially was well preserved and had a more distinct fine structure. The improved morphology made it possible to detect a similar distribution of fibronectin and Con A binding sites in the perinuclear endoplasmic reticulum regions.", "contents": "Fluorescent antibodies and lectins stain intracellular structures in fixed cells treated with nonionic detergent. Nonionic detergent (NP40) treatment of paraformaldehyde-fixed normal and SV40-transformed human fibroblasts resulted in intracellular penetration of two chosen fluorescent antibodies and Concanavalin A (Con A). After the detergent treatment nuclear SV40 T antigen, cytoplasmic fibronectin glycoprotein and Con A binding sites could be visualized in fluorescence microscopy. The lowest NP40 concentration which made fixed cells permeable was 0.05%. The morphology of cells was preserved better by this new method than by conventional fixation methods, such as acetone treatment. In scanning electron microscopy the surface of the fixed NP40-treated cells had only small rugosities and fine pores. The subsurface cytoskeleton especially was well preserved and had a more distinct fine structure. The improved morphology made it possible to detect a similar distribution of fibronectin and Con A binding sites in the perinuclear endoplasmic reticulum regions."}
{"id": "PMID:207771", "title": "An efficient method of antibody elution for the successive or simultaneous localization of two antigens by immunocytochemistry.", "content": "The method described in this paper is available for removal of antibodies retained by tissue antigen after immunohistochemical staining. Its application to the antehypophysis has allowed the successive or the simultaneous localization of two different hormones.", "contents": "An efficient method of antibody elution for the successive or simultaneous localization of two antigens by immunocytochemistry. The method described in this paper is available for removal of antibodies retained by tissue antigen after immunohistochemical staining. Its application to the antehypophysis has allowed the successive or the simultaneous localization of two different hormones."}
{"id": "PMID:207772", "title": "Flow microfluorometric analysis of herpesvirus infected BHK-21 and BALB/3T3 cell cultures.", "content": "The interaction of herpes simplex type 1 with two eukaryotic cell lines (BHK-21 and BALB/3T3) was investigated by flow microfluorometric analysis after cell staining with mithramycin. Uninfected, lytically infected and persistently infected cell populations were examined. Viral replication within an infected cell population could be detected via FMF analysis. The low levels of viral replication occurring within persistently infected cell populations were also detectable. A marked degree of correlation was noted between morphological observations of infected cultures and the FMF profiles obtained. The results deomonstrate the great potential of this technique for the early detection and analysis of viral infection.", "contents": "Flow microfluorometric analysis of herpesvirus infected BHK-21 and BALB/3T3 cell cultures. The interaction of herpes simplex type 1 with two eukaryotic cell lines (BHK-21 and BALB/3T3) was investigated by flow microfluorometric analysis after cell staining with mithramycin. Uninfected, lytically infected and persistently infected cell populations were examined. Viral replication within an infected cell population could be detected via FMF analysis. The low levels of viral replication occurring within persistently infected cell populations were also detectable. A marked degree of correlation was noted between morphological observations of infected cultures and the FMF profiles obtained. The results deomonstrate the great potential of this technique for the early detection and analysis of viral infection."}
{"id": "PMID:207773", "title": "Thymopoietin enhances the allogeneic response and cyclic GMP levels of mouse peripheral, thymus-derived lymphocytes.", "content": "The action of the purified thymic factor, thymopoietin, on populations of post-thymic lymphocytes has been studied. Thymopoietin, at concentrations as low as 1.5 ng/ml, uniquely enhanced the proliferative response of peripheral T cells from lymph node and spleen to allogeneic stimulation. Enhancement of the allogeneic response (MLR) was not produced by several polypeptide hormones, including insulin, ACTH, HCG, or Ubiquitin. Treatment of spleen cells with anti-Thy-1 antiserum almost completely abolished the MLR. Thymopoietin's stimulatory effects could not reverse this. Thymopoietin treatment of Thy-1+-enriched spleen cell populations enhanced the MLR even when thymopoietin was removed as early as 2 min after incubation with responding cells. The interaction of thymopoietin with peripheral Thy-1+ cell populations produced a rapid and transient rise in cyclic GMP levels and slightly decreased cyclic AMP levels. These results suggest that thymopoietin interacts with one or more Thy-1+ subpopulations and that this interaction involves early changes in cyclic nucleotide metabolism.", "contents": "Thymopoietin enhances the allogeneic response and cyclic GMP levels of mouse peripheral, thymus-derived lymphocytes. The action of the purified thymic factor, thymopoietin, on populations of post-thymic lymphocytes has been studied. Thymopoietin, at concentrations as low as 1.5 ng/ml, uniquely enhanced the proliferative response of peripheral T cells from lymph node and spleen to allogeneic stimulation. Enhancement of the allogeneic response (MLR) was not produced by several polypeptide hormones, including insulin, ACTH, HCG, or Ubiquitin. Treatment of spleen cells with anti-Thy-1 antiserum almost completely abolished the MLR. Thymopoietin's stimulatory effects could not reverse this. Thymopoietin treatment of Thy-1+-enriched spleen cell populations enhanced the MLR even when thymopoietin was removed as early as 2 min after incubation with responding cells. The interaction of thymopoietin with peripheral Thy-1+ cell populations produced a rapid and transient rise in cyclic GMP levels and slightly decreased cyclic AMP levels. These results suggest that thymopoietin interacts with one or more Thy-1+ subpopulations and that this interaction involves early changes in cyclic nucleotide metabolism."}
{"id": "PMID:207774", "title": "Rous sarcoma virus-transformed avian cells express four different cell surface antigens that are distinguishable by a cell-mediated cytotoxicity-blocking test.", "content": "Japanese quails bearing avian sarcoma virus-induced tumors develop immune spleen cells that are cytotoxic in vitro against virally and chemically transformed cells, as well as against embryonic cells. The cell-mediated cytotoxicity can be blocked by soluble antigens extracted from in vitro cultured cells. The existence of partial as well as total blocking effects in tests with extracts from various transformed and untransformed virus-producing cells makes it possible to distinguish up to four different kinds of antigens expressed on sarcoma virus transformed cells: a) a subgroup-specific determinant of the virus-envelope glycoprotein gp85 (s-gp85) is expressed at the surface of productively infected, tranformed as well as untransformed cells; b) a group-specific determinant of gp85 (g-gp85) that is only expressed on the surface of virus-transformed cells; c) embryonic antigens, also detectable on chemically transformed as well as on primary normal embryonic cells, and finally; d) a sarcoma virus transformation-specific antigen (TSSA) that is not a structural constituent of the virus.", "contents": "Rous sarcoma virus-transformed avian cells express four different cell surface antigens that are distinguishable by a cell-mediated cytotoxicity-blocking test. Japanese quails bearing avian sarcoma virus-induced tumors develop immune spleen cells that are cytotoxic in vitro against virally and chemically transformed cells, as well as against embryonic cells. The cell-mediated cytotoxicity can be blocked by soluble antigens extracted from in vitro cultured cells. The existence of partial as well as total blocking effects in tests with extracts from various transformed and untransformed virus-producing cells makes it possible to distinguish up to four different kinds of antigens expressed on sarcoma virus transformed cells: a) a subgroup-specific determinant of the virus-envelope glycoprotein gp85 (s-gp85) is expressed at the surface of productively infected, tranformed as well as untransformed cells; b) a group-specific determinant of gp85 (g-gp85) that is only expressed on the surface of virus-transformed cells; c) embryonic antigens, also detectable on chemically transformed as well as on primary normal embryonic cells, and finally; d) a sarcoma virus transformation-specific antigen (TSSA) that is not a structural constituent of the virus."}
{"id": "PMID:207775", "title": "Assessment of cell-mediated hypersensitivity against coxsackievirus B3 viral-induced myocarditis utilizing hypertonic salt extracts of cardiac tissue.", "content": "Hypertonic KCl extracts prepared from heart tissues of adolescent CD-1 mice inoculated with coxsackievirus B3 (CVB3) were tested for antigenicity in evaluating cell-mediated sensitivity to CVB3 virus utilizing the agarose droplet cell-migration-inhibition assay. Immune mouse peritoneal exudate cells (IMPEC) from mice immunized against CVB3 virus and Freund's complete adjuvant were specifically inhibited in the cell-migration-inhibition assay with graded doses of KCl-extracted antigen and purified protein derivative (PPD). Unimmunized for \"normal\" mouse peritoneal exudate cells (NMPEC) were not inhibited in the presence of the CVB3 KCl extracts. KCl heart extracts from mice inoculated with a cardiotropic strain of antigenically distinct mengovirus failed to inhibit CVB3 IMPEC, and noncardiac KCl extracts of liver and spleen from CVB3-inoculated mice also failed to inhibit cellular migration of CVB3 IMPEC. Reciprocal specificity experiments utilizing KCl-extracted antigens from mice infected with antigenically distinct cardiotropic mengovirus failed to inhibit cellular migration of IMPEC from mice immunized against the mengovirus. Serum-blocking power experiments indicate the antigenic KCl extracts failed to bind virus-neutralizing antibodies, indicating absence of detectable quantities of virion antigens. The results indicate that inoculation of mice with CVB3 virus results in the appearance of a new antigen(s) in cardiac tissue reacting with CVB3-IMPEC, but not with mengovirus IMPEC.", "contents": "Assessment of cell-mediated hypersensitivity against coxsackievirus B3 viral-induced myocarditis utilizing hypertonic salt extracts of cardiac tissue. Hypertonic KCl extracts prepared from heart tissues of adolescent CD-1 mice inoculated with coxsackievirus B3 (CVB3) were tested for antigenicity in evaluating cell-mediated sensitivity to CVB3 virus utilizing the agarose droplet cell-migration-inhibition assay. Immune mouse peritoneal exudate cells (IMPEC) from mice immunized against CVB3 virus and Freund's complete adjuvant were specifically inhibited in the cell-migration-inhibition assay with graded doses of KCl-extracted antigen and purified protein derivative (PPD). Unimmunized for \"normal\" mouse peritoneal exudate cells (NMPEC) were not inhibited in the presence of the CVB3 KCl extracts. KCl heart extracts from mice inoculated with a cardiotropic strain of antigenically distinct mengovirus failed to inhibit CVB3 IMPEC, and noncardiac KCl extracts of liver and spleen from CVB3-inoculated mice also failed to inhibit cellular migration of CVB3 IMPEC. Reciprocal specificity experiments utilizing KCl-extracted antigens from mice infected with antigenically distinct cardiotropic mengovirus failed to inhibit cellular migration of IMPEC from mice immunized against the mengovirus. Serum-blocking power experiments indicate the antigenic KCl extracts failed to bind virus-neutralizing antibodies, indicating absence of detectable quantities of virion antigens. The results indicate that inoculation of mice with CVB3 virus results in the appearance of a new antigen(s) in cardiac tissue reacting with CVB3-IMPEC, but not with mengovirus IMPEC."}
{"id": "PMID:207776", "title": "Demonstration of a surface antigen on Epstein-Barr virus genome-carrying lymphoid cells: distinction from the virus-determined membrane antigen.", "content": "A surface antigen (SA) was detected on Epstein-Barr virus (EBV)-carrying lymphoid cell lines by indirect membrane immunofluorescence with an antiserum from a rabbit immunized with Raji cells; the antiserum had been extensively absorbed with normal human blood and tonsil cells. The SA was not detected on normal human umbilical cord and adult peripheral blood lymphocytes or EBV-negative cell lines. Incidences of the SA and EBV-determined membrane antigen (MA) on certain EBV-carrying cell lines were not compatible. Antibody against SA was differentially absorbed by the SA-positive MA-negative cell lines whereas MA antibody was absorbed by MA-positive SA-negative cell lines. The results of cross-absorption tests of antiserum against Raji cells or P3HR-1 cells suggested that SA may contain more than one antigenic determinant.", "contents": "Demonstration of a surface antigen on Epstein-Barr virus genome-carrying lymphoid cells: distinction from the virus-determined membrane antigen. A surface antigen (SA) was detected on Epstein-Barr virus (EBV)-carrying lymphoid cell lines by indirect membrane immunofluorescence with an antiserum from a rabbit immunized with Raji cells; the antiserum had been extensively absorbed with normal human blood and tonsil cells. The SA was not detected on normal human umbilical cord and adult peripheral blood lymphocytes or EBV-negative cell lines. Incidences of the SA and EBV-determined membrane antigen (MA) on certain EBV-carrying cell lines were not compatible. Antibody against SA was differentially absorbed by the SA-positive MA-negative cell lines whereas MA antibody was absorbed by MA-positive SA-negative cell lines. The results of cross-absorption tests of antiserum against Raji cells or P3HR-1 cells suggested that SA may contain more than one antigenic determinant."}
{"id": "PMID:207777", "title": "Immunosuppressive activity of antibody directed against endogenous C-type virus interferes with early events of the immune response.", "content": "We have analyzed the effects of an antiserum prepared against BALB/c endogenous xenotropic C-type virus on the humoral immune response of mice. Both in vivo and in vitro, this serum suppresses the response to sheep red blood cells, an effect that can be absorbed out by purified BALB/c xenotropic C-type virus or Friend leukemia virus, but not by Rous sarcoma virus. The serum produces its maximum effect when administered together with or before the antigen, but not 24 hr later. This suggests that it acts on an early event of the immune response. Evidence is presented to show that the critical viral antigen is expressed before the spleen cells are experimentally stimulated by antigen. The same immunosuppressive effect was observed in a variety of mouse strains, including the high-leukemia incidence AKR strain and virus-free 129/J mice, indicating that it is independent of the expression of endogenous virus. The finding that a viral antigen is involved in the transition from a resting to a dividing lymphocyte is discussed with respect to viral involvement in leukemia.", "contents": "Immunosuppressive activity of antibody directed against endogenous C-type virus interferes with early events of the immune response. We have analyzed the effects of an antiserum prepared against BALB/c endogenous xenotropic C-type virus on the humoral immune response of mice. Both in vivo and in vitro, this serum suppresses the response to sheep red blood cells, an effect that can be absorbed out by purified BALB/c xenotropic C-type virus or Friend leukemia virus, but not by Rous sarcoma virus. The serum produces its maximum effect when administered together with or before the antigen, but not 24 hr later. This suggests that it acts on an early event of the immune response. Evidence is presented to show that the critical viral antigen is expressed before the spleen cells are experimentally stimulated by antigen. The same immunosuppressive effect was observed in a variety of mouse strains, including the high-leukemia incidence AKR strain and virus-free 129/J mice, indicating that it is independent of the expression of endogenous virus. The finding that a viral antigen is involved in the transition from a resting to a dividing lymphocyte is discussed with respect to viral involvement in leukemia."}
{"id": "PMID:207779", "title": "Spin membrane immunoassay: simplicity and specificity.", "content": "The many disadvantages of radioimmunoassay (RIA) have stimulated attempts to develop non-radioactive assays. These include spin immunoassay (SIA), which is simple, specific, and requires no separation procedures but is much less sensitive than RIA. The membrane immunoassay (MIA) described here is more sensitive than the SIA. Serum is prepared as for RIA. The MIA employs liposomes sensitized with epsilon-dinitrophenylated aminocaproyl phosphatidylethanolamine. It records liposome lysis induced by specific anti-Dnp antibodies, and complement which is monitored by the release of trapped spin labels (N-(2,2,6,6-tetramethylpiperidinyl-1-oxyl)-choline chloride). The sensitized liposomes are stable and give reproducible results for up to 4 weeks. The system's sensitivity is limited by the antibody's affinity (Ka approximately 10(8) M-1) rather than the sensitivity of the electron spin resonance spectrometer (approximately 1 X 10(-7) M). The inhibition of liposome lysis is hapten specific: (epsilon-Dnp-aminocaproic acid,epsilon-Dnp-lysine) greater than alpha-Dnp-glycine; o-nitroaniline and epsilon-dansyl-lysine are ineffective. Inhibition is quantitative without augmentation.", "contents": "Spin membrane immunoassay: simplicity and specificity. The many disadvantages of radioimmunoassay (RIA) have stimulated attempts to develop non-radioactive assays. These include spin immunoassay (SIA), which is simple, specific, and requires no separation procedures but is much less sensitive than RIA. The membrane immunoassay (MIA) described here is more sensitive than the SIA. Serum is prepared as for RIA. The MIA employs liposomes sensitized with epsilon-dinitrophenylated aminocaproyl phosphatidylethanolamine. It records liposome lysis induced by specific anti-Dnp antibodies, and complement which is monitored by the release of trapped spin labels (N-(2,2,6,6-tetramethylpiperidinyl-1-oxyl)-choline chloride). The sensitized liposomes are stable and give reproducible results for up to 4 weeks. The system's sensitivity is limited by the antibody's affinity (Ka approximately 10(8) M-1) rather than the sensitivity of the electron spin resonance spectrometer (approximately 1 X 10(-7) M). The inhibition of liposome lysis is hapten specific: (epsilon-Dnp-aminocaproic acid,epsilon-Dnp-lysine) greater than alpha-Dnp-glycine; o-nitroaniline and epsilon-dansyl-lysine are ineffective. Inhibition is quantitative without augmentation."}
{"id": "PMID:207780", "title": "Immunoabsorbents prepared from cell membrane antigens: efficiency of incorporation and shedding of protein during use.", "content": "Immunoabsorbents for the removal of antibodies against cell membrane antigens have been prepared by a variety of techniques in common use. Cells were surface-labelled by lactoperoxidase-catalysed radioiodination, and the different immunoabsorbent preparations were compared in terms of efficiency of incorporation and shedding of membrane material during use. Whole cells, either unfixed or fixed with glutaraldehyde, shed substantial amounts of material during absorption. Detergent extracts of surface-labelled cells were coupled covalently to agarose beads by cyanogen bromide activation, periodate oxidation, or epoxy activation of the gel. Although these immunoadsorbents were much more stable than whole cells, shedding could not be eliminated entirely. Minimal shedding was achieved using freshly washed epoxy-based immunoadsorbents. The possible consequences of shed protein in immunoabsorbed sera are emphasised.", "contents": "Immunoabsorbents prepared from cell membrane antigens: efficiency of incorporation and shedding of protein during use. Immunoabsorbents for the removal of antibodies against cell membrane antigens have been prepared by a variety of techniques in common use. Cells were surface-labelled by lactoperoxidase-catalysed radioiodination, and the different immunoabsorbent preparations were compared in terms of efficiency of incorporation and shedding of membrane material during use. Whole cells, either unfixed or fixed with glutaraldehyde, shed substantial amounts of material during absorption. Detergent extracts of surface-labelled cells were coupled covalently to agarose beads by cyanogen bromide activation, periodate oxidation, or epoxy activation of the gel. Although these immunoadsorbents were much more stable than whole cells, shedding could not be eliminated entirely. Minimal shedding was achieved using freshly washed epoxy-based immunoadsorbents. The possible consequences of shed protein in immunoabsorbed sera are emphasised."}
{"id": "PMID:207781", "title": "Partial purification and characterization of the inherited Hl 1 and R 67 antigens of rabbit serum high density lipoprotein.", "content": "Purification and characterization of the Hl 1 antigen revealed a polypeptide with molecular weight of 20,000 by gel filtration. The peptide contained 20% neutral sugar and 4.5% neuraminic acid. Amino acid analysis as well as the N-terminal sequence for thirteen amino acid residues and three C-terminal amino acids were determined. Difference index analysis gave an indication that the Hl 1 polypeptide is unique. Purification of R 67 antigen did not give a pure polypeptide in sufficient amount to do chemical analysis. A crude fraction of R 67 antigen had three bands on SDS-PAGE, all with R 67 antigenic activity. The crude fraction contained 10% neutral sugar and 3.5% neuraminic acid. No N- or C-terminal amino acids could be determined for the crude fraction of R 67 antigen.", "contents": "Partial purification and characterization of the inherited Hl 1 and R 67 antigens of rabbit serum high density lipoprotein. Purification and characterization of the Hl 1 antigen revealed a polypeptide with molecular weight of 20,000 by gel filtration. The peptide contained 20% neutral sugar and 4.5% neuraminic acid. Amino acid analysis as well as the N-terminal sequence for thirteen amino acid residues and three C-terminal amino acids were determined. Difference index analysis gave an indication that the Hl 1 polypeptide is unique. Purification of R 67 antigen did not give a pure polypeptide in sufficient amount to do chemical analysis. A crude fraction of R 67 antigen had three bands on SDS-PAGE, all with R 67 antigenic activity. The crude fraction contained 10% neutral sugar and 3.5% neuraminic acid. No N- or C-terminal amino acids could be determined for the crude fraction of R 67 antigen."}
{"id": "PMID:207782", "title": "Selective impairment of lymphocyte reactivity to varicella-zoster virus antigen among untreated patients with lymphoma.", "content": "Herpes zoster is a frequent complication of lymphoreticular malignancy. In this study two assays of in vitro cellular immune response to varicella-zoster virus (VZV) antigen, lymphocyte transformation and interferon production, were performed in normal subjects with recent and remote VZV infection. The responses of patients with lymphoma were measured before treatment and during long-term remission and then compared with those of normal subjects. Despite levels of antibody to VZV that were equivalent to those in normal subjects, 44% of the untreated lymphoma patients showed a lower transformation response to VZV antigen than the normal patients. Production of interferon in response to VZV antigen was absent in 32% of the untreated patients. In contrast, lymphocyte responses in untreated patients to herpes simplex virus antigen were within the range observed in a normal population. Interferon production by lymphocytes in response to cytomegalovirus antigen was also lower among untreated lymphoma patients than among normal patients, but lymphocyte transformation was not. Twenty-two percent of lymphoma patients in long-term remission continued to have diminished cellular immune responses to VZV antigen. Observations in these patient populations and in normal subjects with acute herpes zoster suggest that deficiencies in in vitro lymphocyte responses may correlate with increased susceptibility to clinical infection with VZV.", "contents": "Selective impairment of lymphocyte reactivity to varicella-zoster virus antigen among untreated patients with lymphoma. Herpes zoster is a frequent complication of lymphoreticular malignancy. In this study two assays of in vitro cellular immune response to varicella-zoster virus (VZV) antigen, lymphocyte transformation and interferon production, were performed in normal subjects with recent and remote VZV infection. The responses of patients with lymphoma were measured before treatment and during long-term remission and then compared with those of normal subjects. Despite levels of antibody to VZV that were equivalent to those in normal subjects, 44% of the untreated lymphoma patients showed a lower transformation response to VZV antigen than the normal patients. Production of interferon in response to VZV antigen was absent in 32% of the untreated patients. In contrast, lymphocyte responses in untreated patients to herpes simplex virus antigen were within the range observed in a normal population. Interferon production by lymphocytes in response to cytomegalovirus antigen was also lower among untreated lymphoma patients than among normal patients, but lymphocyte transformation was not. Twenty-two percent of lymphoma patients in long-term remission continued to have diminished cellular immune responses to VZV antigen. Observations in these patient populations and in normal subjects with acute herpes zoster suggest that deficiencies in in vitro lymphocyte responses may correlate with increased susceptibility to clinical infection with VZV."}
{"id": "PMID:207783", "title": "Cell-mediated immunity of cytomegalovirus infection in normal subjects and cardiac transplant patients.", "content": "Two assays of cell-mediated immunity, lymphocyte transformation and interferon production, were adapted to test for specific immunity to cytomegalovirus (CMV). Normal individuals seropositive for CMV had a mean transformation index of 7.9 in response to antigen of the Davis strain of CMV, whereas all of 14 seronegative normal individuals had transformation indexes of less than or equal to 3.0. Interferon production in seropositive and seronegative individuals was not statistically different. One to two months after CMV mononucleosis (after the termination of viruria), normal individuals had increased transformation indexes. Recipients of cardiac transplants within six months after transplant had normal levels of antibody to CMV; lymphocyte transformation and interferon production in these subjects were markedly decreased and returned to normal by three years and between one and three years after transplant, respectively. A syndrome of unexplained fever, hepatitis, pneumonitis, leukopenia, and atypical lymphocytes was common in a group of recipients with primary CMV infection. Shedding of virus was frequent in these symptomatic patients and in patients with repeat infection during the first three years after transplant. These assays appear to identify periods of immune deficits correlating with increased incidence of infection with CMV.", "contents": "Cell-mediated immunity of cytomegalovirus infection in normal subjects and cardiac transplant patients. Two assays of cell-mediated immunity, lymphocyte transformation and interferon production, were adapted to test for specific immunity to cytomegalovirus (CMV). Normal individuals seropositive for CMV had a mean transformation index of 7.9 in response to antigen of the Davis strain of CMV, whereas all of 14 seronegative normal individuals had transformation indexes of less than or equal to 3.0. Interferon production in seropositive and seronegative individuals was not statistically different. One to two months after CMV mononucleosis (after the termination of viruria), normal individuals had increased transformation indexes. Recipients of cardiac transplants within six months after transplant had normal levels of antibody to CMV; lymphocyte transformation and interferon production in these subjects were markedly decreased and returned to normal by three years and between one and three years after transplant, respectively. A syndrome of unexplained fever, hepatitis, pneumonitis, leukopenia, and atypical lymphocytes was common in a group of recipients with primary CMV infection. Shedding of virus was frequent in these symptomatic patients and in patients with repeat infection during the first three years after transplant. These assays appear to identify periods of immune deficits correlating with increased incidence of infection with CMV."}
{"id": "PMID:207784", "title": "Productive infection with cytomegalovirus and herpes simplex virus in renal transplant recipients: role of source of kidney.", "content": "Forty patients were prospectively studied for infection with cytomegalovirus (CMV) and herpes simplex virus (HSV) after renal transplantation. Although 85% had antibody to CMV and 95% had antibody to HSV prior to transplantation, excretion of CMV was found in 92.5%, usually as viruria, and HSV was recovered from 70%, most often from the oropharynx. Shedding of HSV reached a peak within the first month after transplantation when immunosuppression was most intense and then rapidly declined. In contrast, excretion of CMV was found in a greater proportion of patients during each interval up to about six months after transplantation and subsequently persisted in the majority of patients. Both serologic responses and viral isolation rates indicated more rapid activation of CMV but not of HSV in recipients of kidneys from cadavers than in patients who received kidneys from living related donors. At 60 days after transplantation, 76% of the recipients of kidneys from cadavers and only 33% of the recipients of kidneys from living, related donors had shed CMV (P = 0.003). These differences could not be accounted for by immunosuppressive treatment. Excretion of HSV was clearly associated with the time of most intense immunosuppression, but the major factor in initiation and maintenance of productive infection with CMV appeared to be the host vs. graft reaction.", "contents": "Productive infection with cytomegalovirus and herpes simplex virus in renal transplant recipients: role of source of kidney. Forty patients were prospectively studied for infection with cytomegalovirus (CMV) and herpes simplex virus (HSV) after renal transplantation. Although 85% had antibody to CMV and 95% had antibody to HSV prior to transplantation, excretion of CMV was found in 92.5%, usually as viruria, and HSV was recovered from 70%, most often from the oropharynx. Shedding of HSV reached a peak within the first month after transplantation when immunosuppression was most intense and then rapidly declined. In contrast, excretion of CMV was found in a greater proportion of patients during each interval up to about six months after transplantation and subsequently persisted in the majority of patients. Both serologic responses and viral isolation rates indicated more rapid activation of CMV but not of HSV in recipients of kidneys from cadavers than in patients who received kidneys from living related donors. At 60 days after transplantation, 76% of the recipients of kidneys from cadavers and only 33% of the recipients of kidneys from living, related donors had shed CMV (P = 0.003). These differences could not be accounted for by immunosuppressive treatment. Excretion of HSV was clearly associated with the time of most intense immunosuppression, but the major factor in initiation and maintenance of productive infection with CMV appeared to be the host vs. graft reaction."}
{"id": "PMID:207785", "title": "Perinatal cytomegalovirus infection: influence of placentally transferred maternal antibody.", "content": "The kinetics of the response to passively transferred maternal neutralizing antibody were studied for determination of whether this antibody offered protection against primary cytomegalovirus (CMV) infection in the offspring. Antibody response was determined in 17 infants infected in the immediate perinatal period and in 18 appropriate control subjects. Levels of neutralizing antibody in serum obtained at birth and at one month of age were similar in infected and in exposed, uninfected neonates. In addition, the quantity of neutralizing antibody did not influence the time of onset of viruria. Clearly, passive humoral immunity failed to prevent naturally acquired primary CMV infection in a significant number of young infants exposed to virus during and shortly after delivery.", "contents": "Perinatal cytomegalovirus infection: influence of placentally transferred maternal antibody. The kinetics of the response to passively transferred maternal neutralizing antibody were studied for determination of whether this antibody offered protection against primary cytomegalovirus (CMV) infection in the offspring. Antibody response was determined in 17 infants infected in the immediate perinatal period and in 18 appropriate control subjects. Levels of neutralizing antibody in serum obtained at birth and at one month of age were similar in infected and in exposed, uninfected neonates. In addition, the quantity of neutralizing antibody did not influence the time of onset of viruria. Clearly, passive humoral immunity failed to prevent naturally acquired primary CMV infection in a significant number of young infants exposed to virus during and shortly after delivery."}
{"id": "PMID:207786", "title": "Salivary neutralizing activity against herpes simplex virus type 1.", "content": "Samples of saliva collected from 40 patients, of whom 16 had a previous clinical history of herpes simplex virus type 1 (HSV-1) infection, were concentrated and sterilized. Salivary neutralizing activity, as measured by a plaque-reduction method, was found in 62% of those patients with a history of oral lesions. Studies with antisera to human immunoglobulin indicated that the IgG class of immunoglobulin was a major HSV-1-neutralizing component of both saliva and serum.", "contents": "Salivary neutralizing activity against herpes simplex virus type 1. Samples of saliva collected from 40 patients, of whom 16 had a previous clinical history of herpes simplex virus type 1 (HSV-1) infection, were concentrated and sterilized. Salivary neutralizing activity, as measured by a plaque-reduction method, was found in 62% of those patients with a history of oral lesions. Studies with antisera to human immunoglobulin indicated that the IgG class of immunoglobulin was a major HSV-1-neutralizing component of both saliva and serum."}
{"id": "PMID:207787", "title": "Splenic necrosis in mice infected with cytomegalovirus.", "content": "Necrosis of the spleen is seen in mice of certain strains after injection of large doses of murine cytomegalovirus. Necrosis begins in perifollicular areas containing infected cells which do not appear to be macrophages, and in severe cases the entire spleen is involved. Necrosis is first visible three days after infection and is not prevented by treatment of mice with corticosteroids, cyclophosphamide, or theta antiserum. There is a striking loss of nucleated cells from the spleen at two to four days after infection, in the absence of splenic necrosis. The pathogenesis of splenic necrosis, which is seen also in certain other viral infections, remains unexplained.", "contents": "Splenic necrosis in mice infected with cytomegalovirus. Necrosis of the spleen is seen in mice of certain strains after injection of large doses of murine cytomegalovirus. Necrosis begins in perifollicular areas containing infected cells which do not appear to be macrophages, and in severe cases the entire spleen is involved. Necrosis is first visible three days after infection and is not prevented by treatment of mice with corticosteroids, cyclophosphamide, or theta antiserum. There is a striking loss of nucleated cells from the spleen at two to four days after infection, in the absence of splenic necrosis. The pathogenesis of splenic necrosis, which is seen also in certain other viral infections, remains unexplained."}
{"id": "PMID:207788", "title": "A practical method for preparation of varicella-zoster immune globulin.", "content": "Outdated blood from blood banks in Massachusetts was screened for complement-fixing antibody to varicella-zoster virus (VZV). Approximately 15% of the plasma units had a titer greater than or equal to 16, and one-half of these had a titer of greater than or equal to 32. Plasma units with titers of CF antibody to VZV of greater than or equal to 16 were pooled. This pool had a CF antibody titer of 32 and a titer of fluorescent antibody of 64. Varicella-zoster immune globulin was prepared from the selected plasma pool by alcohol fractionation and analyzed for VZV-specific antibody. Varicella-zoster immune globulin had a fluorescent antibody titer of 2,048 and a neutralizing antibody titer of 1,024. This antibody concentration is equivalent to that in preparations of zoster immune globulin made from plasma of donors recovering from recent VZV infection.", "contents": "A practical method for preparation of varicella-zoster immune globulin. Outdated blood from blood banks in Massachusetts was screened for complement-fixing antibody to varicella-zoster virus (VZV). Approximately 15% of the plasma units had a titer greater than or equal to 16, and one-half of these had a titer of greater than or equal to 32. Plasma units with titers of CF antibody to VZV of greater than or equal to 16 were pooled. This pool had a CF antibody titer of 32 and a titer of fluorescent antibody of 64. Varicella-zoster immune globulin was prepared from the selected plasma pool by alcohol fractionation and analyzed for VZV-specific antibody. Varicella-zoster immune globulin had a fluorescent antibody titer of 2,048 and a neutralizing antibody titer of 1,024. This antibody concentration is equivalent to that in preparations of zoster immune globulin made from plasma of donors recovering from recent VZV infection."}
{"id": "PMID:207790", "title": "Determinants of measles virus (hamster neurotropic strain) replication in mouse brain.", "content": "In newborn mice the hamster neurotropic strain of measles virus produces a severe meningoencephalitis with readily recoverable virus, while in weanling mice a fatal encephalopathy is produced with scant histopathology and no viral infectivity in brain homogenates. In this study various host factors that may change with maturation and determine the restriction of viral expression were investigated, including immune response, interferon production, host temperature, and the possible role of proteases. None of these factors appeared to be responsible for host restriction of viral expression. Recovery of virus from brains of weanling mice was not significantly enhanced by cocultivation with Vero cells, complementation with temperature-sensitive mutants, or phenotypic mixing with the Edmonston strain of measles virus. These data, combined with our previous observations of production of viral proteins including nucleocapsid proteins without development of recognizable nucleocapsids in neurons of weanling mice, suggest that with maturation the neural cells fail to replicate sufficient amounts of encapsidated viral ribonucleic acid.", "contents": "Determinants of measles virus (hamster neurotropic strain) replication in mouse brain. In newborn mice the hamster neurotropic strain of measles virus produces a severe meningoencephalitis with readily recoverable virus, while in weanling mice a fatal encephalopathy is produced with scant histopathology and no viral infectivity in brain homogenates. In this study various host factors that may change with maturation and determine the restriction of viral expression were investigated, including immune response, interferon production, host temperature, and the possible role of proteases. None of these factors appeared to be responsible for host restriction of viral expression. Recovery of virus from brains of weanling mice was not significantly enhanced by cocultivation with Vero cells, complementation with temperature-sensitive mutants, or phenotypic mixing with the Edmonston strain of measles virus. These data, combined with our previous observations of production of viral proteins including nucleocapsid proteins without development of recognizable nucleocapsids in neurons of weanling mice, suggest that with maturation the neural cells fail to replicate sufficient amounts of encapsidated viral ribonucleic acid."}
{"id": "PMID:207792", "title": "Synergistic infection with murine cytomegalovirus and Pseudomonas aeruginosa in mice.", "content": "A previous report from this laboratory demonstrated that mice infected intraperitoneally with a 0--20% lethal inoculum of murine cytomegalovirus (CMV) exhibited markedly enhanced mortality rates (90%--100%) within 48 hr after an intravenous injection of a 0--20% lethal inoculum of Pseudomonas aeruginosa. The current study demonstrated that mice infected with murine CMV alone had high titers of virus in multiple organs over a 20-day period, whereas mice injected with P. aeruginosa alone had a self-limited infection confined to the kidney. In the combined murine CMV-P. aeruginosa infection, titers of virus in tissues were changed very little. In contrast, P. aeruginosa was recovered in high concentrations from multiple organs, a finding which demonstrated a progressive systemic infection closely resembling that produced by a 100% lethal inoculum of P. aeruginosa alone in normal mice. An increased mortality rate due to P. aeruginosa in murine CMV-infected mice was dependent on inoculation of live bacteria and could not be explained by enhanced susceptibility to endotoxin. These results indicate that murine CMF markedly enhanced the suceptibility of mice to infection with P. aeruginosa and suggest that the virus altered mechanisms of host resistance important in recovery from bacterial infections.", "contents": "Synergistic infection with murine cytomegalovirus and Pseudomonas aeruginosa in mice. A previous report from this laboratory demonstrated that mice infected intraperitoneally with a 0--20% lethal inoculum of murine cytomegalovirus (CMV) exhibited markedly enhanced mortality rates (90%--100%) within 48 hr after an intravenous injection of a 0--20% lethal inoculum of Pseudomonas aeruginosa. The current study demonstrated that mice infected with murine CMV alone had high titers of virus in multiple organs over a 20-day period, whereas mice injected with P. aeruginosa alone had a self-limited infection confined to the kidney. In the combined murine CMV-P. aeruginosa infection, titers of virus in tissues were changed very little. In contrast, P. aeruginosa was recovered in high concentrations from multiple organs, a finding which demonstrated a progressive systemic infection closely resembling that produced by a 100% lethal inoculum of P. aeruginosa alone in normal mice. An increased mortality rate due to P. aeruginosa in murine CMV-infected mice was dependent on inoculation of live bacteria and could not be explained by enhanced susceptibility to endotoxin. These results indicate that murine CMF markedly enhanced the suceptibility of mice to infection with P. aeruginosa and suggest that the virus altered mechanisms of host resistance important in recovery from bacterial infections."}
{"id": "PMID:207798", "title": "Granular cell myoblastoma of the larynx.", "content": "Two cases of granular cell myoblastoma of the larynx are presented. In the first case the tumour was excised by laryngofissure, and in the second case by microlaryngoscopy. Based on this experience a review of this interesting tumour is made, and emphasis is given to the fact that this neoplasm may be mistaken for squamous cell carcinoma.", "contents": "Granular cell myoblastoma of the larynx. Two cases of granular cell myoblastoma of the larynx are presented. In the first case the tumour was excised by laryngofissure, and in the second case by microlaryngoscopy. Based on this experience a review of this interesting tumour is made, and emphasis is given to the fact that this neoplasm may be mistaken for squamous cell carcinoma."}
{"id": "PMID:207800", "title": "Effects of dietary fat composition on the Ehrlich ascites tumor fluid lipoproteins.", "content": "Mice bearing the Ehrlich ascites tumor were fed diets rich in either coconut oil or sunflower oil. From 20 to 40% less lipid was present in the ascites tumor fluid when the mice were fed the sunflower oil diet. This was associated with a reduction in the amount of very low density lipoproteins (VLDL) and high density lipoproteins (HDL), the main lipoprotein fractions present in the ascites tumor fluid. The VLDL from the mice fed sunflower oil contained more cholesteryl esters and a lower free to esterified cholesterol ratio than those from the mice fed coconut oil. Very little change occurred in the composition of the HDL. All of the lipids contained in both lipoprotein fractions exhibited appreciable differences in fatty acid composition. Much more monoenoic and less polyenoic fatty acid were present in the lipids from the mice fed the coconut oil diet, but no appreciable change in saturated fatty acid content occurred. Similar changes in fatty acid composition were observed in the blood plasma of the tumor-bearing mice. There was no qualitative difference in the apolipoprotein patterns of either the ascites fluid VLDL or HDL. Pyrene fluorescence studies indicated that the fluidity of the VLDL was increased when the mice were fed the sunflower oil diets. No difference in HDL fluidity, however, was observed by this technique. These results indicate that the amount, composition, and physical properties of certain of the lipoproteins contained in the ascites tumor fluid can be modified by changing the composition of the dietary fat fed to mice bearing the Ehrlich ascites tumor.", "contents": "Effects of dietary fat composition on the Ehrlich ascites tumor fluid lipoproteins. Mice bearing the Ehrlich ascites tumor were fed diets rich in either coconut oil or sunflower oil. From 20 to 40% less lipid was present in the ascites tumor fluid when the mice were fed the sunflower oil diet. This was associated with a reduction in the amount of very low density lipoproteins (VLDL) and high density lipoproteins (HDL), the main lipoprotein fractions present in the ascites tumor fluid. The VLDL from the mice fed sunflower oil contained more cholesteryl esters and a lower free to esterified cholesterol ratio than those from the mice fed coconut oil. Very little change occurred in the composition of the HDL. All of the lipids contained in both lipoprotein fractions exhibited appreciable differences in fatty acid composition. Much more monoenoic and less polyenoic fatty acid were present in the lipids from the mice fed the coconut oil diet, but no appreciable change in saturated fatty acid content occurred. Similar changes in fatty acid composition were observed in the blood plasma of the tumor-bearing mice. There was no qualitative difference in the apolipoprotein patterns of either the ascites fluid VLDL or HDL. Pyrene fluorescence studies indicated that the fluidity of the VLDL was increased when the mice were fed the sunflower oil diets. No difference in HDL fluidity, however, was observed by this technique. These results indicate that the amount, composition, and physical properties of certain of the lipoproteins contained in the ascites tumor fluid can be modified by changing the composition of the dietary fat fed to mice bearing the Ehrlich ascites tumor."}
{"id": "PMID:207801", "title": "Pulmonary surfactant synthesis. A highly active microsomal phosphatidate phosphohydrolase in the lung.", "content": "Lung cell-free homogenate, which contains about twice the units of phosphatidate phosphohydrolase per mg of protein compared to liver, was fractionated by differential centrifugation and the fractions were assayed for phosphatidate phosphohydrolase and marker enzymes of endoplasmic reticulum, mitochondria, and lysosomes. Over 60% of the lung phosphatidate phosphohydrolase was associated with the endoplasmic reticulum, compared to 50% of the total liver enzyme. Thus a major portion  of the more active lung enzyme is potentially involved in lipid biosynthesis by the endoplasmic reticulum. Less than 0.2% of the total lung enzyme was found in a lamellar body fraction, consistent with previous findings. The lung microsomal phosphohydrolase was specific for lipid substrates, showing equal activity towards phosphatidic acid or lysophosphatidic acid and relatively low activities towards glycerophosphates. It had a neutral pH optimum, similar to the liver enzyme, but differed somewhat in its relative activity at extremes of pH. Stability at 65 degrees C was greater for the lung enzyme. Fluroide inhibited lung (or liver) microsomal phosphatidate phosphohydrolase, while tartrate, MgCl2, or EDTA had no effect. The presence of a high activity of phosphatidate phosphohydrolase in lung endoplasmic reticulum is consistent with the rapid synthesis of pulmonary surfactant phosphatidylcholine.", "contents": "Pulmonary surfactant synthesis. A highly active microsomal phosphatidate phosphohydrolase in the lung. Lung cell-free homogenate, which contains about twice the units of phosphatidate phosphohydrolase per mg of protein compared to liver, was fractionated by differential centrifugation and the fractions were assayed for phosphatidate phosphohydrolase and marker enzymes of endoplasmic reticulum, mitochondria, and lysosomes. Over 60% of the lung phosphatidate phosphohydrolase was associated with the endoplasmic reticulum, compared to 50% of the total liver enzyme. Thus a major portion  of the more active lung enzyme is potentially involved in lipid biosynthesis by the endoplasmic reticulum. Less than 0.2% of the total lung enzyme was found in a lamellar body fraction, consistent with previous findings. The lung microsomal phosphohydrolase was specific for lipid substrates, showing equal activity towards phosphatidic acid or lysophosphatidic acid and relatively low activities towards glycerophosphates. It had a neutral pH optimum, similar to the liver enzyme, but differed somewhat in its relative activity at extremes of pH. Stability at 65 degrees C was greater for the lung enzyme. Fluroide inhibited lung (or liver) microsomal phosphatidate phosphohydrolase, while tartrate, MgCl2, or EDTA had no effect. The presence of a high activity of phosphatidate phosphohydrolase in lung endoplasmic reticulum is consistent with the rapid synthesis of pulmonary surfactant phosphatidylcholine."}
{"id": "PMID:207802", "title": "Proteolytic digestion in the elucidation of the structure of low density lipoprotein.", "content": "The apoprotein (apoB) of low density lipoprotein (LDL) is reported to be a large polypeptide, and it is proposed that there are two similar-sized subunit proteins in LDL (Smith, Dawson, and Tanford. 1972. J. Biol. Chem. 247: 3376-3381.). When apoB is isolated under conditions that minimize artifactual proteolysis, only a single, large molecular weight protein appears on polyacrylamide gel electrophoresis in SDS. To investigate the organization of apoB as it exists within native LDL, limited proteolysis with trypsin has been used as a structural probe. Tryptic digestion for 1 hr at pH 7.6 with enzyme-to-protein ratios of 1:100 and 1:5 results in the liberation of approximately 10% and 30% of apoB as smaller, water-soluble peptides. These peptides may be separated from the partially digested but still intact tryptic core (T-core) of the lipoprotein by chromatography on Sephadex G-75. Repeatedly, the 1:5 T-core of native LDL is found to contain a family of polypeptides of 14,000-100,000 molecular weight. Although they have lost significant quantities of apoprotein, these T-cores sustain an appearance of homogeneity, as studied by analytical ultracentrifugation. Their measured molecular weights do not differ appreciably from those of the native LDL, and the carbohydrate content of the 1:5 tryptic T-core of LDL is similar to that of the native LDL. In normolipemic individuals, LDL generally exists in a monodisperse state, but, in different individuals, monodisperse LDL may range in molecular weight from 2.4 to 3.9 x 10(6). Limited tryptic digestions were used to probe the organization of apoB in these different molecular weight LDL. As assayed by SDS-acrylamide gel electrophoresis of the larger polypeptides and fingerprinting of the smaller released peptides, those regions of LDL exposed to trypsin digestion are identical in monodisperse LDL of 2.5 and 3.4 x 10(6) molecular weight. Thus, the different quantities of lipid bound in these various LDL must interact with apoB so that the same regions of the apoprotein are exposed to the action of trypsin in these different molecular weight lipoproteins.", "contents": "Proteolytic digestion in the elucidation of the structure of low density lipoprotein. The apoprotein (apoB) of low density lipoprotein (LDL) is reported to be a large polypeptide, and it is proposed that there are two similar-sized subunit proteins in LDL (Smith, Dawson, and Tanford. 1972. J. Biol. Chem. 247: 3376-3381.). When apoB is isolated under conditions that minimize artifactual proteolysis, only a single, large molecular weight protein appears on polyacrylamide gel electrophoresis in SDS. To investigate the organization of apoB as it exists within native LDL, limited proteolysis with trypsin has been used as a structural probe. Tryptic digestion for 1 hr at pH 7.6 with enzyme-to-protein ratios of 1:100 and 1:5 results in the liberation of approximately 10% and 30% of apoB as smaller, water-soluble peptides. These peptides may be separated from the partially digested but still intact tryptic core (T-core) of the lipoprotein by chromatography on Sephadex G-75. Repeatedly, the 1:5 T-core of native LDL is found to contain a family of polypeptides of 14,000-100,000 molecular weight. Although they have lost significant quantities of apoprotein, these T-cores sustain an appearance of homogeneity, as studied by analytical ultracentrifugation. Their measured molecular weights do not differ appreciably from those of the native LDL, and the carbohydrate content of the 1:5 tryptic T-core of LDL is similar to that of the native LDL. In normolipemic individuals, LDL generally exists in a monodisperse state, but, in different individuals, monodisperse LDL may range in molecular weight from 2.4 to 3.9 x 10(6). Limited tryptic digestions were used to probe the organization of apoB in these different molecular weight LDL. As assayed by SDS-acrylamide gel electrophoresis of the larger polypeptides and fingerprinting of the smaller released peptides, those regions of LDL exposed to trypsin digestion are identical in monodisperse LDL of 2.5 and 3.4 x 10(6) molecular weight. Thus, the different quantities of lipid bound in these various LDL must interact with apoB so that the same regions of the apoprotein are exposed to the action of trypsin in these different molecular weight lipoproteins."}
{"id": "PMID:207803", "title": "A convenient synthesis of 3-keto bile acids by selective oxidation of bile acids with silver carbonate-Celite.", "content": "A number of 3-keto bile acids were synthesized by the selective oxidation of bile acid methyl esters with silver carbonate-Celite in refluxing toluene. The pure 3-keto bile acids were isolated simply by filtering the reaction mixture and concentrating the filtrate. The relation of the bile acid structure to the oxidation rate is also discussed.", "contents": "A convenient synthesis of 3-keto bile acids by selective oxidation of bile acids with silver carbonate-Celite. A number of 3-keto bile acids were synthesized by the selective oxidation of bile acid methyl esters with silver carbonate-Celite in refluxing toluene. The pure 3-keto bile acids were isolated simply by filtering the reaction mixture and concentrating the filtrate. The relation of the bile acid structure to the oxidation rate is also discussed."}
{"id": "PMID:207804", "title": "A spectrophotometric method for the assay of cytidine 5'-diphospho-1,2-diacyl-sn-glycerol-dependent enzymes of phospholipid metabolism.", "content": "Cytidine 5'-diphospho-1,2-diacyl-sn-glycerol (CDP-diglyceride) hydrolase, CDP-diglyceride:L-serine O-phosphatidyltransferase, and CDP-diglyceride:sn-glycero-3-phosphate phosphatidyltransferase all release CMP from their liponucleotide substrate, CDP-diglyceride. We have developed a spectrophotometric assay for these enzymes using CMP kinase, pyruvate kinase, and lactate dehydrogenase to couple the release of CMP with the oxidation of NADH. The assay for each of the phospholipid-dependent enzymes was found to be linear both with time and with enzyme concentration. The assay should prove useful for continuous monitoring of enzymatic activity, determination of initial rates of reaction, and detailed kinetic analysis of these enzymes. Since several enzymes and substrates are used in the coupled assay system, the method is limited to analysis of partially purified preparations lacking competing activities.", "contents": "A spectrophotometric method for the assay of cytidine 5'-diphospho-1,2-diacyl-sn-glycerol-dependent enzymes of phospholipid metabolism. Cytidine 5'-diphospho-1,2-diacyl-sn-glycerol (CDP-diglyceride) hydrolase, CDP-diglyceride:L-serine O-phosphatidyltransferase, and CDP-diglyceride:sn-glycero-3-phosphate phosphatidyltransferase all release CMP from their liponucleotide substrate, CDP-diglyceride. We have developed a spectrophotometric assay for these enzymes using CMP kinase, pyruvate kinase, and lactate dehydrogenase to couple the release of CMP with the oxidation of NADH. The assay for each of the phospholipid-dependent enzymes was found to be linear both with time and with enzyme concentration. The assay should prove useful for continuous monitoring of enzymatic activity, determination of initial rates of reaction, and detailed kinetic analysis of these enzymes. Since several enzymes and substrates are used in the coupled assay system, the method is limited to analysis of partially purified preparations lacking competing activities."}
{"id": "PMID:207816", "title": "Calcium and cyclic nucleotide regulation in incubated mouse retinas.", "content": "When retinas from dark-adapted C57BL/6 mice were incubated in the dark for 5 min at 37 degrees C in Earle's medium, they contained 80-120 pmol/mg protein of cGMP and about 13 pmol/mg protein of cAMP. When the incubation in darkness was in calcium-deficient Earle's medium with 3 mM EGTA, a 10-20 fold increase occurred in the cGMP level, peaking at 2-3 min, but no change occurred in cAMP. This elevated level fell in 3 min to normal dark levels on return to normal Earle's medium, but was still about three times that of control levels after 15 min in EGTA-containing solution. Bright light after 2 min of dark incubation of dark-adapted retinas resulted in a 40-50% fall in cGMP, and bright light sharply reduced the elevated dark cGMP level of retinas in calcium-deficient media with 3 mM EDTA. However, no depression of normal dark levels of cGMP has thus far been obtained by increasing external calcium levels, even in the presence of the ionophore A23187. All the above phenomena involving dark cGMP levels and calcium are similar in Earle's medium with 100 mM of K+ substituted for Na+. Congenic rodless (rd/rd) mouse retinas have less than 5% of control cGMP and show only traces of calcium sensitivity. Thus, the above phenomena in controls are likely to be largely occurring in rods. The data suggest a dependency of the dark cGMP level on the calcium level, but that the light-induced fall in cGMP may largely be calcium insensitive.", "contents": "Calcium and cyclic nucleotide regulation in incubated mouse retinas. When retinas from dark-adapted C57BL/6 mice were incubated in the dark for 5 min at 37 degrees C in Earle's medium, they contained 80-120 pmol/mg protein of cGMP and about 13 pmol/mg protein of cAMP. When the incubation in darkness was in calcium-deficient Earle's medium with 3 mM EGTA, a 10-20 fold increase occurred in the cGMP level, peaking at 2-3 min, but no change occurred in cAMP. This elevated level fell in 3 min to normal dark levels on return to normal Earle's medium, but was still about three times that of control levels after 15 min in EGTA-containing solution. Bright light after 2 min of dark incubation of dark-adapted retinas resulted in a 40-50% fall in cGMP, and bright light sharply reduced the elevated dark cGMP level of retinas in calcium-deficient media with 3 mM EDTA. However, no depression of normal dark levels of cGMP has thus far been obtained by increasing external calcium levels, even in the presence of the ionophore A23187. All the above phenomena involving dark cGMP levels and calcium are similar in Earle's medium with 100 mM of K+ substituted for Na+. Congenic rodless (rd/rd) mouse retinas have less than 5% of control cGMP and show only traces of calcium sensitivity. Thus, the above phenomena in controls are likely to be largely occurring in rods. The data suggest a dependency of the dark cGMP level on the calcium level, but that the light-induced fall in cGMP may largely be calcium insensitive."}
{"id": "PMID:207817", "title": "The effect of heat-inactivated murine cytomegalovirus on host DNA synthesis of different cells.", "content": "Heat-inactivated murine cytomegalovirus (MCMV) stimulates cellular DNA synthesis in WME, NMG, 3T3, WgIA, chick and NIK-8 cells, but active or u.v.-irradiated MCMV does not. The stimulation of DNA synthesis in NIL-8 and chick cells was studied in detail. We found that both the nuclear and the mitochondrial DNA synthesis were stimulated in these cells. There was no virus DNA synthesis during the period we studied (48 h). The stimulation of nuclear DNA synthesis was about threefold in NIL-8 and 2.5-fold in chick cells as measured by the rate of incorporation of 3H-thymidine (3H-dThd) in the CsCl fractions which banded at the density of cell DNA. The stimulation was about 9.5-fold in NIL-8 and 1.7-fold in chick cells as detected by autoradiography. There was a 3-fold and a 2.2-fold increase in the degree of incorporation of 3H-dThd into mitochondrial DNA of NIL-8 and chick cells, respectively. The amount of mitochondrial DNA obtained in infected cells of both kinds was about twice that in control cells. The synthesis of mitochondrial DNA was also stimulated by a factor of 2 in the thymidine kinaseless 3T3 cells which incorporate exogenous thymidine exclusively into mitochondrial DNA. There were no MCMV specific antigens detectable by immunofluorescence 5 h after infection, but diffuse nuclear fluorescence could be demonstrated 24 h after infection. Our results indicate that the heat-inactivated virus penetrates the cells, stimulates host DNA synthesis and induces synthesis of early MCMV antigens.", "contents": "The effect of heat-inactivated murine cytomegalovirus on host DNA synthesis of different cells. Heat-inactivated murine cytomegalovirus (MCMV) stimulates cellular DNA synthesis in WME, NMG, 3T3, WgIA, chick and NIK-8 cells, but active or u.v.-irradiated MCMV does not. The stimulation of DNA synthesis in NIL-8 and chick cells was studied in detail. We found that both the nuclear and the mitochondrial DNA synthesis were stimulated in these cells. There was no virus DNA synthesis during the period we studied (48 h). The stimulation of nuclear DNA synthesis was about threefold in NIL-8 and 2.5-fold in chick cells as measured by the rate of incorporation of 3H-thymidine (3H-dThd) in the CsCl fractions which banded at the density of cell DNA. The stimulation was about 9.5-fold in NIL-8 and 1.7-fold in chick cells as detected by autoradiography. There was a 3-fold and a 2.2-fold increase in the degree of incorporation of 3H-dThd into mitochondrial DNA of NIL-8 and chick cells, respectively. The amount of mitochondrial DNA obtained in infected cells of both kinds was about twice that in control cells. The synthesis of mitochondrial DNA was also stimulated by a factor of 2 in the thymidine kinaseless 3T3 cells which incorporate exogenous thymidine exclusively into mitochondrial DNA. There were no MCMV specific antigens detectable by immunofluorescence 5 h after infection, but diffuse nuclear fluorescence could be demonstrated 24 h after infection. Our results indicate that the heat-inactivated virus penetrates the cells, stimulates host DNA synthesis and induces synthesis of early MCMV antigens."}
{"id": "PMID:207818", "title": "Relationship of endogenous murine xenotropic type C virus production to spontaneous transformation of cultured cells.", "content": "Spontaneous production of endogenous xenotropic viruses by clones of New Zealand Black (NZB) embryo cells occurs at a constant level even after several cell transfers. Foci of cell alteration occur spontaneously in some of the clonal lines after 6 to 10 passages. The amount of virus generated does not correlate with spontaneous transformation.. of these NZB cells nor of cells from NIH Swiss or BALB/c mice. The data demonstrate an intracellular regulation of xenotropic virus expression which remains stable over several cell generations and differs from that controlling cell transformation", "contents": "Relationship of endogenous murine xenotropic type C virus production to spontaneous transformation of cultured cells. Spontaneous production of endogenous xenotropic viruses by clones of New Zealand Black (NZB) embryo cells occurs at a constant level even after several cell transfers. Foci of cell alteration occur spontaneously in some of the clonal lines after 6 to 10 passages. The amount of virus generated does not correlate with spontaneous transformation.. of these NZB cells nor of cells from NIH Swiss or BALB/c mice. The data demonstrate an intracellular regulation of xenotropic virus expression which remains stable over several cell generations and differs from that controlling cell transformation"}
{"id": "PMID:207819", "title": "On the association of virus proteins with the nuclei of cells infected with herpes simplex virus.", "content": "In cells infected with herpes simplex virus, HSV-I, newly synthesized polypeptides accumulated in the nucleus at different rates, which did not change during the first 6 h after infection. Canavanine, an arginine analogue, prevented the nuclear accumulation of ICP (infected cell polypeptides) 5 and 8 and azetidine, a proline analogue, prevented that of ICP 5 and 7. The transfer of polypeptides to the nucleus was inhibited at 4 degrees C but not by dinitrophenol. Some of the nuclear polypeptides could be released by washing isolated nuclei with hypertonic salt solutions. ICP 17 was particularly sensitive to high salt treatment while ICP 5 and II were resistent. ICP 4b, a modified form of the alpha polypeptide ICP 4, was released by EDTA, and the detergent NP40 removed ICP II. Treatment of nuclei with DNase selectively reduced the amount of bound alpha polypeptides ICP 4c (the second modified form of ICP 4), 0 and 27 as well as ICP 8 and 25. Nuclei isolated from infected or uninfected cells and incubated in labelled cytoplasmic extracts took up primarily ICP 8 and 32. Alpha polypeptides were taken up to a lesser extent and ICP 6 and 10 were excluded. It is concluded that affinities for various constituents of host cell nuclei are likely to determine the nuclear accumulation of specific virus polypeptides.", "contents": "On the association of virus proteins with the nuclei of cells infected with herpes simplex virus. In cells infected with herpes simplex virus, HSV-I, newly synthesized polypeptides accumulated in the nucleus at different rates, which did not change during the first 6 h after infection. Canavanine, an arginine analogue, prevented the nuclear accumulation of ICP (infected cell polypeptides) 5 and 8 and azetidine, a proline analogue, prevented that of ICP 5 and 7. The transfer of polypeptides to the nucleus was inhibited at 4 degrees C but not by dinitrophenol. Some of the nuclear polypeptides could be released by washing isolated nuclei with hypertonic salt solutions. ICP 17 was particularly sensitive to high salt treatment while ICP 5 and II were resistent. ICP 4b, a modified form of the alpha polypeptide ICP 4, was released by EDTA, and the detergent NP40 removed ICP II. Treatment of nuclei with DNase selectively reduced the amount of bound alpha polypeptides ICP 4c (the second modified form of ICP 4), 0 and 27 as well as ICP 8 and 25. Nuclei isolated from infected or uninfected cells and incubated in labelled cytoplasmic extracts took up primarily ICP 8 and 32. Alpha polypeptides were taken up to a lesser extent and ICP 6 and 10 were excluded. It is concluded that affinities for various constituents of host cell nuclei are likely to determine the nuclear accumulation of specific virus polypeptides."}
{"id": "PMID:207820", "title": "Ribonucleoprotein-like structures from coronavirus particles.", "content": "The structure of the ribonucleoprotein (RNP) complex of three coronaviruses was investigated. A single-stranded helix of diam. 14 to 16 nm and up to 320 nm in length was released from disrupted particles of human coronavirus strain 229E and mouse hepatitis virus strain 3 after incubation in mild conditions. The helical complexes appeared to be composed of globular subunits with long axes of 5 to 7 nm surrounding a hollow core of diam. 3 to 4 nm. The complexes were shown to be sensitive to both pancreatic RNase and to pronase. No undegraded internal component was obtained from disrupted avian infectious bronchitis virus particles. We conclude that these structures are RNP complexes. The similarity between these RNPs and those of other large lipid containing RNA viruses is discussed.", "contents": "Ribonucleoprotein-like structures from coronavirus particles. The structure of the ribonucleoprotein (RNP) complex of three coronaviruses was investigated. A single-stranded helix of diam. 14 to 16 nm and up to 320 nm in length was released from disrupted particles of human coronavirus strain 229E and mouse hepatitis virus strain 3 after incubation in mild conditions. The helical complexes appeared to be composed of globular subunits with long axes of 5 to 7 nm surrounding a hollow core of diam. 3 to 4 nm. The complexes were shown to be sensitive to both pancreatic RNase and to pronase. No undegraded internal component was obtained from disrupted avian infectious bronchitis virus particles. We conclude that these structures are RNP complexes. The similarity between these RNPs and those of other large lipid containing RNA viruses is discussed."}
{"id": "PMID:207821", "title": "Evidence against the role of K+ in the shut-off of protein synthesis by vesicular stomatitis virus.", "content": "Intracellular K+ ion concentration and transport were measured in L cells infected with wild type VSV, which rapidly inhibits total protein synthesis in infected cells, and with a mutant, RI, defective in this function. No alterations in intracellular K+ ion concentration or transport were observed until late in infection and the late changes seen were similar for both viruses. Thus the inhibition of total protein synthesis by VSV cannot be ascribed to virus induced changes in host K+ ion concentration.", "contents": "Evidence against the role of K+ in the shut-off of protein synthesis by vesicular stomatitis virus. Intracellular K+ ion concentration and transport were measured in L cells infected with wild type VSV, which rapidly inhibits total protein synthesis in infected cells, and with a mutant, RI, defective in this function. No alterations in intracellular K+ ion concentration or transport were observed until late in infection and the late changes seen were similar for both viruses. Thus the inhibition of total protein synthesis by VSV cannot be ascribed to virus induced changes in host K+ ion concentration."}
{"id": "PMID:207822", "title": "Studies on the replication of KRV single-stranded linear DNA.", "content": "The autonomous parvovirus, Kilham rat virus (KRV), is composed of three structural proteins (Salzman & White, 1970) and a single molecule of DNA. The DNA molecule is linear and single-stranded (ss). It is believed to have both 3' and 5'-terminal palindromic sequences (Salzman, 1977). Replication of the ss DNA may involve double-stranded (ds) DNA intermediates of one unit length as found in the virion or multiple length concatamers (Salzman & White, 1973; Gunther & May, 1976; Lavelle & Li, 1977). We have attempted to determine when the synthesis of KRV ds DNA can be determined in synchronized infected cells and the structure of the ds DNA molecules.", "contents": "Studies on the replication of KRV single-stranded linear DNA. The autonomous parvovirus, Kilham rat virus (KRV), is composed of three structural proteins (Salzman & White, 1970) and a single molecule of DNA. The DNA molecule is linear and single-stranded (ss). It is believed to have both 3' and 5'-terminal palindromic sequences (Salzman, 1977). Replication of the ss DNA may involve double-stranded (ds) DNA intermediates of one unit length as found in the virion or multiple length concatamers (Salzman & White, 1973; Gunther & May, 1976; Lavelle & Li, 1977). We have attempted to determine when the synthesis of KRV ds DNA can be determined in synchronized infected cells and the structure of the ds DNA molecules."}
{"id": "PMID:207825", "title": "Determination of acetylcholine receptor antibody in myasthenia gravis: clinical usefulness and pathogenetic implications.", "content": "Antibodies to cholinergic receptor structures were found in 75% of 76 Finnish and 93% of 175 Swedish patients with myasthenia gravis. The amount of antibodies showed a positive correlation to the severity of the disease, and was reduced during immunosuppressive treatment, and by thymectomy. Thymoma patients had high values. The antibody was also found in the cerebrospinal fluid. Two healthy newborn babies of myasthenic mothers had antibodies during the first weeks of life, in spite of no clinical symptoms. The occurrence of IgM antibodies before IgM antibodies in two patients during the early stages of myasthenia gravis suggests that the antibody is not a primary cause of the disease.", "contents": "Determination of acetylcholine receptor antibody in myasthenia gravis: clinical usefulness and pathogenetic implications. Antibodies to cholinergic receptor structures were found in 75% of 76 Finnish and 93% of 175 Swedish patients with myasthenia gravis. The amount of antibodies showed a positive correlation to the severity of the disease, and was reduced during immunosuppressive treatment, and by thymectomy. Thymoma patients had high values. The antibody was also found in the cerebrospinal fluid. Two healthy newborn babies of myasthenic mothers had antibodies during the first weeks of life, in spite of no clinical symptoms. The occurrence of IgM antibodies before IgM antibodies in two patients during the early stages of myasthenia gravis suggests that the antibody is not a primary cause of the disease."}
{"id": "PMID:207826", "title": "Central nervous system susceptibility to herpes simplex infection.", "content": "Four days after inoculation of herpes simplex virus (HSV) on the rabbit cornea, distinctive and reproducible lesions appear in the trigeminal root entry zone. These viral lesions, situated in the central nervous system (CNS) portion of the root, consist of severe myelin destruction accompanied by mononuclear cell infiltration and partial sparing of axons. Immunofluorescent study demonstrated abundant viral antigen, and by electron microscopy viral nucleocapsids were found to be numerous within astrocytes and were rarely found in other cell types. In contrast, the adjacent peripheral nervous system (PNS) tissue appears unaffected by the presence of virus. The mechanism for this marked difference in response of the central nervous system and the peripheral nervous system may depend upon the susceptibility of astrocytes to viral infection and replication. The selective nature of the lesion provides an easily reproducible model for further investigation of the response of nervous system tissue to HSV.", "contents": "Central nervous system susceptibility to herpes simplex infection. Four days after inoculation of herpes simplex virus (HSV) on the rabbit cornea, distinctive and reproducible lesions appear in the trigeminal root entry zone. These viral lesions, situated in the central nervous system (CNS) portion of the root, consist of severe myelin destruction accompanied by mononuclear cell infiltration and partial sparing of axons. Immunofluorescent study demonstrated abundant viral antigen, and by electron microscopy viral nucleocapsids were found to be numerous within astrocytes and were rarely found in other cell types. In contrast, the adjacent peripheral nervous system (PNS) tissue appears unaffected by the presence of virus. The mechanism for this marked difference in response of the central nervous system and the peripheral nervous system may depend upon the susceptibility of astrocytes to viral infection and replication. The selective nature of the lesion provides an easily reproducible model for further investigation of the response of nervous system tissue to HSV."}
{"id": "PMID:207827", "title": "A second sensory--motor--interneuron with neurosecretory granules in Hydra.", "content": "Using serial-sectioning techniques for conventional transmission and high-voltage electron microscopy, we characterized the ultrastructural features and synaptic contacts of the sensory cell in tentacles of Hydra. The sensory cell has an apical specialization characterized by a recessed cilium surrounded by three rodlike stereocilia. This ciliary--stereociliary complex constitutes the receptive or dendritic pole of the sensory cell. The dense filamentous cores of the stereocilia project proximally into a narrow circumciliary cytoplasmic region connected by septate junctions to marginal processes of an enveloping epitheliomuscular cell. The central cilium has a characteristic marginal flare midway along its length and a dense filamentous substructure at its base. Pairs of branched, striated rootlets extend from the axial centriole into a mitochondria-rich region of the cell. Pigment-like granules are present in the cytoplasm around the circumciliary space. The perikaryon is characterized by an elongate nucleus surrounded by a narrow rim of cytoplasm containing prominent Golgi complexes, assorted vacuoles and dense-cored vesicles, free ribosomes, short segments of rough endoplasmic reticulum, microtubules, glycogen particles, and lipid droplets. Generally, one or two thin, naked axons extend laterally from the perikaryon into the nerve net region above the myonemes of the large epitheliomuscular cells. Within the axons are found occasional aggregates of dense-cored vesicles and en passant synapses characterized by the presence of clear or dense-cored vesicles in contact with paramembranous densities and associated intracleft cross filaments. Using these ultrastructural criteria, we demonstrated for the first time that the granule-containing sensory cells have synaptic contacts with other neurons, nematocytes, and epitheliomuscular cells hence, we considered these cells to be sensory--motor--interneurons with neurosecretory granules. We hypothesize that this unique, apparently multifunctional neuron may be a modern representative of a primitive stem cell that give rise evolutionarily to the sensory cells, motor neurons, interneurons, and neurosecretory cells of higher animals.", "contents": "A second sensory--motor--interneuron with neurosecretory granules in Hydra. Using serial-sectioning techniques for conventional transmission and high-voltage electron microscopy, we characterized the ultrastructural features and synaptic contacts of the sensory cell in tentacles of Hydra. The sensory cell has an apical specialization characterized by a recessed cilium surrounded by three rodlike stereocilia. This ciliary--stereociliary complex constitutes the receptive or dendritic pole of the sensory cell. The dense filamentous cores of the stereocilia project proximally into a narrow circumciliary cytoplasmic region connected by septate junctions to marginal processes of an enveloping epitheliomuscular cell. The central cilium has a characteristic marginal flare midway along its length and a dense filamentous substructure at its base. Pairs of branched, striated rootlets extend from the axial centriole into a mitochondria-rich region of the cell. Pigment-like granules are present in the cytoplasm around the circumciliary space. The perikaryon is characterized by an elongate nucleus surrounded by a narrow rim of cytoplasm containing prominent Golgi complexes, assorted vacuoles and dense-cored vesicles, free ribosomes, short segments of rough endoplasmic reticulum, microtubules, glycogen particles, and lipid droplets. Generally, one or two thin, naked axons extend laterally from the perikaryon into the nerve net region above the myonemes of the large epitheliomuscular cells. Within the axons are found occasional aggregates of dense-cored vesicles and en passant synapses characterized by the presence of clear or dense-cored vesicles in contact with paramembranous densities and associated intracleft cross filaments. Using these ultrastructural criteria, we demonstrated for the first time that the granule-containing sensory cells have synaptic contacts with other neurons, nematocytes, and epitheliomuscular cells hence, we considered these cells to be sensory--motor--interneurons with neurosecretory granules. We hypothesize that this unique, apparently multifunctional neuron may be a modern representative of a primitive stem cell that give rise evolutionarily to the sensory cells, motor neurons, interneurons, and neurosecretory cells of higher animals."}
{"id": "PMID:207828", "title": "Control of pedal and parapodial movements in Aplysia. II. Cerebral ganglion neurons.", "content": "1. Intracellular stimulation of individual neurons in the two symmetrical A neuron clusters of the cerebral ganglion evoked contractions of both the foot and parapodia. Electrical stimulation of pedal and parapodial nerves caused antidromic action potentials in A neurons. Units recorded in the nerves followed the driven somatic spike 1:1. This suggests that the A neurons are presumptive pedal and parapodial motor neurons.2. Individual A neurons evoked both bilteral and unilateral contractions of the parapodia or split foot. Contractions in the parapodia were independent of those in the foot. An individual A neuron caused contractions in either the foot or the parapodia, but not both. Sequential transection of parapodial nerves had only a slight effect until a key nerve was cut. The contractions produced by a single A neuron on one side were then abolished. These data suggest that the motor fields of the A neurons are well defined within the foot or the parapodia. 3. Parapodial contractions produced by individual A neurons are not dependent on the excitation of follower motor neurons. Blocking synaptic transmission by the addition of CoCl2 did not eliminate the contractions produced by driving individual A neurons. This is consistent with the A neurons being motor neurons. 4. Intracellular stimulation of individual neurons in the symmetrical B neuron clusters of the cerebral ganglion also evoked pedal and parapodial contractions. Electrical stimulation of the pedal and parapodial nerves elicited antidromic spikes in these neurons. Individual B neurons caused contractions in both the foot and parapodia. This suggests that the B neurons are motor neurons with very large motor fields. 5. Filling the pedal and parapodial nerves with cobalt primarily filled the cell bodies of neurons located in the pedal and pleural ganglia. The somata of A and B neurons were also occasionally filled. This is consistent with the electrophisiological results. 6. Other neurons also evoked parapodial contractions. Intracellular stimulation of neurons in the pedal and pleural ganglia caused parapodial contractions in intact animals. Some of these neurons were excited by stretching the parapodia or touching the tentacles. 7. The B neurons are strongly excited by tactile stimulation of the tentacles. Since they can cause pedal and parapodial contractions they may mediate reflex contractions elicited by tentacular stimulation. Stretching the parapodia only occasionally caused the A neurons to fire. This makes it unlikely that they make a major contribution to pedal and parapodial proprioceptive reflexes. These reflexes are probably controlled by neurons in the pedal and pleural ganglia.", "contents": "Control of pedal and parapodial movements in Aplysia. II. Cerebral ganglion neurons. 1. Intracellular stimulation of individual neurons in the two symmetrical A neuron clusters of the cerebral ganglion evoked contractions of both the foot and parapodia. Electrical stimulation of pedal and parapodial nerves caused antidromic action potentials in A neurons. Units recorded in the nerves followed the driven somatic spike 1:1. This suggests that the A neurons are presumptive pedal and parapodial motor neurons.2. Individual A neurons evoked both bilteral and unilateral contractions of the parapodia or split foot. Contractions in the parapodia were independent of those in the foot. An individual A neuron caused contractions in either the foot or the parapodia, but not both. Sequential transection of parapodial nerves had only a slight effect until a key nerve was cut. The contractions produced by a single A neuron on one side were then abolished. These data suggest that the motor fields of the A neurons are well defined within the foot or the parapodia. 3. Parapodial contractions produced by individual A neurons are not dependent on the excitation of follower motor neurons. Blocking synaptic transmission by the addition of CoCl2 did not eliminate the contractions produced by driving individual A neurons. This is consistent with the A neurons being motor neurons. 4. Intracellular stimulation of individual neurons in the symmetrical B neuron clusters of the cerebral ganglion also evoked pedal and parapodial contractions. Electrical stimulation of the pedal and parapodial nerves elicited antidromic spikes in these neurons. Individual B neurons caused contractions in both the foot and parapodia. This suggests that the B neurons are motor neurons with very large motor fields. 5. Filling the pedal and parapodial nerves with cobalt primarily filled the cell bodies of neurons located in the pedal and pleural ganglia. The somata of A and B neurons were also occasionally filled. This is consistent with the electrophisiological results. 6. Other neurons also evoked parapodial contractions. Intracellular stimulation of neurons in the pedal and pleural ganglia caused parapodial contractions in intact animals. Some of these neurons were excited by stretching the parapodia or touching the tentacles. 7. The B neurons are strongly excited by tactile stimulation of the tentacles. Since they can cause pedal and parapodial contractions they may mediate reflex contractions elicited by tentacular stimulation. Stretching the parapodia only occasionally caused the A neurons to fire. This makes it unlikely that they make a major contribution to pedal and parapodial proprioceptive reflexes. These reflexes are probably controlled by neurons in the pedal and pleural ganglia."}
{"id": "PMID:207829", "title": "Evidence for nonsynaptic neuronal interaction.", "content": "1. Evidence is presented that synaptic interactions within and between the statocyst and visual pathways of Hermissenda are eliminated after 0.5-4 min exposure to 20-40 mM Co2+. 2. Synaptic blockade was also produced by perfusion with low Ca2+ (5mM) plus 10-20 mM Co2+. 3. Depolarization of hair cells by impulses of type A photoreceptors remains after the same exposure to Co2+, or low Ca2+ plus Co2+. 4. The increased resistance previously observed during this depolarization of hair cells cannot be observed after exposure to Co2+. 5. The depolarization which remains after exposure to Co2+ did not change with different levels of membrane potential from -20 mV below to +10 mV above the resting level. 6. The time course of potassium accumulation, monitored by the amplitude of the type A impulse afterpotential, closely followed the time course of hair cell depolarization and also of changes in the amplitude of the hair cell afterpotential. 7. The depolarization of hair cells by type A impulses decreased with increased extracellular potassium, but was only slightly reduced by lowered extracellular potassium. 8. The amount of potassium accumulation following a type A impulse train could be estimated from the effects of changes in extracellular potassium in the perfusate on the type A impulse afterpotential. From this extimated increase of extracellular potassium it was possible to predict with some accuracy, the observed hair cell depolarization. 9. Although type A cells are not electrically coupled to ipsilateral hair cells, firing of these hair cells slightly depolarized the type A photoreceptor which excites them. 10. Strophanthidin (10-4 M) did not block the depolarization of hair cells by type A impulses. 11. The data are evidence for nonsynaptic excitation of hair cells by type A photoreceptor impulses. The data are also consistent with the interpretation that the excitation arises from potassium accumulation around the type A and hair cell axonal membranes.", "contents": "Evidence for nonsynaptic neuronal interaction. 1. Evidence is presented that synaptic interactions within and between the statocyst and visual pathways of Hermissenda are eliminated after 0.5-4 min exposure to 20-40 mM Co2+. 2. Synaptic blockade was also produced by perfusion with low Ca2+ (5mM) plus 10-20 mM Co2+. 3. Depolarization of hair cells by impulses of type A photoreceptors remains after the same exposure to Co2+, or low Ca2+ plus Co2+. 4. The increased resistance previously observed during this depolarization of hair cells cannot be observed after exposure to Co2+. 5. The depolarization which remains after exposure to Co2+ did not change with different levels of membrane potential from -20 mV below to +10 mV above the resting level. 6. The time course of potassium accumulation, monitored by the amplitude of the type A impulse afterpotential, closely followed the time course of hair cell depolarization and also of changes in the amplitude of the hair cell afterpotential. 7. The depolarization of hair cells by type A impulses decreased with increased extracellular potassium, but was only slightly reduced by lowered extracellular potassium. 8. The amount of potassium accumulation following a type A impulse train could be estimated from the effects of changes in extracellular potassium in the perfusate on the type A impulse afterpotential. From this extimated increase of extracellular potassium it was possible to predict with some accuracy, the observed hair cell depolarization. 9. Although type A cells are not electrically coupled to ipsilateral hair cells, firing of these hair cells slightly depolarized the type A photoreceptor which excites them. 10. Strophanthidin (10-4 M) did not block the depolarization of hair cells by type A impulses. 11. The data are evidence for nonsynaptic excitation of hair cells by type A photoreceptor impulses. The data are also consistent with the interpretation that the excitation arises from potassium accumulation around the type A and hair cell axonal membranes."}
{"id": "PMID:207830", "title": "Neuronal transmission through hippocampal pathways dependent on behavior.", "content": "1. In chronically prepared, freely moving rats, electrical stimulation was applied to the angular bundle, and responses were recorded extracellularly at a variety of sites in the ipsilateral hippocampal formation. At each recording site the stimulus-response relationship was tested during four different behavioral states. These were slow-wave sleep (SWS), REM sleep ( REM), and also two waking behaviors consisting of the still, alert condition (labeled SAL), and voluntary movement (AW theta). 2. Two varieties of evoked responses were recorded: those due to the synchronous firing of neuronal action potentials (EAPs) and those produced by excitatory synaptic activity (ESPs). The overall pattern of monosynaptic, di-, and trisynaptic responses found was similar in the rat to that found by Andersen et al. (3-5) in cat and rabbit. 3. When the trisynaptic EAP was recorded in CA1, the threshold was similar during all four behavioral states. However, suprathreshold stimuli evoked a greater response during SWS than during the other three states. The trisynaptic ESP was also greater during SWS. 4. Disynaptically, EAPs were recorded in CA3. These were greater in magnitude during SWS than during SAL, but were intermediate in mean amplitude during AWtheta and REM. Response variability was much greater during AWtheta and REM. 5. The monosynaptic EAP recorded in the upper blade of the dentate gyrus (DG) exhibited the same behaviorally correlated properties found disynaptically in CA3. 6. The monosynaptic ESP recorded in the DG, in contrast to the EAP, was greater in magnitude during SAL than during SWS. 7. The primary afferent volley was also recorded at high gain in the DG. The amplitude of this was found to be dependent solely on stimulus intensity and not on behavioral state. 8. The results are interpreted as suggesting that the granule cell membranes in the DG are relatively hyperpolarized during SAL compared with SWS as the result of either tonic excitatory bombardment occurring during SWS or tonic inhibitory bombardment during SAL.", "contents": "Neuronal transmission through hippocampal pathways dependent on behavior. 1. In chronically prepared, freely moving rats, electrical stimulation was applied to the angular bundle, and responses were recorded extracellularly at a variety of sites in the ipsilateral hippocampal formation. At each recording site the stimulus-response relationship was tested during four different behavioral states. These were slow-wave sleep (SWS), REM sleep ( REM), and also two waking behaviors consisting of the still, alert condition (labeled SAL), and voluntary movement (AW theta). 2. Two varieties of evoked responses were recorded: those due to the synchronous firing of neuronal action potentials (EAPs) and those produced by excitatory synaptic activity (ESPs). The overall pattern of monosynaptic, di-, and trisynaptic responses found was similar in the rat to that found by Andersen et al. (3-5) in cat and rabbit. 3. When the trisynaptic EAP was recorded in CA1, the threshold was similar during all four behavioral states. However, suprathreshold stimuli evoked a greater response during SWS than during the other three states. The trisynaptic ESP was also greater during SWS. 4. Disynaptically, EAPs were recorded in CA3. These were greater in magnitude during SWS than during SAL, but were intermediate in mean amplitude during AWtheta and REM. Response variability was much greater during AWtheta and REM. 5. The monosynaptic EAP recorded in the upper blade of the dentate gyrus (DG) exhibited the same behaviorally correlated properties found disynaptically in CA3. 6. The monosynaptic ESP recorded in the DG, in contrast to the EAP, was greater in magnitude during SAL than during SWS. 7. The primary afferent volley was also recorded at high gain in the DG. The amplitude of this was found to be dependent solely on stimulus intensity and not on behavioral state. 8. The results are interpreted as suggesting that the granule cell membranes in the DG are relatively hyperpolarized during SAL compared with SWS as the result of either tonic excitatory bombardment occurring during SWS or tonic inhibitory bombardment during SAL."}
{"id": "PMID:207831", "title": "Death following external carotid artery embolization for a functioning glomus jugulare chemodectoma. Case report.", "content": "A 24-year-old man with left sixth through twelfth cranial nerve palsies and severe, fluctuating, systemic arterial hypertension was found to have a large, vascular, catecholamine-forming glomus jugulare chemodectoma. After his electrolyte imbalance was corrected, left external carotid embolization (using Gelfoam) was carried out. The systemic blood pressure stabilized at around 160/100 mm Hg over the next 12 hours. Ten hours later the hitherto conscious patient developed acute arterial hypotension, lapsed into coma, and died. Autopsy showed tumor infarction, swelling, cerebellar tonsillar herniation, and medullary compression. An unusual complication of glomus tumor embolization is highlighted. The roles of preliminary decompressive surgery and urgent resuscitation by vasopressors are discussed.", "contents": "Death following external carotid artery embolization for a functioning glomus jugulare chemodectoma. Case report. A 24-year-old man with left sixth through twelfth cranial nerve palsies and severe, fluctuating, systemic arterial hypertension was found to have a large, vascular, catecholamine-forming glomus jugulare chemodectoma. After his electrolyte imbalance was corrected, left external carotid embolization (using Gelfoam) was carried out. The systemic blood pressure stabilized at around 160/100 mm Hg over the next 12 hours. Ten hours later the hitherto conscious patient developed acute arterial hypotension, lapsed into coma, and died. Autopsy showed tumor infarction, swelling, cerebellar tonsillar herniation, and medullary compression. An unusual complication of glomus tumor embolization is highlighted. The roles of preliminary decompressive surgery and urgent resuscitation by vasopressors are discussed."}
{"id": "PMID:207832", "title": "Transsphenoidal microsurgery for pituitary tumors associated with hyperprolactinemia.", "content": "The results of transsphenoidal microsurgery in treating 37 patients (30 women and seven men) with pituitary tumors associated with hyperprolactinemia are presented. Immediate (10-day) postoperative fasting prolactin levels were normal (less than 25 ng/ml) in 19 of 26 patients whose preoperative prolactin level was less than 200 ng/ml, and in only three of 11 patients in whom preoperative prolactin was greater than 200 ng/ml. Twelve of 13 patients with normal preoperative pituitary-target organ function maintained normal axes postoperatively. Thirteen other patients had preoperative deficiencies in one or more pituitary-target organ axes. Postoperatively, in these latter 13 patients, a pituitary-target organ axis that was deficient preoperatively returned to normal in six cases; there was no change in five, and there was impairment in another axis in four instances. Although gross total tumor removal was believed to be complete in 35 of 37 patients, serial postoperative prolactin determinations in four of these 35 patients indicate tumor regrowth. The authors conclude that transsphenoidal microsurgery is currently the operative procedure of choice for the majority of pituitary tumors associated with hyperprolactinemia.", "contents": "Transsphenoidal microsurgery for pituitary tumors associated with hyperprolactinemia. The results of transsphenoidal microsurgery in treating 37 patients (30 women and seven men) with pituitary tumors associated with hyperprolactinemia are presented. Immediate (10-day) postoperative fasting prolactin levels were normal (less than 25 ng/ml) in 19 of 26 patients whose preoperative prolactin level was less than 200 ng/ml, and in only three of 11 patients in whom preoperative prolactin was greater than 200 ng/ml. Twelve of 13 patients with normal preoperative pituitary-target organ function maintained normal axes postoperatively. Thirteen other patients had preoperative deficiencies in one or more pituitary-target organ axes. Postoperatively, in these latter 13 patients, a pituitary-target organ axis that was deficient preoperatively returned to normal in six cases; there was no change in five, and there was impairment in another axis in four instances. Although gross total tumor removal was believed to be complete in 35 of 37 patients, serial postoperative prolactin determinations in four of these 35 patients indicate tumor regrowth. The authors conclude that transsphenoidal microsurgery is currently the operative procedure of choice for the majority of pituitary tumors associated with hyperprolactinemia."}
{"id": "PMID:207833", "title": "Fast-neutron irradiation of glioblastoma multiforme. Neuropathological analysis.", "content": "Various modes of therapy, alone or in combination, have had little effect in improving the survival of patients with glioblastoma multiforme. Recently, in a pilot study, 34 patients with glioblastoma were treated by fast-neutron-beam irradiation of the whole brain. Following treatment, the patients became steroid-dependent and pursued a gradual downhill course with increasing obtundation. Although there was no improvement in the length or quality of survival of these patients, neuropathological studies in the 13 patients who came to autopsy showed the following: 1) extensive coagulative necrosis of much of the tumor mass; 2) dense infiltration by collagenous connective tissue; 3) minimal phagocytic reaction; 4) marked reduction in the amount of viable tumor; 5) abnormal astrocytic proliferation, which may represent either astrocytoma or a radiation-induced bizarre gliosis, and 6) areas of gliosis and white matter degeneration in the brain stem, remote form the tumor site. These observations suggest that continued efforts to further refine this mode of therapy for glioblastoma are warranted.", "contents": "Fast-neutron irradiation of glioblastoma multiforme. Neuropathological analysis. Various modes of therapy, alone or in combination, have had little effect in improving the survival of patients with glioblastoma multiforme. Recently, in a pilot study, 34 patients with glioblastoma were treated by fast-neutron-beam irradiation of the whole brain. Following treatment, the patients became steroid-dependent and pursued a gradual downhill course with increasing obtundation. Although there was no improvement in the length or quality of survival of these patients, neuropathological studies in the 13 patients who came to autopsy showed the following: 1) extensive coagulative necrosis of much of the tumor mass; 2) dense infiltration by collagenous connective tissue; 3) minimal phagocytic reaction; 4) marked reduction in the amount of viable tumor; 5) abnormal astrocytic proliferation, which may represent either astrocytoma or a radiation-induced bizarre gliosis, and 6) areas of gliosis and white matter degeneration in the brain stem, remote form the tumor site. These observations suggest that continued efforts to further refine this mode of therapy for glioblastoma are warranted."}
{"id": "PMID:207834", "title": "The distribution of nuclear DNA from human brain-tumor cells.", "content": "Flow cytometry (FCM) is a technique that measures the quantity of DNA contained in individual nuclei and records a frequency distribution of the DNA content per nucleus in the sampled cell population. Nuclei from a variety of human brain-tumor types were isolated by means of tissue grinding, purified by centrifugation through 40% sucrose (15 minutes at 4000 rpm), fixed with 10% formalin, stained with acriflavin-Feulgen, and analyzed by FCM. Profiles of DNA distribution in histologically benign tumors, such as meningiomas, pituitary adenomas, neuroblastomas, and low-grade astrocytomas, revealed a large diploid population (2C) with a few nuclei in DNA synthesis, as well as a small premitotic population (G2 cells) that contains a 4C DNA complement. In contrast, malignant gliomas, including glioblastomas, consist of more cells in DNA synthesis; these tumor cells show a highly variable distribution of ploidy consisting not only of diploid, and/or aneuploid, but also of triploid, tetraploid, and possibly octaploid populations. Also, a large variability between different regions of each tumor was always observed. In contrast, metastatic brain tumors, despite the fact that they contain a considerable number of cells undergoing DNA synthesis, demonstrate little variability within each individual tumor. The ability to rapidly characterize the cell populations of human brain tumors with FCM may enhance the effectiveness of their clinical management.", "contents": "The distribution of nuclear DNA from human brain-tumor cells. Flow cytometry (FCM) is a technique that measures the quantity of DNA contained in individual nuclei and records a frequency distribution of the DNA content per nucleus in the sampled cell population. Nuclei from a variety of human brain-tumor types were isolated by means of tissue grinding, purified by centrifugation through 40% sucrose (15 minutes at 4000 rpm), fixed with 10% formalin, stained with acriflavin-Feulgen, and analyzed by FCM. Profiles of DNA distribution in histologically benign tumors, such as meningiomas, pituitary adenomas, neuroblastomas, and low-grade astrocytomas, revealed a large diploid population (2C) with a few nuclei in DNA synthesis, as well as a small premitotic population (G2 cells) that contains a 4C DNA complement. In contrast, malignant gliomas, including glioblastomas, consist of more cells in DNA synthesis; these tumor cells show a highly variable distribution of ploidy consisting not only of diploid, and/or aneuploid, but also of triploid, tetraploid, and possibly octaploid populations. Also, a large variability between different regions of each tumor was always observed. In contrast, metastatic brain tumors, despite the fact that they contain a considerable number of cells undergoing DNA synthesis, demonstrate little variability within each individual tumor. The ability to rapidly characterize the cell populations of human brain tumors with FCM may enhance the effectiveness of their clinical management."}
{"id": "PMID:207836", "title": "Metabolism of fatty acids and the levels of ketone bodies in the livers of pyridoxine-deficient rats.", "content": "Lipid metabolism was examined in rats fed a high-protein pyridoxine-deficient diet, and their livers were found to contain large amounts of lipids, mainly in the forms of triglycerides and cholesteryl ester. The contents of ketone bodies in the livers of pyridoxine-deficient and the control rats were similar. Their NAD+/NADH ratios, calculated from the amounts of ketone bodies, were also similar in pyridoxine-deficient and control groups when the animals were fed, but the ratio in pyridoxine-deficient rats was lower than that of control rats when the animals were starved. After injection of 14C-linoleic acid, the amounts of expired 14CO2 in pyridoxine-deficient and control rats were similar. The pattern of incorporations of 14C-linoleic acid into various lipid components of the livers were examined; incorporation into the phospho-lipid fraction was similar in control and deficient rats, but the incorporation into the triglyceride fraction was slower, and the incorporation into cholesterol was faster in deficient animals than in controls.", "contents": "Metabolism of fatty acids and the levels of ketone bodies in the livers of pyridoxine-deficient rats. Lipid metabolism was examined in rats fed a high-protein pyridoxine-deficient diet, and their livers were found to contain large amounts of lipids, mainly in the forms of triglycerides and cholesteryl ester. The contents of ketone bodies in the livers of pyridoxine-deficient and the control rats were similar. Their NAD+/NADH ratios, calculated from the amounts of ketone bodies, were also similar in pyridoxine-deficient and control groups when the animals were fed, but the ratio in pyridoxine-deficient rats was lower than that of control rats when the animals were starved. After injection of 14C-linoleic acid, the amounts of expired 14CO2 in pyridoxine-deficient and control rats were similar. The pattern of incorporations of 14C-linoleic acid into various lipid components of the livers were examined; incorporation into the phospho-lipid fraction was similar in control and deficient rats, but the incorporation into the triglyceride fraction was slower, and the incorporation into cholesterol was faster in deficient animals than in controls."}
{"id": "PMID:207837", "title": "In vivo and in vitro conversion of 7-dehydrocholesterol into vitamin D3 in rat skin by ultraviolet ray's irradiation.", "content": "In order to confirm the photochemical conversion of 7-dehydrocholesterol (7-DHC) into vitamin D3 in rat skin, the following in vitro and in vivo experiments were carried out. In the first (in vitro) experiment, the skin stripped off from a sacrificed normal rat was irradiated with an ultraviolet (UV) lamp for a constant period. In the second (in vivo) experiment, the normal rat, irradiated under the same condition mentioned above, was sacrificed and then the skin was stripped off. Lipids were individually extracted with chloroform-methanol (1:1) from the skin obtained in the two experiments and the solvent was evaporated. The resulting residue was saponified and the unsaponifiable matter extracted with benzene was purified by application to hydroxyalkoxy-propyl (HAP) Sephadex column chromatography. The resulting purified vitamin D3 fraction was applied to high-performance liquid chromatography (HPLC) in order to estimate vitamin D3. No peak, aside from that of alpha-naphthol as an internal standard, was observed in the HPLC chromatogram on the skin obtained from the non-irradiated rat, whereas the peak corresponding to vitamin D3 was observed in each HPLC chromatogram on both the irradiated skin (in vitro experiment) and the skin obtained from the irradiated rat (in vivo experiment). The peaks, confirmed to be due to vitamin D3 by the results of co-chromatography, were increased according to the increase of irradiation energy and there were little differences between the corresponding estimated values of vitamin D3 in the two experiments. These results prompted the conclusion that 7-DHC in rat skin was photochemically converted into vitamin D3 by UV irradiation and that the in vivo conversion mechanism might be the same as the in vitro one.", "contents": "In vivo and in vitro conversion of 7-dehydrocholesterol into vitamin D3 in rat skin by ultraviolet ray's irradiation. In order to confirm the photochemical conversion of 7-dehydrocholesterol (7-DHC) into vitamin D3 in rat skin, the following in vitro and in vivo experiments were carried out. In the first (in vitro) experiment, the skin stripped off from a sacrificed normal rat was irradiated with an ultraviolet (UV) lamp for a constant period. In the second (in vivo) experiment, the normal rat, irradiated under the same condition mentioned above, was sacrificed and then the skin was stripped off. Lipids were individually extracted with chloroform-methanol (1:1) from the skin obtained in the two experiments and the solvent was evaporated. The resulting residue was saponified and the unsaponifiable matter extracted with benzene was purified by application to hydroxyalkoxy-propyl (HAP) Sephadex column chromatography. The resulting purified vitamin D3 fraction was applied to high-performance liquid chromatography (HPLC) in order to estimate vitamin D3. No peak, aside from that of alpha-naphthol as an internal standard, was observed in the HPLC chromatogram on the skin obtained from the non-irradiated rat, whereas the peak corresponding to vitamin D3 was observed in each HPLC chromatogram on both the irradiated skin (in vitro experiment) and the skin obtained from the irradiated rat (in vivo experiment). The peaks, confirmed to be due to vitamin D3 by the results of co-chromatography, were increased according to the increase of irradiation energy and there were little differences between the corresponding estimated values of vitamin D3 in the two experiments. These results prompted the conclusion that 7-DHC in rat skin was photochemically converted into vitamin D3 by UV irradiation and that the in vivo conversion mechanism might be the same as the in vitro one."}
{"id": "PMID:207838", "title": "Mixed tumor of skin.", "content": "A 40-year-old white male consulted his dentist because of a mass in the upper lip to the right of the midline. The patient stated that the lesion had been present and slowly enlarging for at least the pat 10 years. A mass that appeared to be about the size of a hazel nut was apparent to direct visualization and it produced an elevation of the lip surface. On palpation, the mass was found to have a firm rubbery texture and to be freely movable. The history of slow growth of an apparently well delineated mass over a lengthy period of time, together with a lack of fixation to the surrounding tissues of the lip was considered indicative of a benign lesion. The mass was extirpated using an intraoral approach under local anesthesia.", "contents": "Mixed tumor of skin. A 40-year-old white male consulted his dentist because of a mass in the upper lip to the right of the midline. The patient stated that the lesion had been present and slowly enlarging for at least the pat 10 years. A mass that appeared to be about the size of a hazel nut was apparent to direct visualization and it produced an elevation of the lip surface. On palpation, the mass was found to have a firm rubbery texture and to be freely movable. The history of slow growth of an apparently well delineated mass over a lengthy period of time, together with a lack of fixation to the surrounding tissues of the lip was considered indicative of a benign lesion. The mass was extirpated using an intraoral approach under local anesthesia."}
{"id": "PMID:207843", "title": "Polydipsia, polyuria, and hypertension associated with renin-secreting Wilms tumor.", "content": "A 16-month-old black male infant had unusual thirst, polyuria, hyponatremia, and hypertension. His polyuria was unresponsive to vasopressin therapy, and his high blood pressure was not effectively controlled by antihypertensive drugs. Radiographic examinations revealed an occult Wilms tumor in the right kidney. After removal of the tumor, the signs and symptoms were relieved. The tumor had a renin activity about 280 times that of the adjacent renal cortex, and many intracytoplasmic secretory granules were found on electron microscopy. The pathogenesis of these clinical manifestations appears to be mediated through the physiologic pathways of renin-angiotensin II and renin-aldosterone.", "contents": "Polydipsia, polyuria, and hypertension associated with renin-secreting Wilms tumor. A 16-month-old black male infant had unusual thirst, polyuria, hyponatremia, and hypertension. His polyuria was unresponsive to vasopressin therapy, and his high blood pressure was not effectively controlled by antihypertensive drugs. Radiographic examinations revealed an occult Wilms tumor in the right kidney. After removal of the tumor, the signs and symptoms were relieved. The tumor had a renin activity about 280 times that of the adjacent renal cortex, and many intracytoplasmic secretory granules were found on electron microscopy. The pathogenesis of these clinical manifestations appears to be mediated through the physiologic pathways of renin-angiotensin II and renin-aldosterone."}
{"id": "PMID:207846", "title": "The biochemical basis for resistance to adenine arabinoside in a mutant of Toxoplasma gondii.", "content": "We have previously reported the isolation and preliminary characterization of a mutant of Toxoplasma gondii that was resistant to adenine arabinoside. Fiftyfold higher concentrations of adenine arabinoside were required to inhibit the growth of the resistant parasite in human fibroblast cultures. To determine the enzymic basis for resistance, we measured the kinases and deaminases that act on adenosine or deoxyadenosine. All of these enzymic activities were found in uninfected human fibroblast cells. The mutant and wild type parasite proved to have similar activities of adenosine deaminase, deoxyadenosine deaminase, and deoxyadenosine kinase. However, the adenine arabinoside resistant mutant had less than 0.1% of the adenosine kinase activity observed in the wild type T. gondii. The mutant parasite is presumably resistant because without adenosine kinase to phosphorylate adenine arabinoside it cannot carry out the first step in the conversion of the analogue to adenine arabinoside triphosphate, the active form. A mutant of 3T6 (mouse) cells previously selected for a loss of adenosine kinase also proved to be resistant to adenine arabinoside.", "contents": "The biochemical basis for resistance to adenine arabinoside in a mutant of Toxoplasma gondii. We have previously reported the isolation and preliminary characterization of a mutant of Toxoplasma gondii that was resistant to adenine arabinoside. Fiftyfold higher concentrations of adenine arabinoside were required to inhibit the growth of the resistant parasite in human fibroblast cultures. To determine the enzymic basis for resistance, we measured the kinases and deaminases that act on adenosine or deoxyadenosine. All of these enzymic activities were found in uninfected human fibroblast cells. The mutant and wild type parasite proved to have similar activities of adenosine deaminase, deoxyadenosine deaminase, and deoxyadenosine kinase. However, the adenine arabinoside resistant mutant had less than 0.1% of the adenosine kinase activity observed in the wild type T. gondii. The mutant parasite is presumably resistant because without adenosine kinase to phosphorylate adenine arabinoside it cannot carry out the first step in the conversion of the analogue to adenine arabinoside triphosphate, the active form. A mutant of 3T6 (mouse) cells previously selected for a loss of adenosine kinase also proved to be resistant to adenine arabinoside."}
{"id": "PMID:207847", "title": "Ultrastructure of erythrocytes parasitized by Haemobartonella felis.", "content": "Experimental Haemobartonella felis infections were studied in 3 mature, intact cats by examining peripheral blood, lung, and spleen by electron microscopy. Coccoid, rod, or ring forms of the organism were found on or close to the erythrocytic membrane, and adjacent parasitized erythrocytes often were attached. Intracytoplasmic crystalloid inclusions occupying most of erythrocytic cytoplasm were seen in the 3 infected cats. The cat with the highest parasitemia had inclusions in about 10% of the erythrocytes. Less than 0.01% of the erythrocytes of a control cat contained inclusions. Parasitized erythrocytes, with and without inclusions, were seen in capillaries of the lung and spleen of infected cats. Macrophages in the lung and spleen of infected cats contained parasitized erythrocytes, either with or without inclusions. Some macrophages contained erythrocyte-free organisms in phagocytic vacuoles.", "contents": "Ultrastructure of erythrocytes parasitized by Haemobartonella felis. Experimental Haemobartonella felis infections were studied in 3 mature, intact cats by examining peripheral blood, lung, and spleen by electron microscopy. Coccoid, rod, or ring forms of the organism were found on or close to the erythrocytic membrane, and adjacent parasitized erythrocytes often were attached. Intracytoplasmic crystalloid inclusions occupying most of erythrocytic cytoplasm were seen in the 3 infected cats. The cat with the highest parasitemia had inclusions in about 10% of the erythrocytes. Less than 0.01% of the erythrocytes of a control cat contained inclusions. Parasitized erythrocytes, with and without inclusions, were seen in capillaries of the lung and spleen of infected cats. Macrophages in the lung and spleen of infected cats contained parasitized erythrocytes, either with or without inclusions. Some macrophages contained erythrocyte-free organisms in phagocytic vacuoles."}
{"id": "PMID:207854", "title": "Effect of concomitant administration of magnesium trisilicate on GI absorption of dexamethasone in humans.", "content": "The oral absorption of dexamethasone in humans was compared to its absorption when coadministered with magnesium trisilicate. The bioavailability of dexamethasone was estimated by measuring the suppressive effect of the drug on the daily excretion of endogenous steroids. Administration of 1 mg of dexamethasone to six healthy male volunteers significantly decreased the urinary excretion of 11-hydroxycorticosteroids. However, the coadministration of magnesium trisilicate with dexamethasone decreased its absorption, as indicated by the increased urinary excretion of 11-hydroxycorticosteroids. The decrease in absorption was attributed to drug adsorption on the antacid surface. These results confirm previous in vitro findings.", "contents": "Effect of concomitant administration of magnesium trisilicate on GI absorption of dexamethasone in humans. The oral absorption of dexamethasone in humans was compared to its absorption when coadministered with magnesium trisilicate. The bioavailability of dexamethasone was estimated by measuring the suppressive effect of the drug on the daily excretion of endogenous steroids. Administration of 1 mg of dexamethasone to six healthy male volunteers significantly decreased the urinary excretion of 11-hydroxycorticosteroids. However, the coadministration of magnesium trisilicate with dexamethasone decreased its absorption, as indicated by the increased urinary excretion of 11-hydroxycorticosteroids. The decrease in absorption was attributed to drug adsorption on the antacid surface. These results confirm previous in vitro findings."}
{"id": "PMID:207855", "title": "Synthesis and quantitative structure-activity relationships of antibacterial 1-(substituted benzhydryl)-4-(5-nitro-2-furfurylideneamino) piperazines.", "content": "1-Benzhydryl -4- (5-nitro-2-furfurylideneamino) piperazine and 11 substituted analogs were prepared and examined for in vitro antimicrobial activity. The compounds were active against Bacillus cereus 7, Bacillus megaterium 122, Bacillus subtilis 104, Clostridium perfringens 13, and the tetracycline-resistant Clostridium perfringens 37. Regression analyses on the antibacterial activity data based on the Hansch approach, using pi, pi2, and sigma parameters, yielded several statistically significant correlation equations. 1-Benzhydryl-4-(5-nitro-2-furfurylideneamino) piperazine stopped the protein and DNA syntheses in C. perfringens 13, as indicated by precipitable radioactivity. The compound, however, showed no effect on the cell wall synthesis in the bacteria.", "contents": "Synthesis and quantitative structure-activity relationships of antibacterial 1-(substituted benzhydryl)-4-(5-nitro-2-furfurylideneamino) piperazines. 1-Benzhydryl -4- (5-nitro-2-furfurylideneamino) piperazine and 11 substituted analogs were prepared and examined for in vitro antimicrobial activity. The compounds were active against Bacillus cereus 7, Bacillus megaterium 122, Bacillus subtilis 104, Clostridium perfringens 13, and the tetracycline-resistant Clostridium perfringens 37. Regression analyses on the antibacterial activity data based on the Hansch approach, using pi, pi2, and sigma parameters, yielded several statistically significant correlation equations. 1-Benzhydryl-4-(5-nitro-2-furfurylideneamino) piperazine stopped the protein and DNA syntheses in C. perfringens 13, as indicated by precipitable radioactivity. The compound, however, showed no effect on the cell wall synthesis in the bacteria."}
{"id": "PMID:207856", "title": "New opiate-receptor model.", "content": "A new opiate-receptor model is proposed in which only one conformation of the receptor is needed for binding of both agonists and antagonists. There are two different spacially fixed amine-binding sites in this model: one agonist and one antagonist. The opiates undergo binding to their amine-binding sites via the lone electron pair on nitrogen. The role of the N-allyl or other such group in imparting antagonist properties is explained in terms of the steric requirements of this group. For this group to be accommodated without imposing severe steric interactions in the rest of the opiate molecule, the piperidine ring must assume a flexible (skew boat) conformation; in this conformation, the N-lone-pair electron lobe assumes the characteristic directionality of an antagonist toward its amine-binding site. If the N-lone-pair lobe is not rigorously maintained in this direction, the opiate molecule assumes both antagonist and agonist conformations and mixed antagonist-agonist activity is observed. The observed differences in the effect of sodium on the degree of binding of an agonist versus an antagonist can be explained in this model by the different effects of sodium on the two amine-binding sites. The antagonist activity of an N-methyl antagonist can be rationalized on the basis of the proposed model.", "contents": "New opiate-receptor model. A new opiate-receptor model is proposed in which only one conformation of the receptor is needed for binding of both agonists and antagonists. There are two different spacially fixed amine-binding sites in this model: one agonist and one antagonist. The opiates undergo binding to their amine-binding sites via the lone electron pair on nitrogen. The role of the N-allyl or other such group in imparting antagonist properties is explained in terms of the steric requirements of this group. For this group to be accommodated without imposing severe steric interactions in the rest of the opiate molecule, the piperidine ring must assume a flexible (skew boat) conformation; in this conformation, the N-lone-pair electron lobe assumes the characteristic directionality of an antagonist toward its amine-binding site. If the N-lone-pair lobe is not rigorously maintained in this direction, the opiate molecule assumes both antagonist and agonist conformations and mixed antagonist-agonist activity is observed. The observed differences in the effect of sodium on the degree of binding of an agonist versus an antagonist can be explained in this model by the different effects of sodium on the two amine-binding sites. The antagonist activity of an N-methyl antagonist can be rationalized on the basis of the proposed model."}
{"id": "PMID:207857", "title": "Comparison of the mechanism of isoproterenol-stimulated glycogenolysis in skeletal muscle of normal and phosphorylase kinase-deficient mice (I strain).", "content": "Diaphragm extracts from mice with the phosphorylase kinase deficiency mutation (I strain) have only 3.7% of the phosphorylase kinase activity of muscle extracts of the control strain (C57BL). Nevertheless, previous studies have shown that isoproterenol-stimulated glycogenolysis in I strain diaphragm muscle at a rate 57% (average relative response at 10 isoproterenol concentrations) of that of C57BL (GROSS, S.R., MAYER, S.E. and LONGSHORE, M.A.: J. Pharmacol. Exp. Ther. 198: 523-538, 1976). The present studies were initiated to compare the mechanism of isoproterenol-stimulated glycogenolysis in I and C57BL diaphragms. Isoproterenol was found to stimulate phosphorylase b to a conversion with an EC50 of 8 nM in muscles from mice of either strain, and the maximum increase in phosphorylase alpha activity in I diaphragms was 23% of that in C57BL diaphragms. Moreover, the initial rate of increase in phosphorylase alpha activity in I diaphragms incubated with 40 nM isoproterenol was 24% of that in C57BL muscles. The isoproterenol-stimulated increases in cyclic AMP content in diaphragms of the two strains were the same. Incubation of I diaphragms with isoproterenol did not significantly increase the concentrations of AMP, IMP or inorganic phosphate, activators of phosphorylase beta activity, nor was there a decrease in ATP and glucose 6-phosphate content, allosteric inhibitors of phosphorylase beta activity. Thus, phosphorylase alpha formation is the principal, if not only, catalyst of isoproterenol-stimulated glycogenolysis in skeletal muscle of phosphorylase kinase-deficient mice, and no evidence was obtained indicating that allosteric regulation of phosphorylase beta activity is part of the mechanism.", "contents": "Comparison of the mechanism of isoproterenol-stimulated glycogenolysis in skeletal muscle of normal and phosphorylase kinase-deficient mice (I strain). Diaphragm extracts from mice with the phosphorylase kinase deficiency mutation (I strain) have only 3.7% of the phosphorylase kinase activity of muscle extracts of the control strain (C57BL). Nevertheless, previous studies have shown that isoproterenol-stimulated glycogenolysis in I strain diaphragm muscle at a rate 57% (average relative response at 10 isoproterenol concentrations) of that of C57BL (GROSS, S.R., MAYER, S.E. and LONGSHORE, M.A.: J. Pharmacol. Exp. Ther. 198: 523-538, 1976). The present studies were initiated to compare the mechanism of isoproterenol-stimulated glycogenolysis in I and C57BL diaphragms. Isoproterenol was found to stimulate phosphorylase b to a conversion with an EC50 of 8 nM in muscles from mice of either strain, and the maximum increase in phosphorylase alpha activity in I diaphragms was 23% of that in C57BL diaphragms. Moreover, the initial rate of increase in phosphorylase alpha activity in I diaphragms incubated with 40 nM isoproterenol was 24% of that in C57BL muscles. The isoproterenol-stimulated increases in cyclic AMP content in diaphragms of the two strains were the same. Incubation of I diaphragms with isoproterenol did not significantly increase the concentrations of AMP, IMP or inorganic phosphate, activators of phosphorylase beta activity, nor was there a decrease in ATP and glucose 6-phosphate content, allosteric inhibitors of phosphorylase beta activity. Thus, phosphorylase alpha formation is the principal, if not only, catalyst of isoproterenol-stimulated glycogenolysis in skeletal muscle of phosphorylase kinase-deficient mice, and no evidence was obtained indicating that allosteric regulation of phosphorylase beta activity is part of the mechanism."}
{"id": "PMID:207859", "title": "Genetic control of opiate-induced locomotor activity in mice.", "content": "Swiss-Webster stock male and female mice were tested for running activity after a 20 mg/kg dose of levorphanol. The best runners and worst runners were then bred. Within each litter, brother-sister pairs with the highest and lowest running activity after a test dose of levorphanol (20 mg/kg) were segregated and bred. This procedure was followed to the F4 generation. Running activity, analgesia and brain catecholamines were studied. The results showed that the \"non-running\" (NR) trait segregated at the F1 generation, while the \"running\" (R) trait diverged more slowly. However, by the third generation, the R mice differed significantly from the F0 stock mice. NR mice also did not show locomotor activity when tested with amphetamine. While the NR mice showed reduced running response to levorphanol they were significantly more sensitive than the F0 stock to the analgesic effect. Measurement of brain catecholamines showed no difference between R and NR mice in dopamine or serotonin, but did show a significant increase in norepinephrine in the NR strain.", "contents": "Genetic control of opiate-induced locomotor activity in mice. Swiss-Webster stock male and female mice were tested for running activity after a 20 mg/kg dose of levorphanol. The best runners and worst runners were then bred. Within each litter, brother-sister pairs with the highest and lowest running activity after a test dose of levorphanol (20 mg/kg) were segregated and bred. This procedure was followed to the F4 generation. Running activity, analgesia and brain catecholamines were studied. The results showed that the \"non-running\" (NR) trait segregated at the F1 generation, while the \"running\" (R) trait diverged more slowly. However, by the third generation, the R mice differed significantly from the F0 stock mice. NR mice also did not show locomotor activity when tested with amphetamine. While the NR mice showed reduced running response to levorphanol they were significantly more sensitive than the F0 stock to the analgesic effect. Measurement of brain catecholamines showed no difference between R and NR mice in dopamine or serotonin, but did show a significant increase in norepinephrine in the NR strain."}
{"id": "PMID:207866", "title": "A behavioral approach to physical rehabilitation: a case study.", "content": "This report presents an application of a behavioral approach used in treatment of a 65-year-old multiple handicapped woman admitted to a 29-bed physical rehabilitation hospital unit. Measurement used was a combined multiple baseline and BABA design. Findings can be summarized as follows: 1) Inappropriate behavior decreased during treatment, i.e., call outs and appropriate behavior increased, time spent out of bed, adhering to her diet, and wearing of a back brace; 2) Treatment quickly generalized to other behaviors;3) Follow-up measures at 6 and 18 months showed continued improvement.", "contents": "A behavioral approach to physical rehabilitation: a case study. This report presents an application of a behavioral approach used in treatment of a 65-year-old multiple handicapped woman admitted to a 29-bed physical rehabilitation hospital unit. Measurement used was a combined multiple baseline and BABA design. Findings can be summarized as follows: 1) Inappropriate behavior decreased during treatment, i.e., call outs and appropriate behavior increased, time spent out of bed, adhering to her diet, and wearing of a back brace; 2) Treatment quickly generalized to other behaviors;3) Follow-up measures at 6 and 18 months showed continued improvement."}
{"id": "PMID:207868", "title": "Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl- and N-tert-alkylnormorphines.", "content": "A series of N-sec- and N-tert-alkylnormorphines was synthesized and evaluated for analgesic potency, antagonist activity, and opiate receptor binding. Computer-assisted conformational analysis profiles were utilized to assist in the selection of compounds for synthesis and correlation of receptor events with in vivo observations. N-tert-Alkylnormorphines 5a-c were devoid of agonist activity; however, some sec-alkyl analogues showed interesting mixed agonist-antagnoist actions. N-sec-Butyl- and N-(alpha-methylally)normorphine were separated into R and S isomers, which exhibited quantitative pharmacological differences. The N-sec-butyl S isomer 10a showed analgesia approximating morphine with nalorphine-like antagonist activity. Preliminary testing indicates only slight evidence for physical dependence with this compound.", "contents": "Analgesics. 1. Synthesis and analgesic properties of N-sec-alkyl- and N-tert-alkylnormorphines. A series of N-sec- and N-tert-alkylnormorphines was synthesized and evaluated for analgesic potency, antagonist activity, and opiate receptor binding. Computer-assisted conformational analysis profiles were utilized to assist in the selection of compounds for synthesis and correlation of receptor events with in vivo observations. N-tert-Alkylnormorphines 5a-c were devoid of agonist activity; however, some sec-alkyl analogues showed interesting mixed agonist-antagnoist actions. N-sec-Butyl- and N-(alpha-methylally)normorphine were separated into R and S isomers, which exhibited quantitative pharmacological differences. The N-sec-butyl S isomer 10a showed analgesia approximating morphine with nalorphine-like antagonist activity. Preliminary testing indicates only slight evidence for physical dependence with this compound."}
{"id": "PMID:207869", "title": "Post-menopausal vaginitis.", "content": "The organisms cultured from the vaginal swabs of 383 women over 50 years old with vaginal discharge were compared with those from 148 normal women of similar age attending a cytology clinic. The only significant difference was that yeasts were found in 20% and 6% of the two groups of women, respectively. It is therefore concluded that in post-menopausal women with vaginal discharge, the main microbiological requirement is for the diagnosis and treatment of yeast infection.", "contents": "Post-menopausal vaginitis. The organisms cultured from the vaginal swabs of 383 women over 50 years old with vaginal discharge were compared with those from 148 normal women of similar age attending a cytology clinic. The only significant difference was that yeasts were found in 20% and 6% of the two groups of women, respectively. It is therefore concluded that in post-menopausal women with vaginal discharge, the main microbiological requirement is for the diagnosis and treatment of yeast infection."}
{"id": "PMID:207870", "title": "Microviscosity of mucosal cellular membranes in toad urinary bladder: relation to antidiuretic hormone action on water permeability.", "content": "The microviscosity of cellular membranes (or membrane fluidity) was measured in suspensions of single mucosal cells isolated from the urinary bladder of the toad, Bufo marinus, by the technique of polarized fluorescence emission spectroscopy utilizing the hydrophobic fluorescent probe, perylene. At 23 degrees C, 5 mM dibutyryl cyclic 3',5'-AMP decreased the apparent microviscosity of the cell membranes from 3.31 to 3.07 P, a minimum decrease of 7.3% (P less than 0.001) with a physiological time course. Direct visualization of the cell suspension indicated that 98% of the cells were viable, as indicated by Trypan Blue dye exclusion. The fluorescent perylene could be seen only in plasma membranes, suggesting that the measured viscosity was that of plasma membrane with little contribution from the membranes of cellular organelles. Addition of antidiuretic hormone to intact hemibladders stained with perylene produced changes in fluorescence consistent with a similar 7% decrease in apparent microviscosity with a physiological time course. However, finite interpretation of the findings in intact tissue cannot be made because the location and the fluorescent lifetime of the probe could only be conducted on the isolated cells. Comparison with previously determined relationships between water permeability and microviscosity in artificial bilayers suggests that the 7% (a lower limit) decrease in microviscosity would produce only a 6.5% increase in water permeability.", "contents": "Microviscosity of mucosal cellular membranes in toad urinary bladder: relation to antidiuretic hormone action on water permeability. The microviscosity of cellular membranes (or membrane fluidity) was measured in suspensions of single mucosal cells isolated from the urinary bladder of the toad, Bufo marinus, by the technique of polarized fluorescence emission spectroscopy utilizing the hydrophobic fluorescent probe, perylene. At 23 degrees C, 5 mM dibutyryl cyclic 3',5'-AMP decreased the apparent microviscosity of the cell membranes from 3.31 to 3.07 P, a minimum decrease of 7.3% (P less than 0.001) with a physiological time course. Direct visualization of the cell suspension indicated that 98% of the cells were viable, as indicated by Trypan Blue dye exclusion. The fluorescent perylene could be seen only in plasma membranes, suggesting that the measured viscosity was that of plasma membrane with little contribution from the membranes of cellular organelles. Addition of antidiuretic hormone to intact hemibladders stained with perylene produced changes in fluorescence consistent with a similar 7% decrease in apparent microviscosity with a physiological time course. However, finite interpretation of the findings in intact tissue cannot be made because the location and the fluorescent lifetime of the probe could only be conducted on the isolated cells. Comparison with previously determined relationships between water permeability and microviscosity in artificial bilayers suggests that the 7% (a lower limit) decrease in microviscosity would produce only a 6.5% increase in water permeability."}
{"id": "PMID:207871", "title": "Evidence for involvement of microtubules in the action of vasopressin in toad urinary bladder. I. Functional studies on the effects of antimitotic agents on the response to vasopressin.", "content": "The antimitotic agents colchicine, podophyllotoxin, and vinblastine inhibit the action of vasopressin and cyclic AMP on osmotic water movement in the toad urinary bladder. The alkaloids have no effect on either basal or vasopressin-stimulated sodium transport or urea flux across the tissue. Inhibition of vasopressin-induced water movement is half-maximal at the following alkaloid concentrations: colchicine, 1.8 X 10(-6) M; podophyllotoxin, 5 X 10(-7)M; and vinblastine, 1 X 10(-7)M. The characteristics of the specificity, time-dependence and temperature-dependence of the inhibitory effect of colchicine are similar to the characteristics of the interaction of this drug with tubulin in vitro, and they differ from those of its effect on nucleoside transport. Inhibition of the vasopressin response by colchicine, podophyllotoxin, and vinblastine is not readily reversed. The findings support the view that the inhibition of vasopressin-induced water movement by the antimitotic agents is due to the interaction of these agents with tubulin and consequent interference with microtubule integrity and function. Taken together with the results of biochemical and morphological studies, the findings provide evidence that cytoplasmic microtubules play a critical role in the action of vasopressin on transcellular water movement in the toad bladder.", "contents": "Evidence for involvement of microtubules in the action of vasopressin in toad urinary bladder. I. Functional studies on the effects of antimitotic agents on the response to vasopressin. The antimitotic agents colchicine, podophyllotoxin, and vinblastine inhibit the action of vasopressin and cyclic AMP on osmotic water movement in the toad urinary bladder. The alkaloids have no effect on either basal or vasopressin-stimulated sodium transport or urea flux across the tissue. Inhibition of vasopressin-induced water movement is half-maximal at the following alkaloid concentrations: colchicine, 1.8 X 10(-6) M; podophyllotoxin, 5 X 10(-7)M; and vinblastine, 1 X 10(-7)M. The characteristics of the specificity, time-dependence and temperature-dependence of the inhibitory effect of colchicine are similar to the characteristics of the interaction of this drug with tubulin in vitro, and they differ from those of its effect on nucleoside transport. Inhibition of the vasopressin response by colchicine, podophyllotoxin, and vinblastine is not readily reversed. The findings support the view that the inhibition of vasopressin-induced water movement by the antimitotic agents is due to the interaction of these agents with tubulin and consequent interference with microtubule integrity and function. Taken together with the results of biochemical and morphological studies, the findings provide evidence that cytoplasmic microtubules play a critical role in the action of vasopressin on transcellular water movement in the toad bladder."}
{"id": "PMID:207876", "title": "Formation of P1, P2-dinucleoside 5'-pyrophosphates under potentially prebiological conditions.", "content": "Organic pyrophosphates such as UppA and NAD are formed when a solution containing a nucleotide, a nucleoside 5'-polyphosphate, Mg2+ and imidazole are allowed to dry out. We suggest that this synthesis may have occured concurrently with oligonucleotide formation.", "contents": "Formation of P1, P2-dinucleoside 5'-pyrophosphates under potentially prebiological conditions. Organic pyrophosphates such as UppA and NAD are formed when a solution containing a nucleotide, a nucleoside 5'-polyphosphate, Mg2+ and imidazole are allowed to dry out. We suggest that this synthesis may have occured concurrently with oligonucleotide formation."}
{"id": "PMID:207877", "title": "Evolutionary change in invertebrate cytochrome C.", "content": "Recently published amino acid sequences are compared to those of other cytochromes c. Molecular phylogenies constructed by using an ancestral sequence method are compared to the classical biological view of invertebrate evolution. Problems associated with the analysis of sequences of different chain lengths and of high variability are discussed, and the logistics of increasing the representation of key invertebrate phyla is assessed.", "contents": "Evolutionary change in invertebrate cytochrome C. Recently published amino acid sequences are compared to those of other cytochromes c. Molecular phylogenies constructed by using an ancestral sequence method are compared to the classical biological view of invertebrate evolution. Problems associated with the analysis of sequences of different chain lengths and of high variability are discussed, and the logistics of increasing the representation of key invertebrate phyla is assessed."}
{"id": "PMID:207878", "title": "Parallel evolution of pairs of dehydrogenase isoenzymes.", "content": "Lactate dehydrogenase and glycerol 3-phosphate dehydrogenase are metabolically coupled by the anaerobic dismutation of glyceraldehyde 3-phosphate and by the NAD redox state. This causes the concentrations of lactate and glycerol 3-phosphate to accumulate proportionally during anaerobic muscle contraction; these concentrations are high relative to those in aerobic tissues such as liver. We show that the isoenzymes of lactate dehydrogenase and glycerol 3-phosphate dehydrogenase from chicken breast muscle have Km values for lactate and glycerol 3-phosphate, respectively, that are 10-fold higher than the Km values measured for the lactate dehydrogenase and glycerol 3-phosphate dehydrogenase isoenzymes from chicken liver. The association of proportionally higher Km values with the potential for proportionally higher accumulation of substrates suggests that the isoenzymes of lactate dehydrogenase and glycerol 3-phosphate dehydrogenase from chicken muscle have evolved in parallel as a coupled metabolic unit distinct from the coupled isoenzymes in liver. The parallelism observed for the reduced substrates extends to the oxidized substrates, and to the coenzymes, NAD+ and NADH.", "contents": "Parallel evolution of pairs of dehydrogenase isoenzymes. Lactate dehydrogenase and glycerol 3-phosphate dehydrogenase are metabolically coupled by the anaerobic dismutation of glyceraldehyde 3-phosphate and by the NAD redox state. This causes the concentrations of lactate and glycerol 3-phosphate to accumulate proportionally during anaerobic muscle contraction; these concentrations are high relative to those in aerobic tissues such as liver. We show that the isoenzymes of lactate dehydrogenase and glycerol 3-phosphate dehydrogenase from chicken breast muscle have Km values for lactate and glycerol 3-phosphate, respectively, that are 10-fold higher than the Km values measured for the lactate dehydrogenase and glycerol 3-phosphate dehydrogenase isoenzymes from chicken liver. The association of proportionally higher Km values with the potential for proportionally higher accumulation of substrates suggests that the isoenzymes of lactate dehydrogenase and glycerol 3-phosphate dehydrogenase from chicken muscle have evolved in parallel as a coupled metabolic unit distinct from the coupled isoenzymes in liver. The parallelism observed for the reduced substrates extends to the oxidized substrates, and to the coenzymes, NAD+ and NADH."}
{"id": "PMID:207879", "title": "Mechanism of steroid binding to serum proteins.", "content": "Association and dissociation rate constants of steroid complexes with progesterone-binding globulin (PBG) and with corticosteroid-binding globulin have been determined, utilizing the fluorescence quenching phenomenon observed on steroid binding to protein. Stopped-flow techniques were used in most cases. The dissociation rates of the complexes with steroid-binding proteins of serum are much greater than those of steroid-receptor complexes, in accordance with the biological functions of these two types of proteins. Association of steroids with PBG is accompanied by conformational changes in both components of the complexes. Chemical modification of tryptophan, lysine, and tyrosine in PBG results in inactivation of the binding site; complex formation with progesterone protects against this inactivation. A comparison of the affinity constants of PBG complexes with steroids of different structures leads to a conceptual image of the binding site and to localization of the various forces of interaction over the binding site area.", "contents": "Mechanism of steroid binding to serum proteins. Association and dissociation rate constants of steroid complexes with progesterone-binding globulin (PBG) and with corticosteroid-binding globulin have been determined, utilizing the fluorescence quenching phenomenon observed on steroid binding to protein. Stopped-flow techniques were used in most cases. The dissociation rates of the complexes with steroid-binding proteins of serum are much greater than those of steroid-receptor complexes, in accordance with the biological functions of these two types of proteins. Association of steroids with PBG is accompanied by conformational changes in both components of the complexes. Chemical modification of tryptophan, lysine, and tyrosine in PBG results in inactivation of the binding site; complex formation with progesterone protects against this inactivation. A comparison of the affinity constants of PBG complexes with steroids of different structures leads to a conceptual image of the binding site and to localization of the various forces of interaction over the binding site area."}
{"id": "PMID:207883", "title": "Alkaline DNase activity in cells infected with a temperature-sensitive mutant of herpes simplex virus type 2.", "content": "BHK cells infected with the temperature-sensitive mutant ts13 of herpes simplex virus type 2 at a nonpermissive temperature lack the alkaline nuclease activity, which is induced by the mutant at a permissive temperature and by wild-type virus at either temperature. For ts13, enzyme activity could be induced by a temperature shift to permissive conditions, but not in the presence of cycloheximide. After a shift from permissive to nonpermissive conditions in the presence of cycloheximide, the activity was stable in wild-type, but not in mutant-infected, cells. After extensive purification, the wild-type nuclease was fourfold more heat stable in the presence of substrate than was the mutant enzyme. Mixtures of both purified enzymes showed the predicted intermediate stabilities. The results strongly suggest that the enzyme is virus coded and that the mutant possesses a lesion in the structural gene of the enzyme.", "contents": "Alkaline DNase activity in cells infected with a temperature-sensitive mutant of herpes simplex virus type 2. BHK cells infected with the temperature-sensitive mutant ts13 of herpes simplex virus type 2 at a nonpermissive temperature lack the alkaline nuclease activity, which is induced by the mutant at a permissive temperature and by wild-type virus at either temperature. For ts13, enzyme activity could be induced by a temperature shift to permissive conditions, but not in the presence of cycloheximide. After a shift from permissive to nonpermissive conditions in the presence of cycloheximide, the activity was stable in wild-type, but not in mutant-infected, cells. After extensive purification, the wild-type nuclease was fourfold more heat stable in the presence of substrate than was the mutant enzyme. Mixtures of both purified enzymes showed the predicted intermediate stabilities. The results strongly suggest that the enzyme is virus coded and that the mutant possesses a lesion in the structural gene of the enzyme."}
{"id": "PMID:207880", "title": "Nonsteroidal antiestrogens: their biological effects and potential mechanisms of action.", "content": "The uterotropic and antiuterotrapic effects of a variety of structural derivatives of the nonsteroidal antiestrogen tamoxifen have been determined in the rat and the mouse. One derivative, monohydroxytamoxifen, was found to be a potent antiestrogen in the rat, with a high affinity for the estrogen receptor. Various techniques of sucrose density gradient analysis were used to demonstrate that estradiol and tamoxifen bind to the rat uterine cytoplasmic estrogen receptor. Estrogens and antiestrogens provoke the translocation of estrogen receptors to the nucleus and deplete the cytoplasmic estrogen receptor pool for short or long periods depending on the dose administered. Estradiol stimulates endometrial hyperplasia with an increase in total uterine DNA content, whereas tamoxifen stimulates endometrial hypertrophy with only a slight increase in uterine DNA content. It is concluded that the molecular shape of the ligand that binds to the estrogen receptor determines antiestrogenic activity.", "contents": "Nonsteroidal antiestrogens: their biological effects and potential mechanisms of action. The uterotropic and antiuterotrapic effects of a variety of structural derivatives of the nonsteroidal antiestrogen tamoxifen have been determined in the rat and the mouse. One derivative, monohydroxytamoxifen, was found to be a potent antiestrogen in the rat, with a high affinity for the estrogen receptor. Various techniques of sucrose density gradient analysis were used to demonstrate that estradiol and tamoxifen bind to the rat uterine cytoplasmic estrogen receptor. Estrogens and antiestrogens provoke the translocation of estrogen receptors to the nucleus and deplete the cytoplasmic estrogen receptor pool for short or long periods depending on the dose administered. Estradiol stimulates endometrial hyperplasia with an increase in total uterine DNA content, whereas tamoxifen stimulates endometrial hypertrophy with only a slight increase in uterine DNA content. It is concluded that the molecular shape of the ligand that binds to the estrogen receptor determines antiestrogenic activity."}
{"id": "PMID:207884", "title": "Presence of 5'-terminal cap structures in virus-specific RNA from feline leukemia virus-infected cells.", "content": "The F-422 line of feline thymus tumor cells, chronically infected with the Rickard strain of feline leukemia virus (R-FeLV), was labeled with 32P, and the total cytoplasmic RNA was isolated. The RNA was centrifuged through sucrose gradients, and R-FeLV virus-specific RNA (vRNA) was located by hybridization of portions of the gradient fractions to R-FeLV complementary DNA. vRNA classes with average sedimentation coefficients of approximately 36S, 28S, 23S, and 15S were identified. Each class of RNA was recovered by hybridized with mercurated R-FeLV complementary DNA, and the hybrids were chromatographed on columns of sulfhydryl-Sepharose to separate them from unhybridized cellular RNA. Although insufficient amount of 36S and 28S vRNA were obtained for further analysis, the 23S and 15S VRNA classes were analyzed to determine the nature of their 5' termini. Each of these vRNA classes was found to contain stoichiometric amounts of cap structures per unit length of RNA, consistent with the presence of one cap per molecule. The structure of the 23S vRNA cap was found to be m7G5'ppp5'GmpAp, whereas that of the 15S vRNA cap was m7G5'ppp5'GmpGp.", "contents": "Presence of 5'-terminal cap structures in virus-specific RNA from feline leukemia virus-infected cells. The F-422 line of feline thymus tumor cells, chronically infected with the Rickard strain of feline leukemia virus (R-FeLV), was labeled with 32P, and the total cytoplasmic RNA was isolated. The RNA was centrifuged through sucrose gradients, and R-FeLV virus-specific RNA (vRNA) was located by hybridization of portions of the gradient fractions to R-FeLV complementary DNA. vRNA classes with average sedimentation coefficients of approximately 36S, 28S, 23S, and 15S were identified. Each class of RNA was recovered by hybridized with mercurated R-FeLV complementary DNA, and the hybrids were chromatographed on columns of sulfhydryl-Sepharose to separate them from unhybridized cellular RNA. Although insufficient amount of 36S and 28S vRNA were obtained for further analysis, the 23S and 15S VRNA classes were analyzed to determine the nature of their 5' termini. Each of these vRNA classes was found to contain stoichiometric amounts of cap structures per unit length of RNA, consistent with the presence of one cap per molecule. The structure of the 23S vRNA cap was found to be m7G5'ppp5'GmpAp, whereas that of the 15S vRNA cap was m7G5'ppp5'GmpGp."}
{"id": "PMID:207881", "title": "Hormonal regulation of cultured rabbit endometrial cells.", "content": "A technique for culturing primary explants of rabbit endometrial cells in chemically defined medium has been developed. Diethylstilbestrol and natural estrogens were found to increase the rate of DNA initiation while progesterone had the opposite effect. Ultrastructural studies revealed that with estrogens, the cultures had the appearance of rapidly dividing cells having large euchromatic nuclei and prominent nucleoli, with aboundant free ribosomes in the cytoplasm. On the other hand, progesterone induced the formation of large multinucleated cells and also converted the cells to a more secretory type. When the cultures appear secretory, a protein called blastokinin (uteroglobin) is believed secreted. We have found that cultured cells synthesize blastokinin and progesterone is necessary for its continuous synthesis. The cultures were found to have receptors for the ovarian hormones and these receptors exhibited saturation kinetics. The dissociation constants for the receptors were also determined. A hypothetical model for the hormonal regulation of cell proliferation and differentiation is proposed.", "contents": "Hormonal regulation of cultured rabbit endometrial cells. A technique for culturing primary explants of rabbit endometrial cells in chemically defined medium has been developed. Diethylstilbestrol and natural estrogens were found to increase the rate of DNA initiation while progesterone had the opposite effect. Ultrastructural studies revealed that with estrogens, the cultures had the appearance of rapidly dividing cells having large euchromatic nuclei and prominent nucleoli, with aboundant free ribosomes in the cytoplasm. On the other hand, progesterone induced the formation of large multinucleated cells and also converted the cells to a more secretory type. When the cultures appear secretory, a protein called blastokinin (uteroglobin) is believed secreted. We have found that cultured cells synthesize blastokinin and progesterone is necessary for its continuous synthesis. The cultures were found to have receptors for the ovarian hormones and these receptors exhibited saturation kinetics. The dissociation constants for the receptors were also determined. A hypothetical model for the hormonal regulation of cell proliferation and differentiation is proposed."}
{"id": "PMID:207885", "title": "RNA of mouse hepatitis virus.", "content": "The RNA of mouse hepatitis virus, a coronavirus, was isolated from the virus released early in the infection and analyzed by sucrose gradient sedimentation and electrophoresis. It was found to consist of a piece of single-stranded RNA of about 60S. Its molecular weight was estimated to be 5.4 X 10(6) by electrophoresis in methylmercury-agarose gels. At least one third of the RNA contained polyadenylated sequences. It is, therefore, probably positive stranded. The virus harvested late in the infection contained, in addition to 60S, some 30 to 50S RNA that are possibly degradation products of the 60S RNA. No difference in the electrophoretic behavior could be detected between the RNA isolated from a pathogenic (JHM) and a nonpathogenic (A59) strain.", "contents": "RNA of mouse hepatitis virus. The RNA of mouse hepatitis virus, a coronavirus, was isolated from the virus released early in the infection and analyzed by sucrose gradient sedimentation and electrophoresis. It was found to consist of a piece of single-stranded RNA of about 60S. Its molecular weight was estimated to be 5.4 X 10(6) by electrophoresis in methylmercury-agarose gels. At least one third of the RNA contained polyadenylated sequences. It is, therefore, probably positive stranded. The virus harvested late in the infection contained, in addition to 60S, some 30 to 50S RNA that are possibly degradation products of the 60S RNA. No difference in the electrophoretic behavior could be detected between the RNA isolated from a pathogenic (JHM) and a nonpathogenic (A59) strain."}
{"id": "PMID:207882", "title": "Mouse mammary tumor virus genes: regulation of expression by glucocorticoids and structural analysis with restriction endonucleases.", "content": "The production of mouse mammary tumor virus (MTV) is stimulated by treatment of mammary carcinoma cells with glucocorticoid hormones (e.g., dexamethasone). The reaction appears to be a primary and receptor-mediated phenomenon in which the rate of synthesis of MTV RNA is selectively increased; the maximally induced rate is reached within 15 min after addition of the hormone. Production of MTV RNA is also stimulated by dexamethasone in some but not all clonal isolates of nonmurine cells infected by the virus. Using restriction endonucleases, we have characterized both integrated and unintegrated viral DNA from clones of infected rat hepatoma (HTC) cells. We suggest that the site(s) in the rat cell genome into which MTV DNA integrates may be a determining factor for MTV RNA synthesis.", "contents": "Mouse mammary tumor virus genes: regulation of expression by glucocorticoids and structural analysis with restriction endonucleases. The production of mouse mammary tumor virus (MTV) is stimulated by treatment of mammary carcinoma cells with glucocorticoid hormones (e.g., dexamethasone). The reaction appears to be a primary and receptor-mediated phenomenon in which the rate of synthesis of MTV RNA is selectively increased; the maximally induced rate is reached within 15 min after addition of the hormone. Production of MTV RNA is also stimulated by dexamethasone in some but not all clonal isolates of nonmurine cells infected by the virus. Using restriction endonucleases, we have characterized both integrated and unintegrated viral DNA from clones of infected rat hepatoma (HTC) cells. We suggest that the site(s) in the rat cell genome into which MTV DNA integrates may be a determining factor for MTV RNA synthesis."}
{"id": "PMID:207886", "title": "Purification and characterization of varicella-zoster virus-induced DNA polymerase.", "content": "Infection of WI-38 human fibroblasts with varicella-zoster virus led to the stimulation of host cell DNA polymerase synthesis and induction of a new virus-specific DNA polymerase. This virus-induced DNA polymerase was partially purified and separated from host cell enzymes by DEAE-cellulose and phosphocellulose column chromatographies. This virus-induced enzyme could be distinguished from host cell enzyme by its chromatographic behavior, template specificity, and its requirement of salt for maximal activity. The enzyme could efficiently use poly(dC).oligo(dG)12-18 as well as poly(dA).oligo(dT)12-18 as template-primers. It required Mg2+ for maximal polymerization activity and was sensitive to phosphonoacetic acid, to which host alpha- and beta-DNA polymerase were relatively resistant. In addition, this induced DNA polymerase activity was enhanced by adding 60 mM (NH4)2SO4 to the reaction mixture.", "contents": "Purification and characterization of varicella-zoster virus-induced DNA polymerase. Infection of WI-38 human fibroblasts with varicella-zoster virus led to the stimulation of host cell DNA polymerase synthesis and induction of a new virus-specific DNA polymerase. This virus-induced DNA polymerase was partially purified and separated from host cell enzymes by DEAE-cellulose and phosphocellulose column chromatographies. This virus-induced enzyme could be distinguished from host cell enzyme by its chromatographic behavior, template specificity, and its requirement of salt for maximal activity. The enzyme could efficiently use poly(dC).oligo(dG)12-18 as well as poly(dA).oligo(dT)12-18 as template-primers. It required Mg2+ for maximal polymerization activity and was sensitive to phosphonoacetic acid, to which host alpha- and beta-DNA polymerase were relatively resistant. In addition, this induced DNA polymerase activity was enhanced by adding 60 mM (NH4)2SO4 to the reaction mixture."}
{"id": "PMID:207887", "title": "Rescue of endogenous 30S retroviral sequences from mouse cells by baboon type C virus.", "content": "Mus musculus SC-1 cells were infected with M7 baboon type C virus. The progeny of this infection included viral pseudotypes that contained M7 helper virus and endogenous 30S retrovirus-associated sequences derived from SC-1 cells (RAS). The RAS sequences are unrelated by nucleic acid hybridization criteria to previously described types of murine retroviruses and do not code for known murine viral structural proteins. The RAS genome is present in multiple copies in the DNA of laboratory (M. musculus) and Asian (M. caroli and M. cervicolor) mice, is expressed in the RNA of uninfected mouse cells, and can be efficiently rescued by type C, but not type B, viruses. RAS is closely related to 30S virus-associated RNA in NIH/3T3 and BALB/c JLSV-9 cells and may be analogous to the defective 30S RNA sequences found in rats.", "contents": "Rescue of endogenous 30S retroviral sequences from mouse cells by baboon type C virus. Mus musculus SC-1 cells were infected with M7 baboon type C virus. The progeny of this infection included viral pseudotypes that contained M7 helper virus and endogenous 30S retrovirus-associated sequences derived from SC-1 cells (RAS). The RAS sequences are unrelated by nucleic acid hybridization criteria to previously described types of murine retroviruses and do not code for known murine viral structural proteins. The RAS genome is present in multiple copies in the DNA of laboratory (M. musculus) and Asian (M. caroli and M. cervicolor) mice, is expressed in the RNA of uninfected mouse cells, and can be efficiently rescued by type C, but not type B, viruses. RAS is closely related to 30S virus-associated RNA in NIH/3T3 and BALB/c JLSV-9 cells and may be analogous to the defective 30S RNA sequences found in rats."}
{"id": "PMID:207888", "title": "Rescue of infectious virus from permissive monkey cells containing simian virus 40 DNA fragments.", "content": "Permissive TC7 cells were separately transfected with simian virus 40 (SV40) EcoRI/Hap II A (74% genome) DNA fragments and EcoRI/Hap II B (26% genome) DNA fragments in the presence of DEAE-dextran. Fusion of the progeny of recipient cells receiving the A fragment, TC7 (SV40/74) cells, with TC7 (SV40/26) cells, which had received the B fragment, resulted in SV40 rescue. TC7 (SV40/74 + 26) cells, which had simultaneously received both complementary subgenomes, either spontaneously produced SV40 upon subculture or yielded virus upon treatment with iododeoxyuridine. In addition, fusion of rat cells containing the EcoRI/Hap II A fragment with TC7 (SV40/26) cells resulted in SV40 rescue. Cytopathology, V-antigen production, neutralization, and electron microscopy were parameters used to verify that the rescued virus was SV40. No infectious virus was produced when the combinations of cells fused did not total a complete SV40 genome equivalent.", "contents": "Rescue of infectious virus from permissive monkey cells containing simian virus 40 DNA fragments. Permissive TC7 cells were separately transfected with simian virus 40 (SV40) EcoRI/Hap II A (74% genome) DNA fragments and EcoRI/Hap II B (26% genome) DNA fragments in the presence of DEAE-dextran. Fusion of the progeny of recipient cells receiving the A fragment, TC7 (SV40/74) cells, with TC7 (SV40/26) cells, which had received the B fragment, resulted in SV40 rescue. TC7 (SV40/74 + 26) cells, which had simultaneously received both complementary subgenomes, either spontaneously produced SV40 upon subculture or yielded virus upon treatment with iododeoxyuridine. In addition, fusion of rat cells containing the EcoRI/Hap II A fragment with TC7 (SV40/26) cells resulted in SV40 rescue. Cytopathology, V-antigen production, neutralization, and electron microscopy were parameters used to verify that the rescued virus was SV40. No infectious virus was produced when the combinations of cells fused did not total a complete SV40 genome equivalent."}
{"id": "PMID:207889", "title": "Synthesis of viral and host DNA in isolated chromatin from herpes simplex virus-infected HeLa cells.", "content": "DNA synthesis in chromatin isolated from herpes simplex virus type 1-infected HeLa cells (HSV chromatin) was examined in vitro. The HSV chromatin was found to carry out an initial limited synthesis of DNA in vitro, 50 to 64 pmol of dTMP incorporated in 10(6) nuclei per 10 min, which is comparable to that found in nuclei isolated from HSV-infected cells. DNA synthesis in vitro proceeded for only 30 min, and both HSV DNA and host DNA were synthesized in significant amounts. The HSV and host DNA synthesis in isolated chromatin were inhibited to the same extent by anti-HSV antiserum or by phosphonoacetic acid. The results indicate that the HSV-induced DNA polymerase is most likely involved in the synthesis of host and HSV DNA in isolated chromatin, even though this chromatin contains small amounts of the host gamma-polymerase in addition to the HSV-induced DNA polymerase. The HSV chromatin contains no detectable levels of DNA polymerases alpha and beta, even though infected cells have normal, or increased, levels of these enzymes.", "contents": "Synthesis of viral and host DNA in isolated chromatin from herpes simplex virus-infected HeLa cells. DNA synthesis in chromatin isolated from herpes simplex virus type 1-infected HeLa cells (HSV chromatin) was examined in vitro. The HSV chromatin was found to carry out an initial limited synthesis of DNA in vitro, 50 to 64 pmol of dTMP incorporated in 10(6) nuclei per 10 min, which is comparable to that found in nuclei isolated from HSV-infected cells. DNA synthesis in vitro proceeded for only 30 min, and both HSV DNA and host DNA were synthesized in significant amounts. The HSV and host DNA synthesis in isolated chromatin were inhibited to the same extent by anti-HSV antiserum or by phosphonoacetic acid. The results indicate that the HSV-induced DNA polymerase is most likely involved in the synthesis of host and HSV DNA in isolated chromatin, even though this chromatin contains small amounts of the host gamma-polymerase in addition to the HSV-induced DNA polymerase. The HSV chromatin contains no detectable levels of DNA polymerases alpha and beta, even though infected cells have normal, or increased, levels of these enzymes."}
{"id": "PMID:207890", "title": "Mechanism of poliovirus inactivation by ammonia.", "content": "Poliovirus inactivation by ammonia causes a slight reduction in the sedimentation coefficients of viral particles, but has no detectable effect on either the electrophoretic pattern of viral capsid proteins or the isoelectric points of inactivated particles. These virions still attach to cells, but are unable to repress host translation or stimulate the synthesis of detectable amounts of viral RNA. Although ammonia has no detectable effect on naked poliovirus RNA, it causes cleavage of this RNA when still within viral particles. Therefore, the RNA genome appears to be the only component of poliovirus significantly affected by ammonia.", "contents": "Mechanism of poliovirus inactivation by ammonia. Poliovirus inactivation by ammonia causes a slight reduction in the sedimentation coefficients of viral particles, but has no detectable effect on either the electrophoretic pattern of viral capsid proteins or the isoelectric points of inactivated particles. These virions still attach to cells, but are unable to repress host translation or stimulate the synthesis of detectable amounts of viral RNA. Although ammonia has no detectable effect on naked poliovirus RNA, it causes cleavage of this RNA when still within viral particles. Therefore, the RNA genome appears to be the only component of poliovirus significantly affected by ammonia."}
{"id": "PMID:207891", "title": "Recently replicated simian virus 40 DNA is a preferential template for transcription and replication.", "content": "The template activities for the processes of replication and transcription were compared for recently replicated (\"new\") and uniformly labeled (\"old\") simian virus 40 (SV40) DNA in infected monkey cells (line TC7). New SV40 DNA (pulse-labeled for 1 h) served as a template for a second round of replication with a relatively high probability (8% of the DNA replicated per h) for a period of 5 h, after which time its template activity rapidly decreased by severalfold. Old SV40 DNA (labeled for 24 h) functioned as a template for replication with a constant probability (1.8% of the DNA replicated per h) for at least 12 h. The proportion of RNA polymerase with nonreplicated and with recently replicated (bromodeoxyuridine-substituted) viral DNA was determined by an assay that used the Triton-soluble SV40 transcription complex. The proportion of RNA polymerase associated with nonreplicated SV40 DNA decreased very slowly (to 50% in 6 h), strongly suggesting that replicating viral genomes are not required as templates for the initiation of late transcription. This hypothesis was supported by the finding that the RNA synthesized in vitro was associated with covalently closed circular SV40 DNA. Furthermore, after 9 h in bromodeoxyuridine, the recently replicated viral DNA had nearly three times more RNA polymerase per unit of DNA than did the nonreplicated DNA. We thus conclude that recently replicated SV40 DNA is utilized preferentially as a template for transcription and for replication.", "contents": "Recently replicated simian virus 40 DNA is a preferential template for transcription and replication. The template activities for the processes of replication and transcription were compared for recently replicated (\"new\") and uniformly labeled (\"old\") simian virus 40 (SV40) DNA in infected monkey cells (line TC7). New SV40 DNA (pulse-labeled for 1 h) served as a template for a second round of replication with a relatively high probability (8% of the DNA replicated per h) for a period of 5 h, after which time its template activity rapidly decreased by severalfold. Old SV40 DNA (labeled for 24 h) functioned as a template for replication with a constant probability (1.8% of the DNA replicated per h) for at least 12 h. The proportion of RNA polymerase with nonreplicated and with recently replicated (bromodeoxyuridine-substituted) viral DNA was determined by an assay that used the Triton-soluble SV40 transcription complex. The proportion of RNA polymerase associated with nonreplicated SV40 DNA decreased very slowly (to 50% in 6 h), strongly suggesting that replicating viral genomes are not required as templates for the initiation of late transcription. This hypothesis was supported by the finding that the RNA synthesized in vitro was associated with covalently closed circular SV40 DNA. Furthermore, after 9 h in bromodeoxyuridine, the recently replicated viral DNA had nearly three times more RNA polymerase per unit of DNA than did the nonreplicated DNA. We thus conclude that recently replicated SV40 DNA is utilized preferentially as a template for transcription and for replication."}
{"id": "PMID:207892", "title": "More precise location of the polycytidylic acid tract in foot and mouth disease virus RNA.", "content": "The polycytidylic acid [poly(C)] tract in foot and mouth disease virus RNA has been located about 400 nucleotides from the 5' end of the RNA by analysis of the products from the digestion of the RNA with RNase H in the presence of oligodeoxyguanylic acid [oligo(dG)]. This treatment produces a small fragment (S) containing the small protein covalently linked to the RNA and a large fragment (L) that migrates faster than untreated RNA on low-percentage polyacrylamide gels, lacks the poly(C) tract as shown by RNase T1 digestion and oligo(dG)-cellulose binding, and is no longer infective. Polyacrylamide gel electrophoresis of fragment S suggests that it is about 400 nucleotides long, in agreement with the size estimated from the proportion of radioactivity in the fragment. Analysis of the RNase T1 digestion products of S shows that it contains only those oligonucleotides mapping close to the poly(C) tract that is situated near the 5' end of the virus RNA.", "contents": "More precise location of the polycytidylic acid tract in foot and mouth disease virus RNA. The polycytidylic acid [poly(C)] tract in foot and mouth disease virus RNA has been located about 400 nucleotides from the 5' end of the RNA by analysis of the products from the digestion of the RNA with RNase H in the presence of oligodeoxyguanylic acid [oligo(dG)]. This treatment produces a small fragment (S) containing the small protein covalently linked to the RNA and a large fragment (L) that migrates faster than untreated RNA on low-percentage polyacrylamide gels, lacks the poly(C) tract as shown by RNase T1 digestion and oligo(dG)-cellulose binding, and is no longer infective. Polyacrylamide gel electrophoresis of fragment S suggests that it is about 400 nucleotides long, in agreement with the size estimated from the proportion of radioactivity in the fragment. Analysis of the RNase T1 digestion products of S shows that it contains only those oligonucleotides mapping close to the poly(C) tract that is situated near the 5' end of the virus RNA."}
{"id": "PMID:207893", "title": "Structural analysis of viral replicative intermediates isolated from adenovirus type 2-infected HeLa cell nuclei.", "content": "Deoxyribonucleoprotein complexes released 17 h postinfection from adenovirus type 1 (Ad2)-infected HeLa cell nuclei were shown by electron microscopy to contain filaments much thicker (about 200 A [20 nm]) than double-stranded DNA (about 20 A [2 nm]). The complexes were partially purified through a linear sucrose gradient, concentrated, and further purified in a metrizamide gradient. The major protein present in the complexes was identified as the 72,000-dalton (72K), adenovirus-coded single-stranded DNA-binding protein (72K DBP). Three types of complexes have been visualized by electron microscopy. Some linear complexes were uniformly thick, and their length corresponded roughly to that of the adenovirus genome. Other linear genome-length complexes appeared to consist of a thick filament connected to a thinner filament with the diameter of double-stranded DNA. Forked complexes consisting of one thick filament connected to a genome-length, thinner double-stranded DNA filament were also visualized. Both thick and thin filaments were sensitive to DNase and not to RNase, but only the thick filaments were digested by the single-strand-specific Neurospora crassa nuclease, indicating that they correspond to a complex of 72K DBP and Ad2 single-stranded DNA. Experiments with anti-72K DBP immunoglobulins indicated that these nucleoprotein complexes, containing the 72K DBP, correspond to replicative intermediates. Both strands of the Ad2 genome were found associated to the 72K DBP. Altogether, our results establish the in vivo association of the 72K DBP with adenovirus single-stranded DNA, as previously suggested from in vitro studies, and support a strand displacement mechanism for Ad2 DNA replication, in which both strands can be displaced. In addition, our results indicate that, late in infection, histones are not bound to adenovirus DNA in the form of a nucleosomal chromatine-like structure.", "contents": "Structural analysis of viral replicative intermediates isolated from adenovirus type 2-infected HeLa cell nuclei. Deoxyribonucleoprotein complexes released 17 h postinfection from adenovirus type 1 (Ad2)-infected HeLa cell nuclei were shown by electron microscopy to contain filaments much thicker (about 200 A [20 nm]) than double-stranded DNA (about 20 A [2 nm]). The complexes were partially purified through a linear sucrose gradient, concentrated, and further purified in a metrizamide gradient. The major protein present in the complexes was identified as the 72,000-dalton (72K), adenovirus-coded single-stranded DNA-binding protein (72K DBP). Three types of complexes have been visualized by electron microscopy. Some linear complexes were uniformly thick, and their length corresponded roughly to that of the adenovirus genome. Other linear genome-length complexes appeared to consist of a thick filament connected to a thinner filament with the diameter of double-stranded DNA. Forked complexes consisting of one thick filament connected to a genome-length, thinner double-stranded DNA filament were also visualized. Both thick and thin filaments were sensitive to DNase and not to RNase, but only the thick filaments were digested by the single-strand-specific Neurospora crassa nuclease, indicating that they correspond to a complex of 72K DBP and Ad2 single-stranded DNA. Experiments with anti-72K DBP immunoglobulins indicated that these nucleoprotein complexes, containing the 72K DBP, correspond to replicative intermediates. Both strands of the Ad2 genome were found associated to the 72K DBP. Altogether, our results establish the in vivo association of the 72K DBP with adenovirus single-stranded DNA, as previously suggested from in vitro studies, and support a strand displacement mechanism for Ad2 DNA replication, in which both strands can be displaced. In addition, our results indicate that, late in infection, histones are not bound to adenovirus DNA in the form of a nucleosomal chromatine-like structure."}
{"id": "PMID:207894", "title": "Anatomy of herpes simplex virus (HSV) DNA. X. Mapping of viral genes by analysis of polypeptides and functions specified by HSV-1 X HSV-2 recombinants.", "content": "In an earlier paper (Morse et al., J. Virol 24:231--248, 1977) we reported on the provenance of the DNA sequences in 26 herpes simplex virus type 1 (HSV-1) X HSV-2 recombinants as determined from analyses of their DNAs with at least five restriction endonucleases. This report deals with the polypeptides specified by the recombinants and by their HSV-1 and HSV-2 parents. We have identified (i) the corresponding HSV-1 and HSV-2 polypeptides with molecular weights ranging from 20,000 to more than 200,000, (ii) the polypeptides that undergo rapid post-translational processing, and (iii) polypeptides that vary intratypically in apparent molecular weight. By comparing the segregation patterns of the polypeptides with those of the DNA sequence of the recombinants, we have mapped the templates specifying 26 polypeptides and several viral functions on the physical map of HSV DNA. The data show the following: (i) alpha polypeptides map at the termini of the L and S components of the 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. (ii) Templates specifying beta and gamma polypeptides map in the L component and appear to be randomly distributed. (iii) Thymidine kinase and resistance to phosphonoacetic acid mapped in the L component. In addition, we have taken advantage of the rapid inhibition of host protein synthesis characteristic of HSV-2 infections and syncytial plaque morphology to also map the template(s) responsible for these functions in the L component. The implications of the template arrangement in HSV DNA are discussed.", "contents": "Anatomy of herpes simplex virus (HSV) DNA. X. Mapping of viral genes by analysis of polypeptides and functions specified by HSV-1 X HSV-2 recombinants. In an earlier paper (Morse et al., J. Virol 24:231--248, 1977) we reported on the provenance of the DNA sequences in 26 herpes simplex virus type 1 (HSV-1) X HSV-2 recombinants as determined from analyses of their DNAs with at least five restriction endonucleases. This report deals with the polypeptides specified by the recombinants and by their HSV-1 and HSV-2 parents. We have identified (i) the corresponding HSV-1 and HSV-2 polypeptides with molecular weights ranging from 20,000 to more than 200,000, (ii) the polypeptides that undergo rapid post-translational processing, and (iii) polypeptides that vary intratypically in apparent molecular weight. By comparing the segregation patterns of the polypeptides with those of the DNA sequence of the recombinants, we have mapped the templates specifying 26 polypeptides and several viral functions on the physical map of HSV DNA. The data show the following: (i) alpha polypeptides map at the termini of the L and S components of the 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. (ii) Templates specifying beta and gamma polypeptides map in the L component and appear to be randomly distributed. (iii) Thymidine kinase and resistance to phosphonoacetic acid mapped in the L component. In addition, we have taken advantage of the rapid inhibition of host protein synthesis characteristic of HSV-2 infections and syncytial plaque morphology to also map the template(s) responsible for these functions in the L component. The implications of the template arrangement in HSV DNA are discussed."}
{"id": "PMID:207895", "title": "Biosynthesis, immunological specificity, and intracellular distribution of the simian virus 40-specific protein induced by the nondefective hybrid Ad2+ND1.", "content": "Ad2(+)ND(1), a nondefective hybrid virus containing a segment of the early region of simian virus 40 (SV40) DNA covalently inserted into the human adenovirus 2 genome, enhances the growth of human adenoviruses in simian cells and induces the SV40 U antigen. This hybrid previously has been shown to code for a 28,000 (28K) molecular weight protein not present in wild-type adenovirus 2-infected cells. By radioimmunoprecipitation using sera from hamsters bearing SV40-specific tumors, we have established that the Ad2(+)ND(1)-induced 28K protein is SV40-specific. This Ad2(+)ND(1)-induced protein is synthesized as a 30K molecular weight precursor, which is detectable only when infected cells are pulse-labeled in the presence of the protease inhibitor tosylamino phenylethyl chloromethyl ketone. Upon fractionation of labeled cell extracts, about 80% of the 28K protein is found in the plasma membrane fraction, whereas the remaining 20% is associated with the outer nuclear membrane. This protein is not detectable either in the nucleus or in the cytoplasm. Blockage of proteolytic cleavage by tosylamino phenylethyl chloromethyl ketone did not alter the topographic distribution of this SV40-specific protein, although the amount of the precursor protein in the outer nuclear membrane increased fourfold while that in the plasma membrane was proportionately decreased. This result suggests that the 28K protein is transferred from the outer nuclear membrane to the plasma membrane after posttranslational cleavage of the 30K precursor polypeptide. These data offer further support to the proposal that the 28K protein contains the determinants for SV40 U antigen and is responsible for SV40 enhancement of adenovirus growth in simian cells.", "contents": "Biosynthesis, immunological specificity, and intracellular distribution of the simian virus 40-specific protein induced by the nondefective hybrid Ad2+ND1. Ad2(+)ND(1), a nondefective hybrid virus containing a segment of the early region of simian virus 40 (SV40) DNA covalently inserted into the human adenovirus 2 genome, enhances the growth of human adenoviruses in simian cells and induces the SV40 U antigen. This hybrid previously has been shown to code for a 28,000 (28K) molecular weight protein not present in wild-type adenovirus 2-infected cells. By radioimmunoprecipitation using sera from hamsters bearing SV40-specific tumors, we have established that the Ad2(+)ND(1)-induced 28K protein is SV40-specific. This Ad2(+)ND(1)-induced protein is synthesized as a 30K molecular weight precursor, which is detectable only when infected cells are pulse-labeled in the presence of the protease inhibitor tosylamino phenylethyl chloromethyl ketone. Upon fractionation of labeled cell extracts, about 80% of the 28K protein is found in the plasma membrane fraction, whereas the remaining 20% is associated with the outer nuclear membrane. This protein is not detectable either in the nucleus or in the cytoplasm. Blockage of proteolytic cleavage by tosylamino phenylethyl chloromethyl ketone did not alter the topographic distribution of this SV40-specific protein, although the amount of the precursor protein in the outer nuclear membrane increased fourfold while that in the plasma membrane was proportionately decreased. This result suggests that the 28K protein is transferred from the outer nuclear membrane to the plasma membrane after posttranslational cleavage of the 30K precursor polypeptide. These data offer further support to the proposal that the 28K protein contains the determinants for SV40 U antigen and is responsible for SV40 enhancement of adenovirus growth in simian cells."}
{"id": "PMID:207896", "title": "Intramembrane changes occurring during maturation of herpes simplex virus type 1: freeze-fracture study.", "content": "During the maturation of two strains of herpes simplex virus type 1 (VR3 and Patton), intramembrane changes were detected with the freeze-fracture technique in the viral envelope and the infected cell plasma membrane, and these changes were compared with data obtained from thin sections. Regardless of the strain, the inner leaflet of the viral envelope of extracellular virions was characterized by a density of intramembrane particles (IMP) three times larger than the host nuclear and plasma membrane. Addition of IMP, which probably represent virus-coded proteins, was detected in the viral envelope only after budding from the nuclear membrane, whereas it occurred during envelopment of capsids at cytoplasmic vacuoles. Fused membranes also showed one of their fracture faces covered with a high density of IMP similar to that of the mature virion envelope. The internal side of the membrane leaflet bearing these numerous particles was always characterized by the presence of an electron-dense material in thin sections. In addition, the plasma membrane of fibroblasts and Vero cells showed strain-specific changes: patches of closely packed IMP were observed with the VR3 strain, whereas ridges almost devoid of IMP characterized the plasmalemma of cells infected with the Patton strain. These intramembrane changes, however, were not observed as early as herpes membrane antigens. Thus, application of the freeze-fracture technique to herpes simplex virus type 1-infected cells revealed striking structural differences between viral and uninfected cell membranes. These differences are probably related to insertion and clustering of virus-coded proteins in the hydrophobic part of the membrane bilayer.", "contents": "Intramembrane changes occurring during maturation of herpes simplex virus type 1: freeze-fracture study. During the maturation of two strains of herpes simplex virus type 1 (VR3 and Patton), intramembrane changes were detected with the freeze-fracture technique in the viral envelope and the infected cell plasma membrane, and these changes were compared with data obtained from thin sections. Regardless of the strain, the inner leaflet of the viral envelope of extracellular virions was characterized by a density of intramembrane particles (IMP) three times larger than the host nuclear and plasma membrane. Addition of IMP, which probably represent virus-coded proteins, was detected in the viral envelope only after budding from the nuclear membrane, whereas it occurred during envelopment of capsids at cytoplasmic vacuoles. Fused membranes also showed one of their fracture faces covered with a high density of IMP similar to that of the mature virion envelope. The internal side of the membrane leaflet bearing these numerous particles was always characterized by the presence of an electron-dense material in thin sections. In addition, the plasma membrane of fibroblasts and Vero cells showed strain-specific changes: patches of closely packed IMP were observed with the VR3 strain, whereas ridges almost devoid of IMP characterized the plasmalemma of cells infected with the Patton strain. These intramembrane changes, however, were not observed as early as herpes membrane antigens. Thus, application of the freeze-fracture technique to herpes simplex virus type 1-infected cells revealed striking structural differences between viral and uninfected cell membranes. These differences are probably related to insertion and clustering of virus-coded proteins in the hydrophobic part of the membrane bilayer."}
{"id": "PMID:207897", "title": "Structural components of mouse mammary tumor virus. II. Isolation and purification of virion polypeptides.", "content": "Mouse mammary tumor virus (MMTV) glycoproteins and nonglycosylated polypeptides were purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Primary amino groups were labeled with fluorescamine to enable visualization of MMTV polypeptides in the gels. Protein bands were sliced from the gels and eluted with 90 to 95% recovery. Eight MMTV polypeptides, including three of the major viral components as well as five minor proteins, were routinely obtained. Double diffusion assays and immunoelectrophoresis confirmed the retention of antigenicity identical to that of untreated MMTV virions. Antisera obtained from MMTV-free BALB/c mice immunized with these purified proteins reacted with the polypeptide immunogen as well as with detergent-disrupted MMTV virions from mouse milk or cell culture. Double diffusion assays using the specific mouse antisera failed to detect any cross-reactivity among the isolated polypeptides. A hemagglutination-inhibition assay demonstrated that the ability of MMTV virions to inhibit the hemagglutinating properties of influenza virus resides in the glycosylated polypeptides gp52, gp37.7, and gp33.", "contents": "Structural components of mouse mammary tumor virus. II. Isolation and purification of virion polypeptides. Mouse mammary tumor virus (MMTV) glycoproteins and nonglycosylated polypeptides were purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Primary amino groups were labeled with fluorescamine to enable visualization of MMTV polypeptides in the gels. Protein bands were sliced from the gels and eluted with 90 to 95% recovery. Eight MMTV polypeptides, including three of the major viral components as well as five minor proteins, were routinely obtained. Double diffusion assays and immunoelectrophoresis confirmed the retention of antigenicity identical to that of untreated MMTV virions. Antisera obtained from MMTV-free BALB/c mice immunized with these purified proteins reacted with the polypeptide immunogen as well as with detergent-disrupted MMTV virions from mouse milk or cell culture. Double diffusion assays using the specific mouse antisera failed to detect any cross-reactivity among the isolated polypeptides. A hemagglutination-inhibition assay demonstrated that the ability of MMTV virions to inhibit the hemagglutinating properties of influenza virus resides in the glycosylated polypeptides gp52, gp37.7, and gp33."}
{"id": "PMID:207898", "title": "Restriction enzyme sites on the avian RNA tumor virus genome.", "content": "Full-size single-stranded DNA transcripts of the avian RNA tumor virus genome were isolated from the products of the endogenous reaction of detergent-disrupted avian sarcoma virus particles. These transcripts were converted with Escherichia coli DNA polymerase I and 32P-labeled nucleoside triphosphates into labeled double-stranded DNA. The latter DNA was used to map the sites of action of seven restriction enzymes (Pvu I, Hpa I, Kpn I, Xba I, EcoRI, HindIII, and Xho I) on the genome of three strains of avian sarcoma virus (Prague B, Prague C, and Bratislava 77).", "contents": "Restriction enzyme sites on the avian RNA tumor virus genome. Full-size single-stranded DNA transcripts of the avian RNA tumor virus genome were isolated from the products of the endogenous reaction of detergent-disrupted avian sarcoma virus particles. These transcripts were converted with Escherichia coli DNA polymerase I and 32P-labeled nucleoside triphosphates into labeled double-stranded DNA. The latter DNA was used to map the sites of action of seven restriction enzymes (Pvu I, Hpa I, Kpn I, Xba I, EcoRI, HindIII, and Xho I) on the genome of three strains of avian sarcoma virus (Prague B, Prague C, and Bratislava 77)."}
{"id": "PMID:207899", "title": "Control of protein synthesis in extracts from poliovirus-infected cells. I. mRNA discrimination by crude initiation factors.", "content": "By using cell-free systems prepared from uninfected and poliovirus-infected cells, we have been able to demonstrate that crude preparations of initiation factors from infected cells do not stimulate the initiation of translation by polyribosomes containing endogenous host cell mRNA. When tested with polysomes containing endogenous viral mRNA, however, they were able to stimulate initiation of translation nearly as well as uninfected cell initiation factors. The uninfected cell initiation factor preparations were able to stimulate initiation of translation of both cell and viral mRNA. The results indicate an mRNA-specific activity present in crude initiation factor preparations from infected cells. Furthermore, the ability of eIF2 from infected cells to form a ternary complex with GTP and formyl [35S]methionine-tRNAfmet, an mRNA-independent step in initiation, was found not to be deficient. Implications of these data for proposed mechanisms of poliovirus-induced host cell shutoff are discussed.", "contents": "Control of protein synthesis in extracts from poliovirus-infected cells. I. mRNA discrimination by crude initiation factors. By using cell-free systems prepared from uninfected and poliovirus-infected cells, we have been able to demonstrate that crude preparations of initiation factors from infected cells do not stimulate the initiation of translation by polyribosomes containing endogenous host cell mRNA. When tested with polysomes containing endogenous viral mRNA, however, they were able to stimulate initiation of translation nearly as well as uninfected cell initiation factors. The uninfected cell initiation factor preparations were able to stimulate initiation of translation of both cell and viral mRNA. The results indicate an mRNA-specific activity present in crude initiation factor preparations from infected cells. Furthermore, the ability of eIF2 from infected cells to form a ternary complex with GTP and formyl [35S]methionine-tRNAfmet, an mRNA-independent step in initiation, was found not to be deficient. Implications of these data for proposed mechanisms of poliovirus-induced host cell shutoff are discussed."}
{"id": "PMID:207900", "title": "Identification of virus found in mouse lymphomas induced by HIX murine oncornavirus.", "content": "Lymphomas induced by pure HIX murine leukemia virus in two mouse strains contained large amounts of virus with amphotropic properties. Analysis of tumor derived virus purified by limiting dilution techniques indicated that its interference and neutralization spectra were essentially identical to parental HIX virus and different from eco- and xenotropic viruses. Examination of virus progeny from many individual foci induced by virus derived directly from lymphomas indicated that each infectious unit contained only HIX virus. No evidence of ecotropic virus presence was observed.", "contents": "Identification of virus found in mouse lymphomas induced by HIX murine oncornavirus. Lymphomas induced by pure HIX murine leukemia virus in two mouse strains contained large amounts of virus with amphotropic properties. Analysis of tumor derived virus purified by limiting dilution techniques indicated that its interference and neutralization spectra were essentially identical to parental HIX virus and different from eco- and xenotropic viruses. Examination of virus progeny from many individual foci induced by virus derived directly from lymphomas indicated that each infectious unit contained only HIX virus. No evidence of ecotropic virus presence was observed."}
{"id": "PMID:207901", "title": "Adenovirus-induced inhibition of cellular DNase.", "content": "During the productive infection of KB cells by adenovirus type 5 (Ad5), there is a progressive decrease in the level of cellular DNase activity towards single-stranded DNA, in contrast to DNA polymerase which remains relatively constant throughout the infection. This decrease is prevented by the inhibition of protein synthesis by cycloheximide. The inhibition of DNase activity does not occur after infection by Ad5 ts125, a DNA-negative mutant which fails to induce the adenovirus-specific DNA binding protein. In contrast, infection by Ad5 ts36, a DNA-negative mutant which complements ts125, does result in decreased levels of DNase. A mechanism is discussed in which the DNA binding protein protects viral replicative intermediates from degradation by cellular DNase.", "contents": "Adenovirus-induced inhibition of cellular DNase. During the productive infection of KB cells by adenovirus type 5 (Ad5), there is a progressive decrease in the level of cellular DNase activity towards single-stranded DNA, in contrast to DNA polymerase which remains relatively constant throughout the infection. This decrease is prevented by the inhibition of protein synthesis by cycloheximide. The inhibition of DNase activity does not occur after infection by Ad5 ts125, a DNA-negative mutant which fails to induce the adenovirus-specific DNA binding protein. In contrast, infection by Ad5 ts36, a DNA-negative mutant which complements ts125, does result in decreased levels of DNase. A mechanism is discussed in which the DNA binding protein protects viral replicative intermediates from degradation by cellular DNase."}
{"id": "PMID:207902", "title": "RNA polymerase associated with human rotaviruses in diarrhea stools.", "content": "RNA polymerase activity was detected in six stools which were partially purified by high-speed centrifugation from infants with rotavirus gastroenteritis, but was not detected in five stools which were negative for rotavirus by counterimmunoelectrophoresis and radioimmunoassay. The polymerase activity was associated with the 1.38-g/ml rotavirus band after purification in a CsCl gradient.", "contents": "RNA polymerase associated with human rotaviruses in diarrhea stools. RNA polymerase activity was detected in six stools which were partially purified by high-speed centrifugation from infants with rotavirus gastroenteritis, but was not detected in five stools which were negative for rotavirus by counterimmunoelectrophoresis and radioimmunoassay. The polymerase activity was associated with the 1.38-g/ml rotavirus band after purification in a CsCl gradient."}
{"id": "PMID:207906", "title": "Simultaneous serum and CSF antibodies in herpes simplex virus encephalitis.", "content": "Serial concomitant paired sera (S) and CSF were taken from eight patients with biopsy-proved herpes simplex virus encephalitis (HSVE). These specimen pairs were compared with 28 others from patients with various neurologic conditions. Before and after reduction with 2-mercaptoethanol, a ratio of S/CSF antibody titers of less than or equal to 20 with either the passive hemagglutinating (PHA) or immune adherence hemagglutinating (IAHA) antibody tests occurred in every patient with HSVE. Diagnostic S/CSF ratios were noted in three patients before biopsy of the brain and in four patients by the tenth day of neurologic disease. Among control subjects, a ratio of S/CSF titers greater than 20 was observed in all but four patients. Each of the latter patients had neurologic diagnoses easily distinguishable from HSVE. The PHA or IAHA S/CSF ratio offers a rapid, reliable method for the diagnosis of HSVE (P less than .001).", "contents": "Simultaneous serum and CSF antibodies in herpes simplex virus encephalitis. Serial concomitant paired sera (S) and CSF were taken from eight patients with biopsy-proved herpes simplex virus encephalitis (HSVE). These specimen pairs were compared with 28 others from patients with various neurologic conditions. Before and after reduction with 2-mercaptoethanol, a ratio of S/CSF antibody titers of less than or equal to 20 with either the passive hemagglutinating (PHA) or immune adherence hemagglutinating (IAHA) antibody tests occurred in every patient with HSVE. Diagnostic S/CSF ratios were noted in three patients before biopsy of the brain and in four patients by the tenth day of neurologic disease. Among control subjects, a ratio of S/CSF titers greater than 20 was observed in all but four patients. Each of the latter patients had neurologic diagnoses easily distinguishable from HSVE. The PHA or IAHA S/CSF ratio offers a rapid, reliable method for the diagnosis of HSVE (P less than .001)."}
{"id": "PMID:207913", "title": "Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. I. Evidence for decrease of vector mosquitoes.", "content": "Mosquito collections by using light traps have been carried out at 10 to 11 stations in Kyoto City area at intervals of about 10 days every year. Mean percent indexes (MPI), being calculated from the data of mosquito collections, were used for comparison of the annual abundance of mosquitoes. It is no doubt that Culex tritaeniorhynchus summorosus has decreased recently and this decrease is correlated with the reduction of human patients of Japanese encephalitis. Wide use of two herbicides, CNP and nitrofen, for rice plant cultivation, may probably be one of the reasons for the decrease of the mosquitoes.", "contents": "Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. I. Evidence for decrease of vector mosquitoes. Mosquito collections by using light traps have been carried out at 10 to 11 stations in Kyoto City area at intervals of about 10 days every year. Mean percent indexes (MPI), being calculated from the data of mosquito collections, were used for comparison of the annual abundance of mosquitoes. It is no doubt that Culex tritaeniorhynchus summorosus has decreased recently and this decrease is correlated with the reduction of human patients of Japanese encephalitis. Wide use of two herbicides, CNP and nitrofen, for rice plant cultivation, may probably be one of the reasons for the decrease of the mosquitoes."}
{"id": "PMID:207914", "title": "Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. II. Annual patterns of virus dissemination on virus recoveries from unfed Culex tritaeniorhynchus summorosus.", "content": "Annual patterns of dissemination of Japanese encephalitis virus in vector mosquitoes have been investigated at the main collection station from 1965 through 1973 at some other stations from 1969 through 1971. The virus was recovered usually from Culex tritaeniorhynchus summorosus during a period of about a month from July to August every year till 1969, and from August to September after 1970, although at some of the stations the virus was recovered intermittently for longer or shorter terms. Higher infection rates were recorded with the mosquitoes caught at the stations near to pig sheds than at the stations far from pig sheds. The infection rates at the peak of virus recovery in high epidemic year (1965 to 1967) were higher, being over 2%, than those in lower or latent epidemic years (1968 to 1973). Human patients of Japanese encephalitis were found in 17 to 20 days after the appearance of the highest peak of the infection rate in mosquitoes.", "contents": "Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. II. Annual patterns of virus dissemination on virus recoveries from unfed Culex tritaeniorhynchus summorosus. Annual patterns of dissemination of Japanese encephalitis virus in vector mosquitoes have been investigated at the main collection station from 1965 through 1973 at some other stations from 1969 through 1971. The virus was recovered usually from Culex tritaeniorhynchus summorosus during a period of about a month from July to August every year till 1969, and from August to September after 1970, although at some of the stations the virus was recovered intermittently for longer or shorter terms. Higher infection rates were recorded with the mosquitoes caught at the stations near to pig sheds than at the stations far from pig sheds. The infection rates at the peak of virus recovery in high epidemic year (1965 to 1967) were higher, being over 2%, than those in lower or latent epidemic years (1968 to 1973). Human patients of Japanese encephalitis were found in 17 to 20 days after the appearance of the highest peak of the infection rate in mosquitoes."}
{"id": "PMID:207916", "title": "Nature of catecholamine-like actions of ATP and other energy rich nucleotides on the bullfrog atrial muscle.", "content": "The nature of the inotropic actions of exogeneously applied ATP and related compounds (AMP-PNP, GTP, GMP and guanosine) was studied in comparison with that of adrenaline on the bullfrog atrial muscle under voltage clamped and unclamped conditions with the double-gap method. ATP and GTP (10(-6-) - 10(-3) M) produced an immediate positive inotropic effect similar to that achieved with adrenaline. Dose-response curves of these drugs fitted the theoretical dose-response relations, but the curves of ATP and GTP were not significantly altered by propranolol. Under voltage clamped conditions, ATP, AMP-PNP (non-hydrolyzable analogue of ATP) and GTP augmentated the calcium inward current (ICa), ICa-dependent tension and the delayed outward current (Ix) as adrenaline. On the other hand, GMP and guanosine, which have a purine-ribose base but not a high energy phosphate bond, produced a negative inotropic effect, and depressed the Ix as adenosine. All these nucleotides and nucleosides inhibited the ICa-independent tonic tension. The facts that GTP and AMP-PNP showed the same effect as ATP indicated that neither the energy liberation from the phosphate bond nor the substrate for cyclic AMP formation is involved in their positive inotropic effects. It is proposed that the energy rich nucleotides modulate the adenylate cyclase activity, being mediated by some receptor located at the outer surface of the membrane other than beta-adrenergic receptor.", "contents": "Nature of catecholamine-like actions of ATP and other energy rich nucleotides on the bullfrog atrial muscle. The nature of the inotropic actions of exogeneously applied ATP and related compounds (AMP-PNP, GTP, GMP and guanosine) was studied in comparison with that of adrenaline on the bullfrog atrial muscle under voltage clamped and unclamped conditions with the double-gap method. ATP and GTP (10(-6-) - 10(-3) M) produced an immediate positive inotropic effect similar to that achieved with adrenaline. Dose-response curves of these drugs fitted the theoretical dose-response relations, but the curves of ATP and GTP were not significantly altered by propranolol. Under voltage clamped conditions, ATP, AMP-PNP (non-hydrolyzable analogue of ATP) and GTP augmentated the calcium inward current (ICa), ICa-dependent tension and the delayed outward current (Ix) as adrenaline. On the other hand, GMP and guanosine, which have a purine-ribose base but not a high energy phosphate bond, produced a negative inotropic effect, and depressed the Ix as adenosine. All these nucleotides and nucleosides inhibited the ICa-independent tonic tension. The facts that GTP and AMP-PNP showed the same effect as ATP indicated that neither the energy liberation from the phosphate bond nor the substrate for cyclic AMP formation is involved in their positive inotropic effects. It is proposed that the energy rich nucleotides modulate the adenylate cyclase activity, being mediated by some receptor located at the outer surface of the membrane other than beta-adrenergic receptor."}
{"id": "PMID:207923", "title": "[Virilizing adrenal cortical tumors in childhood (author's transl)].", "content": "We report on four patients, aged seven months to seven years, with virilizing adrenal cortical tumors. Diagnosis was made by clinical and laboratory data. Tumor localisation was achieved preoperatively in three patients. In two patients both androgen and glucocorticoid excretion were elevated. In three patients histological examination showed a carcinoma, in one patient an adenoma was suggested. There were no metastases. In two patients surgical removal was followed by cytostatic therapy, in one of them additional irradiation treatment was carried out. This child died 10 1/2 years later from a metastasizing renal cell carcinoma which originated from the kidney being situated in the irradiated area.", "contents": "[Virilizing adrenal cortical tumors in childhood (author's transl)]. We report on four patients, aged seven months to seven years, with virilizing adrenal cortical tumors. Diagnosis was made by clinical and laboratory data. Tumor localisation was achieved preoperatively in three patients. In two patients both androgen and glucocorticoid excretion were elevated. In three patients histological examination showed a carcinoma, in one patient an adenoma was suggested. There were no metastases. In two patients surgical removal was followed by cytostatic therapy, in one of them additional irradiation treatment was carried out. This child died 10 1/2 years later from a metastasizing renal cell carcinoma which originated from the kidney being situated in the irradiated area."}
{"id": "PMID:207927", "title": "[Decrease in the radiation effect in the lymphoid organs of animals adapting to altitude].", "content": "Adaptation to altitude hypoxia exerts a positive effect on the cell density of lymph organs of gamma-irradiated animals. It also reduces radiation degradation of DNA, its availability to DNase in the nuclear chromatin and disorders in the activity of DNA polymerases. The role of inhibition of radiation-induced degradation of chromatin DNA in the protective effect of altitude adaptation on the cell density of lymph organs is discussed.", "contents": "[Decrease in the radiation effect in the lymphoid organs of animals adapting to altitude]. Adaptation to altitude hypoxia exerts a positive effect on the cell density of lymph organs of gamma-irradiated animals. It also reduces radiation degradation of DNA, its availability to DNase in the nuclear chromatin and disorders in the activity of DNA polymerases. The role of inhibition of radiation-induced degradation of chromatin DNA in the protective effect of altitude adaptation on the cell density of lymph organs is discussed."}
{"id": "PMID:207934", "title": "Surgery of tumors of the subdiaphragmatic inferior vena cava. Report of two cases and review of the literature.", "content": "Two cases of obstruction of the hepatic inferior vena cava (IVC) are presented. In Case 1, the obstruction was due to a calcified thrombus which presumably developed after lower limb trauma 19 months previously. Complete surgical correction was achieved with the aid of deep hypothermia and circulatory arrest. In Case 2, a right atrial tumor was mimicked by a propagating malignant hepatoma. Palliative removal of the tumor cleared the IVC passage. The etiology of tumors of the IVC and their surgical management are discussed.", "contents": "Surgery of tumors of the subdiaphragmatic inferior vena cava. Report of two cases and review of the literature. Two cases of obstruction of the hepatic inferior vena cava (IVC) are presented. In Case 1, the obstruction was due to a calcified thrombus which presumably developed after lower limb trauma 19 months previously. Complete surgical correction was achieved with the aid of deep hypothermia and circulatory arrest. In Case 2, a right atrial tumor was mimicked by a propagating malignant hepatoma. Palliative removal of the tumor cleared the IVC passage. The etiology of tumors of the IVC and their surgical management are discussed."}
{"id": "PMID:207942", "title": "Effect of dietary cyclopropene fatty acids on the octadecenoates of individual lipid classes of rat liver and hepatoma.", "content": "The effect of dietary cyclopropene fatty acids on the concentration of octadecenoate chain positional isomers in individual lipid classes of normal liver, host liver, and hepatoma 7288CTC has been determined. The data revealed the following: (a) Saturated and monoene fatty acid percentages of liver phosphatidylcholines and phosphatidylethanolamines were not affected, but the percentage of saturated fatty acids of the triglycerides and cholesteryl esters was increased while the monoene percentages decreased. (b) Oleate to vaccenate percentage ratios, previously shown to be characteristic of individual lipid classes, were completely disrupted. (c) Oleate concentrations of the two major liver phospholipids were elevated, and vaccenate levels were dramatically reduced. (d) Cyclopropene fatty acids appear to inhibit monoene elongation. (e) The elevated concentrations of oleate indicate that an alternate route of oleate biosynthesis must exist if the delta9 desaturation is inhibited by cyclopropene fatty acids as reported previously. (f) In contrast to liver, oleate and vaccenate concentrations in hepatoma were not affected by the dietary cyclopropene fatty acids.", "contents": "Effect of dietary cyclopropene fatty acids on the octadecenoates of individual lipid classes of rat liver and hepatoma. The effect of dietary cyclopropene fatty acids on the concentration of octadecenoate chain positional isomers in individual lipid classes of normal liver, host liver, and hepatoma 7288CTC has been determined. The data revealed the following: (a) Saturated and monoene fatty acid percentages of liver phosphatidylcholines and phosphatidylethanolamines were not affected, but the percentage of saturated fatty acids of the triglycerides and cholesteryl esters was increased while the monoene percentages decreased. (b) Oleate to vaccenate percentage ratios, previously shown to be characteristic of individual lipid classes, were completely disrupted. (c) Oleate concentrations of the two major liver phospholipids were elevated, and vaccenate levels were dramatically reduced. (d) Cyclopropene fatty acids appear to inhibit monoene elongation. (e) The elevated concentrations of oleate indicate that an alternate route of oleate biosynthesis must exist if the delta9 desaturation is inhibited by cyclopropene fatty acids as reported previously. (f) In contrast to liver, oleate and vaccenate concentrations in hepatoma were not affected by the dietary cyclopropene fatty acids."}
{"id": "PMID:207943", "title": "delta9 Desaturase activity in normal mouse liver and hepatoma SS1K.", "content": "The activity of delta9 desaturase was determined in the microsomal fraction of normal mouse liver and hepatoma SS1K in the presence of the 105,000 x g supernatant. Neither hepatic nor hepatoma soluble fractions were able to modify the low desaturating capacity. Two enzymes from the microsomal electron transport chain associated with delta9 desaturase, namely NADH-cytochrom b5 reductase and NADH-cytochrom C reductase were also measured. The results indicate that the low delta9 desaturase activity in hepatoma SS1K could be related to the reduced amount of desaturase.", "contents": "delta9 Desaturase activity in normal mouse liver and hepatoma SS1K. The activity of delta9 desaturase was determined in the microsomal fraction of normal mouse liver and hepatoma SS1K in the presence of the 105,000 x g supernatant. Neither hepatic nor hepatoma soluble fractions were able to modify the low desaturating capacity. Two enzymes from the microsomal electron transport chain associated with delta9 desaturase, namely NADH-cytochrom b5 reductase and NADH-cytochrom C reductase were also measured. The results indicate that the low delta9 desaturase activity in hepatoma SS1K could be related to the reduced amount of desaturase."}
{"id": "PMID:207946", "title": "Bone infections involving anaerobic bacteria.", "content": "Over 700 cases of anaerobic osteomyelitis have been reported in the literature. Nonetheless, most reviews of osteomyelitis have paid little attention to the potential role of anaerobes in bone infections. There have, as yet, been no prospective studies of osteomyelitis utlizing optimal anaerobic transport and culture techniques. In a retrospective study of osteomyelitis at Wadsworth VA Hospital from 1973--1975, 39 percent of 58 patients with osteomyelitis had an infection involving anaerobes. Anaerobes were isolated from 81 percent of 27 patients whose specimens were cultured anaerobically. Anaerobes were isolated from nine of ten samples of bone. Anaerobic bacteria were part of a mixed flora involving facultative bacteria in all but two cases. All of the patients with anaerobic infection had non-hematogenous osteomyelitis. Non-hematogenous disease comprises 80--90 percent of the osteomyelitis seen in adults. Our experience at Wadsworth VA Hospital and a review of the literature lead us to believe that anaerobes play a much larger role in osteomyelitis than has been appreciated previously. Infections of the calvarium, mastoid, mandible, maxilla and the extremities are most likely to involve anaerobes. Predisposing conditions include paranasal sinusitis, otitis media, periodontal disease, trauma, peripheral vascular disease, peripheral neuropathy and/or chronic osteomyelitis. The presence of a foul odor is a valuable clinical clue to the presence of anaerobes. Bacteroides, fusobacteria and anaerobic cocci have been reported with almost equal frequency from anaerobic bone infections. While Bacteroides fragilis is the most common anaerobe isolated in infections of other organ systems, it does not appear to be a common pathogen in anaerobic bone infections. The role of anaerobes in osteomyelitis is not yet resolved. They have been isolated in pure culture from infected bone, and under those circumstances are clearly pathogenic. Anaerobes are found more frequently as part of a mixed flora with facultative streptococci, gram-negative bacilli, and less often with S. aureus. In this setting it is unclear which organism or organisms are the primary invaders, or whether there is a synergistic mechanism of infection. The reliability of sinus drainage cultures also remains to be determined. Our retrospective study suggests that certain anaerobes isolated from sinus drainage are not present in infected bone. Cultures of bone or an abscess adjacent to bone would be expected to give more reliable data. The majority of anaerobes other than B. fragilis are susceptible to levels of penicillin achievable with parenteral administration of the antibiotic. Anaerobic pathogens should be sought in the situations noted above. We feel that parenteral penicillin should be part of the initial antibiotic regimen in patients with suspected or documented anaerobic bone infection...", "contents": "Bone infections involving anaerobic bacteria. Over 700 cases of anaerobic osteomyelitis have been reported in the literature. Nonetheless, most reviews of osteomyelitis have paid little attention to the potential role of anaerobes in bone infections. There have, as yet, been no prospective studies of osteomyelitis utlizing optimal anaerobic transport and culture techniques. In a retrospective study of osteomyelitis at Wadsworth VA Hospital from 1973--1975, 39 percent of 58 patients with osteomyelitis had an infection involving anaerobes. Anaerobes were isolated from 81 percent of 27 patients whose specimens were cultured anaerobically. Anaerobes were isolated from nine of ten samples of bone. Anaerobic bacteria were part of a mixed flora involving facultative bacteria in all but two cases. All of the patients with anaerobic infection had non-hematogenous osteomyelitis. Non-hematogenous disease comprises 80--90 percent of the osteomyelitis seen in adults. Our experience at Wadsworth VA Hospital and a review of the literature lead us to believe that anaerobes play a much larger role in osteomyelitis than has been appreciated previously. Infections of the calvarium, mastoid, mandible, maxilla and the extremities are most likely to involve anaerobes. Predisposing conditions include paranasal sinusitis, otitis media, periodontal disease, trauma, peripheral vascular disease, peripheral neuropathy and/or chronic osteomyelitis. The presence of a foul odor is a valuable clinical clue to the presence of anaerobes. Bacteroides, fusobacteria and anaerobic cocci have been reported with almost equal frequency from anaerobic bone infections. While Bacteroides fragilis is the most common anaerobe isolated in infections of other organ systems, it does not appear to be a common pathogen in anaerobic bone infections. The role of anaerobes in osteomyelitis is not yet resolved. They have been isolated in pure culture from infected bone, and under those circumstances are clearly pathogenic. Anaerobes are found more frequently as part of a mixed flora with facultative streptococci, gram-negative bacilli, and less often with S. aureus. In this setting it is unclear which organism or organisms are the primary invaders, or whether there is a synergistic mechanism of infection. The reliability of sinus drainage cultures also remains to be determined. Our retrospective study suggests that certain anaerobes isolated from sinus drainage are not present in infected bone. Cultures of bone or an abscess adjacent to bone would be expected to give more reliable data. The majority of anaerobes other than B. fragilis are susceptible to levels of penicillin achievable with parenteral administration of the antibiotic. Anaerobic pathogens should be sought in the situations noted above. We feel that parenteral penicillin should be part of the initial antibiotic regimen in patients with suspected or documented anaerobic bone infection..."}
{"id": "PMID:207947", "title": "Blood amine acid levels in patients with insulin excess (functioning insulinoma) and insulin deficiency (diabetic ketosis).", "content": "Blood amino acid concentrations were determined in the postabsorptive state in nine patients with insulin excess (functioning insulinomas), nine juvenile-type diabetics with insulin deficiency (diabetic ketosis due to insulin withdrawal), six juvenile diabetics in moderate metabolic control, and five healthy control subjects. Blood branched-chain amino acid (BCAA) levels were elevated in diabetic ketosis and decreased in patients with insulinomas. Blood concentrations of BCAA were significantly correlated to blood glucose levels, and in diabetics they were also correlated to blood ketone bodies, serum free fatty acids, and glycerol levels. These data indicate an inverse relationship between circulating effective insulin levels and blood BCAA concentrations. It is suggested that blood levels of BCAA might represent an indicator of insulin-dependent alterations of protein metabolism.", "contents": "Blood amine acid levels in patients with insulin excess (functioning insulinoma) and insulin deficiency (diabetic ketosis). Blood amino acid concentrations were determined in the postabsorptive state in nine patients with insulin excess (functioning insulinomas), nine juvenile-type diabetics with insulin deficiency (diabetic ketosis due to insulin withdrawal), six juvenile diabetics in moderate metabolic control, and five healthy control subjects. Blood branched-chain amino acid (BCAA) levels were elevated in diabetic ketosis and decreased in patients with insulinomas. Blood concentrations of BCAA were significantly correlated to blood glucose levels, and in diabetics they were also correlated to blood ketone bodies, serum free fatty acids, and glycerol levels. These data indicate an inverse relationship between circulating effective insulin levels and blood BCAA concentrations. It is suggested that blood levels of BCAA might represent an indicator of insulin-dependent alterations of protein metabolism."}
{"id": "PMID:207948", "title": "Alterations in rat renal cortical and medullary guanosine 3'5'-monophosphate accumulation by oxygen- and calcium-dependent and -independent mechanisms: evidence for a calcium-independent action of oxygen in renal inner medulla.", "content": "Factors influencing guanosine 3'5'-monophosphate (cGMP) metabolism were examined in slices of rat renal cortex, outer medulla, and inner medulla. In the presence of extracellular Ca2+ and O2, a gradation of steady-state cGMP levels was evident among the tissues (inner medulla greater than outer medulla greater than cortex). Carbamylcholine, bradykinin, histamine, and the divalent cation ionophore A23187 significantly increased cGMP in each tissue. The cGMP-stimulating action of these agents was reversibly abolished by exclusion of either Ca2+ or O2. The influence of Ca2+ and O2 on expression of effects of carbamylcholine and related cGMP agonists was interdependent in each region of the kidney, since both were required for expression of agonist action. By contrast, nitrite, nitroprusside, NH2OH, and nitrosoguanidine increased cGMP in the presence or absence of Ca2+ or O2. Thus, at least two distinct mechanisms for altering cGMP accumulation are operative or expressible in each region of the kidney: one that requires and one that does not require the presence of extracellular Ca2+ and O2. Results also suggested a role for transmembrane transport of Ca2+ in the maintenance of basal cGMP and in the expression of the responses to Ca2+-dependent agonists in renal cortex, outer and inner medulla. Thus, verapamil, which can block such transport, lowered basal cGMP and abolished these responses while ionophore A23187 enhanced cGMP in cortex and medulla only in the presence of Ca2+. The interrelationship of Ca2+ and O2 in control of basal cGMP levels clearly differed in cortex compared to inner medulla. In cortex, Ca2+ and/or O2 deprivation produced quantitatively similar reductions in cGMP. Moreover, expression of the action of O2 to increase cortical cGMP required Ca2+. Thus, O2 effects on cGMP in cortex were closely coupled with or mediated through Ca2+. By contrast, in inner medulla, O2 deprivation resulted in more pronounced reduction in basal cGMP than did Ca2+-deprivation, and O2 significantly increased inner medullary cGMP in the absence of extracellular Ca2+...", "contents": "Alterations in rat renal cortical and medullary guanosine 3'5'-monophosphate accumulation by oxygen- and calcium-dependent and -independent mechanisms: evidence for a calcium-independent action of oxygen in renal inner medulla. Factors influencing guanosine 3'5'-monophosphate (cGMP) metabolism were examined in slices of rat renal cortex, outer medulla, and inner medulla. In the presence of extracellular Ca2+ and O2, a gradation of steady-state cGMP levels was evident among the tissues (inner medulla greater than outer medulla greater than cortex). Carbamylcholine, bradykinin, histamine, and the divalent cation ionophore A23187 significantly increased cGMP in each tissue. The cGMP-stimulating action of these agents was reversibly abolished by exclusion of either Ca2+ or O2. The influence of Ca2+ and O2 on expression of effects of carbamylcholine and related cGMP agonists was interdependent in each region of the kidney, since both were required for expression of agonist action. By contrast, nitrite, nitroprusside, NH2OH, and nitrosoguanidine increased cGMP in the presence or absence of Ca2+ or O2. Thus, at least two distinct mechanisms for altering cGMP accumulation are operative or expressible in each region of the kidney: one that requires and one that does not require the presence of extracellular Ca2+ and O2. Results also suggested a role for transmembrane transport of Ca2+ in the maintenance of basal cGMP and in the expression of the responses to Ca2+-dependent agonists in renal cortex, outer and inner medulla. Thus, verapamil, which can block such transport, lowered basal cGMP and abolished these responses while ionophore A23187 enhanced cGMP in cortex and medulla only in the presence of Ca2+. The interrelationship of Ca2+ and O2 in control of basal cGMP levels clearly differed in cortex compared to inner medulla. In cortex, Ca2+ and/or O2 deprivation produced quantitatively similar reductions in cGMP. Moreover, expression of the action of O2 to increase cortical cGMP required Ca2+. Thus, O2 effects on cGMP in cortex were closely coupled with or mediated through Ca2+. By contrast, in inner medulla, O2 deprivation resulted in more pronounced reduction in basal cGMP than did Ca2+-deprivation, and O2 significantly increased inner medullary cGMP in the absence of extracellular Ca2+..."}
{"id": "PMID:207952", "title": "Immunological studies of heat-labile virus inhibitors. I. Specificity of absorption onto sensitive viruses and specific response after virus infections.", "content": "Heat-labile virus inhibitor (HLI) in normal sera of various mammalian species capable of neutralizing variola (VRV) and Newcastle disease viruses (NDV) was studied immunologically. After sucrose density gradient centrifugation of guinea pig serum, the HLI activity against VRV and that against NDV were both demonstrated in the same region sedimenting fastor than IgM. Absorption with partially purified VRV or NDV removed the HLI activity on the homologous virus but not that on the other. Prior saturation of virions with specific antibody blocked the absorption of HLI, suggesting a specific competition for binding site (s) between specific antibody and HLI. The HLI level against variola virus was checked in connection with immunization with vaccinia virus. In human primary vaccination, the HLI level rose sharply within 4 weeks after vaccination, turning to decline gradually to settle at a level higher than that of the conventional neutralizing antibody (NA). In cases of human revaccination, a sharp rise of HLI started 4 days after vaccination and reached the highest level within 7 days, preceding the rise of conventional NA level which occurred about 3 days later. Three rabbits with negative HLI activity prior to vaccinia immunization obtained an HLI activity within 2 weeks, which showed a sharp rise up to 6-8 weeks. One rabbit with a positive prior HLI activity also showed a sharp rise of the HLI activity after immunization. In all rabbits the final HLI level was identical with that of conventional NA. Groups of guinea pigs were immunized with either VRV or NDV. Rises of the HLI level after immunization were observed in all animals, the activity being restricted to the homologous virus used in the immunization. Complement requiring NA was detected during the course of immunization but its behavior was different from that of HLI. The above observations were interpreted to suggest a ubiquitous presence of HLI as a specific reactive agent and its role at an earliest stage of immune response.", "contents": "Immunological studies of heat-labile virus inhibitors. I. Specificity of absorption onto sensitive viruses and specific response after virus infections. Heat-labile virus inhibitor (HLI) in normal sera of various mammalian species capable of neutralizing variola (VRV) and Newcastle disease viruses (NDV) was studied immunologically. After sucrose density gradient centrifugation of guinea pig serum, the HLI activity against VRV and that against NDV were both demonstrated in the same region sedimenting fastor than IgM. Absorption with partially purified VRV or NDV removed the HLI activity on the homologous virus but not that on the other. Prior saturation of virions with specific antibody blocked the absorption of HLI, suggesting a specific competition for binding site (s) between specific antibody and HLI. The HLI level against variola virus was checked in connection with immunization with vaccinia virus. In human primary vaccination, the HLI level rose sharply within 4 weeks after vaccination, turning to decline gradually to settle at a level higher than that of the conventional neutralizing antibody (NA). In cases of human revaccination, a sharp rise of HLI started 4 days after vaccination and reached the highest level within 7 days, preceding the rise of conventional NA level which occurred about 3 days later. Three rabbits with negative HLI activity prior to vaccinia immunization obtained an HLI activity within 2 weeks, which showed a sharp rise up to 6-8 weeks. One rabbit with a positive prior HLI activity also showed a sharp rise of the HLI activity after immunization. In all rabbits the final HLI level was identical with that of conventional NA. Groups of guinea pigs were immunized with either VRV or NDV. Rises of the HLI level after immunization were observed in all animals, the activity being restricted to the homologous virus used in the immunization. Complement requiring NA was detected during the course of immunization but its behavior was different from that of HLI. The above observations were interpreted to suggest a ubiquitous presence of HLI as a specific reactive agent and its role at an earliest stage of immune response."}
{"id": "PMID:207954", "title": "A survey of rotavirus associated with gastroenteritis in Aboriginal children in Western Australia.", "content": "In a year-long survey which was carried out between April, 1975, and March, 1976, faecal specimens from Aboriginal and some non-Aboriginal children who suffered from gastroenteritis were examined by electron microscopy for rotavirus, and also tested for bacteria and parasites. The children were under six years of age and came from all parts of Western Australia, except Perth. Rotaviruses, \"astroviruses\" and adenoviruses were detected as well as the usual potentially pathogenic bacteria and parasites. Two peaks of rotavirus incidence were found during the year in specimens from Kalgoorlie, but only one peak occurred in Derby. Rotavirus was somewhat more frequently seen in non-Aboriginal than Aboriginal children.", "contents": "A survey of rotavirus associated with gastroenteritis in Aboriginal children in Western Australia. In a year-long survey which was carried out between April, 1975, and March, 1976, faecal specimens from Aboriginal and some non-Aboriginal children who suffered from gastroenteritis were examined by electron microscopy for rotavirus, and also tested for bacteria and parasites. The children were under six years of age and came from all parts of Western Australia, except Perth. Rotaviruses, \"astroviruses\" and adenoviruses were detected as well as the usual potentially pathogenic bacteria and parasites. Two peaks of rotavirus incidence were found during the year in specimens from Kalgoorlie, but only one peak occurred in Derby. Rotavirus was somewhat more frequently seen in non-Aboriginal than Aboriginal children."}
{"id": "PMID:207959", "title": "[Treatment of hyperlipoproteinemia type IIa with a \"prudent\" diet and clofibrate (author's transl)].", "content": "14 previously untreated patients with hyperlipoproteinemia type IIa according to Fredrickson underwent a controlled clinical trial. The study was designed to clarify the effects of clofibrate on the bloodlipids. All patients were willing to cooperate. After leaving their usual dietary habits all of them were given for seven to ten days a \"prudent\" diet. This diet was rich in vitamins; it had a low caloric-content. 20% of the calories consisted of proteins, 35% of carbohydrates (sweets were omitted) and about 45% of fats with a PS-factor of about 2.2. After the initial dietary treatment all patients were given twice daily for 14 days 500 mg clofibrate. During the use of the \"prudent\" diet the serum-cholesterol-levels decreased in average with 14.8%. Compared to the values at the beginning of the trial the difference was statistically highly significant. The average-values of triglycerides, phosphatides and the relative percentage of HDL, LDL and VLDL remained unchanged. After the patients received clofibrate there was an additional decrease of the serum-cholesterol-values of 14.8%. The total decrease of the cholesterol-levels compared to the initial values amounted to 27.4%. Furthermore, there was a reduction of the phosphatids in the serum of 14.1% compared to the initial value and of 9.9% compared to the value after dietary treatment alone. Under the combined effects of a \"prudent\" diet with clofibrate the HDL increased significantly. It can be assumed that clofibrate reduces the serum-cholesterol-levels in cases of hyperlipoproteinemia by decreasing the LDL-fraction, which is rich in cholesterol, and by increasing the HDL-fraction.", "contents": "[Treatment of hyperlipoproteinemia type IIa with a \"prudent\" diet and clofibrate (author's transl)]. 14 previously untreated patients with hyperlipoproteinemia type IIa according to Fredrickson underwent a controlled clinical trial. The study was designed to clarify the effects of clofibrate on the bloodlipids. All patients were willing to cooperate. After leaving their usual dietary habits all of them were given for seven to ten days a \"prudent\" diet. This diet was rich in vitamins; it had a low caloric-content. 20% of the calories consisted of proteins, 35% of carbohydrates (sweets were omitted) and about 45% of fats with a PS-factor of about 2.2. After the initial dietary treatment all patients were given twice daily for 14 days 500 mg clofibrate. During the use of the \"prudent\" diet the serum-cholesterol-levels decreased in average with 14.8%. Compared to the values at the beginning of the trial the difference was statistically highly significant. The average-values of triglycerides, phosphatides and the relative percentage of HDL, LDL and VLDL remained unchanged. After the patients received clofibrate there was an additional decrease of the serum-cholesterol-values of 14.8%. The total decrease of the cholesterol-levels compared to the initial values amounted to 27.4%. Furthermore, there was a reduction of the phosphatids in the serum of 14.1% compared to the initial value and of 9.9% compared to the value after dietary treatment alone. Under the combined effects of a \"prudent\" diet with clofibrate the HDL increased significantly. It can be assumed that clofibrate reduces the serum-cholesterol-levels in cases of hyperlipoproteinemia by decreasing the LDL-fraction, which is rich in cholesterol, and by increasing the HDL-fraction."}
{"id": "PMID:207960", "title": "[Intestinal yersiniosis: 25 cases of infections with Yersinia pseudotuberculosis and Yersinia enterocolitica (author's transl)].", "content": "Yersinia infections in 16 adults and 9 children are reported. 15 cases were caused by Yersinia pseudotuberculosis, 8 of them were proved by serological findings. In 4 cases the infection by Yersinia pseudotuberculosis was likely, in 3 other cases possible only. Real infections caused by serotype IV are demonstrated too. Furthermore there were 10 cases caused by Yersinia enterocolitica, 3 of them were proved by bacterial, the other ones by serological findings. Both germs caused identical symptoms: fever (80%), abdominal pains (56%), diarrhoea (52%), erythema nodosum (44%), arthritis (40%), vomiting (16%), weight loss (16%), lymphoma (12%) and others. In children 50% of erythema nodosum was produced by intestinal yersiniosis. The beginning with gastroenteritis and fever mostly was followed by a second phase with returning fever, abdominal pains, erythema nodosum and/or arthritis. Antibiotic therapy had a definite effect only in the first phase of gastroenteritis and in the two possibly relapsing cases. In two of 5 patients with long standing arthritis the HL-AB 27 was present.", "contents": "[Intestinal yersiniosis: 25 cases of infections with Yersinia pseudotuberculosis and Yersinia enterocolitica (author's transl)]. Yersinia infections in 16 adults and 9 children are reported. 15 cases were caused by Yersinia pseudotuberculosis, 8 of them were proved by serological findings. In 4 cases the infection by Yersinia pseudotuberculosis was likely, in 3 other cases possible only. Real infections caused by serotype IV are demonstrated too. Furthermore there were 10 cases caused by Yersinia enterocolitica, 3 of them were proved by bacterial, the other ones by serological findings. Both germs caused identical symptoms: fever (80%), abdominal pains (56%), diarrhoea (52%), erythema nodosum (44%), arthritis (40%), vomiting (16%), weight loss (16%), lymphoma (12%) and others. In children 50% of erythema nodosum was produced by intestinal yersiniosis. The beginning with gastroenteritis and fever mostly was followed by a second phase with returning fever, abdominal pains, erythema nodosum and/or arthritis. Antibiotic therapy had a definite effect only in the first phase of gastroenteritis and in the two possibly relapsing cases. In two of 5 patients with long standing arthritis the HL-AB 27 was present."}
{"id": "PMID:207962", "title": "Hepatocellular carcinoma in a young woman with prolonged exposure to oral contraceptives.", "content": "A case of hepatocellular carcinoma in a young female is presented in which the apparent etiology was the use of oral contraceptives for 5 1/2 years. Sequential therapeutic trials with intraarterial 5-fluorouracil, intraarterial adriamycin, and intravenous 1,3 bis[2-chloroethyl]-1-nitrosourea (BCNU) were unsuccesful. The adverse effects of oral contraceptives on the structure and function of hepatic tissue are reviewed.", "contents": "Hepatocellular carcinoma in a young woman with prolonged exposure to oral contraceptives. A case of hepatocellular carcinoma in a young female is presented in which the apparent etiology was the use of oral contraceptives for 5 1/2 years. Sequential therapeutic trials with intraarterial 5-fluorouracil, intraarterial adriamycin, and intravenous 1,3 bis[2-chloroethyl]-1-nitrosourea (BCNU) were unsuccesful. The adverse effects of oral contraceptives on the structure and function of hepatic tissue are reviewed."}
{"id": "PMID:207964", "title": "[Reactions of the submandibular salivary gland caused by sialography. Experimental research in dogs].", "content": "In order to ascertain the damaging effects on the glandular parenchyma and excretory system of the major salivary glands of sialography using iodate contrast media in an oily vehicle, experiments have been carried out on a group of dogs. Among other compounds, Lipiodol UF and Urovison were used, the former oil-based and the latter water-based. Histological slides of the injected gland made three and four weeks afterwards showed in one animal only the presence of a periductal infiltrate and an intracanalicular formation of hyaline thrombotic type that was not easy to interpret. Lipiodol UF was employed in this case. Comparing these results with the literature, it is concluded that Lipiodol is an irritant, especially if it passes beyond the salivary excretory tree, but this is not enough to have it banned absolutely. Contraindications are reported and the need for correct technique stressed.", "contents": "[Reactions of the submandibular salivary gland caused by sialography. Experimental research in dogs]. In order to ascertain the damaging effects on the glandular parenchyma and excretory system of the major salivary glands of sialography using iodate contrast media in an oily vehicle, experiments have been carried out on a group of dogs. Among other compounds, Lipiodol UF and Urovison were used, the former oil-based and the latter water-based. Histological slides of the injected gland made three and four weeks afterwards showed in one animal only the presence of a periductal infiltrate and an intracanalicular formation of hyaline thrombotic type that was not easy to interpret. Lipiodol UF was employed in this case. Comparing these results with the literature, it is concluded that Lipiodol is an irritant, especially if it passes beyond the salivary excretory tree, but this is not enough to have it banned absolutely. Contraindications are reported and the need for correct technique stressed."}
{"id": "PMID:207973", "title": "Biosynthesis of mitochondrial membrane proteins: co-ordination with special reference to cytochrome c oxidase.", "content": "This paper reviews mechanisms by which the rate of synthesis of subunits of mitochondrial inner membrane protein complexes and the assembly of these subunits are co-ordinated. Current models are evaluated and critically discussed in the light of some recent evidences. The focus is on the incorporation of cytoplasmically-synthesized cytochrome c oxidase subunits in the development of a newer model, which introduces some twists into a combination of several current ideas. A mechanism which governs both organized assembly and the co-ordination of rates of polypeptide synthesis is illustrated and the principles of the model are applied to the elucidation of some odd features of certain mutants. The possibilities that mitochondrial ATPase and cytochrome c reductase may also be synthesized and assembled according to this model are discussed.", "contents": "Biosynthesis of mitochondrial membrane proteins: co-ordination with special reference to cytochrome c oxidase. This paper reviews mechanisms by which the rate of synthesis of subunits of mitochondrial inner membrane protein complexes and the assembly of these subunits are co-ordinated. Current models are evaluated and critically discussed in the light of some recent evidences. The focus is on the incorporation of cytoplasmically-synthesized cytochrome c oxidase subunits in the development of a newer model, which introduces some twists into a combination of several current ideas. A mechanism which governs both organized assembly and the co-ordination of rates of polypeptide synthesis is illustrated and the principles of the model are applied to the elucidation of some odd features of certain mutants. The possibilities that mitochondrial ATPase and cytochrome c reductase may also be synthesized and assembled according to this model are discussed."}
{"id": "PMID:207974", "title": "Steady-state study of horse-liver ADH: detection of two kinetically heterogeneous components.", "content": "New theoretical considerations and a new approximation strategy were applied to the kinetic analysis of the experimental relationship between the reaction velocity in the steady state and the concentrations of ethanol and NAD. It could be shown that horse-liver ADH consists of two kinetically heterogeneous components.", "contents": "Steady-state study of horse-liver ADH: detection of two kinetically heterogeneous components. New theoretical considerations and a new approximation strategy were applied to the kinetic analysis of the experimental relationship between the reaction velocity in the steady state and the concentrations of ethanol and NAD. It could be shown that horse-liver ADH consists of two kinetically heterogeneous components."}
{"id": "PMID:207975", "title": "[Study of the conformational mobility of globular proteins by pulse methods of NMR].", "content": "The protein spin-echo decay and recovery of longitudinal magnetization were studied in seven globular proteins: cytochrome C, ribonuclease, lysozyme, DNA, hemoglobin, serum albumin and gamma-globulin in D2O solutions. For comparison the Tobacco mosaic virus (TMV) protons in D2O solutions were also investigated. The spin-echo decay of all 7 proteins can be separated into three components: a slowly decaying component with an amplitude of about 10% of the amplitude of the total signal, intermediately and fastly decaying components, the two latter being comparable in amplitudes. Longitudinal relaxation is more simple in character. The value of T2 of the protons responsible for the fastly decaying components in linearly dependent on the molecular weight of the protein, a fact indicating that the regions of the proteins with a \"rigid\" structure can be responsible for this component. The intermediate component, whose contribution increases with temperature, was ascribed to the mobile regions of the protein, and the slowly decaying component to the mobile protein side chains. Weak dependence of T1 on the protein molecular weight and some other obtained data give additional evidence for the presence of motion within macromolecules. The peculiarities of this motion is in good correspondence with the notion about the existence of the segmental motion of the polypeptide chain (conformational mobility of the protein). In contrast to proteins the spin-echo decay of TMV lacked the slow component and the \"solid\" echo signal was observed which indicates the existence of a \"rigid\" structure in the macromolecules of the virus.", "contents": "[Study of the conformational mobility of globular proteins by pulse methods of NMR]. The protein spin-echo decay and recovery of longitudinal magnetization were studied in seven globular proteins: cytochrome C, ribonuclease, lysozyme, DNA, hemoglobin, serum albumin and gamma-globulin in D2O solutions. For comparison the Tobacco mosaic virus (TMV) protons in D2O solutions were also investigated. The spin-echo decay of all 7 proteins can be separated into three components: a slowly decaying component with an amplitude of about 10% of the amplitude of the total signal, intermediately and fastly decaying components, the two latter being comparable in amplitudes. Longitudinal relaxation is more simple in character. The value of T2 of the protons responsible for the fastly decaying components in linearly dependent on the molecular weight of the protein, a fact indicating that the regions of the proteins with a \"rigid\" structure can be responsible for this component. The intermediate component, whose contribution increases with temperature, was ascribed to the mobile regions of the protein, and the slowly decaying component to the mobile protein side chains. Weak dependence of T1 on the protein molecular weight and some other obtained data give additional evidence for the presence of motion within macromolecules. The peculiarities of this motion is in good correspondence with the notion about the existence of the segmental motion of the polypeptide chain (conformational mobility of the protein). In contrast to proteins the spin-echo decay of TMV lacked the slow component and the \"solid\" echo signal was observed which indicates the existence of a \"rigid\" structure in the macromolecules of the virus."}
{"id": "PMID:207976", "title": "[Spin label study of the surface of lipid bilayers].", "content": "The surface of liposomes and natural membranes has been studied by the method of \"spin label--spin probe\". Various nitroxyl radicals have been attached to membranes either dueto covalent binding with NH2-groups of phosphatidylethanolamine or due to hydrophobic interactions. Addition of paramagnetics of different charge signs (potassium ferricyanide and dibenzenechromium iodide) to spin labeled membranes results in a decrease of the EPR line intensity without marked broadening. Since the paramagnetic is attached to the membrane surface near the label it broadens the label's EPR spectrum so that it can not be observed. In this case one can observe only the spectrum of labels which have no paramagnetics in the vicinity, the nitroxyl part of radicals being inaccessible to direct paramagnetic impacts. The constants of binding of paramagnetics to the membrane surface have been determined from these experiments. All results (including the assymetry of label rotation) can be explained most simply by assuming that the polar lipid groups are oriented parallel to the membranes surface.", "contents": "[Spin label study of the surface of lipid bilayers]. The surface of liposomes and natural membranes has been studied by the method of \"spin label--spin probe\". Various nitroxyl radicals have been attached to membranes either dueto covalent binding with NH2-groups of phosphatidylethanolamine or due to hydrophobic interactions. Addition of paramagnetics of different charge signs (potassium ferricyanide and dibenzenechromium iodide) to spin labeled membranes results in a decrease of the EPR line intensity without marked broadening. Since the paramagnetic is attached to the membrane surface near the label it broadens the label's EPR spectrum so that it can not be observed. In this case one can observe only the spectrum of labels which have no paramagnetics in the vicinity, the nitroxyl part of radicals being inaccessible to direct paramagnetic impacts. The constants of binding of paramagnetics to the membrane surface have been determined from these experiments. All results (including the assymetry of label rotation) can be explained most simply by assuming that the polar lipid groups are oriented parallel to the membranes surface."}
{"id": "PMID:207981", "title": "Comparative mutagenicity of alkylsulfate and alkanesulfonate derivatives in Chinese hamster ovary cells.", "content": "Mutation induction and cell killing produced by selected alkylsulfates and alkanesulfonates have been quantitated using the Chinese hamster ovary/hypoxanthine--guanine phosphoribosyl transferase (CHO/HGPRT) system. Dose--response relationships of cytotoxicity and mutagenicity are presented for two alkylsulfates [dimethylsulfate (DMS), diethylsulfate (DES)] and three alkyl alkanesulfonates [methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), and isopropyl methanesulfonate (iPMS)]. Under the experimental conditions employed, cytotoxicity decreased with the size of the alkyl group. DMS was more toxic than DES, and MMS was more toxic than EMS and iPMS. All agents produced linear dose--response of mutation induction: DMS was more mutagenic than DES, and MMS was more mutagenic than EMS and iPMS based on mutants induced per unit mutagen concentration. However, the following relative mutagenic potency was observed when comparisons were made at 10% survival: DES greater than DMS; EMS greater than MMS greater than iPMS.", "contents": "Comparative mutagenicity of alkylsulfate and alkanesulfonate derivatives in Chinese hamster ovary cells. Mutation induction and cell killing produced by selected alkylsulfates and alkanesulfonates have been quantitated using the Chinese hamster ovary/hypoxanthine--guanine phosphoribosyl transferase (CHO/HGPRT) system. Dose--response relationships of cytotoxicity and mutagenicity are presented for two alkylsulfates [dimethylsulfate (DMS), diethylsulfate (DES)] and three alkyl alkanesulfonates [methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), and isopropyl methanesulfonate (iPMS)]. Under the experimental conditions employed, cytotoxicity decreased with the size of the alkyl group. DMS was more toxic than DES, and MMS was more toxic than EMS and iPMS. All agents produced linear dose--response of mutation induction: DMS was more mutagenic than DES, and MMS was more mutagenic than EMS and iPMS based on mutants induced per unit mutagen concentration. However, the following relative mutagenic potency was observed when comparisons were made at 10% survival: DES greater than DMS; EMS greater than MMS greater than iPMS."}
{"id": "PMID:207977", "title": "[Tryptophanyl tRNA synthetase: isolation and characteristics of the tryptophanyl-enzyme].", "content": "The catalytic groups, involved in aminoacyl-tRNA formation remain unknown. The isolation and identification of an active covalent complex between the enzyme and substrate is an essential step in understanding the reaction mechanism. We identified and isolated the covalent complex of tryptophanyl-tRNA synthetase (EC 6.1.1.2) and tryptophane which was able to aminoacylate the tRNATrp in the absence of ATP. In beef pancreas tryptophanyl-tRNA synthetase preparations, isolated by the previously described method, a tightly bound tryptophan was revealed which could not be removed by charcoal treatment, by gel-filtration and by replacement with the excess of typtamine, a competitive inhibitor of tryptophane. This tightly bound tryptophane is able to exchange rapidly and specifically with radioactive tryptophane allowing to obtain [14C]tryptophane-tryptophanyl-tRNA synthetase complex. After the reaction of this complex with NH2OH at neutral pH tryptophanyl hydroxamate is formed proving the activated state of the tryptophane in the initial complex with the enzyme. No nucleotide impurites were noticed in the enzyme preparation; the complex is stable at denaturation. A conclusion is made that the tryptophanyl-tRNA synthetase isolated by our method is a tryptophanyl-enzyme. The tryptophanyl residue could be specifically transferred to tRNATrp in the absence of other substrates of the reaction, the efficiency of the transfer does not exceed 25%. The content of the covalently bound tryptophane never exceeds 1 mole per mole of the dimeric enzyme. The total content of tryptophane in the forms of tryptophanyl-enzyme and tryptophanyl adenylate enzyme complex equals 2 moles per mole of the enzyme. The tryptophanyl-enzyme is destroyed during incubation with AMP or with pyrophosphate. The role of the tryptophanyl-enzyme as a possible intermediate in the course of aminoacylation of tRNATrp is discussed.", "contents": "[Tryptophanyl tRNA synthetase: isolation and characteristics of the tryptophanyl-enzyme]. The catalytic groups, involved in aminoacyl-tRNA formation remain unknown. The isolation and identification of an active covalent complex between the enzyme and substrate is an essential step in understanding the reaction mechanism. We identified and isolated the covalent complex of tryptophanyl-tRNA synthetase (EC 6.1.1.2) and tryptophane which was able to aminoacylate the tRNATrp in the absence of ATP. In beef pancreas tryptophanyl-tRNA synthetase preparations, isolated by the previously described method, a tightly bound tryptophan was revealed which could not be removed by charcoal treatment, by gel-filtration and by replacement with the excess of typtamine, a competitive inhibitor of tryptophane. This tightly bound tryptophane is able to exchange rapidly and specifically with radioactive tryptophane allowing to obtain [14C]tryptophane-tryptophanyl-tRNA synthetase complex. After the reaction of this complex with NH2OH at neutral pH tryptophanyl hydroxamate is formed proving the activated state of the tryptophane in the initial complex with the enzyme. No nucleotide impurites were noticed in the enzyme preparation; the complex is stable at denaturation. A conclusion is made that the tryptophanyl-tRNA synthetase isolated by our method is a tryptophanyl-enzyme. The tryptophanyl residue could be specifically transferred to tRNATrp in the absence of other substrates of the reaction, the efficiency of the transfer does not exceed 25%. The content of the covalently bound tryptophane never exceeds 1 mole per mole of the dimeric enzyme. The total content of tryptophane in the forms of tryptophanyl-enzyme and tryptophanyl adenylate enzyme complex equals 2 moles per mole of the enzyme. The tryptophanyl-enzyme is destroyed during incubation with AMP or with pyrophosphate. The role of the tryptophanyl-enzyme as a possible intermediate in the course of aminoacylation of tRNATrp is discussed."}
{"id": "PMID:207982", "title": "Sister chromatid exchange studies for monitoring DNA damage and repair capacity after cytostatics in vitro and in lymphocytes of leukaemic patients under cytostatic therapy.", "content": "The effect of various cytostatic drugs was studied on the frequency of sister chromatid exchanges (SCEs) in vitro and in PHA-stimulated lymphocytes of leukaemic patients under cytostatic therapy. The lymphocyte system is a sensitive one for the detection of DNA damage after administration of cytostatic drugs in vitro. Mitomycin C, busulphan, vincristine, chlorambucil, cytosine arabinoside, cyclophosphamide and lycurim were tested. All except cyclophosphamide induced high frequencies of SCEs in the first mitosis after their administration. The experiments with PHA-stimulated lymphocytes in vivo from patients treated with cytostatics showed that cytosine arabinoside, in combination with thioguanine, did not induce higher frequencies of SCEs, whereas in patients who were treated with cyclophosphamide alone or in combination with other cytostatic drugs, there was a higher incidence of SCEs during treatment. About 10 days after the termination of the treatment the elevated freuqencies of SCEs returned to the initial level. After administration of some mutagens, especially alkylating agents in vivo, the lymphocyte system can be used to assess induced DNA repair by continuously monitoring for SCEs.", "contents": "Sister chromatid exchange studies for monitoring DNA damage and repair capacity after cytostatics in vitro and in lymphocytes of leukaemic patients under cytostatic therapy. The effect of various cytostatic drugs was studied on the frequency of sister chromatid exchanges (SCEs) in vitro and in PHA-stimulated lymphocytes of leukaemic patients under cytostatic therapy. The lymphocyte system is a sensitive one for the detection of DNA damage after administration of cytostatic drugs in vitro. Mitomycin C, busulphan, vincristine, chlorambucil, cytosine arabinoside, cyclophosphamide and lycurim were tested. All except cyclophosphamide induced high frequencies of SCEs in the first mitosis after their administration. The experiments with PHA-stimulated lymphocytes in vivo from patients treated with cytostatics showed that cytosine arabinoside, in combination with thioguanine, did not induce higher frequencies of SCEs, whereas in patients who were treated with cyclophosphamide alone or in combination with other cytostatic drugs, there was a higher incidence of SCEs during treatment. About 10 days after the termination of the treatment the elevated freuqencies of SCEs returned to the initial level. After administration of some mutagens, especially alkylating agents in vivo, the lymphocyte system can be used to assess induced DNA repair by continuously monitoring for SCEs."}
{"id": "PMID:207978", "title": "[Endogenous DNA synthesis in isolated chromatin].", "content": "It was shown that chromatin isolated from the liver of adult rats is an effective cell-free system for studying DNA synthesis without using exogenous enzymes or DNA-template. Both replication synthesis initiated in vivo and unscheduled synthesis activated several fold after gamma-irradiation of isolated chromatin proceed in chromatin preparations. Unscheduled synthesis consists of template-dependent and template-independent synthesis. Template-dependent synthesis proceeds with a maximum rate in the presence of all four deoxynucleoside triphosphates (dNTP). Template-independent synthesis proceeds with an appearable maximum rate in the presence of one dNTP whose incorporation is inhibited by the addition of the rest dNTP. All three DNA synthesis in chromatin are ATP-dependent. Replication synthesis but not the unscheduled one is inhibited by actinomycin D and N-ethylmaleinimide. Repair inhibitor--0.01 M caffeine--suppresses the initiation of unscheduled synthesis, but does not influence its elongation. The incubation conditions of chromatin for unscheduled synthesis are optimalized as for temperature, pH, time of incubation, qualitative ionic composition of the medium, concentration of chromatin, ATP, dNTP, MgCl2, NaCl. Michaelis constants for TTP are equal to 1 mM for template-independent synthesis and 3 mM for template-dependent synthesis. At optimal conditions DNA  of chromatin is lengthened by 8 X 10--3% as the result of template-dependent synthesis and by 1 X 10--3% as the result of template-independent. The transition from nuclei to chromatin as well as the purification of chromatin from nuclear membranes enhance the rate of unscheduled synthesis. On the other hand, addition of nucleoplasm or cell extract to the chromatin does not considerably influence the synthesis. So it is suggested that the enzymes of initiation and elongation of unscheduled DNA synthesis are concentrated in the chromatin. The plausible role of unscheduled synthesis in excision and postreplication repair of eukaryotic DNA is discussed.", "contents": "[Endogenous DNA synthesis in isolated chromatin]. It was shown that chromatin isolated from the liver of adult rats is an effective cell-free system for studying DNA synthesis without using exogenous enzymes or DNA-template. Both replication synthesis initiated in vivo and unscheduled synthesis activated several fold after gamma-irradiation of isolated chromatin proceed in chromatin preparations. Unscheduled synthesis consists of template-dependent and template-independent synthesis. Template-dependent synthesis proceeds with a maximum rate in the presence of all four deoxynucleoside triphosphates (dNTP). Template-independent synthesis proceeds with an appearable maximum rate in the presence of one dNTP whose incorporation is inhibited by the addition of the rest dNTP. All three DNA synthesis in chromatin are ATP-dependent. Replication synthesis but not the unscheduled one is inhibited by actinomycin D and N-ethylmaleinimide. Repair inhibitor--0.01 M caffeine--suppresses the initiation of unscheduled synthesis, but does not influence its elongation. The incubation conditions of chromatin for unscheduled synthesis are optimalized as for temperature, pH, time of incubation, qualitative ionic composition of the medium, concentration of chromatin, ATP, dNTP, MgCl2, NaCl. Michaelis constants for TTP are equal to 1 mM for template-independent synthesis and 3 mM for template-dependent synthesis. At optimal conditions DNA  of chromatin is lengthened by 8 X 10--3% as the result of template-dependent synthesis and by 1 X 10--3% as the result of template-independent. The transition from nuclei to chromatin as well as the purification of chromatin from nuclear membranes enhance the rate of unscheduled synthesis. On the other hand, addition of nucleoplasm or cell extract to the chromatin does not considerably influence the synthesis. So it is suggested that the enzymes of initiation and elongation of unscheduled DNA synthesis are concentrated in the chromatin. The plausible role of unscheduled synthesis in excision and postreplication repair of eukaryotic DNA is discussed."}
{"id": "PMID:207979", "title": "[Polarity of the environment as a factor determining DNA conformation].", "content": "Polarity of double and ternary water-nonelectrolyte systems at the component ratio, corresponding to a half-transition point of DNA from B to A form was evaluated from ESR spectra of a spin-probe. In all cases examined the isotropic super-fine splitting constant (aN) is the same with an accuracy of 0.05 gauss. Small differences in aN are well correlated with the concentration of the groups which are able to form hydrogen bonds with the nitroxide fragment of the radical. Thus, media polarity is a factor which determines the A--B equilibrium of DNA in solution.", "contents": "[Polarity of the environment as a factor determining DNA conformation]. Polarity of double and ternary water-nonelectrolyte systems at the component ratio, corresponding to a half-transition point of DNA from B to A form was evaluated from ESR spectra of a spin-probe. In all cases examined the isotropic super-fine splitting constant (aN) is the same with an accuracy of 0.05 gauss. Small differences in aN are well correlated with the concentration of the groups which are able to form hydrogen bonds with the nitroxide fragment of the radical. Thus, media polarity is a factor which determines the A--B equilibrium of DNA in solution."}
{"id": "PMID:207983", "title": "Serum high-density-lipoprotein cholesterol in women using oral contraceptives, estrogens and progestins.", "content": "To determine the associations between high-density-lipoprotein cholesterol levels and use of oral contraceptives or of noncontraceptive estrogens and progestins we analyzed the serum levels of this lipid in 4978 women, 21 to 62 years of age. In estrogen users, the mean level was 6.7 to 15.1 mg per deciliter above the nonuser level (P less than 0.001), whereas in a group of progestin users it was 15.8 mg per deciliter below (P less than 0.001). In women using combination oral contraceptives, the level varied with the type and dose of the component steroids, in general increasing with increasing dose of estrogen and decreasing with increasing dose or potency of progestin. Thus, the net effect of use of a combination oral contraceptive on high-density-lipoprotein cholesterol depends on its formulation.", "contents": "Serum high-density-lipoprotein cholesterol in women using oral contraceptives, estrogens and progestins. To determine the associations between high-density-lipoprotein cholesterol levels and use of oral contraceptives or of noncontraceptive estrogens and progestins we analyzed the serum levels of this lipid in 4978 women, 21 to 62 years of age. In estrogen users, the mean level was 6.7 to 15.1 mg per deciliter above the nonuser level (P less than 0.001), whereas in a group of progestin users it was 15.8 mg per deciliter below (P less than 0.001). In women using combination oral contraceptives, the level varied with the type and dose of the component steroids, in general increasing with increasing dose of estrogen and decreasing with increasing dose or potency of progestin. Thus, the net effect of use of a combination oral contraceptive on high-density-lipoprotein cholesterol depends on its formulation."}
{"id": "PMID:207985", "title": "Argentine hemorrhagic fever. Alterations of the complement system and anti-Junin-virus humoral response.", "content": "We investigated immunologic mechanisms and the role of complement in the pathogenesis of Argentine hemorrhagic fever, a disease caused by the Junin virus, a member of the arenavirus group. Total serum complement activity was reduced to 68 per cent of control values in patients with severe or moderate disease (P less than 0.001). C2, C3 and C5 values were also low (12 to 60 per cent) during the early acute period of the disease. However, serum C4 content was increased to 160 per cent of the control values in the same patients. Total complement activity returned to normal with clinical and laboratory recovery, at the time of detection of antibodies against Junin virus. C1q reactive material was found in four of 19 cases and no relation to the evolution of the disease could be established. These results suggest that immune complexes are not important in the pathogenesis of Argentine hemorrhagic fever, but that activation of the complement system has a role.", "contents": "Argentine hemorrhagic fever. Alterations of the complement system and anti-Junin-virus humoral response. We investigated immunologic mechanisms and the role of complement in the pathogenesis of Argentine hemorrhagic fever, a disease caused by the Junin virus, a member of the arenavirus group. Total serum complement activity was reduced to 68 per cent of control values in patients with severe or moderate disease (P less than 0.001). C2, C3 and C5 values were also low (12 to 60 per cent) during the early acute period of the disease. However, serum C4 content was increased to 160 per cent of the control values in the same patients. Total complement activity returned to normal with clinical and laboratory recovery, at the time of detection of antibodies against Junin virus. C1q reactive material was found in four of 19 cases and no relation to the evolution of the disease could be established. These results suggest that immune complexes are not important in the pathogenesis of Argentine hemorrhagic fever, but that activation of the complement system has a role."}
{"id": "PMID:207986", "title": "Dysfibrinogenemia associated with hepatoma. Increased carbohydrate content of the fibrinogen molecule.", "content": "Abnormal coagulation studies indicative of a dysfibrinogen were found in the plasma of four of seven patients with malignant hepatoma. The abnormal fibrinogen was characterized by prolonged prothrombin, thrombin and reptilase times and inhibition of the coagulation of normal plasma. Purified fibrinogen revealed abnormalities similar to those in plasma. The functional defect was one of delayed polymerization of the fibrin monomer. The carbohydrate content of the abnormal fibrinogen was increased, and this change was related to the abnormal fibrinogen function. Enzymatic cleavage of sialic acid from the abnormal fibrinogen restored fibrinogen function to normal. This hepatoma-associated dysfibrinogen (acquired dysfibrinogenemia) is similar in many respects to fetal fibrinogen and may represent the presence of a fetal form of fibrinogen in hepatoma.", "contents": "Dysfibrinogenemia associated with hepatoma. Increased carbohydrate content of the fibrinogen molecule. Abnormal coagulation studies indicative of a dysfibrinogen were found in the plasma of four of seven patients with malignant hepatoma. The abnormal fibrinogen was characterized by prolonged prothrombin, thrombin and reptilase times and inhibition of the coagulation of normal plasma. Purified fibrinogen revealed abnormalities similar to those in plasma. The functional defect was one of delayed polymerization of the fibrin monomer. The carbohydrate content of the abnormal fibrinogen was increased, and this change was related to the abnormal fibrinogen function. Enzymatic cleavage of sialic acid from the abnormal fibrinogen restored fibrinogen function to normal. This hepatoma-associated dysfibrinogen (acquired dysfibrinogenemia) is similar in many respects to fetal fibrinogen and may represent the presence of a fetal form of fibrinogen in hepatoma."}
{"id": "PMID:208002", "title": "Alterations in the surface properties of cells responsive to nerve growth factor.", "content": "An initial effect of nerve growth factor on a responsive nerve cell line is to increase intracellular cyclic AMP, which in turn leads to a mobilisation of calcium ions. These events are correlated with structural changes in the plasma membrane, increased cell-substratum adhesion, and neurite outgrowth.", "contents": "Alterations in the surface properties of cells responsive to nerve growth factor. An initial effect of nerve growth factor on a responsive nerve cell line is to increase intracellular cyclic AMP, which in turn leads to a mobilisation of calcium ions. These events are correlated with structural changes in the plasma membrane, increased cell-substratum adhesion, and neurite outgrowth."}
{"id": "PMID:208009", "title": "Diethylstilbestrol potentiation of the dopamine-elicited formation of adenosine 3',5'-monophosphate in incubated male rat hypothalamus.", "content": "Dopamine (DA) stimulates the cAMP-generating system in the male rat hypothalamus only to a very low extent (25% above control). Diethylstilbestrol (DES), a synthetic estrogen, was found to be extremely potent (a 4- and 16-fold stimulation at 20 micron and 100 micron, respectively). Addition of either one to an incubation medium containing varying concentrations of the other resulted in a synergistic response. The potentiation by 20 micron DES of the effect elicited by 100 micron DA was the most remarkable, namely, a 3-fold stimulation of the combined response. A 4- and 7.5-fold stimulation of cAMP accumulation was observed when adenosine (100 micron) or adenosine (100 micron) + DA (100 micron) were present in the incubation medium. Theophylline (0.5 mM), an adenosine antagonist, could effectively reduce this effect, as did adenosine deaminase (10 microgram/ml). Clomiphene (50 micron), an estrogen antagonist, exhibited a marked decrease in DES + DA-elicited cAMP formation. Pimozide (40 micron) had the ability to significantly block the stimulatory effects of DES and DA.", "contents": "Diethylstilbestrol potentiation of the dopamine-elicited formation of adenosine 3',5'-monophosphate in incubated male rat hypothalamus. Dopamine (DA) stimulates the cAMP-generating system in the male rat hypothalamus only to a very low extent (25% above control). Diethylstilbestrol (DES), a synthetic estrogen, was found to be extremely potent (a 4- and 16-fold stimulation at 20 micron and 100 micron, respectively). Addition of either one to an incubation medium containing varying concentrations of the other resulted in a synergistic response. The potentiation by 20 micron DES of the effect elicited by 100 micron DA was the most remarkable, namely, a 3-fold stimulation of the combined response. A 4- and 7.5-fold stimulation of cAMP accumulation was observed when adenosine (100 micron) or adenosine (100 micron) + DA (100 micron) were present in the incubation medium. Theophylline (0.5 mM), an adenosine antagonist, could effectively reduce this effect, as did adenosine deaminase (10 microgram/ml). Clomiphene (50 micron), an estrogen antagonist, exhibited a marked decrease in DES + DA-elicited cAMP formation. Pimozide (40 micron) had the ability to significantly block the stimulatory effects of DES and DA."}
{"id": "PMID:208010", "title": "Demonstration in human atrial preparations of alpha-adrenoceptors mediating positive inotropic effects.", "content": "In isolated, electrically driven right auricular strips of the human heart the inotropic effect of phenylephrine was studied. 1. First, the influence of the driving rate on the tension developed (i.e., the frequency-force relationship) was determined by stimulation of the preparations at 0.1, 0.5, 1, 2 and 3 HZ. The force of contraction was lowest at a stimulation rate of 0.1 HZ (36.9 g/g dry weight). The maximally developed force of contraction observed at frequencies of 0.5, 1 and 2 HZ amounted to about 200 g/g dry weight. The values did not significantly differ from each other. 2. The negative log of the EC50 (-log EC50) for the positive inotropic effect of phenylephrine determined at a frequency of 0.5 and 1.0 HZ amounted to 5.28 +/- 0.08 and 5.34 +/- 0.11, respectively. The alpha-adrenolytic drug phentolamine (3 x 10(-6) M) diminished significantly the -log EC50 to 5.01 +/- 0.04 and 4.89 +/- 0.10, respectively. 3. At a frequency of 1 HZ a shift of the concentration-response curve to the right was observed after treatment with the beta-adrenolytic drug pindolol (3 x 10(-8) M); the -log EC50 of phenylephrine decreased significantly to 4.08 +/- 0.07. 4. From these results it is concluded that alpha-adrenoceptors are present in human atria; they mediate positive inotropic effects and are stimulated by phenylephrine.", "contents": "Demonstration in human atrial preparations of alpha-adrenoceptors mediating positive inotropic effects. In isolated, electrically driven right auricular strips of the human heart the inotropic effect of phenylephrine was studied. 1. First, the influence of the driving rate on the tension developed (i.e., the frequency-force relationship) was determined by stimulation of the preparations at 0.1, 0.5, 1, 2 and 3 HZ. The force of contraction was lowest at a stimulation rate of 0.1 HZ (36.9 g/g dry weight). The maximally developed force of contraction observed at frequencies of 0.5, 1 and 2 HZ amounted to about 200 g/g dry weight. The values did not significantly differ from each other. 2. The negative log of the EC50 (-log EC50) for the positive inotropic effect of phenylephrine determined at a frequency of 0.5 and 1.0 HZ amounted to 5.28 +/- 0.08 and 5.34 +/- 0.11, respectively. The alpha-adrenolytic drug phentolamine (3 x 10(-6) M) diminished significantly the -log EC50 to 5.01 +/- 0.04 and 4.89 +/- 0.10, respectively. 3. At a frequency of 1 HZ a shift of the concentration-response curve to the right was observed after treatment with the beta-adrenolytic drug pindolol (3 x 10(-8) M); the -log EC50 of phenylephrine decreased significantly to 4.08 +/- 0.07. 4. From these results it is concluded that alpha-adrenoceptors are present in human atria; they mediate positive inotropic effects and are stimulated by phenylephrine."}
{"id": "PMID:208011", "title": "Decreased cAMP content of the hypothalamus of genetically hypertensive rats.", "content": "In genetically hypertensive rats an altered catecholamine content of hypothalamic structures has been reported. In the present study cAMP was estimated in the hypothalamus and cortex of genetically hypertensive rats and compared with normotensive controls of the same strain. It is shown, that the cAMP content of the hypothalamus of the hypertensive animals was decreased to about 60% of control values, whereas there was no difference of the cAMP content in the cortical regions of the same animals. These results indicate an alteration of the adenyl cyclase-cAMP-phosphodiesterase system in hypothalamic structures of genetically hypertensive rats.", "contents": "Decreased cAMP content of the hypothalamus of genetically hypertensive rats. In genetically hypertensive rats an altered catecholamine content of hypothalamic structures has been reported. In the present study cAMP was estimated in the hypothalamus and cortex of genetically hypertensive rats and compared with normotensive controls of the same strain. It is shown, that the cAMP content of the hypothalamus of the hypertensive animals was decreased to about 60% of control values, whereas there was no difference of the cAMP content in the cortical regions of the same animals. These results indicate an alteration of the adenyl cyclase-cAMP-phosphodiesterase system in hypothalamic structures of genetically hypertensive rats."}
{"id": "PMID:208014", "title": "Possible role of the proximal convoluted tubules of human kidney in chronic glomerulonephritis. A quantitative electron-microscopic study.", "content": "The amount of forming pinocytic (coated) microvesicles on the apical plasma membrane of kidney proximal tubule cells was assessed in kidney biopsies of 10 patients suffering from chronic glomerulonephritis. A significant correlation was found between the amount of these vesicles and diurnal proteinuria levels (r = 0.889; p less than 0.01). The possible mechanisms of protein reabsorption via pinocytosis in both normal and pathological conditions are considered.", "contents": "Possible role of the proximal convoluted tubules of human kidney in chronic glomerulonephritis. A quantitative electron-microscopic study. The amount of forming pinocytic (coated) microvesicles on the apical plasma membrane of kidney proximal tubule cells was assessed in kidney biopsies of 10 patients suffering from chronic glomerulonephritis. A significant correlation was found between the amount of these vesicles and diurnal proteinuria levels (r = 0.889; p less than 0.01). The possible mechanisms of protein reabsorption via pinocytosis in both normal and pathological conditions are considered."}
{"id": "PMID:208015", "title": "Susceptibility of human embryonic kidneys in organ culture to herpesvirus hominis.", "content": "101 pairs of human embryonic kidneys of 5-12 weeks' gestation were maintained in whole organ culture by our previously described technique, with herpesvirus hominis types1 and 2 added to our regular media. One kidney of each pair served as a control and was exposed to identical culture medium without virus. Cultures were maintained for 24-120 h to study the time sequence of viral infectivity. Organs were then examined for the presence of virus by electron microscopy and histochemical staining. Histological studies of virus-infected kidneys showed either (1) complete organ death or (2) virus localization in undifferentiated cells, plus disorganization of architecture in differentiated areas. Control organs showed normal organization.", "contents": "Susceptibility of human embryonic kidneys in organ culture to herpesvirus hominis. 101 pairs of human embryonic kidneys of 5-12 weeks' gestation were maintained in whole organ culture by our previously described technique, with herpesvirus hominis types1 and 2 added to our regular media. One kidney of each pair served as a control and was exposed to identical culture medium without virus. Cultures were maintained for 24-120 h to study the time sequence of viral infectivity. Organs were then examined for the presence of virus by electron microscopy and histochemical staining. Histological studies of virus-infected kidneys showed either (1) complete organ death or (2) virus localization in undifferentiated cells, plus disorganization of architecture in differentiated areas. Control organs showed normal organization."}
{"id": "PMID:208017", "title": "[Triple contrast ventriculography using air-lipiodol-dimer].", "content": "A mixture of three contrast media - air, Lipiodol and Dimer - was used in ventriculography in order to combine the advantages of each of them. Air is used for topographical localisation, Dimer shows the overall shape of the ventricular system and Lipiodol outlines blocks. This simple and rapid technique provides easily interpretable films, whatever the indication for the ventriculography.", "contents": "[Triple contrast ventriculography using air-lipiodol-dimer]. A mixture of three contrast media - air, Lipiodol and Dimer - was used in ventriculography in order to combine the advantages of each of them. Air is used for topographical localisation, Dimer shows the overall shape of the ventricular system and Lipiodol outlines blocks. This simple and rapid technique provides easily interpretable films, whatever the indication for the ventriculography."}
{"id": "PMID:208021", "title": "[The nature of crystals in plasma cells present in a case of apparently benign biclonal gammapathy].", "content": "A 77 years old white man presents, in his blood serum, a moderate gammapathy with 2 monoclonal peaks, IgAk and IgGlambda, and in his urine a little quantity of BJk, without any clinical or radiological manifestation. The sternal bone marrow showed 3-5% plasmacells, mostly containing many needlelike inclusions in the cytoplasm. These inclusions, red-violet at the May-Gr\u00fcnwald-Giemsa, were PAS and Sudan negative; positive at the Danielli reaction (for proteins). The alpha-naphtil-acetate-esterase and the acid phosphatase were present in one outer layer of the inclusions; ATP-ase was absent. At the electron microscopy, the inclusions were localized outside the rough endoplasmic reticulum; they exhibited a crystalline structure and were surrounded by an envelope which reminded the lysosomes. Basing on the morphological pattern, as well as on the presence of some lysosomal enzymes and on the lack of staining of crystals with fluorescinated anti-Ig sera, the hypothesis is stressed of an abnormal lysosomal hyperactivity, possibly leading to crystallization of the enzymatic proteins in the lysosomes.", "contents": "[The nature of crystals in plasma cells present in a case of apparently benign biclonal gammapathy]. A 77 years old white man presents, in his blood serum, a moderate gammapathy with 2 monoclonal peaks, IgAk and IgGlambda, and in his urine a little quantity of BJk, without any clinical or radiological manifestation. The sternal bone marrow showed 3-5% plasmacells, mostly containing many needlelike inclusions in the cytoplasm. These inclusions, red-violet at the May-Gr\u00fcnwald-Giemsa, were PAS and Sudan negative; positive at the Danielli reaction (for proteins). The alpha-naphtil-acetate-esterase and the acid phosphatase were present in one outer layer of the inclusions; ATP-ase was absent. At the electron microscopy, the inclusions were localized outside the rough endoplasmic reticulum; they exhibited a crystalline structure and were surrounded by an envelope which reminded the lysosomes. Basing on the morphological pattern, as well as on the presence of some lysosomal enzymes and on the lack of staining of crystals with fluorescinated anti-Ig sera, the hypothesis is stressed of an abnormal lysosomal hyperactivity, possibly leading to crystallization of the enzymatic proteins in the lysosomes."}
{"id": "PMID:208023", "title": "[Calcitonin, gastrin, parathyroid hormone and the autonomic nervous system].", "content": "Stimulation of the beta-adrenergic terminations was employed to determine whether calcitonin-secreting thyroid C cells are derived from the neural crest. Calcitonin secretion was increased, whereas parathormone, insulin and gastrin values were not significantly changed. In addition, administration of a beta-blocking drug before ethanol led to a marked fall in calcitonin with respect to the baseline. Once again, other hormone levels were not affected.", "contents": "[Calcitonin, gastrin, parathyroid hormone and the autonomic nervous system]. Stimulation of the beta-adrenergic terminations was employed to determine whether calcitonin-secreting thyroid C cells are derived from the neural crest. Calcitonin secretion was increased, whereas parathormone, insulin and gastrin values were not significantly changed. In addition, administration of a beta-blocking drug before ethanol led to a marked fall in calcitonin with respect to the baseline. Once again, other hormone levels were not affected."}
{"id": "PMID:208025", "title": "[Behavior of total lipids, cholesterol, lipoproteins and apolipoprotein A in the blood of subjects with acute hepatitis and chronic hepatopathy].", "content": "Serum total lipids, lipoprotein cholesterol, apolipoprotein A (Apo A) and liver function parameters have been investigated in patients with acute viral hepatitis and chronic liver disease. Hypertriglyceridaemia, absence of alpha and pre beta bands on the lipoprotein electrophoresis pattern, low level of Apo A, presence of abnormal lipoproteins (beta-VLDL and beta2-LP) were observed in the early phase of acute hepatitis. A positive correlation was found between Apo A and triglyceride bile acids, log total bilirubin, log SGPT. Lipoprotein abnormalities are probably due to low lecitin-cholesterol aciltransferasi activity. The reappearance of alpha lipoprotein and the increase of Apo A are sensitive indices of improvement of liver function. In chronic liver disease the levels of cholesterol and Apo A correlate with changes in the hepatocellular function.", "contents": "[Behavior of total lipids, cholesterol, lipoproteins and apolipoprotein A in the blood of subjects with acute hepatitis and chronic hepatopathy]. Serum total lipids, lipoprotein cholesterol, apolipoprotein A (Apo A) and liver function parameters have been investigated in patients with acute viral hepatitis and chronic liver disease. Hypertriglyceridaemia, absence of alpha and pre beta bands on the lipoprotein electrophoresis pattern, low level of Apo A, presence of abnormal lipoproteins (beta-VLDL and beta2-LP) were observed in the early phase of acute hepatitis. A positive correlation was found between Apo A and triglyceride bile acids, log total bilirubin, log SGPT. Lipoprotein abnormalities are probably due to low lecitin-cholesterol aciltransferasi activity. The reappearance of alpha lipoprotein and the increase of Apo A are sensitive indices of improvement of liver function. In chronic liver disease the levels of cholesterol and Apo A correlate with changes in the hepatocellular function."}
{"id": "PMID:208034", "title": "Replacement estrogen therapy for menopausal vasomotor flushes. Comparison of quinestrol and conjugated estrogens.", "content": "Quinestrol, conjugated estrogens, or placebo was used to treat 156 patients with pernicious vasomotor instability in a prospective, double-blind, randomized, multiinvestigator trial. Vasomotor flushes were severe in approximately 80% of the cases and moderate in 20%, relatively equally distributed among the various drug groups. Both qinestrol and conjugated estrogens were significantly more effective than placebo in relieving vasomotor symptoms (by chi2 analysis, P less than or equal to 0.05). Greatest improvement was seen in the group receiving the higher once weekly quinestrol dosage of 0.2 mg followed by the group on the lower quinestrol dosage of 0.1 mg once weekly and the group on conjugated estrogens, 1.25 mg daily for 21 days on and 7 days off. No significant difference in relief of vasomotor flushes was shown between the active drug groups. No drug-related complications or side reactions of significance occurred. The results indicate that once weekly quinestrol is effective in relieving the vasomotor symptoms of the menopause. Either of two once weekly quinestrol regimens is an effective as conjugated estrogens given daily in a cyclic manner and therefore offers an alternative form of exogenous estrogen therapy.", "contents": "Replacement estrogen therapy for menopausal vasomotor flushes. Comparison of quinestrol and conjugated estrogens. Quinestrol, conjugated estrogens, or placebo was used to treat 156 patients with pernicious vasomotor instability in a prospective, double-blind, randomized, multiinvestigator trial. Vasomotor flushes were severe in approximately 80% of the cases and moderate in 20%, relatively equally distributed among the various drug groups. Both qinestrol and conjugated estrogens were significantly more effective than placebo in relieving vasomotor symptoms (by chi2 analysis, P less than or equal to 0.05). Greatest improvement was seen in the group receiving the higher once weekly quinestrol dosage of 0.2 mg followed by the group on the lower quinestrol dosage of 0.1 mg once weekly and the group on conjugated estrogens, 1.25 mg daily for 21 days on and 7 days off. No significant difference in relief of vasomotor flushes was shown between the active drug groups. No drug-related complications or side reactions of significance occurred. The results indicate that once weekly quinestrol is effective in relieving the vasomotor symptoms of the menopause. Either of two once weekly quinestrol regimens is an effective as conjugated estrogens given daily in a cyclic manner and therefore offers an alternative form of exogenous estrogen therapy."}
{"id": "PMID:208035", "title": "Relation of herpesvirus hominis type II to carcinoma of the cervix. An animal model for the induction of long-term latency of herpesvirus hominis type II.", "content": "Proof of latency of herpesvirus hominis type II (HVH-II) following acute vaginocervical infection must be validated if it is to be considered an etiologic factor in carcinoma of the cervix. An animal model is presented which demonstrates acute HVH-II vaginocervical infection. Following the primary acute infection, animals maintained for an equivalent of 60 human years display persistance of the herpesvirus in the pelvic sensory ganglia. Evidence of the specificity of HVH-II as the infectious agent is presented.", "contents": "Relation of herpesvirus hominis type II to carcinoma of the cervix. An animal model for the induction of long-term latency of herpesvirus hominis type II. Proof of latency of herpesvirus hominis type II (HVH-II) following acute vaginocervical infection must be validated if it is to be considered an etiologic factor in carcinoma of the cervix. An animal model is presented which demonstrates acute HVH-II vaginocervical infection. Following the primary acute infection, animals maintained for an equivalent of 60 human years display persistance of the herpesvirus in the pelvic sensory ganglia. Evidence of the specificity of HVH-II as the infectious agent is presented."}
{"id": "PMID:208037", "title": "Sheep erythrocyte and bluetongue virus antibody responses of spleen cell cultures from mice.", "content": "The optimum conditions for the culture of cells from dissociated spleens were determined. Routinely, 10(7) cells were seeded per ml of RPMI 1640 medium supplemented with 20% pre-tested foetal calf serum. For the assay of the immune response, cultures were supplemented with 30 muMolar mercaptoethanol. The immune responses to sheep erythrocyte and bluetongue virus antigens were determined by the haemolytic plaque-forming cell assays described by Oellermann (1974) and Oellermann, Carter & Marx (1976a). The optimum sheep erythrocyte antigen concentration was 2 X 10(6) erythrocytes per 10(7) spleen cells and maximum IgM plaque-forming cells were detected after 4 days in culture. Successful stimulation of the immune response to bluetongue virus was achieved in spleen cell cultures from mice previously primed with bluetongue virus. The optimum antigen concentration was 30-40 ng bluetongue virus per 10(7) spleen cells and the maximum plaque-forming cell response was observed after 4 days in culture.", "contents": "Sheep erythrocyte and bluetongue virus antibody responses of spleen cell cultures from mice. The optimum conditions for the culture of cells from dissociated spleens were determined. Routinely, 10(7) cells were seeded per ml of RPMI 1640 medium supplemented with 20% pre-tested foetal calf serum. For the assay of the immune response, cultures were supplemented with 30 muMolar mercaptoethanol. The immune responses to sheep erythrocyte and bluetongue virus antigens were determined by the haemolytic plaque-forming cell assays described by Oellermann (1974) and Oellermann, Carter & Marx (1976a). The optimum sheep erythrocyte antigen concentration was 2 X 10(6) erythrocytes per 10(7) spleen cells and maximum IgM plaque-forming cells were detected after 4 days in culture. Successful stimulation of the immune response to bluetongue virus was achieved in spleen cell cultures from mice previously primed with bluetongue virus. The optimum antigen concentration was 30-40 ng bluetongue virus per 10(7) spleen cells and the maximum plaque-forming cell response was observed after 4 days in culture."}
{"id": "PMID:208043", "title": "Predicting adult stature without skeletal age and without paternal data.", "content": "The RWT method for predicting adult stature from childhood variables uses the current recumbent length and weight of the child, the stature of each parent, and the skeletal age of the child as predictor variables. There is only a small increase in the errors of prediction if population mean values are substituted in the prediction equations when the father's stature, the skeletal age of the child, or both these variables are unknown. This modified method is more generally applicable than the original RWT method.", "contents": "Predicting adult stature without skeletal age and without paternal data. The RWT method for predicting adult stature from childhood variables uses the current recumbent length and weight of the child, the stature of each parent, and the skeletal age of the child as predictor variables. There is only a small increase in the errors of prediction if population mean values are substituted in the prediction equations when the father's stature, the skeletal age of the child, or both these variables are unknown. This modified method is more generally applicable than the original RWT method."}
{"id": "PMID:208044", "title": "Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion.", "content": "The triad of aniridia, ambiguous genitalia, and mental retardation (AGR triad) is the characteristic clinical feature of three unrelated patients with previously unreported chromosome 11 short arm interstitial deletions. A Wilms' tumor in one patient establishes one cause for the aniridia-Wilms' tumor association. The genetic heterogeneity of aniridia, the AGR triad, and Wilms' tumor are demonstrated, and Wilms' tumor is indicated to be a neoplastic birth defect which can result from a variety of embryologic insults, some of which may be chromosomal or heritable.", "contents": "Chromosomal imbalance in the Aniridia-Wilms' tumor association: 11p interstitial deletion. The triad of aniridia, ambiguous genitalia, and mental retardation (AGR triad) is the characteristic clinical feature of three unrelated patients with previously unreported chromosome 11 short arm interstitial deletions. A Wilms' tumor in one patient establishes one cause for the aniridia-Wilms' tumor association. The genetic heterogeneity of aniridia, the AGR triad, and Wilms' tumor are demonstrated, and Wilms' tumor is indicated to be a neoplastic birth defect which can result from a variety of embryologic insults, some of which may be chromosomal or heritable."}
{"id": "PMID:208050", "title": "Field dependence and the effect of REM deprivation on thirst.", "content": "Recently a number of studies have concerned the possible function of rapid eye movement (REM) sleep and the mastery of stress. The present study was designed to explore the possibility that REM sleep might play a function in reducing the potency of a stressful physiological stimulus, thirst, as well as the possibility that such a function might be specific to individuals falling at different points along the field-dependence dimension. While there was no difference between REM deprivation and non-REM awakening nights in subsequent morning thirst, there was a significant interaction between field dependence and night on morning thirst measures for 10 college students. These results are discussed in light of previous work on stylistic differences in dreaming and their possible role in adaptation to stress.", "contents": "Field dependence and the effect of REM deprivation on thirst. Recently a number of studies have concerned the possible function of rapid eye movement (REM) sleep and the mastery of stress. The present study was designed to explore the possibility that REM sleep might play a function in reducing the potency of a stressful physiological stimulus, thirst, as well as the possibility that such a function might be specific to individuals falling at different points along the field-dependence dimension. While there was no difference between REM deprivation and non-REM awakening nights in subsequent morning thirst, there was a significant interaction between field dependence and night on morning thirst measures for 10 college students. These results are discussed in light of previous work on stylistic differences in dreaming and their possible role in adaptation to stress."}
{"id": "PMID:208057", "title": "[Whited Addison's disease. Eight cases (author's transl)].", "content": "In 8 cases of Addison's disease due to adrenal tuberculosis, the substitutive treatment appeared unnecessary since more than one year. Urinary 17-OHCS were in the normal range but did not rise after ACTH injection except in two cases. In all the cases, plasma ACTH was elevated but lower than in severe adrenal insufficiency, and in the range of those observed in congenital adrenal hyperplasia. The nycthemeral variation of plasma ACTH were maintained. Therefore, an apparently normal basal cortico-adrenal function was obtained by an excessive stimulation by endogenous ACTH. The one year prescription of anti-tuberculosis chimiotherapy to 6 of these patients was possibly responsible for the partial reversal of adrenal insufficiency. However the substutive therapy appears needless in every day life, such a treatment would eventually be necessary during stress conditions.", "contents": "[Whited Addison's disease. Eight cases (author's transl)]. In 8 cases of Addison's disease due to adrenal tuberculosis, the substitutive treatment appeared unnecessary since more than one year. Urinary 17-OHCS were in the normal range but did not rise after ACTH injection except in two cases. In all the cases, plasma ACTH was elevated but lower than in severe adrenal insufficiency, and in the range of those observed in congenital adrenal hyperplasia. The nycthemeral variation of plasma ACTH were maintained. Therefore, an apparently normal basal cortico-adrenal function was obtained by an excessive stimulation by endogenous ACTH. The one year prescription of anti-tuberculosis chimiotherapy to 6 of these patients was possibly responsible for the partial reversal of adrenal insufficiency. However the substutive therapy appears needless in every day life, such a treatment would eventually be necessary during stress conditions."}
{"id": "PMID:208054", "title": "Testing blood plasma from cattle in leukosos-free herds for antibodies against bovine leukemia virus (BLV).", "content": "As a prelude to the introduction of serological methods in the Danish leukosis eradication programme, an examination for antibody to Bovine Leukemia Virus (BLV) was carried out in 215 randomly selected leukosis-free herds in three areas where 3 routine haematological screening tests had bee made over a period of 6 years. A gel diffusion test was applied to plasma samples. Of 3319 animals screened, none were found to have detectable levels of antibody to BLV in their plasma. This would seem to indicate that false positive reactions are not a serious problem in connection with this test, and also that herds classified as leukosis-free after a series of haematological herd tests carried out within a period of some years, are in fact free from infection with Bovine Leukemia Virus.", "contents": "Testing blood plasma from cattle in leukosos-free herds for antibodies against bovine leukemia virus (BLV). As a prelude to the introduction of serological methods in the Danish leukosis eradication programme, an examination for antibody to Bovine Leukemia Virus (BLV) was carried out in 215 randomly selected leukosis-free herds in three areas where 3 routine haematological screening tests had bee made over a period of 6 years. A gel diffusion test was applied to plasma samples. Of 3319 animals screened, none were found to have detectable levels of antibody to BLV in their plasma. This would seem to indicate that false positive reactions are not a serious problem in connection with this test, and also that herds classified as leukosis-free after a series of haematological herd tests carried out within a period of some years, are in fact free from infection with Bovine Leukemia Virus."}
{"id": "PMID:208053", "title": "Persistence of infection with infectious bovine rhinotracheitis virus in Danish cattle herds.", "content": "The later course of IBR virus infections in 11 dairy herds in endemic areas and in an imported beef herd is described. In 2 herds the infection was limited to those animals which developed a genital infection after insemination with semen from an infected AI centre. In two other herds where genital infection was observed clinically a spreading occurred, probably because of carelessness in clinical examinations, although the possibility of an additional spreading by the respiratory route had to be considered, too. In one herd signs of a respiratory disorder were noticed and assumed to have been caused directly by IBR virus. In the other 7 herds a spreading by the respiratory route was evidenced serologically. In some of these herds there were no indications of spreading after the extensive initial spreading, while in others there were single cases of infection later on, in particular in one small herd where the ventilation was inadequate.", "contents": "Persistence of infection with infectious bovine rhinotracheitis virus in Danish cattle herds. The later course of IBR virus infections in 11 dairy herds in endemic areas and in an imported beef herd is described. In 2 herds the infection was limited to those animals which developed a genital infection after insemination with semen from an infected AI centre. In two other herds where genital infection was observed clinically a spreading occurred, probably because of carelessness in clinical examinations, although the possibility of an additional spreading by the respiratory route had to be considered, too. In one herd signs of a respiratory disorder were noticed and assumed to have been caused directly by IBR virus. In the other 7 herds a spreading by the respiratory route was evidenced serologically. In some of these herds there were no indications of spreading after the extensive initial spreading, while in others there were single cases of infection later on, in particular in one small herd where the ventilation was inadequate."}
{"id": "PMID:208059", "title": "RNA:DNA hybrids are more stable than DNA:DNA duplexes in concentrated perchlorate and trichloroacetate solutions.", "content": "Rates of formation of RNA:DNA hybrids have been measured as a function of temperature and compared to DNA:RNA duplex denaturation temperatures in 4 M sodium perchlorate, 4 M NaClO4-6 M urea, and 3 M rubidium trichloracetate solvents. The usual bell shaped curves of reaction rate versus temperature were observed. The optimal temperatures for the RNA:DNA association reaction are 5 degrees to 12 degrees greater than the Tm's for DNA:DNA denaturation in these solvents, just as in formamide. R-loops of phi80d3ilv DNA with E. coli rRNA can be formed at high efficiency in these solvents.", "contents": "RNA:DNA hybrids are more stable than DNA:DNA duplexes in concentrated perchlorate and trichloroacetate solutions. Rates of formation of RNA:DNA hybrids have been measured as a function of temperature and compared to DNA:RNA duplex denaturation temperatures in 4 M sodium perchlorate, 4 M NaClO4-6 M urea, and 3 M rubidium trichloracetate solvents. The usual bell shaped curves of reaction rate versus temperature were observed. The optimal temperatures for the RNA:DNA association reaction are 5 degrees to 12 degrees greater than the Tm's for DNA:DNA denaturation in these solvents, just as in formamide. R-loops of phi80d3ilv DNA with E. coli rRNA can be formed at high efficiency in these solvents."}
{"id": "PMID:208060", "title": "DNA polymerase alpha is associated with replicating SV40 nucleoprotein complexes.", "content": "Simian virus 40 (SV40) nucleoprotein complexes were extracted from nuclei of infected monkey cells and fractionated on neutral sucrose density gradients. Complexes which contained replicating SV40 DNA (95S) separated well from those containing closed circular supercoiled viral DNA (75S). DNA polymerase activity was associated with the replicating nucleoprotein complexes but not with the slower sedimenting complexes. This DNA polymerase activity coprecipitated with the nucleoprotein complexes in the presence of MgCl2 and remained associated with the 95S complexes. This DNA polymerase activity has been identified as primarily DNA polymerase alpha on the basis of its sedimentation behavior, optimum salt concentration, and sensitivity to N-ethylmaleimide. DNA polymerase gamma activity was also detected in the complexes, but DNA polymerase beta was not associated with the complexes.", "contents": "DNA polymerase alpha is associated with replicating SV40 nucleoprotein complexes. Simian virus 40 (SV40) nucleoprotein complexes were extracted from nuclei of infected monkey cells and fractionated on neutral sucrose density gradients. Complexes which contained replicating SV40 DNA (95S) separated well from those containing closed circular supercoiled viral DNA (75S). DNA polymerase activity was associated with the replicating nucleoprotein complexes but not with the slower sedimenting complexes. This DNA polymerase activity coprecipitated with the nucleoprotein complexes in the presence of MgCl2 and remained associated with the 95S complexes. This DNA polymerase activity has been identified as primarily DNA polymerase alpha on the basis of its sedimentation behavior, optimum salt concentration, and sensitivity to N-ethylmaleimide. DNA polymerase gamma activity was also detected in the complexes, but DNA polymerase beta was not associated with the complexes."}
{"id": "PMID:208065", "title": "[Distribution of Cl. perfringens in preserved food and the lecithinase activity of isolated strains].", "content": "This is a study of 414 different foodstuff types for Cl. perfringens presence determination. Of the meat products are with the highest contamination - 32 per cent, next ranking seasoning spices ond condiments, and auxiliary materials - 10.9 per cent. In milk, dairy and confectionary products it is isolated in 3.8 per cent of samples, while in tinned foodstuffs - in 1.8 per cent. Lecithinase production of the isolated strains in Kitt-Tarozi bouillon, Following 18-20 hour-long cultivation at 37 degrees C is studied, and dosed within limits ranging from 5 to 100 DMO. In meat food - pork in its own sauce, the development and lecithinase activity of some strains with different doses lecithinase in the enriching bouillon is studied after cultivation of the same at room temperature for 18-20 hours. Under the conditions outlined it is established that the growth of the strains is analogical to that of the bouillon, whilst their lecithinase activity shows a several-fold increase, and is dependent on the individual characteristics of the strains, and on their adaptive properties. The produced quantity of lecithinase does not affect the toxicity of strains upon oral infection of the animals experimented.", "contents": "[Distribution of Cl. perfringens in preserved food and the lecithinase activity of isolated strains]. This is a study of 414 different foodstuff types for Cl. perfringens presence determination. Of the meat products are with the highest contamination - 32 per cent, next ranking seasoning spices ond condiments, and auxiliary materials - 10.9 per cent. In milk, dairy and confectionary products it is isolated in 3.8 per cent of samples, while in tinned foodstuffs - in 1.8 per cent. Lecithinase production of the isolated strains in Kitt-Tarozi bouillon, Following 18-20 hour-long cultivation at 37 degrees C is studied, and dosed within limits ranging from 5 to 100 DMO. In meat food - pork in its own sauce, the development and lecithinase activity of some strains with different doses lecithinase in the enriching bouillon is studied after cultivation of the same at room temperature for 18-20 hours. Under the conditions outlined it is established that the growth of the strains is analogical to that of the bouillon, whilst their lecithinase activity shows a several-fold increase, and is dependent on the individual characteristics of the strains, and on their adaptive properties. The produced quantity of lecithinase does not affect the toxicity of strains upon oral infection of the animals experimented."}
{"id": "PMID:208066", "title": "[Methods of taking alcohol samples on solid adsorbents].", "content": "The effect of silicagel porosity on the adsorptional and desorptional qualities of alcohol is investigated in the course of detecting alcohols in the working environment air. Large porous silicagels, inured at 600 degrees, yield optimal 95 per cent desorption water at sample stay exeeding 2 hrs. A method of taking alcohol samples from the air of the working environment, using 10 cm glass tube filled with two layers silicagel, is developed and introduced in practice.", "contents": "[Methods of taking alcohol samples on solid adsorbents]. The effect of silicagel porosity on the adsorptional and desorptional qualities of alcohol is investigated in the course of detecting alcohols in the working environment air. Large porous silicagels, inured at 600 degrees, yield optimal 95 per cent desorption water at sample stay exeeding 2 hrs. A method of taking alcohol samples from the air of the working environment, using 10 cm glass tube filled with two layers silicagel, is developed and introduced in practice."}
{"id": "PMID:208067", "title": "[Surgical treatment of Wilm's tumours in children (author's transl)].", "content": "Introductory data on nephroblastoma occurence in children is followed by a general discussion on the methods of procedure used in treatment of these tumours in the last century. Then the author gives definite indices how to treat the disease surgically. In the description all groups of clinical advancement (promotion) of the neoplasm and the age of children are mentioned. The paper is supplemented by 20 Polish as well as foreign works (bibliographies).", "contents": "[Surgical treatment of Wilm's tumours in children (author's transl)]. Introductory data on nephroblastoma occurence in children is followed by a general discussion on the methods of procedure used in treatment of these tumours in the last century. Then the author gives definite indices how to treat the disease surgically. In the description all groups of clinical advancement (promotion) of the neoplasm and the age of children are mentioned. The paper is supplemented by 20 Polish as well as foreign works (bibliographies)."}
{"id": "PMID:208064", "title": "[1 alpha-hydroxyvitamin D3: chemical synthesis and biological effect].", "content": "A method for the synthesis of an analog of vitamin D3--1alpha-hydroxy vitamin D3 (1alpha-OH D3) from cholesta-4,6-dien-3beta-ol was developed. Biological activity of this compound in the chick organism was measured. The growth stimulating effect of 1alpha-OH D3 and its effect on bone tissue mineralization and serum biochemical parameters (content of calcium, inorganic phosphorus and activity of alkaline phosphatase) were 4--5 times higher than those of vitamin D3 in low doses (19.5--39 pmole/day). In chicks given 1alpha-OH D3 at doses of 39--195 pmole/day most biochemical parameters reached plateau typical of chicks adequately provided with vitamin D. A peculiar feature of 1alpha-OH D3 was a rapid response of the chick organism to/low doses.  As early as one hour after intramuscular injection of 650 pmole of 1alpha-OH D3 to D-avitaminotic chicks, the content of calcium-bound protein in the intestinal mucosa and active transport of calcium ions in the inverted intestinal sac increased drastically. It was demonstrated that 1alpha-OH D3 showed antirachitic action, when the physiological reaction to vitamin D3 was inhibited by dietary strontium.", "contents": "[1 alpha-hydroxyvitamin D3: chemical synthesis and biological effect]. A method for the synthesis of an analog of vitamin D3--1alpha-hydroxy vitamin D3 (1alpha-OH D3) from cholesta-4,6-dien-3beta-ol was developed. Biological activity of this compound in the chick organism was measured. The growth stimulating effect of 1alpha-OH D3 and its effect on bone tissue mineralization and serum biochemical parameters (content of calcium, inorganic phosphorus and activity of alkaline phosphatase) were 4--5 times higher than those of vitamin D3 in low doses (19.5--39 pmole/day). In chicks given 1alpha-OH D3 at doses of 39--195 pmole/day most biochemical parameters reached plateau typical of chicks adequately provided with vitamin D. A peculiar feature of 1alpha-OH D3 was a rapid response of the chick organism to/low doses.  As early as one hour after intramuscular injection of 650 pmole of 1alpha-OH D3 to D-avitaminotic chicks, the content of calcium-bound protein in the intestinal mucosa and active transport of calcium ions in the inverted intestinal sac increased drastically. It was demonstrated that 1alpha-OH D3 showed antirachitic action, when the physiological reaction to vitamin D3 was inhibited by dietary strontium."}
{"id": "PMID:208068", "title": "Conformationally restricted bicyclic analogs of somatostatin.", "content": "A model for a biologically active conformation of somatostatin is proposed. This model is based primarily on the biological results obtained with novel bicyclic somatostatin analogs having a covalent bridge replacing the side chains of residues 5 and 10, 6 and 11, and 5 and 12, respectively, rather than on physical measurements on the hormone in solution. The high activity of an analog in which Phe6 and Phe11 are replaced by cystine provides evidence that these phenylalanines stabilize the biologically active conformer through \"hydrophobic bonding\" but do not directly interact with the receptor. The synthesis of the novel bicyclic analogs of somatostatin and the effects of these on the inhibition of secretion of insulin, glucagon, growth hormone, and gastric acid are described.", "contents": "Conformationally restricted bicyclic analogs of somatostatin. A model for a biologically active conformation of somatostatin is proposed. This model is based primarily on the biological results obtained with novel bicyclic somatostatin analogs having a covalent bridge replacing the side chains of residues 5 and 10, 6 and 11, and 5 and 12, respectively, rather than on physical measurements on the hormone in solution. The high activity of an analog in which Phe6 and Phe11 are replaced by cystine provides evidence that these phenylalanines stabilize the biologically active conformer through \"hydrophobic bonding\" but do not directly interact with the receptor. The synthesis of the novel bicyclic analogs of somatostatin and the effects of these on the inhibition of secretion of insulin, glucagon, growth hormone, and gastric acid are described."}
{"id": "PMID:208069", "title": "Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system.", "content": "Treatment of pigeon erythrocyte membranes with cholera toxin and NAD(+) enhanced the GTP stimulation and suppressed the F(-) activation of the adenylate cylase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. In the presence of NAD(+) labeled with (32)P in the AMP moiety the toxin catalyzed the covalent incorporation of radioactivity into membrane proteins with molecular weights (M(r)s) of 200,000, 86,000, and 42,000. Extraction of toxin-treated membranes with Lubrol PX followed by affinity chromatography on a GTP-Sepharose column resulted in a 200-fold purification of the 42,000-M(r) labeled protein and in its complete separation from the other labeled proteins. The fraction containing the purified GTP-binding component from toxin-treated membranes conferred an enhanced GTP-stimulated activity on adenylate cyclase solubilized from nontreated membranes. Likewise, the addition of GTP-binding fraction from nontreated membranes to an enzyme solubilized from toxin-treated membranes restored F(-) stimulation of the adenylate cyclase. The toxin-induced modification of adenylate cyclase and the incorporation of radioactivity into the 42,000-M(r) protein were partially reversed upon incubation with toxin and nicotinamide at pH 6.1. The results indicate that cholera toxin affects the adenylate cyclase system by catalyzing an ADP-ribosylation of the 42,000-M(r) component bearing the guanyl nucleotide regulatory site.", "contents": "Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Treatment of pigeon erythrocyte membranes with cholera toxin and NAD(+) enhanced the GTP stimulation and suppressed the F(-) activation of the adenylate cylase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. In the presence of NAD(+) labeled with (32)P in the AMP moiety the toxin catalyzed the covalent incorporation of radioactivity into membrane proteins with molecular weights (M(r)s) of 200,000, 86,000, and 42,000. Extraction of toxin-treated membranes with Lubrol PX followed by affinity chromatography on a GTP-Sepharose column resulted in a 200-fold purification of the 42,000-M(r) labeled protein and in its complete separation from the other labeled proteins. The fraction containing the purified GTP-binding component from toxin-treated membranes conferred an enhanced GTP-stimulated activity on adenylate cyclase solubilized from nontreated membranes. Likewise, the addition of GTP-binding fraction from nontreated membranes to an enzyme solubilized from toxin-treated membranes restored F(-) stimulation of the adenylate cyclase. The toxin-induced modification of adenylate cyclase and the incorporation of radioactivity into the 42,000-M(r) protein were partially reversed upon incubation with toxin and nicotinamide at pH 6.1. The results indicate that cholera toxin affects the adenylate cyclase system by catalyzing an ADP-ribosylation of the 42,000-M(r) component bearing the guanyl nucleotide regulatory site."}
{"id": "PMID:208070", "title": "Epinephrine-induced elevation of guanosine 3':5'-cyclic monophosphate in isolated fat cells of rat.", "content": "The effects of epinephrine (as low as 0.1 muM) on guanosine 3':5'-cyclic monophosphate (cGMP) and adenosine 3':5'-cyclic monophosphate (cAMP) in isolated fat cells were examined. Epinephrine increased both cGMP and cAMP levels, with the elevation of cAMP preceding the rise of cGMP. Maximal elevation was obtained with 1 muM epinephrine for each nucleotide. The increase in content of cGMP and cAMP due to epinephrine was completely blocked by a beta-adrenergic antagonist (5 muM propranolol). Phentolamine (10-100 muM), an alpha-adrenergic antagonist, enhanced the response to epinephrine resulting in elevation of cAMP levels, whereas a high concentration (100 muM) of phentolamine suppressed the elevation of cGMP. The ability of epinephrine to increase cGMP and cAMP levels was markedly diminished by \"feedback regulator\" partially purified from the incubation mixtures of isolated fat cells exposed to epinephrine [Ho, R.J. & Sutherland, E. W. (1971) J. Biol. Chem. 246, 6822-6827], whereas an increase in cGMP, but not cAMP, levels was observed in isolated fat cells incubated with \"feedback regulator\" alone (without epinephrine). These observations suggest the possibility that the epinephrine-induced elevation of cGMP levels in isolated fat cells might be mediated by an increase in formation of intracellular \"feedback regulator\" due to an elevation of cAMP by epinephrine.", "contents": "Epinephrine-induced elevation of guanosine 3':5'-cyclic monophosphate in isolated fat cells of rat. The effects of epinephrine (as low as 0.1 muM) on guanosine 3':5'-cyclic monophosphate (cGMP) and adenosine 3':5'-cyclic monophosphate (cAMP) in isolated fat cells were examined. Epinephrine increased both cGMP and cAMP levels, with the elevation of cAMP preceding the rise of cGMP. Maximal elevation was obtained with 1 muM epinephrine for each nucleotide. The increase in content of cGMP and cAMP due to epinephrine was completely blocked by a beta-adrenergic antagonist (5 muM propranolol). Phentolamine (10-100 muM), an alpha-adrenergic antagonist, enhanced the response to epinephrine resulting in elevation of cAMP levels, whereas a high concentration (100 muM) of phentolamine suppressed the elevation of cGMP. The ability of epinephrine to increase cGMP and cAMP levels was markedly diminished by \"feedback regulator\" partially purified from the incubation mixtures of isolated fat cells exposed to epinephrine [Ho, R.J. & Sutherland, E. W. (1971) J. Biol. Chem. 246, 6822-6827], whereas an increase in cGMP, but not cAMP, levels was observed in isolated fat cells incubated with \"feedback regulator\" alone (without epinephrine). These observations suggest the possibility that the epinephrine-induced elevation of cGMP levels in isolated fat cells might be mediated by an increase in formation of intracellular \"feedback regulator\" due to an elevation of cAMP by epinephrine."}
{"id": "PMID:208071", "title": "The \"sarcoma-specific\" region of Moloney murine sarcoma virus 124.", "content": "Labeled, purified 30S RNA from Moloney murine sarcoma virus was annealed to an excess of Moloney murine leukemia virus complementary DNA. Upon treatment of the resulting DNA.RNA hybrids with RNase H followed by sucrose gradient sedimentation, and undigested 18S RNA molecule was recovered. This RNA molecule was shown to represent the \"sarcoma-specific\" region of the virus. The unintegrated linear DNA provirus of murine sarcoma virus 124 was isolated from newly infected cells and a physical map of the sarcoma-specific region was obtained. First, unintegrated full-length linear proviral DNA molecules were cleaved by several restriction endonucleases. The reciprocal position and orientation with respect to the viral RNA of the resulting fragments were established. The location of the sarcoma-specific region was determined by competition-hybridization with 125I-labeled viral genomic RNAs and proviral DNA fragments. A 1500-base-pair fragment was obtained by cleavage with HindIII + Bgl II. This fragment mapped between 750 and 2250 base pairs from the right end of the proviral DNA (corresponding th the 3' terminus of the viral RNA) and contained the whole set of the sarcoma-specific information. This murine sarcoma virus proviral restriction fragment is approximately of the same size and map position as the isolated 18S sarcoma-specific RNA.", "contents": "The \"sarcoma-specific\" region of Moloney murine sarcoma virus 124. Labeled, purified 30S RNA from Moloney murine sarcoma virus was annealed to an excess of Moloney murine leukemia virus complementary DNA. Upon treatment of the resulting DNA.RNA hybrids with RNase H followed by sucrose gradient sedimentation, and undigested 18S RNA molecule was recovered. This RNA molecule was shown to represent the \"sarcoma-specific\" region of the virus. The unintegrated linear DNA provirus of murine sarcoma virus 124 was isolated from newly infected cells and a physical map of the sarcoma-specific region was obtained. First, unintegrated full-length linear proviral DNA molecules were cleaved by several restriction endonucleases. The reciprocal position and orientation with respect to the viral RNA of the resulting fragments were established. The location of the sarcoma-specific region was determined by competition-hybridization with 125I-labeled viral genomic RNAs and proviral DNA fragments. A 1500-base-pair fragment was obtained by cleavage with HindIII + Bgl II. This fragment mapped between 750 and 2250 base pairs from the right end of the proviral DNA (corresponding th the 3' terminus of the viral RNA) and contained the whole set of the sarcoma-specific information. This murine sarcoma virus proviral restriction fragment is approximately of the same size and map position as the isolated 18S sarcoma-specific RNA."}
{"id": "PMID:208072", "title": "Amino-terminal amino acid sequence of the major structural polypeptides of avian retroviruses: sequence homology between reticuloendotheliosis virus p30 and p30s of mammalian retroviruses.", "content": "The major structural polypeptides, p30 of reticuloendotheliosis virus (REV) (strain T) and p27 of avian sarcoma virus B77, have been compared with regard to amino acid composition. NH2-terminal amino acid sequence, and immunological crossreactions. The amino acid composition of the two polypeptides is distinct, and a comparison of the first 30 NH2-terminal amino acids of REV p30 with that for the first 25 of B77 p27 yields only three homologous residues. In competition radioimmunoassays the polypeptides show no crossreactivity. A comparison of the amino acid composition and NH2-terminal amino acid sequence of REV p30 with those reported for several mammalian retrovirus p30s shows remarkable similarities. Both REV and mammalian p30s contain a large number of polar residues in their amino acid composition and show approximately 40% homology in the first 30 NH2-terminal amino acids. No crossreactivity could be observed, however, in competition radioimmunoassays between Rauscher murine leukemia virus p30 and that of REV. The observations reported here suggest a close evolutionary relationship between REV and the mammalian retroviruses.", "contents": "Amino-terminal amino acid sequence of the major structural polypeptides of avian retroviruses: sequence homology between reticuloendotheliosis virus p30 and p30s of mammalian retroviruses. The major structural polypeptides, p30 of reticuloendotheliosis virus (REV) (strain T) and p27 of avian sarcoma virus B77, have been compared with regard to amino acid composition. NH2-terminal amino acid sequence, and immunological crossreactions. The amino acid composition of the two polypeptides is distinct, and a comparison of the first 30 NH2-terminal amino acids of REV p30 with that for the first 25 of B77 p27 yields only three homologous residues. In competition radioimmunoassays the polypeptides show no crossreactivity. A comparison of the amino acid composition and NH2-terminal amino acid sequence of REV p30 with those reported for several mammalian retrovirus p30s shows remarkable similarities. Both REV and mammalian p30s contain a large number of polar residues in their amino acid composition and show approximately 40% homology in the first 30 NH2-terminal amino acids. No crossreactivity could be observed, however, in competition radioimmunoassays between Rauscher murine leukemia virus p30 and that of REV. The observations reported here suggest a close evolutionary relationship between REV and the mammalian retroviruses."}
{"id": "PMID:208073", "title": "Inhibition of translation by poliovirus: inactivation of a specific initiation factor.", "content": "Translation of vesicular stomatitis virus (VSV) mRNA, like host mRNA translation, is inhibited in cells infected with poliovirus. To study the mechanism of poliovirus-induced inhibition of protein synthesis, we prepared extracts from poliovirus-infected and uninfected HeLa cells. Poliovirus mRNA was translated in lysates from both infected and uninfected cells, while VSV mRNA was translated only in the lysate from uninfected cells. Addition of purified translation initiation factors to the extract from infected cells showed that one factor, eIF-4B, could restore VSV mRNA translation in the infected lysate, but did not increase poliovirus mRNA translation. Further experiments involving translation of VSV mRNA in mixed extracts from poliovirus-infected and uninfected cells showed (i) that there was not an excess of an inhibitor of VSV mRNA translation in the infected lysate, but (ii) that an acitivity that caused a slow inactivation of eIF-4B was present in the infected lysate. Inactivation of eIF-4B appears to be the mechanism by which poliovirus infection causes a selective inhibition of translation.", "contents": "Inhibition of translation by poliovirus: inactivation of a specific initiation factor. Translation of vesicular stomatitis virus (VSV) mRNA, like host mRNA translation, is inhibited in cells infected with poliovirus. To study the mechanism of poliovirus-induced inhibition of protein synthesis, we prepared extracts from poliovirus-infected and uninfected HeLa cells. Poliovirus mRNA was translated in lysates from both infected and uninfected cells, while VSV mRNA was translated only in the lysate from uninfected cells. Addition of purified translation initiation factors to the extract from infected cells showed that one factor, eIF-4B, could restore VSV mRNA translation in the infected lysate, but did not increase poliovirus mRNA translation. Further experiments involving translation of VSV mRNA in mixed extracts from poliovirus-infected and uninfected cells showed (i) that there was not an excess of an inhibitor of VSV mRNA translation in the infected lysate, but (ii) that an acitivity that caused a slow inactivation of eIF-4B was present in the infected lysate. Inactivation of eIF-4B appears to be the mechanism by which poliovirus infection causes a selective inhibition of translation."}
{"id": "PMID:208074", "title": "Purification of the fusion protein of Sendai virus: analysis of the NH2-terminal sequence generated during precursor activation.", "content": "The two glycoproteins of Sendai virus, the hemagglutinin-neuraminidase and the fusion protein (F), were separated and purified by affinity chromatography on a Lens culinaris lectin-Sepharose column. F was shown to consist of two disulfide-bonded glycopolypeptide chains, F1 and F2, of molecular weights 51,000 and 11,000, each of which contained 15% carbohydrate by weight. Amino-terminal sequence analysis showed that F2 was blocked and that the hydrophobic sequence NH2-Phe-Phe-Gly-Ala-Val-Ile-Gly-Ile-Ile-Ala-Leu-Gly-Pro-Ala-Thr- was at the amino terminus of F1. This sequence shows identity at six positions with the hydrophobic amino-terminal sequence of the smaller glycopolypeptide chain, HA2, of the hemagglutinin of influenza virus. Both F1 and HA2 are formed by proteolytic cleavage of precursor glycoproteins (Fo, Sendai virus; HAo, influenza virus). Since these cleavages confer infectivity upon both Sendai and influenza viruses and the ability to induce cell-to-cell fusion upon Sendai virus, the hydrophobic NH2-terminal sequences on F1 and HA2 may play a role in fusion of viral and host-cell membranes.", "contents": "Purification of the fusion protein of Sendai virus: analysis of the NH2-terminal sequence generated during precursor activation. The two glycoproteins of Sendai virus, the hemagglutinin-neuraminidase and the fusion protein (F), were separated and purified by affinity chromatography on a Lens culinaris lectin-Sepharose column. F was shown to consist of two disulfide-bonded glycopolypeptide chains, F1 and F2, of molecular weights 51,000 and 11,000, each of which contained 15% carbohydrate by weight. Amino-terminal sequence analysis showed that F2 was blocked and that the hydrophobic sequence NH2-Phe-Phe-Gly-Ala-Val-Ile-Gly-Ile-Ile-Ala-Leu-Gly-Pro-Ala-Thr- was at the amino terminus of F1. This sequence shows identity at six positions with the hydrophobic amino-terminal sequence of the smaller glycopolypeptide chain, HA2, of the hemagglutinin of influenza virus. Both F1 and HA2 are formed by proteolytic cleavage of precursor glycoproteins (Fo, Sendai virus; HAo, influenza virus). Since these cleavages confer infectivity upon both Sendai and influenza viruses and the ability to induce cell-to-cell fusion upon Sendai virus, the hydrophobic NH2-terminal sequences on F1 and HA2 may play a role in fusion of viral and host-cell membranes."}
{"id": "PMID:208075", "title": "Assay for early cytoplasmic effects of the src gene product of Rous sarcoma virus.", "content": "When microinjected into normal fibroblasts, cytoplasmic extracts of cells transformed by Rous sarcoma virus caused dissolution of microfilament bundles. This activity was not found in extracts of normal cells. The maximum effect was seen within 30 min of injection, and the activity could still be measured after a 10-fold dilution of the cytoplasmic extracts (14 mg/ml original protein concentration). The activity was trypsin sensitive and was destroyed by boiling, but was not RNase sensitive. Protein synthesis was not required for the disruption of actin-containing stress fibers by the injected activity. Microinjected cytoplasts prepared from normal 3T3 cells also showed dissolution of microfilament bundles, indicating that the cell nucleus was not required for expression of activity. Extracts made from fibroblasts transformed by Rous sarcoma virus having a temperature-sensitive mutation in the src gene were also temperature sensitive in the microinjection assay. Thus, the activity of extracts from cells infected with src mutant virus, but not from cells infected with wild-type virus, was destroyed either by in vitro incubation of the extract at the nonpermissive temperature before injection or by incubation of recipient cells at the nonpermissive temperature after injection. We conclude that the microinjection assay can detect a cytoplasmic activity coded for by the src gene of Rous sarcoma virus and that an early direct or indirect target of the src gene product is the cytoskeleton and cell motility system. This result is discussed in relation to the hypothesis that submembranous arrays of microfilaments, microtubules, and their associated proteins interact with cell surface receptors to form a surface modulating assembly that functions as a key regulator of cell growth.", "contents": "Assay for early cytoplasmic effects of the src gene product of Rous sarcoma virus. When microinjected into normal fibroblasts, cytoplasmic extracts of cells transformed by Rous sarcoma virus caused dissolution of microfilament bundles. This activity was not found in extracts of normal cells. The maximum effect was seen within 30 min of injection, and the activity could still be measured after a 10-fold dilution of the cytoplasmic extracts (14 mg/ml original protein concentration). The activity was trypsin sensitive and was destroyed by boiling, but was not RNase sensitive. Protein synthesis was not required for the disruption of actin-containing stress fibers by the injected activity. Microinjected cytoplasts prepared from normal 3T3 cells also showed dissolution of microfilament bundles, indicating that the cell nucleus was not required for expression of activity. Extracts made from fibroblasts transformed by Rous sarcoma virus having a temperature-sensitive mutation in the src gene were also temperature sensitive in the microinjection assay. Thus, the activity of extracts from cells infected with src mutant virus, but not from cells infected with wild-type virus, was destroyed either by in vitro incubation of the extract at the nonpermissive temperature before injection or by incubation of recipient cells at the nonpermissive temperature after injection. We conclude that the microinjection assay can detect a cytoplasmic activity coded for by the src gene of Rous sarcoma virus and that an early direct or indirect target of the src gene product is the cytoskeleton and cell motility system. This result is discussed in relation to the hypothesis that submembranous arrays of microfilaments, microtubules, and their associated proteins interact with cell surface receptors to form a surface modulating assembly that functions as a key regulator of cell growth."}
{"id": "PMID:208076", "title": "Direct evidence for 6-fold symmetry of the herpesvirus hexon capsomere.", "content": "Rotational power spectrum analysis of scanning transmission electron micrographs of negatively stained herpesvirus capsids has given direct evidence for the 6-fold symmetry of the herpesvirus hexon capsomere. Individual hexons have been analyzed in situ without interference from other parts of the capsid because only one level of the capsid was in focus in the micrograph. This study found hexons to have 6-fold symmetry. The majority of the mass of each hexon subunit was seen to lie on a line connecting the centers of adjacent capsomeres. This agrees with analysis of conventional micrographs of capsid fragments, which are also presented, as well as with biochemical data and theoretical expectations.", "contents": "Direct evidence for 6-fold symmetry of the herpesvirus hexon capsomere. Rotational power spectrum analysis of scanning transmission electron micrographs of negatively stained herpesvirus capsids has given direct evidence for the 6-fold symmetry of the herpesvirus hexon capsomere. Individual hexons have been analyzed in situ without interference from other parts of the capsid because only one level of the capsid was in focus in the micrograph. This study found hexons to have 6-fold symmetry. The majority of the mass of each hexon subunit was seen to lie on a line connecting the centers of adjacent capsomeres. This agrees with analysis of conventional micrographs of capsid fragments, which are also presented, as well as with biochemical data and theoretical expectations."}
{"id": "PMID:208077", "title": "Vasoactive intestinal peptide: a potent stimulator of adenosine 3':5'-cyclic monophosphate accumulation in gut carcinoma cell lines in culture.", "content": "Vasoactive intestinal peptide (VIP) is a potent and efficient stimulator of adenosine 3':5'-cyclic monophosphate (cAMP) accumulation in a human colon carcinoma cell line, HT 29. cAMP accumulation is sensitive to a concentration of VIP as low as 3x10(-12) M. Maximum VIP-induced cAMP levels were observed with 10(-9) M VIP and are about 200 times above the basal levels. Half-maximum cAMP production was obtained at 3x10(-10) M VIP. (125)I-Labeled VIP was found to bind to HT 29 cells; this binding was competitively inhibited by concentrations of unlabeled VIP between 10(-10) and 10(-7) M. Half-maximum inhibition of binding was observed with 2x10(-9) M VIP. Secretin also stimulated cAMP accumulation in HT 29 cells, but its effectiveness was 1/1000 that of VIP. The other peptides tested at 10(-7) M, such as insulin, glucagon, bovine pancreatic polypeptide, somatostatin, octapeptide of cholecystokinin, neurotensin, and substance P, did not stimulate cAMP accumulation. Prostaglandin E(1) and catecholamines stimulated cAMP production but were 1/2.3 and 1/5.5 as efficient as VIP, respectively. Another malignant cell line from the gut, the human rectal tumor cell line HRT 18, is also sensitive to VIP. In HRT 18 cells, VIP stimulated cAMP accumulation with a maximal effect at 10(-8) M; half-maximum stimulation was observed at about 10(-9) M. These results demonstrate the presence of VIP receptors in two malignant human intestinal cell lines (HT 29 and HRT 18) in culture and provide a model for studying the action of VIP on cell proliferation.", "contents": "Vasoactive intestinal peptide: a potent stimulator of adenosine 3':5'-cyclic monophosphate accumulation in gut carcinoma cell lines in culture. Vasoactive intestinal peptide (VIP) is a potent and efficient stimulator of adenosine 3':5'-cyclic monophosphate (cAMP) accumulation in a human colon carcinoma cell line, HT 29. cAMP accumulation is sensitive to a concentration of VIP as low as 3x10(-12) M. Maximum VIP-induced cAMP levels were observed with 10(-9) M VIP and are about 200 times above the basal levels. Half-maximum cAMP production was obtained at 3x10(-10) M VIP. (125)I-Labeled VIP was found to bind to HT 29 cells; this binding was competitively inhibited by concentrations of unlabeled VIP between 10(-10) and 10(-7) M. Half-maximum inhibition of binding was observed with 2x10(-9) M VIP. Secretin also stimulated cAMP accumulation in HT 29 cells, but its effectiveness was 1/1000 that of VIP. The other peptides tested at 10(-7) M, such as insulin, glucagon, bovine pancreatic polypeptide, somatostatin, octapeptide of cholecystokinin, neurotensin, and substance P, did not stimulate cAMP accumulation. Prostaglandin E(1) and catecholamines stimulated cAMP production but were 1/2.3 and 1/5.5 as efficient as VIP, respectively. Another malignant cell line from the gut, the human rectal tumor cell line HRT 18, is also sensitive to VIP. In HRT 18 cells, VIP stimulated cAMP accumulation with a maximal effect at 10(-8) M; half-maximum stimulation was observed at about 10(-9) M. These results demonstrate the presence of VIP receptors in two malignant human intestinal cell lines (HT 29 and HRT 18) in culture and provide a model for studying the action of VIP on cell proliferation."}
{"id": "PMID:208078", "title": "beta-Lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant beta-endorphin.", "content": "beta-Lipotropin is the predominant opioid peptide of the human pituitary and rat pars distalis and is present in concentrations essentially equimolar with corticotropin. When freshly, obtained nonfrozen rat anterior pituitaries were homogenized with 0.2 M HCl, approximately 98% of the immunoreactivity detected utilizing an antiserum that crossreacts equally with beta-lipotropin and beta-endorphin coeluted with 125I-labeled human beta-lipotropin upon molecular sieve chromatography. The remainder of the activity eluted with synthetic human beta-endorphin. Similar results were obtained for human pituitary. HCl homogenization of thawed tissue or homogenization of fresh tissue with acetic acid yielded substantially greater concentrations of beta-endorphin and decreased concentrations of beta-lipotropin. In human subjects, acute anterior pituitary stimulation using either insulin-induced hypoglycemia or vasopressin administration was associated with increased plasma beta-lipotropin and corticotropin levels. At the time of peak concentrations, no significant levels of beta-endorphin were detectable. These data indicate the lack of significant amounts of beta-endorphin in human pituitary. Additionally, there appears to be no specific intrapituitary conversion of beta-lipotropin to beta-endorphin.", "contents": "beta-Lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant beta-endorphin. beta-Lipotropin is the predominant opioid peptide of the human pituitary and rat pars distalis and is present in concentrations essentially equimolar with corticotropin. When freshly, obtained nonfrozen rat anterior pituitaries were homogenized with 0.2 M HCl, approximately 98% of the immunoreactivity detected utilizing an antiserum that crossreacts equally with beta-lipotropin and beta-endorphin coeluted with 125I-labeled human beta-lipotropin upon molecular sieve chromatography. The remainder of the activity eluted with synthetic human beta-endorphin. Similar results were obtained for human pituitary. HCl homogenization of thawed tissue or homogenization of fresh tissue with acetic acid yielded substantially greater concentrations of beta-endorphin and decreased concentrations of beta-lipotropin. In human subjects, acute anterior pituitary stimulation using either insulin-induced hypoglycemia or vasopressin administration was associated with increased plasma beta-lipotropin and corticotropin levels. At the time of peak concentrations, no significant levels of beta-endorphin were detectable. These data indicate the lack of significant amounts of beta-endorphin in human pituitary. Additionally, there appears to be no specific intrapituitary conversion of beta-lipotropin to beta-endorphin."}
{"id": "PMID:208079", "title": "Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs.", "content": "Liposomes containing antimonial compounds trapped in the aqueous phase were tested in the treatment of experimental leishmaniasis. The rationale of this approach was based on the hypothesis that the liposomes and the parasite are taken up by the same cell, the reticuloendothelial cell, and we present electron microscopic evidence that supports this hypothesis. Suppression of leishmaniasis was quantified by determining the total number of parasites per liver from impression smears. When two antimonials, meglumine antimoniate and sodium stibogluconate, were encapsulated within liposomes, each was more than 700 times more active compared to either of the free (unencapsulated) drugs. After infection, if untreated, all of the hamsters eventually would die from the disease. Liposome-encapsulated meglumine antimoniate was about 330-640 times more effective in causing a drop in the death rate than was the free antimonial. The efficacy of treatment was influenced by the lipid composition and charge of the liposomes. For example, positively charged liposomes containing egg phosphatidylcholine were much less effective than negatively charged ones. In contrast, positively and negatively charged sphingomyelin liposomes were equally effective. Liposomes containing phosphatidylserine (which were negatively charged, but also had a much higher charge density) were among the less-effective preparations. Among those tested, the most consistently efficacious liposomes contained highly saturated long-chain phospholipids (eg., dipalmitoyl phosphatidylcholine), cholesterol, and a negative charge. We conclude that liposomes may be useful as carriers of drugs to treat infectious diseases involving the reticuloendothelial system. The toxicities of antimony are very similar to those of arsenic. Encapsulation of antimonial drugs and reduction of the dose required for effective therapy should minimize such systemic toxicities as acute cardiomyopathy and toxic nephritis.", "contents": "Therapy of leishmaniasis: superior efficacies of liposome-encapsulated drugs. Liposomes containing antimonial compounds trapped in the aqueous phase were tested in the treatment of experimental leishmaniasis. The rationale of this approach was based on the hypothesis that the liposomes and the parasite are taken up by the same cell, the reticuloendothelial cell, and we present electron microscopic evidence that supports this hypothesis. Suppression of leishmaniasis was quantified by determining the total number of parasites per liver from impression smears. When two antimonials, meglumine antimoniate and sodium stibogluconate, were encapsulated within liposomes, each was more than 700 times more active compared to either of the free (unencapsulated) drugs. After infection, if untreated, all of the hamsters eventually would die from the disease. Liposome-encapsulated meglumine antimoniate was about 330-640 times more effective in causing a drop in the death rate than was the free antimonial. The efficacy of treatment was influenced by the lipid composition and charge of the liposomes. For example, positively charged liposomes containing egg phosphatidylcholine were much less effective than negatively charged ones. In contrast, positively and negatively charged sphingomyelin liposomes were equally effective. Liposomes containing phosphatidylserine (which were negatively charged, but also had a much higher charge density) were among the less-effective preparations. Among those tested, the most consistently efficacious liposomes contained highly saturated long-chain phospholipids (eg., dipalmitoyl phosphatidylcholine), cholesterol, and a negative charge. We conclude that liposomes may be useful as carriers of drugs to treat infectious diseases involving the reticuloendothelial system. The toxicities of antimony are very similar to those of arsenic. Encapsulation of antimonial drugs and reduction of the dose required for effective therapy should minimize such systemic toxicities as acute cardiomyopathy and toxic nephritis."}
{"id": "PMID:208080", "title": "Cell fusion induced by scrapie and Creutzfeldt-Jakob virus-infected brain preparations.", "content": "Cell fusion was induced by brain extracts containing the scrapie virus and the virus of Creutzfeldt-Jakob disease. The assay involved quantitation of colony-forming ability in a double selection system, strandardized against fusion induced by Sendai virus. Correlation between the logarithm of virus dilution and the hybrid colony number gave similar curves for scrapie virus and Sendai virus. Fusion induction may explain some aspects of pathogenesis in these diseases and provide a potential in vitro assay.", "contents": "Cell fusion induced by scrapie and Creutzfeldt-Jakob virus-infected brain preparations. Cell fusion was induced by brain extracts containing the scrapie virus and the virus of Creutzfeldt-Jakob disease. The assay involved quantitation of colony-forming ability in a double selection system, strandardized against fusion induced by Sendai virus. Correlation between the logarithm of virus dilution and the hybrid colony number gave similar curves for scrapie virus and Sendai virus. Fusion induction may explain some aspects of pathogenesis in these diseases and provide a potential in vitro assay."}
{"id": "PMID:208081", "title": "In vitro isolation of stable rat sarcoma viruses.", "content": "A Sprague-Dawley (SD-1) rat embryo culture, at low passage level, released an endogenous ecotropic type C virus (SD-RaLV) and after about 20 further passages it underwent spontaneous transformation. The SD-RaLV, released from the transformed cells, did not cause rapid transformation of other rat embryo cells. However, when the transformed cells were repeatedly cocultivated with three different chemically transformed and serially transplanted rat tumor cell lines (sarcoma, carcinoma, and hepatoma), rapidly fibroblast-transforming \"sarcoma\" viruses (RaSV) were recovered after each attempt. RaSV was not recovered from one of these tumor cell lines before transplantation, nor could focus-forming virus be rescued from these same tumor cells by cocultivation with other cells releasing heterologous type C viruses. Foci were induced on normal rat kidney and several other rat embryo cell strains within 7-15 days and both productive and nonproductive NRK clones were derived. The productive clones were positive for rat specific p30 antigen and the RaSVs released were serially transmitted to other rat embryo cells. RaSV genome was rescued from the nonproductive clones by superinfection with SD-RaLV, wild rat type C virus, and several heterologous type C viruses. These observations appear to represent naturally occurring transformation-specific (src) genes being recovered in vitro in the form of stable \"sarcoma\" viruses. These viruses differ from the Kirsten and Harvey strains of murine sarcoma virus in that they apparently contain no MuLV sequences and are of purely rat origin.", "contents": "In vitro isolation of stable rat sarcoma viruses. A Sprague-Dawley (SD-1) rat embryo culture, at low passage level, released an endogenous ecotropic type C virus (SD-RaLV) and after about 20 further passages it underwent spontaneous transformation. The SD-RaLV, released from the transformed cells, did not cause rapid transformation of other rat embryo cells. However, when the transformed cells were repeatedly cocultivated with three different chemically transformed and serially transplanted rat tumor cell lines (sarcoma, carcinoma, and hepatoma), rapidly fibroblast-transforming \"sarcoma\" viruses (RaSV) were recovered after each attempt. RaSV was not recovered from one of these tumor cell lines before transplantation, nor could focus-forming virus be rescued from these same tumor cells by cocultivation with other cells releasing heterologous type C viruses. Foci were induced on normal rat kidney and several other rat embryo cell strains within 7-15 days and both productive and nonproductive NRK clones were derived. The productive clones were positive for rat specific p30 antigen and the RaSVs released were serially transmitted to other rat embryo cells. RaSV genome was rescued from the nonproductive clones by superinfection with SD-RaLV, wild rat type C virus, and several heterologous type C viruses. These observations appear to represent naturally occurring transformation-specific (src) genes being recovered in vitro in the form of stable \"sarcoma\" viruses. These viruses differ from the Kirsten and Harvey strains of murine sarcoma virus in that they apparently contain no MuLV sequences and are of purely rat origin."}
{"id": "PMID:208082", "title": "Ultrastructural localization of gamma-aminobutyric acid receptors in the mammalian central nervous system by means of [3H]muscimol binding.", "content": "This study utilizes tritiated muscimol binding and electron microscope autoradiography (Ilford L4 emulsion and phenidone development) to localize gamma-aminobutyric acid (GABA) receptor sites in the cerebellum of the rat. In the cerebellar cortex, silver grains were associated with somata and dendrites of basket and stellate cells in the molecular layer, with somata and primary and secondary dendritic shafts of Purkinje cells, axons and terminals of basket cells in the pinceau or basket, initial axonal segments and myelinated axons of Purkinje cells, and dendrites of granule and Golgi cells in the granular layer, and with somata and dendritic shafts of large and small cells in the cerebellar nuclei. These data correspond well to the light-microscope-autoradiographic observations in the cerebellum previously reported [Chan-Palay, V. (1978) Proc. Natl. Acad. Sci. 75, 1024-1028]. Label over GABA receptor sites can be localized to the plasma membranes between pre- and postsynaptic elements at synaptic junctions, of which 88.9% of the samples are axodendritic and the remaining 11.1% are axosomatic. GABA receptor sites are also found along axonal membranes of the GABA-containing basket cell within the basket surrounding Purkinje cells, where true axo-axonal synapses are rare. It is speculated that GABA receptors in the basket may suggest a possibility of the basis for synchronization, either self-inhibition or facilitation within the basket formation, or presynaptic suppression of inhibitory action of basket cell on Purkinje cell.", "contents": "Ultrastructural localization of gamma-aminobutyric acid receptors in the mammalian central nervous system by means of [3H]muscimol binding. This study utilizes tritiated muscimol binding and electron microscope autoradiography (Ilford L4 emulsion and phenidone development) to localize gamma-aminobutyric acid (GABA) receptor sites in the cerebellum of the rat. In the cerebellar cortex, silver grains were associated with somata and dendrites of basket and stellate cells in the molecular layer, with somata and primary and secondary dendritic shafts of Purkinje cells, axons and terminals of basket cells in the pinceau or basket, initial axonal segments and myelinated axons of Purkinje cells, and dendrites of granule and Golgi cells in the granular layer, and with somata and dendritic shafts of large and small cells in the cerebellar nuclei. These data correspond well to the light-microscope-autoradiographic observations in the cerebellum previously reported [Chan-Palay, V. (1978) Proc. Natl. Acad. Sci. 75, 1024-1028]. Label over GABA receptor sites can be localized to the plasma membranes between pre- and postsynaptic elements at synaptic junctions, of which 88.9% of the samples are axodendritic and the remaining 11.1% are axosomatic. GABA receptor sites are also found along axonal membranes of the GABA-containing basket cell within the basket surrounding Purkinje cells, where true axo-axonal synapses are rare. It is speculated that GABA receptors in the basket may suggest a possibility of the basis for synchronization, either self-inhibition or facilitation within the basket formation, or presynaptic suppression of inhibitory action of basket cell on Purkinje cell."}
{"id": "PMID:208083", "title": "alpha-Bungarotoxin blocks nicotinic transmission in the avian ciliary ganglion.", "content": "alpha-Bungarotoxin binds to nicotinic receptors in skeletal muscle, blocking neuromuscular transmission. Because this toxin has recently been shown to bind to chicken ciliary ganglia, an attempt has been made to determine whether it also blocks nicotinic transmission in this ganglion, alpha-Bungarotoxin (1 micrometer) completely blocked nicotinic transmission in both the ciliary and choroid neurons of chicken and pigeon ciliary ganglia. The effect of the toxin could be partially reversed by prolonged washing (2--8 hr). Incubation of ganglia with d-tubocurarine (0.1 mM) prior to the addition of alpha-bungarotoxin significantly decreased the duration of the washout period necessary to restore transmission. These results suggest that d-tubocurarine and alpha-bungarotoxin are interacting with the same receptor. Under similar conditions, alpha-bungarotoxin did not block nicotinic transmission in the rat superior cervical ganglion, in agreement with previous reports. The avian ciliary ganglion is the only vertebrate autonomic ganglion in which both alpha-bungarotoxin binding and alpha-bungarotoxin blockade of transmission have been shown to occur. This ganglion therefore provides a model system for using alpha-bungarotoxin to study neuronal nicotinic receptors.", "contents": "alpha-Bungarotoxin blocks nicotinic transmission in the avian ciliary ganglion. alpha-Bungarotoxin binds to nicotinic receptors in skeletal muscle, blocking neuromuscular transmission. Because this toxin has recently been shown to bind to chicken ciliary ganglia, an attempt has been made to determine whether it also blocks nicotinic transmission in this ganglion, alpha-Bungarotoxin (1 micrometer) completely blocked nicotinic transmission in both the ciliary and choroid neurons of chicken and pigeon ciliary ganglia. The effect of the toxin could be partially reversed by prolonged washing (2--8 hr). Incubation of ganglia with d-tubocurarine (0.1 mM) prior to the addition of alpha-bungarotoxin significantly decreased the duration of the washout period necessary to restore transmission. These results suggest that d-tubocurarine and alpha-bungarotoxin are interacting with the same receptor. Under similar conditions, alpha-bungarotoxin did not block nicotinic transmission in the rat superior cervical ganglion, in agreement with previous reports. The avian ciliary ganglion is the only vertebrate autonomic ganglion in which both alpha-bungarotoxin binding and alpha-bungarotoxin blockade of transmission have been shown to occur. This ganglion therefore provides a model system for using alpha-bungarotoxin to study neuronal nicotinic receptors."}
{"id": "PMID:208089", "title": "Affinity labeling of a cell surface receptor for epidermal growth factor.", "content": "The membrane receptor for epidermal growth factor (EGF) on 3T3 cells has been identified and specifically labeled radiochemically using a photoreactive derivative of EGF. Photoreactive EGF, labeled with 125I, was incubated with 3T3 cells and then photolyzed in situ to generate a nitrene capable of reacting with a wide variety of chemical bonds. Analysis of the system by sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed, besides the band of EGF, only 1 other major radioactive band which migrated at approximately 190,000 daltons. This band was absent when a nonresponsive and nonbinding variant of 3T3 was used. A direct proportionality between binding activity and crosslinked complex formation was demonstrated using a variety of binding conditions. The crosslinked complex in intact cells is accessible to the action of a macromolecule like trypsin at 4 degrees, suggesting a cell surface location for this complex. Upon incubation of cells at 37 degrees, radioactivity from previously formed EGF-receptor crosslinked complex is converted by cellular action to 3 forms of mol wt less than or equal to 58,000 daltons. These are not accessible to trypsin action upon intact cells.", "contents": "Affinity labeling of a cell surface receptor for epidermal growth factor. The membrane receptor for epidermal growth factor (EGF) on 3T3 cells has been identified and specifically labeled radiochemically using a photoreactive derivative of EGF. Photoreactive EGF, labeled with 125I, was incubated with 3T3 cells and then photolyzed in situ to generate a nitrene capable of reacting with a wide variety of chemical bonds. Analysis of the system by sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed, besides the band of EGF, only 1 other major radioactive band which migrated at approximately 190,000 daltons. This band was absent when a nonresponsive and nonbinding variant of 3T3 was used. A direct proportionality between binding activity and crosslinked complex formation was demonstrated using a variety of binding conditions. The crosslinked complex in intact cells is accessible to the action of a macromolecule like trypsin at 4 degrees, suggesting a cell surface location for this complex. Upon incubation of cells at 37 degrees, radioactivity from previously formed EGF-receptor crosslinked complex is converted by cellular action to 3 forms of mol wt less than or equal to 58,000 daltons. These are not accessible to trypsin action upon intact cells."}
{"id": "PMID:208090", "title": "Effect of haemagglutinating virus of Japan on the potassium compartmentation and the membrane potential of human erythrocytes.", "content": "HVJ induces release of potassium and changes in membrane potential of certain types of cells. These changes are quite dependent on incubation temperature and are inhibited by the addition of con A to cell suspensions prior to the addition of viruses.", "contents": "Effect of haemagglutinating virus of Japan on the potassium compartmentation and the membrane potential of human erythrocytes. HVJ induces release of potassium and changes in membrane potential of certain types of cells. These changes are quite dependent on incubation temperature and are inhibited by the addition of con A to cell suspensions prior to the addition of viruses."}
{"id": "PMID:208091", "title": "Reduction mammaplasty with discovery of occult breast carcinoma in twins: case reports.", "content": "A pair of twins is presented in whom breast carcinomas were found. A reduction mammaplasty in the first twin uncovered an occult intraductal carcinoma. Subcutaneous mastectomies were then done in both twins for identical, mirror-image lesions, The first twin subsequently required a radical mastectomy on the involved side.", "contents": "Reduction mammaplasty with discovery of occult breast carcinoma in twins: case reports. A pair of twins is presented in whom breast carcinomas were found. A reduction mammaplasty in the first twin uncovered an occult intraductal carcinoma. Subcutaneous mastectomies were then done in both twins for identical, mirror-image lesions, The first twin subsequently required a radical mastectomy on the involved side."}
{"id": "PMID:208092", "title": "Burn syndactyly.", "content": "When the entire digital web space has been destroyed by burn scarring and there is a contracture of the volar aspect of the web as well as the dorsum, Z-plasties and skin grafts alone seldom produce a satisfactory web space. During the past 3 years, for the release of 46 contracted web spaces in 20 burned patients, we have turned a rectangular flap from the dorsal surface of the web through into an inverted-T incision in the palm. The adjacent sides of the defects have been skin grafted. In all these patients, we obtained satisfactory release of the contracture and restoration of the web space.", "contents": "Burn syndactyly. When the entire digital web space has been destroyed by burn scarring and there is a contracture of the volar aspect of the web as well as the dorsum, Z-plasties and skin grafts alone seldom produce a satisfactory web space. During the past 3 years, for the release of 46 contracted web spaces in 20 burned patients, we have turned a rectangular flap from the dorsal surface of the web through into an inverted-T incision in the palm. The adjacent sides of the defects have been skin grafted. In all these patients, we obtained satisfactory release of the contracture and restoration of the web space."}
{"id": "PMID:208098", "title": "Cholangiographic abnormalities in patients with inflammatory bowel disease.", "content": "Twenty patients with inflammatory bowel disease, abnormal liver function tests and abnormal endoscopic retrograde cholangiograms were found to have a spectrum of abnormalities affecting the intra- and extrahepatic biliary trees. The intrahepatic systems were abnormal in all patients and demonstrated ductal stenosis, ectasia, decreased arborization and major duct obstruction. The extrahepatic systems were abnormal in 75 percent of cases with stenosis, diverticula formation and mural irregularity being the most frequent abnormalities. The value of endoscopic retrograde cholangiography in this patient group is to exclude extrahepatic obstruction, establish a nonoperative diagnosis, and assist in determining the method of treatment.", "contents": "Cholangiographic abnormalities in patients with inflammatory bowel disease. Twenty patients with inflammatory bowel disease, abnormal liver function tests and abnormal endoscopic retrograde cholangiograms were found to have a spectrum of abnormalities affecting the intra- and extrahepatic biliary trees. The intrahepatic systems were abnormal in all patients and demonstrated ductal stenosis, ectasia, decreased arborization and major duct obstruction. The extrahepatic systems were abnormal in 75 percent of cases with stenosis, diverticula formation and mural irregularity being the most frequent abnormalities. The value of endoscopic retrograde cholangiography in this patient group is to exclude extrahepatic obstruction, establish a nonoperative diagnosis, and assist in determining the method of treatment."}
{"id": "PMID:208099", "title": "Dose-time relationships and the local control of small cell carcinoma of the lung.", "content": "Since 1971, 66 patients with small cell carcinoma of the lung--32 with limited and 34 with disseminated disease--have received irradiation to the primary tumor. There were 20 local failures, 90% of which were apparent within 30 weeks of the start of irradiation. Patients were treated with local irradiation only (32), irradiation plus combination chemotherapy (25), or local plus total body irradiation (9). With local irradiation alone, tumor control increased with increasing biologic dose. When chemotherapy or total body irradiation was added, doses of irradiation that were otherwise insufficient for local control proved to be effective.", "contents": "Dose-time relationships and the local control of small cell carcinoma of the lung. Since 1971, 66 patients with small cell carcinoma of the lung--32 with limited and 34 with disseminated disease--have received irradiation to the primary tumor. There were 20 local failures, 90% of which were apparent within 30 weeks of the start of irradiation. Patients were treated with local irradiation only (32), irradiation plus combination chemotherapy (25), or local plus total body irradiation (9). With local irradiation alone, tumor control increased with increasing biologic dose. When chemotherapy or total body irradiation was added, doses of irradiation that were otherwise insufficient for local control proved to be effective."}
{"id": "PMID:208100", "title": "Endotracheal irradiation of adenoid cystic carcinoma of the trachea.", "content": "Management of advanced or recurrent primary tracheal neoplasms has been restricted to palliative external beam irradiation. A patient with recurrent adenoid cystic carcinoma of the trachea was recently treated again by combined external irradiation and endotracheal brachytherapy with iridium 192 sources; the results were dramatic without significant normal tissue toxicity. This endotracheal brachytherapy technique might be applied to tracheal tumors of different histology or more limited extent.", "contents": "Endotracheal irradiation of adenoid cystic carcinoma of the trachea. Management of advanced or recurrent primary tracheal neoplasms has been restricted to palliative external beam irradiation. A patient with recurrent adenoid cystic carcinoma of the trachea was recently treated again by combined external irradiation and endotracheal brachytherapy with iridium 192 sources; the results were dramatic without significant normal tissue toxicity. This endotracheal brachytherapy technique might be applied to tracheal tumors of different histology or more limited extent."}
{"id": "PMID:208101", "title": "The air meniscus sign in sclerosing hemangioma of the lung.", "content": "The air meniscus sign occurs in a number of lung conditions, including infection, benign and malignant tumors, and hematoma. Sclerosing hemangioma does not appear to have been implicated previously in this connection. Two such cases are described. Possible mechanisms of air meniscus formation and its diagnostic value in sclerosing hemangioma are discussed.", "contents": "The air meniscus sign in sclerosing hemangioma of the lung. The air meniscus sign occurs in a number of lung conditions, including infection, benign and malignant tumors, and hematoma. Sclerosing hemangioma does not appear to have been implicated previously in this connection. Two such cases are described. Possible mechanisms of air meniscus formation and its diagnostic value in sclerosing hemangioma are discussed."}
{"id": "PMID:208102", "title": "The Klippel-Trenaunay syndrome: clinical and radiological aspects.", "content": "Klippel-Trenaunay syndrome (KTS) is characterized by port-wine hemangiomas, deep venous system abnormalities, superficial varicosities, and bony and soft-tissue hypertrophy. When associated with an arteriovenous fistula, it has been termed Klippel-Trenaunay-Parkes-Weber syndrome. It is imperative that both the radiologist and surgeon be aware of this entity, as incomplete evaluation and inappropriate surgery may be devastating. Radiological workup includes phlebography, angiography, and conventional radiography of the involved extremities. Surgery should be performed only to relieve deep venous obstruction (if present) or to correct inequality in the lengths of legs. Removal of superficial varicosities is contraindicated because it will worsen existing symptoms. Five cases of KTS are presented and the literature reviewed.", "contents": "The Klippel-Trenaunay syndrome: clinical and radiological aspects. Klippel-Trenaunay syndrome (KTS) is characterized by port-wine hemangiomas, deep venous system abnormalities, superficial varicosities, and bony and soft-tissue hypertrophy. When associated with an arteriovenous fistula, it has been termed Klippel-Trenaunay-Parkes-Weber syndrome. It is imperative that both the radiologist and surgeon be aware of this entity, as incomplete evaluation and inappropriate surgery may be devastating. Radiological workup includes phlebography, angiography, and conventional radiography of the involved extremities. Surgery should be performed only to relieve deep venous obstruction (if present) or to correct inequality in the lengths of legs. Removal of superficial varicosities is contraindicated because it will worsen existing symptoms. Five cases of KTS are presented and the literature reviewed."}
{"id": "PMID:208109", "title": "[Cellular hypersensitivity in the infection of mice by Junin virus. I. Passive transfer].", "content": "The data presented confirm previous evidence of delayed hypersensitivity in mice following infection with Junin virus. Adaptive transfer of sensitized cells from adult mice which had received 5 Junin virus injections into preinfected newborn mice shortened their survival by 72 hours. It was clear, however, that the development of the immunological mechanism in adult mice occurred under certain conditions. This evidence was confirmed by the observations that the induction of cell-mediated immunity and the response of sensitized lymphocytes to viral antigens appeared to be related to multiple injections of the virus. On the other hand, the sensitized cells were present in adult mice by day 9 and vanished 60 days after the infection. These results revealed the difference between the lymphoid cells from adult mice in the early and the late stages of immunity. The implications of these results in the development of the fatal neurological disease induced by the Junin virus in newborn mice are discussed.", "contents": "[Cellular hypersensitivity in the infection of mice by Junin virus. I. Passive transfer]. The data presented confirm previous evidence of delayed hypersensitivity in mice following infection with Junin virus. Adaptive transfer of sensitized cells from adult mice which had received 5 Junin virus injections into preinfected newborn mice shortened their survival by 72 hours. It was clear, however, that the development of the immunological mechanism in adult mice occurred under certain conditions. This evidence was confirmed by the observations that the induction of cell-mediated immunity and the response of sensitized lymphocytes to viral antigens appeared to be related to multiple injections of the virus. On the other hand, the sensitized cells were present in adult mice by day 9 and vanished 60 days after the infection. These results revealed the difference between the lymphoid cells from adult mice in the early and the late stages of immunity. The implications of these results in the development of the fatal neurological disease induced by the Junin virus in newborn mice are discussed."}
{"id": "PMID:208110", "title": "[Cellular hypersensitivity in the infection of mice by Junin virus. III. Experience with Cr51 an antitheta serum].", "content": "Several aspects of the appearance and development of delayed hypersensitivity in mice infected with Junin virus are described. The results obtained showed that the development of the immunological mechanisms occurs irrespective of age. Spleen cells of donor mice inoculated with one i.p. dose of Junin virus had a poor cytotoxic activity, as demonstrated by 51Cr release and adoptive immunity procedures. Spleen cells treated with anti-theta serum and complement did not strikingly affect the development of Junin virus disease in mice. This demonstrated the capacity of T lymphocytes to influence the course of the viral infection of newborn mice adoptively transferred with immune spleen cells. No difference were detected in the virus titer in the brains of transferred and control animals, this fact suggests that immune T lymphocytes are not involved in Jun\u00edn virus clearance.", "contents": "[Cellular hypersensitivity in the infection of mice by Junin virus. III. Experience with Cr51 an antitheta serum]. Several aspects of the appearance and development of delayed hypersensitivity in mice infected with Junin virus are described. The results obtained showed that the development of the immunological mechanisms occurs irrespective of age. Spleen cells of donor mice inoculated with one i.p. dose of Junin virus had a poor cytotoxic activity, as demonstrated by 51Cr release and adoptive immunity procedures. Spleen cells treated with anti-theta serum and complement did not strikingly affect the development of Junin virus disease in mice. This demonstrated the capacity of T lymphocytes to influence the course of the viral infection of newborn mice adoptively transferred with immune spleen cells. No difference were detected in the virus titer in the brains of transferred and control animals, this fact suggests that immune T lymphocytes are not involved in Jun\u00edn virus clearance."}
{"id": "PMID:208122", "title": "Aldosterone regulation in anephric patients.", "content": "The response of plasma aldosterone to hemodialysis, 3 h orthostatism, K-loading and angiotensin II and ACTH infusions has been studied. Hemodialysis, orthostatism and angiotensin II infusion do not modify aldosterone levels. By the contrary ACTH and potassium originate a significant increase in plasma aldosterone. They seem to be the main aldosterone secretion regulators in the absence of renin production.", "contents": "Aldosterone regulation in anephric patients. The response of plasma aldosterone to hemodialysis, 3 h orthostatism, K-loading and angiotensin II and ACTH infusions has been studied. Hemodialysis, orthostatism and angiotensin II infusion do not modify aldosterone levels. By the contrary ACTH and potassium originate a significant increase in plasma aldosterone. They seem to be the main aldosterone secretion regulators in the absence of renin production."}
{"id": "PMID:208123", "title": "Acetylcholinesterase from Wistar rat brain.", "content": "Acetylcholinesterase (E.C.3.1.1.7) was partially purified from rat brains stored in toluene. Extraction was performed using buffers containing non-ionic tensoactive detergents. Some properties of the enzyme were affected by the use of different activity measurement methods, such as the short-time radiometric or the long-time colorimetric method. There were two zones of maximum activity in the range pH 7.5-8.0 and 8.0-8.6, respectively. There seems to be a histidine residue in the enzyme that participates in the catalytic process. Thermal denuration presented first order kinetics and different thermodynamic parameters were obtained on using different incubation periods. On using the short-time activity measurement method there was activation at high substrate concentration, but with the long time method there was a marked inhibition produced by excess of substrate. However, if the enzyme was extracted from fresh rat brain, toluene untreated, these differences dissapeared. Gel filtration and disc electrophoresis showed the presence of multiple and interconvertible forms of the enzyme.", "contents": "Acetylcholinesterase from Wistar rat brain. Acetylcholinesterase (E.C.3.1.1.7) was partially purified from rat brains stored in toluene. Extraction was performed using buffers containing non-ionic tensoactive detergents. Some properties of the enzyme were affected by the use of different activity measurement methods, such as the short-time radiometric or the long-time colorimetric method. There were two zones of maximum activity in the range pH 7.5-8.0 and 8.0-8.6, respectively. There seems to be a histidine residue in the enzyme that participates in the catalytic process. Thermal denuration presented first order kinetics and different thermodynamic parameters were obtained on using different incubation periods. On using the short-time activity measurement method there was activation at high substrate concentration, but with the long time method there was a marked inhibition produced by excess of substrate. However, if the enzyme was extracted from fresh rat brain, toluene untreated, these differences dissapeared. Gel filtration and disc electrophoresis showed the presence of multiple and interconvertible forms of the enzyme."}
{"id": "PMID:208125", "title": "[Effect of ACTH administration on liberation of testosterone by the Leydig cell (author's transl)].", "content": "The possible r\u00f4le of the Leydig cells ithe changes of testosterone levels induced by ACTH administration is studied. 14 male Wistar rats weighing about 300 g were separated in two groups. One was treated with I mU.I./100 g/day of ACTH i.m. for 6 days and the other with saline solution as control Rats, testes and adrenal glands were weighed and plasma testosterone levels were measured. The Leydig cells dispersed collagenase was inbubated for 120 min at 37 degrees C in the presence and in the absence of 10 mU.I. of HCG. The weight of adrenal glands in the treated rats was greater than in the control group. Treated rats had lower plasma values than the controls. Testosterone secretion by the Leydig cells, in basal situation and after stimulation with HCG, was lower in the treated group. Leydig cells of untreated rats were incubated with 12.5, 6.2, 3.1, 1.5 mU.I. of ACTH and supplemented with 2.5 pU.I. of HCG. No difference in testosterone secretion in either groups was observed.", "contents": "[Effect of ACTH administration on liberation of testosterone by the Leydig cell (author's transl)]. The possible r\u00f4le of the Leydig cells ithe changes of testosterone levels induced by ACTH administration is studied. 14 male Wistar rats weighing about 300 g were separated in two groups. One was treated with I mU.I./100 g/day of ACTH i.m. for 6 days and the other with saline solution as control Rats, testes and adrenal glands were weighed and plasma testosterone levels were measured. The Leydig cells dispersed collagenase was inbubated for 120 min at 37 degrees C in the presence and in the absence of 10 mU.I. of HCG. The weight of adrenal glands in the treated rats was greater than in the control group. Treated rats had lower plasma values than the controls. Testosterone secretion by the Leydig cells, in basal situation and after stimulation with HCG, was lower in the treated group. Leydig cells of untreated rats were incubated with 12.5, 6.2, 3.1, 1.5 mU.I. of ACTH and supplemented with 2.5 pU.I. of HCG. No difference in testosterone secretion in either groups was observed."}
{"id": "PMID:208121", "title": "[The E.E.G. and E.M.G. findings in sudanophilic leucodystrophy (author's transl)].", "content": "Four patients with infantile familial sudanophilic leucodystrophy confirmed histologically and biochemically were investigated by E.E.G. and E.M.G. The E.E.G. showed a severe, non-specific slow wave abnormality, of moderate voltage and disorganized in 2 cases, with some critical' tonic' discharge. E.M.G. study was normal in relaxed muscle; peripheral nerve stimulation, however, revealed marked slowing of motor conduction velocities favouring a segmental demyelinisation process, which was ultimately confirmed histologically. This study underlines the value of investigation of infantile encephalopathies.", "contents": "[The E.E.G. and E.M.G. findings in sudanophilic leucodystrophy (author's transl)]. Four patients with infantile familial sudanophilic leucodystrophy confirmed histologically and biochemically were investigated by E.E.G. and E.M.G. The E.E.G. showed a severe, non-specific slow wave abnormality, of moderate voltage and disorganized in 2 cases, with some critical' tonic' discharge. E.M.G. study was normal in relaxed muscle; peripheral nerve stimulation, however, revealed marked slowing of motor conduction velocities favouring a segmental demyelinisation process, which was ultimately confirmed histologically. This study underlines the value of investigation of infantile encephalopathies."}
{"id": "PMID:208126", "title": "Lack of tumor-promoting ability of certain environmental chemicals in a two-stage mouse skin tumorigenesis assay.", "content": "The food antioxidants butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) were tested as tumor promoters on CD1 female mice initiated with 7, 12-dimethylbenz(a)anthracene (DMBA). At a dose of 1 mg twice weekly they did not promote skin tumors. Nor did they produce tumors when tested as a complete carcinogen without DMBA initiation. The polychlorinated biphenyl Aroclor 1254 (PCB) and the polybrominated biphenyl Firemaster-6 (PBB) were also tested for their ability to promote skin tumors; at a 100 microgram dose twice weekly they were inactive. The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at a dose of 0.1 microgram twice weekly did not promote skin tumors in DMBA-initiated mice. TCDD, PCB, and PBB did not promote spontaneous tumors. None of the compounds at the dosages tested significantly increased the intrafollicular epidermis, nor did they appear to be chronically toxic to the test animals. These results indicate that dosage may be an important factor in promotion, since several of the tested compounds are known to be promoters in pulmonary and hepatic systems.", "contents": "Lack of tumor-promoting ability of certain environmental chemicals in a two-stage mouse skin tumorigenesis assay. The food antioxidants butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) were tested as tumor promoters on CD1 female mice initiated with 7, 12-dimethylbenz(a)anthracene (DMBA). At a dose of 1 mg twice weekly they did not promote skin tumors. Nor did they produce tumors when tested as a complete carcinogen without DMBA initiation. The polychlorinated biphenyl Aroclor 1254 (PCB) and the polybrominated biphenyl Firemaster-6 (PBB) were also tested for their ability to promote skin tumors; at a 100 microgram dose twice weekly they were inactive. The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at a dose of 0.1 microgram twice weekly did not promote skin tumors in DMBA-initiated mice. TCDD, PCB, and PBB did not promote spontaneous tumors. None of the compounds at the dosages tested significantly increased the intrafollicular epidermis, nor did they appear to be chronically toxic to the test animals. These results indicate that dosage may be an important factor in promotion, since several of the tested compounds are known to be promoters in pulmonary and hepatic systems."}
{"id": "PMID:208127", "title": "Influence of bile acids and free fatty acids on physicochemical properties of LP-X.", "content": "In this study it is demonstrated, that incubation of both, bile acids and free fatty acids with LP-X, the abnormal plasmalipoprotein found in patients suffering from cholestasis or LCAT-deficiency, results in striking alterations of the physico-chemical and immunological properties of LP-X: 1. The cathodic mobility in agar is changed into an anodic mairation of the material. 2. The unique appearance of LP-X on electronmicrographs is altered by the incubation revealing fingerprint like structures. 3. The albumin portion of LP-X becomes immunologically detectable. 4. Bile salts cause marked changes in the hydrated density of the material as determined by zonal ultracentrifugation. 5. In vitro incubation of LP-X with postheparin plasma causes a complete disappearance of LP-X as judged by its typical migration on agar electrophoresis. All these alterations can be prevented or reversed by the addition of albumin in appropriate concentrations. These findinga are important in the light of studies designed to investigate the catabolic action of plasma lipolytic enzymes on LP-X, as well as for follow up studies of LP-X concentrations during the course of disease.", "contents": "Influence of bile acids and free fatty acids on physicochemical properties of LP-X. In this study it is demonstrated, that incubation of both, bile acids and free fatty acids with LP-X, the abnormal plasmalipoprotein found in patients suffering from cholestasis or LCAT-deficiency, results in striking alterations of the physico-chemical and immunological properties of LP-X: 1. The cathodic mobility in agar is changed into an anodic mairation of the material. 2. The unique appearance of LP-X on electronmicrographs is altered by the incubation revealing fingerprint like structures. 3. The albumin portion of LP-X becomes immunologically detectable. 4. Bile salts cause marked changes in the hydrated density of the material as determined by zonal ultracentrifugation. 5. In vitro incubation of LP-X with postheparin plasma causes a complete disappearance of LP-X as judged by its typical migration on agar electrophoresis. All these alterations can be prevented or reversed by the addition of albumin in appropriate concentrations. These findinga are important in the light of studies designed to investigate the catabolic action of plasma lipolytic enzymes on LP-X, as well as for follow up studies of LP-X concentrations during the course of disease."}
{"id": "PMID:208128", "title": "Hydrogen sulfide: effects on avian respiratory control and intrapulmonary CO2 receptors.", "content": "The respiratory response to acute inhalation of hydrogen sulfide (H2S) and the response of pulmonary CO2 receptors to this gas were studied in male White Leghorn chickens. Inhaling low concentrations of H2S (0.05%) for 30 min had no effect on ventilation, but respiratory frequency and tidal volume became irregular and variable in birds that inhaled 0.2% and 0.3% H2S for that period. All birds that inhaled 0.4% H2S died within 15 min. H2S, presented in the gas stream of unidirectionally ventilated birds, caused an increase in the discharge frequency of intrapulmonary CO2 receptors and an increase in the amplitude of sternal movements. Because an increase in the discharge of these receptors normally inhibits the central respiratory neurons and may lead to apnea, it is clear that H2S also has actions that increase the output from these central neurons. The possibility that H2S affects the intrapulmonary CO2 receptors by inhibiting carbonic anhydrase in them is discussed.", "contents": "Hydrogen sulfide: effects on avian respiratory control and intrapulmonary CO2 receptors. The respiratory response to acute inhalation of hydrogen sulfide (H2S) and the response of pulmonary CO2 receptors to this gas were studied in male White Leghorn chickens. Inhaling low concentrations of H2S (0.05%) for 30 min had no effect on ventilation, but respiratory frequency and tidal volume became irregular and variable in birds that inhaled 0.2% and 0.3% H2S for that period. All birds that inhaled 0.4% H2S died within 15 min. H2S, presented in the gas stream of unidirectionally ventilated birds, caused an increase in the discharge frequency of intrapulmonary CO2 receptors and an increase in the amplitude of sternal movements. Because an increase in the discharge of these receptors normally inhibits the central respiratory neurons and may lead to apnea, it is clear that H2S also has actions that increase the output from these central neurons. The possibility that H2S affects the intrapulmonary CO2 receptors by inhibiting carbonic anhydrase in them is discussed."}
{"id": "PMID:208137", "title": "Harvesting of granulocytes for transfusion therapy by haemonetics 30. Yield, morphology and in vitro functions of collected granulocytes.", "content": "By means of a Haemonetics 30 blood cell separator white blood cells (WBC) were collected for transfusion purposes from 21 normal unstimulated donors. Citrated Hydroxyethyl Starch (HES) was used as anticoagulant. A mean yield of 1.13 x 10(10) WBC was obtained in 2 1/2-3 h. Half of the collected WBC were PMN cells containing a few per cent band forms, the other half lymphocytes and monocytes (12%). No shift in the distribution of WBC was found during the leucapheresis. Light and electron microscopy did not reveal any damage or changes in the structure of the processed granulocytes. The Trypan blue exclusion test showed 99% vital cells. In vitro assessment of the chemotactic and bactericidal activity of the collected granulocytes showed normal function. Also the content of myeloperoxidase was within normal range.", "contents": "Harvesting of granulocytes for transfusion therapy by haemonetics 30. Yield, morphology and in vitro functions of collected granulocytes. By means of a Haemonetics 30 blood cell separator white blood cells (WBC) were collected for transfusion purposes from 21 normal unstimulated donors. Citrated Hydroxyethyl Starch (HES) was used as anticoagulant. A mean yield of 1.13 x 10(10) WBC was obtained in 2 1/2-3 h. Half of the collected WBC were PMN cells containing a few per cent band forms, the other half lymphocytes and monocytes (12%). No shift in the distribution of WBC was found during the leucapheresis. Light and electron microscopy did not reveal any damage or changes in the structure of the processed granulocytes. The Trypan blue exclusion test showed 99% vital cells. In vitro assessment of the chemotactic and bactericidal activity of the collected granulocytes showed normal function. Also the content of myeloperoxidase was within normal range."}
{"id": "PMID:208134", "title": "[Changes in the monosynaptic reflex during wakefulness and sleep of children with cerebral paralysis].", "content": "Changes of the H reflex during sleep were studied in 13 children with cerebral palsy (8 with spastic tetraplegia, 2 with a mixed form of cerebral palsy without spasticity, 3 with hypotonic diplegia or tetraplegia). These modifications were compared with those of 5 normal children of the same age. During repeated night recordings, responses in the calf muscle elicited by electrical stimuli to the posterior tibial nerve were studied at the same time as the EEG, EOG and EMG of the mental muscles. The results show that:--in normal children the max H reflex progressively decreases in amplitude from wakefulness to REM sleep; -- in spastic patients there is only a slight decrease in the H reflex in NREM sleep and no significant change in REM sleep; the amplitude of the H reflex is always greater than that in the control group; -- in the dystonic and hypotonic group the results obtained are similar to those of the control group. From these results one may draw the conclusion that in spastic patients as opposed to the control, dystonic and hypotonic groups, normal balance between the function of supraspinal systems regulating the amplitude of the spinal reflexes is alterated probably through the scarce functionality of the supraspinal inhibitory structures.", "contents": "[Changes in the monosynaptic reflex during wakefulness and sleep of children with cerebral paralysis]. Changes of the H reflex during sleep were studied in 13 children with cerebral palsy (8 with spastic tetraplegia, 2 with a mixed form of cerebral palsy without spasticity, 3 with hypotonic diplegia or tetraplegia). These modifications were compared with those of 5 normal children of the same age. During repeated night recordings, responses in the calf muscle elicited by electrical stimuli to the posterior tibial nerve were studied at the same time as the EEG, EOG and EMG of the mental muscles. The results show that:--in normal children the max H reflex progressively decreases in amplitude from wakefulness to REM sleep; -- in spastic patients there is only a slight decrease in the H reflex in NREM sleep and no significant change in REM sleep; the amplitude of the H reflex is always greater than that in the control group; -- in the dystonic and hypotonic group the results obtained are similar to those of the control group. From these results one may draw the conclusion that in spastic patients as opposed to the control, dystonic and hypotonic groups, normal balance between the function of supraspinal systems regulating the amplitude of the spinal reflexes is alterated probably through the scarce functionality of the supraspinal inhibitory structures."}
{"id": "PMID:208138", "title": "Demonstration of electrophoretically restricted virus-specific antibodies in serum and cerebrospinal fluid by imprint electroimmunofixation.", "content": "A sensitive technique for the electrophoretic characterization of virus-specific antibodies is described. Electrophoretically separated Ig is allowed to diffuse into a virus-antigen containing gel. The antibodies bound to viral antigen are then demonstrated by 125I-labelled rabbit antihuman Ig and autoradiography. Electrophoretically restricted antibodies against measles, rubella, mumps or herpes simplex viruses were demonstrated in some normal sera. The antibody patterns of normal cerebrospinal fluids (CSF) closely resembled those of the matching sera. A selective increase of oligoclonal antibodies was demonstrated in CSF from patients with infection of the central nervous system (CNS) caused by any of the four viruses. We propose that the method may be used to demonstrate local synthesis in the CNS of antibodies against viral or other antigens.", "contents": "Demonstration of electrophoretically restricted virus-specific antibodies in serum and cerebrospinal fluid by imprint electroimmunofixation. A sensitive technique for the electrophoretic characterization of virus-specific antibodies is described. Electrophoretically separated Ig is allowed to diffuse into a virus-antigen containing gel. The antibodies bound to viral antigen are then demonstrated by 125I-labelled rabbit antihuman Ig and autoradiography. Electrophoretically restricted antibodies against measles, rubella, mumps or herpes simplex viruses were demonstrated in some normal sera. The antibody patterns of normal cerebrospinal fluids (CSF) closely resembled those of the matching sera. A selective increase of oligoclonal antibodies was demonstrated in CSF from patients with infection of the central nervous system (CNS) caused by any of the four viruses. We propose that the method may be used to demonstrate local synthesis in the CNS of antibodies against viral or other antigens."}
{"id": "PMID:208139", "title": "[Primary hyperparthyroidism. Analysis of 152 patients with special reference to acute life threatening complications (acute hyperparathyroidism)].", "content": "The findings of 152 patients with proven primary hyperparathyroidism are reportedmthe purpose of the analysis was to find difference between the various clinical manifestations of the disease. Furthermore the occurrence of acute hyperparathyroid crisis in our series as well as in the literature are described. 65.8% of the patients were females, 34.2% were males. The leading symptom in 98 patients (group I) were kidney stones and in 23 patients (group II) cystic bone disease. Both manifestations of the disease occurred in only 7 patients (group III) and no symptoms related to the kidneys or to the bones occurred in 24 patients (group IV). Because of the difference of the clinical manifestations the additional data were analyzed for each group separately and compared with each other. There was no difference in the mean serum calcium levels for all four groups, however, patients of group I were on the average younger, the duration of the disease was longer and the weight of the parathyroid adenoma was lower compared to the other three groups, Data are presented regarding calcium excretion, phosphate clearance and tubular reabsorption of phosphate for each group. At operation single or multiple adenoma formation was present in 133 patients, whereas diffuse hyperplasia was found in 17 and carcinoma in 2 other patients. 46 of the adenomas were found in an atypical anatomical localisation. This observation is responsible for the many unsuccessful or second explorations of the neck; The weight of the adenomas varied between 0.1 and 23.5 g. The most difficult diagnosis was that of diffuse hyperplasia. The sucess of the surgical intervention was usually established in over 80% of the cases within 24 to 48 hours after the operation with a significant fall of serum calcium. There ist still no definite explanation for the variability of the clinical manifestations of primary hyperparathyroidism. Parathyroid hormone determinations on larger numbers of patients are not yet published. The assumption, that different hormones or peptide fragments are reposible for the different action on bone and kidney is discussed; In our series of 152 patients acute hyperparathyroid crisis occurred eight times. Our findings are compared to the other well documented cases in the literature. Main symptoms were nausea, vomiting, abdominal pain and different states of cerebral dysfunction. Most of the patients had calcium levels over 16 mg/100 ml. Partial renal insufficiency with elevated blood urea and phosphate retention was found in over 50% of the cases. Overall mortality of all cases with acute parathyroid crisis is 52.5%. The pathogenesis of acute hyperparathyroidism and the implications of high calcium levels are discussed. According to our own experience hypercalcenia can be controlled with an intensive therapeutic program and emergency operation for acute parathyroid crisis is no longer necessary.", "contents": "[Primary hyperparthyroidism. Analysis of 152 patients with special reference to acute life threatening complications (acute hyperparathyroidism)]. The findings of 152 patients with proven primary hyperparathyroidism are reportedmthe purpose of the analysis was to find difference between the various clinical manifestations of the disease. Furthermore the occurrence of acute hyperparathyroid crisis in our series as well as in the literature are described. 65.8% of the patients were females, 34.2% were males. The leading symptom in 98 patients (group I) were kidney stones and in 23 patients (group II) cystic bone disease. Both manifestations of the disease occurred in only 7 patients (group III) and no symptoms related to the kidneys or to the bones occurred in 24 patients (group IV). Because of the difference of the clinical manifestations the additional data were analyzed for each group separately and compared with each other. There was no difference in the mean serum calcium levels for all four groups, however, patients of group I were on the average younger, the duration of the disease was longer and the weight of the parathyroid adenoma was lower compared to the other three groups, Data are presented regarding calcium excretion, phosphate clearance and tubular reabsorption of phosphate for each group. At operation single or multiple adenoma formation was present in 133 patients, whereas diffuse hyperplasia was found in 17 and carcinoma in 2 other patients. 46 of the adenomas were found in an atypical anatomical localisation. This observation is responsible for the many unsuccessful or second explorations of the neck; The weight of the adenomas varied between 0.1 and 23.5 g. The most difficult diagnosis was that of diffuse hyperplasia. The sucess of the surgical intervention was usually established in over 80% of the cases within 24 to 48 hours after the operation with a significant fall of serum calcium. There ist still no definite explanation for the variability of the clinical manifestations of primary hyperparathyroidism. Parathyroid hormone determinations on larger numbers of patients are not yet published. The assumption, that different hormones or peptide fragments are reposible for the different action on bone and kidney is discussed; In our series of 152 patients acute hyperparathyroid crisis occurred eight times. Our findings are compared to the other well documented cases in the literature. Main symptoms were nausea, vomiting, abdominal pain and different states of cerebral dysfunction. Most of the patients had calcium levels over 16 mg/100 ml. Partial renal insufficiency with elevated blood urea and phosphate retention was found in over 50% of the cases. Overall mortality of all cases with acute parathyroid crisis is 52.5%. The pathogenesis of acute hyperparathyroidism and the implications of high calcium levels are discussed. According to our own experience hypercalcenia can be controlled with an intensive therapeutic program and emergency operation for acute parathyroid crisis is no longer necessary."}
{"id": "PMID:208141", "title": "Heavy metals in tissues of stranded short-finned pilot whales.", "content": "Selected tissues from four short-finned pilot whales that stranded at Cumberland Island National Seashore were analyzed for total cadmium, mercury and selenium by neutron activation. Cadmium reached a maximum mean wet weight concentration of 31.4 ppm in the kidney tissues. Maximum mean wet weight concentrations of mercury, 230.0 ppm, and selenium, 44.2 ppm, were found in the liver tissues. The lowest concentration of each metal was found in the blubber. Postmortem examination showed that the whales had no food in their stomachs. The whales must have been utilizing metabolic reserves, contaminated with residual concentrations of heavy metals, prior to beaching. This utilization of reserves probably resulted in the high concentrations of cadmium, mercury and selenium found in the liver and kidney tissues. Since the heavy metal concentrations were three to four times greater in the stranded whales, as compared to apparently healthy whales of the same species, it is suggested that heavy metal toxicosis may have been a factor contributing to this particular stranding.", "contents": "Heavy metals in tissues of stranded short-finned pilot whales. Selected tissues from four short-finned pilot whales that stranded at Cumberland Island National Seashore were analyzed for total cadmium, mercury and selenium by neutron activation. Cadmium reached a maximum mean wet weight concentration of 31.4 ppm in the kidney tissues. Maximum mean wet weight concentrations of mercury, 230.0 ppm, and selenium, 44.2 ppm, were found in the liver tissues. The lowest concentration of each metal was found in the blubber. Postmortem examination showed that the whales had no food in their stomachs. The whales must have been utilizing metabolic reserves, contaminated with residual concentrations of heavy metals, prior to beaching. This utilization of reserves probably resulted in the high concentrations of cadmium, mercury and selenium found in the liver and kidney tissues. Since the heavy metal concentrations were three to four times greater in the stranded whales, as compared to apparently healthy whales of the same species, it is suggested that heavy metal toxicosis may have been a factor contributing to this particular stranding."}
{"id": "PMID:208143", "title": "Toxic gases from fires.", "content": "The major lethal factors in uncontrolled fires are toxic gases, heat, and oxygen deficiency. The predominant toxic gas is carbon monoxide, which is readily generated from the combusion of wood and other cellulosic materials. Increasing use of a variety of synthetic polymers has stimulated interest in screening tests to evaluated the toxicity of polymeric materials when thermally decomposed. As yet, this country lacks a standardized fire toxicity test protocol.", "contents": "Toxic gases from fires. The major lethal factors in uncontrolled fires are toxic gases, heat, and oxygen deficiency. The predominant toxic gas is carbon monoxide, which is readily generated from the combusion of wood and other cellulosic materials. Increasing use of a variety of synthetic polymers has stimulated interest in screening tests to evaluated the toxicity of polymeric materials when thermally decomposed. As yet, this country lacks a standardized fire toxicity test protocol."}
{"id": "PMID:208144", "title": "Commissural transmission: maturational changes in humans.", "content": "Latency differences between ipsilateral and contralateral somatosensory evoked potentials show maturational trends in keeing with the myelogenic timetable and development of the corpus callosum. The distribution and modality-specific projection of early ipsilateral activity suggests an origin in the contralateral posterior-parietal area.", "contents": "Commissural transmission: maturational changes in humans. Latency differences between ipsilateral and contralateral somatosensory evoked potentials show maturational trends in keeing with the myelogenic timetable and development of the corpus callosum. The distribution and modality-specific projection of early ipsilateral activity suggests an origin in the contralateral posterior-parietal area."}
{"id": "PMID:208145", "title": "beta-Adrenergic receptors in aged rat brain: reduced number and capacity of pineal gland to develop supersensitivity.", "content": "The density but not the affinity of beta-adrenergic receptors declined significantly with age in rat pineal gland, corpus striatum, and cerebellum, as determined by the binding of tritiated dihydroalprenolol. Exposing rats to light for 12 hours increased the binding of this radioligand in 3-month-old but not in 24-month-old rats. The reduced responsiveness to catecholamines seen in aging may be due to a decrease in the number of beta-adrenergic receptors which, in turn, may be caused by an impaired capacity of receptors in aged animals to adapt to changes in adrenergic neuronal input.", "contents": "beta-Adrenergic receptors in aged rat brain: reduced number and capacity of pineal gland to develop supersensitivity. The density but not the affinity of beta-adrenergic receptors declined significantly with age in rat pineal gland, corpus striatum, and cerebellum, as determined by the binding of tritiated dihydroalprenolol. Exposing rats to light for 12 hours increased the binding of this radioligand in 3-month-old but not in 24-month-old rats. The reduced responsiveness to catecholamines seen in aging may be due to a decrease in the number of beta-adrenergic receptors which, in turn, may be caused by an impaired capacity of receptors in aged animals to adapt to changes in adrenergic neuronal input."}
{"id": "PMID:208146", "title": "Investigation of electron tunneling between cytochrome c peroxidase and cytochrome c.", "content": "The nature of electron transfer between the bound complex cytochrome c and cytochrome c peroxidase has been investigated. Experimental verification of the predicted charge-transfer band provides evidence of electron tunneling as the mechanism of transfer between these molecules in solution at room temperature. The measured transfer distance is congruent to 7 angstroms between heme edges, which results in a distance of congruent to 15 to 20 angstroms between iron atoms.", "contents": "Investigation of electron tunneling between cytochrome c peroxidase and cytochrome c. The nature of electron transfer between the bound complex cytochrome c and cytochrome c peroxidase has been investigated. Experimental verification of the predicted charge-transfer band provides evidence of electron tunneling as the mechanism of transfer between these molecules in solution at room temperature. The measured transfer distance is congruent to 7 angstroms between heme edges, which results in a distance of congruent to 15 to 20 angstroms between iron atoms."}
{"id": "PMID:208147", "title": "Rise and fall of cyclic AMP required for onset of lymphocyte DNA synthesis.", "content": "The adenosine 3',5'-monophosphate (cyclic AMP) levels of mouse lymphocytes rose and fell sharply 10 hours after stimulation with concanavalin A. Treatment of the cells with indomethacin reversibly prevented the increase in cyclic AMP and the subsequent onset of DNA synthesis. When the heightened cyclic AMP before S phase was maintained by either inhibiting phosphodiesterase or by adding the 8-bromo derivative of cyclic AMP, DNA synthesis was also blocked. Both the increase and decrease in cyclic AMP appear to be required for progression of lymphocytes into the S phase of growth.", "contents": "Rise and fall of cyclic AMP required for onset of lymphocyte DNA synthesis. The adenosine 3',5'-monophosphate (cyclic AMP) levels of mouse lymphocytes rose and fell sharply 10 hours after stimulation with concanavalin A. Treatment of the cells with indomethacin reversibly prevented the increase in cyclic AMP and the subsequent onset of DNA synthesis. When the heightened cyclic AMP before S phase was maintained by either inhibiting phosphodiesterase or by adding the 8-bromo derivative of cyclic AMP, DNA synthesis was also blocked. Both the increase and decrease in cyclic AMP appear to be required for progression of lymphocytes into the S phase of growth."}
{"id": "PMID:208148", "title": "Acute effects of alcohol on auditory brainstem potentials in humans.", "content": "Auditory brainstem potentials were recorded from human subjects before and after an intoxicating dose of alcohol. Following alcohol ingestion there were significant, progressive increases in the latencies of brainstem potential peaks III through VII. No changes in peak amplitudes were found. The results indicate that alcohol has a depressive effect on neural transmission within the primary auditory brainstem pathway.", "contents": "Acute effects of alcohol on auditory brainstem potentials in humans. Auditory brainstem potentials were recorded from human subjects before and after an intoxicating dose of alcohol. Following alcohol ingestion there were significant, progressive increases in the latencies of brainstem potential peaks III through VII. No changes in peak amplitudes were found. The results indicate that alcohol has a depressive effect on neural transmission within the primary auditory brainstem pathway."}
{"id": "PMID:208149", "title": "Pressure-adaptive differences in lactate dehydrogenases of congeneric fishes living at different depths.", "content": "The muscle-type (M4) lactate dehydrogenases of Sebastolobus altivelis, a deep-water scorpaenid, and S. alascanus, a shallower species, are electrophoretically indistinguishable, yet differ in pressure sensitivities. The lactate dehydrogenase of S. altivelis exhibits lower pressure sensitivities of substrate and coenzyme binding and catalytic rate. Such apparently pressure-adaptive kinetic properties may be important for establishing species depth zonation patterns in the ocean.", "contents": "Pressure-adaptive differences in lactate dehydrogenases of congeneric fishes living at different depths. The muscle-type (M4) lactate dehydrogenases of Sebastolobus altivelis, a deep-water scorpaenid, and S. alascanus, a shallower species, are electrophoretically indistinguishable, yet differ in pressure sensitivities. The lactate dehydrogenase of S. altivelis exhibits lower pressure sensitivities of substrate and coenzyme binding and catalytic rate. Such apparently pressure-adaptive kinetic properties may be important for establishing species depth zonation patterns in the ocean."}
{"id": "PMID:208150", "title": "Enzyme-linked immunosorbent assay for identification of rotaviruses from different animal species.", "content": "Rotaviruses cause gastroenteritis in man and a wide variety of animal species. They cross-react in many immunologic tests and have a similar appearance by electron microscopy, making differentiation among them difficult. Rotaviruses derived from different host species were distinguished by postinfection serum blocking virus activity in an enzyme-linked immunosorbent assay (ELISA). Thirty-three rotavirus isolates from children living in three different parts of the world could not be differentiated by this technique, but they were distinct from four strains recovered from calves, and a series of strains isolated from piglets, foals, monkeys, and infant mice. The four bovine strains were similar, but they could be differentiated from the other animal strains, each of which exhibited a distinct pattern when tested by the ELISA blocking technique.", "contents": "Enzyme-linked immunosorbent assay for identification of rotaviruses from different animal species. Rotaviruses cause gastroenteritis in man and a wide variety of animal species. They cross-react in many immunologic tests and have a similar appearance by electron microscopy, making differentiation among them difficult. Rotaviruses derived from different host species were distinguished by postinfection serum blocking virus activity in an enzyme-linked immunosorbent assay (ELISA). Thirty-three rotavirus isolates from children living in three different parts of the world could not be differentiated by this technique, but they were distinct from four strains recovered from calves, and a series of strains isolated from piglets, foals, monkeys, and infant mice. The four bovine strains were similar, but they could be differentiated from the other animal strains, each of which exhibited a distinct pattern when tested by the ELISA blocking technique."}
{"id": "PMID:208152", "title": "Chemical evolution from hydrogen cyanide: photochemical decarboxylation of orotic acid and orotate derivatives.", "content": "Irradiation of solutions at pH 7 to pH 8.5 of orotic acid, orotidine, and orotidine 5'-phosphate with light at 254 nanometers yields the corresponding uracil derivative via the singlet excited state. This reaction completes a plausible prebiotic synthesis of uracil and its derivatives starting from HCN as the only carbon source.", "contents": "Chemical evolution from hydrogen cyanide: photochemical decarboxylation of orotic acid and orotate derivatives. Irradiation of solutions at pH 7 to pH 8.5 of orotic acid, orotidine, and orotidine 5'-phosphate with light at 254 nanometers yields the corresponding uracil derivative via the singlet excited state. This reaction completes a plausible prebiotic synthesis of uracil and its derivatives starting from HCN as the only carbon source."}
{"id": "PMID:208153", "title": "Retrograde amnesia produced by several treatments: evidence for a common neurobiological mechanism.", "content": "This experiment examined the effects on memory of various amnestic treatments in animals earlier treated with the alpha-adrenergic antagonist phenoxybenzamine (PBZ). Thirty minutes before being trained in a one-trial inhibitory (passive) avoidance task, animals received an injection of PBZ or saline. Immediately after training, each animal received one of the following amnestic treatments: stimulation of the frontal cortex or amygdala, pentylenetetrazol, diethyldithiocarbamate, or cycloheximide. In control animals, each treatment produced retrograde amnesia. However, PBZ-treated animals did not develop amnesia. These findings suggest that there may be a common neurobiological mechanism underlying the amnesias produced by many treatments.", "contents": "Retrograde amnesia produced by several treatments: evidence for a common neurobiological mechanism. This experiment examined the effects on memory of various amnestic treatments in animals earlier treated with the alpha-adrenergic antagonist phenoxybenzamine (PBZ). Thirty minutes before being trained in a one-trial inhibitory (passive) avoidance task, animals received an injection of PBZ or saline. Immediately after training, each animal received one of the following amnestic treatments: stimulation of the frontal cortex or amygdala, pentylenetetrazol, diethyldithiocarbamate, or cycloheximide. In control animals, each treatment produced retrograde amnesia. However, PBZ-treated animals did not develop amnesia. These findings suggest that there may be a common neurobiological mechanism underlying the amnesias produced by many treatments."}
{"id": "PMID:208154", "title": "Prostaglandin restoration of the interferon response of hyporeactive animals.", "content": "Virus-infected animals and those bearing various types of malignancies progressively lose the ability to respond to interferon inducers. The interferon response of virus-infected animals could be restored to normal levels when inducers were administered with certain prostaglandins. This suggests that prostaglandins may enhance the therapeutic efficacy of interferon inducers as antiviral and antineoplastic agents.", "contents": "Prostaglandin restoration of the interferon response of hyporeactive animals. Virus-infected animals and those bearing various types of malignancies progressively lose the ability to respond to interferon inducers. The interferon response of virus-infected animals could be restored to normal levels when inducers were administered with certain prostaglandins. This suggests that prostaglandins may enhance the therapeutic efficacy of interferon inducers as antiviral and antineoplastic agents."}
{"id": "PMID:208155", "title": "Higher order structure of simian virus 40 chromatin.", "content": "Simian virus 40 nucleoprotein complexes undergo an ionic strength-dependent structural transition. At moderate ionic strength they contain histone H1 as well as the nucleosomal histones and have a compact conformation with globular subunits 190 angstroms in diameter. At high ionic strength histone H1 is released, and the structure unfolds into chains with an average of 24 nucleosomes. The extended viral chromatin converts to the compact form by the addition of histone H1. Transcriptionally active simian virus 40 chromatin undergoes the same structural transitions. The higher order structure of viral chromatin may be analogous to the compact state of cellular chromatin fibers observed at physiological ionic strength.", "contents": "Higher order structure of simian virus 40 chromatin. Simian virus 40 nucleoprotein complexes undergo an ionic strength-dependent structural transition. At moderate ionic strength they contain histone H1 as well as the nucleosomal histones and have a compact conformation with globular subunits 190 angstroms in diameter. At high ionic strength histone H1 is released, and the structure unfolds into chains with an average of 24 nucleosomes. The extended viral chromatin converts to the compact form by the addition of histone H1. Transcriptionally active simian virus 40 chromatin undergoes the same structural transitions. The higher order structure of viral chromatin may be analogous to the compact state of cellular chromatin fibers observed at physiological ionic strength."}
{"id": "PMID:208156", "title": "Virus-induced diabetes mellitus: reovirus infection of pancreatic beta cells in mice.", "content": "Reovirus type 3, passaged in pancreatic beta-cell cultures, produced an insulitis when inoculated into 1- to 2-week-old mice. By means of a double-label antibody technique, in which we used fluorescein-labeled antibody to reovirus and rhodamine-labeled antibody to insulin, reovirus antigens were found in beta cells. By electron microscopy, viral particles in different stages of morphogenesis were observed in insulin-containing beta cells but not glucagon-containing alpha cells. The infection resulted in destruction of beta cells, reduction in the insulin content of the pancreas, and alteration in the host's capacity to respond normally to a glucose tolerance test.", "contents": "Virus-induced diabetes mellitus: reovirus infection of pancreatic beta cells in mice. Reovirus type 3, passaged in pancreatic beta-cell cultures, produced an insulitis when inoculated into 1- to 2-week-old mice. By means of a double-label antibody technique, in which we used fluorescein-labeled antibody to reovirus and rhodamine-labeled antibody to insulin, reovirus antigens were found in beta cells. By electron microscopy, viral particles in different stages of morphogenesis were observed in insulin-containing beta cells but not glucagon-containing alpha cells. The infection resulted in destruction of beta cells, reduction in the insulin content of the pancreas, and alteration in the host's capacity to respond normally to a glucose tolerance test."}
{"id": "PMID:208158", "title": "[Thrombocytosis and cancer. Apropos of a chronological series of 100 patients].", "content": "The authors report a personal chronological series of 100 cancer patients submitted to an analytical study, and noted thrombocytosis in 18% of cases. They attempt to draw up a correlation between the presence of increased platelets, and the site of the primary tumour, its spread, the state of anemia or iron deficiency in these patients. During a general review of the literature, they compare their results with those of various american and german series and report the various pathogenic hypotheses suggested upto date. They emphasise the fact that routine platelet counts may be of great interest in the detection of certain early carcinomas in spite of the generally moderate levels of thrombocytosis observed. They therefore have a place in routine health checks.", "contents": "[Thrombocytosis and cancer. Apropos of a chronological series of 100 patients]. The authors report a personal chronological series of 100 cancer patients submitted to an analytical study, and noted thrombocytosis in 18% of cases. They attempt to draw up a correlation between the presence of increased platelets, and the site of the primary tumour, its spread, the state of anemia or iron deficiency in these patients. During a general review of the literature, they compare their results with those of various american and german series and report the various pathogenic hypotheses suggested upto date. They emphasise the fact that routine platelet counts may be of great interest in the detection of certain early carcinomas in spite of the generally moderate levels of thrombocytosis observed. They therefore have a place in routine health checks."}
{"id": "PMID:208159", "title": "[Primary \"muscle\" tumors or tumors with a myosarcomatous component of the central nervous system. General review and attempt at classification based on 2 anatomo-clinical observations].", "content": "The authors report the first two French cases of primary rabdomyosarcoma of the central nervous system. They then review the literature on muscle tumours or primary myosarcomas of the nervous system of which 29 cases have now been published. From the point of view of morphology and classification, one should distinguish firstly, purely mesenchymatous tumours (rhabdomyosarcomas, leiosarcoma, mesenchymoma) and secondly, composite tumours of connective tissue or spino-epithelial tumours (medullomyoblastomas, neuromyoblastomas, gliomyosarcomas). Their histogenesis occurs from the ectomesenchyme of the neural crests.", "contents": "[Primary \"muscle\" tumors or tumors with a myosarcomatous component of the central nervous system. General review and attempt at classification based on 2 anatomo-clinical observations]. The authors report the first two French cases of primary rabdomyosarcoma of the central nervous system. They then review the literature on muscle tumours or primary myosarcomas of the nervous system of which 29 cases have now been published. From the point of view of morphology and classification, one should distinguish firstly, purely mesenchymatous tumours (rhabdomyosarcomas, leiosarcoma, mesenchymoma) and secondly, composite tumours of connective tissue or spino-epithelial tumours (medullomyoblastomas, neuromyoblastomas, gliomyosarcomas). Their histogenesis occurs from the ectomesenchyme of the neural crests."}
{"id": "PMID:208160", "title": "[Post-meningococcal rheumatism].", "content": "Two cases of post-meningococcal inflammatory arthritis with a relapsing course in one case are reported. The authors then recall the characteristics of the joint manifestations during meningococcal infections in the light of other cases in the literature. These arthropathies are generally aseptic and their resistance to antibiotics is remarkable, whilst non- steroid anti-inflammatory drugs, even used alone as in one of the cases reported here, are remarkably effective. The pathogenesis of these cases of arthritis is not clear: it seems however according to Greenwood and Whittle that they are manifestations of immuno-allergic type. This \"post-meningococcal rheumatism\" may be compared to the gonococcal rheumatism of certain cases of Reiter's syndrome.", "contents": "[Post-meningococcal rheumatism]. Two cases of post-meningococcal inflammatory arthritis with a relapsing course in one case are reported. The authors then recall the characteristics of the joint manifestations during meningococcal infections in the light of other cases in the literature. These arthropathies are generally aseptic and their resistance to antibiotics is remarkable, whilst non- steroid anti-inflammatory drugs, even used alone as in one of the cases reported here, are remarkably effective. The pathogenesis of these cases of arthritis is not clear: it seems however according to Greenwood and Whittle that they are manifestations of immuno-allergic type. This \"post-meningococcal rheumatism\" may be compared to the gonococcal rheumatism of certain cases of Reiter's syndrome."}
{"id": "PMID:208161", "title": "[Rupture of the rotator tendon].", "content": "The authors report 25 cases of rupture of the rotator tendons operated on at the Stephanie Hospital in Strasburg, and discuss the surgical indications. Debeyre's technic was used with satisfactory overall results both on pain and function.", "contents": "[Rupture of the rotator tendon]. The authors report 25 cases of rupture of the rotator tendons operated on at the Stephanie Hospital in Strasburg, and discuss the surgical indications. Debeyre's technic was used with satisfactory overall results both on pain and function."}
{"id": "PMID:208181", "title": "Rupture of a parasellar aneurysm with a coexisting pituitary tumor.", "content": "The unusual occurrence of a pituitary tumor and a parasellar aneurysm is reported. The aneurysm ruptured and mimicked spontaneous infarction of the pituitary tumor. The importance of performing cerebral angiography before emergency surgical decompression of a presumed pituitary tumor infarction is emphasized.", "contents": "Rupture of a parasellar aneurysm with a coexisting pituitary tumor. The unusual occurrence of a pituitary tumor and a parasellar aneurysm is reported. The aneurysm ruptured and mimicked spontaneous infarction of the pituitary tumor. The importance of performing cerebral angiography before emergency surgical decompression of a presumed pituitary tumor infarction is emphasized."}
{"id": "PMID:208182", "title": "Adenoid cystic carcinoma of the breast.", "content": "We have presented a case of adenoid cystic carcinoma of the breast and reviewed the literature, with emphasis on the behavior of this rare neoplasm and the fact that its prognosis appears to be more favorable than that of other more common histologic types of breast cancer. The accumulated information about adenoid cystic carcinoma of the breast that exists to date is insufficient to allow dogmatic statements, but one can conclude that total mastectomy seems to be the treatment of choice in selected cases.", "contents": "Adenoid cystic carcinoma of the breast. We have presented a case of adenoid cystic carcinoma of the breast and reviewed the literature, with emphasis on the behavior of this rare neoplasm and the fact that its prognosis appears to be more favorable than that of other more common histologic types of breast cancer. The accumulated information about adenoid cystic carcinoma of the breast that exists to date is insufficient to allow dogmatic statements, but one can conclude that total mastectomy seems to be the treatment of choice in selected cases."}
{"id": "PMID:208183", "title": "Granular cell tumor of the abdominal wall musculature.", "content": "Granular cell tumor (myoblastoma) is a relatively frequent neoplasm found in many different anatomic locations. This is a case of such a tumor arising in the abdominal wall musculature, an extremely unusual site of occurrence. Excision with generous margins is required to prevent recurrence.", "contents": "Granular cell tumor of the abdominal wall musculature. Granular cell tumor (myoblastoma) is a relatively frequent neoplasm found in many different anatomic locations. This is a case of such a tumor arising in the abdominal wall musculature, an extremely unusual site of occurrence. Excision with generous margins is required to prevent recurrence."}
{"id": "PMID:208184", "title": "Biomedical survey in Irian Jaya (West Irian), Indonesia.", "content": "A biomedical survey was conducted in several areas of Irian Jaya, Indonesia in July 1972 in association with an investigation of reports of a cholera outbreak. Stool specimens, blood smears and sera were collected and examined for evidence of parasitic as well as other infectious diseases. A total of 114 stools were examined and the most commonly found intestinal parasites were Trichuris trichiura (94%), Ascaris lumbricoides (74%), hookworm (58%), Entamoeba coli (15%), Endolimax nana (8%), Entamoeba histolytica (7), Entamoeba hartmanni (4%), Giardia lamblia (3%) and Chilomastix mesnili (3%). A total of 513 blood smears were examined and Wucheria bancrofti microfilariae were detected in 4% and malaria in 4% (Plasmodium falciparum 3%, Plasmodium vivax 2%). The malaria and filarial positive individuals lived in Beeuw, Waigeo and Arar, Sorong. These parasitic infections were not detected in people from Biak City and Sburia, Biak. Sera were collected from 357 persons and significant antibody titers were found for Entamoeba histolytica (4%) Toxoplasma gondii (7%), Influenza A2 Hong Kong 68 (65%), Influenza B Taiwan 68 (78%), Japanese encephalitis virus (87%) and Dengue 1 virus (79%).", "contents": "Biomedical survey in Irian Jaya (West Irian), Indonesia. A biomedical survey was conducted in several areas of Irian Jaya, Indonesia in July 1972 in association with an investigation of reports of a cholera outbreak. Stool specimens, blood smears and sera were collected and examined for evidence of parasitic as well as other infectious diseases. A total of 114 stools were examined and the most commonly found intestinal parasites were Trichuris trichiura (94%), Ascaris lumbricoides (74%), hookworm (58%), Entamoeba coli (15%), Endolimax nana (8%), Entamoeba histolytica (7), Entamoeba hartmanni (4%), Giardia lamblia (3%) and Chilomastix mesnili (3%). A total of 513 blood smears were examined and Wucheria bancrofti microfilariae were detected in 4% and malaria in 4% (Plasmodium falciparum 3%, Plasmodium vivax 2%). The malaria and filarial positive individuals lived in Beeuw, Waigeo and Arar, Sorong. These parasitic infections were not detected in people from Biak City and Sburia, Biak. Sera were collected from 357 persons and significant antibody titers were found for Entamoeba histolytica (4%) Toxoplasma gondii (7%), Influenza A2 Hong Kong 68 (65%), Influenza B Taiwan 68 (78%), Japanese encephalitis virus (87%) and Dengue 1 virus (79%)."}
{"id": "PMID:208186", "title": "A mammalian cell mutant with temperature-sensitive thymidine kinase.", "content": "We have isolated a mutant clone from mouse FM3A cells with temperature-sensitive defects both in cytokinesis and in thymidine kinase enzyme activity. The clone, designated tsCl.B59, was isolated after mutagenesis at 33 degrees C followed by exposure to cytosine arabinoside at 39 degrees C. It was derived from a thymidine kinase deficient, 5-bromodeoxyuridine-resistant clone (S-BUCl.42) which was originally derived from wild-type clone H-5 of FM3A cells. The temperature-sensitive mutant clone grows normally at 33 degrees C, but not at 39 degrees C, where it exhibits an increased frequency of multinucleate cells due to defective cytokinesis. Unlike the parental S-BUCl.42 cells, which have negligible thymidine kinase activity and are unable to incorporate 3H-thymidine, the mutant in corporates substantial amounts of 3H-thymidine at 33 degrees C, although its thymidine kinase activity remains lower than that of wild-type H-5 cells. When cultures of tsCl.B59 cells are transferred to 39 degrees C, incorporation of 3H-thymidine decreases markedly. The decrease has been shown to be due to thermolability of the thymidine kinase in tsCl.B59 cells.", "contents": "A mammalian cell mutant with temperature-sensitive thymidine kinase. We have isolated a mutant clone from mouse FM3A cells with temperature-sensitive defects both in cytokinesis and in thymidine kinase enzyme activity. The clone, designated tsCl.B59, was isolated after mutagenesis at 33 degrees C followed by exposure to cytosine arabinoside at 39 degrees C. It was derived from a thymidine kinase deficient, 5-bromodeoxyuridine-resistant clone (S-BUCl.42) which was originally derived from wild-type clone H-5 of FM3A cells. The temperature-sensitive mutant clone grows normally at 33 degrees C, but not at 39 degrees C, where it exhibits an increased frequency of multinucleate cells due to defective cytokinesis. Unlike the parental S-BUCl.42 cells, which have negligible thymidine kinase activity and are unable to incorporate 3H-thymidine, the mutant in corporates substantial amounts of 3H-thymidine at 33 degrees C, although its thymidine kinase activity remains lower than that of wild-type H-5 cells. When cultures of tsCl.B59 cells are transferred to 39 degrees C, incorporation of 3H-thymidine decreases markedly. The decrease has been shown to be due to thermolability of the thymidine kinase in tsCl.B59 cells."}
{"id": "PMID:208188", "title": "Tumor imaging with x-rays using macrophage uptake of radiopaque fluorocarbon emulsions.", "content": "Radiopaque fluorocarbon (RFC) emulsions were prepared with small particle size and high concentration of the fluorocarbon. When RFC emulsions were injected intravenously in hamsters, rats, and mice with eight types of malignant tumors, the tumors became radiopaque, except in the mice with spontaneous teratoma of the ovaries. Tumors as small as 3 to 4 mm could be defined radiographically using routine x-ray techniques. The tumors remained radiopaque for days to weeks after injection. Light and electron microscopy revealed characteristic fluorocarbon vacuoles primarily in the tumor macrophages. Thus RFC emulsions may be useful in detection of malignant tumors.", "contents": "Tumor imaging with x-rays using macrophage uptake of radiopaque fluorocarbon emulsions. Radiopaque fluorocarbon (RFC) emulsions were prepared with small particle size and high concentration of the fluorocarbon. When RFC emulsions were injected intravenously in hamsters, rats, and mice with eight types of malignant tumors, the tumors became radiopaque, except in the mice with spontaneous teratoma of the ovaries. Tumors as small as 3 to 4 mm could be defined radiographically using routine x-ray techniques. The tumors remained radiopaque for days to weeks after injection. Light and electron microscopy revealed characteristic fluorocarbon vacuoles primarily in the tumor macrophages. Thus RFC emulsions may be useful in detection of malignant tumors."}
{"id": "PMID:208197", "title": "Thermal transformation of cholecalciferol between 100--170 degrees C.", "content": "Cholecalciferol is transformed, irreversibly, to pyrocholecalciferol and isopyrocholecalciferol. The rate constant, as a function of temperature, for this transformation from the equilibrium mixture of cholecalciferol and precholecalciferol has been determined for temperatures between 100--170 degrees C and is slower than the precholecalciferol-cholecalciferol interconversion. The ratio of rates of production of pyro to isopyro derivatives is 2:1 throughout.", "contents": "Thermal transformation of cholecalciferol between 100--170 degrees C. Cholecalciferol is transformed, irreversibly, to pyrocholecalciferol and isopyrocholecalciferol. The rate constant, as a function of temperature, for this transformation from the equilibrium mixture of cholecalciferol and precholecalciferol has been determined for temperatures between 100--170 degrees C and is slower than the precholecalciferol-cholecalciferol interconversion. The ratio of rates of production of pyro to isopyro derivatives is 2:1 throughout."}
{"id": "PMID:208198", "title": "Further characterization of the effects of hypophysectomy, FSH and estrogen on LH stimulation of testosterone production in Leydig cells isolated from immature rats.", "content": "Hypophysectomy of immature rats results after 5 days in a loss of LH responsiveness of Leydig cells. LH responsiveness can be partly maintained by treatment with FSH for 5 days. When estradiol benzoate was administered together with FSH to hypophysectomized rats the maintenance of LH responsiveness was not observed. The loss in LH responsiveness after hypophysectomy in terms of testosterone production could not be explained by either a change in the amount of Leydig cells present in the Leydig cell preparation or to a higher conversion of testosterone. The LH-stimulated cAMP production in cells from hypophysectomized rats was very low compared to cells from intact rats. There was no difference between cAMP production of Leydig cells from untreated, FSH-treated or FSH plus estradiol benzoate treated hypophysectomized rats. During the first 2 days after hypophysectomy LH responsiveness in both untreated and FSH-treated rats showed a comparable decrease. From day 2 after hypophysectomy LH responsiveness remained at a constant level in cells from rats treated with FSH, but declined further in cells from untreated rats. A single injection of estradiol benzoate to hypophysectomized rats treated with FSH counteracted the effect of FSH on LH responsiveness, but only when estradiol was administered at that time after hypophysectomy, when the effect of FSH on LH responsiveness was clear.", "contents": "Further characterization of the effects of hypophysectomy, FSH and estrogen on LH stimulation of testosterone production in Leydig cells isolated from immature rats. Hypophysectomy of immature rats results after 5 days in a loss of LH responsiveness of Leydig cells. LH responsiveness can be partly maintained by treatment with FSH for 5 days. When estradiol benzoate was administered together with FSH to hypophysectomized rats the maintenance of LH responsiveness was not observed. The loss in LH responsiveness after hypophysectomy in terms of testosterone production could not be explained by either a change in the amount of Leydig cells present in the Leydig cell preparation or to a higher conversion of testosterone. The LH-stimulated cAMP production in cells from hypophysectomized rats was very low compared to cells from intact rats. There was no difference between cAMP production of Leydig cells from untreated, FSH-treated or FSH plus estradiol benzoate treated hypophysectomized rats. During the first 2 days after hypophysectomy LH responsiveness in both untreated and FSH-treated rats showed a comparable decrease. From day 2 after hypophysectomy LH responsiveness remained at a constant level in cells from rats treated with FSH, but declined further in cells from untreated rats. A single injection of estradiol benzoate to hypophysectomized rats treated with FSH counteracted the effect of FSH on LH responsiveness, but only when estradiol was administered at that time after hypophysectomy, when the effect of FSH on LH responsiveness was clear."}
{"id": "PMID:208199", "title": "Direct radioimmunoassay of specific urinary estrogen glucosiduronates in normal men and nonpregnant women.", "content": "Direct radioimmunoassay are described for the measurement of each of three specific estrogen glucosiduronates: estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate and estriol-16 alpha-glucosiduronate in urine. Each assay utilizes a specific antiserum prepared by complexing the carboxylic acid group of the appropriate glucosiduronate to the epsilon-amino group of lysine in bovine serum albumin or bovine thyroglobulin. The antisera showed little or no cross reactivity toward other estrogens that might be present in significant amounts in urine. These antisera were used for the direct assay of the conjugates in urine from normal men and nonpregnant women without prior extraction or chromatography. The values were similar to those obtained after extraction, chromatographic purification on DEAE-Sephadex and subsequent immunoassay; The following mean values +/- SE (microgram/g creatinine) were obtained: estrone glucosiduronate, male 10.1 +/- 0.6, follicular phase female 17.3+/- 1.6, luteal phase female 31.8 +/- 2.5; 17 beta-estradiol-17-glucosiduronate, male 1.7 +/- 0.3, follicular phase female 2.4 +/- 0.1, luteal phase female 4.2 +/- 0.4; estriol-16 alpha-glucosiduronate, male 1.8 +/- 0.2, follicular phase female 4.7 +/- 0.9, luteal phase female 10.0 +/- 1.6.", "contents": "Direct radioimmunoassay of specific urinary estrogen glucosiduronates in normal men and nonpregnant women. Direct radioimmunoassay are described for the measurement of each of three specific estrogen glucosiduronates: estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate and estriol-16 alpha-glucosiduronate in urine. Each assay utilizes a specific antiserum prepared by complexing the carboxylic acid group of the appropriate glucosiduronate to the epsilon-amino group of lysine in bovine serum albumin or bovine thyroglobulin. The antisera showed little or no cross reactivity toward other estrogens that might be present in significant amounts in urine. These antisera were used for the direct assay of the conjugates in urine from normal men and nonpregnant women without prior extraction or chromatography. The values were similar to those obtained after extraction, chromatographic purification on DEAE-Sephadex and subsequent immunoassay; The following mean values +/- SE (microgram/g creatinine) were obtained: estrone glucosiduronate, male 10.1 +/- 0.6, follicular phase female 17.3+/- 1.6, luteal phase female 31.8 +/- 2.5; 17 beta-estradiol-17-glucosiduronate, male 1.7 +/- 0.3, follicular phase female 2.4 +/- 0.1, luteal phase female 4.2 +/- 0.4; estriol-16 alpha-glucosiduronate, male 1.8 +/- 0.2, follicular phase female 4.7 +/- 0.9, luteal phase female 10.0 +/- 1.6."}
{"id": "PMID:208200", "title": "Steroidogenic activity of hACTH and related peptides on the human neocortex and fetal adrenal cortex in organ culture.", "content": "Explants prepared from the neocortex and the fetal zone of the human fetal adrenal (gestational age 13 to 18weeks) were maintained under conditions of organ culture for 7 to 9 days during which time they were exposed to hACTH and various related peptides. Corticotrophic activity was monitored by the daily release of dehydroepiandrosterone sulfate (3beta-hydroxy-5-androsten-17-one, 3-sulfate; DHA-S) and cortisol as quantified by radioimmunoassay, hACTH (2.2 x 10(-9) - 2.2 x 10(-8)M) was the most active in sustaining steroidogenesis by both neocortical and fetocortical cells. alpha-MSH possessed similar properties but not at concentrations lower than 10(-6)M, whereas CLIP (4.4 x 10(-9) - 1.1 x 10(-7)M), the 18-39 C-terminal moiety of ACTH, was devoid of activity. Corticotrophic activity with respect to fetocortical explants appeared to be that of maintenance of function best illustrated by dehydroepiandrosterone sulfate biosynthesis, while enhancement of steroidogenesis was observed in the neocortex as manifested by cortisol release. Although not eliminating the possible existence of a specific fetal corticotrophin related to ACTH1-39, the data indicate that hACTH is capable of regulating steroidogenesis in the fetal zone which is primarily geared to the formation of dehydroepiandrosterone sulfate.", "contents": "Steroidogenic activity of hACTH and related peptides on the human neocortex and fetal adrenal cortex in organ culture. Explants prepared from the neocortex and the fetal zone of the human fetal adrenal (gestational age 13 to 18weeks) were maintained under conditions of organ culture for 7 to 9 days during which time they were exposed to hACTH and various related peptides. Corticotrophic activity was monitored by the daily release of dehydroepiandrosterone sulfate (3beta-hydroxy-5-androsten-17-one, 3-sulfate; DHA-S) and cortisol as quantified by radioimmunoassay, hACTH (2.2 x 10(-9) - 2.2 x 10(-8)M) was the most active in sustaining steroidogenesis by both neocortical and fetocortical cells. alpha-MSH possessed similar properties but not at concentrations lower than 10(-6)M, whereas CLIP (4.4 x 10(-9) - 1.1 x 10(-7)M), the 18-39 C-terminal moiety of ACTH, was devoid of activity. Corticotrophic activity with respect to fetocortical explants appeared to be that of maintenance of function best illustrated by dehydroepiandrosterone sulfate biosynthesis, while enhancement of steroidogenesis was observed in the neocortex as manifested by cortisol release. Although not eliminating the possible existence of a specific fetal corticotrophin related to ACTH1-39, the data indicate that hACTH is capable of regulating steroidogenesis in the fetal zone which is primarily geared to the formation of dehydroepiandrosterone sulfate."}
{"id": "PMID:208201", "title": "Separation of estrogen conjugates by high pressure liquid chromatography.", "content": "High pressure liquid chromatography using a prepacked commercial strong anion exchanger column (mu Partisil 10 SAX, 25 cm x 4.6 mm) was used to separate a mixture of eight estrogen conjugates. Chromatographic conditions using a 0.01 M potassium phosphate or 0.1 M NaCl as solvent in the isocratic mode are described for the separation of estrone glucosiduronate, 17beta-estradiol-3-glucosiduronate, 17beta-estradiol-17-glucosiduronate, estriol-3-glucosiduronate, estriol-16alpha-glucosiduronate, estriol-17-glucosiduronate, estrone sulfate and 17beta-estradiol-3-sulfate. This system gives high resolution of the estrogen conjugates in small eluent volumes in less than 30 min. The advantages of this high pressure liquid chromatographic system over other methods of separation are discussed.", "contents": "Separation of estrogen conjugates by high pressure liquid chromatography. High pressure liquid chromatography using a prepacked commercial strong anion exchanger column (mu Partisil 10 SAX, 25 cm x 4.6 mm) was used to separate a mixture of eight estrogen conjugates. Chromatographic conditions using a 0.01 M potassium phosphate or 0.1 M NaCl as solvent in the isocratic mode are described for the separation of estrone glucosiduronate, 17beta-estradiol-3-glucosiduronate, 17beta-estradiol-17-glucosiduronate, estriol-3-glucosiduronate, estriol-16alpha-glucosiduronate, estriol-17-glucosiduronate, estrone sulfate and 17beta-estradiol-3-sulfate. This system gives high resolution of the estrogen conjugates in small eluent volumes in less than 30 min. The advantages of this high pressure liquid chromatographic system over other methods of separation are discussed."}
{"id": "PMID:208202", "title": "Serological evidence of the occurrence of bluetongue in Iraq.", "content": "Precipitating antibodies against bluetongue were detected in sheep and goat serum samples collected from animals slaughtered in Baghdad abattoir. Out of 294 sheep serum samples and 110 goat serum samples examined, 28 and 18 samples respectively showed precipitating activity. In addition, examination of sheep serum samples collected from localities where clinical cases similar to bluetongue were previously reported revealed the presence of bluetongue precipitating antibodies in 101 sera out of 198 samples examined. This is the first report confirming the occurrence of bluetongue in Iraq.", "contents": "Serological evidence of the occurrence of bluetongue in Iraq. Precipitating antibodies against bluetongue were detected in sheep and goat serum samples collected from animals slaughtered in Baghdad abattoir. Out of 294 sheep serum samples and 110 goat serum samples examined, 28 and 18 samples respectively showed precipitating activity. In addition, examination of sheep serum samples collected from localities where clinical cases similar to bluetongue were previously reported revealed the presence of bluetongue precipitating antibodies in 101 sera out of 198 samples examined. This is the first report confirming the occurrence of bluetongue in Iraq."}
{"id": "PMID:208203", "title": "[Inhibition of alkaline phosphatase I of Pichia guilliermondii yeast in vitro and in vivo].", "content": "The rate of p-nitrophenyl phosphate and flavin mononucleotide (FMN) hydrolysis by the partially purified preparation of alkaline phosphatase I of Pichia guilliermondii flavinogenic yeast was studied as affected by different substrates and inorganic ions. Their Km was established to be 2.0 X 10(-4) m and 2.5 X 10(-4) M, respectively. Dephosphorylation of p-nitrophenylphosphate and FMN was inhibited competitively by beta-glycerophosphate (Ki = 3.1 X 10(-3) M, respectively). The presence of inorganic phosphate ions in the reaction mixture decreases or removes inhibition of these compounds hydrolysis by other substrates of alkaline phosphatase I. The activity of alkaline phosphatase I increases in the presence of Mg2+ and was strongly inhibited in the presence of Be2+, Cu2+, Zn2+, Cd2+ and inorganic phosphate, the mixture of Be2+ and F- being the most effective. This mixture inhibited the phosphatase activity of the partially purified preparation of alkaline phosphatase I of the cell-free extract as well as of intact cells in both the alkaline and acid zones of pH (8.6 and 5.5, respectively). Incubation of the washed iron-deficient P. guilliermondii cells in the presence of Be2+ and F- did not result in accumulation of FMN in the yeast culture. A possible role of nonspecific phosphomonoesterases in hydrolysis of FMN in vivo is discussed.", "contents": "[Inhibition of alkaline phosphatase I of Pichia guilliermondii yeast in vitro and in vivo]. The rate of p-nitrophenyl phosphate and flavin mononucleotide (FMN) hydrolysis by the partially purified preparation of alkaline phosphatase I of Pichia guilliermondii flavinogenic yeast was studied as affected by different substrates and inorganic ions. Their Km was established to be 2.0 X 10(-4) m and 2.5 X 10(-4) M, respectively. Dephosphorylation of p-nitrophenylphosphate and FMN was inhibited competitively by beta-glycerophosphate (Ki = 3.1 X 10(-3) M, respectively). The presence of inorganic phosphate ions in the reaction mixture decreases or removes inhibition of these compounds hydrolysis by other substrates of alkaline phosphatase I. The activity of alkaline phosphatase I increases in the presence of Mg2+ and was strongly inhibited in the presence of Be2+, Cu2+, Zn2+, Cd2+ and inorganic phosphate, the mixture of Be2+ and F- being the most effective. This mixture inhibited the phosphatase activity of the partially purified preparation of alkaline phosphatase I of the cell-free extract as well as of intact cells in both the alkaline and acid zones of pH (8.6 and 5.5, respectively). Incubation of the washed iron-deficient P. guilliermondii cells in the presence of Be2+ and F- did not result in accumulation of FMN in the yeast culture. A possible role of nonspecific phosphomonoesterases in hydrolysis of FMN in vivo is discussed."}
{"id": "PMID:208204", "title": "[The content of thiamine, its coenzyme form and activity of thiamine diphosphate-dependent enzymes in ontogenesis].", "content": "In experiments on rats of different age it is shown that the lowest content of thiamine and its phosphoric ethers in the liver is typical of the early periods of embryonal development and the highest one of the first days after birth. A direct dependence is established between the content of thiamine, its coenzyme form, enzyme of thiamine diphosphate synthesis (thiamine pyrophosphokinase) and thiamine diphosphate-containing enzyme (transketolase) in the rat liver in different periods of ontogenesis.", "contents": "[The content of thiamine, its coenzyme form and activity of thiamine diphosphate-dependent enzymes in ontogenesis]. In experiments on rats of different age it is shown that the lowest content of thiamine and its phosphoric ethers in the liver is typical of the early periods of embryonal development and the highest one of the first days after birth. A direct dependence is established between the content of thiamine, its coenzyme form, enzyme of thiamine diphosphate synthesis (thiamine pyrophosphokinase) and thiamine diphosphate-containing enzyme (transketolase) in the rat liver in different periods of ontogenesis."}
{"id": "PMID:208205", "title": "[Effect of ions on determination of 3',5'-AMP by the method of saturation].", "content": "The effects of La2+, Pb2+, Ba2+, Zn2+, Ca2+, Mg2+, Mn2+, NH+4 in concentrations of 10(-7), 10(-5), 10(-3) M were studied as applied to the protein binding of cyclic 3' : 5' = AMP. It is shown that Ba2+, La2+, Pb2+ increase the binding, while Zn2+ has no effect, and Mn2+, NH+4 decrease the binding of 3' : 5' = AMP. The effects of Ca2+ and Cd2+ were dependent on the concentration. The maximal binding in the presence of Ca2+ and Cd2+ was observed at a concentration of 10(-5) M and 10(-3) M, respectively. It is suggested that Mg2+ and Ca2+ take part in the regulation of cyclic AMP binding with proteinkinase in vivo.", "contents": "[Effect of ions on determination of 3',5'-AMP by the method of saturation]. The effects of La2+, Pb2+, Ba2+, Zn2+, Ca2+, Mg2+, Mn2+, NH+4 in concentrations of 10(-7), 10(-5), 10(-3) M were studied as applied to the protein binding of cyclic 3' : 5' = AMP. It is shown that Ba2+, La2+, Pb2+ increase the binding, while Zn2+ has no effect, and Mn2+, NH+4 decrease the binding of 3' : 5' = AMP. The effects of Ca2+ and Cd2+ were dependent on the concentration. The maximal binding in the presence of Ca2+ and Cd2+ was observed at a concentration of 10(-5) M and 10(-3) M, respectively. It is suggested that Mg2+ and Ca2+ take part in the regulation of cyclic AMP binding with proteinkinase in vivo."}
{"id": "PMID:208206", "title": "[Adenosine triphosphatase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activity of pancreas of thyroidectomized rats].", "content": "Activity of enzymes catalizing bioenergetic processes of substance transport through cell membranes, adenosine triphosphatase and para-nitrophenyl phosphates, activity of certain enzymes of carbohydrate metabolism, lactate dehydrogenase and glucose-6-phosphate dehydrogenase, as well as to 5'-nucleotidase taking part in nucleic metabolism were determined in the pancreas of thyreoidectomized rats. Simultaneously the content of lactic acid, phosphorus, potassium and sodium, which immediately related to activation of the mentioned enzymes, was determined in the pancreas. In thyroidectomized rats the activity of Mg2+, Na+, K+-ATPase, Na+, K+-ATPase and lactate dehydrogenase in the pancreas increases, that of glucose-6-phosphate dehydrogenase, para-nitrophenylphosphatase and 5-nucleotidase decreases, the content of lactic acid, potassium, sodium and phosphorus increases.", "contents": "[Adenosine triphosphatase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activity of pancreas of thyroidectomized rats]. Activity of enzymes catalizing bioenergetic processes of substance transport through cell membranes, adenosine triphosphatase and para-nitrophenyl phosphates, activity of certain enzymes of carbohydrate metabolism, lactate dehydrogenase and glucose-6-phosphate dehydrogenase, as well as to 5'-nucleotidase taking part in nucleic metabolism were determined in the pancreas of thyreoidectomized rats. Simultaneously the content of lactic acid, phosphorus, potassium and sodium, which immediately related to activation of the mentioned enzymes, was determined in the pancreas. In thyroidectomized rats the activity of Mg2+, Na+, K+-ATPase, Na+, K+-ATPase and lactate dehydrogenase in the pancreas increases, that of glucose-6-phosphate dehydrogenase, para-nitrophenylphosphatase and 5-nucleotidase decreases, the content of lactic acid, potassium, sodium and phosphorus increases."}
{"id": "PMID:208211", "title": "Fluorometric microassays of adenylate kinase, an enzyme important in energy metabolism.", "content": "The adenylate kinase system offers a mechanism for the rapid provision of energy by catalysing the production of ATP from ADP. Fluormetric micromethods were developed for determination of the activity of this enzyme using either formation of ADP or ATP, in each case measured by coupling to suitable dehydrogenase reactions. Both procedures yielded results in good agreement, but when ADP formation was measured an interfering phosphatase splitting of ATP had to be corrected for. Therefore, ADP was preferred as the substrate and its conversion to ATP was determined in a coupled hexokinase-glucose-6-phosphate dehydrogenase reaction yielding stoichiometric amounts of NADPH which were measured by the native fluorescence of this form of the nucleotide. The sensitivity and reproducibility of our micro-method permitted assay of small samples (50-500 ng) such as a layer of cerebellar cortical nerve cells and of insulin producing cells from the islets of Langerhans. Although not reaching the high values in muscle, these cells showed significantly higher activities than parenchymatous cells from the liver and the exocrine pancreas. The sensitivity attained is more than required for assay of clinical fine needle biopsies and is quite satisfactory for detection and estimation of adenylate kinase contaminants in enzyme preparations.", "contents": "Fluorometric microassays of adenylate kinase, an enzyme important in energy metabolism. The adenylate kinase system offers a mechanism for the rapid provision of energy by catalysing the production of ATP from ADP. Fluormetric micromethods were developed for determination of the activity of this enzyme using either formation of ADP or ATP, in each case measured by coupling to suitable dehydrogenase reactions. Both procedures yielded results in good agreement, but when ADP formation was measured an interfering phosphatase splitting of ATP had to be corrected for. Therefore, ADP was preferred as the substrate and its conversion to ATP was determined in a coupled hexokinase-glucose-6-phosphate dehydrogenase reaction yielding stoichiometric amounts of NADPH which were measured by the native fluorescence of this form of the nucleotide. The sensitivity and reproducibility of our micro-method permitted assay of small samples (50-500 ng) such as a layer of cerebellar cortical nerve cells and of insulin producing cells from the islets of Langerhans. Although not reaching the high values in muscle, these cells showed significantly higher activities than parenchymatous cells from the liver and the exocrine pancreas. The sensitivity attained is more than required for assay of clinical fine needle biopsies and is quite satisfactory for detection and estimation of adenylate kinase contaminants in enzyme preparations."}
{"id": "PMID:208213", "title": "Altered in vitro adrenergic responses of dog detrusor msucle after chronic bladder outlet obstruction.", "content": "Muscle strips from the bladder body and dome of normal and control dogs usually demonstrate a relaxing (beta-adrenergic) response to norepinephrine. After bladder outlet obstruction was caused by urethral constriction, all body muscle strips from 7 of 12 dogs (58 per cent) demonstrated contractile (alpha-adrenergic) responses to norepinephrine. Bladder base muscle strips continued to show alpha-adrenergic responses. Desensitization or decreased beta-adrenergic receptor activity may play a part in causing the low compliance and detrusor instability seen in patients with bladder outlet obstruction.", "contents": "Altered in vitro adrenergic responses of dog detrusor msucle after chronic bladder outlet obstruction. Muscle strips from the bladder body and dome of normal and control dogs usually demonstrate a relaxing (beta-adrenergic) response to norepinephrine. After bladder outlet obstruction was caused by urethral constriction, all body muscle strips from 7 of 12 dogs (58 per cent) demonstrated contractile (alpha-adrenergic) responses to norepinephrine. Bladder base muscle strips continued to show alpha-adrenergic responses. Desensitization or decreased beta-adrenergic receptor activity may play a part in causing the low compliance and detrusor instability seen in patients with bladder outlet obstruction."}
{"id": "PMID:208214", "title": "Mediastinal extragonadal germ cell tumors.", "content": "Mediastinal germ cell tumors are a rare primary malignancy. An overview of the presenting clinical symptoms, radiographic appearance, patterns of extention and metastasis, and autopsy findings are presented. The difficulty in totally excluding an occult gonadal primary lesion in noted. The theories of the genesis of these tumors are briefly reviewed.", "contents": "Mediastinal extragonadal germ cell tumors. Mediastinal germ cell tumors are a rare primary malignancy. An overview of the presenting clinical symptoms, radiographic appearance, patterns of extention and metastasis, and autopsy findings are presented. The difficulty in totally excluding an occult gonadal primary lesion in noted. The theories of the genesis of these tumors are briefly reviewed."}
{"id": "PMID:208215", "title": "Ultrastructure of malignant paraganglioma of organ of Zuckerkandl.", "content": "Electron microscopic study of a malignant paraganglioma of the organ of Zuckerkandl revealed similarities between the tumor and the normal paraganglia. The well-differentiated portion of the tumor recapitulated the structure of the basic functional units of the paraganglion. In addition there signs of anaplasia both at the histologic and ultrastructural level. Large neurosecretory granules were noted in some of the tumor cells, but most of the cells were agranular. Crystaloids resembling those seen in alveolar soft part sarcoma were also noted. The study supports the theory on the common origin and histogenesis of paragangliomas and alveolar soft part sarcomas.", "contents": "Ultrastructure of malignant paraganglioma of organ of Zuckerkandl. Electron microscopic study of a malignant paraganglioma of the organ of Zuckerkandl revealed similarities between the tumor and the normal paraganglia. The well-differentiated portion of the tumor recapitulated the structure of the basic functional units of the paraganglion. In addition there signs of anaplasia both at the histologic and ultrastructural level. Large neurosecretory granules were noted in some of the tumor cells, but most of the cells were agranular. Crystaloids resembling those seen in alveolar soft part sarcoma were also noted. The study supports the theory on the common origin and histogenesis of paragangliomas and alveolar soft part sarcomas."}
{"id": "PMID:208217", "title": "[Isolation and detection of avian adenoviruses on cell cultures].", "content": "It is important, from the hygienic and epizootological view-point, to detect the presence of various microbiological agents in birds. The authors present the results of the virological examination of poultry, avian adenoviruses being the main object of investigation. Ninety-eight virus strains were isolated from chickens of different age categories and were included in the group of avian adenoviruses according to the form of cytopathic changes on the cell cultures of hen kidneys, according to the need for adaptation passages, chloroform, thermal, and pH resistance, character of nucleic acid, formation of intranuclear inclusions, and joint precipitation antigen, shared with the reference virus.", "contents": "[Isolation and detection of avian adenoviruses on cell cultures]. It is important, from the hygienic and epizootological view-point, to detect the presence of various microbiological agents in birds. The authors present the results of the virological examination of poultry, avian adenoviruses being the main object of investigation. Ninety-eight virus strains were isolated from chickens of different age categories and were included in the group of avian adenoviruses according to the form of cytopathic changes on the cell cultures of hen kidneys, according to the need for adaptation passages, chloroform, thermal, and pH resistance, character of nucleic acid, formation of intranuclear inclusions, and joint precipitation antigen, shared with the reference virus."}
{"id": "PMID:208220", "title": "[Immunofluorescence with the PI-3 virus--study of various working conditions for the detection of viral infection using immunofluorescence on various types of cell cultures].", "content": "We used the fluorescence method for the investigation of the sensitivity of several kinds of cell cultures to the infection with the parainfluenza virus 3 (PI-3). Cultures from calf kidneys were the most sensitive while we did not determine any differences between primary cultures and cultures of the first and second subpassages and/or freshly cultivated or incubated cultures over seven days at a temperature of 37 degrees C. Equal values of infection titres like on the cultures of calf kidneys were determined by immunofluorescence also on the kidney cells of lambs though the presence of  the infection was not accompanied by cytopathic changes. Infection of pig kidney cells appeared only after the inoculation of 10(3) TKID50 and higher doses of the virus, the infection having a very slow course of development without detectable cytopathic changes. Fluorescent findings were identical in different tissues. Antibodies present in the culture medium stopped the spreading of the infection by neutralizing the virus released from the cells, however, not the primary infection. The increase in the content of antibodies in the medium led - by inhibiting the intercellular virus - to the slowing down of the growth of primary fluorescent lesions.", "contents": "[Immunofluorescence with the PI-3 virus--study of various working conditions for the detection of viral infection using immunofluorescence on various types of cell cultures]. We used the fluorescence method for the investigation of the sensitivity of several kinds of cell cultures to the infection with the parainfluenza virus 3 (PI-3). Cultures from calf kidneys were the most sensitive while we did not determine any differences between primary cultures and cultures of the first and second subpassages and/or freshly cultivated or incubated cultures over seven days at a temperature of 37 degrees C. Equal values of infection titres like on the cultures of calf kidneys were determined by immunofluorescence also on the kidney cells of lambs though the presence of  the infection was not accompanied by cytopathic changes. Infection of pig kidney cells appeared only after the inoculation of 10(3) TKID50 and higher doses of the virus, the infection having a very slow course of development without detectable cytopathic changes. Fluorescent findings were identical in different tissues. Antibodies present in the culture medium stopped the spreading of the infection by neutralizing the virus released from the cells, however, not the primary infection. The increase in the content of antibodies in the medium led - by inhibiting the intercellular virus - to the slowing down of the growth of primary fluorescent lesions."}
{"id": "PMID:208221", "title": "Comparative study of experimental inclusion body hepatitis of chickens caused by two serotypes of avian adenovirus.", "content": "Twenty 1-day-old specific-pathogen-free chickens each were given an intraabdominal inoculation of either a type-8 avian adenovirus, [AMG 5 (2a], or a type-5 avian adenovirus, inclusion body hepatitis virus (IBHV). The diseases produced were similar. High (60-100%) mortality and statistically significant depression of body weights occurred in both infections. There were necrotizing hepatitis and pancreatitis, lymphoid depletion in the spleen, bursa of Fabricius and thymus, hydropericardium, nephritis and enteritis. Intranuclear inclusions occurred in affected organs. Fluorescent-antibody staining, the Feulgen reaction for deoxyribonucleic acid and electron microscopic studies, as well as studies from the literature, indicated that basophilic inclusions consisted of assembled adenovirions.", "contents": "Comparative study of experimental inclusion body hepatitis of chickens caused by two serotypes of avian adenovirus. Twenty 1-day-old specific-pathogen-free chickens each were given an intraabdominal inoculation of either a type-8 avian adenovirus, [AMG 5 (2a], or a type-5 avian adenovirus, inclusion body hepatitis virus (IBHV). The diseases produced were similar. High (60-100%) mortality and statistically significant depression of body weights occurred in both infections. There were necrotizing hepatitis and pancreatitis, lymphoid depletion in the spleen, bursa of Fabricius and thymus, hydropericardium, nephritis and enteritis. Intranuclear inclusions occurred in affected organs. Fluorescent-antibody staining, the Feulgen reaction for deoxyribonucleic acid and electron microscopic studies, as well as studies from the literature, indicated that basophilic inclusions consisted of assembled adenovirions."}
{"id": "PMID:208222", "title": "Pathological changes in the small intestine of neonatal calves naturally infected with reo-like virus (rotavirus).", "content": "Nine calves, of which six had been challenged with an enteropathogenic strain of Escherichia coli, were found to be naturally infected with rotavirus. Rotavirus was recovered from the faeces of six calves and rotavirus antigen was detected in the intestinal mucosa of all calves. Stunting and fusion of villi were seen principally in the proximal and middle small intestine, where rotavirus antigen was detected by immunofluorescence. Typical lesions of enteric colibacillosis were found in the distal ileum of the challenged calves, associated with adhesion of the challenge strain of E coli to the mucosa. All samples were removed from the intestine under general anaesthesia and denudation of villi was not observed. However, following exsanguination and resampling at the same site in the small intestine of one calf, denudation was a constant feature.", "contents": "Pathological changes in the small intestine of neonatal calves naturally infected with reo-like virus (rotavirus). Nine calves, of which six had been challenged with an enteropathogenic strain of Escherichia coli, were found to be naturally infected with rotavirus. Rotavirus was recovered from the faeces of six calves and rotavirus antigen was detected in the intestinal mucosa of all calves. Stunting and fusion of villi were seen principally in the proximal and middle small intestine, where rotavirus antigen was detected by immunofluorescence. Typical lesions of enteric colibacillosis were found in the distal ileum of the challenged calves, associated with adhesion of the challenge strain of E coli to the mucosa. All samples were removed from the intestine under general anaesthesia and denudation of villi was not observed. However, following exsanguination and resampling at the same site in the small intestine of one calf, denudation was a constant feature."}
{"id": "PMID:208226", "title": "[Intracristal linear inclusions in mitochondria of human rhabdomyoma cells (author's transl)].", "content": "Electron microscopic study of a rhabdomyoma of the soft palate of a 50-year-old woman revealed linear structures within the intracristal spaces of mitochondria. In the center of most cristae, an electron-dense line was found located in parallel arrangement to the limiting cristal membrane. The linear inclusion was separated from the cristal membrane by a narrow space of lower electron-density. Thus, when sectioned longitudinally, the abnormal cristae exhibited a pentalaminar appearance. Additionally, they were characterized by a greater diameter than that of normal cristae and a \"rigid\" configuration. Higher magnification showed that the intracristal line consisted of a row of periodically arranged, electron-dense dots. Sometimes, these seemed to be connected with the wall of the intracristal space by fine, electron-dense cross-striations. In some mitochondria of rhabdomyoma cells, crystals with a linear substructure were observed in both intra- and extracristal spaces. The crystalline bodies located within cristae had probably been formed by accumulation of linear inclusions. The extracristal bodies seemed to have arisen from fusion of pentalaminar cristae. It is supposed that the intracristal linear inclusions in mitochondria of rhabdomyoma cells represent crystallized proteins of mitochondrial enzymes.", "contents": "[Intracristal linear inclusions in mitochondria of human rhabdomyoma cells (author's transl)]. Electron microscopic study of a rhabdomyoma of the soft palate of a 50-year-old woman revealed linear structures within the intracristal spaces of mitochondria. In the center of most cristae, an electron-dense line was found located in parallel arrangement to the limiting cristal membrane. The linear inclusion was separated from the cristal membrane by a narrow space of lower electron-density. Thus, when sectioned longitudinally, the abnormal cristae exhibited a pentalaminar appearance. Additionally, they were characterized by a greater diameter than that of normal cristae and a \"rigid\" configuration. Higher magnification showed that the intracristal line consisted of a row of periodically arranged, electron-dense dots. Sometimes, these seemed to be connected with the wall of the intracristal space by fine, electron-dense cross-striations. In some mitochondria of rhabdomyoma cells, crystals with a linear substructure were observed in both intra- and extracristal spaces. The crystalline bodies located within cristae had probably been formed by accumulation of linear inclusions. The extracristal bodies seemed to have arisen from fusion of pentalaminar cristae. It is supposed that the intracristal linear inclusions in mitochondria of rhabdomyoma cells represent crystallized proteins of mitochondrial enzymes."}
{"id": "PMID:208227", "title": "Chemodectoma of the larynx. A clinico-pathological study.", "content": "The present case report is concerned with a clinico-pathological study, including ultrastructural investigation, of a rare and uncommon laryngeal tumour, a chemodectoma, in a 62 year old patient. There have been 23 cases of laryngeal chemodectomas reported in the literature, and only three of them, including our own report, were investigated by electron microscopy. The tumours arise from the superior and inferior larynegeal nonchromaffin paraganglia or possibly from Kultschitzky-cells of the normal bronchial mucosa. Ultrastructurally they have all the characteristics of apudomas whose parent cells (APUD-cells), usually show endocrine function and probably have their origin in the neural crest. The tumours show an aggressive type of behaviour, despite usually benign histological features when compared to chemodectomas at other sites in the head and neck region. Surgery is thus the therapy of choice.", "contents": "Chemodectoma of the larynx. A clinico-pathological study. The present case report is concerned with a clinico-pathological study, including ultrastructural investigation, of a rare and uncommon laryngeal tumour, a chemodectoma, in a 62 year old patient. There have been 23 cases of laryngeal chemodectomas reported in the literature, and only three of them, including our own report, were investigated by electron microscopy. The tumours arise from the superior and inferior larynegeal nonchromaffin paraganglia or possibly from Kultschitzky-cells of the normal bronchial mucosa. Ultrastructurally they have all the characteristics of apudomas whose parent cells (APUD-cells), usually show endocrine function and probably have their origin in the neural crest. The tumours show an aggressive type of behaviour, despite usually benign histological features when compared to chemodectomas at other sites in the head and neck region. Surgery is thus the therapy of choice."}
{"id": "PMID:208228", "title": "Androgen producing adrenocortical carcinoma.", "content": "Two cases of androgen secreting adrenocortical carcinoma have been described by light and electron microscopy. The histological and ultrastructural features of the tumour cells were similar to those of compact cells of zona reticularis and to those described in virilizing adenomas. They possess numerous mitochondria with lamellar and tubular cristae, abundant smooth endoplasmic reticulum, lipofuscin bodies and scanty lipid. Irregularly shaped, crenated mitochondria, with outpouchings of the outer limiting membrane have also been observed. The clusters of neoplastic cells were surrounded by basement membrane which demonstrated a focal discontinuity, probably reflecting malignancy of the tumours. Hyperplasia of smooth endoplasmic reticulum and the presence of outpouchings of the mitochondrial outer limiting membrane might be the morphological manifestation of endocrine activity of the tumours.", "contents": "Androgen producing adrenocortical carcinoma. Two cases of androgen secreting adrenocortical carcinoma have been described by light and electron microscopy. The histological and ultrastructural features of the tumour cells were similar to those of compact cells of zona reticularis and to those described in virilizing adenomas. They possess numerous mitochondria with lamellar and tubular cristae, abundant smooth endoplasmic reticulum, lipofuscin bodies and scanty lipid. Irregularly shaped, crenated mitochondria, with outpouchings of the outer limiting membrane have also been observed. The clusters of neoplastic cells were surrounded by basement membrane which demonstrated a focal discontinuity, probably reflecting malignancy of the tumours. Hyperplasia of smooth endoplasmic reticulum and the presence of outpouchings of the mitochondrial outer limiting membrane might be the morphological manifestation of endocrine activity of the tumours."}
{"id": "PMID:208229", "title": "Deviated formation of intestinal glycocalyx in human stomach cancer cells. Another type of signet ring cell.", "content": "The process of glycocalyx formation by the trilaminar membrane was investigated at the subcellular level by use of cultivated cancer cells derived from a human stomach adenocarcinoma. Glycocalyx was apparently synthesized on the characteristic trilaminar membrane of Golgi-derived vesicles which gave rise to cytoplasmic vacuoles which, in turn, fused to form an intracytoplasmic cyst. Characteristic microvilli similar to those of intestinal epithelium extended from the membrane lining the intracytoplasmic cyst. These ultrastructural features agree with earlier histochemical findings in suggesting intestinal metaplasia in the origin of the gastric tumor. The morphologic features of the cancer cells clearly indicated that glycoprotein is first synthesized in the Golgi complex and fully formed mucoprotein then emerges as membrane-bound glycocalyx in the vesicles budding from the Golgi stacks. The glycocalyx layer is an integral part of the external leaflet of the characteristic trilaminar membrane. Abundant deposits of glycocalyx in the intracytoplasmic cyst constituted the ultrastructural basis for a distinctive type of signet ring cell that differed from mucous signet ring cells derived from goblet cells.", "contents": "Deviated formation of intestinal glycocalyx in human stomach cancer cells. Another type of signet ring cell. The process of glycocalyx formation by the trilaminar membrane was investigated at the subcellular level by use of cultivated cancer cells derived from a human stomach adenocarcinoma. Glycocalyx was apparently synthesized on the characteristic trilaminar membrane of Golgi-derived vesicles which gave rise to cytoplasmic vacuoles which, in turn, fused to form an intracytoplasmic cyst. Characteristic microvilli similar to those of intestinal epithelium extended from the membrane lining the intracytoplasmic cyst. These ultrastructural features agree with earlier histochemical findings in suggesting intestinal metaplasia in the origin of the gastric tumor. The morphologic features of the cancer cells clearly indicated that glycoprotein is first synthesized in the Golgi complex and fully formed mucoprotein then emerges as membrane-bound glycocalyx in the vesicles budding from the Golgi stacks. The glycocalyx layer is an integral part of the external leaflet of the characteristic trilaminar membrane. Abundant deposits of glycocalyx in the intracytoplasmic cyst constituted the ultrastructural basis for a distinctive type of signet ring cell that differed from mucous signet ring cells derived from goblet cells."}
{"id": "PMID:208230", "title": "Anterior polar cataract and lysosomal alterations in the lens of rats treated with the amphiphilic lipidosis-inducing drugs chloroquine and chlorphentermine.", "content": "Chronic treatment of rats with the amphipilic drugs chloroquine and chlorphentermine caused prominent anterior polar cataracts in virtually all rats. The basic pathologic changes underlying these cataracts were: (a) degeneration of anterior polar and sutural endings of cortical lens cells and (b) multilayered proliferation and invasion of epithelial cells into the anterior polar cortex. Ultrastructurally cortical lens cells displayed various patterns of degeneration, finally undergoing complete liquification. Liquified lens substance was phagocytosed by invading epithelial cells. Cortical lens cells and epithelial cells contained numerous lipidosis-like (lamellated) inclusions, which possessed cytochemical acid phosphatase activity. The present drug-induced lenticular alterations are interpreted as the direct or indirect consequences of a drug-induced disturbance of polar lipid metabolism in the lens.", "contents": "Anterior polar cataract and lysosomal alterations in the lens of rats treated with the amphiphilic lipidosis-inducing drugs chloroquine and chlorphentermine. Chronic treatment of rats with the amphipilic drugs chloroquine and chlorphentermine caused prominent anterior polar cataracts in virtually all rats. The basic pathologic changes underlying these cataracts were: (a) degeneration of anterior polar and sutural endings of cortical lens cells and (b) multilayered proliferation and invasion of epithelial cells into the anterior polar cortex. Ultrastructurally cortical lens cells displayed various patterns of degeneration, finally undergoing complete liquification. Liquified lens substance was phagocytosed by invading epithelial cells. Cortical lens cells and epithelial cells contained numerous lipidosis-like (lamellated) inclusions, which possessed cytochemical acid phosphatase activity. The present drug-induced lenticular alterations are interpreted as the direct or indirect consequences of a drug-induced disturbance of polar lipid metabolism in the lens."}
{"id": "PMID:208285", "title": "[Effect of the prolonged administration of the atherogenic fractions of lipoproteins on the blood and myocardial lipid picture in rabbits].", "content": "Homologous total fraction of pre-beta and beta-lipoproteins, isolated from intact animal blood and administered intravenously into rabbits within 1.5-2 months, caused distinct alterations in lipid spectra of rabbit-recipient blood serum. The phenomenon was manifested as an increase in concentration of all the lipid components in blood plasma, elevation in content of pre-beta and beta-lipoproteins in blood and decrease in content of alpha-lipoproteins. The alterations were apparently related not only to excessive administration of atherogenic lipoproteins but to impairments in lipid metabolism, similar to lipoproteinemia, reproduced in other experiments.", "contents": "[Effect of the prolonged administration of the atherogenic fractions of lipoproteins on the blood and myocardial lipid picture in rabbits]. Homologous total fraction of pre-beta and beta-lipoproteins, isolated from intact animal blood and administered intravenously into rabbits within 1.5-2 months, caused distinct alterations in lipid spectra of rabbit-recipient blood serum. The phenomenon was manifested as an increase in concentration of all the lipid components in blood plasma, elevation in content of pre-beta and beta-lipoproteins in blood and decrease in content of alpha-lipoproteins. The alterations were apparently related not only to excessive administration of atherogenic lipoproteins but to impairments in lipid metabolism, similar to lipoproteinemia, reproduced in other experiments."}
{"id": "PMID:208286", "title": "[Effect of psychotropic preparations on cyclic AMP phosphodiesterase activity in the rat cerebral cortex].", "content": "Effect of various psychotropic preparations on cAMP phosphodiesterase was studied. Almost all the psychotropic drugs studied were shown to inhibit the enzymatic activity. Neuroleptics--derivatives of phenothiazine and butyrophene--caused the strongest inhibitory effect.", "contents": "[Effect of psychotropic preparations on cyclic AMP phosphodiesterase activity in the rat cerebral cortex]. Effect of various psychotropic preparations on cAMP phosphodiesterase was studied. Almost all the psychotropic drugs studied were shown to inhibit the enzymatic activity. Neuroleptics--derivatives of phenothiazine and butyrophene--caused the strongest inhibitory effect."}
{"id": "PMID:208288", "title": "[Enzymatic mechanisms for antimicrobial protection of the oral cavity].", "content": "Data on the role of oral lysozyme, ribonuclease, deoxyribonuclease and peroxidase in antimicrobial defense of the macroorganism are reviewed. The biochemical and physiological properties of the enzymes secreted by salivary glands and released from emigrating leukocytes are discussed. Spectra of antimicrobial action of the enzymes and participation of these enzymes in maintaining the stability of oral biocenosis are described as well as the regulation of these enzymatic activities and the pathogenetic significance of impairments in their secretion. The most perspective aspects of the problems discussed are outlined for further investigation.", "contents": "[Enzymatic mechanisms for antimicrobial protection of the oral cavity]. Data on the role of oral lysozyme, ribonuclease, deoxyribonuclease and peroxidase in antimicrobial defense of the macroorganism are reviewed. The biochemical and physiological properties of the enzymes secreted by salivary glands and released from emigrating leukocytes are discussed. Spectra of antimicrobial action of the enzymes and participation of these enzymes in maintaining the stability of oral biocenosis are described as well as the regulation of these enzymatic activities and the pathogenetic significance of impairments in their secretion. The most perspective aspects of the problems discussed are outlined for further investigation."}
{"id": "PMID:208287", "title": "[Thymidine phosphorylation with the participation of rat thymic and hepatic thymidine kinase in the presence of a factor from Cl. perfringens (welchii)].", "content": "Factor CPW, isolated from Cl. perfringens/welchii was shown to activate latent thymidine kinase (factor N) from liver tissue of rats beginning from 42 days age. CPW factor activated 3.5-fold also thymidine kinase from rat strumous gland; the enzyme was observed during involution of the tissue. The data suggest that increase in thymidine kinase activity in proliferating tissues is related to activation of latent enzymes.", "contents": "[Thymidine phosphorylation with the participation of rat thymic and hepatic thymidine kinase in the presence of a factor from Cl. perfringens (welchii)]. Factor CPW, isolated from Cl. perfringens/welchii was shown to activate latent thymidine kinase (factor N) from liver tissue of rats beginning from 42 days age. CPW factor activated 3.5-fold also thymidine kinase from rat strumous gland; the enzyme was observed during involution of the tissue. The data suggest that increase in thymidine kinase activity in proliferating tissues is related to activation of latent enzymes."}
{"id": "PMID:208289", "title": "[Reactions of tumor and organs of tumor-bearing animals to administration of a synthetic antioxidant].", "content": "Alterations of lipid antioxidative activity in liver and tumor as well as change in weight of spleen and tumor were studied in mice with hepatoma-22 after administration of synthetic antioxidant 4-methyl-2,6-ditertbutylphenol (ionol) at doses 30 mg/kg and 100 mg/kg during the 6th day of growth of the tumor. Lipid antioxidative activity was shown to respond similarly to administration of ionol in liver tissue of both the intact and tumor-bearing animals. The antioxidative activity was increased after administration of these doses of the antioxidant, then the antioxidative activity was decreased down to the initial level when the dose 30 mg/kg was used and below this level--at the dose 100 mg/kg. Both doses of the drug increased the lipid antioxidative activity in tumor. The dose 30 mg/kg of ionol stimulated the growth of the tumor and increased the weight of spleen in tumor-bearing animals and the dose 100 mg/kg--inhibited these parameters. Regulation of oxidation of the lipids in tumor appears to be impaired or altered to another level as compared with the oxidation of lipids in normal tissues or in the tissues of tumor-bearing animals.", "contents": "[Reactions of tumor and organs of tumor-bearing animals to administration of a synthetic antioxidant]. Alterations of lipid antioxidative activity in liver and tumor as well as change in weight of spleen and tumor were studied in mice with hepatoma-22 after administration of synthetic antioxidant 4-methyl-2,6-ditertbutylphenol (ionol) at doses 30 mg/kg and 100 mg/kg during the 6th day of growth of the tumor. Lipid antioxidative activity was shown to respond similarly to administration of ionol in liver tissue of both the intact and tumor-bearing animals. The antioxidative activity was increased after administration of these doses of the antioxidant, then the antioxidative activity was decreased down to the initial level when the dose 30 mg/kg was used and below this level--at the dose 100 mg/kg. Both doses of the drug increased the lipid antioxidative activity in tumor. The dose 30 mg/kg of ionol stimulated the growth of the tumor and increased the weight of spleen in tumor-bearing animals and the dose 100 mg/kg--inhibited these parameters. Regulation of oxidation of the lipids in tumor appears to be impaired or altered to another level as compared with the oxidation of lipids in normal tissues or in the tissues of tumor-bearing animals."}
{"id": "PMID:208290", "title": "[Characteristics of L-threonine- and L-serine dehydratases from mouse liver and spontaneous hepatomas].", "content": "High activities of L-threonine and l-serine dehydratases were maintained in spontaneous hepatoma of mice strain CBA as distinct from transplantable hepatoma. The initial rate [v] versus substrate concentration [S]0 curves had complex shapes for the enzymes from the liver tissue of healthy animals (especially after extraction of the enzymes by means of buffers with low concentration of K+). Kinetic patterns of l-threonine and L-serine dehydratases from hepatoma were distinct from those of normal mice liver tissue. The shape of [v] versus [S]0 plots was altered in response to AMP (1.10(-3) M). Contrary to the enzymes from normal tissue, dehydratases from hepatoma did not alter the shape of [v] versus [S]0 curves in response to AMP. The enzymes from hepatoma were apparently desensitized with respect to their possible allosteric effector. Threonine dehydratases of normal mice liver were also dissimilar as compared with the enzymes from hepatoma in the affinity of the apoenzyme to pyridoxal 5'-phosphate. This affinity was 3-fold lower for threonine dehydratase from hepatoma as compared with the enzyme from liver tissue.", "contents": "[Characteristics of L-threonine- and L-serine dehydratases from mouse liver and spontaneous hepatomas]. High activities of L-threonine and l-serine dehydratases were maintained in spontaneous hepatoma of mice strain CBA as distinct from transplantable hepatoma. The initial rate [v] versus substrate concentration [S]0 curves had complex shapes for the enzymes from the liver tissue of healthy animals (especially after extraction of the enzymes by means of buffers with low concentration of K+). Kinetic patterns of l-threonine and L-serine dehydratases from hepatoma were distinct from those of normal mice liver tissue. The shape of [v] versus [S]0 plots was altered in response to AMP (1.10(-3) M). Contrary to the enzymes from normal tissue, dehydratases from hepatoma did not alter the shape of [v] versus [S]0 curves in response to AMP. The enzymes from hepatoma were apparently desensitized with respect to their possible allosteric effector. Threonine dehydratases of normal mice liver were also dissimilar as compared with the enzymes from hepatoma in the affinity of the apoenzyme to pyridoxal 5'-phosphate. This affinity was 3-fold lower for threonine dehydratase from hepatoma as compared with the enzyme from liver tissue."}
{"id": "PMID:208291", "title": "[Method of preparing a radioactive collagen substrate from chick embryo tendons for determining the activity of collagenases of animal origin].", "content": "A method, described for obtaining of 14C-collagen from chicken embryo tendons, permitted to isolate the highly purified native substrate with high specific radioactivity applied to estimation of animal collagenases activity. The method is relatively simple, reproducible, does not require large amount of labelled amino acids; it shortens the course of protein purification.", "contents": "[Method of preparing a radioactive collagen substrate from chick embryo tendons for determining the activity of collagenases of animal origin]. A method, described for obtaining of 14C-collagen from chicken embryo tendons, permitted to isolate the highly purified native substrate with high specific radioactivity applied to estimation of animal collagenases activity. The method is relatively simple, reproducible, does not require large amount of labelled amino acids; it shortens the course of protein purification."}
{"id": "PMID:208292", "title": "[Electron-autoradiographic and biochemical study of the role of foam cells in low density lipoprotein metabolism].", "content": "Participation of foam cells in metabolism of lipoproteins of low density (LPLD) was studied by biochemical methods and by electronic autoradiography. The foam cells were isolated from atherosclerotic rabbit aorta after perfusion with 12I-LPLD within 6 hrs. Metabolic activity of foam cells was evaluated by the ratio of radioactivity in lipid and protein components of cells as well as by distribution of reduced argentum granules among the subcellular structures on autoradiogram. The biochemical studies showed that the lipid components of LPLD were preferably accumulated in foam cells. Electronic-autoradiography demonstrated that protein from the lipoprotein particles was also distributed intracellularly in various cytoplasmic structures. Foam cells appear to capture intact lipoprotein particles by pinocytosis with subsequent splitting of protein component by cellular lysosome apparatus.", "contents": "[Electron-autoradiographic and biochemical study of the role of foam cells in low density lipoprotein metabolism]. Participation of foam cells in metabolism of lipoproteins of low density (LPLD) was studied by biochemical methods and by electronic autoradiography. The foam cells were isolated from atherosclerotic rabbit aorta after perfusion with 12I-LPLD within 6 hrs. Metabolic activity of foam cells was evaluated by the ratio of radioactivity in lipid and protein components of cells as well as by distribution of reduced argentum granules among the subcellular structures on autoradiogram. The biochemical studies showed that the lipid components of LPLD were preferably accumulated in foam cells. Electronic-autoradiography demonstrated that protein from the lipoprotein particles was also distributed intracellularly in various cytoplasmic structures. Foam cells appear to capture intact lipoprotein particles by pinocytosis with subsequent splitting of protein component by cellular lysosome apparatus."}
{"id": "PMID:208298", "title": "[Lymphography and the possibility of tumor cell dissemination].", "content": "It is concluded that endolymphatic infusion of X-ray contrast substance in the presence of migrating tumor cells in lymphatic routes is inherent in a potential danger of tumor dissemination. Although getting of tumor cells in blood does not always result in metastases, nevertheless, a due account should be taken of the fact that lymphography is frequently performed in poor immunological resistance patients, preliminarily subjected to chemo- and radiotherapy. The decrease of immune resistance of the organism, in which the lymphatic system is of primary importance, is known to contribute per se to generalization of the tumor process. Another important conclusion is that the principal mass of tumor cells is ejected in the immediate period after endolymphatic injection of X-ray contrast substance. Thus, the cannulation of the thoracic duct during this period may prevent or reduce getting of massive amounts of tumor cells into the total blood flow.", "contents": "[Lymphography and the possibility of tumor cell dissemination]. It is concluded that endolymphatic infusion of X-ray contrast substance in the presence of migrating tumor cells in lymphatic routes is inherent in a potential danger of tumor dissemination. Although getting of tumor cells in blood does not always result in metastases, nevertheless, a due account should be taken of the fact that lymphography is frequently performed in poor immunological resistance patients, preliminarily subjected to chemo- and radiotherapy. The decrease of immune resistance of the organism, in which the lymphatic system is of primary importance, is known to contribute per se to generalization of the tumor process. Another important conclusion is that the principal mass of tumor cells is ejected in the immediate period after endolymphatic injection of X-ray contrast substance. Thus, the cannulation of the thoracic duct during this period may prevent or reduce getting of massive amounts of tumor cells into the total blood flow."}
{"id": "PMID:208299", "title": "[Treatment of phylloid tumors of the breast].", "content": "Phylloid fibroadenoma of the mammary gland is a comparatively rare lesion--0.3% of all breast affections, its clinical course is generally known to be characterized by both the possibility of recurrences development after non-radical treatment and its transition into mammary gland sarcoma. The authors report the data on 56 cases of phylloid fibroadenoma of the mammary gland treated at the N.N. Petrov Research Institute of Oncology of the USSR Ministry of Health during the period of 1926 to 1973. Fifty one of these patients showed benign tumors, 5--malignant tumors. The clinical diagnosis of the tumor is rather complicated (the correct preoperative diagnosis was established only in 27.5% of cases). The use of non-contrast mammography and trepanbiopsy failed to appreciably improve the diagnosis. The differential diagnosis between the benign and malignant forms seems to be mostly difficult. Only surgery is advocated. The extent of surgical intervention depends on morphological features of the tumor, its size, rate of growth and the breast size. Among benign forms recurrences were noted in three patients (6.3%). Of 5 patients with malignant phylloid fibroadenoma two patients died due to metastases during two postoperative years.", "contents": "[Treatment of phylloid tumors of the breast]. Phylloid fibroadenoma of the mammary gland is a comparatively rare lesion--0.3% of all breast affections, its clinical course is generally known to be characterized by both the possibility of recurrences development after non-radical treatment and its transition into mammary gland sarcoma. The authors report the data on 56 cases of phylloid fibroadenoma of the mammary gland treated at the N.N. Petrov Research Institute of Oncology of the USSR Ministry of Health during the period of 1926 to 1973. Fifty one of these patients showed benign tumors, 5--malignant tumors. The clinical diagnosis of the tumor is rather complicated (the correct preoperative diagnosis was established only in 27.5% of cases). The use of non-contrast mammography and trepanbiopsy failed to appreciably improve the diagnosis. The differential diagnosis between the benign and malignant forms seems to be mostly difficult. Only surgery is advocated. The extent of surgical intervention depends on morphological features of the tumor, its size, rate of growth and the breast size. Among benign forms recurrences were noted in three patients (6.3%). Of 5 patients with malignant phylloid fibroadenoma two patients died due to metastases during two postoperative years."}
{"id": "PMID:208295", "title": "[Nature of the lipoprotein antigen responsible for the development of resistance to experimental atherosclerosis following its use in immunization of newborn rabbits].", "content": "In order to develop a tolerance to experimental atherosclerosis newborn rabbits were immunized with various fractions of atherogenic lipoproteins (lipoproteins of low density, lipoproteins of very low density and total fraction of these lipoproteins), isolated from blood serum of adult rabbits with experimental hypercholesterolemia. The tolerance to atherosclerosis proved to be achieved in immunization with lipoproteins of very low density. The lesser effect was observed using the total fraction of lipoproteins. The tolerance was not developed in immunization with lipoproteins of low density.", "contents": "[Nature of the lipoprotein antigen responsible for the development of resistance to experimental atherosclerosis following its use in immunization of newborn rabbits]. In order to develop a tolerance to experimental atherosclerosis newborn rabbits were immunized with various fractions of atherogenic lipoproteins (lipoproteins of low density, lipoproteins of very low density and total fraction of these lipoproteins), isolated from blood serum of adult rabbits with experimental hypercholesterolemia. The tolerance to atherosclerosis proved to be achieved in immunization with lipoproteins of very low density. The lesser effect was observed using the total fraction of lipoproteins. The tolerance was not developed in immunization with lipoproteins of low density."}
{"id": "PMID:208296", "title": "[Comparative lecithin-cholesterol-acyltransferase deficiency in the blood of newborn infants. Comparison of the esterifying activity of neonatal and maternal blood].", "content": "On the basis of data obtained in studies on the accumulation of cholesterol in erythrocytes of newlorns, the hypothesis is advanced on the deficiency of lecithin-cholesterol-acetyl transferase (LCAT) in the newborn children. A decrease in the rate of the LCAT-reaction was shown in funic blood using the specially developed system \"LP-infranatante\", the constituents of which were isolated from blood plasma of both newborns and of their mothers by ultracentrifugation at a density 1.21 g/ml and 40.000 rpm. The following factors were considered as possible determinants of the decrease in the rate of cholesterol esterification in blood plasma of newborns: 1) insufficiency in LCAT, 2) alteration in the composition of the substrate lipoproteins (lipoproteins of high density).", "contents": "[Comparative lecithin-cholesterol-acyltransferase deficiency in the blood of newborn infants. Comparison of the esterifying activity of neonatal and maternal blood]. On the basis of data obtained in studies on the accumulation of cholesterol in erythrocytes of newlorns, the hypothesis is advanced on the deficiency of lecithin-cholesterol-acetyl transferase (LCAT) in the newborn children. A decrease in the rate of the LCAT-reaction was shown in funic blood using the specially developed system \"LP-infranatante\", the constituents of which were isolated from blood plasma of both newborns and of their mothers by ultracentrifugation at a density 1.21 g/ml and 40.000 rpm. The following factors were considered as possible determinants of the decrease in the rate of cholesterol esterification in blood plasma of newborns: 1) insufficiency in LCAT, 2) alteration in the composition of the substrate lipoproteins (lipoproteins of high density)."}
{"id": "PMID:208294", "title": "[Synthesis of RNA fractions in rat liver during single and multiple stimulation of the hypothalamus].", "content": "Specific radioactivity of RNA from rat liver tissue, labelled with 14C-orotic acid and fractionated using thermic phenol method, was altered dissimilarly. In single stimulation of hypothalamus the specific radioactivity of nuclear RNA was increased in RNA-40 degrees fraction than in RNA-55 degrees and RNA-63 degrees ones. A decrease in synthesis of nuclear RNA fractions followed the phase of activation in repeated stimulation of hypothalamus. The distinct increase in specific radioactivity was observed in cytoplasmic RNA (RNA-4 degrees) both in single and repeated stimulation of hypothalamus. The stimulating effect of the prolonged hypothalamus irritation on synthesis of the RNA fractions and on activity of glucose-6-phosphatase and fructose-1,6-diphosphatase disappeared more rapidly than this effect in long-term administration of hydrocortisone. The data obtained suggest that sensitivity of tissue-targets to prolonged hormonal stimulation is distinctly higher than the ability of hypothalamus to activate the synthesis of RNA and enzymatic proteins.", "contents": "[Synthesis of RNA fractions in rat liver during single and multiple stimulation of the hypothalamus]. Specific radioactivity of RNA from rat liver tissue, labelled with 14C-orotic acid and fractionated using thermic phenol method, was altered dissimilarly. In single stimulation of hypothalamus the specific radioactivity of nuclear RNA was increased in RNA-40 degrees fraction than in RNA-55 degrees and RNA-63 degrees ones. A decrease in synthesis of nuclear RNA fractions followed the phase of activation in repeated stimulation of hypothalamus. The distinct increase in specific radioactivity was observed in cytoplasmic RNA (RNA-4 degrees) both in single and repeated stimulation of hypothalamus. The stimulating effect of the prolonged hypothalamus irritation on synthesis of the RNA fractions and on activity of glucose-6-phosphatase and fructose-1,6-diphosphatase disappeared more rapidly than this effect in long-term administration of hydrocortisone. The data obtained suggest that sensitivity of tissue-targets to prolonged hormonal stimulation is distinctly higher than the ability of hypothalamus to activate the synthesis of RNA and enzymatic proteins."}
{"id": "PMID:208301", "title": "[Effect of rations with an increased sunflower seed oil level on the rate of very low-density lipoprotein formation in the liver, secretion into the blood and composition in the blood].", "content": "Feeding of rats on a ration with an excessive content of sunflower-oil (60 per cent of the total calorific value of the ration) for a period of 30 days resulted in lowering the rate of the apoproteins, prolipoproteins synthesis in the liver and in their loading with triglycerides and cholesterol. As a consequence of this it diminished secretion of endogenously formed tryglycerides and cholesterol from the liver into the blood and a changed lipid composition of lipoproteins of a very low density in the blood.", "contents": "[Effect of rations with an increased sunflower seed oil level on the rate of very low-density lipoprotein formation in the liver, secretion into the blood and composition in the blood]. Feeding of rats on a ration with an excessive content of sunflower-oil (60 per cent of the total calorific value of the ration) for a period of 30 days resulted in lowering the rate of the apoproteins, prolipoproteins synthesis in the liver and in their loading with triglycerides and cholesterol. As a consequence of this it diminished secretion of endogenously formed tryglycerides and cholesterol from the liver into the blood and a changed lipid composition of lipoproteins of a very low density in the blood."}
{"id": "PMID:208304", "title": "Conceptual framework shifts in immunogenetics. II. Some notes on the Ag system.", "content": "Two Caucasian population materials totalling 530 individuals and 3,180 typing results are analyzed with regard to various combinations of the Ag(x, y, a1, d, c, g) factors. Superficially, both materials appear well aligned to each other and the contemporary (simple-complex) framework. However, when the same set of data are structuralized within a new (complex-simple) framework, the typing results for 12 of 362 or 3.3% of the Swiss and no less than 19 of 168 or 11.3% of the English samples are not compatible with the new framework specifying that the various anti-Ag reagents can be arranged in two 'inclusion groups'--the anti-Ag (y greater than d greater than c) and the anti-Ag (g greater than a1 greater than x) series.", "contents": "Conceptual framework shifts in immunogenetics. II. Some notes on the Ag system. Two Caucasian population materials totalling 530 individuals and 3,180 typing results are analyzed with regard to various combinations of the Ag(x, y, a1, d, c, g) factors. Superficially, both materials appear well aligned to each other and the contemporary (simple-complex) framework. However, when the same set of data are structuralized within a new (complex-simple) framework, the typing results for 12 of 362 or 3.3% of the Swiss and no less than 19 of 168 or 11.3% of the English samples are not compatible with the new framework specifying that the various anti-Ag reagents can be arranged in two 'inclusion groups'--the anti-Ag (y greater than d greater than c) and the anti-Ag (g greater than a1 greater than x) series."}
{"id": "PMID:208305", "title": "[Foamy viruses in baboons and macaques].", "content": "The occurrence of foamy viruses among baboons and macaca monkeys in Sukhumi monkey farm was investigate;. The monkeys were shown to be carriers mainly of foamy virus type II. The frequency of virus isolation increased with the age of the animals and reached 88.8-100% in adult specimens. The virus behaviour in cell cultures is described. The morphological characteristics of the virus are based on electron microscopic examinations of ultrathin sections of primary and inoculated cell cultures.", "contents": "[Foamy viruses in baboons and macaques]. The occurrence of foamy viruses among baboons and macaca monkeys in Sukhumi monkey farm was investigate;. The monkeys were shown to be carriers mainly of foamy virus type II. The frequency of virus isolation increased with the age of the animals and reached 88.8-100% in adult specimens. The virus behaviour in cell cultures is described. The morphological characteristics of the virus are based on electron microscopic examinations of ultrathin sections of primary and inoculated cell cultures."}
{"id": "PMID:208307", "title": "[Enzymatic activity of the lymphocytes in gnotobionts in adenovirus infection].", "content": "The cytochemical activity of succinate dehydrogenases, alpha-glycerophosphate (mitochondrial and hyaloplasmic), lactate, glycose-6-phosphate, glutamate, beta-oxibutyrate, NADP-H2- and NAD-H2 diaphorases and acid phosphatase was studied in lymphocytes of gnotobiotic guinea-pigs infected with human adenovirus type 1. The analysis of transgression of distribution of the values in the experimental and control groups revealed a high informative diagnostic value of acid phosphatase and lactate dehydrogenase of lymphocytes.", "contents": "[Enzymatic activity of the lymphocytes in gnotobionts in adenovirus infection]. The cytochemical activity of succinate dehydrogenases, alpha-glycerophosphate (mitochondrial and hyaloplasmic), lactate, glycose-6-phosphate, glutamate, beta-oxibutyrate, NADP-H2- and NAD-H2 diaphorases and acid phosphatase was studied in lymphocytes of gnotobiotic guinea-pigs infected with human adenovirus type 1. The analysis of transgression of distribution of the values in the experimental and control groups revealed a high informative diagnostic value of acid phosphatase and lactate dehydrogenase of lymphocytes."}
{"id": "PMID:208308", "title": "[Use of the monkey pox virus for evaluating the intensity of the immunity against smallpox in experiments on M. rhesus].", "content": "Monkeypox virus causing in M, rhesus upon aerogenic infection a disease similar to human varioloid was used to evaluate the intensity of immunity against smallpox in immunized M. rhesus monkeys. Postvaccination immunity was solid in all the animals vaccinated intradermally or orally. In 2 out of 14 monkeys immunized orally, however, the immunity was partially overcome. Neutralizing antibody titers in these two monkeys were 1:5 and 1:25, respectively. This agreed with the observations made in Pakistan indicating the possibility that some humans having serum neutralizing antibody titers up to 1:32 could contract smallpox and develop the disease.", "contents": "[Use of the monkey pox virus for evaluating the intensity of the immunity against smallpox in experiments on M. rhesus]. Monkeypox virus causing in M, rhesus upon aerogenic infection a disease similar to human varioloid was used to evaluate the intensity of immunity against smallpox in immunized M. rhesus monkeys. Postvaccination immunity was solid in all the animals vaccinated intradermally or orally. In 2 out of 14 monkeys immunized orally, however, the immunity was partially overcome. Neutralizing antibody titers in these two monkeys were 1:5 and 1:25, respectively. This agreed with the observations made in Pakistan indicating the possibility that some humans having serum neutralizing antibody titers up to 1:32 could contract smallpox and develop the disease."}
{"id": "PMID:208306", "title": "[Effect of inactivated Sendai virus on polyomavirus adsorption and penetration].", "content": "The quantitative study of adsorption, elution, and penetration of oncogenic polyoma virus (PV) labeled with 3H-thymidine under the influence of beta-propiolactone-inactivated Sendai virus (SV) was carried out in a permissive culture of mouse embryo fibroblasts and in two nonpermissive cultures of human embryo and chick embryo fibroblasts. In adsorption of PV on permissive and nonpermissive cells SV was found to reduce the amount of the adsorbed virus if used before the adsorption and to have no effect on adsorption upon reverse order of treatment of the cells with the two viruses. SV facilitates elution with 5 mM EDTA of PV adsorbed on both permissive and nonpermissive cells. Under the influence of SV, PV could be eluted from the surface of the permissive cells within 1 hour after adsorption and from the surface of the nonpermissive cells within 5-6 hours. Three hours after PV adsorption on permissive cells, both treated and untreated with SV, most of PV DNA (approximately 60%) was found in the nuclear fraction. At the same time, in the nuclear fraction of nonpermissive cells, treated or untreated with SV, the amount of PV DNA was insignificant (about 13%). The fraction containing large granules isolated from the cells which had been in contact with SV was found to contain approximately 50% of 3H-thymidine label.", "contents": "[Effect of inactivated Sendai virus on polyomavirus adsorption and penetration]. The quantitative study of adsorption, elution, and penetration of oncogenic polyoma virus (PV) labeled with 3H-thymidine under the influence of beta-propiolactone-inactivated Sendai virus (SV) was carried out in a permissive culture of mouse embryo fibroblasts and in two nonpermissive cultures of human embryo and chick embryo fibroblasts. In adsorption of PV on permissive and nonpermissive cells SV was found to reduce the amount of the adsorbed virus if used before the adsorption and to have no effect on adsorption upon reverse order of treatment of the cells with the two viruses. SV facilitates elution with 5 mM EDTA of PV adsorbed on both permissive and nonpermissive cells. Under the influence of SV, PV could be eluted from the surface of the permissive cells within 1 hour after adsorption and from the surface of the nonpermissive cells within 5-6 hours. Three hours after PV adsorption on permissive cells, both treated and untreated with SV, most of PV DNA (approximately 60%) was found in the nuclear fraction. At the same time, in the nuclear fraction of nonpermissive cells, treated or untreated with SV, the amount of PV DNA was insignificant (about 13%). The fraction containing large granules isolated from the cells which had been in contact with SV was found to contain approximately 50% of 3H-thymidine label."}
{"id": "PMID:208315", "title": "[Cryotherapy of the cylindroma syndrome].", "content": "Two patients with dermal Cylindromas were successfully treated with a special cryoapplicator. This small cryosurgical unit consists of a copper core of 645 g with a 1,5 cm insulating styropore body. At the one end, the cylindrical core has a projection bearing the therapeutic surface, at the other a thread, which takes up a manipulator. This serves the purpose of transfering the core into liquid gas and, after throughout cooling, into the styropore body. After half an hour of therapeutic use, the warmed core requires new cooling in liquid nitrogen or liquid air.", "contents": "[Cryotherapy of the cylindroma syndrome]. Two patients with dermal Cylindromas were successfully treated with a special cryoapplicator. This small cryosurgical unit consists of a copper core of 645 g with a 1,5 cm insulating styropore body. At the one end, the cylindrical core has a projection bearing the therapeutic surface, at the other a thread, which takes up a manipulator. This serves the purpose of transfering the core into liquid gas and, after throughout cooling, into the styropore body. After half an hour of therapeutic use, the warmed core requires new cooling in liquid nitrogen or liquid air."}
{"id": "PMID:208309", "title": "[Rapid diagnosis of infections caused by the chickenpox-herpes zoster viruses].", "content": "A diagnostic preparation for the indirect hemagglutination test (IHA) was obtained by sensitization of fixed tannin-treated sheep erythrocytes with IgG-fractions from human herpes zoster convalescent sera. A high specificity of the preparation was established in comparative experiments. It could detect the varicella-herpes-zoster virus antigen in 100% of specimens from patients. The IHA test with this erythrocyte diagnostic preparation is simple, economic, gives the results within 1-1 1/2 hours after the specimens arrive in the laboratory. A great advantage of this test ipesviruses.", "contents": "[Rapid diagnosis of infections caused by the chickenpox-herpes zoster viruses]. A diagnostic preparation for the indirect hemagglutination test (IHA) was obtained by sensitization of fixed tannin-treated sheep erythrocytes with IgG-fractions from human herpes zoster convalescent sera. A high specificity of the preparation was established in comparative experiments. It could detect the varicella-herpes-zoster virus antigen in 100% of specimens from patients. The IHA test with this erythrocyte diagnostic preparation is simple, economic, gives the results within 1-1 1/2 hours after the specimens arrive in the laboratory. A great advantage of this test ipesviruses."}
{"id": "PMID:208317", "title": "Uptake of polynucleotides by mammalian cells. XV. Properties and function of a DNA-protein complex situated in the outer membrane of Ehrlich ascites tumor cells.", "content": "1) DNA-protein complexes are supposed to be original constituents of the membrane of Ehrlich ascites tumor cells. These complexes can be attacked at the surface of viable cells by DNase or protease. The DNA is partially embedded in protein structures. 2) The net charge of this complex is of major importance for the RNA uptake capacity of the cells. Negatively charged DNA which is situated at the surface hinders RNA uptake. This is the explanation for the stimulation of RNA uptake by DNase or the decrease in RNA uptake after protease treatment. 3) Upon treatment of DNA-deficient complexes with homologous or heterologous DNA the original RNA uptake capacity of the cells is restored but the original conformation of the complex cannot be regained. 4) The DNase action on the complex is temperature dependent in a sigmoidal fashion. It is markedly slowed down at temperatures below 12 degrees C. This implies that structural changes in the complex occur at this transition temperature which make surface DNA susceptible to DNase. This effect can only be observed in original structures but not in reconstituted ones. 5) Polyanion treatment of the cells [poly(L-lysine)] which increases their RNA uptake capacity, most probably does not interact with the DNA-protein complex. Poly(L-lysine) appears to act at other membrane sites. 6) The DNA-protein complex has been investigated entirely in situ, i.e. situated in the membrane of viable cells.", "contents": "Uptake of polynucleotides by mammalian cells. XV. Properties and function of a DNA-protein complex situated in the outer membrane of Ehrlich ascites tumor cells. 1) DNA-protein complexes are supposed to be original constituents of the membrane of Ehrlich ascites tumor cells. These complexes can be attacked at the surface of viable cells by DNase or protease. The DNA is partially embedded in protein structures. 2) The net charge of this complex is of major importance for the RNA uptake capacity of the cells. Negatively charged DNA which is situated at the surface hinders RNA uptake. This is the explanation for the stimulation of RNA uptake by DNase or the decrease in RNA uptake after protease treatment. 3) Upon treatment of DNA-deficient complexes with homologous or heterologous DNA the original RNA uptake capacity of the cells is restored but the original conformation of the complex cannot be regained. 4) The DNase action on the complex is temperature dependent in a sigmoidal fashion. It is markedly slowed down at temperatures below 12 degrees C. This implies that structural changes in the complex occur at this transition temperature which make surface DNA susceptible to DNase. This effect can only be observed in original structures but not in reconstituted ones. 5) Polyanion treatment of the cells [poly(L-lysine)] which increases their RNA uptake capacity, most probably does not interact with the DNA-protein complex. Poly(L-lysine) appears to act at other membrane sites. 6) The DNA-protein complex has been investigated entirely in situ, i.e. situated in the membrane of viable cells."}
{"id": "PMID:208318", "title": "Further investigations on the p-nitrophenylphosphatase activity of intact Ehrlich ascites tumor cells.", "content": "The substrate specificity and the effects of nucleotides and SH-blocking agents on the p-nitrophenylphosphatase activity of intact Ehrlich ascites tumor cells (EAT) cells were studied. DL-beta-Glycerophosphate, o-phosphoethanolamine, cholinephosphate, glucose-6-phosphate, o-carboxyphenylphosphate,, phosphoenolpyruvate and AMP were not attacked by intact cells. ATP is greater than GTP is greater than UPT is greater than PPi is greater than pNPP were cleaved with decreasing velocity. A stimulation of the cleavage of p-NPP by the following nucleotides was observed with decreasing effectivity: ATP is greater than ADP is greater than GTP is greater than UTP; AMP was ineffective. The phosphatase activity was not affected by malate, tartrate and glutathion disulfide. The SH blocking agents diamide and thimerosal were more effective inhibitors of the pNPPase than of the ATPase activity, whereas the hydrolysis of ATP is more affected by the ATP analog adenylylimidodiphosphate. The present data are best compatible with a double headed enzyme: Both active sites interact with ATP, only one is active against p-NPP and sensitive against SH-blocking agents.", "contents": "Further investigations on the p-nitrophenylphosphatase activity of intact Ehrlich ascites tumor cells. The substrate specificity and the effects of nucleotides and SH-blocking agents on the p-nitrophenylphosphatase activity of intact Ehrlich ascites tumor cells (EAT) cells were studied. DL-beta-Glycerophosphate, o-phosphoethanolamine, cholinephosphate, glucose-6-phosphate, o-carboxyphenylphosphate,, phosphoenolpyruvate and AMP were not attacked by intact cells. ATP is greater than GTP is greater than UPT is greater than PPi is greater than pNPP were cleaved with decreasing velocity. A stimulation of the cleavage of p-NPP by the following nucleotides was observed with decreasing effectivity: ATP is greater than ADP is greater than GTP is greater than UTP; AMP was ineffective. The phosphatase activity was not affected by malate, tartrate and glutathion disulfide. The SH blocking agents diamide and thimerosal were more effective inhibitors of the pNPPase than of the ATPase activity, whereas the hydrolysis of ATP is more affected by the ATP analog adenylylimidodiphosphate. The present data are best compatible with a double headed enzyme: Both active sites interact with ATP, only one is active against p-NPP and sensitive against SH-blocking agents."}
{"id": "PMID:208325", "title": "[Urogenital tuberculosis within the scope of general tuberculosis situation. Ambulatory management and care].", "content": "On the basis of two differential graphs the development of the general situation concerning tuberculosis in the GDR for the years 1962 to 1976 is described. Particularly taken into consideration were the new cases of urogenital tuberculosis which were compared with the rates of new cases in other countries. A significantly higher morbidity of tuberculosis was found in members of certain risk groups (so-called \"gesunde Befundtr\u00e4ger\" [healthy persons not yet suffering from tuberculosis]). Regulations of the law for prevention of and combat against tuberculosis, principles of the continued ambulant treatment and the importance of the dispensary care were discussed. The success of treatment in the Berlin district, especially in the combat against urogenital tuberculosis, which refer to a more than 12 years observation period, are traced back to a continuity of initial stay in an urological clinic in connection with special procedures, following continued ambulant treatment and final after-care.", "contents": "[Urogenital tuberculosis within the scope of general tuberculosis situation. Ambulatory management and care]. On the basis of two differential graphs the development of the general situation concerning tuberculosis in the GDR for the years 1962 to 1976 is described. Particularly taken into consideration were the new cases of urogenital tuberculosis which were compared with the rates of new cases in other countries. A significantly higher morbidity of tuberculosis was found in members of certain risk groups (so-called \"gesunde Befundtr\u00e4ger\" [healthy persons not yet suffering from tuberculosis]). Regulations of the law for prevention of and combat against tuberculosis, principles of the continued ambulant treatment and the importance of the dispensary care were discussed. The success of treatment in the Berlin district, especially in the combat against urogenital tuberculosis, which refer to a more than 12 years observation period, are traced back to a continuity of initial stay in an urological clinic in connection with special procedures, following continued ambulant treatment and final after-care."}
{"id": "PMID:208326", "title": "Grave cranio-cerebral trauma 30 years ago as cause of the brain glioma at the locus of the trauma particulars of the case.", "content": "A glioblastoma multiforma developed 30 years after a penetrating craniocerebral injury in the left parietal region caused by fragments of an artillery projectile. The 3 cm large bone defect was located directly above the tumour. There were close scarry connections between dura, brain and tumour. Partial removal could not prevent the lethal exitus. Causal connection with the accident is assumed to exist.", "contents": "Grave cranio-cerebral trauma 30 years ago as cause of the brain glioma at the locus of the trauma particulars of the case. A glioblastoma multiforma developed 30 years after a penetrating craniocerebral injury in the left parietal region caused by fragments of an artillery projectile. The 3 cm large bone defect was located directly above the tumour. There were close scarry connections between dura, brain and tumour. Partial removal could not prevent the lethal exitus. Causal connection with the accident is assumed to exist."}
{"id": "PMID:208328", "title": "[Rational method of obtaining sera with a high titre of virus-neutralizing antibodies. Report 2].", "content": "In addition to report I (ZHMEI, 1977, No. 1) a study was made of 9 more schemes of rabbit immunization with the poliomyelitis virus, type I, for the purpose of obtaining the neutralizing sera of high titre. Vitamins A and C were used in the experiments in the capacity of the activators of the organism reaction; Freund's adjuvant of different make was tested; different reimmunization periods and different amounts of the adjuvant were administered. Titration of rabbit sera in the process of immunization and reimmunization showed immunization into the lymph nodes with the subsequent single reimmunization in one month to be the most effective and economical method of obtaining high effective sera.", "contents": "[Rational method of obtaining sera with a high titre of virus-neutralizing antibodies. Report 2]. In addition to report I (ZHMEI, 1977, No. 1) a study was made of 9 more schemes of rabbit immunization with the poliomyelitis virus, type I, for the purpose of obtaining the neutralizing sera of high titre. Vitamins A and C were used in the experiments in the capacity of the activators of the organism reaction; Freund's adjuvant of different make was tested; different reimmunization periods and different amounts of the adjuvant were administered. Titration of rabbit sera in the process of immunization and reimmunization showed immunization into the lymph nodes with the subsequent single reimmunization in one month to be the most effective and economical method of obtaining high effective sera."}
{"id": "PMID:208329", "title": "[Protoplast fragmentation as one of the possible mechanisms of L-transformation of bacteria (Clostridium perfringens)].", "content": "As revealed, the action of lysozyme on the cells of Clostridium perfringens BP-6K led to the formation of not only typical spheroplasts, but also of cells whose peripheral parts of the cytoplasm were fragmented by membrane component. Small bodies framed by the membrane proper and containing granular and fibrillar components were formed. They were polymorphic in osmium treatment, and had smooth contours in preliminary use of aldehyde fixation. In the latter case a dense lumpy material analogous to the one which fills the periplasmic zone and serves as a rigid wall component formed at the surface of the protoplasm and bodies-fragments. In case of escape of the bodies into the external environment through the perforations in the cell wall the principal mass of the protoplast remains intact. The morphology of the bodies-fragments indicated a principal possibility of their autonomic existence. It is supposed that the phenomenon described could serve as one of the mechanisms of L-cell formation.", "contents": "[Protoplast fragmentation as one of the possible mechanisms of L-transformation of bacteria (Clostridium perfringens)]. As revealed, the action of lysozyme on the cells of Clostridium perfringens BP-6K led to the formation of not only typical spheroplasts, but also of cells whose peripheral parts of the cytoplasm were fragmented by membrane component. Small bodies framed by the membrane proper and containing granular and fibrillar components were formed. They were polymorphic in osmium treatment, and had smooth contours in preliminary use of aldehyde fixation. In the latter case a dense lumpy material analogous to the one which fills the periplasmic zone and serves as a rigid wall component formed at the surface of the protoplasm and bodies-fragments. In case of escape of the bodies into the external environment through the perforations in the cell wall the principal mass of the protoplast remains intact. The morphology of the bodies-fragments indicated a principal possibility of their autonomic existence. It is supposed that the phenomenon described could serve as one of the mechanisms of L-cell formation."}
{"id": "PMID:208330", "title": "[Homogeneous Cl. perfringens alpha-anatoxin: its physicochemical and immunogenic properties].", "content": "The authors present a method of obtaining relatively homogeneous preparations of alpha-toxoid of Cl. perfringens, type A, including the primary conception of the alpha-toxin proteins, their chromatography on DEAE-cellulose, fractionation with (NH4)2SO4, detoxication, with the subsequent gel-filtration through sephadex and isoelectric focussing. Sedimentation coefficient of the preparation proved to be 3.8 S, isoelectric point-4.83 +/- 0.07. In studying the immunogenic properties of alpha-toxoid in experiments on guinea pigs and rabbits their high immunogenicity, exceeding that of the industrial toxoid 8- and 6-fold, respectively, was established. Homogeneous preparations of alpha-toxoid provided intense anti-microbial immunity. Interlinear differences in the levels of the immune response of inbred mice, highly-reactive (BALB/c) and low-reactive (C57BL/6) to alpha-toxoid, reached 20-fold; in combination with the high immunogenicity of this antigen for mice this permits to recommend it for immunogenic studies.", "contents": "[Homogeneous Cl. perfringens alpha-anatoxin: its physicochemical and immunogenic properties]. The authors present a method of obtaining relatively homogeneous preparations of alpha-toxoid of Cl. perfringens, type A, including the primary conception of the alpha-toxin proteins, their chromatography on DEAE-cellulose, fractionation with (NH4)2SO4, detoxication, with the subsequent gel-filtration through sephadex and isoelectric focussing. Sedimentation coefficient of the preparation proved to be 3.8 S, isoelectric point-4.83 +/- 0.07. In studying the immunogenic properties of alpha-toxoid in experiments on guinea pigs and rabbits their high immunogenicity, exceeding that of the industrial toxoid 8- and 6-fold, respectively, was established. Homogeneous preparations of alpha-toxoid provided intense anti-microbial immunity. Interlinear differences in the levels of the immune response of inbred mice, highly-reactive (BALB/c) and low-reactive (C57BL/6) to alpha-toxoid, reached 20-fold; in combination with the high immunogenicity of this antigen for mice this permits to recommend it for immunogenic studies."}
{"id": "PMID:208327", "title": "[Comparative study of phospholipids in the neurons and glial cells of the brains of mammals, birds and reptiles].", "content": "Studies have been made on total content of phospholipids and relative content of various phospholipid families in neuronal and glial fractions obtained from the brain cortex of albino rat and brain hemispheres of the pigeon Columba livia and tortoise Testudo horsfieldi, as well as in oligodendroglial fraction of centrum semiovale and corpus callosum of the brain of rabbits. It was shown that in all the animals studied, the total glial fraction is approximately twice as rich in phospholipids as the neuronal one. With respect to the quantity of phospholipids, glial fraction is similar to the homogenate. Relative content of various phospholipid families in the homogenate and the cellular fractions is approximately identical. Yet, some differences were found between various fractions, as well as between the homologous fractions obtained from representatives of different classes. In all animals investigated, the neuronal fraction exhibits higher phosphatydylinositol content than the glial one. Pigeon neurons have higher level of phosphatydylinositol and lower level of phosphatydyl serine, as compared to rat and tortoise neurons. Glial fraction of rats contains significantly less sphingomyelin, than that of pigeons and tortoises. With respect to phospholipid composition, oligodendroglial fraction differs from total glial one and from neuronal fraction, being also different from the myelin.", "contents": "[Comparative study of phospholipids in the neurons and glial cells of the brains of mammals, birds and reptiles]. Studies have been made on total content of phospholipids and relative content of various phospholipid families in neuronal and glial fractions obtained from the brain cortex of albino rat and brain hemispheres of the pigeon Columba livia and tortoise Testudo horsfieldi, as well as in oligodendroglial fraction of centrum semiovale and corpus callosum of the brain of rabbits. It was shown that in all the animals studied, the total glial fraction is approximately twice as rich in phospholipids as the neuronal one. With respect to the quantity of phospholipids, glial fraction is similar to the homogenate. Relative content of various phospholipid families in the homogenate and the cellular fractions is approximately identical. Yet, some differences were found between various fractions, as well as between the homologous fractions obtained from representatives of different classes. In all animals investigated, the neuronal fraction exhibits higher phosphatydylinositol content than the glial one. Pigeon neurons have higher level of phosphatydylinositol and lower level of phosphatydyl serine, as compared to rat and tortoise neurons. Glial fraction of rats contains significantly less sphingomyelin, than that of pigeons and tortoises. With respect to phospholipid composition, oligodendroglial fraction differs from total glial one and from neuronal fraction, being also different from the myelin."}
{"id": "PMID:208332", "title": "[Cyclic 3--5-adenosine monophosphate metabolism in patients with Duchenne myodystrophy].", "content": "The state of metabolism of cyclic adenosinmonophosphate was studied. It was established that the concentration of nucleotides was distinctly lower in patients with this disease. The activity of adenilacyclose did not differ from normal rates. The enzyme to a large degree lost its capability of reacting to hormones, which made the metabolism in tissues to a certain extent autonomous. These data permit to rise the question of conducting a correcting treatment. In other forms of progressive muscular dystrophy the level of cyclic adenosinmonophosphate did not differ significantly from normal indices.", "contents": "[Cyclic 3--5-adenosine monophosphate metabolism in patients with Duchenne myodystrophy]. The state of metabolism of cyclic adenosinmonophosphate was studied. It was established that the concentration of nucleotides was distinctly lower in patients with this disease. The activity of adenilacyclose did not differ from normal rates. The enzyme to a large degree lost its capability of reacting to hormones, which made the metabolism in tissues to a certain extent autonomous. These data permit to rise the question of conducting a correcting treatment. In other forms of progressive muscular dystrophy the level of cyclic adenosinmonophosphate did not differ significantly from normal indices."}
{"id": "PMID:208333", "title": "Hormonal activation of adenylate cyclase and its role in cyclic AMP mediated regulation of RNA synthesis in the mouse mammary gland.", "content": "The activity of adenylate cyclase (EC 4.6.1.1) in the mouse mammary gland increases during late pregnancy and reaches its maximum value at one day pre partum. In the mouse mammary gland explant culture the adenylate cyclase activity is stimulated by a cooperative action of insulin, prolactin and hydrocortisone. The effect of these hormones can be demonstrated in intact cells, but not in a cell-free system. In the explants, RNA synthesis is stimulated by dibutyryl cyclic AMP, insulin and prolactin. The effects of both protein hormones and cyclic AMP are additive. The results obtained suggest that insulin and prolactin in cooperation with hydrocortisone are involved in the regulation of RNA synthesis in the mammary gland by activation of the adenylate cyclase system, independently of their effect on this process not mediated by cyclic AMP.", "contents": "Hormonal activation of adenylate cyclase and its role in cyclic AMP mediated regulation of RNA synthesis in the mouse mammary gland. The activity of adenylate cyclase (EC 4.6.1.1) in the mouse mammary gland increases during late pregnancy and reaches its maximum value at one day pre partum. In the mouse mammary gland explant culture the adenylate cyclase activity is stimulated by a cooperative action of insulin, prolactin and hydrocortisone. The effect of these hormones can be demonstrated in intact cells, but not in a cell-free system. In the explants, RNA synthesis is stimulated by dibutyryl cyclic AMP, insulin and prolactin. The effects of both protein hormones and cyclic AMP are additive. The results obtained suggest that insulin and prolactin in cooperation with hydrocortisone are involved in the regulation of RNA synthesis in the mammary gland by activation of the adenylate cyclase system, independently of their effect on this process not mediated by cyclic AMP."}
{"id": "PMID:208334", "title": "Disappearance of the cyanide-insensitive pathway of oxidation in mitochondria of MI-1 mutant of Neurospora crassa in vitro.", "content": "Oxidation of exogenous NADH in mitochondria isolated from wild type and mi-1 mutant of Neurospora crassa decreases rapidly in vitro. In mi-1 mutant mitochondria the inactivation concerns the alternate pathway of oxidation whereas in the wild type it involves an unknown component of the respiratory chain. The activity of the primary NADH dehydrogenase is constant within the time of the experiments (2-4 h). NADH oxidase is not inactivated if oxygen is removed from the incubation medium by nitrogen bubbling. Succinate oxidase does not show any remarkable changes in activity within 2-3 h. In fresh mitochondria of the mi-1 mutant reduced ubiquinone is completely reoxidized by cytochrome oxidase but only 80% reoxidized by the alternate oxidase. In aged mitochondria of the mi-1 mutant in the presence of cyanide, ubiquinone is reduced to the level characteristic for fresh mitochondria in which respiration is completely inhibited by cyanide plus salicylhydroxamic acid. In these mitochondria the reoxidation of the reduced ubiquinone proceeds only via the cytochrome pathway. It is supposed that a labile component(s) of the respiratory chain present in the mi-1 mutant and the wild type mitochondria may, in mi-1 mutant, act as an alternate oxidase.", "contents": "Disappearance of the cyanide-insensitive pathway of oxidation in mitochondria of MI-1 mutant of Neurospora crassa in vitro. Oxidation of exogenous NADH in mitochondria isolated from wild type and mi-1 mutant of Neurospora crassa decreases rapidly in vitro. In mi-1 mutant mitochondria the inactivation concerns the alternate pathway of oxidation whereas in the wild type it involves an unknown component of the respiratory chain. The activity of the primary NADH dehydrogenase is constant within the time of the experiments (2-4 h). NADH oxidase is not inactivated if oxygen is removed from the incubation medium by nitrogen bubbling. Succinate oxidase does not show any remarkable changes in activity within 2-3 h. In fresh mitochondria of the mi-1 mutant reduced ubiquinone is completely reoxidized by cytochrome oxidase but only 80% reoxidized by the alternate oxidase. In aged mitochondria of the mi-1 mutant in the presence of cyanide, ubiquinone is reduced to the level characteristic for fresh mitochondria in which respiration is completely inhibited by cyanide plus salicylhydroxamic acid. In these mitochondria the reoxidation of the reduced ubiquinone proceeds only via the cytochrome pathway. It is supposed that a labile component(s) of the respiratory chain present in the mi-1 mutant and the wild type mitochondria may, in mi-1 mutant, act as an alternate oxidase."}
{"id": "PMID:208335", "title": "Alpha- and beta-adrenergic receptor stimulation in cultures of beating rat heart cells and its effect on automaticity and cyclic AMP levels.", "content": "Positive chronotropic responses were elicited in rocker cultures of beating ventricle cells of 1 to 4-day old rats by both alpha- and beta-adrenergic receptor stimulation. Only the beta and not the alpha-adrenergic receptor-mediated increase in automaticity was associated with a rise in the level of cyclic AMP in the cultures.", "contents": "Alpha- and beta-adrenergic receptor stimulation in cultures of beating rat heart cells and its effect on automaticity and cyclic AMP levels. Positive chronotropic responses were elicited in rocker cultures of beating ventricle cells of 1 to 4-day old rats by both alpha- and beta-adrenergic receptor stimulation. Only the beta and not the alpha-adrenergic receptor-mediated increase in automaticity was associated with a rise in the level of cyclic AMP in the cultures."}
{"id": "PMID:208336", "title": "Brain acetylcholine, adenine nucleotides and their degradation products after intraperitoneal and intracerebral adenosine administration.", "content": "The paper describes adenosine effects on the acetylcholine synthesis and the profiles of adenine nucleotides, adenosine, inosine, and hypoxanthine in the rat brain in vivo after intracerebral (intraventricular) and intraperitoneal administration of adenosine. Intracerebral as well as extracerebral adenosine injection caused a dose- and time-dependent increase of the cerebral acetylcholine level, which was not accompanied by an equal development of the contents of adenine compounds and their degradation products. However, a considerable turnover of adenosine was observed in the brain after both routes of administration concerning the nucleotide as well as the degradation pathway. The kinetics of the purified enzymes of choline acetyltransferase and acetylcholinesterase were not influenced by adenosine. By this, the adenosine-caused increase of the cerebral acetylcholine cannot be explained by a direct molecular attack of adenosine on the enzymes of the synthesis or degradation of acetylcholine. An indirect mechanism which includes cAMP was discussed as a possible interpretation at present.", "contents": "Brain acetylcholine, adenine nucleotides and their degradation products after intraperitoneal and intracerebral adenosine administration. The paper describes adenosine effects on the acetylcholine synthesis and the profiles of adenine nucleotides, adenosine, inosine, and hypoxanthine in the rat brain in vivo after intracerebral (intraventricular) and intraperitoneal administration of adenosine. Intracerebral as well as extracerebral adenosine injection caused a dose- and time-dependent increase of the cerebral acetylcholine level, which was not accompanied by an equal development of the contents of adenine compounds and their degradation products. However, a considerable turnover of adenosine was observed in the brain after both routes of administration concerning the nucleotide as well as the degradation pathway. The kinetics of the purified enzymes of choline acetyltransferase and acetylcholinesterase were not influenced by adenosine. By this, the adenosine-caused increase of the cerebral acetylcholine cannot be explained by a direct molecular attack of adenosine on the enzymes of the synthesis or degradation of acetylcholine. An indirect mechanism which includes cAMP was discussed as a possible interpretation at present."}
{"id": "PMID:208337", "title": "[Inhibition of 3-H-noradrenalin uptake in synaptosomes by substance P].", "content": "The uptake kinetics of DL-[3H]-norepinephrine into synaptosomes from rat brain hypothalamus can be described as a two stage process with uptake constants of Km = 0.9 micron and Km = 0.06 micron, respectively. Substance P exerts an inhibiting influence on both uptakes. The possible importance of this inhibition for the regulation of noradrenergic transmission is discussed.", "contents": "[Inhibition of 3-H-noradrenalin uptake in synaptosomes by substance P]. The uptake kinetics of DL-[3H]-norepinephrine into synaptosomes from rat brain hypothalamus can be described as a two stage process with uptake constants of Km = 0.9 micron and Km = 0.06 micron, respectively. Substance P exerts an inhibiting influence on both uptakes. The possible importance of this inhibition for the regulation of noradrenergic transmission is discussed."}
{"id": "PMID:208340", "title": "Partial gonadotrophin-resistance in pseudohypoparathyroidism.", "content": "A patient with classical Albright's pseudohypoparathyroidism was investigated because of oligomenorrhoea. Hypo-oestrogenism was associated with elevated basal gonadotrophin values [mean basal serum LH and FSH were 272 +/- 84 (SD) ng/ml and 593 +/- 83 ng/ml, resplectively (normal less than or equal to 220 and less than or equal to 400, respectively)]. The response to gonadotrophin releasing hormone (Gn-RH) was exaggerated, with maximal LH and FSH increments of 1688 and 458 ng/ml, respectively. These results and the findings on ovarian biopsy were compatible with partial ovarian resistance to gonadotrophins. This resistance could be overcome by administration of human menopausal gonadotrophins. This is the first evidence for gonadotrophin resistance in pseudohypoparathyroidism. The plasma cyclic adenosine-3',5'-monophosphate response to glucagon administration by two different protocols was about 70% that of normal control subjects. Other endocrine glands whose responses to hormones are mediated via the adenylate cyclase system evidenced minor abnormalities of questionable significance. This indirect evidence is compatible with a more extensive defect in the adenylate cyclase system in pseudohypoparathyroidism than has hitherto been suspected.", "contents": "Partial gonadotrophin-resistance in pseudohypoparathyroidism. A patient with classical Albright's pseudohypoparathyroidism was investigated because of oligomenorrhoea. Hypo-oestrogenism was associated with elevated basal gonadotrophin values [mean basal serum LH and FSH were 272 +/- 84 (SD) ng/ml and 593 +/- 83 ng/ml, resplectively (normal less than or equal to 220 and less than or equal to 400, respectively)]. The response to gonadotrophin releasing hormone (Gn-RH) was exaggerated, with maximal LH and FSH increments of 1688 and 458 ng/ml, respectively. These results and the findings on ovarian biopsy were compatible with partial ovarian resistance to gonadotrophins. This resistance could be overcome by administration of human menopausal gonadotrophins. This is the first evidence for gonadotrophin resistance in pseudohypoparathyroidism. The plasma cyclic adenosine-3',5'-monophosphate response to glucagon administration by two different protocols was about 70% that of normal control subjects. Other endocrine glands whose responses to hormones are mediated via the adenylate cyclase system evidenced minor abnormalities of questionable significance. This indirect evidence is compatible with a more extensive defect in the adenylate cyclase system in pseudohypoparathyroidism than has hitherto been suspected."}
{"id": "PMID:208341", "title": "In vitro effects of theophylline and aminogluthetimide upon basal and ACTH induced cAMP levels and steroid output by the normal human adrenal gland.", "content": "The in vitro effects of theophylline and aminogluthetimide upon basal and ACTH stimulated cAMP, cortisol and aldosterone responses of normal human adrenocortical tissue were evaluated. Theophylline increased basal cAMP levels and cortisol output, however, basal aldosterone output was depressed. Theophylline in concert with ACTH depressed cortisol and aldosterone output. Aminogluthetimide alone did not affect basal cAMP levels, however, the normal cAMP response to ACTH was delayed in aminogluthetimide pre-treated adrenals. Aminogluthetimide also depressed basal and ACTH stimulated cortisol and aldosterone output with the latter being more sensitive. The findings indicate that both theophylline and aminogluthetimide produce effects upon the adrenal in addition to inhibition of phosphodiesterase and cholesterol side-chain cleavage, respectively. Further, theophylline depression of ACTH stimulated steroid output may be helpful in understanding the interplay between a number of factors in the control of adrenal steroid biosynthesis and release.", "contents": "In vitro effects of theophylline and aminogluthetimide upon basal and ACTH induced cAMP levels and steroid output by the normal human adrenal gland. The in vitro effects of theophylline and aminogluthetimide upon basal and ACTH stimulated cAMP, cortisol and aldosterone responses of normal human adrenocortical tissue were evaluated. Theophylline increased basal cAMP levels and cortisol output, however, basal aldosterone output was depressed. Theophylline in concert with ACTH depressed cortisol and aldosterone output. Aminogluthetimide alone did not affect basal cAMP levels, however, the normal cAMP response to ACTH was delayed in aminogluthetimide pre-treated adrenals. Aminogluthetimide also depressed basal and ACTH stimulated cortisol and aldosterone output with the latter being more sensitive. The findings indicate that both theophylline and aminogluthetimide produce effects upon the adrenal in addition to inhibition of phosphodiesterase and cholesterol side-chain cleavage, respectively. Further, theophylline depression of ACTH stimulated steroid output may be helpful in understanding the interplay between a number of factors in the control of adrenal steroid biosynthesis and release."}
{"id": "PMID:208345", "title": "Coincidence of dystrophia myotonica and pleomorphic adenoma of the parotid gland.", "content": "Two patients with dystrophia myotonica and pleomorphic adenoma of the parotid gland are described. The probability that this coincidence could be due to chance is less than 1 to 1,000 (P less than or equal to 0.001). There are several reports in the literature of the association of myotonic dystrophy with neoplasia. The reason for their association is not understood.", "contents": "Coincidence of dystrophia myotonica and pleomorphic adenoma of the parotid gland. Two patients with dystrophia myotonica and pleomorphic adenoma of the parotid gland are described. The probability that this coincidence could be due to chance is less than 1 to 1,000 (P less than or equal to 0.001). There are several reports in the literature of the association of myotonic dystrophy with neoplasia. The reason for their association is not understood."}
{"id": "PMID:208346", "title": "Syndrome of Dejerine's Fourth Reich.", "content": "Dejerine's (1914) precise description of the human corticobulbar tracts is now doubted and forgotten for want of clinical significance. He described them as five bundles of aberrant pyramidal fibres which separate out as leashes from the corticospinal fibres at different levels and each had its territory of bulbar nuclei (like the Reich which is the territory of the German empire of which there were only three). Five cases are described who presented with uppermotor neurone lesion of the 7th, 10th and 12th cranial nerves without evidence of involveement of the pyramidal fibres to the limbs. It is postulated that this is caused by a lesion of the 4th Reich described by Dejerine.", "contents": "Syndrome of Dejerine's Fourth Reich. Dejerine's (1914) precise description of the human corticobulbar tracts is now doubted and forgotten for want of clinical significance. He described them as five bundles of aberrant pyramidal fibres which separate out as leashes from the corticospinal fibres at different levels and each had its territory of bulbar nuclei (like the Reich which is the territory of the German empire of which there were only three). Five cases are described who presented with uppermotor neurone lesion of the 7th, 10th and 12th cranial nerves without evidence of involveement of the pyramidal fibres to the limbs. It is postulated that this is caused by a lesion of the 4th Reich described by Dejerine."}
{"id": "PMID:208347", "title": "Cryptophthalmos, dyscephaly, syndactyly and renal aplasia. Report of a case.", "content": "A danish girl with incomplete, bilateral cryptophalmos together with assoicated craniofacial malformations, laryngeal hypoplasia, syndactyly, unilateral renal aplasia and slight external genital abnormalities is reported. Chromosomal abnormalities or metabolic disorders were not demonstrated. As the condition is extremely rare, some clinical and pathological fingings previosuly described in analogous cases are mentioned, together with a few pathogenetic mechanisms. Finally, a discussion regarding the aetiology of the condition is presented. Most authors are convinced that the malformative pattern is a syndrome with an autosomally recessive genetic basis. Added envronmental influence explains the wide range of manifestations and the varying gene expressivity.", "contents": "Cryptophthalmos, dyscephaly, syndactyly and renal aplasia. Report of a case. A danish girl with incomplete, bilateral cryptophalmos together with assoicated craniofacial malformations, laryngeal hypoplasia, syndactyly, unilateral renal aplasia and slight external genital abnormalities is reported. Chromosomal abnormalities or metabolic disorders were not demonstrated. As the condition is extremely rare, some clinical and pathological fingings previosuly described in analogous cases are mentioned, together with a few pathogenetic mechanisms. Finally, a discussion regarding the aetiology of the condition is presented. Most authors are convinced that the malformative pattern is a syndrome with an autosomally recessive genetic basis. Added envronmental influence explains the wide range of manifestations and the varying gene expressivity."}
{"id": "PMID:208343", "title": "[Intracellular cAMP concentration in isolated cells of white blood cell series of peripheral blood and bone marrow in healthy subjects and patients with different proliferative syndromes].", "content": "The level of cAMP was determined in isolated cells from bone marrow and peripheral blood of healthy subjects and patients with proliferative syndrome (acute and chronic myeloid leukaemia and chronic lymphatic leukaemia). In the investigations tritiated cAMP (3H-cAMP) was used and for binding of endogenous as well as exogenous cAMP protein isolated from bovine muscles was used. The mean cAMP level in peripheral blood granulocytes of healthy subjects was 27.90+/-3.82 pmol/10(7) cells and in normal lymphocytes it was from 11 to 18 pmol/10(7) cells. Much higher concentrations of cAMP: 56.4+/-16.25 and 52.7+/-11.02 pmol/10(7) cells were observed in myelocytes and metamyelocytes isolated from the bone marrow of healthy subjects. Lowering of cAMP concentration (below 4 pmol/10(7) cells) was observed in the lymphocytes of patients with chronic lymphatic leukaemia, while a higher cAMP concentration (above 90 pmol/10(7) cells) was found in the myeloblasts of patients with acute myeloid leukaemia.", "contents": "[Intracellular cAMP concentration in isolated cells of white blood cell series of peripheral blood and bone marrow in healthy subjects and patients with different proliferative syndromes]. The level of cAMP was determined in isolated cells from bone marrow and peripheral blood of healthy subjects and patients with proliferative syndrome (acute and chronic myeloid leukaemia and chronic lymphatic leukaemia). In the investigations tritiated cAMP (3H-cAMP) was used and for binding of endogenous as well as exogenous cAMP protein isolated from bovine muscles was used. The mean cAMP level in peripheral blood granulocytes of healthy subjects was 27.90+/-3.82 pmol/10(7) cells and in normal lymphocytes it was from 11 to 18 pmol/10(7) cells. Much higher concentrations of cAMP: 56.4+/-16.25 and 52.7+/-11.02 pmol/10(7) cells were observed in myelocytes and metamyelocytes isolated from the bone marrow of healthy subjects. Lowering of cAMP concentration (below 4 pmol/10(7) cells) was observed in the lymphocytes of patients with chronic lymphatic leukaemia, while a higher cAMP concentration (above 90 pmol/10(7) cells) was found in the myeloblasts of patients with acute myeloid leukaemia."}
{"id": "PMID:208344", "title": "[Diffuse poliencephalitis and visceral neoplasm (author's transl)].", "content": "A case of diffuse polioencephalitis associated with non-differentiated bronchial carcinoma is reported. Clinically the patient presented mental distrubance and an extra-pyramidal syndrome. Anatomopathological investigation revealed inflammation of the cerebral hemispheres and the brain stem. Similar involvement of others regions of the central nervous system has been reported in the literature, probably indicating various locations of a single nosological entity. A viral origin is probable but not yet established.", "contents": "[Diffuse poliencephalitis and visceral neoplasm (author's transl)]. A case of diffuse polioencephalitis associated with non-differentiated bronchial carcinoma is reported. Clinically the patient presented mental distrubance and an extra-pyramidal syndrome. Anatomopathological investigation revealed inflammation of the cerebral hemispheres and the brain stem. Similar involvement of others regions of the central nervous system has been reported in the literature, probably indicating various locations of a single nosological entity. A viral origin is probable but not yet established."}
{"id": "PMID:208350", "title": "Histochemical and biochemical changes in human skeletal muscle with age in sedentary males, age 22--65 years.", "content": "Biopsies for histochemical and biochemical analyses were taken from the vastus lateralis muscle of 55 untrained, healthy male subjects from 22 to 65 years of age. Fibre type distribution changed towards a decrease in the percentage of type II fibres, both in type IIA and type IIB fibres, whereas type IIB/IIA fibre ratio and type IIC percentage did not change with increasing age. It was found that the type IIB/IIA fibre ratio was inversely related to type I fibres, i.e. subjects rich in type I fibres had a relatively smaller proportion of type IIB fibres. Fibre area determinations revealed a selective decrease in type II fibre area. Consequently, the type II/I fibre area ratio and relative type II fibre area decreased. No changes in the specific activities of Mg2+ stimulated ATPase and myokinase were observed, while the activity of lactate dehydrogenase (LDH) was higher in the youngest groups than in the oldest. LDH isozyme pattern shifted towards a decrease in percentage distribution of the muscle specific isozymes and a corresponding decrease in muscle specific activity while the activity of the heart specific isozymes did not change.", "contents": "Histochemical and biochemical changes in human skeletal muscle with age in sedentary males, age 22--65 years. Biopsies for histochemical and biochemical analyses were taken from the vastus lateralis muscle of 55 untrained, healthy male subjects from 22 to 65 years of age. Fibre type distribution changed towards a decrease in the percentage of type II fibres, both in type IIA and type IIB fibres, whereas type IIB/IIA fibre ratio and type IIC percentage did not change with increasing age. It was found that the type IIB/IIA fibre ratio was inversely related to type I fibres, i.e. subjects rich in type I fibres had a relatively smaller proportion of type IIB fibres. Fibre area determinations revealed a selective decrease in type II fibre area. Consequently, the type II/I fibre area ratio and relative type II fibre area decreased. No changes in the specific activities of Mg2+ stimulated ATPase and myokinase were observed, while the activity of lactate dehydrogenase (LDH) was higher in the youngest groups than in the oldest. LDH isozyme pattern shifted towards a decrease in percentage distribution of the muscle specific isozymes and a corresponding decrease in muscle specific activity while the activity of the heart specific isozymes did not change."}
{"id": "PMID:208351", "title": "Conversion of the electrophoretic pattern of type IV hyperlipidaemia to type III by intravenous heparin.", "content": "Heparin was given i.v. to subjects with type IV hyperlipoproteinaemia who had only ordinary pre-beta lipoproteins and no late pre-beta lipoproteins (LP-beta) in their very low density lipoproteins (VLDL, d less than 1.006) upon agarose gel lipoprotein electrophoresis. Within 15 min the electrophoretic pattern of VLDL had changed completely. The normal pre-beta lipoproteins had disappeared and a discrete LP-beta lipoprotein had appeared. This new electrophoretic pattern, induced 15 min after heparin, is similar to that diagnostic of type III hyperlipoproteinaemia. It is suggested that the LP-beta lipoproteins represent an end stage in the catabolism of VLDL.", "contents": "Conversion of the electrophoretic pattern of type IV hyperlipidaemia to type III by intravenous heparin. Heparin was given i.v. to subjects with type IV hyperlipoproteinaemia who had only ordinary pre-beta lipoproteins and no late pre-beta lipoproteins (LP-beta) in their very low density lipoproteins (VLDL, d less than 1.006) upon agarose gel lipoprotein electrophoresis. Within 15 min the electrophoretic pattern of VLDL had changed completely. The normal pre-beta lipoproteins had disappeared and a discrete LP-beta lipoprotein had appeared. This new electrophoretic pattern, induced 15 min after heparin, is similar to that diagnostic of type III hyperlipoproteinaemia. It is suggested that the LP-beta lipoproteins represent an end stage in the catabolism of VLDL."}
{"id": "PMID:208352", "title": "Myocardial scintigraphy with 99mTc-pyrophosphate in patients with unstable angina pectoris.", "content": "A total of 400 patients, aged 25-82 years, admitted to the Coronary Care Unit due to clinical suspicion of acute myocardial infarction, were examined with 10 mCi 99mTc labelled to pyrophosphate. The examinations were carried out 4-120 hours post onset of symptoms, with a mobile gamma camera. Scintigrams were evaluated with regard to presence, localization and intensity of an uptake. Among 249 patients with a verified acute myocardial infarction, uptake was found in 237. Sixty-two of 85 patients with unstable angina showed a diffuse uptake with low intensity. Scintigraphy could not be used as a prognostic index of which patients would later develop an infarct. However, the scintigraphic pattern was useful as an aid in the differential diagnosis between acute myocardial infarction and unstable angina.", "contents": "Myocardial scintigraphy with 99mTc-pyrophosphate in patients with unstable angina pectoris. A total of 400 patients, aged 25-82 years, admitted to the Coronary Care Unit due to clinical suspicion of acute myocardial infarction, were examined with 10 mCi 99mTc labelled to pyrophosphate. The examinations were carried out 4-120 hours post onset of symptoms, with a mobile gamma camera. Scintigrams were evaluated with regard to presence, localization and intensity of an uptake. Among 249 patients with a verified acute myocardial infarction, uptake was found in 237. Sixty-two of 85 patients with unstable angina showed a diffuse uptake with low intensity. Scintigraphy could not be used as a prognostic index of which patients would later develop an infarct. However, the scintigraphic pattern was useful as an aid in the differential diagnosis between acute myocardial infarction and unstable angina."}
{"id": "PMID:208353", "title": "The reliability of computer tomography for the diagnosis and differential diagnosis of meningiomas, gliomas, and brain metastases.", "content": "The CT characteristics were studied in a series of 90 tumours, and the diagnostic criteria were determined for meningiomas glioblastomas, other gliomas and metastases. These criteria were then employed in another group of 46 tumours in which the histological diagnosis was not known at the time of examination. The over-all diagnostic accuracy was 85%, and it was largely the same for the various sub-groups. Careful combination of the CT characteristics, perfect techniques, and increased experience may further improve the diagnostic accuracy.", "contents": "The reliability of computer tomography for the diagnosis and differential diagnosis of meningiomas, gliomas, and brain metastases. The CT characteristics were studied in a series of 90 tumours, and the diagnostic criteria were determined for meningiomas glioblastomas, other gliomas and metastases. These criteria were then employed in another group of 46 tumours in which the histological diagnosis was not known at the time of examination. The over-all diagnostic accuracy was 85%, and it was largely the same for the various sub-groups. Careful combination of the CT characteristics, perfect techniques, and increased experience may further improve the diagnostic accuracy."}
{"id": "PMID:208356", "title": "The effects of amphiphilic compounds on phosphatidate metabolism.", "content": "Amphiphilic cations interact with phosphatidate and thereby change its physical properties. This interaction can redirect phospholipid metabolism. In the presence of Mg2+ amphiphilic cations inhibit the activity of phosphatidate phosphohydrolase and stimulate that of phosphatidate cytidylyltransferase. Increasing the concentration of Mg2+ further, or adding Ca2+ have similar effects, except that Ca2+ does not stimulate phosphatidate cytidylyltransferase activity. Amphiphilic anions reverse the effects caused by the amphiphilic cations. The implication of these results are discussed in relation to the pharmacological effects of amphiphilic cationic drugs.", "contents": "The effects of amphiphilic compounds on phosphatidate metabolism. Amphiphilic cations interact with phosphatidate and thereby change its physical properties. This interaction can redirect phospholipid metabolism. In the presence of Mg2+ amphiphilic cations inhibit the activity of phosphatidate phosphohydrolase and stimulate that of phosphatidate cytidylyltransferase. Increasing the concentration of Mg2+ further, or adding Ca2+ have similar effects, except that Ca2+ does not stimulate phosphatidate cytidylyltransferase activity. Amphiphilic anions reverse the effects caused by the amphiphilic cations. The implication of these results are discussed in relation to the pharmacological effects of amphiphilic cationic drugs."}
{"id": "PMID:208359", "title": "Studies of rat brain choline ethanolamine phosphotransferases using labeled alkylacylglycerol as substrate with evidence for reversibility of the reactions.", "content": "Cholinephosphotransferase activity in brain microsomes may be assayed with labeled alkylacylglycerols or with CDP-choline with label in the phosphocholine with nearly identical results. The direct linear plot method was used for evaluation of Michaelis-Menten kinetic parameters. Most of the cholinephosphotransferase activity is in microsomes and a stimulatory factor seems to be present in the cytosol. Incubation of microsomes with labeled alkylacylglycerols and CDP-choline, in the initial absence of CDP-ethanolamine, produced labeled ethanolamine glycerophospholipids as well as labeled choline glycerophospholipids. Since the labeling of ethanolamine glycerophospholipids was increased by the addition of CMP, the labeling was probably due to the reversal of ethanolamine phosphotransferase to yield CDP-ethanolamine produced by the choline phosphotransferase reaction. Cholinephosphotransferase was reversed more readily than ethanolaminephosphotransferase in brain as it is in liver (Kanok and Ohno, 1973). Only trace quantities of plasmalogens were formed with labeled alkylacylglycerols. Previous results of plasmalogen labeling from labeled CDP-nucleotides were apparently due to reversal of phosphotransferase reactions. Alkylacylglycerophospholipids are not good substrates for plasmalogen formation, even when they are incorporated into microsomes.", "contents": "Studies of rat brain choline ethanolamine phosphotransferases using labeled alkylacylglycerol as substrate with evidence for reversibility of the reactions. Cholinephosphotransferase activity in brain microsomes may be assayed with labeled alkylacylglycerols or with CDP-choline with label in the phosphocholine with nearly identical results. The direct linear plot method was used for evaluation of Michaelis-Menten kinetic parameters. Most of the cholinephosphotransferase activity is in microsomes and a stimulatory factor seems to be present in the cytosol. Incubation of microsomes with labeled alkylacylglycerols and CDP-choline, in the initial absence of CDP-ethanolamine, produced labeled ethanolamine glycerophospholipids as well as labeled choline glycerophospholipids. Since the labeling of ethanolamine glycerophospholipids was increased by the addition of CMP, the labeling was probably due to the reversal of ethanolamine phosphotransferase to yield CDP-ethanolamine produced by the choline phosphotransferase reaction. Cholinephosphotransferase was reversed more readily than ethanolaminephosphotransferase in brain as it is in liver (Kanok and Ohno, 1973). Only trace quantities of plasmalogens were formed with labeled alkylacylglycerols. Previous results of plasmalogen labeling from labeled CDP-nucleotides were apparently due to reversal of phosphotransferase reactions. Alkylacylglycerophospholipids are not good substrates for plasmalogen formation, even when they are incorporated into microsomes."}
{"id": "PMID:208367", "title": "Adsorption and activation of pancreatic lipase at interfaces.", "content": "The first step of the lipase-catalyzed hydrolysis of insoluble long chain triglycerides is the adsorption of the enzyme to the interface. This adsorption, which is spontaneous when the interface is hydrophobic, is hindered by bile salts. Under these conditions, a small protein cofactor designated colipase adsorbs first and then anchors lipase at the interface. Interfacial adsorption enhances lipase activity, due, at least in part, to an acceleration of the rate-limiting deacylation step of the reaction. In this respect, lipase appears to be a most interesting model of an enzyme being activated by the presence of a lipid. The 3 steps of the heterogeneous catalysis induced by lipase, interfacial adsorption, interfacial activation and catalysis proper are under the control, respectively, of a serine hydroxyl group, a carboxyl and a histidine imidazole.", "contents": "Adsorption and activation of pancreatic lipase at interfaces. The first step of the lipase-catalyzed hydrolysis of insoluble long chain triglycerides is the adsorption of the enzyme to the interface. This adsorption, which is spontaneous when the interface is hydrophobic, is hindered by bile salts. Under these conditions, a small protein cofactor designated colipase adsorbs first and then anchors lipase at the interface. Interfacial adsorption enhances lipase activity, due, at least in part, to an acceleration of the rate-limiting deacylation step of the reaction. In this respect, lipase appears to be a most interesting model of an enzyme being activated by the presence of a lipid. The 3 steps of the heterogeneous catalysis induced by lipase, interfacial adsorption, interfacial activation and catalysis proper are under the control, respectively, of a serine hydroxyl group, a carboxyl and a histidine imidazole."}
{"id": "PMID:208384", "title": "Effect of adenosine and catecholamines on cyclic AMP levels in guinea pig heart.", "content": "Adenosine has been shown to stimulate cyclic AMP accumulation in guinea pig atrial and ventricular slice preparations in a rapid and dose-dependent manner. Response to adenosine was inhibited by therophylline, potentiated by several other phosphodiesterase inhibitors and unaffected by alpha- or beta-adrenergic blocking agents. Agonist action required free hydroxyl groups at 2', 3', and 5' positions on the ribosyl moiety, retention of one proton on the 6-amino group, N at position 7, and unsubstituted C at position 8 on the purine moiety. The combined action between adenosine and isoproterenol was the sum of the individual stimulations. The alpha-agonist action of epinephrine and norepinephrine reduced cyclic AMP levels stimulated by beta-agonist or by adenosine; this action was mimicked by methoxamine. The effect of an alpha-agonist was particularly pronounced when cyclic AMP levels were elevated by adenosine.", "contents": "Effect of adenosine and catecholamines on cyclic AMP levels in guinea pig heart. Adenosine has been shown to stimulate cyclic AMP accumulation in guinea pig atrial and ventricular slice preparations in a rapid and dose-dependent manner. Response to adenosine was inhibited by therophylline, potentiated by several other phosphodiesterase inhibitors and unaffected by alpha- or beta-adrenergic blocking agents. Agonist action required free hydroxyl groups at 2', 3', and 5' positions on the ribosyl moiety, retention of one proton on the 6-amino group, N at position 7, and unsubstituted C at position 8 on the purine moiety. The combined action between adenosine and isoproterenol was the sum of the individual stimulations. The alpha-agonist action of epinephrine and norepinephrine reduced cyclic AMP levels stimulated by beta-agonist or by adenosine; this action was mimicked by methoxamine. The effect of an alpha-agonist was particularly pronounced when cyclic AMP levels were elevated by adenosine."}
{"id": "PMID:208386", "title": "Cyclic AMP-dependent phosphorylation of the actin-binding protein filamin.", "content": "Filamin is a high molecular weight protein that binds to actin filaments in cells. It is found in large amounts in several different cells and tissues, including smooth muscle, fibroblasts, platelets, and macrophages. It is immunologically related to the previously described macrophage high molecular weight actin-binding protein but clearly different from erythrocyte spectrin. Filamin is a phosphoprotein; it is phosphorylated in vivo in intact tissues and cells. It can be phosphorylated in vitro with endogenous kinases; cyclic AMP stimulates this phosohorylation. Furthermore, the purified protein can be phosphorylated by purified cyclic AMP-dependent protein kinase. In smooth muscle homogenates, the stimulation of filamin phosphorylation by cyclic AMP is specific. Cyclic GMP and Ca2+ do not increase its phosphorylation, although they do stimulate phosphorylation of other proteins.", "contents": "Cyclic AMP-dependent phosphorylation of the actin-binding protein filamin. Filamin is a high molecular weight protein that binds to actin filaments in cells. It is found in large amounts in several different cells and tissues, including smooth muscle, fibroblasts, platelets, and macrophages. It is immunologically related to the previously described macrophage high molecular weight actin-binding protein but clearly different from erythrocyte spectrin. Filamin is a phosphoprotein; it is phosphorylated in vivo in intact tissues and cells. It can be phosphorylated in vitro with endogenous kinases; cyclic AMP stimulates this phosohorylation. Furthermore, the purified protein can be phosphorylated by purified cyclic AMP-dependent protein kinase. In smooth muscle homogenates, the stimulation of filamin phosphorylation by cyclic AMP is specific. Cyclic GMP and Ca2+ do not increase its phosphorylation, although they do stimulate phosphorylation of other proteins."}
{"id": "PMID:208389", "title": "Mechanisms of catecholamine actions on liver carbohydrate metabolism.", "content": "Epinephrine rapidly activates phosphorylase in hepatocytes, mainly by a mechanism(s) involving alpha-adrenergic and not beta-adrenergic receptors. The alpha-adrenergic mechanism does not involve accumulation of cAMP or activation of cAMP-dependent protein kinase. It is impaired when hepatocytes are depleted of calcium by EGTA treatment and is rapidly restored by readdition of calcium. Basal phosphorylase is also lowered by calcium deficiency and rapidly increased by calcium but not other divalent cations. The divalent cation ioniphore A23187 increases phosphorylase a levels in hepatocytes in a calcium-dependent manner. Calcium deficiency does not modify the effects of glucagon, cAMP, or beta-adrenergic activation on phosphorylase. Activation of alpha-adrenergic receptors rapidly increases 45Ca fluxes in hepatocytes. Glucagon produces similar effects, but supraphysiological concentrations are required. The hypothesis is advanced that alpha-adrenergic activation of phosphorylase involves alterations in cell calcium such that there is an increase in cytosolic Ca2+ concentration leading to increased phosphorylase kinase activity. Epinephrine induces greater cAMP accumulation in calcium-depleted cells than in normal cells. The effect is mediated by alpha-adrenergic and not beta-adrenergic receptors. Calcium deficiency also cuases cAMP accumulation in hepatocytes incubated with phenylephrine but does not modify the responses of the cells to isoproterenol, glucagon, or cAMP. Low concentrations of calcium rapidly reverse alpha-adrenergic receptor-mediated cAMP accumulation in calcium-depleted cells. The hypothesis is advanced that calcium normally exerts an inhibitory effect on a linkage between alpha-adrenergic receptors and adenylate cyclase in hepatocytes.", "contents": "Mechanisms of catecholamine actions on liver carbohydrate metabolism. Epinephrine rapidly activates phosphorylase in hepatocytes, mainly by a mechanism(s) involving alpha-adrenergic and not beta-adrenergic receptors. The alpha-adrenergic mechanism does not involve accumulation of cAMP or activation of cAMP-dependent protein kinase. It is impaired when hepatocytes are depleted of calcium by EGTA treatment and is rapidly restored by readdition of calcium. Basal phosphorylase is also lowered by calcium deficiency and rapidly increased by calcium but not other divalent cations. The divalent cation ioniphore A23187 increases phosphorylase a levels in hepatocytes in a calcium-dependent manner. Calcium deficiency does not modify the effects of glucagon, cAMP, or beta-adrenergic activation on phosphorylase. Activation of alpha-adrenergic receptors rapidly increases 45Ca fluxes in hepatocytes. Glucagon produces similar effects, but supraphysiological concentrations are required. The hypothesis is advanced that alpha-adrenergic activation of phosphorylase involves alterations in cell calcium such that there is an increase in cytosolic Ca2+ concentration leading to increased phosphorylase kinase activity. Epinephrine induces greater cAMP accumulation in calcium-depleted cells than in normal cells. The effect is mediated by alpha-adrenergic and not beta-adrenergic receptors. Calcium deficiency also cuases cAMP accumulation in hepatocytes incubated with phenylephrine but does not modify the responses of the cells to isoproterenol, glucagon, or cAMP. Low concentrations of calcium rapidly reverse alpha-adrenergic receptor-mediated cAMP accumulation in calcium-depleted cells. The hypothesis is advanced that calcium normally exerts an inhibitory effect on a linkage between alpha-adrenergic receptors and adenylate cyclase in hepatocytes."}
{"id": "PMID:208405", "title": "Regulation of aldosterone secretion: current concepts and newer aspects.", "content": "Four humoral factors have been shown to play important roles in the regulation of aldosterone secretion. These are ACTH, potassium, sodium and angiotensin II. ACTH appears to play little or no role in the maintenance of adrenal zona glomerulosa cells in response to specific stimuli. However, there is evidence to show that physiologic levels of ACTH regulate the  minute-to-minute fluctuations of plasma aldosterone. In man and in experimental animals, alterations in potassium balance as well as acute increments in serum potassium can stimulate aldosterone production. The importance of potassium ion in the control of aldosterone secretion can be fully appreciated by the demonstration that aldosterone responses to other stimuli are subnormal in the presence of potassium depletion. Changes in dietary sodium can alter the aldosterone response to a number of acute stimuli. Sodium deprivation enhances aldosterone responses to ACTH infusion, potassium loading and angiotensin II administration. Enhanced conversion of corticosterone to aldosterone (due to sodium depletion) coupled with an acute stimulus acting at an earlier step in aldosterone biosynthesis probably explains the sensitizing effect of dietary sodium restriction. In recent years, indirect evidence has emerged to suggest that the COOH-terminal heptapeptide fragment of angiotensin II may mediate the aldosterone-stimulating activity of the renin-angiotensin system. The evidence has been derived from in vivo and in vitro studies indicating that angiotensin II and the heptapeptide stimulate aldosterone production equally well and that their relative binding potencies to adrenal zona glomerulosa cells are identical. In addition, heptapeptide antagonists are potent and specific inhibitors of angiotensin II-induced aldosterone biosynthesis. However, the data do not preclude the possibility that angiotensin II could stimulate aldosterone production without prior conversion to the heptapeptide.", "contents": "Regulation of aldosterone secretion: current concepts and newer aspects. Four humoral factors have been shown to play important roles in the regulation of aldosterone secretion. These are ACTH, potassium, sodium and angiotensin II. ACTH appears to play little or no role in the maintenance of adrenal zona glomerulosa cells in response to specific stimuli. However, there is evidence to show that physiologic levels of ACTH regulate the  minute-to-minute fluctuations of plasma aldosterone. In man and in experimental animals, alterations in potassium balance as well as acute increments in serum potassium can stimulate aldosterone production. The importance of potassium ion in the control of aldosterone secretion can be fully appreciated by the demonstration that aldosterone responses to other stimuli are subnormal in the presence of potassium depletion. Changes in dietary sodium can alter the aldosterone response to a number of acute stimuli. Sodium deprivation enhances aldosterone responses to ACTH infusion, potassium loading and angiotensin II administration. Enhanced conversion of corticosterone to aldosterone (due to sodium depletion) coupled with an acute stimulus acting at an earlier step in aldosterone biosynthesis probably explains the sensitizing effect of dietary sodium restriction. In recent years, indirect evidence has emerged to suggest that the COOH-terminal heptapeptide fragment of angiotensin II may mediate the aldosterone-stimulating activity of the renin-angiotensin system. The evidence has been derived from in vivo and in vitro studies indicating that angiotensin II and the heptapeptide stimulate aldosterone production equally well and that their relative binding potencies to adrenal zona glomerulosa cells are identical. In addition, heptapeptide antagonists are potent and specific inhibitors of angiotensin II-induced aldosterone biosynthesis. However, the data do not preclude the possibility that angiotensin II could stimulate aldosterone production without prior conversion to the heptapeptide."}
{"id": "PMID:208409", "title": "Serological studies in the elderly.", "content": "Sera from 108 elderly patients in psychiatric and general hospitals were tested for antibodies to seven viruses. Measles virus antibody levels were significantly higher in patients from the psychiatric hospital, regardless of diagnosis, than in those from other hospitals. Demented patients, regardless of their hospital, had significantly higher levels of antibody to adenovirus than control patients.", "contents": "Serological studies in the elderly. Sera from 108 elderly patients in psychiatric and general hospitals were tested for antibodies to seven viruses. Measles virus antibody levels were significantly higher in patients from the psychiatric hospital, regardless of diagnosis, than in those from other hospitals. Demented patients, regardless of their hospital, had significantly higher levels of antibody to adenovirus than control patients."}
{"id": "PMID:208416", "title": "Receptor dysfunction and hormone resistance in human diseases--a review.", "content": "Studies of the hormone-receptor interaction have introduced a new chapter in endocrine and metabolic disorders. Receptor (R) dysfunction in human diseases, due either to an alteration in the number or affinity of the R, or to antibodies against the R, is reviewed and classified in the first part of this paper. Disorders where hormone resistance has been implicated, but where R studies are still unavailable are also presented.", "contents": "Receptor dysfunction and hormone resistance in human diseases--a review. Studies of the hormone-receptor interaction have introduced a new chapter in endocrine and metabolic disorders. Receptor (R) dysfunction in human diseases, due either to an alteration in the number or affinity of the R, or to antibodies against the R, is reviewed and classified in the first part of this paper. Disorders where hormone resistance has been implicated, but where R studies are still unavailable are also presented."}
{"id": "PMID:208417", "title": "A comparison of the adrenal responses to hypoglycemia, metyrapone and ACTH.", "content": "The adrenal responses to insulin-induced hypoglycemia and the rapid adrenocorticotropic hormone (ACTH) stimulation test were compared in 24 healthy volunteers, 18 of whom also underwent a rapid oral metyrapone test. The cortisol levels after hypoglycemia (18.0-30.0 microgram/100 ml) were similar to and directly related to the levels after ACTH (21.0-31.0 microgram/100 ml). The levels after both stimuli were independent of age, sex, height, and weight. The 11-deoxycortisol response to the metyrapone test was less than the cortisol response to hypoglycemia and metyrapone administration was associated with more unpleasant side effects. In a group of 69 control subjects, the post-ACTH cortisol levels were 15.0 to 80.0 microgram/100 ml while in seven patients with Addison's disease they were less than 1-4.5 microgram/100 ml. In 44 control subjects, the posthypoglycemia cortisol levels were 18.0 to 30.0 microgram/100 ml compared with less than 1.0-9.0 microgram/100 ml in 22 patients with hypopituitarism. The absolute poststimulation cortisol levels provided better separation of control subjects from patients with adrenal or pituitary insufficiency than either the increment in cortisol levels or the 11-deoxycortisol response to metyrapone.", "contents": "A comparison of the adrenal responses to hypoglycemia, metyrapone and ACTH. The adrenal responses to insulin-induced hypoglycemia and the rapid adrenocorticotropic hormone (ACTH) stimulation test were compared in 24 healthy volunteers, 18 of whom also underwent a rapid oral metyrapone test. The cortisol levels after hypoglycemia (18.0-30.0 microgram/100 ml) were similar to and directly related to the levels after ACTH (21.0-31.0 microgram/100 ml). The levels after both stimuli were independent of age, sex, height, and weight. The 11-deoxycortisol response to the metyrapone test was less than the cortisol response to hypoglycemia and metyrapone administration was associated with more unpleasant side effects. In a group of 69 control subjects, the post-ACTH cortisol levels were 15.0 to 80.0 microgram/100 ml while in seven patients with Addison's disease they were less than 1-4.5 microgram/100 ml. In 44 control subjects, the posthypoglycemia cortisol levels were 18.0 to 30.0 microgram/100 ml compared with less than 1.0-9.0 microgram/100 ml in 22 patients with hypopituitarism. The absolute poststimulation cortisol levels provided better separation of control subjects from patients with adrenal or pituitary insufficiency than either the increment in cortisol levels or the 11-deoxycortisol response to metyrapone."}
{"id": "PMID:208421", "title": "Intermittent occlusion of the hepatic artery and infusion chemotherapy for carcinoma of the liver.", "content": "Twenty-nine patients with hepatocellular or metastatic colon carcinoma were included in the present study. A system of staging the extent of disease was developed to provide a guideline for patient selection and evaluation of the results of therapy. Sixteen patients received intraarterial infusion chemotherapy only and thirteen were treated by a combination of intermittent occlusion of the hepatic artery and infusion chemotherapy. In this latter group intermittent occlusion of the hepatic artery was employed as an alternative to hepatic artery ligation. Patients in either group having disease confined to the liver experienced good response to treatment, had a low incidence of drug-related complications, and survived for relatively long periods. The study confirmed that intermittent occlusion of the hepatic artery is a safe procedure and that it is not accompanied by an increase in morbidity or mortality. The rationale for using this technic and the advantages it has over hepatic artery ligation were presented. The procedure is currently being utilized with increasing frequency in patients in relatively early stages of the disease. Accumulation of more material and longer periods of follow-up are required to determine the therapeutic advantages of the new method over infusion chemotherapy alone.", "contents": "Intermittent occlusion of the hepatic artery and infusion chemotherapy for carcinoma of the liver. Twenty-nine patients with hepatocellular or metastatic colon carcinoma were included in the present study. A system of staging the extent of disease was developed to provide a guideline for patient selection and evaluation of the results of therapy. Sixteen patients received intraarterial infusion chemotherapy only and thirteen were treated by a combination of intermittent occlusion of the hepatic artery and infusion chemotherapy. In this latter group intermittent occlusion of the hepatic artery was employed as an alternative to hepatic artery ligation. Patients in either group having disease confined to the liver experienced good response to treatment, had a low incidence of drug-related complications, and survived for relatively long periods. The study confirmed that intermittent occlusion of the hepatic artery is a safe procedure and that it is not accompanied by an increase in morbidity or mortality. The rationale for using this technic and the advantages it has over hepatic artery ligation were presented. The procedure is currently being utilized with increasing frequency in patients in relatively early stages of the disease. Accumulation of more material and longer periods of follow-up are required to determine the therapeutic advantages of the new method over infusion chemotherapy alone."}
{"id": "PMID:208426", "title": "Antibiotic-induced paralysis of the mouse phrenic nerve-hemidiaphragm preparation, and reversibility by calcium and by neostigmine.", "content": "Certain antibiotics can induce neuromuscular paralysis, but the mechanism of this action is largely unknown. The purpose of this study was to compare the neuromuscular blocking potencies and reversibilities of 16 antibiotics in the isolated mouse phrenic nerve-hemidiaphragm preparation. The antibiotics tested were five aminoglycosides (neomycin, gentamicin, streptomycin, dihydrostreptomycin and kanamycin), tetracycline and oxytetracycline, polymyxins B and E, penicillins G and V, cephradine, cephaloridine, erythromycin, lincomycin, and clindamycin. Reversibility of the muscle paralysis by calcium and neostigmine was assessed. All the aminoglycosides resembled magnesium in blocking neuromuscular transmission, the neuromuscular blockade being almost completely reversed (to 64-77 per cent of control) by calcium but only poorly reversed by neostigmine (to 20-67 per cent of control). Neuromuscular blockade produced by the tetracyclines was also reversed by calcium (44-104 per cent) but not by neostigmine (0-15 per cent). Neuromuscular blockade produced by the polymyxins or by lincomycin was only partially reversed by calcium (0-34 per cent). Penicillin V, erythromycin, clindamycin, polymyxin B and the tetracyclines could also produce muscle paralysis by decreasing muscle contractility. This effect on contractility was irreversible by pharmacologic means. Penicillin G, cephradine and cephaloridine possessed negligible paralyzing effects on the nerve-muscle preparation. It is concluded that the different groups of antibiotics tested act by different mechanisms and that only the calcium-induced reversal of aminoglycoside block is predictable.", "contents": "Antibiotic-induced paralysis of the mouse phrenic nerve-hemidiaphragm preparation, and reversibility by calcium and by neostigmine. Certain antibiotics can induce neuromuscular paralysis, but the mechanism of this action is largely unknown. The purpose of this study was to compare the neuromuscular blocking potencies and reversibilities of 16 antibiotics in the isolated mouse phrenic nerve-hemidiaphragm preparation. The antibiotics tested were five aminoglycosides (neomycin, gentamicin, streptomycin, dihydrostreptomycin and kanamycin), tetracycline and oxytetracycline, polymyxins B and E, penicillins G and V, cephradine, cephaloridine, erythromycin, lincomycin, and clindamycin. Reversibility of the muscle paralysis by calcium and neostigmine was assessed. All the aminoglycosides resembled magnesium in blocking neuromuscular transmission, the neuromuscular blockade being almost completely reversed (to 64-77 per cent of control) by calcium but only poorly reversed by neostigmine (to 20-67 per cent of control). Neuromuscular blockade produced by the tetracyclines was also reversed by calcium (44-104 per cent) but not by neostigmine (0-15 per cent). Neuromuscular blockade produced by the polymyxins or by lincomycin was only partially reversed by calcium (0-34 per cent). Penicillin V, erythromycin, clindamycin, polymyxin B and the tetracyclines could also produce muscle paralysis by decreasing muscle contractility. This effect on contractility was irreversible by pharmacologic means. Penicillin G, cephradine and cephaloridine possessed negligible paralyzing effects on the nerve-muscle preparation. It is concluded that the different groups of antibiotics tested act by different mechanisms and that only the calcium-induced reversal of aminoglycoside block is predictable."}
{"id": "PMID:208428", "title": "Chromatographic analysis of multiple tracer inert gases in the presence of anesthetic gases.", "content": "A gas chromatographic method for simultaneous analysis of multiple tracer inert gases in blood and expired gas samples is described. The method enables determination of the distribution of ventilation-perfusion ratios in the lungs during anesthesia with nitrous oxide and halothane. In addition, simultaneous analysis of anesthetic gas concentration in blood permits calculation of the amount of uptake or elimination of anesthetic gases from the Fick principle.", "contents": "Chromatographic analysis of multiple tracer inert gases in the presence of anesthetic gases. A gas chromatographic method for simultaneous analysis of multiple tracer inert gases in blood and expired gas samples is described. The method enables determination of the distribution of ventilation-perfusion ratios in the lungs during anesthesia with nitrous oxide and halothane. In addition, simultaneous analysis of anesthetic gas concentration in blood permits calculation of the amount of uptake or elimination of anesthetic gases from the Fick principle."}
{"id": "PMID:208429", "title": "A comparison of a theophylline-ephedrine combination with terbutaline.", "content": "In a single-blind, crossover study 10 adult asthmatic patients received a theophylline-ephedrine combination tablet (theophylline 90 mg, ephedrine 16 mg and phenobarbital 25 mg in an immediate release layer and theophylline 90 mg and ephedrine 32 mg in a sustained release layer) twice daily or terbutaline 5 mg three times daily for two weeks. There was no significant difference in bronchodilator response to a single dose of the study drugs on either the initial day of treatment or after two weeks of continuous therapy. Mean increases in serum cyclic-AMP levels produced by both drugs were not significantly different. Mean peak plasma theophylline levels were 2.9 +/- 1.3 microgram/ml following the initial dose and 7.3 +/- 3.4 microgram/ml after two weeks of continuous dosing with the combination drug. No adverse effects on blood pressure or pulse rate were observed to either drug. Overall, the incidence and severity of reported side effects (tremor, nausea and nervousness) were less with the theophylline-ephedrine combination.", "contents": "A comparison of a theophylline-ephedrine combination with terbutaline. In a single-blind, crossover study 10 adult asthmatic patients received a theophylline-ephedrine combination tablet (theophylline 90 mg, ephedrine 16 mg and phenobarbital 25 mg in an immediate release layer and theophylline 90 mg and ephedrine 32 mg in a sustained release layer) twice daily or terbutaline 5 mg three times daily for two weeks. There was no significant difference in bronchodilator response to a single dose of the study drugs on either the initial day of treatment or after two weeks of continuous therapy. Mean increases in serum cyclic-AMP levels produced by both drugs were not significantly different. Mean peak plasma theophylline levels were 2.9 +/- 1.3 microgram/ml following the initial dose and 7.3 +/- 3.4 microgram/ml after two weeks of continuous dosing with the combination drug. No adverse effects on blood pressure or pulse rate were observed to either drug. Overall, the incidence and severity of reported side effects (tremor, nausea and nervousness) were less with the theophylline-ephedrine combination."}
{"id": "PMID:208431", "title": "Protides of the Mustelidae: immunoresponse of mustelids to Aleutian mink disease virus.", "content": "Members of North American Mustelidae were tested for their response to inoculation with 10(6) infective doses of Aleutian disease virus. In subfamily Mustelinae, 3 species in the genus Mustela (M vision, M erminea, and M putorius) and 2 species in genus Martes (Ma pennanti and Ma americana) responded immunologically with some features resembling Aleutian disease in mink. In subfamily Mephitinae, only Mephitis mephitis responded, and others of the subfamily did not, nor did members of subfamilies Melinae and Lutrinae. The responses observed ranged from development of detectable antibody levels determined by counterimmunoelectrophoresis to histopathologic changes typical of Aleutian disease.", "contents": "Protides of the Mustelidae: immunoresponse of mustelids to Aleutian mink disease virus. Members of North American Mustelidae were tested for their response to inoculation with 10(6) infective doses of Aleutian disease virus. In subfamily Mustelinae, 3 species in the genus Mustela (M vision, M erminea, and M putorius) and 2 species in genus Martes (Ma pennanti and Ma americana) responded immunologically with some features resembling Aleutian disease in mink. In subfamily Mephitinae, only Mephitis mephitis responded, and others of the subfamily did not, nor did members of subfamilies Melinae and Lutrinae. The responses observed ranged from development of detectable antibody levels determined by counterimmunoelectrophoresis to histopathologic changes typical of Aleutian disease."}
{"id": "PMID:208432", "title": "Maintenance of foals with combined immunodeficiency: causes and control of secondary infections.", "content": "Sixty-six cases of combined immunodeficiency (CID) in foals were studied to determine the most prevalent causes of infection and death. Lesions of the respiratory system were observed in 59 of the foals and were attributable to infection with equine adenovirus. Pneumocystis carinii, and bacteria. Significant lesions were also observed in liver, pancreas, intestines, heart, and kidneys. Maintenance of foals with CID for experimental purposes is directed at the prevention and control of these secondary infections. Adenovirus can be controlled by administration of horse plasma containing high titers of antiadenovirus antibody. Bacteria are controlled by appropriate antibiotic therapy. Pneumocystis carinii infection remains a significant problem in the maintenance of foals with CID.", "contents": "Maintenance of foals with combined immunodeficiency: causes and control of secondary infections. Sixty-six cases of combined immunodeficiency (CID) in foals were studied to determine the most prevalent causes of infection and death. Lesions of the respiratory system were observed in 59 of the foals and were attributable to infection with equine adenovirus. Pneumocystis carinii, and bacteria. Significant lesions were also observed in liver, pancreas, intestines, heart, and kidneys. Maintenance of foals with CID for experimental purposes is directed at the prevention and control of these secondary infections. Adenovirus can be controlled by administration of horse plasma containing high titers of antiadenovirus antibody. Bacteria are controlled by appropriate antibiotic therapy. Pneumocystis carinii infection remains a significant problem in the maintenance of foals with CID."}
{"id": "PMID:208433", "title": "Equine grass sickness: serologic evidence of association with Clostridium perfringens type A enterotoxin.", "content": "Clostridium perfringens type A enterotoxin seroneutralization was carried out on sera from 50 horses recovered from grass sickness and from 100 other horses with no record of having had the disease. Of the affected horses, 70% had seroneutralizating titers higher than 1:64, half of these being equal or higher than 1:128. More than 88% of the horses with no record of grass sickness had titers lower than 1:64. These data support the theory of association between C perfringens type A toxins and grass sickness.", "contents": "Equine grass sickness: serologic evidence of association with Clostridium perfringens type A enterotoxin. Clostridium perfringens type A enterotoxin seroneutralization was carried out on sera from 50 horses recovered from grass sickness and from 100 other horses with no record of having had the disease. Of the affected horses, 70% had seroneutralizating titers higher than 1:64, half of these being equal or higher than 1:128. More than 88% of the horses with no record of grass sickness had titers lower than 1:64. These data support the theory of association between C perfringens type A toxins and grass sickness."}
{"id": "PMID:208434", "title": "Intrafetal inoculation of swine with transmissible gastroenteritis virus.", "content": "Fetuses in 3 sows were inoculated (intramuscularly) with transmissible gastroenteritis (TGE) virus on 95th, 77th, and 74th days of the gestation. At 15, 14, and 37 days later (or days when pigs were obtained by hysterectomy), there was evidence of intestinal localization of virus, with villous atrophy and subsequent repair. All intrafetal-inoculated pigs became serologic-positive for TGE. A noninoculated pig shown to be seropositive for TGE at 15 days of age (after hysterectomy) was resistant to challenge exposure with virulent TGE virus given on the 32nd day, in contrast to 3 seronegative littermates that developed typical disease when challenge exposed.", "contents": "Intrafetal inoculation of swine with transmissible gastroenteritis virus. Fetuses in 3 sows were inoculated (intramuscularly) with transmissible gastroenteritis (TGE) virus on 95th, 77th, and 74th days of the gestation. At 15, 14, and 37 days later (or days when pigs were obtained by hysterectomy), there was evidence of intestinal localization of virus, with villous atrophy and subsequent repair. All intrafetal-inoculated pigs became serologic-positive for TGE. A noninoculated pig shown to be seropositive for TGE at 15 days of age (after hysterectomy) was resistant to challenge exposure with virulent TGE virus given on the 32nd day, in contrast to 3 seronegative littermates that developed typical disease when challenge exposed."}
{"id": "PMID:208435", "title": "Distribution of Bovid herpesvirus 2 in calves inoculated intravenously.", "content": "The behavior of Bovid herpesvirus 2 in the skin, lymph nodes, and nervous system of calves injected intravenously with the virus was studied. After a latent phase that lasted up to 40 hours after inoculation, the virus produced a systemic infection which was characterized by primary localization of virus in the skin, lymph nodes, and nervous system. Between postinoculation days 7 and 12, the infection tended to persist in the skin only. The finding of intranuclear inclusions in the pyramidal cells of the cerebral cortex and in the neurons of the superior cervical and stellate ganglia supports the hypothesis that the virus might utilize the structures of the nervous system for its replicative cycle in the calf.", "contents": "Distribution of Bovid herpesvirus 2 in calves inoculated intravenously. The behavior of Bovid herpesvirus 2 in the skin, lymph nodes, and nervous system of calves injected intravenously with the virus was studied. After a latent phase that lasted up to 40 hours after inoculation, the virus produced a systemic infection which was characterized by primary localization of virus in the skin, lymph nodes, and nervous system. Between postinoculation days 7 and 12, the infection tended to persist in the skin only. The finding of intranuclear inclusions in the pyramidal cells of the cerebral cortex and in the neurons of the superior cervical and stellate ganglia supports the hypothesis that the virus might utilize the structures of the nervous system for its replicative cycle in the calf."}
{"id": "PMID:208436", "title": "Influence of thymectomy on the susceptibility of cats to feline leukemia virus and lymphosarcoma.", "content": "Twelve cats were thymectomized at 5 weeks of age. Six of these cats were inoculated at 8 weeks of age and 6 at 4 months of age with the Rickard (R) strain of feline leukemia virus (FeLV), which produces a high incidence of thymic lymphosarcoma. Two groups of age-matched nonthymectomized cats were inoculated with the same FeLV-R stock. Thymectomy prior to FeLV infection had no influence on the induction of viremia or the incidence of lymphosarcoma. In the FeLV-inoculated nonthymectomized cats, lymphosarcoma developed in the thymus. In the thymectomized cats, lymphosarcoma developed in the intestine, mesenteric lymph nodes, and bone marrow, but the malignant lymphoblasts had surface markers characteristic of feline T lymphocytes. It was concluded that the presence of the thymus per se is not required for infection and oncogenesis by FeLV and that feline T lymphocytes may be transformed after peripheralization to other tissues.", "contents": "Influence of thymectomy on the susceptibility of cats to feline leukemia virus and lymphosarcoma. Twelve cats were thymectomized at 5 weeks of age. Six of these cats were inoculated at 8 weeks of age and 6 at 4 months of age with the Rickard (R) strain of feline leukemia virus (FeLV), which produces a high incidence of thymic lymphosarcoma. Two groups of age-matched nonthymectomized cats were inoculated with the same FeLV-R stock. Thymectomy prior to FeLV infection had no influence on the induction of viremia or the incidence of lymphosarcoma. In the FeLV-inoculated nonthymectomized cats, lymphosarcoma developed in the thymus. In the thymectomized cats, lymphosarcoma developed in the intestine, mesenteric lymph nodes, and bone marrow, but the malignant lymphoblasts had surface markers characteristic of feline T lymphocytes. It was concluded that the presence of the thymus per se is not required for infection and oncogenesis by FeLV and that feline T lymphocytes may be transformed after peripheralization to other tissues."}
{"id": "PMID:208438", "title": "[Polysyndactily with double pyeloureteral system (author's transl)].", "content": "A case of dominant polysyndactily with double pyeloureteral system is described and the relationships between anomalies of the limb and of the urologic system are discussed, with particular emphasis in the acro-renal syndrome.", "contents": "[Polysyndactily with double pyeloureteral system (author's transl)]. A case of dominant polysyndactily with double pyeloureteral system is described and the relationships between anomalies of the limb and of the urologic system are discussed, with particular emphasis in the acro-renal syndrome."}
{"id": "PMID:208439", "title": "1,25 dihydroxycholecalciferol effects in chronic dialysis. A double-blind controlled study.", "content": "1,25 dihydroxycholecalciferol [1,25(OH)2D3] was studied in a double-blind controlled fashion in patients on chronic dialysis. Serum calcium was unchanged in 16 patients on vitamin D3 (D3) (400 to 1200 IU/day). In 15 patients on 1,25(OH)2D3 (0.5 to 1.5 microgram/day), serum calcium increased from 9.05 +/- .15 to 10.25 +/- .20 mg/dl (p less than 0.001), returning to 9.37 +/- .16 mg/dl (p less than 0.001) in the post control period. Patients on D3 showed no reversible decrease in immunoreactive parathyroid hormone levels, but patients on 1,25(OH)2D3 did, from a control of 1077 +/- 258 to 595 +/- 213 microliter equivalents/ml (p less than 0.01), and returned to 1165 +/- 271 microliter equivalents/ml (p less than 0.005). Nine of 12 patients on D3 who underwent serial iliac-crest biopsies showed histologic deterioration, and six of seven who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium decreased in patients on D3 (p less than 0.05) but not in those on 1,25(OH)2D3. Hypercalcemia occurred in five of 15 patients. We conclude that 1,25(OH)2D3 has a calcemic effect in chronic dialysis patients, decreases levels of immunoreactive parathyroid hormone, and is associated with histologic improvement in bone disease. Thus, 1,25(OH)2D3 is a valuable adjunct to the management of renal osteodystrophy but requires monitoring of serum calcium to avoid hypercalcemia.", "contents": "1,25 dihydroxycholecalciferol effects in chronic dialysis. A double-blind controlled study. 1,25 dihydroxycholecalciferol [1,25(OH)2D3] was studied in a double-blind controlled fashion in patients on chronic dialysis. Serum calcium was unchanged in 16 patients on vitamin D3 (D3) (400 to 1200 IU/day). In 15 patients on 1,25(OH)2D3 (0.5 to 1.5 microgram/day), serum calcium increased from 9.05 +/- .15 to 10.25 +/- .20 mg/dl (p less than 0.001), returning to 9.37 +/- .16 mg/dl (p less than 0.001) in the post control period. Patients on D3 showed no reversible decrease in immunoreactive parathyroid hormone levels, but patients on 1,25(OH)2D3 did, from a control of 1077 +/- 258 to 595 +/- 213 microliter equivalents/ml (p less than 0.01), and returned to 1165 +/- 271 microliter equivalents/ml (p less than 0.005). Nine of 12 patients on D3 who underwent serial iliac-crest biopsies showed histologic deterioration, and six of seven who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium decreased in patients on D3 (p less than 0.05) but not in those on 1,25(OH)2D3. Hypercalcemia occurred in five of 15 patients. We conclude that 1,25(OH)2D3 has a calcemic effect in chronic dialysis patients, decreases levels of immunoreactive parathyroid hormone, and is associated with histologic improvement in bone disease. Thus, 1,25(OH)2D3 is a valuable adjunct to the management of renal osteodystrophy but requires monitoring of serum calcium to avoid hypercalcemia."}
{"id": "PMID:208442", "title": "Mumps vaccine. Recommendation of the Public Health Service Advisory Committee on Immunization Practices. Center for Disease Control, U.S. Department of Health, Education, and Welfare; Atlanta, Georgia.", "content": "This statement from the Center for Disease Control very briefly summarizes the characteristics of mumps, and then describes live-mumps-virus vaccine, including adverse effects and immunity response. The use of the vaccine is reviewed, for dosage, in relation to age, and precautions and contraindications. Five bibliographic references are appended.", "contents": "Mumps vaccine. Recommendation of the Public Health Service Advisory Committee on Immunization Practices. Center for Disease Control, U.S. Department of Health, Education, and Welfare; Atlanta, Georgia. This statement from the Center for Disease Control very briefly summarizes the characteristics of mumps, and then describes live-mumps-virus vaccine, including adverse effects and immunity response. The use of the vaccine is reviewed, for dosage, in relation to age, and precautions and contraindications. Five bibliographic references are appended."}
{"id": "PMID:208444", "title": "The biology and pathology of oxygen radicals.", "content": "Superoxide radicals (O2-) are commonplace products of the biological reduction of oxygen. Their intrinsic reactivity and ability to generate other more reactive entities constitute a threat to cellular integrity. Superoxide dismutases, enzymes that catalytically scavenge these radicals, have evolved to meet this threat. These metalloenzymes are essential for respiring organisms to survive. Several compounds, such as the antibiotic streptonigrin and the herbicide paraquat, augment the production rate of O2- inside cells. This accounts for the oxygen-enhancement of their lethality. Some bacteria respond to this artificially increased rate of O2- production by synthesizing additional superoxide dismutase. Ionizing radiation generates O2- in its passage through oxygenated aqueous media, and superoxide dismutase added to the suspending medium, decreases the oxygen-enhancement of the lethality of such irradiation of the bacterium Escherichia coli. Production of O2- by activated neutrophils is clinically significant, since it is an important component of the bactericidal actions of these cells and the inflammatory process. Superoxide dismutases exert an anti-inflammatory action that may be useful in managing inflammations.", "contents": "The biology and pathology of oxygen radicals. Superoxide radicals (O2-) are commonplace products of the biological reduction of oxygen. Their intrinsic reactivity and ability to generate other more reactive entities constitute a threat to cellular integrity. Superoxide dismutases, enzymes that catalytically scavenge these radicals, have evolved to meet this threat. These metalloenzymes are essential for respiring organisms to survive. Several compounds, such as the antibiotic streptonigrin and the herbicide paraquat, augment the production rate of O2- inside cells. This accounts for the oxygen-enhancement of their lethality. Some bacteria respond to this artificially increased rate of O2- production by synthesizing additional superoxide dismutase. Ionizing radiation generates O2- in its passage through oxygenated aqueous media, and superoxide dismutase added to the suspending medium, decreases the oxygen-enhancement of the lethality of such irradiation of the bacterium Escherichia coli. Production of O2- by activated neutrophils is clinically significant, since it is an important component of the bactericidal actions of these cells and the inflammatory process. Superoxide dismutases exert an anti-inflammatory action that may be useful in managing inflammations."}
{"id": "PMID:208448", "title": "Comparison of HSV1 DNA-induced and spontaneous transformation of hamster cells.", "content": "Primary cultures of hamster embryo fibroblasts were transfected by purified, fragmented herpes simplex virus type 1 (HSV1) strain A44 DNA in the presence of carrier DNA. Control cultures were transfected with carrier DNA only. A cell line transformed by HSV1 DNA (EH/A44 cell line) was established after serial passages, without senescent crisis. A control cell line (EHT cell line), spontaneously transformed in vitro, was established after a 13th passage crisis. Both cell lines originated from the same primary culture thereby allowing the comparison of virus DNA induced and spontaneous transformation. Various parameters were studies for both cell lines and their clones: cell growth in vitro, presence of viral antigens, permissivity to superinfection and oncogenicity.", "contents": "Comparison of HSV1 DNA-induced and spontaneous transformation of hamster cells. Primary cultures of hamster embryo fibroblasts were transfected by purified, fragmented herpes simplex virus type 1 (HSV1) strain A44 DNA in the presence of carrier DNA. Control cultures were transfected with carrier DNA only. A cell line transformed by HSV1 DNA (EH/A44 cell line) was established after serial passages, without senescent crisis. A control cell line (EHT cell line), spontaneously transformed in vitro, was established after a 13th passage crisis. Both cell lines originated from the same primary culture thereby allowing the comparison of virus DNA induced and spontaneous transformation. Various parameters were studies for both cell lines and their clones: cell growth in vitro, presence of viral antigens, permissivity to superinfection and oncogenicity."}
{"id": "PMID:208449", "title": "[Preliminary data on the protective effect of interferon coupled with liposomes in the mouse-virus model of murine hepatitis].", "content": "In MHV3-infected Balb/c mice the antiviral effect of murine interferon could be significantly enhanced by way of entrapment in cationic liposomes; these multi-lamellar spherules, made of egg lecithin, stearylamine and cholesterol, are supposed to exert a target effect leading to a greater accumulation of interferon in the liver and spleen. The possible use of liposomes as vectors of interferon in different viral pathologies is discussed.", "contents": "[Preliminary data on the protective effect of interferon coupled with liposomes in the mouse-virus model of murine hepatitis]. In MHV3-infected Balb/c mice the antiviral effect of murine interferon could be significantly enhanced by way of entrapment in cationic liposomes; these multi-lamellar spherules, made of egg lecithin, stearylamine and cholesterol, are supposed to exert a target effect leading to a greater accumulation of interferon in the liver and spleen. The possible use of liposomes as vectors of interferon in different viral pathologies is discussed."}
{"id": "PMID:208450", "title": "A benign hepatocellular adenoma treated by extended right lobectomy.", "content": "A 19-year-old woman with a large benign hepatocellular adenoma is presented. The initial symptom was continuous anaemia demanding transfusions twice a month. Coeliac angiography revealed the hepatic tumour, which was thought to be malignant. Angiography produced permanent paraplegia as a complication. The tumour was radically removed by an extended right lobectomy. The weight of the operation specimen was 2200 g. Histologically the differential diagnosis layed between benign hepatocellular adenoma and hepatocellular carcinoma. Postoperative stricture of the common duct developed as a complication of T-tube and was successfully treated at reoperation. Liver function became totally restored after the operation and after 5 years' follow-up there has been no tumour recurrence. The very rare benign hepatocellular adenomas are discussed.", "contents": "A benign hepatocellular adenoma treated by extended right lobectomy. A 19-year-old woman with a large benign hepatocellular adenoma is presented. The initial symptom was continuous anaemia demanding transfusions twice a month. Coeliac angiography revealed the hepatic tumour, which was thought to be malignant. Angiography produced permanent paraplegia as a complication. The tumour was radically removed by an extended right lobectomy. The weight of the operation specimen was 2200 g. Histologically the differential diagnosis layed between benign hepatocellular adenoma and hepatocellular carcinoma. Postoperative stricture of the common duct developed as a complication of T-tube and was successfully treated at reoperation. Liver function became totally restored after the operation and after 5 years' follow-up there has been no tumour recurrence. The very rare benign hepatocellular adenomas are discussed."}
{"id": "PMID:208451", "title": "The action of phenytoin on a composite electrical-chemical synapse in the lamprey spinal cord.", "content": "The effect of phenytoin (PTN), 20 microgram per milliliter, was tested on the composite electrical-chemical synapse between pairs of giant interneurons in the isolated spinal cords of river lampreys (Ichthimyzon unicuspis). The main observations were that: (1) PTN reversibly reduced the chemical component of the excitatory postsynaptic potential by up to 70%; (2) PTN greatly reduced or eliminated posttetanic potentiation (PTP) of the chemical component; (3) PTN produced little or no decrease in the size of the electrical component; and (4) PTN did not cause blockage of the electrical component during high-frequency stimulation of the presynaptic neuron. Since the electrical component reflects the presynaptic spike, the suppression of PTP cannot be explained by blockage of this spike during the tetanus. These four observations are consistent with a current hypothesis concerning the anticonvulsant effect of PTN--that the drug inhibits calcium entry into stimulated presynaptic terminals. This would block PTP by reducing the accumulation of calcium in the terminal during repetitive stimulation.", "contents": "The action of phenytoin on a composite electrical-chemical synapse in the lamprey spinal cord. The effect of phenytoin (PTN), 20 microgram per milliliter, was tested on the composite electrical-chemical synapse between pairs of giant interneurons in the isolated spinal cords of river lampreys (Ichthimyzon unicuspis). The main observations were that: (1) PTN reversibly reduced the chemical component of the excitatory postsynaptic potential by up to 70%; (2) PTN greatly reduced or eliminated posttetanic potentiation (PTP) of the chemical component; (3) PTN produced little or no decrease in the size of the electrical component; and (4) PTN did not cause blockage of the electrical component during high-frequency stimulation of the presynaptic neuron. Since the electrical component reflects the presynaptic spike, the suppression of PTP cannot be explained by blockage of this spike during the tetanus. These four observations are consistent with a current hypothesis concerning the anticonvulsant effect of PTN--that the drug inhibits calcium entry into stimulated presynaptic terminals. This would block PTP by reducing the accumulation of calcium in the terminal during repetitive stimulation."}
{"id": "PMID:208452", "title": "The cherry-red spot--myoclonus syndrome.", "content": "Three young women, 2 of them sisters, were found to have cherry-red spots at the macula when they were children. In 1 patient the spots faded before she was 20 years old. In all 3, incapacitating myoclonus and insidious visual loss developed in adolescence. Their intellect is normal and they have no gargoyle-like features. A variety of lysosomal inclusions were noted in cortical neurons in a biopsy specimen taken from 1 patient in childhood. Liver biopsy fifteen years later revealed mucopolysaccharide-like inclusions in Kupffer cells and hepatocytes. Lipofuscin bodies were abundant in neurons and hepatocytes. The patients excrete sialic acid-containing oligosaccharides not present in normal urine, suggesting a defect in degradation of glycoproteins. The specific enzymatic defect in these patients appears to be a deficiency of lysosomal neuraminidase.", "contents": "The cherry-red spot--myoclonus syndrome. Three young women, 2 of them sisters, were found to have cherry-red spots at the macula when they were children. In 1 patient the spots faded before she was 20 years old. In all 3, incapacitating myoclonus and insidious visual loss developed in adolescence. Their intellect is normal and they have no gargoyle-like features. A variety of lysosomal inclusions were noted in cortical neurons in a biopsy specimen taken from 1 patient in childhood. Liver biopsy fifteen years later revealed mucopolysaccharide-like inclusions in Kupffer cells and hepatocytes. Lipofuscin bodies were abundant in neurons and hepatocytes. The patients excrete sialic acid-containing oligosaccharides not present in normal urine, suggesting a defect in degradation of glycoproteins. The specific enzymatic defect in these patients appears to be a deficiency of lysosomal neuraminidase."}
{"id": "PMID:208453", "title": "Perhexiline neuropathy: a clinicopathological study.", "content": "Five patients developed a mild to severe polyneuropathy while under treatment with perhexiline maleate, a drug used in long-term treatment of angina pectoris. Recovery took place within a few months after drug withdrawal. We performed qualitative and quantitative light and electron microscopical studies, including teased fiber preparations, in different patients; 16 to 90% of the fibers showed segmental demyelination, an unusual feature in drug-induced neuropathies, and 3 to 20% were undergoing wallerian degeneration. Severe loss of myelinated axons was noted in all 5 patients. In these patients clinical symptoms occurred only when a great number of fibers had already been lost and most of the surviving fibers showed demyelination.", "contents": "Perhexiline neuropathy: a clinicopathological study. Five patients developed a mild to severe polyneuropathy while under treatment with perhexiline maleate, a drug used in long-term treatment of angina pectoris. Recovery took place within a few months after drug withdrawal. We performed qualitative and quantitative light and electron microscopical studies, including teased fiber preparations, in different patients; 16 to 90% of the fibers showed segmental demyelination, an unusual feature in drug-induced neuropathies, and 3 to 20% were undergoing wallerian degeneration. Severe loss of myelinated axons was noted in all 5 patients. In these patients clinical symptoms occurred only when a great number of fibers had already been lost and most of the surviving fibers showed demyelination."}
{"id": "PMID:208454", "title": "Ectopic generation of impulses and cross-talk in spinal nerve roots of \"dystrophic\" mice.", "content": "In \"dystrophic\" mice, many spinal root axons are bare and closely apposed to one another in midroot. The direction of nerve impulse traffic in lubosacral spinal nerve roots was determined by biphasic recording of spontaneous activity. In normal mice, impulse traffic in dorsal and ventral roots is directed toward and away from the spinal cord, respectively. However, in spinal root fibers of dystrophic mice, impulses also originate in midroot and are propagated toward both the spinal cord and the periphery. Impulses originate in midroot as single isolated events, in bursts at frequencies of up to 100 Hz, or as continuous activity persisting for several minutes in single fibers. Ectopically arising activity in some single fibers is consistently associated with transmission of an impulse in another fiber past the site of  origin of the ectopically arising impulse. Thus impulses arise in the spinal root axons of dystrophic mice both spontaneously and as a result of cross-talk between single fibers.", "contents": "Ectopic generation of impulses and cross-talk in spinal nerve roots of \"dystrophic\" mice. In \"dystrophic\" mice, many spinal root axons are bare and closely apposed to one another in midroot. The direction of nerve impulse traffic in lubosacral spinal nerve roots was determined by biphasic recording of spontaneous activity. In normal mice, impulse traffic in dorsal and ventral roots is directed toward and away from the spinal cord, respectively. However, in spinal root fibers of dystrophic mice, impulses also originate in midroot and are propagated toward both the spinal cord and the periphery. Impulses originate in midroot as single isolated events, in bursts at frequencies of up to 100 Hz, or as continuous activity persisting for several minutes in single fibers. Ectopically arising activity in some single fibers is consistently associated with transmission of an impulse in another fiber past the site of  origin of the ectopically arising impulse. Thus impulses arise in the spinal root axons of dystrophic mice both spontaneously and as a result of cross-talk between single fibers."}
{"id": "PMID:208455", "title": "Circular polarization of luminescence: biochemical and biophysical applications.", "content": "The circular polarization of the luminescence of a chromophore is one of the manifestations of its chirality. As such, CPL has the potential of probing molecular conformation, which has a tight relationship to molecular chirality. CPL has characteristic features that make it specifically useful as a tool for the investigation of conformational problems under the proper circumstances: it is related to the molecular conformation in the electronically excited state; it is specific to the luminescent chromophores when different kinds are present in the system studied; the number of electronic transitions involved are relatively few in number, often one per chromophore, thus simplifying the interpretation of the spectra; forbidden transitions are amenable to study by CPL; and CPL permits the study of the optical activity of oriented systems by simple means. The systems tackled by CPL range from small to giant molecules, which illustrates its wide applicability. Naturally, like any other research tool, CPL has limitations as to the questions to which it can be addressed and the systems that can benefit from its services (e.g. they should not be photosensitive; they should, of course, be luminescent; and they should yield measurable signals). However, for the proper questions and suitable systems it has been found to be of tremendous help.", "contents": "Circular polarization of luminescence: biochemical and biophysical applications. The circular polarization of the luminescence of a chromophore is one of the manifestations of its chirality. As such, CPL has the potential of probing molecular conformation, which has a tight relationship to molecular chirality. CPL has characteristic features that make it specifically useful as a tool for the investigation of conformational problems under the proper circumstances: it is related to the molecular conformation in the electronically excited state; it is specific to the luminescent chromophores when different kinds are present in the system studied; the number of electronic transitions involved are relatively few in number, often one per chromophore, thus simplifying the interpretation of the spectra; forbidden transitions are amenable to study by CPL; and CPL permits the study of the optical activity of oriented systems by simple means. The systems tackled by CPL range from small to giant molecules, which illustrates its wide applicability. Naturally, like any other research tool, CPL has limitations as to the questions to which it can be addressed and the systems that can benefit from its services (e.g. they should not be photosensitive; they should, of course, be luminescent; and they should yield measurable signals). However, for the proper questions and suitable systems it has been found to be of tremendous help."}
{"id": "PMID:208459", "title": "5,6-Dihydro-5-azathymidine: in vitro antiviral properties against human herpesviruses.", "content": "5,6-Dihydro-5-azathymidine (DHAdT), a novel water-soluble nucleoside antibiotic, inhibits herpes simplex virus type 1 (HSV-1) in appropriately infected cell cultures to a greater extent than herpes simplex virus type 2 (HSV-2). Vaccinia virus was less susceptible than HSV-2, and pseudorabies virus yields were not reduced at the concentrations studied. Plaque formation by varicella-zoster virus was suppressed by DHAdT. DHAdT was slightly toxic to cells at concentrations that were inhibitory for HSV-1 and varicella-zoster virus. Thymidine and deoxyuridine completely reversed the anti-HSV-1 activity of DHAdT, whereas deoxycytidine was partially effective. Compared with other nucleoside analogs with activity for HSV-1, DHAdT was less active than 5-iodo-2'-deoxyuridine or 1-beta-d-arabinofuranosylcytosine and nearly equipotent with 9-beta-d-arabinofuranosyladenine.", "contents": "5,6-Dihydro-5-azathymidine: in vitro antiviral properties against human herpesviruses. 5,6-Dihydro-5-azathymidine (DHAdT), a novel water-soluble nucleoside antibiotic, inhibits herpes simplex virus type 1 (HSV-1) in appropriately infected cell cultures to a greater extent than herpes simplex virus type 2 (HSV-2). Vaccinia virus was less susceptible than HSV-2, and pseudorabies virus yields were not reduced at the concentrations studied. Plaque formation by varicella-zoster virus was suppressed by DHAdT. DHAdT was slightly toxic to cells at concentrations that were inhibitory for HSV-1 and varicella-zoster virus. Thymidine and deoxyuridine completely reversed the anti-HSV-1 activity of DHAdT, whereas deoxycytidine was partially effective. Compared with other nucleoside analogs with activity for HSV-1, DHAdT was less active than 5-iodo-2'-deoxyuridine or 1-beta-d-arabinofuranosylcytosine and nearly equipotent with 9-beta-d-arabinofuranosyladenine."}
{"id": "PMID:208460", "title": "Inactivation of herpes simplex viruses by nonionic surfactants.", "content": "Nonionic surface-active agents possessing ether or amide linkages between the hydrophillic and hydrophobic portions of the molecule rapidly inactivated the infectivity of herpes simplex viruses. The activity stemmed from the ability of nonionic surfactants to dissolve lipid-containing membranes. This was confirmed by observing surfactant destruction of mammalian cell plasma membranes and herpes simplex virus envelopes. Proprietary vaginal contraceptive formulations containing nonionic surfactants also inactivated herpes simplex virus infectivity. This observation suggests that nonionic surfactants in appropriate formulation could effectively prevent herpes simplex virus transmission.", "contents": "Inactivation of herpes simplex viruses by nonionic surfactants. Nonionic surface-active agents possessing ether or amide linkages between the hydrophillic and hydrophobic portions of the molecule rapidly inactivated the infectivity of herpes simplex viruses. The activity stemmed from the ability of nonionic surfactants to dissolve lipid-containing membranes. This was confirmed by observing surfactant destruction of mammalian cell plasma membranes and herpes simplex virus envelopes. Proprietary vaginal contraceptive formulations containing nonionic surfactants also inactivated herpes simplex virus infectivity. This observation suggests that nonionic surfactants in appropriate formulation could effectively prevent herpes simplex virus transmission."}
{"id": "PMID:208461", "title": "Effect of zinc and other chemical agents on foot-and-mouth-disease virus replication.", "content": "Chemical agents reported to inhibit the growth of various ribonucleic acid and deoxyribonucleic acid viruses were tested against foot-and-mouth disease virus in cell culture. These included Zn(2+), aurintricarboxylic acid, polyribocytidylic acid, polyriboinosinic acid, phosphonoacetic acid, and the viral contact inactivator N-methyl isatin beta-thiosemicarbazone alone and with CuSO(4). The most effective agent, Zn(2+), inhibited foot-and-mouth disease virus production in primary calf kidney cells by 1 log unit at 0.05 mM Zn(2+) and completely at 0.50 mM. Zinc was inhibitory even when added late in infection and was nontoxic to uninfected cells as measured by protein and nucleic acid syntheses. Polyacrylamide gel patterns of [(35)S]methionine-labeled, virus-specific proteins showed increasing amounts of higher-molecular-weight material, in accord with reports that Zn(2+) inhibits post-translational cleavages of other picornavirus precursor polypeptides.", "contents": "Effect of zinc and other chemical agents on foot-and-mouth-disease virus replication. Chemical agents reported to inhibit the growth of various ribonucleic acid and deoxyribonucleic acid viruses were tested against foot-and-mouth disease virus in cell culture. These included Zn(2+), aurintricarboxylic acid, polyribocytidylic acid, polyriboinosinic acid, phosphonoacetic acid, and the viral contact inactivator N-methyl isatin beta-thiosemicarbazone alone and with CuSO(4). The most effective agent, Zn(2+), inhibited foot-and-mouth disease virus production in primary calf kidney cells by 1 log unit at 0.05 mM Zn(2+) and completely at 0.50 mM. Zinc was inhibitory even when added late in infection and was nontoxic to uninfected cells as measured by protein and nucleic acid syntheses. Polyacrylamide gel patterns of [(35)S]methionine-labeled, virus-specific proteins showed increasing amounts of higher-molecular-weight material, in accord with reports that Zn(2+) inhibits post-translational cleavages of other picornavirus precursor polypeptides."}
{"id": "PMID:208462", "title": "Treatment with levamisole of recurrent herpes genitalis.", "content": "A double-blind study was carried out to investigate the possibility of therapeutic effect of levamisole on recurrent progenital herpes. One hundred and nine patients, including 53 females, entered the study, but only 75 completed. Levamisole, 50 mg three times daily for 3 days, was started at the first sign of recurrence. The study period consisted of 6 visits or 12 months, whichever came first. No statistical differences were observed between levamisole and placebo groups when comparing the duration of the lesion and the degree of pain, although less pain was observed among those on levamisole. The interval between attacks was increasingly prolonged in the levamisole-treated group, and reached a significant level at the sixth visit. However, analysis on the basis of mean cumulative number of days between attacks showed no significant differences throughout the study period. Because of occasional neutropenia and generalized urticaria, and because of the absence of clear-cut clinical improvement of statistical significance, levamisole was considered of limited benefit to patients with recurrent genital herpes infection.", "contents": "Treatment with levamisole of recurrent herpes genitalis. A double-blind study was carried out to investigate the possibility of therapeutic effect of levamisole on recurrent progenital herpes. One hundred and nine patients, including 53 females, entered the study, but only 75 completed. Levamisole, 50 mg three times daily for 3 days, was started at the first sign of recurrence. The study period consisted of 6 visits or 12 months, whichever came first. No statistical differences were observed between levamisole and placebo groups when comparing the duration of the lesion and the degree of pain, although less pain was observed among those on levamisole. The interval between attacks was increasingly prolonged in the levamisole-treated group, and reached a significant level at the sixth visit. However, analysis on the basis of mean cumulative number of days between attacks showed no significant differences throughout the study period. Because of occasional neutropenia and generalized urticaria, and because of the absence of clear-cut clinical improvement of statistical significance, levamisole was considered of limited benefit to patients with recurrent genital herpes infection."}
{"id": "PMID:208463", "title": "Isolation and characterization of multiply antibiotic-resistant Clostridum perfringens strains from porcine feces.", "content": "Multiply antibiotic-resistant strains of Clostridium perfringens were isolated from porcine feces. Strains that were resistant to tetracycline, erythromycin, clindamycin, and lincomycin were isolated, but no penicillin- or chloramphenicol-resistant strains were obtained. Typical minimal inhibitory concentrations for resistant strains were 16 to 64 mug of tetracycline per ml, 64 to >128 mug of erythromycin per ml, >/=128 mug of lincomycin per ml, and 16 to 128 mug of clindamycin per ml. Resistance to erythromycin was always associated with resistance to lincomycin and clindamycin. Minimal inhibitory concentrations were determined for 258 strains from six farms that used antibiotics in their feeds and 240 strains from five farms that did not use antibiotics. The results show that 77.9 and 22.7% of the strains from the former farms were resistant to tetracycline and erythromycin-clindamycin-lincomycin, respectively. The comparable data from the latter farms were 25.0 and 0.8%, respectively. Agarose gel electrophoresis failed to reveal a plasmid band that was common to the resistant strains but absent in the susceptible strains. Attempts to transfer tetracycline, erythromycin, and clindamycin resistance from one strain, CW459, were not successful. Antibiotic-susceptible mutants were not isolated from this strain, despite the use of a variety of curing agents.", "contents": "Isolation and characterization of multiply antibiotic-resistant Clostridum perfringens strains from porcine feces. Multiply antibiotic-resistant strains of Clostridium perfringens were isolated from porcine feces. Strains that were resistant to tetracycline, erythromycin, clindamycin, and lincomycin were isolated, but no penicillin- or chloramphenicol-resistant strains were obtained. Typical minimal inhibitory concentrations for resistant strains were 16 to 64 mug of tetracycline per ml, 64 to >128 mug of erythromycin per ml, >/=128 mug of lincomycin per ml, and 16 to 128 mug of clindamycin per ml. Resistance to erythromycin was always associated with resistance to lincomycin and clindamycin. Minimal inhibitory concentrations were determined for 258 strains from six farms that used antibiotics in their feeds and 240 strains from five farms that did not use antibiotics. The results show that 77.9 and 22.7% of the strains from the former farms were resistant to tetracycline and erythromycin-clindamycin-lincomycin, respectively. The comparable data from the latter farms were 25.0 and 0.8%, respectively. Agarose gel electrophoresis failed to reveal a plasmid band that was common to the resistant strains but absent in the susceptible strains. Attempts to transfer tetracycline, erythromycin, and clindamycin resistance from one strain, CW459, were not successful. Antibiotic-susceptible mutants were not isolated from this strain, despite the use of a variety of curing agents."}
{"id": "PMID:208469", "title": "Giant cell tumor of the tendon sheath involving skin.", "content": "Giant cell tumor of the tendon sheath is the second most common tumor of the fingers and hands but is only rarely mentioned in the dermatologic literature. Although its pathogenesis has been debated, it is probably a type of fibrous histiocytoma. This tumor is almost always benign but may locally invade the overlying dermis and be confused with a malignant neoplasms. It often extends to the synovium of the adjacent joint space and necessitates total excision to prevent local recurrence. Therefore, excision should be undertaken by a physican who is surgically qualified for such procedure. We report a case that illustrates the clinical and pathologic aspects of this lesion.", "contents": "Giant cell tumor of the tendon sheath involving skin. Giant cell tumor of the tendon sheath is the second most common tumor of the fingers and hands but is only rarely mentioned in the dermatologic literature. Although its pathogenesis has been debated, it is probably a type of fibrous histiocytoma. This tumor is almost always benign but may locally invade the overlying dermis and be confused with a malignant neoplasms. It often extends to the synovium of the adjacent joint space and necessitates total excision to prevent local recurrence. Therefore, excision should be undertaken by a physican who is surgically qualified for such procedure. We report a case that illustrates the clinical and pathologic aspects of this lesion."}
{"id": "PMID:208472", "title": "Male breast cancer: a clinicopathologic study of 97 cases.", "content": "From 1949 through 1976, 97 men have been treated at Memorial Hospital for primary operable breast cancer. Seven per cent had intraductal carcinoma. Of the patients with invasive carcinoma 30% were pathologic stage I, 54% stage II, and 16% stage III. Fourty-six per cent had pathologically negative axillary lymph nodes. The most common type of tumor was infiltrating duct carcinoma. Fourty per cent of the patients had microscopic gynecomastia. None of the eight patients with intraductal or intracystic carcinoma died of cancer. Survival of the entire group of men with invasive carcinoma was 40% after ten years. The ten year survival for men with negative nodes was 79%, for men with positive nodes 11%. Comparison with a series of 304 women with breast cancer operated on at Memorial Hospital in 1960 revealed no difference with regard to incidence of positive axillary lymph nodes or stage of disease. There was, however, a significantly lower survival rate for men. This poorer prognosis was limited to those men with pathologically positive axillary nodes.", "contents": "Male breast cancer: a clinicopathologic study of 97 cases. From 1949 through 1976, 97 men have been treated at Memorial Hospital for primary operable breast cancer. Seven per cent had intraductal carcinoma. Of the patients with invasive carcinoma 30% were pathologic stage I, 54% stage II, and 16% stage III. Fourty-six per cent had pathologically negative axillary lymph nodes. The most common type of tumor was infiltrating duct carcinoma. Fourty per cent of the patients had microscopic gynecomastia. None of the eight patients with intraductal or intracystic carcinoma died of cancer. Survival of the entire group of men with invasive carcinoma was 40% after ten years. The ten year survival for men with negative nodes was 79%, for men with positive nodes 11%. Comparison with a series of 304 women with breast cancer operated on at Memorial Hospital in 1960 revealed no difference with regard to incidence of positive axillary lymph nodes or stage of disease. There was, however, a significantly lower survival rate for men. This poorer prognosis was limited to those men with pathologically positive axillary nodes."}
{"id": "PMID:208473", "title": "The immunological response of Nigerian infants to attenuated and inactivated poliovaccines.", "content": "A comparison was made of the immunity conferred by injected formalin-killed poliomyelitis vaccine and orally administered attenuated poliomyelitis vaccine in Nigerian infants under tropical conditions where interfering enteroviruses have caused poor conversion rates with attenuated poliomyelitis vaccine. Two hundred and thirty infants completed the immunization schedules. The levels of antibodies to polioviruses were assessed before immunization and at periodic intervals during the trial. Seventy-four per cent, 72% and 85% of the children lacked antibodies to poliovirus types 1, 2 and 3 respectively at 6 months if they received no vaccine, the comparative proportions respectively were 52%, 8% and 48% if they had oral attenuated poliovaccine and 2%, 4% and 0% if they had three doses of inactivated poliovaccine. It is suggested that killed poliovaccine incorporated in a quadruple vaccine may have a place in developing countries like Nigeria in the control of diphtheria, tetanus, whooping cough and poliomyelitis.", "contents": "The immunological response of Nigerian infants to attenuated and inactivated poliovaccines. A comparison was made of the immunity conferred by injected formalin-killed poliomyelitis vaccine and orally administered attenuated poliomyelitis vaccine in Nigerian infants under tropical conditions where interfering enteroviruses have caused poor conversion rates with attenuated poliomyelitis vaccine. Two hundred and thirty infants completed the immunization schedules. The levels of antibodies to polioviruses were assessed before immunization and at periodic intervals during the trial. Seventy-four per cent, 72% and 85% of the children lacked antibodies to poliovirus types 1, 2 and 3 respectively at 6 months if they received no vaccine, the comparative proportions respectively were 52%, 8% and 48% if they had oral attenuated poliovaccine and 2%, 4% and 0% if they had three doses of inactivated poliovaccine. It is suggested that killed poliovaccine incorporated in a quadruple vaccine may have a place in developing countries like Nigeria in the control of diphtheria, tetanus, whooping cough and poliomyelitis."}
{"id": "PMID:208474", "title": "Tracheal tumors: surgical management.", "content": "In a 15-year period, 63 patients with primary tracheal tumors were seen. Twenty-eight patients with primary tumors and 8 with secondary tumors of the trachea were treated by resection with single-stage reconstruction. There were 24 cylindrical resections of trachea, 2 lateral resections of trachea, and 10 carinal reconstructions. Thirty-five additional patients with primary tracheal tumors were managed by staged reconstruction, irradiation, or no treatment. The most common primary lesion was squamous cell carcinoma and the second, adenoid cystic carcinoma. Benign primary tumors and low-grade malignant tumors obtained excellent palliation and usually cure. Surgical removal of squamous cell carcinoma and adenoid cystic carcinoma, usually with adjunctive irradiation, provided good palliation or the probability of cure. Resection of selected secondary tumors provided long-term palliation.", "contents": "Tracheal tumors: surgical management. In a 15-year period, 63 patients with primary tracheal tumors were seen. Twenty-eight patients with primary tumors and 8 with secondary tumors of the trachea were treated by resection with single-stage reconstruction. There were 24 cylindrical resections of trachea, 2 lateral resections of trachea, and 10 carinal reconstructions. Thirty-five additional patients with primary tracheal tumors were managed by staged reconstruction, irradiation, or no treatment. The most common primary lesion was squamous cell carcinoma and the second, adenoid cystic carcinoma. Benign primary tumors and low-grade malignant tumors obtained excellent palliation and usually cure. Surgical removal of squamous cell carcinoma and adenoid cystic carcinoma, usually with adjunctive irradiation, provided good palliation or the probability of cure. Resection of selected secondary tumors provided long-term palliation."}
{"id": "PMID:208480", "title": "Subacute phenytoin intoxication syndrome.", "content": "Phenytoin sodium intoxication of subacute onset may occur in cases of nonepileptic patients who receive phenytoin for suppression of cardiac arrhythmias. The case reported here is of a syndrome that consisted of dementia, cerebellar dysfunction, and peripheral neuropathy. Withdrawal of phenytoin was followed by a slow improvement in the syndrome. Awareness of the features of subacute phenytoin intoxication in cardiac patients is important because this entity may mimic cerebrovascular disease. Periodic monitoring of serum phenytoin concentrations is advisable.", "contents": "Subacute phenytoin intoxication syndrome. Phenytoin sodium intoxication of subacute onset may occur in cases of nonepileptic patients who receive phenytoin for suppression of cardiac arrhythmias. The case reported here is of a syndrome that consisted of dementia, cerebellar dysfunction, and peripheral neuropathy. Withdrawal of phenytoin was followed by a slow improvement in the syndrome. Awareness of the features of subacute phenytoin intoxication in cardiac patients is important because this entity may mimic cerebrovascular disease. Periodic monitoring of serum phenytoin concentrations is advisable."}
{"id": "PMID:208479", "title": "Effect of lithium chloride on electrically stimulated guinea-pig longitudinal muscle-myenteric plexus.", "content": "Lithium chloride, in the concentration range of 10(-4)M to 10(-2)M, increases the height of electrically induced contractions of guinea-pig longitudinal muscle-myenteric plexus preparation. Higher concentrations of the salt cause a progressive block of contractions. Sodium chloride shows no augmentation of contraction height, but concentrations above 10(-2)M only cause block of contractions. Inhibition of contractions by LiCl exactly parallels inhibition of responses of the tissue to exogenous acetylcholine (ACh); thus, the site of action is considered to be directly on the muscle. Sodium chloride causes insignificant inhibition of responses to exogenous ACh. Guinea-pigs injected chronically with high doses of LiCl (2 months, 5 mEq/kg show no stimulatory effect on LiCl in vitro, only inhibition. This finding suggests that tolerance to at least some of the actions of LiCl may occur upon chronic administration, particularly if the dose used is very high.", "contents": "Effect of lithium chloride on electrically stimulated guinea-pig longitudinal muscle-myenteric plexus. Lithium chloride, in the concentration range of 10(-4)M to 10(-2)M, increases the height of electrically induced contractions of guinea-pig longitudinal muscle-myenteric plexus preparation. Higher concentrations of the salt cause a progressive block of contractions. Sodium chloride shows no augmentation of contraction height, but concentrations above 10(-2)M only cause block of contractions. Inhibition of contractions by LiCl exactly parallels inhibition of responses of the tissue to exogenous acetylcholine (ACh); thus, the site of action is considered to be directly on the muscle. Sodium chloride causes insignificant inhibition of responses to exogenous ACh. Guinea-pigs injected chronically with high doses of LiCl (2 months, 5 mEq/kg show no stimulatory effect on LiCl in vitro, only inhibition. This finding suggests that tolerance to at least some of the actions of LiCl may occur upon chronic administration, particularly if the dose used is very high."}
{"id": "PMID:208481", "title": "Pathogenesis of Marek's disease in chickens with maternal antibody.", "content": "Histopathological lesions were studied in chickens with maternal antibody against MD virus at 14-day intervals after their exposure by contact to HPRS-16 of MD virus in the first-day of life. The first lesions occured 14 days after infection in the liver, kidney, heart, brain and the sciatic nerves. Relatively, the most expressive changes were observed between 56th and 70th day after infection. Lesions were characterized as light to heavy infiltrations formed by immature and mature pleomorphic mononuclear cells. Among these cells myeloid type cells occured too. In some cases expressive tumorous lesions with intensive mitosis were observed mainly in the liver. Intranuclear inclusion bodies were also observed mainly among the proliferating epithelial cells of the proventriculus. 14-days after infection changes in the brain were classified as nonpurulenta encephalitis. Gross lesions characteristic of MD occured the most frequently in the gonads, liver and the kidney. In one case 56 days after infection herpesvirus-like particles were observed by electron microscopy in the tumorous gonads and liver. They measured about 200 to 260 nm in diameter. Degraded and/or aberrant incompleted virus-like particles occured the most often and completed (enveloped) ones with electrondense nucleoids were observed occasionally. It was concluded that MD in chickens with materanal antibody against MD virus shows monophasis progress.", "contents": "Pathogenesis of Marek's disease in chickens with maternal antibody. Histopathological lesions were studied in chickens with maternal antibody against MD virus at 14-day intervals after their exposure by contact to HPRS-16 of MD virus in the first-day of life. The first lesions occured 14 days after infection in the liver, kidney, heart, brain and the sciatic nerves. Relatively, the most expressive changes were observed between 56th and 70th day after infection. Lesions were characterized as light to heavy infiltrations formed by immature and mature pleomorphic mononuclear cells. Among these cells myeloid type cells occured too. In some cases expressive tumorous lesions with intensive mitosis were observed mainly in the liver. Intranuclear inclusion bodies were also observed mainly among the proliferating epithelial cells of the proventriculus. 14-days after infection changes in the brain were classified as nonpurulenta encephalitis. Gross lesions characteristic of MD occured the most frequently in the gonads, liver and the kidney. In one case 56 days after infection herpesvirus-like particles were observed by electron microscopy in the tumorous gonads and liver. They measured about 200 to 260 nm in diameter. Degraded and/or aberrant incompleted virus-like particles occured the most often and completed (enveloped) ones with electrondense nucleoids were observed occasionally. It was concluded that MD in chickens with materanal antibody against MD virus shows monophasis progress."}
{"id": "PMID:208482", "title": "[Comparative studies on the virulence of strains of Aujeszky's disease virus].", "content": "Comparative Studies on Virulence of Aujeszky's Disease Virus Strains Clinical, virological, pathomorphological and immunofluorescence examinations were performed in 24 piglets, 4 of them being experimentally infected with a virulent (B) and 6 of them with a low virulent virus strain of Aujeszky's disease (K). 14 animals were kept in enzootically infected practice stock for contact exposure. Results revealed differences in clinical and morphological signs of the disease in several experimental groups due to different virulence and tissue tropism of the used virus strains. Piglets infected with strain B showed clinical changes characteristic for the disease. In animals infected with strain K no clinical signs could be observed in the same observation period. In contact animals only respiratory disorders occurred. Histological changes of the central nervous system were established in animals of all experimental groups. In animals infected with strain K and in the contact animals in addition there were ascertained morphological changes of the interstice of the lungs in form of interstitial pneumonia of the lymphohistiocytic types. Low virulent strains are proved to show a distinct pneumotropism.", "contents": "[Comparative studies on the virulence of strains of Aujeszky's disease virus]. Comparative Studies on Virulence of Aujeszky's Disease Virus Strains Clinical, virological, pathomorphological and immunofluorescence examinations were performed in 24 piglets, 4 of them being experimentally infected with a virulent (B) and 6 of them with a low virulent virus strain of Aujeszky's disease (K). 14 animals were kept in enzootically infected practice stock for contact exposure. Results revealed differences in clinical and morphological signs of the disease in several experimental groups due to different virulence and tissue tropism of the used virus strains. Piglets infected with strain B showed clinical changes characteristic for the disease. In animals infected with strain K no clinical signs could be observed in the same observation period. In contact animals only respiratory disorders occurred. Histological changes of the central nervous system were established in animals of all experimental groups. In animals infected with strain K and in the contact animals in addition there were ascertained morphological changes of the interstice of the lungs in form of interstitial pneumonia of the lymphohistiocytic types. Low virulent strains are proved to show a distinct pneumotropism."}
{"id": "PMID:208486", "title": "Intranuclear crystal formation in picornavirus-infected cells.", "content": "Cells infected with echovirus or poliovirus were incubated at a suboptimal temperature (28 degrees C). When the cells were examined by electron microscopy, not only were crystalline arrays of mature virus particles observed in the cytoplasm but crystals composed of immature virus-like particles were also evident in the less electron-dense central region of the nucleus. Immunofluorescent and autoradiographic studies revealed the presence of viral proteins and RNA in the nucleus. These findings strongly suggest that the intranuclear crystals are composed of incomplete virus particles and that crystal formation at such a low temperature may be a remarkable feature common to picornaviruses. Possible mechanisms for the intranuclear synthesis of viral constituents are discussed.", "contents": "Intranuclear crystal formation in picornavirus-infected cells. Cells infected with echovirus or poliovirus were incubated at a suboptimal temperature (28 degrees C). When the cells were examined by electron microscopy, not only were crystalline arrays of mature virus particles observed in the cytoplasm but crystals composed of immature virus-like particles were also evident in the less electron-dense central region of the nucleus. Immunofluorescent and autoradiographic studies revealed the presence of viral proteins and RNA in the nucleus. These findings strongly suggest that the intranuclear crystals are composed of incomplete virus particles and that crystal formation at such a low temperature may be a remarkable feature common to picornaviruses. Possible mechanisms for the intranuclear synthesis of viral constituents are discussed."}
{"id": "PMID:208487", "title": "Syncytium formation caused by human cytomegalovirus in human embryonic lung fibroblasts.", "content": "Large syncytia were regularly produced after prolonged infection in vitro of human embryonic fibroblasts by AD169 and other strains of human CMV. The syncytia showed typical CMV intranuclear inclusion bodies and herpesvirus particles in the nuclei and cytoplasm. It is proposed that syncytium formation follows abortive infection of the fibroblasts with defective virus.", "contents": "Syncytium formation caused by human cytomegalovirus in human embryonic lung fibroblasts. Large syncytia were regularly produced after prolonged infection in vitro of human embryonic fibroblasts by AD169 and other strains of human CMV. The syncytia showed typical CMV intranuclear inclusion bodies and herpesvirus particles in the nuclei and cytoplasm. It is proposed that syncytium formation follows abortive infection of the fibroblasts with defective virus."}
{"id": "PMID:208488", "title": "Ribonuclease activities associated with purified foot and mouth disease virus.", "content": "Ribonuclease activities internally and externally associated with purified foot-and mouth disease virus were detected. The outer activity was easily removed by cesium chloride or by detergent (Sarkosyl). The inner activity is not removable by any procedure used and could be the enzyme responsible for the heterogeneity normally observed in the extracted FMDV-RNA. It is not known at present if both activities are related to the same or to different enzymes.", "contents": "Ribonuclease activities associated with purified foot and mouth disease virus. Ribonuclease activities internally and externally associated with purified foot-and mouth disease virus were detected. The outer activity was easily removed by cesium chloride or by detergent (Sarkosyl). The inner activity is not removable by any procedure used and could be the enzyme responsible for the heterogeneity normally observed in the extracted FMDV-RNA. It is not known at present if both activities are related to the same or to different enzymes."}
{"id": "PMID:208489", "title": "Latent herpes simplex virus in ganglia of mice after primary infection and reinoculation at a distant site.", "content": "Herpes simplex virus (HSV)-infected hairless mice with evidence of latent infection in spinal ganglia did not develop latent HSV infections in trigeminal ganglia upon reinfection in the oro-facial area. HSV-infected and PAA-treated mice without evidence of latent HSV infection in spinal ganglia were resistant to reinfection in the lumbar region, but not to that performed in the oro-facial area.", "contents": "Latent herpes simplex virus in ganglia of mice after primary infection and reinoculation at a distant site. Herpes simplex virus (HSV)-infected hairless mice with evidence of latent infection in spinal ganglia did not develop latent HSV infections in trigeminal ganglia upon reinfection in the oro-facial area. HSV-infected and PAA-treated mice without evidence of latent HSV infection in spinal ganglia were resistant to reinfection in the lumbar region, but not to that performed in the oro-facial area."}
{"id": "PMID:208490", "title": "Interferon enhances T cell mediated cytotoxicity of H-2 compatible target cells infected with UV-inactivated herpes simplex virus.", "content": "Mouse L-cells infected with UV-inactivated HSV could serve as suitable targets for monitoring H-2 restricted cytotoxicity mediated by HSV-immune T cells. Cytotoxic potential of immune T cells for H-2 compatible targets exposed to UV-inactivated HSV was enhanced if the later were pretreated with mouse interferon.", "contents": "Interferon enhances T cell mediated cytotoxicity of H-2 compatible target cells infected with UV-inactivated herpes simplex virus. Mouse L-cells infected with UV-inactivated HSV could serve as suitable targets for monitoring H-2 restricted cytotoxicity mediated by HSV-immune T cells. Cytotoxic potential of immune T cells for H-2 compatible targets exposed to UV-inactivated HSV was enhanced if the later were pretreated with mouse interferon."}
{"id": "PMID:208491", "title": "Analysis of poliovirus antibody complexes by density gradient centrifugation.", "content": "Analysis of poliovirus antibody complexes by sucrose density gradient centrifugation demonstrated differences in behavior of sensitized virus between early and late serum, particularly with regard to neutralizing capacity of different concentrations of antiserum.", "contents": "Analysis of poliovirus antibody complexes by density gradient centrifugation. Analysis of poliovirus antibody complexes by sucrose density gradient centrifugation demonstrated differences in behavior of sensitized virus between early and late serum, particularly with regard to neutralizing capacity of different concentrations of antiserum."}
{"id": "PMID:208492", "title": "Detection of Mason-Pfizer monkey virus infection by syncytia formation of human cells doubly transformed by Rous sarcoma virus and simian virus 40.", "content": "Human cells doubly transformed by Rous sarcoma virus and SV40 (RSb cells) formed syncytia by cocultivation with Mason-Pfizer monkey virus (MPMV)-producing cells. This cell fusion was blocked by anti-MPMV serum indicating that the phenomenon is MPMV specific. The RSb cells were successfully used for MPMV infectivity assay in the same manner as KC cells.", "contents": "Detection of Mason-Pfizer monkey virus infection by syncytia formation of human cells doubly transformed by Rous sarcoma virus and simian virus 40. Human cells doubly transformed by Rous sarcoma virus and SV40 (RSb cells) formed syncytia by cocultivation with Mason-Pfizer monkey virus (MPMV)-producing cells. This cell fusion was blocked by anti-MPMV serum indicating that the phenomenon is MPMV specific. The RSb cells were successfully used for MPMV infectivity assay in the same manner as KC cells."}
{"id": "PMID:208493", "title": "Inactivation of human cytomegalovirus by phytohemagglutinin.", "content": "Human cytomegalovirus (CMV) was inactivated by treatment with phytohemagglutinin (PHA) in contrast to herpes simplex virus (HSV), which was not. Approximately 90% of infectivity was lost following exposure of CMV to PHA. Greater reduction of infectivity, more than 99%, was obtained following pretreatment of cells with PHA than by direct mixture of the virus and the lectin. Protection of cells was still observed 48 hours after pretreatment of cells with PHA. No difference was found in sensitivity to PHA with 3 strains of CMV tested. PHA preparations from different sources were almost equally effective in inactivation of CMV, whereas leucoagglutinin had minimal effect. Our data suggest that the site of action of PHA occurs at the step(s) of penetration and/or uncoating. Resistance of CMV to trypsin was confirmed, and the enzyme had no effect on sensitivity to lectins.", "contents": "Inactivation of human cytomegalovirus by phytohemagglutinin. Human cytomegalovirus (CMV) was inactivated by treatment with phytohemagglutinin (PHA) in contrast to herpes simplex virus (HSV), which was not. Approximately 90% of infectivity was lost following exposure of CMV to PHA. Greater reduction of infectivity, more than 99%, was obtained following pretreatment of cells with PHA than by direct mixture of the virus and the lectin. Protection of cells was still observed 48 hours after pretreatment of cells with PHA. No difference was found in sensitivity to PHA with 3 strains of CMV tested. PHA preparations from different sources were almost equally effective in inactivation of CMV, whereas leucoagglutinin had minimal effect. Our data suggest that the site of action of PHA occurs at the step(s) of penetration and/or uncoating. Resistance of CMV to trypsin was confirmed, and the enzyme had no effect on sensitivity to lectins."}
{"id": "PMID:208494", "title": "Polyneuropathy in Waldenstr\u00f6m's macroglobulinemia. Deposition of M component on myelin sheaths.", "content": "A chronic sensory neuropathy was the initial symptom in a case of Waldenstr\u00f6m's macroglobulinemia in a 53-year-old woman. Ultrastructural analysis of a biopsied peripheral nerve revealed a modification of the lamellar structure of the myelin sheath. Immunofluorescent microscopy showed IgM-positive deposits on the myelin sheath. The monoclonal globulin (M component) present in the myelin appears to be a causative factor in the neuropathy.", "contents": "Polyneuropathy in Waldenstr\u00f6m's macroglobulinemia. Deposition of M component on myelin sheaths. A chronic sensory neuropathy was the initial symptom in a case of Waldenstr\u00f6m's macroglobulinemia in a 53-year-old woman. Ultrastructural analysis of a biopsied peripheral nerve revealed a modification of the lamellar structure of the myelin sheath. Immunofluorescent microscopy showed IgM-positive deposits on the myelin sheath. The monoclonal globulin (M component) present in the myelin appears to be a causative factor in the neuropathy."}
{"id": "PMID:208495", "title": "Late adult-onset metachromatic leukodystrophy. Dementia and polyneuropathy in a 63-year-old man.", "content": "A diagnosis of adult-onset metachromatic leukodystrophy (MLD) was established in a living 63-year-old man with progressive dementia and peripheral neuropathy. Decreased nerve conduction velocities and elevated spinal fluid protein concentration led to more specific diagnostic studies required to confirm the diagnosis. This case expands the spectrum of adult-onset MLD to patients with dementia and polyneuropathy past the sixth decade of life. Measurement of nerve conduction velocities may help to uncover cases of adult-onset MLD and should be included in the evaluation of dementia.", "contents": "Late adult-onset metachromatic leukodystrophy. Dementia and polyneuropathy in a 63-year-old man. A diagnosis of adult-onset metachromatic leukodystrophy (MLD) was established in a living 63-year-old man with progressive dementia and peripheral neuropathy. Decreased nerve conduction velocities and elevated spinal fluid protein concentration led to more specific diagnostic studies required to confirm the diagnosis. This case expands the spectrum of adult-onset MLD to patients with dementia and polyneuropathy past the sixth decade of life. Measurement of nerve conduction velocities may help to uncover cases of adult-onset MLD and should be included in the evaluation of dementia."}
{"id": "PMID:208496", "title": "Optic nerve head involvement with cytomegalovirus in an adult with lymphoma.", "content": "An optic nerve swelling that was thought clinically to represent a lymphomatous infiltrate of the nerve head developed in a 51-year-old man with histiocytic lymphoma. Histologic examination of the eyes showed the presence of cytomegalovirus (CMV) in the nerve head, but no lymphoma cells. Tru lymphomatous invasion of the nerve head in systemic lymphoma is probably very rare. This case points out an unusual manifestation of adult CMV infection, and a new concern in patients with compromised immune systems.", "contents": "Optic nerve head involvement with cytomegalovirus in an adult with lymphoma. An optic nerve swelling that was thought clinically to represent a lymphomatous infiltrate of the nerve head developed in a 51-year-old man with histiocytic lymphoma. Histologic examination of the eyes showed the presence of cytomegalovirus (CMV) in the nerve head, but no lymphoma cells. Tru lymphomatous invasion of the nerve head in systemic lymphoma is probably very rare. This case points out an unusual manifestation of adult CMV infection, and a new concern in patients with compromised immune systems."}
{"id": "PMID:208497", "title": "Acute viral hepatitis.", "content": "It is now possible to define two forms of acute viral hepatitis by means of specific serological tests and at least one other form by exclusion. These diseases are known as hepatitis A, hepatitis B and non A non B hepatitis respectively. Major features of the virology, pathogenesis, laboratory diagnosis, epidemiology, mode of spread and control of each disease are briefly reviewed.", "contents": "Acute viral hepatitis. It is now possible to define two forms of acute viral hepatitis by means of specific serological tests and at least one other form by exclusion. These diseases are known as hepatitis A, hepatitis B and non A non B hepatitis respectively. Major features of the virology, pathogenesis, laboratory diagnosis, epidemiology, mode of spread and control of each disease are briefly reviewed."}
{"id": "PMID:208498", "title": "Cytomegalovirus and herpes simplex virus: wolves in sheep's clothing.", "content": "The herpesviruses cytomegalovirus and herpes simplex are common human infections. They are usually subclinical, but can cause significant or even fatal disease. The foetus, the newborn and the immunocompromised are particularly vulnerable to the serious consequences of these opportunistic infections.", "contents": "Cytomegalovirus and herpes simplex virus: wolves in sheep's clothing. The herpesviruses cytomegalovirus and herpes simplex are common human infections. They are usually subclinical, but can cause significant or even fatal disease. The foetus, the newborn and the immunocompromised are particularly vulnerable to the serious consequences of these opportunistic infections."}
{"id": "PMID:208499", "title": "A test for foetal gene expression at the level of transcription in hepatoms.", "content": "The presence of a variety of embryonic and foetal gene products in neoplasms is well documented. Two such products, i.e. carcinoembryonic antigen and alpha foetoprotein, are currently being used for clinical diagnosis and the assessment of prognosis. The purpose of this study has been to examine the possibility of the reactivation of a foetal gene associated with foetal liver in the Morris 5123C hepatoma and host liver after prolonged tumour bearing. The foetal gene for globin was chosen for study as production of foetal globin in cancer patients has been observed and the technique for quantiation of globin messenger RNA is available. The quantitation of globin mRNA permits the identification of a gene product which is not related to the tissue of origin of the tumor being studied and which is influenced by pre-translational control mechanisms only. The influence of tumour bearing on foetal globin gene expression by the host liver is also reported. We report molecular hybridization studies of total nucleic acid extracts from foetal, 2-day neonatal, adult and host liver and the Morris 5123C transplantable hepatoma with a complementary DNA copy of globin messenger RNA. The results indicate that there is no activation of the foetal globin gene in these tissues in spite of erythrocytosis in the host animal.", "contents": "A test for foetal gene expression at the level of transcription in hepatoms. The presence of a variety of embryonic and foetal gene products in neoplasms is well documented. Two such products, i.e. carcinoembryonic antigen and alpha foetoprotein, are currently being used for clinical diagnosis and the assessment of prognosis. The purpose of this study has been to examine the possibility of the reactivation of a foetal gene associated with foetal liver in the Morris 5123C hepatoma and host liver after prolonged tumour bearing. The foetal gene for globin was chosen for study as production of foetal globin in cancer patients has been observed and the technique for quantiation of globin messenger RNA is available. The quantitation of globin mRNA permits the identification of a gene product which is not related to the tissue of origin of the tumor being studied and which is influenced by pre-translational control mechanisms only. The influence of tumour bearing on foetal globin gene expression by the host liver is also reported. We report molecular hybridization studies of total nucleic acid extracts from foetal, 2-day neonatal, adult and host liver and the Morris 5123C transplantable hepatoma with a complementary DNA copy of globin messenger RNA. The results indicate that there is no activation of the foetal globin gene in these tissues in spite of erythrocytosis in the host animal."}
{"id": "PMID:208505", "title": "Electron-paramagnetic-resonance studies of the mechanism of leaf nitrite reductase. Signals from the iron-sulphur centre and haem under turnover conditions.", "content": "Low-temperature e.p.r. spectra are presented of nitrite reductase purified from leaves of vegetable marrow (Cucurbita pepo). The oxidized enzyme showed a spectrum at g=6.86, 4.98 and 1.95 corresponding to high-spin Fe(3+) in sirohaem, which disappeared slowly on treatment with nitrite. The midpoint potential of the sirohaem was estimated to be -120mV. On reduction with Na(2)S(2)O(4) or Na(2)S(2)O(4)+Methyl Viologen a spectrum at g=2.038, 1.944 and 1.922 was observed, due to a reduced iron-sulphur centre. The midpoint potential of this centre was very low, about -570mV at pH8.1, decreasing with increasing pH. On addition of cyanide, which binds to haem, and Na(2)S(2)O(4), the iron-sulphur centre became further reduced. We think that this is due to an increased midpoint potential of the iron-sulphur centre. Other ligands to haem, such as CO and the reaction product NH(3), had similar but less pronounced effects, and also changed the lineshape of the iron-sulphur signal. Samples were prepared of the enzyme frozen during the reaction with nitrite, Methyl Viologen and Na(2)S(2)O(4) in various proportions. Signals were interpreted as due to the reduced iron-sulphur centre (with slightly different g values), a haem-NO complex and reduced Methyl Viologen. In the presence of an excess of nitrite, the haem-NO spectrum was more intense, whereas in the presence of an excess of Na(2)S(2)O(4) it was weaker, and disappeared at the end of the reaction. A reaction sequence is proposed for the enzyme, in which the haem-NO complex is an intermediate, followed by other e.p.r.-silent states, leading to the production of NH(4) (+).", "contents": "Electron-paramagnetic-resonance studies of the mechanism of leaf nitrite reductase. Signals from the iron-sulphur centre and haem under turnover conditions. Low-temperature e.p.r. spectra are presented of nitrite reductase purified from leaves of vegetable marrow (Cucurbita pepo). The oxidized enzyme showed a spectrum at g=6.86, 4.98 and 1.95 corresponding to high-spin Fe(3+) in sirohaem, which disappeared slowly on treatment with nitrite. The midpoint potential of the sirohaem was estimated to be -120mV. On reduction with Na(2)S(2)O(4) or Na(2)S(2)O(4)+Methyl Viologen a spectrum at g=2.038, 1.944 and 1.922 was observed, due to a reduced iron-sulphur centre. The midpoint potential of this centre was very low, about -570mV at pH8.1, decreasing with increasing pH. On addition of cyanide, which binds to haem, and Na(2)S(2)O(4), the iron-sulphur centre became further reduced. We think that this is due to an increased midpoint potential of the iron-sulphur centre. Other ligands to haem, such as CO and the reaction product NH(3), had similar but less pronounced effects, and also changed the lineshape of the iron-sulphur signal. Samples were prepared of the enzyme frozen during the reaction with nitrite, Methyl Viologen and Na(2)S(2)O(4) in various proportions. Signals were interpreted as due to the reduced iron-sulphur centre (with slightly different g values), a haem-NO complex and reduced Methyl Viologen. In the presence of an excess of nitrite, the haem-NO spectrum was more intense, whereas in the presence of an excess of Na(2)S(2)O(4) it was weaker, and disappeared at the end of the reaction. A reaction sequence is proposed for the enzyme, in which the haem-NO complex is an intermediate, followed by other e.p.r.-silent states, leading to the production of NH(4) (+)."}
{"id": "PMID:208506", "title": "Steady-state and pre-steady kinetic studies on mitochondrial sheep liver aldehyde dehydrogenase. A comparison with the cytoplasmic enzyme.", "content": "Kinetic studies were carried out on mitochondrial aldehyde dehydrogenase (EC 1.2.1.3) isolated from sheep liver. Steady-state studies over a wide range of acetaldehyde concentrations gave a non-linear double-reciprocal plot. The dissociation of NADH from the enzyme was a biphasic process with decay constants 0.6s-1 and 0.09s-1. Pre-steady-state kinetic data with propionaldehyde as substrate could be fitted by using the same burst rate constant (12 +/- 3s-1) over a wide range of propionaldehyde concentrations. The quenching of protein fluorescence on the binding of NAD+ to the enzyme was used to estimate apparent rate constants for binding (2 X 10(4) litre.mol-1.s-1) and dissociation (4s-1). The kinetic properties of the mitochondrial enzyme, compared with those reported for the cytoplasmic aldehyde dehydrogenase from sheep liver, show significant differences, which may be important in the oxidation of aldehydes in vivo.", "contents": "Steady-state and pre-steady kinetic studies on mitochondrial sheep liver aldehyde dehydrogenase. A comparison with the cytoplasmic enzyme. Kinetic studies were carried out on mitochondrial aldehyde dehydrogenase (EC 1.2.1.3) isolated from sheep liver. Steady-state studies over a wide range of acetaldehyde concentrations gave a non-linear double-reciprocal plot. The dissociation of NADH from the enzyme was a biphasic process with decay constants 0.6s-1 and 0.09s-1. Pre-steady-state kinetic data with propionaldehyde as substrate could be fitted by using the same burst rate constant (12 +/- 3s-1) over a wide range of propionaldehyde concentrations. The quenching of protein fluorescence on the binding of NAD+ to the enzyme was used to estimate apparent rate constants for binding (2 X 10(4) litre.mol-1.s-1) and dissociation (4s-1). The kinetic properties of the mitochondrial enzyme, compared with those reported for the cytoplasmic aldehyde dehydrogenase from sheep liver, show significant differences, which may be important in the oxidation of aldehydes in vivo."}
{"id": "PMID:208507", "title": "Kinetic studies on the esterase activity of cytoplasmic sheep liver aldehyde dehydrogenase.", "content": "The hydrolysis of 4-nitrophenyl acetate catalysed by cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) from sheep liver was studied by steady-state and transient kinetic techniques. NAD+ and NADH stimulated the steady-state rate of ester hydrolysis at concentrations expected on the basis of their Michaelis constants from the dehydrogenase reaction. At higher concentrations of the coenzymes, both NAD+ and NADH inhibited the reaction competitively with respect to 4-nitrophenyl acetate, with inhibition constants of 104 and 197 micron respectively. Propionaldehyde and chloral hydrate are competitive inhibitors of the esterase reaction. A burst in the production of 4-nitrophenoxide ion was observed, with a rate constant of 12 +/- 2s-1 and a burst amplitude that was 30% of that expected on the basis of the known NADH-binding site concentration. The rate-limiting step for the esterase reaction occurs after the formation of 4-nitrophenoxide ion. Arguments are presented for the existence of distinct ester- and aldehyde-binding sites.", "contents": "Kinetic studies on the esterase activity of cytoplasmic sheep liver aldehyde dehydrogenase. The hydrolysis of 4-nitrophenyl acetate catalysed by cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) from sheep liver was studied by steady-state and transient kinetic techniques. NAD+ and NADH stimulated the steady-state rate of ester hydrolysis at concentrations expected on the basis of their Michaelis constants from the dehydrogenase reaction. At higher concentrations of the coenzymes, both NAD+ and NADH inhibited the reaction competitively with respect to 4-nitrophenyl acetate, with inhibition constants of 104 and 197 micron respectively. Propionaldehyde and chloral hydrate are competitive inhibitors of the esterase reaction. A burst in the production of 4-nitrophenoxide ion was observed, with a rate constant of 12 +/- 2s-1 and a burst amplitude that was 30% of that expected on the basis of the known NADH-binding site concentration. The rate-limiting step for the esterase reaction occurs after the formation of 4-nitrophenoxide ion. Arguments are presented for the existence of distinct ester- and aldehyde-binding sites."}
{"id": "PMID:208508", "title": "Alkylation of deoxyribonucleic acid by carcinogens dimethyl sulphate, ethyl methanesulphonate, N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea. Relative reactivity of the phosphodiester site thymidylyl(3'-5')thymidine.", "content": "1. The ethyl phosphotriester of thymidylyl(3'-5')thymidine, dTp(Et)dT, was identified as a product from reaction of DNA with N-ethyl-N-nitrosourea, by procedures parallel to those reported previously for the methyl homologue produced by N-methyl-N-nitrosourea. 2. Enzymic degradation to yield alkyl phosphotriesters from DNA alkylated by these carcinogens and by dimethyl sulphate and ethyl methanesulphonate was studied quantitatively, and the relative yields of the triesters dTp(Alk)dT were determined. The relative reactivity of the phosphodiester group dTpdT to each of the four carcinogens was thus obtained, and compared with that of DNA overall, or with that of the N-7 atom of guanine in DNA. Relative reactivity of the phosphodiester group was lowest towards dimethyl sulphate, the least electrophilic of the reagents used, and was highest towards N-ethyl-N-nitrosourea, the most electrophilic reagent. 3. The nature of the alkyl group transferred also influenced reactivity of the phosphodiester site, since this site was relatively more reactive towards ethylation than would be predicted simply from the known Swain-Scott s values of the alkylating agents. It was therefore suggested that the steric accessibility of the weakly nucleophilic phosphodiester group on the outside of the DNA macromolecule favours its reaction with ethylating, as opposed to methylating, reagents. 4. Taking a value of the Swain-Scott nucleophilicity (n) of 2.5 for an average DNA nucleotide unit [Walles & Ehrenberg (1969) Acta Chem. Scand. 23, 1080-1084], a value of n of about 1 for the phosphodiester group was deduced, and this value was found to be 2-3 units less than that for the N-7 atom of guanine in DNA. 5. The reactivity of DNA overall was markedly high towards the alkylnitrosoureas, despite their relatively low s values. This was ascribed to an electrostatic factor that favoured reaction of the negatively charged polymer with alkyldiazonium cation intermediates.", "contents": "Alkylation of deoxyribonucleic acid by carcinogens dimethyl sulphate, ethyl methanesulphonate, N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea. Relative reactivity of the phosphodiester site thymidylyl(3'-5')thymidine. 1. The ethyl phosphotriester of thymidylyl(3'-5')thymidine, dTp(Et)dT, was identified as a product from reaction of DNA with N-ethyl-N-nitrosourea, by procedures parallel to those reported previously for the methyl homologue produced by N-methyl-N-nitrosourea. 2. Enzymic degradation to yield alkyl phosphotriesters from DNA alkylated by these carcinogens and by dimethyl sulphate and ethyl methanesulphonate was studied quantitatively, and the relative yields of the triesters dTp(Alk)dT were determined. The relative reactivity of the phosphodiester group dTpdT to each of the four carcinogens was thus obtained, and compared with that of DNA overall, or with that of the N-7 atom of guanine in DNA. Relative reactivity of the phosphodiester group was lowest towards dimethyl sulphate, the least electrophilic of the reagents used, and was highest towards N-ethyl-N-nitrosourea, the most electrophilic reagent. 3. The nature of the alkyl group transferred also influenced reactivity of the phosphodiester site, since this site was relatively more reactive towards ethylation than would be predicted simply from the known Swain-Scott s values of the alkylating agents. It was therefore suggested that the steric accessibility of the weakly nucleophilic phosphodiester group on the outside of the DNA macromolecule favours its reaction with ethylating, as opposed to methylating, reagents. 4. Taking a value of the Swain-Scott nucleophilicity (n) of 2.5 for an average DNA nucleotide unit [Walles & Ehrenberg (1969) Acta Chem. Scand. 23, 1080-1084], a value of n of about 1 for the phosphodiester group was deduced, and this value was found to be 2-3 units less than that for the N-7 atom of guanine in DNA. 5. The reactivity of DNA overall was markedly high towards the alkylnitrosoureas, despite their relatively low s values. This was ascribed to an electrostatic factor that favoured reaction of the negatively charged polymer with alkyldiazonium cation intermediates."}
{"id": "PMID:208509", "title": "Inhibition by ethanol, acetaldehyde and trifluoroethanol of reactions catalysed by yeast and horse liver alcohol dehydrogenases.", "content": "1. Produced inhibition by ethanol of the acetaldehyde-NADH reaction, catalysed by the alcohol dehydrogenases from yeast and horse liver, was studied at 25 degrees C and pH 6-9. 2. The results with yeast alcohol dehydrogenase are generally consistent with the preferred-pathway mechanism proposed previously [Dickenson & Dickinson (1975) Biochem. J. 147, 303-311]. The observed hyperbolic inhibition by ethanol of the maximum rate of acetaldehyde reduction confirms the existence of the alternative pathway involving an enzyme-ethanol complex. 3. The maximum rate of acetaldehyde reduction with horse liver alcohol dehydrogenase is also subject to hyperbolic inhibition by ethanol. 4. The measured inhibition constants for ethanol provide some of the information required in the determination of the dissociation constant for ethanol from the active ternary complex. 5. Product inhibition by acetaldehyde of the ethanol-NAD+ reaction with yeast alcohol dehydrogenase was examined briefly. The results are consistent with the proposed mechanism. However, the nature of the inhibition of the maximum rate cannot be determined within the accessible range of experimental conditions. 6. Inhibition of yeast alcohol dehydrogenase by trifluoroethanol was studied at 25 degrees C and pH 6-10. The inhibition was competitive with respect to ethanol in the ethanol-NAD+ reaction. Estimates were made of the dissociation constant for trifluoroethanol from the enzyme-NAD+-trifluoroethanol complex in the range pH6-10.", "contents": "Inhibition by ethanol, acetaldehyde and trifluoroethanol of reactions catalysed by yeast and horse liver alcohol dehydrogenases. 1. Produced inhibition by ethanol of the acetaldehyde-NADH reaction, catalysed by the alcohol dehydrogenases from yeast and horse liver, was studied at 25 degrees C and pH 6-9. 2. The results with yeast alcohol dehydrogenase are generally consistent with the preferred-pathway mechanism proposed previously [Dickenson & Dickinson (1975) Biochem. J. 147, 303-311]. The observed hyperbolic inhibition by ethanol of the maximum rate of acetaldehyde reduction confirms the existence of the alternative pathway involving an enzyme-ethanol complex. 3. The maximum rate of acetaldehyde reduction with horse liver alcohol dehydrogenase is also subject to hyperbolic inhibition by ethanol. 4. The measured inhibition constants for ethanol provide some of the information required in the determination of the dissociation constant for ethanol from the active ternary complex. 5. Product inhibition by acetaldehyde of the ethanol-NAD+ reaction with yeast alcohol dehydrogenase was examined briefly. The results are consistent with the proposed mechanism. However, the nature of the inhibition of the maximum rate cannot be determined within the accessible range of experimental conditions. 6. Inhibition of yeast alcohol dehydrogenase by trifluoroethanol was studied at 25 degrees C and pH 6-10. The inhibition was competitive with respect to ethanol in the ethanol-NAD+ reaction. Estimates were made of the dissociation constant for trifluoroethanol from the enzyme-NAD+-trifluoroethanol complex in the range pH6-10."}
{"id": "PMID:208510", "title": "Estimation of rate and dissociation constants involving ternary complexes in reactions catalysed by yeast alcohol dehydrogenase.", "content": "Stopped-flow studies of oxidation of butan-1-ol and propan-2-ol by NAD(+) in the presence of Phenol Red and large concentrations of yeast alcohol dehydrogenase give no evidence for the participation of a group of pK(a) approx. 7.6 in alcohol binding. Such a group has been implicated in ethanol binding to horse liver alcohol dehydrogenase [Shore, Gutfreund, Brooks, Santiago & Santiago (1974) Biochemistry13, 4185-4190]. The present result supports previous findings based on steady-state kinetic studies with the yeast enzyme. Stopped-flow studies of the yeast alcohol dehydrogenase-catalysed reduction of acetaldehyde by NADH in the presence of ethanol as product inhibitor indicate that the rate-limiting step is NAD(+) release from the enzyme-NAD(+)-ethanol product complex. This finding permits calculation of K(3), the dissociation constant for ethanol from the enzyme-NAD(+)-ethanol complex, by using the product-inhibition data of Dickenson & Dickinson (1978) (Biochem. J.171, 613-627). The calculations show that K(3) varies very little with pH in the range 5.95-8.9, and this agrees with the findings of the stopped-flow experiments described above. Absorption and fluorescence measurements on mixtures of substrates and coenzymes in the presence of high concentrations of alcohol dehydrogenase have been used to estimate values for the ratio [enzyme-NADH-acetaldehyde]/ [enzyme-NAD(+)-ethanol] at equilibrium. The values obtained were in the range 0.11+/-0.04, and this value together with estimates of K(3) was used to provide estimates of values for rate constants and dissociation constants for steps within the catalytic mechanism.", "contents": "Estimation of rate and dissociation constants involving ternary complexes in reactions catalysed by yeast alcohol dehydrogenase. Stopped-flow studies of oxidation of butan-1-ol and propan-2-ol by NAD(+) in the presence of Phenol Red and large concentrations of yeast alcohol dehydrogenase give no evidence for the participation of a group of pK(a) approx. 7.6 in alcohol binding. Such a group has been implicated in ethanol binding to horse liver alcohol dehydrogenase [Shore, Gutfreund, Brooks, Santiago & Santiago (1974) Biochemistry13, 4185-4190]. The present result supports previous findings based on steady-state kinetic studies with the yeast enzyme. Stopped-flow studies of the yeast alcohol dehydrogenase-catalysed reduction of acetaldehyde by NADH in the presence of ethanol as product inhibitor indicate that the rate-limiting step is NAD(+) release from the enzyme-NAD(+)-ethanol product complex. This finding permits calculation of K(3), the dissociation constant for ethanol from the enzyme-NAD(+)-ethanol complex, by using the product-inhibition data of Dickenson & Dickinson (1978) (Biochem. J.171, 613-627). The calculations show that K(3) varies very little with pH in the range 5.95-8.9, and this agrees with the findings of the stopped-flow experiments described above. Absorption and fluorescence measurements on mixtures of substrates and coenzymes in the presence of high concentrations of alcohol dehydrogenase have been used to estimate values for the ratio [enzyme-NADH-acetaldehyde]/ [enzyme-NAD(+)-ethanol] at equilibrium. The values obtained were in the range 0.11+/-0.04, and this value together with estimates of K(3) was used to provide estimates of values for rate constants and dissociation constants for steps within the catalytic mechanism."}
{"id": "PMID:208511", "title": "Electron paramagnetic resonance in biochemistry. Computer simulation of spectra from frozen aqueous samples.", "content": "Two computer programs are described; they can be used to simulate e.p.r. spectra of effective spin-1/2 systems in frozen aqueous samples. One program is written in BASIC and the other in FORTRAN IV. Both programs are deposited as a Supplementary Publication (SUP 50082; 27 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7QB, U.K. References are given to the applications of these programs in biochemical work.", "contents": "Electron paramagnetic resonance in biochemistry. Computer simulation of spectra from frozen aqueous samples. Two computer programs are described; they can be used to simulate e.p.r. spectra of effective spin-1/2 systems in frozen aqueous samples. One program is written in BASIC and the other in FORTRAN IV. Both programs are deposited as a Supplementary Publication (SUP 50082; 27 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7QB, U.K. References are given to the applications of these programs in biochemical work."}
{"id": "PMID:208512", "title": "Electron-paramagnetic-resonance spectroscopy of complexes of xanthine oxidase with xanthine and uric acid.", "content": "Molybdenum(V) e.p.r. signals from reduced functional milk xanthine oxidase molecules (the Rapid signals), obtained in the presence of purine substrates and products, were further investigated [cf. Bray & V\u00e4nng\u00e5rd, (1969) Biochem. J. 114, 725-734; Pick & Bray (1969) Biochem. J. 114, 735-742]. Xanthine forms two complexes with the enzyme that are believed to correspond to different orientations of the substrate molecule in the active site. Only one complex appears to undergo the catalytic reaction. Non-productive complexes, analogous to theone with xanthine, are not formed by 1-methylxanthine or purine. Uric acid forms more than one e.p.r.-detectable complex, one of which is analogous to the non-productive xanthine complex. The computer program used for handing the e.p.r. data is described briefly.", "contents": "Electron-paramagnetic-resonance spectroscopy of complexes of xanthine oxidase with xanthine and uric acid. Molybdenum(V) e.p.r. signals from reduced functional milk xanthine oxidase molecules (the Rapid signals), obtained in the presence of purine substrates and products, were further investigated [cf. Bray & V\u00e4nng\u00e5rd, (1969) Biochem. J. 114, 725-734; Pick & Bray (1969) Biochem. J. 114, 735-742]. Xanthine forms two complexes with the enzyme that are believed to correspond to different orientations of the substrate molecule in the active site. Only one complex appears to undergo the catalytic reaction. Non-productive complexes, analogous to theone with xanthine, are not formed by 1-methylxanthine or purine. Uric acid forms more than one e.p.r.-detectable complex, one of which is analogous to the non-productive xanthine complex. The computer program used for handing the e.p.r. data is described briefly."}
{"id": "PMID:208513", "title": "Cross-linking of erythrocyte membrane proteins by periodate and intramembrane particle distribution.", "content": "Treatment of isolated human erythrocyte membranes at pH 7.4 with 0.1-0.5 mM-sodium periodate specifically cross-linked some of the spectrin polypeptides. Treatment with 2 mM-periodate resulted in complete cross-linking of spectrin and partial cross-linking of other polypeptides. The latter treatment also caused aggregation of the intramembrane particles made visible by freeze-fracturing. When membranes that had been treated with 2 mM-periodate were depleted of spectrin by treatment with 0.1 mM-EDTA, extensive aggregation of the intramembrane particles occurred.", "contents": "Cross-linking of erythrocyte membrane proteins by periodate and intramembrane particle distribution. Treatment of isolated human erythrocyte membranes at pH 7.4 with 0.1-0.5 mM-sodium periodate specifically cross-linked some of the spectrin polypeptides. Treatment with 2 mM-periodate resulted in complete cross-linking of spectrin and partial cross-linking of other polypeptides. The latter treatment also caused aggregation of the intramembrane particles made visible by freeze-fracturing. When membranes that had been treated with 2 mM-periodate were depleted of spectrin by treatment with 0.1 mM-EDTA, extensive aggregation of the intramembrane particles occurred."}
{"id": "PMID:208514", "title": "Substrate, metal and template effects on inhibition of bacteriophage-qbeta ribonucleic acid polymerase by ortho- and pyro-phosphate.", "content": "Two reactions of bacteriophage-Qbeta RNA polymerase with synthetic templates were characterized and used to study the effects of substrate, metal and template on inhibition by Pi and PPi. Analysis of the poly(C)-dependent reaction yielded results on kinetics, GTP-dependence, preference for Mn2+ over Mg2+, and Michaelis constants for template similar to those in the literature. New data are provided for the poly(U2,C)-dependent reaction. Our results suggest that GTP and Mn2+ can form relatively stable complexes with the polymerase and that such complexes change the interaction of the enzyme with the inhibitors, Pi and PPi.", "contents": "Substrate, metal and template effects on inhibition of bacteriophage-qbeta ribonucleic acid polymerase by ortho- and pyro-phosphate. Two reactions of bacteriophage-Qbeta RNA polymerase with synthetic templates were characterized and used to study the effects of substrate, metal and template on inhibition by Pi and PPi. Analysis of the poly(C)-dependent reaction yielded results on kinetics, GTP-dependence, preference for Mn2+ over Mg2+, and Michaelis constants for template similar to those in the literature. New data are provided for the poly(U2,C)-dependent reaction. Our results suggest that GTP and Mn2+ can form relatively stable complexes with the polymerase and that such complexes change the interaction of the enzyme with the inhibitors, Pi and PPi."}
{"id": "PMID:208515", "title": "Partial purification and properties of branched-chain 2-oxo acid dehydrogenase of ox liver.", "content": "1. A branched-chain 2-oxo acid dehydrogenase was partially purified from ox liver mitochondria. 2. The preparation oxidized 4-methyl-2-oxopentanoate, 3-methyl-2-oxobutyrate and D- and L-3-methyl-2-oxopentanoate. The apparent Km values for the oxo acids and for thiamin pyrophosphate, CoA, NAD+ and Mg2+ were determined. 3. The oxidation of each oxo acid was inhibited by isovaleryl (3-methylbutyryl)-CoA (competitive with CoA) and by NADH (competitive with NAD+); Ki values were determined. 4. The preparation showed substrate inhibition with each 2-oxo acid. The oxidative decarboxylation of 4-methyl-2-oxo[1-14C]pentanoate was inhibited by 3-methyl-2-oxobutyrate and DL-3-methyl-2-oxopentanoate, but not by pyruvate. The Vmax. with 3-methyl-2-oxobutyrate as variable substrate was not increased by the presence of each of the other 2-oxo acids. 5. Ox heart pyruvate dehydrogenase did not oxidize these branched-chain 2-oxo acids and it was not inhibited by isovaleryl-CoA. The branched-chain 2-oxo acid dehydrogenase activity (unlike that of pyruvate dehydrogenase) was not inhibited by acetyl-CoA. 6. It is concluded that the branched-chain 2-oxo acid dehydrogenase activity is distinct from that of pyruvate dehydrogenase, and that a single complex may oxidize all three branched-chain 2-oxo acids.", "contents": "Partial purification and properties of branched-chain 2-oxo acid dehydrogenase of ox liver. 1. A branched-chain 2-oxo acid dehydrogenase was partially purified from ox liver mitochondria. 2. The preparation oxidized 4-methyl-2-oxopentanoate, 3-methyl-2-oxobutyrate and D- and L-3-methyl-2-oxopentanoate. The apparent Km values for the oxo acids and for thiamin pyrophosphate, CoA, NAD+ and Mg2+ were determined. 3. The oxidation of each oxo acid was inhibited by isovaleryl (3-methylbutyryl)-CoA (competitive with CoA) and by NADH (competitive with NAD+); Ki values were determined. 4. The preparation showed substrate inhibition with each 2-oxo acid. The oxidative decarboxylation of 4-methyl-2-oxo[1-14C]pentanoate was inhibited by 3-methyl-2-oxobutyrate and DL-3-methyl-2-oxopentanoate, but not by pyruvate. The Vmax. with 3-methyl-2-oxobutyrate as variable substrate was not increased by the presence of each of the other 2-oxo acids. 5. Ox heart pyruvate dehydrogenase did not oxidize these branched-chain 2-oxo acids and it was not inhibited by isovaleryl-CoA. The branched-chain 2-oxo acid dehydrogenase activity (unlike that of pyruvate dehydrogenase) was not inhibited by acetyl-CoA. 6. It is concluded that the branched-chain 2-oxo acid dehydrogenase activity is distinct from that of pyruvate dehydrogenase, and that a single complex may oxidize all three branched-chain 2-oxo acids."}
{"id": "PMID:208516", "title": "Low-temperature kinetics of the reaction of oxygen and solubilized cytochrome oxidase.", "content": "The reaction of solubilized cytochrome oxidase in the fully reduced state with O2 at low temperatures reveals components with characteristics similar to those observed with the membrane-bound oxidase, namely compounds A and B, which are proposed to be 'oxy' and 'peroxy' compounds respectively. Similar species are identified in both solubilized and membrane-bound oxidases; the reaction velocity constant for the reation with O2 and the dissociation constant are decreased 2-3-fold in the solubilied preparation as compared with the membrane-bound species, owing to decreased reactivity towards O2 in the former. The oxidase prepared in the mixed-valence state shows the distinctive absorption band characteristic of compound C, identified in the membrane-bound oxidase. The assignment of the alpha, beta, gamma and near-i.r. absorption bands to possible valence states of these compounds is made.", "contents": "Low-temperature kinetics of the reaction of oxygen and solubilized cytochrome oxidase. The reaction of solubilized cytochrome oxidase in the fully reduced state with O2 at low temperatures reveals components with characteristics similar to those observed with the membrane-bound oxidase, namely compounds A and B, which are proposed to be 'oxy' and 'peroxy' compounds respectively. Similar species are identified in both solubilized and membrane-bound oxidases; the reaction velocity constant for the reation with O2 and the dissociation constant are decreased 2-3-fold in the solubilied preparation as compared with the membrane-bound species, owing to decreased reactivity towards O2 in the former. The oxidase prepared in the mixed-valence state shows the distinctive absorption band characteristic of compound C, identified in the membrane-bound oxidase. The assignment of the alpha, beta, gamma and near-i.r. absorption bands to possible valence states of these compounds is made."}
{"id": "PMID:208517", "title": "Thyrotropin-stimulated recruitment of free monoribosomes on to membrane-bound thyroglobulin-synthesizing polyribosomes.", "content": "Treatment of ox and dog thyroid slices in vitro with either thyrotropin or dibutyryl cyclic AMP elicited a variety of changes in polyribosome distribution. The most marked and consistent responses were decreases in both free and membrane-bound monoribosomes with a concomitant increase in the specific peak of thyroglobulin-synthesizing polyribosomes. On some occasions there was a shift towards heavier aggregates in the free polyribosomes. The increase in the amount of thyroglobulin-synthesizing polyribosomes was not accompanied by a shift in its location on the gradients. These changes were apparent within 30 min of thyrotropin addition and within 60 min of the addition of dibutyryl cyclic AMP. It is suggested that the major initial effect on translation of both thyrotropin and dibutyryl cyclic AMP is to stimulate the recruitment of pre-existing free monoribosomes on to pre-existing unloaded or under-loaded thyroglobulin mRNA molecules.", "contents": "Thyrotropin-stimulated recruitment of free monoribosomes on to membrane-bound thyroglobulin-synthesizing polyribosomes. Treatment of ox and dog thyroid slices in vitro with either thyrotropin or dibutyryl cyclic AMP elicited a variety of changes in polyribosome distribution. The most marked and consistent responses were decreases in both free and membrane-bound monoribosomes with a concomitant increase in the specific peak of thyroglobulin-synthesizing polyribosomes. On some occasions there was a shift towards heavier aggregates in the free polyribosomes. The increase in the amount of thyroglobulin-synthesizing polyribosomes was not accompanied by a shift in its location on the gradients. These changes were apparent within 30 min of thyrotropin addition and within 60 min of the addition of dibutyryl cyclic AMP. It is suggested that the major initial effect on translation of both thyrotropin and dibutyryl cyclic AMP is to stimulate the recruitment of pre-existing free monoribosomes on to pre-existing unloaded or under-loaded thyroglobulin mRNA molecules."}
{"id": "PMID:208518", "title": "The simultaneous release by bone explants in culture and the parallel activation of procollagenase and of a latent neutral proteinase that degrades cartilage proteoglycans and denatured collagen.", "content": "1. A latent neutral proteinase was found in culture media of mouse bone explants. Its accumulation during the cultures is closely parallel to that of procollagenase; both require the presence of heparin in the media. 2. Latent neutral proteinase was activated by several treatments of the media known to activate procollagenase, such as limited proteolysis by trypsin, chymotrypsin, plasmin or kallikrein, dialysis against 3 M-NaSCN at 4 degrees C and prolonged preincubation at 25 degrees C. Its activation often followed that of the procollagenase present in the same media. 3. Activation of neutral proteinase (as does that of procollagenase) by trypsin or plasmin involved two successive steps: the activation of a latent endogenous activator present in the media followed by the activation of neutral proteinase itself by that activator. 4. The proteinase degrades cartilage proteoglycans, denatured collagen (Azocoll) and casein at neutral pH; it is inhibited by EDTA, cysteine or serum. Collagenase is not inhibited by casein or Azocoll and is less resistant to heat or to trypsin than is the proteinase. Partial separation of the two enzymes was achieved by gel filtration of the media but not by fractional (NH4)2SO4 precipitation, by ion exchange or by affinity chromatography on Sepharose-collagen. These fractionations did not activate latent enzymes. 5. Trypsin activation decreases the molecular weight of both latent enzymes (60 000-70 000) by 20 000-30 000, as determined by gel filtration of media after removal of heparin. 6. The latency of both enzymes could be due either to a zymogen or to an enzyme-inhibitor complex. A thermostable inhibitor of both enzymes was found in some media. However, combinations of either enzyme with that inhibitor were not reactivated by trypsin, indicating that this inhibitor is unlikely to be the cause of the latency.", "contents": "The simultaneous release by bone explants in culture and the parallel activation of procollagenase and of a latent neutral proteinase that degrades cartilage proteoglycans and denatured collagen. 1. A latent neutral proteinase was found in culture media of mouse bone explants. Its accumulation during the cultures is closely parallel to that of procollagenase; both require the presence of heparin in the media. 2. Latent neutral proteinase was activated by several treatments of the media known to activate procollagenase, such as limited proteolysis by trypsin, chymotrypsin, plasmin or kallikrein, dialysis against 3 M-NaSCN at 4 degrees C and prolonged preincubation at 25 degrees C. Its activation often followed that of the procollagenase present in the same media. 3. Activation of neutral proteinase (as does that of procollagenase) by trypsin or plasmin involved two successive steps: the activation of a latent endogenous activator present in the media followed by the activation of neutral proteinase itself by that activator. 4. The proteinase degrades cartilage proteoglycans, denatured collagen (Azocoll) and casein at neutral pH; it is inhibited by EDTA, cysteine or serum. Collagenase is not inhibited by casein or Azocoll and is less resistant to heat or to trypsin than is the proteinase. Partial separation of the two enzymes was achieved by gel filtration of the media but not by fractional (NH4)2SO4 precipitation, by ion exchange or by affinity chromatography on Sepharose-collagen. These fractionations did not activate latent enzymes. 5. Trypsin activation decreases the molecular weight of both latent enzymes (60 000-70 000) by 20 000-30 000, as determined by gel filtration of media after removal of heparin. 6. The latency of both enzymes could be due either to a zymogen or to an enzyme-inhibitor complex. A thermostable inhibitor of both enzymes was found in some media. However, combinations of either enzyme with that inhibitor were not reactivated by trypsin, indicating that this inhibitor is unlikely to be the cause of the latency."}
{"id": "PMID:208581", "title": "Xenotropic virus and autoimmunity in NZB mice.", "content": "The high-grade expression of xenotropic virus in NZB mice is determined by two autosomal dominant loci (Nzv-1 and Nzv-2). The progeny of crosses between NZB and the \"nonautoimmune\" virus-negative SWR strain segregate into three phenotypes: high-virus, low-virus, and virus-negative. The virologic phenotypes of the animals could be dissociated from the presence of either autoantibodies or immune complex-deposit nephritis and the latter could develop in the crosses without deposits of viral antigens in the glomeruli.", "contents": "Xenotropic virus and autoimmunity in NZB mice. The high-grade expression of xenotropic virus in NZB mice is determined by two autosomal dominant loci (Nzv-1 and Nzv-2). The progeny of crosses between NZB and the \"nonautoimmune\" virus-negative SWR strain segregate into three phenotypes: high-virus, low-virus, and virus-negative. The virologic phenotypes of the animals could be dissociated from the presence of either autoantibodies or immune complex-deposit nephritis and the latter could develop in the crosses without deposits of viral antigens in the glomeruli."}
{"id": "PMID:208582", "title": "Type C RNA virus expression in systemic lupus erythematosus. New Zealand mouse model and human disease.", "content": "An antigen recognized by antisera produced against p30 (core) proteins of the four chief groups of mammalian type C viruses (murine, feline, RD-114 related to endogenous primate, and infectious primate group) is located in an immune-complex pattern in some renal glomeruli of human SLE patients with lupus proliferative glomerulonephritis but is not detected in normal or pathological control human kidneys. This antigen cross-reacts with p30 interspecies determinants shared by the four chief virus groups and cross-reacts with a partially purified antigen extracted from human SLE spleen. The human SLE spleen antigen cross-reacts with p30 group antigen of RD-114 virus but not of feline or murine viruses. Some host immunoglobulins eluted from a human SLE kidney by acid-buffer show antibody-like activity against p30 group antigen of RD-114 virus but not of simian, feline, or murine viruses.", "contents": "Type C RNA virus expression in systemic lupus erythematosus. New Zealand mouse model and human disease. An antigen recognized by antisera produced against p30 (core) proteins of the four chief groups of mammalian type C viruses (murine, feline, RD-114 related to endogenous primate, and infectious primate group) is located in an immune-complex pattern in some renal glomeruli of human SLE patients with lupus proliferative glomerulonephritis but is not detected in normal or pathological control human kidneys. This antigen cross-reacts with p30 interspecies determinants shared by the four chief virus groups and cross-reacts with a partially purified antigen extracted from human SLE spleen. The human SLE spleen antigen cross-reacts with p30 group antigen of RD-114 virus but not of feline or murine viruses. Some host immunoglobulins eluted from a human SLE kidney by acid-buffer show antibody-like activity against p30 group antigen of RD-114 virus but not of simian, feline, or murine viruses."}
{"id": "PMID:208583", "title": "Type C oncornavirus studies in systemic lupus erythematosus.", "content": "The following paper critically reviews published evidence that concerns the occurence of viruses in patients with systemic lupus erythematosus.  Special emphasis is placed on the recent studies that implicate type C oncornaviruses.  Evidence from our laboratory regarding the occurence of type C viruses in these patients is predominantly negative.  It is concluded that the pathogenesis of systemic lupus erythematosus is almost certainly multifactorial and that the part that viruses play remains hypothetical.", "contents": "Type C oncornavirus studies in systemic lupus erythematosus. The following paper critically reviews published evidence that concerns the occurence of viruses in patients with systemic lupus erythematosus.  Special emphasis is placed on the recent studies that implicate type C oncornaviruses.  Evidence from our laboratory regarding the occurence of type C viruses in these patients is predominantly negative.  It is concluded that the pathogenesis of systemic lupus erythematosus is almost certainly multifactorial and that the part that viruses play remains hypothetical."}
{"id": "PMID:208584", "title": "Regulation of cholesterol synthesis in the hyperlipoproteinaemias. Polymorphonuclear leucocyte abnormality specific to familial type II hypercholesterolaemia.", "content": "A simple procedure has been devised to give virtually pure preparations of polymorphonuclear leucocytes. This has permitted study of the regulation of cholesterol biosynthesis at cell level. Freshly isolated cells from donors with various forms of hyperlipoproteinaemia have been shown to have very low levels of cholesterol synthesis, presumably due to high circulating levels of apoprotein-B in donor plasma [1]. The activity of the rate-limiting enzyme for cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, rapidly increases as the cells are incubated in lipoprotein-deficient medium, until, by 12 h, cells from patients heterozygous for familial type IIa hypercholesterolaemia are clearly distinguished from other hyperlipoproteinaemias. The possible significance of this finding is discussed in relation to the causation and treatment of atherosclerotic disease.", "contents": "Regulation of cholesterol synthesis in the hyperlipoproteinaemias. Polymorphonuclear leucocyte abnormality specific to familial type II hypercholesterolaemia. A simple procedure has been devised to give virtually pure preparations of polymorphonuclear leucocytes. This has permitted study of the regulation of cholesterol biosynthesis at cell level. Freshly isolated cells from donors with various forms of hyperlipoproteinaemia have been shown to have very low levels of cholesterol synthesis, presumably due to high circulating levels of apoprotein-B in donor plasma [1]. The activity of the rate-limiting enzyme for cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, rapidly increases as the cells are incubated in lipoprotein-deficient medium, until, by 12 h, cells from patients heterozygous for familial type IIa hypercholesterolaemia are clearly distinguished from other hyperlipoproteinaemias. The possible significance of this finding is discussed in relation to the causation and treatment of atherosclerotic disease."}
{"id": "PMID:208586", "title": "Combined effects of clofibrate and diosgenin on cholesterol metabolism in rats.", "content": "Groups of male rats were fed various doses of clofibrate and diosgenin, both alone and in combination for 1 week. Clofibrate suppressed the diosgenin-induced increase in hepatic cholesterol synthesis but did not alter the effectiveness of diosgenin in reducing cholesterol absorption. Diosgenin did not affect the bioavailability of CPIB. Clofibrate reduced the diosgenin induced increase in biliary levels of cholesterol; none of the regimens altered biliary bile acids. The combination produced greater decreases in LDL cholesterol than did either compound alone; the diosgenin-induced elevation in HDL cholesterol was partially reversed by clofibrate. The data provide a basis for the combined use of clofibrate and diosgenin in the control of hyperlipoproteinemia.", "contents": "Combined effects of clofibrate and diosgenin on cholesterol metabolism in rats. Groups of male rats were fed various doses of clofibrate and diosgenin, both alone and in combination for 1 week. Clofibrate suppressed the diosgenin-induced increase in hepatic cholesterol synthesis but did not alter the effectiveness of diosgenin in reducing cholesterol absorption. Diosgenin did not affect the bioavailability of CPIB. Clofibrate reduced the diosgenin induced increase in biliary levels of cholesterol; none of the regimens altered biliary bile acids. The combination produced greater decreases in LDL cholesterol than did either compound alone; the diosgenin-induced elevation in HDL cholesterol was partially reversed by clofibrate. The data provide a basis for the combined use of clofibrate and diosgenin in the control of hyperlipoproteinemia."}
{"id": "PMID:208587", "title": "Lipid and lipoprotein secretion following portacaval shunt in swine.", "content": "Lipid and lipoprotein secretion were studied over 24 h in normal and portacaval shunted (PCS) fasting miniature swine after an infusion of Triton WR-1339 and [3H]amino acid mixture. The plasma triglyceride secretion rate and the secretion of triglyceride, total cholesterol and protein in the very low density lipoprotein fraction (VLDL) were linear for about 9 h after Triton. No net catabolism of the VLDL appeared to take place over the 24 h. Due to large variation, differences in the absolute secretion rates of plasma triglyceride and of the VLDL constituents could not be shown. However, the secretion of VLDL cholesterol in the PCS group appeared to be lower than that of the sham group when corrected for metabolic body size and plasma volume.", "contents": "Lipid and lipoprotein secretion following portacaval shunt in swine. Lipid and lipoprotein secretion were studied over 24 h in normal and portacaval shunted (PCS) fasting miniature swine after an infusion of Triton WR-1339 and [3H]amino acid mixture. The plasma triglyceride secretion rate and the secretion of triglyceride, total cholesterol and protein in the very low density lipoprotein fraction (VLDL) were linear for about 9 h after Triton. No net catabolism of the VLDL appeared to take place over the 24 h. Due to large variation, differences in the absolute secretion rates of plasma triglyceride and of the VLDL constituents could not be shown. However, the secretion of VLDL cholesterol in the PCS group appeared to be lower than that of the sham group when corrected for metabolic body size and plasma volume."}
{"id": "PMID:208588", "title": "High density lipoprotein catabolism before and after partial hepatectomy.", "content": "The serum decay and tissue distribution of iodine-labeled high density lipoprotein (HDL)-apoproteins were measured in rats 2--8 h after partial hepatectomy or sham-operation. A method was developed allowing continuous bloodsampling without using anticoagulantia or anaesthetics. The serum decay of HDL-apoproteins was biexponential. Neither the initial rapid phase (t 1/2 0.3 +/- 0.1 h), nor the slow phase (t 1/2 6.2 +/- 0.3 h) were influenced by the removal of 2/3 of the liver and consequently there was no effect on the fractional catabolic rate (F.C.R.: 2.9 +/- 0.2/day). The level of circulating HDL was decreased by partial hepatectomy but the chemical composition of HDL was unchanged. Total tissue HDL radioactivity in the control rats was 5.7, 2.8, 2.7, 1.0, 0.7, 0.2, 0.4 and 0.1% of the injected dose for skeletal muscle, adipose tissue, liver, jejunum, kidneys, spleen, lungs and heart, respectively. Only the value for liver was affected significantly by partial hepatectomy (0.6%). It is concluded that the in vivo degradation rate of HDL-apoproteins is not influenced by the removal of 2/3 of the liver and that the decrease in serum HDL concentration is due to an impaired rate of hepatic synthesis. These results indicate the possiblity of extrahepatic HDL-apoprotein catabolism or a stimulation of HDL-apoprotein degradation, induced by partial hepatectomy, in the remaining liver lobes.", "contents": "High density lipoprotein catabolism before and after partial hepatectomy. The serum decay and tissue distribution of iodine-labeled high density lipoprotein (HDL)-apoproteins were measured in rats 2--8 h after partial hepatectomy or sham-operation. A method was developed allowing continuous bloodsampling without using anticoagulantia or anaesthetics. The serum decay of HDL-apoproteins was biexponential. Neither the initial rapid phase (t 1/2 0.3 +/- 0.1 h), nor the slow phase (t 1/2 6.2 +/- 0.3 h) were influenced by the removal of 2/3 of the liver and consequently there was no effect on the fractional catabolic rate (F.C.R.: 2.9 +/- 0.2/day). The level of circulating HDL was decreased by partial hepatectomy but the chemical composition of HDL was unchanged. Total tissue HDL radioactivity in the control rats was 5.7, 2.8, 2.7, 1.0, 0.7, 0.2, 0.4 and 0.1% of the injected dose for skeletal muscle, adipose tissue, liver, jejunum, kidneys, spleen, lungs and heart, respectively. Only the value for liver was affected significantly by partial hepatectomy (0.6%). It is concluded that the in vivo degradation rate of HDL-apoproteins is not influenced by the removal of 2/3 of the liver and that the decrease in serum HDL concentration is due to an impaired rate of hepatic synthesis. These results indicate the possiblity of extrahepatic HDL-apoprotein catabolism or a stimulation of HDL-apoprotein degradation, induced by partial hepatectomy, in the remaining liver lobes."}
{"id": "PMID:208590", "title": "Relation of plasma high-density lipoprotein cholesterol to lipoprotein-lipase activity in adipose tissue and skeletal muscle of man.", "content": "Lipoprotein-lipase activity (LPL) was measured in biopsies of adipose tissue and skeletal muscle of normal human subjects, and the results were related to concentrations of cholesterol and triglycerides in plasma lipoproteins. Adipose-tissue LPL activity was significantly higher in females than in males, whereas no sex difference was observed in skeletal-muscle LPL activity. A highly significant positive correlation was present between the plasma high density lipoprotein (HDL) cholesterol level and LPL activity in adipose tissue (r = +0.66, P less than 0.001) but not between HDL and skeletal-muscle LPL. The results suggest that the activity of LPL in adipose tissue and the rate of catabolism of triglyceride-rich lipoproteins might be one of the factors that determine the concentration of HDL in plasma and at least partly account for the known sex difference in plasma HDL level.", "contents": "Relation of plasma high-density lipoprotein cholesterol to lipoprotein-lipase activity in adipose tissue and skeletal muscle of man. Lipoprotein-lipase activity (LPL) was measured in biopsies of adipose tissue and skeletal muscle of normal human subjects, and the results were related to concentrations of cholesterol and triglycerides in plasma lipoproteins. Adipose-tissue LPL activity was significantly higher in females than in males, whereas no sex difference was observed in skeletal-muscle LPL activity. A highly significant positive correlation was present between the plasma high density lipoprotein (HDL) cholesterol level and LPL activity in adipose tissue (r = +0.66, P less than 0.001) but not between HDL and skeletal-muscle LPL. The results suggest that the activity of LPL in adipose tissue and the rate of catabolism of triglyceride-rich lipoproteins might be one of the factors that determine the concentration of HDL in plasma and at least partly account for the known sex difference in plasma HDL level."}
{"id": "PMID:208591", "title": "Sterol balance in a patient with abetalipoproteinaemia.", "content": "Total-body cholesterol synthesis was measured in a woman with abetalipoproteinaemia and in a normal woman of similar age. The rate of synthesis of cholesterol was 15.4 +/- 4.1 mg/kg/day in the patient and 14.3 +/- 2.6 mg/kg/day in the control subject, indicating that cholesterol synthesis in the whole body is not increased in the complete absence of plasma low density lipoprotein.", "contents": "Sterol balance in a patient with abetalipoproteinaemia. Total-body cholesterol synthesis was measured in a woman with abetalipoproteinaemia and in a normal woman of similar age. The rate of synthesis of cholesterol was 15.4 +/- 4.1 mg/kg/day in the patient and 14.3 +/- 2.6 mg/kg/day in the control subject, indicating that cholesterol synthesis in the whole body is not increased in the complete absence of plasma low density lipoprotein."}
{"id": "PMID:208594", "title": "Complex sporadic colobomata.", "content": "Sporadic colobomata may be associated with a variety of secondary changes, and these have been classified and discussed with special reference to unusual findings published during recent years. Clinically some cases may appear to be neoplastic, and pathological examination may be important in demonstrating their true nature. A malformation apparently not previously reported is described.", "contents": "Complex sporadic colobomata. Sporadic colobomata may be associated with a variety of secondary changes, and these have been classified and discussed with special reference to unusual findings published during recent years. Clinically some cases may appear to be neoplastic, and pathological examination may be important in demonstrating their true nature. A malformation apparently not previously reported is described."}
{"id": "PMID:208595", "title": "Comparative feeding and nutrition in captive, non-human primates.", "content": "1. Food intake studies were carried out on three groups of captive primates (anthropoid apes (Pongidae), lemurs (Lemuridae) and marmosets (Callitrichidae). 2. Determination and analysis of the nutrient intakes were carried out by calculations based on food tables. The results from all groups were compared. 3. Marmosets were found to have higher intakes of energy and many other nutrients than the apes and lemurs. 4. The results suggest that there is a tendency towards over use of dietary supplements and foods of higher nutrient density for captive primates.", "contents": "Comparative feeding and nutrition in captive, non-human primates. 1. Food intake studies were carried out on three groups of captive primates (anthropoid apes (Pongidae), lemurs (Lemuridae) and marmosets (Callitrichidae). 2. Determination and analysis of the nutrient intakes were carried out by calculations based on food tables. The results from all groups were compared. 3. Marmosets were found to have higher intakes of energy and many other nutrients than the apes and lemurs. 4. The results suggest that there is a tendency towards over use of dietary supplements and foods of higher nutrient density for captive primates."}
{"id": "PMID:208599", "title": "Low-temperature studies of electron transfer between different cytochromes c and cytochrome c oxidase.", "content": "The ability of various native and modified cytochromes c to transfer electrons to cytochrome oxidase is compared in cytochrome c depleted beef heart mitochondrial particles. The kinetics are followed at -49 degrees C after the reaction is initiated by photolysis of the CO compound of cytochrome oxidase in the presence of oxygen. Horse, human, yeast iso-2, and carboxydinitrophenyl (CDNP)-lysine-60 horse cytochromes c all give initial rates of electron transfer that are equal to those observed in whole beef mitochondria. Euglena, CDNP-lysine-72, and CDNP-lysine-13 horse cytochromes c give rates about one-tenth that of whole mitochondria. These rates were independent of the concentration of cytochrome c. Since the inhibited cytochromes c, but not the active proteins, had previously been shown to have lowered affinity for cytochrome oxidase, the results indicate that the structural characteristics important for the association of cytochrome c and oxidase are also essential for achieving normal rates of electron transfer within the complex once formed.", "contents": "Low-temperature studies of electron transfer between different cytochromes c and cytochrome c oxidase. The ability of various native and modified cytochromes c to transfer electrons to cytochrome oxidase is compared in cytochrome c depleted beef heart mitochondrial particles. The kinetics are followed at -49 degrees C after the reaction is initiated by photolysis of the CO compound of cytochrome oxidase in the presence of oxygen. Horse, human, yeast iso-2, and carboxydinitrophenyl (CDNP)-lysine-60 horse cytochromes c all give initial rates of electron transfer that are equal to those observed in whole beef mitochondria. Euglena, CDNP-lysine-72, and CDNP-lysine-13 horse cytochromes c give rates about one-tenth that of whole mitochondria. These rates were independent of the concentration of cytochrome c. Since the inhibited cytochromes c, but not the active proteins, had previously been shown to have lowered affinity for cytochrome oxidase, the results indicate that the structural characteristics important for the association of cytochrome c and oxidase are also essential for achieving normal rates of electron transfer within the complex once formed."}
{"id": "PMID:208600", "title": "A tunnelling model to explain the reduction of ferricytochrome c by H and OH radicals.", "content": "The kinetics of the reaction of OH radicals with ferricytochrome c was studied in the time range 1 microsecond to 1 s by means of pulse radiolysis. The OH radicals reduce ferricytochrome c by 40% +/- 10%. The time course of the reduction is explained by a mechanism whereby a radical formed after hydrogen has been abstracted from the outer surface of the protein reduces the iron by electron tunnelling. We have calculated that the reducing electron in the radical is bound with an energy of at least 1.75 eV and that the frequency factor of the tunnelling process is v=10(11.5)s-1. This model accounts for the observed absorbance change in time range 5 . 10(-6)--10(-1)s. The time course of the reduction of ferricytochrome c by H radicals (Lichtin, N.N., Shafferman A. and Stein, G. (1974) Biochim. Biophys. Acta 357, 386--398) is explained by the same model.", "contents": "A tunnelling model to explain the reduction of ferricytochrome c by H and OH radicals. The kinetics of the reaction of OH radicals with ferricytochrome c was studied in the time range 1 microsecond to 1 s by means of pulse radiolysis. The OH radicals reduce ferricytochrome c by 40% +/- 10%. The time course of the reduction is explained by a mechanism whereby a radical formed after hydrogen has been abstracted from the outer surface of the protein reduces the iron by electron tunnelling. We have calculated that the reducing electron in the radical is bound with an energy of at least 1.75 eV and that the frequency factor of the tunnelling process is v=10(11.5)s-1. This model accounts for the observed absorbance change in time range 5 . 10(-6)--10(-1)s. The time course of the reduction of ferricytochrome c by H radicals (Lichtin, N.N., Shafferman A. and Stein, G. (1974) Biochim. Biophys. Acta 357, 386--398) is explained by the same model."}
{"id": "PMID:208601", "title": "Cytochrome c-cytochrome oxidase interaction at subzero temperatures.", "content": "Cytochrome oxidase forms two distinctive compounds with oxygen at --105 and --90 degrees C, one appears to be oxycytochrome oxidase (Compound A) and the other peroxycytochrome oxidase (Compound B). The functional role of compound B in the oxidation of cytochrome c has been examined in a variety of mitochondrial preparations. The rate and the extent of the reaction have been found to be dependent upon the presence of a fluid phase in the vicinity of the site of the reaction of cytochrome c and cytochrome oxidase. The kinetics of cytochrome c oxidation and of the slowly reacting component of cytochrome oxidase are found to be linked to one another even in cytochrome c depleted preparations, but under appropriate conditions, especially low temperatures, the oxidation of cytochrome c precedes that of this component of cytochrome oxidase. Based upon the identification of the slowly reacting components of cytochrome oxidase with cytochrome c, various mechanisms are considered which allow cytochrome c to be oxidized without the intervention of cytochrome a at very low temperatures, and tunneling seems an appropriate mechanism.", "contents": "Cytochrome c-cytochrome oxidase interaction at subzero temperatures. Cytochrome oxidase forms two distinctive compounds with oxygen at --105 and --90 degrees C, one appears to be oxycytochrome oxidase (Compound A) and the other peroxycytochrome oxidase (Compound B). The functional role of compound B in the oxidation of cytochrome c has been examined in a variety of mitochondrial preparations. The rate and the extent of the reaction have been found to be dependent upon the presence of a fluid phase in the vicinity of the site of the reaction of cytochrome c and cytochrome oxidase. The kinetics of cytochrome c oxidation and of the slowly reacting component of cytochrome oxidase are found to be linked to one another even in cytochrome c depleted preparations, but under appropriate conditions, especially low temperatures, the oxidation of cytochrome c precedes that of this component of cytochrome oxidase. Based upon the identification of the slowly reacting components of cytochrome oxidase with cytochrome c, various mechanisms are considered which allow cytochrome c to be oxidized without the intervention of cytochrome a at very low temperatures, and tunneling seems an appropriate mechanism."}
{"id": "PMID:208602", "title": "The effect of mitochondrial energization on cytochrome c oxidase kinetics as measured at low temperatures. I. The reaction with carbon monoxide.", "content": "The kinetics of CO binding by the cytochrome c oxidase of pigeon heart mitochondria were studied as a function of membrane energization at temperatures from 180 to 280 degrees K in an ethylene glycol/water medium. Samples energized by ATP showed acceleration of CO binding compared to those untreated or uncoupled by carbonylcyanide p-trifluoromethyoxyphenylhydrazone but only at relatively low temperatures and high CO concentrations. Experiments using samples in a \"mixed valency\" (partially oxidized) state showed that the acceleration of ligand binding is not due to the formation of a partially oxidized state via reverse electron transport. It is concluded that in the deenergized state one CO molecule can be closely associated with the cytochrome a3 heme site without actually being bound to the heme iron; in the energized state, two or more ligand molecules can occupy this intermediate position. The change in the apparent ligand capacity of a region near the heme iron in response to energization is evidence for an interaction between cytochrome oxidase and the ATPase system. Furthermore, these results suggest a control mechanism for O2 binding.", "contents": "The effect of mitochondrial energization on cytochrome c oxidase kinetics as measured at low temperatures. I. The reaction with carbon monoxide. The kinetics of CO binding by the cytochrome c oxidase of pigeon heart mitochondria were studied as a function of membrane energization at temperatures from 180 to 280 degrees K in an ethylene glycol/water medium. Samples energized by ATP showed acceleration of CO binding compared to those untreated or uncoupled by carbonylcyanide p-trifluoromethyoxyphenylhydrazone but only at relatively low temperatures and high CO concentrations. Experiments using samples in a \"mixed valency\" (partially oxidized) state showed that the acceleration of ligand binding is not due to the formation of a partially oxidized state via reverse electron transport. It is concluded that in the deenergized state one CO molecule can be closely associated with the cytochrome a3 heme site without actually being bound to the heme iron; in the energized state, two or more ligand molecules can occupy this intermediate position. The change in the apparent ligand capacity of a region near the heme iron in response to energization is evidence for an interaction between cytochrome oxidase and the ATPase system. Furthermore, these results suggest a control mechanism for O2 binding."}
{"id": "PMID:208603", "title": "The effect of mitochondrial energization on cytochrome c oxidase kinetics as measured at low temperatures. II. The binding and reduction of dioxygen.", "content": "The effect of pre-energization of isolated mitochondria by ATP at room temperature upon the kinetics of oxygen intermediates (measured at very low temperatures) of cytochrome c oxidase has been studied. It was found that \"energization\" of mitochondria at room temperature had dramatic effects on several partial reactions of cytochrome aa3. Thus, in the \"energized\" frozen state, the rate of O2 binding to ferrous cytochrome a3 and the subsequent formation of the \"peroxy\" compound B are accelerated, while oxidation of cytochromes c and c1 is inhibited. These effects of ATP are abolished by oligomycin and uncoupling agents and may, therefore, be reflections of the coupling of the mitochondrial ATP synthetase to the respiratory chain at the level of cytochrome c oxidase, which is the basis of the mechanism of coupling respiration to ATP synthesis and respiratory control.", "contents": "The effect of mitochondrial energization on cytochrome c oxidase kinetics as measured at low temperatures. II. The binding and reduction of dioxygen. The effect of pre-energization of isolated mitochondria by ATP at room temperature upon the kinetics of oxygen intermediates (measured at very low temperatures) of cytochrome c oxidase has been studied. It was found that \"energization\" of mitochondria at room temperature had dramatic effects on several partial reactions of cytochrome aa3. Thus, in the \"energized\" frozen state, the rate of O2 binding to ferrous cytochrome a3 and the subsequent formation of the \"peroxy\" compound B are accelerated, while oxidation of cytochromes c and c1 is inhibited. These effects of ATP are abolished by oligomycin and uncoupling agents and may, therefore, be reflections of the coupling of the mitochondrial ATP synthetase to the respiratory chain at the level of cytochrome c oxidase, which is the basis of the mechanism of coupling respiration to ATP synthesis and respiratory control."}
{"id": "PMID:208604", "title": "Electron spin resonance in zero magnetic field of the reaction center triplet of photosynthetic bacteria.", "content": "The decay rates kx, ky, kz of the individual spin levels of the light-induced triplet state have been accurately measured by the zero-field resonance technique under conditions of very low light intensity and a microwave sweep rate of 2.5 MHz/microseconds, which is in excess of that commonly used in optical detection magnetic resonance experiments. The rates ku found correspond well with those previously determined under somewhat different conditions (Hoff, A.J. (1976) Biochim. Biophys. Acta 440, 765--771) and with those inferred from the decay at 4.2 degrees K of the triplet-triplet absorption after picosecond excitation (Parson, W.W. and Monger, T.G. (1977) Brookhaven Symp. Biology 28, 195--212). Thus there seems no reason to doubt that PR corresponds to the triplet state detected by ESR. In a recent publication Clarke and Connors (Clarke, R.H. and Conners, R.E. (1976) Chem. Phys. Lett. 42, 69--72) published values of the rates ku which differ substantially from ours and which lead to a mean lifetime in excess of that of PR. We show that erroneous rates are obtained when the microwave sweep rate is not made fast relative to the decay of the individual spin levels. Zero-field splitting parameters for a member of photosynthetic bacteria have been measured with an accuracy of better than 0.4% for D and 1% for E. The enhanced precision as compared to conventional ESR allows one to discriminate between species of one family. Deuteration reduces the ku values by a factor of about 2, with little spin selectivity. This effect is much larger than previously observed for chlorophyll a. The present results explain the decrease in fluorescence intensity observed on microwave saturation in zero-field optical detection magnetic resonance experiments, and they also show that the simple exciton model is inadequate to derive the geometry of the reaction center dimer from the observed zerofield splitting and decay rates.", "contents": "Electron spin resonance in zero magnetic field of the reaction center triplet of photosynthetic bacteria. The decay rates kx, ky, kz of the individual spin levels of the light-induced triplet state have been accurately measured by the zero-field resonance technique under conditions of very low light intensity and a microwave sweep rate of 2.5 MHz/microseconds, which is in excess of that commonly used in optical detection magnetic resonance experiments. The rates ku found correspond well with those previously determined under somewhat different conditions (Hoff, A.J. (1976) Biochim. Biophys. Acta 440, 765--771) and with those inferred from the decay at 4.2 degrees K of the triplet-triplet absorption after picosecond excitation (Parson, W.W. and Monger, T.G. (1977) Brookhaven Symp. Biology 28, 195--212). Thus there seems no reason to doubt that PR corresponds to the triplet state detected by ESR. In a recent publication Clarke and Connors (Clarke, R.H. and Conners, R.E. (1976) Chem. Phys. Lett. 42, 69--72) published values of the rates ku which differ substantially from ours and which lead to a mean lifetime in excess of that of PR. We show that erroneous rates are obtained when the microwave sweep rate is not made fast relative to the decay of the individual spin levels. Zero-field splitting parameters for a member of photosynthetic bacteria have been measured with an accuracy of better than 0.4% for D and 1% for E. The enhanced precision as compared to conventional ESR allows one to discriminate between species of one family. Deuteration reduces the ku values by a factor of about 2, with little spin selectivity. This effect is much larger than previously observed for chlorophyll a. The present results explain the decrease in fluorescence intensity observed on microwave saturation in zero-field optical detection magnetic resonance experiments, and they also show that the simple exciton model is inadequate to derive the geometry of the reaction center dimer from the observed zerofield splitting and decay rates."}
{"id": "PMID:208605", "title": "Polymyxin binding to charged lipid membranes. An example of cooperative lipid-protein interaction.", "content": "The binding of polymyxin-B to lipid bilayer vesicles of synthetic phosphatidic acid was studied using fluorescence, ESR spectroscopy and electron microscopy. 1,6-Diphenylhexatriene (which exhibits polarized fluorescence) and pyrene decanoic acid (which forms excimers) were used as fluorescence probes to study the lipid phase transition. The polymyxin binds strongly to negatively charged lipid layers. As a result of lipid/polymyxin chain-chain interactions, the transition temperature of the lipid. This can be explained in terms of a slight expansion of the crystalline lipid lattice (Lindeman's rule). Upon addition of polymyxin to phosphatidic acid vesicles two rather sharp phase transitions (width deltaT = 5 degrees C) are observed. The upper transition (at Tu) is that of the pure lipid and the lower transition (at T1) concerns the lipid bound to the peptide. The sharpness of these transitions strongly indicates that the bilayer is characterized by a heterogeneous lateral distribution of free and bound lipid regions, one in the crystalline and the other in the fluid state. Such a domain structure was directly observed by electron microscopy (freeze etching technique). In (1 : 1) mixtures of dipalmitoyl phosphatidic acid and egg lecithin, polymyxin induces the formation of domains of charged lipid within the fluid regions of egg lecithin. With both fluorescence methods the fraction of lipid bound to polymyxin-B as a function of the peptide concentration was determined. S-shaped binding curves were obtained. The same type of binding curve is obtained for the interaction of Ca2+ with phosphatidic acid lamellae, while the binding of polylysine to such membranes is characterized by a linear or Langmuir type binding curve. The S-shaped binding curve can be explained in terms of a cooperative lipid-ligand (Ca2+, polymyxin) interaction. A model is proposed which explains the association of polymyxin within the membrane plane in terms of elastic forces caused by the elastic distortion of the (liquid crystalline) lipid layer by this highly asymmetric peptide.", "contents": "Polymyxin binding to charged lipid membranes. An example of cooperative lipid-protein interaction. The binding of polymyxin-B to lipid bilayer vesicles of synthetic phosphatidic acid was studied using fluorescence, ESR spectroscopy and electron microscopy. 1,6-Diphenylhexatriene (which exhibits polarized fluorescence) and pyrene decanoic acid (which forms excimers) were used as fluorescence probes to study the lipid phase transition. The polymyxin binds strongly to negatively charged lipid layers. As a result of lipid/polymyxin chain-chain interactions, the transition temperature of the lipid. This can be explained in terms of a slight expansion of the crystalline lipid lattice (Lindeman's rule). Upon addition of polymyxin to phosphatidic acid vesicles two rather sharp phase transitions (width deltaT = 5 degrees C) are observed. The upper transition (at Tu) is that of the pure lipid and the lower transition (at T1) concerns the lipid bound to the peptide. The sharpness of these transitions strongly indicates that the bilayer is characterized by a heterogeneous lateral distribution of free and bound lipid regions, one in the crystalline and the other in the fluid state. Such a domain structure was directly observed by electron microscopy (freeze etching technique). In (1 : 1) mixtures of dipalmitoyl phosphatidic acid and egg lecithin, polymyxin induces the formation of domains of charged lipid within the fluid regions of egg lecithin. With both fluorescence methods the fraction of lipid bound to polymyxin-B as a function of the peptide concentration was determined. S-shaped binding curves were obtained. The same type of binding curve is obtained for the interaction of Ca2+ with phosphatidic acid lamellae, while the binding of polylysine to such membranes is characterized by a linear or Langmuir type binding curve. The S-shaped binding curve can be explained in terms of a cooperative lipid-ligand (Ca2+, polymyxin) interaction. A model is proposed which explains the association of polymyxin within the membrane plane in terms of elastic forces caused by the elastic distortion of the (liquid crystalline) lipid layer by this highly asymmetric peptide."}
{"id": "PMID:208606", "title": "The effect of acclimation temperature on the activation energies of state III respiration and on the unsaturation of membrane lipids of goldfish mitochondria.", "content": "The influence of the acclimation temperature on the thermotropic behaviour of mitochondrial respiration and on the degree of unsaturation of mitochondrial membrane lipids has been studied. The mitochondria were isolated from red muscle, white muscle and liver of goldfish acclimated to 5, 20 and 30 degrees C. ADP-activated succinate oxidation was measured at different temperatures and resulted in non-linear Arrhenius-plots with breaks between 10 and 23 degrees C. As for the break-temperatures, there was found a shift downwards in preparations of decreased acclimation temperatures. This could be caused by a changed composition of membrane lipids and a simultaneous shift of the membrane phase transition temperature. Therefore, the fatty acid composition of all membrane preparations was analyzed. However, no consistent change of the degree of unsaturation due to a changed acclimation temperature could be found.", "contents": "The effect of acclimation temperature on the activation energies of state III respiration and on the unsaturation of membrane lipids of goldfish mitochondria. The influence of the acclimation temperature on the thermotropic behaviour of mitochondrial respiration and on the degree of unsaturation of mitochondrial membrane lipids has been studied. The mitochondria were isolated from red muscle, white muscle and liver of goldfish acclimated to 5, 20 and 30 degrees C. ADP-activated succinate oxidation was measured at different temperatures and resulted in non-linear Arrhenius-plots with breaks between 10 and 23 degrees C. As for the break-temperatures, there was found a shift downwards in preparations of decreased acclimation temperatures. This could be caused by a changed composition of membrane lipids and a simultaneous shift of the membrane phase transition temperature. Therefore, the fatty acid composition of all membrane preparations was analyzed. However, no consistent change of the degree of unsaturation due to a changed acclimation temperature could be found."}
{"id": "PMID:208607", "title": "Asymmetric distribution of phosphatidylethanolamine fatty acyl chains in the membrane of vesicular stomatitis virus.", "content": "The membrane of vesicular stomatitis virus (VSV) contains two distinct pools of phosphatidylethanolamine molecules which reside in the inner and outer phospholipid monolayers, respectively. 36% of the total membrane phosphatidylethanolamine is found in the outer monolayer while 64% is found in the inner. The two pools of VSV phosphatidylethanolamine can be distinguished operationally by the fact that only outer phosphatidylethanolamine is reactive in intact virions with the membrane-impermeable reagent trinitrobenzenesulfonate (TNBS). We have made use of this property to separate inner from outer VSV phosphatidylethanolamine and to determine the fatty acyl chain compositions of the two phosphatidylethanolamine pools separately. The results show that compared to outer phosphatidylethanolamine, inner phosphatidylethanolamine molecules contain a significantly higher proportion of unsaturated fatty acyl chains. Furthermore, whereas the proportion of unsaturated fatty acyl chains was found to be quite similar at the 1 and 2 glycerol carbon atoms in inner phosphatidylethanolamine, a marked dissimilarity was observed in outer phosphatidylethanolamine; outer phosphatidylethanolamine was enriched in saturated fatty acyl chains at the 1 position and in unsaturated fatty acyl chains at the 2 position. The differential fatty acyl chain composition of inner compared to outer phosphatidylethanolamine indicates that rapid, random transmembrane migration (flip-flop) of phosphatidylethanolamine does not occur in the VSV membrane. The nature of the fatty acyl chain asymmetry observed in VSV phosphatidylethanolamine does not support the view that the identity of the fatty acyl chains can uniquely specify or determine which side of the membrane individual phosphatidylethanolamine molecules come to occupy. Although fatty acyl chain asymmetry and phosphatidylethanolamine asymmetry are correlated in VSV, no simple rules can be discerned which uniquely relate the two paramaters.", "contents": "Asymmetric distribution of phosphatidylethanolamine fatty acyl chains in the membrane of vesicular stomatitis virus. The membrane of vesicular stomatitis virus (VSV) contains two distinct pools of phosphatidylethanolamine molecules which reside in the inner and outer phospholipid monolayers, respectively. 36% of the total membrane phosphatidylethanolamine is found in the outer monolayer while 64% is found in the inner. The two pools of VSV phosphatidylethanolamine can be distinguished operationally by the fact that only outer phosphatidylethanolamine is reactive in intact virions with the membrane-impermeable reagent trinitrobenzenesulfonate (TNBS). We have made use of this property to separate inner from outer VSV phosphatidylethanolamine and to determine the fatty acyl chain compositions of the two phosphatidylethanolamine pools separately. The results show that compared to outer phosphatidylethanolamine, inner phosphatidylethanolamine molecules contain a significantly higher proportion of unsaturated fatty acyl chains. Furthermore, whereas the proportion of unsaturated fatty acyl chains was found to be quite similar at the 1 and 2 glycerol carbon atoms in inner phosphatidylethanolamine, a marked dissimilarity was observed in outer phosphatidylethanolamine; outer phosphatidylethanolamine was enriched in saturated fatty acyl chains at the 1 position and in unsaturated fatty acyl chains at the 2 position. The differential fatty acyl chain composition of inner compared to outer phosphatidylethanolamine indicates that rapid, random transmembrane migration (flip-flop) of phosphatidylethanolamine does not occur in the VSV membrane. The nature of the fatty acyl chain asymmetry observed in VSV phosphatidylethanolamine does not support the view that the identity of the fatty acyl chains can uniquely specify or determine which side of the membrane individual phosphatidylethanolamine molecules come to occupy. Although fatty acyl chain asymmetry and phosphatidylethanolamine asymmetry are correlated in VSV, no simple rules can be discerned which uniquely relate the two paramaters."}
{"id": "PMID:208608", "title": "An altered response of virally transformed 3T3 cells to ouabain.", "content": "The effect of ouabain on K+ transport was examined in 3T3 and virally transformed 3T3 cells. A 10 min exposure to ouabain (10(-3) M) produced approximately 40% inhibition of the unidirectional K+ influx in all cell lines. In 3T3 cells the response was not significantly altered by up to 70 min exposure to the drug. In contrast, the continued exposure of transformed cells to ouabain produced a time-dependent increase in the K+ influx. This increased influx was shown to be accompanied by an increase in the K+ efflux. The results suggest that, in transformed cells, ouabain produces both an inhibition of Na+-K+ exchange and a stimulation of K+-K+ exchange. The latter was shown to be more readily reversible than the former.", "contents": "An altered response of virally transformed 3T3 cells to ouabain. The effect of ouabain on K+ transport was examined in 3T3 and virally transformed 3T3 cells. A 10 min exposure to ouabain (10(-3) M) produced approximately 40% inhibition of the unidirectional K+ influx in all cell lines. In 3T3 cells the response was not significantly altered by up to 70 min exposure to the drug. In contrast, the continued exposure of transformed cells to ouabain produced a time-dependent increase in the K+ influx. This increased influx was shown to be accompanied by an increase in the K+ efflux. The results suggest that, in transformed cells, ouabain produces both an inhibition of Na+-K+ exchange and a stimulation of K+-K+ exchange. The latter was shown to be more readily reversible than the former."}
{"id": "PMID:208609", "title": "Calcium-sensitive univalent cation channel formed by lysotriphosphoinositide in bilayer lipid membranes.", "content": "A calcium sensitive univalent cation channel could be formed by lysotriphosphoinositide on an artificial bilayer membrane made of oxidized cholesterol. The modified membrane was selectively permeable to univalent cations, but was only very sparingly permeable to anions or divalent cations. Selectivity sequence among group IA cations was Rb+ greater than Cs+ greater than Na+ greater than K+ greater than Li+. The conductance of the membrane was increased up to a value of about 10-2 ohm-1/cm2 with an increase in the concentration of univalent cation, and was drastically depressed by a relatively small increase in the concentration of calcium ion or other divalent cations. The sequence of depressing efficiency among divalent cations was Zn+ greater than Cd2+ greater than Ca2+ greater than Sr2+ greater than Mg2+.", "contents": "Calcium-sensitive univalent cation channel formed by lysotriphosphoinositide in bilayer lipid membranes. A calcium sensitive univalent cation channel could be formed by lysotriphosphoinositide on an artificial bilayer membrane made of oxidized cholesterol. The modified membrane was selectively permeable to univalent cations, but was only very sparingly permeable to anions or divalent cations. Selectivity sequence among group IA cations was Rb+ greater than Cs+ greater than Na+ greater than K+ greater than Li+. The conductance of the membrane was increased up to a value of about 10-2 ohm-1/cm2 with an increase in the concentration of univalent cation, and was drastically depressed by a relatively small increase in the concentration of calcium ion or other divalent cations. The sequence of depressing efficiency among divalent cations was Zn+ greater than Cd2+ greater than Ca2+ greater than Sr2+ greater than Mg2+."}
{"id": "PMID:208611", "title": "Saltatory thermal denaturation of double-stranded viral RNAs.", "content": "The double-stranded RNAs from bacteriophage phi6 and the replicative form of mengovirus denature upon heating in a series of abrupt steps which resemble the subtransitions (thermalites) observed within the high resolution profiles of small, naturally occurring DNA molecules. Such RNA thermalites are approximately an order of magnitude narrower than typical thermal subtransitions of nominally single-stranded RNA. We conclude that the same features of nucleotide sequence that give rise to cooperative denaturation in DNA genomes are to be found also in RNA genomes. Thus, high resolution thermal denaturation profiles are useful for characterizing double-stranded RNA molecules as well as native DNA in the size range of common viruses. A medium containing dimethylsulfoxide was required to lower the Tm of the RNA samples to a satisfactory temperature range. For double-stranded RNA in 50% dimethylsulfoxide, the dependence of Tm on G . C composition was greater than that of DNA in the same medium and also greater than that of double-stranded RNA in an aqueous medium. The fact that RNA thermalites are broader than DNA thermalites and that the melting temperature of double-stranded RNA has a greater dependence on base composition than that of DNA, indicates that at least one of the thermodynamic parameters for double helix formation in RNA is different from that in DNA.", "contents": "Saltatory thermal denaturation of double-stranded viral RNAs. The double-stranded RNAs from bacteriophage phi6 and the replicative form of mengovirus denature upon heating in a series of abrupt steps which resemble the subtransitions (thermalites) observed within the high resolution profiles of small, naturally occurring DNA molecules. Such RNA thermalites are approximately an order of magnitude narrower than typical thermal subtransitions of nominally single-stranded RNA. We conclude that the same features of nucleotide sequence that give rise to cooperative denaturation in DNA genomes are to be found also in RNA genomes. Thus, high resolution thermal denaturation profiles are useful for characterizing double-stranded RNA molecules as well as native DNA in the size range of common viruses. A medium containing dimethylsulfoxide was required to lower the Tm of the RNA samples to a satisfactory temperature range. For double-stranded RNA in 50% dimethylsulfoxide, the dependence of Tm on G . C composition was greater than that of DNA in the same medium and also greater than that of double-stranded RNA in an aqueous medium. The fact that RNA thermalites are broader than DNA thermalites and that the melting temperature of double-stranded RNA has a greater dependence on base composition than that of DNA, indicates that at least one of the thermodynamic parameters for double helix formation in RNA is different from that in DNA."}
{"id": "PMID:208612", "title": "Detection of Epstein-Barr virus (EBV) DNA sequences using in situ hybridization.", "content": "In situ hybridization was used to detect Epstein-Barr virus (EBV) DNA sequences under conditions where the virus DNA is replicating spontaneously and where it is induced to do so following superinfection. The in situ reaction itself is influenced by several parameters, analogous to conventional nucleic acid hybridization, consideration of which should help to optimize the designing of in situ hybridization reactions in general. Both EBV complementary RNA (cRNA) and EBV DNA synthesized in vitro can efficiently detect the virus DNA sequences in situ. The findings presented here can therefore be utilized in both the study of EBV-cell interactions and, more generally, in studies using in situ hybridization as a general approach.", "contents": "Detection of Epstein-Barr virus (EBV) DNA sequences using in situ hybridization. In situ hybridization was used to detect Epstein-Barr virus (EBV) DNA sequences under conditions where the virus DNA is replicating spontaneously and where it is induced to do so following superinfection. The in situ reaction itself is influenced by several parameters, analogous to conventional nucleic acid hybridization, consideration of which should help to optimize the designing of in situ hybridization reactions in general. Both EBV complementary RNA (cRNA) and EBV DNA synthesized in vitro can efficiently detect the virus DNA sequences in situ. The findings presented here can therefore be utilized in both the study of EBV-cell interactions and, more generally, in studies using in situ hybridization as a general approach."}
{"id": "PMID:208613", "title": "Role of silicon on diatom metabolism. IX. Differential synthesis of DNA polymerases and DNA-binding proteins during silicate starvation and recovery in Cylindrotheca fusiformis.", "content": "During recovery from silicate-starvation, a period of active DNA synthesis, synchronized cells of Cylindrotheca fusiformis incorporated 3 times more L-[U-14C]aspartate than did starved cells. Of the diatoms's four DNA polymerases, A and D are synthesized during silicate recovery, indicating that they are involved in silicate-dependent DNA replication. Polymerase B, and the chloroplast enzyme, polymerase C, are synthesized during silicate-starvation and their levels are unaffected by the addition of silicate. DEAE-Sephadex analysis of the DNA-binding proteins, labeled with [14C]- and [3H]asparate, shows that only three proteins are synthesized in cells recovering from silicate-starvation. Two of these proteins correspond to polymerases A and D, while the function of the third protein is not known. At least 15 other proteins are present in silicate-starved cells and their synthesis is repressed upon the addition of silicate. Models are proposed which describe the modes by which silicate might regulate DNA synthesis in the diatom.", "contents": "Role of silicon on diatom metabolism. IX. Differential synthesis of DNA polymerases and DNA-binding proteins during silicate starvation and recovery in Cylindrotheca fusiformis. During recovery from silicate-starvation, a period of active DNA synthesis, synchronized cells of Cylindrotheca fusiformis incorporated 3 times more L-[U-14C]aspartate than did starved cells. Of the diatoms's four DNA polymerases, A and D are synthesized during silicate recovery, indicating that they are involved in silicate-dependent DNA replication. Polymerase B, and the chloroplast enzyme, polymerase C, are synthesized during silicate-starvation and their levels are unaffected by the addition of silicate. DEAE-Sephadex analysis of the DNA-binding proteins, labeled with [14C]- and [3H]asparate, shows that only three proteins are synthesized in cells recovering from silicate-starvation. Two of these proteins correspond to polymerases A and D, while the function of the third protein is not known. At least 15 other proteins are present in silicate-starved cells and their synthesis is repressed upon the addition of silicate. Models are proposed which describe the modes by which silicate might regulate DNA synthesis in the diatom."}
{"id": "PMID:208614", "title": "Characterization and comparison of poly(adenosine dephosphoribose) synthesis and DNA synthesis in nucleotide-permeable cells.", "content": "Using eukaryotic cells that have been rendered permeable to exogenously supplied nucleotides, we have characterized the activity of the poly(adenosine diphosphoribose) (poly(ADPR)) synthesis system and compared it to the DNA synthesis complex. The synthesis of poly(ADPR) is dependent on the presence of NAD and Mg2+. It does not require ATP, NaF or a monovalent cation. It is inhibited by N-ethylmaleimide. The reaction product conforms to the nuclease susceptibilities expected for poly(ADP ribose) in that it is degraded by venom phosphodiesterase but not by DNAase of RNAase. A comparison of the effects of inhibitors of poly(ADPR) synthesis and DNA synthesis clearly distinguishes between the two enzymatic systems. Nicotinamide, 5-methyl nicotinamide, thymidine, 5-bromo deoxyuridine, adenosine diphosphoribose, caffeine and formycin all inhibit poly(ADPR) synthesis but not DNA synthesis. In contrast, araCTP, cytembena and phosphonoacetic acid all inhibit DNA synthesis but not poly(ADPR) synthesis. Addition of DNAase to the permeable cells causes a marked stimulation of poly(ADPR) synthesis. L cells in logarithmic growth were found to have high levels of activity of the DNA synthesis complex and low levels of activity of the poly(ADPR) synthesis system. In contrast, cells at plateau phase density demonstrate a decrease in the activity of the DNA synthesis complex and a marked increase in activity of the poly(ADPR) synthesis system. When examined in the presence of added DNAase, the activity of the poly(ADPR) synthesis system is the same in cells obtained from log or plateau phase cultures. This indicates that the physiologic activity of the enzyme varies while the total amount of enzyme remains constant. When the permeable cells are allowed to synthesize both poly(ADPR) and DNA simultaneously, the synthesis of one polymer has no effect on the rate of synthesis of the other.", "contents": "Characterization and comparison of poly(adenosine dephosphoribose) synthesis and DNA synthesis in nucleotide-permeable cells. Using eukaryotic cells that have been rendered permeable to exogenously supplied nucleotides, we have characterized the activity of the poly(adenosine diphosphoribose) (poly(ADPR)) synthesis system and compared it to the DNA synthesis complex. The synthesis of poly(ADPR) is dependent on the presence of NAD and Mg2+. It does not require ATP, NaF or a monovalent cation. It is inhibited by N-ethylmaleimide. The reaction product conforms to the nuclease susceptibilities expected for poly(ADP ribose) in that it is degraded by venom phosphodiesterase but not by DNAase of RNAase. A comparison of the effects of inhibitors of poly(ADPR) synthesis and DNA synthesis clearly distinguishes between the two enzymatic systems. Nicotinamide, 5-methyl nicotinamide, thymidine, 5-bromo deoxyuridine, adenosine diphosphoribose, caffeine and formycin all inhibit poly(ADPR) synthesis but not DNA synthesis. In contrast, araCTP, cytembena and phosphonoacetic acid all inhibit DNA synthesis but not poly(ADPR) synthesis. Addition of DNAase to the permeable cells causes a marked stimulation of poly(ADPR) synthesis. L cells in logarithmic growth were found to have high levels of activity of the DNA synthesis complex and low levels of activity of the poly(ADPR) synthesis system. In contrast, cells at plateau phase density demonstrate a decrease in the activity of the DNA synthesis complex and a marked increase in activity of the poly(ADPR) synthesis system. When examined in the presence of added DNAase, the activity of the poly(ADPR) synthesis system is the same in cells obtained from log or plateau phase cultures. This indicates that the physiologic activity of the enzyme varies while the total amount of enzyme remains constant. When the permeable cells are allowed to synthesize both poly(ADPR) and DNA simultaneously, the synthesis of one polymer has no effect on the rate of synthesis of the other."}
{"id": "PMID:208615", "title": "Cytoplasmic DNA synthesis in rhinovirus type 14-inoculated  KB cells.", "content": "Rhinovirus type 14 (RV14) incuced a transient statistically significant stimulation in synthesis of DNA which appeared between 0 and 3 h post-inoculation in the cytoplasm of high density monolayer cultures of KB cells. Newly synthesized DNA was measured by incorporation of [3H] thymidine into acid-insoluble DNAase-sensitive material and the cytoplasmic location established by cell fractionation and electron microscope radioautographic methods. A minimum of 10 plaque-forming units per cell of RV14 was required to stimulate DNA synthesis which did not occur above 34.5 degrees C,  a temperature optimal for virus replication. Cytoplasmic DNA taken from RV14-infected or control cells could be differentiated from the bulk of cell (nuclear) DNA by several criteria, including: (1) RV14 induction of synthesis; (2) lower buoyant density and greater heterogeneity in CsCl and ethidium bromide/CsCl gradients; and (3) a different kinetic complexity upon reannealing. The Cot 1/2 value of cytoplasmic DNA, calclated as 50--100 from reassociation profiles, was about 10-fold less complex than the Cot 1/2 value of nuclear DNA (800-1000). These data rule out the possibility that cytoplasmic DNA arises by random breakage of nuclear DNA during cell disruption and extraction and are compatible with the  hypothesis that inoculation of KB cells with RV14 results in stimulation of synthesis of a specific class of cell DNA which is detected in the cytoplasm.", "contents": "Cytoplasmic DNA synthesis in rhinovirus type 14-inoculated  KB cells. Rhinovirus type 14 (RV14) incuced a transient statistically significant stimulation in synthesis of DNA which appeared between 0 and 3 h post-inoculation in the cytoplasm of high density monolayer cultures of KB cells. Newly synthesized DNA was measured by incorporation of [3H] thymidine into acid-insoluble DNAase-sensitive material and the cytoplasmic location established by cell fractionation and electron microscope radioautographic methods. A minimum of 10 plaque-forming units per cell of RV14 was required to stimulate DNA synthesis which did not occur above 34.5 degrees C,  a temperature optimal for virus replication. Cytoplasmic DNA taken from RV14-infected or control cells could be differentiated from the bulk of cell (nuclear) DNA by several criteria, including: (1) RV14 induction of synthesis; (2) lower buoyant density and greater heterogeneity in CsCl and ethidium bromide/CsCl gradients; and (3) a different kinetic complexity upon reannealing. The Cot 1/2 value of cytoplasmic DNA, calclated as 50--100 from reassociation profiles, was about 10-fold less complex than the Cot 1/2 value of nuclear DNA (800-1000). These data rule out the possibility that cytoplasmic DNA arises by random breakage of nuclear DNA during cell disruption and extraction and are compatible with the  hypothesis that inoculation of KB cells with RV14 results in stimulation of synthesis of a specific class of cell DNA which is detected in the cytoplasm."}
{"id": "PMID:208616", "title": "Polysomes and polysomal mRNAs in SV40-infected CV-1 cells. In vivo observations.", "content": "SV40-specific polysomes are relatively larger than host polysomes. Both 16 S and 19 S virus-specific late mRNAs are found associated with these polysomes and they are present in a ratio of approximately 2 : 1. The rates at which these virus-specific mRNAs are translated are the same, so that the relative amounts of virus-specific polypeptides synthesized in the virus-infected cells is determined by the relative amounts of 16 S and 19 S mRNAs coding for them.", "contents": "Polysomes and polysomal mRNAs in SV40-infected CV-1 cells. In vivo observations. SV40-specific polysomes are relatively larger than host polysomes. Both 16 S and 19 S virus-specific late mRNAs are found associated with these polysomes and they are present in a ratio of approximately 2 : 1. The rates at which these virus-specific mRNAs are translated are the same, so that the relative amounts of virus-specific polypeptides synthesized in the virus-infected cells is determined by the relative amounts of 16 S and 19 S mRNAs coding for them."}
{"id": "PMID:208617", "title": "Purification and properties of methanol dehydrogenase from Hyphomicrobium x.", "content": "(1) A method for the isolation of methanol dehydrogenase (alcohol:(acceptor) oxidoreductase, EC 1.1.99.8) from Hyphomicrobium X is decribed. The purified enzyme was resolved by polyacrylamide gel electrophoresis into one main and two minor active bands. Iron and manganese were the only detected metals in the enzyme preparation. (2) The substrate, methanol, was oxidized to formic acid by a stoichiometric amount of artificial electron acceptor. During the reaction, no free formaldehyde could be detected. Other primary alcohols were oxidized to the corresponding aldehydes were a poor substrate or no substrate at all. (3) Some new and efficient one-electron acceptors were found. With these electron acceptors, the enzyme had a high pH optimum and ammonia was still required in the assay system. (4) ESR spectroscopy showed the presence of an enzyme-bound organic free radical. With X-band ESR the signal had a peak-to-peak linewidth of about 0.7 mT. The signal was further resolved by Q-band ESR and the values gparallel = 2.0024 and gperpendicular = 2.0056 were derived. (5) Under denaturing conditions the ESR signal and enzymatic activity disappeared at the same time as fluorescence appeared. Enzymatic activity is not restored when extracted cofactor and apoenzyme are brought together under normal conditions. Some properties of the unusual prosthetic group are presented in a preliminary form.", "contents": "Purification and properties of methanol dehydrogenase from Hyphomicrobium x. (1) A method for the isolation of methanol dehydrogenase (alcohol:(acceptor) oxidoreductase, EC 1.1.99.8) from Hyphomicrobium X is decribed. The purified enzyme was resolved by polyacrylamide gel electrophoresis into one main and two minor active bands. Iron and manganese were the only detected metals in the enzyme preparation. (2) The substrate, methanol, was oxidized to formic acid by a stoichiometric amount of artificial electron acceptor. During the reaction, no free formaldehyde could be detected. Other primary alcohols were oxidized to the corresponding aldehydes were a poor substrate or no substrate at all. (3) Some new and efficient one-electron acceptors were found. With these electron acceptors, the enzyme had a high pH optimum and ammonia was still required in the assay system. (4) ESR spectroscopy showed the presence of an enzyme-bound organic free radical. With X-band ESR the signal had a peak-to-peak linewidth of about 0.7 mT. The signal was further resolved by Q-band ESR and the values gparallel = 2.0024 and gperpendicular = 2.0056 were derived. (5) Under denaturing conditions the ESR signal and enzymatic activity disappeared at the same time as fluorescence appeared. Enzymatic activity is not restored when extracted cofactor and apoenzyme are brought together under normal conditions. Some properties of the unusual prosthetic group are presented in a preliminary form."}
{"id": "PMID:208618", "title": "Purification of four pyruvate kinase isozymes of rats by affinity elution chromatography.", "content": "1. Purification of four isozymes of pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) L, M1, M2 and R was much improved to give good yields by affinity elution chromatography. The enzyme was eluted from a phosphocellulose column with 0.5 mM phosphoenolpyruvate. Types L, M2 and R were stabilized with fructose 1,6-diphosphate throughout the purification procedures. 2. The isozymes were crystallized under various conditions: types L and R were readily crystallized from medium of low ionic strength, types L, M1, and M2 were crystallized from ammonium sulfate solution in different forms in the presence and absence of phosphoenolpyruvate. Type M1 was also crystallized in different forms in the presence and absence of fructose 1,6-diphosphate. 3. Amino acid analyses showed that the compositions of types L and R, and of types M1 and M2, respectively, were very similar.", "contents": "Purification of four pyruvate kinase isozymes of rats by affinity elution chromatography. 1. Purification of four isozymes of pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) L, M1, M2 and R was much improved to give good yields by affinity elution chromatography. The enzyme was eluted from a phosphocellulose column with 0.5 mM phosphoenolpyruvate. Types L, M2 and R were stabilized with fructose 1,6-diphosphate throughout the purification procedures. 2. The isozymes were crystallized under various conditions: types L and R were readily crystallized from medium of low ionic strength, types L, M1, and M2 were crystallized from ammonium sulfate solution in different forms in the presence and absence of phosphoenolpyruvate. Type M1 was also crystallized in different forms in the presence and absence of fructose 1,6-diphosphate. 3. Amino acid analyses showed that the compositions of types L and R, and of types M1 and M2, respectively, were very similar."}
{"id": "PMID:208619", "title": "The acceleration of methanesulfonylation of acetylcholinesterase with cationic accelerators as an electrostatic effect.", "content": "1. In order to check our hypothesis of the electrostatic nature of the acceleration of methanesulfonylation of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) with cationic accelerators, equations were solved for methane-sulfonylation with two accelerators and the reaction was studied in the presence of some single accelerators, including the sodium cation, and in the presence of two acclerators simultaneously. 2. The second-order rate constants for methanesulfonylation of the complexes between the enzyme and accelerators decamethonium, tetraethylammonium and tetramethylammonium are 90, 88 and 17 1 - mol-1 - s-1, respectively, which corresponds to a maximal acceleration of 29, 28 and 5.5 times, respectively. The dissociation constants for the binding of these accelerators to the enzyme, obtained from our acceleration experiments, are 3.7 - 10(-6), 3.2 - 10(-4) and 1.4 - 10(-3) M, respectively. These values are in good agreement with the dissociation constants of these ligands as inhibitors of acetylcholinesterase. It is interesting to note that the sodium cation also accelerates the methane-sulfonylation up to around three times, the corresponding second-order rate constant and the dissociation constant being 10 1 - mol-1 - s-1 and 1.3 M, respectively. 3. All tested cations compete in the acceleration with each other; they seem to accelerate the reaction in the same way and from the same site, the catalytic anionic site. 4. These findings confirm the hypothesis of the electrostatic nature of acceleration.", "contents": "The acceleration of methanesulfonylation of acetylcholinesterase with cationic accelerators as an electrostatic effect. 1. In order to check our hypothesis of the electrostatic nature of the acceleration of methanesulfonylation of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) with cationic accelerators, equations were solved for methane-sulfonylation with two accelerators and the reaction was studied in the presence of some single accelerators, including the sodium cation, and in the presence of two acclerators simultaneously. 2. The second-order rate constants for methanesulfonylation of the complexes between the enzyme and accelerators decamethonium, tetraethylammonium and tetramethylammonium are 90, 88 and 17 1 - mol-1 - s-1, respectively, which corresponds to a maximal acceleration of 29, 28 and 5.5 times, respectively. The dissociation constants for the binding of these accelerators to the enzyme, obtained from our acceleration experiments, are 3.7 - 10(-6), 3.2 - 10(-4) and 1.4 - 10(-3) M, respectively. These values are in good agreement with the dissociation constants of these ligands as inhibitors of acetylcholinesterase. It is interesting to note that the sodium cation also accelerates the methane-sulfonylation up to around three times, the corresponding second-order rate constant and the dissociation constant being 10 1 - mol-1 - s-1 and 1.3 M, respectively. 3. All tested cations compete in the acceleration with each other; they seem to accelerate the reaction in the same way and from the same site, the catalytic anionic site. 4. These findings confirm the hypothesis of the electrostatic nature of acceleration."}
{"id": "PMID:208620", "title": "Characterization of multiple forms of histone phosphatase in rat liver.", "content": "By using chromatography on DEAE-cellulose, aminohexyl-Sepharose 4B and Sephadex G-200, rat liver extract was shown to contain at least three fractions, IA, IB and II, of histone phosphatase. Fractions IA and II are probably the same enzymes as the previously described glycogen synthase phosphatase and phosphorylase phosphatase, respectively, but IB exhibits noticeable activities only with phosphohistone as substrate. Approximate molecular weights of 69 000, 300 000 and 160 000 were determined by gel filtration on Sephadex G-200 for IA, IB and II, respectively.", "contents": "Characterization of multiple forms of histone phosphatase in rat liver. By using chromatography on DEAE-cellulose, aminohexyl-Sepharose 4B and Sephadex G-200, rat liver extract was shown to contain at least three fractions, IA, IB and II, of histone phosphatase. Fractions IA and II are probably the same enzymes as the previously described glycogen synthase phosphatase and phosphorylase phosphatase, respectively, but IB exhibits noticeable activities only with phosphohistone as substrate. Approximate molecular weights of 69 000, 300 000 and 160 000 were determined by gel filtration on Sephadex G-200 for IA, IB and II, respectively."}
{"id": "PMID:208621", "title": "Dissociated active subunits of tobacco phosphodiesterase.", "content": "The tetrameric nature of the phosphodiesterase isolated from tobacco cells is confirmed by determining the number of oligomers formed upon cross-linking the enzyme with dimethyl suberimidate. The isolation of the catalytically active monomer, which is formed by incubating the enzyme with urea and 2-mercaptoethanol, has been accomplished by gel filtration on Sephadex G-200. The isolated monomer of the phosphodiesterase is stable under nondenaturing conditions and catalytically active. The enzyme activity of the phosphodiesterase monomer is more sensitive to SDS than the tetramer. The phosphodiesterase tetramer exhibits characteristics of negative cooperativity, while the isolated monomer does not.", "contents": "Dissociated active subunits of tobacco phosphodiesterase. The tetrameric nature of the phosphodiesterase isolated from tobacco cells is confirmed by determining the number of oligomers formed upon cross-linking the enzyme with dimethyl suberimidate. The isolation of the catalytically active monomer, which is formed by incubating the enzyme with urea and 2-mercaptoethanol, has been accomplished by gel filtration on Sephadex G-200. The isolated monomer of the phosphodiesterase is stable under nondenaturing conditions and catalytically active. The enzyme activity of the phosphodiesterase monomer is more sensitive to SDS than the tetramer. The phosphodiesterase tetramer exhibits characteristics of negative cooperativity, while the isolated monomer does not."}
{"id": "PMID:208622", "title": "Canine pulmonary angiotensin-converting enzyme. Physicochemical, catalytic and immunological properties.", "content": "Antiontensin-converting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1) has been solubilized from canine pulmonary particles and purified to apparent homogeneity. A value of approx. 140000 was estimated for the molecular weight of the native and the reduced, denatured forms of the enzyme. No free NH2-terminal residue was detected by the dansylation procedure. Carbohydrate accounted for 17% of the weight of the enzyme, and the major residues were galactose, mannose and N-acetylglucosamine with smaller amounts of sialic acid and fucose. Removal of sialic acid residues with neuraminidase did not alter enzymatic activity. The enzyme contained one molar equivalent of zinc. Addition of this metal reversed stimulation and inhibition of activity observed in the presence of Co2+ and Mn2+, respectively. Immunologic homology of pure dog and rabbit enzymes was demonstrable with goat antisera. Fab fragments and intact IgG antibodies displayed similar inhibition dose vs. response curves with homologous enzyme, whereas the fragments were poor inhibitors of heterologous activity compared to the holoantibodies. The canine glycoprotein was much less active than the rabbit preparation in catalyzing hydrolysis of Hip-His-Leu. In contrast, the two enzymes exhibited comparable kinetic parameters with angiotensin I as substrate.", "contents": "Canine pulmonary angiotensin-converting enzyme. Physicochemical, catalytic and immunological properties. Antiontensin-converting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1) has been solubilized from canine pulmonary particles and purified to apparent homogeneity. A value of approx. 140000 was estimated for the molecular weight of the native and the reduced, denatured forms of the enzyme. No free NH2-terminal residue was detected by the dansylation procedure. Carbohydrate accounted for 17% of the weight of the enzyme, and the major residues were galactose, mannose and N-acetylglucosamine with smaller amounts of sialic acid and fucose. Removal of sialic acid residues with neuraminidase did not alter enzymatic activity. The enzyme contained one molar equivalent of zinc. Addition of this metal reversed stimulation and inhibition of activity observed in the presence of Co2+ and Mn2+, respectively. Immunologic homology of pure dog and rabbit enzymes was demonstrable with goat antisera. Fab fragments and intact IgG antibodies displayed similar inhibition dose vs. response curves with homologous enzyme, whereas the fragments were poor inhibitors of heterologous activity compared to the holoantibodies. The canine glycoprotein was much less active than the rabbit preparation in catalyzing hydrolysis of Hip-His-Leu. In contrast, the two enzymes exhibited comparable kinetic parameters with angiotensin I as substrate."}
{"id": "PMID:208624", "title": "Effects of various ligands on interaction of AMP deaminase with myosin.", "content": "Purified rat muscle AMP deaminase (AMP aminohydrolase, EC 3.5.4.6) binds tightly to rat myosin. The binding is abolished in the presence of low concentrations of various ligands. Pyrophosphate and GTP at concentrations as low as 0.1 micrometer were effective in abolishing the interaction between two proteins. Other nucleoside triphosphates were less effective than GTP and the concentrations required for 50% inhibition were approximately 0.3 to 0.7 micrometer. ADP and AMP are effective in inhibiting the interaction between two proteins, but they are less effective than the nucleoside triphosphates; 50% inhibition occurred at 34 micrometer with ADP and at 1 mM with AMP. Creatine phosphate and inorganic phosphate showed 50% inhibition at 5 to 6 mM. All of the compounds, which affected AMP deaminase activity, were effective in abolishing the interaction of the enzyme with myosin; however, the interaction-abolishing effects of the compounds are not parallel with their inhibitory effects on the deaminase activity. Although there exist three parental isozymes of AMP deaminase in the rat, all three enzymes interacted with myosin.", "contents": "Effects of various ligands on interaction of AMP deaminase with myosin. Purified rat muscle AMP deaminase (AMP aminohydrolase, EC 3.5.4.6) binds tightly to rat myosin. The binding is abolished in the presence of low concentrations of various ligands. Pyrophosphate and GTP at concentrations as low as 0.1 micrometer were effective in abolishing the interaction between two proteins. Other nucleoside triphosphates were less effective than GTP and the concentrations required for 50% inhibition were approximately 0.3 to 0.7 micrometer. ADP and AMP are effective in inhibiting the interaction between two proteins, but they are less effective than the nucleoside triphosphates; 50% inhibition occurred at 34 micrometer with ADP and at 1 mM with AMP. Creatine phosphate and inorganic phosphate showed 50% inhibition at 5 to 6 mM. All of the compounds, which affected AMP deaminase activity, were effective in abolishing the interaction of the enzyme with myosin; however, the interaction-abolishing effects of the compounds are not parallel with their inhibitory effects on the deaminase activity. Although there exist three parental isozymes of AMP deaminase in the rat, all three enzymes interacted with myosin."}
{"id": "PMID:208625", "title": "Reversible in activation of purified (Na+ + K+)-ATPase from human renal tissue by cyclic AMP-dependent protein kinase.", "content": "Human renal (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) preparations which exhibited a non-linear reaction rate, contained high levels of membrane-bound cyclic AMP-dependent protein kinase, while this latter activity was much less or absent in purified preparations. A non-linear reaction rate was observed in a purified preparation of (Na+ + K+)-ATPase by reconstituting the enzyme into lipid vesicles with cyclic AMP-dependent protein kinase. The addition of cyclic AMP to the ATPase assay of these lipid vesicles inactivated the (Na+ + K+)-ATPase. The cytoplasmic fraction of the cell contained a nondialyzable factor, which prevented (or reversed) the cyclic AMP-mediated inactivation of the enzyme.", "contents": "Reversible in activation of purified (Na+ + K+)-ATPase from human renal tissue by cyclic AMP-dependent protein kinase. Human renal (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) preparations which exhibited a non-linear reaction rate, contained high levels of membrane-bound cyclic AMP-dependent protein kinase, while this latter activity was much less or absent in purified preparations. A non-linear reaction rate was observed in a purified preparation of (Na+ + K+)-ATPase by reconstituting the enzyme into lipid vesicles with cyclic AMP-dependent protein kinase. The addition of cyclic AMP to the ATPase assay of these lipid vesicles inactivated the (Na+ + K+)-ATPase. The cytoplasmic fraction of the cell contained a nondialyzable factor, which prevented (or reversed) the cyclic AMP-mediated inactivation of the enzyme."}
{"id": "PMID:208627", "title": "Steric and charge factors in the resistance of uridylyl(3' - 5')N6-(N-threonylcarbonyl)adenosine to venom phosphodiesterase hydrolysis.", "content": "The contribution of steric and negative charge factors to the resistance of uridylyl(3' - 5')N6-(N-threonylcarbonyl)adenosine to venom phosphodiesterase was investigated. The hydrolysis rates of uridylyl(3'-5')N6-(N-threonylcarbonyl)-adenosine, its model derivatives, methyl ester and O-benzyl ester, together with unmodified uridyly (3'-5')adenosine, were studied. It was found that the contribution of both factors is of the same order. The steric inhibition of digestion is distinctly higher than that confirmed by N6-(delta2-isopentenyl)adenosine [1], which is ascribed to the rigid conformation of the threonylcarbonyladenosine side chain.", "contents": "Steric and charge factors in the resistance of uridylyl(3' - 5')N6-(N-threonylcarbonyl)adenosine to venom phosphodiesterase hydrolysis. The contribution of steric and negative charge factors to the resistance of uridylyl(3' - 5')N6-(N-threonylcarbonyl)adenosine to venom phosphodiesterase was investigated. The hydrolysis rates of uridylyl(3'-5')N6-(N-threonylcarbonyl)-adenosine, its model derivatives, methyl ester and O-benzyl ester, together with unmodified uridyly (3'-5')adenosine, were studied. It was found that the contribution of both factors is of the same order. The steric inhibition of digestion is distinctly higher than that confirmed by N6-(delta2-isopentenyl)adenosine [1], which is ascribed to the rigid conformation of the threonylcarbonyladenosine side chain."}
{"id": "PMID:208629", "title": "Lipoprotein and cholesterol metabolism in rabbit arterial endothelial cells in culture.", "content": "Like all other peripheral cells types thus far studied in culture, endothelial cells derived from the rabbit aorta bind, internalize and degrade low density lipoprotein (LDL) at a significant rate. At any given LDL concentration, the metabolism by rabbit endothelial cells was slower than that by fibroblasts or smooth muscle cells. Thus, longer incubations were required to achieve a net increment in cell cholesterol content or to suppress endogenous sterol synthesis; after 18-24 h incubation in the presence of LDL at 100 microgram LDL protein/ml inhibition was greater than 80% relative to the rate in cells incubated in the absence of lipoproteins. High density lipoproteins (HDL) were also taken up and degraded but did not inhibit sterol synthesis. Studies of LDL binding to the cell surface suggested the presence of at least two classes of binding sites; the high-affinity binding sites were fully saturated at very low LDL concentrations (about 5 microgram LDL protein/ml). However, the degree of inhibition of endogenous sterol synthesis increased progressively with increasing LDL concentrations from 5 to 100 microgram LDL/ml, suggesting that uptake from the low affinity sites in this cell line contributes to the suppression of endogenous sterol synthesis. The internalization and degradation of LDL also increased with concentrations as high as 700 microgram/ml. Thus, in vivo, where the cells are exposed to LDL concentrations far above that needed to saturate the high affinity sites, most of the LDL degradation would be attributable to LDL taken up from low affinity sites. As noted previously in swine arterial smooth muscle cells and in human skin fibroblasts, unlabeled HDL reduced the binding, internalization and degradation of labeled LDL. Cells incubated for 24 h in the presence of high concentrations of LDL alone showed a net increment in cell cholesterol content; the simultaneous presence of HDL in the medium significantly reduced this LDL-induced increment in cell cholesterol content. The possible relationship between LDL uptake and degradation by these cells in vitro is discussed in relationship to their transport function in vivo.", "contents": "Lipoprotein and cholesterol metabolism in rabbit arterial endothelial cells in culture. Like all other peripheral cells types thus far studied in culture, endothelial cells derived from the rabbit aorta bind, internalize and degrade low density lipoprotein (LDL) at a significant rate. At any given LDL concentration, the metabolism by rabbit endothelial cells was slower than that by fibroblasts or smooth muscle cells. Thus, longer incubations were required to achieve a net increment in cell cholesterol content or to suppress endogenous sterol synthesis; after 18-24 h incubation in the presence of LDL at 100 microgram LDL protein/ml inhibition was greater than 80% relative to the rate in cells incubated in the absence of lipoproteins. High density lipoproteins (HDL) were also taken up and degraded but did not inhibit sterol synthesis. Studies of LDL binding to the cell surface suggested the presence of at least two classes of binding sites; the high-affinity binding sites were fully saturated at very low LDL concentrations (about 5 microgram LDL protein/ml). However, the degree of inhibition of endogenous sterol synthesis increased progressively with increasing LDL concentrations from 5 to 100 microgram LDL/ml, suggesting that uptake from the low affinity sites in this cell line contributes to the suppression of endogenous sterol synthesis. The internalization and degradation of LDL also increased with concentrations as high as 700 microgram/ml. Thus, in vivo, where the cells are exposed to LDL concentrations far above that needed to saturate the high affinity sites, most of the LDL degradation would be attributable to LDL taken up from low affinity sites. As noted previously in swine arterial smooth muscle cells and in human skin fibroblasts, unlabeled HDL reduced the binding, internalization and degradation of labeled LDL. Cells incubated for 24 h in the presence of high concentrations of LDL alone showed a net increment in cell cholesterol content; the simultaneous presence of HDL in the medium significantly reduced this LDL-induced increment in cell cholesterol content. The possible relationship between LDL uptake and degradation by these cells in vitro is discussed in relationship to their transport function in vivo."}
{"id": "PMID:208631", "title": "Differential effects of isolated lipoproteins from normal and hypercholesterolemic rhesus monkeys on cholesterol esterification and accumulation in arterial smooth muscle cells in culture.", "content": "Whole serum obtained from hypercholesterolemic rhesus monkeys was found to stimulate cholesterol esterification and cholesteryl ester accumulation in rhesus monkey arterial smooth muscle cells in culture to a significantly greater extent than normocholesterolemic serum. This was true even when the cholesterol concentration of the culture medium was equalized. Isolation and characterzation of the low density lipoproteins (LDL) from rhesus monkeys indicated that the LDL from hypercholesterolemic animals was 33% larger than LDL from normocholesterolemic animals due principally to an increase in the amount of cholesteryl ester per molecule. As a result, LDL from hypercholesterolemic animals transported over 50% more cholesterol per molecule than did normal LDL. The LDL of altered composition from hypercholesterolemic animals, when added to smooth muscle cells in culture, was nearly twice as effective in stimulating cholesterol esterification and cholesteryl ester accumulation than was LDL of normal composition. Results suggest that at least part of the exaggerated ability of whole hypercholesterolemic serum to stimulate the esterification and accumulation of cholesterol in cells in culture is due to the presence of LDL of altered composition.", "contents": "Differential effects of isolated lipoproteins from normal and hypercholesterolemic rhesus monkeys on cholesterol esterification and accumulation in arterial smooth muscle cells in culture. Whole serum obtained from hypercholesterolemic rhesus monkeys was found to stimulate cholesterol esterification and cholesteryl ester accumulation in rhesus monkey arterial smooth muscle cells in culture to a significantly greater extent than normocholesterolemic serum. This was true even when the cholesterol concentration of the culture medium was equalized. Isolation and characterzation of the low density lipoproteins (LDL) from rhesus monkeys indicated that the LDL from hypercholesterolemic animals was 33% larger than LDL from normocholesterolemic animals due principally to an increase in the amount of cholesteryl ester per molecule. As a result, LDL from hypercholesterolemic animals transported over 50% more cholesterol per molecule than did normal LDL. The LDL of altered composition from hypercholesterolemic animals, when added to smooth muscle cells in culture, was nearly twice as effective in stimulating cholesterol esterification and cholesteryl ester accumulation than was LDL of normal composition. Results suggest that at least part of the exaggerated ability of whole hypercholesterolemic serum to stimulate the esterification and accumulation of cholesterol in cells in culture is due to the presence of LDL of altered composition."}
{"id": "PMID:208632", "title": "In vivo uptake of human and rat low density and high density lipoprotein by parenchymal and nonparenchymal cells from rat liver.", "content": "The relative contribution of the parenchymal and nonparenchymal rat liver cells to the hepatic uptake of human and rat high density lipoprotein (HDL) and low density lipoprotein (LDL) was determined in vivo. Nonparenchymal cells, isolated 6 h after intravenous injection of iodinated human HDL and LDL, contained respectively 4.2 and 6.3 times the amount of trichloroacetic acid-precipitable radioactivity per mg cell protein as compared to parenchymal cells. For rat iodinated HDL and LDL these factors were 3.4 and 4.1, respectively. These results indicate that nonparenchymal liver cells play a substantial role in the hepatic uptake of human and rat HDL and LDL in vivo.", "contents": "In vivo uptake of human and rat low density and high density lipoprotein by parenchymal and nonparenchymal cells from rat liver. The relative contribution of the parenchymal and nonparenchymal rat liver cells to the hepatic uptake of human and rat high density lipoprotein (HDL) and low density lipoprotein (LDL) was determined in vivo. Nonparenchymal cells, isolated 6 h after intravenous injection of iodinated human HDL and LDL, contained respectively 4.2 and 6.3 times the amount of trichloroacetic acid-precipitable radioactivity per mg cell protein as compared to parenchymal cells. For rat iodinated HDL and LDL these factors were 3.4 and 4.1, respectively. These results indicate that nonparenchymal liver cells play a substantial role in the hepatic uptake of human and rat HDL and LDL in vivo."}
{"id": "PMID:208633", "title": "M\u00f6ssbauer study of cytochrome c2 from Rhodospirillum rubrum. Sign of the product gxgygz of some low spin ferric heme proteins.", "content": "We have studied cytochrome c2 from Rhodospirllum rubrum with M\u00f6ssbauer spectroscopy and electron paramagnetic resonance. The M\u00f6ssbauer data on the ferric protein, taken in external magnetic fields up to 50 kG, were analyzed within the framework of the ligand field model commonly used to evaluate low-spin ferric heme compounds. The data analysis shows that the determinant of the electronic g-tensor, i.e. the product gxgygz, is positive for cytochrome c2. We have reanalyzed published M\u00f6ssbauer data of some low-spin ferric heme proteins with respect to the sign of the g-tensor determinant. We find that gxgygz is also positive for the cytochromes c, bs, and P-450, and for chloroperoxidase.", "contents": "M\u00f6ssbauer study of cytochrome c2 from Rhodospirillum rubrum. Sign of the product gxgygz of some low spin ferric heme proteins. We have studied cytochrome c2 from Rhodospirllum rubrum with M\u00f6ssbauer spectroscopy and electron paramagnetic resonance. The M\u00f6ssbauer data on the ferric protein, taken in external magnetic fields up to 50 kG, were analyzed within the framework of the ligand field model commonly used to evaluate low-spin ferric heme compounds. The data analysis shows that the determinant of the electronic g-tensor, i.e. the product gxgygz, is positive for cytochrome c2. We have reanalyzed published M\u00f6ssbauer data of some low-spin ferric heme proteins with respect to the sign of the g-tensor determinant. We find that gxgygz is also positive for the cytochromes c, bs, and P-450, and for chloroperoxidase."}
{"id": "PMID:208634", "title": "Cellular cyclic AMP in dispersed mucosal cells from guinea pig stomach.", "content": "In dispersed mucosal cells from guinea pig stomach cyclic AMP was increased 4-fold by theophylline, 5-fold by prostaglandin E2, and 10- to 15-fold by histamine. Theophylline augmented the increase in cellular cyclic AMP caused by histamine or prostaglandin E1 and the actions of histamine and prostaglandin E1 were additive. Cellular cyclic AMP was not altered by carbachol, gastrin, secretin, vasoactive intestinal peptide, glucagon, insulin or the octapeptide of cholecystokinin. Metiamide or diphenhydramine but not atropine inhibited the increase in cellular cyclic AMP caused by histamine, but did not alter the concentration of cyclic AMP in control cells or in cells incubated with theophylline or prostaglandin E1.", "contents": "Cellular cyclic AMP in dispersed mucosal cells from guinea pig stomach. In dispersed mucosal cells from guinea pig stomach cyclic AMP was increased 4-fold by theophylline, 5-fold by prostaglandin E2, and 10- to 15-fold by histamine. Theophylline augmented the increase in cellular cyclic AMP caused by histamine or prostaglandin E1 and the actions of histamine and prostaglandin E1 were additive. Cellular cyclic AMP was not altered by carbachol, gastrin, secretin, vasoactive intestinal peptide, glucagon, insulin or the octapeptide of cholecystokinin. Metiamide or diphenhydramine but not atropine inhibited the increase in cellular cyclic AMP caused by histamine, but did not alter the concentration of cyclic AMP in control cells or in cells incubated with theophylline or prostaglandin E1."}
{"id": "PMID:208636", "title": "Characterization of the oligosaccharide side chain of apolipoprotein C-III from human plasma very low density lipoproteins.", "content": "Apolipoprotein C-III1 and apolipoprotein C-III2 each contain one oligosaccharide side chain, bound O-glycosidically to threonine in position 74 of the amino acid sequence. The studies reported in this paper characterize these alkali labile oligosaccharides, thereby demonstrating the complete structure of apolipoprotein C-III. Monosaccharide analysis revealed the following sugar composition: D-galactose/N-acetyl-D-galactosamine/sialic acid 1 : 1 : 1 and 1 : 1 : 2 for apolipoprotein C-III1 and apolipoprotein C-III2, respectively. Treatment of desialylated apolipoproteins with alkaline borohydride released the reduced disaccharide beta-D-galactosyl-(1 leads to 3)-N-acetyl-D-galactosaminitol, which was detected by gas-liquid chromatography. Further studies employing periodate oxidation and Smith degradation indicated that the structure of the trisaccharide from apolipoprotein C-III1 was alpha-N-acetylneuraminyl-(2 leads to 3)-beta-D-galactosyl-(1 leads to 3)-N-acetyl-D-galactosaminitol. The tetrasaccharide structure from apolipoprotein C-III2 is made up of this trisaccharide plus one sialic acid residue linked to C6 of N-acetyl-D-galactosaminitol, as was shown by the assessment of chromogens formed upon alkaline degradation.", "contents": "Characterization of the oligosaccharide side chain of apolipoprotein C-III from human plasma very low density lipoproteins. Apolipoprotein C-III1 and apolipoprotein C-III2 each contain one oligosaccharide side chain, bound O-glycosidically to threonine in position 74 of the amino acid sequence. The studies reported in this paper characterize these alkali labile oligosaccharides, thereby demonstrating the complete structure of apolipoprotein C-III. Monosaccharide analysis revealed the following sugar composition: D-galactose/N-acetyl-D-galactosamine/sialic acid 1 : 1 : 1 and 1 : 1 : 2 for apolipoprotein C-III1 and apolipoprotein C-III2, respectively. Treatment of desialylated apolipoproteins with alkaline borohydride released the reduced disaccharide beta-D-galactosyl-(1 leads to 3)-N-acetyl-D-galactosaminitol, which was detected by gas-liquid chromatography. Further studies employing periodate oxidation and Smith degradation indicated that the structure of the trisaccharide from apolipoprotein C-III1 was alpha-N-acetylneuraminyl-(2 leads to 3)-beta-D-galactosyl-(1 leads to 3)-N-acetyl-D-galactosaminitol. The tetrasaccharide structure from apolipoprotein C-III2 is made up of this trisaccharide plus one sialic acid residue linked to C6 of N-acetyl-D-galactosaminitol, as was shown by the assessment of chromogens formed upon alkaline degradation."}
{"id": "PMID:208637", "title": "Studies on the utilization of ferritin iron in the ferrochelatase reaction of isolated rat liver mitochondria.", "content": "The utilization of ferritin as a source of iron for the ferrochelatase reaction has been studied in isolated rat liver mitochondria. 1. It was found that isolated rat liver mitochondria utilized ferritin as a source of iron for the ferrochelatase reaction in the presence of succinate plus FMN (or FAD). 2. Under optimal experimental conditions, i.e., approx. 50 micromol/1 FMN, 37 degrees C, pH 7.4 and 0.5 mmol/l Fe(III) (as ferritin iron), the release process, as shown by the formation of deuteroheme, amounted to approx. 0.5 nmol iron/min per mg protein. 3. The release process could not be elicited by ultrasonically treated mitochondria, lysosomes, microsomes or cytosol, i.e., the release of iron from ferritin was due to mitochondria and was a function of the in situ orientation of the mitochondrial inner membrane. 4. The release of iron from ferritin by the mitochrondria might be of relevance not only for the in situ synthesis of heme in the hepatocyte, but also with respect to the mechanism(s) by means of which iron is mobilized for transport to the erythroid tissue.", "contents": "Studies on the utilization of ferritin iron in the ferrochelatase reaction of isolated rat liver mitochondria. The utilization of ferritin as a source of iron for the ferrochelatase reaction has been studied in isolated rat liver mitochondria. 1. It was found that isolated rat liver mitochondria utilized ferritin as a source of iron for the ferrochelatase reaction in the presence of succinate plus FMN (or FAD). 2. Under optimal experimental conditions, i.e., approx. 50 micromol/1 FMN, 37 degrees C, pH 7.4 and 0.5 mmol/l Fe(III) (as ferritin iron), the release process, as shown by the formation of deuteroheme, amounted to approx. 0.5 nmol iron/min per mg protein. 3. The release process could not be elicited by ultrasonically treated mitochondria, lysosomes, microsomes or cytosol, i.e., the release of iron from ferritin was due to mitochondria and was a function of the in situ orientation of the mitochondrial inner membrane. 4. The release of iron from ferritin by the mitochrondria might be of relevance not only for the in situ synthesis of heme in the hepatocyte, but also with respect to the mechanism(s) by means of which iron is mobilized for transport to the erythroid tissue."}
{"id": "PMID:208639", "title": "Properties of beta-adrenergic receptors in untreated and butyrate-treated Hela cells.", "content": "HeLa cells contain receptors on their surface which are beta-adrenergic in nature. The binding of (-)-[3H]dihydroalprenolol is rapid, reversible, stereospecific and of relatively high affinity. The HeLa cells also contain an adenylate cyclase which is activated by (-)-isoproterenol greater than (-)-epinephrine greater than (-)-norepinephrine. The adenylate cyclase of HeLa is also activated by guanyl-5'-ylimidodophosphate (Gpp(NH)p), a nonhydrolyzable analogue of GTP. Inclusion of both (-)-isoproterenol and Gpp(NH)p leads to approximately additive rather than synergistic activation of adenylate cyclase. After treatment of HeLa cells with 5mM sodium butyrate there is an increase in the number of beta-adrenergic receptors, but not in their affinity, which is reflected in an increased ability of (-)-isoproterenol to activate adenylate cyclase. Other properties of the beta-adrenergic receptor including association and dissociation rates, temperature optimum of adenylate cyclase and response to Gpp(NH)p are relatively unaffected by butyrate pretreatment of the cells.", "contents": "Properties of beta-adrenergic receptors in untreated and butyrate-treated Hela cells. HeLa cells contain receptors on their surface which are beta-adrenergic in nature. The binding of (-)-[3H]dihydroalprenolol is rapid, reversible, stereospecific and of relatively high affinity. The HeLa cells also contain an adenylate cyclase which is activated by (-)-isoproterenol greater than (-)-epinephrine greater than (-)-norepinephrine. The adenylate cyclase of HeLa is also activated by guanyl-5'-ylimidodophosphate (Gpp(NH)p), a nonhydrolyzable analogue of GTP. Inclusion of both (-)-isoproterenol and Gpp(NH)p leads to approximately additive rather than synergistic activation of adenylate cyclase. After treatment of HeLa cells with 5mM sodium butyrate there is an increase in the number of beta-adrenergic receptors, but not in their affinity, which is reflected in an increased ability of (-)-isoproterenol to activate adenylate cyclase. Other properties of the beta-adrenergic receptor including association and dissociation rates, temperature optimum of adenylate cyclase and response to Gpp(NH)p are relatively unaffected by butyrate pretreatment of the cells."}
{"id": "PMID:208640", "title": "Solubilization of pituitary receptors for thyrotropin-releasing hormone.", "content": "Receptors for thyrotropin-releasing hormone were solubilized by Triton X-100. Membrane fractions from GH3 pituitary tumor cells were incubated with thyrotropin-releasing hormone in order to saturate specific receptor sites before the addition of detergent. The amount of protein-bound hormone solubilized by Triton X-100 was proportional to the fractional saturation of specific membrane receptors. Increasing detergent:protein ratios from 0.5 to 20 led to a progressive loss of hormone . receptor complex from membrane fractions with a concomitant increase in soluble protein-bound hormone. The soluble hormone . receptor complex was not retained by 0.22 micron filters and remained soluble after ultracentrifugation. Following incubation with high (2.5--10%) concentrations of Triton X-100 and other non-ionic detergents, or following repeated detergent extraction, at least 18% of specifically bound thyrotropin-releasing hormone remained associated with particulate material. Unlike the hormone receptor complex, the free hormone receptor was inactivated by Triton X-100. A 50% loss of binding activity was obtained with 0.01% Triton X-100, corresponding to a detergent:protein ratio of 0.033. The hormone . receptor complex was included in Sepharose 6B and exhibited an apparent Stoke radius of 46 A in buffers containing Triton X-100. The complex aggregated in detergent-free buffers. Soluble hormone receptors were separated from excess detergent and thyrotropin-releasing hormone by chromatography on DEAE-cellulose. Thyrotropin-releasing hormone dissociated from soluble receptors with a half-time of 120 min at 0 degrees C, while the membrane hormone . receptor complex was stable for up to 5 at 0 degrees C.", "contents": "Solubilization of pituitary receptors for thyrotropin-releasing hormone. Receptors for thyrotropin-releasing hormone were solubilized by Triton X-100. Membrane fractions from GH3 pituitary tumor cells were incubated with thyrotropin-releasing hormone in order to saturate specific receptor sites before the addition of detergent. The amount of protein-bound hormone solubilized by Triton X-100 was proportional to the fractional saturation of specific membrane receptors. Increasing detergent:protein ratios from 0.5 to 20 led to a progressive loss of hormone . receptor complex from membrane fractions with a concomitant increase in soluble protein-bound hormone. The soluble hormone . receptor complex was not retained by 0.22 micron filters and remained soluble after ultracentrifugation. Following incubation with high (2.5--10%) concentrations of Triton X-100 and other non-ionic detergents, or following repeated detergent extraction, at least 18% of specifically bound thyrotropin-releasing hormone remained associated with particulate material. Unlike the hormone receptor complex, the free hormone receptor was inactivated by Triton X-100. A 50% loss of binding activity was obtained with 0.01% Triton X-100, corresponding to a detergent:protein ratio of 0.033. The hormone . receptor complex was included in Sepharose 6B and exhibited an apparent Stoke radius of 46 A in buffers containing Triton X-100. The complex aggregated in detergent-free buffers. Soluble hormone receptors were separated from excess detergent and thyrotropin-releasing hormone by chromatography on DEAE-cellulose. Thyrotropin-releasing hormone dissociated from soluble receptors with a half-time of 120 min at 0 degrees C, while the membrane hormone . receptor complex was stable for up to 5 at 0 degrees C."}
{"id": "PMID:208641", "title": "Follitropin receptors in rat testis. Characterization with enzymatically 125I-labeled human follitropin.", "content": "The interaction between enzymatically radioiodinated human follitropin and the follitropin receptors in testis homogenate was investigated in immature and adult rats. The 125I-labeled human follitropin exhibited high binding activity with specific binding of up to 17% in the presence of an excess of testis homogenate. Approx. 50% of the bound hormone could be eluted at pH 5, and the receptor purified tracer exhibited a 3.6-fold increase in binding activity when compared with the original tracer preparation. Quantitative analysis of equilibrium binding data was performed with corrections for the measured specific activity and maximum binding activity of the tracer hormone. The equilibrium association constants (Ka) determined 24 degrees C were not significantly different in immature and adult rat testis, and the mean value for Ka was 3.9 . 10(9) M-1. At 37 degrees C, the Ka value obtained using immature rat testis was 1.3 . 10(10) M-1. The association of 125I-labeled human follitropin with immature rat testis homogenate was time and temperature dependent. In the presence of an excess of unlabeled hormone, 30--60% of the preformed hormone . receptor complex was dissociated after 24 h incubation. A specific and sensitive radioligand-receptor assay for follitropin was developed using immature rat testis homogenate. The minimum detectable dose of purified human follitropin was 0.6 ng, and human urinary and pituitary follitropin, ovine follitropin and pregnant mare serum gonadotropin reacted in the assay with equivalent slopes. The potencies of highly purified pregnent mare serum gonadotropin and highly purified human  follitropin were similar in the radioligand-receptor assay, consistent with the follitropin bioactivity of the equine gonadotropin.", "contents": "Follitropin receptors in rat testis. Characterization with enzymatically 125I-labeled human follitropin. The interaction between enzymatically radioiodinated human follitropin and the follitropin receptors in testis homogenate was investigated in immature and adult rats. The 125I-labeled human follitropin exhibited high binding activity with specific binding of up to 17% in the presence of an excess of testis homogenate. Approx. 50% of the bound hormone could be eluted at pH 5, and the receptor purified tracer exhibited a 3.6-fold increase in binding activity when compared with the original tracer preparation. Quantitative analysis of equilibrium binding data was performed with corrections for the measured specific activity and maximum binding activity of the tracer hormone. The equilibrium association constants (Ka) determined 24 degrees C were not significantly different in immature and adult rat testis, and the mean value for Ka was 3.9 . 10(9) M-1. At 37 degrees C, the Ka value obtained using immature rat testis was 1.3 . 10(10) M-1. The association of 125I-labeled human follitropin with immature rat testis homogenate was time and temperature dependent. In the presence of an excess of unlabeled hormone, 30--60% of the preformed hormone . receptor complex was dissociated after 24 h incubation. A specific and sensitive radioligand-receptor assay for follitropin was developed using immature rat testis homogenate. The minimum detectable dose of purified human follitropin was 0.6 ng, and human urinary and pituitary follitropin, ovine follitropin and pregnant mare serum gonadotropin reacted in the assay with equivalent slopes. The potencies of highly purified pregnent mare serum gonadotropin and highly purified human  follitropin were similar in the radioligand-receptor assay, consistent with the follitropin bioactivity of the equine gonadotropin."}
{"id": "PMID:208642", "title": "Catabolite repression of isocitrate lyase in methylamine-grown Pseudomonas MA. Effect of carbon and nitrogen sources.", "content": "The synthesis of the C1-type isocitrate lyase found during growth of Pseudomonas MA on methylamine was investigated. It was shown that this enzyme is subject to catabolite repression by preferred carbon sources, e.g., succinate, and by ammonia. The carbon repression can be overcome by cyclic AMP, which was shown to be acting at the transcriptional level. Repression by ammonia is overcome during growth with methylamine as sole nitrogen, but not carbon, source. Uptake experiments showed that the uptake of methylamine from the medium was prevented by ammonia in the presence, but not in the absence, of an alternative carbon source. Measurement of cyclic AMP levels in cells grown on methylamine and on succinate, glycerol, glucose and acetate as carbon sources (with ammonium chloride as nitrogen source) revealed that methylamine-grown cells have the lowest cyclic AMP level despite having the highest C1-type isocitrate lyase activity. Cells grown on acetate with methylamine as sole nitrogen source possess both C1-type and C2-type isocitrate lyase. The results indicate that the synthesis of C1-isocitrate lyase is under control by repression-derepression involving a specific inducer, cyclic AMP, and an effector whose action is related to the nitrogen supply of the cell.", "contents": "Catabolite repression of isocitrate lyase in methylamine-grown Pseudomonas MA. Effect of carbon and nitrogen sources. The synthesis of the C1-type isocitrate lyase found during growth of Pseudomonas MA on methylamine was investigated. It was shown that this enzyme is subject to catabolite repression by preferred carbon sources, e.g., succinate, and by ammonia. The carbon repression can be overcome by cyclic AMP, which was shown to be acting at the transcriptional level. Repression by ammonia is overcome during growth with methylamine as sole nitrogen, but not carbon, source. Uptake experiments showed that the uptake of methylamine from the medium was prevented by ammonia in the presence, but not in the absence, of an alternative carbon source. Measurement of cyclic AMP levels in cells grown on methylamine and on succinate, glycerol, glucose and acetate as carbon sources (with ammonium chloride as nitrogen source) revealed that methylamine-grown cells have the lowest cyclic AMP level despite having the highest C1-type isocitrate lyase activity. Cells grown on acetate with methylamine as sole nitrogen source possess both C1-type and C2-type isocitrate lyase. The results indicate that the synthesis of C1-isocitrate lyase is under control by repression-derepression involving a specific inducer, cyclic AMP, and an effector whose action is related to the nitrogen supply of the cell."}
{"id": "PMID:208643", "title": "Hormone-specific responses and biosynthesis of sulfolipids in cell lines derived from mammalian kidney.", "content": "The established cell lines isolated from mammalian kidney were characterized by its receptor activities against hormones and the ability to synthesize sulfolipids localized in the renal tubule. The level of 3':5'-cyclic AMP in JTC-12.P3 (monkey kidney) cells increased in 2 min as much as 2.5-5-fold on activation with 1.0 unit/ml of bovine parathyroid hormone or 1.9 units/ml of synthetic parathyroid hormone (1-34) resulting in intracellular cyclic AMP concentration of more than 40 pmol/mg protein. Prostaglandin E1 (14 micronM) and isopropylnorepinephrine (10 micronM) were also found to increase the concentration of cyclic AMP by more than 30- and 9-fold, respectively. Addition in medium of calcitonin, arginine vasopressin, adrenocorticotropic hormone and glucagon caused no significant changes of cyclic AMP level in the cell. In contrast, MDCK, a cell line isolated from canine kidney, reacted to arginine vasopressin, isopropylnorepinephrine and prostaglandin E1 and only slightly to parathyroid hormone. MDBK cell line derived from bovine kidney or fibroblast cell lines from rat lung and guinea pig kidney did not react to any of the hormones specific to kidney, i.e. arginine vasopressin, calcitonin or parathyroid hormone in the presence of theophylline. However, in the presence of 2 mM isobutylmethylxanthine, small but significant elevation of cellular cyclic AMP levels in response to calcitonin, arginine vasopressin, isopropylnorepinephrine and prostaglandin E1 was observed. The cell lines JTC-12, MDCK and MDBK, when incubated with H235SO4, incorporated the isotope into sulfolipids assigned as sulfatides and ceramide dihexoside sulfate or in MDCK also into cholesterol sulfate. The results suggested that JTC-12, MDCK and MDBK cell lines are epithelial origin and also JTC-12 and MDCK originated most probably from renal tubular cells of cortex and medulla, respectively.", "contents": "Hormone-specific responses and biosynthesis of sulfolipids in cell lines derived from mammalian kidney. The established cell lines isolated from mammalian kidney were characterized by its receptor activities against hormones and the ability to synthesize sulfolipids localized in the renal tubule. The level of 3':5'-cyclic AMP in JTC-12.P3 (monkey kidney) cells increased in 2 min as much as 2.5-5-fold on activation with 1.0 unit/ml of bovine parathyroid hormone or 1.9 units/ml of synthetic parathyroid hormone (1-34) resulting in intracellular cyclic AMP concentration of more than 40 pmol/mg protein. Prostaglandin E1 (14 micronM) and isopropylnorepinephrine (10 micronM) were also found to increase the concentration of cyclic AMP by more than 30- and 9-fold, respectively. Addition in medium of calcitonin, arginine vasopressin, adrenocorticotropic hormone and glucagon caused no significant changes of cyclic AMP level in the cell. In contrast, MDCK, a cell line isolated from canine kidney, reacted to arginine vasopressin, isopropylnorepinephrine and prostaglandin E1 and only slightly to parathyroid hormone. MDBK cell line derived from bovine kidney or fibroblast cell lines from rat lung and guinea pig kidney did not react to any of the hormones specific to kidney, i.e. arginine vasopressin, calcitonin or parathyroid hormone in the presence of theophylline. However, in the presence of 2 mM isobutylmethylxanthine, small but significant elevation of cellular cyclic AMP levels in response to calcitonin, arginine vasopressin, isopropylnorepinephrine and prostaglandin E1 was observed. The cell lines JTC-12, MDCK and MDBK, when incubated with H235SO4, incorporated the isotope into sulfolipids assigned as sulfatides and ceramide dihexoside sulfate or in MDCK also into cholesterol sulfate. The results suggested that JTC-12, MDCK and MDBK cell lines are epithelial origin and also JTC-12 and MDCK originated most probably from renal tubular cells of cortex and medulla, respectively."}
{"id": "PMID:208644", "title": "Adrenocorticotropin-induced unresponsiveness in cultured adrenal tumor cells.", "content": "Our results demonstrate that adrenocorticotropin (ACTH)-induced refractoriness occurs in cultured adrenal tumor cells. Cells became 85% refractory to ACTH-induced cyclic AMP formation in 20 min and the effect persisted if the hormone remained in the incubation medium. Refractory cells gradually regained hormone-specific responsiveness within 24 h if cultures were incubated in fresh media containing serum. The observed effect is hormone specific since cyclic AMP could not induce unresponsiveness to ACTH. The addition of ACTH plus inhibitors of protein synthesis partially reversed hormone-specific refractoriness. However, preincubation with cycloheximide or diphtheria toxin led to superinduction of ACTH-induced cyclic AMP formation. These experiments suggest that unresponsiveness, following hormonal activation of adrenal cells, may be related to a decrease in hormone-specific binding sites or to synthesis of an adenylate cyclase inhibitor.", "contents": "Adrenocorticotropin-induced unresponsiveness in cultured adrenal tumor cells. Our results demonstrate that adrenocorticotropin (ACTH)-induced refractoriness occurs in cultured adrenal tumor cells. Cells became 85% refractory to ACTH-induced cyclic AMP formation in 20 min and the effect persisted if the hormone remained in the incubation medium. Refractory cells gradually regained hormone-specific responsiveness within 24 h if cultures were incubated in fresh media containing serum. The observed effect is hormone specific since cyclic AMP could not induce unresponsiveness to ACTH. The addition of ACTH plus inhibitors of protein synthesis partially reversed hormone-specific refractoriness. However, preincubation with cycloheximide or diphtheria toxin led to superinduction of ACTH-induced cyclic AMP formation. These experiments suggest that unresponsiveness, following hormonal activation of adrenal cells, may be related to a decrease in hormone-specific binding sites or to synthesis of an adenylate cyclase inhibitor."}
{"id": "PMID:208645", "title": "Identification of the regulatory steps in gluconeogenesis in cotyledons of Cucurbita pepo.", "content": "1. The aim of this work was to discover the steps at which the conversion of oxaloacetate to glucose 6-phosphate during gluconeogenesis is regulated in the cotyledons of 5-day-old seedlings of Cucurbita pepo. 2. We estimated the maximum catalytic activities of all the enzymes in the above sequence and also the amounts of their substrates present in vivo. The results show that the reactions catalysed by fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase are the only ones in the sequence that are substantially displaced from equilibrium in vivo. 3. We also determined the effects of 3-mercaptopicolinic acid, an inhibitor of gluconeogenesis, on the amounts of the gluconeogenic intermediates present in vivo. The results show that the enzyme system, fructose-1,6-bisphosphatase: phosphofructokinase, and the system phosphoenolpyruvate carboxykinase: phosphoenolpyruvate carboxylase make major contributions to the regulation of gluconeogenesis in the cotyledons. 4. Possible mechanisms for the above regulation are discussed.", "contents": "Identification of the regulatory steps in gluconeogenesis in cotyledons of Cucurbita pepo. 1. The aim of this work was to discover the steps at which the conversion of oxaloacetate to glucose 6-phosphate during gluconeogenesis is regulated in the cotyledons of 5-day-old seedlings of Cucurbita pepo. 2. We estimated the maximum catalytic activities of all the enzymes in the above sequence and also the amounts of their substrates present in vivo. The results show that the reactions catalysed by fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase are the only ones in the sequence that are substantially displaced from equilibrium in vivo. 3. We also determined the effects of 3-mercaptopicolinic acid, an inhibitor of gluconeogenesis, on the amounts of the gluconeogenic intermediates present in vivo. The results show that the enzyme system, fructose-1,6-bisphosphatase: phosphofructokinase, and the system phosphoenolpyruvate carboxykinase: phosphoenolpyruvate carboxylase make major contributions to the regulation of gluconeogenesis in the cotyledons. 4. Possible mechanisms for the above regulation are discussed."}
{"id": "PMID:208646", "title": "Azidophenantridinium compounds as photoaffinity labels of cholinergic proteins.", "content": "The synthesis of diazidopropidium and diazidoethidium is described. The applicability of these compounds as photoaffinity labels for cholinergic proteins has been investigated: diazidopropidium inhibits neuromuscular transmission. This inhibition is reversible if the compound is applied in the dark but becomes irreversible after irradiation with white light. Inhibition is accompanied by a disappearance of miniature endplate potentials. Electrophysiological analysis of this effect indicates that diazidopropidium acts postsynaptically by blocking the acetylcholine receptors. At the molecular level the action of diazidopropidium and diazidoethidium on acetylcholinesterase has been investigated: both compounds appear to bind to a peripheral acetylcholine binding site of this enzyme. Binding of 125I-labeled alpha-neurotoxin from Naja naja siamensis to purified membranes from Torpedo californica electric tissue rich in acetylcholine receptors is diminished after incubation and irradiation with diazidopropidium. About half of the toxin binding sites appear to be blocked by the photoaffinity label.", "contents": "Azidophenantridinium compounds as photoaffinity labels of cholinergic proteins. The synthesis of diazidopropidium and diazidoethidium is described. The applicability of these compounds as photoaffinity labels for cholinergic proteins has been investigated: diazidopropidium inhibits neuromuscular transmission. This inhibition is reversible if the compound is applied in the dark but becomes irreversible after irradiation with white light. Inhibition is accompanied by a disappearance of miniature endplate potentials. Electrophysiological analysis of this effect indicates that diazidopropidium acts postsynaptically by blocking the acetylcholine receptors. At the molecular level the action of diazidopropidium and diazidoethidium on acetylcholinesterase has been investigated: both compounds appear to bind to a peripheral acetylcholine binding site of this enzyme. Binding of 125I-labeled alpha-neurotoxin from Naja naja siamensis to purified membranes from Torpedo californica electric tissue rich in acetylcholine receptors is diminished after incubation and irradiation with diazidopropidium. About half of the toxin binding sites appear to be blocked by the photoaffinity label."}
{"id": "PMID:208647", "title": "Acidic-phosphoprotein phosphatase activity of rat ventral prostate nuclei: apparent lack of effect of androgens.", "content": "A protein phosphatase activity has been demonstrated in nuclei of rat ventral prostate utilizing 32P-labelled phosvitin as a model acidic phosphoprotein substrate. This phosphoprotein phosphatase has a pH optimum of 6.7, is unaffected by the sulphydryl protecting agent 2-mercaptoethanol, and requires a divalent cation for maximal activity. Of the various divalent cations tested, Mg2+ is the most effective in reactivating the EDTA-inhibited enzyme. The phosphatase is inhibited by sodium flouride, sodium oxalate, N-ethylmaleimide, ATP and ADP but is relatively insensitive to ammonium molybdate. Increased ionic strength of the reaction medium also causes a reduction in the enzyme activity, e.g., by 48% at 200 mM sodium chloride. The activity of the acidic phosphoprotein phosphatase did not change significantly at 48 h or 96 h post-orchiectomy when expressed per unit of nuclear protein. However, it is reduced by approx. 30% at these times after castration if based on DNA content. The decline in activity per nucleus reflects the decrease in the realtive nuclear protein content observed at 48 h or 96 h post-orchiectomy. This suggests that the decline in the phosphorylation of prostatic nuclear acidic proteins which occurs upon androgen withdrawal is not due to increased nuclear phosphatase activity.", "contents": "Acidic-phosphoprotein phosphatase activity of rat ventral prostate nuclei: apparent lack of effect of androgens. A protein phosphatase activity has been demonstrated in nuclei of rat ventral prostate utilizing 32P-labelled phosvitin as a model acidic phosphoprotein substrate. This phosphoprotein phosphatase has a pH optimum of 6.7, is unaffected by the sulphydryl protecting agent 2-mercaptoethanol, and requires a divalent cation for maximal activity. Of the various divalent cations tested, Mg2+ is the most effective in reactivating the EDTA-inhibited enzyme. The phosphatase is inhibited by sodium flouride, sodium oxalate, N-ethylmaleimide, ATP and ADP but is relatively insensitive to ammonium molybdate. Increased ionic strength of the reaction medium also causes a reduction in the enzyme activity, e.g., by 48% at 200 mM sodium chloride. The activity of the acidic phosphoprotein phosphatase did not change significantly at 48 h or 96 h post-orchiectomy when expressed per unit of nuclear protein. However, it is reduced by approx. 30% at these times after castration if based on DNA content. The decline in activity per nucleus reflects the decrease in the realtive nuclear protein content observed at 48 h or 96 h post-orchiectomy. This suggests that the decline in the phosphorylation of prostatic nuclear acidic proteins which occurs upon androgen withdrawal is not due to increased nuclear phosphatase activity."}
{"id": "PMID:208648", "title": "Comparison of large unilamellar vesicles prepared by a petroleum ether vaporization method with multilamellar vesicles: ESR, diffusion and entrapment analyses.", "content": "Large unilamellar vesicles, prepared by a petroleum ether vaporization method, were compared to multilamellar vesicles with respect to a number of physical and functional properties. Rotational correlation time approximations, derived from ESR spectra of both hydrophilic (3-doxyl cholestane) and hydrophobic (3-doxyl androstanol) steroid spin probes, indicated similar molecular packing of lipids in bilayers of multilamellar and large unilamellar liposomes. Light scattering measurements demonstrated a reduction in apparent absorbance of large unilamellar vesicles, suggesting loss of multilamellar structure which was confirmed by electron microscopy. Furthermore, large unilamellar vesicles exhibited enhanced passive diffusion rates of small solutes, releasing a greater percentage of their contents within 90 min than multilamellar vesicles, and reflecting the less restricted diffusion of a unilamellar system. The volume trapping capacity of large unilamellar vesicles far exceeded that of multilamellar liposomes, except in the presence of a trapped protein, soy bean trypsin inhibitor, which reduced the volume of the aqueous compartments of large unilamellar vesicles. Finally, measurement of vesicle diameters from electron micrographs of large unilamellar vesicles showed a vesicle size distribution predominantly in the range of 0.1--0.4 micron with a mean diameter of 0.21 micron.", "contents": "Comparison of large unilamellar vesicles prepared by a petroleum ether vaporization method with multilamellar vesicles: ESR, diffusion and entrapment analyses. Large unilamellar vesicles, prepared by a petroleum ether vaporization method, were compared to multilamellar vesicles with respect to a number of physical and functional properties. Rotational correlation time approximations, derived from ESR spectra of both hydrophilic (3-doxyl cholestane) and hydrophobic (3-doxyl androstanol) steroid spin probes, indicated similar molecular packing of lipids in bilayers of multilamellar and large unilamellar liposomes. Light scattering measurements demonstrated a reduction in apparent absorbance of large unilamellar vesicles, suggesting loss of multilamellar structure which was confirmed by electron microscopy. Furthermore, large unilamellar vesicles exhibited enhanced passive diffusion rates of small solutes, releasing a greater percentage of their contents within 90 min than multilamellar vesicles, and reflecting the less restricted diffusion of a unilamellar system. The volume trapping capacity of large unilamellar vesicles far exceeded that of multilamellar liposomes, except in the presence of a trapped protein, soy bean trypsin inhibitor, which reduced the volume of the aqueous compartments of large unilamellar vesicles. Finally, measurement of vesicle diameters from electron micrographs of large unilamellar vesicles showed a vesicle size distribution predominantly in the range of 0.1--0.4 micron with a mean diameter of 0.21 micron."}
{"id": "PMID:208649", "title": "Superoxide dismutase of the eye: relative functions of superoxide dismutase and catalase in protecting the ocular lens from oxidative damage.", "content": "1. Activities of superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1) have been estimated in eye tissues. In rabbit eye, superoxide dismutase is present in corneal epithelium, corneal endothelium, lens, iris, ciliary body and retina. In lens the activity is in capsule epithelium. 2. Copper chelator diethyldithiocarbamate inhibited lens superoxide dismutase in vitro and in vivo in rabbit. 3. H2O2 caused inhibition of superoxide dismutase activity of lens extract, and this inhibition was potentiated by the catalase inhibitor 3-amino-1H-1,2,4-triazole (3-aminotriazole) or NaN3. 3-Aminotriazole or NaN3 had no effect on lens superoxide dismutase. Thus endogenous catalase of lens affords protection to the lens superoxide dismutase from inactivation by H2O2. 4. In rabbit having early cataract (vacuolar stage) induced by feeding-3-aminotriazole, there was a decrease in superoxide dismutase of lens, a fall in ascorbic acid of ocular humors and lens, and a 2--3-Fold increase in H2O2 of aqueous humor and vitreous humor. We conclude that catalase of eye affords protection to the lens from H2O2 and it also protects superoxide dismutase of lens from inactivation by H2O2. Superoxide dismutase, in turn, protects the lens from the superoxide radical, O2.-. It is likely that inhibition of these enzymes may lead to production of the highly reactive oxidant, the hydroxyl radical, under pathological conditions when H2O2 concentration in vivo exceeds physiological limits as in cataract induced by 3-aminotriazole. A scheme of reaction mechanism has been proposed to explain the relative functions of ocular catalase and superoxide dismutase. Such a mechanism may be involved in cataractogenic process in the human.", "contents": "Superoxide dismutase of the eye: relative functions of superoxide dismutase and catalase in protecting the ocular lens from oxidative damage. 1. Activities of superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1) have been estimated in eye tissues. In rabbit eye, superoxide dismutase is present in corneal epithelium, corneal endothelium, lens, iris, ciliary body and retina. In lens the activity is in capsule epithelium. 2. Copper chelator diethyldithiocarbamate inhibited lens superoxide dismutase in vitro and in vivo in rabbit. 3. H2O2 caused inhibition of superoxide dismutase activity of lens extract, and this inhibition was potentiated by the catalase inhibitor 3-amino-1H-1,2,4-triazole (3-aminotriazole) or NaN3. 3-Aminotriazole or NaN3 had no effect on lens superoxide dismutase. Thus endogenous catalase of lens affords protection to the lens superoxide dismutase from inactivation by H2O2. 4. In rabbit having early cataract (vacuolar stage) induced by feeding-3-aminotriazole, there was a decrease in superoxide dismutase of lens, a fall in ascorbic acid of ocular humors and lens, and a 2--3-Fold increase in H2O2 of aqueous humor and vitreous humor. We conclude that catalase of eye affords protection to the lens from H2O2 and it also protects superoxide dismutase of lens from inactivation by H2O2. Superoxide dismutase, in turn, protects the lens from the superoxide radical, O2.-. It is likely that inhibition of these enzymes may lead to production of the highly reactive oxidant, the hydroxyl radical, under pathological conditions when H2O2 concentration in vivo exceeds physiological limits as in cataract induced by 3-aminotriazole. A scheme of reaction mechanism has been proposed to explain the relative functions of ocular catalase and superoxide dismutase. Such a mechanism may be involved in cataractogenic process in the human."}
{"id": "PMID:208650", "title": "alpha-Hydroxy-beta-keto-gamma-aminobutyric acid in human urine.", "content": "A new amino acid has been isolated from the normal human urine. The chemical structure of the amino acid was determined to be alpha-hydroxy-beta-keto-gamma-aminobutyric acid based on its physical properties involving NMR, infrared and mass spectra, as well as chemical degradation and synthesis. In six healthy adults the urinary contents of the new amino acid were 3.2--4.5 mumol/24 h.", "contents": "alpha-Hydroxy-beta-keto-gamma-aminobutyric acid in human urine. A new amino acid has been isolated from the normal human urine. The chemical structure of the amino acid was determined to be alpha-hydroxy-beta-keto-gamma-aminobutyric acid based on its physical properties involving NMR, infrared and mass spectra, as well as chemical degradation and synthesis. In six healthy adults the urinary contents of the new amino acid were 3.2--4.5 mumol/24 h."}
{"id": "PMID:208651", "title": "The role of calcium and cyclic adenosine 3',5'-monophosphate in the regulation of glycogen metabolism in phagocytozing human polymorphonuclear leukocytes.", "content": "Incubation of human polymorphonuclear leukocytes in a glucose-free Krebs-Ringer bicarbonate buffer for 2 h resulted in glycogen depletion, decreased phosphorylase activity and increased synthase-R activity. Addition of dialyzed latex particles to starved leukocytes revealed a very rapid ingestion rate (half-maximal ingestion within 30 s). This uptake is followed by glycogenolysis associated with an immediate two-fold increase in phosphorylase a activity and a synthase-R to -D conversion within 30 s. Furthermore, in rapid time-course experiments with phagocytozing cells we found that the concentration of cyclic AMP increased by 93% within 15 s and returned to baseline values at 1 min. In a medium without added calcium and with 1 mM ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid, phagocytosis was blocked, cyclic AMP formation decreased by 50% and phosphorylase activation was abolished, but the conversion of synthase-R to -D was preserved. Addition of calcium ions to cells suspended in a calcium-free buffer without added latex results in phosphorylase activation and glycogenolysis, but not in cyclic AMP increase or synthase-R to -D conversion. Measurements of 45Ca efflux during phagocytosis suggest an initial increase in cytosolic calcium obtained by a release of membrane-bound 45Ca. Activation of phosphorylase during phagocytosis is thus presumably due to an increase in cytosol Ca2+ and subsequent activation of phosphorylase kinase, and is independent of the simultaneous increase in concentration of cyclic AMP. Phosphorylation of synthase R to the D form does not depend on the presence of Ca2+ in the extracellular phase.", "contents": "The role of calcium and cyclic adenosine 3',5'-monophosphate in the regulation of glycogen metabolism in phagocytozing human polymorphonuclear leukocytes. Incubation of human polymorphonuclear leukocytes in a glucose-free Krebs-Ringer bicarbonate buffer for 2 h resulted in glycogen depletion, decreased phosphorylase activity and increased synthase-R activity. Addition of dialyzed latex particles to starved leukocytes revealed a very rapid ingestion rate (half-maximal ingestion within 30 s). This uptake is followed by glycogenolysis associated with an immediate two-fold increase in phosphorylase a activity and a synthase-R to -D conversion within 30 s. Furthermore, in rapid time-course experiments with phagocytozing cells we found that the concentration of cyclic AMP increased by 93% within 15 s and returned to baseline values at 1 min. In a medium without added calcium and with 1 mM ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid, phagocytosis was blocked, cyclic AMP formation decreased by 50% and phosphorylase activation was abolished, but the conversion of synthase-R to -D was preserved. Addition of calcium ions to cells suspended in a calcium-free buffer without added latex results in phosphorylase activation and glycogenolysis, but not in cyclic AMP increase or synthase-R to -D conversion. Measurements of 45Ca efflux during phagocytosis suggest an initial increase in cytosolic calcium obtained by a release of membrane-bound 45Ca. Activation of phosphorylase during phagocytosis is thus presumably due to an increase in cytosol Ca2+ and subsequent activation of phosphorylase kinase, and is independent of the simultaneous increase in concentration of cyclic AMP. Phosphorylation of synthase R to the D form does not depend on the presence of Ca2+ in the extracellular phase."}
{"id": "PMID:208652", "title": "[Low temperature reduction of cytochrome c complexes].", "content": "The absorption spectra of ferricytochrome c complexes with azide, imidazole and cyanide reduced by trapped electrons at the liquid nitrogen temperature were investigated. Differences have been found between the absorption spectra at T=77 degrees K of cytochrome c complexes reduced by radiation and the absorption spectrum of ferrocytochrome c. These differences are supposed to be due to the axial ligation of the Fe(II) by exogenous ligand. The temperature increase led to the removal of exogenous ligand from Fe(II).", "contents": "[Low temperature reduction of cytochrome c complexes]. The absorption spectra of ferricytochrome c complexes with azide, imidazole and cyanide reduced by trapped electrons at the liquid nitrogen temperature were investigated. Differences have been found between the absorption spectra at T=77 degrees K of cytochrome c complexes reduced by radiation and the absorption spectrum of ferrocytochrome c. These differences are supposed to be due to the axial ligation of the Fe(II) by exogenous ligand. The temperature increase led to the removal of exogenous ligand from Fe(II)."}
{"id": "PMID:208653", "title": "[Spin-label progesterone binding to serum albumin].", "content": "The binding of spin label progesterone to bovine serum albumin was studied by the spin-probe technique. The binding capacity of protein was established. It was shown that protein formed a rigid complex with steroid, the correlation time of this complex being 50 ns. In the complex the radical part of the steroidal molecule has a hydrophobic environment.", "contents": "[Spin-label progesterone binding to serum albumin]. The binding of spin label progesterone to bovine serum albumin was studied by the spin-probe technique. The binding capacity of protein was established. It was shown that protein formed a rigid complex with steroid, the correlation time of this complex being 50 ns. In the complex the radical part of the steroidal molecule has a hydrophobic environment."}
{"id": "PMID:208654", "title": "[Effect of ferricyanide, dark adaptation and aging on the properties of the EPR I signal of chloroplasts].", "content": "Ferricyanide (10-3 M) is shown to oxidize from 25 to 50% of the total P700 pool in the dark. The ferri-ferrocyanide mixture thus obtained, acting as redox buffer, accelerates the P700+ dark reduction after continuous far red illumination is turned off or after a saturating flash. The oxidized P700 yield on the flash increase in the presence of ferricyanide as a result oxidation of species in the neighborhood of P700 centers. During aging (24 h at 2--3 degrees in the dark) the yield of flash-induced P700 oxidation also increases thus indicating the loss of cyclic electron flow in aged chloroplasts.", "contents": "[Effect of ferricyanide, dark adaptation and aging on the properties of the EPR I signal of chloroplasts]. Ferricyanide (10-3 M) is shown to oxidize from 25 to 50% of the total P700 pool in the dark. The ferri-ferrocyanide mixture thus obtained, acting as redox buffer, accelerates the P700+ dark reduction after continuous far red illumination is turned off or after a saturating flash. The oxidized P700 yield on the flash increase in the presence of ferricyanide as a result oxidation of species in the neighborhood of P700 centers. During aging (24 h at 2--3 degrees in the dark) the yield of flash-induced P700 oxidation also increases thus indicating the loss of cyclic electron flow in aged chloroplasts."}
{"id": "PMID:208655", "title": "[Limiting behavior of a model of the impulse activity of a neuron for large frequency of input flow and small contributions of a single synapse (non-diffusion approximation)].", "content": "The limit behavior of probability models of neuron's firing, viz. models with exponential decay and constant threshold is considered. These models differ from each other by F(v), distribution of jumps of potential after arrival of input impulse. If average number of input impulses arriving during the decaying time of one impulse in very large and threshold depolarisation, measured by unit of average jump of potential, is large too, than limit density of interspike interval distribution does not depend on form of F(v); and depends on other neuron's parameters mean and variance of F(v). Moreover, the form of this density depends on only one parameter--normalised threshold. Under this condition interspike interval distribution for diffusion model converges to the same limit. Lapase transform for limit distribution is found and results of its numeric inverts are given.", "contents": "[Limiting behavior of a model of the impulse activity of a neuron for large frequency of input flow and small contributions of a single synapse (non-diffusion approximation)]. The limit behavior of probability models of neuron's firing, viz. models with exponential decay and constant threshold is considered. These models differ from each other by F(v), distribution of jumps of potential after arrival of input impulse. If average number of input impulses arriving during the decaying time of one impulse in very large and threshold depolarisation, measured by unit of average jump of potential, is large too, than limit density of interspike interval distribution does not depend on form of F(v); and depends on other neuron's parameters mean and variance of F(v). Moreover, the form of this density depends on only one parameter--normalised threshold. Under this condition interspike interval distribution for diffusion model converges to the same limit. Lapase transform for limit distribution is found and results of its numeric inverts are given."}
{"id": "PMID:208659", "title": "Relationships in hydrogen metabolism between hydrogenase and nitrogenase in phototrophic bacteria.", "content": "Purple bacteria Rhodospirillum rubrum and Thiocapsa roseopersicina form two enzymes, hydrogenase and nitrogenase, which participate in hydrogen metabolism. H2 photoproduction in these bacteria is associated mainly or completely with the action of nitrogenase. The soluble and membrane-bound hydrogenases of T. roseopersicina have similar physicochemical properties (mol. weight, subunit composition, N-terminal amino acids, Fe2+ and S2- content, pl. Eo'). In comparison with other hydrogenases the enzyme from R. rubrum and T. roseopersicina evolve H2 with high rate from reduced cytochrome c3, but not from ferredoxins. H2 production and N2 fixation take place in the presence of NAD(P)H. NADP-reductase, ferredoxin and cytochrome c3 participate in this reaction. Possible relationships between hydrogenase-nitrogenase in the metabolism of molecular hydrogen are discussed.", "contents": "Relationships in hydrogen metabolism between hydrogenase and nitrogenase in phototrophic bacteria. Purple bacteria Rhodospirillum rubrum and Thiocapsa roseopersicina form two enzymes, hydrogenase and nitrogenase, which participate in hydrogen metabolism. H2 photoproduction in these bacteria is associated mainly or completely with the action of nitrogenase. The soluble and membrane-bound hydrogenases of T. roseopersicina have similar physicochemical properties (mol. weight, subunit composition, N-terminal amino acids, Fe2+ and S2- content, pl. Eo'). In comparison with other hydrogenases the enzyme from R. rubrum and T. roseopersicina evolve H2 with high rate from reduced cytochrome c3, but not from ferredoxins. H2 production and N2 fixation take place in the presence of NAD(P)H. NADP-reductase, ferredoxin and cytochrome c3 participate in this reaction. Possible relationships between hydrogenase-nitrogenase in the metabolism of molecular hydrogen are discussed."}
{"id": "PMID:208660", "title": "EPR determination of the oxidation-reduction potentials of the hemes in cytochrome c3 from Desulfovibrio vulgaris.", "content": "EPR spectroscopy in conjunction with oxidation-reduction potentiometry has been used to determine the half-reduction potentials of the four hemes of cytochrome c3. As predicted, the four hemes of cytochrome c3 have different mid-point potentials. The Em values are: Heme I,--284 mV; Heme II,--310 mV; Heme III,--324 mV and Heme IV,--319 mV. The n-values in each case was near one.", "contents": "EPR determination of the oxidation-reduction potentials of the hemes in cytochrome c3 from Desulfovibrio vulgaris. EPR spectroscopy in conjunction with oxidation-reduction potentiometry has been used to determine the half-reduction potentials of the four hemes of cytochrome c3. As predicted, the four hemes of cytochrome c3 have different mid-point potentials. The Em values are: Heme I,--284 mV; Heme II,--310 mV; Heme III,--324 mV and Heme IV,--319 mV. The n-values in each case was near one."}
{"id": "PMID:208656", "title": "[Spike transmission in statistical neuronal ensembles. IVa. Stating the problem in a diffusion approximation].", "content": "An area of tissue in the field CA3 of the Hippocampus has been selected controled by a basket cell. The functioning of the basket cell has been described by a point approximation method forthe transport equation, and that of the ensemble of pyramidal cells by a diffusion approximation one. Furthermore, the area of tissue is broken up into N2 of \"cells\" wherein a transition is effected from the diffusion equation of the N2 of the point equations involved. If the sizes of \"cells\" are commeasurable to the diffusional length of the pyramidal cell collaterals each \"cells\" being relatively independent generator of activity. In the latter case the fundamental interaction type is the mutual negative influence of the \"cells\" through the basket cell. Should the area be broken up into further, the mutual influence of the \"cells\" becomes noticeable and cannot be neglected. The behaviour of spatially homogenous diffusion approximation model is equivalent of the point approximation model.", "contents": "[Spike transmission in statistical neuronal ensembles. IVa. Stating the problem in a diffusion approximation]. An area of tissue in the field CA3 of the Hippocampus has been selected controled by a basket cell. The functioning of the basket cell has been described by a point approximation method forthe transport equation, and that of the ensemble of pyramidal cells by a diffusion approximation one. Furthermore, the area of tissue is broken up into N2 of \"cells\" wherein a transition is effected from the diffusion equation of the N2 of the point equations involved. If the sizes of \"cells\" are commeasurable to the diffusional length of the pyramidal cell collaterals each \"cells\" being relatively independent generator of activity. In the latter case the fundamental interaction type is the mutual negative influence of the \"cells\" through the basket cell. Should the area be broken up into further, the mutual influence of the \"cells\" becomes noticeable and cannot be neglected. The behaviour of spatially homogenous diffusion approximation model is equivalent of the point approximation model."}
{"id": "PMID:208661", "title": "NMR studies of electron carrier proteins from sulphate reducing bacteria.", "content": "The sulphate-reducing bacteria have a complex electron transfer system which leads to the reduction of sulphate by oxidation of either organic substrates or molecular hydrogen. These bacteria can either produce or consume molecular hydrogen. The central part of this electron pathway for Desulovibrio gigas is constituted by hydrogenase (3 X (4Fe-4S)). cytochrome c3 (4 haems with different redox potentials) and a one (4Fe-4S) cluster ferredoxin. This ferredoxin is isolated in different oligomeric forms, which stabilize different oxidation states and have different physiological roles; the trimer FdI being involved in the production of H2 and the tetramer FdII being more efficient for the consumption of H2. The presence of intrinsic probes (the iron ions) in these proteins is particularly helpful for structural studies using NMR spectroscopy. These studies allowed a characterization of the oxidation states used by the different oligomers of the ferredoxin and obtaintion of structural information on multi-haem cytochromes (c3 and c7). NMR is also suitable to study protein-protein interaction. The study of the complex formed between FdII and cytochrome c3 has shown that there is an alteration of the kinetics of electron transfer upon complexation.", "contents": "NMR studies of electron carrier proteins from sulphate reducing bacteria. The sulphate-reducing bacteria have a complex electron transfer system which leads to the reduction of sulphate by oxidation of either organic substrates or molecular hydrogen. These bacteria can either produce or consume molecular hydrogen. The central part of this electron pathway for Desulovibrio gigas is constituted by hydrogenase (3 X (4Fe-4S)). cytochrome c3 (4 haems with different redox potentials) and a one (4Fe-4S) cluster ferredoxin. This ferredoxin is isolated in different oligomeric forms, which stabilize different oxidation states and have different physiological roles; the trimer FdI being involved in the production of H2 and the tetramer FdII being more efficient for the consumption of H2. The presence of intrinsic probes (the iron ions) in these proteins is particularly helpful for structural studies using NMR spectroscopy. These studies allowed a characterization of the oxidation states used by the different oligomers of the ferredoxin and obtaintion of structural information on multi-haem cytochromes (c3 and c7). NMR is also suitable to study protein-protein interaction. The study of the complex formed between FdII and cytochrome c3 has shown that there is an alteration of the kinetics of electron transfer upon complexation."}
{"id": "PMID:208662", "title": "[Anion-sensitive adenosine triphosphatase from membranes of rat red blood cells].", "content": "Anion-sensitive ATPase was solubilized from membranes to rat red blood cells. The effect of bicarhonate, sulfite and perchlorate on the activity of ATPase was studied. Close resemblance of the properties of ATPase of rat red blood cells and of mitochondrial ATPase was observed.", "contents": "[Anion-sensitive adenosine triphosphatase from membranes of rat red blood cells]. Anion-sensitive ATPase was solubilized from membranes to rat red blood cells. The effect of bicarhonate, sulfite and perchlorate on the activity of ATPase was studied. Close resemblance of the properties of ATPase of rat red blood cells and of mitochondrial ATPase was observed."}
{"id": "PMID:208657", "title": "[Study of the reaction between steroids and serum albumin by the spin probe method].", "content": "The data obtained from the study of interaction of two steroids with serum albumin shows that D-ring of steroid molecule has more hidrophobic environment then A-ring in the complexes of steroid with protein. The plane of steroid is perpendicular to the long axis of protein molecule.", "contents": "[Study of the reaction between steroids and serum albumin by the spin probe method]. The data obtained from the study of interaction of two steroids with serum albumin shows that D-ring of steroid molecule has more hidrophobic environment then A-ring in the complexes of steroid with protein. The plane of steroid is perpendicular to the long axis of protein molecule."}
{"id": "PMID:208663", "title": "[Allosteric regulation of ceruloplasmin activity].", "content": "Study of the interactions of homogenous human ceruloplasmin preparations with histamine show that the rate of p-phenylene diamine oxidation by ceruloplasmin is increased in the presence of histamine; the increase in the enzyme activity is independent of histamine concentration. The dependence of the reaction rate on substrate concentration is S-shaped, both in the presence and in the absence of histamine. The respective values of the Hill coefficient and Rs for the enzyme in the presence and in the absence of histamine are 2.5 and 2.0 and 8.0 and 10.4. Histamine does not change ceruloplasmin-specific absorption at 610 nm. Evidence from EPR studies show that histamine does not interact with Cu of the enzyme active center. During interaction with histamine the antigenic properties of the enzyme are changed. Histamine increases the oxidase activity of the enzyme in human and rat blood sera and exerts multifold effects on the enzyme activity in patients with hepatolenticular degeneration. After injection of histamine to rats the enzyme activity is increased without a simultaneous increase in Cu concentration in the blood serum, i.e. without de novo synthesis of ceruloplasmin. The data obtained suggest that ceruloplasmin is probably an allosteric enzyme, which histamine is its positive allosteric effector.", "contents": "[Allosteric regulation of ceruloplasmin activity]. Study of the interactions of homogenous human ceruloplasmin preparations with histamine show that the rate of p-phenylene diamine oxidation by ceruloplasmin is increased in the presence of histamine; the increase in the enzyme activity is independent of histamine concentration. The dependence of the reaction rate on substrate concentration is S-shaped, both in the presence and in the absence of histamine. The respective values of the Hill coefficient and Rs for the enzyme in the presence and in the absence of histamine are 2.5 and 2.0 and 8.0 and 10.4. Histamine does not change ceruloplasmin-specific absorption at 610 nm. Evidence from EPR studies show that histamine does not interact with Cu of the enzyme active center. During interaction with histamine the antigenic properties of the enzyme are changed. Histamine increases the oxidase activity of the enzyme in human and rat blood sera and exerts multifold effects on the enzyme activity in patients with hepatolenticular degeneration. After injection of histamine to rats the enzyme activity is increased without a simultaneous increase in Cu concentration in the blood serum, i.e. without de novo synthesis of ceruloplasmin. The data obtained suggest that ceruloplasmin is probably an allosteric enzyme, which histamine is its positive allosteric effector."}
{"id": "PMID:208665", "title": "A new animal model for schizophrenia: interactions with adrenergic mechanisms.", "content": "Amphetamine-induced stereotyped behavior in animals is proposed as a model for schizophrenia. Chronic amphetamine administration produces stereotyped behavior and a paranoid schizophreniform syndrome in man, whereas in animals a behavioral sensitization to stereotypy is evoked. We now show that phenylethylamine (PEA), an amphetamine-like stimulant concentrated in the limbic system of human brain, produces stereotypy in rats with a behavioral sensitization when chronically administered. In comparing amphetamine-induced stereotypy with PEA-induced stereotypy, we found that the alpha-adrenergic blocking agents phentolamine and phenoxybenzamine selectively antagonize PEA stereotypy, whereas the beta-adrenergic blocking agent propranolol fails to alter significantly stereotypies evoked by PEA or amphetamine administration. Catecholamine depletion by alpha-methyl-p-tyrosine administration blocks stereotypies induced by both PEA amphetamine, whereas selective norepinephrine depletion antagonizes only PEA stereotypy; the amino acid precursors of both norepinephrine and dopamine potentiate stereotypies. Therefore, PEA-elicited stereotypy, but not amphetamine-elicited stereotypy, is dependent upon norepinephrine; the significance of this for the PEA animal model of schizophrenia is discussed.", "contents": "A new animal model for schizophrenia: interactions with adrenergic mechanisms. Amphetamine-induced stereotyped behavior in animals is proposed as a model for schizophrenia. Chronic amphetamine administration produces stereotyped behavior and a paranoid schizophreniform syndrome in man, whereas in animals a behavioral sensitization to stereotypy is evoked. We now show that phenylethylamine (PEA), an amphetamine-like stimulant concentrated in the limbic system of human brain, produces stereotypy in rats with a behavioral sensitization when chronically administered. In comparing amphetamine-induced stereotypy with PEA-induced stereotypy, we found that the alpha-adrenergic blocking agents phentolamine and phenoxybenzamine selectively antagonize PEA stereotypy, whereas the beta-adrenergic blocking agent propranolol fails to alter significantly stereotypies evoked by PEA or amphetamine administration. Catecholamine depletion by alpha-methyl-p-tyrosine administration blocks stereotypies induced by both PEA amphetamine, whereas selective norepinephrine depletion antagonizes only PEA stereotypy; the amino acid precursors of both norepinephrine and dopamine potentiate stereotypies. Therefore, PEA-elicited stereotypy, but not amphetamine-elicited stereotypy, is dependent upon norepinephrine; the significance of this for the PEA animal model of schizophrenia is discussed."}
{"id": "PMID:208666", "title": "Spatially rearranged vision and REM sleep: a lack of effect.", "content": "An observation first made in our laboratory was responsible for focusing our attention upon an apparent increase in REM sleep in relation to altered visual experiences during the day. This finding was consistent with certain information-processing theories of REM sleep function and seemed to offer experimental support for them. Therefore, we proceeded to conduct a series of closely related experiments, designed to investigate further the possible REM-augmenting effects of spatially rearranged vision. Although our first two experiments seemed to support the original observation, subsequent, more carefully designed experiments, did not. The combined results from all of our experiments forced us to conclude that there is no consistent effect of distorted daytime vision on the amount or percentage of REM sleep. REM latency, or the number of rapid eye movements during REM periods. We suggest that future research on the topic employ experiments specifically designed to explore relationships between personality variables and a subject's REM sleep response to altered sensory input.", "contents": "Spatially rearranged vision and REM sleep: a lack of effect. An observation first made in our laboratory was responsible for focusing our attention upon an apparent increase in REM sleep in relation to altered visual experiences during the day. This finding was consistent with certain information-processing theories of REM sleep function and seemed to offer experimental support for them. Therefore, we proceeded to conduct a series of closely related experiments, designed to investigate further the possible REM-augmenting effects of spatially rearranged vision. Although our first two experiments seemed to support the original observation, subsequent, more carefully designed experiments, did not. The combined results from all of our experiments forced us to conclude that there is no consistent effect of distorted daytime vision on the amount or percentage of REM sleep. REM latency, or the number of rapid eye movements during REM periods. We suggest that future research on the topic employ experiments specifically designed to explore relationships between personality variables and a subject's REM sleep response to altered sensory input."}
{"id": "PMID:208676", "title": "Renal transplantation and viral infections. III. Clinical and virological correlations.", "content": "Studies of the serological development after 26 renal transplants confirm the high frequency of antibody rises not only against the herpes virus group, but also against other virus groups such as measles, Coxsackie B viruses. These antibody rises correlate with febrile episodes and hepatic dysfunction in which CMV is the most often involved. However, the frequency of antibody rises against various viral antigens without any clinical event to suggest viral etiology; the lack of concomitant virus isolation (except the herpes group), as well as the ocurrence of simultaneous antibody rises against several viruses, all suggest that some of these various antibody rises observed may be related to immunological dysfunction rather than to virus infection.", "contents": "Renal transplantation and viral infections. III. Clinical and virological correlations. Studies of the serological development after 26 renal transplants confirm the high frequency of antibody rises not only against the herpes virus group, but also against other virus groups such as measles, Coxsackie B viruses. These antibody rises correlate with febrile episodes and hepatic dysfunction in which CMV is the most often involved. However, the frequency of antibody rises against various viral antigens without any clinical event to suggest viral etiology; the lack of concomitant virus isolation (except the herpes group), as well as the ocurrence of simultaneous antibody rises against several viruses, all suggest that some of these various antibody rises observed may be related to immunological dysfunction rather than to virus infection."}
{"id": "PMID:208677", "title": "Abnormal lipoproteins in a case of primary biliary cirrhosis.", "content": "The serum of a patient diagnosed as a primary biliary cirrhosis was studied during the various evolutive stages of the disease. During the non-icteric period, the serum lipoprotein had the chemical composition (rich in cholesterol and phospholipids) of that found in cholestasis; however the bilirubinemia was normal, and no LPX was detected; there was a normal esterified to total cholesterol ratio and the alphaLP had not decreased, as expected, but increased and was divided into two fractions; immunoelectrophoretic studies of ultracentrifugal fractions showed some LP with HDL immunological properties, but with lower densities than that of normal HDL. We suggest that the phospholipid overloading of some of these HDL in the patient's serum could explain the changes in density. Some months after this study, the patient's serum exhibited the characteristics found in cholestasis, with disappearance of HDL and appearance of LPX. During the subsequent period, the serum again contained phospholipid rich HDL and LPX. In fact several LPX with different densities were found. It seems, therefore, that in cholestasis, LP undergo modification in which the HDL peptide chains play an important role.", "contents": "Abnormal lipoproteins in a case of primary biliary cirrhosis. The serum of a patient diagnosed as a primary biliary cirrhosis was studied during the various evolutive stages of the disease. During the non-icteric period, the serum lipoprotein had the chemical composition (rich in cholesterol and phospholipids) of that found in cholestasis; however the bilirubinemia was normal, and no LPX was detected; there was a normal esterified to total cholesterol ratio and the alphaLP had not decreased, as expected, but increased and was divided into two fractions; immunoelectrophoretic studies of ultracentrifugal fractions showed some LP with HDL immunological properties, but with lower densities than that of normal HDL. We suggest that the phospholipid overloading of some of these HDL in the patient's serum could explain the changes in density. Some months after this study, the patient's serum exhibited the characteristics found in cholestasis, with disappearance of HDL and appearance of LPX. During the subsequent period, the serum again contained phospholipid rich HDL and LPX. In fact several LPX with different densities were found. It seems, therefore, that in cholestasis, LP undergo modification in which the HDL peptide chains play an important role."}
{"id": "PMID:208672", "title": "Alteration of cellular ribonucleases associated with murine oncogenic virus infection.", "content": "The ribonuclease activity of peripheral lymphocytes from Balb/c mice  was studied at various intervals subsequent to infection of mice by oncornavirus. Lymphocytes from mice infected with Friend leukemia virus possessed elevation of RNase activity within 8 days subsequent to infection. Balb/c mice infected with Moloney sarcoma virus demonstrated an analogous elevation of RNase activity with 7-9 days postinfection. Diminishment of cellular RNase activity occurred in the Friend leukemia model concomitant to the occurrence of significant numbers of erythroblasts in the peripheral blood, while ribonuclease activity in lymphocytes from mice infected with Molney sarcoma virus returned to normal 1-2 weeks subsequent to host rejection of tumor. It is concluded that elevation of RNase activity within the lymphocyte represents an early event in oncogenic viral infection within these two tumor models. The possible meaning of elevation of RNase activity is a target (the lymphocyte) not predestined to undergo neoplastic transformation is discussed.", "contents": "Alteration of cellular ribonucleases associated with murine oncogenic virus infection. The ribonuclease activity of peripheral lymphocytes from Balb/c mice  was studied at various intervals subsequent to infection of mice by oncornavirus. Lymphocytes from mice infected with Friend leukemia virus possessed elevation of RNase activity within 8 days subsequent to infection. Balb/c mice infected with Moloney sarcoma virus demonstrated an analogous elevation of RNase activity with 7-9 days postinfection. Diminishment of cellular RNase activity occurred in the Friend leukemia model concomitant to the occurrence of significant numbers of erythroblasts in the peripheral blood, while ribonuclease activity in lymphocytes from mice infected with Molney sarcoma virus returned to normal 1-2 weeks subsequent to host rejection of tumor. It is concluded that elevation of RNase activity within the lymphocyte represents an early event in oncogenic viral infection within these two tumor models. The possible meaning of elevation of RNase activity is a target (the lymphocyte) not predestined to undergo neoplastic transformation is discussed."}
{"id": "PMID:208678", "title": "Experimental infection of Callithrix Jacchus marmosets with Herpesvirus ateles, Herpesvirus saimiri, and Epstein Barr virus.", "content": "We inoculated common marmosets (Callithrix Jacchus) with Herpesvirus ateles (HVA), Herpesvirus saimiri (HVS), and Epstein-Barr virus (EBV). HVA-induced tumors contained several cell types, including giant cells reminiscent of the Sternberg-Reed cells observed in human Hodgkin's disease. HVS and EBV did not induce tumors, although HVS was present in lymphocytes and elicited a strong antibody response. EBV elicited only a variable antibody response. We feel that more common marmosets should be used to determine if the pathologic and immunologic lesions caused by HVA would be a suitable animal model for Hodgkin's disease and/or other malignant lymphomas of man. Inconsistency in the induction of tumors by EBV and HVS in common marmosets suggets that this species may be a different type of model for human cancer research than the cottontop marmoset, which is the most susceptible animal host for EBV and HVS oncogenesis.", "contents": "Experimental infection of Callithrix Jacchus marmosets with Herpesvirus ateles, Herpesvirus saimiri, and Epstein Barr virus. We inoculated common marmosets (Callithrix Jacchus) with Herpesvirus ateles (HVA), Herpesvirus saimiri (HVS), and Epstein-Barr virus (EBV). HVA-induced tumors contained several cell types, including giant cells reminiscent of the Sternberg-Reed cells observed in human Hodgkin's disease. HVS and EBV did not induce tumors, although HVS was present in lymphocytes and elicited a strong antibody response. EBV elicited only a variable antibody response. We feel that more common marmosets should be used to determine if the pathologic and immunologic lesions caused by HVA would be a suitable animal model for Hodgkin's disease and/or other malignant lymphomas of man. Inconsistency in the induction of tumors by EBV and HVS in common marmosets suggets that this species may be a different type of model for human cancer research than the cottontop marmoset, which is the most susceptible animal host for EBV and HVS oncogenesis."}
{"id": "PMID:208674", "title": "Microtubules, cyclic AMP and lysosomal enzyme release. A review.", "content": "The importance of microtubules and cyclic AMP in the control of lysosomal enzyme release from polymorphonuclear leukocytes is questioned. The article is a short review of pertinent literature designed to stimulate further research into this important mechanism of inflammation.", "contents": "Microtubules, cyclic AMP and lysosomal enzyme release. A review. The importance of microtubules and cyclic AMP in the control of lysosomal enzyme release from polymorphonuclear leukocytes is questioned. The article is a short review of pertinent literature designed to stimulate further research into this important mechanism of inflammation."}
{"id": "PMID:208675", "title": "The Epstein-Barr virus (EBV) in human pathology. II. Serologic profiles of EBV infections.", "content": "Antibodies to EBV induced intracellular antigens, (VCA, EA, NA) and VCA-IgM antibodies have been investigated to define EBV serologic profile of 245 individuals. This profile was a first studied in EBV primary infections. In infectious mononucleosis, the efficiency of EBV serodiagnosis is lower than Paul Bunnel Davidsohn reaction (PBD) : primary infection profile is only characterised in 80% of the positive PBD infectious mononucleosis (IM). On the other hand, EBV antibodies are preponderant for diagnosis in other clinical manifestations of EBV primary-infection were PBD is not alwasy positive (47%). EBV antibodies of patients with various diseases and antibodies of normal subjects show different profiles. By interpretation of these profiles one discuss the possibility to characterize reinfection, and either latent or active persistant infection.", "contents": "The Epstein-Barr virus (EBV) in human pathology. II. Serologic profiles of EBV infections. Antibodies to EBV induced intracellular antigens, (VCA, EA, NA) and VCA-IgM antibodies have been investigated to define EBV serologic profile of 245 individuals. This profile was a first studied in EBV primary infections. In infectious mononucleosis, the efficiency of EBV serodiagnosis is lower than Paul Bunnel Davidsohn reaction (PBD) : primary infection profile is only characterised in 80% of the positive PBD infectious mononucleosis (IM). On the other hand, EBV antibodies are preponderant for diagnosis in other clinical manifestations of EBV primary-infection were PBD is not alwasy positive (47%). EBV antibodies of patients with various diseases and antibodies of normal subjects show different profiles. By interpretation of these profiles one discuss the possibility to characterize reinfection, and either latent or active persistant infection."}
{"id": "PMID:208679", "title": "The relationship of post-stimulus time and interval histograms to the timing characteristics of spike trains.", "content": "PST (post-stimulus time) and interval histograms computed from recorded spike trains are related to an average timing characteristics of the spike train. The exact nature of this relationship varies with recording parameters, interfering signals, the histogram bin width, and the duration of the measurement interval. This work describes the conditions under which a PST histogram can serve as an unbiased estimate of the ensemble average of a spike train's intensity and an interval histogram can serve as an unbiased estimate of the probability density function of the interspike intervals. Simulation studies are used to confirm the validity of the theoretical results. As an example of an application, these results are used to analyze recordings of singleunit activity in the eight cranial nerve.", "contents": "The relationship of post-stimulus time and interval histograms to the timing characteristics of spike trains. PST (post-stimulus time) and interval histograms computed from recorded spike trains are related to an average timing characteristics of the spike train. The exact nature of this relationship varies with recording parameters, interfering signals, the histogram bin width, and the duration of the measurement interval. This work describes the conditions under which a PST histogram can serve as an unbiased estimate of the ensemble average of a spike train's intensity and an interval histogram can serve as an unbiased estimate of the probability density function of the interspike intervals. Simulation studies are used to confirm the validity of the theoretical results. As an example of an application, these results are used to analyze recordings of singleunit activity in the eight cranial nerve."}
{"id": "PMID:208680", "title": "[Cyclic AMP activation of respiration of the liver mitochondria in different metabolic states].", "content": "cAMP 10(-6) activates the liver mitochondria respiration in all the metabolic states and failed to change or increased the phosphorylation rate in the oxidation of saturating concentration of succinate and isocitrate. Preincubation of mitochondria or homogenate of the liver with cAMP is obligatory for this effect. The fraction V of serum albumin and EDTA did not prevent the effect. Noradrenaline enhanced the mitochondrial respiration only in incubation with the homogenate. The effect of noradrenaline and cAMP was not summed up. Probably the noradrenaline effect was mediated through cAMP. The data obtained are against the decisive role of the respiration and phosphorylation uncoupling or the oxidation substrate accumulation and lead to the assumption on the mitochondria enzymes activation.", "contents": "[Cyclic AMP activation of respiration of the liver mitochondria in different metabolic states]. cAMP 10(-6) activates the liver mitochondria respiration in all the metabolic states and failed to change or increased the phosphorylation rate in the oxidation of saturating concentration of succinate and isocitrate. Preincubation of mitochondria or homogenate of the liver with cAMP is obligatory for this effect. The fraction V of serum albumin and EDTA did not prevent the effect. Noradrenaline enhanced the mitochondrial respiration only in incubation with the homogenate. The effect of noradrenaline and cAMP was not summed up. Probably the noradrenaline effect was mediated through cAMP. The data obtained are against the decisive role of the respiration and phosphorylation uncoupling or the oxidation substrate accumulation and lead to the assumption on the mitochondria enzymes activation."}
{"id": "PMID:208681", "title": "[Complementary RNA in the chicken sarcoma cells and Rous sarcoma virus].", "content": "The subcellular localization in chicken Rous sarcoma of nucleotide sequence, complementary to Rous sarcoma virus RNA was examined by RNA/RNA molecular hybridization. The preparations of radioiodinated virion RNA were annealed with RNAs from different fractions (nuclei, mitochondria, free and membrane-bound polyribosomes) isolated from chicken Rous sarcoma. Formation of RNA-ase resistant hybrids between the viral 125I-RNA and RNA from the mitochondria and membrane-bound polyribosomes was revealed. The latter were characterized by a higher relative redundancy of nucleotide sequences complementary to virion RNA than that in the former, by factor 446. The role of complementary ribonucleotide sequences is discussed.", "contents": "[Complementary RNA in the chicken sarcoma cells and Rous sarcoma virus]. The subcellular localization in chicken Rous sarcoma of nucleotide sequence, complementary to Rous sarcoma virus RNA was examined by RNA/RNA molecular hybridization. The preparations of radioiodinated virion RNA were annealed with RNAs from different fractions (nuclei, mitochondria, free and membrane-bound polyribosomes) isolated from chicken Rous sarcoma. Formation of RNA-ase resistant hybrids between the viral 125I-RNA and RNA from the mitochondria and membrane-bound polyribosomes was revealed. The latter were characterized by a higher relative redundancy of nucleotide sequences complementary to virion RNA than that in the former, by factor 446. The role of complementary ribonucleotide sequences is discussed."}
{"id": "PMID:208682", "title": "[Hematopoietic tissue reactions associated with the growth of syngeneic transplanted tumors in mice].", "content": "Hemangiopericytoma growth in syngeneic male mice F1 (CBA X C57BL/bj) led to regular hemopoietic changes: an increase in the spleen weight, spleen cell count, in the number of colony-forming units (CFU). It also induced augmentation of myelopoiesis in the spleen and leukocytosis with a sharp increase of segmented granulocytes in the circulating blood characterized as the \"leukemoid reaction\" syndrome. The latter occurred even when the tumour cells were transplanted into the splenectomized host. Although less marked, this leukemoid reaction was also noted in advanced hepatoma transplanted to syngeneic male mice F1 (CBA X C57BL/6j). No leukemoid reaction was observed in these mice after grafting syngeneic strain of urinary bladder carcinoma.", "contents": "[Hematopoietic tissue reactions associated with the growth of syngeneic transplanted tumors in mice]. Hemangiopericytoma growth in syngeneic male mice F1 (CBA X C57BL/bj) led to regular hemopoietic changes: an increase in the spleen weight, spleen cell count, in the number of colony-forming units (CFU). It also induced augmentation of myelopoiesis in the spleen and leukocytosis with a sharp increase of segmented granulocytes in the circulating blood characterized as the \"leukemoid reaction\" syndrome. The latter occurred even when the tumour cells were transplanted into the splenectomized host. Although less marked, this leukemoid reaction was also noted in advanced hepatoma transplanted to syngeneic male mice F1 (CBA X C57BL/6j). No leukemoid reaction was observed in these mice after grafting syngeneic strain of urinary bladder carcinoma."}
{"id": "PMID:208683", "title": "[Thermal sensitivity of specific transplantation antigens of the tumor-cell membrane].", "content": "Study of temperature-sensitivity of the tumour specific transplantation antigen (TSTA) on the cell membrane of SV40-induced tumours and spontaneous hepatoma of inbred Syrian hamsters, as well as in the monkey cells infected in vitro with SV40 virus (ts-mutant) demonstrated high thermolability of TSTA. Heating such cells at 56 degrees C for 30-60 min led to complete loss of their immunogenic activity. Moreover, in the animals immunized with heated tumour cells the test-tumour cell growth was regularly enhanced.", "contents": "[Thermal sensitivity of specific transplantation antigens of the tumor-cell membrane]. Study of temperature-sensitivity of the tumour specific transplantation antigen (TSTA) on the cell membrane of SV40-induced tumours and spontaneous hepatoma of inbred Syrian hamsters, as well as in the monkey cells infected in vitro with SV40 virus (ts-mutant) demonstrated high thermolability of TSTA. Heating such cells at 56 degrees C for 30-60 min led to complete loss of their immunogenic activity. Moreover, in the animals immunized with heated tumour cells the test-tumour cell growth was regularly enhanced."}
{"id": "PMID:208684", "title": "[Participation of hypothalamic adrenergic and cholinergic systems in the regulation of pituitary adrenocorticotropic function].", "content": "Experiments were conducted on male rats; a study was made of the activity of pituitary-adrenal cortex system under conditions of electrolyte destruction of various hypothalamic areas. Pharmacological analysis pointed to the irregular distribution in the hypothalamus of the cholinergic and adrenergic systems controlling the secretion of ACTH-glucocorticoids. As suggested, the cholinergic systems are situated in the mammillary region, alpha-adrenergic ones--in the anterior or the posterior regions of the hypothalamus, and beta-adrenergic receptors--in the ventromedial nuclei of the hypothalamus. The latter possibly play an inhibitory role.", "contents": "[Participation of hypothalamic adrenergic and cholinergic systems in the regulation of pituitary adrenocorticotropic function]. Experiments were conducted on male rats; a study was made of the activity of pituitary-adrenal cortex system under conditions of electrolyte destruction of various hypothalamic areas. Pharmacological analysis pointed to the irregular distribution in the hypothalamus of the cholinergic and adrenergic systems controlling the secretion of ACTH-glucocorticoids. As suggested, the cholinergic systems are situated in the mammillary region, alpha-adrenergic ones--in the anterior or the posterior regions of the hypothalamus, and beta-adrenergic receptors--in the ventromedial nuclei of the hypothalamus. The latter possibly play an inhibitory role."}
{"id": "PMID:208685", "title": "[Hyperlipidemia in rats with chronic renal failure].", "content": "The character of hyperlipidemia was studied in rats with chronic uremia induced by subtotal nephrectomy--5/6 of the renal tissue was removed. 13 to 30 weeks after this operation the blood serum cholesterol and phospholipid concentration almost doubled. Hyperlipidemia was more pronounced in rats with high azotemia (blood urea nitrogen--BUN). No elevation of serum tryglycerides occurred. Total serum beta- and pre-beta-lipoproteins determined nephelometrically increased significantly only with the BUN level of over 80 mg%. Lipoprotein disc electrophoresis of the serum in rats with uremia demonstrated a distinct rise of alpha-lipoproteins and a slight--of beta-lipoproteins; postheparin lipolytic activity of the plasma was normal. Experimental rats displayed massive proteinuria, but hypoproteinuria was insignificant.", "contents": "[Hyperlipidemia in rats with chronic renal failure]. The character of hyperlipidemia was studied in rats with chronic uremia induced by subtotal nephrectomy--5/6 of the renal tissue was removed. 13 to 30 weeks after this operation the blood serum cholesterol and phospholipid concentration almost doubled. Hyperlipidemia was more pronounced in rats with high azotemia (blood urea nitrogen--BUN). No elevation of serum tryglycerides occurred. Total serum beta- and pre-beta-lipoproteins determined nephelometrically increased significantly only with the BUN level of over 80 mg%. Lipoprotein disc electrophoresis of the serum in rats with uremia demonstrated a distinct rise of alpha-lipoproteins and a slight--of beta-lipoproteins; postheparin lipolytic activity of the plasma was normal. Experimental rats displayed massive proteinuria, but hypoproteinuria was insignificant."}
{"id": "PMID:208686", "title": "[Beta-adrenoreceptors on the surface membranes of lymphocytes and macrophages].", "content": "In experiments in vivo and in vitro on sensitized and intact guinea pigs and Wistar rats the effect of beta-adrenergic stimulants (adrenaline and izoproterenol) and a beta-adrenergic blocker (propranalol) on lymphocytolysis and the reaction of macrophage adherence inhibition was studied. Adrenaline and izoproterenol were shown to inhibit the antigen interaction with both sensitized and intact cells. Restoring the sensitivity of cells to the antigen, propranalol destroys the defensive action of adrenaline and isoproterenol.", "contents": "[Beta-adrenoreceptors on the surface membranes of lymphocytes and macrophages]. In experiments in vivo and in vitro on sensitized and intact guinea pigs and Wistar rats the effect of beta-adrenergic stimulants (adrenaline and izoproterenol) and a beta-adrenergic blocker (propranalol) on lymphocytolysis and the reaction of macrophage adherence inhibition was studied. Adrenaline and izoproterenol were shown to inhibit the antigen interaction with both sensitized and intact cells. Restoring the sensitivity of cells to the antigen, propranalol destroys the defensive action of adrenaline and isoproterenol."}
{"id": "PMID:208687", "title": "[Characterization of the viral-type nucleotide sequences detected in the RNA of human leukaemic cells by probes of murine and simian origins (author's transl)].", "content": "Molecular hybridization techniques were used for searching nucleic acid sequences homologous to murine and simian oncornaviral genomes in the RNA of various categories of human leukaemic cells. We report attempts to characterize the sequences that were detected in defined categories of leukemias. It is shown that: i) although there is some correlation between the two probes used in our study with regard to the positivity or the negativity of the tests for the same leukaemic cases, there are also some discrepancies since some of the cases are positive with one probe and negative with the other; ii) the common sequences of the two probes when isolated, were ineffective to detect any complementary sequences in leukemic cases which were scored as positive when the entire probes were used; iii) the complementary sequences detected in three positive cases of acute myelogenous leukemias by a recycled probe are additive and therefore most probably distributed along the viral genome.", "contents": "[Characterization of the viral-type nucleotide sequences detected in the RNA of human leukaemic cells by probes of murine and simian origins (author's transl)]. Molecular hybridization techniques were used for searching nucleic acid sequences homologous to murine and simian oncornaviral genomes in the RNA of various categories of human leukaemic cells. We report attempts to characterize the sequences that were detected in defined categories of leukemias. It is shown that: i) although there is some correlation between the two probes used in our study with regard to the positivity or the negativity of the tests for the same leukaemic cases, there are also some discrepancies since some of the cases are positive with one probe and negative with the other; ii) the common sequences of the two probes when isolated, were ineffective to detect any complementary sequences in leukemic cases which were scored as positive when the entire probes were used; iii) the complementary sequences detected in three positive cases of acute myelogenous leukemias by a recycled probe are additive and therefore most probably distributed along the viral genome."}
{"id": "PMID:208688", "title": "[Synovialo-sarcoma of the laryngopharynx: electron microscopic study (author's transl)].", "content": "The authors report a new case of synovialo sarcoma of the laryngo-pharynx by optic and electron microscopy. Ultrastructural features were similar to those of joint synovialo-sarcoma, i-e, showing glandular like and spindle cell componments. Both of these shared several ultrastructural characteristics, favouring the hypothesis of a common origin. The site and the fine structure of this tumor are discussed according to the literature.", "contents": "[Synovialo-sarcoma of the laryngopharynx: electron microscopic study (author's transl)]. The authors report a new case of synovialo sarcoma of the laryngo-pharynx by optic and electron microscopy. Ultrastructural features were similar to those of joint synovialo-sarcoma, i-e, showing glandular like and spindle cell componments. Both of these shared several ultrastructural characteristics, favouring the hypothesis of a common origin. The site and the fine structure of this tumor are discussed according to the literature."}
{"id": "PMID:208690", "title": "Human studies following models of tumorigenesis by DNA tumor viruses in animals.", "content": "The discovery of virus-specific messenger RNA in virus-induced animal tumors has led to the search for messenger RNA in human tumors that can be hybridized with the DNA of known oncogenic viruses. Attention has focused on the adenoviruses, which have produced cancer in laboratory animals and are widespread in man, and on three papovaviruses that have been isolated in human disease and which are oncogenic in hamsters. In other research, the association between human infection with herpesivurs type 2, which is likewise oncogenic in hamsters, and invasive carcinoma of the cervix is being examined. An experimental vaccine is being developed, and nonhuman primate models are being studied as part of this work. Epstein-Barr virus is still another suspected agent of human malignancies, specifically Burkitt's lymphoma and postnasal carcinoma. High prevalence of antigen to hepatitis B virus has been seen to correlate with high incidence of primary liver cell carcinoma, and studies are attempting to elucidate the relationship.", "contents": "Human studies following models of tumorigenesis by DNA tumor viruses in animals. The discovery of virus-specific messenger RNA in virus-induced animal tumors has led to the search for messenger RNA in human tumors that can be hybridized with the DNA of known oncogenic viruses. Attention has focused on the adenoviruses, which have produced cancer in laboratory animals and are widespread in man, and on three papovaviruses that have been isolated in human disease and which are oncogenic in hamsters. In other research, the association between human infection with herpesivurs type 2, which is likewise oncogenic in hamsters, and invasive carcinoma of the cervix is being examined. An experimental vaccine is being developed, and nonhuman primate models are being studied as part of this work. Epstein-Barr virus is still another suspected agent of human malignancies, specifically Burkitt's lymphoma and postnasal carcinoma. High prevalence of antigen to hepatitis B virus has been seen to correlate with high incidence of primary liver cell carcinoma, and studies are attempting to elucidate the relationship."}
{"id": "PMID:208691", "title": "[Subcellular distribution of hypothalamic neurohormones and in vitro stimulation of their release].", "content": "Neuronal compartments can be separated by differential spinning or by centrifugation on continuous or discontinuous density gradients. Application of these fractionation techniques to brain structures containing neurosecretory neurons shows that LHRH, somatostatin and a non dopamine prolactin inhibiting factor (PIF) are exclusively recovered from synaptosomal fractions. This indicates that biologically and/or immunologically reactive forms of these hormones are almost entirely concentrated in nerve-endings of neurosecretory neurons. In contrast, other neuropeptides - posterior pituitary hormone, but also TRH, a vasoactive intestinal peptide (VIP), substance P or endorphins - are also found in supernatant fractions. The existence of multiple molecular forms of neuropeptides is likely to explain these differences. Current theories postulate that they are synthetized on ribosomes as precursor forms. Their active structure is only achieved by enzymatic splitting of the pre- or the prohormone within nerve endings. This mode of synthesis is probably common to all neuropeptides, although it has only been well substantiated in a few cases, in particular for the hormones of the posterior pituitary. Thus, the lack of immunologically detectable LHRH or SRIF outside the synaptosomal fraction may reflect masking of the active immunological sites by inert peptide chains associated with prohormonal forms. Fractionation methods can also be applied to physiological or pharmacological experiments. In particular, they permit to characterize, on presynaptic membranes of neurosecretory neurons, specific receptors to neurotransmitters involved in the control of neurohormone secretion. Interaction of dopamine and acetylcholine with LHRH and CRF release are presented as examples of such applications.", "contents": "[Subcellular distribution of hypothalamic neurohormones and in vitro stimulation of their release]. Neuronal compartments can be separated by differential spinning or by centrifugation on continuous or discontinuous density gradients. Application of these fractionation techniques to brain structures containing neurosecretory neurons shows that LHRH, somatostatin and a non dopamine prolactin inhibiting factor (PIF) are exclusively recovered from synaptosomal fractions. This indicates that biologically and/or immunologically reactive forms of these hormones are almost entirely concentrated in nerve-endings of neurosecretory neurons. In contrast, other neuropeptides - posterior pituitary hormone, but also TRH, a vasoactive intestinal peptide (VIP), substance P or endorphins - are also found in supernatant fractions. The existence of multiple molecular forms of neuropeptides is likely to explain these differences. Current theories postulate that they are synthetized on ribosomes as precursor forms. Their active structure is only achieved by enzymatic splitting of the pre- or the prohormone within nerve endings. This mode of synthesis is probably common to all neuropeptides, although it has only been well substantiated in a few cases, in particular for the hormones of the posterior pituitary. Thus, the lack of immunologically detectable LHRH or SRIF outside the synaptosomal fraction may reflect masking of the active immunological sites by inert peptide chains associated with prohormonal forms. Fractionation methods can also be applied to physiological or pharmacological experiments. In particular, they permit to characterize, on presynaptic membranes of neurosecretory neurons, specific receptors to neurotransmitters involved in the control of neurohormone secretion. Interaction of dopamine and acetylcholine with LHRH and CRF release are presented as examples of such applications."}
{"id": "PMID:208692", "title": "[Specific role of sex steroids on the pituitary level. Sex steroids and anterior pituitary secretion].", "content": "Although sex steroids were known to play a role in the control of LH, FSH, TSH and prolactin secretion, in vivo experiments could not discriminate between hypothalamic and pituitary sites of action. In this study, the specific action of sex steroids at the anterior pituitary level could be achieved using rat adenohypophyseal cells in primary culture. While estrogens stimulated the sensitivity of the LH and FSH responses to LHRH, androgens had differential effects on the secretion of the two gonadotropins: marked inhibition of LH and stimulation of FSH secretion. Progesterone, on the other hand, while having no effect in the absence of estrogens, could reverse the stimulatory effect of estrogens on LH release while it led to a stimulation of FSH secretion. Estrogens and thyroid hormone exert respective stimulatory and inhibitory effects on TSH secretion by a direct action at the pituitary level. These effects appear to be mediated changes of the level of adenohy-pophyseal TRH receptors. A close correlation was observed between the specificity of binding of the dopamine agonist (3H)dihydroergocryptine and the control of prolactin release in cells in culture, thus supporting the physiological importance of the dopamine receptor in the control of prolactin release. The high degree precision of this system permits assessment of activity of not only dopamine agonists and antagonists, but also of compounds having mixed agonist-antagonistic activity. Preincubation of anterior pituitary cells with 17beta-estradiol not only stimulated basal and TRH-induced prolactin release but, more unexpectedly, led to an almost complete reversal of the inhibitory effect of dopamine agonists on prolactin secretion. Besides its own interest, the adenohypophyseal cell culture system could well be used as a model system for study of the interaction between estrogens and dopaminergic action.", "contents": "[Specific role of sex steroids on the pituitary level. Sex steroids and anterior pituitary secretion]. Although sex steroids were known to play a role in the control of LH, FSH, TSH and prolactin secretion, in vivo experiments could not discriminate between hypothalamic and pituitary sites of action. In this study, the specific action of sex steroids at the anterior pituitary level could be achieved using rat adenohypophyseal cells in primary culture. While estrogens stimulated the sensitivity of the LH and FSH responses to LHRH, androgens had differential effects on the secretion of the two gonadotropins: marked inhibition of LH and stimulation of FSH secretion. Progesterone, on the other hand, while having no effect in the absence of estrogens, could reverse the stimulatory effect of estrogens on LH release while it led to a stimulation of FSH secretion. Estrogens and thyroid hormone exert respective stimulatory and inhibitory effects on TSH secretion by a direct action at the pituitary level. These effects appear to be mediated changes of the level of adenohy-pophyseal TRH receptors. A close correlation was observed between the specificity of binding of the dopamine agonist (3H)dihydroergocryptine and the control of prolactin release in cells in culture, thus supporting the physiological importance of the dopamine receptor in the control of prolactin release. The high degree precision of this system permits assessment of activity of not only dopamine agonists and antagonists, but also of compounds having mixed agonist-antagonistic activity. Preincubation of anterior pituitary cells with 17beta-estradiol not only stimulated basal and TRH-induced prolactin release but, more unexpectedly, led to an almost complete reversal of the inhibitory effect of dopamine agonists on prolactin secretion. Besides its own interest, the adenohypophyseal cell culture system could well be used as a model system for study of the interaction between estrogens and dopaminergic action."}
{"id": "PMID:208693", "title": "Interaction of alpha-melanotropin with central dopamine systems: role of hormonal state and molecular structure.", "content": "The tubero-infundibular and nigrostriatal DA neurone systems of rats respond to systemic (i.p.) injection of alpha-MSH (2-100 microgram/kg). The response of the tubero-infundibular (arcuate) DA neurones, an increase in cellular fluorescence intensity which can be interpreted as a sign of increased neuronal activity, is essentially the same in males, estrogen-progesterone-pretreated ovariectomized females and hypophysectomized males, whereas the type of response elicited by alpha-MSH in the nigral DA neurones depends upon the hormonal state of the animal. Differences between the two DA neurone groups exist also with regard to the effects of peptide fragments containing the two active sites of the alpha-MSH molecule. Results of lesion experiments in the lower brainstem (area postrema) and of blockade of muscarinic mechanisms by atropine further point to differences in the mechanisms underlying the peptide effects on the two neurone systems. The reaction of the tubero-infundibular DA system (which controls the pars intermedia of the pituitary) can be considered to reflect the activation of a feedback mechanism on MSH secretion, while the functional counterpart of the changes observed in the nigral system remains unknown at the present time.", "contents": "Interaction of alpha-melanotropin with central dopamine systems: role of hormonal state and molecular structure. The tubero-infundibular and nigrostriatal DA neurone systems of rats respond to systemic (i.p.) injection of alpha-MSH (2-100 microgram/kg). The response of the tubero-infundibular (arcuate) DA neurones, an increase in cellular fluorescence intensity which can be interpreted as a sign of increased neuronal activity, is essentially the same in males, estrogen-progesterone-pretreated ovariectomized females and hypophysectomized males, whereas the type of response elicited by alpha-MSH in the nigral DA neurones depends upon the hormonal state of the animal. Differences between the two DA neurone groups exist also with regard to the effects of peptide fragments containing the two active sites of the alpha-MSH molecule. Results of lesion experiments in the lower brainstem (area postrema) and of blockade of muscarinic mechanisms by atropine further point to differences in the mechanisms underlying the peptide effects on the two neurone systems. The reaction of the tubero-infundibular DA system (which controls the pars intermedia of the pituitary) can be considered to reflect the activation of a feedback mechanism on MSH secretion, while the functional counterpart of the changes observed in the nigral system remains unknown at the present time."}
{"id": "PMID:208694", "title": "[Hypothalamic factors in the human fetal brain: their role in the ontogeny of fetal hypophyseal functions].", "content": "The anterior pituitary gland of the human fetus has the ability of synthetizing, storing and secreting hormones early during gestation. The patterns of plasma concentrations of hGH, ACTH, LH and FSH during gestation indicate a maximum of secretion at mid-gestation followed by a progressive decrease of these concentrations until term. In contrast, the secretions of PRL and TSH are moderate at mid-gestation and only increase in the last trimester of gestation. Effective control by the central nervous system (CNS) of the pituitary secretions is still immature at mid-gestation. The presence of releasing factors in the fetal hypothalamus has been established (TRF, LRF, somatostatine) and it was postulated that early in life, relatively autonomous and unrestrained secretion of hypothalamic hypophysiotropic releasing factors occurs and, later in development, there was a maturation of inhibitory or restraining influences mediated via the CNS that modulate the secretion of the fetal adenohypophyseal hormones. Observations made with anencephalic newborns confirm that a functional hypothalamus is necessary for the secretions of each of the hormones of the anterior pituitary gland with the exceptiion of PRL, the secretion of which is normal in anencephaly. Although somatostatin probably participates in the regulation of hGH during fetal life, it appears evident that this regulation can only be fully understood with the existence of a GRF (Growth Hormone Releasing Factor).", "contents": "[Hypothalamic factors in the human fetal brain: their role in the ontogeny of fetal hypophyseal functions]. The anterior pituitary gland of the human fetus has the ability of synthetizing, storing and secreting hormones early during gestation. The patterns of plasma concentrations of hGH, ACTH, LH and FSH during gestation indicate a maximum of secretion at mid-gestation followed by a progressive decrease of these concentrations until term. In contrast, the secretions of PRL and TSH are moderate at mid-gestation and only increase in the last trimester of gestation. Effective control by the central nervous system (CNS) of the pituitary secretions is still immature at mid-gestation. The presence of releasing factors in the fetal hypothalamus has been established (TRF, LRF, somatostatine) and it was postulated that early in life, relatively autonomous and unrestrained secretion of hypothalamic hypophysiotropic releasing factors occurs and, later in development, there was a maturation of inhibitory or restraining influences mediated via the CNS that modulate the secretion of the fetal adenohypophyseal hormones. Observations made with anencephalic newborns confirm that a functional hypothalamus is necessary for the secretions of each of the hormones of the anterior pituitary gland with the exceptiion of PRL, the secretion of which is normal in anencephaly. Although somatostatin probably participates in the regulation of hGH during fetal life, it appears evident that this regulation can only be fully understood with the existence of a GRF (Growth Hormone Releasing Factor)."}
{"id": "PMID:208695", "title": "The participation of luteinizing hormone releasing hormone (LRH) in the process of sexual maturation.", "content": "Precious pubertal ovulation and premature steroid-induced gonadotropin surges were triggered in 23-day old rats by unilateral electrolytic lesions placed in the basal hypothalamus. Attempts were made to reproduce both aspects of precocious sexual maturation by repeated injections or prolonged infusion of Luteinizing Hormone Releasing Hormone (LRH) or by repeated administration of the potent and long-acting analog (D-Leu6, des-Gly-NH2(10))-LRH-ethylamide. Neither effect of the brain lesion was reproduced by LRH or its analog. It is concluded that brain lesions advance puberty in this species by mechanisms not involving the discharge of LRH. The role of the adrenal cortex in providing estrogen precursors required for the induction of ovarian gonadotropin receptors is discussed.", "contents": "The participation of luteinizing hormone releasing hormone (LRH) in the process of sexual maturation. Precious pubertal ovulation and premature steroid-induced gonadotropin surges were triggered in 23-day old rats by unilateral electrolytic lesions placed in the basal hypothalamus. Attempts were made to reproduce both aspects of precocious sexual maturation by repeated injections or prolonged infusion of Luteinizing Hormone Releasing Hormone (LRH) or by repeated administration of the potent and long-acting analog (D-Leu6, des-Gly-NH2(10))-LRH-ethylamide. Neither effect of the brain lesion was reproduced by LRH or its analog. It is concluded that brain lesions advance puberty in this species by mechanisms not involving the discharge of LRH. The role of the adrenal cortex in providing estrogen precursors required for the induction of ovarian gonadotropin receptors is discussed."}
{"id": "PMID:208696", "title": "Studies on polypeptide receptors a critical view on the mechanism of ACTH action.", "content": "Recent work on ACTH receptors in adrenal cells and adipocytes is reviewed. It is suggested that ACTH acts on two types of receptor: an adenylate cyclase receptor and another one that helps to guide cAMP into the correct compartment. The introduction of the term holoreceptor to indicate a unit that is recognized by the hormone and is able to produce a measurable effect, and of the terms discriminator, transmitter and effector to indicate the functional subunits of the holoreceptor is suggested as a measure enhancing clarity and flexibility of communication in this very complex field.", "contents": "Studies on polypeptide receptors a critical view on the mechanism of ACTH action. Recent work on ACTH receptors in adrenal cells and adipocytes is reviewed. It is suggested that ACTH acts on two types of receptor: an adenylate cyclase receptor and another one that helps to guide cAMP into the correct compartment. The introduction of the term holoreceptor to indicate a unit that is recognized by the hormone and is able to produce a measurable effect, and of the terms discriminator, transmitter and effector to indicate the functional subunits of the holoreceptor is suggested as a measure enhancing clarity and flexibility of communication in this very complex field."}
{"id": "PMID:208697", "title": "Effects of releasing factors on hypothalamic neurones.", "content": "Our previous reports on the effect of locally applied polyeptides such as ACTH, the releasing factors TRF and LRF on single unit activity of hypothalamic neurones have been confirmed and extended by several workers. These polypeptides also exhibit behavioural effects. The concept that such hormonal polypeptides may exert neurotransmitter as well as neuromodulator function has gradually become acceptable.", "contents": "Effects of releasing factors on hypothalamic neurones. Our previous reports on the effect of locally applied polyeptides such as ACTH, the releasing factors TRF and LRF on single unit activity of hypothalamic neurones have been confirmed and extended by several workers. These polypeptides also exhibit behavioural effects. The concept that such hormonal polypeptides may exert neurotransmitter as well as neuromodulator function has gradually become acceptable."}
{"id": "PMID:208701", "title": "Mechanism of alpha-melanotropin action.", "content": "A structure-function study of alpha-melanotropin has shown that this tridecapeptide consists of two message sequences, (-Glu)-His-Phe-Arg-Trp- and -Gly-Lys-Pro-Val-NH2, and a potentiator sequence, Ac.Ser-Tyr-Ser-Met-(Glu-), when acting on its melanophore receptors. The key elements of the message, -Phe-Arg- and -Lys-Pro-, do not correspond exactly to those responsible for eliciting the effect in other tissues. It appears that alpha-MSH contains more information than would be necessary to interact with only one complementary receptor site; therefore, the topography of the hormone exposed to the binding site may be different on contact with the receptors of different target cells. To further investigate this aspect, new methods for the isolation and characterization of functional receptors must be developed. We are investigating the use of chemically well-defined, biologically active, covalent hormone-macromolecule complexes for this purpose. Another approach utilizes model receptors with a recognition pattern similar to that of the biological receptor, as described in this communication for certain highly specific antibodies.", "contents": "Mechanism of alpha-melanotropin action. A structure-function study of alpha-melanotropin has shown that this tridecapeptide consists of two message sequences, (-Glu)-His-Phe-Arg-Trp- and -Gly-Lys-Pro-Val-NH2, and a potentiator sequence, Ac.Ser-Tyr-Ser-Met-(Glu-), when acting on its melanophore receptors. The key elements of the message, -Phe-Arg- and -Lys-Pro-, do not correspond exactly to those responsible for eliciting the effect in other tissues. It appears that alpha-MSH contains more information than would be necessary to interact with only one complementary receptor site; therefore, the topography of the hormone exposed to the binding site may be different on contact with the receptors of different target cells. To further investigate this aspect, new methods for the isolation and characterization of functional receptors must be developed. We are investigating the use of chemically well-defined, biologically active, covalent hormone-macromolecule complexes for this purpose. Another approach utilizes model receptors with a recognition pattern similar to that of the biological receptor, as described in this communication for certain highly specific antibodies."}
{"id": "PMID:208702", "title": "Depression of evoked potentials in brain slices by adenosine compounds.", "content": "1 A study has been made of the action of adenosine on surface slices of guinea-pig olfactory cortex in vitro. 2 With extracellular recordings from the pial surface and stimulation of the presynaptic input, the lateral olfactory tract (LOT) generated a monosynaptic negative wave representing dendritic excitatory potentials. This negative wave was depressed by bath application of 1 micron adenosine with increasing effect up to 1 mM. Adenosine 5'--triphosphate (ATP), adenosine 5'-monophosphate (AMP) and cyclic adenosine 3',5'-monophosphate (cyclic AMP) had similar depressant actions. Adenine and guanosine were very weak depressants. 3 Theophylline concentrations in the range 10 micron to 3 mM progressively antagonized the action of adenosine. 4 Dibuyryl cyclic AMP (100 micron) and agents which increase intracellular cyclic AMP were not depressants, suggesting that the action of adenosine was not cyclic AMP-mediated. 5 Intracellular recordings confirmed the depressant effect of adenosine on excitatory potentials generated by LOT stimulation and also showed that postsynatpic action potentials and the membrane of the soma were unaffected by adenosine. 6 Since presynaptic action potentials were also unaffected by adenosine, these experiments suggest that adenosine reduces excitatory transmission at LOT synapses and fortifies the idea that adenosine has a 'neurohumoral' action.", "contents": "Depression of evoked potentials in brain slices by adenosine compounds. 1 A study has been made of the action of adenosine on surface slices of guinea-pig olfactory cortex in vitro. 2 With extracellular recordings from the pial surface and stimulation of the presynaptic input, the lateral olfactory tract (LOT) generated a monosynaptic negative wave representing dendritic excitatory potentials. This negative wave was depressed by bath application of 1 micron adenosine with increasing effect up to 1 mM. Adenosine 5'--triphosphate (ATP), adenosine 5'-monophosphate (AMP) and cyclic adenosine 3',5'-monophosphate (cyclic AMP) had similar depressant actions. Adenine and guanosine were very weak depressants. 3 Theophylline concentrations in the range 10 micron to 3 mM progressively antagonized the action of adenosine. 4 Dibuyryl cyclic AMP (100 micron) and agents which increase intracellular cyclic AMP were not depressants, suggesting that the action of adenosine was not cyclic AMP-mediated. 5 Intracellular recordings confirmed the depressant effect of adenosine on excitatory potentials generated by LOT stimulation and also showed that postsynatpic action potentials and the membrane of the soma were unaffected by adenosine. 6 Since presynaptic action potentials were also unaffected by adenosine, these experiments suggest that adenosine reduces excitatory transmission at LOT synapses and fortifies the idea that adenosine has a 'neurohumoral' action."}
{"id": "PMID:208703", "title": "Morphine analgesia and cerebral opiate receptors: a developmental study.", "content": "1 Development of the analgesic response to morphine and ontogenesis of central opiate receptors were analyzed in rats 5 to 120 days old. 2 The analgesic effect of morphine increased until day 15, after which it decreased to reach a plateau at about day 30. With phenoperidine, on the other hand, the analgesic effect increased until day 15, remained constant between day 15 and day 30 after which it decreased slowly. 3 The ratio of the amounts of morphine in blood over those in brain increased about 3 fold between day 15 and day 30. 4 Opiate receptors were detected in the brain of newborn rats: stereospecific binding of [3H]-naloxone at 10 and 50 nM indicated the presence of low and high affinity binding sites. 5 The number of [3H]-naloxone binding sites increased rapidly during the second and third week after birth. Their affinity for several opiates remained constant throughout development. 6 These results indicate that the analgesic activity of opiates varies with age: until day 15, the analgesic effect of opiates increases in parallel with the number of opiate brain receptors. Then, the formation of the blood brain barrier introduces an additional step in the regulation of opiate activity.", "contents": "Morphine analgesia and cerebral opiate receptors: a developmental study. 1 Development of the analgesic response to morphine and ontogenesis of central opiate receptors were analyzed in rats 5 to 120 days old. 2 The analgesic effect of morphine increased until day 15, after which it decreased to reach a plateau at about day 30. With phenoperidine, on the other hand, the analgesic effect increased until day 15, remained constant between day 15 and day 30 after which it decreased slowly. 3 The ratio of the amounts of morphine in blood over those in brain increased about 3 fold between day 15 and day 30. 4 Opiate receptors were detected in the brain of newborn rats: stereospecific binding of [3H]-naloxone at 10 and 50 nM indicated the presence of low and high affinity binding sites. 5 The number of [3H]-naloxone binding sites increased rapidly during the second and third week after birth. Their affinity for several opiates remained constant throughout development. 6 These results indicate that the analgesic activity of opiates varies with age: until day 15, the analgesic effect of opiates increases in parallel with the number of opiate brain receptors. Then, the formation of the blood brain barrier introduces an additional step in the regulation of opiate activity."}
{"id": "PMID:208707", "title": "The effect of different calcium concentrations on the inhibitory effect of presynaptic alpha-adrenoceptors in the rat vas deferens.", "content": "The effects of different calcium concentrations on the twitch-inhibitory potency of clonidine and of guanethidine have been examined in the rat isolated vas deferens. Vasa deferentia did not respond to field stimulation at 0.3 Hz in Krebs solution containing 0.325 mmol/1 of calcium. Increasing the calcium concentration to 5.2 mmol/1 caused a concentration-dependent increase in size of the twitch response. The twitch inhibitory potency of clonidine was inversely proportional to the calcium concentration. The inhibitory effect of guanethidine was not influenced by changes in calcium concentration. The results show that the modulation of motor function by presynaptic alpha-adrenoceptors in the rat vas deferens is calcium-dependent.", "contents": "The effect of different calcium concentrations on the inhibitory effect of presynaptic alpha-adrenoceptors in the rat vas deferens. The effects of different calcium concentrations on the twitch-inhibitory potency of clonidine and of guanethidine have been examined in the rat isolated vas deferens. Vasa deferentia did not respond to field stimulation at 0.3 Hz in Krebs solution containing 0.325 mmol/1 of calcium. Increasing the calcium concentration to 5.2 mmol/1 caused a concentration-dependent increase in size of the twitch response. The twitch inhibitory potency of clonidine was inversely proportional to the calcium concentration. The inhibitory effect of guanethidine was not influenced by changes in calcium concentration. The results show that the modulation of motor function by presynaptic alpha-adrenoceptors in the rat vas deferens is calcium-dependent."}
{"id": "PMID:208711", "title": "Comparison of firing patterns and sensory responsiveness between supraoptic and other hypothalamic neurons in the unanesthetized sheep.", "content": "Adult Southdown ewes were surgically prepared with pituitary stimulating electrodes, carotid and jugular cannulae, and a cranial platform-cylinder arrangement for chronic single unit recording. Isolated neurons (n = 112) in the region of the supraoptic nucleus (SON) were identified by pituitary stalk stimulastion as AD + (antidromically invaded) SON neuroendocrine cells (n = 75) or AD--(not antidromically invaded) SON neurons (n = 37). Spontaneous firing pattern distribution and sensory evoked behavior of these SON region neurons were compared with activity recorded from 112 randomly located non-identified neurons of extra-SON areas of the hypothalamus. Spontaneous discharge activity was categorized into six distinct firing pattern types: continuously active slow (CAS), continuously active fast (CAF), continuously active bursting (CAB), continuously active regular (CAR), low frequency bursting (LFB), and high frequency bursting (HFB). These 6 firing pattern types were characterized by computer analysis and their mean order independent statistical parameters compared. Bursting discharge patterns (LFB, HFB, and CAB) were compared with respect to mean burst duration, burst mean firing rate, and interburst interavls. Ninety-three per cent of all neurons maintained a stable discharge pattern in the absence of apparent stimuli. Occasionally CAS and CAF neurons spontaneously generated spike clusters sufficient to give the transient appearance of a bursting discharge pattern and LFB neurons lapsed spontaneously into CAS acitivity. All 6 firing pattern types recorded from non-identified extra-SON neurons were also recorded in the SON region. However, spontaneously discharging AD+ SON neurons exhibited only continuously active slow (CAS), continuously active fast (CAF), and low frequency bursting (LFB) activity. The total absence of high frequency bursting (HFB), continuously active regular (CAR), and continuously active bursting (CAB) patterns of discharge from AD+ SON neurons suggests that AD- SON neurons exhibiting these firing patterns may function as interneurons, pacemaker neurons, or receptor neurons. A significant number of LFB discharging neurons were recorded in widespread extra-SON regions of the hypothalamus, indicating this discharge pattern may not be unique to magnocellular neuroendocrine cells. AD+ SON LFB neurons sampled in this study demonstrated a significantly longer mean interburst interval (20.86 sec) compared to extra-SON LFB neurons (12.43 sec). No AD+ SON neuron tested was significantly sensitive to non-specific sensory arousal or sleep-waking state changes. In extra-SON areas of the hypothalamus, 11 of 75 neurons tested to sensory arousal and 6 of 19 neurons tested to sleep-waking changes responded with significant changes in mean firing rate (MFR); no significant difference between firing pattern types was demonstrated in arousal or sleep-waking sensitivity...", "contents": "Comparison of firing patterns and sensory responsiveness between supraoptic and other hypothalamic neurons in the unanesthetized sheep. Adult Southdown ewes were surgically prepared with pituitary stimulating electrodes, carotid and jugular cannulae, and a cranial platform-cylinder arrangement for chronic single unit recording. Isolated neurons (n = 112) in the region of the supraoptic nucleus (SON) were identified by pituitary stalk stimulastion as AD + (antidromically invaded) SON neuroendocrine cells (n = 75) or AD--(not antidromically invaded) SON neurons (n = 37). Spontaneous firing pattern distribution and sensory evoked behavior of these SON region neurons were compared with activity recorded from 112 randomly located non-identified neurons of extra-SON areas of the hypothalamus. Spontaneous discharge activity was categorized into six distinct firing pattern types: continuously active slow (CAS), continuously active fast (CAF), continuously active bursting (CAB), continuously active regular (CAR), low frequency bursting (LFB), and high frequency bursting (HFB). These 6 firing pattern types were characterized by computer analysis and their mean order independent statistical parameters compared. Bursting discharge patterns (LFB, HFB, and CAB) were compared with respect to mean burst duration, burst mean firing rate, and interburst interavls. Ninety-three per cent of all neurons maintained a stable discharge pattern in the absence of apparent stimuli. Occasionally CAS and CAF neurons spontaneously generated spike clusters sufficient to give the transient appearance of a bursting discharge pattern and LFB neurons lapsed spontaneously into CAS acitivity. All 6 firing pattern types recorded from non-identified extra-SON neurons were also recorded in the SON region. However, spontaneously discharging AD+ SON neurons exhibited only continuously active slow (CAS), continuously active fast (CAF), and low frequency bursting (LFB) activity. The total absence of high frequency bursting (HFB), continuously active regular (CAR), and continuously active bursting (CAB) patterns of discharge from AD+ SON neurons suggests that AD- SON neurons exhibiting these firing patterns may function as interneurons, pacemaker neurons, or receptor neurons. A significant number of LFB discharging neurons were recorded in widespread extra-SON regions of the hypothalamus, indicating this discharge pattern may not be unique to magnocellular neuroendocrine cells. AD+ SON LFB neurons sampled in this study demonstrated a significantly longer mean interburst interval (20.86 sec) compared to extra-SON LFB neurons (12.43 sec). No AD+ SON neuron tested was significantly sensitive to non-specific sensory arousal or sleep-waking state changes. In extra-SON areas of the hypothalamus, 11 of 75 neurons tested to sensory arousal and 6 of 19 neurons tested to sleep-waking changes responded with significant changes in mean firing rate (MFR); no significant difference between firing pattern types was demonstrated in arousal or sleep-waking sensitivity..."}
{"id": "PMID:208715", "title": "The auditory midbrain of a marsupial: the brush-tailed possum (Trichosurus vulpecula).", "content": "A microelectrode survey was made of the midbrain auditory nuclei of the brushtailed possum (Trichosurus vulpecula), a common Australian marsupial. Information was sought on the tuning characteristics of individual neurones, tonotopic organization and mechanisms of sound localization. It was felt that such information would be of use in future studies of the development and evolution of mammalian hearing. Twelve possums were anaesthetized with ketamine and chloralose-urethane, and recordings were made of extracellular unit discharges in the inferior colliculus during monaural and binaural tonal stimulation. The inferior colliculus of the possum consists of a central nucleus - a darkly stained, densely packed group of cells - flanked laterally by an external nucleus with a lower density of paler cells. Tonotopic organization was demonstrated by discretelytuned elements in the central nucleus, but was not observed in the external nucleus. In the latter region broad and irregular tuning was commonly seen. Most units in both divisions were influenced by binaural stimuli, with patterns of binaural interaction similar to those observed in the cat inferior colliculus. Cells influenced by changes in the interaural time and intensity difference were commonly observed, but only a subclass of these were suited in sensitivity for sound localization. In general, the midbrain auditory system of the possum was similar in unit discharge characteristics and organization to those of the eutherian mammals commonly studied.", "contents": "The auditory midbrain of a marsupial: the brush-tailed possum (Trichosurus vulpecula). A microelectrode survey was made of the midbrain auditory nuclei of the brushtailed possum (Trichosurus vulpecula), a common Australian marsupial. Information was sought on the tuning characteristics of individual neurones, tonotopic organization and mechanisms of sound localization. It was felt that such information would be of use in future studies of the development and evolution of mammalian hearing. Twelve possums were anaesthetized with ketamine and chloralose-urethane, and recordings were made of extracellular unit discharges in the inferior colliculus during monaural and binaural tonal stimulation. The inferior colliculus of the possum consists of a central nucleus - a darkly stained, densely packed group of cells - flanked laterally by an external nucleus with a lower density of paler cells. Tonotopic organization was demonstrated by discretelytuned elements in the central nucleus, but was not observed in the external nucleus. In the latter region broad and irregular tuning was commonly seen. Most units in both divisions were influenced by binaural stimuli, with patterns of binaural interaction similar to those observed in the cat inferior colliculus. Cells influenced by changes in the interaural time and intensity difference were commonly observed, but only a subclass of these were suited in sensitivity for sound localization. In general, the midbrain auditory system of the possum was similar in unit discharge characteristics and organization to those of the eutherian mammals commonly studied."}
{"id": "PMID:208716", "title": "Impaired synaptic potentiation processes in the hippocampus of aged, memory-deficient rats.", "content": "A series of neurophysiological experiments was performed on the Schaffercommissural system of the hippocampus of aged and young anesthetized Fischer rats. The aged Fisher rats were previously found to exhibit retention performance deficits. No obvious differences were found between aged and young animals in amplitude, latency, stimulation threshold, or wave forms of typical synaptic responses when these were elicited by control (0.3 Hz) stimulation pulses. Further, the temporal curves of facilitation during a paired-pulse series were not different in aged and young animals. However, aged and young synapses showed consistently different responses during repetitive stimulation. Synapses of aged animals were deficient in frequency potentiation processes during 12 Hz stimulation; and the aged animals exhibited a delayed rise of post-tetanic synaptic potentiation following a 5 sec, 100 Hz stimulation train. Moreover, aged synapses 'exhausted' more rapidly during continuous 4 Hz stimulation. Throughout these studies a biphasic pattern of potentiation was observed during repetitive stimulation (brief potentiation, depression, renewed potentiation). Aged animals were deficient primarily in development of the second phase of potentiation. This pattern suggests an age-related impairment of some secondary process of potentiation, leading to an increased tendency to synaptic depression during and after stimulation. The possibility that the impaired hippocampal synaptic plasticity may be related to reported deficient behavioral plasticity in the aged animals is considered.", "contents": "Impaired synaptic potentiation processes in the hippocampus of aged, memory-deficient rats. A series of neurophysiological experiments was performed on the Schaffercommissural system of the hippocampus of aged and young anesthetized Fischer rats. The aged Fisher rats were previously found to exhibit retention performance deficits. No obvious differences were found between aged and young animals in amplitude, latency, stimulation threshold, or wave forms of typical synaptic responses when these were elicited by control (0.3 Hz) stimulation pulses. Further, the temporal curves of facilitation during a paired-pulse series were not different in aged and young animals. However, aged and young synapses showed consistently different responses during repetitive stimulation. Synapses of aged animals were deficient in frequency potentiation processes during 12 Hz stimulation; and the aged animals exhibited a delayed rise of post-tetanic synaptic potentiation following a 5 sec, 100 Hz stimulation train. Moreover, aged synapses 'exhausted' more rapidly during continuous 4 Hz stimulation. Throughout these studies a biphasic pattern of potentiation was observed during repetitive stimulation (brief potentiation, depression, renewed potentiation). Aged animals were deficient primarily in development of the second phase of potentiation. This pattern suggests an age-related impairment of some secondary process of potentiation, leading to an increased tendency to synaptic depression during and after stimulation. The possibility that the impaired hippocampal synaptic plasticity may be related to reported deficient behavioral plasticity in the aged animals is considered."}
{"id": "PMID:208719", "title": "The effects of 1,25-dihydroxycholecalciferol on embryonic bone in vitro: a biochemical and histological study.", "content": "Explants from embryonic rat and mouse calvaria were cultivated in the presence of different concentrations of 1, 25-dihydroxycholecalciferol (1, 25-(OH)2D3). The bone resorbing effects of the vitamin D3 metabolite were evaluated by measuring the release of calcium, phosphate, lactate and citrate into the culture medium after 24 h of cultivation. The influence on bone morphology was studied using embryonic mouse radii, in which histological phenomena in the bony, cartilagenous and connective tissue compartments were observed. Both kinds of experiments show that 1, 25-(OH)2D3 has effects on embryonic bone which are typical for high concentrations of parathyroid hormone (PTH). However, the maximal effects on calcium release and on histology are 2.5 times less than those of PTH. In addition, some of the histological features such as the effects on epiphyseal cartilage and on osteoclasts were not observed. 1, 25-(OH)2D3 in concentrations up to 2 X 10(-9) M does not affect basal or PTH-stimulated cAMP levels in embryonic rat calvaria. In a concentration of 1 X 10(-8) M, however, a significant decrease in PTH-stimulated cAMP production was found. It is concluded from these in vitro experiments that (1) 1, 25-(OH)2D3 stimulates bone resorption, and (2) in 1, 25-(OH)2D3-induced bone resorption cAMP is apparently not involved as a second messenger.", "contents": "The effects of 1,25-dihydroxycholecalciferol on embryonic bone in vitro: a biochemical and histological study. Explants from embryonic rat and mouse calvaria were cultivated in the presence of different concentrations of 1, 25-dihydroxycholecalciferol (1, 25-(OH)2D3). The bone resorbing effects of the vitamin D3 metabolite were evaluated by measuring the release of calcium, phosphate, lactate and citrate into the culture medium after 24 h of cultivation. The influence on bone morphology was studied using embryonic mouse radii, in which histological phenomena in the bony, cartilagenous and connective tissue compartments were observed. Both kinds of experiments show that 1, 25-(OH)2D3 has effects on embryonic bone which are typical for high concentrations of parathyroid hormone (PTH). However, the maximal effects on calcium release and on histology are 2.5 times less than those of PTH. In addition, some of the histological features such as the effects on epiphyseal cartilage and on osteoclasts were not observed. 1, 25-(OH)2D3 in concentrations up to 2 X 10(-9) M does not affect basal or PTH-stimulated cAMP levels in embryonic rat calvaria. In a concentration of 1 X 10(-8) M, however, a significant decrease in PTH-stimulated cAMP production was found. It is concluded from these in vitro experiments that (1) 1, 25-(OH)2D3 stimulates bone resorption, and (2) in 1, 25-(OH)2D3-induced bone resorption cAMP is apparently not involved as a second messenger."}
{"id": "PMID:208720", "title": "The interaction of collagenase with hydroxyapatite and related materials and enzymatic properties of the adsorbed enzyme.", "content": "The commercial collagenase from Clostridium histolyticum was adsorbed on hydroxyapatite, on bovine femur shaft and on enamel and dentin powders. The substrate specificity of the adsorbed enzyme tested, with chromophore substrate, azocoll and native collagen, differed from that obtained with the soluble enzyme. The adsorption and the substrate specificity was also dependent on the adsorbent used. A pretreatment of hydroxyapatite with chondroitin sulphate, hyaluronate and DNA lowered the adsorption of collagenase. Phosphate ion caused desorption of the enzyme from hydroxyapatite. Sodium fluoride caused partial desorption of the enzyme from hydroxyapatite and enamel and dentin powders. Colangenase adsorbed on root surfaces of teeth liberated hydroxyproline containing material.", "contents": "The interaction of collagenase with hydroxyapatite and related materials and enzymatic properties of the adsorbed enzyme. The commercial collagenase from Clostridium histolyticum was adsorbed on hydroxyapatite, on bovine femur shaft and on enamel and dentin powders. The substrate specificity of the adsorbed enzyme tested, with chromophore substrate, azocoll and native collagen, differed from that obtained with the soluble enzyme. The adsorption and the substrate specificity was also dependent on the adsorbent used. A pretreatment of hydroxyapatite with chondroitin sulphate, hyaluronate and DNA lowered the adsorption of collagenase. Phosphate ion caused desorption of the enzyme from hydroxyapatite. Sodium fluoride caused partial desorption of the enzyme from hydroxyapatite and enamel and dentin powders. Colangenase adsorbed on root surfaces of teeth liberated hydroxyproline containing material."}
{"id": "PMID:208721", "title": "Radiation induced free radicals as molecular probes in synthetic apatites.", "content": "Free radicals generated in synthetic apatitic calcium phosphates by X-ray radiation were investigated by electron spin resonance (ESR) spectroscopy. Among the species stable enough at -188 degrees C to be identified were hydrogen atoms, phosphate radicals, and oxygen anion radicals. The ESR spectra were markedly dependent on the specific surface of the mineral. Oxygen radicals dominated the spectra of low specific surface samples while phosphate radicals were the predominant species at higher specific surfaces. Our studies suggest that the oxygen radicals are more stable in the bulk of the crystal while the hydrogen atoms and the phosphate radicals are stabilized at or near the crystal surface. It was concluded that the surface species are potentially capable of serving as probes of biologically relevant mineral-organic interfaces.", "contents": "Radiation induced free radicals as molecular probes in synthetic apatites. Free radicals generated in synthetic apatitic calcium phosphates by X-ray radiation were investigated by electron spin resonance (ESR) spectroscopy. Among the species stable enough at -188 degrees C to be identified were hydrogen atoms, phosphate radicals, and oxygen anion radicals. The ESR spectra were markedly dependent on the specific surface of the mineral. Oxygen radicals dominated the spectra of low specific surface samples while phosphate radicals were the predominant species at higher specific surfaces. Our studies suggest that the oxygen radicals are more stable in the bulk of the crystal while the hydrogen atoms and the phosphate radicals are stabilized at or near the crystal surface. It was concluded that the surface species are potentially capable of serving as probes of biologically relevant mineral-organic interfaces."}
{"id": "PMID:208722", "title": "Neuromuscular and cardiovascular depression produced by prolonged exposure to Polymyxin B.", "content": "It has been reported previously that in cats pre-treatment for 24 to 48 hours with neomycin sulphate resulted in a change in the pattern of neuromuscular block subsequently produced with this antibiotic. The unique characteristics of neomycin-induced neuromuscular block observed during acute exposure gave way to a pattern of block usually observed with tubocurarine. In a similar experiment on six cats we have demonstrated that with polymyxin B prolonged exposure did not result in a comparable time-dependent change in the nature of the neuromuscular block it produced, in terms of train-of-four, tetanic, and post-tetanic behaviour of the neurally-elicited muscle response. The differing characteristics of neuromuscular block seen with various antibiotics, e.g. the aminoglycoside neomycin as opposed to the polypeptide polymyxin B, during acute and sub-chronic exposure is stressed. Previously observed ability of 4 aminopyridine 0.6 mg/kg to reverse the neuromuscular and cardiovascular depression during acute exposure to polymyxin B persisted in prolonged exposure.", "contents": "Neuromuscular and cardiovascular depression produced by prolonged exposure to Polymyxin B. It has been reported previously that in cats pre-treatment for 24 to 48 hours with neomycin sulphate resulted in a change in the pattern of neuromuscular block subsequently produced with this antibiotic. The unique characteristics of neomycin-induced neuromuscular block observed during acute exposure gave way to a pattern of block usually observed with tubocurarine. In a similar experiment on six cats we have demonstrated that with polymyxin B prolonged exposure did not result in a comparable time-dependent change in the nature of the neuromuscular block it produced, in terms of train-of-four, tetanic, and post-tetanic behaviour of the neurally-elicited muscle response. The differing characteristics of neuromuscular block seen with various antibiotics, e.g. the aminoglycoside neomycin as opposed to the polypeptide polymyxin B, during acute and sub-chronic exposure is stressed. Previously observed ability of 4 aminopyridine 0.6 mg/kg to reverse the neuromuscular and cardiovascular depression during acute exposure to polymyxin B persisted in prolonged exposure."}
{"id": "PMID:208724", "title": "Purification and some properties of NAD-degrading purine nucleosidase from Aspergillus niger.", "content": "An enzyme which degrades NAD at the adenine-ribose linkage has been purified from the mycelial extract of Aspergillus niger. NADP, deamido-NAD, and purine nucleosides and nucleotides were also susceptible to the hydrolytic cleavage. Pyrimidine- and nicotinamide-ribose linkages were not attacked. The substrate specificity showed that the enzyme may be classified as  a N-ribosyl-purine ribohydrolase (EC 3.2.2.1). The enzyme had a maximum activity in the pH range of 4.0-4.5 toward NAD. The Km values for NAD, 5'-AMP, and inosine were 3.0, 2.9 and 1.6mM respectively.", "contents": "Purification and some properties of NAD-degrading purine nucleosidase from Aspergillus niger. An enzyme which degrades NAD at the adenine-ribose linkage has been purified from the mycelial extract of Aspergillus niger. NADP, deamido-NAD, and purine nucleosides and nucleotides were also susceptible to the hydrolytic cleavage. Pyrimidine- and nicotinamide-ribose linkages were not attacked. The substrate specificity showed that the enzyme may be classified as  a N-ribosyl-purine ribohydrolase (EC 3.2.2.1). The enzyme had a maximum activity in the pH range of 4.0-4.5 toward NAD. The Km values for NAD, 5'-AMP, and inosine were 3.0, 2.9 and 1.6mM respectively."}
{"id": "PMID:208725", "title": "Coisolation of glycophorin A and polyphosphoinositides from human erythrocyte membranes.", "content": "The lipid composition of purified erythrocyte membrane glycophorin was measured. Diphosphoinositide, triphosphoinositide, and phosphatidylserine are the major phospholipids in glycophorin preparation. Nearly all of the radioactive diphosphoinositide and triphosphoinositide extracted from erythrocyte membranes by lithium d\u00efodosalicylate are recoverd in purified glycophorin. There appeared to be no significant enrichment of other acidic membrane phospholipids in the protein. The results do not permit a firm conclusion as to whether the polyphosphoinositides are associated specifically with the membrane protein or whether fortuitous binding has occurred during purification.", "contents": "Coisolation of glycophorin A and polyphosphoinositides from human erythrocyte membranes. The lipid composition of purified erythrocyte membrane glycophorin was measured. Diphosphoinositide, triphosphoinositide, and phosphatidylserine are the major phospholipids in glycophorin preparation. Nearly all of the radioactive diphosphoinositide and triphosphoinositide extracted from erythrocyte membranes by lithium d\u00efodosalicylate are recoverd in purified glycophorin. There appeared to be no significant enrichment of other acidic membrane phospholipids in the protein. The results do not permit a firm conclusion as to whether the polyphosphoinositides are associated specifically with the membrane protein or whether fortuitous binding has occurred during purification."}
{"id": "PMID:208727", "title": "Preparation of cell populations with stabilized erythropoietic potential from the primitive streak chick blastodisc: some implications for control of gastrulation.", "content": "Improved methods for preparation from primitive streak chick blastodiscs of cell suspensions capable of forming erythroid cells in culture have been developed. When blastodiscs were preincubayed with hyaluronidase in the absence of collagenase before cell dispersion and a high concentration of methyl-alpha-mannoside was present in all media, the yields of cells were some 10-fold higher than those obtained by former procedures. Cell suspensions obtained consisted almost entirely of viable cells, yielded large numbers of free mature erythrocytes in liquid culture, and formed erythroid colonies and bursts in solidified medium. The capacity to form differentiated cells after resedimenrtation through Ficoll density gradients was partly stabilized. Addition of gee yolk homogenate to the blastodiscs immediately following treatment with hyaluronidase and to all media used thereafter largely stabilized the capacity to form erythroid cells during resedimentation through Ficoll density gradients. Possible relevance of observations made during development of the procedures to the control of onset of cell migration in the process of gastrulation is indicated.", "contents": "Preparation of cell populations with stabilized erythropoietic potential from the primitive streak chick blastodisc: some implications for control of gastrulation. Improved methods for preparation from primitive streak chick blastodiscs of cell suspensions capable of forming erythroid cells in culture have been developed. When blastodiscs were preincubayed with hyaluronidase in the absence of collagenase before cell dispersion and a high concentration of methyl-alpha-mannoside was present in all media, the yields of cells were some 10-fold higher than those obtained by former procedures. Cell suspensions obtained consisted almost entirely of viable cells, yielded large numbers of free mature erythrocytes in liquid culture, and formed erythroid colonies and bursts in solidified medium. The capacity to form differentiated cells after resedimenrtation through Ficoll density gradients was partly stabilized. Addition of gee yolk homogenate to the blastodiscs immediately following treatment with hyaluronidase and to all media used thereafter largely stabilized the capacity to form erythroid cells during resedimentation through Ficoll density gradients. Possible relevance of observations made during development of the procedures to the control of onset of cell migration in the process of gastrulation is indicated."}
{"id": "PMID:208731", "title": "Purification of the heat-stable inhibitor protein of the Ca2+-activated cyclic nucleotide phosphodiesterase by affinity chromatography.", "content": "The recently discovered heat-stable inhibitor protein of the Ca2+-activated cyclic nucleotide phosphodiesterase (Sharma, R. K., Wirch, E. & Warg, J. H. (1978) J. Biol. Chem., in press) has been purified 238 214-fold from bovine brain extract using an affinity column of the modulator protein--Sepharose 4B conjugate. The purified sample appears to be homogeneous as judged by sodium dodecyl sulphate (SDS) gel electrophoresis. The protein band has a mobility corresponding to that of a polypeptide of molecular weight 68 000. Since the heat-stable inhibitor protein has a molecular weight of 70 000 under nondenaturing conditions, it suggests that it is a monomeric protein. The protein has no inhibitory activity toward the cAMP-dependent protein kinase or protein phosphatase. The purified sample has been tested for various enzyme activities which include ATPase, GTPase, cAMP phosphodiesterase, cGMP phosphodiesterase, 5'-nucleotidase, and protein kinase. None of these activities are exhibited by the purified sample.", "contents": "Purification of the heat-stable inhibitor protein of the Ca2+-activated cyclic nucleotide phosphodiesterase by affinity chromatography. The recently discovered heat-stable inhibitor protein of the Ca2+-activated cyclic nucleotide phosphodiesterase (Sharma, R. K., Wirch, E. & Warg, J. H. (1978) J. Biol. Chem., in press) has been purified 238 214-fold from bovine brain extract using an affinity column of the modulator protein--Sepharose 4B conjugate. The purified sample appears to be homogeneous as judged by sodium dodecyl sulphate (SDS) gel electrophoresis. The protein band has a mobility corresponding to that of a polypeptide of molecular weight 68 000. Since the heat-stable inhibitor protein has a molecular weight of 70 000 under nondenaturing conditions, it suggests that it is a monomeric protein. The protein has no inhibitory activity toward the cAMP-dependent protein kinase or protein phosphatase. The purified sample has been tested for various enzyme activities which include ATPase, GTPase, cAMP phosphodiesterase, cGMP phosphodiesterase, 5'-nucleotidase, and protein kinase. None of these activities are exhibited by the purified sample."}
{"id": "PMID:208733", "title": "A comparison of some immunological characteristics of very low density lipoproteins of normal and hypercholesterolemic rat sera.", "content": "The immunological characteristics of a very low density lipoproteins (VLDL) from normal and hypercholesterolemic rat sera were compared using polyspecific antisera to VLDL and high density lipoproteins (HDL) and monospecific antisera to apo-B, apo-C, apo-A-I, and apo-E. Ultracentrifugally isolated VLDL from normal serum were studied by immunodiffusion and found to contain both discrete and associated (with apo-B) apo-C and apo-E, probably in the form of lipid-containing lipoproteins. However, immunoelectrophoresis of whole serum revealed only an associated form of the liporpotein having pre-beta mobility (i.e., VLDL), suggesting that the presence of discrete lipoproteins in isolated VLDL, each containing a single apoprotein family, may represent ultracentrifugal artifacts. Ultracentrifugally isolated VLDL from diet-induced hypercholesterolemic rat serum contained only trace amounts of apo-C and large quantities of apo-E, both of which were totally associated with apo-B. VLDL isolated by ultracentrifugation from perfusate of normal and hypercholesterolemic livers contained only associated lipoprotein complexes made up of apo-B, apo-C, and apo-E in the former but only apo-B and apo-E in the latter. These data suggest that normal VLDL are secreted as lipoprotein complexes containing apo-B, apo-C, and apo-E, which may become destabilized in the circulation. However, VLDL from hypercholesterolemic serum shows a marked diminution in the quantity of apo-C as indicated by the relative incorporation of [3H]leucine in vivo and by polyacrylamide gel electrophoresis of apo-VLDL.", "contents": "A comparison of some immunological characteristics of very low density lipoproteins of normal and hypercholesterolemic rat sera. The immunological characteristics of a very low density lipoproteins (VLDL) from normal and hypercholesterolemic rat sera were compared using polyspecific antisera to VLDL and high density lipoproteins (HDL) and monospecific antisera to apo-B, apo-C, apo-A-I, and apo-E. Ultracentrifugally isolated VLDL from normal serum were studied by immunodiffusion and found to contain both discrete and associated (with apo-B) apo-C and apo-E, probably in the form of lipid-containing lipoproteins. However, immunoelectrophoresis of whole serum revealed only an associated form of the liporpotein having pre-beta mobility (i.e., VLDL), suggesting that the presence of discrete lipoproteins in isolated VLDL, each containing a single apoprotein family, may represent ultracentrifugal artifacts. Ultracentrifugally isolated VLDL from diet-induced hypercholesterolemic rat serum contained only trace amounts of apo-C and large quantities of apo-E, both of which were totally associated with apo-B. VLDL isolated by ultracentrifugation from perfusate of normal and hypercholesterolemic livers contained only associated lipoprotein complexes made up of apo-B, apo-C, and apo-E in the former but only apo-B and apo-E in the latter. These data suggest that normal VLDL are secreted as lipoprotein complexes containing apo-B, apo-C, and apo-E, which may become destabilized in the circulation. However, VLDL from hypercholesterolemic serum shows a marked diminution in the quantity of apo-C as indicated by the relative incorporation of [3H]leucine in vivo and by polyacrylamide gel electrophoresis of apo-VLDL."}
{"id": "PMID:208734", "title": "Response of the respiratory tract of calves kept at controlled climatic conditions to bovine Herpesvirus 1 in aerosol.", "content": "Seven experiments with four calves each were conducted in which the calves spent at least four days of adaptation in an environmental chamber and then were subjected to climatic stress in the form of a number of constant ambient temperature and humidity combinations. On the second day of climatic stress the calves were individually exposed to measured numbers of infectious units of bovine herpesvirus 1 (BHV1, virus of infectious bovine rhinotrachetis) in aerosol. The calves were killed seven or eight days later. Mycoplasma were found in some nasal swabs and in one lung. Certain bacteria but no Pasteurella were often isolated from the lungs. Bovine herpesvirus 1 was isolated from chamber air and from most postinoculation nasal swabs, tracheas and lungs. The number of macro- and microscopic lesions did not appear to be influenced by the climatic conditions of the experiments. The histopathological changes in epithelium at all levels of the respiratory tract were described in detail.", "contents": "Response of the respiratory tract of calves kept at controlled climatic conditions to bovine Herpesvirus 1 in aerosol. Seven experiments with four calves each were conducted in which the calves spent at least four days of adaptation in an environmental chamber and then were subjected to climatic stress in the form of a number of constant ambient temperature and humidity combinations. On the second day of climatic stress the calves were individually exposed to measured numbers of infectious units of bovine herpesvirus 1 (BHV1, virus of infectious bovine rhinotrachetis) in aerosol. The calves were killed seven or eight days later. Mycoplasma were found in some nasal swabs and in one lung. Certain bacteria but no Pasteurella were often isolated from the lungs. Bovine herpesvirus 1 was isolated from chamber air and from most postinoculation nasal swabs, tracheas and lungs. The number of macro- and microscopic lesions did not appear to be influenced by the climatic conditions of the experiments. The histopathological changes in epithelium at all levels of the respiratory tract were described in detail."}
{"id": "PMID:208735", "title": "Diagnosis of viral agents associated with neonatal calf diarrhea.", "content": "During this study, 134 samples have been examined for the detection of the viruses associated with neonatal calf diarrhea. The presence of Nebraska viruses (rotavirus and coronavirus) has been demonstrated by using the electron microscope and the fluorescent antibody techniques while the presence of other viruses has been detected by the observation of a cytopathic effect on monolayer cells of calf testis. The Nebraska viruses have been demonstrated in 107 (80%) out of 134 field case specimens. An association of rotaviruses and coronaviruses was found in 58 cases (54%) whilst the coronaviruses and the rotavirus were found singly in 34 cases (53%) and in 15 cases (14%) respectively. Four bovine virus diarrhea viruses, two infectious bovine rhinotracheitis viruses and two enteroviruses have also been isolated in the preceding 107 Nebraska positive specimens. For the detection of the Nebraska viruses, the fluorescent antibody techniques were more sensitive than the electron microscopy. However, those two techniques must be used simultaneously for a better detection of a greatest possible number of cases.", "contents": "Diagnosis of viral agents associated with neonatal calf diarrhea. During this study, 134 samples have been examined for the detection of the viruses associated with neonatal calf diarrhea. The presence of Nebraska viruses (rotavirus and coronavirus) has been demonstrated by using the electron microscope and the fluorescent antibody techniques while the presence of other viruses has been detected by the observation of a cytopathic effect on monolayer cells of calf testis. The Nebraska viruses have been demonstrated in 107 (80%) out of 134 field case specimens. An association of rotaviruses and coronaviruses was found in 58 cases (54%) whilst the coronaviruses and the rotavirus were found singly in 34 cases (53%) and in 15 cases (14%) respectively. Four bovine virus diarrhea viruses, two infectious bovine rhinotracheitis viruses and two enteroviruses have also been isolated in the preceding 107 Nebraska positive specimens. For the detection of the Nebraska viruses, the fluorescent antibody techniques were more sensitive than the electron microscopy. However, those two techniques must be used simultaneously for a better detection of a greatest possible number of cases."}
{"id": "PMID:208736", "title": "The protective antigens of equine herpesvirus type 1.", "content": "Equine herpesvirus type 1 was cultivated in swine testis cell cultures and partially purified by differential centrifugation and centrifugation in a linear sucrose density gradient. The viral envelope was separated from the nucleocapsid by treatment with Rexol 25J followed by sucrose gradient centrifugation. The envelope and nucleocapsid preparations were then electrophoresed in polyacrylamide gel after solubilization with sodium dodecyl sulphate. Hamsters were immunized with various preparations of the partially purified virus, including live or inactivated equine herpesvirus type 1 and viral envelope and nucleocapsid, all derived from the Kentucky D strain of the virus. Challenge of the immunized hamsters, with a hamster-adapted strain of equine herpesvirus type 1 demonstrated protection only in those animals which had been vaccinated with envelope-containing materials. When vaccination was carried out with fractions of electrophoresed envelope or nucleocapsid, protection was induced only by polypeptides of high molecular weight containing a glycoprotein component of the envelope of equine herpesvirus type 1.", "contents": "The protective antigens of equine herpesvirus type 1. Equine herpesvirus type 1 was cultivated in swine testis cell cultures and partially purified by differential centrifugation and centrifugation in a linear sucrose density gradient. The viral envelope was separated from the nucleocapsid by treatment with Rexol 25J followed by sucrose gradient centrifugation. The envelope and nucleocapsid preparations were then electrophoresed in polyacrylamide gel after solubilization with sodium dodecyl sulphate. Hamsters were immunized with various preparations of the partially purified virus, including live or inactivated equine herpesvirus type 1 and viral envelope and nucleocapsid, all derived from the Kentucky D strain of the virus. Challenge of the immunized hamsters, with a hamster-adapted strain of equine herpesvirus type 1 demonstrated protection only in those animals which had been vaccinated with envelope-containing materials. When vaccination was carried out with fractions of electrophoresed envelope or nucleocapsid, protection was induced only by polypeptides of high molecular weight containing a glycoprotein component of the envelope of equine herpesvirus type 1."}
{"id": "PMID:208737", "title": "A complement fixing antigen in the livers of birds infected with an avian leukovirus (erythroblastosis virus).", "content": "Extracts of erythroblastosis affected livers from which much of the structural protein had been removed were prepared by acid denaturation. These extracts contained complement fixing \"soluble\" antigen in a form which was not associated with viral or subviral particles. Ultracentrifugation can be of assistance in separating complement fixation activity from contaminating material in these extracts.", "contents": "A complement fixing antigen in the livers of birds infected with an avian leukovirus (erythroblastosis virus). Extracts of erythroblastosis affected livers from which much of the structural protein had been removed were prepared by acid denaturation. These extracts contained complement fixing \"soluble\" antigen in a form which was not associated with viral or subviral particles. Ultracentrifugation can be of assistance in separating complement fixation activity from contaminating material in these extracts."}
{"id": "PMID:208738", "title": "Duration of active and colostrum-derived passive antibodies to bovine viral diarrhea virus in calves.", "content": "Duration of active and colostrum-derived passive antibodies to bovine viral diarrhea virus was studied in 14 calves. Five calves born with actively induced antibodies to bovine viral diarrhea virus retained high titers during the year of observation. Colostrum-derived antibodies to bovine viral diarrhea virus in nine calves declined at an expected rate for the first four to six months of age. However, titers of six of these calves increased at five to eight months of age and either remained constant or increased through one year of age. Bovine viral diarrhea virus antibody titers of the other three calves declined at a constant rate to less than 1:4 by nine to 12 months of age.", "contents": "Duration of active and colostrum-derived passive antibodies to bovine viral diarrhea virus in calves. Duration of active and colostrum-derived passive antibodies to bovine viral diarrhea virus was studied in 14 calves. Five calves born with actively induced antibodies to bovine viral diarrhea virus retained high titers during the year of observation. Colostrum-derived antibodies to bovine viral diarrhea virus in nine calves declined at an expected rate for the first four to six months of age. However, titers of six of these calves increased at five to eight months of age and either remained constant or increased through one year of age. Bovine viral diarrhea virus antibody titers of the other three calves declined at a constant rate to less than 1:4 by nine to 12 months of age."}
{"id": "PMID:208739", "title": "Dissociation of cyclic GMP synthesis from cholinergic-stimulated secretion of protein from rat exocrine pancreas.", "content": "The phosphodiesterase inhibitors RO-201724/1 and 1-methyl-3-isobutylxanthine (MIX) stimulate a rapid increase in cyclic GMP content in rat pancreas; the latter agent also potentiates the stimulatory effect of carbachol on cyclic GMP synthesis. However, neither RO-201724/1 nor MIX alter basal secretion of 3H-labeled protein, nor do they affect the secretory response to carbachol used in either suboptimal or optimal concentrations. MIX as well does not alter the rate at which carbachol stimulates pancreatic enzyme release. The ability of carbachol to increase cyclic GMP synthesis is lost if extracellular calcium concentration is lowered to 0.05 mM; at this calcium concentration, however, the muscarinic agent still elicits a marked secretory effect. The dissociation between cyclic GMP synthesis and the secretory response suggests that the cyclic nucleotide does not play a major role in the stimulus--enzyme secretion coupling phenomenon of the exocrine pancreas.", "contents": "Dissociation of cyclic GMP synthesis from cholinergic-stimulated secretion of protein from rat exocrine pancreas. The phosphodiesterase inhibitors RO-201724/1 and 1-methyl-3-isobutylxanthine (MIX) stimulate a rapid increase in cyclic GMP content in rat pancreas; the latter agent also potentiates the stimulatory effect of carbachol on cyclic GMP synthesis. However, neither RO-201724/1 nor MIX alter basal secretion of 3H-labeled protein, nor do they affect the secretory response to carbachol used in either suboptimal or optimal concentrations. MIX as well does not alter the rate at which carbachol stimulates pancreatic enzyme release. The ability of carbachol to increase cyclic GMP synthesis is lost if extracellular calcium concentration is lowered to 0.05 mM; at this calcium concentration, however, the muscarinic agent still elicits a marked secretory effect. The dissociation between cyclic GMP synthesis and the secretory response suggests that the cyclic nucleotide does not play a major role in the stimulus--enzyme secretion coupling phenomenon of the exocrine pancreas."}
{"id": "PMID:208740", "title": "Validation of a single-compartment approach to the calculation of secretion rates of ACTH.", "content": "A single-compartment model used in this laboratory for continuously calculating ACTH secretion rates from measured plasma ACTH concentrations has been tested for its ability to follow changing rates of ACTH entry (rapid departure from steady state). ACTH was infused at known moderately high but physiological rates into anaesthetized dogs (Nembutal). Under such conditions endogenous secretion is initially less than 5% of infused rates. Orthogonal polynomials (ACTHt) were fitted to plasma ACTH vs. time data. Then secretion ratet = (ACTHt X MCR) + (dACTHt/dt X V) where it was previously shown that the metabolic clearance rate of ACTH (MCR) lacked significant inter-animal or concentration-dependent variation, and its distribution volume (V) was also constant. The calculated ACTH entry rate curves (a) followed a 10-fold increase in infusion rate over 4 min and subsequent rapid decline with a lag of only about 1 min and, despite some blurring, gave an integrated response equal to 94 +/- 5.5% of the known signal, and (b) followed a sinusoidal change in infusion rate (amplitude, 1.7 X base rate; period, 40 min) with a few percent error and negligible lag. These signals imitate (a) an abrupt stress response, and (b) other rapid departures from steady state.", "contents": "Validation of a single-compartment approach to the calculation of secretion rates of ACTH. A single-compartment model used in this laboratory for continuously calculating ACTH secretion rates from measured plasma ACTH concentrations has been tested for its ability to follow changing rates of ACTH entry (rapid departure from steady state). ACTH was infused at known moderately high but physiological rates into anaesthetized dogs (Nembutal). Under such conditions endogenous secretion is initially less than 5% of infused rates. Orthogonal polynomials (ACTHt) were fitted to plasma ACTH vs. time data. Then secretion ratet = (ACTHt X MCR) + (dACTHt/dt X V) where it was previously shown that the metabolic clearance rate of ACTH (MCR) lacked significant inter-animal or concentration-dependent variation, and its distribution volume (V) was also constant. The calculated ACTH entry rate curves (a) followed a 10-fold increase in infusion rate over 4 min and subsequent rapid decline with a lag of only about 1 min and, despite some blurring, gave an integrated response equal to 94 +/- 5.5% of the known signal, and (b) followed a sinusoidal change in infusion rate (amplitude, 1.7 X base rate; period, 40 min) with a few percent error and negligible lag. These signals imitate (a) an abrupt stress response, and (b) other rapid departures from steady state."}
{"id": "PMID:208741", "title": "Mediation of isoproterenol-induced thirst in rats by beta2-adrenergic receptors.", "content": "Isoproterenol-induced thirst in rats has been attributed to the activation of beta-adrenergic receptors. Since these receptors can be further differentiated pharmacologically into beta1 and beta2 types, experiments were performed using several beta-adrenergic agonists and antagonists to determine the receptor type initiating the isoproterenol-induced thirst. The beta1- and beta2-adrenergic antagonist, d,l-propranolol (1 mg/kg, ip), blocked the increase in water intake usually accompanying acute subcutaneous administration of isoproterenol (25 microgram/kg) to female rats. Since l-propranolol is known to stabilize membranes and to possess anesthetic-like properties, d-propranolol was also used. This isomer has little beta-adrenergic-blocking activity but possesses anesthetic-like activity. Administration of d-propranolol (1 mg/kg, ip) failed to affect the drinking response to acute administration of isoproterenol (25 microgram/kg). Practolol (125 mg/kg), a beta1-adrenergic antagonist with little anesthetic properties, also had no effect on water intake of isoproterenol-treated rats. Butoxamine, a selective beta2-adrenergic antagonist, attenuated the drinking response to isoproterenol. Salbutamol (150 microgram/kg), a beta2-adrenergic agonist, mimicked the effect of isoproterenol on water intake. These results are consistent with the suggestion that beta2-adrenergic receptors mediate the isoproterenol-induced thirst in rats.", "contents": "Mediation of isoproterenol-induced thirst in rats by beta2-adrenergic receptors. Isoproterenol-induced thirst in rats has been attributed to the activation of beta-adrenergic receptors. Since these receptors can be further differentiated pharmacologically into beta1 and beta2 types, experiments were performed using several beta-adrenergic agonists and antagonists to determine the receptor type initiating the isoproterenol-induced thirst. The beta1- and beta2-adrenergic antagonist, d,l-propranolol (1 mg/kg, ip), blocked the increase in water intake usually accompanying acute subcutaneous administration of isoproterenol (25 microgram/kg) to female rats. Since l-propranolol is known to stabilize membranes and to possess anesthetic-like properties, d-propranolol was also used. This isomer has little beta-adrenergic-blocking activity but possesses anesthetic-like activity. Administration of d-propranolol (1 mg/kg, ip) failed to affect the drinking response to acute administration of isoproterenol (25 microgram/kg). Practolol (125 mg/kg), a beta1-adrenergic antagonist with little anesthetic properties, also had no effect on water intake of isoproterenol-treated rats. Butoxamine, a selective beta2-adrenergic antagonist, attenuated the drinking response to isoproterenol. Salbutamol (150 microgram/kg), a beta2-adrenergic agonist, mimicked the effect of isoproterenol on water intake. These results are consistent with the suggestion that beta2-adrenergic receptors mediate the isoproterenol-induced thirst in rats."}
{"id": "PMID:208742", "title": "An investigation of the activity of opiate drug receptors located on frog skeletal muscle fibre membrane.", "content": "Extracellular and intracellular microelectrode studies were conducted to test the actions and interactions of opiate agonists, antagonists, and procaine on action potentials in frog sartorius muscles. Extracellular studies showed that morphine, methadone, propoxyphene, and procaine all depressed action potential production. Low concentrations of naloxone or naltrexone antagonized the excitability depression produced by the three opiate agonists but not the depression produced by procaine. Intracellular studies revealed that certain concentrations of the opiate agonists produced a biphasic decline in the stimulus-induced increase in sodium conductance (gNa). Naloxone or naltrexone antagonized only the second phase of this decline. These results show that part of the excitability depression produced by opiate agonists is due to an action on opiate drug receptors.", "contents": "An investigation of the activity of opiate drug receptors located on frog skeletal muscle fibre membrane. Extracellular and intracellular microelectrode studies were conducted to test the actions and interactions of opiate agonists, antagonists, and procaine on action potentials in frog sartorius muscles. Extracellular studies showed that morphine, methadone, propoxyphene, and procaine all depressed action potential production. Low concentrations of naloxone or naltrexone antagonized the excitability depression produced by the three opiate agonists but not the depression produced by procaine. Intracellular studies revealed that certain concentrations of the opiate agonists produced a biphasic decline in the stimulus-induced increase in sodium conductance (gNa). Naloxone or naltrexone antagonized only the second phase of this decline. These results show that part of the excitability depression produced by opiate agonists is due to an action on opiate drug receptors."}
{"id": "PMID:208743", "title": "Effect of estrogens on apomorphine-induced circling behavior in the rat.", "content": "The effect of administration of estrogens parenterally for 1 week was tested on apomorphine-induced circling in a group of castrated female rats with a lesion of the left entopednucluar nucleus. We observed a significant decrease in the number of turns per minute in estrogen-treated animals as compared with controls. Our tentative explanation is that estrogens decrease the sensitivity of dopamine receptors in the striatum.", "contents": "Effect of estrogens on apomorphine-induced circling behavior in the rat. The effect of administration of estrogens parenterally for 1 week was tested on apomorphine-induced circling in a group of castrated female rats with a lesion of the left entopednucluar nucleus. We observed a significant decrease in the number of turns per minute in estrogen-treated animals as compared with controls. Our tentative explanation is that estrogens decrease the sensitivity of dopamine receptors in the striatum."}
{"id": "PMID:208744", "title": "Multiple sclerosis treated with antithymocyte globulin--a five year follow-up.", "content": "Multiple sclerosis patients treated with antithymocyte globulin (ATG) were re-evaluated after five years. No long term benefit was found. Notably, the group of patients with an elevated gamma globulin to total protein ration in their C.S.F. and who did particularly well after treatment with ATG also failed to show any long term benefit. Few long term detrimental effects of ATG immunosuppression were identified. The implications of the results are discussed as they relate to the use of immunosuppression in multiple sclerosis.", "contents": "Multiple sclerosis treated with antithymocyte globulin--a five year follow-up. Multiple sclerosis patients treated with antithymocyte globulin (ATG) were re-evaluated after five years. No long term benefit was found. Notably, the group of patients with an elevated gamma globulin to total protein ration in their C.S.F. and who did particularly well after treatment with ATG also failed to show any long term benefit. Few long term detrimental effects of ATG immunosuppression were identified. The implications of the results are discussed as they relate to the use of immunosuppression in multiple sclerosis."}
{"id": "PMID:208745", "title": "The role of radiation therapy in the treatment of glomus jugulare tumors.", "content": "The records of 14 patients who received irradiation for incompletely excised, inoperable or recurrent glomus jugulare tumors were retrospectively reviewed. Ages ranged from 12 to 66 years, and the male to female ratio was 1:3. With a follow-up time of 1.3 to 17.2 years (mean of 7.7 years), 11/14 remain clinically disease-free. Doses of at least 4000 rad are shown to be effective in controlling glomus jugular tumors.", "contents": "The role of radiation therapy in the treatment of glomus jugulare tumors. The records of 14 patients who received irradiation for incompletely excised, inoperable or recurrent glomus jugulare tumors were retrospectively reviewed. Ages ranged from 12 to 66 years, and the male to female ratio was 1:3. With a follow-up time of 1.3 to 17.2 years (mean of 7.7 years), 11/14 remain clinically disease-free. Doses of at least 4000 rad are shown to be effective in controlling glomus jugular tumors."}
{"id": "PMID:208746", "title": "Postirradiation sarcoma (malignant fibrous histiocytoma) of axilla.", "content": "A case is reported of a patient who developed a histologically unusual sarcoma in the axilla and chest wall 8 years after receiving radiation therapy (6500 rad) for carcinoma of the breast. This sarcoma showed light- and electron-microscopic features of a malignant fibrous histiocytoma, a tumor not documented among 24 previously reported cases of postirradiation sarcoma following the diagnosis of breast carcinoma. In addition, the literature is reviewed and discussed regarding postirradiation sarcoma in general following breast carcinoma.", "contents": "Postirradiation sarcoma (malignant fibrous histiocytoma) of axilla. A case is reported of a patient who developed a histologically unusual sarcoma in the axilla and chest wall 8 years after receiving radiation therapy (6500 rad) for carcinoma of the breast. This sarcoma showed light- and electron-microscopic features of a malignant fibrous histiocytoma, a tumor not documented among 24 previously reported cases of postirradiation sarcoma following the diagnosis of breast carcinoma. In addition, the literature is reviewed and discussed regarding postirradiation sarcoma in general following breast carcinoma."}
{"id": "PMID:208747", "title": "Cell-mediated immunity to varicella zoster virus in children being treated for cancer.", "content": "Stimulation of lymphocytes by varicella-zoster virus (VZV) antigen was measured in vitro for 37 healthy adults and children and for 35 children who developed herpes zoster or varicella while receiving anticancer therapy. For 35 of the control group the history of varicella infection correlated with the in vitro response of lymphocytes to VZV antigen. A specific lymphocyte response was observed following 32 of the 37 episodes of VZV infection in the 35 children with malignancy. Re-evaluation 7--12 months following the acute infection revealed that the in vitro response to VZV antigen was lost in six of 19 patients who remained in remission and in all patients who relapsed and received reinduction therapy. Although there was some suggestion that development of a cell mediated response early in the infection decreased the incidence of skin dissemination of the virus in herpes zoster, no consistent correlation could be made between lymphocyte responsiveness in vitro and dissemination of disease or the duration of the appearance of new lesions.", "contents": "Cell-mediated immunity to varicella zoster virus in children being treated for cancer. Stimulation of lymphocytes by varicella-zoster virus (VZV) antigen was measured in vitro for 37 healthy adults and children and for 35 children who developed herpes zoster or varicella while receiving anticancer therapy. For 35 of the control group the history of varicella infection correlated with the in vitro response of lymphocytes to VZV antigen. A specific lymphocyte response was observed following 32 of the 37 episodes of VZV infection in the 35 children with malignancy. Re-evaluation 7--12 months following the acute infection revealed that the in vitro response to VZV antigen was lost in six of 19 patients who remained in remission and in all patients who relapsed and received reinduction therapy. Although there was some suggestion that development of a cell mediated response early in the infection decreased the incidence of skin dissemination of the virus in herpes zoster, no consistent correlation could be made between lymphocyte responsiveness in vitro and dissemination of disease or the duration of the appearance of new lesions."}
{"id": "PMID:208748", "title": "Ultrastructure of primitive neuroectodermal neoplasms of the central nervous system.", "content": "The ultrastructure of one spinal and five cerebral neoplasms diagnosed by light microscopy as primitive neuroectodermal tumors supports a cell population consisting largely of poorly differentiated neuroepithelial cells. The most unique ultrastructure feature was the presence of annulate lamellae in four of the six cases. Glial cells in the neoplasm were not unequivocally of neoplastic origin and were possible reactive. There was no evidence of neuroblastic or neuronal elements, although there was frequently focal early neuroblastic differentiation by light microscopy. Although we have seen neoplasms which are clearly neuroblastic, these particular tumors are not purely neuroblastic and should not be classified as neuroblastomas.", "contents": "Ultrastructure of primitive neuroectodermal neoplasms of the central nervous system. The ultrastructure of one spinal and five cerebral neoplasms diagnosed by light microscopy as primitive neuroectodermal tumors supports a cell population consisting largely of poorly differentiated neuroepithelial cells. The most unique ultrastructure feature was the presence of annulate lamellae in four of the six cases. Glial cells in the neoplasm were not unequivocally of neoplastic origin and were possible reactive. There was no evidence of neuroblastic or neuronal elements, although there was frequently focal early neuroblastic differentiation by light microscopy. Although we have seen neoplasms which are clearly neuroblastic, these particular tumors are not purely neuroblastic and should not be classified as neuroblastomas."}
{"id": "PMID:208749", "title": "Glycosaminoglycan-synthetic activity of pleomorphic adenoma. Adenoid cystic carcinoma and nonneoplastic tubuloacinar cells of the salivary gland.", "content": "An analysis was carried out on glycosaminoglycan produced in pleomorphic adenoma, adenoid cystic carcinoma, sialadenitis and normal tissue of the salivary gland. After incubation of the tissue segments in a medium containing 35SO4, a radioautograph of the tissue section was made to observe the localization of 35SO4 incorporation, and 35S-labelled materials were purified from the tissues, and analyzed. High 35S-radioactivity was observed in the ductal cells of the inflammatory gland tissue and in the acinar cells of normal palatinal gland, but little radioactivity was observed in the interstitial components in these tissues, and the amount of 35SO4 incorporated in the tumor cells was also significant. Eighty to 90% of the 35S-radioactivity incorporated could be detected as 35S-glycosaminoglycans in all tissues except for the normal palatinal gland, which contained a large amount of 35S-sulfated glycoprotein. No significant difference in the synthetic activity of 35S-glycosaminoglycans and in their components were observed between nonneoplastic and neoplastic cells. These results suggest that glycosaminoglycan-producing cells in pleomorphic adenoma as well as in adenoid cystic carcinoma are derived from the tubuloacinar cells of the salivary gland.", "contents": "Glycosaminoglycan-synthetic activity of pleomorphic adenoma. Adenoid cystic carcinoma and nonneoplastic tubuloacinar cells of the salivary gland. An analysis was carried out on glycosaminoglycan produced in pleomorphic adenoma, adenoid cystic carcinoma, sialadenitis and normal tissue of the salivary gland. After incubation of the tissue segments in a medium containing 35SO4, a radioautograph of the tissue section was made to observe the localization of 35SO4 incorporation, and 35S-labelled materials were purified from the tissues, and analyzed. High 35S-radioactivity was observed in the ductal cells of the inflammatory gland tissue and in the acinar cells of normal palatinal gland, but little radioactivity was observed in the interstitial components in these tissues, and the amount of 35SO4 incorporated in the tumor cells was also significant. Eighty to 90% of the 35S-radioactivity incorporated could be detected as 35S-glycosaminoglycans in all tissues except for the normal palatinal gland, which contained a large amount of 35S-sulfated glycoprotein. No significant difference in the synthetic activity of 35S-glycosaminoglycans and in their components were observed between nonneoplastic and neoplastic cells. These results suggest that glycosaminoglycan-producing cells in pleomorphic adenoma as well as in adenoid cystic carcinoma are derived from the tubuloacinar cells of the salivary gland."}
{"id": "PMID:208750", "title": "Malignant mixed tumor of the vagina probably arising in mesonephric rests.", "content": "An exceedingly rare tumor arising in the upper lateral vagina is described histologically, histochemically, and ultrastructurally. It is compared to the lesion reported by Okagaki et al. which is considered to represent the same type of tumor. Comparison with synovial sarcomas indicates that the lesion is similar, but the reasons why it should not be so classified are discussed. Evidence is presented for the origin of these tumors in mesonephric rests (Gartner's duct).", "contents": "Malignant mixed tumor of the vagina probably arising in mesonephric rests. An exceedingly rare tumor arising in the upper lateral vagina is described histologically, histochemically, and ultrastructurally. It is compared to the lesion reported by Okagaki et al. which is considered to represent the same type of tumor. Comparison with synovial sarcomas indicates that the lesion is similar, but the reasons why it should not be so classified are discussed. Evidence is presented for the origin of these tumors in mesonephric rests (Gartner's duct)."}
{"id": "PMID:208751", "title": "Clear cell sarcoma of tendons and aponeuroses: a comparative study of 13 cases with a provisional subgrouping into the melanotic and synovial types.", "content": "Electron microscopy of two cases of clear cell sarcoma of tendons and aponeuroses showed different fine structures. On the basis of these differences a proposed division is made of melanotic and synovial types of the tumor. A subsequent comparative histological study carried out on these tumors showed that there were histological criteria to separate the melanotic and synovial types of sarcoma. Using these histological criteria eleven further cases of clear cell sarcoma in the files of the Tumor Registry were subdivided. Review of the Tumor Registry material showed that eight were melanotic type tumors and one was a further synovial type tumor. Using these histological criteria there are two further cases in the Tumor Registry which are not clearly classifiable into either group. The present observations indicate that the majority of the so-called clear cell sarcomas are in reality \"melanomas of soft parts\" with a minority of this type of tumor being of \"synovial type\".", "contents": "Clear cell sarcoma of tendons and aponeuroses: a comparative study of 13 cases with a provisional subgrouping into the melanotic and synovial types. Electron microscopy of two cases of clear cell sarcoma of tendons and aponeuroses showed different fine structures. On the basis of these differences a proposed division is made of melanotic and synovial types of the tumor. A subsequent comparative histological study carried out on these tumors showed that there were histological criteria to separate the melanotic and synovial types of sarcoma. Using these histological criteria eleven further cases of clear cell sarcoma in the files of the Tumor Registry were subdivided. Review of the Tumor Registry material showed that eight were melanotic type tumors and one was a further synovial type tumor. Using these histological criteria there are two further cases in the Tumor Registry which are not clearly classifiable into either group. The present observations indicate that the majority of the so-called clear cell sarcomas are in reality \"melanomas of soft parts\" with a minority of this type of tumor being of \"synovial type\"."}
{"id": "PMID:208753", "title": "Association of carcinoma of the breast with adenosquamous carcinoma of endometrium.", "content": "Numerous investigators have alluded to an association of cancer of the endometrium and breast. There is no available information relating the histologic forms of cancer of the endometrium to breast cancer. We found ten cases of adenosquamous carcinoma of the endometrium in one tumor registry in a ten year period, 1967-1977. Five of these cases also had breast carcinoma. In three of these cases the breast carcinoma was discovered two to three years after hysterectomy; in one case both tumors were discovered at the same time, and in one case the breast carcinoma antedated the diagnosis of endometrial malignancy by approximately one year. These observations, although from a small number of cases, warrant an expansion of this study in order to determine whether patients with adenosquamous carcinoma of the uterus have a higher risk of developing breast cancer.", "contents": "Association of carcinoma of the breast with adenosquamous carcinoma of endometrium. Numerous investigators have alluded to an association of cancer of the endometrium and breast. There is no available information relating the histologic forms of cancer of the endometrium to breast cancer. We found ten cases of adenosquamous carcinoma of the endometrium in one tumor registry in a ten year period, 1967-1977. Five of these cases also had breast carcinoma. In three of these cases the breast carcinoma was discovered two to three years after hysterectomy; in one case both tumors were discovered at the same time, and in one case the breast carcinoma antedated the diagnosis of endometrial malignancy by approximately one year. These observations, although from a small number of cases, warrant an expansion of this study in order to determine whether patients with adenosquamous carcinoma of the uterus have a higher risk of developing breast cancer."}
{"id": "PMID:208754", "title": "Undifferentiated (embryonal) sarcoma of the liver: report of 31 cases.", "content": "Thirty-one cases of undifferentiated (embryonal) sarcoma of the liver are presented. The tumor is found predominantly in the pediatric age group, the majority of patients (51.6%) being between 6 and 10 years of age. An abdominal mass and pain are the usual presenting symptoms. Radiographic examination is nonspecific except to demonstrate a space-occupying lesion of the liver. The tumors are large, single, usually globular and well demarcated, and have multiple cystic areas of hemorrhage, necrosis, and gelatinous degeneration. Histologic examination shows a pseudocapsule partially separating the normal liver from undifferentiated sarcomatous cells that, near the periphery of the tumor, surround entrapped hyperplastic or degenerating bile duct-like structures. Eosinophilic globules that are PAS positive are usually found within and adjacent to tumor cells. Areas of necrosis and hemorrhage are prominent. The prognosis is poor, with a median survival of less than 1 year following diagnosis.", "contents": "Undifferentiated (embryonal) sarcoma of the liver: report of 31 cases. Thirty-one cases of undifferentiated (embryonal) sarcoma of the liver are presented. The tumor is found predominantly in the pediatric age group, the majority of patients (51.6%) being between 6 and 10 years of age. An abdominal mass and pain are the usual presenting symptoms. Radiographic examination is nonspecific except to demonstrate a space-occupying lesion of the liver. The tumors are large, single, usually globular and well demarcated, and have multiple cystic areas of hemorrhage, necrosis, and gelatinous degeneration. Histologic examination shows a pseudocapsule partially separating the normal liver from undifferentiated sarcomatous cells that, near the periphery of the tumor, surround entrapped hyperplastic or degenerating bile duct-like structures. Eosinophilic globules that are PAS positive are usually found within and adjacent to tumor cells. Areas of necrosis and hemorrhage are prominent. The prognosis is poor, with a median survival of less than 1 year following diagnosis."}
{"id": "PMID:208755", "title": "Chemoimmunotherapy of small cell bronchogenic carcinoma.", "content": "Thirty-one patients with small cell bronchogenic carcinoma were treated with a regimen of cyclophosphamide, Adriamycin and vincristine. Radiotherapy was given to patients with limited disease. Nonspecific immunotherapy consisting of BCG scarification was administered after each chemotherapy course. The results of treatment for this group were compared with those for a group of 45 patients treated similarly but with no immunotherapy. Therapeutic results, expressed in length of survival and rate of response, were similar. Myelosuppression was not modified by the addition of BCG scarification. This study showed no benefit from the use of such nonspecific immunotherapy.", "contents": "Chemoimmunotherapy of small cell bronchogenic carcinoma. Thirty-one patients with small cell bronchogenic carcinoma were treated with a regimen of cyclophosphamide, Adriamycin and vincristine. Radiotherapy was given to patients with limited disease. Nonspecific immunotherapy consisting of BCG scarification was administered after each chemotherapy course. The results of treatment for this group were compared with those for a group of 45 patients treated similarly but with no immunotherapy. Therapeutic results, expressed in length of survival and rate of response, were similar. Myelosuppression was not modified by the addition of BCG scarification. This study showed no benefit from the use of such nonspecific immunotherapy."}
{"id": "PMID:208756", "title": "Chylous ascites following retroperitoneal lymphadenectomy: report of 2 cases with guidelines for diagnosis and treatment.", "content": "Two cases of chylous ascites following retroperitoneal lymphadenectomy are presented. The first case, a 3-year-old girl, undersent a right radical nephrectomy and retroperitoneal lymph node dissection for Wilms' tumor. Chylous ascites developed postoperatively and resolved after 3 months of supportive therapy. The second case, a 45-year-old woman, underwent a right radical nephrectomy and retroperitoneal lymph node dissection for renal carcinoma. Chylous ascites occurred postoperatively and resolved after a single paracentesis. Diagnosis, evaluation, and therapeutic modalities are outlined and the literature is reviewed.", "contents": "Chylous ascites following retroperitoneal lymphadenectomy: report of 2 cases with guidelines for diagnosis and treatment. Two cases of chylous ascites following retroperitoneal lymphadenectomy are presented. The first case, a 3-year-old girl, undersent a right radical nephrectomy and retroperitoneal lymph node dissection for Wilms' tumor. Chylous ascites developed postoperatively and resolved after 3 months of supportive therapy. The second case, a 45-year-old woman, underwent a right radical nephrectomy and retroperitoneal lymph node dissection for renal carcinoma. Chylous ascites occurred postoperatively and resolved after a single paracentesis. Diagnosis, evaluation, and therapeutic modalities are outlined and the literature is reviewed."}
{"id": "PMID:208757", "title": "Complete necrotization of hepatocellular carcinoma by chemotherapy and subsequent intravascular coagulation: a case report.", "content": "A 45-year-old man with hepatocellular carcinoma who developed intravascular coagulation following complete tumor regression by chemotherapy is described. After 2 doses of 10 mg of Mitomycin C given into the hepatic artery at the time of selective angiography, and 16 intravenous doses of 5-fluorouracil and Mitomycin C, 2 doses per week, subjective symptoms and hepatomegaly disappeared. Alpha-fetoprotein became negative and a remarkable change in tumor size and vasculature was noted in the arteriogram. Three months after chemotherapy, the patient developed thrombocytopenia, intravascular hemolysis, and acute renal failure. Autopsy disclosed a 8 X 7 X 5 cm solitary, encapsulated hepatocellular carcinoma in the right lobe. The tumor was surrounded by a thick capsule and completely necrotized. Neither intrahepatic invasion nor extrahepatic metastasis was observed. In the kidney, generalized fibrin thrombi were seen in the afferent arterioles of glomeruli as accounted for by intravascular coagulation.", "contents": "Complete necrotization of hepatocellular carcinoma by chemotherapy and subsequent intravascular coagulation: a case report. A 45-year-old man with hepatocellular carcinoma who developed intravascular coagulation following complete tumor regression by chemotherapy is described. After 2 doses of 10 mg of Mitomycin C given into the hepatic artery at the time of selective angiography, and 16 intravenous doses of 5-fluorouracil and Mitomycin C, 2 doses per week, subjective symptoms and hepatomegaly disappeared. Alpha-fetoprotein became negative and a remarkable change in tumor size and vasculature was noted in the arteriogram. Three months after chemotherapy, the patient developed thrombocytopenia, intravascular hemolysis, and acute renal failure. Autopsy disclosed a 8 X 7 X 5 cm solitary, encapsulated hepatocellular carcinoma in the right lobe. The tumor was surrounded by a thick capsule and completely necrotized. Neither intrahepatic invasion nor extrahepatic metastasis was observed. In the kidney, generalized fibrin thrombi were seen in the afferent arterioles of glomeruli as accounted for by intravascular coagulation."}
{"id": "PMID:208758", "title": "Oat cell carcinoma of the larynx: response to combined modality therapy.", "content": "A patient with oat cell carcinoma of the larynx with metastasis to cervical lymph nodes is presented. Treatment with radiation and chemotherapy has achieved a sustained remission. Pretherapy staging and combined modality therapy are discussed.", "contents": "Oat cell carcinoma of the larynx: response to combined modality therapy. A patient with oat cell carcinoma of the larynx with metastasis to cervical lymph nodes is presented. Treatment with radiation and chemotherapy has achieved a sustained remission. Pretherapy staging and combined modality therapy are discussed."}
{"id": "PMID:208759", "title": "Cyclic nucleotide concentrations in 1,2-dimethylhydrazine and x-ray induced rat small intestinal cancer.", "content": "The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) were determined in adult male Holtzman rat small intestinal tumors induced by subcutaneous administration of 1,2-dimethylhydrazine (DMH) or X-irradiation of only the hypoxic ileum and jejunum. The levels of cAMP and cGMP in the cancer cells from DMH-treated animals were 50% and 200%, respectively, of the values measured for intestinal tissue. The amounts of cGMP in the lesion of the X-irradiation induced rat small bowel adenocarcinoma determined in the present investigation and of cAMP measured previously were observed to be only 50% of the value for unirradiated intestine. It has thus been shown that in the DMH-induced colon and small intestinal tumors, the X-irradiation induced rat small bowel adenocarcinoma and the human colon adenocarcinoma, the cAMP concentrations are consistently about 50% of the levels measured in comparable normal tissues. These findings of diminished intracellular cAMP concentrations imply a serious cellular defect mechanism occurring in intestinal cancer. However, there appears to be no similar pattern of change for the intracellular concentrations of cGMP, which suggests that different biochemical pathways exist in these malignancies.", "contents": "Cyclic nucleotide concentrations in 1,2-dimethylhydrazine and x-ray induced rat small intestinal cancer. The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) were determined in adult male Holtzman rat small intestinal tumors induced by subcutaneous administration of 1,2-dimethylhydrazine (DMH) or X-irradiation of only the hypoxic ileum and jejunum. The levels of cAMP and cGMP in the cancer cells from DMH-treated animals were 50% and 200%, respectively, of the values measured for intestinal tissue. The amounts of cGMP in the lesion of the X-irradiation induced rat small bowel adenocarcinoma determined in the present investigation and of cAMP measured previously were observed to be only 50% of the value for unirradiated intestine. It has thus been shown that in the DMH-induced colon and small intestinal tumors, the X-irradiation induced rat small bowel adenocarcinoma and the human colon adenocarcinoma, the cAMP concentrations are consistently about 50% of the levels measured in comparable normal tissues. These findings of diminished intracellular cAMP concentrations imply a serious cellular defect mechanism occurring in intestinal cancer. However, there appears to be no similar pattern of change for the intracellular concentrations of cGMP, which suggests that different biochemical pathways exist in these malignancies."}
{"id": "PMID:208761", "title": "Oncogenicity of purine 3-oxide and unsubstituted purine in rats.", "content": "Injection s.c. of purine 3-oxide into Wistar rats resulted in the appearance of sarcomas and fibromas at the interscapular site of administration, carcinomas in the liver, and a high incidence of s.c. fibromas in the hip at a distance from the site of injection. A small number of liver tumors but not tumors at the injection site appeared in rats to which the parent compound, purine, was administered. Oxidation of purine 3-oxide by xanthine oxidase was found to occur in two steps to yield the potent oncogen 3-hydroxyxanthine. A similar process may occur in vivo since a protein preparation from rat s.c. tissue has similar oxidizing activity.", "contents": "Oncogenicity of purine 3-oxide and unsubstituted purine in rats. Injection s.c. of purine 3-oxide into Wistar rats resulted in the appearance of sarcomas and fibromas at the interscapular site of administration, carcinomas in the liver, and a high incidence of s.c. fibromas in the hip at a distance from the site of injection. A small number of liver tumors but not tumors at the injection site appeared in rats to which the parent compound, purine, was administered. Oxidation of purine 3-oxide by xanthine oxidase was found to occur in two steps to yield the potent oncogen 3-hydroxyxanthine. A similar process may occur in vivo since a protein preparation from rat s.c. tissue has similar oxidizing activity."}
{"id": "PMID:208763", "title": "Effect of structure on tumor specificity of alicyclic alpha-amino acids.", "content": "The selective affinity of [carboxyl-11C]-1-aminocyclopentanecarboxylic acid (ACPC) for tumor tissue has led us to study the tumor-localizing characteristics of a series of alicyclic alpha-amino acid analogs of ACPC. The tissue distributions of [14C]-1-aminocyclopropanecarboxylic acid, 1-aminocyclobutanecarboxylic acid (ACBC), 1-aminocyclohexanecarboxylic acid, 1-amino-2-methylcyclopentanecarboxylic acid were compared with that of ACPC in Buffalo rats bearing Morris 5123C hepatomas. ACPC and ACBC were found to have significantly higher tumor-to-nontumor concentration ratios than the other four amino acids. ACBC generally had higher tumor-to-nontumor ratios than did ACPC, significantly so for muscle, kidney, and testis and marginally so for blood. These results suggest that [carboxyl-11C]ACBC may be a better agent than [carboxyl-11C]ACPC for tumor imaging by positron tomography.", "contents": "Effect of structure on tumor specificity of alicyclic alpha-amino acids. The selective affinity of [carboxyl-11C]-1-aminocyclopentanecarboxylic acid (ACPC) for tumor tissue has led us to study the tumor-localizing characteristics of a series of alicyclic alpha-amino acid analogs of ACPC. The tissue distributions of [14C]-1-aminocyclopropanecarboxylic acid, 1-aminocyclobutanecarboxylic acid (ACBC), 1-aminocyclohexanecarboxylic acid, 1-amino-2-methylcyclopentanecarboxylic acid were compared with that of ACPC in Buffalo rats bearing Morris 5123C hepatomas. ACPC and ACBC were found to have significantly higher tumor-to-nontumor concentration ratios than the other four amino acids. ACBC generally had higher tumor-to-nontumor ratios than did ACPC, significantly so for muscle, kidney, and testis and marginally so for blood. These results suggest that [carboxyl-11C]ACBC may be a better agent than [carboxyl-11C]ACPC for tumor imaging by positron tomography."}
{"id": "PMID:208766", "title": "Growth retardation and prevention of Ehrlich solid tumor by Clostridium perfringens type A spores and culture supernatant.", "content": "When given by direct s.c. injection into the Ehrlich solid carcinoma 1 week after s.c. tumor transfer, viable crude spores of Clostridium perfringens type A (attenuated mutant strain LNG11 ATCC 29348) inhibited tumor growth and significantly prolonged the life span of male outbred Swiss mice. Under these conditions a concentrated sterile supernatant of a C. perfringens culture proved to be slightly more effective than were viable crude spores. In contrast viable crude spores were ineffective in the treatment of female Swiss mice, but the sterile supernatant retained significant activity. When given at the time and site of s.c. grafting of Ehrlich tumor cells, a concentrated sterile supernatant of a C. perfringens culture prevented tumor growth in 80% of male outbred Swiss mice. Under these conditions viable crude spores prevented tumor growth in 70% of mice and significantly prolonged the life span in the other 30%. When given by i.p. injection and before i.p. grafting of tumor cells, viable crude spores of C. perfringens prevented Ehrlich ascites tumor in 5 of 12 Swiss mice and prolonged life span in the other 7. In contrast concentrated sterile supernatant and viable purified spores were ineffective in the prevention or delay of the growth of Ehrlich ascites tumor. These data indicate that C. perfringens can be a potent antitumor agent without producing the harmful anaerobic infection of solid tumors (clostridial oncolysis.", "contents": "Growth retardation and prevention of Ehrlich solid tumor by Clostridium perfringens type A spores and culture supernatant. When given by direct s.c. injection into the Ehrlich solid carcinoma 1 week after s.c. tumor transfer, viable crude spores of Clostridium perfringens type A (attenuated mutant strain LNG11 ATCC 29348) inhibited tumor growth and significantly prolonged the life span of male outbred Swiss mice. Under these conditions a concentrated sterile supernatant of a C. perfringens culture proved to be slightly more effective than were viable crude spores. In contrast viable crude spores were ineffective in the treatment of female Swiss mice, but the sterile supernatant retained significant activity. When given at the time and site of s.c. grafting of Ehrlich tumor cells, a concentrated sterile supernatant of a C. perfringens culture prevented tumor growth in 80% of male outbred Swiss mice. Under these conditions viable crude spores prevented tumor growth in 70% of mice and significantly prolonged the life span in the other 30%. When given by i.p. injection and before i.p. grafting of tumor cells, viable crude spores of C. perfringens prevented Ehrlich ascites tumor in 5 of 12 Swiss mice and prolonged life span in the other 7. In contrast concentrated sterile supernatant and viable purified spores were ineffective in the prevention or delay of the growth of Ehrlich ascites tumor. These data indicate that C. perfringens can be a potent antitumor agent without producing the harmful anaerobic infection of solid tumors (clostridial oncolysis."}
{"id": "PMID:208767", "title": "Mammary tumor virus oncogenesis and tumor immunogenicity in three sublines of the C3H mouse.", "content": "Mammary tumorigenesis and mammary tumor transplantation immunogenicity have been studied and compared in three sublines of the C3H strain: in standard mammary tumor virus (MTV-S)-infected C3H/He mice; in MTV-S-infected C3H/Ki mice; and in MTV-S-free C3Hf/He mice. The age at the appearance of the first tumor, the growth rate of the tumors in their first transplant generation, and the immunogenicity of each tumor in syngeneic female recipients have been determined for the first tumor to appear in each of 25 breeding females from each of the three sublines. Two statistically significant trends were evident among the tumor characteristics compared in the three sublines: (a) an early appearance of tumors was related to the presence of the MTV-S. The genetically dissimilar sublines, C3H/He and C3H/Ki, both infected with the MTV-S, developed mammary tumors at an average age of about 10 months, 11 months before MTV-S-free C3Hf/He mice; (b) the tumor characteristics of immunogenicity and growth stimulation were related to host genetic factors. The genetically similar sublines, C3H/He and C3Hf/He, developed similar proportions of immunogenic and growth-stimulating mammary tumors; the genetically divergent C3H/Ki subline developed tumors that were not immunogenic and tended to be strongly growth stimulating.", "contents": "Mammary tumor virus oncogenesis and tumor immunogenicity in three sublines of the C3H mouse. Mammary tumorigenesis and mammary tumor transplantation immunogenicity have been studied and compared in three sublines of the C3H strain: in standard mammary tumor virus (MTV-S)-infected C3H/He mice; in MTV-S-infected C3H/Ki mice; and in MTV-S-free C3Hf/He mice. The age at the appearance of the first tumor, the growth rate of the tumors in their first transplant generation, and the immunogenicity of each tumor in syngeneic female recipients have been determined for the first tumor to appear in each of 25 breeding females from each of the three sublines. Two statistically significant trends were evident among the tumor characteristics compared in the three sublines: (a) an early appearance of tumors was related to the presence of the MTV-S. The genetically dissimilar sublines, C3H/He and C3H/Ki, both infected with the MTV-S, developed mammary tumors at an average age of about 10 months, 11 months before MTV-S-free C3Hf/He mice; (b) the tumor characteristics of immunogenicity and growth stimulation were related to host genetic factors. The genetically similar sublines, C3H/He and C3Hf/He, developed similar proportions of immunogenic and growth-stimulating mammary tumors; the genetically divergent C3H/Ki subline developed tumors that were not immunogenic and tended to be strongly growth stimulating."}
{"id": "PMID:208768", "title": "Observations on the question of horizontal transmission of mouse mammary tumor virus.", "content": "Antigen and tumor incidences in BALB/c and C57BL mice after living as weanlings for 5 weeks in cages with mouse mammary tumor virus-infected females were compared with control BALB/c and C57BL mice living in the same laboratory. All mice were bred continuously, and third-lactation milks were tested for mouse mammary tumor virus antigen by Ouchterlony microimmunodiffusion test. Mammary tumor incidences in the cagemates were not significantly different from those in the controls, although the antigen incidences were significantly greater. However, phosphate-buffered salt solution (0.02 M phosphate, pH 7.4; 0.15 M NaCl; and 0.1% bovine serum albumin) and sham-inoculated mice also had elevated antigen incidences. Repeat tests of milks at the fourth or fifth lactations indicated that more than 50% of those positive at the third became negative at later lactations.", "contents": "Observations on the question of horizontal transmission of mouse mammary tumor virus. Antigen and tumor incidences in BALB/c and C57BL mice after living as weanlings for 5 weeks in cages with mouse mammary tumor virus-infected females were compared with control BALB/c and C57BL mice living in the same laboratory. All mice were bred continuously, and third-lactation milks were tested for mouse mammary tumor virus antigen by Ouchterlony microimmunodiffusion test. Mammary tumor incidences in the cagemates were not significantly different from those in the controls, although the antigen incidences were significantly greater. However, phosphate-buffered salt solution (0.02 M phosphate, pH 7.4; 0.15 M NaCl; and 0.1% bovine serum albumin) and sham-inoculated mice also had elevated antigen incidences. Repeat tests of milks at the fourth or fifth lactations indicated that more than 50% of those positive at the third became negative at later lactations."}
{"id": "PMID:208770", "title": "Mutagenesis of Chinese hamster cells in vitro by combination treatments with methyl methanesulfonate and N-acetoxy-2-acetylaminofluorene.", "content": "Mutational synergism was examined in Chinese hamster V79 cells exposed to methyl methanesulfonate followed by N-acetoxy-2-acetylaminofluorene (AcAAF) at different time intervals. Treatment with 500 micron methyl methanesulfonate resulted in 95% survival of cloning ability and induced approximately 4 azaguanine-resistant mutants/10(5) survivors. Seven micron AcAAF produced 10 times as many mutants, and the survival was 7%. Lethal synergism was observed for methyl methanesulfonate treatments followed by 7 micron AcAAF, and the resulting lethality was unaffected by increasing the time interval between treatments from 1 to 48 hr. However, no significant changes in the mutant frequency from that induced by AcAAF alone were found for treatment intervals of 1 to 63 hr. This result contrasts with the 6-fold enhancement of the AcAAF-induced transformation of Syrian hamster embryo cells exposed to the same combination with a 48-hr interval between treatments, as previously reported (Chem.-Biol. Interactions, 9: 351-364, 1974). The difference in the response of these two cell types demonstrates the difficulties in attempting to extrapolate the known correlation between individual mutagen and carcinogen treatments to combination treatments, with different cell types for the two cellular responses.", "contents": "Mutagenesis of Chinese hamster cells in vitro by combination treatments with methyl methanesulfonate and N-acetoxy-2-acetylaminofluorene. Mutational synergism was examined in Chinese hamster V79 cells exposed to methyl methanesulfonate followed by N-acetoxy-2-acetylaminofluorene (AcAAF) at different time intervals. Treatment with 500 micron methyl methanesulfonate resulted in 95% survival of cloning ability and induced approximately 4 azaguanine-resistant mutants/10(5) survivors. Seven micron AcAAF produced 10 times as many mutants, and the survival was 7%. Lethal synergism was observed for methyl methanesulfonate treatments followed by 7 micron AcAAF, and the resulting lethality was unaffected by increasing the time interval between treatments from 1 to 48 hr. However, no significant changes in the mutant frequency from that induced by AcAAF alone were found for treatment intervals of 1 to 63 hr. This result contrasts with the 6-fold enhancement of the AcAAF-induced transformation of Syrian hamster embryo cells exposed to the same combination with a 48-hr interval between treatments, as previously reported (Chem.-Biol. Interactions, 9: 351-364, 1974). The difference in the response of these two cell types demonstrates the difficulties in attempting to extrapolate the known correlation between individual mutagen and carcinogen treatments to combination treatments, with different cell types for the two cellular responses."}
{"id": "PMID:208775", "title": "Separation and maturation of gonadotrophs from 2A8 clonal cells in vitro.", "content": "2A8 clonal cells derived from the epithlium of Rathke's pouch of fetal rats were cultured in growth medium supplemented with fresh rat serum, median-eminence extract and 1-thyroxine. Then, in order to isolate gonadotrophs, cyanogen bromide-activated Sepharose whichwas conjugated with LHRH (LHRH-Sepharose) was added to the culture medium. Fourteen days after incubation of 2A8 cells with LHRH-Sepharose, agranular and granular cells were rapidly bound to LHRH-Sepharose when fresh serum had previously been added in the medium. The cytoplasm of granular cells that were bound to LHRH-Sepharose contained spherical secretory granules (200-250 nm in diameter). These cells were similar in morphology to the FSH and LH gonadotrophs described by Kurosumi (1968). Moreover, many of them appeared as hypertrophied cells that resembled \"castration\" cells. These results demonstrate that LHRH conjugated to Sepharose can be used to separate gonadotrophs from other 2A8 cells, and it is suggested that the hypertrophy of some cells might be due to persistent stimulation by LHRH which is likely bound to receptors on the cell membrane.", "contents": "Separation and maturation of gonadotrophs from 2A8 clonal cells in vitro. 2A8 clonal cells derived from the epithlium of Rathke's pouch of fetal rats were cultured in growth medium supplemented with fresh rat serum, median-eminence extract and 1-thyroxine. Then, in order to isolate gonadotrophs, cyanogen bromide-activated Sepharose whichwas conjugated with LHRH (LHRH-Sepharose) was added to the culture medium. Fourteen days after incubation of 2A8 cells with LHRH-Sepharose, agranular and granular cells were rapidly bound to LHRH-Sepharose when fresh serum had previously been added in the medium. The cytoplasm of granular cells that were bound to LHRH-Sepharose contained spherical secretory granules (200-250 nm in diameter). These cells were similar in morphology to the FSH and LH gonadotrophs described by Kurosumi (1968). Moreover, many of them appeared as hypertrophied cells that resembled \"castration\" cells. These results demonstrate that LHRH conjugated to Sepharose can be used to separate gonadotrophs from other 2A8 cells, and it is suggested that the hypertrophy of some cells might be due to persistent stimulation by LHRH which is likely bound to receptors on the cell membrane."}
{"id": "PMID:208776", "title": "The transfer and stable integration of the HSV thymidine kinase gene into mouse cells.", "content": "Treatment of mutant mouse cells (Ltk-) deficient in thymidine kinase with Bam I restriction endonuclease-cleaved HSV-1 DNA results in the appearance of numerous surviving colonies which stably express thte tk+ phenotype. Through a series of electrophoretic fractionations in concert with transfection assays, we isolated a 3.4 kb fragment which contains the thymidine kinase gene and which alone is competent in the biochemical transformation of Ltk- cells. In this report, we have examined the distribution of tk sequences in the DNA of several transformed clones following stable gene transfer. A series of complementary experiments involving reassociation kinetics in solution and annealings with tk DNA to restriction-cleaved cellular DNA following electrophoresis and transfer to filters allow us to make the following general conclusions concerning the fate of the tk gene in all clones examined: the tk gene is present in all cells at a frequency of one copy per chromosomal complement; the tk gene is stably integrated in the DNA of all transformants; and integration is not site-specific and occurs at different loci in the DNA of all transformants examined. The existence of a single active tk gene in tk+ transformants now facilitates an analysis of the sequence organization of tk- mutant cells and provides a useful model system for studies on the transfer of cellular genes.", "contents": "The transfer and stable integration of the HSV thymidine kinase gene into mouse cells. Treatment of mutant mouse cells (Ltk-) deficient in thymidine kinase with Bam I restriction endonuclease-cleaved HSV-1 DNA results in the appearance of numerous surviving colonies which stably express thte tk+ phenotype. Through a series of electrophoretic fractionations in concert with transfection assays, we isolated a 3.4 kb fragment which contains the thymidine kinase gene and which alone is competent in the biochemical transformation of Ltk- cells. In this report, we have examined the distribution of tk sequences in the DNA of several transformed clones following stable gene transfer. A series of complementary experiments involving reassociation kinetics in solution and annealings with tk DNA to restriction-cleaved cellular DNA following electrophoresis and transfer to filters allow us to make the following general conclusions concerning the fate of the tk gene in all clones examined: the tk gene is present in all cells at a frequency of one copy per chromosomal complement; the tk gene is stably integrated in the DNA of all transformants; and integration is not site-specific and occurs at different loci in the DNA of all transformants examined. The existence of a single active tk gene in tk+ transformants now facilitates an analysis of the sequence organization of tk- mutant cells and provides a useful model system for studies on the transfer of cellular genes."}
{"id": "PMID:208777", "title": "Mutants of SV40 with an altered small t protein are reduced in their ability to transform cells.", "content": "Mutants of SV40 with deletions of various sizes mapping between 0.54 and 0.59 on the genome grow at a rate equal to or slightly slower than that of wild-type virus, in a range of host cells. Their ability, however, to induce transformation in several mouse, rat and rabbit cell lines is impaired. The extent of transformation observed is dependent upon the assay used to measure it, but in general, the ability of the mutants to transform falls as the size of the deletion increases. In addition, rat embryo fibroblasts transformed by deletion mutants have fewer of the characteristics of a fully transformed phenotype (for example, growth in low serum, increased saturation density, growth in semi-solid medium) than those transformed by wild-type virus. During lytic infection, immunoprecipitable T antigen produced by the deletion mutants is of the same size as that seen during infection with wild-type virus, and is present at a similar level. Mutant virus-coded small t protein, however, is reduced in size compared with that from wild-type virus. For each mutant, the reduction in protein size is dependent upon the amount of DNA deleted, but not on the relative position of the deletion in the genome. These results demonstrate that the DNA sequences mapping between 0.54 and 0.59 on the viral genome code for the small t protein, and that SV40-induced transformation is at least partially dependent upon the expression of this protein.", "contents": "Mutants of SV40 with an altered small t protein are reduced in their ability to transform cells. Mutants of SV40 with deletions of various sizes mapping between 0.54 and 0.59 on the genome grow at a rate equal to or slightly slower than that of wild-type virus, in a range of host cells. Their ability, however, to induce transformation in several mouse, rat and rabbit cell lines is impaired. The extent of transformation observed is dependent upon the assay used to measure it, but in general, the ability of the mutants to transform falls as the size of the deletion increases. In addition, rat embryo fibroblasts transformed by deletion mutants have fewer of the characteristics of a fully transformed phenotype (for example, growth in low serum, increased saturation density, growth in semi-solid medium) than those transformed by wild-type virus. During lytic infection, immunoprecipitable T antigen produced by the deletion mutants is of the same size as that seen during infection with wild-type virus, and is present at a similar level. Mutant virus-coded small t protein, however, is reduced in size compared with that from wild-type virus. For each mutant, the reduction in protein size is dependent upon the amount of DNA deleted, but not on the relative position of the deletion in the genome. These results demonstrate that the DNA sequences mapping between 0.54 and 0.59 on the viral genome code for the small t protein, and that SV40-induced transformation is at least partially dependent upon the expression of this protein."}
{"id": "PMID:208778", "title": "Complete sequences of the ribosome recognition sites in vesicular stomatitis virus mRNAs: recognition by the 40S and 80S complexes.", "content": "Nucleotide sequences of the ribosome-protected translation initiation sites from the vesicular stomatitis virus (VSV) M and L protein mRNAs have been determined, completing the sequences of the sites from all the VSV mRNAs. A low level of protection at two internal AUG-containing sites in the N mRNA is also described. Small homologies are evident among some of the sites, but there are no obvious features common to all the sites other than a single AUG codon. In contrast, a large homology between the VSV M mRNA site and the alfalfa mosaic virus coat mRNA site (Koper-Zwarthoff et al., 1977) is noted. This homology suggests the existence of a common ancestral gene for these two apparently unrelated viruses. For each VSV mRNA species, the smallest sites protected in either the 40S or 80S initiation complexes are identical. These sites always contained the initiation codon, but only contained the capped 5' end in those mRNAs having the 5' end near the initiation site. If 40S ribosomes bind to the capped 5' end, either they do not protect it from nuclease digestion or the protection is only transitory in some VSV mRNAs. Consideration of the structures of the ribosome binding sites suggests that the differential effects of hypertonic shock on translation (Nuss and Koch, 1976) may be related to the distance between the 5' end of the mRNA and the initiation codon.", "contents": "Complete sequences of the ribosome recognition sites in vesicular stomatitis virus mRNAs: recognition by the 40S and 80S complexes. Nucleotide sequences of the ribosome-protected translation initiation sites from the vesicular stomatitis virus (VSV) M and L protein mRNAs have been determined, completing the sequences of the sites from all the VSV mRNAs. A low level of protection at two internal AUG-containing sites in the N mRNA is also described. Small homologies are evident among some of the sites, but there are no obvious features common to all the sites other than a single AUG codon. In contrast, a large homology between the VSV M mRNA site and the alfalfa mosaic virus coat mRNA site (Koper-Zwarthoff et al., 1977) is noted. This homology suggests the existence of a common ancestral gene for these two apparently unrelated viruses. For each VSV mRNA species, the smallest sites protected in either the 40S or 80S initiation complexes are identical. These sites always contained the initiation codon, but only contained the capped 5' end in those mRNAs having the 5' end near the initiation site. If 40S ribosomes bind to the capped 5' end, either they do not protect it from nuclease digestion or the protection is only transitory in some VSV mRNAs. Consideration of the structures of the ribosome binding sites suggests that the differential effects of hypertonic shock on translation (Nuss and Koch, 1976) may be related to the distance between the 5' end of the mRNA and the initiation codon."}
{"id": "PMID:208779", "title": "Murine interferon system regulation: isolation and characterization of a mutant 3T6 cell engaged in the semiconstitutive synthesis of interferon.", "content": "We describe the isolation and characterization of a virus-resistant mutant of murine 3T6 cells. The mutant, designated 3T6-VrB2, displays a high degree of resistance to infection by members of the toga-, rhabdo- and picornavirus classes. The level of this resistance to infection is similar to the parent 3T6 pretreated with approximately 100 lU/ml of interferon. Upon co-cultivation of 3T6-VrB2 cells with interferon-sensitive mouse cells, an antiviral state is induced in the latter cells as measured by a reduction of virus yield following infection. The nature of the induction is defined by a series of experiments using anti-mouse interferon antiserum. In the presence of this antiserum, the ability of the mutant to induce an antiviral state in interferon-sensitive mouse cells upon co-cultivation is eliminated. Additionally, growth of the mutant cells in the presence of this antiserum causes a reversal of the virus-resistant phenotype. Our results indicate that 3T6-VrB2 contains a mutation affecting the regulation of the murine interferon system such that the cell is engaged in the semiconstitutive synthesis of interferon.", "contents": "Murine interferon system regulation: isolation and characterization of a mutant 3T6 cell engaged in the semiconstitutive synthesis of interferon. We describe the isolation and characterization of a virus-resistant mutant of murine 3T6 cells. The mutant, designated 3T6-VrB2, displays a high degree of resistance to infection by members of the toga-, rhabdo- and picornavirus classes. The level of this resistance to infection is similar to the parent 3T6 pretreated with approximately 100 lU/ml of interferon. Upon co-cultivation of 3T6-VrB2 cells with interferon-sensitive mouse cells, an antiviral state is induced in the latter cells as measured by a reduction of virus yield following infection. The nature of the induction is defined by a series of experiments using anti-mouse interferon antiserum. In the presence of this antiserum, the ability of the mutant to induce an antiviral state in interferon-sensitive mouse cells upon co-cultivation is eliminated. Additionally, growth of the mutant cells in the presence of this antiserum causes a reversal of the virus-resistant phenotype. Our results indicate that 3T6-VrB2 contains a mutation affecting the regulation of the murine interferon system such that the cell is engaged in the semiconstitutive synthesis of interferon."}
{"id": "PMID:208784", "title": "Chemotaxis in Dictyostelium discoideum: effect of concanavalin A on chemoattractant mediated cyclic gmp accumulation anlight scattering decrease.", "content": "In cells of the cellular slime mold Dictyostelium discoideum concanavalin A (Con A), at a concentration of 100 microgram per ml, inhibits folic acid and cyclic AMP induced decrease in light scattering. Con A has no effect on folic acid mediated cyclic GMP accumulation and increases cyclic AMP mediated cyclic GMP accumulation two-fold. At a lower Con A concentration, 10 microgram per ml, changes in light scattering induced by folic acid are normal and cyclic AMP induces a monophasic instead of a biphasic response. The stimulatory effect of Con A on cyclic AMP mediated cyclic GMP accumulation is still observable at 10 microgram Con A per ml. When cells are repeatedly stimulated with cyclic AMP, a decrease in light scattering without being accompanied by changes in cyclic GMP concentration is observed. Based on these results a model for chemotaxis is proposed.", "contents": "Chemotaxis in Dictyostelium discoideum: effect of concanavalin A on chemoattractant mediated cyclic gmp accumulation anlight scattering decrease. In cells of the cellular slime mold Dictyostelium discoideum concanavalin A (Con A), at a concentration of 100 microgram per ml, inhibits folic acid and cyclic AMP induced decrease in light scattering. Con A has no effect on folic acid mediated cyclic GMP accumulation and increases cyclic AMP mediated cyclic GMP accumulation two-fold. At a lower Con A concentration, 10 microgram per ml, changes in light scattering induced by folic acid are normal and cyclic AMP induces a monophasic instead of a biphasic response. The stimulatory effect of Con A on cyclic AMP mediated cyclic GMP accumulation is still observable at 10 microgram Con A per ml. When cells are repeatedly stimulated with cyclic AMP, a decrease in light scattering without being accompanied by changes in cyclic GMP concentration is observed. Based on these results a model for chemotaxis is proposed."}
{"id": "PMID:208789", "title": "[Effect of synthetic ACTH (beta 1-23 corticotropin) on gestation and parturition in rats].", "content": "Daily administration of synthetic ACTH (betaI-23 corticotrophine) from day 15 of pregnancy induces delay or inhibition of parturition in normal or ovariectomized Rats injected or not with estradiol. Parturition takes place at approximatively normal time, when ACTH is stopped and estradiol continued. Radio-immunological assays show an increase of blood progesterone level after ACTH administration in castrated, but not in castrated and adrenalectomized Rats. Mechanisms of ACTH action are discussed.", "contents": "[Effect of synthetic ACTH (beta 1-23 corticotropin) on gestation and parturition in rats]. Daily administration of synthetic ACTH (betaI-23 corticotrophine) from day 15 of pregnancy induces delay or inhibition of parturition in normal or ovariectomized Rats injected or not with estradiol. Parturition takes place at approximatively normal time, when ACTH is stopped and estradiol continued. Radio-immunological assays show an increase of blood progesterone level after ACTH administration in castrated, but not in castrated and adrenalectomized Rats. Mechanisms of ACTH action are discussed."}
{"id": "PMID:208790", "title": "[Aflatoxin is present in primary liver cancers in residents of Za\u00efre].", "content": "Aflatoxin is localized by fluorescence microscopy in primary liver cancer in man from Za\u00efre.", "contents": "[Aflatoxin is present in primary liver cancers in residents of Za\u00efre]. Aflatoxin is localized by fluorescence microscopy in primary liver cancer in man from Za\u00efre."}
{"id": "PMID:208791", "title": "[Studies of spin-labeled spectrin].", "content": "Spectrin isolated from human erythrocytes has been spin-labeled with five maleimide nitroxides. The mobility of the labels is strongly dependent on their size, and on the temperature. A thermal transition of spectrin is shown to occur above 30 degrees C. Calcium and magnesium provoke a strong immobilization of the labels. This effect is yet more pronounced when spectrin is allowed to reassociate with the cytoplasmic surface of the membrane.", "contents": "[Studies of spin-labeled spectrin]. Spectrin isolated from human erythrocytes has been spin-labeled with five maleimide nitroxides. The mobility of the labels is strongly dependent on their size, and on the temperature. A thermal transition of spectrin is shown to occur above 30 degrees C. Calcium and magnesium provoke a strong immobilization of the labels. This effect is yet more pronounced when spectrin is allowed to reassociate with the cytoplasmic surface of the membrane."}
{"id": "PMID:208792", "title": "[Loss of steroidogenesis in a mouse adrenal cell line after simian adenovirus 7 (SA7) transformation].", "content": "After transformation by the simian adenovirus 7 (SA7), the Y-1 Mouse adrenal tumor cells are no longer able to produce stero\u00efds either spontaneously, or after specific stimulation. Nevertheless, these stimulations are able to increase the level of cAMP both in transformed and original cell line. The differentiation is associated with an intracellular modification of stero\u00efdogenesis which seems to be localized in the metabolic chain of stero\u00efd synthesis after the increase of the cAMP level.", "contents": "[Loss of steroidogenesis in a mouse adrenal cell line after simian adenovirus 7 (SA7) transformation]. After transformation by the simian adenovirus 7 (SA7), the Y-1 Mouse adrenal tumor cells are no longer able to produce stero\u00efds either spontaneously, or after specific stimulation. Nevertheless, these stimulations are able to increase the level of cAMP both in transformed and original cell line. The differentiation is associated with an intracellular modification of stero\u00efdogenesis which seems to be localized in the metabolic chain of stero\u00efd synthesis after the increase of the cAMP level."}
{"id": "PMID:208788", "title": "[Relations between malaria and Burkitt's lymphoma].", "content": "Malaria, especially forest malaria, is the environmental factor which creates endemic conditions for the Esptein-Barr virus related Burkitt's lymphoma. The Plasmodium seems active through a mitogenic factor rather than through the so often invoked immunological depresssion.", "contents": "[Relations between malaria and Burkitt's lymphoma]. Malaria, especially forest malaria, is the environmental factor which creates endemic conditions for the Esptein-Barr virus related Burkitt's lymphoma. The Plasmodium seems active through a mitogenic factor rather than through the so often invoked immunological depresssion."}
{"id": "PMID:208793", "title": "[Modulator role of prostaglandins (Pg) in adrenergic neurotransmission in carotid sinus].", "content": "In Rabbit carotid sinus, the presence of sympathetic nerve endings capable of releasing noradrenaline has been demonstrated. The release of NA in response to sympathetic nerve stimulation was decreased by PgE2 and a precursor of Pg (arachidonic acid) but was strongly increased by an inhibitor of Pg biosynthesis (indomethacin). The experiments carried out demonstrated that freshly synthesized Pg acts in the same way as exogenous Pg and suggested that Pg could have a regulating effect on adrenergic neurotransmission in carotid sinus. The role of this regulating mechanism in the physiology of carotid sinus has been discussed.", "contents": "[Modulator role of prostaglandins (Pg) in adrenergic neurotransmission in carotid sinus]. In Rabbit carotid sinus, the presence of sympathetic nerve endings capable of releasing noradrenaline has been demonstrated. The release of NA in response to sympathetic nerve stimulation was decreased by PgE2 and a precursor of Pg (arachidonic acid) but was strongly increased by an inhibitor of Pg biosynthesis (indomethacin). The experiments carried out demonstrated that freshly synthesized Pg acts in the same way as exogenous Pg and suggested that Pg could have a regulating effect on adrenergic neurotransmission in carotid sinus. The role of this regulating mechanism in the physiology of carotid sinus has been discussed."}
{"id": "PMID:208794", "title": "[Inhibitory effects of LHRH on ovarian LH receptors in rats].", "content": "The administration of LHRH or of its analog [D-Ala6, des-Gly-NH10(2)] LHRH ethylamide to the female rat on day 10 of gestation resulted in termination of pregnancy and in a marked decrease in ovarian LH receptors and plasma progesterone level. Asingle injection of either compound during diestrus I also led to a decrease in LH receptors. These data demonstrate the high sensitivity of the control of ovarian LH receptors by circulating gonadotrophins and suggest that the contraceptive action of pre- and postcoitally administered LHRH is mediated by negative control of LH receptors.", "contents": "[Inhibitory effects of LHRH on ovarian LH receptors in rats]. The administration of LHRH or of its analog [D-Ala6, des-Gly-NH10(2)] LHRH ethylamide to the female rat on day 10 of gestation resulted in termination of pregnancy and in a marked decrease in ovarian LH receptors and plasma progesterone level. Asingle injection of either compound during diestrus I also led to a decrease in LH receptors. These data demonstrate the high sensitivity of the control of ovarian LH receptors by circulating gonadotrophins and suggest that the contraceptive action of pre- and postcoitally administered LHRH is mediated by negative control of LH receptors."}
{"id": "PMID:208795", "title": "[Role of alpha and beta adrenoceptors in the regulation of adrenergic neurotransmission in the carotid sinus].", "content": "The experiments carried out showed the presence- in sympathetic nerve endings ot the carotid sinus- of alpha and beta adrenoceptors which by means of respective negative and positive feedback processes, modulated NA release induced by a sympathetic nerve stimulation. Similarly, Pgs acted by means of a negative feedback mechanism to regulated adrenergic neuro-transmission in carotid sinus but they could not be considered as the chemical mediators of either alpha or beta adrenoceptors.", "contents": "[Role of alpha and beta adrenoceptors in the regulation of adrenergic neurotransmission in the carotid sinus]. The experiments carried out showed the presence- in sympathetic nerve endings ot the carotid sinus- of alpha and beta adrenoceptors which by means of respective negative and positive feedback processes, modulated NA release induced by a sympathetic nerve stimulation. Similarly, Pgs acted by means of a negative feedback mechanism to regulated adrenergic neuro-transmission in carotid sinus but they could not be considered as the chemical mediators of either alpha or beta adrenoceptors."}
{"id": "PMID:208796", "title": "[Effect of dibutyryl cyclic AMP on cerebral energy charge and electrocorticographic activity in rats under asphyxic hypoxia].", "content": "In Rats anesthetized with pentobarbital and submitted to brief asphyxic episodes, intracerebroventricular administration of dibutyryl cyclic AMP inhibits the decrease of energy charge, delays the disappearance of electrocorticographic activity (E Co G) and shortens the recovery time of E Co G.", "contents": "[Effect of dibutyryl cyclic AMP on cerebral energy charge and electrocorticographic activity in rats under asphyxic hypoxia]. In Rats anesthetized with pentobarbital and submitted to brief asphyxic episodes, intracerebroventricular administration of dibutyryl cyclic AMP inhibits the decrease of energy charge, delays the disappearance of electrocorticographic activity (E Co G) and shortens the recovery time of E Co G."}
{"id": "PMID:208797", "title": "[Murine type C endogenous virus expression in murine 129 teratocarcinoma cell line].", "content": "Murine type C viral information is detectable in the cellular genome of both differentiated and undifferentiated cell lines derived from 129 Mouse teratocarcinoma. Cytoplasmic RNA expression which is negligible in differentiated cells, is significantly higher in multipotential undifferentiated cells. Furthermore it was observed that in vitro differentiation of multipotent cells leads to a decrease of this expression.", "contents": "[Murine type C endogenous virus expression in murine 129 teratocarcinoma cell line]. Murine type C viral information is detectable in the cellular genome of both differentiated and undifferentiated cell lines derived from 129 Mouse teratocarcinoma. Cytoplasmic RNA expression which is negligible in differentiated cells, is significantly higher in multipotential undifferentiated cells. Furthermore it was observed that in vitro differentiation of multipotent cells leads to a decrease of this expression."}
{"id": "PMID:208798", "title": "[Inhibitory effects of LHRH on LH receptors in the rat testis].", "content": "A single injection of LHRH to the adult male rat, as of its analog [D-Ala6, des-Gly-NH102] LHRH ethylamide, resulted in a marked decrease in LH receptors in the tests. Plasma testosterone level and the weight of the seminal vesicles and prostate were also decreased after treatment. These data demonstrate that LHRH can decrease the sensitivity of LH receptors and testicular function in the rat.", "contents": "[Inhibitory effects of LHRH on LH receptors in the rat testis]. A single injection of LHRH to the adult male rat, as of its analog [D-Ala6, des-Gly-NH102] LHRH ethylamide, resulted in a marked decrease in LH receptors in the tests. Plasma testosterone level and the weight of the seminal vesicles and prostate were also decreased after treatment. These data demonstrate that LHRH can decrease the sensitivity of LH receptors and testicular function in the rat."}
{"id": "PMID:208799", "title": "[Absence of lipolytic action of adrenaline on a human subcutaneous adipose tissue. Role of alpha-adrenergic receptors].", "content": "Epinephrine cannot stimulate adipocytes' lipolysis of human subcutaneous adipose tissue (lateral part of the thigh) while a clear lipolytic action can be shown on the omental tissue. However, at the same concentrations, isoproterenol (a beta-agonist) exerts a strong adipokinetic effect on adipocytes of the both types of adipose tissue. An alpha-adrenolytic (phentolamine) enhances the lipolytic action of epinephrine on the omental adipose tissue and unmasks a lipolytic action of epinephrine on the subcutaneous. Epinephrine antagonizes the lipolysis induced by theophyline on the subscutaneous adipocytes, this action is increased by propranolol (a beta-adrenergic blocking agent). The unresponsiveness to epinephrine of the subcutaneous adipose tissue studied here could be linked to a strong antilipolytic alpha-adrenergic effect.", "contents": "[Absence of lipolytic action of adrenaline on a human subcutaneous adipose tissue. Role of alpha-adrenergic receptors]. Epinephrine cannot stimulate adipocytes' lipolysis of human subcutaneous adipose tissue (lateral part of the thigh) while a clear lipolytic action can be shown on the omental tissue. However, at the same concentrations, isoproterenol (a beta-agonist) exerts a strong adipokinetic effect on adipocytes of the both types of adipose tissue. An alpha-adrenolytic (phentolamine) enhances the lipolytic action of epinephrine on the omental adipose tissue and unmasks a lipolytic action of epinephrine on the subcutaneous. Epinephrine antagonizes the lipolysis induced by theophyline on the subscutaneous adipocytes, this action is increased by propranolol (a beta-adrenergic blocking agent). The unresponsiveness to epinephrine of the subcutaneous adipose tissue studied here could be linked to a strong antilipolytic alpha-adrenergic effect."}
{"id": "PMID:208800", "title": "[Analytical morphodynamics. Practical applications].", "content": "The analytical morphodynamic method, based on the study of the fate of the biogic units of an organ at the level of well or poorly developed lesions, has been applied to the analysis of chronic obliterating arteriopathies of the extremities, of benign tumors of the mammary parenchyma, and of malignant hepatomas. In morbid states as different as a reactive process and a benign or malignant neoplastic process, it allowed to reconstritute the histogenesis of complex tissue changes and led to interesting prospects, in the field of general biology and pathogenesis.", "contents": "[Analytical morphodynamics. Practical applications]. The analytical morphodynamic method, based on the study of the fate of the biogic units of an organ at the level of well or poorly developed lesions, has been applied to the analysis of chronic obliterating arteriopathies of the extremities, of benign tumors of the mammary parenchyma, and of malignant hepatomas. In morbid states as different as a reactive process and a benign or malignant neoplastic process, it allowed to reconstritute the histogenesis of complex tissue changes and led to interesting prospects, in the field of general biology and pathogenesis."}
{"id": "PMID:208802", "title": "The interaction of human plasma glycosaminoglycans with plasma lipoproteins. II. Hemagglutination studies.", "content": "Formalinized, tannic acid-treated sheep erythrocytes coated with low density lipoproteins (LSL) or apoprotein B (apo-B) are are agglutinated by anti-apo-B immunserum. Those coated with high density lipoproteins (HDL) or apoprotein A-I(apo-A-I) are agglutinated by anti-apo-A-I immunserum. These coated formocells have been used to study the interactions of lipoproteins and apoproteins with plasma glycosaminoglycans (GAG). The sulfate-rich species of plasma GAG agglutinates cells coated with LDL, HDL, apo-B, and apo-A-I at ionic concentrations above 0.15 M. The less-sulfated species of plasma GAG does not agglutinate the coated cells but inhibits the agglutination caused by the sulfate-rich species. Treatment of the sulfate-rich GAG with papain causes a reduction in molecular weight by one-half and also causes a loss of its agglutinating activity. These results suggest that the sulfate-rich plasma GAG, consisting of two glycan chains linked to a peptide backbone, cause agglutination by binding to two or more formocells. In contrast, the less-sulfated plasma GAG, consisting of single, short glycan chains, are incapable of causing agglutination but may prevent it by covering specific binding sites present on the coated cells.", "contents": "The interaction of human plasma glycosaminoglycans with plasma lipoproteins. II. Hemagglutination studies. Formalinized, tannic acid-treated sheep erythrocytes coated with low density lipoproteins (LSL) or apoprotein B (apo-B) are are agglutinated by anti-apo-B immunserum. Those coated with high density lipoproteins (HDL) or apoprotein A-I(apo-A-I) are agglutinated by anti-apo-A-I immunserum. These coated formocells have been used to study the interactions of lipoproteins and apoproteins with plasma glycosaminoglycans (GAG). The sulfate-rich species of plasma GAG agglutinates cells coated with LDL, HDL, apo-B, and apo-A-I at ionic concentrations above 0.15 M. The less-sulfated species of plasma GAG does not agglutinate the coated cells but inhibits the agglutination caused by the sulfate-rich species. Treatment of the sulfate-rich GAG with papain causes a reduction in molecular weight by one-half and also causes a loss of its agglutinating activity. These results suggest that the sulfate-rich plasma GAG, consisting of two glycan chains linked to a peptide backbone, cause agglutination by binding to two or more formocells. In contrast, the less-sulfated plasma GAG, consisting of single, short glycan chains, are incapable of causing agglutination but may prevent it by covering specific binding sites present on the coated cells."}
{"id": "PMID:208803", "title": "The estimation of pyrophosphate in urine with uridine-5'-diphosphoglucose pyrophosphorylase.", "content": "The concentration of pyrophosphate in urine has been determined using the enzyme uridine-5'-diphosphoglucose pyrophosphorylase. The technique is relatively quick and easy to perform. Reproducibility of results was good, and results from recovery experiments were excellent. The mean concentration of pyrophosphate found in early morning urine samples from 14 normal adults was identical with that reported by other workers using an ion-exchange method to measure pyrophosphate. The pyrophosphate concentration was related approximately to the phosphate concentration.", "contents": "The estimation of pyrophosphate in urine with uridine-5'-diphosphoglucose pyrophosphorylase. The concentration of pyrophosphate in urine has been determined using the enzyme uridine-5'-diphosphoglucose pyrophosphorylase. The technique is relatively quick and easy to perform. Reproducibility of results was good, and results from recovery experiments were excellent. The mean concentration of pyrophosphate found in early morning urine samples from 14 normal adults was identical with that reported by other workers using an ion-exchange method to measure pyrophosphate. The pyrophosphate concentration was related approximately to the phosphate concentration."}
{"id": "PMID:208804", "title": "Apolipoprotein A-1 in cholestatic liver diseases.", "content": "The apolipoprotein A-1 in cholestatic liver diseases was determined by rocket immunoelectrophoresis. A decrease in the serum apo A-1 was generally observed in LP-X positive liver disease, particularly in the patients with extrahepatic biliary obstruction. With reference to LP-X levels and LCAT activity, the results indicated that not only hepatocellular damage but also cholestasis contribute to the decrease of apo A-1 concentration in patients with liver disease.", "contents": "Apolipoprotein A-1 in cholestatic liver diseases. The apolipoprotein A-1 in cholestatic liver diseases was determined by rocket immunoelectrophoresis. A decrease in the serum apo A-1 was generally observed in LP-X positive liver disease, particularly in the patients with extrahepatic biliary obstruction. With reference to LP-X levels and LCAT activity, the results indicated that not only hepatocellular damage but also cholestasis contribute to the decrease of apo A-1 concentration in patients with liver disease."}
{"id": "PMID:208806", "title": "Pathology of salivary glandular tumours.", "content": "The incidence and pathological features of the various tumours arising from salivary glandular tissues are described in the light of the World Health Organization classification of these tumours. The modern concepts relating to their histogenesis are outlined and some of the difficulties which may be encountered in their histological diagnosis are also discussed.", "contents": "Pathology of salivary glandular tumours. The incidence and pathological features of the various tumours arising from salivary glandular tissues are described in the light of the World Health Organization classification of these tumours. The modern concepts relating to their histogenesis are outlined and some of the difficulties which may be encountered in their histological diagnosis are also discussed."}
{"id": "PMID:208807", "title": "Heterogeneity of the clinical syndrome in patients with systemic lupus erythematosus and genetic deficiency of the second complement component.", "content": "Two patients with systemic lupus erythematosus associated with homozygous deficiency of the second complement component (SLE-C2D) illustrate the different clinical disease patterns found in patients with this illness. Despite the differences in extent and severity of clinical manifestations and serological findings, the renal disease was similar and kidney function was well preserved in both patients. Renal microscopic changes were focal and segmental, deposits of immuno-globulins and complement components were present by immunofluorescent staining, and dense deposits were seen by electron microscopy. Tubulo-reticular inclusion bodies were found in glomerular endothelial cells and lymphocytes of both patients, but not in the lymphocytes of a clinically healthy C2D sibling. The findings in these two patients stress the importance of careful evaluation to determine the presence of systemic disease in patients with SLE-C2D and suggest that an intact classic complement pathway is important in the development of severe lupus, nephritis, but is not needed in the pathogenesis of lupus skin lesions.", "contents": "Heterogeneity of the clinical syndrome in patients with systemic lupus erythematosus and genetic deficiency of the second complement component. Two patients with systemic lupus erythematosus associated with homozygous deficiency of the second complement component (SLE-C2D) illustrate the different clinical disease patterns found in patients with this illness. Despite the differences in extent and severity of clinical manifestations and serological findings, the renal disease was similar and kidney function was well preserved in both patients. Renal microscopic changes were focal and segmental, deposits of immuno-globulins and complement components were present by immunofluorescent staining, and dense deposits were seen by electron microscopy. Tubulo-reticular inclusion bodies were found in glomerular endothelial cells and lymphocytes of both patients, but not in the lymphocytes of a clinically healthy C2D sibling. The findings in these two patients stress the importance of careful evaluation to determine the presence of systemic disease in patients with SLE-C2D and suggest that an intact classic complement pathway is important in the development of severe lupus, nephritis, but is not needed in the pathogenesis of lupus skin lesions."}
{"id": "PMID:208810", "title": "Viral infections in pregnancy.", "content": "The responsibility of the physician for viral infections in pregnancy has changed dramatically in the last 15 years. Genital herpes infections have become much more frequent, and the recognition of these infections in women near term is particularly important. Cytomegaloviruses have been found to be the most commom cause of congenital infection, but no satisfactory methods are available for prevention or treatment. Varicella is now recognized as a teratogen when infection occurs in the first 4 months of pregnancy. It can also cause severe generalized disease in the newborn when infection takes place in the last few days of gestation. Hepatitis B infections are becoming more frequent in many populations, and this virus can transmit to the child, particularly when maternal infection occurs in the last trimester. Venezuelan equine encephalitis virus has been found to be a teratogen. This must be considered in southern states such as Florida and Texas, as well as in Central and South America. Rubella, fortunately appears to be coming under control with the intensive use of serodiagnosis and vaccines in the United States.", "contents": "Viral infections in pregnancy. The responsibility of the physician for viral infections in pregnancy has changed dramatically in the last 15 years. Genital herpes infections have become much more frequent, and the recognition of these infections in women near term is particularly important. Cytomegaloviruses have been found to be the most commom cause of congenital infection, but no satisfactory methods are available for prevention or treatment. Varicella is now recognized as a teratogen when infection occurs in the first 4 months of pregnancy. It can also cause severe generalized disease in the newborn when infection takes place in the last few days of gestation. Hepatitis B infections are becoming more frequent in many populations, and this virus can transmit to the child, particularly when maternal infection occurs in the last trimester. Venezuelan equine encephalitis virus has been found to be a teratogen. This must be considered in southern states such as Florida and Texas, as well as in Central and South America. Rubella, fortunately appears to be coming under control with the intensive use of serodiagnosis and vaccines in the United States."}
{"id": "PMID:208813", "title": "An outbreak of the conjunctival form of infectious bovine rhinotracheitis.", "content": "An outbreak of severe conjunctivitis involved approximately 30% of a dairy herd of 118 cattle. Infectious Bovine Rhinotracheitis (IBR) virus was identified by cytopathic effects and fluorescent antibody techniques from conjunctival swabs of affected animals. The disease typically presented as a unilateral ocular disease with systemic signs of pyrexia, inappetance, decreased milk production, and some subsequent abortions.", "contents": "An outbreak of the conjunctival form of infectious bovine rhinotracheitis. An outbreak of severe conjunctivitis involved approximately 30% of a dairy herd of 118 cattle. Infectious Bovine Rhinotracheitis (IBR) virus was identified by cytopathic effects and fluorescent antibody techniques from conjunctival swabs of affected animals. The disease typically presented as a unilateral ocular disease with systemic signs of pyrexia, inappetance, decreased milk production, and some subsequent abortions."}
{"id": "PMID:208814", "title": "Estimating adrenal cortical function in dogs with ACTH.", "content": "The peripheral blood response to intramuscular injection of 10 units ACTH in dogs was investigated because no experimental evidence for the standardization of this procedure for clinical use was available. Following the injection of ACTH in sodium chloride solution, neutrophilia, monocytosis, eosinopenia, and lymphopenia occurred. With the exception of eosinopenia, the greatest change in the concentration of each cell type in peripheral blood occurred between 2 and 4 hours post injection. The maximum change in eosinophil numbers occurred between 4 and 6 hours post injection. When all cell types were considered, 4 hours post injection was the most suitable time to measure the cellular response in peripheral blood in dogs which respond to ACTH. The data indicate that change in the ratio of neutrophils to lymphocytes (N/L) prior to and at 2 to 4 hours after ACTH injection in normal dogs was a sensitive index of response and occured sooner than eosinopenia. The extent of change in the N/L ratio was such that accuracy in interpretation could be obtained by counting as few as 40 cells.", "contents": "Estimating adrenal cortical function in dogs with ACTH. The peripheral blood response to intramuscular injection of 10 units ACTH in dogs was investigated because no experimental evidence for the standardization of this procedure for clinical use was available. Following the injection of ACTH in sodium chloride solution, neutrophilia, monocytosis, eosinopenia, and lymphopenia occurred. With the exception of eosinopenia, the greatest change in the concentration of each cell type in peripheral blood occurred between 2 and 4 hours post injection. The maximum change in eosinophil numbers occurred between 4 and 6 hours post injection. When all cell types were considered, 4 hours post injection was the most suitable time to measure the cellular response in peripheral blood in dogs which respond to ACTH. The data indicate that change in the ratio of neutrophils to lymphocytes (N/L) prior to and at 2 to 4 hours after ACTH injection in normal dogs was a sensitive index of response and occured sooner than eosinopenia. The extent of change in the N/L ratio was such that accuracy in interpretation could be obtained by counting as few as 40 cells."}
{"id": "PMID:208820", "title": "Cytologic examination and viral and bacterial culture in herpes simplex, herpes zoster, and varicella.", "content": "Cytologic examination of epithelial cells from the base of vesicles, virus isolation, and bacterial culture were carried out in thirty-one patients with herpes simplex, in eleven patients with herpes zoster, and in three patients with varicella. Determination of herpes simplex complement fixation reaction was made in the patients with herpes simplex. Cytologic manifestations consistent with herpes were found 65 percent of patients with herpes simplex, while herpesvirus hominis was isolated in 77 percent of these patients. Diagnostic cytologic manifestations were found in 82 percent of the patients with herpes zoster or varicella. Varicella-zoster virus was isolated in 27 percent of these patients. The presence of pathogenic bacteria did not seem to influence the frequency of virus isolation or finding of characteristic cytologic features.", "contents": "Cytologic examination and viral and bacterial culture in herpes simplex, herpes zoster, and varicella. Cytologic examination of epithelial cells from the base of vesicles, virus isolation, and bacterial culture were carried out in thirty-one patients with herpes simplex, in eleven patients with herpes zoster, and in three patients with varicella. Determination of herpes simplex complement fixation reaction was made in the patients with herpes simplex. Cytologic manifestations consistent with herpes were found 65 percent of patients with herpes simplex, while herpesvirus hominis was isolated in 77 percent of these patients. Diagnostic cytologic manifestations were found in 82 percent of the patients with herpes zoster or varicella. Varicella-zoster virus was isolated in 27 percent of these patients. The presence of pathogenic bacteria did not seem to influence the frequency of virus isolation or finding of characteristic cytologic features."}
{"id": "PMID:208822", "title": "Behaviour of the mitochondrial respiratory chain in vivo.", "content": "The interrelation of neuronal function and oxidative metabolism of the brain is most incisively studied by optical techniques in vivo. When O2 becomes limited the respiratory chain becomes reduced, extracellular potassium activity is increased, the EEG is depressed and excitability declines, all as expected. Under mildly hyperoxic conditions however, the opposite responses occur, which indicate an absence of a critical tissue Po2 and a continuum of dependence on the O2 concentration, including levels well above the limits for maximal activity of the respiratory chain in isolated mitochondria in vivo. The unexpectedly high steady state of reduction of cytochrome a, a3 provides the basis for a new hypothesis of an extra energy conservation site between cytochrome a3 and O2 and leads to a consideration of a reaction mechanism of O2 with four electrons and four H+ ions occurring at an enzymically active centre of cytochrome a, a3. A special function of the cytochrome a, a3 complex is implied in regulating cellular K+ transport and thus excitability.", "contents": "Behaviour of the mitochondrial respiratory chain in vivo. The interrelation of neuronal function and oxidative metabolism of the brain is most incisively studied by optical techniques in vivo. When O2 becomes limited the respiratory chain becomes reduced, extracellular potassium activity is increased, the EEG is depressed and excitability declines, all as expected. Under mildly hyperoxic conditions however, the opposite responses occur, which indicate an absence of a critical tissue Po2 and a continuum of dependence on the O2 concentration, including levels well above the limits for maximal activity of the respiratory chain in isolated mitochondria in vivo. The unexpectedly high steady state of reduction of cytochrome a, a3 provides the basis for a new hypothesis of an extra energy conservation site between cytochrome a3 and O2 and leads to a consideration of a reaction mechanism of O2 with four electrons and four H+ ions occurring at an enzymically active centre of cytochrome a, a3. A special function of the cytochrome a, a3 complex is implied in regulating cellular K+ transport and thus excitability."}
{"id": "PMID:208823", "title": "Ambulatory detoxification of heroin addicts: a follow-up study.", "content": "The present study was devised to investigate whether or not 18 psychosocial characteristics of 141 male and 43 female heroin addicts who entered a 21-day ambulatory detoxification program were correlated with (1) length of stay, (2) completing the full course of detoxification, (3) being successfully transferred to aftercare treatment, and (4) being locatable for follow-up one month later. The study also described the status of the patients who were locatable one month after receiving their last dose of methadone in the detoxification program. Only 74 persons were contacted one month after receiving their last dose of methadone, and they were all in treatment. Eighty-three addicts were transferred to other programs before leaving the detoxification program. There were only two significant relationships between the 18 psychosocial characteristics and the four dependent variables. Number of arrests was inversely related to length of stay, and whites were more likely to be transferred to an aftercare program than blacks. The implications of the results for evaluating other ambulatory detoxification programs and for improving retention rates were discussed.", "contents": "Ambulatory detoxification of heroin addicts: a follow-up study. The present study was devised to investigate whether or not 18 psychosocial characteristics of 141 male and 43 female heroin addicts who entered a 21-day ambulatory detoxification program were correlated with (1) length of stay, (2) completing the full course of detoxification, (3) being successfully transferred to aftercare treatment, and (4) being locatable for follow-up one month later. The study also described the status of the patients who were locatable one month after receiving their last dose of methadone in the detoxification program. Only 74 persons were contacted one month after receiving their last dose of methadone, and they were all in treatment. Eighty-three addicts were transferred to other programs before leaving the detoxification program. There were only two significant relationships between the 18 psychosocial characteristics and the four dependent variables. Number of arrests was inversely related to length of stay, and whites were more likely to be transferred to an aftercare program than blacks. The implications of the results for evaluating other ambulatory detoxification programs and for improving retention rates were discussed."}
{"id": "PMID:208825", "title": "[Comparative therapeutic investigations of pivmecillinam and amoxycillin (author's transl)].", "content": "The therapeutic value of pivmecillinam and amoxycillin in urinary tract infections was compared in a double blind study. No therapeutic superiority or inferiority of either substance could be demonstrated. The study shows that a therapeutic comparison of two antibiotics using everyday treatment is possible. Before the introduction of new antibiotics at least equal effectiveness of the substance should be documented with appropriate investigations.", "contents": "[Comparative therapeutic investigations of pivmecillinam and amoxycillin (author's transl)]. The therapeutic value of pivmecillinam and amoxycillin in urinary tract infections was compared in a double blind study. No therapeutic superiority or inferiority of either substance could be demonstrated. The study shows that a therapeutic comparison of two antibiotics using everyday treatment is possible. Before the introduction of new antibiotics at least equal effectiveness of the substance should be documented with appropriate investigations."}
{"id": "PMID:208830", "title": "Adrenal contribution to circulating estrogens in woman.", "content": "To study the contribution of adrenal glands to circulating estrogens in woman, the concentrations of estrone (E1), estradiol-17 beta (E2), and estriol (E3) in adrenal and peripheral venous blood were measured by radioimmunoassay and the grandular secretion of estrogens after ACTH stimulation was investigated by analyzing the adrenal vein levels of these steroids in patients with breast cancer who were undergoing a therapeutic adrenal operation. Furthermore, adrenal secretion rates of estrogens and cortisol were estimated. It was shown that there existed greater concentrations of estrogens in adrenal vein than in peripheral blood; about 3 times higher for E1 (p less than 0.001), and 2 times higher for E2 and E3 (p less than 0.05). Administration of ACTH caused a significant increase of E1 and E2 concentrations in adrenal venous blood to mean 150% of the basal levels that was comparable to the increase of cortisol. Apparent adrenal secretion rates of estrogens estimated under surgical situation were calculated to be 7.7 +/- 1.7 (M +/- SE) microgram/day for E1, 1.9 +/- 0.3 microgram/day for E2, and 0.3 +/- 0.2 microgram/day for E3, while the secretion rate of cortisol was 52.7 +/- 8.2 microgram/min. The present study demonstrates that the direct adrenal secretion of not only E1, but E2 and E3 contributes to the circulating estrogen levels, and it is suggested that the adrenal glands might be responsible for the relatively important source of estrogen production in the aged woman.", "contents": "Adrenal contribution to circulating estrogens in woman. To study the contribution of adrenal glands to circulating estrogens in woman, the concentrations of estrone (E1), estradiol-17 beta (E2), and estriol (E3) in adrenal and peripheral venous blood were measured by radioimmunoassay and the grandular secretion of estrogens after ACTH stimulation was investigated by analyzing the adrenal vein levels of these steroids in patients with breast cancer who were undergoing a therapeutic adrenal operation. Furthermore, adrenal secretion rates of estrogens and cortisol were estimated. It was shown that there existed greater concentrations of estrogens in adrenal vein than in peripheral blood; about 3 times higher for E1 (p less than 0.001), and 2 times higher for E2 and E3 (p less than 0.05). Administration of ACTH caused a significant increase of E1 and E2 concentrations in adrenal venous blood to mean 150% of the basal levels that was comparable to the increase of cortisol. Apparent adrenal secretion rates of estrogens estimated under surgical situation were calculated to be 7.7 +/- 1.7 (M +/- SE) microgram/day for E1, 1.9 +/- 0.3 microgram/day for E2, and 0.3 +/- 0.2 microgram/day for E3, while the secretion rate of cortisol was 52.7 +/- 8.2 microgram/min. The present study demonstrates that the direct adrenal secretion of not only E1, but E2 and E3 contributes to the circulating estrogen levels, and it is suggested that the adrenal glands might be responsible for the relatively important source of estrogen production in the aged woman."}
{"id": "PMID:208831", "title": "Induction of mammary prolactin receptors and lactose synthesis after ovariectomy in the pregnant mouse.", "content": "The development of prolactin receptors in the mammary gland after ovariectomy was investigated in pregnant KA mice. Mice were ovariectomized on day 13 of pregnancy and used for the determination of the amount of specific binding of 125I-labelled prolactin to the mammary tissue, and the contents of lactose and nucleic acids in the mammary gland 0, 8, 24, and 72 hr after the operation. The specific binding of 125I-labelled prolactin, lactose and RNA contents in the mammary gland remained low until 8 hr, sharply increased 24 hr and decreased 72 hr after ovariectomy. When ovariectomized mice were treated with 0.2 mg progesterone, pregnancy was maintained and an increase (1.5-fold) in the amount of specific binding was observed with an increase of lactose content. Five mg progesterone completely inhibited lactose synthesis. Cortisol administered with progesterone did not show any specific change at the dose used (0.5 to 10 mg). Although the amount of specific binding was also increased after hysterectomy, this increase (2-fold) did not fully cover the increase after ovariectomy (3-fold). These results suggest that the recepter site for prolactin is induced before the initiation of lactose synthesis caused by ovariectomy during pregnancy.", "contents": "Induction of mammary prolactin receptors and lactose synthesis after ovariectomy in the pregnant mouse. The development of prolactin receptors in the mammary gland after ovariectomy was investigated in pregnant KA mice. Mice were ovariectomized on day 13 of pregnancy and used for the determination of the amount of specific binding of 125I-labelled prolactin to the mammary tissue, and the contents of lactose and nucleic acids in the mammary gland 0, 8, 24, and 72 hr after the operation. The specific binding of 125I-labelled prolactin, lactose and RNA contents in the mammary gland remained low until 8 hr, sharply increased 24 hr and decreased 72 hr after ovariectomy. When ovariectomized mice were treated with 0.2 mg progesterone, pregnancy was maintained and an increase (1.5-fold) in the amount of specific binding was observed with an increase of lactose content. Five mg progesterone completely inhibited lactose synthesis. Cortisol administered with progesterone did not show any specific change at the dose used (0.5 to 10 mg). Although the amount of specific binding was also increased after hysterectomy, this increase (2-fold) did not fully cover the increase after ovariectomy (3-fold). These results suggest that the recepter site for prolactin is induced before the initiation of lactose synthesis caused by ovariectomy during pregnancy."}
{"id": "PMID:208832", "title": "[The ACTH content of plasma in fetal and newborn swine].", "content": "ACTH concentration has been estimated radioimmunologically in fetal plasma (100th day of gestation) and in plasma of newborn piglets during the first 24 hours of life and in sows. In comparison to the values of ACTH in sows at the 100th day of gestation during anaesthesia (175 pg/ml) and sows at parturition (235 +/- 77 pg/ml) the concentration in fetal (558 +/- 163 pg/ml) and newborn piglets (448 +/- 158 pg/ml) was much higher. On an average ACTH concentration increased during the first 24 hours of life up to 998 +/- 628 pg/ml. The results are compared to those in other species.", "contents": "[The ACTH content of plasma in fetal and newborn swine]. ACTH concentration has been estimated radioimmunologically in fetal plasma (100th day of gestation) and in plasma of newborn piglets during the first 24 hours of life and in sows. In comparison to the values of ACTH in sows at the 100th day of gestation during anaesthesia (175 pg/ml) and sows at parturition (235 +/- 77 pg/ml) the concentration in fetal (558 +/- 163 pg/ml) and newborn piglets (448 +/- 158 pg/ml) was much higher. On an average ACTH concentration increased during the first 24 hours of life up to 998 +/- 628 pg/ml. The results are compared to those in other species."}
{"id": "PMID:208833", "title": "Effect of gonadotropic hormones on the concentration of adenosine 3', 5'-monophosphate in the rat pineal organ.", "content": "Concentration of adenosine 3',5'-monophosphate (cAMP) was investigated in the male rat pineal organ after a treatment with human chorionic gonadotropin (HCG). HCG significantly decreased cAMP concentration in the pineal organ.", "contents": "Effect of gonadotropic hormones on the concentration of adenosine 3', 5'-monophosphate in the rat pineal organ. Concentration of adenosine 3',5'-monophosphate (cAMP) was investigated in the male rat pineal organ after a treatment with human chorionic gonadotropin (HCG). HCG significantly decreased cAMP concentration in the pineal organ."}
{"id": "PMID:208838", "title": "Interchangeable copper and iron proteins in algal photosynthesis. Studies on plastocyanin and cytochrome c-552 in Chlamydomonas.", "content": "The interrelation of the copper protein plastocyanin, and a soluble c-type cytochrome, c-552, in photosynthetic electron transport has been studied in the genus Chlamydomonas. With C. reinhardtii the plastocyanin: cytochrome c-552 ratio could be changed from 300:1 less than 1:16 simply by omitting copper from the medium, without any other detectable change. Plastocyanin was indetectable in a second species, C. mundana, for which the cytochrome c-552 level was always very high. The properties of Levine's C. reinhardtii mutant lacking plastocyanin, ac-208, were studies and it was found that the photosynthetic capabilities of a suppressed phenotype and suppressed genotype could be explained by reference to the cytochrome c-552 levels. Both proteins were successfully used in reconstitution experiments with chloroplast fragments. Both showed very fast kinetics for reduction by purified Chlamydomonas cytochrome f, but the rate of electron transfer from one to the other was much slower. It is concluded that they constitute an interchangeable pair, and the rationale for this and possible analogies are both discussed.", "contents": "Interchangeable copper and iron proteins in algal photosynthesis. Studies on plastocyanin and cytochrome c-552 in Chlamydomonas. The interrelation of the copper protein plastocyanin, and a soluble c-type cytochrome, c-552, in photosynthetic electron transport has been studied in the genus Chlamydomonas. With C. reinhardtii the plastocyanin: cytochrome c-552 ratio could be changed from 300:1 less than 1:16 simply by omitting copper from the medium, without any other detectable change. Plastocyanin was indetectable in a second species, C. mundana, for which the cytochrome c-552 level was always very high. The properties of Levine's C. reinhardtii mutant lacking plastocyanin, ac-208, were studies and it was found that the photosynthetic capabilities of a suppressed phenotype and suppressed genotype could be explained by reference to the cytochrome c-552 levels. Both proteins were successfully used in reconstitution experiments with chloroplast fragments. Both showed very fast kinetics for reduction by purified Chlamydomonas cytochrome f, but the rate of electron transfer from one to the other was much slower. It is concluded that they constitute an interchangeable pair, and the rationale for this and possible analogies are both discussed."}
{"id": "PMID:208840", "title": "Adenosine 3':5'-monophosphate in perinatal rat liver. Ontogeny and response to hormones.", "content": "Developmental changes in the concentration of adenosine 3':5'-monophosphate (cyclic AMP) and the effects of glucagon and epinephrine were studied in the perinatal rat liver. Hepatic cyclic AMP concentration doubled during the last day of gestation. After birth, the cyclic AMP concentration continued to increase and maximal levels were observed on the fifth postnatal day. Surgical delivery of foetuses on days 20, 21 and 22 of gestation resulted in a rapid increase in cyclic AMP concentration. Maximal concentrations were reached within one hour of delivery in the day-21 and day-22 foetuses. However with surgically delivered day-20 foetuses, the cyclic AMP concentration increased for a least two hours. Glucagon and epinephrine increases the hepatic cyclic AMP concentration in rats delivered surgically on days 20, 21 and 22 of gestation and in postnatal rats. Maximal stimulation by epinephrine was observed in 2-day-old rats. Maximal stimulation by glucagon was observed in 10-day-old rats. The results support the hypothesis that cyclic AMP is the intracellular effector for the synthesis of some enzymes in the perinatal rat. The cyclic AMP concentration in the perinatal rat liver in vivo appears to be controlled by changes in the relative concentrations of plasma glucagon and insulin.", "contents": "Adenosine 3':5'-monophosphate in perinatal rat liver. Ontogeny and response to hormones. Developmental changes in the concentration of adenosine 3':5'-monophosphate (cyclic AMP) and the effects of glucagon and epinephrine were studied in the perinatal rat liver. Hepatic cyclic AMP concentration doubled during the last day of gestation. After birth, the cyclic AMP concentration continued to increase and maximal levels were observed on the fifth postnatal day. Surgical delivery of foetuses on days 20, 21 and 22 of gestation resulted in a rapid increase in cyclic AMP concentration. Maximal concentrations were reached within one hour of delivery in the day-21 and day-22 foetuses. However with surgically delivered day-20 foetuses, the cyclic AMP concentration increased for a least two hours. Glucagon and epinephrine increases the hepatic cyclic AMP concentration in rats delivered surgically on days 20, 21 and 22 of gestation and in postnatal rats. Maximal stimulation by epinephrine was observed in 2-day-old rats. Maximal stimulation by glucagon was observed in 10-day-old rats. The results support the hypothesis that cyclic AMP is the intracellular effector for the synthesis of some enzymes in the perinatal rat. The cyclic AMP concentration in the perinatal rat liver in vivo appears to be controlled by changes in the relative concentrations of plasma glucagon and insulin."}
{"id": "PMID:208841", "title": "Identification of some metabolic products of 5' -deoxy-5' -S-isobutylthioadenosine, an inhibitor of virus-induced cell transformation.", "content": "5' -Deoxy-5' -S-isobutylthioadenosine (iBuS)5' Ado has been shown to be rapidly degraded to 5-deoxy-5-S-isobutylthioribose and adenine in procaryotes. In chick embryo fibroblasts there are two metabolic pathways for (iBuS)5' Ado degradation: (a) oxidative deamination into 5' -deoxy-5'-S-isobutylthioinosine (the main product) and (b) hydrolysis into 5-deoxy-5-S-isobutylthioribose plus adenine. The latter reaction is not due to bacterial contamination, since the same results were obtained under sterile conditions and in chick embryo fibroblasts in culture. The inhibition of the virus-induced cell transformation reported by us previously was due to (iBuS)5' Ado rather than to the main metabolic product of this molecule in chick embryo fibroblasts.", "contents": "Identification of some metabolic products of 5' -deoxy-5' -S-isobutylthioadenosine, an inhibitor of virus-induced cell transformation. 5' -Deoxy-5' -S-isobutylthioadenosine (iBuS)5' Ado has been shown to be rapidly degraded to 5-deoxy-5-S-isobutylthioribose and adenine in procaryotes. In chick embryo fibroblasts there are two metabolic pathways for (iBuS)5' Ado degradation: (a) oxidative deamination into 5' -deoxy-5'-S-isobutylthioinosine (the main product) and (b) hydrolysis into 5-deoxy-5-S-isobutylthioribose plus adenine. The latter reaction is not due to bacterial contamination, since the same results were obtained under sterile conditions and in chick embryo fibroblasts in culture. The inhibition of the virus-induced cell transformation reported by us previously was due to (iBuS)5' Ado rather than to the main metabolic product of this molecule in chick embryo fibroblasts."}
{"id": "PMID:208842", "title": "An intramolecularly quenched fluorescent tripeptide as a fluorogenic substrate of angiotensin-I-converting enzyme and of bacterial dipeptidyl carboxypeptidase.", "content": "The N-acyltripeptide 2-aminobenzoylglycyl-p-nitrophenylalanylproline was synthesized and applied as a substrate in the assay of angiotensin-I-converting enzyme from calf lung and human serum, and of the bacterial dipeptidyl carboxypeptidase from Escherichia coli. This compound belongs to a new class of substrates for proteolytic enzymes, having the general structure F--X--Q in which fluorescence of group F  is quenched by intramolecular interaction with the group Q. Enzymatic cleavage of the peptide chain (X stands for one or more amino acid residues) generates the unquenched F-containing derivative and the resulting fluorescence is used for quantitative measurement of the hydrolysis rate. Cleavage of the Gly-Phe(NO2) peptide bond in the weakly fluorescent 2-amino-benzoylglycyl-p-nitrophenylalanylproline molecule results in appearance of the 71 times higher fluorescence (lambdamax = 415 nm) of 2-aminobenzoylglycine. Continuous recording of the rising fluorescence allows convenient, sensitive and specific determination of the enzymatic activity, applicable to crude enzyme preparations and human serum. The activity of the mammalian enzyme, measured by this method, is enhanced by Cl- ions and inhibited by low concentrations of EDTA and [Asn1, Val5]angiotensin II. Kinetic measurements showed Michaelis-Menten behavior, Km = 0.21 +/- 0.1 mM and 0.16 +/- 0.1 mM for the calf lung and the bacterial enzyme respectively.", "contents": "An intramolecularly quenched fluorescent tripeptide as a fluorogenic substrate of angiotensin-I-converting enzyme and of bacterial dipeptidyl carboxypeptidase. The N-acyltripeptide 2-aminobenzoylglycyl-p-nitrophenylalanylproline was synthesized and applied as a substrate in the assay of angiotensin-I-converting enzyme from calf lung and human serum, and of the bacterial dipeptidyl carboxypeptidase from Escherichia coli. This compound belongs to a new class of substrates for proteolytic enzymes, having the general structure F--X--Q in which fluorescence of group F  is quenched by intramolecular interaction with the group Q. Enzymatic cleavage of the peptide chain (X stands for one or more amino acid residues) generates the unquenched F-containing derivative and the resulting fluorescence is used for quantitative measurement of the hydrolysis rate. Cleavage of the Gly-Phe(NO2) peptide bond in the weakly fluorescent 2-amino-benzoylglycyl-p-nitrophenylalanylproline molecule results in appearance of the 71 times higher fluorescence (lambdamax = 415 nm) of 2-aminobenzoylglycine. Continuous recording of the rising fluorescence allows convenient, sensitive and specific determination of the enzymatic activity, applicable to crude enzyme preparations and human serum. The activity of the mammalian enzyme, measured by this method, is enhanced by Cl- ions and inhibited by low concentrations of EDTA and [Asn1, Val5]angiotensin II. Kinetic measurements showed Michaelis-Menten behavior, Km = 0.21 +/- 0.1 mM and 0.16 +/- 0.1 mM for the calf lung and the bacterial enzyme respectively."}
{"id": "PMID:208844", "title": "The regulation of glycogen metabolism. Purification and characterisation of protein phosphatase inhibitor-1 from rabbit skeletal muscle.", "content": "Inhibitor-1  is a protein which inhibits phosphorylase phosphatase only when it has been phosphorylated by cyclic-AMP-dependent protein kinase [Huang, F. L. and Glinsmann, W. H. (1976) Eur. J. Biochem. 70, 419--426]. Inhibitor-1 was purified by a heat treatment at 90 degrees C, precipitation with ammonium sulphate, chromatography on DEAE-cellulose, gel filtration on Sephadex G-100, and finally rechromatography of the phosphorylated protein on DEAE-cellulose, The protein was purified 4000-fold and 1.5 mg per 1000 g muscle was obtained in seven days corresponding to an overall yield of 15-20%. The purified protein was in a state approaching homogeneity as judged by the criteria of polyacrylamide-gel electrophoresis and ultracentrifugal analysis. The concentration of inhibitor-1 in vivo was calculated to be 1.5 micron, which is at least as high as the concentration of phosphorylase phosphatase. The amino acid composition of inhibitor-1 showed several unusual features. Glutamic acid and proline accounted for nearly one third of the residues, tyrosine, tryptophan and cysteine were absent, and the content of aromatic amino acids was very low. The molecular weight measured by sedimentation equilibrium centrifugation was 19200 and by amino acid analysis was 20800. These values were lower than the mol. wt 26000 determined empirically by gel electrophoresis in the presence of sodium dodecyl sulphate, and much lower than the apparent molecular weight of 60000 estimated by gel filtration on Sephadex G-100. The gel filtration behaviour, stability to heating at 100 degrees C and amino acid composition suggest that inhibitor-1 may possess little ordered structure. The phosphorylated from of inhibitor-1 contained close to one molecule of covalently bound phosphate per mole of protein, which is consistent with the previous finding of a unique decapeptide sequence at the site of phosphorylation, Ile-Arg-Arg-Arg-Arg-Pro-Thr(P)-Pro-Ala-Thr- [Cohen, P., Rylatt, D. B. and Nimmo, G. A. (1977) FEBS Lett. 76, 182-186].the phosphorylated form of inhibitor-1 inhibited phosphorylase phosphatase activity (0.02U) by 50% at a concentration of only 7.0 nM in the standard assay, but the phosphorylated decapeptide was 1000-2000 times less effective as an inhibitor.", "contents": "The regulation of glycogen metabolism. Purification and characterisation of protein phosphatase inhibitor-1 from rabbit skeletal muscle. Inhibitor-1  is a protein which inhibits phosphorylase phosphatase only when it has been phosphorylated by cyclic-AMP-dependent protein kinase [Huang, F. L. and Glinsmann, W. H. (1976) Eur. J. Biochem. 70, 419--426]. Inhibitor-1 was purified by a heat treatment at 90 degrees C, precipitation with ammonium sulphate, chromatography on DEAE-cellulose, gel filtration on Sephadex G-100, and finally rechromatography of the phosphorylated protein on DEAE-cellulose, The protein was purified 4000-fold and 1.5 mg per 1000 g muscle was obtained in seven days corresponding to an overall yield of 15-20%. The purified protein was in a state approaching homogeneity as judged by the criteria of polyacrylamide-gel electrophoresis and ultracentrifugal analysis. The concentration of inhibitor-1 in vivo was calculated to be 1.5 micron, which is at least as high as the concentration of phosphorylase phosphatase. The amino acid composition of inhibitor-1 showed several unusual features. Glutamic acid and proline accounted for nearly one third of the residues, tyrosine, tryptophan and cysteine were absent, and the content of aromatic amino acids was very low. The molecular weight measured by sedimentation equilibrium centrifugation was 19200 and by amino acid analysis was 20800. These values were lower than the mol. wt 26000 determined empirically by gel electrophoresis in the presence of sodium dodecyl sulphate, and much lower than the apparent molecular weight of 60000 estimated by gel filtration on Sephadex G-100. The gel filtration behaviour, stability to heating at 100 degrees C and amino acid composition suggest that inhibitor-1 may possess little ordered structure. The phosphorylated from of inhibitor-1 contained close to one molecule of covalently bound phosphate per mole of protein, which is consistent with the previous finding of a unique decapeptide sequence at the site of phosphorylation, Ile-Arg-Arg-Arg-Arg-Pro-Thr(P)-Pro-Ala-Thr- [Cohen, P., Rylatt, D. B. and Nimmo, G. A. (1977) FEBS Lett. 76, 182-186].the phosphorylated form of inhibitor-1 inhibited phosphorylase phosphatase activity (0.02U) by 50% at a concentration of only 7.0 nM in the standard assay, but the phosphorylated decapeptide was 1000-2000 times less effective as an inhibitor."}
{"id": "PMID:208845", "title": "The regulation of glycogen metabolism. Phosphorylation of inhibitor-1 from rabbit skeletal muscle, and its interaction with protein phosphatases-III and -II.", "content": "Inhibitor-1 from rabbit skeletal muscle was phosphorylated by protein kinase dependent on adenosine 3' :5'-monophosphate (cyclic AMP), but not by phosphorylase kinase or by glycogen synthetase kinase-2. Protein phosphatase-III, isolated and stored in the presence of manganese ions to keep it stable, was in a form which catalysed a rapid dephosphorylation and inactivation of inhibitor-1. The kinetic constants for the dephosphorylation of inhibitor-1 [Km = 0.7 micron, V(rel) = 40] were comparable to those for the dephosphorylation of phosphorylase kinase [Km =1.1 micron, V (rel) = 62] and phosphorylase [Km = 5.0 micron, V (rel) = 100]. The dephosphorylation of inhibitor -1 was inhibited by inhibitor-2, indicating that it was catalysed by protein phosphatase-III, and not by another enzyme that might be contaminating the preparation. When protein phosphatase-III was diluted into buffers containing excess EDTA, it lost activity initially, but after 90 min, the activity reached a plateau that remained stable for at least 20h. The initial loss in activity varied with the substrate that was tested; it was 20-30% with phosphorylase a, 50-60% with phosphorylase kinase and greater than or equal to 95% with inhibitor-1. This form of protein phosphatase-III was inhibited by inhibitor-1 in a noncompetitive manner, and the Ki for inhibitor-1 was 1.6 +/- 0.3 nM. The phosphorylase phosphatase, phosphorylase kinase phosphatase and glycogen synthetase phosphatase activities of protein phosphatase-III were inhibited in an identical manner by inhibitor-1. This result emphasizes the potential importance of inhibitor-1 in the regulation of glycogen metabolism, since it can influence the state of phosphorylation of three different enzymes. The formation of the inactive complex between inhibitor-1 and protein phosphatase-III was reversed by incubation with trypsin (which destroyed inhibitor-1, but not protein phosphatase-III) or by dilution of the inactive complex. Kinetic studies, using the form of protein phosphatase-III which dephosphorylated inhibitor-1 very rapidly, demonstrated three unusual features of the system: (a) inhibitor-1 was still as powerful and inhibitor of the dephosphorylation of phosphorylase a and phosphorylase kinase a even under conditions where it was being rapidly dephosphorylated; (b) inhibitor-1 was not an inhibitor of its own dephosphorylation; (c) phosphorylase a did not effect the rate of dephosphorylation of inhibitor-1 even when it was present in a 50-fold molar excess over inhibitor-1. The result of these three properties is that inhibitor-1 is preferentially dephosphorylated by protein phosphatase-III even in the presence of a large excess of other phosphoprotein substrates. Inhibitor-1 was also dephosphorylated by protein phosphatase-II. The kinetic constants for the dephosphorylation of inhibitor-1 [Km = 2.8 micron, V (rel) = 200] and the alpha-subunit of phosphorylase kinase [Km = 3.7 micron, V (rel) = 100]were comparable...", "contents": "The regulation of glycogen metabolism. Phosphorylation of inhibitor-1 from rabbit skeletal muscle, and its interaction with protein phosphatases-III and -II. Inhibitor-1 from rabbit skeletal muscle was phosphorylated by protein kinase dependent on adenosine 3' :5'-monophosphate (cyclic AMP), but not by phosphorylase kinase or by glycogen synthetase kinase-2. Protein phosphatase-III, isolated and stored in the presence of manganese ions to keep it stable, was in a form which catalysed a rapid dephosphorylation and inactivation of inhibitor-1. The kinetic constants for the dephosphorylation of inhibitor-1 [Km = 0.7 micron, V(rel) = 40] were comparable to those for the dephosphorylation of phosphorylase kinase [Km =1.1 micron, V (rel) = 62] and phosphorylase [Km = 5.0 micron, V (rel) = 100]. The dephosphorylation of inhibitor -1 was inhibited by inhibitor-2, indicating that it was catalysed by protein phosphatase-III, and not by another enzyme that might be contaminating the preparation. When protein phosphatase-III was diluted into buffers containing excess EDTA, it lost activity initially, but after 90 min, the activity reached a plateau that remained stable for at least 20h. The initial loss in activity varied with the substrate that was tested; it was 20-30% with phosphorylase a, 50-60% with phosphorylase kinase and greater than or equal to 95% with inhibitor-1. This form of protein phosphatase-III was inhibited by inhibitor-1 in a noncompetitive manner, and the Ki for inhibitor-1 was 1.6 +/- 0.3 nM. The phosphorylase phosphatase, phosphorylase kinase phosphatase and glycogen synthetase phosphatase activities of protein phosphatase-III were inhibited in an identical manner by inhibitor-1. This result emphasizes the potential importance of inhibitor-1 in the regulation of glycogen metabolism, since it can influence the state of phosphorylation of three different enzymes. The formation of the inactive complex between inhibitor-1 and protein phosphatase-III was reversed by incubation with trypsin (which destroyed inhibitor-1, but not protein phosphatase-III) or by dilution of the inactive complex. Kinetic studies, using the form of protein phosphatase-III which dephosphorylated inhibitor-1 very rapidly, demonstrated three unusual features of the system: (a) inhibitor-1 was still as powerful and inhibitor of the dephosphorylation of phosphorylase a and phosphorylase kinase a even under conditions where it was being rapidly dephosphorylated; (b) inhibitor-1 was not an inhibitor of its own dephosphorylation; (c) phosphorylase a did not effect the rate of dephosphorylation of inhibitor-1 even when it was present in a 50-fold molar excess over inhibitor-1. The result of these three properties is that inhibitor-1 is preferentially dephosphorylated by protein phosphatase-III even in the presence of a large excess of other phosphoprotein substrates. Inhibitor-1 was also dephosphorylated by protein phosphatase-II. The kinetic constants for the dephosphorylation of inhibitor-1 [Km = 2.8 micron, V (rel) = 200] and the alpha-subunit of phosphorylase kinase [Km = 3.7 micron, V (rel) = 100]were comparable..."}
{"id": "PMID:208846", "title": "Occurrence of two fucosyltransferase activities at the outer surface of rat lymphocytes.", "content": "To demonstrate the existence of ectofucosyltransferase activities on the outer surface of rat lymphocytes, we measured fucosyltransferase activities on whole cells using procedures enabling us to exclude the possibility of misleading results due to precursor hydrolysis and intracellular utilization of the free fucose, and to take into account the contamination by intracellular enzymes freed by the small percentage of broken cells. The described ectofucosyltransferases are able to catalyze the transfer of fucosyl residues from GDP-fucose to the endogenous membrane acceptors but the transfer activity towards exogenous acceptors is restricted to low molecular weight compounds. Use of galactose and di-N-acetylchitobiose as exogenous acceptors and concomitant study of the specific inhibition by N-ethylmaleimide enabled us to detect both types of ectofucosyltransferases: a GDP-fucose: galactoside ectofucosyltransferase and a GDP-fucose: N-acetylglucosaminide ectofucosyltransferase.", "contents": "Occurrence of two fucosyltransferase activities at the outer surface of rat lymphocytes. To demonstrate the existence of ectofucosyltransferase activities on the outer surface of rat lymphocytes, we measured fucosyltransferase activities on whole cells using procedures enabling us to exclude the possibility of misleading results due to precursor hydrolysis and intracellular utilization of the free fucose, and to take into account the contamination by intracellular enzymes freed by the small percentage of broken cells. The described ectofucosyltransferases are able to catalyze the transfer of fucosyl residues from GDP-fucose to the endogenous membrane acceptors but the transfer activity towards exogenous acceptors is restricted to low molecular weight compounds. Use of galactose and di-N-acetylchitobiose as exogenous acceptors and concomitant study of the specific inhibition by N-ethylmaleimide enabled us to detect both types of ectofucosyltransferases: a GDP-fucose: galactoside ectofucosyltransferase and a GDP-fucose: N-acetylglucosaminide ectofucosyltransferase."}
{"id": "PMID:208848", "title": "Protein kinases of rat liver endoplasmic reticulum. Solubilisation, partial characterisation and comparison with protein kinases of rat liver cytosol.", "content": "Protein kinase associated with rat liver microsomes was only partly extracted by treatment with 1.5 M KCl. The enzyme was solubilised by Triton X-100 or sodium deoxycholate at the same or slightly higher detergent concentrations than microsomal marker components. The enzyme activity increased 2-3 fold upon solubilisation. Three peaks with protein kinase activity (fractions MI, MII and MIII) were resolved on DEAE-cellulose chromatography. Fraction MIII but not fractions MI or MII was activated by adenosine 3':5'-monophosphate (cyclic AMP). All fractions catalysed the phosphorylation of protamine and histones but not that of casein or phosvitin. Fractions MI and MIII had a similar substrate specificity and phosphorylated histones at a relatively much higher rate than did fraction MII. The isoelectric points were 8.1 for fraction MI, 5.5 for fraction MII and 4.9 for fraction MIII. On incubation of fraction MIII with cyclic AMP it was split into two catalytically active components with pI 8.1 and 7.35. The component with pI 8.1 was predominant and corresponded to fraction MI. Five protein kinase peaks were resolved from rat liver cytosol by DEAE-cellulose chromatography. Three of them (fractions CIa, CIIb and CIII) had the same properties as each of the microsomal kinase fractions.  A forth fraction (CIIa) was cyclic-AMP-dependent and had the same substrate specificity as fractions MI and MIII. Its pI was 5.1, and it was split into two components by cyclic AMP (pI 8.1 and 7.35). In binding studies fraction CIIb bound more efficiently to microsomes than fraction CIII, while fractions CIa, CIIa and the microsomal protein kinase fractions did not bind appreciably. When microsomes were treated with trypsin exposed protein kinase was inactivated and the latency of the remaining enzyme increased substantially. Most of fraction MII was inactivated by trypsin while fraction MIII was resistant. The possible orientation of protein kinase fractions MII and MIII in the microsomal membrane is discussed.", "contents": "Protein kinases of rat liver endoplasmic reticulum. Solubilisation, partial characterisation and comparison with protein kinases of rat liver cytosol. Protein kinase associated with rat liver microsomes was only partly extracted by treatment with 1.5 M KCl. The enzyme was solubilised by Triton X-100 or sodium deoxycholate at the same or slightly higher detergent concentrations than microsomal marker components. The enzyme activity increased 2-3 fold upon solubilisation. Three peaks with protein kinase activity (fractions MI, MII and MIII) were resolved on DEAE-cellulose chromatography. Fraction MIII but not fractions MI or MII was activated by adenosine 3':5'-monophosphate (cyclic AMP). All fractions catalysed the phosphorylation of protamine and histones but not that of casein or phosvitin. Fractions MI and MIII had a similar substrate specificity and phosphorylated histones at a relatively much higher rate than did fraction MII. The isoelectric points were 8.1 for fraction MI, 5.5 for fraction MII and 4.9 for fraction MIII. On incubation of fraction MIII with cyclic AMP it was split into two catalytically active components with pI 8.1 and 7.35. The component with pI 8.1 was predominant and corresponded to fraction MI. Five protein kinase peaks were resolved from rat liver cytosol by DEAE-cellulose chromatography. Three of them (fractions CIa, CIIb and CIII) had the same properties as each of the microsomal kinase fractions.  A forth fraction (CIIa) was cyclic-AMP-dependent and had the same substrate specificity as fractions MI and MIII. Its pI was 5.1, and it was split into two components by cyclic AMP (pI 8.1 and 7.35). In binding studies fraction CIIb bound more efficiently to microsomes than fraction CIII, while fractions CIa, CIIa and the microsomal protein kinase fractions did not bind appreciably. When microsomes were treated with trypsin exposed protein kinase was inactivated and the latency of the remaining enzyme increased substantially. Most of fraction MII was inactivated by trypsin while fraction MIII was resistant. The possible orientation of protein kinase fractions MII and MIII in the microsomal membrane is discussed."}
{"id": "PMID:208850", "title": "Vascular origin of Poland syndrome? A comparative rheographic study of the vascularisation of the arms in eight patients.", "content": "Vascularization of the arms has been studied by impedance plethysmography (rheography) in eight children with Poland syndrome, a common malformation characterized by unilateral hand anomaly and ipsilateral aplasia of the inferior head of the pectoralis major muscle. A marked decrease of the velocity of the systolic increase in the arterial volume (Velm) was shown in the affected arms, and the difference between the two arms was significantly higher in the patients than in a control group (P less than 0.02). These results, which are also observed in stenotic atherosclerosis, support the hypothesis of hypoplasia of the ipsilateral subclavian artery as the origin of the malformation, although a local anomaly in arterial-wall viscosity cannot be ruled out. The opacification of the aortic arch in another patient confirmed this hypothesis. Aortography in further patients will be necessary to substantiate our results. However, this technique is not without danger and should only be used during the first months of life when a vascular operation can be envisaged.", "contents": "Vascular origin of Poland syndrome? A comparative rheographic study of the vascularisation of the arms in eight patients. Vascularization of the arms has been studied by impedance plethysmography (rheography) in eight children with Poland syndrome, a common malformation characterized by unilateral hand anomaly and ipsilateral aplasia of the inferior head of the pectoralis major muscle. A marked decrease of the velocity of the systolic increase in the arterial volume (Velm) was shown in the affected arms, and the difference between the two arms was significantly higher in the patients than in a control group (P less than 0.02). These results, which are also observed in stenotic atherosclerosis, support the hypothesis of hypoplasia of the ipsilateral subclavian artery as the origin of the malformation, although a local anomaly in arterial-wall viscosity cannot be ruled out. The opacification of the aortic arch in another patient confirmed this hypothesis. Aortography in further patients will be necessary to substantiate our results. However, this technique is not without danger and should only be used during the first months of life when a vascular operation can be envisaged."}
{"id": "PMID:208851", "title": "The effect of cyproterone acetate on adrenal cortical function in children with precocious puberty.", "content": "8 children with precocious puberty were treated with cyproterone acetate (CPA). During treatment there were no definite clinical signs of depressed adrenocortical function. The plasma cortisol concentrations were grossly depressed and the diurnal cortisol rhythm was abolished. Two months after discontinuation of CPA treatment the adrenocortical function had greatly improved. The lysin-vasopressin stimulation test revealed in one child a normal, in another child an exaggerated ACTH response during CPA therapy. Fasting plasma ACTH concentrations were elevated compared with normal controls, but they were very low compared with patients with Addison's disease. The results suggest that CPA has a twofold effect leading to adrenocortical insufficiency: i.e., inhibition of cortisol secretion by the adrenals themselves and inhibition of ACTH secretion at the hypothalamopitiuitary level.", "contents": "The effect of cyproterone acetate on adrenal cortical function in children with precocious puberty. 8 children with precocious puberty were treated with cyproterone acetate (CPA). During treatment there were no definite clinical signs of depressed adrenocortical function. The plasma cortisol concentrations were grossly depressed and the diurnal cortisol rhythm was abolished. Two months after discontinuation of CPA treatment the adrenocortical function had greatly improved. The lysin-vasopressin stimulation test revealed in one child a normal, in another child an exaggerated ACTH response during CPA therapy. Fasting plasma ACTH concentrations were elevated compared with normal controls, but they were very low compared with patients with Addison's disease. The results suggest that CPA has a twofold effect leading to adrenocortical insufficiency: i.e., inhibition of cortisol secretion by the adrenals themselves and inhibition of ACTH secretion at the hypothalamopitiuitary level."}
{"id": "PMID:208852", "title": "Chronic Niemann-Pick disease with sphingomyelinase deficiency in two brothers with mental retardation.", "content": "Clinical, biochemical, and electron microscopic studies are presented in two brothers with Niemann-Pick disease. The clinical features include hepatosplenomegaly and mental retardation without any other neurological signs. Roentgenograms of the chest showed bilateral diffuse reticular infiltration. The amounts of sphingomyelin and cholesterol in liver were increased, and sphingomyelinase activities in both liver and skin fibroblasts were markedly reduced in Case 1. Numerous foam cells and myelin figures were observed in the liver, kidneys, bone marrow, and lymph nodes on electron microscopical examination. These cases were regarded as a variant of Niemann-Pick disease from our investigations as they have mental retardation as an exceptional symptom when they are diagnosed as type B.", "contents": "Chronic Niemann-Pick disease with sphingomyelinase deficiency in two brothers with mental retardation. Clinical, biochemical, and electron microscopic studies are presented in two brothers with Niemann-Pick disease. The clinical features include hepatosplenomegaly and mental retardation without any other neurological signs. Roentgenograms of the chest showed bilateral diffuse reticular infiltration. The amounts of sphingomyelin and cholesterol in liver were increased, and sphingomyelinase activities in both liver and skin fibroblasts were markedly reduced in Case 1. Numerous foam cells and myelin figures were observed in the liver, kidneys, bone marrow, and lymph nodes on electron microscopical examination. These cases were regarded as a variant of Niemann-Pick disease from our investigations as they have mental retardation as an exceptional symptom when they are diagnosed as type B."}
{"id": "PMID:208855", "title": "Free radical intermediates produced by autoxidation of 1,8-dihydroxy-9-anthrone (dithranol) in pyridine.", "content": "The autoxidation of the antipsoriatic agent dithranol, monitored by an ESR-spectrometer, proceeds through several free radical intermediates. The initial radical, attacking a bulky spin trapping agent in a sterically comparatively hindered constellation, may be the active therapeutic form of dithranol.", "contents": "Free radical intermediates produced by autoxidation of 1,8-dihydroxy-9-anthrone (dithranol) in pyridine. The autoxidation of the antipsoriatic agent dithranol, monitored by an ESR-spectrometer, proceeds through several free radical intermediates. The initial radical, attacking a bulky spin trapping agent in a sterically comparatively hindered constellation, may be the active therapeutic form of dithranol."}
{"id": "PMID:208856", "title": "Electronmicroscopic identification of type C particles in cultured murine neuroblastoma.", "content": "Monolayer of murine neuroblastoma were treated with dexamethasone and examined by electronmicroscopy. Most of the treated cells were morphologically differentiated and exhibited type C virus particles which were budding from the cell surface. This in vitro system may be of great value for exploring the oncogenic potential of the virus, and its possible role in cell differentiation.", "contents": "Electronmicroscopic identification of type C particles in cultured murine neuroblastoma. Monolayer of murine neuroblastoma were treated with dexamethasone and examined by electronmicroscopy. Most of the treated cells were morphologically differentiated and exhibited type C virus particles which were budding from the cell surface. This in vitro system may be of great value for exploring the oncogenic potential of the virus, and its possible role in cell differentiation."}
{"id": "PMID:208859", "title": "[The effect of curare-like agents on synaptic transmission in the spinal cord].", "content": "In experiments with decerebrated cats subject to study was the influence of new curare-like agents of non-depolarized type of action, such as diadonium, decadonium, RGH-1106, pancuronium-bromide (pavulon) and also of paramion and mellictine on the magnitude of mono-and polysynaptic potentials of the spinal cord, the time of synaptic delay, the lability of the spinal centres and cycle of the motoneurons excitability restoration. Diadonium, decadonium, RGH-1106 and pavulon when used in 1--5-fold myoparalytic doses did not affect the bioelectric activity of the spinal cord. Mellictinum (3,5--4,5 mg/kg)) produced a rise of the monosynaptic responses amplitude by 21 per cent through inhibition of the Renshow n-cholinoreceptors cells. Paramion (0.3--1 mg/kg) suppressed monosynaptic potentials, increasing the afferent proprioceptic activity.", "contents": "[The effect of curare-like agents on synaptic transmission in the spinal cord]. In experiments with decerebrated cats subject to study was the influence of new curare-like agents of non-depolarized type of action, such as diadonium, decadonium, RGH-1106, pancuronium-bromide (pavulon) and also of paramion and mellictine on the magnitude of mono-and polysynaptic potentials of the spinal cord, the time of synaptic delay, the lability of the spinal centres and cycle of the motoneurons excitability restoration. Diadonium, decadonium, RGH-1106 and pavulon when used in 1--5-fold myoparalytic doses did not affect the bioelectric activity of the spinal cord. Mellictinum (3,5--4,5 mg/kg)) produced a rise of the monosynaptic responses amplitude by 21 per cent through inhibition of the Renshow n-cholinoreceptors cells. Paramion (0.3--1 mg/kg) suppressed monosynaptic potentials, increasing the afferent proprioceptic activity."}
{"id": "PMID:208858", "title": "[Possible concentration-dependent mechanism of action exerted by epinephrine on giant neurons].", "content": "The results of an investigation carried out suggest that both the stimulating and inhibitory action of epinephrine on the neuronal activity are mediated by the adenylate-cyclase system. The reason of the effect of epinephrine depending on its concentration is, apparantly, the polyfunctionality of the \"second mediator\"--cAMP and the primordial existence in the cells of processes oppositely influencing its functional activity, whose intensity depends on the concentration of cAMP.", "contents": "[Possible concentration-dependent mechanism of action exerted by epinephrine on giant neurons]. The results of an investigation carried out suggest that both the stimulating and inhibitory action of epinephrine on the neuronal activity are mediated by the adenylate-cyclase system. The reason of the effect of epinephrine depending on its concentration is, apparantly, the polyfunctionality of the \"second mediator\"--cAMP and the primordial existence in the cells of processes oppositely influencing its functional activity, whose intensity depends on the concentration of cAMP."}
{"id": "PMID:208873", "title": "Inhibitory effect of a luteinizing hormone (LH)-releasing hormone agonist on rat ovarian LH and follicle-stimulating hormone receptor levels during pregnancy.", "content": "When injected at the daily dose of 100 microgram on days 7 through 12 of pregnancy, the luteinizing hormone (LH)-releasing hormone (LHRH) agonist [D-Ala6, des-Gly-NH2(10)] LHRH ethylamide led to complete suppression of pregnancy and a 45% to 60% decrease in plasma progesterone concentration. The antifertility effect of the LHRH analog was accompanied by an early and almost complete inhibition of ovarian LH/human chorionic gonadotropin and follicle-stimulating hormone receptor levels. These data suggest that the antifertility effects of LHRH agonists are mediated by down-regulation of ovarian gonadotropin receptors and decreased luteal function.", "contents": "Inhibitory effect of a luteinizing hormone (LH)-releasing hormone agonist on rat ovarian LH and follicle-stimulating hormone receptor levels during pregnancy. When injected at the daily dose of 100 microgram on days 7 through 12 of pregnancy, the luteinizing hormone (LH)-releasing hormone (LHRH) agonist [D-Ala6, des-Gly-NH2(10)] LHRH ethylamide led to complete suppression of pregnancy and a 45% to 60% decrease in plasma progesterone concentration. The antifertility effect of the LHRH analog was accompanied by an early and almost complete inhibition of ovarian LH/human chorionic gonadotropin and follicle-stimulating hormone receptor levels. These data suggest that the antifertility effects of LHRH agonists are mediated by down-regulation of ovarian gonadotropin receptors and decreased luteal function."}
{"id": "PMID:208874", "title": "Study of group-specific proteins in mammalian cells transformed by Rous sarcoma virus.", "content": "Lysates of various mammalian RSV-transformed cells labelled with 35S-methionine were tested for the presence of gs proteins and for the size of these molecules by means of antisera, using sodium dodecyl sulphate--polyacrylamide slab gel electrophoresis. In no case was the presence of gs proteins detected in the analyzed immunoprecipitates; only in RSH-mix cells a quantitative difference in the contrast of a 70 000-molecular weight protein was found. The autoradiograms of simultaneously tested immunoprecipitates of lysates of RSV-transformed chicken cells clearly showed the presence of p27 and after a short-term labelling also of the gs precursor molecule (pr76). The cause of the failure in detecting gs proteins by the used method in two mammalian RSV-transformed lines, in which the gs antigens were previously detected by complement fixation test, are discussed.", "contents": "Study of group-specific proteins in mammalian cells transformed by Rous sarcoma virus. Lysates of various mammalian RSV-transformed cells labelled with 35S-methionine were tested for the presence of gs proteins and for the size of these molecules by means of antisera, using sodium dodecyl sulphate--polyacrylamide slab gel electrophoresis. In no case was the presence of gs proteins detected in the analyzed immunoprecipitates; only in RSH-mix cells a quantitative difference in the contrast of a 70 000-molecular weight protein was found. The autoradiograms of simultaneously tested immunoprecipitates of lysates of RSV-transformed chicken cells clearly showed the presence of p27 and after a short-term labelling also of the gs precursor molecule (pr76). The cause of the failure in detecting gs proteins by the used method in two mammalian RSV-transformed lines, in which the gs antigens were previously detected by complement fixation test, are discussed."}
{"id": "PMID:208877", "title": "The use of cytochalasins in studies on the molecular biology of virus--host cell interactions.", "content": "In conclusion, one can say that the cytochalasins--in their brief history of application in virology--have proven to be valuable tools in studies on the molecular biology of virus--host cell interactions. On the other hand, viral systems can be useful in defining the primary sites of action of cytochalasins in certain cells. In interpreting the effects of cytochalasins on virus replication, however, one must take into consideration that the cytochalasins exert a wide variety of alterations in cellular functions. Infections by viruses interfere primarily with the synthesis of host DNA, RNA, and proteins. The experiments reviewed here were carried out with different viruses, different cell lines, and--more important--under very different experimental conditions. Nevertheless, a number of informative observations emerge which provide insight into specific aspects of the interaction of viruses with their host cells, and help us to understand the mode of action of cytochalasins on specific cellular functions: Cytochalasins may decrease or increase the competence of cells for infection by viruses. For the DNA viruses, vaccinia virus and adenovirus, cytochalasin treatment of host cells resulted in a reduced virus yield; whereas for the RNA viruses, poliovirus, parainfluenza virus, and VSV, cytochalasin treatment results in an increased virus yield. The precise mechanism by which cytochalasins exert these effects remain unclear. It is proposed that the cytochalasin-mediated enhancement of cell infectibility for poliovirus--the only system for which this effect has been studied in more detail--is primarily due to a reduction of polypeptide chain initiation. This reduction dramatically amplifies the inherent translational advantage of virus mRNAs over host cell mRNAs, resulting in a relative stimulation of viral mRNA translation. The cytochalasin-mediated sensitization of cells for infection by isolated poliovirus RNA is explainable by a comparable effect on protein synthesis. In this case, cytochalasin may act in part by substituting for the function of a viral protein(s). When cytochalasin B is added to cells which have previously been infected by intact HSV, formation of infectious virus particles is severely inhibited...", "contents": "The use of cytochalasins in studies on the molecular biology of virus--host cell interactions. In conclusion, one can say that the cytochalasins--in their brief history of application in virology--have proven to be valuable tools in studies on the molecular biology of virus--host cell interactions. On the other hand, viral systems can be useful in defining the primary sites of action of cytochalasins in certain cells. In interpreting the effects of cytochalasins on virus replication, however, one must take into consideration that the cytochalasins exert a wide variety of alterations in cellular functions. Infections by viruses interfere primarily with the synthesis of host DNA, RNA, and proteins. The experiments reviewed here were carried out with different viruses, different cell lines, and--more important--under very different experimental conditions. Nevertheless, a number of informative observations emerge which provide insight into specific aspects of the interaction of viruses with their host cells, and help us to understand the mode of action of cytochalasins on specific cellular functions: Cytochalasins may decrease or increase the competence of cells for infection by viruses. For the DNA viruses, vaccinia virus and adenovirus, cytochalasin treatment of host cells resulted in a reduced virus yield; whereas for the RNA viruses, poliovirus, parainfluenza virus, and VSV, cytochalasin treatment results in an increased virus yield. The precise mechanism by which cytochalasins exert these effects remain unclear. It is proposed that the cytochalasin-mediated enhancement of cell infectibility for poliovirus--the only system for which this effect has been studied in more detail--is primarily due to a reduction of polypeptide chain initiation. This reduction dramatically amplifies the inherent translational advantage of virus mRNAs over host cell mRNAs, resulting in a relative stimulation of viral mRNA translation. The cytochalasin-mediated sensitization of cells for infection by isolated poliovirus RNA is explainable by a comparable effect on protein synthesis. In this case, cytochalasin may act in part by substituting for the function of a viral protein(s). When cytochalasin B is added to cells which have previously been infected by intact HSV, formation of infectious virus particles is severely inhibited..."}
{"id": "PMID:208880", "title": "The effect of different regimens of oestrogens on the clotting and fibrinolytic system of the post-menopausal woman.", "content": "The effects of six different regimens of hormone replacement therapy on coagulation, fibrinolysis and platelet aggregation were sudied in 33 symptomatic, post-menopausal women. Studies were performed before and after 3 months of therapy in the six treatment groups, Premarin, Progynova, Harmogen, Serial 28, ethynodiol diacetate and a testosterone and oestradiol implant. No changes in any parameter were detected following administration of Premarin, Progynova or an implant of testosterone and oestradiol. Serial 28 produced a significant increase in plasminogen concentration and increased the extent of platelet aggregation in 0.5 micron adrenalin solution. Harmogen produced an increase in the extent of platelet aggregation in 1.0 micron adrenalin solution, but a decrease in the rate of platelet aggregation in 1.0 micron solution. Ethynodiol diacetate caused a significant decrease in the kaolin-cephalin clotting time but decreased the extent of platelet aggregation in 0.5 and 1.0 micron solutions of adrenalin. FDPs developed following therapy in 9 of the 33 patients. These were evenly distributed between the groups. No patients had any change in anti-Xa concentration, platelet count or platelet aggregation in thrombin.", "contents": "The effect of different regimens of oestrogens on the clotting and fibrinolytic system of the post-menopausal woman. The effects of six different regimens of hormone replacement therapy on coagulation, fibrinolysis and platelet aggregation were sudied in 33 symptomatic, post-menopausal women. Studies were performed before and after 3 months of therapy in the six treatment groups, Premarin, Progynova, Harmogen, Serial 28, ethynodiol diacetate and a testosterone and oestradiol implant. No changes in any parameter were detected following administration of Premarin, Progynova or an implant of testosterone and oestradiol. Serial 28 produced a significant increase in plasminogen concentration and increased the extent of platelet aggregation in 0.5 micron adrenalin solution. Harmogen produced an increase in the extent of platelet aggregation in 1.0 micron adrenalin solution, but a decrease in the rate of platelet aggregation in 1.0 micron solution. Ethynodiol diacetate caused a significant decrease in the kaolin-cephalin clotting time but decreased the extent of platelet aggregation in 0.5 and 1.0 micron solutions of adrenalin. FDPs developed following therapy in 9 of the 33 patients. These were evenly distributed between the groups. No patients had any change in anti-Xa concentration, platelet count or platelet aggregation in thrombin."}
{"id": "PMID:208883", "title": "[A clinical study on the effect of extrinsic corticotropin on the pituitary-adrenocortical function (author's transl)].", "content": "The effects of ACTH preparations on the pituitary-adrenocortical function remain to be clarified in more respects than those of steroid drugs. In the present study, the author investigated the effect of synthetic ACTH-Z on the pituitary-adrenocortical function in a series of 76 patients under synthetic ACTH-Z therapy using the daily urinary excretion of 17-KGS as an index. The results are summarized as follows: 1) The administration of synthetic ACTH-Z in a dose of 0.25 mg or 0.5 mg q.d. was followed by a gradually declining tendency of the daily urinary excretion of 17-KGS. More particularly, after 1.5 months of synthetic ACTH-Z medication at either of these dosage levels, the response of urinary 17-KGS was found to have decreased to about 1/2 of its level at the beginning of medication. 2) The responsiveness of urinary 17-KGS was well maintained even after 3 months of intermittent doses of 0.25 mg of synthetic ACTH-Z (3 times a week, or every other day). 3) Synthetic ACTH-Z, when used in a smaller dose of 0.125 mg daily, produced a minimal stimulating effect on the adrenal cortex. When administered in a less frequent (twice weekly) dose of 0.25 mg, synthetic ACTH-Z failed to prevent or counterbalance atrophy of the adrenal cortex induced by small doses of steroid drugs (average total dose equivalent to 12.2 mg of prednisolone). 4) With the purpose of activating the steroid-atrophied adrenal cortex, synthetic ACTH-Z was administered in a daily or intermittent (every other day, or 3 times a week) dose of 0.25 mg. With the daily dosage regimen, the atrophied adrenal cortex temporarily exhibited a good response, but its responsiveness soon decreased again, and in the end, synthetic ACTH-Z administered in this mode failed to activate the adrenal cortex. With the intermittent dosage regimen, on the other hand, a tendency toward recovery of adrenocortical responsiveness was observed in half the cases studied. In the remaining half receiving steroids over a prolonged period of time, recovery of adrenocortical responsiveness was not attained to any appreciable extent. These results might be interpreted as suggesting that the administration of synthetic ACTH-Z in an intermittent dose of 0.25 mg or 0.5 mg is advisable for the activation of the atrophied adrenal cortex. If this therapeutic regimen fails to initiate a tendency to recovery of adrenocortical responsiveness in a matter of a month or two, this implies that there is atrophy of the adrenal cortex severe enough to invalidate the therapeutic use of synthetic ACTH-Z. 5) The response of the adrenal cortex of 0.25 mg doses of synthetic ACTH-Z was distinctly suppressed by the concomitant use of steroids in 10 mg doses (as calculated on a prednisolone basis). Likewise, the response of the adrenal cortex of 0.5 mg doses of synthetic ACTH-Z was suppressed to 78%, 46% and 16%, respectively, by the conjoined use of steroids in doses of 20 mg, 30 mg and 40 mg or above...", "contents": "[A clinical study on the effect of extrinsic corticotropin on the pituitary-adrenocortical function (author's transl)]. The effects of ACTH preparations on the pituitary-adrenocortical function remain to be clarified in more respects than those of steroid drugs. In the present study, the author investigated the effect of synthetic ACTH-Z on the pituitary-adrenocortical function in a series of 76 patients under synthetic ACTH-Z therapy using the daily urinary excretion of 17-KGS as an index. The results are summarized as follows: 1) The administration of synthetic ACTH-Z in a dose of 0.25 mg or 0.5 mg q.d. was followed by a gradually declining tendency of the daily urinary excretion of 17-KGS. More particularly, after 1.5 months of synthetic ACTH-Z medication at either of these dosage levels, the response of urinary 17-KGS was found to have decreased to about 1/2 of its level at the beginning of medication. 2) The responsiveness of urinary 17-KGS was well maintained even after 3 months of intermittent doses of 0.25 mg of synthetic ACTH-Z (3 times a week, or every other day). 3) Synthetic ACTH-Z, when used in a smaller dose of 0.125 mg daily, produced a minimal stimulating effect on the adrenal cortex. When administered in a less frequent (twice weekly) dose of 0.25 mg, synthetic ACTH-Z failed to prevent or counterbalance atrophy of the adrenal cortex induced by small doses of steroid drugs (average total dose equivalent to 12.2 mg of prednisolone). 4) With the purpose of activating the steroid-atrophied adrenal cortex, synthetic ACTH-Z was administered in a daily or intermittent (every other day, or 3 times a week) dose of 0.25 mg. With the daily dosage regimen, the atrophied adrenal cortex temporarily exhibited a good response, but its responsiveness soon decreased again, and in the end, synthetic ACTH-Z administered in this mode failed to activate the adrenal cortex. With the intermittent dosage regimen, on the other hand, a tendency toward recovery of adrenocortical responsiveness was observed in half the cases studied. In the remaining half receiving steroids over a prolonged period of time, recovery of adrenocortical responsiveness was not attained to any appreciable extent. These results might be interpreted as suggesting that the administration of synthetic ACTH-Z in an intermittent dose of 0.25 mg or 0.5 mg is advisable for the activation of the atrophied adrenal cortex. If this therapeutic regimen fails to initiate a tendency to recovery of adrenocortical responsiveness in a matter of a month or two, this implies that there is atrophy of the adrenal cortex severe enough to invalidate the therapeutic use of synthetic ACTH-Z. 5) The response of the adrenal cortex of 0.25 mg doses of synthetic ACTH-Z was distinctly suppressed by the concomitant use of steroids in 10 mg doses (as calculated on a prednisolone basis). Likewise, the response of the adrenal cortex of 0.5 mg doses of synthetic ACTH-Z was suppressed to 78%, 46% and 16%, respectively, by the conjoined use of steroids in doses of 20 mg, 30 mg and 40 mg or above..."}
{"id": "PMID:208884", "title": "Silica toxicity for macrophages in vitro: a new cytotoxicity test.", "content": "Soluble factors released from silica-damaged macrophages inhibit proliferation of various haematopoietic cells in long term cultures. The same holds true for damage induced by heat, non-physiological pH, freezing and thawing. This phenomenon is dose-dependent and correlates with the degree of macrophage viability. Thus, a base for measuring the amount of damage to the macrophage is established.", "contents": "Silica toxicity for macrophages in vitro: a new cytotoxicity test. Soluble factors released from silica-damaged macrophages inhibit proliferation of various haematopoietic cells in long term cultures. The same holds true for damage induced by heat, non-physiological pH, freezing and thawing. This phenomenon is dose-dependent and correlates with the degree of macrophage viability. Thus, a base for measuring the amount of damage to the macrophage is established."}
{"id": "PMID:208885", "title": "Glucocorticoid modulation of adrenocorticotropin-induced melanogenesis in the Cloudman S-91 melanoma in vitro.", "content": "The acute in vitro action of adrenocorticotropin (ACTH) and corticosterone alone and in combination were determined in the Cloudman S-91 melanoma grown in vivo. Hormone-treated melanoma dice (5-240 min) were analyzed for tyrosinase activity (EC 1.14.18.1), cyclic AMP (cAMP) and cyclic GMP (cGMP). ACTH elevated cAMP levels in the S-91 melanoma. However, these increases in cAMP were not accompanied by increased tyrosinase activity. Corticosterone depressed cAMP levels while stimulating tyrosinase activity. ACTH plus corticosterone produced an early cAMP peak followed by depression. ACTH plus corticosterone stimulated tyrosine activity coincident with the early cAMP peak followed by a drop in tyrosinase activity which was subsequently elevated. cGMP levels were not altered by any hormone treatment. The results indicate that cAMP is not the sole modulator of tyrosinase activity and suggest the interaction of ACTH, corticosterone and cAMP in the regulation of melanoma tyrosinase activity.", "contents": "Glucocorticoid modulation of adrenocorticotropin-induced melanogenesis in the Cloudman S-91 melanoma in vitro. The acute in vitro action of adrenocorticotropin (ACTH) and corticosterone alone and in combination were determined in the Cloudman S-91 melanoma grown in vivo. Hormone-treated melanoma dice (5-240 min) were analyzed for tyrosinase activity (EC 1.14.18.1), cyclic AMP (cAMP) and cyclic GMP (cGMP). ACTH elevated cAMP levels in the S-91 melanoma. However, these increases in cAMP were not accompanied by increased tyrosinase activity. Corticosterone depressed cAMP levels while stimulating tyrosinase activity. ACTH plus corticosterone produced an early cAMP peak followed by depression. ACTH plus corticosterone stimulated tyrosine activity coincident with the early cAMP peak followed by a drop in tyrosinase activity which was subsequently elevated. cGMP levels were not altered by any hormone treatment. The results indicate that cAMP is not the sole modulator of tyrosinase activity and suggest the interaction of ACTH, corticosterone and cAMP in the regulation of melanoma tyrosinase activity."}
{"id": "PMID:208901", "title": "Speech, language and hearing in Moebius syndrome: a study of 22 patients.", "content": "A comprehensive profile of communicative disorders in patients with Moebius syndrome was attempted. Seven patients were evaluated by the authors and the findings were added to 15 contributed case-histories. Most patients demonstrated some degree of dysarthria due to congenital paralysis of the facial nerves. Other problems such as cleft palate, hearing loss, mental retardation and delayed development of language were found in a few of the patients. As most of the older children in the sample and in reports in the literature eventually developed intelligible speech, a program of oral language stimulation and compensatory articulatory adjustments would appear to be the procedure of choice.", "contents": "Speech, language and hearing in Moebius syndrome: a study of 22 patients. A comprehensive profile of communicative disorders in patients with Moebius syndrome was attempted. Seven patients were evaluated by the authors and the findings were added to 15 contributed case-histories. Most patients demonstrated some degree of dysarthria due to congenital paralysis of the facial nerves. Other problems such as cleft palate, hearing loss, mental retardation and delayed development of language were found in a few of the patients. As most of the older children in the sample and in reports in the literature eventually developed intelligible speech, a program of oral language stimulation and compensatory articulatory adjustments would appear to be the procedure of choice."}
{"id": "PMID:208903", "title": "The effect of induced hyperglucagonaemia on the Zucker fatty rat.", "content": "The effect of chronic treatment with a long-acting glucagon preparation on liver glucagon and insulin receptors, adenylate cyclase and plasma lipids has been examined in Zucker fatty rats (fa/fa) and their lean littermates (Fa/-). Liver insulin and glucagon receptors were examined using radioreceptor assay techniques. Neither fatty nor lean rats showed any change in insulin receptors after glucagon treatment. Glucagon receptors of the fatty rats showed a 33% drop in the number of the glucagon receptors after glucagon treatment, whilst there was no such change in the lean group. Plasma membranes of the treated fatty rats and their controls bound only 50% as much insulin per mg of liver membrane protein as those of the treated lean rats and their controls. Glucagon treatment raised plasma NEFA in lean rats and reduced them in fatty ones. Plasma cholesterol levels were reduced in both groups of animals as were plasma triglycerides, though to a lesser degree in fatty than in lean animals. Glucagon treatment increased basal and stimulated adenylate cyclase activity in the lean rats and even more so in the fatty ones. The data lend no support to the concept that hypertriglyceridaemia in fatty Zucker rats is a consequence of abnormal glucagon responsiveness.", "contents": "The effect of induced hyperglucagonaemia on the Zucker fatty rat. The effect of chronic treatment with a long-acting glucagon preparation on liver glucagon and insulin receptors, adenylate cyclase and plasma lipids has been examined in Zucker fatty rats (fa/fa) and their lean littermates (Fa/-). Liver insulin and glucagon receptors were examined using radioreceptor assay techniques. Neither fatty nor lean rats showed any change in insulin receptors after glucagon treatment. Glucagon receptors of the fatty rats showed a 33% drop in the number of the glucagon receptors after glucagon treatment, whilst there was no such change in the lean group. Plasma membranes of the treated fatty rats and their controls bound only 50% as much insulin per mg of liver membrane protein as those of the treated lean rats and their controls. Glucagon treatment raised plasma NEFA in lean rats and reduced them in fatty ones. Plasma cholesterol levels were reduced in both groups of animals as were plasma triglycerides, though to a lesser degree in fatty than in lean animals. Glucagon treatment increased basal and stimulated adenylate cyclase activity in the lean rats and even more so in the fatty ones. The data lend no support to the concept that hypertriglyceridaemia in fatty Zucker rats is a consequence of abnormal glucagon responsiveness."}
{"id": "PMID:208905", "title": "Experimental chemotherapy of carcinoma of the human stomach and colon serially transplanted in nude mice.", "content": "Human gastric and colon carcinomas serially transplantable in nude mice, designated as St-4, St-15, and Co-3, were used for chemotherapeutic experiments. All tumors showed a 100% take rate and stable growth. Mitomycin-C (MMC), 3 mg/kg body weight, given intraperitoneally 4 times once weekly, showed some inhibiting effect on Co-3, St-15, and St-4 in that order. N1-(2'-Tetrahydrofuryl)-5-fluorouracil (FT-207), 90 mg/kg body weight, intraperitoneally daily for 4 weeks, suppressed the growth of Co-3 and St-15 slightly but with statistical significance, and had no effect on St-4. Co-3, a tumor with more rapid growth and richer vascular supply, was suppressed more by MMC and FT-207. These three transplantable tumors may be useful, not only in evaluating chemotherapeutic agents for use against human gastrointestinal carcinomas, but also for screening of new antitumor agents.", "contents": "Experimental chemotherapy of carcinoma of the human stomach and colon serially transplanted in nude mice. Human gastric and colon carcinomas serially transplantable in nude mice, designated as St-4, St-15, and Co-3, were used for chemotherapeutic experiments. All tumors showed a 100% take rate and stable growth. Mitomycin-C (MMC), 3 mg/kg body weight, given intraperitoneally 4 times once weekly, showed some inhibiting effect on Co-3, St-15, and St-4 in that order. N1-(2'-Tetrahydrofuryl)-5-fluorouracil (FT-207), 90 mg/kg body weight, intraperitoneally daily for 4 weeks, suppressed the growth of Co-3 and St-15 slightly but with statistical significance, and had no effect on St-4. Co-3, a tumor with more rapid growth and richer vascular supply, was suppressed more by MMC and FT-207. These three transplantable tumors may be useful, not only in evaluating chemotherapeutic agents for use against human gastrointestinal carcinomas, but also for screening of new antitumor agents."}
{"id": "PMID:208906", "title": "Enhancing and inhibitory effects of some stilbene and steroid compounds on induction of hepatoma in rats fed 3'-methyl-4-(dimethylamino)azobenzene.", "content": "Examinations were made on substances that enhance or inhibit the induction of hepatoma in rats previously fed 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) for a brief period. The substances tested were stilbene, 4-nitrostilbene, 4,4'-dihydroxystilbene, diethylstilbestrol, 17beta-estradiol, and methyltestosterone. Male Donryu rats were fed 0.5 g of 3'-Me-DAB by being maintained on a diet containing 0.06% 3'-Me-DAB, and then they were fed 0.25 or 0.5 g of a test substance with the basal diet. Comparison of the development and yield of hepatomas indicated that 4-nitrostilbene and methyltestosterone had an activity of enhancing 3'-Me-DAB carcinogenesis, whereas diethylstilbestrol and 17beta-estradiol had an activity to retard it. Other substances showed no such activities. The enhancement by 4-nitrostilbene and inhibition by diethylstilbestrol of 3'-Me-DAB carcinogenesis was correlated with their effect on liver nucleic acid metabolism. Feeding of 4-nitrostilbene caused a selective inhibition of Mn2+-(NH4)2SO4-activated RNA polymerase activity of liver nuclei and reduced liver RNA content. The deleterious alteration of liver RNA metabolism was followed by the enhancement in the incorporation of ip-injected 3H-thymidine into DNA of liver nuclei. On the other hand, feeding of diethylstilbestrol increased tissue RNA content without effect on RNA polymerase activity of liver nuclei, and had an activity of increasing the incorporation of 3H-thymidine into DNA. The possible implication of these results with regard to the enhancement and inhibition of hepatocarcinogenesis is discussed.", "contents": "Enhancing and inhibitory effects of some stilbene and steroid compounds on induction of hepatoma in rats fed 3'-methyl-4-(dimethylamino)azobenzene. Examinations were made on substances that enhance or inhibit the induction of hepatoma in rats previously fed 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) for a brief period. The substances tested were stilbene, 4-nitrostilbene, 4,4'-dihydroxystilbene, diethylstilbestrol, 17beta-estradiol, and methyltestosterone. Male Donryu rats were fed 0.5 g of 3'-Me-DAB by being maintained on a diet containing 0.06% 3'-Me-DAB, and then they were fed 0.25 or 0.5 g of a test substance with the basal diet. Comparison of the development and yield of hepatomas indicated that 4-nitrostilbene and methyltestosterone had an activity of enhancing 3'-Me-DAB carcinogenesis, whereas diethylstilbestrol and 17beta-estradiol had an activity to retard it. Other substances showed no such activities. The enhancement by 4-nitrostilbene and inhibition by diethylstilbestrol of 3'-Me-DAB carcinogenesis was correlated with their effect on liver nucleic acid metabolism. Feeding of 4-nitrostilbene caused a selective inhibition of Mn2+-(NH4)2SO4-activated RNA polymerase activity of liver nuclei and reduced liver RNA content. The deleterious alteration of liver RNA metabolism was followed by the enhancement in the incorporation of ip-injected 3H-thymidine into DNA of liver nuclei. On the other hand, feeding of diethylstilbestrol increased tissue RNA content without effect on RNA polymerase activity of liver nuclei, and had an activity of increasing the incorporation of 3H-thymidine into DNA. The possible implication of these results with regard to the enhancement and inhibition of hepatocarcinogenesis is discussed."}
{"id": "PMID:208907", "title": "Transformation of Indian muntjac cells by murine and avian sarcoma viruses.", "content": "Indian muntjac cells were efficiently transformed by murine sarcoma virus (MSV) and avian sarcoma viruses (ASV). When colony formation of the infected cells was examined in soft agar, many colonies were formed by the ASV-injected cells but no colony was seen in the MSV-infected cells. The ASV-transformed cell clones differed among the clones in morphology, presence of inducible ASV genome, and karyotypes.", "contents": "Transformation of Indian muntjac cells by murine and avian sarcoma viruses. Indian muntjac cells were efficiently transformed by murine sarcoma virus (MSV) and avian sarcoma viruses (ASV). When colony formation of the infected cells was examined in soft agar, many colonies were formed by the ASV-injected cells but no colony was seen in the MSV-infected cells. The ASV-transformed cell clones differed among the clones in morphology, presence of inducible ASV genome, and karyotypes."}
{"id": "PMID:208910", "title": "Granular cell tumors of the esophagus.", "content": "Three cases of granular cell tumor of the esophagus are added to the 17 previously reported in the literature. These tumors, thought to be of neural origin, are difficult to diagnose preoperatively. The diagnosis should be considered in adult females presenting with an intramural mass of the proximal or distal third of the esophagus. Symptoms of dysphagia and substernal discomfort are likely to occur with lesions greater than one centimeter in diameter. Preoperative biopsy is not advised as a mistaken diagnosis of squamous cell carcinoma can result.", "contents": "Granular cell tumors of the esophagus. Three cases of granular cell tumor of the esophagus are added to the 17 previously reported in the literature. These tumors, thought to be of neural origin, are difficult to diagnose preoperatively. The diagnosis should be considered in adult females presenting with an intramural mass of the proximal or distal third of the esophagus. Symptoms of dysphagia and substernal discomfort are likely to occur with lesions greater than one centimeter in diameter. Preoperative biopsy is not advised as a mistaken diagnosis of squamous cell carcinoma can result."}
{"id": "PMID:208911", "title": "Calcified primary tumors of the gastrointestinal tract.", "content": "The dominant pattern and location of calcifications occurring within 23 primary gastrointestinal tumors have been analysed and correlated with the data from the literature. The provided guidelines for radiologic diagnosis of such calcified tumors include: (1) a retrocardiac mass containing amorphous calcifications is typical of leiomyoma of the esophagus; (2) calcific deposits similar to that in uterine fibroids may be the feature of gastric leiomyoma or intestinal leiomyosarcoma; (3) sand-like deposits within the wall of the stomach or colon are characteristic of a mucinous adenocarcinoma; (4) clusters of phleboliths in the gastrointestinal wall suggest a hemangioma particularly if recurrent intestinal bleeding and cutaneous hemangiomas are associated; (5) sunburst type of calcification in the pancreas indicates a cystadenoma or cystadenocarcinoma of that organ; and (6) aggregates of granular calcifications in the liver are diagnostic for metastatic adenocarcinoma of the colon but may rarely be seen in a primary malignancy of the liver.", "contents": "Calcified primary tumors of the gastrointestinal tract. The dominant pattern and location of calcifications occurring within 23 primary gastrointestinal tumors have been analysed and correlated with the data from the literature. The provided guidelines for radiologic diagnosis of such calcified tumors include: (1) a retrocardiac mass containing amorphous calcifications is typical of leiomyoma of the esophagus; (2) calcific deposits similar to that in uterine fibroids may be the feature of gastric leiomyoma or intestinal leiomyosarcoma; (3) sand-like deposits within the wall of the stomach or colon are characteristic of a mucinous adenocarcinoma; (4) clusters of phleboliths in the gastrointestinal wall suggest a hemangioma particularly if recurrent intestinal bleeding and cutaneous hemangiomas are associated; (5) sunburst type of calcification in the pancreas indicates a cystadenoma or cystadenocarcinoma of that organ; and (6) aggregates of granular calcifications in the liver are diagnostic for metastatic adenocarcinoma of the colon but may rarely be seen in a primary malignancy of the liver."}
{"id": "PMID:208912", "title": "Duodeno-duodenal fistula--a manifestation of carcinoma of the colon.", "content": "Two cases of duodeno-duodenal fistula complicating carcinoma of the right colon, both presenting with upper gastrointestinal hemorrhage, are presented. The close proximity of the ascending colon and hepatic flexure and their draining lymphatics to the duodenum are discussed.", "contents": "Duodeno-duodenal fistula--a manifestation of carcinoma of the colon. Two cases of duodeno-duodenal fistula complicating carcinoma of the right colon, both presenting with upper gastrointestinal hemorrhage, are presented. The close proximity of the ascending colon and hepatic flexure and their draining lymphatics to the duodenum are discussed."}
{"id": "PMID:208913", "title": "A case of rectal carcinoma concomitant with Pagetoid lesion in the perianal region--histopathological and electron microscopic observations--.", "content": "A case of extramammary Paget's disease of the perianal area adjacent to a mucinous adenocarcinoma of the rectum is presented. The histopathological examination of the case revealed that within the epidermis adjacent to the invading rectal cancer nest, the formation of glandular structures can be observed occasionally, around which so-called Paget's cells are noted to be scattered and further many points of similarity between cancer cell and Paget's cell are proved by electron microscope. Perianal skin lesion looking like Paget's disease is proved to be due to intraepidermal spread of the rectal carcinoma. Referring to the literature, this is the first report to our knowledge, to elucidate the histogenesis of perianal extramammary Paget's disease associated with a rectal carcinoma using the electron microscopy.", "contents": "A case of rectal carcinoma concomitant with Pagetoid lesion in the perianal region--histopathological and electron microscopic observations--. A case of extramammary Paget's disease of the perianal area adjacent to a mucinous adenocarcinoma of the rectum is presented. The histopathological examination of the case revealed that within the epidermis adjacent to the invading rectal cancer nest, the formation of glandular structures can be observed occasionally, around which so-called Paget's cells are noted to be scattered and further many points of similarity between cancer cell and Paget's cell are proved by electron microscope. Perianal skin lesion looking like Paget's disease is proved to be due to intraepidermal spread of the rectal carcinoma. Referring to the literature, this is the first report to our knowledge, to elucidate the histogenesis of perianal extramammary Paget's disease associated with a rectal carcinoma using the electron microscopy."}
{"id": "PMID:208914", "title": "Lipoprotein-X levels in extrahepatic versus intrahepatic cholestasis.", "content": "Lipoprotein-X (LP-X) is an abnormal lipoprotein characteristic of cholestasis. To assess recent claims that its serum concentration helps differentiate extrahepatic from intrahepatic cholestasis, we studied 42 consecutive LP-X-positive patients. The mean serum LP-X level was higher in 18 patients with extrahepatic obstruction than in 24 with intrahepatic cholestatis, 321 +/- 89 versus 130 +/- 31 SEM mg per dl (P less than 0.05). However, values overlapped in 38 of the 42 cases, and in the other 4 the diagnosis of extrahepatic obstruction was obvious anyway from clinical examination. LP-X concentration gave little more information than did free cholesterol of phospholipid levels, which it closely paralleled (r = 0.89 and 0.81, respectively, P less than 0.01). There was no correlation with standard liver function tests or with activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. Contrary to recent claims, these findings suggest that serum LP-X quantitation has little or no clinical value in distinguishing extrahepatic from intrahepatic cholestasis.", "contents": "Lipoprotein-X levels in extrahepatic versus intrahepatic cholestasis. Lipoprotein-X (LP-X) is an abnormal lipoprotein characteristic of cholestasis. To assess recent claims that its serum concentration helps differentiate extrahepatic from intrahepatic cholestasis, we studied 42 consecutive LP-X-positive patients. The mean serum LP-X level was higher in 18 patients with extrahepatic obstruction than in 24 with intrahepatic cholestatis, 321 +/- 89 versus 130 +/- 31 SEM mg per dl (P less than 0.05). However, values overlapped in 38 of the 42 cases, and in the other 4 the diagnosis of extrahepatic obstruction was obvious anyway from clinical examination. LP-X concentration gave little more information than did free cholesterol of phospholipid levels, which it closely paralleled (r = 0.89 and 0.81, respectively, P less than 0.01). There was no correlation with standard liver function tests or with activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. Contrary to recent claims, these findings suggest that serum LP-X quantitation has little or no clinical value in distinguishing extrahepatic from intrahepatic cholestasis."}
{"id": "PMID:208917", "title": "[Diagnosis of tumor or metastasis in the liver by means of laparoscopy and gammagraphy].", "content": "Fifty-four patients with proven malignancy of the gastrointestinal tract or suspicion of primary or metastatic hepatic carcinoma were studied to evaluate the effectiveness of different diagnostic methods. Gammagraphic and laparoscopic evaluations were emphasized. The results indicated that laparoscopy was the most effective method for diagnosing primary or metastatic neoplastic liver disease.", "contents": "[Diagnosis of tumor or metastasis in the liver by means of laparoscopy and gammagraphy]. Fifty-four patients with proven malignancy of the gastrointestinal tract or suspicion of primary or metastatic hepatic carcinoma were studied to evaluate the effectiveness of different diagnostic methods. Gammagraphic and laparoscopic evaluations were emphasized. The results indicated that laparoscopy was the most effective method for diagnosing primary or metastatic neoplastic liver disease."}
{"id": "PMID:208918", "title": "Stimulation by gastro-intestinal hormones of cyclic adenosine 3': 5'-monophosphate accumulation and insulin release in isolated pancreatic islets of the rat.", "content": "In collagenase isolated rat pancreatic islets, CCK-PZ, SHG, secretin and glucagon stimulated the accumulation of cAMP, in physiological ranges. The resulting increment of cAMP showed a good correlation with insulin release stimulated by either glucagon or secretin, but not by SHG or CCK-PZ. In the same system, 14CO2 production from glucose-U-14C was significantly increased by either SHG or CCK-PZ. The results presented in this report are compatible with the hypothesis that insulin release by gastrointestinal hormones may be mediated by cAMP in the B-cell in the case of either glucagon or secretin; whereas, in the case of either SHG or CCK-PZ, it may presumably be mediated by an unknown mechanism in glucose metabolism, other than c-AMP.", "contents": "Stimulation by gastro-intestinal hormones of cyclic adenosine 3': 5'-monophosphate accumulation and insulin release in isolated pancreatic islets of the rat. In collagenase isolated rat pancreatic islets, CCK-PZ, SHG, secretin and glucagon stimulated the accumulation of cAMP, in physiological ranges. The resulting increment of cAMP showed a good correlation with insulin release stimulated by either glucagon or secretin, but not by SHG or CCK-PZ. In the same system, 14CO2 production from glucose-U-14C was significantly increased by either SHG or CCK-PZ. The results presented in this report are compatible with the hypothesis that insulin release by gastrointestinal hormones may be mediated by cAMP in the B-cell in the case of either glucagon or secretin; whereas, in the case of either SHG or CCK-PZ, it may presumably be mediated by an unknown mechanism in glucose metabolism, other than c-AMP."}
{"id": "PMID:208919", "title": "[Angiographic aspects of tumors of the islet of the pancreas].", "content": "Four patients with islet cell tumours were explored with selective angiography. The radiological findings of 3 insulinomas and 1 nonfunctioning tumor are described. The typical hypervascular pattern of parenchimatose phase was found in all. The three insulinomas were successfully treated surgically. The nonfunctioning tumor was not removed due to the pathologists original impression that it was a maligant tumor involving the portal vein. Angiographic pattern, etiology, differential diagnosis and causes of errors are discussed. The method is diagnostically useful and offers important precperative information thus reducing operating time and minimizing the magnitude of the surgery.", "contents": "[Angiographic aspects of tumors of the islet of the pancreas]. Four patients with islet cell tumours were explored with selective angiography. The radiological findings of 3 insulinomas and 1 nonfunctioning tumor are described. The typical hypervascular pattern of parenchimatose phase was found in all. The three insulinomas were successfully treated surgically. The nonfunctioning tumor was not removed due to the pathologists original impression that it was a maligant tumor involving the portal vein. Angiographic pattern, etiology, differential diagnosis and causes of errors are discussed. The method is diagnostically useful and offers important precperative information thus reducing operating time and minimizing the magnitude of the surgery."}
{"id": "PMID:208930", "title": "Canine kidney cells: I. Neutral lipids, phospholipids and fatty acids of SV40 transformed canine kidney cells in suspension and monolayer culture.", "content": "Differences in lipid composition and the effects of monolayer and suspension culture on SV40 virus transformed canine kidney cells and their plasma membranes were studied. Plasma membranes from monolayer and suspension cultures of SV40 transformed canine kidney cells were isolated by the Warren fluorescein-mercuric acetate technique. Free cholesterol was the major neutral lipid extracted from the whole cells and plasma membranes of all these cultures. Triglyceride increased about 6- to 50-fold in suspension grown whole cells and their plasma membranes compared to those from monolayer cultures. The mu moles of total neutral lipids and phospholipids are elevated in plasma membranes compared to whole cells from monolayer cultures but are similar in suspension cultures. The distribution of fatty acids in the major lipid classes of plasma membranes and whole cells generally follow the composition of calf serum used in the culture media. INDEX WORDS: SV40, plasma membranes, transformed cells, canine kidney cells, neutral lipids, phospholipids, monolayer culture, suspension culture.", "contents": "Canine kidney cells: I. Neutral lipids, phospholipids and fatty acids of SV40 transformed canine kidney cells in suspension and monolayer culture. Differences in lipid composition and the effects of monolayer and suspension culture on SV40 virus transformed canine kidney cells and their plasma membranes were studied. Plasma membranes from monolayer and suspension cultures of SV40 transformed canine kidney cells were isolated by the Warren fluorescein-mercuric acetate technique. Free cholesterol was the major neutral lipid extracted from the whole cells and plasma membranes of all these cultures. Triglyceride increased about 6- to 50-fold in suspension grown whole cells and their plasma membranes compared to those from monolayer cultures. The mu moles of total neutral lipids and phospholipids are elevated in plasma membranes compared to whole cells from monolayer cultures but are similar in suspension cultures. The distribution of fatty acids in the major lipid classes of plasma membranes and whole cells generally follow the composition of calf serum used in the culture media. INDEX WORDS: SV40, plasma membranes, transformed cells, canine kidney cells, neutral lipids, phospholipids, monolayer culture, suspension culture."}
{"id": "PMID:208933", "title": "[Effects of selective applications of drugs affecting ganglionic transmission to the hypogastric ganglion of the guinea pig (author's transl)].", "content": "Effects of selective applications of drugs to the guinea pig hypogastric ganglion were studied on the contractile response of the vas deferens to the hypogastric nerve stimulation or to ganglionic stimulating drugs. Both acetylcholine (ACh) and dimethylphenylpiperazinium (DMPP) contracted the vas deferens. Neostigmine  potentiated the ACh-induced contractions but not those which were DMPP-induced. Hemicholinium-3 (HC-3) reduced the response to nerve stimulation (R-NS) but affected neither the ACh-induced contractions nor the DMPP-induced contractions. Morphine blocked R-NS but not the ACh-induced and the DMPP-induced contractions. Hexamethonium reduced R-NS and the contractions to ACh or to DMPP. Methacholine and bethanechol applied before and after preganglionic tetanic stimulation of the hypogastric nerve produced no change of tone of the vas deferens. Atropine did not antagonize the responses which were produced by nerve stimulation, ACh or DMPP. These results support the classic hypothesis that ganglionic transmission is mediated by nicotinic receptors but do not provide evidence that muscarinic receptors exist at the synapses of this preparation.", "contents": "[Effects of selective applications of drugs affecting ganglionic transmission to the hypogastric ganglion of the guinea pig (author's transl)]. Effects of selective applications of drugs to the guinea pig hypogastric ganglion were studied on the contractile response of the vas deferens to the hypogastric nerve stimulation or to ganglionic stimulating drugs. Both acetylcholine (ACh) and dimethylphenylpiperazinium (DMPP) contracted the vas deferens. Neostigmine  potentiated the ACh-induced contractions but not those which were DMPP-induced. Hemicholinium-3 (HC-3) reduced the response to nerve stimulation (R-NS) but affected neither the ACh-induced contractions nor the DMPP-induced contractions. Morphine blocked R-NS but not the ACh-induced and the DMPP-induced contractions. Hexamethonium reduced R-NS and the contractions to ACh or to DMPP. Methacholine and bethanechol applied before and after preganglionic tetanic stimulation of the hypogastric nerve produced no change of tone of the vas deferens. Atropine did not antagonize the responses which were produced by nerve stimulation, ACh or DMPP. These results support the classic hypothesis that ganglionic transmission is mediated by nicotinic receptors but do not provide evidence that muscarinic receptors exist at the synapses of this preparation."}
{"id": "PMID:208936", "title": "[The medical after care of patients with stomas].", "content": "The medical care of the increasing number of ostomy patients is necessary in three inseparable areas:--provision of the stoma,--treatment of basis disease,--psychological support. The major medical and technical advances of recent years allow a normal social life. A precisely defined program of examinations at regular intervals is necessary to ensure adequate treatment; especially after Ca-operations. Psychological support must be directed towards the prevention of social isolation. In order to improve the present situation in the German Federal Republic the graduate training of the doctors must be intensified. In order to deal with problematical cases special ostomy out-patient clinics with suitably trained personnel should be set up in certain hospitals.", "contents": "[The medical after care of patients with stomas]. The medical care of the increasing number of ostomy patients is necessary in three inseparable areas:--provision of the stoma,--treatment of basis disease,--psychological support. The major medical and technical advances of recent years allow a normal social life. A precisely defined program of examinations at regular intervals is necessary to ensure adequate treatment; especially after Ca-operations. Psychological support must be directed towards the prevention of social isolation. In order to improve the present situation in the German Federal Republic the graduate training of the doctors must be intensified. In order to deal with problematical cases special ostomy out-patient clinics with suitably trained personnel should be set up in certain hospitals."}
{"id": "PMID:208939", "title": "Glycogen metabolism in the placenta of streptozotocin diabetic rats.", "content": "Administration of STZ prior to mating, induced significant impairment in glycogen metabolism in term rat placentae. Glycogen retention was observed in the treated placentae, while glycogen synthetase activity was reduced. The glycogenolytic pathway seemed to proceed mainly through amyloglucosidase enzyme whose activity increased threefold. Glucose-6-phosphatase showed a moderate activation, mainly in the labyrinth zone, while phosphorylase was slightly inhibited. These changes were accompanied by a decrease in placental insulin levels. The possible defensive role played by the placenta in cases of maternal hyperglycemia was postulated.", "contents": "Glycogen metabolism in the placenta of streptozotocin diabetic rats. Administration of STZ prior to mating, induced significant impairment in glycogen metabolism in term rat placentae. Glycogen retention was observed in the treated placentae, while glycogen synthetase activity was reduced. The glycogenolytic pathway seemed to proceed mainly through amyloglucosidase enzyme whose activity increased threefold. Glucose-6-phosphatase showed a moderate activation, mainly in the labyrinth zone, while phosphorylase was slightly inhibited. These changes were accompanied by a decrease in placental insulin levels. The possible defensive role played by the placenta in cases of maternal hyperglycemia was postulated."}
{"id": "PMID:208940", "title": "Effect of epinephrine and insulin on adenosine 3'5'-cyclic monophosphate--dependent protein kinase in human skeletal muscle in vivo.", "content": "Cyclic AMP dependent protein kinase has beeen identified in human skeletal muscle tissue. In crude muscle extracts the enzyme was 3--5 fold activated by cyclic AMP. The cyclic AMP-dependent activity (corresponding to the inactive holoenzyme) was completely inhibited by the heat stable inhibitor of protein kinase. Reciprocal changes of the cyclic AMP-dependent activity in skeletal muscle were observed after administration of epinephrine and insulin in vivo. Infusion of epinephrine in healthy volunteers increased the level of cyclic AMP and decreased the activity of the cyclic AMP-depenent form (i.e. the inactive form) of protein kinase. These changes were reversible after cessation of epinephrine administration. The results are consistent with an activation of protein kinase in vivo due to an epinephrine mediated increase of the concentration of cyclic AMP. I.v. injection of insulin had the opposite effect on the enzyme in skeletal muscle, leading to increased activity of the cyclic AMP-dependent form of protein kinase. Insulin had no effect on the level of cyclic AMP, but promoted a transient increase of cyclic GMP 1 min. after insulin injection. The effect by insulin on protein kinase cannot be related to the level of cyclic AMP or cyclic GMP.", "contents": "Effect of epinephrine and insulin on adenosine 3'5'-cyclic monophosphate--dependent protein kinase in human skeletal muscle in vivo. Cyclic AMP dependent protein kinase has beeen identified in human skeletal muscle tissue. In crude muscle extracts the enzyme was 3--5 fold activated by cyclic AMP. The cyclic AMP-dependent activity (corresponding to the inactive holoenzyme) was completely inhibited by the heat stable inhibitor of protein kinase. Reciprocal changes of the cyclic AMP-dependent activity in skeletal muscle were observed after administration of epinephrine and insulin in vivo. Infusion of epinephrine in healthy volunteers increased the level of cyclic AMP and decreased the activity of the cyclic AMP-depenent form (i.e. the inactive form) of protein kinase. These changes were reversible after cessation of epinephrine administration. The results are consistent with an activation of protein kinase in vivo due to an epinephrine mediated increase of the concentration of cyclic AMP. I.v. injection of insulin had the opposite effect on the enzyme in skeletal muscle, leading to increased activity of the cyclic AMP-dependent form of protein kinase. Insulin had no effect on the level of cyclic AMP, but promoted a transient increase of cyclic GMP 1 min. after insulin injection. The effect by insulin on protein kinase cannot be related to the level of cyclic AMP or cyclic GMP."}
{"id": "PMID:208941", "title": "Effect of acute ethanol load on plasma immunoreactive insulin and glucagon.", "content": "The effect of a single large dose of ethanol (5 mg/kg body weight) on plasma glucagon (IRG) and insulin (IRI) concentrations was studied in rats fasting for 24 hr. Hepatic cAMP concentration and blood glucose were also estimated and correlated with hormonal changes. Plasma IRG concentrations had doubled by the first sampling time (2 hr) and remained at this level up to 16 hr after ethanol administration. Plasma IRI concentrations were not affected by ethanol. Hepatic cAMP concentrations reflected changes in the plasma insulin/glucagon ratio, which seems to be the major determining factor for hepatic cAMP even during ethanol oxidation. Hypoglycemia was not found in the ethanol group during the experimental period of 24 hr, and it was therefore concluded that ethanol may stimulate glucagon secretion in rats even without concurrent hypoglycemia. Possible mechanisms for the action of ethanol on the endocrine pancrease are discussed.", "contents": "Effect of acute ethanol load on plasma immunoreactive insulin and glucagon. The effect of a single large dose of ethanol (5 mg/kg body weight) on plasma glucagon (IRG) and insulin (IRI) concentrations was studied in rats fasting for 24 hr. Hepatic cAMP concentration and blood glucose were also estimated and correlated with hormonal changes. Plasma IRG concentrations had doubled by the first sampling time (2 hr) and remained at this level up to 16 hr after ethanol administration. Plasma IRI concentrations were not affected by ethanol. Hepatic cAMP concentrations reflected changes in the plasma insulin/glucagon ratio, which seems to be the major determining factor for hepatic cAMP even during ethanol oxidation. Hypoglycemia was not found in the ethanol group during the experimental period of 24 hr, and it was therefore concluded that ethanol may stimulate glucagon secretion in rats even without concurrent hypoglycemia. Possible mechanisms for the action of ethanol on the endocrine pancrease are discussed."}
{"id": "PMID:208942", "title": "Influence of genetic obesity in mice on the lipolytic response of isolated adipocytes to isoproterenol and ACTH-(1-24).", "content": "The lipolytic response of isolated adipocytes from genetic obese (C57/BL/64 ob/ob) and lean (C57BL/6J +/?) mice to ACTH-(1-24), isoproterenol and glucagon has been studied. The mean cell idameter of adipocytes form ob/ob mice was approximately twice that of lean controls. The adipocytes from obese mice contained on the average approximately six times the amount of triacylglycerol present in the smaller lean mouse adipocyte. Lipolysis was calculated both on a per cell basis (10(5) cells) and per mu mole of triacylglycerol and when expressed on a cell number basis, the larger adipocytes from obese mice showed an ACTH-(1-24) stimulated glycerol release which was quantitatively similar to that of smaller adipocytes from lean mice. When expressed per mu mole of triacylglycerol, the smaller cells from lean animals appeared to be dramatically more responsive to either isoproterenol or ACTH-(1-24). On either basis, ACTH-(1-24) stimulated glycerol release from obese mouse cells was greater than the isoproterenol response. The obese mouse of adipocyte showed selective loss of response to isoproterenol compared to its lean control.", "contents": "Influence of genetic obesity in mice on the lipolytic response of isolated adipocytes to isoproterenol and ACTH-(1-24). The lipolytic response of isolated adipocytes from genetic obese (C57/BL/64 ob/ob) and lean (C57BL/6J +/?) mice to ACTH-(1-24), isoproterenol and glucagon has been studied. The mean cell idameter of adipocytes form ob/ob mice was approximately twice that of lean controls. The adipocytes from obese mice contained on the average approximately six times the amount of triacylglycerol present in the smaller lean mouse adipocyte. Lipolysis was calculated both on a per cell basis (10(5) cells) and per mu mole of triacylglycerol and when expressed on a cell number basis, the larger adipocytes from obese mice showed an ACTH-(1-24) stimulated glycerol release which was quantitatively similar to that of smaller adipocytes from lean mice. When expressed per mu mole of triacylglycerol, the smaller cells from lean animals appeared to be dramatically more responsive to either isoproterenol or ACTH-(1-24). On either basis, ACTH-(1-24) stimulated glycerol release from obese mouse cells was greater than the isoproterenol response. The obese mouse of adipocyte showed selective loss of response to isoproterenol compared to its lean control."}
{"id": "PMID:208943", "title": "An increase of pituitary 3', 5' cyclic adenosine monophosphate produced by estradiol benzoate in vitro: possible implication of this increase in the secretion of luteinizing hormone.", "content": "In an attempt to study the site and mechanism of action of estrogen in producing positive feedback control, porcine anterior pituitary slices were incubated in vitro in the presence of estradiol benzoate (EB). EB elevated pituitary cyclic AMP concentration within 5 min and augmented pituitary release of luteinizing hormone (LH). The magnitude of increase of cyclic AMP and LH release was related to the doses of EB used. Also, luteinizing hormone releasing hormone (LH-RH) elevated pituitary cyclic AMP concentration and stimulated pituitary release of LH. The magnitude of increase of cyclic AMP and LH release was inversely related to the doses of LH-RH used. EB and LH-RH were additive in increasing cyclic AMP. Progesterone and clomiphene citrate interfered with an increase of pituitary cyclic AMP produced by EB, but did not significantly affect the basal level of pituitary cyclic AMP. Testosterone propionate, human chorionic gonadotropin and hexestrol were without effect on either basal or stimulated level of pituitary cyclic AMP. Since cyclic AMP and dibutyryl cyclic AMP (DBC) stimulated LH release, it is suggested that EB directly stimulates the release of LH by augmenting cyclic AMP synthesis in the anterior pituitary.", "contents": "An increase of pituitary 3', 5' cyclic adenosine monophosphate produced by estradiol benzoate in vitro: possible implication of this increase in the secretion of luteinizing hormone. In an attempt to study the site and mechanism of action of estrogen in producing positive feedback control, porcine anterior pituitary slices were incubated in vitro in the presence of estradiol benzoate (EB). EB elevated pituitary cyclic AMP concentration within 5 min and augmented pituitary release of luteinizing hormone (LH). The magnitude of increase of cyclic AMP and LH release was related to the doses of EB used. Also, luteinizing hormone releasing hormone (LH-RH) elevated pituitary cyclic AMP concentration and stimulated pituitary release of LH. The magnitude of increase of cyclic AMP and LH release was inversely related to the doses of LH-RH used. EB and LH-RH were additive in increasing cyclic AMP. Progesterone and clomiphene citrate interfered with an increase of pituitary cyclic AMP produced by EB, but did not significantly affect the basal level of pituitary cyclic AMP. Testosterone propionate, human chorionic gonadotropin and hexestrol were without effect on either basal or stimulated level of pituitary cyclic AMP. Since cyclic AMP and dibutyryl cyclic AMP (DBC) stimulated LH release, it is suggested that EB directly stimulates the release of LH by augmenting cyclic AMP synthesis in the anterior pituitary."}
{"id": "PMID:208944", "title": "The effect of cyclic nucleotides on the incorporation of 3H-glucosamine into hyaluronate in bone organ culture.", "content": "Addition of dibutyryl cyclic AMP or parathyroid hormone to bone organ cultures markedly increased the incorporation of 3H-glucosamine into non-dialyzable macromolecules. Other cyclic nucleotides or their dibutyryl derivatives did not stimulate glucosamine incorporation. DEAE-cellulose chromatography of the papain-digested calvaria and culture medium resolved the labeled material into four peaks. A four-fold increase in radioactivity was observed in peak III. Previous studies of peak III have identified the labeled material as hyaluronic acid. The results suggest that the parathyroid hormone stimulated increase in glucosamine incorporation is mediated via the adenylate cyclase-cyclic AMP system, and that the increased amount of radioactivity is due to an increased amount of hyaluronic acid. Turnover studied of the labeled material suggest that the release of proteoglycans into the culture medium is not inhibited in the cultures treated with dibutyryl cyclic AMP. The role of hyaluronate in this experimental system remains to be elucidated.", "contents": "The effect of cyclic nucleotides on the incorporation of 3H-glucosamine into hyaluronate in bone organ culture. Addition of dibutyryl cyclic AMP or parathyroid hormone to bone organ cultures markedly increased the incorporation of 3H-glucosamine into non-dialyzable macromolecules. Other cyclic nucleotides or their dibutyryl derivatives did not stimulate glucosamine incorporation. DEAE-cellulose chromatography of the papain-digested calvaria and culture medium resolved the labeled material into four peaks. A four-fold increase in radioactivity was observed in peak III. Previous studies of peak III have identified the labeled material as hyaluronic acid. The results suggest that the parathyroid hormone stimulated increase in glucosamine incorporation is mediated via the adenylate cyclase-cyclic AMP system, and that the increased amount of radioactivity is due to an increased amount of hyaluronic acid. Turnover studied of the labeled material suggest that the release of proteoglycans into the culture medium is not inhibited in the cultures treated with dibutyryl cyclic AMP. The role of hyaluronate in this experimental system remains to be elucidated."}
{"id": "PMID:208945", "title": "Changes in the microheterogeneity of histone H1 after mengovirus infection of Ehrlich ascites tumor cells.", "content": "Employing high-resolution polyacryl-amide gradient slab-gel electrophoresis in 6M urea and 6% acetic acid, a distinct change in the microheterogeneity of histone H1 was detected after mengovirus infection of Ehrlich ascites tumor cells. Whereas in uninfected cells the band multiplicity was found to be 6, it was reduced to 4 in the course of the infectious cycle (8 to 9 h). It could be deomonstrated that, while the electrophoretically slowly moving subspecies H1e and H1f disappeared from the band profile of histone H1, the faster migrating bands H1a and H1b increased in relative intensity. The relative intensity of band H1d was also drastically reduced, that of band H1c stayed practically constant throughout infection. When Ehrlich ascites tumor cells were labeled with a mixture of [14C]amino acids prior to mengovirus infection, the radioactivity incorporated into histone H1 subspecies of low electrophoretic mobility was chased into histone H1 components of high mobility in the course of infection, suggesting a virus-induced, unidirectional interconversion of the multiple histone H1 subunits. With the exception of a histone H2B subspecies, which also decreased in amount, the relative quantities of the other histones stayed constant throughout infection.", "contents": "Changes in the microheterogeneity of histone H1 after mengovirus infection of Ehrlich ascites tumor cells. Employing high-resolution polyacryl-amide gradient slab-gel electrophoresis in 6M urea and 6% acetic acid, a distinct change in the microheterogeneity of histone H1 was detected after mengovirus infection of Ehrlich ascites tumor cells. Whereas in uninfected cells the band multiplicity was found to be 6, it was reduced to 4 in the course of the infectious cycle (8 to 9 h). It could be deomonstrated that, while the electrophoretically slowly moving subspecies H1e and H1f disappeared from the band profile of histone H1, the faster migrating bands H1a and H1b increased in relative intensity. The relative intensity of band H1d was also drastically reduced, that of band H1c stayed practically constant throughout infection. When Ehrlich ascites tumor cells were labeled with a mixture of [14C]amino acids prior to mengovirus infection, the radioactivity incorporated into histone H1 subspecies of low electrophoretic mobility was chased into histone H1 components of high mobility in the course of infection, suggesting a virus-induced, unidirectional interconversion of the multiple histone H1 subunits. With the exception of a histone H2B subspecies, which also decreased in amount, the relative quantities of the other histones stayed constant throughout infection."}
{"id": "PMID:208946", "title": "Enhanced phosphorylation of ribosomal protein s6 and other cytoplasmic proteins after mengovirus infection of Ehrlich ascites tumor cells.", "content": "After mengovirus infection of Ehrlich ascites tumor cells, an increased incorporation of radioactive phosphate into ribosomal protein S6 was detected. As judged from the shape of the radioautography spot and the location of the modified protein on the two-dimensional polyacrylamide gel, it must be concluded that more than one phosphate group was incorporated into ribosomal protein S6. Concomitantly, multiple cytoplasmic proteins, particularly those with high affinity for ribosomes, were phosphorylated. Compared with the controls (mock infection), mengovirus infection induced only a slight additional phosphorylation of the proteins of the ribosome-free supernatant. Employing the radio isotope dilution test with 3', 5'-cyclic AMP-binding protein, no enhancement of the intracellular concentration of 3', 5'-cyclic AMP in response to mengovirus infection could be deomonstrated.", "contents": "Enhanced phosphorylation of ribosomal protein s6 and other cytoplasmic proteins after mengovirus infection of Ehrlich ascites tumor cells. After mengovirus infection of Ehrlich ascites tumor cells, an increased incorporation of radioactive phosphate into ribosomal protein S6 was detected. As judged from the shape of the radioautography spot and the location of the modified protein on the two-dimensional polyacrylamide gel, it must be concluded that more than one phosphate group was incorporated into ribosomal protein S6. Concomitantly, multiple cytoplasmic proteins, particularly those with high affinity for ribosomes, were phosphorylated. Compared with the controls (mock infection), mengovirus infection induced only a slight additional phosphorylation of the proteins of the ribosome-free supernatant. Employing the radio isotope dilution test with 3', 5'-cyclic AMP-binding protein, no enhancement of the intracellular concentration of 3', 5'-cyclic AMP in response to mengovirus infection could be deomonstrated."}
{"id": "PMID:208947", "title": "Multiple protein kinases from Trypanosoma gambiense.", "content": "Three protein kinases were distinguished in Trypanosoma gambiense extract. The enzymes preferred phosvitin, histone, and protamine as acceptor proteins, respectively. The amino acid residues of the acceptor proteins which were phosphorylated by these protein-kinase activities were serine and- to less extent- threonine. The protein kinase activities were neither affected by cyclic nucleotides nor by cyclic AMP receptors. The molecular weights of these protein kinases were determined to be greater than 200,000, 95000 and 37000, respectively. The activities of all three protein kinases were affected to varying degrees by nucleotides and nucleosides.", "contents": "Multiple protein kinases from Trypanosoma gambiense. Three protein kinases were distinguished in Trypanosoma gambiense extract. The enzymes preferred phosvitin, histone, and protamine as acceptor proteins, respectively. The amino acid residues of the acceptor proteins which were phosphorylated by these protein-kinase activities were serine and- to less extent- threonine. The protein kinase activities were neither affected by cyclic nucleotides nor by cyclic AMP receptors. The molecular weights of these protein kinases were determined to be greater than 200,000, 95000 and 37000, respectively. The activities of all three protein kinases were affected to varying degrees by nucleotides and nucleosides."}
{"id": "PMID:208948", "title": "Adenosine 3', 5'-cyclic monophosphate-binding proteins from Trypanosoma gambiense.", "content": "Two cyclic AMP-binding proteins, not identical with regulatory subunits of protein kinases, have been isolated from Trypanosoma gambiense. The cyclic AMP receptors were separated by gel chromatography on the basis of their molecular weights. The binding constants of the high and the low molecular weight receptors for cyclic AMP were determined to be 0.4 muM and 0.6 muM, respectively. Cyclic IMP and cyclic GMP compete with cyclic AMP for the binding sites of both receptors. The cyclic AMP binding of the low molecular weight receptor was competitively inhibitied by adenine derivatives. The binding capacity of the high molecular weight receptor was enhanced about two-fold by proteolytic modification with trypsin.", "contents": "Adenosine 3', 5'-cyclic monophosphate-binding proteins from Trypanosoma gambiense. Two cyclic AMP-binding proteins, not identical with regulatory subunits of protein kinases, have been isolated from Trypanosoma gambiense. The cyclic AMP receptors were separated by gel chromatography on the basis of their molecular weights. The binding constants of the high and the low molecular weight receptors for cyclic AMP were determined to be 0.4 muM and 0.6 muM, respectively. Cyclic IMP and cyclic GMP compete with cyclic AMP for the binding sites of both receptors. The cyclic AMP binding of the low molecular weight receptor was competitively inhibitied by adenine derivatives. The binding capacity of the high molecular weight receptor was enhanced about two-fold by proteolytic modification with trypsin."}
{"id": "PMID:208949", "title": "Studies on the biosynthesis of cyclitols, XXXVI. Purification of myo-inositol-1-phosphate synthase of the duckweed, Lemna gibba, to homogeneity by affinity chromatography on NAD-Sepharose molecular and catalytic properties of the enzyme.", "content": "Using the technique of affinity chromatography on NAD-Sepharose the myo-inositol-1-phosphate synthase of Lemna gibba was purified to homogeneity. The molecular and catalytic properties of this enzyme differ very much from those of myo-inositol-1-phosphate synthase from animal sources. Thus the specific activity of the duckweed enzyme is more than two orders of magnitude higher than that of the enzyme from rat testes. It is inhibitied by EDTA and can be reactivated by Mn2. Its molecular weight (135000 +/- 5000), its subunit composition (3 subunits with identical electrophoretic behaviour) and its isoelectric point (pH 7.7) are also very different from the corresponding parameters for the animal enzyme.", "contents": "Studies on the biosynthesis of cyclitols, XXXVI. Purification of myo-inositol-1-phosphate synthase of the duckweed, Lemna gibba, to homogeneity by affinity chromatography on NAD-Sepharose molecular and catalytic properties of the enzyme. Using the technique of affinity chromatography on NAD-Sepharose the myo-inositol-1-phosphate synthase of Lemna gibba was purified to homogeneity. The molecular and catalytic properties of this enzyme differ very much from those of myo-inositol-1-phosphate synthase from animal sources. Thus the specific activity of the duckweed enzyme is more than two orders of magnitude higher than that of the enzyme from rat testes. It is inhibitied by EDTA and can be reactivated by Mn2. Its molecular weight (135000 +/- 5000), its subunit composition (3 subunits with identical electrophoretic behaviour) and its isoelectric point (pH 7.7) are also very different from the corresponding parameters for the animal enzyme."}
{"id": "PMID:208950", "title": "Carcinomas of intraoral salivary glands.", "content": "Of 44 intraoral salivary gland tumours received by the Department of Pathology, Dental Faculty, University of Oslo over the last 20 years, 21 (approx. 48%) were classified as carcinomas. Of these, the adenocarcinomas constituted the largest group, but because some of them bore a certain likeness to adenoid cystic carcinomas and to mucoepidermoid tumours, we believe that transitions exist between these groups of neoplasms. The material is thought to reflect the daily practice of oral surgeons and general dental practitioners, and we think it important to emphasize that approximately every second tumour in this series was malignant.", "contents": "Carcinomas of intraoral salivary glands. Of 44 intraoral salivary gland tumours received by the Department of Pathology, Dental Faculty, University of Oslo over the last 20 years, 21 (approx. 48%) were classified as carcinomas. Of these, the adenocarcinomas constituted the largest group, but because some of them bore a certain likeness to adenoid cystic carcinomas and to mucoepidermoid tumours, we believe that transitions exist between these groups of neoplasms. The material is thought to reflect the daily practice of oral surgeons and general dental practitioners, and we think it important to emphasize that approximately every second tumour in this series was malignant."}
{"id": "PMID:208951", "title": "Yellow-brown spindle bodies in mesenteric lymph nodes: a possible relationship with melanosis coli.", "content": "Four cases are described in which spindle-shaped, yellow-brown bodies were seen in the mesenteric lymph nodes of patients with melanosis coli. A comparison of the staining reactions and ultrastructural appearances of the spindle bodies and melanosis pigment suggest that they are related within the broad group of lipofuscins and that the spindle bodies are formed as a result of coalescence of lysosomes containing the pigment.", "contents": "Yellow-brown spindle bodies in mesenteric lymph nodes: a possible relationship with melanosis coli. Four cases are described in which spindle-shaped, yellow-brown bodies were seen in the mesenteric lymph nodes of patients with melanosis coli. A comparison of the staining reactions and ultrastructural appearances of the spindle bodies and melanosis pigment suggest that they are related within the broad group of lipofuscins and that the spindle bodies are formed as a result of coalescence of lysosomes containing the pigment."}
{"id": "PMID:208952", "title": "Carcinoma of the breast with metaplasia to chondrosarcoma: a light and electron microscopic study.", "content": "Two carcinomas of the breast containing large areas of sarcomatous tissue were studied by light and electron microscopy. In one of these, the sarcomatous element was frankly cartilaginous and in the other, predominantly myxoid but with small cartilaginous-looking foci. By light microscopy, a highly suggestive metaplastic transition could be traced from cells within the epithelial nests to those within the sarcomatous lobules. Ultrastructurally, cells in the former region showed epithelial characteristics and those in the latter region, mesenchymal and/or cartilaginous features. The carcinomatous cells contained desmosomes and formed intercellular spaces lined by microvilli; a few cells showed prominent profiles of rough endoplasmic reticulum. In the first case, the cells in the immediate vicinity of the epithelial nests and those in the fully developed cartilaginous regions showed a progressive dilatation of their endoplasmic reticulum to form large sac-like structures filled with a finely granular and floccular material. The intercellular matrix was electron lucent and contained scattered dense particles, fibrillo-granular material and collagen fibres. Condensation of this material at some distance from the cell resulted in the formation of lacunae. In the second case, the cells in the myxoid areas also showed prominent dilatation of endoplasmic reticulum.", "contents": "Carcinoma of the breast with metaplasia to chondrosarcoma: a light and electron microscopic study. Two carcinomas of the breast containing large areas of sarcomatous tissue were studied by light and electron microscopy. In one of these, the sarcomatous element was frankly cartilaginous and in the other, predominantly myxoid but with small cartilaginous-looking foci. By light microscopy, a highly suggestive metaplastic transition could be traced from cells within the epithelial nests to those within the sarcomatous lobules. Ultrastructurally, cells in the former region showed epithelial characteristics and those in the latter region, mesenchymal and/or cartilaginous features. The carcinomatous cells contained desmosomes and formed intercellular spaces lined by microvilli; a few cells showed prominent profiles of rough endoplasmic reticulum. In the first case, the cells in the immediate vicinity of the epithelial nests and those in the fully developed cartilaginous regions showed a progressive dilatation of their endoplasmic reticulum to form large sac-like structures filled with a finely granular and floccular material. The intercellular matrix was electron lucent and contained scattered dense particles, fibrillo-granular material and collagen fibres. Condensation of this material at some distance from the cell resulted in the formation of lacunae. In the second case, the cells in the myxoid areas also showed prominent dilatation of endoplasmic reticulum."}
{"id": "PMID:208953", "title": "Primary signet ring cell carcinoma of the breast.", "content": "Three examples of primary signet ring cell carcinoma of the breast are described. This form of breast carcinoma deserves recognition as an entity because its prognosis may differ from colloid carcinoma of the breast and because of potential difficulty in distinguishing it from metastatic carcinoma.", "contents": "Primary signet ring cell carcinoma of the breast. Three examples of primary signet ring cell carcinoma of the breast are described. This form of breast carcinoma deserves recognition as an entity because its prognosis may differ from colloid carcinoma of the breast and because of potential difficulty in distinguishing it from metastatic carcinoma."}
{"id": "PMID:208954", "title": "Mucin-producing carcinomas of the breast: ultrastructural observations.", "content": "The ultrastructural characteristics of mucin production in mammary mucoid carcinoma, signet ring cell carcinoma (Harris, Wells & Vasudev 1978), papillary carcinoma and lobular carcinoma are compared. The mucin in lobular carcinoma is confined to intracytoplasmic lumina whereas it is present as membrane bound granules in the other three types, although intracytoplasmic lumina also occur in the latter. A possible origin of intracytoplasmic lumina from distended Golgi cisternae is proposed. Possibly, extracellular mucin acts as a mechanical barrier between tumour cells and lymphatics, thus explaining the good prognosis of typical mucoid carcinomas.", "contents": "Mucin-producing carcinomas of the breast: ultrastructural observations. The ultrastructural characteristics of mucin production in mammary mucoid carcinoma, signet ring cell carcinoma (Harris, Wells & Vasudev 1978), papillary carcinoma and lobular carcinoma are compared. The mucin in lobular carcinoma is confined to intracytoplasmic lumina whereas it is present as membrane bound granules in the other three types, although intracytoplasmic lumina also occur in the latter. A possible origin of intracytoplasmic lumina from distended Golgi cisternae is proposed. Possibly, extracellular mucin acts as a mechanical barrier between tumour cells and lymphatics, thus explaining the good prognosis of typical mucoid carcinomas."}
{"id": "PMID:208955", "title": "Aftercare for psychiatric patients: does it prevent rehospitalization?", "content": "Focusing on a sample of 421 patients who made from one to 65 visits to an aftercare clinic, the authors replicated and extended and investigation of the effectiveness of psychiatric aftercare for patients discharged from hospital settings. A total of 167 of the patients were rehospitalized at least once during the follow-up period. The findings of both studies suggest that there is a significant relationship between an increasing number of aftercare visits and a reduced liklihood of rehospitalization, especially among the more chronic patients. The authors emphasize the need for further studies in which patients are interviewed directly about their perceptions of aftercare.", "contents": "Aftercare for psychiatric patients: does it prevent rehospitalization? Focusing on a sample of 421 patients who made from one to 65 visits to an aftercare clinic, the authors replicated and extended and investigation of the effectiveness of psychiatric aftercare for patients discharged from hospital settings. A total of 167 of the patients were rehospitalized at least once during the follow-up period. The findings of both studies suggest that there is a significant relationship between an increasing number of aftercare visits and a reduced liklihood of rehospitalization, especially among the more chronic patients. The authors emphasize the need for further studies in which patients are interviewed directly about their perceptions of aftercare."}
{"id": "PMID:208956", "title": "Congregate living for the mentally ill: patients as tenants.", "content": "The authors describe an apartment-living project for chronic mental patients released from the Hillside Division of the Long Island Jewish-Hillside Medical Center. The apartments, which are rented by the hospital and sublet to the patients, are located in modern, well-maintained high-rise buildings within commuting distance from the hospital. To avoid creating a psychiatric ghetto, the project rents no more than two apartments in buildings of a hundred or more units. The hospital was able to rent the apartments by assuring the landlords that the hospital would be a financially responsible tenant and that staff would be in continuing contact with the patients, would be available to the landlords if problems arose, and would remove troublesome tenants. Some of the problems encountered by the patients in the program are described, as are guidelines for selecting those who have a reasonable chance of benefiting from such a program.", "contents": "Congregate living for the mentally ill: patients as tenants. The authors describe an apartment-living project for chronic mental patients released from the Hillside Division of the Long Island Jewish-Hillside Medical Center. The apartments, which are rented by the hospital and sublet to the patients, are located in modern, well-maintained high-rise buildings within commuting distance from the hospital. To avoid creating a psychiatric ghetto, the project rents no more than two apartments in buildings of a hundred or more units. The hospital was able to rent the apartments by assuring the landlords that the hospital would be a financially responsible tenant and that staff would be in continuing contact with the patients, would be available to the landlords if problems arose, and would remove troublesome tenants. Some of the problems encountered by the patients in the program are described, as are guidelines for selecting those who have a reasonable chance of benefiting from such a program."}
{"id": "PMID:208957", "title": "A positive look at boarding homes.", "content": "The authors report on a project in Philadelphia in which boarding homes were successfully used to house former state hospital patients in a warm and therapeutic environment. The program was established jointly by the Jefferson Community Mental Health Center and Horizon House, a psychosocial rehabilitation agency. It drew the proprietors into the treatment program through close contact with professional staff and through meetings and seminars on various aspects of housing and care. The authors note that their positive experiences with boarding homes and their proprietors run counter to the negative experiences reported in much of the literature.", "contents": "A positive look at boarding homes. The authors report on a project in Philadelphia in which boarding homes were successfully used to house former state hospital patients in a warm and therapeutic environment. The program was established jointly by the Jefferson Community Mental Health Center and Horizon House, a psychosocial rehabilitation agency. It drew the proprietors into the treatment program through close contact with professional staff and through meetings and seminars on various aspects of housing and care. The authors note that their positive experiences with boarding homes and their proprietors run counter to the negative experiences reported in much of the literature."}
{"id": "PMID:208959", "title": "Comparative studies in two cases of testicular feminization syndrome, one with and the other without the fluorescent distal band q12 of the Y.", "content": "In two patients with testicular feminization syndrome, one Yq12-positive and the other Yq12-negative, we compared phenotype, gonadal histology and ultrastructure, in vivo steroid response of the testes to the administration of exogenous gonadotropin during adrenal suppression, and of the adrenal gland to ACTH. The assumption that the constitutive Y heterochromatin could function as a regulator of steroid biosynthesis and metabolism, with or without effect at other levels, was not firmly supported by the observations reported here. However, further studies along this line may help elucidate the biologic role of this portion of the Y chromosome in humans.", "contents": "Comparative studies in two cases of testicular feminization syndrome, one with and the other without the fluorescent distal band q12 of the Y. In two patients with testicular feminization syndrome, one Yq12-positive and the other Yq12-negative, we compared phenotype, gonadal histology and ultrastructure, in vivo steroid response of the testes to the administration of exogenous gonadotropin during adrenal suppression, and of the adrenal gland to ACTH. The assumption that the constitutive Y heterochromatin could function as a regulator of steroid biosynthesis and metabolism, with or without effect at other levels, was not firmly supported by the observations reported here. However, further studies along this line may help elucidate the biologic role of this portion of the Y chromosome in humans."}
{"id": "PMID:208960", "title": "Effect of dibutyryl cAMP on cell cycle progression of rat brain tumor cells in vitro.", "content": "Autoradiographic and flow microfluorometry analyses have been applied to a study of perturbed cell kinetics in 9L rat brain tumor cells treated with dibutyryl cyclic AMP and theophylline alone and in combination in vitro. At a concentration of 1 mM each, cell growth ceased shortly after the administration of these drugs. The results indicate that cells in S and G2 phase at the time of drug administration can undergo mitosis even though a considerable prolongation of G2 phase was apparent. However, cells in G1 at the time of drug administration was arrested in that phase, whereas those cells in S or G2 were able to complete one mitosis before becoming arrested in the G1 phase. This blocking effect was reversible, and cells resumed proliferation at a normal rate shortly after the removal of these drugs.", "contents": "Effect of dibutyryl cAMP on cell cycle progression of rat brain tumor cells in vitro. Autoradiographic and flow microfluorometry analyses have been applied to a study of perturbed cell kinetics in 9L rat brain tumor cells treated with dibutyryl cyclic AMP and theophylline alone and in combination in vitro. At a concentration of 1 mM each, cell growth ceased shortly after the administration of these drugs. The results indicate that cells in S and G2 phase at the time of drug administration can undergo mitosis even though a considerable prolongation of G2 phase was apparent. However, cells in G1 at the time of drug administration was arrested in that phase, whereas those cells in S or G2 were able to complete one mitosis before becoming arrested in the G1 phase. This blocking effect was reversible, and cells resumed proliferation at a normal rate shortly after the removal of these drugs."}
{"id": "PMID:208961", "title": "A virus-producing cell line developed by transformation of human parapharyngeal cells with SV40.", "content": "Normal cultures of epithelial appearance were initiated by trypsinization of a surgically resected, histologically normal branchial cyst. Cellular morphology was consistent with derivation from the stratified squamous epithelium of the cyst or from vascular endothelium, although electron micrographs of the cultured cells failed to show any junctional complexes. Infection with SV40 produced transformants which were also epithelioid in appearance. These grew vigorously for 22 to 50 population doublings (about 23 to 32 subcultures, depending upon regimen) and then became quiescent. During this evolution, virus was detectable at all stages by both direct isolation (cell extracts) and cocultivation with permissive cells. In two sublines in which selection for rapidly growing cell types occureed, virus was detected only by cocultivation. The work confirms that of others in the finding that normal human epithelial cells are susceptible to transformation by oncogenic viruses, but are apparently less responsive than are fibroblasts to such transforming agents. It also suggests that subcultivation techniques that maintain the populations of transformed cells at low density tend to select against cell strains that are continous producers of infectious virus.", "contents": "A virus-producing cell line developed by transformation of human parapharyngeal cells with SV40. Normal cultures of epithelial appearance were initiated by trypsinization of a surgically resected, histologically normal branchial cyst. Cellular morphology was consistent with derivation from the stratified squamous epithelium of the cyst or from vascular endothelium, although electron micrographs of the cultured cells failed to show any junctional complexes. Infection with SV40 produced transformants which were also epithelioid in appearance. These grew vigorously for 22 to 50 population doublings (about 23 to 32 subcultures, depending upon regimen) and then became quiescent. During this evolution, virus was detectable at all stages by both direct isolation (cell extracts) and cocultivation with permissive cells. In two sublines in which selection for rapidly growing cell types occureed, virus was detected only by cocultivation. The work confirms that of others in the finding that normal human epithelial cells are susceptible to transformation by oncogenic viruses, but are apparently less responsive than are fibroblasts to such transforming agents. It also suggests that subcultivation techniques that maintain the populations of transformed cells at low density tend to select against cell strains that are continous producers of infectious virus."}
{"id": "PMID:208962", "title": "A transitional cell carcinoma cell line.", "content": "A transitional cell carcinoma cell line, COLO 232, was derived from a primary urinary bladder tumor in a Caucasian male. In culture, COLO 232 retained distinct uroepithelial phenotypic traits and produced both carcinoembryonic antigen and adrenocorticotropic hormone. COLO 232 had a chromosome mode of 58 and retained the X and Y chromosomes. Ten marker chromosomes were identified. COLO 232 will be of value for biochemical and immunological studies.", "contents": "A transitional cell carcinoma cell line. A transitional cell carcinoma cell line, COLO 232, was derived from a primary urinary bladder tumor in a Caucasian male. In culture, COLO 232 retained distinct uroepithelial phenotypic traits and produced both carcinoembryonic antigen and adrenocorticotropic hormone. COLO 232 had a chromosome mode of 58 and retained the X and Y chromosomes. Ten marker chromosomes were identified. COLO 232 will be of value for biochemical and immunological studies."}
{"id": "PMID:208963", "title": "Effect of serum on cells cultured from human mammary tumors.", "content": "Clusters of cells derived from biopsy specimens of human mammary ductal carcinomas form two morphologically distinct epithelial colonies in culture, designated as E and E'. The proportion of E' cell clusters that attached and formed colonies ranged from 0.3 to 13.0% with different tumors. Attachment was independent of tumor grade. Microscopic observations revealed that the survival of E' cell colonies was limited to approximately 10 days with rapid cell degeneration commencing about 7 days. A comparison of sera showed that colony formation by cells from malignant tumors during the 1st week of culture was maximum in the presence of fetal bovine serum. Human serum alone was 70 to 100% less effective in promoting E' colonies. The most significant finding was that human serum from normal donors inhibited E' colony development in the presence of FBS. Although human serum was less effective than FBS in promoting colony formation by clusters of E cells, an inhibition was not observed. Inhibitory activity could not be attributed to either antagonistic hormones or the source of human serum. These results demonstrate that normal human serum contains a factor(s) that exhibits an inhibitory activity specific for human epithelial cells (E') derived from malignant tumors.", "contents": "Effect of serum on cells cultured from human mammary tumors. Clusters of cells derived from biopsy specimens of human mammary ductal carcinomas form two morphologically distinct epithelial colonies in culture, designated as E and E'. The proportion of E' cell clusters that attached and formed colonies ranged from 0.3 to 13.0% with different tumors. Attachment was independent of tumor grade. Microscopic observations revealed that the survival of E' cell colonies was limited to approximately 10 days with rapid cell degeneration commencing about 7 days. A comparison of sera showed that colony formation by cells from malignant tumors during the 1st week of culture was maximum in the presence of fetal bovine serum. Human serum alone was 70 to 100% less effective in promoting E' colonies. The most significant finding was that human serum from normal donors inhibited E' colony development in the presence of FBS. Although human serum was less effective than FBS in promoting colony formation by clusters of E cells, an inhibition was not observed. Inhibitory activity could not be attributed to either antagonistic hormones or the source of human serum. These results demonstrate that normal human serum contains a factor(s) that exhibits an inhibitory activity specific for human epithelial cells (E') derived from malignant tumors."}
{"id": "PMID:208964", "title": "Subclones of normal clonal prolactin cells of the rat.", "content": "We recently established a clone (2B8) of normal rat prolactin cells that secretes only prolactin into the medium. When grown in the presence of thyrotrophin-releasing hormone (TRH), estradiol (E2) or arginine vasotocin (AVT), the cells show increased production of prolactin. Subclones of single cell origin were developed from 2B8 cells exposed for 1 week to TRH, E2 or TRH plus E2. These subclones differ in their response to TRH, E2 or AVT and therefore may possess different receptors for these hormones.", "contents": "Subclones of normal clonal prolactin cells of the rat. We recently established a clone (2B8) of normal rat prolactin cells that secretes only prolactin into the medium. When grown in the presence of thyrotrophin-releasing hormone (TRH), estradiol (E2) or arginine vasotocin (AVT), the cells show increased production of prolactin. Subclones of single cell origin were developed from 2B8 cells exposed for 1 week to TRH, E2 or TRH plus E2. These subclones differ in their response to TRH, E2 or AVT and therefore may possess different receptors for these hormones."}
{"id": "PMID:208965", "title": "Isolation of function human trophoblast cells and their partial characterization in primary cell culture.", "content": "Human trophoblast isolation and cell culture procedures were examined to identify variables that enhance secretion of chorionic gonadotropin (HCG) in primary culture. Brief exposure of unminced first-trimester placental specimens to a solution of trypsin-EDTA-DNAse, and isolation of the dispersed cells after Ficoll-hypaque centrifugation yielded primary cultures that were high in HCG secretion and content of epithelial-like cells. The gradual decline in HCG level with time in monolayer culture in these presumptive trophoblast cells was retarded by treatment with theophylline and cyclic adenosine monophosphate. Exposure to methotrexate (MTX) did not increase HCG secretion in normal trophoblast cells, in contrast to a 5-fold stimulation by MTX in the JAR line of choriocarcinoma cells. Clusters of polygonal cells in primary culture progressively lost their capacity to secrete HCG and their epithelial-like morphology. However, they could be maintained as cell strains through approximately 15 passages over a period of 13 to 16 weeks.", "contents": "Isolation of function human trophoblast cells and their partial characterization in primary cell culture. Human trophoblast isolation and cell culture procedures were examined to identify variables that enhance secretion of chorionic gonadotropin (HCG) in primary culture. Brief exposure of unminced first-trimester placental specimens to a solution of trypsin-EDTA-DNAse, and isolation of the dispersed cells after Ficoll-hypaque centrifugation yielded primary cultures that were high in HCG secretion and content of epithelial-like cells. The gradual decline in HCG level with time in monolayer culture in these presumptive trophoblast cells was retarded by treatment with theophylline and cyclic adenosine monophosphate. Exposure to methotrexate (MTX) did not increase HCG secretion in normal trophoblast cells, in contrast to a 5-fold stimulation by MTX in the JAR line of choriocarcinoma cells. Clusters of polygonal cells in primary culture progressively lost their capacity to secrete HCG and their epithelial-like morphology. However, they could be maintained as cell strains through approximately 15 passages over a period of 13 to 16 weeks."}
{"id": "PMID:208968", "title": "Cell-mediated immunity assayed by 51Cr release test in mice infected with mouse adenovirus.", "content": "Immune spleen cells (ISC) from mice immunized with a sublethal dose of mouse adenovirus (M-Ad) were shown by the 51Cr release test to be cytotoxic to target mouse embryonic cells or lymphoid cells infected with M-Ad. The number of ISC required for release of statistically significant amounts of 51Cr from target cells varied from one sample to another, ranging from 5 to greater than or equal to 30 ISC per target cell. When 24-h-infected mouse embryonic cells were used as targets, the release of 51Cr became evident in 6 h after the addition of ISC to the cells, gradually increased with time, and then leveled off. Cytolytic activity of M-Ad ISC is specific for M-Ad, since ISC do not lyse mouse embryonic cells infected with human adenovirus type 12 and vice versa. Kinetic study of the development of cell-mediated immunity to M-Ad assayed by 51Cr release showed that cytolytic activity of ISC in infected mice became detectable 4 days postinfection, reached its peak level about 7 to 10 days postinfection, and fell to undetectable levels about 10 days thereafter. This is consistent with the data obtained by inhibition of intracellular viral antigen synthesis or by the macrophage migration inhibition test in our prevous reports.", "contents": "Cell-mediated immunity assayed by 51Cr release test in mice infected with mouse adenovirus. Immune spleen cells (ISC) from mice immunized with a sublethal dose of mouse adenovirus (M-Ad) were shown by the 51Cr release test to be cytotoxic to target mouse embryonic cells or lymphoid cells infected with M-Ad. The number of ISC required for release of statistically significant amounts of 51Cr from target cells varied from one sample to another, ranging from 5 to greater than or equal to 30 ISC per target cell. When 24-h-infected mouse embryonic cells were used as targets, the release of 51Cr became evident in 6 h after the addition of ISC to the cells, gradually increased with time, and then leveled off. Cytolytic activity of M-Ad ISC is specific for M-Ad, since ISC do not lyse mouse embryonic cells infected with human adenovirus type 12 and vice versa. Kinetic study of the development of cell-mediated immunity to M-Ad assayed by 51Cr release showed that cytolytic activity of ISC in infected mice became detectable 4 days postinfection, reached its peak level about 7 to 10 days postinfection, and fell to undetectable levels about 10 days thereafter. This is consistent with the data obtained by inhibition of intracellular viral antigen synthesis or by the macrophage migration inhibition test in our prevous reports."}
{"id": "PMID:208969", "title": "Small-plaque variant of canine herpesvirus with reduced pathogenicity for newborn pups.", "content": "The plaque characteristics of 13 field isolates of canine herpesvirus were found to be similar. After 312 passages of the F-205 strain in dog kidney cell cultures incubated at 35 degrees C, the virus still was virulent for newborn pups; it also had the macroplaque morphology of the wild-type virus. However, after 20 additional passages at 30 degrees C, a microplaque (mP) variant had emerged as the predominant type. Cloned mP virus retained the small-plaque characteristic after 66 transfers at 30 degrees C. The natural history of the mP strain and some of its biological properties are reported, the most significant being its lack of pathogenicity for newborn pups.", "contents": "Small-plaque variant of canine herpesvirus with reduced pathogenicity for newborn pups. The plaque characteristics of 13 field isolates of canine herpesvirus were found to be similar. After 312 passages of the F-205 strain in dog kidney cell cultures incubated at 35 degrees C, the virus still was virulent for newborn pups; it also had the macroplaque morphology of the wild-type virus. However, after 20 additional passages at 30 degrees C, a microplaque (mP) variant had emerged as the predominant type. Cloned mP virus retained the small-plaque characteristic after 66 transfers at 30 degrees C. The natural history of the mP strain and some of its biological properties are reported, the most significant being its lack of pathogenicity for newborn pups."}
{"id": "PMID:208970", "title": "Orofacial herpes simplex virus infection in hairless mice: latent virus in trigeminal ganglia after topical antiviral treatment.", "content": "Inoculation of herpes simplex virus on the forehead and/or snout of hairless mice resulted in a significantly lower mortality rate than inoculation of the skin in the lumbosacral area. Latent herpes simplex virus infections were detected in all forehead-inoculated and in 90% of snout-inoculated mice. Phosphonoacetic acid was highly effective in preventing the development of skin lesions, and no latent infections were detected when phosphonoacetic acid ointment was applied 3 h after infection. Neither adenine arabinoside nor adenine arabinoside monophosphate prevented the establishment of latent infections in the trigeminal ganglia, although they protected the mice from the fatal outcome of the infection. The antibody response after adenine arabinoside or adenine arabinoside monophosphate treatment was similar to that observed in untreated animals, and it was six to eight times higher than in mice treated with phosphonoacetic acid. Mice without evidence of latent infection had, in general, lower serum antibody titers than those with latent infections in the ganglia. An analysis of the pathogenesis of herpes simplex virus infection in mice treated with adenine arabinoside showed that virus penetration into the nerve endings was delayed and that the amount of free virus in ganglionic homogenates was 10 to 100 times less than that for untreated mice.", "contents": "Orofacial herpes simplex virus infection in hairless mice: latent virus in trigeminal ganglia after topical antiviral treatment. Inoculation of herpes simplex virus on the forehead and/or snout of hairless mice resulted in a significantly lower mortality rate than inoculation of the skin in the lumbosacral area. Latent herpes simplex virus infections were detected in all forehead-inoculated and in 90% of snout-inoculated mice. Phosphonoacetic acid was highly effective in preventing the development of skin lesions, and no latent infections were detected when phosphonoacetic acid ointment was applied 3 h after infection. Neither adenine arabinoside nor adenine arabinoside monophosphate prevented the establishment of latent infections in the trigeminal ganglia, although they protected the mice from the fatal outcome of the infection. The antibody response after adenine arabinoside or adenine arabinoside monophosphate treatment was similar to that observed in untreated animals, and it was six to eight times higher than in mice treated with phosphonoacetic acid. Mice without evidence of latent infection had, in general, lower serum antibody titers than those with latent infections in the ganglia. An analysis of the pathogenesis of herpes simplex virus infection in mice treated with adenine arabinoside showed that virus penetration into the nerve endings was delayed and that the amount of free virus in ganglionic homogenates was 10 to 100 times less than that for untreated mice."}
{"id": "PMID:208971", "title": "Loss on serial passage of rhesus monkey kidney cells of proteolytic activity required for Sendai virus activation.", "content": "Primary and secondary cultures of rhesus monkey kidney cells supported multiple-cycle replication of Sendai virus, but later passages lost this ability, and this was reflected in decreased plaque formation. Multiple-cycle replication also did not occur in LLC-MK2 cells, a continuous line of RMK cells. Failure of replication in serially passed cells was correlated with a decrease in proteolytic cleavage of a viral surface glycoprotein (Fo), and the ability of cells to support multiple-cycle replication and plaque formation could be restored by the addition of trypsin (0.3 microgram/ml) to the overlay medium. The use of wild-type virus, which requires trypsin, and protease activation mutants that require chymotrypsin or elastase for activation has provided evidence that the activating protease supplied by primary or secondary cells has trypsin-like activity. Inactive virus, with uncleaved Fo glycoprotein, absorbed to primary or secondary cells but did not infect them, even though such cells possess the enzyme that is capable of cleaving the Fo glycoprotein of virus synthesized in these cells. The inability of these cells to activate adsorbed virus indicates that the activating protease that they possess is inacessible to adsorbed virus, although it can act on the Fo glycoprotein during virus maturation in these cells. These data provide a biochemical explanation for the failure of later passages of a cell strain or a continuous cell line to support the replication of a paramyxovirus.", "contents": "Loss on serial passage of rhesus monkey kidney cells of proteolytic activity required for Sendai virus activation. Primary and secondary cultures of rhesus monkey kidney cells supported multiple-cycle replication of Sendai virus, but later passages lost this ability, and this was reflected in decreased plaque formation. Multiple-cycle replication also did not occur in LLC-MK2 cells, a continuous line of RMK cells. Failure of replication in serially passed cells was correlated with a decrease in proteolytic cleavage of a viral surface glycoprotein (Fo), and the ability of cells to support multiple-cycle replication and plaque formation could be restored by the addition of trypsin (0.3 microgram/ml) to the overlay medium. The use of wild-type virus, which requires trypsin, and protease activation mutants that require chymotrypsin or elastase for activation has provided evidence that the activating protease supplied by primary or secondary cells has trypsin-like activity. Inactive virus, with uncleaved Fo glycoprotein, absorbed to primary or secondary cells but did not infect them, even though such cells possess the enzyme that is capable of cleaving the Fo glycoprotein of virus synthesized in these cells. The inability of these cells to activate adsorbed virus indicates that the activating protease that they possess is inacessible to adsorbed virus, although it can act on the Fo glycoprotein during virus maturation in these cells. These data provide a biochemical explanation for the failure of later passages of a cell strain or a continuous cell line to support the replication of a paramyxovirus."}
{"id": "PMID:208972", "title": "Direct syncytial assay for the quantitation of bovine leukemia virus.", "content": "A direct in vitro tissue culture method is described for the quantitation of bovine leukemia virus, utlizing a feline S+L-- cell line.", "contents": "Direct syncytial assay for the quantitation of bovine leukemia virus. A direct in vitro tissue culture method is described for the quantitation of bovine leukemia virus, utlizing a feline S+L-- cell line."}
{"id": "PMID:208973", "title": "Effect of Mycobacterium tuberculosis BCG infection on the resistance of mice to ectromelia virus infection: participation of interferon in enhanced resistance.", "content": "Mice infected with Mycobacterium tuberculosis BCG were more resistant than normal mice to ectromelia virus infection. It is suggested that enhanced interferon production in peritoneal exudate cells and spleen cells of BCG-infected mice plays an important role in this resistance.", "contents": "Effect of Mycobacterium tuberculosis BCG infection on the resistance of mice to ectromelia virus infection: participation of interferon in enhanced resistance. Mice infected with Mycobacterium tuberculosis BCG were more resistant than normal mice to ectromelia virus infection. It is suggested that enhanced interferon production in peritoneal exudate cells and spleen cells of BCG-infected mice plays an important role in this resistance."}
{"id": "PMID:208974", "title": "In vitro establishment of Marek's disease herpesvirus-transformed productive and nonproductive lymphoblastoid cell lines.", "content": "The establishment of two Marek's disease herpesvirus-transformed lymphoblastoid cell lines (JMV-1 and JM-1) is reported. Cocultivation with chicken embryo fibroblasts, attempts to rescue Marek's disease virus from kidney cell cultures, and immunofluorescent staining show that JMV-1 is a nonproductive line and JM-1 is a productive line.", "contents": "In vitro establishment of Marek's disease herpesvirus-transformed productive and nonproductive lymphoblastoid cell lines. The establishment of two Marek's disease herpesvirus-transformed lymphoblastoid cell lines (JMV-1 and JM-1) is reported. Cocultivation with chicken embryo fibroblasts, attempts to rescue Marek's disease virus from kidney cell cultures, and immunofluorescent staining show that JMV-1 is a nonproductive line and JM-1 is a productive line."}
{"id": "PMID:208975", "title": "Bluetongue virus, an exceptionally potent interferon inducer in mice.", "content": "The attenuated American BT-8 strain of bluetongue virus is 5 to 10 times more potent an interferon inducer than any other viral or nonviral agent reported to date, including as much as 600,000 units/ml of plasma by 8 h after intravenous injection.", "contents": "Bluetongue virus, an exceptionally potent interferon inducer in mice. The attenuated American BT-8 strain of bluetongue virus is 5 to 10 times more potent an interferon inducer than any other viral or nonviral agent reported to date, including as much as 600,000 units/ml of plasma by 8 h after intravenous injection."}
{"id": "PMID:208976", "title": "Effect of zinc and calcium ions on the production of alpha-toxin and proteases by Clostridium perfringens.", "content": "Clostridium perfringens produced at least three distinct proteases in a synthetic medium containing calcium. Two of them, thiol and ethylenediaminetetraacetic acid disodium salt-sensitive proteases, appeared at an early stage of growth, but the other one, perhaps being identical to the one produced in a calcium-deficient medium, appeared at a late stage. The production of these proteases depended on Ca2+ but not on Zn2+ in the medium. Alpha-toxin, perhaps being a zinc-containing metalloenzyme, was rather resistant to the proteases, but toxin, produced in a zinc-deficient medium or deprived of zinc with ethylenediaminetetraacetic acid disodium salt, was very sensitive. By adding Zn2+, the toxin lacking zinc may have been converted to the zinc-containing metalloprotein that is resistant to proteases. This may explain why alpha-toxin activity increased progressively in a zinc-containing medium in spite of simultaneous production of potent proteases and why it disappeared rapidly in a zinc-deficient medium.", "contents": "Effect of zinc and calcium ions on the production of alpha-toxin and proteases by Clostridium perfringens. Clostridium perfringens produced at least three distinct proteases in a synthetic medium containing calcium. Two of them, thiol and ethylenediaminetetraacetic acid disodium salt-sensitive proteases, appeared at an early stage of growth, but the other one, perhaps being identical to the one produced in a calcium-deficient medium, appeared at a late stage. The production of these proteases depended on Ca2+ but not on Zn2+ in the medium. Alpha-toxin, perhaps being a zinc-containing metalloenzyme, was rather resistant to the proteases, but toxin, produced in a zinc-deficient medium or deprived of zinc with ethylenediaminetetraacetic acid disodium salt, was very sensitive. By adding Zn2+, the toxin lacking zinc may have been converted to the zinc-containing metalloprotein that is resistant to proteases. This may explain why alpha-toxin activity increased progressively in a zinc-containing medium in spite of simultaneous production of potent proteases and why it disappeared rapidly in a zinc-deficient medium."}
{"id": "PMID:208977", "title": "Properties of an Escherichia coli cytotoxin.", "content": "Isoelectric focusing of a heat-labile cytotoxin of Escherichia coli H30 revealed the presence of two molecular variants, pI 7.2 and a comparatively small quantity of pI 6.8. Predominant component pI 7.2 had a molecular weight of 28,000, induced some fluid accumulation in rabbit ileal loops, and showed no morphological response in Y-1 cells but a strong cytotoxic effect on Vero cells.", "contents": "Properties of an Escherichia coli cytotoxin. Isoelectric focusing of a heat-labile cytotoxin of Escherichia coli H30 revealed the presence of two molecular variants, pI 7.2 and a comparatively small quantity of pI 6.8. Predominant component pI 7.2 had a molecular weight of 28,000, induced some fluid accumulation in rabbit ileal loops, and showed no morphological response in Y-1 cells but a strong cytotoxic effect on Vero cells."}
{"id": "PMID:208978", "title": "Innate cytotoxicity of CBA mouse spleen cells to Sendai virus-infected L cells.", "content": "The presence in the spleens of unsensitized CBA mice of cells that are spontaneously cytotoxic for Sendai virus-infected L cells was confirmed. This innate cytotoxic activity to virus-infected cells was shown to exhibit some H-2 restriction. Partial identity of only the D end of the H-2 gene complex between the target and effector cells was required to produce cytolysis. Attempts to characterize the kind of cell active in this system indicated that neither the theta antigen nor the surface immunoglobulin markers were present. Furthermore, the cells appeared to have no adherent or phagocytic properties. The relationship between the effector cells responsible for innate cytotoxicity to virus-infected cells and the natural killer (NK) cells spontaneously cytotoxic for certain tumor cells is discussed.", "contents": "Innate cytotoxicity of CBA mouse spleen cells to Sendai virus-infected L cells. The presence in the spleens of unsensitized CBA mice of cells that are spontaneously cytotoxic for Sendai virus-infected L cells was confirmed. This innate cytotoxic activity to virus-infected cells was shown to exhibit some H-2 restriction. Partial identity of only the D end of the H-2 gene complex between the target and effector cells was required to produce cytolysis. Attempts to characterize the kind of cell active in this system indicated that neither the theta antigen nor the surface immunoglobulin markers were present. Furthermore, the cells appeared to have no adherent or phagocytic properties. The relationship between the effector cells responsible for innate cytotoxicity to virus-infected cells and the natural killer (NK) cells spontaneously cytotoxic for certain tumor cells is discussed."}
{"id": "PMID:208979", "title": "Proliferative and interferon responses by peripheral blood mononuclear cells after bone marrow transplantation in humans.", "content": "The capacity of peripheral blood mononuclear cells from bone marrow transplant recipients to proliferate and produce interferon in response to mitogens and specific antigens was tested. Proliferation in response to phytohemagglutinin or pokeweed mitogen occurred in cells from more than 90% of the recipients, and interferon was present in 60 to 70% of the supernatants from these cultures, even when tested as soon as 8 weeks after transplantation. Proliferation in response to bacterial antigens was infrequent, and interferon release was not detected. In the early post-transplantation period (less than 13 weeks), cells from only two of four cytomegalovirus (CMV) antibody-positive patients proliferated normally in response to CMV antigen and interferon release was detected only once. In the late post-transplantation period (more than 13 weeks), in only two of five instances did cells proliferating in response to CMV antigen release interferon. The response to CMV antigen of mononuclear cells from many transplant recipients differs from that of cells from normal controls.", "contents": "Proliferative and interferon responses by peripheral blood mononuclear cells after bone marrow transplantation in humans. The capacity of peripheral blood mononuclear cells from bone marrow transplant recipients to proliferate and produce interferon in response to mitogens and specific antigens was tested. Proliferation in response to phytohemagglutinin or pokeweed mitogen occurred in cells from more than 90% of the recipients, and interferon was present in 60 to 70% of the supernatants from these cultures, even when tested as soon as 8 weeks after transplantation. Proliferation in response to bacterial antigens was infrequent, and interferon release was not detected. In the early post-transplantation period (less than 13 weeks), cells from only two of four cytomegalovirus (CMV) antibody-positive patients proliferated normally in response to CMV antigen and interferon release was detected only once. In the late post-transplantation period (more than 13 weeks), in only two of five instances did cells proliferating in response to CMV antigen release interferon. The response to CMV antigen of mononuclear cells from many transplant recipients differs from that of cells from normal controls."}
{"id": "PMID:208980", "title": "Replication of dengue and junin viruses in cultured rabbit and human endothelial cells.", "content": "The flavivirus dengue and the arenavirus Junin are both associated with a hemorrhagic shock syndrome in man. We have demonstrated the replication of these viruses in vitro in both rabbit and human endothelial cells by viral titers and immunofluorescent antibody studies. Rabbit endothelium established in continuous culture was derived from vena cava, while human cells in primary culture were derived from umbilical veins. In rabbit endothelium, dengue-2 virus passaged through monkey kidney monolayer cells (LLC-MK2) or human lymphoblastoid cells (raji) produced significantly more virus than the seed obtained from suckling mouse brain (MB). Inoculation of actively dividing, subconfluent human endothelial cells with the LLC-MK2 degue virus produced higher viral titers than inoculation of confluent cells. The appearance of Junin virus was delayed beyond that of dengue virus in rabbit endothelial cells although equivalent titers of virus were produced. In human cells, Junin virus was less productive than dengue virus and produced characteristic cycles of virus release. This is the first direct evidence for replication of human hemorrhagic fever viruses in endothelial cells.", "contents": "Replication of dengue and junin viruses in cultured rabbit and human endothelial cells. The flavivirus dengue and the arenavirus Junin are both associated with a hemorrhagic shock syndrome in man. We have demonstrated the replication of these viruses in vitro in both rabbit and human endothelial cells by viral titers and immunofluorescent antibody studies. Rabbit endothelium established in continuous culture was derived from vena cava, while human cells in primary culture were derived from umbilical veins. In rabbit endothelium, dengue-2 virus passaged through monkey kidney monolayer cells (LLC-MK2) or human lymphoblastoid cells (raji) produced significantly more virus than the seed obtained from suckling mouse brain (MB). Inoculation of actively dividing, subconfluent human endothelial cells with the LLC-MK2 degue virus produced higher viral titers than inoculation of confluent cells. The appearance of Junin virus was delayed beyond that of dengue virus in rabbit endothelial cells although equivalent titers of virus were produced. In human cells, Junin virus was less productive than dengue virus and produced characteristic cycles of virus release. This is the first direct evidence for replication of human hemorrhagic fever viruses in endothelial cells."}
{"id": "PMID:208981", "title": "Characterization of the TO strains of Theiler's mouse encephalomyelitis viruses.", "content": "Theiler's mouse encephalomyelitis virus isolates from the central nervous systems of spontaneously paralyzed mice and stools of asymptomatic mice resemble Theiler's original virus isolates. In this study four such strains were adapted by blind subpassage to replicate and to produce cytopathic effect in cell culture. These viruses were then found to be closely related to each other and to GDVII virus by cross-neutralization and to form small plaques. Bovine serum was found to contain cross-reacting antibodies to these viruses.", "contents": "Characterization of the TO strains of Theiler's mouse encephalomyelitis viruses. Theiler's mouse encephalomyelitis virus isolates from the central nervous systems of spontaneously paralyzed mice and stools of asymptomatic mice resemble Theiler's original virus isolates. In this study four such strains were adapted by blind subpassage to replicate and to produce cytopathic effect in cell culture. These viruses were then found to be closely related to each other and to GDVII virus by cross-neutralization and to form small plaques. Bovine serum was found to contain cross-reacting antibodies to these viruses."}
{"id": "PMID:208982", "title": "Mouse natural killer (NK) cell activity against human cell lines is not influenced by superinfection of the target cell with xenotropic murine C-type virus.", "content": "Mouse natural killer (NK) cells can lyse a variety of syngeneic, allogeneic and xenogeneic target cells in short-term 51Cr release assays. The target specificity of NK cells is not known, but endogenous C-type viral antigens have been suggested as possible target structures. To test this hypothesis, human lymphoid lines were superinfected with xenotropic mouse C-type virus either by repeated dosage through nude mice or by in vitro superinfection with the supernatants of nude-mouse-passaged lines. The appearance of surface-associated MuLV antigens after superinfection was confirmed in a complement-dependent cytotoxicity test. Subsequently, the NK sensitivity of each infected line was compared with its non-infected counterpart in direct cytolytic and competition assays. None of these two assay systems showed a consistent difference in NK sensitivity of infected and non-infected cell lines. These findings do not lend support to the concept tht murine C-type viral antigens are responsible for NK sensitivity.", "contents": "Mouse natural killer (NK) cell activity against human cell lines is not influenced by superinfection of the target cell with xenotropic murine C-type virus. Mouse natural killer (NK) cells can lyse a variety of syngeneic, allogeneic and xenogeneic target cells in short-term 51Cr release assays. The target specificity of NK cells is not known, but endogenous C-type viral antigens have been suggested as possible target structures. To test this hypothesis, human lymphoid lines were superinfected with xenotropic mouse C-type virus either by repeated dosage through nude mice or by in vitro superinfection with the supernatants of nude-mouse-passaged lines. The appearance of surface-associated MuLV antigens after superinfection was confirmed in a complement-dependent cytotoxicity test. Subsequently, the NK sensitivity of each infected line was compared with its non-infected counterpart in direct cytolytic and competition assays. None of these two assay systems showed a consistent difference in NK sensitivity of infected and non-infected cell lines. These findings do not lend support to the concept tht murine C-type viral antigens are responsible for NK sensitivity."}
{"id": "PMID:208983", "title": "Differential growth and transmission in cats of feline leukaemia viruses of subgroups A and B.", "content": "The outcome of infecting cats with FeLV of sub-groups A (FeLV-A) or B (FeLV-B) was different. After FeLV-A infection, virus was quickly recovered from the blood and oropharynx of most animals. Following infection with FeLV-B, only a small proportion of cats developed a viraemia, and this after a long interval. There was no evidence that FeLV-B was transmitted by contact. The result of infecting cats with mixtures of FeLV-A and B (FeLV-AB) was that to a large extent each virus operated independently. FeLV-A was recovered from the plasma first, in a high proportion of the cats, and FeLV-B appeared later but not in all cats. There was evidence of interaction, however, in that the proportion of cats which were viraemic with FeLV-B was greater following FeLV-AB infection than after infection with FeLV-B alone; also FeLV-B was transmitted by contact from cats excreting FeLV-AB. These results help to explain the apparent dependence of FeLV-B on FeLV-A under natural conditions and the frequency of occurrence of sugroups A and B in FeLV isolates.", "contents": "Differential growth and transmission in cats of feline leukaemia viruses of subgroups A and B. The outcome of infecting cats with FeLV of sub-groups A (FeLV-A) or B (FeLV-B) was different. After FeLV-A infection, virus was quickly recovered from the blood and oropharynx of most animals. Following infection with FeLV-B, only a small proportion of cats developed a viraemia, and this after a long interval. There was no evidence that FeLV-B was transmitted by contact. The result of infecting cats with mixtures of FeLV-A and B (FeLV-AB) was that to a large extent each virus operated independently. FeLV-A was recovered from the plasma first, in a high proportion of the cats, and FeLV-B appeared later but not in all cats. There was evidence of interaction, however, in that the proportion of cats which were viraemic with FeLV-B was greater following FeLV-AB infection than after infection with FeLV-B alone; also FeLV-B was transmitted by contact from cats excreting FeLV-AB. These results help to explain the apparent dependence of FeLV-B on FeLV-A under natural conditions and the frequency of occurrence of sugroups A and B in FeLV isolates."}
{"id": "PMID:208984", "title": "Genetic transmission of mammary tumour virus in the DBAf mouse strain.", "content": "MTV antigens were demonstrable by radioimmunoassay in milk samples from individual DBAf mice, and in samples from (male BALB/c X female DBAf) F1 mice. Although some samples collected during the first lactation periods of these mice were virus-negative, all samples of later lactation periods were virus-positive. From 75 mice of the [ male BALB/c X female (male BALB/c X female DBAf)]Bc I population, milk samples were collected during one or more lactation periods and tested for the presence of viral antigens; the samples of 42 mice were virus-positive. In the ([BALB/c X (BALB/c X DBAf)] X BALB/c)Bc II population two groups were distinguished. In the first group, the progeny of virus-positive Bc I mothers, 37 out of 62 mice had detectable levels of viral antigen in the milk. None of the 43 samples from mice of the second group, derived from MTV-negative Bc I females, were virus-positive. These data suggest that the presence of viral antigens in the milk of DBAf mice is controlled by a single dominant gene; evidence for linkage of this gene and the albino locus was obtained (recombination percentage: 20).", "contents": "Genetic transmission of mammary tumour virus in the DBAf mouse strain. MTV antigens were demonstrable by radioimmunoassay in milk samples from individual DBAf mice, and in samples from (male BALB/c X female DBAf) F1 mice. Although some samples collected during the first lactation periods of these mice were virus-negative, all samples of later lactation periods were virus-positive. From 75 mice of the [ male BALB/c X female (male BALB/c X female DBAf)]Bc I population, milk samples were collected during one or more lactation periods and tested for the presence of viral antigens; the samples of 42 mice were virus-positive. In the ([BALB/c X (BALB/c X DBAf)] X BALB/c)Bc II population two groups were distinguished. In the first group, the progeny of virus-positive Bc I mothers, 37 out of 62 mice had detectable levels of viral antigen in the milk. None of the 43 samples from mice of the second group, derived from MTV-negative Bc I females, were virus-positive. These data suggest that the presence of viral antigens in the milk of DBAf mice is controlled by a single dominant gene; evidence for linkage of this gene and the albino locus was obtained (recombination percentage: 20)."}
{"id": "PMID:208985", "title": "Circulating immune complexes in rats bearing chemically induced tumors. I. Sequential determination during the growth of tumours at various body sites.", "content": "Circulating immune complexes were measured in sequential monitoring studies in rats bearing chemically induced tumours at different body sites. The assay employed were based upon radioimmunoprecipitation of serum factors with 125I-C1q or with an indirect test whereby the inhibition of binding of 125I-C1q to IgG aggregates by tumour-bearer sera was measured. 125I-C1q-binding immune complexes were detected at the initial phase of tumour growth and the level of this activity returned to the normal range after tumour excision. With tumour growing at subcutaneous sites or in th peritoneal cavity, serum-borne C1q-binding material, after reaching a maximum level, decreased despite tumour progression and eventually fell into sub-normal ranges at terminal stages of growth. In contrast, following intravenous tumour cell injection, immune-complex levels increased until terminal stages of disease. The present findings indicate that the measurement of C1q-binding serum factors represents a useful method for monitoring the growth and burden of experimental animal tumours.", "contents": "Circulating immune complexes in rats bearing chemically induced tumors. I. Sequential determination during the growth of tumours at various body sites. Circulating immune complexes were measured in sequential monitoring studies in rats bearing chemically induced tumours at different body sites. The assay employed were based upon radioimmunoprecipitation of serum factors with 125I-C1q or with an indirect test whereby the inhibition of binding of 125I-C1q to IgG aggregates by tumour-bearer sera was measured. 125I-C1q-binding immune complexes were detected at the initial phase of tumour growth and the level of this activity returned to the normal range after tumour excision. With tumour growing at subcutaneous sites or in th peritoneal cavity, serum-borne C1q-binding material, after reaching a maximum level, decreased despite tumour progression and eventually fell into sub-normal ranges at terminal stages of growth. In contrast, following intravenous tumour cell injection, immune-complex levels increased until terminal stages of disease. The present findings indicate that the measurement of C1q-binding serum factors represents a useful method for monitoring the growth and burden of experimental animal tumours."}
{"id": "PMID:208986", "title": "Neoplastic transformation of hamster brain cells in vitro by polyoma virus.", "content": "The transformation of cultivated hamster brain cells by polyoma virus is reported. The transformed cell line contained polyoma virus-specific nuclear, surface and transplantation antigens. Subcutaneous and intracranial inoculations revealed high tumorigenicity of the cells. Brain-specific S 100 protein was found in these tumors with immuno-peroxidase staining, suggesting that they were of a nervous nature. Both in vivo and in vitro, the cells had glial features as studied by phase contrast, light and electron microscopy. Type-H virus-like particles were found in the tumor cells and might have played a role in the viral transformation.", "contents": "Neoplastic transformation of hamster brain cells in vitro by polyoma virus. The transformation of cultivated hamster brain cells by polyoma virus is reported. The transformed cell line contained polyoma virus-specific nuclear, surface and transplantation antigens. Subcutaneous and intracranial inoculations revealed high tumorigenicity of the cells. Brain-specific S 100 protein was found in these tumors with immuno-peroxidase staining, suggesting that they were of a nervous nature. Both in vivo and in vitro, the cells had glial features as studied by phase contrast, light and electron microscopy. Type-H virus-like particles were found in the tumor cells and might have played a role in the viral transformation."}
{"id": "PMID:208987", "title": "Search for infective mammalian type-C virus-related genes in the DNA of human sarcomas and leukemias.", "content": "DNA was extracted from two human sarcoma cell lines, TE-32 and TE-418, and the leukemic cells from five children with acute myelocytic leukemia, three children with acute lymphocytic leukemia and four adults with acute myelocytic leukemia. The DNAs, assayed for infectivity by transfection techniques, induced no measurable virus by methods which would detect known mammalian C-type antigens or RNA-directed DNA polymerase in TE-32, D-17 dog cells and other indicator cells, nor did they recombine with or rescue endogenous human or exogenous murine or baboon type-C virus. Model systems used as controls were human sarcoma cells, TE-32 and HT-1080, and human lymphoma cells TE-543, experimentally infected with KiMuLV, GaLV or baboon type-C virus, all of which released infectious virus and whose DNAs were infectious for TE-32 and D-17 dog cells. Other model systems included two baboon placentas and one embryonic cell strain spontaneously releasing infectious endogenous baboon virus and yielding DNAs infectious for D-17 dog cells but not for TE-32 cells. Four other baboon embryonic tissues and two embryonic cell strains, releasing either low levels of virus or no virus, did not yield infectious DNA.", "contents": "Search for infective mammalian type-C virus-related genes in the DNA of human sarcomas and leukemias. DNA was extracted from two human sarcoma cell lines, TE-32 and TE-418, and the leukemic cells from five children with acute myelocytic leukemia, three children with acute lymphocytic leukemia and four adults with acute myelocytic leukemia. The DNAs, assayed for infectivity by transfection techniques, induced no measurable virus by methods which would detect known mammalian C-type antigens or RNA-directed DNA polymerase in TE-32, D-17 dog cells and other indicator cells, nor did they recombine with or rescue endogenous human or exogenous murine or baboon type-C virus. Model systems used as controls were human sarcoma cells, TE-32 and HT-1080, and human lymphoma cells TE-543, experimentally infected with KiMuLV, GaLV or baboon type-C virus, all of which released infectious virus and whose DNAs were infectious for TE-32 and D-17 dog cells. Other model systems included two baboon placentas and one embryonic cell strain spontaneously releasing infectious endogenous baboon virus and yielding DNAs infectious for D-17 dog cells but not for TE-32 cells. Four other baboon embryonic tissues and two embryonic cell strains, releasing either low levels of virus or no virus, did not yield infectious DNA."}
{"id": "PMID:208989", "title": "Activation of endogenous type-C viral p30 antigen in chemically-induced rat hepatocellular carcinomas.", "content": "Chemically induced rat hepatocellular carcinomas were prospectively examined for expression of the major group-specific antigen (p 30) of genetically transmitted rat type-C viruses. Ten primary tumors induced following oral administration of the carcinogen N-2-acetylaminofluorine did not express elevated levels of viral antigen as compared to antigen levels detected in normal liver tissue. By contrast, rapidly growing transplantable hepatocellular carcinomas (THCs) derived from primary tumor expressed increased quantities of viral antigen. The expression of antigen was marginally elevated after only one transplanation, increased to maximal levels after several transplant generations and, once achieved, was stably maintained throughout subsequent transplants. Studies with additional previously established THCs showed that poorly differentiated, rapidly proliferating tumors tended to express elevated levels of viral antigen, while more differentiated, slowly growing tumors did not. The results show that the expression of endogenous type-C viral 30 antigen is a stable phenotypic property of many rat THC lines.", "contents": "Activation of endogenous type-C viral p30 antigen in chemically-induced rat hepatocellular carcinomas. Chemically induced rat hepatocellular carcinomas were prospectively examined for expression of the major group-specific antigen (p 30) of genetically transmitted rat type-C viruses. Ten primary tumors induced following oral administration of the carcinogen N-2-acetylaminofluorine did not express elevated levels of viral antigen as compared to antigen levels detected in normal liver tissue. By contrast, rapidly growing transplantable hepatocellular carcinomas (THCs) derived from primary tumor expressed increased quantities of viral antigen. The expression of antigen was marginally elevated after only one transplanation, increased to maximal levels after several transplant generations and, once achieved, was stably maintained throughout subsequent transplants. Studies with additional previously established THCs showed that poorly differentiated, rapidly proliferating tumors tended to express elevated levels of viral antigen, while more differentiated, slowly growing tumors did not. The results show that the expression of endogenous type-C viral 30 antigen is a stable phenotypic property of many rat THC lines."}
{"id": "PMID:208990", "title": "Further characterization of a herpesvirus-positive orang-utan cell line and comparative aspects of in vitro transformation with lymphotropic old world primate herpesviruses.", "content": "An orang-utan (Pongo pygmaeus) suspension line, CP81, was shown to lack myeloid markers of lysozyme activity an d phagocytosis but to be positive for lymphocytic N-alkaline phosphatase activity, and to release a B-cell-tropic herpesvirus. This herpesvirus, termed Herpesvirus pongo, had 30--40% DNA homology with EBV and was present at 2-3 genome copies per CP-81 cell. Gibbon lymphocytes transformed by H. pongo, Epstein-Barr virus (EBV), and H. papio (of baboon, Papio hamadryas, origin) were found to be virus antigen-positive B cells. Gibbon lymphocytes transformed by H. pongo and EBV and transplanted to nude mice by the intracranial (IC) route (had a 75% and a 45% success rate, respectively), while transplants of similar cells transformed by H. papio were only 10% successful. None of these lines transplanted subcutaneously (SC) nor manifested a high degree of colony formation in 0.33% agarose (less than or equal to 0.5%), Gibbon lymphocytes transformed by H. pongo were hypodiploid while those transformed by EBV or H. papio were diploid. CP-81 cells themselves could be transplanted both IC (100%) and SC (70%) and showed a relatively high degree of colony formation in agarose (6.4-7.6%). B95-8 cells (marmoset, Saguinus oedipus-EBV) could be transplanted IC (66%) but not SC and had a low but significant ability to grow in agarose (1.6%). 594S (baboon, P. hamadryas-H. papio) cells could be transplanted IC (25%) but not SC, and grew to very low levels in agarose (0.1%).", "contents": "Further characterization of a herpesvirus-positive orang-utan cell line and comparative aspects of in vitro transformation with lymphotropic old world primate herpesviruses. An orang-utan (Pongo pygmaeus) suspension line, CP81, was shown to lack myeloid markers of lysozyme activity an d phagocytosis but to be positive for lymphocytic N-alkaline phosphatase activity, and to release a B-cell-tropic herpesvirus. This herpesvirus, termed Herpesvirus pongo, had 30--40% DNA homology with EBV and was present at 2-3 genome copies per CP-81 cell. Gibbon lymphocytes transformed by H. pongo, Epstein-Barr virus (EBV), and H. papio (of baboon, Papio hamadryas, origin) were found to be virus antigen-positive B cells. Gibbon lymphocytes transformed by H. pongo and EBV and transplanted to nude mice by the intracranial (IC) route (had a 75% and a 45% success rate, respectively), while transplants of similar cells transformed by H. papio were only 10% successful. None of these lines transplanted subcutaneously (SC) nor manifested a high degree of colony formation in 0.33% agarose (less than or equal to 0.5%), Gibbon lymphocytes transformed by H. pongo were hypodiploid while those transformed by EBV or H. papio were diploid. CP-81 cells themselves could be transplanted both IC (100%) and SC (70%) and showed a relatively high degree of colony formation in agarose (6.4-7.6%). B95-8 cells (marmoset, Saguinus oedipus-EBV) could be transplanted IC (66%) but not SC and had a low but significant ability to grow in agarose (1.6%). 594S (baboon, P. hamadryas-H. papio) cells could be transplanted IC (25%) but not SC, and grew to very low levels in agarose (0.1%)."}
{"id": "PMID:208991", "title": "The specificity of neutralizing antibodies to feline leukaemia viruses.", "content": "Feline leukaemia viruses (FeLV) of subgroups A (FeLV-A), B(FeLV-B) and C(FeLV-C) were examined by neutralization. The FeLV-A isolates were monotypic. By contrast, there was antigenic variation within subgroups B and C. There was also considerable cross-reactivity between subgroups. Thus, FeLV-A viruses showed weak cross-reactivity to the standard FeLV-C isolate; four of the subgroup B viruses were identical and cross-reactied with the standard FeLV-C, but not with FeLV-A or the fifth FeLV-B, and this latter virus weakly cros-reacted with FeLV-A but not with the FeLV-C; within subgroup C, one virus was indistinguishable from the standard FeLV-C strain but the other two were very similar to FeLV-A. Therefore, subgroup classification based on interference did not altogether correspond with neutralizing behaviour for subgroups B and C.", "contents": "The specificity of neutralizing antibodies to feline leukaemia viruses. Feline leukaemia viruses (FeLV) of subgroups A (FeLV-A), B(FeLV-B) and C(FeLV-C) were examined by neutralization. The FeLV-A isolates were monotypic. By contrast, there was antigenic variation within subgroups B and C. There was also considerable cross-reactivity between subgroups. Thus, FeLV-A viruses showed weak cross-reactivity to the standard FeLV-C isolate; four of the subgroup B viruses were identical and cross-reactied with the standard FeLV-C, but not with FeLV-A or the fifth FeLV-B, and this latter virus weakly cros-reacted with FeLV-A but not with the FeLV-C; within subgroup C, one virus was indistinguishable from the standard FeLV-C strain but the other two were very similar to FeLV-A. Therefore, subgroup classification based on interference did not altogether correspond with neutralizing behaviour for subgroups B and C."}
{"id": "PMID:208992", "title": "Reaching problem-drinking Blacks: the unheralded potential of drinking driver programs.", "content": "The potential of court-enforced treatment of problem drinking drivers in reaching and effectively treating problem drinking Blacks is examined through an analysis of the experience of one such drinking driver program. The findings support the contention that the potential of court-enforced treatment is significant and should not be overlooked in any plan aimed at providing treatment services to the Black community.", "contents": "Reaching problem-drinking Blacks: the unheralded potential of drinking driver programs. The potential of court-enforced treatment of problem drinking drivers in reaching and effectively treating problem drinking Blacks is examined through an analysis of the experience of one such drinking driver program. The findings support the contention that the potential of court-enforced treatment is significant and should not be overlooked in any plan aimed at providing treatment services to the Black community."}
{"id": "PMID:208993", "title": "Demonstration of two different types of beta1-receptors in man (selective blockade of the positively inotropic and the positively chronotropic effect of isoproterenol).", "content": "The hemodynamic effect of a beta-receptor blockade with mepindolol--a noncardioselective beta-receptor blocker--was studied in 6 male test subjects age 25 to 30 years with an increasing dose of isoproterenol. The cardiac output per min, the heart rate and the stroke volume, the wet blood pressure and the contractility parameters dp/dt max in the right and left ventricles were measured as part of the study. It was found that a dissociated right shift of the dose-effect curves occurred for the stroke volume, contractility parameters and heart rate. The following major conclusions can be made from an exact analysis of this result: 1. Evidence was produced that a distinction must be made in man with respect to the so-called beta1-receptors between those which mediate a specific effect on the heart rate and those which mediate a primarily positively inotropic effect. 2. There are apparently some beta-receptor blockers which inhibit the frequency receptors primarily and the inotropic receptors to a lesser extent. 3. Through their beta 2-effect, noncardioselective beta-receptor blockers can partly compensate for their negatively inotropic effect on the heart by maintaining the Frank Starling mechanism.", "contents": "Demonstration of two different types of beta1-receptors in man (selective blockade of the positively inotropic and the positively chronotropic effect of isoproterenol). The hemodynamic effect of a beta-receptor blockade with mepindolol--a noncardioselective beta-receptor blocker--was studied in 6 male test subjects age 25 to 30 years with an increasing dose of isoproterenol. The cardiac output per min, the heart rate and the stroke volume, the wet blood pressure and the contractility parameters dp/dt max in the right and left ventricles were measured as part of the study. It was found that a dissociated right shift of the dose-effect curves occurred for the stroke volume, contractility parameters and heart rate. The following major conclusions can be made from an exact analysis of this result: 1. Evidence was produced that a distinction must be made in man with respect to the so-called beta1-receptors between those which mediate a specific effect on the heart rate and those which mediate a primarily positively inotropic effect. 2. There are apparently some beta-receptor blockers which inhibit the frequency receptors primarily and the inotropic receptors to a lesser extent. 3. Through their beta 2-effect, noncardioselective beta-receptor blockers can partly compensate for their negatively inotropic effect on the heart by maintaining the Frank Starling mechanism."}
{"id": "PMID:208995", "title": "Studies on the retina and the pigment epithelium in hereditary canine ceroid lipofuscinosis. II. The subcellular distribution of lysosomal hydrolases and other enzymes.", "content": "Observations on the progressive course of retinal degeneration in canine ceroid lipofuscinosis (CCL) showed dramatic changes in enzyme activity and subcellular compartmentation. Thus, in affected animals, a new particle containing high levels of hexosaminidase and galactosidase was found in fractions lighter than seen in controls. In the later stages of disease and in normal aging, a progressive increase in dense fractions with high titers of acid lipase and acid phosphatase was observed. Peroxidase was found predominantly in the heavier fractions (1.24 to 1.28 gm/ml) and was lower than normal in affected retina and RPE. These fractions were located above the pigment granule fraction. Changes of peroxidase activity in the pigment granules were age dependent in controls, but a decrease of similar magnitude occurred much earlier in affected dogs. The accumulation of large numbers of dense bodies in the retina and RPE in CCL may indicate an impairment of intracellular digestive mechanisms. The early and marked reduction of peroxidase activity in affected dogs is an important indicator for major changes in the biochemistry of the entire eye in this disease. Therefore the initial pathogenic event seems to be the inability of affected cells to cope with peroxidative damage at an early stage, followed by an exaggerated attempt by the cells to digest accumulating lipopigments.", "contents": "Studies on the retina and the pigment epithelium in hereditary canine ceroid lipofuscinosis. II. The subcellular distribution of lysosomal hydrolases and other enzymes. Observations on the progressive course of retinal degeneration in canine ceroid lipofuscinosis (CCL) showed dramatic changes in enzyme activity and subcellular compartmentation. Thus, in affected animals, a new particle containing high levels of hexosaminidase and galactosidase was found in fractions lighter than seen in controls. In the later stages of disease and in normal aging, a progressive increase in dense fractions with high titers of acid lipase and acid phosphatase was observed. Peroxidase was found predominantly in the heavier fractions (1.24 to 1.28 gm/ml) and was lower than normal in affected retina and RPE. These fractions were located above the pigment granule fraction. Changes of peroxidase activity in the pigment granules were age dependent in controls, but a decrease of similar magnitude occurred much earlier in affected dogs. The accumulation of large numbers of dense bodies in the retina and RPE in CCL may indicate an impairment of intracellular digestive mechanisms. The early and marked reduction of peroxidase activity in affected dogs is an important indicator for major changes in the biochemistry of the entire eye in this disease. Therefore the initial pathogenic event seems to be the inability of affected cells to cope with peroxidative damage at an early stage, followed by an exaggerated attempt by the cells to digest accumulating lipopigments."}
{"id": "PMID:208996", "title": "Association of cytomegalovirus (CMV) infection with cervical cancer: isolation of CMV from cell cultures derived from cervical biopsy.", "content": "Cytomegalovirus (CMV) was isolated from cell cultures derived from 2 of 10 cervical cancer biopsies from patients in an advanced stage of the disease. Five serial passages were necessary before extensive cytopathic changes characteristic of CMV infection appeared. All patients tested had complement-fixing antibodies to both isolates in higher titers than to the prototype AD169 strain. 6 of 8 patients tested also had herpesvirus type 2 antibodies.", "contents": "Association of cytomegalovirus (CMV) infection with cervical cancer: isolation of CMV from cell cultures derived from cervical biopsy. Cytomegalovirus (CMV) was isolated from cell cultures derived from 2 of 10 cervical cancer biopsies from patients in an advanced stage of the disease. Five serial passages were necessary before extensive cytopathic changes characteristic of CMV infection appeared. All patients tested had complement-fixing antibodies to both isolates in higher titers than to the prototype AD169 strain. 6 of 8 patients tested also had herpesvirus type 2 antibodies."}
{"id": "PMID:208997", "title": "Tumor induction in newborn and adult Syrian hamsters infected with SV40 temperature-sensitive 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. Wild-type SV40 and ts B201 were highly oncogenic for newborn but not adult animals; ts A239, ts A30 and ts BC210 also induced tumors in some adult hamsters. Unexpectedly, the number of tumors induced by ts A209 and ts A239 in newborn animals was very low. The number of tumors observed was also low in adults infected with ts A30, ts A239 and ts BC210. The duration of the latent period of tumors induced in adult animals was the same as in the newborns. The data obtained are discussed in connection with the defectiveness of the mutants to induce tumor-specific transplantation antigen activity in hamster cells.", "contents": "Tumor induction in newborn and adult Syrian hamsters infected with SV40 temperature-sensitive mutants. Newborn and adult Syrian hamsters were injected with wild-type SV40 and its temperature-sensitive (ts) mutants A30, A209, A239, B201 and BC210. Wild-type SV40 and ts B201 were highly oncogenic for newborn but not adult animals; ts A239, ts A30 and ts BC210 also induced tumors in some adult hamsters. Unexpectedly, the number of tumors induced by ts A209 and ts A239 in newborn animals was very low. The number of tumors observed was also low in adults infected with ts A30, ts A239 and ts BC210. The duration of the latent period of tumors induced in adult animals was the same as in the newborns. The data obtained are discussed in connection with the defectiveness of the mutants to induce tumor-specific transplantation antigen activity in hamster cells."}
{"id": "PMID:208998", "title": "Inhibition of DNA metabolism in human B lymphocytes by a substrain of Epstein-Barr virus (P3HR-1): a method for virus quantitation.", "content": "Pretreatment with the P3HR-1 substrain of Epstein-Barr virus (EBV) inhibited approximately 85% of the DNA stimulation induced by Staphylococcus aureus in human B lymphocytes. In parallel experiments, the DNA stimulation induced by the transforming B95-8 substrain of EBV was almost completely inhibited by prior exposure to P3HR-1 virus. Phytohemagglutinin stimulation was only slightly inhibited, whereas the DNA synthesis of continuously growing Raji cells was inhibited to a considerable extent. The degree of DNA inhibition was correlated with the induction of the EBV-determined antigens (membrane, early, and nuclear antigens) in sensitive indicator cells.", "contents": "Inhibition of DNA metabolism in human B lymphocytes by a substrain of Epstein-Barr virus (P3HR-1): a method for virus quantitation. Pretreatment with the P3HR-1 substrain of Epstein-Barr virus (EBV) inhibited approximately 85% of the DNA stimulation induced by Staphylococcus aureus in human B lymphocytes. In parallel experiments, the DNA stimulation induced by the transforming B95-8 substrain of EBV was almost completely inhibited by prior exposure to P3HR-1 virus. Phytohemagglutinin stimulation was only slightly inhibited, whereas the DNA synthesis of continuously growing Raji cells was inhibited to a considerable extent. The degree of DNA inhibition was correlated with the induction of the EBV-determined antigens (membrane, early, and nuclear antigens) in sensitive indicator cells."}
{"id": "PMID:208999", "title": "Mouse hepatitis virus strain MHV-S: formation of pseudotypes with a murine leukemia virus envelope.", "content": "Mouse hepatitis virus strain MHV-S forms pseudotype virions enveloped with Friend leukemia virus material when propagated in SRCDF1 DBT cells persistently infected with Friend leukemia virus.", "contents": "Mouse hepatitis virus strain MHV-S: formation of pseudotypes with a murine leukemia virus envelope. Mouse hepatitis virus strain MHV-S forms pseudotype virions enveloped with Friend leukemia virus material when propagated in SRCDF1 DBT cells persistently infected with Friend leukemia virus."}
{"id": "PMID:209000", "title": "Polyploidization of Epstein-Barr virus (EBV)-carrying lymphoma lines decreases the inducibility of EBV-determined early antigen following P3HR-1 virus superinfection or iododeoxyuridine treatment.", "content": "Four tetraploid cell lines were derived from the Epstein-Barr virus (EBV)-carrying, nonproducer Burkitt lymphoma line Raji after colcemide treatment. EBV early antigen (EA) was induced by P3HR-1 virus superinfection and by iododeoxyuridine treatment. Inducibility was reduced in all tetraploid lines compared to the near-diploid counterpart. The average number of EBV genome equivalents per tetraploid cell was 60-70, compared to 50 in diploid cells. This contrasts with the EBV genome amplification previously observed in somatic cell hybrids.", "contents": "Polyploidization of Epstein-Barr virus (EBV)-carrying lymphoma lines decreases the inducibility of EBV-determined early antigen following P3HR-1 virus superinfection or iododeoxyuridine treatment. Four tetraploid cell lines were derived from the Epstein-Barr virus (EBV)-carrying, nonproducer Burkitt lymphoma line Raji after colcemide treatment. EBV early antigen (EA) was induced by P3HR-1 virus superinfection and by iododeoxyuridine treatment. Inducibility was reduced in all tetraploid lines compared to the near-diploid counterpart. The average number of EBV genome equivalents per tetraploid cell was 60-70, compared to 50 in diploid cells. This contrasts with the EBV genome amplification previously observed in somatic cell hybrids."}
{"id": "PMID:209005", "title": "Isobaric inert gas supersaturation: observations, theory, and predictions.", "content": "An isobaric inert gas supersaturation model incorporating both diffusion and perfusion properties of biological tissue is presented in a form which allows ready comparison with experimental observations. This model requires only measurement of inert gas flux and blood gas solubility in order to evaluate \"counterdiffusion potential\". Inert gas flux across the skin of Yorkshire piglets anesthetized with pentobarbital was measured for He, Ne, CH4, C2H4, N2O, and SF6. Model predictions based upon these data compare favorably with published reports of isobaric inert gas supersaturation, as well as several previously unpublished observations. The possibility of supersaturation resulting from the use of hydrogen as a breathing gas in a helium environment is also discussed, and extensive animal testing is recommended before potentially dangerous human exposure occurs.", "contents": "Isobaric inert gas supersaturation: observations, theory, and predictions. An isobaric inert gas supersaturation model incorporating both diffusion and perfusion properties of biological tissue is presented in a form which allows ready comparison with experimental observations. This model requires only measurement of inert gas flux and blood gas solubility in order to evaluate \"counterdiffusion potential\". Inert gas flux across the skin of Yorkshire piglets anesthetized with pentobarbital was measured for He, Ne, CH4, C2H4, N2O, and SF6. Model predictions based upon these data compare favorably with published reports of isobaric inert gas supersaturation, as well as several previously unpublished observations. The possibility of supersaturation resulting from the use of hydrogen as a breathing gas in a helium environment is also discussed, and extensive animal testing is recommended before potentially dangerous human exposure occurs."}
{"id": "PMID:209006", "title": "Primary role of respiratory afferents in sustaining breathing rhythm.", "content": "We studied the effects on breathing rhythm of suppressing the major respiratory stimuli (wakefulness, vagal, peripheral and central chemoreceptors) in healthy, unanesthetized dogs. Respiratory frequency (f) was obtained with a pneumotachograph; the state of wakefulness (W) or sleep was determined by EEG and behavioral criteria. During quiet W, f averaged 17 breaths/min and minute volume of ventilation (VI), 8.4 l/min. In slow-wave sleep (SWS), f slowed to 14 breaths/min, and VI decreased to 6.8 l/min. Afferent vagal blockade during SWS slowed f to 4 breaths/min, due primarily to prolongation of expiratory duration (Te) to 13.3 s, and decreased VI to 4.8 l/min. One breath of 100% O2 prolonged Te further to 27.4 s. Central chemoreceptor sensitivity was then reduced by inducting a metabolic alkalosis that combined with SWS, vagal blockade, and hyperoxia prolonged Te to as long as 57 s and reduced f to as low as 1 breath/min. The results demonstrate that afferent respiratory stimuli are essential for sustaining adequate ventilation.", "contents": "Primary role of respiratory afferents in sustaining breathing rhythm. We studied the effects on breathing rhythm of suppressing the major respiratory stimuli (wakefulness, vagal, peripheral and central chemoreceptors) in healthy, unanesthetized dogs. Respiratory frequency (f) was obtained with a pneumotachograph; the state of wakefulness (W) or sleep was determined by EEG and behavioral criteria. During quiet W, f averaged 17 breaths/min and minute volume of ventilation (VI), 8.4 l/min. In slow-wave sleep (SWS), f slowed to 14 breaths/min, and VI decreased to 6.8 l/min. Afferent vagal blockade during SWS slowed f to 4 breaths/min, due primarily to prolongation of expiratory duration (Te) to 13.3 s, and decreased VI to 4.8 l/min. One breath of 100% O2 prolonged Te further to 27.4 s. Central chemoreceptor sensitivity was then reduced by inducting a metabolic alkalosis that combined with SWS, vagal blockade, and hyperoxia prolonged Te to as long as 57 s and reduced f to as low as 1 breath/min. The results demonstrate that afferent respiratory stimuli are essential for sustaining adequate ventilation."}
{"id": "PMID:209007", "title": "Cyclic phosphates of formycin.", "content": "The syntheses of N1- and N2-isopropylformycin (10, 11), formycin 3',5'-cyclic and 2',3'-cyclic phosphate (3,7) and their N-methyl and N-isopropyl derivatives (13, 15, 19, 23) are described. It was observed that substitution at N1 or N2 with a bulky alkyl group or cyclic phosphorylation of the ribose moiety made formycin resistant to adenosine deaminase.", "contents": "Cyclic phosphates of formycin. The syntheses of N1- and N2-isopropylformycin (10, 11), formycin 3',5'-cyclic and 2',3'-cyclic phosphate (3,7) and their N-methyl and N-isopropyl derivatives (13, 15, 19, 23) are described. It was observed that substitution at N1 or N2 with a bulky alkyl group or cyclic phosphorylation of the ribose moiety made formycin resistant to adenosine deaminase."}
{"id": "PMID:209011", "title": "Cell-free synthesis of proteins related to sn-glycerol-3-phosphate transport in Escherichia coli.", "content": "An Escherichia coli periplasmic protein (GlpT) related to sn-glycerol-3-phosphate transport was synthesized in a cell-free system directed by hybrid plasmic ColE1-glpT DNA. The in vitro product cross-reacted with antisera against the purified protein. The ColE1-glpT DNA-directed cell-free system was induced by sn-glycerol-3-phosphate and phosphonomycin and was dependent on cyclic AMP. The in vitro-synthesized protein showed the characteristics of a multimeric protein, as did the purified periplasmic protein. The main proportion of the newly synthesized product had a higher molecular weight than the mature protein found in the periplasm of cells and showed a more positive charge in two-dimensional gel electrophoresis. Thus, a proportion of this protein is presumed to be synthesized in vitro as a precursor. The cell-free system yielded a second protein that is likely to be also coded for by the glpT operon. This protein had a molecular weight of approximately 33,000 in sodium dodecyl sulfate-acrylamide gel electrophoresis and behaved like an intrinsic membrane protein.", "contents": "Cell-free synthesis of proteins related to sn-glycerol-3-phosphate transport in Escherichia coli. An Escherichia coli periplasmic protein (GlpT) related to sn-glycerol-3-phosphate transport was synthesized in a cell-free system directed by hybrid plasmic ColE1-glpT DNA. The in vitro product cross-reacted with antisera against the purified protein. The ColE1-glpT DNA-directed cell-free system was induced by sn-glycerol-3-phosphate and phosphonomycin and was dependent on cyclic AMP. The in vitro-synthesized protein showed the characteristics of a multimeric protein, as did the purified periplasmic protein. The main proportion of the newly synthesized product had a higher molecular weight than the mature protein found in the periplasm of cells and showed a more positive charge in two-dimensional gel electrophoresis. Thus, a proportion of this protein is presumed to be synthesized in vitro as a precursor. The cell-free system yielded a second protein that is likely to be also coded for by the glpT operon. This protein had a molecular weight of approximately 33,000 in sodium dodecyl sulfate-acrylamide gel electrophoresis and behaved like an intrinsic membrane protein."}
{"id": "PMID:209012", "title": "Kinetics of glucose repression of yeast cytochrome c.", "content": "The kinetics of glucose repression of cytochrome c synthesis was measured by a radioimmune assay. When 5 or 10% glucose was added to a derepressed culture, the rate of cytochrome c synthesis was reduced to the repressed level with a half-life of 2 min. The addition of 1 or 0.5% glucose repressed the rate of cytochrome c synthesis to the same level as high glucose concentrations but with a longer half-life of 3 min. Glucose repression had no effect on the stability or function of the cytochrome c protein. Cellular levels of active cytochrome c mRNA during glucose repression were measured by translation of total cellular polyadenylic acid-containing RNA and immunoprecipitation cytochrome c from the translation products. The results of these measurements indicate that glucose represses the rate of cytochrome c synthesis through a reduction in the level of translatable cytochrome c mRNA.", "contents": "Kinetics of glucose repression of yeast cytochrome c. The kinetics of glucose repression of cytochrome c synthesis was measured by a radioimmune assay. When 5 or 10% glucose was added to a derepressed culture, the rate of cytochrome c synthesis was reduced to the repressed level with a half-life of 2 min. The addition of 1 or 0.5% glucose repressed the rate of cytochrome c synthesis to the same level as high glucose concentrations but with a longer half-life of 3 min. Glucose repression had no effect on the stability or function of the cytochrome c protein. Cellular levels of active cytochrome c mRNA during glucose repression were measured by translation of total cellular polyadenylic acid-containing RNA and immunoprecipitation cytochrome c from the translation products. The results of these measurements indicate that glucose represses the rate of cytochrome c synthesis through a reduction in the level of translatable cytochrome c mRNA."}
{"id": "PMID:209013", "title": "Studies on pig serum lipoproteins. V. Optical properties of low density lipoproteins.", "content": "The circular dichroism (CD), optical rotatory dispersion (ORD), and fluorescence emission spectra of two subfractions of pig serum low density lipoproteins (LDL1 and LDL2) were compared. The contribution of the carbohydrate moiety to the CD and ORD spectra was estimated on the basis of data obtained from isolated glycopeptides and the constituent monosaccharides. The carbohydrate moiety had no effect on the conformation of the protein moieties of LDL1 and LDL2 (apoLDL1 and apoLDL2). However, the intensities of the observed extrema in the CD and ORD spectra of the glycopeptides were greater than those expected from the monosaccharide composition. This suggests the existence of secondary structure in the carbohydrate moiety. In contrast to the carbohydrate moiety, the contribution of the lipid moiety to the CD and ORD spectra could not be neglected. When the effect of the lipid moiety was subtrated from the CD and ORD spectra, the spectra due to apoLDL1 and apoLDL2 were quite similar. Delipidation in the presence of sodium dodecyl sulfate (SDS) induced an increase in the content of disordered structure and alpha-helix accompanied by a decrease in the beta-structure. In the presence of SDS, marked quenching occurred in the fluorescence emission spectra with a blue shift of the maximum emission wavelength from 332 to 326 nm. ApoLDL1 and apoLDL2 showed quite similar SDS-induced conformational transitions. The secondary structures of apoLDL1 and apoLDL2 in the native lipoproteins were stable to changes of pH and temperature. However, this stability was lost in the presence of SDS. These results suggest the importance of the lipid moiety in maintaining the native secondary structures of LDL1 and LDL2. From the overall similarity of the optical properties of apoLDL1 and apoLDL2, we conclude that the secondary structures of apoLDL1 and apoLDL2 are identical.", "contents": "Studies on pig serum lipoproteins. V. Optical properties of low density lipoproteins. The circular dichroism (CD), optical rotatory dispersion (ORD), and fluorescence emission spectra of two subfractions of pig serum low density lipoproteins (LDL1 and LDL2) were compared. The contribution of the carbohydrate moiety to the CD and ORD spectra was estimated on the basis of data obtained from isolated glycopeptides and the constituent monosaccharides. The carbohydrate moiety had no effect on the conformation of the protein moieties of LDL1 and LDL2 (apoLDL1 and apoLDL2). However, the intensities of the observed extrema in the CD and ORD spectra of the glycopeptides were greater than those expected from the monosaccharide composition. This suggests the existence of secondary structure in the carbohydrate moiety. In contrast to the carbohydrate moiety, the contribution of the lipid moiety to the CD and ORD spectra could not be neglected. When the effect of the lipid moiety was subtrated from the CD and ORD spectra, the spectra due to apoLDL1 and apoLDL2 were quite similar. Delipidation in the presence of sodium dodecyl sulfate (SDS) induced an increase in the content of disordered structure and alpha-helix accompanied by a decrease in the beta-structure. In the presence of SDS, marked quenching occurred in the fluorescence emission spectra with a blue shift of the maximum emission wavelength from 332 to 326 nm. ApoLDL1 and apoLDL2 showed quite similar SDS-induced conformational transitions. The secondary structures of apoLDL1 and apoLDL2 in the native lipoproteins were stable to changes of pH and temperature. However, this stability was lost in the presence of SDS. These results suggest the importance of the lipid moiety in maintaining the native secondary structures of LDL1 and LDL2. From the overall similarity of the optical properties of apoLDL1 and apoLDL2, we conclude that the secondary structures of apoLDL1 and apoLDL2 are identical."}
{"id": "PMID:209014", "title": "The serine protease from rat liver and hepatoma 8999. Location and role in mitochondrial protein degradation.", "content": "1. Hepatoma 8999 showed extremely high activity of serine protease, but similar activities of other lysosomal proteases to those of normal rat liver. 2. Serine protease from rat liver formed a single immunoprecipitation band against antiserum to purified protease from hepatoma 8999. 3. The serine proteases in rat liver and hepatoma 8999 were restricted to the inner membranes of the mitochondrial fraction. 4. Polyacrylamide gel electrophoresis with sodium dodecylsulfate showed that hepatoma 8999 mitochondria contained less of the slowest moving protein component than rat liver mitochondrial protein. This component was found to be the best substrate for mitochondrial serine protease in both liver and hepatoma 8999. 5. The role of serine protease in mitochondrial protein degradation is discussed on the basis of these results.", "contents": "The serine protease from rat liver and hepatoma 8999. Location and role in mitochondrial protein degradation. 1. Hepatoma 8999 showed extremely high activity of serine protease, but similar activities of other lysosomal proteases to those of normal rat liver. 2. Serine protease from rat liver formed a single immunoprecipitation band against antiserum to purified protease from hepatoma 8999. 3. The serine proteases in rat liver and hepatoma 8999 were restricted to the inner membranes of the mitochondrial fraction. 4. Polyacrylamide gel electrophoresis with sodium dodecylsulfate showed that hepatoma 8999 mitochondria contained less of the slowest moving protein component than rat liver mitochondrial protein. This component was found to be the best substrate for mitochondrial serine protease in both liver and hepatoma 8999. 5. The role of serine protease in mitochondrial protein degradation is discussed on the basis of these results."}
{"id": "PMID:209015", "title": "A new extragenic suppressor of cya mutation. Mutant cyclic AMP receptor protein with an increased affinity for cyclic AMP.", "content": "A strain bearing an extragenic suppressor of cya mutation was isolated as a second-site revertant of an adenylate cyclase deficient strain. The mutant was unable to synthesize cAMP but showed normal fermentation profiles and growth properties on a variety of carbon sources. The site of reversion was mapped in, or near, the structural gene for the cAMP receptor protein. Structural alteration of the protein was directly demonstrated by the following biochemical observations: (i) A 10-fold decrease in the dissociation constant for cAMP, (ii) an acidic shift in the isoelectric point, and (iii) the altered binding properties to lambdah80dlac ps DNA.", "contents": "A new extragenic suppressor of cya mutation. Mutant cyclic AMP receptor protein with an increased affinity for cyclic AMP. A strain bearing an extragenic suppressor of cya mutation was isolated as a second-site revertant of an adenylate cyclase deficient strain. The mutant was unable to synthesize cAMP but showed normal fermentation profiles and growth properties on a variety of carbon sources. The site of reversion was mapped in, or near, the structural gene for the cAMP receptor protein. Structural alteration of the protein was directly demonstrated by the following biochemical observations: (i) A 10-fold decrease in the dissociation constant for cAMP, (ii) an acidic shift in the isoelectric point, and (iii) the altered binding properties to lambdah80dlac ps DNA."}
{"id": "PMID:209016", "title": "Calcium sensitivity of contractile proteins from chicken gizzard muscle.", "content": "Actin, myosin, and \"native\" tropomyosin (NTM) were separately isolated from chicken gizzard muscle and rabbit skeletal muscle. With various combinations of the isolated contractile proteins, Mg-ATPase activity and superprecipitation activity were measured. It was thus found that gizzard myosin and gizzard NTM behaved differently from skeletal myosin and skeletal NTM, whereas gizzard actin functioned in the same wasy as skeletal actin. It was also found that gizzard myosin preparations were often Ca-sensitive, that is, that the two activities of gizzard myosin plus actin without NTM were activated by low concentrations of Ca2+. The Mg-ATPase activity of a Ca-insensitive preparation of gizzard myosin was not activated by actin even in the presence of Ca2+. When Ca-sensitive gizzard myosin was incubated with ATP (and Mg2+) in the presence of Ca2+, a light-chain component of gizzard myosin was phosphorylated. The light-chain phosphorylation also occurred when Ca-insensitive myosin was incubated with gizzard NTM and ATP (plus Mg2+) in the presence of Ca2+. In either case, the light-chain phosphorylation required Ca2+. Phosphorylated gizzard myosin in combination with actin was able to exhibit superprecipitation, and Mg-ATPase of the phosphorylated gizzard myosin was activated by actin; the actin activation and superprecipitation were found to occur even in the absence of Ca2+ and NTM or tropomyosin. The phosphorylated light-chain component was found to be dephosphorylated by a partially purified preparation of gizzard myosin light-chain phosphatase. Gizzard myosin thus dephosphorylated behaved exactly like untreated Ca-insensitive gizzard myosin; in combination with actin, it did not superprecipitate either in the presence of Ca2+ or in its absence, but did superprecipitated in the presence of NTM and Ca2+. Ca-activated hydrolysis of ATP catalyzed by gizzard myosin B proceeded at a reduced rate after removal of Ca2+ (by adding EGTA), whereas that catalyzed by a combination of actin, gizzard myosin, and gizzard NTM proceeded at the same rate even after removal of Ca2+. However, addition of a partially purified preparation of gizzard myosin light-chain phosphatase was found to make the recombined system behave like myosin B. Based on these findings, it appears that myosin light-chain kinase and myosin light-chain phosphatase can function as regulatory proteins for contraction and relaxation, respectively, of gizzard muscle.", "contents": "Calcium sensitivity of contractile proteins from chicken gizzard muscle. Actin, myosin, and \"native\" tropomyosin (NTM) were separately isolated from chicken gizzard muscle and rabbit skeletal muscle. With various combinations of the isolated contractile proteins, Mg-ATPase activity and superprecipitation activity were measured. It was thus found that gizzard myosin and gizzard NTM behaved differently from skeletal myosin and skeletal NTM, whereas gizzard actin functioned in the same wasy as skeletal actin. It was also found that gizzard myosin preparations were often Ca-sensitive, that is, that the two activities of gizzard myosin plus actin without NTM were activated by low concentrations of Ca2+. The Mg-ATPase activity of a Ca-insensitive preparation of gizzard myosin was not activated by actin even in the presence of Ca2+. When Ca-sensitive gizzard myosin was incubated with ATP (and Mg2+) in the presence of Ca2+, a light-chain component of gizzard myosin was phosphorylated. The light-chain phosphorylation also occurred when Ca-insensitive myosin was incubated with gizzard NTM and ATP (plus Mg2+) in the presence of Ca2+. In either case, the light-chain phosphorylation required Ca2+. Phosphorylated gizzard myosin in combination with actin was able to exhibit superprecipitation, and Mg-ATPase of the phosphorylated gizzard myosin was activated by actin; the actin activation and superprecipitation were found to occur even in the absence of Ca2+ and NTM or tropomyosin. The phosphorylated light-chain component was found to be dephosphorylated by a partially purified preparation of gizzard myosin light-chain phosphatase. Gizzard myosin thus dephosphorylated behaved exactly like untreated Ca-insensitive gizzard myosin; in combination with actin, it did not superprecipitate either in the presence of Ca2+ or in its absence, but did superprecipitated in the presence of NTM and Ca2+. Ca-activated hydrolysis of ATP catalyzed by gizzard myosin B proceeded at a reduced rate after removal of Ca2+ (by adding EGTA), whereas that catalyzed by a combination of actin, gizzard myosin, and gizzard NTM proceeded at the same rate even after removal of Ca2+. However, addition of a partially purified preparation of gizzard myosin light-chain phosphatase was found to make the recombined system behave like myosin B. Based on these findings, it appears that myosin light-chain kinase and myosin light-chain phosphatase can function as regulatory proteins for contraction and relaxation, respectively, of gizzard muscle."}
{"id": "PMID:209017", "title": "Studies on pig serum lipoproteins. VI. Surface charge of very low density lipoprotein.", "content": "The surface electric charge of pig serum very low density lipoprotein (VLDL) is described. By isoelectric focusing VLDL was separated into at least 3 fractions having different isoelectric points and polypeptide distributions. The ultracentrifugal and electron microscopic results indicate that the VLDL was not drastically denatured by Ampholine.", "contents": "Studies on pig serum lipoproteins. VI. Surface charge of very low density lipoprotein. The surface electric charge of pig serum very low density lipoprotein (VLDL) is described. By isoelectric focusing VLDL was separated into at least 3 fractions having different isoelectric points and polypeptide distributions. The ultracentrifugal and electron microscopic results indicate that the VLDL was not drastically denatured by Ampholine."}
{"id": "PMID:209018", "title": "Muscarinic cholinergic receptor modulation of beta-adrenergic receptor affinity for catecholamines.", "content": "The effects of the muscarinic cholinergic agonist methacholine on affinity of beta-adrenergic receptors for isoproterenol and on isoproterenol-induced stimulation of adenylate cyclase activity were assessed in canine myocardium. GTP and guanyl-5'-yl imidoiphosphate both decreased the affinity of beta-adrenergic receptors for isoproterenol without altering the affinity of these receptors for propranolol. Methacholine (10 nM to 10 micronM) antagonized the guanine nucleotide-induced reduction in beta-adrenergic receptor affinity for isoproterenol. This effect of methacholine was reversed by atropine. The choline ester had no effect on the affinity of beta-adrenergic receptors for isoproterenol in the absence of guanine nucleotides. Likewise, methacholine had no effect on the affinity of beta-adrenergic receptors for propranolol, either in the presence or absence of guanine nucleotides. Methacholine also attenuated GTP-induced activation of adenylate cyclase or isoproterenol-induced activation of the enzyme in the presence of GTP. The effects of methacholine on myocardial adenylate cyclase activity were apparent only in the presence of GTP. These effects were also reversed by atropine. The choline ester had no effect on adenylate cyclase activity in the presence of guanyl-5'-yl imidodiphosphate or NaF. The results of the present study suggest that muscarinic cholinergic agonists can regulate both beta-adrenergic receptors and adenylate cyclase by modulating the effects of GTP.", "contents": "Muscarinic cholinergic receptor modulation of beta-adrenergic receptor affinity for catecholamines. The effects of the muscarinic cholinergic agonist methacholine on affinity of beta-adrenergic receptors for isoproterenol and on isoproterenol-induced stimulation of adenylate cyclase activity were assessed in canine myocardium. GTP and guanyl-5'-yl imidoiphosphate both decreased the affinity of beta-adrenergic receptors for isoproterenol without altering the affinity of these receptors for propranolol. Methacholine (10 nM to 10 micronM) antagonized the guanine nucleotide-induced reduction in beta-adrenergic receptor affinity for isoproterenol. This effect of methacholine was reversed by atropine. The choline ester had no effect on the affinity of beta-adrenergic receptors for isoproterenol in the absence of guanine nucleotides. Likewise, methacholine had no effect on the affinity of beta-adrenergic receptors for propranolol, either in the presence or absence of guanine nucleotides. Methacholine also attenuated GTP-induced activation of adenylate cyclase or isoproterenol-induced activation of the enzyme in the presence of GTP. The effects of methacholine on myocardial adenylate cyclase activity were apparent only in the presence of GTP. These effects were also reversed by atropine. The choline ester had no effect on adenylate cyclase activity in the presence of guanyl-5'-yl imidodiphosphate or NaF. The results of the present study suggest that muscarinic cholinergic agonists can regulate both beta-adrenergic receptors and adenylate cyclase by modulating the effects of GTP."}
{"id": "PMID:209020", "title": "Gradients of O2 concentration in hepatocytes.", "content": "1. Cytochrome P/450-dependent mixed function oxidations of hexobarbital, phenyramidol, and alprenolol in intact hepatocytes were examined at different steady state oxygen concentrations. Apparent Kmo2 values were determined to be 6.4 +/- 1.7, 3.6 +/- 0.6, and 9.8 +/- 1.2 micronM, respectively. 2. Apparent Kmo2 values for metabolism of hexobarbital and alprenolol by liver microsomes were 4.3 +/- 0.4 and 8.7 +/- 0.7 micronM, similar to the corresponding values for whole cells. Therefore, no detectable gradient of O2 concentration exists between extracellular space and endoplasmic reticulum of hepatocytes at these oxygen concentrations. 3. Steady state concentrations of ATP, ADP, AMP, lactate, and pyruvate at different steady state oxygen concentrations were used as indicators of mitochondrial oxygen dependence in intact hepatocytes. Half-maximal changes occurred at [O2] = 12.6 micronM for cytoplasmic [NAD+]/[NADH] (estimated from [lactate]/[pyruvate]), at 7.0 micronM for [ATP]/[ADP], and at 2.8 micronM for adenylate energy charge. The apparent cellular respiratory Kmo2 was 1.90 +/- 0.18 micronM. 4. Comparison of values for oxygen dependence of mitochondrial functions in isolated hepatocytes with published values for isolated mitochondria suggests that a substantial intracellular oxygen gradient exists between the outer cellular membrane and the mitochondrial inner membrane at po2 values below the critical O2 tensions.", "contents": "Gradients of O2 concentration in hepatocytes. 1. Cytochrome P/450-dependent mixed function oxidations of hexobarbital, phenyramidol, and alprenolol in intact hepatocytes were examined at different steady state oxygen concentrations. Apparent Kmo2 values were determined to be 6.4 +/- 1.7, 3.6 +/- 0.6, and 9.8 +/- 1.2 micronM, respectively. 2. Apparent Kmo2 values for metabolism of hexobarbital and alprenolol by liver microsomes were 4.3 +/- 0.4 and 8.7 +/- 0.7 micronM, similar to the corresponding values for whole cells. Therefore, no detectable gradient of O2 concentration exists between extracellular space and endoplasmic reticulum of hepatocytes at these oxygen concentrations. 3. Steady state concentrations of ATP, ADP, AMP, lactate, and pyruvate at different steady state oxygen concentrations were used as indicators of mitochondrial oxygen dependence in intact hepatocytes. Half-maximal changes occurred at [O2] = 12.6 micronM for cytoplasmic [NAD+]/[NADH] (estimated from [lactate]/[pyruvate]), at 7.0 micronM for [ATP]/[ADP], and at 2.8 micronM for adenylate energy charge. The apparent cellular respiratory Kmo2 was 1.90 +/- 0.18 micronM. 4. Comparison of values for oxygen dependence of mitochondrial functions in isolated hepatocytes with published values for isolated mitochondria suggests that a substantial intracellular oxygen gradient exists between the outer cellular membrane and the mitochondrial inner membrane at po2 values below the critical O2 tensions."}
{"id": "PMID:209022", "title": "Structural determination and stereospecificity of the choleragen-catalyzed reaction of NAD+ with guanidines.", "content": "The products of the choleragen-catalyzed reaction of NAD+ with guanidine HCl or L-arginine have been isolated by high performance liquid chromatography. Analysis of 1H NMR spectra obtained at 360 MHz establishes the structure of the isolated products to be adenosine diphosphoribosyl guanidiniums present as 1:1 mixtures of alpha and beta anomeric forms. Direct observation of the choleragen-catalyzed reaction of NAD+ with L-arginine by 1H NMR spectroscopy establishes that choleragen synthesizes an alpha anomeric linkage that is subject to subsequent anomerization. The stereospecificity of the reaction provides further evidence that choleragen behaves as an enzyme and may be related mechanistically to other ADP-ribosyltransferases.", "contents": "Structural determination and stereospecificity of the choleragen-catalyzed reaction of NAD+ with guanidines. The products of the choleragen-catalyzed reaction of NAD+ with guanidine HCl or L-arginine have been isolated by high performance liquid chromatography. Analysis of 1H NMR spectra obtained at 360 MHz establishes the structure of the isolated products to be adenosine diphosphoribosyl guanidiniums present as 1:1 mixtures of alpha and beta anomeric forms. Direct observation of the choleragen-catalyzed reaction of NAD+ with L-arginine by 1H NMR spectroscopy establishes that choleragen synthesizes an alpha anomeric linkage that is subject to subsequent anomerization. The stereospecificity of the reaction provides further evidence that choleragen behaves as an enzyme and may be related mechanistically to other ADP-ribosyltransferases."}
{"id": "PMID:209023", "title": "Isolation of subfractions of human very low density lipoproteins by zonal ultracentrifugation.", "content": "Very low density lipoproteins (VLDL) have been isolated and subfractionated on the basis of their differing flotation rates. The procedure consists of a single 45-min zonal ultracentrifugation step using a linear density gradient of d = 1.00 to 1.15 g/ml. Appropriate fractions of the zonal rotor effluent containing the entire VLDL spectrum were characterized by analytical ultracentrifugation, gel filtration chromatography, and complete chemical analysis. Flotation rates of VLDL subspecies from hypertriglyceridemic and normolipemic plasmas correlated directly with their Stokes radii and triglyceride content and inversely with their proportion of cholesterol, cholesteryl esters, phospholipids, and total protein. There was also an inverse correlation of flotation rate with the fraction of tetramethylurea-insoluble protein. This procedure provides a reliable methodology for a rapid isolation of VLDL subfractions and the accurate determination of their flotation rates.", "contents": "Isolation of subfractions of human very low density lipoproteins by zonal ultracentrifugation. Very low density lipoproteins (VLDL) have been isolated and subfractionated on the basis of their differing flotation rates. The procedure consists of a single 45-min zonal ultracentrifugation step using a linear density gradient of d = 1.00 to 1.15 g/ml. Appropriate fractions of the zonal rotor effluent containing the entire VLDL spectrum were characterized by analytical ultracentrifugation, gel filtration chromatography, and complete chemical analysis. Flotation rates of VLDL subspecies from hypertriglyceridemic and normolipemic plasmas correlated directly with their Stokes radii and triglyceride content and inversely with their proportion of cholesterol, cholesteryl esters, phospholipids, and total protein. There was also an inverse correlation of flotation rate with the fraction of tetramethylurea-insoluble protein. This procedure provides a reliable methodology for a rapid isolation of VLDL subfractions and the accurate determination of their flotation rates."}
{"id": "PMID:209024", "title": "The role of phosphatidylglycerol in the activation of CTP:phosphocholine cytidylyltransferase from rat lung.", "content": "The reaction catalyzed by CTP:phosphocholine cytidylyltransferase in the reverse direction, i.e. the formation of CTP and phosphocholine from CDP-choline and pyrophosphate, is slightly faster than the reaction in the forward direction. The reverse reaction is optimal at 2 mM pyrophosphate and 6 mM Mg2+, in both fetal and adult preparations. The apparent substrate Km values for phosphocholine, CDP-choline, and pyrophosphate are similar in the fetal and adult forms of the enzyme. The enzyme activity is separated into two forms by gel filtration. The enzyme from adult lung exists as a high molecular weight species, ranging in size from 5 X 10(6) to 50 X 10(6). The enzyme from fetal lung exists as a 190,000 molecular weight species and is totally dependent upon added anionic phospholipid for activity in both the forward and reverse direction. The addition of phosphatidylglycerol gives maximal activity, while phosphatidylinositol or cardiolipin produce about 60 to 70% of the maximal activity. Enzyme activation is accompanied by an aggregation of the enzyme. A sonicated preparation of phosphatidylglycerol is a more efficient activator than a preparation mixed on a Vortex mixer (KA = 30 micronM) and also converts a larger proportion of enzyme from fetal lung into a high molecular weight species. The enzyme from adult lung can be dissociated into a form in fetal lung. The dissociated species can be converted back to a high molecular weight form in the presence of phosphatidylglycerol.", "contents": "The role of phosphatidylglycerol in the activation of CTP:phosphocholine cytidylyltransferase from rat lung. The reaction catalyzed by CTP:phosphocholine cytidylyltransferase in the reverse direction, i.e. the formation of CTP and phosphocholine from CDP-choline and pyrophosphate, is slightly faster than the reaction in the forward direction. The reverse reaction is optimal at 2 mM pyrophosphate and 6 mM Mg2+, in both fetal and adult preparations. The apparent substrate Km values for phosphocholine, CDP-choline, and pyrophosphate are similar in the fetal and adult forms of the enzyme. The enzyme activity is separated into two forms by gel filtration. The enzyme from adult lung exists as a high molecular weight species, ranging in size from 5 X 10(6) to 50 X 10(6). The enzyme from fetal lung exists as a 190,000 molecular weight species and is totally dependent upon added anionic phospholipid for activity in both the forward and reverse direction. The addition of phosphatidylglycerol gives maximal activity, while phosphatidylinositol or cardiolipin produce about 60 to 70% of the maximal activity. Enzyme activation is accompanied by an aggregation of the enzyme. A sonicated preparation of phosphatidylglycerol is a more efficient activator than a preparation mixed on a Vortex mixer (KA = 30 micronM) and also converts a larger proportion of enzyme from fetal lung into a high molecular weight species. The enzyme from adult lung can be dissociated into a form in fetal lung. The dissociated species can be converted back to a high molecular weight form in the presence of phosphatidylglycerol."}
{"id": "PMID:209026", "title": "(+/-)-[3H]Epinephrine and (-)[3H]dihydroalprenolol binding to beta1- and beta2-noradrenergic receptors in brain, heart, and lung membranes.", "content": "(+/-)-[3H]Epinephrine binds to beta-receptors in calf cerebellar and rat lung membranes in the presence of 1.0 mM pyrocatechol and 1.0 microM phentolamine, with dissociation constants at 4 degrees C of 11 nM and 24 nM, respectively. (+/-)-[3H]Epinephrine associates to equilibrium within 20 min in both tissues, and over 50% of the binding is rapidly dissociable. Inhibition of binding by agonists and antagonists is highly stereoselective, and the structure-activity relationships of adrenergic agents in inhibiting (+/-)-[3H]epinephrine binding suggest an interaction with beta2 type noradrenergic receptors. (-)-Isoproterenol has an apparent Ki of 2 nM, (-)-epinephrine is 1.5 to 3 times weaker, and (-)-norepinephrine is 30 to 60 times weaker. Salbutamol and terbutaline, selective beta2-agonists, are potent inhibitors of binding, as are several nonspecific antagonists. Properties of the sites labeled by (+/-)-[3H]epinephrine in calf cerebellum and rat lung are closely similar. (-)-[3H]Dihydroalprenolol binding in calf cerebellum and rat lung also shows beta2 characteristics. Antagonists have similar potencies in inhibiting (-)-[3H]dihydroalprenolol and (+/-)-[3H]epinephrine binding in both tissues, but agonists are in general more potent inhibitors of (+/-)-[3H]epinephrine. Sodium and lithium selectively lower the affinity of (+/-)-[3H]epinephrine at its binding sites and the affinities of agonists, but not antagonists, at the (-)-[3H]dihydroalprenolol site. Specific (+/-)-[3H]epinephrine binding was not detectable in calf cortex and rat heart, where (-)-[3H]dihydroalprenolol binding suggests a beta1-receptor. A physiological significance of (+/-)-[3H]epinephrine binding is suggested by the strong correlation for agonists and antagonists between affinities in inhibiting binding, and in stimulating or inhibiting a beta-receptor-coupled adenylate cyclase in frog erythrocytes.", "contents": "(+/-)-[3H]Epinephrine and (-)[3H]dihydroalprenolol binding to beta1- and beta2-noradrenergic receptors in brain, heart, and lung membranes. (+/-)-[3H]Epinephrine binds to beta-receptors in calf cerebellar and rat lung membranes in the presence of 1.0 mM pyrocatechol and 1.0 microM phentolamine, with dissociation constants at 4 degrees C of 11 nM and 24 nM, respectively. (+/-)-[3H]Epinephrine associates to equilibrium within 20 min in both tissues, and over 50% of the binding is rapidly dissociable. Inhibition of binding by agonists and antagonists is highly stereoselective, and the structure-activity relationships of adrenergic agents in inhibiting (+/-)-[3H]epinephrine binding suggest an interaction with beta2 type noradrenergic receptors. (-)-Isoproterenol has an apparent Ki of 2 nM, (-)-epinephrine is 1.5 to 3 times weaker, and (-)-norepinephrine is 30 to 60 times weaker. Salbutamol and terbutaline, selective beta2-agonists, are potent inhibitors of binding, as are several nonspecific antagonists. Properties of the sites labeled by (+/-)-[3H]epinephrine in calf cerebellum and rat lung are closely similar. (-)-[3H]Dihydroalprenolol binding in calf cerebellum and rat lung also shows beta2 characteristics. Antagonists have similar potencies in inhibiting (-)-[3H]dihydroalprenolol and (+/-)-[3H]epinephrine binding in both tissues, but agonists are in general more potent inhibitors of (+/-)-[3H]epinephrine. Sodium and lithium selectively lower the affinity of (+/-)-[3H]epinephrine at its binding sites and the affinities of agonists, but not antagonists, at the (-)-[3H]dihydroalprenolol site. Specific (+/-)-[3H]epinephrine binding was not detectable in calf cortex and rat heart, where (-)-[3H]dihydroalprenolol binding suggests a beta1-receptor. A physiological significance of (+/-)-[3H]epinephrine binding is suggested by the strong correlation for agonists and antagonists between affinities in inhibiting binding, and in stimulating or inhibiting a beta-receptor-coupled adenylate cyclase in frog erythrocytes."}
{"id": "PMID:209027", "title": "Altered metabolism of heparan sulfate in simian virus 40 transformed cloned mouse cells.", "content": "Glycoconjugates have been analyzed from a family of closely related mouse cells: a parent clone and three daughter subclones, two of which expressed the simian virus 40 (SV40) T-antigen. The experimental procedure involved the simultaneous comparison by DEAE-cellulose chromatography of papain-digested macromolecules from the parent, labeled with [3H]glucosamine, and one of the daughter subclones, labeled with [14C]-glucosamine. Three cultures compartments (the medium, the cell surface trypsinate, and the cells) from the paired cell lines were combined at the earliest time during the harvesting of the cells. Heparan sulfate on the surface of cells and secreted into the medium from T-antigen-positive subclones was eluted at lower salt concentrations from the anion exchange column than that from the parent clone. In the viable trypsinized cells a marked reduction of heparan sulfate was detected in the T-antigen-positive subclones. These changes were highly reproducible, were observed during both logarithmic and stationary phase of growth, and neither change was observed in the T-antigen-negative sister subclone. The elution point of heparan sulfate from Sepharose 6B was unaltered. Ratios of 35S to 3H for heparan sulfate obtained from cells doubly labeled with [35S]sulfate and [3H]glucosamine were lower in the T-antigen-positive subclones. Similar changes for the 35S to 3H ratio of chondroitin sulfate were associated with only small alterations in elution from anion exchange columns. Kinetic experiments suggested a reduced rate of incorporation of [35S]sulfate with no change in turnover rate. A substantial portion of the labeled heparan sulfate was associated with the cell surface; in contrast most of the hyaluronic acid and a large proportion of the chondroitin sulfate was apparently secreted. Quantitative changes in hyaluronic acid labeling did not correlate with expression of T-antigen. Glycosaminoglycans left on the dish after detaching cells with ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid were nearly completely released by subsequent trypsinization. Cell detachment by trypsinization left an insignificant amount of labeled glycosaminoglycan on the dish surface. The alterations in heparan sulfate metabolism correlated with the expression of T-antigen and with the cells' ability to grow to high densities in monolayer culture, but not with growth in suspension in viscous medium. Tumorigenicity of the subclones was essentially the same as that of the parent clone.", "contents": "Altered metabolism of heparan sulfate in simian virus 40 transformed cloned mouse cells. Glycoconjugates have been analyzed from a family of closely related mouse cells: a parent clone and three daughter subclones, two of which expressed the simian virus 40 (SV40) T-antigen. The experimental procedure involved the simultaneous comparison by DEAE-cellulose chromatography of papain-digested macromolecules from the parent, labeled with [3H]glucosamine, and one of the daughter subclones, labeled with [14C]-glucosamine. Three cultures compartments (the medium, the cell surface trypsinate, and the cells) from the paired cell lines were combined at the earliest time during the harvesting of the cells. Heparan sulfate on the surface of cells and secreted into the medium from T-antigen-positive subclones was eluted at lower salt concentrations from the anion exchange column than that from the parent clone. In the viable trypsinized cells a marked reduction of heparan sulfate was detected in the T-antigen-positive subclones. These changes were highly reproducible, were observed during both logarithmic and stationary phase of growth, and neither change was observed in the T-antigen-negative sister subclone. The elution point of heparan sulfate from Sepharose 6B was unaltered. Ratios of 35S to 3H for heparan sulfate obtained from cells doubly labeled with [35S]sulfate and [3H]glucosamine were lower in the T-antigen-positive subclones. Similar changes for the 35S to 3H ratio of chondroitin sulfate were associated with only small alterations in elution from anion exchange columns. Kinetic experiments suggested a reduced rate of incorporation of [35S]sulfate with no change in turnover rate. A substantial portion of the labeled heparan sulfate was associated with the cell surface; in contrast most of the hyaluronic acid and a large proportion of the chondroitin sulfate was apparently secreted. Quantitative changes in hyaluronic acid labeling did not correlate with expression of T-antigen. Glycosaminoglycans left on the dish after detaching cells with ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid were nearly completely released by subsequent trypsinization. Cell detachment by trypsinization left an insignificant amount of labeled glycosaminoglycan on the dish surface. The alterations in heparan sulfate metabolism correlated with the expression of T-antigen and with the cells' ability to grow to high densities in monolayer culture, but not with growth in suspension in viscous medium. Tumorigenicity of the subclones was essentially the same as that of the parent clone."}
{"id": "PMID:209031", "title": "Relationships between dephosphorylation and D to I conversion of rabbit skeletal muscle glycogen synthase.", "content": "The relationship between dephosphorylation and D to I conversion of skeletal muscle glycogen synthase by synthase phosphatase was investigated using synthase preparations containing 1 to 3 mol of 32P/mol of subunit (90,000 g). Dephosphorylation was analyzed in terms of 32P release from the trypsin-sensitive and trypsin-insensitive phosphorylation regions of synthase. With synthase containing 1 to 2 mol of 32P/90,000 g, dephosphorylation of the trypsin-insensitive region correlated closely with D to I conversion and was more rapid than dephosphorylation of the trypsin-sensitive region. Synthase containing 3 mol of 32P/90,000 g was a relatively poor substrate for the phosphatase since dephosphorylation of both regions, as well as D to I conversion, was slow. With this species of synthase, glucose-6-P (0.1 mM) increased the rates of D to I conversion and dephosphorylation of trypsin-insensitive region. It is concluded that dephosphorylation of the trypsin-insensitive region is responsible for the conversion of synthase D to I.", "contents": "Relationships between dephosphorylation and D to I conversion of rabbit skeletal muscle glycogen synthase. The relationship between dephosphorylation and D to I conversion of skeletal muscle glycogen synthase by synthase phosphatase was investigated using synthase preparations containing 1 to 3 mol of 32P/mol of subunit (90,000 g). Dephosphorylation was analyzed in terms of 32P release from the trypsin-sensitive and trypsin-insensitive phosphorylation regions of synthase. With synthase containing 1 to 2 mol of 32P/90,000 g, dephosphorylation of the trypsin-insensitive region correlated closely with D to I conversion and was more rapid than dephosphorylation of the trypsin-sensitive region. Synthase containing 3 mol of 32P/90,000 g was a relatively poor substrate for the phosphatase since dephosphorylation of both regions, as well as D to I conversion, was slow. With this species of synthase, glucose-6-P (0.1 mM) increased the rates of D to I conversion and dephosphorylation of trypsin-insensitive region. It is concluded that dephosphorylation of the trypsin-insensitive region is responsible for the conversion of synthase D to I."}
{"id": "PMID:209032", "title": "Phosphorylation of NAD-dependent glutamate dehydrogenase from yeast.", "content": "The NAD-dependent glutamate dehydrogenase from Candida utilis was isolated from 32P-labeled cells following enzyme inactivation promoted by glutamate starvation and found to exist in a phosphorylated form. Analysis of purified, fully active NAD-dependent glutamate dehydrogenase (a form) and inactive NAD-dependent glutamate dehydrogenase (b form) for alkalilabile phosphate revealed that the a form contained 0.09 +/- 0.06 mol of phosphate/mol of enzyme subunit and b form 1.25 +/- 0.06 mol of phosphate/mol of enzyme subunit. Phosphorylation caused a 10-fold reduction in enzyme specific activity. Dephosphorylation (release of 32P) and enzyme reactivation occurred on incubation with cell-free yeast extracts, indicating the presence of a phosphoprotein phosphatase in such preparations.", "contents": "Phosphorylation of NAD-dependent glutamate dehydrogenase from yeast. The NAD-dependent glutamate dehydrogenase from Candida utilis was isolated from 32P-labeled cells following enzyme inactivation promoted by glutamate starvation and found to exist in a phosphorylated form. Analysis of purified, fully active NAD-dependent glutamate dehydrogenase (a form) and inactive NAD-dependent glutamate dehydrogenase (b form) for alkalilabile phosphate revealed that the a form contained 0.09 +/- 0.06 mol of phosphate/mol of enzyme subunit and b form 1.25 +/- 0.06 mol of phosphate/mol of enzyme subunit. Phosphorylation caused a 10-fold reduction in enzyme specific activity. Dephosphorylation (release of 32P) and enzyme reactivation occurred on incubation with cell-free yeast extracts, indicating the presence of a phosphoprotein phosphatase in such preparations."}
{"id": "PMID:209034", "title": "Protein is linked to the 5' end of poliovirus RNA by a phosphodiester linkage to tyrosine.", "content": "Purification and partial characterization of the poliovirus RNA-linked protein (VPg) are described. VPg has been freed from the RNA by ribonuclease digestion and phenol extraction. Gel filtration chromatography of VPg-pUp (labeled with 32P) in 0.5% sodium dodecyl sulfate or 6 M guanidine HCl indicates that it has a molecular weight of about 12,000. VPg is bound to the 5' end of poliovirion RNA by a phosphodiester bond between a tyrosine residue in the VPg molecule and the 5'-terminal uridine. After acid hydrolysis of [3H]tyrosine-labeled VPg-pU, free tyrosine can be released by venom phosphodiesterase. Acid hydrolysis of VPg-p labeled with either 32P or [3H] tyrosine yields tyrosine-phosphate. There appears to be only 1 tyrosine residue per VPg molecule.", "contents": "Protein is linked to the 5' end of poliovirus RNA by a phosphodiester linkage to tyrosine. Purification and partial characterization of the poliovirus RNA-linked protein (VPg) are described. VPg has been freed from the RNA by ribonuclease digestion and phenol extraction. Gel filtration chromatography of VPg-pUp (labeled with 32P) in 0.5% sodium dodecyl sulfate or 6 M guanidine HCl indicates that it has a molecular weight of about 12,000. VPg is bound to the 5' end of poliovirion RNA by a phosphodiester bond between a tyrosine residue in the VPg molecule and the 5'-terminal uridine. After acid hydrolysis of [3H]tyrosine-labeled VPg-pU, free tyrosine can be released by venom phosphodiesterase. Acid hydrolysis of VPg-p labeled with either 32P or [3H] tyrosine yields tyrosine-phosphate. There appears to be only 1 tyrosine residue per VPg molecule."}
{"id": "PMID:209035", "title": "alpha-adrenergic receptor in rat heart. Effects of thyroidectomy.", "content": "The effects of thyroid status on alpha-adrenergic receptors in the rat myocardium were investigated. The potent antagonist [3H]dihydroergokryptine was used to identify alpha-adrenergic receptors in rat heart particulate and sarcolemmal fractions. Administration of triiodothyronine to thyroidectomized rats decreased specific binding to alpha-adrenergic receptors in heart particulate and sarcolemmal fractions by 41% and 45%, respectively. Scatchard analysis revealed that the cardiac sarcolemmal fraction from thyroidectomized rats contained 29.3 fmol/mg of protein, as compared with 17.0 fmol/mg of protein found in the heart preparation of thyroidectomized rats treated with triiodothyronine. The equilibrium dissociation constants for the interaction of receptors with dihydroergokryptine were similar (about 1.5 nM) in the heart sarcolemmal fractions derived from these two groups of rats. The results of this study demonstrate that thyroid hormone can regulate the number of cardiac alpha-adrenergic receptors. In addition, there appears to be a reciprocal relationship between alpha-adrenergic and beta-adrenergic receptors in the rat myocardium.", "contents": "alpha-adrenergic receptor in rat heart. Effects of thyroidectomy. The effects of thyroid status on alpha-adrenergic receptors in the rat myocardium were investigated. The potent antagonist [3H]dihydroergokryptine was used to identify alpha-adrenergic receptors in rat heart particulate and sarcolemmal fractions. Administration of triiodothyronine to thyroidectomized rats decreased specific binding to alpha-adrenergic receptors in heart particulate and sarcolemmal fractions by 41% and 45%, respectively. Scatchard analysis revealed that the cardiac sarcolemmal fraction from thyroidectomized rats contained 29.3 fmol/mg of protein, as compared with 17.0 fmol/mg of protein found in the heart preparation of thyroidectomized rats treated with triiodothyronine. The equilibrium dissociation constants for the interaction of receptors with dihydroergokryptine were similar (about 1.5 nM) in the heart sarcolemmal fractions derived from these two groups of rats. The results of this study demonstrate that thyroid hormone can regulate the number of cardiac alpha-adrenergic receptors. In addition, there appears to be a reciprocal relationship between alpha-adrenergic and beta-adrenergic receptors in the rat myocardium."}
{"id": "PMID:209036", "title": "Effect of tunicamycin on the secretion of serum proteins by primary cultures of rat and chick hepatocytes. Studies on transferrin, very low density lipoprotein, and serum albumin.", "content": "Using rat or chick hepatocyte monolayers, we have studied the effect of tunicamycin, a specific inhibitor of protein glycosylation, on the synthesis and secretion of serum proteins. Tunicamycin inhibited glucosamine incorporation into rat liver transferrin and the apoprotein B chain of chick liver very low density lipoprotein (VLDL) by 75 to 90%. In contrasts, amino acid incorporation into these two glycoproteins, as well as into the normally unglycosylated proteins, rat serum albumin and apoprotein A of chick liver VLDL, was decreased by only 10 to 25% in the presence of the antibiotic. Despite the inhibitory effect of tunicamycin on glycosylation, secretion of all four proteins was virtually unimpaired. Thus, the carbohydrate moieties of rat liver transferrin or apoprotein B of chick liver VLDL do not appear to play an essential role in the secretion process.", "contents": "Effect of tunicamycin on the secretion of serum proteins by primary cultures of rat and chick hepatocytes. Studies on transferrin, very low density lipoprotein, and serum albumin. Using rat or chick hepatocyte monolayers, we have studied the effect of tunicamycin, a specific inhibitor of protein glycosylation, on the synthesis and secretion of serum proteins. Tunicamycin inhibited glucosamine incorporation into rat liver transferrin and the apoprotein B chain of chick liver very low density lipoprotein (VLDL) by 75 to 90%. In contrasts, amino acid incorporation into these two glycoproteins, as well as into the normally unglycosylated proteins, rat serum albumin and apoprotein A of chick liver VLDL, was decreased by only 10 to 25% in the presence of the antibiotic. Despite the inhibitory effect of tunicamycin on glycosylation, secretion of all four proteins was virtually unimpaired. Thus, the carbohydrate moieties of rat liver transferrin or apoprotein B of chick liver VLDL do not appear to play an essential role in the secretion process."}
{"id": "PMID:209041", "title": "Regulation of adenosine 3':5'-monophosphate efflux from animal cells.", "content": "Cyclic AMP efflux was measured following hormonal stimulation of adenylate cyclase in a variety of animal cells including C-6 rat glioma cells, WI-38 human fibroblasts, and avian erythrocytes. Using a variety inhibitors of mitochondrial function and glycolysis, a correlation was noted between cellular ATP levels and the rate of cyclic AMP efflux in all cells examined. A relationship between the efflux rate and the magnitude of the membrane potential was not observed. Pharmacological agents which inhibited cyclic AMP egress in these cells without reducing ATP levels included several prostaglandins (A greater than B greater than E greater than F) and probenecid. The characteristics of the cyclic AMP efflux system resemble those of the organic anion transport system.", "contents": "Regulation of adenosine 3':5'-monophosphate efflux from animal cells. Cyclic AMP efflux was measured following hormonal stimulation of adenylate cyclase in a variety of animal cells including C-6 rat glioma cells, WI-38 human fibroblasts, and avian erythrocytes. Using a variety inhibitors of mitochondrial function and glycolysis, a correlation was noted between cellular ATP levels and the rate of cyclic AMP efflux in all cells examined. A relationship between the efflux rate and the magnitude of the membrane potential was not observed. Pharmacological agents which inhibited cyclic AMP egress in these cells without reducing ATP levels included several prostaglandins (A greater than B greater than E greater than F) and probenecid. The characteristics of the cyclic AMP efflux system resemble those of the organic anion transport system."}
{"id": "PMID:209044", "title": "Chinese hamster lung cell polysomes direct the synthesis of a single molecular weight species of procollagen alpha chains.", "content": "Polysomes prepared from cultured Chinese hamster lung cells direct the synthesis of procollagen alpha chains in an heterologous cell-free system containing the postribosomal supernatant fraction prepared from wheat germ. Total protein synthesis requires both subcellular components and an exogenous energy source, and is inhibited by the antibiotics puromycin and aurin tricarboxylic acid. The ratio of collagenase-digestible to nondigestible material produced depends upon the wheat germ and not the polysome level in the reaction. Under optimal conditions, a significant fraction of the total product migrates on denaturing sodium dodecyl sulfate-polyacrylamide gels as a single molecular weight collagenase-digestible species corresponding in size to the procollagen alpha chain (Mr approximately equal to 170,000). Approximately one-third of this high molecular weight material represents products whose synthesis results from cell-free mRNA initiation, and no distinct product larger than the 170,000-dalton material is observed. These studies confirm the initial observation that collagen represents one of the major gene products of Chinese hamster lung cells and demonstrate the usefulness of this cell line for the study of mammalian collagen biosynthesis.", "contents": "Chinese hamster lung cell polysomes direct the synthesis of a single molecular weight species of procollagen alpha chains. Polysomes prepared from cultured Chinese hamster lung cells direct the synthesis of procollagen alpha chains in an heterologous cell-free system containing the postribosomal supernatant fraction prepared from wheat germ. Total protein synthesis requires both subcellular components and an exogenous energy source, and is inhibited by the antibiotics puromycin and aurin tricarboxylic acid. The ratio of collagenase-digestible to nondigestible material produced depends upon the wheat germ and not the polysome level in the reaction. Under optimal conditions, a significant fraction of the total product migrates on denaturing sodium dodecyl sulfate-polyacrylamide gels as a single molecular weight collagenase-digestible species corresponding in size to the procollagen alpha chain (Mr approximately equal to 170,000). Approximately one-third of this high molecular weight material represents products whose synthesis results from cell-free mRNA initiation, and no distinct product larger than the 170,000-dalton material is observed. These studies confirm the initial observation that collagen represents one of the major gene products of Chinese hamster lung cells and demonstrate the usefulness of this cell line for the study of mammalian collagen biosynthesis."}
{"id": "PMID:209046", "title": "Localization of the binding site for cell attachment in the alpha1(I) chain of collagen.", "content": "Certain cells such as CHO (Chinese hamster ovary) and fibroblasts attach to a substrate of type I collagen via proteins that link the cell surface to collagen. Serum contains a glycoprotein, c-CAP (collagen cell attachment protein), that can mediate this adhesion. Previously, we established that alpha1(I)-CB7 (cyanogen bromide peptide 7), which lies within residues 552 to 822 of collagen, contains a major binding site for c-CAP(alpha1(I)-CB7 has been renumbered to account for an additional triplet recently identified at residue 613 (P. P. Fietzek and R. W. Glanville, manuscript in preparation). Now we have examined the ability of various peptides derived by proteolytic digestion of alpha1(I)-CB7 to bind to c-CAP based upon their ability to inhibit cell attachment to collagen. The binding site lies within residues 757 to 791. It is likely that this is the sole binding site in the alpha1(I) chain since cleavage of the bond between residues 775 and 776 in the alpha1(I) chain destroys cell attachment activity.", "contents": "Localization of the binding site for cell attachment in the alpha1(I) chain of collagen. Certain cells such as CHO (Chinese hamster ovary) and fibroblasts attach to a substrate of type I collagen via proteins that link the cell surface to collagen. Serum contains a glycoprotein, c-CAP (collagen cell attachment protein), that can mediate this adhesion. Previously, we established that alpha1(I)-CB7 (cyanogen bromide peptide 7), which lies within residues 552 to 822 of collagen, contains a major binding site for c-CAP(alpha1(I)-CB7 has been renumbered to account for an additional triplet recently identified at residue 613 (P. P. Fietzek and R. W. Glanville, manuscript in preparation). Now we have examined the ability of various peptides derived by proteolytic digestion of alpha1(I)-CB7 to bind to c-CAP based upon their ability to inhibit cell attachment to collagen. The binding site lies within residues 757 to 791. It is likely that this is the sole binding site in the alpha1(I) chain since cleavage of the bond between residues 775 and 776 in the alpha1(I) chain destroys cell attachment activity."}
{"id": "PMID:209051", "title": "An H3 histone-specific kinase isolated from bovine thymus chromatin.", "content": "A substantial portion of the histone phosphorylating activity of bovine thymus chromatin can be isolated by extraction in 0.2 M NaCl. The specificity of this extract for either free histones or washed chromatin substrates was compared. The salt-extracted kinase enzymes favor H2b as the major acceptor when whole free histone is the substrate and H3 when the substrate is intact chromatin. The H3 kinase activity of bovine thymus tissue has been purified free from other detectable histone kinase activities by ammonium sulfate fractionation and is highly specific for H3 histone when assayed either with chromatin or isolated whole histone. The activity is cAMP-independent. Tryptic peptide mapping of the labeled H3 histone reveals a single site of phosphorylation. This site appears to be identical with the major site of metaphase-associated H3 phosphorylation in hepatoma tissue culture cells. No corresponding H3 phosphorylation has been detected in thymus tissue in vivo.", "contents": "An H3 histone-specific kinase isolated from bovine thymus chromatin. A substantial portion of the histone phosphorylating activity of bovine thymus chromatin can be isolated by extraction in 0.2 M NaCl. The specificity of this extract for either free histones or washed chromatin substrates was compared. The salt-extracted kinase enzymes favor H2b as the major acceptor when whole free histone is the substrate and H3 when the substrate is intact chromatin. The H3 kinase activity of bovine thymus tissue has been purified free from other detectable histone kinase activities by ammonium sulfate fractionation and is highly specific for H3 histone when assayed either with chromatin or isolated whole histone. The activity is cAMP-independent. Tryptic peptide mapping of the labeled H3 histone reveals a single site of phosphorylation. This site appears to be identical with the major site of metaphase-associated H3 phosphorylation in hepatoma tissue culture cells. No corresponding H3 phosphorylation has been detected in thymus tissue in vivo."}
{"id": "PMID:209052", "title": "Studies of cAMP metabolism in cultured hepatoma cells: presence of functional adenylate cyclase despite low cAMP content and lack of hormonal responsiveness.", "content": "The ability of isoproterenol, glucagon, PGE1 and cholera toxin to stimulate the synthesis of cAMP and protein kinase activity in line of liver cells (BRL) and a line of rat hepatoma cells (H35) has been determined. The concentration of cAMP in BRL cells (approximately 10 pmoles/mg protein) is in the range reported for other cultured cell lines but H35 cells contain extraordinarily low amounts of this cyclic nucleotide (approximately 0.05 pmoles/mg protein). Isoproterenol and PGE1 caused an increase in cAMP content, and protein kinase activation in BRL cells, although glucagon was ineffective. H35 cells, in contrast, were completely insensitive to all hormonal agonists. Despite this fact, cholera toxin was able to produce a marked increase in cAMP content, adenylate cyclase activity and protein kinase activation in H35 cells. binding studies with [125 I]-iodohydroxybenzylpindolol, a specific beta-adrenergic receptor antagonist, revealed that each H35 cell possesses fewer than 10 beta-adrenergic receptors whereas BRL cells contain 2-5,000 receptors per cell. The low level of cAMP in H35 cells appears to result from a combination of totally unstimulated adenylate cyclase and apparently elevated phosphodiesterase activities.", "contents": "Studies of cAMP metabolism in cultured hepatoma cells: presence of functional adenylate cyclase despite low cAMP content and lack of hormonal responsiveness. The ability of isoproterenol, glucagon, PGE1 and cholera toxin to stimulate the synthesis of cAMP and protein kinase activity in line of liver cells (BRL) and a line of rat hepatoma cells (H35) has been determined. The concentration of cAMP in BRL cells (approximately 10 pmoles/mg protein) is in the range reported for other cultured cell lines but H35 cells contain extraordinarily low amounts of this cyclic nucleotide (approximately 0.05 pmoles/mg protein). Isoproterenol and PGE1 caused an increase in cAMP content, and protein kinase activation in BRL cells, although glucagon was ineffective. H35 cells, in contrast, were completely insensitive to all hormonal agonists. Despite this fact, cholera toxin was able to produce a marked increase in cAMP content, adenylate cyclase activity and protein kinase activation in H35 cells. binding studies with [125 I]-iodohydroxybenzylpindolol, a specific beta-adrenergic receptor antagonist, revealed that each H35 cell possesses fewer than 10 beta-adrenergic receptors whereas BRL cells contain 2-5,000 receptors per cell. The low level of cAMP in H35 cells appears to result from a combination of totally unstimulated adenylate cyclase and apparently elevated phosphodiesterase activities."}
{"id": "PMID:209053", "title": "Studies on the association of the Epstein-Barr virus genome and human chromosomes.", "content": "We have used human-mouse somatic cell hybrid to study the association between the EBV genome and the cellular genome. Attempts were made to identify a specific human chromosome(s) with which the EBV genome is associated. Our data suggest that at least in the mouse fibroblast/Burkitt lymphoma hybrid combination studies, the EBV genome is not associated with any specific human chromosome.", "contents": "Studies on the association of the Epstein-Barr virus genome and human chromosomes. We have used human-mouse somatic cell hybrid to study the association between the EBV genome and the cellular genome. Attempts were made to identify a specific human chromosome(s) with which the EBV genome is associated. Our data suggest that at least in the mouse fibroblast/Burkitt lymphoma hybrid combination studies, the EBV genome is not associated with any specific human chromosome."}
{"id": "PMID:209054", "title": "Hormonal activation of adenylate cyclase in mouse melanoma metastatic variants.", "content": "The ability of melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), and prostaglandin E1 (PGE1) to stimulate the accumulation of cyclic AMP was examined in intact mouse melanoma cells of varying metastatic potential. F1 cells (low metastatic potential) had significantly greater cyclic AMP levels in response to all three hormones than F5 (intermediate metastatic potential) and F10 (high metastatic potential) cells. The ranking of the response was as follows: MSH, F1 greater than F5 greater than F10, ACTH, F1 greater than F5 greater F10, PGE, F1 greater than F10 greater F5. In contrast to the above, the degree of hormonal stimulation of adenylate cyclase in broken cell preparations was virtually identical in all three melanoma cell lines. Control enzyme activity was depressed in both F5 and F10 relative to F1. The conflicting results between studies of intact vs. broken cell preparations could not be explained by increased cyclic AMP phosphodiesterase activity in F5 and F10 cells. We conclude that as the melanoma cells increase in metastatic potential, there is a significant loss in the ability of their cyclic AMP system to respond appropriately to hormonal stimuli.", "contents": "Hormonal activation of adenylate cyclase in mouse melanoma metastatic variants. The ability of melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), and prostaglandin E1 (PGE1) to stimulate the accumulation of cyclic AMP was examined in intact mouse melanoma cells of varying metastatic potential. F1 cells (low metastatic potential) had significantly greater cyclic AMP levels in response to all three hormones than F5 (intermediate metastatic potential) and F10 (high metastatic potential) cells. The ranking of the response was as follows: MSH, F1 greater than F5 greater than F10, ACTH, F1 greater than F5 greater F10, PGE, F1 greater than F10 greater F5. In contrast to the above, the degree of hormonal stimulation of adenylate cyclase in broken cell preparations was virtually identical in all three melanoma cell lines. Control enzyme activity was depressed in both F5 and F10 relative to F1. The conflicting results between studies of intact vs. broken cell preparations could not be explained by increased cyclic AMP phosphodiesterase activity in F5 and F10 cells. We conclude that as the melanoma cells increase in metastatic potential, there is a significant loss in the ability of their cyclic AMP system to respond appropriately to hormonal stimuli."}
{"id": "PMID:209055", "title": "The role of phosphodiesterase in aggregation of Dictyostelium discoideum.", "content": "The role of cAMP phosphodiesterase in the cAMP-mediated aggregation of the cellular slime mould Dictyostelium discoideum was investigated with a morphogenetic mutant defective in phosphodiesterase production. Mutant cells become capable of aggregating normally when incubated in the presence of exogenous phosphodiesterase isolated from Idictyostelium or rat brain. Direct contact between enzyme and the cell membrane is not required for this phenotypic suppression. The aggregateless character of this strain presumably results from an over-accumulation of cAMP in the extracellular medium since aggregation can be induced in the absence of added phosphodiesterase under conditions facilitating diffusion of the nucleotide. This suggests that phosphodiesterase is not involved in the generation or recognition of cAMP signals, but that the enzyme is essential in the control of the cAMP signal-to-noise ratio.", "contents": "The role of phosphodiesterase in aggregation of Dictyostelium discoideum. The role of cAMP phosphodiesterase in the cAMP-mediated aggregation of the cellular slime mould Dictyostelium discoideum was investigated with a morphogenetic mutant defective in phosphodiesterase production. Mutant cells become capable of aggregating normally when incubated in the presence of exogenous phosphodiesterase isolated from Idictyostelium or rat brain. Direct contact between enzyme and the cell membrane is not required for this phenotypic suppression. The aggregateless character of this strain presumably results from an over-accumulation of cAMP in the extracellular medium since aggregation can be induced in the absence of added phosphodiesterase under conditions facilitating diffusion of the nucleotide. This suggests that phosphodiesterase is not involved in the generation or recognition of cAMP signals, but that the enzyme is essential in the control of the cAMP signal-to-noise ratio."}
{"id": "PMID:209056", "title": "Immune electron microscopy of avian infectious bronchitis virus serotypes.", "content": "An immune electron microscopy agglutination technique in which emphasis is placed upon the importance of antigen-antibody equivalence has been developed as a possible method for the serotyping of avian infectious bronchitis viruses. The Connecticut and Massachusetts 41 serotypes were used as a model system. Stock virus concentrations were standardized by physical particle counts of virions sedimented directly onto electron microscope specimen grids. Suspensions containing approximately 150 virions per grid square were allowed to react with dilutions of homologous and heterologous antisera. Virions in these constant virus-variable serum mixtures were sedimented directly onto electron microscope specimen grids, and the relative degree of aggregation per grid was determined from the mean percent aggregation of five randomly selected grid squares. In homologous assays, regions of relative antibody excess, of equivalence, and of relative antigen excess were clearly evident. At equivalence, the mean percent aggregation was significantly higher than in the regions of relative antibody or antigen excess. In the heterologous systems, the degree of aggregation differed little from that of the virus controls containing no antiserum.", "contents": "Immune electron microscopy of avian infectious bronchitis virus serotypes. An immune electron microscopy agglutination technique in which emphasis is placed upon the importance of antigen-antibody equivalence has been developed as a possible method for the serotyping of avian infectious bronchitis viruses. The Connecticut and Massachusetts 41 serotypes were used as a model system. Stock virus concentrations were standardized by physical particle counts of virions sedimented directly onto electron microscope specimen grids. Suspensions containing approximately 150 virions per grid square were allowed to react with dilutions of homologous and heterologous antisera. Virions in these constant virus-variable serum mixtures were sedimented directly onto electron microscope specimen grids, and the relative degree of aggregation per grid was determined from the mean percent aggregation of five randomly selected grid squares. In homologous assays, regions of relative antibody excess, of equivalence, and of relative antigen excess were clearly evident. At equivalence, the mean percent aggregation was significantly higher than in the regions of relative antibody or antigen excess. In the heterologous systems, the degree of aggregation differed little from that of the virus controls containing no antiserum."}
{"id": "PMID:209057", "title": "Hemoagglutination and hemagglutination inhibition tests with enterovirus type 70.", "content": "Human type \"O,\" guinea pig, and chicken erythrocytes were agglutinated by enterovirus type 70 at 4 degrees C or room temperature. A hemagglutination inhibition test, using human \"O\" erythrocytes, is described for the serological diagnosis of acute hemorrhagic conjunctivitis caused by enterovirus type 70.", "contents": "Hemoagglutination and hemagglutination inhibition tests with enterovirus type 70. Human type \"O,\" guinea pig, and chicken erythrocytes were agglutinated by enterovirus type 70 at 4 degrees C or room temperature. A hemagglutination inhibition test, using human \"O\" erythrocytes, is described for the serological diagnosis of acute hemorrhagic conjunctivitis caused by enterovirus type 70."}
{"id": "PMID:209058", "title": "Noncultivable viruses and neonatal diarrhea: fifteen-month survey in a newborn special care nursery.", "content": "During a 15-month period of surveillance, diarrhea developed in 257 of 913 babies (28%) admitted within 2 hours of birth to a special care nursery in Melbourne, Australia. Diarrhea was seasonal, affecting a maximum of 43% of babies admitted during one winter month (July) and a minimum of 13% of babies admitted during one summer month (December). Diarrhea was no more frequent nor more severe in babies of very low birth weight or of very early gestational age. Two noncultivable viruses were located by electron microscopy in feces from babies with or without diarrhea. Excretion of a reovirus-like particle (rotavirus, duovirus, human reovirus-like agent, infantile gastroenteritis virus) was temporally related to diarrheal symptoms. Asymptomatic infection with this virus also occurred. A 28-nm virus-like particle was excreted by some babies, but it could not be implicated on epidemiological grounds in the etiology of the diarrhea. Rotavirus infection may be an important cause of endemic diarrhea in nurseries for the newborn. Infection may be difficult to control or eradicate, since it is often asymptomatic and may be influenced by infection in the community at large.", "contents": "Noncultivable viruses and neonatal diarrhea: fifteen-month survey in a newborn special care nursery. During a 15-month period of surveillance, diarrhea developed in 257 of 913 babies (28%) admitted within 2 hours of birth to a special care nursery in Melbourne, Australia. Diarrhea was seasonal, affecting a maximum of 43% of babies admitted during one winter month (July) and a minimum of 13% of babies admitted during one summer month (December). Diarrhea was no more frequent nor more severe in babies of very low birth weight or of very early gestational age. Two noncultivable viruses were located by electron microscopy in feces from babies with or without diarrhea. Excretion of a reovirus-like particle (rotavirus, duovirus, human reovirus-like agent, infantile gastroenteritis virus) was temporally related to diarrheal symptoms. Asymptomatic infection with this virus also occurred. A 28-nm virus-like particle was excreted by some babies, but it could not be implicated on epidemiological grounds in the etiology of the diarrhea. Rotavirus infection may be an important cause of endemic diarrhea in nurseries for the newborn. Infection may be difficult to control or eradicate, since it is often asymptomatic and may be influenced by infection in the community at large."}
{"id": "PMID:209059", "title": "Selective uptake of the synthetic amino terminal fragment of bovine parathyroid hormone by isolated perfused bone.", "content": "Studies from our laboratory have shown that the metabolic clearance rate of carboxy terminal immunoreactive parathyroid hormone (i-PTH) can be accounted for by extraction of i-PTH by liver and kidney. In contrast, there was no demonstrable hepatic uptake of the synthetic amino terminal bovine PTH fragment (syn b-PTH 1-34) and the kidney accounted for only 45% of the metabolic clearance rate of amino terminal i-PTH. This suggested that another major site, presumably bone, played a role in the metabolism of syn b-PTH 1-34. Extraction of i-PTH by isolated perfused bone was studied during infusion of purified bovine PTH (b-PTH) 1-84 or syn b-PTH 1-34. In five studies during infusion of syn b-PTH 1-34 the arteriovenous difference for i-PTH across bone was 36%. In contrast, no significant uptake of carboxy terminal i-PTH was observed in nine studies during infusion of b-PTH 1-84. In addition, when H(2)O(2)-oxidized (biologically inactive) syn b-PTH 1-34 was used no arteriovenous difference was observed. These findings correlated with the ability of these PTH preparations to stimulate cyclic AMP production by the perfused bone. Syn b-PTH 1-34 increased cyclic AMP production at perfusate PTH concentrations of 1-5 ng/ml, whereas b-PTH 1-84 evoked only a minimal response at concentrations of 10-20 ng/ml. We conclude that bone is a major site of metabolism of the amino terminal PTH fragment, syn b-PTH 1-34. In addition, these data suggest that cleavage of the intact hormone, with the production of amino terminal PTH fragments by peripheral organs (liver and kidney), may play a major role in the regulation of PTH effects on bone.", "contents": "Selective uptake of the synthetic amino terminal fragment of bovine parathyroid hormone by isolated perfused bone. Studies from our laboratory have shown that the metabolic clearance rate of carboxy terminal immunoreactive parathyroid hormone (i-PTH) can be accounted for by extraction of i-PTH by liver and kidney. In contrast, there was no demonstrable hepatic uptake of the synthetic amino terminal bovine PTH fragment (syn b-PTH 1-34) and the kidney accounted for only 45% of the metabolic clearance rate of amino terminal i-PTH. This suggested that another major site, presumably bone, played a role in the metabolism of syn b-PTH 1-34. Extraction of i-PTH by isolated perfused bone was studied during infusion of purified bovine PTH (b-PTH) 1-84 or syn b-PTH 1-34. In five studies during infusion of syn b-PTH 1-34 the arteriovenous difference for i-PTH across bone was 36%. In contrast, no significant uptake of carboxy terminal i-PTH was observed in nine studies during infusion of b-PTH 1-84. In addition, when H(2)O(2)-oxidized (biologically inactive) syn b-PTH 1-34 was used no arteriovenous difference was observed. These findings correlated with the ability of these PTH preparations to stimulate cyclic AMP production by the perfused bone. Syn b-PTH 1-34 increased cyclic AMP production at perfusate PTH concentrations of 1-5 ng/ml, whereas b-PTH 1-84 evoked only a minimal response at concentrations of 10-20 ng/ml. We conclude that bone is a major site of metabolism of the amino terminal PTH fragment, syn b-PTH 1-34. In addition, these data suggest that cleavage of the intact hormone, with the production of amino terminal PTH fragments by peripheral organs (liver and kidney), may play a major role in the regulation of PTH effects on bone."}
{"id": "PMID:209060", "title": "Activation of adenylate cyclase by heat-labile Escherichia coli enterotoxin. Evidence for ADP-ribosyltransferase activity similar to that of choleragen.", "content": "Highly purified, polymyxin-released, low molecular weight Escherichia coli heat-labile enterotoxin (LT) catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide. This NAD glycohydrolase activity was stimulated by dithiothreitol and was independent of cellular components. Nicotinamide formation was enhanced by arginine methyl ester > d-arginine congruent with l-arginine congruent with guanidine. A 20-fold increase in activity was noted with arginine methyl ester, and maximal activity again required dithiothreitol. When the reaction was initiated with toxin, a delay was observed before a constant rate was established. The reaction products found after incubation of [adenine-U-(14)C]NAD and l-[(3)H]arginine or unlabeled arginine methyl ester with the enterotoxin had mobilities on thin-layer chromatograms similar to the reaction products obtained after incubation of choleragen with these substrates and are consistent with the formation of ADP-ribose-l-arginine and ADP-ribose-l-arginine methyl ester, respectively. Both toxins, which catalyze the NAD-dependent activation of adenylate cyclase, thus appear to possess NAD glycohydrolase and ADP-ribosyltransferase activities. Although the activities of both toxins are dependent on dithiothreitol, Escherichia coli enterotoxin exhibited optimal activity in Tris (Cl(-)) (pH 7.5) and was inhibited by high concentrations of potassium phosphate (pH 7.0) or low pH (sodium acetate, pH 6.2). It appears that the optimal assay conditions as well as the kinetic constants for the reactants differ from those previously noted with choleragen. It is probable therefore that although the two toxins catalyze similar reactions, they differ in primary structure. The presence of transferase and glycohydrolase activities in structurally distinct toxins that activate adenylate cyclase strengthens our hypothesis that the ADP-ribosylation of arginine is a model for the NAD-dependent activation of adenylate cyclase; activation may result from ADP-ribosylation of the cyclase itself or of a protein that regulates its activity.", "contents": "Activation of adenylate cyclase by heat-labile Escherichia coli enterotoxin. Evidence for ADP-ribosyltransferase activity similar to that of choleragen. Highly purified, polymyxin-released, low molecular weight Escherichia coli heat-labile enterotoxin (LT) catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide. This NAD glycohydrolase activity was stimulated by dithiothreitol and was independent of cellular components. Nicotinamide formation was enhanced by arginine methyl ester > d-arginine congruent with l-arginine congruent with guanidine. A 20-fold increase in activity was noted with arginine methyl ester, and maximal activity again required dithiothreitol. When the reaction was initiated with toxin, a delay was observed before a constant rate was established. The reaction products found after incubation of [adenine-U-(14)C]NAD and l-[(3)H]arginine or unlabeled arginine methyl ester with the enterotoxin had mobilities on thin-layer chromatograms similar to the reaction products obtained after incubation of choleragen with these substrates and are consistent with the formation of ADP-ribose-l-arginine and ADP-ribose-l-arginine methyl ester, respectively. Both toxins, which catalyze the NAD-dependent activation of adenylate cyclase, thus appear to possess NAD glycohydrolase and ADP-ribosyltransferase activities. Although the activities of both toxins are dependent on dithiothreitol, Escherichia coli enterotoxin exhibited optimal activity in Tris (Cl(-)) (pH 7.5) and was inhibited by high concentrations of potassium phosphate (pH 7.0) or low pH (sodium acetate, pH 6.2). It appears that the optimal assay conditions as well as the kinetic constants for the reactants differ from those previously noted with choleragen. It is probable therefore that although the two toxins catalyze similar reactions, they differ in primary structure. The presence of transferase and glycohydrolase activities in structurally distinct toxins that activate adenylate cyclase strengthens our hypothesis that the ADP-ribosylation of arginine is a model for the NAD-dependent activation of adenylate cyclase; activation may result from ADP-ribosylation of the cyclase itself or of a protein that regulates its activity."}
{"id": "PMID:209061", "title": "Bone marrow-derived lymphoid cell lines from patients with agammaglobulinemia.", "content": "In vitro infection with Epstein-Barr virus of bone marrow-derived (B) lymphocytes from blood of patients with X-linked or common varied agammaglobulinemia resulted in the establishment of long-term B-lymphoid cell lines (LCL). LCL were established only with B lymphocytes from patients whose B cells failed to respond to in vitro mitogenic stimulation. In contrast, lymphocytes from patients without small B lymphocytes or with B cells that synthesized but failed to secrete Ig failed uniformly to establish LCL. Analysis of the \"nonsecretory\" B lymphocytes demonstrated the presence of receptors for C3b and C3d as well as surface Ig, but absence of detectable receptors for Epstein-Barr virus. All of the six cell lines that were established formed rosettes with EAC3 but not with sheep erythrocytes. Four of the six LCL were principally surface IgD bearing and did not synthesize detectable Ig for secretion. Two of the cell lines were indistinguishable from cell lines from normal individuals: they had surface IgG, A, M, and D and synthesized and secreted Ig.", "contents": "Bone marrow-derived lymphoid cell lines from patients with agammaglobulinemia. In vitro infection with Epstein-Barr virus of bone marrow-derived (B) lymphocytes from blood of patients with X-linked or common varied agammaglobulinemia resulted in the establishment of long-term B-lymphoid cell lines (LCL). LCL were established only with B lymphocytes from patients whose B cells failed to respond to in vitro mitogenic stimulation. In contrast, lymphocytes from patients without small B lymphocytes or with B cells that synthesized but failed to secrete Ig failed uniformly to establish LCL. Analysis of the \"nonsecretory\" B lymphocytes demonstrated the presence of receptors for C3b and C3d as well as surface Ig, but absence of detectable receptors for Epstein-Barr virus. All of the six cell lines that were established formed rosettes with EAC3 but not with sheep erythrocytes. Four of the six LCL were principally surface IgD bearing and did not synthesize detectable Ig for secretion. Two of the cell lines were indistinguishable from cell lines from normal individuals: they had surface IgG, A, M, and D and synthesized and secreted Ig."}
{"id": "PMID:209062", "title": "Interaction of diphenylhydantoin (phenytoin) and phenobarbital with hormonal mediation of fetal rat bone resorption in vitro.", "content": "Chronic administration of high doses of anticonvulsant drugs frequently produces classic osteomalacia with bone histologic changes characteristic of increased parathyroid hormone (PTH) effect in man. However, several reports have documented defects in calcified tissue metabolism suggestive of an end-organ resistance to PTH after chronic anticonvulsant drug therapy. To examine the direct action of anticonvulsant drugs on bone resorption, we investigated the effects of diphenylhydantoin (phenytoin) (DPH) (100-200 mug/ml) and phenobarbital (10-400 mug/ml) on basal and hormonally mediated resorption 5-day cultures of fetal rat forelimb rudiments. In this system both drugs significantly inhibited basal and PTH-stimulated (45)Ca and [(3)H]hydroxyproline release, as well as 1,25-dihydroxyvitamin D(3)-stimulated (45)Ca release. The effects of DPH and phenobarbital were additive, with DPH exhibiting a several-fold more potent inhibitory effect than phenobarbital. Whereas DPH exhibited a striking synergism with the inhibitory effects of human calcitonin (HCT) on PTH-induced resorption, the effect of phenobarbital was merely additive to that of HCT. PTH and PTH plus HCT-induced increases in bone cyclic AMP (cAMP) content were significantly inhibited by DPH but not by phenobarbital. However, in contrast to effects on (45)Ca release, DPH inhibition of cAMP generation was not accentuated in the presence of HCT. It is concluded that: (a) both DPH and phenobarbital can directly inhibit basal and hormonally stimulated bone resorption, with DPH being much more potent in this regard; (b) DPH appears to inhibit bone resorption via a cAMP-independent mechanism and has an additional suppressive effect on PTH-induced cAMP generation; and (c) the synergistic interaction of DPH and HCT in inhibiting (45)Ca release occurs at a site independent of cAMP generation.", "contents": "Interaction of diphenylhydantoin (phenytoin) and phenobarbital with hormonal mediation of fetal rat bone resorption in vitro. Chronic administration of high doses of anticonvulsant drugs frequently produces classic osteomalacia with bone histologic changes characteristic of increased parathyroid hormone (PTH) effect in man. However, several reports have documented defects in calcified tissue metabolism suggestive of an end-organ resistance to PTH after chronic anticonvulsant drug therapy. To examine the direct action of anticonvulsant drugs on bone resorption, we investigated the effects of diphenylhydantoin (phenytoin) (DPH) (100-200 mug/ml) and phenobarbital (10-400 mug/ml) on basal and hormonally mediated resorption 5-day cultures of fetal rat forelimb rudiments. In this system both drugs significantly inhibited basal and PTH-stimulated (45)Ca and [(3)H]hydroxyproline release, as well as 1,25-dihydroxyvitamin D(3)-stimulated (45)Ca release. The effects of DPH and phenobarbital were additive, with DPH exhibiting a several-fold more potent inhibitory effect than phenobarbital. Whereas DPH exhibited a striking synergism with the inhibitory effects of human calcitonin (HCT) on PTH-induced resorption, the effect of phenobarbital was merely additive to that of HCT. PTH and PTH plus HCT-induced increases in bone cyclic AMP (cAMP) content were significantly inhibited by DPH but not by phenobarbital. However, in contrast to effects on (45)Ca release, DPH inhibition of cAMP generation was not accentuated in the presence of HCT. It is concluded that: (a) both DPH and phenobarbital can directly inhibit basal and hormonally stimulated bone resorption, with DPH being much more potent in this regard; (b) DPH appears to inhibit bone resorption via a cAMP-independent mechanism and has an additional suppressive effect on PTH-induced cAMP generation; and (c) the synergistic interaction of DPH and HCT in inhibiting (45)Ca release occurs at a site independent of cAMP generation."}
{"id": "PMID:209063", "title": "Ectopic ACTH syndrome: clinicopathological correlations.", "content": "Ten out of 164 cases of bronchogenic carcinoma showed pathological evidence at necropsy of the ectopic ACTH syndrome. All occurred in association with oat-cell carcinoma, constituting 19% of that group. The pathological features consisted of adrenocortical hyperplasia confined to the zona fasciculata and Crooke's hyaline change in the pituitary. Immunoperoxidase stainable ACTH was detected in the pituitary but not in the carcinoma tissue, a surprising finding, which may be due to the different nature of ACTH present in tumour tissue. The ectopic ACTH syndrome was diagnosed ante mortem in only four out of 10 patients on the basis of hypokalaemia and metabolic alkalosis. The lack of clinical pointers in all but terminal cases is discussed as well as possible measures for earlier diagnosis.", "contents": "Ectopic ACTH syndrome: clinicopathological correlations. Ten out of 164 cases of bronchogenic carcinoma showed pathological evidence at necropsy of the ectopic ACTH syndrome. All occurred in association with oat-cell carcinoma, constituting 19% of that group. The pathological features consisted of adrenocortical hyperplasia confined to the zona fasciculata and Crooke's hyaline change in the pituitary. Immunoperoxidase stainable ACTH was detected in the pituitary but not in the carcinoma tissue, a surprising finding, which may be due to the different nature of ACTH present in tumour tissue. The ectopic ACTH syndrome was diagnosed ante mortem in only four out of 10 patients on the basis of hypokalaemia and metabolic alkalosis. The lack of clinical pointers in all but terminal cases is discussed as well as possible measures for earlier diagnosis."}
{"id": "PMID:209064", "title": "A case of type III hyperlipoproteinaemia studied by acrylamide gel gradient electrophoresis.", "content": "A case of type III hyperlipoproteinaemia has been investigated before and after treatment, and the unusual serum lipoprotein patterns obtained by molecular exclusion or pore limit electrophoresis on acrylamide gradients have been compared.", "contents": "A case of type III hyperlipoproteinaemia studied by acrylamide gel gradient electrophoresis. A case of type III hyperlipoproteinaemia has been investigated before and after treatment, and the unusual serum lipoprotein patterns obtained by molecular exclusion or pore limit electrophoresis on acrylamide gradients have been compared."}
{"id": "PMID:209065", "title": "Demonstration of saturation kinetics in the intestinal absorption of vitamin C in man and the guinea pig.", "content": "Intestinal absorption of ascorbic acid is believed to be mediated through a sodium-dependent active transport process in man and in the guinea pig, both species having a nutritional requirement for the vitamin. Vitamin C transport was studied in man and in the guinea pig by in vivo intestinal perfusion of concentrations of vitamin C ranging from physiologic to clearly pharmacologic levels. Triple lumen intestinal perfusion of seven human volunteers with vitamin C concentrations ranging from 0.85 to 11.36 mM demonstrated saturation kinetics of absorption with a Km = 5.44 mM. Net secretion of water was observed in three of seven humans with the highest (11.36 mM) concentration of vitamin C. Perfusion of isolated segments of guinea pig intestines with intact blood supply also revealed saturation kinetics (Km = 5.54 mM) in the range of 1.42 to 56.8 mM vitamin C but linear absorption below this range. The phenomenon of decreased water absorption noted with incremental vitamin C dose in human volunteers could not be reproduced in the guinea pig, nor were the intestinal tissue levels of cyclic AMP and GMP increased by high-dose vitamin C in this species. This study suggests that \"megavitamin\" doses of vitamin C (greater than 1 Gm) are probably not as efficiently absorbed as smaller multiple doses of the vitamin. Intestinal secretion of water may contribute to the diarrhea which is the most common side effect of large doses of vitamin C. The guinea pig is a useful but limited model for vitamin C absorption in man.", "contents": "Demonstration of saturation kinetics in the intestinal absorption of vitamin C in man and the guinea pig. Intestinal absorption of ascorbic acid is believed to be mediated through a sodium-dependent active transport process in man and in the guinea pig, both species having a nutritional requirement for the vitamin. Vitamin C transport was studied in man and in the guinea pig by in vivo intestinal perfusion of concentrations of vitamin C ranging from physiologic to clearly pharmacologic levels. Triple lumen intestinal perfusion of seven human volunteers with vitamin C concentrations ranging from 0.85 to 11.36 mM demonstrated saturation kinetics of absorption with a Km = 5.44 mM. Net secretion of water was observed in three of seven humans with the highest (11.36 mM) concentration of vitamin C. Perfusion of isolated segments of guinea pig intestines with intact blood supply also revealed saturation kinetics (Km = 5.54 mM) in the range of 1.42 to 56.8 mM vitamin C but linear absorption below this range. The phenomenon of decreased water absorption noted with incremental vitamin C dose in human volunteers could not be reproduced in the guinea pig, nor were the intestinal tissue levels of cyclic AMP and GMP increased by high-dose vitamin C in this species. This study suggests that \"megavitamin\" doses of vitamin C (greater than 1 Gm) are probably not as efficiently absorbed as smaller multiple doses of the vitamin. Intestinal secretion of water may contribute to the diarrhea which is the most common side effect of large doses of vitamin C. The guinea pig is a useful but limited model for vitamin C absorption in man."}
{"id": "PMID:209071", "title": "Surgical treatment of submucosal tumors of the hard palate.", "content": "Two cases have been presented to illustrated to illustrate the principles of total excisional biopsy for palatal tumors and the postoperative management of the resulting defect with the use of palatal splints. Total excisional biopsy is curative for benign tumors and for some malignant-grade tumors, and is the preferred method of treatment when possible. Total excision of the lesion with adequate margins negates the possibility of seeding the tumor into surrounding tissue or of leaving behind residual tumor.", "contents": "Surgical treatment of submucosal tumors of the hard palate. Two cases have been presented to illustrated to illustrate the principles of total excisional biopsy for palatal tumors and the postoperative management of the resulting defect with the use of palatal splints. Total excisional biopsy is curative for benign tumors and for some malignant-grade tumors, and is the preferred method of treatment when possible. Total excision of the lesion with adequate margins negates the possibility of seeding the tumor into surrounding tissue or of leaving behind residual tumor."}
{"id": "PMID:209072", "title": "A review of marijuana in relation to stress-response mechanisms in the dental patient.", "content": "A comprehensive review of the established physiologic and metabolic effects of marijuana in relation to cardiovascular physiology and stress-response mechanisms has been presented. This information is related to the preoperative and postoperative treatment of the dental patient who smokes marijuana habitually. Marijuana is not a benign drug. Its vasoactive, cardiotropic, steroidogenic, and enhanced sympathoadrenal stress-response effects justify caution when administering atropine or epinephrine-containing products to the habitual user of marijuana. More clinical as well as laboratory research is needed to elucidate the speculation regarding a drug so frequently misused.", "contents": "A review of marijuana in relation to stress-response mechanisms in the dental patient. A comprehensive review of the established physiologic and metabolic effects of marijuana in relation to cardiovascular physiology and stress-response mechanisms has been presented. This information is related to the preoperative and postoperative treatment of the dental patient who smokes marijuana habitually. Marijuana is not a benign drug. Its vasoactive, cardiotropic, steroidogenic, and enhanced sympathoadrenal stress-response effects justify caution when administering atropine or epinephrine-containing products to the habitual user of marijuana. More clinical as well as laboratory research is needed to elucidate the speculation regarding a drug so frequently misused."}
{"id": "PMID:209105", "title": "Cyclic 3',5'-nucleotide phosphodiesterase; cytochemical localization in rat renomedullary interstitial cells.", "content": "The localization of cyclic 3', 5' -nucleotide phosphodiesterase activity in rat renal papillae was examined by utilizing cytochemical methods. Renal medullary interstitial cells had predictable phosphodiesterase activity predominantly on the cytoplasmic border of dilated cisternal membranes. Cells of the collecting tubule and loop of Henle contained diffuse reaction product. Capillaries had reaction product localized in pinocytic vesicles. Addition of theophylline resulted in no deposition of reaction product in interstitial cells and in cells of the collecting tubule and loop of Henle, suggesting an inhibition of phosphodiesterase activity. Since the membranes of dilated cisternae of renal medullary interstitial cells have been shown to be related to prostaglandin synthesis and probably to the anti-hypertensive function of these cells, the finding of phosphodiesterase activity on these membranes suggests a possible role of cyclic AMP in these two functions.", "contents": "Cyclic 3',5'-nucleotide phosphodiesterase; cytochemical localization in rat renomedullary interstitial cells. The localization of cyclic 3', 5' -nucleotide phosphodiesterase activity in rat renal papillae was examined by utilizing cytochemical methods. Renal medullary interstitial cells had predictable phosphodiesterase activity predominantly on the cytoplasmic border of dilated cisternal membranes. Cells of the collecting tubule and loop of Henle contained diffuse reaction product. Capillaries had reaction product localized in pinocytic vesicles. Addition of theophylline resulted in no deposition of reaction product in interstitial cells and in cells of the collecting tubule and loop of Henle, suggesting an inhibition of phosphodiesterase activity. Since the membranes of dilated cisternae of renal medullary interstitial cells have been shown to be related to prostaglandin synthesis and probably to the anti-hypertensive function of these cells, the finding of phosphodiesterase activity on these membranes suggests a possible role of cyclic AMP in these two functions."}
{"id": "PMID:209106", "title": "Glucocorticoid receptors and glucocorticoid-sensitive secretion of neutral proteinases in a macrophage line.", "content": "A continuous line of mouse macrophages (P388D1) has been shown to secrete elastase, collagenase, and plasminogen activator at activities comparable to those of macrophages elicited by an inflammatory stimulus in vivo. At physiologic concentrations anti-inflammatory glucocorticoids selectively and reversibly inhibited secretion of the three proteinases but did not inhibit secretion of lysozyme, a constitutive enzyme produced by the P388D1 cells. The secretion of the neutral proteinases was inhibited 50% by 2 to 10 nM dexamethasone. Proliferation of the macrophages was also glucocorticoid sensitive. The P388D1 macrophages contained about 4000 saturable glucocorticoid-binding sites per cell. Concentrations of hormone saturating the high affinity receptor site (for dexamethasone the dissociation constant for steroid-receptor binding, Kd, was 4 nM) correlated well with concentrations inhibiting secretion of the proteinases. Only glucocorticoids and progesterone competed for binding to the specific receptors. Temperature-sensitive translocation of hormone-receptor complexes from \"cytoplasm\" to nucleus similar to that found with rat thymocytes was demonstrated. Thus, the interaction between glucocorticoids and the P388D1 cell line provides a model for the regulation of macrophage secretion of neutral proteinases under normal and stress conditions.", "contents": "Glucocorticoid receptors and glucocorticoid-sensitive secretion of neutral proteinases in a macrophage line. A continuous line of mouse macrophages (P388D1) has been shown to secrete elastase, collagenase, and plasminogen activator at activities comparable to those of macrophages elicited by an inflammatory stimulus in vivo. At physiologic concentrations anti-inflammatory glucocorticoids selectively and reversibly inhibited secretion of the three proteinases but did not inhibit secretion of lysozyme, a constitutive enzyme produced by the P388D1 cells. The secretion of the neutral proteinases was inhibited 50% by 2 to 10 nM dexamethasone. Proliferation of the macrophages was also glucocorticoid sensitive. The P388D1 macrophages contained about 4000 saturable glucocorticoid-binding sites per cell. Concentrations of hormone saturating the high affinity receptor site (for dexamethasone the dissociation constant for steroid-receptor binding, Kd, was 4 nM) correlated well with concentrations inhibiting secretion of the proteinases. Only glucocorticoids and progesterone competed for binding to the specific receptors. Temperature-sensitive translocation of hormone-receptor complexes from \"cytoplasm\" to nucleus similar to that found with rat thymocytes was demonstrated. Thus, the interaction between glucocorticoids and the P388D1 cell line provides a model for the regulation of macrophage secretion of neutral proteinases under normal and stress conditions."}
{"id": "PMID:209107", "title": "Independent stimulation of motility and the oxidative metabolic burst of human polymorphonuclear leukocytes.", "content": "It has recently been suggested that a single stimulus to the membrane of the polymorphonuclear neutrophil leukocyte (PMN) produces a sequential, stereotyped response involving motility, degranulation, and the oxidative metabolic burst, and conversely, that the chemotactic response is dependent upon the stimulation of the hexose monophosphate shunt (HMPS). We have used small, synthetic substances, known to cause either increased motility or the metabolic burst, to examine whether these events can be stimulated independently. Phorbol myristate acetate (PMA) is a surface active agent that causes marked stimulation of iodination, superoxide production, chemiluminescence, and the HMPS. Such stimulation by PMA did not alter random or directional motility of PMN in the chemotaxis-under-agarose assay. Also, preincubation of PMN with PMA did not deplete their energy source for chemotaxis as demonstrated by a normal chemotactic response to zymosan activated serum. N-formylmethionyl peptides (f-met-phe, f-met-leu-phe) caused a dose-related stimulation of random and directional motility of PMN, but only a very slight stimulation of the HMPS, protein iodination, superoxide production, or chemiluminescence, and this minimal response occurred at more than 1000 times the concentration needed for stimulation of motility. These results indicate that stimulation of motility in the metabolic burst may involve separate events at the membrane of the PMN and that the events are not necessarily interdependent.", "contents": "Independent stimulation of motility and the oxidative metabolic burst of human polymorphonuclear leukocytes. It has recently been suggested that a single stimulus to the membrane of the polymorphonuclear neutrophil leukocyte (PMN) produces a sequential, stereotyped response involving motility, degranulation, and the oxidative metabolic burst, and conversely, that the chemotactic response is dependent upon the stimulation of the hexose monophosphate shunt (HMPS). We have used small, synthetic substances, known to cause either increased motility or the metabolic burst, to examine whether these events can be stimulated independently. Phorbol myristate acetate (PMA) is a surface active agent that causes marked stimulation of iodination, superoxide production, chemiluminescence, and the HMPS. Such stimulation by PMA did not alter random or directional motility of PMN in the chemotaxis-under-agarose assay. Also, preincubation of PMN with PMA did not deplete their energy source for chemotaxis as demonstrated by a normal chemotactic response to zymosan activated serum. N-formylmethionyl peptides (f-met-phe, f-met-leu-phe) caused a dose-related stimulation of random and directional motility of PMN, but only a very slight stimulation of the HMPS, protein iodination, superoxide production, or chemiluminescence, and this minimal response occurred at more than 1000 times the concentration needed for stimulation of motility. These results indicate that stimulation of motility in the metabolic burst may involve separate events at the membrane of the PMN and that the events are not necessarily interdependent."}
{"id": "PMID:209110", "title": "Altered subcellular and submitochondrial localization of CTP:phosphatidate cytidylyltransferase in the Morris 7777 hepatoma.", "content": "The subcellular and submitochondrial localization of CTP:phosphatidate cytidylyltransferase is altered in the Morris 7777 hepatoma. Mitochondria in this poorly differentiated tumor are the principal sites of CDP-diacylglycerol synthesis, in contrast to normal rat liver where the endoplasmic reticulum is most active. This enzyme activity was increased 17-fold in the outer mitochondrial membrane, and a 22% increase was noted in the inner mitochondrial membrane of the 7777 hepatoma as compared with the corresponding fractions from normal rat liver. Increased mitochondrial CTP:phosphatidate cytidylyltransferase was present in six other Morris hepatomas, but it was not found in fetal rat liver mitochondria, suggesting that rapid growth alone is not responsible for the difference. Evidence is presented which indicates that mitochondrial lipid degradation is similar in normal liver and the 7777 hepatoma, in vitro. The increased activity of CTP: phosphatidate cytidylytransferase is thought to be responsible in part for the moderately increased diphosphatidylglycerol content of 7777 hepatoma mitochondria.", "contents": "Altered subcellular and submitochondrial localization of CTP:phosphatidate cytidylyltransferase in the Morris 7777 hepatoma. The subcellular and submitochondrial localization of CTP:phosphatidate cytidylyltransferase is altered in the Morris 7777 hepatoma. Mitochondria in this poorly differentiated tumor are the principal sites of CDP-diacylglycerol synthesis, in contrast to normal rat liver where the endoplasmic reticulum is most active. This enzyme activity was increased 17-fold in the outer mitochondrial membrane, and a 22% increase was noted in the inner mitochondrial membrane of the 7777 hepatoma as compared with the corresponding fractions from normal rat liver. Increased mitochondrial CTP:phosphatidate cytidylyltransferase was present in six other Morris hepatomas, but it was not found in fetal rat liver mitochondria, suggesting that rapid growth alone is not responsible for the difference. Evidence is presented which indicates that mitochondrial lipid degradation is similar in normal liver and the 7777 hepatoma, in vitro. The increased activity of CTP: phosphatidate cytidylytransferase is thought to be responsible in part for the moderately increased diphosphatidylglycerol content of 7777 hepatoma mitochondria."}
{"id": "PMID:209111", "title": "Protein kinase-mediated phosphorylation of a purified sterol ester hydrolase from bovine adrenal cortex.", "content": "Sterol ester hydrolase (cholesterol esterase, E.C. 3.1.1.13) of bovine adrenal cortex has been extensively purified by ammonium sulfate fractionation, acid precipitation, hydroxylapatite chromatography, and Sephadex G-200 chromatography. During the purification sequence, the hydrolase activity was purified free of endogenous protein kinase. With this purified preparation, activation by cyclic AMP and ATP-Mg2+ did not occur unless exogenous protein kinase was included in the activating system. Using [gamma-32P]ATP, the transfer of the terminal phosphate to the enzyme protein was demonstrated by three separate experimental approaches. With pooled fractions from Sephadex G-200 chromatography, significant binding of 32P by the enzyme protein was observed only in the presence of exogenous protein kinase. Time course studies disclosed a close concurrence between the extent of activation of the purified enzyme by cyclic AMP-dependent protein kinase and the level of 32P transfer from [gamma-32P]ATP to the enzyme protein. Finally, assays carried out during Sephadex G-200 chromatography showed a correspondence in the peaks for activated sterol ester hydrolase and for 32P binding by protein. The data confirm that activation of adrenal sterol ester hydrolase by cyclic AMP and ATP-Mg2+ involves protein kinase-catalyzed phosphorylation of the enzyme protein.", "contents": "Protein kinase-mediated phosphorylation of a purified sterol ester hydrolase from bovine adrenal cortex. Sterol ester hydrolase (cholesterol esterase, E.C. 3.1.1.13) of bovine adrenal cortex has been extensively purified by ammonium sulfate fractionation, acid precipitation, hydroxylapatite chromatography, and Sephadex G-200 chromatography. During the purification sequence, the hydrolase activity was purified free of endogenous protein kinase. With this purified preparation, activation by cyclic AMP and ATP-Mg2+ did not occur unless exogenous protein kinase was included in the activating system. Using [gamma-32P]ATP, the transfer of the terminal phosphate to the enzyme protein was demonstrated by three separate experimental approaches. With pooled fractions from Sephadex G-200 chromatography, significant binding of 32P by the enzyme protein was observed only in the presence of exogenous protein kinase. Time course studies disclosed a close concurrence between the extent of activation of the purified enzyme by cyclic AMP-dependent protein kinase and the level of 32P transfer from [gamma-32P]ATP to the enzyme protein. Finally, assays carried out during Sephadex G-200 chromatography showed a correspondence in the peaks for activated sterol ester hydrolase and for 32P binding by protein. The data confirm that activation of adrenal sterol ester hydrolase by cyclic AMP and ATP-Mg2+ involves protein kinase-catalyzed phosphorylation of the enzyme protein."}
{"id": "PMID:209112", "title": "ACTH-induced hydrolysis of cholesteryl esters in rat adrenal cells.", "content": "Rat adrenal cortical cells have been prepared by collagenase dissociation of trypsin-treated adrenal tissue. The content and compositions of cholesteryl ester, phospholipid, and triglyceride fatty acids compare favorably with those of undissociated rat adrenal tissue. During 2-hour control incubations of adrenal cortical cells, steroidogenesis was not detected, and the levels of sterol ester, phospholipid, and triglyceride fatty acids were not significantly altered. Incubations with adrenocorticotropic hormone (ACTH) resulted in coricosterone production and significant depletions of sterol ester and triglyceride fatty acids, but not of phospholipid fatty acids. Although all fatty acid esters of cholesterol were hydrolyzed under these conditions, the greatest contributions to the net decrease in sterol esters were by oleate, arachidonate, and adrenate. Incubations with dibutyryl cyclic adenosine monophosphate (0.5 mM) resulted in significantly greater levels of corticosterone production than did ACTH (250 muunits), but the effects on cellular lipids were comparable to those seen with the tropic hormone. This study represents the first demonstration of hormone-induced hydrolysis of sterol esters in an in vitro cell suspension system. The results are discussed with respect to hormone-sensitive sterol ester hydrolase of adrenal cortex, and to the role of endogenous cholesteryl esters in the steroidogenic pathway.", "contents": "ACTH-induced hydrolysis of cholesteryl esters in rat adrenal cells. Rat adrenal cortical cells have been prepared by collagenase dissociation of trypsin-treated adrenal tissue. The content and compositions of cholesteryl ester, phospholipid, and triglyceride fatty acids compare favorably with those of undissociated rat adrenal tissue. During 2-hour control incubations of adrenal cortical cells, steroidogenesis was not detected, and the levels of sterol ester, phospholipid, and triglyceride fatty acids were not significantly altered. Incubations with adrenocorticotropic hormone (ACTH) resulted in coricosterone production and significant depletions of sterol ester and triglyceride fatty acids, but not of phospholipid fatty acids. Although all fatty acid esters of cholesterol were hydrolyzed under these conditions, the greatest contributions to the net decrease in sterol esters were by oleate, arachidonate, and adrenate. Incubations with dibutyryl cyclic adenosine monophosphate (0.5 mM) resulted in significantly greater levels of corticosterone production than did ACTH (250 muunits), but the effects on cellular lipids were comparable to those seen with the tropic hormone. This study represents the first demonstration of hormone-induced hydrolysis of sterol esters in an in vitro cell suspension system. The results are discussed with respect to hormone-sensitive sterol ester hydrolase of adrenal cortex, and to the role of endogenous cholesteryl esters in the steroidogenic pathway."}
{"id": "PMID:209113", "title": "Direct measurement of apoprotein B specific activity in 125I-labeled lipoproteins.", "content": "A method for determining apoprotein B specific activity in radioiodinated lipoproteins is described and validated. It utilizes organic solvents and tetramethylurea in the isolation of apoprotein B from other radiolabeled contaminants, both lipid and protein, in exogenously labeled VLDL. The contaminants are also removed from those lipoprotein classes subsequently derived from VLDL, namely IDL and LDL. The procedure requires approximately 50 microgram of apoB per analysis, allowing specific activity determinations in triplicate on 3-ml plasma samples with a standard error of less than 6%. Finally, data from a study of apoprotein B turnover in VLDL, IDL, and LDL in a human subject is presented to demonstrate the potential of this method in further elucidating the kinetic interrelationships between these lipoprotein classes.", "contents": "Direct measurement of apoprotein B specific activity in 125I-labeled lipoproteins. A method for determining apoprotein B specific activity in radioiodinated lipoproteins is described and validated. It utilizes organic solvents and tetramethylurea in the isolation of apoprotein B from other radiolabeled contaminants, both lipid and protein, in exogenously labeled VLDL. The contaminants are also removed from those lipoprotein classes subsequently derived from VLDL, namely IDL and LDL. The procedure requires approximately 50 microgram of apoB per analysis, allowing specific activity determinations in triplicate on 3-ml plasma samples with a standard error of less than 6%. Finally, data from a study of apoprotein B turnover in VLDL, IDL, and LDL in a human subject is presented to demonstrate the potential of this method in further elucidating the kinetic interrelationships between these lipoprotein classes."}
{"id": "PMID:209114", "title": "Relationship between the tissue level of cyclic AMP and the fat cell size of human adipose tissue.", "content": "The relationship between mean fat cell size, maximal tissue cyclic AMP concentration, and glycerol release was investigated in human subcutaneous adipose tissue incubated in vitro with or without isoprenaline or noradrenaline added at maximal effective concentrations. Basal and stimulated glycerol release and cyclic AMP concentration were each related to the fat cell size. Whether or not the phosphodiesterase inhibitor theophylline was present in the incubation system, basal and noradrenaline-induced cyclic AMP levels were significantly correlated with the fat cell size. The noradrenaline-induced cyclic AMP levels resulted in twice as rapid glycerol release as could be expected from the basal ratio between glycerol release and cyclic AMP. Furthermore, both basal and noradrenaline-induced glycerol release in relation to the cyclic AMP levels were more rapid in enlarge fat cells. It is concluded that basal and catecholamine-induced production of cyclic AMP is related to the fat cell size and that a quantitative relationship exists between rate of lipolysis and maximal tissue levels of cyclic AMP in human adipose tissue. Basal and noradrenaline-induced lipolysis are probably regulated by different mechanisms and the lipolytic sensitivity to cyclic AMP seems increased in large fat cells.", "contents": "Relationship between the tissue level of cyclic AMP and the fat cell size of human adipose tissue. The relationship between mean fat cell size, maximal tissue cyclic AMP concentration, and glycerol release was investigated in human subcutaneous adipose tissue incubated in vitro with or without isoprenaline or noradrenaline added at maximal effective concentrations. Basal and stimulated glycerol release and cyclic AMP concentration were each related to the fat cell size. Whether or not the phosphodiesterase inhibitor theophylline was present in the incubation system, basal and noradrenaline-induced cyclic AMP levels were significantly correlated with the fat cell size. The noradrenaline-induced cyclic AMP levels resulted in twice as rapid glycerol release as could be expected from the basal ratio between glycerol release and cyclic AMP. Furthermore, both basal and noradrenaline-induced glycerol release in relation to the cyclic AMP levels were more rapid in enlarge fat cells. It is concluded that basal and catecholamine-induced production of cyclic AMP is related to the fat cell size and that a quantitative relationship exists between rate of lipolysis and maximal tissue levels of cyclic AMP in human adipose tissue. Basal and noradrenaline-induced lipolysis are probably regulated by different mechanisms and the lipolytic sensitivity to cyclic AMP seems increased in large fat cells."}
{"id": "PMID:209115", "title": "Catabolism of the apoprotein of low density lipoproteins by the isolated perfused rat liver.", "content": "Isolated rat livers were perfused for 4 hours in a recirculating system containing washed rat erythrocytes. Biologically screened, radioiodinated low density lipoproteins (1.030 < d < 1.055 g/ml) were added to the perfusate with different amounts of whole serum to supply unlabeled rat low density lipoproteins. Apolipoprotein B contained 90% of the bound (131)I, other apolipoproteins contained 4%, and lipids contained the remainder. 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 fractional catabolic rate ranged from 0.3 to 1.7%/hr in seven experiments and was inversely related to the size of perfusate pool of low density apolipoprotein. The catabolic rate of low density apolipoprotein (fractional catabolic rate x pool size) in four livers, in which the concentration of rat low density lipoproteins was 50-100% of that present in intact rats, was 5.3 +/- 2.7 micro g hr(-1) (mean +/- SD). Similar results were obtained with human low density lipoproteins. These rates were compared with catabolic rates for the apoprotein of rat low density lipoproteins in intact animals. Fractional catabolic rate in vivo, obtained by multi-compartmental analysis of the disappearance curve of (131)I-labeled low density apolipoprotein from blood plasma, was 15.2 +/- 3.1% hr(-1) (mean +/- SD). Total catabolic rate in vivo (fractional catabolic rate x intravascular pool of low density apolipoprotein) was 76 +/- 14 micro g hr(-1) (mean +/- SD). The results suggest that only a small fraction of low density apolipoprotein mass in rats is degraded by the liver.", "contents": "Catabolism of the apoprotein of low density lipoproteins by the isolated perfused rat liver. Isolated rat livers were perfused for 4 hours in a recirculating system containing washed rat erythrocytes. Biologically screened, radioiodinated low density lipoproteins (1.030 < d < 1.055 g/ml) were added to the perfusate with different amounts of whole serum to supply unlabeled rat low density lipoproteins. Apolipoprotein B contained 90% of the bound (131)I, other apolipoproteins contained 4%, and lipids contained the remainder. 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 fractional catabolic rate ranged from 0.3 to 1.7%/hr in seven experiments and was inversely related to the size of perfusate pool of low density apolipoprotein. The catabolic rate of low density apolipoprotein (fractional catabolic rate x pool size) in four livers, in which the concentration of rat low density lipoproteins was 50-100% of that present in intact rats, was 5.3 +/- 2.7 micro g hr(-1) (mean +/- SD). Similar results were obtained with human low density lipoproteins. These rates were compared with catabolic rates for the apoprotein of rat low density lipoproteins in intact animals. Fractional catabolic rate in vivo, obtained by multi-compartmental analysis of the disappearance curve of (131)I-labeled low density apolipoprotein from blood plasma, was 15.2 +/- 3.1% hr(-1) (mean +/- SD). Total catabolic rate in vivo (fractional catabolic rate x intravascular pool of low density apolipoprotein) was 76 +/- 14 micro g hr(-1) (mean +/- SD). The results suggest that only a small fraction of low density apolipoprotein mass in rats is degraded by the liver."}
{"id": "PMID:209116", "title": "Uptake and degradation of high density lipoprotein: comparison of fibroblasts from normal subjects and from homozygous familial hypercholesterolemic subjects.", "content": "Fibroblasts cultured from the skin of subjects with homozygous familial hyperlipoproteinemia (HFH) internalize and degrade low density lipoproteins at a much lower rate than do fibroblasts from normal subjects. Evidence has been presented that this reflects the absence from such mutant cells of specialized binding sites with high affinity for low density lipoproteins. The specificity of this membrane defect in familial hypercholesterolemia is further supported by the present studies comparing the metabolism of low density lipoproteins (LDL) and high density lipoproteins (HDL) in normal fibroblasts and in fibroblasts from HFH patients. The surface binding (trypsin-releasable (125)I) of (125)I-labeled LDL by HFH cells was approximately 30% of that by normal cells at a concentration of 5 micro g LDL protein per ml. At the same concentration the internalization (cell-associated (125)I after trypsinization) and degradation (trichloroacetic acid-soluble non-iodide (125)I) of (125)I-labeled LDL were less than 10% of the values obtained with normal cells. In contrast, the binding of (125)I-labeled HDL to HFH cells was actually somewhat greater than that to normal cells. Despite this, the internalization and degradation of (125)I-labeled HDL by HFH cells averaged only 70% of that by normal cells. [(3)H]- or [(14)C]Sucrose uptake, a measure of fluid uptake by pinocytosis, was similar in normal and HFH fibroblasts. These findings are consistent with the proposal that fibroblasts from subjects with HFH lack high-affinity receptors for LDL. These receptors do not play a significant role in HDL binding and uptake. Instead, as previously proposed, HDL appears to bind randomly on the cell surface and its internalization is not facilitated by the specific mechanism that internalizes LDL. The small but significant abnormalities in HDL binding and internalization, however, suggest that there may be additional primary or secondary abnormalities of membrane structure and function in HFH cells. Finally, the observed overall rate of uptake of LDL (that internalized plus that degraded) by HFH fibroblasts was considerably greater than that expected from fluid endocytosis alone. This implies that adsorptive endocytosis, associated with binding to low-affinity sites on the cell surface, may play a significant role in LDL degradation by HFH cells, even though it does not regulate endogenous cholesterol synthesis in these cells.", "contents": "Uptake and degradation of high density lipoprotein: comparison of fibroblasts from normal subjects and from homozygous familial hypercholesterolemic subjects. Fibroblasts cultured from the skin of subjects with homozygous familial hyperlipoproteinemia (HFH) internalize and degrade low density lipoproteins at a much lower rate than do fibroblasts from normal subjects. Evidence has been presented that this reflects the absence from such mutant cells of specialized binding sites with high affinity for low density lipoproteins. The specificity of this membrane defect in familial hypercholesterolemia is further supported by the present studies comparing the metabolism of low density lipoproteins (LDL) and high density lipoproteins (HDL) in normal fibroblasts and in fibroblasts from HFH patients. The surface binding (trypsin-releasable (125)I) of (125)I-labeled LDL by HFH cells was approximately 30% of that by normal cells at a concentration of 5 micro g LDL protein per ml. At the same concentration the internalization (cell-associated (125)I after trypsinization) and degradation (trichloroacetic acid-soluble non-iodide (125)I) of (125)I-labeled LDL were less than 10% of the values obtained with normal cells. In contrast, the binding of (125)I-labeled HDL to HFH cells was actually somewhat greater than that to normal cells. Despite this, the internalization and degradation of (125)I-labeled HDL by HFH cells averaged only 70% of that by normal cells. [(3)H]- or [(14)C]Sucrose uptake, a measure of fluid uptake by pinocytosis, was similar in normal and HFH fibroblasts. These findings are consistent with the proposal that fibroblasts from subjects with HFH lack high-affinity receptors for LDL. These receptors do not play a significant role in HDL binding and uptake. Instead, as previously proposed, HDL appears to bind randomly on the cell surface and its internalization is not facilitated by the specific mechanism that internalizes LDL. The small but significant abnormalities in HDL binding and internalization, however, suggest that there may be additional primary or secondary abnormalities of membrane structure and function in HFH cells. Finally, the observed overall rate of uptake of LDL (that internalized plus that degraded) by HFH fibroblasts was considerably greater than that expected from fluid endocytosis alone. This implies that adsorptive endocytosis, associated with binding to low-affinity sites on the cell surface, may play a significant role in LDL degradation by HFH cells, even though it does not regulate endogenous cholesterol synthesis in these cells."}
{"id": "PMID:209117", "title": "A comparison of two methods to investigate the metabolism of human apolipoproteins A-I and and A-II.", "content": "Two methods are compared for measuring the kinetic parameters of apolipoprotein A-I and A-II metabolism in human plasma. In the first, high density lipoprotein apoproteins were radioiodinated in situ in the lipoprotein particle (endogenous apoprotein labeling) while in the second, individually labeled apolipoprotein A-I or A-II was incorporated into the particle by in vitro incubation (exogenous apoprotein labeling). The catabolic clearance rate of exogenously labeled apolipoprotein A-I was consistently faster than that of endogenous apolipoprotein A-I. Conversely, endogenously and exogenously labeled apolipoprotein A-II were catabolized at identical rates. The fractional plasma clearance rates of endogenous apolipoproteins A-I and A-II were the same.", "contents": "A comparison of two methods to investigate the metabolism of human apolipoproteins A-I and and A-II. Two methods are compared for measuring the kinetic parameters of apolipoprotein A-I and A-II metabolism in human plasma. In the first, high density lipoprotein apoproteins were radioiodinated in situ in the lipoprotein particle (endogenous apoprotein labeling) while in the second, individually labeled apolipoprotein A-I or A-II was incorporated into the particle by in vitro incubation (exogenous apoprotein labeling). The catabolic clearance rate of exogenously labeled apolipoprotein A-I was consistently faster than that of endogenous apolipoprotein A-I. Conversely, endogenously and exogenously labeled apolipoprotein A-II were catabolized at identical rates. The fractional plasma clearance rates of endogenous apolipoproteins A-I and A-II were the same."}
{"id": "PMID:209118", "title": "A study of the effect of environmental CO2 on experimental Wilm's tumor.", "content": "The effects of exposure of experimental murine Wilm's tumor to increased atmospheric concentrations of carbon dioxide were studied. Local tumor growth was not affected by concentrations of 76% and 55% of carbon dioxide applied for 10 and 30 minutes. There was no difference in survival of animals and weight of the tumor between the control and the experimental groups. Ten per cent of the animals treated with concentrations of 55% and 76% carbon dioxide developed metastases in contrast to 30% of metastatic growth detected in the control group. This observation, although without statistically significant difference, may lead toward further study of the carbon dioxide effect in different tumor models. Additional tumor models and different animals species will be studied.", "contents": "A study of the effect of environmental CO2 on experimental Wilm's tumor. The effects of exposure of experimental murine Wilm's tumor to increased atmospheric concentrations of carbon dioxide were studied. Local tumor growth was not affected by concentrations of 76% and 55% of carbon dioxide applied for 10 and 30 minutes. There was no difference in survival of animals and weight of the tumor between the control and the experimental groups. Ten per cent of the animals treated with concentrations of 55% and 76% carbon dioxide developed metastases in contrast to 30% of metastatic growth detected in the control group. This observation, although without statistically significant difference, may lead toward further study of the carbon dioxide effect in different tumor models. Additional tumor models and different animals species will be studied."}
{"id": "PMID:209119", "title": "Stimulation of erythropoiesis in mice by adenosine 3',5'-monophosphate and prostaglandin E1.", "content": "Adenosine 3',5'-monophosphate, 2 to 16 mg, and prostaglandin E1, 0.05 to 0.10 mg, stimulate erythropoiesis in ex-hypoxic, polycythemic mice. The stimulation can be prevented by the simultaneous administration of an antiserum to erythropoietin. India ink penetration shows that at these doses blood circulation is blocked in the kidney. Tissue hypoxia, especially in the kidney, causes production of erythropietin. The strong effect on the kidney circulation suggests that the major part of the stimulation of erythropoiesis by these agents is through their effect on renal circulation.", "contents": "Stimulation of erythropoiesis in mice by adenosine 3',5'-monophosphate and prostaglandin E1. Adenosine 3',5'-monophosphate, 2 to 16 mg, and prostaglandin E1, 0.05 to 0.10 mg, stimulate erythropoiesis in ex-hypoxic, polycythemic mice. The stimulation can be prevented by the simultaneous administration of an antiserum to erythropoietin. India ink penetration shows that at these doses blood circulation is blocked in the kidney. Tissue hypoxia, especially in the kidney, causes production of erythropietin. The strong effect on the kidney circulation suggests that the major part of the stimulation of erythropoiesis by these agents is through their effect on renal circulation."}
{"id": "PMID:209120", "title": "Sources of variation in the output of locust spiracular motoneurones receiving common synaptic driving.", "content": "1. The closer muscles of the left and the right spiracles of a thoracic segment are both innervated by two motoneurones, which spike in a variety of patterns during expiration. This paper seeks to explain the origin of these patterns. 2. No direct coupling between the two motoneurones is revealed. In an isolated thoracic ganglion both motoneurones spike at different frequencies with no tendency for their spikes to become synchronized. 3. The two closer motoneurones in one segment receive common, patterned depolarizing synaptic potentials during expiration caused by interneurones relaying information from the metathoracic ganglion. 4. The closer motoneurones of all the thoracic segments receive the same pattern of synaptic potentials from these interneurones. Despite this, the spiracles of one segment may remain shut while those on other segments continue to open and close rhythmically. 5. The interplay between common synaptic driving, the threshold of the motoneurones for spike initiation, and the tendency for a motoneurone to spike at a particular frequency even in the absence of interneuronal driving, explains the various patterns of spikes during expiration. Common synaptic driving imposes the same basic pattern of commands on all the motoneurones, but the individual motoneurones determine the final pattern of motor spikes. 6. To be effective in producing a patterned output, an input pattern must operate within narrow limits on either side of the threshold of the motoneurone. If the depolarization is too large, a high frequency of unpatterned spikes will result; if too small, then either there will be no output or a low frequency of spikes will result whose patterning will be affected by other inputs.", "contents": "Sources of variation in the output of locust spiracular motoneurones receiving common synaptic driving. 1. The closer muscles of the left and the right spiracles of a thoracic segment are both innervated by two motoneurones, which spike in a variety of patterns during expiration. This paper seeks to explain the origin of these patterns. 2. No direct coupling between the two motoneurones is revealed. In an isolated thoracic ganglion both motoneurones spike at different frequencies with no tendency for their spikes to become synchronized. 3. The two closer motoneurones in one segment receive common, patterned depolarizing synaptic potentials during expiration caused by interneurones relaying information from the metathoracic ganglion. 4. The closer motoneurones of all the thoracic segments receive the same pattern of synaptic potentials from these interneurones. Despite this, the spiracles of one segment may remain shut while those on other segments continue to open and close rhythmically. 5. The interplay between common synaptic driving, the threshold of the motoneurones for spike initiation, and the tendency for a motoneurone to spike at a particular frequency even in the absence of interneuronal driving, explains the various patterns of spikes during expiration. Common synaptic driving imposes the same basic pattern of commands on all the motoneurones, but the individual motoneurones determine the final pattern of motor spikes. 6. To be effective in producing a patterned output, an input pattern must operate within narrow limits on either side of the threshold of the motoneurone. If the depolarization is too large, a high frequency of unpatterned spikes will result; if too small, then either there will be no output or a low frequency of spikes will result whose patterning will be affected by other inputs."}
{"id": "PMID:209121", "title": "Effects of epinephrine on branchial non-electrolyte permeability in rainbow trout.", "content": "Using isolated heads perfused at constant pressure, at rates close to those occurring in vivo, the permeability of the gills of the trout Salmo gairdneri to a range of solutes was measured. Under epinephrine-free conditions, butanol and water showed similar high branchial permeability coefficients. Urea, inulin and dextrans (mol. wt 3000 and 20 000) were 7-12 times less permeant, and mannitol 60-70 times less permeant than water or butanol. Epinephrine, at 10(-6) M, greatly increased the permeability of the gills to the small hydrophilic molecules, water and urea, and to the lipophilic substance, butanol, but did not affect the penetration of the large hydrophilic solutes, mannitol, inulin and dextrans. In the presence of 10(-6) M propanolol, a beta-blocker, epinephrine had no effect on the permeation of any of the test substances except that the permeability to urea decreased somewhat. The results suggest that epinephrine increases the permeability of the membranes of the branchial cells but does not affect the permeation of substances that cross the gill walls by paracellular routes or via an intracellular 'bulk-transport' mechanism. Such an action would be expected to increase the branchial transfer of oxygen.", "contents": "Effects of epinephrine on branchial non-electrolyte permeability in rainbow trout. Using isolated heads perfused at constant pressure, at rates close to those occurring in vivo, the permeability of the gills of the trout Salmo gairdneri to a range of solutes was measured. Under epinephrine-free conditions, butanol and water showed similar high branchial permeability coefficients. Urea, inulin and dextrans (mol. wt 3000 and 20 000) were 7-12 times less permeant, and mannitol 60-70 times less permeant than water or butanol. Epinephrine, at 10(-6) M, greatly increased the permeability of the gills to the small hydrophilic molecules, water and urea, and to the lipophilic substance, butanol, but did not affect the penetration of the large hydrophilic solutes, mannitol, inulin and dextrans. In the presence of 10(-6) M propanolol, a beta-blocker, epinephrine had no effect on the permeation of any of the test substances except that the permeability to urea decreased somewhat. The results suggest that epinephrine increases the permeability of the membranes of the branchial cells but does not affect the permeation of substances that cross the gill walls by paracellular routes or via an intracellular 'bulk-transport' mechanism. Such an action would be expected to increase the branchial transfer of oxygen."}
{"id": "PMID:209122", "title": "Increased superoxide anion production by immunologically activated and chemically elicited macrophages.", "content": "We studied the capacity of cultured mouse peritoneal macrophages to generate superoxide anion (O(2-)), the initial product of conversion of oxygen to microbicidal species, during phagocytosis of opsonized zymosan or upon contact with the membrane-active agent phorbel myristate acetate (PMA). Macrophages from mice infected with Bacille Calmette-Guerin (BCG) or injected intraperitoneally with thioglycollate broth or endotoxin, released up to 12 times more O(2-) than did resident peritoneal macrophages, depending upon the cell type and whether the stimulus was zymosan or PMA. There was little if any O(2-) release from resting (unstimulated) macrophages. The density of cells on culture dishes was an important variable since crowding of the dish markedly reduced the efficiency of O(2-) production. The enhanced O(2-) release of chemically elicited and infection-activated macrophages was noted after stimulation with a wide range of concentrations of PMA and zymosan, at all time points studied (up to 120 min), and with cells maintained for 140 rain to 16 days in culture. The O(2-) response of resident cells improved twofold to zymosan and ninefold to PMA during the first 3 days in culture. The capacity to release O~ appears to be limited to actively phagocytic cell types: murine macrophage-like tumor lines and cultured human monocytes released O(2-) when stimulated by PMA or zymosan, fibroblast and endothelial lines and embryo-derived cells did not. Activity of superoxide dismutase, which removes O(2-), was not detectable in culture supernates of any cell type, and thus, differences in detectable O(2-) could not be attributed to variations in the release of this enzyme. We conclude that the phagocytosis- associated respiratory burst is significantly enhanced in mononuclear phagocytes obtained ai~r chemical inflammation or BCG infection. Increased capacity to generate O(2-) and other oxygen radicals during phagocytosis could contribute to the improved microbicidal and tumoricidal activity of activated macrophages.", "contents": "Increased superoxide anion production by immunologically activated and chemically elicited macrophages. We studied the capacity of cultured mouse peritoneal macrophages to generate superoxide anion (O(2-)), the initial product of conversion of oxygen to microbicidal species, during phagocytosis of opsonized zymosan or upon contact with the membrane-active agent phorbel myristate acetate (PMA). Macrophages from mice infected with Bacille Calmette-Guerin (BCG) or injected intraperitoneally with thioglycollate broth or endotoxin, released up to 12 times more O(2-) than did resident peritoneal macrophages, depending upon the cell type and whether the stimulus was zymosan or PMA. There was little if any O(2-) release from resting (unstimulated) macrophages. The density of cells on culture dishes was an important variable since crowding of the dish markedly reduced the efficiency of O(2-) production. The enhanced O(2-) release of chemically elicited and infection-activated macrophages was noted after stimulation with a wide range of concentrations of PMA and zymosan, at all time points studied (up to 120 min), and with cells maintained for 140 rain to 16 days in culture. The O(2-) response of resident cells improved twofold to zymosan and ninefold to PMA during the first 3 days in culture. The capacity to release O~ appears to be limited to actively phagocytic cell types: murine macrophage-like tumor lines and cultured human monocytes released O(2-) when stimulated by PMA or zymosan, fibroblast and endothelial lines and embryo-derived cells did not. Activity of superoxide dismutase, which removes O(2-), was not detectable in culture supernates of any cell type, and thus, differences in detectable O(2-) could not be attributed to variations in the release of this enzyme. We conclude that the phagocytosis- associated respiratory burst is significantly enhanced in mononuclear phagocytes obtained ai~r chemical inflammation or BCG infection. Increased capacity to generate O(2-) and other oxygen radicals during phagocytosis could contribute to the improved microbicidal and tumoricidal activity of activated macrophages."}
{"id": "PMID:209123", "title": "Restricted expression of ecotropic virus by thymocytes of leukemia-resistant (AKR X NZB)F1 mice.", "content": "AKR mice, which produce high titers of ecotropic virus, were crossed with NZB mice, which produce titers of xenotropic virus. Spleen, marrow, and lymph node cells of the F1 hybrid produced high titers of ecotropic and xenotropic viruses. However, expression of ecotropic virus by both thymus cells and peripheral T cells of the F1 was severely restricted. Despite simultaneous expression of ecotorpic and xenotropic viruses in F1 spleens, lymph nodes, and marrows evidence for recombinant viruses was not found. Such viruses were also undetectable in the F1 thymuses. The results indicate that a cellular mechanism, present in AKR thymus but lacking in the F1 influences virus expression and the formation of recombinant viruses. This may account for the low incidence of leukemia in the F1 hybrid.", "contents": "Restricted expression of ecotropic virus by thymocytes of leukemia-resistant (AKR X NZB)F1 mice. AKR mice, which produce high titers of ecotropic virus, were crossed with NZB mice, which produce titers of xenotropic virus. Spleen, marrow, and lymph node cells of the F1 hybrid produced high titers of ecotropic and xenotropic viruses. However, expression of ecotropic virus by both thymus cells and peripheral T cells of the F1 was severely restricted. Despite simultaneous expression of ecotorpic and xenotropic viruses in F1 spleens, lymph nodes, and marrows evidence for recombinant viruses was not found. Such viruses were also undetectable in the F1 thymuses. The results indicate that a cellular mechanism, present in AKR thymus but lacking in the F1 influences virus expression and the formation of recombinant viruses. This may account for the low incidence of leukemia in the F1 hybrid."}
{"id": "PMID:209124", "title": "Virus-induced atherosclerosis.", "content": "Of four groups of chickens, two (groups I and II) were infected with MDV and two were not (groups III and IV). Groups I and III were fed diets low in lipid, and groups II and IV were fed cholesterol-supplemented diets. Striking grossly visible atherosclerotic lesions were seen in large coronary arteries, aortas, and major aortic branches of infected normocholesterolemic and hypercholesterolemic chickens (groups I and II). In contrast, grossly visible atherosclerotic lesions were not seen in uninfected normocholesterolemic chickens (group III), nor in uninfected hypercholesterolemic chickens (group IV). Microscopically, arterial changes in the infected animals were characterized by occlusive fibromuscular intimal thickening which formed fibrous caps overlying areas of atheromatous change. This change closely resembled chronic atherosclerosis in man. These results may have important bearing on our understanding of the etiology and pathogenesis of human arteriosclerosis since there is widespread and persistent infection of human populations with up to five different herpes-viruses.", "contents": "Virus-induced atherosclerosis. Of four groups of chickens, two (groups I and II) were infected with MDV and two were not (groups III and IV). Groups I and III were fed diets low in lipid, and groups II and IV were fed cholesterol-supplemented diets. Striking grossly visible atherosclerotic lesions were seen in large coronary arteries, aortas, and major aortic branches of infected normocholesterolemic and hypercholesterolemic chickens (groups I and II). In contrast, grossly visible atherosclerotic lesions were not seen in uninfected normocholesterolemic chickens (group III), nor in uninfected hypercholesterolemic chickens (group IV). Microscopically, arterial changes in the infected animals were characterized by occlusive fibromuscular intimal thickening which formed fibrous caps overlying areas of atheromatous change. This change closely resembled chronic atherosclerosis in man. These results may have important bearing on our understanding of the etiology and pathogenesis of human arteriosclerosis since there is widespread and persistent infection of human populations with up to five different herpes-viruses."}
{"id": "PMID:209126", "title": "Patterned response to odor in single neurones of goldfish olfactory bulb: influence of odor quality and other stimulus parameters.", "content": "Responses of 75 single units in the goldfish olfactory bulb were analyzed in detail for their relationship to the time-course of the change in odor concentration during each odor stimulus. Odor stimuli were controlled for rise time, duration, and peak concentration by an apparatus developed for the purpose. This apparatus enabled aqueous odor stimuli to be interposed into a constant water stream without changes in flow rate. The time-course of the concentration change within the olfactory sac was inferred from conductivity measurements at the incurrent and excurrent nostrils. Temporal patterns of firing rate elicited by stimuli with relatively slow rising and falling phases could be quite complex combinations of excitation and suppression. Different temporal patterns were produced by different substances at a single concentration in most units. Statistical measures of the temporal pattern of response for a small number of cells at a given concentration were more characteristic of the stimulus substance than any of three measures of magnitude of response. The temporal patterns change when the peak concentration, duration, and rise time of the stimuli are varied. The nature of these changes suggests that the different patterns are due primarily to the combined influence of two factors: (a) a stimulus whose concentration varies over time and (b) a relationship between concentration and impulse frequency which varies from unit to unit. Some units produce patterns suggestive of influence by neural events of long time constant. The importance of temporal patterns in odor quality and odor intensity coding is discussed.", "contents": "Patterned response to odor in single neurones of goldfish olfactory bulb: influence of odor quality and other stimulus parameters. Responses of 75 single units in the goldfish olfactory bulb were analyzed in detail for their relationship to the time-course of the change in odor concentration during each odor stimulus. Odor stimuli were controlled for rise time, duration, and peak concentration by an apparatus developed for the purpose. This apparatus enabled aqueous odor stimuli to be interposed into a constant water stream without changes in flow rate. The time-course of the concentration change within the olfactory sac was inferred from conductivity measurements at the incurrent and excurrent nostrils. Temporal patterns of firing rate elicited by stimuli with relatively slow rising and falling phases could be quite complex combinations of excitation and suppression. Different temporal patterns were produced by different substances at a single concentration in most units. Statistical measures of the temporal pattern of response for a small number of cells at a given concentration were more characteristic of the stimulus substance than any of three measures of magnitude of response. The temporal patterns change when the peak concentration, duration, and rise time of the stimuli are varied. The nature of these changes suggests that the different patterns are due primarily to the combined influence of two factors: (a) a stimulus whose concentration varies over time and (b) a relationship between concentration and impulse frequency which varies from unit to unit. Some units produce patterns suggestive of influence by neural events of long time constant. The importance of temporal patterns in odor quality and odor intensity coding is discussed."}
{"id": "PMID:209127", "title": "Enhanced parainfluenza I (6/94) virus detection in latently infected human brain cell cultures by treatment with cytochalasin D and dimethyl sulfoxide.", "content": "The ability of cytochalasin D (CD) and dimethyl sulfoxide (DMSO) to enhance parainfluenza I (6/94) virus replication was studied in various cell culture systems. Treatment of CV1 cells with CD (1 microgram/ml) dissolved in DMSO prior to primary 6/94 virus exposure at 10(0)--10(5) multiplicities of infection did not substantially enhance virus replication. However, there was a transient increase in cell associated virus one day after infection of DMSO-treated cultures. CD treatment of cultures of human brain cells latently infected with 6/94 virus (LIHB cells) did not enhance 6/94 virus detection. Cocultivation of CV1 cells with CD-treated LIHB cell cultures, and cocultivation of LIHB cell cultures with CD-treated CV1 cells, resulted in the production of both cell-associated and cell-free 6/94 virus three and five days after cocultivation. No virus was detected after similar cocultivation of untreated LIHB cell cultures with untreated CV1 cells. The usefulness of CD-DMSO treatment in the rescue of virus from 6/94 LIHB cell cultures appears limited to a cocultivation system. The use of these techniques to enhance virus rescue from human tissues suspected of harboring latent viral genomes is discussed.", "contents": "Enhanced parainfluenza I (6/94) virus detection in latently infected human brain cell cultures by treatment with cytochalasin D and dimethyl sulfoxide. The ability of cytochalasin D (CD) and dimethyl sulfoxide (DMSO) to enhance parainfluenza I (6/94) virus replication was studied in various cell culture systems. Treatment of CV1 cells with CD (1 microgram/ml) dissolved in DMSO prior to primary 6/94 virus exposure at 10(0)--10(5) multiplicities of infection did not substantially enhance virus replication. However, there was a transient increase in cell associated virus one day after infection of DMSO-treated cultures. CD treatment of cultures of human brain cells latently infected with 6/94 virus (LIHB cells) did not enhance 6/94 virus detection. Cocultivation of CV1 cells with CD-treated LIHB cell cultures, and cocultivation of LIHB cell cultures with CD-treated CV1 cells, resulted in the production of both cell-associated and cell-free 6/94 virus three and five days after cocultivation. No virus was detected after similar cocultivation of untreated LIHB cell cultures with untreated CV1 cells. The usefulness of CD-DMSO treatment in the rescue of virus from 6/94 LIHB cell cultures appears limited to a cocultivation system. The use of these techniques to enhance virus rescue from human tissues suspected of harboring latent viral genomes is discussed."}
{"id": "PMID:209129", "title": "In vivo responses of paired giant mechanoreceptor neurons in Aplysia abdominal ganglion.", "content": "Two neurons with cell bodies symmetrically located in the abdominal ganglion and giant axons in the left (L1) and right (R1) pleurovisceral connectives of Aplysia californica were examined in vivo and in vitro. Direct stimulation of R1 and L1 in the intact animal does not elicit any observable behavior, suggesting that they are neither motoneurons nor command neurons. These cells respond in vivo to sudden onset mechanical stimulation of widespread regions of the body. R1 and L1 spikes are initiated in at least three different loci: (1) the peripheral axon in the foot, (2) the neuropil of the pleural and/or pedal ganglion, and (3) the neuropil of the abdominal ganglion. Furthermore, R1 and L1 probably have two different mechanisms for spike initiation: (1) sensory (foot), and (2) synaptic (abdominal and/or head ganglia). The different loci for spike initiation account for the bidirectional conduction of R1 and L1 spikes. As sensory (mechanoreceptor) neurons, R1 and L1 have peripheral axons in the ipsilateral posterior pedal nerve, show low threshold responses to stimulation of the ipsilateral posterior foot, they are rapidly adapting their responses do not decrease with repetition, and they are not blocked by high Mg++/low Ca++ solutions. As synaptically-driven neurons, R1 and L1 have widespread bilateral responsiveness, their responses decrease with repetition and their inputs are blocked with high Mg++/low Ca++ solutions. These neurons integrate sensory and synaptic inputs and conduct bidirectionally, however, their output connections must be specified before their behavioral function can be understood.", "contents": "In vivo responses of paired giant mechanoreceptor neurons in Aplysia abdominal ganglion. Two neurons with cell bodies symmetrically located in the abdominal ganglion and giant axons in the left (L1) and right (R1) pleurovisceral connectives of Aplysia californica were examined in vivo and in vitro. Direct stimulation of R1 and L1 in the intact animal does not elicit any observable behavior, suggesting that they are neither motoneurons nor command neurons. These cells respond in vivo to sudden onset mechanical stimulation of widespread regions of the body. R1 and L1 spikes are initiated in at least three different loci: (1) the peripheral axon in the foot, (2) the neuropil of the pleural and/or pedal ganglion, and (3) the neuropil of the abdominal ganglion. Furthermore, R1 and L1 probably have two different mechanisms for spike initiation: (1) sensory (foot), and (2) synaptic (abdominal and/or head ganglia). The different loci for spike initiation account for the bidirectional conduction of R1 and L1 spikes. As sensory (mechanoreceptor) neurons, R1 and L1 have peripheral axons in the ipsilateral posterior pedal nerve, show low threshold responses to stimulation of the ipsilateral posterior foot, they are rapidly adapting their responses do not decrease with repetition, and they are not blocked by high Mg++/low Ca++ solutions. As synaptically-driven neurons, R1 and L1 have widespread bilateral responsiveness, their responses decrease with repetition and their inputs are blocked with high Mg++/low Ca++ solutions. These neurons integrate sensory and synaptic inputs and conduct bidirectionally, however, their output connections must be specified before their behavioral function can be understood."}
{"id": "PMID:209152", "title": "Reflex arc of the first component of the human blink reflex: a single motoneurone study.", "content": "Latency variation of consecutive responses of single orbicularis oculi motoneurones in the first component of the electrically elicited blink reflex was 2.6 times larger than that of the H reflex of the soleus muscle fibres. Some motoneurones showed bimodal latency distribution or double responses or both at an interval of about 4-5 ms. Typical first component responses were sometimes obtained by contralateral stimulation. Central conduction time in the brainstem, estimated for 15 motoneurones, was between 2.4 and 6.6 ms. It is concluded that the first component of the blink reflex is conducted through an oligosynaptic arc including one or more interneurones.", "contents": "Reflex arc of the first component of the human blink reflex: a single motoneurone study. Latency variation of consecutive responses of single orbicularis oculi motoneurones in the first component of the electrically elicited blink reflex was 2.6 times larger than that of the H reflex of the soleus muscle fibres. Some motoneurones showed bimodal latency distribution or double responses or both at an interval of about 4-5 ms. Typical first component responses were sometimes obtained by contralateral stimulation. Central conduction time in the brainstem, estimated for 15 motoneurones, was between 2.4 and 6.6 ms. It is concluded that the first component of the blink reflex is conducted through an oligosynaptic arc including one or more interneurones."}
{"id": "PMID:209153", "title": "Radiculopathy as a complication of ankylosing spondylitis.", "content": "A cauda equina syndrome in association with ankylosing spondylitis is well recorded. We report the occurrence of an upper limb radiculopathy which progressed to a cauda equina syndrome in association with ankylosing spondylitis.", "contents": "Radiculopathy as a complication of ankylosing spondylitis. A cauda equina syndrome in association with ankylosing spondylitis is well recorded. We report the occurrence of an upper limb radiculopathy which progressed to a cauda equina syndrome in association with ankylosing spondylitis."}
{"id": "PMID:209154", "title": "Surface topography of normal and neoplastic human anterior pituitary cells maintained in vitro.", "content": "Pituitary tissues were obtained from 25 patients who underwent surgery for excision of pituitary macroadenomas, selective excision of microadenomas, or removal of a normal gland for palliation of metastatic cancer. Cells thus obtained were maintained in vitro for varying intervals, fixed, and examined by light (phase contrast), microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Previous SEM reports indicate that surface topography of in vitro neoplastic cells displays features that may correlate with neoplastic behavior. Cultured normal and pituitary tumor cells did not display these surface differences, with one exception, a prolactin-secreting microadenoma. Characteristic patterns for the cell populations were identified. Certain cell types appeared in all the cultures: 1) large and small granule-containing cells; 2) flat and irregular cells; 31 spindle-shaped cells; and 4) spherical, irregularly surfaced cells. In one case of an endocrine-inactive juvenile pituitary chromophobe adenoma, unique cells were observed. Surface topography did not appear to be of predictive value in determining the neoplastic character of pituitary tumors.", "contents": "Surface topography of normal and neoplastic human anterior pituitary cells maintained in vitro. Pituitary tissues were obtained from 25 patients who underwent surgery for excision of pituitary macroadenomas, selective excision of microadenomas, or removal of a normal gland for palliation of metastatic cancer. Cells thus obtained were maintained in vitro for varying intervals, fixed, and examined by light (phase contrast), microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Previous SEM reports indicate that surface topography of in vitro neoplastic cells displays features that may correlate with neoplastic behavior. Cultured normal and pituitary tumor cells did not display these surface differences, with one exception, a prolactin-secreting microadenoma. Characteristic patterns for the cell populations were identified. Certain cell types appeared in all the cultures: 1) large and small granule-containing cells; 2) flat and irregular cells; 31 spindle-shaped cells; and 4) spherical, irregularly surfaced cells. In one case of an endocrine-inactive juvenile pituitary chromophobe adenoma, unique cells were observed. Surface topography did not appear to be of predictive value in determining the neoplastic character of pituitary tumors."}
{"id": "PMID:209155", "title": "Intraneural hematoma of the sciatic nerve. Case report.", "content": "A case of an encapsulated organizing hematoma of the sciatic nerve is reported. Hemorrhage-induced neuropathy as a complication of anticoagulant therapy, leukemia, hemophilia, and other bleeding diatheses has been frequently reported. While trauma is the most common etiology of a hemorrhagic neuropathy, actual hematoma formation beneath the epineurium is very rare.", "contents": "Intraneural hematoma of the sciatic nerve. Case report. A case of an encapsulated organizing hematoma of the sciatic nerve is reported. Hemorrhage-induced neuropathy as a complication of anticoagulant therapy, leukemia, hemophilia, and other bleeding diatheses has been frequently reported. While trauma is the most common etiology of a hemorrhagic neuropathy, actual hematoma formation beneath the epineurium is very rare."}
{"id": "PMID:209156", "title": "Studies on carbamoylphosphate synthetase in livers of rats fed a protein free diet supplemented with methionine and threonine and injected with N-acetylglutamic acid.", "content": "Supplementation of methionine and threonine to a protein free diet reduces urinary nitrogen excretion in rats, and it has been assumed that N-acetylglutamic acid may have a regulatory role in urea synthesis. The present paper reports the effect of supplementation of methionine and threonine on the levels of N-acetylglutamic acid and of carbamoylphosphate synthetase (EC 2.7.2.5) in liver. In spite of a significant decrease in urinary urea when methionine and threonine were supplemented to the protein free diet, the activity of carbamoylphosphate synthetase was not reduced. On the other hand, following injection of glutamic acid, N-acetylglutamic acid or N-acetylglutamine, the excretion of urinary urea of rats fed the protein free diet supplemented with methionine and threonine was significantly reduced whereas the level of carbamoylphosphate synthetase was the same in each group. Furthermore, the concentrations of N-acetylglutamic acid in liver of rats fed the protein free diet or the protein free diet supplemented with methionine and threonine were the same. Therefore, these results indicated that, when methionine and threonine were supplemented to the protein free diet, the changes in the levels of N-acetylglutamic acid and of carbamoylphosphate synthetase in liver does not contribute to the reduced body weight loss and urinary nitrogen excretion.", "contents": "Studies on carbamoylphosphate synthetase in livers of rats fed a protein free diet supplemented with methionine and threonine and injected with N-acetylglutamic acid. Supplementation of methionine and threonine to a protein free diet reduces urinary nitrogen excretion in rats, and it has been assumed that N-acetylglutamic acid may have a regulatory role in urea synthesis. The present paper reports the effect of supplementation of methionine and threonine on the levels of N-acetylglutamic acid and of carbamoylphosphate synthetase (EC 2.7.2.5) in liver. In spite of a significant decrease in urinary urea when methionine and threonine were supplemented to the protein free diet, the activity of carbamoylphosphate synthetase was not reduced. On the other hand, following injection of glutamic acid, N-acetylglutamic acid or N-acetylglutamine, the excretion of urinary urea of rats fed the protein free diet supplemented with methionine and threonine was significantly reduced whereas the level of carbamoylphosphate synthetase was the same in each group. Furthermore, the concentrations of N-acetylglutamic acid in liver of rats fed the protein free diet or the protein free diet supplemented with methionine and threonine were the same. Therefore, these results indicated that, when methionine and threonine were supplemented to the protein free diet, the changes in the levels of N-acetylglutamic acid and of carbamoylphosphate synthetase in liver does not contribute to the reduced body weight loss and urinary nitrogen excretion."}
{"id": "PMID:209158", "title": "Differential response of calcium transport systems in laying hens to exogenous and endogenous changes in vitamin D status.", "content": "Changes in intestinal calcium absorption, calcium deposition into egg shell, and intestinal, renal and uterine calcium-binding protein (CaBP) in laying hens were related to changes in 25 hydroxycholecalciferol-1-hydroxylase activity (1-hydroxylase), or to the supplementation of 1alpha-hydroxycholecalciferol (1alpha-OH-CC). The onset of egg production resulted in an increased kidney 1-hydroxylase activity and intestinal and uterine CaBP. Renal concentrations of CaBP remained unchanged. Intestinal calcium and phosphorus absorption, during the period of egg shell formation, and duodenal calcium-binding protein (CaBP), were higher in 1alpha-OH-CC-fed than in cholecalciferol-fed hens. Renal or uterine CaBP and calcium deposition into the egg shell did not fluctuate with the vitamin D source or concentration. 1alpha-OH-CC injection into non-laying Nicarbazinfed hens resulted in an increase in intestinal but not renal or uterine CaBP concentrations. It is suggested that (a) CaBP in various organs responded independently to the same stimuli; and (b) calcium deposition into egg shell and uterine CaBP level are not related to kidney 1-hydroxylase activity or concentration of 1,25 dihydroxycholecalciferol.", "contents": "Differential response of calcium transport systems in laying hens to exogenous and endogenous changes in vitamin D status. Changes in intestinal calcium absorption, calcium deposition into egg shell, and intestinal, renal and uterine calcium-binding protein (CaBP) in laying hens were related to changes in 25 hydroxycholecalciferol-1-hydroxylase activity (1-hydroxylase), or to the supplementation of 1alpha-hydroxycholecalciferol (1alpha-OH-CC). The onset of egg production resulted in an increased kidney 1-hydroxylase activity and intestinal and uterine CaBP. Renal concentrations of CaBP remained unchanged. Intestinal calcium and phosphorus absorption, during the period of egg shell formation, and duodenal calcium-binding protein (CaBP), were higher in 1alpha-OH-CC-fed than in cholecalciferol-fed hens. Renal or uterine CaBP and calcium deposition into the egg shell did not fluctuate with the vitamin D source or concentration. 1alpha-OH-CC injection into non-laying Nicarbazinfed hens resulted in an increase in intestinal but not renal or uterine CaBP concentrations. It is suggested that (a) CaBP in various organs responded independently to the same stimuli; and (b) calcium deposition into egg shell and uterine CaBP level are not related to kidney 1-hydroxylase activity or concentration of 1,25 dihydroxycholecalciferol."}
{"id": "PMID:209160", "title": "Hydrogen cyanide poisoning: treatment with cobalt EDTA.", "content": "Three case reports are presented of employees who suffered varying degrees of exposure to hydrogen cyanide and their subsequent clinical courses following treatment with cobalt EDTA. A review of treatment modalities for CN- toxicity is given. It is concluded that, because of the degree of patient symptomatology associated from the use of cobalt EDTA, this therapy be reserved only for patients with the most severe degress of exposure to CN(-), and that in all other cases combined sodium nitrite and sodium thiosulphate therapy should be employed.", "contents": "Hydrogen cyanide poisoning: treatment with cobalt EDTA. Three case reports are presented of employees who suffered varying degrees of exposure to hydrogen cyanide and their subsequent clinical courses following treatment with cobalt EDTA. A review of treatment modalities for CN- toxicity is given. It is concluded that, because of the degree of patient symptomatology associated from the use of cobalt EDTA, this therapy be reserved only for patients with the most severe degress of exposure to CN(-), and that in all other cases combined sodium nitrite and sodium thiosulphate therapy should be employed."}
{"id": "PMID:209161", "title": "The course of five-year survivors of cancer in childhood.", "content": "A follow-up study was made of two independent series of 1,807 and 425 children who were alive five years after diagnosis of a malignant neoplasm. Over the subsequent 20 years (5 to 24 years after initial diagnosis), actuarial survival rates for the cohorts were 83% and 79%, respectively, compared to 97% for matched control subjects in the general population (P less than 0.01). Cure was achieved in a large majority of the 5-year relapse-free survivors of cancer in this study.", "contents": "The course of five-year survivors of cancer in childhood. A follow-up study was made of two independent series of 1,807 and 425 children who were alive five years after diagnosis of a malignant neoplasm. Over the subsequent 20 years (5 to 24 years after initial diagnosis), actuarial survival rates for the cohorts were 83% and 79%, respectively, compared to 97% for matched control subjects in the general population (P less than 0.01). Cure was achieved in a large majority of the 5-year relapse-free survivors of cancer in this study."}
{"id": "PMID:209162", "title": "Premature craniosynostosis: A common complication of juvenile thyrotoxicosis.", "content": "Cranial vault suture opacification (apparent closure) and bone age were evaluated roentgenographically in ten children with thyrotoxicosis. The bone age was advanced greater than 2 SD in only one. In comparison to 96 control children of similar age, craniosynostosis was present in each of the patients with thyrotoxicosis. Children with advanced bone age, nine due to virilizing adrenal hyperplasia and three with precocious puberty, had normal radiographic patterns of cranial suture closure. Thyrotoxic premature craniosynostosis did not interfere with continued head circumference growth nor did it result in clinical or radiographic evidence of increased intracranial pressure. We conclude that premature craniosynostosis appears to be a common feature of juvenile thyrotoxicosis. Investigation of the possible long-term adverse effects of this entity on central nervous system function is advocated.", "contents": "Premature craniosynostosis: A common complication of juvenile thyrotoxicosis. Cranial vault suture opacification (apparent closure) and bone age were evaluated roentgenographically in ten children with thyrotoxicosis. The bone age was advanced greater than 2 SD in only one. In comparison to 96 control children of similar age, craniosynostosis was present in each of the patients with thyrotoxicosis. Children with advanced bone age, nine due to virilizing adrenal hyperplasia and three with precocious puberty, had normal radiographic patterns of cranial suture closure. Thyrotoxic premature craniosynostosis did not interfere with continued head circumference growth nor did it result in clinical or radiographic evidence of increased intracranial pressure. We conclude that premature craniosynostosis appears to be a common feature of juvenile thyrotoxicosis. Investigation of the possible long-term adverse effects of this entity on central nervous system function is advocated."}
{"id": "PMID:209163", "title": "Congenital lipodystrophy: An endocrine study in three siblings. I. Disorders of carbohydrate metabolism.", "content": "Three siblings with congenital lipodystrophy were studied extensively for endocrine abnormalities. A severe disturbance in carbohydrate metabolism was observed. Plasma concentrations of glucagon and insulin were markedly elevated both in the basal state and in response to provocative stimuli. In addition, marked resistance to exogenous insulin and a diabetic oral glucose tolerance test were demonstrated. Lipid metabolism, GH, and ACTH secretion were normal...", "contents": "Congenital lipodystrophy: An endocrine study in three siblings. I. Disorders of carbohydrate metabolism. Three siblings with congenital lipodystrophy were studied extensively for endocrine abnormalities. A severe disturbance in carbohydrate metabolism was observed. Plasma concentrations of glucagon and insulin were markedly elevated both in the basal state and in response to provocative stimuli. In addition, marked resistance to exogenous insulin and a diabetic oral glucose tolerance test were demonstrated. Lipid metabolism, GH, and ACTH secretion were normal..."}
{"id": "PMID:209164", "title": "Experience with \"second-look\" operations in pediatric solid tumors.", "content": "\"Second-look\" operations were performed in 32 infants and children with initially unresectable or recurrent solid tumors treated with combination chemotherapy and/or irradiation. Tumors were resectable in 26 of 32 cases (81%). These procedures often yielded information affecting staging and treatment. Disease-free survival was achieved in 18 of 32 patients (56%). Mortality was related to progressive disease in seven cases and opportunistic infections due to immunosuppression in three. Four additional patients are alive with evidence of persistent tumor. Second-look procedures were beneficial in patients with Wilms' tumor previously operated upon by a flank approach and in children with bilateral tumors. These procedures were particularly useful in children with stage III localized neuroblastoma and cases of metastatic neuroblastoma that respond to chemotherapy. Second-look operations were also useful in selected cases of rhabdomyosarcoma, teratoma, and Ewing's sarcoma. These observations suggest that combination chemotherapy has increased the use of second-look operations in a variety of less favorable (e.g. initially unresectable or recurrent) pediatric solid tumors.", "contents": "Experience with \"second-look\" operations in pediatric solid tumors. \"Second-look\" operations were performed in 32 infants and children with initially unresectable or recurrent solid tumors treated with combination chemotherapy and/or irradiation. Tumors were resectable in 26 of 32 cases (81%). These procedures often yielded information affecting staging and treatment. Disease-free survival was achieved in 18 of 32 patients (56%). Mortality was related to progressive disease in seven cases and opportunistic infections due to immunosuppression in three. Four additional patients are alive with evidence of persistent tumor. Second-look procedures were beneficial in patients with Wilms' tumor previously operated upon by a flank approach and in children with bilateral tumors. These procedures were particularly useful in children with stage III localized neuroblastoma and cases of metastatic neuroblastoma that respond to chemotherapy. Second-look operations were also useful in selected cases of rhabdomyosarcoma, teratoma, and Ewing's sarcoma. These observations suggest that combination chemotherapy has increased the use of second-look operations in a variety of less favorable (e.g. initially unresectable or recurrent) pediatric solid tumors."}
{"id": "PMID:209165", "title": "Treatment strategy for nodular renal blastema and nephroblastomatosis associated with Wilms' tumor.", "content": "Nodular renal blastema and nephroblastomatosis were present in 8 of 118 patients (6.8%) with Wilms' tumor. Five of these 8 patients (63%) had bilateral Wilms' tumors. Two had hemihypertrophy. Preoperative renal angiograms were accurate in detecting these metanephric anomalies. The surgical approach consisted of removal of the most diseased kidney and biopsy for diffuse tumors and wedge resections for localized tumors for the remaining kidney. Postoperatively, radiation was administered when tumor extended outside the kidney. Chemotherapy consisted of vincristine and dactinomycin for 18 mo and adriamycin for 6 mo. This method of management resulted in tumor-free survival of these 8 patients for 1--44 mo (median 24 mo). Nodular renal blastema and nephroblastomatosis may possibly develop into Wilms' tumor. All of these three conditions respond to surgery, chemotherapy, and radiation. When a Wilms' tumor is encountered, it is better to explore and possibly biopsy the opposite kidney. There is a place for second-look laparotomy in this spectrum of congenital anomalies.", "contents": "Treatment strategy for nodular renal blastema and nephroblastomatosis associated with Wilms' tumor. Nodular renal blastema and nephroblastomatosis were present in 8 of 118 patients (6.8%) with Wilms' tumor. Five of these 8 patients (63%) had bilateral Wilms' tumors. Two had hemihypertrophy. Preoperative renal angiograms were accurate in detecting these metanephric anomalies. The surgical approach consisted of removal of the most diseased kidney and biopsy for diffuse tumors and wedge resections for localized tumors for the remaining kidney. Postoperatively, radiation was administered when tumor extended outside the kidney. Chemotherapy consisted of vincristine and dactinomycin for 18 mo and adriamycin for 6 mo. This method of management resulted in tumor-free survival of these 8 patients for 1--44 mo (median 24 mo). Nodular renal blastema and nephroblastomatosis may possibly develop into Wilms' tumor. All of these three conditions respond to surgery, chemotherapy, and radiation. When a Wilms' tumor is encountered, it is better to explore and possibly biopsy the opposite kidney. There is a place for second-look laparotomy in this spectrum of congenital anomalies."}
{"id": "PMID:209166", "title": "Tumor invasion of the upper inferior vena cava: the use of profound hypothermia and circulation arrest as a surgical adjunct.", "content": "Two children presented with abdominal tumors invading the upper inferior vena cava. To facilitate removal of the tumors, cardiopulmonary bypass with profound hypothermia and circulation arrest were utilized. This technique simplifies tumor excision and is worthwhile even in children with advanced malignant disease.", "contents": "Tumor invasion of the upper inferior vena cava: the use of profound hypothermia and circulation arrest as a surgical adjunct. Two children presented with abdominal tumors invading the upper inferior vena cava. To facilitate removal of the tumors, cardiopulmonary bypass with profound hypothermia and circulation arrest were utilized. This technique simplifies tumor excision and is worthwhile even in children with advanced malignant disease."}
{"id": "PMID:209168", "title": "The effect of guanidine on transmitter release in the ciliary ganglion of the chick.", "content": "1. The effect of guanidine hydrochloride on synaptic transmission at the chick ciliary ganglion was studied. 2. In bathing solution containing low calcium concentrations, guanidine produced a dose-dependent increase in the number of quanta released by the presynaptic action potential. No post-synaptic effects were observed. 3. Intracellular presynaptic recordings and monitoring of the presynaptic action potential post-synaptically via the coupling potential showed that the action of guanidine was independent of any alterations in the presynaptic spike.", "contents": "The effect of guanidine on transmitter release in the ciliary ganglion of the chick. 1. The effect of guanidine hydrochloride on synaptic transmission at the chick ciliary ganglion was studied. 2. In bathing solution containing low calcium concentrations, guanidine produced a dose-dependent increase in the number of quanta released by the presynaptic action potential. No post-synaptic effects were observed. 3. Intracellular presynaptic recordings and monitoring of the presynaptic action potential post-synaptically via the coupling potential showed that the action of guanidine was independent of any alterations in the presynaptic spike."}
{"id": "PMID:209169", "title": "Oxygen consumption and neonatal sleep states.", "content": "1. In thirty full-term infants in the first week of life, nursed in a constant volume, closed-circuit metabolism chamber in a neutral thermal environment (31.5-33.5 degrees C), measurements were made of oxygen consumption ( V(O2)) during periods of rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep.2. The mean V(O2) during REM sleep was 5.97 ml. kg(-1). min(-1). In NREM sleep the mean V(O2) was 5.72 ml. kg(-1). min(-1). This difference was significant (paired t test P < 0.05).3. When the direction of sleep state change was taken into account the difference in V(O2) between the two states was much less when REM sleep preceded NREM than when the change was in the opposite direction. In nineteen infants in whom the change was from REM to NREM the difference in V(O2) (6.18 and 6.03 ml. kg(-1). min(-1)) was not significant (P > 0.05). The mean difference when the sleep state change was from NREM to REM was significant (P < 0.01), the values being 5.54 and 5.81 ml. kg(-1). min(-1) respectively.4. In the NREM state, a gradual diminution of V(O2) with time was consistently found. This was not the case in REM sleep.5. In twelve infants studied in a cool environment (29 +/- 0.5 degrees C) V(O2) during REM sleep was 7.77, and during NREM sleep it was 6.58 ml. kg(-1). min(-1), (P < 0.001). Thus even the maximum difference found in a neutral thermal environment of 6.6% was significantly increased to 14.9% (P < 0.01) with mild thermal stress.6. No consistent changes in V(O2) with time were found in either REM or NREM sleep in twelve infants studied in a cool environment, in contrast to the findings in thermal neutrality", "contents": "Oxygen consumption and neonatal sleep states. 1. In thirty full-term infants in the first week of life, nursed in a constant volume, closed-circuit metabolism chamber in a neutral thermal environment (31.5-33.5 degrees C), measurements were made of oxygen consumption ( V(O2)) during periods of rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep.2. The mean V(O2) during REM sleep was 5.97 ml. kg(-1). min(-1). In NREM sleep the mean V(O2) was 5.72 ml. kg(-1). min(-1). This difference was significant (paired t test P < 0.05).3. When the direction of sleep state change was taken into account the difference in V(O2) between the two states was much less when REM sleep preceded NREM than when the change was in the opposite direction. In nineteen infants in whom the change was from REM to NREM the difference in V(O2) (6.18 and 6.03 ml. kg(-1). min(-1)) was not significant (P > 0.05). The mean difference when the sleep state change was from NREM to REM was significant (P < 0.01), the values being 5.54 and 5.81 ml. kg(-1). min(-1) respectively.4. In the NREM state, a gradual diminution of V(O2) with time was consistently found. This was not the case in REM sleep.5. In twelve infants studied in a cool environment (29 +/- 0.5 degrees C) V(O2) during REM sleep was 7.77, and during NREM sleep it was 6.58 ml. kg(-1). min(-1), (P < 0.001). Thus even the maximum difference found in a neutral thermal environment of 6.6% was significantly increased to 14.9% (P < 0.01) with mild thermal stress.6. No consistent changes in V(O2) with time were found in either REM or NREM sleep in twelve infants studied in a cool environment, in contrast to the findings in thermal neutrality"}
{"id": "PMID:209170", "title": "Quelling of spontaneous transmitter release by nerve impulses in low extracellular calcium solutions.", "content": "1. The effect of nerve stimulation on spontaneous transmitter release was studied at the frog neuromuscular synapse which was bathed in a solution containing very low extracellular calcium concentration. Conventional methods for intracellular and extracellular recording were used and the pattern of quantal liberation following the nerve stimulus was determined. 2. Stimulation of the motor nerve (at rates between 0.09 and 2Hz) caused a reduction in the frequency of the miniature e.p.p.s in comparison to the prestimulation values. 3. The mean distribution of the time of occurrence of the miniature e.p.p.s during the interstimulus period showed periodic oscillations. 4. The quelling effect of nerve stimulation on transmitter release is explained by the hypothesis that a low [Ca]o a reversed electrochemical gradient for calcium occurs and nerve stimulation causes an increased calcium conductance leading to calcium efflux which in turn temporarily reduces [Ca]i and transmitter release.", "contents": "Quelling of spontaneous transmitter release by nerve impulses in low extracellular calcium solutions. 1. The effect of nerve stimulation on spontaneous transmitter release was studied at the frog neuromuscular synapse which was bathed in a solution containing very low extracellular calcium concentration. Conventional methods for intracellular and extracellular recording were used and the pattern of quantal liberation following the nerve stimulus was determined. 2. Stimulation of the motor nerve (at rates between 0.09 and 2Hz) caused a reduction in the frequency of the miniature e.p.p.s in comparison to the prestimulation values. 3. The mean distribution of the time of occurrence of the miniature e.p.p.s during the interstimulus period showed periodic oscillations. 4. The quelling effect of nerve stimulation on transmitter release is explained by the hypothesis that a low [Ca]o a reversed electrochemical gradient for calcium occurs and nerve stimulation causes an increased calcium conductance leading to calcium efflux which in turn temporarily reduces [Ca]i and transmitter release."}
{"id": "PMID:209171", "title": "The role of calcium ions in tetanic and post-tetanic increase of miniature end-plate potential frequency.", "content": "1. The role of Ca ions in transmitter release changes, during and after high frequency stimulation of the motor nerve (10--100 Hz), was examined at the frog neuromuscular junction. 2. The stimulation-induced changes in miniature end-plate potential frequency (f) resembled the changes in end-plate potential amplitude recently described by Magleby and Zengel (1975, 1976). 3. The effects of tetanic stimulation on f under inward electrochemical gradient for Ca ions were compared with those under reversed gradient and four differences were found: (a) The increase in f during the tetanus under reversed Ca gradient conditions is much smaller than with an inward Ca gradient. (b) The increase in f under reversed Ca gradient is preceded by a small decrease in f, whereas with an inward Ca gradient an immediate increase in f is observed. (c) After the termination of the tetanus with a reversed Ca gradient, there is a further increase in f, compared to a decrease with an inward Ca gradient. (d) The augmentation phase of post-tetanic potentiation was practically abolished. 4. The experimental results are explained by assuming that high frequency nerve stimulation causes an increase in transmitter release by at least two distinct processes: influx of Ca ions through the presynaptic membrane and release of Ca ions from intracellular stores. It is suggested that Na ions couple nerve activity to intracellular release of Ca.", "contents": "The role of calcium ions in tetanic and post-tetanic increase of miniature end-plate potential frequency. 1. The role of Ca ions in transmitter release changes, during and after high frequency stimulation of the motor nerve (10--100 Hz), was examined at the frog neuromuscular junction. 2. The stimulation-induced changes in miniature end-plate potential frequency (f) resembled the changes in end-plate potential amplitude recently described by Magleby and Zengel (1975, 1976). 3. The effects of tetanic stimulation on f under inward electrochemical gradient for Ca ions were compared with those under reversed gradient and four differences were found: (a) The increase in f during the tetanus under reversed Ca gradient conditions is much smaller than with an inward Ca gradient. (b) The increase in f under reversed Ca gradient is preceded by a small decrease in f, whereas with an inward Ca gradient an immediate increase in f is observed. (c) After the termination of the tetanus with a reversed Ca gradient, there is a further increase in f, compared to a decrease with an inward Ca gradient. (d) The augmentation phase of post-tetanic potentiation was practically abolished. 4. The experimental results are explained by assuming that high frequency nerve stimulation causes an increase in transmitter release by at least two distinct processes: influx of Ca ions through the presynaptic membrane and release of Ca ions from intracellular stores. It is suggested that Na ions couple nerve activity to intracellular release of Ca."}
{"id": "PMID:209172", "title": "Clumping and oscillations in evoked transmitter release at the frog neuromuscular junction.", "content": "1. Time series analysis of evoked transmitter release was performed at the frog neuromuscular synapse. 2. Clumping of end-plate potentials with similar amplitude was found in the time domain. 3. At low quantal contents periodic oscillations were observed with a period of 14 sec. 4. Clumping and oscillations are phenomena of presynaptic origin. 5. The results are explained on the hypothesis that periodic fluctuations occur in Ca concentration inside the presynaptic nerve terminal.", "contents": "Clumping and oscillations in evoked transmitter release at the frog neuromuscular junction. 1. Time series analysis of evoked transmitter release was performed at the frog neuromuscular synapse. 2. Clumping of end-plate potentials with similar amplitude was found in the time domain. 3. At low quantal contents periodic oscillations were observed with a period of 14 sec. 4. Clumping and oscillations are phenomena of presynaptic origin. 5. The results are explained on the hypothesis that periodic fluctuations occur in Ca concentration inside the presynaptic nerve terminal."}
{"id": "PMID:209173", "title": "Oxytocin release following osmotic activation of oxytocin neurones in the paraventricular and supraoptic nuclei.", "content": "1. Recordings were made from a total of 35 antidromically identified neurones in the paraventricular (PV) and supraoptic (SO) nuclei of urethane-anaesthetized lactating rats. During recording plasma osmotic pressure was raised by 12 m-osmole/kg by injection of hypertonic solutions of NaCl, LiCl, or mannitol.2. Nine PV neurones (mean firing rate 4.2 +/- 1.0 (S.E.) spikes/sec) were classified as oxytocin cells because they gave a burst of activity before reflex milk-ejections. None of these showed a bursting (phasic) firing pattern. Ten PV neurones (mean firing rate 1.8 +/- 0.2 spikes/sec) fired phasically either before or after injection of hypertonic NaCl and were classified as vasopressin cells. The remaining six PV cells (mean firing rate 1.6 +/- 0.9 spikes/sec) showed no bursts of firing related to milk ejection and did not fire phasically.3. Increasing plasma osmotic pressure by injection of hypertonic NaCl increased the mean firing rate of PV oxytocin cells to 7.0 +/- 1.0 spikes/sec. Vasopressin cells in the PV nucleus were much less responsive and the mean firing rate after injection was 2.9 +/- 0.4 spikes/sec. The third group of PV neurones was unresponsive.4. Plasma oxytocin concentration (determined by radioimmunoassay) increased from 2.1 +/- 0.3 muu./ml. in the control period to 10.9 +/- 2.8 muu./ml. 30 min after I.P. injection of 1 ml. 1.5 M-NaCl and to 14.8 +/- 2.8 muu./ml. following injection of a second 1 ml. 1.5 M-NaCl.5. The responses of oxytocin and vasopressin neurones in the SO nucleus to an increase in plasma osmotic pressure following injections of hypertonic solutions of LiCl or mannitol were similar to those observed when plasma osmotic pressure was raised by NaCl.6. It may be concluded that both oxytocin and vasopressin cells in the neurohypophysical system are responsive to the osmotic pressure of the blood plasma rather than to Na(+) or Cl(-) concentration, that osmotic activation of oxytocin cells releases sufficient oxytocin to increase its plasma concentration, and that there may be a functional difference between the SO and PV nuclei.", "contents": "Oxytocin release following osmotic activation of oxytocin neurones in the paraventricular and supraoptic nuclei. 1. Recordings were made from a total of 35 antidromically identified neurones in the paraventricular (PV) and supraoptic (SO) nuclei of urethane-anaesthetized lactating rats. During recording plasma osmotic pressure was raised by 12 m-osmole/kg by injection of hypertonic solutions of NaCl, LiCl, or mannitol.2. Nine PV neurones (mean firing rate 4.2 +/- 1.0 (S.E.) spikes/sec) were classified as oxytocin cells because they gave a burst of activity before reflex milk-ejections. None of these showed a bursting (phasic) firing pattern. Ten PV neurones (mean firing rate 1.8 +/- 0.2 spikes/sec) fired phasically either before or after injection of hypertonic NaCl and were classified as vasopressin cells. The remaining six PV cells (mean firing rate 1.6 +/- 0.9 spikes/sec) showed no bursts of firing related to milk ejection and did not fire phasically.3. Increasing plasma osmotic pressure by injection of hypertonic NaCl increased the mean firing rate of PV oxytocin cells to 7.0 +/- 1.0 spikes/sec. Vasopressin cells in the PV nucleus were much less responsive and the mean firing rate after injection was 2.9 +/- 0.4 spikes/sec. The third group of PV neurones was unresponsive.4. Plasma oxytocin concentration (determined by radioimmunoassay) increased from 2.1 +/- 0.3 muu./ml. in the control period to 10.9 +/- 2.8 muu./ml. 30 min after I.P. injection of 1 ml. 1.5 M-NaCl and to 14.8 +/- 2.8 muu./ml. following injection of a second 1 ml. 1.5 M-NaCl.5. The responses of oxytocin and vasopressin neurones in the SO nucleus to an increase in plasma osmotic pressure following injections of hypertonic solutions of LiCl or mannitol were similar to those observed when plasma osmotic pressure was raised by NaCl.6. It may be concluded that both oxytocin and vasopressin cells in the neurohypophysical system are responsive to the osmotic pressure of the blood plasma rather than to Na(+) or Cl(-) concentration, that osmotic activation of oxytocin cells releases sufficient oxytocin to increase its plasma concentration, and that there may be a functional difference between the SO and PV nuclei."}
{"id": "PMID:209174", "title": "Control of calcium channels by membrane receptors in the rat parotid gland.", "content": "1. The mechanism of action of agonists that stimulate K release from the parotid gland was investigated by monitoring efflux of 86Rb from rat parotid slices. 2. As in previous studies, the 86Rb release was increased by agonists in a biphasic manner. An early, transient phase occurred that was independent of extracellular Ca. This was followed by a sustained (or slowly falling phase) that required extracellular Ca. 3. The agonists were investigated as to their additivity and to their sensitivity to inhibition by a number of putative Ca-antagonists. 4. When carbachol, epinephrine and Substance P were employed in supramaximal concentrations, no combination of agonists produced a summated 86Rb release response, despite the fact that the Ca concentration was submaximal. 5. The sustained phase of 86Rb release, which is dependent on extracellular Ca, was blocked by La, Ni, Co and neomycin; the transient phase was unaffected by these agents. 6. The local anaesthetics tetracaine and procaine inhibited both the transient and sustained phases of the responses to carbachol and phenylephrine; responses to Substance P and to the divalent cationophore, A23187, were largely refractory to this effect. 7. These results support the contention that, in the parotid, muscarinic, alpha-adrenergic and peptide receptors regulate the same Ca influx sites. 8. Also, these results suggest that La, Ni, Co and neomycin appear to antagonize the action of Ca by impeding inward movement of the cation through activated Ca influx sites. 9. Finally, the local anesthetics appear to inhibit, and therefore, serve to define, a transduction step between receptor occupation and channel activation. 10. In the case of the Substance P mechanism, it appears that the transduction mechanism must be qualitatively different to that for the muscarinic or alpha-adrenergic mechanisms.", "contents": "Control of calcium channels by membrane receptors in the rat parotid gland. 1. The mechanism of action of agonists that stimulate K release from the parotid gland was investigated by monitoring efflux of 86Rb from rat parotid slices. 2. As in previous studies, the 86Rb release was increased by agonists in a biphasic manner. An early, transient phase occurred that was independent of extracellular Ca. This was followed by a sustained (or slowly falling phase) that required extracellular Ca. 3. The agonists were investigated as to their additivity and to their sensitivity to inhibition by a number of putative Ca-antagonists. 4. When carbachol, epinephrine and Substance P were employed in supramaximal concentrations, no combination of agonists produced a summated 86Rb release response, despite the fact that the Ca concentration was submaximal. 5. The sustained phase of 86Rb release, which is dependent on extracellular Ca, was blocked by La, Ni, Co and neomycin; the transient phase was unaffected by these agents. 6. The local anaesthetics tetracaine and procaine inhibited both the transient and sustained phases of the responses to carbachol and phenylephrine; responses to Substance P and to the divalent cationophore, A23187, were largely refractory to this effect. 7. These results support the contention that, in the parotid, muscarinic, alpha-adrenergic and peptide receptors regulate the same Ca influx sites. 8. Also, these results suggest that La, Ni, Co and neomycin appear to antagonize the action of Ca by impeding inward movement of the cation through activated Ca influx sites. 9. Finally, the local anesthetics appear to inhibit, and therefore, serve to define, a transduction step between receptor occupation and channel activation. 10. In the case of the Substance P mechanism, it appears that the transduction mechanism must be qualitatively different to that for the muscarinic or alpha-adrenergic mechanisms."}
{"id": "PMID:209175", "title": "Temperature-sensitive aspects of evoked and spontaneous transmitter release at the frog neuromuscular junction.", "content": "1. The temperature dependence of presynaptic processes involved in neuromuscular transmission was studied by rapidly increasing the temperature of cooled frog neuromuscular junctions by 4--10 degrees C using pulses from a neodymium laser. The temperature elevation was complete within 0.5 msec, and decayed back to control levels with a time constant of about 7--8 sec. 2. Temperature jumps completed before nerve stimulation increased the quantal content and decreased the latency of the end-plate potential (e.p.p.). The Q10 for e.p.p. quantal content in low [Ca2+] Ringer averaged about 3.9 over the range 1--18 degrees C. 3. Temperature jumps occurring during the synaptic delay (the interval between the presynaptic action potential and the onset of the e.p.p.) also increased the quantal content and decreased the latency of the e.p.p. These effects diminished as the onset of the temperature jump was moved closer to the expected onset of the e.p.p. Temperature jumps applied after the onset of the e.p.p. immediately accelerated the time course of the e.p.p. but did not significantly alter quantal content. These results demonstrate that the magnitude and timing of evoked release are influenced by temperature-sensitive processes that operate both during and shortly after the presynaptic nerve action potential, but are largely complete before the onset of release. 4. Temperature jumps were applied at various times during the interval between two nerve stimuli. The amplitude of the second e.p.p. decreased as the temperature jump was moved earlier in the interstimulus interval, suggesting that the rise in temperature following the first nerve stimulus accelerates the decay of facilitation. When the temperature jump was moved from 10 msec after to 10 msec before the onset of the first e.p.p., the amplitude of the second e.p.p. either decreased or showed no change. The fact that the second e.p.p. did not increase suggests that the temperature-sensitive processes that increase the quantal content of the conditioning e.p.p. do not greatly increase the facilitation following that e.p.p. 5. Temperature jumps immediately accelerated the time course of spontaneous miniature end-plate potentials (m.e.p.p.s) and increased their frequency. Experiments using slow temperature changes revealed that the Q10 for m.e.p.p. frequency in normal Ringer is about 10 over the range 10--20 degrees C. M.e.p.p. frequency was much less sensitive to temperature changes below about 10 degrees C. When the nerve terminal was depolarized by 20 mM-K+ in the presence of Ca2+, the Q10 for the rate of spontaneous release over the range 10--20 degrees C decreased to about 4, similar to the Q10 for e.p.p. quantal content. In the absence of extracellular Ca2+ the Q10 for m.e.p.p. frequency in 20 mM-K+ remained near 10. 6. The marked difference in Q10S for spontaneous transmitter release under different experimental conditions suggests that not all transmitter release uses identical mechanisms...", "contents": "Temperature-sensitive aspects of evoked and spontaneous transmitter release at the frog neuromuscular junction. 1. The temperature dependence of presynaptic processes involved in neuromuscular transmission was studied by rapidly increasing the temperature of cooled frog neuromuscular junctions by 4--10 degrees C using pulses from a neodymium laser. The temperature elevation was complete within 0.5 msec, and decayed back to control levels with a time constant of about 7--8 sec. 2. Temperature jumps completed before nerve stimulation increased the quantal content and decreased the latency of the end-plate potential (e.p.p.). The Q10 for e.p.p. quantal content in low [Ca2+] Ringer averaged about 3.9 over the range 1--18 degrees C. 3. Temperature jumps occurring during the synaptic delay (the interval between the presynaptic action potential and the onset of the e.p.p.) also increased the quantal content and decreased the latency of the e.p.p. These effects diminished as the onset of the temperature jump was moved closer to the expected onset of the e.p.p. Temperature jumps applied after the onset of the e.p.p. immediately accelerated the time course of the e.p.p. but did not significantly alter quantal content. These results demonstrate that the magnitude and timing of evoked release are influenced by temperature-sensitive processes that operate both during and shortly after the presynaptic nerve action potential, but are largely complete before the onset of release. 4. Temperature jumps were applied at various times during the interval between two nerve stimuli. The amplitude of the second e.p.p. decreased as the temperature jump was moved earlier in the interstimulus interval, suggesting that the rise in temperature following the first nerve stimulus accelerates the decay of facilitation. When the temperature jump was moved from 10 msec after to 10 msec before the onset of the first e.p.p., the amplitude of the second e.p.p. either decreased or showed no change. The fact that the second e.p.p. did not increase suggests that the temperature-sensitive processes that increase the quantal content of the conditioning e.p.p. do not greatly increase the facilitation following that e.p.p. 5. Temperature jumps immediately accelerated the time course of spontaneous miniature end-plate potentials (m.e.p.p.s) and increased their frequency. Experiments using slow temperature changes revealed that the Q10 for m.e.p.p. frequency in normal Ringer is about 10 over the range 10--20 degrees C. M.e.p.p. frequency was much less sensitive to temperature changes below about 10 degrees C. When the nerve terminal was depolarized by 20 mM-K+ in the presence of Ca2+, the Q10 for the rate of spontaneous release over the range 10--20 degrees C decreased to about 4, similar to the Q10 for e.p.p. quantal content. In the absence of extracellular Ca2+ the Q10 for m.e.p.p. frequency in 20 mM-K+ remained near 10. 6. The marked difference in Q10S for spontaneous transmitter release under different experimental conditions suggests that not all transmitter release uses identical mechanisms..."}
{"id": "PMID:209176", "title": "Synaptic delay in the heart: an ionophoretic study.", "content": "1. Neurotransmitters were applied ionophoretically to spontaneously beating clusters of ventricular muscle cells cultured from neonatal rats. 2. Acetylcholine or its analogue carbachol produced hyperpolarization and decreased the rate of spontaneous beating. These responses had minimum latencies of about 250 msec and total durations of 6-12 sec. 3. Noradrenaline, adrenaline or isoprenaline increased the rate of spontaneous beating. The minimum latency for this effect was 3-6 sec. Following a single brief pulse the rate remained elevated for 2 min or more. 4. Chronotropic responses of intact atria from adult rats to stimulation of the autonomic nerves were of similar time course to responses of the cultured muscle cells. 5. Calculations based on the theory of diffusion showed that access of drugs to their receptors could not be rate-limiting for the observed responses, unless a diffusion barrier of rather special properties was postulated. A number of other explanations for the long latencies have been ruled out; these are most likely to be due to some physical or chemical process occurring in or under the cell membrane. 6. Attempts to mimic responses to catecholamines by intracellular application of cyclic AMP were unsuccessful, perhaps because the release of nucleotide from the pipettes was insufficient. A theoretical treatment suggests that ionophoretic efflux of anions might be greatly diminished by the opposing electro-osmotic flux.", "contents": "Synaptic delay in the heart: an ionophoretic study. 1. Neurotransmitters were applied ionophoretically to spontaneously beating clusters of ventricular muscle cells cultured from neonatal rats. 2. Acetylcholine or its analogue carbachol produced hyperpolarization and decreased the rate of spontaneous beating. These responses had minimum latencies of about 250 msec and total durations of 6-12 sec. 3. Noradrenaline, adrenaline or isoprenaline increased the rate of spontaneous beating. The minimum latency for this effect was 3-6 sec. Following a single brief pulse the rate remained elevated for 2 min or more. 4. Chronotropic responses of intact atria from adult rats to stimulation of the autonomic nerves were of similar time course to responses of the cultured muscle cells. 5. Calculations based on the theory of diffusion showed that access of drugs to their receptors could not be rate-limiting for the observed responses, unless a diffusion barrier of rather special properties was postulated. A number of other explanations for the long latencies have been ruled out; these are most likely to be due to some physical or chemical process occurring in or under the cell membrane. 6. Attempts to mimic responses to catecholamines by intracellular application of cyclic AMP were unsuccessful, perhaps because the release of nucleotide from the pipettes was insufficient. A theoretical treatment suggests that ionophoretic efflux of anions might be greatly diminished by the opposing electro-osmotic flux."}
{"id": "PMID:209177", "title": "Synaptic transmission to the horizontal cells in the retina of the larval tiger salamander.", "content": "1. The receptive field diameter for most horizontal cells far exceeds the lateral spread of processes for any cell. Therefore horizontal cells probably receive synaptic input from neighbours as well as from the photoreceptors. The electrical effects of these two synaptic inputs were studied. 2. We have characterized the electrical properties of the horizontal cell inputs by determining the current-voltage curves in dark and light. These curves were compared with those obtained in the presence of Co2+ or Mg2 was nearly identical to the curve in the light. 4. The putative transmitter substances glutamate, aspartate and GABA depolarized the cells by increasing conductance. Current-voltage curves measured in the presence of these substances intersected the dark and light curves at +50 mV, the same level at which the dark and light curves intersect. 5. The light response of cells uith broad receptive fields, between 1.0 and 2.0 mm, showed little or no change in conductance associated with the light response. The input resistance was near 20 Momega, and the current-voltage curves intersected at an extrapolated potential level near 200 mV. 6. In the presence of ACh, electrical properties of the broad field cells reverted to those of the narrow field cells: the receptive field was reduced to 0.5 mm, the imput resistance increased, and the current-voltage curves intersected near +50 mV. Thus ACh appeared to interrupt synaptic input from neighbouring horizontal cells. 7. The results confirm the suggestion that horizontal cells receive a tonic excitatory input from the photoreceptors which is decreased by light. They show that horizontal cells receive an additional input from their neighbours, not associated with a measurable conductance change. The input from neighbours is selectively interrupted by ACh, but the nature of this synapse and of the cholinergic action is not known.", "contents": "Synaptic transmission to the horizontal cells in the retina of the larval tiger salamander. 1. The receptive field diameter for most horizontal cells far exceeds the lateral spread of processes for any cell. Therefore horizontal cells probably receive synaptic input from neighbours as well as from the photoreceptors. The electrical effects of these two synaptic inputs were studied. 2. We have characterized the electrical properties of the horizontal cell inputs by determining the current-voltage curves in dark and light. These curves were compared with those obtained in the presence of Co2+ or Mg2 was nearly identical to the curve in the light. 4. The putative transmitter substances glutamate, aspartate and GABA depolarized the cells by increasing conductance. Current-voltage curves measured in the presence of these substances intersected the dark and light curves at +50 mV, the same level at which the dark and light curves intersect. 5. The light response of cells uith broad receptive fields, between 1.0 and 2.0 mm, showed little or no change in conductance associated with the light response. The input resistance was near 20 Momega, and the current-voltage curves intersected at an extrapolated potential level near 200 mV. 6. In the presence of ACh, electrical properties of the broad field cells reverted to those of the narrow field cells: the receptive field was reduced to 0.5 mm, the imput resistance increased, and the current-voltage curves intersected near +50 mV. Thus ACh appeared to interrupt synaptic input from neighbouring horizontal cells. 7. The results confirm the suggestion that horizontal cells receive a tonic excitatory input from the photoreceptors which is decreased by light. They show that horizontal cells receive an additional input from their neighbours, not associated with a measurable conductance change. The input from neighbours is selectively interrupted by ACh, but the nature of this synapse and of the cholinergic action is not known."}
{"id": "PMID:209178", "title": "Mechanisms of post-synaptic excitation in amphibian motoneurones.", "content": "1. Post-synaptic excitation produced in motoneurones of the isolated perfused frog spinal cord by different monosynaptic inputs and by ionophoretically applied glutamate was analysed with intracellular recording technique. 2. Ca2+-deficient, high Mg2+ (5--20 mM) media or addition of Mn2+ (2mM) or Co2+ (5 mM) reversibly abolished chemically mediated e.p.s.p.s derived from medullary reticular formation, ventral and lateral columns, but not the short-latency, rapidly rising e.p.s.p.s derived from dorsal roots or muscle nerves, suggesting electric coupling between some primary afferents and spinal motoneurones. This conclusion is consistent with the dynamic properties of dorsal root e.p.s.p.s, their small sensitivity to cooling, and with results of correction of intracellular records made for contribution of extracellular field potential. E.p.s.p.s evoked by ventral root stimulation were also insensitive to Ca2+-lack and presence of 5--10 mM-Mg2+. 3. As the post-synaptic membrane was made more negative the amplitude of electrotonic dorsal root e.p.s.p.s was increased, and it was decreased by depolarizing currents. No reversal of the early part of the electrotonic e.p.s.p. was observed, although the presence of the local response would account for the occasional reversal of its later phase seen with depolarization. 4. When hyperpolarizing and depolarizing currents were applied to motoneurones in which chemically mediated e.p.s.p.s of the reticular cells, the ventral and lateral columns, were evoked, the actual reversal of the early part of e.p.s.p. was not observed, and there was no correlation between the sensitivity of the e.p.s.p.s to injected currents and their time course. The positive values of the extrapolated reversal potentials and the effects of changes in ionic content of perfusing media suggest that synaptically released transmitter triggers off the Na permeability of the subsynaptic membrane. 5. The amplitude of depolarization produced by ionophoretically applied glutamate depends non-linearly on membrane potential and the curvature of this dependence differs from that seen with chemically mediated s.p.s.p.s. The asymptotic nature of this relationship is explicable by a dependence of the membrane conductance change upon the membrane voltage. 6. The results of conductance measurements during the glutamate induced depolarization, the values of apparent reversal potentials and their dependence on external Na+ and K+ and internal Cl- is explicable by the opening post-synaptic channel gates for Na+ and closing post-synaptic channel gates for K+. 7. Chemical and electrical transmission in the amphibian cord is discussed in relation to recent anatomical findings.", "contents": "Mechanisms of post-synaptic excitation in amphibian motoneurones. 1. Post-synaptic excitation produced in motoneurones of the isolated perfused frog spinal cord by different monosynaptic inputs and by ionophoretically applied glutamate was analysed with intracellular recording technique. 2. Ca2+-deficient, high Mg2+ (5--20 mM) media or addition of Mn2+ (2mM) or Co2+ (5 mM) reversibly abolished chemically mediated e.p.s.p.s derived from medullary reticular formation, ventral and lateral columns, but not the short-latency, rapidly rising e.p.s.p.s derived from dorsal roots or muscle nerves, suggesting electric coupling between some primary afferents and spinal motoneurones. This conclusion is consistent with the dynamic properties of dorsal root e.p.s.p.s, their small sensitivity to cooling, and with results of correction of intracellular records made for contribution of extracellular field potential. E.p.s.p.s evoked by ventral root stimulation were also insensitive to Ca2+-lack and presence of 5--10 mM-Mg2+. 3. As the post-synaptic membrane was made more negative the amplitude of electrotonic dorsal root e.p.s.p.s was increased, and it was decreased by depolarizing currents. No reversal of the early part of the electrotonic e.p.s.p. was observed, although the presence of the local response would account for the occasional reversal of its later phase seen with depolarization. 4. When hyperpolarizing and depolarizing currents were applied to motoneurones in which chemically mediated e.p.s.p.s of the reticular cells, the ventral and lateral columns, were evoked, the actual reversal of the early part of e.p.s.p. was not observed, and there was no correlation between the sensitivity of the e.p.s.p.s to injected currents and their time course. The positive values of the extrapolated reversal potentials and the effects of changes in ionic content of perfusing media suggest that synaptically released transmitter triggers off the Na permeability of the subsynaptic membrane. 5. The amplitude of depolarization produced by ionophoretically applied glutamate depends non-linearly on membrane potential and the curvature of this dependence differs from that seen with chemically mediated s.p.s.p.s. The asymptotic nature of this relationship is explicable by a dependence of the membrane conductance change upon the membrane voltage. 6. The results of conductance measurements during the glutamate induced depolarization, the values of apparent reversal potentials and their dependence on external Na+ and K+ and internal Cl- is explicable by the opening post-synaptic channel gates for Na+ and closing post-synaptic channel gates for K+. 7. Chemical and electrical transmission in the amphibian cord is discussed in relation to recent anatomical findings."}
{"id": "PMID:209179", "title": "Competitive antagonism by phentolamine of responses to biogenic amines and the transmitter at a neuroglandular junction.", "content": "1. A quantitative study has been made of phentolamine's inhibition of the electrical and secretory responses of the isolated salivary glands of Nauphoeta cinerea Olivier to nerve stimulation and bath applications of agonists. 2. The results suggested that phentolamine is a competitive antagonist having an affinity constant of about 1 micrometer-1 for the receptors for dopamine, noradrenaline, adrenaline and the neurotransmitter. 3. Phentolamine also inhibited responses to 5-hydroxytryptamine in a manner seemingly more complex than competitive antagonism. Attempts to estimate the affinity constant gave values of about 0.08 and 0.015 microgram-1 for inhibition of the secretory and electrical responses respectively. 4. This investigation showed that phentolamine discriminates between two kinds of receptor in this gland, one binding 5-hydroxytryptamine and the other combining with catecholamines and the neurotransmitter.", "contents": "Competitive antagonism by phentolamine of responses to biogenic amines and the transmitter at a neuroglandular junction. 1. A quantitative study has been made of phentolamine's inhibition of the electrical and secretory responses of the isolated salivary glands of Nauphoeta cinerea Olivier to nerve stimulation and bath applications of agonists. 2. The results suggested that phentolamine is a competitive antagonist having an affinity constant of about 1 micrometer-1 for the receptors for dopamine, noradrenaline, adrenaline and the neurotransmitter. 3. Phentolamine also inhibited responses to 5-hydroxytryptamine in a manner seemingly more complex than competitive antagonism. Attempts to estimate the affinity constant gave values of about 0.08 and 0.015 microgram-1 for inhibition of the secretory and electrical responses respectively. 4. This investigation showed that phentolamine discriminates between two kinds of receptor in this gland, one binding 5-hydroxytryptamine and the other combining with catecholamines and the neurotransmitter."}
{"id": "PMID:209180", "title": "Light-activated hydrolysis of GTP and cyclic GMP in the rod outer segments.", "content": "1. The hydrolysis of guanosine triphosphate (GTP) and the consequent formation of guanosine diphosphate (GDP) and phosphate (P1) are activated by light in a suspension of broken retinal rods: the hydrolysis rate with GTP in the micrometer concentration range is 2.5-3.5 n-mole/min per mg of rhodopsin in the preparation. 2. The ionic composition of the medium suspending the rods is not critical: the hydrolysis is present in NaCl saline solution with MG2+ as well as in Tris-HC1 buffer solution, and with the chelating agent EDTA. 3. The ionic strength is critical: the effect is reduced when the broken rods are suspended in a low salt mannitol solution, and is altogether abolished when they are separated from the mannitol solution; it reappears when the mannitol solution is added again in the presence of salts. An element essential for the effect is thus reversibly released in the mannitol solution. No hydrolytic activity on GTP, however, is found in the mannitol soluble fraction. 4. The cyclic nucleotide phosphodiesterase is eluted from the rods in the mannitol solution, and is reaggregated to the rods in the presence of salts; once recombined with the rods, it can be activated by light. 5. The activation of the phosphodiesterase by light is present in the absence of added nucleotide triphosphates.", "contents": "Light-activated hydrolysis of GTP and cyclic GMP in the rod outer segments. 1. The hydrolysis of guanosine triphosphate (GTP) and the consequent formation of guanosine diphosphate (GDP) and phosphate (P1) are activated by light in a suspension of broken retinal rods: the hydrolysis rate with GTP in the micrometer concentration range is 2.5-3.5 n-mole/min per mg of rhodopsin in the preparation. 2. The ionic composition of the medium suspending the rods is not critical: the hydrolysis is present in NaCl saline solution with MG2+ as well as in Tris-HC1 buffer solution, and with the chelating agent EDTA. 3. The ionic strength is critical: the effect is reduced when the broken rods are suspended in a low salt mannitol solution, and is altogether abolished when they are separated from the mannitol solution; it reappears when the mannitol solution is added again in the presence of salts. An element essential for the effect is thus reversibly released in the mannitol solution. No hydrolytic activity on GTP, however, is found in the mannitol soluble fraction. 4. The cyclic nucleotide phosphodiesterase is eluted from the rods in the mannitol solution, and is reaggregated to the rods in the presence of salts; once recombined with the rods, it can be activated by light. 5. The activation of the phosphodiesterase by light is present in the absence of added nucleotide triphosphates."}
{"id": "PMID:209181", "title": "Adenosine-induced release of cyclic adenosine 3',5'-monophosphate from the left ventricle in the anaesthetized intact dog.", "content": "1. The influence of adenosine on the release of cyclic adenosine 3',5'-monophosphate (cyclic AMP) from the heart was examined in twenty-two anaesthetized intact dogs. The animals were pre-treated with propranolol and vagotomized. The rate of nucleotide release from the left ventricle was determined as the product of the left ventricular myocardial plasma flow and the coronary veno-arterial difference in plasma nucleotide concentration. 2. Adenosine was infused into the left ventricle during three successive 15 min periods at rates of 25, 50 and 100 n-mole/kg. min, respectively. The mean blood pressure in the ascending aorta was prevented from falling by inflating a balloon placed into the thoracic aorta. The measurements were performed before the infusion and at the 10th min of each infusion period. The values given are means +/- S.E. 3. During the 45 min infusion of adenosine at increasing rate, the cyclic AMP concentration in arterial plasma increased from 7.0 +/- 0.3 to 14.0 +/- 0.9 p-mole/ml. The nucleotide was released from the left ventricle at rates increasing from 48.2 +/- 7.1 to 206.5 +/- 56.2 p-mole/100 g. min while the left ventricular myocardial blood flow increased from 127 +/- 6 to 399 +/- 33 ml./100 g.min. The oxygen consumption of the left ventricle was not modified. 4. When adenosine was infused at a rate of 100 n-mol/kg.min, the thorax was opened and the apex of the heart and the left atrial appendage were removed for nucleotide assay. The cardiac cyclic AMP concentration did not differ from that observed in control dogs. 5. The results suggest that cyclic AMP is likely to be involved in the membrane and cellular events underlying the relaxant effect of adenosine on the coronary smooth muscle. The lack of change in cardiac cyclic AMP concentration, as determined by whole tissue extractions, is consistent with a study by others showing that, under normoxic conditions, cyclic AMP is released from a small, compartmentalized fraction of the cyclic AMP content of the heart. The elevation of the plasma nucleotide concentration could result from adenosine effects on various cell systems or organs, in addition to the observed release from the heart.", "contents": "Adenosine-induced release of cyclic adenosine 3',5'-monophosphate from the left ventricle in the anaesthetized intact dog. 1. The influence of adenosine on the release of cyclic adenosine 3',5'-monophosphate (cyclic AMP) from the heart was examined in twenty-two anaesthetized intact dogs. The animals were pre-treated with propranolol and vagotomized. The rate of nucleotide release from the left ventricle was determined as the product of the left ventricular myocardial plasma flow and the coronary veno-arterial difference in plasma nucleotide concentration. 2. Adenosine was infused into the left ventricle during three successive 15 min periods at rates of 25, 50 and 100 n-mole/kg. min, respectively. The mean blood pressure in the ascending aorta was prevented from falling by inflating a balloon placed into the thoracic aorta. The measurements were performed before the infusion and at the 10th min of each infusion period. The values given are means +/- S.E. 3. During the 45 min infusion of adenosine at increasing rate, the cyclic AMP concentration in arterial plasma increased from 7.0 +/- 0.3 to 14.0 +/- 0.9 p-mole/ml. The nucleotide was released from the left ventricle at rates increasing from 48.2 +/- 7.1 to 206.5 +/- 56.2 p-mole/100 g. min while the left ventricular myocardial blood flow increased from 127 +/- 6 to 399 +/- 33 ml./100 g.min. The oxygen consumption of the left ventricle was not modified. 4. When adenosine was infused at a rate of 100 n-mol/kg.min, the thorax was opened and the apex of the heart and the left atrial appendage were removed for nucleotide assay. The cardiac cyclic AMP concentration did not differ from that observed in control dogs. 5. The results suggest that cyclic AMP is likely to be involved in the membrane and cellular events underlying the relaxant effect of adenosine on the coronary smooth muscle. The lack of change in cardiac cyclic AMP concentration, as determined by whole tissue extractions, is consistent with a study by others showing that, under normoxic conditions, cyclic AMP is released from a small, compartmentalized fraction of the cyclic AMP content of the heart. The elevation of the plasma nucleotide concentration could result from adenosine effects on various cell systems or organs, in addition to the observed release from the heart."}
{"id": "PMID:209184", "title": "Gold-induced thrombocytopenia.", "content": "Ten patients with rheumatoid arhritis treated with gold sodium thiomalate developed thrombocytopenia without bone marrow asplasia. There was no life-threatening blood loss, but petechiae, purpura, or echymoses were seen in eight patients. The serum gold levels monitored in one patient did not exceed levels seen in patients without thrombocytopenia. In three cases peripheral blood lymphocytes were cultured in the presence of gold and tritiated thymidine incorporation was significantly increased. Eight patients responded to steroid therapy, one patient to BAL and pencillamine, and one patient to vincristine.", "contents": "Gold-induced thrombocytopenia. Ten patients with rheumatoid arhritis treated with gold sodium thiomalate developed thrombocytopenia without bone marrow asplasia. There was no life-threatening blood loss, but petechiae, purpura, or echymoses were seen in eight patients. The serum gold levels monitored in one patient did not exceed levels seen in patients without thrombocytopenia. In three cases peripheral blood lymphocytes were cultured in the presence of gold and tritiated thymidine incorporation was significantly increased. Eight patients responded to steroid therapy, one patient to BAL and pencillamine, and one patient to vincristine."}
{"id": "PMID:209186", "title": "Conformation of 2,9-dimethyl-3'-hydroxy-5-phenyl-6,7-genzomorphan and its relation to other analgetics and enkephalin.", "content": "X-ray crystallographic data for 2,9-dimethyl-3'-hydroxy-5-phenyl-6,7-benzomorphan (I) as its p-bromobenzoyl ester are presented. The structure of I is compared with that of morphine, meperidine, alpha-allylprodine, methadone, and moramide as well as with a proposed structure of the enkephalins. A quantitative relationship is found between in vitro opiate receptor binding potency and in vivo analgesia for analgesics of diverse structure, including I. A new view of the analgetic pharmacophore is presented. Programs for the TI Programmable 59 calculator are described for conversion of X-ray crystallographic data to rectangular coordinates with reorientation of the molecule and for the calculation of torsion angles.", "contents": "Conformation of 2,9-dimethyl-3'-hydroxy-5-phenyl-6,7-genzomorphan and its relation to other analgetics and enkephalin. X-ray crystallographic data for 2,9-dimethyl-3'-hydroxy-5-phenyl-6,7-benzomorphan (I) as its p-bromobenzoyl ester are presented. The structure of I is compared with that of morphine, meperidine, alpha-allylprodine, methadone, and moramide as well as with a proposed structure of the enkephalins. A quantitative relationship is found between in vitro opiate receptor binding potency and in vivo analgesia for analgesics of diverse structure, including I. A new view of the analgetic pharmacophore is presented. Programs for the TI Programmable 59 calculator are described for conversion of X-ray crystallographic data to rectangular coordinates with reorientation of the molecule and for the calculation of torsion angles."}
{"id": "PMID:209187", "title": "Aromatic esters of nonquaternary carbon-4 piperidinols as analgesics.", "content": "Aromatic carboxylic esters of 1-methyl-4-piperidinol were prepared and evaluated for analgesic activity. In addition, aralkyl, alkyl, and cycloalkyl carboxylates of the 4-piperidinol system and 3,4-dimethoxybenzoates of isomeric piperidinols (24-26) were synthesized. The 3,4-dimethoxybenzoate 23 was nearly twice as active as codeine in the mouse hot-plate assay. In monkeys, 23 showed no morphine-like physical dependence liability, cis- and trans-1,3-dimethyl-4-piperidinol esters 24 and 25 showed no binding to the opiate receptor in rat brain homogenates. The 3- and 4-monosubstituted and the 3,4-disubstituted benzoate esters were examined for qualitative structure-activity relationships with respect to parameters Esc and pi. Various structural features of this series of compounds that may have an affinity for receptor binding sites are discussed.", "contents": "Aromatic esters of nonquaternary carbon-4 piperidinols as analgesics. Aromatic carboxylic esters of 1-methyl-4-piperidinol were prepared and evaluated for analgesic activity. In addition, aralkyl, alkyl, and cycloalkyl carboxylates of the 4-piperidinol system and 3,4-dimethoxybenzoates of isomeric piperidinols (24-26) were synthesized. The 3,4-dimethoxybenzoate 23 was nearly twice as active as codeine in the mouse hot-plate assay. In monkeys, 23 showed no morphine-like physical dependence liability, cis- and trans-1,3-dimethyl-4-piperidinol esters 24 and 25 showed no binding to the opiate receptor in rat brain homogenates. The 3- and 4-monosubstituted and the 3,4-disubstituted benzoate esters were examined for qualitative structure-activity relationships with respect to parameters Esc and pi. Various structural features of this series of compounds that may have an affinity for receptor binding sites are discussed."}
{"id": "PMID:209188", "title": "Antiviral activity of some beta-diketones. 3. Aryl bis(beta-diketones). Antiherpetic activity.", "content": "A series of bis(beta-diketones) was synthesized and tested in vitro for antiviral actitity against herpes simplex type 2. Two parameters which were studied in an effort to optimize activity were the nature of the aryl group and the length of the alkyl bridge. One of the more active compounds, 4,4'-[(1,4-phenylenedioxy)bis(6,1-hexanediyl)]-bis[3,5-heptanedione] (6), was evaluated more extensively and found to inhibit the cytopathic effect in tissue culture of herpes simplex virus type 1 as well as type 2. Compound 6 was evaluated in vivo topically against herpes simplex type 1 in experimentally induced skin infections in guinea pigs. A topical treatment with 2% of 6 in a vanishing cream base, administered 24 h postinfection applied five times daily for 4 days, significantly reduced the number and size of herpetic vesicles.", "contents": "Antiviral activity of some beta-diketones. 3. Aryl bis(beta-diketones). Antiherpetic activity. A series of bis(beta-diketones) was synthesized and tested in vitro for antiviral actitity against herpes simplex type 2. Two parameters which were studied in an effort to optimize activity were the nature of the aryl group and the length of the alkyl bridge. One of the more active compounds, 4,4'-[(1,4-phenylenedioxy)bis(6,1-hexanediyl)]-bis[3,5-heptanedione] (6), was evaluated more extensively and found to inhibit the cytopathic effect in tissue culture of herpes simplex virus type 1 as well as type 2. Compound 6 was evaluated in vivo topically against herpes simplex type 1 in experimentally induced skin infections in guinea pigs. A topical treatment with 2% of 6 in a vanishing cream base, administered 24 h postinfection applied five times daily for 4 days, significantly reduced the number and size of herpetic vesicles."}
{"id": "PMID:209189", "title": "Mercaptoimidazolylpropionic acid hydrobromide. Inhibition of tadpole collagenase and related properties.", "content": "A mercapto analogue of histidine (1), (RS)-2-mercapto-3-(5-imidazolyl)propionic acid (2), was prepared by treatment of (RS)-2-bromo-3-(5-imidazolyl)propionic acid with trithiocarbonate. Decomposition of the resulting intermediate with hydrochloric acid followed by Sephadex G-15 chromatography permitted isolation of 2 as a hydrobromide complex having unusual stability and properties as evidenced by IR and 1H NMR data. The potency of this complex in inhibiting tissue (Rana catesbiana) collagenase was estimated by radial diffusion assay. The amount of 2 required to produce 50% inhibition was 3.8 +/- 1.5 mM compared to 8.7 +/- 2.5 mM for cysteine. Preliminary tests of oxygen susceptibility, mutagenicity, and toxicity suggest that this substance may warrant study as a therapeutic agent for control of collagenase-linked corneal ulcerations.", "contents": "Mercaptoimidazolylpropionic acid hydrobromide. Inhibition of tadpole collagenase and related properties. A mercapto analogue of histidine (1), (RS)-2-mercapto-3-(5-imidazolyl)propionic acid (2), was prepared by treatment of (RS)-2-bromo-3-(5-imidazolyl)propionic acid with trithiocarbonate. Decomposition of the resulting intermediate with hydrochloric acid followed by Sephadex G-15 chromatography permitted isolation of 2 as a hydrobromide complex having unusual stability and properties as evidenced by IR and 1H NMR data. The potency of this complex in inhibiting tissue (Rana catesbiana) collagenase was estimated by radial diffusion assay. The amount of 2 required to produce 50% inhibition was 3.8 +/- 1.5 mM compared to 8.7 +/- 2.5 mM for cysteine. Preliminary tests of oxygen susceptibility, mutagenicity, and toxicity suggest that this substance may warrant study as a therapeutic agent for control of collagenase-linked corneal ulcerations."}
{"id": "PMID:209190", "title": "Nucleoside 5'-monophosphate analogues. Synthesis of 5'-sulfamino-5'-deoxynucleosides.", "content": "The synthesis of two new nucleotide analogues is described. 5'-Sulfamino-5'-deoxyadenosine (1) was prepared by reaction of 5'-amino-5'-deoxyadenosine with (CH3)3N.203, and 5'-sulfamino-5'-deoxythymidine (2) was prepared from 5'-amino-5'-deoxythymidine by a similar reaction. The 5'-sulfamino nucleosides are shown to be quite stable to hydrolysis in acidic or basic aqueous solution Tests show that these compounds do not inhibit the growth of Escherichia coli or L1210 cells at concentrations less than 10(-4) M. At 10(-4) M compound 2 was found to give 70% inhibition of the replication of herpes simplex virus (type 1) with no effect on host cell growth (CV-1 monkey line).", "contents": "Nucleoside 5'-monophosphate analogues. Synthesis of 5'-sulfamino-5'-deoxynucleosides. The synthesis of two new nucleotide analogues is described. 5'-Sulfamino-5'-deoxyadenosine (1) was prepared by reaction of 5'-amino-5'-deoxyadenosine with (CH3)3N.203, and 5'-sulfamino-5'-deoxythymidine (2) was prepared from 5'-amino-5'-deoxythymidine by a similar reaction. The 5'-sulfamino nucleosides are shown to be quite stable to hydrolysis in acidic or basic aqueous solution Tests show that these compounds do not inhibit the growth of Escherichia coli or L1210 cells at concentrations less than 10(-4) M. At 10(-4) M compound 2 was found to give 70% inhibition of the replication of herpes simplex virus (type 1) with no effect on host cell growth (CV-1 monkey line)."}
{"id": "PMID:209191", "title": "Synthesis of branched-chain apiosylpyrimidines and their inhibition of lymphocyte proliferation.", "content": "Branched-chain nucleosides containing beta-D-apio-L-furanose were synthesized by condensation of the bis(trimethylsiyl) derivative of uracil (11), thymine (12), 5-fromouracil (13), and 5-iodouracil (14) with the protected 1-O-acetylapiose in the presence of a Friedel-Crafts catalyst. D-Apio-L-furanosyluracil (11) and D-apio-L-furanosylthymine (12) show immunosuppressive activity for rat T-lymphocytes stimulated to grow by phytohemagglutinin but exhibit no inhibitory activity against herpes simplex virus. Compounds 11--14 did not inhibit herpes simplex virus replication, while low inhibition was obtained with the one nucleoside containing D-apio-D-furanose, D-apio-D-furanosyladenine. D-Apio-L-furanosyl-5-bromouracil (13), D-apio-L-furanosyl-5-iodouracil (14), bromouridine, and iodouridine suppressed growth of human lymphoblasts significantly more than the nonhalogenated apiosylphrimidines.", "contents": "Synthesis of branched-chain apiosylpyrimidines and their inhibition of lymphocyte proliferation. Branched-chain nucleosides containing beta-D-apio-L-furanose were synthesized by condensation of the bis(trimethylsiyl) derivative of uracil (11), thymine (12), 5-fromouracil (13), and 5-iodouracil (14) with the protected 1-O-acetylapiose in the presence of a Friedel-Crafts catalyst. D-Apio-L-furanosyluracil (11) and D-apio-L-furanosylthymine (12) show immunosuppressive activity for rat T-lymphocytes stimulated to grow by phytohemagglutinin but exhibit no inhibitory activity against herpes simplex virus. Compounds 11--14 did not inhibit herpes simplex virus replication, while low inhibition was obtained with the one nucleoside containing D-apio-D-furanose, D-apio-D-furanosyladenine. D-Apio-L-furanosyl-5-bromouracil (13), D-apio-L-furanosyl-5-iodouracil (14), bromouridine, and iodouridine suppressed growth of human lymphoblasts significantly more than the nonhalogenated apiosylphrimidines."}
{"id": "PMID:209197", "title": "Protection against 7, 12-dimethylbenz[a]anthracene-induced rat mammary carcinoma by infection with mouse xenotropic type C virus.", "content": "A single ip inoculation of female, outbred Sprague-Dawley rats with a viable mouse xenotropic type C virus significantly reduced the incidence and/or retarded the development of mammary carcinoma induced by 7, 12-dimethylbenz[a]anthracene administered orally 7 days after virus. Although infectious virus could not be isolated from organs of infected rats, high titers of circulating and tumor-associated antibodies were detected against the viral internal core protein p30, and a low-grade antibody response to intact virus or envelope glycoprotein was found. Moreover, a cell-mediated immune response, measured by lymphocyte transformation, was detected with the use of intact virus but not with p30 antigen. No immunity developed after a single inoculation of UV-inactivated virus. These data indicated that inoculation of adult individuals of heterologous species with viable xenotropic mouse type C virus resulted in the rapid disappearance of infectious virus from the recipient, followed by the development of both humoral and cellular immunity to virion constituents. These events led, by unknown mechanisms, to the effective retardation of chemical carcinogenesis when infection preceded carcinogen administration.", "contents": "Protection against 7, 12-dimethylbenz[a]anthracene-induced rat mammary carcinoma by infection with mouse xenotropic type C virus. A single ip inoculation of female, outbred Sprague-Dawley rats with a viable mouse xenotropic type C virus significantly reduced the incidence and/or retarded the development of mammary carcinoma induced by 7, 12-dimethylbenz[a]anthracene administered orally 7 days after virus. Although infectious virus could not be isolated from organs of infected rats, high titers of circulating and tumor-associated antibodies were detected against the viral internal core protein p30, and a low-grade antibody response to intact virus or envelope glycoprotein was found. Moreover, a cell-mediated immune response, measured by lymphocyte transformation, was detected with the use of intact virus but not with p30 antigen. No immunity developed after a single inoculation of UV-inactivated virus. These data indicated that inoculation of adult individuals of heterologous species with viable xenotropic mouse type C virus resulted in the rapid disappearance of infectious virus from the recipient, followed by the development of both humoral and cellular immunity to virion constituents. These events led, by unknown mechanisms, to the effective retardation of chemical carcinogenesis when infection preceded carcinogen administration."}
{"id": "PMID:209199", "title": "Effect of reovirus infection on pulmonary tumor response to urethan in strain A mice.", "content": "The effect of reovirus type 3 infection on the pulmonary adenoma response to urethan in strain A mice was examined. Urethan carcinogenesis in this system was suppressed from 30 to 60% when mice were exposed to reovirus either 6 days before, on the same day as, or 14 days after urethan administration. These findings suggested that reovirus infection interfered with the progression of urethan-induced pulmonary adenoma rather than the induction of lung tumors by urethan. When mice received multiple exposures to reovirus, the lung tumor response was enhanced. These findings indicated that reovirus infection in particular and virus infection in general may play an important role in the carcinogenic response to environmental chemicals.", "contents": "Effect of reovirus infection on pulmonary tumor response to urethan in strain A mice. The effect of reovirus type 3 infection on the pulmonary adenoma response to urethan in strain A mice was examined. Urethan carcinogenesis in this system was suppressed from 30 to 60% when mice were exposed to reovirus either 6 days before, on the same day as, or 14 days after urethan administration. These findings suggested that reovirus infection interfered with the progression of urethan-induced pulmonary adenoma rather than the induction of lung tumors by urethan. When mice received multiple exposures to reovirus, the lung tumor response was enhanced. These findings indicated that reovirus infection in particular and virus infection in general may play an important role in the carcinogenic response to environmental chemicals."}
{"id": "PMID:209200", "title": "Virus-specific markers and virus-like particles in cell lines of tumors produced by CELO virus in Syrian golden hamsters.", "content": "Cell lines were established from 2 primary hepatocellular carcinomas (HC's) and 3 sarcomas produced in Syrian golden hamsters inoculated as newborns with chicken embryo lethal orphan (CELO) virus. Cell lines from 2 sarcomas (COT, CMT) and 1 HC (CEHEP) produced CELO virus-specific T-antigen. The antigen was not detected in cells of the third sarcoma line (RCT) until they had undergone more than 34 passages in vitro. Although 5-10% of cells in the second HC line (CILT/2) contained T-antigen during early passages, it was not demonstrable after the fifth subculture. Nevertheless, cells of both HC lines possessed CELO virus tumor-specific transplantation antigen. All 5 cell lines also contained hamster type R particles, and both HC lines had type C and intracytoplasmic type A particles. The percentage of carcinoma cells producing type R particles increased during cultivation in vitro, whereas the number of cells with type A particles decreased. Treatment with dibutyryl cyclic AMP and theophylline enhanced the number of cells producing type C particles in 1 HC line and type R particles in 2 sarcoma lines.", "contents": "Virus-specific markers and virus-like particles in cell lines of tumors produced by CELO virus in Syrian golden hamsters. Cell lines were established from 2 primary hepatocellular carcinomas (HC's) and 3 sarcomas produced in Syrian golden hamsters inoculated as newborns with chicken embryo lethal orphan (CELO) virus. Cell lines from 2 sarcomas (COT, CMT) and 1 HC (CEHEP) produced CELO virus-specific T-antigen. The antigen was not detected in cells of the third sarcoma line (RCT) until they had undergone more than 34 passages in vitro. Although 5-10% of cells in the second HC line (CILT/2) contained T-antigen during early passages, it was not demonstrable after the fifth subculture. Nevertheless, cells of both HC lines possessed CELO virus tumor-specific transplantation antigen. All 5 cell lines also contained hamster type R particles, and both HC lines had type C and intracytoplasmic type A particles. The percentage of carcinoma cells producing type R particles increased during cultivation in vitro, whereas the number of cells with type A particles decreased. Treatment with dibutyryl cyclic AMP and theophylline enhanced the number of cells producing type C particles in 1 HC line and type R particles in 2 sarcoma lines."}
{"id": "PMID:209201", "title": "Delay of tumor growth in hamsters treated with lynestrenol and effect of Staphylococcus aureus Cowan A.", "content": "The action of lynestrenol, a synthetic progesterone-like substance, was studied in Syrian golden hamsters inoculated with cells transformed by herpes simplex virus type I. Daily ip injections of 1 mg lynesterol/kg delayed tumor growth. Lynestrenol alone only slightly increased the survival of the animals. This effect was more marked when the animals were also given injections of Staphylococcus aureus Cowan A. Survivors showed an increased resistance to challenge with infected cells. Hamsters previously given injections of killed transformed cells and then challenged with living cells showed a facilitation of tumor growth. This facilitation was inhibited by lynestrenol alone or combined with S. aureus Cowan A.", "contents": "Delay of tumor growth in hamsters treated with lynestrenol and effect of Staphylococcus aureus Cowan A. The action of lynestrenol, a synthetic progesterone-like substance, was studied in Syrian golden hamsters inoculated with cells transformed by herpes simplex virus type I. Daily ip injections of 1 mg lynesterol/kg delayed tumor growth. Lynestrenol alone only slightly increased the survival of the animals. This effect was more marked when the animals were also given injections of Staphylococcus aureus Cowan A. Survivors showed an increased resistance to challenge with infected cells. Hamsters previously given injections of killed transformed cells and then challenged with living cells showed a facilitation of tumor growth. This facilitation was inhibited by lynestrenol alone or combined with S. aureus Cowan A."}
{"id": "PMID:209202", "title": "Epstein-Barr virus infections in Brazil. II. Hodgkin's disease.", "content": "Sixty-seven cases of Hodgkin's disease (HD) occurring in S\u00e3o Paulo, Brazil, were studied. Males with HD predominated over females 2.3 to 1. Sixty-six percent of the cases occurred in patients under 30 years of age, 31.7% under 20 years of age, and only 7.5% after 50 years of age. Lymphocyte predominance and mixed cellularity histologic types were most common in patients less than 15 years old, and nodular sclerosis was most common in the 15- to 19-year-old group. Sera from all patients had antibody to the viral capsid antigen (VCA) of Epstein-Barr virus (EBV). The geometric mean titer (GMT) of VCA antibody with the use of Jijoye cells as antigen was 1:162, and 31.3% of patients had titers of 1:320 or more; in controls, the GMT was 1:67 and 3.8% had titers of 1:320 or more. Similar results were obtained when EB-3 cells were used as antigen. The highest titers occurred in males, in mixed cellularity and lymphocyte depletion forms, and in stage 2 of illness. EBV-specific IgM antibody and heterophile antibody levels were not elevated, but 20.5% of the HD patients had antibody to the early antigen of EBV present in their sera. Antibody levels for herpes simplex virus, cytomegalovirus, rubella, measles, parainfluenza viruses, and papovavirus were not significantly elevated over those in matched controls.", "contents": "Epstein-Barr virus infections in Brazil. II. Hodgkin's disease. Sixty-seven cases of Hodgkin's disease (HD) occurring in S\u00e3o Paulo, Brazil, were studied. Males with HD predominated over females 2.3 to 1. Sixty-six percent of the cases occurred in patients under 30 years of age, 31.7% under 20 years of age, and only 7.5% after 50 years of age. Lymphocyte predominance and mixed cellularity histologic types were most common in patients less than 15 years old, and nodular sclerosis was most common in the 15- to 19-year-old group. Sera from all patients had antibody to the viral capsid antigen (VCA) of Epstein-Barr virus (EBV). The geometric mean titer (GMT) of VCA antibody with the use of Jijoye cells as antigen was 1:162, and 31.3% of patients had titers of 1:320 or more; in controls, the GMT was 1:67 and 3.8% had titers of 1:320 or more. Similar results were obtained when EB-3 cells were used as antigen. The highest titers occurred in males, in mixed cellularity and lymphocyte depletion forms, and in stage 2 of illness. EBV-specific IgM antibody and heterophile antibody levels were not elevated, but 20.5% of the HD patients had antibody to the early antigen of EBV present in their sera. Antibody levels for herpes simplex virus, cytomegalovirus, rubella, measles, parainfluenza viruses, and papovavirus were not significantly elevated over those in matched controls."}
{"id": "PMID:209203", "title": "Chromosome changes (trisomies #15 and 17) associated with tumor progression in leukemias induced by radiation leukemia virus.", "content": "An experimental system was developed that permitted nonrandom chromosome changes that occur in radiation leukemia virus (RadLV)-induced lymphomas to be followed during tumor progression. RadLV variant-induced preleukemia and leukemia cells originating from female inbred C57BL/6 mice were injected into male animals of the same strain. Since all donors were females and all recipients were males, the sex chromosome complements (XX and XY) were used to distinguish the preleukemia and leukemia cells from those of host origin. The G-banding analysis revealed that more than 50% of animals that were inoculated with preleukemia cells and that developed leukemia possessed tumor stem-lines of 41 chromosomes with a tristomy of chromosome #15. In animals inoculated with overt leukemia cells and in which tumor progression occurred, the G-banding an additional trisomy of chromosome #17. The cytogenic data strongly suggested that the trisomy of chromosome #15 was the first specific tumor-associated chromosome change that occurred in the process of conversion of RadLV-induced preleukemia cells to fully autonomous tumor cells.", "contents": "Chromosome changes (trisomies #15 and 17) associated with tumor progression in leukemias induced by radiation leukemia virus. An experimental system was developed that permitted nonrandom chromosome changes that occur in radiation leukemia virus (RadLV)-induced lymphomas to be followed during tumor progression. RadLV variant-induced preleukemia and leukemia cells originating from female inbred C57BL/6 mice were injected into male animals of the same strain. Since all donors were females and all recipients were males, the sex chromosome complements (XX and XY) were used to distinguish the preleukemia and leukemia cells from those of host origin. The G-banding analysis revealed that more than 50% of animals that were inoculated with preleukemia cells and that developed leukemia possessed tumor stem-lines of 41 chromosomes with a tristomy of chromosome #15. In animals inoculated with overt leukemia cells and in which tumor progression occurred, the G-banding an additional trisomy of chromosome #17. The cytogenic data strongly suggested that the trisomy of chromosome #15 was the first specific tumor-associated chromosome change that occurred in the process of conversion of RadLV-induced preleukemia cells to fully autonomous tumor cells."}
{"id": "PMID:209204", "title": "Quantitation of secretory component levels in cyst fluids, ascitic fluids, and sera from ovarian adenocarcinoma patients.", "content": "A secretory component (SC) was detected by radioimmunoassay in the cyst fluids, ascitic fluids, and sera from patients with ovarian adenocarcinomas. Serous cyst fluids and ascitic fluids showed lower levels (expressed as means +/- SE) of SC (1.37 +/- 0.37 and 1.24 +/- 0.24 microgram/ml, respectively) than mucinous cyst fluids (181.50 +/- 50.40 microgram/ml). SC levels in the sera of all patients with ovarian adenocarcinoma were high (12.67 +/- 1.43 microgram/ml) when compared to SC levels in the sera of normal individuals (2.34 +/- 0.41 microgram/ml). Sera from patients with ovarian cancers diagnosed as serous, mucinous, papillary, and poorly differentiated adenocarcinomas showed SC levels of 9.93 +/- 1.68, 22.44 +/- 3.24, 7.35 +/- 1.13, and 10.10 +/- 1.58 microgram/ml, respectively.", "contents": "Quantitation of secretory component levels in cyst fluids, ascitic fluids, and sera from ovarian adenocarcinoma patients. A secretory component (SC) was detected by radioimmunoassay in the cyst fluids, ascitic fluids, and sera from patients with ovarian adenocarcinomas. Serous cyst fluids and ascitic fluids showed lower levels (expressed as means +/- SE) of SC (1.37 +/- 0.37 and 1.24 +/- 0.24 microgram/ml, respectively) than mucinous cyst fluids (181.50 +/- 50.40 microgram/ml). SC levels in the sera of all patients with ovarian adenocarcinoma were high (12.67 +/- 1.43 microgram/ml) when compared to SC levels in the sera of normal individuals (2.34 +/- 0.41 microgram/ml). Sera from patients with ovarian cancers diagnosed as serous, mucinous, papillary, and poorly differentiated adenocarcinomas showed SC levels of 9.93 +/- 1.68, 22.44 +/- 3.24, 7.35 +/- 1.13, and 10.10 +/- 1.58 microgram/ml, respectively."}
{"id": "PMID:209205", "title": "Type B and type C RNA tumor virus replication in single cells. Electron microscopy with tannic acid.", "content": "Simultaneous replication of murine mammary tumor virus (type B) and murine leukemia virus (type C) was demonstrated electron microscopically along continuous stretches of the plasma membrane of single cells in cultures ofthe Mm5mt/c1 cell line. Types B and C virus buds were discriminated in thin sections with the aid of a tannic acid fixative that revealed the type B surface spikes as a homogeneous band of intermediate density and constant width on the surfaces of some buds (type B), whereas others (type C) remained with relatively smooth envelopes. Both types B and C buds may contain morphologically identical horseshoe-shaped nucleoids. Therefore, their identify (type B or C) could be ascertained in thin sections only on the basis of recognition of surface spikes.", "contents": "Type B and type C RNA tumor virus replication in single cells. Electron microscopy with tannic acid. Simultaneous replication of murine mammary tumor virus (type B) and murine leukemia virus (type C) was demonstrated electron microscopically along continuous stretches of the plasma membrane of single cells in cultures ofthe Mm5mt/c1 cell line. Types B and C virus buds were discriminated in thin sections with the aid of a tannic acid fixative that revealed the type B surface spikes as a homogeneous band of intermediate density and constant width on the surfaces of some buds (type B), whereas others (type C) remained with relatively smooth envelopes. Both types B and C buds may contain morphologically identical horseshoe-shaped nucleoids. Therefore, their identify (type B or C) could be ascertained in thin sections only on the basis of recognition of surface spikes."}
{"id": "PMID:209206", "title": "Pharmacology of the brachium conjunctivum: red nucleus synaptic system in the baboon.", "content": "Acetylcholine, biogenic amines, and certain amino acids were applied by microiontophoresis to parvicellular and magnocellular red nucleus (RN) neurons of baboon while recording brachium conjunctivum (BC)-evoked and amino acid-evoked unit discharge from these neurons. Glycine, gamma-aminobutyric acid, and beta-alanine were potent depressants of BC-RN synaptic transmission, amino acid-evoked firing, and spontaneous activity of all RN neurons studied. Glycine was clearly more potent than the other 2 depressant amino acids. L-Glutamic and DL-homocysteic acid were strong excitants of all RN neurons tested. Dopamine, noradrenaline, and 5-hydroxytryptamine depressed the excitability of both parvicellular and magnocellular RN neurons; no excitatory effects were observed with these biogenic amines on RN neurons. Acetylcholine increased the rate of firing of spontaneously discharging parvicellular RN neurons and facilitated the amino acid-induced firing of these same neurons. Acetylcholine did not facilitate BC-RN synaptic transmission nor could this transmission be blocked by cholinergic antagonists. Unlike parvicellular RN neurons, the responsiveness of magnocellular neurons was either unaltered by acetylcholine or slightly decreased. These experiments demonstrate a difference in the pharmacologic responsiveness of parvicellular and magnocellular RN neurons to acetylcholine but do not provide evidence for a cholinergic input to RN via the brachium conjunctivum.", "contents": "Pharmacology of the brachium conjunctivum: red nucleus synaptic system in the baboon. Acetylcholine, biogenic amines, and certain amino acids were applied by microiontophoresis to parvicellular and magnocellular red nucleus (RN) neurons of baboon while recording brachium conjunctivum (BC)-evoked and amino acid-evoked unit discharge from these neurons. Glycine, gamma-aminobutyric acid, and beta-alanine were potent depressants of BC-RN synaptic transmission, amino acid-evoked firing, and spontaneous activity of all RN neurons studied. Glycine was clearly more potent than the other 2 depressant amino acids. L-Glutamic and DL-homocysteic acid were strong excitants of all RN neurons tested. Dopamine, noradrenaline, and 5-hydroxytryptamine depressed the excitability of both parvicellular and magnocellular RN neurons; no excitatory effects were observed with these biogenic amines on RN neurons. Acetylcholine increased the rate of firing of spontaneously discharging parvicellular RN neurons and facilitated the amino acid-induced firing of these same neurons. Acetylcholine did not facilitate BC-RN synaptic transmission nor could this transmission be blocked by cholinergic antagonists. Unlike parvicellular RN neurons, the responsiveness of magnocellular neurons was either unaltered by acetylcholine or slightly decreased. These experiments demonstrate a difference in the pharmacologic responsiveness of parvicellular and magnocellular RN neurons to acetylcholine but do not provide evidence for a cholinergic input to RN via the brachium conjunctivum."}
{"id": "PMID:209209", "title": "Aanlysis of dCMP deaminase and CDP reductase levels in hamster cells infected by herpes simplex virus.", "content": "Several enzymatic activities involved in the biosynthetic pathways of nucleotides, including thymidine kinase, which has been used as a biochemical marker in studies of gene transfer, are induced by herpes simplex virus (HSV). The utility of additional markers prompted us to reanalyze the effects of HSV infection on the activities of two other enzymes for which direct selective methods can be devised: dCMP deaminase and CDP reductase. For this purpose, mutant Chinese hamster (lA1) cells devoid of dCMP deaminase activity or Syrian hamster (BHK-21/C13) cells were infected by HSV type 1 or 2, and the activities of thymidine kinase, dCMP deaminase, and CDP reductase were measured in the cell extracts. The reported induction of thymidine kinase and CDP reductase by HSV was confirmed, whereas the stimulation of dCMP deaminase activity could not be observed. For both cell lines, the HSV-induced CDP reductase differed from the host enzyme by sensitivity to inhibition by both dTTP and dATP. This property should be helpful in developing a selection system for this activity.", "contents": "Aanlysis of dCMP deaminase and CDP reductase levels in hamster cells infected by herpes simplex virus. Several enzymatic activities involved in the biosynthetic pathways of nucleotides, including thymidine kinase, which has been used as a biochemical marker in studies of gene transfer, are induced by herpes simplex virus (HSV). The utility of additional markers prompted us to reanalyze the effects of HSV infection on the activities of two other enzymes for which direct selective methods can be devised: dCMP deaminase and CDP reductase. For this purpose, mutant Chinese hamster (lA1) cells devoid of dCMP deaminase activity or Syrian hamster (BHK-21/C13) cells were infected by HSV type 1 or 2, and the activities of thymidine kinase, dCMP deaminase, and CDP reductase were measured in the cell extracts. The reported induction of thymidine kinase and CDP reductase by HSV was confirmed, whereas the stimulation of dCMP deaminase activity could not be observed. For both cell lines, the HSV-induced CDP reductase differed from the host enzyme by sensitivity to inhibition by both dTTP and dATP. This property should be helpful in developing a selection system for this activity."}
{"id": "PMID:209210", "title": "5'-terminal nucleotide sequences of mammalian type C helper viruses are conserved in the genomes of replication-defective mammalian transforming viruses.", "content": "The RNAs of replication-defective murine and primate type C transforming viruses were analyzed for the presence of nucleotide sequences homologous to the genomes of their respective helper type C viruses by using DNAs complementary (cDNA) to either the 5'-terminal (cDNA5') or total (cDNAtotal) nucleotide sequences of the helper virus RNA. The defective viruses examined have previously been shown to vary in their ability to express helper viral gag gene proteins. With cDNAtotal as a probe, these transforming viruses were shown to vary in their representation of helper sequences (15 to 60% hybridization of cDNAtotal). In striking contrast, 5'-terminal-specific sequences of the helper virus were conserved in the RNAs of every transforming virus tested (is greater than 80% hybridization of cDNA5'). These findings suggest a critical role for these sequences in the life cycle of the defective transforming virus.", "contents": "5'-terminal nucleotide sequences of mammalian type C helper viruses are conserved in the genomes of replication-defective mammalian transforming viruses. The RNAs of replication-defective murine and primate type C transforming viruses were analyzed for the presence of nucleotide sequences homologous to the genomes of their respective helper type C viruses by using DNAs complementary (cDNA) to either the 5'-terminal (cDNA5') or total (cDNAtotal) nucleotide sequences of the helper virus RNA. The defective viruses examined have previously been shown to vary in their ability to express helper viral gag gene proteins. With cDNAtotal as a probe, these transforming viruses were shown to vary in their representation of helper sequences (15 to 60% hybridization of cDNAtotal). In striking contrast, 5'-terminal-specific sequences of the helper virus were conserved in the RNAs of every transforming virus tested (is greater than 80% hybridization of cDNA5'). These findings suggest a critical role for these sequences in the life cycle of the defective transforming virus."}
{"id": "PMID:209211", "title": "Detection of proviral DNA in horse cells infected with equine infectious anemia virus.", "content": "Equine infectious anemia virus (EIAV) recently has been shown to possess a high-molecular-weight RNA genome and a virion reverse transcriptase. We completed the demonstration that EIAV is a retrovirus by showing the presence of proviral DNA in equine cells infected in vitro, but not in normal horse DNA. These studies were performed by using a highly representative cDNA probe synthesized by the virion polymerase. It was found that this cDNA reassociated extensively, and with high thermal stability, with either viral RNA or DNA extracted from infected cells, but showed no detectable reassociation with DNA from uninfected horse cells. Similarly, sequences related to EIAV were neither found in the DNA of four other Equus species, nor in a variety of other mammals including sheep, cows, pigs- dogs, cats, and humans; nor did EIAV cDNA hybridize with a variety of other retrovirus RNAs. These experiments were performed under conditions of very low stringency to enable detection of distantly related sequences, with a sufficient ratio of DAN to cDNA to allow detection of less than one viral copy per haploid genome. We conclude that EIAV is not an endogenous virus of the horse or of the other species tested.", "contents": "Detection of proviral DNA in horse cells infected with equine infectious anemia virus. Equine infectious anemia virus (EIAV) recently has been shown to possess a high-molecular-weight RNA genome and a virion reverse transcriptase. We completed the demonstration that EIAV is a retrovirus by showing the presence of proviral DNA in equine cells infected in vitro, but not in normal horse DNA. These studies were performed by using a highly representative cDNA probe synthesized by the virion polymerase. It was found that this cDNA reassociated extensively, and with high thermal stability, with either viral RNA or DNA extracted from infected cells, but showed no detectable reassociation with DNA from uninfected horse cells. Similarly, sequences related to EIAV were neither found in the DNA of four other Equus species, nor in a variety of other mammals including sheep, cows, pigs- dogs, cats, and humans; nor did EIAV cDNA hybridize with a variety of other retrovirus RNAs. These experiments were performed under conditions of very low stringency to enable detection of distantly related sequences, with a sufficient ratio of DAN to cDNA to allow detection of less than one viral copy per haploid genome. We conclude that EIAV is not an endogenous virus of the horse or of the other species tested."}
{"id": "PMID:209212", "title": "Role of the simian virus 40 gene A product in regulation of DNA synthesis in transformed cells.", "content": "Cells transformed by tsA mutants of simian virus 40 (SV40) are temperature sensitive for the maintenance of the transformed phenotype. The kinetics of induction of DNA synthesis were determined for hamster cell transformants shifted to the permissive temperature after a 48-h serum arrest at the nonpermissive temperature. DNAsynthesis was initiated in the tsA transformants by 8 h after shiftdown was maximal by 12 h. The presence or absence of fetal bovine serum at the time of temperature shift had no effect on the kinetics of initiation of DNA synthesis. Analysis of TTP in tsA transformants revealed similar levels of incorporation of [3H]thymidine into TTP at both permissive and nonpermissive temperatures. Autoradiography revealed that by 12 h after a shift to the permissive temperature, approximately 50% of the cells exhibited labeled nuclei after a 60-min pulse with [3H]thymidine, indicating that a majority of the cells were actively synthesizing DNA. By 8 to 12 h after a shiftup of confluent tsA transformants to the nonpermissive temperature, the number of labeled nuclei was reduced to approximately 16%, regardless of serum concentration. These data indicate that the SV40 gene A product, either directly or indirectly, regulates cellular DNA synthesis in transformed cells.", "contents": "Role of the simian virus 40 gene A product in regulation of DNA synthesis in transformed cells. Cells transformed by tsA mutants of simian virus 40 (SV40) are temperature sensitive for the maintenance of the transformed phenotype. The kinetics of induction of DNA synthesis were determined for hamster cell transformants shifted to the permissive temperature after a 48-h serum arrest at the nonpermissive temperature. DNAsynthesis was initiated in the tsA transformants by 8 h after shiftdown was maximal by 12 h. The presence or absence of fetal bovine serum at the time of temperature shift had no effect on the kinetics of initiation of DNA synthesis. Analysis of TTP in tsA transformants revealed similar levels of incorporation of [3H]thymidine into TTP at both permissive and nonpermissive temperatures. Autoradiography revealed that by 12 h after a shift to the permissive temperature, approximately 50% of the cells exhibited labeled nuclei after a 60-min pulse with [3H]thymidine, indicating that a majority of the cells were actively synthesizing DNA. By 8 to 12 h after a shiftup of confluent tsA transformants to the nonpermissive temperature, the number of labeled nuclei was reduced to approximately 16%, regardless of serum concentration. These data indicate that the SV40 gene A product, either directly or indirectly, regulates cellular DNA synthesis in transformed cells."}
{"id": "PMID:209213", "title": "Genome organization of RNA tumor viruses. I. In vitro synthesis of full-genome-length single-stranded and double-stranded viral DNA transcripts.", "content": "Genome-length complementary DNA (cDNA) transcripts were synthesized in vitro by using purified virions of avian myeloblastosis virus. Moloney murine leukemia virus, and clone 124 mouse sarcoma virus. The size of the genomelenth cDNA transcripts was measured on either alkaline sucrose gradients or alkaline agarose gels. The longest cDNA transcripts synthesized by using avian myeloblastosis virus, Moloney murine leukemia virus, and clone 124 mouse sarcoma virus were 7, 9 and 6 kilobases (kb), respectively. The in vitro system used was capable of synthesizing double-stranded DNA, but the plus strands (same polarity as the viral RNA) were only 0.5 to 1.5 kb long. Lone Moloney murine leukemia virus cDNA transcripts were used as templates to synthesize the second plus strand. Essentially two strategies were employed as follows. (i) The 3' ends of the cDNA transcripts were extended by addition of 50 to 100 dAMP residues by terminal deoxynucleotidyl transferase. The (dA)n-tailed cDNA transcripts were used as templates along with an oligomer of dT as primer and Escherichia coli DNA polymerase to synthesize the plus strands. (ii) DNase-digested calf thymus DNA was used to prime the synthesis of plus strands on long cDNA with E. coli DNA polymerase I. In both cases, the synthesis of the plus strands was monitored by increased resistance of the cDNA templates to single-strand-specific S1 nuclease. The double-stranded DNA was fractionated on neutral sucrose gradients. Analysis of the double-stranded DNA synthesized by using oligo(dT) primer showed the plus strands to be about 5 to 6 kb long, whereas the plus strands synthesized by using DNase-digested calf thymus DNA primers were only 0.3 to 0.5 kb long. Double-stranded DNA synthesized by either method has an average size of 6 x 10(6) daltons. Double-stranded DNA was also synthesized by using cDNA transcripts as templates without the addition of any primers. In this case, the plus strands were covalently linked to the template strand and were not representative of the whole parent strand.", "contents": "Genome organization of RNA tumor viruses. I. In vitro synthesis of full-genome-length single-stranded and double-stranded viral DNA transcripts. Genome-length complementary DNA (cDNA) transcripts were synthesized in vitro by using purified virions of avian myeloblastosis virus. Moloney murine leukemia virus, and clone 124 mouse sarcoma virus. The size of the genomelenth cDNA transcripts was measured on either alkaline sucrose gradients or alkaline agarose gels. The longest cDNA transcripts synthesized by using avian myeloblastosis virus, Moloney murine leukemia virus, and clone 124 mouse sarcoma virus were 7, 9 and 6 kilobases (kb), respectively. The in vitro system used was capable of synthesizing double-stranded DNA, but the plus strands (same polarity as the viral RNA) were only 0.5 to 1.5 kb long. Lone Moloney murine leukemia virus cDNA transcripts were used as templates to synthesize the second plus strand. Essentially two strategies were employed as follows. (i) The 3' ends of the cDNA transcripts were extended by addition of 50 to 100 dAMP residues by terminal deoxynucleotidyl transferase. The (dA)n-tailed cDNA transcripts were used as templates along with an oligomer of dT as primer and Escherichia coli DNA polymerase to synthesize the plus strands. (ii) DNase-digested calf thymus DNA was used to prime the synthesis of plus strands on long cDNA with E. coli DNA polymerase I. In both cases, the synthesis of the plus strands was monitored by increased resistance of the cDNA templates to single-strand-specific S1 nuclease. The double-stranded DNA was fractionated on neutral sucrose gradients. Analysis of the double-stranded DNA synthesized by using oligo(dT) primer showed the plus strands to be about 5 to 6 kb long, whereas the plus strands synthesized by using DNase-digested calf thymus DNA primers were only 0.3 to 0.5 kb long. Double-stranded DNA synthesized by either method has an average size of 6 x 10(6) daltons. Double-stranded DNA was also synthesized by using cDNA transcripts as templates without the addition of any primers. In this case, the plus strands were covalently linked to the template strand and were not representative of the whole parent strand."}
{"id": "PMID:209214", "title": "Simian virus 40 DNA extracted from infected cells with sodium deoxycholate no longer reflects its in vivo superhelix density.", "content": "When simian virus 40 DNA is extracted from infected cells with low concentrations of sodium deoxycholate, which selectively extract non-encapsidated simian virus 40 DNA, the DNA has a lower average number of superhelical turns than the DNA extracted from purified viral particles. During extraction, a partial deproteinization of the DNA by a concentration of detergent that did not inactivate a nicking-closing activity led to the removal of some superhelical turns. The DNA extracted in this way no longer reflected its in vivo number of superhelical turns.", "contents": "Simian virus 40 DNA extracted from infected cells with sodium deoxycholate no longer reflects its in vivo superhelix density. When simian virus 40 DNA is extracted from infected cells with low concentrations of sodium deoxycholate, which selectively extract non-encapsidated simian virus 40 DNA, the DNA has a lower average number of superhelical turns than the DNA extracted from purified viral particles. During extraction, a partial deproteinization of the DNA by a concentration of detergent that did not inactivate a nicking-closing activity led to the removal of some superhelical turns. The DNA extracted in this way no longer reflected its in vivo number of superhelical turns."}
{"id": "PMID:209215", "title": "Sequence of protein synthesis in cells infected by human cytomegalovirus: early and late virus-induced polypeptides.", "content": "At least 10 distinct early virus-induced polypeptides were synthesized within 0 to 6 h after infection of permissive cells with cytomegalovirus. These virus-induced polypeptides were synthesized before and independently of viral DNA replication. A majority of these early virus-induced polypeptides were also synthesized in nonpermissive cells, which do not permit viral DNA replication. The virus-induced polypeptides synthesized before viral DNA replication were hypothesized to be nonstructural proteins coded for by the cytomegalovirus genome. Their synthesis was found to be a sequential process, since three proteins preceded the synthesis of the others. Synthesis of all early cytomegalovirus-induced proteins was a transient process; the proteins reached their highest molar ratios before the onset of viral DNA replication. Late viral proteins were synthesized at the time of the onset of viral DNA replication, which was approximately 15 h after infection. Their synthesis was continuous and increased in molar ratios with the accumulation of newly synthesized viral DNA in the cells. The presence of the amino acid analog canavanine or azetadine during the early stage of infection suppressed viral DNA replication. The amount of viral DNA synthesis was directly correlated to the relative amount of late viral protein synthesis. Because synthesis of late viral proteins depended upon viral DNA replication, the proteins were not detected in permissive cells treated with an inhibitor of viral DNA synthesis or in nonpermissive cells that are restrictive for cytomegalovirus DNA replication.", "contents": "Sequence of protein synthesis in cells infected by human cytomegalovirus: early and late virus-induced polypeptides. At least 10 distinct early virus-induced polypeptides were synthesized within 0 to 6 h after infection of permissive cells with cytomegalovirus. These virus-induced polypeptides were synthesized before and independently of viral DNA replication. A majority of these early virus-induced polypeptides were also synthesized in nonpermissive cells, which do not permit viral DNA replication. The virus-induced polypeptides synthesized before viral DNA replication were hypothesized to be nonstructural proteins coded for by the cytomegalovirus genome. Their synthesis was found to be a sequential process, since three proteins preceded the synthesis of the others. Synthesis of all early cytomegalovirus-induced proteins was a transient process; the proteins reached their highest molar ratios before the onset of viral DNA replication. Late viral proteins were synthesized at the time of the onset of viral DNA replication, which was approximately 15 h after infection. Their synthesis was continuous and increased in molar ratios with the accumulation of newly synthesized viral DNA in the cells. The presence of the amino acid analog canavanine or azetadine during the early stage of infection suppressed viral DNA replication. The amount of viral DNA synthesis was directly correlated to the relative amount of late viral protein synthesis. Because synthesis of late viral proteins depended upon viral DNA replication, the proteins were not detected in permissive cells treated with an inhibitor of viral DNA synthesis or in nonpermissive cells that are restrictive for cytomegalovirus DNA replication."}
{"id": "PMID:209216", "title": "Genetic analysis of a cytomegalovirus-like agent isolated from human brain.", "content": "An unusual cytomegalovirus (CMV, strain Colburn) isolated from brain biopsy of a boy with clinical encephalopathy was studied for genetic relatedness to human and simian CMV. Cross-examination of the purified viral DNA by DNA-DNA reassociation kinetics analyses showed more than 90% homology between Colburn virus and simian CMV (strain GR2757) and a lack of detectable homology between Colburn virus and human CMV (strains AD-169 and TW-87). Restriction endonuclease analysis of Colburn DNA showed some similarity of the DNA fragment pattern with that of simian CMV DNA, although the DNA fragment patterns were not identical, and showed no similarity to that of human CMV DNA. The molecular size and density of viral DNA were close to those of simian CMV DNA. The antigenic study, as performed by complement fixation and neutralization tests, showed strong cross-reactivity of Colburn virus to simian GR2757 virus. One-way cross-reaction of Colburn virus to several human CMV isolates (AD-169, Davis, and Town) was detected by complement fixation; this one-way cross-reaction was not obvious in a plaque neutralization test. It was concluded that Colburn is a simian CMV-related virus.", "contents": "Genetic analysis of a cytomegalovirus-like agent isolated from human brain. An unusual cytomegalovirus (CMV, strain Colburn) isolated from brain biopsy of a boy with clinical encephalopathy was studied for genetic relatedness to human and simian CMV. Cross-examination of the purified viral DNA by DNA-DNA reassociation kinetics analyses showed more than 90% homology between Colburn virus and simian CMV (strain GR2757) and a lack of detectable homology between Colburn virus and human CMV (strains AD-169 and TW-87). Restriction endonuclease analysis of Colburn DNA showed some similarity of the DNA fragment pattern with that of simian CMV DNA, although the DNA fragment patterns were not identical, and showed no similarity to that of human CMV DNA. The molecular size and density of viral DNA were close to those of simian CMV DNA. The antigenic study, as performed by complement fixation and neutralization tests, showed strong cross-reactivity of Colburn virus to simian GR2757 virus. One-way cross-reaction of Colburn virus to several human CMV isolates (AD-169, Davis, and Town) was detected by complement fixation; this one-way cross-reaction was not obvious in a plaque neutralization test. It was concluded that Colburn is a simian CMV-related virus."}
{"id": "PMID:209217", "title": "Isolation of the envelope of vesicular stomatitis virus.", "content": "Vesicular stomatitis virus was disrupted by a combination of freezing and thawing, osmotic shock, and sonic treatment. Subviral components were separated by isopycnic centrifugation. The low-density, lipid-rich fractions were pooled and shown to contain primarily viral glycoprotein. Further purification of this material resulted in the isolation of a preparation of vesicles which contained only the G protein and the same phospholipids as in the intact virions and exhibited spikelike structures similar to those on intact vesicular stomatitis virions. We conclude that we have isolated fragments of native vesicular stomatitis virus envelopes.", "contents": "Isolation of the envelope of vesicular stomatitis virus. Vesicular stomatitis virus was disrupted by a combination of freezing and thawing, osmotic shock, and sonic treatment. Subviral components were separated by isopycnic centrifugation. The low-density, lipid-rich fractions were pooled and shown to contain primarily viral glycoprotein. Further purification of this material resulted in the isolation of a preparation of vesicles which contained only the G protein and the same phospholipids as in the intact virions and exhibited spikelike structures similar to those on intact vesicular stomatitis virions. We conclude that we have isolated fragments of native vesicular stomatitis virus envelopes."}
{"id": "PMID:209218", "title": "Peptide analysis of the transformation-specific antigen from avian sarcoma virus-transformed cells.", "content": "Sera from rabbits bearing tumors induced by avian sarcoma virus (ASV) were ussed to immunopecipitate virus-specific proteins from extracts of chicken, hamster, and field vole cells transformed by ASV. Two virus-specific proteins having molecular weights of 76,000 and 60,000 were found in all cell lines examined. The 76,000-molecular-weight protein, Pr76, is the precursor to the internal core proteins of ASV. The 60,000-molecular-weight (60K) transformation-specific antigen from each cell line was subjected to peptide analysis, using chymotrypsin and Staphylococcus aureus V8 protease. The resulting peptide maps of the 60K protein from the different ASV-infected cell types were similar for each enzyme, strongly suggesting that the 60K protein is virus coded. Two-dimensional analysis of chymotryptic peptides from Pr76 and 60K reveals that 60K is not related to the gs antigen precursor. Radiolabeling of ASV-transformed cells with inorganic phosphate revealed that 60K is phosphorylated in vivo. The 60K proteins isolated from both ASV-transformed chicken and field vole cells were found to contain one tryptic phosphopeptide. The tryptic phosphopeptides of 60K from both cell lines migrated identically upon two-dimensional peptide analyses, and their migration differed from that of the principal phosphopeptide of Pr76.", "contents": "Peptide analysis of the transformation-specific antigen from avian sarcoma virus-transformed cells. Sera from rabbits bearing tumors induced by avian sarcoma virus (ASV) were ussed to immunopecipitate virus-specific proteins from extracts of chicken, hamster, and field vole cells transformed by ASV. Two virus-specific proteins having molecular weights of 76,000 and 60,000 were found in all cell lines examined. The 76,000-molecular-weight protein, Pr76, is the precursor to the internal core proteins of ASV. The 60,000-molecular-weight (60K) transformation-specific antigen from each cell line was subjected to peptide analysis, using chymotrypsin and Staphylococcus aureus V8 protease. The resulting peptide maps of the 60K protein from the different ASV-infected cell types were similar for each enzyme, strongly suggesting that the 60K protein is virus coded. Two-dimensional analysis of chymotryptic peptides from Pr76 and 60K reveals that 60K is not related to the gs antigen precursor. Radiolabeling of ASV-transformed cells with inorganic phosphate revealed that 60K is phosphorylated in vivo. The 60K proteins isolated from both ASV-transformed chicken and field vole cells were found to contain one tryptic phosphopeptide. The tryptic phosphopeptides of 60K from both cell lines migrated identically upon two-dimensional peptide analyses, and their migration differed from that of the principal phosphopeptide of Pr76."}
{"id": "PMID:209219", "title": "Human cytomegalovirus DNA. I. Molecular weight and infectivity.", "content": "Human cytomegalovirus DNA (strain AD 169) 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 +/- 5.22 micron, corresponding to a molecular weight of 147 +/- 6.2 x 10(6). The DNA was infectious when tested in human embryonic lung cells.", "contents": "Human cytomegalovirus DNA. I. Molecular weight and infectivity. Human cytomegalovirus DNA (strain AD 169) 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 +/- 5.22 micron, corresponding to a molecular weight of 147 +/- 6.2 x 10(6). The DNA was infectious when tested in human embryonic lung cells."}
{"id": "PMID:209220", "title": "Anomalous behavior of the major avian myeloblastosis virus glycoprotein in the presence of sodium dodecyl sulfate.", "content": "The sodium dodecyl sulfate (SDS) complex of the major glycoprotein of avian myeloblastosis virus exhibited an anomalously low free electrophoretic mobility compared with those of non-glycosylated protein standards. The apparent molecular weight of the glycoprotein calculated from the relation between log molecular weight and electrophoretic mobility depended on the acrylamide concentration and reached a lower limit of 80,000. The molecular weight was also estimated from the retardation coefficients of protein standards and the viral glycoprotein. This method yielded a molecular weight of 64,000 for the avian myeloblastosis virus glycoprotein. When gel chromatography in SDS was used to determine the apparent molecular weight of the glycoprotein from its hydrodynamic properties alone, the estimated value was 50,000. The generally assigned value of 80,000 daltons for the avian myeloblastosis virus major glycoprotein, as determined by SDS electrophoresis, may be an overestimate due to its relatively low free electrophoretic mobility and peculiar conformation in SDS.", "contents": "Anomalous behavior of the major avian myeloblastosis virus glycoprotein in the presence of sodium dodecyl sulfate. The sodium dodecyl sulfate (SDS) complex of the major glycoprotein of avian myeloblastosis virus exhibited an anomalously low free electrophoretic mobility compared with those of non-glycosylated protein standards. The apparent molecular weight of the glycoprotein calculated from the relation between log molecular weight and electrophoretic mobility depended on the acrylamide concentration and reached a lower limit of 80,000. The molecular weight was also estimated from the retardation coefficients of protein standards and the viral glycoprotein. This method yielded a molecular weight of 64,000 for the avian myeloblastosis virus glycoprotein. When gel chromatography in SDS was used to determine the apparent molecular weight of the glycoprotein from its hydrodynamic properties alone, the estimated value was 50,000. The generally assigned value of 80,000 daltons for the avian myeloblastosis virus major glycoprotein, as determined by SDS electrophoresis, may be an overestimate due to its relatively low free electrophoretic mobility and peculiar conformation in SDS."}
{"id": "PMID:209222", "title": "Renal tumors involving the inferior vena cava: plan for management.", "content": "Our experience in the management of 12 malignant renal tumors involving the inferior vena cava is analyzed and a plan to manage the different degrees of caval involvement is discussed. The use of Pringle maneuver to control hepatic circulation during removal of suprahepatic caval extensions is recommended. Followup to date supports aggressive operative management in these patients.", "contents": "Renal tumors involving the inferior vena cava: plan for management. Our experience in the management of 12 malignant renal tumors involving the inferior vena cava is analyzed and a plan to manage the different degrees of caval involvement is discussed. The use of Pringle maneuver to control hepatic circulation during removal of suprahepatic caval extensions is recommended. Followup to date supports aggressive operative management in these patients."}
{"id": "PMID:209223", "title": "Surgical considerations in treatment of intraductal carcinoma of the prostate.", "content": "Intraductal carcinomas of the prostate comprise about 3 per cent of all prostatic carcinomas and constitute a heterogeneous group of tumors that include 1) transitional or squamous cell carcinoma, 2) intraductal adenocarcinoma, 3) endometrioid carcinoma and 4) mixed ductal carcinoma. Generally, these tumors are poorly responsive to endocrine and radiation therapy, and complete surgical excision offers the best chance for long-term survival. A case of intraductal adenocarcinoma is presented that illustrates many of the features of these tumors.", "contents": "Surgical considerations in treatment of intraductal carcinoma of the prostate. Intraductal carcinomas of the prostate comprise about 3 per cent of all prostatic carcinomas and constitute a heterogeneous group of tumors that include 1) transitional or squamous cell carcinoma, 2) intraductal adenocarcinoma, 3) endometrioid carcinoma and 4) mixed ductal carcinoma. Generally, these tumors are poorly responsive to endocrine and radiation therapy, and complete surgical excision offers the best chance for long-term survival. A case of intraductal adenocarcinoma is presented that illustrates many of the features of these tumors."}
{"id": "PMID:209225", "title": "Gallium scans for staging small cell lung cancer.", "content": "The high incidence of gallium 67 accumulation in lung cencer has made radioistope scanning with this agent useful in identifying the extent of cancer locally. However, we investigated the usefulness of whole-body gallium 67 scanning, compared with physical examination, bone, liver and brain scans, and bone marrow aspirate and biopsy, in detecting metastases outside the chest in 47 patients with small cell lung cancer. In each case whole-body scanning with gallium 67 was inferior to the other methods used to detect extrathoracic tumor deposits.", "contents": "Gallium scans for staging small cell lung cancer. The high incidence of gallium 67 accumulation in lung cencer has made radioistope scanning with this agent useful in identifying the extent of cancer locally. However, we investigated the usefulness of whole-body gallium 67 scanning, compared with physical examination, bone, liver and brain scans, and bone marrow aspirate and biopsy, in detecting metastases outside the chest in 47 patients with small cell lung cancer. In each case whole-body scanning with gallium 67 was inferior to the other methods used to detect extrathoracic tumor deposits."}
{"id": "PMID:209229", "title": "Establishment of cultured cell lines derived from a human gastric carcinoma.", "content": "A human gastric carcinoma cell line, KATO-II, and its subline, KATO-III, have been established in vitro from a pleural effusion of a 55-year-old male patient. Kato-II cells have been maintained using a culture medium containing human cord serum and KATO-III cells have been cultured with a medium containing fetal bovine serum. Both cell lines are morphologically quite similar; they grow in vitro floating free and have cytological features of signet ring cells. Population doubling times for KATO-II and KATO-III were 74 hours and 36 hours, repsectively. The modal chromosomal numbers of these cell lines fell in a tetraploid range. Heterotransplantation of KATO-II and KATO-III cells was successfully done in the cheek pouches of antithymocyte serum-treated hamsters. Microscopical appearance of the resultant tumors was consistent with poorly-differentiated adenocarcinoma comparable to the original tumor.", "contents": "Establishment of cultured cell lines derived from a human gastric carcinoma. A human gastric carcinoma cell line, KATO-II, and its subline, KATO-III, have been established in vitro from a pleural effusion of a 55-year-old male patient. Kato-II cells have been maintained using a culture medium containing human cord serum and KATO-III cells have been cultured with a medium containing fetal bovine serum. Both cell lines are morphologically quite similar; they grow in vitro floating free and have cytological features of signet ring cells. Population doubling times for KATO-II and KATO-III were 74 hours and 36 hours, repsectively. The modal chromosomal numbers of these cell lines fell in a tetraploid range. Heterotransplantation of KATO-II and KATO-III cells was successfully done in the cheek pouches of antithymocyte serum-treated hamsters. Microscopical appearance of the resultant tumors was consistent with poorly-differentiated adenocarcinoma comparable to the original tumor."}
{"id": "PMID:209231", "title": "[Aspects of enzymatic toxicology of metals. A review (author's transl)].", "content": "The adverse and beneficial effects of metals have occupied a great concern in many branches of biology for centuries, but their biochemical roles have been studied systematically only in the last four decades. Almost all the metals, especially those of high toxicity, bind readily to mercapto groups, and these are frequently important in enzyme systems. Furthermore, a large number of in vitro and in vivo studies have shown that toxic metals can replace essential metals in many of their metalloenzymes, with resultant changes in activity. Metals also bind to protein, phospholipid and nucleic acid, and have been shown to effect a change in the conformation of enzymes required for normal function, or to uncouple oxidative phosphorylation. This review, of necessity brief, will focus on the biochemical and enzymatic effects of metals, emphasizing meanings available to occupational medicine. The present knowledge on enzymatic toxicology of metals can provide for access to three main problems. These include an exposure evaluation, a health injury evaluation and a pathogenic understanding of workers exposed to metals. In this article, these problems are discussed in general, and the recent developments made in the enzymatic toxicology of cadmium and lead are presented with pertinent literatures.", "contents": "[Aspects of enzymatic toxicology of metals. A review (author's transl)]. The adverse and beneficial effects of metals have occupied a great concern in many branches of biology for centuries, but their biochemical roles have been studied systematically only in the last four decades. Almost all the metals, especially those of high toxicity, bind readily to mercapto groups, and these are frequently important in enzyme systems. Furthermore, a large number of in vitro and in vivo studies have shown that toxic metals can replace essential metals in many of their metalloenzymes, with resultant changes in activity. Metals also bind to protein, phospholipid and nucleic acid, and have been shown to effect a change in the conformation of enzymes required for normal function, or to uncouple oxidative phosphorylation. This review, of necessity brief, will focus on the biochemical and enzymatic effects of metals, emphasizing meanings available to occupational medicine. The present knowledge on enzymatic toxicology of metals can provide for access to three main problems. These include an exposure evaluation, a health injury evaluation and a pathogenic understanding of workers exposed to metals. In this article, these problems are discussed in general, and the recent developments made in the enzymatic toxicology of cadmium and lead are presented with pertinent literatures."}
{"id": "PMID:209238", "title": "Familial hypercholesterolemia: pathogenesis of a receptor disease.", "content": "Familial hypercholesterolemia is a prototype for a class of diseases that result from defects in receptor molecules. The three cardinal features of familial hypercholesterolemia are: 1) a selective elevation in the plasma level of one cholesterol-carrying lipoprotein, low density lipoprotein (LDL); 2) a selective deposition of LDL-derived cholesterol in macrophage-like scavenger cells throughout the body, but not in parenchymal cells; and 3) inheritance as an autosomal dominant trait with gene dosage effect, i.e., the disease is more serious in patients with the homozygous than with the heterozygous state. In this article, we review the evidence that each of these cardinal features of familial hypercholesterolemia can be explained by a genetic defect in a cell surface receptor for plasma LDL.", "contents": "Familial hypercholesterolemia: pathogenesis of a receptor disease. Familial hypercholesterolemia is a prototype for a class of diseases that result from defects in receptor molecules. The three cardinal features of familial hypercholesterolemia are: 1) a selective elevation in the plasma level of one cholesterol-carrying lipoprotein, low density lipoprotein (LDL); 2) a selective deposition of LDL-derived cholesterol in macrophage-like scavenger cells throughout the body, but not in parenchymal cells; and 3) inheritance as an autosomal dominant trait with gene dosage effect, i.e., the disease is more serious in patients with the homozygous than with the heterozygous state. In this article, we review the evidence that each of these cardinal features of familial hypercholesterolemia can be explained by a genetic defect in a cell surface receptor for plasma LDL."}
{"id": "PMID:209240", "title": "[New approaches to the evaluation of the cholesterol content of plasma lipoprotein fractions in normo- and hyperlipoproteinemias].", "content": "The examination of 1073 males ranging in age from 40 to 59 living in Moscow and Leningrad, and of 146 patients with ischemic heart disease showed a decrease in the alpha-lipoprotein cholesterol level and an increase in the cholesterol content of atherogenic fractions (beta- and pre-beta-lipoproteins) in individuals with ischemic heart disease in the absence of hyperlipoproteinemia (HLP). In combination of ischemic heart disease with hyperlipoproteinemia these changes are pronounced to a larger degree. From the analysis of the results of the studies it is suggested that the coefficient (see article) is determined to reveal disorders in lipoprotein metabolism particularly in the absence of hyperlipoproteinemia. This coefficient is significantly higher in individuals with ischemic heart disease and no hyperlipoproteinemia than in healthy males of the same age group; its value is highest in ischemic disease with hyperlipoproteinemia.", "contents": "[New approaches to the evaluation of the cholesterol content of plasma lipoprotein fractions in normo- and hyperlipoproteinemias]. The examination of 1073 males ranging in age from 40 to 59 living in Moscow and Leningrad, and of 146 patients with ischemic heart disease showed a decrease in the alpha-lipoprotein cholesterol level and an increase in the cholesterol content of atherogenic fractions (beta- and pre-beta-lipoproteins) in individuals with ischemic heart disease in the absence of hyperlipoproteinemia (HLP). In combination of ischemic heart disease with hyperlipoproteinemia these changes are pronounced to a larger degree. From the analysis of the results of the studies it is suggested that the coefficient (see article) is determined to reveal disorders in lipoprotein metabolism particularly in the absence of hyperlipoproteinemia. This coefficient is significantly higher in individuals with ischemic heart disease and no hyperlipoproteinemia than in healthy males of the same age group; its value is highest in ischemic disease with hyperlipoproteinemia."}
{"id": "PMID:209243", "title": "[The disease pattern of the diffuse, nesidioblastic hyperplasia of the pancreatic islets in newborn and infants (author's transl)].", "content": "The course of illness of a male infant who lived for seven months with a diffuse, nesidioblastic hyperplasia of pancreatic islets is described. Before surgical intervention the diagnosis should be ascertained by 1. observation of acetonuria which is always absent after hypoglycemic episodes, 2, the typical constellation of insulin concentration, free fatty acid concentration and beta-hydroxybutyrat during a hypoglycemia (as found by Baker et al. 1976) and/or by simultaneous measuring of glucose-insulin levels under the conditions of fasting as well as of oral leucine, oral glucose and intravenous tolbutamide loading. Therapy with diazoxide should be tried in any case. If all conservative measure fail and relative or absolute hyperinsulinemia is proved, experience shows that an immediate operation is indicated.", "contents": "[The disease pattern of the diffuse, nesidioblastic hyperplasia of the pancreatic islets in newborn and infants (author's transl)]. The course of illness of a male infant who lived for seven months with a diffuse, nesidioblastic hyperplasia of pancreatic islets is described. Before surgical intervention the diagnosis should be ascertained by 1. observation of acetonuria which is always absent after hypoglycemic episodes, 2, the typical constellation of insulin concentration, free fatty acid concentration and beta-hydroxybutyrat during a hypoglycemia (as found by Baker et al. 1976) and/or by simultaneous measuring of glucose-insulin levels under the conditions of fasting as well as of oral leucine, oral glucose and intravenous tolbutamide loading. Therapy with diazoxide should be tried in any case. If all conservative measure fail and relative or absolute hyperinsulinemia is proved, experience shows that an immediate operation is indicated."}
{"id": "PMID:209244", "title": "[New aspects of catecholamin-receptor interactions. Pathophysiological and clinical implications (author's transl)].", "content": "The molecular aspects of catecholamine-receptor interactions are reviewed with respect to their clinical implications. Beta- and in some tissues alpha-adrenergic receptors are coupled to the membrane-bound adenylate cyclase. The adrenergic receptor sites are distinct membrane constituents. Their number and the ratio alpha-to beta-receptor site depend on the plasma concentration of catecholamines and are affected by diet and endocrinological factors. Recent clinical studies suggest that long-term treatment with beta-adrenergic agonists may induces desensitization of target tissues due to changes in the adrenergic receptor moieties.", "contents": "[New aspects of catecholamin-receptor interactions. Pathophysiological and clinical implications (author's transl)]. The molecular aspects of catecholamine-receptor interactions are reviewed with respect to their clinical implications. Beta- and in some tissues alpha-adrenergic receptors are coupled to the membrane-bound adenylate cyclase. The adrenergic receptor sites are distinct membrane constituents. Their number and the ratio alpha-to beta-receptor site depend on the plasma concentration of catecholamines and are affected by diet and endocrinological factors. Recent clinical studies suggest that long-term treatment with beta-adrenergic agonists may induces desensitization of target tissues due to changes in the adrenergic receptor moieties."}
{"id": "PMID:209245", "title": "Responsiveness of plasma aldosterone: dependency upon basal secretory activity.", "content": "The responsiveness of plasma aldosterone levels to various stimuli was evaluated in 44 normal subjects, 17 patients with mild to moderate renal failure, 30 patients with terminal renal failure, and 13 anephric subjects. Plasma aldosterone, renin activity (PRA), cortisol, sodium, and potassium levels were measured before and after one hour of upright posture (N = 191); ACTH infusions (N = 76); and angiotensin II infusion (N = 36). Plasma aldosterone responses correlated (r greater than or equal to 0.53; p less than 0.02) with basal plasma aldosterone levels during upright posture in all four groups, with ACTH infusion in all groups except anephric subjects, and with angiotensin II administration in patients with mild to moderate renal failure or patients combined. These relationships were consistently closer than those between aldosterone responses and changes in PRA or basal PRA. However, postural aldosterone responsiveness at any given basal aldosterone level was significantly lower in patients with renal disease than in normal subjects, and this was associated with a parallel impairment in renin responsiveness. In contrast, when related to basal levels aldosterone responsiveness to ACTH or angiotensin II appreared to be comparable in normal subjects and patients with renal disease. Aldosterone responses to posture, ACTH, or angiotensin II did not correlate with associated changes in plasma cortisol, sodium, or potassium levels. These data suggest that basal adrenal secretory activity is a major factor conditioning aldosterone responsiveness to various stimuli in normal subjects as well as in patients with renal disease.", "contents": "Responsiveness of plasma aldosterone: dependency upon basal secretory activity. The responsiveness of plasma aldosterone levels to various stimuli was evaluated in 44 normal subjects, 17 patients with mild to moderate renal failure, 30 patients with terminal renal failure, and 13 anephric subjects. Plasma aldosterone, renin activity (PRA), cortisol, sodium, and potassium levels were measured before and after one hour of upright posture (N = 191); ACTH infusions (N = 76); and angiotensin II infusion (N = 36). Plasma aldosterone responses correlated (r greater than or equal to 0.53; p less than 0.02) with basal plasma aldosterone levels during upright posture in all four groups, with ACTH infusion in all groups except anephric subjects, and with angiotensin II administration in patients with mild to moderate renal failure or patients combined. These relationships were consistently closer than those between aldosterone responses and changes in PRA or basal PRA. However, postural aldosterone responsiveness at any given basal aldosterone level was significantly lower in patients with renal disease than in normal subjects, and this was associated with a parallel impairment in renin responsiveness. In contrast, when related to basal levels aldosterone responsiveness to ACTH or angiotensin II appreared to be comparable in normal subjects and patients with renal disease. Aldosterone responses to posture, ACTH, or angiotensin II did not correlate with associated changes in plasma cortisol, sodium, or potassium levels. These data suggest that basal adrenal secretory activity is a major factor conditioning aldosterone responsiveness to various stimuli in normal subjects as well as in patients with renal disease."}
{"id": "PMID:209263", "title": "Oral hydration rotavirus diarrhoea: a double blind comparison of sucrose with glucose electrolyte solution.", "content": "Of 57 male children, aged 5 months to 2 1/2 years with rotavirus diarrhoea, 28 were given oral therapy with sucrose electrolyte solution and 29 were given glucose electrolyte solution in a randomised double-blind trial. All were rehydrated and remained so on oral therapy alone. These patients were compared with 44 children, also with rotavirus, who were treated only with intravenous hydration. The oral therapy and intravenous therapy groups did not differ clinically in the rate of rehydration or the rate of purging. Vomiting did not prevent the giving of oral therapy during hospital admission. Bangladeshi children with rotavirus diarrhoea have a defect of carbohydrate digestion but this defect does not prevent the use of a sugar electrolyte solution for oral hydration.", "contents": "Oral hydration rotavirus diarrhoea: a double blind comparison of sucrose with glucose electrolyte solution. Of 57 male children, aged 5 months to 2 1/2 years with rotavirus diarrhoea, 28 were given oral therapy with sucrose electrolyte solution and 29 were given glucose electrolyte solution in a randomised double-blind trial. All were rehydrated and remained so on oral therapy alone. These patients were compared with 44 children, also with rotavirus, who were treated only with intravenous hydration. The oral therapy and intravenous therapy groups did not differ clinically in the rate of rehydration or the rate of purging. Vomiting did not prevent the giving of oral therapy during hospital admission. Bangladeshi children with rotavirus diarrhoea have a defect of carbohydrate digestion but this defect does not prevent the use of a sugar electrolyte solution for oral hydration."}
{"id": "PMID:209265", "title": "Nasopharyngeal angiofibroma: a twenty year study.", "content": "A control rate of approximately 80% has been obtained in 45 cases of juvenile nasopharyngeal angiofibroma treated by a single moderate dose of radiotherapy at the Princess Margaret Hospital, Toronto. The remaining patients ultimately achieved control generally after further irradiation. Immediate side-effects of the treatment have been minimal, and no late complications have been observed. In 2-20 years' follow-up, no irradiation-induced tumors have been found. Superiority of irradiation in these cases over surgery is emphasized, as well as the importance of using sophisticated techniques to limit the volume of tissues irradiated and protect vulnerable radiosenstitive structures. Because tumor regression can be expected to continue for many months after treatment has been completed, a policy of observation following radiotherapy is recommended.", "contents": "Nasopharyngeal angiofibroma: a twenty year study. A control rate of approximately 80% has been obtained in 45 cases of juvenile nasopharyngeal angiofibroma treated by a single moderate dose of radiotherapy at the Princess Margaret Hospital, Toronto. The remaining patients ultimately achieved control generally after further irradiation. Immediate side-effects of the treatment have been minimal, and no late complications have been observed. In 2-20 years' follow-up, no irradiation-induced tumors have been found. Superiority of irradiation in these cases over surgery is emphasized, as well as the importance of using sophisticated techniques to limit the volume of tissues irradiated and protect vulnerable radiosenstitive structures. Because tumor regression can be expected to continue for many months after treatment has been completed, a policy of observation following radiotherapy is recommended."}
{"id": "PMID:209266", "title": "Recurrent laryngeal nerve pathology in spasmodic dysphonia.", "content": "Since it was first described in 1871, spasmodic (spastic) dysphonia has been considered a disease of psychogenic origin. Unsupported theories of possible organic etiology have appeared sporadically in the literature. In 1976 sectioning of the recurrent laryngeal nerve for patients with this disease was reported with resultant improvement in voice production. This was attempted because the spasmodic dysphonic has, in effect, already compensated vocal cords bilaterally. It was reasoned, therefore, that if one of these was paralyzed the patient would immediately be converted to a state approximating that of well-compensated unilateral vocal cord paralysis which situation, as is well known, usually carries with it a fairly good voice. A controlled study to evaluate the efficacy of this surgical approach has been undertaken at the Cleveland Clinic during the past year. In an attempt to elucidate the possible organic etiology of spasmodic dysphonia, a section of nerve was removed in every case and examined by both light and electron microscopy. Special stains for myelin were also used on the light microscopy specimens. Demyelinization has been found in most of the cases examined by electron microscopy. Possible correlation between this disease entity and other cranial nerve syndromes of unknown etiology is noted. Such conditions as trigeminal neuralgia, glossopharyngeal neuralgia, belpharospasm, hemifacial spasm, and even possibly Bell's palsy may exhibit a similar etiology.", "contents": "Recurrent laryngeal nerve pathology in spasmodic dysphonia. Since it was first described in 1871, spasmodic (spastic) dysphonia has been considered a disease of psychogenic origin. Unsupported theories of possible organic etiology have appeared sporadically in the literature. In 1976 sectioning of the recurrent laryngeal nerve for patients with this disease was reported with resultant improvement in voice production. This was attempted because the spasmodic dysphonic has, in effect, already compensated vocal cords bilaterally. It was reasoned, therefore, that if one of these was paralyzed the patient would immediately be converted to a state approximating that of well-compensated unilateral vocal cord paralysis which situation, as is well known, usually carries with it a fairly good voice. A controlled study to evaluate the efficacy of this surgical approach has been undertaken at the Cleveland Clinic during the past year. In an attempt to elucidate the possible organic etiology of spasmodic dysphonia, a section of nerve was removed in every case and examined by both light and electron microscopy. Special stains for myelin were also used on the light microscopy specimens. Demyelinization has been found in most of the cases examined by electron microscopy. Possible correlation between this disease entity and other cranial nerve syndromes of unknown etiology is noted. Such conditions as trigeminal neuralgia, glossopharyngeal neuralgia, belpharospasm, hemifacial spasm, and even possibly Bell's palsy may exhibit a similar etiology."}
{"id": "PMID:209281", "title": "Neural factors in experimental degenerative arteriopathy.", "content": "Intermittent electrical stimulation of the lateral hypothalamus of rats performed for 30 min to 6 hr, results in hyperlipidemia and endothelial cell damage of the aorta and coronary arteries. Hyperlipidemia is related to transient biliary obstruction elicited by hypothalamic stimulation and is characterized by elevation of the cholesterol, phospholipid, and triglyceride fractions. Endothelial cell damage is observed ultrastructurally as plasma membrane degeneration with detachment and the formation of large spaces (\"vacuoles\"). Thus, neural factors may be implicated in inducing conditions associated with early atherogenesis. Stimulation carried out for longer time intervals would be expected to produce more advanced lesions. However, the role of neural transmission per se (i.e., without hyperlipidemia) in producing arteriopathy is not clearly defined from these experiments. In rats, the lesser splanchnic nerve forms the major innervation of the abdominal aorta. In animals fed normal diets, chronic intermittent stimulation of this nerve (up to 3 weeks) resulted in advanced arteriosclerotic changes with intimal fibrosis and calcification. On histologic examination, lipid deposits appeared to be absent from these lesions. Animals stimulated for shorter periods of time exhibited earlier changes associated with atherogenesis, such as endothelial damage, elastic reduplication, and adherent microthrombi. Thus, direct neural transmission, especially if excessive, plays a role in producing arteriopathy. Hyperlipidemia, if persistent, could modify these lesions so that they would accumulate plasma lipids. Experiments to test this hypothesis are currently in progress.", "contents": "Neural factors in experimental degenerative arteriopathy. Intermittent electrical stimulation of the lateral hypothalamus of rats performed for 30 min to 6 hr, results in hyperlipidemia and endothelial cell damage of the aorta and coronary arteries. Hyperlipidemia is related to transient biliary obstruction elicited by hypothalamic stimulation and is characterized by elevation of the cholesterol, phospholipid, and triglyceride fractions. Endothelial cell damage is observed ultrastructurally as plasma membrane degeneration with detachment and the formation of large spaces (\"vacuoles\"). Thus, neural factors may be implicated in inducing conditions associated with early atherogenesis. Stimulation carried out for longer time intervals would be expected to produce more advanced lesions. However, the role of neural transmission per se (i.e., without hyperlipidemia) in producing arteriopathy is not clearly defined from these experiments. In rats, the lesser splanchnic nerve forms the major innervation of the abdominal aorta. In animals fed normal diets, chronic intermittent stimulation of this nerve (up to 3 weeks) resulted in advanced arteriosclerotic changes with intimal fibrosis and calcification. On histologic examination, lipid deposits appeared to be absent from these lesions. Animals stimulated for shorter periods of time exhibited earlier changes associated with atherogenesis, such as endothelial damage, elastic reduplication, and adherent microthrombi. Thus, direct neural transmission, especially if excessive, plays a role in producing arteriopathy. Hyperlipidemia, if persistent, could modify these lesions so that they would accumulate plasma lipids. Experiments to test this hypothesis are currently in progress."}
{"id": "PMID:209282", "title": "The distribution of dietary plant sterols in serum lipoproteins and liver subcellular fractions of rats.", "content": "Rats were fed plant sterols containing campesterol and beta-sitosterol in the differerent proportions, and their distribution in serum lipoproteins and in liver subcellular fractions was determined. In serum lipoproteins, the percentage as well as the concentration of plant sterols increased with the increase in the density of lipoproteins. Thus, high density lipoprotein (HDL) contained the highest and very low density lipoprotein (VLDL), the lowest. Also, there were distinct differences in the ratio of campesterol to sitosterol among lipoproteins, it was the highest in VLDL and lowest in HDL. Quantitatively, more than 75% of campesterol and 80% of sitosterol were carried in HDL; the values were significantly different from those of cholesterol (ca. 70%) in relation to total cholesterol. The distribution of plant sterols in liver subcellular fractions was virtually the same with that of cholesterol. Both nuclei and microsomes contained approximately 40% of total plant sterols.", "contents": "The distribution of dietary plant sterols in serum lipoproteins and liver subcellular fractions of rats. Rats were fed plant sterols containing campesterol and beta-sitosterol in the differerent proportions, and their distribution in serum lipoproteins and in liver subcellular fractions was determined. In serum lipoproteins, the percentage as well as the concentration of plant sterols increased with the increase in the density of lipoproteins. Thus, high density lipoprotein (HDL) contained the highest and very low density lipoprotein (VLDL), the lowest. Also, there were distinct differences in the ratio of campesterol to sitosterol among lipoproteins, it was the highest in VLDL and lowest in HDL. Quantitatively, more than 75% of campesterol and 80% of sitosterol were carried in HDL; the values were significantly different from those of cholesterol (ca. 70%) in relation to total cholesterol. The distribution of plant sterols in liver subcellular fractions was virtually the same with that of cholesterol. Both nuclei and microsomes contained approximately 40% of total plant sterols."}
{"id": "PMID:209286", "title": "Effect of phentolamine on the somatostatin-induced inhibition of glucagon and insulin secretion.", "content": "Synthetic cyclic somatostatin was infused into either the cranial pancreaticoduodenal artery or the femoral vein of anesthetized dogs with or without previous administration of phentolamine. Somatostatin infused into the pancreatic artery at a dose of 50 ng/kg/min for 10 min caused significant decreases in blood flow and plasma basal concentrations of both glucagon and insulin in the cranial pancreaticoduodenal vein, resulting in a profound decline of bihormonal output during the infusion. Arterial plasma glucose was not reduced during the administration of somatostatin in the pancreatic artery. These somatostatin-induced decreases failed to be eliminated by a 0.2 mg/kg injection of phentolamine into the femoral vein followed by a 9-min infusion of this alpha-adrenergic blocker (0.02 mg/kg/min) into the pancreatic artery immediately prior to the somatostatin administration. An inhibition of glucagon and insulin output and a fall of plasma glucose caused by somatostatin (1.7 microgram/min) infused into the femoral vein for 30 min also were not abolished by a prolonged and simultaneous infusion of phentolamine (0.2 mg/min) into the femoral vein over a period of 2 hr. These results indicate that alpha-adrenergic receptor mechanisms do not play a major role in the inhibition of islet glucagon and insulin secretion by somatostatin.", "contents": "Effect of phentolamine on the somatostatin-induced inhibition of glucagon and insulin secretion. Synthetic cyclic somatostatin was infused into either the cranial pancreaticoduodenal artery or the femoral vein of anesthetized dogs with or without previous administration of phentolamine. Somatostatin infused into the pancreatic artery at a dose of 50 ng/kg/min for 10 min caused significant decreases in blood flow and plasma basal concentrations of both glucagon and insulin in the cranial pancreaticoduodenal vein, resulting in a profound decline of bihormonal output during the infusion. Arterial plasma glucose was not reduced during the administration of somatostatin in the pancreatic artery. These somatostatin-induced decreases failed to be eliminated by a 0.2 mg/kg injection of phentolamine into the femoral vein followed by a 9-min infusion of this alpha-adrenergic blocker (0.02 mg/kg/min) into the pancreatic artery immediately prior to the somatostatin administration. An inhibition of glucagon and insulin output and a fall of plasma glucose caused by somatostatin (1.7 microgram/min) infused into the femoral vein for 30 min also were not abolished by a prolonged and simultaneous infusion of phentolamine (0.2 mg/min) into the femoral vein over a period of 2 hr. These results indicate that alpha-adrenergic receptor mechanisms do not play a major role in the inhibition of islet glucagon and insulin secretion by somatostatin."}
{"id": "PMID:209291", "title": "Establishment of a persistent measles virus infection in HEp-2 cells.", "content": "A productive measles virus persistent infection has been established in HEp-2 cells. Greater than 90% of the persistently infected HEp-2 cells (H2MV) exhibited measles specific immunofluorescence and haemadsorption. Although most of the H2MV cells contained measles specific antigens, only a small percentage (less than 1%) actually produced infectious measles virus as determined by infectious centre assays. The measles virus produced by H2MV cells exhibited properties different from the initiating parent Edmonston strain virus, being reduced in virulence and also temperature sensitive for replication at 39 degrees C. The role of these altered virus properties in the establishment of persistence is considered.", "contents": "Establishment of a persistent measles virus infection in HEp-2 cells. A productive measles virus persistent infection has been established in HEp-2 cells. Greater than 90% of the persistently infected HEp-2 cells (H2MV) exhibited measles specific immunofluorescence and haemadsorption. Although most of the H2MV cells contained measles specific antigens, only a small percentage (less than 1%) actually produced infectious measles virus as determined by infectious centre assays. The measles virus produced by H2MV cells exhibited properties different from the initiating parent Edmonston strain virus, being reduced in virulence and also temperature sensitive for replication at 39 degrees C. The role of these altered virus properties in the establishment of persistence is considered."}
{"id": "PMID:209293", "title": "Common antigen between coxsackievirus A 16 and enterovirus 71.", "content": "Cross immunofluorescence revealed that coxsackievirus A 16 (CA 16) shared a common antigen with enterovirus 71 (E 71). The cross reactivity of these two serotypes was also examined by complement fixation test with purified virus preparations fractionated by sucrose density gradient centrifugation and two peaks of antigenicity were detected, one being type-specific and the other cross-reacting. The common antigen was heat-stable and attributable to empty capsids. Immuno-diffusion also revealed the common antigen. Infants without antibody to E 71 developed complement fixing and precipitin antibody to E 71 after recovery from hand, foot and mouth disease caused by CA 16.", "contents": "Common antigen between coxsackievirus A 16 and enterovirus 71. Cross immunofluorescence revealed that coxsackievirus A 16 (CA 16) shared a common antigen with enterovirus 71 (E 71). The cross reactivity of these two serotypes was also examined by complement fixation test with purified virus preparations fractionated by sucrose density gradient centrifugation and two peaks of antigenicity were detected, one being type-specific and the other cross-reacting. The common antigen was heat-stable and attributable to empty capsids. Immuno-diffusion also revealed the common antigen. Infants without antibody to E 71 developed complement fixing and precipitin antibody to E 71 after recovery from hand, foot and mouth disease caused by CA 16."}
{"id": "PMID:209295", "title": "Protective effect of an oral infection with herpes simplex virus type 1 against subsequent genital infection with herpes simplex virus type 2.", "content": "The problem of whether oral Herpes simplex virus type 1 (HSV-1) infection provides protection against subsequent genital infection by Herpes simplex virus type 2 (HSV-2) was investigated. Mice were used as models. Following conditions in man, both the oral and genital infections applied were noninjurious. Mice infected orally with HSV-1 were weakly protected against virus 'take' following vaginal challenge with HSV-2. Genital 'takes' were found in 67% of the immunized mice, as compared with 83% of the controls (protection rate 20%, P = 0.002). The course of genital infection in the immunized mice, however, was relatively mild: Lethality decreased from 97% in the controls to 35% in the immunized mice (protection rate 63%, P less than 0.001). Furthermore, local and neurologic symptoms occurred less frequently. Attempts to isolate the virus from homogenized brain and spinal cord of immunized mice that died after genital challenge with HSV-2 failed in most cases. Also virus could not be recovered from the liver of infected mice, irrespective of the experimental group.", "contents": "Protective effect of an oral infection with herpes simplex virus type 1 against subsequent genital infection with herpes simplex virus type 2. The problem of whether oral Herpes simplex virus type 1 (HSV-1) infection provides protection against subsequent genital infection by Herpes simplex virus type 2 (HSV-2) was investigated. Mice were used as models. Following conditions in man, both the oral and genital infections applied were noninjurious. Mice infected orally with HSV-1 were weakly protected against virus 'take' following vaginal challenge with HSV-2. Genital 'takes' were found in 67% of the immunized mice, as compared with 83% of the controls (protection rate 20%, P = 0.002). The course of genital infection in the immunized mice, however, was relatively mild: Lethality decreased from 97% in the controls to 35% in the immunized mice (protection rate 63%, P less than 0.001). Furthermore, local and neurologic symptoms occurred less frequently. Attempts to isolate the virus from homogenized brain and spinal cord of immunized mice that died after genital challenge with HSV-2 failed in most cases. Also virus could not be recovered from the liver of infected mice, irrespective of the experimental group."}
{"id": "PMID:209296", "title": "BK virus: I. Seroepidemiologic studies and serologic response to viral infection.", "content": "Sera of 656 patients in seven age groups were tested by hemagglutination=inhibition (HI) and complement=fixation (CF) tests for antibodies to BK virus. Both tests revealed that BK virus antibodies are common in the population of southern Germany, and that primary infection is apparently acquired during childhood. The highest rate of positive sera, 71% in the HI test and 56% in the CF test, was found in the 15-30 year old group. The antibody titers correlated in both serologic tests, but HI tests were more sensitive and reliable than CF tests. An indirect immunofluorescence assay for the detection of BK virus-specific IgM antibodies was also developed. Studying umbilical cord blood sera from 846 healthy donors, BK virus IgM antibodies were detected in 77 sera (9.1%).", "contents": "BK virus: I. Seroepidemiologic studies and serologic response to viral infection. Sera of 656 patients in seven age groups were tested by hemagglutination=inhibition (HI) and complement=fixation (CF) tests for antibodies to BK virus. Both tests revealed that BK virus antibodies are common in the population of southern Germany, and that primary infection is apparently acquired during childhood. The highest rate of positive sera, 71% in the HI test and 56% in the CF test, was found in the 15-30 year old group. The antibody titers correlated in both serologic tests, but HI tests were more sensitive and reliable than CF tests. An indirect immunofluorescence assay for the detection of BK virus-specific IgM antibodies was also developed. Studying umbilical cord blood sera from 846 healthy donors, BK virus IgM antibodies were detected in 77 sera (9.1%)."}
{"id": "PMID:209297", "title": "BK virus: II. Serologic studies in children with congenital disease and patients with malignant tumors and immunodeficiencies.", "content": "Sera of 451 children with congenital diseases and 185 tumor patients were tested for BK virus-specific antibodies by hemagglutination inhibition and IgM-immunofluorescence tests. Compared to age-matched control groups, higher percentages and significantly elevated geometric mean titers of HI antibodies were found in all patient groups tested. Of children under six months of age with congenital diseases such as dysplasia, cerebral defects, and hyperbilirubinemia and hepatosplenomegaly, 4.2% (17/402) had BK virus-specific IgM antibodies. No positive sera were found in 68 control sera. Of tumor patients 5--15 years of age, 8.6% (16/185) had IgM antibodies to BK virus. In the control group, 30% (3/99) had them. Serial serum samples from 76 tumor patients treated with cytostatic drugs showed seroconversion in three cases. No relationship between certain clinical features and BK virus infection was noted. Isolation of BK virus was successful from urines of two infants with connatal defects, six patients suffering from malignant tumors, and four patients with inherited immunodeficiencies.", "contents": "BK virus: II. Serologic studies in children with congenital disease and patients with malignant tumors and immunodeficiencies. Sera of 451 children with congenital diseases and 185 tumor patients were tested for BK virus-specific antibodies by hemagglutination inhibition and IgM-immunofluorescence tests. Compared to age-matched control groups, higher percentages and significantly elevated geometric mean titers of HI antibodies were found in all patient groups tested. Of children under six months of age with congenital diseases such as dysplasia, cerebral defects, and hyperbilirubinemia and hepatosplenomegaly, 4.2% (17/402) had BK virus-specific IgM antibodies. No positive sera were found in 68 control sera. Of tumor patients 5--15 years of age, 8.6% (16/185) had IgM antibodies to BK virus. In the control group, 30% (3/99) had them. Serial serum samples from 76 tumor patients treated with cytostatic drugs showed seroconversion in three cases. No relationship between certain clinical features and BK virus infection was noted. Isolation of BK virus was successful from urines of two infants with connatal defects, six patients suffering from malignant tumors, and four patients with inherited immunodeficiencies."}
{"id": "PMID:209298", "title": "Localization of papillomavirus and virus-specific antigens in the skin of tumor-bearing Mastomys natalensis (GRA Giessen).", "content": "In skin neoplasms (so-called keratoakanthomas, papillomas, and squamous cell carcinomas) of Mastomys natalensis (GRA Giessen) virus particles and viral antigens were demonstrated in distinct epithelial layers. Nuclei of the upper parts of the stratum granulosum and disintegrated cell parts of the stratum corneum contain viral structures. The localization of virus particles and viral antigens in any skin neoplasms of M. natalensis (GRA Giessen) corresponded to the sites where papillomavirus-specific material had been demonstrated in papillomas of other species.", "contents": "Localization of papillomavirus and virus-specific antigens in the skin of tumor-bearing Mastomys natalensis (GRA Giessen). In skin neoplasms (so-called keratoakanthomas, papillomas, and squamous cell carcinomas) of Mastomys natalensis (GRA Giessen) virus particles and viral antigens were demonstrated in distinct epithelial layers. Nuclei of the upper parts of the stratum granulosum and disintegrated cell parts of the stratum corneum contain viral structures. The localization of virus particles and viral antigens in any skin neoplasms of M. natalensis (GRA Giessen) corresponded to the sites where papillomavirus-specific material had been demonstrated in papillomas of other species."}
{"id": "PMID:209305", "title": "Physiological consequences of mitochondrial antibiotic-resistant mutations in Paramecium: growth-rates, cytochromic defects and cyanide-insensitive respiration of mutant and erythromycin-treated wild-type strains.", "content": "A set of mitochondrial antibiotic-resistant mutants of Paramecium have been analyzed with respect to their growth-rates, cytochromic content and respiratory properties. The mutants could be arranged in a continuous series ranging from strains equivalent to wild-type to severely affected ones; affected strains display longer generation times, reduced amount of cytochrome oxidase and very high levels of cyanideinsensitive respiration. Perfect phenocopies of the mutants were obtained by treating wild-type cells with low concentrations of erythromycin suggesting that the mutations exert their pleiotropic effect by perturbating mitochondria protein synthesis in agreement with the idea that these mutations affect the mitochondrial ribosomes. In the mitochondria of some of the mutants, electrons can be channelled with equal efficiency into the \"classical\" cyanide-sensitive pathway and the alternate cyanide insensitive (and SHAM-sensitive) one, providing direct demonstration of the branching of these two respiratory pathways. In the absence of any added inhibitor, however, electrons tend to be channelled in the cyanide-sensitive pathway. All the physiological data fit perfectly the genetic data concerning the \"stability\" of the various mutations in \"mixed mitochondrial populations\", i.e., markers that were known to be strongly counter-selected with respect to wild-type in such populations correspond to severely affected strains, while markers that were known to be \"stable\" correspond to \"healthy\" strains. A more quantitative analysis of the data shows that that there is little or no \"complementation\" between wild-type and mutated mitochondria in mixed cells indicating a high extent of functional autonomy of mitochondria in Paramecium.", "contents": "Physiological consequences of mitochondrial antibiotic-resistant mutations in Paramecium: growth-rates, cytochromic defects and cyanide-insensitive respiration of mutant and erythromycin-treated wild-type strains. A set of mitochondrial antibiotic-resistant mutants of Paramecium have been analyzed with respect to their growth-rates, cytochromic content and respiratory properties. The mutants could be arranged in a continuous series ranging from strains equivalent to wild-type to severely affected ones; affected strains display longer generation times, reduced amount of cytochrome oxidase and very high levels of cyanideinsensitive respiration. Perfect phenocopies of the mutants were obtained by treating wild-type cells with low concentrations of erythromycin suggesting that the mutations exert their pleiotropic effect by perturbating mitochondria protein synthesis in agreement with the idea that these mutations affect the mitochondrial ribosomes. In the mitochondria of some of the mutants, electrons can be channelled with equal efficiency into the \"classical\" cyanide-sensitive pathway and the alternate cyanide insensitive (and SHAM-sensitive) one, providing direct demonstration of the branching of these two respiratory pathways. In the absence of any added inhibitor, however, electrons tend to be channelled in the cyanide-sensitive pathway. All the physiological data fit perfectly the genetic data concerning the \"stability\" of the various mutations in \"mixed mitochondrial populations\", i.e., markers that were known to be strongly counter-selected with respect to wild-type in such populations correspond to severely affected strains, while markers that were known to be \"stable\" correspond to \"healthy\" strains. A more quantitative analysis of the data shows that that there is little or no \"complementation\" between wild-type and mutated mitochondria in mixed cells indicating a high extent of functional autonomy of mitochondria in Paramecium."}
{"id": "PMID:209306", "title": "Viomycin favours the formation of 70S ribosome couples.", "content": "The peptide antibiotic viomycin at a concentration of 10 muM inhibits E. coli ribosomes to the extent of about 70% as measured in the poly (U) system, and to about 85% in a natural mRNA (R17) system. Ribosomes from M. smegmatis show no activity at all at this concentration of the antibiotic. Experiments on the Mg+2 dependent dissociation and association of the ribosomal subunits revealed that viomycin stabilizes the 70S couples and promotes association of ribosomal subunits. This response is related to the drug action as indicated by the observation that viomycin resistant strains are not affected by viomycin with respect to dissociation and 70S couple information. A model for the inhibitory action of the drug is proposed.", "contents": "Viomycin favours the formation of 70S ribosome couples. The peptide antibiotic viomycin at a concentration of 10 muM inhibits E. coli ribosomes to the extent of about 70% as measured in the poly (U) system, and to about 85% in a natural mRNA (R17) system. Ribosomes from M. smegmatis show no activity at all at this concentration of the antibiotic. Experiments on the Mg+2 dependent dissociation and association of the ribosomal subunits revealed that viomycin stabilizes the 70S couples and promotes association of ribosomal subunits. This response is related to the drug action as indicated by the observation that viomycin resistant strains are not affected by viomycin with respect to dissociation and 70S couple information. A model for the inhibitory action of the drug is proposed."}
{"id": "PMID:209307", "title": "A possible model for the structure of the Neurospora carbamoyl phosphate synthase-aspartate carbamoyl transferase complex enzyme.", "content": "The pyrimidine-3 locus of Neurospora crassa specifies a multienzyme complex comprising pyrimidine-specific carbamoyl phosphate synthase (CPSpyr) and aspartate carbamoyl transferase (ACT). It appears to be divided into a translationally proximal CPS-specific region and a distal ACT-specific region. Levels of complementation for ACT activity between pairs of four pyr-3 CPS+ ACT- mutants showed a range from 12% to 68% of the wild-type level of the enzyme. This is interpreted as interallelic complementation, contradicting certain earlier suggestion of two dissimilar ACT subunits. Proteolysis of an extract from a heterokaryon formed from two of the above CPS+ ACT- alleles (alpha and beta) did not lead to loss of ACT activity, but led to the formation of a fragment with ACT activity with a similar molecular weight (92,000 daltons) to that produced in extracts of wild type strain. The pyr-3 polar mutant 43-174 which is enzymatically CPS+ ACT- and which fails to complement with any other CPS+ ACT- alleles, thus suggesting its location towards the proximal end of the ACT region, has CPS activity associated with a form of 180,000 daltons molecular weight. These findings are used to contruct a model for structure of the native enzyme complex.", "contents": "A possible model for the structure of the Neurospora carbamoyl phosphate synthase-aspartate carbamoyl transferase complex enzyme. The pyrimidine-3 locus of Neurospora crassa specifies a multienzyme complex comprising pyrimidine-specific carbamoyl phosphate synthase (CPSpyr) and aspartate carbamoyl transferase (ACT). It appears to be divided into a translationally proximal CPS-specific region and a distal ACT-specific region. Levels of complementation for ACT activity between pairs of four pyr-3 CPS+ ACT- mutants showed a range from 12% to 68% of the wild-type level of the enzyme. This is interpreted as interallelic complementation, contradicting certain earlier suggestion of two dissimilar ACT subunits. Proteolysis of an extract from a heterokaryon formed from two of the above CPS+ ACT- alleles (alpha and beta) did not lead to loss of ACT activity, but led to the formation of a fragment with ACT activity with a similar molecular weight (92,000 daltons) to that produced in extracts of wild type strain. The pyr-3 polar mutant 43-174 which is enzymatically CPS+ ACT- and which fails to complement with any other CPS+ ACT- alleles, thus suggesting its location towards the proximal end of the ACT region, has CPS activity associated with a form of 180,000 daltons molecular weight. These findings are used to contruct a model for structure of the native enzyme complex."}
{"id": "PMID:209308", "title": "Selection and characterization of nuclear mutations affecting mitochondria in Paramecium.", "content": "A screening method, based upon resistance to a tetrazolium salt (TTC), is described which permitted the isolation in Paramecium of 28 mutants resistant to TTC. These mutants displayed various defects in mitochondrial functions (cytochromic content cyanide insensitive respiration). Some mutations seemed to affect directly the respiration chain while others seemed to cause indirect modifications, possibly altering mitochondrial protein synthesis. Genetic analysis of four mutants showed in all that the resistance to TTC was of nuclear origin.", "contents": "Selection and characterization of nuclear mutations affecting mitochondria in Paramecium. A screening method, based upon resistance to a tetrazolium salt (TTC), is described which permitted the isolation in Paramecium of 28 mutants resistant to TTC. These mutants displayed various defects in mitochondrial functions (cytochromic content cyanide insensitive respiration). Some mutations seemed to affect directly the respiration chain while others seemed to cause indirect modifications, possibly altering mitochondrial protein synthesis. Genetic analysis of four mutants showed in all that the resistance to TTC was of nuclear origin."}
{"id": "PMID:209309", "title": "Catabolite repression in Escherichia coli mutants lacking cyclic AMP.", "content": "The regulation of catabolite repression of beta-galactosidase has been studied in Escherichia coli mutants deleted for the adenyl cyclase gene (cya delta), and thus unable to synthesize cyclic AMP. It has been found that, provided a second mutation occurs either in the crp gene coding for the catabolite gene activator protein (CAP) or in the Lactose region, these mutants exhibit catabolite repression. If the catabolite repression seen in the mutant strains corresponds to the mechanism operating in wild-type cells the results would suggest that the intracellular concentration of cyclic AMP cannot be the unique regulator of catabolite repression.", "contents": "Catabolite repression in Escherichia coli mutants lacking cyclic AMP. The regulation of catabolite repression of beta-galactosidase has been studied in Escherichia coli mutants deleted for the adenyl cyclase gene (cya delta), and thus unable to synthesize cyclic AMP. It has been found that, provided a second mutation occurs either in the crp gene coding for the catabolite gene activator protein (CAP) or in the Lactose region, these mutants exhibit catabolite repression. If the catabolite repression seen in the mutant strains corresponds to the mechanism operating in wild-type cells the results would suggest that the intracellular concentration of cyclic AMP cannot be the unique regulator of catabolite repression."}
{"id": "PMID:209310", "title": "Catabolite modulator factor: physiological properties and in vivo effects.", "content": "Catabolite modulator factor (CMF) specifically inhibits the expression of operons sensitive to catabolite repression. Systems known to be catabolite independent are not affected by CMF. The rate of metabolism of CMF depends on the extent of catabolite repression: it is slow under conditions of strong repression and high in catabolically derepressed cells. Cyclic AMP does not interfere with the rate of CMF metabolism. It has been found that a certain class of crp mutants are partially resistant to the repressive effect of CMF. Our results provide considerable support for the existence of an additional negative control in the regulation of catabolite repression.", "contents": "Catabolite modulator factor: physiological properties and in vivo effects. Catabolite modulator factor (CMF) specifically inhibits the expression of operons sensitive to catabolite repression. Systems known to be catabolite independent are not affected by CMF. The rate of metabolism of CMF depends on the extent of catabolite repression: it is slow under conditions of strong repression and high in catabolically derepressed cells. Cyclic AMP does not interfere with the rate of CMF metabolism. It has been found that a certain class of crp mutants are partially resistant to the repressive effect of CMF. Our results provide considerable support for the existence of an additional negative control in the regulation of catabolite repression."}
{"id": "PMID:209311", "title": "Localization of glycosyl transferases in plasma membranes from Dictyostelium discoideum.", "content": "Crude membranes from vegetative and aggregation competent cells of Dictyostelium discoideum Ax 2 were separated by a combination of differential and sucrose gradient centrifugation. A fraction mainly containing plasma membranes could be isolated. The high degree of purity was demonstrated by electron microscopy and by the presence of marker enzymes typical for the plasma membrane and the absence of enzymes characteristic for other subcellular compartments. Furthermore surface labelling with radioactive 1--fluoro--2,4--dinitrobenzene--14C and cAMP binding capacity were introduced as plasma membrane markers. In the pure plasma membrane fraction endogenous activities of D--mannosyl-, D--glucosyl- and N--Acetyl--D--glucosaminyl--transferases were present. The activities in plasma membranes of aggregation competent cells were up to thirty times higher than in membranes isolated from vegetative cells.", "contents": "Localization of glycosyl transferases in plasma membranes from Dictyostelium discoideum. Crude membranes from vegetative and aggregation competent cells of Dictyostelium discoideum Ax 2 were separated by a combination of differential and sucrose gradient centrifugation. A fraction mainly containing plasma membranes could be isolated. The high degree of purity was demonstrated by electron microscopy and by the presence of marker enzymes typical for the plasma membrane and the absence of enzymes characteristic for other subcellular compartments. Furthermore surface labelling with radioactive 1--fluoro--2,4--dinitrobenzene--14C and cAMP binding capacity were introduced as plasma membrane markers. In the pure plasma membrane fraction endogenous activities of D--mannosyl-, D--glucosyl- and N--Acetyl--D--glucosaminyl--transferases were present. The activities in plasma membranes of aggregation competent cells were up to thirty times higher than in membranes isolated from vegetative cells."}
{"id": "PMID:209312", "title": "Cyclic AMP increase the Na+ permeability of the avian erythrocyte membrane by a process which does not involve protein phosphorylation.", "content": "Preparations of avian erythrocyte plasma membranes have been made which are in the form of sealed vesicles. Using these preparations the permeability of the membranes to N+, K+, Mg2+ and Ca2+ was measured. Monobutyryl cyclic AMP and cyclic AMP increased the permeability to Na+ and Ca+ under conditions where no protein phosphorylation could occur. The only effect of phosphorylation of membrane proteins was to reduce Ca+ permeability. It is thus concluded that cyclic AMP increases Na+ permeability in the avian erythroycte by a direct effect which does not involve protein phosphorylation.", "contents": "Cyclic AMP increase the Na+ permeability of the avian erythrocyte membrane by a process which does not involve protein phosphorylation. Preparations of avian erythrocyte plasma membranes have been made which are in the form of sealed vesicles. Using these preparations the permeability of the membranes to N+, K+, Mg2+ and Ca2+ was measured. Monobutyryl cyclic AMP and cyclic AMP increased the permeability to Na+ and Ca+ under conditions where no protein phosphorylation could occur. The only effect of phosphorylation of membrane proteins was to reduce Ca+ permeability. It is thus concluded that cyclic AMP increases Na+ permeability in the avian erythroycte by a direct effect which does not involve protein phosphorylation."}
{"id": "PMID:209313", "title": "Decrease of collagen biosynthesis ability of rat kidney fibroblasts transformed with SV--40 virus.", "content": "Rat kidney fibroblasts transformed with SV-40 produce \"in vitro\" a significantly lower amount of hydroxyproline-containing material which is collagenase sensitive as compared to normal cells. In contrast to normal fibroblast cultures, no collagenous material was found by histochemical methods in intercellular spaces of transformed cultures.", "contents": "Decrease of collagen biosynthesis ability of rat kidney fibroblasts transformed with SV--40 virus. Rat kidney fibroblasts transformed with SV-40 produce \"in vitro\" a significantly lower amount of hydroxyproline-containing material which is collagenase sensitive as compared to normal cells. In contrast to normal fibroblast cultures, no collagenous material was found by histochemical methods in intercellular spaces of transformed cultures."}
{"id": "PMID:209314", "title": "The effect of cyclic nucleotides and protein phosphorylation on the permeability of human erythrocyte ghosts to certain cations.", "content": "Preparations of human erythrocyte membranes have been made which are in the form of sealed vesicles and which behave as osmometers on suspension in solutions of simple inorganic salts. Using these preparations the permeability of the membranes to Na+, K+, Mg2+ and Ca2+ was measured. Cyclic AMP (but not cyclic GMP) increased the permeability of the membranes to Ca2+ with a half maximal effect at a concentration of 25 microgram but did not affect the permeability to the other ions tested. Phosphorylation of proteins in the erthrocyte membrane lowered the permeability to Ca2+ without affecting the permeability to the other ions tested and there was a good correlation between the time course of protein phosphorylation and decrease in Ca2+ permeability. It is postulated that the system through which cyclic AMP causes an initial rapid rise in Ca2+ permeability followed by increased phosphorylation of membrane proteins and reduced Ca2+ permeability may have a widespread occurrence in biological systems and serve to control the concentration of Ca2+ in the cytoplasm.", "contents": "The effect of cyclic nucleotides and protein phosphorylation on the permeability of human erythrocyte ghosts to certain cations. Preparations of human erythrocyte membranes have been made which are in the form of sealed vesicles and which behave as osmometers on suspension in solutions of simple inorganic salts. Using these preparations the permeability of the membranes to Na+, K+, Mg2+ and Ca2+ was measured. Cyclic AMP (but not cyclic GMP) increased the permeability of the membranes to Ca2+ with a half maximal effect at a concentration of 25 microgram but did not affect the permeability to the other ions tested. Phosphorylation of proteins in the erthrocyte membrane lowered the permeability to Ca2+ without affecting the permeability to the other ions tested and there was a good correlation between the time course of protein phosphorylation and decrease in Ca2+ permeability. It is postulated that the system through which cyclic AMP causes an initial rapid rise in Ca2+ permeability followed by increased phosphorylation of membrane proteins and reduced Ca2+ permeability may have a widespread occurrence in biological systems and serve to control the concentration of Ca2+ in the cytoplasm."}
{"id": "PMID:209319", "title": "EMS-induced reversion studies in the white locus of Drosophila melanogaster.", "content": "5 white-locus mutants of Drosophila melanogaster, respresenting 5 different sub-sites, were treated with EMS and tested for reversion to wild-type. 4 of them were genuine mutants and one was not. Moreover, the ability of the 4 mutants to revert to wild-type differed from one another which therefore reflects a qualitatively distinct alteration in the genetic material delimited by each mutant.", "contents": "EMS-induced reversion studies in the white locus of Drosophila melanogaster. 5 white-locus mutants of Drosophila melanogaster, respresenting 5 different sub-sites, were treated with EMS and tested for reversion to wild-type. 4 of them were genuine mutants and one was not. Moreover, the ability of the 4 mutants to revert to wild-type differed from one another which therefore reflects a qualitatively distinct alteration in the genetic material delimited by each mutant."}
{"id": "PMID:209322", "title": "Inhibition of postreplication repair and the enhancement of induction of SV40 virus from transformed hamster kidney cells.", "content": "The induction by ultraviolet light of simian virus 40 (SV40) from two SV40--transformed hamster kidney cell lines is enhanced by caffeine. In order to investigate the mechanism responsible for this enhancement, the effect of caffeine on postreplication repair of DNA damaged by UV light was studied utilizing alkaline sucrose-gradient sedimentation. Caffeine at concentrations of 0.5, 1.0 or 2.0 mM inhibited the filling of gaps during postreplication repair. In addition, caffeine was found to potentiate cell killing by mitomycin C, an alkylating agent, and to enhance SV40 induction by mitomycin C. We postulate that the persistence of gaps in DNA, caused by the presence of caffeine, results in the enhancement of SV40 virus induction.", "contents": "Inhibition of postreplication repair and the enhancement of induction of SV40 virus from transformed hamster kidney cells. The induction by ultraviolet light of simian virus 40 (SV40) from two SV40--transformed hamster kidney cell lines is enhanced by caffeine. In order to investigate the mechanism responsible for this enhancement, the effect of caffeine on postreplication repair of DNA damaged by UV light was studied utilizing alkaline sucrose-gradient sedimentation. Caffeine at concentrations of 0.5, 1.0 or 2.0 mM inhibited the filling of gaps during postreplication repair. In addition, caffeine was found to potentiate cell killing by mitomycin C, an alkylating agent, and to enhance SV40 induction by mitomycin C. We postulate that the persistence of gaps in DNA, caused by the presence of caffeine, results in the enhancement of SV40 virus induction."}
{"id": "PMID:209323", "title": "Embryopathies due to spermatozoal impairment in Xenopus laevis.", "content": "An in vitro test system, involving gametes of Xenopus laevis has been used to study the effect of antifertility agents upon spermatozoa as manifest in developing embryos. Exposure to either the isomeric forms of dimethylmyleran, methyl methanesulphonate or gamma-radiation led to development of a range of embryopathies, whereas treatment with steroidal drugs or the rodent epididymal chemosterilants alpha-chlorohydrin and trimethylphosphate was compatible with production of apparently normal offspring.", "contents": "Embryopathies due to spermatozoal impairment in Xenopus laevis. An in vitro test system, involving gametes of Xenopus laevis has been used to study the effect of antifertility agents upon spermatozoa as manifest in developing embryos. Exposure to either the isomeric forms of dimethylmyleran, methyl methanesulphonate or gamma-radiation led to development of a range of embryopathies, whereas treatment with steroidal drugs or the rodent epididymal chemosterilants alpha-chlorohydrin and trimethylphosphate was compatible with production of apparently normal offspring."}
{"id": "PMID:209324", "title": "Mutagenicity of dimethylnitrosamine and ethyl methanesulfonate as determined by the host-mediated CHO/HGPRT assay.", "content": "Host-mediated assays have been developed to allow determination of the mutagenic potential of promutagens and procarcinogens which require metabolic activation to exert their effects on indicator organisms. We report here the development of the host-(mouse)-mediated CHO/HGPRT system using the procarcinogen dimethylnitrosamine (DMN) as a model agent. Using a 2--h treatment time, we observed a linear dose-response relationship up to 250 mg of DMN per kg body weight. At 100 and 500 mg/kg DMN, mutation induction increased with time up to at least 6 h. DMN was not mutagenic when tested in vitro. Athymic (nude) mice, their phenotypically normal littermates, or BALB/c mice of both sexes were found to be suitable as hosts. A time- and dose-dependency of induced mutation frequency by a direct-acting agent, ethyl methanesulfonate (EMS), was observed in both the in vitro and the host-mediated assays.", "contents": "Mutagenicity of dimethylnitrosamine and ethyl methanesulfonate as determined by the host-mediated CHO/HGPRT assay. Host-mediated assays have been developed to allow determination of the mutagenic potential of promutagens and procarcinogens which require metabolic activation to exert their effects on indicator organisms. We report here the development of the host-(mouse)-mediated CHO/HGPRT system using the procarcinogen dimethylnitrosamine (DMN) as a model agent. Using a 2--h treatment time, we observed a linear dose-response relationship up to 250 mg of DMN per kg body weight. At 100 and 500 mg/kg DMN, mutation induction increased with time up to at least 6 h. DMN was not mutagenic when tested in vitro. Athymic (nude) mice, their phenotypically normal littermates, or BALB/c mice of both sexes were found to be suitable as hosts. A time- and dose-dependency of induced mutation frequency by a direct-acting agent, ethyl methanesulfonate (EMS), was observed in both the in vitro and the host-mediated assays."}
{"id": "PMID:209325", "title": "Dose-rate effects of ethyl methanesulfonate on survival and mutation induction in cultured Chinese hamster cells.", "content": "The dose-rate effects of ethyl methanesulfonate (EMS) on the survival and induction of mutations in Chinese hamster Don cells were investigated. The most effective time of exposure to EMS for reducing the surviving fraction of cells was 4 h, shorter and longer exposure times being less effective. The threshold or minimal concentration of EMS giving a surviving fraction of 0.5 was 0.05 mg/ml. The minimal effective time of exposure to EMS for cell death was 1 h. Corrected survival curves showed that longer exposure times at lower dose rates of EMS had less cytotoxic effect than shorter exposure times at higher dose rates. After exposure of Don cells to various doses of EMS for various times, the frequencies of mutations resistant to 6--thioguanine (6TG) were measured. An exposure time of 4 h produced a lower mutation frequency than shorter or longer exposure times that resulted in the same surviving fraction of cells. An exposure time of 20 h produced the highest induced mutation frequency. This system using cultured Chinese hamster cells should be useful as a sensitive procedure for detecting the mutagenic actions of chemicals.", "contents": "Dose-rate effects of ethyl methanesulfonate on survival and mutation induction in cultured Chinese hamster cells. The dose-rate effects of ethyl methanesulfonate (EMS) on the survival and induction of mutations in Chinese hamster Don cells were investigated. The most effective time of exposure to EMS for reducing the surviving fraction of cells was 4 h, shorter and longer exposure times being less effective. The threshold or minimal concentration of EMS giving a surviving fraction of 0.5 was 0.05 mg/ml. The minimal effective time of exposure to EMS for cell death was 1 h. Corrected survival curves showed that longer exposure times at lower dose rates of EMS had less cytotoxic effect than shorter exposure times at higher dose rates. After exposure of Don cells to various doses of EMS for various times, the frequencies of mutations resistant to 6--thioguanine (6TG) were measured. An exposure time of 4 h produced a lower mutation frequency than shorter or longer exposure times that resulted in the same surviving fraction of cells. An exposure time of 20 h produced the highest induced mutation frequency. This system using cultured Chinese hamster cells should be useful as a sensitive procedure for detecting the mutagenic actions of chemicals."}
{"id": "PMID:209327", "title": "Effect of sodium selenite and methyl methanesulfonate or N-hydroxy-2-acetylaminofluorene co-exposure on sister-chromatid exchange production in human whole blood cultures.", "content": "Sodium selenite (Na2SeO3) was tested for its sister-chromatid exchange (SCE)-inducing ability in human whole blood cultures and for the effect of its co-exposure with methyl methanesulfonate (MMS)  or N-hydroxy-2-acetylaminofluorene (N-OH-AAF) on SCE frequency. Long exposure times (77 h and 96 h) to 3.95 X 10(-6) M Na2SeO3 resulted in cell death as measured by mitotic indices, but mitotic figures were present after exposure to higher concentrations for a shorter time (19 h). High Na2SeO3 concentrations (7.90 X 10(-6) and 1.19 X 10(-5) M) resulted in a three-fold increase in the SCE frequency above background level (6--7 SCEs/cell). Exposure of lymphocytes to 1 X 10(-4) M MMS for the last 19 h of culture yielded an average SCE frequency of 30.17 +/- 0.75 while a similar exposure to 2.7 X 10(-5) M N-OH-AAF resulted in 13.61 +/- 0.43 SCEs/cell. Simultaneous addition of the high Na2SeO3 concentrations and MMS or N-OH-AAF to the cultures resulted in SCE frequencies that were 25--30% and 11--17%, respectively, below the sum of the SCE frequencies produced by the individual compounds.", "contents": "Effect of sodium selenite and methyl methanesulfonate or N-hydroxy-2-acetylaminofluorene co-exposure on sister-chromatid exchange production in human whole blood cultures. Sodium selenite (Na2SeO3) was tested for its sister-chromatid exchange (SCE)-inducing ability in human whole blood cultures and for the effect of its co-exposure with methyl methanesulfonate (MMS)  or N-hydroxy-2-acetylaminofluorene (N-OH-AAF) on SCE frequency. Long exposure times (77 h and 96 h) to 3.95 X 10(-6) M Na2SeO3 resulted in cell death as measured by mitotic indices, but mitotic figures were present after exposure to higher concentrations for a shorter time (19 h). High Na2SeO3 concentrations (7.90 X 10(-6) and 1.19 X 10(-5) M) resulted in a three-fold increase in the SCE frequency above background level (6--7 SCEs/cell). Exposure of lymphocytes to 1 X 10(-4) M MMS for the last 19 h of culture yielded an average SCE frequency of 30.17 +/- 0.75 while a similar exposure to 2.7 X 10(-5) M N-OH-AAF resulted in 13.61 +/- 0.43 SCEs/cell. Simultaneous addition of the high Na2SeO3 concentrations and MMS or N-OH-AAF to the cultures resulted in SCE frequencies that were 25--30% and 11--17%, respectively, below the sum of the SCE frequencies produced by the individual compounds."}
{"id": "PMID:209337", "title": "Cellular transformation and the 'morphologic phenotype' of transformed cells.", "content": "Expression of the product of the transforming gene (src) of RNA tumour viruses promotes growth and usually alters the adhesion, appearance and surface properties of cultured fibroblasts. The latter group of properties termed the 'morphologic phenotype' of transformed cells is largely due to diminished cell-to-substratum adhesion. The role of cyclic AMP, cell surface protein (CSP), and other factors in producing the 'morphologic phenotype' are discussed. The effects of src expression bear a striking resemblance to the action of peptide hormones such as insulin on appropriate target cells.", "contents": "Cellular transformation and the 'morphologic phenotype' of transformed cells. Expression of the product of the transforming gene (src) of RNA tumour viruses promotes growth and usually alters the adhesion, appearance and surface properties of cultured fibroblasts. The latter group of properties termed the 'morphologic phenotype' of transformed cells is largely due to diminished cell-to-substratum adhesion. The role of cyclic AMP, cell surface protein (CSP), and other factors in producing the 'morphologic phenotype' are discussed. The effects of src expression bear a striking resemblance to the action of peptide hormones such as insulin on appropriate target cells."}
{"id": "PMID:209345", "title": "Binding of (3H)dihydroalprenolol to beta adrenoceptors of cells isolated from adult rat heart.", "content": "Myocardial cells isolated from adult rat heart bind (3H)dihydroalprenolol. Sixty-one percent of this binding appeared to be at the beta adrenoceptors since it was inhibited by saturating quantities of the beta antagonist propranolol or by the beta agonist isoprenaline. The binding is stereoselective as the l-isomer of isoprenaline caused greater inhibition than the d-isomer. The binding of (3H)dihydroalprenolol to beta adrenoceptors was saturable; half maximum binding occurred at about 8 nM and full saturation at 30--40nM.", "contents": "Binding of (3H)dihydroalprenolol to beta adrenoceptors of cells isolated from adult rat heart. Myocardial cells isolated from adult rat heart bind (3H)dihydroalprenolol. Sixty-one percent of this binding appeared to be at the beta adrenoceptors since it was inhibited by saturating quantities of the beta antagonist propranolol or by the beta agonist isoprenaline. The binding is stereoselective as the l-isomer of isoprenaline caused greater inhibition than the d-isomer. The binding of (3H)dihydroalprenolol to beta adrenoceptors was saturable; half maximum binding occurred at about 8 nM and full saturation at 30--40nM."}
{"id": "PMID:209347", "title": "A simple method for sampling murine pulmonary and cardiac tissues for analysis of cyclic nucleotide levels.", "content": "A simple method for the rapid removal and freezing of mouse cardiac and pulmonary tissues is described. Samples thus obtained were judged to be suitable for valid estimation of in vivo levels of cyclic AMP and cyclic GMP based on the following findings: (a) the samples could be obtained and frozen in the very short time period of a few seconds; (b) no indication of adverse effects of the collection procedure was found upon examination of chemical indicators of energy metabolism; (c) the apparent rates of change of cyclic AMP and cyclic GMP levels during the first seconds after tissue isolation could produce small, but acceptable errors; and (d) dose-dependent elevations of pulmonary cAMP levels consistent with known effects in vitro were found after in vivo administration of isoproternol.", "contents": "A simple method for sampling murine pulmonary and cardiac tissues for analysis of cyclic nucleotide levels. A simple method for the rapid removal and freezing of mouse cardiac and pulmonary tissues is described. Samples thus obtained were judged to be suitable for valid estimation of in vivo levels of cyclic AMP and cyclic GMP based on the following findings: (a) the samples could be obtained and frozen in the very short time period of a few seconds; (b) no indication of adverse effects of the collection procedure was found upon examination of chemical indicators of energy metabolism; (c) the apparent rates of change of cyclic AMP and cyclic GMP levels during the first seconds after tissue isolation could produce small, but acceptable errors; and (d) dose-dependent elevations of pulmonary cAMP levels consistent with known effects in vitro were found after in vivo administration of isoproternol."}
{"id": "PMID:209349", "title": "Effects of Mg2+, Mn2+ and Ca2+ on adenylcyclase activity. Evidence for a metallic site.", "content": "In membrane preparations from immature erythrocytes from rats the effects of the divalent cations Mg2+, Mn2+ and Ca2+ on basal activity of adenylcyclase as well as on enzyme activity stimulated by isoprenaline (Ipn) or guanylyl-imidodiphosphate [Gpp(NH)p] were investigated.--Mn2+ is a ten-fold stronger activator of the enzyme than Mg2+ irrespective of the stimulant used. At suboptimal concentrations of the cations at all concentrations of Gpp(NH)p used (10(-6) to 10(-3) M) reaction velocities increase progressively over an incubation period of 40 min. Optimal cation concentrations, however, i.e. 3 x 10(-3) M Mn2+ and 3 x 10(-2)M Mg2+ elicit a constant and at 10(-4) M Gpp(NH)p maximal reaction velocity. In contrast, the Ipn-stimulated  cAMP synthesis proceeds linearly at all Ipn concentrations used; a change of cation concentrations elicits only a change in reaction velocity, which is maximal at 10(-3) M Mn2+ and 10(-2) M Mg2+ respectively.--Ca2+ inhibits adenylcyclase activity in a non-competitive manner, irrespective of the stimulant and ion concentration used. The Mg2+-activated enzyme, however, is more susceptible to the inhibiting effect of Ca2+ than the Mn2+-activated enzyme.--It is concluded that Mn2+ and Mg2+ are allosteric effectors of the enzyme adenylcyclase, acting at a Me2+-site of the catalytic unit of adenylcyclase.", "contents": "Effects of Mg2+, Mn2+ and Ca2+ on adenylcyclase activity. Evidence for a metallic site. In membrane preparations from immature erythrocytes from rats the effects of the divalent cations Mg2+, Mn2+ and Ca2+ on basal activity of adenylcyclase as well as on enzyme activity stimulated by isoprenaline (Ipn) or guanylyl-imidodiphosphate [Gpp(NH)p] were investigated.--Mn2+ is a ten-fold stronger activator of the enzyme than Mg2+ irrespective of the stimulant used. At suboptimal concentrations of the cations at all concentrations of Gpp(NH)p used (10(-6) to 10(-3) M) reaction velocities increase progressively over an incubation period of 40 min. Optimal cation concentrations, however, i.e. 3 x 10(-3) M Mn2+ and 3 x 10(-2)M Mg2+ elicit a constant and at 10(-4) M Gpp(NH)p maximal reaction velocity. In contrast, the Ipn-stimulated  cAMP synthesis proceeds linearly at all Ipn concentrations used; a change of cation concentrations elicits only a change in reaction velocity, which is maximal at 10(-3) M Mn2+ and 10(-2) M Mg2+ respectively.--Ca2+ inhibits adenylcyclase activity in a non-competitive manner, irrespective of the stimulant and ion concentration used. The Mg2+-activated enzyme, however, is more susceptible to the inhibiting effect of Ca2+ than the Mn2+-activated enzyme.--It is concluded that Mn2+ and Mg2+ are allosteric effectors of the enzyme adenylcyclase, acting at a Me2+-site of the catalytic unit of adenylcyclase."}
{"id": "PMID:209350", "title": "Further evidence for a change in central alpha-adrenergic receptor sensitivity after withdrawal from long-term haloperidol treatment.", "content": "Phenoxybenzamine, FLA-63 and alpha-MT produced less locomotor depression in mice withdrawn for 4 days from a 21 day treatment with haloperidol than that produced in vehicle-treated animals. There were no differences between the two groups when challenged with yohimbine or phentolamine. The data support the hypothesis that central alpha-adrenergic receptors had become supersensitive and suggest that the sensitivity changes are restricted to post-synaptic receptors.", "contents": "Further evidence for a change in central alpha-adrenergic receptor sensitivity after withdrawal from long-term haloperidol treatment. Phenoxybenzamine, FLA-63 and alpha-MT produced less locomotor depression in mice withdrawn for 4 days from a 21 day treatment with haloperidol than that produced in vehicle-treated animals. There were no differences between the two groups when challenged with yohimbine or phentolamine. The data support the hypothesis that central alpha-adrenergic receptors had become supersensitive and suggest that the sensitivity changes are restricted to post-synaptic receptors."}
{"id": "PMID:209351", "title": "Structural and steric requirements for beta-phenethylamines as agonists of the noradrenergic cyclic AMP generating system in the rat limbic forebrain.", "content": "The present studies were undertaken to assess the structural and steric requirements for beta-phenethylamines as agonists of the noradrenergic cyclic AMP generating system in slices of the rat limbic forebrain. Significant agonist activity of beta-phenethylamines requires a beta-3,4-dihydroxyphenethylamine with a beta-hydroxyl group in the R configuration. Thus, dopamine did not stimulate the system at concentrations up to 10(-3) M. Moreover, beta-hydroxyphenethylamines without a 3,4-catechol group (octopamine, phenylephrine, p-hydroxynorephedrine, metaraminol and methoxamine) - though exerting alpha-agonist activity in peripheral tissues - lack agonist activity in this particular cyclic AMP generating system. The effects of (R)-norepinephrine and (R)-isoproterenol at maximal concentrations were not additive. The results lend further support to the view that the cyclic AMP generating system in slices of the limbic forebrain is part of a norepinephrine receptor coupled adenylate cyclase system with a subpopulation of receptors that are beta in nature.", "contents": "Structural and steric requirements for beta-phenethylamines as agonists of the noradrenergic cyclic AMP generating system in the rat limbic forebrain. The present studies were undertaken to assess the structural and steric requirements for beta-phenethylamines as agonists of the noradrenergic cyclic AMP generating system in slices of the rat limbic forebrain. Significant agonist activity of beta-phenethylamines requires a beta-3,4-dihydroxyphenethylamine with a beta-hydroxyl group in the R configuration. Thus, dopamine did not stimulate the system at concentrations up to 10(-3) M. Moreover, beta-hydroxyphenethylamines without a 3,4-catechol group (octopamine, phenylephrine, p-hydroxynorephedrine, metaraminol and methoxamine) - though exerting alpha-agonist activity in peripheral tissues - lack agonist activity in this particular cyclic AMP generating system. The effects of (R)-norepinephrine and (R)-isoproterenol at maximal concentrations were not additive. The results lend further support to the view that the cyclic AMP generating system in slices of the limbic forebrain is part of a norepinephrine receptor coupled adenylate cyclase system with a subpopulation of receptors that are beta in nature."}
{"id": "PMID:209352", "title": "Differential effects of benzamides and thioxanthenes on dopamine-elicited accumulation of cyclic AMP in isolated rabbit retina.", "content": "Benzamides or thioxanthenes were tested as potential antagonists of the cyclic AMP accumulation induced by 10(-4) M dopamine in intact rabbit retinae in vitro in the presence of 5 to 7 mM theophylline. The neuroleptic sulpiride (10(-4) M) was found to be totally inactive whereas a substituted benzamide (clebopride) had small but significant antagonist effect at the same concentration. Among thioxanthenes, isomers of cisconfiguration, which are potent neuroleptics, completely inhibit the cyclic AMP accumulation induced by dopamine, in contrast to trans-isomers which had no inhibitory effects. These data would confirm that retina in vitro is another suitable model for screening antipsychotic activity of classical neuroleptics and that the mechanism of action of sulpiride still needs further investigation.", "contents": "Differential effects of benzamides and thioxanthenes on dopamine-elicited accumulation of cyclic AMP in isolated rabbit retina. Benzamides or thioxanthenes were tested as potential antagonists of the cyclic AMP accumulation induced by 10(-4) M dopamine in intact rabbit retinae in vitro in the presence of 5 to 7 mM theophylline. The neuroleptic sulpiride (10(-4) M) was found to be totally inactive whereas a substituted benzamide (clebopride) had small but significant antagonist effect at the same concentration. Among thioxanthenes, isomers of cisconfiguration, which are potent neuroleptics, completely inhibit the cyclic AMP accumulation induced by dopamine, in contrast to trans-isomers which had no inhibitory effects. These data would confirm that retina in vitro is another suitable model for screening antipsychotic activity of classical neuroleptics and that the mechanism of action of sulpiride still needs further investigation."}
{"id": "PMID:209353", "title": "Alpha-receptor-mediated modulation of 3H-noradrenaline release from rat brain cortex synaptosomes.", "content": "The effects of oxymetazoline and noradrenaline (in the presence of desipramine) on the release of 3H-noradrenaline from rat brain cortex synaptosomes were studied using a superfusion technique. Both drugs (at 1 micrometer concentrations) were found to reduce the depolarization-induced (15 mM K+) release of 3H-noradrenaline. The release-modulating effect of noradrenaline was antagonized by phentolamine and yohimbine. The data provide direct evidence for the hypothesis that alpha-receptors modulating the release of noradrenaline are localized on varicosities of central noradrenergic neurones.", "contents": "Alpha-receptor-mediated modulation of 3H-noradrenaline release from rat brain cortex synaptosomes. The effects of oxymetazoline and noradrenaline (in the presence of desipramine) on the release of 3H-noradrenaline from rat brain cortex synaptosomes were studied using a superfusion technique. Both drugs (at 1 micrometer concentrations) were found to reduce the depolarization-induced (15 mM K+) release of 3H-noradrenaline. The release-modulating effect of noradrenaline was antagonized by phentolamine and yohimbine. The data provide direct evidence for the hypothesis that alpha-receptors modulating the release of noradrenaline are localized on varicosities of central noradrenergic neurones."}
{"id": "PMID:209357", "title": "[Transformation of long reticulofugal impulse trains by interneurons monosynaptically linked to the reticulospinal tract].", "content": "Transmission of the reticulofugal activity via the interneurons localized in the ventromedial grey matter of the lumbar region and monosynaptically activated from the reticulospinal fibres was studied in anaesthetized immobilized cats. Interneurons usually generated stationary discharges when reticulospinal pathways were rhythmically stimulated with relatively low frequencies (up to 80-100/s); with further increase of stimulation frequency the discharges became non-stationary (initial high-frequency phase was followed by partial or complete discharge suppression). Maximal firing rate at the initial phase could not exceed 180-230 imp./s. The \"transfer function\" (the ratio of response frequency to stimulation frequency) reached 0.7-0.8 at low stimulation frequencies and decreased substantially at higher ones. Using mathematical modelling of the excitatory and post-activation inhibitory actions in these neurons, the parameters have been estimated which determine the transfer properties, of the interneuronal population relaying reticulofugal activity.", "contents": "[Transformation of long reticulofugal impulse trains by interneurons monosynaptically linked to the reticulospinal tract]. Transmission of the reticulofugal activity via the interneurons localized in the ventromedial grey matter of the lumbar region and monosynaptically activated from the reticulospinal fibres was studied in anaesthetized immobilized cats. Interneurons usually generated stationary discharges when reticulospinal pathways were rhythmically stimulated with relatively low frequencies (up to 80-100/s); with further increase of stimulation frequency the discharges became non-stationary (initial high-frequency phase was followed by partial or complete discharge suppression). Maximal firing rate at the initial phase could not exceed 180-230 imp./s. The \"transfer function\" (the ratio of response frequency to stimulation frequency) reached 0.7-0.8 at low stimulation frequencies and decreased substantially at higher ones. Using mathematical modelling of the excitatory and post-activation inhibitory actions in these neurons, the parameters have been estimated which determine the transfer properties, of the interneuronal population relaying reticulofugal activity."}
{"id": "PMID:209358", "title": "[Responses of accessory nerve nucleus motor neurons to stimulation by different sensory inputs].", "content": "Monosynaptic EPSPs in the cat accessory motoneurons were evoked by the stimulation of the cervical dorsal roots (C1 and C2). Responses of these units to the accessory nerve muscle rami stimulation were unstable and polysynaptic. It is supposed that the accessory muscles in the cat (m. sternocleidomastoideus and m. trapezius) receive proprioceptive innervation via the dorsal rami of the upper crevical nerves, and the function of accessory nerve is predominantly motor.", "contents": "[Responses of accessory nerve nucleus motor neurons to stimulation by different sensory inputs]. Monosynaptic EPSPs in the cat accessory motoneurons were evoked by the stimulation of the cervical dorsal roots (C1 and C2). Responses of these units to the accessory nerve muscle rami stimulation were unstable and polysynaptic. It is supposed that the accessory muscles in the cat (m. sternocleidomastoideus and m. trapezius) receive proprioceptive innervation via the dorsal rami of the upper crevical nerves, and the function of accessory nerve is predominantly motor."}
{"id": "PMID:209360", "title": "[Herpetic meningo-encephalitis : emergency E.E.G. diagnosis and neurosurgical treatment (author's transl)].", "content": "Reporting two cases of true herpetic encephalitis, the authors insist on the great diagnostic value of some nearly constant, but transitory, aspects of localised periodic waves in the E.E.G. An emergency cerebral (usually temporal) resection is then advised. Thus focal infection is reduced and intra-cranial hypertension is prevented. Virologic and electron microscopic studies of the cortical specimen establish with certainty the diagnosis of herpetic encephalitis.", "contents": "[Herpetic meningo-encephalitis : emergency E.E.G. diagnosis and neurosurgical treatment (author's transl)]. Reporting two cases of true herpetic encephalitis, the authors insist on the great diagnostic value of some nearly constant, but transitory, aspects of localised periodic waves in the E.E.G. An emergency cerebral (usually temporal) resection is then advised. Thus focal infection is reduced and intra-cranial hypertension is prevented. Virologic and electron microscopic studies of the cortical specimen establish with certainty the diagnosis of herpetic encephalitis."}
{"id": "PMID:209362", "title": "Noradrenergic and dopaminergic regulation of GH and prolactin in baboons.", "content": "Aminergic regulation of growth hormone (GH) and prolactin (Prl) was studied in male adolescent baboons by i.v. infusion of dopamine (DA), norepinephrine (NE), thyrotropin-releasing hormone (TRH), phentolamine, haloperidol, and inhibitors of DA-beta-hydroxylase and peripheral decarboxylase. 20-min infusion of DA (40 microgram/kg.min) and 60-min infusion of NE (0.4 microgram/kg.min) stimulated GH release. The DA-induced GH release was suppressed by concomitant infusion of FLA 63 (inhibitor of NE synthesis from DA) and by phentolamine, indicating alpha-adrenergic mediation of GH release. Microinfection of DA (0.8 microgram/kg) into the medial basal hypothalamus (MBH) lowered basal GH. Prl was released by i.v. TRH, and this effect was suppressed by i.v. DA but not by i.v. NE. Blockade of peripheral decarboxylase by carbidopa elicited a marked and sustained rise in Prl which was inhibited by i.v. DA. Microinjection of NE (0.8 microgram/kg) into the MBH released Prl. These data indicate that in the MBH, alpha-adrenergic mechanisms release GH and Prl, and that dopaminergic mechanisms suppres GH.", "contents": "Noradrenergic and dopaminergic regulation of GH and prolactin in baboons. Aminergic regulation of growth hormone (GH) and prolactin (Prl) was studied in male adolescent baboons by i.v. infusion of dopamine (DA), norepinephrine (NE), thyrotropin-releasing hormone (TRH), phentolamine, haloperidol, and inhibitors of DA-beta-hydroxylase and peripheral decarboxylase. 20-min infusion of DA (40 microgram/kg.min) and 60-min infusion of NE (0.4 microgram/kg.min) stimulated GH release. The DA-induced GH release was suppressed by concomitant infusion of FLA 63 (inhibitor of NE synthesis from DA) and by phentolamine, indicating alpha-adrenergic mediation of GH release. Microinfection of DA (0.8 microgram/kg) into the medial basal hypothalamus (MBH) lowered basal GH. Prl was released by i.v. TRH, and this effect was suppressed by i.v. DA but not by i.v. NE. Blockade of peripheral decarboxylase by carbidopa elicited a marked and sustained rise in Prl which was inhibited by i.v. DA. Microinjection of NE (0.8 microgram/kg) into the MBH released Prl. These data indicate that in the MBH, alpha-adrenergic mechanisms release GH and Prl, and that dopaminergic mechanisms suppres GH."}
{"id": "PMID:209363", "title": "Luteinizing hormone secretion and gonadotropin releasing hormone binding in heifer and steer anterior pituitaries.", "content": "Luteinizing hormone (LH) release and tissue content were studied in explanted bovine pituitaries from heifer and steer during superfusion in vitro. Compared to steer, heifer pituitaries contained significantly more LH and released more LH into the incubation medium. Quantitative response in LH release to gonadotropin releasing hormone (GnRH) stimulation was about equal in heifer and steer, but relative increase was more pronounced in steer. Specific 125I-GnRH binding to dispersed anterior pituitary (AP) cells and isolated plasma membranes was also analyzed. Concentration dependent binding curve of 125I-GnRH to dispersed cells exhibited sigmoid characteristics suggesting positive cooperativity. There was a sex dependent difference, the binding curve for heifer being shifted to the left and reaching saturation at lower GnRH concentrations than that for steer. \"Multisigmoid\" concentration dependent GnRH binding curves were obtained using isolated plasma membranes, revealing the presence of multiple binding sites. One of the binding sites, present in heifer, was absent in the steer derived materials, but could be induced by pretreatment of the steer plasma membranes with 17-beta estradiol as low as 50 pg/ml. It is concluded that the differences in GnRH binding may be responsible, at least in part, for the observed differences in LH secretion pattern between heifer and steer.", "contents": "Luteinizing hormone secretion and gonadotropin releasing hormone binding in heifer and steer anterior pituitaries. Luteinizing hormone (LH) release and tissue content were studied in explanted bovine pituitaries from heifer and steer during superfusion in vitro. Compared to steer, heifer pituitaries contained significantly more LH and released more LH into the incubation medium. Quantitative response in LH release to gonadotropin releasing hormone (GnRH) stimulation was about equal in heifer and steer, but relative increase was more pronounced in steer. Specific 125I-GnRH binding to dispersed anterior pituitary (AP) cells and isolated plasma membranes was also analyzed. Concentration dependent binding curve of 125I-GnRH to dispersed cells exhibited sigmoid characteristics suggesting positive cooperativity. There was a sex dependent difference, the binding curve for heifer being shifted to the left and reaching saturation at lower GnRH concentrations than that for steer. \"Multisigmoid\" concentration dependent GnRH binding curves were obtained using isolated plasma membranes, revealing the presence of multiple binding sites. One of the binding sites, present in heifer, was absent in the steer derived materials, but could be induced by pretreatment of the steer plasma membranes with 17-beta estradiol as low as 50 pg/ml. It is concluded that the differences in GnRH binding may be responsible, at least in part, for the observed differences in LH secretion pattern between heifer and steer."}
{"id": "PMID:209361", "title": "[Unusual clinical course in a case of carcinomatosis of cerebrospinal meninges].", "content": "The authors report the clinical course of a case of carcinomatosis of the cerebrospinal meninges with frequent sudden rises of intracranial pressure and with lethal outcome. The primary tumour was a mucinous carcinoma of the ovary. In treatment Pudenz valve was used successfully for connecting the subarachnoid space of the spinal cord with the peritoneal cavity. This shunting of the cerebrospinal fluid caused no dissemination of the neoplasm within the peritoneal cavity.", "contents": "[Unusual clinical course in a case of carcinomatosis of cerebrospinal meninges]. The authors report the clinical course of a case of carcinomatosis of the cerebrospinal meninges with frequent sudden rises of intracranial pressure and with lethal outcome. The primary tumour was a mucinous carcinoma of the ovary. In treatment Pudenz valve was used successfully for connecting the subarachnoid space of the spinal cord with the peritoneal cavity. This shunting of the cerebrospinal fluid caused no dissemination of the neoplasm within the peritoneal cavity."}
{"id": "PMID:209367", "title": "Multiple mononeuropathy in lymphomatoid granulomatosis: similarity to leprosy.", "content": "Multiple mononeuropathy and anesthetic granulomatous skin lesions were the first manifestations of lymphomatoid granulomatosis in a young woman. The skin lesions resembled those of leprosy. Lymphomatoid granulomatosis is related to midline granulomas and other idiopathic granulomatous angiitic lesions.", "contents": "Multiple mononeuropathy in lymphomatoid granulomatosis: similarity to leprosy. Multiple mononeuropathy and anesthetic granulomatous skin lesions were the first manifestations of lymphomatoid granulomatosis in a young woman. The skin lesions resembled those of leprosy. Lymphomatoid granulomatosis is related to midline granulomas and other idiopathic granulomatous angiitic lesions."}
{"id": "PMID:209369", "title": "[Specific cytoplasmic receptors for steroid homones in benign and malignant breast diseases, in normal glandular tissue and pectoral muscle].", "content": "An improvement to the DCC (destran-coated charcoal) method for determining receptors for 17-beta-oestradiol, 5-alpha-dihydrotestosterone and progesterone in benign and malignant breast conditions, normal glandular tissue and muscular tissue is reported. Preliminary results on 16 malignant cancers and 4 fibrocystic mastopathies are discussed together with a critical review of the technique employed and the results obtained in hormone competition.", "contents": "[Specific cytoplasmic receptors for steroid homones in benign and malignant breast diseases, in normal glandular tissue and pectoral muscle]. An improvement to the DCC (destran-coated charcoal) method for determining receptors for 17-beta-oestradiol, 5-alpha-dihydrotestosterone and progesterone in benign and malignant breast conditions, normal glandular tissue and muscular tissue is reported. Preliminary results on 16 malignant cancers and 4 fibrocystic mastopathies are discussed together with a critical review of the technique employed and the results obtained in hormone competition."}
{"id": "PMID:209378", "title": "Estrogen binding in mammary tissue of C3H mice with or without the mouse mammary tumor virus.", "content": "Substrains of C3H mice, with and without the milk-transmitted form of the mouse mammary tumor virus (MMTV)1, were compared to determine if the presence of MMTV altered estrogen action. Uterine weight response to oral diethylstilbestrol was the same for both substrains, (MMTV+ and MMTV-). The concentration of high-affinity estrogen binding sites (\"receptors\") in lactating mammary tissue did not differ significantly for MMTV+ versus MMTV- mice; the affinity of the estradiol-receptor interaction appeared higher, however, in cytosol from MMTV- mice. Sucrose density gradient analysis revealed no significant differences in sedimentation properties of cytosol receptor from the two substrains.", "contents": "Estrogen binding in mammary tissue of C3H mice with or without the mouse mammary tumor virus. Substrains of C3H mice, with and without the milk-transmitted form of the mouse mammary tumor virus (MMTV)1, were compared to determine if the presence of MMTV altered estrogen action. Uterine weight response to oral diethylstilbestrol was the same for both substrains, (MMTV+ and MMTV-). The concentration of high-affinity estrogen binding sites (\"receptors\") in lactating mammary tissue did not differ significantly for MMTV+ versus MMTV- mice; the affinity of the estradiol-receptor interaction appeared higher, however, in cytosol from MMTV- mice. Sucrose density gradient analysis revealed no significant differences in sedimentation properties of cytosol receptor from the two substrains."}
{"id": "PMID:209379", "title": "Immunotherapy with tumor cells and BCG in the guinea pig, studied by immunological in vivo and in vitro experiments.", "content": "The effect of intradermal immunisation with viable line 1 hepatoma cells and BCG was studied in syngeneic strain 2 guinea pigs. Immunisation with 1.5 X 10(6) hepatoma cells admixed to 200 microgram BCG induced tumor regression in 7/8 animals. Higher or lower doses were less effective and sometimes led to enhanced tumor growth. It appeared that regression or progression of tumors is established as early as 3 weeks after tumor inoculation. Aspects of humoral and cell-mediated tumor immunity in immunised and/or tumor-bearing animals were studied in vitro by the use of mixed cell cultures and of cytotoxicity tests. Immunised tumor-bearing animals reacted more vigorously than those from non-immunised animals when the tumor was small. With increasing tumor volume the specific tumor immunity disappeared in both immunised and non-immunised animals. Sera obtained from immunised or regressor animals were cytotoxic and partially blocked the mixed cell interaction. Sera obtained from progressor animals were neither cytotoxic and nor did they block the mixed cell interaction. Cytotoxic activities resided within immunoglobulin fractions enriched in IgG1 or IgG2, whereas blocking activity was mainly associated with IgG2. The effector cell function was not inhibited by the immunoglobulin fractions tested. In the discussion it is suggested that the ratio of IgG1 and IgG2 antibodies elicited during immune treatment may critically influence the success or failure of immunotherapy.", "contents": "Immunotherapy with tumor cells and BCG in the guinea pig, studied by immunological in vivo and in vitro experiments. The effect of intradermal immunisation with viable line 1 hepatoma cells and BCG was studied in syngeneic strain 2 guinea pigs. Immunisation with 1.5 X 10(6) hepatoma cells admixed to 200 microgram BCG induced tumor regression in 7/8 animals. Higher or lower doses were less effective and sometimes led to enhanced tumor growth. It appeared that regression or progression of tumors is established as early as 3 weeks after tumor inoculation. Aspects of humoral and cell-mediated tumor immunity in immunised and/or tumor-bearing animals were studied in vitro by the use of mixed cell cultures and of cytotoxicity tests. Immunised tumor-bearing animals reacted more vigorously than those from non-immunised animals when the tumor was small. With increasing tumor volume the specific tumor immunity disappeared in both immunised and non-immunised animals. Sera obtained from immunised or regressor animals were cytotoxic and partially blocked the mixed cell interaction. Sera obtained from progressor animals were neither cytotoxic and nor did they block the mixed cell interaction. Cytotoxic activities resided within immunoglobulin fractions enriched in IgG1 or IgG2, whereas blocking activity was mainly associated with IgG2. The effector cell function was not inhibited by the immunoglobulin fractions tested. In the discussion it is suggested that the ratio of IgG1 and IgG2 antibodies elicited during immune treatment may critically influence the success or failure of immunotherapy."}
{"id": "PMID:209380", "title": "[Expression of paternal genes controlling cytochrome oxidase activity in hybrid fish].", "content": "The heat resistance of the oxygen consumption by the mitochondria, temperature dependence of the Michaelis' constant (CM) and heat resistance of cytochrome oxidase were studied in the embryos and larvae of fish hybrids (Misgurnus X Brachydanio). The oxygen consumption by the mitochondria from the larvae of Misgurnus ceased (following the 10 min heating) at 50 degrees, from Brachydanio at 54 degrees and from the hybrids at 52 degress suggesting control of the respiratory function. CM of cytochrome oxidase has the same minimum in the larvae of Misgurnus and Brachydanio, therefore this criterion was not used to study the genetic control in their hybrids. The heat resistance of cytochrome oxidase (T50) differed in Misgurnus and Brachydanio and was of intermediate value in their hybrids. At the early stages of hybrid development T50 was of maternal type (Misgurnus) but beginning from the mid-gastrula stage T50 increased and attained the maximum prior to the hatching. Chloramphenicol did not affect the increase of T50 in hybrids, but actinomycin decreased it almost down to the level characteristic of Misgurnus. The data obtained suggest that the genetic control of cytochrome oxidase activity begins earlier than that of other studied enzymes.", "contents": "[Expression of paternal genes controlling cytochrome oxidase activity in hybrid fish]. The heat resistance of the oxygen consumption by the mitochondria, temperature dependence of the Michaelis' constant (CM) and heat resistance of cytochrome oxidase were studied in the embryos and larvae of fish hybrids (Misgurnus X Brachydanio). The oxygen consumption by the mitochondria from the larvae of Misgurnus ceased (following the 10 min heating) at 50 degrees, from Brachydanio at 54 degrees and from the hybrids at 52 degress suggesting control of the respiratory function. CM of cytochrome oxidase has the same minimum in the larvae of Misgurnus and Brachydanio, therefore this criterion was not used to study the genetic control in their hybrids. The heat resistance of cytochrome oxidase (T50) differed in Misgurnus and Brachydanio and was of intermediate value in their hybrids. At the early stages of hybrid development T50 was of maternal type (Misgurnus) but beginning from the mid-gastrula stage T50 increased and attained the maximum prior to the hatching. Chloramphenicol did not affect the increase of T50 in hybrids, but actinomycin decreased it almost down to the level characteristic of Misgurnus. The data obtained suggest that the genetic control of cytochrome oxidase activity begins earlier than that of other studied enzymes."}
{"id": "PMID:209381", "title": "Biochemical effects of formocresol on bovine pulp tissue.", "content": "Calf pulp was treated with full-strength formocresol, diluted formocresol, or saline for 4 hours. After washing and homogenization, the water extractable supernates were analyzed for total amino acid, carbohydrate, and hydroxyproline content. Additional samples were tested against trypsin, pepsin, collagenase, and hyaluronidase. Other tissue samples treated with 1/5, 1/10, and 1/25 dilutions of formocresol were subjected to trypsin and collagenase. The control tissue gave 50 per cent more extractable material, which contained over 300 per cent more total amino acids and hydroxyproline but only slightly more carbohydrate than the treated tissue. Formocresol treatment produced an 80 to 90 per cent reduction in reactivity to trypsin, pepsin, and collagenase but little change from hyaluronidase action. The increase in reactivity of the tissue to enzyme hydrolysis paralleled the increase in dilution of formocresol. These results indicate a profound effect on the protein fraction of pulp exposed to full-strength formocresol.", "contents": "Biochemical effects of formocresol on bovine pulp tissue. Calf pulp was treated with full-strength formocresol, diluted formocresol, or saline for 4 hours. After washing and homogenization, the water extractable supernates were analyzed for total amino acid, carbohydrate, and hydroxyproline content. Additional samples were tested against trypsin, pepsin, collagenase, and hyaluronidase. Other tissue samples treated with 1/5, 1/10, and 1/25 dilutions of formocresol were subjected to trypsin and collagenase. The control tissue gave 50 per cent more extractable material, which contained over 300 per cent more total amino acids and hydroxyproline but only slightly more carbohydrate than the treated tissue. Formocresol treatment produced an 80 to 90 per cent reduction in reactivity to trypsin, pepsin, and collagenase but little change from hyaluronidase action. The increase in reactivity of the tissue to enzyme hydrolysis paralleled the increase in dilution of formocresol. These results indicate a profound effect on the protein fraction of pulp exposed to full-strength formocresol."}
{"id": "PMID:209385", "title": "[Perinatal acquired cytomegalovirusinfection with following polyneuritis as a rare complication (author's transl)].", "content": "Case report of a 3 week old baby with polyneuritis caused by perinatal acquired cytomegalovirusinfection. Neurological complications are in the acquired form of cytomegalovirusinfection. In acute paralyses of unknown origin CMV-infection should also be included in diagnostic considerations in childhood.", "contents": "[Perinatal acquired cytomegalovirusinfection with following polyneuritis as a rare complication (author's transl)]. Case report of a 3 week old baby with polyneuritis caused by perinatal acquired cytomegalovirusinfection. Neurological complications are in the acquired form of cytomegalovirusinfection. In acute paralyses of unknown origin CMV-infection should also be included in diagnostic considerations in childhood."}
{"id": "PMID:209392", "title": "Assessment of third trimester choline phosphotransferase activity in uncomplicated human pregnancies.", "content": "CDP--choline:1,2-diglyceride choline phosphotransferase (CPT; EC 2.7.8.2) undergoes a marked surge in activity in human amniotic fluid when assayed from 30 weeks of gestation to term. The activity of this enxyme, plotted against gestational age, follows a highly significant regression correlation from which an equation can be obtained for the prediction of gestational age.", "contents": "Assessment of third trimester choline phosphotransferase activity in uncomplicated human pregnancies. CDP--choline:1,2-diglyceride choline phosphotransferase (CPT; EC 2.7.8.2) undergoes a marked surge in activity in human amniotic fluid when assayed from 30 weeks of gestation to term. The activity of this enxyme, plotted against gestational age, follows a highly significant regression correlation from which an equation can be obtained for the prediction of gestational age."}
{"id": "PMID:209394", "title": "Infections and other maternal factors as risk indicators for congenital malformations: a case-control study with paired serum samples.", "content": "An obstetric population of 48,000 individuals was prospectively followed up for evidence of possible teratogenic factors that might be associated with congenital malformations. Serum samples from 274 mothers of defective children and from paired controls were collected during early pregnancy and approximately one month after delivery and tested for antibodies against ten different viruses, Mycoplasma pneumoniae, and Toxoplasma. These data were supplemented with clinical information on infections, other diseases, drug intake, and other potentially teratogenic factors during pregnancy. Mothers of defective children had more seroconversions (fourfold or greater increase in titer) than the controls, 123 vs. 86. This difference was mainly due to an increase in herpes simplex viruses 1 and 2, cytomegalovirus, varicella-zoster virus, and Toxoplasma titers. In addition, the number of reported diseases during the pregnancy, the intake of drugs (especially analgesics and hormones), and the number of earlier abortions were greater in the mothers of the defective children than in the controls.", "contents": "Infections and other maternal factors as risk indicators for congenital malformations: a case-control study with paired serum samples. An obstetric population of 48,000 individuals was prospectively followed up for evidence of possible teratogenic factors that might be associated with congenital malformations. Serum samples from 274 mothers of defective children and from paired controls were collected during early pregnancy and approximately one month after delivery and tested for antibodies against ten different viruses, Mycoplasma pneumoniae, and Toxoplasma. These data were supplemented with clinical information on infections, other diseases, drug intake, and other potentially teratogenic factors during pregnancy. Mothers of defective children had more seroconversions (fourfold or greater increase in titer) than the controls, 123 vs. 86. This difference was mainly due to an increase in herpes simplex viruses 1 and 2, cytomegalovirus, varicella-zoster virus, and Toxoplasma titers. In addition, the number of reported diseases during the pregnancy, the intake of drugs (especially analgesics and hormones), and the number of earlier abortions were greater in the mothers of the defective children than in the controls."}
{"id": "PMID:209397", "title": "Daytime state and night-time sleep; a sleep study after a marathon group experience.", "content": "The nocturnal sleep of 9 subjects was recorded under two conditions following a \"normal\" weekend and following a weekend in which the subjects participated in a psychodynamic marathon group activity. Differences between the two experimental conditions were found for sleep latency and on one measurement of D-latency. Both latencies were reduced after the marathon group. No differences were found on the remaining 12 measurements. These findings tend to reaffirm the stability of sleep patterns under various pre-sleep conditions.", "contents": "Daytime state and night-time sleep; a sleep study after a marathon group experience. The nocturnal sleep of 9 subjects was recorded under two conditions following a \"normal\" weekend and following a weekend in which the subjects participated in a psychodynamic marathon group activity. Differences between the two experimental conditions were found for sleep latency and on one measurement of D-latency. Both latencies were reduced after the marathon group. No differences were found on the remaining 12 measurements. These findings tend to reaffirm the stability of sleep patterns under various pre-sleep conditions."}
{"id": "PMID:209398", "title": "Dissociation between antidiuretic response and renal medullary cyclic AMP levels in the rat.", "content": "In vivo experiments were performed in male Wistar rats to elucidate the probable relation between renal concentrating ability and medullary cyclic AMP content as influenced by changes of hydration and by administration of antidiuretic hormone (ADH). Cyclic AMP levels were 37% lower in water diuretic than in control animals (P less than 0.01), but were not significantly changed during prolonged antidiuresis induced by dehydration or ADH administration. Nor could any change of cyclic AMP levels be demonstrated between 2 and 20 min after ADH injection. Significant increases of medullary cyclic AMP content occurred following stress, anesthesia, and administration of isoproterenol and 3-isobutyl-1-methylxanthin. The results suggest that the level of cyclic AMP in the renal medulla may not be an important determinant of the antidiuretic response produced by ADH in rats.", "contents": "Dissociation between antidiuretic response and renal medullary cyclic AMP levels in the rat. In vivo experiments were performed in male Wistar rats to elucidate the probable relation between renal concentrating ability and medullary cyclic AMP content as influenced by changes of hydration and by administration of antidiuretic hormone (ADH). Cyclic AMP levels were 37% lower in water diuretic than in control animals (P less than 0.01), but were not significantly changed during prolonged antidiuresis induced by dehydration or ADH administration. Nor could any change of cyclic AMP levels be demonstrated between 2 and 20 min after ADH injection. Significant increases of medullary cyclic AMP content occurred following stress, anesthesia, and administration of isoproterenol and 3-isobutyl-1-methylxanthin. The results suggest that the level of cyclic AMP in the renal medulla may not be an important determinant of the antidiuretic response produced by ADH in rats."}
{"id": "PMID:209400", "title": "[\"Small cell\" carcinoma of the lung. Results obtained using combination chemotherapy (adriamycin, vincristine, cyclophosphamide) in 38 patients (author's transl)].", "content": "A cyclic and sequential combination of adriamycin, vincristine (or VM 26) and cyclophosphamide was used, with a follow up of 4 to 33 months in 38 patients with a \"micro-cellular\" carcinoma of the lung. Radiotherapy was used in association in a variable manner. Chemotherapy alone resulted in marked regression of the lesions (regression is greater than 50%) in approximately 65 per cent of cases and a level of complete regression which varied from 31 to 45 per cent according to the degree of diffusion of the lesions at the time of admission. In this study, survival in apparently localised forms was 70 per cent after one year and 55 per cent at eighteen months, whilst it was 34 per cent at one year and nil at eighteen months in patients with evidence of metastatic disease at the time of entry. These encouraging results indicate a hope for improvement, in certain patients reacting favourably to this protocol, in the still grave prognosis of \"small cell\" carcinoma of the lung.", "contents": "[\"Small cell\" carcinoma of the lung. Results obtained using combination chemotherapy (adriamycin, vincristine, cyclophosphamide) in 38 patients (author's transl)]. A cyclic and sequential combination of adriamycin, vincristine (or VM 26) and cyclophosphamide was used, with a follow up of 4 to 33 months in 38 patients with a \"micro-cellular\" carcinoma of the lung. Radiotherapy was used in association in a variable manner. Chemotherapy alone resulted in marked regression of the lesions (regression is greater than 50%) in approximately 65 per cent of cases and a level of complete regression which varied from 31 to 45 per cent according to the degree of diffusion of the lesions at the time of admission. In this study, survival in apparently localised forms was 70 per cent after one year and 55 per cent at eighteen months, whilst it was 34 per cent at one year and nil at eighteen months in patients with evidence of metastatic disease at the time of entry. These encouraging results indicate a hope for improvement, in certain patients reacting favourably to this protocol, in the still grave prognosis of \"small cell\" carcinoma of the lung."}
{"id": "PMID:209399", "title": "A comparative study of the cardiac troponin inhibitory factor (TNI) from mammalians.", "content": "Troponin inhibitory factor, TNI, was prepared by affinity chromatography from different mammalian hearts. (i) Structure. These different TNI have the same M.W. (28000), which is higher than that found in rabbit skeletal muscle (23000). Nevertheless they differ with respect of their charge as shown by alkaline urea polyacrylamide gel electrophoresis using cardiac TNI which has previously been bound to an excess of skeletal troponin Ca2+-binding factor. These changes do not correlate with the PO4 content of TNI. They are associated with structural differences demonstrated by peptide mapping of the unfolded molecule after papain treatment. The structure of cardiac TNI from rat and rabbit differs clearly from that of crow and pig. (ii) Biological activity. These different TNI have the same inhibitory effect on skeletal actomyosin. ATPase, the same content of PO4 and the same ability to be phosphorylated in-vitro by a bovine heart c-AMP-dependent protein kinase.", "contents": "A comparative study of the cardiac troponin inhibitory factor (TNI) from mammalians. Troponin inhibitory factor, TNI, was prepared by affinity chromatography from different mammalian hearts. (i) Structure. These different TNI have the same M.W. (28000), which is higher than that found in rabbit skeletal muscle (23000). Nevertheless they differ with respect of their charge as shown by alkaline urea polyacrylamide gel electrophoresis using cardiac TNI which has previously been bound to an excess of skeletal troponin Ca2+-binding factor. These changes do not correlate with the PO4 content of TNI. They are associated with structural differences demonstrated by peptide mapping of the unfolded molecule after papain treatment. The structure of cardiac TNI from rat and rabbit differs clearly from that of crow and pig. (ii) Biological activity. These different TNI have the same inhibitory effect on skeletal actomyosin. ATPase, the same content of PO4 and the same ability to be phosphorylated in-vitro by a bovine heart c-AMP-dependent protein kinase."}
{"id": "PMID:209403", "title": "[Epidemiology of primary bronchus cancer from which the African Negro suffers (author's transl)].", "content": "The study of 86 cases collected along 5 years regarding the primary bronchus cancer from which the African Negro in Abidjan suffers, points out the recent increase of this pathology, the predominating epidermolid histological type, the fact that men reaching a critical age of 45 years old are mostly concerned and especially those living in the rural areas. Because of the absence of industrial pollution and occupational exposure in Ivory Coast, the very important relation between bronchus carcinoma and smoking cigarettes is suggested.", "contents": "[Epidemiology of primary bronchus cancer from which the African Negro suffers (author's transl)]. The study of 86 cases collected along 5 years regarding the primary bronchus cancer from which the African Negro in Abidjan suffers, points out the recent increase of this pathology, the predominating epidermolid histological type, the fact that men reaching a critical age of 45 years old are mostly concerned and especially those living in the rural areas. Because of the absence of industrial pollution and occupational exposure in Ivory Coast, the very important relation between bronchus carcinoma and smoking cigarettes is suggested."}
{"id": "PMID:209405", "title": "Cytomegalovirus infection in malignant blood diseases:clinical and laboratory data in 29 patients.", "content": "Twenty-nine patients treated for malignant blood diseases developped CMV infection. Their clinical and laboratory features were studied. The results indicated that this infection apparently did not influence the prognisis of the underlying disease. The main hematological feature was pancytopenia. The data of viremia suggested active infection. A marked increase of CMV CF antibodies were observed in 27/29 patients, and the peak titers of 42% of our cases were greater than 1:1024. Homogenous Ig were detected in 7/29 patient's serum.", "contents": "Cytomegalovirus infection in malignant blood diseases:clinical and laboratory data in 29 patients. Twenty-nine patients treated for malignant blood diseases developped CMV infection. Their clinical and laboratory features were studied. The results indicated that this infection apparently did not influence the prognisis of the underlying disease. The main hematological feature was pancytopenia. The data of viremia suggested active infection. A marked increase of CMV CF antibodies were observed in 27/29 patients, and the peak titers of 42% of our cases were greater than 1:1024. Homogenous Ig were detected in 7/29 patient's serum."}
{"id": "PMID:209406", "title": "Binding of phosphorylated histone H1 to DNA.", "content": "A chromatin associated protein kinase was used to add 3 moles of phosphate to seryl side chains of 1 mole of histone H1. The DNA binding properties of this in vitro phosphorylated H1 were compared with those of unmodified H1. Considerably more radioactive superhelical DNA was retained on nitrocellulose filters at 20mM-40mM NaCl by phosphorylated H1 than by unmodified H1. However, zone velocity sedimentation analysis of histone-DNA complexes indicated that similar amounts of phosphorylated and unmodified H1 are bound to DNA. It is therefore concluded that phosphorylated H1 binds distributively to many or all DNA molecules available (depending on the histone/DNA ratio) while unmodified H1 binds cooperatively to a fraction of the DNA molecules in the reaction mixture.", "contents": "Binding of phosphorylated histone H1 to DNA. A chromatin associated protein kinase was used to add 3 moles of phosphate to seryl side chains of 1 mole of histone H1. The DNA binding properties of this in vitro phosphorylated H1 were compared with those of unmodified H1. Considerably more radioactive superhelical DNA was retained on nitrocellulose filters at 20mM-40mM NaCl by phosphorylated H1 than by unmodified H1. However, zone velocity sedimentation analysis of histone-DNA complexes indicated that similar amounts of phosphorylated and unmodified H1 are bound to DNA. It is therefore concluded that phosphorylated H1 binds distributively to many or all DNA molecules available (depending on the histone/DNA ratio) while unmodified H1 binds cooperatively to a fraction of the DNA molecules in the reaction mixture."}
{"id": "PMID:209407", "title": "Characterization of the mRNA for herpes simplex virus thymidine kinase by cell-free synthesis of active enzyme.", "content": "The cytoplasmic mRNA which codes for the herpes simplex virus specific thymidine kinase (TK) is polyadenylated and is 14.5s in size. This corresponds to an RNA of 1400 nucleotides. The TK polypeptide is about 42,000 daltons, which requires 1100 nucleotide. We conclude that the cytoplasmic mRNA is monocistronic. The reticulocyte lysate cell-free translation system synthesizes enzymatically active HSV-TK which can be assayed with high specificity and sensitivity by use of 125I-iododeoxycytidine as a substrate.", "contents": "Characterization of the mRNA for herpes simplex virus thymidine kinase by cell-free synthesis of active enzyme. The cytoplasmic mRNA which codes for the herpes simplex virus specific thymidine kinase (TK) is polyadenylated and is 14.5s in size. This corresponds to an RNA of 1400 nucleotides. The TK polypeptide is about 42,000 daltons, which requires 1100 nucleotide. We conclude that the cytoplasmic mRNA is monocistronic. The reticulocyte lysate cell-free translation system synthesizes enzymatically active HSV-TK which can be assayed with high specificity and sensitivity by use of 125I-iododeoxycytidine as a substrate."}
{"id": "PMID:209408", "title": "Localization of the 5' terminus of late SV40 mRNA.", "content": "A cap-containing oligonucleotide has been isolated from a T1 ribonuclease hydrolysate of total Simian Virus 40-specific late RNA and its structure has been determined as 7mG(5')ppp(5') mAmpU(m)pUp(Up,Cp)ApGp. This oligonucleotide constitutes the major 5' terminus of both late mRNA species, 16S and 19S. Assuming that viral mRNA \"caps\" are derived from a 5'-terminal triphosphate or diphosphate, these results mean that late transcription is (mainly) initiated at nucleotide L 308 (numbering system of Simian Virus 40 DNA, cf. Fiers et al. (1978) Nature, 273, 113-120). The cap is followed by a contiguous leader sequence which is at least 194 nucleotides long.", "contents": "Localization of the 5' terminus of late SV40 mRNA. A cap-containing oligonucleotide has been isolated from a T1 ribonuclease hydrolysate of total Simian Virus 40-specific late RNA and its structure has been determined as 7mG(5')ppp(5') mAmpU(m)pUp(Up,Cp)ApGp. This oligonucleotide constitutes the major 5' terminus of both late mRNA species, 16S and 19S. Assuming that viral mRNA \"caps\" are derived from a 5'-terminal triphosphate or diphosphate, these results mean that late transcription is (mainly) initiated at nucleotide L 308 (numbering system of Simian Virus 40 DNA, cf. Fiers et al. (1978) Nature, 273, 113-120). The cap is followed by a contiguous leader sequence which is at least 194 nucleotides long."}
{"id": "PMID:209409", "title": "A rapid method for the measurement of the unwinding angle of intercalating agents and the superhelix density of circular DNAs.", "content": "By incubating covalently-closed circular DNA in the presence of calf thymus topoisomerase and unwinding ligands (intercalating drugs and proteins) DNAs of different superhelix density can be produced. These changes in superhelix density can be monitored by an ethidium fluorescence assay, since the level of ethidium binding varies with the superhelix density of a DNA. Thus the equivalence point, in a titration between an unwinding ligand and a supercoiled DNA, can be found. This forms the basis for an extremely rapid method for measuring unwinding angles and superhelix densities. Results are presented which agree well with those reported by previous authors using different techniques. The present method compares very favourably with others when evaluated in terms of rapidity, cost of materials, cost of equipment, accuracy and also applicability.", "contents": "A rapid method for the measurement of the unwinding angle of intercalating agents and the superhelix density of circular DNAs. By incubating covalently-closed circular DNA in the presence of calf thymus topoisomerase and unwinding ligands (intercalating drugs and proteins) DNAs of different superhelix density can be produced. These changes in superhelix density can be monitored by an ethidium fluorescence assay, since the level of ethidium binding varies with the superhelix density of a DNA. Thus the equivalence point, in a titration between an unwinding ligand and a supercoiled DNA, can be found. This forms the basis for an extremely rapid method for measuring unwinding angles and superhelix densities. Results are presented which agree well with those reported by previous authors using different techniques. The present method compares very favourably with others when evaluated in terms of rapidity, cost of materials, cost of equipment, accuracy and also applicability."}
{"id": "PMID:209410", "title": "Relation of cell type and cell density in tissue culture to the isoaccepting spectra of the nucleoside Q containing tRNAs: tRNATyr, tRNAHis, tRNAAsn and tRNAAsp.", "content": "An examination, using reversed-phase chromatography and cyanogen bromide treatment, of tRNATyr, tRNAHis, tRNAAsn, and tRNAAsp from SV40-transformed mouse fibroblasts grown to different cell densities, untransformed cells grown to confluence, and mouse liver indicates that: (1) The tissue cultured mouse fibroblasts examined here are hypomodified with respect to nucleoside Q, while liver tRNA is almost completely modified with respect to Q. (2) Cell density and/or proliferative state do not present as major variables in controlling the expression of Q in the present system. (3) SV40 virus transformation is not a major variable controlling the expression of Q in the present system. The present results support previous use of cyanogen bromide effected shifts in chromatographic elution as an assay for nucleoside Q.", "contents": "Relation of cell type and cell density in tissue culture to the isoaccepting spectra of the nucleoside Q containing tRNAs: tRNATyr, tRNAHis, tRNAAsn and tRNAAsp. An examination, using reversed-phase chromatography and cyanogen bromide treatment, of tRNATyr, tRNAHis, tRNAAsn, and tRNAAsp from SV40-transformed mouse fibroblasts grown to different cell densities, untransformed cells grown to confluence, and mouse liver indicates that: (1) The tissue cultured mouse fibroblasts examined here are hypomodified with respect to nucleoside Q, while liver tRNA is almost completely modified with respect to Q. (2) Cell density and/or proliferative state do not present as major variables in controlling the expression of Q in the present system. (3) SV40 virus transformation is not a major variable controlling the expression of Q in the present system. The present results support previous use of cyanogen bromide effected shifts in chromatographic elution as an assay for nucleoside Q."}
{"id": "PMID:209411", "title": "Okazaki pieces grow opposite to the replication fork direction during simian virus 40 DNA replication.", "content": "Simian virus 40 replicating DNA was pulse labeled with alpha-32P-dATP using an acellular DNA replication system. Nascent DNA chains of less than 200 nucleotides (Okazaki pieces) were then isolated from the denatured replicating DNA by electrosieving through a polyacrylamide gel column. The purified Okazaki pieces were hybridized to separated strands of Bg1(1)+Hpa1 simian virus 40 DNA restriction fragments immobilized on nitrocellulose filters. Only strands with polarity of the DNA replication fork direction hybridized with Okazaki pieces. Hence, Okazaki pieces in simian virus 40 are synthesized against the DNA replication fork direction.", "contents": "Okazaki pieces grow opposite to the replication fork direction during simian virus 40 DNA replication. Simian virus 40 replicating DNA was pulse labeled with alpha-32P-dATP using an acellular DNA replication system. Nascent DNA chains of less than 200 nucleotides (Okazaki pieces) were then isolated from the denatured replicating DNA by electrosieving through a polyacrylamide gel column. The purified Okazaki pieces were hybridized to separated strands of Bg1(1)+Hpa1 simian virus 40 DNA restriction fragments immobilized on nitrocellulose filters. Only strands with polarity of the DNA replication fork direction hybridized with Okazaki pieces. Hence, Okazaki pieces in simian virus 40 are synthesized against the DNA replication fork direction."}
{"id": "PMID:209412", "title": "Alterations in chromatin of cells infected with RNA tumor viruses.", "content": "Chromatins were isolated from murine leukemia or sarcoma virus infected lymphocyte-like TB cells and compared by immunological and biochemical methods. Chromatin from virus infected cells did not fix complement as well as uninfected cell chromatin suggesting that conformational changes had occurred in chromatin from virus infected cells. This alteration was detected within 24 hours after infection. Infected cell chromatins, examined by electrophoretic methods after radiolabeling displayed alterations in nonhistone proteins, whereas the histones appeared unaltered. The non-histones were synthesized in greater amounts in infected compared to normal cells, particularly a 60,000 D protein, while the amount of histone did not vary. The above changes should not have been due to cell growth or cycle variations, for the cells had similar growth rates and were harvested from the same stage of cell confluency during exponential growth to ensure uniformity of culture conditions.", "contents": "Alterations in chromatin of cells infected with RNA tumor viruses. Chromatins were isolated from murine leukemia or sarcoma virus infected lymphocyte-like TB cells and compared by immunological and biochemical methods. Chromatin from virus infected cells did not fix complement as well as uninfected cell chromatin suggesting that conformational changes had occurred in chromatin from virus infected cells. This alteration was detected within 24 hours after infection. Infected cell chromatins, examined by electrophoretic methods after radiolabeling displayed alterations in nonhistone proteins, whereas the histones appeared unaltered. The non-histones were synthesized in greater amounts in infected compared to normal cells, particularly a 60,000 D protein, while the amount of histone did not vary. The above changes should not have been due to cell growth or cycle variations, for the cells had similar growth rates and were harvested from the same stage of cell confluency during exponential growth to ensure uniformity of culture conditions."}
{"id": "PMID:209414", "title": "The nursing care of lung cancer patients: emphasizing chemotherapy.", "content": "The experience of coping with lung cancer--from diagnosis to treatment to inevitable death--is indescribably difficult for the cancer patient. The nurse, with her basic knowledge of the disease process, diagnosis, prognosis, and treatment, and by employing her sensitivity to the patient's emotional needs, can ease the pain of this experience. The nurse must use her technical knowledge and understanding to provide the patient with the knowledge he needs to participate in his own care as well as the emotional strength to deal with the physiologic strains of the disease.", "contents": "The nursing care of lung cancer patients: emphasizing chemotherapy. The experience of coping with lung cancer--from diagnosis to treatment to inevitable death--is indescribably difficult for the cancer patient. The nurse, with her basic knowledge of the disease process, diagnosis, prognosis, and treatment, and by employing her sensitivity to the patient's emotional needs, can ease the pain of this experience. The nurse must use her technical knowledge and understanding to provide the patient with the knowledge he needs to participate in his own care as well as the emotional strength to deal with the physiologic strains of the disease."}
{"id": "PMID:209427", "title": "[Mediastinal surgery in children].", "content": "From 96 surgical interventions in the child, the authors studied the repartition of tumours according to their histological nature, their benignity or malignancy. For each kind of tumour they gave its frequency and clinical, radiological and biological data. Above all they studied the distant results of these interventions with an important set back. The results are excellent for benign tumours and promising for malignant ones and enable the deduction of therapeutical indications.", "contents": "[Mediastinal surgery in children]. From 96 surgical interventions in the child, the authors studied the repartition of tumours according to their histological nature, their benignity or malignancy. For each kind of tumour they gave its frequency and clinical, radiological and biological data. Above all they studied the distant results of these interventions with an important set back. The results are excellent for benign tumours and promising for malignant ones and enable the deduction of therapeutical indications."}
{"id": "PMID:209428", "title": "[One case of severe tracheobronchopathy with immune depression : herpetic disease?].", "content": "The authors report a case of severe obliterating laryngo-tracheo-bronchitis without any evident etiology in a young patient with depressed immunity. A herpetic virus was isolated by distal bronchial brushing and by larynx biopsy. The level of specific antibodies rose significantly. These facts together with the clinical history and unsuccessful microbiological searches, suggest the herpetic nature of this affection, albeit exceptional. At this opportunity, a review of the literature is presented showing the imprecision of diagnostic criteria in this field of pathology.", "contents": "[One case of severe tracheobronchopathy with immune depression : herpetic disease?]. The authors report a case of severe obliterating laryngo-tracheo-bronchitis without any evident etiology in a young patient with depressed immunity. A herpetic virus was isolated by distal bronchial brushing and by larynx biopsy. The level of specific antibodies rose significantly. These facts together with the clinical history and unsuccessful microbiological searches, suggest the herpetic nature of this affection, albeit exceptional. At this opportunity, a review of the literature is presented showing the imprecision of diagnostic criteria in this field of pathology."}
{"id": "PMID:209429", "title": "Effect of dietary aflatoxin on vitamin D3 metabolism in chicks.", "content": "Male broiler chicks were fed diets containing either O (control) or 2.5 p.p.m. aflatoxin (toxin) for four weeks. A group of eight birds fed each diet was infected intravenously with radioactive vitamin D3 (D3) and a second group with radioactive 25-hydroxy vitamin D3 (25-OH D3). Plasma was obtained 24 hr. after dosing with D3 and 6 hr. after dosing with 25-OH D3. The vitamin D metabolites were extracted from the plasma an chromatographed on Sephadex LH-20 for separation. The four peaks of radioactivity separated corresponded to D3, 25-OH D3, 24,25-dihydroxy vitamin D3 (24,25-(OH)2D3) and 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3). Percentages of radiation in each peak were (1) controls given D3--6.55, 64.30, 5.94 and 4.04; (2) toxin given D3--10.05, 56.96, 8.95 and 4.68; (3) control given 25-OHD3-2.16, 85.80, 4.11 and 2.04; and (4) toxin given 25-OH D3--1.53, 79.84, 5.56 and 2.14. The only significant differences between the control and toxin groups were in D3 and 24,25-(OH)2D3 in chicks given D3. Even these changes were small and the data would suggest that feeding 2.5 p.p.m. aflatoxin for four weeks does not greatly alter vitamin D metabolism.", "contents": "Effect of dietary aflatoxin on vitamin D3 metabolism in chicks. Male broiler chicks were fed diets containing either O (control) or 2.5 p.p.m. aflatoxin (toxin) for four weeks. A group of eight birds fed each diet was infected intravenously with radioactive vitamin D3 (D3) and a second group with radioactive 25-hydroxy vitamin D3 (25-OH D3). Plasma was obtained 24 hr. after dosing with D3 and 6 hr. after dosing with 25-OH D3. The vitamin D metabolites were extracted from the plasma an chromatographed on Sephadex LH-20 for separation. The four peaks of radioactivity separated corresponded to D3, 25-OH D3, 24,25-dihydroxy vitamin D3 (24,25-(OH)2D3) and 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3). Percentages of radiation in each peak were (1) controls given D3--6.55, 64.30, 5.94 and 4.04; (2) toxin given D3--10.05, 56.96, 8.95 and 4.68; (3) control given 25-OHD3-2.16, 85.80, 4.11 and 2.04; and (4) toxin given 25-OH D3--1.53, 79.84, 5.56 and 2.14. The only significant differences between the control and toxin groups were in D3 and 24,25-(OH)2D3 in chicks given D3. Even these changes were small and the data would suggest that feeding 2.5 p.p.m. aflatoxin for four weeks does not greatly alter vitamin D metabolism."}
{"id": "PMID:209430", "title": "Vaccination immunity to selected diseases in chickens fed the androgen analog mibolerone.", "content": "Chickens fed the androgen analog mibolerone during the first 7 weeks of life regress their bursa of Fabricius but can be properly immunized by vaccination against avian pathogens of major economic importance such as Newcastle disease virus, infectious laryngotracheitis virus, avian encephalomyelitis virus, infectious bronchitis virus, fowl pox virus, Marek's disease virus, and Pasteurella multocida, the pathogen causing fowl cholera. These findings on immunocompetence to infectious agents are important because we have previously shown that the administration of mibolerone prevents the development of lymphoid leukosis tumors.", "contents": "Vaccination immunity to selected diseases in chickens fed the androgen analog mibolerone. Chickens fed the androgen analog mibolerone during the first 7 weeks of life regress their bursa of Fabricius but can be properly immunized by vaccination against avian pathogens of major economic importance such as Newcastle disease virus, infectious laryngotracheitis virus, avian encephalomyelitis virus, infectious bronchitis virus, fowl pox virus, Marek's disease virus, and Pasteurella multocida, the pathogen causing fowl cholera. These findings on immunocompetence to infectious agents are important because we have previously shown that the administration of mibolerone prevents the development of lymphoid leukosis tumors."}
{"id": "PMID:209431", "title": "Differentiation of progressive versus regressive Rous virus-induced avian sarcomas according to tumor and infiltrating lymphocyte fine structure.", "content": "Electron microscope examination of progressing and regressing Rous virus-induced sarcomas in an inbred line of White Leghorns revealed that regressing tumors contained moderate to marked lymphocyte infiltration, frequent contact between lymphocytes and tumor cells, and extensive areas of necrosis. Lymphocytes infiltrating regressing tumors exhibited a polar accumulation of organelles at the point of contact between lymphocyte and target cell. On the other hand, progressing tumors contained low to moderate numbers of lymphocytes, infrequent lymphocyte-tumor cell interaction and less evidence of tumor cell degeneration. Lymphocytes from progressing tumors lacked the polar organization of organelles. This experimental system is offered as a means of studying the role of lymphocytes in tumor regression.", "contents": "Differentiation of progressive versus regressive Rous virus-induced avian sarcomas according to tumor and infiltrating lymphocyte fine structure. Electron microscope examination of progressing and regressing Rous virus-induced sarcomas in an inbred line of White Leghorns revealed that regressing tumors contained moderate to marked lymphocyte infiltration, frequent contact between lymphocytes and tumor cells, and extensive areas of necrosis. Lymphocytes infiltrating regressing tumors exhibited a polar accumulation of organelles at the point of contact between lymphocyte and target cell. On the other hand, progressing tumors contained low to moderate numbers of lymphocytes, infrequent lymphocyte-tumor cell interaction and less evidence of tumor cell degeneration. Lymphocytes from progressing tumors lacked the polar organization of organelles. This experimental system is offered as a means of studying the role of lymphocytes in tumor regression."}
{"id": "PMID:209432", "title": "Lymphocytotoxicity of chickens bearing Rous sarcomas.", "content": "A 51Cr uptake microcytotoxicity assay was used to determine the cytotoxicity of lymphocytes from chickens bearing Rous sarcomas. Differences in lymphocyte cytotoxicity among individual chickens were statistically significant. Lymphocytes from chickens regressing (or having regressed) their tumors were significantly more cytotoxic than lymphocytes from hosts with progressing tumors. Lymphocytes from chickens with progressing tumors tended to enhance tumor cell growth in vitro.", "contents": "Lymphocytotoxicity of chickens bearing Rous sarcomas. A 51Cr uptake microcytotoxicity assay was used to determine the cytotoxicity of lymphocytes from chickens bearing Rous sarcomas. Differences in lymphocyte cytotoxicity among individual chickens were statistically significant. Lymphocytes from chickens regressing (or having regressed) their tumors were significantly more cytotoxic than lymphocytes from hosts with progressing tumors. Lymphocytes from chickens with progressing tumors tended to enhance tumor cell growth in vitro."}
{"id": "PMID:209433", "title": "Vaccination against infectious bronchitis and the immunosuppressive effects of infectious bursal disease.", "content": "An immunosuppressive effect was demonstrated in chickens which were infected with infectious bursal disease virus (IBDV) early in life and prior to or shortly after vaccination with infectious bronchitis virus (IBV). This effect was evident by an increased susceptibility to respiratory tract infection with IBV and reduced virus-serum neutralizing antibody levels. Chickens which were hatched from dams susceptible to infectious bursal disease (IBD) were less responsive to IBV immunization attempts, if exposed to IBDV, than were those individuals hatched from IBD immune dams. However, in some cases, chickens from IBD immune dams were also more susceptible to IBV challenge when they had been exposed to IBDV and when compared to birds unexposed to IBDV but vaccinated against IB. An effect of cyclophosphamide on the bursa of Fabricius also had an immunosuppressive action on IBV immunity which was similar to the results from IBDV exposure. The data engendered from these trials may explain the unsatisfactory immunity sometimes observed under field conditions when broilers and replacement pullets are vaccinated at an early age.", "contents": "Vaccination against infectious bronchitis and the immunosuppressive effects of infectious bursal disease. An immunosuppressive effect was demonstrated in chickens which were infected with infectious bursal disease virus (IBDV) early in life and prior to or shortly after vaccination with infectious bronchitis virus (IBV). This effect was evident by an increased susceptibility to respiratory tract infection with IBV and reduced virus-serum neutralizing antibody levels. Chickens which were hatched from dams susceptible to infectious bursal disease (IBD) were less responsive to IBV immunization attempts, if exposed to IBDV, than were those individuals hatched from IBD immune dams. However, in some cases, chickens from IBD immune dams were also more susceptible to IBV challenge when they had been exposed to IBDV and when compared to birds unexposed to IBDV but vaccinated against IB. An effect of cyclophosphamide on the bursa of Fabricius also had an immunosuppressive action on IBV immunity which was similar to the results from IBDV exposure. The data engendered from these trials may explain the unsatisfactory immunity sometimes observed under field conditions when broilers and replacement pullets are vaccinated at an early age."}
{"id": "PMID:209434", "title": "Monensin, Eimeria tenella infection, and effects on the bacterial populations in the ceca of gnotobiotic chickens.", "content": "Bacteria-free chicks in separate plastic film isolators were inoculated orally with single species of bacteria. Within an isolator, half the birds were fed unmedicated feed and half received feed containing 100 ppm monensin. With clostridium perfringens as the established species of monoflora, bacterial counts from the duodenum were 10(4) times lower and counts from the ceca were three times lower in monensin-fed birds compared to unmedicated birds. Infection with Eimeria tenella stimulated an eight-fold increase in the numbers of C. perfringens in the ceca of unmedicated birds but no increase in monensin-fed birds. With Bacteroides sp. or Streptococcus faecalis as monoflora, there was no difference in the cecal or duodenal populations between medicated and unmedicated birds uninfected with coccidia. In contrast to C. perfringens, populations of Bacteroides sp. and S. faecalis in the ceca decreased five to 100-fold in both medicated and unmedicated chicks after infection with E. tenella. Duodenal populations of C. perfringens, Bacteroides sp., and S. faecalis were unaffected by the coccidial infection.", "contents": "Monensin, Eimeria tenella infection, and effects on the bacterial populations in the ceca of gnotobiotic chickens. Bacteria-free chicks in separate plastic film isolators were inoculated orally with single species of bacteria. Within an isolator, half the birds were fed unmedicated feed and half received feed containing 100 ppm monensin. With clostridium perfringens as the established species of monoflora, bacterial counts from the duodenum were 10(4) times lower and counts from the ceca were three times lower in monensin-fed birds compared to unmedicated birds. Infection with Eimeria tenella stimulated an eight-fold increase in the numbers of C. perfringens in the ceca of unmedicated birds but no increase in monensin-fed birds. With Bacteroides sp. or Streptococcus faecalis as monoflora, there was no difference in the cecal or duodenal populations between medicated and unmedicated birds uninfected with coccidia. In contrast to C. perfringens, populations of Bacteroides sp. and S. faecalis in the ceca decreased five to 100-fold in both medicated and unmedicated chicks after infection with E. tenella. Duodenal populations of C. perfringens, Bacteroides sp., and S. faecalis were unaffected by the coccidial infection."}
{"id": "PMID:209437", "title": "A comparative pathogenesis of two Mareks disease virus isolates.", "content": "The pathogenesis of the JM and GA isolates of Marek's disease virus (MDV) infection was compared by studying the sequential tissue distribution of MDV associated antigens with gross and microscopic lesions in infected chickens. With both MDV isolates the initial sites of viral replication were the lymphoid organs, skin, and featers. Both the GA and JM isolates were viscerotropic as demonstrated by the presence of MDV antigens with gross and microscopic changes occurring in several visceral organs. The JM isolate was more neurotropic and had a greater affinity for the gonads than the GA isolates as evidenced by an early detection of MDV antigens and severe pathology in the peripheral nerves and gonads.", "contents": "A comparative pathogenesis of two Mareks disease virus isolates. The pathogenesis of the JM and GA isolates of Marek's disease virus (MDV) infection was compared by studying the sequential tissue distribution of MDV associated antigens with gross and microscopic lesions in infected chickens. With both MDV isolates the initial sites of viral replication were the lymphoid organs, skin, and featers. Both the GA and JM isolates were viscerotropic as demonstrated by the presence of MDV antigens with gross and microscopic changes occurring in several visceral organs. The JM isolate was more neurotropic and had a greater affinity for the gonads than the GA isolates as evidenced by an early detection of MDV antigens and severe pathology in the peripheral nerves and gonads."}
{"id": "PMID:209438", "title": "[Effect of amino acids on the beta-aspartokinase activity from Corynebacterium glutamicum of wild and mutant strains].", "content": "The effect of amino acids, their structural analogs and ammonium sulphate on the enzyme activity of beta-aspartokinase isolated from Corynebacterium glutamicum was studied. Two strains were used: one of the wild type and the other--a mutant strain whose growth remains uninhibited by a simultaneous addition of threonine and S-2-aminoethylcysteine, a lysine analog. Significant differences in the effect of amino acids and their analogs on the beta-aspartokinase activity of the parental and mutant strains were detected. These findings suggest that the lysine supersynthesis by the mutant strain of Corynebacterium glutamicum occurs due to genetically induced changes of allosteric properties of the mutant enzyme.", "contents": "[Effect of amino acids on the beta-aspartokinase activity from Corynebacterium glutamicum of wild and mutant strains]. The effect of amino acids, their structural analogs and ammonium sulphate on the enzyme activity of beta-aspartokinase isolated from Corynebacterium glutamicum was studied. Two strains were used: one of the wild type and the other--a mutant strain whose growth remains uninhibited by a simultaneous addition of threonine and S-2-aminoethylcysteine, a lysine analog. Significant differences in the effect of amino acids and their analogs on the beta-aspartokinase activity of the parental and mutant strains were detected. These findings suggest that the lysine supersynthesis by the mutant strain of Corynebacterium glutamicum occurs due to genetically induced changes of allosteric properties of the mutant enzyme."}
{"id": "PMID:209439", "title": "[Separation and purification of isoenzymes of Clostridium perfringens phospholipase C].", "content": "The procedure for separation and purification of isoenzymes of phospholipase C from Clostridium perfringens (PLC) was developed. The procedure included primary concentration of culture liquid proteins and isoenzyme separtion on DEAE-cellulose during negative sorption of the major isoenzyme. Further purification of the isoenzymes was achieved by (NH4)2SO4 fractionation by Sephadex gel-filtration and isoelectric focusing. During polyacrylamide gel electrophoresis and precipitation reaction in the agar with the antiperfringens hyperimmune serum alpha1-PLC preparations were homogenous. Their coefficient of sedimentation was 3.8 S and isoelectric point was 5.50. The minor isoenzyme alpha2-PLC had the same coefficient of sedimentation and the isoelectric point of 5.35.", "contents": "[Separation and purification of isoenzymes of Clostridium perfringens phospholipase C]. The procedure for separation and purification of isoenzymes of phospholipase C from Clostridium perfringens (PLC) was developed. The procedure included primary concentration of culture liquid proteins and isoenzyme separtion on DEAE-cellulose during negative sorption of the major isoenzyme. Further purification of the isoenzymes was achieved by (NH4)2SO4 fractionation by Sephadex gel-filtration and isoelectric focusing. During polyacrylamide gel electrophoresis and precipitation reaction in the agar with the antiperfringens hyperimmune serum alpha1-PLC preparations were homogenous. Their coefficient of sedimentation was 3.8 S and isoelectric point was 5.50. The minor isoenzyme alpha2-PLC had the same coefficient of sedimentation and the isoelectric point of 5.35."}
{"id": "PMID:209440", "title": "[Effect of removal and stimulation of the superior cervical sympathetic ganglia on the activity of oxidation-reduction enzymes in the neurosecretory cells of the anterior hypothalamus in rabbits].", "content": "Experiments were conducted on rabbits. A study was made of the activity of the redox enzymes--glucose-6-phosphate dehydrogenase (G-6-PDH), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), NAD-and NADP-diaphorases, cytochromeoxidase (CCO), alpha-glycerophosphate dehydrogenase (alpha-GPDH) in the supraoptic and paraventricular nuclei of the hypothalamus and the posterior lobe of the hypophysis under conditions of stimulation and removal of the superior cervical sympathetic ganglia. There was revealed a correlation between the activity of the tissue respiration enzymes (SDH, MDH, NAD- and NADP-diaphorase, CCO) and the functional condition of the hypothalamo-neurohypophysial neurosecretory system. However, the enzymes of the pentose-phosphate (G-6-PDH) and glycerophosphate shunt (alpha-GPDH) and also of the anaerobic way of oxidation (LDH) reacted nonspecifically on the induced effects.", "contents": "[Effect of removal and stimulation of the superior cervical sympathetic ganglia on the activity of oxidation-reduction enzymes in the neurosecretory cells of the anterior hypothalamus in rabbits]. Experiments were conducted on rabbits. A study was made of the activity of the redox enzymes--glucose-6-phosphate dehydrogenase (G-6-PDH), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), NAD-and NADP-diaphorases, cytochromeoxidase (CCO), alpha-glycerophosphate dehydrogenase (alpha-GPDH) in the supraoptic and paraventricular nuclei of the hypothalamus and the posterior lobe of the hypophysis under conditions of stimulation and removal of the superior cervical sympathetic ganglia. There was revealed a correlation between the activity of the tissue respiration enzymes (SDH, MDH, NAD- and NADP-diaphorase, CCO) and the functional condition of the hypothalamo-neurohypophysial neurosecretory system. However, the enzymes of the pentose-phosphate (G-6-PDH) and glycerophosphate shunt (alpha-GPDH) and also of the anaerobic way of oxidation (LDH) reacted nonspecifically on the induced effects."}
{"id": "PMID:209441", "title": "[Relationship between the hypophyseal-adrenal and the genital systems in silver-black foxes].", "content": "Interaction between the hypophysial-adrenal system (HAS) and the hypophysis-gonad system was studied. For this purpose the foxes were subjected to total gonadectomy 8 months before they were sacrificed. Functional activity of the HAS was judged by the hypophysis ACTH content, corticosteroid production by the adrenal cortex in vitro, and by the glucocorticoid concentration in the peripheral blood. Castration of male foxes foxes failed to influence the activity of various HAS links. Gonadectomy of females was accompanied by changes in the activity of individual HAS links in different direction--some reduction of ACTH in the hypophysis, a sharp and significant fall of the peripheral blood glucocorticoid level and a marked significant elevation of hydrococortisone production in the adrenal cortex in vitro.", "contents": "[Relationship between the hypophyseal-adrenal and the genital systems in silver-black foxes]. Interaction between the hypophysial-adrenal system (HAS) and the hypophysis-gonad system was studied. For this purpose the foxes were subjected to total gonadectomy 8 months before they were sacrificed. Functional activity of the HAS was judged by the hypophysis ACTH content, corticosteroid production by the adrenal cortex in vitro, and by the glucocorticoid concentration in the peripheral blood. Castration of male foxes foxes failed to influence the activity of various HAS links. Gonadectomy of females was accompanied by changes in the activity of individual HAS links in different direction--some reduction of ACTH in the hypophysis, a sharp and significant fall of the peripheral blood glucocorticoid level and a marked significant elevation of hydrococortisone production in the adrenal cortex in vitro."}
{"id": "PMID:209448", "title": "Direct C-1 hydroxylation of vitamin D compounds: convenient preparation of 1alpha-hydroxyvitamin D3, 1alpha, 25-dihydroxyvitamin D3, and 1alpha-hydroxyvitamin D2.", "content": "An efficient procedure for the direct C-1 hydroxylation of vitamin D compounds has been developed. The method involves conversion of vitamin D3 tosylates to 3,5-cyclovitamin D derivatives, allylic oxidation with selenium dioxide, and acid-catalyzed solvolysis to the 1 alpha-hydroxyvitamin D analogs. When applied to vitamin D3,25-hydroxyvitamin D3, and vitamin D2, this sequence give the corresponding 1alpha-hydroxylated derivatives in 10-15% yield.", "contents": "Direct C-1 hydroxylation of vitamin D compounds: convenient preparation of 1alpha-hydroxyvitamin D3, 1alpha, 25-dihydroxyvitamin D3, and 1alpha-hydroxyvitamin D2. An efficient procedure for the direct C-1 hydroxylation of vitamin D compounds has been developed. The method involves conversion of vitamin D3 tosylates to 3,5-cyclovitamin D derivatives, allylic oxidation with selenium dioxide, and acid-catalyzed solvolysis to the 1 alpha-hydroxyvitamin D analogs. When applied to vitamin D3,25-hydroxyvitamin D3, and vitamin D2, this sequence give the corresponding 1alpha-hydroxylated derivatives in 10-15% yield."}
{"id": "PMID:209449", "title": "Regulation of cholesterol biosynthesis in HeLa S3G cells by serum lipoproteins: dexamethasone-mediated interference with suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase.", "content": "Depression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating); EC 1.1.1.34] was elicited by the removal of serum from the growth medium of HeLa S3G cells with a concomitant expected increase in cellular sterol biosynthesis; if dexamethasone (9alpha-fluoro-11beta,17alpha,21-trihydroxy-16alpha-methyl-1, 4-pregnadiene-3,20-dione) was present in the serumless medium, there was an augmentation of HMG-CoA reductase activity but a suppression of sterol biosynthesis. When human serum, human low density lipoprotein, or calf serum was present in the medium, there was a reduction of both the enzyme activity and sterol biosynthesis, but the presence of dexamethasone resulted in an increase in HMG-CoA reductase activity as compared to the controls containing human serum, low density lipoprotein, or calf serum alone. In contrast, either low density lipoprotein or whole serum supplementation eliminated the differences in acetate incorporation into sterols between glucocorticoid-treated and untreated cells. Human high density lipoproteins had little effect on the enzyme activity and abolished the difference in sterol biosynthesis only at relatively high concentrations. Addition of low density lipoproteins to cells after preincubation in serumless medium elicited the same rate of decay of HMG-CoA reductase (t(1/2) 3.8-4.2 hr) regardless of the presence of glucocorticoids in the medium, but there was an exaggerated lag before the onset of suppression in the hormone-treated cells. If free cholesterol was present in the medium, the dexamethasone augmentation of HMG-CoA reductase was maintained, but the addition of either 7-ketocholesterol or 25-hydroxycholesterol abolished the difference between glucocorticoid-treated and control cells. These observations suggest that, under certain physiological conditions, HMG-CoA reductase activity no longer accurately reflects cellular sterol biosynthesis.", "contents": "Regulation of cholesterol biosynthesis in HeLa S3G cells by serum lipoproteins: dexamethasone-mediated interference with suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Depression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating); EC 1.1.1.34] was elicited by the removal of serum from the growth medium of HeLa S3G cells with a concomitant expected increase in cellular sterol biosynthesis; if dexamethasone (9alpha-fluoro-11beta,17alpha,21-trihydroxy-16alpha-methyl-1, 4-pregnadiene-3,20-dione) was present in the serumless medium, there was an augmentation of HMG-CoA reductase activity but a suppression of sterol biosynthesis. When human serum, human low density lipoprotein, or calf serum was present in the medium, there was a reduction of both the enzyme activity and sterol biosynthesis, but the presence of dexamethasone resulted in an increase in HMG-CoA reductase activity as compared to the controls containing human serum, low density lipoprotein, or calf serum alone. In contrast, either low density lipoprotein or whole serum supplementation eliminated the differences in acetate incorporation into sterols between glucocorticoid-treated and untreated cells. Human high density lipoproteins had little effect on the enzyme activity and abolished the difference in sterol biosynthesis only at relatively high concentrations. Addition of low density lipoproteins to cells after preincubation in serumless medium elicited the same rate of decay of HMG-CoA reductase (t(1/2) 3.8-4.2 hr) regardless of the presence of glucocorticoids in the medium, but there was an exaggerated lag before the onset of suppression in the hormone-treated cells. If free cholesterol was present in the medium, the dexamethasone augmentation of HMG-CoA reductase was maintained, but the addition of either 7-ketocholesterol or 25-hydroxycholesterol abolished the difference between glucocorticoid-treated and control cells. These observations suggest that, under certain physiological conditions, HMG-CoA reductase activity no longer accurately reflects cellular sterol biosynthesis."}
{"id": "PMID:209450", "title": "Mapping of linear and circular forms of mouse mammary tumor virus DNA with restriction endonucleases: evidence for a large specific deletion occurring at high frequency during circularization.", "content": "Rat hepatoma cells infected with mouse mammary tumor virus contain multiple forms of unintegrated viral DNA when grown in the presence of glucocorticoids. Using the DNA transfer procedure of Southern, we have prepared restriction endonuclease fragment maps of these forms of viral DNA. The maps indicate that: (i) the major species of viral DNA is a linear molecule of 5.9 X 10(6) Mr located in the cytoplasm; (ii) the nuclei contain covalently closed circular viral DNA of two distinct sizes (5.1 X 10(6) and 5.9 X 10(6) Mr) in addition to linear molecules (5.9 X 10(6) Mr); (iii) the linear molecule has specific termini; (iv) there is extensive homology between regions at or near termini of the linear molecule; (v) the predominant form of circular DNA lacks 1.2 kilobase pairs present in both the larger circular molecule and the linear molecule; and (vi) the sequences deleted from the majority of the circular DNA molecules are located at the ends of the linear DNA that are joined during circularization.", "contents": "Mapping of linear and circular forms of mouse mammary tumor virus DNA with restriction endonucleases: evidence for a large specific deletion occurring at high frequency during circularization. Rat hepatoma cells infected with mouse mammary tumor virus contain multiple forms of unintegrated viral DNA when grown in the presence of glucocorticoids. Using the DNA transfer procedure of Southern, we have prepared restriction endonuclease fragment maps of these forms of viral DNA. The maps indicate that: (i) the major species of viral DNA is a linear molecule of 5.9 X 10(6) Mr located in the cytoplasm; (ii) the nuclei contain covalently closed circular viral DNA of two distinct sizes (5.1 X 10(6) and 5.9 X 10(6) Mr) in addition to linear molecules (5.9 X 10(6) Mr); (iii) the linear molecule has specific termini; (iv) there is extensive homology between regions at or near termini of the linear molecule; (v) the predominant form of circular DNA lacks 1.2 kilobase pairs present in both the larger circular molecule and the linear molecule; and (vi) the sequences deleted from the majority of the circular DNA molecules are located at the ends of the linear DNA that are joined during circularization."}
{"id": "PMID:209451", "title": "Transduction of a bacterial gene into mammalian cells.", "content": "The transduction of an Escherichia coli gene into mammalian cells is described. A supressor tRNA gene was linked to a simian virus 40 (SV40) vector in vitro and the recombinant was used to transfect rat embryo cells and monkey kidney cells. The hybrid SV40 genome, SV40-su+ III, retained genetic information required for autonomous replication and cellular transformation and had a 1300-base-pair DNA segment in the late gene region (between the restriction endonuclease sits Hpa II at 0.735 and EcoRI at 0/1.0 on the SV40 genetic map) replaced by an 870-base-pair bacterial DNA segment containing the suppressor tRNA gene, su+ III (tRNATyrsu+III). The structure and fate of the SV40-su+III chimera were determined by DNA reassociation kinetic analysis and restriction enzyme cleavage of the total cellular DNA from transformed rat embryo cells and persistently infected monkey cells. Hybridization with radiolabeled probes specific for vector (SV40) or su+III DNA sequences revealed primarily nonintegrated or free hybrid genomes. In cloned lines of both cell types, the bacterial DNA segment was recovered intact, as judged by the length of the segment excised by restriction endonucleases and its ability to hybridize to the radiolabeled bacterial DNA probe and not to the SV40 probe.", "contents": "Transduction of a bacterial gene into mammalian cells. The transduction of an Escherichia coli gene into mammalian cells is described. A supressor tRNA gene was linked to a simian virus 40 (SV40) vector in vitro and the recombinant was used to transfect rat embryo cells and monkey kidney cells. The hybrid SV40 genome, SV40-su+ III, retained genetic information required for autonomous replication and cellular transformation and had a 1300-base-pair DNA segment in the late gene region (between the restriction endonuclease sits Hpa II at 0.735 and EcoRI at 0/1.0 on the SV40 genetic map) replaced by an 870-base-pair bacterial DNA segment containing the suppressor tRNA gene, su+ III (tRNATyrsu+III). The structure and fate of the SV40-su+III chimera were determined by DNA reassociation kinetic analysis and restriction enzyme cleavage of the total cellular DNA from transformed rat embryo cells and persistently infected monkey cells. Hybridization with radiolabeled probes specific for vector (SV40) or su+III DNA sequences revealed primarily nonintegrated or free hybrid genomes. In cloned lines of both cell types, the bacterial DNA segment was recovered intact, as judged by the length of the segment excised by restriction endonucleases and its ability to hybridize to the radiolabeled bacterial DNA probe and not to the SV40 probe."}
{"id": "PMID:209452", "title": "Fluorescent labeling of hormone receptors in viable cells: preparation and properties of highly fluorescent derivatives of epidermal growth factor and insulin.", "content": "Highly fluorescent analogs of insulin and epidermal growth factor were prepared by the covalent attachment of these peptides to alpha-lactalbumin molecules that were highly substituted (i.e., seven to one) with rhodamine molecules. The alpha-lactalbumin was specifically linked to the lysine residue of insulin or to the alpha-amino group of epidermal growth factor. The insulin derivative retained 1.15% of its potency in stimulating glucose oxidation in fat cells but retained about 8.3% of its binding affinity toward receptors. The epidermal growth factor derivative was completely active in binding to fibroblast receptors and 40% as potent as the native hormone in stimulating DNA synthesis. These highly fluorescent derivatives were suitable for the specific visual labeling of receptor sites in viable cells and for measuring the lateral mobilities of the receptor-hormone complexes by fluorescent photobleaching recovery techniques. By these methods it was shown that the hormone-receptor complexes can move laterally in the plane of the plasma membrane with a diffusion coefficient of (3-5) X 10(-10) cm2/sec.", "contents": "Fluorescent labeling of hormone receptors in viable cells: preparation and properties of highly fluorescent derivatives of epidermal growth factor and insulin. Highly fluorescent analogs of insulin and epidermal growth factor were prepared by the covalent attachment of these peptides to alpha-lactalbumin molecules that were highly substituted (i.e., seven to one) with rhodamine molecules. The alpha-lactalbumin was specifically linked to the lysine residue of insulin or to the alpha-amino group of epidermal growth factor. The insulin derivative retained 1.15% of its potency in stimulating glucose oxidation in fat cells but retained about 8.3% of its binding affinity toward receptors. The epidermal growth factor derivative was completely active in binding to fibroblast receptors and 40% as potent as the native hormone in stimulating DNA synthesis. These highly fluorescent derivatives were suitable for the specific visual labeling of receptor sites in viable cells and for measuring the lateral mobilities of the receptor-hormone complexes by fluorescent photobleaching recovery techniques. By these methods it was shown that the hormone-receptor complexes can move laterally in the plane of the plasma membrane with a diffusion coefficient of (3-5) X 10(-10) cm2/sec."}
{"id": "PMID:209453", "title": "Prolyl hydroxylase half reaction: peptidyl prolyl-independent decarboxylation of alpha-ketoglutarate.", "content": "Prolyl hydroxylase (proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) is a mixed-function oxygenase that hydroxylates peptidyl proline with the simultaneous and stoichiometric decarboxylation of alpha-ketoglutarate to succinate and CO2. It has been found that highly purified preparations of the enzyme can decarboxylate alpha-ketoglutarate in the absence of a peptidyl proline substrate. The uncoupled decarboxylation proceeds at only a fraction of the rate of the whole reaction and for study requires substrate quantities of the pure enzyme, as well as oxygen, ferrous ion, and ascorbate. No hydroxyproline is formed under these conditions. Immobilized antiserum to prolyl hydroxylase was found to remove both activities from enzyme preparations. However, addition of free antiserum during incubation inhibits only the complete reaction. Poly(L-proline), a specific inhibitor of prolyl hydroxylation, enhances the uncoupled decarboxylation of alpha-ketoglutarate without itself being hydroxylated. All of these findings prove that alpha-ketoglutarate can serve as substrate in the absence of peptidyl proline and is most likely the initial site of attack by oxygen. In the coupled reaction an oxidized form of the keto acid, perhaps a peroxy acid, then attacks prolyl residues in the unhydroxylated substrate.", "contents": "Prolyl hydroxylase half reaction: peptidyl prolyl-independent decarboxylation of alpha-ketoglutarate. Prolyl hydroxylase (proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) is a mixed-function oxygenase that hydroxylates peptidyl proline with the simultaneous and stoichiometric decarboxylation of alpha-ketoglutarate to succinate and CO2. It has been found that highly purified preparations of the enzyme can decarboxylate alpha-ketoglutarate in the absence of a peptidyl proline substrate. The uncoupled decarboxylation proceeds at only a fraction of the rate of the whole reaction and for study requires substrate quantities of the pure enzyme, as well as oxygen, ferrous ion, and ascorbate. No hydroxyproline is formed under these conditions. Immobilized antiserum to prolyl hydroxylase was found to remove both activities from enzyme preparations. However, addition of free antiserum during incubation inhibits only the complete reaction. Poly(L-proline), a specific inhibitor of prolyl hydroxylation, enhances the uncoupled decarboxylation of alpha-ketoglutarate without itself being hydroxylated. All of these findings prove that alpha-ketoglutarate can serve as substrate in the absence of peptidyl proline and is most likely the initial site of attack by oxygen. In the coupled reaction an oxidized form of the keto acid, perhaps a peroxy acid, then attacks prolyl residues in the unhydroxylated substrate."}
{"id": "PMID:209454", "title": "BK virus DNA: cleavage map and sequence analysis.", "content": "A detailed physical map of the BK virus (MM strain) genome has been constructed with respect to the cleavage sites of 11 different restriction enzymes. The enzymes cut BKV(MM) DNA at 61 specific sites whose locations have been determined. Preliminary nucleotide sequence was carried out in the region from 0.70-0.75 map positions on BKV(MM) DNA. An 80% homology was found at 0.714-0.744 map positions on BKV(MM) DNA with 0.722-0.752 map positions on simian virus 40 DNA. This region of simian virus 40 DNA codes for the synthesis of the leader sequence of late mRNA.", "contents": "BK virus DNA: cleavage map and sequence analysis. A detailed physical map of the BK virus (MM strain) genome has been constructed with respect to the cleavage sites of 11 different restriction enzymes. The enzymes cut BKV(MM) DNA at 61 specific sites whose locations have been determined. Preliminary nucleotide sequence was carried out in the region from 0.70-0.75 map positions on BKV(MM) DNA. An 80% homology was found at 0.714-0.744 map positions on BKV(MM) DNA with 0.722-0.752 map positions on simian virus 40 DNA. This region of simian virus 40 DNA codes for the synthesis of the leader sequence of late mRNA."}
{"id": "PMID:209455", "title": "Nucleotide sequence of the simian virus 40 small-t gene.", "content": "The nucleotide sequence of the segment of simian virus 40 DNA between standard map positions 0.53 and 0.65, i.e., approximately half of the restriction fragment Hind A, is reported. This segment is located near the beginning of the early region and is transcribed counterclockwise. There is a potential initiating ATG signal at 13 nucleotides from the Hind C-Hind A junction in the strand with the same polarity as the early mRNA. From this signal on, an open reading frame is present which would allow the synthesis of a polypeptide of 174 amino acids until a TAA termination codon is reached at nucleotide 602 (map position 0.547). This polypeptide, revealed by the DNA sequence, corresponds almost certainly to small-t antigen. Correlation of the deduced amino acid sequence with the NH(2)-terminal sequences of small-t and large-T (tumor) antigens of simian virus 40, as established by Paucha et al. [Paucha, E., Mellor, A., Harvey, R., Smith, A. E., Hewick, R. M. & Waterfield, M. D. (1978) [Proc. Natl. Acad. Sci. USA 75, 2165-2169], strongly argues that both proteins are indeed initiated at the ATG triplet. Because the DNA region between 0.547 and 0.534 is blocked for translation in all three reading frames by multiple termination condons, we conclude that the large-T antigen must be coded for by two noncontiguous DNA segments: the segment from 0.65 to around 0.60, which small-t and large-T antigens share, and another segment starting at some point after position 0.534 and continuing counterclockwise until it terminates at map position 0.174. Small-t antigen is methionine-rich and has a remarkably high number of cysteine residues clustered mainly in its COOH-terminal half. It is rich in both basic and acidic residues, the former being slightly in excess.", "contents": "Nucleotide sequence of the simian virus 40 small-t gene. The nucleotide sequence of the segment of simian virus 40 DNA between standard map positions 0.53 and 0.65, i.e., approximately half of the restriction fragment Hind A, is reported. This segment is located near the beginning of the early region and is transcribed counterclockwise. There is a potential initiating ATG signal at 13 nucleotides from the Hind C-Hind A junction in the strand with the same polarity as the early mRNA. From this signal on, an open reading frame is present which would allow the synthesis of a polypeptide of 174 amino acids until a TAA termination codon is reached at nucleotide 602 (map position 0.547). This polypeptide, revealed by the DNA sequence, corresponds almost certainly to small-t antigen. Correlation of the deduced amino acid sequence with the NH(2)-terminal sequences of small-t and large-T (tumor) antigens of simian virus 40, as established by Paucha et al. [Paucha, E., Mellor, A., Harvey, R., Smith, A. E., Hewick, R. M. & Waterfield, M. D. (1978) [Proc. Natl. Acad. Sci. USA 75, 2165-2169], strongly argues that both proteins are indeed initiated at the ATG triplet. Because the DNA region between 0.547 and 0.534 is blocked for translation in all three reading frames by multiple termination condons, we conclude that the large-T antigen must be coded for by two noncontiguous DNA segments: the segment from 0.65 to around 0.60, which small-t and large-T antigens share, and another segment starting at some point after position 0.534 and continuing counterclockwise until it terminates at map position 0.174. Small-t antigen is methionine-rich and has a remarkably high number of cysteine residues clustered mainly in its COOH-terminal half. It is rich in both basic and acidic residues, the former being slightly in excess."}
{"id": "PMID:209456", "title": "Large and small tumor antigens from simian virus 40 have identical amino termini mapping at 0.65 map units.", "content": "Large and small tumor (T)antigens of simian virus 40 were synthesized in vitro with L-cell extracts that had been treated by the method of Palmiter to prevent amino-terminal acetylation of nascent proteins. Partial amino-terminal amino acid sequences of both forms of T-antigen were determined and found to be identical. Methionine residues were located at positions 1 and 14, a lysine residue at position 3, and leucine residues at positions 5, 11, 13,16, 17, and 19. These amino acid sequence data match perfectly the amino acid sequence predicted from a sequence of nucleotides in the E strand of simian virus 40 DNA which begins near the junction between HindII/III fragments A and C at about 0.65 map units. This strongly suggests that the sequence coding for the amino terminus of both proteins is located at this position. Furthermore, the data are consistent with a model for the synthesis of both forms of T-antigen that predicts that (i) small T-antigen is coded for by a sequence of nucleotides from the 5' end of the early region and (ii) large T-antigen is coded for by nucleotide sequences from two noncontiguous regions of simian virus 40 DNA.", "contents": "Large and small tumor antigens from simian virus 40 have identical amino termini mapping at 0.65 map units. Large and small tumor (T)antigens of simian virus 40 were synthesized in vitro with L-cell extracts that had been treated by the method of Palmiter to prevent amino-terminal acetylation of nascent proteins. Partial amino-terminal amino acid sequences of both forms of T-antigen were determined and found to be identical. Methionine residues were located at positions 1 and 14, a lysine residue at position 3, and leucine residues at positions 5, 11, 13,16, 17, and 19. These amino acid sequence data match perfectly the amino acid sequence predicted from a sequence of nucleotides in the E strand of simian virus 40 DNA which begins near the junction between HindII/III fragments A and C at about 0.65 map units. This strongly suggests that the sequence coding for the amino terminus of both proteins is located at this position. Furthermore, the data are consistent with a model for the synthesis of both forms of T-antigen that predicts that (i) small T-antigen is coded for by a sequence of nucleotides from the 5' end of the early region and (ii) large T-antigen is coded for by nucleotide sequences from two noncontiguous regions of simian virus 40 DNA."}
{"id": "PMID:209457", "title": "Local mutagenesis: a method for generating viral mutants with base substitutions in preselected regions of the viral genome.", "content": "DNA from simian virus 40 (SV40) was prepared for local mutagenesis by nicking the molecule at a specific site with a restriction endonuclease that recognizes one site in SV40 DNA and then extending the nick enzymatically to expose a short, single-stranded segment of DNA. The \"gapped\" DNA was treated with a single-strand-specific mutagen, sodium bisulfite, which converts cytosine to uracil. After mutagenesis, the gap was repaired with DNA polymerase, generating molecules resistant to the restriction enzyme used to make the initial nick. From cells infected with DNA thus modified, SV40 mutants were isolated that had enzyme-resistant genomes. In some cases, precise positions of G.C to A.T transitions could be inferred from the patterns of susceptibility of mutant DNA to other restriction endonucleases whose recognition sequences were altered by the mutagenesis procedure. One of the restriction endonuclease sites mutagenized (Bgl I) maps at the origin of SV40 DNA replication and near sequences corresponding to the 5' ends of viral mRNAs. Many of the resulting Bgl I-resistant mutants yielded small plaques, suggesting partial defectiveness in DNA replication or transcription.", "contents": "Local mutagenesis: a method for generating viral mutants with base substitutions in preselected regions of the viral genome. DNA from simian virus 40 (SV40) was prepared for local mutagenesis by nicking the molecule at a specific site with a restriction endonuclease that recognizes one site in SV40 DNA and then extending the nick enzymatically to expose a short, single-stranded segment of DNA. The \"gapped\" DNA was treated with a single-strand-specific mutagen, sodium bisulfite, which converts cytosine to uracil. After mutagenesis, the gap was repaired with DNA polymerase, generating molecules resistant to the restriction enzyme used to make the initial nick. From cells infected with DNA thus modified, SV40 mutants were isolated that had enzyme-resistant genomes. In some cases, precise positions of G.C to A.T transitions could be inferred from the patterns of susceptibility of mutant DNA to other restriction endonucleases whose recognition sequences were altered by the mutagenesis procedure. One of the restriction endonuclease sites mutagenized (Bgl I) maps at the origin of SV40 DNA replication and near sequences corresponding to the 5' ends of viral mRNAs. Many of the resulting Bgl I-resistant mutants yielded small plaques, suggesting partial defectiveness in DNA replication or transcription."}
{"id": "PMID:209458", "title": "Binding and kinetic data for rabbit liver fructose-1,6-bisphosphatase with Zn2+ as cofactor.", "content": "Atomic absorption determinations of zinc content were employed to demonstrate the technique to obtain zinc-free rabbit liver fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11). Reactivation of the apoenzyme by Zn(2+) is rapid (within 1 min) and restores up to 96% of the initial specific activity. Gel filtration measurements showed that the enzyme contains four binding sites for zinc per molecule, one per subunit. The dissociation constants for the initial two binding sites are less than 0.1 muM. In the presence of a substrate analog, (alpha + beta) methyl D-fructofuranoside 1,6-bisphosphate, at a level where two analog molecules are bound per phosphatase molecule, a total of eight Zn(2+) ions bind at 8 muM Zn(2+), revealing the presence of additional binding sites, including the catalytic one. The activity in the presence of Zn(2+) is maximal at ca. 8 muM Zn(2+), which corresponds to saturation of the four subunit sites plus the catalytic sites in the presence of substrate. At metal ion concentrations less than 10 muM, the order of activation is Zn(2+) > Mn(2+) > Mg(2+). In kinetic assays with two metal cofactors the effect of Zn(2+) at concentrations less than 10 muM on either the Mg(2+) or the Mn(2+) assays is inhibitory owing to the apparent formation of mixed (two different elements) metal ion-enzyme complexes possessing a catalytic activity that is measureable but lower than anticipated if the catalysis by the various metal ions is simply additive. Hence the activation by EDTA of the Mg(2+) and Mn(2+) assays is explicable in terms of Zn(2+) removal, thus eliminating mixed metal species. Collectively these observations suggest that fructose-1,6-bisphosphatase may function in vivo as a Zn(2+) metalloprotein.", "contents": "Binding and kinetic data for rabbit liver fructose-1,6-bisphosphatase with Zn2+ as cofactor. Atomic absorption determinations of zinc content were employed to demonstrate the technique to obtain zinc-free rabbit liver fructose-1,6-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11). Reactivation of the apoenzyme by Zn(2+) is rapid (within 1 min) and restores up to 96% of the initial specific activity. Gel filtration measurements showed that the enzyme contains four binding sites for zinc per molecule, one per subunit. The dissociation constants for the initial two binding sites are less than 0.1 muM. In the presence of a substrate analog, (alpha + beta) methyl D-fructofuranoside 1,6-bisphosphate, at a level where two analog molecules are bound per phosphatase molecule, a total of eight Zn(2+) ions bind at 8 muM Zn(2+), revealing the presence of additional binding sites, including the catalytic one. The activity in the presence of Zn(2+) is maximal at ca. 8 muM Zn(2+), which corresponds to saturation of the four subunit sites plus the catalytic sites in the presence of substrate. At metal ion concentrations less than 10 muM, the order of activation is Zn(2+) > Mn(2+) > Mg(2+). In kinetic assays with two metal cofactors the effect of Zn(2+) at concentrations less than 10 muM on either the Mg(2+) or the Mn(2+) assays is inhibitory owing to the apparent formation of mixed (two different elements) metal ion-enzyme complexes possessing a catalytic activity that is measureable but lower than anticipated if the catalysis by the various metal ions is simply additive. Hence the activation by EDTA of the Mg(2+) and Mn(2+) assays is explicable in terms of Zn(2+) removal, thus eliminating mixed metal species. Collectively these observations suggest that fructose-1,6-bisphosphatase may function in vivo as a Zn(2+) metalloprotein."}
{"id": "PMID:209459", "title": "Adenosine 5'-O-([gamma-18O]gamma-thio)triphosphate chiral at the gamma-phosphorus: stereochemical consequences of reactions catalyzed by pyruvate kinase, glycerol kinase, and hexokinase.", "content": "The 2-[18O]phosphorothioate of D-glycerate, chiral at phosphorus, was prepared. The chiral phosphoryl group was transferred enzymically to ADP [by using enolase and pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase; EC 2.7.1.40)] resulting in the synthesis of adenosine 5'-O-([gamma-18O],gamma-thio)triphosphate. This labeled ATP was used as a thiophosphoryl group donor in the reactions catalyzed by glycerol kinase (ATP:glycerol 3-phosphotransferase; EC 2.7.1.30) and by hexokinase (ATP:D-hexose 6-phosphotransferase; EC 2.7.1.1). The product from the latter (glucose 6-phosphorothioate) was converted enzymically into glycerol phosphorothioate. Determination of the relative configurations and diastereoisomeric purities of the samples of glycerol phosphorothioate demonstrates that all three phosphokinases (pyruvate kinase, glycerol kinase, and hexokinase) transfer the thiophosphoryl group with complete stereospecificity, and further shows that these reactions follow an identical stereochemical course.", "contents": "Adenosine 5'-O-([gamma-18O]gamma-thio)triphosphate chiral at the gamma-phosphorus: stereochemical consequences of reactions catalyzed by pyruvate kinase, glycerol kinase, and hexokinase. The 2-[18O]phosphorothioate of D-glycerate, chiral at phosphorus, was prepared. The chiral phosphoryl group was transferred enzymically to ADP [by using enolase and pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase; EC 2.7.1.40)] resulting in the synthesis of adenosine 5'-O-([gamma-18O],gamma-thio)triphosphate. This labeled ATP was used as a thiophosphoryl group donor in the reactions catalyzed by glycerol kinase (ATP:glycerol 3-phosphotransferase; EC 2.7.1.30) and by hexokinase (ATP:D-hexose 6-phosphotransferase; EC 2.7.1.1). The product from the latter (glucose 6-phosphorothioate) was converted enzymically into glycerol phosphorothioate. Determination of the relative configurations and diastereoisomeric purities of the samples of glycerol phosphorothioate demonstrates that all three phosphokinases (pyruvate kinase, glycerol kinase, and hexokinase) transfer the thiophosphoryl group with complete stereospecificity, and further shows that these reactions follow an identical stereochemical course."}
{"id": "PMID:209460", "title": "Recognition site of Escherichia coli B restriction enzyme on phi XsB1 and simian virus 40 DNAs: an interrupted sequence.", "content": "Methyl groups placed on varphiXsB1 replicative form DNA by the Escherichia coli B modification enzyme are located in the overlap between fragments Mbo II-3 and Alu I-2, a 61-base-pair DNA segment. Mutations that led to loss of susceptibility to restriction by E. coli B occurred within this segment at three positions spanning 14 nucleotides. A sequence difference between varphiXsB1 and varphiXam3cs70, a varphiX174 strain not restricted by E. coli B, occurs at one of these positions. The site on simian virus 40 DNA methylated by the modification enzyme is located in the 115-base-pair overlap between fragments Hae III-I and Alu I-G. The sequences of these segments of varphiXsB1 and simian virus 40 DNA and two regions of phage f1 DNA recognized by the E. coli B restriction enzyme [Ravetch, J. V., Horiuchi, K. & Zinder, N. D. (1978) Proc. Natl. Acad. Sci. USA 75, 2266-2270] contain a homology of nine bases in the configuration:5'-T-G-A... 8N... T-G-C-T... 9N... T-N-N-T-3'. The sequence 5'-T-G-A... 8N... T-G-C-T-3' may constitute the restriction enzyme recognition site since it does not occur in varphiXam3cs70 DNA and occurs only once in simian virus 40 DNA, and since all observed mutations leading to loss of the site occur at one of the bases specified by this sequence. Analysis of the sequence of varphiXam3cs70 showed that if no other residues are recognized, all seven of these bases are essential for recognition and the interval between the two groups of specified bases must be precisely eight.", "contents": "Recognition site of Escherichia coli B restriction enzyme on phi XsB1 and simian virus 40 DNAs: an interrupted sequence. Methyl groups placed on varphiXsB1 replicative form DNA by the Escherichia coli B modification enzyme are located in the overlap between fragments Mbo II-3 and Alu I-2, a 61-base-pair DNA segment. Mutations that led to loss of susceptibility to restriction by E. coli B occurred within this segment at three positions spanning 14 nucleotides. A sequence difference between varphiXsB1 and varphiXam3cs70, a varphiX174 strain not restricted by E. coli B, occurs at one of these positions. The site on simian virus 40 DNA methylated by the modification enzyme is located in the 115-base-pair overlap between fragments Hae III-I and Alu I-G. The sequences of these segments of varphiXsB1 and simian virus 40 DNA and two regions of phage f1 DNA recognized by the E. coli B restriction enzyme [Ravetch, J. V., Horiuchi, K. & Zinder, N. D. (1978) Proc. Natl. Acad. Sci. USA 75, 2266-2270] contain a homology of nine bases in the configuration:5'-T-G-A... 8N... T-G-C-T... 9N... T-N-N-T-3'. The sequence 5'-T-G-A... 8N... T-G-C-T-3' may constitute the restriction enzyme recognition site since it does not occur in varphiXam3cs70 DNA and occurs only once in simian virus 40 DNA, and since all observed mutations leading to loss of the site occur at one of the bases specified by this sequence. Analysis of the sequence of varphiXam3cs70 showed that if no other residues are recognized, all seven of these bases are essential for recognition and the interval between the two groups of specified bases must be precisely eight."}
{"id": "PMID:209461", "title": "Identification of the Mtv-2 gene responsible for the early appearance of mammary tumors in the GR mouse by nucleic acid hybridization.", "content": "In the mouse strain GR, the Mtv-2 gene controls the expression of large amounts of mammary tumor virus (MTV) antigens in the milk at first lactation. It also controls the early appearance of mammary tumors. We have investigated the number of MTV proviral sequences associated with this Mtv-2 gene by nucleic acid hybridization between MTV [(3)H]cDNA and DNA from GR, B10, and GR-Mtv-2(-) mice. B10 and GR-Mtv-2(-) mice lack Mtv-2 gene expression. The molecular hybridizations revealed that the DNA of GR mice contains 12 copies of MTV proviral sequences, whereas only 4 copies are present in the DNA of B10 and GR-Mtv-2(-) mice. We therefore conclude that the Mtv-2 gene in the GR mouse strain is associated with eight additional MTV proviral sequences. The four Mtv proviral sequences in the GR-Mtv-2(-) DNA might represent another Mtv gene in the GR mouse. Different amounts of MTV RNA are detected in mammary glands at first lactation of B10 and GR-Mtv-2(-) mice, even though both contain four copies of MTV proviral sequences. This indicates a difference between these two mouse strains either in the regulation of expression of these MTV proviral sequences or in the location of these sequences in the murine genome.", "contents": "Identification of the Mtv-2 gene responsible for the early appearance of mammary tumors in the GR mouse by nucleic acid hybridization. In the mouse strain GR, the Mtv-2 gene controls the expression of large amounts of mammary tumor virus (MTV) antigens in the milk at first lactation. It also controls the early appearance of mammary tumors. We have investigated the number of MTV proviral sequences associated with this Mtv-2 gene by nucleic acid hybridization between MTV [(3)H]cDNA and DNA from GR, B10, and GR-Mtv-2(-) mice. B10 and GR-Mtv-2(-) mice lack Mtv-2 gene expression. The molecular hybridizations revealed that the DNA of GR mice contains 12 copies of MTV proviral sequences, whereas only 4 copies are present in the DNA of B10 and GR-Mtv-2(-) mice. We therefore conclude that the Mtv-2 gene in the GR mouse strain is associated with eight additional MTV proviral sequences. The four Mtv proviral sequences in the GR-Mtv-2(-) DNA might represent another Mtv gene in the GR mouse. Different amounts of MTV RNA are detected in mammary glands at first lactation of B10 and GR-Mtv-2(-) mice, even though both contain four copies of MTV proviral sequences. This indicates a difference between these two mouse strains either in the regulation of expression of these MTV proviral sequences or in the location of these sequences in the murine genome."}
{"id": "PMID:209462", "title": "Ultraviolet reactivation of herpes simplex virus is mutagenic and inducible in mammlian cells.", "content": "The survival of UV-irradiated herpes simplex virus on UV-irradiated Vero cells was increased over that on unirradiated cells. A time period between irradiation of the host cells and infection with virus was needed to achieve maximum reactivation. In parallel experiments in which the frequencies of occurrence of the forward mutation in the thymidine kinase gene of the virus were measured, growth of herpes simplex virus on UV-irradiated cells yielded progeny virus that had higher frequencies of TK- mutants than did progeny from infections of control cells. The time course of development of this mutagenic effect was the same as that for the development of the UV-reactivation capacity. Furthermore, development of the UV reactivation could be blocked by inhibition of protein synthesis. These results suggest that an \"error prone\" inducible UV-reactivation phenomenon exists in mammalian cells.", "contents": "Ultraviolet reactivation of herpes simplex virus is mutagenic and inducible in mammlian cells. The survival of UV-irradiated herpes simplex virus on UV-irradiated Vero cells was increased over that on unirradiated cells. A time period between irradiation of the host cells and infection with virus was needed to achieve maximum reactivation. In parallel experiments in which the frequencies of occurrence of the forward mutation in the thymidine kinase gene of the virus were measured, growth of herpes simplex virus on UV-irradiated cells yielded progeny virus that had higher frequencies of TK- mutants than did progeny from infections of control cells. The time course of development of this mutagenic effect was the same as that for the development of the UV-reactivation capacity. Furthermore, development of the UV reactivation could be blocked by inhibition of protein synthesis. These results suggest that an \"error prone\" inducible UV-reactivation phenomenon exists in mammalian cells."}
{"id": "PMID:209463", "title": "Homologous genes for enolase, phosphogluconate dehydrogenase, phosphoglucomutase, and adenylate kinase are syntenic on mouse chromosome 4 and human chromosome 1p.", "content": "It is possible to generate interspecific somatic cell hybrids that preferentially segregate mouse chromosomes, thus making possible mapping of mouse genes. Therefore, comparison of the linkage relationships of homologous genes in man and mouse is now possible. Chinese hamster x mouse somatic cell hybrids segregating mouse chromosomes were tested for the expression of mouse enolase (ENO-1; EC 4.2.1.11, McKusick no. 17245), 6-phosphogluconate dehydrogenase [PGD; EC 1.1.1.44, McKusick no. 17220], phosphoglucomutase-2 (PGM-2; EC 2.7.5.1, McKusick no. 17190), and adenylate kinase-2 (AK-2; EC 2.7.4.3, McKusick no. 10302). In man, genes coding for the homologous forms of these enzymes have been assigned to the short arm of human chromosome 1. Analysis of 41 primary, independent, hybrid clones indicated that, in the mouse, ENO-1 and AK-2 are syntenic with PGD and PGM-2 and therefore can be assigned to mouse chromosome 4. In contrast, they were asyntenic with 21 other enzymes including mouse dipeptidase-1 (DIP-1, human PEP-C; EC 3.4.11.(*), McKusick no. 17000) assigned to human chromosome arm 1q and mouse chromosome 1. Karyologic analysis confirmed this assignment. These data demonstrate that a large autosomal region (21 map units in the mouse and 51 map units in the human male) has been conserved in the evolution of mouse chromosome 4 and the short arm of human chromosome 1. Identification of such conserved regions will contribute to our understanding of the evolution of the mammalian genome and could suggest gene location by homology mapping.", "contents": "Homologous genes for enolase, phosphogluconate dehydrogenase, phosphoglucomutase, and adenylate kinase are syntenic on mouse chromosome 4 and human chromosome 1p. It is possible to generate interspecific somatic cell hybrids that preferentially segregate mouse chromosomes, thus making possible mapping of mouse genes. Therefore, comparison of the linkage relationships of homologous genes in man and mouse is now possible. Chinese hamster x mouse somatic cell hybrids segregating mouse chromosomes were tested for the expression of mouse enolase (ENO-1; EC 4.2.1.11, McKusick no. 17245), 6-phosphogluconate dehydrogenase [PGD; EC 1.1.1.44, McKusick no. 17220], phosphoglucomutase-2 (PGM-2; EC 2.7.5.1, McKusick no. 17190), and adenylate kinase-2 (AK-2; EC 2.7.4.3, McKusick no. 10302). In man, genes coding for the homologous forms of these enzymes have been assigned to the short arm of human chromosome 1. Analysis of 41 primary, independent, hybrid clones indicated that, in the mouse, ENO-1 and AK-2 are syntenic with PGD and PGM-2 and therefore can be assigned to mouse chromosome 4. In contrast, they were asyntenic with 21 other enzymes including mouse dipeptidase-1 (DIP-1, human PEP-C; EC 3.4.11.(*), McKusick no. 17000) assigned to human chromosome arm 1q and mouse chromosome 1. Karyologic analysis confirmed this assignment. These data demonstrate that a large autosomal region (21 map units in the mouse and 51 map units in the human male) has been conserved in the evolution of mouse chromosome 4 and the short arm of human chromosome 1. Identification of such conserved regions will contribute to our understanding of the evolution of the mammalian genome and could suggest gene location by homology mapping."}
{"id": "PMID:209464", "title": "Restricted classes of immunoglobulin produced by a lymphoid cell line from a patient with agammaglobulinemia.", "content": "Restricted expression of immunoglobulin by a long-term B lymphoid cell line derived from a patient with X-linked agammaglobulinemia is reproted. The patient had peripheral blood B lymphocytes with surface IgD and IgM. Culture of the B cells in vitro with mitogens did not stimulate immunoglobulin secretion, although pokeweed mitogen stimulation resulted in the development of cytoplasmic IgD and IgM. The lymphoid cell line established from these B lymphocytes primarily bore surface IgD, with a small population of cells also bearing surface IgM. These cells also had cytoplasmic immunoglobulin, primarily IgD. The cell line did not have a cytoplasmic pool of immunoglobulin for export and did not secrete immunoglobulin. This B lymphoid cell line is an in vitro analogue of the arrest in differentiation of the patient's B lymphocytes. The IgD-bearing phenotype may represent a normal transitional stage in the differentiation of B lymphocytes.", "contents": "Restricted classes of immunoglobulin produced by a lymphoid cell line from a patient with agammaglobulinemia. Restricted expression of immunoglobulin by a long-term B lymphoid cell line derived from a patient with X-linked agammaglobulinemia is reproted. The patient had peripheral blood B lymphocytes with surface IgD and IgM. Culture of the B cells in vitro with mitogens did not stimulate immunoglobulin secretion, although pokeweed mitogen stimulation resulted in the development of cytoplasmic IgD and IgM. The lymphoid cell line established from these B lymphocytes primarily bore surface IgD, with a small population of cells also bearing surface IgM. These cells also had cytoplasmic immunoglobulin, primarily IgD. The cell line did not have a cytoplasmic pool of immunoglobulin for export and did not secrete immunoglobulin. This B lymphoid cell line is an in vitro analogue of the arrest in differentiation of the patient's B lymphocytes. The IgD-bearing phenotype may represent a normal transitional stage in the differentiation of B lymphocytes."}
{"id": "PMID:209465", "title": "Type C RNA virus-specific antibody in human systemic lupus erythematosus demonstrated by enzymoimmunoassay.", "content": "Postmortem study of proliferative glomerulonephritis associated with human systemic lumpus has previously shown that an antigen related to mammalian type C RNA viral core (p30) proteins is deposited in the renal glomerular lesions with human immunoglobulins in an immune-complex pattern. In the present work, human immunoglobulins were sequentially eluted from the lupus glomerular immune deposits and were assayed by a sensitive enzymoimmunoassay developed for the measurement of anti-p30 antibody activity against purified viral p30 proteins of mammalian type C viruses. Human immunoglobulins showing specific anti-p30 antibody activity, particularly against p30 antigen of feline endogenous virus RD-114 and to a smaller extent against p30 antigen of murine type C virus, were eluted by acid buffer from the glomerular immune deposits in two patients with lupus proliferative glomerulonephritis who have deposits of viral p30-related antigen in the same tissue lesions. This study adds support for the hypothesis that expression of type C viral antigen may be involved in the multifactorial pathogenesis of proliferative glomerulonephritis associated with human systemic lupus.", "contents": "Type C RNA virus-specific antibody in human systemic lupus erythematosus demonstrated by enzymoimmunoassay. Postmortem study of proliferative glomerulonephritis associated with human systemic lumpus has previously shown that an antigen related to mammalian type C RNA viral core (p30) proteins is deposited in the renal glomerular lesions with human immunoglobulins in an immune-complex pattern. In the present work, human immunoglobulins were sequentially eluted from the lupus glomerular immune deposits and were assayed by a sensitive enzymoimmunoassay developed for the measurement of anti-p30 antibody activity against purified viral p30 proteins of mammalian type C viruses. Human immunoglobulins showing specific anti-p30 antibody activity, particularly against p30 antigen of feline endogenous virus RD-114 and to a smaller extent against p30 antigen of murine type C virus, were eluted by acid buffer from the glomerular immune deposits in two patients with lupus proliferative glomerulonephritis who have deposits of viral p30-related antigen in the same tissue lesions. This study adds support for the hypothesis that expression of type C viral antigen may be involved in the multifactorial pathogenesis of proliferative glomerulonephritis associated with human systemic lupus."}
{"id": "PMID:209466", "title": "Generation of oncogenic type C viruses: rapidly leukemogenic viruses derived from C3H mouse cells in vivo and in vitro.", "content": "A type C virus was isolated from C3H/10T1/2 mouse cells in culture after activation with iododeoxyuridine. This virus was poorly infectious for mouse cells and did not cause tumors upon inoculation into newborn NIH Swiss mice. Variants with increased infectivity for mouse cells were then derived both in vivo and in vitro by selecting for variants able to grow to high titers. The highly infectious variants were found to induce mouse fibroblasts to grow in soft agar. When the viruses were inoculated into newborn NIH Swiss mice, 100% of the animals died of leukemia within 4 months. Solid tumors developed at the injection site. Both mouse-tropic and dualtropic viruses were isolated from the leukemic mice and plaque purified. The first group of viruses produced large syncytial plaques on rat XC cells and did not grow in mink cells. The viruses of the other group replicated well in both mouse and mink cells, producing morphologic changes similar to transformation but not XC syncytia; they, therefore, are members of the newly described MCF class of mouse type C viruses. Isolates from either group were highly leukemogenic on retesting, the mean latent period being 67 days for a mouse-tropic virus and 105 days for one of the dual-tropic viruses. The results led to the conclusion that the better a mouse type C virus grows in cell culture the more effective it is as a leukemogen. Further, it is possible to start with a weakly infectious, nonleukemogenic virus and to convert it to a rapidly replicating, highly leukemogenic virus by passage either in cell culture or in the animal. The availability of a defined series of viruses from a low-leukemia mouse strain that differ greatly in their biologic properties should facilitate studies of the molecular basis for the acquisition of type C virus oncogenicity.", "contents": "Generation of oncogenic type C viruses: rapidly leukemogenic viruses derived from C3H mouse cells in vivo and in vitro. A type C virus was isolated from C3H/10T1/2 mouse cells in culture after activation with iododeoxyuridine. This virus was poorly infectious for mouse cells and did not cause tumors upon inoculation into newborn NIH Swiss mice. Variants with increased infectivity for mouse cells were then derived both in vivo and in vitro by selecting for variants able to grow to high titers. The highly infectious variants were found to induce mouse fibroblasts to grow in soft agar. When the viruses were inoculated into newborn NIH Swiss mice, 100% of the animals died of leukemia within 4 months. Solid tumors developed at the injection site. Both mouse-tropic and dualtropic viruses were isolated from the leukemic mice and plaque purified. The first group of viruses produced large syncytial plaques on rat XC cells and did not grow in mink cells. The viruses of the other group replicated well in both mouse and mink cells, producing morphologic changes similar to transformation but not XC syncytia; they, therefore, are members of the newly described MCF class of mouse type C viruses. Isolates from either group were highly leukemogenic on retesting, the mean latent period being 67 days for a mouse-tropic virus and 105 days for one of the dual-tropic viruses. The results led to the conclusion that the better a mouse type C virus grows in cell culture the more effective it is as a leukemogen. Further, it is possible to start with a weakly infectious, nonleukemogenic virus and to convert it to a rapidly replicating, highly leukemogenic virus by passage either in cell culture or in the animal. The availability of a defined series of viruses from a low-leukemia mouse strain that differ greatly in their biologic properties should facilitate studies of the molecular basis for the acquisition of type C virus oncogenicity."}
{"id": "PMID:209467", "title": "New region of the simian virus 40 genome required for efficient viral transformation.", "content": "Viable mutants of simian virus 40 with deletions in three regions of the virus genome (map coordinates 0.21-0.17, 0.59-0.54, and 0.67-0.74) have been tested for their ability to transform rat fibroblasts to anchorage independence. Only those mutants whose deletions occur between 0.59 and 0.55 in the proximal part of the early region are defective in transforming ability. The most severely defective of these transform with less than one-hundredth the efficiency of wild type. They retain their defect when tested in Chinese hamster lung cells and when infection is initiated with viral DNA instead of intact virions. Complementation for transformation can be observed between these transformation-defective deletions and a simian virus 40 temperature-sensitive A mutant.", "contents": "New region of the simian virus 40 genome required for efficient viral transformation. Viable mutants of simian virus 40 with deletions in three regions of the virus genome (map coordinates 0.21-0.17, 0.59-0.54, and 0.67-0.74) have been tested for their ability to transform rat fibroblasts to anchorage independence. Only those mutants whose deletions occur between 0.59 and 0.55 in the proximal part of the early region are defective in transforming ability. The most severely defective of these transform with less than one-hundredth the efficiency of wild type. They retain their defect when tested in Chinese hamster lung cells and when infection is initiated with viral DNA instead of intact virions. Complementation for transformation can be observed between these transformation-defective deletions and a simian virus 40 temperature-sensitive A mutant."}
{"id": "PMID:209468", "title": "Identification of an Abelson murine leukemia virus-encoded protein present in transformed fibroblast and lymphoid cells.", "content": "Extracts from lymphoid and fibroblast cell lines transformed by Abelson murine leukemia virus (A-MuLV) contain a protein of molecular weight 120,000 (P120). Immunoprecipitation with specific sera shows that P120 contains regions homologous to the 5'-terminal segment of the MULV gag gene complex--p15, p12, and at least part of p30--but lacks detectable determinants of p10, reverse transcriptase, and the envelope glycoprotein. P120 is phosphorylated and has an intracellular half-life of 3--6 hr. In vitro translation of virion RNA from A-MuLV, with Moloney MuLV as helper, yields a product of molecular weight 120,000 with serological reactivity similar to that of the cellular P120. Translation of the RNA from the helper gave no P120. P120 is expressed in all lymphoid and fibroblastic cell lines we have tested that were transformed by A-MuLV but is not detectable in a lymphoid line in which the A-MuLV genome was established by infection but was not responsible for the transformation. Expression of P120 is selectively retained in clones of A-MuLV-transformed lymphocytes that convert to a nonproducer state after loss of expression of helper MuLV intracellular precursors. These results suggest that the P120 product of the A-MuLV genome may be responsible for maintenance of the transformed phenotype of lymphoid and fibroblast cells transformed by the virus.", "contents": "Identification of an Abelson murine leukemia virus-encoded protein present in transformed fibroblast and lymphoid cells. Extracts from lymphoid and fibroblast cell lines transformed by Abelson murine leukemia virus (A-MuLV) contain a protein of molecular weight 120,000 (P120). Immunoprecipitation with specific sera shows that P120 contains regions homologous to the 5'-terminal segment of the MULV gag gene complex--p15, p12, and at least part of p30--but lacks detectable determinants of p10, reverse transcriptase, and the envelope glycoprotein. P120 is phosphorylated and has an intracellular half-life of 3--6 hr. In vitro translation of virion RNA from A-MuLV, with Moloney MuLV as helper, yields a product of molecular weight 120,000 with serological reactivity similar to that of the cellular P120. Translation of the RNA from the helper gave no P120. P120 is expressed in all lymphoid and fibroblastic cell lines we have tested that were transformed by A-MuLV but is not detectable in a lymphoid line in which the A-MuLV genome was established by infection but was not responsible for the transformation. Expression of P120 is selectively retained in clones of A-MuLV-transformed lymphocytes that convert to a nonproducer state after loss of expression of helper MuLV intracellular precursors. These results suggest that the P120 product of the A-MuLV genome may be responsible for maintenance of the transformed phenotype of lymphoid and fibroblast cells transformed by the virus."}
{"id": "PMID:209469", "title": "Quantitative visualization of gamma-aminobutyric acid receptors in hippocampus and area dentata demonstrated by [3H]muscimol autoradiography.", "content": "Muscimol, a potent gamma-aminobutyric acid (GABA) agonist, was used in a radioactively labeled form for the quantitative localization of GABA receptors in the rat's hippocampus (CA(1) to CA(4)) and area dentata. [(3)H]Muscimol was injected directly in vivo or used in the incubation medium of tissue slices, and the tissues were then fixed and prepared for autoradiography. [(3)H]Muscimol-bound GABA receptors are weakly though evenly distributed over the fimbria of the fornix. There was a laminar distribution in CA(1) to CA(4) and the area dentata, with an increasing density of the GABA receptors in that order. The lowest density was found in the alveus of CA(1) and CA(2) and the highest in the stratum granulosum of the area dentata. The greatest density was found in the neuropil between granule cells, in which are found dendrites and the basket-like plexuses of the inhibitory GABA-containing local circuit neurons. The molecular layers of the area dentata, CA(1), and CA(2) also have a high density of GABA receptors, indicating a probable distribution over the dendrites of granule and pyramidal cells. The laminar distribution of GABA receptors in the hippocampus and area dentata is similar to the distributions of the GABA-synthesizing enzyme, glutamate decarboxylase, and of GABA previously published. Neurons with label of various density are found in the polymorphic cell layer of the area dentata, in the stratum radiatum of CA(3), and in CA(4). These are possibly the GABA-containing basket local circuit neurons.", "contents": "Quantitative visualization of gamma-aminobutyric acid receptors in hippocampus and area dentata demonstrated by [3H]muscimol autoradiography. Muscimol, a potent gamma-aminobutyric acid (GABA) agonist, was used in a radioactively labeled form for the quantitative localization of GABA receptors in the rat's hippocampus (CA(1) to CA(4)) and area dentata. [(3)H]Muscimol was injected directly in vivo or used in the incubation medium of tissue slices, and the tissues were then fixed and prepared for autoradiography. [(3)H]Muscimol-bound GABA receptors are weakly though evenly distributed over the fimbria of the fornix. There was a laminar distribution in CA(1) to CA(4) and the area dentata, with an increasing density of the GABA receptors in that order. The lowest density was found in the alveus of CA(1) and CA(2) and the highest in the stratum granulosum of the area dentata. The greatest density was found in the neuropil between granule cells, in which are found dendrites and the basket-like plexuses of the inhibitory GABA-containing local circuit neurons. The molecular layers of the area dentata, CA(1), and CA(2) also have a high density of GABA receptors, indicating a probable distribution over the dendrites of granule and pyramidal cells. The laminar distribution of GABA receptors in the hippocampus and area dentata is similar to the distributions of the GABA-synthesizing enzyme, glutamate decarboxylase, and of GABA previously published. Neurons with label of various density are found in the polymorphic cell layer of the area dentata, in the stratum radiatum of CA(3), and in CA(4). These are possibly the GABA-containing basket local circuit neurons."}
{"id": "PMID:209476", "title": "ACTH induced sodium appetite in the rat.", "content": "Subcutaneous injections of long-acting synthetic ACTH (5 U/day) caused a large increase in the intakes of both 0.5 M NaCl and water in rats. By the fifth day of treatment the rats were turning over an amount of sodium approximating their own total body sodium. The mineral appetite was specific for NaCl. Intakes of KCl, MgCl2 and CaCl2 were unchanged. ACTH was ineffective in adrenalectomized rats suggesting that the appetite was dependent on adrenal hormones.", "contents": "ACTH induced sodium appetite in the rat. Subcutaneous injections of long-acting synthetic ACTH (5 U/day) caused a large increase in the intakes of both 0.5 M NaCl and water in rats. By the fifth day of treatment the rats were turning over an amount of sodium approximating their own total body sodium. The mineral appetite was specific for NaCl. Intakes of KCl, MgCl2 and CaCl2 were unchanged. ACTH was ineffective in adrenalectomized rats suggesting that the appetite was dependent on adrenal hormones."}
{"id": "PMID:209477", "title": "ACTH and the stress-induced changes of lysine incorporation into brain and liver proteins.", "content": "When mice were subjected to footshock treatment and subsequently injected with [3H] lysine, the cerebral uptake of [3H] lysine, its incorporation into brain protein and the relative radioactivity (RR = protein radioactivity divided by amino acid radioactivity) were all increased. In the liver, footshocked mice showed decreased free lysine radioactivity, and increased protein radioactivity and relative radioactivity compared to quiet mice. The possibility that ACTH mediated these effects was investigated. The injection of saline had no effect in the brain but partially mimicked the footshock responses in the liver. Injections of ACTH 1--24 mimicked the effects of footshock in the brain, and further augmented the saline-induced effect on the RR in the liver. ACTH 4--10 increased the RR of brain protein, but produced no significant change in brain free lysine radioactivity or in any measure in the liver. Pretreatment of mice with the synthetic glucocorticoid, dexamethasone, did not enhance these effects and diminished the effect of ACTH 4--10 in the brain. ACTH treatment did not alter the profiles of brain polyribosomes. Lysine vasopressin, which is also released during stress, did not alter the incorporation of [3H] lysine into brain or liver protein, except at high doses when it decreased plasma radioactivity. These results suggest that secretion of ACTH at least partially mediates the stress-induced changes of [3H] lysine incorporation into brain and liver proteins, but that it is probably not the only factor involved.", "contents": "ACTH and the stress-induced changes of lysine incorporation into brain and liver proteins. When mice were subjected to footshock treatment and subsequently injected with [3H] lysine, the cerebral uptake of [3H] lysine, its incorporation into brain protein and the relative radioactivity (RR = protein radioactivity divided by amino acid radioactivity) were all increased. In the liver, footshocked mice showed decreased free lysine radioactivity, and increased protein radioactivity and relative radioactivity compared to quiet mice. The possibility that ACTH mediated these effects was investigated. The injection of saline had no effect in the brain but partially mimicked the footshock responses in the liver. Injections of ACTH 1--24 mimicked the effects of footshock in the brain, and further augmented the saline-induced effect on the RR in the liver. ACTH 4--10 increased the RR of brain protein, but produced no significant change in brain free lysine radioactivity or in any measure in the liver. Pretreatment of mice with the synthetic glucocorticoid, dexamethasone, did not enhance these effects and diminished the effect of ACTH 4--10 in the brain. ACTH treatment did not alter the profiles of brain polyribosomes. Lysine vasopressin, which is also released during stress, did not alter the incorporation of [3H] lysine into brain or liver protein, except at high doses when it decreased plasma radioactivity. These results suggest that secretion of ACTH at least partially mediates the stress-induced changes of [3H] lysine incorporation into brain and liver proteins, but that it is probably not the only factor involved."}
{"id": "PMID:209478", "title": "Alterations of spontaneous neuronal activity in the caudate-putamen, nucleus accumbens and amygdaloid complex of rats produced by D-amphetamine.", "content": "Changes in spontaneous neuronal activity in the caudate-putamen, accumbens nucleus and amygdaloid complex of immunobilized, locally anesthetized rats were recorded following intraperitoneal injection of 2.5 mg/kg d-amphetamine sulfate. In each site, d-amphetamine typically produced a prolonged depression of firing rate which, in most cases, occurred after an inital, brief potentiation of activity. However, the onset of the amphetamine-induced depression occurred signficantly later in the amygdala. Subsequent IP administration of either 5.0 mg/kg chlorpromazine or 2.0 mg/kg haloperidol reversed, to varying degrees, the amphetamine-induced depression of neuronal activity in each area. These results are discussed in terms of the known biochemical effects of amphetamine on catecholaminergic transmission and the alleged role of the nigro-neostriatal mesolimbic dopamine systems in the amphetamine behavioral response.", "contents": "Alterations of spontaneous neuronal activity in the caudate-putamen, nucleus accumbens and amygdaloid complex of rats produced by D-amphetamine. Changes in spontaneous neuronal activity in the caudate-putamen, accumbens nucleus and amygdaloid complex of immunobilized, locally anesthetized rats were recorded following intraperitoneal injection of 2.5 mg/kg d-amphetamine sulfate. In each site, d-amphetamine typically produced a prolonged depression of firing rate which, in most cases, occurred after an inital, brief potentiation of activity. However, the onset of the amphetamine-induced depression occurred signficantly later in the amygdala. Subsequent IP administration of either 5.0 mg/kg chlorpromazine or 2.0 mg/kg haloperidol reversed, to varying degrees, the amphetamine-induced depression of neuronal activity in each area. These results are discussed in terms of the known biochemical effects of amphetamine on catecholaminergic transmission and the alleged role of the nigro-neostriatal mesolimbic dopamine systems in the amphetamine behavioral response."}
{"id": "PMID:209479", "title": "A method for simultaneous recording of eight behavioral parameters related to monoamine neurotransmission.", "content": "In response to the increasing demand for refined techniques to record drug induced changes in motor activity we have designed and evaluated against observations an automatic test box that quantifies eight defined components of behaviour in rats. Activity, corresponding to the recordings from the commonly used photocell activity boxes. Total, and forward locomotion, expressing the actual distance the rat walks. Corner count, and corner time, reflecting the position of the animal in the box. Hole count, and hole time, expressing the reaction of the rat to an environmental stimulus i.e. holes in the bottom of the test box. Gnawing, which is a direct counting of the number of gnaws made by the animal. The recording parameters relate to our interest in behaviour influenced by monoamine neurotransmission and the result shows that the selected parameters are recorded with high reliability.", "contents": "A method for simultaneous recording of eight behavioral parameters related to monoamine neurotransmission. In response to the increasing demand for refined techniques to record drug induced changes in motor activity we have designed and evaluated against observations an automatic test box that quantifies eight defined components of behaviour in rats. Activity, corresponding to the recordings from the commonly used photocell activity boxes. Total, and forward locomotion, expressing the actual distance the rat walks. Corner count, and corner time, reflecting the position of the animal in the box. Hole count, and hole time, expressing the reaction of the rat to an environmental stimulus i.e. holes in the bottom of the test box. Gnawing, which is a direct counting of the number of gnaws made by the animal. The recording parameters relate to our interest in behaviour influenced by monoamine neurotransmission and the result shows that the selected parameters are recorded with high reliability."}
{"id": "PMID:209480", "title": "Atonia after carbachol microinjections near the locus coeruleus in cats.", "content": "The effect of microinjections of carbachol into the dorsolateral pontine tegmentum on the behaviour of cats is investigated. Injections of small amounts (50 and 500ng) of carbachol into the pontine reticular formation induced muscular atonia in otherwise awake animals. The atonia is not due to cholinergic stimulation of the noradrenergic cells of the locus coeruleus or the dorsolateral pons, since the most effective sites were situated ventrally to the locus coeruleus and alpha- and beta-adrenergic blocking agents did not affect the antonia. The results are discussed in view of the postulated role of the locus coeruleus in paradoxical sleep.", "contents": "Atonia after carbachol microinjections near the locus coeruleus in cats. The effect of microinjections of carbachol into the dorsolateral pontine tegmentum on the behaviour of cats is investigated. Injections of small amounts (50 and 500ng) of carbachol into the pontine reticular formation induced muscular atonia in otherwise awake animals. The atonia is not due to cholinergic stimulation of the noradrenergic cells of the locus coeruleus or the dorsolateral pons, since the most effective sites were situated ventrally to the locus coeruleus and alpha- and beta-adrenergic blocking agents did not affect the antonia. The results are discussed in view of the postulated role of the locus coeruleus in paradoxical sleep."}
{"id": "PMID:209481", "title": "Parallel changes in behaviour and hippocampal monoamine metabolism in rats after administration of ACTH-analogues.", "content": "Application of footshock during the acquisition trial of a one-trial passive avoidance test is associated with a rise in the concentration of serotonin in the hippocampi of rats 24 hr after termination of the acquisition trial. Rats subjected to amnesic treatment with carbon dioxide (CO2) immediately after footshock do not show this rise in the hippocampal concentration of serotonin. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 (7D-Phe), alleviate CO2-induced amnesia for the passive avoidance response when administered 1 hr before retrieval test 24 hr after acquisition. These peptides do not have anti-amnesic activity when given before acquistion. Another ACTH-analogue, ACTH 11-24 does not affect amnesia, given before either the acquisition or the retrieval test. The anti-amnesic effect of ACTH 4-10 AND ACTH 4-10 (7D-Phe), was correlated with a rise in the hippocampal serotonin concentration similar to that observed in non-amnesic animals. Pre-acquisition treatment with ACTH 4-10 or administration of ACTH 11-24 did not affect hippocampal serotonin concentrations. Changes in the hippocampal concentrations of noradrenaline, dopamine, tryptophan and tyrosine were not related to the behavioural activity of any of the peptides. It is suggested that alterations in hippocampal serotonin metabolism 24 hr after acquisition of a passive avoidance response are associated with the retrieveability of the passive avoidance response.", "contents": "Parallel changes in behaviour and hippocampal monoamine metabolism in rats after administration of ACTH-analogues. Application of footshock during the acquisition trial of a one-trial passive avoidance test is associated with a rise in the concentration of serotonin in the hippocampi of rats 24 hr after termination of the acquisition trial. Rats subjected to amnesic treatment with carbon dioxide (CO2) immediately after footshock do not show this rise in the hippocampal concentration of serotonin. The ACTH-analogues, ACTH 4-10 and ACTH 4-10 (7D-Phe), alleviate CO2-induced amnesia for the passive avoidance response when administered 1 hr before retrieval test 24 hr after acquisition. These peptides do not have anti-amnesic activity when given before acquistion. Another ACTH-analogue, ACTH 11-24 does not affect amnesia, given before either the acquisition or the retrieval test. The anti-amnesic effect of ACTH 4-10 AND ACTH 4-10 (7D-Phe), was correlated with a rise in the hippocampal serotonin concentration similar to that observed in non-amnesic animals. Pre-acquisition treatment with ACTH 4-10 or administration of ACTH 11-24 did not affect hippocampal serotonin concentrations. Changes in the hippocampal concentrations of noradrenaline, dopamine, tryptophan and tyrosine were not related to the behavioural activity of any of the peptides. It is suggested that alterations in hippocampal serotonin metabolism 24 hr after acquisition of a passive avoidance response are associated with the retrieveability of the passive avoidance response."}
{"id": "PMID:209482", "title": "Effect of stress on norepinephrine-stimulated cyclic AMP formation in brain slices.", "content": "Experiments were conducted to determine if stressful procedures, which increase brain norepinephrine (NE) release in rats, lower the responsiveness of central noradrenergic receptors as measured by the catecholamine (CA)-induced cAMP accumulation in hypothalamic and cerebral cortical slices. No conclusive evidence of subsensitivity was found after either acute or chronic electric footshock or continuous restraint. Failure to find a significant reduction after stress may have resulted from several methodological problems. These include (a) the inhibition of phosphodiesterase activity with isobutylmethylxanthine, which may have obscured possible adaptive changes in cAMP degradation and/or adenosine-dependent adrenergic receptors; (b) a low initial responsiveness to NE in these animals as suggested by the greater case in inducing supersensitivity with reserpine than subsensitivity with amphetamine; and (c) the use as a test agent of exogenous NE which may stimulate a far broader population of receptive sites in brain slices than are activated during stress by the local release of endogenous NE.", "contents": "Effect of stress on norepinephrine-stimulated cyclic AMP formation in brain slices. Experiments were conducted to determine if stressful procedures, which increase brain norepinephrine (NE) release in rats, lower the responsiveness of central noradrenergic receptors as measured by the catecholamine (CA)-induced cAMP accumulation in hypothalamic and cerebral cortical slices. No conclusive evidence of subsensitivity was found after either acute or chronic electric footshock or continuous restraint. Failure to find a significant reduction after stress may have resulted from several methodological problems. These include (a) the inhibition of phosphodiesterase activity with isobutylmethylxanthine, which may have obscured possible adaptive changes in cAMP degradation and/or adenosine-dependent adrenergic receptors; (b) a low initial responsiveness to NE in these animals as suggested by the greater case in inducing supersensitivity with reserpine than subsensitivity with amphetamine; and (c) the use as a test agent of exogenous NE which may stimulate a far broader population of receptive sites in brain slices than are activated during stress by the local release of endogenous NE."}
{"id": "PMID:209483", "title": "L-tryptophan inhibition of epinephrine-stimulated phosphorylase activity in vivo and in vitro.", "content": "The administration of L-tryptophan prevented the normal rise in blood sugar concentration that usually follows the injection of epinephrine into rats. Of the several possible mechanisms by which tryptophan could inhibit epinephrine-induced hyperglycemia, one might be that tryptophan prevented the activation of the enzyme, phosphorylase, which is an indirect result of epinephrine action on the liver. This report presents evidence supporting this hypothesis: (1) The injection of tryptophan (2.5 mM/kg) prevented epinephrine-induced glycogenolysis in the liver of rats by 100%. (2) The time courses of epinephrine-induced hyperglycemia and activation of phosphorylase in liver were nearly identical. (3) The injection of tryptophan completely inhibited (100%) the epinephrine-induced phosphorylase activation. (4) The addition of tryptophan in vitro completely inhibited (100%) the epinephrine-induced activation of phosphorylase. (5) Tryptophan inhibition of epinephrine-induced hyperglycemia occurs immediately after tryptophan administration. (6) The addition of cyclic AMP blocked the tryptophan inhibition of epinephrine-induced phosphorylase activation. This evidence suggests that tryptophan may inhibit epinephrine-induced hyperglycemia in rats by preventing the activation of liver phosphorylase.", "contents": "L-tryptophan inhibition of epinephrine-stimulated phosphorylase activity in vivo and in vitro. The administration of L-tryptophan prevented the normal rise in blood sugar concentration that usually follows the injection of epinephrine into rats. Of the several possible mechanisms by which tryptophan could inhibit epinephrine-induced hyperglycemia, one might be that tryptophan prevented the activation of the enzyme, phosphorylase, which is an indirect result of epinephrine action on the liver. This report presents evidence supporting this hypothesis: (1) The injection of tryptophan (2.5 mM/kg) prevented epinephrine-induced glycogenolysis in the liver of rats by 100%. (2) The time courses of epinephrine-induced hyperglycemia and activation of phosphorylase in liver were nearly identical. (3) The injection of tryptophan completely inhibited (100%) the epinephrine-induced phosphorylase activation. (4) The addition of tryptophan in vitro completely inhibited (100%) the epinephrine-induced activation of phosphorylase. (5) Tryptophan inhibition of epinephrine-induced hyperglycemia occurs immediately after tryptophan administration. (6) The addition of cyclic AMP blocked the tryptophan inhibition of epinephrine-induced phosphorylase activation. This evidence suggests that tryptophan may inhibit epinephrine-induced hyperglycemia in rats by preventing the activation of liver phosphorylase."}
{"id": "PMID:209484", "title": "Anticonvulsant activity and selective inhibition of NAD-dependent oxidations by 1,2,4-trisubstituted-5-imidazolones.", "content": "Nine 1-(3,4-dimethoxyphenylethyl)-2-methyl-4-(substituted benzylidene)-5-imidazolones were synthesized, characterized by their sharp melting points, elemental analyses and infrared spectra and evaluated for anticonvulsant activity. All 1,2,4-trisubstituted-5-imidazolones at a dose of 100 mg/kg i.p. possessed anticonvulsant activity and the degree of protection observed against pentylenetetrazol-induced convulsions in mice ranged from 20 to 60%. These 1,2,4-trisubstituted-5-imidazolones selectively inhibited in vitro oxidation of the nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, alpha-ketoglutarate and NADH by rat brain homogenates while the NAD-independent oxidation of succinate remained unaltered. The anti-convulsant activity possessed by 1,2,4-trisubstituted-5-imidazolones was unrelated with their ability to selectively inhibit respiratory activity of rat brain homogenates.", "contents": "Anticonvulsant activity and selective inhibition of NAD-dependent oxidations by 1,2,4-trisubstituted-5-imidazolones. Nine 1-(3,4-dimethoxyphenylethyl)-2-methyl-4-(substituted benzylidene)-5-imidazolones were synthesized, characterized by their sharp melting points, elemental analyses and infrared spectra and evaluated for anticonvulsant activity. All 1,2,4-trisubstituted-5-imidazolones at a dose of 100 mg/kg i.p. possessed anticonvulsant activity and the degree of protection observed against pentylenetetrazol-induced convulsions in mice ranged from 20 to 60%. These 1,2,4-trisubstituted-5-imidazolones selectively inhibited in vitro oxidation of the nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, alpha-ketoglutarate and NADH by rat brain homogenates while the NAD-independent oxidation of succinate remained unaltered. The anti-convulsant activity possessed by 1,2,4-trisubstituted-5-imidazolones was unrelated with their ability to selectively inhibit respiratory activity of rat brain homogenates."}
{"id": "PMID:209485", "title": "The psychotropic properties of estrogens.", "content": "In this review article clinical literature and experimental work from biochemistry, electro-encephalography and experimental psychology will be reported. Like the androgens and progestogens reviewed earlier, estrogens have psychotropic properties comparable to those of well-known psychotropic compounds. These are: improvement of psychological test results and increase in extraversion and decrease in neuroticism according to the Eysenck Personality Model (1964). Such effects are usually associated with the psychostimulants. The immediate effect on EEG of 4 mg estradiol valerate (single oral dose, male subjects), is a standard EEG profile similar to that of the tricyclic antidepressants. High dosages of estrogens have antidepressant properties clinically. In terms of psycho-pharmacological profiles, the estrogens seem to be a new type of psychotropic compound.", "contents": "The psychotropic properties of estrogens. In this review article clinical literature and experimental work from biochemistry, electro-encephalography and experimental psychology will be reported. Like the androgens and progestogens reviewed earlier, estrogens have psychotropic properties comparable to those of well-known psychotropic compounds. These are: improvement of psychological test results and increase in extraversion and decrease in neuroticism according to the Eysenck Personality Model (1964). Such effects are usually associated with the psychostimulants. The immediate effect on EEG of 4 mg estradiol valerate (single oral dose, male subjects), is a standard EEG profile similar to that of the tricyclic antidepressants. High dosages of estrogens have antidepressant properties clinically. In terms of psycho-pharmacological profiles, the estrogens seem to be a new type of psychotropic compound."}
{"id": "PMID:209490", "title": "Physostigmine alters onset but not duration of REM sleep in man.", "content": "Physostigmine (1.0mg) or placebo were administered intravenously over 1-h period to seven male normal volunteers beginning 35 min after sleep onset. The results indicate that physostigmine induced the onset of REM sleep but did not significantly alter the duration of individual REM sleep periods. Physostigmine significantly shortened the REM latency and the duration of the second nonREM period. After inducing the onset of the first REM period(s); physostigmine also appeared to advance succeeding REM-nonREM sleep cycles relative to sleep onset even when the duration of each cycle was unaffected.", "contents": "Physostigmine alters onset but not duration of REM sleep in man. Physostigmine (1.0mg) or placebo were administered intravenously over 1-h period to seven male normal volunteers beginning 35 min after sleep onset. The results indicate that physostigmine induced the onset of REM sleep but did not significantly alter the duration of individual REM sleep periods. Physostigmine significantly shortened the REM latency and the duration of the second nonREM period. After inducing the onset of the first REM period(s); physostigmine also appeared to advance succeeding REM-nonREM sleep cycles relative to sleep onset even when the duration of each cycle was unaffected."}
{"id": "PMID:209498", "title": "An antiserum against 9-deoxy-6,9-epoxy-PGF1alpha recognizes and binds PGI2 (prostacyclin).", "content": "Antibodies were prepared against 9-deoxy-6,9-epoxy-PGF1alpha, the 5,6-dihydro analog of prostacyclin (PGI2). By using as the hapten, this structurally similar, stable analog, an antibody population was developed which recognized PGI2 and reversed its influence on platelet aggregation. The antibodies also opposed the normal effect of PGI2 on the cAMP and thromboxane B2 levels during aggregation. By anticipating the cross reaction between the analog and PGI2 and by considering it beneficial, the problem of raising antibodies against an unstable compound has been circumvented.", "contents": "An antiserum against 9-deoxy-6,9-epoxy-PGF1alpha recognizes and binds PGI2 (prostacyclin). Antibodies were prepared against 9-deoxy-6,9-epoxy-PGF1alpha, the 5,6-dihydro analog of prostacyclin (PGI2). By using as the hapten, this structurally similar, stable analog, an antibody population was developed which recognized PGI2 and reversed its influence on platelet aggregation. The antibodies also opposed the normal effect of PGI2 on the cAMP and thromboxane B2 levels during aggregation. By anticipating the cross reaction between the analog and PGI2 and by considering it beneficial, the problem of raising antibodies against an unstable compound has been circumvented."}
{"id": "PMID:209499", "title": "A rapid, simple determination of plasma cyclic AMP.", "content": "Plasma cyclic AMP content was determined without being extracted, using binding protein obtained from rat liver. EDTA was suitable as an anticoagulant for cyclic AMP estimation. Cyclic AMP further added to EDTA plasma was able to be estimated. The estimated values by plasma dilution were almost the same as the expected values. It was thought that the direct assay was useful for determination of plasma cyclic AMP. Isoproterenol (50 microgram/kg, iv) produced an increase of plasma cyclic AMP level accompanied with a decrease of blood pressure and an increase of heart rate in anesthetized dogs. Cyclic AMP level of peripheral venous plasma was 18.6 +/- 1.32 p mole/ml in human (N=25), 21.6 +/- 3.04 P mole/ml in dogs (N=7) and 50.6 +/- 4.59 p mole/ml in rabbit (N=9). Plasma cyclic AMP level of rabbit was higher than those of human and dog.", "contents": "A rapid, simple determination of plasma cyclic AMP. Plasma cyclic AMP content was determined without being extracted, using binding protein obtained from rat liver. EDTA was suitable as an anticoagulant for cyclic AMP estimation. Cyclic AMP further added to EDTA plasma was able to be estimated. The estimated values by plasma dilution were almost the same as the expected values. It was thought that the direct assay was useful for determination of plasma cyclic AMP. Isoproterenol (50 microgram/kg, iv) produced an increase of plasma cyclic AMP level accompanied with a decrease of blood pressure and an increase of heart rate in anesthetized dogs. Cyclic AMP level of peripheral venous plasma was 18.6 +/- 1.32 p mole/ml in human (N=25), 21.6 +/- 3.04 P mole/ml in dogs (N=7) and 50.6 +/- 4.59 p mole/ml in rabbit (N=9). Plasma cyclic AMP level of rabbit was higher than those of human and dog."}
{"id": "PMID:209500", "title": "[Immunological and structural properties of Rous sarcoma virus-transformed and tumor cells].", "content": "We compared the capacity of both normal and Rous sarcoma virus (RSV)-transformed chicken embryo fibroblast (CEF) cells as well as Rous sarcoma (RS) tumor cells to serve as targets in anti-tumor immunity assays. These studies showed that sera from tumor-bearing donors were able to stain transformed CEF more efficiently than RS cells as detected by immunofluorescence. In contrast, antiserum against the major viral glycoprotein, gp 85, stained a higher percentage of RS than transformed cells. Normal CEF cells, which served as controls, were essentially non-reactive with the immune system as judged by this type of assay. We observed that RS cells are considerably larger and contain far higher levels of protein than either normal or transformed CEF. Scanning electron microscopy revealed both the RS cells and transformed CEF to be rich in surface ruffles, blebs and microvilli as distinguished from the flattened, fusiform appearance of normal CEF cells.", "contents": "[Immunological and structural properties of Rous sarcoma virus-transformed and tumor cells]. We compared the capacity of both normal and Rous sarcoma virus (RSV)-transformed chicken embryo fibroblast (CEF) cells as well as Rous sarcoma (RS) tumor cells to serve as targets in anti-tumor immunity assays. These studies showed that sera from tumor-bearing donors were able to stain transformed CEF more efficiently than RS cells as detected by immunofluorescence. In contrast, antiserum against the major viral glycoprotein, gp 85, stained a higher percentage of RS than transformed cells. Normal CEF cells, which served as controls, were essentially non-reactive with the immune system as judged by this type of assay. We observed that RS cells are considerably larger and contain far higher levels of protein than either normal or transformed CEF. Scanning electron microscopy revealed both the RS cells and transformed CEF to be rich in surface ruffles, blebs and microvilli as distinguished from the flattened, fusiform appearance of normal CEF cells."}
{"id": "PMID:209501", "title": "The mecanism of cementing line formation in the bones of cestrum-fed chicks.", "content": "Chicks fed a rachitogenic diet for five weeks after hatching were then treated with a daily oral dose of 1,000 I.U. Vitamin D3 or a 1% addition to the feed of powdered leaves of Cestrum diurnum for periods of 1, 2, 4, 8, 16 and 30 days. Comparative studies were made on stained sections, microradiographs of undermineralized sections and alpharadiographs of demineralized sections. The present dose of Cestrum diurnum caused at first, a rapid maturation and mineralization of the epiphyseal cartilage and an intense growth and osteocytic osteolysis in the diaphysis of the tibia and femur. After 8 days however, growth decreased and the diaphysis gradually became petrotic. Under these conditions, the osteocytes degenerated and died. The areas of polysaccharide-rich, low density matrix which surrounded them, decreased gradually to become cementing lines, persistent after 30 days.", "contents": "The mecanism of cementing line formation in the bones of cestrum-fed chicks. Chicks fed a rachitogenic diet for five weeks after hatching were then treated with a daily oral dose of 1,000 I.U. Vitamin D3 or a 1% addition to the feed of powdered leaves of Cestrum diurnum for periods of 1, 2, 4, 8, 16 and 30 days. Comparative studies were made on stained sections, microradiographs of undermineralized sections and alpharadiographs of demineralized sections. The present dose of Cestrum diurnum caused at first, a rapid maturation and mineralization of the epiphyseal cartilage and an intense growth and osteocytic osteolysis in the diaphysis of the tibia and femur. After 8 days however, growth decreased and the diaphysis gradually became petrotic. Under these conditions, the osteocytes degenerated and died. The areas of polysaccharide-rich, low density matrix which surrounded them, decreased gradually to become cementing lines, persistent after 30 days."}
{"id": "PMID:209505", "title": "Barbiturate dependence in mice: evidence for beta-adrenergic receptor proliferation in brain.", "content": "C57BL/6J and DBA/2J inbred mice were assayed for beta-adrenergic receptor density following seven days of chronic phenobarbital intoxication. These physically dependent mice showed a greater brain receptor density than did the control, while acute intoxication to phenobarbital produced no significant effects. C57BL/6J mice showed a higher average receptor density than did the DBA/2J mice under all conditions. These findings support the hypothesis that chronic barbiturate intoxication leads to a receptor supersensitivity which may play a role in the phenomena of functional tolerance and physical dependence.", "contents": "Barbiturate dependence in mice: evidence for beta-adrenergic receptor proliferation in brain. C57BL/6J and DBA/2J inbred mice were assayed for beta-adrenergic receptor density following seven days of chronic phenobarbital intoxication. These physically dependent mice showed a greater brain receptor density than did the control, while acute intoxication to phenobarbital produced no significant effects. C57BL/6J mice showed a higher average receptor density than did the DBA/2J mice under all conditions. These findings support the hypothesis that chronic barbiturate intoxication leads to a receptor supersensitivity which may play a role in the phenomena of functional tolerance and physical dependence."}
{"id": "PMID:209506", "title": "The effect of dobutamine on rat cardiac cyclic AMP, phosphorylase a and force of contraction.", "content": "Dobutamine produced a dose-dependent increase in cardiac cyclic AMP, % phosphorylase a and contractile force in the isolated perfused rat heart. Cyclic AMP increased prior to the increase in % phosphorylase a and prior to or concomitant with the increase in force. Similar results were obtained with isoproterenol except that the effects of isoproterenol occurred slightly earlier. The efficacy of both amines was approximately the same but dobutamine was was about 1/45 as potent as isoproterenol.", "contents": "The effect of dobutamine on rat cardiac cyclic AMP, phosphorylase a and force of contraction. Dobutamine produced a dose-dependent increase in cardiac cyclic AMP, % phosphorylase a and contractile force in the isolated perfused rat heart. Cyclic AMP increased prior to the increase in % phosphorylase a and prior to or concomitant with the increase in force. Similar results were obtained with isoproterenol except that the effects of isoproterenol occurred slightly earlier. The efficacy of both amines was approximately the same but dobutamine was was about 1/45 as potent as isoproterenol."}
{"id": "PMID:209507", "title": "Some characteristics of a natural infection by parainfluenza-3 virus in a group of calves.", "content": "Parainfluenza-3 (Pi3) virus infection in a group of 25 calves is described. The virus was isolated from the lungs of four calve at days 6, 7, 13 and 55 after they were housed together at birth. Intracytoplasmic inclusion bodies were seen by light microscopy in bronchial and bronchiolar epithelial cells of two of these calves. Virus infected cells were detected by electron microscopy in three of the four calves. Haemagglutination inhibition antibodies to Pi3 virus were found in the sera of the calves. Despite the virus being present in the group from one week, a significant increase in antibody titre was found in only two animals although all the calves were in contact with each other during the study period. The pulmonary lesions in the four infected calves consisted of a bronchitis and bronchiolitis with infiltration of the walls and lumena of these structures by neutrophils and an adjacent neutrophil infiltration of alveoli some of which were collapsed.", "contents": "Some characteristics of a natural infection by parainfluenza-3 virus in a group of calves. Parainfluenza-3 (Pi3) virus infection in a group of 25 calves is described. The virus was isolated from the lungs of four calve at days 6, 7, 13 and 55 after they were housed together at birth. Intracytoplasmic inclusion bodies were seen by light microscopy in bronchial and bronchiolar epithelial cells of two of these calves. Virus infected cells were detected by electron microscopy in three of the four calves. Haemagglutination inhibition antibodies to Pi3 virus were found in the sera of the calves. Despite the virus being present in the group from one week, a significant increase in antibody titre was found in only two animals although all the calves were in contact with each other during the study period. The pulmonary lesions in the four infected calves consisted of a bronchitis and bronchiolitis with infiltration of the walls and lumena of these structures by neutrophils and an adjacent neutrophil infiltration of alveoli some of which were collapsed."}
{"id": "PMID:209525", "title": "[ECG signs of pulmonary embolism caused by lymphography injected contrast oil (author's transl)].", "content": "Authors have reported ECG signs of pulmonary embolism caused by lymphography injected contrast oil. Signs indicative of transitory right ventricular strain were observed in the ECG in 17 of 30 clinically symptom-free patients.", "contents": "[ECG signs of pulmonary embolism caused by lymphography injected contrast oil (author's transl)]. Authors have reported ECG signs of pulmonary embolism caused by lymphography injected contrast oil. Signs indicative of transitory right ventricular strain were observed in the ECG in 17 of 30 clinically symptom-free patients."}
{"id": "PMID:209532", "title": "The clinical importance of anaerobic bacteria in wound infections after gastrointestinal surgery.", "content": "Wound cultures from 54 patients with infections after gastrointestinal surgery were examined. Cultures from wounds after surgery on the upper gastrointestinal tract grew few organisms, mainly aerobic gram-positive cocci. Culture from wounds on the lower gastrointestinal tract grew strains of bacteria, aerobic and anaerobic gram-negative rods dominating. Indirect immunofluorescence studies on acute and convalescent phase sera showed significant immune response against Bacteroides fragilis in a majority of cases. Immune response against anaerobic cocci was seldom found. Very high antibody titres against Clostridium perfringens were often found, both in patients' and control sera.", "contents": "The clinical importance of anaerobic bacteria in wound infections after gastrointestinal surgery. Wound cultures from 54 patients with infections after gastrointestinal surgery were examined. Cultures from wounds after surgery on the upper gastrointestinal tract grew few organisms, mainly aerobic gram-positive cocci. Culture from wounds on the lower gastrointestinal tract grew strains of bacteria, aerobic and anaerobic gram-negative rods dominating. Indirect immunofluorescence studies on acute and convalescent phase sera showed significant immune response against Bacteroides fragilis in a majority of cases. Immune response against anaerobic cocci was seldom found. Very high antibody titres against Clostridium perfringens were often found, both in patients' and control sera."}
{"id": "PMID:209529", "title": "Deviation of plasmatic aldosterone and significance of the stimulating (ACTH-cortrosyn) and inhibitory (propranolol) effects in hypertension and cardiovascular pathology.", "content": "Starting from the interference between the renin-angiotensin-aldosterone (RAA) system and cardiovascular pathology in arterial hypertension (AH) we have made a correlative study of the cardiovascular system and plasmatic aldosterone in normal and hypertensive subjects under conditions of stimulation (ACTH) and inhibition (propranolol). After administration of ACTH (one of the physiologic mediators of stress) increased values for plasmatic aldosterone were found. Negative cardiovascular effect: arrhthmia, angor, AH, cardiac asthma, under the condition of preexisting cardiovascular pathology or altered steroidogensis, were also noticed. Inhibition with propranolol does not have conclusive effects in AH with normal aldosterone. The best effect were noticed in that hypertension which implies the RAA pressor system in its pathogeny, irrespective of etiology, the reduction AT occurring in parallel with decline in plasmatic aldosterone values and total peripheral resistance (RPT). Administration of propranolol in AH with activated RAA system irrespective of etiology represents a pathogenic treatment able to prevent efficiently the major complications of AH.", "contents": "Deviation of plasmatic aldosterone and significance of the stimulating (ACTH-cortrosyn) and inhibitory (propranolol) effects in hypertension and cardiovascular pathology. Starting from the interference between the renin-angiotensin-aldosterone (RAA) system and cardiovascular pathology in arterial hypertension (AH) we have made a correlative study of the cardiovascular system and plasmatic aldosterone in normal and hypertensive subjects under conditions of stimulation (ACTH) and inhibition (propranolol). After administration of ACTH (one of the physiologic mediators of stress) increased values for plasmatic aldosterone were found. Negative cardiovascular effect: arrhthmia, angor, AH, cardiac asthma, under the condition of preexisting cardiovascular pathology or altered steroidogensis, were also noticed. Inhibition with propranolol does not have conclusive effects in AH with normal aldosterone. The best effect were noticed in that hypertension which implies the RAA pressor system in its pathogeny, irrespective of etiology, the reduction AT occurring in parallel with decline in plasmatic aldosterone values and total peripheral resistance (RPT). Administration of propranolol in AH with activated RAA system irrespective of etiology represents a pathogenic treatment able to prevent efficiently the major complications of AH."}
{"id": "PMID:209533", "title": "Pharmacokinetic and therapeutic studies of pivmecillinam in patients with normal and impaired renal function.", "content": "Pivmecillinam which is the oral form of mecillinam was evaluated by treatment of 26 patients presenting various types of urinary tract infections and by prophylactic treatment of 12 patients. Pivmecillinam given in a daily dosage of 1.2 g for periods of 1 to 56 weeks was well tolerated in all of the patients including those with impaired renal function without any dose reduction. The original bacterial strain in the urine was eradicated in 100% of the cases. Two patients had a superinfection and 4 had a recurrence during a 3-month follow-up period. The oral absorption of pivmecillinam was investigated in 15 patients with normal or slightly reduced renal function and in 5 patients on maintenance hemodialysis. High serum levels were achieved within 1 to 2 h after administration. Patients with reduced renal function showed retarded elimination rates, suggesting that the dose should be adjusted in this category of patients.", "contents": "Pharmacokinetic and therapeutic studies of pivmecillinam in patients with normal and impaired renal function. Pivmecillinam which is the oral form of mecillinam was evaluated by treatment of 26 patients presenting various types of urinary tract infections and by prophylactic treatment of 12 patients. Pivmecillinam given in a daily dosage of 1.2 g for periods of 1 to 56 weeks was well tolerated in all of the patients including those with impaired renal function without any dose reduction. The original bacterial strain in the urine was eradicated in 100% of the cases. Two patients had a superinfection and 4 had a recurrence during a 3-month follow-up period. The oral absorption of pivmecillinam was investigated in 15 patients with normal or slightly reduced renal function and in 5 patients on maintenance hemodialysis. High serum levels were achieved within 1 to 2 h after administration. Patients with reduced renal function showed retarded elimination rates, suggesting that the dose should be adjusted in this category of patients."}
{"id": "PMID:209530", "title": "Serum electrophoretic lipoprotein factors and pseudocholinesterase activity in thyroid disease.", "content": "Decreased levels of serum cholesterol and beta-lipoproteins occurring in hyperthyroidism were found to be accompanied by an enchanced activity of pseudocholinesterase, while in patients with myxedema, the pathologically increased levels of serum cholesterol and beta-lipoproteins were associated with diminished serum pseudocholinesterase activity. The percentage of the pre-beta fraction was found to be increased in both hypo- and hyperthyroid patients, but mechanisms leading to this change are probably different in the two pathological conditions. The behaviour of cholesterol and pseudocholinesterase activity and especially the ratio between these paramameters might be used for the diagnosis of thyroid disease and for the control of therapeutic efficiency.", "contents": "Serum electrophoretic lipoprotein factors and pseudocholinesterase activity in thyroid disease. Decreased levels of serum cholesterol and beta-lipoproteins occurring in hyperthyroidism were found to be accompanied by an enchanced activity of pseudocholinesterase, while in patients with myxedema, the pathologically increased levels of serum cholesterol and beta-lipoproteins were associated with diminished serum pseudocholinesterase activity. The percentage of the pre-beta fraction was found to be increased in both hypo- and hyperthyroid patients, but mechanisms leading to this change are probably different in the two pathological conditions. The behaviour of cholesterol and pseudocholinesterase activity and especially the ratio between these paramameters might be used for the diagnosis of thyroid disease and for the control of therapeutic efficiency."}
{"id": "PMID:209534", "title": "Septicemia and meningitis caused by Fusobacterium aquatile.", "content": "A case of septicemia and meningitis caused by Fusobacterium aquatile is described. The insidious onset of the megningitis and occurrence of multiple cranial nerve affections were outstanding features. In spite of adequate antibiotic treatment the course was protracted, and the outcome was permanent damage to 3 of the affected cranial nerves.", "contents": "Septicemia and meningitis caused by Fusobacterium aquatile. A case of septicemia and meningitis caused by Fusobacterium aquatile is described. The insidious onset of the megningitis and occurrence of multiple cranial nerve affections were outstanding features. In spite of adequate antibiotic treatment the course was protracted, and the outcome was permanent damage to 3 of the affected cranial nerves."}
{"id": "PMID:209535", "title": "The changed epidemiology of hepatitis A infection in Scandinavia.", "content": "The prevalence of antibodies against hepatitis A virus (anti-HAV) was studied in a Swedish city population. A great difference was observed in different age groups. Anti-HAV was not found in the serum of young individuals while the prevalence was high in older ages (87% in individuals 60 years or older). This pattern of hepatitis A exposure is quite different from that reported for instance from the Mediterranean area and may indicate a very low frequency of hepatitis A exposure in Scandinavia today. The high prevalence of anti-HAV in older Swedes possibly reflects hepatitis A exposure in childhood during World War I and II when hepatitis A was more common.", "contents": "The changed epidemiology of hepatitis A infection in Scandinavia. The prevalence of antibodies against hepatitis A virus (anti-HAV) was studied in a Swedish city population. A great difference was observed in different age groups. Anti-HAV was not found in the serum of young individuals while the prevalence was high in older ages (87% in individuals 60 years or older). This pattern of hepatitis A exposure is quite different from that reported for instance from the Mediterranean area and may indicate a very low frequency of hepatitis A exposure in Scandinavia today. The high prevalence of anti-HAV in older Swedes possibly reflects hepatitis A exposure in childhood during World War I and II when hepatitis A was more common."}
{"id": "PMID:209536", "title": "Effect of (+)catechin on connective tissue.", "content": "The effect of (+)catechin on connective tissue was studied in organ cultures of chick embryo tibiae and after in vivo injection in rats and mice. Collagen biosynthesis and hydroxylation of 14C-Pro-labelled protocollagen in vitro by protocollagen proline hydroxylase (PPH) were inhibited. In vivo, a slight decrease in the biosynthesis of collagen and in the PPH activity in skin of rats and mice was noticed as an effect of (+)catechin. No effect of the drug was observed on the incorporation of 14C-D-glucosamine by chick embryo tibiae. Increased urinary excretion of acid mucopolysaccharide metabolites by the mice injected with (+)catechin was observed.", "contents": "Effect of (+)catechin on connective tissue. The effect of (+)catechin on connective tissue was studied in organ cultures of chick embryo tibiae and after in vivo injection in rats and mice. Collagen biosynthesis and hydroxylation of 14C-Pro-labelled protocollagen in vitro by protocollagen proline hydroxylase (PPH) were inhibited. In vivo, a slight decrease in the biosynthesis of collagen and in the PPH activity in skin of rats and mice was noticed as an effect of (+)catechin. No effect of the drug was observed on the incorporation of 14C-D-glucosamine by chick embryo tibiae. Increased urinary excretion of acid mucopolysaccharide metabolites by the mice injected with (+)catechin was observed."}
{"id": "PMID:209537", "title": "[Primary stenosing cholangitis].", "content": "Five cases of sclerosing cholangitis are recorded from 3697 biliary operations. Two patients had a cancerous course and 1 associated ulcerative colitis. The first two cases could be classified as primary sclerosing cholangitis. They are described. The pathogenetic mechanisms and treatment of this affection are discussed.", "contents": "[Primary stenosing cholangitis]. Five cases of sclerosing cholangitis are recorded from 3697 biliary operations. Two patients had a cancerous course and 1 associated ulcerative colitis. The first two cases could be classified as primary sclerosing cholangitis. They are described. The pathogenetic mechanisms and treatment of this affection are discussed."}
{"id": "PMID:209538", "title": "[Surgical treatment of syndactylia].", "content": "In a review of over 100 surgical procedures on the hand in the pediatric age group during the past 4 years, experience in the treatment of syndactyly of the hand is discussed. Due to their structural differences, exogenous acrosyndactylies are to be distinguished from the genetically determined cutaneous and osseous syndactyly. Early separation of thumb, index and fifth finger ensures grip function and improves psychointellectual development. Scar syndactyly is avoidable given an appropriate technique for formation of the interdigital commissure and if triangular flaps for long digits are used.", "contents": "[Surgical treatment of syndactylia]. In a review of over 100 surgical procedures on the hand in the pediatric age group during the past 4 years, experience in the treatment of syndactyly of the hand is discussed. Due to their structural differences, exogenous acrosyndactylies are to be distinguished from the genetically determined cutaneous and osseous syndactyly. Early separation of thumb, index and fifth finger ensures grip function and improves psychointellectual development. Scar syndactyly is avoidable given an appropriate technique for formation of the interdigital commissure and if triangular flaps for long digits are used."}
{"id": "PMID:209539", "title": "[Progress in clinical oncology 1978].", "content": "A short survey of recent progress in the diagnosis and pharmacotherapy of neoplastic diseases is conducted, with special mention of measurement of hormone receptors, needle biopsy, tactics and strategy of drug therapy, and new drugs. The importance of several forms of cooperation is stressed: cooperation between doctor and patient, between hospital physician and town physician, interdisciplinary cooperation, and cooperative clinical studies. Adjuvant chemotherapy and immunotherapy are new methods under study. The problems arising in the wake of progress in medical oncology and the ever increasing use of chemotherapy are loss of individual initiative in physicians working with protocols, and prohibitive costs are diagnostic and therapeutic procedures become more sophisticated.", "contents": "[Progress in clinical oncology 1978]. A short survey of recent progress in the diagnosis and pharmacotherapy of neoplastic diseases is conducted, with special mention of measurement of hormone receptors, needle biopsy, tactics and strategy of drug therapy, and new drugs. The importance of several forms of cooperation is stressed: cooperation between doctor and patient, between hospital physician and town physician, interdisciplinary cooperation, and cooperative clinical studies. Adjuvant chemotherapy and immunotherapy are new methods under study. The problems arising in the wake of progress in medical oncology and the ever increasing use of chemotherapy are loss of individual initiative in physicians working with protocols, and prohibitive costs are diagnostic and therapeutic procedures become more sophisticated."}
{"id": "PMID:209541", "title": "Aminophylline increases cerebral metabolic rate and decreases anoxic survival in young mice.", "content": "In weanling mice treated with pharmacologic doses of aminophylline, the concentrations of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in the brain increased 44 and 36 percent, respectively, and the cerebral metabolic rate was three times that in controls. In neonatal mice, therapeutic doses of aminophylline greatly decreased the rate of anoxic survival in vivo and the duration of gasping of the isolated head. The findings suggest caution in the use of this drug and other methylxanthines in hypoxic human newborns.", "contents": "Aminophylline increases cerebral metabolic rate and decreases anoxic survival in young mice. In weanling mice treated with pharmacologic doses of aminophylline, the concentrations of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in the brain increased 44 and 36 percent, respectively, and the cerebral metabolic rate was three times that in controls. In neonatal mice, therapeutic doses of aminophylline greatly decreased the rate of anoxic survival in vivo and the duration of gasping of the isolated head. The findings suggest caution in the use of this drug and other methylxanthines in hypoxic human newborns."}
{"id": "PMID:209543", "title": "[Primary hyperaldosteronism with paroxysmal arterial hypertension. Apropos of 2 operated cases].", "content": "Primary hyperaldosteronism usually causes moderate hypertension. It is rare to note as in our two patients intermittent attacks of paroxysmal hypertension. The diagnosis of aldosteronism will be suspected on the finding of persistent hypokalemia with acidosis. It will be confirmed by laboratory examinations severe fall in plasma renin activity and rise in aldosterone in the adrenal veins. To determine the affected side, one may carry out adrenal phlebography which is a difficult technic, and/or a scan using iodine cholesterol which is benign and precise. Surgery with removal of the adenomatous hyperplasia in one case and of an adenoma in the other, gave one very good result.", "contents": "[Primary hyperaldosteronism with paroxysmal arterial hypertension. Apropos of 2 operated cases]. Primary hyperaldosteronism usually causes moderate hypertension. It is rare to note as in our two patients intermittent attacks of paroxysmal hypertension. The diagnosis of aldosteronism will be suspected on the finding of persistent hypokalemia with acidosis. It will be confirmed by laboratory examinations severe fall in plasma renin activity and rise in aldosterone in the adrenal veins. To determine the affected side, one may carry out adrenal phlebography which is a difficult technic, and/or a scan using iodine cholesterol which is benign and precise. Surgery with removal of the adenomatous hyperplasia in one case and of an adenoma in the other, gave one very good result."}
{"id": "PMID:209544", "title": "[Urogenital infections and mycoplasms].", "content": "The role of genital mycoplasmas, e.g. M. hominis and U. urealyticum in urogenital infections is controversial. 120 samples were taken in 95 men and 25 women with urogenital infections and examined in the laboratory. Mycoplasmas were found in about 32% of men and 52% of women. M. Hominis is often associated with gonococcal infection and seems to play only a secondary role. The frequent isolation of U. urealyticum in various types of urethritis (gonococcal and non-gonococcal) is roughly the same. In the absence of a control investigation in healthy subjects, it is not possible to say whether it plays any role in urethritis.", "contents": "[Urogenital infections and mycoplasms]. The role of genital mycoplasmas, e.g. M. hominis and U. urealyticum in urogenital infections is controversial. 120 samples were taken in 95 men and 25 women with urogenital infections and examined in the laboratory. Mycoplasmas were found in about 32% of men and 52% of women. M. Hominis is often associated with gonococcal infection and seems to play only a secondary role. The frequent isolation of U. urealyticum in various types of urethritis (gonococcal and non-gonococcal) is roughly the same. In the absence of a control investigation in healthy subjects, it is not possible to say whether it plays any role in urethritis."}
{"id": "PMID:209547", "title": "[Observations apropos 500 case reports of upper gastrointestinal hemorrhages].", "content": "In this study of 500 cases of bleeding from the upper digestive tract, the importance of emergency fibre endoscopy is emphasised. It is in fact the only way to demonstrate acute gastro-duodenal lesions which are very frequent, especially during post-operative intensive care. As far as treatment is concerned, the interest of gastric lavage with ice-cold drinks is emphasised in hemostasis. As far as surgery is concerned, the indications are now well known depending on the rate of transfusion during the first few hours and the etiology. In chronic duodenal ulcers, vagotomy, pyloroplasty and suture of the ulcer have always given good results. This is also the case with acute ulcers. On the other hand, in gastric ulcers, gastrectomy remains the treatment of choice. When bleeding is due to oesophageal varices, surgery is only indicated in exceptional cases.", "contents": "[Observations apropos 500 case reports of upper gastrointestinal hemorrhages]. In this study of 500 cases of bleeding from the upper digestive tract, the importance of emergency fibre endoscopy is emphasised. It is in fact the only way to demonstrate acute gastro-duodenal lesions which are very frequent, especially during post-operative intensive care. As far as treatment is concerned, the interest of gastric lavage with ice-cold drinks is emphasised in hemostasis. As far as surgery is concerned, the indications are now well known depending on the rate of transfusion during the first few hours and the etiology. In chronic duodenal ulcers, vagotomy, pyloroplasty and suture of the ulcer have always given good results. This is also the case with acute ulcers. On the other hand, in gastric ulcers, gastrectomy remains the treatment of choice. When bleeding is due to oesophageal varices, surgery is only indicated in exceptional cases."}
{"id": "PMID:209567", "title": "Ectopic adrenocorticotrophic hormone syndrome. A case report.", "content": "Excessive production of adrenocorticotrophic hormone (ACTH) by oat cell carcinomas and carcinoid tumours of the lung has been well documented. Florid cases of Cushing's syndrome secondary to the excessive production of ACTH by the tumour are rare. In this article 2 cases of florid Cushing's syndrome associated with oat cell carcinoma are described.", "contents": "Ectopic adrenocorticotrophic hormone syndrome. A case report. Excessive production of adrenocorticotrophic hormone (ACTH) by oat cell carcinomas and carcinoid tumours of the lung has been well documented. Florid cases of Cushing's syndrome secondary to the excessive production of ACTH by the tumour are rare. In this article 2 cases of florid Cushing's syndrome associated with oat cell carcinoma are described."}
{"id": "PMID:209568", "title": "Erythrocytosis in hepatocellular cancer.", "content": "A Black patient with hepatocellular cancer and an increased red cell mass (erythrocytosis) is described. Assay of the patient's serum in ex-hypoxic polycythaemic mice showed the presence of erythropoietic activity. To determine the incidence of erythrocytosis in Southern African Blacks with hepatocellular cancer, haemoglobin and haematocrit values in 117 such patients were reviewed. Four patients (3,4%) had haemoglobin levels above the upper limit of normal and 2 (1,7%) of the patients had raised haematocrit values. Fifty-eight per cent of the patients were anaemic when they were first seen.", "contents": "Erythrocytosis in hepatocellular cancer. A Black patient with hepatocellular cancer and an increased red cell mass (erythrocytosis) is described. Assay of the patient's serum in ex-hypoxic polycythaemic mice showed the presence of erythropoietic activity. To determine the incidence of erythrocytosis in Southern African Blacks with hepatocellular cancer, haemoglobin and haematocrit values in 117 such patients were reviewed. Four patients (3,4%) had haemoglobin levels above the upper limit of normal and 2 (1,7%) of the patients had raised haematocrit values. Fifty-eight per cent of the patients were anaemic when they were first seen."}
{"id": "PMID:209572", "title": "The subcellular distribution of [3H]-colchicine-binding activity and tubulin in pig blood platelets.", "content": "The subcellular distribution of the [3H]-colchicine-binding protein, believed to be tubulin, the subunit protein of microtubules, has been investigated in mammalian blood platelets. Studies on a soluble extract from pig platelets and two particulate fractions (viz. membrane-rich and granule-rich fractions) have shown that about 98% of the colchicine-binding activity in a platelet homogenate is located in the soluble phase. This result is in agreement with polyacrylamide gel electrophoresis experiments which show that the soluble fraction contains a substantial amount of 55,000 MW tubulin, whereas the membrane and granule-rich fractions contain very little of this component. The [3H]-colchicine-binding activity of the platelet soluble phase is largely precipitated by 40-50% ammonium sulphate and also by vinblastine sulphate in millimolar concentrations. Moreover the colchicine-binding protein in the platelet soluble fraction has a sedimentation coefficient of 5.9 S, is eluted in the void volume of a Sephadex G-100 column, and binds to DEAE-Sephadex at low ionic strength and is eluted from this ion-exchanger at an ionic strength of 0.47 M-KCl. In addition, most of the colchicine-binding activity of the platelet soluble phase is associated with protein which will undergo temperature-dependent polymerization in vitro and which has a molecular weight on SDS-polyacrylamide gels of 55,000. All these experimental findings suggest that the colchicine-binding activity of pig platelet homogenates is due to the presence of the microtubule protein, tubulin, which is largely found in the soluble compartment of the cells.", "contents": "The subcellular distribution of [3H]-colchicine-binding activity and tubulin in pig blood platelets. The subcellular distribution of the [3H]-colchicine-binding protein, believed to be tubulin, the subunit protein of microtubules, has been investigated in mammalian blood platelets. Studies on a soluble extract from pig platelets and two particulate fractions (viz. membrane-rich and granule-rich fractions) have shown that about 98% of the colchicine-binding activity in a platelet homogenate is located in the soluble phase. This result is in agreement with polyacrylamide gel electrophoresis experiments which show that the soluble fraction contains a substantial amount of 55,000 MW tubulin, whereas the membrane and granule-rich fractions contain very little of this component. The [3H]-colchicine-binding activity of the platelet soluble phase is largely precipitated by 40-50% ammonium sulphate and also by vinblastine sulphate in millimolar concentrations. Moreover the colchicine-binding protein in the platelet soluble fraction has a sedimentation coefficient of 5.9 S, is eluted in the void volume of a Sephadex G-100 column, and binds to DEAE-Sephadex at low ionic strength and is eluted from this ion-exchanger at an ionic strength of 0.47 M-KCl. In addition, most of the colchicine-binding activity of the platelet soluble phase is associated with protein which will undergo temperature-dependent polymerization in vitro and which has a molecular weight on SDS-polyacrylamide gels of 55,000. All these experimental findings suggest that the colchicine-binding activity of pig platelet homogenates is due to the presence of the microtubule protein, tubulin, which is largely found in the soluble compartment of the cells."}
{"id": "PMID:209573", "title": "Effect on platelet functions of derivatives of cyclic nucleotides.", "content": "Derivatives of cyclic nucleotides were evaluated for their ability to inhibit platelet aggregation and the release reaction. Derivatives substituted in position 8 (mainly 8-Br-cyclic GMP) were more active than 3'-5' cyclic AMP, and their relative potency in inhibiting platelet aggregation and 14C-serotonin release was comparable to that of N62-0'-dibutyryl-cyclic AMP. Compounds substituted in position 6 or 2'-0 were not effective. The active compounds, which were also tested for their ability to stimulate platelet adenylate cyclase or to inhibit cyclic AMP phosphodiesterase, did not modify the intracellular levels of cyclic AMP. Since previous animal experiments have shown that these derivatives cause less side effects than cyclic AMP and its dibutyryl derivative in animals, it is suggested that modification of the cyclophosphate molecule might make it possible to find compounds active only on platelet function without interfering with other biological systems.", "contents": "Effect on platelet functions of derivatives of cyclic nucleotides. Derivatives of cyclic nucleotides were evaluated for their ability to inhibit platelet aggregation and the release reaction. Derivatives substituted in position 8 (mainly 8-Br-cyclic GMP) were more active than 3'-5' cyclic AMP, and their relative potency in inhibiting platelet aggregation and 14C-serotonin release was comparable to that of N62-0'-dibutyryl-cyclic AMP. Compounds substituted in position 6 or 2'-0 were not effective. The active compounds, which were also tested for their ability to stimulate platelet adenylate cyclase or to inhibit cyclic AMP phosphodiesterase, did not modify the intracellular levels of cyclic AMP. Since previous animal experiments have shown that these derivatives cause less side effects than cyclic AMP and its dibutyryl derivative in animals, it is suggested that modification of the cyclophosphate molecule might make it possible to find compounds active only on platelet function without interfering with other biological systems."}
{"id": "PMID:209575", "title": "Studies on bovine leucosis V. A comparative study on the practical value of the agar gel immunodiffusion test, the indirect fluorescent antibody technique and the micro complement fixation test for the detection of antibodies to bovine leucosis virus.", "content": "The practical value of the indirect fluorescent antibody technique (I FAT), the micro complement fixation test (M CFT) and the agar gel immunodiffusion test (AGIDT) for the detection of antibodies to bovine leucosis virus (BLV) was investigated. For this purpose 1495 serum samples were examined. There was a remarkably good agreement between the three tests in the demonstration of antibodies to BLV especially if sera with a sufficient high concentration of antibodies (\"late serum\") were under investigation. These positive sera were derived only from farms which exploited one or more imported animals. A disagreement of results of the three tests was observed in 38 (2.5%) cases. This was due to: (1) difficulties in reading of the test; (2) presumably by the demonstration of different classes of antibody and (3) the fact that in the AGIDT sera could be used undiluted. This discrepancy was especially evident with sera with a low concentration of antibodies (\"early or incubation sera\"). A drawback for the M CFT is the anticomplementary activity found in 17% of the bovine serum samples.", "contents": "Studies on bovine leucosis V. A comparative study on the practical value of the agar gel immunodiffusion test, the indirect fluorescent antibody technique and the micro complement fixation test for the detection of antibodies to bovine leucosis virus. The practical value of the indirect fluorescent antibody technique (I FAT), the micro complement fixation test (M CFT) and the agar gel immunodiffusion test (AGIDT) for the detection of antibodies to bovine leucosis virus (BLV) was investigated. For this purpose 1495 serum samples were examined. There was a remarkably good agreement between the three tests in the demonstration of antibodies to BLV especially if sera with a sufficient high concentration of antibodies (\"late serum\") were under investigation. These positive sera were derived only from farms which exploited one or more imported animals. A disagreement of results of the three tests was observed in 38 (2.5%) cases. This was due to: (1) difficulties in reading of the test; (2) presumably by the demonstration of different classes of antibody and (3) the fact that in the AGIDT sera could be used undiluted. This discrepancy was especially evident with sera with a low concentration of antibodies (\"early or incubation sera\"). A drawback for the M CFT is the anticomplementary activity found in 17% of the bovine serum samples."}
{"id": "PMID:209578", "title": "[Study of the biochemical and radiochemical effects of the agent MTDQ (author's transl].", "content": "The antioxidant MTDQ exhibits a radiosensitizing effect and was used in pretreatment of radiation-resistant human tumors, e.g. synoviomas, sarcomas, von Recklinghausen disease. After this premedication and fractionated radiation therapy of different kinds a permanent regression of the tumors was observed. The radiosensitizing compound is non-toxic and selectively accumulates in tumorous tissues. The chemical structure (three functional groups) and in vitro tests make probable that the main factors in the mechanism of action are peroxide decomposition, hydrol formation, polymerization and, in the course of those reactions, the in situ release of oxygen.", "contents": "[Study of the biochemical and radiochemical effects of the agent MTDQ (author's transl]. The antioxidant MTDQ exhibits a radiosensitizing effect and was used in pretreatment of radiation-resistant human tumors, e.g. synoviomas, sarcomas, von Recklinghausen disease. After this premedication and fractionated radiation therapy of different kinds a permanent regression of the tumors was observed. The radiosensitizing compound is non-toxic and selectively accumulates in tumorous tissues. The chemical structure (three functional groups) and in vitro tests make probable that the main factors in the mechanism of action are peroxide decomposition, hydrol formation, polymerization and, in the course of those reactions, the in situ release of oxygen."}
{"id": "PMID:209579", "title": "Chromatographic separation of vitamin D3 sulfate and vitamin D3.", "content": "This paper describes a simple chromatographic technique on Sephadex LH20 for the separation of vitamin D3 sulfate from free vitamin D3 and its metabolites. This technique has been used in the study of vitamin D3 sulfate metabolism in rats. Seven hours after injection of vitamin D3 sulfate (35S or 35S and 3H) only the peak of vitamin D sulfoconjugate was found in chromatographic elution of serum extracts.", "contents": "Chromatographic separation of vitamin D3 sulfate and vitamin D3. This paper describes a simple chromatographic technique on Sephadex LH20 for the separation of vitamin D3 sulfate from free vitamin D3 and its metabolites. This technique has been used in the study of vitamin D3 sulfate metabolism in rats. Seven hours after injection of vitamin D3 sulfate (35S or 35S and 3H) only the peak of vitamin D sulfoconjugate was found in chromatographic elution of serum extracts."}
{"id": "PMID:209580", "title": "[Etiology of chronic recurring aphthous stomatitis].", "content": "46 patients with chronic recurrent aphthae of the oral mucosa were subjected to clinical, virological and serologic examinations to evidence the assumed virus aetiology of this clinical picture. A cytopathogenic organism (classified as herpes virus hominis) could be cultivated from the aphtha sample from only one patient.", "contents": "[Etiology of chronic recurring aphthous stomatitis]. 46 patients with chronic recurrent aphthae of the oral mucosa were subjected to clinical, virological and serologic examinations to evidence the assumed virus aetiology of this clinical picture. A cytopathogenic organism (classified as herpes virus hominis) could be cultivated from the aphtha sample from only one patient."}
{"id": "PMID:209586", "title": "The control of endemic goitre by iodized oil in a community health programme.", "content": "A programme of iodized oil injections was carried out in an area of high goitre prevalence (28.5%) in rural Zaire. The iodized oil programme was undertaken as a part of a broader, pre-existing community health programme. No complications were encountered.", "contents": "The control of endemic goitre by iodized oil in a community health programme. A programme of iodized oil injections was carried out in an area of high goitre prevalence (28.5%) in rural Zaire. The iodized oil programme was undertaken as a part of a broader, pre-existing community health programme. No complications were encountered."}
{"id": "PMID:209581", "title": "Isoproterenol and propranolol: ability to cross the blood-brain barrier and effects on cerebral circulation in man.", "content": "Using the \"double indicator\" technique the ability of 3H-isoproterenol and 14C-propranolol to cross the blood-brain barrier was studied in man. In 3 subjects extraction of isoproterenol was 3.8% in a single passage and the PS product was 2.0 ml/100g/min. In 4 patients extraction of propranolol was 63% and PS was 46.7 ml/100/min. Regional cerebral blood flow (rCBF) was studied in man with the 133Xe-intraarterial injection method. Intracarotid isoproterenol (3 migrogram/min., 6 patients) caused a significant reduction in rCBF, but after correction for a concomitant decrease in arterial PCO2 the alteration was no longer significant (59.8 -51.7/57.4 ml/100g/min.). Intracarotid propranolol (0.15 mg/kg, 11 patients) caused no significant change in rCBF, but after correction for arterial PCO2 change the lateration although on 4% was just significant, p less than 0.05. (56.3 -55.8/54.1 ml/100g/min). After propranolol the rCBF changes caused by alterations in the arterial PCO2 were normal and the focal flow increase during hand work could not be changed by simultaneous intracarotid propranolol.", "contents": "Isoproterenol and propranolol: ability to cross the blood-brain barrier and effects on cerebral circulation in man. Using the \"double indicator\" technique the ability of 3H-isoproterenol and 14C-propranolol to cross the blood-brain barrier was studied in man. In 3 subjects extraction of isoproterenol was 3.8% in a single passage and the PS product was 2.0 ml/100g/min. In 4 patients extraction of propranolol was 63% and PS was 46.7 ml/100/min. Regional cerebral blood flow (rCBF) was studied in man with the 133Xe-intraarterial injection method. Intracarotid isoproterenol (3 migrogram/min., 6 patients) caused a significant reduction in rCBF, but after correction for a concomitant decrease in arterial PCO2 the alteration was no longer significant (59.8 -51.7/57.4 ml/100g/min.). Intracarotid propranolol (0.15 mg/kg, 11 patients) caused no significant change in rCBF, but after correction for arterial PCO2 change the lateration although on 4% was just significant, p less than 0.05. (56.3 -55.8/54.1 ml/100g/min). After propranolol the rCBF changes caused by alterations in the arterial PCO2 were normal and the focal flow increase during hand work could not be changed by simultaneous intracarotid propranolol."}
{"id": "PMID:209582", "title": "Alterations of cyclic AMP in cerebral ischemia.", "content": "Cyclic AMP levels were measured in brains of 21 cats after occlusion of a middle cerebral artery by a transorbital approach. Brain samples for determination of cAMP by a protein binding radioassay were obtained from the ischemic and contralateral temporal lobes before sacrifice, 1, 3, and 24 hours after occlusion of the right middle cerebral artery. At 1 hour, no difference between the 2 sides was observed; a mean of 17.4 pmoles/mg protein was observed from the side of the occlusion and 18.9 pmoles/mg protein from the contralateral side. At 3 hours, a mean value of 8.9 pmoles/mg protein on the ischemic side and a level of 21.7 pmoles/mg protein on the contralateral side were observed. At 24 hours, the cAMP level on the ischemic side remained below the nonischemic side; the values obtained were 13.7 pmoles/mg protein compared to 27.9 pmoles/mg protein compared to 27.9 pmoles/mg protein. These changes in cAMP as early as 3 hours after the onset of ischemia, when such a lesion is reversible, may indicate that in initial step in the alteration of cellular metabolism following ischemia is due to membrane perturbation and altered production of this second messenger.", "contents": "Alterations of cyclic AMP in cerebral ischemia. Cyclic AMP levels were measured in brains of 21 cats after occlusion of a middle cerebral artery by a transorbital approach. Brain samples for determination of cAMP by a protein binding radioassay were obtained from the ischemic and contralateral temporal lobes before sacrifice, 1, 3, and 24 hours after occlusion of the right middle cerebral artery. At 1 hour, no difference between the 2 sides was observed; a mean of 17.4 pmoles/mg protein was observed from the side of the occlusion and 18.9 pmoles/mg protein from the contralateral side. At 3 hours, a mean value of 8.9 pmoles/mg protein on the ischemic side and a level of 21.7 pmoles/mg protein on the contralateral side were observed. At 24 hours, the cAMP level on the ischemic side remained below the nonischemic side; the values obtained were 13.7 pmoles/mg protein compared to 27.9 pmoles/mg protein compared to 27.9 pmoles/mg protein. These changes in cAMP as early as 3 hours after the onset of ischemia, when such a lesion is reversible, may indicate that in initial step in the alteration of cellular metabolism following ischemia is due to membrane perturbation and altered production of this second messenger."}
{"id": "PMID:209590", "title": "Machakos project studies. Agents affecting health of mother and child in a rural area of Kenya. V. Pertussis sentypes in Kenyan children 1974--1975.", "content": "Cultures of Bordetella pertussis were isolated by pernasal swabs from Kenyan children in whom whooping-cough was suspected. Serotyping of 94 of these isolates was undertaken by four laboratories in Europe, and there was very close agreement in their typing results. Each laboratory found that the incidence of type 1, 3 was the lowest of the three types, and that there were approximately equal numbers of types 1, 2, 3 and 1, 2. No new serotype was found. This distribution of serotypes was found in all age-groups; and it is in marked contrast with that currently seen in vaccinated communities, where type 1, 3 predominates. The implications of these findings for vaccination against whooping-cough in East Africa are discussed.", "contents": "Machakos project studies. Agents affecting health of mother and child in a rural area of Kenya. V. Pertussis sentypes in Kenyan children 1974--1975. Cultures of Bordetella pertussis were isolated by pernasal swabs from Kenyan children in whom whooping-cough was suspected. Serotyping of 94 of these isolates was undertaken by four laboratories in Europe, and there was very close agreement in their typing results. Each laboratory found that the incidence of type 1, 3 was the lowest of the three types, and that there were approximately equal numbers of types 1, 2, 3 and 1, 2. No new serotype was found. This distribution of serotypes was found in all age-groups; and it is in marked contrast with that currently seen in vaccinated communities, where type 1, 3 predominates. The implications of these findings for vaccination against whooping-cough in East Africa are discussed."}
{"id": "PMID:209591", "title": "Serum albumin and total globulin levels in common liver diseases in Accra (Ghana).", "content": "Serum albumin and total globulin were determined in 22 healthy people, 29 patients with acute viral hepatitis, 27 patients with cirrhosis and 27 patients with primary hepatocellular carcinoma to see if they might be of discriminating value. The mean serum albumin values were found to be highest in the healthy subjects followed by acute viral hepatitis, primary hepatocellular carcinoma and cirrhosis, in that order. The mean serum total globulin values on the other hand, were found to be lowest in the healthy subjects followed by acute viral hepatitis, primary hepatocellular carcinoma and cirrhosis, in that order. Both the mean albumin and mean total globulin of each group of subjects were significantly different from the respective means of the other three groups. A probable explanation for the higher serum albumin and lower globulin levels found in primary hepatocellular carcinoma, as compared to cirrhosis, is that hepatocellular carcinoma occurs in reasonably well-compensated cases of cirrhosis.", "contents": "Serum albumin and total globulin levels in common liver diseases in Accra (Ghana). Serum albumin and total globulin were determined in 22 healthy people, 29 patients with acute viral hepatitis, 27 patients with cirrhosis and 27 patients with primary hepatocellular carcinoma to see if they might be of discriminating value. The mean serum albumin values were found to be highest in the healthy subjects followed by acute viral hepatitis, primary hepatocellular carcinoma and cirrhosis, in that order. The mean serum total globulin values on the other hand, were found to be lowest in the healthy subjects followed by acute viral hepatitis, primary hepatocellular carcinoma and cirrhosis, in that order. Both the mean albumin and mean total globulin of each group of subjects were significantly different from the respective means of the other three groups. A probable explanation for the higher serum albumin and lower globulin levels found in primary hepatocellular carcinoma, as compared to cirrhosis, is that hepatocellular carcinoma occurs in reasonably well-compensated cases of cirrhosis."}
{"id": "PMID:209592", "title": "Immunization of mice against Trypanosoma cruzi: the effect of chemical treatment or immune serum on an epimastigote vaccine.", "content": "Groups of long Evans and CD-1 mice were immunized with vaccines prepared from epimastigotes of Trypanosoma cruzi, strains Y and Tulahuen, modified by various chemical means, or by the addition of immune sera. Freeze-thawed epimastigotes were used as a control antigen. Freeze-thawed epimastigotes, with and without saponin as adjuvant, gave significant protection against challenge with homologous trypomastigotes. Similar levels or protection were obtained in mice vaccinated with living epimastigotes. Treatment of epimastigotes by various chemical means, including sodium perchlorate failed to increase their immunogenicity, but did not reduce it. The addition of immune serum to the antigen may have slightly increased its immunogenicity.", "contents": "Immunization of mice against Trypanosoma cruzi: the effect of chemical treatment or immune serum on an epimastigote vaccine. Groups of long Evans and CD-1 mice were immunized with vaccines prepared from epimastigotes of Trypanosoma cruzi, strains Y and Tulahuen, modified by various chemical means, or by the addition of immune sera. Freeze-thawed epimastigotes were used as a control antigen. Freeze-thawed epimastigotes, with and without saponin as adjuvant, gave significant protection against challenge with homologous trypomastigotes. Similar levels or protection were obtained in mice vaccinated with living epimastigotes. Treatment of epimastigotes by various chemical means, including sodium perchlorate failed to increase their immunogenicity, but did not reduce it. The addition of immune serum to the antigen may have slightly increased its immunogenicity."}
{"id": "PMID:209593", "title": "Bioactivity of male (sperm transmitted) mouse mammary tumor virus as influenced by donor, recipient and age at treatment.", "content": "The sperm collected from mammary tumor virus (MTV)-carrying mice (C3H, BALB/cfC3H, BALB/cfRIII and RIII) was separately tested for mammary tumor-inducing activity in (BALB/c x C3Hf)F1, (BALB/c x RIIIf) F1, and BALB/c female recipients by i.p., injection of 0.1 ml of the sperm at 1-2 weeks or at 3 months of age. A total of 551 recipents was observed, including control mice. The results may be summarized as follow: 1) mammary tumor incidence in experiments with or without histocompatibility between sperm donor and recipient is the same; 2) bioactivity is related to the type of MTV (C3H, RIII) and to the type of recipient, not to the sperm donor; 3) the activity of RIII MTV released in the sperm appears to be less influenced by the age of recipients than is that of C3H MTV; 4) BALB/c recipients are  more susceptible to C3H than to RIII sperm-released MTV; 5) (BALB/c x RIIIf) F1 hybrids are resistant to sperm-released MTV, especially to C3H MTV infection, and show a 34% incidence of late spontneous lymphomas inherited by the RIIf male parent; 6) (BALB/c x C3Hf) F1 hybrids  are susceptible to both C3H and RIII sperm-released MTV and show a 30% incidence of late spontaneous mammary tumors due to genetic transmission of MTV by the C3H male parent.", "contents": "Bioactivity of male (sperm transmitted) mouse mammary tumor virus as influenced by donor, recipient and age at treatment. The sperm collected from mammary tumor virus (MTV)-carrying mice (C3H, BALB/cfC3H, BALB/cfRIII and RIII) was separately tested for mammary tumor-inducing activity in (BALB/c x C3Hf)F1, (BALB/c x RIIIf) F1, and BALB/c female recipients by i.p., injection of 0.1 ml of the sperm at 1-2 weeks or at 3 months of age. A total of 551 recipents was observed, including control mice. The results may be summarized as follow: 1) mammary tumor incidence in experiments with or without histocompatibility between sperm donor and recipient is the same; 2) bioactivity is related to the type of MTV (C3H, RIII) and to the type of recipient, not to the sperm donor; 3) the activity of RIII MTV released in the sperm appears to be less influenced by the age of recipients than is that of C3H MTV; 4) BALB/c recipients are  more susceptible to C3H than to RIII sperm-released MTV; 5) (BALB/c x RIIIf) F1 hybrids are resistant to sperm-released MTV, especially to C3H MTV infection, and show a 34% incidence of late spontneous lymphomas inherited by the RIIf male parent; 6) (BALB/c x C3Hf) F1 hybrids  are susceptible to both C3H and RIII sperm-released MTV and show a 30% incidence of late spontaneous mammary tumors due to genetic transmission of MTV by the C3H male parent."}
{"id": "PMID:209594", "title": "Analysis of frog neuromuscular function at hyperbaric pressures.", "content": "Nerve and muscle compound action potentials were measured in the frog sciatic nerve-gastrocnemius muscle preparation in a hyperbaric helium-air environment. Helium pressure to 69 ATA induced a reversible depression in muscle compound action potential amplitude without significantly affecting other parameters. Blockade other parameters. Blockade induced by tetraethylammonium while at pressure could be partially reversed by decompression. A desensitization-type of neuromuscular block produced at pressure after neostigmine infusion could also be partially reversed by decompression. These results suggest a possible involvement of the acetylcholine receptor complex in pressure-induced depression of synaptic transmission.", "contents": "Analysis of frog neuromuscular function at hyperbaric pressures. Nerve and muscle compound action potentials were measured in the frog sciatic nerve-gastrocnemius muscle preparation in a hyperbaric helium-air environment. Helium pressure to 69 ATA induced a reversible depression in muscle compound action potential amplitude without significantly affecting other parameters. Blockade other parameters. Blockade induced by tetraethylammonium while at pressure could be partially reversed by decompression. A desensitization-type of neuromuscular block produced at pressure after neostigmine infusion could also be partially reversed by decompression. These results suggest a possible involvement of the acetylcholine receptor complex in pressure-induced depression of synaptic transmission."}
{"id": "PMID:209595", "title": "Hypercalciuria related to cadmium exposure.", "content": "A work force has been investigated for possible cadmium intoxication. One group who are coppersmiths have an 18.5 per cent prevalence of upper urinary tract stone disease associated with a statistically highly significant hypercalciuria and reduced serum inorganic phosphate. Proof of exposure to cadmium has been confirmed in all workers. The trace element cadmium should be kept in mind when investigating stone formers who exhibit an unexplained hypercalciuria.", "contents": "Hypercalciuria related to cadmium exposure. A work force has been investigated for possible cadmium intoxication. One group who are coppersmiths have an 18.5 per cent prevalence of upper urinary tract stone disease associated with a statistically highly significant hypercalciuria and reduced serum inorganic phosphate. Proof of exposure to cadmium has been confirmed in all workers. The trace element cadmium should be kept in mind when investigating stone formers who exhibit an unexplained hypercalciuria."}
{"id": "PMID:209596", "title": "Anatomic effect of distention therapy in unstable bladder: new approach.", "content": "The recent clinical success of distention therapy in the treatment of the unstable bladder is reviewed. Bladder stability and increased capacity as measured by cystometry following distention therapy as well as relief of symptoms have prompted this anatomic study. The neuromuscular pathways of conduction in rat and rabbit bladder wall were examined following short-term (two-hour) and prolonged (six-hour) distention. Treated and control animals were studied at fixed intervals for four months. Prolonged distention did not alter either smooth muscle cell architecture or intercellular junctions. It did produce a transient phase of degeneration among the unmyelinated nerve fibers in the bladder wall consisting of axonal swelling and lysis of organelles. A quantitative estimate of nerve injury was compiled using pooled histograms. These results suggest that bladder stability following distention therapy may be related to nerve degeneration in the bladder wall.", "contents": "Anatomic effect of distention therapy in unstable bladder: new approach. The recent clinical success of distention therapy in the treatment of the unstable bladder is reviewed. Bladder stability and increased capacity as measured by cystometry following distention therapy as well as relief of symptoms have prompted this anatomic study. The neuromuscular pathways of conduction in rat and rabbit bladder wall were examined following short-term (two-hour) and prolonged (six-hour) distention. Treated and control animals were studied at fixed intervals for four months. Prolonged distention did not alter either smooth muscle cell architecture or intercellular junctions. It did produce a transient phase of degeneration among the unmyelinated nerve fibers in the bladder wall consisting of axonal swelling and lysis of organelles. A quantitative estimate of nerve injury was compiled using pooled histograms. These results suggest that bladder stability following distention therapy may be related to nerve degeneration in the bladder wall."}
{"id": "PMID:209597", "title": "Value of liver scintiscan in staging of testicular neoplasm.", "content": "A nineteen-year retrospective study of the usefulness of liver scanning in the staging evaluation of germinal cell testicular neoplasms was undertaken at the National Naval Medical Center. Of 94 patients, 90 (96 per cent) demonstrated accurate correlation between liver scan and histopathologic diagnosis.", "contents": "Value of liver scintiscan in staging of testicular neoplasm. A nineteen-year retrospective study of the usefulness of liver scanning in the staging evaluation of germinal cell testicular neoplasms was undertaken at the National Naval Medical Center. Of 94 patients, 90 (96 per cent) demonstrated accurate correlation between liver scan and histopathologic diagnosis."}
{"id": "PMID:209598", "title": "Adrenal autotransplantation.", "content": "New tools for the diagnosis of adrenal diseases and the development of successful techniques to treat patients with bilateral tumors of the kidney have increased the number of procedures involving removal of both adrenals. Offering to these patients an adrenal autograft represents more than a superfluous medical exercise, since a successful outcome of the graft will relieve them of the burdens and risks of long-term postoperative steroid replacement therapy. The aim of this review is to bring to mind the possibility of autografting adrenal glands in some clinical situations and to emphasize some points that could be relevant in obtaining successful results. The available data justify clinical trials with the procedure.", "contents": "Adrenal autotransplantation. New tools for the diagnosis of adrenal diseases and the development of successful techniques to treat patients with bilateral tumors of the kidney have increased the number of procedures involving removal of both adrenals. Offering to these patients an adrenal autograft represents more than a superfluous medical exercise, since a successful outcome of the graft will relieve them of the burdens and risks of long-term postoperative steroid replacement therapy. The aim of this review is to bring to mind the possibility of autografting adrenal glands in some clinical situations and to emphasize some points that could be relevant in obtaining successful results. The available data justify clinical trials with the procedure."}
{"id": "PMID:209600", "title": "[Laparoscopic diagnosis of glomus tumors].", "content": "3 cases of glomus tumors of the stomach, small bowel and lesser omentum were examined. In one patient the tumor was manifested through intraabdominal hemorrhage, diagnosed during laparoscopy; but the source of the hemorrhage remained unrecognized. The puncture of the tumor, which proved its benign character, was performed in the second case. The biopsy taken at the laparoscopy in the third patient showed angioleiomyosarcoma. All the patients were operated.", "contents": "[Laparoscopic diagnosis of glomus tumors]. 3 cases of glomus tumors of the stomach, small bowel and lesser omentum were examined. In one patient the tumor was manifested through intraabdominal hemorrhage, diagnosed during laparoscopy; but the source of the hemorrhage remained unrecognized. The puncture of the tumor, which proved its benign character, was performed in the second case. The biopsy taken at the laparoscopy in the third patient showed angioleiomyosarcoma. All the patients were operated."}
{"id": "PMID:209603", "title": "[Testing the immunogenicity of the dermal antigen in Marek's disease virus].", "content": "An experiment was performed to study the immunogenicity of the dermal antigen of Marek's disease virus, extracted from the skin of 30-day-old chickens, infected with Marek's disease virus on the first day of life. Three kinds of samples were tested: (1) dermal antigen centrifuged at 10 000 g per 0.5 h, (2) dermal antigen centrifugated at 10 000 g per 0.5 h and 100 000 g per 1 h, (3) dermal antigen treated like sample (2) and partly purified by DEAE-cellulose chromatography. Samples (1) and (2) were inoculated to two-day-old chickens and the vaccination was repeated, using complete Freund's adjuvant, 21 days later. Sample (3) was inoculated to two-day-old chickens with DEAE-dextran. All the three groups were challenged together with the controls (non-vaccinated chickens) on the seventh day after the first vaccination. A reduction of mortality was observed in the chickens vaccinated with and re-vaccinated with sample (1) (23.07%) and in the chickens vaccinated with sample (3) (30.76%). The chickens of the latter group were the last to start dying from Marek's disease--only after the 10th week of life. In the chickens which had been vaccinated and revaccinated with sample (2) the mortality was not reduced. The study is continued, with particular emphasis on the relationship of DEAE-dextran to protection against Marek's disease.", "contents": "[Testing the immunogenicity of the dermal antigen in Marek's disease virus]. An experiment was performed to study the immunogenicity of the dermal antigen of Marek's disease virus, extracted from the skin of 30-day-old chickens, infected with Marek's disease virus on the first day of life. Three kinds of samples were tested: (1) dermal antigen centrifuged at 10 000 g per 0.5 h, (2) dermal antigen centrifugated at 10 000 g per 0.5 h and 100 000 g per 1 h, (3) dermal antigen treated like sample (2) and partly purified by DEAE-cellulose chromatography. Samples (1) and (2) were inoculated to two-day-old chickens and the vaccination was repeated, using complete Freund's adjuvant, 21 days later. Sample (3) was inoculated to two-day-old chickens with DEAE-dextran. All the three groups were challenged together with the controls (non-vaccinated chickens) on the seventh day after the first vaccination. A reduction of mortality was observed in the chickens vaccinated with and re-vaccinated with sample (1) (23.07%) and in the chickens vaccinated with sample (3) (30.76%). The chickens of the latter group were the last to start dying from Marek's disease--only after the 10th week of life. In the chickens which had been vaccinated and revaccinated with sample (2) the mortality was not reduced. The study is continued, with particular emphasis on the relationship of DEAE-dextran to protection against Marek's disease."}
{"id": "PMID:209608", "title": "Feminizing adrenocortical tumor. Histological and ultrastructural study.", "content": "A case of a feminizing adrenocortical tumor associated with Cushing's syndrome in a 29 year old male is presented. The ultrastructural features are compared with adrenal tumors secreting aldosterone, glucocorticoids of androgens. As in adrenal carcinomas, this tumor demonstrates nuclear pleomorphism with enlarged nucleoli and nuclear pseudoinclusions. The cytoplasmic organelles show some parallels between feminizing and androgen-secreting adrenal tumors. Different types of mitochondria occur with varying amounts of smooth endoplasmic reticulum. Numerous microbodies are present. Histological and ultrastructural signs indicating probably malignancy are discussed and it is noted that most of the feminizing adrenal tumors are carcinomata. Neither local recurrence nor distant metastases have yet been detected in this case, two years after excision of the tumor.", "contents": "Feminizing adrenocortical tumor. Histological and ultrastructural study. A case of a feminizing adrenocortical tumor associated with Cushing's syndrome in a 29 year old male is presented. The ultrastructural features are compared with adrenal tumors secreting aldosterone, glucocorticoids of androgens. As in adrenal carcinomas, this tumor demonstrates nuclear pleomorphism with enlarged nucleoli and nuclear pseudoinclusions. The cytoplasmic organelles show some parallels between feminizing and androgen-secreting adrenal tumors. Different types of mitochondria occur with varying amounts of smooth endoplasmic reticulum. Numerous microbodies are present. Histological and ultrastructural signs indicating probably malignancy are discussed and it is noted that most of the feminizing adrenal tumors are carcinomata. Neither local recurrence nor distant metastases have yet been detected in this case, two years after excision of the tumor."}
{"id": "PMID:209609", "title": "Spheroidal filamentous inclusion body cells in von Recklinghausen's disease.", "content": "Cells with spheroidal filamentous cytoplasmic bodies, distinctive by both light and electron microscopy, were found in a neoplasm arising from the sciatic nerve of a patient with von Recklinghausen's disease. Tissue fixed with formalin and embedded in paraffin for three years was deparaffinized, reprocessed, and examined with the electron microscope. The morphology of the spheroidal body cells, the close resemblance to erythrophagocytosis, and the possible significance of the changes are discussed.", "contents": "Spheroidal filamentous inclusion body cells in von Recklinghausen's disease. Cells with spheroidal filamentous cytoplasmic bodies, distinctive by both light and electron microscopy, were found in a neoplasm arising from the sciatic nerve of a patient with von Recklinghausen's disease. Tissue fixed with formalin and embedded in paraffin for three years was deparaffinized, reprocessed, and examined with the electron microscope. The morphology of the spheroidal body cells, the close resemblance to erythrophagocytosis, and the possible significance of the changes are discussed."}
{"id": "PMID:209610", "title": "B-cell nature malignant lymphoma probably caused by EB-virus infection.", "content": "In cells in a haemopericardium associated with a B-cell malignant lymphoma, immature herpes type virus particles were found by electron microscopy. Epstein-Barr virus associated nuclear antigen (EBNA) and virus capsid antigen (VCA) were also found, both in the tumor cells, in the bloody pericardial fluid and in cultivated cells. Serological studies revealed high anti-toxoplasma antibody levels both in the pericardial fluid and in serum. Both EB virus and toxoplasma infections are assumed to have played an important role on the pathogenesis of the present case.", "contents": "B-cell nature malignant lymphoma probably caused by EB-virus infection. In cells in a haemopericardium associated with a B-cell malignant lymphoma, immature herpes type virus particles were found by electron microscopy. Epstein-Barr virus associated nuclear antigen (EBNA) and virus capsid antigen (VCA) were also found, both in the tumor cells, in the bloody pericardial fluid and in cultivated cells. Serological studies revealed high anti-toxoplasma antibody levels both in the pericardial fluid and in serum. Both EB virus and toxoplasma infections are assumed to have played an important role on the pathogenesis of the present case."}
{"id": "PMID:209612", "title": "Tumour cell interactions in vitro. Evidence for the occurrence of tumour cells within other tumour cells.", "content": "After addition of dibutyryl cAMP to spinner flask cultures of JB-1-E tumour cells an increase in the number of examples of emperipolesis was observed. Ruthenium red staining of the cells revealed a conspicuous staining of the cell membrane of the outer cell, while that of the inner cell was unstained. The differences in staining properties of the cell membranes of the outer and inner cells involved in emperipolesis and apparently viable inner cells make it evident that coexistence of cells--one within another--is possible.", "contents": "Tumour cell interactions in vitro. Evidence for the occurrence of tumour cells within other tumour cells. After addition of dibutyryl cAMP to spinner flask cultures of JB-1-E tumour cells an increase in the number of examples of emperipolesis was observed. Ruthenium red staining of the cells revealed a conspicuous staining of the cell membrane of the outer cell, while that of the inner cell was unstained. The differences in staining properties of the cell membranes of the outer and inner cells involved in emperipolesis and apparently viable inner cells make it evident that coexistence of cells--one within another--is possible."}
{"id": "PMID:209613", "title": "Investigations on the presence of antibodies to alphaviruses, flaviviruses, Bunyavirus and Kemerovo virus in humans and some domestic animals.", "content": "The presence of antibodies to some alphaviruses, flaviviruses, bunyaviruses and orbiviruses was studied in the sera from humans and domestic animals of biotopes \"C\" and \"T\" in the south-east of Romania. Specific antibodies were found in humans to 3 alphaviruses (eastern equine encephalitis, western equine encephalitis and Sindbis), in a very low proportion, and to 3 flaviviruses (tickborne encephalitis, West Nile and Ntaya), at a much higher percentage. Very low percentages of antibodies to Bunyavirus and Kemerovo virus were also detected. The proportion of antibodies to flaviruses (tick-borne encephalitis, West Nile and Ntaya) detected in domestic animals (sheep, cattle and swine) is much lower than that found in humans of the same biotope (\"T\").", "contents": "Investigations on the presence of antibodies to alphaviruses, flaviviruses, Bunyavirus and Kemerovo virus in humans and some domestic animals. The presence of antibodies to some alphaviruses, flaviviruses, bunyaviruses and orbiviruses was studied in the sera from humans and domestic animals of biotopes \"C\" and \"T\" in the south-east of Romania. Specific antibodies were found in humans to 3 alphaviruses (eastern equine encephalitis, western equine encephalitis and Sindbis), in a very low proportion, and to 3 flaviviruses (tickborne encephalitis, West Nile and Ntaya), at a much higher percentage. Very low percentages of antibodies to Bunyavirus and Kemerovo virus were also detected. The proportion of antibodies to flaviruses (tick-borne encephalitis, West Nile and Ntaya) detected in domestic animals (sheep, cattle and swine) is much lower than that found in humans of the same biotope (\"T\")."}
{"id": "PMID:209614", "title": "Isoenzymes of lactate dehydrogenase, acid phosphatase, alkaline phosphatase and peroxidase in monkey kidney cell cultures inoculated with herpes virus type 1.", "content": "The variation of lactate dehydrogenase, peroxidase, acid and alkaline phosphatase isoenzymes was studied in VERO cells inoculated with infectant and UV-inactivated herpes simplex virus type 1 (HSV--1). Infectant HSV--1 induced quantitative and qualitative modifications in isoenzyme patterns within the first 4 hours post inoculation (p.i.). The modifications caused by the UV-inactivated HSV--1 were similar, but appeared 8 hours p.i. The possibility of using isoenzyme modifications as rapid, sensitive and specific biochemical tests for virus detection and differentiation between infectant and inactivated virus is discussed.", "contents": "Isoenzymes of lactate dehydrogenase, acid phosphatase, alkaline phosphatase and peroxidase in monkey kidney cell cultures inoculated with herpes virus type 1. The variation of lactate dehydrogenase, peroxidase, acid and alkaline phosphatase isoenzymes was studied in VERO cells inoculated with infectant and UV-inactivated herpes simplex virus type 1 (HSV--1). Infectant HSV--1 induced quantitative and qualitative modifications in isoenzyme patterns within the first 4 hours post inoculation (p.i.). The modifications caused by the UV-inactivated HSV--1 were similar, but appeared 8 hours p.i. The possibility of using isoenzyme modifications as rapid, sensitive and specific biochemical tests for virus detection and differentiation between infectant and inactivated virus is discussed."}
{"id": "PMID:209615", "title": "Immunoelectrophoretic study of the host antigens of Sendai virus cultivated in different substrates (embryonated hen eggs and KB cells). Note I. Analysis of chorioallantoic membrane host antigens.", "content": "The immunoelectrophhoretic analysis of two preparations of the same virus cultivated in different substrates (Sendai/egg and Sendai/KB) demonstrate that virus envelopes contain: a) identical virus-specific antigens (but also some virus antigens with only partial immunochemical identity, or even non-identity); b) antigens incorporated by the virus from the host cell, during assembly and release. The latter differ according to the host, and some of them are only partially identical with the corresponding antigens of the host cell, which suggests that host cell glycoproteins are incorporated into the virus envelope after certain virus-induced modifications.", "contents": "Immunoelectrophoretic study of the host antigens of Sendai virus cultivated in different substrates (embryonated hen eggs and KB cells). Note I. Analysis of chorioallantoic membrane host antigens. The immunoelectrophhoretic analysis of two preparations of the same virus cultivated in different substrates (Sendai/egg and Sendai/KB) demonstrate that virus envelopes contain: a) identical virus-specific antigens (but also some virus antigens with only partial immunochemical identity, or even non-identity); b) antigens incorporated by the virus from the host cell, during assembly and release. The latter differ according to the host, and some of them are only partially identical with the corresponding antigens of the host cell, which suggests that host cell glycoproteins are incorporated into the virus envelope after certain virus-induced modifications."}
{"id": "PMID:209616", "title": "Effects and mechanism of the interaction between ceruloplasmin and some viruses or subviral components.", "content": "The results of investigations concerning the interaction between ceruloplasmin (a serum nonspecific inhibitor) and some myxo- and paramyxoviruses, as well as certain viruses with oncogenic potential (herpes virus, SV--40) are reviewed. The data presented point out the inhibiting action of ceruloplasmin on virus multiplication and the ceruloplasmin-induced modification in the antigenicity of Sendai virus and subviral fractions. The stages and mechanisms of ceruloplasmin action are discussed.", "contents": "Effects and mechanism of the interaction between ceruloplasmin and some viruses or subviral components. The results of investigations concerning the interaction between ceruloplasmin (a serum nonspecific inhibitor) and some myxo- and paramyxoviruses, as well as certain viruses with oncogenic potential (herpes virus, SV--40) are reviewed. The data presented point out the inhibiting action of ceruloplasmin on virus multiplication and the ceruloplasmin-induced modification in the antigenicity of Sendai virus and subviral fractions. The stages and mechanisms of ceruloplasmin action are discussed."}
{"id": "PMID:209628", "title": "[Differential diagnosis of glomus and glomal stomach tumors].", "content": "Two cases of glomangiomas of the stomach are described in detail. Moreover 8 cases of mixed glomus tumors of the stomach were clinically observed, one of them being previously described. The analysis of clinico-radiological and morphological features of these diseases, based both on the personal authors' and literature material enabled the conclusion to be drawn on the presence of a number of signs, which could contribute to differentiating between glomangiomas (Barre-Masson tumors) and  epitheliod leiomyomas of the stomach. These differences may be of some practical value in selecting the therapeutic tactics and formulating the prognosis.", "contents": "[Differential diagnosis of glomus and glomal stomach tumors]. Two cases of glomangiomas of the stomach are described in detail. Moreover 8 cases of mixed glomus tumors of the stomach were clinically observed, one of them being previously described. The analysis of clinico-radiological and morphological features of these diseases, based both on the personal authors' and literature material enabled the conclusion to be drawn on the presence of a number of signs, which could contribute to differentiating between glomangiomas (Barre-Masson tumors) and  epitheliod leiomyomas of the stomach. These differences may be of some practical value in selecting the therapeutic tactics and formulating the prognosis."}
{"id": "PMID:209634", "title": "[Angiography in abdominal diseases (author's transl)].", "content": "Angiography of arteries and veins in the abdominal and retroperitoneal compartement is a valuable routine roentgenologic procedure. Its value in the diagnosis of vascular disorders is apparent. Regarding space occupying lesions in the abdomen angiography is an aid in diagnosis and differential diagnosis and provides information on the curability. Visualization of the venous system will give mainly information on the extent of a tumor. For an evaluation of portal hypertension the arterial indirect visualization of the portal venous system is superior to the direct percutaneous splenoportography. In the acute gastrointestinal bleeding selective angiography is able to demonstrate the bleeding site.", "contents": "[Angiography in abdominal diseases (author's transl)]. Angiography of arteries and veins in the abdominal and retroperitoneal compartement is a valuable routine roentgenologic procedure. Its value in the diagnosis of vascular disorders is apparent. Regarding space occupying lesions in the abdomen angiography is an aid in diagnosis and differential diagnosis and provides information on the curability. Visualization of the venous system will give mainly information on the extent of a tumor. For an evaluation of portal hypertension the arterial indirect visualization of the portal venous system is superior to the direct percutaneous splenoportography. In the acute gastrointestinal bleeding selective angiography is able to demonstrate the bleeding site."}
{"id": "PMID:209630", "title": "Recent advances in the understanding of acupuncture.", "content": "The controversy about acupuncture is familiar to us since its recent reintroduction into this country. Much of its philosophical concepts were taken at their face values as the bases for condemnation. Since I last reviewed these antiquated concepts in the light of modern medicine, much has developed. It seems that if the effects of acupuncture were transmitted along the peripheral nerves to the central nervous system, it would be more effective if applied segmentally to the site of noxious stimulation. Disruption of extralamniscal pathways would abolish its analgesic effect. The distant and nonsegmentally located acupuncture points exert their influences through the integrative efforts of the reticular formation and the thalamus. The demonstration of transmissibility of acupuncture analgesia through blood and cerebrospinal fluid in animals implicates the involvement of humoral factors. Since such an effect can be suppressed by naloxone or by hypophysectomy, endorphins are thought to be involved. Such laboratory evidences indeed begin to shed some light on a possible neurohumoral mechanism of acupuncture. The differences between acupuncture and hypnosis are discussed. Acupuncture points were compared with referred pain, trigger points and motor points of the skeletal muscles. Its possible uses for other than pain, such as drug addiction, alcoholism, etc. are also reviewed.", "contents": "Recent advances in the understanding of acupuncture. The controversy about acupuncture is familiar to us since its recent reintroduction into this country. Much of its philosophical concepts were taken at their face values as the bases for condemnation. Since I last reviewed these antiquated concepts in the light of modern medicine, much has developed. It seems that if the effects of acupuncture were transmitted along the peripheral nerves to the central nervous system, it would be more effective if applied segmentally to the site of noxious stimulation. Disruption of extralamniscal pathways would abolish its analgesic effect. The distant and nonsegmentally located acupuncture points exert their influences through the integrative efforts of the reticular formation and the thalamus. The demonstration of transmissibility of acupuncture analgesia through blood and cerebrospinal fluid in animals implicates the involvement of humoral factors. Since such an effect can be suppressed by naloxone or by hypophysectomy, endorphins are thought to be involved. Such laboratory evidences indeed begin to shed some light on a possible neurohumoral mechanism of acupuncture. The differences between acupuncture and hypnosis are discussed. Acupuncture points were compared with referred pain, trigger points and motor points of the skeletal muscles. Its possible uses for other than pain, such as drug addiction, alcoholism, etc. are also reviewed."}
{"id": "PMID:209643", "title": "[The appearance of pathognostic inclusion bodies in verruca vulgaris (author's transl)].", "content": "Pathognostic inclusion bodies develop in the nucleus. They frequently occur in the upper layers of the pathologically changed stratum spinosum. They are stained in an amphophilic or basophilic manner. Their structure is a nearly homogenous, finely grained or plaquelike one. The inclusion bodies contain masses of human wart viruses in a cristalline-like arrangement or are irregularily distributed. Feulgen staining is positive. Different pictures of inclusion bodies are demonstrated in paraffin sections. The knowledge of structural variants is very helpful in biopsy diagnosis of veruca vulgaris.", "contents": "[The appearance of pathognostic inclusion bodies in verruca vulgaris (author's transl)]. Pathognostic inclusion bodies develop in the nucleus. They frequently occur in the upper layers of the pathologically changed stratum spinosum. They are stained in an amphophilic or basophilic manner. Their structure is a nearly homogenous, finely grained or plaquelike one. The inclusion bodies contain masses of human wart viruses in a cristalline-like arrangement or are irregularily distributed. Feulgen staining is positive. Different pictures of inclusion bodies are demonstrated in paraffin sections. The knowledge of structural variants is very helpful in biopsy diagnosis of veruca vulgaris."}
{"id": "PMID:209640", "title": "[Functional organization of monosynaptic interneuronal connections in the cerebral cortex].", "content": "A study of monosynaptic intraneuronal connections was performed in micro-regions of sensorimotor and autitory cortical areas in cats. Certain definite characteristics were found in the joint activity of neurones which persisted after the regime of microsystem activity was changed. Neurones with a lower spike amplitude discharge earlier and elicite discharges in neurones with a greater spike amplitude; feed-backs are inhibitory. It is suggested that in both cortical areas there exist microsystems with similar organization composed of different types of neurones.", "contents": "[Functional organization of monosynaptic interneuronal connections in the cerebral cortex]. A study of monosynaptic intraneuronal connections was performed in micro-regions of sensorimotor and autitory cortical areas in cats. Certain definite characteristics were found in the joint activity of neurones which persisted after the regime of microsystem activity was changed. Neurones with a lower spike amplitude discharge earlier and elicite discharges in neurones with a greater spike amplitude; feed-backs are inhibitory. It is suggested that in both cortical areas there exist microsystems with similar organization composed of different types of neurones."}
{"id": "PMID:209644", "title": "[Critical remarks on the surgical treatment of syndactylia (author's transl)].", "content": "The technique of surgery for syndactylia is described in detail. The author's opinion about the optimal age for surgical correction of equally or unequally long fingers is reported. The importance of early intervention in case of complicated syndactylia is stressed. Until growth has come to an end, continuous follow-up is necessary for early recognizing late contractures.", "contents": "[Critical remarks on the surgical treatment of syndactylia (author's transl)]. The technique of surgery for syndactylia is described in detail. The author's opinion about the optimal age for surgical correction of equally or unequally long fingers is reported. The importance of early intervention in case of complicated syndactylia is stressed. Until growth has come to an end, continuous follow-up is necessary for early recognizing late contractures."}
{"id": "PMID:209647", "title": "[Antigenic activity of Bordetella pertussis during cultivation in liquid nutrient media].", "content": "The authors studied the antigenic activity of Bordetella pertussis during stab cultivation. For the first time there were revealed changes (oscillations) of antigenic activity: formation of 3 peaks of which the middle was the highest. A possibility of improving the quality of pertussis vaccine by using biomass at the height of the peak was experimentally founded.", "contents": "[Antigenic activity of Bordetella pertussis during cultivation in liquid nutrient media]. The authors studied the antigenic activity of Bordetella pertussis during stab cultivation. For the first time there were revealed changes (oscillations) of antigenic activity: formation of 3 peaks of which the middle was the highest. A possibility of improving the quality of pertussis vaccine by using biomass at the height of the peak was experimentally founded."}
{"id": "PMID:209651", "title": "Acute influence of LH and FSH on cyclic AMP formation in isolated granulosa cells of the rat.", "content": "A technique for the mechanical isolation of granulosa cells from the rat ovary is described. Cyclic AMP formation by the isolated granulosa cells of the follicles in various stages of development was studied in response to the administration in vitro of gonadotrophins. In granulosa cells from small to medium-sized follicles FSH but no LH stimulated cAMP formation, while in cells from pre-ovulatory follicles both gonadotrophins had a stimulatory effect. The effects of both gonadotrophins were transient with a maximal response after 15 to 60 min of incubation. In the presence of the phosphodiesterase inhibitor, 3-isobutyl-methylxanthine, the action of FSH was potentiated and prolonged while the response to LH was unaffected. These data indicate that both gonadotrophins activate the adenylate cyclase system of the isolated granulosa cells while FSH in addition stimulates the phosphodiesterase activity. Consecutive determinations of cAMP during and after the pre-ovulatory LH-FSH surge, demonstrated a rise of cAMP levels in granulosa cells from the pre-ovulatory follicles following endogenous gonadotrophin release. cAMP levels remained high or increased until the time of ovulation.", "contents": "Acute influence of LH and FSH on cyclic AMP formation in isolated granulosa cells of the rat. A technique for the mechanical isolation of granulosa cells from the rat ovary is described. Cyclic AMP formation by the isolated granulosa cells of the follicles in various stages of development was studied in response to the administration in vitro of gonadotrophins. In granulosa cells from small to medium-sized follicles FSH but no LH stimulated cAMP formation, while in cells from pre-ovulatory follicles both gonadotrophins had a stimulatory effect. The effects of both gonadotrophins were transient with a maximal response after 15 to 60 min of incubation. In the presence of the phosphodiesterase inhibitor, 3-isobutyl-methylxanthine, the action of FSH was potentiated and prolonged while the response to LH was unaffected. These data indicate that both gonadotrophins activate the adenylate cyclase system of the isolated granulosa cells while FSH in addition stimulates the phosphodiesterase activity. Consecutive determinations of cAMP during and after the pre-ovulatory LH-FSH surge, demonstrated a rise of cAMP levels in granulosa cells from the pre-ovulatory follicles following endogenous gonadotrophin release. cAMP levels remained high or increased until the time of ovulation."}
{"id": "PMID:209652", "title": "Histochemical and histoenzymatic changes in mouse liver in subacute benzene intoxication.", "content": "The investigations were performed on mice. They were divided into a control group and 4 experimental groups. The experimental animals were administered intraperitoneally benzene 6 X every 24 h. The animals were decapitated 30 min. 4, 12 and 24 h after the last benzene administration. During the experiment, dyeing for neutral lipids and glycogen was carried out, and the activity of NADH2-r.t., SDH, G-6-Pase, ATP-ase and ACP was estimated. A decrease of glycogen content in liver cells, deviations in the amount of neutral lipids, reversible decrease of mitochondrial enzymes activity, and intensification of the processes of intracellular catabolism were found.", "contents": "Histochemical and histoenzymatic changes in mouse liver in subacute benzene intoxication. The investigations were performed on mice. They were divided into a control group and 4 experimental groups. The experimental animals were administered intraperitoneally benzene 6 X every 24 h. The animals were decapitated 30 min. 4, 12 and 24 h after the last benzene administration. During the experiment, dyeing for neutral lipids and glycogen was carried out, and the activity of NADH2-r.t., SDH, G-6-Pase, ATP-ase and ACP was estimated. A decrease of glycogen content in liver cells, deviations in the amount of neutral lipids, reversible decrease of mitochondrial enzymes activity, and intensification of the processes of intracellular catabolism were found."}
{"id": "PMID:209649", "title": "The significance of the imprint cytology in breast biopsy diagnosis.", "content": "Tissue biopsies of the breast with and without carcinomas were examined simultaneously by intraoperative histology and imprint cytology. In 95 per cent of the cases there was a good agreement between the histologic and cytologic diagnoses. The reliability of the imprint cytology was tested in some complicated cases such as proliferating fibroadenomas, pseudoinvasive adenosis and carcinomas. In 20.2 per cent of the cases with carcinoma, the tumor cells showed peculiar intracytoplasmic inclusions, whereas such inclusions were found only in 0.43 per cent of the biopsies of mammas without carcinoma. Their morphological variations and the histochemical pattern are discussed. The results have demonstrated that simultaneous cytologic examination of unfixed mamma biopsies can be a good screening method and that the intracytoplasmic inclusions may be an especially helpful histopathologic feature in the diagnosis of breast cancer.", "contents": "The significance of the imprint cytology in breast biopsy diagnosis. Tissue biopsies of the breast with and without carcinomas were examined simultaneously by intraoperative histology and imprint cytology. In 95 per cent of the cases there was a good agreement between the histologic and cytologic diagnoses. The reliability of the imprint cytology was tested in some complicated cases such as proliferating fibroadenomas, pseudoinvasive adenosis and carcinomas. In 20.2 per cent of the cases with carcinoma, the tumor cells showed peculiar intracytoplasmic inclusions, whereas such inclusions were found only in 0.43 per cent of the biopsies of mammas without carcinoma. Their morphological variations and the histochemical pattern are discussed. The results have demonstrated that simultaneous cytologic examination of unfixed mamma biopsies can be a good screening method and that the intracytoplasmic inclusions may be an especially helpful histopathologic feature in the diagnosis of breast cancer."}
{"id": "PMID:209654", "title": "[Histotopography of glycosidases in the accessory glands of the boar before and after castration].", "content": "The histochemical distribution of six glycosidases (N-acetyl-beta-glucosaminidase, beta-galactosidase, beta-glucuronidase, alpha-galactosidase, alpha-mannosidase and alpha-fucosidase) was investigated in the prostate, glandula vesicularis and glandula bulbourethralis of castrated and non-castrated adult boars. The functions of the glycosidases in the male accessory sex glands of the boar and their androgen dependence are discussed briefly.", "contents": "[Histotopography of glycosidases in the accessory glands of the boar before and after castration]. The histochemical distribution of six glycosidases (N-acetyl-beta-glucosaminidase, beta-galactosidase, beta-glucuronidase, alpha-galactosidase, alpha-mannosidase and alpha-fucosidase) was investigated in the prostate, glandula vesicularis and glandula bulbourethralis of castrated and non-castrated adult boars. The functions of the glycosidases in the male accessory sex glands of the boar and their androgen dependence are discussed briefly."}
{"id": "PMID:209655", "title": "Plasma lipids and lipoproteins in young patients with brain infarction.", "content": "Thirty-two patients aged 60 or less with brain infarction were examined with regard to possible changes in lipoprotein pattern as compared with a reference group. Except for a lower concentration of total lipids, cholesterol and high-density lipoproteins in the female patients, no difference was demonstrated in the two groups. In all patients a significant reduction in total lipids, cholesterol, triglyceride and all lipoproteins was demonstrated after the acute cerebrovascular accident presumedly due to the stress situation.", "contents": "Plasma lipids and lipoproteins in young patients with brain infarction. Thirty-two patients aged 60 or less with brain infarction were examined with regard to possible changes in lipoprotein pattern as compared with a reference group. Except for a lower concentration of total lipids, cholesterol and high-density lipoproteins in the female patients, no difference was demonstrated in the two groups. In all patients a significant reduction in total lipids, cholesterol, triglyceride and all lipoproteins was demonstrated after the acute cerebrovascular accident presumedly due to the stress situation."}
{"id": "PMID:209656", "title": "Morphological changes in CNS of rats treated with perhexiline maleate (pexid).", "content": "The basic cellular lesion in CNS of suckling rats treated with Pexid was studied by light and electron miroscopy. The most pronounced abnormality, the formation of various intracytoplasmic inclusions, was found in neurons, astrocytes, oligodendrocytes, ependymal cells, endothelial cells and fibroblasts. These abnormal inclusions were generally membrane-bound, although clearly non-membrane-bound inclusions were occasionally found. The several internal patterns of the inclusions were (1) lamellar, both concentric and parallel, (2) reticular and (3) crystalloid. These alterations were completely reversed following withdrawal of the drug. The structural characteristics of the abnormal inclusions in Pexid-treated animals were similar to those found with certain hypocholesterolemic, neuroleptic, anorectic, and antimalarial drugs. This suggests that the inclusions occurring within the cells of animals treated with any of these drugs may develop in a similar manner, and that the formation of such inclusions is likely to be a form of cellular reaction common to certain metabolic disturbances.", "contents": "Morphological changes in CNS of rats treated with perhexiline maleate (pexid). The basic cellular lesion in CNS of suckling rats treated with Pexid was studied by light and electron miroscopy. The most pronounced abnormality, the formation of various intracytoplasmic inclusions, was found in neurons, astrocytes, oligodendrocytes, ependymal cells, endothelial cells and fibroblasts. These abnormal inclusions were generally membrane-bound, although clearly non-membrane-bound inclusions were occasionally found. The several internal patterns of the inclusions were (1) lamellar, both concentric and parallel, (2) reticular and (3) crystalloid. These alterations were completely reversed following withdrawal of the drug. The structural characteristics of the abnormal inclusions in Pexid-treated animals were similar to those found with certain hypocholesterolemic, neuroleptic, anorectic, and antimalarial drugs. This suggests that the inclusions occurring within the cells of animals treated with any of these drugs may develop in a similar manner, and that the formation of such inclusions is likely to be a form of cellular reaction common to certain metabolic disturbances."}
{"id": "PMID:209657", "title": "Light and electron microscopic observations on the relationship between Hirano bodies, neuron and glial perikarya in the human hippocampus.", "content": "Hippocampi from two intellectually normal and four demented subjects were examined in autopsy material. Large Hirano bodies seen by light and electron microscopy were thought to be glial in origin and not to be produced by the perikarya of neurons as has been suggested in the literature. Myelination of two Hirano bodies found in the stratum lacunosum-granulosum where neuron perikarya are rare suggests that these bodies are produced by oligodendroglia. Hirano bodies were found to be associated with neurons showing granulovaculoar degeneration. With electron microscope they were frequently seen to be divided by clefts filled with amorphous material which possibly consisted of free ribosomes.", "contents": "Light and electron microscopic observations on the relationship between Hirano bodies, neuron and glial perikarya in the human hippocampus. Hippocampi from two intellectually normal and four demented subjects were examined in autopsy material. Large Hirano bodies seen by light and electron microscopy were thought to be glial in origin and not to be produced by the perikarya of neurons as has been suggested in the literature. Myelination of two Hirano bodies found in the stratum lacunosum-granulosum where neuron perikarya are rare suggests that these bodies are produced by oligodendroglia. Hirano bodies were found to be associated with neurons showing granulovaculoar degeneration. With electron microscope they were frequently seen to be divided by clefts filled with amorphous material which possibly consisted of free ribosomes."}
{"id": "PMID:209658", "title": "The role of glial fibrillary acidic protein in the diagnosis of central nervous system tumors.", "content": "Eighty glial and non-glial brain tumors have been studied to date using an immunologically specific and highly sensitive method of staining GFA protein which is applicable to formalin fixed and paraffin embedded tissue. Eight of these cases have been described and illustrated in some detail. GFA protein was present in all astrocytes and astrocytomas studied and in a proportion of ependymal cells and ependymomas. Some tumor cells have been demonstrated by this method to be glial despite the complete lack of blue fibrillar staining with PTAH and the absence of all morphological similarity to glial cells. In such cases the demonstration of GFA protein by this method has been valuable in establishing a diagnosis. In addition to its diagnostic value in specific cases, the method promises to shed light on unsolved problems of tumor cytogenesis.", "contents": "The role of glial fibrillary acidic protein in the diagnosis of central nervous system tumors. Eighty glial and non-glial brain tumors have been studied to date using an immunologically specific and highly sensitive method of staining GFA protein which is applicable to formalin fixed and paraffin embedded tissue. Eight of these cases have been described and illustrated in some detail. GFA protein was present in all astrocytes and astrocytomas studied and in a proportion of ependymal cells and ependymomas. Some tumor cells have been demonstrated by this method to be glial despite the complete lack of blue fibrillar staining with PTAH and the absence of all morphological similarity to glial cells. In such cases the demonstration of GFA protein by this method has been valuable in establishing a diagnosis. In addition to its diagnostic value in specific cases, the method promises to shed light on unsolved problems of tumor cytogenesis."}
{"id": "PMID:209659", "title": "Adrenoleukodystrophy. Preliminary report of a connatal case. Light- and electron microscopical, immunohistochemical and biochemical findings.", "content": "This is the first description of a connatal case of adrenoleukodystrophy. The clinical picture consisted of severe psychomotor retardation, convulsions and hypsarrhythmia, but no obvious signs of adrenal insufficiency. Pathologically, the adrenals were small. The entire cortex was largely replaced by large round cells. Ultrastructurally, some cells in the adrenal cortex contained inclusions with electron-lucent clefts surrounded by a membrane. The anterior pituitary lobe could be demonstrated to have produced ACTH. The central nervous system showed extensive zones of demyelination in the brainstem, the cerebellum and the right-sided capsula interna. In the demyelinated areas there was sudanophilic breakdown and an intense gliosis. Ongoing demyelination could also be demonstrated by the chemical analysis. In the gray matter there waere micropolygyria of the insular cortex and swollen nerve cells in the nucleus arcuatus. Ultrastructure revealed the type of inclusions in the microglia of the same type as in the adrenals, and a different type of inclusions in unidentifiable cells, possibly neurons. These latter inclusions consisted of loosely stacked lamellar material. The findings are interpreted as further evidence of storage taking place in this disease.", "contents": "Adrenoleukodystrophy. Preliminary report of a connatal case. Light- and electron microscopical, immunohistochemical and biochemical findings. This is the first description of a connatal case of adrenoleukodystrophy. The clinical picture consisted of severe psychomotor retardation, convulsions and hypsarrhythmia, but no obvious signs of adrenal insufficiency. Pathologically, the adrenals were small. The entire cortex was largely replaced by large round cells. Ultrastructurally, some cells in the adrenal cortex contained inclusions with electron-lucent clefts surrounded by a membrane. The anterior pituitary lobe could be demonstrated to have produced ACTH. The central nervous system showed extensive zones of demyelination in the brainstem, the cerebellum and the right-sided capsula interna. In the demyelinated areas there was sudanophilic breakdown and an intense gliosis. Ongoing demyelination could also be demonstrated by the chemical analysis. In the gray matter there waere micropolygyria of the insular cortex and swollen nerve cells in the nucleus arcuatus. Ultrastructure revealed the type of inclusions in the microglia of the same type as in the adrenals, and a different type of inclusions in unidentifiable cells, possibly neurons. These latter inclusions consisted of loosely stacked lamellar material. The findings are interpreted as further evidence of storage taking place in this disease."}
{"id": "PMID:209664", "title": "Serum prolactin, FSH and LH during puberty in girls and boys.", "content": "Serum prolactin, follicle-stimulating hormone and luteinizing hormone were determined in 200 girls and 80 boys. The boys have been examined on three occasions at one-year intervals and the girls twice at 1.5-year intervals. In girls, serum FSH rapidly increased in the youngest age groups (7.5-11.5 years), whereas in boys, the increase took place later and the first significant increase was seen between age groups 9.5 and 12.5 years. In girls, a rise in serum LH took place later than that of FSH (between 10.5 and 11.5 years), and LH peaked at 13.0-13.5 years. In boys, the timing in the changes of serum LH closely resembled that of FSH. The girls displayed a significant increase in serum prolactin between 7.5 and 8.5 years, and this was followed by a slow progressive increase. In the group of boys, serum prolactin did not show any significant changes. In girls, there was a correlation between serum LH and body weight, as well as calculated fat amount and body fat percentage early in puberty. There was no correlation between serum LH and chronological or bone age in this age group, which suggests that the correlation found is not due to age-related parallel phenomena.", "contents": "Serum prolactin, FSH and LH during puberty in girls and boys. Serum prolactin, follicle-stimulating hormone and luteinizing hormone were determined in 200 girls and 80 boys. The boys have been examined on three occasions at one-year intervals and the girls twice at 1.5-year intervals. In girls, serum FSH rapidly increased in the youngest age groups (7.5-11.5 years), whereas in boys, the increase took place later and the first significant increase was seen between age groups 9.5 and 12.5 years. In girls, a rise in serum LH took place later than that of FSH (between 10.5 and 11.5 years), and LH peaked at 13.0-13.5 years. In boys, the timing in the changes of serum LH closely resembled that of FSH. The girls displayed a significant increase in serum prolactin between 7.5 and 8.5 years, and this was followed by a slow progressive increase. In the group of boys, serum prolactin did not show any significant changes. In girls, there was a correlation between serum LH and body weight, as well as calculated fat amount and body fat percentage early in puberty. There was no correlation between serum LH and chronological or bone age in this age group, which suggests that the correlation found is not due to age-related parallel phenomena."}
{"id": "PMID:209665", "title": "Mechanism of the formation of megamitochondria by copper-chelating agents. V. Further studies on isolated megamitochondria.", "content": "Effect of cuprizone has been studied on some biochemical properties of megamitochondria obtained from the mouse liver. (1) Contents of Ca2+, Mg2+ and Cu2+ in the blood or the liver homogenates were not altered by cuprizone intoxication, whereas those in liver mitochondria were significantly altered: after 3-4 days' intoxication, content of Ca2+ was decreased and was remarkably increased after 14-15 days' intoxication. Content of Mg2+ behaved contrarily. (2) Both cytochrome oxidase and ATPase activities were unchanged in the liver megamitochondria, but monoamine oxidase (MAO) activity was significantly decreased. Value of I50 (50% inhibition) for MAO was determined to be 0.33 mM using the control liver mitochondria. Cuprizone had almost no effect on MAO activity of kidney or heart mitochondria both in vivo and in vitro. (3) The amount of lysolecithin was increased in the liver megamitochondria. These results were discussed in the light of membrane fusion phenomenon which plays a key role in the mechanism of megamitochondrial formation.", "contents": "Mechanism of the formation of megamitochondria by copper-chelating agents. V. Further studies on isolated megamitochondria. Effect of cuprizone has been studied on some biochemical properties of megamitochondria obtained from the mouse liver. (1) Contents of Ca2+, Mg2+ and Cu2+ in the blood or the liver homogenates were not altered by cuprizone intoxication, whereas those in liver mitochondria were significantly altered: after 3-4 days' intoxication, content of Ca2+ was decreased and was remarkably increased after 14-15 days' intoxication. Content of Mg2+ behaved contrarily. (2) Both cytochrome oxidase and ATPase activities were unchanged in the liver megamitochondria, but monoamine oxidase (MAO) activity was significantly decreased. Value of I50 (50% inhibition) for MAO was determined to be 0.33 mM using the control liver mitochondria. Cuprizone had almost no effect on MAO activity of kidney or heart mitochondria both in vivo and in vitro. (3) The amount of lysolecithin was increased in the liver megamitochondria. These results were discussed in the light of membrane fusion phenomenon which plays a key role in the mechanism of megamitochondrial formation."}
{"id": "PMID:209666", "title": "Effects of isoprenaline on the time course of the cyclic AMP level in rat uterus.", "content": "Isoprenaline markedly relaxed rat uterine muscle and increased its content of cyclic AMP. The cyclic AMP concentration reached its highest value, about ten times the control after 3 min., after which it declined rather quickly at first but later more slowly. After 60 min. the cyclic AMP content reached twice the prestimulation value. The muscle remained relaxed all the time. If the incubation medium from the uterus treated with isoprenaline for 60 min. was added to a fresh muscle, a normal response was elicited. Addition of a new dose of isoprenaline to a muscle previously incubated with isoprenaline for 60 min. only gave a minimal rise in cyclic AMP after 3 min. The presence of catechol or corticosterone, which both decreased the inactivation of isoprenaline, showed no effect on the decrease of the isoprenaline-stimulated cyclic AMP level. Nor could the decrease in the cyclic AMP response be prevented in the presence of GTP,F-, adenosine or in Ca2+-deficient medium. The addition of theophylline and puromycin both lead to a slower decline of cyclic AMP content, but after 60 min. the value returned to near that seen ater only isoprenaline. Our studies on isoprenaline-induced desensitization of rat uterus have led us to the conclusion that the change in the capacity of the preparations to accumulate cyclic AMP may be a result of either changes in the beta-adrenoceptors or in the cyclase-system.", "contents": "Effects of isoprenaline on the time course of the cyclic AMP level in rat uterus. Isoprenaline markedly relaxed rat uterine muscle and increased its content of cyclic AMP. The cyclic AMP concentration reached its highest value, about ten times the control after 3 min., after which it declined rather quickly at first but later more slowly. After 60 min. the cyclic AMP content reached twice the prestimulation value. The muscle remained relaxed all the time. If the incubation medium from the uterus treated with isoprenaline for 60 min. was added to a fresh muscle, a normal response was elicited. Addition of a new dose of isoprenaline to a muscle previously incubated with isoprenaline for 60 min. only gave a minimal rise in cyclic AMP after 3 min. The presence of catechol or corticosterone, which both decreased the inactivation of isoprenaline, showed no effect on the decrease of the isoprenaline-stimulated cyclic AMP level. Nor could the decrease in the cyclic AMP response be prevented in the presence of GTP,F-, adenosine or in Ca2+-deficient medium. The addition of theophylline and puromycin both lead to a slower decline of cyclic AMP content, but after 60 min. the value returned to near that seen ater only isoprenaline. Our studies on isoprenaline-induced desensitization of rat uterus have led us to the conclusion that the change in the capacity of the preparations to accumulate cyclic AMP may be a result of either changes in the beta-adrenoceptors or in the cyclase-system."}
{"id": "PMID:209668", "title": "Plasma cyclic AMP in manic-depressive illness.", "content": "The postulated disturbance of cyclic AMP (cAMP) in manic-depressive illness was investigated by using plasma as the biological material. Cyclic AMP was measured by a protein-binding assay, which was found very satisfactory for the purpose of this study. In the drug-free state, depressed patients (n = 28) had significantly lower and manic patients (n = 9) significantly higher plasma concentrations of cAMP than controls. Unmedicated manic-depressive subjects had normal cAMP levels during normothymic phases (n = 7). Cyclic AMP was reduced by neuroleptics in mania and elevated by tricyclics in depression. Lithium exerted a normalizing effect on cAMP in both phases of the illness. It is concluded that manic-depressive illness is associated with a disturbance in the cAMP system. The use of plasma rather than urine for the investigation of the state of cAMP in psychiatric disorders is advocated.", "contents": "Plasma cyclic AMP in manic-depressive illness. The postulated disturbance of cyclic AMP (cAMP) in manic-depressive illness was investigated by using plasma as the biological material. Cyclic AMP was measured by a protein-binding assay, which was found very satisfactory for the purpose of this study. In the drug-free state, depressed patients (n = 28) had significantly lower and manic patients (n = 9) significantly higher plasma concentrations of cAMP than controls. Unmedicated manic-depressive subjects had normal cAMP levels during normothymic phases (n = 7). Cyclic AMP was reduced by neuroleptics in mania and elevated by tricyclics in depression. Lithium exerted a normalizing effect on cAMP in both phases of the illness. It is concluded that manic-depressive illness is associated with a disturbance in the cAMP system. The use of plasma rather than urine for the investigation of the state of cAMP in psychiatric disorders is advocated."}
{"id": "PMID:209669", "title": "Survey of serum lipid levels in Icelandic men aged 34-61 years. An epidemiological and statistical evaluation.", "content": "This report presents the results of serum beta-lipoprotein, total cholesterol and triglycerides determinations in a male population surveyed 1967--'68. This was the first stage (stage I) in a prospective health survey conducted by the Icelandic Health Association. The area of study was the city of Reykjav\u00edk with adjacent suburbs and communes. The population invited was 1/3 of each of 16 year-groups of males in the age-interval 34-61 years. The population was selected from the National Roster according to birthdays i.e. the 1st, 4th, 7th,.. of each month, the total number being 2.955. The response was 75.1%. B-lipoproteins were determined with the Hyland Beta-L Test, total cholesterol and triglycerides on Technicon AutoAnalyzer (i) according to Technicon Methodology N-24a, and a modification of the method of Kessler and Lederer respectively. Control sera were run in connection with cholesterol- and triglycerides determinations. Serum cholesterol levels were similar to the highest reported from other countries contrary to the triglycerides levels which are in the low range. The mean values and lower centiles are practically independent of age whereas the higher centiles are markedly age-dependent. A seasonal variation for the cholesterol weekly mean values was found. These values were highest in winter and lowest in summer, the difference estimated to be 30-40 mg%. No seasonal variation of triglycerides was found. Centile-flowdiagrams for these blood lipids are presented and the use of similar flowdiagrams is suggested as an aid to bridge a gap between the interpretation of cross-sectional and longitudinal studies.", "contents": "Survey of serum lipid levels in Icelandic men aged 34-61 years. An epidemiological and statistical evaluation. This report presents the results of serum beta-lipoprotein, total cholesterol and triglycerides determinations in a male population surveyed 1967--'68. This was the first stage (stage I) in a prospective health survey conducted by the Icelandic Health Association. The area of study was the city of Reykjav\u00edk with adjacent suburbs and communes. The population invited was 1/3 of each of 16 year-groups of males in the age-interval 34-61 years. The population was selected from the National Roster according to birthdays i.e. the 1st, 4th, 7th,.. of each month, the total number being 2.955. The response was 75.1%. B-lipoproteins were determined with the Hyland Beta-L Test, total cholesterol and triglycerides on Technicon AutoAnalyzer (i) according to Technicon Methodology N-24a, and a modification of the method of Kessler and Lederer respectively. Control sera were run in connection with cholesterol- and triglycerides determinations. Serum cholesterol levels were similar to the highest reported from other countries contrary to the triglycerides levels which are in the low range. The mean values and lower centiles are practically independent of age whereas the higher centiles are markedly age-dependent. A seasonal variation for the cholesterol weekly mean values was found. These values were highest in winter and lowest in summer, the difference estimated to be 30-40 mg%. No seasonal variation of triglycerides was found. Centile-flowdiagrams for these blood lipids are presented and the use of similar flowdiagrams is suggested as an aid to bridge a gap between the interpretation of cross-sectional and longitudinal studies."}
{"id": "PMID:209670", "title": "Early diagnosis of cancer by gastricbiopsy.", "content": "On the basis of 350 gastric biopsies the difficulties of early diagnosis of cancer are discussed. The technical and morphological stumbling blocks of evaluation are reviewed. The differences between the gross and microscopic diagnoses, the more important causes of histologic error are dealt with.", "contents": "Early diagnosis of cancer by gastricbiopsy. On the basis of 350 gastric biopsies the difficulties of early diagnosis of cancer are discussed. The technical and morphological stumbling blocks of evaluation are reviewed. The differences between the gross and microscopic diagnoses, the more important causes of histologic error are dealt with."}
{"id": "PMID:209671", "title": "Photochemical reactions of cytochrome oxidase at low temperatures.", "content": "The unique of CO-cytochrome oxidase as first noted by Yonetani et al. (22) is that after its photodissociation at low temperatures recombination occurs as the sample temperature is raised, but at temperatures considerably higher than those for other CO-heme and CO-hemoprotein complexes; that is, the half recombination temperature is 180 K contrary to 25-30 K for other CO complexes. The photodissociability, however, disappeared when monomeric cytochrome oxidase was treated with pCMB to remove an intrinsic copper, the significance of which in CO complex formation was thus demonstrated. It is proposed that the copper is situated close to heme a and traps the photodissociated CO. The access of the trapped CO to the heme a to resume the original binding is effected only when sufficient energy for thermal agitation is provided by elevating the sample temperature. During the course of this study, new photo- and thermochromic properties were observed with the reduced enzyme by cooling it in liquid nitrogen after preincubation at pH 8.6 to 10.5. The characteristic bands appeared at 575 and 428 nm and diminished when this ample was illuminated at 26 K. As the sample temperature was raised these bands were restored with a half transition temperature of 80 K. When the reduced oxidase had been complexed with CO, cyanide or azide, or treated with pCMB, such a unique species did not appear. The enthalpy change of 1.16 kcal/mol for the formation of this species as well as the above-described properties suggests that the hydrogen bond between the formyl side group of heme a and one of seven sulfhydryl groups in cytochrome oxidase is responsible for the appearance and disappearance of this new species. Based on these results a schematic model has been proposed for the photo- and thermochromism of cytochrome oxidase at cryogenic temperatures and for the microenvironment of the prosthetic heme a and copper in this enzyme. On the other hand, contrary to the central dogma of Warburg that all CO-heme and CO-hemoprotein complexes are photodissociable, we observed little photodissociability with some CO-heme complexes, especially at very low temperatures, and presented a view that depending on the bond type between CO and heme iron the efficiency of photodissociation is so varied that under certain conditions practically no photodissociation occurs. According to this view a tilted arrangement of the ligated CO towards the heme plane accompanying a large extent of overlapping of the dpi(Fe) and the pi* antibonding orbital on the CO facilitates photodissociation. In addition to our own observations of photochemical properties of cytochrome oxidase and heme model compounds, recent photodynamic studies carried out by other investigator on CO-heme and CO-hemoproteins are summarized and the validity and limitation of their models are discussed.", "contents": "Photochemical reactions of cytochrome oxidase at low temperatures. The unique of CO-cytochrome oxidase as first noted by Yonetani et al. (22) is that after its photodissociation at low temperatures recombination occurs as the sample temperature is raised, but at temperatures considerably higher than those for other CO-heme and CO-hemoprotein complexes; that is, the half recombination temperature is 180 K contrary to 25-30 K for other CO complexes. The photodissociability, however, disappeared when monomeric cytochrome oxidase was treated with pCMB to remove an intrinsic copper, the significance of which in CO complex formation was thus demonstrated. It is proposed that the copper is situated close to heme a and traps the photodissociated CO. The access of the trapped CO to the heme a to resume the original binding is effected only when sufficient energy for thermal agitation is provided by elevating the sample temperature. During the course of this study, new photo- and thermochromic properties were observed with the reduced enzyme by cooling it in liquid nitrogen after preincubation at pH 8.6 to 10.5. The characteristic bands appeared at 575 and 428 nm and diminished when this ample was illuminated at 26 K. As the sample temperature was raised these bands were restored with a half transition temperature of 80 K. When the reduced oxidase had been complexed with CO, cyanide or azide, or treated with pCMB, such a unique species did not appear. The enthalpy change of 1.16 kcal/mol for the formation of this species as well as the above-described properties suggests that the hydrogen bond between the formyl side group of heme a and one of seven sulfhydryl groups in cytochrome oxidase is responsible for the appearance and disappearance of this new species. Based on these results a schematic model has been proposed for the photo- and thermochromism of cytochrome oxidase at cryogenic temperatures and for the microenvironment of the prosthetic heme a and copper in this enzyme. On the other hand, contrary to the central dogma of Warburg that all CO-heme and CO-hemoprotein complexes are photodissociable, we observed little photodissociability with some CO-heme complexes, especially at very low temperatures, and presented a view that depending on the bond type between CO and heme iron the efficiency of photodissociation is so varied that under certain conditions practically no photodissociation occurs. According to this view a tilted arrangement of the ligated CO towards the heme plane accompanying a large extent of overlapping of the dpi(Fe) and the pi* antibonding orbital on the CO facilitates photodissociation. In addition to our own observations of photochemical properties of cytochrome oxidase and heme model compounds, recent photodynamic studies carried out by other investigator on CO-heme and CO-hemoproteins are summarized and the validity and limitation of their models are discussed."}
{"id": "PMID:209667", "title": "[Psychological links and coronary diseases. II. Psychological correlations of certain physiological variables (author's transl)].", "content": "In this study, correlations were tabulated between physiological and psychological measurements drawn from a group of 21 infarct patients and a matching group of 21 normal subjects. The physiological variables taken under consideration are the number of platelets, the beta-lipoproteines and the systolic blood pressure; all these variables were tested under stress and at rest. On the top, fibrinogene at rest, cortisol under stress and heart rate under conditions of \"intake\" and \"rejection\" were also measured. The psychological assessment was achieved by the MMPI. Several psychological traits link with physiological parameters to be considered as cardiovascular risks. However, these links are mostly specific; moreover, they vary under different experimental conditions. In other words, different neuro-behavioral patterns seem to operate at rest and under stress. The links between psychological and physiological variables vary also between normal subjects and infarct patients. Normal subjects as well as infarct patients show a relationship between neurotic traits and genuine physiological reactions. However, among the formers, these neurotic traits are in closer relationship with inhibitions as among heart patients. Psychological risk factors in cardiovascular disorders appear to be related with a genuine expression of conflictual affects leading to inadequate physiological responses; when these reactions are repeated in time, functional disorders may induce organic lesions.", "contents": "[Psychological links and coronary diseases. II. Psychological correlations of certain physiological variables (author's transl)]. In this study, correlations were tabulated between physiological and psychological measurements drawn from a group of 21 infarct patients and a matching group of 21 normal subjects. The physiological variables taken under consideration are the number of platelets, the beta-lipoproteines and the systolic blood pressure; all these variables were tested under stress and at rest. On the top, fibrinogene at rest, cortisol under stress and heart rate under conditions of \"intake\" and \"rejection\" were also measured. The psychological assessment was achieved by the MMPI. Several psychological traits link with physiological parameters to be considered as cardiovascular risks. However, these links are mostly specific; moreover, they vary under different experimental conditions. In other words, different neuro-behavioral patterns seem to operate at rest and under stress. The links between psychological and physiological variables vary also between normal subjects and infarct patients. Normal subjects as well as infarct patients show a relationship between neurotic traits and genuine physiological reactions. However, among the formers, these neurotic traits are in closer relationship with inhibitions as among heart patients. Psychological risk factors in cardiovascular disorders appear to be related with a genuine expression of conflictual affects leading to inadequate physiological responses; when these reactions are repeated in time, functional disorders may induce organic lesions."}
{"id": "PMID:209676", "title": "Lipoprotein lipase and postheparin esterase activity in primary hyperlipoproteinaemia type IV and V.", "content": "In a study of the aetiopathogenesis of primary hyperlipoproteinaemias, which has not yet been elucidated, we paid attention to the heparin-activated lipolytic enzymes. Lipoprotein lipase (LPL) and postheparin esterase (PHE) activity was determined in 35 patients with primary hyperlipoproteinaemia (HLP) type IV (average age 50 years), 28 with type V (average age 48 years) and 2 with type III (57 and 62 years). Since PHE activity is correlated to sex and in women also to age, these factors had to be taken into account. The average activity values for the given enzymes in the patients group did not differ from the results in the control group. From these enzymes activities we tried to analyse the findings in individual cases in which the values were lower or higher than the control group range. The low PHE activity in some patients with type IV and V was evidently secondary and due to hepatobiliary disorder (most frequently liver steatosis). The simultaneous elevation of LPL and PHE activity in type IV and V patients with a high serum lipoprotein concentration shows that the response of patients with extreme HLP to heparin is more pronounced. The low PHE activity in type III (tested in only 2 patients) could possibly indicate the liver disorder on which this metabolic disease may be based.", "contents": "Lipoprotein lipase and postheparin esterase activity in primary hyperlipoproteinaemia type IV and V. In a study of the aetiopathogenesis of primary hyperlipoproteinaemias, which has not yet been elucidated, we paid attention to the heparin-activated lipolytic enzymes. Lipoprotein lipase (LPL) and postheparin esterase (PHE) activity was determined in 35 patients with primary hyperlipoproteinaemia (HLP) type IV (average age 50 years), 28 with type V (average age 48 years) and 2 with type III (57 and 62 years). Since PHE activity is correlated to sex and in women also to age, these factors had to be taken into account. The average activity values for the given enzymes in the patients group did not differ from the results in the control group. From these enzymes activities we tried to analyse the findings in individual cases in which the values were lower or higher than the control group range. The low PHE activity in some patients with type IV and V was evidently secondary and due to hepatobiliary disorder (most frequently liver steatosis). The simultaneous elevation of LPL and PHE activity in type IV and V patients with a high serum lipoprotein concentration shows that the response of patients with extreme HLP to heparin is more pronounced. The low PHE activity in type III (tested in only 2 patients) could possibly indicate the liver disorder on which this metabolic disease may be based."}
{"id": "PMID:209677", "title": "Determination of alpha-amylase activity in duodenal contents with the blue starch polymer.", "content": "The use of the blue starch polymer (Phadebas tablets) for the determination of duodenal alpha-amylase is described. 0.05% bovine or human albumin solutions are necessary for dissolution of substrate tablets as well as for dilution of duodenal contents. Concentration and output values of duodenal amylase before and after cholecystokinin-pancreozymin and secretin stimulation display a close correlation of the chromogenic and saccharogenic method. The average error of duodenal alpha-amylase in parallel examinations is low with both methods and their relative accuracy is practically the same. The chromogenic method is considered more simple and rapid.", "contents": "Determination of alpha-amylase activity in duodenal contents with the blue starch polymer. The use of the blue starch polymer (Phadebas tablets) for the determination of duodenal alpha-amylase is described. 0.05% bovine or human albumin solutions are necessary for dissolution of substrate tablets as well as for dilution of duodenal contents. Concentration and output values of duodenal amylase before and after cholecystokinin-pancreozymin and secretin stimulation display a close correlation of the chromogenic and saccharogenic method. The average error of duodenal alpha-amylase in parallel examinations is low with both methods and their relative accuracy is practically the same. The chromogenic method is considered more simple and rapid."}
{"id": "PMID:209679", "title": "Lisfranc's fracture-dislocation: a manifestation of peripheral neuropathy.", "content": "Lisfranc's fracture-dislocation may be secondary to acute trauma, but on the basis of our experience with seven cases, it is more commonly a manifestation of repetitive subclinical trauma in patients with a neuropathic disorder. Separation of these two groups of patients is important, since those with acute trauma require reduction and those with a neuropathy need only be treated with non-weight bearing. All patients with Lisfranc's fracture-dislocation and without a specific history of acute trauma should be evaluated for the possibility of diabetes mellitus or another cause of sensory neuropathy.", "contents": "Lisfranc's fracture-dislocation: a manifestation of peripheral neuropathy. Lisfranc's fracture-dislocation may be secondary to acute trauma, but on the basis of our experience with seven cases, it is more commonly a manifestation of repetitive subclinical trauma in patients with a neuropathic disorder. Separation of these two groups of patients is important, since those with acute trauma require reduction and those with a neuropathy need only be treated with non-weight bearing. All patients with Lisfranc's fracture-dislocation and without a specific history of acute trauma should be evaluated for the possibility of diabetes mellitus or another cause of sensory neuropathy."}
{"id": "PMID:209678", "title": "An evaluation of the absorption spectra of antigens from Entamoeba histolytica (Ibadan strains).", "content": "By means of chromatography different fractions of antigens from Entamoeba histolytica (Ibadan Strains) have been separated. All the different fractions have been tested for antigenic reactivity using agar gel diffusion technique. The intact antigen, as well as, the three antigenically reactive fractions were found to have ultra-violet absorption spectra in the region 258 and 278 millimicron. By virtue of this physico-chemical property amoebic extract(s) was found to simulate a mononucleotide Deoxy-5-methyl-cytidilic-acid. Such a unique structure of the extracts was used to suggest a mechanism for the possible low antigenicity of the organism based on its inability to induce a protective antibody response in human amoebiasis.", "contents": "An evaluation of the absorption spectra of antigens from Entamoeba histolytica (Ibadan strains). By means of chromatography different fractions of antigens from Entamoeba histolytica (Ibadan Strains) have been separated. All the different fractions have been tested for antigenic reactivity using agar gel diffusion technique. The intact antigen, as well as, the three antigenically reactive fractions were found to have ultra-violet absorption spectra in the region 258 and 278 millimicron. By virtue of this physico-chemical property amoebic extract(s) was found to simulate a mononucleotide Deoxy-5-methyl-cytidilic-acid. Such a unique structure of the extracts was used to suggest a mechanism for the possible low antigenicity of the organism based on its inability to induce a protective antibody response in human amoebiasis."}
{"id": "PMID:209680", "title": "Fine needle aspiration biopsy in the diagnosis of mediastinal lesions.", "content": "In the presence of a mediastinal mass, fine needle aspiration biopsy is an alternative to other time-consuming and expensive diagnostic procedures. We have performed a total of 25 fine needle aspiration biopsies of mediastinal lesions in 18 patients. Although our material is too limited to reach definite conclusions as to risks, we have found the technique enables a high percentage of positive diagnoses and is well tolerated by the patient.", "contents": "Fine needle aspiration biopsy in the diagnosis of mediastinal lesions. In the presence of a mediastinal mass, fine needle aspiration biopsy is an alternative to other time-consuming and expensive diagnostic procedures. We have performed a total of 25 fine needle aspiration biopsies of mediastinal lesions in 18 patients. Although our material is too limited to reach definite conclusions as to risks, we have found the technique enables a high percentage of positive diagnoses and is well tolerated by the patient."}
{"id": "PMID:209681", "title": "Wilms' tumor to the heart: clinical and radiographic evaluation.", "content": "The clinical and radiographic appearances of four children with cardiac extension of Wilms' tumor and four cases from the literature are described. Four of the eight children were seen for \"cardiac problems\" and four for \"routine\" Wilms' tumor. In those \"routine\" cases, there were no clinical suggestions of inferior vena cava or cardiac extension. Preoperative screening for tumor extension may be crucial. However, because of the rarity of cardiac extension, it would be appropriate to screen patients by noninvasive methods such as gray scale ultrasound of the abdomen, echocardiography, or computed tomography before any invasive procedure is considered.", "contents": "Wilms' tumor to the heart: clinical and radiographic evaluation. The clinical and radiographic appearances of four children with cardiac extension of Wilms' tumor and four cases from the literature are described. Four of the eight children were seen for \"cardiac problems\" and four for \"routine\" Wilms' tumor. In those \"routine\" cases, there were no clinical suggestions of inferior vena cava or cardiac extension. Preoperative screening for tumor extension may be crucial. However, because of the rarity of cardiac extension, it would be appropriate to screen patients by noninvasive methods such as gray scale ultrasound of the abdomen, echocardiography, or computed tomography before any invasive procedure is considered."}
{"id": "PMID:209685", "title": "The ultrastructure of the neonatal pig colon.", "content": "The neonatal pig colon has several unique structural and developmental features. At birth it has a variable population of epithelial cells which in their arrangement on villus-like protrusions and in their capability for protein uptake into large preformed supranuclear vacuoles closely resemble neonatal ileal cells. Such villus-like protrusions and vacuolated cells are not present in the 2-day-old piglet. On the first day after birth absorptive epithelial cells which lack supranuclear vacuoles transiently accumulate a large number of lipid droplets, each separated from the cytoplasm only by a proteolipid interface. None of the much smaller lipid droplets bounded by a unit membrane of the smooth endoplasmic reticulum and characteristic of normal small intestinal fat uptake were ever seen in these cells. Very few of the large lipid drops remain on the second day after birth. This initial capacity of the colon for protein and lipid uptake never reappears. The pattern of colonic amino acid transport also changes markedly in the first four days of independent life and this may be correlated with the observation that the absorptive cells at birth have microvilli which are twice the length of those on similar cells at and after two days old. These morphological results are discussed in terms of implied functional changes in the neonatal period.", "contents": "The ultrastructure of the neonatal pig colon. The neonatal pig colon has several unique structural and developmental features. At birth it has a variable population of epithelial cells which in their arrangement on villus-like protrusions and in their capability for protein uptake into large preformed supranuclear vacuoles closely resemble neonatal ileal cells. Such villus-like protrusions and vacuolated cells are not present in the 2-day-old piglet. On the first day after birth absorptive epithelial cells which lack supranuclear vacuoles transiently accumulate a large number of lipid droplets, each separated from the cytoplasm only by a proteolipid interface. None of the much smaller lipid droplets bounded by a unit membrane of the smooth endoplasmic reticulum and characteristic of normal small intestinal fat uptake were ever seen in these cells. Very few of the large lipid drops remain on the second day after birth. This initial capacity of the colon for protein and lipid uptake never reappears. The pattern of colonic amino acid transport also changes markedly in the first four days of independent life and this may be correlated with the observation that the absorptive cells at birth have microvilli which are twice the length of those on similar cells at and after two days old. These morphological results are discussed in terms of implied functional changes in the neonatal period."}
{"id": "PMID:209686", "title": "Dispersion of cisternae of rough endoplasmic reticulum in aging CNS neurons: a strictly linear trend.", "content": "Dispersion of cisternae of rough endoplasmic reticulum (RER) in aging rats has been determined quantitatively for mitral cells of the olfactory bulb and Purkinje cells of the cerebellum using a recently published morphometric technique (Cruz Orive, '76). In both cell types dispersion of cisternae occurred throughout the period studied and in a linear fashion. The observed RER dispersion cannot be attributed to a decrease in the total amount of RER, since the total amount of RER was constant in Purkinje cells and increased in mitral cells during the age studied.", "contents": "Dispersion of cisternae of rough endoplasmic reticulum in aging CNS neurons: a strictly linear trend. Dispersion of cisternae of rough endoplasmic reticulum (RER) in aging rats has been determined quantitatively for mitral cells of the olfactory bulb and Purkinje cells of the cerebellum using a recently published morphometric technique (Cruz Orive, '76). In both cell types dispersion of cisternae occurred throughout the period studied and in a linear fashion. The observed RER dispersion cannot be attributed to a decrease in the total amount of RER, since the total amount of RER was constant in Purkinje cells and increased in mitral cells during the age studied."}
{"id": "PMID:209687", "title": "Dissection of a continuous distribution: red cell galactokinase activity in blacks.", "content": "A significant difference between blacks and whites in the distribution of red cell galactokinase (GALK) has been found by Tedesco et al. [2]. From the shapes of the distributions, it was inferred that whites are essentially all homozygous for one allele (GALKA), but blacks are polymorphic. A second allele (GALKP), for lower GALK activity, is presented at high frequency in blacks but rare or absent in whites. This paper presents a method which, assuming the genetic model presented, estimates the genotype composition of the black sample. We make some reasonable biochemical assumptions and fit a mixture of three normal distributions to the black data to obtain an estimate of p, the frequency of GALKA in blacks. The fit of the model to the data is excellent and the best estimate of p is .217 +/- .025. Since admixture of white genes in blacks from the United States is known to be about 20%, the value of p implies that virtually all GALKA alleles were introduced by admixture, and that the ancestral black population was monomorphic for GALKP. If whites are indeed monomorphic for GALKA, they differ from unmixed blacks by a full gene substitution at the locus for GALK.", "contents": "Dissection of a continuous distribution: red cell galactokinase activity in blacks. A significant difference between blacks and whites in the distribution of red cell galactokinase (GALK) has been found by Tedesco et al. [2]. From the shapes of the distributions, it was inferred that whites are essentially all homozygous for one allele (GALKA), but blacks are polymorphic. A second allele (GALKP), for lower GALK activity, is presented at high frequency in blacks but rare or absent in whites. This paper presents a method which, assuming the genetic model presented, estimates the genotype composition of the black sample. We make some reasonable biochemical assumptions and fit a mixture of three normal distributions to the black data to obtain an estimate of p, the frequency of GALKA in blacks. The fit of the model to the data is excellent and the best estimate of p is .217 +/- .025. Since admixture of white genes in blacks from the United States is known to be about 20%, the value of p implies that virtually all GALKA alleles were introduced by admixture, and that the ancestral black population was monomorphic for GALKP. If whites are indeed monomorphic for GALKA, they differ from unmixed blacks by a full gene substitution at the locus for GALK."}
{"id": "PMID:209691", "title": "Aniridia, cataracts, and Wilms' tumor in monozygous twins.", "content": "We studied the first instance of aniridia-Wilms' tumor syndrome in twins who were mentally retarded. Both of them had congenital aniridia, cataracts, and glaucoma; only one subsequently developed a Wilms' tumor. A two-allele, two-step mutation is the most likely explanation of this genetically abnormal syndrome in twins. The aniridia-Wilms' tumor syndrome in twins further documents the relationship of teratogenic malformations and neoplasias.", "contents": "Aniridia, cataracts, and Wilms' tumor in monozygous twins. We studied the first instance of aniridia-Wilms' tumor syndrome in twins who were mentally retarded. Both of them had congenital aniridia, cataracts, and glaucoma; only one subsequently developed a Wilms' tumor. A two-allele, two-step mutation is the most likely explanation of this genetically abnormal syndrome in twins. The aniridia-Wilms' tumor syndrome in twins further documents the relationship of teratogenic malformations and neoplasias."}
{"id": "PMID:209692", "title": "Collagenase in experimental carbon tetrachloride cirrhosis of the liver.", "content": "The presence and distribution of collagenase in experimental CCl4 cirrhosis of the liver in rats has been studied by immunohistochemical techniques. A monospecific anti-rat uterus collagenase antibody was raised in rabbits and used for indirect immunofluorescence staining of liver sections obtained from rats in both the reversible and irreversible stages of CCl4-induced cirrhosis. Collagenase is present assoicated with connective tissue septums as long as cirrhosis is reversible, and it is not detectable in the irreversible stage. In animals sacrificed during the transition between the reversible and irreversible stages of cirrhosis, collagenase appeared bound to the outer surfaces of connective tissue septums and was absent from the deeper portions. These observation suggest that the irreversibility of experimental CCl4 cirrhosis of the liver is associated with a disturbance in the mechanisms of collagen degradation, which may be a deficiency in collagenase activity, a change in the susceptibility of the substrate, or a combination of both factors.", "contents": "Collagenase in experimental carbon tetrachloride cirrhosis of the liver. The presence and distribution of collagenase in experimental CCl4 cirrhosis of the liver in rats has been studied by immunohistochemical techniques. A monospecific anti-rat uterus collagenase antibody was raised in rabbits and used for indirect immunofluorescence staining of liver sections obtained from rats in both the reversible and irreversible stages of CCl4-induced cirrhosis. Collagenase is present assoicated with connective tissue septums as long as cirrhosis is reversible, and it is not detectable in the irreversible stage. In animals sacrificed during the transition between the reversible and irreversible stages of cirrhosis, collagenase appeared bound to the outer surfaces of connective tissue septums and was absent from the deeper portions. These observation suggest that the irreversibility of experimental CCl4 cirrhosis of the liver is associated with a disturbance in the mechanisms of collagen degradation, which may be a deficiency in collagenase activity, a change in the susceptibility of the substrate, or a combination of both factors."}
{"id": "PMID:209695", "title": "Mechanism of cardiac output response to hypertonic sodium chloride infusion in dogs.", "content": "Hypertonic sodium chloride and tris(hydroxymethyl)amino-methane (Tris) hydrochloride (0.3 mmol/kg.min) were infused intravenously into chloralose-anesthetized dogs over a 20-min period. Cardiac output, maximum left ventricular dP/dt, and (dP/dt)/P increased by 55, 33, and 23%, respectively, during NaCl infusion, but Tris HCl infusion had no effects. NaCl infusion did not change heart rate or left ventricular end-diastolic pressure. Mean systemic and pulmonry arterial blood pressures increased, whereas total peripheral and pulmonary vascular resistances decreased. Responsiveness of cardiac beta-adrenergic receptors, as determined by serial intravenous injections of epinephrine, was not affected by NaCl infusion. Plasma catecholamine concentration, however, increased during NaCl infusion. In addition, the increases in cardiac output, maximum left ventricular dP/dt and (dP/dt)/P were abolished by prior treatment with practolol, a cardioselective beta-adrenergic receptor blocking agent. These results suggest that the hemodynamic effects of NaCl infusion were caused, at least in part, by the inotropic action of catecholamines.", "contents": "Mechanism of cardiac output response to hypertonic sodium chloride infusion in dogs. Hypertonic sodium chloride and tris(hydroxymethyl)amino-methane (Tris) hydrochloride (0.3 mmol/kg.min) were infused intravenously into chloralose-anesthetized dogs over a 20-min period. Cardiac output, maximum left ventricular dP/dt, and (dP/dt)/P increased by 55, 33, and 23%, respectively, during NaCl infusion, but Tris HCl infusion had no effects. NaCl infusion did not change heart rate or left ventricular end-diastolic pressure. Mean systemic and pulmonry arterial blood pressures increased, whereas total peripheral and pulmonary vascular resistances decreased. Responsiveness of cardiac beta-adrenergic receptors, as determined by serial intravenous injections of epinephrine, was not affected by NaCl infusion. Plasma catecholamine concentration, however, increased during NaCl infusion. In addition, the increases in cardiac output, maximum left ventricular dP/dt and (dP/dt)/P were abolished by prior treatment with practolol, a cardioselective beta-adrenergic receptor blocking agent. These results suggest that the hemodynamic effects of NaCl infusion were caused, at least in part, by the inotropic action of catecholamines."}
{"id": "PMID:209696", "title": "Epidemiological aspects of rotavirus infection in hospitalized Venezuelan children with gastroenteritis.", "content": "The prevalence of rotavirus infection in hospitalized Venezuelan children with gastroenteritis was studied during the period November 1975 to December 1976. Rotaviruses were the pathogens most frequently associated with gastroenteritis, being found in 121 of 293 (41.3%) patients and in only 3 of 66 (4.5%) controls. Other viruses (adenoviruses, enteroviruses, and small icosahedrical viruses) were detected at a lower frequency both in cases and controls. Rotaviruses were detected at a lower frequency both in cases and controls. Rotaviruses were readily detected throughout the year, which may correspond to the absence of seasonal temperature variation in a tropical country such as Venezuela. Children of all age groups examined (0-5 yr) were susceptible to rotavirus infection. The frequency of infection was slightly higher in the age group 13-24 mo, and significantly lower in children younger than 6 mo old. Rotaviruses were readily detected even after 12 days from the onset of illness. These results indicate that rotaviruses may be a major cause of infantile acute gastroenteritis in Venezuela.", "contents": "Epidemiological aspects of rotavirus infection in hospitalized Venezuelan children with gastroenteritis. The prevalence of rotavirus infection in hospitalized Venezuelan children with gastroenteritis was studied during the period November 1975 to December 1976. Rotaviruses were the pathogens most frequently associated with gastroenteritis, being found in 121 of 293 (41.3%) patients and in only 3 of 66 (4.5%) controls. Other viruses (adenoviruses, enteroviruses, and small icosahedrical viruses) were detected at a lower frequency both in cases and controls. Rotaviruses were detected at a lower frequency both in cases and controls. Rotaviruses were readily detected throughout the year, which may correspond to the absence of seasonal temperature variation in a tropical country such as Venezuela. Children of all age groups examined (0-5 yr) were susceptible to rotavirus infection. The frequency of infection was slightly higher in the age group 13-24 mo, and significantly lower in children younger than 6 mo old. Rotaviruses were readily detected even after 12 days from the onset of illness. These results indicate that rotaviruses may be a major cause of infantile acute gastroenteritis in Venezuela."}
{"id": "PMID:209697", "title": "New and old agents in diarrhea: a prospective study of an indigenous adult African population.", "content": "We conducted a prospective study 77 indigenous African adults with acute diarrhea seeking care at the major hospital in Nairobi, Kenya, to determine the major pathogens responsible for this syndrome in adults. Fecal and blood specimens were collected and examined for enteric bacterial pathogens, viruses, and parasites. In 13 (26%) inpatients and 11 (49%) outpatients Shigella was found, and heat-labile and heat-stable forms of enterotoxigenic Escherichia coli were found in 9 (18%) inpatients and 1 (4%) outpatient. Human revirus-like agent titers rose significantly in another 3 (6%). Amebic dysentery was not seen although hemagglutination-inhibition tests for invasive Entamoeba histolytica were positive in 4 inpatients. An etiologic agent was found in 65% of patients.", "contents": "New and old agents in diarrhea: a prospective study of an indigenous adult African population. We conducted a prospective study 77 indigenous African adults with acute diarrhea seeking care at the major hospital in Nairobi, Kenya, to determine the major pathogens responsible for this syndrome in adults. Fecal and blood specimens were collected and examined for enteric bacterial pathogens, viruses, and parasites. In 13 (26%) inpatients and 11 (49%) outpatients Shigella was found, and heat-labile and heat-stable forms of enterotoxigenic Escherichia coli were found in 9 (18%) inpatients and 1 (4%) outpatient. Human revirus-like agent titers rose significantly in another 3 (6%). Amebic dysentery was not seen although hemagglutination-inhibition tests for invasive Entamoeba histolytica were positive in 4 inpatients. An etiologic agent was found in 65% of patients."}
{"id": "PMID:209701", "title": "Ultrastructural changes of the early visceral yolk sac layer of mouse embryos after maternal injection of trypan blue.", "content": "The ultrastructural features of the early visceral yolk sac epithelium of normal mouse embryos on day 9 were compared to those whose mothers had received a single subcutaneous injection of 100mg/kg trypan blue on day 8. The following results were obtained: In normal embryos the visceral yolk sac cells are predominantly characterized by numerous membrane bounded inclusions localized in the supranuclear cytoplasm. In embryos of animals treated with trypan, blue, at about 12h after injection large single and only partly membrane bounded vacuoles are observed occupying most of the apical cytoplasm. Up to 24h after injection large cytoplasmic areas are seen which are in a stage of autodigestion possibly due to leakage of the vacuolar content. These alterations are exclusively limited to the visceral yolk sac epithelium whereas in the cells of the embryonic part, e.g. head process, no changes could be found. The observations are discussed in relation to the mechanism of the teratogenic activity of trypan blue.", "contents": "Ultrastructural changes of the early visceral yolk sac layer of mouse embryos after maternal injection of trypan blue. The ultrastructural features of the early visceral yolk sac epithelium of normal mouse embryos on day 9 were compared to those whose mothers had received a single subcutaneous injection of 100mg/kg trypan blue on day 8. The following results were obtained: In normal embryos the visceral yolk sac cells are predominantly characterized by numerous membrane bounded inclusions localized in the supranuclear cytoplasm. In embryos of animals treated with trypan, blue, at about 12h after injection large single and only partly membrane bounded vacuoles are observed occupying most of the apical cytoplasm. Up to 24h after injection large cytoplasmic areas are seen which are in a stage of autodigestion possibly due to leakage of the vacuolar content. These alterations are exclusively limited to the visceral yolk sac epithelium whereas in the cells of the embryonic part, e.g. head process, no changes could be found. The observations are discussed in relation to the mechanism of the teratogenic activity of trypan blue."}
{"id": "PMID:209706", "title": "Secretory antibody responses in cattle infected with foot-and-mouth disease virus.", "content": "Antibody responses in serum, saliva, nasal secretions, or esophageal-pharyngeal fluid of foot-and-mouth disease virus-infected steers were examined by single radial immunodiffusion and mouse-neutralization tests. In steers infected with type O foot-and-mouth disease virus, high serum antibody titers were detected within 10 days after infection. Antibody was first detected in saliva at 30 days and gradually increased to a plateau at about 90 days. Small amounts of antibody continued to be secreted in saliva and in nasal secretions for at least 6 months. Antibody was not detected in esophageal-pharyngeal fluid. The major antibody activity in secretions was due to secretory immunoglobulin A as revealed by radioimmunoelectrophoresis.", "contents": "Secretory antibody responses in cattle infected with foot-and-mouth disease virus. Antibody responses in serum, saliva, nasal secretions, or esophageal-pharyngeal fluid of foot-and-mouth disease virus-infected steers were examined by single radial immunodiffusion and mouse-neutralization tests. In steers infected with type O foot-and-mouth disease virus, high serum antibody titers were detected within 10 days after infection. Antibody was first detected in saliva at 30 days and gradually increased to a plateau at about 90 days. Small amounts of antibody continued to be secreted in saliva and in nasal secretions for at least 6 months. Antibody was not detected in esophageal-pharyngeal fluid. The major antibody activity in secretions was due to secretory immunoglobulin A as revealed by radioimmunoelectrophoresis."}
{"id": "PMID:209707", "title": "Natural mode of transmission of the bovine leukemia virus: role of bloodsucking insects.", "content": "The development of bovine leukemia virus (BLV) infection was studied in 14 noninfected young adult cattle exposed to 25 to 30 BLV-infected cows in an area of approximately 0.5 ha. Of 7 cattle (group 1) exposed beginning in July and August (midsummer) of 1976, 4 were infected by October, and all 7 by November (4 months' exposure). Of 7 cattle (group 2) exposed from February 1977 (midwinter), all remained negative for 3 months, and only 1 was positive after 6 months. By October 1977, however, 4 cattle in this group were infected, indicating that contact transmission of BLV is prevalent during the summer months. This, and the fact that BLV-infected lymphocytes were recovered from tabanids allowed to feed on a BLV-positive cow, supports the idea that bloodsucking insects play a major role in the spread of BLV.", "contents": "Natural mode of transmission of the bovine leukemia virus: role of bloodsucking insects. The development of bovine leukemia virus (BLV) infection was studied in 14 noninfected young adult cattle exposed to 25 to 30 BLV-infected cows in an area of approximately 0.5 ha. Of 7 cattle (group 1) exposed beginning in July and August (midsummer) of 1976, 4 were infected by October, and all 7 by November (4 months' exposure). Of 7 cattle (group 2) exposed from February 1977 (midwinter), all remained negative for 3 months, and only 1 was positive after 6 months. By October 1977, however, 4 cattle in this group were infected, indicating that contact transmission of BLV is prevalent during the summer months. This, and the fact that BLV-infected lymphocytes were recovered from tabanids allowed to feed on a BLV-positive cow, supports the idea that bloodsucking insects play a major role in the spread of BLV."}
{"id": "PMID:209710", "title": "Chemotherapy of advanced small-cell anaplastic carcinoma. Superiority of a four-drug combination to a three-drug combination.", "content": "A controlled clinical trial compared three-drug and four-drug combination chemotherapy in 109 patients with advanced small-cell anaplastic carcinoma of the lung. The combination of vincristine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cyclophosphamide, and methotrexate was significantly superior to the combination of the last three drugs alone with regard to median survival (230 versus 176 days) (P less than 0.01) and to duration of response (186 versus 112 days) (P less than 0.01). Objective response occurred in 78% and 75%, respectively. No significant difference in these values was observed in the comparison of the three subtypes of small-cell anaplastic carcinoma using the World Health Organization classification.", "contents": "Chemotherapy of advanced small-cell anaplastic carcinoma. Superiority of a four-drug combination to a three-drug combination. A controlled clinical trial compared three-drug and four-drug combination chemotherapy in 109 patients with advanced small-cell anaplastic carcinoma of the lung. The combination of vincristine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cyclophosphamide, and methotrexate was significantly superior to the combination of the last three drugs alone with regard to median survival (230 versus 176 days) (P less than 0.01) and to duration of response (186 versus 112 days) (P less than 0.01). Objective response occurred in 78% and 75%, respectively. No significant difference in these values was observed in the comparison of the three subtypes of small-cell anaplastic carcinoma using the World Health Organization classification."}
{"id": "PMID:209714", "title": "Adenoid cystic carcinoma with orbital and cranial metastases: case report.", "content": "Adenoid cystic carcinoma of the paranasal sinuses was demonstrated in a patient who subsequently developed a metastatic lesion to both orbits resulting in total blindness. While there are reports of extension of adenoid cystic carcinoma of the lacrimal gland to the adjacent orbit, this patient is an example of orbital extension of an adenoid cystic carcinoma of minor salivary gland originating in a paranasal sinus. The frequency and classification of this tumor also is reviewed.", "contents": "Adenoid cystic carcinoma with orbital and cranial metastases: case report. Adenoid cystic carcinoma of the paranasal sinuses was demonstrated in a patient who subsequently developed a metastatic lesion to both orbits resulting in total blindness. While there are reports of extension of adenoid cystic carcinoma of the lacrimal gland to the adjacent orbit, this patient is an example of orbital extension of an adenoid cystic carcinoma of minor salivary gland originating in a paranasal sinus. The frequency and classification of this tumor also is reviewed."}
{"id": "PMID:209715", "title": "[Blue rubber bleb naevus and glomangiomatosis, unicity or duality? About two cases (author's transl)].", "content": "About 2 personal cases, a review concerning Blue Rubber Bleb Naevus syndrome and glomangiomatosis is presented. Attention is drawn to the different histological pictures of these disease. Importance of a clear differentiation from the viewpoint of prognosis is emphasized.", "contents": "[Blue rubber bleb naevus and glomangiomatosis, unicity or duality? About two cases (author's transl)]. About 2 personal cases, a review concerning Blue Rubber Bleb Naevus syndrome and glomangiomatosis is presented. Attention is drawn to the different histological pictures of these disease. Importance of a clear differentiation from the viewpoint of prognosis is emphasized."}
{"id": "PMID:209712", "title": "[Formation of pseudotypes of VSV after culture in a human melanoma].", "content": "Electron microscope studies showed a high production of melanosomes and viral particles budding into the cisternae of the endoplasmic reticulum in cells derived from a subcutaneous metastasis. The history of this subline (HM6B-A) has been summarized elsewhere. An amelanotic subline (provided by the same patient) did not show similar virus particles. When infected with a vesicular stomatitis virus (VSV) thermolabile mutant (tl), these cells produced a VSV pseudotype in which a thermosensitive antigen was modified. Modification of surface VSV antigens was also detected by neutralisation tests. Using these tests, the VSV-pseudotype particles could be used as a tool to detect one or more antigens to a \"putative\" human melanomavirus, which might be only partially expressed.", "contents": "[Formation of pseudotypes of VSV after culture in a human melanoma]. Electron microscope studies showed a high production of melanosomes and viral particles budding into the cisternae of the endoplasmic reticulum in cells derived from a subcutaneous metastasis. The history of this subline (HM6B-A) has been summarized elsewhere. An amelanotic subline (provided by the same patient) did not show similar virus particles. When infected with a vesicular stomatitis virus (VSV) thermolabile mutant (tl), these cells produced a VSV pseudotype in which a thermosensitive antigen was modified. Modification of surface VSV antigens was also detected by neutralisation tests. Using these tests, the VSV-pseudotype particles could be used as a tool to detect one or more antigens to a \"putative\" human melanomavirus, which might be only partially expressed."}
{"id": "PMID:209723", "title": "Possible biochemical basis of memory disorder in Alzheimer disease.", "content": "Damage to the hippocampal formation, whether focal or diffuse, leads to severe impairment of short-term memory. The most common presenting symptom of Alzheimer disease is loss of short-term memory, and histologically the hippocampus is characteristically affected. Choline acetyltransferase, which is involved in the synthesis of acetylcholine, is depleted in the hippocampus in the disorder. Anticholinergic drugs administered to normal subjects can simulate some aspects of the memory defect seen in Alzheimer disease. It is postulated that damage to a cholinergic neuronal pathway running to or from the hippocampus underlies the memory disorder. This suggestion implies that it may be possible to improve memory in patients with Alzheimer disease by pharmacological means.", "contents": "Possible biochemical basis of memory disorder in Alzheimer disease. Damage to the hippocampal formation, whether focal or diffuse, leads to severe impairment of short-term memory. The most common presenting symptom of Alzheimer disease is loss of short-term memory, and histologically the hippocampus is characteristically affected. Choline acetyltransferase, which is involved in the synthesis of acetylcholine, is depleted in the hippocampus in the disorder. Anticholinergic drugs administered to normal subjects can simulate some aspects of the memory defect seen in Alzheimer disease. It is postulated that damage to a cholinergic neuronal pathway running to or from the hippocampus underlies the memory disorder. This suggestion implies that it may be possible to improve memory in patients with Alzheimer disease by pharmacological means."}
{"id": "PMID:209724", "title": "Failure to demonstrate papovavirus tumor antigen in human cerebral neoplasms.", "content": "Cell cultures derived from 80 brain tumors failed to show the intranuclear tumor (T) antigen common to cells transformed by simian virus 40 (SV40) or BK or JC viruses.", "contents": "Failure to demonstrate papovavirus tumor antigen in human cerebral neoplasms. Cell cultures derived from 80 brain tumors failed to show the intranuclear tumor (T) antigen common to cells transformed by simian virus 40 (SV40) or BK or JC viruses."}
{"id": "PMID:209725", "title": "Leigh's disease in an adult with evidence of \"inhibitor factor\" in family members.", "content": "A 21-year-old man with a longstanding history of impaired visual acuity, strabismus, broad-based gait, and below-average intellectual capacity developed respiratory difficulties and intermittent generalized weakness at age 19. He subsequently showed signs of massive brainstem dysfunction and died. Postmortem examination demonstrated changes compatible with subacute necrotizing encephalomyelopathy of Leigh involving portions of the diencephalon, midbrain, pons, and medulla as well as portions of the spinal cord and optic nerves. Evaluation of family members for presence of the urinary inhibitor factor for thiamine diphosphate phosphoryl transferase revealed abnormal levels in a brother, a maternal uncle, and the maternal grandfather of the patient.", "contents": "Leigh's disease in an adult with evidence of \"inhibitor factor\" in family members. A 21-year-old man with a longstanding history of impaired visual acuity, strabismus, broad-based gait, and below-average intellectual capacity developed respiratory difficulties and intermittent generalized weakness at age 19. He subsequently showed signs of massive brainstem dysfunction and died. Postmortem examination demonstrated changes compatible with subacute necrotizing encephalomyelopathy of Leigh involving portions of the diencephalon, midbrain, pons, and medulla as well as portions of the spinal cord and optic nerves. Evaluation of family members for presence of the urinary inhibitor factor for thiamine diphosphate phosphoryl transferase revealed abnormal levels in a brother, a maternal uncle, and the maternal grandfather of the patient."}
{"id": "PMID:209728", "title": "Proteins that affect DNA conformation.", "content": "In eucaryotic cells virtually all of the DNA is complex with proteins to form a unit fiber approximately 100 A in diameter. Chromatin is formed by the higher order coiling of the unit fiber. In procaryotic cells, as exemplified by E. coli, the actual structure of the chromosome is less clear (218), but the discovery of the DNA gyrase raises the possibility that the DNA helix in the cell is maintained in an underwound state. It may be important to consider these structural features of DNA in future biochemical studies on replication, transcription, and recombination. The recent discoveries of the DNA swivelases, the DNA gyrase, and the DNA unwinding enzymes considerably increase our knowledge of DNA biochemistry. As more is learned about these enzymes and their interaction with DNA, the prospects for understanding the details of DNA transcription, DNA recombination, and particularly DNA replication appear to be good.", "contents": "Proteins that affect DNA conformation. In eucaryotic cells virtually all of the DNA is complex with proteins to form a unit fiber approximately 100 A in diameter. Chromatin is formed by the higher order coiling of the unit fiber. In procaryotic cells, as exemplified by E. coli, the actual structure of the chromosome is less clear (218), but the discovery of the DNA gyrase raises the possibility that the DNA helix in the cell is maintained in an underwound state. It may be important to consider these structural features of DNA in future biochemical studies on replication, transcription, and recombination. The recent discoveries of the DNA swivelases, the DNA gyrase, and the DNA unwinding enzymes considerably increase our knowledge of DNA biochemistry. As more is learned about these enzymes and their interaction with DNA, the prospects for understanding the details of DNA transcription, DNA recombination, and particularly DNA replication appear to be good."}
{"id": "PMID:209734", "title": "[Comparative analysis of the action of an interferon inducer in in vitro and in vivo systems].", "content": "Investigation of interferon inductor (poly IC) in vitro (chick embryon fibroblasts) and in vivo (mice) showed that the main parameters of the preparation effect, i. e. induction of interferon and development of resistance to viruses are as a whole quite comparable. The phenomenon of hyporeactivity in the both systems was reproduced on repeated use of the inductor. At the same time significant differences in the stimulating effect of DEAE-dextran were registered. The merits and demerits of the in vitro system for using in studies on antiviral drugs of the above type are discussed.", "contents": "[Comparative analysis of the action of an interferon inducer in in vitro and in vivo systems]. Investigation of interferon inductor (poly IC) in vitro (chick embryon fibroblasts) and in vivo (mice) showed that the main parameters of the preparation effect, i. e. induction of interferon and development of resistance to viruses are as a whole quite comparable. The phenomenon of hyporeactivity in the both systems was reproduced on repeated use of the inductor. At the same time significant differences in the stimulating effect of DEAE-dextran were registered. The merits and demerits of the in vitro system for using in studies on antiviral drugs of the above type are discussed."}
{"id": "PMID:209736", "title": "Antiviral effect of commercial juices and beverages.", "content": "Nineteen commercial juices or beverages were tested for inactivation of poliovirus type 1. Grape and apple juices and tea were particularly antiviral. Although antiviral in aqueous solution, ascorbic acid was ineffective after addition to juices.", "contents": "Antiviral effect of commercial juices and beverages. Nineteen commercial juices or beverages were tested for inactivation of poliovirus type 1. Grape and apple juices and tea were particularly antiviral. Although antiviral in aqueous solution, ascorbic acid was ineffective after addition to juices."}
{"id": "PMID:209754", "title": "Mechanism of nicotine-induced release of norepinephrine from adrenergic nerve endings: is generation and propagation of impulses necessary?", "content": "The mechanism of release of 3H-norepinephrine (3H-NE) from adrenergic nerve endings by nicotine was investigated. Tetrodotoxin (5 X 10(-7) g/ml) abolished the contractile response of adrenergically innervated tissues, namely, rat isolated vas deferens, cat splenic strips, guinea-pig atria to transmural stimulation but not to nicotinic agents, and it did not affect the release of 3H-NE by nicotine from rat isolated vas deferens. Incubation of tissues in low Na+ (23 mM) and high K+ (50 mM) medium, which is known to inhibit propagation of nerve impulses, did not affect the nicotine-induced outflow of 3H-NE. These observations support the contention that the generation of action potential in the postganglionic sympathetic nerve fibres is not the cause of release of norepinephrine by nicotinic agents.", "contents": "Mechanism of nicotine-induced release of norepinephrine from adrenergic nerve endings: is generation and propagation of impulses necessary? The mechanism of release of 3H-norepinephrine (3H-NE) from adrenergic nerve endings by nicotine was investigated. Tetrodotoxin (5 X 10(-7) g/ml) abolished the contractile response of adrenergically innervated tissues, namely, rat isolated vas deferens, cat splenic strips, guinea-pig atria to transmural stimulation but not to nicotinic agents, and it did not affect the release of 3H-NE by nicotine from rat isolated vas deferens. Incubation of tissues in low Na+ (23 mM) and high K+ (50 mM) medium, which is known to inhibit propagation of nerve impulses, did not affect the nicotine-induced outflow of 3H-NE. These observations support the contention that the generation of action potential in the postganglionic sympathetic nerve fibres is not the cause of release of norepinephrine by nicotinic agents."}
{"id": "PMID:209756", "title": "Late onset of fatal cytomegalovirus infection after renal transplantation. Primary or reactivation infection?", "content": "Cytomegaloviurs (CMV) infections are a recognized problem in the first six months after renal transplantation. Studies have suggested that primary infections produce symptomatic disease, whereas reactivation infections are usually asymptomatic. Two patients are described who developed fatal CMV infections in the second year after transplantation. Both patients had typical CMV disease with fever, pneumonitis, and hepatitis. Results of serologic studies in one patient were characteristic of primary infection, with seroconversion at the time of disease and appearance of specific IgM antibodies.  The other patient had a similar antibody response at the time of his illness, but serial antibody tests showed that he had had a transient seroconversion earlier, in the second month after transplanation, that was not associated with clinical symptoms. These patients indicate that CMV infection must be considered in the differential diagnosis of serious febrile illnesses even in the late posttransplantation period and may occur either as the result of primary or reactivation infection. Serologic studies at the time of illness may not allow distinction between the types of infection.", "contents": "Late onset of fatal cytomegalovirus infection after renal transplantation. Primary or reactivation infection? Cytomegaloviurs (CMV) infections are a recognized problem in the first six months after renal transplantation. Studies have suggested that primary infections produce symptomatic disease, whereas reactivation infections are usually asymptomatic. Two patients are described who developed fatal CMV infections in the second year after transplantation. Both patients had typical CMV disease with fever, pneumonitis, and hepatitis. Results of serologic studies in one patient were characteristic of primary infection, with seroconversion at the time of disease and appearance of specific IgM antibodies.  The other patient had a similar antibody response at the time of his illness, but serial antibody tests showed that he had had a transient seroconversion earlier, in the second month after transplanation, that was not associated with clinical symptoms. These patients indicate that CMV infection must be considered in the differential diagnosis of serious febrile illnesses even in the late posttransplantation period and may occur either as the result of primary or reactivation infection. Serologic studies at the time of illness may not allow distinction between the types of infection."}
{"id": "PMID:209757", "title": "Endorphins in psychiatry: an overview and a hypothesis.", "content": "This article presents an overview of the biochemistry, pharmacology, and physiology of endogenous opioid peptides (endorphins). Clinical psychopharmacology of exogenous opiate agonists and antagonists is reviewed. The evidence presented in the review is compatible with a hypothesis that the level of functional endorphins may be related to psychological events, with a normal level needed for psychological homeostasis. One corollary of this hypothesis is that the level of opioids in the brains of the mentally ill may be disturbed. Therapeutic implications of this hypothesis are considered.", "contents": "Endorphins in psychiatry: an overview and a hypothesis. This article presents an overview of the biochemistry, pharmacology, and physiology of endogenous opioid peptides (endorphins). Clinical psychopharmacology of exogenous opiate agonists and antagonists is reviewed. The evidence presented in the review is compatible with a hypothesis that the level of functional endorphins may be related to psychological events, with a normal level needed for psychological homeostasis. One corollary of this hypothesis is that the level of opioids in the brains of the mentally ill may be disturbed. Therapeutic implications of this hypothesis are considered."}
{"id": "PMID:209758", "title": "Peptides and psychoneuroendocrinology. A perspective.", "content": "Research indicates that brain peptides exert both behavioral and endocrinologic effects in humans and animals. This review summarizes the best known behavioral actions of four endogenous peptides: luteinizing hormone-releasing hormone (LHRH), adrenocorticotrophic hormone (ACTH), vasopressin, and angiotensin. The hypothalamic-releasing hormones play a role in modulating pituitary-end organ systems. Behavioral disorders may, in the future, be susceptible to formulation in terms of changes in brain peptides. Peptide research in psychiatry may be approached in several ways.", "contents": "Peptides and psychoneuroendocrinology. A perspective. Research indicates that brain peptides exert both behavioral and endocrinologic effects in humans and animals. This review summarizes the best known behavioral actions of four endogenous peptides: luteinizing hormone-releasing hormone (LHRH), adrenocorticotrophic hormone (ACTH), vasopressin, and angiotensin. The hypothalamic-releasing hormones play a role in modulating pituitary-end organ systems. Behavioral disorders may, in the future, be susceptible to formulation in terms of changes in brain peptides. Peptide research in psychiatry may be approached in several ways."}
{"id": "PMID:209760", "title": "[Clinical endocrine investigations in patients with pituitary adenoma (author's transl)].", "content": "LH-RH tests of hypothalamo-pituitary gonadotropinfunction were performed in 26 patients with pituitary adenomata before and after prolactin suppression and/or surgical treatment. Various degrees of galactorrhea together with menstrual disorders were the key symptoms in all patients. There was a significant association of elevated prolactin levels with impaired LH-responses. Seven patients have undergone transspenoidal dissection of the pituitary adenoma and in five of them the pituitary LH-response reverted to normal (R2) after surgery. Nine of 15 amenorrhoic patients had a recurrence of menstrual cyclicity, partly biphasic within 3 months and a normalized LH-response after Bromocriptin therapy. 19 of our patients were desirous of pregnancy. Five pregnancies were confirmed within 4 months of treatment.", "contents": "[Clinical endocrine investigations in patients with pituitary adenoma (author's transl)]. LH-RH tests of hypothalamo-pituitary gonadotropinfunction were performed in 26 patients with pituitary adenomata before and after prolactin suppression and/or surgical treatment. Various degrees of galactorrhea together with menstrual disorders were the key symptoms in all patients. There was a significant association of elevated prolactin levels with impaired LH-responses. Seven patients have undergone transspenoidal dissection of the pituitary adenoma and in five of them the pituitary LH-response reverted to normal (R2) after surgery. Nine of 15 amenorrhoic patients had a recurrence of menstrual cyclicity, partly biphasic within 3 months and a normalized LH-response after Bromocriptin therapy. 19 of our patients were desirous of pregnancy. Five pregnancies were confirmed within 4 months of treatment."}
{"id": "PMID:209761", "title": "Species difference in the secretory response to dopamine in the pancreas of dogs, cats, rabbits and rats.", "content": "The effects of dopamine and L-dopa on the exocrine secretion of the pancreas were compared in rats, cats, rabbits and dogs. Dopamine and its precursor, L-dopa, induced a secretin-like stimulation in dogs, while their effects were significantly less in rats. The dopaminergic receptor stimulus was involved in the exocrine secretion of the pancreas in dogs, whereas in rats, the beta-adrenergic receptor was involved. Spontaneous secretion in the resting state was present in rabbits but absent in cats. This spontaneous secretion in rabbits could be definitely inhibited by either dopamine or L-dopa. The secretin-induced secretion in both rabbits and cats was markedly inhibited by either dopamine or L-dopa. Species difference in the secretory response to dopamine in the pancreas of dogs, cats, rabbits and rats may be ascribed to the difference in the incorporation of exogenous L-dopa and dopamine in the exocrine cells of the pancreas.", "contents": "Species difference in the secretory response to dopamine in the pancreas of dogs, cats, rabbits and rats. The effects of dopamine and L-dopa on the exocrine secretion of the pancreas were compared in rats, cats, rabbits and dogs. Dopamine and its precursor, L-dopa, induced a secretin-like stimulation in dogs, while their effects were significantly less in rats. The dopaminergic receptor stimulus was involved in the exocrine secretion of the pancreas in dogs, whereas in rats, the beta-adrenergic receptor was involved. Spontaneous secretion in the resting state was present in rabbits but absent in cats. This spontaneous secretion in rabbits could be definitely inhibited by either dopamine or L-dopa. The secretin-induced secretion in both rabbits and cats was markedly inhibited by either dopamine or L-dopa. Species difference in the secretory response to dopamine in the pancreas of dogs, cats, rabbits and rats may be ascribed to the difference in the incorporation of exogenous L-dopa and dopamine in the exocrine cells of the pancreas."}
{"id": "PMID:209762", "title": "Morphological and morphometric studies on the terminal boutons on the neurosecretory cells of the rat paraventricular nucleus.", "content": "Ultrathin sections of the male rat hypothalamus, including the paraventricular nucleus prepared by perfusion fixation, were observed with a transmission electron microscope. The neurosecretory cells were classified into four types based on the difference in the structures of cell organelles and in the number and appearance of secretory granules present. This was reported elsewhere (Yukitake et al. Cell Tis. Res. 177: 1-8, 1977). Morphological and morphometric analyses on the terminal boutons abutting on the surface of the neursecretory cells were performed. The boutons were classified into three types: first type, having only small clear vesicles; second type, having large cored vesicles; and third type, having closely packed small vesicles. The incidence of the occurrence of each type of terminal bouton as well as the ratios of the surface of the perikarya of the neurosecretory cells covered by the terminal boutons were almost constant in all types of neurosecretory cells. As the stage of the secretory cycle proceeded, the numerical densities of the small synaptic vesicles in the terminal boutons clearly decreased. These results were consistent with the idea that each type of neurosecretory cell represented a different stage in the cell specific secretory cycle rather than a difference in neuron grouping, and that the terminal boutons probably transmitted some information regulating the secretory function of the cells.", "contents": "Morphological and morphometric studies on the terminal boutons on the neurosecretory cells of the rat paraventricular nucleus. Ultrathin sections of the male rat hypothalamus, including the paraventricular nucleus prepared by perfusion fixation, were observed with a transmission electron microscope. The neurosecretory cells were classified into four types based on the difference in the structures of cell organelles and in the number and appearance of secretory granules present. This was reported elsewhere (Yukitake et al. Cell Tis. Res. 177: 1-8, 1977). Morphological and morphometric analyses on the terminal boutons abutting on the surface of the neursecretory cells were performed. The boutons were classified into three types: first type, having only small clear vesicles; second type, having large cored vesicles; and third type, having closely packed small vesicles. The incidence of the occurrence of each type of terminal bouton as well as the ratios of the surface of the perikarya of the neurosecretory cells covered by the terminal boutons were almost constant in all types of neurosecretory cells. As the stage of the secretory cycle proceeded, the numerical densities of the small synaptic vesicles in the terminal boutons clearly decreased. These results were consistent with the idea that each type of neurosecretory cell represented a different stage in the cell specific secretory cycle rather than a difference in neuron grouping, and that the terminal boutons probably transmitted some information regulating the secretory function of the cells."}
{"id": "PMID:209763", "title": "GABA in pancreatic islets.", "content": "A high concentration of gamma-aminobutyric acid (GABA) and a high activity of glutamate decarboxylase (GAD), enzyme for GABA synthesis, were demonstrated in the rat pancreatic islets using a recently developed assay method combining the GABase system with the enzymatic NADP-NADPH cyclin method. Both GABA concentration and GAD activity in the pancreatic islets were comparable to those in the central nervous system (CNS). An insulinoma consisting mainly of B cells possessed a high concentration of GABA and a high activity of GAD. On the other hand, in the pancreatic islets of rats after treatment with streptozotocin, a specific attacker of B cells, GABA was negligible in amount. The occurrence of GABA in the pancreatic islets, at least B cells, apparently supports the view of Fujita that the islet cells are paraneurons. Presence of exogenous GABA does not influence the glucose- and amino acid-induced insulin release. The uptake of 3H-GABA into the pancreatic islet was small in amount as compared with that into the brain tissue such as the substantia nigra. These observations suggest that the different compartmentation of GABA in the islets from that in the CNS.", "contents": "GABA in pancreatic islets. A high concentration of gamma-aminobutyric acid (GABA) and a high activity of glutamate decarboxylase (GAD), enzyme for GABA synthesis, were demonstrated in the rat pancreatic islets using a recently developed assay method combining the GABase system with the enzymatic NADP-NADPH cyclin method. Both GABA concentration and GAD activity in the pancreatic islets were comparable to those in the central nervous system (CNS). An insulinoma consisting mainly of B cells possessed a high concentration of GABA and a high activity of GAD. On the other hand, in the pancreatic islets of rats after treatment with streptozotocin, a specific attacker of B cells, GABA was negligible in amount. The occurrence of GABA in the pancreatic islets, at least B cells, apparently supports the view of Fujita that the islet cells are paraneurons. Presence of exogenous GABA does not influence the glucose- and amino acid-induced insulin release. The uptake of 3H-GABA into the pancreatic islet was small in amount as compared with that into the brain tissue such as the substantia nigra. These observations suggest that the different compartmentation of GABA in the islets from that in the CNS."}
{"id": "PMID:209765", "title": "Early signs of oral and inhalative cadmium uptake in rats.", "content": "Female wistar rats, 170--190 g, were exposed for 90 days to cadmium oxide aerosols containing 25 and 50 microgram Cd/m3 and for 63 days to 100 microgram Cd/m3. Simultaneously female wistar rats, 170--190 g, were fed 25, 50, and 100 ppm cadmium in drinking water for 90 days. After inhalation and ingestion of the metal, there were comparable kidney cadmium levels, but higher liver and blood levels after oral uptake. Coincident with the higher blood cadmium concentrations, proteinuria was observed only after oral administration. Likewise, there was a significant decrease of serum iron after ingestion and no lowering of the serum iron after inhalation of the metal. The inhalation led to a marked dose dependent weight increase of the lungs, which was followed by an impairment of gas exchange. Obviously, after inhalative cadmium uptake of 90 days pulmonary changes precede renal damage.", "contents": "Early signs of oral and inhalative cadmium uptake in rats. Female wistar rats, 170--190 g, were exposed for 90 days to cadmium oxide aerosols containing 25 and 50 microgram Cd/m3 and for 63 days to 100 microgram Cd/m3. Simultaneously female wistar rats, 170--190 g, were fed 25, 50, and 100 ppm cadmium in drinking water for 90 days. After inhalation and ingestion of the metal, there were comparable kidney cadmium levels, but higher liver and blood levels after oral uptake. Coincident with the higher blood cadmium concentrations, proteinuria was observed only after oral administration. Likewise, there was a significant decrease of serum iron after ingestion and no lowering of the serum iron after inhalation of the metal. The inhalation led to a marked dose dependent weight increase of the lungs, which was followed by an impairment of gas exchange. Obviously, after inhalative cadmium uptake of 90 days pulmonary changes precede renal damage."}
{"id": "PMID:209767", "title": "Stimulation of antibodies to Epstein-Barr virus (EBV) in acute viral infections.", "content": "Acute and convalescent sera from 77 patients with serologically confirmed influenza, measles and adenovirus infections and from 36 healthy controls were tested for the level of antibodies to Epstein-Barr (EB) virus. In  the three groups of patients significantly higher titers of antibodies to EB viral capsid antigen (VCA) were found as compared to the controls. In 19 patients twofold or higher rise in antibody titers between the first and second blood sample was demonstrated. It is suggested that in patients with influenza, measles or adenovirus infections, involvement of lymphocytes leads to reactivation of EB virus and antibody formation is stimulated.", "contents": "Stimulation of antibodies to Epstein-Barr virus (EBV) in acute viral infections. Acute and convalescent sera from 77 patients with serologically confirmed influenza, measles and adenovirus infections and from 36 healthy controls were tested for the level of antibodies to Epstein-Barr (EB) virus. In  the three groups of patients significantly higher titers of antibodies to EB viral capsid antigen (VCA) were found as compared to the controls. In 19 patients twofold or higher rise in antibody titers between the first and second blood sample was demonstrated. It is suggested that in patients with influenza, measles or adenovirus infections, involvement of lymphocytes leads to reactivation of EB virus and antibody formation is stimulated."}
{"id": "PMID:209768", "title": "Gel double immunodiffusion studies with sex human rhinoviruses.", "content": "Rabbits were immunized on six occasions during a seven month period with fluorocarbon and sucrose denstiy gradient purified preparations of human rhinovirus types 1A,2,3,4,9, OR 14. Sera collected 1 week after the final immunization formed 1 or 2 preciptin lines when reacted by immunodiffusion against fluorocarbon purified preparations of each homologous immunizing virus. Heterologous preciptin cross reactions were detected between: RV1A antigen and rabbit sera to RV2, RV9 and RV14; RV2 antigen and sera to RV1A; RV14 antigen and sera to RV3. The heterologous \"group\" or C-antigenic nature of the cross reactions was suggested by the merging of heterologous preciptin lines formed against rabbit sera with \"group\" antibody preciptin lines formed against human sera and by the location of heterologous reaction close to the antigen well. In addition, the presence of C-antigenic particles in the fluorocarbon treated RV2 preparation was suggested by the demonstration that a subpopulation of viral particles migrated to a pH of 4.4 by isoelectric focusing.", "contents": "Gel double immunodiffusion studies with sex human rhinoviruses. Rabbits were immunized on six occasions during a seven month period with fluorocarbon and sucrose denstiy gradient purified preparations of human rhinovirus types 1A,2,3,4,9, OR 14. Sera collected 1 week after the final immunization formed 1 or 2 preciptin lines when reacted by immunodiffusion against fluorocarbon purified preparations of each homologous immunizing virus. Heterologous preciptin cross reactions were detected between: RV1A antigen and rabbit sera to RV2, RV9 and RV14; RV2 antigen and sera to RV1A; RV14 antigen and sera to RV3. The heterologous \"group\" or C-antigenic nature of the cross reactions was suggested by the merging of heterologous preciptin lines formed against rabbit sera with \"group\" antibody preciptin lines formed against human sera and by the location of heterologous reaction close to the antigen well. In addition, the presence of C-antigenic particles in the fluorocarbon treated RV2 preparation was suggested by the demonstration that a subpopulation of viral particles migrated to a pH of 4.4 by isoelectric focusing."}
{"id": "PMID:209769", "title": "Cell cycle-dependent multiplication of avian adenoviruses in chicken embryo fibroblasts.", "content": "Propagation of CELO virus employing confluent monolayers of chicken enbryo fibroblasts (CEF) yielded virus titers one to two logs lower than those from confluent chicken kidney (CK) cells. An enhancement of virus production in CEF as measured by plaque formation was obtainedby infectng cultures in the growing non confluent state. Measurements of 3H-thymidine incorporation revealed a positive correlation between the DNA synthesis of CEF cultures at the time of inoculation and the amount of progeny virus, whereas  in the CK-CELO-system no such relation was observed. Requirement of replicative fibroblasts for CELO multiplication was also demonstrated by comparison of virus replication in synchronized stationary and serum stimulated CEF cells. In stationary CEF cells arrested in the G1 phase of the cell replication cycle by serum deprivation and infected withe CELO virs, no cytopathic effect could be observed, and only very low amounts of virus were produced. But 24 hours after release of these cells for growth by serum stimulation a logarithmic rate of virus multiplication and a complete CPE occurred. Infection of synchronized CEF cultures at different stages of the cell cycle revealed that CELO multiplication was correlated with the S phase of the infected cell. In synchronized CELO infected CEF cultures viral DNA synthesis started 12 to 14 hours after growth stimulation when cells were near the end of the S phase. In contrast, no viral DNA synthesis could be measured in growth arrested CELO infected CEF cells, when cellular DNA synthesis was low. Therefore not only production of infectious virus but also viral DNA synthesis is correlated with events during the S phase of the infected CEF cell.", "contents": "Cell cycle-dependent multiplication of avian adenoviruses in chicken embryo fibroblasts. Propagation of CELO virus employing confluent monolayers of chicken enbryo fibroblasts (CEF) yielded virus titers one to two logs lower than those from confluent chicken kidney (CK) cells. An enhancement of virus production in CEF as measured by plaque formation was obtainedby infectng cultures in the growing non confluent state. Measurements of 3H-thymidine incorporation revealed a positive correlation between the DNA synthesis of CEF cultures at the time of inoculation and the amount of progeny virus, whereas  in the CK-CELO-system no such relation was observed. Requirement of replicative fibroblasts for CELO multiplication was also demonstrated by comparison of virus replication in synchronized stationary and serum stimulated CEF cells. In stationary CEF cells arrested in the G1 phase of the cell replication cycle by serum deprivation and infected withe CELO virs, no cytopathic effect could be observed, and only very low amounts of virus were produced. But 24 hours after release of these cells for growth by serum stimulation a logarithmic rate of virus multiplication and a complete CPE occurred. Infection of synchronized CEF cultures at different stages of the cell cycle revealed that CELO multiplication was correlated with the S phase of the infected cell. In synchronized CELO infected CEF cultures viral DNA synthesis started 12 to 14 hours after growth stimulation when cells were near the end of the S phase. In contrast, no viral DNA synthesis could be measured in growth arrested CELO infected CEF cells, when cellular DNA synthesis was low. Therefore not only production of infectious virus but also viral DNA synthesis is correlated with events during the S phase of the infected CEF cell."}
{"id": "PMID:209770", "title": "Effect of treatment with certain flavonoids on Mengo virus-induced encephalitis in mice.", "content": "Among the four flavonoids tested quercetin and morin proved to be significantly effective against lethal Mengo virus-induced encephalitis in mice when the drugs were adminsitered orally (p.o.). With subcutaneous (s.c.) administration all four drugs failed to prevent mortality in the infected mice. Quercetin produced maximum protective response in intraperitoneally (i.p.) or intranasally (i.nas.) infected mice when administered twice daily at doses of 20 mg/kg for a period of not less than four days. Single injections of the full daily dose of drug failed to prevent deaths in mice. Treatment must be begun at the time of, or prior to, virus inoculation. Delayed initiation of treatment was ineffective in preventing mortality.", "contents": "Effect of treatment with certain flavonoids on Mengo virus-induced encephalitis in mice. Among the four flavonoids tested quercetin and morin proved to be significantly effective against lethal Mengo virus-induced encephalitis in mice when the drugs were adminsitered orally (p.o.). With subcutaneous (s.c.) administration all four drugs failed to prevent mortality in the infected mice. Quercetin produced maximum protective response in intraperitoneally (i.p.) or intranasally (i.nas.) infected mice when administered twice daily at doses of 20 mg/kg for a period of not less than four days. Single injections of the full daily dose of drug failed to prevent deaths in mice. Treatment must be begun at the time of, or prior to, virus inoculation. Delayed initiation of treatment was ineffective in preventing mortality."}
{"id": "PMID:209771", "title": "[Submicroscopical study of the granule-containing cells of bronchial carcinoids].", "content": "The submicroscopical structure of three bronchial carcinoids was studied. In all the cases, in the cytoplasm of tumor cells secretory granules formed from cisterns of the Golgi apparatus were found. Two types of granules were observed. The first ones were from 150 to 250 nm in size, the second--from 400 to 600 nm. Granules less than 500 nm in size comprise about 90% and cannot be observed by light microscopy because of the low resolving power of the microscope. It is suggested that the secretory product is eliminated by diffusion through the granular and then plasma membrane. The granules are assumed to be heterogeneous in their chemical composition. Secretion of other compounds in addition to serotonin is presumed. The ultrastructural similarity of the tumor cells and Kulchitsky cells is no proof of theif histogenetic relationship.", "contents": "[Submicroscopical study of the granule-containing cells of bronchial carcinoids]. The submicroscopical structure of three bronchial carcinoids was studied. In all the cases, in the cytoplasm of tumor cells secretory granules formed from cisterns of the Golgi apparatus were found. Two types of granules were observed. The first ones were from 150 to 250 nm in size, the second--from 400 to 600 nm. Granules less than 500 nm in size comprise about 90% and cannot be observed by light microscopy because of the low resolving power of the microscope. It is suggested that the secretory product is eliminated by diffusion through the granular and then plasma membrane. The granules are assumed to be heterogeneous in their chemical composition. Secretion of other compounds in addition to serotonin is presumed. The ultrastructural similarity of the tumor cells and Kulchitsky cells is no proof of theif histogenetic relationship."}
{"id": "PMID:209772", "title": "Epstein-Barr virus-associated antigens in nasopharyngeal carcinoma.", "content": "Thirty-five sera from American patients with nasopharyngeal carcinoma were examined for Epstein-Barr virus (EBV)-associated antigens and compared with 85 sera from patients with other head and neck cancers, 80 sera from patients with lymphoma, and 47 sera from healthy control subjects. There was a definite correlation between the presence of nasopharyngeal carcinoma and the level of antibody titers to EBV. In particular, two tests that detected antibody to early antigen and antibody to viral capsid antigen in the serum IgA fraction were highly specific for the presence of nasopharyngeal carcinoma. There was a significant decrease in these antibody titers with clinical remission of the disease in treated patients with nasopharyngeal carcinoma. Clinically, these tests should have important application in the management and follow-up of patients with nasopharyngeal carcinoma.", "contents": "Epstein-Barr virus-associated antigens in nasopharyngeal carcinoma. Thirty-five sera from American patients with nasopharyngeal carcinoma were examined for Epstein-Barr virus (EBV)-associated antigens and compared with 85 sera from patients with other head and neck cancers, 80 sera from patients with lymphoma, and 47 sera from healthy control subjects. There was a definite correlation between the presence of nasopharyngeal carcinoma and the level of antibody titers to EBV. In particular, two tests that detected antibody to early antigen and antibody to viral capsid antigen in the serum IgA fraction were highly specific for the presence of nasopharyngeal carcinoma. There was a significant decrease in these antibody titers with clinical remission of the disease in treated patients with nasopharyngeal carcinoma. Clinically, these tests should have important application in the management and follow-up of patients with nasopharyngeal carcinoma."}
{"id": "PMID:209773", "title": "Cellular mixed tumors of the salivary glands.", "content": "Mixed tumors are unusual in that they possess both epithelial and mesenchymal elements. The proportions of the two elements vary greatly; the lesions with a pronounced preponderance of epithelial tissue have been called cellular mixed tumors. This increase in epithelial cellularity often results in misdiagnosis or in concern that the tumor may be more aggressive than the ordinary mixed tumor--possibly even malignant. We have reviewed 1,095 consecutive parotid tumors that were removed at the Mayo Clinic, Rochester, Minn, from 1950 through 1970. Ninety-three of the lesions were diagnosed initially as cellular mixed tumors, and slides were available for review. Of these 93, 43 fulfilled our criteria of having greater than 80% of each tumor composed of the packed epithelial cells. All tumors had a corresponding reduction in the mesenchymal portion. The records of the 43 patients were studied to determine the clinical behavior of these neoplasms, particularly with regard to recurrence, metastasis, and malignant transformation. Our findings confirmed our clinical suspicions that some of these cellular mixed tumors, notably those that showed histopathologic evidence of an increased rate of mitotic activity, can and do act in a more aggressive manner.", "contents": "Cellular mixed tumors of the salivary glands. Mixed tumors are unusual in that they possess both epithelial and mesenchymal elements. The proportions of the two elements vary greatly; the lesions with a pronounced preponderance of epithelial tissue have been called cellular mixed tumors. This increase in epithelial cellularity often results in misdiagnosis or in concern that the tumor may be more aggressive than the ordinary mixed tumor--possibly even malignant. We have reviewed 1,095 consecutive parotid tumors that were removed at the Mayo Clinic, Rochester, Minn, from 1950 through 1970. Ninety-three of the lesions were diagnosed initially as cellular mixed tumors, and slides were available for review. Of these 93, 43 fulfilled our criteria of having greater than 80% of each tumor composed of the packed epithelial cells. All tumors had a corresponding reduction in the mesenchymal portion. The records of the 43 patients were studied to determine the clinical behavior of these neoplasms, particularly with regard to recurrence, metastasis, and malignant transformation. Our findings confirmed our clinical suspicions that some of these cellular mixed tumors, notably those that showed histopathologic evidence of an increased rate of mitotic activity, can and do act in a more aggressive manner."}
{"id": "PMID:209774", "title": "Synovial sarcoma of the neck associated with previous head and neck radiation therapy.", "content": "Synovial sarcoma is a rare neoplasm that uncommonly arises in the neck. Fourteen years after facial and neck radiation therapy for acne, synovial sarcoma of the neck developed in a young man. Possible radiation-induced benign and malignant neoplasms that arise in the head and neck region, either of thyroid or extrathyroid origin, remain a continuing medical problem.", "contents": "Synovial sarcoma of the neck associated with previous head and neck radiation therapy. Synovial sarcoma is a rare neoplasm that uncommonly arises in the neck. Fourteen years after facial and neck radiation therapy for acne, synovial sarcoma of the neck developed in a young man. Possible radiation-induced benign and malignant neoplasms that arise in the head and neck region, either of thyroid or extrathyroid origin, remain a continuing medical problem."}
{"id": "PMID:209776", "title": "Macrophages and resistance to tumours: influence of agents affecting macrophages and delayed-type hypersensitivity on resistance to tumours inducing concomitant immunity.", "content": "Early, specific concomitant immunity to each of four tumours was inhibited by treatment with silica or carrageenan. Late, non-specific concomitant immunity was, with one exception, not inhibited by these agents. Treatment of non-immune mice with silica at certain critical periods before challenge promoted the growth of four of six syngeneic methylcholanthrene-induced tumours in their feet. Treatment with carrageenan was much less effective. Early and late concomitant immunity were inhibited by one or more agents inhibiting delayed-type hypersensitivity: irradiation, niridazole and reserpine. Irradiation of non-immune mice did not effect the growth of tumours in their feet. Treatment of non-immune mice with niridazole or reserpine actually inhibited the growth of some tumours. It is suggested that (a) mice offer some natural resistance to tumour growth, macrophages perhaps being effectors; (b) some tumour isografts may survive only if an inflammatory reaction occurs; (c) mechanisms akin to those of delayed-type hypersensitivity operate in the expression of concomitant immunity; (d) macrophages are important in early, specific concomitant immunity, but perhaps less so in the late non-specific phase.", "contents": "Macrophages and resistance to tumours: influence of agents affecting macrophages and delayed-type hypersensitivity on resistance to tumours inducing concomitant immunity. Early, specific concomitant immunity to each of four tumours was inhibited by treatment with silica or carrageenan. Late, non-specific concomitant immunity was, with one exception, not inhibited by these agents. Treatment of non-immune mice with silica at certain critical periods before challenge promoted the growth of four of six syngeneic methylcholanthrene-induced tumours in their feet. Treatment with carrageenan was much less effective. Early and late concomitant immunity were inhibited by one or more agents inhibiting delayed-type hypersensitivity: irradiation, niridazole and reserpine. Irradiation of non-immune mice did not effect the growth of tumours in their feet. Treatment of non-immune mice with niridazole or reserpine actually inhibited the growth of some tumours. It is suggested that (a) mice offer some natural resistance to tumour growth, macrophages perhaps being effectors; (b) some tumour isografts may survive only if an inflammatory reaction occurs; (c) mechanisms akin to those of delayed-type hypersensitivity operate in the expression of concomitant immunity; (d) macrophages are important in early, specific concomitant immunity, but perhaps less so in the late non-specific phase."}
{"id": "PMID:209777", "title": "A testosterone-secreting adrenal cortical adenoma.", "content": "A virilizing, gonadotrophin-responsive adrenal cortical adenoma was removed from a 54-year-old woman. Following removal of the tumour, which contained and secreted androgens and estradiol, serum gonadotrophins rose to menopausal levels and the patient experienced menopausal symptoms. Pre-operative attempts to localize the source of androgens were unsuccessful.", "contents": "A testosterone-secreting adrenal cortical adenoma. A virilizing, gonadotrophin-responsive adrenal cortical adenoma was removed from a 54-year-old woman. Following removal of the tumour, which contained and secreted androgens and estradiol, serum gonadotrophins rose to menopausal levels and the patient experienced menopausal symptoms. Pre-operative attempts to localize the source of androgens were unsuccessful."}
{"id": "PMID:209778", "title": "Pathogenesis of fowlpox in laying hens.", "content": "Egg production dropped after hens were inoculated with fowlpox virus originally isolated from a natural mild infection. The drop started from the 2nd week and continued to the 5th week after inoculation. All birds developed focal lesions at the site of inoculation, and some developed secondary lesions. The drop in individual birds was related to the severity of lesions. Birds challenged with fowlpox virus fifteen months after vaccination with pigeon pox vaccine were susceptible.", "contents": "Pathogenesis of fowlpox in laying hens. Egg production dropped after hens were inoculated with fowlpox virus originally isolated from a natural mild infection. The drop started from the 2nd week and continued to the 5th week after inoculation. All birds developed focal lesions at the site of inoculation, and some developed secondary lesions. The drop in individual birds was related to the severity of lesions. Birds challenged with fowlpox virus fifteen months after vaccination with pigeon pox vaccine were susceptible."}
{"id": "PMID:209779", "title": "Poxvirus infection in a spectacled Amazon parrot (Amazona albifrons).", "content": "Avian pox was determined to be the cause of death of a spectacled Amazon parrot (Amazona albifrons). Intracytoplasmic inclusion bodies were visualized by light microscopy in esophageal and bronchial epithelial lesions. Electron microscopy revealed pox-virus virions in the inclusions.", "contents": "Poxvirus infection in a spectacled Amazon parrot (Amazona albifrons). Avian pox was determined to be the cause of death of a spectacled Amazon parrot (Amazona albifrons). Intracytoplasmic inclusion bodies were visualized by light microscopy in esophageal and bronchial epithelial lesions. Electron microscopy revealed pox-virus virions in the inclusions."}
{"id": "PMID:209782", "title": "Reexpression of HPRT activity following cell fusion with polyethylene glycol.", "content": "Polyethylene glycol-1000 (PEG-1000) induced fusion of HPRT (E.C. 2.4.2.8) deficient Chinese hamster cells with alpha-galactosidase A (E.C. 2.3.1.22) deficient cells from a patient with Fabry's disease yielded hybrids which contained both human and hamster HPRT, G6PD (E.C. 1.1.1.49), and APRT (E.C. 2.4.2.7) and Chinese hamster alpha-galactosidase B. Thus PEG-1000 mediated somatic cell fusion led to reexpression of Chinese hamster HPRT. It did not restore the expression of human alpha-galactosidase. Since PEG-1000 treatment of HPRT- Chinese hamster cells in the absence of human cells yielded no HPRT+ cells, it is concluded that the element responsible for the restoration of rodent HPRT was contributed by the human cells and not by the agent employed to promote fusion.", "contents": "Reexpression of HPRT activity following cell fusion with polyethylene glycol. Polyethylene glycol-1000 (PEG-1000) induced fusion of HPRT (E.C. 2.4.2.8) deficient Chinese hamster cells with alpha-galactosidase A (E.C. 2.3.1.22) deficient cells from a patient with Fabry's disease yielded hybrids which contained both human and hamster HPRT, G6PD (E.C. 1.1.1.49), and APRT (E.C. 2.4.2.7) and Chinese hamster alpha-galactosidase B. Thus PEG-1000 mediated somatic cell fusion led to reexpression of Chinese hamster HPRT. It did not restore the expression of human alpha-galactosidase. Since PEG-1000 treatment of HPRT- Chinese hamster cells in the absence of human cells yielded no HPRT+ cells, it is concluded that the element responsible for the restoration of rodent HPRT was contributed by the human cells and not by the agent employed to promote fusion."}
{"id": "PMID:209780", "title": "Demyelinating peripheral neuropathy in a guinea hen associated with subacute lead intoxication.", "content": "In mammalian species lead acts primarily as a neurotoxin. Lead poisoning is common in avian species but lesions in the nervous system have not been associated with it. This paper describes a peripheral neuropathy with fragmentation and segmental demyelination of fibers in the sciatic nerves of an adult guinea hen (Numida meleagris) which died of lead poisoning.", "contents": "Demyelinating peripheral neuropathy in a guinea hen associated with subacute lead intoxication. In mammalian species lead acts primarily as a neurotoxin. Lead poisoning is common in avian species but lesions in the nervous system have not been associated with it. This paper describes a peripheral neuropathy with fragmentation and segmental demyelination of fibers in the sciatic nerves of an adult guinea hen (Numida meleagris) which died of lead poisoning."}
{"id": "PMID:209781", "title": "Effect of avian adeno-associated virus on pathogenicity of Tipton virus in chicks.", "content": "The avian adeno-associated virus (A-AV) reduced the pathogenicity of an adenovirus infection in vivo. Groups of chicks were infected with Tipton virus alone or in combination with high or low doses of A-AV. In both trials, the associated virus delayed and reduced chick mortality. This effect was dose-dependent and significant at the higher dose level.", "contents": "Effect of avian adeno-associated virus on pathogenicity of Tipton virus in chicks. The avian adeno-associated virus (A-AV) reduced the pathogenicity of an adenovirus infection in vivo. Groups of chicks were infected with Tipton virus alone or in combination with high or low doses of A-AV. In both trials, the associated virus delayed and reduced chick mortality. This effect was dose-dependent and significant at the higher dose level."}
{"id": "PMID:209795", "title": "Cigarette smoking and HDL cholesterol: the Framingham offspring study.", "content": "High density lipoproteins were measured on fasting blood samples from 4107 men and women. Control for reported alcohol consumption and subscapular skinfold thickness using multiple regression analysis allowed an examination of the relationship between cigarette smoking and HDL cholesterol. Cigarette smoking was found to be associated with an average difference in HDL cholesterol of about 4 mg/dl in men and 6 mg/dl in women. Furthermore, when heavy alcohol drinkers were eliminated a significant negative association between number of cigarettes smoked and HDL cholesterol was demonstrable in both men and women. There was no evidence that former cigarette smokers, with the exception of those who switched to cigars or pipes or had quit less than one year, had lower HDL levels. Cigar or pipe smokers who had never smoked cigarettes had alcohol- and skinfold-adjusted HDL cholesterol comparable to the non-smoker. These observations indicate another possible link between inhaled tobacco smoke and the atherosclerotic process and suggest the need for further studies and experiments that might clarify the mutual relationship of HDL cholesterol, cigarette smoking and the atherosclerotic process.", "contents": "Cigarette smoking and HDL cholesterol: the Framingham offspring study. High density lipoproteins were measured on fasting blood samples from 4107 men and women. Control for reported alcohol consumption and subscapular skinfold thickness using multiple regression analysis allowed an examination of the relationship between cigarette smoking and HDL cholesterol. Cigarette smoking was found to be associated with an average difference in HDL cholesterol of about 4 mg/dl in men and 6 mg/dl in women. Furthermore, when heavy alcohol drinkers were eliminated a significant negative association between number of cigarettes smoked and HDL cholesterol was demonstrable in both men and women. There was no evidence that former cigarette smokers, with the exception of those who switched to cigars or pipes or had quit less than one year, had lower HDL levels. Cigar or pipe smokers who had never smoked cigarettes had alcohol- and skinfold-adjusted HDL cholesterol comparable to the non-smoker. These observations indicate another possible link between inhaled tobacco smoke and the atherosclerotic process and suggest the need for further studies and experiments that might clarify the mutual relationship of HDL cholesterol, cigarette smoking and the atherosclerotic process."}
{"id": "PMID:209796", "title": "Pharmacological profile of BR-931, a new hypolipidemic agent that increases high-density lipoproteins.", "content": "BR-931 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl)-acetamide], a new hypolipidemic agent of low toxicity, was evaluated in several tests of lipolysis and hyperlipidemia in rats, and in the cholesterol-induced atherosclerosis in rabbits. Significant hypolipidemic activity was observed in rats with doses of the agent at 12.5--50 mg/kg. In the Triton-induced hyperlipidemia, 50 mg BR-931 per kg was equieffective as 200 mg of clofibrate (CPIB) per kg. In contrast with CPIB, BR-931 exerted a powerful antilipolytic activity against epinephrine, ACTH, nicotine and cold exposure. BR-931 was particularly effective in diet-induced hyperlipidemias. Ethanol lipemia was totally prevented by the agent at 100 mg/kg. With Nath's diet, doses as low as 25 mg/kg significantly reduced hypercholesterolemia and hypertriglyceridemia. In these last two tests, the distribution of lipoprotein cholesterol was also determined. CPIB did not affect HDL cholesterol levels that had been decreased by the diets; in contrast, BR-931, already at doses of 50 mg/kg, brought the HDL/total cholesterol ratio back toward normal. A significant HDL cholesterol increase, together with some reduction of atheromatosis, was also observed in cholesterol-fed rabbits. BR-931,  a potent inducer of liver peroxisones and of mitochondrial carmitine acetyltransferase, appears to be a hypolipidemic agent of high efficacy and low toxicity for the clinical treatment of hyperlipidemias and atherosclerosis.", "contents": "Pharmacological profile of BR-931, a new hypolipidemic agent that increases high-density lipoproteins. BR-931 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl)-acetamide], a new hypolipidemic agent of low toxicity, was evaluated in several tests of lipolysis and hyperlipidemia in rats, and in the cholesterol-induced atherosclerosis in rabbits. Significant hypolipidemic activity was observed in rats with doses of the agent at 12.5--50 mg/kg. In the Triton-induced hyperlipidemia, 50 mg BR-931 per kg was equieffective as 200 mg of clofibrate (CPIB) per kg. In contrast with CPIB, BR-931 exerted a powerful antilipolytic activity against epinephrine, ACTH, nicotine and cold exposure. BR-931 was particularly effective in diet-induced hyperlipidemias. Ethanol lipemia was totally prevented by the agent at 100 mg/kg. With Nath's diet, doses as low as 25 mg/kg significantly reduced hypercholesterolemia and hypertriglyceridemia. In these last two tests, the distribution of lipoprotein cholesterol was also determined. CPIB did not affect HDL cholesterol levels that had been decreased by the diets; in contrast, BR-931, already at doses of 50 mg/kg, brought the HDL/total cholesterol ratio back toward normal. A significant HDL cholesterol increase, together with some reduction of atheromatosis, was also observed in cholesterol-fed rabbits. BR-931,  a potent inducer of liver peroxisones and of mitochondrial carmitine acetyltransferase, appears to be a hypolipidemic agent of high efficacy and low toxicity for the clinical treatment of hyperlipidemias and atherosclerosis."}
{"id": "PMID:209797", "title": "Studies on the metabolism of the lipoprotein Lp (a) in man.", "content": "Lp(a) was isolated and labeled by reductive alkylation. Radioactivity only entered the protein moiety of the lipoprotein. No change in the immunological or physicochemical properties of Lp(a) was noted after the radiomethylation. After incubation of labeled Lp(a) with whole serum for 24 h in vitro, more than 99% of the radioactivity of the incubated sample was found in Lp(a). In 4 subjects Lp(a) was injected intravenously. A linear decline of the specific activity of Lp(a) in the serum was found when it was plotted semilogarithmically against time. Half-lives of Lp(a) in the serum were 35, 38, 53 and 58 h. In one subject, the \"soluble\" and the \"insoluble\" apoproteins of Lp(a) showed the same half-life as the whole Lp(a) molecule. This suggests that no exchange of Lp(a) apoproteins with lipoproteins of other density classes took place. At different times after the injection of Lp(a), 3--8% of the radioactivity of the serum was found in Lp B, and less than 2% of the radioactivity was detectable in VLDL and the fraction having a density of greater than 1.110 g/ml.", "contents": "Studies on the metabolism of the lipoprotein Lp (a) in man. Lp(a) was isolated and labeled by reductive alkylation. Radioactivity only entered the protein moiety of the lipoprotein. No change in the immunological or physicochemical properties of Lp(a) was noted after the radiomethylation. After incubation of labeled Lp(a) with whole serum for 24 h in vitro, more than 99% of the radioactivity of the incubated sample was found in Lp(a). In 4 subjects Lp(a) was injected intravenously. A linear decline of the specific activity of Lp(a) in the serum was found when it was plotted semilogarithmically against time. Half-lives of Lp(a) in the serum were 35, 38, 53 and 58 h. In one subject, the \"soluble\" and the \"insoluble\" apoproteins of Lp(a) showed the same half-life as the whole Lp(a) molecule. This suggests that no exchange of Lp(a) apoproteins with lipoproteins of other density classes took place. At different times after the injection of Lp(a), 3--8% of the radioactivity of the serum was found in Lp B, and less than 2% of the radioactivity was detectable in VLDL and the fraction having a density of greater than 1.110 g/ml."}
{"id": "PMID:209798", "title": "Acute effect of dietary therapy of type IV hyperlipoproteinaemia on the serum and lipoprotein concentrations and relative composition.", "content": "In a detailed study the acute effect of diet and hospital admission on the plasma and lipoprotein lipid concentrations and composition was studied in 28 patients with type IV hyperlipoproteinaemia. Within 6 days there were significant falls in the mean serum cholesterol and triglycerides, very low density lipoprotein (VLDL) cholesterol and triglycerides and in high density lipoprotein triglycerides. These changes were accompanied by a significant rise in the mean low density lipoprotein (LDL) cholesterol concentrations. Using multiple regession models highly significant predictions of the change in VLDL triglyceride (R2 = 0.71) and LDL cholesterol (R2 = 0.47) were obtained utilising the pre-treatment lipoprotein levels as independant variables. Since elevated LDL cholesterol concentations are associated with atherosclerotic disease such models may have important therapeutic applications.", "contents": "Acute effect of dietary therapy of type IV hyperlipoproteinaemia on the serum and lipoprotein concentrations and relative composition. In a detailed study the acute effect of diet and hospital admission on the plasma and lipoprotein lipid concentrations and composition was studied in 28 patients with type IV hyperlipoproteinaemia. Within 6 days there were significant falls in the mean serum cholesterol and triglycerides, very low density lipoprotein (VLDL) cholesterol and triglycerides and in high density lipoprotein triglycerides. These changes were accompanied by a significant rise in the mean low density lipoprotein (LDL) cholesterol concentrations. Using multiple regession models highly significant predictions of the change in VLDL triglyceride (R2 = 0.71) and LDL cholesterol (R2 = 0.47) were obtained utilising the pre-treatment lipoprotein levels as independant variables. Since elevated LDL cholesterol concentations are associated with atherosclerotic disease such models may have important therapeutic applications."}
{"id": "PMID:209799", "title": "Lipoprotein composition in diabetes mellitus.", "content": "Lipoprotein cholesterol and triglyceride levels have been determined in normal and diabetic Pima Indian women aged 20-35, HDL cholesterol levels were lower, LDL cholesterol levels were higher, and the ratio of HDL cholesterol/LDL cholesterol, a reflection of lipoprotein cholesterol distribution, was lower in the diabetics compared to the normals. VLDL triglyceride levels were also elevated in the diabetics. An analysis of lipoprotein composition suggested that these changes primarily reflect changes in numbers of particles, since lipid composition and lipid/protein ratios were similar in lipoproteins isolated from normals and diabetics. The ratio of ester/free cholesterol in LDL and HDL was lower in normal Pima Indians than in a comparable group of Caucasians, although plasma LCAT activity was not significantly different. The data indicate that diabetes may be associated with shifts in distribution of LDL and HDL, as well as with increases in VLDL.", "contents": "Lipoprotein composition in diabetes mellitus. Lipoprotein cholesterol and triglyceride levels have been determined in normal and diabetic Pima Indian women aged 20-35, HDL cholesterol levels were lower, LDL cholesterol levels were higher, and the ratio of HDL cholesterol/LDL cholesterol, a reflection of lipoprotein cholesterol distribution, was lower in the diabetics compared to the normals. VLDL triglyceride levels were also elevated in the diabetics. An analysis of lipoprotein composition suggested that these changes primarily reflect changes in numbers of particles, since lipid composition and lipid/protein ratios were similar in lipoproteins isolated from normals and diabetics. The ratio of ester/free cholesterol in LDL and HDL was lower in normal Pima Indians than in a comparable group of Caucasians, although plasma LCAT activity was not significantly different. The data indicate that diabetes may be associated with shifts in distribution of LDL and HDL, as well as with increases in VLDL."}
{"id": "PMID:209800", "title": "Serum lipoprotein abnormalities in renal allograft recipients.", "content": "Detailed lipid composition of serum and isolated lipoprotein fractions in male and female transplant recipients has been determined. Results have been compared with appropriate controls and a number of abnormalities have become apparent: (i) Serum total cholesterol, triglyceride and phospholipid levels were significantly elevated in transplant recipients. (ii) All lipid classes VLDL were significantly increased in both male and female patients. (iii) LDL-total cholesterol, triglyceride and phospholipid were significantly raised in female transplant patients, but this was true only for LDL-triglyceride in male patients. (iv) In female patients, HDL-total cholesterol and -triglyceride were significantly elevated, while in male patients, HDL-total cholesterol, but not HDL-triglyceride, was significantly greater than in controls. (v) The ratio of esterified to free cholesterol was significantly reduced in HDL of female transplant recipients. Results from correlation analysis suggest a relationship between some of the lipid abnormalities and renal function in female patients, while in male patients only immunosuppressive therapy is implicated.", "contents": "Serum lipoprotein abnormalities in renal allograft recipients. Detailed lipid composition of serum and isolated lipoprotein fractions in male and female transplant recipients has been determined. Results have been compared with appropriate controls and a number of abnormalities have become apparent: (i) Serum total cholesterol, triglyceride and phospholipid levels were significantly elevated in transplant recipients. (ii) All lipid classes VLDL were significantly increased in both male and female patients. (iii) LDL-total cholesterol, triglyceride and phospholipid were significantly raised in female transplant patients, but this was true only for LDL-triglyceride in male patients. (iv) In female patients, HDL-total cholesterol and -triglyceride were significantly elevated, while in male patients, HDL-total cholesterol, but not HDL-triglyceride, was significantly greater than in controls. (v) The ratio of esterified to free cholesterol was significantly reduced in HDL of female transplant recipients. Results from correlation analysis suggest a relationship between some of the lipid abnormalities and renal function in female patients, while in male patients only immunosuppressive therapy is implicated."}
{"id": "PMID:209802", "title": "Study of cultured skin fibroblasts from patients with and without ischemic heart disease. Metabolism of low density lipoprotein and cholesterol ester, synthesis of cellular lipids and effect of chloroquine on accumulation of cholesterol ester.", "content": "The aim of the present study was to determine whether skin fibroblasts derived from patients with ischemic heart disease (IHD), which could not be related to accepted risk factors, would show a metabolic abnormality with respect to lipid or lipoprotein metabolism. Male patients 30-52 years old suffering from IHD were subdivided into two groups: those in whom IHD was not associated with risk factors such as hypertension, hyperlipoproteinemia, diabetes or smoking (group I); and those in whom heavy smoking was the only major risk factor recognized (group II). The controls were patients with angiographically normal coronary arteries (group III). Skin fibroblasts obtained from these patients were cultured and investigated with respect to metabolism of low density lipoprotein (LDL), synthesis of cellular lipids and induction of cholesterol ester accumulation in the presence of chloroquine, an inhibitor of lysosomal hydrolases. After 24 h incubation, the uptake and degradation of LDL protein in cells from patients of group II was significantly higher than in the controls, group III, but not different from those of group I. Hydrolysis of [3H] cholesterol linoleate, and incorporation of [3H] oleic acid into total lipids and into cholesterol esters was similar in cell cultures of the 3 groups studied. After exposure to chloroquine and LDL, the cells from the different donors accumulated cholesterol ester to a similar extent. Thus, whereas no significant difference was encountered in the lipid and lipoprotein metabolism in cells of patients with IHD without risk factors and controls, some increase in LDL metabolism was seen in cells from patients with IHD and with a history of smoking. It remains to be determined whether this increase was causally related to smoking.", "contents": "Study of cultured skin fibroblasts from patients with and without ischemic heart disease. Metabolism of low density lipoprotein and cholesterol ester, synthesis of cellular lipids and effect of chloroquine on accumulation of cholesterol ester. The aim of the present study was to determine whether skin fibroblasts derived from patients with ischemic heart disease (IHD), which could not be related to accepted risk factors, would show a metabolic abnormality with respect to lipid or lipoprotein metabolism. Male patients 30-52 years old suffering from IHD were subdivided into two groups: those in whom IHD was not associated with risk factors such as hypertension, hyperlipoproteinemia, diabetes or smoking (group I); and those in whom heavy smoking was the only major risk factor recognized (group II). The controls were patients with angiographically normal coronary arteries (group III). Skin fibroblasts obtained from these patients were cultured and investigated with respect to metabolism of low density lipoprotein (LDL), synthesis of cellular lipids and induction of cholesterol ester accumulation in the presence of chloroquine, an inhibitor of lysosomal hydrolases. After 24 h incubation, the uptake and degradation of LDL protein in cells from patients of group II was significantly higher than in the controls, group III, but not different from those of group I. Hydrolysis of [3H] cholesterol linoleate, and incorporation of [3H] oleic acid into total lipids and into cholesterol esters was similar in cell cultures of the 3 groups studied. After exposure to chloroquine and LDL, the cells from the different donors accumulated cholesterol ester to a similar extent. Thus, whereas no significant difference was encountered in the lipid and lipoprotein metabolism in cells of patients with IHD without risk factors and controls, some increase in LDL metabolism was seen in cells from patients with IHD and with a history of smoking. It remains to be determined whether this increase was causally related to smoking."}
{"id": "PMID:209803", "title": "Dyslipoproteinemia in patients with ischemic cerebro-vascular disease: a study of stroke before the age of 55.", "content": "Serum lipoproteins were determined 8-12 weeks after the onset of ischemic cerebro-vascular disease (ICD) in 61 patients, 38 males and 23 females, before the age of 55. The results were compared with those of a matched control material. The diagnosis was based on clinical findings, CSF spectrophotometry, computer tomography, and angiography. Hyperlipoproteinemia was no common finding in these young and middle-aged patients with ICD. The normal mean total serum cholesterol concentration was the result of a slight increase in VLDL cholesterol and a concomitant HDL cholesterol reduction. In men, the HDL cholesterol concentration was lower than expected for any VLDL-TG concentration. The mean value of the HDL cholesterol concentration in the patients was 18% lower than in the control group. On agarose electrophoresis the lipoprotein variants \"late prebeta\", \"sinking prebeta\" and \"rapid beta\" lipoproteins could be demonstrated in the same frequency as in controls. There was no significant correlation between the degree of atherosclerosis, estimated by angiography, and any serum lipoprotein fraction. Several recent studies have stressed the importance of a low HDL concentration as an independent risk factor for atherosclerosis. The decreased HDL cholesterol levels found in the present material require further attention to the possible beneficial role of HDL in ICD.", "contents": "Dyslipoproteinemia in patients with ischemic cerebro-vascular disease: a study of stroke before the age of 55. Serum lipoproteins were determined 8-12 weeks after the onset of ischemic cerebro-vascular disease (ICD) in 61 patients, 38 males and 23 females, before the age of 55. The results were compared with those of a matched control material. The diagnosis was based on clinical findings, CSF spectrophotometry, computer tomography, and angiography. Hyperlipoproteinemia was no common finding in these young and middle-aged patients with ICD. The normal mean total serum cholesterol concentration was the result of a slight increase in VLDL cholesterol and a concomitant HDL cholesterol reduction. In men, the HDL cholesterol concentration was lower than expected for any VLDL-TG concentration. The mean value of the HDL cholesterol concentration in the patients was 18% lower than in the control group. On agarose electrophoresis the lipoprotein variants \"late prebeta\", \"sinking prebeta\" and \"rapid beta\" lipoproteins could be demonstrated in the same frequency as in controls. There was no significant correlation between the degree of atherosclerosis, estimated by angiography, and any serum lipoprotein fraction. Several recent studies have stressed the importance of a low HDL concentration as an independent risk factor for atherosclerosis. The decreased HDL cholesterol levels found in the present material require further attention to the possible beneficial role of HDL in ICD."}
{"id": "PMID:209804", "title": "Experimental hyper-beta-lipoproteinemia and its amelioration by a novel hypolipidemic agent.", "content": "Experimental models for hyper-beta-lipoproteinemia were established in rats and the effects of certain hypolipidemic drugs were studied with these models. In the hyperlipemia induced in rats by feeding a high cholesterol diet, Y-9738 [ethyl 2(4-chlorophenyl)-5-ethoxy-4-oxazoleacetate] produced a dose-dependent reduction of serum cholesterol: such hypolipidemic activity was estimated to be about 7 times as great as that of clofibrate. On the other hand, clofibrate induced hepatomegaly at 100 mg/kg, whereas Y-9738 did not at this dosage, which is about 10 times the effective dose. Hyperlipemia induced by high cholesterol and thiouracil was characterized by increased beta-lipoprotein (heparin-calcium and disc electrophoresis). In this model, Y-9738 showed a dose-dependent lowering effect on beta-lipoprotein cholesterol with a marked decrease in the beta/alpha lipoprotein ratio. A tendency was noted for alpha-lipoprotein to be increased. In contrast, clofibrate exerted no effect on this hyper-beta-lipoproteinemia. These results suggest that the above models may be of value in exploring hyper-beta-lipoproteinemia and that Y-9738 may be more useful than clofibrate in the therapy of hyperlipemia.", "contents": "Experimental hyper-beta-lipoproteinemia and its amelioration by a novel hypolipidemic agent. Experimental models for hyper-beta-lipoproteinemia were established in rats and the effects of certain hypolipidemic drugs were studied with these models. In the hyperlipemia induced in rats by feeding a high cholesterol diet, Y-9738 [ethyl 2(4-chlorophenyl)-5-ethoxy-4-oxazoleacetate] produced a dose-dependent reduction of serum cholesterol: such hypolipidemic activity was estimated to be about 7 times as great as that of clofibrate. On the other hand, clofibrate induced hepatomegaly at 100 mg/kg, whereas Y-9738 did not at this dosage, which is about 10 times the effective dose. Hyperlipemia induced by high cholesterol and thiouracil was characterized by increased beta-lipoprotein (heparin-calcium and disc electrophoresis). In this model, Y-9738 showed a dose-dependent lowering effect on beta-lipoprotein cholesterol with a marked decrease in the beta/alpha lipoprotein ratio. A tendency was noted for alpha-lipoprotein to be increased. In contrast, clofibrate exerted no effect on this hyper-beta-lipoproteinemia. These results suggest that the above models may be of value in exploring hyper-beta-lipoproteinemia and that Y-9738 may be more useful than clofibrate in the therapy of hyperlipemia."}
{"id": "PMID:209806", "title": "Response kinetics of host and experimental solid tumour after adriamycin.", "content": "The effects of adriamycin (Adr) on the solid-tumour model, hepatoma 3924A, and on critical organs of the host, were determined at intervals after single injections of 60 mg/m2 of the agent. A reduced rate of tumour growth was evident 4 days after treatment, continued to Day 11, and then returned to rates comparable to control values. On Day 11 tumour volumes of treated animals were 38% of control. During the period of reduced growth, 3H-TdR incorporation into tumour DNA and percentage labelled tumour cells were less than control values. DNA concentration in tumour was not affected by drug treatment, which differs from observations made in other studies employing 5-fluorouracil (FU). No evidence of significantly increased necrosis or fibrosis of the tumour was found after Adr. The Adr treatment caused loss of 60% of the tibial marrow by Day 4, as measured by total DNA content. Marrow DNA recovered to control levels between Days 7 and 11. Incorporation of 3H-TdR into heart DNA was reduced more than 40% during the first week after Adr treatment; enhanced incorporation was observed on Day 11, and control levels were attained by Day 17. No significant pathological evidence of cardiac toxicity was found 2-21 days after Adr but degeneration of myocardial cells and oedema was prominent at 14 weeks.", "contents": "Response kinetics of host and experimental solid tumour after adriamycin. The effects of adriamycin (Adr) on the solid-tumour model, hepatoma 3924A, and on critical organs of the host, were determined at intervals after single injections of 60 mg/m2 of the agent. A reduced rate of tumour growth was evident 4 days after treatment, continued to Day 11, and then returned to rates comparable to control values. On Day 11 tumour volumes of treated animals were 38% of control. During the period of reduced growth, 3H-TdR incorporation into tumour DNA and percentage labelled tumour cells were less than control values. DNA concentration in tumour was not affected by drug treatment, which differs from observations made in other studies employing 5-fluorouracil (FU). No evidence of significantly increased necrosis or fibrosis of the tumour was found after Adr. The Adr treatment caused loss of 60% of the tibial marrow by Day 4, as measured by total DNA content. Marrow DNA recovered to control levels between Days 7 and 11. Incorporation of 3H-TdR into heart DNA was reduced more than 40% during the first week after Adr treatment; enhanced incorporation was observed on Day 11, and control levels were attained by Day 17. No significant pathological evidence of cardiac toxicity was found 2-21 days after Adr but degeneration of myocardial cells and oedema was prominent at 14 weeks."}
{"id": "PMID:209807", "title": "Effects of sensitizers on cell respiration: 1. Factors influencing the effects of hypoxic cell radiosensitizers on oxygen utilization of tumour and cultured mammalian cells.", "content": "We have investigated the effects of 24 nitrocompounds, differing in their half-reduction potential, on the respiration in vitro of Ehrlich ascites tumour cells and cultured V79 lung cells. Many drugs with redox potentials more positive than--0.35 stimulated oxygen utilization in the presence of glucose. Glucose had little effect on the inhibition of respiration by drugs with oxidation-reduction potentials more negative than--0.38. Nitrocompounds that inhibited Ehrilch cell respiration in the presence of glucose, also inhibited intracellular reduction of ferricytochrome (c+c1). Drugs that stimulated oxygen utilization also stimuated intracellular (c \" c1). Drugs that stimulated oxygen utilization also stimulated intracellular reduction of ferricytochrome (c + c1). A correlation between drug oxidation-reduction potential and stimulation of oxygen utilization in KCN-inhibited cells was found.", "contents": "Effects of sensitizers on cell respiration: 1. Factors influencing the effects of hypoxic cell radiosensitizers on oxygen utilization of tumour and cultured mammalian cells. We have investigated the effects of 24 nitrocompounds, differing in their half-reduction potential, on the respiration in vitro of Ehrlich ascites tumour cells and cultured V79 lung cells. Many drugs with redox potentials more positive than--0.35 stimulated oxygen utilization in the presence of glucose. Glucose had little effect on the inhibition of respiration by drugs with oxidation-reduction potentials more negative than--0.38. Nitrocompounds that inhibited Ehrilch cell respiration in the presence of glucose, also inhibited intracellular reduction of ferricytochrome (c+c1). Drugs that stimulated oxygen utilization also stimuated intracellular (c \" c1). Drugs that stimulated oxygen utilization also stimulated intracellular reduction of ferricytochrome (c + c1). A correlation between drug oxidation-reduction potential and stimulation of oxygen utilization in KCN-inhibited cells was found."}
{"id": "PMID:209808", "title": "The neurotoxicity of misonidazole and its relationship to dose, half-life and concentration in the serum.", "content": "Misonidazole has been given to a total of 87 patients. Neurotoxicity has occurred--convulsions with the higher doses and peripheral neuropathy with the lowern ones. The data from 34 patients receiving 4--7 doses has been analysed. Peripheral neuropathy is related to the total tissue exposure. By monitoring serum levels and controlling the total dose given, convulsions are avoidable and peripheral neuropathy restricted to a low and acceptable level.", "contents": "The neurotoxicity of misonidazole and its relationship to dose, half-life and concentration in the serum. Misonidazole has been given to a total of 87 patients. Neurotoxicity has occurred--convulsions with the higher doses and peripheral neuropathy with the lowern ones. The data from 34 patients receiving 4--7 doses has been analysed. Peripheral neuropathy is related to the total tissue exposure. By monitoring serum levels and controlling the total dose given, convulsions are avoidable and peripheral neuropathy restricted to a low and acceptable level."}
{"id": "PMID:209805", "title": "[Acute intestinal amebiasis treated with aminosidine].", "content": "A clinical-therapeutic assay carried out at the \"William Soler\" pediatric teaching hospital in children admitted due to an acute diarrheic syndrome and treated with aminosidine sulfate is presented. Histolytic ameba is still an element to be considered in the origin of gastroenteritis. The therapeutic action of aminosidine is evaluated.", "contents": "[Acute intestinal amebiasis treated with aminosidine]. A clinical-therapeutic assay carried out at the \"William Soler\" pediatric teaching hospital in children admitted due to an acute diarrheic syndrome and treated with aminosidine sulfate is presented. Histolytic ameba is still an element to be considered in the origin of gastroenteritis. The therapeutic action of aminosidine is evaluated."}
{"id": "PMID:209809", "title": "Peripheral neuropathy related to misonidazole: incidence and pathology.", "content": "The human tolerance to multiple dosages of misonidazole (Ro-07-0582) was studied in 28 patients with different types of malignant neoplasias. The mean total dose for this group of patients was 16.2 g. The main toxicity was peripheral neuropathy with an overall incidence of 35%. This neuropathy occurred more frequently and with greater severity when the drug was administered 3 times a week and when patients received total doses of over 18 g. The best tolerated schedule appears to be once or twice a week up to total dosages of 18 g or less (approximately 11 g/m2). Electron microscopy of a sural nerve biopsy from an affected patient revealed residual of previous distal axonal degeneration, with some segmental demyelination and remyelination, which affected both large and small myelinated nerve fibres.", "contents": "Peripheral neuropathy related to misonidazole: incidence and pathology. The human tolerance to multiple dosages of misonidazole (Ro-07-0582) was studied in 28 patients with different types of malignant neoplasias. The mean total dose for this group of patients was 16.2 g. The main toxicity was peripheral neuropathy with an overall incidence of 35%. This neuropathy occurred more frequently and with greater severity when the drug was administered 3 times a week and when patients received total doses of over 18 g. The best tolerated schedule appears to be once or twice a week up to total dosages of 18 g or less (approximately 11 g/m2). Electron microscopy of a sural nerve biopsy from an affected patient revealed residual of previous distal axonal degeneration, with some segmental demyelination and remyelination, which affected both large and small myelinated nerve fibres."}
{"id": "PMID:209810", "title": "Further clinical experiences of a phase I study with the hypoxic cell radiosensitizer misonidazole.", "content": "Since April 1976 we have performed clinical investigations with multiple doses of the hypoxic cell radiosensitizer misonidazole in 21 patients. A significant side effect of the drug was the development of peripheral sensory neuropathies in 13 patients (8 mild, 5 severe) and of a transient acute organic psychosyndrome in 2 of the 5 patients with a severe polyneuropathy. The severity of the polyneuropathies is related to the total dose of misonidazole and the overall time of drug administration. Treatment schedules designed to obtain the desired sensitizing effect without neurological side effects are under investigation.", "contents": "Further clinical experiences of a phase I study with the hypoxic cell radiosensitizer misonidazole. Since April 1976 we have performed clinical investigations with multiple doses of the hypoxic cell radiosensitizer misonidazole in 21 patients. A significant side effect of the drug was the development of peripheral sensory neuropathies in 13 patients (8 mild, 5 severe) and of a transient acute organic psychosyndrome in 2 of the 5 patients with a severe polyneuropathy. The severity of the polyneuropathies is related to the total dose of misonidazole and the overall time of drug administration. Treatment schedules designed to obtain the desired sensitizing effect without neurological side effects are under investigation."}
{"id": "PMID:209811", "title": "The optimum regime for the administration of misonidazole and the establishment of multi-centre clinical trials.", "content": "The amount of misonidazole which may be given to one patient is limited because of the risk of neurotoxicity. The drug may be given with every treatment of a multi-fraction course of radiotherapy or only with some of the treatments. The number of radiotherapy treatments can be reduced or multiple treatments given after each dose of the drug. Experience in 19 patients given daily doses of misonidazole is reported. This is practical regime to be considered for clinical trials of this hypoxic cell sensitizer.", "contents": "The optimum regime for the administration of misonidazole and the establishment of multi-centre clinical trials. The amount of misonidazole which may be given to one patient is limited because of the risk of neurotoxicity. The drug may be given with every treatment of a multi-fraction course of radiotherapy or only with some of the treatments. The number of radiotherapy treatments can be reduced or multiple treatments given after each dose of the drug. Experience in 19 patients given daily doses of misonidazole is reported. This is practical regime to be considered for clinical trials of this hypoxic cell sensitizer."}
{"id": "PMID:209812", "title": "Induction of some features of glial differentiation in primary cultures of human gliomas by treatment with dibutyrl cyclic AMP.", "content": "Explants from 18 gliomas were cultured for periods up to 7 weeks and studied by light microscopy scanning and transmission electron microscopy. Well-differentiated tumor tissue gave rise to early outgrowths of stellate cells showing process orientation. Poorly-differentiated tissue produced a more haphazard out-growth of pleomorphic cells with few processes and flattened pseudopodia. Mean circadian cell displacement was several times greater in poorly-differentiated cells, but was significantly and reversibly reduced by treatment and dibutyryl cAMP (5 X 10(-4)M) for 48 h. Reduction in motility was directly correlated with a change in cell morphology to a more stellate form. Well-differentiated cells had a smooth surface with ruffling restricted to the ends of processes and highly orientated glial filament and microfilament bundles. The poorly-differentiated cell surface had a microvillous, blebbed appearance and ruffling regularly occurred around the edge of the cytoplasm. Glial filaments and microfilaments were fewer and less well orientated in the poorly-differentiated cells; sites of adhesion to the substratum were fewer than in well-differentiated cells. Treatment of malignant cultures with dibutyryl cAMP resulted in smoothing of the cell surface, retraction of processes into thin pseudopodia and the appearance of microfilament bundles within the cells. These features marked the apparent cyto-differentiation. However, there was a loss of attachment, disappearance of microtubules and loss of glial filaments in the cytoplasm which was not compatible with differentiation. Intracellular recordings of membrane potentials gave a significantly higher mean value for well-differentiated cells. The mean membrane potential and input resistance of poorly-differentiated cells was unchanged by the addition of dibutyryl cAMP. The results of this study suggest that some, but not all, features of mature glia are restored in malignant tumour cells by cAMP treatment.", "contents": "Induction of some features of glial differentiation in primary cultures of human gliomas by treatment with dibutyrl cyclic AMP. Explants from 18 gliomas were cultured for periods up to 7 weeks and studied by light microscopy scanning and transmission electron microscopy. Well-differentiated tumor tissue gave rise to early outgrowths of stellate cells showing process orientation. Poorly-differentiated tissue produced a more haphazard out-growth of pleomorphic cells with few processes and flattened pseudopodia. Mean circadian cell displacement was several times greater in poorly-differentiated cells, but was significantly and reversibly reduced by treatment and dibutyryl cAMP (5 X 10(-4)M) for 48 h. Reduction in motility was directly correlated with a change in cell morphology to a more stellate form. Well-differentiated cells had a smooth surface with ruffling restricted to the ends of processes and highly orientated glial filament and microfilament bundles. The poorly-differentiated cell surface had a microvillous, blebbed appearance and ruffling regularly occurred around the edge of the cytoplasm. Glial filaments and microfilaments were fewer and less well orientated in the poorly-differentiated cells; sites of adhesion to the substratum were fewer than in well-differentiated cells. Treatment of malignant cultures with dibutyryl cAMP resulted in smoothing of the cell surface, retraction of processes into thin pseudopodia and the appearance of microfilament bundles within the cells. These features marked the apparent cyto-differentiation. However, there was a loss of attachment, disappearance of microtubules and loss of glial filaments in the cytoplasm which was not compatible with differentiation. Intracellular recordings of membrane potentials gave a significantly higher mean value for well-differentiated cells. The mean membrane potential and input resistance of poorly-differentiated cells was unchanged by the addition of dibutyryl cAMP. The results of this study suggest that some, but not all, features of mature glia are restored in malignant tumour cells by cAMP treatment."}
{"id": "PMID:209813", "title": "Collagen prolyl hydroxylase levels in experimental paraquat poisoning.", "content": "Collagen prolyl hydroxylase activity was measured in lung, liver, kidney and serum in rats killed on 7 successive days following a single toxic dose of paraquat. The enzyme activity in liver initially fell, then returned to normal, and no change was found in kidney. In contrast a 5-fold rise was observed in lung enzyme level, reaching of maximum on the 5th day. A parallel rise in serum activity was also found. The onset of these enzyme elevations corresponds to the early histological appearance of cellular proliferation in lung alveoli.", "contents": "Collagen prolyl hydroxylase levels in experimental paraquat poisoning. Collagen prolyl hydroxylase activity was measured in lung, liver, kidney and serum in rats killed on 7 successive days following a single toxic dose of paraquat. The enzyme activity in liver initially fell, then returned to normal, and no change was found in kidney. In contrast a 5-fold rise was observed in lung enzyme level, reaching of maximum on the 5th day. A parallel rise in serum activity was also found. The onset of these enzyme elevations corresponds to the early histological appearance of cellular proliferation in lung alveoli."}
{"id": "PMID:209814", "title": "Primary mucinous carcinoma of the skin.", "content": "Only twenty-seven cases of primary mucinous carcinoma of the skin have been reported. Three additional cases are included in this paper. The clinical presentation is distinctive; they are found most commonly in middle-aged, black males in the head and neck region as painless nodules, usually less than 3 cm in diameter. Previous reports have indicated the probable sweat gland origin of these tumours; one of our cases demonstrates a transition from a solid hidradenoma-like pattern to nests of tumour cells floating in mucin lakes, adding support for the sweat gland hypothesis. The clinical behaviour is relatively benign; late recurrences are common but metastases are rare. Only one case had widespread metastases. Although the histological appearance is distinctive, other primary sites first must be excluded. Local excision is the treatment of choice.", "contents": "Primary mucinous carcinoma of the skin. Only twenty-seven cases of primary mucinous carcinoma of the skin have been reported. Three additional cases are included in this paper. The clinical presentation is distinctive; they are found most commonly in middle-aged, black males in the head and neck region as painless nodules, usually less than 3 cm in diameter. Previous reports have indicated the probable sweat gland origin of these tumours; one of our cases demonstrates a transition from a solid hidradenoma-like pattern to nests of tumour cells floating in mucin lakes, adding support for the sweat gland hypothesis. The clinical behaviour is relatively benign; late recurrences are common but metastases are rare. Only one case had widespread metastases. Although the histological appearance is distinctive, other primary sites first must be excluded. Local excision is the treatment of choice."}
{"id": "PMID:209816", "title": "Translational recognition of the 5'-terminal 7-methylguanosine of globin messenger RNA as a function of ionic strength.", "content": "The translation of rabbit globin mRNA in cell-free systems derived from either wheat germ or rabbit reticulocyte was studied in the presence of various analogues of the methylated 5' terminus (cap) as a function of ionic strength. Inhibition by these analogues was strongly enhanced by increasing concentrations of KCl, K(OAc), Na(OAc), or NH4(OAc). At appropriate concentrations of K(OAc), both cell-free systems were equally sensitive to inhibition by m7GTP. At 50 mM K(OAc), the reticulocyte system was not sensitive to m7GMP or m7GTP, but at higher concentrations up to 200 mM K(OAc), both nucleotides caused strong inhibition. The compound in m7G5'ppp5'Am was inhibitory at all concentrations of K(OAc) ranging from 50 to 200 mM, although more strongly so at the higher concentrations. Over the same range of nucleotide concentrations, the compounds GMP, GTP, and G5'ppp5'Am were not inhibitors. The mobility on sodium dodecyl sulfate-polyacrylamide electrophoresis of the translation product was that of globin at all K(OAc) concentrations in the presence of m7GTP. Globin mRNA from which the terminal m7GTP group had been removed by chemical treatment (periodate-cyclohexylamine-alkaline phosphatase) or enzymatic treatment (tobacco acid pyrophosphatase-alkaline phosphatase)  was translated less efficiently than untreated globin mRNA at higher K(OAc) concentrations, but retained appreciable activity at low K(OAc) concentrations.", "contents": "Translational recognition of the 5'-terminal 7-methylguanosine of globin messenger RNA as a function of ionic strength. The translation of rabbit globin mRNA in cell-free systems derived from either wheat germ or rabbit reticulocyte was studied in the presence of various analogues of the methylated 5' terminus (cap) as a function of ionic strength. Inhibition by these analogues was strongly enhanced by increasing concentrations of KCl, K(OAc), Na(OAc), or NH4(OAc). At appropriate concentrations of K(OAc), both cell-free systems were equally sensitive to inhibition by m7GTP. At 50 mM K(OAc), the reticulocyte system was not sensitive to m7GMP or m7GTP, but at higher concentrations up to 200 mM K(OAc), both nucleotides caused strong inhibition. The compound in m7G5'ppp5'Am was inhibitory at all concentrations of K(OAc) ranging from 50 to 200 mM, although more strongly so at the higher concentrations. Over the same range of nucleotide concentrations, the compounds GMP, GTP, and G5'ppp5'Am were not inhibitors. The mobility on sodium dodecyl sulfate-polyacrylamide electrophoresis of the translation product was that of globin at all K(OAc) concentrations in the presence of m7GTP. Globin mRNA from which the terminal m7GTP group had been removed by chemical treatment (periodate-cyclohexylamine-alkaline phosphatase) or enzymatic treatment (tobacco acid pyrophosphatase-alkaline phosphatase)  was translated less efficiently than untreated globin mRNA at higher K(OAc) concentrations, but retained appreciable activity at low K(OAc) concentrations."}
{"id": "PMID:209818", "title": "Effect of specific lysine modification on the reduction of cytochrome c by succinate-cytochrome c reductase.", "content": "The reduction of cytochrome c by succinate-cytochrome c reductase was studied at very low cytochrome c concentrations where the reaction between cytochrome c1 and cytochrome c was rate limiting. The rate constant for the reaction was found to be independent of ionic strength up to 0.1 M chloride, and to decrease rapidly at higher ionic strength, suggesting that the interaction between cytochrome c1 and cytochrome c was primarily electrostatic. The reaction rates of cytochrome c derivatives modified at single lysine residues to form trifluoroacetylated or trifluoromethylphenylcarbamylated cytochromes c were studied to determine the role of individual lysines in the reaction. None of the modifications affected the reaction at low ionic strength, but at higher ionic strength the reaction rate was substantially decreased by modification of those lysines surrounding the heme crevice, lysine-8, -13, -27, -72, and -79. Modification of lysine-22, -25, -55, -99, and -100 had no effect on the rate. These results indicate that the binding site on cytochrome c for cytochrome c1 overlaps considerably with that for cytochrome oxidase, suggesting that cytochrome c might undergo some type of rotational diffusion during the electron-transport process.", "contents": "Effect of specific lysine modification on the reduction of cytochrome c by succinate-cytochrome c reductase. The reduction of cytochrome c by succinate-cytochrome c reductase was studied at very low cytochrome c concentrations where the reaction between cytochrome c1 and cytochrome c was rate limiting. The rate constant for the reaction was found to be independent of ionic strength up to 0.1 M chloride, and to decrease rapidly at higher ionic strength, suggesting that the interaction between cytochrome c1 and cytochrome c was primarily electrostatic. The reaction rates of cytochrome c derivatives modified at single lysine residues to form trifluoroacetylated or trifluoromethylphenylcarbamylated cytochromes c were studied to determine the role of individual lysines in the reaction. None of the modifications affected the reaction at low ionic strength, but at higher ionic strength the reaction rate was substantially decreased by modification of those lysines surrounding the heme crevice, lysine-8, -13, -27, -72, and -79. Modification of lysine-22, -25, -55, -99, and -100 had no effect on the rate. These results indicate that the binding site on cytochrome c for cytochrome c1 overlaps considerably with that for cytochrome oxidase, suggesting that cytochrome c might undergo some type of rotational diffusion during the electron-transport process."}
{"id": "PMID:209819", "title": "Modified nucleotides in T1 RNase oligonucleotides of 18S ribosomal RNA of the Novikoff hepatoma.", "content": "The primary structure of 18S rRNA of the Novikoff hepatoma cells was investigated. Regardless of whether the primary sequence of 18S rRNA is finally determined by RNA sequencing methods or DNA sequencing methods, it is important to identify numbers and types of the modified nucleotides and accordingly the present study was designed to localize the modified regions in T1 RNase derived oligonucleotide. Modified nucleotides found in 66 different oligonucleotide sequences included 2 m62A, 1 m6A, 1 m7G, 1m1cap3psi, 7 Cm, 13 Am, 9 Gm, 11 Um, and 38 psi residues. A number of these modified nucleotides are now placed in defined sequences of T1 RNase oligonucleotides which are now being searched for in larger fragments derived from partial T1 RNase digests of 18S rRNA. Improved homochromatography fingerprinting (Choi et al. (1976) Cancer Res. 36, 4301) of T1 RNase derived oligonucleotides provided a distinctive pattern for 18S rRNA of Novikoff hepatoma ascites cells. The 116 spots obtained by homochromatography contain 176 oligonucleotide sequences.", "contents": "Modified nucleotides in T1 RNase oligonucleotides of 18S ribosomal RNA of the Novikoff hepatoma. The primary structure of 18S rRNA of the Novikoff hepatoma cells was investigated. Regardless of whether the primary sequence of 18S rRNA is finally determined by RNA sequencing methods or DNA sequencing methods, it is important to identify numbers and types of the modified nucleotides and accordingly the present study was designed to localize the modified regions in T1 RNase derived oligonucleotide. Modified nucleotides found in 66 different oligonucleotide sequences included 2 m62A, 1 m6A, 1 m7G, 1m1cap3psi, 7 Cm, 13 Am, 9 Gm, 11 Um, and 38 psi residues. A number of these modified nucleotides are now placed in defined sequences of T1 RNase oligonucleotides which are now being searched for in larger fragments derived from partial T1 RNase digests of 18S rRNA. Improved homochromatography fingerprinting (Choi et al. (1976) Cancer Res. 36, 4301) of T1 RNase derived oligonucleotides provided a distinctive pattern for 18S rRNA of Novikoff hepatoma ascites cells. The 116 spots obtained by homochromatography contain 176 oligonucleotide sequences."}
{"id": "PMID:209820", "title": "Comparative studies on the 7-iodo and 7-fluoro derivatives of N-acetoxy-N-2-acetylaminofluorene: binding sites on DNA and conformational change of modified deoxytrinucleotides.", "content": "GMP and native DNA were reacted with 7-iodo and 7-fluoro derivatives of N-acetoxy-N-2-acetylaminofluorene. It was shown that the 7-halogeno derivatives react on C-8 of guanine. Furthermore the respective amount of arylamidation (covalent linkage on the C-8 of guanine) and arylation (covalent linkage on 2-NH2 groups of C3 of guanine) addition products was determined in both native and denatured DNA-[14C]AAIF. Two G containing deoxytrinucleotides modified by either AAFF or AAIF were studied comparatively by means of circular dichroism, and as a function of several parameters known to affect the conformation of the deoxytrinucleotides. The induced optical activity in fluorofluorene ring seemed to be very sensible to the conformational changes of the deoxytrinucleotides. On the other hand, the AAIF residue exhibit a lower induced optical activity which remained unchanged when the deoxytrinucleotides conformation was affected. The results presented in this paper led us to conclude that the AAFF and AAIF modified deoxytrinucleotides adopt a conformation which nicely fits with the insertion-denaturation and outside-binding model, respectively.", "contents": "Comparative studies on the 7-iodo and 7-fluoro derivatives of N-acetoxy-N-2-acetylaminofluorene: binding sites on DNA and conformational change of modified deoxytrinucleotides. GMP and native DNA were reacted with 7-iodo and 7-fluoro derivatives of N-acetoxy-N-2-acetylaminofluorene. It was shown that the 7-halogeno derivatives react on C-8 of guanine. Furthermore the respective amount of arylamidation (covalent linkage on the C-8 of guanine) and arylation (covalent linkage on 2-NH2 groups of C3 of guanine) addition products was determined in both native and denatured DNA-[14C]AAIF. Two G containing deoxytrinucleotides modified by either AAFF or AAIF were studied comparatively by means of circular dichroism, and as a function of several parameters known to affect the conformation of the deoxytrinucleotides. The induced optical activity in fluorofluorene ring seemed to be very sensible to the conformational changes of the deoxytrinucleotides. On the other hand, the AAIF residue exhibit a lower induced optical activity which remained unchanged when the deoxytrinucleotides conformation was affected. The results presented in this paper led us to conclude that the AAFF and AAIF modified deoxytrinucleotides adopt a conformation which nicely fits with the insertion-denaturation and outside-binding model, respectively."}
{"id": "PMID:209821", "title": "Ferricytochrome c oxidation of cobaltocytochrome c. Comparison of experiments with electron-transfer theories.", "content": "Electron transfer from cobaltocytochrome c to ferricytochrome c has been studied by stopped-flow kinetics. The second-order rate constant at pH 7.0, 0.1 ionic strenght, 0.2 M phosphate, and 25 degrees C is 8.3 x 103 M-1 s-1. The activation parameters obtained from measurements made between 20 and 50 degrees C are deltaHnot equal to = 2.3 kcal mol-1 and deltaSnot equal to = -33 eu. The rate constant is not significantly dependent on ionic strength; it is also relatively independent of pH between the pK values for conformation transitions. The rate diminishes at pH greater than 12. The self-exchange reaction of cobalt cytochrome c was investigated with pulsed Fourier transform 1H NMR. The rate is too slow on the 1H NMR scale; it is estimated to be less than 133 M-1 s-1. These results together with the self-exchange rates of iron cytochrome c [Gupta, R.K., Koenig, S. H., and Redfield, A. G. (1972), J. Magn. Reson. 7, 66] were analyzed by theories of Jortner and Hopfield. The theories predict the self-exchange of Cocyt c to be too slow for 1H NMR determination. The rate constant calculated by the nonadiabatic multiphonon electron-tunneling theory for the Fecyt c-Fecyt c+ and Cocyt c-Fecyt c+ electron transfers are in good agreement with experiments.", "contents": "Ferricytochrome c oxidation of cobaltocytochrome c. Comparison of experiments with electron-transfer theories. Electron transfer from cobaltocytochrome c to ferricytochrome c has been studied by stopped-flow kinetics. The second-order rate constant at pH 7.0, 0.1 ionic strenght, 0.2 M phosphate, and 25 degrees C is 8.3 x 103 M-1 s-1. The activation parameters obtained from measurements made between 20 and 50 degrees C are deltaHnot equal to = 2.3 kcal mol-1 and deltaSnot equal to = -33 eu. The rate constant is not significantly dependent on ionic strength; it is also relatively independent of pH between the pK values for conformation transitions. The rate diminishes at pH greater than 12. The self-exchange reaction of cobalt cytochrome c was investigated with pulsed Fourier transform 1H NMR. The rate is too slow on the 1H NMR scale; it is estimated to be less than 133 M-1 s-1. These results together with the self-exchange rates of iron cytochrome c [Gupta, R.K., Koenig, S. H., and Redfield, A. G. (1972), J. Magn. Reson. 7, 66] were analyzed by theories of Jortner and Hopfield. The theories predict the self-exchange of Cocyt c to be too slow for 1H NMR determination. The rate constant calculated by the nonadiabatic multiphonon electron-tunneling theory for the Fecyt c-Fecyt c+ and Cocyt c-Fecyt c+ electron transfers are in good agreement with experiments."}
{"id": "PMID:209823", "title": "Characterization of phosphatidylthreonine in polyoma virus transformed fibroblasts.", "content": "A threonine phospholipid in polyoma virus-transformed hamster embryo fibroblasts has been characterized as phosphatidylthreonine. The identification has been made by chemical and enzymatic hydrolysis. Acid hydrolysis of the phospholipid produces free threonine. Mild alcoholysis produces a water-soluble derivative having the properties of glycerophosphorylthreonine. Hydrolysis with phospholipase C produces phosphorylthreonine which on prolonged acid hydrolysis yields threonine. Phosphatidylthreonine in the cell is more accessible to reaction with fluorodinitrobenzene than is phosphatidylserine. Phosphatidylthreonine also has been found as a major aminophospholipid in two other polyoma-transformed hamster cell lines and in the BHK-21/C13 line including the PVT-3 and TS-3 lines. the latter derived from BHK cells. Only a trace amount of phosphatidylthreonine occurs in normal liver, kidney and spleen of the adult mouse, in normal liver and kidney of the adult hamster, in whole mouse and hamster embryos, and in mouse 3T3 cells and SV40-transformed 3T3 cells.", "contents": "Characterization of phosphatidylthreonine in polyoma virus transformed fibroblasts. A threonine phospholipid in polyoma virus-transformed hamster embryo fibroblasts has been characterized as phosphatidylthreonine. The identification has been made by chemical and enzymatic hydrolysis. Acid hydrolysis of the phospholipid produces free threonine. Mild alcoholysis produces a water-soluble derivative having the properties of glycerophosphorylthreonine. Hydrolysis with phospholipase C produces phosphorylthreonine which on prolonged acid hydrolysis yields threonine. Phosphatidylthreonine in the cell is more accessible to reaction with fluorodinitrobenzene than is phosphatidylserine. Phosphatidylthreonine also has been found as a major aminophospholipid in two other polyoma-transformed hamster cell lines and in the BHK-21/C13 line including the PVT-3 and TS-3 lines. the latter derived from BHK cells. Only a trace amount of phosphatidylthreonine occurs in normal liver, kidney and spleen of the adult mouse, in normal liver and kidney of the adult hamster, in whole mouse and hamster embryos, and in mouse 3T3 cells and SV40-transformed 3T3 cells."}
{"id": "PMID:209824", "title": "Electron capture at the iron-oxygen centre in single crystals of oxymyoglobin studied by electron spin resonance spectroscopy.", "content": "Exposure of single crystals of oxy-myoglobin to 60Co gamma-rays at 77 K results in electron addition to the Fe-O2 units. The resulting ESR spectrum has been analysed to give the principal values and directions for the g-tensor of this unit. The results suggest that the dioxygen ligand is strongly tilted, the direction of tilt being close to one of the bisectors of the N-Fe-N bond angles. Possible reasons for this orientation are discussed.", "contents": "Electron capture at the iron-oxygen centre in single crystals of oxymyoglobin studied by electron spin resonance spectroscopy. Exposure of single crystals of oxy-myoglobin to 60Co gamma-rays at 77 K results in electron addition to the Fe-O2 units. The resulting ESR spectrum has been analysed to give the principal values and directions for the g-tensor of this unit. The results suggest that the dioxygen ligand is strongly tilted, the direction of tilt being close to one of the bisectors of the N-Fe-N bond angles. Possible reasons for this orientation are discussed."}
{"id": "PMID:209825", "title": "Electron addition to the active site of Cancer magister haemocyanins. An ESR study of cu(II) centres after gamma-radiolysis.", "content": "Exposure of aqueous glasses of Cancer magister haemocyanin to 60Co gamma-rays at 77 K results in a novel paramagnetic centre with ESR features showing hyperfine coupling to one strongly coupled 63/65 Cu nucleus and possibly one weakly interacting 63/65 Cu nucleus. Addition of electron scavengers showed that this centre is formed by electron addition. It is suggested that addition occurs at Cu2+-O2-Cu2+ units to give Cu2+-O2Cu+ centres. If this is correct, then electron-transfer between the two copper ions is slow or non-existent, possibly indicating that they are inequivalent. The centre is unstable, the signals being lost irreversibly on heating to approx. 270 K. The g parallel and A parallel (63/65Cu) data place this centre into the type I classification.", "contents": "Electron addition to the active site of Cancer magister haemocyanins. An ESR study of cu(II) centres after gamma-radiolysis. Exposure of aqueous glasses of Cancer magister haemocyanin to 60Co gamma-rays at 77 K results in a novel paramagnetic centre with ESR features showing hyperfine coupling to one strongly coupled 63/65 Cu nucleus and possibly one weakly interacting 63/65 Cu nucleus. Addition of electron scavengers showed that this centre is formed by electron addition. It is suggested that addition occurs at Cu2+-O2-Cu2+ units to give Cu2+-O2Cu+ centres. If this is correct, then electron-transfer between the two copper ions is slow or non-existent, possibly indicating that they are inequivalent. The centre is unstable, the signals being lost irreversibly on heating to approx. 270 K. The g parallel and A parallel (63/65Cu) data place this centre into the type I classification."}
{"id": "PMID:209826", "title": "The reaction of mercaptans with tyrosinases and hemocyanins.", "content": "1. Titration of Neurospora tyrosinase with 2-mercaptoethanol shows that the increase of absorbance at 700 nm is directly correlated to the loss of enzymatic activity. Approximately 2 mol of 2-mercaptoethanol per mole of protein are needed for full development of the green, enzymatically inactive complex. The increase of absorbance at 700 nm is also proportional to the intensity of the EPR signal and the amount of non-covalently bound 2-[35S] mercaptoethanol to the enzyme. The maximal EPR intensity reaches 70% of the protein concentration and at most 0.7--0.8 mol of 2-[35S] mercaptoethanol is bound per mol of enzyme. 2. Stopped-flow measurements show that in the reaction between 2-mercaptoethanol and Neurospora tyrosinase a raction intermediate with a strong absorption band at 360 nm is formed in an apparent second-order reaction. This intermediate displays no EPR-detectable signals. The intermediate decays in a similar complex fashion as the absorption band at 700 nm is formed. 3. The reaction of Neurospora tyrosinase with a variety of sulfhydryl compounds was also investigated. In most cases green coloured, enzymatically inactive complexes are formed displaying slightly different EPR signals. However, with cysteine and cysteamine violet coloured, enzymatically inactive complexes are formed which show rather different EPR signals. The integrated EPR intensities amount to 40--70% of the protein concentration. Based on simulations of 9 and 35 GHz spectra all observed EPR spectra can be represented as true S = 1/2 systems. The cysteamine complex can be interpreted as arising from a mixed valence Cu2+ . Cu+ complex. The 2-mercaptoethanol spectra can, however, arise from sulphur radicals. 4. Treatment of Agaricus bispora tyrosinase and Cancer pagures hemocyanin with 2-mercaptoethanol results in green-coloured, EPR detectable complexes similar to the one found with Neurospora tyrosinase. No such complexes are formed when hemocyanins from Helix pomatia and Panulirus interruptus were treated with this reagent.", "contents": "The reaction of mercaptans with tyrosinases and hemocyanins. 1. Titration of Neurospora tyrosinase with 2-mercaptoethanol shows that the increase of absorbance at 700 nm is directly correlated to the loss of enzymatic activity. Approximately 2 mol of 2-mercaptoethanol per mole of protein are needed for full development of the green, enzymatically inactive complex. The increase of absorbance at 700 nm is also proportional to the intensity of the EPR signal and the amount of non-covalently bound 2-[35S] mercaptoethanol to the enzyme. The maximal EPR intensity reaches 70% of the protein concentration and at most 0.7--0.8 mol of 2-[35S] mercaptoethanol is bound per mol of enzyme. 2. Stopped-flow measurements show that in the reaction between 2-mercaptoethanol and Neurospora tyrosinase a raction intermediate with a strong absorption band at 360 nm is formed in an apparent second-order reaction. This intermediate displays no EPR-detectable signals. The intermediate decays in a similar complex fashion as the absorption band at 700 nm is formed. 3. The reaction of Neurospora tyrosinase with a variety of sulfhydryl compounds was also investigated. In most cases green coloured, enzymatically inactive complexes are formed displaying slightly different EPR signals. However, with cysteine and cysteamine violet coloured, enzymatically inactive complexes are formed which show rather different EPR signals. The integrated EPR intensities amount to 40--70% of the protein concentration. Based on simulations of 9 and 35 GHz spectra all observed EPR spectra can be represented as true S = 1/2 systems. The cysteamine complex can be interpreted as arising from a mixed valence Cu2+ . Cu+ complex. The 2-mercaptoethanol spectra can, however, arise from sulphur radicals. 4. Treatment of Agaricus bispora tyrosinase and Cancer pagures hemocyanin with 2-mercaptoethanol results in green-coloured, EPR detectable complexes similar to the one found with Neurospora tyrosinase. No such complexes are formed when hemocyanins from Helix pomatia and Panulirus interruptus were treated with this reagent."}
{"id": "PMID:209827", "title": "A calorimetric comparison of the interaction of sodium dodecyl sulfate with cytochrome c and erythrocyte glycoproteins.", "content": "The interactions of sodium dodecyl sulfate with cytochrome c and erythrocyte glycoproteins have been studied by the method of titration calorimetry. It was found that the initial addition of sodium dodecyl sulfate to cytochrome c caused an endothermic unfolding of the protein, detectable by circular dichroism (CD). This was followed by the exothermic binding of sodium dodecyl sulfate to the protein, without further CD-detectable conformational changes. In contrast, sodium dodecyl sulfate bound directly to the erythrocyte glycoproteins in an exothermic reaction without any accompanying CD-detectable conformation changes. This indicates that the glycoproteins solubilized in aqueous media have exposed hydrophobic regions which can interact directly with this detergent. The enthalpy changes and stoichiometries of binding are reported.", "contents": "A calorimetric comparison of the interaction of sodium dodecyl sulfate with cytochrome c and erythrocyte glycoproteins. The interactions of sodium dodecyl sulfate with cytochrome c and erythrocyte glycoproteins have been studied by the method of titration calorimetry. It was found that the initial addition of sodium dodecyl sulfate to cytochrome c caused an endothermic unfolding of the protein, detectable by circular dichroism (CD). This was followed by the exothermic binding of sodium dodecyl sulfate to the protein, without further CD-detectable conformational changes. In contrast, sodium dodecyl sulfate bound directly to the erythrocyte glycoproteins in an exothermic reaction without any accompanying CD-detectable conformation changes. This indicates that the glycoproteins solubilized in aqueous media have exposed hydrophobic regions which can interact directly with this detergent. The enthalpy changes and stoichiometries of binding are reported."}
{"id": "PMID:209828", "title": "[Binding of spin-labeled palmitic acid by bovine serum albumin].", "content": "Investigation of the binding of spin-labeled palmitic acid and its esters with bovine serum albumin is presented. Both probes are shown to bind strictly to strongly and loosely binding centers of protein. The quantitative study allows to determine the binding constant and number of protein binding sites. It is found that the total binding constant for esterified derivative is several times as much as that of palmitic acid.", "contents": "[Binding of spin-labeled palmitic acid by bovine serum albumin]. Investigation of the binding of spin-labeled palmitic acid and its esters with bovine serum albumin is presented. Both probes are shown to bind strictly to strongly and loosely binding centers of protein. The quantitative study allows to determine the binding constant and number of protein binding sites. It is found that the total binding constant for esterified derivative is several times as much as that of palmitic acid."}
{"id": "PMID:209835", "title": "Long-lasting effect of single ecdysone injections in newborn rats.", "content": "Single injections of ecdysone to newborn rats were followed by increases in the weights of the adrenals and decreases in the weights of the thymuses in the adults. No change was registered in body weights and in the weights of the gonads. The plasma androsterone levels seemed to decrease; however, the interindividual differences proved to be too great to draw definite conclusions.", "contents": "Long-lasting effect of single ecdysone injections in newborn rats. Single injections of ecdysone to newborn rats were followed by increases in the weights of the adrenals and decreases in the weights of the thymuses in the adults. No change was registered in body weights and in the weights of the gonads. The plasma androsterone levels seemed to decrease; however, the interindividual differences proved to be too great to draw definite conclusions."}
{"id": "PMID:209836", "title": "The conversion of aryl sulfate ester salts to alkyl aryl derivatives suitable for analysis by electron impact mass spectrometry.", "content": "A series of monosubstituted (CH3, CH3O, Cl Br or NO2 at the O, m and p position) phenyl sulfate ester salts were derivatized to form n-propyl aryl sulfate diesters. The derivatization was accomplished by reacting aryl sulfate ester salts, AgClO4 and n-propyl iodide in SO2 at--40 degree C. The mass spectra of all the n-propyl aryl sulfate esters showed an intense molecular ion and intense diagnostic peaks at M--42 ([aryl--OSO3H]+) and M--122 ([ARYL--OH]+). The utility of this procedure for derivatizing selected sulfate ester conjugated xenobiotics and steroids was demonstrated.", "contents": "The conversion of aryl sulfate ester salts to alkyl aryl derivatives suitable for analysis by electron impact mass spectrometry. A series of monosubstituted (CH3, CH3O, Cl Br or NO2 at the O, m and p position) phenyl sulfate ester salts were derivatized to form n-propyl aryl sulfate diesters. The derivatization was accomplished by reacting aryl sulfate ester salts, AgClO4 and n-propyl iodide in SO2 at--40 degree C. The mass spectra of all the n-propyl aryl sulfate esters showed an intense molecular ion and intense diagnostic peaks at M--42 ([aryl--OSO3H]+) and M--122 ([ARYL--OH]+). The utility of this procedure for derivatizing selected sulfate ester conjugated xenobiotics and steroids was demonstrated."}
{"id": "PMID:209832", "title": "[Photoinduced peroxidase reduction. Reaction with indolylacetic acid].", "content": "Kinetics of photoinduced reaction of HRP reduction by indolil acetic acid and dependence of the reaction rate and fluorescence of indoliol acetic acid on quenchers (I, Cst concentration was investigated. It was demonstrated that both I- and Cst action on the reaction differed from that on fluorescence. So the most probable reaction pathway is that through metastable triplet state of the substrate.", "contents": "[Photoinduced peroxidase reduction. Reaction with indolylacetic acid]. Kinetics of photoinduced reaction of HRP reduction by indolil acetic acid and dependence of the reaction rate and fluorescence of indoliol acetic acid on quenchers (I, Cst concentration was investigated. It was demonstrated that both I- and Cst action on the reaction differed from that on fluorescence. So the most probable reaction pathway is that through metastable triplet state of the substrate."}
{"id": "PMID:209837", "title": "[Enzymes of tissue respiration and oxidative phosphorylation in the myocardium after neurogenic damage to it].", "content": "Three-hour electrical stimulation of the aortic arch in the rabbit myocardium is followed by a marked increase of the succinate dehydrogenase activity, by a sharp fall of the cytochrome oxidase activity and by uncoupling of the oxidation and phosphorylation processes. It is suggested that neurogenic myocardial damage is accompanied by discoordination in the energy processes regulation with uncoupling of the oxidative phosphorylation and by a decrease of the macroergic compounds synthesis.", "contents": "[Enzymes of tissue respiration and oxidative phosphorylation in the myocardium after neurogenic damage to it]. Three-hour electrical stimulation of the aortic arch in the rabbit myocardium is followed by a marked increase of the succinate dehydrogenase activity, by a sharp fall of the cytochrome oxidase activity and by uncoupling of the oxidation and phosphorylation processes. It is suggested that neurogenic myocardial damage is accompanied by discoordination in the energy processes regulation with uncoupling of the oxidative phosphorylation and by a decrease of the macroergic compounds synthesis."}
{"id": "PMID:209829", "title": "[Effect of perturbing agents on the dynamic properties of immunoglobulin fragments].", "content": "The effect of NaCl, (NH4)2SO4, sodium dodecylsulphate and temperature on conformational properties of light-chain dimers and the Fab-fragments of immunoglobulins G has been investigated using the spin-label method. All these agents despite their different nature, induce qualitatively the same shift in the equilibrium between the A- and B-states of spin label towards the state of higher microviscosity A. The effect of 1.2 M NaCl and 0.75 M (NH4)2SO4 increase the stability of IgG in relation to temperature, as a result of this shift. The data obtained are interpreted in terms of the dynamic model of protein behaviour in water suggested earlier. In accordance with the model the action of the agents perturbing the conformation of protein and the ordered structure of water in the non-polar cavities of protein, reduce the life-time of this cavities in the water accessible state.", "contents": "[Effect of perturbing agents on the dynamic properties of immunoglobulin fragments]. The effect of NaCl, (NH4)2SO4, sodium dodecylsulphate and temperature on conformational properties of light-chain dimers and the Fab-fragments of immunoglobulins G has been investigated using the spin-label method. All these agents despite their different nature, induce qualitatively the same shift in the equilibrium between the A- and B-states of spin label towards the state of higher microviscosity A. The effect of 1.2 M NaCl and 0.75 M (NH4)2SO4 increase the stability of IgG in relation to temperature, as a result of this shift. The data obtained are interpreted in terms of the dynamic model of protein behaviour in water suggested earlier. In accordance with the model the action of the agents perturbing the conformation of protein and the ordered structure of water in the non-polar cavities of protein, reduce the life-time of this cavities in the water accessible state."}
{"id": "PMID:209838", "title": "[Hepatic adenosine-3',5'-monophosphate metabolism in newborn rats irradiated during the period of organogenesis].", "content": "The adenylate cylcase (AC) and phosphodiesterase (PDE) activities, as well as the 3'5'-AMP (cAMP) fund were studied in the liver of newborn rats, intact, and after irradiation on the 9th day of the embryonic development. A decrease of AC and PDE activities was noted with a dose of 50 r. The stationary level of cAMP in the tissue remained unchanged. The adrenaline-stimulated AC activity only tended to decrease in case of irradiation. As suggested, during critical periods of development, in the presence of the hormone inductor in the liver of irradiated rats, conditions can be created for an increase of the cAMP pool.", "contents": "[Hepatic adenosine-3',5'-monophosphate metabolism in newborn rats irradiated during the period of organogenesis]. The adenylate cylcase (AC) and phosphodiesterase (PDE) activities, as well as the 3'5'-AMP (cAMP) fund were studied in the liver of newborn rats, intact, and after irradiation on the 9th day of the embryonic development. A decrease of AC and PDE activities was noted with a dose of 50 r. The stationary level of cAMP in the tissue remained unchanged. The adrenaline-stimulated AC activity only tended to decrease in case of irradiation. As suggested, during critical periods of development, in the presence of the hormone inductor in the liver of irradiated rats, conditions can be created for an increase of the cAMP pool."}
{"id": "PMID:209830", "title": "[Spin glass type structures in chloroplasts].", "content": "The nature of discovered in [2] magnetic anisotropy of ESR signal with g approximately 3 appearing in chloroplasts at helium temperatures has been studied and clarified. It was found that a signal with these properties can arise only when dark adapted chloroplasts are cooled down to temperatures lower than 23 K in an external magnetic field (Ho greater than 2.300 Oe). The results obtained indicate that the system studied belongs to the type of \"spin glasses\", i. e., of the magnetically diluted structures with cooperative magnetic interaction between centres. These cooperative properties can be most distinctly observed at definite temperature and magnetic field strength values.", "contents": "[Spin glass type structures in chloroplasts]. The nature of discovered in [2] magnetic anisotropy of ESR signal with g approximately 3 appearing in chloroplasts at helium temperatures has been studied and clarified. It was found that a signal with these properties can arise only when dark adapted chloroplasts are cooled down to temperatures lower than 23 K in an external magnetic field (Ho greater than 2.300 Oe). The results obtained indicate that the system studied belongs to the type of \"spin glasses\", i. e., of the magnetically diluted structures with cooperative magnetic interaction between centres. These cooperative properties can be most distinctly observed at definite temperature and magnetic field strength values."}
{"id": "PMID:209839", "title": "Platelet release reaction and intracellular cGMP.", "content": "Enchanced cAMP concentrations inhibit the aggregation and release reaction of isolated human platelets and platelet-rich plasma to all known inducing agents. An opposing role for cGMP in this phenomenon has been proposed by some but not by others, and the function of cGMP in this secretory process is unclear. To further elucidate the role of cGMP in the release reaction, the effect of increased concentrations of this cyclic nucleotide on 14C-serotonin release was evaluated utilizing isolated human platelets and highly purified human thrombin or commercially available bovine thrombin. Several recently described stimulators of guanylate cyclase, including sodium nitroprusside, sodium azide, nitrosoquanidines, and ascorbic acid, were found to markedly augment platelet cGMP levels. Enhanced platelet cGMP concentrations produced by these drugs or by the exogenous addition of cGMP and its analogues neither caused these cells to secrete nor modulated the thrombin-induced serotonin release reaction. The inhibition of serotonin release by increased cAMP concentrations was not counteracted by increased cGMP levels. Platelet cGMP concentrations were unaltered by thrombin. These data indicate that cGMP is not an obligatory signal or a modulator of the thrombin-induced platelet release reaction.", "contents": "Platelet release reaction and intracellular cGMP. Enchanced cAMP concentrations inhibit the aggregation and release reaction of isolated human platelets and platelet-rich plasma to all known inducing agents. An opposing role for cGMP in this phenomenon has been proposed by some but not by others, and the function of cGMP in this secretory process is unclear. To further elucidate the role of cGMP in the release reaction, the effect of increased concentrations of this cyclic nucleotide on 14C-serotonin release was evaluated utilizing isolated human platelets and highly purified human thrombin or commercially available bovine thrombin. Several recently described stimulators of guanylate cyclase, including sodium nitroprusside, sodium azide, nitrosoquanidines, and ascorbic acid, were found to markedly augment platelet cGMP levels. Enhanced platelet cGMP concentrations produced by these drugs or by the exogenous addition of cGMP and its analogues neither caused these cells to secrete nor modulated the thrombin-induced serotonin release reaction. The inhibition of serotonin release by increased cAMP concentrations was not counteracted by increased cGMP levels. Platelet cGMP concentrations were unaltered by thrombin. These data indicate that cGMP is not an obligatory signal or a modulator of the thrombin-induced platelet release reaction."}
{"id": "PMID:209840", "title": "[Contribution of immunohistochemistry to the cytological study of the adenohypophysis].", "content": "In the first chapter, the initial studies using immuno-histochemical methods for the cytological analysis of the adenohypophysis are presented; the different trends of the actual groups of research workers are summarized. In the second chapter are described, with details utillsation, some ser viceable techniques for experimental or anatomo-pathological studies of the pituitary gland; immunization of animals against hypophysial hormones, application to the study of the hypophysis (conditions of fixation, analysis of the subsequent times of histological techniques, immunohistochemical reactions [immuno-fluorescence and immuno-enzymatic reactions], controls of these reactions, applications on semi-thin and ultra-thin sections). In the third charpter are studied the results of this immunohistochemical analysis of the mammalian hypophysis: description of different cell types first in the anterior lobe then in the intermediate lobe; these observations are discussed. A special subdivision concerns the study of the human pituitary gland in normal and pathological conditions, in adults and foetuses. In the fourth chapter the results obtained in the study of the adenohypophysis of non mammalian Vertebrates: Fish, Amphibians, Reptiles, and Birds, are grouped. An extensive bibliography concludes this review (references until 1977). Illustrations, furnished by several french workers, are adapted to the different descriptions.", "contents": "[Contribution of immunohistochemistry to the cytological study of the adenohypophysis]. In the first chapter, the initial studies using immuno-histochemical methods for the cytological analysis of the adenohypophysis are presented; the different trends of the actual groups of research workers are summarized. In the second chapter are described, with details utillsation, some ser viceable techniques for experimental or anatomo-pathological studies of the pituitary gland; immunization of animals against hypophysial hormones, application to the study of the hypophysis (conditions of fixation, analysis of the subsequent times of histological techniques, immunohistochemical reactions [immuno-fluorescence and immuno-enzymatic reactions], controls of these reactions, applications on semi-thin and ultra-thin sections). In the third charpter are studied the results of this immunohistochemical analysis of the mammalian hypophysis: description of different cell types first in the anterior lobe then in the intermediate lobe; these observations are discussed. A special subdivision concerns the study of the human pituitary gland in normal and pathological conditions, in adults and foetuses. In the fourth chapter the results obtained in the study of the adenohypophysis of non mammalian Vertebrates: Fish, Amphibians, Reptiles, and Birds, are grouped. An extensive bibliography concludes this review (references until 1977). Illustrations, furnished by several french workers, are adapted to the different descriptions."}
{"id": "PMID:209843", "title": "Treatment of oat cell carcinoma of the lung: complete remissions, acceptable complications, and improved survival.", "content": "Oat cell lung cancer is a common disease which is usually disseminated by the time it is diagnosed. Treatment with cyclic combination chemotherapy (cyclophosphamide, doxorubicin, vincristine) administered concurrently with radiotherapy to the chest lesion and subsequent prophylactic brain irradiation was investigated in 36 patients with oat-cell carcinoma of the lung. Complete remissions occurred in 26 of the patients (15 of the 16 with limited-stage disease and 11 of the 20 with extensive-stage disease). Symptomatic improvement occurred in all patients. Twelve of the 16 patients with limited disease remained well and free of disease for over a year. The results were equivalent to those of a similar though more intensive regimen, but the toxicity was much less (there were no treatment-related deaths). Transient granulocytopenia with the risk of infection was the most serious complication. Survival and quality of life have been improved for all patients, particularly those with limited disease, who have previously responded poorly to treatment.", "contents": "Treatment of oat cell carcinoma of the lung: complete remissions, acceptable complications, and improved survival. Oat cell lung cancer is a common disease which is usually disseminated by the time it is diagnosed. Treatment with cyclic combination chemotherapy (cyclophosphamide, doxorubicin, vincristine) administered concurrently with radiotherapy to the chest lesion and subsequent prophylactic brain irradiation was investigated in 36 patients with oat-cell carcinoma of the lung. Complete remissions occurred in 26 of the patients (15 of the 16 with limited-stage disease and 11 of the 20 with extensive-stage disease). Symptomatic improvement occurred in all patients. Twelve of the 16 patients with limited disease remained well and free of disease for over a year. The results were equivalent to those of a similar though more intensive regimen, but the toxicity was much less (there were no treatment-related deaths). Transient granulocytopenia with the risk of infection was the most serious complication. Survival and quality of life have been improved for all patients, particularly those with limited disease, who have previously responded poorly to treatment."}
{"id": "PMID:209847", "title": "Recurrent genital herpes among women: symptomatic v. asymptomatic viral shedding.", "content": "To investigate whether asymptomatic shedding of herpes simplex virus occurs in women with recurrent genital herpes, six women with documented disease were followed up twice weekly with viral cultures and pelvic examination. During the study period of 1330 patient days and 452 patient visits, 26 episodes of genital herpesvirus infection were recorded. Twenty-three (88%) episodes were accompanied by signs and symptoms. Three (14%) of the culture-positive recurrences were asymptomatic. In one episode an asymptomatic lesion was noted, and in two instances viral shedding from the vulva or cervix occurred in the absence of visible herpetic lesions. Three of the six women had evidence of recurrent cervical herpesvirus infection. No relationships between menstrual cycle and sexual activity and the onset of recurrence were noted.", "contents": "Recurrent genital herpes among women: symptomatic v. asymptomatic viral shedding. To investigate whether asymptomatic shedding of herpes simplex virus occurs in women with recurrent genital herpes, six women with documented disease were followed up twice weekly with viral cultures and pelvic examination. During the study period of 1330 patient days and 452 patient visits, 26 episodes of genital herpesvirus infection were recorded. Twenty-three (88%) episodes were accompanied by signs and symptoms. Three (14%) of the culture-positive recurrences were asymptomatic. In one episode an asymptomatic lesion was noted, and in two instances viral shedding from the vulva or cervix occurred in the absence of visible herpetic lesions. Three of the six women had evidence of recurrent cervical herpesvirus infection. No relationships between menstrual cycle and sexual activity and the onset of recurrence were noted."}
{"id": "PMID:209849", "title": "Characterization of the retrograde transport of nerve growth factor (NGF) using high specific activity [125I] NGF.", "content": "The process of the retrograde transport of nerve growth factor (NGF) has been recharacterized using a high specific activity preparation of[125I]NGF. Most of the general conclusions reached in the previous studies of Hendry, Thoenen and co-workers have been confirmed. However, significant quantitative differences were noted. Intraocular (anterior eye chamber) administration of[125I]NGF (less than 10 ng) resulted in accumulation in the superior cervical ganglia beginning at about 4 h. The ratio of radioactivity in the ipsilateral contralateral ganglia was 15--30:1. Maximal accumulation was seen at about 12h in the hamster and 16 h in rats. This pattern was quite different from that seen in other tissues. The uptake system from the eye of the rat was saturable (half-maximal at 15 ng) with maximal accumulation of 35--40 pg/ganglion. Systemic administration of[125I]NGF (200 ng) to adult rats resulted in no accumulation in SGG or celiac ganglion prior to 3 h, with subsequent rapid accumulation by 6 h and a rapid fall in radioactivity after 12 h. A similar time course was seen in 5-day-old rats, although the time curve was shifted slightly toward shorter time. The radioactivity in ganglia co-migrated with native NGF by SDS gell electrophoresis. Cytochrome c of comparable specific activity was not transported, and NGF did not stimulate the uptake and transport of cytochrome c. The retrograde transport of[125I]NGF was inhibited by the co-administration of biologically active, but not inactive, oxidized derivatives of NGF. By any route of administration, a significant percentage of the transported[125I]NGF was found in a purified nuclear fraction of the ganglia. Coupled with previous observations of specific nuclear NGF receptors in embryonic chick and sympathetic ganglia, this suggests that, after internalization and retrograde transport, NGF may directly act on the nucleus to produce at least some of its effects on the responsive cell.", "contents": "Characterization of the retrograde transport of nerve growth factor (NGF) using high specific activity [125I] NGF. The process of the retrograde transport of nerve growth factor (NGF) has been recharacterized using a high specific activity preparation of[125I]NGF. Most of the general conclusions reached in the previous studies of Hendry, Thoenen and co-workers have been confirmed. However, significant quantitative differences were noted. Intraocular (anterior eye chamber) administration of[125I]NGF (less than 10 ng) resulted in accumulation in the superior cervical ganglia beginning at about 4 h. The ratio of radioactivity in the ipsilateral contralateral ganglia was 15--30:1. Maximal accumulation was seen at about 12h in the hamster and 16 h in rats. This pattern was quite different from that seen in other tissues. The uptake system from the eye of the rat was saturable (half-maximal at 15 ng) with maximal accumulation of 35--40 pg/ganglion. Systemic administration of[125I]NGF (200 ng) to adult rats resulted in no accumulation in SGG or celiac ganglion prior to 3 h, with subsequent rapid accumulation by 6 h and a rapid fall in radioactivity after 12 h. A similar time course was seen in 5-day-old rats, although the time curve was shifted slightly toward shorter time. The radioactivity in ganglia co-migrated with native NGF by SDS gell electrophoresis. Cytochrome c of comparable specific activity was not transported, and NGF did not stimulate the uptake and transport of cytochrome c. The retrograde transport of[125I]NGF was inhibited by the co-administration of biologically active, but not inactive, oxidized derivatives of NGF. By any route of administration, a significant percentage of the transported[125I]NGF was found in a purified nuclear fraction of the ganglia. Coupled with previous observations of specific nuclear NGF receptors in embryonic chick and sympathetic ganglia, this suggests that, after internalization and retrograde transport, NGF may directly act on the nucleus to produce at least some of its effects on the responsive cell."}
{"id": "PMID:209850", "title": "Direct mapping of beta-adrenergic receptors in the rat central nervous system by a novel fluorescent beta-blocker.", "content": "DL-N-(2-Hydroxy-3-napthyloxypropyl)-N'-dansylethylenediamine, dansyl analogue of propranolol (DAPN) is a novel fluorescent beta-adrenergic antagonist with high affinity to beta-receptors. The distribution pattern of DAPN fluorescence was studied in the rat central nervous system subsequent to its intravenous administration to living rats. DAPN distinctly labels specific regions and cells in the central nervous system (CNS). Highly dense DAPN fluorescence was observed in the pyramidal cell layer of the hippocampus, the granule cell layer of the dentate gyrus, the basal layers of the piriform cortex and the neocortex, the cerebellar Purkinje cell layer, and the spinal a-motoneurons. Pretreatment of control rats with DL-and L-propranolol markedly decreased the intensity and density of DAPN fluorescence in the tissue sections, whereas prior administration of D-propranolol had almost no effect. Pretreatment with large doses of reserpine did not alter the pattern of DAPN fluorescence. These findings were identical to those observed with another fluorescent beta-blocker, 9-aminoacridino-propranolol (9-AAP). Our data suggest that fluorescent beta-adrenergic antagonists may be used in vivo for the direct probing of the beta-receptors within the mammalian CNS.", "contents": "Direct mapping of beta-adrenergic receptors in the rat central nervous system by a novel fluorescent beta-blocker. DL-N-(2-Hydroxy-3-napthyloxypropyl)-N'-dansylethylenediamine, dansyl analogue of propranolol (DAPN) is a novel fluorescent beta-adrenergic antagonist with high affinity to beta-receptors. The distribution pattern of DAPN fluorescence was studied in the rat central nervous system subsequent to its intravenous administration to living rats. DAPN distinctly labels specific regions and cells in the central nervous system (CNS). Highly dense DAPN fluorescence was observed in the pyramidal cell layer of the hippocampus, the granule cell layer of the dentate gyrus, the basal layers of the piriform cortex and the neocortex, the cerebellar Purkinje cell layer, and the spinal a-motoneurons. Pretreatment of control rats with DL-and L-propranolol markedly decreased the intensity and density of DAPN fluorescence in the tissue sections, whereas prior administration of D-propranolol had almost no effect. Pretreatment with large doses of reserpine did not alter the pattern of DAPN fluorescence. These findings were identical to those observed with another fluorescent beta-blocker, 9-aminoacridino-propranolol (9-AAP). Our data suggest that fluorescent beta-adrenergic antagonists may be used in vivo for the direct probing of the beta-receptors within the mammalian CNS."}
{"id": "PMID:209856", "title": "Binding assay for opioid peptides with neuroblastoma x glioma hybrid cells: specificity of the receptor site.", "content": "A sensitive and rapid radioreceptor assay has been developed to monitor opioid peptides in column effluents. It is based on competitive binding to NG 108-15 cells using [3H-Tyr]Leu-enkephalin as the displaced ligand. The specificity of binding to the cells of naturally occurring opioid peptides and synthetic analogs has been shown to be similar to that found with synaptic plasma membranes.", "contents": "Binding assay for opioid peptides with neuroblastoma x glioma hybrid cells: specificity of the receptor site. A sensitive and rapid radioreceptor assay has been developed to monitor opioid peptides in column effluents. It is based on competitive binding to NG 108-15 cells using [3H-Tyr]Leu-enkephalin as the displaced ligand. The specificity of binding to the cells of naturally occurring opioid peptides and synthetic analogs has been shown to be similar to that found with synaptic plasma membranes."}
{"id": "PMID:209862", "title": "Electrophysiological demonstration of an excitatory subthalamonigral pathway in the rat.", "content": "The subthalamonigral projection was studied with extracellular techniques in the rat. Orthodromic and antidromic stimulations of this pathway were performed in different sets of experiments in order to exclude the possible activation of passing fibers. A majority of the recorded cells in the subthalamic nucleus (STN) were antidromically activated by nigral stimulation. It was furthermore shown that the subthalamofugal fibers are excitatory to cells located in the pars compacta as well as in the pars reticulata of the substantia nigra. The possible existence of another descending STN pathway is also discussed.", "contents": "Electrophysiological demonstration of an excitatory subthalamonigral pathway in the rat. The subthalamonigral projection was studied with extracellular techniques in the rat. Orthodromic and antidromic stimulations of this pathway were performed in different sets of experiments in order to exclude the possible activation of passing fibers. A majority of the recorded cells in the subthalamic nucleus (STN) were antidromically activated by nigral stimulation. It was furthermore shown that the subthalamofugal fibers are excitatory to cells located in the pars compacta as well as in the pars reticulata of the substantia nigra. The possible existence of another descending STN pathway is also discussed."}
{"id": "PMID:209863", "title": "Participation of limbic-hypothalamic structures in circadian rhythm of slow wave sleep and paradoxical sleep in the rat.", "content": "The effect of brain lesion or surgical isolation of the neural circuit on SWS and PS circadian rhythm have been studied in female rats under a 14/10 light-dark schedule. Cortical EEG'S AND DORSAL NECK EMG were used to monitor SWS, PS and alertness in female rats. Intact and operated controls showed regular 4-5-day vaginal cycles and nocturnal sleep rhythm, but the night PS value on proestrus was lower than in other cycles. Following septal lesion, MPO roof cut, vaginal cycles and SWS rhythm were regularly maintained; however, the PS appearance at night, except during proestrus, increased (night PS peak). These results were similar to those for pinealectomized or ovariectomized female rats. A frontal cut of the MBH produced persistent estrus and disturbed both SWS and PS circadian rhythm. The suprachiasmatic-lesioned rats showed persistent estrus and disrupted SWS rhythm, but regularly maintained the circadian PS rhythm. The vaginal cycles and SWS rhythm in the fornical-transected rats were regularly maintained, but the PS rhythm was disturbed during diestrus and showed ultradian rhythm. From these results, it is suggested that the pineal hormone and the gonadal feedback mechanisms may be involved in the night PS peak and this mechanism may involve the septal- and amygdaloid-hypothalamic systems. A different neural mechanism exist for SWS and PS circadian rhythm; SWS rhythm involves the suprachiasmatic-basal hypothalamic system and PS circadian rhythm is related, in part, to the hippocampal-hypothalamic system.", "contents": "Participation of limbic-hypothalamic structures in circadian rhythm of slow wave sleep and paradoxical sleep in the rat. The effect of brain lesion or surgical isolation of the neural circuit on SWS and PS circadian rhythm have been studied in female rats under a 14/10 light-dark schedule. Cortical EEG'S AND DORSAL NECK EMG were used to monitor SWS, PS and alertness in female rats. Intact and operated controls showed regular 4-5-day vaginal cycles and nocturnal sleep rhythm, but the night PS value on proestrus was lower than in other cycles. Following septal lesion, MPO roof cut, vaginal cycles and SWS rhythm were regularly maintained; however, the PS appearance at night, except during proestrus, increased (night PS peak). These results were similar to those for pinealectomized or ovariectomized female rats. A frontal cut of the MBH produced persistent estrus and disturbed both SWS and PS circadian rhythm. The suprachiasmatic-lesioned rats showed persistent estrus and disrupted SWS rhythm, but regularly maintained the circadian PS rhythm. The vaginal cycles and SWS rhythm in the fornical-transected rats were regularly maintained, but the PS rhythm was disturbed during diestrus and showed ultradian rhythm. From these results, it is suggested that the pineal hormone and the gonadal feedback mechanisms may be involved in the night PS peak and this mechanism may involve the septal- and amygdaloid-hypothalamic systems. A different neural mechanism exist for SWS and PS circadian rhythm; SWS rhythm involves the suprachiasmatic-basal hypothalamic system and PS circadian rhythm is related, in part, to the hippocampal-hypothalamic system."}
{"id": "PMID:209864", "title": "The clearing of excess potassium from extracellular space in spinal cord and cerebral cortex.", "content": "The relative importance of active and passive transport processes in the clearing of potassium released from active neurons was estimated Extracellular potassium activity [K+]0 was measured with ion-selective microelectrodes in the sensory area of the neocortex and in lumbosacral spinal cord of cats. Transient elevation of [K+]0 was evoked in cortex by stimulation of VPL and in spinal cord by stimulation of afferent nerves. The rate with which excess [K+]0 was cleared was either feebly or not at all influenced by variation of the intensity and frequency of stimulation. The half-decay times of [K+]0 were however prolonged when the duration of stimulus trains was increased. Only small differences were seen in the rate of decay of [K+]0 transients recorded at different locations within the gray matter; the shortest half-decay times occurred where K+ responses were largest. The different profiles of distribution of delta [K+]0 in response to stimulation of the cortical surface and of VPL nucleus were mapped. As in spinal cord also in cortex the distribution of the evoked sustained shifts of electric potential mirrored the distribution of [K+]0 transients. The rate at which K+ could diffuse out of volume sources similar in magnitude to the volumes of distribution of [K+]0 responses in gray matter were calculated. The observed half-decay times of [K+]0 transients were more than a hundred times shorter than those calculated for diffusion either in spinal cord or in cortex. Intravenous administration of digitoxigenin was shown to retard the clearing of [K+]0 and caused an elevation of the unstimulated [K+]0 baseline. Seizures were frequently induced by digitoxigenin when the [K+]0 baseline was only slightly elevated, and the occurrence of seizures was not associated with a definable threshold level of [K+]0. It is concluded that active reuptake is the principal mechanism of the clearing of [K+]0 released by neurons. Redistribution of K+ by diffusion must have been negligible under the conditions of these experiments, but may be more important when only a few neurons release K+ amongst many inactive cells. Considerations of a glial transport network are probably inconsequential for theories of the generation of seizures.", "contents": "The clearing of excess potassium from extracellular space in spinal cord and cerebral cortex. The relative importance of active and passive transport processes in the clearing of potassium released from active neurons was estimated Extracellular potassium activity [K+]0 was measured with ion-selective microelectrodes in the sensory area of the neocortex and in lumbosacral spinal cord of cats. Transient elevation of [K+]0 was evoked in cortex by stimulation of VPL and in spinal cord by stimulation of afferent nerves. The rate with which excess [K+]0 was cleared was either feebly or not at all influenced by variation of the intensity and frequency of stimulation. The half-decay times of [K+]0 were however prolonged when the duration of stimulus trains was increased. Only small differences were seen in the rate of decay of [K+]0 transients recorded at different locations within the gray matter; the shortest half-decay times occurred where K+ responses were largest. The different profiles of distribution of delta [K+]0 in response to stimulation of the cortical surface and of VPL nucleus were mapped. As in spinal cord also in cortex the distribution of the evoked sustained shifts of electric potential mirrored the distribution of [K+]0 transients. The rate at which K+ could diffuse out of volume sources similar in magnitude to the volumes of distribution of [K+]0 responses in gray matter were calculated. The observed half-decay times of [K+]0 transients were more than a hundred times shorter than those calculated for diffusion either in spinal cord or in cortex. Intravenous administration of digitoxigenin was shown to retard the clearing of [K+]0 and caused an elevation of the unstimulated [K+]0 baseline. Seizures were frequently induced by digitoxigenin when the [K+]0 baseline was only slightly elevated, and the occurrence of seizures was not associated with a definable threshold level of [K+]0. It is concluded that active reuptake is the principal mechanism of the clearing of [K+]0 released by neurons. Redistribution of K+ by diffusion must have been negligible under the conditions of these experiments, but may be more important when only a few neurons release K+ amongst many inactive cells. Considerations of a glial transport network are probably inconsequential for theories of the generation of seizures."}
{"id": "PMID:209870", "title": "Lateral geniculate cell responses to electrical stimulation of the retina.", "content": "Electrical stimulation of the retina evokes at the optic tract level rhythmic bursts of activity whose temporal structure is predictable from the polarity of the stimulation and the receptive field type. The reaction of lateral geniculate units to this input was studied in fast and slow relay cells as well as in interneurons. The results revealed that fast relaty cells presented a response whose temporal structure remained essentially unmodified in comparison to that observed at the optic tract level: that both anodal and cathodal polarities produced rythmic pattern of excitation the latency of which depended upon receptive field type and polarity applied. In slow relay cells and interneurons responses with equal latencies could be evoked for both polarities. Following cortical depression with 3 M KCl the latency of first bursts was unaffected in relay cells, while about one third of interneurons showed a temporal pattern which was similar to that recorded at the optic tract level after the treatment. This suggests that both ON and OFF retinal networks converge upon one geniculate slow P cell and interneuron, whereas fast relay cells are mostly driven by one of the two systems. Furthermore this convergence may be achieved through visual cortex in some units.", "contents": "Lateral geniculate cell responses to electrical stimulation of the retina. Electrical stimulation of the retina evokes at the optic tract level rhythmic bursts of activity whose temporal structure is predictable from the polarity of the stimulation and the receptive field type. The reaction of lateral geniculate units to this input was studied in fast and slow relay cells as well as in interneurons. The results revealed that fast relaty cells presented a response whose temporal structure remained essentially unmodified in comparison to that observed at the optic tract level: that both anodal and cathodal polarities produced rythmic pattern of excitation the latency of which depended upon receptive field type and polarity applied. In slow relay cells and interneurons responses with equal latencies could be evoked for both polarities. Following cortical depression with 3 M KCl the latency of first bursts was unaffected in relay cells, while about one third of interneurons showed a temporal pattern which was similar to that recorded at the optic tract level after the treatment. This suggests that both ON and OFF retinal networks converge upon one geniculate slow P cell and interneuron, whereas fast relay cells are mostly driven by one of the two systems. Furthermore this convergence may be achieved through visual cortex in some units."}
{"id": "PMID:209871", "title": "Electrophysiological changes induced by paradoxical sleep deprivation and lithium chloride poisoning in rats.", "content": "In an attempt to analyze the disruption of conditioned taste aversion (CTA) caused by pre-acquisition paradoxical sleep deprivation (PSD), the effect of poisoning (0.15 M LiCl, 4% body weight) on the sleep--wakefulness pattern was studied in 12 rats with chronically implanted electrodes. The polygraphic recording showed that poisoning reduced the total sleep time in the subsequent 3 h from 57 to 42% and REM sleep from 6 to 2%. The lithium chloride effect was still more pronounced after 24-h REM sleep deprivation: the total sleep time decreased from 67 to 46% and REM sleep from 13 to 2%. The change of sleep--wakefulness pattern, most pronounced during the first hour of poisoning, gradually returned to normal but REM sleep was significantly reduced even 3 h after poisoning. It is concluded that 24-h PSD does not alleviate the subsequent poisoning. On the other hand, the lithium chloride induced reduction of post-acquisition REM sleep many enhance the learning impairment caused by pre-acquisition PSD.", "contents": "Electrophysiological changes induced by paradoxical sleep deprivation and lithium chloride poisoning in rats. In an attempt to analyze the disruption of conditioned taste aversion (CTA) caused by pre-acquisition paradoxical sleep deprivation (PSD), the effect of poisoning (0.15 M LiCl, 4% body weight) on the sleep--wakefulness pattern was studied in 12 rats with chronically implanted electrodes. The polygraphic recording showed that poisoning reduced the total sleep time in the subsequent 3 h from 57 to 42% and REM sleep from 6 to 2%. The lithium chloride effect was still more pronounced after 24-h REM sleep deprivation: the total sleep time decreased from 67 to 46% and REM sleep from 13 to 2%. The change of sleep--wakefulness pattern, most pronounced during the first hour of poisoning, gradually returned to normal but REM sleep was significantly reduced even 3 h after poisoning. It is concluded that 24-h PSD does not alleviate the subsequent poisoning. On the other hand, the lithium chloride induced reduction of post-acquisition REM sleep many enhance the learning impairment caused by pre-acquisition PSD."}
{"id": "PMID:209872", "title": "Intracellular horseradish peroxidase injection for correlation of light and electron microscopic anatomy with synaptic physiology of cultured mouse spinal cord neurons.", "content": "Synaptic interactions between spinal cord neurons grown in dissociated cell culture were studied electrophysiologically, and presynaptic cells were subsequently injected by intracellular iontophoresis with horseradish peroxidase (HRP). Following histochemical processing, injected cells were filled with dense reaction product which facilitated the light and electron microscopic identification of the individual physiologically typed neurons. This technique applied to neurons in monolayer culture allowed the visualization of complex intercellular relationships in essentially two dimensions. The number and distribution of morphologically defined synaptic contacts was determined for correlation with individual evoked postsynaptic potentials. HRP-filling of inhibitory and excitatory neurons revealed differences with respect to cellular geometry, axonal projection, and the number, location and ultrastructure of synaptic contacts.", "contents": "Intracellular horseradish peroxidase injection for correlation of light and electron microscopic anatomy with synaptic physiology of cultured mouse spinal cord neurons. Synaptic interactions between spinal cord neurons grown in dissociated cell culture were studied electrophysiologically, and presynaptic cells were subsequently injected by intracellular iontophoresis with horseradish peroxidase (HRP). Following histochemical processing, injected cells were filled with dense reaction product which facilitated the light and electron microscopic identification of the individual physiologically typed neurons. This technique applied to neurons in monolayer culture allowed the visualization of complex intercellular relationships in essentially two dimensions. The number and distribution of morphologically defined synaptic contacts was determined for correlation with individual evoked postsynaptic potentials. HRP-filling of inhibitory and excitatory neurons revealed differences with respect to cellular geometry, axonal projection, and the number, location and ultrastructure of synaptic contacts."}
{"id": "PMID:209876", "title": "Enzymatic and morphological properties of primary rat brain astrocyte cultures, and enzyme development in vivo.", "content": "The development of (Na+ + K+) ATPase, carbonic anhydrase and HCO3--stimulated ATPase activity was studied in developing rat brain in vivo, and in primary astrocyte cultures from 1--3-day-old rat brain as a function of increasing cell growth. The primary cultures showed an increase in all the above enzyme activities during cell growth, with time courses which were qualitatively similar to their development in vivo. Cell cultures grown separately from the cerebellum plus brain stem regions showed greater carbonic anhydrase activity than cerebral cultures over the entire 4-week growth period, corresponding to development of this activity in these same regions in vivo, HCO3-stimulated ATPase activity was slightly greater in cerebellar cultures and (Na+ + K+) ATPase activity was greater in cerebral cultures up to the second week of growth, resembling development of the same enzyme activities in vivo. C6 glioma and neuroblastoma cells showed no and 10-fold lower carbonic anhydrase activities respectively, compared to the primary astrocyte cultures. Addition of 1 mM N6-2'-O-dibutyryladenosine-3',5'-monophosphate (DBcAMP) in the presence of serum caused marked formation of cellular processes and increased carbonic anhydrase and (Na+ + K+) ATPase activity. Maximum effects were found 2 h after addition of 1 mM DBcAMP and thereafter declined. In the absence of serum such effects persisted for at least 24 h. Electron microscope studies showed large numbers of microtubule (approximately 20 nm diameter) and filamentous structures (less than or equal to 10 nm diameter) in the cytoplasm, which showed changes in distribution in cells treated with DBcAMP. This study suggests that the increase in ATPase and carbonic anhydrase activities in rat brain with increasing age may be in part a reflection of proliferation and development of astroglia cells. Together with the morphological data, it also provides additional evidence that primary cultures derived from neonatal rats may closely resemble developing astroglia in vivo.", "contents": "Enzymatic and morphological properties of primary rat brain astrocyte cultures, and enzyme development in vivo. The development of (Na+ + K+) ATPase, carbonic anhydrase and HCO3--stimulated ATPase activity was studied in developing rat brain in vivo, and in primary astrocyte cultures from 1--3-day-old rat brain as a function of increasing cell growth. The primary cultures showed an increase in all the above enzyme activities during cell growth, with time courses which were qualitatively similar to their development in vivo. Cell cultures grown separately from the cerebellum plus brain stem regions showed greater carbonic anhydrase activity than cerebral cultures over the entire 4-week growth period, corresponding to development of this activity in these same regions in vivo, HCO3-stimulated ATPase activity was slightly greater in cerebellar cultures and (Na+ + K+) ATPase activity was greater in cerebral cultures up to the second week of growth, resembling development of the same enzyme activities in vivo. C6 glioma and neuroblastoma cells showed no and 10-fold lower carbonic anhydrase activities respectively, compared to the primary astrocyte cultures. Addition of 1 mM N6-2'-O-dibutyryladenosine-3',5'-monophosphate (DBcAMP) in the presence of serum caused marked formation of cellular processes and increased carbonic anhydrase and (Na+ + K+) ATPase activity. Maximum effects were found 2 h after addition of 1 mM DBcAMP and thereafter declined. In the absence of serum such effects persisted for at least 24 h. Electron microscope studies showed large numbers of microtubule (approximately 20 nm diameter) and filamentous structures (less than or equal to 10 nm diameter) in the cytoplasm, which showed changes in distribution in cells treated with DBcAMP. This study suggests that the increase in ATPase and carbonic anhydrase activities in rat brain with increasing age may be in part a reflection of proliferation and development of astroglia cells. Together with the morphological data, it also provides additional evidence that primary cultures derived from neonatal rats may closely resemble developing astroglia in vivo."}
{"id": "PMID:209877", "title": "Prolidase activity in rat brain; developmental, regional and subcellular distribution.", "content": "We determined the regional and subcellular distribution of prolidase in rat brain and its changes with development. The most rapid changes in enzyme activity occurred perinatally, with a maximum level of activity 2 days before birth and a minimum 1 day after birth. Of the 7 regions examined, cerebellum had the highest enzyme level, followed by medulla. The lowest levels were found in the hypothalamus in the adult and in the midbrain in the young. Polidase was mainly soluble; over 55% was recovered in the S2fraction, and the rest was released from the particulate fractions by hypotonic shock. Brains of male rats contained a slightly higher level of the enzyme.", "contents": "Prolidase activity in rat brain; developmental, regional and subcellular distribution. We determined the regional and subcellular distribution of prolidase in rat brain and its changes with development. The most rapid changes in enzyme activity occurred perinatally, with a maximum level of activity 2 days before birth and a minimum 1 day after birth. Of the 7 regions examined, cerebellum had the highest enzyme level, followed by medulla. The lowest levels were found in the hypothalamus in the adult and in the midbrain in the young. Polidase was mainly soluble; over 55% was recovered in the S2fraction, and the rest was released from the particulate fractions by hypotonic shock. Brains of male rats contained a slightly higher level of the enzyme."}
{"id": "PMID:209878", "title": "Inhibition of enzyme induction in Pseudomonas aeruginosa by exogenous nucleotides.", "content": "Alkylsufatase induction in resting cell suspensions of P. aeruginosa was inhibited by exogenously supplied adenosine or by ATP (2mM). Adenine phosphate had no effect while AMP or ADP caused a slight stimulation of induction. The inhibitory effect of ATP required the presence of added Mg2+, was not reversed by cyclic-AMP (2mM), and was independent of the nature of the inducer. Of a number of other nucleoside triphosphates tested, only UTP (2mM) acted as an inhibitor of induction. These nucleotides at external concentrations of 6mM also inhibited alkysulfatase induction in actively growing cells.", "contents": "Inhibition of enzyme induction in Pseudomonas aeruginosa by exogenous nucleotides. Alkylsufatase induction in resting cell suspensions of P. aeruginosa was inhibited by exogenously supplied adenosine or by ATP (2mM). Adenine phosphate had no effect while AMP or ADP caused a slight stimulation of induction. The inhibitory effect of ATP required the presence of added Mg2+, was not reversed by cyclic-AMP (2mM), and was independent of the nature of the inducer. Of a number of other nucleoside triphosphates tested, only UTP (2mM) acted as an inhibitor of induction. These nucleotides at external concentrations of 6mM also inhibited alkysulfatase induction in actively growing cells."}
{"id": "PMID:209879", "title": "Congenital syndactyly: a reappraisal.", "content": "Digital syndactyly is a common congenital anomaly and is associated with other anomalies affecting the digits, the hand, the arm or even the entire body. In the past it has been considered a single entity. However, recent information provided by experimental embryology, studies of morphogenesis and other sources, suggests that there are at least two distinct entities: primary syndactyly due to interference with the sequence of events that normally culminate in the division of digits into discrete parts and secondary syndactyly due to readhesion of adjacent digits as a result of close contact between raw surfaces. Primary syndactylyl may arise de novo, or it may occur as a manifestation of a mutation phenomenon or as a genetically controlled syndrome. Secondary syndactyly is the result of mechanical adhesion of adjacent parts involved in a general reparative or healing process. The initial insult leading to amputation of a portion of the digits may or may not be genetically controlled; adhesion is fortuitous. Management of syndactyly is determined by the complexity of the malformation. For simple cutaneous syndactyly the surgeon should make a zigzag incision and provide a rectangular, proximally based flap for the floor of the web, usually before the child is 2 years of age. A full- or split-thickness skin graft should be applied to the defects. For complex deformities involving several digits and associated with postural or osseous malformation, several operative procedures may be required. The surgeon must be vigilant to note and correct the sequelae resulting from recurrent contractures and imbalances associated with growth.", "contents": "Congenital syndactyly: a reappraisal. Digital syndactyly is a common congenital anomaly and is associated with other anomalies affecting the digits, the hand, the arm or even the entire body. In the past it has been considered a single entity. However, recent information provided by experimental embryology, studies of morphogenesis and other sources, suggests that there are at least two distinct entities: primary syndactyly due to interference with the sequence of events that normally culminate in the division of digits into discrete parts and secondary syndactyly due to readhesion of adjacent digits as a result of close contact between raw surfaces. Primary syndactylyl may arise de novo, or it may occur as a manifestation of a mutation phenomenon or as a genetically controlled syndrome. Secondary syndactyly is the result of mechanical adhesion of adjacent parts involved in a general reparative or healing process. The initial insult leading to amputation of a portion of the digits may or may not be genetically controlled; adhesion is fortuitous. Management of syndactyly is determined by the complexity of the malformation. For simple cutaneous syndactyly the surgeon should make a zigzag incision and provide a rectangular, proximally based flap for the floor of the web, usually before the child is 2 years of age. A full- or split-thickness skin graft should be applied to the defects. For complex deformities involving several digits and associated with postural or osseous malformation, several operative procedures may be required. The surgeon must be vigilant to note and correct the sequelae resulting from recurrent contractures and imbalances associated with growth."}
{"id": "PMID:209881", "title": "Combination modality therapy in lung cancer: a survival study showing beneficial results of AMCOF (adriamycin, methotrexate, cyclophosphamide, oncovin and 5-fluorouracil).", "content": "Thirty-seven patients with advanced or recurrent lung cancer were randomized to cytoxan (CTX) alone, COMF (CTX, oncovin, methotrecate and 5-FU) or AMCOF (adriamycin, methotrexate, CTX, oncovin and 5-FU) after receiving radiation therapy to primary and bulky tumor sites. Median survival was 3 months for CTX, 6 months for COMF and 14 months for AMCOF. Analysis of those with cell (small cell) carcinoma showed median survival of 8.5 months. Oat cell cases treated with CTX survived 5 months (8 patients) with COMF 7.5 months (15 patients) and with AMCOF 13 months (14 patients). The median survival of those with adenocarcinoma or epidermoid carcinoma treated with CTX survived 3 months, with COMF 6 months and with AMCOF 15.5 months. Toxicity was moderate though no life-theatening toxicity developed in spite of the protocol design of escalation to achieve some degree of hematologic toxicity in all patients.", "contents": "Combination modality therapy in lung cancer: a survival study showing beneficial results of AMCOF (adriamycin, methotrexate, cyclophosphamide, oncovin and 5-fluorouracil). Thirty-seven patients with advanced or recurrent lung cancer were randomized to cytoxan (CTX) alone, COMF (CTX, oncovin, methotrecate and 5-FU) or AMCOF (adriamycin, methotrexate, CTX, oncovin and 5-FU) after receiving radiation therapy to primary and bulky tumor sites. Median survival was 3 months for CTX, 6 months for COMF and 14 months for AMCOF. Analysis of those with cell (small cell) carcinoma showed median survival of 8.5 months. Oat cell cases treated with CTX survived 5 months (8 patients) with COMF 7.5 months (15 patients) and with AMCOF 13 months (14 patients). The median survival of those with adenocarcinoma or epidermoid carcinoma treated with CTX survived 3 months, with COMF 6 months and with AMCOF 15.5 months. Toxicity was moderate though no life-theatening toxicity developed in spite of the protocol design of escalation to achieve some degree of hematologic toxicity in all patients."}
{"id": "PMID:209882", "title": "Intraaterial hepatic infusion and intravenous adriamycin for treatment of hepatocellular carcinoma: a clinical and pharmacology report.", "content": "Four patients received intraarterial (ia) hepatic infusion and 10 received intravenous (iv) adriamycin for hepatocellular carcinoma. Four of each group are evaluable. The remaining 6 patients died within 14 days of intravenous therapy and are, therefore, considered nonevaluable. Patients received 2 to 9 courses of adriamycin every 3 weeks. One half of each group of evaluable patients had partial responses (pr). The group had pr for 22.5 weeks (range 8 to 37). The iv group had pr 27.2 weeks (range: 16 to 38.5). Mean survival was 21 weeks for nonresponders, and 43 weeks for responders. Intraarterial infusion did not protect patients from adriamycin toxicity. Cardiac and liver toxicity were not seen, but marrow and gastrointestinal toxicity developed at 1.2 X 10(-7)M adriamycin serum level. Adriamycin disappearance curves after ia and iv therapy were similar for similar bilirubin levels, and prolonged with hyperbilirubinemia. Ascites fluid did not accumulate detectable adriamycin. Pharmacokinetics are described in this report.", "contents": "Intraaterial hepatic infusion and intravenous adriamycin for treatment of hepatocellular carcinoma: a clinical and pharmacology report. Four patients received intraarterial (ia) hepatic infusion and 10 received intravenous (iv) adriamycin for hepatocellular carcinoma. Four of each group are evaluable. The remaining 6 patients died within 14 days of intravenous therapy and are, therefore, considered nonevaluable. Patients received 2 to 9 courses of adriamycin every 3 weeks. One half of each group of evaluable patients had partial responses (pr). The group had pr for 22.5 weeks (range 8 to 37). The iv group had pr 27.2 weeks (range: 16 to 38.5). Mean survival was 21 weeks for nonresponders, and 43 weeks for responders. Intraarterial infusion did not protect patients from adriamycin toxicity. Cardiac and liver toxicity were not seen, but marrow and gastrointestinal toxicity developed at 1.2 X 10(-7)M adriamycin serum level. Adriamycin disappearance curves after ia and iv therapy were similar for similar bilirubin levels, and prolonged with hyperbilirubinemia. Ascites fluid did not accumulate detectable adriamycin. Pharmacokinetics are described in this report."}
{"id": "PMID:209883", "title": "The effect of estradiol-17-phenylpropionate and estradiol benzoate on N-nitrosomorpholine-induced liver carcinogenesis in ovariectomized female rats.", "content": "The influence of synthetic estrogens on the N-nitrosomorpholine (NNM)-induced liver carcinogenesis in ovariectomized young adult female rats was investigated and compared to rats which received only the carcinogen or estrogens. Estrogens when chronically administered after the cessation of carcinogen treatment increased the carcinogenic effect of NNM. In such conditioned animals the number of nodules per number of rats was 23/31, that of hepato-cellular carcinomas 9/31, whereas in animals which received only the hepato-carcinogen the incidence of nodules and carcinomas in liver was respectively 11/31 and 3/31. Higher incidence of benign and malignant tumors in other organs was also observed in these animals. Rats which received a single dose of estrogens simultaneously with NNM developed slightly fewer tumors in liver and in other organs. Since under my experimental conditions the long-term treatment with synthetic estrogens alone did not induce any focus, nodule or hepatocellular carcinoma in the liver. I suggest that the estrogens were acting rather as tumor promotors than true initiators of liver carcinogenesis.", "contents": "The effect of estradiol-17-phenylpropionate and estradiol benzoate on N-nitrosomorpholine-induced liver carcinogenesis in ovariectomized female rats. The influence of synthetic estrogens on the N-nitrosomorpholine (NNM)-induced liver carcinogenesis in ovariectomized young adult female rats was investigated and compared to rats which received only the carcinogen or estrogens. Estrogens when chronically administered after the cessation of carcinogen treatment increased the carcinogenic effect of NNM. In such conditioned animals the number of nodules per number of rats was 23/31, that of hepato-cellular carcinomas 9/31, whereas in animals which received only the hepato-carcinogen the incidence of nodules and carcinomas in liver was respectively 11/31 and 3/31. Higher incidence of benign and malignant tumors in other organs was also observed in these animals. Rats which received a single dose of estrogens simultaneously with NNM developed slightly fewer tumors in liver and in other organs. Since under my experimental conditions the long-term treatment with synthetic estrogens alone did not induce any focus, nodule or hepatocellular carcinoma in the liver. I suggest that the estrogens were acting rather as tumor promotors than true initiators of liver carcinogenesis."}
{"id": "PMID:209884", "title": "Mucinous carcinoma of anal duct origin presenting clinically as a vaginal cyst.", "content": "The vast majority of vaginal submucosal cysts are benign lesions. Primary malignant tumors of the vagina are infrequent and most are mucosal lesions. A case is described in which an unusual neoplasm, anal duct carcinoma, presented clinically as a vaginal lesion. The importance of considering anal neoplasia in the differential diagnosis of cystic vaginal lesions is noted.", "contents": "Mucinous carcinoma of anal duct origin presenting clinically as a vaginal cyst. The vast majority of vaginal submucosal cysts are benign lesions. Primary malignant tumors of the vagina are infrequent and most are mucosal lesions. A case is described in which an unusual neoplasm, anal duct carcinoma, presented clinically as a vaginal lesion. The importance of considering anal neoplasia in the differential diagnosis of cystic vaginal lesions is noted."}
{"id": "PMID:209885", "title": "Histiocytic tumors of the larynx: a clinicopathological study with review of the literature.", "content": "A case of primary malignant fibrous histiocytoma of the larynx occurring in a 58-year-old man is described. This neoplasm is extremely rare in the larynx and the case reported (the second described by me) is the fifth so far reported in the world literature. The patient died after 19 months from first surgical treatment and the autopsy confirmed the histological diagnosis. The cases of histiocytic tumors of the larynx previously reported in the literature are re-examined and reclassified. Biological behavior and the therapy of the tumor, as well as differential diagnosis from other neoplasms, are discussed.", "contents": "Histiocytic tumors of the larynx: a clinicopathological study with review of the literature. A case of primary malignant fibrous histiocytoma of the larynx occurring in a 58-year-old man is described. This neoplasm is extremely rare in the larynx and the case reported (the second described by me) is the fifth so far reported in the world literature. The patient died after 19 months from first surgical treatment and the autopsy confirmed the histological diagnosis. The cases of histiocytic tumors of the larynx previously reported in the literature are re-examined and reclassified. Biological behavior and the therapy of the tumor, as well as differential diagnosis from other neoplasms, are discussed."}
{"id": "PMID:209886", "title": "Malignant fibrous histiocytoma (malignant fibrous xanthoma: xanthosarcoma) of bone.", "content": "Seven cases of malignant fibrous histiocytoma of bone are documented. In addition to typical histologic features such as the presence of a storiform pattern, histiocytic and fibrocytic cell types and severe cellular atypism, in five cases there were areas in which osteoclast-type giant cells were prominent and the lesion resembled a giant cell tumor. Three of the seven patients developed pulmonary metastases within two years of amputation, one developed extensive local recurrence including soft tissue and vascular invasion, and the other three are without evidence of disease but have been followed for only short periods.", "contents": "Malignant fibrous histiocytoma (malignant fibrous xanthoma: xanthosarcoma) of bone. Seven cases of malignant fibrous histiocytoma of bone are documented. In addition to typical histologic features such as the presence of a storiform pattern, histiocytic and fibrocytic cell types and severe cellular atypism, in five cases there were areas in which osteoclast-type giant cells were prominent and the lesion resembled a giant cell tumor. Three of the seven patients developed pulmonary metastases within two years of amputation, one developed extensive local recurrence including soft tissue and vascular invasion, and the other three are without evidence of disease but have been followed for only short periods."}
{"id": "PMID:209887", "title": "Lobular neoplasia (so-called lobular carcinoma in situ) of the breast.", "content": "In a review and reclassification of 5,560 benign epithelial lesions of the breast entered in the files of the Laboratory of Surgical Pathology at Columbia, we found 211 examples of the type of lobular proliferation occurring alone without co-existing infiltrating carcinoma, which we prefer to call lobular neoplasia, but which is generally referred to as noninfiltrating lobular carcinoma in situ. We regard this lesion as a separate distinctive pathological-clinical entity. These 211 cases are studied from a number of parameters, including the ages of the patients, the breast affected, the length of the follow-up, the interval between the initial diagnosis and the frank carcinoma which eventually developed in 17.1 percent of the patients. The relationship of microscopic qualitative and quantitative variations in the lobular neoplasia to subsequent carcinoma was studied; the variations were not found to have any value in predicting subsequent carcinoma. This study is unique in that we have data as to the frequency of a family history of carcinoma in a mother or sister, and also as to the occurrence of gross cystic disease in our patients with lobular neoplasia. We have determined the ratio between the observed and expected numbers of patients developing carcinoma in the several possible combinations of these three factors which predispose to carcinoma. We report that the predisposition is cumulative: in patients in whom all three predisposing factors were present the ratio of observed to expected risk of carcinoma was 13:8. We do not recommend mastectomy for lobular neoplasia, but only systematic follow-up by palpation of the patients' breasts every four months.", "contents": "Lobular neoplasia (so-called lobular carcinoma in situ) of the breast. In a review and reclassification of 5,560 benign epithelial lesions of the breast entered in the files of the Laboratory of Surgical Pathology at Columbia, we found 211 examples of the type of lobular proliferation occurring alone without co-existing infiltrating carcinoma, which we prefer to call lobular neoplasia, but which is generally referred to as noninfiltrating lobular carcinoma in situ. We regard this lesion as a separate distinctive pathological-clinical entity. These 211 cases are studied from a number of parameters, including the ages of the patients, the breast affected, the length of the follow-up, the interval between the initial diagnosis and the frank carcinoma which eventually developed in 17.1 percent of the patients. The relationship of microscopic qualitative and quantitative variations in the lobular neoplasia to subsequent carcinoma was studied; the variations were not found to have any value in predicting subsequent carcinoma. This study is unique in that we have data as to the frequency of a family history of carcinoma in a mother or sister, and also as to the occurrence of gross cystic disease in our patients with lobular neoplasia. We have determined the ratio between the observed and expected numbers of patients developing carcinoma in the several possible combinations of these three factors which predispose to carcinoma. We report that the predisposition is cumulative: in patients in whom all three predisposing factors were present the ratio of observed to expected risk of carcinoma was 13:8. We do not recommend mastectomy for lobular neoplasia, but only systematic follow-up by palpation of the patients' breasts every four months."}
{"id": "PMID:209888", "title": "Appearance of intestinal type of tumor cells in hepatoma tissue induced by 3'-methyl-4-dimethylaminoazobenzene.", "content": "Carcinoma tissues induced by 3'-methyl-4-dimethylaminoazobenzene were investigated both morphologically and biochemically. The most prominent histological pattern was an undifferentiated carcinomatous one. While this type of carcinoma, histologically, appeared to be due to a uniform population of cells, electron microscopic examination revealed that the carcinoma tissue was composed of many types of cells including cells that contained either the brush border or the mucous droplets seen in goblet cells. In addition, tumor cells that contain serotonin-like granules were noticed. An electrophoretogram of alkaline phosphatase in the tissue extract of this type of carcinoma revealed distinctly the presence of its intestinal isozyme. These findings evidently show that carcinoma induced by 3'-methyl-4-dimethylaminoazobenzene includes in addition to the cells differentiated toward hepatocytes or cholangiolar cells, those differentiated toward intestinal epithelial cells.", "contents": "Appearance of intestinal type of tumor cells in hepatoma tissue induced by 3'-methyl-4-dimethylaminoazobenzene. Carcinoma tissues induced by 3'-methyl-4-dimethylaminoazobenzene were investigated both morphologically and biochemically. The most prominent histological pattern was an undifferentiated carcinomatous one. While this type of carcinoma, histologically, appeared to be due to a uniform population of cells, electron microscopic examination revealed that the carcinoma tissue was composed of many types of cells including cells that contained either the brush border or the mucous droplets seen in goblet cells. In addition, tumor cells that contain serotonin-like granules were noticed. An electrophoretogram of alkaline phosphatase in the tissue extract of this type of carcinoma revealed distinctly the presence of its intestinal isozyme. These findings evidently show that carcinoma induced by 3'-methyl-4-dimethylaminoazobenzene includes in addition to the cells differentiated toward hepatocytes or cholangiolar cells, those differentiated toward intestinal epithelial cells."}
{"id": "PMID:209889", "title": "Lysosomal enzymes in macrophages of colonic tumors induced in rats by 1,2-dimethylhydrazine dihydrochloride.", "content": "Ten weekly doses of dimethylhydrazine (30 mg/kg) were given to rats to induce colonic tumors. Histochemical and electron cytochemical studies revealed a distinct pattern of lysosomal acid phosphatase and beta-glucuronidase activity in macrophages in the stroma of these neoplasms. A dramatic increase in the number of acid phosphatase-rich macrophages was present in adenomas when compared to that in normal colonic mucosa. Fewer numbers of these cells were seen in well-differentiated adenocarcinomas, and they were barely detectable in highly invasive mucinous adenocarcinomas. It is postulated that these macrophages may play a role in preventing the invasion of adenomatous neoplasms into the submucosa. Application of histochemical techniques to study macrophage lysosomal enzymes may prove a useful diagnostic tool in differentiation of human colonic tumors for prognostic evaluation.", "contents": "Lysosomal enzymes in macrophages of colonic tumors induced in rats by 1,2-dimethylhydrazine dihydrochloride. Ten weekly doses of dimethylhydrazine (30 mg/kg) were given to rats to induce colonic tumors. Histochemical and electron cytochemical studies revealed a distinct pattern of lysosomal acid phosphatase and beta-glucuronidase activity in macrophages in the stroma of these neoplasms. A dramatic increase in the number of acid phosphatase-rich macrophages was present in adenomas when compared to that in normal colonic mucosa. Fewer numbers of these cells were seen in well-differentiated adenocarcinomas, and they were barely detectable in highly invasive mucinous adenocarcinomas. It is postulated that these macrophages may play a role in preventing the invasion of adenomatous neoplasms into the submucosa. Application of histochemical techniques to study macrophage lysosomal enzymes may prove a useful diagnostic tool in differentiation of human colonic tumors for prognostic evaluation."}
{"id": "PMID:209891", "title": "Aggregation of platelets and cell membrane vesiculation by rat cells transformed in vitro by Rous sarcoma virus.", "content": "Primary rat embryo cells and established normal rat kidney cells transformed in vitro by Rous sarcoma virus induced the aggregation of rat platelets in vitro. The aggregating activity was shown to be specific for the transformed cells and was absent in the normal parent cells. The aggregation reaction is accompanied by the release of serotonin from the platelets. Further analysis and purification of this activity from the transformed cells demonstrated that the activity is shed from the cells growing in culture and is associated with membrane vesicles of heterogenous size. The normal cells also produced vesicles in culture; however, the level of vesicle productio was less than that from transformed cells, and the platelet aggregation and serotonin release activities were greatly reduced or absent in these vesicles.", "contents": "Aggregation of platelets and cell membrane vesiculation by rat cells transformed in vitro by Rous sarcoma virus. Primary rat embryo cells and established normal rat kidney cells transformed in vitro by Rous sarcoma virus induced the aggregation of rat platelets in vitro. The aggregating activity was shown to be specific for the transformed cells and was absent in the normal parent cells. The aggregation reaction is accompanied by the release of serotonin from the platelets. Further analysis and purification of this activity from the transformed cells demonstrated that the activity is shed from the cells growing in culture and is associated with membrane vesicles of heterogenous size. The normal cells also produced vesicles in culture; however, the level of vesicle productio was less than that from transformed cells, and the platelet aggregation and serotonin release activities were greatly reduced or absent in these vesicles."}
{"id": "PMID:209892", "title": "In vitro effects of lipoprotein-associated cytotoxic factor on rat prostate adenocarcinoma cells.", "content": "As assayed by the colony inhibition technique, sera from rats at an advanced stage of pregnancy were cytotoxic to a number of tumorigenic and \"nontransformed\" cell lines. The cytotoxic effect is not species specific. Primary fetal rat kidney cells were not susceptible to this cytotoxic effect. The level of demonstrable cytotoxicity in sera rose gradually as gestation advanced; it peaked at 48 hr before parturition and disappeared thereafter. Sera from control nonpregnant rats were not cytotoxic. The cytotoxic factor(s) in sera was demonstrable only in the very low-density lipoprotein (VLDL) (hydrated density less than 1.006 g/ml) fraction. Reconstitution studies suggest that: (a) inhibitors which usually mask the cytotoxic actitivity of VLDL in whole serum, are present; and (b) pregnancy initiates enhanced VLDL synthesis, which exceeds the masking effect. The possible role of this cytotoxic VLDL in host defense against neoplasia is discussed.", "contents": "In vitro effects of lipoprotein-associated cytotoxic factor on rat prostate adenocarcinoma cells. As assayed by the colony inhibition technique, sera from rats at an advanced stage of pregnancy were cytotoxic to a number of tumorigenic and \"nontransformed\" cell lines. The cytotoxic effect is not species specific. Primary fetal rat kidney cells were not susceptible to this cytotoxic effect. The level of demonstrable cytotoxicity in sera rose gradually as gestation advanced; it peaked at 48 hr before parturition and disappeared thereafter. Sera from control nonpregnant rats were not cytotoxic. The cytotoxic factor(s) in sera was demonstrable only in the very low-density lipoprotein (VLDL) (hydrated density less than 1.006 g/ml) fraction. Reconstitution studies suggest that: (a) inhibitors which usually mask the cytotoxic actitivity of VLDL in whole serum, are present; and (b) pregnancy initiates enhanced VLDL synthesis, which exceeds the masking effect. The possible role of this cytotoxic VLDL in host defense against neoplasia is discussed."}
{"id": "PMID:209893", "title": "Effect of phorbol myristate acetate on cyclic nucleotide levels in mouse epidermis.", "content": "Basal levels of cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monophosphate were determined in mouse epidermis in vivo after a single topical treatment with the tumor promoter phorbol myristate acetate. No changes in cyclic adenosine 3':5'-monophosphate levels were found from 0 to 72 hr after treatment. A twofold increase in cyclic guanosine 3':5'-monophosphate was found 36 hr after treatment. This increase had subsided by 72 hr. The effect of phorbol myristate acetate on DNA, RNA, and protein synthesis in the epidermis of Ha/ICR mice was also measured.", "contents": "Effect of phorbol myristate acetate on cyclic nucleotide levels in mouse epidermis. Basal levels of cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monophosphate were determined in mouse epidermis in vivo after a single topical treatment with the tumor promoter phorbol myristate acetate. No changes in cyclic adenosine 3':5'-monophosphate levels were found from 0 to 72 hr after treatment. A twofold increase in cyclic guanosine 3':5'-monophosphate was found 36 hr after treatment. This increase had subsided by 72 hr. The effect of phorbol myristate acetate on DNA, RNA, and protein synthesis in the epidermis of Ha/ICR mice was also measured."}
{"id": "PMID:209894", "title": "Cultural, morphological, cell membrane, enzymatic, and neoplastic properties of cell lines derived from a Hodgkin's disease lymph node.", "content": "A neoplastic cell line (designated HuT11) has been established in continuous culture from an involved lymph node of a patient with Stage IIA Hodgkin's disease of the mixed cellularity type. The HuT11 line has been morphologically heterogeneous, consisting of mononucleate lymphoid-like cells, polygonal epithelioid cells, and mono-, bi-, and multinucleate giant cells. Four clones initiated from isolated binucleate giant cells of the HuT11 line also have been successfully established as continuous cell lines. The cloned lines have been morphologically distinct and more homogeneous, although typical giant cells have consistently appeared throughout the long-term culture of each. The HuT11 lines have grown as monolayers in McCoy's Medium 5A supplemented with 10% fetal calf serum, with generation times of 12 to 14 hr and high saturation densities. Cytogenetic studies showed that early and later passages of HuT11 cells were aneuploid, and all cell lines were successfully heterotransplanted in the hamster cheek pouch. Repeated indirect immunofluorescence examinations have shown each cell line to be negative for Epstein-Barr virus nuclear antigen. Indirect immunofluorescence tests in which monospecific immunoglobulins were used revealed positive membrane reactions for the gamma (heavy)-chain and kappa (light)-chain of human immunoglobulin G in approximately 20% of viable cells in each line; however, direct immunofluorescence with anti-human immunoglobulin G F(ab')2 reagent failed to confirm these reactions. Rosette tests for B- and T-lymphocyte and macrophage membrane receptors yielded negative results. All cell lines were strongly phagocytic for latex particles and neutral red dye. Cytochemical stains of the monolayers revealed abundant esterase, fluoride-resistant nonspecific esterase, acid phosphatase, and leucine aminopeptidase activities, while lysozyme assays were negative. Although some properties of the HuT11 lines have suggested a macrophage derivation, an undifferentiated lymphoid cell origin of the Hodgkin's neoplastic cell remains a possibility.", "contents": "Cultural, morphological, cell membrane, enzymatic, and neoplastic properties of cell lines derived from a Hodgkin's disease lymph node. A neoplastic cell line (designated HuT11) has been established in continuous culture from an involved lymph node of a patient with Stage IIA Hodgkin's disease of the mixed cellularity type. The HuT11 line has been morphologically heterogeneous, consisting of mononucleate lymphoid-like cells, polygonal epithelioid cells, and mono-, bi-, and multinucleate giant cells. Four clones initiated from isolated binucleate giant cells of the HuT11 line also have been successfully established as continuous cell lines. The cloned lines have been morphologically distinct and more homogeneous, although typical giant cells have consistently appeared throughout the long-term culture of each. The HuT11 lines have grown as monolayers in McCoy's Medium 5A supplemented with 10% fetal calf serum, with generation times of 12 to 14 hr and high saturation densities. Cytogenetic studies showed that early and later passages of HuT11 cells were aneuploid, and all cell lines were successfully heterotransplanted in the hamster cheek pouch. Repeated indirect immunofluorescence examinations have shown each cell line to be negative for Epstein-Barr virus nuclear antigen. Indirect immunofluorescence tests in which monospecific immunoglobulins were used revealed positive membrane reactions for the gamma (heavy)-chain and kappa (light)-chain of human immunoglobulin G in approximately 20% of viable cells in each line; however, direct immunofluorescence with anti-human immunoglobulin G F(ab')2 reagent failed to confirm these reactions. Rosette tests for B- and T-lymphocyte and macrophage membrane receptors yielded negative results. All cell lines were strongly phagocytic for latex particles and neutral red dye. Cytochemical stains of the monolayers revealed abundant esterase, fluoride-resistant nonspecific esterase, acid phosphatase, and leucine aminopeptidase activities, while lysozyme assays were negative. Although some properties of the HuT11 lines have suggested a macrophage derivation, an undifferentiated lymphoid cell origin of the Hodgkin's neoplastic cell remains a possibility."}
{"id": "PMID:209897", "title": "Particles resembling C-type oncornaviruses in normal rat prostate.", "content": "A large number of particles resembling oncornaviruses were observed in the ventral lobe of a normal rat prostate. The particles were seen budding into the intercellular spaces of the epithelial lumen cells. They exhibited features morphologically similar to immature C-type particles, with an electron-lucent center and a diameter of approximately 100 nm. Neither intracellular A-type particles nor mature C-type particles were observed. This is the first report of particles resembling oncornaviruses in normal rat prostatic tissue.", "contents": "Particles resembling C-type oncornaviruses in normal rat prostate. A large number of particles resembling oncornaviruses were observed in the ventral lobe of a normal rat prostate. The particles were seen budding into the intercellular spaces of the epithelial lumen cells. They exhibited features morphologically similar to immature C-type particles, with an electron-lucent center and a diameter of approximately 100 nm. Neither intracellular A-type particles nor mature C-type particles were observed. This is the first report of particles resembling oncornaviruses in normal rat prostatic tissue."}
{"id": "PMID:209899", "title": "Effect of submaximal isometric exercise on catecholamine, cAMP and lactate concentrations in the coronary circulation of man, following atropine and oxprenolol.", "content": "The effects of atropine and oxprenolol on changes occurring in total catecholamine, cyclic AMP (cAMP) and lactate concentrations in arterial and coronary sinus blood, during submaximal isometric exercise, were studied in 10 patients. Static one-third-maximal handgrip exercise, sustained for 5 minutes, did not produce an increase in either arterial or coronary sinus plasma catecholamine concentrations (measured at rest and during the last minute of exercise) and was not influenced by atropine and oxprenolol. Myocardial lactate production did not occur. Coronary sinus cAMP concentrations fell during isometric exercise from 11.53 +- 0.93 to 9.42 +/- 0.81 nmol/l (+/ SEM), and following autonomic blockade from 12.46 +/- 1.12 TO 9.6 +/- 0.87 nmol/l but rose on subsequent isometric exercise to 11.27 +/- 0.8 nmol/l (p less than 0.05). Although this latter increase could still be due to beta-adrenergic stimulation, the absence of any change in catecholamine concentrations in the presence of beta-blockade suggests that other factors may have been responsible.", "contents": "Effect of submaximal isometric exercise on catecholamine, cAMP and lactate concentrations in the coronary circulation of man, following atropine and oxprenolol. The effects of atropine and oxprenolol on changes occurring in total catecholamine, cyclic AMP (cAMP) and lactate concentrations in arterial and coronary sinus blood, during submaximal isometric exercise, were studied in 10 patients. Static one-third-maximal handgrip exercise, sustained for 5 minutes, did not produce an increase in either arterial or coronary sinus plasma catecholamine concentrations (measured at rest and during the last minute of exercise) and was not influenced by atropine and oxprenolol. Myocardial lactate production did not occur. Coronary sinus cAMP concentrations fell during isometric exercise from 11.53 +- 0.93 to 9.42 +/- 0.81 nmol/l (+/ SEM), and following autonomic blockade from 12.46 +/- 1.12 TO 9.6 +/- 0.87 nmol/l but rose on subsequent isometric exercise to 11.27 +/- 0.8 nmol/l (p less than 0.05). Although this latter increase could still be due to beta-adrenergic stimulation, the absence of any change in catecholamine concentrations in the presence of beta-blockade suggests that other factors may have been responsible."}
{"id": "PMID:209900", "title": "Effects of ACTH and 3',5'-cyclic purine nucleotides on the morphology and metabolism of normal adult human adrenocortical cells in primary tissue culture.", "content": "Stereological studies showed that treatment of normal adult human adrenocortical cells in primary culture with ACTH or cyclic-AMP for 2 days results in similar increases in the volume of cells, of the mitochondrial and \"membrane space\" compartments and of the surface area of the smooth endoplasmic reticulum and mitochondrial cristae, and decrease in the lipid content of the cells. These changes were more marked after 8 days of treatment. Treatment for 2 days with cyclic-GMP had no striking effects on cell ultrastructure, whereas an 8-day treatment led to ultrastructural changes similar to those obtained after 2 days of ACTH- or cyclic-AMP-treatment. A discrete population of untreated cortical cells maintained a slow proliferation that was not effected by exposure to cyclic-GMP, but was significantly increased in cultures treated with ACTH or cyclic-AMP. Radioimmunological studies showed that untreated cortical cells kept secreting progesterone and cortisol and that ACTH, but neither cyclic nucleotide, increased the secretion rate per cell of both hormones. These results assign a major role to cyclic-AMP and a minor one to cyclic-GMP in the mediation of the differentiation-promoting and trophic effects, but not in the steroidogenic effects of ACTH on the human adrenal cortex.", "contents": "Effects of ACTH and 3',5'-cyclic purine nucleotides on the morphology and metabolism of normal adult human adrenocortical cells in primary tissue culture. Stereological studies showed that treatment of normal adult human adrenocortical cells in primary culture with ACTH or cyclic-AMP for 2 days results in similar increases in the volume of cells, of the mitochondrial and \"membrane space\" compartments and of the surface area of the smooth endoplasmic reticulum and mitochondrial cristae, and decrease in the lipid content of the cells. These changes were more marked after 8 days of treatment. Treatment for 2 days with cyclic-GMP had no striking effects on cell ultrastructure, whereas an 8-day treatment led to ultrastructural changes similar to those obtained after 2 days of ACTH- or cyclic-AMP-treatment. A discrete population of untreated cortical cells maintained a slow proliferation that was not effected by exposure to cyclic-GMP, but was significantly increased in cultures treated with ACTH or cyclic-AMP. Radioimmunological studies showed that untreated cortical cells kept secreting progesterone and cortisol and that ACTH, but neither cyclic nucleotide, increased the secretion rate per cell of both hormones. These results assign a major role to cyclic-AMP and a minor one to cyclic-GMP in the mediation of the differentiation-promoting and trophic effects, but not in the steroidogenic effects of ACTH on the human adrenal cortex."}
{"id": "PMID:209904", "title": "Pesticide-induced changes in hepatic microsomal enzyme systems: further studies on the effects of 1,1,-di(p-chlorophenyl)-2-chloroethylene (DDMU) in the Japanese quail.", "content": "Changes in the liver resulting from the low level dietary administration of 1,1-di(p-chlorophenyl)-2-chloroethylene (DDMU),p,p'-DDT, o,p'-DDT, p,p'-DDD and p,p'-DDE to Japanese Quail have been monitored. DDMU was exceptional in causing substantial increases in relative liver wt. and hepatic glucose-6-phosphatase after feeding at 100 ppm for 28 days. The time course of liver enzyme induction by DDMU has also been studied in Japanese Quail after periods of dietary administration ranging from 1--28 days with particular reference to changes in hepatic cytochrome P-450 and relative liver wt. Structural changes in the liver have been followed by reference to protein and lipid components. The hepatic response to DDMU appears to be biphasic. Initially there are substantial increases in hepatic cytochrome P-450 and relative liver wt., but the latter is largely due to accumulation of triglycerides. After approximately 20 days the level of hepatic cytochrome P-450 remain at a high 'plateau' level. This secondary phase of liver induction probably involves cell proliferation. It is concluded that DDMU causes major changes in the avian liver and either directly or through a metabolite causes pronounced microsomal enzyme induction.", "contents": "Pesticide-induced changes in hepatic microsomal enzyme systems: further studies on the effects of 1,1,-di(p-chlorophenyl)-2-chloroethylene (DDMU) in the Japanese quail. Changes in the liver resulting from the low level dietary administration of 1,1-di(p-chlorophenyl)-2-chloroethylene (DDMU),p,p'-DDT, o,p'-DDT, p,p'-DDD and p,p'-DDE to Japanese Quail have been monitored. DDMU was exceptional in causing substantial increases in relative liver wt. and hepatic glucose-6-phosphatase after feeding at 100 ppm for 28 days. The time course of liver enzyme induction by DDMU has also been studied in Japanese Quail after periods of dietary administration ranging from 1--28 days with particular reference to changes in hepatic cytochrome P-450 and relative liver wt. Structural changes in the liver have been followed by reference to protein and lipid components. The hepatic response to DDMU appears to be biphasic. Initially there are substantial increases in hepatic cytochrome P-450 and relative liver wt., but the latter is largely due to accumulation of triglycerides. After approximately 20 days the level of hepatic cytochrome P-450 remain at a high 'plateau' level. This secondary phase of liver induction probably involves cell proliferation. It is concluded that DDMU causes major changes in the avian liver and either directly or through a metabolite causes pronounced microsomal enzyme induction."}
{"id": "PMID:209905", "title": "[Agenesis of the femoral vein in the framework of vascular dysplasias of the lower limbs. Clinical case].", "content": "Venous dilatations of the lower limbs, especially if associated with others abnormalities, may reflect pathogenetic mechanisms far more complex and diverse than plain insufficiency of the sephena, all the way to congenital vascular anomalies of all possible types and still dubious classification. In such conditions a prerequisite of prime importance is the complete exploration of the whole arterial and venous vasculature of the limb, first of all in order to avoid rash therapeutic decisions, and then to help clarify the diagnosis and select the most appropriate treatment from among the numerous technics available.", "contents": "[Agenesis of the femoral vein in the framework of vascular dysplasias of the lower limbs. Clinical case]. Venous dilatations of the lower limbs, especially if associated with others abnormalities, may reflect pathogenetic mechanisms far more complex and diverse than plain insufficiency of the sephena, all the way to congenital vascular anomalies of all possible types and still dubious classification. In such conditions a prerequisite of prime importance is the complete exploration of the whole arterial and venous vasculature of the limb, first of all in order to avoid rash therapeutic decisions, and then to help clarify the diagnosis and select the most appropriate treatment from among the numerous technics available."}
{"id": "PMID:209906", "title": "Glucose-6-phosphatase activity in liver and blood platelets of two patients with glycogen storage disease type I.", "content": "Glucose-6-phosphatase (G-6-Pase) activity in liver and blood platelets of two patients with glycogen storage disease (GSD) type I is described. Both patients had a reduced activity of G-6-Pase in liver. The km value for glucose 6-phosphate (G-6-P) of residual activity in liver of both patients was similar to that of control liver. We could not demonstrate any reduced activity of platelet G-6-Pase in the patients. Platelet G-6-Pase with our assay method seems to represent a nonspecific phosphatase activity. Our observation suggests that it is necessary to examine platelet G-6-Pase of many other patients with GSD type I to confirm that G-6-Pase deficiency can be diagnosed by enzyme assay performed on blood platelets.", "contents": "Glucose-6-phosphatase activity in liver and blood platelets of two patients with glycogen storage disease type I. Glucose-6-phosphatase (G-6-Pase) activity in liver and blood platelets of two patients with glycogen storage disease (GSD) type I is described. Both patients had a reduced activity of G-6-Pase in liver. The km value for glucose 6-phosphate (G-6-P) of residual activity in liver of both patients was similar to that of control liver. We could not demonstrate any reduced activity of platelet G-6-Pase in the patients. Platelet G-6-Pase with our assay method seems to represent a nonspecific phosphatase activity. Our observation suggests that it is necessary to examine platelet G-6-Pase of many other patients with GSD type I to confirm that G-6-Pase deficiency can be diagnosed by enzyme assay performed on blood platelets."}
{"id": "PMID:209907", "title": "Triglyceride lipase activity in postheparin plasma and plasma lipoproteins in liver disease.", "content": "Hepatic lipase activity and lipoprotein lipase activity were studied in postheparin plasma from 14 patients with various liver disorders. Plasma lecithin: cholesterol acyltransferase (LCAT) activity and lipoprotein composition and structure were also estimated. Five patients had lower hepatic lipase activity than the lowest control value, and in three of these no hepatic lipase activity was detected. Lipoprotein lipase was low in 5 patients, but in only one of them was hepatic lipase activity also low. Hepatic lipase was not significantly correlated to the concentration of plasma triglycerides, either in controls or in patients, whereas lipoprotein lipase was negatively correlated with plasma triglycerides both in controls and patients. Lipoprotein lipase and LCAT activity, but not hepatic lipase, was negatively correlated to the triglyceride content of the low density lipoproteins (density 1.019-1.063 g/ml) from the patients. No specific lipid or lipoprotein pattern was found in plasma from the patients with a low or without any hepatic lipase activity. The results suggest an important role of lipoprotein lipase and LCAT, for the increased content of triglycerides in the low density lipoproteins in patients with liver disease. The role of hepatic lipase remains unclear.", "contents": "Triglyceride lipase activity in postheparin plasma and plasma lipoproteins in liver disease. Hepatic lipase activity and lipoprotein lipase activity were studied in postheparin plasma from 14 patients with various liver disorders. Plasma lecithin: cholesterol acyltransferase (LCAT) activity and lipoprotein composition and structure were also estimated. Five patients had lower hepatic lipase activity than the lowest control value, and in three of these no hepatic lipase activity was detected. Lipoprotein lipase was low in 5 patients, but in only one of them was hepatic lipase activity also low. Hepatic lipase was not significantly correlated to the concentration of plasma triglycerides, either in controls or in patients, whereas lipoprotein lipase was negatively correlated with plasma triglycerides both in controls and patients. Lipoprotein lipase and LCAT activity, but not hepatic lipase, was negatively correlated to the triglyceride content of the low density lipoproteins (density 1.019-1.063 g/ml) from the patients. No specific lipid or lipoprotein pattern was found in plasma from the patients with a low or without any hepatic lipase activity. The results suggest an important role of lipoprotein lipase and LCAT, for the increased content of triglycerides in the low density lipoproteins in patients with liver disease. The role of hepatic lipase remains unclear."}
{"id": "PMID:209908", "title": "An evaluation of quantitative agarose-gel electrophoresis of serum lipoproteins.", "content": "The method of Hatch et al. (Hatch, F.T., Lindgren, F.T., Adamson, G.L., Jensen, L.C. and Wong, A.W. (1973) J. Lab. Clin. Med. 81, 946-960) of quantitative determination of serum lipoproteins has been compared with preparative ultracentrifugation and chemical analysis of the lipoprotein fractions and a good concordance was demonstrated. The replacement of the coefficients proposed by Hatch et al. by the ones derived from the present study does not bring about relevant changes of the results when the harmonic mean of two calibration factors, derived from serum cholesterol and triglycerides, is used, thus indicating that this method of calculation minimizes the effect of variation of the chemical composition of lipoproteins. The method is sufficiently reliable and reproducible for practical pruposes and is recommended as the standard method for the clinical laboratory.", "contents": "An evaluation of quantitative agarose-gel electrophoresis of serum lipoproteins. The method of Hatch et al. (Hatch, F.T., Lindgren, F.T., Adamson, G.L., Jensen, L.C. and Wong, A.W. (1973) J. Lab. Clin. Med. 81, 946-960) of quantitative determination of serum lipoproteins has been compared with preparative ultracentrifugation and chemical analysis of the lipoprotein fractions and a good concordance was demonstrated. The replacement of the coefficients proposed by Hatch et al. by the ones derived from the present study does not bring about relevant changes of the results when the harmonic mean of two calibration factors, derived from serum cholesterol and triglycerides, is used, thus indicating that this method of calculation minimizes the effect of variation of the chemical composition of lipoproteins. The method is sufficiently reliable and reproducible for practical pruposes and is recommended as the standard method for the clinical laboratory."}
{"id": "PMID:209910", "title": "The quantitative determination of apolipoprotein A-I (apo-lp-Gln I) in human serum by radial immunodiffusion assay (RID).", "content": "A radial immunodiffusion (RID) assay was developed to determine the concentration of the major apolipoprotein (apolipoprotein A-I, apo-lp-Gln I) of human high density lipoproteins (HDL): (1) In a random population sample of apparently healthy persons (104 women, 95 men) aged 40-49 years, serum levels of apo A-I were determined. For both women and men a value of 137 +/- 23 mg/dl was found. (2) Values of 139 +/- 21 mg/dl were found in a group of 31 women taking oral contraceptives, i.e. an insignificant increase in apo A-I level. (3) In two volunteers, apo A-I levels showed no significant variation in a 24-h period.", "contents": "The quantitative determination of apolipoprotein A-I (apo-lp-Gln I) in human serum by radial immunodiffusion assay (RID). A radial immunodiffusion (RID) assay was developed to determine the concentration of the major apolipoprotein (apolipoprotein A-I, apo-lp-Gln I) of human high density lipoproteins (HDL): (1) In a random population sample of apparently healthy persons (104 women, 95 men) aged 40-49 years, serum levels of apo A-I were determined. For both women and men a value of 137 +/- 23 mg/dl was found. (2) Values of 139 +/- 21 mg/dl were found in a group of 31 women taking oral contraceptives, i.e. an insignificant increase in apo A-I level. (3) In two volunteers, apo A-I levels showed no significant variation in a 24-h period."}
{"id": "PMID:209911", "title": "Effects of dietary saturated and polyunsaturated fat on the metabolism of apolipoproteins A-I and B. Study of a patient with type IIb hyperlipoproteinaemia.", "content": "The effects of dietary saturated and polyunsaturated fat on the metabolism of apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) were studied in a patient with type IIb hyperlipoproteinaemia. On the saturated fat diet, the rate of synthesis of very low density lipoprotein apoprotein B (VLDL-apoB) was approximately twice normal, accounting for the increased plasma VLDL pool in this subject. However, 54% of the synthesized VLDL-apoB was catabolized by a pathway independent of low density lipoproteins (LDL). The metabolic conversion rate of VLDL-apoB to LDL-apoB was normal in this subject and his expanded plasma LDL-apoB pool resulted, not from increased input of the apoprotein from VLDL, but from a decrease in its fractional clearance rate. On the polyunsaturated diet, there was a significant fall in the plasma cholesterol and triglyceride concentrations and a change in the fatty acid composition of all plasma lipoprotein fractions. These changes were accompanied by a decrease in the plasma concentrations of apoA-I and apoB which resulted from a reduction of apoprotein synthetic rate.", "contents": "Effects of dietary saturated and polyunsaturated fat on the metabolism of apolipoproteins A-I and B. Study of a patient with type IIb hyperlipoproteinaemia. The effects of dietary saturated and polyunsaturated fat on the metabolism of apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) were studied in a patient with type IIb hyperlipoproteinaemia. On the saturated fat diet, the rate of synthesis of very low density lipoprotein apoprotein B (VLDL-apoB) was approximately twice normal, accounting for the increased plasma VLDL pool in this subject. However, 54% of the synthesized VLDL-apoB was catabolized by a pathway independent of low density lipoproteins (LDL). The metabolic conversion rate of VLDL-apoB to LDL-apoB was normal in this subject and his expanded plasma LDL-apoB pool resulted, not from increased input of the apoprotein from VLDL, but from a decrease in its fractional clearance rate. On the polyunsaturated diet, there was a significant fall in the plasma cholesterol and triglyceride concentrations and a change in the fatty acid composition of all plasma lipoprotein fractions. These changes were accompanied by a decrease in the plasma concentrations of apoA-I and apoB which resulted from a reduction of apoprotein synthetic rate."}
{"id": "PMID:209912", "title": "[Stability of lipid and protein composition of very low-density lipoproteins during the storage after freezing of whole serum and isolated lipoproteins (author's transl)].", "content": "The lipid and protein composition of lipoprotein is now regarded with great interest for the identification of hyperlipoproteinemias. Because this relatively time-consuming study cannot be envisaged currently in clinical services, it seems useful to analyse a storage procedure which does not affect the composition of very-low density lipoproteins, whose proportion is very important among subjects with type IV hyperlipoproteinemia. Two studies were considered, one using whole sera stored at -20 degrees C and one using very low-density lipoproteins held in the same conditions. The lipid composition was determined for triglycerides and cholesterol concentrations of total proteins, proteins soluble in tetramethylurea (apoprotein C, \"arginine-rich fraction\", and apoprotein D), and peptides CII, CIII1 and CIII2 of apoprotein C. For both procedures considered, no significant changes were seen in lipid and protein composition for periods as long as 8 weeks.", "contents": "[Stability of lipid and protein composition of very low-density lipoproteins during the storage after freezing of whole serum and isolated lipoproteins (author's transl)]. The lipid and protein composition of lipoprotein is now regarded with great interest for the identification of hyperlipoproteinemias. Because this relatively time-consuming study cannot be envisaged currently in clinical services, it seems useful to analyse a storage procedure which does not affect the composition of very-low density lipoproteins, whose proportion is very important among subjects with type IV hyperlipoproteinemia. Two studies were considered, one using whole sera stored at -20 degrees C and one using very low-density lipoproteins held in the same conditions. The lipid composition was determined for triglycerides and cholesterol concentrations of total proteins, proteins soluble in tetramethylurea (apoprotein C, \"arginine-rich fraction\", and apoprotein D), and peptides CII, CIII1 and CIII2 of apoprotein C. For both procedures considered, no significant changes were seen in lipid and protein composition for periods as long as 8 weeks."}
{"id": "PMID:209913", "title": "On the \"rapid beta\" (Rbeta) lipoprotein variant of human serum.", "content": "By visual inspection of agarose gel electrophoretograms of lipoproteins, a beta lipoprotein with increased mobility, here named \"rapid beta\" lipoprotein, has been observed. By objective measurements of the migration distances of the lipoprotein bands in 542 electrophoretograms by means of an exact ruler, this visual impression was objectively confirmed. In samples, classified by inspection as \"rapid beta\", the beta lipoprotein was found to have migrated approx. 20% further than in control samples. The \"rapid beta\" variant was initially detected in samples from grossly obese patients where it occurs frequently, but does not seem to be specific for any clinical abnormality.", "contents": "On the \"rapid beta\" (Rbeta) lipoprotein variant of human serum. By visual inspection of agarose gel electrophoretograms of lipoproteins, a beta lipoprotein with increased mobility, here named \"rapid beta\" lipoprotein, has been observed. By objective measurements of the migration distances of the lipoprotein bands in 542 electrophoretograms by means of an exact ruler, this visual impression was objectively confirmed. In samples, classified by inspection as \"rapid beta\", the beta lipoprotein was found to have migrated approx. 20% further than in control samples. The \"rapid beta\" variant was initially detected in samples from grossly obese patients where it occurs frequently, but does not seem to be specific for any clinical abnormality."}
{"id": "PMID:209914", "title": "High-density lipoprotein cholesterol, monthly variation and association with cardiovascular risk factors in 1000 forty-year-old Dutch citizens.", "content": "High density lipoprotein cholesterol (HDL chol) levels were measured in about 1000 forty-year-old residents of the town of Leiden, The Netherlands. Mean levels (+/- S.D.) in women were 48.0 +/- 11.0 mg/dl; in men 42.5 +/- 10.7 mg/dl. In March mean levels in women were about 5 mg/dl lower than in June (P less than 0.001); in men there was a similar difference between mean levels in April and June (P less than 0.002). HDL chol levels were negatively related to smoking habits, relative body weight, and in women to use of oral contraceptives. Weak positive and negative correlations between HDL chol and serum cholesterol, respectively, were found in subgroups with high and low HDL chol levels, respectively.", "contents": "High-density lipoprotein cholesterol, monthly variation and association with cardiovascular risk factors in 1000 forty-year-old Dutch citizens. High density lipoprotein cholesterol (HDL chol) levels were measured in about 1000 forty-year-old residents of the town of Leiden, The Netherlands. Mean levels (+/- S.D.) in women were 48.0 +/- 11.0 mg/dl; in men 42.5 +/- 10.7 mg/dl. In March mean levels in women were about 5 mg/dl lower than in June (P less than 0.001); in men there was a similar difference between mean levels in April and June (P less than 0.002). HDL chol levels were negatively related to smoking habits, relative body weight, and in women to use of oral contraceptives. Weak positive and negative correlations between HDL chol and serum cholesterol, respectively, were found in subgroups with high and low HDL chol levels, respectively."}
{"id": "PMID:209915", "title": "A simple spectrophotometric method for estimation of plasma angiotensin I converting enzyme activity.", "content": "The procedure described is rapid, fairly simple, and inexpensive. The method may easily be used even in a small clinical laboratory. This method, based on a specific reaction which gives a product, hippuric acid azlactone, which absorbs in the visible region, avoids the interference of reagents and solvents encountered in the UV spectrophotometric assay, in which hippuric acid is determined directly.", "contents": "A simple spectrophotometric method for estimation of plasma angiotensin I converting enzyme activity. The procedure described is rapid, fairly simple, and inexpensive. The method may easily be used even in a small clinical laboratory. This method, based on a specific reaction which gives a product, hippuric acid azlactone, which absorbs in the visible region, avoids the interference of reagents and solvents encountered in the UV spectrophotometric assay, in which hippuric acid is determined directly."}
{"id": "PMID:209916", "title": "Evaluation of an automated immunoassay procedure for apo-LDL for phenotyping type II hyperlipoproteinemia.", "content": "Apo-low density lipoproteins were determined by an automated immunoassay procedure on serum samples from 88 normolipidemic individuals and 84 hyperlipoproteinemic subjects, to establish whether this method was useful in the routine detection of type II hyperlipoproteinemia. The results obtained were compared with the cholesterol levels of the same specimens. In subjects with type II hyperlipoproteinemia, the apo low density lipoprotein levels, as well as the ratio of low density lipoprotein cholesterol/apo-low density lipoprotein were higher, as expected, than in normals or in subjects with other types of hyperlipoproteinemia. However, there was considerable overlap in individual values of both these parameters, between patients with type II hyperlipoproteinemia and normals or subjects with other types of hyperlipoproteinemia, suggesting that apo low density lipoprotein levels alone were not sufficiently discriminatory for the laboratory determination of type II hyperlipoproteinemia.", "contents": "Evaluation of an automated immunoassay procedure for apo-LDL for phenotyping type II hyperlipoproteinemia. Apo-low density lipoproteins were determined by an automated immunoassay procedure on serum samples from 88 normolipidemic individuals and 84 hyperlipoproteinemic subjects, to establish whether this method was useful in the routine detection of type II hyperlipoproteinemia. The results obtained were compared with the cholesterol levels of the same specimens. In subjects with type II hyperlipoproteinemia, the apo low density lipoprotein levels, as well as the ratio of low density lipoprotein cholesterol/apo-low density lipoprotein were higher, as expected, than in normals or in subjects with other types of hyperlipoproteinemia. However, there was considerable overlap in individual values of both these parameters, between patients with type II hyperlipoproteinemia and normals or subjects with other types of hyperlipoproteinemia, suggesting that apo low density lipoprotein levels alone were not sufficiently discriminatory for the laboratory determination of type II hyperlipoproteinemia."}
{"id": "PMID:209917", "title": "Discrete separation of HDL2 from HDL3 of human serum by means of polyacrylamide gel.", "content": "A relatively short, simple procedure is presented to separate serum high-density lipoproteins discretely into the two main classes, those with densities between 1.063 and 1.125 g/ml (HDL2) and those with densities between 1.125 and 1.210 g/ml (HDL3). A 3.5% polyacrylamide gel in 10 cm glass tubes and the use of Tris/glycine buffer, pH 8.4, will accomplish this separation. The components can be identified in several different ways, examples of which are given. This procedure will give rapid and reliable estimations of both HDL2 and HDL3, and can be used to relate their levels and proportional amounts to incidence or risk of atherosclerosis, coronary-artery disease and possibly cancer.", "contents": "Discrete separation of HDL2 from HDL3 of human serum by means of polyacrylamide gel. A relatively short, simple procedure is presented to separate serum high-density lipoproteins discretely into the two main classes, those with densities between 1.063 and 1.125 g/ml (HDL2) and those with densities between 1.125 and 1.210 g/ml (HDL3). A 3.5% polyacrylamide gel in 10 cm glass tubes and the use of Tris/glycine buffer, pH 8.4, will accomplish this separation. The components can be identified in several different ways, examples of which are given. This procedure will give rapid and reliable estimations of both HDL2 and HDL3, and can be used to relate their levels and proportional amounts to incidence or risk of atherosclerosis, coronary-artery disease and possibly cancer."}
{"id": "PMID:209918", "title": "Cushing's syndrome, nodular adrenal hyperplasia and virilizing carcinoma.", "content": "A 48-year-old hypertensive diabetic woman rapidly became virilized. Urine 17-oxo-and oxogenic steroids and plasma testosterone, androstenedione, DHEA, DHEA-sulphate and androstenediol were greatly elevated. Plasma cortisol was constantly high and was not suppressed by dexamethasone. Circulating immunoreactive ACTH was consistently detectable at 18-24 ng/l. A 450 g carcinoma arising from a nodular hyperplastic right adrenal gland was resected. Production by the tumour of 17a-hydroxypregnenolone, 17a-hydroxyprogesterone and five C-19 steroids, but very little prenenolone, progesterone or cortisol, was shown by blood sampling, tumour culture and dramatic falls after operation. The plasma cortisol fell to half, with no diurnal variation, consistent with persistent Cushing's syndrome, and the plasma ACTH rose to 55 ng/l. She died 3 months later from a myocardial infarction. Autopsy revealed a pituitary basophil adenoma at a site where radiologically there had been an indentation in the fossa floor for at least 7 years. The left adrenal gland showed nodular hyperplasia. Therefore we conclude that mild pituitary-dependent Cushing's syndrome may have been present for many years before development of a virilizing carcinoma. This case demonstrates that adrenal carcinoma in man can sometimes develop as a consequence of nodular adrenal hyperplasia which may in turn be due to long-standing trophic hyper-stimulation.", "contents": "Cushing's syndrome, nodular adrenal hyperplasia and virilizing carcinoma. A 48-year-old hypertensive diabetic woman rapidly became virilized. Urine 17-oxo-and oxogenic steroids and plasma testosterone, androstenedione, DHEA, DHEA-sulphate and androstenediol were greatly elevated. Plasma cortisol was constantly high and was not suppressed by dexamethasone. Circulating immunoreactive ACTH was consistently detectable at 18-24 ng/l. A 450 g carcinoma arising from a nodular hyperplastic right adrenal gland was resected. Production by the tumour of 17a-hydroxypregnenolone, 17a-hydroxyprogesterone and five C-19 steroids, but very little prenenolone, progesterone or cortisol, was shown by blood sampling, tumour culture and dramatic falls after operation. The plasma cortisol fell to half, with no diurnal variation, consistent with persistent Cushing's syndrome, and the plasma ACTH rose to 55 ng/l. She died 3 months later from a myocardial infarction. Autopsy revealed a pituitary basophil adenoma at a site where radiologically there had been an indentation in the fossa floor for at least 7 years. The left adrenal gland showed nodular hyperplasia. Therefore we conclude that mild pituitary-dependent Cushing's syndrome may have been present for many years before development of a virilizing carcinoma. This case demonstrates that adrenal carcinoma in man can sometimes develop as a consequence of nodular adrenal hyperplasia which may in turn be due to long-standing trophic hyper-stimulation."}
{"id": "PMID:209919", "title": "In vitro studies of the interaction of isolated Lp(a) lipoprotein and other serum lipoproteins with glycosaminoglycans.", "content": "The interaction of isolated Lp(a) lipoprotein or other lipoprotein classes with different glycosaminoglycans (GAG) bound to activated Sepharose was studied. In contrast to LDL, the Lp(a) lipoprotein did not bind to the GAG tested if sodium was used as a buffer cation. In the presence of Ca++, however, even the Lp(a) lipoprotein was bound to GAG. This type of binding, probably mediated by divalent cation bridges, is apparently not a simple function of the GAG used. Addition of GAG in solution revealed that this binding may be the only one existing under physiological conditions, and it appears possible that the Lp(a) lipoprotein is bound more firmly to GAG than is LDL under such conditions.", "contents": "In vitro studies of the interaction of isolated Lp(a) lipoprotein and other serum lipoproteins with glycosaminoglycans. The interaction of isolated Lp(a) lipoprotein or other lipoprotein classes with different glycosaminoglycans (GAG) bound to activated Sepharose was studied. In contrast to LDL, the Lp(a) lipoprotein did not bind to the GAG tested if sodium was used as a buffer cation. In the presence of Ca++, however, even the Lp(a) lipoprotein was bound to GAG. This type of binding, probably mediated by divalent cation bridges, is apparently not a simple function of the GAG used. Addition of GAG in solution revealed that this binding may be the only one existing under physiological conditions, and it appears possible that the Lp(a) lipoprotein is bound more firmly to GAG than is LDL under such conditions."}
{"id": "PMID:209920", "title": "Inter observer agreement in the assessment of the motor response of the Glasgow 'coma' scale.", "content": "The motor response of the  Glasgow 'coma' scale  is readily learned by nurses and doctors. It can be used as a reliable indicator of changes in the state of a comatose patient, as there is a high agreement rate between different observers.", "contents": "Inter observer agreement in the assessment of the motor response of the Glasgow 'coma' scale. The motor response of the  Glasgow 'coma' scale  is readily learned by nurses and doctors. It can be used as a reliable indicator of changes in the state of a comatose patient, as there is a high agreement rate between different observers."}
{"id": "PMID:209922", "title": "Gliomas: new ways of treatment?", "content": "Evidence starts to appear that immune reactions may be important in the development and growth of gliomas. The purpose of this article is to review this evidence and to mention its implications for the future.", "contents": "Gliomas: new ways of treatment? Evidence starts to appear that immune reactions may be important in the development and growth of gliomas. The purpose of this article is to review this evidence and to mention its implications for the future."}
{"id": "PMID:209923", "title": "Craniosynostosis: a new operative technique.", "content": "In the treatment of craniosynostosis several methods have been proposed to prevent craniectomies from early reclosure. New bone is formed at the edge of the craniectomy, but particularly at the outer surface of the dura. The author has developed a method to separate the edges from each other and to stop osteogenesis inside the craniectomy. The outer layer of the dura is dissected free from the inner layer folded over the edge of the groove and sutured to the outer periosteum. The operative technique and the results in 40 patients with a follow up of 17 years are described.", "contents": "Craniosynostosis: a new operative technique. In the treatment of craniosynostosis several methods have been proposed to prevent craniectomies from early reclosure. New bone is formed at the edge of the craniectomy, but particularly at the outer surface of the dura. The author has developed a method to separate the edges from each other and to stop osteogenesis inside the craniectomy. The outer layer of the dura is dissected free from the inner layer folded over the edge of the groove and sutured to the outer periosteum. The operative technique and the results in 40 patients with a follow up of 17 years are described."}
{"id": "PMID:209926", "title": "Kinking of the carotid artery: indications for surgery and surgical procedure.", "content": "In seven patients surgical correction of kinking with stenosis of the extracranial part of the carotid artery was performed. The indications for surgical treatment of carotid kinking are discussed in detail. The following criteria for surgical correction are applied: 1. symptoms of cerebral ischemia must be present; 2. position or motion of head and neck can provoke symptoms; 3. definite stenosis of the corresponding carotid artery at the level of kinking; 4. no other causes of cerebral ischemia; 5. no irreversible brain infarction. A simple and effective surgical procedure as a routine method for correction of carotid kinking is described. Only in special circumstances a more extensive open arterial reconstruction might be necessary.", "contents": "Kinking of the carotid artery: indications for surgery and surgical procedure. In seven patients surgical correction of kinking with stenosis of the extracranial part of the carotid artery was performed. The indications for surgical treatment of carotid kinking are discussed in detail. The following criteria for surgical correction are applied: 1. symptoms of cerebral ischemia must be present; 2. position or motion of head and neck can provoke symptoms; 3. definite stenosis of the corresponding carotid artery at the level of kinking; 4. no other causes of cerebral ischemia; 5. no irreversible brain infarction. A simple and effective surgical procedure as a routine method for correction of carotid kinking is described. Only in special circumstances a more extensive open arterial reconstruction might be necessary."}
{"id": "PMID:209928", "title": "Methodology for analyzing clinical neurological data: ACTH in multiple sclerosis.", "content": "From 1965 to 1968 a multicenter (USA) clinical trial was conducted to compare ACTH with placebo for the treatment of multiple sclerosis patients in a stage of acute exacerbation. Of seven evaluation systems which were used, one was a quantitative neurological examination. In this report, the quantitative neurological data have been re-evaluated using a transformation of the data which express patient scores in terms of a percentage of age- and sex-matched normal function followed by a reduction of the data into composite neurological functions vs time. The results support the positive findings of previous reports. In addition, the methodology helps to simplify the therapists' task of interpreting results by enabling him to determine how near normal function the patient came following the treatment trial.", "contents": "Methodology for analyzing clinical neurological data: ACTH in multiple sclerosis. From 1965 to 1968 a multicenter (USA) clinical trial was conducted to compare ACTH with placebo for the treatment of multiple sclerosis patients in a stage of acute exacerbation. Of seven evaluation systems which were used, one was a quantitative neurological examination. In this report, the quantitative neurological data have been re-evaluated using a transformation of the data which express patient scores in terms of a percentage of age- and sex-matched normal function followed by a reduction of the data into composite neurological functions vs time. The results support the positive findings of previous reports. In addition, the methodology helps to simplify the therapists' task of interpreting results by enabling him to determine how near normal function the patient came following the treatment trial."}
{"id": "PMID:209929", "title": "Intestinal cholecalciferol absorption in the elderly and in younger adults.", "content": "1. A method for assessing cholecalciferol absorption in man is described. 2. The intestinal absorption of [3H]cholecalciferol was studied in 20 female geriatric patients, most of whom were vitamin D-depleted. 3. The plasma [3H]cholecalciferol response after oral ingestion was significantly lower than that of a group of younger female subjects. 4. The plasma response of labelled polar metabolites of cholecalciferol was also lower in the geriatric than in the younger group, suggesting that increased removal of label by conversion into more polar metabolites could not account for the reduced plasma [3H]cholecalciferol response. 5. There was no evidence that alteration in gastrointestinal motility could account for the different rate of appearance of the labelled vitamin in the plasma in the two groups. 6. It is suggested that there is a defect in intestinal absorption of cholecalciferol in the elderly.", "contents": "Intestinal cholecalciferol absorption in the elderly and in younger adults. 1. A method for assessing cholecalciferol absorption in man is described. 2. The intestinal absorption of [3H]cholecalciferol was studied in 20 female geriatric patients, most of whom were vitamin D-depleted. 3. The plasma [3H]cholecalciferol response after oral ingestion was significantly lower than that of a group of younger female subjects. 4. The plasma response of labelled polar metabolites of cholecalciferol was also lower in the geriatric than in the younger group, suggesting that increased removal of label by conversion into more polar metabolites could not account for the reduced plasma [3H]cholecalciferol response. 5. There was no evidence that alteration in gastrointestinal motility could account for the different rate of appearance of the labelled vitamin in the plasma in the two groups. 6. It is suggested that there is a defect in intestinal absorption of cholecalciferol in the elderly."}
{"id": "PMID:209938", "title": "Biochemical and ultrastructural analysis of SV40 chromatin.", "content": "SV40 chromatin can be isolated in two forms: At moderate ionic strength (mu = 0.1-0.3) it contains histone H1 in addition to the four nucleosomal histones and has a highly condensed appearance in the electron microscope, being composed of a few closely connected large spheres [190 A (160, 220) diameter]. At high ionic strength (mu = 0.6-0.8) or after prolonged exposure to very low ionic strengths (mu less than 0.02), the compact form unfolds and the chromatin shows a typical nucleosomal morphology. Native SV40 DNA-protein complexes contain a median number of 24 nucleosomes. The number of superhelical turns does not differ in DNA obtained from the compact and the unfolded forms of chromatin. DNA-relaxing enzyme is found associated with SV40 chromatin and is capable of acting both on extraneously added circular DNA and on its own DNA in the nucleoprotein complex. Purified DNA-relaxing enzyme forms transiently nicked DNA intermediates where the enzyme can be found covalently attached to the site of the nick in the DNA. Transcriptionally active SV40 complexes undergo the same ionic-strength-dependent structural transition as that of bulk SV40 chromatin and may therefore also have a compact configuration at physiological salt concentrations.", "contents": "Biochemical and ultrastructural analysis of SV40 chromatin. SV40 chromatin can be isolated in two forms: At moderate ionic strength (mu = 0.1-0.3) it contains histone H1 in addition to the four nucleosomal histones and has a highly condensed appearance in the electron microscope, being composed of a few closely connected large spheres [190 A (160, 220) diameter]. At high ionic strength (mu = 0.6-0.8) or after prolonged exposure to very low ionic strengths (mu less than 0.02), the compact form unfolds and the chromatin shows a typical nucleosomal morphology. Native SV40 DNA-protein complexes contain a median number of 24 nucleosomes. The number of superhelical turns does not differ in DNA obtained from the compact and the unfolded forms of chromatin. DNA-relaxing enzyme is found associated with SV40 chromatin and is capable of acting both on extraneously added circular DNA and on its own DNA in the nucleoprotein complex. Purified DNA-relaxing enzyme forms transiently nicked DNA intermediates where the enzyme can be found covalently attached to the site of the nick in the DNA. Transcriptionally active SV40 complexes undergo the same ionic-strength-dependent structural transition as that of bulk SV40 chromatin and may therefore also have a compact configuration at physiological salt concentrations."}
{"id": "PMID:209947", "title": "A rapid method for isolation of the plasma membrane of the myxamoebae and swarm cells of the myxomycete Didymium iridis.", "content": "A method for the isolation of the plasma membranes of the acellular slime mould, Didymium iridis in the myxamoebae and swarm cell stages was developed using a modified dextranpolyethylene glycol aqueous two-phase polymer system. It was found to be far superior to the widely accepted technique of density gradient centrifugation concerning this cellular system. Chemical and enzymatic assays performed on the plasma membranes and other cell fractions as well as microscopic examination were used as a basis for positive identification and assessment of purity. Results of the chemical and enzymatic assays indicate that plasma membranes are recovered with high yield and purity using the modified two-phase polymer technique. The method is both rapid and effective and can be performed using low-speed centrifugation.", "contents": "A rapid method for isolation of the plasma membrane of the myxamoebae and swarm cells of the myxomycete Didymium iridis. A method for the isolation of the plasma membranes of the acellular slime mould, Didymium iridis in the myxamoebae and swarm cell stages was developed using a modified dextranpolyethylene glycol aqueous two-phase polymer system. It was found to be far superior to the widely accepted technique of density gradient centrifugation concerning this cellular system. Chemical and enzymatic assays performed on the plasma membranes and other cell fractions as well as microscopic examination were used as a basis for positive identification and assessment of purity. Results of the chemical and enzymatic assays indicate that plasma membranes are recovered with high yield and purity using the modified two-phase polymer technique. The method is both rapid and effective and can be performed using low-speed centrifugation."}
{"id": "PMID:209950", "title": "The diagnostic value of lysosomal enzyme patterns in bronchial aspirates of patients with suspected bronchial carcinoma.", "content": "The measurement of the activity of acid hydrolases and of alkaline phosphatase in bronchial aspirates obtained through bronchoscopic procedures from a series of 300 patients forms the basis for a screening program to diagnose bronchial malignant neoplasms more effectively. We define such a screening test as one permitting rapid measurements indicative of pathologic abnormalities and producing a preliminary diagnosis which, if in error, yields preferably a false-positive result. Using this approach, we demonstrated that an elevation of the activity of alkaline phosphatase or cathepsin D predicts a 50 percent likelihood of cancer, but elevation of both the concentrations of alkaline phosphatase and cathepsin D has an additive prediction of 71 percent. Data obtained in this study showed that the presence of a pulmonary tumor can cause increased levels of alkaline phosphatase or cathepsin D (or both) in bronchial aspirates before the presently accepted methods yield a diagnostic result. Furthermore, those patients with an elevated activity of alkaline phosphatase or cathepsin D (or both) but with no histologically demonstrable pulmonary carcinoma can be reexamined intermittently.", "contents": "The diagnostic value of lysosomal enzyme patterns in bronchial aspirates of patients with suspected bronchial carcinoma. The measurement of the activity of acid hydrolases and of alkaline phosphatase in bronchial aspirates obtained through bronchoscopic procedures from a series of 300 patients forms the basis for a screening program to diagnose bronchial malignant neoplasms more effectively. We define such a screening test as one permitting rapid measurements indicative of pathologic abnormalities and producing a preliminary diagnosis which, if in error, yields preferably a false-positive result. Using this approach, we demonstrated that an elevation of the activity of alkaline phosphatase or cathepsin D predicts a 50 percent likelihood of cancer, but elevation of both the concentrations of alkaline phosphatase and cathepsin D has an additive prediction of 71 percent. Data obtained in this study showed that the presence of a pulmonary tumor can cause increased levels of alkaline phosphatase or cathepsin D (or both) in bronchial aspirates before the presently accepted methods yield a diagnostic result. Furthermore, those patients with an elevated activity of alkaline phosphatase or cathepsin D (or both) but with no histologically demonstrable pulmonary carcinoma can be reexamined intermittently."}
{"id": "PMID:209951", "title": "Ultrastructure of somatotroph cells at different times in a circadian period, in mice bearing a slow growing transplanted hepatoma.", "content": "An electronmicroscopic study of STH cells from mice bearing transplanted hepatomas was performed at different time points, in a circadian period. Normal mice served as controls. The STH cells of control animals showed circadian variations inplasmic reticulum and lysosomes, which suggest increased secretion of growth hormone along the light peroid. In mice bearing hepatomas the morphologic aspect of these organelles would also indicate an increase of STH elaboration at 1200 and 1600. These changes were more remarkable than in controls and mainly consisted of hypertrophy of the Golgi complex, extended and compact endoplasmic reticulum and presence of large amounts of lysosomes. Besides, another peak of secretion seems to be present at 0000, considering the dilatation of the Golgi complex and endoplasmic reticulum cisternae. Some findings are coincident with observations made by others in the hypophysis of animals bearing transplantable tumors, where circadian periodicity was not studied. The STH cytological circadian variations could be correlated with other variations could be correlated with other variables, such as STH values in plasma and hypophysis, and DNA synthesis and mitotic activity of SS1-H hepatoma.", "contents": "Ultrastructure of somatotroph cells at different times in a circadian period, in mice bearing a slow growing transplanted hepatoma. An electronmicroscopic study of STH cells from mice bearing transplanted hepatomas was performed at different time points, in a circadian period. Normal mice served as controls. The STH cells of control animals showed circadian variations inplasmic reticulum and lysosomes, which suggest increased secretion of growth hormone along the light peroid. In mice bearing hepatomas the morphologic aspect of these organelles would also indicate an increase of STH elaboration at 1200 and 1600. These changes were more remarkable than in controls and mainly consisted of hypertrophy of the Golgi complex, extended and compact endoplasmic reticulum and presence of large amounts of lysosomes. Besides, another peak of secretion seems to be present at 0000, considering the dilatation of the Golgi complex and endoplasmic reticulum cisternae. Some findings are coincident with observations made by others in the hypophysis of animals bearing transplantable tumors, where circadian periodicity was not studied. The STH cytological circadian variations could be correlated with other variations could be correlated with other variables, such as STH values in plasma and hypophysis, and DNA synthesis and mitotic activity of SS1-H hepatoma."}
{"id": "PMID:209958", "title": "Corticosteroids: clinical pharmacology and therapeutic use.", "content": "The widespread use of corticosteroids in clinical practice emphasises the need for a thorough understanding of their metabolic effects. In general, the actions of corticosteroids on carbohydrate, protein, and lipid metabolism result in increased hepatic capacity for gluconeogenesis and enhanced catabolic actions upon muscle, skin, lymphoid, adipose and connective tissues. Because of the morbidity associated with steroid therapy, the clinician must carefully consider in each case the gains that can reasonably be expected from corticosteroid therapy versus the inevitable undesirable side effects of prolonged therapy. Thus, it is important to remember that the enhanced anti-inflammatory activity of the various synthetic analogues of cortisol is not dissociated from the expected catabolic actions of glucocorticoid hormones. Replacement therapy with physiological doses of cortisol in primary or secondary adrenal insufficiency is intended to simulate the normal daily secretion of cortisol. Short term, high dose suppressive glucocorticoid therapy is indicated in the treatment of medical emergencies such as necrotising vasculitis, status asthmaticus and anaphylactic shock. With improvement of the underlying disorder, the steroid dosage can be rapidly tapered and then discontinued over a 2 to 3 day period. Long term, high dose suppressive therapy is often commonly used to treat certain diseases (see sections 4.7.2 and 4.7.3). In this setting, suppression of the hypothalamic-pituitary-adrenal axis may persist for as long as 9 to 12 months following steroid withdrawal if steroid doses are administered in the supraphysiological range for longer than 2 weeks. In general, higher doses, longer duration of usage, and frequent daily administration are all correlated with the severity of pituitary ACTH suppression. When steroid therapy is to be withdrawn, gradual tapering of the dosage is necessary; the steroid dosage should also be given as a single morning dose if possible. Rapid or total withdrawal of the steroid therapy may be associated with exacerbation of the underlying disease or with a steroid withdrawal syndrome. An additional important point to remember in any withdrawal programme is that the steroid dosage should be appropriately increased for an exacerbation of the underlying disease or for intercurrent major stress. Alternate day therapy is recommended as a steroid maintenance programme for patients requiring high dose glucocorticoid therapy over a prolonged period of time. Thus, it is usually employed to maintain a therapeutic benefit which had previously been extablished by daily steroid treatment. Complications resulting from corticosteroid therapy include: (1) proximal muscle weakness; (2) osteopenia; (3) unmasking of latent diabetes mellitus; (4) sodium retention and/or elevation of mean arterial blood pressure; (5) adverse psychiatric reactions; (6) development of glaucoma; and (7) reactivation of latent infections (such as tuberculosis).", "contents": "Corticosteroids: clinical pharmacology and therapeutic use. The widespread use of corticosteroids in clinical practice emphasises the need for a thorough understanding of their metabolic effects. In general, the actions of corticosteroids on carbohydrate, protein, and lipid metabolism result in increased hepatic capacity for gluconeogenesis and enhanced catabolic actions upon muscle, skin, lymphoid, adipose and connective tissues. Because of the morbidity associated with steroid therapy, the clinician must carefully consider in each case the gains that can reasonably be expected from corticosteroid therapy versus the inevitable undesirable side effects of prolonged therapy. Thus, it is important to remember that the enhanced anti-inflammatory activity of the various synthetic analogues of cortisol is not dissociated from the expected catabolic actions of glucocorticoid hormones. Replacement therapy with physiological doses of cortisol in primary or secondary adrenal insufficiency is intended to simulate the normal daily secretion of cortisol. Short term, high dose suppressive glucocorticoid therapy is indicated in the treatment of medical emergencies such as necrotising vasculitis, status asthmaticus and anaphylactic shock. With improvement of the underlying disorder, the steroid dosage can be rapidly tapered and then discontinued over a 2 to 3 day period. Long term, high dose suppressive therapy is often commonly used to treat certain diseases (see sections 4.7.2 and 4.7.3). In this setting, suppression of the hypothalamic-pituitary-adrenal axis may persist for as long as 9 to 12 months following steroid withdrawal if steroid doses are administered in the supraphysiological range for longer than 2 weeks. In general, higher doses, longer duration of usage, and frequent daily administration are all correlated with the severity of pituitary ACTH suppression. When steroid therapy is to be withdrawn, gradual tapering of the dosage is necessary; the steroid dosage should also be given as a single morning dose if possible. Rapid or total withdrawal of the steroid therapy may be associated with exacerbation of the underlying disease or with a steroid withdrawal syndrome. An additional important point to remember in any withdrawal programme is that the steroid dosage should be appropriately increased for an exacerbation of the underlying disease or for intercurrent major stress. Alternate day therapy is recommended as a steroid maintenance programme for patients requiring high dose glucocorticoid therapy over a prolonged period of time. Thus, it is usually employed to maintain a therapeutic benefit which had previously been extablished by daily steroid treatment. Complications resulting from corticosteroid therapy include: (1) proximal muscle weakness; (2) osteopenia; (3) unmasking of latent diabetes mellitus; (4) sodium retention and/or elevation of mean arterial blood pressure; (5) adverse psychiatric reactions; (6) development of glaucoma; and (7) reactivation of latent infections (such as tuberculosis)."}
{"id": "PMID:209960", "title": "Field concentrations and persistence of polybrominated biphenyls in soils and solubility of PBB in natural waters.", "content": "Soil samples were collected from 28 fields which had received manure from Michigan's most highly contaminated dairy herds. The number of fields in each concentration range of PBB in soil were: 2, not detectable; 15, 0.0 to 8.0 ppb; 6, 14-102 ppb, and 5, 153 to 371 ppb. Plant tissue sampled from the 10 most highly contaminated fields contained no detectable PBB. No evidence of significant degradation of PBB was noted after 1 year incubation in soil. When 14C hexabromobiphenyl and heptabromobiphenyl isomers were incubated in soil less than 0.2% of the 14C was volatilized. Also gas chromatographic analysis of soil extracts showed no difference in recovery of the six major PBB isomers between sterilized and nonsterilized soil. Analysis of these extracts by thin layer chromatography and autoradiography showed no 14C-PBB intermediates. Photodegradation products of the major hexa- and heptabromobiphenyl isomers showed more but still minor (approximately 3%) biodegradation in soil. Much of the photodegradation products appeared bound to soil, since these products could not be extracted from soil. Photodegradation does not appear to be a significant fate of PBB in manures spread on fields since no change was noted in the relative concentrations of isomers in soil samples from our field survey. Studies with distilled, tap, river, and soil waters showed that PBB solubility was markedly influenced by water composition.", "contents": "Field concentrations and persistence of polybrominated biphenyls in soils and solubility of PBB in natural waters. Soil samples were collected from 28 fields which had received manure from Michigan's most highly contaminated dairy herds. The number of fields in each concentration range of PBB in soil were: 2, not detectable; 15, 0.0 to 8.0 ppb; 6, 14-102 ppb, and 5, 153 to 371 ppb. Plant tissue sampled from the 10 most highly contaminated fields contained no detectable PBB. No evidence of significant degradation of PBB was noted after 1 year incubation in soil. When 14C hexabromobiphenyl and heptabromobiphenyl isomers were incubated in soil less than 0.2% of the 14C was volatilized. Also gas chromatographic analysis of soil extracts showed no difference in recovery of the six major PBB isomers between sterilized and nonsterilized soil. Analysis of these extracts by thin layer chromatography and autoradiography showed no 14C-PBB intermediates. Photodegradation products of the major hexa- and heptabromobiphenyl isomers showed more but still minor (approximately 3%) biodegradation in soil. Much of the photodegradation products appeared bound to soil, since these products could not be extracted from soil. Photodegradation does not appear to be a significant fate of PBB in manures spread on fields since no change was noted in the relative concentrations of isomers in soil samples from our field survey. Studies with distilled, tap, river, and soil waters showed that PBB solubility was markedly influenced by water composition."}
{"id": "PMID:209961", "title": "Comparison of findings among residents on Michigan dairy farms and consumers of produce purchased from these farms.", "content": "Consumers who had purchased farm products from both quarantined and nonquarantined farms were examined during the cross-sectional clinical survey of 1,029 Michigan residents. Since PBB had inadvertently contaminated cattle and other farm animals, ingestion of meat, milk, eggs and other farm products was thought to have possibly resulted in significant PBB body burdens in some consumers. Findings were considered in comparison with those made among farm residents. Prevalence of symptoms in consumers of farm products from quarantined farms (CQ) was similar to that found in farmers on quarantined farms (FQ); the prevalence was lower in consumers of products from nonquarantined farms (CNQ). Liver function abnormalities were found with similar prevalence in dairy farmers and consumers. Distribution, mean and median values of PBB serum levels in consumers were found to be similar to those of dairy farmers. These results indicate that significant body burdens of PBB had been accumulated by some consumers of farm products in Michigan and that prevalence of symptoms and liver function abnormalities resembled those found among dairy farm residents.", "contents": "Comparison of findings among residents on Michigan dairy farms and consumers of produce purchased from these farms. Consumers who had purchased farm products from both quarantined and nonquarantined farms were examined during the cross-sectional clinical survey of 1,029 Michigan residents. Since PBB had inadvertently contaminated cattle and other farm animals, ingestion of meat, milk, eggs and other farm products was thought to have possibly resulted in significant PBB body burdens in some consumers. Findings were considered in comparison with those made among farm residents. Prevalence of symptoms in consumers of farm products from quarantined farms (CQ) was similar to that found in farmers on quarantined farms (FQ); the prevalence was lower in consumers of products from nonquarantined farms (CNQ). Liver function abnormalities were found with similar prevalence in dairy farmers and consumers. Distribution, mean and median values of PBB serum levels in consumers were found to be similar to those of dairy farmers. These results indicate that significant body burdens of PBB had been accumulated by some consumers of farm products in Michigan and that prevalence of symptoms and liver function abnormalities resembled those found among dairy farm residents."}
{"id": "PMID:209962", "title": "Effects of PBB on cattle. II. Gross pathology and histopathology.", "content": "Toxicosis was induced in pregnant Holstein heifers by feeding FireMaster BP-6 (polybrominated biphenyls) in daily oral doses of 25 g/head/day for 33--60 days. The individual heifers were dosed until each became moribund (days 33, 36, 39, 40, 41, or 66), at which time they were necropsied. Gross findings included dehydration, subcutaneous emphysema and hemorrhage, atrophy of the thymus, fetal death with concomitant necrosis of cotyledons, thickened wall of the gallbladder, inspissated bile, edema of abomasal folds, mucoid enteritis, linear hemorrhage and edema of the rectal mucosa, and secondary pneumonia. The livers were enlarged approximately 40%. Kidneys were approximately double the normal size and were pale tan to grey in color. The perirenal lymph nodes were enlarged and edematous. Microscopic changes were the most marked in the kidneys, gallbladder and eyelid. Extreme dilatation of collecting ducts and convoluted tubules with epithelial degenerative changes of cloudy swelling, hydropic degeneration and separation from the basement membrane were principal changes in the kidney. Hyperkeratosis with accumulations of keratin in hair follicles of the epidermis and squamous metaplasia with keratin cysts in the tarsal glands were characteristic findings in sections of eyelids. Moderate to marked hyperplasia and cystic dilatation of the mucous glands in the lamina propria were common changes in the gallbladder. Foci of fatty degeneration and glycogen depletion were observed in liver sections. Necropsy of heifers immediately after 60 days exposure to 0.25 and 250 mg/head/day of PBB showed no gross or histopathological signs indicating toxicosis. Following parturition, at approximately 220 days after the PBB doses, heifers from the 0.25 and 250 mg/head/day groups and their calves were necropsied and displayed no signs of toxicosis.", "contents": "Effects of PBB on cattle. II. Gross pathology and histopathology. Toxicosis was induced in pregnant Holstein heifers by feeding FireMaster BP-6 (polybrominated biphenyls) in daily oral doses of 25 g/head/day for 33--60 days. The individual heifers were dosed until each became moribund (days 33, 36, 39, 40, 41, or 66), at which time they were necropsied. Gross findings included dehydration, subcutaneous emphysema and hemorrhage, atrophy of the thymus, fetal death with concomitant necrosis of cotyledons, thickened wall of the gallbladder, inspissated bile, edema of abomasal folds, mucoid enteritis, linear hemorrhage and edema of the rectal mucosa, and secondary pneumonia. The livers were enlarged approximately 40%. Kidneys were approximately double the normal size and were pale tan to grey in color. The perirenal lymph nodes were enlarged and edematous. Microscopic changes were the most marked in the kidneys, gallbladder and eyelid. Extreme dilatation of collecting ducts and convoluted tubules with epithelial degenerative changes of cloudy swelling, hydropic degeneration and separation from the basement membrane were principal changes in the kidney. Hyperkeratosis with accumulations of keratin in hair follicles of the epidermis and squamous metaplasia with keratin cysts in the tarsal glands were characteristic findings in sections of eyelids. Moderate to marked hyperplasia and cystic dilatation of the mucous glands in the lamina propria were common changes in the gallbladder. Foci of fatty degeneration and glycogen depletion were observed in liver sections. Necropsy of heifers immediately after 60 days exposure to 0.25 and 250 mg/head/day of PBB showed no gross or histopathological signs indicating toxicosis. Following parturition, at approximately 220 days after the PBB doses, heifers from the 0.25 and 250 mg/head/day groups and their calves were necropsied and displayed no signs of toxicosis."}
{"id": "PMID:209963", "title": "Effects of PBBs on cattle. III. Target organ modification as shown by renal function and liver biochemistry.", "content": "Efforts were made to more clearly delineate target organs and mechanisms of toxicity for PBBs in cattle. Methods were developed to obtain sequential liver biopsies on bovine heifers which yield 0.5 to 1.0 g of tissue. PBB was fed at a dose of 250 mg/head/day to Holstein heifers for 202 days. This dose produced no clinical signs of toxicity in any of the heifers, yet this produced tissue PBB concentration of greater than 100 times the FDA tolerance in body fat of 0.3 ppm. Liver biopsies (0.5-1.0 g each) were taken at days 0, 90, and 180. The liver tissue was homogenized and microsomes were prepared. Dithionite difference spectra were determined on the carbon monoxide treated microsome suspension and the cytochrome P-450 content determined. Also, the 100,000g supernatant was saved for ornithine decarboxylase analysis as a measure of hepatocyte proliferative activity. Results of the cytochrome P-450 analysis showed a significant (p < 0.05) two-fold elevation (per gram of wet liver) by day 90 and remained significantly (p < 0.05) elevated on day 180. The cytochrome P-450 values of control animals not receiving PBBs showed no such increase with time. The biopsy procedure appeared not to adversely affect the liver cytochrome P-450 concentration in the control heifers. These results show that PBBs at a dose of 250 mg/day induced the drug metabolism system of the liver, of which the cytochrome P-450 is a part, indicating that the liver is a potential target organ for PBBs. However, this has not been shown to cause clear signs of hepatotoxicity in the cow as determined from histopathology or serum enzyme analyses. The observed elevation of gross liver weights of the PBB-treated animals might be an expected consequence of the cytochrome P-450 induction. In contrast to rodents, the kidney has been identified by histopathology as a target organ for PBB toxicity in cattle. However, renal function studies with (131)I-sodium-iodohippurate and (125)I-sodium iodothalamate in PBB treated cows indicated that PBB toxicity to the kidney did not affect glomerular filtration rate or effective renal plasma flow even though nephrotoxic effects were produced. From these studies, both liver (as expected) and kidney (unexpected) were affected by PBBs. For liver this did not result in hepatotoxicity while for kidney nephrotoxicity was produced but could not be mechanistically explained.", "contents": "Effects of PBBs on cattle. III. Target organ modification as shown by renal function and liver biochemistry. Efforts were made to more clearly delineate target organs and mechanisms of toxicity for PBBs in cattle. Methods were developed to obtain sequential liver biopsies on bovine heifers which yield 0.5 to 1.0 g of tissue. PBB was fed at a dose of 250 mg/head/day to Holstein heifers for 202 days. This dose produced no clinical signs of toxicity in any of the heifers, yet this produced tissue PBB concentration of greater than 100 times the FDA tolerance in body fat of 0.3 ppm. Liver biopsies (0.5-1.0 g each) were taken at days 0, 90, and 180. The liver tissue was homogenized and microsomes were prepared. Dithionite difference spectra were determined on the carbon monoxide treated microsome suspension and the cytochrome P-450 content determined. Also, the 100,000g supernatant was saved for ornithine decarboxylase analysis as a measure of hepatocyte proliferative activity. Results of the cytochrome P-450 analysis showed a significant (p < 0.05) two-fold elevation (per gram of wet liver) by day 90 and remained significantly (p < 0.05) elevated on day 180. The cytochrome P-450 values of control animals not receiving PBBs showed no such increase with time. The biopsy procedure appeared not to adversely affect the liver cytochrome P-450 concentration in the control heifers. These results show that PBBs at a dose of 250 mg/day induced the drug metabolism system of the liver, of which the cytochrome P-450 is a part, indicating that the liver is a potential target organ for PBBs. However, this has not been shown to cause clear signs of hepatotoxicity in the cow as determined from histopathology or serum enzyme analyses. The observed elevation of gross liver weights of the PBB-treated animals might be an expected consequence of the cytochrome P-450 induction. In contrast to rodents, the kidney has been identified by histopathology as a target organ for PBB toxicity in cattle. However, renal function studies with (131)I-sodium-iodohippurate and (125)I-sodium iodothalamate in PBB treated cows indicated that PBB toxicity to the kidney did not affect glomerular filtration rate or effective renal plasma flow even though nephrotoxic effects were produced. From these studies, both liver (as expected) and kidney (unexpected) were affected by PBBs. For liver this did not result in hepatotoxicity while for kidney nephrotoxicity was produced but could not be mechanistically explained."}
{"id": "PMID:209964", "title": "Cytogenetic and teratogenic test of polybrominated biphenyls in rodents.", "content": "Previously we reported negative terata and c-mitosis synergism of FireMaster (polybrominated biphenyls) with colchicine in subacutely treated rats. Now we report absence of chromosome aberrations from FireMaster and absence of c-mitosis synergism of FireMaster and colchicine in male mice. For the study of chromosome aberrations groups of three mice received 0, 50, or 500 mg/kg FireMaster or 4.5 mg/kg triethylenemelamine (TEM) dissolved in dimethyl sulfoxide through a single stomach gavage administration. Five hours before killing the animals were injected with 5 mg colchicine/kg. Groups of 3 mice from each treatment killed 12, 24, and 48 hr after treatment. From the bone marrow of each of 36 mice 100 metaphases were scored for gaps, chromatid and chromosome breaks, rearrangements and pulverized chromosomes. Only TEM induced chromosome damage. For detection of synergism between FireMaster and colchicine, slides prepared for chromosome analysis were also scored for metaphase and mitotic indeces. Control mice for detection of synergism were treated as for the chromosome study but were not injected with colchicine. Approximately 1000 cells were scored from each of 72 animals for determination of metaphase and mitotic indeces. FireMaster did not show c-mitosis synergism with colchicine in mice. Treatment with FireMaster did not cause visually recognizable toxicity.", "contents": "Cytogenetic and teratogenic test of polybrominated biphenyls in rodents. Previously we reported negative terata and c-mitosis synergism of FireMaster (polybrominated biphenyls) with colchicine in subacutely treated rats. Now we report absence of chromosome aberrations from FireMaster and absence of c-mitosis synergism of FireMaster and colchicine in male mice. For the study of chromosome aberrations groups of three mice received 0, 50, or 500 mg/kg FireMaster or 4.5 mg/kg triethylenemelamine (TEM) dissolved in dimethyl sulfoxide through a single stomach gavage administration. Five hours before killing the animals were injected with 5 mg colchicine/kg. Groups of 3 mice from each treatment killed 12, 24, and 48 hr after treatment. From the bone marrow of each of 36 mice 100 metaphases were scored for gaps, chromatid and chromosome breaks, rearrangements and pulverized chromosomes. Only TEM induced chromosome damage. For detection of synergism between FireMaster and colchicine, slides prepared for chromosome analysis were also scored for metaphase and mitotic indeces. Control mice for detection of synergism were treated as for the chromosome study but were not injected with colchicine. Approximately 1000 cells were scored from each of 72 animals for determination of metaphase and mitotic indeces. FireMaster did not show c-mitosis synergism with colchicine in mice. Treatment with FireMaster did not cause visually recognizable toxicity."}
{"id": "PMID:209965", "title": "Polybrominated biphenyl (PBB) in the growing pig diet.", "content": "Twelve pigs which averaged 13.7 kg were randomly allotted from litters to a corn-soybean meal grower diet containing 0, 20, or 200 ppm of polybrominated biphenyls (PPB). During a 16-week growth trial, average daily gain (kg), average daily feed (kg) and feed/gain for pigs on diets containing 0, 20, or 200 ppm of PBB, respectively, were 0.82, 2.45, 2.99; 0.67, 1.88, 2.79; 0.45, 1.23, 2.70. Mean daily gain differences between all lots were highly significant (p < 0.01). Blood from each pig was withdrawn biweekly through the first 8 weeks of the trial and at 4 week intervals thereafter. Hemoglobin and hematocrit differed significantly only at the 6 weeks bleeding, being reduced in pigs receiving 200 ppm of PBB. Erythrocyte reduced glutathione concentration and glutathione peroxidase activity were not significantly influenced by level of dietary PBB. Serum lactic dehydrogenase activity was significantly higher in control pigs than in either PBB supplemented lots at 16 weeks. There was no significant influence of PBB upon serum glutamic oxaloacetic transaminase, serum alkaline phosphatase or serum creatine phosphokinase. Based on these enzyme assays, PBB produced no evidence of significant necrosis of liver, myocardium, or skeletal muscle. There was no consistent effect of dietary PBB upon total serum protein concentration or electrophoretic profile. Pigs on either level of PBB did not have overt clinical signs of toxicity during the 16-week test period with the exception of a dermatosis on the ventral surface of two of the pigs receiving 200 ppm of PBB. There was a marked increase in liver weight of pigs receiving either level of dietary PBB. Heart, kidney, and adrenals of pigs receiving either level of dietary PBB were heavier as a percent of body weight than that of control pigs. Fat retention of PBB and urinary and fecal PBB excretion were significantly affected by dietary PBB level. Grossly, the glandular portion of the stomach appeared somewhat hyperplastic in pigs on 200 ppm of PBB. Two pigs which had received 200 ppm of PBB were placed on the control diet and over the next 14 weeks normal growth rate occurred. One of these pigs was killed and organ weights were normal. The other pig, a gilt, came into estrus. She was bred and conceived. At the end of gestation, four pigs were born. Three survived and grew normally; the one death at birth examined at gross necropsy did not reveal changes in organ size or other tissue alterations.", "contents": "Polybrominated biphenyl (PBB) in the growing pig diet. Twelve pigs which averaged 13.7 kg were randomly allotted from litters to a corn-soybean meal grower diet containing 0, 20, or 200 ppm of polybrominated biphenyls (PPB). During a 16-week growth trial, average daily gain (kg), average daily feed (kg) and feed/gain for pigs on diets containing 0, 20, or 200 ppm of PBB, respectively, were 0.82, 2.45, 2.99; 0.67, 1.88, 2.79; 0.45, 1.23, 2.70. Mean daily gain differences between all lots were highly significant (p < 0.01). Blood from each pig was withdrawn biweekly through the first 8 weeks of the trial and at 4 week intervals thereafter. Hemoglobin and hematocrit differed significantly only at the 6 weeks bleeding, being reduced in pigs receiving 200 ppm of PBB. Erythrocyte reduced glutathione concentration and glutathione peroxidase activity were not significantly influenced by level of dietary PBB. Serum lactic dehydrogenase activity was significantly higher in control pigs than in either PBB supplemented lots at 16 weeks. There was no significant influence of PBB upon serum glutamic oxaloacetic transaminase, serum alkaline phosphatase or serum creatine phosphokinase. Based on these enzyme assays, PBB produced no evidence of significant necrosis of liver, myocardium, or skeletal muscle. There was no consistent effect of dietary PBB upon total serum protein concentration or electrophoretic profile. Pigs on either level of PBB did not have overt clinical signs of toxicity during the 16-week test period with the exception of a dermatosis on the ventral surface of two of the pigs receiving 200 ppm of PBB. There was a marked increase in liver weight of pigs receiving either level of dietary PBB. Heart, kidney, and adrenals of pigs receiving either level of dietary PBB were heavier as a percent of body weight than that of control pigs. Fat retention of PBB and urinary and fecal PBB excretion were significantly affected by dietary PBB level. Grossly, the glandular portion of the stomach appeared somewhat hyperplastic in pigs on 200 ppm of PBB. Two pigs which had received 200 ppm of PBB were placed on the control diet and over the next 14 weeks normal growth rate occurred. One of these pigs was killed and organ weights were normal. The other pig, a gilt, came into estrus. She was bred and conceived. At the end of gestation, four pigs were born. Three survived and grew normally; the one death at birth examined at gross necropsy did not reveal changes in organ size or other tissue alterations."}
{"id": "PMID:209966", "title": "Effect of diet on the hepatotoxicity of polybrominated biphenyls (FireMaster PB-6).", "content": "The consumption of diets formulated with Cruciferae vegetables, e.g., cauliflower, cabbage, and Brussels sprouts, has been shown to result in a stimulation of the intestinal and hepatic microsomal enzyme systems in rats. This study was designed to determine if this increase in intestinal and hepatic microsomal enzyme activity affected the hepatic response to polybrominated biphenyls (PBB). After three weeks of consuming either a semipurified or 25% cauliflower leaf-supplemented diet (CLD), male Sprague-Dawley rats were maintained for an additional 20 days on their respective diets containing either 0, 1, or 50 ppm PBB. A significant decrease in body weights, but not feed efficiency, was observed over all levels of PBB in animals consuming CLD compared to semipurified diets; consumption of up to 50 ppm of PBB had no effect on body weights with either diet. Relative liver weights (RLW), hepatic aryl hydrocarbon hydroxylase (AHH), N- and O-demethylase, as well as intestinal AHH were all increased in CLD-consuming animals before the addition of PBB. While PBB supplementation alone resulted in increased RLW, hepatic AHH, N- and O-demethylase, microsomal protein, and cytochrome P-450, rats consuming cauliflower diets + PBB had even higher RLW and N- and O-demethylase activity and microsomal protein concentrations. Hepatic PBB residue and total hepatic lipids were significantly reduced in CLD groups receiving 50 ppm PBB. These results suggest that the antitoxic effects of certain vegetables are related to more rapid metabolism and excretion of xenobiotic compounds.", "contents": "Effect of diet on the hepatotoxicity of polybrominated biphenyls (FireMaster PB-6). The consumption of diets formulated with Cruciferae vegetables, e.g., cauliflower, cabbage, and Brussels sprouts, has been shown to result in a stimulation of the intestinal and hepatic microsomal enzyme systems in rats. This study was designed to determine if this increase in intestinal and hepatic microsomal enzyme activity affected the hepatic response to polybrominated biphenyls (PBB). After three weeks of consuming either a semipurified or 25% cauliflower leaf-supplemented diet (CLD), male Sprague-Dawley rats were maintained for an additional 20 days on their respective diets containing either 0, 1, or 50 ppm PBB. A significant decrease in body weights, but not feed efficiency, was observed over all levels of PBB in animals consuming CLD compared to semipurified diets; consumption of up to 50 ppm of PBB had no effect on body weights with either diet. Relative liver weights (RLW), hepatic aryl hydrocarbon hydroxylase (AHH), N- and O-demethylase, as well as intestinal AHH were all increased in CLD-consuming animals before the addition of PBB. While PBB supplementation alone resulted in increased RLW, hepatic AHH, N- and O-demethylase, microsomal protein, and cytochrome P-450, rats consuming cauliflower diets + PBB had even higher RLW and N- and O-demethylase activity and microsomal protein concentrations. Hepatic PBB residue and total hepatic lipids were significantly reduced in CLD groups receiving 50 ppm PBB. These results suggest that the antitoxic effects of certain vegetables are related to more rapid metabolism and excretion of xenobiotic compounds."}
{"id": "PMID:209967", "title": "Responses of nonhuman primates to a polybrominated biphenyl mixture.", "content": "In a series of experiments, rhesus monkeys have been given in their diets 0.3, 1.5, and 25 ppm of a commercial polybrominated biphenyl (PBB) (as FireMaster FF-1). The seven adult female monkeys receiving 0.3 ppm PBB have been on the treatment regime for 15 months and have consumed over 22 mg of PBB. During the initial 6 months of exposure, they lost weight and 2 of the animals develop sterile abscesses. At 6 months, 4 of the 7 animals had flattened and lengthened serum progesterone peaks. This change was correlated with an increase in length of their menstrual cycles. After 6 months of PBB exposure, the animals were bred. Two of the 7 animals showed excessive and prolonged implantation bleeding. Two abortions and 5 live births were recorded. All of the experimental infants were smaller than the controls at birth. The animals receiving a diet containing 1.5 ppm PBB for 36 weeks (total intake 70 mg) have shown a moderate weight loss and decrease in serum cholesterol. Similar changes have also been recorded in the group given the 25 ppm PBB diet for 14 weeks (approximately 500 mg total intake). In addition, these animals have also developed a hyperplastic gastritis.", "contents": "Responses of nonhuman primates to a polybrominated biphenyl mixture. In a series of experiments, rhesus monkeys have been given in their diets 0.3, 1.5, and 25 ppm of a commercial polybrominated biphenyl (PBB) (as FireMaster FF-1). The seven adult female monkeys receiving 0.3 ppm PBB have been on the treatment regime for 15 months and have consumed over 22 mg of PBB. During the initial 6 months of exposure, they lost weight and 2 of the animals develop sterile abscesses. At 6 months, 4 of the 7 animals had flattened and lengthened serum progesterone peaks. This change was correlated with an increase in length of their menstrual cycles. After 6 months of PBB exposure, the animals were bred. Two of the 7 animals showed excessive and prolonged implantation bleeding. Two abortions and 5 live births were recorded. All of the experimental infants were smaller than the controls at birth. The animals receiving a diet containing 1.5 ppm PBB for 36 weeks (total intake 70 mg) have shown a moderate weight loss and decrease in serum cholesterol. Similar changes have also been recorded in the group given the 25 ppm PBB diet for 14 weeks (approximately 500 mg total intake). In addition, these animals have also developed a hyperplastic gastritis."}
{"id": "PMID:209968", "title": "FireMaster BP-6: fractionation, metabolic and enzyme induction studies.", "content": "FireMaster BP-6 is a commercial polybrominated biphenyl (PBB) preparation containing a complex mixture of isomers with the major component being identified as 2,2',4,4',5,5'-hexabromobiphenyl. Column chromatographic techniques have been developed in which the crude FireMaster is separated into three fractions, F1, F2, and F3, in increasing order of polarity. F1 consists of highly purified 2,2',4,4',5,5'-hexabromobiphenyl (94%) whereas F2-F3 contain less of this isomer and correspondingly more of the other bromobiphenyl components. Previously we have shown that crude FireMaster BP-6 is metabolized in mammals to give hydroxylated degradation products and the metabolism of F1, not unexpectedly, gives comparable results. It is well known that PBBs are effective inducers of diverse microsomal enzymes including including the aryl hydrocarbon hydroxylase (AHH) system. The effects of FireMaster BP-6 and F1-F3 as AHH inducers have been investigated by using the following approach: the substrates used to monitor AHH activity are model halogenated aromatic compounds; the levels of metabolites and metabolite conjugates formed have been quantitated for control and induced enzymes; the levels of macromolecular adducts have also been quantitated for the inducers. This approach thus not only measures the rate of increase of detoxification products (metabolites and metabolite conjugates) but also monitors the macromolecule adduct formation which represents a toxification route. The effects of the PBBs as AHH inducers will be discussed in terms of the above approach.", "contents": "FireMaster BP-6: fractionation, metabolic and enzyme induction studies. FireMaster BP-6 is a commercial polybrominated biphenyl (PBB) preparation containing a complex mixture of isomers with the major component being identified as 2,2',4,4',5,5'-hexabromobiphenyl. Column chromatographic techniques have been developed in which the crude FireMaster is separated into three fractions, F1, F2, and F3, in increasing order of polarity. F1 consists of highly purified 2,2',4,4',5,5'-hexabromobiphenyl (94%) whereas F2-F3 contain less of this isomer and correspondingly more of the other bromobiphenyl components. Previously we have shown that crude FireMaster BP-6 is metabolized in mammals to give hydroxylated degradation products and the metabolism of F1, not unexpectedly, gives comparable results. It is well known that PBBs are effective inducers of diverse microsomal enzymes including including the aryl hydrocarbon hydroxylase (AHH) system. The effects of FireMaster BP-6 and F1-F3 as AHH inducers have been investigated by using the following approach: the substrates used to monitor AHH activity are model halogenated aromatic compounds; the levels of metabolites and metabolite conjugates formed have been quantitated for control and induced enzymes; the levels of macromolecular adducts have also been quantitated for the inducers. This approach thus not only measures the rate of increase of detoxification products (metabolites and metabolite conjugates) but also monitors the macromolecule adduct formation which represents a toxification route. The effects of the PBBs as AHH inducers will be discussed in terms of the above approach."}
{"id": "PMID:209969", "title": "Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes.", "content": "Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function.", "contents": "Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes. Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function."}
{"id": "PMID:209970", "title": "Induction of drug metabolizing enzymes in polybrominated biphenyl-fed lactating rats and their pups.", "content": "Polybrominated biphenyls (PBBs) cause a mixed-type (phenobarbital- plus 3-methylcholanthrene-like) induction of liver microsomal drug metabolizing enzymes in rats. However, 2,2',4,4',5,5'-hexabromobiphenyl and 2,2',3,4,4',5,5'-heptabromobiphenyl, which together comprise less than 80% of PBBs (FireMaster), were shown to be strictly phenobarbital-type inducers. Other components (unidentified) must therefore cause the 3-methylcholanthrene-like effects. The potential for PBBs to exert effects on neonates through milk was examined. Lactating rats were fed 0, 0.1, 1.0, or 10 ppm FireMaster for the 18 days following delivery, at which time mothers and most pups were sacrificed. Pups nursing from mothers fed 10 ppm PBBs showed significant increases in liver weights and microsomal protein, and both mothers and pups had increased cytochrome P-450, aminopyrine demethylation, benzo[a]pyrene hydroxylation, and UDP-glucuronyltransferase. Pups nursing from rats fed 1.0 ppm had increases in microsomal protein, cytochrome P-450, aminopyrine demethylation, and benzo[a]pyrene hydroxylation, while their mothers were unaffected. Several pups from the 0, 0.1, and 1.0 ppm groups were maintained on their mother's diets, raised, and allowed to mate. Their pups showed much the same responses to PBBs as did the original group of pups. The effects on both generations of adult female rats were also comparable. PBBs cause a mixed-type induction in both lactating rats and their nursing pups; PBB components responsible for both aspects of this induction must be transmitted through milk. Nursing rats are approximately tenfold more sensitive to the effects of PBBs in their mother's diets than are the dams. The approximate no-effect level for microsomal induction in nursing rats is 0.1 ppm PBBs in the diet of the adult.", "contents": "Induction of drug metabolizing enzymes in polybrominated biphenyl-fed lactating rats and their pups. Polybrominated biphenyls (PBBs) cause a mixed-type (phenobarbital- plus 3-methylcholanthrene-like) induction of liver microsomal drug metabolizing enzymes in rats. However, 2,2',4,4',5,5'-hexabromobiphenyl and 2,2',3,4,4',5,5'-heptabromobiphenyl, which together comprise less than 80% of PBBs (FireMaster), were shown to be strictly phenobarbital-type inducers. Other components (unidentified) must therefore cause the 3-methylcholanthrene-like effects. The potential for PBBs to exert effects on neonates through milk was examined. Lactating rats were fed 0, 0.1, 1.0, or 10 ppm FireMaster for the 18 days following delivery, at which time mothers and most pups were sacrificed. Pups nursing from mothers fed 10 ppm PBBs showed significant increases in liver weights and microsomal protein, and both mothers and pups had increased cytochrome P-450, aminopyrine demethylation, benzo[a]pyrene hydroxylation, and UDP-glucuronyltransferase. Pups nursing from rats fed 1.0 ppm had increases in microsomal protein, cytochrome P-450, aminopyrine demethylation, and benzo[a]pyrene hydroxylation, while their mothers were unaffected. Several pups from the 0, 0.1, and 1.0 ppm groups were maintained on their mother's diets, raised, and allowed to mate. Their pups showed much the same responses to PBBs as did the original group of pups. The effects on both generations of adult female rats were also comparable. PBBs cause a mixed-type induction in both lactating rats and their nursing pups; PBB components responsible for both aspects of this induction must be transmitted through milk. Nursing rats are approximately tenfold more sensitive to the effects of PBBs in their mother's diets than are the dams. The approximate no-effect level for microsomal induction in nursing rats is 0.1 ppm PBBs in the diet of the adult."}
{"id": "PMID:209971", "title": "Toxicity of PBBs with special reference to porphyrinogenic action and spectral interaction with hepatic cytochrome P-450.", "content": "Some of the polyhalogenated aromatic compounds (PHAs) which are able to produce porphyria are presently known as environmental contaminants. Chronic exposure to PHAs causes hepatic porphyria in different species. Qualitatively PBBs act comparable to PHAs. An increase in accumulation of porphyrins caused by PHAs is not simply related to an increase of delta-ALAS activity in liver. Heme cannot exert a feedback when porphyria develops. Induction of P-450 mediated drug enzymes is needed. The PHAs interact with P-450 in vitro. The PHAs are converted into a reactive intermediate, not a known metabolite, which depletes liver GSH and then becomes reactive to tissue structures. Mitochondria are damaged; fluorescence of porphyrins is detected in the region of central veins where degenerative change in hepatocytes is most marked. A possible pathological change in the cell membrane permeability is assumed too. In this porphyric stage uropophyrinogen decarboxylase (urogen decarboxylase) is inhibited. The proportion of steroid hormones product by ovaries and testes compared to each other are possibly involved in sensitivity to porphyrinogenic compounds.", "contents": "Toxicity of PBBs with special reference to porphyrinogenic action and spectral interaction with hepatic cytochrome P-450. Some of the polyhalogenated aromatic compounds (PHAs) which are able to produce porphyria are presently known as environmental contaminants. Chronic exposure to PHAs causes hepatic porphyria in different species. Qualitatively PBBs act comparable to PHAs. An increase in accumulation of porphyrins caused by PHAs is not simply related to an increase of delta-ALAS activity in liver. Heme cannot exert a feedback when porphyria develops. Induction of P-450 mediated drug enzymes is needed. The PHAs interact with P-450 in vitro. The PHAs are converted into a reactive intermediate, not a known metabolite, which depletes liver GSH and then becomes reactive to tissue structures. Mitochondria are damaged; fluorescence of porphyrins is detected in the region of central veins where degenerative change in hepatocytes is most marked. A possible pathological change in the cell membrane permeability is assumed too. In this porphyric stage uropophyrinogen decarboxylase (urogen decarboxylase) is inhibited. The proportion of steroid hormones product by ovaries and testes compared to each other are possibly involved in sensitivity to porphyrinogenic compounds."}
{"id": "PMID:209972", "title": "Relation of DDE and PBB serum levels in farm residents, consumers, and Michigan Chemical Corporation employees.", "content": "Results of serum PBB determinations on 524 Michigan diary farm residents and consumers of products from the farms, 55 chemical workers, and 56 Wisconsin farm residents are reported. Mean and median values were highest for the chemical workers, followed by consumers from and residents of quarantined and nonquarantined farms. Serum DDE was higher among chemical workers, but was similar for all other groups. Statistical analysis of serum of PPB and serum DDE levels was done with respect to quarantine status, age, sex, and obesity. The most significant correlate with PBB was quarantine status. Serum DDE, age, sex, or obesity were not consistently correlated with serum PBB. For DDE, age was invariably the most significant correlate. Both serum PBB and DDE were higher in males than females in husband-wife pairs in most cases, although the differences occurred less frequently among older age groups. These results support the hypothesis that PBB exposure was a recent interim exposure whereas DDE exposure has been cumulative throughout a person's lifetime. Higher PBB and DDE mean concentrations in serum of Michigan Chemical workers suggests an occupational exposure to these chemicals.", "contents": "Relation of DDE and PBB serum levels in farm residents, consumers, and Michigan Chemical Corporation employees. Results of serum PBB determinations on 524 Michigan diary farm residents and consumers of products from the farms, 55 chemical workers, and 56 Wisconsin farm residents are reported. Mean and median values were highest for the chemical workers, followed by consumers from and residents of quarantined and nonquarantined farms. Serum DDE was higher among chemical workers, but was similar for all other groups. Statistical analysis of serum of PPB and serum DDE levels was done with respect to quarantine status, age, sex, and obesity. The most significant correlate with PBB was quarantine status. Serum DDE, age, sex, or obesity were not consistently correlated with serum PBB. For DDE, age was invariably the most significant correlate. Both serum PBB and DDE were higher in males than females in husband-wife pairs in most cases, although the differences occurred less frequently among older age groups. These results support the hypothesis that PBB exposure was a recent interim exposure whereas DDE exposure has been cumulative throughout a person's lifetime. Higher PBB and DDE mean concentrations in serum of Michigan Chemical workers suggests an occupational exposure to these chemicals."}
{"id": "PMID:209973", "title": "A simple technique for fat biopsy of PBB-exposed individuals.", "content": "A simple nonsurgical technique of obtaining fat samples by aspiration from the gluteal prominence was developed by Hirsh in 1960 and has been in use in our Nutrition Clinic at the Mount Sinai Hospital for several years. We have modified it for field use and the analysis of fat-soluble hydrocarbon residues. All the materials which will contain the fat sample to be analyzed are washed with acetone and pesticide residue-free hexane, and a 15 gauge needle and 33 cc syringe are sterilized. Aspiration of fat from the lateral gluteal prominence is accomplished under local xylocaine anesthetic. The anesthetic also serves as the vehicle into which the fat is broken by the shearing action of the 15 gauge needle. Fat particles are sucked into the syringe by a constant vacuum kept on the syringe during lateral movement of the needle under (and parallel to) the skin within the gluteal fat pad; 200--500 ml of fat can be obtained for hydrocarbon residue analysis. The only complications have been some mild hematomas at the site of the aspiration. The method avoids surgical biopsy and sutures and takes about 7--8 min.", "contents": "A simple technique for fat biopsy of PBB-exposed individuals. A simple nonsurgical technique of obtaining fat samples by aspiration from the gluteal prominence was developed by Hirsh in 1960 and has been in use in our Nutrition Clinic at the Mount Sinai Hospital for several years. We have modified it for field use and the analysis of fat-soluble hydrocarbon residues. All the materials which will contain the fat sample to be analyzed are washed with acetone and pesticide residue-free hexane, and a 15 gauge needle and 33 cc syringe are sterilized. Aspiration of fat from the lateral gluteal prominence is accomplished under local xylocaine anesthetic. The anesthetic also serves as the vehicle into which the fat is broken by the shearing action of the 15 gauge needle. Fat particles are sucked into the syringe by a constant vacuum kept on the syringe during lateral movement of the needle under (and parallel to) the skin within the gluteal fat pad; 200--500 ml of fat can be obtained for hydrocarbon residue analysis. The only complications have been some mild hematomas at the site of the aspiration. The method avoids surgical biopsy and sutures and takes about 7--8 min."}
{"id": "PMID:209974", "title": "Investigation of the health status of Michigan chemical corporation employees.", "content": "Clinical findings are reported for a group of 55 employees of the Michigan Chemical Corporation which manufactured FireMaster BP-6 from 1970 to 1974, in addition to a variety of other halogenated fire retardant chemicals. The results are compared with those from a group of male farm residents and consumers from Michigan examined at the same time. An increased prevalence of chest and skin symptoms was observed, compared with farmers. Skin symptoms were more prevalent among former PBB production personnel. Musculosketal symptoms were less prevalent among these workers than among farmers. Serum PBB concentrations are signicantly higher than among farmers. Blood chemistry results were similar for workers and farmers. However, both groups exhibited a significantly higher prevalence of elevated liver function tests (SGOT, SPGT) than a control population of nonexposed farmers. Both farmers and chemical workers showed an association of elevated CEA with serum PBB greater than 10 ppb.", "contents": "Investigation of the health status of Michigan chemical corporation employees. Clinical findings are reported for a group of 55 employees of the Michigan Chemical Corporation which manufactured FireMaster BP-6 from 1970 to 1974, in addition to a variety of other halogenated fire retardant chemicals. The results are compared with those from a group of male farm residents and consumers from Michigan examined at the same time. An increased prevalence of chest and skin symptoms was observed, compared with farmers. Skin symptoms were more prevalent among former PBB production personnel. Musculosketal symptoms were less prevalent among these workers than among farmers. Serum PBB concentrations are signicantly higher than among farmers. Blood chemistry results were similar for workers and farmers. However, both groups exhibited a significantly higher prevalence of elevated liver function tests (SGOT, SPGT) than a control population of nonexposed farmers. Both farmers and chemical workers showed an association of elevated CEA with serum PBB greater than 10 ppb."}
{"id": "PMID:209975", "title": "Polybrominated biphenyl (PBB) contamination of the Pine River, Gratiot, and Midland Counties, Michigan.", "content": "Michigan Chemical Corporation, St. Louis, Michigan manufactured PBB from 1970 until November 20, 1974. Studies in 1974 showed significant quantities of PBB in effluent discharged from the facility and in water, fish, ducks, and sediments from the Pine River. Fish uptake rates and bioconcentration factors were estimated. Followup surveys over the three year period since the termination of PBB production indicate a decline in PBB loadings to the river but no significant corresponding decline of PBB levels in sediments, fish and duck tissue. A Michigan Department of Public Health warning against consumption of Pine River fish from St. Louis downstream to its confluence with Chippewa River remains in effect.", "contents": "Polybrominated biphenyl (PBB) contamination of the Pine River, Gratiot, and Midland Counties, Michigan. Michigan Chemical Corporation, St. Louis, Michigan manufactured PBB from 1970 until November 20, 1974. Studies in 1974 showed significant quantities of PBB in effluent discharged from the facility and in water, fish, ducks, and sediments from the Pine River. Fish uptake rates and bioconcentration factors were estimated. Followup surveys over the three year period since the termination of PBB production indicate a decline in PBB loadings to the river but no significant corresponding decline of PBB levels in sediments, fish and duck tissue. A Michigan Department of Public Health warning against consumption of Pine River fish from St. Louis downstream to its confluence with Chippewa River remains in effect."}
{"id": "PMID:209976", "title": "Carcinoembryonic antigen (CEA) plasma levels in Michigan and Wisconsin dairy farmers.", "content": "Carcionogenic embryonic antigen (CEA) titers were determined for 611 Michigan farmers exposed to PBB and a control nonexposed population of 139 Wisconsin farmers. The overall prevalence of elevated CEA titers was slightly higher in the Michigan study group, but the difference was not statistically significant. Smoking and/or significant past or present conditions (inflammatory bowel disease, ulcers, polyps, liver disease, chronic lung disease, or malignancies) were found to result in higher prevalence of elevated CEA titers, in both the Michigan study group and the Wisconsin control group, thus confirming previous reports. In addition, serum PBB concentrations appeared to be positively correlated with CEA titers. The possibility that the effect of PBB concentrations appeared to be positively correlated with CEA titers. The possibility that the effect of PBB may be additive to that of other factors which are known to result in an increased prevalence of elevated CEA titers is discussed.", "contents": "Carcinoembryonic antigen (CEA) plasma levels in Michigan and Wisconsin dairy farmers. Carcionogenic embryonic antigen (CEA) titers were determined for 611 Michigan farmers exposed to PBB and a control nonexposed population of 139 Wisconsin farmers. The overall prevalence of elevated CEA titers was slightly higher in the Michigan study group, but the difference was not statistically significant. Smoking and/or significant past or present conditions (inflammatory bowel disease, ulcers, polyps, liver disease, chronic lung disease, or malignancies) were found to result in higher prevalence of elevated CEA titers, in both the Michigan study group and the Wisconsin control group, thus confirming previous reports. In addition, serum PBB concentrations appeared to be positively correlated with CEA titers. The possibility that the effect of PBB concentrations appeared to be positively correlated with CEA titers. The possibility that the effect of PBB may be additive to that of other factors which are known to result in an increased prevalence of elevated CEA titers is discussed."}
{"id": "PMID:209977", "title": "Comparative neurobehavioral study of a polybrominated biphenyl-exposed population in Michigan and a nonexposed group in Wisconsin.", "content": "An analysis of findings regarding the prevalence and time course of symptoms and the results of neurobehavioral testing among Michigan and Wisconsin dairy farmers, is reported. Reviewed are: (1) differences in the prevalence of neurological symptoms at the time of examination; (2) differences in the incidence and time course of symptoms for the period 1972--1976; (3) differences among populations and subgroups (sex and age) regarding performance test scores; (4) correlations between performance test scores and neurological symptoms; and (5) correlations between serum PBB levels as indicators of exposure and performance tests and neurological symptoms.", "contents": "Comparative neurobehavioral study of a polybrominated biphenyl-exposed population in Michigan and a nonexposed group in Wisconsin. An analysis of findings regarding the prevalence and time course of symptoms and the results of neurobehavioral testing among Michigan and Wisconsin dairy farmers, is reported. Reviewed are: (1) differences in the prevalence of neurological symptoms at the time of examination; (2) differences in the incidence and time course of symptoms for the period 1972--1976; (3) differences among populations and subgroups (sex and age) regarding performance test scores; (4) correlations between performance test scores and neurological symptoms; and (5) correlations between serum PBB levels as indicators of exposure and performance tests and neurological symptoms."}
{"id": "PMID:209978", "title": "PBB homologs in sera of Michigan dairy farmers and Michigan chemical workers.", "content": "In November, 1976 the Environmental Sciences Laboratory of the Mount Sinai School of Medicine, examined 1029 persons in Michigan for the potential health effects of exposure to PBB. Included in this group were 55 persons from Michigan Chemical Corporation and 237 farming families. Blood serum was analyzed for PBB. FireMaster FF-1 contains several bromobiphenyl components, the major constituent being approximately 60% 2,4,4,2'4'4'-hexabromobiphenyl. Other PBB homologs identifiable as peaks by gas chromatography--mass spectrometry include two pentabromobiphenyl peaks, three additional hexabromobiphenyl peaks, and two heptabromobiphenyl peaks. The relative concentrations, with respect to the major hexabromobiphenyl peak, of these minor constituents (1--20%) of PBB were different for persons from Michigan Chemical Corporation and for farmers. Penta-, hexa-, and hepta-bromobiphenyl components in serum samples analyzed from farming families from Michigan Chemical Corporation employees were compared with relative concentrations of these homologs in FireMaster mixture and in tissue and blood samples from rats fed FireMaster FF-1. Varying concentrations of these PBB components are attributed to different routes of exposure and the relative ease of metabolism and excretion of one pentabromobiphenyl component.", "contents": "PBB homologs in sera of Michigan dairy farmers and Michigan chemical workers. In November, 1976 the Environmental Sciences Laboratory of the Mount Sinai School of Medicine, examined 1029 persons in Michigan for the potential health effects of exposure to PBB. Included in this group were 55 persons from Michigan Chemical Corporation and 237 farming families. Blood serum was analyzed for PBB. FireMaster FF-1 contains several bromobiphenyl components, the major constituent being approximately 60% 2,4,4,2'4'4'-hexabromobiphenyl. Other PBB homologs identifiable as peaks by gas chromatography--mass spectrometry include two pentabromobiphenyl peaks, three additional hexabromobiphenyl peaks, and two heptabromobiphenyl peaks. The relative concentrations, with respect to the major hexabromobiphenyl peak, of these minor constituents (1--20%) of PBB were different for persons from Michigan Chemical Corporation and for farmers. Penta-, hexa-, and hepta-bromobiphenyl components in serum samples analyzed from farming families from Michigan Chemical Corporation employees were compared with relative concentrations of these homologs in FireMaster mixture and in tissue and blood samples from rats fed FireMaster FF-1. Varying concentrations of these PBB components are attributed to different routes of exposure and the relative ease of metabolism and excretion of one pentabromobiphenyl component."}
{"id": "PMID:209979", "title": "Unanticipated prevalence of symptoms among dairy farmers in Michigan and Wisconsin.", "content": "Adverse human health effects resulting from exposure to polychlorinated biphenyls (PBBs) were unknown until the accidental contamination of Michigan dairy farm animal feed in 1973-1974. Human exposure resulted from the consumption of contaminated meat, milk, dairy products, and eggs. In November 1976, the Environmental Sciences Laboratory conducted comprehensive examinations of 933 farmers and residents in Mighigan who were likely to have consumed farm products contaminated with PBB. A comparison group of 229 Wisconsin dairy farmers were examined in March 1977 and the same scientific and medical staffs that conducted the Michigan survey were responsible and the same procedures used. A complete history of symptomatology by organ system, including year of first onset, duration, frequency, and severity of each symptom was obtained by a physician on all adults examined. Statistical analysis of the prevalence of symptoms at the time of examination or during the preceding year in the Michigan and Wisconsin populations studied found the Michigan group to have a significantly higher prevalence of skin, neurological and musculoskeletal symptoms. The increase was seen among the younger age groups 16-35 and 36-55. Michigan females had a higher prevalence of neurological symptoms than the Michigan males. The existing differences could not be explained without considering an etiologic role for exposure to PBB.", "contents": "Unanticipated prevalence of symptoms among dairy farmers in Michigan and Wisconsin. Adverse human health effects resulting from exposure to polychlorinated biphenyls (PBBs) were unknown until the accidental contamination of Michigan dairy farm animal feed in 1973-1974. Human exposure resulted from the consumption of contaminated meat, milk, dairy products, and eggs. In November 1976, the Environmental Sciences Laboratory conducted comprehensive examinations of 933 farmers and residents in Mighigan who were likely to have consumed farm products contaminated with PBB. A comparison group of 229 Wisconsin dairy farmers were examined in March 1977 and the same scientific and medical staffs that conducted the Michigan survey were responsible and the same procedures used. A complete history of symptomatology by organ system, including year of first onset, duration, frequency, and severity of each symptom was obtained by a physician on all adults examined. Statistical analysis of the prevalence of symptoms at the time of examination or during the preceding year in the Michigan and Wisconsin populations studied found the Michigan group to have a significantly higher prevalence of skin, neurological and musculoskeletal symptoms. The increase was seen among the younger age groups 16-35 and 36-55. Michigan females had a higher prevalence of neurological symptoms than the Michigan males. The existing differences could not be explained without considering an etiologic role for exposure to PBB."}
{"id": "PMID:209980", "title": "Effects of polybrominated biphenyls (PBB) on immune response in rodents.", "content": "Studies were performed to investigate the effects of FireMaster FF-1, a chemical fire retardant consisting of a mixture of polybrominated biphenyls (PBB), on immune functions in mice and rats. Animals received 22 daily treatments of 0.03, 0.3, 3.0, or 30 mg PBB/kg body weight in a period covering 30 days. PBB exposure severely depressed cell mediated immunity in both mice and rats at the higher dosage levels as indicated by depressed responsiveness of splenic lymphocytes to mitogenic stimulation by polyclonal T-cell activators. Additionally, humoral immunity was depressed in mice at the 30.0 ppm dosage level. Assays for humoral immune functions included antibody production, serum immunoglobulin levels, and mitogenic stimulation of splenic lymphocytes to a polyclonal B-cell activator. These studies indicate that PBB exposure can lead to suppression of both humoral and particularly cell-mediated immune responses.", "contents": "Effects of polybrominated biphenyls (PBB) on immune response in rodents. Studies were performed to investigate the effects of FireMaster FF-1, a chemical fire retardant consisting of a mixture of polybrominated biphenyls (PBB), on immune functions in mice and rats. Animals received 22 daily treatments of 0.03, 0.3, 3.0, or 30 mg PBB/kg body weight in a period covering 30 days. PBB exposure severely depressed cell mediated immunity in both mice and rats at the higher dosage levels as indicated by depressed responsiveness of splenic lymphocytes to mitogenic stimulation by polyclonal T-cell activators. Additionally, humoral immunity was depressed in mice at the 30.0 ppm dosage level. Assays for humoral immune functions included antibody production, serum immunoglobulin levels, and mitogenic stimulation of splenic lymphocytes to a polyclonal B-cell activator. These studies indicate that PBB exposure can lead to suppression of both humoral and particularly cell-mediated immune responses."}
{"id": "PMID:209981", "title": "Effect of polybrominated biphenyls on hepatic excretory function in rats and mice.", "content": "The purpose of this investigation was to determine the influence of polybrominated biphenyls (PBBs) on hepatic excretory function in developing and adult rats and mice. Prenatal or postnatal dietary exposure to PBBs (50 ppm in diet of pregnant or lactating mother or in diet of rat weanlings) resulted in elevated liver weight in developing rats. In 15-day-old rats that had been treated with PBBs increased liver weight correlated to enhanced ouabain transport from plasma into bile. Liver weight was also elevated in 21, 35, and 49-day-old rats exposed to PBBs, but this effect was not associated with stimulation of ouabain transport in these animals. However, adult rats fed 100 ppm PBBs for two weeks had significantly lower plasma concentrations of sulfobromophthalein (BSP) and increased biliary excretion of BSP, when compared to controls. PBBs-fed adult rats also excreted a greater percentage conjugated BSP (BSP-GSH) into bile. Two week dietary treatment of 100, 150, and 200 ppm PBBs resulted in enhanced initial disappearance of indocyanine green (ICG) from plasma of adult mice. However, dietary doses of 100 and 200 ppm PBBs to adult mice was not associated with enhanced capacity for ouabain excretion. In contrast, treatment with PBBs through the mother's diet (50 ppm) resulted in an almost twofold increase in cumulative ouabain excretion in 15-day-old mice. The results suggest that PBBs stimulate hepatic drug elimination in rats and mice, but the magnitude of the effect is dependent on age and transported compound.", "contents": "Effect of polybrominated biphenyls on hepatic excretory function in rats and mice. The purpose of this investigation was to determine the influence of polybrominated biphenyls (PBBs) on hepatic excretory function in developing and adult rats and mice. Prenatal or postnatal dietary exposure to PBBs (50 ppm in diet of pregnant or lactating mother or in diet of rat weanlings) resulted in elevated liver weight in developing rats. In 15-day-old rats that had been treated with PBBs increased liver weight correlated to enhanced ouabain transport from plasma into bile. Liver weight was also elevated in 21, 35, and 49-day-old rats exposed to PBBs, but this effect was not associated with stimulation of ouabain transport in these animals. However, adult rats fed 100 ppm PBBs for two weeks had significantly lower plasma concentrations of sulfobromophthalein (BSP) and increased biliary excretion of BSP, when compared to controls. PBBs-fed adult rats also excreted a greater percentage conjugated BSP (BSP-GSH) into bile. Two week dietary treatment of 100, 150, and 200 ppm PBBs resulted in enhanced initial disappearance of indocyanine green (ICG) from plasma of adult mice. However, dietary doses of 100 and 200 ppm PBBs to adult mice was not associated with enhanced capacity for ouabain excretion. In contrast, treatment with PBBs through the mother's diet (50 ppm) resulted in an almost twofold increase in cumulative ouabain excretion in 15-day-old mice. The results suggest that PBBs stimulate hepatic drug elimination in rats and mice, but the magnitude of the effect is dependent on age and transported compound."}
{"id": "PMID:209982", "title": "Potentiation of hepatic and renal toxicity of various compounds by prior exposure to polybrominated biphenyls.", "content": "Mice ingesting a standard rodent diet supplemented with polybrominated biphenyls (PBBs) were more susceptible to chlorinated hydrocarbon solvent-induced renal and hepatic damage, as well as the lethal effects of CHCl3 and CCl4, than were mice consuming control diet. As little as 0.025 ml/kg CHCl3 caused a significant increase in serum glutamic oxaloacetic transaminase (SGOT) and blood urea nitrogen (BUN) and a significant decrease in renal cortical slices accumulation of p-aminohippurate (PAH) in PBB-pretreated but not control mice. SGOT and serum glutamic pyruvate transaminase (SGPT) were greater in PBB-pretreated mice than in control mice after 0.125 and 0.005 ml/kg CCl4, respectively. Renal cortical PAH accumulation was greatly reduced in PBB-pretreated but not control mice aftter 0.125 ml/kg CCl4. The solvent-induced decrease in PAH accumulation was also greater in PBB-pretreated mice than in control mice following administration of 1.0 ml/kg trichloroethylene (TRI) and 0.15 ml/kg 1,1,2-trichloroethane (TCE).", "contents": "Potentiation of hepatic and renal toxicity of various compounds by prior exposure to polybrominated biphenyls. Mice ingesting a standard rodent diet supplemented with polybrominated biphenyls (PBBs) were more susceptible to chlorinated hydrocarbon solvent-induced renal and hepatic damage, as well as the lethal effects of CHCl3 and CCl4, than were mice consuming control diet. As little as 0.025 ml/kg CHCl3 caused a significant increase in serum glutamic oxaloacetic transaminase (SGOT) and blood urea nitrogen (BUN) and a significant decrease in renal cortical slices accumulation of p-aminohippurate (PAH) in PBB-pretreated but not control mice. SGOT and serum glutamic pyruvate transaminase (SGPT) were greater in PBB-pretreated mice than in control mice after 0.125 and 0.005 ml/kg CCl4, respectively. Renal cortical PAH accumulation was greatly reduced in PBB-pretreated but not control mice aftter 0.125 ml/kg CCl4. The solvent-induced decrease in PAH accumulation was also greater in PBB-pretreated mice than in control mice following administration of 1.0 ml/kg trichloroethylene (TRI) and 0.15 ml/kg 1,1,2-trichloroethane (TCE)."}
{"id": "PMID:209983", "title": "PBB fed to immature chickens: its effect on organ weights and function and on the cardiovascular system.", "content": "In a series of polybrominated biphenyl (PBB) feeding trials in White Leghorn cockerel chicks, the effects of PBB on various physiological parameters and organ weights were determined. These measurements included: growth, thyroid function, ECG, cardiac output, blood pressure, hematocrit, erythropoietin levels, and spleen, bursa of Fabricius, thyroid, testes, comb, liver weights. In addition, tissues were histologically examined. PBB, in the commercial grade form of hexabromobiphenyl, was administered continuously in the diet at levels ranging from 50 to 250 ppm. Pair-feeding studies were conducted to ascertain the effects of the drug per se since preliminary trials indicated that PBB administration resulted in decreased feed intake. Chronic administration resulted in depressed body weight as a result of decreased feed intake; decreased comb, testes, spleen, and bursa weights; increased liver and thyroid weight; hydropericardium and ascites; decreased hematological values due to depressed plasma erythropietin levels; decreased heart rate, packed cell volume, hemoglobin and cardiac output; decreased voltage amplitude of the ECG and a shift in the mean electrical axis. No significant differences were found in blood pressure (mean arterial and pulse pressure), stroke volume, or respiratory rate.", "contents": "PBB fed to immature chickens: its effect on organ weights and function and on the cardiovascular system. In a series of polybrominated biphenyl (PBB) feeding trials in White Leghorn cockerel chicks, the effects of PBB on various physiological parameters and organ weights were determined. These measurements included: growth, thyroid function, ECG, cardiac output, blood pressure, hematocrit, erythropoietin levels, and spleen, bursa of Fabricius, thyroid, testes, comb, liver weights. In addition, tissues were histologically examined. PBB, in the commercial grade form of hexabromobiphenyl, was administered continuously in the diet at levels ranging from 50 to 250 ppm. Pair-feeding studies were conducted to ascertain the effects of the drug per se since preliminary trials indicated that PBB administration resulted in decreased feed intake. Chronic administration resulted in depressed body weight as a result of decreased feed intake; decreased comb, testes, spleen, and bursa weights; increased liver and thyroid weight; hydropericardium and ascites; decreased hematological values due to depressed plasma erythropietin levels; decreased heart rate, packed cell volume, hemoglobin and cardiac output; decreased voltage amplitude of the ECG and a shift in the mean electrical axis. No significant differences were found in blood pressure (mean arterial and pulse pressure), stroke volume, or respiratory rate."}
{"id": "PMID:209984", "title": "Behavioral and neurological toxicity of polybrominated biphenyls in rats and mice.", "content": "Male, albino rats of the F-344/N strain and mice of the B6C3F1 strain were dosed by gavage, 5 days per week for a toal of 22 doses with 0.03--30 mg/kg of FireMaster FF-1, 0.168-16.8 Mg/kg of 2,4,5,2',4',5'-hexabromobiphenyl (HBB), or corn oil vehicle. A battery of tests was administered at the end of repeated dosing (30 day examination) and 30 days after dosing ceased (60 day test). FF-1 and, to a much lesser extent, HBB decreased body weight and performance on a variety of tests designed to detect neuromuscular dysfunction. Included in these tests were activity in the open field, forelimb grip strength, and muscular reflexes. Visual placement responses were also decreased in some animals, while hypothermia was observed in others. Emotionally, as measured by the number of defecations and urinations in the open field, was not affected by exposure to either compound. At the end of 30 day test, mice were less affected by exposure to these polybrominated biphenyls (PBBs) than rats; rats tended to worsen during the 30 days of no dosing, while mice tended to improve. These experiments indicate that oral dosing with levels of PBBs below those required to produce signs of acute toxicity produced behavioral or neurological toxicity when given repeatedly.", "contents": "Behavioral and neurological toxicity of polybrominated biphenyls in rats and mice. Male, albino rats of the F-344/N strain and mice of the B6C3F1 strain were dosed by gavage, 5 days per week for a toal of 22 doses with 0.03--30 mg/kg of FireMaster FF-1, 0.168-16.8 Mg/kg of 2,4,5,2',4',5'-hexabromobiphenyl (HBB), or corn oil vehicle. A battery of tests was administered at the end of repeated dosing (30 day examination) and 30 days after dosing ceased (60 day test). FF-1 and, to a much lesser extent, HBB decreased body weight and performance on a variety of tests designed to detect neuromuscular dysfunction. Included in these tests were activity in the open field, forelimb grip strength, and muscular reflexes. Visual placement responses were also decreased in some animals, while hypothermia was observed in others. Emotionally, as measured by the number of defecations and urinations in the open field, was not affected by exposure to either compound. At the end of 30 day test, mice were less affected by exposure to these polybrominated biphenyls (PBBs) than rats; rats tended to worsen during the 30 days of no dosing, while mice tended to improve. These experiments indicate that oral dosing with levels of PBBs below those required to produce signs of acute toxicity produced behavioral or neurological toxicity when given repeatedly."}
{"id": "PMID:209985", "title": "Persistent liver lesions in rats after a single oral dose of polybrominated biphenyls (firemaster FF-1) and concomitant PBB tissue levels.", "content": "In a preliminary study, 12 male and 12 female weanling Sherman strain rats were given a single dose of 1000 mg polybrominated biphenyls (PBBs) FireMaster FF1 Lot 7042 kg/body weight as a 5% solution in corn oil. Three male and three female weanling rats were given corn oil. One day after dosing PBB blood levels ranged from 78 to 162 ppm and 42 days later they ranged from 1.1 to 2.99 ppm. The liver was the only organ with pathological changes. In a long-term recovery study groups of 20 male and female rats, 2 months old, were given 0 or 1000 mg PBBs/kg body weight as a single dose in peanut oil. Five rats per group killed 2, 6, 10, and 14 months after dosing had pronounced liver pathology, including hepatic porphyria in the female rats and neoplastic nodules also mainly in female rats. Chemical analyses of blood, liver, and adipose tissue for PPBs 10 and 14 months after dosing gave the following mean results. Blood levels in females were 2.9 and 2.92 ppm, respectively, and males 0.94 and 1.34 ppm, respectively. Adipose tissue levels in females were 1202 and 783 ppm and in males 713 and 866 ppm, respectively. The liver levels in females were 37 and 22 ppm and in males 60 and 63 ppm, respectively.", "contents": "Persistent liver lesions in rats after a single oral dose of polybrominated biphenyls (firemaster FF-1) and concomitant PBB tissue levels. In a preliminary study, 12 male and 12 female weanling Sherman strain rats were given a single dose of 1000 mg polybrominated biphenyls (PBBs) FireMaster FF1 Lot 7042 kg/body weight as a 5% solution in corn oil. Three male and three female weanling rats were given corn oil. One day after dosing PBB blood levels ranged from 78 to 162 ppm and 42 days later they ranged from 1.1 to 2.99 ppm. The liver was the only organ with pathological changes. In a long-term recovery study groups of 20 male and female rats, 2 months old, were given 0 or 1000 mg PBBs/kg body weight as a single dose in peanut oil. Five rats per group killed 2, 6, 10, and 14 months after dosing had pronounced liver pathology, including hepatic porphyria in the female rats and neoplastic nodules also mainly in female rats. Chemical analyses of blood, liver, and adipose tissue for PPBs 10 and 14 months after dosing gave the following mean results. Blood levels in females were 2.9 and 2.92 ppm, respectively, and males 0.94 and 1.34 ppm, respectively. Adipose tissue levels in females were 1202 and 783 ppm and in males 713 and 866 ppm, respectively. The liver levels in females were 37 and 22 ppm and in males 60 and 63 ppm, respectively."}
{"id": "PMID:209986", "title": "Environmental considerations for the disposal of PBB-contaminated animals and wastes.", "content": "Accidental contamination of livestock feed in 1973 by polybrominated biphenyls (PBB) led to the destruction of over 30,000 animals in Michigan. Animal carcasses of mostly dairy cattle along with some beef cattle, hogs, sheep and rabbits destroyed under the Federal Food and Drug Administration guidelines were disposed on the land at an environmentally safe site in Kalkaska County, Michigan. The geology and hydrology of the disposal site on state-owned land is considered favorable for the disposal of contaminated carcasses and to prevent any migration of PBBs into ground and surface waters of the area. Materials underneath the site are predominantly sand with layers of silts and clays of glacial origin. The vertical isolation from the surface to the water table is over 90 ft, and the horizontal isolation to the privately owned properties and surface water bodies is well over 1.5 mile in all directions. The site design provides necessary safeguards for minimizing surface water infiltration into disposal trenches and maximizing the protection to the environment. A series of water wells in the direction of flow are established for monitoring groundwater quality for years to come. A 40-acre Gratiot County landfill located near St. Louis, Michigan, has received 269,000 lb of wastes containing 60 to 70% PBBs between 1971 and 1973. PBB wastes are intermixed with general refuse at various depths predominantly in the eastern half of the landfill. Phase I of the hydrogeological investigation shows that the landfill is situated immediately above the groundwater aquifer and a divide. Recently drilled test wells show traces of PBBs in the aquifer in all directions. Additional studies are planned in the near future for corrective measures and monitoring.", "contents": "Environmental considerations for the disposal of PBB-contaminated animals and wastes. Accidental contamination of livestock feed in 1973 by polybrominated biphenyls (PBB) led to the destruction of over 30,000 animals in Michigan. Animal carcasses of mostly dairy cattle along with some beef cattle, hogs, sheep and rabbits destroyed under the Federal Food and Drug Administration guidelines were disposed on the land at an environmentally safe site in Kalkaska County, Michigan. The geology and hydrology of the disposal site on state-owned land is considered favorable for the disposal of contaminated carcasses and to prevent any migration of PBBs into ground and surface waters of the area. Materials underneath the site are predominantly sand with layers of silts and clays of glacial origin. The vertical isolation from the surface to the water table is over 90 ft, and the horizontal isolation to the privately owned properties and surface water bodies is well over 1.5 mile in all directions. The site design provides necessary safeguards for minimizing surface water infiltration into disposal trenches and maximizing the protection to the environment. A series of water wells in the direction of flow are established for monitoring groundwater quality for years to come. A 40-acre Gratiot County landfill located near St. Louis, Michigan, has received 269,000 lb of wastes containing 60 to 70% PBBs between 1971 and 1973. PBB wastes are intermixed with general refuse at various depths predominantly in the eastern half of the landfill. Phase I of the hydrogeological investigation shows that the landfill is situated immediately above the groundwater aquifer and a divide. Recently drilled test wells show traces of PBBs in the aquifer in all directions. Additional studies are planned in the near future for corrective measures and monitoring."}
{"id": "PMID:209987", "title": "EM changes and other toxic effects of firemaster BP-6 (polybrominated biphenyls) in the mouse.", "content": "Groups of Swiss ICR mice were fed 1000 ppm polybrominated biphenyls (FireMaster BP-6) in rodent chow for 4, 8, 11, and 14 days. Control groups were fed standard rodent chow without FireMaster BP-6. Animals were killed at the end of each feeding period and the livers examined by electron microscopy. EM changes noted were progressive increase in size of hepatocytes, a decrease in rough endoplasmic reticulum, a marked increase in smooth endoplasmic reticulum, mitochondrial degeneration, increased lysosomes, and a decrease in glycogen. In addition, there was increasing proliferation of microvilli in bile canaliculi with increasing feeding times. A group of mice fed 1000 ppm FireMaster BP-6 in rodent chow for 11 days had livers with a mean of 13.93% of total body weight as compared with 6.49% for the control group (P=0.02). Tissue distribution following ingestion of 100 ppm FireMaster BP-6 for 14 days was studied. Twelve weeks post-feeding, the tissue concentrations of hexabromobiphenyl in order of highest concentration to lowest were as follows: perithymic fat, perirenal fat, adrenal glands, thymus gland, liver and stomach.", "contents": "EM changes and other toxic effects of firemaster BP-6 (polybrominated biphenyls) in the mouse. Groups of Swiss ICR mice were fed 1000 ppm polybrominated biphenyls (FireMaster BP-6) in rodent chow for 4, 8, 11, and 14 days. Control groups were fed standard rodent chow without FireMaster BP-6. Animals were killed at the end of each feeding period and the livers examined by electron microscopy. EM changes noted were progressive increase in size of hepatocytes, a decrease in rough endoplasmic reticulum, a marked increase in smooth endoplasmic reticulum, mitochondrial degeneration, increased lysosomes, and a decrease in glycogen. In addition, there was increasing proliferation of microvilli in bile canaliculi with increasing feeding times. A group of mice fed 1000 ppm FireMaster BP-6 in rodent chow for 11 days had livers with a mean of 13.93% of total body weight as compared with 6.49% for the control group (P=0.02). Tissue distribution following ingestion of 100 ppm FireMaster BP-6 for 14 days was studied. Twelve weeks post-feeding, the tissue concentrations of hexabromobiphenyl in order of highest concentration to lowest were as follows: perithymic fat, perirenal fat, adrenal glands, thymus gland, liver and stomach."}
{"id": "PMID:209988", "title": "PBB fed to adult female chickens: its effect on egg production, reproduction, viability of offspring, and residues in tissues and eggs.", "content": "Two experiments with light breed laying chickens fed polybrominated biphenyl (PBB) as FireMaster FF-1. The first involved feeding PBB at dietary levels of 0.2, 1, 5, 25, 125, 625, and 3125 ppm, the second involved levels of 30, 45, 60, 90, and 120. Each group had 24 hens, and each experiment had a control group of 24 hens. PBB diets were fed for 5 weeks. Feed intake, production, reproduction, tissue residues and viability of offspring were monitored during that time and a subsequent 8 weeks. Production, hatchability, and viability of offspring were significantly affected by feeding PBB at 45 ppm. Marked inanition occurred at levels of 625 and 3125 ppm, and there was some loss of feed intake at 125 ppm. There was a return to normal production and hatchability in 3 to 4 weeks after PBB withdrawal of diets with levels of 125 ppm or less. Dose--response lines are presented for PBB in muscle, liver, kidney, adipose tissue, and eggs. Withdrawal curves for PBB from these tissues are also given.", "contents": "PBB fed to adult female chickens: its effect on egg production, reproduction, viability of offspring, and residues in tissues and eggs. Two experiments with light breed laying chickens fed polybrominated biphenyl (PBB) as FireMaster FF-1. The first involved feeding PBB at dietary levels of 0.2, 1, 5, 25, 125, 625, and 3125 ppm, the second involved levels of 30, 45, 60, 90, and 120. Each group had 24 hens, and each experiment had a control group of 24 hens. PBB diets were fed for 5 weeks. Feed intake, production, reproduction, tissue residues and viability of offspring were monitored during that time and a subsequent 8 weeks. Production, hatchability, and viability of offspring were significantly affected by feeding PBB at 45 ppm. Marked inanition occurred at levels of 625 and 3125 ppm, and there was some loss of feed intake at 125 ppm. There was a return to normal production and hatchability in 3 to 4 weeks after PBB withdrawal of diets with levels of 125 ppm or less. Dose--response lines are presented for PBB in muscle, liver, kidney, adipose tissue, and eggs. Withdrawal curves for PBB from these tissues are also given."}
{"id": "PMID:209989", "title": "Pediatric health aspects of PBBs.", "content": "Many Michigan farm children are viewed as having suffered a deterioration in health coincident with contamination of dairy cattle by PBBs. Among Wisconsin dairy farm children such a deterioration was a rare event. There is a suggestion that Michigan farm children who had multiple symptoms during the 1973-76 period are getting better. A discrete syndrome of ill health has not been identified among Michigan farm children. The symptoms complained of indicate a disruption of various physiological functions, including neurobehavioral, gastrointestinal and immunological. Children from quarantined farms do not have a higher prevalence of multiple symptoms than those from nonquarantined farms.", "contents": "Pediatric health aspects of PBBs. Many Michigan farm children are viewed as having suffered a deterioration in health coincident with contamination of dairy cattle by PBBs. Among Wisconsin dairy farm children such a deterioration was a rare event. There is a suggestion that Michigan farm children who had multiple symptoms during the 1973-76 period are getting better. A discrete syndrome of ill health has not been identified among Michigan farm children. The symptoms complained of indicate a disruption of various physiological functions, including neurobehavioral, gastrointestinal and immunological. Children from quarantined farms do not have a higher prevalence of multiple symptoms than those from nonquarantined farms."}
{"id": "PMID:209990", "title": "Embryotoxic effects of polybrominated biphenyls (PBB) in rats.", "content": "Pregnant Sprague Dawley rats were given 0, 0.25, 0.5, 1, 5, and 10 mg of a commercial polybrominated biphenyl, FireMaster BP-6 (PBB), in olive oil by gavage each day from days 7 through 15 of pregnancy. Laboratory chow and water were given ad libitum. Treatment with PBB had no significant effect on body weight gain, food and water consumption, and urine production. The mothers were killed on day 20, and the only significant effect observed was an increased liver weight of those given 1, 5, and 10 mg PBB. Spleen, kidney, ovarian, gravid uterine, and perirenal fat pad weights were similar to those of control mothers. PBB had no significant effect on number of live/dead fetuses, crown-rump length or fetal weight. No grossly malformed fetuses were observed in PBB-treated mothers. The effects of PBB transfer from mothers to nursing pups was studied by reciprocal exchange of pups between control mothers and mothers treated with 10 mg PBB. When the pups were 21 days old, they were weaned and fed control chow. The following four combinations of prenatal-postnatal exposure were studied: control-control (C:C); control-PBB (C:PBB); PBB-control (PBB:C); and PBB-PBB. Although the birth weights of pups from PBB-treated mothers were similar to those of the controls, body weights of 60-day-old males exposed prenatally and postnatally (PBB:C, C:PBB, and PBB:PBB) were less (p less than 0.05) than those of the controls (C:C). The weights of the perirenal fat pads of male and female pups exposed to PBB were less (p less than 0.05) than the control. Liver weights, on a body weight basis, were higher in male and female pups exposed to PBB. Vaginal openings were delayed; the percentages of 36-day-old pups with open vaginas were 50 (C:C), 38 (PBB:C), 28 (C:PBB), and 30 (PBB:PBB).", "contents": "Embryotoxic effects of polybrominated biphenyls (PBB) in rats. Pregnant Sprague Dawley rats were given 0, 0.25, 0.5, 1, 5, and 10 mg of a commercial polybrominated biphenyl, FireMaster BP-6 (PBB), in olive oil by gavage each day from days 7 through 15 of pregnancy. Laboratory chow and water were given ad libitum. Treatment with PBB had no significant effect on body weight gain, food and water consumption, and urine production. The mothers were killed on day 20, and the only significant effect observed was an increased liver weight of those given 1, 5, and 10 mg PBB. Spleen, kidney, ovarian, gravid uterine, and perirenal fat pad weights were similar to those of control mothers. PBB had no significant effect on number of live/dead fetuses, crown-rump length or fetal weight. No grossly malformed fetuses were observed in PBB-treated mothers. The effects of PBB transfer from mothers to nursing pups was studied by reciprocal exchange of pups between control mothers and mothers treated with 10 mg PBB. When the pups were 21 days old, they were weaned and fed control chow. The following four combinations of prenatal-postnatal exposure were studied: control-control (C:C); control-PBB (C:PBB); PBB-control (PBB:C); and PBB-PBB. Although the birth weights of pups from PBB-treated mothers were similar to those of the controls, body weights of 60-day-old males exposed prenatally and postnatally (PBB:C, C:PBB, and PBB:PBB) were less (p less than 0.05) than those of the controls (C:C). The weights of the perirenal fat pads of male and female pups exposed to PBB were less (p less than 0.05) than the control. Liver weights, on a body weight basis, were higher in male and female pups exposed to PBB. Vaginal openings were delayed; the percentages of 36-day-old pups with open vaginas were 50 (C:C), 38 (PBB:C), 28 (C:PBB), and 30 (PBB:PBB)."}
{"id": "PMID:209991", "title": "Characteristics of cytochrome P-450 and mixed function oxidase enzymes following treatment with PBBs.", "content": "The mixture of PBBs in FireMaster BP-6 has been demonstrated to constitute potent inducers of hepatic and extrahepatic mixed function oxidase (MFO) enzymes. Chronic dietary administration of PBBs to mature female rats results in a \"mixed\" pattern of induction, with increases in both cytochrome P-450 and P1-450 associated enzymes. Acute administration of PBBs (150 mg/kg IP) to mature female rats resulted in a time-dependent induction of MFO activities; the P-450-dependent enzymes were simulated early (24-48 hr after administration) while the P1-450 dependent enzymes reached maximal activities at later time points. However, studies of the kinetics and patterns of inhibition of the induced enzymes along with gel electrophoresis studies of the microsomal proteins indicate that PBBs may induce different proteins from those induced by the classical P-450 and P1-450 inducers, phenobarbital and 3-methylcholanthrene. In addition, the pattern of enzyme induction caused by PBBs in developing rats differs from that in adults, in that the P1-450-associated enzymes are stimulated prior to the P-450-associated enzymes. The overall pattern of enzyme induction in extrahepatic tissue differs from that seen in the liver and sex differences in enzyme induction have also been demonstrated. As modifications of MFO activity may alter the toxicity of chemicals, these findings suggest that the toxicity of chemicals may be altered in animals exposed to PBBs and that these toxicities may exhibit age, sex, and organ specificities different from those seen in control animals.", "contents": "Characteristics of cytochrome P-450 and mixed function oxidase enzymes following treatment with PBBs. The mixture of PBBs in FireMaster BP-6 has been demonstrated to constitute potent inducers of hepatic and extrahepatic mixed function oxidase (MFO) enzymes. Chronic dietary administration of PBBs to mature female rats results in a \"mixed\" pattern of induction, with increases in both cytochrome P-450 and P1-450 associated enzymes. Acute administration of PBBs (150 mg/kg IP) to mature female rats resulted in a time-dependent induction of MFO activities; the P-450-dependent enzymes were simulated early (24-48 hr after administration) while the P1-450 dependent enzymes reached maximal activities at later time points. However, studies of the kinetics and patterns of inhibition of the induced enzymes along with gel electrophoresis studies of the microsomal proteins indicate that PBBs may induce different proteins from those induced by the classical P-450 and P1-450 inducers, phenobarbital and 3-methylcholanthrene. In addition, the pattern of enzyme induction caused by PBBs in developing rats differs from that in adults, in that the P1-450-associated enzymes are stimulated prior to the P-450-associated enzymes. The overall pattern of enzyme induction in extrahepatic tissue differs from that seen in the liver and sex differences in enzyme induction have also been demonstrated. As modifications of MFO activity may alter the toxicity of chemicals, these findings suggest that the toxicity of chemicals may be altered in animals exposed to PBBs and that these toxicities may exhibit age, sex, and organ specificities different from those seen in control animals."}
{"id": "PMID:209992", "title": "Induction of monooxygenation in rainbow trout by polybrominated biphenyls: a comparative study.", "content": "Two commercial polychlorinated biphenyl mixtures (Aroclor 1254 and Aroclor 1242) and one polybrominated biphenyl mixture (FireMaster BP-6) were examined for their abilities to induce hepatic microsomal monooxygenation in rainbow trout (Salmo gairdneri). Pretreatment of rainbow trout with Aroclors 1254 and 1242 (150 mg/kg IP) resulted in an approximate 10-fold induction of arylhydrocarbon (benzo[a]pyrene) hydroxylation, ethoxycoumarin-O-deethylation and ethoxyresorufin-O-deethylation within 7 days after injection. These enzyme activities remained elevated above control values for at least 2-3 weeks. Administration of FireMaster BP-6 (150 mg/kg IP) also resulted in an induction of several monooxygenase activities. Arylhydrocarbon (benzo[a]pyrene) hydroxylation, ethoxycoumarin-O-deethylation and ethoxyresorufin-O-deethylation were increased by 6-, 3,- and 25-fold, respectively. Only the latter two activities remained elevated two weeks post-injection. Ethylmorphine-N-demethylation was unaffected by the polyhalogenated biphenyls. Significant increases in P-450 hemoprotein were not observed after pretreatment with any of the polyhalogenated biphenyls studied.", "contents": "Induction of monooxygenation in rainbow trout by polybrominated biphenyls: a comparative study. Two commercial polychlorinated biphenyl mixtures (Aroclor 1254 and Aroclor 1242) and one polybrominated biphenyl mixture (FireMaster BP-6) were examined for their abilities to induce hepatic microsomal monooxygenation in rainbow trout (Salmo gairdneri). Pretreatment of rainbow trout with Aroclors 1254 and 1242 (150 mg/kg IP) resulted in an approximate 10-fold induction of arylhydrocarbon (benzo[a]pyrene) hydroxylation, ethoxycoumarin-O-deethylation and ethoxyresorufin-O-deethylation within 7 days after injection. These enzyme activities remained elevated above control values for at least 2-3 weeks. Administration of FireMaster BP-6 (150 mg/kg IP) also resulted in an induction of several monooxygenase activities. Arylhydrocarbon (benzo[a]pyrene) hydroxylation, ethoxycoumarin-O-deethylation and ethoxyresorufin-O-deethylation were increased by 6-, 3,- and 25-fold, respectively. Only the latter two activities remained elevated two weeks post-injection. Ethylmorphine-N-demethylation was unaffected by the polyhalogenated biphenyls. Significant increases in P-450 hemoprotein were not observed after pretreatment with any of the polyhalogenated biphenyls studied."}
{"id": "PMID:209993", "title": "Family clustering of PBB and DDE values among Michigan dairy farmers.", "content": "Family clustering of varying levels of serum PBB and DDE was evaluated for 62 Michigan families by using the mean and standard deviation for family units, ranked percentile comparison of family members, and correlation by linear regression of family members. The results indicate that levels of serum PBBs cluster within family units and for children within families. Serum DDE clustering within families occurs only for children. These findings are consistent with recent, interim PBB exposure, perhaps from a common dietary source for families. Serum DDE represents a lifetime, low-level exposure to DDT-DDE which has been both less prolonged and less intense for children. Thus similar levels, or clustered serum DDE, was observed for children within families.", "contents": "Family clustering of PBB and DDE values among Michigan dairy farmers. Family clustering of varying levels of serum PBB and DDE was evaluated for 62 Michigan families by using the mean and standard deviation for family units, ranked percentile comparison of family members, and correlation by linear regression of family members. The results indicate that levels of serum PBBs cluster within family units and for children within families. Serum DDE clustering within families occurs only for children. These findings are consistent with recent, interim PBB exposure, perhaps from a common dietary source for families. Serum DDE represents a lifetime, low-level exposure to DDT-DDE which has been both less prolonged and less intense for children. Thus similar levels, or clustered serum DDE, was observed for children within families."}
{"id": "PMID:209994", "title": "Toxicity of firemaster FF-1 and 2,2',4,4',5,5'-hexabromobiphenyl in cultures of C3H/10T 1/2 mammalian fibroblasts.", "content": "A procedure for purifying 2,2', 4,4',5,5'-hexabromobiphenyl (HBB) from FireMaster FF-1 in gram amounts by crystallization is presented. Following purification, the structural assignment of HBB was made by using proton and carbon-13 nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, and mass spectroscopy (MS). The growth of C3H/10T 1/2 cells treated with 5, 37, 75, and 150 microgram of HBB and FF-1 per milliliter of medium was measured at 4, 8, and 13 days following treatment. FF-1 was more toxic at 37 and 75 microgram/ml at both 4 and 8 days, but the same at 13 days. At 150 microgram/ml cell growth was completely inhibited by both compounds. Growth of cells was stimulated at 5 microgram/ml, by HBB at 4 and 8 days, and FF-1 at 8 and 12 days. HCB was compared with HBB and FF-1 for cell growth toxicity at 37 and 75 microgram/ml. At 75 microgram/ml, HCB was more toxic than HBB and FF-1 during the entire time period. At 37 microgram/ml, HCB was more toxic than HBB and FF-1 at 4 and 8 days. Cells seeded at high densities and treated with HBB for three days lost the high degree of postconfluence inhibition of cell division observed in control cultures. Cells treated with FF-1 for three days did not adhere well to the plastic growth surface. Ultrastructural features of the HBB- and FF-1-treated cells included decreased surface villi and increased lysosomes relative to the control cells.", "contents": "Toxicity of firemaster FF-1 and 2,2',4,4',5,5'-hexabromobiphenyl in cultures of C3H/10T 1/2 mammalian fibroblasts. A procedure for purifying 2,2', 4,4',5,5'-hexabromobiphenyl (HBB) from FireMaster FF-1 in gram amounts by crystallization is presented. Following purification, the structural assignment of HBB was made by using proton and carbon-13 nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, and mass spectroscopy (MS). The growth of C3H/10T 1/2 cells treated with 5, 37, 75, and 150 microgram of HBB and FF-1 per milliliter of medium was measured at 4, 8, and 13 days following treatment. FF-1 was more toxic at 37 and 75 microgram/ml at both 4 and 8 days, but the same at 13 days. At 150 microgram/ml cell growth was completely inhibited by both compounds. Growth of cells was stimulated at 5 microgram/ml, by HBB at 4 and 8 days, and FF-1 at 8 and 12 days. HCB was compared with HBB and FF-1 for cell growth toxicity at 37 and 75 microgram/ml. At 75 microgram/ml, HCB was more toxic than HBB and FF-1 during the entire time period. At 37 microgram/ml, HCB was more toxic than HBB and FF-1 at 4 and 8 days. Cells seeded at high densities and treated with HBB for three days lost the high degree of postconfluence inhibition of cell division observed in control cultures. Cells treated with FF-1 for three days did not adhere well to the plastic growth surface. Ultrastructural features of the HBB- and FF-1-treated cells included decreased surface villi and increased lysosomes relative to the control cells."}
{"id": "PMID:209995", "title": "Effect of polybrominated biphenyls on adenylate cyclase activity in rat lung alveoli.", "content": "The in vitro effect of polybrominated biphenyls (FireMaster BP-6) on adenylate cyclase [ATP pyrophosphate lyase (cyclizing), EC 4.6.1.1] activity in plasma membranes of rat lung alveoli was determined. Two fractions of plasma membranes, PM-I (approximate d = 1.13 g/cm3) and PM-II (approximate d = 1.16 g/cm3) were isolated under hypotonic homogenization and fractionation conditions (1mM NaHCO3, 5mM dithiothreitol, pH 7.5) by using differential centrifugation and nonlinear sucrose gradient centrifugation techniques. Polybrominated biphenyls (10 microgram/ml) dissolved in ethyl acetate (0.25%) stimulated basal adenylate cyclase activity of plasma membranes by 2.1 to 2.5-fold. The implication of this observation is discussed.", "contents": "Effect of polybrominated biphenyls on adenylate cyclase activity in rat lung alveoli. The in vitro effect of polybrominated biphenyls (FireMaster BP-6) on adenylate cyclase [ATP pyrophosphate lyase (cyclizing), EC 4.6.1.1] activity in plasma membranes of rat lung alveoli was determined. Two fractions of plasma membranes, PM-I (approximate d = 1.13 g/cm3) and PM-II (approximate d = 1.16 g/cm3) were isolated under hypotonic homogenization and fractionation conditions (1mM NaHCO3, 5mM dithiothreitol, pH 7.5) by using differential centrifugation and nonlinear sucrose gradient centrifugation techniques. Polybrominated biphenyls (10 microgram/ml) dissolved in ethyl acetate (0.25%) stimulated basal adenylate cyclase activity of plasma membranes by 2.1 to 2.5-fold. The implication of this observation is discussed."}
{"id": "PMID:209996", "title": "Liver function tests among Michigan and Wisconsin dairy farmers.", "content": "Serum activity of SGOT, SGPT, LDH, and alkaline phosphatase was measured in 614 Michigan adults exposed to PBB and 141 Wisconsin adults not so exposed. The Michigan group had higher prevalence of abnormal SGOT (p less than 0.005) and SGPT (p less than 0.005). A clear sex difference was observed. Michigan men had a higher prevalence of abnormal SGPT (p less than 0.005) and LDH (p less than 0.005) than Michigan women, and a higher prevalence than Wisconsin men of abnormal SGOT (p less than 0.005) and SGPT (p less than 0.01). These differences could not be ascribed to differing patterns of alcohol consumption, laboratory error, or choice of criteria for normality/abnormality. Seven Michigan subgroups were defined on the basis of the criteria by which they had been selected to participate. The two subgroups who were essentially self-invited did not differ from the remaining five randomly selected subgroups combined in prevalence of these abnormal liver function tests. Based on 364 serum PBB analyses thus far analyzed of the 614 Michigan participants, no obvious relationship between serum PBB values and liver function tests was observed. However, this is a tentative conclusion that will be further evaluated when remaining serum PBB analyses are completed. The greater prevalence of abnormal SGPT and SGOT among Michigan dairy farm residents compared to the Wisconsin dairy farm residents is tentatively ascribed to the former group's exposure to PBB.", "contents": "Liver function tests among Michigan and Wisconsin dairy farmers. Serum activity of SGOT, SGPT, LDH, and alkaline phosphatase was measured in 614 Michigan adults exposed to PBB and 141 Wisconsin adults not so exposed. The Michigan group had higher prevalence of abnormal SGOT (p less than 0.005) and SGPT (p less than 0.005). A clear sex difference was observed. Michigan men had a higher prevalence of abnormal SGPT (p less than 0.005) and LDH (p less than 0.005) than Michigan women, and a higher prevalence than Wisconsin men of abnormal SGOT (p less than 0.005) and SGPT (p less than 0.01). These differences could not be ascribed to differing patterns of alcohol consumption, laboratory error, or choice of criteria for normality/abnormality. Seven Michigan subgroups were defined on the basis of the criteria by which they had been selected to participate. The two subgroups who were essentially self-invited did not differ from the remaining five randomly selected subgroups combined in prevalence of these abnormal liver function tests. Based on 364 serum PBB analyses thus far analyzed of the 614 Michigan participants, no obvious relationship between serum PBB values and liver function tests was observed. However, this is a tentative conclusion that will be further evaluated when remaining serum PBB analyses are completed. The greater prevalence of abnormal SGPT and SGOT among Michigan dairy farm residents compared to the Wisconsin dairy farm residents is tentatively ascribed to the former group's exposure to PBB."}
{"id": "PMID:209997", "title": "Polybrominated biphenyl toxicosis in rats fed an iodine-deficient, iodine-adequate, or iodine-excess diet.", "content": "Young male Sprague-Dawley rats were fed 0, 1, 10, or 100 ppm of polybrominated biphenyls (PBB) in iodine-deficient, iodine-adequate (0.2 ppm), or iodine-excess (1000 ppm) diets. Six rats in each of the 12 groups were killed at 30 days and the remaining six in each group at 60 days. Growth rates were similar in all rats fed diets containing 0, 1, or 10 ppm PBB but were slower from 30 to 60 days in rats given 100 ppm PBB. Results of routine hematologic examinations and urinalyses were essentially normal. Although liver weights were substantially increased by PBB, the smallest increases were in rats fed an iodine-deficient diet. Thyroid weights were increased by iodine deficiency and by 10 and 100 ppm PBB. Electropherograms of serum proteins, serum lipoproteins, and LDH isozymes at 60 days from rats given PBB indicated hepatic alterations, but changes were least dramatic in rats fed an iodine-deficient diet plus PBB and most severe in rats fed iodine-excess diets plus PBB. Hepatic lesions were basically similar to those previously described except that bile duct proliferation was seen at 60 days only in rats fed an iodine-deficient diet and 100 ppm PBB. Histologic changes in thyroid glands were associated with iodine deficiency and with PBB. The iodine-excess diet plus 100 ppm PBB induced squamous metaplasia of respiratory bronchiolar epithelium. These results indicate interrelationships between PBB and iodine which may affect the toxicosis caused by PBB.", "contents": "Polybrominated biphenyl toxicosis in rats fed an iodine-deficient, iodine-adequate, or iodine-excess diet. Young male Sprague-Dawley rats were fed 0, 1, 10, or 100 ppm of polybrominated biphenyls (PBB) in iodine-deficient, iodine-adequate (0.2 ppm), or iodine-excess (1000 ppm) diets. Six rats in each of the 12 groups were killed at 30 days and the remaining six in each group at 60 days. Growth rates were similar in all rats fed diets containing 0, 1, or 10 ppm PBB but were slower from 30 to 60 days in rats given 100 ppm PBB. Results of routine hematologic examinations and urinalyses were essentially normal. Although liver weights were substantially increased by PBB, the smallest increases were in rats fed an iodine-deficient diet. Thyroid weights were increased by iodine deficiency and by 10 and 100 ppm PBB. Electropherograms of serum proteins, serum lipoproteins, and LDH isozymes at 60 days from rats given PBB indicated hepatic alterations, but changes were least dramatic in rats fed an iodine-deficient diet plus PBB and most severe in rats fed iodine-excess diets plus PBB. Hepatic lesions were basically similar to those previously described except that bile duct proliferation was seen at 60 days only in rats fed an iodine-deficient diet and 100 ppm PBB. Histologic changes in thyroid glands were associated with iodine deficiency and with PBB. The iodine-excess diet plus 100 ppm PBB induced squamous metaplasia of respiratory bronchiolar epithelium. These results indicate interrelationships between PBB and iodine which may affect the toxicosis caused by PBB."}
{"id": "PMID:209998", "title": "Formation of brominated dibenzofurans from pyrolysis of the polybrominated biphenyl fire retardant, firemaster FF-1.", "content": "The polybrominated biphenyl (PBB) fire retardant, FireMaster FF-1, was pyrolyzed for 20 min at 380-400 degrees C in open glass tubes and in tubes sealed after nitrogen flushing. The pyrolyzed residue was extracted with benzene, and extracts were cleaned up on columns of graphite (Carbopack A) and alumina. Analysis was carried out by low resolution direct probe mass spectrometry (MS). Spectra from extracts of the open tube pyrolyzed material had a series of ions characteristic of tetra- and pentabrominated dibenzofurans as evidenced by comparison with spectra from 2,3,7,8-tetrabromodibenzofuran (TBDF). Confirmatory evidence for the brominated dibenzofurans was obtained by high resolution MS dual ion analysis of certain fragment and molecular ions. Recovery values of TBDF through the cleanup procedure averaged 50% and, using this recovery value and TBDF as an external standard, dual ion analyses indicated that 40 ppm tetra- and 4 ppm pentabrominanted dibenzofuran were produced based on the PBB level used in the pyrolysis experiments. Additional analysis of the open tube pyrolyzed material by gas chromatography/mass spectrometry provided evidence that there was one tetrabromodibenzofuran compound with a retention time equal to that of TBDF. Trace levels (less than 1 ppm) of the molecular ion of tetrabrominated dibenzofuran were found after analysis by low resolution MS of the PBB pyrolyzed under nitrogen in sealed tubes. The experimental evidence is consistent with a mechanism for brominated dibenzofuran formation involving attack of oxygen on PBB compounds.", "contents": "Formation of brominated dibenzofurans from pyrolysis of the polybrominated biphenyl fire retardant, firemaster FF-1. The polybrominated biphenyl (PBB) fire retardant, FireMaster FF-1, was pyrolyzed for 20 min at 380-400 degrees C in open glass tubes and in tubes sealed after nitrogen flushing. The pyrolyzed residue was extracted with benzene, and extracts were cleaned up on columns of graphite (Carbopack A) and alumina. Analysis was carried out by low resolution direct probe mass spectrometry (MS). Spectra from extracts of the open tube pyrolyzed material had a series of ions characteristic of tetra- and pentabrominated dibenzofurans as evidenced by comparison with spectra from 2,3,7,8-tetrabromodibenzofuran (TBDF). Confirmatory evidence for the brominated dibenzofurans was obtained by high resolution MS dual ion analysis of certain fragment and molecular ions. Recovery values of TBDF through the cleanup procedure averaged 50% and, using this recovery value and TBDF as an external standard, dual ion analyses indicated that 40 ppm tetra- and 4 ppm pentabrominanted dibenzofuran were produced based on the PBB level used in the pyrolysis experiments. Additional analysis of the open tube pyrolyzed material by gas chromatography/mass spectrometry provided evidence that there was one tetrabromodibenzofuran compound with a retention time equal to that of TBDF. Trace levels (less than 1 ppm) of the molecular ion of tetrabrominated dibenzofuran were found after analysis by low resolution MS of the PBB pyrolyzed under nitrogen in sealed tubes. The experimental evidence is consistent with a mechanism for brominated dibenzofuran formation involving attack of oxygen on PBB compounds."}
{"id": "PMID:209999", "title": "Assessment of the hazards of polybrominated biphenyls.", "content": "During their peak use period, PBBs represented under 1% of the total sales of fire retardant chemicals, and very probably would have escaped intensive study if they had not been mixed accidentally with animal feed preparations. Instead, international attention was drawn to PBBs by the state-supervised killing of over 35,000 cattle which had been contaminated with PBBs. Interestingly, low doses of PBBs exert a broad spectrum of toxicological, pharmacological, and biochemical effects despite low acute toxicity. These effects and the intensive bioaccumulation of PBBs derive from their structure and their consequent resistance of biotransformation and high solubility in fat. In rodents, PBBs are teratogenic, immunosuppressive, and potentially carcinogenic. In bovine, rodent, and avian species, PBBs reduce feed intake and induce mixed function oxidases of liver microsomes. The latter effect may be responsible for steroid level changes which underline hormonal toxicities observed in cows, mink, rats, and chickens. The effects of PBBs on humans are controversial, but data suggestive of immunological, skin, and liver disorders continue to accumulate. Concern about the clinical effects of PBBs is heightened by the knowledge that these compounds readily enter the fetus by crossing the placental barrier and can be transferred to newborn children after extensive passage into breast milk.", "contents": "Assessment of the hazards of polybrominated biphenyls. During their peak use period, PBBs represented under 1% of the total sales of fire retardant chemicals, and very probably would have escaped intensive study if they had not been mixed accidentally with animal feed preparations. Instead, international attention was drawn to PBBs by the state-supervised killing of over 35,000 cattle which had been contaminated with PBBs. Interestingly, low doses of PBBs exert a broad spectrum of toxicological, pharmacological, and biochemical effects despite low acute toxicity. These effects and the intensive bioaccumulation of PBBs derive from their structure and their consequent resistance of biotransformation and high solubility in fat. In rodents, PBBs are teratogenic, immunosuppressive, and potentially carcinogenic. In bovine, rodent, and avian species, PBBs reduce feed intake and induce mixed function oxidases of liver microsomes. The latter effect may be responsible for steroid level changes which underline hormonal toxicities observed in cows, mink, rats, and chickens. The effects of PBBs on humans are controversial, but data suggestive of immunological, skin, and liver disorders continue to accumulate. Concern about the clinical effects of PBBs is heightened by the knowledge that these compounds readily enter the fetus by crossing the placental barrier and can be transferred to newborn children after extensive passage into breast milk."}
{"id": "PMID:210000", "title": "Effects of processing and cooking on PBB residues.", "content": "To study the effect of processing on polybrominated biphenyl (PBB) levels, milk from four dairy herds containing less than 0.3 ppm (fat basis) of physiologically incorporated PBBs was presented individually into cream, skim milk, butter, and stirred curd cheese. Pasteurized and freeze-dried whole milk, skim milk, and cream, spray-dried whole milk and skim milk, and condensed whole milk were also made. PBBs were concentrated in the high-fat products. Spray-drying reduced PBBs in whole milk and skim milk while pasteurization, freeze-drying, aging of cheese, and condensation were not effective. To study the effect of cooking on PBB levels, thigh meat, thigh skin, drumstick and breast (with skin) from half of chickens fed PBBs were analyzed raw, and pieces from the other halves were analysed following separate pressure cooking. The level of PBBs expressed as parts per million on a solids basis was lower in the cooked sample than in the corresponding raw piece and part of the PBBs lost were found in the drip. Recoveries of PBBs in cooked tissue and broth ranged from 68.1% in the thigh skin to 84.6% in the drumstick, with approximately two-thirds of the recovered PBBs found in the cooked meat itself. Therefore, pressure cooking resulted in a loss ranging from 36% for the drumstick to 53% for the thigh skin.", "contents": "Effects of processing and cooking on PBB residues. To study the effect of processing on polybrominated biphenyl (PBB) levels, milk from four dairy herds containing less than 0.3 ppm (fat basis) of physiologically incorporated PBBs was presented individually into cream, skim milk, butter, and stirred curd cheese. Pasteurized and freeze-dried whole milk, skim milk, and cream, spray-dried whole milk and skim milk, and condensed whole milk were also made. PBBs were concentrated in the high-fat products. Spray-drying reduced PBBs in whole milk and skim milk while pasteurization, freeze-drying, aging of cheese, and condensation were not effective. To study the effect of cooking on PBB levels, thigh meat, thigh skin, drumstick and breast (with skin) from half of chickens fed PBBs were analyzed raw, and pieces from the other halves were analysed following separate pressure cooking. The level of PBBs expressed as parts per million on a solids basis was lower in the cooked sample than in the corresponding raw piece and part of the PBBs lost were found in the drip. Recoveries of PBBs in cooked tissue and broth ranged from 68.1% in the thigh skin to 84.6% in the drumstick, with approximately two-thirds of the recovered PBBs found in the cooked meat itself. Therefore, pressure cooking resulted in a loss ranging from 36% for the drumstick to 53% for the thigh skin."}
{"id": "PMID:210001", "title": "Distribution and kinetics of PBB residues in cattle.", "content": "Cows fed a constant amount of polybrominated biphenyl (PBB) reached a steady-state concentration in milk fat within 30 days. This concentration was approximately four times the concentration in the total diet. When feeding of PBB was stopped, the concentration in milk was adequately described as a sum of two first-order elimination rates. Biological half-life in environmentally contaminated cows, studied for 6 months about a year after contamination, was 60 days. The stage of lactation affected the rate of elimination, and in some concentrations increased shortly after calving. Residues were distributed in body tissues proportionally to concentration of fat in the tissues. Liver and brain were exceptions. Concentration in liver fat was generally higher than other tissues and possibly related to the treatment of some cows with phenobarbital. Residues in brain fat were significantly lower than all other tissues. The ratio of the concentrations in milk fat to concentration of residues in the blood of calves and fat of fetal tissues to the concentration in the corresponding tissue in the dams was 0.36:1. It was estimated that people consuming milk from the highly contaminated Michigan cows could have received PBB doses as great as 10 g from this source alone.", "contents": "Distribution and kinetics of PBB residues in cattle. Cows fed a constant amount of polybrominated biphenyl (PBB) reached a steady-state concentration in milk fat within 30 days. This concentration was approximately four times the concentration in the total diet. When feeding of PBB was stopped, the concentration in milk was adequately described as a sum of two first-order elimination rates. Biological half-life in environmentally contaminated cows, studied for 6 months about a year after contamination, was 60 days. The stage of lactation affected the rate of elimination, and in some concentrations increased shortly after calving. Residues were distributed in body tissues proportionally to concentration of fat in the tissues. Liver and brain were exceptions. Concentration in liver fat was generally higher than other tissues and possibly related to the treatment of some cows with phenobarbital. Residues in brain fat were significantly lower than all other tissues. The ratio of the concentrations in milk fat to concentration of residues in the blood of calves and fat of fetal tissues to the concentration in the corresponding tissue in the dams was 0.36:1. It was estimated that people consuming milk from the highly contaminated Michigan cows could have received PBB doses as great as 10 g from this source alone."}
{"id": "PMID:210002", "title": "Distribution of polybrominated biphenyls after dietary exposure in pregnant and lactating rats and their offspring.", "content": "Female rats were fed PBBs in the diet (50 ppm) from day 8 of gestation to day 21 of gestation, from day 1 postpartum to day 14 postpartum or from day 8 of gestation through day 14 postpartum. Levels of PBBs were measured in various tissues. Small concentrations of PBBs (less than 5 microgram/g) were found in the brain, heart, lung, liver, small intestine, placenta, and gravid uterus. Larger concentrations (less than 30 microgram/g) were found in kidneys, the nongravid uterus, skin, mammary tissue, and fat. Lactation did not significantly alter the concentrations of PBBs found in tissues other than mammary tissue. Offspring were subjected to several exposure regimens by cross-fostering. Concentrations of PBBs in the neonatal livers were higher than in the adults nursing them. Transfer of PBBs via the milk appears to be much more important to appearance of PBBs in newborns than does placental transfer.", "contents": "Distribution of polybrominated biphenyls after dietary exposure in pregnant and lactating rats and their offspring. Female rats were fed PBBs in the diet (50 ppm) from day 8 of gestation to day 21 of gestation, from day 1 postpartum to day 14 postpartum or from day 8 of gestation through day 14 postpartum. Levels of PBBs were measured in various tissues. Small concentrations of PBBs (less than 5 microgram/g) were found in the brain, heart, lung, liver, small intestine, placenta, and gravid uterus. Larger concentrations (less than 30 microgram/g) were found in kidneys, the nongravid uterus, skin, mammary tissue, and fat. Lactation did not significantly alter the concentrations of PBBs found in tissues other than mammary tissue. Offspring were subjected to several exposure regimens by cross-fostering. Concentrations of PBBs in the neonatal livers were higher than in the adults nursing them. Transfer of PBBs via the milk appears to be much more important to appearance of PBBs in newborns than does placental transfer."}
{"id": "PMID:210003", "title": "Effects of PBBs on cattle. IV. Distribution and clearance of components of firemaster BP-6.", "content": "Sixty dairy animals were utilized in seven experiments to determine aspects of the distribution and clearance of FireMaster BP-6. Experimental protocols of various studies provided daily exposures from 0.25 to 25,000 mg, exposures for 1 to 202 days, and total study periods from 10 to 1100 days. Necropsy of 28 animals provided information on residue concentrations in 35 tissues, and the excretion in milk was determined in 15 animals. These studies showed that the major brominated biphenyls of this commercial mixture were absorbed from the gastrointestinal tract and appeared in the blood plasma within 4 hr. With continued exposure to the residue plasma concentrations reached a steady state by 15 days. Free PBB was not detectable in urine. During PBB feeding feces was the major route of excretion, representing approximately 50% of the amount fed to animals not displaying signs of toxicosis. Following a withdrawal of PBB, fecal concentrations declined to 1 to 2% of concentrations during dosing, yet, feces remained the major excretory route in nonlactating animals. In contrast, in post-exposure lactating animals milk fat became an important excretory route removing three-times the quantity of residue cleared in feces. Following parturition, concentrations of PBB in milk fat declined approximately twofold in 6 days. Thereafter, the residue concentration in milk fat was approximately 0.4 that in depot fats. PBB had a predilection for lipid tissues with similar concentrations in various depot fats. Concentrations of the residue were notably low in tissues of the nervous system despite the high content of lipid material. Liver contained residue concentrations that were disproportionately high when compared to the lipid content of the organ. Calves born to PBB-exposed cows had similar distribution of residues in body tissues although concentrations were less than those of the dam.", "contents": "Effects of PBBs on cattle. IV. Distribution and clearance of components of firemaster BP-6. Sixty dairy animals were utilized in seven experiments to determine aspects of the distribution and clearance of FireMaster BP-6. Experimental protocols of various studies provided daily exposures from 0.25 to 25,000 mg, exposures for 1 to 202 days, and total study periods from 10 to 1100 days. Necropsy of 28 animals provided information on residue concentrations in 35 tissues, and the excretion in milk was determined in 15 animals. These studies showed that the major brominated biphenyls of this commercial mixture were absorbed from the gastrointestinal tract and appeared in the blood plasma within 4 hr. With continued exposure to the residue plasma concentrations reached a steady state by 15 days. Free PBB was not detectable in urine. During PBB feeding feces was the major route of excretion, representing approximately 50% of the amount fed to animals not displaying signs of toxicosis. Following a withdrawal of PBB, fecal concentrations declined to 1 to 2% of concentrations during dosing, yet, feces remained the major excretory route in nonlactating animals. In contrast, in post-exposure lactating animals milk fat became an important excretory route removing three-times the quantity of residue cleared in feces. Following parturition, concentrations of PBB in milk fat declined approximately twofold in 6 days. Thereafter, the residue concentration in milk fat was approximately 0.4 that in depot fats. PBB had a predilection for lipid tissues with similar concentrations in various depot fats. Concentrations of the residue were notably low in tissues of the nervous system despite the high content of lipid material. Liver contained residue concentrations that were disproportionately high when compared to the lipid content of the organ. Calves born to PBB-exposed cows had similar distribution of residues in body tissues although concentrations were less than those of the dam."}
{"id": "PMID:210004", "title": "Immunological studies in cattle exposed to polybrominated biphenyls.", "content": "The intactness of the immune system in cattle exposed to polybrominated biphenyls (PBBs) has been investigated by using several immunoassays. Eighty-seven animals have been studied, 35 control animals (not exposed to PBBs) and 52 animals exposed to PBBs (0.02-30 ppm/g fat equivalent). The immunoassays included a complete blood count, identification of peripheral blood T and B lymphocyte subpopulations, serum immunoglobulin levels (IgG, IgM, and IgA), the in vitro response to lymphocytes to phytolectins (PHA, Con A, PWM), the antibody response to Keyhole limpet hemocyanin (KLH), the cell-mediated response to PPD, and determination of autoantibodies and/or immunosuppressive serum factors. For control and PBB-exposed cattle, there was no statistical difference between the number of circulating erythrocytes or leukocytes, the hematocrit, or hemoglobin content; the percentage or number of T and B lymphocytes; the isotope incorporation index (DNA synthesis) of lymphocytes in response to mitogens; the concentrations of serum immunoglobulins IgG, IgM, or IgA; the mean peak titer to KLH; or in vivo or in vitro immune response to PPD.Additional evaluation of cattle with tissue levels of PBB greater than 3 ppm/g tissue for hematological and immunological parameters revealed no statistical difference from control animals. Other experiments were performed to evaluate serum from cattle exposed to PBBs for autoantibodies to smooth muscle, mitochondrial or nuclear antigens. No evidence for autoantibodies was observed. Further studies were done to examine the cytotoxic and/or immunosuppressive activity of sera from PBB-exposed animals. In these studies, the blastogenic response of lymphocytes from control cattle and humans were evaluated in the presence and absence of serum from animals exposed to PBBs (> 3 ppm/g tissue). No evidence for either a cytotoxic or an immunosuppressive influence of such sera was demonstrable. Our studies indicate that PBB, at the levels studied, does not alter or interfere with lymphocyte surface antigens, the complex nuclear and cytoplasmic events required for mitosis and cell division, or the biological events required for antibody formation and cell-mediated immune reactions. Further, PBB exposure at the levels studied does not predispose cattle to autoantibody production or leucotoxic serum factors.", "contents": "Immunological studies in cattle exposed to polybrominated biphenyls. The intactness of the immune system in cattle exposed to polybrominated biphenyls (PBBs) has been investigated by using several immunoassays. Eighty-seven animals have been studied, 35 control animals (not exposed to PBBs) and 52 animals exposed to PBBs (0.02-30 ppm/g fat equivalent). The immunoassays included a complete blood count, identification of peripheral blood T and B lymphocyte subpopulations, serum immunoglobulin levels (IgG, IgM, and IgA), the in vitro response to lymphocytes to phytolectins (PHA, Con A, PWM), the antibody response to Keyhole limpet hemocyanin (KLH), the cell-mediated response to PPD, and determination of autoantibodies and/or immunosuppressive serum factors. For control and PBB-exposed cattle, there was no statistical difference between the number of circulating erythrocytes or leukocytes, the hematocrit, or hemoglobin content; the percentage or number of T and B lymphocytes; the isotope incorporation index (DNA synthesis) of lymphocytes in response to mitogens; the concentrations of serum immunoglobulins IgG, IgM, or IgA; the mean peak titer to KLH; or in vivo or in vitro immune response to PPD.Additional evaluation of cattle with tissue levels of PBB greater than 3 ppm/g tissue for hematological and immunological parameters revealed no statistical difference from control animals. Other experiments were performed to evaluate serum from cattle exposed to PBBs for autoantibodies to smooth muscle, mitochondrial or nuclear antigens. No evidence for autoantibodies was observed. Further studies were done to examine the cytotoxic and/or immunosuppressive activity of sera from PBB-exposed animals. In these studies, the blastogenic response of lymphocytes from control cattle and humans were evaluated in the presence and absence of serum from animals exposed to PBBs (> 3 ppm/g tissue). No evidence for either a cytotoxic or an immunosuppressive influence of such sera was demonstrable. Our studies indicate that PBB, at the levels studied, does not alter or interfere with lymphocyte surface antigens, the complex nuclear and cytoplasmic events required for mitosis and cell division, or the biological events required for antibody formation and cell-mediated immune reactions. Further, PBB exposure at the levels studied does not predispose cattle to autoantibody production or leucotoxic serum factors."}
{"id": "PMID:210005", "title": "Effects of PBBs on cattle. I. Clinical evaluations and clinical chemistry.", "content": "Toxicosis was induced in pregnant heifers by feeding 25,000 mg/head/day of FireMaster BP-6, a commercial blend of polybrominated biphenyls (PBB). The PBB feeding decreased dry matter intake approximately 50% by 4 days exposure. Emaciated animals became anorexic a few days prior to death at 33 to 66 days. Weight losses of heifers average 80 kg. Other clinical signs observed were dehydration, diarrhea, excessive salivation and lacrimation, fetal death, abortion, and general depression as evidenced by depressed heart and respiratory rates. Clinical signs were apparent after 10 days exposure and progressively intensified along with loss of condition until death. Clinicopathologic changes included significantly increased serum glutamic-oxaloacetic transaminase and decreased serum calcium by 30 days exposure. Lactate dehydrogenase, urea nitrogen, and bilirubin were elevated, and serum albumin decreased by 36 to 40 days. Principal urine changes were decreased specific gravity and moderate proteinuria. Pregnant heifers fed 0.25 or 250 mg/head/day for 60 days and nonpregnant heifers fed 250 mg/head/day for 180 days displayed neither clinical signs nor clinicopathologic changes indicating adverse effects from PBB exposure. Post-exposure, all heifers exposed to PBB for 60 days calved normally with zero calf mortality and were successfully rebred. Milk production was not different from control animals. Birth weights of calves from dams exposed to 250 mg PBB/head/day were significantly greater than calves of dams exposed to 0 mg or 0.25 mg/head/day. PBB exposure of dams produced no detrimental effects on calves as indicated by clinical signs, clinicopathologic changes, or performance.", "contents": "Effects of PBBs on cattle. I. Clinical evaluations and clinical chemistry. Toxicosis was induced in pregnant heifers by feeding 25,000 mg/head/day of FireMaster BP-6, a commercial blend of polybrominated biphenyls (PBB). The PBB feeding decreased dry matter intake approximately 50% by 4 days exposure. Emaciated animals became anorexic a few days prior to death at 33 to 66 days. Weight losses of heifers average 80 kg. Other clinical signs observed were dehydration, diarrhea, excessive salivation and lacrimation, fetal death, abortion, and general depression as evidenced by depressed heart and respiratory rates. Clinical signs were apparent after 10 days exposure and progressively intensified along with loss of condition until death. Clinicopathologic changes included significantly increased serum glutamic-oxaloacetic transaminase and decreased serum calcium by 30 days exposure. Lactate dehydrogenase, urea nitrogen, and bilirubin were elevated, and serum albumin decreased by 36 to 40 days. Principal urine changes were decreased specific gravity and moderate proteinuria. Pregnant heifers fed 0.25 or 250 mg/head/day for 60 days and nonpregnant heifers fed 250 mg/head/day for 180 days displayed neither clinical signs nor clinicopathologic changes indicating adverse effects from PBB exposure. Post-exposure, all heifers exposed to PBB for 60 days calved normally with zero calf mortality and were successfully rebred. Milk production was not different from control animals. Birth weights of calves from dams exposed to 250 mg PBB/head/day were significantly greater than calves of dams exposed to 0 mg or 0.25 mg/head/day. PBB exposure of dams produced no detrimental effects on calves as indicated by clinical signs, clinicopathologic changes, or performance."}
{"id": "PMID:210006", "title": "Absence of plant uptake and translocation of polybrominated biphenyls (PBBs).", "content": "Studies of polybrominated biphenyl (PBB) uptake by plants have been conducted in hydroponic solutions and in greenhouse experiments with soil. Autoradiograms of corn and soybean seedlings grown in hydroponic solutions showed no translocation of 14C-PBB from 14C-PBB-treated solutions to plant tops or within the leaf from 14C-PBB-treated spots on the upper leaf surface. A significant portion of the 14C-PBB associated with the roots was removed when the roots were dipped in acetone. Three root crops (radishes, carrots, and onions) were grown in two soils, each treated with a mixture of FireMaster BP-6 (PBB) and 14C-PBB to achieve final concentrations of 100 ppm and 100 ppb. All roots showed more PBB when grown in the soil with the lower clay and organic matter content than they did when grown in the soil with more clay and organic matter. In the latter soil (clay loam) no PBB was detected in any roots from the 100 ppb treatment. More PBB was associated with roots of carrot than of radish or onion. Corn leaf whorls containing dust from a PBB contamination soil and washed radishes from a heavily contaminated garden showed no PBB.", "contents": "Absence of plant uptake and translocation of polybrominated biphenyls (PBBs). Studies of polybrominated biphenyl (PBB) uptake by plants have been conducted in hydroponic solutions and in greenhouse experiments with soil. Autoradiograms of corn and soybean seedlings grown in hydroponic solutions showed no translocation of 14C-PBB from 14C-PBB-treated solutions to plant tops or within the leaf from 14C-PBB-treated spots on the upper leaf surface. A significant portion of the 14C-PBB associated with the roots was removed when the roots were dipped in acetone. Three root crops (radishes, carrots, and onions) were grown in two soils, each treated with a mixture of FireMaster BP-6 (PBB) and 14C-PBB to achieve final concentrations of 100 ppm and 100 ppb. All roots showed more PBB when grown in the soil with the lower clay and organic matter content than they did when grown in the soil with more clay and organic matter. In the latter soil (clay loam) no PBB was detected in any roots from the 100 ppb treatment. More PBB was associated with roots of carrot than of radish or onion. Corn leaf whorls containing dust from a PBB contamination soil and washed radishes from a heavily contaminated garden showed no PBB."}
{"id": "PMID:210007", "title": "Toxicity and residue studies in dairy animals with firemaster FF-1 (polybrominated biphenyls).", "content": "Two studies (one in Holstein calves and one in Holstein cows) were conducted to determine potential toxicity and residue levels following oral ingestion of polybrominated biphenyls (PBB). The material was FireMaster FF-1. Administration was by gelatin capsules. Doses in calves were 0.1, 1.0, 10, or 100 mg/kg body weight, while doses in cows were equivalent to 0.01, 0.1, 1.0, or 10 ppm in the diet. The calves were sacrificed after 2, 4, 6, or 12 weeks. The cows were fed 158 or 228 days, and were then in a recovery period for 182 or 112 days. In the calf study, signs of toxicity were observed only in animals fed 100 mg/kg-day. Administration of 10 mg/kg-day or less for up to 12 weeks caused no overt signs of toxicity. Histologic studies were conducted upon selected organs and tissues taken at time of sacrifice. The only treatment-induced lesions among animals fed 0.1 mg/kg-day were minimal lesions in the kidney and skin in the one calf fed at this level for 12 weeks. Treatment-induced lesions were present in the kidneys, skin, and/or liver from some animals fed levels of 1.0 mg/kg-day and above. The relative severity of these lesions was related to the level and length of exposure. Treatment-associated changes were observed in the testes of all males in this study. The hypospermatogenesis observed was consistent with the age of the animals due to prepuberal development of the testes. No clinical signs of toxicity or histologic changes attributed to PBB were observed in the cows. Two cows were pregnant at the initiation of the study and give birth to normal, healthy calves during the study. These calves grew normally and appeared healthy when sacrificed at about 6 months of age. Residue levels were quantitated as the hexabromobiphenyl isomer (BP-6) which is the major isomer present in the PBB mixture. Tissue residue levels in calves increased with dose and duration of administration of PBB with highest levels being found in the fat. At 100 mg/kg the levels in fat were about 6000 to 6300 ppm after 6 to 12 weeks. Residue levels of BP-6 in milk and fat of the cows also increased with dose and duration of administration. Maximum levels in milk were about 1/3 the levels in the diet. In general, the levels plateaued after about 4 to 6 weeks and did not go appreciably higher even though administration of the FireMaster FF-1 was continued. Maximum levels in fat were on the order of approximately 4.5 times the levels in the diet, except at the lowest dose level. Residues decreased in milk after administration of PBB was discontinued, but detectable levels were still present 6 months later. Residues were found in the calves born of treated cows indicating passage of the PBBs through the placental barrier and/or ingestion through the milk.", "contents": "Toxicity and residue studies in dairy animals with firemaster FF-1 (polybrominated biphenyls). Two studies (one in Holstein calves and one in Holstein cows) were conducted to determine potential toxicity and residue levels following oral ingestion of polybrominated biphenyls (PBB). The material was FireMaster FF-1. Administration was by gelatin capsules. Doses in calves were 0.1, 1.0, 10, or 100 mg/kg body weight, while doses in cows were equivalent to 0.01, 0.1, 1.0, or 10 ppm in the diet. The calves were sacrificed after 2, 4, 6, or 12 weeks. The cows were fed 158 or 228 days, and were then in a recovery period for 182 or 112 days. In the calf study, signs of toxicity were observed only in animals fed 100 mg/kg-day. Administration of 10 mg/kg-day or less for up to 12 weeks caused no overt signs of toxicity. Histologic studies were conducted upon selected organs and tissues taken at time of sacrifice. The only treatment-induced lesions among animals fed 0.1 mg/kg-day were minimal lesions in the kidney and skin in the one calf fed at this level for 12 weeks. Treatment-induced lesions were present in the kidneys, skin, and/or liver from some animals fed levels of 1.0 mg/kg-day and above. The relative severity of these lesions was related to the level and length of exposure. Treatment-associated changes were observed in the testes of all males in this study. The hypospermatogenesis observed was consistent with the age of the animals due to prepuberal development of the testes. No clinical signs of toxicity or histologic changes attributed to PBB were observed in the cows. Two cows were pregnant at the initiation of the study and give birth to normal, healthy calves during the study. These calves grew normally and appeared healthy when sacrificed at about 6 months of age. Residue levels were quantitated as the hexabromobiphenyl isomer (BP-6) which is the major isomer present in the PBB mixture. Tissue residue levels in calves increased with dose and duration of administration of PBB with highest levels being found in the fat. At 100 mg/kg the levels in fat were about 6000 to 6300 ppm after 6 to 12 weeks. Residue levels of BP-6 in milk and fat of the cows also increased with dose and duration of administration. Maximum levels in milk were about 1/3 the levels in the diet. In general, the levels plateaued after about 4 to 6 weeks and did not go appreciably higher even though administration of the FireMaster FF-1 was continued. Maximum levels in fat were on the order of approximately 4.5 times the levels in the diet, except at the lowest dose level. Residues decreased in milk after administration of PBB was discontinued, but detectable levels were still present 6 months later. Residues were found in the calves born of treated cows indicating passage of the PBBs through the placental barrier and/or ingestion through the milk."}
{"id": "PMID:210008", "title": "Effects of polybrominated biphenyl on milk production, reproduction, and health problems in Holstein cows.", "content": "PBB found in relatively low levels among animals present on a cross-section of Michigan farms during the time PBB was inadvertantly added to dairy feeds had no effect upon these animals' milk production, body weight, weight gain, breeding and reproduction performance, incidence of commonly experienced health problems, calving rate, and the health of their calves. No significant differences in these vital areas could be seen between Michigan animals exposed to PBB and equivalent Wisconsin animals which had not been exposed to PBB when both groups were subjected to equivalent management practices. No pattern of gross of histopathological lesions was seen upon necropsy between test animals and control animals.", "contents": "Effects of polybrominated biphenyl on milk production, reproduction, and health problems in Holstein cows. PBB found in relatively low levels among animals present on a cross-section of Michigan farms during the time PBB was inadvertantly added to dairy feeds had no effect upon these animals' milk production, body weight, weight gain, breeding and reproduction performance, incidence of commonly experienced health problems, calving rate, and the health of their calves. No significant differences in these vital areas could be seen between Michigan animals exposed to PBB and equivalent Wisconsin animals which had not been exposed to PBB when both groups were subjected to equivalent management practices. No pattern of gross of histopathological lesions was seen upon necropsy between test animals and control animals."}
{"id": "PMID:210015", "title": "Limited tryptic digestion of human serum low-density lipoprotein: isolation and characterisation of the protein-deficient particle and of its apoprotein.", "content": "Limited tryptic digestion of human serum low-density (LD) lipoprotein (rho 1.024-1.045 g/ml) under defined conditions permitted isolation by gel filtration chromatography of a stable, protein-deficient lipoprotein; the liberated protein was separated as a mixture of peptides of low molecular weight (less than 5000). Comparison of the chemical, physical and immunological characteristics of the trypsin-treated LD-lipoprotein with those of the native preparation revealed several differences, including (a) a diminished protein content (loss of some 20-25% of the total protein of LD-lipoprotein) and increased proportions of the various lipid components, except for triglyceride (probably resulting from a loss of bound free fatty acids with the liberated peptides); (b) a greater heterogeneity in particle size and slightly larger mean diameter; (c) a lower hydrated density and greater peak sf rate than the native LD-lipoprotein (d) an increased net negative charge; and (e) a partial immunological identity between LD-lipoprotein and the corresponding trypsin-treated fraction. While the amino acid compositions of the protein moieties of LD-lipoprotein and of trypsin-treated LD-lipoprotein were essentially identical, trypsin-treated apo-LD-lipoprotein was distinct in its complete solubility in urea-containing buffers at high concentrations, and also in its partial solubility in buffers lacking denaturing agents. Comparison of the apoproteins of the native and trypsin-treated LD-lipoproteins by electrophoretic techniques based on molecular weight revealed a transformation of the high-molecular weight material (greater than 250 000) characteristic of apo-LD lipoprotein into several polypeptide species (10 major forms) ranging in size from 161 500 to about 10 000. The largest of these (band b1: 161 500) could be completely dissociated into smaller components (b2: 93 500 and b3: 77 000) upon extensive heat treatment at 90 degrees C. Electrophoresis of the soluble fraction of apo-LD-lipoprotein and of that from its trypsin-treated counterpart in polyacrylamide gels containing urea at basic pH showed the disappearance of the small amounts (less than 5%) of C apoproteins of apo-LD-lipoprotein upon tryptic treatment. These results, which were highly reproducible in LD-lipoprotein preparations from different individuals, suggest that trypsin-treated LD-lipoprotein may provide a model for investigation of the organisation and structural role of the prinicipal apoprotein (apolipoprotein-B) in the LD-lipoprotein molecule.", "contents": "Limited tryptic digestion of human serum low-density lipoprotein: isolation and characterisation of the protein-deficient particle and of its apoprotein. Limited tryptic digestion of human serum low-density (LD) lipoprotein (rho 1.024-1.045 g/ml) under defined conditions permitted isolation by gel filtration chromatography of a stable, protein-deficient lipoprotein; the liberated protein was separated as a mixture of peptides of low molecular weight (less than 5000). Comparison of the chemical, physical and immunological characteristics of the trypsin-treated LD-lipoprotein with those of the native preparation revealed several differences, including (a) a diminished protein content (loss of some 20-25% of the total protein of LD-lipoprotein) and increased proportions of the various lipid components, except for triglyceride (probably resulting from a loss of bound free fatty acids with the liberated peptides); (b) a greater heterogeneity in particle size and slightly larger mean diameter; (c) a lower hydrated density and greater peak sf rate than the native LD-lipoprotein (d) an increased net negative charge; and (e) a partial immunological identity between LD-lipoprotein and the corresponding trypsin-treated fraction. While the amino acid compositions of the protein moieties of LD-lipoprotein and of trypsin-treated LD-lipoprotein were essentially identical, trypsin-treated apo-LD-lipoprotein was distinct in its complete solubility in urea-containing buffers at high concentrations, and also in its partial solubility in buffers lacking denaturing agents. Comparison of the apoproteins of the native and trypsin-treated LD-lipoproteins by electrophoretic techniques based on molecular weight revealed a transformation of the high-molecular weight material (greater than 250 000) characteristic of apo-LD lipoprotein into several polypeptide species (10 major forms) ranging in size from 161 500 to about 10 000. The largest of these (band b1: 161 500) could be completely dissociated into smaller components (b2: 93 500 and b3: 77 000) upon extensive heat treatment at 90 degrees C. Electrophoresis of the soluble fraction of apo-LD-lipoprotein and of that from its trypsin-treated counterpart in polyacrylamide gels containing urea at basic pH showed the disappearance of the small amounts (less than 5%) of C apoproteins of apo-LD-lipoprotein upon tryptic treatment. These results, which were highly reproducible in LD-lipoprotein preparations from different individuals, suggest that trypsin-treated LD-lipoprotein may provide a model for investigation of the organisation and structural role of the prinicipal apoprotein (apolipoprotein-B) in the LD-lipoprotein molecule."}
{"id": "PMID:210017", "title": "Structural studies of iron and cobalt tetrasulfonated phthalocyanine-globin complexes.", "content": "The structure of the complexes of iron and cobalt tetrasulfonated phthalocyanines with globin has been investigated by circular dichroism (CD), electron paramagnetic resonance (EPR) and polyacrylamide gel electrophoresis. Electrophoretic investigations and the molecular weight estimation indicates that the model complexes in the solutions are dimers. It is evident from the results of CD measurements that the incorporation of the iron or cobalt tetrasulfonated phthalocyanine into apohemoglobin significantly increases the helical structure of the protein and causes an appearance of the induced Soret and visible Cotton effects. Unlike methemoglobin, several discrete transition energies in the CD Soret band of Fe(III)L-globin are observed which suggest an inequivalence of the subunits within this complex. This suggestion is supported by EPR studies, which show that the iron atoms in Fe(III)L-globin are in two low electronic states. Electronic structures of the cobalt ions in Co(II)L-globin and oxyCo(II)L-globin are similar to those of coboglobin and oxycoboglobin, respectively, as is proved by EPR results. On this basis we conclude that the oxygen adduct of Co(II)L-globin can be described as a superoxide ion corrdinated to a formally cobaltic phthalocyanine compound.", "contents": "Structural studies of iron and cobalt tetrasulfonated phthalocyanine-globin complexes. The structure of the complexes of iron and cobalt tetrasulfonated phthalocyanines with globin has been investigated by circular dichroism (CD), electron paramagnetic resonance (EPR) and polyacrylamide gel electrophoresis. Electrophoretic investigations and the molecular weight estimation indicates that the model complexes in the solutions are dimers. It is evident from the results of CD measurements that the incorporation of the iron or cobalt tetrasulfonated phthalocyanine into apohemoglobin significantly increases the helical structure of the protein and causes an appearance of the induced Soret and visible Cotton effects. Unlike methemoglobin, several discrete transition energies in the CD Soret band of Fe(III)L-globin are observed which suggest an inequivalence of the subunits within this complex. This suggestion is supported by EPR studies, which show that the iron atoms in Fe(III)L-globin are in two low electronic states. Electronic structures of the cobalt ions in Co(II)L-globin and oxyCo(II)L-globin are similar to those of coboglobin and oxycoboglobin, respectively, as is proved by EPR results. On this basis we conclude that the oxygen adduct of Co(II)L-globin can be described as a superoxide ion corrdinated to a formally cobaltic phthalocyanine compound."}
{"id": "PMID:210018", "title": "Refolding and reactivation of liver alcohol dehydrogenase after dissociation and denaturation in 6M guanidine hydrochloride.", "content": "Horse-liver alcohol dehydrogenase has been dissociated and denatured by 6 M guanidinium hydrochloride. Removal of the denaturant under optimum conditions of the solvent leads to partial reactivation. The concentrations of the enzyme, as well as the coenzyme (NAD+), and Zn2+, affect the reactivation significantly, since high concentrations promote the formation of inactive aggregation products. Analyzing the kinetics of reactivation and reassociation, conditions far from equilibrium of dissociation-association provide maximum yields (approximately 70%). The sigmoidal kinetic traces suggest a superposition of first-order transconformation and second-order association reactions; the latter are corroborated by the concentration dependence of the reactivation reaction. The coenzyme, NAD+, has no influence on the kinetics of reactivation. Addition of Zn2+ leads to a significant decrease of the rate and yield of reactivation. The process of renaturation, as reflected by the regain of native fluorescence shows complex kinetics: rapid relaxations are followed by slower first-order and second-order processes which parallel reactivation.", "contents": "Refolding and reactivation of liver alcohol dehydrogenase after dissociation and denaturation in 6M guanidine hydrochloride. Horse-liver alcohol dehydrogenase has been dissociated and denatured by 6 M guanidinium hydrochloride. Removal of the denaturant under optimum conditions of the solvent leads to partial reactivation. The concentrations of the enzyme, as well as the coenzyme (NAD+), and Zn2+, affect the reactivation significantly, since high concentrations promote the formation of inactive aggregation products. Analyzing the kinetics of reactivation and reassociation, conditions far from equilibrium of dissociation-association provide maximum yields (approximately 70%). The sigmoidal kinetic traces suggest a superposition of first-order transconformation and second-order association reactions; the latter are corroborated by the concentration dependence of the reactivation reaction. The coenzyme, NAD+, has no influence on the kinetics of reactivation. Addition of Zn2+ leads to a significant decrease of the rate and yield of reactivation. The process of renaturation, as reflected by the regain of native fluorescence shows complex kinetics: rapid relaxations are followed by slower first-order and second-order processes which parallel reactivation."}
{"id": "PMID:210019", "title": "Occurrence of secondary cystathioninuria in children with inherited metabolic disorders, liver diseases, neoplasms, cystic fibrosis and celiac disease.", "content": "Secondary cystathioninuria was found in two of 46 children suffering from tumors, leukemia, liver disease, inherited metabolic disorders, cystic fibrosis and celiac disease. Of these two patients, one had congenital biliary atresia and the other cytomegalovirus infection. Seven further children had only moderately elevated excretion of cystathionine. It is suggested that secondary cystathioninuria is uncommon in the disease investigated.", "contents": "Occurrence of secondary cystathioninuria in children with inherited metabolic disorders, liver diseases, neoplasms, cystic fibrosis and celiac disease. Secondary cystathioninuria was found in two of 46 children suffering from tumors, leukemia, liver disease, inherited metabolic disorders, cystic fibrosis and celiac disease. Of these two patients, one had congenital biliary atresia and the other cytomegalovirus infection. Seven further children had only moderately elevated excretion of cystathionine. It is suggested that secondary cystathioninuria is uncommon in the disease investigated."}
{"id": "PMID:210020", "title": "Superior orbital fissure syndrome. Review of 130 cases.", "content": "Superior orbital fissure syndrome is a symptomatologic complex, consisting of retroorbital pain, paralysis of extraocular muscles, impairment of first trigeminal branches and frequent involvement of the optic nerve. From a review of 130 published cases including two personal observations, it appears that the clinical subdivisions and the several eponymic differentiations of this syndrome are unjustified on the basis of etiologic, therapeutic and prognostic elements. Only the presence--or absence--of optic signs may allow to hold the clinically useful distinction between the often 'benign' superior orbital fissure syndrome without optic nerve involvement, and the orbital apex syndrome where orbital exploration may be recommended. This review concludes that repeated neurosurgical and neuroradiologic investigations--with the exceptions of carotid angiography and orbital phlebography--can be avoided in such cases.", "contents": "Superior orbital fissure syndrome. Review of 130 cases. Superior orbital fissure syndrome is a symptomatologic complex, consisting of retroorbital pain, paralysis of extraocular muscles, impairment of first trigeminal branches and frequent involvement of the optic nerve. From a review of 130 published cases including two personal observations, it appears that the clinical subdivisions and the several eponymic differentiations of this syndrome are unjustified on the basis of etiologic, therapeutic and prognostic elements. Only the presence--or absence--of optic signs may allow to hold the clinically useful distinction between the often 'benign' superior orbital fissure syndrome without optic nerve involvement, and the orbital apex syndrome where orbital exploration may be recommended. This review concludes that repeated neurosurgical and neuroradiologic investigations--with the exceptions of carotid angiography and orbital phlebography--can be avoided in such cases."}
{"id": "PMID:210021", "title": "Nerve conduction velocity of small components in human sensory nerves. Studies in normal and diseased nerves.", "content": "Slow conducted components of sensory nerve action potentials were investigated in median and in sural nerves of controls and in patients with peripheral nerve diseases. In the normal group the slow components showed no relation to age which is in contrast to the maximum velocity. In both the median nerve and sural nerve of about 20% of the patients with neuropathy exclusively a decrease of the conduction velocity of slow components was found, the other investigated parameters were normal. Possible causes are an alternation of the myelin sheath or changes in the properties of the nodal gap membrane.", "contents": "Nerve conduction velocity of small components in human sensory nerves. Studies in normal and diseased nerves. Slow conducted components of sensory nerve action potentials were investigated in median and in sural nerves of controls and in patients with peripheral nerve diseases. In the normal group the slow components showed no relation to age which is in contrast to the maximum velocity. In both the median nerve and sural nerve of about 20% of the patients with neuropathy exclusively a decrease of the conduction velocity of slow components was found, the other investigated parameters were normal. Possible causes are an alternation of the myelin sheath or changes in the properties of the nodal gap membrane."}
{"id": "PMID:210022", "title": "Homovanillic acid and 5-hydroxyindoleacetic acid in lumbar cerebrospinal fluid after total and REM sleep deprivation in humans.", "content": "Lumbar CSF HVA and 5-HIAA levels were assayed in 3 groups each of 10 subjects, which were respectively deprived of sleep for 30 h, deprived of REM sleep and disturbed with several awakenings during SW sleep for two consecutive nights. HVA levels after total sleep (39 +/- 20 ng/ml) or REM (35 +/- 11 ng/ml) deprivation as well as after SW sleep awakenings (32 +/- 26 ng/ml) were not different from controls (42 +/- 14 ng/ml). 5-HIAA levels after REM deprivation (32 +/- 15 ng/ml) appeared increased when compared with controls (21 +/- 7 ng/ml), total sleep-deprived subjects (21 +/- 10 ng/ml) or subjects with SW sleep awakenings (27 +/- 13 ng/ml). Possible increase in 5-HT turnover after REM deprivation and possible 5-HT role in REM sleep regulation in humans are discussed.", "contents": "Homovanillic acid and 5-hydroxyindoleacetic acid in lumbar cerebrospinal fluid after total and REM sleep deprivation in humans. Lumbar CSF HVA and 5-HIAA levels were assayed in 3 groups each of 10 subjects, which were respectively deprived of sleep for 30 h, deprived of REM sleep and disturbed with several awakenings during SW sleep for two consecutive nights. HVA levels after total sleep (39 +/- 20 ng/ml) or REM (35 +/- 11 ng/ml) deprivation as well as after SW sleep awakenings (32 +/- 26 ng/ml) were not different from controls (42 +/- 14 ng/ml). 5-HIAA levels after REM deprivation (32 +/- 15 ng/ml) appeared increased when compared with controls (21 +/- 7 ng/ml), total sleep-deprived subjects (21 +/- 10 ng/ml) or subjects with SW sleep awakenings (27 +/- 13 ng/ml). Possible increase in 5-HT turnover after REM deprivation and possible 5-HT role in REM sleep regulation in humans are discussed."}
{"id": "PMID:210023", "title": "Prazosin and presynaptic alpha-receptors in the cardioaccelerator nerve of the dog.", "content": "In vagotomized, spinal-sectioned dogs, prazosin and phentolamine enhanced positive chronotropic responses to cardiac accelerator nerve stimulation. In additional dogs the inhibition by clonidine of heart rate response to continuous accelerator nerve stimulation (presynaptic effect), and the vasopressor effect of clonidine (post-synaptic effect), were antagonized by prazosin, phentolamine and yohimbine; cumulative doses for 50% antagonism of the cardiac chronotropic effect were 103, 50 and 13 microgram/kg i.v., respectively, and those for 50% antagonism of the vasopressor effect were 39, 38 and 3 microgram/kg i.v., respectively. On isolated rabbit pulmonary artery, prazosin antagonized electrically evoked contractions but had no effect on 3H output, whereas yohimbine enhanced both. The results indicate that prazosin, like phentolamine and yohimbine, blocks presynaptic alpha-adrenergic receptors on the cardiac accelerator nerve of the dog but, unlike yohimbine, prazosin does not block these receptors on noradrenergic nerves of rabbit pulmonary artery. It is concluded that the relative activity of a compound at pre- and postsynaptic alpha-receptors is not the same for all organs. The results are discussed relative to the fact that prazosin causes hypotension without significant reflex tachycardia in dog and man.", "contents": "Prazosin and presynaptic alpha-receptors in the cardioaccelerator nerve of the dog. In vagotomized, spinal-sectioned dogs, prazosin and phentolamine enhanced positive chronotropic responses to cardiac accelerator nerve stimulation. In additional dogs the inhibition by clonidine of heart rate response to continuous accelerator nerve stimulation (presynaptic effect), and the vasopressor effect of clonidine (post-synaptic effect), were antagonized by prazosin, phentolamine and yohimbine; cumulative doses for 50% antagonism of the cardiac chronotropic effect were 103, 50 and 13 microgram/kg i.v., respectively, and those for 50% antagonism of the vasopressor effect were 39, 38 and 3 microgram/kg i.v., respectively. On isolated rabbit pulmonary artery, prazosin antagonized electrically evoked contractions but had no effect on 3H output, whereas yohimbine enhanced both. The results indicate that prazosin, like phentolamine and yohimbine, blocks presynaptic alpha-adrenergic receptors on the cardiac accelerator nerve of the dog but, unlike yohimbine, prazosin does not block these receptors on noradrenergic nerves of rabbit pulmonary artery. It is concluded that the relative activity of a compound at pre- and postsynaptic alpha-receptors is not the same for all organs. The results are discussed relative to the fact that prazosin causes hypotension without significant reflex tachycardia in dog and man."}
{"id": "PMID:210024", "title": "Increased noradrenaline release in rat portal vein during sympathetic nerve stimulation due to activation of presynaptic beta-adrenoceptors by noradrenaline and adrenaline.", "content": "With the aim of investigating whether exogenous noradrenaline (NA) and adrenaline (A) can modulate transmitter release via the stimulation of presynaptic beta-adrenoceptors, 3H-release from isolated portal veins was studied after pretreatment with 3H-1-NA, phenoxybenzamine, desipramine and normetanephrine. NA (10 muM) and A (0.05 muM) increased the fractional 3H-release elicited by sympathetic nerve stimulation by 30%. This effect could be blocked by d, 1-propranolol which per se reduced the release by 10%. It is concluded that NA can facilitate its own release via a presynaptic beta-adrenoceptor-mediated positive feed-back mechanism and that adrenaline can stimulate this beta-adrenoceptor-mediated mechanism.", "contents": "Increased noradrenaline release in rat portal vein during sympathetic nerve stimulation due to activation of presynaptic beta-adrenoceptors by noradrenaline and adrenaline. With the aim of investigating whether exogenous noradrenaline (NA) and adrenaline (A) can modulate transmitter release via the stimulation of presynaptic beta-adrenoceptors, 3H-release from isolated portal veins was studied after pretreatment with 3H-1-NA, phenoxybenzamine, desipramine and normetanephrine. NA (10 muM) and A (0.05 muM) increased the fractional 3H-release elicited by sympathetic nerve stimulation by 30%. This effect could be blocked by d, 1-propranolol which per se reduced the release by 10%. It is concluded that NA can facilitate its own release via a presynaptic beta-adrenoceptor-mediated positive feed-back mechanism and that adrenaline can stimulate this beta-adrenoceptor-mediated mechanism."}
{"id": "PMID:210025", "title": "Specific antagonism of excitant amino acids in the isolated spinal cord of the neonatal rat.", "content": "The specificity of the neurodepressant actions of D-alpha-aminoadipate, alpha,epsilon-diaminopimelic acid, HA-966 (HAP) and Mg2+ has been investigated. On the isolated spinal cord of the neonatal rat, ventral root depolarizations produced by kainate, substance P, carbachol and noradrenaline were relatively unaffected by the same concentrations (0.25--1 mM) of the agents as those which reduced synaptic activity and ventral root depolarizations produced by N-methyl-D-aspartate (especially), L-aspartate and L-glutamate. The same or higher concentrations of the agents did not affect excitatory transmission in the isolated rat superior cervical ganglion. It is proposed that the agents specifically block synaptic transmission mediated by an excitatory amino acid.", "contents": "Specific antagonism of excitant amino acids in the isolated spinal cord of the neonatal rat. The specificity of the neurodepressant actions of D-alpha-aminoadipate, alpha,epsilon-diaminopimelic acid, HA-966 (HAP) and Mg2+ has been investigated. On the isolated spinal cord of the neonatal rat, ventral root depolarizations produced by kainate, substance P, carbachol and noradrenaline were relatively unaffected by the same concentrations (0.25--1 mM) of the agents as those which reduced synaptic activity and ventral root depolarizations produced by N-methyl-D-aspartate (especially), L-aspartate and L-glutamate. The same or higher concentrations of the agents did not affect excitatory transmission in the isolated rat superior cervical ganglion. It is proposed that the agents specifically block synaptic transmission mediated by an excitatory amino acid."}
{"id": "PMID:210029", "title": "Convergence of cerebral inputs onto dentate neurons in monkey.", "content": "The patterns of convergence of inputs from different areas of the cerebral cortex and the peripheral nerves onto single dentate neurons was studied in cebus monkeys. Dentate neurons receive their strongest and most numerous inputs from the premotor and supplementary motor regions of area 6. The sensorimotor and frontal cortices have weaker projections to the dentate nucleus, while peripheral nerves and many other association cortical areas were found to be effective in influencing cells of the lateral cerebellum. Dentate cells that respond to stimulation of hindlimb regions of the sensorimotor cortex tend to receive their principal input from the supplementary motor area and medial premotor regions, while neurons responding to forelimb sensorimotor cortex tend to receive lateral premotor inputs. In addition there is a topographical organization within the ventral pole of dentate with the hindlimb represented in the anterior regions and the forelimb in the posterior regions. These results are compared with those of similar studies of interpositus and dentate neurons in cat and monkey. The differences between the afferent inputs to dentate and interpositus are consistent with the suggestion that the lateral cerebellum is involved in programming movement parameters before movement initiation while the intermediate zone is involved in up-dating the evolving movement.", "contents": "Convergence of cerebral inputs onto dentate neurons in monkey. The patterns of convergence of inputs from different areas of the cerebral cortex and the peripheral nerves onto single dentate neurons was studied in cebus monkeys. Dentate neurons receive their strongest and most numerous inputs from the premotor and supplementary motor regions of area 6. The sensorimotor and frontal cortices have weaker projections to the dentate nucleus, while peripheral nerves and many other association cortical areas were found to be effective in influencing cells of the lateral cerebellum. Dentate cells that respond to stimulation of hindlimb regions of the sensorimotor cortex tend to receive their principal input from the supplementary motor area and medial premotor regions, while neurons responding to forelimb sensorimotor cortex tend to receive lateral premotor inputs. In addition there is a topographical organization within the ventral pole of dentate with the hindlimb represented in the anterior regions and the forelimb in the posterior regions. These results are compared with those of similar studies of interpositus and dentate neurons in cat and monkey. The differences between the afferent inputs to dentate and interpositus are consistent with the suggestion that the lateral cerebellum is involved in programming movement parameters before movement initiation while the intermediate zone is involved in up-dating the evolving movement."}
{"id": "PMID:210030", "title": "Properties of a new vestibulospinal projection, the caudal vestibulospinal tract.", "content": "Neurons in the caudal portions of the medial and descending vestibular nuclei and in vestibular cell group f that project to the cervical or lumbar spinal cord were located by antidromic spinal stimulation. These caudal vestibulospinal tract (CVST) neurons have a median conduction velocity of 12 m/sec, which is well below the conduction velocities of typical lateral or medial vestibulospinal tract (LVST, MVST) axons. The descending fiber trajectories of CVST neurons, determined by comparing thresholds for activation of each neuron from six points in the spinal white matter, were remarkably diverse. Unlike LVST and MVST axons, which are located in the ipsilateral ventral funiculi, CVST axons can be found in both the ventral and dorsolateral funiculi on both sides of the spinal cord. The CVST system is thus both anatomically and physiologically different from the LVST and MVST.", "contents": "Properties of a new vestibulospinal projection, the caudal vestibulospinal tract. Neurons in the caudal portions of the medial and descending vestibular nuclei and in vestibular cell group f that project to the cervical or lumbar spinal cord were located by antidromic spinal stimulation. These caudal vestibulospinal tract (CVST) neurons have a median conduction velocity of 12 m/sec, which is well below the conduction velocities of typical lateral or medial vestibulospinal tract (LVST, MVST) axons. The descending fiber trajectories of CVST neurons, determined by comparing thresholds for activation of each neuron from six points in the spinal white matter, were remarkably diverse. Unlike LVST and MVST axons, which are located in the ipsilateral ventral funiculi, CVST axons can be found in both the ventral and dorsolateral funiculi on both sides of the spinal cord. The CVST system is thus both anatomically and physiologically different from the LVST and MVST."}
{"id": "PMID:210031", "title": "Functional organization of the corticofugal system from visual cortex to lateral geniculate nucleus in the cat (with an appendix on geniculo-cortical mono-synaptic connections).", "content": "1. In the cat visual cortex (VC), electrophoretic glutamate application at a depth corresponding to layer VI may have excitatory or inhibitory effects on relay cells of the lateral geniculate nucleus (LGN). Corticofugal excitation was seen, if the receptive field centers (RFCs) of the VC neurons recorded at the application site were within 2.3 degrees of the RFCs of the LGN neurons under test. Inhibitory effects were seen if the RFCs of both cells were further apart up to 3.1 degrees. Glutamate application at more superficial cortical sites had no effect on LGN-neuron activity. 2. Cross-correlation analysis between spontaneous activities of simultaneously recorded VC and LGN neurons revealed excitatory cortico-geniculate connections in 18 pairs with RFCs separated by less than 1.7 degrees. In 15 pairs the peak latency of the excitation was 2--5 msec (3.4 msec in the average), 3 pairs showed long cortico-geniculate latencies (13--18 msec). The existence of a fast and slow cortico-geniculate system is suggested. 3. Inhibitory cortico-geniculate interaction was demonstrated with cross-correlation analysis in 8 pairs of which 4 had RFCs separated by more than 1.7 degrees. The onset latency of the inhibition was 2--7 msec except for 2 pairs with about 20 msec latency. 4. Most of the LGN neurons which were affected by cortical glutamate application or which showed an excitatory or inhibitory connection with a VC neurons were sustained cells, while the majority of VC neurons which were recorded in the effective glutamate application sites or which showed a significant interaction with LGN neurons in the cross-correlogram were binocularly driven and complex, with mostly large RFCs (mean diameter 3.5 degrees). They responded briskly to moving small spots as well as to moving slits. 5. It is concluded that the corticofugal excitatory effect is transmitted through monosynaptic links from VC neurons located in layer VI (complex cell) to LGN relay neurons (mostly sustained-cell) and this system is organized in a precise topographical manner. 6. In an Appendix neuron pairs which showed a positive correlation in the geniculo-cortical direction were described. The findings may support the view that complex as well as simple cells are drive monosynaptically from geniculo-cortical afferents of the sustained or transient type.", "contents": "Functional organization of the corticofugal system from visual cortex to lateral geniculate nucleus in the cat (with an appendix on geniculo-cortical mono-synaptic connections). 1. In the cat visual cortex (VC), electrophoretic glutamate application at a depth corresponding to layer VI may have excitatory or inhibitory effects on relay cells of the lateral geniculate nucleus (LGN). Corticofugal excitation was seen, if the receptive field centers (RFCs) of the VC neurons recorded at the application site were within 2.3 degrees of the RFCs of the LGN neurons under test. Inhibitory effects were seen if the RFCs of both cells were further apart up to 3.1 degrees. Glutamate application at more superficial cortical sites had no effect on LGN-neuron activity. 2. Cross-correlation analysis between spontaneous activities of simultaneously recorded VC and LGN neurons revealed excitatory cortico-geniculate connections in 18 pairs with RFCs separated by less than 1.7 degrees. In 15 pairs the peak latency of the excitation was 2--5 msec (3.4 msec in the average), 3 pairs showed long cortico-geniculate latencies (13--18 msec). The existence of a fast and slow cortico-geniculate system is suggested. 3. Inhibitory cortico-geniculate interaction was demonstrated with cross-correlation analysis in 8 pairs of which 4 had RFCs separated by more than 1.7 degrees. The onset latency of the inhibition was 2--7 msec except for 2 pairs with about 20 msec latency. 4. Most of the LGN neurons which were affected by cortical glutamate application or which showed an excitatory or inhibitory connection with a VC neurons were sustained cells, while the majority of VC neurons which were recorded in the effective glutamate application sites or which showed a significant interaction with LGN neurons in the cross-correlogram were binocularly driven and complex, with mostly large RFCs (mean diameter 3.5 degrees). They responded briskly to moving small spots as well as to moving slits. 5. It is concluded that the corticofugal excitatory effect is transmitted through monosynaptic links from VC neurons located in layer VI (complex cell) to LGN relay neurons (mostly sustained-cell) and this system is organized in a precise topographical manner. 6. In an Appendix neuron pairs which showed a positive correlation in the geniculo-cortical direction were described. The findings may support the view that complex as well as simple cells are drive monosynaptically from geniculo-cortical afferents of the sustained or transient type."}
{"id": "PMID:210032", "title": "Vestibulo-ocular reflex from the posterior canal nerve to extraocular motoneurons in the cat.", "content": "In the anesthetized cat, the posterior canal nerve (PCN) was stimulated by electric pulses and synaptic responses were recorded intracellularly in the three antagonistic pairs of extraocular motoneurons. Pure reciprocal effects were obtained in the motoneurons innervating the antagonistic pair of ipsilateral oblique muscles and the antagonistic pair of contralateral vertical rectus muscles. These responses consisted of low threshold disynaptic excitatory postsynaptic potentials (EPSPs) in either the contralateral superior oblique (c--SO) (trochlear) or contralateral inferior rectus (c--IR) motoneurons and of disynaptic inhibitory postsynaptic potentials (IPSPs) in either the ipsilateral inferior oblique (i--IO) or ipsilateral superior rectus (i--SR) motoneurons. In addition, disynaptic IPSPs were also found in (i--SO) motoneurons. Mixtures of low threshold (di or trisynaptic) EPSPs and IPSPs were found in all other extraocular motoneurons except for the contralateral lateral rectus (c--LR) motoneurons. These results may afford a basis for the characteristic eye movements induced by vertical canal nerve stimulation.", "contents": "Vestibulo-ocular reflex from the posterior canal nerve to extraocular motoneurons in the cat. In the anesthetized cat, the posterior canal nerve (PCN) was stimulated by electric pulses and synaptic responses were recorded intracellularly in the three antagonistic pairs of extraocular motoneurons. Pure reciprocal effects were obtained in the motoneurons innervating the antagonistic pair of ipsilateral oblique muscles and the antagonistic pair of contralateral vertical rectus muscles. These responses consisted of low threshold disynaptic excitatory postsynaptic potentials (EPSPs) in either the contralateral superior oblique (c--SO) (trochlear) or contralateral inferior rectus (c--IR) motoneurons and of disynaptic inhibitory postsynaptic potentials (IPSPs) in either the ipsilateral inferior oblique (i--IO) or ipsilateral superior rectus (i--SR) motoneurons. In addition, disynaptic IPSPs were also found in (i--SO) motoneurons. Mixtures of low threshold (di or trisynaptic) EPSPs and IPSPs were found in all other extraocular motoneurons except for the contralateral lateral rectus (c--LR) motoneurons. These results may afford a basis for the characteristic eye movements induced by vertical canal nerve stimulation."}
{"id": "PMID:210048", "title": "Murine cytomegalovirus and fertility: potential sexual transmission and the effect of this virus on fertilization in vitro.", "content": "Male mice were inoculated with murine cytomegalovirus (MCMV) to produce an acute generalized infection. Infections virus was recovered from both epididymal sperm and seminal vesicles as well as from uterine sperm collected from mated females, suggesting that MCMV might be transmitted sexually. Because the presence of virus in the ejaculate might affect the fertilization process, the effect of MCMV on the fertilization of mouse gametes and on subsequent embryonic development was studied in vitro. Although the fertilization rate was reduced when sperm were preincubated with infectious virus, this was also the case when heat-inactivated virus was used, leading to the conclusion that this effect was not due to a direct infectious interaction between virus and gametes. Subsequent embryonic development was normal, and there was no evidence of productive infection of the preimplantation embryo.", "contents": "Murine cytomegalovirus and fertility: potential sexual transmission and the effect of this virus on fertilization in vitro. Male mice were inoculated with murine cytomegalovirus (MCMV) to produce an acute generalized infection. Infections virus was recovered from both epididymal sperm and seminal vesicles as well as from uterine sperm collected from mated females, suggesting that MCMV might be transmitted sexually. Because the presence of virus in the ejaculate might affect the fertilization process, the effect of MCMV on the fertilization of mouse gametes and on subsequent embryonic development was studied in vitro. Although the fertilization rate was reduced when sperm were preincubated with infectious virus, this was also the case when heat-inactivated virus was used, leading to the conclusion that this effect was not due to a direct infectious interaction between virus and gametes. Subsequent embryonic development was normal, and there was no evidence of productive infection of the preimplantation embryo."}
{"id": "PMID:210053", "title": "[Participation of thyrocalcitonin in the development of stress].", "content": "The immobilization stress in rats entailed raise of calcium content in the plasma followed by a decrease to the hypocalcaemic level. The thyrocalcitonin activity of plasma was undetectable in intact rats, but increased to 5 mU/ml after 3 hrs of stress. Administration of bovine thyrocalcitonin (10 U/100 g) before the immobilization inhibited the lowering of CRF activity of hypothalamic extracts, ACTH content of hypophysis, and ascorbic acid concentration in adrenal glands of the rats under stress, i.e. inhibited the development of stress reaction.", "contents": "[Participation of thyrocalcitonin in the development of stress]. The immobilization stress in rats entailed raise of calcium content in the plasma followed by a decrease to the hypocalcaemic level. The thyrocalcitonin activity of plasma was undetectable in intact rats, but increased to 5 mU/ml after 3 hrs of stress. Administration of bovine thyrocalcitonin (10 U/100 g) before the immobilization inhibited the lowering of CRF activity of hypothalamic extracts, ACTH content of hypophysis, and ascorbic acid concentration in adrenal glands of the rats under stress, i.e. inhibited the development of stress reaction."}
{"id": "PMID:210054", "title": "[Reactions of the microcirculatory bed of cat mesentery during exposure to heat].", "content": "The TV-microscopy in cats revealed that, by the 30th minute of 2-hr overheating, the arterioles are dilated and venules constricted. In the course of raise of body temperature from 36 degrees to 40 degrees C, the number of dilatory and constrictory responses of venules remains the same while the number of arteriole dilatory responses diminishes and of constrictory responses increases. At 40 degrees C of body temperature, the number of dilatory responses of the mesenteric arterioles and venules makes about 20--30% while the number of constrictory responses--70--80%. The extent of dilation of arterioles and venules increases with the heating while the extent of constriction, having achieved a certain level, starts to diminish. The greatest responses occurred in the microvessels with initial diameter 60 and more microns. The responses of microvessels with a lesser diameter could be different. The data obtained using hexonium, dihydroergotoxin, inderal, atropin, dezeril, methyamide, and tavegil, suggest participation of adrenergic and histamingergic substances in vasomotor responses of the microvessels to the hyperthermia.", "contents": "[Reactions of the microcirculatory bed of cat mesentery during exposure to heat]. The TV-microscopy in cats revealed that, by the 30th minute of 2-hr overheating, the arterioles are dilated and venules constricted. In the course of raise of body temperature from 36 degrees to 40 degrees C, the number of dilatory and constrictory responses of venules remains the same while the number of arteriole dilatory responses diminishes and of constrictory responses increases. At 40 degrees C of body temperature, the number of dilatory responses of the mesenteric arterioles and venules makes about 20--30% while the number of constrictory responses--70--80%. The extent of dilation of arterioles and venules increases with the heating while the extent of constriction, having achieved a certain level, starts to diminish. The greatest responses occurred in the microvessels with initial diameter 60 and more microns. The responses of microvessels with a lesser diameter could be different. The data obtained using hexonium, dihydroergotoxin, inderal, atropin, dezeril, methyamide, and tavegil, suggest participation of adrenergic and histamingergic substances in vasomotor responses of the microvessels to the hyperthermia."}
{"id": "PMID:210057", "title": "Cyclic AMP levels in isolated frog skin epithelium: effects of phosphodiesterase inhibitors, oxytocin and catecholamines.", "content": "Direct measurements of cyclic AMP were performed in the isolated epithelium of frog skin. Phosphodiesterase inhibitors (methylxanthines, papaverine) and activators of adenylyl cyclase (oxytocin, catecholamines) significantly increased the cyclic AMP content. Propranolol completely blocked the generation of cAMP induced by beta-adrenergic agonists but had little or no effect on that induced by oxytocin. Phentolamine enhanced the cAMP production by adrenalin and noradrenalin. At supramaximal concentrations, oxytocin and isoproterenol produced similar increments in cAMP, while exposure to both agents roughly doubled the increase in cAMP. The results suggest the presence of independent receptors for oxytocin and catecholamines in frog skin, with additive effects on cAMP generation.", "contents": "Cyclic AMP levels in isolated frog skin epithelium: effects of phosphodiesterase inhibitors, oxytocin and catecholamines. Direct measurements of cyclic AMP were performed in the isolated epithelium of frog skin. Phosphodiesterase inhibitors (methylxanthines, papaverine) and activators of adenylyl cyclase (oxytocin, catecholamines) significantly increased the cyclic AMP content. Propranolol completely blocked the generation of cAMP induced by beta-adrenergic agonists but had little or no effect on that induced by oxytocin. Phentolamine enhanced the cAMP production by adrenalin and noradrenalin. At supramaximal concentrations, oxytocin and isoproterenol produced similar increments in cAMP, while exposure to both agents roughly doubled the increase in cAMP. The results suggest the presence of independent receptors for oxytocin and catecholamines in frog skin, with additive effects on cAMP generation."}
{"id": "PMID:210058", "title": "Nuclear triiodothyronine receptors in the developing rat brain.", "content": "This study examines whether the high sensitivity of the developing brain to thyroid hormones and the purported decline in sensitivity in adulthood, are correlated with changes in the density and affinity characteristics of specific nuclear T3 receptors. The authors have found that the nuclei of cerebral hemispheres have a high density of T3 receptors at birth (212 +/-28 X 10(-17) mol/microgram DNA) which declines to adult levels by the end of the second postnatal week (115 +/- 7 X 10(-17) mol/microgram DNA), remaining at this level until 6 months of age. Even though no significant changes were detected in the equilibrium dissociation constant (Kd) during the early period of development, comparison neonatal with the adult brain reveals a decrease in Kd (neonatal, 3.9 X 10(-10) M; adult, 2.3 X 10(-10) M). In the developing animal, neonatal thyroidectomy increased the number of binding sites in the nucleus by 36--44%. It is concluded that the high number of nuclear T3 receptors in the first week of postnatal life is correlated with the high dependence of brain tissue on thyroid hormones and that the decline in brain sensitivity may be associated with the decline in nuclear T3 receptors. The high affinity and density of nuclear receptors in adult brain tissue relative to the developing brain and liver, respectively, point to a continued regulatory role of thyroid hormones in brain.", "contents": "Nuclear triiodothyronine receptors in the developing rat brain. This study examines whether the high sensitivity of the developing brain to thyroid hormones and the purported decline in sensitivity in adulthood, are correlated with changes in the density and affinity characteristics of specific nuclear T3 receptors. The authors have found that the nuclei of cerebral hemispheres have a high density of T3 receptors at birth (212 +/-28 X 10(-17) mol/microgram DNA) which declines to adult levels by the end of the second postnatal week (115 +/- 7 X 10(-17) mol/microgram DNA), remaining at this level until 6 months of age. Even though no significant changes were detected in the equilibrium dissociation constant (Kd) during the early period of development, comparison neonatal with the adult brain reveals a decrease in Kd (neonatal, 3.9 X 10(-10) M; adult, 2.3 X 10(-10) M). In the developing animal, neonatal thyroidectomy increased the number of binding sites in the nucleus by 36--44%. It is concluded that the high number of nuclear T3 receptors in the first week of postnatal life is correlated with the high dependence of brain tissue on thyroid hormones and that the decline in brain sensitivity may be associated with the decline in nuclear T3 receptors. The high affinity and density of nuclear receptors in adult brain tissue relative to the developing brain and liver, respectively, point to a continued regulatory role of thyroid hormones in brain."}
{"id": "PMID:210059", "title": "HCG-induced changes in the number of rat testis LH/HCG receptors.", "content": "Adult male rats were injected subcutaneously with a mixture of hCG and [125I]hCG (3, 5, 10, 100 or 1000 IU), and killed 3, 6, 16, 24 or 48 h after injection. Specific uptake of [125I]hCG by the testes as well as the remaining in vitro binding capacity were measured. Cycloheximide (1.5 mg/kg) was given together with hCG to another group of animals. The effect of hCG on testicular LH/hCG receptors was found to consist of two phases: first, 6--16 h after injection, a significant increase in the binding capacity occurred, which was found with the lower 3--10 IU doses of hCG. Thereafter there was a pronounced decrease in receptor concentration, which was directly correlated to the dose of hCG. Experiments with cycloheximide suggest that the decrease in binding, but not the increase, is at least partly dependent on protein synthesis.", "contents": "HCG-induced changes in the number of rat testis LH/HCG receptors. Adult male rats were injected subcutaneously with a mixture of hCG and [125I]hCG (3, 5, 10, 100 or 1000 IU), and killed 3, 6, 16, 24 or 48 h after injection. Specific uptake of [125I]hCG by the testes as well as the remaining in vitro binding capacity were measured. Cycloheximide (1.5 mg/kg) was given together with hCG to another group of animals. The effect of hCG on testicular LH/hCG receptors was found to consist of two phases: first, 6--16 h after injection, a significant increase in the binding capacity occurred, which was found with the lower 3--10 IU doses of hCG. Thereafter there was a pronounced decrease in receptor concentration, which was directly correlated to the dose of hCG. Experiments with cycloheximide suggest that the decrease in binding, but not the increase, is at least partly dependent on protein synthesis."}
{"id": "PMID:210060", "title": "Comparison of alpha-ketoisocaproic acid and glucose in rats: effects on insulin and somatostatin release and on islet cAMP content.", "content": "The insulinotropic effects of alpha-ketoisocaproic acid and glucose reveal many common characteristics in vivo and in vitro. They qualify as initiators of insulin release, their action is amplified by potentiators of insulin release, and they have a similar potency at equimolar concentrations. The dynamics of insulin release evoked by alpha-ketoisocaproic acid and glucose are similar. Epinephrine completely inhibits the insulinotropic effect of glucose and alpha-ketoisocaproic acid. Mannoheptulose exhibits a complete, immediate and reversible blockade of glucose-induced insulin release. In contrast, inhibition of alpha-ketoisocaproic acid-induced insulin release occurs after a lag period and is not reversed by removal of the inhibitor. alpha-ketoisocaproic acid, at equimolar concentrations, is several-fold more effective than glucose in elevating cAMP content in islet. alpha ketoisocaproic acid and glucose are about equally effective in stimulating somatostatin release from isolated rat pancreatic islets. This stimulation is inhibited by epinephrine. Mannoheptulose inhibits only somatostatin release induced by glucose but not by alpha-ketoisocaproic acid. It suggested that the insulinotropic characteristics of glucose and alpha-ketoisocaproic acid reveal many common features, while their mode of action appears to be different.", "contents": "Comparison of alpha-ketoisocaproic acid and glucose in rats: effects on insulin and somatostatin release and on islet cAMP content. The insulinotropic effects of alpha-ketoisocaproic acid and glucose reveal many common characteristics in vivo and in vitro. They qualify as initiators of insulin release, their action is amplified by potentiators of insulin release, and they have a similar potency at equimolar concentrations. The dynamics of insulin release evoked by alpha-ketoisocaproic acid and glucose are similar. Epinephrine completely inhibits the insulinotropic effect of glucose and alpha-ketoisocaproic acid. Mannoheptulose exhibits a complete, immediate and reversible blockade of glucose-induced insulin release. In contrast, inhibition of alpha-ketoisocaproic acid-induced insulin release occurs after a lag period and is not reversed by removal of the inhibitor. alpha-ketoisocaproic acid, at equimolar concentrations, is several-fold more effective than glucose in elevating cAMP content in islet. alpha ketoisocaproic acid and glucose are about equally effective in stimulating somatostatin release from isolated rat pancreatic islets. This stimulation is inhibited by epinephrine. Mannoheptulose inhibits only somatostatin release induced by glucose but not by alpha-ketoisocaproic acid. It suggested that the insulinotropic characteristics of glucose and alpha-ketoisocaproic acid reveal many common features, while their mode of action appears to be different."}
{"id": "PMID:210061", "title": "LH-RH binding to purified pituitary plasma membranes: absence of adenylate cyclase activation.", "content": "Purified bovine pituitary plasma membranes possess two specific LH-RH binding sites. The high affinity site (2.5 X 10(9) l/mol) has low capacity (9 X 10(-15) mol/mg membrane protein) while the low affinity site 6.1 X 10(5) l/mol) has a much higher capacity (1.1 X 10(-10) mol/mg). Specific LH-RH binding to plasma membranes is increased 8.5-fold during purification from homogenate whilst adenylate cyclase activity is enriched 7--8-fold. Distribution of specific LH-RH binding to sucrose density gradient interface fractions parallels that of adenylate cyclase activity. Mg2+ and Ca2+ inhibit specific [125I]LH-RH binding at micromolar concentrations. Synthetic LH-RH, up to 250 microgram/ml, failed to stimulate adenylase cyclase activity of the purified bovine membranes. Using a crude 10,800 g rat pituitary membrane preparation, LH-RH similarly failed to activate adenylate cyclase even in the presence of guanyl nucleotides. These data confirm the presence of LH-RH receptor sites on pituitary plasma membranes and suggest that LH-RH-induced gonadotrophin release may be mediated by mechanisms other than activation of adenylate cyclase.", "contents": "LH-RH binding to purified pituitary plasma membranes: absence of adenylate cyclase activation. Purified bovine pituitary plasma membranes possess two specific LH-RH binding sites. The high affinity site (2.5 X 10(9) l/mol) has low capacity (9 X 10(-15) mol/mg membrane protein) while the low affinity site 6.1 X 10(5) l/mol) has a much higher capacity (1.1 X 10(-10) mol/mg). Specific LH-RH binding to plasma membranes is increased 8.5-fold during purification from homogenate whilst adenylate cyclase activity is enriched 7--8-fold. Distribution of specific LH-RH binding to sucrose density gradient interface fractions parallels that of adenylate cyclase activity. Mg2+ and Ca2+ inhibit specific [125I]LH-RH binding at micromolar concentrations. Synthetic LH-RH, up to 250 microgram/ml, failed to stimulate adenylase cyclase activity of the purified bovine membranes. Using a crude 10,800 g rat pituitary membrane preparation, LH-RH similarly failed to activate adenylate cyclase even in the presence of guanyl nucleotides. These data confirm the presence of LH-RH receptor sites on pituitary plasma membranes and suggest that LH-RH-induced gonadotrophin release may be mediated by mechanisms other than activation of adenylate cyclase."}
{"id": "PMID:210062", "title": "Receptor regulation and target cell responses: studies in the ovarian luteal cell.", "content": "Studies of hormone-induced 'desensitization' in the luteinized rat ovary show that changes in receptor number and adenylate cyclase at the cell surface result in an altered biological effect of luteinizing hormone on progesterone production. The sensitivity of these effects to changes in gonadotropin levels suggests that receptor turnover or processing is involved in the normal mechanism of hormone action.", "contents": "Receptor regulation and target cell responses: studies in the ovarian luteal cell. Studies of hormone-induced 'desensitization' in the luteinized rat ovary show that changes in receptor number and adenylate cyclase at the cell surface result in an altered biological effect of luteinizing hormone on progesterone production. The sensitivity of these effects to changes in gonadotropin levels suggests that receptor turnover or processing is involved in the normal mechanism of hormone action."}
{"id": "PMID:210068", "title": "Topographical studies on histamine- and adrenaline-sensitive adenylate cyclases in gastric and duodenal mucosa of human beings.", "content": "The distribution of histamine- and catecholamine-sensitive adenylate cyclases in human gastric and duodenal mucosa was studied. Basal enzyme activities averaged 155 pmol cAMP/mg prot./15 min in fundic gastric mucosa, 305 pmol cAMP/mg prot./15 min in the antral and 344 pmol cAMP/mg prot./15 min duodenal mucosa. 1 mM histamine induced a more than 2-fold increase of enzyme activity in fundic homogenates, whereas this secretagogue was nearly ineffective in similar preparations from the antral region (1.2-fold increase of enzyme activity). The response towards adrenaline was virtually identical in fundic and antral mucosa preparations. The duodenal enzyme was insensitive toward this catecholamine as well as to histamine. The data are suggestive for a messenger function of cAMP in histamine-stimulated gastric acid secretion.", "contents": "Topographical studies on histamine- and adrenaline-sensitive adenylate cyclases in gastric and duodenal mucosa of human beings. The distribution of histamine- and catecholamine-sensitive adenylate cyclases in human gastric and duodenal mucosa was studied. Basal enzyme activities averaged 155 pmol cAMP/mg prot./15 min in fundic gastric mucosa, 305 pmol cAMP/mg prot./15 min in the antral and 344 pmol cAMP/mg prot./15 min duodenal mucosa. 1 mM histamine induced a more than 2-fold increase of enzyme activity in fundic homogenates, whereas this secretagogue was nearly ineffective in similar preparations from the antral region (1.2-fold increase of enzyme activity). The response towards adrenaline was virtually identical in fundic and antral mucosa preparations. The duodenal enzyme was insensitive toward this catecholamine as well as to histamine. The data are suggestive for a messenger function of cAMP in histamine-stimulated gastric acid secretion."}
{"id": "PMID:210063", "title": "Effect of the association time of in vivo bound prolactin on the [125I]prolactin receptor assays of female rat livers.", "content": "Significantly (P less than 0.01) reduced 125I-labeled ovine prolactin binding (mean, --22%), as a result of an ether anesthesia-reduced rise in serum prolactin, was observed in plasma membrane preparations of liver samples of female rats taken after 5 min of etherization when compared to samples taken from the same animals during the first minute of etherization. This reduction in assayable receptors occurred after 1 h but not 2 h of assay incubation time. Significantly (P less than 0.05) reduced 125I-labeled ovine prolactin binding (mean, --16%) was also observed in liver samples exposed to a 30-min ether-induced rise in serum prolactin when compared to liver samples taken during the first minute of etherization. In contrast, this reduction was apparent at assay incubation times of 1, 2 and 4 h but not at 10 h. These results suggest that serum prolactin can bind to prolactin receptors in vivo and partially block subsequent 125I-labeled ovine prolactin receptor assay. In addition, these data provide evidence that a complex time-dependent binding of prolactin may occur in the plasma of the female rat liver.", "contents": "Effect of the association time of in vivo bound prolactin on the [125I]prolactin receptor assays of female rat livers. Significantly (P less than 0.01) reduced 125I-labeled ovine prolactin binding (mean, --22%), as a result of an ether anesthesia-reduced rise in serum prolactin, was observed in plasma membrane preparations of liver samples of female rats taken after 5 min of etherization when compared to samples taken from the same animals during the first minute of etherization. This reduction in assayable receptors occurred after 1 h but not 2 h of assay incubation time. Significantly (P less than 0.05) reduced 125I-labeled ovine prolactin binding (mean, --16%) was also observed in liver samples exposed to a 30-min ether-induced rise in serum prolactin when compared to liver samples taken during the first minute of etherization. In contrast, this reduction was apparent at assay incubation times of 1, 2 and 4 h but not at 10 h. These results suggest that serum prolactin can bind to prolactin receptors in vivo and partially block subsequent 125I-labeled ovine prolactin receptor assay. In addition, these data provide evidence that a complex time-dependent binding of prolactin may occur in the plasma of the female rat liver."}
{"id": "PMID:210069", "title": "Evidence of agar gel electrophoresis changes of lipoprotein-X after phospholipase A and deoxycholic acid.", "content": "The effect of phospholipase A from snake venom and deoxycholic acid on lipoprotein-X (LP-X) recovered from the cathode side of a previous agar gel electrophoresis is described. Adding phospholipase A and deoxycholic acid to the removed cathodal fraction is followed by a marked migration to the anode side on a second electrophoresis procedure. This seems to confirm that phospholipase A and bile salts on LP-X particles modifying their agar gel electrophoretic migration characteristics.", "contents": "Evidence of agar gel electrophoresis changes of lipoprotein-X after phospholipase A and deoxycholic acid. The effect of phospholipase A from snake venom and deoxycholic acid on lipoprotein-X (LP-X) recovered from the cathode side of a previous agar gel electrophoresis is described. Adding phospholipase A and deoxycholic acid to the removed cathodal fraction is followed by a marked migration to the anode side on a second electrophoresis procedure. This seems to confirm that phospholipase A and bile salts on LP-X particles modifying their agar gel electrophoretic migration characteristics."}
{"id": "PMID:210064", "title": "Rat testis LH/hCG recptors and testosterone production after treatment with GnRH.", "content": "Adults male rats were implanted subcutaneously for 1, 2 or 4 days with Alzet osmotic minipumps, infusing synthetic gonadotropin-releasing hormone (GnRH) at a rate of 0.1 microgram/h. Plasma LH increased significantly, reaching a maximum after 2 days treatment. Plasma and testicular testosterone levels increased to a maximum in 1 day, and decreased gradually thereafter, reaching the control level by day 4. Testicular specific [125I]hCG binding decreased gradually during the treatment, being 57% of the controls by day 4. It is concluded that changes of physiologic magnitude in circulatory LH are able to induce a significant loss of testicular LH/hCG binding capacity. Furthermore, after a short stimulatory phase there is a lack of response in testicular steroidogenesis to the elevated LH levels.", "contents": "Rat testis LH/hCG recptors and testosterone production after treatment with GnRH. Adults male rats were implanted subcutaneously for 1, 2 or 4 days with Alzet osmotic minipumps, infusing synthetic gonadotropin-releasing hormone (GnRH) at a rate of 0.1 microgram/h. Plasma LH increased significantly, reaching a maximum after 2 days treatment. Plasma and testicular testosterone levels increased to a maximum in 1 day, and decreased gradually thereafter, reaching the control level by day 4. Testicular specific [125I]hCG binding decreased gradually during the treatment, being 57% of the controls by day 4. It is concluded that changes of physiologic magnitude in circulatory LH are able to induce a significant loss of testicular LH/hCG binding capacity. Furthermore, after a short stimulatory phase there is a lack of response in testicular steroidogenesis to the elevated LH levels."}
{"id": "PMID:210065", "title": "Physicochemical properties of the cytoplasmic triiodothyronine binding protein from tadpole liver and tail fin.", "content": "The sedimentation velocity, gel filtration properties and pattern of elution from ion exchange gels of the cytoplasmic triiodothyronine (T3) binding protein from Rana catesbeiana liver and tail fin cytosol were determined. The T3 binding protein in liver cytosol had a sedimentation coefficient of 4.4S on sucrose gradients and a Stokes radius from Sephadex gel filtration of 38.2 +/- 4.2 A. From these two values a molecular weight of 71,700 +/- 4,100 and a frictional ratio of 1.28 +/- 0.05 for the T3 binding protein from tadpole liver has been calculated. The liver T3 binding protein was eluted from DEAE--Sephadex gels at a salt concentration of 0.233 +/- 0.017 M NaCl. The sedimentation coefficient, Stokes radius and salt requirement for elution from DEAE--Sephadex of the T3 binding protein from tail fin cytosol were essentially identical (4.4S, 35.2 +/- 4.2 A, nd 0.213 +/- 0.015 M NaCl respectively. The calculated molecular weight is 66,100 +/- 7,900 and the frictional ratio is 1.21 +/- 0.10 for for the tail fin T3 binding protein. The great similarity in the physicochemical properties of the T3 binding protein from the liver and tail fin implies that the T3 binding protein in each tissue is similar if not identical. The possible reason for the differences in the dissociation constants previously reported for the binding of T3 in the two tissues is discussed.", "contents": "Physicochemical properties of the cytoplasmic triiodothyronine binding protein from tadpole liver and tail fin. The sedimentation velocity, gel filtration properties and pattern of elution from ion exchange gels of the cytoplasmic triiodothyronine (T3) binding protein from Rana catesbeiana liver and tail fin cytosol were determined. The T3 binding protein in liver cytosol had a sedimentation coefficient of 4.4S on sucrose gradients and a Stokes radius from Sephadex gel filtration of 38.2 +/- 4.2 A. From these two values a molecular weight of 71,700 +/- 4,100 and a frictional ratio of 1.28 +/- 0.05 for the T3 binding protein from tadpole liver has been calculated. The liver T3 binding protein was eluted from DEAE--Sephadex gels at a salt concentration of 0.233 +/- 0.017 M NaCl. The sedimentation coefficient, Stokes radius and salt requirement for elution from DEAE--Sephadex of the T3 binding protein from tail fin cytosol were essentially identical (4.4S, 35.2 +/- 4.2 A, nd 0.213 +/- 0.015 M NaCl respectively. The calculated molecular weight is 66,100 +/- 7,900 and the frictional ratio is 1.21 +/- 0.10 for for the tail fin T3 binding protein. The great similarity in the physicochemical properties of the T3 binding protein from the liver and tail fin implies that the T3 binding protein in each tissue is similar if not identical. The possible reason for the differences in the dissociation constants previously reported for the binding of T3 in the two tissues is discussed."}
{"id": "PMID:210070", "title": "Lecithin: cholesterol acyltransferase activity in patients with chronic liver diseases and positive LP-X tests.", "content": "Lecithin: cholesterol acyltransferase activity has been measured in serum from patients with various liver disorders and positive LP-X tests and from healthy subjects. Statistical analysis indicated that lecithin: cholesterol acyltransferase activity provided no help in the discrimination between the persons of both groups although the mean activities differed significantly.", "contents": "Lecithin: cholesterol acyltransferase activity in patients with chronic liver diseases and positive LP-X tests. Lecithin: cholesterol acyltransferase activity has been measured in serum from patients with various liver disorders and positive LP-X tests and from healthy subjects. Statistical analysis indicated that lecithin: cholesterol acyltransferase activity provided no help in the discrimination between the persons of both groups although the mean activities differed significantly."}
{"id": "PMID:210074", "title": "Sensitivity difference of rat ascites hepatoma AH-13 and mouse leukemia L-1210 to nitrosourea derivatives.", "content": "The structure-activity relationship in different sensitivity of AH-13 and L-1210 to nitrosourea nad related derivatives was examined. N-Methyl-N-nitrosoureido derivatives, such as 1-methyl-1-nitrosourea (MNU) and 1, 1'-polymethylene-bis(3-substituted 3-nitrosourea), were inactive against AH-13 and slightly active against L-1210. On the contrary, 1, 1'-polymethylene-bis(3-substituted 1-nitrourea) derivatives were more active against AH-13 than against L-1210. The nitrosoureas which had bis(2-chloroethyl) group at the terminal were highly active against AH-13 and L-1210. One of denitrosated derivatives, 1, 1'-ethylene-bis[3-(2-chloroethyl)urea], was active against AH-13 alone. In addition, diisocyanates, nitrourea, ammonium carbamate, and 1-methyl-1-nitrourea, which are related to the nitrosourea compounds, were also tested for their activity against AH-13 and L-1210. Diisocyanates and nitrourea were active against AH-13 alone, while other compounds were all inactive.", "contents": "Sensitivity difference of rat ascites hepatoma AH-13 and mouse leukemia L-1210 to nitrosourea derivatives. The structure-activity relationship in different sensitivity of AH-13 and L-1210 to nitrosourea nad related derivatives was examined. N-Methyl-N-nitrosoureido derivatives, such as 1-methyl-1-nitrosourea (MNU) and 1, 1'-polymethylene-bis(3-substituted 3-nitrosourea), were inactive against AH-13 and slightly active against L-1210. On the contrary, 1, 1'-polymethylene-bis(3-substituted 1-nitrourea) derivatives were more active against AH-13 than against L-1210. The nitrosoureas which had bis(2-chloroethyl) group at the terminal were highly active against AH-13 and L-1210. One of denitrosated derivatives, 1, 1'-ethylene-bis[3-(2-chloroethyl)urea], was active against AH-13 alone. In addition, diisocyanates, nitrourea, ammonium carbamate, and 1-methyl-1-nitrourea, which are related to the nitrosourea compounds, were also tested for their activity against AH-13 and L-1210. Diisocyanates and nitrourea were active against AH-13 alone, while other compounds were all inactive."}
{"id": "PMID:210075", "title": "Detection of Epstein-Barr virus in biopsied malignant lymphoma cell and its continuous culture.", "content": "In more than 80% of tumor cells in the pericardiac effusion of a case of malignant B-cell lymphoma, Epstein-Barr virus-determined nuclear antigen (EBNA) was detected by the anticomplement immunofluorescence test. Moreover, herpestype virus particles, although few in number, were demonstrated in the nucleus of lymphoma cells by an electron microscope. Tumor cells in the pericardiac effusion were seeded at 98% purity after centrifugation on Ficoll-Conray and, soon after plating, they proliferated continuously without any lag phase of growth or cell death. Therefore, the established cell line was regarded as of tumor cell origin and named Fujimaki-II cell after patient's name. On the other hand, Fujimaki-I cells were established from the biopsied tumor in the same way. These two cell lines, B-lymphocyte in nature, had both EB virus-related antigens and herpes-types virus particles. Heterotransplantation of cultured cells and tumor tissue obtained at autopsy into athymic nude mice was not successful. Transformation of cord blood lymphocytes by the virus released from Fujimaki-II cell also failed. This might be the first case of non-Burkitt type lymphoma in which the EB virus genome was directly detected in the tumor cells.", "contents": "Detection of Epstein-Barr virus in biopsied malignant lymphoma cell and its continuous culture. In more than 80% of tumor cells in the pericardiac effusion of a case of malignant B-cell lymphoma, Epstein-Barr virus-determined nuclear antigen (EBNA) was detected by the anticomplement immunofluorescence test. Moreover, herpestype virus particles, although few in number, were demonstrated in the nucleus of lymphoma cells by an electron microscope. Tumor cells in the pericardiac effusion were seeded at 98% purity after centrifugation on Ficoll-Conray and, soon after plating, they proliferated continuously without any lag phase of growth or cell death. Therefore, the established cell line was regarded as of tumor cell origin and named Fujimaki-II cell after patient's name. On the other hand, Fujimaki-I cells were established from the biopsied tumor in the same way. These two cell lines, B-lymphocyte in nature, had both EB virus-related antigens and herpes-types virus particles. Heterotransplantation of cultured cells and tumor tissue obtained at autopsy into athymic nude mice was not successful. Transformation of cord blood lymphocytes by the virus released from Fujimaki-II cell also failed. This might be the first case of non-Burkitt type lymphoma in which the EB virus genome was directly detected in the tumor cells."}
{"id": "PMID:210076", "title": "Mesotheliomas induced by sterigmatocystin in Wistar rats.", "content": "Male Wistar rats were given repeated injections of sterigmatocystin (stg) and related compounds into the peritoneal cavity once a week for 23 weeks. Only stg alone produced mesothelioma in 20 of 40 rats given a total dose of 20 approximately 25 mg, while no mesotheliomas were found in rats injected O-acetyl-stg (AcO-stg) and dihydro-stg. There were two histological types in the mesothelioma induced by stg; the epithelioid and mesenchymal types. There was little loose connective tissue between the epithelioid cell tumors, whereas abundant dense collagen fibers were found between the cell nests of the mesenchymal cell types of mesothelioma. The hepatocellular carcinomas were found in a rat treated with stg and in five animals given AcO-stg. The fact that mesotheliomas could be induced in high incidence by direct intraperitoneal application of stg suggests a potent carcinogenicity of stg. Although both dihydro-stg and stg formed fine needle-like crystals when injected into the peritoneal cavity, dihydro-stg could not produce any mesothelioma. Dihydro-stg, reduction product of stg, has no double bond in the terminal furan ring. Therefore, the carcinogenicity of stg may be related more closely with the presence of a double bond in the terminal furan ring of stg than the physical form in the peritoneal cavity. AcO-stg may easily be absorbed from the peritoneum, so that it could not persist in the peritoneium for sufficient duration for carcinogenesis.", "contents": "Mesotheliomas induced by sterigmatocystin in Wistar rats. Male Wistar rats were given repeated injections of sterigmatocystin (stg) and related compounds into the peritoneal cavity once a week for 23 weeks. Only stg alone produced mesothelioma in 20 of 40 rats given a total dose of 20 approximately 25 mg, while no mesotheliomas were found in rats injected O-acetyl-stg (AcO-stg) and dihydro-stg. There were two histological types in the mesothelioma induced by stg; the epithelioid and mesenchymal types. There was little loose connective tissue between the epithelioid cell tumors, whereas abundant dense collagen fibers were found between the cell nests of the mesenchymal cell types of mesothelioma. The hepatocellular carcinomas were found in a rat treated with stg and in five animals given AcO-stg. The fact that mesotheliomas could be induced in high incidence by direct intraperitoneal application of stg suggests a potent carcinogenicity of stg. Although both dihydro-stg and stg formed fine needle-like crystals when injected into the peritoneal cavity, dihydro-stg could not produce any mesothelioma. Dihydro-stg, reduction product of stg, has no double bond in the terminal furan ring. Therefore, the carcinogenicity of stg may be related more closely with the presence of a double bond in the terminal furan ring of stg than the physical form in the peritoneal cavity. AcO-stg may easily be absorbed from the peritoneum, so that it could not persist in the peritoneium for sufficient duration for carcinogenesis."}
{"id": "PMID:210077", "title": "Lysosomal accumulation of gallium-67 in Morris hepatoma-7316A and Shionogi mammary carcinoma-115.", "content": "Intracellular localization of gallium-67 was investigated in Morris hepatoma-7316A and Shionogi mammary carcinoma-115 cells by the cell fractionation method 48 hr after an intraperitoneal injection of the nuclide. When lysosomes were purified from both tumors by discontinuous sucrose density gradient centrifugation, they had a strikingly high relative specific activity of the nuclide. From these results it was confirmed that gallium-67 is concentrated most specifically in the lysosomes of both tumor cells, which consist chiefly of phagolysosomes and can engulf only limited amount of foreign materials such as Triton and gallium-67.", "contents": "Lysosomal accumulation of gallium-67 in Morris hepatoma-7316A and Shionogi mammary carcinoma-115. Intracellular localization of gallium-67 was investigated in Morris hepatoma-7316A and Shionogi mammary carcinoma-115 cells by the cell fractionation method 48 hr after an intraperitoneal injection of the nuclide. When lysosomes were purified from both tumors by discontinuous sucrose density gradient centrifugation, they had a strikingly high relative specific activity of the nuclide. From these results it was confirmed that gallium-67 is concentrated most specifically in the lysosomes of both tumor cells, which consist chiefly of phagolysosomes and can engulf only limited amount of foreign materials such as Triton and gallium-67."}
{"id": "PMID:210078", "title": "Motility of rat ascites hepatoma cells, with reference to malignant characteristics in cancer metastasis.", "content": "The motility of four strains of rat ascites tumor cells in an agar medium was studied quantitatively by means of time lapse cinematography. The motility of these cells differed characteristically with each strain. Yoshida sarcoma and AH-66F cells showed active locomotion and partial movement markedly, while AH-130 and AH-100B cells made no locomotion and only a slight movement.", "contents": "Motility of rat ascites hepatoma cells, with reference to malignant characteristics in cancer metastasis. The motility of four strains of rat ascites tumor cells in an agar medium was studied quantitatively by means of time lapse cinematography. The motility of these cells differed characteristically with each strain. Yoshida sarcoma and AH-66F cells showed active locomotion and partial movement markedly, while AH-130 and AH-100B cells made no locomotion and only a slight movement."}
{"id": "PMID:210079", "title": "Comparison of carcinogenicity of N-alkyl-N'-nitro-N-nitroso-guanidines.", "content": "Carcinogenicity of seven homologs of N-alkyl-N'-nitrosoguanidine (N-alkyl-NNG), namely, N-methyl-NNG, N-propyl-NNG, N-butyl-NNG, N-isobutyl-NNG, N-pentyl-NNG, and N-hexyl-NNG, was examined by injecting the compounds subcutaneously into rats. All of them except N-isobutyl-NNG and N-hexyl-NNG were carcinogenic, but N-ethyl-NNG followed by N-methyl-NNG were stronger carcinogens than those with longer alkyl chains.", "contents": "Comparison of carcinogenicity of N-alkyl-N'-nitro-N-nitroso-guanidines. Carcinogenicity of seven homologs of N-alkyl-N'-nitrosoguanidine (N-alkyl-NNG), namely, N-methyl-NNG, N-propyl-NNG, N-butyl-NNG, N-isobutyl-NNG, N-pentyl-NNG, and N-hexyl-NNG, was examined by injecting the compounds subcutaneously into rats. All of them except N-isobutyl-NNG and N-hexyl-NNG were carcinogenic, but N-ethyl-NNG followed by N-methyl-NNG were stronger carcinogens than those with longer alkyl chains."}
{"id": "PMID:210081", "title": "Adenocarcinoma in tubular duplication of the sigmoid colon.", "content": "A rare case of mucus-secreting adenocarcinoma in a tubular duplication of the sigmoid colon is presented. The pertinent radiographic manifestations were: a calcium containing soft tissue mass located at the blind end of a 20 cm barium filled tubular duplication originating at the sigmoid colon.", "contents": "Adenocarcinoma in tubular duplication of the sigmoid colon. A rare case of mucus-secreting adenocarcinoma in a tubular duplication of the sigmoid colon is presented. The pertinent radiographic manifestations were: a calcium containing soft tissue mass located at the blind end of a 20 cm barium filled tubular duplication originating at the sigmoid colon."}
{"id": "PMID:210082", "title": "Benign hepatic lesions in women taking oral contraceptives.", "content": "Four previously unreported cases of benign hepatic cell lesions in young women taking oral contraceptives are described. A brief review of the literature is presented with emphasis on the clinical symptoms, the findings on angiography and radionuclide scan, and the relation of the lesions to oral contraceptives.", "contents": "Benign hepatic lesions in women taking oral contraceptives. Four previously unreported cases of benign hepatic cell lesions in young women taking oral contraceptives are described. A brief review of the literature is presented with emphasis on the clinical symptoms, the findings on angiography and radionuclide scan, and the relation of the lesions to oral contraceptives."}
{"id": "PMID:210083", "title": "Endotoxin and the liver. III. Modification of acute carbon tetrachloride injury by polymyxin b--an antiendotoxin.", "content": "Previous work suggests that endotoxin of enteric origin may contribute to both acute and chronic liver injury by other agents. In particular, evidence exists that endotoxin tolerance modifies biochemical and histological evidence of carbon tetrachloride hepatotoxicity. The present study was undertaken to ascertain whether another method of modifying endotoxicity would protect against carbon tetrachloride (CCl4) damage as well. The antibiotic polymyxin B (PB) has unique antiendotoxin properties not shared by gentamicin sulfate, an antibiotic with a similar antibacterial spectrum. In groups of rats pretreated with either PB, gentamicin, or diluent, the LD100 of an oral dose of CCl4 was reduced by PB to an LD50, but the gentamicin pretreatment was without effect. When a sublethal dose of CCl4 was administered, both the SGOT and SGPT values were significantly lower in the PB group of rats. This biochemical protection was mirrored in the striking lack of histological liver necrosis in these animals, protection not shared by the gentamicin group or controls. The incidence of endotoxemia 24 hr after CCl4 as detected by lead acetate enhancement was also reduced by PB pretreatment. These findings further support the contention that endotoxins from the gut may be major contributors to the extent of liver injury induced by an unrelated toxin.", "contents": "Endotoxin and the liver. III. Modification of acute carbon tetrachloride injury by polymyxin b--an antiendotoxin. Previous work suggests that endotoxin of enteric origin may contribute to both acute and chronic liver injury by other agents. In particular, evidence exists that endotoxin tolerance modifies biochemical and histological evidence of carbon tetrachloride hepatotoxicity. The present study was undertaken to ascertain whether another method of modifying endotoxicity would protect against carbon tetrachloride (CCl4) damage as well. The antibiotic polymyxin B (PB) has unique antiendotoxin properties not shared by gentamicin sulfate, an antibiotic with a similar antibacterial spectrum. In groups of rats pretreated with either PB, gentamicin, or diluent, the LD100 of an oral dose of CCl4 was reduced by PB to an LD50, but the gentamicin pretreatment was without effect. When a sublethal dose of CCl4 was administered, both the SGOT and SGPT values were significantly lower in the PB group of rats. This biochemical protection was mirrored in the striking lack of histological liver necrosis in these animals, protection not shared by the gentamicin group or controls. The incidence of endotoxemia 24 hr after CCl4 as detected by lead acetate enhancement was also reduced by PB pretreatment. These findings further support the contention that endotoxins from the gut may be major contributors to the extent of liver injury induced by an unrelated toxin."}
{"id": "PMID:210084", "title": "Augmentation of uridine diphosphate glucuronyltransferase activity in rat liver by adenosine 3',5'-monophosphate.", "content": "The role of cyclic adenosine 3',5'-monophosphate (cAMP) in the regulation of rat liver bilirubin uridine diphosphate glucuronyltransferase (UDP-GT) was studied. Augmentation of UDP-GT activity was obtained by cAMP, but not by 3'-AMP. A single administration of glucagon initiated a rapid but limited increase in enzyme activity, which reached a maximum after 2 hr. Similar augmentation of the hepatic enzyme was produced by injection of N6,O2-dibutyryl cAMP. The nucleotide is the mediator for UDP-GT augmentation by glucagon. The injection of glucagon led within 20 min to a 40-fold increase in the concentration of cAMP. The augmentation of UDP-GT activity by glucagon or dibutyryl cAMP was fully inhibited by actinomycin D. A second stimulation of liver by glucagon or dibutyryl cAMP 4 hr after the first injection, produced a new increase of UDP-GT activity.", "contents": "Augmentation of uridine diphosphate glucuronyltransferase activity in rat liver by adenosine 3',5'-monophosphate. The role of cyclic adenosine 3',5'-monophosphate (cAMP) in the regulation of rat liver bilirubin uridine diphosphate glucuronyltransferase (UDP-GT) was studied. Augmentation of UDP-GT activity was obtained by cAMP, but not by 3'-AMP. A single administration of glucagon initiated a rapid but limited increase in enzyme activity, which reached a maximum after 2 hr. Similar augmentation of the hepatic enzyme was produced by injection of N6,O2-dibutyryl cAMP. The nucleotide is the mediator for UDP-GT augmentation by glucagon. The injection of glucagon led within 20 min to a 40-fold increase in the concentration of cAMP. The augmentation of UDP-GT activity by glucagon or dibutyryl cAMP was fully inhibited by actinomycin D. A second stimulation of liver by glucagon or dibutyryl cAMP 4 hr after the first injection, produced a new increase of UDP-GT activity."}
{"id": "PMID:210085", "title": "[Estrogen therapy and carcinoma of the endometrium (author's transl)].", "content": "The public discussion and the discussion among gynaecologists about the possible increased risk to develop carcinoma of the endometrium following post menopausal treatment with estrogens has lead to insecurity and restricted attitudes in the prescriptions of estrogens. In a statistic comparison of matched pairs of 130 cases of carcinoma of the endometrium with an equal number of selected control cases the following findings were elucidated: 1. Any estrogen preparations do not increase the relative risk for the development of carcinoma of the endometrium. 2. Differentiation into conjugated estrogens, estriol, oral contraceptives and various other estrogen compounds showed a similar trend. 3. Estrogen-androgen compounds and estrodiol compounds did not increase the relative risk for endometrial carcinoma. 4. The relative risk does not increase by prolonged ingestion of estrogen preparations in general and not for conjugated estrogens especially. 5. In the presence of other risk factors such as nulligravity, hypertension, obesity the relative risk for the development of carcinoma of the endometrium is significantly decreased when estrogens were taken, especially when the coincidental risk factor to estrogen ingestion was obesity. The above results suggest that the restraint in the prescription of estrogen for fear of endometrial carcinoma is not justified.", "contents": "[Estrogen therapy and carcinoma of the endometrium (author's transl)]. The public discussion and the discussion among gynaecologists about the possible increased risk to develop carcinoma of the endometrium following post menopausal treatment with estrogens has lead to insecurity and restricted attitudes in the prescriptions of estrogens. In a statistic comparison of matched pairs of 130 cases of carcinoma of the endometrium with an equal number of selected control cases the following findings were elucidated: 1. Any estrogen preparations do not increase the relative risk for the development of carcinoma of the endometrium. 2. Differentiation into conjugated estrogens, estriol, oral contraceptives and various other estrogen compounds showed a similar trend. 3. Estrogen-androgen compounds and estrodiol compounds did not increase the relative risk for endometrial carcinoma. 4. The relative risk does not increase by prolonged ingestion of estrogen preparations in general and not for conjugated estrogens especially. 5. In the presence of other risk factors such as nulligravity, hypertension, obesity the relative risk for the development of carcinoma of the endometrium is significantly decreased when estrogens were taken, especially when the coincidental risk factor to estrogen ingestion was obesity. The above results suggest that the restraint in the prescription of estrogen for fear of endometrial carcinoma is not justified."}
{"id": "PMID:210089", "title": "Prolyl hydroxylase activity in serum and rectal mucosa in inflammatory bowel disease.", "content": "Prolyl hydroxylase activity in rectal mucosa was found to be significantly greater in 11 patients with Crohn's disease than in 11 control subjects with the irritable bowel syndrome and 16 patients with ulcerative colitis (P less than 0.005). Seven of the patients with Crohn's disease had a histologically normal rectum. This abnormality in apparently normal mucosa supports the concept that Crohn's disease is a 'continuous' disease of the gastrointestinal tract. Although there was no significant difference in prolyl hydroxylase activity between control subjects and patients with ulcerative colitis, those patients with quiescent disease tended to have lower values than those with active mucosal inflammation. Prolyl hydroxylase activity could not, however, be detected in the sera of either healthy control subjects or patients with inflammatory bowel disease.", "contents": "Prolyl hydroxylase activity in serum and rectal mucosa in inflammatory bowel disease. Prolyl hydroxylase activity in rectal mucosa was found to be significantly greater in 11 patients with Crohn's disease than in 11 control subjects with the irritable bowel syndrome and 16 patients with ulcerative colitis (P less than 0.005). Seven of the patients with Crohn's disease had a histologically normal rectum. This abnormality in apparently normal mucosa supports the concept that Crohn's disease is a 'continuous' disease of the gastrointestinal tract. Although there was no significant difference in prolyl hydroxylase activity between control subjects and patients with ulcerative colitis, those patients with quiescent disease tended to have lower values than those with active mucosal inflammation. Prolyl hydroxylase activity could not, however, be detected in the sera of either healthy control subjects or patients with inflammatory bowel disease."}
{"id": "PMID:210091", "title": "[Encephalotomography and computer tomography for abnormalities of the sella (author's transl)].", "content": "Seventy-four patients with tumors in the sellar region were examined by means of encephalotomography and axial computerised tomography. In nearly all cases, the localisation and expansion of tumors could be exactly determined by encephalotomography. In addition, a graduation according to the degree of hypothalamic compression was possible. In cases of density differences between tumor and brain tissue and contrast enhancement more information of the inner structure of a tumor (cystic or solid) could be obtained by computerised tomography. But in cases of missing density differences or/and contrast enhancement tumor diagnosis is easier by encephalotomography because of the high efficiency of encephalotomography. The indication for the form of operative treatment, transsphenoidal or transcranial, depends on the exact knowledge of tumor growth, especially of the degree of hypothalamic compression. Therefore, in all uncertain computerised diagnosis encephalotomography has to be undertained.", "contents": "[Encephalotomography and computer tomography for abnormalities of the sella (author's transl)]. Seventy-four patients with tumors in the sellar region were examined by means of encephalotomography and axial computerised tomography. In nearly all cases, the localisation and expansion of tumors could be exactly determined by encephalotomography. In addition, a graduation according to the degree of hypothalamic compression was possible. In cases of density differences between tumor and brain tissue and contrast enhancement more information of the inner structure of a tumor (cystic or solid) could be obtained by computerised tomography. But in cases of missing density differences or/and contrast enhancement tumor diagnosis is easier by encephalotomography because of the high efficiency of encephalotomography. The indication for the form of operative treatment, transsphenoidal or transcranial, depends on the exact knowledge of tumor growth, especially of the degree of hypothalamic compression. Therefore, in all uncertain computerised diagnosis encephalotomography has to be undertained."}
{"id": "PMID:210092", "title": "[Internal carotid artery supply of juvenile angiofibromas (author's transl)].", "content": "Twelve juvenile angiofibromas of the paranasal sinuses are described which were partly supplied by branches of the internal carotid artery. Five vessels were found to be involved; with increasing frequency they were: the middle cerebral artery, the dorsal meningeal artery, the ethmoidal arteries, the artery of the inferior cavernous sinus and the artery of the pterigoid canal. Intracranial extension of tumour occurred only once, but the paranasal sinuses were involved in all cases. Occasionally, early filling of veins was seen. The branches of the internal carotid artery played a small part in the arterial supply when compared with branches of the external carotid artery. In spite of this, up to 80% of the tumour could be opacified through internal branches. Bilateral internal artery supply stresses the necessity for selective demonstration of both internal and both external carotid arteries.", "contents": "[Internal carotid artery supply of juvenile angiofibromas (author's transl)]. Twelve juvenile angiofibromas of the paranasal sinuses are described which were partly supplied by branches of the internal carotid artery. Five vessels were found to be involved; with increasing frequency they were: the middle cerebral artery, the dorsal meningeal artery, the ethmoidal arteries, the artery of the inferior cavernous sinus and the artery of the pterigoid canal. Intracranial extension of tumour occurred only once, but the paranasal sinuses were involved in all cases. Occasionally, early filling of veins was seen. The branches of the internal carotid artery played a small part in the arterial supply when compared with branches of the external carotid artery. In spite of this, up to 80% of the tumour could be opacified through internal branches. Bilateral internal artery supply stresses the necessity for selective demonstration of both internal and both external carotid arteries."}
{"id": "PMID:210094", "title": "Studies on the pituitary \"Fettstoffwechselhormon\". VIII. Radioimmunoassay of the lipolytic factor P-LF II D.", "content": "A radioimmunoassay of the lipolytic peptide P-LF II D from porcine pituitaries is described. The assay is performed with 125-iodine labeled P-LF II D and with antisera either from guinea pigs or from rabbits. Bound antigen is separated from the free by double antibody technique. No cross reaction is observed with gamma lipotropin, peptide B, secretin, glucagon, isoproterenol. Due to contamination P-LF II C, beta lipotropin and human growth hormone displace the tracer when added at large doses. Complete cross reaction is observed between porcine 1-39 ACTH and P-LF II D. Specificity of this reaction is demonstrated by the increase of cross reaction, when ACTH fragments of increasing length of the polypeptide chain are used (1-23 ACTH, 1-24 ACTH and 1-28 ACTH).", "contents": "Studies on the pituitary \"Fettstoffwechselhormon\". VIII. Radioimmunoassay of the lipolytic factor P-LF II D. A radioimmunoassay of the lipolytic peptide P-LF II D from porcine pituitaries is described. The assay is performed with 125-iodine labeled P-LF II D and with antisera either from guinea pigs or from rabbits. Bound antigen is separated from the free by double antibody technique. No cross reaction is observed with gamma lipotropin, peptide B, secretin, glucagon, isoproterenol. Due to contamination P-LF II C, beta lipotropin and human growth hormone displace the tracer when added at large doses. Complete cross reaction is observed between porcine 1-39 ACTH and P-LF II D. Specificity of this reaction is demonstrated by the increase of cross reaction, when ACTH fragments of increasing length of the polypeptide chain are used (1-23 ACTH, 1-24 ACTH and 1-28 ACTH)."}
{"id": "PMID:210095", "title": "Urinary cyclic AMP in hyperthyroidism.", "content": "Urinary cyclic AMP was studied in 22 female and in 6 male hyperthyroid normocalcemic patients and in 3 hyperthyroid hypercalcemic men. Cyclic AMP/creatinine ratios were elevated both in female (4.12 +/- 0.26 mumoles/gm creatinine) and male (3.92 +/- 0.41 mumoles/gm creatinine) hyperthyroid normocalcemic patients as compared with normal female and male controls (2.85 +/- 0.20 and 2.54 +/- 0.14 mumoles/gm creatinine, respectively). However, there was no difference in the 24-hour urinary cyclic AMP excretion of both hyperthyroid and normal subjects. The hyperthyroid hypercalcemic men excreted less (2.47 +/- 0.19) mumoles/24 hr) cyclic AMP/24 hr than the normal male controls. In the thirteen female patients, studied when euthyroid, the cyclic AMP/creatinine ratio was normalised.", "contents": "Urinary cyclic AMP in hyperthyroidism. Urinary cyclic AMP was studied in 22 female and in 6 male hyperthyroid normocalcemic patients and in 3 hyperthyroid hypercalcemic men. Cyclic AMP/creatinine ratios were elevated both in female (4.12 +/- 0.26 mumoles/gm creatinine) and male (3.92 +/- 0.41 mumoles/gm creatinine) hyperthyroid normocalcemic patients as compared with normal female and male controls (2.85 +/- 0.20 and 2.54 +/- 0.14 mumoles/gm creatinine, respectively). However, there was no difference in the 24-hour urinary cyclic AMP excretion of both hyperthyroid and normal subjects. The hyperthyroid hypercalcemic men excreted less (2.47 +/- 0.19) mumoles/24 hr) cyclic AMP/24 hr than the normal male controls. In the thirteen female patients, studied when euthyroid, the cyclic AMP/creatinine ratio was normalised."}
{"id": "PMID:210096", "title": "Cyclic AMP mediated increased amino acid transport: effect of isoproterenol administration.", "content": "A single injection of isoproterenol (IPR) stimulates cell proliferation in rodent salivary glands after a lag period of about 24 hrs. Among the many events occurring prior to stimulated DNA synthesis, there is an early increase in cAMP levels and elevated transport of amino acids into the parotid gland. Amino acid transport is also elevated in liver and pancreas, tissues not induced to proliferate by IPR. IPR-stimulated alpha-aminoisobutyric acid (AIB) transport in parotid, pancreas and liver is augmented by prior injection of theophylline and is mimicked by dibutyryl cAMP. In all three tissues, changes in cAMP levels and subsequent increases in AIB transport appear to be closely related events. Since only the parotid gland is stimulated to grow after IPR injection, amino acid transport and growth would not appear to be directly related.", "contents": "Cyclic AMP mediated increased amino acid transport: effect of isoproterenol administration. A single injection of isoproterenol (IPR) stimulates cell proliferation in rodent salivary glands after a lag period of about 24 hrs. Among the many events occurring prior to stimulated DNA synthesis, there is an early increase in cAMP levels and elevated transport of amino acids into the parotid gland. Amino acid transport is also elevated in liver and pancreas, tissues not induced to proliferate by IPR. IPR-stimulated alpha-aminoisobutyric acid (AIB) transport in parotid, pancreas and liver is augmented by prior injection of theophylline and is mimicked by dibutyryl cAMP. In all three tissues, changes in cAMP levels and subsequent increases in AIB transport appear to be closely related events. Since only the parotid gland is stimulated to grow after IPR injection, amino acid transport and growth would not appear to be directly related."}
{"id": "PMID:210098", "title": "Iodide induced suppression of thyrotropin-stimulated adenosine 3',5'-monophosphate production in cat thyroid slices.", "content": "Cat thyroid slices were studied to investigate their responsiveness to thyrotropin stimulation of cyclic AMP accumulation. Ovine and bovine thyrotropin, in the presence of 2.5 mM aminophylline, induced a dose-dependent increase in the cyclic AMP content of cat thyroid tissue. Half-maximal stimulation of cyclic AMP accumulation was obtained at a thyrotropin concentration of 1-2 mU/ml. The maximal effect of thyrotropin was observed at 10 mU/ml, and was associated with a mean 77 +/- 19-fold increase in thyroidal cyclic AMP. Preincubation of cat thyroid tissue for 2 h with 50 micron NaI resulted in an impairment in the subsequent ability of thyrotropin to enhance cyclic AMP accumulation, without altering the level of cyclic AMP in tissues not exposed to the hormone. Preincubation alone was without effect on thyrotropin stimulation of cyclic AMP, and the inhibitory effect of iodide was prevented by addition of 3 mM methimazole to the preincubation medium. In addition, the time course of thytrotropin stimulation of cyclic AMP accumulation in cat thyroid slices was not significantly altered by the preincubation with excess iodide. These studies provide additional evidence that excess iodide inhibits the adenylate cyclase-cyclic AMP system in thyroid tissue.", "contents": "Iodide induced suppression of thyrotropin-stimulated adenosine 3',5'-monophosphate production in cat thyroid slices. Cat thyroid slices were studied to investigate their responsiveness to thyrotropin stimulation of cyclic AMP accumulation. Ovine and bovine thyrotropin, in the presence of 2.5 mM aminophylline, induced a dose-dependent increase in the cyclic AMP content of cat thyroid tissue. Half-maximal stimulation of cyclic AMP accumulation was obtained at a thyrotropin concentration of 1-2 mU/ml. The maximal effect of thyrotropin was observed at 10 mU/ml, and was associated with a mean 77 +/- 19-fold increase in thyroidal cyclic AMP. Preincubation of cat thyroid tissue for 2 h with 50 micron NaI resulted in an impairment in the subsequent ability of thyrotropin to enhance cyclic AMP accumulation, without altering the level of cyclic AMP in tissues not exposed to the hormone. Preincubation alone was without effect on thyrotropin stimulation of cyclic AMP, and the inhibitory effect of iodide was prevented by addition of 3 mM methimazole to the preincubation medium. In addition, the time course of thytrotropin stimulation of cyclic AMP accumulation in cat thyroid slices was not significantly altered by the preincubation with excess iodide. These studies provide additional evidence that excess iodide inhibits the adenylate cyclase-cyclic AMP system in thyroid tissue."}
{"id": "PMID:210101", "title": "Monophasic synovial sarcoma--a histological entity?", "content": "Consideration is given to the concept of a histologically identifiable monophasic type of synovial sarcoma. It is accepted that a sarcomatous tumour may be encountered where the spindle cells assume a somewhat epithelioid appearance associated with a reticulin pattern unlike that of most other spindle cell sarcomas. The appearance should alert a hsitopathologist to the possibility of a synovial sarcoma and prompt the examination of multiple additional sections in an attempt to find the pathognomonic biphasic pattern. It is not, however, believed that an entire tumour composed of cells of a single type could be identified with certainty as a synovial sarcoma by light microscopy. The term monophasic synovial sarcoma is worthy of retention, but only as a guide towards the establishment of a definite diagnosis by further sampling of the specimen. Other features suggestive of this diagnosis are discussed.", "contents": "Monophasic synovial sarcoma--a histological entity? Consideration is given to the concept of a histologically identifiable monophasic type of synovial sarcoma. It is accepted that a sarcomatous tumour may be encountered where the spindle cells assume a somewhat epithelioid appearance associated with a reticulin pattern unlike that of most other spindle cell sarcomas. The appearance should alert a hsitopathologist to the possibility of a synovial sarcoma and prompt the examination of multiple additional sections in an attempt to find the pathognomonic biphasic pattern. It is not, however, believed that an entire tumour composed of cells of a single type could be identified with certainty as a synovial sarcoma by light microscopy. The term monophasic synovial sarcoma is worthy of retention, but only as a guide towards the establishment of a definite diagnosis by further sampling of the specimen. Other features suggestive of this diagnosis are discussed."}
{"id": "PMID:210102", "title": "Primary carcinoma of the trachea.", "content": "Two cases of primary carcinoma of the trachea are described. Both patients were female and had smoked cigarettes for many years. One of the tumours was a squamous cell carcinoma and the other an oat cell carcinoma, the commonest and the rarest forms of tracheal cancer respectively. The diagnosis in the case of oat cell carcinoma was confirmed by electron-microscopic demonstration of neurosecretory granules, a unique observation at this site. Oat cell carcinoma of the trachea does not appear to have been recorded previously in a female.", "contents": "Primary carcinoma of the trachea. Two cases of primary carcinoma of the trachea are described. Both patients were female and had smoked cigarettes for many years. One of the tumours was a squamous cell carcinoma and the other an oat cell carcinoma, the commonest and the rarest forms of tracheal cancer respectively. The diagnosis in the case of oat cell carcinoma was confirmed by electron-microscopic demonstration of neurosecretory granules, a unique observation at this site. Oat cell carcinoma of the trachea does not appear to have been recorded previously in a female."}
{"id": "PMID:210103", "title": "The liver in coeliac disease.", "content": "The pathology of the liver in 19 cases of malabsorption is reported. Five of these were proven to have adult coeliac disease, in the others that diagnosis was presumed by exclusion of other causes of malabsorption and by the coincidence of other conditions known to be associated with coeliac disease. Of these cases, three had liver changes of chronic hepatitis and two of these were in the proven coeliac group, including a case with cirrhosis and a hepatoma. In addition, less severe liver changes such as portal tract fibrosis and portal tract infiltration by inflammatory cells were present greatly in excess to that of the controls. The reasons for the occurrence of liver damage in coeliac disease are outlined and discussed in relation to the liver disorders associated with jejunoileal bypass used in the treatment of obesity. Possible mechanisms of liver injury in coeliac disease are described.", "contents": "The liver in coeliac disease. The pathology of the liver in 19 cases of malabsorption is reported. Five of these were proven to have adult coeliac disease, in the others that diagnosis was presumed by exclusion of other causes of malabsorption and by the coincidence of other conditions known to be associated with coeliac disease. Of these cases, three had liver changes of chronic hepatitis and two of these were in the proven coeliac group, including a case with cirrhosis and a hepatoma. In addition, less severe liver changes such as portal tract fibrosis and portal tract infiltration by inflammatory cells were present greatly in excess to that of the controls. The reasons for the occurrence of liver damage in coeliac disease are outlined and discussed in relation to the liver disorders associated with jejunoileal bypass used in the treatment of obesity. Possible mechanisms of liver injury in coeliac disease are described."}
{"id": "PMID:210104", "title": "Histological discrimination of malignancy in mucinous ovarian tumours.", "content": "Eight histological features were measured quantitatively in a group of 77 ovarian mucinous carcinomas and a group of 28 benign mucinous cystomas. These were compared with the duration of survival of the patients and the clinical staging of the tumours. Using the method of discriminant function analysis it was possible to identify a group of tumours of 'borderline malignancy'. Although single histological features were inadequate indicators of prognosis a combination of three features proved fairly accurate.", "contents": "Histological discrimination of malignancy in mucinous ovarian tumours. Eight histological features were measured quantitatively in a group of 77 ovarian mucinous carcinomas and a group of 28 benign mucinous cystomas. These were compared with the duration of survival of the patients and the clinical staging of the tumours. Using the method of discriminant function analysis it was possible to identify a group of tumours of 'borderline malignancy'. Although single histological features were inadequate indicators of prognosis a combination of three features proved fairly accurate."}
{"id": "PMID:210107", "title": "An improved syncytia infectivity assay for the bovine leukemia virus.", "content": "Several factors that influence the sensitivity of the syncytia infectivity assay for the bovine leukemia virus (BLV) and BLV-infected lymphocytes have been examined. The use of early-passage indicator bovine embryonic spleen (BESP) cells and their pretreatment with diethylamino-ethyl-dextran (DEAE-D) was essential for optimal sensitivity. Polybrene was less effective than DEAE-D. The combination of DEAE-D and polybrene was more effective than DEAE-D alone when BLV-infected leukocytes were used as the inoculum, but not when the inoculum was a cell-free BLV preparation. Using BESP cell passages 4 to 11 as indicators, reproducible titers were obtained when aliquots of the same virus stock were assayed at different times after freezer storage. When assaying peripheral blood lymphocytes from infected cattle, optimal syncytia responses were observed consistently by inoculating 5 X 10(6) viable lymphocytes per 60-mm Falcon dish. Centrifugation of peripheral blood leukocytes from BLV-infected cattle in discontinuous bovine serum albumin gradients can be used to separate a subpopulation of infected lymphocytes. Use of this subpopulation as the inoculum, rather than unseparated buffy-coat leukocytes, greatly increases the sensitivity of the syncytia infectivity assay.", "contents": "An improved syncytia infectivity assay for the bovine leukemia virus. Several factors that influence the sensitivity of the syncytia infectivity assay for the bovine leukemia virus (BLV) and BLV-infected lymphocytes have been examined. The use of early-passage indicator bovine embryonic spleen (BESP) cells and their pretreatment with diethylamino-ethyl-dextran (DEAE-D) was essential for optimal sensitivity. Polybrene was less effective than DEAE-D. The combination of DEAE-D and polybrene was more effective than DEAE-D alone when BLV-infected leukocytes were used as the inoculum, but not when the inoculum was a cell-free BLV preparation. Using BESP cell passages 4 to 11 as indicators, reproducible titers were obtained when aliquots of the same virus stock were assayed at different times after freezer storage. When assaying peripheral blood lymphocytes from infected cattle, optimal syncytia responses were observed consistently by inoculating 5 X 10(6) viable lymphocytes per 60-mm Falcon dish. Centrifugation of peripheral blood leukocytes from BLV-infected cattle in discontinuous bovine serum albumin gradients can be used to separate a subpopulation of infected lymphocytes. Use of this subpopulation as the inoculum, rather than unseparated buffy-coat leukocytes, greatly increases the sensitivity of the syncytia infectivity assay."}
{"id": "PMID:210108", "title": "The reduced extracellular calcium requirement for proliferation by neoplastic hepatocytes.", "content": "Cells from neonatal rat livers were unable to maintain DNA-synthetic activity in calcium-deficient medium, but neoplastic hepatocytes from Morris hepatomas 5123 tc and 7795 synthesized DNA and proliferated indefinitely in this calcium-deficient medium. The calcium content of fresh hepatoma tissue from which these cultures were derived was as much as 10 times greater than that of normal liver; but this difference could not account for the insensitivity of neoplastic cells to extracellular calcium because it disappeared during subsequent cultivation in vitro.", "contents": "The reduced extracellular calcium requirement for proliferation by neoplastic hepatocytes. Cells from neonatal rat livers were unable to maintain DNA-synthetic activity in calcium-deficient medium, but neoplastic hepatocytes from Morris hepatomas 5123 tc and 7795 synthesized DNA and proliferated indefinitely in this calcium-deficient medium. The calcium content of fresh hepatoma tissue from which these cultures were derived was as much as 10 times greater than that of normal liver; but this difference could not account for the insensitivity of neoplastic cells to extracellular calcium because it disappeared during subsequent cultivation in vitro."}
{"id": "PMID:210126", "title": "On the relationship between inflammation and altered cAMP metabolism in lungs of B pertussis-vaccinated mice.", "content": "Bordetella pertussis-vaccinated mice were examined for evidence of inflammation. Using polymorphonuclear leukocyte and fluid accumulation as markers, inflammation was evidenced in the lungs and to a lesser extent in the livers of such mice. Both heart and kidney showed no evidence of inflammation. Development of the inflammatory lesion followed a time course similar to that previously reported for increased sensitivity to histamine-mediated cAMP accumulation. This close parrallelism between inflammation and altered cAMP metabolism supports the hypothesis that the increased  cAMP accumulation might be related to a feedback mechanism regulating inflammatory mediator release.", "contents": "On the relationship between inflammation and altered cAMP metabolism in lungs of B pertussis-vaccinated mice. Bordetella pertussis-vaccinated mice were examined for evidence of inflammation. Using polymorphonuclear leukocyte and fluid accumulation as markers, inflammation was evidenced in the lungs and to a lesser extent in the livers of such mice. Both heart and kidney showed no evidence of inflammation. Development of the inflammatory lesion followed a time course similar to that previously reported for increased sensitivity to histamine-mediated cAMP accumulation. This close parrallelism between inflammation and altered cAMP metabolism supports the hypothesis that the increased  cAMP accumulation might be related to a feedback mechanism regulating inflammatory mediator release."}
{"id": "PMID:210127", "title": "Animal studies on the efficacy of an inactivated herpes simplex virus vaccine against recurrent herpes infection.", "content": "The efficacy of inactivated herpes simplex virus vaccines for the treatment of recurrent herpes infection was studied in an animal model. Neither the frequency nor the severity of recurrent herpetic lesions could be influenced by long-term treatment of the animals with these vaccines.", "contents": "Animal studies on the efficacy of an inactivated herpes simplex virus vaccine against recurrent herpes infection. The efficacy of inactivated herpes simplex virus vaccines for the treatment of recurrent herpes infection was studied in an animal model. Neither the frequency nor the severity of recurrent herpetic lesions could be influenced by long-term treatment of the animals with these vaccines."}
{"id": "PMID:210128", "title": "Conditions required for induction of murine p30 by herpes simplex virus.", "content": "Mouse cells (line N cIA cl10) contain 1.2-2.5 ng murine leukaemia virus (MuLV) p30 antigen/mg of protein; this amount of antigen is measurable by competition radioimmunoassay (RIA) but is not detectable by indirect immunofluorescence (IF). Infection of N cIA cl10 cells with herpes simplex virus type 2 (HSV-2) induces expression of MuLV p30. Induction by HSV-2 does not require either cell or virus DNA synthesis and is optimal 8 h post infection when cells at 50-70% confluence are infected at a multiplicity of infection (MOI) of 5-8 PFU/cell. At an MOI of 2.5, 70-80% of the cells express HSV antigens while none of the cells express p30; at an MOI of 5.0, 70-80% of the cells express HSV antigens but 55% of the cells express p30. Using the conditions reported in this paper for preparation of competing antigen, induction of p30 by HSV-2 (strain 333) infection is not measurable by competition RIA.", "contents": "Conditions required for induction of murine p30 by herpes simplex virus. Mouse cells (line N cIA cl10) contain 1.2-2.5 ng murine leukaemia virus (MuLV) p30 antigen/mg of protein; this amount of antigen is measurable by competition radioimmunoassay (RIA) but is not detectable by indirect immunofluorescence (IF). Infection of N cIA cl10 cells with herpes simplex virus type 2 (HSV-2) induces expression of MuLV p30. Induction by HSV-2 does not require either cell or virus DNA synthesis and is optimal 8 h post infection when cells at 50-70% confluence are infected at a multiplicity of infection (MOI) of 5-8 PFU/cell. At an MOI of 2.5, 70-80% of the cells express HSV antigens while none of the cells express p30; at an MOI of 5.0, 70-80% of the cells express HSV antigens but 55% of the cells express p30. Using the conditions reported in this paper for preparation of competing antigen, induction of p30 by HSV-2 (strain 333) infection is not measurable by competition RIA."}
{"id": "PMID:210130", "title": "A portion of the feline leukaemia virus genome is not endogenous in cat cells.", "content": "Although viral sequences closely related to feline leukaemia virus are represented in multiple copies in cellular DNA of all domestic cats, a specific fraction was present only in the virus-infected cells. This fraction was detected by viral cDNA enriched by a prior absorption of a total complementary DNA (cDNA) transcript with normal cat liver DNA. The recycled cDNA hybridized well with the cellular DNA of virus-infected cells, but to a lesser extent with DNA from uninfected cat cells. The probe was used to differentiate virus-positive from virus-negative tumour tissues of cats. The same approach with cDNA of another endogenous feline virus, RD114, failed to show any difference between a virus-infected cell line and normal cells, including both virus-inducible and non-inducible lines.", "contents": "A portion of the feline leukaemia virus genome is not endogenous in cat cells. Although viral sequences closely related to feline leukaemia virus are represented in multiple copies in cellular DNA of all domestic cats, a specific fraction was present only in the virus-infected cells. This fraction was detected by viral cDNA enriched by a prior absorption of a total complementary DNA (cDNA) transcript with normal cat liver DNA. The recycled cDNA hybridized well with the cellular DNA of virus-infected cells, but to a lesser extent with DNA from uninfected cat cells. The probe was used to differentiate virus-positive from virus-negative tumour tissues of cats. The same approach with cDNA of another endogenous feline virus, RD114, failed to show any difference between a virus-infected cell line and normal cells, including both virus-inducible and non-inducible lines."}
{"id": "PMID:210133", "title": "Enzymatic digestion of DNA gamma-irradiated in aqueous solution separation of the digests by ion-exchange chromatography.", "content": "Aqueous solutions of DNA were gamma-irradiated in the presence and absence of oxygen and enzymatically hydrolysed by the combined action of pancreatic deoxyribonuclease (DNase I), snake-venom phosphodiesterase (PDE I), spleen phosphodiesterase (PDE II) and alkaline phosphatase. In contrast to unirradiated DNA, which is fully hydrolysed to nucleosides by these enzymes, gamma-irradiated DNA yields a series of oligonucleotides. Their isolation might enalbe the future identification of the chemical nature of DNA lesions.", "contents": "Enzymatic digestion of DNA gamma-irradiated in aqueous solution separation of the digests by ion-exchange chromatography. Aqueous solutions of DNA were gamma-irradiated in the presence and absence of oxygen and enzymatically hydrolysed by the combined action of pancreatic deoxyribonuclease (DNase I), snake-venom phosphodiesterase (PDE I), spleen phosphodiesterase (PDE II) and alkaline phosphatase. In contrast to unirradiated DNA, which is fully hydrolysed to nucleosides by these enzymes, gamma-irradiated DNA yields a series of oligonucleotides. Their isolation might enalbe the future identification of the chemical nature of DNA lesions."}
{"id": "PMID:210134", "title": "Inhibition of x-ray-induced protection of Escherichia coli K-12 cells against the lethal effects of ultra-violet light by nitrofurantoin.", "content": "Wild-type cells of E. coli K-12 showed increasing U.V. resistance if they were X-irradiated and incubated at 37 degrees C in growth medium before the U.V. exposure. Development of higher U.V. resistance could be inhibited by incubating the X-irradiated cells either at temperatures below 15 degrees C, or in the presence of 0.01 M KCN. Nitrofurantoin (NF), which was recently found specifically to inhibit inducible enzyme synthesis, had only a transient inhibitory effect on X-ray-induced U.V. resistance. Cells grown in glucose medium showed less inhibition by NF of X-radiation-induced resistance to U.V.-radiation than did cells grown in glycerol, or in glucose medium with added cyclic AMP. It is suggested that X-ray-induced U.V. resistance requires active cellular metabolism, but it is not subject to catabolite repression. The following hypothesis is offered to explain the action of NF: Under de-repressed conditions (without catabolite repression by glucose) nitrofurantoin could counteract the radiation-induced inhibition of a repair inhibitor (such as post-irradiation DNA degradation).", "contents": "Inhibition of x-ray-induced protection of Escherichia coli K-12 cells against the lethal effects of ultra-violet light by nitrofurantoin. Wild-type cells of E. coli K-12 showed increasing U.V. resistance if they were X-irradiated and incubated at 37 degrees C in growth medium before the U.V. exposure. Development of higher U.V. resistance could be inhibited by incubating the X-irradiated cells either at temperatures below 15 degrees C, or in the presence of 0.01 M KCN. Nitrofurantoin (NF), which was recently found specifically to inhibit inducible enzyme synthesis, had only a transient inhibitory effect on X-ray-induced U.V. resistance. Cells grown in glucose medium showed less inhibition by NF of X-radiation-induced resistance to U.V.-radiation than did cells grown in glycerol, or in glucose medium with added cyclic AMP. It is suggested that X-ray-induced U.V. resistance requires active cellular metabolism, but it is not subject to catabolite repression. The following hypothesis is offered to explain the action of NF: Under de-repressed conditions (without catabolite repression by glucose) nitrofurantoin could counteract the radiation-induced inhibition of a repair inhibitor (such as post-irradiation DNA degradation)."}
{"id": "PMID:210135", "title": "Antigen-inducing ability of herpesvirus papio in human and baboon lymphoma lines, compared to Epstein-Barr virus.", "content": "Herpesvirus papio(HVP)-carrying baboon lymphoblastoid lines do not express a nuclear antigen like the Epstein-Barr virus(EBV)-determined nuclear antigen (EBNA), as judged by in situ anticomplement fluorescence staining, although the carry multiple viral genomes and, in the case of producerlines, early antigen (EA) and viral capsid antigen (VCA) that cross-react with the corresponding human EBV-determined antigens. To test whether the lack of in situ nuclear antigen expression is a property innate to the baboon virus or the baboon cell, nonproducer HVP-carrying baboon lymphoid cells of the 26 CB-1 line were superinfected with two human EBV strains. B95-8-derived EBV induced brilliant EBNA staining, proving that the baboon lymphoid cell was competent to synthesize EBNA. In the mirror experiment, HVP derived from the 9B or the 18C baboon line was added to the EBV-carrying Raji line, the EBV-negative Ramos and BJAB lines and the HVP-carrying nonproducer 26 CB-1 line, respectively. HVP induced EA and VCA in Raji, and EA in BJAB and 26 CB-1. EBNA was not induced in any of the three EBNA-negative lines, BJAB, Ramos and 26 CB-1. It is concluded that the lack of in situ nuclear staining in HVP-carrying baboon lines is a HVP-associated property and is not due to any innate inability of the baboon lymphoid cell to synthesize an antigen of the EBNA type.", "contents": "Antigen-inducing ability of herpesvirus papio in human and baboon lymphoma lines, compared to Epstein-Barr virus. Herpesvirus papio(HVP)-carrying baboon lymphoblastoid lines do not express a nuclear antigen like the Epstein-Barr virus(EBV)-determined nuclear antigen (EBNA), as judged by in situ anticomplement fluorescence staining, although the carry multiple viral genomes and, in the case of producerlines, early antigen (EA) and viral capsid antigen (VCA) that cross-react with the corresponding human EBV-determined antigens. To test whether the lack of in situ nuclear antigen expression is a property innate to the baboon virus or the baboon cell, nonproducer HVP-carrying baboon lymphoid cells of the 26 CB-1 line were superinfected with two human EBV strains. B95-8-derived EBV induced brilliant EBNA staining, proving that the baboon lymphoid cell was competent to synthesize EBNA. In the mirror experiment, HVP derived from the 9B or the 18C baboon line was added to the EBV-carrying Raji line, the EBV-negative Ramos and BJAB lines and the HVP-carrying nonproducer 26 CB-1 line, respectively. HVP induced EA and VCA in Raji, and EA in BJAB and 26 CB-1. EBNA was not induced in any of the three EBNA-negative lines, BJAB, Ramos and 26 CB-1. It is concluded that the lack of in situ nuclear staining in HVP-carrying baboon lines is a HVP-associated property and is not due to any innate inability of the baboon lymphoid cell to synthesize an antigen of the EBNA type."}
{"id": "PMID:210137", "title": "Temperature-sensitive mutants of simian virus 40. I. Isolation aand preliminary characterization of B/C gene mutants.", "content": "Sixteen temperature-sensitive mutants of simian virus 40 were isolated after treatment of wild-type virus with UV light, nitrous acid, or nitrosoguanidine. All of the mutants were assigned to the B complementation group on the basis of quantitative complementation analyses. Characterization of several representative mutants revealed that under restrictive conditions such mutants produced immunologically identifiable tumor and viral capsid antigens, induced the synthesis of cellular DNA, and replicated infectious viral DNA. In addition, mutant particles produced at 33 degrees were more heat-labile than wild-type virus. This collection of mutants will be useful in an analysis of SV40 particle morphogenesis.", "contents": "Temperature-sensitive mutants of simian virus 40. I. Isolation aand preliminary characterization of B/C gene mutants. Sixteen temperature-sensitive mutants of simian virus 40 were isolated after treatment of wild-type virus with UV light, nitrous acid, or nitrosoguanidine. All of the mutants were assigned to the B complementation group on the basis of quantitative complementation analyses. Characterization of several representative mutants revealed that under restrictive conditions such mutants produced immunologically identifiable tumor and viral capsid antigens, induced the synthesis of cellular DNA, and replicated infectious viral DNA. In addition, mutant particles produced at 33 degrees were more heat-labile than wild-type virus. This collection of mutants will be useful in an analysis of SV40 particle morphogenesis."}
{"id": "PMID:210138", "title": "Differential inhibition of host cell RNA synthesis in several picornavirus-infected cell lines.", "content": "Patterns of cellular RNA synthesis during poliovirus (types 1,2 and 3) and mengovirus infections in HeLa, HEp-2, Vero and L-cells were investigated by means of high-resolution autoradiography, kinetics of 3H-uridine incorporation, and sucrose gradient centrifugation. Only mengovirus-infected L-cells showed an early and exponential inhibition of hnRNA and rRNA synthesis. The other cell lines tested, whether infected with polio- or mengovirus, exhibited a slowly and linearly decreasing cellular RNA synthesis, with hnRNA production suppressed completely, although somewhat later than in L-cells, and rRNA synthesis continuing at a gradually reduced rate during the entire viral growth cycle. Locations of cleavage steps of rRNA precursor molecules are discussed.", "contents": "Differential inhibition of host cell RNA synthesis in several picornavirus-infected cell lines. Patterns of cellular RNA synthesis during poliovirus (types 1,2 and 3) and mengovirus infections in HeLa, HEp-2, Vero and L-cells were investigated by means of high-resolution autoradiography, kinetics of 3H-uridine incorporation, and sucrose gradient centrifugation. Only mengovirus-infected L-cells showed an early and exponential inhibition of hnRNA and rRNA synthesis. The other cell lines tested, whether infected with polio- or mengovirus, exhibited a slowly and linearly decreasing cellular RNA synthesis, with hnRNA production suppressed completely, although somewhat later than in L-cells, and rRNA synthesis continuing at a gradually reduced rate during the entire viral growth cycle. Locations of cleavage steps of rRNA precursor molecules are discussed."}
{"id": "PMID:210139", "title": "Synthesis and packaging of herpes simplex virus DNA in the course of virus passages at high multiplicity.", "content": "Herpes simplex virus type 1 (HSV-1), strain ANG, was passaged serially at high MOI or undiluted on RC-37 cells. The yields of infectious virus decreased and increased periodically with a maximum of about 3 log units variation in titer. The amount of newly synthesized HSV-1 DNA, however, did not vary by more than a factor of 2. On the other hand, the fraction of total HSV-1 DNA associated with virions was reduced at passage numbers coinciding with the minima in the yields of infectious progeny virus. Apparently, low yields of infectious virus mainly reflected a reduced efficiency of packaging of viral DNA into mature virus particles. One step in the process of virus maturation which appeared to be impaired was the assembly of nucleocapsids. HSV-1 ang was shown to be capable of generating different classes of defective particle in independent series of virus passages at high MOI.", "contents": "Synthesis and packaging of herpes simplex virus DNA in the course of virus passages at high multiplicity. Herpes simplex virus type 1 (HSV-1), strain ANG, was passaged serially at high MOI or undiluted on RC-37 cells. The yields of infectious virus decreased and increased periodically with a maximum of about 3 log units variation in titer. The amount of newly synthesized HSV-1 DNA, however, did not vary by more than a factor of 2. On the other hand, the fraction of total HSV-1 DNA associated with virions was reduced at passage numbers coinciding with the minima in the yields of infectious progeny virus. Apparently, low yields of infectious virus mainly reflected a reduced efficiency of packaging of viral DNA into mature virus particles. One step in the process of virus maturation which appeared to be impaired was the assembly of nucleocapsids. HSV-1 ang was shown to be capable of generating different classes of defective particle in independent series of virus passages at high MOI."}
{"id": "PMID:210140", "title": "Effect of caffeine on the replication of nonirradiated and ultraviolet-irradiated cytomegalovirus.", "content": "The effect of caffeine on cytomegalovirus (CMV) replication in human embryo lung (HEL) and human embryo kidney (HEK) cells was studied. In HEL cultures, nonirradiated CMV yielded up to 6.7 times more plaques in caffeine-treated cultures than in control cultures. Virus growth curves exhibited different profiles, depending on the time of treatment of the cultures with the drug. Incorporation of [3H]TdR into virus DNA was enhanced and began about 24 h earlier in the caffeine-treated cultures than in the untreated cultures. A relationship between decreased incorporation of [3D]TdR into cellular DNA caused by caffeine and increased virus replication was observed in the HEL cells. In caffeine-treated HEK cultures, CMV replicated better than in untreated cultures in which virus growth was transitory and decreased after 10 days of incubation. The infectivity of CMV irradiated with UV light doses of 3,120-12,480 erg/mm2 decreased as a function of the UV dose. The extent of multiplicity reactivation of the irradiated virus increased when irradiated with higher UV doses. The effect of caffeine on the infectivity of UV-irradiated CMV depended on the dose with which the virus was irradiated. Caffeine increased the infectivity of CMV irradiated with lowest UV dose (3,120 erg/mm2) but did not increase the infectivity of virus irradiated with 12,480 erg/mm2. Multiplicity reactivation of the UV-irradiated CMV was inhibited by caffeine regardless of the UV dose with which the virus was irradiated.", "contents": "Effect of caffeine on the replication of nonirradiated and ultraviolet-irradiated cytomegalovirus. The effect of caffeine on cytomegalovirus (CMV) replication in human embryo lung (HEL) and human embryo kidney (HEK) cells was studied. In HEL cultures, nonirradiated CMV yielded up to 6.7 times more plaques in caffeine-treated cultures than in control cultures. Virus growth curves exhibited different profiles, depending on the time of treatment of the cultures with the drug. Incorporation of [3H]TdR into virus DNA was enhanced and began about 24 h earlier in the caffeine-treated cultures than in the untreated cultures. A relationship between decreased incorporation of [3D]TdR into cellular DNA caused by caffeine and increased virus replication was observed in the HEL cells. In caffeine-treated HEK cultures, CMV replicated better than in untreated cultures in which virus growth was transitory and decreased after 10 days of incubation. The infectivity of CMV irradiated with UV light doses of 3,120-12,480 erg/mm2 decreased as a function of the UV dose. The extent of multiplicity reactivation of the irradiated virus increased when irradiated with higher UV doses. The effect of caffeine on the infectivity of UV-irradiated CMV depended on the dose with which the virus was irradiated. Caffeine increased the infectivity of CMV irradiated with lowest UV dose (3,120 erg/mm2) but did not increase the infectivity of virus irradiated with 12,480 erg/mm2. Multiplicity reactivation of the UV-irradiated CMV was inhibited by caffeine regardless of the UV dose with which the virus was irradiated."}
{"id": "PMID:210141", "title": "Transmission of B77 virus double mutant LA334 markers by transfection.", "content": "Successful transfection of Brown Leghorn chicken fibroblasts was carried out with DNA isolated from duck cells transformed by the LA334 mutant of avian sarcoma virus B77. Transfection of duck cells was negative. The four viruses recovered after transfection were all temperature-sensitive for transformation. Two were fully temperature-sensitive for replication, as shown by analysis of virus replication, by characterization of virus particles produced at the nonpermissive temperature using density gradient centrifugation, and by electron microscopic examination. The other two viruses were only partially temperature-sensitive for replication. The results suggest that both the src and gag regions of the avian sarcoma virus genome are transferred simultaneously during transfection, probably by a single integral provirus copy.", "contents": "Transmission of B77 virus double mutant LA334 markers by transfection. Successful transfection of Brown Leghorn chicken fibroblasts was carried out with DNA isolated from duck cells transformed by the LA334 mutant of avian sarcoma virus B77. Transfection of duck cells was negative. The four viruses recovered after transfection were all temperature-sensitive for transformation. Two were fully temperature-sensitive for replication, as shown by analysis of virus replication, by characterization of virus particles produced at the nonpermissive temperature using density gradient centrifugation, and by electron microscopic examination. The other two viruses were only partially temperature-sensitive for replication. The results suggest that both the src and gag regions of the avian sarcoma virus genome are transferred simultaneously during transfection, probably by a single integral provirus copy."}
{"id": "PMID:210142", "title": "Nuclear accumulation of filamentous herpes simplex virus DNA late during the replicative cycle.", "content": "New ultrastructural findings within the nucleus of herpes simplex virus-infected cells are illustrated. The occurrence of bundles of tightly packed filaments during the late stages of the infectious process is described. These bundles were found in different areas of the nucleus and were not associated with any nuclear organelles. Employing different staining techniques and high-resolution autoradiography, they could be identified as DNA-containing nucleoproteins. These filaments may be interpreted as a special form of viral DNA accumulation within the nucleus. Changes of these structures toward a more recticular arrangement were observed as soon as the nucleoplasm disintegrated.", "contents": "Nuclear accumulation of filamentous herpes simplex virus DNA late during the replicative cycle. New ultrastructural findings within the nucleus of herpes simplex virus-infected cells are illustrated. The occurrence of bundles of tightly packed filaments during the late stages of the infectious process is described. These bundles were found in different areas of the nucleus and were not associated with any nuclear organelles. Employing different staining techniques and high-resolution autoradiography, they could be identified as DNA-containing nucleoproteins. These filaments may be interpreted as a special form of viral DNA accumulation within the nucleus. Changes of these structures toward a more recticular arrangement were observed as soon as the nucleoplasm disintegrated."}
{"id": "PMID:210143", "title": "Purification of hepatitis A virus from human feces.", "content": "Hepatitis A virus was purified fecal specimens obtained from 2 patients with naturally acquired hepatitis A. The purification procedure involved differential centrifugation, organic solvent extraction, agarose gel filtration, ion-exchange chromatography, and isopycnic ultracentrifugation in cesium chloride. Using immune electron microscopy and discontinuous SDS-PAGE, this procedure was found to be effective in removing extraneous material from hepatitis A virus. There was significant recovery of virus as judged by immune electron microscopy and solid-phase radioimmunoassay. Using this protocol, it has been possible to obtain virus preparations of sufficient purity and high enough titer to enable biochemical studies to proceed.", "contents": "Purification of hepatitis A virus from human feces. Hepatitis A virus was purified fecal specimens obtained from 2 patients with naturally acquired hepatitis A. The purification procedure involved differential centrifugation, organic solvent extraction, agarose gel filtration, ion-exchange chromatography, and isopycnic ultracentrifugation in cesium chloride. Using immune electron microscopy and discontinuous SDS-PAGE, this procedure was found to be effective in removing extraneous material from hepatitis A virus. There was significant recovery of virus as judged by immune electron microscopy and solid-phase radioimmunoassay. Using this protocol, it has been possible to obtain virus preparations of sufficient purity and high enough titer to enable biochemical studies to proceed."}
{"id": "PMID:210144", "title": "Herpesvirus morphology: visualization of a structural subunit.", "content": "The presence of spontaneously disrupted cytomegalovirus capsids has made it possible to visualize a subunit within the herpesvirus capsomere. The pattern resolved agreed well with the theoretical net based on the concept of a structural subunit at each apex of the hexon.", "contents": "Herpesvirus morphology: visualization of a structural subunit. The presence of spontaneously disrupted cytomegalovirus capsids has made it possible to visualize a subunit within the herpesvirus capsomere. The pattern resolved agreed well with the theoretical net based on the concept of a structural subunit at each apex of the hexon."}
{"id": "PMID:210147", "title": "Seroepidemiologic aspects of varicella zoster virus infections in an Israeli Jewish population.", "content": "Sera from 872 healthy subjects among the Jewish population of Israel were examined for antibodies to varicella zoster virus (VZV) by a simplified technique for the detection of immunofluorescent antibody to membrane antigen. The difference in the geometric mean titer of antibodies to the virus among the the different age groups was highly significant (P less than 0.0001). The highest titers were found in the five-to-seven-years and 21-to-30-years age groups. In 211 subjects, aged 17 to 40 years, the antibody titres were not influenced by sex or ethnic origin. The percentage of seronegative subjects (titer less than 2) was relatively high--between 18.7 and 32.9% in the 21-to-60-years age groups--and it was 19.5% in the population of childbearing age. The importance of screening for VZV immune status in pregnant women is emphasized.", "contents": "Seroepidemiologic aspects of varicella zoster virus infections in an Israeli Jewish population. Sera from 872 healthy subjects among the Jewish population of Israel were examined for antibodies to varicella zoster virus (VZV) by a simplified technique for the detection of immunofluorescent antibody to membrane antigen. The difference in the geometric mean titer of antibodies to the virus among the the different age groups was highly significant (P less than 0.0001). The highest titers were found in the five-to-seven-years and 21-to-30-years age groups. In 211 subjects, aged 17 to 40 years, the antibody titres were not influenced by sex or ethnic origin. The percentage of seronegative subjects (titer less than 2) was relatively high--between 18.7 and 32.9% in the 21-to-60-years age groups--and it was 19.5% in the population of childbearing age. The importance of screening for VZV immune status in pregnant women is emphasized."}
{"id": "PMID:210148", "title": "Population distribution of histological types of lung cancer: epidemiologic aspects in Israel and review of the literature.", "content": "A nationwide study of lung cancer in Israel during 1968-70 demonstrated a low to moderate incidence in men and a high incidence in women, as compared with other countries. The sex ratio was relatively lower than expected. This discrepancy results from a low rate of squamous cell carcinoma in men and a high rate of adenocarcinoma in women, and is consistent with similar, previously observed trends in North American Jews from New York, Pittsburgh and Montreal. The literature relating to the relative frequencies of various histological subcategories of lung cancer is reviewed and the importance, for etiology and prognosis, of a separate assessment of each distinct cell-type entity is emphasized.", "contents": "Population distribution of histological types of lung cancer: epidemiologic aspects in Israel and review of the literature. A nationwide study of lung cancer in Israel during 1968-70 demonstrated a low to moderate incidence in men and a high incidence in women, as compared with other countries. The sex ratio was relatively lower than expected. This discrepancy results from a low rate of squamous cell carcinoma in men and a high rate of adenocarcinoma in women, and is consistent with similar, previously observed trends in North American Jews from New York, Pittsburgh and Montreal. The literature relating to the relative frequencies of various histological subcategories of lung cancer is reviewed and the importance, for etiology and prognosis, of a separate assessment of each distinct cell-type entity is emphasized."}
{"id": "PMID:210151", "title": "Chemical and electrophoretic changes induced by polymyxin B on outer membrane components from Serratia marcescens.", "content": "The effects of polymyxin B (PB) on outer membrane (OM) components from resistant (strain 08) and sensitive (strain Bizio) cells of Serratia marcescens were characterized by chemical analysis and polyacrylamide gel electrophoresis (PGE) in sodium dodecylsulfate. Chemical analysis revealed no major differences in the OM fractions after PB treatment of both strains, except for the loss of protein in PB treated OM of the sensitive strain. The yield and composition between the lipopolysaccharides (LPS) of the two strains were different both before and after treatment. PGE revealed that there was a complex formation between the LPS of resistant strain and PB but both dissociation and degradation occurred in the LPS components in the sensitive strain. In addition, it was found that the protein components were destabilized by PB with subsequent loss of some of the components from OM of the sensitive strain. The difference in the amount of LPS and their ability to complex with PB may reflect different degrees of antibiotic susceptibility of these two strains of S. marcescens. A sequential multistep mechanism is proposed for the action of PB on outer membranes of this species.", "contents": "Chemical and electrophoretic changes induced by polymyxin B on outer membrane components from Serratia marcescens. The effects of polymyxin B (PB) on outer membrane (OM) components from resistant (strain 08) and sensitive (strain Bizio) cells of Serratia marcescens were characterized by chemical analysis and polyacrylamide gel electrophoresis (PGE) in sodium dodecylsulfate. Chemical analysis revealed no major differences in the OM fractions after PB treatment of both strains, except for the loss of protein in PB treated OM of the sensitive strain. The yield and composition between the lipopolysaccharides (LPS) of the two strains were different both before and after treatment. PGE revealed that there was a complex formation between the LPS of resistant strain and PB but both dissociation and degradation occurred in the LPS components in the sensitive strain. In addition, it was found that the protein components were destabilized by PB with subsequent loss of some of the components from OM of the sensitive strain. The difference in the amount of LPS and their ability to complex with PB may reflect different degrees of antibiotic susceptibility of these two strains of S. marcescens. A sequential multistep mechanism is proposed for the action of PB on outer membranes of this species."}
{"id": "PMID:210152", "title": "Method for maintaining viability of Clostridium perfringens in foods during shipment and storage: collaborative study.", "content": "A collaborative study was conducted in 12 laboratories to determine the effectiveness of a new method for maintaining vegetative cells of Clostridium perfringens in viable condition during storage and transport of food specimens to the laboratory. The collaborative results showed that treatment of brown gravy and roast beef samples with an equal amount by weight of sterile buffered glycerol-sodium chloride solution to give a final 10% glycerol concentration and storage with Dry Ice for 10 days at -56 degrees C resulted in plate counts of C. perfringens which were 2-4 log cycles higher with 2 different strains than counts with untreated specimens stored by the usual method at -20 degrees C. Plate counts obtained with the treated specimens stored with Dry Ice were less than 1 log cycle lower than counts made with identical specimens before freezing for storage and shipment to the collaborators. The results with treated specimens were also more uniform among the different laboratories. Because the new method for storage and shipment of food samples was so effective for maintaining viability of the organism, the official first action method for C. perfringens (46.B01) was changed to incorporate these procedures as part of the method.", "contents": "Method for maintaining viability of Clostridium perfringens in foods during shipment and storage: collaborative study. A collaborative study was conducted in 12 laboratories to determine the effectiveness of a new method for maintaining vegetative cells of Clostridium perfringens in viable condition during storage and transport of food specimens to the laboratory. The collaborative results showed that treatment of brown gravy and roast beef samples with an equal amount by weight of sterile buffered glycerol-sodium chloride solution to give a final 10% glycerol concentration and storage with Dry Ice for 10 days at -56 degrees C resulted in plate counts of C. perfringens which were 2-4 log cycles higher with 2 different strains than counts with untreated specimens stored by the usual method at -20 degrees C. Plate counts obtained with the treated specimens stored with Dry Ice were less than 1 log cycle lower than counts made with identical specimens before freezing for storage and shipment to the collaborators. The results with treated specimens were also more uniform among the different laboratories. Because the new method for storage and shipment of food samples was so effective for maintaining viability of the organism, the official first action method for C. perfringens (46.B01) was changed to incorporate these procedures as part of the method."}
{"id": "PMID:210153", "title": "Galactose catabolism in Caulobacter crescentus.", "content": "Caulobacter crescentus wild-type strain CB13 is unable to utilize galactose as the sole carbon source unless derivatives of cyclic AMP are present. Spontaneous mutants have been isolated which are able to grow on galactose in the absence of exogenous cyclic nucleotides. These mutants and the wild-type strain were used to determine the pathway of galactose catabolism in this organism. It is shown here that C. crescentus catabolizes galactose by the Entner-Duodoroff pathway. Galactose is initially converted to galactonate by galactose dehydrogenase and then 2-keto-3-deoxy-6-phosphogalactonate aldolase catalyzes the hydrolysis of 2-keto-3-deoxy-6-phosphogalactonic acid to yield triose phosphate and pyruvate. Two enzymes of galactose catabolism, galactose dehydrogenase and 2-keto-3-deoxy-6-phosphogalactonate aldolase, were shown to be inducible and independently regulated. Furthermore, galactose uptake was observed to be regulated independently of the galactose catabolic enzymes.", "contents": "Galactose catabolism in Caulobacter crescentus. Caulobacter crescentus wild-type strain CB13 is unable to utilize galactose as the sole carbon source unless derivatives of cyclic AMP are present. Spontaneous mutants have been isolated which are able to grow on galactose in the absence of exogenous cyclic nucleotides. These mutants and the wild-type strain were used to determine the pathway of galactose catabolism in this organism. It is shown here that C. crescentus catabolizes galactose by the Entner-Duodoroff pathway. Galactose is initially converted to galactonate by galactose dehydrogenase and then 2-keto-3-deoxy-6-phosphogalactonate aldolase catalyzes the hydrolysis of 2-keto-3-deoxy-6-phosphogalactonic acid to yield triose phosphate and pyruvate. Two enzymes of galactose catabolism, galactose dehydrogenase and 2-keto-3-deoxy-6-phosphogalactonate aldolase, were shown to be inducible and independently regulated. Furthermore, galactose uptake was observed to be regulated independently of the galactose catabolic enzymes."}
{"id": "PMID:210154", "title": "Induction of collagenase production in Vibrio B-30.", "content": "The inducible nature of an extracellular collagenase produced by a marine Vibrio (Vibrio B-30, ATCC 21250) was demonstrated by observing the increase in extracellular collagenase activity after the addition of collagen to cell cultures in the latter part of the exponential growth phase. When collagenase-hydrolyzed collagen was added, the lag time required before collagenase production was detected decreased significantly compared with cultures receiving collagen. Cells preinduced to synthesize collagenase did not produce the enzyme when collagen was removed from the culture medium. Incorporation of penicillin G had no effect on final collagenase activity levels in suspensions of Vibrio B-30 in complete medium supplemented with collagen. However, chloramphenicol and tetracycline inhibited collagenase production, indicating that de novo protein synthesis was necessary for the appearance of activity. Attempts to isolate the inducing substance(s) involved filtering hydrolyzed collagen through a series of ultrafiltration membranes. The lowest-molecular-weight fraction of collagen hydrolysate with inducing ability was between 1,000 and 10,000. Gel filtration of this fraction on Sephadex G-50 resulted in the appearance of three protein peaks, two of which were capable of inducing collagenase production. Results from amino acid composition and N-terminal amino acid analysis suggest that the inducing substance originates from the polar helical portion of the collagen molecule.", "contents": "Induction of collagenase production in Vibrio B-30. The inducible nature of an extracellular collagenase produced by a marine Vibrio (Vibrio B-30, ATCC 21250) was demonstrated by observing the increase in extracellular collagenase activity after the addition of collagen to cell cultures in the latter part of the exponential growth phase. When collagenase-hydrolyzed collagen was added, the lag time required before collagenase production was detected decreased significantly compared with cultures receiving collagen. Cells preinduced to synthesize collagenase did not produce the enzyme when collagen was removed from the culture medium. Incorporation of penicillin G had no effect on final collagenase activity levels in suspensions of Vibrio B-30 in complete medium supplemented with collagen. However, chloramphenicol and tetracycline inhibited collagenase production, indicating that de novo protein synthesis was necessary for the appearance of activity. Attempts to isolate the inducing substance(s) involved filtering hydrolyzed collagen through a series of ultrafiltration membranes. The lowest-molecular-weight fraction of collagen hydrolysate with inducing ability was between 1,000 and 10,000. Gel filtration of this fraction on Sephadex G-50 resulted in the appearance of three protein peaks, two of which were capable of inducing collagenase production. Results from amino acid composition and N-terminal amino acid analysis suggest that the inducing substance originates from the polar helical portion of the collagen molecule."}
{"id": "PMID:210155", "title": "A mutation altering some properties of the neutral phosphatase in Chlamydomonas reinhardi: possible post-translational modification of phosphatase structure.", "content": "A mutant (PDs-) of Chlamydomonas reinhardi has been isolated which produces an altered neutral phosphatase. The wild-type (PDs+) and mutant (PDs-) phosphatases markedly differed in their thermosensitivities and electrophoretic mobilities. The heterozygous PDs-/PDs+ diploids produced only the wild-type electrophoretic form of the phosphatase. Mixing extracts of PDs- with extracts of various other strains in vitro resulted in the rapid transformation of the PDs- enzymic form into an enzymic variety, the properties (heat sensitivity, electrophoretic mobility) of which were similar to those of the wild-type neutral phosphatase. The results are discussed in relation to the idea that the PDs mutation is located not in the structural gene but rather in a modifying gene acting at the post-translational level.", "contents": "A mutation altering some properties of the neutral phosphatase in Chlamydomonas reinhardi: possible post-translational modification of phosphatase structure. A mutant (PDs-) of Chlamydomonas reinhardi has been isolated which produces an altered neutral phosphatase. The wild-type (PDs+) and mutant (PDs-) phosphatases markedly differed in their thermosensitivities and electrophoretic mobilities. The heterozygous PDs-/PDs+ diploids produced only the wild-type electrophoretic form of the phosphatase. Mixing extracts of PDs- with extracts of various other strains in vitro resulted in the rapid transformation of the PDs- enzymic form into an enzymic variety, the properties (heat sensitivity, electrophoretic mobility) of which were similar to those of the wild-type neutral phosphatase. The results are discussed in relation to the idea that the PDs mutation is located not in the structural gene but rather in a modifying gene acting at the post-translational level."}
{"id": "PMID:210156", "title": "Expression of the histidine operon in rho mutants of Escherichia coli.", "content": "Expression of the Escherichia coli histidine operon was measured in four independently isolated sets of strains carrying ten different rho mutations. Rho factor does not act as a major regulatory element of histidine operon attenuation.", "contents": "Expression of the histidine operon in rho mutants of Escherichia coli. Expression of the Escherichia coli histidine operon was measured in four independently isolated sets of strains carrying ten different rho mutations. Rho factor does not act as a major regulatory element of histidine operon attenuation."}
{"id": "PMID:210157", "title": "Coenzyme B12-dependent diol dehydratase: regulation of apoenzyme synthesis in Klebsiella pneumoniae (Aerobacter aerogenes) ATCC 8724.", "content": "Immunochemical studies demonstrated that Klebsiella pneumoniae (Aerobacter aerogenes) ATCC 8724 produces only a single diol dehydratase whether grown on glycerol or on 1,2-propanediol. The enzyme was subject to induction by 1,2-diols and to catabolite repression reversed by cyclic AMP.", "contents": "Coenzyme B12-dependent diol dehydratase: regulation of apoenzyme synthesis in Klebsiella pneumoniae (Aerobacter aerogenes) ATCC 8724. Immunochemical studies demonstrated that Klebsiella pneumoniae (Aerobacter aerogenes) ATCC 8724 produces only a single diol dehydratase whether grown on glycerol or on 1,2-propanediol. The enzyme was subject to induction by 1,2-diols and to catabolite repression reversed by cyclic AMP."}
{"id": "PMID:210160", "title": "Enzyme-accelerated hydrolysis of polyglycolic acid.", "content": "In a preliminary study of the enzyme-polymer interactions, the role of 15 enzymes in the in vitro hydrolysis of polyglycolic acid has been investigated. Carboxypeptidase A, alpha-chymotrypsin, clostridiopeptidase A and ficin increase the rate of hydrolysis of this synthetic polymer, illustrating the ability of enzymes to influence polymer degradation.", "contents": "Enzyme-accelerated hydrolysis of polyglycolic acid. In a preliminary study of the enzyme-polymer interactions, the role of 15 enzymes in the in vitro hydrolysis of polyglycolic acid has been investigated. Carboxypeptidase A, alpha-chymotrypsin, clostridiopeptidase A and ficin increase the rate of hydrolysis of this synthetic polymer, illustrating the ability of enzymes to influence polymer degradation."}
{"id": "PMID:210161", "title": "The interaction of liver alcohol dehydrogenase with phenyl adenine dinucleotide, a novel analog of pyridine nucleotide coenzymes.", "content": "We have synthesized phenyl adenine dinucleotide (P1-adenosine-5')-P2-(beta-D-ribofuranosylbenzene-5')-pyrophosphate (PhAD), a novel analog of pyridine nucleotide coenzymes. This compound contains a planar aromatic ring, as does NAD+, but lacks a positive charge. PhAD is an inhibitor of horse liver alcohol dehydrogenase, competitive with NADH. PhAD is very similar to NAD+ sterically since both compounds have a planar aromatic ring. However, PhAD resembles NADH in binding to the enzyme because the dissociation constants of both compounds show a parallel increase as the pH is raised, whereas those of NAD+ behave in the opposite manner. These observations indicate that the enzyme differentiates between NAD+ and NADH on the basis of the positive charge on the molecule and not the stereochemical orientation of the reduced nicotinamide ring.", "contents": "The interaction of liver alcohol dehydrogenase with phenyl adenine dinucleotide, a novel analog of pyridine nucleotide coenzymes. We have synthesized phenyl adenine dinucleotide (P1-adenosine-5')-P2-(beta-D-ribofuranosylbenzene-5')-pyrophosphate (PhAD), a novel analog of pyridine nucleotide coenzymes. This compound contains a planar aromatic ring, as does NAD+, but lacks a positive charge. PhAD is an inhibitor of horse liver alcohol dehydrogenase, competitive with NADH. PhAD is very similar to NAD+ sterically since both compounds have a planar aromatic ring. However, PhAD resembles NADH in binding to the enzyme because the dissociation constants of both compounds show a parallel increase as the pH is raised, whereas those of NAD+ behave in the opposite manner. These observations indicate that the enzyme differentiates between NAD+ and NADH on the basis of the positive charge on the molecule and not the stereochemical orientation of the reduced nicotinamide ring."}
{"id": "PMID:210163", "title": "Purification and properties of spinach leaf cytoplasmic fructose-1,6-bisphosphatase.", "content": "Cytoplasmic fructose-1,6-bisphosphatase has been purified from spinach leaves to apparent homogeneity. The enzyme is a tetramer of molecular weight about 130,000. At pH 7.5, the Km for fructose 1.6-bisphosphate was 2.5 micron, and for MgCl2 0.13 mM; the enzyme was specific for fructose 1,6-bisphosphate. Saturation with Mg2+ was achieved with lower concentrations at pH 8 than at pH 7. AMP and high concentrations of fructose 1,6-bisphosphate inhibited enzyme activity. Ammonium sulfate relieved the latter inhibition but was itself inhibitory when substrate concentrations were low. Acetylation studies demonstrated that the AMP regulatory site was distinct from the catalytic site. Cytoplasmic fructose-1,6-bisphosphatase may contribute to the regulation of sucrose biosynthesis in plant leaves.", "contents": "Purification and properties of spinach leaf cytoplasmic fructose-1,6-bisphosphatase. Cytoplasmic fructose-1,6-bisphosphatase has been purified from spinach leaves to apparent homogeneity. The enzyme is a tetramer of molecular weight about 130,000. At pH 7.5, the Km for fructose 1.6-bisphosphate was 2.5 micron, and for MgCl2 0.13 mM; the enzyme was specific for fructose 1,6-bisphosphate. Saturation with Mg2+ was achieved with lower concentrations at pH 8 than at pH 7. AMP and high concentrations of fructose 1,6-bisphosphate inhibited enzyme activity. Ammonium sulfate relieved the latter inhibition but was itself inhibitory when substrate concentrations were low. Acetylation studies demonstrated that the AMP regulatory site was distinct from the catalytic site. Cytoplasmic fructose-1,6-bisphosphatase may contribute to the regulation of sucrose biosynthesis in plant leaves."}
{"id": "PMID:210164", "title": "Hepatic alpha-adrenergic receptors. Identification and subcellular localization using [3H]dihydroergocryptine.", "content": "Recently, several workers have shown that adrenergic control of hepatic carbohydrate metabolism has the characteristics of an alpha-receptor-mediated process. Using the rat liver membrane preparation of Neville (Neville, D. (1968) Biochim. Biophys. Acta 154, 540-552), alpha-adrenergic receptors have been identified using the ligand [3H]dihydroergocryptine. The receptors are saturable and of high affinity. Scatchard analysis yields a KD of 1.8 nM with 1.7 +/- 0.55 pmol of sites/mg of protein. Competition of dihydroergocryptine binding with various pharmacologic agents yields the typical (alpha-adrenergic potency series: (-)-epinephrine greater than (-)-norepinephrine greater than (-)-isoproterenol. (-)-Isomers are more potent than (+)-isomers. The alpha-blocker phentolamine is 3.4 orders of magnitude more potent than the beta-blocker propranolol. To determine subcellular localization of alpha-adrenergic receptors, livers were fractionated into a crude homogenate, a 1500 X g pellet, and the purified membrane preparation used previously for binding. Specific dihydroergocryptine binding, ouabain-inhibitable (Na,K)-ATPase, and F--stimulated adenylate cyclase activities, were followed in these fractions. Specific binding was enriched, relative to that in the crude homogenate, 2.88-fold in the pellet and 6.28-fold in the membranes. Similarly, (Na,K)-ATPase acticity was enriched 2.6-fold in the pellet and 7.1-fold in the membranes while adenylate cyclase activity was enriched 2.9-fold in the pellet and 3.5-fold in the membranes. It is concluded that hepatic alpha-adrenergic receptors are likely concentrated in the plasma membranes.", "contents": "Hepatic alpha-adrenergic receptors. Identification and subcellular localization using [3H]dihydroergocryptine. Recently, several workers have shown that adrenergic control of hepatic carbohydrate metabolism has the characteristics of an alpha-receptor-mediated process. Using the rat liver membrane preparation of Neville (Neville, D. (1968) Biochim. Biophys. Acta 154, 540-552), alpha-adrenergic receptors have been identified using the ligand [3H]dihydroergocryptine. The receptors are saturable and of high affinity. Scatchard analysis yields a KD of 1.8 nM with 1.7 +/- 0.55 pmol of sites/mg of protein. Competition of dihydroergocryptine binding with various pharmacologic agents yields the typical (alpha-adrenergic potency series: (-)-epinephrine greater than (-)-norepinephrine greater than (-)-isoproterenol. (-)-Isomers are more potent than (+)-isomers. The alpha-blocker phentolamine is 3.4 orders of magnitude more potent than the beta-blocker propranolol. To determine subcellular localization of alpha-adrenergic receptors, livers were fractionated into a crude homogenate, a 1500 X g pellet, and the purified membrane preparation used previously for binding. Specific dihydroergocryptine binding, ouabain-inhibitable (Na,K)-ATPase, and F--stimulated adenylate cyclase activities, were followed in these fractions. Specific binding was enriched, relative to that in the crude homogenate, 2.88-fold in the pellet and 6.28-fold in the membranes. Similarly, (Na,K)-ATPase acticity was enriched 2.6-fold in the pellet and 7.1-fold in the membranes while adenylate cyclase activity was enriched 2.9-fold in the pellet and 3.5-fold in the membranes. It is concluded that hepatic alpha-adrenergic receptors are likely concentrated in the plasma membranes."}
{"id": "PMID:210165", "title": "Conversion of glucose to sorbitol and fructose by liver-derived cells in culture.", "content": "Conversion of glucose to fructose and sorbitol is documented in rat hepatoma-derived cultured cells (HTC cells). After addition of 5.5 mM [U-14C]glucose to incubation medium, labeled sorbitol and fructose accumulated intracellularly at a linear rate over a period of 60 min. The sugars were isolated, identified, and quantitated by paper chromatography, gas-liquid chromatography, and enzymatic phosphorylation of fructose. Primary culture of adult rat hepatocytes was analyzed similarly and demonstrated no significant accumulation of labeled fructose or sorbitol. The basis for this difference between HTC cells and primary hepatocyte culture was examined both in terms of enzyme activities that mediate the formation of sorbitol and fructose and in terms of the catabolism of these sugars. Both types of culture (as well as extracts of intact rat liver) exhibited enzymatic activities catalyzing the conversion of glucose to sorbitol (aldose reductase) and sorbitol to fructose (sorbitol dehydrogenase). However, the cultures differed strikingly with regard to the catabolism of sorbitol and fructose. The conversion of labeled sorbitol to metabolites in HTC cells was negligible; by contrast, hepatocytes in primary culture utilized the sugars at rates comparable to that of glucose, which may account for the lack of their accumulation in primary culture. The findings suggest that the conversion of glucose to sorbitol and fructose by HTC cells may represent a retained normal liver function, one which is amplified by the inability of HTC cells to dispose of these sugars.", "contents": "Conversion of glucose to sorbitol and fructose by liver-derived cells in culture. Conversion of glucose to fructose and sorbitol is documented in rat hepatoma-derived cultured cells (HTC cells). After addition of 5.5 mM [U-14C]glucose to incubation medium, labeled sorbitol and fructose accumulated intracellularly at a linear rate over a period of 60 min. The sugars were isolated, identified, and quantitated by paper chromatography, gas-liquid chromatography, and enzymatic phosphorylation of fructose. Primary culture of adult rat hepatocytes was analyzed similarly and demonstrated no significant accumulation of labeled fructose or sorbitol. The basis for this difference between HTC cells and primary hepatocyte culture was examined both in terms of enzyme activities that mediate the formation of sorbitol and fructose and in terms of the catabolism of these sugars. Both types of culture (as well as extracts of intact rat liver) exhibited enzymatic activities catalyzing the conversion of glucose to sorbitol (aldose reductase) and sorbitol to fructose (sorbitol dehydrogenase). However, the cultures differed strikingly with regard to the catabolism of sorbitol and fructose. The conversion of labeled sorbitol to metabolites in HTC cells was negligible; by contrast, hepatocytes in primary culture utilized the sugars at rates comparable to that of glucose, which may account for the lack of their accumulation in primary culture. The findings suggest that the conversion of glucose to sorbitol and fructose by HTC cells may represent a retained normal liver function, one which is amplified by the inability of HTC cells to dispose of these sugars."}
{"id": "PMID:210167", "title": "5-Methylthioribose kinase. A new enzyme involved in the formation of methionine from 5-methylthioribose.", "content": "The presence of a previously unidentified enzyme, tentatively designated 5-methylthioribose kinase, has been demonstrated in cell-free extracts of Enterobacter aerogenes. The enzyme catalyzes the ATP-dependent phosphorylation of 5-methylthioribose. ADP is one of the products of the reaction and, based on functional group analyses, the other product is 5-methylthioribose 1-phosphate. A 40-fold purified enzyme preparation has been obtained from a cell-free extract of E. aerogenes. Activity of the partially purified enzyme is totally dependent on the presence of a divalent cation and a sulfhydryl reagent. The substrate specificity of the enzyme is quite narrow, and the Km values for ATP and 5-methylthioribose are 7.4 X 10(-5) M and 8.1 X 10(-6) M, respectively. These results suggest that 5-methylthioribose kinase may be a primary enzyme involved in the recycling of the methylthio group of 5-methylthioribose back into methionine.", "contents": "5-Methylthioribose kinase. A new enzyme involved in the formation of methionine from 5-methylthioribose. The presence of a previously unidentified enzyme, tentatively designated 5-methylthioribose kinase, has been demonstrated in cell-free extracts of Enterobacter aerogenes. The enzyme catalyzes the ATP-dependent phosphorylation of 5-methylthioribose. ADP is one of the products of the reaction and, based on functional group analyses, the other product is 5-methylthioribose 1-phosphate. A 40-fold purified enzyme preparation has been obtained from a cell-free extract of E. aerogenes. Activity of the partially purified enzyme is totally dependent on the presence of a divalent cation and a sulfhydryl reagent. The substrate specificity of the enzyme is quite narrow, and the Km values for ATP and 5-methylthioribose are 7.4 X 10(-5) M and 8.1 X 10(-6) M, respectively. These results suggest that 5-methylthioribose kinase may be a primary enzyme involved in the recycling of the methylthio group of 5-methylthioribose back into methionine."}
{"id": "PMID:210169", "title": "Glycopeptides derived from individual membrane glycoproteins from control and Rous sarcoma virus-transformed hamster fibroblasts.", "content": "The membrane glycoproteins from control (BHK21/C13) and Rous sarcoma virus-transformed (C13/B4) baby hamster kidney cells grown in medium containing [14C]- or D-[3H]glucosamine have been separated into two distinct classes: a phenol-soluble fraction and an aqueous fraction. The membrane glycoproteins from both BHK21/C13 and C13/B4 partitioned similarly into these two fractions. The phenol and aquesous-soluble glycoproteins differed in their sodium dodecyl sulfate-polyacrylamide gel profiles, polyacrylamide isoelectric focusing profiles, and glycopeptide distribution on Sephadex G-50. A number of aqueous and phenol-soluble glycoproteins from BHK21/C13 and C13/B4 cells were purified to near homogeneity by means of polyacrylamide electrophoresis and gel electrofocusing. These glycoproteins range in molecular weight from 179,000 to 31,000 and have isoelectric points of 7.5 to 3.0. Our results show that the pronase glycopeptides of 20 out of 24 homologous membrane glycoproteins of equivalent molecular weight and isoelectric point from BHK21/C13 and C13/B4 cells are dissimilar as measured by Sephadex G-50 gel filtration.", "contents": "Glycopeptides derived from individual membrane glycoproteins from control and Rous sarcoma virus-transformed hamster fibroblasts. The membrane glycoproteins from control (BHK21/C13) and Rous sarcoma virus-transformed (C13/B4) baby hamster kidney cells grown in medium containing [14C]- or D-[3H]glucosamine have been separated into two distinct classes: a phenol-soluble fraction and an aqueous fraction. The membrane glycoproteins from both BHK21/C13 and C13/B4 partitioned similarly into these two fractions. The phenol and aquesous-soluble glycoproteins differed in their sodium dodecyl sulfate-polyacrylamide gel profiles, polyacrylamide isoelectric focusing profiles, and glycopeptide distribution on Sephadex G-50. A number of aqueous and phenol-soluble glycoproteins from BHK21/C13 and C13/B4 cells were purified to near homogeneity by means of polyacrylamide electrophoresis and gel electrofocusing. These glycoproteins range in molecular weight from 179,000 to 31,000 and have isoelectric points of 7.5 to 3.0. Our results show that the pronase glycopeptides of 20 out of 24 homologous membrane glycoproteins of equivalent molecular weight and isoelectric point from BHK21/C13 and C13/B4 cells are dissimilar as measured by Sephadex G-50 gel filtration."}
{"id": "PMID:210173", "title": "Adenosine 3':5'-monophosphate receptor proteins in mammalian brain.", "content": "cAMP receptor proteins present in mammalian brain were identified and characterized with the use of the photoaffinity label 8-azido[32P]cAMP. Cytosol and membrane fractions from various regions of rat, guinea pig, and bovine brain contained two specific cAMP receptor proteins with apparent molecular weights of 47,000 and 52,000 to 55,000. Subcellular fractionation studies showed the highest amounts of these cAMP receptor proteins associated with cytosol fractions and synaptic membrane fractions. For both the cytosol and membrane fractions, the two cAMP receptor proteins represented almost all of the proteins specifically labeled by 8-azidol[32P]cAMP and appeared to be the regulatory subunits of cAMP-dependent protein kinases.", "contents": "Adenosine 3':5'-monophosphate receptor proteins in mammalian brain. cAMP receptor proteins present in mammalian brain were identified and characterized with the use of the photoaffinity label 8-azido[32P]cAMP. Cytosol and membrane fractions from various regions of rat, guinea pig, and bovine brain contained two specific cAMP receptor proteins with apparent molecular weights of 47,000 and 52,000 to 55,000. Subcellular fractionation studies showed the highest amounts of these cAMP receptor proteins associated with cytosol fractions and synaptic membrane fractions. For both the cytosol and membrane fractions, the two cAMP receptor proteins represented almost all of the proteins specifically labeled by 8-azidol[32P]cAMP and appeared to be the regulatory subunits of cAMP-dependent protein kinases."}
{"id": "PMID:210176", "title": "The use of orthacryl two-dimensional polyacrylamide gel electrophoresis to identify and compare the subunit polypeptides of bovine heart and yeast cytochrome c oxidases.", "content": "A two-dimensional electrophoretic method which takes advantage of the \"migration anomalies\" experienced by some polypeptides on gels of different porosities has been successfully used to resolve the seven subunit polypeptides of yeast cytochrome c oxidase and the nine polypeptides associated with bovine cytochrome c oxidase. The two-dimensional maps provided by this method reveal clear differences between these two cytochrome c oxidases.", "contents": "The use of orthacryl two-dimensional polyacrylamide gel electrophoresis to identify and compare the subunit polypeptides of bovine heart and yeast cytochrome c oxidases. A two-dimensional electrophoretic method which takes advantage of the \"migration anomalies\" experienced by some polypeptides on gels of different porosities has been successfully used to resolve the seven subunit polypeptides of yeast cytochrome c oxidase and the nine polypeptides associated with bovine cytochrome c oxidase. The two-dimensional maps provided by this method reveal clear differences between these two cytochrome c oxidases."}
{"id": "PMID:210177", "title": "Interaction of 125I-labeled Ca2+-dependent regulator protein with cyclic nucleotide phosphodiesterase and its inhibitory protein.", "content": "The Ca2+-dependent regulator protein of cyclic nucleotide phosphodiesterase was labeled with 125I to the extent of 1 mol of monoiodotyrosine per mol. The iodinated protein showed a small decrease in affinity for phosphodiesterase but gave the same maximal level of activation of the enzyme as did the unmodified regulator protein. Iodinated regulator protein formed complexes with both highly purified cyclic nucleotide phosphodiesterase and phosphodiesterase inhibitory protein in the presence but not in the absence of Ca2+ as demonstrated by ultracentrifugation in glycerol gradients. Cross-linking experiments indicate that the Ca2+-dependent regulator protein interacts with the large subunit of the inhibitory protein.", "contents": "Interaction of 125I-labeled Ca2+-dependent regulator protein with cyclic nucleotide phosphodiesterase and its inhibitory protein. The Ca2+-dependent regulator protein of cyclic nucleotide phosphodiesterase was labeled with 125I to the extent of 1 mol of monoiodotyrosine per mol. The iodinated protein showed a small decrease in affinity for phosphodiesterase but gave the same maximal level of activation of the enzyme as did the unmodified regulator protein. Iodinated regulator protein formed complexes with both highly purified cyclic nucleotide phosphodiesterase and phosphodiesterase inhibitory protein in the presence but not in the absence of Ca2+ as demonstrated by ultracentrifugation in glycerol gradients. Cross-linking experiments indicate that the Ca2+-dependent regulator protein interacts with the large subunit of the inhibitory protein."}
{"id": "PMID:210179", "title": "The K+/site and H+/site stoichiometry of mitochondrial electron transport.", "content": "Electrode measurements of the average number of H+ ejected and K+ taken up (in the presence of valinomycin) per pair of electrons passing the energy-conserving sites of the respiratory chain of rat liver and rat heart mitochondria have given identical values of the H+/site and 5+/site ratios very close to 4 in the presence of N-ethylmaleimide, an inhibitor of interfering respiration-coupled uptake of H+ + H2PO4-. The K+/site uptake ratio of 4 not only shows that inward movement of K+ provides quantitative charge-compensation for the 4 H+ ejected, but also confirms that 4 charges are separated per pair of electrons per site. When N-ethylmaleimide is omitted, the H+/site ejection ratio is depressed, because of the interfering secondary uptake of H/+ with H2PO4- on the phosphate carrier, but the K+/site uptake ratio remains at 4.0. Addition of phosphate or acetate, which can carry H+ into respiring mitochondria, further depresses the H+/site ratio, but does not affect the K+/site ratio, which remains at 4.0. These and other considerations thus confirm our earlier stoichiometric measurements that the average H+/site ratio is 4.0 and also show that the K+/site uptake ratio can be used as a measure of the intrinsic H+/site ratio, regardless of the presence of phosphate in the medium and without the necessity of adding N-ethylmaleimide or other inhibitors of H+ + H2PO4- transport.", "contents": "The K+/site and H+/site stoichiometry of mitochondrial electron transport. Electrode measurements of the average number of H+ ejected and K+ taken up (in the presence of valinomycin) per pair of electrons passing the energy-conserving sites of the respiratory chain of rat liver and rat heart mitochondria have given identical values of the H+/site and 5+/site ratios very close to 4 in the presence of N-ethylmaleimide, an inhibitor of interfering respiration-coupled uptake of H+ + H2PO4-. The K+/site uptake ratio of 4 not only shows that inward movement of K+ provides quantitative charge-compensation for the 4 H+ ejected, but also confirms that 4 charges are separated per pair of electrons per site. When N-ethylmaleimide is omitted, the H+/site ejection ratio is depressed, because of the interfering secondary uptake of H/+ with H2PO4- on the phosphate carrier, but the K+/site uptake ratio remains at 4.0. Addition of phosphate or acetate, which can carry H+ into respiring mitochondria, further depresses the H+/site ratio, but does not affect the K+/site ratio, which remains at 4.0. These and other considerations thus confirm our earlier stoichiometric measurements that the average H+/site ratio is 4.0 and also show that the K+/site uptake ratio can be used as a measure of the intrinsic H+/site ratio, regardless of the presence of phosphate in the medium and without the necessity of adding N-ethylmaleimide or other inhibitors of H+ + H2PO4- transport."}
{"id": "PMID:210180", "title": "A reassessment of structure-function relationships in glucagon. Glucagon1-21 is a full agonist.", "content": "Glucagon1-21 has been prepared by treating native glucagon with carboxypeptidase A. Purified glucagon1-21 did not contain detectable methionine (less than 0.001 residue/mol) and the activity of the compound did not change after treatment with cyanogen bromide as has been shown with native glucagon. Glucagon1-21 stimulates hepatic adenylate cyclase activity to the same extent as native glucagon but with 0.1% the potency. Glucagon1-21 also displayed 0.1% the binding affinity of native glucagon to the glucagon receptor in hepatic membranes. Glucagon22-29 alone or in combination with glucagon1-21 did not activate adenylate cyclase or displase 125I-glucagon from its receptor. The finding that glucagon1-21 is a full agonist on adenylate cyclase is discussed in relation to the structure-function relationships required for the biological action of glucagon.", "contents": "A reassessment of structure-function relationships in glucagon. Glucagon1-21 is a full agonist. Glucagon1-21 has been prepared by treating native glucagon with carboxypeptidase A. Purified glucagon1-21 did not contain detectable methionine (less than 0.001 residue/mol) and the activity of the compound did not change after treatment with cyanogen bromide as has been shown with native glucagon. Glucagon1-21 stimulates hepatic adenylate cyclase activity to the same extent as native glucagon but with 0.1% the potency. Glucagon1-21 also displayed 0.1% the binding affinity of native glucagon to the glucagon receptor in hepatic membranes. Glucagon22-29 alone or in combination with glucagon1-21 did not activate adenylate cyclase or displase 125I-glucagon from its receptor. The finding that glucagon1-21 is a full agonist on adenylate cyclase is discussed in relation to the structure-function relationships required for the biological action of glucagon."}
{"id": "PMID:210183", "title": "Reconstitution of hormone-sensitive adenylate cyclase activity with resolved components of the enzyme.", "content": "Adenylate cyclase can be resolved into at least two proteins, a thermolabile, N-ethylmaleimide-sensitive component and a second protein (or proteins) that is more stable to either of these treatments. Neither component by itself catalyzes the formation of cyclic AMP using MgATP as substrate. However, mixture of the two reconstitutes MgATP-dependent fluoride- and guanyl-5'-yl imidodiphosphate (Gpp(NH)p)-stimulatable adenylate cyclase activity. The more stable component can be resolved from the first in various tissues or cultured cells by treatment of membrnes or detergent extracts with heat or N-ethylmaleimide. The two proteins have also been resolved genetically in two clonal cell lines that are deficient in adenylate cyclase activity. An adenylate cyclase-deficient variant of the S49 lymphoma cell (AC-) contains only the thermolabile activity, while the activity of the more stable protein is found in a complementary hepatoma cell line (HC-1). In addition, AC-S49 cell plasma membranes contain MnATP-dependent adenylate cyclase activity. The protein that catalyzes this reaction appears to be the same as that which can combine with the thermostable component to reconstitute Mg2+-dependent enzyme activity because both activities co-fractionate by gel exclusion chromatography and sucrose density  gradient centrifugation, both activities have identical denaturation kinetics at 30 degrees C, and both activities are stabilized at 30 degrees C and labilized at 0 degree C by various nucleotides and divalent cations with similar specificity. It is thus hypothesized that the thermolabile factor is the catalytic subunit of the physiological adenylate cyclase and that the Mn2+-dependent activity is a nonphysiological expression of the catalytic protein. The thermostable moiety of the enzyme, which is proposed to serve a regulatory function, appears to consist of two functional components, based upon differential thermal lability of its ability to reconstitute hormone-, NaF-, or Gpp(NH)p-stimulated adenylate cyclase activity. These components have not, however, been physically separated. The thermolabile and thermostable components can interact in detergent solution or in a suitable membrane. Mixing of the detergent-solubilized regulatory component with AC-membranes that contain only the catalytic protein and beta-adrenergic receptors reconstitutes catecholamine-stimulatable adenylate cyclase activity; however, addition of the catalytic protein to membranes that contain receptor and the regulatory component yields MgATP-dependent enzymatic activity that is unresponsive to hormone.", "contents": "Reconstitution of hormone-sensitive adenylate cyclase activity with resolved components of the enzyme. Adenylate cyclase can be resolved into at least two proteins, a thermolabile, N-ethylmaleimide-sensitive component and a second protein (or proteins) that is more stable to either of these treatments. Neither component by itself catalyzes the formation of cyclic AMP using MgATP as substrate. However, mixture of the two reconstitutes MgATP-dependent fluoride- and guanyl-5'-yl imidodiphosphate (Gpp(NH)p)-stimulatable adenylate cyclase activity. The more stable component can be resolved from the first in various tissues or cultured cells by treatment of membrnes or detergent extracts with heat or N-ethylmaleimide. The two proteins have also been resolved genetically in two clonal cell lines that are deficient in adenylate cyclase activity. An adenylate cyclase-deficient variant of the S49 lymphoma cell (AC-) contains only the thermolabile activity, while the activity of the more stable protein is found in a complementary hepatoma cell line (HC-1). In addition, AC-S49 cell plasma membranes contain MnATP-dependent adenylate cyclase activity. The protein that catalyzes this reaction appears to be the same as that which can combine with the thermostable component to reconstitute Mg2+-dependent enzyme activity because both activities co-fractionate by gel exclusion chromatography and sucrose density  gradient centrifugation, both activities have identical denaturation kinetics at 30 degrees C, and both activities are stabilized at 30 degrees C and labilized at 0 degree C by various nucleotides and divalent cations with similar specificity. It is thus hypothesized that the thermolabile factor is the catalytic subunit of the physiological adenylate cyclase and that the Mn2+-dependent activity is a nonphysiological expression of the catalytic protein. The thermostable moiety of the enzyme, which is proposed to serve a regulatory function, appears to consist of two functional components, based upon differential thermal lability of its ability to reconstitute hormone-, NaF-, or Gpp(NH)p-stimulated adenylate cyclase activity. These components have not, however, been physically separated. The thermolabile and thermostable components can interact in detergent solution or in a suitable membrane. Mixing of the detergent-solubilized regulatory component with AC-membranes that contain only the catalytic protein and beta-adrenergic receptors reconstitutes catecholamine-stimulatable adenylate cyclase activity; however, addition of the catalytic protein to membranes that contain receptor and the regulatory component yields MgATP-dependent enzymatic activity that is unresponsive to hormone."}
{"id": "PMID:210185", "title": "Characterization of functional receptors for somatostatin in rat pituitary cells in culture.", "content": "GH4C1 cells are a clonal strain of rat pituitary tumor cells which synthesize and secrete prolactin and growth hormone. Somatostatin, a  hypothalamic tetradecapeptide, inhibits the release of growth hormone and, under certain circumstances, also prolactin from normal pituitary cells. We have prepared [125I-Tyr1]somatostatin (approximately 2200 C1/mmol) and have shown that this ligand binds to a limited number of high affinity sites on GH4C1 cells. Half-maximal binding of somatostatin occurred at a concentration of 6 x 10(-10) M. A maximum of 0.11 pmol of [125I-Tyr1]somatostatin was bound per mg of cell protein, equivalent to 13,000 receptor sites per cell. The rate constant for binding (kon) was 8 x 10(7) M(-1) min(-1). The rate constant for dissociation (koff) was determined by direct measurement to be 0.02 min(-1) both in the presence and absence of excess nonradioactive somatostatin. Binding of [125I-Tyr1]somatostatin was not inhibited by 10(-7) M thyrotropin-releasing hormones. Substance P, neurotensin, luteinizing hormone-releasing hormone, calcitonin, adrenocorticotropin, or insulin. Of seven nonpituitary cell lines tested, none had specific receptors for somatostatin. Somatostatin was shown to inhibit prolactin and growth hormone production by CH4C1 cells. The dose-response characteristics for binding and the biological actions of somatostatin were essentially coincident. Furthermore, among several clonal pituitary cell strains tested, only those which had receptors for somatostatin showed a biological response to the hormone. We conclude that the characterized somatostatin receptor is necessary for the biological actions of somatostatin on GH4C1 cells.", "contents": "Characterization of functional receptors for somatostatin in rat pituitary cells in culture. GH4C1 cells are a clonal strain of rat pituitary tumor cells which synthesize and secrete prolactin and growth hormone. Somatostatin, a  hypothalamic tetradecapeptide, inhibits the release of growth hormone and, under certain circumstances, also prolactin from normal pituitary cells. We have prepared [125I-Tyr1]somatostatin (approximately 2200 C1/mmol) and have shown that this ligand binds to a limited number of high affinity sites on GH4C1 cells. Half-maximal binding of somatostatin occurred at a concentration of 6 x 10(-10) M. A maximum of 0.11 pmol of [125I-Tyr1]somatostatin was bound per mg of cell protein, equivalent to 13,000 receptor sites per cell. The rate constant for binding (kon) was 8 x 10(7) M(-1) min(-1). The rate constant for dissociation (koff) was determined by direct measurement to be 0.02 min(-1) both in the presence and absence of excess nonradioactive somatostatin. Binding of [125I-Tyr1]somatostatin was not inhibited by 10(-7) M thyrotropin-releasing hormones. Substance P, neurotensin, luteinizing hormone-releasing hormone, calcitonin, adrenocorticotropin, or insulin. Of seven nonpituitary cell lines tested, none had specific receptors for somatostatin. Somatostatin was shown to inhibit prolactin and growth hormone production by CH4C1 cells. The dose-response characteristics for binding and the biological actions of somatostatin were essentially coincident. Furthermore, among several clonal pituitary cell strains tested, only those which had receptors for somatostatin showed a biological response to the hormone. We conclude that the characterized somatostatin receptor is necessary for the biological actions of somatostatin on GH4C1 cells."}
{"id": "PMID:210189", "title": "Nucleotide sequence studies of polyoma DNA. The Hpa II 3/5 junction to the Hpa II 4/Hae III 18 junction, encoding the origin of DNA replication and the 5' end of the early region.", "content": "The nucleotide sequence of polyoma DNA, from near the Hpa II 3/5 unction to the Hpa II 4/ae III 18 junction has been determined by the chemical method of Maxam and Gilbert (Maxam, A., and Gilbert, W. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 560--564). The sequence contains 878 base paris, including the origin of DNA replication and the region known to encode the hr-t function. The region corresponding to the origin of DNA replication contains several short-repeated sequences and palindromes. There is a 30-base-pair region with striking similarity to the corresponding region of SV40, and, as in SV40, a portion of that sequence is capable of forming a stable hairpin loop. In the region encoding the hr-t function, there is apparently a single open reading frame extending from position 188 to theHpa III 4/Hae III 18 junction. The potential translation product of this open frame begins with an initiation codon starting at position 188, and the first five amino acids of this product are Met-Asp-Arg-Val-Leu. This sequence is similar to the NH2-terminal five amino acids of SV40 small t-antigen known from nucleotide and amino acid sequencing to be Met-Asp-Lys-Val-Leu.", "contents": "Nucleotide sequence studies of polyoma DNA. The Hpa II 3/5 junction to the Hpa II 4/Hae III 18 junction, encoding the origin of DNA replication and the 5' end of the early region. The nucleotide sequence of polyoma DNA, from near the Hpa II 3/5 unction to the Hpa II 4/ae III 18 junction has been determined by the chemical method of Maxam and Gilbert (Maxam, A., and Gilbert, W. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 560--564). The sequence contains 878 base paris, including the origin of DNA replication and the region known to encode the hr-t function. The region corresponding to the origin of DNA replication contains several short-repeated sequences and palindromes. There is a 30-base-pair region with striking similarity to the corresponding region of SV40, and, as in SV40, a portion of that sequence is capable of forming a stable hairpin loop. In the region encoding the hr-t function, there is apparently a single open reading frame extending from position 188 to theHpa III 4/Hae III 18 junction. The potential translation product of this open frame begins with an initiation codon starting at position 188, and the first five amino acids of this product are Met-Asp-Arg-Val-Leu. This sequence is similar to the NH2-terminal five amino acids of SV40 small t-antigen known from nucleotide and amino acid sequencing to be Met-Asp-Lys-Val-Leu."}
{"id": "PMID:210192", "title": "Dissociation between rate of hepatic lipoprotein secretion and hepatocyte microtubule content.", "content": "The fact that colchicines inhibits hepatic secretion of very low density lipoprotein (VLDL) particles has been interpreted to mean that microtubules are involved in hepatic VLDL secretion. To further define this relationship, we have attempted to see if changes in hepatic VLDL secretion are associated with changes in hepatocyte microtubule or tubulin content. Accordingly, hepatic secretion of VLDL was increased in rats, and the hepatocyte content of both microtubules (using quantitative morphometric methods) and tubulin (using a time-decay colchicine binding assay) was determined. In acute experiments, VLDL secretion was increased by perfusion of isolated rat livers for 2 h with varying concentrations of free fatty acids (FFA). Results indicate that hepatic VLDL triglyceride (TG) secretion at perfusate FFA levels of 0.7 muEq/ml is threefold greater (P < 0.01) than when livers are perfused without added FFA. However, no differences are observed in the content of microtubules in these livers: specifically, microtubules occupy 0.029 percent of hepatocyte cytoplasm in livers perfused without FFA and 0.030 percent of cytoplasm in livers perfused with FFA. In chronic experiments, rats were fed for 1 wk with either standard rat chow or a hyperlipidemic (sucrose/lard) diet. With the experimental diet, plasma triglyceride levels increase threefold over controls, and liver VLDL-TG production, as determined by [(3)H]glycerol turnover studies, is 55 percent greater (P < 0.01) than controls. However, microtubules occupy 0.027 percent of the cytoplasm of hepatocyte cytoplasm whether rats are on standard or hyperlipidemic diets. Furthermore, the tubulin content of isolated hepatocytes does change, and represents 1 percent of hepatocyte soluble protein, irrespective of diet. These results suggest that increases in hepatic VLDL secretion can occur without any demonstrable change in hepatocyte assembled microtubule or tubulin content, and raise questions as to the role played by microtubules in hepatic VLDL secretion.", "contents": "Dissociation between rate of hepatic lipoprotein secretion and hepatocyte microtubule content. The fact that colchicines inhibits hepatic secretion of very low density lipoprotein (VLDL) particles has been interpreted to mean that microtubules are involved in hepatic VLDL secretion. To further define this relationship, we have attempted to see if changes in hepatic VLDL secretion are associated with changes in hepatocyte microtubule or tubulin content. Accordingly, hepatic secretion of VLDL was increased in rats, and the hepatocyte content of both microtubules (using quantitative morphometric methods) and tubulin (using a time-decay colchicine binding assay) was determined. In acute experiments, VLDL secretion was increased by perfusion of isolated rat livers for 2 h with varying concentrations of free fatty acids (FFA). Results indicate that hepatic VLDL triglyceride (TG) secretion at perfusate FFA levels of 0.7 muEq/ml is threefold greater (P < 0.01) than when livers are perfused without added FFA. However, no differences are observed in the content of microtubules in these livers: specifically, microtubules occupy 0.029 percent of hepatocyte cytoplasm in livers perfused without FFA and 0.030 percent of cytoplasm in livers perfused with FFA. In chronic experiments, rats were fed for 1 wk with either standard rat chow or a hyperlipidemic (sucrose/lard) diet. With the experimental diet, plasma triglyceride levels increase threefold over controls, and liver VLDL-TG production, as determined by [(3)H]glycerol turnover studies, is 55 percent greater (P < 0.01) than controls. However, microtubules occupy 0.027 percent of the cytoplasm of hepatocyte cytoplasm whether rats are on standard or hyperlipidemic diets. Furthermore, the tubulin content of isolated hepatocytes does change, and represents 1 percent of hepatocyte soluble protein, irrespective of diet. These results suggest that increases in hepatic VLDL secretion can occur without any demonstrable change in hepatocyte assembled microtubule or tubulin content, and raise questions as to the role played by microtubules in hepatic VLDL secretion."}
{"id": "PMID:210193", "title": "Microtubules and cyclic AMP in human leukocytes: on the order of things.", "content": "We have shown previously that the beta-adrenergic agonist isoproterenol (2muM) and the phosphodiesterase inhibitor isobutylmethylxanthine (1 mM) produce a much greater increase in cyclic AMP in human leukocytes that have been pretreated with colchicine (or with other agents that affect microtubule assembly) than in control leukocytes. The effects of colchicines were both time- and dose-dependant. These and other data suggested that the generation of cyclic AMP is normally restricted by an intact system of cytoplasmic microtubules. If so, then the same time and dose dependencies might apply to other colchicines-induced changes in leukocyte function. We have now assayed the distribution of concanavalin A (Con A)-receptor complexes on the leukocyte membrane, taking into account that leukocytes competent to assemble microtubules show a uniform distribution of surface- bound Con A whereas microtubule-deficient cells accumulate Con A in surface caps. We have found that the effect of colchicine on capping is also both time- and dose dependent, and that the dose-response relationships conform to those required to increase cyclic AMP levels. These findings provide further evidence that both colchicine-induced Con-A capping and colchicine- induced cyclic AMP generation depend upon the relaxation of constraints normally imposed by cytoplasmic microtubules upon the plasma membrane, which limit, respectively, lateral mobility of the lectin-receptor complexes, and expression of hormone-sensitive adenylate cyclase. Moreover, colchicine-induced Con-A cap formation is not affected even by very large changes in leukocyte cyclic AMP levels. Thus, elevated cyclic AMP levels do not appear to promote the dissolution of microtubules; rather, the dissolution of microtubules permits the generation of increased amounts of cyclic AMP.", "contents": "Microtubules and cyclic AMP in human leukocytes: on the order of things. We have shown previously that the beta-adrenergic agonist isoproterenol (2muM) and the phosphodiesterase inhibitor isobutylmethylxanthine (1 mM) produce a much greater increase in cyclic AMP in human leukocytes that have been pretreated with colchicine (or with other agents that affect microtubule assembly) than in control leukocytes. The effects of colchicines were both time- and dose-dependant. These and other data suggested that the generation of cyclic AMP is normally restricted by an intact system of cytoplasmic microtubules. If so, then the same time and dose dependencies might apply to other colchicines-induced changes in leukocyte function. We have now assayed the distribution of concanavalin A (Con A)-receptor complexes on the leukocyte membrane, taking into account that leukocytes competent to assemble microtubules show a uniform distribution of surface- bound Con A whereas microtubule-deficient cells accumulate Con A in surface caps. We have found that the effect of colchicine on capping is also both time- and dose dependent, and that the dose-response relationships conform to those required to increase cyclic AMP levels. These findings provide further evidence that both colchicine-induced Con-A capping and colchicine- induced cyclic AMP generation depend upon the relaxation of constraints normally imposed by cytoplasmic microtubules upon the plasma membrane, which limit, respectively, lateral mobility of the lectin-receptor complexes, and expression of hormone-sensitive adenylate cyclase. Moreover, colchicine-induced Con-A cap formation is not affected even by very large changes in leukocyte cyclic AMP levels. Thus, elevated cyclic AMP levels do not appear to promote the dissolution of microtubules; rather, the dissolution of microtubules permits the generation of increased amounts of cyclic AMP."}
{"id": "PMID:210194", "title": "Sex differences among clients of an emergency care unit for alcoholism.", "content": "Compared male and female clients of an emergency care unit for the treatment of alcohol-related crises on a number of basic characteristics and procedural variables. Female clients were found to be significantly younger and more likely to be employed than males. The two groups did not differ reliably with respect to educational level or marital status. Females were found to be referred to the center by Alcoholics Anonymous and family members more often than were male clients, and male clients were referred more often by police than were female clients. The two groups also differed with respect to disposition at time of discharge, with more females judged as not needing additional treatment and more males viewed as needing additional treatment, but family or patient was not ready at the time.", "contents": "Sex differences among clients of an emergency care unit for alcoholism. Compared male and female clients of an emergency care unit for the treatment of alcohol-related crises on a number of basic characteristics and procedural variables. Female clients were found to be significantly younger and more likely to be employed than males. The two groups did not differ reliably with respect to educational level or marital status. Females were found to be referred to the center by Alcoholics Anonymous and family members more often than were male clients, and male clients were referred more often by police than were female clients. The two groups also differed with respect to disposition at time of discharge, with more females judged as not needing additional treatment and more males viewed as needing additional treatment, but family or patient was not ready at the time."}
{"id": "PMID:210195", "title": "A smoking satiation procedure with reduced medical risk.", "content": "Tested the efficacy of a smoking satiation procedure with reduced medical risk. As predicted, experimental taste satiation (holding smoke in the mouth with occasional inhalations) suppressed habitual smoking as effectively as rapid smoking satiation. In view of the extensive relapse problems that follow the singular application of aversive conditioning procedures, follow-up hypnosis and counseling treatments were applied in order to assist Ss in maintaining smoking cessation. At the time of the 6-month follow-up contact, confirmed abstinence reports for 66% of all Ss who received treatment were obtained.", "contents": "A smoking satiation procedure with reduced medical risk. Tested the efficacy of a smoking satiation procedure with reduced medical risk. As predicted, experimental taste satiation (holding smoke in the mouth with occasional inhalations) suppressed habitual smoking as effectively as rapid smoking satiation. In view of the extensive relapse problems that follow the singular application of aversive conditioning procedures, follow-up hypnosis and counseling treatments were applied in order to assist Ss in maintaining smoking cessation. At the time of the 6-month follow-up contact, confirmed abstinence reports for 66% of all Ss who received treatment were obtained."}
{"id": "PMID:210196", "title": "Internal organization of membranes at end bulbs of Held in the anteroventral cochlear nucleus.", "content": "The end of bulb of Held in the rostral ventral cochlear nucleus of the chinchilla and guinea pig was studied with the freeze-fracture technique. The end bulb has multiple, small active zones which are uniformly distributed within the calyceal portion of this terminal. Single or small groups of active zones are surrounded by enlarged channels of extracellular space often containing processes of astrocytes. Small plasmalemmal deformations occur at these active zones. The number of these deformations is thought to be indicative of exocytotic transmitter release because they are more frequent in animals fixed in a noisy environment compared to animals fixed in a quiet environment. Thus, our study provides a basis for the quantitative study of changes in transmitter secretion at a central nervous system synapse driven by a controllable natural stimulus. The postsynaptic active zone at end bulbs resembles other excitatory synapses in the central nervous system in having an aggregate of large particles on the external membrane leaflet. This junctional aggregate of particles is coextensive with the presynaptic active zone and with the postsynaptic density seen in thin sections. Several perisynaptic aggregates of particles are deployed around each active zone on the external membrane leaflet. These irregularly-shaped aggregates occur preferentially opposite the channels of enlarged extracellular space and along the edge of the end bulb and are not components of intercellular junctions or plasmalemmal contacts with cytoplasmic organelles. Although the function of the different particle aggregates on the postsynaptic membrane is not clear, our findings provide a basis for studying the factors controlling and maintaining their structure as well as more evidence that a consistent relationship exists between types of synaptic action and structure of the postsynaptic membrane.", "contents": "Internal organization of membranes at end bulbs of Held in the anteroventral cochlear nucleus. The end of bulb of Held in the rostral ventral cochlear nucleus of the chinchilla and guinea pig was studied with the freeze-fracture technique. The end bulb has multiple, small active zones which are uniformly distributed within the calyceal portion of this terminal. Single or small groups of active zones are surrounded by enlarged channels of extracellular space often containing processes of astrocytes. Small plasmalemmal deformations occur at these active zones. The number of these deformations is thought to be indicative of exocytotic transmitter release because they are more frequent in animals fixed in a noisy environment compared to animals fixed in a quiet environment. Thus, our study provides a basis for the quantitative study of changes in transmitter secretion at a central nervous system synapse driven by a controllable natural stimulus. The postsynaptic active zone at end bulbs resembles other excitatory synapses in the central nervous system in having an aggregate of large particles on the external membrane leaflet. This junctional aggregate of particles is coextensive with the presynaptic active zone and with the postsynaptic density seen in thin sections. Several perisynaptic aggregates of particles are deployed around each active zone on the external membrane leaflet. These irregularly-shaped aggregates occur preferentially opposite the channels of enlarged extracellular space and along the edge of the end bulb and are not components of intercellular junctions or plasmalemmal contacts with cytoplasmic organelles. Although the function of the different particle aggregates on the postsynaptic membrane is not clear, our findings provide a basis for studying the factors controlling and maintaining their structure as well as more evidence that a consistent relationship exists between types of synaptic action and structure of the postsynaptic membrane."}
{"id": "PMID:210197", "title": "Melanoacanthoma. Ultrastructural and immunological studies.", "content": "Electronmicroscopic studies confirmed that melanoacanthoma is a non-nevoid elevated epithelial tumor composed of keratinocytes of both basaloid and spinous differentiation and of large dentritic melanocytes. The block in transfer of pigment from melanocytes to keratinocytes was found not to be complete. Langerhans cells, present in the malpighian layers were normal in morphology. Immunofluorescent studies and an immunoprecipitin assay also showed our patient's melanoacanthoma not to be related to malignant melanoma.", "contents": "Melanoacanthoma. Ultrastructural and immunological studies. Electronmicroscopic studies confirmed that melanoacanthoma is a non-nevoid elevated epithelial tumor composed of keratinocytes of both basaloid and spinous differentiation and of large dentritic melanocytes. The block in transfer of pigment from melanocytes to keratinocytes was found not to be complete. Langerhans cells, present in the malpighian layers were normal in morphology. Immunofluorescent studies and an immunoprecipitin assay also showed our patient's melanoacanthoma not to be related to malignant melanoma."}
{"id": "PMID:210198", "title": "An ultrastructural study of the formation of \"dark\" and \"light\" cytoplasmic inclusions by murine cytomegalovirus in mouse submandibular gland.", "content": "Electron micrographs of acinar cells of the submandibular glands of CFW mice infected with murine cytomegalovirus, Smith strain, were studied. The resulting viral intracytoplasmic inclusion bodies were classified into two groups termed \"light\" (relatively electron-lucent) and \"dark\" (relatively electron-dense). It appeared that the \"dark\" type was the late stage of inclusion body maturation.", "contents": "An ultrastructural study of the formation of \"dark\" and \"light\" cytoplasmic inclusions by murine cytomegalovirus in mouse submandibular gland. Electron micrographs of acinar cells of the submandibular glands of CFW mice infected with murine cytomegalovirus, Smith strain, were studied. The resulting viral intracytoplasmic inclusion bodies were classified into two groups termed \"light\" (relatively electron-lucent) and \"dark\" (relatively electron-dense). It appeared that the \"dark\" type was the late stage of inclusion body maturation."}
{"id": "PMID:210200", "title": "Enhanced collagenase activity in diabetic rat gingiva: in vitro and in vivo evidence.", "content": "Gingiva from alloxan and streptozotocin-diabetic rats exhibited markedly enhanced collagenolytic activity in tissue culture. This effect was eliminated by puromycin or by repeated freeze-thawing of the tissue prior to incubation. Soluble extracts of the diabetic gingiva in situ were found to contain breakdown products of collagen similar in size to the reaction products generated by tissue collagenase. These fragments were not detected in the control tissue. This study indicates that experimental diabetes stimulates the synthesis of gingival collagenase in culture and that a similar effect occurs in vivo.", "contents": "Enhanced collagenase activity in diabetic rat gingiva: in vitro and in vivo evidence. Gingiva from alloxan and streptozotocin-diabetic rats exhibited markedly enhanced collagenolytic activity in tissue culture. This effect was eliminated by puromycin or by repeated freeze-thawing of the tissue prior to incubation. Soluble extracts of the diabetic gingiva in situ were found to contain breakdown products of collagen similar in size to the reaction products generated by tissue collagenase. These fragments were not detected in the control tissue. This study indicates that experimental diabetes stimulates the synthesis of gingival collagenase in culture and that a similar effect occurs in vivo."}
{"id": "PMID:210201", "title": "Microleakage of several class V anterior restorative materials: a laboratory study.", "content": "The study was designed to evaluate the marginal leakage of abraded gingival areas in extracted teeth using five anterior composite resin acid-etch restorative materials and a glass ionomer cement, ASPA. In using three of the composite resin restorative materials, Simulate, Cervident, and Concise, there was a layer of unfilled resin between the etched tooth surface and the composite resin. Restodent and Enamelite were placed directly on the etched tooth surface. The results of the study indicate that there is a significantly greater degree of marginal leakage at the gingival margin than there is at the occlusal or incisal margin of composite restorations. In addition, greater marginal leakage was observed in those restorations where no layer of unfilled resin was placed between the etched tooth surface and the composite resin. The glass ionomer cement showed no marginal leakage at intervals of one day, three months, and six months; however, a small amount of leakage was observed at the incisal or occlusal and gingival margins at a year on half of the autoradiographs. A study has been initiated to determine leakage patterns around composite resin restorations placed in teeth with naturally occurring cervical erosion or abrasion.", "contents": "Microleakage of several class V anterior restorative materials: a laboratory study. The study was designed to evaluate the marginal leakage of abraded gingival areas in extracted teeth using five anterior composite resin acid-etch restorative materials and a glass ionomer cement, ASPA. In using three of the composite resin restorative materials, Simulate, Cervident, and Concise, there was a layer of unfilled resin between the etched tooth surface and the composite resin. Restodent and Enamelite were placed directly on the etched tooth surface. The results of the study indicate that there is a significantly greater degree of marginal leakage at the gingival margin than there is at the occlusal or incisal margin of composite restorations. In addition, greater marginal leakage was observed in those restorations where no layer of unfilled resin was placed between the etched tooth surface and the composite resin. The glass ionomer cement showed no marginal leakage at intervals of one day, three months, and six months; however, a small amount of leakage was observed at the incisal or occlusal and gingival margins at a year on half of the autoradiographs. A study has been initiated to determine leakage patterns around composite resin restorations placed in teeth with naturally occurring cervical erosion or abrasion."}
{"id": "PMID:210232", "title": "Target antigens for H-2-restricted vesicular stomatitis virus-specific cytotoxic T cells.", "content": "Cytotoxic thymus-derived lymphocytes from mice infected with vesicular stomatitis virus (VSV) are H-2 restricted and virus specific for the Indiana and New Jersey strains of VSV. VSV-Indiana-immune T cells can lyse target cells infected with the temperature sensitive (ts) mutant ts 045 about 30 times better when target cell infection occurs at the permissive rather than the non-permissive temperature. Since this mutant fails to express the glycoprotein at the cell surface when grown at the nonpermissive temperature, our results support the view that the viral glycoprotein is involved in defining the major target antigen for VSV-specific T cells. However, the tl 17 mutant that expresses a mutant glycoprotein at the cell surface was lysed, suggesting that the expressed mutated glycoprotein can cross-react with Indiana wild-type glycoprotein. Targets infected at the nonpermissive temperature with VSV ts G31 (mutant in the matrix protein) are still susceptible to T cell-mediated lysis but at a lower level of sensitivity. These results are compatible with the interpretation that for VSV-specific T cell lysis of infected target cells, the viral glycoprotein is a major target antigen and must be expressed, and that the matrix protein plays a lesser role, probably by indirectly influencing glycoprotein configuration at the cell surface.", "contents": "Target antigens for H-2-restricted vesicular stomatitis virus-specific cytotoxic T cells. Cytotoxic thymus-derived lymphocytes from mice infected with vesicular stomatitis virus (VSV) are H-2 restricted and virus specific for the Indiana and New Jersey strains of VSV. VSV-Indiana-immune T cells can lyse target cells infected with the temperature sensitive (ts) mutant ts 045 about 30 times better when target cell infection occurs at the permissive rather than the non-permissive temperature. Since this mutant fails to express the glycoprotein at the cell surface when grown at the nonpermissive temperature, our results support the view that the viral glycoprotein is involved in defining the major target antigen for VSV-specific T cells. However, the tl 17 mutant that expresses a mutant glycoprotein at the cell surface was lysed, suggesting that the expressed mutated glycoprotein can cross-react with Indiana wild-type glycoprotein. Targets infected at the nonpermissive temperature with VSV ts G31 (mutant in the matrix protein) are still susceptible to T cell-mediated lysis but at a lower level of sensitivity. These results are compatible with the interpretation that for VSV-specific T cell lysis of infected target cells, the viral glycoprotein is a major target antigen and must be expressed, and that the matrix protein plays a lesser role, probably by indirectly influencing glycoprotein configuration at the cell surface."}
{"id": "PMID:210234", "title": "Polymorphonuclear leukocytes as secretory organs of inflammation.", "content": "Polymorphonuclear (PMN) leukocytes mediate that phase of inflammation at which vascular responses become translated into tissue injury. After phagocytosis, the PMN leukocyte generates derivatives of molecular oxygen (O2-.,OH., and H2O2) that stimulate a metabolic burst and assist in the killing of microorganisms. They also release oxidation products of membrane fatty acids (e.g., arachidonate), which are detected as thromboxanes and protaglandins. After interaction of phagocytic ligands (immune complexes and C3b-opsonized particles), the PMN leukocyte secretes lysosomal enzymes from open phagocytic vacuoles, and, especially when phagocytosis is blocked by cytochalasin B, secretes them directly into the cell's surrounding fluids. Secretion is enhanced by agents that elevate intracellular levels of cyclic GMP, and inhibited by agents that raise cyclic AMP. These reciprocal changes are associated with assembly and disassembly (respectively) of cytoplasmic microtubules. These cytoskeletal structures, together with contractile elements, regulate in part the secretory events of inflammation in which lysosomal constituents (e.g., elastase, collagenase, and cathepsin G) are diverted from their intracellular depots to an inappropriate assault on the tissues of the host.", "contents": "Polymorphonuclear leukocytes as secretory organs of inflammation. Polymorphonuclear (PMN) leukocytes mediate that phase of inflammation at which vascular responses become translated into tissue injury. After phagocytosis, the PMN leukocyte generates derivatives of molecular oxygen (O2-.,OH., and H2O2) that stimulate a metabolic burst and assist in the killing of microorganisms. They also release oxidation products of membrane fatty acids (e.g., arachidonate), which are detected as thromboxanes and protaglandins. After interaction of phagocytic ligands (immune complexes and C3b-opsonized particles), the PMN leukocyte secretes lysosomal enzymes from open phagocytic vacuoles, and, especially when phagocytosis is blocked by cytochalasin B, secretes them directly into the cell's surrounding fluids. Secretion is enhanced by agents that elevate intracellular levels of cyclic GMP, and inhibited by agents that raise cyclic AMP. These reciprocal changes are associated with assembly and disassembly (respectively) of cytoplasmic microtubules. These cytoskeletal structures, together with contractile elements, regulate in part the secretory events of inflammation in which lysosomal constituents (e.g., elastase, collagenase, and cathepsin G) are diverted from their intracellular depots to an inappropriate assault on the tissues of the host."}
{"id": "PMID:210235", "title": "Papaverine and Ro 20-1724 inhibit cyclic nucleotide phosphodiesterase activity and increase cyclic AMP levels in psoriatic epidermis in vitro.", "content": "The comparative inhibitory potency of papaverine and Ro 20-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) on cyclic AMP-phosphodiesterase (cAMP-PDE) and cyclic GMP-phosphodiesterase (cGMP-PDE) activities and their effect on the levels of cAMP and cGMP were examined in psoriatic epidermis. At concentrations of 5 X 10(-4) M, papaverine inhibited the hydrolysis of both cAMP and cGMP by either the low or high Km psoriatic epidermal PDE nearly 100% (p less than .0001) while Ro 20-1724 selectively inhibited the hydrolysis of cAMP 94% (p less than .0001) but had no significant effect on cGMP hydrolysis. When keratomed psoriatic epidermal slices were incubated in 5 X 10(-4) M papaverine or Ro 20-1724 the tissue levels of cAMP were increased 343% or 1395% respectively (p less than .001) with no concomitant change in the levels of cGMP. Selective inhibition of cAMP hydrolysis by Ro 20-1724 and its greater effectiveness in elevating cAMP levels in slices of psoriatic epidermis is one explanation for its clinical superiority in treating psoriatic lesions.", "contents": "Papaverine and Ro 20-1724 inhibit cyclic nucleotide phosphodiesterase activity and increase cyclic AMP levels in psoriatic epidermis in vitro. The comparative inhibitory potency of papaverine and Ro 20-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) on cyclic AMP-phosphodiesterase (cAMP-PDE) and cyclic GMP-phosphodiesterase (cGMP-PDE) activities and their effect on the levels of cAMP and cGMP were examined in psoriatic epidermis. At concentrations of 5 X 10(-4) M, papaverine inhibited the hydrolysis of both cAMP and cGMP by either the low or high Km psoriatic epidermal PDE nearly 100% (p less than .0001) while Ro 20-1724 selectively inhibited the hydrolysis of cAMP 94% (p less than .0001) but had no significant effect on cGMP hydrolysis. When keratomed psoriatic epidermal slices were incubated in 5 X 10(-4) M papaverine or Ro 20-1724 the tissue levels of cAMP were increased 343% or 1395% respectively (p less than .001) with no concomitant change in the levels of cGMP. Selective inhibition of cAMP hydrolysis by Ro 20-1724 and its greater effectiveness in elevating cAMP levels in slices of psoriatic epidermis is one explanation for its clinical superiority in treating psoriatic lesions."}
{"id": "PMID:210236", "title": "Comparison of five regimens for treatment of experimental clindamycin-associated colitis.", "content": "The hamster model of clindamycin-induced enterocolitis was studied to determine the natural course of the disease and the response to five therapeutic regimens. Tissue culture assays of stools from untreated animals showed that colitis toxin is present at low titers within 24--36 hr after challenge with clindamycin; titers of toxin in subsequent specimens of stool increased progressively until the animals died on days 2--4 after challenge. Therapeutic regimens tested in this model were initiated 24 hr after clindamycin challenge when the majority of the animals had evidence of colitis toxin. Methylprednisilone, an anion exchange resin, and gas gangrene polyvalent antitoxin had a minimal effect on toxin titers in stool and failed to delay substantially death due to enterocolitis. Vancomycin and tetracycline eliminated toxin in stools and delayed death. However, the salutary effects of these antibiotics were noted only during the course of their administration since all animals died of enterocolitis and had high titers of toxin when treatment was discontinued.", "contents": "Comparison of five regimens for treatment of experimental clindamycin-associated colitis. The hamster model of clindamycin-induced enterocolitis was studied to determine the natural course of the disease and the response to five therapeutic regimens. Tissue culture assays of stools from untreated animals showed that colitis toxin is present at low titers within 24--36 hr after challenge with clindamycin; titers of toxin in subsequent specimens of stool increased progressively until the animals died on days 2--4 after challenge. Therapeutic regimens tested in this model were initiated 24 hr after clindamycin challenge when the majority of the animals had evidence of colitis toxin. Methylprednisilone, an anion exchange resin, and gas gangrene polyvalent antitoxin had a minimal effect on toxin titers in stool and failed to delay substantially death due to enterocolitis. Vancomycin and tetracycline eliminated toxin in stools and delayed death. However, the salutary effects of these antibiotics were noted only during the course of their administration since all animals died of enterocolitis and had high titers of toxin when treatment was discontinued."}
{"id": "PMID:210237", "title": "Inactivation of cytomegalovirus and Semliki Forest virus by butylated hydroxytoluene.", "content": "Butylated hydroxytoluene (BHT) is an antioxidant that is widely used in foods because it prevents spoilage by delaying degradation of lipid components. This hydrophobic compound inactivated human and murine cytomegalovirus (CMV) and Semliki Forest virus (SFV). Both human and murine CMV were inactivated more than 90% by 40 microgram of BHT/ml after incubation for 1 hr at 37 C. Under the same conditions, SVF was inactivated about 75%, whereas poliovirus, which does not contain lipid membrane as a part of its structure, was not inactivated at all. Vaccinia virus was less sensitive to BHT than was CMV or SFV.", "contents": "Inactivation of cytomegalovirus and Semliki Forest virus by butylated hydroxytoluene. Butylated hydroxytoluene (BHT) is an antioxidant that is widely used in foods because it prevents spoilage by delaying degradation of lipid components. This hydrophobic compound inactivated human and murine cytomegalovirus (CMV) and Semliki Forest virus (SFV). Both human and murine CMV were inactivated more than 90% by 40 microgram of BHT/ml after incubation for 1 hr at 37 C. Under the same conditions, SVF was inactivated about 75%, whereas poliovirus, which does not contain lipid membrane as a part of its structure, was not inactivated at all. Vaccinia virus was less sensitive to BHT than was CMV or SFV."}
{"id": "PMID:210238", "title": "Cytomegalovirus infection in guinea pigs. I. Viremia during acute primary and chronic persistent infection.", "content": "Studies on the pathogenesis of cytomegalovirus (CMV) infection in guinea pigs have revealed two distinct phases of infection, without any signs of clinical disease. During acute primary infection, viremia was easily demonstrated and infectious virus was recovered from various tissues, including lung, spleen, and kidney, of the infected animal two to 10 days after inoculation. Chronic persistent infection was readily established thereafter. In animals with chronic persistent infection with high levels of circulating antibody, infectious virus was consistently isolated from the salivary gland and pancreas. Evidence of CMV in the blood of the persistently infected animals was detected only occasionally and only when a highly sensitive method and/or a large inoculum was used. However, the anticoagulant heparin was found to inactivate CMV significantly during collection of blood. These data suggest that CMV was indeed circulating in the blood of apparently health but persistently infected animals for prolonged periods. Such infected blood could conceivably be the source of CMV infection when large quantities of blood are given to susceptible recipients.", "contents": "Cytomegalovirus infection in guinea pigs. I. Viremia during acute primary and chronic persistent infection. Studies on the pathogenesis of cytomegalovirus (CMV) infection in guinea pigs have revealed two distinct phases of infection, without any signs of clinical disease. During acute primary infection, viremia was easily demonstrated and infectious virus was recovered from various tissues, including lung, spleen, and kidney, of the infected animal two to 10 days after inoculation. Chronic persistent infection was readily established thereafter. In animals with chronic persistent infection with high levels of circulating antibody, infectious virus was consistently isolated from the salivary gland and pancreas. Evidence of CMV in the blood of the persistently infected animals was detected only occasionally and only when a highly sensitive method and/or a large inoculum was used. However, the anticoagulant heparin was found to inactivate CMV significantly during collection of blood. These data suggest that CMV was indeed circulating in the blood of apparently health but persistently infected animals for prolonged periods. Such infected blood could conceivably be the source of CMV infection when large quantities of blood are given to susceptible recipients."}
{"id": "PMID:210239", "title": "Cytomegalovirus infection in guinea pigs. II. Transplacental and horizontal transmission.", "content": "Transplacental transmission of cytomegalovirus (CMV) was demonstrated in guinea pigs, but transmission only occurred during acute primary maternal infection. Infectious CMV was isolated from 27 of 44 placental tissues and nine of 37 fetal tissues (including brain, lung, and kidney) tested five to 24 days after maternal infection. Fetal infection occurred at different stages of gestation ranging from 28 to 60 days. No virus was detected in the tissues of 43 fetuses examined that were taken from pregnant guinea pigs that had been infected for greater than 30 days. The maternal animals had significant levels of circulating neutralizing antibody concurrent with infectious CMV in the salivary glands at the time of sacrifice. Contact infection was accomplished when infected and uninfected animals of either the same sex or oppsite sexes were paired and housed together for one to three months. Among the seven male contact guinea pigs housed with infected females, five showed virus in their salivary glands, and all seven showed rises in titer of antibody; five of the females became pregnant. In contrast, when infected and uninfected animals of the same sex were paired and housed together, only one of 13 contact animals had virus in the salivary gland, and four of 13 had rises in titer of antibody. Thus sexual contact appeared to be more efficient than environmental contact in the spread of CMV infection.", "contents": "Cytomegalovirus infection in guinea pigs. II. Transplacental and horizontal transmission. Transplacental transmission of cytomegalovirus (CMV) was demonstrated in guinea pigs, but transmission only occurred during acute primary maternal infection. Infectious CMV was isolated from 27 of 44 placental tissues and nine of 37 fetal tissues (including brain, lung, and kidney) tested five to 24 days after maternal infection. Fetal infection occurred at different stages of gestation ranging from 28 to 60 days. No virus was detected in the tissues of 43 fetuses examined that were taken from pregnant guinea pigs that had been infected for greater than 30 days. The maternal animals had significant levels of circulating neutralizing antibody concurrent with infectious CMV in the salivary glands at the time of sacrifice. Contact infection was accomplished when infected and uninfected animals of either the same sex or oppsite sexes were paired and housed together for one to three months. Among the seven male contact guinea pigs housed with infected females, five showed virus in their salivary glands, and all seven showed rises in titer of antibody; five of the females became pregnant. In contrast, when infected and uninfected animals of the same sex were paired and housed together, only one of 13 contact animals had virus in the salivary gland, and four of 13 had rises in titer of antibody. Thus sexual contact appeared to be more efficient than environmental contact in the spread of CMV infection."}
{"id": "PMID:210240", "title": "Effects of gentamicin on trypsin, chymotrypsin, and collagenase.", "content": "The effects of gentamicin on three proteolytic enzymes were studied. Gentamicin was tested at concentrations of 0.5-500 microgram/ml. Trypsin was tested at 0.5 microgram/ml using p-tosyl-L-arginine methyl ester and at 0.1 and 0.5 microgram/ml using azocoll as the substrate. Chymotrypsin was tested at 0.1 and 0.5 microgram/ml with azocoll. A soluble [14C]collagen assay was used to measure activity of collagenase derived from Clostridium histolyticum. The profiles of proteolytic activity vs. gentamicin concentration were similar for all three enzymes. At lower concentrations of gentamicin (less than 70 microgram/ml), there were two peaks of enhanced protease activity generally followed by inhibition. These unusual multiphasic effects of gentamicin on three different proteases are not presently understood, but they imply a previously unreported mode of action for this antibiotic.", "contents": "Effects of gentamicin on trypsin, chymotrypsin, and collagenase. The effects of gentamicin on three proteolytic enzymes were studied. Gentamicin was tested at concentrations of 0.5-500 microgram/ml. Trypsin was tested at 0.5 microgram/ml using p-tosyl-L-arginine methyl ester and at 0.1 and 0.5 microgram/ml using azocoll as the substrate. Chymotrypsin was tested at 0.1 and 0.5 microgram/ml with azocoll. A soluble [14C]collagen assay was used to measure activity of collagenase derived from Clostridium histolyticum. The profiles of proteolytic activity vs. gentamicin concentration were similar for all three enzymes. At lower concentrations of gentamicin (less than 70 microgram/ml), there were two peaks of enhanced protease activity generally followed by inhibition. These unusual multiphasic effects of gentamicin on three different proteases are not presently understood, but they imply a previously unreported mode of action for this antibiotic."}
{"id": "PMID:210244", "title": "Nasopharyngeal angiofibroma.", "content": "Three cases of nasopharyngeal angiofibroma have been described along with the histopathological findings, treatment and a brief review of the literature on the subject. It is of interest that one of these cases, histologically proven, was a female and this in spite of some rigidly held views about the strict sex linkage of the lesion. The tumour is uncommon but it is possible that unfamiliarity with the histopathology, as well as the likelihood of cessation of activity at any stage, may in part be responsible for its low recorded prevalence. The progress of each patient after four, two and one year respectively gives cause for some optimism, but the long-term prognosis must remain guarded.", "contents": "Nasopharyngeal angiofibroma. Three cases of nasopharyngeal angiofibroma have been described along with the histopathological findings, treatment and a brief review of the literature on the subject. It is of interest that one of these cases, histologically proven, was a female and this in spite of some rigidly held views about the strict sex linkage of the lesion. The tumour is uncommon but it is possible that unfamiliarity with the histopathology, as well as the likelihood of cessation of activity at any stage, may in part be responsible for its low recorded prevalence. The progress of each patient after four, two and one year respectively gives cause for some optimism, but the long-term prognosis must remain guarded."}
{"id": "PMID:210246", "title": "Solubilization and partial characterization of human and porcine thyrotrophin receptors.", "content": "Thyrotrophin (TSH) receptors have been extracted from human and porcine thyroid membranes by treatment with Triton X-100. 125I-Labelled bovine TSH was used to monitor receptor activity. Analysis by gel filtration and electrophoresis on acrylamide gels containing sodium dodecyl sulphate suggested that Triton extracts of human thyroid membranes contained TSH receptors with a molecular weight in the region of 50 000 closely associated with Triton micelles of approximate molecular weight 300 000. Isoelectric focusing studies indicated that the Triton-solubilized TSH binding activity had an isoelectric point of pH 4--4.5. The soluble TSH receptors were heat-labile, showed optimum TSH binding at pH 7.4 and reduced hormone binding at high ionic strength. The TSH binding characteristics of membrane-bound and solubilized human TSH receptors were similar and both preparations gave curved Scatchard plots. Solublized porcine TSH receptors appeared to have a similar molecular weight to the human receptors and were also closely associated with Triton micelles of approximate molecular weight 300 000. Scatchard analysis of TSH binding to membrane-bound or solubilized porcine TSH receptors gave approximately linear plots with association constants of 2.8 +/- 0.95 (S.E.M.) X 10(9) and 1.7 +/- 0.27 x 10(9) l/mol respectively. Comparison of the binding capacities of the solubilized and membrane-bound porcine receptors indicated that the 0.5% Triton extracts contained 40% of the original TSH binding activity and that this was present at a concentration of 25 ng/ml.", "contents": "Solubilization and partial characterization of human and porcine thyrotrophin receptors. Thyrotrophin (TSH) receptors have been extracted from human and porcine thyroid membranes by treatment with Triton X-100. 125I-Labelled bovine TSH was used to monitor receptor activity. Analysis by gel filtration and electrophoresis on acrylamide gels containing sodium dodecyl sulphate suggested that Triton extracts of human thyroid membranes contained TSH receptors with a molecular weight in the region of 50 000 closely associated with Triton micelles of approximate molecular weight 300 000. Isoelectric focusing studies indicated that the Triton-solubilized TSH binding activity had an isoelectric point of pH 4--4.5. The soluble TSH receptors were heat-labile, showed optimum TSH binding at pH 7.4 and reduced hormone binding at high ionic strength. The TSH binding characteristics of membrane-bound and solubilized human TSH receptors were similar and both preparations gave curved Scatchard plots. Solublized porcine TSH receptors appeared to have a similar molecular weight to the human receptors and were also closely associated with Triton micelles of approximate molecular weight 300 000. Scatchard analysis of TSH binding to membrane-bound or solubilized porcine TSH receptors gave approximately linear plots with association constants of 2.8 +/- 0.95 (S.E.M.) X 10(9) and 1.7 +/- 0.27 x 10(9) l/mol respectively. Comparison of the binding capacities of the solubilized and membrane-bound porcine receptors indicated that the 0.5% Triton extracts contained 40% of the original TSH binding activity and that this was present at a concentration of 25 ng/ml."}
{"id": "PMID:210247", "title": "Isolation of a heterogeneous population of temperature-sensitive mutants of measles virus from persistently infected human lymphoblastoid cell lines.", "content": "Two human lymphoblastoid B-cell lines, WI-L2 and 8866, were infected with the Edmonston strain of measles virus at a multiplicity of infection of 10(-6), and stable persistent infections were established. By immunofluorescence and electron microscopy, the vast majority of cells from both cell lines were expressing viral antigens and releasing virion-like particles. However, very little infectious virus could be detected at 37 degrees C, either by an infectious centers assay or by titration of supernates from persistently infected cultures. When cultures were shifted to 31 degrees C, the cells released a population of virus that was temperature-sensitive. Clonal analysis of supernatant virus at 31 degrees C revealed a highly heterogeneous population of temperature-sensitive mutants, differing in plating efficiency ratios, thermolability, and antigen production at the nonpermissive temperature. Factors such as interferon, defective interfering particles, and extracellular virus do not appear to be important in maintaining the persistent carrier state. These studies have important implications for persistent infections of lymphoid cells in vivo, and the slow neurological diseases associated with measles, subacute sclerosing panencephalitis, and multiple sclerosis.", "contents": "Isolation of a heterogeneous population of temperature-sensitive mutants of measles virus from persistently infected human lymphoblastoid cell lines. Two human lymphoblastoid B-cell lines, WI-L2 and 8866, were infected with the Edmonston strain of measles virus at a multiplicity of infection of 10(-6), and stable persistent infections were established. By immunofluorescence and electron microscopy, the vast majority of cells from both cell lines were expressing viral antigens and releasing virion-like particles. However, very little infectious virus could be detected at 37 degrees C, either by an infectious centers assay or by titration of supernates from persistently infected cultures. When cultures were shifted to 31 degrees C, the cells released a population of virus that was temperature-sensitive. Clonal analysis of supernatant virus at 31 degrees C revealed a highly heterogeneous population of temperature-sensitive mutants, differing in plating efficiency ratios, thermolability, and antigen production at the nonpermissive temperature. Factors such as interferon, defective interfering particles, and extracellular virus do not appear to be important in maintaining the persistent carrier state. These studies have important implications for persistent infections of lymphoid cells in vivo, and the slow neurological diseases associated with measles, subacute sclerosing panencephalitis, and multiple sclerosis."}
{"id": "PMID:210248", "title": "Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions.", "content": "The effects of glucocorticoids on biochemical functions of macrophages from man, mouse, rabbit, and guinea pig were examined. Secretion of plasminogen activator by human peripheral blood monocytes was decreased by 50% with 1 nM dexamethasone. Differentiation of murine monocytic and granulocytic colonies in agar from bone marrow precursors was decreased by 50% at 7 days with 20 nM dexamethasone. Secretion of elastase, collagenase, and plasminogen activator by resident and thioglycollate-elicited mouse peritoneal macrophages was decreased by dexamethasone, cortisol, and triamcinolone acetonide (1--1,000 nM), but not by progesterone, estradiol, and dihydrotestosterone (1,000 nM); in contrast, secretion of lysozyme was not affected by glucocorticoids or other steroids. The inhibition of macrophage secretion by dexamethasone was both time and dose dependent. Effects were detected within 1--6 h after addition of the glucocorticoids, became maximum by 24 h, and were reversed during a similar time period after removal of the hormones. The extent of inhibition of macrophage secretion increased with increasing glucocorticoid concentration. Half-maximum inhibition of secretion of elastase, collagenase, and plasminogen activator was seen at dexamethasone concentrations (1--10 nM) similar to those that half-saturated the specific glucocorticoid receptors in these cells. At high concentrations of dexamethasone (100--1,000 nM) the secretion of plasminogen activator was inhibited to a greater extent (greater than 95%) than the secretion of elastase (60--80%). Progesterone alone had no effect on secretion, but it blocked the inhibitory effects of dexamethasone and cortisol. Secretion of collagenase, neutral proteinases, and plasminogen activator by elicited rabbit alveolar macrophages was inhibited with glucocorticoids (0.1--100 nM) but not with progesterone or sex steroids. Secretion of a neutral elastinolytic proteinase by guinea pig alveolar macrophages was also inhibited by dexamethasone. These data support the regulatory role of glucocorticoids on macrophage functions at physiological concentrations.", "contents": "Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions. The effects of glucocorticoids on biochemical functions of macrophages from man, mouse, rabbit, and guinea pig were examined. Secretion of plasminogen activator by human peripheral blood monocytes was decreased by 50% with 1 nM dexamethasone. Differentiation of murine monocytic and granulocytic colonies in agar from bone marrow precursors was decreased by 50% at 7 days with 20 nM dexamethasone. Secretion of elastase, collagenase, and plasminogen activator by resident and thioglycollate-elicited mouse peritoneal macrophages was decreased by dexamethasone, cortisol, and triamcinolone acetonide (1--1,000 nM), but not by progesterone, estradiol, and dihydrotestosterone (1,000 nM); in contrast, secretion of lysozyme was not affected by glucocorticoids or other steroids. The inhibition of macrophage secretion by dexamethasone was both time and dose dependent. Effects were detected within 1--6 h after addition of the glucocorticoids, became maximum by 24 h, and were reversed during a similar time period after removal of the hormones. The extent of inhibition of macrophage secretion increased with increasing glucocorticoid concentration. Half-maximum inhibition of secretion of elastase, collagenase, and plasminogen activator was seen at dexamethasone concentrations (1--10 nM) similar to those that half-saturated the specific glucocorticoid receptors in these cells. At high concentrations of dexamethasone (100--1,000 nM) the secretion of plasminogen activator was inhibited to a greater extent (greater than 95%) than the secretion of elastase (60--80%). Progesterone alone had no effect on secretion, but it blocked the inhibitory effects of dexamethasone and cortisol. Secretion of collagenase, neutral proteinases, and plasminogen activator by elicited rabbit alveolar macrophages was inhibited with glucocorticoids (0.1--100 nM) but not with progesterone or sex steroids. Secretion of a neutral elastinolytic proteinase by guinea pig alveolar macrophages was also inhibited by dexamethasone. These data support the regulatory role of glucocorticoids on macrophage functions at physiological concentrations."}
{"id": "PMID:210249", "title": "The generation and regulation of lymphocyte populations: evidence from differentiative induction systems in vitro.", "content": "Results with a dual assay, for the induction of Thy-1+ T cells and of CR+ B cells from marker-negative precursors, confirm that thymopoietin is at present the only known selective inducer of prothymocytes. In contrast, various inducers, including ubiquitin, are active in both assays. Pharmacological evidence indicates that there are different cellular receptors for ubiquitin and thymopoietin. Prothymocytes and pro-CR+ B cells compose two distinct populations in bone marrow and spleen; their distribution in density gradients is different, and elimination of either population enriches the other proportionately. There are no noteworthy differences between induction of these two populations in regard to (a) kinetics, (b) dependence on temperature and protein synthesis, (c) activation by cAMP, and (d) inhibition by cGMP. The opposite inductive effects of cAMP and cGMP were corroborated by the use of pharmacological agents that raise or lower the levels of intracellular cyclic nucleotides. In contrast, a third induction assay, which monitors acquisition of the PC+ surface phenotype, indicates that this differentiative step, the last known for B cells, is initiated by cGMP and inhibited by cAMP. Induction of PC is also inhibited by thymopoietin, signifying that the inductive selectivity of thymopoietin is not due to restriction of its receptors to the T lineage cells. Rather it seems that receptors for thymopoietin occur also on PC-inducible and other B cells, although in this case geared biochemically to inhibition rather than expression of the succeeding gene program. This suggests a role for thymopoietin in the coordinated interregulation of lymphocyte classes, in addition to its better-known function as the thymic inducer of prothymocytes. Present data conform to a general scheme in which the cyclic nucleotides cAMP and cGMP, and agents that affect intracellular levels of these mediators, influence reciprocally the early and late (functional) phases of lymphocyte differentiation as a whole, while thymopoietin influences reciprocally the differentiation of the B and T classes of lymphocyte.", "contents": "The generation and regulation of lymphocyte populations: evidence from differentiative induction systems in vitro. Results with a dual assay, for the induction of Thy-1+ T cells and of CR+ B cells from marker-negative precursors, confirm that thymopoietin is at present the only known selective inducer of prothymocytes. In contrast, various inducers, including ubiquitin, are active in both assays. Pharmacological evidence indicates that there are different cellular receptors for ubiquitin and thymopoietin. Prothymocytes and pro-CR+ B cells compose two distinct populations in bone marrow and spleen; their distribution in density gradients is different, and elimination of either population enriches the other proportionately. There are no noteworthy differences between induction of these two populations in regard to (a) kinetics, (b) dependence on temperature and protein synthesis, (c) activation by cAMP, and (d) inhibition by cGMP. The opposite inductive effects of cAMP and cGMP were corroborated by the use of pharmacological agents that raise or lower the levels of intracellular cyclic nucleotides. In contrast, a third induction assay, which monitors acquisition of the PC+ surface phenotype, indicates that this differentiative step, the last known for B cells, is initiated by cGMP and inhibited by cAMP. Induction of PC is also inhibited by thymopoietin, signifying that the inductive selectivity of thymopoietin is not due to restriction of its receptors to the T lineage cells. Rather it seems that receptors for thymopoietin occur also on PC-inducible and other B cells, although in this case geared biochemically to inhibition rather than expression of the succeeding gene program. This suggests a role for thymopoietin in the coordinated interregulation of lymphocyte classes, in addition to its better-known function as the thymic inducer of prothymocytes. Present data conform to a general scheme in which the cyclic nucleotides cAMP and cGMP, and agents that affect intracellular levels of these mediators, influence reciprocally the early and late (functional) phases of lymphocyte differentiation as a whole, while thymopoietin influences reciprocally the differentiation of the B and T classes of lymphocyte."}
{"id": "PMID:210250", "title": "Tampon culture for quantitation of cervicovaginal herpes simplex virus.", "content": "From 10(1) to 10(6) TCID50 (mean tissue culture infective doses) per ml HSV I and II can be quantitatively recorded from vaginal tampons. Tampons and sterile cotton swabs are equally sensitive in recovering HSV I and II. Direct cotton swab cultures of the cervix and cervicovaginal tampon cultures from the same patients recovered similar quantities of HSV, ranging from 1.5 to 6.5 log10 TCID50/ml in 5 patients.", "contents": "Tampon culture for quantitation of cervicovaginal herpes simplex virus. From 10(1) to 10(6) TCID50 (mean tissue culture infective doses) per ml HSV I and II can be quantitatively recorded from vaginal tampons. Tampons and sterile cotton swabs are equally sensitive in recovering HSV I and II. Direct cotton swab cultures of the cervix and cervicovaginal tampon cultures from the same patients recovered similar quantities of HSV, ranging from 1.5 to 6.5 log10 TCID50/ml in 5 patients."}
{"id": "PMID:210251", "title": "Rotavirus infections in adults in association with acute gastroenteritis.", "content": "During an epidemic of acute gastroenteritis in Helsinki, in March--May 1976, 18 out of 40 adult patients showed electron microscopic and/or serologic evidence for rotavirus infection. Rotavirus was most frequently seen in the fecal suspensions from 2 to 6 days after the onset of the symptoms but persisted in one patient for as long as 10 days. An increase in the complement-fixing (CF) serum antibody titers against the related Nebraska calf diarrhea virus (NCDV), or an initially high titer and subsequent significant decrease, was seen in all but one patient with rotavirus-positive feces, and in 6 additional patients. This suggests that using electron microscopy as the only diagnostic procedure a considerable number of rotavirus infections in adults remain undetected. Immune response against autologous or homologous rotavirus was also documented by immunoelectron microscopy. Complement-fixing antibody titers against NCDV decreased significantly from the convalescence values over a half-year observation period, but still remained clearly above the titers of a gastroenteritis-negative control population.", "contents": "Rotavirus infections in adults in association with acute gastroenteritis. During an epidemic of acute gastroenteritis in Helsinki, in March--May 1976, 18 out of 40 adult patients showed electron microscopic and/or serologic evidence for rotavirus infection. Rotavirus was most frequently seen in the fecal suspensions from 2 to 6 days after the onset of the symptoms but persisted in one patient for as long as 10 days. An increase in the complement-fixing (CF) serum antibody titers against the related Nebraska calf diarrhea virus (NCDV), or an initially high titer and subsequent significant decrease, was seen in all but one patient with rotavirus-positive feces, and in 6 additional patients. This suggests that using electron microscopy as the only diagnostic procedure a considerable number of rotavirus infections in adults remain undetected. Immune response against autologous or homologous rotavirus was also documented by immunoelectron microscopy. Complement-fixing antibody titers against NCDV decreased significantly from the convalescence values over a half-year observation period, but still remained clearly above the titers of a gastroenteritis-negative control population."}
{"id": "PMID:210252", "title": "A nonlytic transforming mutant of herpes simplex virus type 2.", "content": "A small-plaque mutant (NO.69) of herpes simplex virus type 2 (HSV-2) strain 333 has been previously isolated and characterized in this laboratory. This mutant was shown to produce a high ratio of noninfectious to infectious particles when grown at the nonpermissive temperature in hamster embryo fibroblasts [Westmoreland D. and Rapp F. (1976). Journal of Virology [8:92--102]. In this study, we have demonstrated that it is possible to obtain noninfectious stocks of this virus which retain transforming ability in a biochemical transformation assay specific for detection of the HSV gene for thymidine kinase. This mutant contains a DNA genome that has a density identical to the DNA of wild-type virus. Virus and cell DNA synthesis after infection with the mutant at both the permissive and nonpermissive temperature are similar to that observed in cultures infected with the parental virus. Clones of mouse cells biochemically transformed by this virus contain HSV antigens and are presently being examined for oncogenicity.", "contents": "A nonlytic transforming mutant of herpes simplex virus type 2. A small-plaque mutant (NO.69) of herpes simplex virus type 2 (HSV-2) strain 333 has been previously isolated and characterized in this laboratory. This mutant was shown to produce a high ratio of noninfectious to infectious particles when grown at the nonpermissive temperature in hamster embryo fibroblasts [Westmoreland D. and Rapp F. (1976). Journal of Virology [8:92--102]. In this study, we have demonstrated that it is possible to obtain noninfectious stocks of this virus which retain transforming ability in a biochemical transformation assay specific for detection of the HSV gene for thymidine kinase. This mutant contains a DNA genome that has a density identical to the DNA of wild-type virus. Virus and cell DNA synthesis after infection with the mutant at both the permissive and nonpermissive temperature are similar to that observed in cultures infected with the parental virus. Clones of mouse cells biochemically transformed by this virus contain HSV antigens and are presently being examined for oncogenicity."}
{"id": "PMID:210253", "title": "Cytomegalovirus proteins: II. Polypeptide composition of cytomegalovirus complement-fixing antigen.", "content": "Complement-fixing (CF) antigen, prepared from cytomegalovirus (CMV)-infected cells and solubilized by urea and Tween-20, was fractionated on agarose gel columns. Its molecular weight was 1.5--5 X 10(7) daltons, and it contained 5 major peptides with molecular weights from 60,000--90,000 daltons. The peptide with a molecular weight of 70,000 daltons which was present in the solubilized CF antigen was absent in a soluble fraction from infected cells without CF activity and may be, therefore, important in this respect. The antigens present in the CF antigen did not elicit neutralizing antibody.", "contents": "Cytomegalovirus proteins: II. Polypeptide composition of cytomegalovirus complement-fixing antigen. Complement-fixing (CF) antigen, prepared from cytomegalovirus (CMV)-infected cells and solubilized by urea and Tween-20, was fractionated on agarose gel columns. Its molecular weight was 1.5--5 X 10(7) daltons, and it contained 5 major peptides with molecular weights from 60,000--90,000 daltons. The peptide with a molecular weight of 70,000 daltons which was present in the solubilized CF antigen was absent in a soluble fraction from infected cells without CF activity and may be, therefore, important in this respect. The antigens present in the CF antigen did not elicit neutralizing antibody."}
{"id": "PMID:210254", "title": "Experimental respiratory syncytial virus pneumonia in cebus monkeys.", "content": "Into 14 juvenile cebus monkeys that lacked serum antibodies for RS virus 10(8) plaque-forming units (pfu) of wild-type respiratory syncytial (RS) virus were inoculated transtracheally. Roentgenographic evidence of pneumonia developed in 13 of 14 infected animals. Gross pathologic changes occurred in each of the 13 monkeys that were sacrificed. Patchy areas of red consolidation were seen in the lower lobes 24 hours after inoculation, and there was progression to gray consolidation seven days later. Each of the infected animals had histologic evidence of interstitial pneumonia. Changes were detected in the lung as early as 24 hours after inoculation; they consisted primarily of infiltration of the alveolar wall. By the fourth to sixth day after inoculation there was marked interstitial thickening, pulmonary consolidation, formation of multinucleated giant cells and development of eosinophilic cytoplasmic inclusion bodies within alveolar cells. RS viral antigens, detected by indirect immunofluorescence, were distributed throughout cells of the alveolar wall and the bronchiolar epithelium. The virus grew to highest titer in the lungs on the fourth to sixth day after inoculation; up to 10(8) pfu/gram of tissue were detected. The cebus monkey represents the first experimental host to develop extensive pulmonary lesions during infection with respiratory syncytial virus.", "contents": "Experimental respiratory syncytial virus pneumonia in cebus monkeys. Into 14 juvenile cebus monkeys that lacked serum antibodies for RS virus 10(8) plaque-forming units (pfu) of wild-type respiratory syncytial (RS) virus were inoculated transtracheally. Roentgenographic evidence of pneumonia developed in 13 of 14 infected animals. Gross pathologic changes occurred in each of the 13 monkeys that were sacrificed. Patchy areas of red consolidation were seen in the lower lobes 24 hours after inoculation, and there was progression to gray consolidation seven days later. Each of the infected animals had histologic evidence of interstitial pneumonia. Changes were detected in the lung as early as 24 hours after inoculation; they consisted primarily of infiltration of the alveolar wall. By the fourth to sixth day after inoculation there was marked interstitial thickening, pulmonary consolidation, formation of multinucleated giant cells and development of eosinophilic cytoplasmic inclusion bodies within alveolar cells. RS viral antigens, detected by indirect immunofluorescence, were distributed throughout cells of the alveolar wall and the bronchiolar epithelium. The virus grew to highest titer in the lungs on the fourth to sixth day after inoculation; up to 10(8) pfu/gram of tissue were detected. The cebus monkey represents the first experimental host to develop extensive pulmonary lesions during infection with respiratory syncytial virus."}
{"id": "PMID:210255", "title": "Brain reaggregate cultures: biochemical evidence for myelin membrane synthesis.", "content": "Myelin membrane synthesis was studied using mechanically dissociated fetal rodent CNS which formed spherical reaggregates while being maintained in rotating culture flasks. These reaggregate cultures exhibited myelinogenesis in vitro after precisely the same period of time needed for myelin synthesis to commence in vivo. The myelin membrane related enzymes, 2', 3' cyclic nucleotide phosphohydrolase (CNP) and cerebroside sulfotransferase (CST), appear similar in their specific activities and follow the same developmental patterns that these enzymes exhibit in vivo. In addition, phosphorylation of myelin basic protein occurs by the third week in vitro which agrees with previously published in vivo studies. These experiments indicate that this nerve-cell culture system may be a appropriate model for studying the biological regulation of myelinogenesis as well as a variety of other nervous-system functions.", "contents": "Brain reaggregate cultures: biochemical evidence for myelin membrane synthesis. Myelin membrane synthesis was studied using mechanically dissociated fetal rodent CNS which formed spherical reaggregates while being maintained in rotating culture flasks. These reaggregate cultures exhibited myelinogenesis in vitro after precisely the same period of time needed for myelin synthesis to commence in vivo. The myelin membrane related enzymes, 2', 3' cyclic nucleotide phosphohydrolase (CNP) and cerebroside sulfotransferase (CST), appear similar in their specific activities and follow the same developmental patterns that these enzymes exhibit in vivo. In addition, phosphorylation of myelin basic protein occurs by the third week in vitro which agrees with previously published in vivo studies. These experiments indicate that this nerve-cell culture system may be a appropriate model for studying the biological regulation of myelinogenesis as well as a variety of other nervous-system functions."}
{"id": "PMID:210262", "title": "Intracranial space-occupying masses in mental hospital patients: necropsy study.", "content": "During a three year period 1970--1973 necropsies were performed on 200 patients who died in a mental hospital in the Transvaal, South Africa. There was no selection of cases other than availability of consent for postmortem examination. The necropsy rate for this period was 56%. The patients belonged to three racial groups, Black, White, and Coloured, the latter being defined as those of mixed blood. Among these 200 cases, 27 were found at necropsy to have an intracranial space-occupying mass. Mention is made of the literature dealing with the incidence and diagnosis of intracranial space-occupying masses in mental hospital patients, and the incidence of intracranial space-occupying masses in the different racial groups in South Africa.", "contents": "Intracranial space-occupying masses in mental hospital patients: necropsy study. During a three year period 1970--1973 necropsies were performed on 200 patients who died in a mental hospital in the Transvaal, South Africa. There was no selection of cases other than availability of consent for postmortem examination. The necropsy rate for this period was 56%. The patients belonged to three racial groups, Black, White, and Coloured, the latter being defined as those of mixed blood. Among these 200 cases, 27 were found at necropsy to have an intracranial space-occupying mass. Mention is made of the literature dealing with the incidence and diagnosis of intracranial space-occupying masses in mental hospital patients, and the incidence of intracranial space-occupying masses in the different racial groups in South Africa."}
{"id": "PMID:210263", "title": "Myasthenia gravis: further electrophysiological and ultrastructural analysis of transmission failure in the mouse passive transfer model.", "content": "Using the mouse passive transfer model the mean amplitude of miniature endplate potentials and endplate potentials of mice treated with myasthenic immunoglobulins was markedly decreased. Miniature endplate potential frequency and quantum content of endplate potentials were normal, arguing against a major presynaptic disarrangement. Under electron-microscopy no gross structural alterations of endplates were demonstrated. It is concluded that the mouse passive transfer model closely resembles human myasthenia gravis of recent onset.", "contents": "Myasthenia gravis: further electrophysiological and ultrastructural analysis of transmission failure in the mouse passive transfer model. Using the mouse passive transfer model the mean amplitude of miniature endplate potentials and endplate potentials of mice treated with myasthenic immunoglobulins was markedly decreased. Miniature endplate potential frequency and quantum content of endplate potentials were normal, arguing against a major presynaptic disarrangement. Under electron-microscopy no gross structural alterations of endplates were demonstrated. It is concluded that the mouse passive transfer model closely resembles human myasthenia gravis of recent onset."}
{"id": "PMID:210264", "title": "Synaptic transmission without action potentials: input-output properties of a nonspiking presynaptic neuron.", "content": "1. Input-output properties of the inhibitory synaptic connection between non-spiking neurons (EX1) and gastric mill (GM) neurons were examined in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. Current was injected into and the voltage was recorded during current injection, two independent microelectrodes were used. 2. The EX1-GM synaptic connection is a conductance-increase inhibitory type, with an input-output curve that resembles the curve for the squid giant synapse. There is a threshold level of depolarization for transmitter release from the presynaptic cell. Beyond that threshold, increasing presynaptic depolarization causes increasing postsynaptic hyperpolarization (and inhibition). 3. A long presynaptic current step always causes a postsynaptic response with an initial peak of hyperpolarization followed by a decay to a less hyperpolarized plateau level. The plateau level is maintained, in most cells, for the duration of the presynaptic depolarization even over long periods (30 s). 4. The peak, but not the plateau, part of the postsynaptic response is sensitive to the past history of the synaptic connection. If a large conditioning pulse is applied to the presynaptic cell causing a large postsynaptic hyperpolarization, then the postsynaptic response to a later presynaptic test depolarization will have a reduced peak, leaving the plateau component unchanged.", "contents": "Synaptic transmission without action potentials: input-output properties of a nonspiking presynaptic neuron. 1. Input-output properties of the inhibitory synaptic connection between non-spiking neurons (EX1) and gastric mill (GM) neurons were examined in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. Current was injected into and the voltage was recorded during current injection, two independent microelectrodes were used. 2. The EX1-GM synaptic connection is a conductance-increase inhibitory type, with an input-output curve that resembles the curve for the squid giant synapse. There is a threshold level of depolarization for transmitter release from the presynaptic cell. Beyond that threshold, increasing presynaptic depolarization causes increasing postsynaptic hyperpolarization (and inhibition). 3. A long presynaptic current step always causes a postsynaptic response with an initial peak of hyperpolarization followed by a decay to a less hyperpolarized plateau level. The plateau level is maintained, in most cells, for the duration of the presynaptic depolarization even over long periods (30 s). 4. The peak, but not the plateau, part of the postsynaptic response is sensitive to the past history of the synaptic connection. If a large conditioning pulse is applied to the presynaptic cell causing a large postsynaptic hyperpolarization, then the postsynaptic response to a later presynaptic test depolarization will have a reduced peak, leaving the plateau component unchanged."}
{"id": "PMID:210266", "title": "Skeletal uptake of pyrophosphate labeled with technetium-95m and technetium-96, as evaluated by autoradiography.", "content": "For animal experimentation, the 95m and 96 technetium isotopes offer many advantages over technetium-99m. Their long physical half-lives and the emission of extranuclear electrons of low penetrating power make it possible to obtain autoradiograms of a great precision. The uptake of technetium stannous pyrophosphate by the epiphyseal plate was studied using liquid-emulsion microautoradiography, 3 hr after i.v. injection into 10-week-old rabbits. Microautoradiograms showed a well-defined and rather specific pattern of localization with intense uptake beneath the epiphyseal disk on the extremities of the vascular buds and a lack of accumulation in the cartilage, whether calcified or uncalcified. In the metaphysis, the label was located where new bone was being laid down and also over the cytoplasm of osteoclasts. We deduce from these results that in normal bone the general distribution of this tracer reflects mainly the arrangement of the blood supply, but the specific sites of accumulation are the bone-forming surfaces and the active resorbing osteoclasts.", "contents": "Skeletal uptake of pyrophosphate labeled with technetium-95m and technetium-96, as evaluated by autoradiography. For animal experimentation, the 95m and 96 technetium isotopes offer many advantages over technetium-99m. Their long physical half-lives and the emission of extranuclear electrons of low penetrating power make it possible to obtain autoradiograms of a great precision. The uptake of technetium stannous pyrophosphate by the epiphyseal plate was studied using liquid-emulsion microautoradiography, 3 hr after i.v. injection into 10-week-old rabbits. Microautoradiograms showed a well-defined and rather specific pattern of localization with intense uptake beneath the epiphyseal disk on the extremities of the vascular buds and a lack of accumulation in the cartilage, whether calcified or uncalcified. In the metaphysis, the label was located where new bone was being laid down and also over the cytoplasm of osteoclasts. We deduce from these results that in normal bone the general distribution of this tracer reflects mainly the arrangement of the blood supply, but the specific sites of accumulation are the bone-forming surfaces and the active resorbing osteoclasts."}
{"id": "PMID:210269", "title": "Cystosarcoma phylloides in the adolescent female.", "content": "Two cases of cystosarcoma phylloides in the adolescent female are presented and the literature reviewed. This lesion is usually benign. Even when malignant, simple excision has been curative in 2 or 3 cases. Therapy recommended is local excision with a small margin of normal tissue.", "contents": "Cystosarcoma phylloides in the adolescent female. Two cases of cystosarcoma phylloides in the adolescent female are presented and the literature reviewed. This lesion is usually benign. Even when malignant, simple excision has been curative in 2 or 3 cases. Therapy recommended is local excision with a small margin of normal tissue."}
{"id": "PMID:210270", "title": "Calcific thrombi of the inferior vena cava in infants and children.", "content": "Calcified caval thrombus should be considered in any infant or child where calcifications are noted in the high right retroperitoneal area on plain x-rays of the abdomen. Although typically bullet-shaped in configuration, the calcium distribution in the neonate may be atypical or incompletely developed, suggesting neuroblastoma. Definitive diagnosis can be made by inferior vena cavagram. As no deaths or complications have been attributed to the lesion in the cases thus far reported, no specific treatment is recommended.", "contents": "Calcific thrombi of the inferior vena cava in infants and children. Calcified caval thrombus should be considered in any infant or child where calcifications are noted in the high right retroperitoneal area on plain x-rays of the abdomen. Although typically bullet-shaped in configuration, the calcium distribution in the neonate may be atypical or incompletely developed, suggesting neuroblastoma. Definitive diagnosis can be made by inferior vena cavagram. As no deaths or complications have been attributed to the lesion in the cases thus far reported, no specific treatment is recommended."}
{"id": "PMID:210272", "title": "REM motivation induced by brief REM deprivation: the influence of cognition, gender, and personality.", "content": "Prominence of the brain's right-hemisphere information processing and intensity of dream experience are two theoretically related constructs that have been proposed as important psychological aspects of REM sleep. Either view is consistent with the prediction that the effect of REM deprivation will depend in part on the nature of cognitive activity that is initiated at the onset of each REM period and that \"substitutes\" for the interrupted REM process. In the present study, the effect of REM deprivation was more striking for female subjects given a digits task than for female subjects given a fantasy-reporting task during awakening used to induce REM deprivation for the first 6 hours of the night. High neuroticism appeared to exaggerate the effect. No corresponding pattern was observed for the male subjects. These preliminary finding may be exaggerated by cognitive activity that is functionally incongruent with those processes. The results also raise interesting questions about individual differences.", "contents": "REM motivation induced by brief REM deprivation: the influence of cognition, gender, and personality. Prominence of the brain's right-hemisphere information processing and intensity of dream experience are two theoretically related constructs that have been proposed as important psychological aspects of REM sleep. Either view is consistent with the prediction that the effect of REM deprivation will depend in part on the nature of cognitive activity that is initiated at the onset of each REM period and that \"substitutes\" for the interrupted REM process. In the present study, the effect of REM deprivation was more striking for female subjects given a digits task than for female subjects given a fantasy-reporting task during awakening used to induce REM deprivation for the first 6 hours of the night. High neuroticism appeared to exaggerate the effect. No corresponding pattern was observed for the male subjects. These preliminary finding may be exaggerated by cognitive activity that is functionally incongruent with those processes. The results also raise interesting questions about individual differences."}
{"id": "PMID:210275", "title": "The mechanism of chlorothiazide-induced carbohydrate intolerance.", "content": "In order to establish the mechanism(s) of chlorothiazide-induced hyperglycemia, measurements of blood glucose, plasma insulin, liver glycogen and hepatic cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels, and liver phosphodiesterase activity were made in rats administered 10, 25, 50 or 100 mg/kg of the drug. Comparison of data obtained on these animals with those from controls revealed significant and dose-dependent increases in blood glucose, decreases in liver glycogen, increases in hepatic cyclic AMP and inhibition of phosphodiesterase. Although basal insulin levels were significantly increased at the two higher doses of chlorothiazide, ratios of blood glucose/plasma insulin levels showed suppression of insulin secretion at all four doses. However, this suppression was not dose-related. All effects of the drug were maximal at 2 hours after subcutaneous administration. The results of this investigation indicate that the primary mechanism of chlorothiazide-induced carbohydrate intolerance is cyclic AMP-mediated stimulation of glycogenolysis and inhibition of glycogenesis. Suppression of insulin secretion is secondary but probably contributes to the hyperglycemia.", "contents": "The mechanism of chlorothiazide-induced carbohydrate intolerance. In order to establish the mechanism(s) of chlorothiazide-induced hyperglycemia, measurements of blood glucose, plasma insulin, liver glycogen and hepatic cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels, and liver phosphodiesterase activity were made in rats administered 10, 25, 50 or 100 mg/kg of the drug. Comparison of data obtained on these animals with those from controls revealed significant and dose-dependent increases in blood glucose, decreases in liver glycogen, increases in hepatic cyclic AMP and inhibition of phosphodiesterase. Although basal insulin levels were significantly increased at the two higher doses of chlorothiazide, ratios of blood glucose/plasma insulin levels showed suppression of insulin secretion at all four doses. However, this suppression was not dose-related. All effects of the drug were maximal at 2 hours after subcutaneous administration. The results of this investigation indicate that the primary mechanism of chlorothiazide-induced carbohydrate intolerance is cyclic AMP-mediated stimulation of glycogenolysis and inhibition of glycogenesis. Suppression of insulin secretion is secondary but probably contributes to the hyperglycemia."}
{"id": "PMID:210277", "title": "Neuraminidase production by clostridia.", "content": "The production of neuraminidase (EC 3.2.1.18) by a range of clostridial species was investigated with techniques previously developed to distinguish neuraminidase-negative and neuraminidase-positive strains of Clostridium perfringens (welchii). Large amounts of extracellular neuraminidase were produced by representative strains of C. perfringens and C. septicum in the test media. Under similar conditions, two strains each of C. chauvoei and C. tertium were found to produce small amounts of the enzyme. All of 12 strains of C. sordellii were clearly shown to produce neuraminidase, often in large amounts, but none of five strains of the closely related but non-pathogenic C. bifermentans had demonstrable neuraminidase activity. No neuraminidase was produced by C. novyi (oedematiens) types A-D (10 strains), C. tetani (6), C. botulinum types A, B, C or E (4), C. sporogenes (4), C. histolyticum (4) or by single strains of five other clostridial species. Clostridial neuraminidase was predominantly extracellular and was not calcium-dependent. The investigation took account of variations in growth and enzyme production in different media. It was necessary to prolong the neuraminidase-assay reaction time to 24 h and to monitor for the presence of NAN-aldolase (EC 4.1.3.3) to define true negatives. It is suggested that neuraminidase production may be of value in taxonomic studies and that its production by several pathogenic species of clostridia may be of interest in studies of pathogenicity and virulence.", "contents": "Neuraminidase production by clostridia. The production of neuraminidase (EC 3.2.1.18) by a range of clostridial species was investigated with techniques previously developed to distinguish neuraminidase-negative and neuraminidase-positive strains of Clostridium perfringens (welchii). Large amounts of extracellular neuraminidase were produced by representative strains of C. perfringens and C. septicum in the test media. Under similar conditions, two strains each of C. chauvoei and C. tertium were found to produce small amounts of the enzyme. All of 12 strains of C. sordellii were clearly shown to produce neuraminidase, often in large amounts, but none of five strains of the closely related but non-pathogenic C. bifermentans had demonstrable neuraminidase activity. No neuraminidase was produced by C. novyi (oedematiens) types A-D (10 strains), C. tetani (6), C. botulinum types A, B, C or E (4), C. sporogenes (4), C. histolyticum (4) or by single strains of five other clostridial species. Clostridial neuraminidase was predominantly extracellular and was not calcium-dependent. The investigation took account of variations in growth and enzyme production in different media. It was necessary to prolong the neuraminidase-assay reaction time to 24 h and to monitor for the presence of NAN-aldolase (EC 4.1.3.3) to define true negatives. It is suggested that neuraminidase production may be of value in taxonomic studies and that its production by several pathogenic species of clostridia may be of interest in studies of pathogenicity and virulence."}
{"id": "PMID:210278", "title": "The use of an immunoperoxidase technique to investigate by light and electron microscopy the sites of binding of Clostridium welchii type-D epsilon toxin in mice.", "content": "Mice were given an intravenous dose of formalinised C. welchii type-D epsilon prototoxin and an immunoperoxidase technique was used to demonstrate this antigen in the tissues. The antigen was found to bind to the luminal surface of the endothelial lining of certain blood vessels, to the luminal surface of the cells lining the loops of Henl\u00e9 and distal convoluted tubules in the kidney, and to the hepatic sinusoids. As it has been shown previously that formalinised epsilon prototoxin and epsilon toxin can compete for the same receptor sites it is postulated that the binding sites demonstrated represent the location of the receptors for C. welchii type-D epsilon toxin.", "contents": "The use of an immunoperoxidase technique to investigate by light and electron microscopy the sites of binding of Clostridium welchii type-D epsilon toxin in mice. Mice were given an intravenous dose of formalinised C. welchii type-D epsilon prototoxin and an immunoperoxidase technique was used to demonstrate this antigen in the tissues. The antigen was found to bind to the luminal surface of the endothelial lining of certain blood vessels, to the luminal surface of the cells lining the loops of Henl\u00e9 and distal convoluted tubules in the kidney, and to the hepatic sinusoids. As it has been shown previously that formalinised epsilon prototoxin and epsilon toxin can compete for the same receptor sites it is postulated that the binding sites demonstrated represent the location of the receptors for C. welchii type-D epsilon toxin."}
{"id": "PMID:210279", "title": "In-vitro effects of Clostridium welchii type-D epsilon toxin on guinea-pig, mouse, rabbit and sheep cells.", "content": "Epsilon toxin, at relatively low concentrations, killed guinea-pig peritoneal macrophages in vitro. The cells became swollen, the nuclear and cytoplasmic membranes \"blistered\" and discontinuous, and the cytoplasm appeared structureless. Formalinised epsilon prototoxin was shown to bind closely to the outer surface of the cells and it is concluded that this site represents the location of the receptors for epsilon toxin. In addition the toxin at higher concentrations killed rabbit peritoneal macrophages after increased periods of incubation, but had no demonstrable effect on other cells from guinea-pigs, rabbits, mice and sheep.", "contents": "In-vitro effects of Clostridium welchii type-D epsilon toxin on guinea-pig, mouse, rabbit and sheep cells. Epsilon toxin, at relatively low concentrations, killed guinea-pig peritoneal macrophages in vitro. The cells became swollen, the nuclear and cytoplasmic membranes \"blistered\" and discontinuous, and the cytoplasm appeared structureless. Formalinised epsilon prototoxin was shown to bind closely to the outer surface of the cells and it is concluded that this site represents the location of the receptors for epsilon toxin. In addition the toxin at higher concentrations killed rabbit peritoneal macrophages after increased periods of incubation, but had no demonstrable effect on other cells from guinea-pigs, rabbits, mice and sheep."}
{"id": "PMID:210280", "title": "Serial studies of virus multiplication and intestinal damage in gnotobiotic piglets infected with rotavirus.", "content": "A serial study of rotavirus infection in gnotobiotic piglets is described. They were infected when 7 days old and the course of infection was followed for 21 days, by immunofluorescence and histological examinations of the intestinal epithelium and by titration of the virus content of the gut lumen. There appeared to be two stages of recovery of the intestinal wall, the earlier stage involving non-immune mechanisms and the later invloving antibody.", "contents": "Serial studies of virus multiplication and intestinal damage in gnotobiotic piglets infected with rotavirus. A serial study of rotavirus infection in gnotobiotic piglets is described. They were infected when 7 days old and the course of infection was followed for 21 days, by immunofluorescence and histological examinations of the intestinal epithelium and by titration of the virus content of the gut lumen. There appeared to be two stages of recovery of the intestinal wall, the earlier stage involving non-immune mechanisms and the later invloving antibody."}
{"id": "PMID:210282", "title": "Rapid microwave fixation of rat brain.", "content": "A new microwave device which inactivates brain enzymes rapidly and uniformly is described. From the results obtained with microwave irradiation at two power levels (0.8 kW and 4.5 kW), it has been demonstrated that the high power microwave irradiation has several advantages over the low power irradiation. In its application to neurochemical studies, significant increase in the DOPAC level was found in the irradiated brain, while there were no statistical differences in the levels of NE, DA, 5-HT and 5-HIAA between microwave irradiation and decapitation. Significant increase in the Ach level and marked reduction of the choline level were observed after microwave irradiation. There were no significant differences in the level of cyclic GMP in the brain between the two methods of sacrifice, while significant reduction of the cyclic AMP level was observed in the irradiated brain.", "contents": "Rapid microwave fixation of rat brain. A new microwave device which inactivates brain enzymes rapidly and uniformly is described. From the results obtained with microwave irradiation at two power levels (0.8 kW and 4.5 kW), it has been demonstrated that the high power microwave irradiation has several advantages over the low power irradiation. In its application to neurochemical studies, significant increase in the DOPAC level was found in the irradiated brain, while there were no statistical differences in the levels of NE, DA, 5-HT and 5-HIAA between microwave irradiation and decapitation. Significant increase in the Ach level and marked reduction of the choline level were observed after microwave irradiation. There were no significant differences in the level of cyclic GMP in the brain between the two methods of sacrifice, while significant reduction of the cyclic AMP level was observed in the irradiated brain."}
{"id": "PMID:210288", "title": "Multifocal nephroblastic neoplasia.", "content": "Among 23 patients with multifocal metanephric neoplasia were 14 patients with 43 grossly visible subcapsular tumorlets, 0.3-3.5 cm in diameter, that were apparently derived from nodular renal blastema. Tumorlets are defined as circumscribed lesions that are visible on the exterior surface of the kidney, produce either a raised nodule or, in a few instances, a shallow depression, and are independent of the main tumor(s). Most tumorlets displayed homogeneous epithelial maturation. A substantial minority of tumorlets retained a blastemic character and a few were histologically malignant. Tumorlets tended to be multiple and bilateral but were absent in 9 patients with multifocal disease, including 4 of 10 with bilateral tumors. About half the lesions that achieved tumorlet status, including those that gave rise to clinical tumors, underwent malignant transformation. Contralateral tumorlets should not be mistaken for metastasis and do not adversely affect prognosis. The incidence of neoplasia among young, close relatives of patients with multifocal disease appeared to be excessive, but no clear excess of major anomalies, hemihypertrophy, or minor genitourinary tract anomalies was revealed by a retrospective survey of hospital charts.", "contents": "Multifocal nephroblastic neoplasia. Among 23 patients with multifocal metanephric neoplasia were 14 patients with 43 grossly visible subcapsular tumorlets, 0.3-3.5 cm in diameter, that were apparently derived from nodular renal blastema. Tumorlets are defined as circumscribed lesions that are visible on the exterior surface of the kidney, produce either a raised nodule or, in a few instances, a shallow depression, and are independent of the main tumor(s). Most tumorlets displayed homogeneous epithelial maturation. A substantial minority of tumorlets retained a blastemic character and a few were histologically malignant. Tumorlets tended to be multiple and bilateral but were absent in 9 patients with multifocal disease, including 4 of 10 with bilateral tumors. About half the lesions that achieved tumorlet status, including those that gave rise to clinical tumors, underwent malignant transformation. Contralateral tumorlets should not be mistaken for metastasis and do not adversely affect prognosis. The incidence of neoplasia among young, close relatives of patients with multifocal disease appeared to be excessive, but no clear excess of major anomalies, hemihypertrophy, or minor genitourinary tract anomalies was revealed by a retrospective survey of hospital charts."}
{"id": "PMID:210289", "title": "Superoxide dismutase activity of normal murine liver, regenerating liver, and H6 hepatoma.", "content": "By means of both direct assay and gel electrophoresis, normal A/J mouse liver was shown to possess both Cu-Zn and Mn superoxide dismutase (SD) activity. H6 hepatoma cells contained Cu-Zn SD activity, but no Mn SD activity was detectable. Isolated mitochondria from normal liver contained both forms of the enzyme, but isolated mitochondria from H6 hepatoma cells contained no SD activity. To ascertain whether this loss of Mn SD activity was characteristic of these tumor cells or was simply a property of rapidly dividing cells, SD activity was measured in regenerating liver. Mn SD activity was present in the regenerating liver at all times after surgery. Hence loss of the Mn SD activity seemed to be a characteristic of some tumor cells but not of corresponding rapidly dividing normal cells.", "contents": "Superoxide dismutase activity of normal murine liver, regenerating liver, and H6 hepatoma. By means of both direct assay and gel electrophoresis, normal A/J mouse liver was shown to possess both Cu-Zn and Mn superoxide dismutase (SD) activity. H6 hepatoma cells contained Cu-Zn SD activity, but no Mn SD activity was detectable. Isolated mitochondria from normal liver contained both forms of the enzyme, but isolated mitochondria from H6 hepatoma cells contained no SD activity. To ascertain whether this loss of Mn SD activity was characteristic of these tumor cells or was simply a property of rapidly dividing cells, SD activity was measured in regenerating liver. Mn SD activity was present in the regenerating liver at all times after surgery. Hence loss of the Mn SD activity seemed to be a characteristic of some tumor cells but not of corresponding rapidly dividing normal cells."}
{"id": "PMID:210290", "title": "Suppressed murine mammary tumor virus (MuMTV) expression in RIII female mice treated neonatally with goat antiserum to MuMTV.", "content": "Passive immunization of newborn inbred RIII (R3) mice with the globulin fraction of goat antiserum to murine mammary tumor virus (MuMTV) successfully suppressed MuMTV expression in the milk of some of the treated mice throughout nine successive lactations. No mammary tumors developed in the MuMTV-suppressed mice during the first 9 months, whereas all untreated R3 female breeders expressed MuMTV in the milk of the third lactation, and all developed tumors before 9 months of age (mode and median: 189 days).", "contents": "Suppressed murine mammary tumor virus (MuMTV) expression in RIII female mice treated neonatally with goat antiserum to MuMTV. Passive immunization of newborn inbred RIII (R3) mice with the globulin fraction of goat antiserum to murine mammary tumor virus (MuMTV) successfully suppressed MuMTV expression in the milk of some of the treated mice throughout nine successive lactations. No mammary tumors developed in the MuMTV-suppressed mice during the first 9 months, whereas all untreated R3 female breeders expressed MuMTV in the milk of the third lactation, and all developed tumors before 9 months of age (mode and median: 189 days)."}
{"id": "PMID:210291", "title": "Differential effects of beta-naphthoflavone and pregnenolone-16alpha-carbonitrile on dimethylnitrosamine-induced hepatocarcinogenesis.", "content": "The effect of administration of beta-naphthoflavone (beta-NF) or pregnenolone-16alpha-carbonitrile (PCN) on the hepatocarcinogenicity of dimethylnitrosamine (DMN) in male SD rats was explored. Both beta-NF and PCN are potent repressors of the low Michaelis constant enzymatic form of DMN-demethylase, a mixed-function oxidase that catalyzes DMN demethylation. DMN-induced hepatocarcinogenesis was inhibited by PCN and was enhanced by beta-NF. Seven liver tumors were found in 45 rats fed DMN plus PCN compared to 14 liver tumors in 43 rats fed DMN alone; 32 liver tumors were found in 43 rats fed DMN plus beta-NF. No liver tumors were detected in rats that received only PCN, beta-NF, or the administration vehicles. Of the 53 liver tumors observed, 53% were angiosarcomas; this type of tumor was found in all 3 groups of rats that received DMN.", "contents": "Differential effects of beta-naphthoflavone and pregnenolone-16alpha-carbonitrile on dimethylnitrosamine-induced hepatocarcinogenesis. The effect of administration of beta-naphthoflavone (beta-NF) or pregnenolone-16alpha-carbonitrile (PCN) on the hepatocarcinogenicity of dimethylnitrosamine (DMN) in male SD rats was explored. Both beta-NF and PCN are potent repressors of the low Michaelis constant enzymatic form of DMN-demethylase, a mixed-function oxidase that catalyzes DMN demethylation. DMN-induced hepatocarcinogenesis was inhibited by PCN and was enhanced by beta-NF. Seven liver tumors were found in 45 rats fed DMN plus PCN compared to 14 liver tumors in 43 rats fed DMN alone; 32 liver tumors were found in 43 rats fed DMN plus beta-NF. No liver tumors were detected in rats that received only PCN, beta-NF, or the administration vehicles. Of the 53 liver tumors observed, 53% were angiosarcomas; this type of tumor was found in all 3 groups of rats that received DMN."}
{"id": "PMID:210292", "title": "Prevalence of murine mammary tumor virus antibody and antigens in normal and tumor-bearing feral mice.", "content": "Approximately 20% of normal male and female feral mice (Mus musculus) from areas with populations having either high [Lake Casitas (LC) and La Puente] or low (Bouquet Canyon) spontaneous lymphoma incidence expressed murine mammary tumor virus (MuMTV) gp52 in specific tissues. Sera from a low percentage (6%) of mice from the same trapping areas contained precipitating antibody specific for MuMTV. Although moderate to high levels of MuMTV gp52 were expressed in mammary tumor tissues of 3 of 7 LC mice and 3 of 3 (C57BL/10ScSn X LC)F1 mice, the same animals showed no detectable MuMTV-precipitating antibody. Neither MuMTV antibody nor tumor-associated MuMTV gp52 was defected in 10 LC mice bearing lymphomas or in 5 LC mice bearing hepatomas. Low levels of MuMTV gp52 expression and MuMTV antibody were also detected in subspecies of M. musculus and in the more distantly related species M. cervicolar. Compared with normal and tumor-bearing inbred mice of high (C3H/HeN) and low (C3H/HeN foster-nursed on NIH Swiss) mammary tumor strains, normal and tumor-bearing feral mice express MuMTV gp52 and MuMTV-precipitating antibodies at low frequency.", "contents": "Prevalence of murine mammary tumor virus antibody and antigens in normal and tumor-bearing feral mice. Approximately 20% of normal male and female feral mice (Mus musculus) from areas with populations having either high [Lake Casitas (LC) and La Puente] or low (Bouquet Canyon) spontaneous lymphoma incidence expressed murine mammary tumor virus (MuMTV) gp52 in specific tissues. Sera from a low percentage (6%) of mice from the same trapping areas contained precipitating antibody specific for MuMTV. Although moderate to high levels of MuMTV gp52 were expressed in mammary tumor tissues of 3 of 7 LC mice and 3 of 3 (C57BL/10ScSn X LC)F1 mice, the same animals showed no detectable MuMTV-precipitating antibody. Neither MuMTV antibody nor tumor-associated MuMTV gp52 was defected in 10 LC mice bearing lymphomas or in 5 LC mice bearing hepatomas. Low levels of MuMTV gp52 expression and MuMTV antibody were also detected in subspecies of M. musculus and in the more distantly related species M. cervicolar. Compared with normal and tumor-bearing inbred mice of high (C3H/HeN) and low (C3H/HeN foster-nursed on NIH Swiss) mammary tumor strains, normal and tumor-bearing feral mice express MuMTV gp52 and MuMTV-precipitating antibodies at low frequency."}
{"id": "PMID:210293", "title": "Chromosome banding patterns and breakpoints of three transplantable hepatomas induced in rats by aromatic amines.", "content": "The chromosome constitution of transplantable hepatomas H-35tc1, 7316A, and 8994 induced in ACI male, BUF female, and BUF male rats, respectively, by monocyclic or polycyclic aromatic amines was studied by Giemsa banding techniques. Hepatoma H-35tc1 was hyperdiploid, with a dominant stemline of 46 chromosomes. The stemline of the heterogeneous 7316A was in the hypotetraploid region (75-8,). Hepatoma 8994 had a near-triploid complement; most metaphase cells and chromosome numbers from 62 to 68. Thirty marker chromosomes were detected. Nineteen rearanged chromosomes were in hepatoma 8994, whereas only 8-10 markers could be found in the 80 +/- 3 chromosome complement of hepatoma 7316A. Two constant common markers were noted: mar2, a chromosome No. 11 with translocation short arm in H-35tc1 and 8994, and mar10 (mar10a), a chromosome No. 1 with a duplicated segment at breakpoint q54 in hepatomas 7316A and 8994. An analysis of the distribution of 232 breakpoints in the rat karyotype, 26 identified in the hepatomas and 206 collected from the literature, revealed a statistically significant excess of breaks in chromosomes No. 1, 2, 3, and 10 (P less than 0.001). The X- and Y-chromosomes showed a considerably lower number of breaks than anticipated (P less than 0.01). Even after a history of continuous transplantation for 10 years, these 3 hepatomas retained intact sex chromosomes that corresponded to the phenotype of the primary host. Preservation of the sex chromosomes in the hepatomas may be attributed to a lower susceptibility of the sex chromosomes than of the autosomes to breakage.", "contents": "Chromosome banding patterns and breakpoints of three transplantable hepatomas induced in rats by aromatic amines. The chromosome constitution of transplantable hepatomas H-35tc1, 7316A, and 8994 induced in ACI male, BUF female, and BUF male rats, respectively, by monocyclic or polycyclic aromatic amines was studied by Giemsa banding techniques. Hepatoma H-35tc1 was hyperdiploid, with a dominant stemline of 46 chromosomes. The stemline of the heterogeneous 7316A was in the hypotetraploid region (75-8,). Hepatoma 8994 had a near-triploid complement; most metaphase cells and chromosome numbers from 62 to 68. Thirty marker chromosomes were detected. Nineteen rearanged chromosomes were in hepatoma 8994, whereas only 8-10 markers could be found in the 80 +/- 3 chromosome complement of hepatoma 7316A. Two constant common markers were noted: mar2, a chromosome No. 11 with translocation short arm in H-35tc1 and 8994, and mar10 (mar10a), a chromosome No. 1 with a duplicated segment at breakpoint q54 in hepatomas 7316A and 8994. An analysis of the distribution of 232 breakpoints in the rat karyotype, 26 identified in the hepatomas and 206 collected from the literature, revealed a statistically significant excess of breaks in chromosomes No. 1, 2, 3, and 10 (P less than 0.001). The X- and Y-chromosomes showed a considerably lower number of breaks than anticipated (P less than 0.01). Even after a history of continuous transplantation for 10 years, these 3 hepatomas retained intact sex chromosomes that corresponded to the phenotype of the primary host. Preservation of the sex chromosomes in the hepatomas may be attributed to a lower susceptibility of the sex chromosomes than of the autosomes to breakage."}
{"id": "PMID:210294", "title": "Control of melanogenesis in mouse melanoma cells of varying metastatic potential.", "content": "The control of melanin production, tyrosinase activity, and cell replication by melanocyte-stimulating hormone (MSH) and cyclic AMP (cAMP) was examined in differentially metastasizing B16 mouse melanoma variants. In B16-F1 cells (low metastatic potential), MSH or cAMP greatly elevated tyrosinase activity and melanin content while inhibiting cell replication. The same parameters in B16-F5 cells (intermediate metastatic potential) were altered to a much lesser degree, whereas B16-F10 cells (high metastatic potential) were not significantly affected by MSH or cAMP. Therefore, a correlation exists between loss of hormonal regulation and increased metastatic potential.", "contents": "Control of melanogenesis in mouse melanoma cells of varying metastatic potential. The control of melanin production, tyrosinase activity, and cell replication by melanocyte-stimulating hormone (MSH) and cyclic AMP (cAMP) was examined in differentially metastasizing B16 mouse melanoma variants. In B16-F1 cells (low metastatic potential), MSH or cAMP greatly elevated tyrosinase activity and melanin content while inhibiting cell replication. The same parameters in B16-F5 cells (intermediate metastatic potential) were altered to a much lesser degree, whereas B16-F10 cells (high metastatic potential) were not significantly affected by MSH or cAMP. Therefore, a correlation exists between loss of hormonal regulation and increased metastatic potential."}
{"id": "PMID:210295", "title": "Suppression and immunotherapy of the guinea pig line-10 hepatocarcinoma mediated by nonviable Staphylococcus aureus.", "content": "Suppression of growth of the line-10 guinea pig hepatocarcinoma was achieved after the simultaneous injection of line-10 cells and heat-killed Staphylococcus aureus. Growth of tumor was also suppressed when line-10 cells were injected alone, contralaterally, at the same time as the vaccine mixture. Immunity developed to subsequent line-10 cell challenges but not to other syngeneic tumors. Similar results were obtained with the use of protein A-rich or -deficient strains of S. aureus. Multiple intratumor injections of heat-killed S. aureus were therapeutically effective against 6-day tumors. The antitumor effects of nonviable S. aureus were similar in many ways to those of living BCG or bacterial products suspended in oil droplets.", "contents": "Suppression and immunotherapy of the guinea pig line-10 hepatocarcinoma mediated by nonviable Staphylococcus aureus. Suppression of growth of the line-10 guinea pig hepatocarcinoma was achieved after the simultaneous injection of line-10 cells and heat-killed Staphylococcus aureus. Growth of tumor was also suppressed when line-10 cells were injected alone, contralaterally, at the same time as the vaccine mixture. Immunity developed to subsequent line-10 cell challenges but not to other syngeneic tumors. Similar results were obtained with the use of protein A-rich or -deficient strains of S. aureus. Multiple intratumor injections of heat-killed S. aureus were therapeutically effective against 6-day tumors. The antitumor effects of nonviable S. aureus were similar in many ways to those of living BCG or bacterial products suspended in oil droplets."}
{"id": "PMID:210296", "title": "The respiratory epithelium. V. Histogenesis of lung carcinomas in the human.", "content": "One hundred human primary lung carcinomas were studied by light and electron microscopy and by light microscopic histochemistry to demonstrate mucosubstances. The tumors were classified histogenetically and were grouped into three major categories depending on their cell of origin: 1) tumors from basal and/or mucous cells; 2) tumors from neurosecretory cells; and 3) tumors from Clara cells. Most carcinomas (88%) arose from basal and/or mucous cells. These were subdivided into epidermoid carcinomas (21%), combined epidermoid and adenocarcinomas (46%), and adenocarcinomas (21%). The criteria for epidermoid differentiation included the presence of tonofilament bundles, poorly developed endoplasmic reticulum and Golgi apparatus, and well-developed desmosomes. The criteria for adeno differentiation included well-developed endoplasmic reticulum and Golgi apparatus, poorly developed desmosomes, the presence of extracellular and/or intracellular alveoli, and/or other evidence of cellular secretion such as secretory granules. In adenocarcinomas with extracellular alveoli, typical junctional complexes were also present at the luminal aspect where the cell apexes bordered the alveolus. With these criteria, combined epidermoid and adenocarcinomas were the most common type of lung carcinoma. We anticipate that the new data will clarify categories such as small cell anaplastic carcinoma and large cell carcinoma of the World Health Organization classification. In addition, the histogenetic classification of lung tumors may be of value in the future in studies of risk factors, prognosis, prevention, and treatment of lung cancer.", "contents": "The respiratory epithelium. V. Histogenesis of lung carcinomas in the human. One hundred human primary lung carcinomas were studied by light and electron microscopy and by light microscopic histochemistry to demonstrate mucosubstances. The tumors were classified histogenetically and were grouped into three major categories depending on their cell of origin: 1) tumors from basal and/or mucous cells; 2) tumors from neurosecretory cells; and 3) tumors from Clara cells. Most carcinomas (88%) arose from basal and/or mucous cells. These were subdivided into epidermoid carcinomas (21%), combined epidermoid and adenocarcinomas (46%), and adenocarcinomas (21%). The criteria for epidermoid differentiation included the presence of tonofilament bundles, poorly developed endoplasmic reticulum and Golgi apparatus, and well-developed desmosomes. The criteria for adeno differentiation included well-developed endoplasmic reticulum and Golgi apparatus, poorly developed desmosomes, the presence of extracellular and/or intracellular alveoli, and/or other evidence of cellular secretion such as secretory granules. In adenocarcinomas with extracellular alveoli, typical junctional complexes were also present at the luminal aspect where the cell apexes bordered the alveolus. With these criteria, combined epidermoid and adenocarcinomas were the most common type of lung carcinoma. We anticipate that the new data will clarify categories such as small cell anaplastic carcinoma and large cell carcinoma of the World Health Organization classification. In addition, the histogenetic classification of lung tumors may be of value in the future in studies of risk factors, prognosis, prevention, and treatment of lung cancer."}
{"id": "PMID:210297", "title": "Spermatic cord sarcoma in adults.", "content": "The clinical courses are presented for 6 patients with sarcoma of the spermatic cord seen between 1967 and 1976. There were 3 fibrosarcomas, 2 liposarcomas and 1 malignant fibrous histiocytoma, making the total reported cases of spermatic cord sarcoma 212. Management of spermatic cord sarcoma is discussed.", "contents": "Spermatic cord sarcoma in adults. The clinical courses are presented for 6 patients with sarcoma of the spermatic cord seen between 1967 and 1976. There were 3 fibrosarcomas, 2 liposarcomas and 1 malignant fibrous histiocytoma, making the total reported cases of spermatic cord sarcoma 212. Management of spermatic cord sarcoma is discussed."}
{"id": "PMID:210298", "title": "Nephroblastoma occurring in a multilocular cystic kidney.", "content": "A case of a nephroblastoma in a multilocular cystic kidney in a 5-year-old child is reported and the related literature is reviewed. Because of the unreliability of preoperative and intraoperative diagnostic modalities in identifying a coincidental nephroblastoma nephrectomy is recommended for multilocular cystic disease of the kidney in children.", "contents": "Nephroblastoma occurring in a multilocular cystic kidney. A case of a nephroblastoma in a multilocular cystic kidney in a 5-year-old child is reported and the related literature is reviewed. Because of the unreliability of preoperative and intraoperative diagnostic modalities in identifying a coincidental nephroblastoma nephrectomy is recommended for multilocular cystic disease of the kidney in children."}
{"id": "PMID:210299", "title": "Toward less hazardous cigarettes. Current advances.", "content": "Critical levels of selected cigarette smoke constituents have been expressed in terms of maximum numbers of pre-1960 cigarettes that a smoker may consume daily without increasing his mortality risk substantially above that of a nonsmoker. This could still imply an important risk, although it may be difficult to detect. We relate these levels to the yields of 27 current low tar and nicotine commercial cigarettes, as measured at the Oak Ridge National Laboratory. In addition, the yields of these selected constituents concomitant with the yield of 1 mg of nicotine are provided as a guide for the smoker who titrates or adjusts his smoking pattern to accommodate a fixed daily intake of nicotine.", "contents": "Toward less hazardous cigarettes. Current advances. Critical levels of selected cigarette smoke constituents have been expressed in terms of maximum numbers of pre-1960 cigarettes that a smoker may consume daily without increasing his mortality risk substantially above that of a nonsmoker. This could still imply an important risk, although it may be difficult to detect. We relate these levels to the yields of 27 current low tar and nicotine commercial cigarettes, as measured at the Oak Ridge National Laboratory. In addition, the yields of these selected constituents concomitant with the yield of 1 mg of nicotine are provided as a guide for the smoker who titrates or adjusts his smoking pattern to accommodate a fixed daily intake of nicotine."}
{"id": "PMID:210301", "title": "Pituitary pigmentary hormones. Relationship of melanocyte-stimulating hormone to lipotropic hormone.", "content": "Pituitary control of pigmentation has known for more than 60 years. Since 1969, beta-melanocyte-stimulating hormone (beta-MSH) has been accepted as the main pituitary pigmentary hormone in man. Its \"constant companionship\" with adrenocorticotrophic hormone (ACTH) has also been repeatedly demonstrated. Current investigations challenge both of these concepts. Human beta-MSH immunoreactivity has been shown to be actually due to beta-lipotropic hormone (beta-LPH), a larger molecule that within itself contains the entire amino acid sequence of beta-MSH. Human beta-MSH does not exist in vivo; it is merely an extraction artifact formed by enzymatic degradation of beta-LPH. It would appear likely that beta-LPH, not beta-MSH, is the constant companion of ACTH.", "contents": "Pituitary pigmentary hormones. Relationship of melanocyte-stimulating hormone to lipotropic hormone. Pituitary control of pigmentation has known for more than 60 years. Since 1969, beta-melanocyte-stimulating hormone (beta-MSH) has been accepted as the main pituitary pigmentary hormone in man. Its \"constant companionship\" with adrenocorticotrophic hormone (ACTH) has also been repeatedly demonstrated. Current investigations challenge both of these concepts. Human beta-MSH immunoreactivity has been shown to be actually due to beta-lipotropic hormone (beta-LPH), a larger molecule that within itself contains the entire amino acid sequence of beta-MSH. Human beta-MSH does not exist in vivo; it is merely an extraction artifact formed by enzymatic degradation of beta-LPH. It would appear likely that beta-LPH, not beta-MSH, is the constant companion of ACTH."}
{"id": "PMID:210302", "title": "Transfusion-related short-incubation hepatitis in hemophilic patients.", "content": "Nine episodes of a unique short-incubation form of hepatitis were observed during five years in six hemophilic children after infusion with commercial factor VIII concentrate prepared by two different manufacturers. Five patients with a single episode had no previous infusion for 14 months to 14 years. One patient with several episodes had no previous infusion for at least seven months preceding each episode. The illness was mild and self-limited. No seroconversions to cytomegalovirus, Epstein-Barr virus, toxoplasmosis, or hepatitis A virus occurred. Acute hepatitis B virus infection was also excluded. The findings suggest the presence of one or more non-A, non-B hepatitis agents associated with factor VIII concentrates.", "contents": "Transfusion-related short-incubation hepatitis in hemophilic patients. Nine episodes of a unique short-incubation form of hepatitis were observed during five years in six hemophilic children after infusion with commercial factor VIII concentrate prepared by two different manufacturers. Five patients with a single episode had no previous infusion for 14 months to 14 years. One patient with several episodes had no previous infusion for at least seven months preceding each episode. The illness was mild and self-limited. No seroconversions to cytomegalovirus, Epstein-Barr virus, toxoplasmosis, or hepatitis A virus occurred. Acute hepatitis B virus infection was also excluded. The findings suggest the presence of one or more non-A, non-B hepatitis agents associated with factor VIII concentrates."}
{"id": "PMID:210304", "title": "Congenital mesoblastic nephroma and polyhydramnios.", "content": "Polyhydramnios and premature delivery complicated the pregnancies of three women whose infants were born with renal tumors. In each case the tumor was a mesoblastic nephroma. The liquid of polyhydramnios enhances detection of masses in the fetal abdomen by ultrasound. In the future, mesoblastic nephroma may, therefore, be diagnosed antenatally. Tumors in these infants, which have proved in most cases to be benign, are usually cured by surgical removal. Occasionally, local infiltration and adhesions prevent removal. The fate of the infant with residual tumor is not known.", "contents": "Congenital mesoblastic nephroma and polyhydramnios. Polyhydramnios and premature delivery complicated the pregnancies of three women whose infants were born with renal tumors. In each case the tumor was a mesoblastic nephroma. The liquid of polyhydramnios enhances detection of masses in the fetal abdomen by ultrasound. In the future, mesoblastic nephroma may, therefore, be diagnosed antenatally. Tumors in these infants, which have proved in most cases to be benign, are usually cured by surgical removal. Occasionally, local infiltration and adhesions prevent removal. The fate of the infant with residual tumor is not known."}
{"id": "PMID:210309", "title": "Primary mucinous adenocarcinoma of the appendix with bilateral Krukenberg ovarian tumors.", "content": "After experiencing intermittent episodes of abdominal pain for two years, a 28-year-old woman developed partial small bowel obstruction. Barium enema and colonoscopy revealed the source of obstruction to be an apparent cecal carcinoma. At exploratory laparotomy a primary adenocarcinoma of the appendix with bilateral Krukenberg ovarian metastases was found. This is a rare occurrence and, to our knowledge, the first well-documented case in the English literature. These case also demonstrates difficulties in the preoperative diagnosis of adenocarcinoma of the appendix.", "contents": "Primary mucinous adenocarcinoma of the appendix with bilateral Krukenberg ovarian tumors. After experiencing intermittent episodes of abdominal pain for two years, a 28-year-old woman developed partial small bowel obstruction. Barium enema and colonoscopy revealed the source of obstruction to be an apparent cecal carcinoma. At exploratory laparotomy a primary adenocarcinoma of the appendix with bilateral Krukenberg ovarian metastases was found. This is a rare occurrence and, to our knowledge, the first well-documented case in the English literature. These case also demonstrates difficulties in the preoperative diagnosis of adenocarcinoma of the appendix."}
{"id": "PMID:210311", "title": "[Evaluation of renal cyclic adenosine monophosphate, serum parathyroid hormone and phosphate reabsorption in recurrent calcium urolithiasis, healthy controls and hyperparathyroidism (author's transl)].", "content": "In three groups (n = 12 each) of male controls (22--43 years), patients with recurring calcium urolithiasis (21--36 years) and hyperparathyroidism (HPT; 17--71 years) proven by surgery renal cyclic adenosine monophosphate (RcAMP), fractional tubular phosphate reabsorption and serum parathyroid hormone (PTH) were measured during endogenous creatinine clearance. RcAMP (muMol/g creatinine) was: controls 1.48 +/- SEM 0.27; stone formers 2.037 +/- 0.343 (not significantly different); HPT 6.234 +/- 0.454 (p less than 0.001). There is no overlap between HPT and controls. Phosphate reabsorption is least in HPT (0.84 +/- 0.015), higher in controls (0.924 +/- 0.004) and stone formers (0.941 +/- 0.007). All differences are statistically significant. Under the conditions selected (moderate hydration of individuals) Serum PHT (pg-equiv/ml) is lowest in stome formers (less than 100--339), higher in controls (less than 100--933) and HPT (400--1150). there is no overlap in PHT between the former and the latter group but a marked one between controls and HPT. For clinical purposes the resulting diagnostic uncertainty in a given patient can be overcome by additional determinations of RcAMP and ionised serum calcium: when referring to serum PTH HPT patients fall outside, RCU patients within 2 standard deviations of either parameter in control subjects. This procedure presently appears superior to those proposed in the past (urinary cAMP etc.) but requires confirmation in larger patient populations. Moreover, since HPT prevails in middle and upper age decades, their RcAMP values and those of RCU patients should be related to a range seen in closely age- and sex-matched controls.", "contents": "[Evaluation of renal cyclic adenosine monophosphate, serum parathyroid hormone and phosphate reabsorption in recurrent calcium urolithiasis, healthy controls and hyperparathyroidism (author's transl)]. In three groups (n = 12 each) of male controls (22--43 years), patients with recurring calcium urolithiasis (21--36 years) and hyperparathyroidism (HPT; 17--71 years) proven by surgery renal cyclic adenosine monophosphate (RcAMP), fractional tubular phosphate reabsorption and serum parathyroid hormone (PTH) were measured during endogenous creatinine clearance. RcAMP (muMol/g creatinine) was: controls 1.48 +/- SEM 0.27; stone formers 2.037 +/- 0.343 (not significantly different); HPT 6.234 +/- 0.454 (p less than 0.001). There is no overlap between HPT and controls. Phosphate reabsorption is least in HPT (0.84 +/- 0.015), higher in controls (0.924 +/- 0.004) and stone formers (0.941 +/- 0.007). All differences are statistically significant. Under the conditions selected (moderate hydration of individuals) Serum PHT (pg-equiv/ml) is lowest in stome formers (less than 100--339), higher in controls (less than 100--933) and HPT (400--1150). there is no overlap in PHT between the former and the latter group but a marked one between controls and HPT. For clinical purposes the resulting diagnostic uncertainty in a given patient can be overcome by additional determinations of RcAMP and ionised serum calcium: when referring to serum PTH HPT patients fall outside, RCU patients within 2 standard deviations of either parameter in control subjects. This procedure presently appears superior to those proposed in the past (urinary cAMP etc.) but requires confirmation in larger patient populations. Moreover, since HPT prevails in middle and upper age decades, their RcAMP values and those of RCU patients should be related to a range seen in closely age- and sex-matched controls."}
{"id": "PMID:210327", "title": "Isolation of mouse hepatitis virus from infant mice with fatal diarrhea.", "content": "An epizootic of fatal diarrhea occurred in mice which were approximately 10 days of age. The enteric lesions were similar to those reported in lethal intestinal virus of infant mice, but many diseased mice also had necrotic hepatitis. Mouse hepatitis virus antigen was demonstrated in the affected intestine and liver, and a virus that produced syncitium formation in mouse brain tumor cell culture was isolated from the intestines, livers, and brains. The virus was capable of producing intestinal and hepatic lesions similar to the naturally occurring disease after inoculation into suckling mice. Electron microscopy revealed viral particles within affected intestinal epithelial cells of the inoculated mice.", "contents": "Isolation of mouse hepatitis virus from infant mice with fatal diarrhea. An epizootic of fatal diarrhea occurred in mice which were approximately 10 days of age. The enteric lesions were similar to those reported in lethal intestinal virus of infant mice, but many diseased mice also had necrotic hepatitis. Mouse hepatitis virus antigen was demonstrated in the affected intestine and liver, and a virus that produced syncitium formation in mouse brain tumor cell culture was isolated from the intestines, livers, and brains. The virus was capable of producing intestinal and hepatic lesions similar to the naturally occurring disease after inoculation into suckling mice. Electron microscopy revealed viral particles within affected intestinal epithelial cells of the inoculated mice."}
{"id": "PMID:210328", "title": "Further observations on spontaneous neoplasms in the Mongolian gerbil, Meriones unguiculatus.", "content": "One hundred sixty Mongolian gerbils, Meriones unguiculatus, were examined for the presence of naturally occurring lesions. The first recognized cases of cecal adenocarcinoma, testicular teratoma, and sebaceous gland pad carcinoma were found. Neoplasms previously reported from the gerbil and also seen in the present study included ovarian theca lutein and granulosa lutein cell tumors, sebaceous gland pad adenoma, cutaneous squamous cell carcinoma, malignant melanoma, and renal and splenic hemangiomas. Calcinosis cutis was also observed in two male gerbils.", "contents": "Further observations on spontaneous neoplasms in the Mongolian gerbil, Meriones unguiculatus. One hundred sixty Mongolian gerbils, Meriones unguiculatus, were examined for the presence of naturally occurring lesions. The first recognized cases of cecal adenocarcinoma, testicular teratoma, and sebaceous gland pad carcinoma were found. Neoplasms previously reported from the gerbil and also seen in the present study included ovarian theca lutein and granulosa lutein cell tumors, sebaceous gland pad adenoma, cutaneous squamous cell carcinoma, malignant melanoma, and renal and splenic hemangiomas. Calcinosis cutis was also observed in two male gerbils."}
{"id": "PMID:210330", "title": "Cardiac paraganglioma (chemodectoma): a case report and review of the literature.", "content": "A rare case of paraganglioma (chemodectoma) of the heart is reported. This is the fifth case reported in the world literature and only the second case discovered in a living person. A review of the historical background, embryology, anatomy, and pathology of the paraganglia is provided. The previously reported four cases are also discussed.", "contents": "Cardiac paraganglioma (chemodectoma): a case report and review of the literature. A rare case of paraganglioma (chemodectoma) of the heart is reported. This is the fifth case reported in the world literature and only the second case discovered in a living person. A review of the historical background, embryology, anatomy, and pathology of the paraganglia is provided. The previously reported four cases are also discussed."}
{"id": "PMID:210331", "title": "Bronchoplastic procedures in the treatment of carcinoid tumors of the tracheobronchial tree.", "content": "Sixteen patients, aged 10 to 70 years, had carcinoid tumors of the lower respiratory tract treated by various resective tracheobronchoplastic procedures. These represent 8.8 percent of 181 patients with carcinoid lesions treated during a recent 20 year period. All 16 patients had respiratory symptoms, and one patient also had the carcinoid syndrome. Roentgenographic changes ranged from a mass or atelectasis (or both) through unilateral lung hyperinflation to clear lungs with subtle filling defects in major airways. All tumors were visualized endoscopically, and 13 patients had biopsies. Histopathologically, all tumors were \"typical\" carcinoids . Before operation, the patients had minimal or no respiratory insufficiency, although flow-volume and ventilation-perfusion abnormalities were noted when major airways were affected. Surgical management at thoracotomy was as follows: (1) simple wedge tracheobronchotomy without lung resection (five patients); (2) bronchial sleeve resection without lung resection (three patients); and (3) bronchial sleeve with upper lobe resection (eight patients). These 16 operations were performed with eight technical anatomic variations. No early or late deaths occurred. One patient had early transient atelectasis, and three patients required late endoscopic removal of suture granulation tissue. All patients were alive without recurrence of tumor or carcinoid syndrome or other respiratory complications 6 months to 19 years postoperatively. Pulmonary resection should be avoided unless there is histologic evidence of tumor extension into lung parenchyma or irreversible pulmonary suppuration distal to the obstructive tumor.", "contents": "Bronchoplastic procedures in the treatment of carcinoid tumors of the tracheobronchial tree. Sixteen patients, aged 10 to 70 years, had carcinoid tumors of the lower respiratory tract treated by various resective tracheobronchoplastic procedures. These represent 8.8 percent of 181 patients with carcinoid lesions treated during a recent 20 year period. All 16 patients had respiratory symptoms, and one patient also had the carcinoid syndrome. Roentgenographic changes ranged from a mass or atelectasis (or both) through unilateral lung hyperinflation to clear lungs with subtle filling defects in major airways. All tumors were visualized endoscopically, and 13 patients had biopsies. Histopathologically, all tumors were \"typical\" carcinoids . Before operation, the patients had minimal or no respiratory insufficiency, although flow-volume and ventilation-perfusion abnormalities were noted when major airways were affected. Surgical management at thoracotomy was as follows: (1) simple wedge tracheobronchotomy without lung resection (five patients); (2) bronchial sleeve resection without lung resection (three patients); and (3) bronchial sleeve with upper lobe resection (eight patients). These 16 operations were performed with eight technical anatomic variations. No early or late deaths occurred. One patient had early transient atelectasis, and three patients required late endoscopic removal of suture granulation tissue. All patients were alive without recurrence of tumor or carcinoid syndrome or other respiratory complications 6 months to 19 years postoperatively. Pulmonary resection should be avoided unless there is histologic evidence of tumor extension into lung parenchyma or irreversible pulmonary suppuration distal to the obstructive tumor."}
{"id": "PMID:210332", "title": "Combined therapy for small cell undifferentiated carcinoma of the lung.", "content": "Fifty-eight patients with small cell lung cancer were treated from September, 1974, to March, 1976, with combined chemotherapy and radiotherapy. Surgical resection of the lung lesion was performed in three patients, and a number of surgical diagnostic methods were carried out in the remaining patients with unresectable of disseminated lesions. Nineteen patients were from the Veterans Administration Hospital and 39 from Indiana University Medical Center. The median Karnofsky performance status was 60. Thirty-nine patients had extensive disease, and 19 had disease limited to the chest and supraclavicular area. All patients received chest radiotherapy and prophylactic whole brain radiation. Adriamycin, cyclophosphamide, and vincristine were given on day 1 and continued every 3 weeks. There were 27 (48 percent) partial remissions of a median duration of 26 weeks. There were 25 patients (43 percent) with complete remission. The median survival for the entire group was 51 weeks. Six of 58 patients (10 percent) are alive and disease free from 24 to 38 months after treatment. Six of 19 patients with limited disease (32 percent) are presently alive and disease free. This includes one patient in whom surgical resection was performed. Combined therapy influences favorably the prognosis of small cell cancer of the ling, expecially in those patients with limited disease and favorable performance status.", "contents": "Combined therapy for small cell undifferentiated carcinoma of the lung. Fifty-eight patients with small cell lung cancer were treated from September, 1974, to March, 1976, with combined chemotherapy and radiotherapy. Surgical resection of the lung lesion was performed in three patients, and a number of surgical diagnostic methods were carried out in the remaining patients with unresectable of disseminated lesions. Nineteen patients were from the Veterans Administration Hospital and 39 from Indiana University Medical Center. The median Karnofsky performance status was 60. Thirty-nine patients had extensive disease, and 19 had disease limited to the chest and supraclavicular area. All patients received chest radiotherapy and prophylactic whole brain radiation. Adriamycin, cyclophosphamide, and vincristine were given on day 1 and continued every 3 weeks. There were 27 (48 percent) partial remissions of a median duration of 26 weeks. There were 25 patients (43 percent) with complete remission. The median survival for the entire group was 51 weeks. Six of 58 patients (10 percent) are alive and disease free from 24 to 38 months after treatment. Six of 19 patients with limited disease (32 percent) are presently alive and disease free. This includes one patient in whom surgical resection was performed. Combined therapy influences favorably the prognosis of small cell cancer of the ling, expecially in those patients with limited disease and favorable performance status."}
{"id": "PMID:210333", "title": "Adenoid cystic carcinoma (cylindroma) and mucoepidermoid carcinoma of the bronchus. Factors affecting survival.", "content": "A review was made of the presentation, treatment, and follow-up of 20 patients with adenoid cystic carcinoma and 12 patients with mucoepidermoid carcinoma of the bronchus who were seen at the Mayo Clinic during the 50 year period 1927 through 1977. Three forms of therapy were employed: complete surgical resection, radiation therapy alone, and radiation therapy after endoscopic removal of tumor tissue. Superior results were obtained in the group with adenoid cystic carcinoma, when complete resection was possible. Significant survival and palliation of sepsis was achieved with subtotal resection. The mucoepidermoid carcinomas in this series were classified on the basis of histologic differentiation. Mucoepidermoid carcinoma of Grade 1 was managed by conservative pulmonary resection. Mucoepidermoid carcinoma of Grades 2 and 3 showed a greater propensity for malignancy. Widespread dissemination caused death with unresectable high-grade mucoepidermoid carcinomas of Grades 2 and 3.", "contents": "Adenoid cystic carcinoma (cylindroma) and mucoepidermoid carcinoma of the bronchus. Factors affecting survival. A review was made of the presentation, treatment, and follow-up of 20 patients with adenoid cystic carcinoma and 12 patients with mucoepidermoid carcinoma of the bronchus who were seen at the Mayo Clinic during the 50 year period 1927 through 1977. Three forms of therapy were employed: complete surgical resection, radiation therapy alone, and radiation therapy after endoscopic removal of tumor tissue. Superior results were obtained in the group with adenoid cystic carcinoma, when complete resection was possible. Significant survival and palliation of sepsis was achieved with subtotal resection. The mucoepidermoid carcinomas in this series were classified on the basis of histologic differentiation. Mucoepidermoid carcinoma of Grade 1 was managed by conservative pulmonary resection. Mucoepidermoid carcinoma of Grades 2 and 3 showed a greater propensity for malignancy. Widespread dissemination caused death with unresectable high-grade mucoepidermoid carcinomas of Grades 2 and 3."}
{"id": "PMID:210335", "title": "Lack of effect of halothane on E, EA, and EAC rosette formation and cyclic AMP level of human lymphocytes.", "content": "The effect of halothane on rosette formation and cyclic adenosine monophosphate (cyclic AMP) level of human lymphocytes was investigated. A 4- or 24-hour incubation with 2% halothane had no significant effect on \"early\" or \"late\" E, EA and EAC rosette formation or intracellular cyclic AMP levels of human lymphocytes whereas cytochalasin B, which affects microfilament action, reversibly inhibited both E and EA but not EAC rosette formation. It is suggested that halothane in clinical concentrations neither disturbs the function of microfilaments, essential for E and EA rosette formation, nor affects the metabolism of cyclic AMP in unstimulated human lymphocytes.", "contents": "Lack of effect of halothane on E, EA, and EAC rosette formation and cyclic AMP level of human lymphocytes. The effect of halothane on rosette formation and cyclic adenosine monophosphate (cyclic AMP) level of human lymphocytes was investigated. A 4- or 24-hour incubation with 2% halothane had no significant effect on \"early\" or \"late\" E, EA and EAC rosette formation or intracellular cyclic AMP levels of human lymphocytes whereas cytochalasin B, which affects microfilament action, reversibly inhibited both E and EA but not EAC rosette formation. It is suggested that halothane in clinical concentrations neither disturbs the function of microfilaments, essential for E and EA rosette formation, nor affects the metabolism of cyclic AMP in unstimulated human lymphocytes."}
{"id": "PMID:210337", "title": "Current principles of dietary therapy of diabetes mellitus.", "content": "\"Diet therapy\" is a term with multiple implications. Current concepts, and the principles upon which they are based, are examined, and an attempt is made to elaborate diet therapy in the context of the pathogenesis of diabetes.", "contents": "Current principles of dietary therapy of diabetes mellitus. \"Diet therapy\" is a term with multiple implications. Current concepts, and the principles upon which they are based, are examined, and an attempt is made to elaborate diet therapy in the context of the pathogenesis of diabetes."}
{"id": "PMID:210340", "title": "[Morphology of nasopharyngeal fibroma (author's transl)].", "content": "Light and electron microscopic investigations of four cases with juvenile nasopharyngeal fibroma revealed the characteristic structures like a fibrous stroma, and inclination to hyalinisation and formation of scar like tissue, a lacunar thin walled vascular component, a high amount of mast cells, and of fibroblasts with different nuclear bodies and particles. The well known electron dense nuclear inclusions were subdivided into three groups of size. The tumor cell nuclei also contained five different types of more or less complex bodies with spherical shape. In addition to the earlier described ultrastructural properties of the tumor the nuclei of the tumorous fibroblasts were found to contain virus like particles measuring 40 to 55 nm in diameter. These particles were aggregated to groups; they were different from chromatin condensations and from perichromatin granules. The structure and size of  the smaller particles was not comparable to that of the electron dense nuclear inclusions regarded as pathognomonic in the nasopharynegal fibroma.", "contents": "[Morphology of nasopharyngeal fibroma (author's transl)]. Light and electron microscopic investigations of four cases with juvenile nasopharyngeal fibroma revealed the characteristic structures like a fibrous stroma, and inclination to hyalinisation and formation of scar like tissue, a lacunar thin walled vascular component, a high amount of mast cells, and of fibroblasts with different nuclear bodies and particles. The well known electron dense nuclear inclusions were subdivided into three groups of size. The tumor cell nuclei also contained five different types of more or less complex bodies with spherical shape. In addition to the earlier described ultrastructural properties of the tumor the nuclei of the tumorous fibroblasts were found to contain virus like particles measuring 40 to 55 nm in diameter. These particles were aggregated to groups; they were different from chromatin condensations and from perichromatin granules. The structure and size of  the smaller particles was not comparable to that of the electron dense nuclear inclusions regarded as pathognomonic in the nasopharynegal fibroma."}
{"id": "PMID:210341", "title": "[Intravascular coagulation fibrinolysis syndrome (ICF) in patients with epipharyngeal juvenile angiofibroma (author's transl)].", "content": "In two patients with epipharyngeal juvenile angiofibroma we could find coagulation disorders in the sense of the disseminated intravascular coagulation fibrinolysis syndrome (IFC), which was clinically latent before, but became manifest during or after surgery. The author tries to explain the mechanism of its development.", "contents": "[Intravascular coagulation fibrinolysis syndrome (ICF) in patients with epipharyngeal juvenile angiofibroma (author's transl)]. In two patients with epipharyngeal juvenile angiofibroma we could find coagulation disorders in the sense of the disseminated intravascular coagulation fibrinolysis syndrome (IFC), which was clinically latent before, but became manifest during or after surgery. The author tries to explain the mechanism of its development."}
{"id": "PMID:210342", "title": "[Biochemical-immunological comparison of the lymphoid cells of tonsils and adenoids (author's transl)].", "content": "We compared human lymphoid cells isolated from faucial and palatine tonsils by means of 9 different biochemical-immunological parameters. The cell populations were identical in all values. Evidence as to the biological equivalence of the tissues is disclosed.", "contents": "[Biochemical-immunological comparison of the lymphoid cells of tonsils and adenoids (author's transl)]. We compared human lymphoid cells isolated from faucial and palatine tonsils by means of 9 different biochemical-immunological parameters. The cell populations were identical in all values. Evidence as to the biological equivalence of the tissues is disclosed."}
{"id": "PMID:210343", "title": "[Rare causes for epistaxis (author's transl)].", "content": "Rare causes for nosebleeding are different benigne and malignant tumors of the nose and aneurism of the internal carotid artery. Two cases of rupture of an aneurism of the internal carotid artery are reported. One case with a hemangioma of the nasolacrimal duct and the problematic therapy of epistaxis are discussed in cases with Osler's disease.", "contents": "[Rare causes for epistaxis (author's transl)]. Rare causes for nosebleeding are different benigne and malignant tumors of the nose and aneurism of the internal carotid artery. Two cases of rupture of an aneurism of the internal carotid artery are reported. One case with a hemangioma of the nasolacrimal duct and the problematic therapy of epistaxis are discussed in cases with Osler's disease."}
{"id": "PMID:210347", "title": "Rehabilitation of schizophrenics in a developing country (five years of Fountain House, Lahore, Pakistan).", "content": "Facilities for psychiatric treatment in Pakistan are extremely limited. While efforts are in the offing for the extension of Mental Health Services by the Government, a voluntary organization has been running a rehabilitation centre for the mentally ill in Lahore, called Fountain House, since 1971. An important aspect of this pioneer venture is the collaborative links with Fountain House, New York. The results of follow-up studies conducted over a period of 4 years show that programmes and ideas developed in one country can be profitably utilized in another country.", "contents": "Rehabilitation of schizophrenics in a developing country (five years of Fountain House, Lahore, Pakistan). Facilities for psychiatric treatment in Pakistan are extremely limited. While efforts are in the offing for the extension of Mental Health Services by the Government, a voluntary organization has been running a rehabilitation centre for the mentally ill in Lahore, called Fountain House, since 1971. An important aspect of this pioneer venture is the collaborative links with Fountain House, New York. The results of follow-up studies conducted over a period of 4 years show that programmes and ideas developed in one country can be profitably utilized in another country."}
{"id": "PMID:210349", "title": "An effect of corticosteroids and 100% oxygen on aryl hydrocarbon hydroxylase, cytochrome-c reductase, and free radical formation by rat lung microsomes.", "content": "Activity of aryl hydrocarbon hydroxylase (AHH), cytochrome c-reductase, and NADPH oxidase, and epinephrine oxidation to adrenochrome were determined in lung microsomes from intact, adrenalectomized, and adrenalectomized cortisol-treated female rats under ambient and hyperoxic conditions. Microsomal adrenochrome formation, which is initiated by superoxide anion or other free radicals, was increased by adrenalectomy and decreased by cortisol treatment. Exposure of animals to 100% oxygen caused a further increase in adrenochrome formation. NADPH-cytochrome c-reductase and AHH activities were increased in incubations of microsomes from animals which had received cortisol in vivo while adrenalectomy led to decreases activity. NADPH oxidase activity was increased by cortisol in lung microsomes in the presence of either epinephrine or cytochrome c. Epinephrine conversion to adrenochrome in the presence of lung microsomes was blocked by SOD, but NADPH-cytrochrome c-reductase and AHH activity were unaffected.", "contents": "An effect of corticosteroids and 100% oxygen on aryl hydrocarbon hydroxylase, cytochrome-c reductase, and free radical formation by rat lung microsomes. Activity of aryl hydrocarbon hydroxylase (AHH), cytochrome c-reductase, and NADPH oxidase, and epinephrine oxidation to adrenochrome were determined in lung microsomes from intact, adrenalectomized, and adrenalectomized cortisol-treated female rats under ambient and hyperoxic conditions. Microsomal adrenochrome formation, which is initiated by superoxide anion or other free radicals, was increased by adrenalectomy and decreased by cortisol treatment. Exposure of animals to 100% oxygen caused a further increase in adrenochrome formation. NADPH-cytochrome c-reductase and AHH activities were increased in incubations of microsomes from animals which had received cortisol in vivo while adrenalectomy led to decreases activity. NADPH oxidase activity was increased by cortisol in lung microsomes in the presence of either epinephrine or cytochrome c. Epinephrine conversion to adrenochrome in the presence of lung microsomes was blocked by SOD, but NADPH-cytrochrome c-reductase and AHH activity were unaffected."}
{"id": "PMID:210350", "title": "Effect of obesity on the relationship between very low density lipoprotein production rate and plasma triglyceride concentration in normal and hypertriglyceridemic subjects.", "content": "The effect of obesity on the relationship between very low density lipoprotein (VLDL)-triglyceride (TG) production rate and concentration was studied in 80 subjects whose TG concentrations ranged from 41-1315 mg/100 ml and whose relative weight varied from 0.74-1.46. There was a positive correlation between VLDL-TG production rate and plasma TG concentration in all 80 patients (r = 0.78), which was highly statistically significant (p less than 0.001). Both male and female subjects were subdivided into quartiles on the basis of relative weight; the relationship between VLDL-TG production rate and plasma TG concentration was found to be comparable in all subgroups. These observations suggest that moderate degrees of obesity do not affect VLDL-TG kinetics in patients whose plasma TG levels vary over an extremely wide range.", "contents": "Effect of obesity on the relationship between very low density lipoprotein production rate and plasma triglyceride concentration in normal and hypertriglyceridemic subjects. The effect of obesity on the relationship between very low density lipoprotein (VLDL)-triglyceride (TG) production rate and concentration was studied in 80 subjects whose TG concentrations ranged from 41-1315 mg/100 ml and whose relative weight varied from 0.74-1.46. There was a positive correlation between VLDL-TG production rate and plasma TG concentration in all 80 patients (r = 0.78), which was highly statistically significant (p less than 0.001). Both male and female subjects were subdivided into quartiles on the basis of relative weight; the relationship between VLDL-TG production rate and plasma TG concentration was found to be comparable in all subgroups. These observations suggest that moderate degrees of obesity do not affect VLDL-TG kinetics in patients whose plasma TG levels vary over an extremely wide range."}
{"id": "PMID:210351", "title": "Impaired very low density lipoprotein and triglyceride removal in broad beta disease: comparison with endogenous hypertriglyceridemia.", "content": "The removal rate of apoprotein-B (apo B) in very low density lipoprotein (VLDL) was decreased in individuals with broad beta disease when compared with endogenous hypertriglyceridemia. Following the injection of 125I-VLDL isolated from individuals with endogenous hypertriglyceridemia, both VLDL apo B fractional catabolic rate (0.058 +/- 0.029 hr-1) and VLDL apo-B turnover rate (0.300 +/- 0.070 mg/kg/hr) were lower in broad beta disease than in endogenous hypertriglyceridemia (fractional catabolic rate 0.112 +/- 0.046, p less than .05; turnover rate 0.640 +/- 0.199, p less than .005) despite equivalent plasma concentrations of VLDL-apo-B. Furthermore, conversion of VLDL apo-B to LDL was impaired in broad beta disease relative to endogenous hypertriglyceridemia. Differences in the kinetics of lipoprotein lipase-related triglyceride removal during a maximal heparin infusion were also demonstrated between these two disorders. These differences suggest an abnormality in the interaction of lipoprotein lipase with the lipoproteins of unusual composition in broad beta disease. This is further supported by the normalization of lipoprotein composition in broad beta disease by estrogen therapy, with a simultaneous change in the kinetics of lipoprotein lipase-related triglyceride removal towards those seen in endogenous hypertriglyceridemia.", "contents": "Impaired very low density lipoprotein and triglyceride removal in broad beta disease: comparison with endogenous hypertriglyceridemia. The removal rate of apoprotein-B (apo B) in very low density lipoprotein (VLDL) was decreased in individuals with broad beta disease when compared with endogenous hypertriglyceridemia. Following the injection of 125I-VLDL isolated from individuals with endogenous hypertriglyceridemia, both VLDL apo B fractional catabolic rate (0.058 +/- 0.029 hr-1) and VLDL apo-B turnover rate (0.300 +/- 0.070 mg/kg/hr) were lower in broad beta disease than in endogenous hypertriglyceridemia (fractional catabolic rate 0.112 +/- 0.046, p less than .05; turnover rate 0.640 +/- 0.199, p less than .005) despite equivalent plasma concentrations of VLDL-apo-B. Furthermore, conversion of VLDL apo-B to LDL was impaired in broad beta disease relative to endogenous hypertriglyceridemia. Differences in the kinetics of lipoprotein lipase-related triglyceride removal during a maximal heparin infusion were also demonstrated between these two disorders. These differences suggest an abnormality in the interaction of lipoprotein lipase with the lipoproteins of unusual composition in broad beta disease. This is further supported by the normalization of lipoprotein composition in broad beta disease by estrogen therapy, with a simultaneous change in the kinetics of lipoprotein lipase-related triglyceride removal towards those seen in endogenous hypertriglyceridemia."}
{"id": "PMID:210352", "title": "Pathophysiology of lipoprotein transport.", "content": "A system for classification of genetic and acquired forms of hyperlipidemia in humans based on lipoprotein physiology is described. Most hyperlipidemia can be accounted for by defects in one of four sites of physiologic regulation: (1) triglyceride-rich lipoprotein production, (2) lipoprotein lipase-mediated triglyceride catabolism, (3) remnant lipoprotein catabolism, and (4) extrahepatic cholesterol-rich lipoprotein catabolism.", "contents": "Pathophysiology of lipoprotein transport. A system for classification of genetic and acquired forms of hyperlipidemia in humans based on lipoprotein physiology is described. Most hyperlipidemia can be accounted for by defects in one of four sites of physiologic regulation: (1) triglyceride-rich lipoprotein production, (2) lipoprotein lipase-mediated triglyceride catabolism, (3) remnant lipoprotein catabolism, and (4) extrahepatic cholesterol-rich lipoprotein catabolism."}
{"id": "PMID:210363", "title": "Insulinoma: poor recognition of clinical features is the major problem in diagnosis.", "content": "Traditionally it is taught that hypoglycaemia may cause a clinical picture which mimics a variety of neurological and psychiatric disorders. Yet patients with insulinoma continue to baffle many medical specialists, who presumably are not sufficiently aware of the clinical features of hypoglycaemia. After examining medical records of seventeen patients, diagnosed as suffering from \"insulinoma\" in major Melbourne hospitals from 1971 to 1976, it was evident that these patients frequently undergo extensive investigations for supposed neurological disorders, the correct diagnosis being missed until they develop catastrophic symptoms. Of these seventeen patients, the diagnosis was made with reasonable speed in only six cases, while eight patients were initially discharged from hospital with a completely erroneous diagnosis. It seems likely that a number of patients with insulinoma, whose symptoms are less dramatic than those reported here, are being mistakenly treated as having epileptiform or psychiatric disorders.", "contents": "Insulinoma: poor recognition of clinical features is the major problem in diagnosis. Traditionally it is taught that hypoglycaemia may cause a clinical picture which mimics a variety of neurological and psychiatric disorders. Yet patients with insulinoma continue to baffle many medical specialists, who presumably are not sufficiently aware of the clinical features of hypoglycaemia. After examining medical records of seventeen patients, diagnosed as suffering from \"insulinoma\" in major Melbourne hospitals from 1971 to 1976, it was evident that these patients frequently undergo extensive investigations for supposed neurological disorders, the correct diagnosis being missed until they develop catastrophic symptoms. Of these seventeen patients, the diagnosis was made with reasonable speed in only six cases, while eight patients were initially discharged from hospital with a completely erroneous diagnosis. It seems likely that a number of patients with insulinoma, whose symptoms are less dramatic than those reported here, are being mistakenly treated as having epileptiform or psychiatric disorders."}
{"id": "PMID:210365", "title": "[Prolyl hydroxylase activity in liver specimens in chronic liver diseases (author's transl)].", "content": "100 patients were laparoscopied, liver tissue specimens taken from atypically altered areas. Prolyl hydroxylase was determined in the specimen, in parallel tissue was examined by light microscope. 8 groups of patients could be differentiated: Patients 1. with active, 2, with inactive cirrhosis, 3. with fatty infiltrations, 4. with fatty infiltration and mesenchymal reaction, 5. with aggressive, 6. with persistent, 7. with reactive hepatitis, 8. patients without histological changes. In the case of connective tissue increase in the liver prolyl hydroxylase activities were statistically significant above normal. In addition, there was a statistically significant difference between the enzyme activities of each group. A correlation could be found between prolyl hydroxylase activity and morphologically estimated connective tissue formation, but not the serum enzyme activities usually determined in liver diseases. Therefore, could be concluded that prolyl hydroxylase activity is an index of actual collagen biosynthesis in chronic liver diseases.", "contents": "[Prolyl hydroxylase activity in liver specimens in chronic liver diseases (author's transl)]. 100 patients were laparoscopied, liver tissue specimens taken from atypically altered areas. Prolyl hydroxylase was determined in the specimen, in parallel tissue was examined by light microscope. 8 groups of patients could be differentiated: Patients 1. with active, 2, with inactive cirrhosis, 3. with fatty infiltrations, 4. with fatty infiltration and mesenchymal reaction, 5. with aggressive, 6. with persistent, 7. with reactive hepatitis, 8. patients without histological changes. In the case of connective tissue increase in the liver prolyl hydroxylase activities were statistically significant above normal. In addition, there was a statistically significant difference between the enzyme activities of each group. A correlation could be found between prolyl hydroxylase activity and morphologically estimated connective tissue formation, but not the serum enzyme activities usually determined in liver diseases. Therefore, could be concluded that prolyl hydroxylase activity is an index of actual collagen biosynthesis in chronic liver diseases."}
{"id": "PMID:210362", "title": "\"Twitch box\": a new device to monitor neuromuscular blockade.", "content": "It is proposed that this \"twitch box\" be used whenever monitoring of neuromuscular transmission is indicated, since it is simple to use under clinical conditions, does not require critical placement or adjustment of the hand, produces quantitative information comparable to the force transducer, and is safe.", "contents": "\"Twitch box\": a new device to monitor neuromuscular blockade. It is proposed that this \"twitch box\" be used whenever monitoring of neuromuscular transmission is indicated, since it is simple to use under clinical conditions, does not require critical placement or adjustment of the hand, produces quantitative information comparable to the force transducer, and is safe."}
{"id": "PMID:210366", "title": "Electron paramagnetic resonance investigation of high-spin iron (III) in cancer.", "content": "The concentration of iron (III)-transferrin (IT) in whole blood and serum, along with another high-spin (five unpaired electrons) iron complex (probably IT) accumulated by tumor tissue, was investigated by electron paramagnetic resonance (EPR) spectroscopy during the development of Murphy-Sturm rat lymphosarcoma. The observed changes in concentration (microgram/ml) of IT in sera/blood were generally complementary to those from tissue and the character of the modifications suggested the existence of three distinct phases of systemic response to the implantation: (1) an initial response, evidenced by a sharp reduction in serum IT and somewhat high tissue-IT concentration (microgram/g); (2) a period in which the tumor is (2) a period in which the tumor is becoming established, indicated by relatively constant tissue IT levels and near normal serum IT; and (3) the onset of rapid cell multiplication, characterized by increased total tissue-IT accumulation that rises to above 200% of normal available serum iron, increasing tissue-IT concentration, and rapidly declining serum-IT concentration. The results suggest that, in the face of an implanted tumor there are two detectable abnormal serum-IT responses: (1) an initial change, probably due to systemic blockage of iron reutilization; and (2) extraction of IT from serum by multiplying tumor cells, which is probably a major contributor to reduced serum-IT levels and ultimately anemia.", "contents": "Electron paramagnetic resonance investigation of high-spin iron (III) in cancer. The concentration of iron (III)-transferrin (IT) in whole blood and serum, along with another high-spin (five unpaired electrons) iron complex (probably IT) accumulated by tumor tissue, was investigated by electron paramagnetic resonance (EPR) spectroscopy during the development of Murphy-Sturm rat lymphosarcoma. The observed changes in concentration (microgram/ml) of IT in sera/blood were generally complementary to those from tissue and the character of the modifications suggested the existence of three distinct phases of systemic response to the implantation: (1) an initial response, evidenced by a sharp reduction in serum IT and somewhat high tissue-IT concentration (microgram/g); (2) a period in which the tumor is (2) a period in which the tumor is becoming established, indicated by relatively constant tissue IT levels and near normal serum IT; and (3) the onset of rapid cell multiplication, characterized by increased total tissue-IT accumulation that rises to above 200% of normal available serum iron, increasing tissue-IT concentration, and rapidly declining serum-IT concentration. The results suggest that, in the face of an implanted tumor there are two detectable abnormal serum-IT responses: (1) an initial change, probably due to systemic blockage of iron reutilization; and (2) extraction of IT from serum by multiplying tumor cells, which is probably a major contributor to reduced serum-IT levels and ultimately anemia."}
{"id": "PMID:210371", "title": "Location of the cleavage sites on the SV 40 DNA map produced by the restriction endonucleases Pst 1 and Bam 1.", "content": "Restriction endonucleases from Providencia stuartii (Pst 1) and Bacillus amyloliquefaciens H (Bam 1) cleave SV 40 DNA at two and one specific sites, respectively. Using EcoRI and Hind III endonuclease restriction sites as reference, the two Pst I sites were mapped at 0.050; 0.265 and the Bam I site was mapped at 0.170 of the genome length, clockwise, from the single EcoRI cleavage site.", "contents": "Location of the cleavage sites on the SV 40 DNA map produced by the restriction endonucleases Pst 1 and Bam 1. Restriction endonucleases from Providencia stuartii (Pst 1) and Bacillus amyloliquefaciens H (Bam 1) cleave SV 40 DNA at two and one specific sites, respectively. Using EcoRI and Hind III endonuclease restriction sites as reference, the two Pst I sites were mapped at 0.050; 0.265 and the Bam I site was mapped at 0.170 of the genome length, clockwise, from the single EcoRI cleavage site."}
{"id": "PMID:210375", "title": "[Clofibrate in type IIa hyperlipoproteinemia. Reduction of apolipoprotein B (author's transl)].", "content": "After changing over from the usual eating habits to a \"reasonable\" restricted diet rich in polyene saturated fats and saturated fatty acids, additional treatment with 1 g clofibrate twice daily produces a significant reduction of concentration of total cholesterol and Apo B by about 24% in the serum of patients with Type IIa hyperlipoproteinemia after 2 weeks. In contrast to this the serum concentration of triglycerides and phospholipids shows an insignificant tendency to fall during the whole duration of the trial. The results suggest that the additional cholesterol reducing action of clofibrate in patients with hyperlipoproteinemia Type IIa who have already been treated by diet is mainly achieved by the reduction of LDL-cholesterol, the atherogenic properties of which are well known.", "contents": "[Clofibrate in type IIa hyperlipoproteinemia. Reduction of apolipoprotein B (author's transl)]. After changing over from the usual eating habits to a \"reasonable\" restricted diet rich in polyene saturated fats and saturated fatty acids, additional treatment with 1 g clofibrate twice daily produces a significant reduction of concentration of total cholesterol and Apo B by about 24% in the serum of patients with Type IIa hyperlipoproteinemia after 2 weeks. In contrast to this the serum concentration of triglycerides and phospholipids shows an insignificant tendency to fall during the whole duration of the trial. The results suggest that the additional cholesterol reducing action of clofibrate in patients with hyperlipoproteinemia Type IIa who have already been treated by diet is mainly achieved by the reduction of LDL-cholesterol, the atherogenic properties of which are well known."}
{"id": "PMID:210376", "title": "[Cardinal symptom: uterine hemorrhage (author's transl)].", "content": "Uterine hemorrhages are dependent on the vascular architecture of the endometrium: the endometrial spiral arteries supply sectors strictly separated from each other at intervals of about 1.4 mm. Their function is so closely coupled with the endocrine regulation of the cycle that the presence of hormonal receptors in the vessel wall must be assumed. Menstrual bleeding is an instructive example of morphologically detectable endocrine controlled processes. Endometrial hemorrhage in adenocarcinoma appears early, but it is not an early symptom because the surface epithelium remains intact at first. The diagnosis of precancerous changes in the endometrium (adenomatous hyperplasia--carcinoma in situ) is based on the condition of the surface epithelial cells. Extrauterine pregnancies, miscarriages and trophoblastic diseases are usually diagnosed from the uterine hemorrhage. The quality of the hemorrhage in early pregnancy has less diagnostic importance than, for example, in dyshormonal hemorrhagic disorders.", "contents": "[Cardinal symptom: uterine hemorrhage (author's transl)]. Uterine hemorrhages are dependent on the vascular architecture of the endometrium: the endometrial spiral arteries supply sectors strictly separated from each other at intervals of about 1.4 mm. Their function is so closely coupled with the endocrine regulation of the cycle that the presence of hormonal receptors in the vessel wall must be assumed. Menstrual bleeding is an instructive example of morphologically detectable endocrine controlled processes. Endometrial hemorrhage in adenocarcinoma appears early, but it is not an early symptom because the surface epithelium remains intact at first. The diagnosis of precancerous changes in the endometrium (adenomatous hyperplasia--carcinoma in situ) is based on the condition of the surface epithelial cells. Extrauterine pregnancies, miscarriages and trophoblastic diseases are usually diagnosed from the uterine hemorrhage. The quality of the hemorrhage in early pregnancy has less diagnostic importance than, for example, in dyshormonal hemorrhagic disorders."}
{"id": "PMID:210377", "title": "Platelet function in essential thrombocythemia. Decreased epinephrine responsiveness associated with a deficiency of platelet alpha-adrenergic receptors.", "content": "Platelets from two patients with essential thrombocythemia failed to aggregate or release serotonin in response to concentrations of epinephrine that aggregated platelets from normal controls. Therefore, we studied their alpha-adrenergic receptors, using 3H-dihydroergocryptine (3H-DHE), an alpha-adrenergic antagonist. These platelets contained an average (mean +/- S.E.) of 210 +/- 18 and 227 +/- 27 3H-DHE binding sites per platelet--less than half that found on control platelets, 464 +/- 37 (P less than 0.01). In contrast, platelets from two other patients with essential thrombocythemia responded to epinephrine and contained a normal number of 3H-DHE sites. Platelets in essential thrombocythemia demonstrated normal kinetics of 3H-DHE binding and normal affinities for 3H-DHE and for epinephrine. When control platelets were preincubated with a half-saturating concentration of 3H-DHE, there was a diminution of epinephrine-induced platelet function comparable to that seen in essential thrombocythemia. Thus, a deficiency of alpha-adrenergic receptors may account for diminished functional responsiveness of platelets to epinephrine in some patients with essential thrombocythemia.", "contents": "Platelet function in essential thrombocythemia. Decreased epinephrine responsiveness associated with a deficiency of platelet alpha-adrenergic receptors. Platelets from two patients with essential thrombocythemia failed to aggregate or release serotonin in response to concentrations of epinephrine that aggregated platelets from normal controls. Therefore, we studied their alpha-adrenergic receptors, using 3H-dihydroergocryptine (3H-DHE), an alpha-adrenergic antagonist. These platelets contained an average (mean +/- S.E.) of 210 +/- 18 and 227 +/- 27 3H-DHE binding sites per platelet--less than half that found on control platelets, 464 +/- 37 (P less than 0.01). In contrast, platelets from two other patients with essential thrombocythemia responded to epinephrine and contained a normal number of 3H-DHE sites. Platelets in essential thrombocythemia demonstrated normal kinetics of 3H-DHE binding and normal affinities for 3H-DHE and for epinephrine. When control platelets were preincubated with a half-saturating concentration of 3H-DHE, there was a diminution of epinephrine-induced platelet function comparable to that seen in essential thrombocythemia. Thus, a deficiency of alpha-adrenergic receptors may account for diminished functional responsiveness of platelets to epinephrine in some patients with essential thrombocythemia."}
{"id": "PMID:210378", "title": "Tangier disease: one explanation of lipid storage.", "content": "Normal high-density lipoproteins are absent from plasma in Tangier disease, and the disorder is characterized by accumulation of cholesteryl esters in several tissues, particularly those of the reticuloendothelial system. Electron microscopy of the abnormal high-density lipoproteins in the plasma of three patients with Tangier diseases revealed large (68-nm), flattened, translucent particles in all cases. These particles were most abundant in the plasma of the splenectomized patient. Restriction of dietary fat eliminated or drastically reduced the numbers of these particles among the Tangier high-density lipoproteins. Thus abnormal products of chylomicron metabolism that appear to occur in plasma in this disorder may be targets for phagocytosis and may be at least one source of the cholesteryl esters that accumulate in reticuloendothelial tissues in Tangier disease.", "contents": "Tangier disease: one explanation of lipid storage. Normal high-density lipoproteins are absent from plasma in Tangier disease, and the disorder is characterized by accumulation of cholesteryl esters in several tissues, particularly those of the reticuloendothelial system. Electron microscopy of the abnormal high-density lipoproteins in the plasma of three patients with Tangier diseases revealed large (68-nm), flattened, translucent particles in all cases. These particles were most abundant in the plasma of the splenectomized patient. Restriction of dietary fat eliminated or drastically reduced the numbers of these particles among the Tangier high-density lipoproteins. Thus abnormal products of chylomicron metabolism that appear to occur in plasma in this disorder may be targets for phagocytosis and may be at least one source of the cholesteryl esters that accumulate in reticuloendothelial tissues in Tangier disease."}
{"id": "PMID:210379", "title": "Antibiotic irrigation and catheter-associated urinary-tract infections.", "content": "To investigate the efficacy of antibiotic irrigation in preventing catheter-associated urinarytract infection, we carried out a randomized controlled trial of a neomycin-polymyxin irrigant administered through closed urinary catheters. Eighteen of 98 (18 per cent) of the patients not given irrigation became infected, as compared with 14 of 89 (16 per cent) of those given irrigation, yielding a mean daily incidence of 5 per cent in each group. The distribution of organisms and their antibiotic sensitivities differed in the two groups, the organisms from the patients with irrigation being more resistant. Disconnections of the catheter junctions were associated with high rates of infection. The rate of disconnections of the junctions in the group given irrigation was almost twice that of the control group because of the presence of the extra junction on overall infection rate represents the result of two opposing phenomena: the increased entry of organisms and the suppression of a portion of them.", "contents": "Antibiotic irrigation and catheter-associated urinary-tract infections. To investigate the efficacy of antibiotic irrigation in preventing catheter-associated urinarytract infection, we carried out a randomized controlled trial of a neomycin-polymyxin irrigant administered through closed urinary catheters. Eighteen of 98 (18 per cent) of the patients not given irrigation became infected, as compared with 14 of 89 (16 per cent) of those given irrigation, yielding a mean daily incidence of 5 per cent in each group. The distribution of organisms and their antibiotic sensitivities differed in the two groups, the organisms from the patients with irrigation being more resistant. Disconnections of the catheter junctions were associated with high rates of infection. The rate of disconnections of the junctions in the group given irrigation was almost twice that of the control group because of the presence of the extra junction on overall infection rate represents the result of two opposing phenomena: the increased entry of organisms and the suppression of a portion of them."}
{"id": "PMID:210383", "title": "Response of 1alpha,25-dihydroxyvitamin D3 to hypocalcemia in human subjects.", "content": "We determined the response of 1alpha,25-dihydroxyvitamin D3 after mithramycin-induced hypocalcemia in eight subjects with polyostotic Paget's disease of bone. Thirty-six hours after infusion of mithramycin (25 microgram per kilogram), the average calcium declined from 9.9 +/- 0.14 (S.E.M.) to 8.0 +/- 0.19 mg per deciliter (P less than 0.005). Serum parathyroid hormone increased from 122 +/- 6 to 226 +/- 36 microliter eq per milliliter (P less than 0.05), serum phosphate decreased from 3.8 +/- 0.11 to 2.9 +/- 0.14 mg per deciliter (P less than 0.005), and urinary cyclic 3,5'-adenosine monophosphate increased from 4.6 +/- 0.35 to 7.5 +/- 0.80 mumol per gram of creatinine (P less than 0.005). Serum 1alpha25-dihydroxyvitamin D3 rose from 98 +/- 12 to 332 +/- 61 pM (P less than 0.05), the increase following the changes in parathyroid hormone and phosphate by 12 to 24 hours. When this lag period was taken into account, there was a significant relation (P less than 0.01) between the increase in 1alpha,25-dihydroxyvitamin D3 and changes in parathyroid hormone (correlation coefficient, r = +0.91) and phosphate (r = -0.96). The relatively rapid response of 1alpha,25-dihydroxyvitamin D3 to hypocalcemia occurs with a time course consistent with regulation by parathyroid hormone and phosphate.", "contents": "Response of 1alpha,25-dihydroxyvitamin D3 to hypocalcemia in human subjects. We determined the response of 1alpha,25-dihydroxyvitamin D3 after mithramycin-induced hypocalcemia in eight subjects with polyostotic Paget's disease of bone. Thirty-six hours after infusion of mithramycin (25 microgram per kilogram), the average calcium declined from 9.9 +/- 0.14 (S.E.M.) to 8.0 +/- 0.19 mg per deciliter (P less than 0.005). Serum parathyroid hormone increased from 122 +/- 6 to 226 +/- 36 microliter eq per milliliter (P less than 0.05), serum phosphate decreased from 3.8 +/- 0.11 to 2.9 +/- 0.14 mg per deciliter (P less than 0.005), and urinary cyclic 3,5'-adenosine monophosphate increased from 4.6 +/- 0.35 to 7.5 +/- 0.80 mumol per gram of creatinine (P less than 0.005). Serum 1alpha25-dihydroxyvitamin D3 rose from 98 +/- 12 to 332 +/- 61 pM (P less than 0.05), the increase following the changes in parathyroid hormone and phosphate by 12 to 24 hours. When this lag period was taken into account, there was a significant relation (P less than 0.01) between the increase in 1alpha,25-dihydroxyvitamin D3 and changes in parathyroid hormone (correlation coefficient, r = +0.91) and phosphate (r = -0.96). The relatively rapid response of 1alpha,25-dihydroxyvitamin D3 to hypocalcemia occurs with a time course consistent with regulation by parathyroid hormone and phosphate."}
{"id": "PMID:210386", "title": "High incidence area of cattle cancer with a possible interaction between an environmental carcinogen and a papilloma virus.", "content": "Cattle in upland areas of Scotland and northern England are substantially more prone to alimentary cancer than those of the immediately neighbouring lowlands, and epidemiological evidence implicates a combination of papilloma virus and bracken in the aetiology of the disease. Here Professor Jarrett outlines the circumstantial case against these agents and discusses its implications.", "contents": "High incidence area of cattle cancer with a possible interaction between an environmental carcinogen and a papilloma virus. Cattle in upland areas of Scotland and northern England are substantially more prone to alimentary cancer than those of the immediately neighbouring lowlands, and epidemiological evidence implicates a combination of papilloma virus and bracken in the aetiology of the disease. Here Professor Jarrett outlines the circumstantial case against these agents and discusses its implications."}
{"id": "PMID:210392", "title": "Epidemiological evidence for causal relationship between Epstein-Barr virus and Burkitt's lymphoma from Ugandan prospective study.", "content": "Results from a prospective sero-epidemiological study initiated in Uganda in 1971 indicate that children with high antibody titres to Epstein-Barr virus structural antigens are at high risk of developing Burkitt's lymphoma. These findings strongly support a causal relationship between the Epstein-Barr virus and Burkitt's lymphoma but suggest that the oncogenic potential of the virus is realised only in exceptional circumstances.", "contents": "Epidemiological evidence for causal relationship between Epstein-Barr virus and Burkitt's lymphoma from Ugandan prospective study. Results from a prospective sero-epidemiological study initiated in Uganda in 1971 indicate that children with high antibody titres to Epstein-Barr virus structural antigens are at high risk of developing Burkitt's lymphoma. These findings strongly support a causal relationship between the Epstein-Barr virus and Burkitt's lymphoma but suggest that the oncogenic potential of the virus is realised only in exceptional circumstances."}
{"id": "PMID:210395", "title": "Transformation by concanavalin A of the response of molluscan neurones to L-glutamate.", "content": "Concanavalin A causes in all Aplysia and Helix neurones a depolarising response to L-glutamate. The Con A-induced glutamate response is pharmacologically distinct from the three cell-specific glutamate responses (two inhibitory, one excitatory) that can be elicited from untreated molluscan neurones. The transformation in glutamate sensitivity brought about by Con A does not seem to be related to the lectin's capacity to produce redistribution of receptor sites in cell membranes.", "contents": "Transformation by concanavalin A of the response of molluscan neurones to L-glutamate. Concanavalin A causes in all Aplysia and Helix neurones a depolarising response to L-glutamate. The Con A-induced glutamate response is pharmacologically distinct from the three cell-specific glutamate responses (two inhibitory, one excitatory) that can be elicited from untreated molluscan neurones. The transformation in glutamate sensitivity brought about by Con A does not seem to be related to the lectin's capacity to produce redistribution of receptor sites in cell membranes."}
{"id": "PMID:210404", "title": "High affinity of carozolol for beta-adrenoceptors coupled to the adenylyl cyclase in ventricular myocardium of kitten and Xenopus laevis.", "content": "Catecholamine-induced stimulation of adenylyl cyclase in ventricular membranes of kitten and Xenopus laevis was antagonized competitively by carazolol. Apparent equilibrium constants ranging between 100-170 pM were estimated for the beta-adrenoceptor-carazolol complex.", "contents": "High affinity of carozolol for beta-adrenoceptors coupled to the adenylyl cyclase in ventricular myocardium of kitten and Xenopus laevis. Catecholamine-induced stimulation of adenylyl cyclase in ventricular membranes of kitten and Xenopus laevis was antagonized competitively by carazolol. Apparent equilibrium constants ranging between 100-170 pM were estimated for the beta-adrenoceptor-carazolol complex."}
{"id": "PMID:210405", "title": "The lack of active bile acid transport in AS-30 D ascites hepatoma cells.", "content": "The uptake of cholic acid as well as taurocholic acid into AS-30 D ascites hepatoma cells showed linearity with respect to incubation concentrations. It has been suggested that these processes can be described as simple diffusion. In further experiments it could be shown that ascites hepatoma cells were unable to conjugate cholic acid. These results may have significance in the phalloidin action on hepatocytes.", "contents": "The lack of active bile acid transport in AS-30 D ascites hepatoma cells. The uptake of cholic acid as well as taurocholic acid into AS-30 D ascites hepatoma cells showed linearity with respect to incubation concentrations. It has been suggested that these processes can be described as simple diffusion. In further experiments it could be shown that ascites hepatoma cells were unable to conjugate cholic acid. These results may have significance in the phalloidin action on hepatocytes."}
{"id": "PMID:210407", "title": "[Convergence of reticulo-, vestibulo- and rubrospinal influences on motor neurons of the cervical region of the cat spinal cord].", "content": "Intracellular recording of synaptic potentials of 93 cervical motoneurons was performed in cats under stimulation of medial longitudinal fasciculus, Deiters vestibular nucleus and red nucleus. Under stimulation of medial longitudinal fasciculus and Deiters nucleus in motoneurons of the forelimb muscles distal groups excitatory reactions were predominant and in motoneurons of proximal extensors inhibitory reactions prevailed. When stimulating the red nucleus excitatory and inhibitory reactions were recorded almost in equal number of cells independently of functional significance of corresponding muscles. Monosynaptic EPSPs were recorded in 1/5 of motoneurons under stimulation of the medial longitudinal fasciculus and only in several cases during stimulation of vestibular and red nuclei. In the other cases stimulation of the structures investigated caused polysynaptic reactions in motoneurons which arose after a series of 2-3 stimuli. In 62% of motoneurons when stimulating different structures under study the reactions were of the same direction. The mutual facilitation of reactions was revealed under stimulation of different inputs. The data obtained show that interaction of influences of the studied structures occurs to a considerable extent at the level of spinal interneurons.", "contents": "[Convergence of reticulo-, vestibulo- and rubrospinal influences on motor neurons of the cervical region of the cat spinal cord]. Intracellular recording of synaptic potentials of 93 cervical motoneurons was performed in cats under stimulation of medial longitudinal fasciculus, Deiters vestibular nucleus and red nucleus. Under stimulation of medial longitudinal fasciculus and Deiters nucleus in motoneurons of the forelimb muscles distal groups excitatory reactions were predominant and in motoneurons of proximal extensors inhibitory reactions prevailed. When stimulating the red nucleus excitatory and inhibitory reactions were recorded almost in equal number of cells independently of functional significance of corresponding muscles. Monosynaptic EPSPs were recorded in 1/5 of motoneurons under stimulation of the medial longitudinal fasciculus and only in several cases during stimulation of vestibular and red nuclei. In the other cases stimulation of the structures investigated caused polysynaptic reactions in motoneurons which arose after a series of 2-3 stimuli. In 62% of motoneurons when stimulating different structures under study the reactions were of the same direction. The mutual facilitation of reactions was revealed under stimulation of different inputs. The data obtained show that interaction of influences of the studied structures occurs to a considerable extent at the level of spinal interneurons."}
{"id": "PMID:210408", "title": "Effect of parathyroid hormone and insulin on extracellular cyclic adenosine-3',5'-monophosphate in patients with benign and malignant breast tumors.", "content": "Basal excretion of cyclic adenosine monophosphate (cAMP) and its basal level in blood plasma in breast cancer (BC) patients and those with fibroadenomatosis did not differ essentially. However, intravenous injection of parathyroid hormone (100 U) and insulin (0.08 U/kg body weight) was followed by a much less rise in urine-cAMP excretion and blood-cAMP levels in BC patients than in benign process in mammary gland. A substantial correlation between changes in plasma cAMP level and the degree of insulin-induced hypoglycemia was not observed. There was a negative correlation between reponse to parathyroid hormone and insulin and body overweight in BC patients. It was suggested that body fat content may influence the peculiarities of metabolism of extracellular cAMP in cancer patients considerably.", "contents": "Effect of parathyroid hormone and insulin on extracellular cyclic adenosine-3',5'-monophosphate in patients with benign and malignant breast tumors. Basal excretion of cyclic adenosine monophosphate (cAMP) and its basal level in blood plasma in breast cancer (BC) patients and those with fibroadenomatosis did not differ essentially. However, intravenous injection of parathyroid hormone (100 U) and insulin (0.08 U/kg body weight) was followed by a much less rise in urine-cAMP excretion and blood-cAMP levels in BC patients than in benign process in mammary gland. A substantial correlation between changes in plasma cAMP level and the degree of insulin-induced hypoglycemia was not observed. There was a negative correlation between reponse to parathyroid hormone and insulin and body overweight in BC patients. It was suggested that body fat content may influence the peculiarities of metabolism of extracellular cAMP in cancer patients considerably."}
{"id": "PMID:210409", "title": "Effect of irradiation on enzyme activities of cyclic AMP system in the neuro- and adenohypophyses.", "content": "The enzyme activities of cyclic AMP system in the neuro- and adenohypophyses were studied, immediately after an irradiation by a single whole body exposure of 1600 R, in an attempt to find whether this intervention causes the changes in the responsiveness of the cyclic AMP regulatory system. In the irradiated rats the neurohypophyses revealed a reduced activity of adenylate cyclase, moderately increased activity of phosphodiesterase and slightly decreased activity of protein kinase, including the value stimulated by cyclic AMP. In the adenohypophyses the irradiation did not cause any significant changes in the enzyme activities of the cyclic AMP system, except of slightly decreased adenylate cyclase activity. The possible relationship of the plasma level of antidiuretic hormone immediately after irradiation and the enzyme activities of cyclic AMP system is discussed.", "contents": "Effect of irradiation on enzyme activities of cyclic AMP system in the neuro- and adenohypophyses. The enzyme activities of cyclic AMP system in the neuro- and adenohypophyses were studied, immediately after an irradiation by a single whole body exposure of 1600 R, in an attempt to find whether this intervention causes the changes in the responsiveness of the cyclic AMP regulatory system. In the irradiated rats the neurohypophyses revealed a reduced activity of adenylate cyclase, moderately increased activity of phosphodiesterase and slightly decreased activity of protein kinase, including the value stimulated by cyclic AMP. In the adenohypophyses the irradiation did not cause any significant changes in the enzyme activities of the cyclic AMP system, except of slightly decreased adenylate cyclase activity. The possible relationship of the plasma level of antidiuretic hormone immediately after irradiation and the enzyme activities of cyclic AMP system is discussed."}
{"id": "PMID:210411", "title": "Dissociation of tubular sites of action of saline, PTH and DbCAMP on renal phosphate reabsorption.", "content": "The effects of saline expansion, parathyroid hormone (PTH) administration and dibutyryl cyclic 3'5'-adenosine monophosphate (DbCAMP) infusion on renal phosphate reabsorption were examined in acutely thyroparathyroidectomized (TPTX), phosphate infused dogs by the recollection micropuncture technique. Saline expansion reduced whole kidney phosphate reabsorption from a mean of 66.1 to 50.4% of filtered load. This response was entirely accounted for by an inhibition of proximal tubular phosphate reabsorption which fell from a mean of 35 to 21% of the filtered phosphate load. Both PTH and DbCAMP produced a fall in whole kidney phosphate reabsorption comparable to saline. However, this effect was the sum of inhibition of both proximal tubular and distal nephron phosphate reabsorption. These studies demonstrate the important role of the distal nephron in modulating urinary phosphate excretion.", "contents": "Dissociation of tubular sites of action of saline, PTH and DbCAMP on renal phosphate reabsorption. The effects of saline expansion, parathyroid hormone (PTH) administration and dibutyryl cyclic 3'5'-adenosine monophosphate (DbCAMP) infusion on renal phosphate reabsorption were examined in acutely thyroparathyroidectomized (TPTX), phosphate infused dogs by the recollection micropuncture technique. Saline expansion reduced whole kidney phosphate reabsorption from a mean of 66.1 to 50.4% of filtered load. This response was entirely accounted for by an inhibition of proximal tubular phosphate reabsorption which fell from a mean of 35 to 21% of the filtered phosphate load. Both PTH and DbCAMP produced a fall in whole kidney phosphate reabsorption comparable to saline. However, this effect was the sum of inhibition of both proximal tubular and distal nephron phosphate reabsorption. These studies demonstrate the important role of the distal nephron in modulating urinary phosphate excretion."}
{"id": "PMID:210412", "title": "Characterization of protein kinases from adrenal medulla. A study of cytosol and nuclear enzymes.", "content": "Since phosphorylation of chromosomal proteins by cyclic AMP-dependent protein kinases (EC 2.7.1.37) enhances template activity of adrenal medulla chromatin (9), we have studied the properties and regulation of protein kinases isolated from chromaffin cell cytosol and nuclei. DEAE-cellulose chromatography revealed three peaks of kinase activity in the nucleus (nPKI, nPKII, nPKIII) and two in the cytosol (cPKI, cPKII). The three nuclear enzymes, as well as cPKII, did not require cyclic AMP to express their catalytic activity. nPKI and nPKIII preferred acidic substrates as PO3-4 acceptors, while nPKII and the cytosol enzymes preferred basic PO3-4 acceptors. Enzyme recombination experiments using protein kinase regulatory subunits from cytosol suggested that cPKII was the catalytic subunit of cPKI. In contrast, the nuclear enzymes were not catalytic subunits of the cyclic AMP-dependent protein kinase in the cytosol (cPKI). Only the cytosol protein kinases could be inhibited by endogenous heat-stable protein kinase inhibitors. The nuclear and cytosol cyclic AMP-independent protein kinases were distinguishable on the basis of their sedimentation constants as well as Mc2+ and Mn2+ requirements.", "contents": "Characterization of protein kinases from adrenal medulla. A study of cytosol and nuclear enzymes. Since phosphorylation of chromosomal proteins by cyclic AMP-dependent protein kinases (EC 2.7.1.37) enhances template activity of adrenal medulla chromatin (9), we have studied the properties and regulation of protein kinases isolated from chromaffin cell cytosol and nuclei. DEAE-cellulose chromatography revealed three peaks of kinase activity in the nucleus (nPKI, nPKII, nPKIII) and two in the cytosol (cPKI, cPKII). The three nuclear enzymes, as well as cPKII, did not require cyclic AMP to express their catalytic activity. nPKI and nPKIII preferred acidic substrates as PO3-4 acceptors, while nPKII and the cytosol enzymes preferred basic PO3-4 acceptors. Enzyme recombination experiments using protein kinase regulatory subunits from cytosol suggested that cPKII was the catalytic subunit of cPKI. In contrast, the nuclear enzymes were not catalytic subunits of the cyclic AMP-dependent protein kinase in the cytosol (cPKI). Only the cytosol protein kinases could be inhibited by endogenous heat-stable protein kinase inhibitors. The nuclear and cytosol cyclic AMP-independent protein kinases were distinguishable on the basis of their sedimentation constants as well as Mc2+ and Mn2+ requirements."}
{"id": "PMID:210414", "title": "[Value of isotope scintigraphy and angiography in the diagnosis of brain neoplasms].", "content": "The results of cerebral angiography and isotope scintigraphy were compared in 50 patients with brain tumours. The usefulness of each method for detection, localization and determination of the size of the tumour was evaluated. The overall detection rate of brain tumours was 92% in the case of angiography and 90% for scintigraphy, the possiblity of localization was 86% and 90% and size determination was 50% and 74% respectively. Scintigraphy often failed in the diagnosis of astrocytomas and tumours situated near the base of the brain, but this method was more reliable in evaluating the site and size of tumours than angiography.", "contents": "[Value of isotope scintigraphy and angiography in the diagnosis of brain neoplasms]. The results of cerebral angiography and isotope scintigraphy were compared in 50 patients with brain tumours. The usefulness of each method for detection, localization and determination of the size of the tumour was evaluated. The overall detection rate of brain tumours was 92% in the case of angiography and 90% for scintigraphy, the possiblity of localization was 86% and 90% and size determination was 50% and 74% respectively. Scintigraphy often failed in the diagnosis of astrocytomas and tumours situated near the base of the brain, but this method was more reliable in evaluating the site and size of tumours than angiography."}
{"id": "PMID:210415", "title": "The pathogenesis and pathway into the central nervous system after intraocular infection of herpes simplex virus type I in rabbits.", "content": "Herpes simplex virus (HSV) type I was injected into the right eye of 18-day-old New Zealand albino rabbits and the animals were killed on the fourth and eighth days after inoculation. Longitudinal section of the optic nerves and chiasma showed that both myelinated axons and neuroglial cells crossed at the chiasma. Semi-serial (1 micrometer) and ultrathin sections showed the presence of HSV in both astrocytes and oligodendrocytes, although no particles were seen in the myelinated axons; the infected cells were confined to the medial side of the right optic nerve. HSV travels centropetally along the optic pathway and slowly spreads laterally by cell-to-cell infection. The virus does not appear to kill the astrocytes and oligodendrocytes, and also does not directly damage the myelin sheath.", "contents": "The pathogenesis and pathway into the central nervous system after intraocular infection of herpes simplex virus type I in rabbits. Herpes simplex virus (HSV) type I was injected into the right eye of 18-day-old New Zealand albino rabbits and the animals were killed on the fourth and eighth days after inoculation. Longitudinal section of the optic nerves and chiasma showed that both myelinated axons and neuroglial cells crossed at the chiasma. Semi-serial (1 micrometer) and ultrathin sections showed the presence of HSV in both astrocytes and oligodendrocytes, although no particles were seen in the myelinated axons; the infected cells were confined to the medial side of the right optic nerve. HSV travels centropetally along the optic pathway and slowly spreads laterally by cell-to-cell infection. The virus does not appear to kill the astrocytes and oligodendrocytes, and also does not directly damage the myelin sheath."}
{"id": "PMID:210416", "title": "Methylprednisolone treatment in patients with brain tumors.", "content": "A study was made in 10 patients with brain tumors of the effect of methylprednisolone sodium succinate (Solu-Medrol) on clinical neurological status, intracranial pressure, and periventricular elastance. Significant clinical improvement and reduction in periventricular elastance both ocurred within 24 hours of starting treatment, whereas intracranaial pressure was not significantly reduced until the 2nd day of therapy.", "contents": "Methylprednisolone treatment in patients with brain tumors. A study was made in 10 patients with brain tumors of the effect of methylprednisolone sodium succinate (Solu-Medrol) on clinical neurological status, intracranial pressure, and periventricular elastance. Significant clinical improvement and reduction in periventricular elastance both ocurred within 24 hours of starting treatment, whereas intracranaial pressure was not significantly reduced until the 2nd day of therapy."}
{"id": "PMID:210417", "title": "Elevations in cerebrospinal fluid norepinephrine during unilateral and bilateral cerebellar stimulation in man.", "content": "Lumbar cerebrospinal fluid (CSF) norepinephrine concentrations determined by radioenzymatic assay in four epileptic patients were significantly higher during either chronic unilateral or bilateral cerebellar stimulation than those determined after a 7-day period without stimulation. The mean CSF norepinephrine levels noted during these two modes of cerebellar stimulation were not significantly different. The percentage of increase in CSF norepinephrine in one patient receiving 200/sec stimulation was 3 times higher than those noted in the three patients undergoing 10/sec stimulation. These evoked alterations in norepinephrine metabolism may relate to the reported modulation of spasticity and cerebral neuronal excitability during chronic cerebellar stimulation. Lumbar CSF cyclic adenosine monophosphate levels determined by radioimmunoassay were not significantly altered by either mode or frequency of cerebellar stimulation.", "contents": "Elevations in cerebrospinal fluid norepinephrine during unilateral and bilateral cerebellar stimulation in man. Lumbar cerebrospinal fluid (CSF) norepinephrine concentrations determined by radioenzymatic assay in four epileptic patients were significantly higher during either chronic unilateral or bilateral cerebellar stimulation than those determined after a 7-day period without stimulation. The mean CSF norepinephrine levels noted during these two modes of cerebellar stimulation were not significantly different. The percentage of increase in CSF norepinephrine in one patient receiving 200/sec stimulation was 3 times higher than those noted in the three patients undergoing 10/sec stimulation. These evoked alterations in norepinephrine metabolism may relate to the reported modulation of spasticity and cerebral neuronal excitability during chronic cerebellar stimulation. Lumbar CSF cyclic adenosine monophosphate levels determined by radioimmunoassay were not significantly altered by either mode or frequency of cerebellar stimulation."}
{"id": "PMID:210422", "title": "Progressive multifocal leukoencephalopathy: failure of response to transfer factor and cytarabine.", "content": "A 57-year-old woman with a 2-year history of neurologic symptoms was shown on brain biopsy to have progressive multifocal leukoencephalopathy. Although cell-mediated immune mechanisms were impaired, no underlying disease was found. The administration of transfer factor enhanced cell-mediated immunity, but the neurologic symptoms did not improve. Separate courses of glucocorticoids and cytarabine were associated with rapid neurologic deterioration.", "contents": "Progressive multifocal leukoencephalopathy: failure of response to transfer factor and cytarabine. A 57-year-old woman with a 2-year history of neurologic symptoms was shown on brain biopsy to have progressive multifocal leukoencephalopathy. Although cell-mediated immune mechanisms were impaired, no underlying disease was found. The administration of transfer factor enhanced cell-mediated immunity, but the neurologic symptoms did not improve. Separate courses of glucocorticoids and cytarabine were associated with rapid neurologic deterioration."}
{"id": "PMID:210423", "title": "Serum factor blocks neuromuscular transmission in myasthenia gravis: electrophysiologic study with intracellular microelectrodes.", "content": "We studied the effects of normal and myasthenic sera on the miniature endplate potential (MEPP) and resting membrane potential (RP) of rat muscle in vitro by conventional intracellular microelectrode techniques. Normal sera had little or no effect on either the amplitude or frequency of MEPP or RP. On the other hand, MEPP amplitude was reduced in each of nine muscles during exposure to myasthenic sera; five of these muscles showed a significant difference, by student's t-test, from the values in a control solution. The half decay time of diminished MEPP remained unchanged. MEPP frequency and RP were not affected by myasthenic sera. The reduced amplitude of the MEPP was almost completely restored when the muscle was washed with a control solution for more than 30 minutes. These observations indicate that myasthenic sera contain factors that bind reversibly with the acetylcholine receptor and reduce postsynaptic responses to acetylcholine.", "contents": "Serum factor blocks neuromuscular transmission in myasthenia gravis: electrophysiologic study with intracellular microelectrodes. We studied the effects of normal and myasthenic sera on the miniature endplate potential (MEPP) and resting membrane potential (RP) of rat muscle in vitro by conventional intracellular microelectrode techniques. Normal sera had little or no effect on either the amplitude or frequency of MEPP or RP. On the other hand, MEPP amplitude was reduced in each of nine muscles during exposure to myasthenic sera; five of these muscles showed a significant difference, by student's t-test, from the values in a control solution. The half decay time of diminished MEPP remained unchanged. MEPP frequency and RP were not affected by myasthenic sera. The reduced amplitude of the MEPP was almost completely restored when the muscle was washed with a control solution for more than 30 minutes. These observations indicate that myasthenic sera contain factors that bind reversibly with the acetylcholine receptor and reduce postsynaptic responses to acetylcholine."}
{"id": "PMID:210424", "title": "Histochemical labeling of beta-adrenergic receptors in the mouse central nervous system by 9-amino-acridin propranolol.", "content": "A new fluorescent beta-adrenergic antagonist, 9-amino-acridin propranolol (9-AAP), was administered intravenously to living mice. In the cerebral cortex, the highest concentration of 9-AAP was noted in the hippocampal formation, where it distinctly labeled the hippocampal pyramidal cell layer and the granule cell layer of the dentate gryus. High uptake occurred in the pyramidal cell layer of the piriform cortex. In the neocortex, fluorescence was less dense and more diffuse but confined to the basal layers. A similar pattern was observed in the basal layers of the cingulate cortex, but an additional high-density dotted fluorescence labeled its layer II. In the cerebellar cortex, 9-AAP was localized within the Purkinje cell layer. In the spinal cord, the highest density of fluorescence was observed in the nuclear collections of alpha-motoneurons. The findings were similar to those observed in the central nervous system of the rat and support the reproducibility of the method. 9-AAP may be used in vivo as a fluorescent probe to map out the central beta-adrenergic receptor system.", "contents": "Histochemical labeling of beta-adrenergic receptors in the mouse central nervous system by 9-amino-acridin propranolol. A new fluorescent beta-adrenergic antagonist, 9-amino-acridin propranolol (9-AAP), was administered intravenously to living mice. In the cerebral cortex, the highest concentration of 9-AAP was noted in the hippocampal formation, where it distinctly labeled the hippocampal pyramidal cell layer and the granule cell layer of the dentate gryus. High uptake occurred in the pyramidal cell layer of the piriform cortex. In the neocortex, fluorescence was less dense and more diffuse but confined to the basal layers. A similar pattern was observed in the basal layers of the cingulate cortex, but an additional high-density dotted fluorescence labeled its layer II. In the cerebellar cortex, 9-AAP was localized within the Purkinje cell layer. In the spinal cord, the highest density of fluorescence was observed in the nuclear collections of alpha-motoneurons. The findings were similar to those observed in the central nervous system of the rat and support the reproducibility of the method. 9-AAP may be used in vivo as a fluorescent probe to map out the central beta-adrenergic receptor system."}
{"id": "PMID:210428", "title": "[Results and prospects of therapy of type IV dyslipidemia with chenic acid].", "content": "Administration of 500 mg/day chenodeoxycholic acid for 60 days in a series of 44 patients with type IV dyslipidaemia led to gradual normalisation of triglycerides by the end of the treatment. Falls were greater in subjects with initially higher values, but were independent of age, sex, weight and type of diet. Further falls were obtained by repeating the treatment in some cases when prebetalipoproteins rose again. Decreases were already evident by the 5th day (about 24%) and could be obtained with only 4 mg/Kg/day. The rapid effect of the acid and its specific action on prebetalipoproteins were demonstrated by examination of lipid curves after a glyco-lipid load with and without pretreatment with chenic acid. Encouragement of the shunt of triacylglycerols towards the phosphoglycerides during hepatic synthesis of triglycerides is put forward as the most likely mechanism of action in endogenous hyper-triglyceridaemia. The chemical composition of bile is interfered with, which may explain why cholesterol lithiasis is significantly more common in type IV dyslipidaemia than in other forms and in controls, as shown by statistical analysis.", "contents": "[Results and prospects of therapy of type IV dyslipidemia with chenic acid]. Administration of 500 mg/day chenodeoxycholic acid for 60 days in a series of 44 patients with type IV dyslipidaemia led to gradual normalisation of triglycerides by the end of the treatment. Falls were greater in subjects with initially higher values, but were independent of age, sex, weight and type of diet. Further falls were obtained by repeating the treatment in some cases when prebetalipoproteins rose again. Decreases were already evident by the 5th day (about 24%) and could be obtained with only 4 mg/Kg/day. The rapid effect of the acid and its specific action on prebetalipoproteins were demonstrated by examination of lipid curves after a glyco-lipid load with and without pretreatment with chenic acid. Encouragement of the shunt of triacylglycerols towards the phosphoglycerides during hepatic synthesis of triglycerides is put forward as the most likely mechanism of action in endogenous hyper-triglyceridaemia. The chemical composition of bile is interfered with, which may explain why cholesterol lithiasis is significantly more common in type IV dyslipidaemia than in other forms and in controls, as shown by statistical analysis."}
{"id": "PMID:210429", "title": "[Malignant insuloma. Evaluation of the response to treatment with streptozotocin, using selective arteriography of the celiac axis].", "content": "A patients with metastatic insulin-producing islet-cell carcinoma has been treated with Streptozotocin intravenously and studied by selective celiac angiography during treatment. A 50% decrease of the tumor's size has been demonstrated by this technique after a total dose of 19 grams of the drug together with return to normal of the serum-insulin and blood-glucose values. The usefulness of angiography in evaluating the tumor response to Streptozotocin and in managing chemotherapy is discussed.", "contents": "[Malignant insuloma. Evaluation of the response to treatment with streptozotocin, using selective arteriography of the celiac axis]. A patients with metastatic insulin-producing islet-cell carcinoma has been treated with Streptozotocin intravenously and studied by selective celiac angiography during treatment. A 50% decrease of the tumor's size has been demonstrated by this technique after a total dose of 19 grams of the drug together with return to normal of the serum-insulin and blood-glucose values. The usefulness of angiography in evaluating the tumor response to Streptozotocin and in managing chemotherapy is discussed."}
{"id": "PMID:210431", "title": "Cytomegalovirus infections in renal allograft recipients: correlative studies with histocompatibility antigens.", "content": "We studied 32 renal allograft recipients in order to determine whether or not any correlation could be demonstrated between the HLA and development of cytomegalovirus infection. There was a positive stastical correlation (P less than 0.01) of the development of cytomegaloviraemia and the number of HLA antigens mismatched in the recipient. There was no correlation between specific HLA antigens and predisposition to develop cytomegalovirus infection. The implication of our observations with regard to the pathogenesis of cytomegalovirus infection in renal allograft recipients is discussed.", "contents": "Cytomegalovirus infections in renal allograft recipients: correlative studies with histocompatibility antigens. We studied 32 renal allograft recipients in order to determine whether or not any correlation could be demonstrated between the HLA and development of cytomegalovirus infection. There was a positive stastical correlation (P less than 0.01) of the development of cytomegaloviraemia and the number of HLA antigens mismatched in the recipient. There was no correlation between specific HLA antigens and predisposition to develop cytomegalovirus infection. The implication of our observations with regard to the pathogenesis of cytomegalovirus infection in renal allograft recipients is discussed."}
{"id": "PMID:210433", "title": "Uncomplicated pregnancy following oral contraceptive-induced liver hepatoma.", "content": "A patient who used oral contraceptives who had had a partial hepatectomy for benign hepatic cell adenoma became pregnant 3 years after surgery. No diagnosed liver complicaions resulted during the pregnancy or the postpartum period.", "contents": "Uncomplicated pregnancy following oral contraceptive-induced liver hepatoma. A patient who used oral contraceptives who had had a partial hepatectomy for benign hepatic cell adenoma became pregnant 3 years after surgery. No diagnosed liver complicaions resulted during the pregnancy or the postpartum period."}
{"id": "PMID:210434", "title": "Postpartum cytomegalovirus infection. A hazard of multiple transfusions.", "content": "A patient whose postpartum course included the defibrination syndrome and Bacteroides septicemia developed recurrent high fever. Cytomegalovirus infection was suspected on the basis of the clinical features and a history of massive blood transfusion, and was confirmed by subsequent observations. Recognition of this disease and its typically benign course averts the need for extensive diagnostic procedures, exploration, and empiric drug therapy trials.", "contents": "Postpartum cytomegalovirus infection. A hazard of multiple transfusions. A patient whose postpartum course included the defibrination syndrome and Bacteroides septicemia developed recurrent high fever. Cytomegalovirus infection was suspected on the basis of the clinical features and a history of massive blood transfusion, and was confirmed by subsequent observations. Recognition of this disease and its typically benign course averts the need for extensive diagnostic procedures, exploration, and empiric drug therapy trials."}
{"id": "PMID:210435", "title": "Adrenocortical response to ACTH stimulation in postmature newborns.", "content": "Diminished total plasma cortisol levels have been demonstrated in postmature neonates, suggesting that fetal glucocorticoids may be involved in the cause of postmaturity. This hypothesis was tested by adrenocortical stimulation in 32 newborns: 12 were postmature; 12 were postterm, but not postmature; and 8 were normal term neonates. The mean pre- and poststimulation total plasma cortisol levels were 3.9 and 50.9 microgram/100 ml, respectively, for the postmature newborns, 9.7 and 44.0 microgram/100 ml for the postterm, but nonpostmature newborns, and 9.8 and 37.1 microgram/100 ml for the normal term newborns. The differences in the poststimulation rise in plasma cortisol between the postmature and merely postterm infants or between the postterm and normal term infants were not statistically significant. The mean poststimulation cortisol rise in the postmature group exceeded that of the normal term group (P less than 0.05). The adequacy and promptness of response to adrenocortical stimulation eliminate the likelihood of adrenal insufficiency in postmature infants.", "contents": "Adrenocortical response to ACTH stimulation in postmature newborns. Diminished total plasma cortisol levels have been demonstrated in postmature neonates, suggesting that fetal glucocorticoids may be involved in the cause of postmaturity. This hypothesis was tested by adrenocortical stimulation in 32 newborns: 12 were postmature; 12 were postterm, but not postmature; and 8 were normal term neonates. The mean pre- and poststimulation total plasma cortisol levels were 3.9 and 50.9 microgram/100 ml, respectively, for the postmature newborns, 9.7 and 44.0 microgram/100 ml for the postterm, but nonpostmature newborns, and 9.8 and 37.1 microgram/100 ml for the normal term newborns. The differences in the poststimulation rise in plasma cortisol between the postmature and merely postterm infants or between the postterm and normal term infants were not statistically significant. The mean poststimulation cortisol rise in the postmature group exceeded that of the normal term group (P less than 0.05). The adequacy and promptness of response to adrenocortical stimulation eliminate the likelihood of adrenal insufficiency in postmature infants."}
{"id": "PMID:210436", "title": "Lipofuscin in salivary glands in health and disease.", "content": "Lipofuscin granules were observed in normal salivary glands (parotid, submandibular, and minor salivary glands). The pigment was confined mainly to the epithelial cells of the intralobular ducts, but isolated granules were also found in acinar cells and myoepithelial cells. In chronic sialadenitis pigment granules were found in the intralobular epithelial cells and in macrophages in the surrounding ionnective tissue. In benign epithelial tumors pigment granules were observed within neoplastic epithelial cells and in macrophages in the stroma, while malignant tumors displayed pigmented granules only in macrophages in the stroma.", "contents": "Lipofuscin in salivary glands in health and disease. Lipofuscin granules were observed in normal salivary glands (parotid, submandibular, and minor salivary glands). The pigment was confined mainly to the epithelial cells of the intralobular ducts, but isolated granules were also found in acinar cells and myoepithelial cells. In chronic sialadenitis pigment granules were found in the intralobular epithelial cells and in macrophages in the surrounding ionnective tissue. In benign epithelial tumors pigment granules were observed within neoplastic epithelial cells and in macrophages in the stroma, while malignant tumors displayed pigmented granules only in macrophages in the stroma."}
{"id": "PMID:210440", "title": "Serum lipids and lipoproteins at birth in a biracial population: the Bogalusa heart study.", "content": "The lipid profile, total cholesterol, triglycerides, and lipoproteins (beta-, pre-beta-, and alpha-) of cord blood, is presented for 419 black and white infants (94% of the eligible population) born during an 18-month period in Bogalusa, Louisiana. At birth, white neonates of both sexes had higher average levels than black neonates of total cholesterol and beta-lipoproteins. White girls among the four race-sex groups had the highest cord blood levels of total cholesterol, beta-lipoproteins, and alpha-lipoproteins. Neither stress at delivery, birthweight, socioeconomic status, nor season of the year had an observable effect on any of the lipid or lipoprotein levels. The magnitude and direction of the relationships between the respective lipids and lipoproteins in cord blood were similar to those we have observed in preschool and school-aged children in the same community. Total cholesterol was highly correlated with both beta- and alpha-lipoproteins; triglycerides were correlated with pre-beta-lipoproteins but inversely with alpha-lipoproteins. These observations suggest that basic biochemical relationships are already established at birth.", "contents": "Serum lipids and lipoproteins at birth in a biracial population: the Bogalusa heart study. The lipid profile, total cholesterol, triglycerides, and lipoproteins (beta-, pre-beta-, and alpha-) of cord blood, is presented for 419 black and white infants (94% of the eligible population) born during an 18-month period in Bogalusa, Louisiana. At birth, white neonates of both sexes had higher average levels than black neonates of total cholesterol and beta-lipoproteins. White girls among the four race-sex groups had the highest cord blood levels of total cholesterol, beta-lipoproteins, and alpha-lipoproteins. Neither stress at delivery, birthweight, socioeconomic status, nor season of the year had an observable effect on any of the lipid or lipoprotein levels. The magnitude and direction of the relationships between the respective lipids and lipoproteins in cord blood were similar to those we have observed in preschool and school-aged children in the same community. Total cholesterol was highly correlated with both beta- and alpha-lipoproteins; triglycerides were correlated with pre-beta-lipoproteins but inversely with alpha-lipoproteins. These observations suggest that basic biochemical relationships are already established at birth."}
{"id": "PMID:210437", "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:210444", "title": "Agarose linked adenosine and guanosine-5'-monophosphate; a new general method for the coupling of ribonucleotides to polymers through their cis-diols.", "content": "Condensation of the cis-diol of adenosine (1a) or guanosine (1b) with ethyl levulinate led to the acetal-esters 2a or 2b. Phosphorylation with phosphorous oxide trichloride converted them into their 5'-monophosphates. On alkaline hydrolysis the acetal-esters 2a,b as well as their 5'-monophosphates gave the carboxylic acid derivatives 3a,b and 4a,b, respectively. Condensation of these acid derivatives with aminohexyl-agarose (5) using water soluble N-ethyl-N'-(3'-dimethyl-aminopropyl)-carbodiimide hydrochloride as coupling reagent led to the new polymers 6a/6b and 7a/7b. This method of preparing resin linked adenosine and guanosine derivatives should be generally applicable to any ribonucleoside or ribonucleotide with a cis-diol. Because of the widespread occurence of these molecules, particularly as cofactors of enzymes, the new polymers might be useful tools for the purification of certain classes of enzymes by affinity chromatography.", "contents": "Agarose linked adenosine and guanosine-5'-monophosphate; a new general method for the coupling of ribonucleotides to polymers through their cis-diols. Condensation of the cis-diol of adenosine (1a) or guanosine (1b) with ethyl levulinate led to the acetal-esters 2a or 2b. Phosphorylation with phosphorous oxide trichloride converted them into their 5'-monophosphates. On alkaline hydrolysis the acetal-esters 2a,b as well as their 5'-monophosphates gave the carboxylic acid derivatives 3a,b and 4a,b, respectively. Condensation of these acid derivatives with aminohexyl-agarose (5) using water soluble N-ethyl-N'-(3'-dimethyl-aminopropyl)-carbodiimide hydrochloride as coupling reagent led to the new polymers 6a/6b and 7a/7b. This method of preparing resin linked adenosine and guanosine derivatives should be generally applicable to any ribonucleoside or ribonucleotide with a cis-diol. Because of the widespread occurence of these molecules, particularly as cofactors of enzymes, the new polymers might be useful tools for the purification of certain classes of enzymes by affinity chromatography."}
{"id": "PMID:210445", "title": "Fetal limb deformities due to amniotic constrictions (a possible consequence of preceding amniocentesis).", "content": "The nature and origin of circular constrictions and intrauterine amputations can be studied more effectively in the fetus than in the newborn. Two cases of fetal micro- and syndactyly secondary to ring constrictions are discussed with respect to morphological processes. The amniotic membranes display active chorionic proliferation in addition to amniotic rupture and passive string formation. Moreover, association between the origin of amniotic bands and preceding amniocentesis seems to be possible in one case though it is difficult to ascertain.", "contents": "Fetal limb deformities due to amniotic constrictions (a possible consequence of preceding amniocentesis). The nature and origin of circular constrictions and intrauterine amputations can be studied more effectively in the fetus than in the newborn. Two cases of fetal micro- and syndactyly secondary to ring constrictions are discussed with respect to morphological processes. The amniotic membranes display active chorionic proliferation in addition to amniotic rupture and passive string formation. Moreover, association between the origin of amniotic bands and preceding amniocentesis seems to be possible in one case though it is difficult to ascertain."}
{"id": "PMID:210447", "title": "Uremic hyperlipidemia: the nature of the problem.", "content": "Increased triglyceride and reduced HDL cholesterol levels are 2 risk factors for atherosclerosis with a high prevalence in chronic hemodialysis patients. Whether they have the same significance in these patients as in the general population is not known. Nonethless, therapy may be indicated because of the severity of the atherosclerotic disorder. The most appropriate drug, clofibrate, is renally excreted and can be used safely if the dosage is markedly reduced. No data exists in any population that such therapy is beneficial.", "contents": "Uremic hyperlipidemia: the nature of the problem. Increased triglyceride and reduced HDL cholesterol levels are 2 risk factors for atherosclerosis with a high prevalence in chronic hemodialysis patients. Whether they have the same significance in these patients as in the general population is not known. Nonethless, therapy may be indicated because of the severity of the atherosclerotic disorder. The most appropriate drug, clofibrate, is renally excreted and can be used safely if the dosage is markedly reduced. No data exists in any population that such therapy is beneficial."}
{"id": "PMID:210448", "title": "Adenosine kinase initiates the major route of ribavirin activation in a cultured human cell line.", "content": "Inhibition of IMP dehydrogenase (EC 1.2.1.14) by ribavirin causes the normal human lymphoblast to excrete increased amounts of newly formed purine into the culture medium. In order for ribavirin to be active as an inhibitor of the dehydrogenase, this synthetic nucleoside must be phosphorylated. The effect of ribavirin on purine excretion has been determined with a normal lymphoblast line, and with lymphoblast lines deficient in hypoxanthine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyl-transferase, EC 2.4.2.8), in adenosine kinase (ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20), and in both hypoxanthine phosphoribosyltransferase and adenosine kinase. Resistance to the effect of ribavirin on purine excretion was associated only with those cell lines deficient in adenosine kinase activity. These cell lines have normal deoxyadenosine kinase (ATP:deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76) activity. Therefore, the nucleoside kinase activity responsible for ribavirin phosphorylation is adenosine kinase.", "contents": "Adenosine kinase initiates the major route of ribavirin activation in a cultured human cell line. Inhibition of IMP dehydrogenase (EC 1.2.1.14) by ribavirin causes the normal human lymphoblast to excrete increased amounts of newly formed purine into the culture medium. In order for ribavirin to be active as an inhibitor of the dehydrogenase, this synthetic nucleoside must be phosphorylated. The effect of ribavirin on purine excretion has been determined with a normal lymphoblast line, and with lymphoblast lines deficient in hypoxanthine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyl-transferase, EC 2.4.2.8), in adenosine kinase (ATP:adenosine 5'-phosphotransferase, EC 2.7.1.20), and in both hypoxanthine phosphoribosyltransferase and adenosine kinase. Resistance to the effect of ribavirin on purine excretion was associated only with those cell lines deficient in adenosine kinase activity. These cell lines have normal deoxyadenosine kinase (ATP:deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76) activity. Therefore, the nucleoside kinase activity responsible for ribavirin phosphorylation is adenosine kinase."}
{"id": "PMID:210449", "title": "ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase.", "content": "In the presence of ATP and a cytosolic factor, cholera toxin fragment A1 catalyzes the transfer of ADP-ribose from NAD to a number of soluble and membrane-bound proteins of the pigeon erythrocyte. Evidence is presented that suggests that the most readily modified membrane protein (Mr 42,000) is the adenylate cyclase-associated GTP-binding protein. Its modification by toxin is stimulated by guanine nucleotides. Adenylate cyclase activity increases in parallel with the addition of ADP-ribose to this protein and decreases in parallel with the subsequent reversal of ADP-ribosylation by toxin and nicotinamide. The protein is only accessible to toxin A subunits if the erythrocytes are lysed. When adenylate cyclase activity reaches a maximum, the number of ADP-ribose residues bound to this protein (about 1500 per cell) is similar to the reported number of beta-adrenergic receptors.", "contents": "ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. In the presence of ATP and a cytosolic factor, cholera toxin fragment A1 catalyzes the transfer of ADP-ribose from NAD to a number of soluble and membrane-bound proteins of the pigeon erythrocyte. Evidence is presented that suggests that the most readily modified membrane protein (Mr 42,000) is the adenylate cyclase-associated GTP-binding protein. Its modification by toxin is stimulated by guanine nucleotides. Adenylate cyclase activity increases in parallel with the addition of ADP-ribose to this protein and decreases in parallel with the subsequent reversal of ADP-ribosylation by toxin and nicotinamide. The protein is only accessible to toxin A subunits if the erythrocytes are lysed. When adenylate cyclase activity reaches a maximum, the number of ADP-ribose residues bound to this protein (about 1500 per cell) is similar to the reported number of beta-adrenergic receptors."}
{"id": "PMID:210450", "title": "Oxygen-mediated heterogeneity of apo-low-density lipoprotein.", "content": "Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower molecular weight polypeptide components, as characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. This protein alteration, which correlates temporally with increases in the formation of lipid oxidation products and in the fluorescence of the apoprotein, is markedly reduced when oxygen is excluded or when EDTA or the free-radical-scavenging antioxidants, butylated hydroxytoluene or propyl gallate, are added. The conversion thus appears to be due to a reaction between the protein moiety and auto-oxidizing lipid. The presence of the antibacterial agent sodium azide markedly accelerates the oxidation, suggesting that it should only be used with caution in lipid-containing solutions.", "contents": "Oxygen-mediated heterogeneity of apo-low-density lipoprotein. Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower molecular weight polypeptide components, as characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. This protein alteration, which correlates temporally with increases in the formation of lipid oxidation products and in the fluorescence of the apoprotein, is markedly reduced when oxygen is excluded or when EDTA or the free-radical-scavenging antioxidants, butylated hydroxytoluene or propyl gallate, are added. The conversion thus appears to be due to a reaction between the protein moiety and auto-oxidizing lipid. The presence of the antibacterial agent sodium azide markedly accelerates the oxidation, suggesting that it should only be used with caution in lipid-containing solutions."}
{"id": "PMID:210451", "title": "Heat-stable low molecular weight form of phosphodiesterases from bovine pineal gland.", "content": "The 105,000 X g supernatant fraction of bovine pineal gland contains a phosphodiesterase activity that hydrolyzes both cyclic AMP and cyclic GMP. The rate of hydrolysis is 4-5 times greater with cyclic GMP as substrate than with cyclic AMP. Chromatography of supernatant fraction on Sephadex G-150 resolves phosphodiesterase activity into two fractions designated PDE I and PDE II. These are distinguishable on the basis of their molecular size, substrate specificity, and kinetic parameters. PDE I hydrolyzes cyclic GMP at a faster rate than cyclic AMP and has a molecular weight of 163,000. PDE II appears to be a smaller protein with a molecular weight of 24,400 and is specific for cyclic AMP. PDE I has apparent Km values of 83 and 53 micron for cyclic AMP and cyclic GMP, respectively, whereas PDE II exhibits an apparent Km value of 330 micron for cyclic AMP. With subsaturating concentrations of cyclic AMP as substrate, the phosphodiesterase activity of PDE I is inhibited by the addition of cyclic GMP. However, PDE II activity remains unaffected by cyclic GMP even at concentrations up to 125 micron. PDE II appears to be thermostable, losing only 20% of its activity on heating at 80 degrees for 2 min. Similar treatment completely abolishes the enzyme activity of PDE I.", "contents": "Heat-stable low molecular weight form of phosphodiesterases from bovine pineal gland. The 105,000 X g supernatant fraction of bovine pineal gland contains a phosphodiesterase activity that hydrolyzes both cyclic AMP and cyclic GMP. The rate of hydrolysis is 4-5 times greater with cyclic GMP as substrate than with cyclic AMP. Chromatography of supernatant fraction on Sephadex G-150 resolves phosphodiesterase activity into two fractions designated PDE I and PDE II. These are distinguishable on the basis of their molecular size, substrate specificity, and kinetic parameters. PDE I hydrolyzes cyclic GMP at a faster rate than cyclic AMP and has a molecular weight of 163,000. PDE II appears to be a smaller protein with a molecular weight of 24,400 and is specific for cyclic AMP. PDE I has apparent Km values of 83 and 53 micron for cyclic AMP and cyclic GMP, respectively, whereas PDE II exhibits an apparent Km value of 330 micron for cyclic AMP. With subsaturating concentrations of cyclic AMP as substrate, the phosphodiesterase activity of PDE I is inhibited by the addition of cyclic GMP. However, PDE II activity remains unaffected by cyclic GMP even at concentrations up to 125 micron. PDE II appears to be thermostable, losing only 20% of its activity on heating at 80 degrees for 2 min. Similar treatment completely abolishes the enzyme activity of PDE I."}
{"id": "PMID:210452", "title": "Guanosinetriphosphatase activity dependent on elongation factor Tu and ribosomal protein L7/L12.", "content": "Incubation of electrophoretically pure samples of the Escherichia coli 50S ribosomal protein L7/L12 together with elongation factor Tu leads to the hydrolysis of GTP. Addition of elongation factor Ts stimulates this reaction. Elongation factor G cannot replace elongation factor Tu for the ribosome-free GTPase reaction dependent on L7/L12. The data suggest that elongation factor Tu and the protein L7/L12 interact directly at the ribosomal A site.", "contents": "Guanosinetriphosphatase activity dependent on elongation factor Tu and ribosomal protein L7/L12. Incubation of electrophoretically pure samples of the Escherichia coli 50S ribosomal protein L7/L12 together with elongation factor Tu leads to the hydrolysis of GTP. Addition of elongation factor Ts stimulates this reaction. Elongation factor G cannot replace elongation factor Tu for the ribosome-free GTPase reaction dependent on L7/L12. The data suggest that elongation factor Tu and the protein L7/L12 interact directly at the ribosomal A site."}
{"id": "PMID:210453", "title": "Pseudomonas aeruginosa exoenzyme S: an adenosine diphosphate ribosyltransferase distinct from toxin A.", "content": "Pseudomonas aeruginosa exoenzyme S is an adenosine diphosphate ribosyltransferase distinct from Pseudomonas toxin A. Exoenzyme S catalyzes the transfer of radioactivity from all portions of radiolabeled NAD+ except nicotinamide. Digestion of the radiolabeled product(s) formed in the presence of [adenine-14C]NAD+ and exoenzyme S with snake venom phosphodiesterase yields only AMP, suggesting that ADP-ribose is present as monomers and not as poly(ADP-ribose). Exoenzyme S does not catalyze the transfer of ADP-ribose from NAD+ to elongation factor 2, as do toxin A and diphtheria toxin, but to one or more other proteins present in crude extracts of wheat germ or rabbit reticulocytes and in partially purified preparations of elongation factor I. The ADP-ribosyltransferase activity of exoenzyme S is distinct from toxin A by several tests: it is not neutralized by toxin A antibody, it is destroyed rather than potentiated by pretreatment with urea, and it is more heat stable. These latter observations and the substrate specificity suggest that exoenzyme S is different from any previously described prokaryotic ADP-ribosyltransferase.", "contents": "Pseudomonas aeruginosa exoenzyme S: an adenosine diphosphate ribosyltransferase distinct from toxin A. Pseudomonas aeruginosa exoenzyme S is an adenosine diphosphate ribosyltransferase distinct from Pseudomonas toxin A. Exoenzyme S catalyzes the transfer of radioactivity from all portions of radiolabeled NAD+ except nicotinamide. Digestion of the radiolabeled product(s) formed in the presence of [adenine-14C]NAD+ and exoenzyme S with snake venom phosphodiesterase yields only AMP, suggesting that ADP-ribose is present as monomers and not as poly(ADP-ribose). Exoenzyme S does not catalyze the transfer of ADP-ribose from NAD+ to elongation factor 2, as do toxin A and diphtheria toxin, but to one or more other proteins present in crude extracts of wheat germ or rabbit reticulocytes and in partially purified preparations of elongation factor I. The ADP-ribosyltransferase activity of exoenzyme S is distinct from toxin A by several tests: it is not neutralized by toxin A antibody, it is destroyed rather than potentiated by pretreatment with urea, and it is more heat stable. These latter observations and the substrate specificity suggest that exoenzyme S is different from any previously described prokaryotic ADP-ribosyltransferase."}
{"id": "PMID:210454", "title": "Nucleotide sequence homology at the 3' termini of RNA from vesicular stomatitis virus and its defective interfering particles.", "content": "Vesicular stomatitis virus (VSV) and defective interfering (DI) particle RNAs were labeled at their 3' ends by using RNA ligase and cytidine 3',5'-bis[32P]phosphate. The RNAs were subjected to partial digestion with alkali and analyzed by oligonucleotide fingerprinting in two dimensions. VSV and DI particle RNAs have complete sequence homology for the first eight bases from the 3' end. The following four positions contain three mismatched nucleotides in which guanosine residues in one strand are replaced by uridine residues in the other. There is again complete homology for the next five bases (positions 13-17). The locations of purine residues within the sequence were confirmed by partial digestion with RNase T1 and RNase U2 and separation by size on 20% acrylamide gels. The latter method also indicated that sequences of VSV and DI particle RNAs diverge beyond the 18th nucleotide from the 3' termini.", "contents": "Nucleotide sequence homology at the 3' termini of RNA from vesicular stomatitis virus and its defective interfering particles. Vesicular stomatitis virus (VSV) and defective interfering (DI) particle RNAs were labeled at their 3' ends by using RNA ligase and cytidine 3',5'-bis[32P]phosphate. The RNAs were subjected to partial digestion with alkali and analyzed by oligonucleotide fingerprinting in two dimensions. VSV and DI particle RNAs have complete sequence homology for the first eight bases from the 3' end. The following four positions contain three mismatched nucleotides in which guanosine residues in one strand are replaced by uridine residues in the other. There is again complete homology for the next five bases (positions 13-17). The locations of purine residues within the sequence were confirmed by partial digestion with RNase T1 and RNase U2 and separation by size on 20% acrylamide gels. The latter method also indicated that sequences of VSV and DI particle RNAs diverge beyond the 18th nucleotide from the 3' termini."}
{"id": "PMID:210455", "title": "Identification of epoxide hydrase as the preneoplastic antigen in rat liver hyperplastic nodules.", "content": "A liver microsomal protein, previously referred to as preneoplastic antigen, from hyperplastic nodules of rats fed a diet containing 2-acetylaminofluorene has been identified as the enzyme epoxide hydrase [glycol hydro-lyase (epoxideforming), EC 4.2.1.63]. Purified preneoplastic antigen from hyperplastic nodules and purified rat liver microsomal epoxide hydrase are immunochemically identical on the basis of Ouchterlony double-diffusion analysis. In addition, the purified proteins have identical minimum molecular weights in sodium dodecyl sulfate/polyacrylamide gels, and both proteins catalyze the hydration of arene oxides to dihydrodiols. Chronic feeding of 2-acetylaminofluorene to rats results in a 5- to 7-fold increase in epoxide hydrase activity in rat liver. The induced level of the enzyme is maintained in developing hyperplastic nodules and hepatomas but not in the nontumor tissue after removal of the carcinogen from the diet.", "contents": "Identification of epoxide hydrase as the preneoplastic antigen in rat liver hyperplastic nodules. A liver microsomal protein, previously referred to as preneoplastic antigen, from hyperplastic nodules of rats fed a diet containing 2-acetylaminofluorene has been identified as the enzyme epoxide hydrase [glycol hydro-lyase (epoxideforming), EC 4.2.1.63]. Purified preneoplastic antigen from hyperplastic nodules and purified rat liver microsomal epoxide hydrase are immunochemically identical on the basis of Ouchterlony double-diffusion analysis. In addition, the purified proteins have identical minimum molecular weights in sodium dodecyl sulfate/polyacrylamide gels, and both proteins catalyze the hydration of arene oxides to dihydrodiols. Chronic feeding of 2-acetylaminofluorene to rats results in a 5- to 7-fold increase in epoxide hydrase activity in rat liver. The induced level of the enzyme is maintained in developing hyperplastic nodules and hepatomas but not in the nontumor tissue after removal of the carcinogen from the diet."}
{"id": "PMID:210456", "title": "Identification of the major polyadenylylated transcription products and the genes active in their synthesis in a rat insulinoma.", "content": "Three RNA fractions with molecular weights of 200,000, 280,000, and 360,000, have been identified as the major polyadenylylated transcription products in a transplantable rat pancreatic islet cell tumor that synthesizes insulin. These three RNAs share sequence homology as demonstrated by comparisons of both partial and complete RNase T1 digestion products. The 200,000 and 280,000 molecular weight species hybridize primarily with three EcoRI restriction fragments of the rat genome having molecular weights of 1.4 X 10(6), 1.6 X 10(6), and 6.0 X 10(6). The 360,000 molecular weight species hybridizes preferentially with the 6.0 X 10(6) molecular weight DNA fragment.", "contents": "Identification of the major polyadenylylated transcription products and the genes active in their synthesis in a rat insulinoma. Three RNA fractions with molecular weights of 200,000, 280,000, and 360,000, have been identified as the major polyadenylylated transcription products in a transplantable rat pancreatic islet cell tumor that synthesizes insulin. These three RNAs share sequence homology as demonstrated by comparisons of both partial and complete RNase T1 digestion products. The 200,000 and 280,000 molecular weight species hybridize primarily with three EcoRI restriction fragments of the rat genome having molecular weights of 1.4 X 10(6), 1.6 X 10(6), and 6.0 X 10(6). The 360,000 molecular weight species hybridizes preferentially with the 6.0 X 10(6) molecular weight DNA fragment."}
{"id": "PMID:210457", "title": "Binding to chromosomes of herpes simplex-related antigens in biochemically transformed cells.", "content": "Association of herpes simplex virus (HSV)-related antigens with chromosomes was demonstrated in human and mouse cells biochemically transformed by HSV that had been irradiated with ultraviolet light. This was accomplished by using peroxidase-anti-peroxidase immunological staining with rabbit antisera that had high neutralizing titers against both HSV-specific thymidine kinase activity and virus infectivity. Antisera-against HSV did not react with chromosomes of uninfected cells nor did normal sera react with any of the constitutents of biochemically transformed cells. Methanol/acetic acid treatment of biochemically transformed cells eliminated their nuclear staining for HSV-related antigens. In vitro binding of HSV-related antigens to chromosomes was demonstrated by incubating soluble antigens from high salt extracts of HSV-infected cells with methanol/acetic acid-fixed chromosomes of biochemically transformed or uninfected cells, followed by exposure to antiserum against HSV and peroxidase-anti-peroxidase staining. There was no staining when soluble extracts from uninfected cells were substituted for those from HSV-infected cells. The results show that cells biochemically transformed and lytically infected by HSV, respectively, contain antigens, which like the Epstein-Barr virus-associated nuclear antigen (EBNA), bind to chromosomes in vivo and in vitro.", "contents": "Binding to chromosomes of herpes simplex-related antigens in biochemically transformed cells. Association of herpes simplex virus (HSV)-related antigens with chromosomes was demonstrated in human and mouse cells biochemically transformed by HSV that had been irradiated with ultraviolet light. This was accomplished by using peroxidase-anti-peroxidase immunological staining with rabbit antisera that had high neutralizing titers against both HSV-specific thymidine kinase activity and virus infectivity. Antisera-against HSV did not react with chromosomes of uninfected cells nor did normal sera react with any of the constitutents of biochemically transformed cells. Methanol/acetic acid treatment of biochemically transformed cells eliminated their nuclear staining for HSV-related antigens. In vitro binding of HSV-related antigens to chromosomes was demonstrated by incubating soluble antigens from high salt extracts of HSV-infected cells with methanol/acetic acid-fixed chromosomes of biochemically transformed or uninfected cells, followed by exposure to antiserum against HSV and peroxidase-anti-peroxidase staining. There was no staining when soluble extracts from uninfected cells were substituted for those from HSV-infected cells. The results show that cells biochemically transformed and lytically infected by HSV, respectively, contain antigens, which like the Epstein-Barr virus-associated nuclear antigen (EBNA), bind to chromosomes in vivo and in vitro."}
{"id": "PMID:210458", "title": "Different regulation of insulin receptors in intracellular (Golgi) and plasma membranes from livers of obese and lean mice.", "content": "Insulin binding to Golgi and plasmalemma fractions from the liver of obese (ob/bo and db/db) and lean control mice was studied. The specficiity of binding in Golgi fractions (Golgi vesicles and Golgi cisternae) was identical to that observed previously in rat liver Golgi fractions and plasmalemma. Binding to plasmalemma was much lower in obese compared to lean mice, but binding to Golgi cisternae was either not changed (ob/ob) or slightly increased (db/db) in obese compared to lean littermates. These observations suggest that intracellular (Golgi cisternae) insulin receptors are regulated differently from those of the plasmalemma. We propose that insulin affects hepatic receptor content in two different ways. On the one hand plasmalemma receptor loss is accelerated, and on the other hand intracellular receptor production is increased. This model can explain in one framework the effect on insulin in reducing and prolactin in augmenting the level of their respective hepatic receptors.", "contents": "Different regulation of insulin receptors in intracellular (Golgi) and plasma membranes from livers of obese and lean mice. Insulin binding to Golgi and plasmalemma fractions from the liver of obese (ob/bo and db/db) and lean control mice was studied. The specficiity of binding in Golgi fractions (Golgi vesicles and Golgi cisternae) was identical to that observed previously in rat liver Golgi fractions and plasmalemma. Binding to plasmalemma was much lower in obese compared to lean mice, but binding to Golgi cisternae was either not changed (ob/ob) or slightly increased (db/db) in obese compared to lean littermates. These observations suggest that intracellular (Golgi cisternae) insulin receptors are regulated differently from those of the plasmalemma. We propose that insulin affects hepatic receptor content in two different ways. On the one hand plasmalemma receptor loss is accelerated, and on the other hand intracellular receptor production is increased. This model can explain in one framework the effect on insulin in reducing and prolactin in augmenting the level of their respective hepatic receptors."}
{"id": "PMID:210459", "title": "Sites of integration of reticuloendotheliosis virus DNA in chicken DNA.", "content": "The pattern of integration of spleen necrosis virus (SNV) DNA in DNA from a large population of SNV-infected chicken cells was studied by nucleic acid hybridization with iodinated viral RNA by the blotting technique of Southern. SNV DNA was found to be integrated at multiple sites in acutely infected chicken cells. Concomitant with the transition from acute to chronic infection, a shift in the pattern of integration was observed. The majority of integrated SNV DNA found in acutely infected cells was absent from chronically infected cells. This result is consistent with the hypothesis that the cell death that occurs after infection of avian cells with reticuloendotheliosis viruses is a consequence of the multiple integrations of the provirus. Viral DNA was also integrated at multiple sites in chronically infected cells. However, infectious viral DNA molecules in chronically infected cells migrated in a uniform manner in agarose gel electrophoresis after EcoRI digestion (which does not cut viral DNA), indicating that not all integrated SNV copies are equally infectious.", "contents": "Sites of integration of reticuloendotheliosis virus DNA in chicken DNA. The pattern of integration of spleen necrosis virus (SNV) DNA in DNA from a large population of SNV-infected chicken cells was studied by nucleic acid hybridization with iodinated viral RNA by the blotting technique of Southern. SNV DNA was found to be integrated at multiple sites in acutely infected chicken cells. Concomitant with the transition from acute to chronic infection, a shift in the pattern of integration was observed. The majority of integrated SNV DNA found in acutely infected cells was absent from chronically infected cells. This result is consistent with the hypothesis that the cell death that occurs after infection of avian cells with reticuloendotheliosis viruses is a consequence of the multiple integrations of the provirus. Viral DNA was also integrated at multiple sites in chronically infected cells. However, infectious viral DNA molecules in chronically infected cells migrated in a uniform manner in agarose gel electrophoresis after EcoRI digestion (which does not cut viral DNA), indicating that not all integrated SNV copies are equally infectious."}
{"id": "PMID:210460", "title": "Isolation and characterization of a human serum cholesteryl ester transfer protein.", "content": "Human plasma has been shown to contain an apolipoprotein that mediates the transport of cholesteryl ester from high density lipoprotein (HDL) to very low density lipoprotein (VLDL) or low density lipoprotein (LDL). This activity, confined to the density greater than 1.063 g/ml interval, has been isolated from HDL and appears as a single migrating species by anionic or sodium dodecyl sulfate/polyacrylamide gel electrophoresis. It is unreactive to antibodies to the major HDL apolipoproteins. Antibodies prepared against this factor and immobilized on Sepharose remove the capacity of HDL and density greater than 1.21 g/ml fractions as well as whole plasma to transport cholesteryl ester from HDL. The system shows saturation kinetics with respect to plasma LDL and VLDL concentrations, and transport of cholesteryl ester was associated with reciprocal and equimolar back-transport of triglyceride from VLDL and LDL to the HDL fraction. The possible relationship of this apoprotein to apoprotein D is discussed.", "contents": "Isolation and characterization of a human serum cholesteryl ester transfer protein. Human plasma has been shown to contain an apolipoprotein that mediates the transport of cholesteryl ester from high density lipoprotein (HDL) to very low density lipoprotein (VLDL) or low density lipoprotein (LDL). This activity, confined to the density greater than 1.063 g/ml interval, has been isolated from HDL and appears as a single migrating species by anionic or sodium dodecyl sulfate/polyacrylamide gel electrophoresis. It is unreactive to antibodies to the major HDL apolipoproteins. Antibodies prepared against this factor and immobilized on Sepharose remove the capacity of HDL and density greater than 1.21 g/ml fractions as well as whole plasma to transport cholesteryl ester from HDL. The system shows saturation kinetics with respect to plasma LDL and VLDL concentrations, and transport of cholesteryl ester was associated with reciprocal and equimolar back-transport of triglyceride from VLDL and LDL to the HDL fraction. The possible relationship of this apoprotein to apoprotein D is discussed."}
{"id": "PMID:210461", "title": "Identification of the trypanocidal factor in normal human serum: high density lipoprotein.", "content": "The differentiation of Trypanosoma brucei from T. rhodesiense, the causative agent of human sleeping sickness, depends on their relative sensitivities to the cytotoxic effects of normal human serum. The molecule responsible for the specific lysis of T. brucei has now been isolated. Serum lipoproteins were fractionated and purified by ultracentrifugal flotation and chromatography on Bio-Gel A-5m. Trypanocidal activity was recovered in the high density lipoprotein fraction (density, 1.063-1.216 g/ml). Contamination by other serum proteins was checked by crossed immunoelectrophoresis and sodium dodecyl sulfate/acrylamide gel electrophoresis. Only a trace of beta-lipoprotein was found. The trypanocidal activity of pure human high density lipoprotein was identical to that of unfractionated serum when the following were tested: (i) time course of in vitro lysis of T. bruceli; (ii) in vivo destruction of T. brucei; (iii) relative resistance of T. rhodesiense to lysis. Rat or rabbit high density lipoprotein had no trypanocidal activity. Identification of the trypanocidal factor as high density lipoprotein was confirmed by the finding that serum from patients with Tangier disease, an autosomal recessive disorder characterized by a severe deficiency of high density lipoprotein, had no trypanocidal activity.", "contents": "Identification of the trypanocidal factor in normal human serum: high density lipoprotein. The differentiation of Trypanosoma brucei from T. rhodesiense, the causative agent of human sleeping sickness, depends on their relative sensitivities to the cytotoxic effects of normal human serum. The molecule responsible for the specific lysis of T. brucei has now been isolated. Serum lipoproteins were fractionated and purified by ultracentrifugal flotation and chromatography on Bio-Gel A-5m. Trypanocidal activity was recovered in the high density lipoprotein fraction (density, 1.063-1.216 g/ml). Contamination by other serum proteins was checked by crossed immunoelectrophoresis and sodium dodecyl sulfate/acrylamide gel electrophoresis. Only a trace of beta-lipoprotein was found. The trypanocidal activity of pure human high density lipoprotein was identical to that of unfractionated serum when the following were tested: (i) time course of in vitro lysis of T. bruceli; (ii) in vivo destruction of T. brucei; (iii) relative resistance of T. rhodesiense to lysis. Rat or rabbit high density lipoprotein had no trypanocidal activity. Identification of the trypanocidal factor as high density lipoprotein was confirmed by the finding that serum from patients with Tangier disease, an autosomal recessive disorder characterized by a severe deficiency of high density lipoprotein, had no trypanocidal activity."}
{"id": "PMID:210474", "title": "Influence of cyclic AMP on DNA synthesis in slices of regenerating rat liver.", "content": "DNA synthesis in slices of regenerating rat liver is inhibited by adenosine cyclic 3',5'-monophosphate [cAMP]. The number of cells synthesizing DNA as assayed by 2-14C-thymidine incorporation is reduced by 65% in the presence of 10(-3) M cAMP. The inhibition of cAMP is not specific; other adenosine compounds, N6,O2,-dibutyryl adenosine 3',5'-monophosphate, 5'AMP and adenosine have the same effect. Moreover, the concentration of cAMP in the cell required for this inhibition is much higher than the normal levels of cAMP in liver cells.", "contents": "Influence of cyclic AMP on DNA synthesis in slices of regenerating rat liver. DNA synthesis in slices of regenerating rat liver is inhibited by adenosine cyclic 3',5'-monophosphate [cAMP]. The number of cells synthesizing DNA as assayed by 2-14C-thymidine incorporation is reduced by 65% in the presence of 10(-3) M cAMP. The inhibition of cAMP is not specific; other adenosine compounds, N6,O2,-dibutyryl adenosine 3',5'-monophosphate, 5'AMP and adenosine have the same effect. Moreover, the concentration of cAMP in the cell required for this inhibition is much higher than the normal levels of cAMP in liver cells."}
{"id": "PMID:210475", "title": "Cutaneous signs of internal malignant disease.", "content": "An awareness of various dermatoses which reflect internal malignancy will facilitate the physician's ability to recognize or even anticipate malignant disease. There have been several previous reports on this subject. This review emphasizes the nonspecific cutaneous changes associated with malignancy. New skin markers of cancer are also discussed.", "contents": "Cutaneous signs of internal malignant disease. An awareness of various dermatoses which reflect internal malignancy will facilitate the physician's ability to recognize or even anticipate malignant disease. There have been several previous reports on this subject. This review emphasizes the nonspecific cutaneous changes associated with malignancy. New skin markers of cancer are also discussed."}
{"id": "PMID:210476", "title": "Paradoxical effects in sleep and performance of two doses of chlorpromazine.", "content": "Twenty-four subjects were given placebo, 25 mg, and 75 mg of chlorpromazine on three separate occasions. Twelve subjects were treated in the morning and tested for performance during the day. Twelve other subjects received the drug treatments in the evening. Both groups had their EEG stages of sleep recorded during the subsequent night. The low dose of drug shortened the REM/non-REM cycle length in comparison to the high dose, and placebo values were intermediate. In performance tests, visual integration time was impaired by the high dose of the drug. Logical reasoning was slowed by the high dose of the drug in comparison to the low dose, with placebo values intermediate between the two.", "contents": "Paradoxical effects in sleep and performance of two doses of chlorpromazine. Twenty-four subjects were given placebo, 25 mg, and 75 mg of chlorpromazine on three separate occasions. Twelve subjects were treated in the morning and tested for performance during the day. Twelve other subjects received the drug treatments in the evening. Both groups had their EEG stages of sleep recorded during the subsequent night. The low dose of drug shortened the REM/non-REM cycle length in comparison to the high dose, and placebo values were intermediate. In performance tests, visual integration time was impaired by the high dose of the drug. Logical reasoning was slowed by the high dose of the drug in comparison to the low dose, with placebo values intermediate between the two."}
{"id": "PMID:210477", "title": "The differential effect of lithium on noradrenaline- and dopamine-sensitive accumulation of cyclic AMP in guinea pig brain.", "content": "Lithium (Li) in its narrow therapeutic concentration range was found to inhibit only the noradrenaline- and not the dopamine-sensitive accumulation of cyclic AMP in guinea pig brain. The results suggest a pharmacological distinction between the anti-schizophrenic drugs that inhibit dopamine-sensitive cyclic AMP accumulation and Li, an antimanic agent that inhibits specifically only the noradrenaline-sensitive cyclic AMP accumulation.", "contents": "The differential effect of lithium on noradrenaline- and dopamine-sensitive accumulation of cyclic AMP in guinea pig brain. Lithium (Li) in its narrow therapeutic concentration range was found to inhibit only the noradrenaline- and not the dopamine-sensitive accumulation of cyclic AMP in guinea pig brain. The results suggest a pharmacological distinction between the anti-schizophrenic drugs that inhibit dopamine-sensitive cyclic AMP accumulation and Li, an antimanic agent that inhibits specifically only the noradrenaline-sensitive cyclic AMP accumulation."}
{"id": "PMID:210478", "title": "LSD and tryptamine effects on sleep/wakefulness and electrocorticogram patterns in intact cats.", "content": "Effects of intravenous infusions of LSD (3.75, 7.5, 15 microgram/kg over 5 min; crossover N = 4) and tryptamine (0.04, 0.08, 0.12 mg/kg/min for 150 min; crossover N = 6) were compared to saline in intact cats through observation of five sleep/waking patterns. Electrocorticogram (ECoG) was analyzed for frequency band indices and mean amplitude and frequency. LSD increases wakefulness and drowsiness and decreases spindle sleep and rapid eye movement (REM) sleep during the first 75 min (period 1). The increase in active wakefulness and decrease in REM sleep persist during period 2, with an increase in spindle sleep thereafter. LSD increases delta index and ECoG amplitude, with a decrease in ECoG frequency; these effects peaked in period 2. Tryptamine increases wakefulness and drowsiness during period 1, with decreases in spindle sleep and REM sleep. The increase in quiet wakefulness and decrease in REM sleep persist during period 2, but no significant tryptamine effect is seen in sleep/waking patterns after infusion ceases. ECoG frequency increases during tryptamine infusion (periods 1 and 2), while ECoG amplitude increases during periods 2 and 3. Thus LSD and tryptamine both increase wakefulness, decrease spindle sleep, and decrease REM sleep.", "contents": "LSD and tryptamine effects on sleep/wakefulness and electrocorticogram patterns in intact cats. Effects of intravenous infusions of LSD (3.75, 7.5, 15 microgram/kg over 5 min; crossover N = 4) and tryptamine (0.04, 0.08, 0.12 mg/kg/min for 150 min; crossover N = 6) were compared to saline in intact cats through observation of five sleep/waking patterns. Electrocorticogram (ECoG) was analyzed for frequency band indices and mean amplitude and frequency. LSD increases wakefulness and drowsiness and decreases spindle sleep and rapid eye movement (REM) sleep during the first 75 min (period 1). The increase in active wakefulness and decrease in REM sleep persist during period 2, with an increase in spindle sleep thereafter. LSD increases delta index and ECoG amplitude, with a decrease in ECoG frequency; these effects peaked in period 2. Tryptamine increases wakefulness and drowsiness during period 1, with decreases in spindle sleep and REM sleep. The increase in quiet wakefulness and decrease in REM sleep persist during period 2, but no significant tryptamine effect is seen in sleep/waking patterns after infusion ceases. ECoG frequency increases during tryptamine infusion (periods 1 and 2), while ECoG amplitude increases during periods 2 and 3. Thus LSD and tryptamine both increase wakefulness, decrease spindle sleep, and decrease REM sleep."}
{"id": "PMID:210479", "title": "Effects of L-tryptophan and ethanol on sleep parameters in the rat.", "content": "Sleep parameters were monitored following (1) a single 2 g/kg oral dose of ethanol, (2) an oral dose of L-tryptophan (600 mg/kg), and (3) administration of both drugs simultaneously. Ethanol reduced REM and increased slow wave significantly. The effects of L-tryptophan were apparent only in the case of one parameter, REM latency. Administration of both drugs resulted in a significantly shorter REM latency than that observed for ethanol alone. Results are discussed in terms of possible changes in the biosynthesis of 5-HT.", "contents": "Effects of L-tryptophan and ethanol on sleep parameters in the rat. Sleep parameters were monitored following (1) a single 2 g/kg oral dose of ethanol, (2) an oral dose of L-tryptophan (600 mg/kg), and (3) administration of both drugs simultaneously. Ethanol reduced REM and increased slow wave significantly. The effects of L-tryptophan were apparent only in the case of one parameter, REM latency. Administration of both drugs resulted in a significantly shorter REM latency than that observed for ethanol alone. Results are discussed in terms of possible changes in the biosynthesis of 5-HT."}
{"id": "PMID:210480", "title": "The effect of L-dopa and propranolol on human CSF cyclic nucleotides.", "content": "Human CSF cyclic AMP  and cyclic GMP have been measured as possible indicators of activity of central neurotransmitter-sensitive adenylate or guanylate cyclase. In an attempt to help to identify the specific neurotransmitter systems of origin of human CSF cyclic AMP and GMP, we studied Parkinson patients with and without L-dopa therapy and schizophrenic patients before and after propranolol therapy. No effect of L-dopa or propranolol was found on CSF cyclic nucleotides. However, Parkinson patients had a 40-50% reduction of CSF cyclic AMP and a 80-90% reduction of CSF cyclic GMP compared with the schizophrenic patients. Implications of this finding are discussed.", "contents": "The effect of L-dopa and propranolol on human CSF cyclic nucleotides. Human CSF cyclic AMP  and cyclic GMP have been measured as possible indicators of activity of central neurotransmitter-sensitive adenylate or guanylate cyclase. In an attempt to help to identify the specific neurotransmitter systems of origin of human CSF cyclic AMP and GMP, we studied Parkinson patients with and without L-dopa therapy and schizophrenic patients before and after propranolol therapy. No effect of L-dopa or propranolol was found on CSF cyclic nucleotides. However, Parkinson patients had a 40-50% reduction of CSF cyclic AMP and a 80-90% reduction of CSF cyclic GMP compared with the schizophrenic patients. Implications of this finding are discussed."}
{"id": "PMID:210481", "title": "[Insulinoma in the computer-tomogramm (author's transl)].", "content": "Documentation of insulinoma by computerized tomography and the diagnostic value of this new method compared with conventional radiography is discussed. The study of four cases demonstrates the capability of computer tomography to localize tumors in the pancreas.", "contents": "[Insulinoma in the computer-tomogramm (author's transl)]. Documentation of insulinoma by computerized tomography and the diagnostic value of this new method compared with conventional radiography is discussed. The study of four cases demonstrates the capability of computer tomography to localize tumors in the pancreas."}
{"id": "PMID:210484", "title": "Reduced adrenergic sensitivity in vivo in acute ethanol-fed rats.", "content": "Prior studies indicate ethanol feeding induces adrenergic subsensitivity in vitro, as measured by cyclic adenosine monophosphate  (cAMP) response of tissues to norepinephrine (NE). In this report we show acute ethanol feeding induces a depressed level of adrenergic sensitivity in vivo, as measured by plasma cAMP response to isoproterenol. Two hours after intragastric feeding of ethanol (6 gm/kg) to rats, there was a decrease in plasma cAMP response to intravenous isoproterenol, compared to dextrose controls. This decrease was the same in animals with blood ethanol levels averaging 68 mg/dl or 193 mg/dl. This data is consistent with the hypothesis that ethanol induces adrenergic subsensitivity.", "contents": "Reduced adrenergic sensitivity in vivo in acute ethanol-fed rats. Prior studies indicate ethanol feeding induces adrenergic subsensitivity in vitro, as measured by cyclic adenosine monophosphate  (cAMP) response of tissues to norepinephrine (NE). In this report we show acute ethanol feeding induces a depressed level of adrenergic sensitivity in vivo, as measured by plasma cAMP response to isoproterenol. Two hours after intragastric feeding of ethanol (6 gm/kg) to rats, there was a decrease in plasma cAMP response to intravenous isoproterenol, compared to dextrose controls. This decrease was the same in animals with blood ethanol levels averaging 68 mg/dl or 193 mg/dl. This data is consistent with the hypothesis that ethanol induces adrenergic subsensitivity."}
{"id": "PMID:210485", "title": "Effect of somatostatin analogues and 17-alpha-dihydroequilin on rat brain opiate receptors.", "content": "Two somatostatin analogues (SA)  and 17-alpha-dihydroequilin (E) inhibited the stereospecific binding of 3H-naloxone in vitro to rat brain opiate receptors in the absence of sodium. The addition of sodium indicated the SA to be greater or similar in potency to somatostatin as opiate agonists and E to be an opiate antagonist. The results indicate that SA and certain steroids may affect endorphin containing neurons.", "contents": "Effect of somatostatin analogues and 17-alpha-dihydroequilin on rat brain opiate receptors. Two somatostatin analogues (SA)  and 17-alpha-dihydroequilin (E) inhibited the stereospecific binding of 3H-naloxone in vitro to rat brain opiate receptors in the absence of sodium. The addition of sodium indicated the SA to be greater or similar in potency to somatostatin as opiate agonists and E to be an opiate antagonist. The results indicate that SA and certain steroids may affect endorphin containing neurons."}
{"id": "PMID:210486", "title": "Inducing of automatism of Purkinje fibers with dibutyryl 3', 5' cyclic AMP.", "content": "Dibutyryl 3', 5'-cyclic AMP induced automatic activity in Purkinje fibers of myocardial strip in the rat. The phenomenon was not affected by beta adrenergic blockade.", "contents": "Inducing of automatism of Purkinje fibers with dibutyryl 3', 5' cyclic AMP. Dibutyryl 3', 5'-cyclic AMP induced automatic activity in Purkinje fibers of myocardial strip in the rat. The phenomenon was not affected by beta adrenergic blockade."}
{"id": "PMID:210487", "title": "[Parameters of collagen biosynthesis in cotton pellet granuloma of rats on iron deficiency (author's transl)].", "content": "Rats of Wistar strain, of same age, were kept on iron free diet up to nearly absolute iron deficiency in iron depots. Afterwards granuloma was produced by implantation of cotton pellets subcutaneously. For characterization of the collagen biosynthesis in the granuloma the neutral salt soluble collagen and the activity of the prolyl hydroxylase were measured in the granuloma 4, 8 and 12 days after cotton pellet implantation. At the same time \"collagen-like\" protein was determined in the serum of the animals. The enzyme activity was statistically significant lower in the granuloma of animals on iron deficiency than in the granuloma of the comparable groups on normal diet. Statistically significant higher concentration of neutral salt soluble collagen was found 8 and 12 days after cotton pellet implantation in the group on iron free diet. There was no significant difference as to the serum levels of \"collagen-like\" protein in serum.", "contents": "[Parameters of collagen biosynthesis in cotton pellet granuloma of rats on iron deficiency (author's transl)]. Rats of Wistar strain, of same age, were kept on iron free diet up to nearly absolute iron deficiency in iron depots. Afterwards granuloma was produced by implantation of cotton pellets subcutaneously. For characterization of the collagen biosynthesis in the granuloma the neutral salt soluble collagen and the activity of the prolyl hydroxylase were measured in the granuloma 4, 8 and 12 days after cotton pellet implantation. At the same time \"collagen-like\" protein was determined in the serum of the animals. The enzyme activity was statistically significant lower in the granuloma of animals on iron deficiency than in the granuloma of the comparable groups on normal diet. Statistically significant higher concentration of neutral salt soluble collagen was found 8 and 12 days after cotton pellet implantation in the group on iron free diet. There was no significant difference as to the serum levels of \"collagen-like\" protein in serum."}
{"id": "PMID:210489", "title": "Peroxidase activity in human granulocytes, inter- and intra-individual variations.", "content": "A kinetic method for quantitation of peroxidase activity ('myeloperoxidase', E.C. 1.11.1.7.) in human granulocytes has been evaluated. The enzymic activity was determined at 37 degrees C, PH = 7.0. Substrates: 2-methyxo-phenol (1.25 mmol/l) and H2O2 (0.1 mmol/l). When applied on granulocytes from solitary blood samples from healthy, normal subjects the detected peroxidase activity varied considerably from one person to another (CV = 40-50%). Sequential determinations of the peroxidase activity in granulocytes from selected healthy, normal subjects demonstrated substantial intra-individual variations. Analysis of variance confirmed that the intra-individual variations (CV = 36%) exceeded all other variance components involved.", "contents": "Peroxidase activity in human granulocytes, inter- and intra-individual variations. A kinetic method for quantitation of peroxidase activity ('myeloperoxidase', E.C. 1.11.1.7.) in human granulocytes has been evaluated. The enzymic activity was determined at 37 degrees C, PH = 7.0. Substrates: 2-methyxo-phenol (1.25 mmol/l) and H2O2 (0.1 mmol/l). When applied on granulocytes from solitary blood samples from healthy, normal subjects the detected peroxidase activity varied considerably from one person to another (CV = 40-50%). Sequential determinations of the peroxidase activity in granulocytes from selected healthy, normal subjects demonstrated substantial intra-individual variations. Analysis of variance confirmed that the intra-individual variations (CV = 36%) exceeded all other variance components involved."}
{"id": "PMID:210490", "title": "Studies on the pre-alpha-lipoprotein of human serum. I. characterization of an albumin-containing lipoprotein.", "content": "In this study an albumin-containing lipoprotein is isolated by column affinity chromatography and electrophoresis. Its electrophoretic mobility is faster than that of albumin in agarose gel. Immunologically it reacts with anti-albumin and anti-apolipoprotein-A-I. No reaction is obtained against antibodies to any of the other previously known lipoportein families: Apo-AII, Apo-B, Lp(a), Apo-C, LpX, Apo-D or Apo-E ('the arginine rich peptide'). It differs from purified albumin in having higher amounts of glycine, serine and glutamic acid. Moreover, the molecular weight is estimated to 80,000 as compared to 67,000 for albumin.", "contents": "Studies on the pre-alpha-lipoprotein of human serum. I. characterization of an albumin-containing lipoprotein. In this study an albumin-containing lipoprotein is isolated by column affinity chromatography and electrophoresis. Its electrophoretic mobility is faster than that of albumin in agarose gel. Immunologically it reacts with anti-albumin and anti-apolipoprotein-A-I. No reaction is obtained against antibodies to any of the other previously known lipoportein families: Apo-AII, Apo-B, Lp(a), Apo-C, LpX, Apo-D or Apo-E ('the arginine rich peptide'). It differs from purified albumin in having higher amounts of glycine, serine and glutamic acid. Moreover, the molecular weight is estimated to 80,000 as compared to 67,000 for albumin."}
{"id": "PMID:210492", "title": "Effects of corticotrophin and choriogonadotrophin on urinary cyclic adenosine 3',5'-monophosphate.", "content": "The actions of exogenous corticotrophin (ACTH) and human choriogonadotrophin (HCG) were assessed by measuring cyclic adenosine 3',5'-monophosphate (cAMP), 17-ketosteroids (17-KS), 17-ketogenic steroids (17-KGS), androsterone (A), etiocholanolone (E), dehydroepiandrosterone (DHEA) and pregnanetriol (P3) in 24 h urine. ACTH was infused intravenously into six healthy women. A dexamethasone (DXM) suppression test was also performed, and continued when HCG was injected intramuscularly. The effects of intramuscular injection of ACTH and administration of DXM on urinary cAMP, 17-KS and 17-KGS were also studied in an adrenalectomized and ovariectomized patient. ACTH, 250 microgram (25 i.u.), increased excretion of cAMP in the healthy women and also in the patient. In the six controls there was a simultaneous normal increase in 17-KS, 17-KGS, A, E, DHEA and P3 excretion. DXM did not cause the excretion of cAMP to fall below the basal level in any of the subjects examined but the excretion of all the steroids studied decreased significantly. The only effect of HCG was to increase P3 excretion. The results indicate that the increment in cAMP is probably related to an extra-adrenal effect regulated by ACTH.", "contents": "Effects of corticotrophin and choriogonadotrophin on urinary cyclic adenosine 3',5'-monophosphate. The actions of exogenous corticotrophin (ACTH) and human choriogonadotrophin (HCG) were assessed by measuring cyclic adenosine 3',5'-monophosphate (cAMP), 17-ketosteroids (17-KS), 17-ketogenic steroids (17-KGS), androsterone (A), etiocholanolone (E), dehydroepiandrosterone (DHEA) and pregnanetriol (P3) in 24 h urine. ACTH was infused intravenously into six healthy women. A dexamethasone (DXM) suppression test was also performed, and continued when HCG was injected intramuscularly. The effects of intramuscular injection of ACTH and administration of DXM on urinary cAMP, 17-KS and 17-KGS were also studied in an adrenalectomized and ovariectomized patient. ACTH, 250 microgram (25 i.u.), increased excretion of cAMP in the healthy women and also in the patient. In the six controls there was a simultaneous normal increase in 17-KS, 17-KGS, A, E, DHEA and P3 excretion. DXM did not cause the excretion of cAMP to fall below the basal level in any of the subjects examined but the excretion of all the steroids studied decreased significantly. The only effect of HCG was to increase P3 excretion. The results indicate that the increment in cAMP is probably related to an extra-adrenal effect regulated by ACTH."}
{"id": "PMID:210493", "title": "High density lipoproteins (HDL) and physical activity: the influence of physical exercise, age and smoking on HDL-cholesterol and the HDL-/total cholesterol ratio.", "content": "220 trained men, examined the day before participation in a cross country ski-race, had significantly higher HDL-cholesterol and HDL-/total cholesterol ratio than untrained men, but did not differ signficantly from untrained women. HDL-cholesterol was significantly higher in skiers above 60 years than in skiers of younger age. Tobacco smokers ahd lower HDL-cholesterol and HDL-/total cholesterol ratio than non-smokers, but the differences were only significant in skiers, not in controls. HDL-cholesterol was positively correlated to total cholesterol in skiers. The HDL-cholesterol level may possibly contribute to the lower morbidity of CHD in men who are physically active during leisure time.", "contents": "High density lipoproteins (HDL) and physical activity: the influence of physical exercise, age and smoking on HDL-cholesterol and the HDL-/total cholesterol ratio. 220 trained men, examined the day before participation in a cross country ski-race, had significantly higher HDL-cholesterol and HDL-/total cholesterol ratio than untrained men, but did not differ signficantly from untrained women. HDL-cholesterol was significantly higher in skiers above 60 years than in skiers of younger age. Tobacco smokers ahd lower HDL-cholesterol and HDL-/total cholesterol ratio than non-smokers, but the differences were only significant in skiers, not in controls. HDL-cholesterol was positively correlated to total cholesterol in skiers. The HDL-cholesterol level may possibly contribute to the lower morbidity of CHD in men who are physically active during leisure time."}
{"id": "PMID:210494", "title": "Comparison of the reactions of neutral granulocyte proteases with the major plasma protease inhibitors and with antiplasmin.", "content": "Reaction mixtures of human serum and increasing amounts of granulocyte collagenase, elastase and chymotrypsin-like enzyme were studied by crossed immunoelectrophoresis utilizing antibodies against alpha1-antitrypsin, alpha1-antichymotrypsin, and antiplasmin. The increasing complex formation of alpha1-antitrypsin and alpha 1-antichymotrypsin with the different granulocyte proteases was not accompanied by any changes in the electrophoretic mobility or precipitate pattern of antiplasmin until the protease binding capacity of serum was saturated. The antiplasmin component in the reaction mixtures of human serum and granulocyte collagenase or elastase was not precipitated by antibodies against the proteases. The results indicate that none of the granulocyte proteases are bound by antiplasmin and that these enzymes do not activate plasminogen in serum.", "contents": "Comparison of the reactions of neutral granulocyte proteases with the major plasma protease inhibitors and with antiplasmin. Reaction mixtures of human serum and increasing amounts of granulocyte collagenase, elastase and chymotrypsin-like enzyme were studied by crossed immunoelectrophoresis utilizing antibodies against alpha1-antitrypsin, alpha1-antichymotrypsin, and antiplasmin. The increasing complex formation of alpha1-antitrypsin and alpha 1-antichymotrypsin with the different granulocyte proteases was not accompanied by any changes in the electrophoretic mobility or precipitate pattern of antiplasmin until the protease binding capacity of serum was saturated. The antiplasmin component in the reaction mixtures of human serum and granulocyte collagenase or elastase was not precipitated by antibodies against the proteases. The results indicate that none of the granulocyte proteases are bound by antiplasmin and that these enzymes do not activate plasminogen in serum."}
{"id": "PMID:210495", "title": "Studies on the pre-alpha-lipoprotein of human serum. II. Evidence for the presence of an albumin-apo-A-I complex.", "content": "By combined column affinity chromatography and preparative electrophoresis, a lipoprotein was isolated from the electrophoretically defined pre-alpha-region. The isolated fraction, designated Fraction II1, demonstrated one band after electrophoresis in agarose, in polyacrylamide, and in sodium dodecylsulphate containing polyacrylamid. Double diffusion experiments disclosed the presence of albumin and apolipoprotein-A-I within the fraction. After reduction with mercaptoethanol and subsequent electrophoresis in sodium dodecylsulphate containing polyacrylamide gel, two bands appeared. One of the bands had an electrophoretic mobility similar to albumin monomer (mol.wt 67,000), the other had the same electrophoretic mobility as apolipoprotein-A-I with a mol.wt of 28,400. It is suggested that Fraction II1 contains an albumin-apolipoprotein-A-I complex.", "contents": "Studies on the pre-alpha-lipoprotein of human serum. II. Evidence for the presence of an albumin-apo-A-I complex. By combined column affinity chromatography and preparative electrophoresis, a lipoprotein was isolated from the electrophoretically defined pre-alpha-region. The isolated fraction, designated Fraction II1, demonstrated one band after electrophoresis in agarose, in polyacrylamide, and in sodium dodecylsulphate containing polyacrylamid. Double diffusion experiments disclosed the presence of albumin and apolipoprotein-A-I within the fraction. After reduction with mercaptoethanol and subsequent electrophoresis in sodium dodecylsulphate containing polyacrylamide gel, two bands appeared. One of the bands had an electrophoretic mobility similar to albumin monomer (mol.wt 67,000), the other had the same electrophoretic mobility as apolipoprotein-A-I with a mol.wt of 28,400. It is suggested that Fraction II1 contains an albumin-apolipoprotein-A-I complex."}
{"id": "PMID:210496", "title": "Adenylate cyclase activity in human liver membranes and its inhibition by adenosine and adenine nucleotides.", "content": "The production of adenosine 3',5'-monophosphate (cyclic AMP) in a membrane preparation from human liver homogenate has been studied. Cyclic AMP production was enhanced by glucagon, guanylyl 5'-imidodiphosphate (GMP-PNP), or fluoride, or combinations of these. Adenosine, adenosine monophosphate (AMP) and adenosine diphosphate (ADP) at a concentration of 10(-3) mol/l antagonized the effects of all stimulants. These data suggest that inhibitory effects are exercised at the catalytic moiety of the adenylate cyclase system, or at the transducer function between hormone receptor and catalytic unit. In contrast, adenosine at a concentration of 10(-5) mol/l antagonized glucagon- but not fluoride-stimulated adenylate cyclase activity.", "contents": "Adenylate cyclase activity in human liver membranes and its inhibition by adenosine and adenine nucleotides. The production of adenosine 3',5'-monophosphate (cyclic AMP) in a membrane preparation from human liver homogenate has been studied. Cyclic AMP production was enhanced by glucagon, guanylyl 5'-imidodiphosphate (GMP-PNP), or fluoride, or combinations of these. Adenosine, adenosine monophosphate (AMP) and adenosine diphosphate (ADP) at a concentration of 10(-3) mol/l antagonized the effects of all stimulants. These data suggest that inhibitory effects are exercised at the catalytic moiety of the adenylate cyclase system, or at the transducer function between hormone receptor and catalytic unit. In contrast, adenosine at a concentration of 10(-5) mol/l antagonized glucagon- but not fluoride-stimulated adenylate cyclase activity."}
{"id": "PMID:210497", "title": "Muscle metabolism during and after strenuous intermittent running.", "content": "Muscle and blood metabolites, plasma insulin and cyclic adenosine 3',5'-monophosphate (cAMP) levels were investigated in five male runners before and after strenuous intermittent running exercise of short duration. Immediately after the exercise, the mean muscle creatine phosphate level (CrP) had fallen by 74% (P less than 0.02) and 30 min later the initial level was regained in only one subject. Other immediate results were increases in mean muscle lactate (460%, P less than 0.005), glucose (130%), glucose-6-phosphate (G6P, 320%) and fructose-1,6-diphosphate (FDP, 32%). Muscle ATP and glycogen concentration had decreased by 31 and 23% (P less than 0.05), respectively. However, ATP, glucose, G6P and FDP changes were not significant owing to the great individual variation. This may have been due to the different training programmes of the runners. Immediately after the exercise mean plasma insulin was 210% (P less than 0.01), blood glucose 71% (P less than 0.005) and plasma cAMP concentration 260% (P less than 0.01) higher than the pre-exercise values. After running urinary excretion of cAMP was 29% higher than before the exercise. It is concluded that exhaustive, short-term exercise activates the liver adenylate cyclase system so giving rise to an increased level of blood glucose, which is an important source of energy during this type of exercise.", "contents": "Muscle metabolism during and after strenuous intermittent running. Muscle and blood metabolites, plasma insulin and cyclic adenosine 3',5'-monophosphate (cAMP) levels were investigated in five male runners before and after strenuous intermittent running exercise of short duration. Immediately after the exercise, the mean muscle creatine phosphate level (CrP) had fallen by 74% (P less than 0.02) and 30 min later the initial level was regained in only one subject. Other immediate results were increases in mean muscle lactate (460%, P less than 0.005), glucose (130%), glucose-6-phosphate (G6P, 320%) and fructose-1,6-diphosphate (FDP, 32%). Muscle ATP and glycogen concentration had decreased by 31 and 23% (P less than 0.05), respectively. However, ATP, glucose, G6P and FDP changes were not significant owing to the great individual variation. This may have been due to the different training programmes of the runners. Immediately after the exercise mean plasma insulin was 210% (P less than 0.01), blood glucose 71% (P less than 0.005) and plasma cAMP concentration 260% (P less than 0.01) higher than the pre-exercise values. After running urinary excretion of cAMP was 29% higher than before the exercise. It is concluded that exhaustive, short-term exercise activates the liver adenylate cyclase system so giving rise to an increased level of blood glucose, which is an important source of energy during this type of exercise."}
{"id": "PMID:210498", "title": "Multiple sclerosis: local synthesis of electrophoretically restricted measles, rubella, mumps and herpes simplex virus antibodies in the central nervous system.", "content": "An imprint electroimmunofixation (IEIF) technique was used to study measles, rubella, mumps and herpes simplex virus antibodies in serum and concentrated cerebrospinal fluid (CSF) from ten patients with multiple sclerosis (MS). Electrophoretically restricted virus-specific antibodies were detected in sera or CSF from nine of the ten patients. Comparison of the antibody patterns in matching serum and CSF samples indicated that electrophoretically restricted populations of antibody against one or more of the four viruses were produced locally in the central nervous system of nine patients. No association between the locally produced antibody populations the oligoclonal IgG of the CSF could be demonstrated. The virus-specific antibodies studied thus seem to constitute only a minor fraction of the total IgG of the CSF from MS patients.", "contents": "Multiple sclerosis: local synthesis of electrophoretically restricted measles, rubella, mumps and herpes simplex virus antibodies in the central nervous system. An imprint electroimmunofixation (IEIF) technique was used to study measles, rubella, mumps and herpes simplex virus antibodies in serum and concentrated cerebrospinal fluid (CSF) from ten patients with multiple sclerosis (MS). Electrophoretically restricted virus-specific antibodies were detected in sera or CSF from nine of the ten patients. Comparison of the antibody patterns in matching serum and CSF samples indicated that electrophoretically restricted populations of antibody against one or more of the four viruses were produced locally in the central nervous system of nine patients. No association between the locally produced antibody populations the oligoclonal IgG of the CSF could be demonstrated. The virus-specific antibodies studied thus seem to constitute only a minor fraction of the total IgG of the CSF from MS patients."}
{"id": "PMID:210499", "title": "[The state of hormone and chemotherapy in breast neoplasms].", "content": "Several decisive developments have emerged during the past few years in the hormonal treatment and chemotherapy receptors should make for a more selective and successful application of hormone therapy. In the field of chemotherapy, highly active substances have been developed. Two groups of routine treatment may be defined: the first employs combinations of cytoxan, methotrexate, 5-fluorouracil and prednisone, and the other, combinations of these agents with the highly active adriamycin. With these combinations, remissions lasting an average of over one year, with significantly prolonged survival, can be achieved in about two thirds of patients. It remains uncertain whether initial addition of hormone treatment to the chemotherapy is of definite advantage. Modern chemotherapy appears to have been especially beneficial in altering the course in patients with poor prognosis. The newest development is the use of chemotherapy postoperatively, i.e. so-called adjuvant chemotherapy. For the present this should only be done within controlled studies and in patients with histologically proven axillary lymph node metastases.", "contents": "[The state of hormone and chemotherapy in breast neoplasms]. Several decisive developments have emerged during the past few years in the hormonal treatment and chemotherapy receptors should make for a more selective and successful application of hormone therapy. In the field of chemotherapy, highly active substances have been developed. Two groups of routine treatment may be defined: the first employs combinations of cytoxan, methotrexate, 5-fluorouracil and prednisone, and the other, combinations of these agents with the highly active adriamycin. With these combinations, remissions lasting an average of over one year, with significantly prolonged survival, can be achieved in about two thirds of patients. It remains uncertain whether initial addition of hormone treatment to the chemotherapy is of definite advantage. Modern chemotherapy appears to have been especially beneficial in altering the course in patients with poor prognosis. The newest development is the use of chemotherapy postoperatively, i.e. so-called adjuvant chemotherapy. For the present this should only be done within controlled studies and in patients with histologically proven axillary lymph node metastases."}
{"id": "PMID:210500", "title": "Trisodium phosphonoformate, a new antiviral compound.", "content": "Trisodium phosphonoformate selectively inhibits cell-free DNA polymerase activity induced by herpesvirus. The new inhibitor has an antiviral effect on herpes simplex virus types 1 and 2, pseudorables virus, and infectious bovine rhinotracheitis virus in cell culture. It has a good therapeutic activity against cutaneous herpes simplex virus infection in guinea pigs.", "contents": "Trisodium phosphonoformate, a new antiviral compound. Trisodium phosphonoformate selectively inhibits cell-free DNA polymerase activity induced by herpesvirus. The new inhibitor has an antiviral effect on herpes simplex virus types 1 and 2, pseudorables virus, and infectious bovine rhinotracheitis virus in cell culture. It has a good therapeutic activity against cutaneous herpes simplex virus infection in guinea pigs."}
{"id": "PMID:210501", "title": "Generation of new mouse sarcoma viruses in cell culture.", "content": "Endogenous nontumor-producing type C viruses from C3H mice were used to generate rapid, solid tumor-inducing variants in cell culture. The new mouse sarcoma viruses induce undifferentiated sarcomas with a short latency period upon inoculation into newborn NIH Swiss mice. Transforming viruses appear only transiently, at a time when the virus-infected cells show morphologic alterations; both before and after this time, transforming viruses cannot be detected. These results show that variants of endogenous type C virus which contain transforming genes (oncogenes) can arise during spread of the endogenous virus in fibroblast lines in vitro as well as in susceptible tissues in vivo.", "contents": "Generation of new mouse sarcoma viruses in cell culture. Endogenous nontumor-producing type C viruses from C3H mice were used to generate rapid, solid tumor-inducing variants in cell culture. The new mouse sarcoma viruses induce undifferentiated sarcomas with a short latency period upon inoculation into newborn NIH Swiss mice. Transforming viruses appear only transiently, at a time when the virus-infected cells show morphologic alterations; both before and after this time, transforming viruses cannot be detected. These results show that variants of endogenous type C virus which contain transforming genes (oncogenes) can arise during spread of the endogenous virus in fibroblast lines in vitro as well as in susceptible tissues in vivo."}
{"id": "PMID:210502", "title": "Growth inhibition of transformed cells with succinylated concanavalin A.", "content": "Succinylated concanavalin A reversibly inhibits the growth of SV40 transformed mouse 3T3 cells and thus causes an accumulation of the cells in the G1 phase of the cell cycle. In a soft substrate (methylcellulose) succinylated concanavalin A also restores in transformed cells the growth behavior typical of untransformed cells.", "contents": "Growth inhibition of transformed cells with succinylated concanavalin A. Succinylated concanavalin A reversibly inhibits the growth of SV40 transformed mouse 3T3 cells and thus causes an accumulation of the cells in the G1 phase of the cell cycle. In a soft substrate (methylcellulose) succinylated concanavalin A also restores in transformed cells the growth behavior typical of untransformed cells."}
{"id": "PMID:210503", "title": "Cytidine 3',5'-monophosphate phosphodiesterase: decreased activity in the regenerating and developing liver.", "content": "A decrease in the activity of the enzyme cytidine 3',5'-monophosphate (cyclic CMP) phosphodiesterase was noted in the regenerating liver of young rats as early as 8 hours after partial hepatectomy, with a maximum decrease occurring 12 hours after the surgery. In comparison, in old rats which showed a slower liver growth, the maximum decrease in the activity of cyclic CMP phosphodiesterase was smaller and occurred at a much later time (2 days after surgery). A similar decrease in the enzyme activity was observed in the fetal liver of guinea pigs. These findings suggest that regulation of tissue concentration of cyclic CMP may be crucial for the regeneration and development of the liver.", "contents": "Cytidine 3',5'-monophosphate phosphodiesterase: decreased activity in the regenerating and developing liver. A decrease in the activity of the enzyme cytidine 3',5'-monophosphate (cyclic CMP) phosphodiesterase was noted in the regenerating liver of young rats as early as 8 hours after partial hepatectomy, with a maximum decrease occurring 12 hours after the surgery. In comparison, in old rats which showed a slower liver growth, the maximum decrease in the activity of cyclic CMP phosphodiesterase was smaller and occurred at a much later time (2 days after surgery). A similar decrease in the enzyme activity was observed in the fetal liver of guinea pigs. These findings suggest that regulation of tissue concentration of cyclic CMP may be crucial for the regeneration and development of the liver."}
{"id": "PMID:210504", "title": "The biology of oxygen radicals.", "content": "The reactive superoxide radical, O2-, formerly of concern only to radiation chemists and radiobiologists, is now understood to be a normal product of the biological reduction of molecular oxygen. An unusual family of enzymes, the superoxide dismutases, protect against the deleterious actions of this radical by catalyzing its dismutation to hydrogen peroxide plus oxygen.", "contents": "The biology of oxygen radicals. The reactive superoxide radical, O2-, formerly of concern only to radiation chemists and radiobiologists, is now understood to be a normal product of the biological reduction of molecular oxygen. An unusual family of enzymes, the superoxide dismutases, protect against the deleterious actions of this radical by catalyzing its dismutation to hydrogen peroxide plus oxygen."}
{"id": "PMID:210506", "title": "Opiate effects after adrenocorticotropin or beta-endorphin injection in the periaqueductal gray matter of rats.", "content": "Injections of adrenocorticotropic hormone (ACTH) into the periaqueductal gray matter of drug-naive rats resulted in a dose-dependent opiate abstinence syndrome characterized by fearful hyperreactivity and explosive motor behavior. Injecting shorter chains of ACTH caused attenuated forms of this behavior. Injections of beta-endorphin at this same site caused opposite behavior: sedative, analgestic, and catatonic. If the effects of morphine are mediated by two classes of receptor) and the other which is not stereospecific and naloxone-insensitive--the endogtor)--and the other which is not stereospecific and naloxone-insensitive the endogenous ligand of the second receptor may be ACTH. The neuropeptides ACTH and endorphin may be part of an integrated neuromodulatory system, and the opiate abstinence syndrome may be the result of an altered interaction between the two receptor systems.", "contents": "Opiate effects after adrenocorticotropin or beta-endorphin injection in the periaqueductal gray matter of rats. Injections of adrenocorticotropic hormone (ACTH) into the periaqueductal gray matter of drug-naive rats resulted in a dose-dependent opiate abstinence syndrome characterized by fearful hyperreactivity and explosive motor behavior. Injecting shorter chains of ACTH caused attenuated forms of this behavior. Injections of beta-endorphin at this same site caused opposite behavior: sedative, analgestic, and catatonic. If the effects of morphine are mediated by two classes of receptor) and the other which is not stereospecific and naloxone-insensitive--the endogtor)--and the other which is not stereospecific and naloxone-insensitive the endogenous ligand of the second receptor may be ACTH. The neuropeptides ACTH and endorphin may be part of an integrated neuromodulatory system, and the opiate abstinence syndrome may be the result of an altered interaction between the two receptor systems."}
{"id": "PMID:210508", "title": "Rod-cone dysplasia in Irish setters: a defect in cyclic GMP metabolism in visual cells.", "content": "An abnormality in retinal guanosine 3,5-monophosphate (cyclic GMP) metabolism is demonstrated in the inherited rod-cone dysplasis of Irish Setter dogs. Affected visual cells are deficient in cyclic GMP phosphodiesterase activity and have elevated levels of cyclic GMP. The biochemical abnormalities observed in affected retinas of Irish Setters are similar to those in the retinas of mice with inherited retinal degeneration before visual cell degeneration begins. A defect in cyclic GMP metabolism may be characteristic of early-onset degenerative diseases of the retina, possibly including those that affect humans.", "contents": "Rod-cone dysplasia in Irish setters: a defect in cyclic GMP metabolism in visual cells. An abnormality in retinal guanosine 3,5-monophosphate (cyclic GMP) metabolism is demonstrated in the inherited rod-cone dysplasis of Irish Setter dogs. Affected visual cells are deficient in cyclic GMP phosphodiesterase activity and have elevated levels of cyclic GMP. The biochemical abnormalities observed in affected retinas of Irish Setters are similar to those in the retinas of mice with inherited retinal degeneration before visual cell degeneration begins. A defect in cyclic GMP metabolism may be characteristic of early-onset degenerative diseases of the retina, possibly including those that affect humans."}
{"id": "PMID:210507", "title": "Mitochondrial thyroid hormone receptor: localization and physiological significance.", "content": "Binding studies of thyroid hormone to submitochondrial fractions from rat liver suggest that the component responsible for high-affinity, low-capacity (saturable) binding of hormones arises from the inner mitochondrial membrane. The partially purified component, approximately 150,000 daltons, appears to be half protein and half lipid, largely phospholipids, tentatively identified as lecithin, phosphatidyl ethanolamine, and cardiolipin. A similar hormone-binding macromolecule was found in mitochondria from rabbit kidney, from human liver and kidney, and from rat kidney, myocardium, skeletal muscle, intestinal mucosa, whole small intestine, adipose tissue, and lung. It was absent from mitochondria of adult rat brain, spleen, and testis, organs calorigenically unresponsive to thyroid hormones injected in vivo, but was present in mitochondria from brains of rats 12 days old and younger. The organ distribution of the hormone-binding protein and its presence in neonatal brain mitochondria supports the biological relevance of the mitochondrial component as a thyroid hormone receptor.", "contents": "Mitochondrial thyroid hormone receptor: localization and physiological significance. Binding studies of thyroid hormone to submitochondrial fractions from rat liver suggest that the component responsible for high-affinity, low-capacity (saturable) binding of hormones arises from the inner mitochondrial membrane. The partially purified component, approximately 150,000 daltons, appears to be half protein and half lipid, largely phospholipids, tentatively identified as lecithin, phosphatidyl ethanolamine, and cardiolipin. A similar hormone-binding macromolecule was found in mitochondria from rabbit kidney, from human liver and kidney, and from rat kidney, myocardium, skeletal muscle, intestinal mucosa, whole small intestine, adipose tissue, and lung. It was absent from mitochondria of adult rat brain, spleen, and testis, organs calorigenically unresponsive to thyroid hormones injected in vivo, but was present in mitochondria from brains of rats 12 days old and younger. The organ distribution of the hormone-binding protein and its presence in neonatal brain mitochondria supports the biological relevance of the mitochondrial component as a thyroid hormone receptor."}
{"id": "PMID:210509", "title": "[Pulmonary embolism in general medicine. Characteristics and diagnostic elements].", "content": "Natural history of pulmonary embolism observed during a 4-year period in a non-discriminayory Department of Internal Medicine, with reference to 7,843 admissions : 2 per cent of patients, 9 per cent of deaths, 22 per cent of post-mortem examinations. Value of various paraclinical examinations, more especially ECG, lung scintigraphy and determination of blood gases.", "contents": "[Pulmonary embolism in general medicine. Characteristics and diagnostic elements]. Natural history of pulmonary embolism observed during a 4-year period in a non-discriminayory Department of Internal Medicine, with reference to 7,843 admissions : 2 per cent of patients, 9 per cent of deaths, 22 per cent of post-mortem examinations. Value of various paraclinical examinations, more especially ECG, lung scintigraphy and determination of blood gases."}
{"id": "PMID:210510", "title": "[A simple evaluation of osteoporosis: study of the architecture of the upper extremity of the femur by pelvic radiography].", "content": "From the study of the architectural features of the system connecting the neck to the femoral diaphysis on pelvic radio-grams, osteoporosis can be classified into seven stages (7 to 1) of increasing severity. It is thus possible to estimate the risk of fracture, the latter being over 50 per cent from stage 4 onward. The cortex-diaphysis relationship (RCD) follows a parallel course but is less reliable. The investigation of a control group of 20 subjects and 37 patients with osteoporosis, aged 50 to over 80, shows the value of this method, with which it is moreover possible to check the evolution of the disease and the effects of treatment.", "contents": "[A simple evaluation of osteoporosis: study of the architecture of the upper extremity of the femur by pelvic radiography]. From the study of the architectural features of the system connecting the neck to the femoral diaphysis on pelvic radio-grams, osteoporosis can be classified into seven stages (7 to 1) of increasing severity. It is thus possible to estimate the risk of fracture, the latter being over 50 per cent from stage 4 onward. The cortex-diaphysis relationship (RCD) follows a parallel course but is less reliable. The investigation of a control group of 20 subjects and 37 patients with osteoporosis, aged 50 to over 80, shows the value of this method, with which it is moreover possible to check the evolution of the disease and the effects of treatment."}
{"id": "PMID:210511", "title": "[The heart of the nonagenarian].", "content": "Clinical, radiological and electrocardiographic abnormalities found at cardiovascular examination of 140 patients in their nineties admitted into hospital, were listed and a systematic comparison was established between 36 subjects in their nineties in a home for the aged and subjects in their eighties in the same home. Comparison with previous similar series.", "contents": "[The heart of the nonagenarian]. Clinical, radiological and electrocardiographic abnormalities found at cardiovascular examination of 140 patients in their nineties admitted into hospital, were listed and a systematic comparison was established between 36 subjects in their nineties in a home for the aged and subjects in their eighties in the same home. Comparison with previous similar series."}
{"id": "PMID:210512", "title": "[Effect of tiapride on the side effects of cerebrospinal fluid depletions in spinal puncture, pneumoencephalography and air myelography].", "content": "The authors report their experience of the treatment post-cerebrospinal fluid loss syndrom, following subtraction by lumbar puncture, pneumoencephalography and air myelography. The study of 70 patients, divided in two equal groups, one receiving classic therapy, one receiving tiapride, a new molecule of original conception, lead to emphasize the interest of this drug. Tolerance in general is good, despite the administration of high doses and effects on the syndrom are positive and remarkable in preventive and curative treatment.", "contents": "[Effect of tiapride on the side effects of cerebrospinal fluid depletions in spinal puncture, pneumoencephalography and air myelography]. The authors report their experience of the treatment post-cerebrospinal fluid loss syndrom, following subtraction by lumbar puncture, pneumoencephalography and air myelography. The study of 70 patients, divided in two equal groups, one receiving classic therapy, one receiving tiapride, a new molecule of original conception, lead to emphasize the interest of this drug. Tolerance in general is good, despite the administration of high doses and effects on the syndrom are positive and remarkable in preventive and curative treatment."}
{"id": "PMID:210514", "title": "[Vascular manifestations of Touraine's great aphtosis (Behcet's syndrome)].", "content": "Among the systemic manifestations of Beh\u00e7et's syndrome, venous and arterial involvements are discussed. Venous thrombosis is a common manifestation and may be considered as a cardinal sign in the diagnosis. Venous and arterial thrombotic complications may be regarded as agents of morbidity and mortality. The pathogenesis of the occlusive process is still some what obscure, although vasculitis and impaired local vascular fibrinolytic activity play a part in it. Therapeutic measures using fibrinolytic enhancing agents may prevent and control the thrombotic complications of the disease.", "contents": "[Vascular manifestations of Touraine's great aphtosis (Behcet's syndrome)]. Among the systemic manifestations of Beh\u00e7et's syndrome, venous and arterial involvements are discussed. Venous thrombosis is a common manifestation and may be considered as a cardinal sign in the diagnosis. Venous and arterial thrombotic complications may be regarded as agents of morbidity and mortality. The pathogenesis of the occlusive process is still some what obscure, although vasculitis and impaired local vascular fibrinolytic activity play a part in it. Therapeutic measures using fibrinolytic enhancing agents may prevent and control the thrombotic complications of the disease."}
{"id": "PMID:210515", "title": "[Frequency of association of cardiac and urinary abnormalities].", "content": "In 680 cases of congenital heart disease, the authors discovered 49 uropathies (i.e. 7.2%) diagnosed thanks to a film of the urinary apparatus taken during angiocardiography. These uropathies were encountered mainly during ventricular septal defects, pulmonary stenosis and Fallot's tetralogy. The diagnostic value of the film during angiocardiography is great as it revealed 22 out of 49 uropathies (i.e. 44.9%) clinically silent until then.", "contents": "[Frequency of association of cardiac and urinary abnormalities]. In 680 cases of congenital heart disease, the authors discovered 49 uropathies (i.e. 7.2%) diagnosed thanks to a film of the urinary apparatus taken during angiocardiography. These uropathies were encountered mainly during ventricular septal defects, pulmonary stenosis and Fallot's tetralogy. The diagnostic value of the film during angiocardiography is great as it revealed 22 out of 49 uropathies (i.e. 44.9%) clinically silent until then."}
{"id": "PMID:210517", "title": "[Epidemiologic study of 850 children with burns requiring hospitalization].", "content": "This study concerns 850 cases of burns in children. It showed the predominance of burns in boys between the ages of one and 3 years. Most domestic accidents (96.5%) were due to boiling water (55.9%), the second cause was burns due to a flame (11.7%). Most accidents arrived at meal times. The area of burnt skin was as follows:--in 222 cases, less than 5%;--in 365 cases, between 5 and ten percent;--in 152 cases, bwtween 10 and 25%;--in 111 cases, more than 25%.", "contents": "[Epidemiologic study of 850 children with burns requiring hospitalization]. This study concerns 850 cases of burns in children. It showed the predominance of burns in boys between the ages of one and 3 years. Most domestic accidents (96.5%) were due to boiling water (55.9%), the second cause was burns due to a flame (11.7%). Most accidents arrived at meal times. The area of burnt skin was as follows:--in 222 cases, less than 5%;--in 365 cases, between 5 and ten percent;--in 152 cases, bwtween 10 and 25%;--in 111 cases, more than 25%."}
{"id": "PMID:210518", "title": "[Non-addictive properties of tiapride (1347)].", "content": "Possible addiction to tiapride was sought in a 10 kg Beagle dog and an ordinary 12 kg dog using the substitution method suggested by J.J. Deglarez. Tiapride at a dose of 30 mg/kg was not able to interrupt the state of hyperexcitability triggered off by sudden morphine withdrawal. On may consider that tiapride is completely lacking in addictive properties.", "contents": "[Non-addictive properties of tiapride (1347)]. Possible addiction to tiapride was sought in a 10 kg Beagle dog and an ordinary 12 kg dog using the substitution method suggested by J.J. Deglarez. Tiapride at a dose of 30 mg/kg was not able to interrupt the state of hyperexcitability triggered off by sudden morphine withdrawal. On may consider that tiapride is completely lacking in addictive properties."}
{"id": "PMID:210520", "title": "[Nervous and digestive manifestations in chronic alcoholism. Their treatment by tiapride].", "content": "Triapride has proved to be effective for the treatmentof neurological and digestive disorders associated with chronic alcoholism. The clinical and physiopathological aspects of this disease are discussed briefly. Tiapride has a significantly effective action on tremor and muscular pains in moderate cases of alcoholism.--It corrects changes in hebanour and mood.--It improves appetite stimulating the desir for food and reducing the overall functional symptomatology. Tiapride is well-tolerated and vigilance is not modified.", "contents": "[Nervous and digestive manifestations in chronic alcoholism. Their treatment by tiapride]. Triapride has proved to be effective for the treatmentof neurological and digestive disorders associated with chronic alcoholism. The clinical and physiopathological aspects of this disease are discussed briefly. Tiapride has a significantly effective action on tremor and muscular pains in moderate cases of alcoholism.--It corrects changes in hebanour and mood.--It improves appetite stimulating the desir for food and reducing the overall functional symptomatology. Tiapride is well-tolerated and vigilance is not modified."}
{"id": "PMID:210523", "title": "Bronchial adenoma--benign or malignant?", "content": "Bronchial adenomas grow slowly and are potentially malignant. Of the 45 cases reviewed, 36 were carcinoids, six were adenocystic carcinomas, two were mixed tumors, and one was mucoepidermoid carcinoma. The carcinoid group is subdivided into histologically typical 27(75%), atypical 9 (25%), and metastasizing 9 (25%) adenomas. There were 32 lobectomies, seven pneumonectomies, one sleeve resection, and two tracheal resections for adenocystic carcinoma. Ten-year survival rate was 88% for typical carcinoids, 66% for atypical carcinoids, and 44% for metastasizing carcinoids. In the cylindroma group, one patient was lost to follow-up, one died postoperatively, and one developed recurrence of the tumor eight years later. The only patient with mucoepidermoid carcinoma is alive without evidence of recurrence nine years after operation.", "contents": "Bronchial adenoma--benign or malignant? Bronchial adenomas grow slowly and are potentially malignant. Of the 45 cases reviewed, 36 were carcinoids, six were adenocystic carcinomas, two were mixed tumors, and one was mucoepidermoid carcinoma. The carcinoid group is subdivided into histologically typical 27(75%), atypical 9 (25%), and metastasizing 9 (25%) adenomas. There were 32 lobectomies, seven pneumonectomies, one sleeve resection, and two tracheal resections for adenocystic carcinoma. Ten-year survival rate was 88% for typical carcinoids, 66% for atypical carcinoids, and 44% for metastasizing carcinoids. In the cylindroma group, one patient was lost to follow-up, one died postoperatively, and one developed recurrence of the tumor eight years later. The only patient with mucoepidermoid carcinoma is alive without evidence of recurrence nine years after operation."}
{"id": "PMID:210526", "title": "Pleiotropic drug resistance in cystic fibrosis fibroblasts: increased resistance to cyclic AMP.", "content": "In previous studies, cystic fibrosis (CF) fibroblasts were demonstrated to be resistant to the cytotoxic effects of ouabain, dexamethasone, and the sex hormones, dihydrotestosterone, 17beta-estradiol, and progesterone. We now show that CF fibroblasts also exhibit greatly increased resistance to the cytotoxic effects of exogenous dibutyryl cyclic AMP (cAMP), as well as to isoproterenol and theophylline, drugs which are known to increase endogenous levels of cAMP. CF cells were also shown to have normal amounts of (3H)cAMP binding to protein kinase as well as normal amounts of cAMP-stimulated protein kinase activity. Phosphodiesterase in CF cells was also found to be stimulated by cAMP to the same degree as in normal cells. These findings suggest that there is no detectable protein kinase deficiency in CF cells. cf cells thus appear to be unlike some cAMP-resistant mutants described by others which are defective in protein kinase activity and cAMP regulation of phosphodiesterase levels. The cross-resistance of CF fibroblasts to ouabain, steroid hormones, and cAMP may provide a unique opportunity to study the biochemical events involved in the metabolism of these drugs as well as the basic biochemical defect in a common human genetic disease.", "contents": "Pleiotropic drug resistance in cystic fibrosis fibroblasts: increased resistance to cyclic AMP. In previous studies, cystic fibrosis (CF) fibroblasts were demonstrated to be resistant to the cytotoxic effects of ouabain, dexamethasone, and the sex hormones, dihydrotestosterone, 17beta-estradiol, and progesterone. We now show that CF fibroblasts also exhibit greatly increased resistance to the cytotoxic effects of exogenous dibutyryl cyclic AMP (cAMP), as well as to isoproterenol and theophylline, drugs which are known to increase endogenous levels of cAMP. CF cells were also shown to have normal amounts of (3H)cAMP binding to protein kinase as well as normal amounts of cAMP-stimulated protein kinase activity. Phosphodiesterase in CF cells was also found to be stimulated by cAMP to the same degree as in normal cells. These findings suggest that there is no detectable protein kinase deficiency in CF cells. cf cells thus appear to be unlike some cAMP-resistant mutants described by others which are defective in protein kinase activity and cAMP regulation of phosphodiesterase levels. The cross-resistance of CF fibroblasts to ouabain, steroid hormones, and cAMP may provide a unique opportunity to study the biochemical events involved in the metabolism of these drugs as well as the basic biochemical defect in a common human genetic disease."}
{"id": "PMID:210528", "title": "Pregnancy and breast cancer.", "content": "Breast cancer in association with pregnancy and lactation is rare, but presents a therapeutic problem of considerable magnitude. The outlook for such patients is less favorable than that of nonpregnant, nonlactating women, probably because the stage of the disease is more advanced when it is discovered. The most significant factor in the poorer prognosis is physician delay in diagnosis and therapy. When mastectomy is carried out early in pregnancy, the operation can be as effective as in nonpregnant women of the same age groups. It is emphasized that when pregnancy and breast cancer are found concurrently, prompt therapy for the cancer should be undertaken. Interruption of pregnancy in nondisseminated breast cancer is of little value. If pregnancy is near term when the diagnosis of disseminated breast cancer is made, the desire of the husband and wife for a child should be considered. A modest delay in therapy to allow for delivery probably has no deleterious effect. Castration should be withheld and used only for the patient with metastatic disease. There may be a place for prophylactic castration in the treatment of disseminated disease, but its role is yet to be clearly defined. Subsequent pregnancies in a patient with axillary spread at the time of mastectomy are contraindicated, because of the high rate of treatment failure and decreased rate of survival. In patients desiring future pregnancies following mastectomy, a period of observation of at least 2 years seems wise. At the end of that period, if clinical evaluation, laboratory values, roentgenographic studies, and isotopic bone scanning are negative for disseminated disease, subsequent pregnancies seem safe. Prompt evaluation of any breast mass found during pregnancy and lactation should be carried out by needle or operative biopsies under local anesthesia. Although the prognosis of the pregnant or lactating woman with breast cancer is generally favorable, numerous long-term survivals are encountered in those women who undergo prompt mastectomy early in pregnancy. The former pessimistic outlook for such patients seems unjustified. With modern methods of diagnosis and treatment, therapy can be effective and successful.", "contents": "Pregnancy and breast cancer. Breast cancer in association with pregnancy and lactation is rare, but presents a therapeutic problem of considerable magnitude. The outlook for such patients is less favorable than that of nonpregnant, nonlactating women, probably because the stage of the disease is more advanced when it is discovered. The most significant factor in the poorer prognosis is physician delay in diagnosis and therapy. When mastectomy is carried out early in pregnancy, the operation can be as effective as in nonpregnant women of the same age groups. It is emphasized that when pregnancy and breast cancer are found concurrently, prompt therapy for the cancer should be undertaken. Interruption of pregnancy in nondisseminated breast cancer is of little value. If pregnancy is near term when the diagnosis of disseminated breast cancer is made, the desire of the husband and wife for a child should be considered. A modest delay in therapy to allow for delivery probably has no deleterious effect. Castration should be withheld and used only for the patient with metastatic disease. There may be a place for prophylactic castration in the treatment of disseminated disease, but its role is yet to be clearly defined. Subsequent pregnancies in a patient with axillary spread at the time of mastectomy are contraindicated, because of the high rate of treatment failure and decreased rate of survival. In patients desiring future pregnancies following mastectomy, a period of observation of at least 2 years seems wise. At the end of that period, if clinical evaluation, laboratory values, roentgenographic studies, and isotopic bone scanning are negative for disseminated disease, subsequent pregnancies seem safe. Prompt evaluation of any breast mass found during pregnancy and lactation should be carried out by needle or operative biopsies under local anesthesia. Although the prognosis of the pregnant or lactating woman with breast cancer is generally favorable, numerous long-term survivals are encountered in those women who undergo prompt mastectomy early in pregnancy. The former pessimistic outlook for such patients seems unjustified. With modern methods of diagnosis and treatment, therapy can be effective and successful."}
{"id": "PMID:210529", "title": "The effect of splanchnic viscera removal upon canine liver regeneration.", "content": "The influence of portal blood factors on canine liver regeneration was studied with graded nonhepatic splanchnic evisceration, coupled with 44 and 72 per cent hepatectomies. In one type of experiment, the pancreas was retained while the rest of the intra-abdominal gastrointestinal tract was removed. In a second variety, total pancreatectomy was performed with preservation of the intra-abdominal organs. In a third kind of experiment, total nonhepatic splanchnic evisceration was performed. Liver regeneration after hepatectomy was decreased by all three kinds of viscera removed as judged by deoxyribonucleic acid synthesis, autoradiography and mitotic index. Pancreatectomy and nonpancreatic splanchnic evisceration caused almost equal decreases in the regenerative response. Total nonhepatic splanchnic evisceration essentially halted regeneration during the first three postoperative days and intraportal infusions of insulin or glucagon, or both together, did not reverse this effect. The decrease in liver membrane bound adenyl cyclase activity and biphasic change in liver cyclic 3', 5' -adenosine monophosphate concentrations normally seen after partial hepatectomy were disrupted after the various eviscerations. Adenyl cyclase activity and cyclic 3', 5' -adenosine monophosphate concentrations tended to be higher than normal in the eviscerated dogs. These observations provide more support for our previously proposed hypothesis that control of liver regeneration is by multiple factors. Pancreatic hormones are important modifiers of this response but, by no means, exercise exclusive control. Other substances of gastrointestinal origin, presumably including hormones and nutrient supply apparently play important specific roles. The volume of portal flow is a secondary and nonspecific, but possibly significant, factor.", "contents": "The effect of splanchnic viscera removal upon canine liver regeneration. The influence of portal blood factors on canine liver regeneration was studied with graded nonhepatic splanchnic evisceration, coupled with 44 and 72 per cent hepatectomies. In one type of experiment, the pancreas was retained while the rest of the intra-abdominal gastrointestinal tract was removed. In a second variety, total pancreatectomy was performed with preservation of the intra-abdominal organs. In a third kind of experiment, total nonhepatic splanchnic evisceration was performed. Liver regeneration after hepatectomy was decreased by all three kinds of viscera removed as judged by deoxyribonucleic acid synthesis, autoradiography and mitotic index. Pancreatectomy and nonpancreatic splanchnic evisceration caused almost equal decreases in the regenerative response. Total nonhepatic splanchnic evisceration essentially halted regeneration during the first three postoperative days and intraportal infusions of insulin or glucagon, or both together, did not reverse this effect. The decrease in liver membrane bound adenyl cyclase activity and biphasic change in liver cyclic 3', 5' -adenosine monophosphate concentrations normally seen after partial hepatectomy were disrupted after the various eviscerations. Adenyl cyclase activity and cyclic 3', 5' -adenosine monophosphate concentrations tended to be higher than normal in the eviscerated dogs. These observations provide more support for our previously proposed hypothesis that control of liver regeneration is by multiple factors. Pancreatic hormones are important modifiers of this response but, by no means, exercise exclusive control. Other substances of gastrointestinal origin, presumably including hormones and nutrient supply apparently play important specific roles. The volume of portal flow is a secondary and nonspecific, but possibly significant, factor."}
{"id": "PMID:210530", "title": "Interventions in atherosclerosis: a review for surgeons.", "content": "For the surgeon, atherosclerosis is defined by a variety of aneurysmal, occlusive, or ulcerated lesions in major arteries. These end-stage lesions often require operative treatment. However, just as advanced atherosclerosis presents complex clinical phenomena, so its earlier stages display many underlying mechanisms promoting lesions. To arrest or control atherosclerosis, the disease must be approached with knowledge about diverse biological processes. These include ceullar and systemic aspects of lipoprotein metabolism, reactions and metabolism of endothelium and smooth muscle cells of the arterial wall, and interaction of platelets with the arterial intima. The chronic nature of this process is such that surgeons are involved intimately with overall management as well as with surgical procedures. We will review underlying biological processes of atherosclerosis as related to interventions in patients with clinically apparent disease.", "contents": "Interventions in atherosclerosis: a review for surgeons. For the surgeon, atherosclerosis is defined by a variety of aneurysmal, occlusive, or ulcerated lesions in major arteries. These end-stage lesions often require operative treatment. However, just as advanced atherosclerosis presents complex clinical phenomena, so its earlier stages display many underlying mechanisms promoting lesions. To arrest or control atherosclerosis, the disease must be approached with knowledge about diverse biological processes. These include ceullar and systemic aspects of lipoprotein metabolism, reactions and metabolism of endothelium and smooth muscle cells of the arterial wall, and interaction of platelets with the arterial intima. The chronic nature of this process is such that surgeons are involved intimately with overall management as well as with surgical procedures. We will review underlying biological processes of atherosclerosis as related to interventions in patients with clinically apparent disease."}
{"id": "PMID:210531", "title": "Intrathoracic neural tumours.", "content": "The experience of one regional thoracic surgical unit in managing intrathoracic neural tumours over a 25-year period is presented. Neural tumour was diagnosed in 55 patients, of whom 41 were asymptomatic. In 11 patients complete resection was not achieved--the reasons for this and its effect on the outcome of the patient are discussed. There were 52 posterior mediastinal and three lateral chest wall tumours. The pathological distribution was as follows--benign nerve sheath tumours (neurofibroma, neurilemoma) 39, ganglioneuroma 13, and neuroblastoma 3. One neurofibroma recurred as a neurosarcoma six years after its apparently complete resection and was removed by an extensive resection at reoperation. One neuroblastoma recurred within the spinal canal four years after incomplete excision at thoracotomy--this patient died subsequently of widespread metastatic neuroblastoma. No other tumour is known to have recurred.", "contents": "Intrathoracic neural tumours. The experience of one regional thoracic surgical unit in managing intrathoracic neural tumours over a 25-year period is presented. Neural tumour was diagnosed in 55 patients, of whom 41 were asymptomatic. In 11 patients complete resection was not achieved--the reasons for this and its effect on the outcome of the patient are discussed. There were 52 posterior mediastinal and three lateral chest wall tumours. The pathological distribution was as follows--benign nerve sheath tumours (neurofibroma, neurilemoma) 39, ganglioneuroma 13, and neuroblastoma 3. One neurofibroma recurred as a neurosarcoma six years after its apparently complete resection and was removed by an extensive resection at reoperation. One neuroblastoma recurred within the spinal canal four years after incomplete excision at thoracotomy--this patient died subsequently of widespread metastatic neuroblastoma. No other tumour is known to have recurred."}
{"id": "PMID:210545", "title": "Cellular immunity to cytomegalovirus in a patient following bone marrow transplantation.", "content": "Cell-mediated immunity to cytomegalovirus (CMV) was studied in a bone marrow transplant patient with evidence of active CMV infection. The lymphocytes from this patient were found to specifically recognize and respond in vitro by transformation to CMV-infected Wistar-38 fibroblasts and by production of macrophage migration inhibition factor to CMV antigen. In addition, plasma and spinal fluid from the patient were found to contain blocking factor that specifically inhibited the lymphocyte response in the above assays. Biochemical, biophysical, and immunological studies indicate that the blocking factor may be an antigen-antibody complex.", "contents": "Cellular immunity to cytomegalovirus in a patient following bone marrow transplantation. Cell-mediated immunity to cytomegalovirus (CMV) was studied in a bone marrow transplant patient with evidence of active CMV infection. The lymphocytes from this patient were found to specifically recognize and respond in vitro by transformation to CMV-infected Wistar-38 fibroblasts and by production of macrophage migration inhibition factor to CMV antigen. In addition, plasma and spinal fluid from the patient were found to contain blocking factor that specifically inhibited the lymphocyte response in the above assays. Biochemical, biophysical, and immunological studies indicate that the blocking factor may be an antigen-antibody complex."}
{"id": "PMID:210547", "title": "[Poly (ADP-ribose), ADP-ribosylation of proteins and regulation of cell activity].", "content": "The nature of a before unknown biological activity of NAD as a substrate in protein modification reaction is considered. Upon enzymatic digestion of NAD its adenosinediphosphate ribose (ADPR) part is transferred to acceptor proteins. ADPR in its mono- or polymeric form is covalently linked to proteins at the expense of NAD's high energy bound. Negatively charged ADPR, in association with a protein, is able to alter the charge, conformation and biological activity of the latter. The reaction is important in structural rearrangements of chromatin, in the synthesis and repair of DNA, in cell growth and differentiation and in the mechanisms of actions of actions of bacterial toxins.", "contents": "[Poly (ADP-ribose), ADP-ribosylation of proteins and regulation of cell activity]. The nature of a before unknown biological activity of NAD as a substrate in protein modification reaction is considered. Upon enzymatic digestion of NAD its adenosinediphosphate ribose (ADPR) part is transferred to acceptor proteins. ADPR in its mono- or polymeric form is covalently linked to proteins at the expense of NAD's high energy bound. Negatively charged ADPR, in association with a protein, is able to alter the charge, conformation and biological activity of the latter. The reaction is important in structural rearrangements of chromatin, in the synthesis and repair of DNA, in cell growth and differentiation and in the mechanisms of actions of actions of bacterial toxins."}
{"id": "PMID:210551", "title": "[Autonomous hyperparathyroidism--diagnostic values of laboratory parameters (author's transl)].", "content": "The diagnostic parameters of HPT in 22 patients with recurrent urinary stone disease and high levels of PTH were investigated with particular reference of their practical value and reliability. Among the diagnostic parameters PTH and ionized calcium in serum and calcium/creatinine ratio, TRP p. c. and c-AMP in urin after overnight fasting have the best reliability.", "contents": "[Autonomous hyperparathyroidism--diagnostic values of laboratory parameters (author's transl)]. The diagnostic parameters of HPT in 22 patients with recurrent urinary stone disease and high levels of PTH were investigated with particular reference of their practical value and reliability. Among the diagnostic parameters PTH and ionized calcium in serum and calcium/creatinine ratio, TRP p. c. and c-AMP in urin after overnight fasting have the best reliability."}
{"id": "PMID:210549", "title": "[Disc-electrophoresis of proteins and infrared spectroscopy of Rous sarcoma tissue].", "content": "A study of sarcoma was carried out in the process of its development in the chicken muscular tissue. Simplification of the protein composition and IR-spectra of the tumour are established which is manifested in an increase in the content of albuminous proteins and in a decrease in some globulin fractions, in disappearance of two IR spectrum bands as well as in changes in relative optical density of the bands at 1560 and 1380 cm-1.", "contents": "[Disc-electrophoresis of proteins and infrared spectroscopy of Rous sarcoma tissue]. A study of sarcoma was carried out in the process of its development in the chicken muscular tissue. Simplification of the protein composition and IR-spectra of the tumour are established which is manifested in an increase in the content of albuminous proteins and in a decrease in some globulin fractions, in disappearance of two IR spectrum bands as well as in changes in relative optical density of the bands at 1560 and 1380 cm-1."}
{"id": "PMID:210548", "title": "[On 14C-nicotinate penetration into cellular and subcellular structures of animals following adrenalectomy and hormone administration].", "content": "The experiments on the Wistar line rats and mongrel dogs showed that gravitational overloading, surgical and chemical adrenalectomy, injections of certain hormones and actinomycin D affect essentially the permeability of blood cells and liver mitochondria to 14C nicotinic acid. An assumption is advanced that the transport of 14C nicotinic acid to biological structures occurs with participation of complex mechanisms, the function of which is regulated by hormones and is coupled with the processes of protein synthesis.", "contents": "[On 14C-nicotinate penetration into cellular and subcellular structures of animals following adrenalectomy and hormone administration]. The experiments on the Wistar line rats and mongrel dogs showed that gravitational overloading, surgical and chemical adrenalectomy, injections of certain hormones and actinomycin D affect essentially the permeability of blood cells and liver mitochondria to 14C nicotinic acid. An assumption is advanced that the transport of 14C nicotinic acid to biological structures occurs with participation of complex mechanisms, the function of which is regulated by hormones and is coupled with the processes of protein synthesis."}
{"id": "PMID:210556", "title": "Prevention of avian lymphoid leukosis by induction of bursal atrophy with infectious bursal disease viruses.", "content": "Five groups of genetically susceptible chickens were inoculated at hatching with lymphoid leukosis virus; four of these were given infectious bursal viruses of varying virulence at 14 days of age and one group was not inoculated (control). All chickens in the control group developed evidence of lymphoid leukosis by 180 days. Two groups given relatively virulent bursal disease viruses, which destroyed bursal lymphoid cells, did not develop lymphoid leukosis. Treatment with avirulent vaccines had no visible effect on bursal morphology and did not significantly alter the incidence of lymphoid leukosis in two other groups, although the time of development was delayed. Results of our study show that viral-induced destruction of the bursa of Fabricius eliminates the development of lymphoid leukosis but that infection without bursal destruction has little effect on lymphoid leukosis.", "contents": "Prevention of avian lymphoid leukosis by induction of bursal atrophy with infectious bursal disease viruses. Five groups of genetically susceptible chickens were inoculated at hatching with lymphoid leukosis virus; four of these were given infectious bursal viruses of varying virulence at 14 days of age and one group was not inoculated (control). All chickens in the control group developed evidence of lymphoid leukosis by 180 days. Two groups given relatively virulent bursal disease viruses, which destroyed bursal lymphoid cells, did not develop lymphoid leukosis. Treatment with avirulent vaccines had no visible effect on bursal morphology and did not significantly alter the incidence of lymphoid leukosis in two other groups, although the time of development was delayed. Results of our study show that viral-induced destruction of the bursa of Fabricius eliminates the development of lymphoid leukosis but that infection without bursal destruction has little effect on lymphoid leukosis."}
{"id": "PMID:210557", "title": "Studies on cross protection induced in calves by rotaviruses of calves, children and foals.", "content": "Inoculation at birth with a live attenuated strain of a bovine rotavirus isolated in the USA (scourvax-reo) induced protection in five gnotobiotic calves seven to 21 days later against a UK isolate of pathogenic bovine rotavirus. However, no protection was induced in three calves challenged three to five days after vaccination. There was a close antigenic relationship demonstrated between the two bovine rotavirus isolates. In contrast only one of three gnotobiotic calves inoculated with foal rotavirus, and one of three with human rotavirus, were protected against bovine rotavirus challenge. Protection in these two calves correlated with high heterologous immunofluorescent antibody titre (320 or greater), although the neutralising antibody titres was less than 20.", "contents": "Studies on cross protection induced in calves by rotaviruses of calves, children and foals. Inoculation at birth with a live attenuated strain of a bovine rotavirus isolated in the USA (scourvax-reo) induced protection in five gnotobiotic calves seven to 21 days later against a UK isolate of pathogenic bovine rotavirus. However, no protection was induced in three calves challenged three to five days after vaccination. There was a close antigenic relationship demonstrated between the two bovine rotavirus isolates. In contrast only one of three gnotobiotic calves inoculated with foal rotavirus, and one of three with human rotavirus, were protected against bovine rotavirus challenge. Protection in these two calves correlated with high heterologous immunofluorescent antibody titre (320 or greater), although the neutralising antibody titres was less than 20."}
{"id": "PMID:210561", "title": "[Comparative studies of the virulence of some Aujeszky's disease viral strains].", "content": "Clinical, virological, morphological, and immunofluorescence investigations were carried out on 22 pigs experimentally infected with two strains--a virulent one (V) of a 10(-3) titer, and a slightly virulent one (K) of a 10(-7) titer--of the virus of Aujeszky's disease as well as on contact pigs. Results revealed variations in the clinical and morphological manifestation of the disease in the individual groups. They were shown to be due to the strains of the virus that varied in virulence and tissue tropism. In the strain B-infected animals there were clinical symptoms characteristic of the disease, and the morphological changes in the central nervous system were of the nonsuppurative encephalitis type. The pigs infected with the K strain of the virus showed no clinical symptoms, while the contact animals manifested only respiratory troubles as well as interstitial pneumonia. It was demonstrated that the strains of slight virulence had weak nervotropic and pronounced pneumotropic characters. Complex virologic, morphologic and immunofluorescence investigations can be used for the diagnosis of the atypical forms of Aujeszky's disease and for the differentiation of the virulent from the slightly virulent strains of the virus.", "contents": "[Comparative studies of the virulence of some Aujeszky's disease viral strains]. Clinical, virological, morphological, and immunofluorescence investigations were carried out on 22 pigs experimentally infected with two strains--a virulent one (V) of a 10(-3) titer, and a slightly virulent one (K) of a 10(-7) titer--of the virus of Aujeszky's disease as well as on contact pigs. Results revealed variations in the clinical and morphological manifestation of the disease in the individual groups. They were shown to be due to the strains of the virus that varied in virulence and tissue tropism. In the strain B-infected animals there were clinical symptoms characteristic of the disease, and the morphological changes in the central nervous system were of the nonsuppurative encephalitis type. The pigs infected with the K strain of the virus showed no clinical symptoms, while the contact animals manifested only respiratory troubles as well as interstitial pneumonia. It was demonstrated that the strains of slight virulence had weak nervotropic and pronounced pneumotropic characters. Complex virologic, morphologic and immunofluorescence investigations can be used for the diagnosis of the atypical forms of Aujeszky's disease and for the differentiation of the virulent from the slightly virulent strains of the virus."}
{"id": "PMID:210562", "title": "[Attempts to demonstrate and identify avian adenoviruses by an immunofluorescence method].", "content": "A specific conjugate of a hyperimmune serum, obtained from rabbits with the use of the reference Phelps-CELO strain, was employed in a direct immunofluorescence method to investigate more than 320 lamelles with cell cultures infected with 4 field CELO virus strains and the reference Phelps-CELO strain. It is stated this method is specific and prompt for the early diagnosis and identification of adenoviruses (CELO viruses).", "contents": "[Attempts to demonstrate and identify avian adenoviruses by an immunofluorescence method]. A specific conjugate of a hyperimmune serum, obtained from rabbits with the use of the reference Phelps-CELO strain, was employed in a direct immunofluorescence method to investigate more than 320 lamelles with cell cultures infected with 4 field CELO virus strains and the reference Phelps-CELO strain. It is stated this method is specific and prompt for the early diagnosis and identification of adenoviruses (CELO viruses)."}
{"id": "PMID:210563", "title": "[Action of actidion on the replication of the transmissible gastroenteritis virus].", "content": "Explored was the possibility of inhibiting the replication of the virus of the transmissive gastroenteritis by means of actidione. It was found that in certain concentrations the antibiotic completely inhibited the replication of this virus. In individual strains the process of replication was not influenced by the various concentrations applied. It was demonstrated that when the antibiotic was added to the infected cell cultures during individual phases its varying concentrations influenced the virus replication. When actidione was added to the cells at the time of virus adsorption it did not inhibit the synthesis of the virus. Similar were the results when the cells were cultivated 24 hours with specified concentrations of actidione prior to their infection with the virus.", "contents": "[Action of actidion on the replication of the transmissible gastroenteritis virus]. Explored was the possibility of inhibiting the replication of the virus of the transmissive gastroenteritis by means of actidione. It was found that in certain concentrations the antibiotic completely inhibited the replication of this virus. In individual strains the process of replication was not influenced by the various concentrations applied. It was demonstrated that when the antibiotic was added to the infected cell cultures during individual phases its varying concentrations influenced the virus replication. When actidione was added to the cells at the time of virus adsorption it did not inhibit the synthesis of the virus. Similar were the results when the cells were cultivated 24 hours with specified concentrations of actidione prior to their infection with the virus."}
{"id": "PMID:210585", "title": "[Effect of denervation on carbohydrate metabolism in the liver].", "content": "Activities of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase and content of glycogen in liver as well as content of sugar in blood were studied after denervation of dog liver tissue. Activities of these enzymes were increased and content of glycogen in hepatocytes was decreased within 1-2 weeks after the denervation. Within a month the enzymatic activities and content of glycogen in liver tissue approached the control levels; these patterns were similar to control ones within the subsequent periods of examination (3-months--1 year). Content of sugar in blood was the same within all the periods of study (3 days--3 months).", "contents": "[Effect of denervation on carbohydrate metabolism in the liver]. Activities of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase and content of glycogen in liver as well as content of sugar in blood were studied after denervation of dog liver tissue. Activities of these enzymes were increased and content of glycogen in hepatocytes was decreased within 1-2 weeks after the denervation. Within a month the enzymatic activities and content of glycogen in liver tissue approached the control levels; these patterns were similar to control ones within the subsequent periods of examination (3-months--1 year). Content of sugar in blood was the same within all the periods of study (3 days--3 months)."}
{"id": "PMID:210586", "title": "[Lipoprotein lipase fractionation of very low density serum lipoproteins from healthy subjects and persons afflicted with atherosclerosis].", "content": "In vitro experiments showed that blood sera of the patients with atherosclerosis contained rather often the fraction of very low density lipoproteins (VLDL) with sf 100-400 S, which were cleaved by the lipoprotein lipase at the decreased rate as compared with that of normal people. The decrease in cleavage of the VLDL fraction was usually observed in patients with the increased concentration of the lipoprotein fraction in blood sera. These data suggest that separate constituents occurring in the VLDL fraction (sf 100-400 S) may be nonuniformly increased in hyperlipoproteinemia.", "contents": "[Lipoprotein lipase fractionation of very low density serum lipoproteins from healthy subjects and persons afflicted with atherosclerosis]. In vitro experiments showed that blood sera of the patients with atherosclerosis contained rather often the fraction of very low density lipoproteins (VLDL) with sf 100-400 S, which were cleaved by the lipoprotein lipase at the decreased rate as compared with that of normal people. The decrease in cleavage of the VLDL fraction was usually observed in patients with the increased concentration of the lipoprotein fraction in blood sera. These data suggest that separate constituents occurring in the VLDL fraction (sf 100-400 S) may be nonuniformly increased in hyperlipoproteinemia."}
{"id": "PMID:210587", "title": "[Reaction between cGMP and cAMP in their effect on muscle carbohydrate metabolism].", "content": "cGMP (10(-4)-10(-7) M) did not affect the activity of phosphorylase and glycogen synthetase from chicken sceletal muscles; but the cGMP prevented completely an effect of cAMP on the enzymes. This blocking effect was specific for cGMP (GMP did not exhibit the effect) and for cAMP (influence of calcium on the enzyme was not eliminated by cAMP). Possible mechanisms of the cGMP effects studied are considered: 1) stimulation of cAMP hydrolysis, 2) antagonism at the level of proteinkinase system. cGMP (10(-4)-10(-7) M) did not stimulate the phosphodiesterase activity at millimolar concentration of its substrate--cAMP.", "contents": "[Reaction between cGMP and cAMP in their effect on muscle carbohydrate metabolism]. cGMP (10(-4)-10(-7) M) did not affect the activity of phosphorylase and glycogen synthetase from chicken sceletal muscles; but the cGMP prevented completely an effect of cAMP on the enzymes. This blocking effect was specific for cGMP (GMP did not exhibit the effect) and for cAMP (influence of calcium on the enzyme was not eliminated by cAMP). Possible mechanisms of the cGMP effects studied are considered: 1) stimulation of cAMP hydrolysis, 2) antagonism at the level of proteinkinase system. cGMP (10(-4)-10(-7) M) did not stimulate the phosphodiesterase activity at millimolar concentration of its substrate--cAMP."}
{"id": "PMID:210588", "title": "[Biochemical features of the liver of high and low cancer mouse strains and primary spontaneous hepatomas].", "content": "Sex differences in development of spontaneous liver tumors were studied in mice of CBA strain. Content of mitochondrial proteins, activities of cytochrome oxidase, glucokinase, hexokinase as well as subcellular distribution of hexokinase were also studied in primary hepatomas and in normal liver tissue of the mice of CBA and C3HA strains. Liver tumors occurred in males of CBA strain 7-fold more frequently than in females. Activities of hexokinase, glucokinase, cytochrome oxidase and content of mitochondrial proteins were distinctly alterep both in primary spontaneous hepatomas and in transplantable strains. But, contrary to the transplantable tumors, in spontaneous hepatomas hexokinase, associated with mitochondria, was not found. Decrease in activities of glucokinase and cytochrome oxidase was observed at the early stages of development of CBA strain in males as compared with females of CBA and males of C3HA strains, i.e. distinct decrease in several functional patterns of liver tissue was observed. Subcutaneous administration of orthoamine azotoluene into mice of the C3HA strain caused alteration in activity of these enzymes from liver tissue, which was typical for hepatomas, already at the early steps of development.", "contents": "[Biochemical features of the liver of high and low cancer mouse strains and primary spontaneous hepatomas]. Sex differences in development of spontaneous liver tumors were studied in mice of CBA strain. Content of mitochondrial proteins, activities of cytochrome oxidase, glucokinase, hexokinase as well as subcellular distribution of hexokinase were also studied in primary hepatomas and in normal liver tissue of the mice of CBA and C3HA strains. Liver tumors occurred in males of CBA strain 7-fold more frequently than in females. Activities of hexokinase, glucokinase, cytochrome oxidase and content of mitochondrial proteins were distinctly alterep both in primary spontaneous hepatomas and in transplantable strains. But, contrary to the transplantable tumors, in spontaneous hepatomas hexokinase, associated with mitochondria, was not found. Decrease in activities of glucokinase and cytochrome oxidase was observed at the early stages of development of CBA strain in males as compared with females of CBA and males of C3HA strains, i.e. distinct decrease in several functional patterns of liver tissue was observed. Subcutaneous administration of orthoamine azotoluene into mice of the C3HA strain caused alteration in activity of these enzymes from liver tissue, which was typical for hepatomas, already at the early steps of development."}
{"id": "PMID:210590", "title": "[Serum lipoproteins in the generalized form of type III glycogenosis].", "content": "Distinct accumulation of glycogen, anomalous in structure, and absence of amylo-1,6-glucosidase activity were observed in studies of material obtained by biopsy from liver and muscle tissues of a patient with generalized form of glycogenosis type III. Anamalous glycogen (limitdextrin) was also found in erythrocytes. Concentration of lipoproteins, especially of low density lipoproteins 12.20 S and 0-12 S, was increased in blood serum. Spectrum of lipoproteins acquired a tendency to normalization simultaneously with clinical improvement after intravenous administration of glucose and treatment with cholesterolamine per os.", "contents": "[Serum lipoproteins in the generalized form of type III glycogenosis]. Distinct accumulation of glycogen, anomalous in structure, and absence of amylo-1,6-glucosidase activity were observed in studies of material obtained by biopsy from liver and muscle tissues of a patient with generalized form of glycogenosis type III. Anamalous glycogen (limitdextrin) was also found in erythrocytes. Concentration of lipoproteins, especially of low density lipoproteins 12.20 S and 0-12 S, was increased in blood serum. Spectrum of lipoproteins acquired a tendency to normalization simultaneously with clinical improvement after intravenous administration of glucose and treatment with cholesterolamine per os."}
{"id": "PMID:210591", "title": "[Spin label study of plasma lipoproteins].", "content": "Lipoprotein structure was studied by means of EPR-spectroscopy of spin probes--iminoxyl derivatives of stearic acid and of androstane--in blood plasma of 40-59 years old men. The mode of wrapping of external monolayer of lipoprotein particles, the type of their intermolecular interactions were similar to corresponding characteristics of bilayer in biological and model membranes. Correlation was observed between concentration of separate lipoproteins in blood plasma and the structural parameters of the probe distribution in hydrophobic and polar regions of the lipoprotein preparations. The phenomena observed might be related to capacity of the high density lipoproteins to accept cholesterol from cell membranes with transfer of cholesterol into liver tissue, where it is subsequently metabolized, as well as to the property of the very low density lipoproteins to transfer cholesterol into tissues, particularly, into vascular walls.", "contents": "[Spin label study of plasma lipoproteins]. Lipoprotein structure was studied by means of EPR-spectroscopy of spin probes--iminoxyl derivatives of stearic acid and of androstane--in blood plasma of 40-59 years old men. The mode of wrapping of external monolayer of lipoprotein particles, the type of their intermolecular interactions were similar to corresponding characteristics of bilayer in biological and model membranes. Correlation was observed between concentration of separate lipoproteins in blood plasma and the structural parameters of the probe distribution in hydrophobic and polar regions of the lipoprotein preparations. The phenomena observed might be related to capacity of the high density lipoproteins to accept cholesterol from cell membranes with transfer of cholesterol into liver tissue, where it is subsequently metabolized, as well as to the property of the very low density lipoproteins to transfer cholesterol into tissues, particularly, into vascular walls."}
{"id": "PMID:210589", "title": "[Detection of autoimmune lipoprotein--antibody complex in human plasma and aortic wall].", "content": "An immune complex of lipoprotein-antibody was found in human blood plasma and in tissue liquid of aorta, impaired by atherosclerosis. In the majority of cases the antigen component of the immune complex was lipoprotein of very low density. After dissociation of the complex at acid pH, immunoglobulin G was isolated, which was identified by double immunodiffusion in agar gel; the immunoglobulin reacted in RBS both with autological and, in some cases, with isological lipoproteins.", "contents": "[Detection of autoimmune lipoprotein--antibody complex in human plasma and aortic wall]. An immune complex of lipoprotein-antibody was found in human blood plasma and in tissue liquid of aorta, impaired by atherosclerosis. In the majority of cases the antigen component of the immune complex was lipoprotein of very low density. After dissociation of the complex at acid pH, immunoglobulin G was isolated, which was identified by double immunodiffusion in agar gel; the immunoglobulin reacted in RBS both with autological and, in some cases, with isological lipoproteins."}
{"id": "PMID:210597", "title": "Immunization against swine influenza in the Yale University Community.", "content": "Nineteen percent of the approximately 30,000 members of the Yale community aged 18 through 59 received swine influenza monovalent vaccine (A/New Jersey/1976) during the three days of a mass immunization program in Nov. 1976. Based on 1508 card questionnaires received, 71.2 percent of the vaccine recipients experienced a sore arm, 23.4 percent headache, 13.4 percent chilliness, and 9.7 percent feverishness or fever. The sore arm was judged as severe in 5.9 percent as was the headache in 4.2 percent. Other reactions were regarded as severe in less than 2 percent. All reactions were reported more commonly by women than mean and all decreased with age.Serologic tests carried out at the start of the immunization period revealed that influenza A/New Jersey/1976 antibody was absent from 78.6 percent of the recipients; almost all persons under 25 lacked this antibody. A significant antibody rise occurred in 78.3 percent of those receiving a single dose of monovalent vaccine. Somewhat better antibody responses occurred in 36-59 year olds than in those age 17-25 (84.9 vs 75.5 percent); the geometric mean antibody titer was also much higher (1:136.8 vs 1:31.2). However, the presence of pre-existing homologous antibody did not significantly improve the antibody response to the vaccine. Cross-reacting antibody rises to A/Victoria/1975 were found in 16.2 percent of the recipients of monovalent vaccine.", "contents": "Immunization against swine influenza in the Yale University Community. Nineteen percent of the approximately 30,000 members of the Yale community aged 18 through 59 received swine influenza monovalent vaccine (A/New Jersey/1976) during the three days of a mass immunization program in Nov. 1976. Based on 1508 card questionnaires received, 71.2 percent of the vaccine recipients experienced a sore arm, 23.4 percent headache, 13.4 percent chilliness, and 9.7 percent feverishness or fever. The sore arm was judged as severe in 5.9 percent as was the headache in 4.2 percent. Other reactions were regarded as severe in less than 2 percent. All reactions were reported more commonly by women than mean and all decreased with age.Serologic tests carried out at the start of the immunization period revealed that influenza A/New Jersey/1976 antibody was absent from 78.6 percent of the recipients; almost all persons under 25 lacked this antibody. A significant antibody rise occurred in 78.3 percent of those receiving a single dose of monovalent vaccine. Somewhat better antibody responses occurred in 36-59 year olds than in those age 17-25 (84.9 vs 75.5 percent); the geometric mean antibody titer was also much higher (1:136.8 vs 1:31.2). However, the presence of pre-existing homologous antibody did not significantly improve the antibody response to the vaccine. Cross-reacting antibody rises to A/Victoria/1975 were found in 16.2 percent of the recipients of monovalent vaccine."}
{"id": "PMID:210603", "title": "[Carotid body tumors and their operative problems (author's transl)].", "content": "Exstirpation of a neck tumor as an outpatient procedure became troublesome (bleeding). The surgeon had not realised the nature of the tumor.", "contents": "[Carotid body tumors and their operative problems (author's transl)]. Exstirpation of a neck tumor as an outpatient procedure became troublesome (bleeding). The surgeon had not realised the nature of the tumor."}
{"id": "PMID:210604", "title": "[Selection of newborns with birth injuries for after care in a special session].", "content": "Selection of birth-traumatical injured newborns for follow-up with special care.--Premature newborns most will be in a special care during infancy and childhood. For all the mature infants this way is to expensive. We publish a compilation of abnormal neurological findings suitable for selecting with high risk of birth traumatical induced brain damage. The risk-group contains about 5% of all mature newborns. This number is small enough for a high expense within the bounds of the common care for mother and child.", "contents": "[Selection of newborns with birth injuries for after care in a special session]. Selection of birth-traumatical injured newborns for follow-up with special care.--Premature newborns most will be in a special care during infancy and childhood. For all the mature infants this way is to expensive. We publish a compilation of abnormal neurological findings suitable for selecting with high risk of birth traumatical induced brain damage. The risk-group contains about 5% of all mature newborns. This number is small enough for a high expense within the bounds of the common care for mother and child."}
{"id": "PMID:210605", "title": "[Clinical aspects of trophoblastic tumors].", "content": "Trophoblastic tumors are among the rare diseases in this country. The most important clinical aspects are demonstrated by references and personal experiences in the treatment of trophoblastic tumors. In many countries (SU, USA, GB, Japan) the treatment of trophoblastic tumors has been centralized.--The therapeutical strategy is based on histology, stage and other important prognostic factors. Most important is chemotherapy with antineoplastic substances. Surgery and radiation are to be used only under appropriate indication. After treatment the control of the HCG-values by radioimmunassay is of high importance for the early diagnosis of relapse.--All facts demonstrate, that also in the GDR a stronger centralization of the treatment of trophoblastic tumors should be attained.", "contents": "[Clinical aspects of trophoblastic tumors]. Trophoblastic tumors are among the rare diseases in this country. The most important clinical aspects are demonstrated by references and personal experiences in the treatment of trophoblastic tumors. In many countries (SU, USA, GB, Japan) the treatment of trophoblastic tumors has been centralized.--The therapeutical strategy is based on histology, stage and other important prognostic factors. Most important is chemotherapy with antineoplastic substances. Surgery and radiation are to be used only under appropriate indication. After treatment the control of the HCG-values by radioimmunassay is of high importance for the early diagnosis of relapse.--All facts demonstrate, that also in the GDR a stronger centralization of the treatment of trophoblastic tumors should be attained."}
{"id": "PMID:210602", "title": "[Basic studies on chronic polyarthritis as a collagen-autoimmune disease].", "content": "Clinical and experimental data establishing a hypothesis about rheumatoid arthritis (RA) as a collagen auto-immune disease are reviewed, beginning with the demonstration of rheumatoid synovial collagenase, the demonstration of collagen antibodies in the serum and the synovial fluid of patients with RA, the demonstration of collagen inclusion bodies and collagen-anticollagen immune complexes in synovial fluid cells and the synovial fluid of patients with RA, and leading to the in vitro demonstration of the inflammatory effect of such complexes, and the induction of experimental arthritis by these complexes. Each section contains tabular summaries of various investigations. Finally, a relation between these observations and the conclusions deduced from them and the appearance of rheumatoid factors in RA and the pathogenic effect of rheumatoid factor - gammaglobulin aggregates is considered.", "contents": "[Basic studies on chronic polyarthritis as a collagen-autoimmune disease]. Clinical and experimental data establishing a hypothesis about rheumatoid arthritis (RA) as a collagen auto-immune disease are reviewed, beginning with the demonstration of rheumatoid synovial collagenase, the demonstration of collagen antibodies in the serum and the synovial fluid of patients with RA, the demonstration of collagen inclusion bodies and collagen-anticollagen immune complexes in synovial fluid cells and the synovial fluid of patients with RA, and leading to the in vitro demonstration of the inflammatory effect of such complexes, and the induction of experimental arthritis by these complexes. Each section contains tabular summaries of various investigations. Finally, a relation between these observations and the conclusions deduced from them and the appearance of rheumatoid factors in RA and the pathogenic effect of rheumatoid factor - gammaglobulin aggregates is considered."}
{"id": "PMID:210607", "title": "[Noradrenaline and glycogen content and the activity of several enzymes of carbohydrate metabolism in normal, embryonic, and partly denervated livers and in hepatomas of the rat].", "content": "The noradrenaline and glycogen contents as well as hexokinase, glucokinase and glucose-6-phosphatase activities were determined in normal, embryonic and partially denervated (bilateral dissection of the Nervus splanchnicus or Nervus vagus) rat liver and in two transplantable hepatomas. In embryonic liver and hepatomas a strong decrease or complete loss of noradrenaline and glycogen levels and glucokinase and glucose-6-phosphatase activities is demonstrable as compared to the livers of adult animals, while the hexokinase activity is enhanced. Following bilateral splanchnicotomy the glycogen content and hexokinase activity are enhanced; the glucose-6-phosphatase activity is reduced, and the liver does not contain any noradrenaline. Bilateral vagotomy causes decrease of the glycogen content, of the hexokinase and glucokinase activities and an enhancement of glucose-6-phosphatase activity. The results lend support to the idea of antagonistic action of the sympathetic and parasympathetic nervous systems upon several partial reactions of carbohydrate metabolism of liver. In addition, it can be assumed that the alterations of the carbohydrate metabolism demonstrable in hepatomas as compared to normal liver are not solely attributable to disturbance or breakdown of the nervous regulation.", "contents": "[Noradrenaline and glycogen content and the activity of several enzymes of carbohydrate metabolism in normal, embryonic, and partly denervated livers and in hepatomas of the rat]. The noradrenaline and glycogen contents as well as hexokinase, glucokinase and glucose-6-phosphatase activities were determined in normal, embryonic and partially denervated (bilateral dissection of the Nervus splanchnicus or Nervus vagus) rat liver and in two transplantable hepatomas. In embryonic liver and hepatomas a strong decrease or complete loss of noradrenaline and glycogen levels and glucokinase and glucose-6-phosphatase activities is demonstrable as compared to the livers of adult animals, while the hexokinase activity is enhanced. Following bilateral splanchnicotomy the glycogen content and hexokinase activity are enhanced; the glucose-6-phosphatase activity is reduced, and the liver does not contain any noradrenaline. Bilateral vagotomy causes decrease of the glycogen content, of the hexokinase and glucokinase activities and an enhancement of glucose-6-phosphatase activity. The results lend support to the idea of antagonistic action of the sympathetic and parasympathetic nervous systems upon several partial reactions of carbohydrate metabolism of liver. In addition, it can be assumed that the alterations of the carbohydrate metabolism demonstrable in hepatomas as compared to normal liver are not solely attributable to disturbance or breakdown of the nervous regulation."}
{"id": "PMID:210608", "title": "Serum somatomedin A in growth retarded children.", "content": "The levels of serum somatomedin A were determined in 59 growth retarded Japanese children by a radioreceptor assay. Low levels were found in 10 children with growth hormone (GH) deficiency and 7 children with relative GH deficiency with means of 0.26 +/- 0.48 +/- 0.04 U/ml, respectively. Serum somatomedin A levels in 42 retarded children with normal growth hormone levels were within the range of normal adults, and did not correlate with degree of short stature. Significant increases of somatomedin A after hGH administration were found in children with growth hormone deficiency but not in children with normal growth hormone. These results show that determination of somatomedin A in serum corelates well with the state of growth hormone secretion, and is of great importance in the selection of patients for treatment with human growth hormone.", "contents": "Serum somatomedin A in growth retarded children. The levels of serum somatomedin A were determined in 59 growth retarded Japanese children by a radioreceptor assay. Low levels were found in 10 children with growth hormone (GH) deficiency and 7 children with relative GH deficiency with means of 0.26 +/- 0.48 +/- 0.04 U/ml, respectively. Serum somatomedin A levels in 42 retarded children with normal growth hormone levels were within the range of normal adults, and did not correlate with degree of short stature. Significant increases of somatomedin A after hGH administration were found in children with growth hormone deficiency but not in children with normal growth hormone. These results show that determination of somatomedin A in serum corelates well with the state of growth hormone secretion, and is of great importance in the selection of patients for treatment with human growth hormone."}
{"id": "PMID:210609", "title": "Changes in cyclic nucleotides of rat thyroid by chronic administration of LATS and TSH.", "content": "The effects of LATS and TSH on the cyclic nucleotide content and enzymatic activity in rat thyroid was observed during the continuous administration of LATS or TSH for 6 days. Serum T4 and T3 levels were increased significantly compared with the saline controls. The cyclic nucleotide (cAMP and cGMP) levels and enzyme activities per wet weight of tissue were determined. The thyroid weight in both the LATS and TSH groups increased approximately two-fold, but cAMP and cGMP content per wet weight did not significantly change. Neither cyclic nucleotide showed any significant change in plasma. The cAMP-PDE activity in the thyroid significantly increased in both the LATS and TSH groups, but the cGMP-PDE activity was unchanged. Neither was cyclic nucleotide-PDE activity changed in the plasma. The ATPase activity in the thyroid increased markedly in both the LATS and TSH groups, while 5'-nucleotidase activity did not change. These data suggest that LATS and TSH appear to have a stimulatory effect on the metabolism of cAMP, but do not affect the metabolism of cGMP.", "contents": "Changes in cyclic nucleotides of rat thyroid by chronic administration of LATS and TSH. The effects of LATS and TSH on the cyclic nucleotide content and enzymatic activity in rat thyroid was observed during the continuous administration of LATS or TSH for 6 days. Serum T4 and T3 levels were increased significantly compared with the saline controls. The cyclic nucleotide (cAMP and cGMP) levels and enzyme activities per wet weight of tissue were determined. The thyroid weight in both the LATS and TSH groups increased approximately two-fold, but cAMP and cGMP content per wet weight did not significantly change. Neither cyclic nucleotide showed any significant change in plasma. The cAMP-PDE activity in the thyroid significantly increased in both the LATS and TSH groups, but the cGMP-PDE activity was unchanged. Neither was cyclic nucleotide-PDE activity changed in the plasma. The ATPase activity in the thyroid increased markedly in both the LATS and TSH groups, while 5'-nucleotidase activity did not change. These data suggest that LATS and TSH appear to have a stimulatory effect on the metabolism of cAMP, but do not affect the metabolism of cGMP."}
{"id": "PMID:210612", "title": "Peripheral cryoglobulinemic neuropathy in a patient with Gaucher's disease.", "content": "Cryoglobulinemia with peripheral cryoglobulinemic neuropathy is reported in a patient with Gaucher's disease. To the best of our knowledge, a similar relationship has not been previously described. The question whether the cryoglobulinemic neuropathy in this patient is related to Gaucher's disease, or is a mere coincidence, is discussed.", "contents": "Peripheral cryoglobulinemic neuropathy in a patient with Gaucher's disease. Cryoglobulinemia with peripheral cryoglobulinemic neuropathy is reported in a patient with Gaucher's disease. To the best of our knowledge, a similar relationship has not been previously described. The question whether the cryoglobulinemic neuropathy in this patient is related to Gaucher's disease, or is a mere coincidence, is discussed."}
{"id": "PMID:210613", "title": "[The age dependent distribution and activity of enzyme metabolism in the humeral epiphysis].", "content": "In the chondrocytes of the humerus epiphysis and of the articular cartilage of newborn, 8-, 30-, and 60-day-old albino rats, cytochrome c oxidase, arylsulfatase and carbonate dehydratase activity was found. In the transformation zone, the column cartilage and the proximal hypertrophic cells of 30- and 60-day-old animals, cytochrome c oxidase and arylsulfatase are distinctly present. The reaction of carbonate dehydratase is most pronounced in these cell regions of 8-day-old animals. In the mineralization zone we found only small activity of the investigated enzymes. The cells of the opening zone of all age groups demonstrate an additional activity. In the articular cartilage the cytochrome c oxidase is very distinct. The carbonate dehydratase follows with variable reduction and finally the arylsulfatase with only small activity.", "contents": "[The age dependent distribution and activity of enzyme metabolism in the humeral epiphysis]. In the chondrocytes of the humerus epiphysis and of the articular cartilage of newborn, 8-, 30-, and 60-day-old albino rats, cytochrome c oxidase, arylsulfatase and carbonate dehydratase activity was found. In the transformation zone, the column cartilage and the proximal hypertrophic cells of 30- and 60-day-old animals, cytochrome c oxidase and arylsulfatase are distinctly present. The reaction of carbonate dehydratase is most pronounced in these cell regions of 8-day-old animals. In the mineralization zone we found only small activity of the investigated enzymes. The cells of the opening zone of all age groups demonstrate an additional activity. In the articular cartilage the cytochrome c oxidase is very distinct. The carbonate dehydratase follows with variable reduction and finally the arylsulfatase with only small activity."}
{"id": "PMID:210614", "title": "Comparative histochemical study of the enzyme changes in the ovary and uterus of mammals with special references to steroidogenesis.", "content": "A comparative study of the enzymes delta5-3beta-HSD, cytochrome oxidase and peroxidase has been made in the ovaries and uterus of mammals (mouse, guinea pig, cat and dog) during various reproductive phases. The granulosa cells of developing follicles, hypertrophied interstitial cells of thecal origin and the luteal cells show intense delta5-3beta-HSD and cytochrome oxidase activity. Peroxidases are found to be present in the corpus luteum and the epithelial cords of thecal origin. delta5-3beta-HSD and cytochrome oxidase activity is localized to the endometrium and myometrium of mature and pregnant uterus of mouse and guinea pig, while peroxidase is seen only in the decidua and endometrial glands of pregnant animals. The significance of these enzymes is discussed in relation to the cellular basis of luteinization and steroid hormone synthesis.", "contents": "Comparative histochemical study of the enzyme changes in the ovary and uterus of mammals with special references to steroidogenesis. A comparative study of the enzymes delta5-3beta-HSD, cytochrome oxidase and peroxidase has been made in the ovaries and uterus of mammals (mouse, guinea pig, cat and dog) during various reproductive phases. The granulosa cells of developing follicles, hypertrophied interstitial cells of thecal origin and the luteal cells show intense delta5-3beta-HSD and cytochrome oxidase activity. Peroxidases are found to be present in the corpus luteum and the epithelial cords of thecal origin. delta5-3beta-HSD and cytochrome oxidase activity is localized to the endometrium and myometrium of mature and pregnant uterus of mouse and guinea pig, while peroxidase is seen only in the decidua and endometrial glands of pregnant animals. The significance of these enzymes is discussed in relation to the cellular basis of luteinization and steroid hormone synthesis."}
{"id": "PMID:210616", "title": "Progression of a structural scoliosis during treatment with growth hormone. A case report.", "content": "A diagnosis of panhypopituitarism was made in an infantile male at the age of 22. Skeletal age was estimated to be 14 years. Thyroxin, corticosteroid and later testosterone was administered. Growth hormone was given initially over a period of ten weeks and later for two and a half years. The standing height increased from 143 to 158.5 cm. During periods of growth induced by growth hormone a progression of a thoracic scoliosis from 15 degrees to 62 degrees was observed. In this case growth hormone or the associated substances seem to be the more probable cause of the progression of scoliosis than growth rate per se.", "contents": "Progression of a structural scoliosis during treatment with growth hormone. A case report. A diagnosis of panhypopituitarism was made in an infantile male at the age of 22. Skeletal age was estimated to be 14 years. Thyroxin, corticosteroid and later testosterone was administered. Growth hormone was given initially over a period of ten weeks and later for two and a half years. The standing height increased from 143 to 158.5 cm. During periods of growth induced by growth hormone a progression of a thoracic scoliosis from 15 degrees to 62 degrees was observed. In this case growth hormone or the associated substances seem to be the more probable cause of the progression of scoliosis than growth rate per se."}
{"id": "PMID:210617", "title": "Cyclic AMP and insulin release.", "content": "The role of cyclic adenosine-3',5'-monophosphate (cAMP) for insulin secretion has been investigated. In isolated islets of Langerhans from the rat, glucose increases cAMP concomitant with insulin secretion. Stimulation of these two parameters is likewise reversible in parallel. The minimal and maximal concentrations of glucose eliciting cAMP and insulin responses are similar. Isomers and epimers of glucose influence insulin and cAMP in a parallel fashion as do sulfonylurea compounds (tolbutamide and glibenclamide). On the contrary, the time-dependent potentiation of glucose-induced insulin secretion is not accompanied by gross changes in cAMP. Reciprocally, in the absence of glucose islet cAMP can be markedly elevated by other agents (methyl xanthines, cholera toxin) without major insulin responses. The results indicate that metabolism of cAMP in the beta-cell is intimately linked to the glucose (and sulfonylurea) action on insulin secretion, although other factors influenced by the hexose are also necessary for the release process. The finding that the cAMP response is impaired in fasting, during the neonatal period and in diabetes mellitus (in the Chinese hamster) suggests an important role for the nucleotide in physiological and pathophysiological states characterized by decreased insulin release.", "contents": "Cyclic AMP and insulin release. The role of cyclic adenosine-3',5'-monophosphate (cAMP) for insulin secretion has been investigated. In isolated islets of Langerhans from the rat, glucose increases cAMP concomitant with insulin secretion. Stimulation of these two parameters is likewise reversible in parallel. The minimal and maximal concentrations of glucose eliciting cAMP and insulin responses are similar. Isomers and epimers of glucose influence insulin and cAMP in a parallel fashion as do sulfonylurea compounds (tolbutamide and glibenclamide). On the contrary, the time-dependent potentiation of glucose-induced insulin secretion is not accompanied by gross changes in cAMP. Reciprocally, in the absence of glucose islet cAMP can be markedly elevated by other agents (methyl xanthines, cholera toxin) without major insulin responses. The results indicate that metabolism of cAMP in the beta-cell is intimately linked to the glucose (and sulfonylurea) action on insulin secretion, although other factors influenced by the hexose are also necessary for the release process. The finding that the cAMP response is impaired in fasting, during the neonatal period and in diabetes mellitus (in the Chinese hamster) suggests an important role for the nucleotide in physiological and pathophysiological states characterized by decreased insulin release."}
{"id": "PMID:210618", "title": "Immunohistochemical identification of actomyosin-containing (myoepithelial) cells in non-neoplastic and neoplastic tissues.", "content": "Actomyosin-containing cells in both non-neoplastic and neoplastic tissues of the salivary gland, lung, breast and some other organs were studied by immunofluorescent microscopy using antiactomyosin rabbit serum. In the breast, myoepithelial-like cells with positive immunofluorescence in the cytoplasm were observed not only in sclerosing adenosis and fibroadenoma but also in scirrhous and medullary-tubular duct carcinomas. No positive cells were observed in medullary carcinomas with lymphoid infiltration. The actomyosin positive cells were also seen at the outer layer of tubules of \"mixed tumors\" and of cell nests in adenoid cystic carcinoma and in myoepithelioma of the salivary gland, but not in the metaplastic squamous cells or in the cells of myxomatous and chondroid areas of \"mixed tumor\". In carcinoma of the lung, actomyosin-positive cells were observed in adenoid cystic carcinomas and adenocarcinoma of the bronchial gland type, but they were not seen in squamous cell carcinomas or papillary adenocarcinomas. It was concluded that the actomysoin-containing cells with structural appearances of myoepithelial cells in a variety of tumors were neoplastic myoepithelial cells.", "contents": "Immunohistochemical identification of actomyosin-containing (myoepithelial) cells in non-neoplastic and neoplastic tissues. Actomyosin-containing cells in both non-neoplastic and neoplastic tissues of the salivary gland, lung, breast and some other organs were studied by immunofluorescent microscopy using antiactomyosin rabbit serum. In the breast, myoepithelial-like cells with positive immunofluorescence in the cytoplasm were observed not only in sclerosing adenosis and fibroadenoma but also in scirrhous and medullary-tubular duct carcinomas. No positive cells were observed in medullary carcinomas with lymphoid infiltration. The actomyosin positive cells were also seen at the outer layer of tubules of \"mixed tumors\" and of cell nests in adenoid cystic carcinoma and in myoepithelioma of the salivary gland, but not in the metaplastic squamous cells or in the cells of myxomatous and chondroid areas of \"mixed tumor\". In carcinoma of the lung, actomyosin-positive cells were observed in adenoid cystic carcinomas and adenocarcinoma of the bronchial gland type, but they were not seen in squamous cell carcinomas or papillary adenocarcinomas. It was concluded that the actomysoin-containing cells with structural appearances of myoepithelial cells in a variety of tumors were neoplastic myoepithelial cells."}
{"id": "PMID:210619", "title": "A freeze-fracture study of tubular myelin in fetal rabbit lung.", "content": "A freeze-fracture replication study was undertaken to clarify the relationship between intracellular lamellar bodies of type II alveolar epithelial cells and intra-alveolar contents in late gestation rabbit fetuses. The interior of the inclusion bodies was composed of multiple stacks and/or whorls of membranes devoid of membrane-associated particles, while the limiting membrane of intracellular lamellar inclusion bodies was studied with membrane-associated particles of 150A diameter. The intra-alveolar contents were comprised of two components; spherical bodies, and tubular elements. Spherical bodies were identical to the internal contents of the lamellar bodies and also were devoid of membrane-associated particles. Tubular elements mostly appeared rectangular on cross-fractured faces, but triangular and hexagonal forms could also be seen. These tubules rested on the surfaces of the spherical bodies and appeared to be formed of the outer lipid monolayer of spherical bodies. The present observations suggest that the tubular element of the alveolar contents is formed through the interaction between the discharged lamellar body content and the alveolar fluid.", "contents": "A freeze-fracture study of tubular myelin in fetal rabbit lung. A freeze-fracture replication study was undertaken to clarify the relationship between intracellular lamellar bodies of type II alveolar epithelial cells and intra-alveolar contents in late gestation rabbit fetuses. The interior of the inclusion bodies was composed of multiple stacks and/or whorls of membranes devoid of membrane-associated particles, while the limiting membrane of intracellular lamellar inclusion bodies was studied with membrane-associated particles of 150A diameter. The intra-alveolar contents were comprised of two components; spherical bodies, and tubular elements. Spherical bodies were identical to the internal contents of the lamellar bodies and also were devoid of membrane-associated particles. Tubular elements mostly appeared rectangular on cross-fractured faces, but triangular and hexagonal forms could also be seen. These tubules rested on the surfaces of the spherical bodies and appeared to be formed of the outer lipid monolayer of spherical bodies. The present observations suggest that the tubular element of the alveolar contents is formed through the interaction between the discharged lamellar body content and the alveolar fluid."}
{"id": "PMID:210620", "title": "Brain tumors induced in hamsters by intracerebral inoculation of SR-RSV-infected embryonic brain cells.", "content": "Brain tumors were induced in Syrian hamsters by intracerebral inoculation of brain cells which were obtained from 12-day old syngeneic hamster and infected with Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) in vitro. A total of 212 tumors were developed in all 25 recipients within 19 to 125 days after transplantation. On the basis of light and electron microscopic study, they were classified into four main groups: astrocytoma (45.8%), pleomorphic glioma (50.0%), sarcoma (3.8%), unclassified (0.4%). The morphological features of these tumors were described, and the advantages of this brain tumor model were discussed.", "contents": "Brain tumors induced in hamsters by intracerebral inoculation of SR-RSV-infected embryonic brain cells. Brain tumors were induced in Syrian hamsters by intracerebral inoculation of brain cells which were obtained from 12-day old syngeneic hamster and infected with Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) in vitro. A total of 212 tumors were developed in all 25 recipients within 19 to 125 days after transplantation. On the basis of light and electron microscopic study, they were classified into four main groups: astrocytoma (45.8%), pleomorphic glioma (50.0%), sarcoma (3.8%), unclassified (0.4%). The morphological features of these tumors were described, and the advantages of this brain tumor model were discussed."}
{"id": "PMID:210621", "title": "An autopsy case of cholangiocarcinoma with hypercalcemia.", "content": "Au autopsy case of cholangiocarcinoma which showed clinically hypercalcemia and hypophosphatemia without bone metastases is presented in this report. Although parathyroid hormone (PTH)-like substance of 520 ng/g. dry weight was measured in neoplastic tissue by the radioimmunoassay, membrane-limited secretory granules as those of parathyroid gland were not found in the fine structure. The significance of an existence of secretory granules in ectopic PTH producing tumor is discussed.", "contents": "An autopsy case of cholangiocarcinoma with hypercalcemia. Au autopsy case of cholangiocarcinoma which showed clinically hypercalcemia and hypophosphatemia without bone metastases is presented in this report. Although parathyroid hormone (PTH)-like substance of 520 ng/g. dry weight was measured in neoplastic tissue by the radioimmunoassay, membrane-limited secretory granules as those of parathyroid gland were not found in the fine structure. The significance of an existence of secretory granules in ectopic PTH producing tumor is discussed."}
{"id": "PMID:210622", "title": "Crystalline structures in human pancreatic beta cell adenoma.", "content": "An electron microscopic observation on a pancreatic tumor removed from a 34-year-old woman revealed the fine structural morphology of a functional beta cell adenoma. Characteristic PAS positive crystalline structures were frequently observed in the cytoplasm of the tumor cells. They were not bounded by a membrane and had a rectangular or irregular hexagonal shape. Highly regular patterns were seen as such as lattice or honeycomb and parallel ripple structures. They are similar to the Reinke's crystal or crystalline structures reported in human hepatocytes suffering from several different diseases and considered as a protein-carbohydrate complex. Occasionally, small paracrystalline structures appeared to indicate an immature type of these structures in the opaque fine fibrillar mass. Crystalline or paracrystalline structures were not detected in the normal pancreatic tissue removed with the tumor from the patient.", "contents": "Crystalline structures in human pancreatic beta cell adenoma. An electron microscopic observation on a pancreatic tumor removed from a 34-year-old woman revealed the fine structural morphology of a functional beta cell adenoma. Characteristic PAS positive crystalline structures were frequently observed in the cytoplasm of the tumor cells. They were not bounded by a membrane and had a rectangular or irregular hexagonal shape. Highly regular patterns were seen as such as lattice or honeycomb and parallel ripple structures. They are similar to the Reinke's crystal or crystalline structures reported in human hepatocytes suffering from several different diseases and considered as a protein-carbohydrate complex. Occasionally, small paracrystalline structures appeared to indicate an immature type of these structures in the opaque fine fibrillar mass. Crystalline or paracrystalline structures were not detected in the normal pancreatic tissue removed with the tumor from the patient."}
{"id": "PMID:210623", "title": "Protein kinases in rat testes. Subcellular distribution of the enzyme and endogenous substrates.", "content": "The subcellular distribution of cAMP dependent and independent protein kinases (Pr K) has been studied in rat tests. The enzymatic activity was preferentially located in the cytosol. In all fractions mature animals have higher specific activity. The localization of endogenous protein substrates of Pr K was investigated using cytosol as an enzymatic source. The best endogenous substrate for the cAMP dependent Pr K seemed to be localized in the microsomal fraction. The rate of protein phosphorylation in the  testicular subcellular fractions was examined by in vitro incubation with 32P-orthophosphate. The nuclear fractions have the highest specific radioactivity.", "contents": "Protein kinases in rat testes. Subcellular distribution of the enzyme and endogenous substrates. The subcellular distribution of cAMP dependent and independent protein kinases (Pr K) has been studied in rat tests. The enzymatic activity was preferentially located in the cytosol. In all fractions mature animals have higher specific activity. The localization of endogenous protein substrates of Pr K was investigated using cytosol as an enzymatic source. The best endogenous substrate for the cAMP dependent Pr K seemed to be localized in the microsomal fraction. The rate of protein phosphorylation in the  testicular subcellular fractions was examined by in vitro incubation with 32P-orthophosphate. The nuclear fractions have the highest specific radioactivity."}
{"id": "PMID:210624", "title": "Mitochondrial production of hydrogen peroxide in Saccharomyces cerevisiae.", "content": "Intact mitochondria isolated from bakers' yeast and showing respiratory control by ADP, released H2O2 to the suspending medium at rates of 1.2.2.2 nmol/min per mg of protein depending on the mitochondrial metabolic condition. Release of H2O2 from mitochondria increased 1.3 times in swollen mitochondria and 1.2 times after osmotic shock, i.e., when the outer membrane was damaged. Under physiological conditions, yeast cytochrome c peroxidase, mainly  located in the intermembrane space, utilized about 53-55% of the H2O2 generated by the respiratory chain at the inner membrane, partially preventing H2O2 diffusion to the cytosol. Apparently, the outer mitochondrial membrane was highly permeable to H2O2. It is claimed that the risk of cell injury due to H2O2, O-2 and HO is slightly higher in the stationary phase than in the logarithmic phase of growth.", "contents": "Mitochondrial production of hydrogen peroxide in Saccharomyces cerevisiae. Intact mitochondria isolated from bakers' yeast and showing respiratory control by ADP, released H2O2 to the suspending medium at rates of 1.2.2.2 nmol/min per mg of protein depending on the mitochondrial metabolic condition. Release of H2O2 from mitochondria increased 1.3 times in swollen mitochondria and 1.2 times after osmotic shock, i.e., when the outer membrane was damaged. Under physiological conditions, yeast cytochrome c peroxidase, mainly  located in the intermembrane space, utilized about 53-55% of the H2O2 generated by the respiratory chain at the inner membrane, partially preventing H2O2 diffusion to the cytosol. Apparently, the outer mitochondrial membrane was highly permeable to H2O2. It is claimed that the risk of cell injury due to H2O2, O-2 and HO is slightly higher in the stationary phase than in the logarithmic phase of growth."}
{"id": "PMID:210626", "title": "Fructose metabolism in plants. Isolation and properties of pea seed frucktokinase.", "content": "Fructokinase from pea (Pisum sativum L.) seed has purified 100-fold. The enzyme required reduced sulfhydryl groups for activity. It also exhibits an absolute requirement for potassium ions (Km = 3 mM) and is unstable when not stored with a high concentration of potassium ions. The isoelectric point of the enzyme is 4.7 and it has a molecular weight of 44 000 +/- 700 daltons as determined  by molecular sieve chromatography and sedimentation velocity techniques. A Hill plot of the potassium ion data suggests that two potassium sites are present on the enzyme. The MgATP saturation curve was non-Michaelis-Menten with a slight positive cooperativity. Pea seed fructokinase is highly specific for fructose and ATP. A comparison of pea seed fructokinase properties and those of liver and bacterial origin is presented.", "contents": "Fructose metabolism in plants. Isolation and properties of pea seed frucktokinase. Fructokinase from pea (Pisum sativum L.) seed has purified 100-fold. The enzyme required reduced sulfhydryl groups for activity. It also exhibits an absolute requirement for potassium ions (Km = 3 mM) and is unstable when not stored with a high concentration of potassium ions. The isoelectric point of the enzyme is 4.7 and it has a molecular weight of 44 000 +/- 700 daltons as determined  by molecular sieve chromatography and sedimentation velocity techniques. A Hill plot of the potassium ion data suggests that two potassium sites are present on the enzyme. The MgATP saturation curve was non-Michaelis-Menten with a slight positive cooperativity. Pea seed fructokinase is highly specific for fructose and ATP. A comparison of pea seed fructokinase properties and those of liver and bacterial origin is presented."}
{"id": "PMID:210627", "title": "Polymeric structure of a cyclic adenosine 3', 5',-monophosphate dependent protein kinase from the dimorphic fungus Mucor rouXII.", "content": "Adenosine 3', 5'-monophosphate (cAMP) dependent protein kinase from yeast cells of Mucor rouxii was partially purified and examined by sedimentation in sucrose density gradients. In the presence of histone and cAMP this procedure allowed the separation of the catalytic moiety from the cAMP binding activity, indicating that the enzyme had dissociated into subunits. The dissociation was accompanied by conversion of the enzyme activity from a cAMP dependent to a cAMP independent form.", "contents": "Polymeric structure of a cyclic adenosine 3', 5',-monophosphate dependent protein kinase from the dimorphic fungus Mucor rouXII. Adenosine 3', 5'-monophosphate (cAMP) dependent protein kinase from yeast cells of Mucor rouxii was partially purified and examined by sedimentation in sucrose density gradients. In the presence of histone and cAMP this procedure allowed the separation of the catalytic moiety from the cAMP binding activity, indicating that the enzyme had dissociated into subunits. The dissociation was accompanied by conversion of the enzyme activity from a cAMP dependent to a cAMP independent form."}
{"id": "PMID:210628", "title": "Specific binding of human and bovine growth hormones to hypophysectomized rat hepatocytes.", "content": "Specific binding of 125I-HGH and 125I-bGH was obtained in hypophysectomized rat liver cells. Two types of somatogenic receptors were found with apparent dissociation constants of 4.2 x 10(8) M-1 and 1.7 x 10(7) M-1. The number of sites for the higher and lower affinity receptors were: 1 x 10(4) and 6 x 10(3), respectively. Human, bovine and equine growth hormones appear to bind to liver cells with equal affinity, while ovine prolactin needs at least a two-order-magnitude greater concentration to displace 125I-bGH. A parallelism between biological activity and binding data was observed.", "contents": "Specific binding of human and bovine growth hormones to hypophysectomized rat hepatocytes. Specific binding of 125I-HGH and 125I-bGH was obtained in hypophysectomized rat liver cells. Two types of somatogenic receptors were found with apparent dissociation constants of 4.2 x 10(8) M-1 and 1.7 x 10(7) M-1. The number of sites for the higher and lower affinity receptors were: 1 x 10(4) and 6 x 10(3), respectively. Human, bovine and equine growth hormones appear to bind to liver cells with equal affinity, while ovine prolactin needs at least a two-order-magnitude greater concentration to displace 125I-bGH. A parallelism between biological activity and binding data was observed."}
{"id": "PMID:210630", "title": "Characteristics of reinnervation of skeletal muscle in the rat.", "content": "Both extra and intracellular fibrillation activity recorded in vivo was studied during nerve-muscle reinnervation, in control rats and in rats treated with actinomycin D. The study was performed at different times after nerve crushing. End-plate potentials (EPP's) and muscle action potentials were always present on the eleventh day after denervation. Fibrillation activity recorded extracellularly began to decrease on the twelfth day. Intracellular fibrillation activity was found in single muscle cells simultaneously with evoked EPP's muscle action potentials. In early stages of reinnervation two EPP's were recorded in a single muscle cell, thus indicating double innervation. When presynaptic action of actinomycin D was tested no changes were found in miniature end-plate potential frequency. Muscles from rats submitted to early treatment with actinomycin D did not show any delay in the onset of reinnervation. In muscles from rats submitted to late treatment, extrasynaptic sensitivity to acetylcholine was ascertained regardless of the presence of functional reinnervation. Chronic stimulation of denervated muscles, while suppressing fibrillation activity, did not interfere with reinnervation. The results reported suggest that reinnervation can take place independently of fibrillation activity as well as of extrasynaptic receptors.", "contents": "Characteristics of reinnervation of skeletal muscle in the rat. Both extra and intracellular fibrillation activity recorded in vivo was studied during nerve-muscle reinnervation, in control rats and in rats treated with actinomycin D. The study was performed at different times after nerve crushing. End-plate potentials (EPP's) and muscle action potentials were always present on the eleventh day after denervation. Fibrillation activity recorded extracellularly began to decrease on the twelfth day. Intracellular fibrillation activity was found in single muscle cells simultaneously with evoked EPP's muscle action potentials. In early stages of reinnervation two EPP's were recorded in a single muscle cell, thus indicating double innervation. When presynaptic action of actinomycin D was tested no changes were found in miniature end-plate potential frequency. Muscles from rats submitted to early treatment with actinomycin D did not show any delay in the onset of reinnervation. In muscles from rats submitted to late treatment, extrasynaptic sensitivity to acetylcholine was ascertained regardless of the presence of functional reinnervation. Chronic stimulation of denervated muscles, while suppressing fibrillation activity, did not interfere with reinnervation. The results reported suggest that reinnervation can take place independently of fibrillation activity as well as of extrasynaptic receptors."}
{"id": "PMID:210632", "title": "Response of the atrial pacemaker to dobutamine.", "content": "The action of dobutamine, (+/-)-4- [2- [[3-(p-hydroxyphenyl)-1-methylpropyl]amino]ethyl] pyrocatechol hydrochloride was studied on the pacemaker of the isolated rat atria. The dose-chronotropic response curve showed a typical bell-dome shape of the sympathomimetic amines. Reserpinization of the animals did not change the curve of the agonist. Cocaine (6.7 microgram/ml) induced a decrease of the sensitivity of the rat atria pacemaker for dobutamine (p less than 0.001). Propranolol (3 X 10(-8) and 10(-7) M) provoked a shift to the right of the dose-response curve for dobutamine. Also, the last concentration of the antagonist depressed the maxima (p less than 0.01). Phentolamine failed to prove a possible alpha-adrenergic action of the drug on the pacemaker. The response to dobutamine was not affected when monoaminoxidase was inhibited by pretreatment with pargyline, or when catechol-O-methyltransferase was inhibited by exposure to U-0521 (3,4 dihydroxy-alpha-methylpropiophenone). These results indicate that dobutamine: a) is a beta-adrenergic agent, b) is not a good substrate of MAO, c) is a direct-acting sympathomimetic amine.", "contents": "Response of the atrial pacemaker to dobutamine. The action of dobutamine, (+/-)-4- [2- [[3-(p-hydroxyphenyl)-1-methylpropyl]amino]ethyl] pyrocatechol hydrochloride was studied on the pacemaker of the isolated rat atria. The dose-chronotropic response curve showed a typical bell-dome shape of the sympathomimetic amines. Reserpinization of the animals did not change the curve of the agonist. Cocaine (6.7 microgram/ml) induced a decrease of the sensitivity of the rat atria pacemaker for dobutamine (p less than 0.001). Propranolol (3 X 10(-8) and 10(-7) M) provoked a shift to the right of the dose-response curve for dobutamine. Also, the last concentration of the antagonist depressed the maxima (p less than 0.01). Phentolamine failed to prove a possible alpha-adrenergic action of the drug on the pacemaker. The response to dobutamine was not affected when monoaminoxidase was inhibited by pretreatment with pargyline, or when catechol-O-methyltransferase was inhibited by exposure to U-0521 (3,4 dihydroxy-alpha-methylpropiophenone). These results indicate that dobutamine: a) is a beta-adrenergic agent, b) is not a good substrate of MAO, c) is a direct-acting sympathomimetic amine."}
{"id": "PMID:210634", "title": "Serum triglycerides and cholesterol and serum high-density lipoprotein cholesterol in highly physically active men.", "content": "The influence of extensive physical activity upon plasma lipids, in particular HDL cholesterol, was investigated. The material consisted of 23 regularly training men (mean age 44 years, average exercise 83 km running or skiing weekly), 15 healthy men (mean age 47 years), 10 young men (mean age 22 years), 12 healthy women (mean age 32 years) and 18 hyperlipidaemic patients. The exercise increased serum HDL cholesterol and FFA concentrations and decreased triglyceride levels significantly, but had no significant effect upon serum cholesterol concentration. There was a positive correlation between the amount of weekly exercise in km and plasma HDL cholesterol concentration. Exercising more than 70 km/week increased plasma HDL concentration clearly above the normal level. The advantages of an increase in plasma HDL cholesterol are discussed.", "contents": "Serum triglycerides and cholesterol and serum high-density lipoprotein cholesterol in highly physically active men. The influence of extensive physical activity upon plasma lipids, in particular HDL cholesterol, was investigated. The material consisted of 23 regularly training men (mean age 44 years, average exercise 83 km running or skiing weekly), 15 healthy men (mean age 47 years), 10 young men (mean age 22 years), 12 healthy women (mean age 32 years) and 18 hyperlipidaemic patients. The exercise increased serum HDL cholesterol and FFA concentrations and decreased triglyceride levels significantly, but had no significant effect upon serum cholesterol concentration. There was a positive correlation between the amount of weekly exercise in km and plasma HDL cholesterol concentration. Exercising more than 70 km/week increased plasma HDL concentration clearly above the normal level. The advantages of an increase in plasma HDL cholesterol are discussed."}
{"id": "PMID:210635", "title": "Glucagon effects on plasma cyclic AMP and other reactants in normals and low insulin responders.", "content": "The metabolic response to i.v. glucagon was evaluated in 11 normal individuals and 8 healthy low insulin responders. Elevations of plasma cyclic AMP and blood glucose were similar in both groups. Accordingly, no indications were seen of differing hepatic responsiveness to glucagon. In contrast, the groups differed in the course of plasma glycerol during the test.", "contents": "Glucagon effects on plasma cyclic AMP and other reactants in normals and low insulin responders. The metabolic response to i.v. glucagon was evaluated in 11 normal individuals and 8 healthy low insulin responders. Elevations of plasma cyclic AMP and blood glucose were similar in both groups. Accordingly, no indications were seen of differing hepatic responsiveness to glucagon. In contrast, the groups differed in the course of plasma glycerol during the test."}
{"id": "PMID:210638", "title": "A proposed bioanthropological approach linking ritual and opiate addiction.", "content": "This paper presents preliminary conjectures about possible neurobiological relationships among seemingly disparate phenomena: religious rituals, native curing therapies, and the pharmacodynamic, psychological, and sociocultural components of opiate addiction. Central to the discussion is an analysis of the function of opiate receptors, the endogenous neurochemical that binds to opiate receptors, and the impact of exogenous opiates on human behavior. Throughout the paper a synthetic but admittedly speculative approach is employed.", "contents": "A proposed bioanthropological approach linking ritual and opiate addiction. This paper presents preliminary conjectures about possible neurobiological relationships among seemingly disparate phenomena: religious rituals, native curing therapies, and the pharmacodynamic, psychological, and sociocultural components of opiate addiction. Central to the discussion is an analysis of the function of opiate receptors, the endogenous neurochemical that binds to opiate receptors, and the impact of exogenous opiates on human behavior. Throughout the paper a synthetic but admittedly speculative approach is employed."}
{"id": "PMID:210640", "title": "The localization of a histamine H2-receptor adenylate cyclase system in canine parietal cells and its inhibition by prostaglandins.", "content": "A method is described for the preparation of parietal cell-enriched suspensions from dog gastric mucosa. Histamine and E type prostaglandins produce an elevation of cyclic AMP concentration in mixed cell preparations. Parietal cell-rich fractions respond to histamine but only weakly to prostaglandins whilst in fractions virtually free from parietal cells the converse is observed. Prostaglandins which are good antisecretory agents, PGE1, PGE2 and 16,16 dimethyl PGE2 are potent inhibitors of the histamine elevations of cyclic AMP in parietal cell-rich fractions, whilst PFG2alpha shows 1% of their potency. The experiments described support the view that histamine stimulates gastric acid secretion by excitation of an H2-receptor adenylate cyclase system in the plasma membrane of the parietal cell and that acid secretory inhibition by prostaglandins is a result of inhibition of that system.", "contents": "The localization of a histamine H2-receptor adenylate cyclase system in canine parietal cells and its inhibition by prostaglandins. A method is described for the preparation of parietal cell-enriched suspensions from dog gastric mucosa. Histamine and E type prostaglandins produce an elevation of cyclic AMP concentration in mixed cell preparations. Parietal cell-rich fractions respond to histamine but only weakly to prostaglandins whilst in fractions virtually free from parietal cells the converse is observed. Prostaglandins which are good antisecretory agents, PGE1, PGE2 and 16,16 dimethyl PGE2 are potent inhibitors of the histamine elevations of cyclic AMP in parietal cell-rich fractions, whilst PFG2alpha shows 1% of their potency. The experiments described support the view that histamine stimulates gastric acid secretion by excitation of an H2-receptor adenylate cyclase system in the plasma membrane of the parietal cell and that acid secretory inhibition by prostaglandins is a result of inhibition of that system."}
{"id": "PMID:210644", "title": "Radiologic assessment of pituitary microadenomas.", "content": "Radiographs of 146 patients who had a pituitary adenoma removed by the transsphenoidal approach were reviewed. The area and volume of the sella were measured in all the patients. In 73 patients the sella had a normal size and appearance as shown on routine lateral and frontal radiographs. However, thin-section tomograms of the sella in these patients demonstrated findings indicative of an intrasellar mass in all but three instances. The diagnosis of pituitary microadenoma (adenoma less than 1.5 cm in diameter) may, therefore, be missed if only plain skull radiographs are used to assess the sella. No correlation could be shown between the location of the sellar changes seen using thin-section tomography and the histologic type of pituitary adenoma.", "contents": "Radiologic assessment of pituitary microadenomas. Radiographs of 146 patients who had a pituitary adenoma removed by the transsphenoidal approach were reviewed. The area and volume of the sella were measured in all the patients. In 73 patients the sella had a normal size and appearance as shown on routine lateral and frontal radiographs. However, thin-section tomograms of the sella in these patients demonstrated findings indicative of an intrasellar mass in all but three instances. The diagnosis of pituitary microadenoma (adenoma less than 1.5 cm in diameter) may, therefore, be missed if only plain skull radiographs are used to assess the sella. No correlation could be shown between the location of the sellar changes seen using thin-section tomography and the histologic type of pituitary adenoma."}
{"id": "PMID:210645", "title": "interactions of ionizing radiation, nitrosamines, sulfonoxyalkanes and antioxidants as they affect carcinogenesis and survival in mice.", "content": "Butylated hydroxytoluene (BHT), pretreatment of 8-wk-old BALB/c mice for 28 days protected against 30-day lethality by X-rays, diethylnitrosamine (DEN), dimethylnitrosamine (DMN) and ethyl methanesulfonate (EMS) but not against methyl methanesulfonate (MMS). In X-ray survivors, neither mean survival nor leukemia incidences were affected by BHT. However, BHT (lifetime), given alone or with DEN (300 MG/KG BW in H2O) or 250 R X-rays, increased irradiated survivors at 18 months but not leukemia or tumor incidences. BHT + DEN treated females had increased survival and a decreased frequency of forestomach squamous carcinomas compared with DEN alone; no differences were seen in males or in pulmonary adenomas. In X-ray + DEN treated females, effect upon survival was additive, but the specific diseases causing this effect were not identified.", "contents": "interactions of ionizing radiation, nitrosamines, sulfonoxyalkanes and antioxidants as they affect carcinogenesis and survival in mice. Butylated hydroxytoluene (BHT), pretreatment of 8-wk-old BALB/c mice for 28 days protected against 30-day lethality by X-rays, diethylnitrosamine (DEN), dimethylnitrosamine (DMN) and ethyl methanesulfonate (EMS) but not against methyl methanesulfonate (MMS). In X-ray survivors, neither mean survival nor leukemia incidences were affected by BHT. However, BHT (lifetime), given alone or with DEN (300 MG/KG BW in H2O) or 250 R X-rays, increased irradiated survivors at 18 months but not leukemia or tumor incidences. BHT + DEN treated females had increased survival and a decreased frequency of forestomach squamous carcinomas compared with DEN alone; no differences were seen in males or in pulmonary adenomas. In X-ray + DEN treated females, effect upon survival was additive, but the specific diseases causing this effect were not identified."}
{"id": "PMID:210646", "title": "Tolyl-specific IgE antibodies in workders with hypersensitivity to toluene diisocyanate.", "content": "Incorporation of a p-tolyl (mono) isocyanate-human serum albumin (TMI-HSA) antigen conjugate into a solid phase radioimmunoassay permitted detection of tolyl-specific IgE antibodies in 3 of 4 workers with clinical hypersensitivity to toluene diisocyanate (TDI). By comparison 19 TDI-exposed, non-sensitized workers had antibody titers similar to those found in normal adults. High titers of tolyl-specific IgE antibodies were not correlated with high levels of total serum IgE. Use of the monofunctional isocyanate in place of TDI in antigen preparation prevented cross-linking of antigen protein, an effect usually associated with TDI, and also assured that tolyl groups were sterically exposed. TMI-HSA antigens may prove beneficial in serological or cutaneous evaluation of TDI-sensitized workers.", "contents": "Tolyl-specific IgE antibodies in workders with hypersensitivity to toluene diisocyanate. Incorporation of a p-tolyl (mono) isocyanate-human serum albumin (TMI-HSA) antigen conjugate into a solid phase radioimmunoassay permitted detection of tolyl-specific IgE antibodies in 3 of 4 workers with clinical hypersensitivity to toluene diisocyanate (TDI). By comparison 19 TDI-exposed, non-sensitized workers had antibody titers similar to those found in normal adults. High titers of tolyl-specific IgE antibodies were not correlated with high levels of total serum IgE. Use of the monofunctional isocyanate in place of TDI in antigen preparation prevented cross-linking of antigen protein, an effect usually associated with TDI, and also assured that tolyl groups were sterically exposed. TMI-HSA antigens may prove beneficial in serological or cutaneous evaluation of TDI-sensitized workers."}
{"id": "PMID:210648", "title": "Prevalence of right ventricular involvement in inferior wall infarction assessed with myocardial imaging with thallium-201 and technetium-99m pyrophosphate.", "content": "To assess the prevalence and clinical relevance of right ventricular involvement in acute inferior wall infarction, 78 consecutive patients with the latter condition were studied with thallium-201 and technethium-99m pyrophosphate myocardial imaging. Right ventricular involvement was determined from superimposition of the 45 degree left anterior oblique thallium-201 and technetium-99m pyrophosphate images. All 78 patients shoed thallium-201 defects. Sixty-four patients had positive pyrophosphate scans, and 24 of these (37.5 percent) showed right ventricular involvement. None of the patients with right ventricular involvement in this consecutive series showed the classic signs of severe right ventricular failure, although subclinicalright ventricular dysfunction may have been present. There was no significant difference in the incidence of cardiogenic shock between the groups with and without right ventricular involvement. It is concluded that right ventricular involvement in acute inferior wall infarction is relatively frequent but not necessarily associated with severe right-sided pump failure. In patients with acute inferior wall infarction and severe pump failure, dual imaging provides a simple nonivasive method of identifying the subgroup of patients with right ventricular involvement who may benefit from volume loading.", "contents": "Prevalence of right ventricular involvement in inferior wall infarction assessed with myocardial imaging with thallium-201 and technetium-99m pyrophosphate. To assess the prevalence and clinical relevance of right ventricular involvement in acute inferior wall infarction, 78 consecutive patients with the latter condition were studied with thallium-201 and technethium-99m pyrophosphate myocardial imaging. Right ventricular involvement was determined from superimposition of the 45 degree left anterior oblique thallium-201 and technetium-99m pyrophosphate images. All 78 patients shoed thallium-201 defects. Sixty-four patients had positive pyrophosphate scans, and 24 of these (37.5 percent) showed right ventricular involvement. None of the patients with right ventricular involvement in this consecutive series showed the classic signs of severe right ventricular failure, although subclinicalright ventricular dysfunction may have been present. There was no significant difference in the incidence of cardiogenic shock between the groups with and without right ventricular involvement. It is concluded that right ventricular involvement in acute inferior wall infarction is relatively frequent but not necessarily associated with severe right-sided pump failure. In patients with acute inferior wall infarction and severe pump failure, dual imaging provides a simple nonivasive method of identifying the subgroup of patients with right ventricular involvement who may benefit from volume loading."}
{"id": "PMID:210649", "title": "Long-term effectiveness of dietary iron and ascorbic acid in the prevention and cure of cadmium toxicity in rats.", "content": "The protective and curative effects of dietary iron and ascorbic acid on chronic (180 days) cadmium toxicity in rats were examined. Growth retardation and anemia were observed in rats fed a diet containing 50 ppm of cadmium for 180 days; during this period the contents of iron in the liver, kidney, spleen, testis, intestine, and tibia decreased and the zinc contents of the liver and kidney increased, but the calcium content of bone did not change. Addition of 400 ppm of iron and 1% of ascorbic acid to the cadmium-containing diet overcame the growth retardation and anemia due to cadmium toxicity and reduced the tissue levels of cadmium; however, it did not restore the zinc contents in the liver, kidney, and bone to normal. Similar effects were observed when these compounds were added to cadmium containing diet for 90 days after feeding the cadmium diet alone for 90 days. The glutamic-pyruvic transminase and glutamic-oxaloacetic transminase activities in the plasma of rats fed the cadmium diet increased significantly and these increases were prevented by supplementing the diet with iron and ascorbic acid. Glucose, urea, and alkaline phosphatase in the plasma and glycogen in the liver were not changed by feeding the cadmium diet for 180 days. These results indicate the long-term effectiveness of supplementing the diet with iron and ascorbic-acid for preventing and curing dietary cadmium toxicity in rats.", "contents": "Long-term effectiveness of dietary iron and ascorbic acid in the prevention and cure of cadmium toxicity in rats. The protective and curative effects of dietary iron and ascorbic acid on chronic (180 days) cadmium toxicity in rats were examined. Growth retardation and anemia were observed in rats fed a diet containing 50 ppm of cadmium for 180 days; during this period the contents of iron in the liver, kidney, spleen, testis, intestine, and tibia decreased and the zinc contents of the liver and kidney increased, but the calcium content of bone did not change. Addition of 400 ppm of iron and 1% of ascorbic acid to the cadmium-containing diet overcame the growth retardation and anemia due to cadmium toxicity and reduced the tissue levels of cadmium; however, it did not restore the zinc contents in the liver, kidney, and bone to normal. Similar effects were observed when these compounds were added to cadmium containing diet for 90 days after feeding the cadmium diet alone for 90 days. The glutamic-pyruvic transminase and glutamic-oxaloacetic transminase activities in the plasma of rats fed the cadmium diet increased significantly and these increases were prevented by supplementing the diet with iron and ascorbic acid. Glucose, urea, and alkaline phosphatase in the plasma and glycogen in the liver were not changed by feeding the cadmium diet for 180 days. These results indicate the long-term effectiveness of supplementing the diet with iron and ascorbic-acid for preventing and curing dietary cadmium toxicity in rats."}
{"id": "PMID:210651", "title": "Increased histidine and histamine content in the brain of chronic uremic rats. Cause of enhanced cerebral cyclic adenosine monophosphate in uremia?", "content": "In rats with experimental chronic renal insufficiency (90% nephrectomy) the histidine content in brain was increased (+ 35%) in spite of normal plasma values and decreased concentrations in the striated muscle (-23%). The finding of a raised histidine level in the brain seems to be a uremia specific disorder, probably cuased by a local disturbance in histidine metabolism. In addition an increase of the histidine decarboxylation product histamine could be observed in the brain of rats with chronic renal insufficiency, as compared to pair-fed controls. This increase was directly related to the severity of azotemia. In the pathogenesis of the histamine alteration the increased histidine content in the brain of uremic rats must be considered, since the specific histidine decarboxylase is not saturated by the normal endogenous level of the amino acid precursor. Probably the increased histamine contributes to the raised cerebral cyclic AMP in the brain of uremic rats.", "contents": "Increased histidine and histamine content in the brain of chronic uremic rats. Cause of enhanced cerebral cyclic adenosine monophosphate in uremia? In rats with experimental chronic renal insufficiency (90% nephrectomy) the histidine content in brain was increased (+ 35%) in spite of normal plasma values and decreased concentrations in the striated muscle (-23%). The finding of a raised histidine level in the brain seems to be a uremia specific disorder, probably cuased by a local disturbance in histidine metabolism. In addition an increase of the histidine decarboxylation product histamine could be observed in the brain of rats with chronic renal insufficiency, as compared to pair-fed controls. This increase was directly related to the severity of azotemia. In the pathogenesis of the histamine alteration the increased histidine content in the brain of uremic rats must be considered, since the specific histidine decarboxylase is not saturated by the normal endogenous level of the amino acid precursor. Probably the increased histamine contributes to the raised cerebral cyclic AMP in the brain of uremic rats."}
{"id": "PMID:210652", "title": "Overview and horizons in prevention of some human infectious diseases by vaccination.", "content": "The present measles problem in the United States, an estimated 918,500 cases in 1977, is attributed to the failure of the 14-year vaccination program to immunize enough children to prevent continued circulation of the virus and recurrent outbreaks. A new strategy for rapidly overcoming this problem is recommended. There appears to be no current congenital rubella syndrome problem against which the rubella vaccination program in the United States is directed. However, the continued annual infection of an estimated two million children conceivably could again bring fourth a rubella virus with a greater capacity for producing congenital rubella syndrome, and a modification of the present program is recommended. About 80 to 90% of the annual 60-70 million cases of severe enough to confine the victim to bed influenza are not caused by the influenza viruses. Except for the few thousand additional deaths directly attributed to influenza A virus during the epidemic years, mortality rates for pneumonia, heart diseases, chronic bronchopulmonary diseases, and other former \"high-risk\" conditions have continued to decrease in recent years, and have not risen during the 12-month periods of epidemic years. A re-evaluation of the current influenza vaccination policy is recommended. Prospects for hepatitis B and varicella-zoster vaccines are discussed.", "contents": "Overview and horizons in prevention of some human infectious diseases by vaccination. The present measles problem in the United States, an estimated 918,500 cases in 1977, is attributed to the failure of the 14-year vaccination program to immunize enough children to prevent continued circulation of the virus and recurrent outbreaks. A new strategy for rapidly overcoming this problem is recommended. There appears to be no current congenital rubella syndrome problem against which the rubella vaccination program in the United States is directed. However, the continued annual infection of an estimated two million children conceivably could again bring fourth a rubella virus with a greater capacity for producing congenital rubella syndrome, and a modification of the present program is recommended. About 80 to 90% of the annual 60-70 million cases of severe enough to confine the victim to bed influenza are not caused by the influenza viruses. Except for the few thousand additional deaths directly attributed to influenza A virus during the epidemic years, mortality rates for pneumonia, heart diseases, chronic bronchopulmonary diseases, and other former \"high-risk\" conditions have continued to decrease in recent years, and have not risen during the 12-month periods of epidemic years. A re-evaluation of the current influenza vaccination policy is recommended. Prospects for hepatitis B and varicella-zoster vaccines are discussed."}
{"id": "PMID:210654", "title": "Varicella-zoster virus. Prospects for active immunization.", "content": "A live attenuated varicella-zoster (V-Z) virus vaccine has been developed and tested by Dr. M. Takahashi and his colleagues in Japan. This vaccine appears to prevent varicella and is associated with minimal side effects even in patients at high risk to develop severe varicella. Antibody to V-Z virus appears after V-Z vaccination. This antibody has been detected by a variety of serologic technics, and it has been demonstrated to persist for as long as two years after vaccination. Thus far, V-Z vaccine has not been associated with subsequent zoster, but long-term studies will be required before this possibility can be ruled out.", "contents": "Varicella-zoster virus. Prospects for active immunization. A live attenuated varicella-zoster (V-Z) virus vaccine has been developed and tested by Dr. M. Takahashi and his colleagues in Japan. This vaccine appears to prevent varicella and is associated with minimal side effects even in patients at high risk to develop severe varicella. Antibody to V-Z virus appears after V-Z vaccination. This antibody has been detected by a variety of serologic technics, and it has been demonstrated to persist for as long as two years after vaccination. Thus far, V-Z vaccine has not been associated with subsequent zoster, but long-term studies will be required before this possibility can be ruled out."}
{"id": "PMID:210655", "title": "Kleine-Levin syndrome associated with fire setting.", "content": "Kleine-Levin syndrome is characterized by periodic hypersomnia associated with megaphagia and striking behavioral and psychiatric symptoms; it occurs primarily in adolescent boys. We treated a 17-year-old boy who had typical recurring somnolent episodes. His bizarre behavior included fire setting and stealing, both of which may have represented compulsions. His EEG during a sleepy episode was diffusely abnormal with generalized slowing of background activity; as he awoke and improved clinically, his EEG returned to normal. Between episodes, his EEG was normal. The relationship between Kleine-Levin syndrome and other sleep disorders is discussed. The neurochemistry and neurocircuitry that may provide the requisite substrate for this complex and fascinating neuropsychiatric disorder are briefly reviewed.", "contents": "Kleine-Levin syndrome associated with fire setting. Kleine-Levin syndrome is characterized by periodic hypersomnia associated with megaphagia and striking behavioral and psychiatric symptoms; it occurs primarily in adolescent boys. We treated a 17-year-old boy who had typical recurring somnolent episodes. His bizarre behavior included fire setting and stealing, both of which may have represented compulsions. His EEG during a sleepy episode was diffusely abnormal with generalized slowing of background activity; as he awoke and improved clinically, his EEG returned to normal. Between episodes, his EEG was normal. The relationship between Kleine-Levin syndrome and other sleep disorders is discussed. The neurochemistry and neurocircuitry that may provide the requisite substrate for this complex and fascinating neuropsychiatric disorder are briefly reviewed."}
{"id": "PMID:210656", "title": "Comparison of human rotavirus disease in tropical and temperate settings.", "content": "Human rotaviruses (HRV) are a common cause of acute nonbacterial gastroenteritis in pediatric patients. A prospective study of HRV disease in a temperate (Dallas) and a tropical (San Jose, Costa Rica) setting demonstrated differences in seasonal distribution. In both locales, HRV accounted for 50% to 60% of acute nonbacterial gastroenteritis episodes from December through February; this period corresponded to the cooler months of winter in Dallas and to the dry season in San Jose. During the rest of the observation year, the virus was not recovered from any Dallas patients, but was found in 30% to 40% of Costa Rican patients in every month but May. Signs, symptoms, and laboratory values suggest the small bowel as the major site of pathophysiology; mucosal disruption may occur in some cases.", "contents": "Comparison of human rotavirus disease in tropical and temperate settings. Human rotaviruses (HRV) are a common cause of acute nonbacterial gastroenteritis in pediatric patients. A prospective study of HRV disease in a temperate (Dallas) and a tropical (San Jose, Costa Rica) setting demonstrated differences in seasonal distribution. In both locales, HRV accounted for 50% to 60% of acute nonbacterial gastroenteritis episodes from December through February; this period corresponded to the cooler months of winter in Dallas and to the dry season in San Jose. During the rest of the observation year, the virus was not recovered from any Dallas patients, but was found in 30% to 40% of Costa Rican patients in every month but May. Signs, symptoms, and laboratory values suggest the small bowel as the major site of pathophysiology; mucosal disruption may occur in some cases."}
{"id": "PMID:210657", "title": "Obstructive jaundice caused by hepatocellular carcinoma. Report of three cases.", "content": "A cholestatic syndrome secondary to extrahepatic biliary obstruction as the presenting manifestation of hepatocellular carcinoma is described in three cases. The mechanism is related to the invasion of intrahepatic bile ducts by the carcinoma. The consequent mechanical obstruction is due to either a continuous distally growing tumor cast of the biliary tree, distal migration of a necrotic tumor fragment, or hemobilia. In the cirrhotic patient with a predisposition for the development of liver cancer, the physician should be aware of the presentation with obstructive jaundice as a mechanical complication of hepatocellular carcinoma.", "contents": "Obstructive jaundice caused by hepatocellular carcinoma. Report of three cases. A cholestatic syndrome secondary to extrahepatic biliary obstruction as the presenting manifestation of hepatocellular carcinoma is described in three cases. The mechanism is related to the invasion of intrahepatic bile ducts by the carcinoma. The consequent mechanical obstruction is due to either a continuous distally growing tumor cast of the biliary tree, distal migration of a necrotic tumor fragment, or hemobilia. In the cirrhotic patient with a predisposition for the development of liver cancer, the physician should be aware of the presentation with obstructive jaundice as a mechanical complication of hepatocellular carcinoma."}
{"id": "PMID:210658", "title": "Calcified mucinous adenocarcinoma of the stomach.", "content": "Two cases of unusual mucinous adenocarcinomas of the stomach with calcification are reported. One of the cases demonstrated hypercalcemia. Endoscopic verification of the calcifications was confirmed. This report represents the 49th and 50th reported cases in the world's literature.", "contents": "Calcified mucinous adenocarcinoma of the stomach. Two cases of unusual mucinous adenocarcinomas of the stomach with calcification are reported. One of the cases demonstrated hypercalcemia. Endoscopic verification of the calcifications was confirmed. This report represents the 49th and 50th reported cases in the world's literature."}
{"id": "PMID:210659", "title": "Clustering of different subtypes of hepatitis B surface antigen in families of patients with chronic liver diseases.", "content": "Clustering of hepatitis B surface antigen (HBsAg) with both subtypes adr and adw in three families of patients with chronic liver diseases or hepatocellular carcinoma was demonstrated in Taiwan where adw is the main subtype. The subtype in the children was similar to that in their mothers, suggesting maternal transmission. In all the family units clustered with different subtypes, the same pattern occurred, invariably with fathers carrying HBsAg/adr and the children carrying HBsAg/adw. The subtype difference clearly rules out the transmission of hepatitis B virus (HBV) from father. Horizontal infection with the locally dominant adw-subtyped HBV in the children of fathers carrying HBsAg/adr explains the discrepancy of the subtypes in these families. Clustering of two HBsAg-positive brothers with hepatocellular carcinoma in one of the families was found. That both adr-subtyped and adw-subtyped HBV are capable of inducing chronic active hepatitis in another family suggests that host factors are probably more important in determining the clinical course of HBV infection.", "contents": "Clustering of different subtypes of hepatitis B surface antigen in families of patients with chronic liver diseases. Clustering of hepatitis B surface antigen (HBsAg) with both subtypes adr and adw in three families of patients with chronic liver diseases or hepatocellular carcinoma was demonstrated in Taiwan where adw is the main subtype. The subtype in the children was similar to that in their mothers, suggesting maternal transmission. In all the family units clustered with different subtypes, the same pattern occurred, invariably with fathers carrying HBsAg/adr and the children carrying HBsAg/adw. The subtype difference clearly rules out the transmission of hepatitis B virus (HBV) from father. Horizontal infection with the locally dominant adw-subtyped HBV in the children of fathers carrying HBsAg/adr explains the discrepancy of the subtypes in these families. Clustering of two HBsAg-positive brothers with hepatocellular carcinoma in one of the families was found. That both adr-subtyped and adw-subtyped HBV are capable of inducing chronic active hepatitis in another family suggests that host factors are probably more important in determining the clinical course of HBV infection."}
{"id": "PMID:210660", "title": "Travelers' diarrhea among United States Marines in South Korea.", "content": "A battalion of United States Marines traveling to South Korea in the spring of 1976 was studied to determine the incidence and etiology of gastroenteritis. During the three weeks they visited South Korea, 21% of 694 marines developed diarrhea. Stool and serum specimens collected before, during, and after their stay were examined for evidence of infection with Salmonella, Shigella, and Vibrio species, enterotoxigenic and invasive Escherichia coli, reovirus-like agent (RVLA), and intestinal ova and parasites. Infections with these agents were uncommon; 91% of 44 closely studied cases of gastorenteritis were unexplained. Five per cent of 169 marines had serologic evidence of recent infection with RVLA, and 3% of 273 marines had serologic evidence of infection with heat-labile enterotoxin producing E. coli over an eight-week period. However, infections with these agents were not associated with most cases of diarrhea in South Korea. It is concluded that infectious agents previously thought responsible for travelers' diarrhea were not responsible for gastroenteritis among United States Marines arriving in a temperate climate.", "contents": "Travelers' diarrhea among United States Marines in South Korea. A battalion of United States Marines traveling to South Korea in the spring of 1976 was studied to determine the incidence and etiology of gastroenteritis. During the three weeks they visited South Korea, 21% of 694 marines developed diarrhea. Stool and serum specimens collected before, during, and after their stay were examined for evidence of infection with Salmonella, Shigella, and Vibrio species, enterotoxigenic and invasive Escherichia coli, reovirus-like agent (RVLA), and intestinal ova and parasites. Infections with these agents were uncommon; 91% of 44 closely studied cases of gastorenteritis were unexplained. Five per cent of 169 marines had serologic evidence of recent infection with RVLA, and 3% of 273 marines had serologic evidence of infection with heat-labile enterotoxin producing E. coli over an eight-week period. However, infections with these agents were not associated with most cases of diarrhea in South Korea. It is concluded that infectious agents previously thought responsible for travelers' diarrhea were not responsible for gastroenteritis among United States Marines arriving in a temperate climate."}
{"id": "PMID:210662", "title": "Effect of cyclic nucleotides on mitogen. Responsiveness of lymphocytes from patients undergoing dialysis.", "content": "Lymphocytes from 10 asymptomatic patients undergoing hemodialysis and from eight control subjects were repeatedly cultured with exposure to various concentrations of cyclic nucleotides and theophylline in addition to mitogen. The blastogenic response of the patients' lymphocytes was inhibited by molar concentrations of dibutyryl cyclic AMP which had much less or no inhibitory effected on the response of the control subjects' lymphocytes. This suppressive effect was not potentiated by theophylline. Cyclic GMP enhanced the proliferative response of the patients' lymphocytes as well as that of the controls. In contrast to absolute counts per minute per culture, the suppression by dibutyryl cyclic AMP of mitogen-induced blastogenesis noted in this study clearly separated the in vitro behavior of the patients' lymphocytes from  that of the controls' lymphocytes and may serve as a useful marker of cellular dysfunction in such patients.", "contents": "Effect of cyclic nucleotides on mitogen. Responsiveness of lymphocytes from patients undergoing dialysis. Lymphocytes from 10 asymptomatic patients undergoing hemodialysis and from eight control subjects were repeatedly cultured with exposure to various concentrations of cyclic nucleotides and theophylline in addition to mitogen. The blastogenic response of the patients' lymphocytes was inhibited by molar concentrations of dibutyryl cyclic AMP which had much less or no inhibitory effected on the response of the control subjects' lymphocytes. This suppressive effect was not potentiated by theophylline. Cyclic GMP enhanced the proliferative response of the patients' lymphocytes as well as that of the controls. In contrast to absolute counts per minute per culture, the suppression by dibutyryl cyclic AMP of mitogen-induced blastogenesis noted in this study clearly separated the in vitro behavior of the patients' lymphocytes from  that of the controls' lymphocytes and may serve as a useful marker of cellular dysfunction in such patients."}
{"id": "PMID:210664", "title": "Continuous flow plasma exchange in the treatment of homozygous familial hypercholesterolemia.", "content": "We report the clinical and laboratory effects of continuous-flow plasma exchange in two patients suffering from homozygous familial hypercholesterolemia. In one (Case 1) plasmapheresis was performed at fortnightly intervals over a period of 18 months; in the other (Case 2) the necessity for surgical relief of an associated supravalvular aortic stenosis resulted in premature termination of the trial. The plasma cholesterol levels in both patients fell by 35 per cent from the mean before study in the course of treatment. In Case 1 this was associated with marked regression of the patient's xanthomas, disappearance of the S-T segment depression seen on effort electrocardiograms obtained prior to the introduction of plasmapheresis, possible widening of the stenosis present at the origin of the left anterior descending coronary artery, and a marked increase in exercise tolerance and diminished frequency of anginal attacks. Cessation of cholestyramine and clofibrate administration during this study did not in any way reverse the reduction of plasma cholesterol achieved by means of plasmapheresis combined with drug therapy. We conclude that plasmapheresis has a role to play in the management of patients with homozygous familial hypercholesterolemia.", "contents": "Continuous flow plasma exchange in the treatment of homozygous familial hypercholesterolemia. We report the clinical and laboratory effects of continuous-flow plasma exchange in two patients suffering from homozygous familial hypercholesterolemia. In one (Case 1) plasmapheresis was performed at fortnightly intervals over a period of 18 months; in the other (Case 2) the necessity for surgical relief of an associated supravalvular aortic stenosis resulted in premature termination of the trial. The plasma cholesterol levels in both patients fell by 35 per cent from the mean before study in the course of treatment. In Case 1 this was associated with marked regression of the patient's xanthomas, disappearance of the S-T segment depression seen on effort electrocardiograms obtained prior to the introduction of plasmapheresis, possible widening of the stenosis present at the origin of the left anterior descending coronary artery, and a marked increase in exercise tolerance and diminished frequency of anginal attacks. Cessation of cholestyramine and clofibrate administration during this study did not in any way reverse the reduction of plasma cholesterol achieved by means of plasmapheresis combined with drug therapy. We conclude that plasmapheresis has a role to play in the management of patients with homozygous familial hypercholesterolemia."}
{"id": "PMID:210665", "title": "Ectopic secretion of chorionic gonadotropin by a lung carcinoma. Pituitary gonadotropin and subunit secretion and prolonged chemotherapeutic remission.", "content": "The ability of tumor markers to improve cancer therapy is not established. We studied a man with a human chorionic gonadotropin (HCG)-secreting large cell carcinoma of the lung and gynecomastia. Preoperatively, levels of HCG (109 ng/ml), its alpha and beta subunits (3.2 and 21 ng/ml, respectively) and plasma estradiol were elevated. Despite apparently complete tumor resection and total resolution of gynecomastia, HCG titers remained elevated (3.3 ng/ml), heralding tumor recurrence three weeks later. Because the pathophysiologic consequences of the ectopic secretion of HCG on pituitary function are not established, we administered 100 microgram of gonadotropin-releasing hormone (LHRH) and observed a markedly delayed increase in pituitary gonadotropins. Early chemotherapy, guided by persistence of HCG, reduced HCG to undetectable levels, restored to normal the response to LHRH and resulted in a distinctly unusual 30-month complete remission. Use of HCG as a tumor marker levels is more sensitive than the symptom of gynecomastia and may permit detection of small, potentially curable tumor foci.", "contents": "Ectopic secretion of chorionic gonadotropin by a lung carcinoma. Pituitary gonadotropin and subunit secretion and prolonged chemotherapeutic remission. The ability of tumor markers to improve cancer therapy is not established. We studied a man with a human chorionic gonadotropin (HCG)-secreting large cell carcinoma of the lung and gynecomastia. Preoperatively, levels of HCG (109 ng/ml), its alpha and beta subunits (3.2 and 21 ng/ml, respectively) and plasma estradiol were elevated. Despite apparently complete tumor resection and total resolution of gynecomastia, HCG titers remained elevated (3.3 ng/ml), heralding tumor recurrence three weeks later. Because the pathophysiologic consequences of the ectopic secretion of HCG on pituitary function are not established, we administered 100 microgram of gonadotropin-releasing hormone (LHRH) and observed a markedly delayed increase in pituitary gonadotropins. Early chemotherapy, guided by persistence of HCG, reduced HCG to undetectable levels, restored to normal the response to LHRH and resulted in a distinctly unusual 30-month complete remission. Use of HCG as a tumor marker levels is more sensitive than the symptom of gynecomastia and may permit detection of small, potentially curable tumor foci."}
{"id": "PMID:210668", "title": "Gonadotropin receptors of human corpus luteum during menstrual cycle and pregnancy.", "content": "Specific high-affinity low-capacity binding of human chorionic gonadotropin (hCG) and lutropin (hLH) was demonstrated in the plasma membrane fractions of human corpora lutea. The number of binding sites for both hormones increased from early to late luteal phase, whereas regressing corpus luteum from proliferative phase did not bind either hormone. On the basis of apparent dissociation constants the affinity of the receptor for hLH is highest during early luteal phase and decreases toward the end of the cycle, which may reflect an increasing insensitivity of the corpus luteum to circulating hLH. By contrast, the affinity of the receptor for hCG is highest in the midluteal phase. There are gonadotropin binding sites in the human corpus luteum also during pregnancy, but they are saturated by endogenous hCG. Evidence for this was obtained by elution of hCG with 0.15M sodium chloride at pH 2.3 from washed plasma membrane fractions of luteal tissue from six to 16 week's gestation. After acid treatment and neutralization these preparations showed specific binding for 125I-labeled hCG, but not for 125I-labeled hLH. Our results demonstrate a shift in the balance of affinity of the gonadotropin receptor from hLH to hCG during the course of luteal phase, and during pregnancy the binding sites appear to be available for hCG only.", "contents": "Gonadotropin receptors of human corpus luteum during menstrual cycle and pregnancy. Specific high-affinity low-capacity binding of human chorionic gonadotropin (hCG) and lutropin (hLH) was demonstrated in the plasma membrane fractions of human corpora lutea. The number of binding sites for both hormones increased from early to late luteal phase, whereas regressing corpus luteum from proliferative phase did not bind either hormone. On the basis of apparent dissociation constants the affinity of the receptor for hLH is highest during early luteal phase and decreases toward the end of the cycle, which may reflect an increasing insensitivity of the corpus luteum to circulating hLH. By contrast, the affinity of the receptor for hCG is highest in the midluteal phase. There are gonadotropin binding sites in the human corpus luteum also during pregnancy, but they are saturated by endogenous hCG. Evidence for this was obtained by elution of hCG with 0.15M sodium chloride at pH 2.3 from washed plasma membrane fractions of luteal tissue from six to 16 week's gestation. After acid treatment and neutralization these preparations showed specific binding for 125I-labeled hCG, but not for 125I-labeled hLH. Our results demonstrate a shift in the balance of affinity of the gonadotropin receptor from hLH to hCG during the course of luteal phase, and during pregnancy the binding sites appear to be available for hCG only."}
{"id": "PMID:210669", "title": "Effect of immunization on the development of latent ganglionic infection in mice challenged intravaginally with herpes simplex virus types 1 and 2.", "content": "Immunization of BALB/c mice with virulent and avirulent strains of HSV-1 resulted in high levels of neutralizing antibody and protected against both the lethal effect of the virus and the development of a latent ganglionic infection when animals were challenged by the intravaginal route. In animals immunized with avirulent strain of HSV-2 and challenged with a high virulent strain of HSV-2, substantial protection against death was observed despite low levels of neutralizing antibody. Nineteen per cent of the survivors, however, developed a latent ganglionic infection. Relatively little protection was observed in mice immunized with HSV-1 and challenged with HSV-2.", "contents": "Effect of immunization on the development of latent ganglionic infection in mice challenged intravaginally with herpes simplex virus types 1 and 2. Immunization of BALB/c mice with virulent and avirulent strains of HSV-1 resulted in high levels of neutralizing antibody and protected against both the lethal effect of the virus and the development of a latent ganglionic infection when animals were challenged by the intravaginal route. In animals immunized with avirulent strain of HSV-2 and challenged with a high virulent strain of HSV-2, substantial protection against death was observed despite low levels of neutralizing antibody. Nineteen per cent of the survivors, however, developed a latent ganglionic infection. Relatively little protection was observed in mice immunized with HSV-1 and challenged with HSV-2."}
{"id": "PMID:210666", "title": "Hepatitis A and B: serologic survey of various population groups.", "content": "Seven population groups were tested by radioimmunoassay for the presence of hepatitis A antibody (anti-HAV), hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Detection of anti-HAV was indicative of past hepatitis A infection and presence of HBsAg or anti-HBs indicated past hepatitis B infection. The results of tests of 680 serum specimens from the seven groups were as follows: (1) of 100 newly admitted children to Willowbrook where hepatitis A and B were hyperendemic, 32% had anti-HAV and 4% had anti-HAV and 4% had HBsAg (1%) plus anti-HBs (3%); (2) of 100 Willowbrook residents who lived in the institution about three or more years, 97% had anti-HAV and 90% had HBsAg (32%) plus anti-HBs (58%); (3) of 100 new Willowbrook employees, 50% had anti-HAV and 13% had anti-HBs; (4) of 100 Willowbrook employees who worked in the institution more than three years, 75% had anti-HAV and 30% had HBsAg (3%) plus anti-HBs (27%); (5) of 80 house staff physicians, 27.5% had anti-HAV and 10% had anti-HBs; (6) of 100 student 34% had anti-HAV and 6% had anti-HBs; and (7) of 100 suburban teenagers 4% had anti-HAV and 5% had anti-HBs. This study confirmed the variability of the prevalence of hepatitis A and B markers among different population groups and the effect of socioeconomic status and environmental factors on the incidence of past infection caused by hepatitis A and B viruses.", "contents": "Hepatitis A and B: serologic survey of various population groups. Seven population groups were tested by radioimmunoassay for the presence of hepatitis A antibody (anti-HAV), hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Detection of anti-HAV was indicative of past hepatitis A infection and presence of HBsAg or anti-HBs indicated past hepatitis B infection. The results of tests of 680 serum specimens from the seven groups were as follows: (1) of 100 newly admitted children to Willowbrook where hepatitis A and B were hyperendemic, 32% had anti-HAV and 4% had anti-HAV and 4% had HBsAg (1%) plus anti-HBs (3%); (2) of 100 Willowbrook residents who lived in the institution about three or more years, 97% had anti-HAV and 90% had HBsAg (32%) plus anti-HBs (58%); (3) of 100 new Willowbrook employees, 50% had anti-HAV and 13% had anti-HBs; (4) of 100 Willowbrook employees who worked in the institution more than three years, 75% had anti-HAV and 30% had HBsAg (3%) plus anti-HBs (27%); (5) of 80 house staff physicians, 27.5% had anti-HAV and 10% had anti-HBs; (6) of 100 student 34% had anti-HAV and 6% had anti-HBs; and (7) of 100 suburban teenagers 4% had anti-HAV and 5% had anti-HBs. This study confirmed the variability of the prevalence of hepatitis A and B markers among different population groups and the effect of socioeconomic status and environmental factors on the incidence of past infection caused by hepatitis A and B viruses."}
{"id": "PMID:210667", "title": "Acute asthma. Part II. The effects of therapy on heart rate and blood pressure.", "content": "This study evaluated cardiovascular effects of epinephrine in the treatment of asthma. Heart rates, systolic and diastolic blood pressures were monitored in 64 patients treated for acute asthma. Treatment regimens included subcutaneous epinephrine in doses of 0.1 to 0.5 mg. Pretreatment heart rates ranged from 64 to 136 beats per minute and systolic and diastolic blood pressures from 80 to 190 and 50 to 108 mm Hg respectively. Epinephrine in all doses and repeated as often as three times did not raise blood pressure or heart rates, and in the highest dose or in patients with pressures in the hypertensive range exerted a hypotensive effect. Adverse cardiovascular effects of epinephrine observed in normal subjects are significantly modified in acute asthma and its use should be considered in light of these findings.", "contents": "Acute asthma. Part II. The effects of therapy on heart rate and blood pressure. This study evaluated cardiovascular effects of epinephrine in the treatment of asthma. Heart rates, systolic and diastolic blood pressures were monitored in 64 patients treated for acute asthma. Treatment regimens included subcutaneous epinephrine in doses of 0.1 to 0.5 mg. Pretreatment heart rates ranged from 64 to 136 beats per minute and systolic and diastolic blood pressures from 80 to 190 and 50 to 108 mm Hg respectively. Epinephrine in all doses and repeated as often as three times did not raise blood pressure or heart rates, and in the highest dose or in patients with pressures in the hypertensive range exerted a hypotensive effect. Adverse cardiovascular effects of epinephrine observed in normal subjects are significantly modified in acute asthma and its use should be considered in light of these findings."}
{"id": "PMID:210671", "title": "The treatment of herpetic reinfection with levamisole.", "content": "The effect of levamisole on both clinical disease and virus recovery was studied in rabbits that were first infected with herpes simplex virus in one eye and then reinfected 14 days later by inoculation of the second eye. Reinfected rabbits treated with levamisole before reinfection developed significantly milder and smaller lesions than untreated controls. Virus recovery from the corneas was also less in the levamisole-treated animals than in the untreated controls.", "contents": "The treatment of herpetic reinfection with levamisole. The effect of levamisole on both clinical disease and virus recovery was studied in rabbits that were first infected with herpes simplex virus in one eye and then reinfected 14 days later by inoculation of the second eye. Reinfected rabbits treated with levamisole before reinfection developed significantly milder and smaller lesions than untreated controls. Virus recovery from the corneas was also less in the levamisole-treated animals than in the untreated controls."}
{"id": "PMID:210672", "title": "Mechanisms of platelet adhesion to the basal lamina.", "content": "The human glomerular basal lamina (HGBL) is composed of collagenous and noncollagenous glycoproteins. We assessed the role played by each costituent in platelet-basal-lamina interaction by selective cleavage and removal of each component by clostridial collagenase or by pepsin. When noncollagenous proteins are removed from HGBL, human platelets exhibit littel reactivity toward the residual collagen framework of the isolated basal lamina. With the noncollagen matrix of basal lamina, after removal of the bulk of the collagen, platelet adhesion and spreading proceed normally in the presence of divalent cations, similar to what occurs on intact basal lamina. No platelet degranulation or aggregation is observed. The results indicate that the basal lamina collagen, even in its native packing arrangement, lacks affinity for platelet adhesion and is incapable of triggering platelet release reactions. Platelet adhesion and spreading on the basal lamina appears to depend primarily on the presence of the noncollagen components and to require divalent cations. The data suggest the presence on platelets of receptors for basal lamina distinct from those for interstitial collagens. These receptors activate a unique modulation of platelet behavior, ie, adhesion and spreading without degranulation. A difference in biologic function of the basal lamina and interstitial collagens is apparent in these experiments.", "contents": "Mechanisms of platelet adhesion to the basal lamina. The human glomerular basal lamina (HGBL) is composed of collagenous and noncollagenous glycoproteins. We assessed the role played by each costituent in platelet-basal-lamina interaction by selective cleavage and removal of each component by clostridial collagenase or by pepsin. When noncollagenous proteins are removed from HGBL, human platelets exhibit littel reactivity toward the residual collagen framework of the isolated basal lamina. With the noncollagen matrix of basal lamina, after removal of the bulk of the collagen, platelet adhesion and spreading proceed normally in the presence of divalent cations, similar to what occurs on intact basal lamina. No platelet degranulation or aggregation is observed. The results indicate that the basal lamina collagen, even in its native packing arrangement, lacks affinity for platelet adhesion and is incapable of triggering platelet release reactions. Platelet adhesion and spreading on the basal lamina appears to depend primarily on the presence of the noncollagen components and to require divalent cations. The data suggest the presence on platelets of receptors for basal lamina distinct from those for interstitial collagens. These receptors activate a unique modulation of platelet behavior, ie, adhesion and spreading without degranulation. A difference in biologic function of the basal lamina and interstitial collagens is apparent in these experiments."}
{"id": "PMID:210673", "title": "Actions of peptides isolated from amphibian skin on pancreatic acinar cells.", "content": "In dispersed acinar cells prepared from guinea pig pancreas, peptides isolated from amphibian skin (caerulein, bombesin, litorin, and physalaemin) as well as eledoisin, a peptide isolated from the posterior salivary gland of a Mediterranean octopod, increased outflux of 45Ca, release of bound 45Ca, accumulation of cyclic GMP, and release of amylase. In addition, bombesin, litorin, physalaemin, and eledoisin each increased the initial uptake of 45Ca by dispersed acinar cells, whereas C-terminal octapeptide of porcine cholecystokinin (CCK-OP) and carbamylcholine did not increase the initial uptake of 45Ca but, rather, abolished the increase caused by the other agents. None of the actions of these amphibian peptides was altered by concentrations of atropine sufficient to abolish the effects of muscarinic cholinergic agents. None of the amphibian peptides altered cellular cyclic AMP or the increase caused by secretin or porcine vasoactive intestinal peptide (VIP). Acinar cells preincubated with 45Ca plus bombesin showed the same rate of release of 45Ca as did control cells and this rate was not altered by adding bombesin but was increased fivefold by adding CCK-OP. In terms of their chemical structures as well as the potency and efficacy with which they alter acinar cell function, the amphibian peptides plus CCK-OP can be grouped into three pairs: caerulein with CCK-OP, bombesin with litorin, and physalaemin with eledoisin.", "contents": "Actions of peptides isolated from amphibian skin on pancreatic acinar cells. In dispersed acinar cells prepared from guinea pig pancreas, peptides isolated from amphibian skin (caerulein, bombesin, litorin, and physalaemin) as well as eledoisin, a peptide isolated from the posterior salivary gland of a Mediterranean octopod, increased outflux of 45Ca, release of bound 45Ca, accumulation of cyclic GMP, and release of amylase. In addition, bombesin, litorin, physalaemin, and eledoisin each increased the initial uptake of 45Ca by dispersed acinar cells, whereas C-terminal octapeptide of porcine cholecystokinin (CCK-OP) and carbamylcholine did not increase the initial uptake of 45Ca but, rather, abolished the increase caused by the other agents. None of the actions of these amphibian peptides was altered by concentrations of atropine sufficient to abolish the effects of muscarinic cholinergic agents. None of the amphibian peptides altered cellular cyclic AMP or the increase caused by secretin or porcine vasoactive intestinal peptide (VIP). Acinar cells preincubated with 45Ca plus bombesin showed the same rate of release of 45Ca as did control cells and this rate was not altered by adding bombesin but was increased fivefold by adding CCK-OP. In terms of their chemical structures as well as the potency and efficacy with which they alter acinar cell function, the amphibian peptides plus CCK-OP can be grouped into three pairs: caerulein with CCK-OP, bombesin with litorin, and physalaemin with eledoisin."}
{"id": "PMID:210675", "title": "Action of PMSG and asialo-PMSG on rat Leydig and granulosa cells.", "content": "Highly purified pregnant mares serum gonadotropin (PMSG) was nearly as potent as ovine luteinizing hormone (LH) and human follicle stimulating hormone (hFSH) when bioassayed in vitro in systems known to respond primarily to LH or FSH. An analogue of human chorionic gonadotropin treated with neuraminidase, galactosidase, beta-N-acetylglucosaminidase, and mannosidase (hCG) inhibited the stimulatory effects of hCG, LH, and PMGS on cAMP accumulation in rat Leydig cells but did not inhibit the stimulatory effects of FSH or PMSG on cAMP accumulation in ovarian granulosa cells obtained from immature rats fed diethylstillbestrol. Thus PMSG appeared to form functional complexes with both LH and FSH receptors and may be unique among mammalian gonadotropins. Treatment of PMGS with neuraminidase increased its potency nearly tenfold in vitro apparently by increasing its affinity for both LH and FSH receptors. Although the kinetics of PMSG binding were not investigated with radiolabeled materials, indirect functional binding studies are described that suggest that hCG more rapidly forms stable hormone-receptor complexes than PMSG, asialo-PMSG, FSH, and LH when all hormones are incubated under the same conditions.", "contents": "Action of PMSG and asialo-PMSG on rat Leydig and granulosa cells. Highly purified pregnant mares serum gonadotropin (PMSG) was nearly as potent as ovine luteinizing hormone (LH) and human follicle stimulating hormone (hFSH) when bioassayed in vitro in systems known to respond primarily to LH or FSH. An analogue of human chorionic gonadotropin treated with neuraminidase, galactosidase, beta-N-acetylglucosaminidase, and mannosidase (hCG) inhibited the stimulatory effects of hCG, LH, and PMGS on cAMP accumulation in rat Leydig cells but did not inhibit the stimulatory effects of FSH or PMSG on cAMP accumulation in ovarian granulosa cells obtained from immature rats fed diethylstillbestrol. Thus PMSG appeared to form functional complexes with both LH and FSH receptors and may be unique among mammalian gonadotropins. Treatment of PMGS with neuraminidase increased its potency nearly tenfold in vitro apparently by increasing its affinity for both LH and FSH receptors. Although the kinetics of PMSG binding were not investigated with radiolabeled materials, indirect functional binding studies are described that suggest that hCG more rapidly forms stable hormone-receptor complexes than PMSG, asialo-PMSG, FSH, and LH when all hormones are incubated under the same conditions."}
{"id": "PMID:210676", "title": "GnRH membrane binding: identification, specificity, and quantification in nonpituitary tissues.", "content": "Utilizing biologically active 125I-labeled gonadotropin-releasing hormone (125I-GnRH), specific binding with two affinites [KA (high) = 3.2 x 10(8) M-1, KA (low) = 10(5) M-1] were identified in membrane preparations derived from the 10,800 x g pellet of rat pituitary. GnRH-specific low affinity sites (KA - 10(5) M-1) were identified in liver, spleen, renal cortex, lung, testis, ovary, and cardiac muscle. Hypothalamic tissue demonstrated both high- and low-affinity binding. When 125I-GnRH was bound and dissociated, the labeled GnRH retained fully ability to rebind to fresh membrane preparations. That is, binding was not associated with loss of biological activity of GnRH. However, when unbound 125I-GnRH was exposed to the membrane fraction of liver, almost all receptor binding activity disappeared. The presence of low-affinity binding sites in peripheral tissues raises several possibilities: 1) they act as a simple reservoir mediating metabolic clearance of GnRH; 2) they represent enzyme binding sites involved in degradation of GnRH; 3) they mediate peripheral actions of GnRH; or 4) they are simply a cellular membrane constituent unrelated to target actions of GnRH.", "contents": "GnRH membrane binding: identification, specificity, and quantification in nonpituitary tissues. Utilizing biologically active 125I-labeled gonadotropin-releasing hormone (125I-GnRH), specific binding with two affinites [KA (high) = 3.2 x 10(8) M-1, KA (low) = 10(5) M-1] were identified in membrane preparations derived from the 10,800 x g pellet of rat pituitary. GnRH-specific low affinity sites (KA - 10(5) M-1) were identified in liver, spleen, renal cortex, lung, testis, ovary, and cardiac muscle. Hypothalamic tissue demonstrated both high- and low-affinity binding. When 125I-GnRH was bound and dissociated, the labeled GnRH retained fully ability to rebind to fresh membrane preparations. That is, binding was not associated with loss of biological activity of GnRH. However, when unbound 125I-GnRH was exposed to the membrane fraction of liver, almost all receptor binding activity disappeared. The presence of low-affinity binding sites in peripheral tissues raises several possibilities: 1) they act as a simple reservoir mediating metabolic clearance of GnRH; 2) they represent enzyme binding sites involved in degradation of GnRH; 3) they mediate peripheral actions of GnRH; or 4) they are simply a cellular membrane constituent unrelated to target actions of GnRH."}
{"id": "PMID:210678", "title": "Adrenergic vasoconstriction of the goat middle cerebral artery.", "content": "The effects of field electrical stimulation on the contractile response of the isolated middle cerebral artery of the goat were evaluated before and after the use of experimental procedures designed to test the adrenergic component involved. Supramaximal stimuli produced frequency-dependent increases in tension. This response was significantly reduced by phentolamine (10(-6) M), tetrodotoxin (3 X 10(-6) M), and bretylium (5 X 10(-5) M), but not by cocaine (10(-6) M). Arterial segments from goats pretreated with reserpine and from goats in which both superior cervical sympathetic ganglia had been removed 12 days prior to the experiment also showed a significant decrease in the contraction elicited by electrical stimulation. The norepinephrine concentration of the arteries of the circle of Willis from control goats was 2.10 microgram per gram of tissue. Reserpine or gangliectomy reduced the catecholamine content to undetectable levels. It is likely that a major part of the contractile response of cerebral arteries to electrical stimulation is due to release of endogenous norepinephrine which in turn activates the alpha-adrenergic receptors.", "contents": "Adrenergic vasoconstriction of the goat middle cerebral artery. The effects of field electrical stimulation on the contractile response of the isolated middle cerebral artery of the goat were evaluated before and after the use of experimental procedures designed to test the adrenergic component involved. Supramaximal stimuli produced frequency-dependent increases in tension. This response was significantly reduced by phentolamine (10(-6) M), tetrodotoxin (3 X 10(-6) M), and bretylium (5 X 10(-5) M), but not by cocaine (10(-6) M). Arterial segments from goats pretreated with reserpine and from goats in which both superior cervical sympathetic ganglia had been removed 12 days prior to the experiment also showed a significant decrease in the contraction elicited by electrical stimulation. The norepinephrine concentration of the arteries of the circle of Willis from control goats was 2.10 microgram per gram of tissue. Reserpine or gangliectomy reduced the catecholamine content to undetectable levels. It is likely that a major part of the contractile response of cerebral arteries to electrical stimulation is due to release of endogenous norepinephrine which in turn activates the alpha-adrenergic receptors."}
{"id": "PMID:210680", "title": "Effects of prostaglandin E2, analogs, fatty acids, and indomethacin on fibrinogen level.", "content": "Dose-response relations in rabbits for 3-h intravenous infusion of prostaglandin E2 (PGE2) and (15S)-15-methyl-1-prostaglandin E2 methyl ester (MePGE2) on plasma fibrinogen and systolic blood pressure were determined and described by regression equations. MePGE2 was 20 times more active than PGE2. Fibrinogen synthetic rate responses to PGE2 and MePGE2 were estimated. Infusion of the PGE2 precursor, arachidonic acid, elevated plasma fibrinogen, but fibrinogen response to 0.5-9 mg/kg arachidonic acid was unrelated to dose and half that given by 3 mg/kg PGE2. Slow infusion of several other fatty acids raised plasma fibrinogen as effectively as arachidonic acid, but prostaglandins D2 and F2alpha had only a slight effect. Infusion of 30 times the indomethacin dose that blocks platelet prostaglandin synthetase did not alter the plasma fibrinogen response to arachidonic acid. Indomethacin did not inhibit plasma fibrinogen elevations following ACTH or endotoxin infusion, or subcutaneous turpentine injection. Intravenous infusion of two cyclic ether prostaglandin endoperoxide analogs, (15S)-hydroxy-9alpha, 11alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid, and (15S)-hydroxy-11alpha, 9alpha(epoxymethano) prosta-5Z, 13E-dienoic acid, failed to increase plasma fibrinogen.", "contents": "Effects of prostaglandin E2, analogs, fatty acids, and indomethacin on fibrinogen level. Dose-response relations in rabbits for 3-h intravenous infusion of prostaglandin E2 (PGE2) and (15S)-15-methyl-1-prostaglandin E2 methyl ester (MePGE2) on plasma fibrinogen and systolic blood pressure were determined and described by regression equations. MePGE2 was 20 times more active than PGE2. Fibrinogen synthetic rate responses to PGE2 and MePGE2 were estimated. Infusion of the PGE2 precursor, arachidonic acid, elevated plasma fibrinogen, but fibrinogen response to 0.5-9 mg/kg arachidonic acid was unrelated to dose and half that given by 3 mg/kg PGE2. Slow infusion of several other fatty acids raised plasma fibrinogen as effectively as arachidonic acid, but prostaglandins D2 and F2alpha had only a slight effect. Infusion of 30 times the indomethacin dose that blocks platelet prostaglandin synthetase did not alter the plasma fibrinogen response to arachidonic acid. Indomethacin did not inhibit plasma fibrinogen elevations following ACTH or endotoxin infusion, or subcutaneous turpentine injection. Intravenous infusion of two cyclic ether prostaglandin endoperoxide analogs, (15S)-hydroxy-9alpha, 11alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid, and (15S)-hydroxy-11alpha, 9alpha(epoxymethano) prosta-5Z, 13E-dienoic acid, failed to increase plasma fibrinogen."}
{"id": "PMID:210683", "title": "A histochemical and ultrastructural study of adenocarcinoma of the lung.", "content": "Twenty-five cases of solitary nodular adenocarcinoma of the human lung were studied histochemically and ultrastructurally and their morphological characteristics were compared to the cells observed in the control lungs. Adenocarcinoma cells of the human lung may be classified into following four types: Type A--cells resembling the bronchial goblet cell; Type B--cells resembling the mucous cell of the bronchial gland; Type C--cells resembling the type II alveolar lining cell; and Type D--cells resembling the nonciliated bronchiolar cell. Twenty-one cases belonging to Type D (84%) and two cases to Type B (8%), and one case each to Types A (4%) and C (4%). For the histogenesis of adenocarcinoma of the human lung, nonciliated bronchiolar epithelium may be the most important. A comparison of 10 cases of bronchiolo-alveolar carcinoma with 15 cases of ordinary (acinar and papillary) adenocarcinoma revealed no clear differences either histochemically or ultrastructurally.", "contents": "A histochemical and ultrastructural study of adenocarcinoma of the lung. Twenty-five cases of solitary nodular adenocarcinoma of the human lung were studied histochemically and ultrastructurally and their morphological characteristics were compared to the cells observed in the control lungs. Adenocarcinoma cells of the human lung may be classified into following four types: Type A--cells resembling the bronchial goblet cell; Type B--cells resembling the mucous cell of the bronchial gland; Type C--cells resembling the type II alveolar lining cell; and Type D--cells resembling the nonciliated bronchiolar cell. Twenty-one cases belonging to Type D (84%) and two cases to Type B (8%), and one case each to Types A (4%) and C (4%). For the histogenesis of adenocarcinoma of the human lung, nonciliated bronchiolar epithelium may be the most important. A comparison of 10 cases of bronchiolo-alveolar carcinoma with 15 cases of ordinary (acinar and papillary) adenocarcinoma revealed no clear differences either histochemically or ultrastructurally."}
{"id": "PMID:210684", "title": "Malignant fibrous histiocytoma. Clinicopathologic and ultrastructural study of 12 cases.", "content": "The clinical and pathologic findings of 12 cases of malignant fibrous histiocytoma of the soft tissues are presented. The mean age of the patients (eight males and four females) was 64 years, and there was a strong predilection for localization in the extremities (10 cases). The lesion is of rather low-grade malignancy, with metastases in only a minority of cases (three cases) but with nonetheless a marked tendency for local recurrence (nine cases). Histologically, the essential feature of the tumor is its biphasic composition with both histiocytic and fibroblastic components, the latter showing a characteristic storiform pattern. In addition, a variable number of xanthomatous cells and multinucleated giant cells were observed. Ultrastructural studies confirmed the presence of the aforementioned cells and in addition revealed a primitive mesenchymal cell. It is suggested that this cell may be a primitive histiocyte from which the two main cellular components of the tumor arise.", "contents": "Malignant fibrous histiocytoma. Clinicopathologic and ultrastructural study of 12 cases. The clinical and pathologic findings of 12 cases of malignant fibrous histiocytoma of the soft tissues are presented. The mean age of the patients (eight males and four females) was 64 years, and there was a strong predilection for localization in the extremities (10 cases). The lesion is of rather low-grade malignancy, with metastases in only a minority of cases (three cases) but with nonetheless a marked tendency for local recurrence (nine cases). Histologically, the essential feature of the tumor is its biphasic composition with both histiocytic and fibroblastic components, the latter showing a characteristic storiform pattern. In addition, a variable number of xanthomatous cells and multinucleated giant cells were observed. Ultrastructural studies confirmed the presence of the aforementioned cells and in addition revealed a primitive mesenchymal cell. It is suggested that this cell may be a primitive histiocyte from which the two main cellular components of the tumor arise."}
{"id": "PMID:210681", "title": "Neuropathy in joggers.", "content": "We have reported upon three different mononeuropathies that we believe were directly attributable to jogging. At this time it is presumed that this complication is not common, but as jogging increases as a routine form of exercise for the general populace it is possible that more such neuropathies will be seen. Mechanical injuries in runners are well described, and it is possible that as yet unidentified mechanical factors may injure neural tissue as well.", "contents": "Neuropathy in joggers. We have reported upon three different mononeuropathies that we believe were directly attributable to jogging. At this time it is presumed that this complication is not common, but as jogging increases as a routine form of exercise for the general populace it is possible that more such neuropathies will be seen. Mechanical injuries in runners are well described, and it is possible that as yet unidentified mechanical factors may injure neural tissue as well."}
{"id": "PMID:210685", "title": "Inflammatory fibrous histiocytoma (? anthogranuloma). Report of two cases with ultrastructural observations in one.", "content": "Two cases of inflammatory fibrous histiocytoma are presented, one occupying the pleural space, and the other the retroperitoneum. One of the cases was studied with the electron microscope and confirmed the histiocytic and xanthomatous nature of the lesion. It is suggested that the term xanthogranuloma be replaced by fibrous histiocytoma, and that when a considerable inflammatory component is present in the stroma, a guarded prognosis be entertained. Ultrastructurally there are no distinctive features for the inflammatory variant of the fibrous histiocytoma.", "contents": "Inflammatory fibrous histiocytoma (? anthogranuloma). Report of two cases with ultrastructural observations in one. Two cases of inflammatory fibrous histiocytoma are presented, one occupying the pleural space, and the other the retroperitoneum. One of the cases was studied with the electron microscope and confirmed the histiocytic and xanthomatous nature of the lesion. It is suggested that the term xanthogranuloma be replaced by fibrous histiocytoma, and that when a considerable inflammatory component is present in the stroma, a guarded prognosis be entertained. Ultrastructurally there are no distinctive features for the inflammatory variant of the fibrous histiocytoma."}
{"id": "PMID:210686", "title": "Malignant cystosarcoma phylloides. Treatment and prognosis.", "content": "Twenty-six cases of malignant cystosarcoma phylloides treated at The Charity Hospital of Louisiana were reviewed. No metastases to axillary lymph nodes was observed. The lesion appears to metastasize seldom, if ever, to lymphatics, and axillary dissection is seldom required. Local recurrence was common, however, and justifies wide resection of the primary. Mortality was related more to the size of the lesion than to other findings such as skin or muscle involvement. No lesion with less than three mitoses per ten high power fields and minimal stromal atypia proved fatal. Associated neoplasia was common, particularly in the opposite breast.", "contents": "Malignant cystosarcoma phylloides. Treatment and prognosis. Twenty-six cases of malignant cystosarcoma phylloides treated at The Charity Hospital of Louisiana were reviewed. No metastases to axillary lymph nodes was observed. The lesion appears to metastasize seldom, if ever, to lymphatics, and axillary dissection is seldom required. Local recurrence was common, however, and justifies wide resection of the primary. Mortality was related more to the size of the lesion than to other findings such as skin or muscle involvement. No lesion with less than three mitoses per ten high power fields and minimal stromal atypia proved fatal. Associated neoplasia was common, particularly in the opposite breast."}
{"id": "PMID:210693", "title": "[Variation of the profile phenotype M of alpha-1-chymotrypsine : trial of interpretation (author's transl)].", "content": "Cross immunoelectrophoresis of serum A1AT (Pi M) shows \"frequent\" patterns with M2 less than M6 less than M4. Other \"particular\" patterns were found with M6 greater than M4 and M6 less than M2. The most often found patterns among the Negroid population in our study appeared dissimilar to that found among Caucasians. The \"super-gene\" concept and the variability of genetic flow may explain this difference. The \"particular\" patterns are often found in cord blood samples and in patients with hepatocarcinoma. They show similaritis between embryonic and cancerous processes. These different patterns also agree with the \"super-gene\" concept.", "contents": "[Variation of the profile phenotype M of alpha-1-chymotrypsine : trial of interpretation (author's transl)]. Cross immunoelectrophoresis of serum A1AT (Pi M) shows \"frequent\" patterns with M2 less than M6 less than M4. Other \"particular\" patterns were found with M6 greater than M4 and M6 less than M2. The most often found patterns among the Negroid population in our study appeared dissimilar to that found among Caucasians. The \"super-gene\" concept and the variability of genetic flow may explain this difference. The \"particular\" patterns are often found in cord blood samples and in patients with hepatocarcinoma. They show similaritis between embryonic and cancerous processes. These different patterns also agree with the \"super-gene\" concept."}
{"id": "PMID:210694", "title": "A rationale for treating hepatic adenoma.", "content": "Hepatic adenomas are being seen in young women taking oral contraceptives with alarming frequency. In the United States it is estimated that at least five million women are taking oral contraceptives. Physicians should consider hepatic adenoma in the differential diagnosis of all menstruating females with right upper quadrant pain. An early diagnosis and proper treatment could be life-saving.", "contents": "A rationale for treating hepatic adenoma. Hepatic adenomas are being seen in young women taking oral contraceptives with alarming frequency. In the United States it is estimated that at least five million women are taking oral contraceptives. Physicians should consider hepatic adenoma in the differential diagnosis of all menstruating females with right upper quadrant pain. An early diagnosis and proper treatment could be life-saving."}
{"id": "PMID:210696", "title": "Medical management of home hemodialysis patients.", "content": "Increased emphasis on home hemodialysis because of proposed changes in federal funding will result in dispersion of dialysis patients to areas geographically removed from a dialysis unit. Thus primary care of these patients will increasingly become the responsibility of physicians having little previous contact with dialysis. We review the diagnosis and treatment of common problems in the dialysis patient with emphasis on the major problem areas of vascular access and the cardiovascular, hematologic, and osseous complications of renal failure.", "contents": "Medical management of home hemodialysis patients. Increased emphasis on home hemodialysis because of proposed changes in federal funding will result in dispersion of dialysis patients to areas geographically removed from a dialysis unit. Thus primary care of these patients will increasingly become the responsibility of physicians having little previous contact with dialysis. We review the diagnosis and treatment of common problems in the dialysis patient with emphasis on the major problem areas of vascular access and the cardiovascular, hematologic, and osseous complications of renal failure."}
{"id": "PMID:210700", "title": "Splenoperitoneal anastomoses after application of collagenase to the splenic capsule of rats.", "content": "In 200 Wistar rats the spleen was transposed into a pouch between the muscle layers of the left abdominal wall. Collagenase powder was applied to the spleen surface. After 12 to 24 hours an acute haemorrhagic inflammation was seen. Collaterals developed from the splenic parenchyma to the abdominal wall from the 10th day. They connected the portal venous system with the caval system.", "contents": "Splenoperitoneal anastomoses after application of collagenase to the splenic capsule of rats. In 200 Wistar rats the spleen was transposed into a pouch between the muscle layers of the left abdominal wall. Collagenase powder was applied to the spleen surface. After 12 to 24 hours an acute haemorrhagic inflammation was seen. Collaterals developed from the splenic parenchyma to the abdominal wall from the 10th day. They connected the portal venous system with the caval system."}
{"id": "PMID:210701", "title": "Adhesive arachnoiditis after lumbar myelography.", "content": "Of 1500 myelographies, 99 patients had subsequent myelographies from which the prevalence of adhesive arachnoiditis caused by the initial investigation could be calculated. Three different water-soluble contrast agents had been used in the initial study: Kontrast U (800 patients), Dimer-X (400 patients), and Conray (300 patients) and the subsets of patients restudied represented 6%, 8% and 8% respectively of the whole series. After the first myelography 68 patients had no operation, 31 patients had hemilaminectomy. Conray produced arachnoid changes in 71% of the nonoperated patients. This differed significantly from the 43% caused by Kontrast U, and the 27% evoked by Dimer-X. The same trend was evident in the operated subset. The severity of the arachnoid changes was greater after Conray. Analysis of the iodine content of the different contrast media and comparison with similar series suggested that hyperosmolarity of the agent was responsible for the changes.", "contents": "Adhesive arachnoiditis after lumbar myelography. Of 1500 myelographies, 99 patients had subsequent myelographies from which the prevalence of adhesive arachnoiditis caused by the initial investigation could be calculated. Three different water-soluble contrast agents had been used in the initial study: Kontrast U (800 patients), Dimer-X (400 patients), and Conray (300 patients) and the subsets of patients restudied represented 6%, 8% and 8% respectively of the whole series. After the first myelography 68 patients had no operation, 31 patients had hemilaminectomy. Conray produced arachnoid changes in 71% of the nonoperated patients. This differed significantly from the 43% caused by Kontrast U, and the 27% evoked by Dimer-X. The same trend was evident in the operated subset. The severity of the arachnoid changes was greater after Conray. Analysis of the iodine content of the different contrast media and comparison with similar series suggested that hyperosmolarity of the agent was responsible for the changes."}
{"id": "PMID:210703", "title": "[Calcium, cGMP and cAMP roles in thyroid regulation (author's transl)].", "content": "Cholinergic agents induce an accumulation of cGMP in thyroid tissue and inhibit cAMP accumulation and thyroid hormone secretion resulting from TSH action. The aim of the present work was to determine the respective roles of Ca++ and/or cGMP in these actions. The results show that two complementary mechanisms may be demonstrated: 1) cGMP activates phosphodiesterase activity and cAMP hydrolysis. 2) Independently of cyclic nucleotide concentrations, increased intracytoplasmic Ca++ directly inhibits TSH induced stimulated hormone secretion.", "contents": "[Calcium, cGMP and cAMP roles in thyroid regulation (author's transl)]. Cholinergic agents induce an accumulation of cGMP in thyroid tissue and inhibit cAMP accumulation and thyroid hormone secretion resulting from TSH action. The aim of the present work was to determine the respective roles of Ca++ and/or cGMP in these actions. The results show that two complementary mechanisms may be demonstrated: 1) cGMP activates phosphodiesterase activity and cAMP hydrolysis. 2) Independently of cyclic nucleotide concentrations, increased intracytoplasmic Ca++ directly inhibits TSH induced stimulated hormone secretion."}
{"id": "PMID:210699", "title": "[The cardiovascular manifestations of mixed hyperlipidaemia. Revision of a series of 950 cases (author's transl)].", "content": "The cardiovascular consequences of mixed hyperlipideamia have been determined using a very large series of 950 cases. The early development and the prevalence of complications renders the disease severe, even in its minor forms of the grave forms of essential hypercholesterolaemia. Certain special features are worthy of mention:--the total loss of any parallelism between the biological severity and the development of vascular complications;--the probable role of slow pre-beta-lipoprotein in the determination of complications above all forms resistant to therapeutic reduction where its persistence is remarkable, which justifies the addition to known electrophoretic types III and II b a type, in the opinion of the authors just as common, with pre-beta-lipoprotein without any increase in L.D.L.", "contents": "[The cardiovascular manifestations of mixed hyperlipidaemia. Revision of a series of 950 cases (author's transl)]. The cardiovascular consequences of mixed hyperlipideamia have been determined using a very large series of 950 cases. The early development and the prevalence of complications renders the disease severe, even in its minor forms of the grave forms of essential hypercholesterolaemia. Certain special features are worthy of mention:--the total loss of any parallelism between the biological severity and the development of vascular complications;--the probable role of slow pre-beta-lipoprotein in the determination of complications above all forms resistant to therapeutic reduction where its persistence is remarkable, which justifies the addition to known electrophoretic types III and II b a type, in the opinion of the authors just as common, with pre-beta-lipoprotein without any increase in L.D.L."}
{"id": "PMID:210704", "title": "Action of thyrotropin on phosphate incorporation into thyroid proteins in vitro.", "content": "It is now well established that cAMP is the intracellular mediator of many effects of thyrotropin on the thyroid. Greengard has postulated that all the effects of cAMP inside the cell are secondary to the phosphorylation of proteins by cAMP activated protein kinase(s). The purpose of our work is to define, in an intact cell system, the nature of the thyroid proteins, the phosphorylation of which is stimulated by cAMP and TSH.", "contents": "Action of thyrotropin on phosphate incorporation into thyroid proteins in vitro. It is now well established that cAMP is the intracellular mediator of many effects of thyrotropin on the thyroid. Greengard has postulated that all the effects of cAMP inside the cell are secondary to the phosphorylation of proteins by cAMP activated protein kinase(s). The purpose of our work is to define, in an intact cell system, the nature of the thyroid proteins, the phosphorylation of which is stimulated by cAMP and TSH."}
{"id": "PMID:210705", "title": "[Biochemical study of normal and abnormal thyroid cells in tissue culture (author's transl)].", "content": "Thyrotropin induces the formation of a follicular structure of thyroid cells in tissue culture. It produces an increase in cyclic AMP content of thyrotropin treated cells. Thyrotropin induces on increase in iodine incorporation with the appearance of iodinated proteins which are mostly 19 S. thyroglobulin. In goiters, the level of cyclic AMP and the stimulation with thyrotropin differs from normal conditions indicating differences in cell metabolism and differences in the properties of the receptor. Thyrotropin also gives an increase in uridine incorporation in RNA and on increase not only in poly A but also in poly A-RNA associated with heavy polysomes. The level of poly A is higher in toxic adenoma and lower in microfollicular adenoma as compared to colloido nodular goiter which is in good agreement with our knowledge of thyroid cell metabolism.", "contents": "[Biochemical study of normal and abnormal thyroid cells in tissue culture (author's transl)]. Thyrotropin induces the formation of a follicular structure of thyroid cells in tissue culture. It produces an increase in cyclic AMP content of thyrotropin treated cells. Thyrotropin induces on increase in iodine incorporation with the appearance of iodinated proteins which are mostly 19 S. thyroglobulin. In goiters, the level of cyclic AMP and the stimulation with thyrotropin differs from normal conditions indicating differences in cell metabolism and differences in the properties of the receptor. Thyrotropin also gives an increase in uridine incorporation in RNA and on increase not only in poly A but also in poly A-RNA associated with heavy polysomes. The level of poly A is higher in toxic adenoma and lower in microfollicular adenoma as compared to colloido nodular goiter which is in good agreement with our knowledge of thyroid cell metabolism."}
{"id": "PMID:210706", "title": "Growth hormone secretion in Addison's disease.", "content": "Growth hormone secretion has been evaluated in patients with Addison's disease given T.R.H., A.C.T.H. or Glucagon i.v., or L-DOPA p.o. In those with the idiopathic, auto-immune variety the mean response to glucagon and L-DOPA was reduced when compared with that documented for patients in whom tuberculosis caused the lesion. Growth hormone plasma concentrations barely changed after T.R.H. and A.C.T.H., irrespective of the aetiology of the disease.", "contents": "Growth hormone secretion in Addison's disease. Growth hormone secretion has been evaluated in patients with Addison's disease given T.R.H., A.C.T.H. or Glucagon i.v., or L-DOPA p.o. In those with the idiopathic, auto-immune variety the mean response to glucagon and L-DOPA was reduced when compared with that documented for patients in whom tuberculosis caused the lesion. Growth hormone plasma concentrations barely changed after T.R.H. and A.C.T.H., irrespective of the aetiology of the disease."}
{"id": "PMID:210702", "title": "Clinical response to therapeutic agents in poisoning from mercury vapor.", "content": "Exposure to mercury vapors for an hour per working day over a period of 13 years produced in a thermometer manufacturer severe signs and symptoms of mercury poisoning. Complete disability developed insidiously over the last six months of employment. During the first two months of observation, the patient was treated in succession with three chelating agents: 2,3-dimercapto-l-propanol (BAL), D-penicillamine and sodium diethyldithiocarbamate (Dithiocarb). Each agent was administered initially for a period of approximately two weeks. A second course of therapy with BAL was administered for three days. Of the three complexing agents used, BAL gave the most dramatically favorable clinical response and yielded the highest urinary excretions of mercury. Dithiocarb was partially effective; d-pencillamine proved to be essentially ineffective. Analyses of the patient's sweat indicated that appreciable amounts of mercury were excreted by this route. Following the alleviation of the severe symptoms by BAL, the patient was placed on a regimen of daily sweats and physio-therapy for a protracted period of several months. On this latter regimen, the mercury levels in the urine, blood serum and sweat were decreased to within the normal ranges of values. The patient made a complete and uneventful recovery. In patients encountering psychotic and neurological disorders of undetermined etiology, consideration should be given to unsuspected or masked chronic exposure to mercury vapors as a possible cause.", "contents": "Clinical response to therapeutic agents in poisoning from mercury vapor. Exposure to mercury vapors for an hour per working day over a period of 13 years produced in a thermometer manufacturer severe signs and symptoms of mercury poisoning. Complete disability developed insidiously over the last six months of employment. During the first two months of observation, the patient was treated in succession with three chelating agents: 2,3-dimercapto-l-propanol (BAL), D-penicillamine and sodium diethyldithiocarbamate (Dithiocarb). Each agent was administered initially for a period of approximately two weeks. A second course of therapy with BAL was administered for three days. Of the three complexing agents used, BAL gave the most dramatically favorable clinical response and yielded the highest urinary excretions of mercury. Dithiocarb was partially effective; d-pencillamine proved to be essentially ineffective. Analyses of the patient's sweat indicated that appreciable amounts of mercury were excreted by this route. Following the alleviation of the severe symptoms by BAL, the patient was placed on a regimen of daily sweats and physio-therapy for a protracted period of several months. On this latter regimen, the mercury levels in the urine, blood serum and sweat were decreased to within the normal ranges of values. The patient made a complete and uneventful recovery. In patients encountering psychotic and neurological disorders of undetermined etiology, consideration should be given to unsuspected or masked chronic exposure to mercury vapors as a possible cause."}
{"id": "PMID:210707", "title": "Mixed longitudinal data on skeletal age from a group of Dutch children living in Utrecht and surroundings.", "content": "The height and weight of 1132 children, aged 8.0--17.0 years studied in 1970--72 in a semi-longitudinal survey in the Dental Institute of Utrecht, are compared with similar data from the national Dutch survey of 1965. Children measured in 1970--72 are somewhat taller than, but have the same weight as, those of the same ages in 1965. The increase in height since 1965 appears to be primarily due to the sub-group enrolled in vocational (as opposed to general) education. The maximal yearly increments in height and weight of the girls occurred between 11.0 and 12.0 years, and between 12.0 and 13.0 years, respectively. For boys the maximal increments in height and weight occurred between 14.0 and 15.0 years. Using the Tanner-Whitehouse 2 method, the skeletal age of this group of children was determined and compared with similar data from British standards. The results of the twenty-bone skeletal age indicated that Dutch boys, and to a lesser extent, girls, mature slightly later than English children at the approximate age range of 10.0--13.0 years and 8.0--10.0 years, respectively. After this age they follow roughly the growth curve of the British standards. The annual increment in skeletal age, plotted with chronological age as a time base, shows a peak for boys as well as girls that coincides with peak height velocity. The Carpal skeletal ages of boys and girls are almost identical in all age-groups with those of the British children, while the RUS skeletal age shows a much greater variability in the different age-groups. The variation in mean velocity (maturity points) between the two populations appears to be more marked in the RUS bones than in the round bones. The TW 1 skeletal age of each subject was plotted against the total TW 2, RUS or Carpal skeletal ages of the same individual. Equations are given for converting TW 1 skeletal ages into total TW 2 or RUS skeletal ages.", "contents": "Mixed longitudinal data on skeletal age from a group of Dutch children living in Utrecht and surroundings. The height and weight of 1132 children, aged 8.0--17.0 years studied in 1970--72 in a semi-longitudinal survey in the Dental Institute of Utrecht, are compared with similar data from the national Dutch survey of 1965. Children measured in 1970--72 are somewhat taller than, but have the same weight as, those of the same ages in 1965. The increase in height since 1965 appears to be primarily due to the sub-group enrolled in vocational (as opposed to general) education. The maximal yearly increments in height and weight of the girls occurred between 11.0 and 12.0 years, and between 12.0 and 13.0 years, respectively. For boys the maximal increments in height and weight occurred between 14.0 and 15.0 years. Using the Tanner-Whitehouse 2 method, the skeletal age of this group of children was determined and compared with similar data from British standards. The results of the twenty-bone skeletal age indicated that Dutch boys, and to a lesser extent, girls, mature slightly later than English children at the approximate age range of 10.0--13.0 years and 8.0--10.0 years, respectively. After this age they follow roughly the growth curve of the British standards. The annual increment in skeletal age, plotted with chronological age as a time base, shows a peak for boys as well as girls that coincides with peak height velocity. The Carpal skeletal ages of boys and girls are almost identical in all age-groups with those of the British children, while the RUS skeletal age shows a much greater variability in the different age-groups. The variation in mean velocity (maturity points) between the two populations appears to be more marked in the RUS bones than in the round bones. The TW 1 skeletal age of each subject was plotted against the total TW 2, RUS or Carpal skeletal ages of the same individual. Equations are given for converting TW 1 skeletal ages into total TW 2 or RUS skeletal ages."}
{"id": "PMID:210709", "title": "[Polymyxin B biosynthesis and tricarboxylic acid cycle enzymatic activity].", "content": "Activity of pyruvate dehydrogenase (PDG), isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase and malate dehydrogenase was found in the extracts of the cells of Bac. polymyxa 153, an organism producing polymyxin B. Dependence of the activity of the above enzymes on the carbon source in the medium, aeration conditions, strain features and culture age was shown. A low level of polymyxin B biosynthesis was observed at high activity of PDG and dehydrogenases of the tricarbonic acid cycle. Increased antibiotic production was recorded against the background of decreases values of the above enzyme activities.", "contents": "[Polymyxin B biosynthesis and tricarboxylic acid cycle enzymatic activity]. Activity of pyruvate dehydrogenase (PDG), isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase and malate dehydrogenase was found in the extracts of the cells of Bac. polymyxa 153, an organism producing polymyxin B. Dependence of the activity of the above enzymes on the carbon source in the medium, aeration conditions, strain features and culture age was shown. A low level of polymyxin B biosynthesis was observed at high activity of PDG and dehydrogenases of the tricarbonic acid cycle. Increased antibiotic production was recorded against the background of decreases values of the above enzyme activities."}
{"id": "PMID:210710", "title": "[Interferonogenic and antiviral activity of the double-stranded replicative form of phage f2 RNA in tissue culture and on animals].", "content": "Biological activity of a new natural interferon inductor, the replicative RNA form of phage f2 (RFf2) was studied. A possibility of using RFf2 for production of highly active interferon under conditions of superinduction providing an increase in the interferon yield by to 256--512 times as compared to the control samples was shown. The protective interferonogenic and antiviral effect of RFf2 in mice infected with Semliki forest virus (SFV) and tickborne encephalitis virus (TBEV) was studied on administration of the inductor by various routes. It was found that intraperitoneal administration of RFf2 in a dose of 10 gamma per a mouse protected the infected animals from death. It was accompanied by production of up to 1280 units/ml of interferon in the blood serum of the animals. Maximum protection of the animals from death under conditions of the experiment (80 per cent on infection with SFV and 65 per cent on infection with TBEV) was observed when the preparation was administered twice: 4 hours after the infection. Combined use of RFf2 with chemotherapeutics (rimantadine) increased the protective effect both in the tissue culture and in vivo.", "contents": "[Interferonogenic and antiviral activity of the double-stranded replicative form of phage f2 RNA in tissue culture and on animals]. Biological activity of a new natural interferon inductor, the replicative RNA form of phage f2 (RFf2) was studied. A possibility of using RFf2 for production of highly active interferon under conditions of superinduction providing an increase in the interferon yield by to 256--512 times as compared to the control samples was shown. The protective interferonogenic and antiviral effect of RFf2 in mice infected with Semliki forest virus (SFV) and tickborne encephalitis virus (TBEV) was studied on administration of the inductor by various routes. It was found that intraperitoneal administration of RFf2 in a dose of 10 gamma per a mouse protected the infected animals from death. It was accompanied by production of up to 1280 units/ml of interferon in the blood serum of the animals. Maximum protection of the animals from death under conditions of the experiment (80 per cent on infection with SFV and 65 per cent on infection with TBEV) was observed when the preparation was administered twice: 4 hours after the infection. Combined use of RFf2 with chemotherapeutics (rimantadine) increased the protective effect both in the tissue culture and in vivo."}
{"id": "PMID:210711", "title": "[Serum enzymatic activity in oncological patients treated with carminomycin].", "content": "Karminomycin effect on the activity of some serum enzymes, such as hexokinase (HK), lactate dehydrogenase (LDG), its isoenzymes and glucose-6-phosphatase (G-6-P-ase) was studied. Biochemical assays were applied to 52 patients with neglected malignant tumors. The course dose of the drug was on the average 72mg. The objective antitumor effect was registered in 15 patients. A reliable increase in the values of LDG-5 and G-6-P-ase was observed after the treatment course in the combined group consisting of all the patients subjected to the biochemical assay. Normalization of the serum enzyme spectrum was observed in 15 patients effectively treated with karminomycin: activity of HK and the cathode fractions of LDG decreased. When treatment with karminomycin was ineffective (37 cases), the changes in the enzymatic activity recorded before the treatment further aggraviated. It was found that the level of G-6-P-ase in the patients' treated with karminomycin increased independent of the treatment effect which was probably associated with its toxic effect on the liver. The increase was reversible.", "contents": "[Serum enzymatic activity in oncological patients treated with carminomycin]. Karminomycin effect on the activity of some serum enzymes, such as hexokinase (HK), lactate dehydrogenase (LDG), its isoenzymes and glucose-6-phosphatase (G-6-P-ase) was studied. Biochemical assays were applied to 52 patients with neglected malignant tumors. The course dose of the drug was on the average 72mg. The objective antitumor effect was registered in 15 patients. A reliable increase in the values of LDG-5 and G-6-P-ase was observed after the treatment course in the combined group consisting of all the patients subjected to the biochemical assay. Normalization of the serum enzyme spectrum was observed in 15 patients effectively treated with karminomycin: activity of HK and the cathode fractions of LDG decreased. When treatment with karminomycin was ineffective (37 cases), the changes in the enzymatic activity recorded before the treatment further aggraviated. It was found that the level of G-6-P-ase in the patients' treated with karminomycin increased independent of the treatment effect which was probably associated with its toxic effect on the liver. The increase was reversible."}
{"id": "PMID:210712", "title": "Cutaneous metastases from hepatomas.", "content": "Three cases of hepatomas metastasized to the skin in a series of 88 patients with hepatomas. The skin metastases differed from the usual dermal nodules, such as fibromas, inflammatory granulomas, and adnexal tumors, by their rather sudden appearance as solitary or multiple, nonulcerative, painless, firm, reddish-blue nodules on the scalp, chest, and shoulder. Biopsies of these nodules were necessary in order to confirm the diagnosis of the cutaneous metastases, which appeared before the primary tumors were recognized. Microscopically, the skin tumors were adenocarcinomas in two instances and hepatocellular carcinoma in one. The skin metastases were a late manifestation of the primary tumors; the patients died within three weeks to six months after the appearance of skin tumors. Necropsies showed widespread metastases.", "contents": "Cutaneous metastases from hepatomas. Three cases of hepatomas metastasized to the skin in a series of 88 patients with hepatomas. The skin metastases differed from the usual dermal nodules, such as fibromas, inflammatory granulomas, and adnexal tumors, by their rather sudden appearance as solitary or multiple, nonulcerative, painless, firm, reddish-blue nodules on the scalp, chest, and shoulder. Biopsies of these nodules were necessary in order to confirm the diagnosis of the cutaneous metastases, which appeared before the primary tumors were recognized. Microscopically, the skin tumors were adenocarcinomas in two instances and hepatocellular carcinoma in one. The skin metastases were a late manifestation of the primary tumors; the patients died within three weeks to six months after the appearance of skin tumors. Necropsies showed widespread metastases."}
{"id": "PMID:210713", "title": "Kaposi's varicelliform eruption in mycosis fungoides.", "content": "Kaposi's varicelliform eruption, caused by herpes simplex type 1, developed in a patient with mycosis fungoides four days after initiation of photochemotherapy with methoxsalen plus long-wave ultraviolet light (PUVA). He had a history of recurrent localized herpes infection. Vidarabine (adenine arabinoside) was used as treatment. Rechallenge with PUVA did not provoke another herpes infection. Kaposi's varicelliform eruption is rare in mycosis fungoides. Vidarabine may prove to be useful in the treatment of widespread herpes simplex.", "contents": "Kaposi's varicelliform eruption in mycosis fungoides. Kaposi's varicelliform eruption, caused by herpes simplex type 1, developed in a patient with mycosis fungoides four days after initiation of photochemotherapy with methoxsalen plus long-wave ultraviolet light (PUVA). He had a history of recurrent localized herpes infection. Vidarabine (adenine arabinoside) was used as treatment. Rechallenge with PUVA did not provoke another herpes infection. Kaposi's varicelliform eruption is rare in mycosis fungoides. Vidarabine may prove to be useful in the treatment of widespread herpes simplex."}
{"id": "PMID:210714", "title": "Multiple periorbital fibrous histiocytomas: a light and electron microscopic study.", "content": "Recurrent, bilateral, multiple, periorbital fibrous histiocytomas occurred in a 62-year-old woman. There were no associated serum lipid abnormalities. Histologically, the tumor was composed of an admixture of lipid-laden histiocytes and fibroblasts with a variable amount of collagen production. In many areas the fibroblasts were arranged in a storiform pattern. No cytologic evidence of malignancy was observed. Ultrastructural studies of the tumor showed histiocytic cells with a variable amount of lipid in the cytoplasm and fibroblasts with mild to moderate collagen production. Differential diagnosis and histogenesis are discussed.", "contents": "Multiple periorbital fibrous histiocytomas: a light and electron microscopic study. Recurrent, bilateral, multiple, periorbital fibrous histiocytomas occurred in a 62-year-old woman. There were no associated serum lipid abnormalities. Histologically, the tumor was composed of an admixture of lipid-laden histiocytes and fibroblasts with a variable amount of collagen production. In many areas the fibroblasts were arranged in a storiform pattern. No cytologic evidence of malignancy was observed. Ultrastructural studies of the tumor showed histiocytic cells with a variable amount of lipid in the cytoplasm and fibroblasts with mild to moderate collagen production. Differential diagnosis and histogenesis are discussed."}
{"id": "PMID:210715", "title": "S\u00e9zary's syndrome: report of a case showing peripheral neuropathy and bone marrow fibrosis.", "content": "A case of S\u00e9zary's syndrome occurred in a 45-year-old man. The unusual noteworthy features in this case are dermal sclerosis, peripheral neuropathy, and bone marrow fibrosis. In two other cases, reviewed here, there was a tendency to fibrosis; therefore, we propose that this process may be an integral part of S\u00e9zary's syndrome.", "contents": "S\u00e9zary's syndrome: report of a case showing peripheral neuropathy and bone marrow fibrosis. A case of S\u00e9zary's syndrome occurred in a 45-year-old man. The unusual noteworthy features in this case are dermal sclerosis, peripheral neuropathy, and bone marrow fibrosis. In two other cases, reviewed here, there was a tendency to fibrosis; therefore, we propose that this process may be an integral part of S\u00e9zary's syndrome."}
{"id": "PMID:210721", "title": "Isolated ACTH deficiency. Metabolic and endocrine studies in a 7-year-old boy.", "content": "Metabolic and endocrine studies on a 7-year-old boy who presented with hypoglycaemic convulsions are reported in detail, proving the diagnosis of isolated ACTH deficiency--a rare cause of hypoglycaemia in childhood. Adrenaline secretion during insulin-induced hypoglycaemia was reduced. Low blood alanine levels occurred during starvation-induced hypoglycaemia, together with raised total blood ketone bodies; blood glucose did not increase adequately after oral alanine at this time. Hypoglycaemia in isolated ACTH deficiency appears to be due to a combination of impaired alanine mobilisation and a decreased rate of gluconeogenesis.", "contents": "Isolated ACTH deficiency. Metabolic and endocrine studies in a 7-year-old boy. Metabolic and endocrine studies on a 7-year-old boy who presented with hypoglycaemic convulsions are reported in detail, proving the diagnosis of isolated ACTH deficiency--a rare cause of hypoglycaemia in childhood. Adrenaline secretion during insulin-induced hypoglycaemia was reduced. Low blood alanine levels occurred during starvation-induced hypoglycaemia, together with raised total blood ketone bodies; blood glucose did not increase adequately after oral alanine at this time. Hypoglycaemia in isolated ACTH deficiency appears to be due to a combination of impaired alanine mobilisation and a decreased rate of gluconeogenesis."}
{"id": "PMID:210722", "title": "Congenital cytomegalovirus infection in newborn infants of mothers infected before pregnancy.", "content": "The rate of congenital cytomegalovirus (CMV) infection was studied in newborn infants in an African population in which all adults had experienced primary CMV infection during childhood. Viruria within the first 12 hours after delivery was taken as evidence of prenatal CMV infection. 28 of 2032 newborn infants examined had viruria, giving a rate of 1.4% congenital CMV infection. The presence of meternal serum antibody therefore appears not to protect the fetus from intrauterine infection. Either reactivation of latent maternal CMV infection or recurrence of infection during pregnancy despite the presence of serum antibodies may explain these findings. Whether the long-term effects of CMV infection acquired in utero differ in cases of primary maternal infection from those due to reactivated or recurrent infection in seropositive mothers, remains undecided. Thus, the value of a live CMV vaccine to prevent prenatal CMV infection may be questioned.", "contents": "Congenital cytomegalovirus infection in newborn infants of mothers infected before pregnancy. The rate of congenital cytomegalovirus (CMV) infection was studied in newborn infants in an African population in which all adults had experienced primary CMV infection during childhood. Viruria within the first 12 hours after delivery was taken as evidence of prenatal CMV infection. 28 of 2032 newborn infants examined had viruria, giving a rate of 1.4% congenital CMV infection. The presence of meternal serum antibody therefore appears not to protect the fetus from intrauterine infection. Either reactivation of latent maternal CMV infection or recurrence of infection during pregnancy despite the presence of serum antibodies may explain these findings. Whether the long-term effects of CMV infection acquired in utero differ in cases of primary maternal infection from those due to reactivated or recurrent infection in seropositive mothers, remains undecided. Thus, the value of a live CMV vaccine to prevent prenatal CMV infection may be questioned."}
{"id": "PMID:210723", "title": "Interaction of ACTH, corticosterone and cyclic nucleotides in Harding-Passey melanoma melanogenesis.", "content": "The acute in vitro action of adrenocorticotropin (ACTH) and corticosterone alone and in combination were determined in the Harding-Passey (HP) melanoma grown in vivo. Hormone treated melanoma dice (5--240 min) were analyzed for tyrosinase activity, cyclic AMP (cAMP) and cyclic GMP (cGMP). ACTH elevated cAMP and cGMP levels 20- and 13-fold, respectively, in the HP melanoma. However, these large increases in cyclic nucleotide levels were accompanied by only a 49% increase in tyrosinase activity. Corticosterone elicited a similar response. ACTH plus corticosterone produced an early cAMP and cGMP peak followed by depression. ACTH plus corticosterone stimulated tyrosinase activity coincident with the early cyclic nucleotide peak followed by a drop in tyrosinase activity which was subsequently elevated. The results indicate that neither cAMP nor cGMP are the sole modulators of tyrosinase activity and suggest the interaction of ACTH, corticosterone and cyclic nucleotides in the regulation of melanoma tyrosinase activity.", "contents": "Interaction of ACTH, corticosterone and cyclic nucleotides in Harding-Passey melanoma melanogenesis. The acute in vitro action of adrenocorticotropin (ACTH) and corticosterone alone and in combination were determined in the Harding-Passey (HP) melanoma grown in vivo. Hormone treated melanoma dice (5--240 min) were analyzed for tyrosinase activity, cyclic AMP (cAMP) and cyclic GMP (cGMP). ACTH elevated cAMP and cGMP levels 20- and 13-fold, respectively, in the HP melanoma. However, these large increases in cyclic nucleotide levels were accompanied by only a 49% increase in tyrosinase activity. Corticosterone elicited a similar response. ACTH plus corticosterone produced an early cAMP and cGMP peak followed by depression. ACTH plus corticosterone stimulated tyrosinase activity coincident with the early cyclic nucleotide peak followed by a drop in tyrosinase activity which was subsequently elevated. The results indicate that neither cAMP nor cGMP are the sole modulators of tyrosinase activity and suggest the interaction of ACTH, corticosterone and cyclic nucleotides in the regulation of melanoma tyrosinase activity."}
{"id": "PMID:210724", "title": "DNA-binding proteins of psoriatic scales III. Biochemical characterisation as non-histone-proteins.", "content": "Histone and non-histone-proteins (NHP) are proteins with a specific affinity to DNA; each group is involved in the regulation of gene expression in its own way. To investigate molecular biologic processes at psoriasis, DNA-binding proteins (DBP) were isolated from psoriatic scales. During this work the proportions of histone and NHP of the DBP fractions were examined. Using two different methods (Bio Rex 70-chromatography and isoelectrofocussing), it was found that the isolated DBP contain only acidic proteins. Likewise, the composition of amino acids is comparable with those of acidic, nuclear proteins of other tissues. Thus the isolated DBP represent to its greatest extent acidic, chromosomal NHP, which obviously are derived from the preserved nuclei of the parakeratotic scale layer.", "contents": "DNA-binding proteins of psoriatic scales III. Biochemical characterisation as non-histone-proteins. Histone and non-histone-proteins (NHP) are proteins with a specific affinity to DNA; each group is involved in the regulation of gene expression in its own way. To investigate molecular biologic processes at psoriasis, DNA-binding proteins (DBP) were isolated from psoriatic scales. During this work the proportions of histone and NHP of the DBP fractions were examined. Using two different methods (Bio Rex 70-chromatography and isoelectrofocussing), it was found that the isolated DBP contain only acidic proteins. Likewise, the composition of amino acids is comparable with those of acidic, nuclear proteins of other tissues. Thus the isolated DBP represent to its greatest extent acidic, chromosomal NHP, which obviously are derived from the preserved nuclei of the parakeratotic scale layer."}
{"id": "PMID:210725", "title": "Cyclic AMP and prostaglandin E in perfusates of rat hind paws during the development of adjuvant arthritis.", "content": "The contralateral uninjected hind paws of rats which had been injected with Freund's complete (FCA) or incomplete (FIA) adjuvant 10,14, 18, or 22 days previously were perfused under urethane anaesthesia using a stainless steel coaxial catheter. In one series of experiments cyclic AMP (cAMP) levels were determined after a 2-hour perfusion. cAMP levels were also determined in rats treated on days 16-22 with either prostaglandin E(1) (PGE(1)) (500 mug/kg per day subcutaneously) or saline. When compared with control rats injected with FIA, after 22 days, cAMP levels in FCA-injected rats fell between days 10 and 18 and then rose between days 18 and 22. After PGE(1) treatment, paw volume on day 22 increased in rats injected with FCA, but cAMP levels were not significantly altered when compared with day 22 FCA-injected controls treated with saline. In a second series of experiments, using a slightly modified perfusion method, PG levels in extracts of 30-minute perfusates were determined after chromatography and bioassay. Protein levels and paw volume were also measured. No PGF was detectable in any perfusate. Changes in PGE levels in FCA-injected animals paralleled changes in paw volume, increasing from day 14 and reaching a maximum on day 22. Both parameters remained unchanged in FIA-injected rats. Protein levels in perfusates from FCA-injected animals were significantly greater than FIA-injected controls only on day 22. We suggest that the early changes in cAMP reflect the infiltration of activated leucocytes into the inflamed joint and that the increase in PGE is attributable to lysosomal enzyme activity. Later increases in cAMP are attributable both to the increasing PGE levels and to other changes in cellular activation. We suggest that high levels of PGE contribute to tissue damage which is reflected in raised protein levels.", "contents": "Cyclic AMP and prostaglandin E in perfusates of rat hind paws during the development of adjuvant arthritis. The contralateral uninjected hind paws of rats which had been injected with Freund's complete (FCA) or incomplete (FIA) adjuvant 10,14, 18, or 22 days previously were perfused under urethane anaesthesia using a stainless steel coaxial catheter. In one series of experiments cyclic AMP (cAMP) levels were determined after a 2-hour perfusion. cAMP levels were also determined in rats treated on days 16-22 with either prostaglandin E(1) (PGE(1)) (500 mug/kg per day subcutaneously) or saline. When compared with control rats injected with FIA, after 22 days, cAMP levels in FCA-injected rats fell between days 10 and 18 and then rose between days 18 and 22. After PGE(1) treatment, paw volume on day 22 increased in rats injected with FCA, but cAMP levels were not significantly altered when compared with day 22 FCA-injected controls treated with saline. In a second series of experiments, using a slightly modified perfusion method, PG levels in extracts of 30-minute perfusates were determined after chromatography and bioassay. Protein levels and paw volume were also measured. No PGF was detectable in any perfusate. Changes in PGE levels in FCA-injected animals paralleled changes in paw volume, increasing from day 14 and reaching a maximum on day 22. Both parameters remained unchanged in FIA-injected rats. Protein levels in perfusates from FCA-injected animals were significantly greater than FIA-injected controls only on day 22. We suggest that the early changes in cAMP reflect the infiltration of activated leucocytes into the inflamed joint and that the increase in PGE is attributable to lysosomal enzyme activity. Later increases in cAMP are attributable both to the increasing PGE levels and to other changes in cellular activation. We suggest that high levels of PGE contribute to tissue damage which is reflected in raised protein levels."}
{"id": "PMID:210727", "title": "Clinical manifestations of infections with herpesviruses after kidney transplantation: a prospective study of various syndromes.", "content": "Herpesviruses infections occur commonly following kidney transplantation and immunosuppression, and contribute substantially to morbidity in the transplant recipient. In this prospective study, stomatitis, mononucleosis, hepatitis, or interstitial pneumonia occurred in 24 of 30 patients (80%) as a result of reactivation of latent herpesvirus infections, but the majority of these syndromes were self-limited and the infections were often asymptomatic. Rejection occurred significantly more frequently in CMV-infected patients, but a distinct causal relationship cannot be deduced.", "contents": "Clinical manifestations of infections with herpesviruses after kidney transplantation: a prospective study of various syndromes. Herpesviruses infections occur commonly following kidney transplantation and immunosuppression, and contribute substantially to morbidity in the transplant recipient. In this prospective study, stomatitis, mononucleosis, hepatitis, or interstitial pneumonia occurred in 24 of 30 patients (80%) as a result of reactivation of latent herpesvirus infections, but the majority of these syndromes were self-limited and the infections were often asymptomatic. Rejection occurred significantly more frequently in CMV-infected patients, but a distinct causal relationship cannot be deduced."}
{"id": "PMID:210728", "title": "The effect of glucagon on rat cardiac cyclic AMP, phosphorylase a and force of contraction.", "content": "Glucagon produced dose-dependent increases in cyclic AMP, contractile force and % phosphorylase a when injected into isolated perfused rat hearts. Time-response experiments demonstrated that the increase in cyclic AMP occurred prior to changes in the other two parameters. All glucagon effects were enhanced by perfusion of the hearts with 1.0 mM theophylline although contractile force was affected less than the other 2 events. The data lend support to the concept that increases in cyclic AMP may be involved in the inotropic effect of glucagon. It should be noted, however, that the cyclic AMP increases produced by glucagon were considerably less than those previously noted with either the catecholamines or histamine.", "contents": "The effect of glucagon on rat cardiac cyclic AMP, phosphorylase a and force of contraction. Glucagon produced dose-dependent increases in cyclic AMP, contractile force and % phosphorylase a when injected into isolated perfused rat hearts. Time-response experiments demonstrated that the increase in cyclic AMP occurred prior to changes in the other two parameters. All glucagon effects were enhanced by perfusion of the hearts with 1.0 mM theophylline although contractile force was affected less than the other 2 events. The data lend support to the concept that increases in cyclic AMP may be involved in the inotropic effect of glucagon. It should be noted, however, that the cyclic AMP increases produced by glucagon were considerably less than those previously noted with either the catecholamines or histamine."}
{"id": "PMID:210729", "title": "The K+-dependent phosphatase from human renal tissue: its properties and time dependent inhibition by ouabain.", "content": "The K+-dependent p-nitrophenyl phosphatase activity associated with human renal (Na+ + K+)-ATPase was examined for some of its kinetic properties. ATP inhibited the K+-dependent phosphatase and raised the Km for p-nitrophenylphosphate. Stimulation of the K+-dependent phosphatase by K+ was blocked by Na+ in a noncompetitive manner. Inhibition of the K+-dependent phosphatase by ouabain was dependent upon incubation time. The apparent K\u00ef was 2.0 micron.", "contents": "The K+-dependent phosphatase from human renal tissue: its properties and time dependent inhibition by ouabain. The K+-dependent p-nitrophenyl phosphatase activity associated with human renal (Na+ + K+)-ATPase was examined for some of its kinetic properties. ATP inhibited the K+-dependent phosphatase and raised the Km for p-nitrophenylphosphate. Stimulation of the K+-dependent phosphatase by K+ was blocked by Na+ in a noncompetitive manner. Inhibition of the K+-dependent phosphatase by ouabain was dependent upon incubation time. The apparent K\u00ef was 2.0 micron."}
{"id": "PMID:210730", "title": "Disordered glucose and insulin metabolism in patients with insulinoma.", "content": "The response of plasma glucose and insulin to infusion of glucose and of epinephrine plus propranolol were examined in normal subjects and in two patients with surgically proven insulin-secreting islet cell tumors. The plasma immunoreactive insulin concentration in the two patients was both inappropriate and independent of the plasma glucose concentration. Their insulin secretion was neither increased by physiologic stimulants nor decreased by pharmacologic inhibitors of insulin secretion. There are diagnostic uses for these data as well as theoretical implications. We propose a physiological approach to establish the diagnosis of insulin-secreting islet cell tumors.", "contents": "Disordered glucose and insulin metabolism in patients with insulinoma. The response of plasma glucose and insulin to infusion of glucose and of epinephrine plus propranolol were examined in normal subjects and in two patients with surgically proven insulin-secreting islet cell tumors. The plasma immunoreactive insulin concentration in the two patients was both inappropriate and independent of the plasma glucose concentration. Their insulin secretion was neither increased by physiologic stimulants nor decreased by pharmacologic inhibitors of insulin secretion. There are diagnostic uses for these data as well as theoretical implications. We propose a physiological approach to establish the diagnosis of insulin-secreting islet cell tumors."}
{"id": "PMID:210726", "title": "[Concentrations of the IgM and antibodies for the TORCH complex in the umbilical blood (author's transl)].", "content": "The Authors have found both IgM and antibodies for the TORCH complex in the umbilical blood of 1500 newborns. In 119 (7.9%) there was an increase of IgM. In 23% of these newborns there were present antibodies for rubella, in 21% antibodies for toxoplasma, in 15.9% antibodies for cytomegalovirus, and in 19.2% antibodies for herpes simplex. However there was no statistical correlation between the antibodies for the TORCH complex and the increase of IgM.", "contents": "[Concentrations of the IgM and antibodies for the TORCH complex in the umbilical blood (author's transl)]. The Authors have found both IgM and antibodies for the TORCH complex in the umbilical blood of 1500 newborns. In 119 (7.9%) there was an increase of IgM. In 23% of these newborns there were present antibodies for rubella, in 21% antibodies for toxoplasma, in 15.9% antibodies for cytomegalovirus, and in 19.2% antibodies for herpes simplex. However there was no statistical correlation between the antibodies for the TORCH complex and the increase of IgM."}
{"id": "PMID:210731", "title": "Normal jejunal cyclic nucleotide content in a patient with secretory diarrhea.", "content": "A case of chronic secretory diarrhea with elevated plasma vasoactive intestinal peptide (VIP) and serum gastrin levels is described. Plasma secretin, glucagon, insulin, and cyclic adenosine and guanine monophosphate (cAMP and (CGMP) concentrations were normal. Administration of a prostaglandin synthetase inhibitor failed to decrease the volume of diarrhea. There was no evidence of laxative abuse, antral cell hyperplasia, gastric hypersecretion, or pancreatic hypersecretion. The pancreatic histology was interpreted as islet cell hyperplasia. Jejunal tissue cAMP and cGMP concentrations were in the same range as those obtained from three control subjects. This report suggests that cyclic nucleotides may not mediate intestinal secretion in hormone-induced diarrhea.", "contents": "Normal jejunal cyclic nucleotide content in a patient with secretory diarrhea. A case of chronic secretory diarrhea with elevated plasma vasoactive intestinal peptide (VIP) and serum gastrin levels is described. Plasma secretin, glucagon, insulin, and cyclic adenosine and guanine monophosphate (cAMP and (CGMP) concentrations were normal. Administration of a prostaglandin synthetase inhibitor failed to decrease the volume of diarrhea. There was no evidence of laxative abuse, antral cell hyperplasia, gastric hypersecretion, or pancreatic hypersecretion. The pancreatic histology was interpreted as islet cell hyperplasia. Jejunal tissue cAMP and cGMP concentrations were in the same range as those obtained from three control subjects. This report suggests that cyclic nucleotides may not mediate intestinal secretion in hormone-induced diarrhea."}
{"id": "PMID:210734", "title": "[Isolation of foamy virus type II out of haematopoetic cells from baboons with haematoblastoses and from healthy animals (author's transl)].", "content": "Foamy virus Type II persists in the haematopoetic organs of 75 percent of baboons in the Suchumi flock. A mixed infection with foamy virus types I and II seems to be possible. Foamy viruses are isolated as well from monkeys with haemoblastoses as from healthy animals. New information concerning the intrauterine transmission of foamy viruses were obtained.", "contents": "[Isolation of foamy virus type II out of haematopoetic cells from baboons with haematoblastoses and from healthy animals (author's transl)]. Foamy virus Type II persists in the haematopoetic organs of 75 percent of baboons in the Suchumi flock. A mixed infection with foamy virus types I and II seems to be possible. Foamy viruses are isolated as well from monkeys with haemoblastoses as from healthy animals. New information concerning the intrauterine transmission of foamy viruses were obtained."}
{"id": "PMID:210735", "title": "[The diagnosis of the main histological types of lung cancer by means of cytological smears (author's transl)].", "content": "The paper emphasizes the possibility to distinguish types I, II and III (WHO classification) of lung cancer not only by means of single cells, but also of tissue solids in cytological smears. The morphologic criteria of tissue solids and their special patterns in the different main types of lung cancer are described.", "contents": "[The diagnosis of the main histological types of lung cancer by means of cytological smears (author's transl)]. The paper emphasizes the possibility to distinguish types I, II and III (WHO classification) of lung cancer not only by means of single cells, but also of tissue solids in cytological smears. The morphologic criteria of tissue solids and their special patterns in the different main types of lung cancer are described."}
{"id": "PMID:210736", "title": "Medullary carcinoma of the thyroid. Giant cell type.", "content": "This report presents a rare histological variation of medullary (C-cell) carcinoma of the thyroid, referred to as giant cell type, which is similar to that found in anaplastic carcinoma of the thyroid, or choriocarcinoma. The giant cells in this case possessed specific immunofluorescence for calcitonin and secretory granules in the cytoplasm. The giant cells were tumor cells of medullary carcinoma and could be distinguished from anaplastic carcinoma of the thyroid by various histological characteristics, such as nuclear invagination, an intermingled pattern of giant cells with typical small solid cells, infrequency of mitosis, and the existence of amyloid stroma.", "contents": "Medullary carcinoma of the thyroid. Giant cell type. This report presents a rare histological variation of medullary (C-cell) carcinoma of the thyroid, referred to as giant cell type, which is similar to that found in anaplastic carcinoma of the thyroid, or choriocarcinoma. The giant cells in this case possessed specific immunofluorescence for calcitonin and secretory granules in the cytoplasm. The giant cells were tumor cells of medullary carcinoma and could be distinguished from anaplastic carcinoma of the thyroid by various histological characteristics, such as nuclear invagination, an intermingled pattern of giant cells with typical small solid cells, infrequency of mitosis, and the existence of amyloid stroma."}
{"id": "PMID:210738", "title": "[Morphology of the adrenal cortex in infants with generalized adenovirus infections].", "content": "Morphometric, histological, and immunofluorescent studies were carried out with adrenal glands of 14 infants dying with generalized adenovirus infection sometimes concurrent with other acute viral respiratory diseases. Nonspecific changes were found: edema of the capsule and stroma, discomplexation of the trabeculae, circulatory disorders, delipoidization, an increase in the content of DNA and RNA in cells of the definitive cortex, resorption of the elements of the fetal cortex. The pattern of changes of morphometric values attests to increased functional activity of the adrenal cortex. The intensity of the observed changes was directly related to the duration of the disease. The results of clinico-morphological analysis confirm the importance of adrenal insufficiency in tanatogenesis in generalized adenovirus infection. In 10 cases epithelial and endothelial cells of the definitive cortex were found to have specific lesions, the so-called adenovirus cells.", "contents": "[Morphology of the adrenal cortex in infants with generalized adenovirus infections]. Morphometric, histological, and immunofluorescent studies were carried out with adrenal glands of 14 infants dying with generalized adenovirus infection sometimes concurrent with other acute viral respiratory diseases. Nonspecific changes were found: edema of the capsule and stroma, discomplexation of the trabeculae, circulatory disorders, delipoidization, an increase in the content of DNA and RNA in cells of the definitive cortex, resorption of the elements of the fetal cortex. The pattern of changes of morphometric values attests to increased functional activity of the adrenal cortex. The intensity of the observed changes was directly related to the duration of the disease. The results of clinico-morphological analysis confirm the importance of adrenal insufficiency in tanatogenesis in generalized adenovirus infection. In 10 cases epithelial and endothelial cells of the definitive cortex were found to have specific lesions, the so-called adenovirus cells."}
{"id": "PMID:210739", "title": "[Lesion of the thymus gland in infants caused by cytomegalovirus].", "content": "In the autopsy materials of 1972-1976, cytomegaly was diagnosed in 47 infants dying in the first year of life; two of them were found to have cytomegalovirusinvolvement of the thymus. The clinical course of the disease depended on the intensity of pathological lesions in organs and tissues associated with secondary infection. In the thymus, alongside with marked accidental involution, cytomegaloviral metamorphosis of the reticular epithelium and epithelium of Hassal bodies was found. Foci of calcinosis were observed in the parenchyma of the thymus. During the disease hypogammaglobulinemia was observed. A possible role of cytomegalovirus infection in the development of acquired immunodeficiency conditions in infants under one is suggested.", "contents": "[Lesion of the thymus gland in infants caused by cytomegalovirus]. In the autopsy materials of 1972-1976, cytomegaly was diagnosed in 47 infants dying in the first year of life; two of them were found to have cytomegalovirusinvolvement of the thymus. The clinical course of the disease depended on the intensity of pathological lesions in organs and tissues associated with secondary infection. In the thymus, alongside with marked accidental involution, cytomegaloviral metamorphosis of the reticular epithelium and epithelium of Hassal bodies was found. Foci of calcinosis were observed in the parenchyma of the thymus. During the disease hypogammaglobulinemia was observed. A possible role of cytomegalovirus infection in the development of acquired immunodeficiency conditions in infants under one is suggested."}
{"id": "PMID:210740", "title": "Conduction studies of the saphenous nerve in healthy subjects.", "content": "An easily performed and reproducible method is described for the antidromic determination of conduction velocity in the saphenous nerve. Eighty nerves were studied in 40 healthy subjects and the mean values obtained were as follows: latency 3.6 +/- 0.4 msec, conduction velocity 41.7 +/- 3.4 m/sec, amplitude 9.0 muV. This new technique should be useful in the electrodiagnostic evaluation of peripheral neuropathy, femoral neuropathy and saphenous nerve entrapment syndrome.", "contents": "Conduction studies of the saphenous nerve in healthy subjects. An easily performed and reproducible method is described for the antidromic determination of conduction velocity in the saphenous nerve. Eighty nerves were studied in 40 healthy subjects and the mean values obtained were as follows: latency 3.6 +/- 0.4 msec, conduction velocity 41.7 +/- 3.4 m/sec, amplitude 9.0 muV. This new technique should be useful in the electrodiagnostic evaluation of peripheral neuropathy, femoral neuropathy and saphenous nerve entrapment syndrome."}
{"id": "PMID:210741", "title": "[Ultrastructure of intracellular storage materials in an autopsy case of adult-onset metachromatic leucodystrophy (MLD) (author's transl)].", "content": "Formalin-fixed samples from the demyelinated frontal white matter of an autopsy case of adult-onset MLD were studied by electron microscopy. The intracellular storage materials exhibited the following types of structural patterns: (I) ordinary myelin figures; (II) pleated myelin figures; (III) narrow stacks of lamellar discs which were most likely components of formerly compact \"prismatic\" inclusions; (IV) paired lamellae, either arranged in loose parallel arrays or scattered about in random directions; (V) piles of parallel lamellae with alternating electron-dense and electron-lucent inter-spaces; and (VI) collections of structures resembling fragments of so-called pentalaminar membranes. Types I to IV have already been described in early-onset as well as late-onset forms of MLD, but types V and VI have not. Postmortem autolysis had possibly altered the structural organization of some cytoplasmic deposits and given rise to the formation of those lamellar patterns which were hitherto not known to occur in MLD.", "contents": "[Ultrastructure of intracellular storage materials in an autopsy case of adult-onset metachromatic leucodystrophy (MLD) (author's transl)]. Formalin-fixed samples from the demyelinated frontal white matter of an autopsy case of adult-onset MLD were studied by electron microscopy. The intracellular storage materials exhibited the following types of structural patterns: (I) ordinary myelin figures; (II) pleated myelin figures; (III) narrow stacks of lamellar discs which were most likely components of formerly compact \"prismatic\" inclusions; (IV) paired lamellae, either arranged in loose parallel arrays or scattered about in random directions; (V) piles of parallel lamellae with alternating electron-dense and electron-lucent inter-spaces; and (VI) collections of structures resembling fragments of so-called pentalaminar membranes. Types I to IV have already been described in early-onset as well as late-onset forms of MLD, but types V and VI have not. Postmortem autolysis had possibly altered the structural organization of some cytoplasmic deposits and given rise to the formation of those lamellar patterns which were hitherto not known to occur in MLD."}
{"id": "PMID:210743", "title": "The occurrence of human wart-virus antibodies in dogs, pigs and cattle.", "content": "Using the immunodiffusion method, antibodies against human wart-virus were detected in dog, pig and cattle sera but not in horse and reindeer sera. Antibodies were found in 25 percent (28/114) of the dog sera, the prevalence of antibodies being fairly similar to that in children of the same age. By electron microscopy the antibodies in dog sera were shown to attach to and precipitate the human wart-virus particles, and in immunodiffusion the precipitation lines of human and dog sera were shown to be identical. Of the cattle sera studied, 10 percent (10/97) and of the pig sera 13 percent (5/40) gave a faint precipitation line, having identity with that given by the human sera, against human wart-virus. Conversely 18 percent (9/50) of adult human sera contained precipitating antibodies against a bovine papilloma antigen, probably bovine papilloma virus.", "contents": "The occurrence of human wart-virus antibodies in dogs, pigs and cattle. Using the immunodiffusion method, antibodies against human wart-virus were detected in dog, pig and cattle sera but not in horse and reindeer sera. Antibodies were found in 25 percent (28/114) of the dog sera, the prevalence of antibodies being fairly similar to that in children of the same age. By electron microscopy the antibodies in dog sera were shown to attach to and precipitate the human wart-virus particles, and in immunodiffusion the precipitation lines of human and dog sera were shown to be identical. Of the cattle sera studied, 10 percent (10/97) and of the pig sera 13 percent (5/40) gave a faint precipitation line, having identity with that given by the human sera, against human wart-virus. Conversely 18 percent (9/50) of adult human sera contained precipitating antibodies against a bovine papilloma antigen, probably bovine papilloma virus."}
{"id": "PMID:210744", "title": "The detection of antibody to virus-infection associated (VIA) antigen in various species of African wildlife following natural and experimental infection with foot and mouth disease virus.", "content": "The double immuno-diffusion (DID) test has been applied to detect antibody to VIA antigen in sera from various species of African wild ungulates. In conjunction with the serum neutralisation (SN) test it can be used to decide the degree of risk of movement of animals to other countries free from foot and mouth disease (FMD). The value of the test in assessing the history of infection is limited by its relatively low sensitivity and specificity in respect of virus type.", "contents": "The detection of antibody to virus-infection associated (VIA) antigen in various species of African wildlife following natural and experimental infection with foot and mouth disease virus. The double immuno-diffusion (DID) test has been applied to detect antibody to VIA antigen in sera from various species of African wild ungulates. In conjunction with the serum neutralisation (SN) test it can be used to decide the degree of risk of movement of animals to other countries free from foot and mouth disease (FMD). The value of the test in assessing the history of infection is limited by its relatively low sensitivity and specificity in respect of virus type."}
{"id": "PMID:210745", "title": "T-antigen expression in human skin fibroblasts is not regulated by an endogenous interferon response to SV40 infection.", "content": "Exogenous interferon may affect SV40 T-antigen expression, depending on the chromosomal complement, time of treatment, and biological factors in human cells. However, no evidence was found for endogenous interferon response to SV40 infection in the regulation of T-antigen expression.", "contents": "T-antigen expression in human skin fibroblasts is not regulated by an endogenous interferon response to SV40 infection. Exogenous interferon may affect SV40 T-antigen expression, depending on the chromosomal complement, time of treatment, and biological factors in human cells. However, no evidence was found for endogenous interferon response to SV40 infection in the regulation of T-antigen expression."}
{"id": "PMID:210746", "title": "[Concomitant meningioma and glioblastoma. Report of a case].", "content": "A case of coincidental glioblastoma and meningioma in which the first manifestation were focal convulsive fits is reported. As the association of intracranial tumors is infrequent, their clinical ways of presentation and the theories on their origin are discussed, as well as the importance of the preoperative diagnosis for the surgical planning and prognosis.", "contents": "[Concomitant meningioma and glioblastoma. Report of a case]. A case of coincidental glioblastoma and meningioma in which the first manifestation were focal convulsive fits is reported. As the association of intracranial tumors is infrequent, their clinical ways of presentation and the theories on their origin are discussed, as well as the importance of the preoperative diagnosis for the surgical planning and prognosis."}
{"id": "PMID:210742", "title": "[Local cellular and tributary lymphocyte immunity in cancer of the breast. Diagnostic and prognostic evaluations].", "content": "Following a review of the literature on breast cancer and local and lymph gland immunoreactive state, the results of histomorphological study on a series of 150 cases of breast and axillary lymphnode cancer with and without metastasis, are reported. On the basis of findings, stress is laid on the importance of a more specific assessment of the histomorphological picture (degree of malignity) and the local and tributary lymph node immuno-reactive condition in the interest of a more specific prognostic evaluation.", "contents": "[Local cellular and tributary lymphocyte immunity in cancer of the breast. Diagnostic and prognostic evaluations]. Following a review of the literature on breast cancer and local and lymph gland immunoreactive state, the results of histomorphological study on a series of 150 cases of breast and axillary lymphnode cancer with and without metastasis, are reported. On the basis of findings, stress is laid on the importance of a more specific assessment of the histomorphological picture (degree of malignity) and the local and tributary lymph node immuno-reactive condition in the interest of a more specific prognostic evaluation."}
{"id": "PMID:210747", "title": "Polyneuropathy and folate deficiency.", "content": "We studied five patients (two men and three women, age between 58 and 76 years) with clinical and electrophysiological signs of polyneuropathy. Routine neurological, hematological, and gastroenterological studies as well as procedures to test fat malabsorption were performed. Folate determinations were done using both radioactive and Lactobacillus casei methods. Two patients displayed the signs of subacute combined degeneration of the spinal cord with polyneuropathy, while three had only signs of neuropathy. All had low serum folate concentration, long-standing gastrointestinal disease, and deficient folate intake. The D-xylose absorption test gave values in all patients, while none displayed the classical malabsorption syndrome. The patients had substantial improvement or recovered (according to clinical and electrophysiological measurements) after periods ranging from 9 to 39 months of folate therapy. Such acquired folate-responsive polyneuropathy has two principal characteristics: mixed sensorimotor with mainly sensory deficits, and involvement of one or both of the lower extremities much more extensively than the upper extremities.", "contents": "Polyneuropathy and folate deficiency. We studied five patients (two men and three women, age between 58 and 76 years) with clinical and electrophysiological signs of polyneuropathy. Routine neurological, hematological, and gastroenterological studies as well as procedures to test fat malabsorption were performed. Folate determinations were done using both radioactive and Lactobacillus casei methods. Two patients displayed the signs of subacute combined degeneration of the spinal cord with polyneuropathy, while three had only signs of neuropathy. All had low serum folate concentration, long-standing gastrointestinal disease, and deficient folate intake. The D-xylose absorption test gave values in all patients, while none displayed the classical malabsorption syndrome. The patients had substantial improvement or recovered (according to clinical and electrophysiological measurements) after periods ranging from 9 to 39 months of folate therapy. Such acquired folate-responsive polyneuropathy has two principal characteristics: mixed sensorimotor with mainly sensory deficits, and involvement of one or both of the lower extremities much more extensively than the upper extremities."}
{"id": "PMID:210748", "title": "Decreased spinal cord cGMP in murine (wobbler) spontaneous lower motor neuron degeneration.", "content": "Of the secondary messengers, cyclic quanosine monophosphate, but not cyclic adenosine monophosphate, was reduced by 80% in the cervical spinal cord and by 56% in the cerebellum of clinically affected homozygote \"wobbler\" mice compared to sex- and age-matched litter-mate clinically unaffected control mice. A neurotransmitter, gamma aminobutyric acid, and high-energy intermediates, adenosine triphosphate and phosphocreatine, were not significantly different in affected or unaffected mice.", "contents": "Decreased spinal cord cGMP in murine (wobbler) spontaneous lower motor neuron degeneration. Of the secondary messengers, cyclic quanosine monophosphate, but not cyclic adenosine monophosphate, was reduced by 80% in the cervical spinal cord and by 56% in the cerebellum of clinically affected homozygote \"wobbler\" mice compared to sex- and age-matched litter-mate clinically unaffected control mice. A neurotransmitter, gamma aminobutyric acid, and high-energy intermediates, adenosine triphosphate and phosphocreatine, were not significantly different in affected or unaffected mice."}
{"id": "PMID:210749", "title": "Malignant salivary gland tumors of the palate.", "content": "Twenty patients with malignant salivary gland tumors of the hard and soft palate were seen at the University of Virginia Hospital from 1956 through 1975. The characteristics of the tumors, including symptoms and histology are reviewed and the results of treatment are analyzed. In particular, the place of radiotherapy in their management has been examined. Primary control by initial surgery alone was achieved in 60% (9/15) of the cases, and, when those patients who received radiotherapy for residual disease or salvage are included, the primary control was 94% (16/17). Five- and ten-year determinate survival rates were 88% and 67%, respectively. From this retrospective analysis and a review of the literature, it appears that radiotherapy has made a very positive contribution to the management of these tumors.", "contents": "Malignant salivary gland tumors of the palate. Twenty patients with malignant salivary gland tumors of the hard and soft palate were seen at the University of Virginia Hospital from 1956 through 1975. The characteristics of the tumors, including symptoms and histology are reviewed and the results of treatment are analyzed. In particular, the place of radiotherapy in their management has been examined. Primary control by initial surgery alone was achieved in 60% (9/15) of the cases, and, when those patients who received radiotherapy for residual disease or salvage are included, the primary control was 94% (16/17). Five- and ten-year determinate survival rates were 88% and 67%, respectively. From this retrospective analysis and a review of the literature, it appears that radiotherapy has made a very positive contribution to the management of these tumors."}
{"id": "PMID:210751", "title": "Perinatal foal mortality associated with a herpesvirus.", "content": "An outbreak of perinatal foal mortality associated with a herpesvirus is described. Twenty two foals either were still-born, or died soon after birth, or were weak and soon developed severe respiratory signs, or were normal at birth and developed respiratory symptoms 18 to 24 hours later. Elevated temperatures, heart and respiratory rates were constant features. The animals were severely leucopaenic, and showed an absolute neutropaenia. At autopsy the lungs were enlarged, and showed varying degrees of aeration and moderate to severe oedema and congestion. Histopathology showed an acute focal necrotising bronchiolitis with the presence of intranuclear eosinophilic inclusion bodies. Herpesvirus was recovered from 9 foals in cell culture and identified by electron microscopy.", "contents": "Perinatal foal mortality associated with a herpesvirus. An outbreak of perinatal foal mortality associated with a herpesvirus is described. Twenty two foals either were still-born, or died soon after birth, or were weak and soon developed severe respiratory signs, or were normal at birth and developed respiratory symptoms 18 to 24 hours later. Elevated temperatures, heart and respiratory rates were constant features. The animals were severely leucopaenic, and showed an absolute neutropaenia. At autopsy the lungs were enlarged, and showed varying degrees of aeration and moderate to severe oedema and congestion. Histopathology showed an acute focal necrotising bronchiolitis with the presence of intranuclear eosinophilic inclusion bodies. Herpesvirus was recovered from 9 foals in cell culture and identified by electron microscopy."}
{"id": "PMID:210755", "title": "Diarrhoea in piglets inoculated with rotavirus.", "content": "A rotavirus isolated from a field outbreak of diarrhoea in artificially reared piglets was purified, filtered and administered orally to gnotobiotic and conventional piglets. Four successive passages of the virus in gnotobiotic piglets produced severe diarrhoea within 20 to 24 hours of administration. The diarrhoea lasted several days causing dehydration, emaciation, loss of body weight and some deaths. Virus was demonstrated in the faeces of the infected piglets by electron microscopy. Conventionally reared piglets developed little or no diarrhoea when given virus, whereas artificially reared piglets developed moderate to severe diarrhoea which lasted from 3 to 8 days with some deaths. No clinical disease was obvious in surviving piglets following challenge with the virus 10 or 17 days after initial infections.", "contents": "Diarrhoea in piglets inoculated with rotavirus. A rotavirus isolated from a field outbreak of diarrhoea in artificially reared piglets was purified, filtered and administered orally to gnotobiotic and conventional piglets. Four successive passages of the virus in gnotobiotic piglets produced severe diarrhoea within 20 to 24 hours of administration. The diarrhoea lasted several days causing dehydration, emaciation, loss of body weight and some deaths. Virus was demonstrated in the faeces of the infected piglets by electron microscopy. Conventionally reared piglets developed little or no diarrhoea when given virus, whereas artificially reared piglets developed moderate to severe diarrhoea which lasted from 3 to 8 days with some deaths. No clinical disease was obvious in surviving piglets following challenge with the virus 10 or 17 days after initial infections."}
{"id": "PMID:210756", "title": "Spinal cord compression caused by a metastatic lesion from an aortic body tumour.", "content": "An aortic body tumour in a 7-year-old wire-haired fox terrier with hind limb ataxia is described. A metastatic lesion in the dorsal arch of the eighth thoracic vertebra caused compression of the spinal cord. Radiographic techniques are discussed that enabled the position and extent of the primary tumour and its metastasis to be defined and allowed a provisional diagnosis of chemodectoma.", "contents": "Spinal cord compression caused by a metastatic lesion from an aortic body tumour. An aortic body tumour in a 7-year-old wire-haired fox terrier with hind limb ataxia is described. A metastatic lesion in the dorsal arch of the eighth thoracic vertebra caused compression of the spinal cord. Radiographic techniques are discussed that enabled the position and extent of the primary tumour and its metastasis to be defined and allowed a provisional diagnosis of chemodectoma."}
{"id": "PMID:210759", "title": "Stimulation of the respiratory chain of rat liver mitochondria between cytochrome c1 and cytochrome c by glucagon treatment of rats.", "content": "Mitochondria from glucagon-treated rats oxidize succinate, but not ascorbate plus tetramethylphenylenediamine, faster in the uncoupled state than do control mitochondria. The rate of O(2) uptake in the presence of both substrates is equal to the sum of the rates of the O(2) uptake in the presence of either substrate alone. It is concluded that the mitochondrial respiratory chain is limited at some point between cytochromes b and c and that this step is regulated by glucagon. Measurement of the cytochrome spectra under uncoupled conditions in the presence of succinate and rotenone demonstrates a crossover between cytochromes c and c(1) when control mitochondria are compared with those from glucagon-treated rats, cytochrome c being more oxidized and cytochrome c(1) more reduced in control mitochondria. Under conditions where pyruvate metabolism is studied the control mitochondria are generally more oxidized than those from glucagon-treated rats, the redox state of cytochrome b-566 correlating with the rate of pyruvate metabolism in sucrose medium. However, when the redox state of the mitochondria is taken into account, a crossover between cytochromes c and c(1) is again apparent. The spectra of the b cytochromes are complex, but cytochrome b-562 appears to become more reduced relative to cytochrome b-566 in mitochondria from glucagon-treated rats than in control mitochondria. This can be explained by the existence of a more alkaline matrix in glucagon-treated rats, the redox potential for cytochrome b being pH-sensitive. It is concluded that glucagon stimulates electron flow between cytochromes c(1) and c. The physiological significance of these findings is discussed.", "contents": "Stimulation of the respiratory chain of rat liver mitochondria between cytochrome c1 and cytochrome c by glucagon treatment of rats. Mitochondria from glucagon-treated rats oxidize succinate, but not ascorbate plus tetramethylphenylenediamine, faster in the uncoupled state than do control mitochondria. The rate of O(2) uptake in the presence of both substrates is equal to the sum of the rates of the O(2) uptake in the presence of either substrate alone. It is concluded that the mitochondrial respiratory chain is limited at some point between cytochromes b and c and that this step is regulated by glucagon. Measurement of the cytochrome spectra under uncoupled conditions in the presence of succinate and rotenone demonstrates a crossover between cytochromes c and c(1) when control mitochondria are compared with those from glucagon-treated rats, cytochrome c being more oxidized and cytochrome c(1) more reduced in control mitochondria. Under conditions where pyruvate metabolism is studied the control mitochondria are generally more oxidized than those from glucagon-treated rats, the redox state of cytochrome b-566 correlating with the rate of pyruvate metabolism in sucrose medium. However, when the redox state of the mitochondria is taken into account, a crossover between cytochromes c and c(1) is again apparent. The spectra of the b cytochromes are complex, but cytochrome b-562 appears to become more reduced relative to cytochrome b-566 in mitochondria from glucagon-treated rats than in control mitochondria. This can be explained by the existence of a more alkaline matrix in glucagon-treated rats, the redox potential for cytochrome b being pH-sensitive. It is concluded that glucagon stimulates electron flow between cytochromes c(1) and c. The physiological significance of these findings is discussed."}
{"id": "PMID:210760", "title": "Adenosine 3':5'-cyclic monophosphate-dependent protein kinase(s) of rat ovarian cells. Gonadotropin regulation of adenosine 3':5'-cyclic monophosphate-receptor activity.", "content": "Regulation of cyclic AMP-dependent protein kinase, cyclic AMP-receptor activity and intracellular cyclic AMP concentrations by choriogonadotropin was studied in ovarian cells prepared from 26-day-old rats. A close correlation was observed between phospho-transferase activity and cyclic AMP-receptor activity in 12000g supernatant fractions from rat ovarian homogenate. The apparent activation constant (K(a)) and I(50) (concentration required to produce 50% inhibition) of different cyclic nucleotides for phosphotransferase and cyclic AMP receptor activities respectively were also determined. Cyclic AMP and 8-bromo cyclic AMP were most effective, giving K(a) values of 0.08 and 0.09mum and I(50) of 0.12 and 0.16mum respectively. Other nucleotides were also effective, but required higher concentrations to give a comparable effect. An increased concentration of cyclic AMP produced by choriogonadotropin (1mug/ml) treatment was accompanied by decreased cyclic AMP binding as early as 5min after hormone addition. Choriogonadotropin also stimulated the protein kinase activity ratio (-cyclic AMP/+cyclic AMP) under identical experimental conditions. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine potentiated the action of choriogonadotropin on the three parameters measured in a dose- and time-dependent manner. The maximal cyclic AMP-binding capacity, as determined by cyclic AMP-exchange assay, remained unchanged before and after hormone addition. The endogenously bound cyclic AMP was determined from the difference between the maximal binding capacity and the exogenously bound cyclic AMP. With different choriogonadotropin concentrations, a quantitative correlation was established between maximal binding capacity, exogenous binding and endogenous binding activities. Approx. 60% of total binding sites were endogenously occupied in untreated cells, and choriogonadotropin (1mug/ml) treatment fully saturated available binding sites with a parallel 10-fold increase in cellular cyclic AMP. The present results provide evidence for a probable intracellular compartmentalization of cyclic AMP in the ovarian cell, and suggest that in the unstimulated state all cyclic AMP present in the ovarian cell may not be available for protein kinase activation.", "contents": "Adenosine 3':5'-cyclic monophosphate-dependent protein kinase(s) of rat ovarian cells. Gonadotropin regulation of adenosine 3':5'-cyclic monophosphate-receptor activity. Regulation of cyclic AMP-dependent protein kinase, cyclic AMP-receptor activity and intracellular cyclic AMP concentrations by choriogonadotropin was studied in ovarian cells prepared from 26-day-old rats. A close correlation was observed between phospho-transferase activity and cyclic AMP-receptor activity in 12000g supernatant fractions from rat ovarian homogenate. The apparent activation constant (K(a)) and I(50) (concentration required to produce 50% inhibition) of different cyclic nucleotides for phosphotransferase and cyclic AMP receptor activities respectively were also determined. Cyclic AMP and 8-bromo cyclic AMP were most effective, giving K(a) values of 0.08 and 0.09mum and I(50) of 0.12 and 0.16mum respectively. Other nucleotides were also effective, but required higher concentrations to give a comparable effect. An increased concentration of cyclic AMP produced by choriogonadotropin (1mug/ml) treatment was accompanied by decreased cyclic AMP binding as early as 5min after hormone addition. Choriogonadotropin also stimulated the protein kinase activity ratio (-cyclic AMP/+cyclic AMP) under identical experimental conditions. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine potentiated the action of choriogonadotropin on the three parameters measured in a dose- and time-dependent manner. The maximal cyclic AMP-binding capacity, as determined by cyclic AMP-exchange assay, remained unchanged before and after hormone addition. The endogenously bound cyclic AMP was determined from the difference between the maximal binding capacity and the exogenously bound cyclic AMP. With different choriogonadotropin concentrations, a quantitative correlation was established between maximal binding capacity, exogenous binding and endogenous binding activities. Approx. 60% of total binding sites were endogenously occupied in untreated cells, and choriogonadotropin (1mug/ml) treatment fully saturated available binding sites with a parallel 10-fold increase in cellular cyclic AMP. The present results provide evidence for a probable intracellular compartmentalization of cyclic AMP in the ovarian cell, and suggest that in the unstimulated state all cyclic AMP present in the ovarian cell may not be available for protein kinase activation."}
{"id": "PMID:210761", "title": "The role of creatine kinase and arginine kinase in muscle.", "content": "Arginine and creatine kinase activities in different muscles are compared with calculated maximum rates of ATP turnover. The magnitude of the kinase activities decreases in the following order: anaerobic muscles and vertebrate skeletal muscles greater than heart muscle greater than insect flight muscle. The maximum activity of phosphagen kinases (i.e. creatine kinase and arginine kinase), in the direction of phosphagen formation, is lower than the calculated maximum rate of ATP turnover in insect flight muscle or rat heart.", "contents": "The role of creatine kinase and arginine kinase in muscle. Arginine and creatine kinase activities in different muscles are compared with calculated maximum rates of ATP turnover. The magnitude of the kinase activities decreases in the following order: anaerobic muscles and vertebrate skeletal muscles greater than heart muscle greater than insect flight muscle. The maximum activity of phosphagen kinases (i.e. creatine kinase and arginine kinase), in the direction of phosphagen formation, is lower than the calculated maximum rate of ATP turnover in insect flight muscle or rat heart."}
{"id": "PMID:210762", "title": "The role of phospholipids in the reduction of ubiquinone analogues by the mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase complex.", "content": "The isolated NADH-ubiquinone oxidoreductase complex of bovine heart mitochondria reduces ubiquinone analogues by two pathways. One pathway is inhibited by rotenone, and reduction of quinones takes place in the lipid phase of the system. The other pathway is insensitive to rotenone and reduction takes place in the aqueous phase. The variation of rates of electron transpport with the chemical nature of the quinone analogue and the concentrations of both quinone and phospholipid can be rationalized in terms of partition of the quinone between the aqueous and lipid phases of the system. Thus one function of phospholipid associated with the enzyme appears to be to act as solvent for ubiquinone reduced by the rotenone-sensitive pathway. This proposal is supported by the kinetic behaviour of enzyme whose endogenous lipids have been replaced by (1,2)-dimyristoylsn-glycero-3-phosphocholine. Thus, under certain circumstances, the rotenone-sensitive reduction of ubiquinone-1 exhibited a substantial increase in activation energy below the phase-transition temperature of the synthetic lipid, whereas the reduction of other acceptors was unaffected.", "contents": "The role of phospholipids in the reduction of ubiquinone analogues by the mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase complex. The isolated NADH-ubiquinone oxidoreductase complex of bovine heart mitochondria reduces ubiquinone analogues by two pathways. One pathway is inhibited by rotenone, and reduction of quinones takes place in the lipid phase of the system. The other pathway is insensitive to rotenone and reduction takes place in the aqueous phase. The variation of rates of electron transpport with the chemical nature of the quinone analogue and the concentrations of both quinone and phospholipid can be rationalized in terms of partition of the quinone between the aqueous and lipid phases of the system. Thus one function of phospholipid associated with the enzyme appears to be to act as solvent for ubiquinone reduced by the rotenone-sensitive pathway. This proposal is supported by the kinetic behaviour of enzyme whose endogenous lipids have been replaced by (1,2)-dimyristoylsn-glycero-3-phosphocholine. Thus, under certain circumstances, the rotenone-sensitive reduction of ubiquinone-1 exhibited a substantial increase in activation energy below the phase-transition temperature of the synthetic lipid, whereas the reduction of other acceptors was unaffected."}
{"id": "PMID:210763", "title": "Effects of hormones and N6O2'-dibutyryl-adenosine 3' :5'-cyclic monophosphate, administered in vivo, on phosphate transport and metabolism in isolated rat liver mitochondria.", "content": "1. The administration of glucagon or N6O2'-dibutyryl cyclic AMP to fed rats by intraperitoneal injection was associated with a 2-fold increase in the amounts of endogenous Pi and ATP, and an increase in the rate and extent of transport of exogenous Pi (measured in either the presence or the absence of Ca2+) in mitochondria subsequently isolated from the liver. No change was observed in either the maximum rate of transport of exogenous Pi or in the rate of 32Pi exchange. 2. The changes induced by glucagon and dibutyryl cyclic AMP were markedly decreased by the co-administration of cycloheximide. 3. The administration of insulin to rats resulted in an increase of about 1.3-fold in the concentration of endogenous mitochondrial Pi 4. The amounts of endogenous Pi in mitochondrial isolated from the livers of starved rats were 3 times those in mitochondria isolated from fed animals. 5. It is concluded that the liver mitochondrial phosphatetransport system may be an important site of hormone action. 6. In the course of these experiments, it was shown that Ca2+ markedly stimulates mitochondrial phosphate transports.", "contents": "Effects of hormones and N6O2'-dibutyryl-adenosine 3' :5'-cyclic monophosphate, administered in vivo, on phosphate transport and metabolism in isolated rat liver mitochondria. 1. The administration of glucagon or N6O2'-dibutyryl cyclic AMP to fed rats by intraperitoneal injection was associated with a 2-fold increase in the amounts of endogenous Pi and ATP, and an increase in the rate and extent of transport of exogenous Pi (measured in either the presence or the absence of Ca2+) in mitochondria subsequently isolated from the liver. No change was observed in either the maximum rate of transport of exogenous Pi or in the rate of 32Pi exchange. 2. The changes induced by glucagon and dibutyryl cyclic AMP were markedly decreased by the co-administration of cycloheximide. 3. The administration of insulin to rats resulted in an increase of about 1.3-fold in the concentration of endogenous mitochondrial Pi 4. The amounts of endogenous Pi in mitochondrial isolated from the livers of starved rats were 3 times those in mitochondria isolated from fed animals. 5. It is concluded that the liver mitochondrial phosphatetransport system may be an important site of hormone action. 6. In the course of these experiments, it was shown that Ca2+ markedly stimulates mitochondrial phosphate transports."}
{"id": "PMID:210764", "title": "The reaction of Pseudomonas aeruginosa cytochrome c-551 oxidase with oxygen.", "content": "The reaction of ascorbate-reduced Pseudomonas cytochrome oxidase with oxygen was studied by using stopped-flow techniques at pH 7.0 and 25 degrees C. The observed time courses were complex, the reaction consisting of three phases. Of these, only the fastest process, with a second-order rate constant of 3.3 X 10(4) M-1.S-1, was dependent on oxygen concentration. The two slower processes were first-order reactions with rates of 1.0 +/- 0.4s-1 and 0.1 +/- 0.03s-1. A kinetic titration experiment revealed that the enzyme had a relatively low affinity constant for oxygen, approx. 10(4)M-1. Kinetic difference spectra were determined for all three reaction phases, showing each to have different characteristics. The fast-phase difference spectrum showed that changes occurred at both the haem c and haem d1 components of the enzyme during this process. These changes were consistent with the haem c becoming oxidized, but with the haem d1 assuming a form that did not correspond to the normal oxidized state, a situation that was not restored even after the second kinetic phase, which reflected further changes in the haem d1 component. The results are discussed in terms of a kinetic scheme.", "contents": "The reaction of Pseudomonas aeruginosa cytochrome c-551 oxidase with oxygen. The reaction of ascorbate-reduced Pseudomonas cytochrome oxidase with oxygen was studied by using stopped-flow techniques at pH 7.0 and 25 degrees C. The observed time courses were complex, the reaction consisting of three phases. Of these, only the fastest process, with a second-order rate constant of 3.3 X 10(4) M-1.S-1, was dependent on oxygen concentration. The two slower processes were first-order reactions with rates of 1.0 +/- 0.4s-1 and 0.1 +/- 0.03s-1. A kinetic titration experiment revealed that the enzyme had a relatively low affinity constant for oxygen, approx. 10(4)M-1. Kinetic difference spectra were determined for all three reaction phases, showing each to have different characteristics. The fast-phase difference spectrum showed that changes occurred at both the haem c and haem d1 components of the enzyme during this process. These changes were consistent with the haem c becoming oxidized, but with the haem d1 assuming a form that did not correspond to the normal oxidized state, a situation that was not restored even after the second kinetic phase, which reflected further changes in the haem d1 component. The results are discussed in terms of a kinetic scheme."}
{"id": "PMID:210765", "title": "Mechanism of oxyhaemoglobin breakdown on reaction with acetylphenylhydrazine.", "content": "The reaction of oxyhaemoglobin and acetylphenylhydrazine, which results in haemoglobin denaturation and precipitation, was found to be influenced by H202 and superoxide (O2-.) generated during the reaction. By analysing the different haemoglobin oxidation products, it was found that by influencing the rate at which oxyhaemoglobin was oxidized, H2O2 accelerated the overall haemoglobin breakdown, and O2-. inhibited it. By adding GSH (reduced glutathione) or ascorbate, it was possible to slow down the rates of both oxyhaemoglobin oxidation and O2-. production, and the overall rate of haemoglobin breakdown. These results are compatible with a mechanism involving production of the acetylphenylhydrazyl free radical, and with GSH, ascorbate and O2-. acting as radical scavengers and preventing its further reactions. The reaction produced choleglobin, as well as acetylphenyldiazine and methaemoglobin, which combined to form a haemichrome. The haemichrome was less stable and precipitated first. It was also less stable than the haemichrome formed by direct reaction of acetylphenyldiazine with methaemoglobin, and it is proposed that this is because the methaemoglobin produced from oxyhaemoglobin and acetylphenylhydrazine was modified by the free radicals and H2O2 produced in the reaction.", "contents": "Mechanism of oxyhaemoglobin breakdown on reaction with acetylphenylhydrazine. The reaction of oxyhaemoglobin and acetylphenylhydrazine, which results in haemoglobin denaturation and precipitation, was found to be influenced by H202 and superoxide (O2-.) generated during the reaction. By analysing the different haemoglobin oxidation products, it was found that by influencing the rate at which oxyhaemoglobin was oxidized, H2O2 accelerated the overall haemoglobin breakdown, and O2-. inhibited it. By adding GSH (reduced glutathione) or ascorbate, it was possible to slow down the rates of both oxyhaemoglobin oxidation and O2-. production, and the overall rate of haemoglobin breakdown. These results are compatible with a mechanism involving production of the acetylphenylhydrazyl free radical, and with GSH, ascorbate and O2-. acting as radical scavengers and preventing its further reactions. The reaction produced choleglobin, as well as acetylphenyldiazine and methaemoglobin, which combined to form a haemichrome. The haemichrome was less stable and precipitated first. It was also less stable than the haemichrome formed by direct reaction of acetylphenyldiazine with methaemoglobin, and it is proposed that this is because the methaemoglobin produced from oxyhaemoglobin and acetylphenylhydrazine was modified by the free radicals and H2O2 produced in the reaction."}
{"id": "PMID:210766", "title": "Electron-paramagnetic-resonance studies on nitrogenase of Klebsiella pneumoniae. Evidence for acetylene- and ethylene-nitrogenase transient complexes.", "content": "Klebsiella pneumoniae nitrogenase exhibited four new electron-paramagnetic-resonance signals during turnover at 10 degrees C, pH7.4, which were assigned to intermediates present in low concentrations in the steady state. 57Fe-substituted Mo--Fe protein showed that they arose from Fe--S clusters in the Mo--Fe protein of nitrogenase. The new signals are designated: Ic, g values at 4.67, 3.37 and approx. 2.0; VI, g values at 2.125, 2.000 and 2.000; VII, g values at 5.7 and 5.4; VIII, g values at 2.092, 1.974 and 1.933. The sharp axial signal VI arises from a Fe4S4 cluster at the --1 oxidation level. This signal was only detected in the presence of ethylene and provides the first evidence of an enzyme--product complex for nitrogenase. [13C]Acetylene and [13C]ethylene provided no evidence for direct binding of this substrate and product to the Fe--S clusters giving rise to these signals. The dependence of signal intensities on acetylene concentration indicated two types of binding site, with apparent dissociation constants K less than 16 micron and K approximately 13mM. A single binding site for ethylene (K=1.5mM) was detected. A scheme is proposed for the mechanism of reduction of acetylene to ethylene and inhibition of this reaction by CO.", "contents": "Electron-paramagnetic-resonance studies on nitrogenase of Klebsiella pneumoniae. Evidence for acetylene- and ethylene-nitrogenase transient complexes. Klebsiella pneumoniae nitrogenase exhibited four new electron-paramagnetic-resonance signals during turnover at 10 degrees C, pH7.4, which were assigned to intermediates present in low concentrations in the steady state. 57Fe-substituted Mo--Fe protein showed that they arose from Fe--S clusters in the Mo--Fe protein of nitrogenase. The new signals are designated: Ic, g values at 4.67, 3.37 and approx. 2.0; VI, g values at 2.125, 2.000 and 2.000; VII, g values at 5.7 and 5.4; VIII, g values at 2.092, 1.974 and 1.933. The sharp axial signal VI arises from a Fe4S4 cluster at the --1 oxidation level. This signal was only detected in the presence of ethylene and provides the first evidence of an enzyme--product complex for nitrogenase. [13C]Acetylene and [13C]ethylene provided no evidence for direct binding of this substrate and product to the Fe--S clusters giving rise to these signals. The dependence of signal intensities on acetylene concentration indicated two types of binding site, with apparent dissociation constants K less than 16 micron and K approximately 13mM. A single binding site for ethylene (K=1.5mM) was detected. A scheme is proposed for the mechanism of reduction of acetylene to ethylene and inhibition of this reaction by CO."}
{"id": "PMID:210767", "title": "Studies on the time course and rate-limiting steps in the activation of adenylate cyclase in rat liver by cholera toxin.", "content": "Cholera toxin stimulates adenylate cyclase in rat liver after intravenous injection. The stimulation follows a short latent period of 10min, and maximum stimulation was attained at 120min. Half-maximal stimulation was achieved at 35min. In contrast with this lengthy time course in the intact cell, adenylate cyclase in broken-cell preparations of rat liver in vitro were maximally stimulated by cholera toxin (in the presence of NAD+) in 20min with half-maximal stimulation in 8min. Binding of cholera toxin to cell membranes by the B subunits is followed by translocation of the A subunit into the cell or cell membrane, and separation of the A1 polypeptide chain from the A2 chain by disulphide-bond reduction, and finally activation of adenylate cyclase by the A1 chain and NAD+. As the binding of cholera toxin is rapid, two possible rate-limiting steps could be the determinants of the long time course of action. These are translocation of the A1 chain from the outside of the cell membrane to its site of action (this includes the time required for separation from the whole toxin) or the availability of NAD+ for activation. When NAD+ concentrations in rat liver were elevated 4-fold, by the administration of nicotinamide, no change in the rate of activation of adenylate cyclase by cholera toxin was observed. Thus the intracellular concentration of NAD+ is not rate-limiting and the major rate-limiting determinant in intact cells must be between the time of toxin binding to the cell membrane and the appearance of subunit A1 at the enzyme site.", "contents": "Studies on the time course and rate-limiting steps in the activation of adenylate cyclase in rat liver by cholera toxin. Cholera toxin stimulates adenylate cyclase in rat liver after intravenous injection. The stimulation follows a short latent period of 10min, and maximum stimulation was attained at 120min. Half-maximal stimulation was achieved at 35min. In contrast with this lengthy time course in the intact cell, adenylate cyclase in broken-cell preparations of rat liver in vitro were maximally stimulated by cholera toxin (in the presence of NAD+) in 20min with half-maximal stimulation in 8min. Binding of cholera toxin to cell membranes by the B subunits is followed by translocation of the A subunit into the cell or cell membrane, and separation of the A1 polypeptide chain from the A2 chain by disulphide-bond reduction, and finally activation of adenylate cyclase by the A1 chain and NAD+. As the binding of cholera toxin is rapid, two possible rate-limiting steps could be the determinants of the long time course of action. These are translocation of the A1 chain from the outside of the cell membrane to its site of action (this includes the time required for separation from the whole toxin) or the availability of NAD+ for activation. When NAD+ concentrations in rat liver were elevated 4-fold, by the administration of nicotinamide, no change in the rate of activation of adenylate cyclase by cholera toxin was observed. Thus the intracellular concentration of NAD+ is not rate-limiting and the major rate-limiting determinant in intact cells must be between the time of toxin binding to the cell membrane and the appearance of subunit A1 at the enzyme site."}
{"id": "PMID:210768", "title": "Binding of ligands and spectral shifts in cytochrome c oxidase.", "content": "1. On addition of reductant (ascorbate plus NNN'N'-tetramethyl-p-phenylenediamine) to isolated cytochrome c oxidase (ox heart cytochrome aa(3)), in the presence of the inhibitors azide or cyanide, an initial partially reduced species is formed with absorption peaks at 415nm, 445nm and 605nm, which slowly gives rise to the final ;half-reduced' species in whose spectrum the 415nm peak has disappeared and a new absorption is seen at 430-435nm. 2. In the absence of reductant, cyanide forms an initial complex with the enzyme with a spectrum similar to that of the uncombined form, which slowly changes into the ;low-spin' cyanide form with a peak at 432nm. Azide, in absence of reductant, shifts the Soret peak slightly, but the resulting complex, which is probably thermally ;mixed-spin', undergoes no further changes. 3. The Soret-peak shift of oxidized cytochrome a(3) which occurs on reduction of the enzyme in the presence of azide is accompanied by a concurrent blue shift of the ferrous cytochrome a peak from 605nm to 603nm. A partial blue shift of the alpha-peak occurs in the half-reduced sulphide-inhibited enzyme, and a complete blue shift is seen in the analogous complexes with alkyl sulphides [a(2+)a(3) (3+)HSR compounds, where R=CH(3), C(2)H(5) or (CH(3))(2)CH]. 4. Analogous, albeit less readily decipherable, spectroscopic effects with the ligands imidazole and alkyl isocyanides suggest that on reduction of cytochrome a an interaction occurs between the two haem groups involving (i) a high- to low-spin change in cytochrome a(3), and after this, (ii) a change in the molecular environment of the cytochrome a. The latter effect, possibly a decrease in the hydrophobicity of the haem pocket, requires that the ligands on cytochrome a(3) have a bulky and partially hydrophobic character.", "contents": "Binding of ligands and spectral shifts in cytochrome c oxidase. 1. On addition of reductant (ascorbate plus NNN'N'-tetramethyl-p-phenylenediamine) to isolated cytochrome c oxidase (ox heart cytochrome aa(3)), in the presence of the inhibitors azide or cyanide, an initial partially reduced species is formed with absorption peaks at 415nm, 445nm and 605nm, which slowly gives rise to the final ;half-reduced' species in whose spectrum the 415nm peak has disappeared and a new absorption is seen at 430-435nm. 2. In the absence of reductant, cyanide forms an initial complex with the enzyme with a spectrum similar to that of the uncombined form, which slowly changes into the ;low-spin' cyanide form with a peak at 432nm. Azide, in absence of reductant, shifts the Soret peak slightly, but the resulting complex, which is probably thermally ;mixed-spin', undergoes no further changes. 3. The Soret-peak shift of oxidized cytochrome a(3) which occurs on reduction of the enzyme in the presence of azide is accompanied by a concurrent blue shift of the ferrous cytochrome a peak from 605nm to 603nm. A partial blue shift of the alpha-peak occurs in the half-reduced sulphide-inhibited enzyme, and a complete blue shift is seen in the analogous complexes with alkyl sulphides [a(2+)a(3) (3+)HSR compounds, where R=CH(3), C(2)H(5) or (CH(3))(2)CH]. 4. Analogous, albeit less readily decipherable, spectroscopic effects with the ligands imidazole and alkyl isocyanides suggest that on reduction of cytochrome a an interaction occurs between the two haem groups involving (i) a high- to low-spin change in cytochrome a(3), and after this, (ii) a change in the molecular environment of the cytochrome a. The latter effect, possibly a decrease in the hydrophobicity of the haem pocket, requires that the ligands on cytochrome a(3) have a bulky and partially hydrophobic character."}
{"id": "PMID:210769", "title": "[Hepatocarcinoma in an 18 month old patient].", "content": "The patient was an 18 month old female showing a mass in the right upper quadrant. At the examination, in epigastrium and right hypochondrium, a soft tumor mass embodied to the liver was felt. The patient was operated after laboratory studies including an hepatogram were done, but without having determined alpha phetoglobulin. A 15 X 15 cms. spherical mass was found forming body with the left lobe of the liver and was removed together with the lobe. The pathological diagnosis was of hepatocarcinoma, according to ishak and Glunz's classification. All this leads to comment how interesting is the determination of serological tests for alpha phetoglobulins as a measure to aid in the diagnosis. Likewise, the surgical management carried out is a determinant measure for the treatment of these tumors. At present, survivals up to 6 years may be offered. The reason why this case is reported is because hepatocarcinoma is very uncommon at this age.", "contents": "[Hepatocarcinoma in an 18 month old patient]. The patient was an 18 month old female showing a mass in the right upper quadrant. At the examination, in epigastrium and right hypochondrium, a soft tumor mass embodied to the liver was felt. The patient was operated after laboratory studies including an hepatogram were done, but without having determined alpha phetoglobulin. A 15 X 15 cms. spherical mass was found forming body with the left lobe of the liver and was removed together with the lobe. The pathological diagnosis was of hepatocarcinoma, according to ishak and Glunz's classification. All this leads to comment how interesting is the determination of serological tests for alpha phetoglobulins as a measure to aid in the diagnosis. Likewise, the surgical management carried out is a determinant measure for the treatment of these tumors. At present, survivals up to 6 years may be offered. The reason why this case is reported is because hepatocarcinoma is very uncommon at this age."}
{"id": "PMID:210774", "title": "Age-dependent changes in the activities of ATPase and some pyridine nucleotide-linked enzymes in the chick testis.", "content": "The ontogeny of some of the enzymes connected with carbohydrate metabolism in the testis were studied in the White-Rock chicks. In the first place testicular growth in these chicks relate to their overall growth as measured by their body weights. ATPase and NAD+-dependent succinic dehydrogenase activities decreased both with advancing age and increasing testicular weight. However, these enzymes showed maximum activities at 17 and 28 weeks respectively. NAD+-linked isocitric dehydrogenase activity continually increased with increasing testicular weight and age. It is suggested that during spermatogenesis the activities of these enzymes are controlled by different developmental mechanisms.", "contents": "Age-dependent changes in the activities of ATPase and some pyridine nucleotide-linked enzymes in the chick testis. The ontogeny of some of the enzymes connected with carbohydrate metabolism in the testis were studied in the White-Rock chicks. In the first place testicular growth in these chicks relate to their overall growth as measured by their body weights. ATPase and NAD+-dependent succinic dehydrogenase activities decreased both with advancing age and increasing testicular weight. However, these enzymes showed maximum activities at 17 and 28 weeks respectively. NAD+-linked isocitric dehydrogenase activity continually increased with increasing testicular weight and age. It is suggested that during spermatogenesis the activities of these enzymes are controlled by different developmental mechanisms."}
{"id": "PMID:210775", "title": "Ca2+-activated ATPase of rat liver plasma membrane.", "content": "Rat liver plasma membranes hydrolyze ATP in the presence of Ca2+. The rate of hydrolysis is different when Mg2+ions are present in the incubation system. Several  parameters differentiate Ca2+-ATPase from Mg2+-ATPase: a) the Km of ATP hydrolysis for Ca2+ (2.25 x 10(-4) M) is lower than for Mg2+ (2.14 x 10(-3) M); b) the shape of the activation curve is hyperbolic in the presence of Ca2+ and sigmoid in the presence of Mg2+; c) Mg2+-ATPase shows two different values of activation energy while Ca2+-ATPase presents only a single value; d) Ca2+-ATPase is inhibited, while Mg2+-ATPase is unaffected by cyclic AMP. Ca2+-ATPase is localized on the plasma membrane and is not inhibited by cysteine. It does not hydrolyze substrates different from nucleotides triphosphate, such as glucose-1-phosphate or alpha-glycero-phosphate. The enzyme is probably related to a mechanism of calcium transport.", "contents": "Ca2+-activated ATPase of rat liver plasma membrane. Rat liver plasma membranes hydrolyze ATP in the presence of Ca2+. The rate of hydrolysis is different when Mg2+ions are present in the incubation system. Several  parameters differentiate Ca2+-ATPase from Mg2+-ATPase: a) the Km of ATP hydrolysis for Ca2+ (2.25 x 10(-4) M) is lower than for Mg2+ (2.14 x 10(-3) M); b) the shape of the activation curve is hyperbolic in the presence of Ca2+ and sigmoid in the presence of Mg2+; c) Mg2+-ATPase shows two different values of activation energy while Ca2+-ATPase presents only a single value; d) Ca2+-ATPase is inhibited, while Mg2+-ATPase is unaffected by cyclic AMP. Ca2+-ATPase is localized on the plasma membrane and is not inhibited by cysteine. It does not hydrolyze substrates different from nucleotides triphosphate, such as glucose-1-phosphate or alpha-glycero-phosphate. The enzyme is probably related to a mechanism of calcium transport."}
{"id": "PMID:210776", "title": "[Effect of cardiocrome on EEG arousal response (author's transl)].", "content": "The experiment was made on effect of Cardiocrome (containing Cytochrome c, Co-Carboxylase and Flavin mononucleotide), Cytochrome c and Cytidine diphosphate (CDP) choline on the EEG arousal response induced by electrical stimulation of mesencephalic reticular formation in 68 unanesthetized immobilized cats. The arousal response was accelerated by intravenous injection of Cardiocrome, Cytochrome c and CDP-choline. The accelerating effect of Cardiocrome was more prominet than that of Cytochrome c. In conclusion, it can be drawn that Cardiocrome has an arousal effect on consciousness.", "contents": "[Effect of cardiocrome on EEG arousal response (author's transl)]. The experiment was made on effect of Cardiocrome (containing Cytochrome c, Co-Carboxylase and Flavin mononucleotide), Cytochrome c and Cytidine diphosphate (CDP) choline on the EEG arousal response induced by electrical stimulation of mesencephalic reticular formation in 68 unanesthetized immobilized cats. The arousal response was accelerated by intravenous injection of Cardiocrome, Cytochrome c and CDP-choline. The accelerating effect of Cardiocrome was more prominet than that of Cytochrome c. In conclusion, it can be drawn that Cardiocrome has an arousal effect on consciousness."}
{"id": "PMID:210778", "title": "Ascorbic acid and dehydroascorbic acid in HeLa cells: their effect on the collagen-peptidase activity of glucose-deficient cultures.", "content": "HeLa cells in culture do not accumulate ascorbic acid unless ascorbic acid or dehydroascorbic acid is available in the medium. Collagen peptidase corresponding to the activity found in the invasive zone of tumours, and acid phosphatase, in HeLa cells cultured under normal conditions, are unaffected by ascorbic acid, but are reduced in cells deprived of carbohydrate. These reduced collagen-peptidase levels, but not acid phosphatase, are restored to the values of normal HeLa cells by ascorbic acid. The relevance of these findings is considered in the context of tumour growth and spread.", "contents": "Ascorbic acid and dehydroascorbic acid in HeLa cells: their effect on the collagen-peptidase activity of glucose-deficient cultures. HeLa cells in culture do not accumulate ascorbic acid unless ascorbic acid or dehydroascorbic acid is available in the medium. Collagen peptidase corresponding to the activity found in the invasive zone of tumours, and acid phosphatase, in HeLa cells cultured under normal conditions, are unaffected by ascorbic acid, but are reduced in cells deprived of carbohydrate. These reduced collagen-peptidase levels, but not acid phosphatase, are restored to the values of normal HeLa cells by ascorbic acid. The relevance of these findings is considered in the context of tumour growth and spread."}
{"id": "PMID:210780", "title": "Location and interactions of phospholipid and cholesterol in human low density lipoprotein from 31P nuclear magnetic resonance.", "content": "The major phospholipids, phosphatidylcholine and spingomyelin, of low density lipoprotein (LDL) are accessible to small amounts of Pr3+, suggesting that the head groups of all mobile phospholipids are on the surface of the particle in contact with the aqueous medium. The major source of the nuclear Overhauser effect enhancement of 31P resonances is the N-methyl proton of the choline moiety, indicating close N-methyl phosphate group interactions, probably similar to those found previously in phospholipid vesicles. This behavior of the phospholipid head groups in LDL is similar to that in small vesicles without cholesterol, suggesting that in LDL most of the cholesterol is not associated with mobile, surface phospholipids. In contrast to LDL, where the presence of a large protein immobilizes some phospholipid head groups, immobilization does not occur in high density lipoprotein, consistent with occurrence of smaller peptides in the latter.", "contents": "Location and interactions of phospholipid and cholesterol in human low density lipoprotein from 31P nuclear magnetic resonance. The major phospholipids, phosphatidylcholine and spingomyelin, of low density lipoprotein (LDL) are accessible to small amounts of Pr3+, suggesting that the head groups of all mobile phospholipids are on the surface of the particle in contact with the aqueous medium. The major source of the nuclear Overhauser effect enhancement of 31P resonances is the N-methyl proton of the choline moiety, indicating close N-methyl phosphate group interactions, probably similar to those found previously in phospholipid vesicles. This behavior of the phospholipid head groups in LDL is similar to that in small vesicles without cholesterol, suggesting that in LDL most of the cholesterol is not associated with mobile, surface phospholipids. In contrast to LDL, where the presence of a large protein immobilizes some phospholipid head groups, immobilization does not occur in high density lipoprotein, consistent with occurrence of smaller peptides in the latter."}
{"id": "PMID:210781", "title": "Cholesterol distribution and movement in the Mycoplasma gallisepticum cell membrane.", "content": "The time course and extent of transfer of [14C]-cholesterol from resting Mycoplasma gallisepticum cells or membrane preparations to high-density lipoproteins were studied. More than 90% of the total cholesterol in isolated, unsealed membrane preparations was exchanged in a single kinetic process. In intact cells, however, cholesterol exists in two different environments. Cholesterol in one environment, representing approximately 50% of the total unesterified cholesterol, is readily exchanged with the cholesterol of high-density lipoproteins, with a half-time of about 4 h at 37 degrees C. The rate of exchange of [14C]cholesterol from the other environment was exceedingly slow, with a half-time of about 18 days. The fraction of the total cholesterol in the readily exchangeable cholesterol pool in intact cells increased somewhat upon aging of the culture. Electron spin resonance spectra of nitroxide-labeled stearic acids incorporated into membranes of M. gallisepticum cells indicated increased rigidity at the late exponential phase of growth. These results suggest that cholesterol is present in approximately equal concentrations on both surfaces of the M. gallisepticum membrane and that in resting cells the rate of movement of cholesterol molecules from the inner to outer halves of the lipid bilayer is exceedingly slow or nonexistent.", "contents": "Cholesterol distribution and movement in the Mycoplasma gallisepticum cell membrane. The time course and extent of transfer of [14C]-cholesterol from resting Mycoplasma gallisepticum cells or membrane preparations to high-density lipoproteins were studied. More than 90% of the total cholesterol in isolated, unsealed membrane preparations was exchanged in a single kinetic process. In intact cells, however, cholesterol exists in two different environments. Cholesterol in one environment, representing approximately 50% of the total unesterified cholesterol, is readily exchanged with the cholesterol of high-density lipoproteins, with a half-time of about 4 h at 37 degrees C. The rate of exchange of [14C]cholesterol from the other environment was exceedingly slow, with a half-time of about 18 days. The fraction of the total cholesterol in the readily exchangeable cholesterol pool in intact cells increased somewhat upon aging of the culture. Electron spin resonance spectra of nitroxide-labeled stearic acids incorporated into membranes of M. gallisepticum cells indicated increased rigidity at the late exponential phase of growth. These results suggest that cholesterol is present in approximately equal concentrations on both surfaces of the M. gallisepticum membrane and that in resting cells the rate of movement of cholesterol molecules from the inner to outer halves of the lipid bilayer is exceedingly slow or nonexistent."}
{"id": "PMID:210782", "title": "Reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase: location of the hydrophobic, membrane-binding region at the carboxyl-terminal end and the masked amino terminus.", "content": "Microsomal NADH-cytochrome b5 reductase is an amphiphilic protein consisting of a hydrophilic (catalytic) region and a hydrophobic (membrane-binding) segment. Digestion of the reductase purified from rabbit liver microsomes with carboxypeptidase Y (CPY), but not with aminopeptidases, resulted in the abolishment of the capacities of the reductase to bind to phosphatidylcholine liposomes and to reconstitute an active NADH-cytochrome c reductase system upon mixing with cytochrome b5. The NADH-ferricyanide reductase activity of the flavoprotein was, however, inactivated only slightly by the CPY digestion. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino acid analyses indicated that the CPY treatment removed about 30 amino acid residues from the tcooh terminus of the reductase and that about 70% of the amino acids released were hydrophobic. It is concluded that the hydrophobic region of the reductase, responsible for both membrane binding and effective reconstitution of NADH-cytochrome c reductase activity, is located at the COOH-terminal portion of the molecule. No NH2-terminal residue could be detected in the intact and CPY-modified reductase preparations. The location of the hydrophobic, membrane-binding segment at the COOH-terminal end and the masked NH2 terminus have also been reported for cytochrome b5, another microsomal membrane protein.", "contents": "Reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase: location of the hydrophobic, membrane-binding region at the carboxyl-terminal end and the masked amino terminus. Microsomal NADH-cytochrome b5 reductase is an amphiphilic protein consisting of a hydrophilic (catalytic) region and a hydrophobic (membrane-binding) segment. Digestion of the reductase purified from rabbit liver microsomes with carboxypeptidase Y (CPY), but not with aminopeptidases, resulted in the abolishment of the capacities of the reductase to bind to phosphatidylcholine liposomes and to reconstitute an active NADH-cytochrome c reductase system upon mixing with cytochrome b5. The NADH-ferricyanide reductase activity of the flavoprotein was, however, inactivated only slightly by the CPY digestion. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino acid analyses indicated that the CPY treatment removed about 30 amino acid residues from the tcooh terminus of the reductase and that about 70% of the amino acids released were hydrophobic. It is concluded that the hydrophobic region of the reductase, responsible for both membrane binding and effective reconstitution of NADH-cytochrome c reductase activity, is located at the COOH-terminal portion of the molecule. No NH2-terminal residue could be detected in the intact and CPY-modified reductase preparations. The location of the hydrophobic, membrane-binding segment at the COOH-terminal end and the masked NH2 terminus have also been reported for cytochrome b5, another microsomal membrane protein."}
{"id": "PMID:210783", "title": "Sulfhydryl group reactivity of adenosine 3',5'-monophosphate dependent protein kinase from bovine heart: a probe of holoenzyme structure.", "content": "The spectrophotometric titration of SH groups in adenosine 3',5'-monophosphate (cAMP) dependent protein kinase from bovine heart muscle with 5,5'-dithiobis(2-nitrobenzoic acid)(DTNB) is described. The holoenzyme (R2C2) contains 16 SH groups, 12 of which react with DTNB in the native enzyme. The SH groups are distributed 2 per catalytic (C) and 4 per regulatory (R) subunit. The binding of cAMP to the holoenzyme or isolated R subunit prevents the reaction of one SH group per R subunit. Modification of SH groups, however, has only a small effect on cAMP binding to R. Reaction of the C subunit with DTNB results in less than 95% loss of catalytic activity. The kinetics of the DTNB reaction and the reversal of the inactivation process by treatment with dithiothreitol suggest that the inactivation is associated with SH group modification. Inactivation studies with the holoenzyme show that: (1) the R subunit inhibits DTNG inactivation of the C subunit in the absence of cAMP; (2) the rate of inactivation of the dephosphoholoenzyme in the presence of cAMP is considerably faster than that of the free catalytic subunit; and (3) the rate of inactivation of the phosphoholoenzyme in the presence of cAMP is faster than that of the C subunit but slower than the dephosphoholoenzyme. The results are interpreted as evidence for a significant interaction of the R and C subunits in the presence of saturating concentrations of cAMP. This interaction is modulated by the state of phosphorylation of R. To account for the inactivation data, a short-lived ternary complex containing R, C, and cAMP is postulated to be in rapid equilibrium with the subunits.", "contents": "Sulfhydryl group reactivity of adenosine 3',5'-monophosphate dependent protein kinase from bovine heart: a probe of holoenzyme structure. The spectrophotometric titration of SH groups in adenosine 3',5'-monophosphate (cAMP) dependent protein kinase from bovine heart muscle with 5,5'-dithiobis(2-nitrobenzoic acid)(DTNB) is described. The holoenzyme (R2C2) contains 16 SH groups, 12 of which react with DTNB in the native enzyme. The SH groups are distributed 2 per catalytic (C) and 4 per regulatory (R) subunit. The binding of cAMP to the holoenzyme or isolated R subunit prevents the reaction of one SH group per R subunit. Modification of SH groups, however, has only a small effect on cAMP binding to R. Reaction of the C subunit with DTNB results in less than 95% loss of catalytic activity. The kinetics of the DTNB reaction and the reversal of the inactivation process by treatment with dithiothreitol suggest that the inactivation is associated with SH group modification. Inactivation studies with the holoenzyme show that: (1) the R subunit inhibits DTNG inactivation of the C subunit in the absence of cAMP; (2) the rate of inactivation of the dephosphoholoenzyme in the presence of cAMP is considerably faster than that of the free catalytic subunit; and (3) the rate of inactivation of the phosphoholoenzyme in the presence of cAMP is faster than that of the C subunit but slower than the dephosphoholoenzyme. The results are interpreted as evidence for a significant interaction of the R and C subunits in the presence of saturating concentrations of cAMP. This interaction is modulated by the state of phosphorylation of R. To account for the inactivation data, a short-lived ternary complex containing R, C, and cAMP is postulated to be in rapid equilibrium with the subunits."}
{"id": "PMID:210784", "title": "Cobalt exchange in horse liver alcohol dehydrogenase.", "content": "The preparation of metal hybrid species of horse liver alcohol dehydrogenase is made possible by the development of carefully delineated systems of metal in equilibrium metal exchange employing equilibrium dialysis. The conditions which are optimal for the site-specific replacement of the catalytic and/or noncatalytic zinc atoms of the native enzyme by cobalt are not identical with those which are utilized for substitution with 65Zn. Thus, while certain 65Zn hybrids can be prepared by exploiting the differential effects of buffer anions, the cobalt hybrids are generated by critical adjustments in the pH of the dialysate. Factors which may determine the mechanism of metal replacement reactions include acid-assisted, ligand-assisted, and metal-assisted dechelation, steric restriction, and ligand denticity as well as physicochemical properties of the enzyme itself. The spectral characteristics of the catalytic and noncatalytic cobalt atoms reflect both the geometry of the coordination complexes and the nature of the ligands and serve as sensitive probes of these loci in the enzyme.", "contents": "Cobalt exchange in horse liver alcohol dehydrogenase. The preparation of metal hybrid species of horse liver alcohol dehydrogenase is made possible by the development of carefully delineated systems of metal in equilibrium metal exchange employing equilibrium dialysis. The conditions which are optimal for the site-specific replacement of the catalytic and/or noncatalytic zinc atoms of the native enzyme by cobalt are not identical with those which are utilized for substitution with 65Zn. Thus, while certain 65Zn hybrids can be prepared by exploiting the differential effects of buffer anions, the cobalt hybrids are generated by critical adjustments in the pH of the dialysate. Factors which may determine the mechanism of metal replacement reactions include acid-assisted, ligand-assisted, and metal-assisted dechelation, steric restriction, and ligand denticity as well as physicochemical properties of the enzyme itself. The spectral characteristics of the catalytic and noncatalytic cobalt atoms reflect both the geometry of the coordination complexes and the nature of the ligands and serve as sensitive probes of these loci in the enzyme."}
{"id": "PMID:210785", "title": "Purification and characterization of a marine bacterial collagenase.", "content": "A true collagenase was isolated from the culture fluid of a marine bacterium which has been designated Vibrio B-30 (ATCC 21250). Collagenase production was obtained only in media containing collagen or certain degradation products of collagen. Partial purification on DEAE-cellulose and Sephadex G-200 columns produced active enzyme which was free of nonspecific proteases but which contained two collagenases. The two collagenases have the same apparent molecular size, and evidence is presented to support the theory that one collagenase is derived from the other. Vibrio B-30 collagenase appears to be a tetramer with a molecular weight of about 105 000 composed of two different subunits (mol wt 24 000 and 28 000). Some of the properties of the Vibrio collagenase are compared with those of Clostridium histolyticum collagenase. Molecular weights, subunit structures, specificity and mode of collagen hydrolysis, insensitivity to diisopropyl fluorophosphate and calf serum, and sensitivity to certain metal ion complexing agents and isopropyl alcohol are similar for the collagenases from both organisms. However, Vibrio B-30 collagenase and Clostridium collagenase differ immunologically and electrophoretically.", "contents": "Purification and characterization of a marine bacterial collagenase. A true collagenase was isolated from the culture fluid of a marine bacterium which has been designated Vibrio B-30 (ATCC 21250). Collagenase production was obtained only in media containing collagen or certain degradation products of collagen. Partial purification on DEAE-cellulose and Sephadex G-200 columns produced active enzyme which was free of nonspecific proteases but which contained two collagenases. The two collagenases have the same apparent molecular size, and evidence is presented to support the theory that one collagenase is derived from the other. Vibrio B-30 collagenase appears to be a tetramer with a molecular weight of about 105 000 composed of two different subunits (mol wt 24 000 and 28 000). Some of the properties of the Vibrio collagenase are compared with those of Clostridium histolyticum collagenase. Molecular weights, subunit structures, specificity and mode of collagen hydrolysis, insensitivity to diisopropyl fluorophosphate and calf serum, and sensitivity to certain metal ion complexing agents and isopropyl alcohol are similar for the collagenases from both organisms. However, Vibrio B-30 collagenase and Clostridium collagenase differ immunologically and electrophoretically."}
{"id": "PMID:210787", "title": "In vitro and in vivo age-related modification of human erythrocyte phosphoribosyl pyrophosphate synthetase.", "content": "Upon storage, human erythrocyte phosphoribosyl pyrophosphate synthetase (PRibPP synthetase, EC 2.7.6.1) from normal individuals was found to undergo a spontaneous dissociation into active enzyme components of much smaller molecular mass (60 000--90 000). These modified forms of enzyme exhibit kinetic properties different from the original large molecular weight enzyme (over 200 000). The small active components can be reversibly associated to form larger molecules in the presence of purine ribonucleotides as well as phosphoribosyl pyrophosphate (PRibPP). ATP was found to be most effective in associating PRibPP synthetase, while guanylate nucleotides seem to have no effect. The large molecular weight components, once separated from the milieu, were not able to undergo further dissociation. Fresh or stored human white cell tissue homogenates were found to lack the low-molecular-weight enzyme under all our experimental conditions. A characteristic enzyme modification similar to that observed in stored erythrocyte was also noted in erythrocytes of increasing ages. The physiological significance of these findings to the regulatory function of PRibPP synthetase in purine metabolism in vivo is discussed.", "contents": "In vitro and in vivo age-related modification of human erythrocyte phosphoribosyl pyrophosphate synthetase. Upon storage, human erythrocyte phosphoribosyl pyrophosphate synthetase (PRibPP synthetase, EC 2.7.6.1) from normal individuals was found to undergo a spontaneous dissociation into active enzyme components of much smaller molecular mass (60 000--90 000). These modified forms of enzyme exhibit kinetic properties different from the original large molecular weight enzyme (over 200 000). The small active components can be reversibly associated to form larger molecules in the presence of purine ribonucleotides as well as phosphoribosyl pyrophosphate (PRibPP). ATP was found to be most effective in associating PRibPP synthetase, while guanylate nucleotides seem to have no effect. The large molecular weight components, once separated from the milieu, were not able to undergo further dissociation. Fresh or stored human white cell tissue homogenates were found to lack the low-molecular-weight enzyme under all our experimental conditions. A characteristic enzyme modification similar to that observed in stored erythrocyte was also noted in erythrocytes of increasing ages. The physiological significance of these findings to the regulatory function of PRibPP synthetase in purine metabolism in vivo is discussed."}
{"id": "PMID:210788", "title": "Kinetics of rac-1-oleyl-2-[4-(3-pyrenyl)butanoyl]glycerol transfer between high density lipoproteins.", "content": "The mechanism of transfer of diglyceride between high density lipoproteins (HDL) was investigated with a pyrene-containing analogue whose fluorescent properties depend on the microscopic concentration in the lipoprotein. Transfer rates were first order, rapid (3.5s-1), and invariant over a 100-fold range of HDL concentration and over a 10-fold range of rac-1-oleyl-2-[4-(3-pyrenyl)butanoyl]glycerol concentrations. Similar behavior of the probe was observed with HDL3, although the rate was 40% slower. These results support a mechanism in which rate-limiting dissociation of the diglyceride analogue from one HDL particle into the aqueous phase precedes rapid diffusion and subsequent uptake by another such particle.", "contents": "Kinetics of rac-1-oleyl-2-[4-(3-pyrenyl)butanoyl]glycerol transfer between high density lipoproteins. The mechanism of transfer of diglyceride between high density lipoproteins (HDL) was investigated with a pyrene-containing analogue whose fluorescent properties depend on the microscopic concentration in the lipoprotein. Transfer rates were first order, rapid (3.5s-1), and invariant over a 100-fold range of HDL concentration and over a 10-fold range of rac-1-oleyl-2-[4-(3-pyrenyl)butanoyl]glycerol concentrations. Similar behavior of the probe was observed with HDL3, although the rate was 40% slower. These results support a mechanism in which rate-limiting dissociation of the diglyceride analogue from one HDL particle into the aqueous phase precedes rapid diffusion and subsequent uptake by another such particle."}
{"id": "PMID:210789", "title": "Enzymatically inactive, exchange-inert Co(III)-carboxypeptidase A: role of inner sphere coordination in peptide and ester catalysis.", "content": "Catalytically inactive, exchange-inert Co(III)-carboxypeptidase A has been prepared by reaction of Co(II)-carboxypeptidase A with the active-site-directed oxidizing agent m-chloroperbenzoic acid. Co(III)-carboxypeptidase A, isolated by affinity gel filtration chromatography, has the same amino acid composition and molecular weight as the starting material and contains 0.95 g-atom/mol of cobalt and 0.01 g-atom/mol of zinc. Its electron paramagnetic resonance, circular dichroic, magnetic circular dichroic, and visible absorption spectra are consistent with those of octahedral Co(III) model complexes. Co(III)-caboxypeptidase A  is essentially devoid of catalytic activity toward both peptide and ester substrates of the native enzyme, and stopped-flow fluorescence studies with dansylated substrates show that it binds peptides, but not esters. Furthermore, the protein does not react with either type of substrate to yield a single turnover. The implications of these findings to the mechanism of action of carboxypeptidase A are discussed in the light of the \"metal-carbonyl\" and \"metal-hydroxide\" hypotheses. Since Co(III)-carboxypeptidase A does not bind esters, inner-sphere coordination to the metal appears to be necessary for ester binding. All attempts to prepare Co(III)-carboxypeptidase A by treatment of Co(II)-carboxypeptidase A with hydrogen peroxide according to previously published procedures (Kang, E.P., Storm, C.B., & Carson, F.W. (1975) J. Am. Chem. Soc. 97, 6723) have been unsuccessful, and the present results do not confirm earlier reports that Co(III)-carboxypeptidase A exhibits esterase activity or that its activity is dependent on the method of preparation of the precursor Co(II)-carboxypeptidase A (Jones, M.M., Hunt, J.B., Storm, C.B., Evans, P.S., Carson, F.W. & Pauli, W.J. (1977) Biochem. Biophys. Res. Commun. 75, 253). These findings call for a reexamination of mechanistic conclusions based on the assumption that Co(III)-carboxypeptidase A is an active esterase.", "contents": "Enzymatically inactive, exchange-inert Co(III)-carboxypeptidase A: role of inner sphere coordination in peptide and ester catalysis. Catalytically inactive, exchange-inert Co(III)-carboxypeptidase A has been prepared by reaction of Co(II)-carboxypeptidase A with the active-site-directed oxidizing agent m-chloroperbenzoic acid. Co(III)-carboxypeptidase A, isolated by affinity gel filtration chromatography, has the same amino acid composition and molecular weight as the starting material and contains 0.95 g-atom/mol of cobalt and 0.01 g-atom/mol of zinc. Its electron paramagnetic resonance, circular dichroic, magnetic circular dichroic, and visible absorption spectra are consistent with those of octahedral Co(III) model complexes. Co(III)-caboxypeptidase A  is essentially devoid of catalytic activity toward both peptide and ester substrates of the native enzyme, and stopped-flow fluorescence studies with dansylated substrates show that it binds peptides, but not esters. Furthermore, the protein does not react with either type of substrate to yield a single turnover. The implications of these findings to the mechanism of action of carboxypeptidase A are discussed in the light of the \"metal-carbonyl\" and \"metal-hydroxide\" hypotheses. Since Co(III)-carboxypeptidase A does not bind esters, inner-sphere coordination to the metal appears to be necessary for ester binding. All attempts to prepare Co(III)-carboxypeptidase A by treatment of Co(II)-carboxypeptidase A with hydrogen peroxide according to previously published procedures (Kang, E.P., Storm, C.B., & Carson, F.W. (1975) J. Am. Chem. Soc. 97, 6723) have been unsuccessful, and the present results do not confirm earlier reports that Co(III)-carboxypeptidase A exhibits esterase activity or that its activity is dependent on the method of preparation of the precursor Co(II)-carboxypeptidase A (Jones, M.M., Hunt, J.B., Storm, C.B., Evans, P.S., Carson, F.W. & Pauli, W.J. (1977) Biochem. Biophys. Res. Commun. 75, 253). These findings call for a reexamination of mechanistic conclusions based on the assumption that Co(III)-carboxypeptidase A is an active esterase."}
{"id": "PMID:210790", "title": "Hemorrhagic toxins from Western diamondback rattlesnake (Crotalus atrox) venom: isolation and characterization of five toxins and the role of zinc in hemorrhagic toxin e.", "content": "Five previously unknown hemorrhagic proteins, designated hemorrhagic toxins a,b,c,d, and e, were isolated from the venom of the western diamondback rattlesnake (Crotalus atrox). Molecular weights of hemorrhagic toxins a-e were determined to be 68 000, 24 000, 24 000, 24 000, and 25 700, respectively, by sodium dodecyl sulfate-phosphate gel electrophoresis using various polyacrylamide gel concentrations. Amino acid composition showed a total of 636, 200, 213, 214, and 219 amino acids for hemorrhagic toxins a-e, respectively. All the hemorrhagic toxins were found to lose their hemorrhagic activities with the metal chelators ethylenediaminetetraacetic acid and 1, 10-phenanthroline. All the hemorrhagic toxins were found to contain approximately 1 mol of zinc/mol of toxin, and they were all demonstrated to be proteolytic when dimethylcasein and dimethylhemoglobin were used as substrates. When zinc was removed from hemorrhagic toxin e with 1,10-phenanthroline, both both the proteolytic and hemorrhagic activities were equally inhibited. When the apohemorrhagic toxin e thus produced was incubated with zinc, the hemorrhagic and proteolytic activities were regenerated to the same extent. CD, UV, and Raman spectroscopy were used to study the structure of native hemorrhagin toxin e  as well as the structural changes caused by zinc removal. From CD spectroscopy the native toxin was estimated to consist of 23% alpha helix, 6% beta structure, and 71% random-coil conformation. When over 90% of the zinc was removed, the alpha-helix content dropped from 23 to 7%.", "contents": "Hemorrhagic toxins from Western diamondback rattlesnake (Crotalus atrox) venom: isolation and characterization of five toxins and the role of zinc in hemorrhagic toxin e. Five previously unknown hemorrhagic proteins, designated hemorrhagic toxins a,b,c,d, and e, were isolated from the venom of the western diamondback rattlesnake (Crotalus atrox). Molecular weights of hemorrhagic toxins a-e were determined to be 68 000, 24 000, 24 000, 24 000, and 25 700, respectively, by sodium dodecyl sulfate-phosphate gel electrophoresis using various polyacrylamide gel concentrations. Amino acid composition showed a total of 636, 200, 213, 214, and 219 amino acids for hemorrhagic toxins a-e, respectively. All the hemorrhagic toxins were found to lose their hemorrhagic activities with the metal chelators ethylenediaminetetraacetic acid and 1, 10-phenanthroline. All the hemorrhagic toxins were found to contain approximately 1 mol of zinc/mol of toxin, and they were all demonstrated to be proteolytic when dimethylcasein and dimethylhemoglobin were used as substrates. When zinc was removed from hemorrhagic toxin e with 1,10-phenanthroline, both both the proteolytic and hemorrhagic activities were equally inhibited. When the apohemorrhagic toxin e thus produced was incubated with zinc, the hemorrhagic and proteolytic activities were regenerated to the same extent. CD, UV, and Raman spectroscopy were used to study the structure of native hemorrhagin toxin e  as well as the structural changes caused by zinc removal. From CD spectroscopy the native toxin was estimated to consist of 23% alpha helix, 6% beta structure, and 71% random-coil conformation. When over 90% of the zinc was removed, the alpha-helix content dropped from 23 to 7%."}
{"id": "PMID:210791", "title": "Isolation and characterization of polyadenylate-containing RNA from Bacillus brevis.", "content": "A substantial fraction (30--40%) of pulse-labeled RNA from exponentially growing cells of Bacillus brevis contains polyadenylate sequences, as measured by adsorption to oligo(dT)-cellulose. The weight-average length of poly(A) tracts obtained after digestion with pancreatic and T1 ribonucleases is 60 nucleotide residues. Susceptibility to degradation by snake venom phosphodiesterase after ribonuclease degradation indicates that the poly(A) sequences are located near the 3' ends of the RNA chains, but that in 40% of the material at least one internal pyrimidine nucleotide residue intervenes between the poly(A) tract and the 3'-hydroxyl terminus. These pyrimidine nucleotides consist of 65% cytidylate and 35% uridylate residues. In the remaining RNA chains, the poly(A) sequence is directly at the 3'-terminus, but the possibility cannot be excluded that a small fraction of this material may contain a 3'-hydroxyl terminal guanylate residue. The weight-average sedimentation coefficient of poly(A)-containing RNA is 12.5 S, corresponding to a polynucleotide chain length of 800--900 residues. This is in a size range expected for messenger RNA, a possibility which is also supported by the observation that pulse-labeled RNA has a considerably higher poly(A) content than long-term labeled RNA.", "contents": "Isolation and characterization of polyadenylate-containing RNA from Bacillus brevis. A substantial fraction (30--40%) of pulse-labeled RNA from exponentially growing cells of Bacillus brevis contains polyadenylate sequences, as measured by adsorption to oligo(dT)-cellulose. The weight-average length of poly(A) tracts obtained after digestion with pancreatic and T1 ribonucleases is 60 nucleotide residues. Susceptibility to degradation by snake venom phosphodiesterase after ribonuclease degradation indicates that the poly(A) sequences are located near the 3' ends of the RNA chains, but that in 40% of the material at least one internal pyrimidine nucleotide residue intervenes between the poly(A) tract and the 3'-hydroxyl terminus. These pyrimidine nucleotides consist of 65% cytidylate and 35% uridylate residues. In the remaining RNA chains, the poly(A) sequence is directly at the 3'-terminus, but the possibility cannot be excluded that a small fraction of this material may contain a 3'-hydroxyl terminal guanylate residue. The weight-average sedimentation coefficient of poly(A)-containing RNA is 12.5 S, corresponding to a polynucleotide chain length of 800--900 residues. This is in a size range expected for messenger RNA, a possibility which is also supported by the observation that pulse-labeled RNA has a considerably higher poly(A) content than long-term labeled RNA."}
{"id": "PMID:210792", "title": "Identification of the transcribing DNA strand for the deoxynucleotide kinase gene of bacteriophage T2.", "content": "A modified procedure was developed which allows RNA--DNA hybridization reactions to be performed without the loss in translational capacity of mRNA which accompanies hybridization at elevated temperatures or in the presence of the denaturing agent formamide. Separated l and r strands of bacteriophage T2 DNA were hybridized in the presence of 4 M sodium perchlorate at 37 degrees C with total RNA from infected cells. After passage of the hybridization mixture through a nitrocellulose column to remove single-strand DNA and DNA--RNA hybrids, the eluent was measured for its capacity to promote deoxynucleotide kinase (gene 1) synthesis in an in vitro protein-synthesizing system derived from uninfected Escherichia coli. With this procedure, which should be of general use for any message whose product can be measured either enzymatically, immunologically, or by location in an acrylamide gel, it was demonstrated that deoxynucleotide kinase mRNA is transcribed from the l strand of bacteriophage T2 DNA. By titrating with l strand DNA, the number of deoxynucleotide kinase transcripts present 9 min after T2 phage infection at 30 degrees C was estimated to be about 38 copies per cell.", "contents": "Identification of the transcribing DNA strand for the deoxynucleotide kinase gene of bacteriophage T2. A modified procedure was developed which allows RNA--DNA hybridization reactions to be performed without the loss in translational capacity of mRNA which accompanies hybridization at elevated temperatures or in the presence of the denaturing agent formamide. Separated l and r strands of bacteriophage T2 DNA were hybridized in the presence of 4 M sodium perchlorate at 37 degrees C with total RNA from infected cells. After passage of the hybridization mixture through a nitrocellulose column to remove single-strand DNA and DNA--RNA hybrids, the eluent was measured for its capacity to promote deoxynucleotide kinase (gene 1) synthesis in an in vitro protein-synthesizing system derived from uninfected Escherichia coli. With this procedure, which should be of general use for any message whose product can be measured either enzymatically, immunologically, or by location in an acrylamide gel, it was demonstrated that deoxynucleotide kinase mRNA is transcribed from the l strand of bacteriophage T2 DNA. By titrating with l strand DNA, the number of deoxynucleotide kinase transcripts present 9 min after T2 phage infection at 30 degrees C was estimated to be about 38 copies per cell."}
{"id": "PMID:210794", "title": "Nuclear protein modification and chromatin substructure. 2. Internucleosomal localization of poly(adenosine diphosphate-ribose) polymerase.", "content": "Definitive evidence for poly(ADP-Rib) polymerase activity is localized within internucleosomal \"linker\" regions of HeLa cell chromatin is presented. This evidence was based on the following criteria: the enzyme activity did not coincide with the position of core particles in a sucrose gradient but was displaced to that part of the gradient which is enriched in monomers with linker regions. This was not due to dimer contamination, since resedimentation did not affect the enzyme activity in relation to the monomer. A new method of assaying enzyme activity directly in polyacrylamide gels following the separation of monomers and dimers showed that only dimers and monomers with linker regions contained activity. When dimers were digested, the enzyme activity moved from the dimer to the monomer with linker.", "contents": "Nuclear protein modification and chromatin substructure. 2. Internucleosomal localization of poly(adenosine diphosphate-ribose) polymerase. Definitive evidence for poly(ADP-Rib) polymerase activity is localized within internucleosomal \"linker\" regions of HeLa cell chromatin is presented. This evidence was based on the following criteria: the enzyme activity did not coincide with the position of core particles in a sucrose gradient but was displaced to that part of the gradient which is enriched in monomers with linker regions. This was not due to dimer contamination, since resedimentation did not affect the enzyme activity in relation to the monomer. A new method of assaying enzyme activity directly in polyacrylamide gels following the separation of monomers and dimers showed that only dimers and monomers with linker regions contained activity. When dimers were digested, the enzyme activity moved from the dimer to the monomer with linker."}
{"id": "PMID:210796", "title": "Uridine diphosphate galactose 4-epimerase: nucleotide and 8-anilino-1-naphthalenesulfonate binding properties of the substrate binding site.", "content": "Escherichia coli UDP-galactose 4-epimerase in its native form (epimerase.NAD) binds 8-anilino-1-naphthalenesulfonate (ANS) at one tight binding site per dimer with a dissociation constant of 25.9 +/- 2.1 micrometer at pH 8.5 and 27 degrees C. This appears to be the substrate binding site, as indicated by the fact that ANS is a kinetically competitive reversible inhibitor with a Ki of 27.5 micrometer and by the fact that ANS competes with UMP for binding to the enzyme. Upon binding at this site the fluorescence quantum yield of ANS is enhanced 185-fold, and its emission spectrum is blue shifted from a lambdamax of 515 to 470.nm, which suggests that the binding site is shielded from water and probably hydrophobic. Competitive binding experiments with nucleosides and nucleotides indicate that nucleotide binding at this site involves coupled hydrophobic and electrostatic interactions. The reduced form of the enzyme (epimerase.NADH) has no detectable binding affinity for ANS. The marked difference in the affinities of the native and reduced enzymes for ANS is interpreted to be a manifestation of a conformational difference between these enzyme forms.", "contents": "Uridine diphosphate galactose 4-epimerase: nucleotide and 8-anilino-1-naphthalenesulfonate binding properties of the substrate binding site. Escherichia coli UDP-galactose 4-epimerase in its native form (epimerase.NAD) binds 8-anilino-1-naphthalenesulfonate (ANS) at one tight binding site per dimer with a dissociation constant of 25.9 +/- 2.1 micrometer at pH 8.5 and 27 degrees C. This appears to be the substrate binding site, as indicated by the fact that ANS is a kinetically competitive reversible inhibitor with a Ki of 27.5 micrometer and by the fact that ANS competes with UMP for binding to the enzyme. Upon binding at this site the fluorescence quantum yield of ANS is enhanced 185-fold, and its emission spectrum is blue shifted from a lambdamax of 515 to 470.nm, which suggests that the binding site is shielded from water and probably hydrophobic. Competitive binding experiments with nucleosides and nucleotides indicate that nucleotide binding at this site involves coupled hydrophobic and electrostatic interactions. The reduced form of the enzyme (epimerase.NADH) has no detectable binding affinity for ANS. The marked difference in the affinities of the native and reduced enzymes for ANS is interpreted to be a manifestation of a conformational difference between these enzyme forms."}
{"id": "PMID:210797", "title": "Structure of a major glycophosphoceramide from tobacco leaves, PSL-I: 2-deoxy-2-acetamido-D-glucopyranosyl(alpha1 leads to 4)-D-glucuronopyranosyl(alpha1 leads to 2)myoinositol-1-O-phosphoceramide.", "content": "The chemical structure of a major glycophosphoceramide from tobacco leaves, called PSL-I [K. Kaul and R. L. Lester (1975), Plant Physiol. 55, 120], has now been characterized as 2-deoxy-2-acetamido-D-glucopyranosyl(alpha1 leads to 4)D-glucuronopyranosyl(alpha1 leads to 2)myoinositol-1-O-phosphoceramide. Sites of glycoside linkage were determined by (1) methylation analysis on a trisaccharide isolated by degradation of carboxyl-reduced PSL-I and (2) periodate oxidation experiments on PSL-I. The resulting products were identified with gas chromatography/mass spectrometry. Anomeric configurations were determined by resistance of the sugars in the peracetylated trisaccharide to chromium trioxide treatment.", "contents": "Structure of a major glycophosphoceramide from tobacco leaves, PSL-I: 2-deoxy-2-acetamido-D-glucopyranosyl(alpha1 leads to 4)-D-glucuronopyranosyl(alpha1 leads to 2)myoinositol-1-O-phosphoceramide. The chemical structure of a major glycophosphoceramide from tobacco leaves, called PSL-I [K. Kaul and R. L. Lester (1975), Plant Physiol. 55, 120], has now been characterized as 2-deoxy-2-acetamido-D-glucopyranosyl(alpha1 leads to 4)D-glucuronopyranosyl(alpha1 leads to 2)myoinositol-1-O-phosphoceramide. Sites of glycoside linkage were determined by (1) methylation analysis on a trisaccharide isolated by degradation of carboxyl-reduced PSL-I and (2) periodate oxidation experiments on PSL-I. The resulting products were identified with gas chromatography/mass spectrometry. Anomeric configurations were determined by resistance of the sugars in the peracetylated trisaccharide to chromium trioxide treatment."}
{"id": "PMID:210798", "title": "Steps involved in the processing of common precursor forms of adrenocorticotropin and endorphin in cultures of mouse pituitary cells.", "content": "The initial steps in the processing of the common precursor to adrenocorticotropin (ACTH) and endorphin in mouse pituitary tumor 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 (29K ACTH-endorphin), 32 000 (32K ACTH-endorphin) and 34 000 (34K ACTH-endorphin). These forms have a 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 the tryptic peptide containing the alpha(22--39) sequence of ACTH. Similar heterogeneity in carbohydrate has been observed in some of the smaller molecular weight forms of ACTH which are resolved by NaDodSO4 gel electrophoresis. Pulse chase and continuous labeling studies using radioactive amino acids and sugars suggest that the 29K ACTH-endorphin is converted to 32K and 34K ACTH-endorphin by the addition of carbohydrate. The glycopeptide and pulse chase studies suggest that 29K ACTH-endorphin is at a branch point in the processing pathways. It can either be converted to 4.5K ACTH by proteolytic processing or to 32K ACTH-endorphin by the further addition of carbohydrate. The 32K ACTH-endorphin can then be converted to 13K ACTH, the glycosylated form of 4.5K ACTH (Eipper, B.A., & Mains,, R.E. (1977) J.Biol. Chem.252, 882), by proteolytic processing. A comparison of the distribution of the different molecular weight forms of ACTH and endorphin in mouse pituitary extracts and in the mouse pituitary tumor cells reveals that the pituitary contains all of the forms of ACTH and endorphin seen in the tumor cells, including the three forms of the ACTH-endorphin precursor. However, the molecular weight distribution of the forms in the anterior lobe is very different from that in the intermediate lobe of mouse pituitary.", "contents": "Steps involved in the processing of common precursor forms of adrenocorticotropin and endorphin in cultures of mouse pituitary cells. The initial steps in the processing of the common precursor to adrenocorticotropin (ACTH) and endorphin in mouse pituitary tumor 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 (29K ACTH-endorphin), 32 000 (32K ACTH-endorphin) and 34 000 (34K ACTH-endorphin). These forms have a 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 the tryptic peptide containing the alpha(22--39) sequence of ACTH. Similar heterogeneity in carbohydrate has been observed in some of the smaller molecular weight forms of ACTH which are resolved by NaDodSO4 gel electrophoresis. Pulse chase and continuous labeling studies using radioactive amino acids and sugars suggest that the 29K ACTH-endorphin is converted to 32K and 34K ACTH-endorphin by the addition of carbohydrate. The glycopeptide and pulse chase studies suggest that 29K ACTH-endorphin is at a branch point in the processing pathways. It can either be converted to 4.5K ACTH by proteolytic processing or to 32K ACTH-endorphin by the further addition of carbohydrate. The 32K ACTH-endorphin can then be converted to 13K ACTH, the glycosylated form of 4.5K ACTH (Eipper, B.A., & Mains,, R.E. (1977) J.Biol. Chem.252, 882), by proteolytic processing. A comparison of the distribution of the different molecular weight forms of ACTH and endorphin in mouse pituitary extracts and in the mouse pituitary tumor cells reveals that the pituitary contains all of the forms of ACTH and endorphin seen in the tumor cells, including the three forms of the ACTH-endorphin precursor. However, the molecular weight distribution of the forms in the anterior lobe is very different from that in the intermediate lobe of mouse pituitary."}
{"id": "PMID:210799", "title": "Cycloleucine blocks 5'-terminal and internal methylations of avian sarcoma virus genome RNA.", "content": "Cycloleucine, a competitive inhibitor of ATP:  L-methionine S-adenosyltransferase in vitro, has been used to reduce intracellular concentrations of S-adenosylmethionine and by this means to inhibit virion RNA methylation in chicken embryo cells that are infected with B77 avian sarcoma virus. Under conditions of cycloleucine treatment, where virus production as measured by incorporation of radioactive precursors or by number of infectious particles is not significantly affected, the internal m6A methylations of the avian sarcoma virus genome RNA are inhibited greater than 90%. The predominant 5'-terminal structure in viral RNA produced by treated cells in m7G(5')pppG (cap zero) rather than m7G-(5')pppGm (cap 1). It appears from these results that internal m6A and penultimate ribose methylations are not required for avian sarcoma RNA synthesis and function. Furthermore, these methylations are apparently not required for transport of genome RNA to virus assembly sites. The insensitivity of the 5'-terminal m7G methylation to inhibition by cycloleucine suggests that the affinity of S-adenosylmethionine for 7-methylguanosine methyltransferase is significantly greater than for the 2'-0-methyltransferases or the N6-methyltransferases.", "contents": "Cycloleucine blocks 5'-terminal and internal methylations of avian sarcoma virus genome RNA. Cycloleucine, a competitive inhibitor of ATP:  L-methionine S-adenosyltransferase in vitro, has been used to reduce intracellular concentrations of S-adenosylmethionine and by this means to inhibit virion RNA methylation in chicken embryo cells that are infected with B77 avian sarcoma virus. Under conditions of cycloleucine treatment, where virus production as measured by incorporation of radioactive precursors or by number of infectious particles is not significantly affected, the internal m6A methylations of the avian sarcoma virus genome RNA are inhibited greater than 90%. The predominant 5'-terminal structure in viral RNA produced by treated cells in m7G(5')pppG (cap zero) rather than m7G-(5')pppGm (cap 1). It appears from these results that internal m6A and penultimate ribose methylations are not required for avian sarcoma RNA synthesis and function. Furthermore, these methylations are apparently not required for transport of genome RNA to virus assembly sites. The insensitivity of the 5'-terminal m7G methylation to inhibition by cycloleucine suggests that the affinity of S-adenosylmethionine for 7-methylguanosine methyltransferase is significantly greater than for the 2'-0-methyltransferases or the N6-methyltransferases."}
{"id": "PMID:210801", "title": "Influence of quaternary structure of the globin on thermal spin equilibria in different methemoglobin derivatives.", "content": "We have measured the paramagnetic susceptibilities of sperm whale azide metmyoglobin and of carp azide, thiocyanate, and nitrite methemoglobin in the quaternary oxy (R) and deoxy (T) structures between about 300 and 90 K, using a new sensitive superconducting magnetometer. We have also measured the pressure dependence of the high- and low-spin optical absorption bands of azide metmyoglobin and of carp azide methemoglobin in the R and T structures between 1 and 2000-4000 atmospheres. At low temperatures all the derivatives show normal Curie behavior, but above 200-250 K this is reversed, so that a thermal spin equilibrium is set up and the paramagnetic susceptibilities rise steeply with rising temperature. At all temperatures the effective magnetic moments in the T structure are higher than in the R structure. The magnetic data for azide methemoglobin have been subjected to detailed analysis. Below 250 K the magnetic moment in the R structure is 1.98 microB, characteristic of pure low spin, but that in the T structure is 2.80 microB, suggestive of a random mixture of high- and low-spin centers which have become frozen in by the immobility of the surrounding protein. Comparison of the thermal spin equilibria above 250 K shows that in the T structure the equilibrium is biased toward higher spin by the equivalent of about 1 kcal/mol relative to the R structure. Hydrostatic pressure reduces the optical density of the high-spin band at 630 nm and increases that of the low-spin bands at 541 and 573 nm. We have calibrated the optical density of the band at 630 nm against the measured paramagnetic susceptibilities of sperm whale azide metmyoglobin and carp azide methemoglobin in the R and T structures and have used this calibration to determine the dependence of the spin equilibria on hydrostatic pressure; this has allowed us to calculate the volume contraction associated with the transition from the fully high to the fully low-spin state. This amounts to -6.7 and -13.3 mL/mol heme for carp azide methemoglobins in the R and T structures, respectively, and to -12.5 mL/mol heme for azide metmyoglobin. These volume contractions are larger than those of about -4 mL/mol Fe found in synthetic iron chelates. Apparently stereochemical changes of the globin surrounding the heme also contribute to the volume changes; these must be larger in the T than in the R structure. The significance of these observations for the mechanism of heme-heme interaction is discussed.", "contents": "Influence of quaternary structure of the globin on thermal spin equilibria in different methemoglobin derivatives. We have measured the paramagnetic susceptibilities of sperm whale azide metmyoglobin and of carp azide, thiocyanate, and nitrite methemoglobin in the quaternary oxy (R) and deoxy (T) structures between about 300 and 90 K, using a new sensitive superconducting magnetometer. We have also measured the pressure dependence of the high- and low-spin optical absorption bands of azide metmyoglobin and of carp azide methemoglobin in the R and T structures between 1 and 2000-4000 atmospheres. At low temperatures all the derivatives show normal Curie behavior, but above 200-250 K this is reversed, so that a thermal spin equilibrium is set up and the paramagnetic susceptibilities rise steeply with rising temperature. At all temperatures the effective magnetic moments in the T structure are higher than in the R structure. The magnetic data for azide methemoglobin have been subjected to detailed analysis. Below 250 K the magnetic moment in the R structure is 1.98 microB, characteristic of pure low spin, but that in the T structure is 2.80 microB, suggestive of a random mixture of high- and low-spin centers which have become frozen in by the immobility of the surrounding protein. Comparison of the thermal spin equilibria above 250 K shows that in the T structure the equilibrium is biased toward higher spin by the equivalent of about 1 kcal/mol relative to the R structure. Hydrostatic pressure reduces the optical density of the high-spin band at 630 nm and increases that of the low-spin bands at 541 and 573 nm. We have calibrated the optical density of the band at 630 nm against the measured paramagnetic susceptibilities of sperm whale azide metmyoglobin and carp azide methemoglobin in the R and T structures and have used this calibration to determine the dependence of the spin equilibria on hydrostatic pressure; this has allowed us to calculate the volume contraction associated with the transition from the fully high to the fully low-spin state. This amounts to -6.7 and -13.3 mL/mol heme for carp azide methemoglobins in the R and T structures, respectively, and to -12.5 mL/mol heme for azide metmyoglobin. These volume contractions are larger than those of about -4 mL/mol Fe found in synthetic iron chelates. Apparently stereochemical changes of the globin surrounding the heme also contribute to the volume changes; these must be larger in the T than in the R structure. The significance of these observations for the mechanism of heme-heme interaction is discussed."}
{"id": "PMID:210802", "title": "Characterization of a new photoaffinity derivative of ouabain: labeling of the large polypeptide and of a proteolipid component of the Na, K-ATPase.", "content": "We have synthesized 2-nitro-5-azidobenzoyl (NAB) derivatives of ouabain as photoaffinity labels of the cardiac glyocoside binding site of Na, K-ATPase. [3HzNAB-ouabain was found to bind to the same number of sites on Na, K-ATPase (purified from pig kidney outer medulla) as ouabain (1.9 nmol/mg), with approximately the same affinity (Kk(ouabain)/Kd(NAB-ouabain) congruent to 1.6), and ouabain was fully competitive uith NAB-ouabain at these sites. NAB-ouabain binding and inhibition were reversible in the dark, but on exposure to ultraviolet light (310-370 nm) 30-40% of the binding and ihibition became irreversible; this binding was shown to be covalent by stability to trichloroacetic acid, organic solvents, and heat denaturation. Covalent labeling was prevented by photolysis of NAB-ouabain prior to the experiment, or by prior incubation of the enzyme with ouabain. On sodium dodecyl suffate-polyacrylamide gels of labeled Na,K-ATPase, about half of the covalently bound [3H]NAB-ouabain migrated with the large polypeptide (molecular weight congruent to 95 000), and half migrated with a small polypeptide (molecular weight congruent to 12 000); noncovalently bound NAB-ouabain (60-70% of total label) ran with the tracking dye. A similar labeling pattern was obtained utilizing NaI microsomes prepared from pig kidney outer medulla. The small polypeptide was characterized as an acidic proteolipid by extractability into acid chloroform/methanol; labeling of this component by NAB-ouabain is the first demonstration that it is directly associated with the Na,K-ATPase. The results of our characterization of NAB-ouabain show that it has the required specificity, covalency, and efficiency of labeling for application in structural studies of Na,K-ATPase subunit interactions.", "contents": "Characterization of a new photoaffinity derivative of ouabain: labeling of the large polypeptide and of a proteolipid component of the Na, K-ATPase. We have synthesized 2-nitro-5-azidobenzoyl (NAB) derivatives of ouabain as photoaffinity labels of the cardiac glyocoside binding site of Na, K-ATPase. [3HzNAB-ouabain was found to bind to the same number of sites on Na, K-ATPase (purified from pig kidney outer medulla) as ouabain (1.9 nmol/mg), with approximately the same affinity (Kk(ouabain)/Kd(NAB-ouabain) congruent to 1.6), and ouabain was fully competitive uith NAB-ouabain at these sites. NAB-ouabain binding and inhibition were reversible in the dark, but on exposure to ultraviolet light (310-370 nm) 30-40% of the binding and ihibition became irreversible; this binding was shown to be covalent by stability to trichloroacetic acid, organic solvents, and heat denaturation. Covalent labeling was prevented by photolysis of NAB-ouabain prior to the experiment, or by prior incubation of the enzyme with ouabain. On sodium dodecyl suffate-polyacrylamide gels of labeled Na,K-ATPase, about half of the covalently bound [3H]NAB-ouabain migrated with the large polypeptide (molecular weight congruent to 95 000), and half migrated with a small polypeptide (molecular weight congruent to 12 000); noncovalently bound NAB-ouabain (60-70% of total label) ran with the tracking dye. A similar labeling pattern was obtained utilizing NaI microsomes prepared from pig kidney outer medulla. The small polypeptide was characterized as an acidic proteolipid by extractability into acid chloroform/methanol; labeling of this component by NAB-ouabain is the first demonstration that it is directly associated with the Na,K-ATPase. The results of our characterization of NAB-ouabain show that it has the required specificity, covalency, and efficiency of labeling for application in structural studies of Na,K-ATPase subunit interactions."}
{"id": "PMID:210803", "title": "The role of the membrane-bound iron-sulphur centres A and B in the photosystem I reaction centre of spinach chloroplasts.", "content": "Photosystem I particles prepared from spinach chloroplast using Triton X-100 were frozen in the dark with the bound iron-sulphur Centre A reduced. Illumination at cryogenic temperatures of such samples demonstrated the photoreduction of the second bound iron-sulphur Centre B. Due to electron spin-electron spin interaction between these two bound iron-sulphur centres, it was not possible to quantify amounts of Centre B relative to the other components of the Photosystem I reaction centre by simulating the line-shape of its EPR spectrum. However, by deleting the free radical signal I from the EPR spectra of reduced Centre A alone or both Centres A plus B reduced, it was possible to double integrate these spectra to demonstrate that Centre B is present in the Photosystem I reaction centre in amounts comparable to those of Centre A and thus also signal I (P-700) and X. Oxidation-reduction potential titrations confirmed that Centre A had Em congruent to -550 mV, Centre B had Em congruent to -585 mV. These results, and those presented for the photoreduction of Centre B, place Centre B before Centre A in the sequence of electron transport in Photosystem I particles at cryogenic temperatures. When both A and B are reduced, P-700 photooxidation is reversible at low temperature and coupled to the reduction of the component X. The change from irreversible to reversible P-700 photooxidation and the photoreduction of X showed the same potential dependence as the reduction of Centre B with Em congruent to -585 mV, substantiating the identification of X as the primary electron acceptor of Photosystem I.", "contents": "The role of the membrane-bound iron-sulphur centres A and B in the photosystem I reaction centre of spinach chloroplasts. Photosystem I particles prepared from spinach chloroplast using Triton X-100 were frozen in the dark with the bound iron-sulphur Centre A reduced. Illumination at cryogenic temperatures of such samples demonstrated the photoreduction of the second bound iron-sulphur Centre B. Due to electron spin-electron spin interaction between these two bound iron-sulphur centres, it was not possible to quantify amounts of Centre B relative to the other components of the Photosystem I reaction centre by simulating the line-shape of its EPR spectrum. However, by deleting the free radical signal I from the EPR spectra of reduced Centre A alone or both Centres A plus B reduced, it was possible to double integrate these spectra to demonstrate that Centre B is present in the Photosystem I reaction centre in amounts comparable to those of Centre A and thus also signal I (P-700) and X. Oxidation-reduction potential titrations confirmed that Centre A had Em congruent to -550 mV, Centre B had Em congruent to -585 mV. These results, and those presented for the photoreduction of Centre B, place Centre B before Centre A in the sequence of electron transport in Photosystem I particles at cryogenic temperatures. When both A and B are reduced, P-700 photooxidation is reversible at low temperature and coupled to the reduction of the component X. The change from irreversible to reversible P-700 photooxidation and the photoreduction of X showed the same potential dependence as the reduction of Centre B with Em congruent to -585 mV, substantiating the identification of X as the primary electron acceptor of Photosystem I."}
{"id": "PMID:210804", "title": "Kinetic studies on oxidized and partially reduced cytochrome c oxidase.", "content": "1. Kinetic studies have been performed with beef-heart cytochrome c oxidase, with the enzyme either in its oxidized, resting state or pretreated anaerobically with different amounts of reduced cytochrome c. The techniques used for the study have been stopped-flow spectrophotometry and electron paramagnetic resonance (EPR) spectroscopy. 2. The results show that the one-electron equivalent-reduced enzyme rapidly oxidizes one further equivalent of aerobically or anaerobically added ferrocytochrome c, with a rate constant of 5 . 10(6) M-1 . s-1. 3. When an excess of ferrocytochrome c in the presence of oxygen is added to the one-electron-reduced enzyme, the same turnover rate is obtained as in experiments with the resting enzyme. 4. The one-electron equivalent-enzyme reacts with CO with a rate constant of 4 . 10(4) M-1 . s-1 to yield approx. 35% of the CO compound as compared with the reaction between the fully reduced enzyme and CO. 5. It is shown that on reduction the enzyme is converted into an active form, but it is concluded that the enzyme does not have to be fully reduced before it is catalytically active.", "contents": "Kinetic studies on oxidized and partially reduced cytochrome c oxidase. 1. Kinetic studies have been performed with beef-heart cytochrome c oxidase, with the enzyme either in its oxidized, resting state or pretreated anaerobically with different amounts of reduced cytochrome c. The techniques used for the study have been stopped-flow spectrophotometry and electron paramagnetic resonance (EPR) spectroscopy. 2. The results show that the one-electron equivalent-reduced enzyme rapidly oxidizes one further equivalent of aerobically or anaerobically added ferrocytochrome c, with a rate constant of 5 . 10(6) M-1 . s-1. 3. When an excess of ferrocytochrome c in the presence of oxygen is added to the one-electron-reduced enzyme, the same turnover rate is obtained as in experiments with the resting enzyme. 4. The one-electron equivalent-enzyme reacts with CO with a rate constant of 4 . 10(4) M-1 . s-1 to yield approx. 35% of the CO compound as compared with the reaction between the fully reduced enzyme and CO. 5. It is shown that on reduction the enzyme is converted into an active form, but it is concluded that the enzyme does not have to be fully reduced before it is catalytically active."}
{"id": "PMID:210805", "title": "Do copper ions influence the reduction of ferricytochrome C by O-2?", "content": "Recently, it was suggested that the measured rate of reduction of ferricytochrome C by O-2 below pH 8, was too high in the presence of high concentrations of formate (Koppenol, W.H., Van Buuren, K.J.H., Butler J. and Braams, R. (1976) Biochim. Biophys. Acta 449, 157-168). The high values were attributed to the presence of impurities of copper, which compete for O-2. This assumption is consistent with either a decrease in the reduction yield of ferricytochrome C in the presence of copper, or with a very fast reaction of Cu(I) with ferricytochrome C. It was previously shown by us and by others that the reduction yield of ferricytochrome C by O-2 IS 100%. We measured the rate of reduction of ferricytochrome C by Cu(I), and found that this reaction is slow: k = (1.5 +/- 0.5) . 10(3) M-1 . s-1. Therefore, our results rule out the possibility that below pH 8 copper impurities affect the measured rate constant of the reduction of ferricytochrome C by O-2.", "contents": "Do copper ions influence the reduction of ferricytochrome C by O-2? Recently, it was suggested that the measured rate of reduction of ferricytochrome C by O-2 below pH 8, was too high in the presence of high concentrations of formate (Koppenol, W.H., Van Buuren, K.J.H., Butler J. and Braams, R. (1976) Biochim. Biophys. Acta 449, 157-168). The high values were attributed to the presence of impurities of copper, which compete for O-2. This assumption is consistent with either a decrease in the reduction yield of ferricytochrome C in the presence of copper, or with a very fast reaction of Cu(I) with ferricytochrome C. It was previously shown by us and by others that the reduction yield of ferricytochrome C by O-2 IS 100%. We measured the rate of reduction of ferricytochrome C by Cu(I), and found that this reaction is slow: k = (1.5 +/- 0.5) . 10(3) M-1 . s-1. Therefore, our results rule out the possibility that below pH 8 copper impurities affect the measured rate constant of the reduction of ferricytochrome C by O-2."}
{"id": "PMID:210806", "title": "Chaotropic resolution of high molecular weight (type I) NADH dehydrogenase, and reassociation of flavin-rich (type II) and flavin-poor subunits.", "content": "1. Type-I NADH dehydrogenase (Complex I) was solubilized and dissociated into subunits by NaClO4. NADH slows the dissociation. On subsequent stepwise addition of (NH4)2SO4 the dissociation is partly reversed, as is to be expected from the opposing effects of ClO-4 and SO-24, which are on the salting-in and salting-out sides, respectively, of the lyotropic series. 2. In consequence, the aggregates of subunits that are separated by (NH4)2-SO4 fractionation consist of randomly associated subunits as well as fragments of Type I enzyme. The fraction precipitating at 27% satd. (NH4)2SO4 is flavin-poor, that remaining soluble at 55% satd. (NH4)2SO4 flavin-rich and those separating between 27 and 55% satd. (NH4)2SO4 intermediate in composition. 3. The fraction remaining soluble at 55% satd. (NH4)2SO4 contains the purified low-molecular-weight iron-sulphur flavoprotein (Type-II dehydrogenase). It is a dimer consisting of one molecule of FMN, one 28-kilodalton and one 56-kilodalton subunit per protomer. Work of others indicates that it contains 4 Fe and 4 acid-labile S atoms per molecule of FMN. Sometimes the fraction remaining soluble at 55% satd. (NH4)2SO4 contained an additional small subunit (12 kilodaltons) and four additional Fe and acid labile S atoms per protomer. The sedimentation coefficients (s020,w) of the two preparations were 5.3 and 6.6 S, respectively, with calculated frictional ratios of 1.5 and 1.24, respectively. 4. The intermediate fractions are mixtures of the various subunits present in Complex I. Specifically a fraction separating at 55% satd. (NH4)2SO4 was found to be a mixture of two fragments, the pure iron-sulphur flavoprotein and a 26-S fragment that contained per protomer four subunits of 12 kilodaltons, one each of 28, 32, 56 and 77 kilodaltons, one molecule of FMN and 20 Fe and acid-labile S atoms. It was probably tetrameric or even larger. 5. The oxidoreductase activity of the intermediate fractions is dependent on the protein concentration, the activity with ferricyanide increasing and that with ferricytochrome c decreasing with increasing protein concentration. This is interpreted as  an increased association of subunits present in the intermediate fractions. Similar results are obtained when flavin-rich and flavin-poor fractions are mixed. The association is cooperative. NADH favours the association of the subunits. 6. Association of the subunits is accompanied by a 10-fold increase in k2 (rate constant for intramolecular electron flow), a 10-fold decrease of the accessibility of ferricyanide to the reduced enzyme and a 10(4)-fold decrease of the accessibility of ferricytochrome c. The Ks (NADH) is also decreased. Although the changes are in the direction to be expected from a conversion of Type II enzyme to Type I, the value of k2 is still much less than in the latter enzyme.", "contents": "Chaotropic resolution of high molecular weight (type I) NADH dehydrogenase, and reassociation of flavin-rich (type II) and flavin-poor subunits. 1. Type-I NADH dehydrogenase (Complex I) was solubilized and dissociated into subunits by NaClO4. NADH slows the dissociation. On subsequent stepwise addition of (NH4)2SO4 the dissociation is partly reversed, as is to be expected from the opposing effects of ClO-4 and SO-24, which are on the salting-in and salting-out sides, respectively, of the lyotropic series. 2. In consequence, the aggregates of subunits that are separated by (NH4)2-SO4 fractionation consist of randomly associated subunits as well as fragments of Type I enzyme. The fraction precipitating at 27% satd. (NH4)2SO4 is flavin-poor, that remaining soluble at 55% satd. (NH4)2SO4 flavin-rich and those separating between 27 and 55% satd. (NH4)2SO4 intermediate in composition. 3. The fraction remaining soluble at 55% satd. (NH4)2SO4 contains the purified low-molecular-weight iron-sulphur flavoprotein (Type-II dehydrogenase). It is a dimer consisting of one molecule of FMN, one 28-kilodalton and one 56-kilodalton subunit per protomer. Work of others indicates that it contains 4 Fe and 4 acid-labile S atoms per molecule of FMN. Sometimes the fraction remaining soluble at 55% satd. (NH4)2SO4 contained an additional small subunit (12 kilodaltons) and four additional Fe and acid labile S atoms per protomer. The sedimentation coefficients (s020,w) of the two preparations were 5.3 and 6.6 S, respectively, with calculated frictional ratios of 1.5 and 1.24, respectively. 4. The intermediate fractions are mixtures of the various subunits present in Complex I. Specifically a fraction separating at 55% satd. (NH4)2SO4 was found to be a mixture of two fragments, the pure iron-sulphur flavoprotein and a 26-S fragment that contained per protomer four subunits of 12 kilodaltons, one each of 28, 32, 56 and 77 kilodaltons, one molecule of FMN and 20 Fe and acid-labile S atoms. It was probably tetrameric or even larger. 5. The oxidoreductase activity of the intermediate fractions is dependent on the protein concentration, the activity with ferricyanide increasing and that with ferricytochrome c decreasing with increasing protein concentration. This is interpreted as  an increased association of subunits present in the intermediate fractions. Similar results are obtained when flavin-rich and flavin-poor fractions are mixed. The association is cooperative. NADH favours the association of the subunits. 6. Association of the subunits is accompanied by a 10-fold increase in k2 (rate constant for intramolecular electron flow), a 10-fold decrease of the accessibility of ferricyanide to the reduced enzyme and a 10(4)-fold decrease of the accessibility of ferricytochrome c. The Ks (NADH) is also decreased. Although the changes are in the direction to be expected from a conversion of Type II enzyme to Type I, the value of k2 is still much less than in the latter enzyme."}
{"id": "PMID:210807", "title": "The electric potential field around cytochrome c and the effect of ionic strength on reaction rates of horse cytochrome c.", "content": "1. The electric potential fields around tuna ferri- and ferrocytochrome c were calculated assuming that (i) all of the lysines and arginines are protonated, (ii) all of the glutamic and aspartic acids and the terminal carboxylic acid are dissociated, and (iii) the haem has a net charge of +1e in the oxidized form. 2. Near the haem crevice high values for the potential (greater than +2.5 kT/e) are found. Consequently, electron transfer via the haem edge is favored if the oxidant or reductant is negatively charged. 3. The inhomogeneous distribution of charges leads to a dipole moment of 244 and 238 debye for oxidized and reduced tuna cytochrome c, respectively. Horse cytochrome c has dipole moments of 303 (oxidized) and 286 (reduced) debye. 4. A line through the positive and negative charge centres, the dipole axis, crosses the tuna cytochrome c surface at Ala 83 (positive part) and Lys 99 (negative part). The direction of the dipole axis of horse cytochrome c is very similar. Since the centre of the domain on the cytochrome c surface, which is involved in the binding to cytochrome c oxidase, is found at the beta-carbon of the Phe 82 in horse cytochrome c (Ferguson-Miller, S., Brautigan, D.L. and Margoliash, E. (1978) J. Biol. Chem. 253, 149--159) it is suggested that the direction of the dipole is of physiological importance. 5. The activity coefficients of horse ferri- and ferrocytochrome c were calculated as a function of ionic strength using a formula derived by Kirkwood (Kirkwood, J.G. (1934) J. Chem. Phys. 2, 351--361). 6. Due to the high net charge at pH 7.5 the influence of the dipole moments of horse ferri- and ferrocytochrome c on the respective activity coefficients can be neglected at I less than or equal to 50 mM. 7. Using the Br\u00f8nsted relation the effect of ionic strength on reaction rates of horse cytochrome c was calculated. Good agreement is found between theory and experimental results reported in the literature.", "contents": "The electric potential field around cytochrome c and the effect of ionic strength on reaction rates of horse cytochrome c. 1. The electric potential fields around tuna ferri- and ferrocytochrome c were calculated assuming that (i) all of the lysines and arginines are protonated, (ii) all of the glutamic and aspartic acids and the terminal carboxylic acid are dissociated, and (iii) the haem has a net charge of +1e in the oxidized form. 2. Near the haem crevice high values for the potential (greater than +2.5 kT/e) are found. Consequently, electron transfer via the haem edge is favored if the oxidant or reductant is negatively charged. 3. The inhomogeneous distribution of charges leads to a dipole moment of 244 and 238 debye for oxidized and reduced tuna cytochrome c, respectively. Horse cytochrome c has dipole moments of 303 (oxidized) and 286 (reduced) debye. 4. A line through the positive and negative charge centres, the dipole axis, crosses the tuna cytochrome c surface at Ala 83 (positive part) and Lys 99 (negative part). The direction of the dipole axis of horse cytochrome c is very similar. Since the centre of the domain on the cytochrome c surface, which is involved in the binding to cytochrome c oxidase, is found at the beta-carbon of the Phe 82 in horse cytochrome c (Ferguson-Miller, S., Brautigan, D.L. and Margoliash, E. (1978) J. Biol. Chem. 253, 149--159) it is suggested that the direction of the dipole is of physiological importance. 5. The activity coefficients of horse ferri- and ferrocytochrome c were calculated as a function of ionic strength using a formula derived by Kirkwood (Kirkwood, J.G. (1934) J. Chem. Phys. 2, 351--361). 6. Due to the high net charge at pH 7.5 the influence of the dipole moments of horse ferri- and ferrocytochrome c on the respective activity coefficients can be neglected at I less than or equal to 50 mM. 7. Using the Br\u00f8nsted relation the effect of ionic strength on reaction rates of horse cytochrome c was calculated. Good agreement is found between theory and experimental results reported in the literature."}
{"id": "PMID:210808", "title": "Structural organization of the Chromatium vinosum reaction center associated c-cytochromes.", "content": "Magnetic interactions operating between the Chromatium vinosum reaction center associated c-cytochromes and the electron carriers of the reaction center have been assayed by comparing the magnetic properties of these components alone, and in various combinations with paramagnetic forms of the reaction center electron carriers. These studies have yielded the following results. 1. The oxidized paramagnetic forms of the high potential cytochromes c-555 produce no discernable alteration of the light-induced (BChl)2.+signal. 2. Similarly, analysis of the lineshape of the light-induced (BChl)2.+signal shows that a magnetic interaction with the oxidized low potential cytochromes c-553 is likely to produce less than a 1 gauss splitting of the (BChl)2.+signal, which corresponds to a minimum separation of 25 +/- 3 A between the unpaired spins if the heme and (BChl)2 are orientated in a coplanar arrangement, suggesting a minimum separation of 15+/- 3A between the heme edge and the (BChl)2 edge. 3. a prominent magnetic interaction is observed to operate between the cytochrome c-553 and c-555, which results in a 30-35 gauss splitting of these spectra, and suggests an iron to iron separation of about 8 A.4. Magnetic interactions are not observed between the c-cytochromes and the reaction center \"primary acceptor\" (the iron . quinone complex) nor with the reaction center intermediate electron carrier (which involves bacteriopheophytin) suggesting separations greater than 10 A. 5. Magnetic interactions are not discerned between the two cytochrome c-553 hemes, nor between the two cytochrome c-555 hemes, implying that the distance between the cytochromes of the same pair is greater than 10 A. 6. EPR studies of oriented chromatophores have demonstrated that the cytochrome c-553 and c-555 hemes are perpendicular to each other, and suggest that the cytochrome c-553 heme plane lies parallel to the plane of the membrane, while the cytochrome c-555 heme plane lies perpendicular to the plane of the membrane surface.", "contents": "Structural organization of the Chromatium vinosum reaction center associated c-cytochromes. Magnetic interactions operating between the Chromatium vinosum reaction center associated c-cytochromes and the electron carriers of the reaction center have been assayed by comparing the magnetic properties of these components alone, and in various combinations with paramagnetic forms of the reaction center electron carriers. These studies have yielded the following results. 1. The oxidized paramagnetic forms of the high potential cytochromes c-555 produce no discernable alteration of the light-induced (BChl)2.+signal. 2. Similarly, analysis of the lineshape of the light-induced (BChl)2.+signal shows that a magnetic interaction with the oxidized low potential cytochromes c-553 is likely to produce less than a 1 gauss splitting of the (BChl)2.+signal, which corresponds to a minimum separation of 25 +/- 3 A between the unpaired spins if the heme and (BChl)2 are orientated in a coplanar arrangement, suggesting a minimum separation of 15+/- 3A between the heme edge and the (BChl)2 edge. 3. a prominent magnetic interaction is observed to operate between the cytochrome c-553 and c-555, which results in a 30-35 gauss splitting of these spectra, and suggests an iron to iron separation of about 8 A.4. Magnetic interactions are not observed between the c-cytochromes and the reaction center \"primary acceptor\" (the iron . quinone complex) nor with the reaction center intermediate electron carrier (which involves bacteriopheophytin) suggesting separations greater than 10 A. 5. Magnetic interactions are not discerned between the two cytochrome c-553 hemes, nor between the two cytochrome c-555 hemes, implying that the distance between the cytochromes of the same pair is greater than 10 A. 6. EPR studies of oriented chromatophores have demonstrated that the cytochrome c-553 and c-555 hemes are perpendicular to each other, and suggest that the cytochrome c-553 heme plane lies parallel to the plane of the membrane, while the cytochrome c-555 heme plane lies perpendicular to the plane of the membrane surface."}
{"id": "PMID:210811", "title": "Elementary steps of the (Na+ + K+)-ATPase mechanism, studied with formycin nucleotides.", "content": "1. Formycin triphosphate (FTP), a fluorescent analogue of ATP, is a substrate for (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3), with properties similar to those of ATP. 2. FTP and formycin diphosphate (FDP) bind to the enzyme with high affinity and, on binding, the nucleotide fluorescence is enhanced 3-4-fold. It is therefore possible, with a stopped-flow fluorimeter, to measure the rates of binding and release of FTP and FDP under conditions in which turnover does not occur. 3. When the enzyme-FTP complex is exposed to conditions permitting turnover (Mg2+, Na+ +/- K+), changes in fluorescence occur which can be explained by supposing that they reflect the interconversion of states with or without bound nucleotides. A rapid fall in fluorescence, that we attribute to the rapid release of FDP from newly phosphorylated enzyme, is followed by a steady state in which low fluorescence suggests that little nucleotide is bound. Eventually, exhaustion of FTP allows rebinding of FDP to the enzyme, which is signalled by a rise in fluorescence. 4. The estimated rate of FDP release from newly formed phosphoenzyme is unaffected by the presence of K+ (0-2 mM) or the concentration of FTP (1-20 micron). 5. Experiments with [gamma-32P]FTP show that about 1 mol of 32P is incorporated per mol of enzyme. The rate of phosphorylation of the enzyme by [gamma-32P]FTP has been measured with a rapid-mixing-and-quenching apparatus. 6. Kinetic data from the fluorescence and phosphorylation experiments show that the behaviour of the enzyme, at least at the low nucleotide concentrations employed, is consistent with the Albers-Post model, and is difficult to reconcile with models in which K+ acts at or before the step in which FDP is released during turnover.", "contents": "Elementary steps of the (Na+ + K+)-ATPase mechanism, studied with formycin nucleotides. 1. Formycin triphosphate (FTP), a fluorescent analogue of ATP, is a substrate for (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3), with properties similar to those of ATP. 2. FTP and formycin diphosphate (FDP) bind to the enzyme with high affinity and, on binding, the nucleotide fluorescence is enhanced 3-4-fold. It is therefore possible, with a stopped-flow fluorimeter, to measure the rates of binding and release of FTP and FDP under conditions in which turnover does not occur. 3. When the enzyme-FTP complex is exposed to conditions permitting turnover (Mg2+, Na+ +/- K+), changes in fluorescence occur which can be explained by supposing that they reflect the interconversion of states with or without bound nucleotides. A rapid fall in fluorescence, that we attribute to the rapid release of FDP from newly phosphorylated enzyme, is followed by a steady state in which low fluorescence suggests that little nucleotide is bound. Eventually, exhaustion of FTP allows rebinding of FDP to the enzyme, which is signalled by a rise in fluorescence. 4. The estimated rate of FDP release from newly formed phosphoenzyme is unaffected by the presence of K+ (0-2 mM) or the concentration of FTP (1-20 micron). 5. Experiments with [gamma-32P]FTP show that about 1 mol of 32P is incorporated per mol of enzyme. The rate of phosphorylation of the enzyme by [gamma-32P]FTP has been measured with a rapid-mixing-and-quenching apparatus. 6. Kinetic data from the fluorescence and phosphorylation experiments show that the behaviour of the enzyme, at least at the low nucleotide concentrations employed, is consistent with the Albers-Post model, and is difficult to reconcile with models in which K+ acts at or before the step in which FDP is released during turnover."}
{"id": "PMID:210812", "title": "Conformational transitions between Na+-bound and K+-bound forms of (Na+ + K+)-ATPase, studied with formycin nucleotides.", "content": "1. Fluorescence measurements have shown that formycin triphosphate (FTP) or formycin diphosphate (FDP) bound to (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) in Na+-containing media can be displaced by the following ions (listed in order of effectiveness): Tl+, K+, Rb+, NH4+, Cs+. 2. The differences between the nucleotide affinities displayed by the enzyme in predominantly Na+ and predominantly K+ media in the absence of phosphorylation, are thought to reflect changes in enzyme conformation. These changes can therefore be monitored by observing the changes in fluorescence that accompany net binding or net release of formycin nucleotides. 3. The transition from a K+-bound form (E2-(K)) to an Na+-bound form (E1-Na) is remarkably slow at low nucleotide concentrations, but is accelerated if the nucleotide concentration is increased. This suggests that the binding of nucleotide to a low-affinity site on E2-(K) accelerates its conversion to E1-Na; it supports the hypothesis that during the normal working of the pump, ATP, acting at a low affinity site, accelerates the conversion of dephosphoenzyme, newly formed by K+-catalysed hydrolysis of E2P, to a form in which it can be phosphorylated in the presence of Na+. 4. The rate of the reverse transformation, E1-Na to E2-(K), varies roughly linearly with the K+ concentration up to the highest concentration at which the rate can be measured (15 mM). Since much lower concentrations of K+ are sufficient to displace the equilibrium to the K-form, we suggest that the sequence of events is: (i) combination of K+ with low affinity (probably internal) binding sites, followed by (ii) spontaneous conversion of the enzyme to a form, E2-(K), containing occluded K+. 5. Mg2+ or oligomycin slows the rate of conversion of E1-Na to E2-(K) but does not significantly affect the rate of conversion of E2-(K) to E1-Na. 6. In the light of these and previous findings, we propose a model for the sodium pump in which conformational changes alternate with trans-phosphorylations, and the inward and outward fluxes of both Na+ and K+ each involve the transfer of a phosphoryl group as well as a change in conformation between E1 and E2 forms of the enzyme or phosphoenzyme.", "contents": "Conformational transitions between Na+-bound and K+-bound forms of (Na+ + K+)-ATPase, studied with formycin nucleotides. 1. Fluorescence measurements have shown that formycin triphosphate (FTP) or formycin diphosphate (FDP) bound to (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) in Na+-containing media can be displaced by the following ions (listed in order of effectiveness): Tl+, K+, Rb+, NH4+, Cs+. 2. The differences between the nucleotide affinities displayed by the enzyme in predominantly Na+ and predominantly K+ media in the absence of phosphorylation, are thought to reflect changes in enzyme conformation. These changes can therefore be monitored by observing the changes in fluorescence that accompany net binding or net release of formycin nucleotides. 3. The transition from a K+-bound form (E2-(K)) to an Na+-bound form (E1-Na) is remarkably slow at low nucleotide concentrations, but is accelerated if the nucleotide concentration is increased. This suggests that the binding of nucleotide to a low-affinity site on E2-(K) accelerates its conversion to E1-Na; it supports the hypothesis that during the normal working of the pump, ATP, acting at a low affinity site, accelerates the conversion of dephosphoenzyme, newly formed by K+-catalysed hydrolysis of E2P, to a form in which it can be phosphorylated in the presence of Na+. 4. The rate of the reverse transformation, E1-Na to E2-(K), varies roughly linearly with the K+ concentration up to the highest concentration at which the rate can be measured (15 mM). Since much lower concentrations of K+ are sufficient to displace the equilibrium to the K-form, we suggest that the sequence of events is: (i) combination of K+ with low affinity (probably internal) binding sites, followed by (ii) spontaneous conversion of the enzyme to a form, E2-(K), containing occluded K+. 5. Mg2+ or oligomycin slows the rate of conversion of E1-Na to E2-(K) but does not significantly affect the rate of conversion of E2-(K) to E1-Na. 6. In the light of these and previous findings, we propose a model for the sodium pump in which conformational changes alternate with trans-phosphorylations, and the inward and outward fluxes of both Na+ and K+ each involve the transfer of a phosphoryl group as well as a change in conformation between E1 and E2 forms of the enzyme or phosphoenzyme."}
{"id": "PMID:210813", "title": "Affinity purification and some properties of nucleoside diphosphatase from rat liver cytosol.", "content": "Nucleosidediphosphatase (nucleosidediphosphate phosphohydrolase, EC 3.6.1.6) of rat liver cytosol was purified up to 336--fold by the procedure including affinity chromatographies of concanavalin A- and alanine-Sepharose. The final purified enzyme showed a single protein band upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Its native form was found to be a tetramer with molecular weight of 120 000 which consists of subunit with molecular weight of 30 000. The enzyme was found to be a glycoprotein on the basis of its chromatographic behaviour with concanavalin A-Sepharose and positive staining with periodate-Schiff reaction in polyacrylamide gels. Furthermore, the two molecular forms with isoelectric points of 4.7 and 5.0 were demonstrated by electrofocusing, though they did not show any significant difference with respect to their catalytic properties.", "contents": "Affinity purification and some properties of nucleoside diphosphatase from rat liver cytosol. Nucleosidediphosphatase (nucleosidediphosphate phosphohydrolase, EC 3.6.1.6) of rat liver cytosol was purified up to 336--fold by the procedure including affinity chromatographies of concanavalin A- and alanine-Sepharose. The final purified enzyme showed a single protein band upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Its native form was found to be a tetramer with molecular weight of 120 000 which consists of subunit with molecular weight of 30 000. The enzyme was found to be a glycoprotein on the basis of its chromatographic behaviour with concanavalin A-Sepharose and positive staining with periodate-Schiff reaction in polyacrylamide gels. Furthermore, the two molecular forms with isoelectric points of 4.7 and 5.0 were demonstrated by electrofocusing, though they did not show any significant difference with respect to their catalytic properties."}
{"id": "PMID:210814", "title": "Use of methanethiolation to investigate the catalytic role of sulphydryl groups in rabbit skeletal muscle pyruvate kinase.", "content": "Incubation of rabbit skeletal muscle pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) with methyl methanethiosulphonate resulted in the time- and inhibitor concentration-dependent loss of enzyme activity. Substrates or products of the catalytic reaction prevented the loss of activity caused by methanethiolation. Their effectiveness as protecting agents was placed in the order ADP greater than ATP greater than Mg2+ greater than phosphoenolpyruvate greater than pyruvate. The essential catalytic cation, K+, had no effect on the methanethiolation reaction. [Me-3H]Methanethiosulphonate modified all the available cysteine thiol groups which correlated to the incorporation of four SC3H3 groups per protomer. Four radioactive peptides were obtained on tryptic peptide mapping. When methanethiolation was carried out in the presence of Mg2+ alone or with Mg2+ and ATP together, then only three SC3H3 groups were incorporated into each subunit. If MgATP protected methanethiolated pyruvate kinase was reacted with iodo[2-3H]acetic acid then 1.37 +/- 0.2 groups per protomer were carboxymethylated. 70% of the radioactivity was located in a single peptide on tryptic peptide mapping. This peptide was isolated and contained the segment carboxymethyl cysteine (Glx, Asx, Ser) Arg. Collectively these data indicate that although all thiol groups are equally accessible to methyl methanethiosulphonate, only a single thiol group participates in the catalytic event. An additional role in the maintenance of structure for this thiol group was also shown in studied of reduction and thermal denaturation of the enzyme.", "contents": "Use of methanethiolation to investigate the catalytic role of sulphydryl groups in rabbit skeletal muscle pyruvate kinase. Incubation of rabbit skeletal muscle pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) with methyl methanethiosulphonate resulted in the time- and inhibitor concentration-dependent loss of enzyme activity. Substrates or products of the catalytic reaction prevented the loss of activity caused by methanethiolation. Their effectiveness as protecting agents was placed in the order ADP greater than ATP greater than Mg2+ greater than phosphoenolpyruvate greater than pyruvate. The essential catalytic cation, K+, had no effect on the methanethiolation reaction. [Me-3H]Methanethiosulphonate modified all the available cysteine thiol groups which correlated to the incorporation of four SC3H3 groups per protomer. Four radioactive peptides were obtained on tryptic peptide mapping. When methanethiolation was carried out in the presence of Mg2+ alone or with Mg2+ and ATP together, then only three SC3H3 groups were incorporated into each subunit. If MgATP protected methanethiolated pyruvate kinase was reacted with iodo[2-3H]acetic acid then 1.37 +/- 0.2 groups per protomer were carboxymethylated. 70% of the radioactivity was located in a single peptide on tryptic peptide mapping. This peptide was isolated and contained the segment carboxymethyl cysteine (Glx, Asx, Ser) Arg. Collectively these data indicate that although all thiol groups are equally accessible to methyl methanethiosulphonate, only a single thiol group participates in the catalytic event. An additional role in the maintenance of structure for this thiol group was also shown in studied of reduction and thermal denaturation of the enzyme."}
{"id": "PMID:210815", "title": "Studies on the mechanism of inhibition of redox enzymes by substituted hydroxamic acids.", "content": "Substituted primary hydroxamic acids were found to inhibit the catalytic activity of a number of redox enzymes. The inhibition was not related to the nature of the metal-active site of the enzyme nor to the nature of the oxygen-containing substrate. Two easily available enzymes, mushroom tyrosinase (monophenol,dihydroyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) and horseradish peroxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7), which were potently inhibited by hydroxamic acids, were chosen for more detailed study. A kinetic analysis of the inhibitory effects on the partially purified tyrosinase of mushroom (Agaricus bispora) revealed that inhibition was reversible and competiitive with respect to reducing substrate concentration, but was not competitive with respect to molecular oxygen concentration. A spectrophotometric and EPR study of the binding of salicylhydroxamic acid to horseradish peroxidase revealed that his hydroxamic acid was bound to the enzyme in the same manner as a typical substrate, hydroquinone. Spectroscopic and thermodynamic measurements of the binding reactions suggested that this binding site is close, to but, not directly onto, the heme group of the enzyme. From these results it is concluded that the mode of inhibition of hydroxamic acid need not be, as generally supposed, by metal chelation, and mechanisms involving either hydrogen bonding at the reducing substrate binding site or the formation of a charge transfer complex between hydroxamic acid and an electron-accepting group in the enzyme are considered to be more feasible. The relevance of these findings to deductions on the nature of other hydroxamic acid-inhibitable systems is discussed.", "contents": "Studies on the mechanism of inhibition of redox enzymes by substituted hydroxamic acids. Substituted primary hydroxamic acids were found to inhibit the catalytic activity of a number of redox enzymes. The inhibition was not related to the nature of the metal-active site of the enzyme nor to the nature of the oxygen-containing substrate. Two easily available enzymes, mushroom tyrosinase (monophenol,dihydroyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) and horseradish peroxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7), which were potently inhibited by hydroxamic acids, were chosen for more detailed study. A kinetic analysis of the inhibitory effects on the partially purified tyrosinase of mushroom (Agaricus bispora) revealed that inhibition was reversible and competiitive with respect to reducing substrate concentration, but was not competitive with respect to molecular oxygen concentration. A spectrophotometric and EPR study of the binding of salicylhydroxamic acid to horseradish peroxidase revealed that his hydroxamic acid was bound to the enzyme in the same manner as a typical substrate, hydroquinone. Spectroscopic and thermodynamic measurements of the binding reactions suggested that this binding site is close, to but, not directly onto, the heme group of the enzyme. From these results it is concluded that the mode of inhibition of hydroxamic acid need not be, as generally supposed, by metal chelation, and mechanisms involving either hydrogen bonding at the reducing substrate binding site or the formation of a charge transfer complex between hydroxamic acid and an electron-accepting group in the enzyme are considered to be more feasible. The relevance of these findings to deductions on the nature of other hydroxamic acid-inhibitable systems is discussed."}
{"id": "PMID:210816", "title": "Inhibition of T4 polynucleotide kinase by the ATP analog, beta, gamma-imidoadenylyl 5'-triphosphate.", "content": "The inhibition of T4 polynucleotide kinase by beta,gamma-imidoadenylyl 5'-triphosphate has been investigated. It was found that the ATP analog was a competitive inhibitor with regard to ATP and a noncompetitive inhibitor with regard to DNA possessing a 5'-hydroxyl group. At pH 8.0, the Ki values were 3 and 11 mM, respectively. beta,gamma-imidoadenylyl 5'-triphosphate was not a substrate in the forward reaction, but would replace ADP and ATP in the reverse reaction. The reverse reaction was also used to make beta,gamma-imidoadenylyl 5'-tetraphosphate.", "contents": "Inhibition of T4 polynucleotide kinase by the ATP analog, beta, gamma-imidoadenylyl 5'-triphosphate. The inhibition of T4 polynucleotide kinase by beta,gamma-imidoadenylyl 5'-triphosphate has been investigated. It was found that the ATP analog was a competitive inhibitor with regard to ATP and a noncompetitive inhibitor with regard to DNA possessing a 5'-hydroxyl group. At pH 8.0, the Ki values were 3 and 11 mM, respectively. beta,gamma-imidoadenylyl 5'-triphosphate was not a substrate in the forward reaction, but would replace ADP and ATP in the reverse reaction. The reverse reaction was also used to make beta,gamma-imidoadenylyl 5'-tetraphosphate."}
{"id": "PMID:210817", "title": "Protamine-agarose non-charged alkyl derivatives of agarose in the purification of rat-liver phosphoprotein phosphatases.", "content": "1. Protamine-agarose and hydrophobic interaction chromatography were found to be effective in the purification of phosphoprotein  phosphatase(s) (phosphoprotein phosphohydrolase, EC 3.1.3.16) of rat-liver. The phosphoprotein phosphatase of rat-liver cytosol were first resolved into three fractions, termed A, B and C, in order of elution from DEAE-cellulose. Whereas all fractions displayed activity towards [32P]phosphoprotamine, only fractions B and C displayed appreciable activity towards [32P]phosphopyruvate kinase. Since fraction B exhibited the most properties and the highest recovery of enzymatic activity towards [32P]phosphoprotamine and [32P]phosphopyruvate kinase, it was selected for further purification. The method developed involves sequential chromatography of fraction B on Sephadex G-200, protamineagarose, histone-agarose and then again on Sephadex G-200 as a final step. A 400-fold enrichment in the phosphoprotamine phosphatase activity of fraction B was obtained. Purified fraction B also displayed substantial phosphatase activity towards [32P]phosphopyruvate kinase and [32P]phosphohistones. An apparent molecular weight of about 250 000 was estimated for purified fraction B on a calibrated Sephadex G-200 column. The present data indicate that rat-liver cytosol contains multiple forms of phosphoprotein phosphatases and suggest a technique which might be applied for the further purification of at least fraction B. 2. In a separate approach, a combination of pentyl-agarose and protamineagarose chromatography was shown to be a conbenient method for the enrichment (up to 20-fold of phosphoprotein phosphatase activity from crude liver extracts.", "contents": "Protamine-agarose non-charged alkyl derivatives of agarose in the purification of rat-liver phosphoprotein phosphatases. 1. Protamine-agarose and hydrophobic interaction chromatography were found to be effective in the purification of phosphoprotein  phosphatase(s) (phosphoprotein phosphohydrolase, EC 3.1.3.16) of rat-liver. The phosphoprotein phosphatase of rat-liver cytosol were first resolved into three fractions, termed A, B and C, in order of elution from DEAE-cellulose. Whereas all fractions displayed activity towards [32P]phosphoprotamine, only fractions B and C displayed appreciable activity towards [32P]phosphopyruvate kinase. Since fraction B exhibited the most properties and the highest recovery of enzymatic activity towards [32P]phosphoprotamine and [32P]phosphopyruvate kinase, it was selected for further purification. The method developed involves sequential chromatography of fraction B on Sephadex G-200, protamineagarose, histone-agarose and then again on Sephadex G-200 as a final step. A 400-fold enrichment in the phosphoprotamine phosphatase activity of fraction B was obtained. Purified fraction B also displayed substantial phosphatase activity towards [32P]phosphopyruvate kinase and [32P]phosphohistones. An apparent molecular weight of about 250 000 was estimated for purified fraction B on a calibrated Sephadex G-200 column. The present data indicate that rat-liver cytosol contains multiple forms of phosphoprotein phosphatases and suggest a technique which might be applied for the further purification of at least fraction B. 2. In a separate approach, a combination of pentyl-agarose and protamineagarose chromatography was shown to be a conbenient method for the enrichment (up to 20-fold of phosphoprotein phosphatase activity from crude liver extracts."}
{"id": "PMID:210818", "title": "Plasma alpha-galactosidase A:properties and comparisons with tissue alpha-galactosidases.", "content": "The human plasma form of alpha-galactosidase A (alpha-D-galactoside galactohydrolase, EC 3.2.1.22) was highly purified and exhibited apparent Km values of 1.9 mM with 4-methylumbelliferyl-alpha-D-galactopyranoside and 0.23 mM with globotriglycosylceramide. Its inhibition with myo-inositol (Ki = 0.29 M) was similar to that observed with alpha-galactosidase A from various tissues. The plasma form of this lysosomal enzyme has a lower molecular weight of 96 600, a lower pI of 3.7 and faster electrophoretic mobility in polyacrylamide gels than the enzyme obtained from human liver. These data and the increased pI obtained after neuraminidase treatment suggest that the plasma form is an isoenzyme with a more highly sialylated carbohydrate moiety than the tissue isoenzymes.", "contents": "Plasma alpha-galactosidase A:properties and comparisons with tissue alpha-galactosidases. The human plasma form of alpha-galactosidase A (alpha-D-galactoside galactohydrolase, EC 3.2.1.22) was highly purified and exhibited apparent Km values of 1.9 mM with 4-methylumbelliferyl-alpha-D-galactopyranoside and 0.23 mM with globotriglycosylceramide. Its inhibition with myo-inositol (Ki = 0.29 M) was similar to that observed with alpha-galactosidase A from various tissues. The plasma form of this lysosomal enzyme has a lower molecular weight of 96 600, a lower pI of 3.7 and faster electrophoretic mobility in polyacrylamide gels than the enzyme obtained from human liver. These data and the increased pI obtained after neuraminidase treatment suggest that the plasma form is an isoenzyme with a more highly sialylated carbohydrate moiety than the tissue isoenzymes."}
{"id": "PMID:210820", "title": "Effects of wheat germ agglutinin and concanavalin A on parameters of highly purified sodium-potassium adenosine triphosphatases from Squalus acanthias and Electrophorus electricus.", "content": "The effects of two lectins, wheat germ agglutinin and concanavalin A, were studied on a variety of parameters of two highly purified (Na+ + K+)-ATPases (ATP phosphohydrolase, EC 3.6.1.3), from the rectal salt gland of Squalus acanthias and from the electroplax of Electrophorus electricus. Both lectins agglutinated the rectal gland enzyme equally, but wheat germ agglutinin inhibited (Na+ + K+)-ATPase activity much more. The electroplax enzyme was only marginally agglutinated and inhibited by the lectins. Neuraminidase treatment of the rectal gland (Na+ + K+)-ATPase had no effect on germ agglutinin inhibition. The inhibition of the rectal gland (Na+ + K+)-ATPase by wheat germ agglutinin could be reversed by N,N'-diacetylchitobiose, which has a high affinity for wheat germ agglutinin. Neither ouabain inhibition nor ouabain binding to the rectal gland enzyme was affected by wheat germ agglutinin. The p-nitrophenylphosphatase activity of the rectal gland enzyme was not inhibited by wheat germ agglutinin. Na+-ATPase activity, which reflects ATP binding and phosphorylation at the substrate site was inhibited by wheat germ agglutinin and this inhibition was reversed by potassium. Evidence is cited (Pennington, J. and Hokin, L.E., in preparation) that the inhibition of the (Na+ + K+)-ATPase by wheat germ agglutinin is due to binding to the glycoprotein subunit.", "contents": "Effects of wheat germ agglutinin and concanavalin A on parameters of highly purified sodium-potassium adenosine triphosphatases from Squalus acanthias and Electrophorus electricus. The effects of two lectins, wheat germ agglutinin and concanavalin A, were studied on a variety of parameters of two highly purified (Na+ + K+)-ATPases (ATP phosphohydrolase, EC 3.6.1.3), from the rectal salt gland of Squalus acanthias and from the electroplax of Electrophorus electricus. Both lectins agglutinated the rectal gland enzyme equally, but wheat germ agglutinin inhibited (Na+ + K+)-ATPase activity much more. The electroplax enzyme was only marginally agglutinated and inhibited by the lectins. Neuraminidase treatment of the rectal gland (Na+ + K+)-ATPase had no effect on germ agglutinin inhibition. The inhibition of the rectal gland (Na+ + K+)-ATPase by wheat germ agglutinin could be reversed by N,N'-diacetylchitobiose, which has a high affinity for wheat germ agglutinin. Neither ouabain inhibition nor ouabain binding to the rectal gland enzyme was affected by wheat germ agglutinin. The p-nitrophenylphosphatase activity of the rectal gland enzyme was not inhibited by wheat germ agglutinin. Na+-ATPase activity, which reflects ATP binding and phosphorylation at the substrate site was inhibited by wheat germ agglutinin and this inhibition was reversed by potassium. Evidence is cited (Pennington, J. and Hokin, L.E., in preparation) that the inhibition of the (Na+ + K+)-ATPase by wheat germ agglutinin is due to binding to the glycoprotein subunit."}
{"id": "PMID:210821", "title": "Kinetics of inactivation and molecular asymmetry of NAD-specific glyceraldehyde-3-phosphate dehydrogenase of Pisum sativum.", "content": "Glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) has been purified to homogeneity from pea seeds. The purified enzyme gave a single protein band on polyacrylamide gel electrophoresis (with and without sodium dodecyl sulfate; subunit molecular weight 38 000). It is free from bound nucleotides. The kinetics of heat inactivation of the crude enzyme extract as well as the purified enzyme are biphasic, in that exactly half of the activity is destroyed more rapidly than the residual half. The data are consistent with the rate equation: (formula: (see text): where A0 and A are activities at times zero and t, respectively, and k1 and k2 are first-order rate constants for the fast and slow phases, respectively. Addition of NAD+ slows down thermal inactivation, without altering the overall kinetic pattern. The activity lost due to the fast component (k1) of the reaction is regained on colling ('annealing'), whereas the slow reaction (k2) is not reversed, suggesting the following scheme: formula (see text): This is confirmed by plotting the activity after 'annealing' against initial period of heating. A single first-order rate constant (k2) is observed. The enzyme possesses about one reactive SH group per subunit which can be titrated with 5,5'-dithio-bis-(2-nitrobenzoic acid). Blocking of these groups inactivates the enzyme. Inactivation with 20 micrometer N-ethylmaleimide and 30 micrometer iodoacetate (at pH 8.6 and 33 degrees C) follows simple first-order kinetics (rate constants 0.099 and 0.139 min-1, respectively), suggesting that all SH groups react equally readily with these reagents. Reaction of the enzyme with 0.6 micrometer p-chloromercuri benzoate, however, shows biphasic kinetics similar to thermal inactivation. The reaction of p-chloromercuri benzoate with partially heat-inactivated enzyme (residual activity 37.5%) follows simple first-order kinetics. The molecular asymmetry demonstrated by these results must arise from the unique quaternary structure of the enzyme molecule, which is apparently made up of chemically identical subunits (pseudo-isologous association).", "contents": "Kinetics of inactivation and molecular asymmetry of NAD-specific glyceraldehyde-3-phosphate dehydrogenase of Pisum sativum. Glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) has been purified to homogeneity from pea seeds. The purified enzyme gave a single protein band on polyacrylamide gel electrophoresis (with and without sodium dodecyl sulfate; subunit molecular weight 38 000). It is free from bound nucleotides. The kinetics of heat inactivation of the crude enzyme extract as well as the purified enzyme are biphasic, in that exactly half of the activity is destroyed more rapidly than the residual half. The data are consistent with the rate equation: (formula: (see text): where A0 and A are activities at times zero and t, respectively, and k1 and k2 are first-order rate constants for the fast and slow phases, respectively. Addition of NAD+ slows down thermal inactivation, without altering the overall kinetic pattern. The activity lost due to the fast component (k1) of the reaction is regained on colling ('annealing'), whereas the slow reaction (k2) is not reversed, suggesting the following scheme: formula (see text): This is confirmed by plotting the activity after 'annealing' against initial period of heating. A single first-order rate constant (k2) is observed. The enzyme possesses about one reactive SH group per subunit which can be titrated with 5,5'-dithio-bis-(2-nitrobenzoic acid). Blocking of these groups inactivates the enzyme. Inactivation with 20 micrometer N-ethylmaleimide and 30 micrometer iodoacetate (at pH 8.6 and 33 degrees C) follows simple first-order kinetics (rate constants 0.099 and 0.139 min-1, respectively), suggesting that all SH groups react equally readily with these reagents. Reaction of the enzyme with 0.6 micrometer p-chloromercuri benzoate, however, shows biphasic kinetics similar to thermal inactivation. The reaction of p-chloromercuri benzoate with partially heat-inactivated enzyme (residual activity 37.5%) follows simple first-order kinetics. The molecular asymmetry demonstrated by these results must arise from the unique quaternary structure of the enzyme molecule, which is apparently made up of chemically identical subunits (pseudo-isologous association)."}
{"id": "PMID:210822", "title": "Evidence for a role of sulfhydryl groups in catalytic activity and subunit interaction of the cyclic GMP-dependent protein kinase from silkworm.", "content": "Guanosine 3':5'-monophosphate-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) has been isolated from silkworm pupal fat body (Bombyx mori) which is devoid of any adenosine 3':5'-monophosphate-dependent protein kinase. The enzyme displayed catalytic properties which were roughly similar to those described for adenosine 3':5'-monophosphate-dependent protein kinase. This similarity has been found in substrate specificity, optimal Mg2+ dependency, polyamines effects and the lack of dependency upon sulfhydryl compound for activation by cyclic GMP. Treatment of the enzyme with sulfhydryl reagents, N-ethylmaleimide or p-chloromercuribenzoic acid, inhibited the catalytic activity as well as the dissociation of the binding and catalytic activities as shown by means of sucrose-density gradient ultracentrifugation. In the presence of cyclic GMP or histone, the disulfide-linked structure did not dissociate into separate subunits nor did it migrate as the holoenzyme but sedimented as an intermediate form carrying both binding and catalytic activities.", "contents": "Evidence for a role of sulfhydryl groups in catalytic activity and subunit interaction of the cyclic GMP-dependent protein kinase from silkworm. Guanosine 3':5'-monophosphate-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) has been isolated from silkworm pupal fat body (Bombyx mori) which is devoid of any adenosine 3':5'-monophosphate-dependent protein kinase. The enzyme displayed catalytic properties which were roughly similar to those described for adenosine 3':5'-monophosphate-dependent protein kinase. This similarity has been found in substrate specificity, optimal Mg2+ dependency, polyamines effects and the lack of dependency upon sulfhydryl compound for activation by cyclic GMP. Treatment of the enzyme with sulfhydryl reagents, N-ethylmaleimide or p-chloromercuribenzoic acid, inhibited the catalytic activity as well as the dissociation of the binding and catalytic activities as shown by means of sucrose-density gradient ultracentrifugation. In the presence of cyclic GMP or histone, the disulfide-linked structure did not dissociate into separate subunits nor did it migrate as the holoenzyme but sedimented as an intermediate form carrying both binding and catalytic activities."}
{"id": "PMID:210823", "title": "Preparation and properties of rabbit-muscle glyceraldehyde-phosphate dehydrogenase with equal binding parameters for the third and fourth NAD+ molecules.", "content": "1. A method of preparing rabbit-muscle glyceraldehyde-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) is described which yields a preparation differing in important respects from those previously described and resembling the enzyme isolated from sturgeon muscle. 2. Direct binding measurements at 25 degrees C by equilibrium gel filtration fit dissociation constants for the first two molecules that are too low to be measured by this technique and 0.9 micrometer for the third and fourth molecules. The dissociation constant of the fourth molecule is much lower than that previously reported for the rabbit-muscle enzyme. 3. In contrast to previous results with the rabbit-muscle enzyme, the increase in absorbance at 360 nm between three and four molecules of NAD+ bound to the enzyme was, within experimental error, the same as that with each of the first three molecules. 4. Data on the quenching of the protein fluorescence by NAD+ at 15 degrees C at different enzyme concentrations closely fit dissociation constants of 0.028 micrometer for the first two molecules and 0.27 micrometer for the third and fourth molecules.", "contents": "Preparation and properties of rabbit-muscle glyceraldehyde-phosphate dehydrogenase with equal binding parameters for the third and fourth NAD+ molecules. 1. A method of preparing rabbit-muscle glyceraldehyde-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12) is described which yields a preparation differing in important respects from those previously described and resembling the enzyme isolated from sturgeon muscle. 2. Direct binding measurements at 25 degrees C by equilibrium gel filtration fit dissociation constants for the first two molecules that are too low to be measured by this technique and 0.9 micrometer for the third and fourth molecules. The dissociation constant of the fourth molecule is much lower than that previously reported for the rabbit-muscle enzyme. 3. In contrast to previous results with the rabbit-muscle enzyme, the increase in absorbance at 360 nm between three and four molecules of NAD+ bound to the enzyme was, within experimental error, the same as that with each of the first three molecules. 4. Data on the quenching of the protein fluorescence by NAD+ at 15 degrees C at different enzyme concentrations closely fit dissociation constants of 0.028 micrometer for the first two molecules and 0.27 micrometer for the third and fourth molecules."}
{"id": "PMID:210824", "title": "Effects of polyamine hydrochlorides and salts on phosphoprotein phosphatase.", "content": "Polyamine hydrochlorides, NaCl and magnesium acetate stimulated the enzymatic dephosphorylation of phosphorylated H2B histone by two forms (large form, mol. wt. 250 000; small form, mol. wt. 30 000) of a pig heart phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16). These ionic compounds stimulated the large form of the enzyme 5--9-fold but stimulated the small form of theenzyme only 2-fold. With phosphorylated H2B histone as substrate, these effectors caused an increase in both Km and V values of the two forms of the enzyme. On the other hand, when a tryptic phosphodecapeptide derived from phosphorylated H2B histone was used as substrate, these effectors were always inhibitory apparently non-competitively with respect to the substrate. Using phosphorylated H1 histone as substrate, these effectors stimulated the large form of the enzyme 2-fold but inhibited the small form. With phosphorylase a as substrate, the reactions were also inhibited by these effectors irrespective of the enzyme employed. With respect to phosphorylase a, this inhibition was apparently of a competitive type for the large form and a non-competitive type for the small form of the enzyme.", "contents": "Effects of polyamine hydrochlorides and salts on phosphoprotein phosphatase. Polyamine hydrochlorides, NaCl and magnesium acetate stimulated the enzymatic dephosphorylation of phosphorylated H2B histone by two forms (large form, mol. wt. 250 000; small form, mol. wt. 30 000) of a pig heart phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16). These ionic compounds stimulated the large form of the enzyme 5--9-fold but stimulated the small form of theenzyme only 2-fold. With phosphorylated H2B histone as substrate, these effectors caused an increase in both Km and V values of the two forms of the enzyme. On the other hand, when a tryptic phosphodecapeptide derived from phosphorylated H2B histone was used as substrate, these effectors were always inhibitory apparently non-competitively with respect to the substrate. Using phosphorylated H1 histone as substrate, these effectors stimulated the large form of the enzyme 2-fold but inhibited the small form. With phosphorylase a as substrate, the reactions were also inhibited by these effectors irrespective of the enzyme employed. With respect to phosphorylase a, this inhibition was apparently of a competitive type for the large form and a non-competitive type for the small form of the enzyme."}
{"id": "PMID:210825", "title": "Nucleolar phosphoprotein phosphatase from Novikoff hepatoma and rat liver: characterization and partial purification.", "content": "Phosphoprotein phosphatase which dephosphorylates 32P-labeled nucleolar protein substrates was found in nucleoli of Novikoff hepatoma ascites cells and normal rat liver. The activity was extracted in high yield from nucleoli with 0.01 M Bis/Tris (pH 7.0). Low ionic strength was also required for activity: the activity was only 50% of maximum in 0.075 M NaCl. Activity was affected differently by various divalent cations: MgCl2 had little effect: CaCl2, MnCl2 and CoCl2 above 4 mM inhibited the activity 30--60%; ZnCl2 above 2 mM completely destroyed the activity. EDTA had no effect, indicating that divalent cations are probably not required. The enzyme activity was enhanced 20% by 5--8 mM dithiothreitol and was inhibited 60% by 7--10 mM N-ethylmaleimide indicating a requirement for free sulfhydryl groups. The Km of the extracted enzyme for 32P-labeled nucleolar protein was 0.6 mg/ml. The phosphatase was capable of dephosporylating the major phosphorylated nucleolar proteins C23-24 and B23-24 and also histone H1. The enzyme was purified more than 200-fold on hydroxyapatite followed by DEAE-Sephadex, which resolved the activity into three major components. The activity of enzyme extracted from Novikoff hepatoma nucleoli was approximately 2.5 times greater than from normal liver nucleoli.", "contents": "Nucleolar phosphoprotein phosphatase from Novikoff hepatoma and rat liver: characterization and partial purification. Phosphoprotein phosphatase which dephosphorylates 32P-labeled nucleolar protein substrates was found in nucleoli of Novikoff hepatoma ascites cells and normal rat liver. The activity was extracted in high yield from nucleoli with 0.01 M Bis/Tris (pH 7.0). Low ionic strength was also required for activity: the activity was only 50% of maximum in 0.075 M NaCl. Activity was affected differently by various divalent cations: MgCl2 had little effect: CaCl2, MnCl2 and CoCl2 above 4 mM inhibited the activity 30--60%; ZnCl2 above 2 mM completely destroyed the activity. EDTA had no effect, indicating that divalent cations are probably not required. The enzyme activity was enhanced 20% by 5--8 mM dithiothreitol and was inhibited 60% by 7--10 mM N-ethylmaleimide indicating a requirement for free sulfhydryl groups. The Km of the extracted enzyme for 32P-labeled nucleolar protein was 0.6 mg/ml. The phosphatase was capable of dephosporylating the major phosphorylated nucleolar proteins C23-24 and B23-24 and also histone H1. The enzyme was purified more than 200-fold on hydroxyapatite followed by DEAE-Sephadex, which resolved the activity into three major components. The activity of enzyme extracted from Novikoff hepatoma nucleoli was approximately 2.5 times greater than from normal liver nucleoli."}
{"id": "PMID:210826", "title": "Protein activator of cyclic AMP phosphodiesterase and cyclic nucleotide phosphodiesterase in bovine retina and bovine lens. Activity, subcellular distribution and kinetic parameters.", "content": "We have examined the activity of cyclic AMP phosphodiesterase, cyclic GMP phosphodiesterase and the protein activator of cyclic AMP phosphodiesterase in various anatomic and subcellular fractions of the bovine eye. Cyclic GMP hydrolysis was 1.6--12 times faster than hydrolysis of cyclic AMP in the subcellular fractions of the retina and in the precipitate of the rod outer segment. An opposite pattern was seen in the bovine lens, where the hyrolysis of cyclic AMP occurred 17 and 169 times faster than that of cyclic GMP in the supernatant and precipitate of lens, respectively. The activity of cyclic AMP phosphodiesterase was not affected by  ethylene-glycol bis(beta-aminoethylether)-N,N'-tetraacetic acid in any fractions except in the retinal supernatant, suggesting that the phosphodiesterase exists primarily as a Ca2+-independent, activator-independent form. However, the protein activator of cyclic AMP phosphodiesterase existed in all fractions examine. A complex kinetic patternwas observed for both cyclic AMP and cyllic GMP hydrolysis by the 105000 times g lens supernatant. The Michaelis constants for both cyclic AMP (1.3-10(-6) and 9.I-10(-6) M) and cyclic GMP (1.04-10(6) AND 1.22 10(-5) M) appeared to be similar.", "contents": "Protein activator of cyclic AMP phosphodiesterase and cyclic nucleotide phosphodiesterase in bovine retina and bovine lens. Activity, subcellular distribution and kinetic parameters. We have examined the activity of cyclic AMP phosphodiesterase, cyclic GMP phosphodiesterase and the protein activator of cyclic AMP phosphodiesterase in various anatomic and subcellular fractions of the bovine eye. Cyclic GMP hydrolysis was 1.6--12 times faster than hydrolysis of cyclic AMP in the subcellular fractions of the retina and in the precipitate of the rod outer segment. An opposite pattern was seen in the bovine lens, where the hyrolysis of cyclic AMP occurred 17 and 169 times faster than that of cyclic GMP in the supernatant and precipitate of lens, respectively. The activity of cyclic AMP phosphodiesterase was not affected by  ethylene-glycol bis(beta-aminoethylether)-N,N'-tetraacetic acid in any fractions except in the retinal supernatant, suggesting that the phosphodiesterase exists primarily as a Ca2+-independent, activator-independent form. However, the protein activator of cyclic AMP phosphodiesterase existed in all fractions examine. A complex kinetic patternwas observed for both cyclic AMP and cyllic GMP hydrolysis by the 105000 times g lens supernatant. The Michaelis constants for both cyclic AMP (1.3-10(-6) and 9.I-10(-6) M) and cyclic GMP (1.04-10(6) AND 1.22 10(-5) M) appeared to be similar."}
{"id": "PMID:210827", "title": "Surface binding and catabolism of low-density lipoprotein by circulating lymphocytes from patients with abetalipoproteinaemia, with observations on sterol synthesis in lymphocytes from one patient.", "content": "Surface binding of low-density lipoprotein (LDL), degradation of LDL protein and sterol synthesis were investigated in freshly isolated lymphocytes from normal and abetalipoproteinamic human subjects. LDL binding as a function of LDL concentration showed no evidence of the presence of high-affinity binding sites in fresh lymphocytes from either group of subjects. The rate of degradation of LDL protein by lymphocytes from the patients was no greater than that from the normal subjects and, in the fresh lymphocytes of the one patient studied, sterol synthesis was not increased. We conclude that the formation of LDL receptors and the synthesis of sterol in circulating lymphocytes are largely suppressed and that in normal subjects this may be due to the presence of some plasma constituent other than LDL, possibly the apoE protein. This conclusion is discussed in relation to the possible contribution of LDL receptors to the degradation of LDL protein in vivo.", "contents": "Surface binding and catabolism of low-density lipoprotein by circulating lymphocytes from patients with abetalipoproteinaemia, with observations on sterol synthesis in lymphocytes from one patient. Surface binding of low-density lipoprotein (LDL), degradation of LDL protein and sterol synthesis were investigated in freshly isolated lymphocytes from normal and abetalipoproteinamic human subjects. LDL binding as a function of LDL concentration showed no evidence of the presence of high-affinity binding sites in fresh lymphocytes from either group of subjects. The rate of degradation of LDL protein by lymphocytes from the patients was no greater than that from the normal subjects and, in the fresh lymphocytes of the one patient studied, sterol synthesis was not increased. We conclude that the formation of LDL receptors and the synthesis of sterol in circulating lymphocytes are largely suppressed and that in normal subjects this may be due to the presence of some plasma constituent other than LDL, possibly the apoE protein. This conclusion is discussed in relation to the possible contribution of LDL receptors to the degradation of LDL protein in vivo."}
{"id": "PMID:210828", "title": "High density lipoprotein metabolism in normolipidemic and cholesterol-fed rabbits.", "content": "New Zealand white rabbits were used to determine the compositional and metabolic changes induced in high density lipoproteins (HDL, rho = 1.063--1.21 g/ml) in response to cholesterol feeding. There was no change in total HDL cholesterol in plasma due to cholesterol feeding (12 weeks), but the triglyceride level was decreased to 29% of pretreatment values. Total protein content of HDL was decreased in response to cholesterol feeding, resulting in a significant increase in the cholesterol/protein ratio. There was a decrease in some isomer of the major apolipoproteins (A-I2) of HDL. The decay of radioactivity in HDL or its apolipoproteins was biphasic in both normolipidemic and hypercholesterolemic rabbits. The first phase was much more rapid than the second. The decay rates for the radioactivity in HDL depended upon the dietary status of the recipient animal.", "contents": "High density lipoprotein metabolism in normolipidemic and cholesterol-fed rabbits. New Zealand white rabbits were used to determine the compositional and metabolic changes induced in high density lipoproteins (HDL, rho = 1.063--1.21 g/ml) in response to cholesterol feeding. There was no change in total HDL cholesterol in plasma due to cholesterol feeding (12 weeks), but the triglyceride level was decreased to 29% of pretreatment values. Total protein content of HDL was decreased in response to cholesterol feeding, resulting in a significant increase in the cholesterol/protein ratio. There was a decrease in some isomer of the major apolipoproteins (A-I2) of HDL. The decay of radioactivity in HDL or its apolipoproteins was biphasic in both normolipidemic and hypercholesterolemic rabbits. The first phase was much more rapid than the second. The decay rates for the radioactivity in HDL depended upon the dietary status of the recipient animal."}
{"id": "PMID:210829", "title": "Effects of cytochalasin B on low-density lipoproteins metabolism by cultured human fibroblasts.", "content": "The role of cytoplasmic microfilaments in the metabolism of low-density lipoprotein by human fibroblasts was studied with the aid of cytochalasin B. At concentrations of 5--40 nmol/ml cytochalasin increased the surface binding but decreased the endocytosis of 125I-labelled low-density lipoprotein. Subsequent studies indicated that these changes reflected a reduction of the rate of internalisation of low-density lipoprotein receptors. Independent inhibitory effects were also observed on low-density lipoprotein degradation and on the cellular release of the trichloroacetic acid-soluble degradation products.", "contents": "Effects of cytochalasin B on low-density lipoproteins metabolism by cultured human fibroblasts. The role of cytoplasmic microfilaments in the metabolism of low-density lipoprotein by human fibroblasts was studied with the aid of cytochalasin B. At concentrations of 5--40 nmol/ml cytochalasin increased the surface binding but decreased the endocytosis of 125I-labelled low-density lipoprotein. Subsequent studies indicated that these changes reflected a reduction of the rate of internalisation of low-density lipoprotein receptors. Independent inhibitory effects were also observed on low-density lipoprotein degradation and on the cellular release of the trichloroacetic acid-soluble degradation products."}
{"id": "PMID:210830", "title": "Polyisoprenoid amphiphilic compounds as inhibitors of squalene synthesis and other microsomal enzymes.", "content": "Analogues of farnesyl pyrophosphate containing a farnesyl moiety and a variety of amine residues replacing the pyrophosphate have been synthesized. Most of these compounds were effective inhibitors of the synthesis of squalene and presqualene pyrophosphate from farnesyl pyrophosphate. 50% inhibition was obtained at concentrations between 50 and 100 micron. These analogues also inhibited other microsomal enzymes so they apparently function as general inhibitors of microsomal enzymes.", "contents": "Polyisoprenoid amphiphilic compounds as inhibitors of squalene synthesis and other microsomal enzymes. Analogues of farnesyl pyrophosphate containing a farnesyl moiety and a variety of amine residues replacing the pyrophosphate have been synthesized. Most of these compounds were effective inhibitors of the synthesis of squalene and presqualene pyrophosphate from farnesyl pyrophosphate. 50% inhibition was obtained at concentrations between 50 and 100 micron. These analogues also inhibited other microsomal enzymes so they apparently function as general inhibitors of microsomal enzymes."}
{"id": "PMID:210831", "title": "Phospholipid changes in synaptic membranes by lipolytic enzymes and subsequent restoration of opiate binding with phosphatidylserine.", "content": "A study has been made of the role of phosphatidylserine in stereospecific opiate binding to neural membranes, utilizing specific lipolytic enzymes to attack the lipid. At very low concentrations phospholipase A2 from bee venom will preferentially hydrolyze C22:6-fatty acid; and even after a few percent of the total phosphatidylserine is hydrolyzed, opiate binding is greatly inhibited. The addition of brain phosphatidylserine will restore opiate binding; however, when the inhibition approaches 50% restoration is only partial. Exposure of membranes to phosphatidylserine decarboxylase will partially inhibit opiate binding; and the binding returns to the control level after the addition of phosphatidylserine. The partial inhibition of opiate binding by low concentrations of Triton X-100, which presumably remove lipids, can be partially reversed by phosphatidylserine. The binding of 3H-naloxone, an opiate antagonist, is similar to agonists in its behavior towards phospholipases and phosphatidylserine; however, binding of naltrexone, also an antagonist, is far less responsive. It is concluded that the phosphatidylserine associated with the opiate receptor is the C18:0, 22:6-diacyl form, which is closely associated with protein.", "contents": "Phospholipid changes in synaptic membranes by lipolytic enzymes and subsequent restoration of opiate binding with phosphatidylserine. A study has been made of the role of phosphatidylserine in stereospecific opiate binding to neural membranes, utilizing specific lipolytic enzymes to attack the lipid. At very low concentrations phospholipase A2 from bee venom will preferentially hydrolyze C22:6-fatty acid; and even after a few percent of the total phosphatidylserine is hydrolyzed, opiate binding is greatly inhibited. The addition of brain phosphatidylserine will restore opiate binding; however, when the inhibition approaches 50% restoration is only partial. Exposure of membranes to phosphatidylserine decarboxylase will partially inhibit opiate binding; and the binding returns to the control level after the addition of phosphatidylserine. The partial inhibition of opiate binding by low concentrations of Triton X-100, which presumably remove lipids, can be partially reversed by phosphatidylserine. The binding of 3H-naloxone, an opiate antagonist, is similar to agonists in its behavior towards phospholipases and phosphatidylserine; however, binding of naltrexone, also an antagonist, is far less responsive. It is concluded that the phosphatidylserine associated with the opiate receptor is the C18:0, 22:6-diacyl form, which is closely associated with protein."}
{"id": "PMID:210832", "title": "Triglyceridase and phospholipase A1 activities of rat-heart lipoprotein lipase. Influence of apolipoproteins C-II and C-III.", "content": "The influence of purified human apolipoprotein C-II on phospholipase A1 and triglyceridase activities of lipoprotein lipase were compared. Lipoprotein lipase was obtained from rat hearts by perfusion with a medium containing heparin and purified on a heparin Sepharose 4-B column. Using phosphatidyl-ethanolamine-coated triglyceride particles as substrate it was found that the phospholipase A1 and triglyceridase activities of lipoprotein lipase similarly depend on the presence of apolipoprotein C-II. Apolipoprotein C-III cannot replace apolipoprotein C-II. However, addition of apolipoprotein C-III in the presence of C-II affects both lipase activities. While strong inhibition of triglyceridase activity was observed under these conditions, phospholipase A1 activity was slightly stimulated. On the basis of these findings a model was constructed for the role of apolipoprotein C-II in lipoprotein lipase action.", "contents": "Triglyceridase and phospholipase A1 activities of rat-heart lipoprotein lipase. Influence of apolipoproteins C-II and C-III. The influence of purified human apolipoprotein C-II on phospholipase A1 and triglyceridase activities of lipoprotein lipase were compared. Lipoprotein lipase was obtained from rat hearts by perfusion with a medium containing heparin and purified on a heparin Sepharose 4-B column. Using phosphatidyl-ethanolamine-coated triglyceride particles as substrate it was found that the phospholipase A1 and triglyceridase activities of lipoprotein lipase similarly depend on the presence of apolipoprotein C-II. Apolipoprotein C-III cannot replace apolipoprotein C-II. However, addition of apolipoprotein C-III in the presence of C-II affects both lipase activities. While strong inhibition of triglyceridase activity was observed under these conditions, phospholipase A1 activity was slightly stimulated. On the basis of these findings a model was constructed for the role of apolipoprotein C-II in lipoprotein lipase action."}
{"id": "PMID:210833", "title": "Effect of immunoglobulin G on membrane-bound enzyme activity of sarcoma 180 cells.", "content": "Changes in the activity of membrane bound ATPase of Sarcoma 180 cells caused by immunoglobulin G (IgG) of anti-Sarcoma 180 was investigated in relation to the incorporation of amino acid by the cells. Enzymatic activity of ATPase was increased up to 160% of the original activity upon incubation of the cell with IgG. Kinetic studies showed that IgG did not change the affinity of this enzyme for the substrate, but exerted influence upon catalytic efficiency of the enzyme. The rate of incorporation of leucine into Sarcoma 180 cells was also affected by IgG, as observed in the effect of IgG on the enzymatic reaction of the cells.", "contents": "Effect of immunoglobulin G on membrane-bound enzyme activity of sarcoma 180 cells. Changes in the activity of membrane bound ATPase of Sarcoma 180 cells caused by immunoglobulin G (IgG) of anti-Sarcoma 180 was investigated in relation to the incorporation of amino acid by the cells. Enzymatic activity of ATPase was increased up to 160% of the original activity upon incubation of the cell with IgG. Kinetic studies showed that IgG did not change the affinity of this enzyme for the substrate, but exerted influence upon catalytic efficiency of the enzyme. The rate of incorporation of leucine into Sarcoma 180 cells was also affected by IgG, as observed in the effect of IgG on the enzymatic reaction of the cells."}
{"id": "PMID:210834", "title": "Lack of altered cyclic nucleotide phosphodiesterase activity in the aorta and heart of the spontaneously hypertensive rat.", "content": "DEAE-cellulose chromatography demonstrated that the levels of the individual cyclic nucleotide phosphodiesterases were unchanged in the aorta and heart of the spontaneously hypertensive rat as compared with the normotensive control rat. Three peaks of cyclic nucleotide phosphodiesterases activity were observed in both heart and aorta. Peak I enzyme hybrolyzed predominantly cyclic GMP while peak III enzyme hydrolyzed predominantly cyclic AMP. Peak II enzyme was less specific but hydrolyzed more cyclic GMP than cyclic AMP. The levels of phosphodiesterase activator in aorta and the responsiveness of peaks I and II from aorta and heart to activator were unchanged in the hypertensive rat. Therefore the decrease in cyclic AMP levels observed by others in aorta and heart of the spontaneously hypertensive rat were probably not due to altered phosphodiesterase activity.", "contents": "Lack of altered cyclic nucleotide phosphodiesterase activity in the aorta and heart of the spontaneously hypertensive rat. DEAE-cellulose chromatography demonstrated that the levels of the individual cyclic nucleotide phosphodiesterases were unchanged in the aorta and heart of the spontaneously hypertensive rat as compared with the normotensive control rat. Three peaks of cyclic nucleotide phosphodiesterases activity were observed in both heart and aorta. Peak I enzyme hybrolyzed predominantly cyclic GMP while peak III enzyme hydrolyzed predominantly cyclic AMP. Peak II enzyme was less specific but hydrolyzed more cyclic GMP than cyclic AMP. The levels of phosphodiesterase activator in aorta and the responsiveness of peaks I and II from aorta and heart to activator were unchanged in the hypertensive rat. Therefore the decrease in cyclic AMP levels observed by others in aorta and heart of the spontaneously hypertensive rat were probably not due to altered phosphodiesterase activity."}
{"id": "PMID:210835", "title": "Dissociation of beta-adrenergic receptors from hormone responsiveness during maturation of the rat reticulocyte.", "content": "Intact rat erythrocytes and reticulocytes have been studied in relation to their concentration of beta-adrenergic receptors and their responsiveness to beta-adrenergic catecholamines. Characteristics of the beta-receptor, as determined by binding of 125I-labelled hydroxybenzylpindolol, were compared among control erythrocytes and reticulocytes. The dissociation constant (Kd = 0.1--0.2 nM), association and dissociation kinetics, and stereospecificity for (--)-isomers of agonists and antagonists were similar in both cell types. The reticulocyte population contained four times more receptors per cell than the control erythrocytes. However, reticulocytes were 25 times more responsive than control cells to isoproterenol, as measured by the formation of cyclic AMP. After peak reticulocytosis, cells rapidly lost 95% of their maximum hormone responsiveness, but beta-receptors declined much more slowly. The 4-fold decrease in beta-receptors was associated with a 4-fold decrease in cell volume as the reticulocytes matured. The density of beta-receptors was unchanged. However, responsiveness to isoproterenol in the reticulocytes when expressed on the basis of cell volume was still nine times greater than the control cells. Thus, maturation of reticulocytes is associated with an uncoupling of persistent beta-receptors from catecholamine responsiveness.", "contents": "Dissociation of beta-adrenergic receptors from hormone responsiveness during maturation of the rat reticulocyte. Intact rat erythrocytes and reticulocytes have been studied in relation to their concentration of beta-adrenergic receptors and their responsiveness to beta-adrenergic catecholamines. Characteristics of the beta-receptor, as determined by binding of 125I-labelled hydroxybenzylpindolol, were compared among control erythrocytes and reticulocytes. The dissociation constant (Kd = 0.1--0.2 nM), association and dissociation kinetics, and stereospecificity for (--)-isomers of agonists and antagonists were similar in both cell types. The reticulocyte population contained four times more receptors per cell than the control erythrocytes. However, reticulocytes were 25 times more responsive than control cells to isoproterenol, as measured by the formation of cyclic AMP. After peak reticulocytosis, cells rapidly lost 95% of their maximum hormone responsiveness, but beta-receptors declined much more slowly. The 4-fold decrease in beta-receptors was associated with a 4-fold decrease in cell volume as the reticulocytes matured. The density of beta-receptors was unchanged. However, responsiveness to isoproterenol in the reticulocytes when expressed on the basis of cell volume was still nine times greater than the control cells. Thus, maturation of reticulocytes is associated with an uncoupling of persistent beta-receptors from catecholamine responsiveness."}
{"id": "PMID:210836", "title": "Influence of calcium on phosphorylation of a synaptosomal protein.", "content": "Synaptosomal proteins isolated from rat cerebral cortex were phosphorylated endogeneously in the presence of [gamma-32P]ATP. The phosphorylated proteins were found to be membrane bound by differential and density gradient centrifugation. In contrast to the phosphorylation of all synaptosomal proteins, phosphorylation of one protein (C), 41 000--43 000 daltons, was inhibited by Mg2+ and stimulated by Ca2+. In addition, the ionophores X537A and A23187, as well as papaverine, selectively enhanced phosphorylation of protein C without affecting phosphorylation of the outer proteins. Cyclic AMP did not influence the phosphorylation of protein C but markedly affected the phosphorylation of other synaptosomal proteins. It appears that the phosphorylation of protein C is stimulated by agents which trigger the release of neurotransmitters (Ca2+, X537A, A23187 and papaverine), and is inhibited by Mg2+, which inhibits release. It is proposed that the phosphorylation of protein C is related to membranal events underlying the release of neurotransmitters.", "contents": "Influence of calcium on phosphorylation of a synaptosomal protein. Synaptosomal proteins isolated from rat cerebral cortex were phosphorylated endogeneously in the presence of [gamma-32P]ATP. The phosphorylated proteins were found to be membrane bound by differential and density gradient centrifugation. In contrast to the phosphorylation of all synaptosomal proteins, phosphorylation of one protein (C), 41 000--43 000 daltons, was inhibited by Mg2+ and stimulated by Ca2+. In addition, the ionophores X537A and A23187, as well as papaverine, selectively enhanced phosphorylation of protein C without affecting phosphorylation of the outer proteins. Cyclic AMP did not influence the phosphorylation of protein C but markedly affected the phosphorylation of other synaptosomal proteins. It appears that the phosphorylation of protein C is stimulated by agents which trigger the release of neurotransmitters (Ca2+, X537A, A23187 and papaverine), and is inhibited by Mg2+, which inhibits release. It is proposed that the phosphorylation of protein C is related to membranal events underlying the release of neurotransmitters."}
{"id": "PMID:210837", "title": "Disintegration of phosphatidylcholine liposomes in plasma as a result of interaction with high-density lipoproteins.", "content": "1. During in vitro incubation of liposomes or unilamellar vesicles prepared from egg-yolk or rat-liver phosphatidylcholine with human, monkey or rat plasma the phospholipid becomes associated with a high molecular weight protein-containing component. 2. The phosphatidylcholine . protein complex thus formed co-chromatographs with high-density lipoprotein on Ultrogel AcA34 and has the same immunoelectrophoretic properties as this lipoprotein. 3. Release of the phosphatidylcholine from liposomes was also observed when liposomes were incubated with pure monkey high-density lipoproteins. Under those conditions some transfer of protein from the lipoprotein to the liposomes was observed as well. 4. The observed release of phospholipid from the liposomes is a one-way process, as the specific radioactivity of liposome-associated phosphatidylcholine remained constant during incubation with plasma. 5. It is concluded that either the lipoprotein particle takes up additional phospholipid or that a new complex is formed from protein constituents of the lipoprotein and the liposomal phosphatidylcholine. 6. Massive release of entrapped 125I-labeled albumin from the liposome during incubation with plasma suggests that the observed release of phosphatidylcholine from the liposomes has a highly destructive influence on the liposomal structure. 7. Our results are discussed with special reference to the use of liposomes as intravenous carriers of drugs and enzymes.", "contents": "Disintegration of phosphatidylcholine liposomes in plasma as a result of interaction with high-density lipoproteins. 1. During in vitro incubation of liposomes or unilamellar vesicles prepared from egg-yolk or rat-liver phosphatidylcholine with human, monkey or rat plasma the phospholipid becomes associated with a high molecular weight protein-containing component. 2. The phosphatidylcholine . protein complex thus formed co-chromatographs with high-density lipoprotein on Ultrogel AcA34 and has the same immunoelectrophoretic properties as this lipoprotein. 3. Release of the phosphatidylcholine from liposomes was also observed when liposomes were incubated with pure monkey high-density lipoproteins. Under those conditions some transfer of protein from the lipoprotein to the liposomes was observed as well. 4. The observed release of phospholipid from the liposomes is a one-way process, as the specific radioactivity of liposome-associated phosphatidylcholine remained constant during incubation with plasma. 5. It is concluded that either the lipoprotein particle takes up additional phospholipid or that a new complex is formed from protein constituents of the lipoprotein and the liposomal phosphatidylcholine. 6. Massive release of entrapped 125I-labeled albumin from the liposome during incubation with plasma suggests that the observed release of phosphatidylcholine from the liposomes has a highly destructive influence on the liposomal structure. 7. Our results are discussed with special reference to the use of liposomes as intravenous carriers of drugs and enzymes."}
{"id": "PMID:210838", "title": "Mechanisms of corticotropin action in rat adrenal cells. I. The effects of inhibitors of protein synthesis and of microfilament formation on corticosterone synthesis.", "content": "The contributions of protein synthesis and formation of microtubules and microfilaments to corticotropin-stimulated steroidogenesis in rat adrenal cell suspensions has been assessed by use of a series of inhibitors to each function. Five inhibitors of protein synthesis (cycloheximide, puromycin, blastocidin S, anisomycin, and trichodermin) each exhibited time-dependent inhibition of corticotropin-stimulated steroidogenesis. For the first 30 min, steroidogenesis was more extensively inhibited than protein synthesis, after which the effectiveness of the inhibitors diminished on steroidogenesis but not on protein synthesis. The reversal effect was not observed at high levels of inhibitors. One inhibitor of microfilament formation (cytochalasin B) and four inhibitors of microtubule formation (colchicine, podophyllotoxin, vinblastine sulfate and griseofulvin) inhibited steroidogenesis without inhibiting protein synthesis and without any reversal effect with prolonged incubation. The actions of all ten inhibitors were shown to be fully reversible. Cell superfusion of adrenal cells showed that the decay of steroidogenesis upon addition of all the protein synthesis inhibitors was similar to decay upon removal of corticotropin from the medium (t1/2 = 4--6 min). Recoveries from inhibition upon removal of the inhibitors were similar to each other and comparable to initial corticotropin stimulation of the cells (lag of 3--5 min, t1/2=7--9 min). Similar kinetics of inhibition and recovery were observed for vinblastine sulfate while a direct inhibition of cytochrome P-450scc by aminoglutethimide was complete within 1 min and was rapidly reversed. Injection of each inhibitor (all classes) into hypophysectomized rats inhibited the elevation of plasma corticosterone by corticotropin. The extent of cholesterol combination with cytochrome P-450scc in adrenal mitochondria isolated from these rats was also decreased by all of the inhibitors. Decreases in plasma corticosterone correlated directly with decreases in cholesterol combination with cytochrome P-450scc (r=0.94). It is concluded that protein synthesis and steroidogenesis must be intimately coupled probably due to the requirement of a labile protein for cholesterol transport to cytochrome P-450scc. An involvement of microtubules and microfilaments in this process is clearly indicated.", "contents": "Mechanisms of corticotropin action in rat adrenal cells. I. The effects of inhibitors of protein synthesis and of microfilament formation on corticosterone synthesis. The contributions of protein synthesis and formation of microtubules and microfilaments to corticotropin-stimulated steroidogenesis in rat adrenal cell suspensions has been assessed by use of a series of inhibitors to each function. Five inhibitors of protein synthesis (cycloheximide, puromycin, blastocidin S, anisomycin, and trichodermin) each exhibited time-dependent inhibition of corticotropin-stimulated steroidogenesis. For the first 30 min, steroidogenesis was more extensively inhibited than protein synthesis, after which the effectiveness of the inhibitors diminished on steroidogenesis but not on protein synthesis. The reversal effect was not observed at high levels of inhibitors. One inhibitor of microfilament formation (cytochalasin B) and four inhibitors of microtubule formation (colchicine, podophyllotoxin, vinblastine sulfate and griseofulvin) inhibited steroidogenesis without inhibiting protein synthesis and without any reversal effect with prolonged incubation. The actions of all ten inhibitors were shown to be fully reversible. Cell superfusion of adrenal cells showed that the decay of steroidogenesis upon addition of all the protein synthesis inhibitors was similar to decay upon removal of corticotropin from the medium (t1/2 = 4--6 min). Recoveries from inhibition upon removal of the inhibitors were similar to each other and comparable to initial corticotropin stimulation of the cells (lag of 3--5 min, t1/2=7--9 min). Similar kinetics of inhibition and recovery were observed for vinblastine sulfate while a direct inhibition of cytochrome P-450scc by aminoglutethimide was complete within 1 min and was rapidly reversed. Injection of each inhibitor (all classes) into hypophysectomized rats inhibited the elevation of plasma corticosterone by corticotropin. The extent of cholesterol combination with cytochrome P-450scc in adrenal mitochondria isolated from these rats was also decreased by all of the inhibitors. Decreases in plasma corticosterone correlated directly with decreases in cholesterol combination with cytochrome P-450scc (r=0.94). It is concluded that protein synthesis and steroidogenesis must be intimately coupled probably due to the requirement of a labile protein for cholesterol transport to cytochrome P-450scc. An involvement of microtubules and microfilaments in this process is clearly indicated."}
{"id": "PMID:210839", "title": "Inhibition of steroidogenic response to corticotropin in mouse adrenal tumor cells (Y-1) by the ionophore A23187. Role of protein biosynthesis.", "content": "Addition of the ionophore A23187 to Y-1 mouse adrenal tumor cells in monolayer culture inhibits steroidogenesis and the steroidogenic response to corticotropin (50% inhibition at 1 . 10(-7)M). Inhibition is rapid in onset and is not overcome by addition of external Ca2+. The ionophore also inhibits stimulation of steroid synthesis by cyclic AMP. A23187 inhibits incorporation of the amino acid lysine into protein by Y-1 cells and the dose dependence of this inhibition closely resembles that of the inhibition of the steroidogenic response to corticotropin. Addition of A23187 to a subcellular system for protein synthesis prepared from Y-1 cells, inhibits incorporation of the amino acid phenylalanine into protein and this effect is not overcome by high concentrations of Ca2+. The inhibitory effect of A23187 on the response to corticotropin, like that response itself, takes place at some part of steroid synthesis after entry of cholesterol into the cells and before the side-chain cleavage of cholesterol. These studies confirm the importance of protein synthesis in the response to corticotropin and demonstrate that the effect of protein synthesized under the influence of corticotropin is exerted at some point in the events which bring substrate (cholesterol) to the mitochondrial side-chain cleavage enzyme system. It is also shown that A23187 inhibits protein synthesis, and hence the response to corticotropin, by a mechanism which is independent of the concentration of available Ca2+.", "contents": "Inhibition of steroidogenic response to corticotropin in mouse adrenal tumor cells (Y-1) by the ionophore A23187. Role of protein biosynthesis. Addition of the ionophore A23187 to Y-1 mouse adrenal tumor cells in monolayer culture inhibits steroidogenesis and the steroidogenic response to corticotropin (50% inhibition at 1 . 10(-7)M). Inhibition is rapid in onset and is not overcome by addition of external Ca2+. The ionophore also inhibits stimulation of steroid synthesis by cyclic AMP. A23187 inhibits incorporation of the amino acid lysine into protein by Y-1 cells and the dose dependence of this inhibition closely resembles that of the inhibition of the steroidogenic response to corticotropin. Addition of A23187 to a subcellular system for protein synthesis prepared from Y-1 cells, inhibits incorporation of the amino acid phenylalanine into protein and this effect is not overcome by high concentrations of Ca2+. The inhibitory effect of A23187 on the response to corticotropin, like that response itself, takes place at some part of steroid synthesis after entry of cholesterol into the cells and before the side-chain cleavage of cholesterol. These studies confirm the importance of protein synthesis in the response to corticotropin and demonstrate that the effect of protein synthesized under the influence of corticotropin is exerted at some point in the events which bring substrate (cholesterol) to the mitochondrial side-chain cleavage enzyme system. It is also shown that A23187 inhibits protein synthesis, and hence the response to corticotropin, by a mechanism which is independent of the concentration of available Ca2+."}
{"id": "PMID:210840", "title": "Alterations in activities of cyclic nucleotide systems and in beta-adrenergic receptor-mediated activation of cyclic AMP-dependent protein kinase during progression and regression of isoproterenol-induced cardiac hypertrophy.", "content": "Initial and transient increases in the basal levels of cyclic GMP in the heart were noted prior to cardiac hypertrophy in rats administered isoproterenol. Increased levels of cyclic AMP-phosphodiesterase (in both the soluble and particulate fractions) and stimulatory modulator of cyclic GMP-dependent protein kinase, however, were associated with the progression, or the state, of cardiomegaly, with their levels returning to the control values upon regression of the hypertrophy. The levels of cyclic GMP phosphodiesterase in the soluble fraction were lower, whereas those in the particulate fraction were higher, in the hypertrophied heart than the control. In cardiac hypertrophy, the maximal activity ratio(--cyclic AMP/+cyclic AMP) of cyclic AMP-dependent protein kinase in the incubated minced heart caused by isoproterenol was lower, whereas the concentration of isoproterenol required to increase the activity ratio half-maximally was higher than controls; the reduced responsiveness to the drug, however, was reversed when the hypertrophy regressed. These observations, taken collectively, appear to suggest that the desensitization of the beta-adrenergic mechanism seen in the cardiac hypertrophy produced by repeated administration of isoproterenol is associated with adaptive modifications in certain parameters of the cyclic nucleotide systems.", "contents": "Alterations in activities of cyclic nucleotide systems and in beta-adrenergic receptor-mediated activation of cyclic AMP-dependent protein kinase during progression and regression of isoproterenol-induced cardiac hypertrophy. Initial and transient increases in the basal levels of cyclic GMP in the heart were noted prior to cardiac hypertrophy in rats administered isoproterenol. Increased levels of cyclic AMP-phosphodiesterase (in both the soluble and particulate fractions) and stimulatory modulator of cyclic GMP-dependent protein kinase, however, were associated with the progression, or the state, of cardiomegaly, with their levels returning to the control values upon regression of the hypertrophy. The levels of cyclic GMP phosphodiesterase in the soluble fraction were lower, whereas those in the particulate fraction were higher, in the hypertrophied heart than the control. In cardiac hypertrophy, the maximal activity ratio(--cyclic AMP/+cyclic AMP) of cyclic AMP-dependent protein kinase in the incubated minced heart caused by isoproterenol was lower, whereas the concentration of isoproterenol required to increase the activity ratio half-maximally was higher than controls; the reduced responsiveness to the drug, however, was reversed when the hypertrophy regressed. These observations, taken collectively, appear to suggest that the desensitization of the beta-adrenergic mechanism seen in the cardiac hypertrophy produced by repeated administration of isoproterenol is associated with adaptive modifications in certain parameters of the cyclic nucleotide systems."}
{"id": "PMID:210842", "title": "Chemically shifted singlet oxygen spectrum.", "content": "The estimated light emission spectrum was determined for a singlet oxygen (1O2)-producing system, NaOCl + H2O2, alone and in the presence of tryptophan and bovine serum albumin. Tryptophan and bovine serum albumin caused a decrease in the red emission of 1O2 and an increase in the amount of shorter wavelength light. This effect was due to chemiluminescence rather than fluorescence. Arachidonic acid caused a similar spectral shift, while guanosine demonstrated a late chemiluminescent reaction of predominantly short wavelength light in the presence of 1O2.", "contents": "Chemically shifted singlet oxygen spectrum. The estimated light emission spectrum was determined for a singlet oxygen (1O2)-producing system, NaOCl + H2O2, alone and in the presence of tryptophan and bovine serum albumin. Tryptophan and bovine serum albumin caused a decrease in the red emission of 1O2 and an increase in the amount of shorter wavelength light. This effect was due to chemiluminescence rather than fluorescence. Arachidonic acid caused a similar spectral shift, while guanosine demonstrated a late chemiluminescent reaction of predominantly short wavelength light in the presence of 1O2."}
{"id": "PMID:210843", "title": "The levels of cyclic GMP and glucose 1,6-diphosphate, and the activity of phosphofructokinase, in muscle from normal and dystrophic mice.", "content": "A striking reduction in the levels of glucose 1,6-diphosphate and an increase in cyclic GMP were found in muscle from dystrophic mice. Concomitant to these changes, the allosteric activity of phosphofructokinase was found to be markedly reduced. These findings could offer an explanation for the observed reduction in glycolysis in the dystrophic muscle.", "contents": "The levels of cyclic GMP and glucose 1,6-diphosphate, and the activity of phosphofructokinase, in muscle from normal and dystrophic mice. A striking reduction in the levels of glucose 1,6-diphosphate and an increase in cyclic GMP were found in muscle from dystrophic mice. Concomitant to these changes, the allosteric activity of phosphofructokinase was found to be markedly reduced. These findings could offer an explanation for the observed reduction in glycolysis in the dystrophic muscle."}
{"id": "PMID:210844", "title": "The interaction of arsenite with the molybdenum center of chicken liver xanthine dehydrogenase.", "content": "Inactivation of chicken liver xanthine dehydrogenase by arsenite is reflected in the molybdenum electron paramagnetic resonance signal at g = 1.97. The arsenite spectrum shows additional splittings and considerable broadening yet remains comparable to the native in total intensity. Further subtle alterations of the molybdenum signal of arsenite-treated enzyme are seen in the presence of purine-type substrates or inhibitors.", "contents": "The interaction of arsenite with the molybdenum center of chicken liver xanthine dehydrogenase. Inactivation of chicken liver xanthine dehydrogenase by arsenite is reflected in the molybdenum electron paramagnetic resonance signal at g = 1.97. The arsenite spectrum shows additional splittings and considerable broadening yet remains comparable to the native in total intensity. Further subtle alterations of the molybdenum signal of arsenite-treated enzyme are seen in the presence of purine-type substrates or inhibitors."}
{"id": "PMID:210845", "title": "Spectral and electron paramagnetic resonance investigations of copper (II) complexes linear-chain fatty diacids.", "content": "Electron paramagnetic resonance spectra of polycrystalline copper complexes of butanedioic, pentanedioic, hexanedioic, heptanedioic, and decanedioic acids are presented, together with 77 K electronic spectra. The complexes are formulated as dimeric copper carboxylate units linked into infinite chains. Monomer impurities are also present and increase in quantity with the length of the diacid. The monomer and dimer signals occur at very different field strengths, but the g values calculated from the S = 1/2 spectra are similar to those calculated from the S = 1 spectra. The EPR method can thus be used to locate copper ions in possible biological frameworks and to study the geometry around the metal sites. The distortion from axial symmetry around the copper increases with the length of the diacid, as shown by the observed zero-field splitting parameters. Gaussian analysis of the optical absorptions yields information used with EPR data to calculate covalency and Fermi contact terms. Sodium, potassium, and lithium salts transform the dimeric polymers into monomeric polymers. The presence of magnetic exchange interactions in copper dicarboxylates is discussed and thereby shown to be of interest in the study of copper ions in molecules of biological importance containing carboxylate groups.", "contents": "Spectral and electron paramagnetic resonance investigations of copper (II) complexes linear-chain fatty diacids. Electron paramagnetic resonance spectra of polycrystalline copper complexes of butanedioic, pentanedioic, hexanedioic, heptanedioic, and decanedioic acids are presented, together with 77 K electronic spectra. The complexes are formulated as dimeric copper carboxylate units linked into infinite chains. Monomer impurities are also present and increase in quantity with the length of the diacid. The monomer and dimer signals occur at very different field strengths, but the g values calculated from the S = 1/2 spectra are similar to those calculated from the S = 1 spectra. The EPR method can thus be used to locate copper ions in possible biological frameworks and to study the geometry around the metal sites. The distortion from axial symmetry around the copper increases with the length of the diacid, as shown by the observed zero-field splitting parameters. Gaussian analysis of the optical absorptions yields information used with EPR data to calculate covalency and Fermi contact terms. Sodium, potassium, and lithium salts transform the dimeric polymers into monomeric polymers. The presence of magnetic exchange interactions in copper dicarboxylates is discussed and thereby shown to be of interest in the study of copper ions in molecules of biological importance containing carboxylate groups."}
{"id": "PMID:210846", "title": "Complexes of sulfur-containing ligands. I. Factors influencing complex formation between D-penicillamine and copper (II) ion.", "content": "Complex formation and redox reactions between copper (II) ion and D-penicillamine were studied in detail as functions of the metal/-ligand ratio and the concentration of halide ions. It was established that a copper (I)- D-penicillamine polymeric complex of amphoteric character is formed when excess D-penicillamine is present. When the D-penicillamine/copper (II) ratio = 1.45 in the starting reaction mixture, a mixed valence complex with an intense red-violet color is formed. The formation of this compound, which contains 44% copper (II) ion, is greatly influenced by the experimental conditions, primarily by the concentration of halide ions. The main chemical and physical characteristics of the mixed valence complex were determined via magnetic and spectroscopic measurements. It was further established that a very intense blue complex is formed when the D-penicillamine/copper (II) ratio = 2 and halide ions are present. On the basis of the nature of the products formed under various conditions it was concluded that the copper (II)-D-penicillamine system may serve as a good model for studying the binding sites of copper-containing proteins.", "contents": "Complexes of sulfur-containing ligands. I. Factors influencing complex formation between D-penicillamine and copper (II) ion. Complex formation and redox reactions between copper (II) ion and D-penicillamine were studied in detail as functions of the metal/-ligand ratio and the concentration of halide ions. It was established that a copper (I)- D-penicillamine polymeric complex of amphoteric character is formed when excess D-penicillamine is present. When the D-penicillamine/copper (II) ratio = 1.45 in the starting reaction mixture, a mixed valence complex with an intense red-violet color is formed. The formation of this compound, which contains 44% copper (II) ion, is greatly influenced by the experimental conditions, primarily by the concentration of halide ions. The main chemical and physical characteristics of the mixed valence complex were determined via magnetic and spectroscopic measurements. It was further established that a very intense blue complex is formed when the D-penicillamine/copper (II) ratio = 2 and halide ions are present. On the basis of the nature of the products formed under various conditions it was concluded that the copper (II)-D-penicillamine system may serve as a good model for studying the binding sites of copper-containing proteins."}
{"id": "PMID:210847", "title": "Structural and exchange properties of \"Co(III)-phenanthroline-ATP\": a labeling reagent for the active site of ATPases.", "content": "This paper reports on 1H and 31P NMR as well as EPR measurements of the labeling reagent of ATPase sites, \"Co(III)-(phen)-ATP.\" This complex is found to be paramagnetic, as deduced both from its EPR spectrum and from the significant broadening, though almost unshifted, proton and phosphorus resonances. This paramagnetism is a result of the incorporation of the superoxide free-radical anion in the coordination sphere of the trivalent cobalt ion. Evidence for the presence of superoxide in the complex is based on competition experiments with cyanide, which is able to displace the superoxide anion. The latter was identified by its inducing effect on the photoreactivity of luminol. The displacement of superoxide by cyanide was accompanied by the abolition of the paramagnetism of the complex. The relative distances between the protons and phosphorus atoms of ATP and the superoxide anion in the complex were calculated using the NMR line-broadening data. Structural models compatible with the experimental results are proposed. Under conditions of excess of adenine nucleotides or phenanthroline, the coordinated ATP molecule becomes exchangeable. This phenomenon is attributed to the labilization of the cobaltic ion ligands induced by the superoxide anion.", "contents": "Structural and exchange properties of \"Co(III)-phenanthroline-ATP\": a labeling reagent for the active site of ATPases. This paper reports on 1H and 31P NMR as well as EPR measurements of the labeling reagent of ATPase sites, \"Co(III)-(phen)-ATP.\" This complex is found to be paramagnetic, as deduced both from its EPR spectrum and from the significant broadening, though almost unshifted, proton and phosphorus resonances. This paramagnetism is a result of the incorporation of the superoxide free-radical anion in the coordination sphere of the trivalent cobalt ion. Evidence for the presence of superoxide in the complex is based on competition experiments with cyanide, which is able to displace the superoxide anion. The latter was identified by its inducing effect on the photoreactivity of luminol. The displacement of superoxide by cyanide was accompanied by the abolition of the paramagnetism of the complex. The relative distances between the protons and phosphorus atoms of ATP and the superoxide anion in the complex were calculated using the NMR line-broadening data. Structural models compatible with the experimental results are proposed. Under conditions of excess of adenine nucleotides or phenanthroline, the coordinated ATP molecule becomes exchangeable. This phenomenon is attributed to the labilization of the cobaltic ion ligands induced by the superoxide anion."}
{"id": "PMID:210849", "title": "Neonatal parathyroid secretion and renal receptor maturation in premature infants.", "content": "16 premature infants with normal trophicity were studied during the 1st week of life using serum parathormone (IPTH) dosage and evaluation of renal tubule maturation by the effect of exogenous parathormone (PTE) on urinary elimination of 3':5'-cyclic adenosine monophosphate (cAMP). As of the 1st day, IPTH levels reached or surpassed those in the adult. Prematurity thus does not appear to influence parathormone response. Given the specificity of the dosage antiserum, it appears reasonable that the PTH detected is biologically active. After PTE, urinary elimination of cAMP does not appreciably increase until the 6th day, while still remaining much lower than adult levels. The lower the weight of the premature infant, the less intense the response of the kidney. It thus seems possible that the later development of renal parathormone receptor in the premature infant may be a factor responsible for neonatal hypocalcemia with hyperphosphatemia.", "contents": "Neonatal parathyroid secretion and renal receptor maturation in premature infants. 16 premature infants with normal trophicity were studied during the 1st week of life using serum parathormone (IPTH) dosage and evaluation of renal tubule maturation by the effect of exogenous parathormone (PTE) on urinary elimination of 3':5'-cyclic adenosine monophosphate (cAMP). As of the 1st day, IPTH levels reached or surpassed those in the adult. Prematurity thus does not appear to influence parathormone response. Given the specificity of the dosage antiserum, it appears reasonable that the PTH detected is biologically active. After PTE, urinary elimination of cAMP does not appreciably increase until the 6th day, while still remaining much lower than adult levels. The lower the weight of the premature infant, the less intense the response of the kidney. It thus seems possible that the later development of renal parathormone receptor in the premature infant may be a factor responsible for neonatal hypocalcemia with hyperphosphatemia."}
{"id": "PMID:210850", "title": "Influence of vincamine and piracetam on sleep--waking pattern of the cat.", "content": "The effect of Vincamine and Piracetam, two geriatric drugs, on sleep behavior of the laboratory cat was studied. The animals were chronically prepared for recording of the EEG of the cerebral cortex, the lateral geniculate body, and the hippocampus, and for recording of eye movements, the muscular tonus and respiration. During the experiment, sleep and waking behavior were monitored by the above mentioned telemetrically transmitted indicators and also through observation via closed-circuit television. Both Vincamine and Piracetam in doses of 1 and 300 mg/kg p.o., respectively, enhance absolute and relative amounts of paradoxical sleep (PS). Smaller doses have a lesser or no effect on PS. Larger doses again have little effect or else, in the first few hours after application, reduce PS and total amount of sleep. Both drugs have little effect on slow wave and total sleep. Piracetam, but not Vincamine, reduces the prominent frequency of the theta band in hippocampus during PS. The PS-enhancing effect of the two geriatric drugs may be related to their memory-improving influence.", "contents": "Influence of vincamine and piracetam on sleep--waking pattern of the cat. The effect of Vincamine and Piracetam, two geriatric drugs, on sleep behavior of the laboratory cat was studied. The animals were chronically prepared for recording of the EEG of the cerebral cortex, the lateral geniculate body, and the hippocampus, and for recording of eye movements, the muscular tonus and respiration. During the experiment, sleep and waking behavior were monitored by the above mentioned telemetrically transmitted indicators and also through observation via closed-circuit television. Both Vincamine and Piracetam in doses of 1 and 300 mg/kg p.o., respectively, enhance absolute and relative amounts of paradoxical sleep (PS). Smaller doses have a lesser or no effect on PS. Larger doses again have little effect or else, in the first few hours after application, reduce PS and total amount of sleep. Both drugs have little effect on slow wave and total sleep. Piracetam, but not Vincamine, reduces the prominent frequency of the theta band in hippocampus during PS. The PS-enhancing effect of the two geriatric drugs may be related to their memory-improving influence."}
{"id": "PMID:210854", "title": "Mn2+-electron spin resonance spectra of several lectins.", "content": "Mn2+-ESR spectra of soybean, wax bean and lima bean agglutinin at Q- and X-band frequencies show nearly axially symmetric zero field splitting (ZFS); the dominant anisotropic term of the spin hamiltonian is the quadratic ZFS interaction. There is a relatively large distribution of ZFS parameters. No effects of specific inhibitor (N-acetylgalactosamine) on the soybean agglutinin spectrum were observed. The stoichiometric complex obtained on addition of Mn2+ to a Mn2+-free sample of this protein has a spectrum similar to that of the native protein. The small changes in the spectrum are interpreted in terms of a wider distribution of the ZFS parameters at the Mn binding site. Addition of Ca2+ to Mn2+-soybean agglutinin sharpens the lines, possibly because Ca2+ increases the rigidity of the complex.", "contents": "Mn2+-electron spin resonance spectra of several lectins. Mn2+-ESR spectra of soybean, wax bean and lima bean agglutinin at Q- and X-band frequencies show nearly axially symmetric zero field splitting (ZFS); the dominant anisotropic term of the spin hamiltonian is the quadratic ZFS interaction. There is a relatively large distribution of ZFS parameters. No effects of specific inhibitor (N-acetylgalactosamine) on the soybean agglutinin spectrum were observed. The stoichiometric complex obtained on addition of Mn2+ to a Mn2+-free sample of this protein has a spectrum similar to that of the native protein. The small changes in the spectrum are interpreted in terms of a wider distribution of the ZFS parameters at the Mn binding site. Addition of Ca2+ to Mn2+-soybean agglutinin sharpens the lines, possibly because Ca2+ increases the rigidity of the complex."}
{"id": "PMID:210856", "title": "Effects of herpes virus and amphetamines on locomotor activity.", "content": "Altered levels of catecholamines (dopamine or norepinephrine) or perturbations in their relationship to other neurotransmitter systems (particularly the cholinergic system) have been suggested as causal factors in several human mental disorders. Herpes simplex virus infection of the central nervous system alters catecholamine metabolism and has been suggested to be a causative factor in certain forms of mental illness. As a means of studying chronic HSV infection, we have developed a dual inoculation procedure employing footpad inoculation followed at a 2-week interval by intracerebral challenge with an identical HSV inoculation. In addition, we have employed daily, peripheral injections of d-l-amphetamine to further aid in the study of HSV effects on behavior. Central HSV infection, in the immunized animal, led to a significant decrease in locomotor activity and to an alteration in the response of the infected animal to amphetamine (a shifting of the dose response curve to the right). These results suggest that chronic HSV infection of the CNS leads to a decrease in activity of the catecholaminergic system that may involve either alterations in the release of dopamine and norepinephrine or their effect on postsynaptic receptors.", "contents": "Effects of herpes virus and amphetamines on locomotor activity. Altered levels of catecholamines (dopamine or norepinephrine) or perturbations in their relationship to other neurotransmitter systems (particularly the cholinergic system) have been suggested as causal factors in several human mental disorders. Herpes simplex virus infection of the central nervous system alters catecholamine metabolism and has been suggested to be a causative factor in certain forms of mental illness. As a means of studying chronic HSV infection, we have developed a dual inoculation procedure employing footpad inoculation followed at a 2-week interval by intracerebral challenge with an identical HSV inoculation. In addition, we have employed daily, peripheral injections of d-l-amphetamine to further aid in the study of HSV effects on behavior. Central HSV infection, in the immunized animal, led to a significant decrease in locomotor activity and to an alteration in the response of the infected animal to amphetamine (a shifting of the dose response curve to the right). These results suggest that chronic HSV infection of the CNS leads to a decrease in activity of the catecholaminergic system that may involve either alterations in the release of dopamine and norepinephrine or their effect on postsynaptic receptors."}
{"id": "PMID:210859", "title": "[Activity of Na, K-ATPase and the enzymes of intermediate metabolism in the brains of rats exposed to electroshock].", "content": "Activity of Na, K -ATPase, acetylcholinesterase (AChE) and glutamic acid decarboxylase (GAD) in the fractions of the rat brain and spinal cord tissue were studied in rats during a single electroshock (ES) and 5 and 30 minutes after it. GAD activity of the synaptosome fraction was shown to decrease insignificantly, but activity of AChE, Na, K -ATPase and possibly of proteolytic enzymes increased 5 minutes after electroshock and became normal in 30 minutes. It is supposed that the revealed inhibition of Na, K -ATPase activity in the \"synaptosomes\" of the rat brain cortex could be of pathogenetic significance in the origination of the convulsive process.", "contents": "[Activity of Na, K-ATPase and the enzymes of intermediate metabolism in the brains of rats exposed to electroshock]. Activity of Na, K -ATPase, acetylcholinesterase (AChE) and glutamic acid decarboxylase (GAD) in the fractions of the rat brain and spinal cord tissue were studied in rats during a single electroshock (ES) and 5 and 30 minutes after it. GAD activity of the synaptosome fraction was shown to decrease insignificantly, but activity of AChE, Na, K -ATPase and possibly of proteolytic enzymes increased 5 minutes after electroshock and became normal in 30 minutes. It is supposed that the revealed inhibition of Na, K -ATPase activity in the \"synaptosomes\" of the rat brain cortex could be of pathogenetic significance in the origination of the convulsive process."}
{"id": "PMID:210860", "title": "[Several pathogenetic factors of experimental \"indomethacin\" hypertension].", "content": "The content of cyclic nucleotides (cAMP and cGMP) in the blood plasma, urine and tissues, and also morphological changes of the vascular renal bed were studied in rats with arterial hypertension induced by chronic inhibition of prostaglandin synthesis. A considerable thickening of the wall of the interlobular and arcuate arteries with marked lumen narrowing occurred mainly on account of hypertrophy and the swelling of smooth muscle cells. At the same time there was a marked increase in the cGMP concentration, a decrease of cAMP level, and a reduction of the cAMP/cGMP coefficient in the biological fluids. It is suggested that the changed cyclic nucleotides metabolism is associated with organic and functional changes of the peripheral vascular bed underlying an increase of the total vascular resistance in arterial hypertension.", "contents": "[Several pathogenetic factors of experimental \"indomethacin\" hypertension]. The content of cyclic nucleotides (cAMP and cGMP) in the blood plasma, urine and tissues, and also morphological changes of the vascular renal bed were studied in rats with arterial hypertension induced by chronic inhibition of prostaglandin synthesis. A considerable thickening of the wall of the interlobular and arcuate arteries with marked lumen narrowing occurred mainly on account of hypertrophy and the swelling of smooth muscle cells. At the same time there was a marked increase in the cGMP concentration, a decrease of cAMP level, and a reduction of the cAMP/cGMP coefficient in the biological fluids. It is suggested that the changed cyclic nucleotides metabolism is associated with organic and functional changes of the peripheral vascular bed underlying an increase of the total vascular resistance in arterial hypertension."}
{"id": "PMID:210861", "title": "[Induction of a menadione-dependent respiratory shunt by a platinum complex].", "content": "Submitochondrial particles (SMP) from the bovine heart were treated with platinum complex--K [C2H4 PtCl3] (Zeize's salt); there occurred a menadion-dependent shunt, this being expressed in menadion stimulation of oxygen consumption under conditions of electron transport block with rotenon. This effect was observed only with the use in the capacity of a substrate of NAD.N2, but not of succinate. Menadion-dependent respiration induced with Zeize's salt was dicoumarol-sensitive, but was not inhibited by antimycin and cyanide, this differentiating it from menadionreductase shunt in the intact hepatic mitochondria.", "contents": "[Induction of a menadione-dependent respiratory shunt by a platinum complex]. Submitochondrial particles (SMP) from the bovine heart were treated with platinum complex--K [C2H4 PtCl3] (Zeize's salt); there occurred a menadion-dependent shunt, this being expressed in menadion stimulation of oxygen consumption under conditions of electron transport block with rotenon. This effect was observed only with the use in the capacity of a substrate of NAD.N2, but not of succinate. Menadion-dependent respiration induced with Zeize's salt was dicoumarol-sensitive, but was not inhibited by antimycin and cyanide, this differentiating it from menadionreductase shunt in the intact hepatic mitochondria."}
{"id": "PMID:210862", "title": "[Acetylcholine induced reciprocal changes in the Na, K-ATPase and acetylcholinesterase activity of nerve and membrane preparations of Na, K-ATF-azy].", "content": "ATPase and cholinesterase activities in the homogenate of the frog nerve and membrane Na,K-ATPase preparation of the bovine brain were investigated. Preliminary treatment of the nerve and the preparation by acetylcholine solution (10(-6)--10(-7) M) enhanced their Na,K-ATPase activity and reduced their cholinesterase activity. Possible mechanisms of this phenomenon are discussed.", "contents": "[Acetylcholine induced reciprocal changes in the Na, K-ATPase and acetylcholinesterase activity of nerve and membrane preparations of Na, K-ATF-azy]. ATPase and cholinesterase activities in the homogenate of the frog nerve and membrane Na,K-ATPase preparation of the bovine brain were investigated. Preliminary treatment of the nerve and the preparation by acetylcholine solution (10(-6)--10(-7) M) enhanced their Na,K-ATPase activity and reduced their cholinesterase activity. Possible mechanisms of this phenomenon are discussed."}
{"id": "PMID:210863", "title": "[Effect of apressin, obsidan, diprazine and their combination on the concentration of NAD and NADH2 in the liver and brain of hypoxic rats].", "content": "Apressin (2.5 mg/kg), obsidan (10 mg/kg), and diprazine (10mg/kg) caused an increase in the content of NAD + NAD.H2, without affecting their ratio, in the liver and brain of intact animals. These drugs, taken in the same doses, especially when used together, caused an increase in the NAD + NAD.H2 level; as to NAD/NAD.H2 ratio--it decreased in the state of hypoxia. The authors believe the antihypoxic action of apressin, obsidan, and diprazine to be connected with the rise in the total nicotinamide adenine denucleotide content and with increase of its oxidized form.", "contents": "[Effect of apressin, obsidan, diprazine and their combination on the concentration of NAD and NADH2 in the liver and brain of hypoxic rats]. Apressin (2.5 mg/kg), obsidan (10 mg/kg), and diprazine (10mg/kg) caused an increase in the content of NAD + NAD.H2, without affecting their ratio, in the liver and brain of intact animals. These drugs, taken in the same doses, especially when used together, caused an increase in the NAD + NAD.H2 level; as to NAD/NAD.H2 ratio--it decreased in the state of hypoxia. The authors believe the antihypoxic action of apressin, obsidan, and diprazine to be connected with the rise in the total nicotinamide adenine denucleotide content and with increase of its oxidized form."}
{"id": "PMID:210864", "title": "[Participation of cholinergic mechanisms in realizing the effects of bicuculline].", "content": "Screening and electrophysiological methods were applied to the verification of the hypothesis on a possibility of participation of cholinergic structures in the realization of bicucullin effects. M- and N-cholinolytics (benactizine, atropine, aprophen, and pediphen) failed to arrest the convulsions induced in mice by bicucullin adminstration. At the same time substances inducing accumulation of gamma-aminobutyric acid (GABA) in the brain, i.e. aminooxycetic acid and depakin produced a manifest protective action in convulsions caused by bicucullin administration. In electrophysiological experiments there was also revealed an incapacity of M-cholinolytic benaltizine to arrest the bicucullin effects. Bicucullin proved to diminish depression of the test response in the restoration cycle of the primary response of the rat sensory motor cortex at the intervals of 40--125ms between the stimuli, whereas benactizine decreased the late facilitation of the test response at the intervals of 150--300ms between the stimuli. There was also noted no interaction between benactizine and bicucullin by this test. On the basis of these data a conclusion was drawn that bicucullin effects were caused by the block of postsynaptic GABA receptors, and were not connected with the cholinergic structures activity.", "contents": "[Participation of cholinergic mechanisms in realizing the effects of bicuculline]. Screening and electrophysiological methods were applied to the verification of the hypothesis on a possibility of participation of cholinergic structures in the realization of bicucullin effects. M- and N-cholinolytics (benactizine, atropine, aprophen, and pediphen) failed to arrest the convulsions induced in mice by bicucullin adminstration. At the same time substances inducing accumulation of gamma-aminobutyric acid (GABA) in the brain, i.e. aminooxycetic acid and depakin produced a manifest protective action in convulsions caused by bicucullin administration. In electrophysiological experiments there was also revealed an incapacity of M-cholinolytic benaltizine to arrest the bicucullin effects. Bicucullin proved to diminish depression of the test response in the restoration cycle of the primary response of the rat sensory motor cortex at the intervals of 40--125ms between the stimuli, whereas benactizine decreased the late facilitation of the test response at the intervals of 150--300ms between the stimuli. There was also noted no interaction between benactizine and bicucullin by this test. On the basis of these data a conclusion was drawn that bicucullin effects were caused by the block of postsynaptic GABA receptors, and were not connected with the cholinergic structures activity."}
{"id": "PMID:210865", "title": "[Induction of antibodies to native DNA by components of Bordetella pertussis].", "content": "Administration of Bordetella pertussis and some of their components to mice induced an increase of DNA-binding activity of the sera revealed under ionic strength conditions of physiological saline, mostly on the 14th day. It was shown by the inhibition method that interaction between mouse sera and native DNA was specific. Maximum increase in the quantity of mouse sera proteins reacting with DNA under low ionic strength condition of physiological saline (0.05 M NaCl) is revealed on the 7th day. However, in administration of Bordetella pertussis and their cytoplasmic membrane the elevated DNA-binding proteins content persisted up to 14 days.", "contents": "[Induction of antibodies to native DNA by components of Bordetella pertussis]. Administration of Bordetella pertussis and some of their components to mice induced an increase of DNA-binding activity of the sera revealed under ionic strength conditions of physiological saline, mostly on the 14th day. It was shown by the inhibition method that interaction between mouse sera and native DNA was specific. Maximum increase in the quantity of mouse sera proteins reacting with DNA under low ionic strength condition of physiological saline (0.05 M NaCl) is revealed on the 7th day. However, in administration of Bordetella pertussis and their cytoplasmic membrane the elevated DNA-binding proteins content persisted up to 14 days."}
{"id": "PMID:210866", "title": "[Quantitative analysis of the immunogenic activity of SV40 virus and the cells of tumors induced by this virus].", "content": "The study of specific antitumour immunity induced by onogenic SV40 virus and by cell of SV40 virus and by cells of SV40-induced tumour of Syrian hamster demonstrated direct correlation between the level of specific antitumour resistance and the immunizing virus and tumour cell doses. The minimal resistance-inducing dose of the wild type SV40 virus strain was 10 times higher than that of ts A-30 mutant of this virus. Minimal resistance-inducing dose of irradiated cells of the tumour was about 9 x 10(5) cells; a 10-fold increase of this dose significantly increased the specific antitumour immunity level.", "contents": "[Quantitative analysis of the immunogenic activity of SV40 virus and the cells of tumors induced by this virus]. The study of specific antitumour immunity induced by onogenic SV40 virus and by cell of SV40 virus and by cells of SV40-induced tumour of Syrian hamster demonstrated direct correlation between the level of specific antitumour resistance and the immunizing virus and tumour cell doses. The minimal resistance-inducing dose of the wild type SV40 virus strain was 10 times higher than that of ts A-30 mutant of this virus. Minimal resistance-inducing dose of irradiated cells of the tumour was about 9 x 10(5) cells; a 10-fold increase of this dose significantly increased the specific antitumour immunity level."}
{"id": "PMID:210867", "title": "[Comparative immunogenicity of irradiated and nonirradiated syngeneic and xenogeneic tumor cells containing a common specific transplantation antigen].", "content": "The authors compared the immunogenic activity for Syrian hamsters of native and irradiated syngeneic and xenogeneic tumour cells bearing on their surface common and SV40-specific transplantational antigen. The results obtained showed syngeneic tumour cells to be more immunogenic for the recipient than the xenogeneic tumour cells containing an antigen of the same specificity. Irradiation renders tumour cells, including the xenogeneic ones, more immunogenic, this possibly being associated with the capacity of nonirradiated cells to escape from immune recognition through their ability to divide.", "contents": "[Comparative immunogenicity of irradiated and nonirradiated syngeneic and xenogeneic tumor cells containing a common specific transplantation antigen]. The authors compared the immunogenic activity for Syrian hamsters of native and irradiated syngeneic and xenogeneic tumour cells bearing on their surface common and SV40-specific transplantational antigen. The results obtained showed syngeneic tumour cells to be more immunogenic for the recipient than the xenogeneic tumour cells containing an antigen of the same specificity. Irradiation renders tumour cells, including the xenogeneic ones, more immunogenic, this possibly being associated with the capacity of nonirradiated cells to escape from immune recognition through their ability to divide."}
{"id": "PMID:210868", "title": "Subpopulation of human tonsillar lymphocytes with mitochondria visible by light microscopy.", "content": "We observed a subpopulation of human tonsillar lymphocytes with cytoplasmic inclusions that stained orthochromatically blue with Wright stain. These lymphocytes represented fewer than 2% of cells in suspensions of cells from most tonsils; however, suspensions of tonsillar cells from 4 to 18 studied patients contained more than 2% (2.8%--6.4%) lymphocytes with cytoplasmic inclusions. These cells sedimented less rapidly than the modal population of lymphocytes in a previously described isokinetic gradient. Histochemical and ultrastructural studies suggested that the stained inclusions were prominent mitochondria stained by the Wright stain.", "contents": "Subpopulation of human tonsillar lymphocytes with mitochondria visible by light microscopy. We observed a subpopulation of human tonsillar lymphocytes with cytoplasmic inclusions that stained orthochromatically blue with Wright stain. These lymphocytes represented fewer than 2% of cells in suspensions of cells from most tonsils; however, suspensions of tonsillar cells from 4 to 18 studied patients contained more than 2% (2.8%--6.4%) lymphocytes with cytoplasmic inclusions. These cells sedimented less rapidly than the modal population of lymphocytes in a previously described isokinetic gradient. Histochemical and ultrastructural studies suggested that the stained inclusions were prominent mitochondria stained by the Wright stain."}
{"id": "PMID:210869", "title": "Presence of hormonally-sensitive adenylate cyclase receptors in capillary-enriched fractions from rat cerebral cortex.", "content": "The 10 000 g particulate fraction from capillary-enriched fractions isolated from rat cerebral cortex was shown to possess an adenylate cyclase highly sensitive to activation by sodium fluoride, norepinephrine, epinephrine, isoproterenol and dopamine. To a lesser extent histamine and three dopamine agonists, namely M-7 (5,6-dihydroxy-2-dimethylamino tetralin), ET-495 (methane sulfonate of pyribedil), and S-584 (metabolite of pyribedil) stimulated the enzyme preparation. The action of norepinephrine was blocked by propanolol while phenotolamine and haloperidol were relatively ineffective except at highest concentrations. Phentolamine and propanolol at only highest concentrations (10(-4) M) antagonized the action of dopamine. Haloperidol was seen to be a potent inhibitor of either dopamine- or dopamine agonist-sensitive adenylate cyclase. No effects on the enzyme were observed with methoxamine, octopamine or serotonin. These preliminary data suggest the presence of a mixed population of receptors for adenylate cyclase in rat brain capillaries.", "contents": "Presence of hormonally-sensitive adenylate cyclase receptors in capillary-enriched fractions from rat cerebral cortex. The 10 000 g particulate fraction from capillary-enriched fractions isolated from rat cerebral cortex was shown to possess an adenylate cyclase highly sensitive to activation by sodium fluoride, norepinephrine, epinephrine, isoproterenol and dopamine. To a lesser extent histamine and three dopamine agonists, namely M-7 (5,6-dihydroxy-2-dimethylamino tetralin), ET-495 (methane sulfonate of pyribedil), and S-584 (metabolite of pyribedil) stimulated the enzyme preparation. The action of norepinephrine was blocked by propanolol while phenotolamine and haloperidol were relatively ineffective except at highest concentrations. Phentolamine and propanolol at only highest concentrations (10(-4) M) antagonized the action of dopamine. Haloperidol was seen to be a potent inhibitor of either dopamine- or dopamine agonist-sensitive adenylate cyclase. No effects on the enzyme were observed with methoxamine, octopamine or serotonin. These preliminary data suggest the presence of a mixed population of receptors for adenylate cyclase in rat brain capillaries."}
{"id": "PMID:210874", "title": "Differences in dihydroergotamine antagonism of glucose release by catecholamines, glucagon and adenosine 3',5'-monophosphate in rabbit liver slices.", "content": "1 Quantitative studies were made on the glucose release from rabbit liver slices in vitro induced by a range of concentrations of (-)-adrenaline (Ad), (-)-isoprenaline (Iso), glucagon and adenosine 3',5'-monophosphate (cyclic AMP) in the presence and absence of several concentrations of dihydroergotamine (DHE). 2 DHE (3.16 X 10(-6) M) shifted the Ad log concentration-response (LCR) curve to the right and also reduced the maximum response; at a higher concentration (3.16 x 10(-5) M) it produced a greater shift to the right of the LCR curve and caused a reduction in the slope and a larger depression of the maximal responses. The LCR curve to Iso was similarly affected by this higher concentration of DHE. 3 DHE (1  X 10(-5) M) produced no significant effect on the LCR curves of glucagon or cyclic AMP and even at 1 x 10(-4) M DHE caused only a slight depression of the maximal responses to both agonists without any modification of the lower major portions of the curves. 4 These data indicate a selective antagonism by DHE at the rabbit liver adrenoceptor and, since the maximal responses to catecholamines were depressed by a lower concentration of DHE than was required to produce a slight depression of the responses to glucagon and cyclic AMP, the antagonism of DHE against catecholamines does not appear to be at a site beyond the formation of cyclic AMP, but rather at a site more intimately related to the adrenoceptor.", "contents": "Differences in dihydroergotamine antagonism of glucose release by catecholamines, glucagon and adenosine 3',5'-monophosphate in rabbit liver slices. 1 Quantitative studies were made on the glucose release from rabbit liver slices in vitro induced by a range of concentrations of (-)-adrenaline (Ad), (-)-isoprenaline (Iso), glucagon and adenosine 3',5'-monophosphate (cyclic AMP) in the presence and absence of several concentrations of dihydroergotamine (DHE). 2 DHE (3.16 X 10(-6) M) shifted the Ad log concentration-response (LCR) curve to the right and also reduced the maximum response; at a higher concentration (3.16 x 10(-5) M) it produced a greater shift to the right of the LCR curve and caused a reduction in the slope and a larger depression of the maximal responses. The LCR curve to Iso was similarly affected by this higher concentration of DHE. 3 DHE (1  X 10(-5) M) produced no significant effect on the LCR curves of glucagon or cyclic AMP and even at 1 x 10(-4) M DHE caused only a slight depression of the maximal responses to both agonists without any modification of the lower major portions of the curves. 4 These data indicate a selective antagonism by DHE at the rabbit liver adrenoceptor and, since the maximal responses to catecholamines were depressed by a lower concentration of DHE than was required to produce a slight depression of the responses to glucagon and cyclic AMP, the antagonism of DHE against catecholamines does not appear to be at a site beyond the formation of cyclic AMP, but rather at a site more intimately related to the adrenoceptor."}
{"id": "PMID:210875", "title": "The effect of stimulus intensity on alpha-adrenoceptor-mediated feedback control of noradrenaline release.", "content": "1 Mouse vas deferns stimulated transmurally (2.5 Hz, 2-32 V, 40-620 mA, FOR 45 s) responded with a twitch and a secondary contraction. Both responses were abolished by cinchocaine and were voltage-dependent. 2 In tissues previously incubated with (3H)-(--)-noradrenaline, stimulation also produced an increase in tritium overflow from the tissue. Phentolamine increased tritium overflow by 19% at high stimulus intensities (30 V, 600 mA) and by 130% at low stimulus intensities (11 V, 200 mA). 3 It is concluded that alpha-adrenoceptor-mediated feedback control of noradrenaline release is more marked at low stimulus intensities and that this is compatible with a role for calcium ions in this control mechanism.", "contents": "The effect of stimulus intensity on alpha-adrenoceptor-mediated feedback control of noradrenaline release. 1 Mouse vas deferns stimulated transmurally (2.5 Hz, 2-32 V, 40-620 mA, FOR 45 s) responded with a twitch and a secondary contraction. Both responses were abolished by cinchocaine and were voltage-dependent. 2 In tissues previously incubated with (3H)-(--)-noradrenaline, stimulation also produced an increase in tritium overflow from the tissue. Phentolamine increased tritium overflow by 19% at high stimulus intensities (30 V, 600 mA) and by 130% at low stimulus intensities (11 V, 200 mA). 3 It is concluded that alpha-adrenoceptor-mediated feedback control of noradrenaline release is more marked at low stimulus intensities and that this is compatible with a role for calcium ions in this control mechanism."}
{"id": "PMID:210876", "title": "Severity of coronary atherosclerosis related to lipoprotein concentration.", "content": "The influence of individual lipoproteins on the severity of coronary atherosclerosis was studied in 41 patients undergoing coronary angiography. The extent of athero-sclerosis was quantified by a coronary atherosclerosis score (CAS) based on the number and severity of lesions in eight proximal segments of the coronary circulation. The concentration of high-density lipoprotein (HDL) showed a strong inverse association with CAS, which was independent of the effects of age and other lipoproteins. On multivariate analysis concentrations of other lipids--namely, total plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and the combined effect of LDL cholesterol plus very-low-density lipoprotein triglyceride--showed direct, significant correlations with CAS, but these were weaker than that of HDL. This study shows that concentrations of several circulating lipoproteins are related to the severity of coronary atherosclerosis, HDL having an apparent retarding effect. These findings may partly explain the influence of lipoproteins on the development of clinical coronary heart disease.", "contents": "Severity of coronary atherosclerosis related to lipoprotein concentration. The influence of individual lipoproteins on the severity of coronary atherosclerosis was studied in 41 patients undergoing coronary angiography. The extent of athero-sclerosis was quantified by a coronary atherosclerosis score (CAS) based on the number and severity of lesions in eight proximal segments of the coronary circulation. The concentration of high-density lipoprotein (HDL) showed a strong inverse association with CAS, which was independent of the effects of age and other lipoproteins. On multivariate analysis concentrations of other lipids--namely, total plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and the combined effect of LDL cholesterol plus very-low-density lipoprotein triglyceride--showed direct, significant correlations with CAS, but these were weaker than that of HDL. This study shows that concentrations of several circulating lipoproteins are related to the severity of coronary atherosclerosis, HDL having an apparent retarding effect. These findings may partly explain the influence of lipoproteins on the development of clinical coronary heart disease."}
{"id": "PMID:210878", "title": "Effect of opioid peptides on L-noradrenaline-stimulated cyclic AMP formation in homogenates of rat cerebral cortex and hypothalamus.", "content": "Morphine and the opioid peptides leucine-enkephalin (leu-enk), methionine-enkephalin (met-enk) and beta-endorphin had no effect on basal cyclic AMP levels in rat cerebral cortex and hypothalamus, but each inhibited noradrenaline (NA)-stimulated cyclic AMP formation in both brain regions. This inhibition was reversed by naloxone. Naloxone did not reverse phentolamine- or propranolol-induced inhibition of NA-stimulated cyclic AMP formation. The increase in cyclic AMP formation induced by NaF or MnCl2 was unaffected by met-enk or morphine. These data suggest that in rat cerebral cortex and hypothalamus opiates bind to opiate receptors and that the opiate-receptor complex interferes with noradrenergic receptor activity.", "contents": "Effect of opioid peptides on L-noradrenaline-stimulated cyclic AMP formation in homogenates of rat cerebral cortex and hypothalamus. Morphine and the opioid peptides leucine-enkephalin (leu-enk), methionine-enkephalin (met-enk) and beta-endorphin had no effect on basal cyclic AMP levels in rat cerebral cortex and hypothalamus, but each inhibited noradrenaline (NA)-stimulated cyclic AMP formation in both brain regions. This inhibition was reversed by naloxone. Naloxone did not reverse phentolamine- or propranolol-induced inhibition of NA-stimulated cyclic AMP formation. The increase in cyclic AMP formation induced by NaF or MnCl2 was unaffected by met-enk or morphine. These data suggest that in rat cerebral cortex and hypothalamus opiates bind to opiate receptors and that the opiate-receptor complex interferes with noradrenergic receptor activity."}
{"id": "PMID:210879", "title": "Pharmacological analysis of analgesia and self-stimulation elicited by electrical stimulation of catecholamine nuclei in the rat brain.", "content": "The relationship between intracranial self-stimulation (ICSS) and stimulation-produced analgesia (SPA) was investigated in that rat employing an operant bar-press response and a modification of the hot-plate test. ICSS and SPA were elicited through bipolar electrodes chronically implanted in two catecholamine nuclei; the nucleus locus coeruleus (LC) and the substantia nigra (SN). These sites have previously been shown to yield both phenomena. SPA was shown to be of a magnitude similar to that of morphine. In addition, SPA deriving from both LC and SN was significantly reversed by the specific opiate antagonist, naloxone. The intensity of the stimulating current sufficient to induce SPA was found to be higher than that required for ICSS. The pharmacological susceptibilities of the two phenomena were tested by administering a number of drugs: haloperidol, propranolol, pimozide and AMPT attenuated ICSS in both LC and SN, while leaving SPA unaffected. In contrast, methysergide and PCPA blocked SPA and simultaneously facilitated ICSS. The present results indicate a dissociation of ICSS and SPA from LC and SN at both physiological and neurochemical levels; ICSS rates appeared to be a function of catecholaminergic tone, while SPA depended upon the integrity of serotonin transmission.", "contents": "Pharmacological analysis of analgesia and self-stimulation elicited by electrical stimulation of catecholamine nuclei in the rat brain. The relationship between intracranial self-stimulation (ICSS) and stimulation-produced analgesia (SPA) was investigated in that rat employing an operant bar-press response and a modification of the hot-plate test. ICSS and SPA were elicited through bipolar electrodes chronically implanted in two catecholamine nuclei; the nucleus locus coeruleus (LC) and the substantia nigra (SN). These sites have previously been shown to yield both phenomena. SPA was shown to be of a magnitude similar to that of morphine. In addition, SPA deriving from both LC and SN was significantly reversed by the specific opiate antagonist, naloxone. The intensity of the stimulating current sufficient to induce SPA was found to be higher than that required for ICSS. The pharmacological susceptibilities of the two phenomena were tested by administering a number of drugs: haloperidol, propranolol, pimozide and AMPT attenuated ICSS in both LC and SN, while leaving SPA unaffected. In contrast, methysergide and PCPA blocked SPA and simultaneously facilitated ICSS. The present results indicate a dissociation of ICSS and SPA from LC and SN at both physiological and neurochemical levels; ICSS rates appeared to be a function of catecholaminergic tone, while SPA depended upon the integrity of serotonin transmission."}
{"id": "PMID:210882", "title": "Effects of 4-aminopyridine on neuromuscular transmission.", "content": "4-Aminopyridine (4-AP) powerfully increases transmitter release from motor nerve terminals of rat and frog skeletal muscle in response to single nerve impulses. The drug also enhances transmitter release during repetitive nerve activity but, at D-tubocurarine-blocked endplates, only the first impulses cause increased transmitter release at stimulation frequencies at or above 50 Hz. At magnesium- and botulinum-poisoned endplates, 4-AP potentiates transmitter release at every stimulus during tetanic nerve stimulation and restores neuromuscular transmission. Spontaneous transmitter release in the rat is not affected by the drug, but at some frog endplates miniature endplate potential (mepp) frequency increases. The drug has no post-synaptic action, as evidenced by its lack of effect on amplitude or time course of mepps. Decreasing the temperature from 37 to 15 degrees C does not abolish the effect of 4-AP on neuromuscular transmission. In the presence of 4-AP, single nerve impulses produce repetitive spontaneous activity in the nerve terminal of the frog nerve-muscle preparation. Experiments on the mode of action of 4-AP suggest that the drug increases transmitter release by enhancing the influx of calcium ions during depolarization of the nerve terminal.", "contents": "Effects of 4-aminopyridine on neuromuscular transmission. 4-Aminopyridine (4-AP) powerfully increases transmitter release from motor nerve terminals of rat and frog skeletal muscle in response to single nerve impulses. The drug also enhances transmitter release during repetitive nerve activity but, at D-tubocurarine-blocked endplates, only the first impulses cause increased transmitter release at stimulation frequencies at or above 50 Hz. At magnesium- and botulinum-poisoned endplates, 4-AP potentiates transmitter release at every stimulus during tetanic nerve stimulation and restores neuromuscular transmission. Spontaneous transmitter release in the rat is not affected by the drug, but at some frog endplates miniature endplate potential (mepp) frequency increases. The drug has no post-synaptic action, as evidenced by its lack of effect on amplitude or time course of mepps. Decreasing the temperature from 37 to 15 degrees C does not abolish the effect of 4-AP on neuromuscular transmission. In the presence of 4-AP, single nerve impulses produce repetitive spontaneous activity in the nerve terminal of the frog nerve-muscle preparation. Experiments on the mode of action of 4-AP suggest that the drug increases transmitter release by enhancing the influx of calcium ions during depolarization of the nerve terminal."}
{"id": "PMID:210883", "title": "Petide antagonists of the renin-angiotensin system in the characterisation of receptors for angiotensin-induced drinking.", "content": "The two naturally occurring analogues of angiotensin II (AII), Asp1-Val5-AII and Asp1-Ile5-AII, were equally effective as intracranial dipsogens in the water-replete rat. Renin, synthetic tetradecapeptide renin substrate (SRS) and angiotensin I (AI) also produced copious drinking when injected into the brain, but the naturally occurring renin substrate of rat caused little drinking and was much less effective than SRS. Prior intracranial injection of pepstatin, a competitive antagonist of the renin-angiotensinogen reaction, reduced drinking in response to renin and SRS but not to AI and AII. Renin-, SRS- and AI-induced drinking were inhibited by the converting enzyme inhibitor SQ 20881 injected through the same intracranial cannula in antagonist to agonist ratio of 1000:1, whereas the AII response was enhanced, although not significantly so, and the carbachol response was unaffected. Finally, position 8 aliphatic substituted analogues of AII were competitive antagonists of AII-induced drinking, and also inhibited drinking induced by renin, SRS and AI injected through the same intracranial cannula, but they did not inhibit carbachol-induced drinking. In conclusion, the angiotensin-sensitive receptor for thirst does not accept SRS or AI. It responds best to AII.", "contents": "Petide antagonists of the renin-angiotensin system in the characterisation of receptors for angiotensin-induced drinking. The two naturally occurring analogues of angiotensin II (AII), Asp1-Val5-AII and Asp1-Ile5-AII, were equally effective as intracranial dipsogens in the water-replete rat. Renin, synthetic tetradecapeptide renin substrate (SRS) and angiotensin I (AI) also produced copious drinking when injected into the brain, but the naturally occurring renin substrate of rat caused little drinking and was much less effective than SRS. Prior intracranial injection of pepstatin, a competitive antagonist of the renin-angiotensinogen reaction, reduced drinking in response to renin and SRS but not to AI and AII. Renin-, SRS- and AI-induced drinking were inhibited by the converting enzyme inhibitor SQ 20881 injected through the same intracranial cannula in antagonist to agonist ratio of 1000:1, whereas the AII response was enhanced, although not significantly so, and the carbachol response was unaffected. Finally, position 8 aliphatic substituted analogues of AII were competitive antagonists of AII-induced drinking, and also inhibited drinking induced by renin, SRS and AI injected through the same intracranial cannula, but they did not inhibit carbachol-induced drinking. In conclusion, the angiotensin-sensitive receptor for thirst does not accept SRS or AI. It responds best to AII."}
{"id": "PMID:210888", "title": "Effects of estrogen and progesterone on plasma gonadotropins and on catecholamine levels and turnover in discrete brain regions of ovariectomized rats.", "content": "Estradiol benzoate (EB) was administered, either alone or followed 48 h later by progesterone to ovariectomized rats. Plasma gonadotropins (FSH and LH) and steady state levels of norepinephrine (NE) and dopamine (DA) in 17 individual brain nuclei were assayed. In addition, catecholamines were measured after administration of the synthesis inhibitor alpha-methyltyrosine (alpha-MT) in order to assess hormonal influences on turnover. Treatment with EB, which lowered plasma FSH and LH, reduced the depletion of NE produced by alpha-MT in the lateral septum, interstitial nucleus of the stria terminalis, and central gray catecholamine area, and reduced the depletion of DA in the nucleus of the tractus diagonalis. EB enhanced NE depletion in the periventricular and anterior hypothalamic nuclei, and raised steady state levels of NE in the medial amygdaloid nucleus. These effects were reversed by subsequent treatment with progesterone, which stimulated FSH and LH release. EB plus progesterone enhanced the alpha-MT-induced depletion of NE over that observed with EB alone in the arcuate nucleus, and similarly enhanced DA depletion in the interstitial nucleus of the stria terminalis. EB plus progesterone prevented the depletion of NE by alpha-MT in the paraventricular and ventromedial nuclei, and also lowered resting NE levels in the paraventricular nucleus. The results suggest that catecholamine neurons in several discrete brain regions participate in the stimulatory and inhibitory feedback effects of ovarian hormones on gonadotropin secretion, and perhaps also on the hormonal induction of sexual receptivity.", "contents": "Effects of estrogen and progesterone on plasma gonadotropins and on catecholamine levels and turnover in discrete brain regions of ovariectomized rats. Estradiol benzoate (EB) was administered, either alone or followed 48 h later by progesterone to ovariectomized rats. Plasma gonadotropins (FSH and LH) and steady state levels of norepinephrine (NE) and dopamine (DA) in 17 individual brain nuclei were assayed. In addition, catecholamines were measured after administration of the synthesis inhibitor alpha-methyltyrosine (alpha-MT) in order to assess hormonal influences on turnover. Treatment with EB, which lowered plasma FSH and LH, reduced the depletion of NE produced by alpha-MT in the lateral septum, interstitial nucleus of the stria terminalis, and central gray catecholamine area, and reduced the depletion of DA in the nucleus of the tractus diagonalis. EB enhanced NE depletion in the periventricular and anterior hypothalamic nuclei, and raised steady state levels of NE in the medial amygdaloid nucleus. These effects were reversed by subsequent treatment with progesterone, which stimulated FSH and LH release. EB plus progesterone enhanced the alpha-MT-induced depletion of NE over that observed with EB alone in the arcuate nucleus, and similarly enhanced DA depletion in the interstitial nucleus of the stria terminalis. EB plus progesterone prevented the depletion of NE by alpha-MT in the paraventricular and ventromedial nuclei, and also lowered resting NE levels in the paraventricular nucleus. The results suggest that catecholamine neurons in several discrete brain regions participate in the stimulatory and inhibitory feedback effects of ovarian hormones on gonadotropin secretion, and perhaps also on the hormonal induction of sexual receptivity."}
{"id": "PMID:210896", "title": "Effects of opiates and methionine-enkephalin on pontine and bulbar respiratory neurones of the cat.", "content": "The effects of microelectrophoretically applied opiate agonists and the antagonist naloxone have been investigated on extracellularly recorded neurones in pontine and bulbar respiratory centers of the cat. Morphine, levorphanol and methionine-enkephalin depressed the spontaneous discharge of respiration related units and the firing induced in these cells by phoretically applied L-glutamate. The rhythmic pattern of these neurones was modified, in such a way that basal activity was hardly affected while peak frequency was markedly reduced. These effects are mediated via stereospecific opiate receptors, since they were antagonized by naloxone and not mimicked by the D+ enantiomer of levorphanol, dextrophan. The few excitations observed following opiate agonist application were not antagonizable by naloxone. These data may provide a basis for the explanation of the depressant effect on central respiratory rhythm of systemically injected opiates which have been obtained in control experiments. The results are interpreted in terms of opiates lowering excitatory synaptic efficacy.", "contents": "Effects of opiates and methionine-enkephalin on pontine and bulbar respiratory neurones of the cat. The effects of microelectrophoretically applied opiate agonists and the antagonist naloxone have been investigated on extracellularly recorded neurones in pontine and bulbar respiratory centers of the cat. Morphine, levorphanol and methionine-enkephalin depressed the spontaneous discharge of respiration related units and the firing induced in these cells by phoretically applied L-glutamate. The rhythmic pattern of these neurones was modified, in such a way that basal activity was hardly affected while peak frequency was markedly reduced. These effects are mediated via stereospecific opiate receptors, since they were antagonized by naloxone and not mimicked by the D+ enantiomer of levorphanol, dextrophan. The few excitations observed following opiate agonist application were not antagonizable by naloxone. These data may provide a basis for the explanation of the depressant effect on central respiratory rhythm of systemically injected opiates which have been obtained in control experiments. The results are interpreted in terms of opiates lowering excitatory synaptic efficacy."}
{"id": "PMID:210897", "title": "Differential effects of spinal cord lesions on narcotic and non-narcotic suppression of nociceptive reflexes: further evidence for the physiologic multiplicity of pain modulation.", "content": "These studies examined the effects of bilateral lesions of the dorsolateral funiculus (DLF) of the rat spinal cord on the inhibition of a nociceptive reflex produced either by a systemic injection of 4 mg/kg of morphine or by a 20 sec exposure to 1.0 mA of transcutaneous electric shock. Reflex inhibition was quantified and analgesia inferred by use of a modified version of the D'Amour-Smith tail-flick test. Lesions which included only the DLF reduced morphine-produced analgesia (MA) by 73% but had no effect on shock-produced analgesia (SA) observed in the same rats. Baseline tail-flick latencies of this group were not affected by the lesions. Control lesions restricted to the dorsal columns attenuated neither MA nor SA. Lesions which included both the dorsal columns and DLF did not affect SA and produced no greater reduction in MA than lesions of the DLF alone. Previous work indicates that both MA and SA result, at least in part, from supraspinal activity. The current data indicate that: (1) supraspinal modulation participating in two different types of analgesic induction involves separate descending spinal pathways and (2) the maximal expression of analgesia produced by administration of narcotics requires the integrity of a supraspinal neural system projecting in the DLF.", "contents": "Differential effects of spinal cord lesions on narcotic and non-narcotic suppression of nociceptive reflexes: further evidence for the physiologic multiplicity of pain modulation. These studies examined the effects of bilateral lesions of the dorsolateral funiculus (DLF) of the rat spinal cord on the inhibition of a nociceptive reflex produced either by a systemic injection of 4 mg/kg of morphine or by a 20 sec exposure to 1.0 mA of transcutaneous electric shock. Reflex inhibition was quantified and analgesia inferred by use of a modified version of the D'Amour-Smith tail-flick test. Lesions which included only the DLF reduced morphine-produced analgesia (MA) by 73% but had no effect on shock-produced analgesia (SA) observed in the same rats. Baseline tail-flick latencies of this group were not affected by the lesions. Control lesions restricted to the dorsal columns attenuated neither MA nor SA. Lesions which included both the dorsal columns and DLF did not affect SA and produced no greater reduction in MA than lesions of the DLF alone. Previous work indicates that both MA and SA result, at least in part, from supraspinal activity. The current data indicate that: (1) supraspinal modulation participating in two different types of analgesic induction involves separate descending spinal pathways and (2) the maximal expression of analgesia produced by administration of narcotics requires the integrity of a supraspinal neural system projecting in the DLF."}
{"id": "PMID:210900", "title": "[Bioligical aspects of cell fusion induced in vitro by sheep Visna virus].", "content": "Visna virus induced cell fusion of sheep choroid plexus cells was explored in vitro. Fusion is early rapid, and of exogenous origin for multiplicities of infection equal to or greater than 2 UFP per cell; whereas fusion is slow, late-occurring and of endogenous origin for multiplicities of infection less than or equal to 0.75 UFP per cell.", "contents": "[Bioligical aspects of cell fusion induced in vitro by sheep Visna virus]. Visna virus induced cell fusion of sheep choroid plexus cells was explored in vitro. Fusion is early rapid, and of exogenous origin for multiplicities of infection equal to or greater than 2 UFP per cell; whereas fusion is slow, late-occurring and of endogenous origin for multiplicities of infection less than or equal to 0.75 UFP per cell."}
{"id": "PMID:210901", "title": "[Kinetics and ultrastructure of sheep fibroblast fusion induced by polyethylene glycol. Comparison with endogenous cell fusion induced by Visna virus].", "content": "The authors compare the fusion of sheep fibroblasts induced by low multiplicities of infection using visna virus and by high concentrations of polyethylene-glycol. In the case of Visna virus cell fusion is of the endogenous type, while fusion induced by polyethylene-glycol is of the exogenous type. The ultrastructural features are discussed for each type of cell fusion. The main differences between the two systems involve the intracellular microfilaments and Golgi apparatus.", "contents": "[Kinetics and ultrastructure of sheep fibroblast fusion induced by polyethylene glycol. Comparison with endogenous cell fusion induced by Visna virus]. The authors compare the fusion of sheep fibroblasts induced by low multiplicities of infection using visna virus and by high concentrations of polyethylene-glycol. In the case of Visna virus cell fusion is of the endogenous type, while fusion induced by polyethylene-glycol is of the exogenous type. The ultrastructural features are discussed for each type of cell fusion. The main differences between the two systems involve the intracellular microfilaments and Golgi apparatus."}
{"id": "PMID:210903", "title": "[Study of cyclic AMP in rat tissue during the phase of hypocalcemic activity of parathyroid hormone].", "content": "As soon as two minutes after PTH i.v. injection the blood and kidney AMPc level is maximally increased but the lowering blood calcium effect remained till to ten minutes. At this time the calvaria AMPc level reached its maximum just at the onset of hypercalcemic effect of PTH. Thus AMPc increase in tissues is consistent with the two opposite effects of PTH.", "contents": "[Study of cyclic AMP in rat tissue during the phase of hypocalcemic activity of parathyroid hormone]. As soon as two minutes after PTH i.v. injection the blood and kidney AMPc level is maximally increased but the lowering blood calcium effect remained till to ten minutes. At this time the calvaria AMPc level reached its maximum just at the onset of hypercalcemic effect of PTH. Thus AMPc increase in tissues is consistent with the two opposite effects of PTH."}
{"id": "PMID:210904", "title": "[Mitochondrial localization of cytochrome c1 with specific antibodies].", "content": "A specific antibody against cytochrome c1 (pig heart mitochondria) has been obtained. It inhibits the electron transport of the respiratory chain in the intact mitochondria at the cytochrome c1 site of inner mitochondrial membrane ; but it has no effect on the isolated submitochondrial particles (inside-out inner mitochondrial membrane vesicles free of any outer membrane or outside-out inner membrane). Thus the topologic position of cytochrome c1 in the inner mitochondrial membrane is asymetrically lcoated on the outer side of the inner mitochondrial membrane. These results agree with our previous researches on ATP-ase and cytochromes b, c and a, indicating the location on the inner side for the first one, transmembranous for the last one, on the outer side for the others respiratory chain components. Thus the electron transport from cytochrome b to a takes place in the outer region of inner mitochondrial membrane and the transmembranous location of cytochrome-oxidase facilitates the transfer of the electrons to oxygen.", "contents": "[Mitochondrial localization of cytochrome c1 with specific antibodies]. A specific antibody against cytochrome c1 (pig heart mitochondria) has been obtained. It inhibits the electron transport of the respiratory chain in the intact mitochondria at the cytochrome c1 site of inner mitochondrial membrane ; but it has no effect on the isolated submitochondrial particles (inside-out inner mitochondrial membrane vesicles free of any outer membrane or outside-out inner membrane). Thus the topologic position of cytochrome c1 in the inner mitochondrial membrane is asymetrically lcoated on the outer side of the inner mitochondrial membrane. These results agree with our previous researches on ATP-ase and cytochromes b, c and a, indicating the location on the inner side for the first one, transmembranous for the last one, on the outer side for the others respiratory chain components. Thus the electron transport from cytochrome b to a takes place in the outer region of inner mitochondrial membrane and the transmembranous location of cytochrome-oxidase facilitates the transfer of the electrons to oxygen."}
{"id": "PMID:210905", "title": "[Presence of nuclear triiodothyronine (T3) receptors in mouse fibroblasts].", "content": "The present preliminary data obtained from intact fibroblasts of adult mice (polyploid stem L 929) suggest that this cell system possesses high-affinity and saturable nuclear binding sites for triiodothyronine. As estimated by the Scatchard analysis, the equilibrium dissociation constant is approximately 2 X 10(-10) moles, the maximal binding capacity is about 2 000 sites for T3 per cell nucleus.", "contents": "[Presence of nuclear triiodothyronine (T3) receptors in mouse fibroblasts]. The present preliminary data obtained from intact fibroblasts of adult mice (polyploid stem L 929) suggest that this cell system possesses high-affinity and saturable nuclear binding sites for triiodothyronine. As estimated by the Scatchard analysis, the equilibrium dissociation constant is approximately 2 X 10(-10) moles, the maximal binding capacity is about 2 000 sites for T3 per cell nucleus."}
{"id": "PMID:210906", "title": "Regulation of the diurnal cycle in activity of serotonin acetyltransferase in the chick pineal gland.", "content": "When chick pineal glands were explanted into organ culture at midlight phase of a diurnal cycle of illumination and incubated in the dark, they developed marked increases in serotonin acetyltransferase (acetyl coA:arylamine N-acetyltransferase; EC 2.3.1.5) activity. Either this increase in activity was inhibited or its onset was retarded in glands incubated under constant illumination. Supplements of theophylline, isobutylmethylxanthine, quinidine, and compound Ro 20-1724 (4-(3-butoxyl-4-methoxybenzyl)-2-imidazolidinone) elicited very marked increases in serotonin acetyltransferase activity in glands cultured in the dark. Levels of activity attained after 6 h in culture approached or exceeded the maximum levels attained at middark phase of the diurnal cycle in vivo. Effects of theophylline and compound Ro 20-1724 were additive. Supplements of dibutryl cAMP had little or no effect upon levels of serotonin acetyltransferase activity when tested alone or in combination with theophylline but further enhanced the increase in the level of enzyme activity elicited by Ro 20-1724. Adenosine and cAMP had little or no effect upon levels of serotonin acetyltransferase activity. It is concluded that levels of serotonin acetyltransferase activity in the chick pineal gland are regulated by a repressive, negative-control mechanism, which probably involves a membranous adenosine receptor.", "contents": "Regulation of the diurnal cycle in activity of serotonin acetyltransferase in the chick pineal gland. When chick pineal glands were explanted into organ culture at midlight phase of a diurnal cycle of illumination and incubated in the dark, they developed marked increases in serotonin acetyltransferase (acetyl coA:arylamine N-acetyltransferase; EC 2.3.1.5) activity. Either this increase in activity was inhibited or its onset was retarded in glands incubated under constant illumination. Supplements of theophylline, isobutylmethylxanthine, quinidine, and compound Ro 20-1724 (4-(3-butoxyl-4-methoxybenzyl)-2-imidazolidinone) elicited very marked increases in serotonin acetyltransferase activity in glands cultured in the dark. Levels of activity attained after 6 h in culture approached or exceeded the maximum levels attained at middark phase of the diurnal cycle in vivo. Effects of theophylline and compound Ro 20-1724 were additive. Supplements of dibutryl cAMP had little or no effect upon levels of serotonin acetyltransferase activity when tested alone or in combination with theophylline but further enhanced the increase in the level of enzyme activity elicited by Ro 20-1724. Adenosine and cAMP had little or no effect upon levels of serotonin acetyltransferase activity. It is concluded that levels of serotonin acetyltransferase activity in the chick pineal gland are regulated by a repressive, negative-control mechanism, which probably involves a membranous adenosine receptor."}
{"id": "PMID:210907", "title": "Temperature-induced changes of spin-labelled radioactive lipids in isolated guinea pig liver microsomal membranes before and in mitochondrial membranes after their translocation.", "content": "Lipids of isolated guinea pig liver microsomal membranes were labelled biosynthetically with isomeric doxyl stearic acid and temperature-induced changes of these membranes were studied by electron spin resonance. A noticeable discontinuity was detected at 10--12 degree C with 12- or 16-doxyl stearic acid containing membrane lipids which was attributed to the spin-labelled lipid--microsomal membrane protein interactions since no such discontinuity was detected in liposomes prepared from total lipid extracts of microsomal membranes. When microsomal membranes containing radioactive isomeric spin-labelled lipids were incubated with unlabelled mitochondria, reisolated mitochondrial membranes contained translocated radioactive isomeric spin-labelled lipids. Temperature-induced changes in these membranes showed no discontinuity with either isomeric doxyl stearic acid derivative, establishing a difference in the environment of translocated lipids in the membrane donor compared with that in the membrane acceptor. Microsomal membranes recovered from translocation experiments showed the same behaviour as the original membranes and exhibited the same discontinuity at 10--12 degree C, establishing that the translocation incubation itself did not alter the spin-labelled lipid interaction within these membranes. Studies of the loss of paramagnetism of spin-labelled lipids in microsomal membranes before and in mitochondrial membranes after their translocation showed a significant difference and suggested that both the outer and the inner mitochondrial membranes might have been involved.", "contents": "Temperature-induced changes of spin-labelled radioactive lipids in isolated guinea pig liver microsomal membranes before and in mitochondrial membranes after their translocation. Lipids of isolated guinea pig liver microsomal membranes were labelled biosynthetically with isomeric doxyl stearic acid and temperature-induced changes of these membranes were studied by electron spin resonance. A noticeable discontinuity was detected at 10--12 degree C with 12- or 16-doxyl stearic acid containing membrane lipids which was attributed to the spin-labelled lipid--microsomal membrane protein interactions since no such discontinuity was detected in liposomes prepared from total lipid extracts of microsomal membranes. When microsomal membranes containing radioactive isomeric spin-labelled lipids were incubated with unlabelled mitochondria, reisolated mitochondrial membranes contained translocated radioactive isomeric spin-labelled lipids. Temperature-induced changes in these membranes showed no discontinuity with either isomeric doxyl stearic acid derivative, establishing a difference in the environment of translocated lipids in the membrane donor compared with that in the membrane acceptor. Microsomal membranes recovered from translocation experiments showed the same behaviour as the original membranes and exhibited the same discontinuity at 10--12 degree C, establishing that the translocation incubation itself did not alter the spin-labelled lipid interaction within these membranes. Studies of the loss of paramagnetism of spin-labelled lipids in microsomal membranes before and in mitochondrial membranes after their translocation showed a significant difference and suggested that both the outer and the inner mitochondrial membranes might have been involved."}
{"id": "PMID:210908", "title": "Mechanism of heparin and serum lipoprotein interaction: effects of calcium, phosphorylcholine, and a serum fraction.", "content": "The mechanism of formation of an insoluble complex between heparin and rat serum lipoprotein has been studied. Optical density changes during the reaction, counting of the fatty acid labelled lipoproteins in the precipitates, and complexing of [14C]palmitate-labelled lipoprotein with heparin-CNBr-Sepharose were used to quantitatively determine the formation of insoluble complexes. The maximal heparin--lipoprotein complex formation requires 25--30 mM of Ca2+, but with micromolar amounts of phosphorylcholine, the reaction was saturated at only 10 mM of Ca2+. The effect of phosphorylcholine in promoting the reaction was lost when purified chylomicrons or very low density lipoproteins were used. The effect of phosphorylcholine in promoting the interaction between heparin and pure chylomicrons or very low density lipoproteins was regained when a crude serum protein factor of unwashed chylomicrons was added to the system, suggesting that rat serum contains a protein factor(s) which normally inhibits the heparin--lipoprotein interaction by raising the requirement of Ca2+. Phosphorylcholine counteracted the effect of this protein, thereby favouring the precipitation reaction in the presence of much lower concentration of Ca2+. The results have been discussed with special reference to the possibility of a relationship between mucopolysaccharides, Ca2+, lipoproteins, and arterial phospholipids in the pathogenesis of atherosclerosis.", "contents": "Mechanism of heparin and serum lipoprotein interaction: effects of calcium, phosphorylcholine, and a serum fraction. The mechanism of formation of an insoluble complex between heparin and rat serum lipoprotein has been studied. Optical density changes during the reaction, counting of the fatty acid labelled lipoproteins in the precipitates, and complexing of [14C]palmitate-labelled lipoprotein with heparin-CNBr-Sepharose were used to quantitatively determine the formation of insoluble complexes. The maximal heparin--lipoprotein complex formation requires 25--30 mM of Ca2+, but with micromolar amounts of phosphorylcholine, the reaction was saturated at only 10 mM of Ca2+. The effect of phosphorylcholine in promoting the reaction was lost when purified chylomicrons or very low density lipoproteins were used. The effect of phosphorylcholine in promoting the interaction between heparin and pure chylomicrons or very low density lipoproteins was regained when a crude serum protein factor of unwashed chylomicrons was added to the system, suggesting that rat serum contains a protein factor(s) which normally inhibits the heparin--lipoprotein interaction by raising the requirement of Ca2+. Phosphorylcholine counteracted the effect of this protein, thereby favouring the precipitation reaction in the presence of much lower concentration of Ca2+. The results have been discussed with special reference to the possibility of a relationship between mucopolysaccharides, Ca2+, lipoproteins, and arterial phospholipids in the pathogenesis of atherosclerosis."}
{"id": "PMID:210909", "title": "A direct radioimmunoassay for tonin.", "content": "A sensitive radioimmunoassay for the measurement of tonin is described. It is based on the use of antibodies produced in rabbits against highly purified tonin obtained from rat submaxillary gland. A radioiodinated enzyme with high specific activity was obtained by the chloramine-T method. Optimal conditions for radioimmunoprecipitation were established and the double-antibody method was used to separate bound and free tonin. The radioimmunoassay may be used to measure tonin in amounts as low as 150 pg. This radioimmunoassay was applied to the measurement of tonin in rat saliva and in homogenates of submaxillary glands. Excellent correlation was found between tonin activity measured fluorometrically and tonin concentration obtained by the radioimmunoassay.", "contents": "A direct radioimmunoassay for tonin. A sensitive radioimmunoassay for the measurement of tonin is described. It is based on the use of antibodies produced in rabbits against highly purified tonin obtained from rat submaxillary gland. A radioiodinated enzyme with high specific activity was obtained by the chloramine-T method. Optimal conditions for radioimmunoprecipitation were established and the double-antibody method was used to separate bound and free tonin. The radioimmunoassay may be used to measure tonin in amounts as low as 150 pg. This radioimmunoassay was applied to the measurement of tonin in rat saliva and in homogenates of submaxillary glands. Excellent correlation was found between tonin activity measured fluorometrically and tonin concentration obtained by the radioimmunoassay."}
{"id": "PMID:210910", "title": "Flow kinetics of lactate dehydrogenase chemically attached to nylon tubing.", "content": "Rabbit muscle lactate dehydrogenase (EC 1.1.1.27) was attached covalently to the inner surface of nylon tubing; a modified technique, involving benzidine and glutaraldehyde, was used, and the resulting immobilized enzyme showed no loss of activity over a period of several months. An experimental study was made of the flow kinetics for the reaction between pyruvate and reduced nicotinamide adenine dinucleotide in two limiting cases, one substrate in excess and the concentration of the other one varied. A range of flow rates and temperatures was covered. The results were analyzed in various ways on the basis of the Kobayashi--Laidler treatment of flow systems. It was concluded that the kinetics are largely diffusion-controlled, especially at the lower substrate concentrations and flow rates. The values of the apparent Michaelis constants vary with flow rate vf, being linear in vf-1/3, and the values extrapolated to infinite flow rate (vf-1/3 = 0) approach the values for the enzyme in free solution. Analysis of the rates led to activation energies for the diffusion of the two substrates.", "contents": "Flow kinetics of lactate dehydrogenase chemically attached to nylon tubing. Rabbit muscle lactate dehydrogenase (EC 1.1.1.27) was attached covalently to the inner surface of nylon tubing; a modified technique, involving benzidine and glutaraldehyde, was used, and the resulting immobilized enzyme showed no loss of activity over a period of several months. An experimental study was made of the flow kinetics for the reaction between pyruvate and reduced nicotinamide adenine dinucleotide in two limiting cases, one substrate in excess and the concentration of the other one varied. A range of flow rates and temperatures was covered. The results were analyzed in various ways on the basis of the Kobayashi--Laidler treatment of flow systems. It was concluded that the kinetics are largely diffusion-controlled, especially at the lower substrate concentrations and flow rates. The values of the apparent Michaelis constants vary with flow rate vf, being linear in vf-1/3, and the values extrapolated to infinite flow rate (vf-1/3 = 0) approach the values for the enzyme in free solution. Analysis of the rates led to activation energies for the diffusion of the two substrates."}
{"id": "PMID:210911", "title": "Probes of the structure of phosphoenolpyruvate synthetase: effects of a transition state analogue on enzyme conformation.", "content": "Phosphoenolpyruvate synthetase of Escherichia coli is strongly inhibited by oxalate. The magnitude of the inhibition constant for oxalate suggests that this compound acts to produce a transition state analogue, in keeping with the suggestion of others that oxalate mimics the structure of enolpyruvate, a presumed catalytic intermediate in the enzymatic reaction. The addition of oxalate together with ATP results in a dramatic shielding of sensitive amino acid residues from reaction with both N-ethyl maleimide and phenylglyoxal. Thus, under conditions otherwise giving rise to almost complete inactivation by either reagent, no loss of activity is detectable in the presence of oxalate and ATP. These results indicate the formation of an enclosed structure during catalysis in which reactive groups are rendered quite inaccessible to solvent.", "contents": "Probes of the structure of phosphoenolpyruvate synthetase: effects of a transition state analogue on enzyme conformation. Phosphoenolpyruvate synthetase of Escherichia coli is strongly inhibited by oxalate. The magnitude of the inhibition constant for oxalate suggests that this compound acts to produce a transition state analogue, in keeping with the suggestion of others that oxalate mimics the structure of enolpyruvate, a presumed catalytic intermediate in the enzymatic reaction. The addition of oxalate together with ATP results in a dramatic shielding of sensitive amino acid residues from reaction with both N-ethyl maleimide and phenylglyoxal. Thus, under conditions otherwise giving rise to almost complete inactivation by either reagent, no loss of activity is detectable in the presence of oxalate and ATP. These results indicate the formation of an enclosed structure during catalysis in which reactive groups are rendered quite inaccessible to solvent."}
{"id": "PMID:210912", "title": "Pneumonia in calves produced with aerosols of bovine herpesvirus 1 and Pasteurella haemolytica.", "content": "In each of 11 experiments, four calves were exposed first to an aerosol of bovine herpesvirus 1 (BHV1, virus of infectious bovine rhinotracheitis) and second to an aerosol of Pasteurella haemolytica. The interval between aerosols was three to five days. In two other experiments, calves were exposed only to a bacterial aerosol. Climate was controlled for all experiments from the day of viral exposure and for eight of the experiments it was also controlled for four to six days before the first aerosol. The concentration of infectious doses of virus in the aerosols and the number of bacteria in the aerosols of each calf were determined. Macroscopically recognizable rhinitis, tonsillitis, laryngitis, tracheitis and pneumonia of lobar distribution in 42 lobes from 11 calves were seen in five experiments in which bacterial aerosol followed the viral aerosol by at least four days. One calf died with marked respiratory disease in each of four experiments within four days of exposure to the bacterial aerosol. Production of pneumonia was dependent on an interval between aerosols of at least four days but not on the condition of controlled climate on the environmental chamber either before or after the viral aerosol nor on the period of habituation allowed calves of some experiments.", "contents": "Pneumonia in calves produced with aerosols of bovine herpesvirus 1 and Pasteurella haemolytica. In each of 11 experiments, four calves were exposed first to an aerosol of bovine herpesvirus 1 (BHV1, virus of infectious bovine rhinotracheitis) and second to an aerosol of Pasteurella haemolytica. The interval between aerosols was three to five days. In two other experiments, calves were exposed only to a bacterial aerosol. Climate was controlled for all experiments from the day of viral exposure and for eight of the experiments it was also controlled for four to six days before the first aerosol. The concentration of infectious doses of virus in the aerosols and the number of bacteria in the aerosols of each calf were determined. Macroscopically recognizable rhinitis, tonsillitis, laryngitis, tracheitis and pneumonia of lobar distribution in 42 lobes from 11 calves were seen in five experiments in which bacterial aerosol followed the viral aerosol by at least four days. One calf died with marked respiratory disease in each of four experiments within four days of exposure to the bacterial aerosol. Production of pneumonia was dependent on an interval between aerosols of at least four days but not on the condition of controlled climate on the environmental chamber either before or after the viral aerosol nor on the period of habituation allowed calves of some experiments."}
{"id": "PMID:210913", "title": "The effect of cholera toxin and heat labile and heat stable Escherichia coli enterotoxin on cyclic AMP concentrations in small intestinal mucosa of pig and rabbit.", "content": "The effect of cholera toxin, heat labile and heat stable Escherichia coli enterotoxin on mucosal cyclic AMP concentrations was determined on the proximal jejunum of weanling pigs and young rabbits. Ligated loops were injected with solutions containing no enterotoxin for control and either cholera toxin, heat labile or heat stable E. coli enterotoxin. The loops were drained after either two, four or six hours incubation at which time accumulated fluid was recorded and mucosal samples removed for determination of cyclic AMP concentration. In the rabbit, cholera toxin and heat labile, but not heat stable E. coli enterotoxin stimulated intestinal secretion while in the pig all three enterotoxins induced net fluid accumulation. Cholera toxin and heat labile, but not heat stable E. coli enterotoxin elevated rabbit mucosal cyclic AMP concentrations. In the pig these enterotoxins had no significant effect on mucosal cyclic AMP concentrations. The results are inconsistent with the hypothesis that the adenyl cyclase system is an essential step for enterotoxin induced intestinal secretion. The activation of intestinal adenyl cyclase by bacterial enterotoxins may only be an associated and not a necessary event for the stimulation of intestinal secretion.", "contents": "The effect of cholera toxin and heat labile and heat stable Escherichia coli enterotoxin on cyclic AMP concentrations in small intestinal mucosa of pig and rabbit. The effect of cholera toxin, heat labile and heat stable Escherichia coli enterotoxin on mucosal cyclic AMP concentrations was determined on the proximal jejunum of weanling pigs and young rabbits. Ligated loops were injected with solutions containing no enterotoxin for control and either cholera toxin, heat labile or heat stable E. coli enterotoxin. The loops were drained after either two, four or six hours incubation at which time accumulated fluid was recorded and mucosal samples removed for determination of cyclic AMP concentration. In the rabbit, cholera toxin and heat labile, but not heat stable E. coli enterotoxin stimulated intestinal secretion while in the pig all three enterotoxins induced net fluid accumulation. Cholera toxin and heat labile, but not heat stable E. coli enterotoxin elevated rabbit mucosal cyclic AMP concentrations. In the pig these enterotoxins had no significant effect on mucosal cyclic AMP concentrations. The results are inconsistent with the hypothesis that the adenyl cyclase system is an essential step for enterotoxin induced intestinal secretion. The activation of intestinal adenyl cyclase by bacterial enterotoxins may only be an associated and not a necessary event for the stimulation of intestinal secretion."}
{"id": "PMID:210914", "title": "Enterotoxigenic Clostridium perfringens type A isolated from intestinal contents of cattle, sheep and chickens.", "content": "One hundred and fourteen strains of Clostridium perfringens, isolated from the intestinal contents of cattle, sheep, and chickens with enteritis or other disease conditions were studied for their ability to produce enterotoxin. Reversed passive hemagglutination, fluorescent antibody and immunodiffusion tests were used. On the basis of the reversed passive hemagglutination titres, supported by the other two tests, enterotoxigenicity of the strains was arbitrarily classified into two categories: highly enterotoxigenic and potentially enterotoxigenic, with 12% falling into each category. All the highly enterotoxigenic strains originated from cases of enteritis and included all three animal species. Apart from enterotoxigenicity, one C. perfringens strain produced beta toxin (type C) and 21 strains produced large amounts of alpha-toxin. The latter strains were predominantly associated with necrotic enteritis in chickens.", "contents": "Enterotoxigenic Clostridium perfringens type A isolated from intestinal contents of cattle, sheep and chickens. One hundred and fourteen strains of Clostridium perfringens, isolated from the intestinal contents of cattle, sheep, and chickens with enteritis or other disease conditions were studied for their ability to produce enterotoxin. Reversed passive hemagglutination, fluorescent antibody and immunodiffusion tests were used. On the basis of the reversed passive hemagglutination titres, supported by the other two tests, enterotoxigenicity of the strains was arbitrarily classified into two categories: highly enterotoxigenic and potentially enterotoxigenic, with 12% falling into each category. All the highly enterotoxigenic strains originated from cases of enteritis and included all three animal species. Apart from enterotoxigenicity, one C. perfringens strain produced beta toxin (type C) and 21 strains produced large amounts of alpha-toxin. The latter strains were predominantly associated with necrotic enteritis in chickens."}
{"id": "PMID:210915", "title": "Opiate properties of SKF 525A.", "content": "SKF 525A, a classical inhibitor of microsomal drug-metabolizing enzymes, is structurally similar to the diphenylpropylamine analgesics, and certain reported effects in animals resemble those produced by opiate drugs. In an opiate radioreceptor assay, SKF 525A was 50 times less potent than methadone in the absence of sodium and 10 times less potent in the prescence of sodium. The nature of the sodium effect indicates SKF 525A to have less opiate agonist character than does methadone. In mice, 2 mg of SKF 525A given intraperitoneally induced less profound analgesia on a hot plate (44 degrees C) than did 0.1 mg of methadone. Analgesia by SKF 525A was prevented by pretreatment of the mice with naloxone. In rats, 50 microgram of SKF 525A given intracerebroventricularly was analgesic.", "contents": "Opiate properties of SKF 525A. SKF 525A, a classical inhibitor of microsomal drug-metabolizing enzymes, is structurally similar to the diphenylpropylamine analgesics, and certain reported effects in animals resemble those produced by opiate drugs. In an opiate radioreceptor assay, SKF 525A was 50 times less potent than methadone in the absence of sodium and 10 times less potent in the prescence of sodium. The nature of the sodium effect indicates SKF 525A to have less opiate agonist character than does methadone. In mice, 2 mg of SKF 525A given intraperitoneally induced less profound analgesia on a hot plate (44 degrees C) than did 0.1 mg of methadone. Analgesia by SKF 525A was prevented by pretreatment of the mice with naloxone. In rats, 50 microgram of SKF 525A given intracerebroventricularly was analgesic."}
{"id": "PMID:210916", "title": "Effect of different drugs on a cytochrome c--phospholipid bilayer membrane.", "content": "Liposomes were prepared from dipalmitoyl phosphatidylcholine and dicetylphosphate and their interaction with the extrinsic membrane protein cytochrome c examined in terms of changes in 22Na permeability, electrophoretic mobility, protein binding, and motion of an incorporated spin label. The amount of cytochrome c bound displays no significant temperature dependence over the temperature range studied (from 30 to 55 degrees C) whereas cytochrome c causes an increase in 22Na efflux only above the phospholipid phase transition temperature. Interaction of the protein with the lipid vesicles causes no significant disturbance in the bilayer interior as monitored by the motion of the incorporated spin probe. The drugs 2,4-dinitrophenol and ethacrynic acid, both of which increase the magnitude of the vesicle negative charge, enhance both cytochrome c binding and its effect on 22Na permeability. In contrast, the local anesthetic dibucaine, which induces a positive surface charge on these liposomes, reduces both protein binding and the protein-induced increase in 22Na efflux. Finally, the chemicals butylated hydroxytoluene, 2-tert-butylphenol, and tert-butylbenzene, all of which cause early 'melting' of the phospholipid fatty acyl chains, block the capacity of cytochrome c to enhance 22Na permeability while having no effect on its binding to the vesicles.", "contents": "Effect of different drugs on a cytochrome c--phospholipid bilayer membrane. Liposomes were prepared from dipalmitoyl phosphatidylcholine and dicetylphosphate and their interaction with the extrinsic membrane protein cytochrome c examined in terms of changes in 22Na permeability, electrophoretic mobility, protein binding, and motion of an incorporated spin label. The amount of cytochrome c bound displays no significant temperature dependence over the temperature range studied (from 30 to 55 degrees C) whereas cytochrome c causes an increase in 22Na efflux only above the phospholipid phase transition temperature. Interaction of the protein with the lipid vesicles causes no significant disturbance in the bilayer interior as monitored by the motion of the incorporated spin probe. The drugs 2,4-dinitrophenol and ethacrynic acid, both of which increase the magnitude of the vesicle negative charge, enhance both cytochrome c binding and its effect on 22Na permeability. In contrast, the local anesthetic dibucaine, which induces a positive surface charge on these liposomes, reduces both protein binding and the protein-induced increase in 22Na efflux. Finally, the chemicals butylated hydroxytoluene, 2-tert-butylphenol, and tert-butylbenzene, all of which cause early 'melting' of the phospholipid fatty acyl chains, block the capacity of cytochrome c to enhance 22Na permeability while having no effect on its binding to the vesicles."}
{"id": "PMID:210918", "title": "Viruses in sewage: effect of phosphate removal with calcium hydroxide (lime).", "content": "During calcium hydroxide (lime) treatment (pH 9.6 to 10.5) of wastewaters for phosphate removal there was also a two-log removal of added poliovirus (type I, Sabin) from effluents. A similar virus reduction was seen in the sludge generated in these experiments. However, in view of the limitations of techniques for virus recovery from sludge, only a small portion of the infectious virus present in lime sludge may have been detected. Storage of lime sludge at 28 degrees C for up to 48 h produced no appreciable reduction in the virus titre. Five sets of field samples of sewage, effluents, and sludge from a sewage treatment plant (Kemptville, Ont.) which utilizes lime for phosphate removal were also examined for indigenous viruses being BS-C-1 cells. All of the sample of lime sludge and 80% of the samples of both sewage and lime-treated effluent revealed virus; after chlorination only 20% of the lime-treated effluent samples were positive for virus. In contrast, in an earlier study with essentially the same experimental set up, 76% of the sample of chlorinated primary effluent were found to contain virus. Because of the easily detectable quantities of infectious virus in lime sludge and due to the lack of virus inactivation during storage of such sludge, caution must be exercised in its handling and disposal.", "contents": "Viruses in sewage: effect of phosphate removal with calcium hydroxide (lime). During calcium hydroxide (lime) treatment (pH 9.6 to 10.5) of wastewaters for phosphate removal there was also a two-log removal of added poliovirus (type I, Sabin) from effluents. A similar virus reduction was seen in the sludge generated in these experiments. However, in view of the limitations of techniques for virus recovery from sludge, only a small portion of the infectious virus present in lime sludge may have been detected. Storage of lime sludge at 28 degrees C for up to 48 h produced no appreciable reduction in the virus titre. Five sets of field samples of sewage, effluents, and sludge from a sewage treatment plant (Kemptville, Ont.) which utilizes lime for phosphate removal were also examined for indigenous viruses being BS-C-1 cells. All of the sample of lime sludge and 80% of the samples of both sewage and lime-treated effluent revealed virus; after chlorination only 20% of the lime-treated effluent samples were positive for virus. In contrast, in an earlier study with essentially the same experimental set up, 76% of the sample of chlorinated primary effluent were found to contain virus. Because of the easily detectable quantities of infectious virus in lime sludge and due to the lack of virus inactivation during storage of such sludge, caution must be exercised in its handling and disposal."}
{"id": "PMID:210919", "title": "Intracellular cyclic adenosine 3',5'-monophosphate levels and streptomycin production in cultures of Streptomyces griseus.", "content": "Changes in the amount of cyclic 3',5'-adenosine monophosphate within the mycelium of Streptomyces griseus were measured as cultures progressed through trophophase and idiophase in a complex medium supporting growth and streptomycin synthesis. Concentrations were highest before the cultures entered stationary phase and had declined 90% by 5 h before the antibiotic was produced. This low conentration was maintained while the antibiotic accumulated during the idiophase. The results indicate that the onset of streptomycin synthesis is not directly mediated by an increase in intracellular cyclic 3',5'-adenosine monophosphate concentration, and thus that antibiotic production in S. griseus is not controlled by catabolite repression.", "contents": "Intracellular cyclic adenosine 3',5'-monophosphate levels and streptomycin production in cultures of Streptomyces griseus. Changes in the amount of cyclic 3',5'-adenosine monophosphate within the mycelium of Streptomyces griseus were measured as cultures progressed through trophophase and idiophase in a complex medium supporting growth and streptomycin synthesis. Concentrations were highest before the cultures entered stationary phase and had declined 90% by 5 h before the antibiotic was produced. This low conentration was maintained while the antibiotic accumulated during the idiophase. The results indicate that the onset of streptomycin synthesis is not directly mediated by an increase in intracellular cyclic 3',5'-adenosine monophosphate concentration, and thus that antibiotic production in S. griseus is not controlled by catabolite repression."}
{"id": "PMID:210920", "title": "Musculoskeletal deformities following treatment of Wilms' tumour.", "content": "Wilms' tumour is one of the most common neoplasms of infancy and childhood. Current treatment regimens result in a cure rate of about 80% for localized tumours but may also cause musculoskeletal deformities. Assessment of 21 patients previously treated for Wilms' tumour showed that all had flank atrophy on the treated side. Radiologic abnormalities included asymmetry of vertebral bodies, vertebral end-plate irregularities, scoliosis,  kyphosis, platyspondyly and hypoplasia of the ilium. Although the vertebral changes following radiotherapy for Wilms' tumour are present from an early age and the potential is great for an increase in spinal deformity with growth, few spinal curves progress past 20 degree. Since one cannot predict which curves will progress, all such patients need careful orthopedic follow-up until skeletal maturity is achieved.", "contents": "Musculoskeletal deformities following treatment of Wilms' tumour. Wilms' tumour is one of the most common neoplasms of infancy and childhood. Current treatment regimens result in a cure rate of about 80% for localized tumours but may also cause musculoskeletal deformities. Assessment of 21 patients previously treated for Wilms' tumour showed that all had flank atrophy on the treated side. Radiologic abnormalities included asymmetry of vertebral bodies, vertebral end-plate irregularities, scoliosis,  kyphosis, platyspondyly and hypoplasia of the ilium. Although the vertebral changes following radiotherapy for Wilms' tumour are present from an early age and the potential is great for an increase in spinal deformity with growth, few spinal curves progress past 20 degree. Since one cannot predict which curves will progress, all such patients need careful orthopedic follow-up until skeletal maturity is achieved."}
{"id": "PMID:210924", "title": "Hamster embryo cells transformed by herpes simplex virus: reactions with adeno-associated satellite virus (AAV) and its adenovirus helpers.", "content": "We have studied the reactions of hamster embryo cells transformed by ultraviolet-inactivated herpes simplex type 2 (333-8-9 T cells) to infections with adeno-associated satellite virus (AAV) and its adenovirus helpers. Resident HSV structural antigens were not detectable in early or late passage of 333-8-9 T cells. AAV structural antigens were not detected in these cells unless the cells were coinfected with a helper adenovirus. In early passage 333-8-9 T cells were permissive to infections with simian adenovirus SV15 whereas normal hamster cell line LSH was nonpermissive. In some late passages of 333-8-9 T cells infections with SV15 adenovirus led to the production of viruslike particles whose morphology was identical with reoviruses.", "contents": "Hamster embryo cells transformed by herpes simplex virus: reactions with adeno-associated satellite virus (AAV) and its adenovirus helpers. We have studied the reactions of hamster embryo cells transformed by ultraviolet-inactivated herpes simplex type 2 (333-8-9 T cells) to infections with adeno-associated satellite virus (AAV) and its adenovirus helpers. Resident HSV structural antigens were not detectable in early or late passage of 333-8-9 T cells. AAV structural antigens were not detected in these cells unless the cells were coinfected with a helper adenovirus. In early passage 333-8-9 T cells were permissive to infections with simian adenovirus SV15 whereas normal hamster cell line LSH was nonpermissive. In some late passages of 333-8-9 T cells infections with SV15 adenovirus led to the production of viruslike particles whose morphology was identical with reoviruses."}
{"id": "PMID:210925", "title": "Multiple nuclear protein kinase activities in rat liver and hepatoma 3924A.", "content": "Multiple protein kinase activities were isolated from nuclei of rat and hepatoma 3924A, and purified 40- to 140-fold, respectively. Hepatic protein kinase-I exhibited high activity with casein as substrate, but was relatively inactive with either liver and hepatoma chromatin or mixed histone. In contrast, hepatoma protein kinase-I showed equivalent activity with casein and liver chromatin. Protein kinase-IIA, -IIB and-IIC from both tissues were more active with liver chromatin in comparison to casein and hepatoma chromatin, and exhibited similar electrophoretic profiles of 32P-chromatin.", "contents": "Multiple nuclear protein kinase activities in rat liver and hepatoma 3924A. Multiple protein kinase activities were isolated from nuclei of rat and hepatoma 3924A, and purified 40- to 140-fold, respectively. Hepatic protein kinase-I exhibited high activity with casein as substrate, but was relatively inactive with either liver and hepatoma chromatin or mixed histone. In contrast, hepatoma protein kinase-I showed equivalent activity with casein and liver chromatin. Protein kinase-IIA, -IIB and-IIC from both tissues were more active with liver chromatin in comparison to casein and hepatoma chromatin, and exhibited similar electrophoretic profiles of 32P-chromatin."}
{"id": "PMID:210926", "title": "Development of biliary and hepatic neoplasms in guinea pigs treated with N-nitrosobis(2-oxopropyl)amine.", "content": "N-Nitrosobis(2-oxopropyl)amine (BOP) was administered subcutaneously to 29 male inbred strain 13 guinea pigs at weekly intervals for 4 weeks. The guinea pigs were observed until their death or termination of the experiment at the end of 55 weeks. Of 14 guinea pigs that survived more than 30 weeks, 7 animals developed cholangiocarcinomas and 2 developed hepatocellular carcinomas. Tumors of other sites were not found.", "contents": "Development of biliary and hepatic neoplasms in guinea pigs treated with N-nitrosobis(2-oxopropyl)amine. N-Nitrosobis(2-oxopropyl)amine (BOP) was administered subcutaneously to 29 male inbred strain 13 guinea pigs at weekly intervals for 4 weeks. The guinea pigs were observed until their death or termination of the experiment at the end of 55 weeks. Of 14 guinea pigs that survived more than 30 weeks, 7 animals developed cholangiocarcinomas and 2 developed hepatocellular carcinomas. Tumors of other sites were not found."}
{"id": "PMID:210927", "title": "Base specificity in the binding of benzo[a]pyrene diol epoxide to simian virus 40 DNA.", "content": "[14C]Simian virus 40 (SV40) DNA was reacted with [3H]7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene to give 0.60 adducts per genome. The modified DNA was digested to completion with Hind III restriction endonuclease and the 6 fragments isolated by polyacrylamide gel electrophoresis. Hydrocarbon binding to the fragments was proportional to their guanine--cytosine (G--C) content, reflecting selective reaction of the hydrocarbon with deoxyguanosine residues. No sites unusually susceptible to alkylation were detected.", "contents": "Base specificity in the binding of benzo[a]pyrene diol epoxide to simian virus 40 DNA. [14C]Simian virus 40 (SV40) DNA was reacted with [3H]7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene to give 0.60 adducts per genome. The modified DNA was digested to completion with Hind III restriction endonuclease and the 6 fragments isolated by polyacrylamide gel electrophoresis. Hydrocarbon binding to the fragments was proportional to their guanine--cytosine (G--C) content, reflecting selective reaction of the hydrocarbon with deoxyguanosine residues. No sites unusually susceptible to alkylation were detected."}
{"id": "PMID:210928", "title": "Carcinogenesis of nitrosomethylundecylamine in Fischer rats.", "content": "Nitrosomethylundecylamine was synthesized and administered to Fischer rats by gavage in olive oil solution, at a dose of 46 mg/animal/week for 30 weeks. There were high incidences of hepatocellular carcinomas and cholangiocarcinomas in the liver and of squamous cell carcinomas and alveolar cell adenocarcinomas in the lung. In contrast with the activity of the next higher homolog, nitrosomethyldodecylamine, no bladder tumors were induced.", "contents": "Carcinogenesis of nitrosomethylundecylamine in Fischer rats. Nitrosomethylundecylamine was synthesized and administered to Fischer rats by gavage in olive oil solution, at a dose of 46 mg/animal/week for 30 weeks. There were high incidences of hepatocellular carcinomas and cholangiocarcinomas in the liver and of squamous cell carcinomas and alveolar cell adenocarcinomas in the lung. In contrast with the activity of the next higher homolog, nitrosomethyldodecylamine, no bladder tumors were induced."}
{"id": "PMID:210929", "title": "Antagonistic action between cyclic AMP and estrogen in phosphorylation of mammary tumor nuclear proteins.", "content": "A new protein kinase-dependent phosphorylation occurs in the nuclei of hormone-dependent, 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced mammary carcinoma following preincubation of tumor slices with cyclic adenosine 3',5'-monophosphate (cAMP). The presence of 17beta-estradiol in the medium inhibits this effect. Both events have been observed in vivo in the nuclei of DMBA-induced tumors. The phosphorylation pattern of nuclei in hormone-independent mammary tumor, DMBA No. 1, however, is not affected by preincubation with either cAMP or estrogen. These findings suggest that the antagonistic effect of cAMP and estrogen in the growth control of mammary tumors is exerted through a specific action on nuclear protein phosphorylation and that these events correlate with the hormone-dependency of the tumors.", "contents": "Antagonistic action between cyclic AMP and estrogen in phosphorylation of mammary tumor nuclear proteins. A new protein kinase-dependent phosphorylation occurs in the nuclei of hormone-dependent, 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced mammary carcinoma following preincubation of tumor slices with cyclic adenosine 3',5'-monophosphate (cAMP). The presence of 17beta-estradiol in the medium inhibits this effect. Both events have been observed in vivo in the nuclei of DMBA-induced tumors. The phosphorylation pattern of nuclei in hormone-independent mammary tumor, DMBA No. 1, however, is not affected by preincubation with either cAMP or estrogen. These findings suggest that the antagonistic effect of cAMP and estrogen in the growth control of mammary tumors is exerted through a specific action on nuclear protein phosphorylation and that these events correlate with the hormone-dependency of the tumors."}
{"id": "PMID:210930", "title": "Heterogeneity of tumor cells from a single mouse mammary tumor.", "content": "By the use of a variety of cell culture and separation methods, four cell lines were isolated from a single autochthonous BALB/cfC3H mammary tumor. These lines differ markedly from each other in culture morphology, various in vitro growth properties, expression of murine mammary tumor virus antigen, and karyotype, yet all four lines are tumorigenic in normal, syngeneic hosts, yielding tumors of generally similar histology, although distinct from the original neoplasm. Three of the four lines have been cloned from soft agar. The clones exhibit the same growth properties as the lines from which they were derived. Karyotypic analysis of the parent tumor revealed the presence of cells with heterogeneous numbers of chromosomes similar to those seen in the isolated lines, suggesting both the presence of these distinct cell types in the original neoplasm and a genetic origin of the diversity.", "contents": "Heterogeneity of tumor cells from a single mouse mammary tumor. By the use of a variety of cell culture and separation methods, four cell lines were isolated from a single autochthonous BALB/cfC3H mammary tumor. These lines differ markedly from each other in culture morphology, various in vitro growth properties, expression of murine mammary tumor virus antigen, and karyotype, yet all four lines are tumorigenic in normal, syngeneic hosts, yielding tumors of generally similar histology, although distinct from the original neoplasm. Three of the four lines have been cloned from soft agar. The clones exhibit the same growth properties as the lines from which they were derived. Karyotypic analysis of the parent tumor revealed the presence of cells with heterogeneous numbers of chromosomes similar to those seen in the isolated lines, suggesting both the presence of these distinct cell types in the original neoplasm and a genetic origin of the diversity."}
{"id": "PMID:210931", "title": "Acute and long-term cytogenetic effects of childhood cancer chemotherapy and radiotherapy.", "content": "Approximately 30 banded karyotypes per subject from the lymphocytes of 66 childhood cancer patients and 14 noncancer control subjects have been analyzed in an attempt to gauge the late effects of anticancer chemotherapy and chemotherapy plus radiotherapy on the genetic material, i.e., the chromosomes. The frequencies (f) of aberrant cells were: f = 1/306 among cells from noncancer controls; f = 1/377 from cancer patients prior to therapy, f = 1/15 from patients currently on chemotherapy; and f = 1/32 from posttherapy patients (range, 3 months to 22 years poattherapy). The frequency of chromosomally aberrant cells did not appear to change with time among posttherapy patients, and the majority of aberrations detected in subjects from this group were balanced rearrangements. This was not the case for the on-therapy group where unbalanced rearrangements and unstable aberrations predominated.", "contents": "Acute and long-term cytogenetic effects of childhood cancer chemotherapy and radiotherapy. Approximately 30 banded karyotypes per subject from the lymphocytes of 66 childhood cancer patients and 14 noncancer control subjects have been analyzed in an attempt to gauge the late effects of anticancer chemotherapy and chemotherapy plus radiotherapy on the genetic material, i.e., the chromosomes. The frequencies (f) of aberrant cells were: f = 1/306 among cells from noncancer controls; f = 1/377 from cancer patients prior to therapy, f = 1/15 from patients currently on chemotherapy; and f = 1/32 from posttherapy patients (range, 3 months to 22 years poattherapy). The frequency of chromosomally aberrant cells did not appear to change with time among posttherapy patients, and the majority of aberrations detected in subjects from this group were balanced rearrangements. This was not the case for the on-therapy group where unbalanced rearrangements and unstable aberrations predominated."}
{"id": "PMID:210934", "title": "Spontaneous esophageal carcinoma and epithelial cell line of an adult rhesus monkey.", "content": "A continuous epithelial cell line, 816A, was established from a lymph node of an adult rhesus monkey with metastatic esophageal carcinoma. These cells are characterized by the presence of desmosomes and a markedly heteroploid karyotype. At a relatively early culture age, electron microscopy showed both budding and extracellular type C virus. Antigen reactive with antisera to Mason-Pfizer monkey virus was observed by complement-fixation. The level of this antigen decreased with increased culture age. To our knowledge, the 816A cells represent the only established simian or human cell line of esophageal carcinoma origin.", "contents": "Spontaneous esophageal carcinoma and epithelial cell line of an adult rhesus monkey. A continuous epithelial cell line, 816A, was established from a lymph node of an adult rhesus monkey with metastatic esophageal carcinoma. These cells are characterized by the presence of desmosomes and a markedly heteroploid karyotype. At a relatively early culture age, electron microscopy showed both budding and extracellular type C virus. Antigen reactive with antisera to Mason-Pfizer monkey virus was observed by complement-fixation. The level of this antigen decreased with increased culture age. To our knowledge, the 816A cells represent the only established simian or human cell line of esophageal carcinoma origin."}
{"id": "PMID:210935", "title": "Constitutive and inducible granulocyte-macrophage functions in mouse, rat, and human myeloid leukemia-derived continuous tissue culture lines.", "content": "Fourteen continuous tissue culture cell lines derived from mouse, rat, or human granulocyte-macrophage cancers were studied for expression of spontaneous and inducible markers of differentiated cells. Five cell lines (two mouse, two rat, and one human) synthesized myeloperoxidase spontaneously, and a fifth mouse line showed biochemically inducible enzyme. Twelve lines (6 mouse, 3 rat, and 3 human) produced lysozyme (muramidase), and all had detectable beta-glucuronidase. Superoxide generation was detected in one mouse, and three human cell lines following stimulation with phorbol myristate acetate. Maturation to differentiated polymorphonuclear leukocyte or macrophage morphology was induced in 3 cell lines (2 mouse and 1 human) following culture in diffusion chambers in total-body-irradiated rats. In vitro morphological differentiation was inducible in one (mouse) cell line exposed to casein, thioglycolate, or plasma from irradiated rats or mice. These findings indicate that mammalian cell lines derived from granulocyte-macrophage cancers stably express several combinations of differentiation markers. The patterns of expression of these markers did not always correlate with the morphological stage of differentiation.", "contents": "Constitutive and inducible granulocyte-macrophage functions in mouse, rat, and human myeloid leukemia-derived continuous tissue culture lines. Fourteen continuous tissue culture cell lines derived from mouse, rat, or human granulocyte-macrophage cancers were studied for expression of spontaneous and inducible markers of differentiated cells. Five cell lines (two mouse, two rat, and one human) synthesized myeloperoxidase spontaneously, and a fifth mouse line showed biochemically inducible enzyme. Twelve lines (6 mouse, 3 rat, and 3 human) produced lysozyme (muramidase), and all had detectable beta-glucuronidase. Superoxide generation was detected in one mouse, and three human cell lines following stimulation with phorbol myristate acetate. Maturation to differentiated polymorphonuclear leukocyte or macrophage morphology was induced in 3 cell lines (2 mouse and 1 human) following culture in diffusion chambers in total-body-irradiated rats. In vitro morphological differentiation was inducible in one (mouse) cell line exposed to casein, thioglycolate, or plasma from irradiated rats or mice. These findings indicate that mammalian cell lines derived from granulocyte-macrophage cancers stably express several combinations of differentiation markers. The patterns of expression of these markers did not always correlate with the morphological stage of differentiation."}
{"id": "PMID:210938", "title": "Inverse relation between estrogen receptors and cyclic adenosine 3':5'-monophosphate-binding proteins in hormone-dependent mammary tumor regression due to dibutyryl cyclic adenosine 3':5'-monophosphate treatment or ovariectomy.", "content": "During the growth arrest of 7,12-dimethylbenz(alpha) anthracene-induced rat mammary carcinomas following ovariectomy or N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (DBcAMP) treatment, a change in the specific estrogen and cAMP binding to tumor proteins is observed. Three days after ovariectomy or DBcAMP treatment of the hosts, cAMP binding increases 5- and 2-fold in the nuclei and cytosol of tumors, respectively, whereas nuclear and cytoplasmic estrogen binding decreases by 70 and 25%, respectively. These changes in cAMP- and estrogen-binding activities are detectable within 1 day after ovariectomy or DBcAMP treatment, and the changes are reversed when resumption of tumor growth is induced by the injection of estradiol valerate or cessation of DBcAMP treatment. When 7,12-dimethylbenz(alpha)anthracene-induced tumors fail to regress after ovariectomy or DBcAMP treatment, the change in estrogen and cAMP binding does not occur. Concomitant with the increase of cAMP-binding activity in regressing tumors are increases in histone kinase activity and the cAMP content of the tumors. These increases in cAMP-binding and protein kinase activities are blocked by cycloheximide. These data suggest an interaction between a steroid hormone and cAMP in the growth control of a hormone-dependent mammary tumor.", "contents": "Inverse relation between estrogen receptors and cyclic adenosine 3':5'-monophosphate-binding proteins in hormone-dependent mammary tumor regression due to dibutyryl cyclic adenosine 3':5'-monophosphate treatment or ovariectomy. During the growth arrest of 7,12-dimethylbenz(alpha) anthracene-induced rat mammary carcinomas following ovariectomy or N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (DBcAMP) treatment, a change in the specific estrogen and cAMP binding to tumor proteins is observed. Three days after ovariectomy or DBcAMP treatment of the hosts, cAMP binding increases 5- and 2-fold in the nuclei and cytosol of tumors, respectively, whereas nuclear and cytoplasmic estrogen binding decreases by 70 and 25%, respectively. These changes in cAMP- and estrogen-binding activities are detectable within 1 day after ovariectomy or DBcAMP treatment, and the changes are reversed when resumption of tumor growth is induced by the injection of estradiol valerate or cessation of DBcAMP treatment. When 7,12-dimethylbenz(alpha)anthracene-induced tumors fail to regress after ovariectomy or DBcAMP treatment, the change in estrogen and cAMP binding does not occur. Concomitant with the increase of cAMP-binding activity in regressing tumors are increases in histone kinase activity and the cAMP content of the tumors. These increases in cAMP-binding and protein kinase activities are blocked by cycloheximide. These data suggest an interaction between a steroid hormone and cAMP in the growth control of a hormone-dependent mammary tumor."}
{"id": "PMID:210940", "title": "Characterization by molecular hybridization of two viral populations derived from a radiation leukemia virus.", "content": "Two leukemogenic viral populations were derived from a radiation leukemia virus of the C57BL mouse. One (FB), in which only B-tropic virus could be detected, was obtained in vivo by serial passage of cell-free extract in newborn rats. The second (3C), a complex containing at least B-tropic and xenotropic viruses, was produced in vitro by a permanent cell line (13-3C) established from the spleen of a virus-infected C57BL mouse. In molecular hybridization experiments, the 70S RNA of Gross leukemia virus hybridized 96 and 78% of FB and 3C radioactive complementary DNA's, respectively, with a relatively high thermal stability of the duplexes formed. In contrast, the 70S RNA of Rauscher leukemia virus hybridized 23 and 20% of the FB and 3C DNA probes, respectively, with a low thermal stability. The rat-grown FB virions exhibited 50% genome homology with the viruses produced in vitro on the 13-3C cells. Finally, hybridizing the FB and 3C probes with normal or leukemic mouse spleen DNA's resulted in 89 to 100% homology. The rat-grown virions did not appear to contain detectable rat cellular DNA sequences, while about 20 complete copies of their nucleotide sequences were detected in covalent linkage with FB-infected rat spleen DNA. These findings strongly support the endogenous murine origin of the investigated virions.", "contents": "Characterization by molecular hybridization of two viral populations derived from a radiation leukemia virus. Two leukemogenic viral populations were derived from a radiation leukemia virus of the C57BL mouse. One (FB), in which only B-tropic virus could be detected, was obtained in vivo by serial passage of cell-free extract in newborn rats. The second (3C), a complex containing at least B-tropic and xenotropic viruses, was produced in vitro by a permanent cell line (13-3C) established from the spleen of a virus-infected C57BL mouse. In molecular hybridization experiments, the 70S RNA of Gross leukemia virus hybridized 96 and 78% of FB and 3C radioactive complementary DNA's, respectively, with a relatively high thermal stability of the duplexes formed. In contrast, the 70S RNA of Rauscher leukemia virus hybridized 23 and 20% of the FB and 3C DNA probes, respectively, with a low thermal stability. The rat-grown FB virions exhibited 50% genome homology with the viruses produced in vitro on the 13-3C cells. Finally, hybridizing the FB and 3C probes with normal or leukemic mouse spleen DNA's resulted in 89 to 100% homology. The rat-grown virions did not appear to contain detectable rat cellular DNA sequences, while about 20 complete copies of their nucleotide sequences were detected in covalent linkage with FB-infected rat spleen DNA. These findings strongly support the endogenous murine origin of the investigated virions."}
{"id": "PMID:210941", "title": "Aminopeptidase activities on the surface of mammalian cells and their alterations associated with transformation.", "content": "Activities of various hydrolytic enzymes were determined in rat organ homogenates and on the surface of cells from various sources, i.e., tumor cell strains, primary cultured cells, normal cells, and their transformants. Alanine, leucine, methionine, phenylalanine, and glycyl-proline aminopeptidases and esterase showed relatively high activities in all these organs and cells. In the kidney homogenate the aminopeptidase A activity was higher in other organs; i.e., the aminopeptidase A activity was lower than that of aminopeptidase B. Normal cells derived from kidneys showed the kidney-type pattern of amino-peptidases A and B on the surface of cells, whereas tumor cells from various origins were of another organ type. When cultured mouse fibroblast strain C3H2K and rat fibroblast strain 3Y1 cells were transformed by SV40 or by a ts A mutant and maintained at permissive temperature, aminopeptidase A activity was drastically decreased, and the ratio of aminopeptidase A to aminopeptidase B was reduced to the levels of tumor cells. If the ts A mutant-transformed cells were grown at the restrictive temperature, the ratio approached that of normal cells. In normal cells, however, cultivation at high or low temperature did not cause any change of the activities.", "contents": "Aminopeptidase activities on the surface of mammalian cells and their alterations associated with transformation. Activities of various hydrolytic enzymes were determined in rat organ homogenates and on the surface of cells from various sources, i.e., tumor cell strains, primary cultured cells, normal cells, and their transformants. Alanine, leucine, methionine, phenylalanine, and glycyl-proline aminopeptidases and esterase showed relatively high activities in all these organs and cells. In the kidney homogenate the aminopeptidase A activity was higher in other organs; i.e., the aminopeptidase A activity was lower than that of aminopeptidase B. Normal cells derived from kidneys showed the kidney-type pattern of amino-peptidases A and B on the surface of cells, whereas tumor cells from various origins were of another organ type. When cultured mouse fibroblast strain C3H2K and rat fibroblast strain 3Y1 cells were transformed by SV40 or by a ts A mutant and maintained at permissive temperature, aminopeptidase A activity was drastically decreased, and the ratio of aminopeptidase A to aminopeptidase B was reduced to the levels of tumor cells. If the ts A mutant-transformed cells were grown at the restrictive temperature, the ratio approached that of normal cells. In normal cells, however, cultivation at high or low temperature did not cause any change of the activities."}
{"id": "PMID:210942", "title": "A greatly simplified method of establishing B-lymphoblastoid cell lines.", "content": "Ten lymphoblastoid cell lines were established by Epstein-Barr virus-induced transformation directly from 0.04 to 0.15 ml of peripheral whole blood of one patient with xeroderma pigmentosum and four normal healthy adults. All these lines expressed B-lymphocyte characteristics. The advantages of this method are: (a) only a few drops of blood are required for establishing a permanent line; (b) damage and loss of cells in separation procedures are minimal; and (c) the method is simple, reliable, and applicable, if desired, to any patient, even babies.", "contents": "A greatly simplified method of establishing B-lymphoblastoid cell lines. Ten lymphoblastoid cell lines were established by Epstein-Barr virus-induced transformation directly from 0.04 to 0.15 ml of peripheral whole blood of one patient with xeroderma pigmentosum and four normal healthy adults. All these lines expressed B-lymphocyte characteristics. The advantages of this method are: (a) only a few drops of blood are required for establishing a permanent line; (b) damage and loss of cells in separation procedures are minimal; and (c) the method is simple, reliable, and applicable, if desired, to any patient, even babies."}
{"id": "PMID:210949", "title": "Changes in the adrenal cortex of the rat after chronic administration of the steroidogenic inhibitor U-8113.", "content": "In concert with studies of the effects of various pharmacologic inhibitors of corticosteroidogenesis on adrenocortical morphology, U-8113, an analog of amphenone B, was administered daily to Sprague-Dawley rats for 7, 14, 21 or 30 day. The primary morphological responses involved increases in adrenal weight, width of zona fasciculata, width of zona reticularis, intracellular lipids, mitochondrial size, mitochondrial vacuolation and crystalline-like inclusions, small coated vesicles, lysosomes, autophagic vacuoles and cholesterol ester clefts. In particular, the increases in lysosomes, coated vesicles and autophagic vacuoles containing morphologically altered mitochondria were considered reflective of mechanisms designed to maintain cellular integrity amidst functional impairment. Lipid analysis revealed marked increases in cholesterol esters and phospholipids, supportive of morphological observations. When permitted a 14 day recovery period following either 14 or 30 days of inhibitor therapy, most fine structural alterations and lipid derangements were diminished, and the cells approximated normal parameters.", "contents": "Changes in the adrenal cortex of the rat after chronic administration of the steroidogenic inhibitor U-8113. In concert with studies of the effects of various pharmacologic inhibitors of corticosteroidogenesis on adrenocortical morphology, U-8113, an analog of amphenone B, was administered daily to Sprague-Dawley rats for 7, 14, 21 or 30 day. The primary morphological responses involved increases in adrenal weight, width of zona fasciculata, width of zona reticularis, intracellular lipids, mitochondrial size, mitochondrial vacuolation and crystalline-like inclusions, small coated vesicles, lysosomes, autophagic vacuoles and cholesterol ester clefts. In particular, the increases in lysosomes, coated vesicles and autophagic vacuoles containing morphologically altered mitochondria were considered reflective of mechanisms designed to maintain cellular integrity amidst functional impairment. Lipid analysis revealed marked increases in cholesterol esters and phospholipids, supportive of morphological observations. When permitted a 14 day recovery period following either 14 or 30 days of inhibitor therapy, most fine structural alterations and lipid derangements were diminished, and the cells approximated normal parameters."}
{"id": "PMID:210950", "title": "Ultrastructural demonstration of hormone-induced movement of carotenoid droplets and endoplasmic reticulum in xanthophores of the goldfish, Carassius auratus L.", "content": "The hormone-induced pigment dispersion in primary cultures of xanthophores of goldfish (Carassius auratus L.) has been shown to involve the dispersion of not only carotenoid droplets but also of smooth endoplasmic reticulum. The dispersion of these organelles is inhibited by cytochalasin B and is accompanied by thinning of the cell body, thickening of the processes, and also overall changes in cellular morphology (process extension) under certain conditions. Electron microscopic examination of heavy meromyosin treated glycerinated xanthophores in scales revealed the presence of actin filaments in these cells.", "contents": "Ultrastructural demonstration of hormone-induced movement of carotenoid droplets and endoplasmic reticulum in xanthophores of the goldfish, Carassius auratus L. The hormone-induced pigment dispersion in primary cultures of xanthophores of goldfish (Carassius auratus L.) has been shown to involve the dispersion of not only carotenoid droplets but also of smooth endoplasmic reticulum. The dispersion of these organelles is inhibited by cytochalasin B and is accompanied by thinning of the cell body, thickening of the processes, and also overall changes in cellular morphology (process extension) under certain conditions. Electron microscopic examination of heavy meromyosin treated glycerinated xanthophores in scales revealed the presence of actin filaments in these cells."}
{"id": "PMID:210951", "title": "Discrimination of LH, FSH, TSH and ACTH in dissociated porcine anterior pituitary cells by light and electron microscope immunocytochemistry.", "content": "Using the PAP unlabelled antibody method, LH, FSH, TSH and ACTH were localized at light microscope level in cultured cells dissociated from the porcine adenohypophysis. Antisera were shown to be specific for the beta-subunits of the porcine glycoprotein hormones by radioimmunoassay and absorption studies. Using these antisera, it was found that LH and FSH were contained within the same cell, with TSH in a separate cell. When absorbed with LH, anti-porcine ACTH stained a separate distinct population of ACTH cells. Adjacent ultra-thin sections stained with anti-pLH beta and anti-pFSH beta, and examined at electron microscope level, showed that the ovoid, 150--400nm secretory granules of the LH/FSH gonadotrophs contained both LH and FSH.", "contents": "Discrimination of LH, FSH, TSH and ACTH in dissociated porcine anterior pituitary cells by light and electron microscope immunocytochemistry. Using the PAP unlabelled antibody method, LH, FSH, TSH and ACTH were localized at light microscope level in cultured cells dissociated from the porcine adenohypophysis. Antisera were shown to be specific for the beta-subunits of the porcine glycoprotein hormones by radioimmunoassay and absorption studies. Using these antisera, it was found that LH and FSH were contained within the same cell, with TSH in a separate cell. When absorbed with LH, anti-porcine ACTH stained a separate distinct population of ACTH cells. Adjacent ultra-thin sections stained with anti-pLH beta and anti-pFSH beta, and examined at electron microscope level, showed that the ovoid, 150--400nm secretory granules of the LH/FSH gonadotrophs contained both LH and FSH."}
{"id": "PMID:210952", "title": "Possible relationship between the activity of the adrenal gland and the subcommissural organ in the lizard Lacerta s. sicula Raf. Effects of ACTH Administration during winter.", "content": "In order to study the possible functional relationship between the adrenal gland and the subcommissural organ (SCO) in the lizard Lacerta s. sicula Raf., ACTH was administered to some specimens of this species in January when both the adrenal gland and the subcommissural organ have a very low activity. In comparison to untreated controls, the adrenals of animals treated with ACTH showed clear signs of stimulation, presenting enlarged blood vessels, very few lipid droplets, numerous polymorphic mitochondria and abundant tubular smooth endoplasmic reticulum. In addition, a distinct increase in secretory material was observed in the subcommissural cells of specimens treated with ACTH. These cells showed large cisternae of the rough endoplasmic reticulum filled with granular material in the basal region, numerous secretory granules of two types in the paical region and a reduced number of microvilli on the free cell surface. These findings, together with the results of preceding studies, lead the authors to the consideration that steroid hormones might play a role in the regulation of the secretory activity of the SCO.", "contents": "Possible relationship between the activity of the adrenal gland and the subcommissural organ in the lizard Lacerta s. sicula Raf. Effects of ACTH Administration during winter. In order to study the possible functional relationship between the adrenal gland and the subcommissural organ (SCO) in the lizard Lacerta s. sicula Raf., ACTH was administered to some specimens of this species in January when both the adrenal gland and the subcommissural organ have a very low activity. In comparison to untreated controls, the adrenals of animals treated with ACTH showed clear signs of stimulation, presenting enlarged blood vessels, very few lipid droplets, numerous polymorphic mitochondria and abundant tubular smooth endoplasmic reticulum. In addition, a distinct increase in secretory material was observed in the subcommissural cells of specimens treated with ACTH. These cells showed large cisternae of the rough endoplasmic reticulum filled with granular material in the basal region, numerous secretory granules of two types in the paical region and a reduced number of microvilli on the free cell surface. These findings, together with the results of preceding studies, lead the authors to the consideration that steroid hormones might play a role in the regulation of the secretory activity of the SCO."}
{"id": "PMID:210953", "title": "The demonstration of cells bearing Fc receptors in the metrial gland of the pregnant rat uterus.", "content": "Cells obtained by collagenase treatment of metrial gland tissue from rats of day 12, 13, 14 and 15 of pregnancy were examined for the presence of surface membrane receptors for immunoglobulin (Fc receptors). Using an EA rosetting technique in which sheep red blood cells (SRBC) were sensitized with a rabbit anti-SRBC immunoglobulin preparation, Fc receptors were found on a proportion of the cells. The majority of the granulated metrial gland cells were not included in the rosetting cell population, suggesting that they do not possess the type of Fc receptor detected by this method. A comparison was made between results obtained when cells were counted in suspension and those obtained from cell counts on sections of fixed material. Both methods were found to yield similar results.", "contents": "The demonstration of cells bearing Fc receptors in the metrial gland of the pregnant rat uterus. Cells obtained by collagenase treatment of metrial gland tissue from rats of day 12, 13, 14 and 15 of pregnancy were examined for the presence of surface membrane receptors for immunoglobulin (Fc receptors). Using an EA rosetting technique in which sheep red blood cells (SRBC) were sensitized with a rabbit anti-SRBC immunoglobulin preparation, Fc receptors were found on a proportion of the cells. The majority of the granulated metrial gland cells were not included in the rosetting cell population, suggesting that they do not possess the type of Fc receptor detected by this method. A comparison was made between results obtained when cells were counted in suspension and those obtained from cell counts on sections of fixed material. Both methods were found to yield similar results."}
{"id": "PMID:210954", "title": "Isolation and characterization of a siderophore-like growth factor from mutants of SV40-transformed cells adapted to picolinic acid.", "content": "We have isolated mutants of SV40-transformed BALB/3T3 cells adapted to grow in picolinic acid. A line of cells, derived from the mutant cells, that multiplies in the absence of serum has also been characterized. From ultrafiltrates of medium conditioned by contact with these cell lines, we have identified and partially purified a highly specific iron-binding ligand termed siderophore-like growth factor (SGF). Experiments have indicated that the factor is a peptide(s) of approximately 1600 daltons. In nanogram amounts, SGF solubilizes and binds Fe 3+ in vitro and stimulates the uptake of Fe 3+ in vivo. The Fe 3+ uptake preceded the stimulation of DNA synthesis induced by the factor in the mutant cell lines. The factor could not be separated into Fe 3+ binding and DNA synthetic activity, suggesting that the early iron uptake is an integral component of the proliferative response. These data support the hypothesis that SGF is representative of a family of mammalian siderophores which may have an important role in cell proliferation.", "contents": "Isolation and characterization of a siderophore-like growth factor from mutants of SV40-transformed cells adapted to picolinic acid. We have isolated mutants of SV40-transformed BALB/3T3 cells adapted to grow in picolinic acid. A line of cells, derived from the mutant cells, that multiplies in the absence of serum has also been characterized. From ultrafiltrates of medium conditioned by contact with these cell lines, we have identified and partially purified a highly specific iron-binding ligand termed siderophore-like growth factor (SGF). Experiments have indicated that the factor is a peptide(s) of approximately 1600 daltons. In nanogram amounts, SGF solubilizes and binds Fe 3+ in vitro and stimulates the uptake of Fe 3+ in vivo. The Fe 3+ uptake preceded the stimulation of DNA synthesis induced by the factor in the mutant cell lines. The factor could not be separated into Fe 3+ binding and DNA synthetic activity, suggesting that the early iron uptake is an integral component of the proliferative response. These data support the hypothesis that SGF is representative of a family of mammalian siderophores which may have an important role in cell proliferation."}
{"id": "PMID:210955", "title": "Cellular alterations dependent upon the polyoma virus Hr-t function: separation of mitogenic from transforming capacities.", "content": "Hr-t mutants of polyoma virus are restricted in their growth properties (host range) and defective in cell transformation and tumor induction. The present study indicates that these mutants have lost the ability to induce morphological transformation, but have retained a mitogenic function. Thus an early and dramatic difference between wild-type virus and hr-t mutant-infected cultures of rat fibroblasts is the morphological change in individual cells observed by light, fluorescence and scanning electron microscopy. Viruses containing an intact hr-t function (wild-type virus and ts-a mutants) induce a transformed phenotype consisting of stellate cell shape, loss of defined cytoplasmic actin architecture, cellular \"underlapping,\" and increased nuclear and nucleolar sizes. These prominent alterations constitute an abortive transformation, peaking 24-48 hr post-infection, and subsequently resolving in most or all of the cells. In contrast, cells infected with hr-t mutants do not develop the above structural changes, but rather retain their preinfection appearance. Both wild-type virus and hr-t mutants induce cellular DNA synthesis in confluent monolayers of rat cells beginning 12-14 hr post-infection. Flow microfluorometric (FMF) analysis confirms the viral mediated transit of cells from the G1 to the S and G2 phases of the cell cycle, as well as an increase in the proportion of cells with an 8N (octaploid) DNA content. Approximately 50% of the clones isolated from wild-type-infected cultures are polyploid. Stable transformants are found among these polyploid clones, but the majority of the latter resemble the parental cells in their morphology and growth properties. Polyploid clones are derived from hr-t mutant-infected cultures at a much lower frequency, similar to that of mock-infected cultures. Data obtained by sequential labeling of infected cultures with 3 H-thymidine and 5-bromo-deoxyuridine, together with cell number quantitation, indicate that hr-t mutants promote only a single round of cell division, while the wild-type virus and ts-a mutants promote multiple rounds. Loss of the hr-t function in polyoma virus therefore reveals a residual viral mitogenic activity, but prevents the virus from effecting morphological transformation of cells with concomitant loss of defined actin cables, polyploidization and multiple cycles of cell division in confluent cultures.", "contents": "Cellular alterations dependent upon the polyoma virus Hr-t function: separation of mitogenic from transforming capacities. Hr-t mutants of polyoma virus are restricted in their growth properties (host range) and defective in cell transformation and tumor induction. The present study indicates that these mutants have lost the ability to induce morphological transformation, but have retained a mitogenic function. Thus an early and dramatic difference between wild-type virus and hr-t mutant-infected cultures of rat fibroblasts is the morphological change in individual cells observed by light, fluorescence and scanning electron microscopy. Viruses containing an intact hr-t function (wild-type virus and ts-a mutants) induce a transformed phenotype consisting of stellate cell shape, loss of defined cytoplasmic actin architecture, cellular \"underlapping,\" and increased nuclear and nucleolar sizes. These prominent alterations constitute an abortive transformation, peaking 24-48 hr post-infection, and subsequently resolving in most or all of the cells. In contrast, cells infected with hr-t mutants do not develop the above structural changes, but rather retain their preinfection appearance. Both wild-type virus and hr-t mutants induce cellular DNA synthesis in confluent monolayers of rat cells beginning 12-14 hr post-infection. Flow microfluorometric (FMF) analysis confirms the viral mediated transit of cells from the G1 to the S and G2 phases of the cell cycle, as well as an increase in the proportion of cells with an 8N (octaploid) DNA content. Approximately 50% of the clones isolated from wild-type-infected cultures are polyploid. Stable transformants are found among these polyploid clones, but the majority of the latter resemble the parental cells in their morphology and growth properties. Polyploid clones are derived from hr-t mutant-infected cultures at a much lower frequency, similar to that of mock-infected cultures. Data obtained by sequential labeling of infected cultures with 3 H-thymidine and 5-bromo-deoxyuridine, together with cell number quantitation, indicate that hr-t mutants promote only a single round of cell division, while the wild-type virus and ts-a mutants promote multiple rounds. Loss of the hr-t function in polyoma virus therefore reveals a residual viral mitogenic activity, but prevents the virus from effecting morphological transformation of cells with concomitant loss of defined actin cables, polyploidization and multiple cycles of cell division in confluent cultures."}
{"id": "PMID:210956", "title": "Identification and isolation of the yeast cytochrome c gene.", "content": "The iso-1-cytochrome c gene of yeast has been identified and cloned using a synthetic oligodeoxynucleotide as a hybridization probe. The oligomer d[pT-T-A-G-C-A-G-A-A--C-C-G-G] is complementary to a region near the N terminal coding region of the yeast cyc 1 gene. Of several yeast Eco RI fragments which hybridize to this probe, one is changed in size by a G leads to T mutation which eliminates an Eco RI site within the cyc 1 gene. Both the wild-type and the RI- mutant forms were cloned in lambda gt vectors. Maxam-Gilbert sequencing for 91 nucleotides into the coding region for iso-1-cytochrome c yielded a DNA sequence in perfect correspondence with the known protein sequence.", "contents": "Identification and isolation of the yeast cytochrome c gene. The iso-1-cytochrome c gene of yeast has been identified and cloned using a synthetic oligodeoxynucleotide as a hybridization probe. The oligomer d[pT-T-A-G-C-A-G-A-A--C-C-G-G] is complementary to a region near the N terminal coding region of the yeast cyc 1 gene. Of several yeast Eco RI fragments which hybridize to this probe, one is changed in size by a G leads to T mutation which eliminates an Eco RI site within the cyc 1 gene. Both the wild-type and the RI- mutant forms were cloned in lambda gt vectors. Maxam-Gilbert sequencing for 91 nucleotides into the coding region for iso-1-cytochrome c yielded a DNA sequence in perfect correspondence with the known protein sequence."}
{"id": "PMID:210957", "title": "Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor.", "content": "Previous studies from our laboratories have demonstrated the feasibility of transferring the thymidine kinase (tk) gene from restriction endonuclease-generated fragments of herpes simplex virus (HSV) DNA to cultured mammalian cells. In this study, high molecular weight DNA from cells containing only one copy of the HSV gene coding for tk was successfully used to transform L+K-cells to the tk+ phenotype. The acquired phenotype was demonstrated to be donor-derived by analysis of the electrophoretic mobility of the tk activity, and the presence of HSV DNA sequences in the recipient cells was demonstrated. In companion experiments, we used high molecular weight DNA derived from tissues and cultured cells of a variety of species to transfer tk activity. The tk+ mouse cells transformed with human DNA were shown to express human type tk activity as determined by isoelectric focusing.", "contents": "Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor. Previous studies from our laboratories have demonstrated the feasibility of transferring the thymidine kinase (tk) gene from restriction endonuclease-generated fragments of herpes simplex virus (HSV) DNA to cultured mammalian cells. In this study, high molecular weight DNA from cells containing only one copy of the HSV gene coding for tk was successfully used to transform L+K-cells to the tk+ phenotype. The acquired phenotype was demonstrated to be donor-derived by analysis of the electrophoretic mobility of the tk activity, and the presence of HSV DNA sequences in the recipient cells was demonstrated. In companion experiments, we used high molecular weight DNA derived from tissues and cultured cells of a variety of species to transfer tk activity. The tk+ mouse cells transformed with human DNA were shown to express human type tk activity as determined by isoelectric focusing."}
{"id": "PMID:210958", "title": "Differential expression of Rous Sarcoma virus-specific transformation parameters in enucleated cells.", "content": "Chicken embryo fibroblasts transformed with the Ta and ts68 mutants of Rous Sarcoma virus (RSV) were enucleated and studied for their capacity to express reversibly the transformed phenotype in response to temperature changes. After shift to the permissive temperature (35 degrees C), the cytoplasts acquired a transformed morphology and displayed characteristic ruffles and microvilli at their surface. As detected by immunofluorescence, they also lost their actin filament cables and exhibited characteristic changes in the pattern of cell surface structures containing LETS protein. Expression of all these transformation parameters was reversible after shiftback to the nonpermissive temperature (41 degrees C). These results indicate that a whole set of changes characteristic for the transformed phenotype can be expressed independently of the cell nucleus. In contrast, ts mutant-infected cytoplasts were no longer able to respond to temperature shifts with changes in their hexose transport rate. Cytoplasts prepared from cells grown at 41 degrees C retained their low rate of hexose uptake after shift to 35 degrees C, whereas cytoplasts from cells grown at 35 degrees C exhibited a high rate of hexose transport even after 10 hr of shift to 41 degrees C. These results are in accordance with the hypothesis that the product of the src gene of RSV represents a multifunctional protein which acts independently on nuclear and extranuclear sites.", "contents": "Differential expression of Rous Sarcoma virus-specific transformation parameters in enucleated cells. Chicken embryo fibroblasts transformed with the Ta and ts68 mutants of Rous Sarcoma virus (RSV) were enucleated and studied for their capacity to express reversibly the transformed phenotype in response to temperature changes. After shift to the permissive temperature (35 degrees C), the cytoplasts acquired a transformed morphology and displayed characteristic ruffles and microvilli at their surface. As detected by immunofluorescence, they also lost their actin filament cables and exhibited characteristic changes in the pattern of cell surface structures containing LETS protein. Expression of all these transformation parameters was reversible after shiftback to the nonpermissive temperature (41 degrees C). These results indicate that a whole set of changes characteristic for the transformed phenotype can be expressed independently of the cell nucleus. In contrast, ts mutant-infected cytoplasts were no longer able to respond to temperature shifts with changes in their hexose transport rate. Cytoplasts prepared from cells grown at 41 degrees C retained their low rate of hexose uptake after shift to 35 degrees C, whereas cytoplasts from cells grown at 35 degrees C exhibited a high rate of hexose transport even after 10 hr of shift to 41 degrees C. These results are in accordance with the hypothesis that the product of the src gene of RSV represents a multifunctional protein which acts independently on nuclear and extranuclear sites."}
{"id": "PMID:210959", "title": "Regulation of expression and chromosomal subunit conformation of avian retrovirus genomes.", "content": "We have investigated the copy number, chromosomal subunit conformation and regulation of expression of integrated avian retrovirus genomes. Our results indicate that there are approximately two copies of the endogenous viral genomes (RAV-O) per haploid cell genome in uninfected chick embryo fibroblasts (CEF) and red blood cells (RBC). The copy number and subunit conformation (as measured by DNAasel sensitivity) of the RAV-O genomes are independent of the level of expression of these viral DNA sequences. In cells isolated from embryos of the V+, gs-chf- and gs+chf+ phenotypes, approximately one of the two viral genomes is in a DNAase l-sensitive conformation. Upon infection with an exogenous Rous sarcoma virus (PR-RSV-C), one new viral genome is integrated per haploid CEF genome. The newly integrated RSV genome is completely sensitive to DNAase l, and the subunit conformation of the endogenous viral genomes is not altered by the integration of additional exogenous proviruses. Both the endogenous and newly integrated exogenous viral genomes are present in \"nu-body\" structures, and the selective sensitivity of these proviral DNA sequences to DNAase l is maintained in isolated nucleosomes. Our experiments revealing the DNAase l sensitivity of one of the two RAV-O genomes in gs-chf-CEF led us to reexamine the level of viral specific RNA in CEF of various GS genotypes. We find that GS/GS CEF contain approximately 100 copies of viral RNA per cell, gs/gs CEF contain no detectable viral RNA, and the heterozygote GS/gs CEF contain approximately 50 copies of viral specific RNA per cell. These results suggest that the GS gene controls production of RAV-O RNA sequences in CEF in a \"cis\" fashion. In RBCs, however, the expression of the RAV-O genome is independent of the GS gene, with both GS/GS and gs/gs RBCs containing roughly equivalent amounts of viral specific RNA. Our results suggest that the chromosomal structure of the endogenous viral genes is independent of the GS gene, and that the GS gene is cis-acting and tissue-specific.", "contents": "Regulation of expression and chromosomal subunit conformation of avian retrovirus genomes. We have investigated the copy number, chromosomal subunit conformation and regulation of expression of integrated avian retrovirus genomes. Our results indicate that there are approximately two copies of the endogenous viral genomes (RAV-O) per haploid cell genome in uninfected chick embryo fibroblasts (CEF) and red blood cells (RBC). The copy number and subunit conformation (as measured by DNAasel sensitivity) of the RAV-O genomes are independent of the level of expression of these viral DNA sequences. In cells isolated from embryos of the V+, gs-chf- and gs+chf+ phenotypes, approximately one of the two viral genomes is in a DNAase l-sensitive conformation. Upon infection with an exogenous Rous sarcoma virus (PR-RSV-C), one new viral genome is integrated per haploid CEF genome. The newly integrated RSV genome is completely sensitive to DNAase l, and the subunit conformation of the endogenous viral genomes is not altered by the integration of additional exogenous proviruses. Both the endogenous and newly integrated exogenous viral genomes are present in \"nu-body\" structures, and the selective sensitivity of these proviral DNA sequences to DNAase l is maintained in isolated nucleosomes. Our experiments revealing the DNAase l sensitivity of one of the two RAV-O genomes in gs-chf-CEF led us to reexamine the level of viral specific RNA in CEF of various GS genotypes. We find that GS/GS CEF contain approximately 100 copies of viral RNA per cell, gs/gs CEF contain no detectable viral RNA, and the heterozygote GS/gs CEF contain approximately 50 copies of viral specific RNA per cell. These results suggest that the GS gene controls production of RAV-O RNA sequences in CEF in a \"cis\" fashion. In RBCs, however, the expression of the RAV-O genome is independent of the GS gene, with both GS/GS and gs/gs RBCs containing roughly equivalent amounts of viral specific RNA. Our results suggest that the chromosomal structure of the endogenous viral genes is independent of the GS gene, and that the GS gene is cis-acting and tissue-specific."}
{"id": "PMID:210960", "title": "Heteroduplex analysis of the nonhomology region between Moloney MuLV and the dual host range derivative HIX virus.", "content": "The dual host range virus HIX has been previously characterized as an envelope gene recombinant between Moloney murine leukemia virus (Mo-MuLV) and an unidentified xenotropic murine leukemia virus. Using long reverse transcripts of Mo-MuLV, a region of nonhomology has been mapped by electron microscopic analysis of heteroduplexes formed with HIX 35S virion RNA. In this nonhomology region, the Mo-MuLV cDNA strand measured approximately 900 nucleotides, mapping between 1.6 and 2.5 kilobases from the 3' end. In  a previous study, hybridization of Mo-MuLV 21S RNA with Mo-MuLV cDNA resulted in the formation of different heteroduplex structures diagnostic of a noncontiguously coded leader sequence at the 5' end of the 21S RNA. Following hybridization of poly(A)+ HIX 21S RAN with 8.2 kb Mo-MuLV cDNA, analogous heteroduplex structures were observed exhibiting the Mo-MuLV:HIX substitution loop in the DNA:RNA segment of the molecules. This analysis permitted more precise mapping of the nonhomology region with respect to the splice point in the 21S presumptive glycoprotein mRNA. The mapping of this nonhomology region in HIX virus provides an internal visual marker for the 3' end of the genome which may prove useful in future analyses of other deletion or substitution derivatives of Mo-MuLV.", "contents": "Heteroduplex analysis of the nonhomology region between Moloney MuLV and the dual host range derivative HIX virus. The dual host range virus HIX has been previously characterized as an envelope gene recombinant between Moloney murine leukemia virus (Mo-MuLV) and an unidentified xenotropic murine leukemia virus. Using long reverse transcripts of Mo-MuLV, a region of nonhomology has been mapped by electron microscopic analysis of heteroduplexes formed with HIX 35S virion RNA. In this nonhomology region, the Mo-MuLV cDNA strand measured approximately 900 nucleotides, mapping between 1.6 and 2.5 kilobases from the 3' end. In  a previous study, hybridization of Mo-MuLV 21S RNA with Mo-MuLV cDNA resulted in the formation of different heteroduplex structures diagnostic of a noncontiguously coded leader sequence at the 5' end of the 21S RNA. Following hybridization of poly(A)+ HIX 21S RAN with 8.2 kb Mo-MuLV cDNA, analogous heteroduplex structures were observed exhibiting the Mo-MuLV:HIX substitution loop in the DNA:RNA segment of the molecules. This analysis permitted more precise mapping of the nonhomology region with respect to the splice point in the 21S presumptive glycoprotein mRNA. The mapping of this nonhomology region in HIX virus provides an internal visual marker for the 3' end of the genome which may prove useful in future analyses of other deletion or substitution derivatives of Mo-MuLV."}
{"id": "PMID:210961", "title": "Mapping the spliced and unspliced late lytic SV40 RNAs.", "content": "The sizes and map positions of the major late lytic SV40 cytoplasmic mRNAs and the abundant nuclear RNA species have been determined by the technique of Berk and Sharp (1977, 1978). From these experiments, the coding sequences (bodies) of the 16S and 19S late cytoplasmic SV40 RNAs have been located at 0.935-0.17 and 0.765-0.17 map units, respectively. The cytoplasmic 16S RNA molecules contain a leader sequence of approximately 210 nucleotides, corresponding to SV40 map positions 0.72-0.76 units, spliced to the coding sequences. In a population of the late 19S RNA molecules, there are several different leader segments, each spliced to the same coding sequences. The size of these 19S leader RNA segments was estimated to be 50-70, 100-120 and 200-210 nucleotides in length. The 5' ends of the 19S leader RNA segments were located at 0.72, 0.71, 0.695 and 0.69 map units. An analysis of the nuclear viral RNAs has provided insight into the biogenesis of the cytoplasmic messages. Poly (A)-containing nuclear RNA has a number of species in addition to those found in the cytoplasm. The 3' ends of the poly (A)-containing RNAs map at 0.17 SV40 units. The 5' ends of the more abundant nuclear molecules map approximately at 0.72, 0.70, 0.67, 0.64 and 0.59 units. Since these nuclear SV40 RNA molecules are both colinear with the viral DNA and larger than the cytoplasmic nRNAs, they may represent intermediates in a stepwise processing system. Alternatively, the variation in 5' ends of nuclear SV40 transcripts may represent a number of separate initiation sites for transcription. The presence of the intervening RNA sequences (between the leader and the coding sequences of the mature mRNAs) in these nuclear RNA molecules suggests that the synthesis of \"spliced\" SV40 RNA involves the direct transcription of the DNA sequences and the subsequent splicing out of the intervening seqment of RNA. Evaluation of the more abundant nonpolyadenylated nuclear RNA molecules showed that they have the same 5' ends as the poly (A)-containing nuclear RNAs. The 3' ends of the nonpolyadenylated RNA molecules map heterogeneously in a broad region extending beyond 0.28 map units. The presence of these long nuclear viral transcripts suggests that transcription of late SV40 RNA does not terminate at 0.17 map units. The location of poly (A) in mature cytoplasmic viral RNA at 0.17 map units suggest that poly (A) addition to RNA molecules may occur by a specific cleavage of the longer transcripts. Based on these analyses, we propose that the longer nonpolyadenylated viral RNA molecules in the nuclei of SV40-infected cells may represent the primary transcripts. While their 5' termini are being processed, the specific addition of poly (A) at 0.17 map units takes place. The polyadenylation of RNA is followed by splicing events to generate the cytoplasmic forms of SV40 mRNA.", "contents": "Mapping the spliced and unspliced late lytic SV40 RNAs. The sizes and map positions of the major late lytic SV40 cytoplasmic mRNAs and the abundant nuclear RNA species have been determined by the technique of Berk and Sharp (1977, 1978). From these experiments, the coding sequences (bodies) of the 16S and 19S late cytoplasmic SV40 RNAs have been located at 0.935-0.17 and 0.765-0.17 map units, respectively. The cytoplasmic 16S RNA molecules contain a leader sequence of approximately 210 nucleotides, corresponding to SV40 map positions 0.72-0.76 units, spliced to the coding sequences. In a population of the late 19S RNA molecules, there are several different leader segments, each spliced to the same coding sequences. The size of these 19S leader RNA segments was estimated to be 50-70, 100-120 and 200-210 nucleotides in length. The 5' ends of the 19S leader RNA segments were located at 0.72, 0.71, 0.695 and 0.69 map units. An analysis of the nuclear viral RNAs has provided insight into the biogenesis of the cytoplasmic messages. Poly (A)-containing nuclear RNA has a number of species in addition to those found in the cytoplasm. The 3' ends of the poly (A)-containing RNAs map at 0.17 SV40 units. The 5' ends of the more abundant nuclear molecules map approximately at 0.72, 0.70, 0.67, 0.64 and 0.59 units. Since these nuclear SV40 RNA molecules are both colinear with the viral DNA and larger than the cytoplasmic nRNAs, they may represent intermediates in a stepwise processing system. Alternatively, the variation in 5' ends of nuclear SV40 transcripts may represent a number of separate initiation sites for transcription. The presence of the intervening RNA sequences (between the leader and the coding sequences of the mature mRNAs) in these nuclear RNA molecules suggests that the synthesis of \"spliced\" SV40 RNA involves the direct transcription of the DNA sequences and the subsequent splicing out of the intervening seqment of RNA. Evaluation of the more abundant nonpolyadenylated nuclear RNA molecules showed that they have the same 5' ends as the poly (A)-containing nuclear RNAs. The 3' ends of the nonpolyadenylated RNA molecules map heterogeneously in a broad region extending beyond 0.28 map units. The presence of these long nuclear viral transcripts suggests that transcription of late SV40 RNA does not terminate at 0.17 map units. The location of poly (A) in mature cytoplasmic viral RNA at 0.17 map units suggest that poly (A) addition to RNA molecules may occur by a specific cleavage of the longer transcripts. Based on these analyses, we propose that the longer nonpolyadenylated viral RNA molecules in the nuclei of SV40-infected cells may represent the primary transcripts. While their 5' termini are being processed, the specific addition of poly (A) at 0.17 map units takes place. The polyadenylation of RNA is followed by splicing events to generate the cytoplasmic forms of SV40 mRNA."}
{"id": "PMID:210962", "title": "Phenotypic complementation of the SV40 tsA mutant defect in viral DNA synthesis following microinjection of SV40 T antigen.", "content": "African green monkey cells (CV-1P) were microinjected with highly purified SV40 T antigen using protein-loaded red cell ghosts and polyethylene glycol as fusagen. The microinjected cells were infected  with a temperature-sensitive mutant of SV40 (tsA209) which is defective in the initiation of viral DNA synthesis. Using in situ hybridization as an assay method, we found that PEG-microinjection of both partially and highly purified T antigen resulted in an increase in the amount of viral DNA sequences in the monolayer. Moreover, 3H-thymidine-labeled and unlabeled Hirt supernatant from microinjected, tsA209-injected cells contained significantly more SV40 DNA than comparable extracts from sham-injected, tsA209-infected or uninfected cells, which were tested in parallel. Thus the introduction of highly purified, \"large\" SV40 T antigen led to phenotypic complementation of the tsA defect in viral DNA synthesis.", "contents": "Phenotypic complementation of the SV40 tsA mutant defect in viral DNA synthesis following microinjection of SV40 T antigen. African green monkey cells (CV-1P) were microinjected with highly purified SV40 T antigen using protein-loaded red cell ghosts and polyethylene glycol as fusagen. The microinjected cells were infected  with a temperature-sensitive mutant of SV40 (tsA209) which is defective in the initiation of viral DNA synthesis. Using in situ hybridization as an assay method, we found that PEG-microinjection of both partially and highly purified T antigen resulted in an increase in the amount of viral DNA sequences in the monolayer. Moreover, 3H-thymidine-labeled and unlabeled Hirt supernatant from microinjected, tsA209-injected cells contained significantly more SV40 DNA than comparable extracts from sham-injected, tsA209-infected or uninfected cells, which were tested in parallel. Thus the introduction of highly purified, \"large\" SV40 T antigen led to phenotypic complementation of the tsA defect in viral DNA synthesis."}
{"id": "PMID:210963", "title": "[Changes in the composition of glycolipids in N-nitrosomorpholine-induced hepatoma. The role of such substances in the plasma membrane of normal and neoplastic cells].", "content": "Malignant hepatomas induced in the rat by N-Nitrosomorpholine showed an absence of trisialogangliosides GT1 and, in some cases, also a decrease in disialoganglioside GD1a and monoganglioside GM1. Simultaneously there occurred an increase in a monoganglioside with a short oligosacharide chain GM3. Such deviations in the composition of glycolipids are in accordance with the literary data mentioning, as a general change, the presence of only some glycolipids as a result of a deficient synthesis of the oligosacharide part of their molecule. The differences in the glycolipid composition of the cell membrane as well as their different arrangement have been discussed with respect to some present views concerning the different behaviour of the neoplastic cell surfaces.", "contents": "[Changes in the composition of glycolipids in N-nitrosomorpholine-induced hepatoma. The role of such substances in the plasma membrane of normal and neoplastic cells]. Malignant hepatomas induced in the rat by N-Nitrosomorpholine showed an absence of trisialogangliosides GT1 and, in some cases, also a decrease in disialoganglioside GD1a and monoganglioside GM1. Simultaneously there occurred an increase in a monoganglioside with a short oligosacharide chain GM3. Such deviations in the composition of glycolipids are in accordance with the literary data mentioning, as a general change, the presence of only some glycolipids as a result of a deficient synthesis of the oligosacharide part of their molecule. The differences in the glycolipid composition of the cell membrane as well as their different arrangement have been discussed with respect to some present views concerning the different behaviour of the neoplastic cell surfaces."}
{"id": "PMID:210964", "title": "[Fine structure of the myoblastic myoma].", "content": "A series of 10 myoblastic myomas were examined with the light and electron microscope. Based on electron microscopical examinations, the findings permitted to divide the cases according to their most probable histogenesis in two groups as follows: a) the granular lesions of the appendix and those of the hypophyseal infundibulum most probably originate from nervous tissue; b) the lesions of the skin and the tongue most probably are results of alterations of cell metabolism.", "contents": "[Fine structure of the myoblastic myoma]. A series of 10 myoblastic myomas were examined with the light and electron microscope. Based on electron microscopical examinations, the findings permitted to divide the cases according to their most probable histogenesis in two groups as follows: a) the granular lesions of the appendix and those of the hypophyseal infundibulum most probably originate from nervous tissue; b) the lesions of the skin and the tongue most probably are results of alterations of cell metabolism."}
{"id": "PMID:210966", "title": "Apparent microviscosity of intact and post-lipolysis (\"remnant\") very low density lipoprotein particles.", "content": "The apparent microviscosity of intact rat plasma very low density lipoprotein (VLDL) and post-lipolysis very low density lipoprotein was determined by fluorescence depolarization measurements and flurorescence decay measurements using 1, 6-diphenylhexatriene. Post-lipolysis very low density lipoprotein was prepared in vitro after incubation of the intact lipoprotein with either purified bovine milk lipoprotein lipase or lipoprotein lipase rich (post-heparin) plasma. During lipolysis, an average of 88% of the triglycerides were hydrolyzed, and the lipoprotein became depleted in phospholipids, cholesterol and apolipoprotein C. The apparent microviscosity of the lipoprotein increased by three-fold from 0.63 to 1.88 poise. It is concluded that the compositional changes occurring during lipolysis affect the physical properties of the lipoprotein, as measured here by the fluidity (microviscosity) of the particles.", "contents": "Apparent microviscosity of intact and post-lipolysis (\"remnant\") very low density lipoprotein particles. The apparent microviscosity of intact rat plasma very low density lipoprotein (VLDL) and post-lipolysis very low density lipoprotein was determined by fluorescence depolarization measurements and flurorescence decay measurements using 1, 6-diphenylhexatriene. Post-lipolysis very low density lipoprotein was prepared in vitro after incubation of the intact lipoprotein with either purified bovine milk lipoprotein lipase or lipoprotein lipase rich (post-heparin) plasma. During lipolysis, an average of 88% of the triglycerides were hydrolyzed, and the lipoprotein became depleted in phospholipids, cholesterol and apolipoprotein C. The apparent microviscosity of the lipoprotein increased by three-fold from 0.63 to 1.88 poise. It is concluded that the compositional changes occurring during lipolysis affect the physical properties of the lipoprotein, as measured here by the fluidity (microviscosity) of the particles."}
{"id": "PMID:210967", "title": "Studies on the surface structure of very low density lipo-proteins.", "content": "Very Low Density Lipoproteins (VLDL) were incubated with 5 different pure phospholipases. From the results the following conclusions were drawn. (1) The phospholipids ,re localized in a monomolecular layer on the outside of the VLDL particles. This supports the lipid core model proposed by several groups. (2) A minor fraction of the phospholipids (ranging from 3 to 10%) cannot be degraded by the enzymes and probably have a strong interaction with apoproteins. (3) The average surface pressure of VLDL is probably low, and comparable with a lateral surface pressure of 15 dynes/cm at the air--water interface, as concluded from experiments with two phospholipases A(2). Calculations of the thickness of the surface coat and protein coverage on the basis of this value agree very well with values reported in literature.", "contents": "Studies on the surface structure of very low density lipo-proteins. Very Low Density Lipoproteins (VLDL) were incubated with 5 different pure phospholipases. From the results the following conclusions were drawn. (1) The phospholipids ,re localized in a monomolecular layer on the outside of the VLDL particles. This supports the lipid core model proposed by several groups. (2) A minor fraction of the phospholipids (ranging from 3 to 10%) cannot be degraded by the enzymes and probably have a strong interaction with apoproteins. (3) The average surface pressure of VLDL is probably low, and comparable with a lateral surface pressure of 15 dynes/cm at the air--water interface, as concluded from experiments with two phospholipases A(2). Calculations of the thickness of the surface coat and protein coverage on the basis of this value agree very well with values reported in literature."}
{"id": "PMID:210968", "title": "[Response of an undifferentiated and nullipotential cell line derived from an A/Heston mouse teratocarcinoma to infection with type C ecotropic murine viruses].", "content": "The PCC6 cell line, derived from an A/Heston Mouse Teratocarcinoma, and composed of nullipotential embryonic carcinoma cells (ECC), is completely resistant to infection with type C murine ecotropic viruses. It reacts as other cell lines previously studied which are derived from a 129 Mouse teratocarcinoma and composed of multipotential ECC.", "contents": "[Response of an undifferentiated and nullipotential cell line derived from an A/Heston mouse teratocarcinoma to infection with type C ecotropic murine viruses]. The PCC6 cell line, derived from an A/Heston Mouse Teratocarcinoma, and composed of nullipotential embryonic carcinoma cells (ECC), is completely resistant to infection with type C murine ecotropic viruses. It reacts as other cell lines previously studied which are derived from a 129 Mouse teratocarcinoma and composed of multipotential ECC."}
{"id": "PMID:210969", "title": "[Rare electrophoretic variants of the proteins adenylate kinase 1, phosphoglucomutase 1 and 2, and transferrin (AK1, PGM1, PGM2, Tf) in two populations of French Guiana].", "content": "Two small populations of inner French Guiana were investigated for red cell enzymes and serum proteins. Rare variants were found in four systems (AK1, PGM1, PGM2, Tf). Similarities between some of these variants and those found in other Amerindian populations indicate that these genetic markers may be valuable in studies of Amerindians. A mutation rate has been estimated from the results.", "contents": "[Rare electrophoretic variants of the proteins adenylate kinase 1, phosphoglucomutase 1 and 2, and transferrin (AK1, PGM1, PGM2, Tf) in two populations of French Guiana]. Two small populations of inner French Guiana were investigated for red cell enzymes and serum proteins. Rare variants were found in four systems (AK1, PGM1, PGM2, Tf). Similarities between some of these variants and those found in other Amerindian populations indicate that these genetic markers may be valuable in studies of Amerindians. A mutation rate has been estimated from the results."}
{"id": "PMID:210972", "title": "Lipoproteins and the inhibitory effect of human endothelial cells on platelet function.", "content": "We investigated the effect of plasma low density lipoproteins (LDL), very low density lipoproteins (VLDL), and high density lipoproteins (HDL) on the platelet inhibitory effect of primary cultures of human endothelial cell monolayers (ECM). ECM incubated with lipoprotein-deficient plasma (LDP) for 2 hours at 37 degrees C had an inhibitory effect on ADP- and collagen-induced platelet aggregation and prostaglandin production in platelet-rich plasma similar to that observed when ECM were preincubated with growth medium or plasma. Concentrations of LDL in LDP up to protein concentration of 1600 microgram/ml had an inhibitory effect on the endothelial cells' ability to modulate these platelet reactions. VLDL at the highest concentration (1600 microgram/ml) had a slightly inhibitory effect, whereas HDL showed no such effect. The inhibitory effect of LDL was not observed during the first hour of incubation. When HDL in concentrations similar to or higher than LDL were combined with LDL, the inhibitory effect of LDL was partially reduced. VLDL combined with LDL or HDL did not interfere with the effects of the later fractions. The inhibitory effect of LDL was significantly reduced when LDL were diluted in whole plasma. Prostacyclin which is synthesized and released from the endothelial cells and contributes to the inhibitory effect upon platelets did not change its effect on platelet reactivity by preincubation with the various lipoprotein fractions. The current studies may indicate that LDL have a direct effect on the endothelial cells and that this effect may be partially counteracted by HDL. This effect of LDL on the endothelial cells reduces the endothelium's ability to inhibit platelet aggregation and thus could favor the tendency to thrombus formation.", "contents": "Lipoproteins and the inhibitory effect of human endothelial cells on platelet function. We investigated the effect of plasma low density lipoproteins (LDL), very low density lipoproteins (VLDL), and high density lipoproteins (HDL) on the platelet inhibitory effect of primary cultures of human endothelial cell monolayers (ECM). ECM incubated with lipoprotein-deficient plasma (LDP) for 2 hours at 37 degrees C had an inhibitory effect on ADP- and collagen-induced platelet aggregation and prostaglandin production in platelet-rich plasma similar to that observed when ECM were preincubated with growth medium or plasma. Concentrations of LDL in LDP up to protein concentration of 1600 microgram/ml had an inhibitory effect on the endothelial cells' ability to modulate these platelet reactions. VLDL at the highest concentration (1600 microgram/ml) had a slightly inhibitory effect, whereas HDL showed no such effect. The inhibitory effect of LDL was not observed during the first hour of incubation. When HDL in concentrations similar to or higher than LDL were combined with LDL, the inhibitory effect of LDL was partially reduced. VLDL combined with LDL or HDL did not interfere with the effects of the later fractions. The inhibitory effect of LDL was significantly reduced when LDL were diluted in whole plasma. Prostacyclin which is synthesized and released from the endothelial cells and contributes to the inhibitory effect upon platelets did not change its effect on platelet reactivity by preincubation with the various lipoprotein fractions. The current studies may indicate that LDL have a direct effect on the endothelial cells and that this effect may be partially counteracted by HDL. This effect of LDL on the endothelial cells reduces the endothelium's ability to inhibit platelet aggregation and thus could favor the tendency to thrombus formation."}
{"id": "PMID:210973", "title": "Role of the peripheral vasculature in changes in venous return caused by isoproterenol, norepinephrine, and methoxamine in anesthetized dogs.", "content": "We studied effects on venous return of alpha- and beta-adrenergic agonists in anesthetized dogs. Blood from the superior and inferior venae cavae (venous return) was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant rate. Isoproterenol infused into the ascending aorta or the right atrium increased the venous return and heart rate and decreased systemic blood pressure. The increase in venous return produced by isoproterenol given into the right atrium was not significantly different from that produced by isoproterenol administered into the ascending aorta, although the increase in heart rate was more marked with the latter route of administration. Norepinephrine infused into the ascending aorta increased the systemic blood pressure, venous return, and heart rate. Methoxamine infused into the ascending aorta increased the systemic blood pressure and decreased the venous return but produced no change in heart rate. Isoproterenol increased the venous return even when the sinoaortic baroreceptor reflex was eliminated. Propranolol abolished the increase in venous return caused by isoproterenol and reversed the increase in venous return caused by norepinephrine. The results suggest that a decrease in venous resistance mediated through a beta-adrenergic mechanism is important in increasing venous return, whereas an increase in venous resistance mediated through an alpha-adrenergic mechanism is responsible for a decrease in venous return.", "contents": "Role of the peripheral vasculature in changes in venous return caused by isoproterenol, norepinephrine, and methoxamine in anesthetized dogs. We studied effects on venous return of alpha- and beta-adrenergic agonists in anesthetized dogs. Blood from the superior and inferior venae cavae (venous return) was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant rate. Isoproterenol infused into the ascending aorta or the right atrium increased the venous return and heart rate and decreased systemic blood pressure. The increase in venous return produced by isoproterenol given into the right atrium was not significantly different from that produced by isoproterenol administered into the ascending aorta, although the increase in heart rate was more marked with the latter route of administration. Norepinephrine infused into the ascending aorta increased the systemic blood pressure, venous return, and heart rate. Methoxamine infused into the ascending aorta increased the systemic blood pressure and decreased the venous return but produced no change in heart rate. Isoproterenol increased the venous return even when the sinoaortic baroreceptor reflex was eliminated. Propranolol abolished the increase in venous return caused by isoproterenol and reversed the increase in venous return caused by norepinephrine. The results suggest that a decrease in venous resistance mediated through a beta-adrenergic mechanism is important in increasing venous return, whereas an increase in venous resistance mediated through an alpha-adrenergic mechanism is responsible for a decrease in venous return."}
{"id": "PMID:210977", "title": "Antagonistic effects of theophylline and adenosine on adrenergic neuroeffector transmission in the rabbit kidney.", "content": "The actions of adenosine and theophylline on adrenergic neuroeffector transmission were studied in the rabbit kidney perfused with Tyrode's solution in which the norepinephrine stores had been labeled with (-)-norepinephrine[3H] ((-)-NE[3H]). We found that adenosine inhibited (-)-NE[3H] release induced by nerve stimulation, increased basal perfusion pressure, and enhanced the vasoconstrictor response to nerve stimulation and norepinephrine in a dose-dependent manner. Theophylline per se had effects on neuroeffector transmission opposite to those of adenosine. All effects of adenosine were antagonized effectively or annulled by theophylline in concentrations having little or no effect on rabbit kidney phosphodiesterase activities. Two other compounds, Ro 20-1724 and ZK 62.711, being equally potent or more potent than theophylline as phosphodiesterase inhibitors, failed to antagonize adenosine-mediated inhibition of (-)-NE[3H] release by nerve stimulation. Ro 20-1724 in high concentration (10(-4) M) inhibited the vasoconstrictor response to nerve stimulation, but it had little additional effect on the enhancement by adenosine. These findings suggest that theophylline specifically antagonizes the effects of adenosine on pre- and postjunctional transmission in the kidney. The results also are consistent with the view that endogenous adenosine may play a role as modulator of adrenergic neuroeffector transmission.", "contents": "Antagonistic effects of theophylline and adenosine on adrenergic neuroeffector transmission in the rabbit kidney. The actions of adenosine and theophylline on adrenergic neuroeffector transmission were studied in the rabbit kidney perfused with Tyrode's solution in which the norepinephrine stores had been labeled with (-)-norepinephrine[3H] ((-)-NE[3H]). We found that adenosine inhibited (-)-NE[3H] release induced by nerve stimulation, increased basal perfusion pressure, and enhanced the vasoconstrictor response to nerve stimulation and norepinephrine in a dose-dependent manner. Theophylline per se had effects on neuroeffector transmission opposite to those of adenosine. All effects of adenosine were antagonized effectively or annulled by theophylline in concentrations having little or no effect on rabbit kidney phosphodiesterase activities. Two other compounds, Ro 20-1724 and ZK 62.711, being equally potent or more potent than theophylline as phosphodiesterase inhibitors, failed to antagonize adenosine-mediated inhibition of (-)-NE[3H] release by nerve stimulation. Ro 20-1724 in high concentration (10(-4) M) inhibited the vasoconstrictor response to nerve stimulation, but it had little additional effect on the enhancement by adenosine. These findings suggest that theophylline specifically antagonizes the effects of adenosine on pre- and postjunctional transmission in the kidney. The results also are consistent with the view that endogenous adenosine may play a role as modulator of adrenergic neuroeffector transmission."}
{"id": "PMID:210981", "title": "Simultaneous determination of serum cholesterol in high- and low-density lipoproteins with use of heparin, Ca2+, and an anion-exchange resin.", "content": "Cholesterol concentrations in serum high-density and low-density lipoproteins are simultaneously determined simply, specifically, and rapidly by use of the precipitation method with heparin, Ca2+, and an anion-exchange resin. The isolation of lipoproteins is reproducible, selective, and complete, as judged by electrophoresis on polyacrylamide gel and by immunoelectrophoresis, with use of samples with very-low-density lipoprotein triglyceride concentrations of less than 3.5 g/liter. The precision of the present method is as good (CV, 2.8-3.1%) as that for the method used by the U.S. Lipid Research Clinics (CV 2.0-3.2%). The present method and the heparin-Mn2+ method of the Clinics gave results that agreed reasonably well (for low-density-lipoprotein cholesterol r = 0.935, P less than 0.001; for high-density-lipoprotein cholesterol r = 0.837, P less than 0.001). we also describe the relations between high- or low-density lipoprotein cholesterol and total cholesterol, and between cholesterol concentrations in these two lipoprotein classes.", "contents": "Simultaneous determination of serum cholesterol in high- and low-density lipoproteins with use of heparin, Ca2+, and an anion-exchange resin. Cholesterol concentrations in serum high-density and low-density lipoproteins are simultaneously determined simply, specifically, and rapidly by use of the precipitation method with heparin, Ca2+, and an anion-exchange resin. The isolation of lipoproteins is reproducible, selective, and complete, as judged by electrophoresis on polyacrylamide gel and by immunoelectrophoresis, with use of samples with very-low-density lipoprotein triglyceride concentrations of less than 3.5 g/liter. The precision of the present method is as good (CV, 2.8-3.1%) as that for the method used by the U.S. Lipid Research Clinics (CV 2.0-3.2%). The present method and the heparin-Mn2+ method of the Clinics gave results that agreed reasonably well (for low-density-lipoprotein cholesterol r = 0.935, P less than 0.001; for high-density-lipoprotein cholesterol r = 0.837, P less than 0.001). we also describe the relations between high- or low-density lipoprotein cholesterol and total cholesterol, and between cholesterol concentrations in these two lipoprotein classes."}
{"id": "PMID:210982", "title": "A fluorogenic substrate for angiotensin-converting enzyme in plasma.", "content": "A simple, sensitive, and reproducible assay for angiotensin-converting enzyme is described. It is based on the hydrolysis of the minimally fluorescent substrate p-nitrobenzyloxycarbonylglycyl-L-tryptophylglycine to the products p-nitrobenzyloxycarbonylglycine and the highly fluorescent L-tryptophylglycine. The L-tryptophylglycine was analyzed by fluorometry (lambda excitation = 285 nm; lambda emission = 350 nm). The mean value for human plasma (serum) is 16.5 nmol of substrate hydrolyzed per minute per milliter of plasma under the described assay conditions.", "contents": "A fluorogenic substrate for angiotensin-converting enzyme in plasma. A simple, sensitive, and reproducible assay for angiotensin-converting enzyme is described. It is based on the hydrolysis of the minimally fluorescent substrate p-nitrobenzyloxycarbonylglycyl-L-tryptophylglycine to the products p-nitrobenzyloxycarbonylglycine and the highly fluorescent L-tryptophylglycine. The L-tryptophylglycine was analyzed by fluorometry (lambda excitation = 285 nm; lambda emission = 350 nm). The mean value for human plasma (serum) is 16.5 nmol of substrate hydrolyzed per minute per milliter of plasma under the described assay conditions."}
{"id": "PMID:210988", "title": "The effects of thiol moiety of levamisole on both cellular and humoral immunity during the early response to a hapten-carrier complex.", "content": "Cell-mediated reactions to the carrier and antibody-mediated reactions to the hapten were studied in guinea-pigs treated with a single i.v. injection of the thiol moiety of levamisole (DTC), before or after immunization with a hapten-carrier complex. The results show that a heavy dose of DTC induced delayed hypersensitivity reactions to the carrier and decreased antibody synthesis to the hapten. On the other hand, with a small dose of DTC no delayed hypersensitivity could be induced, but antibody synthesis to the hapten was depressed or enhanced, depending upon whether the injection was done before or after immunization. The mechanisms whereby DTC modulated the immune response are discussed.", "contents": "The effects of thiol moiety of levamisole on both cellular and humoral immunity during the early response to a hapten-carrier complex. Cell-mediated reactions to the carrier and antibody-mediated reactions to the hapten were studied in guinea-pigs treated with a single i.v. injection of the thiol moiety of levamisole (DTC), before or after immunization with a hapten-carrier complex. The results show that a heavy dose of DTC induced delayed hypersensitivity reactions to the carrier and decreased antibody synthesis to the hapten. On the other hand, with a small dose of DTC no delayed hypersensitivity could be induced, but antibody synthesis to the hapten was depressed or enhanced, depending upon whether the injection was done before or after immunization. The mechanisms whereby DTC modulated the immune response are discussed."}
{"id": "PMID:210989", "title": "Vascular pedicle fibular transplantation as treatment for bone tumor.", "content": "In 4 cases of bone tumor in which extensive bone defects resulted from removal of the tumorous focus, vascular pedicle free fibular transplantation was performed using microsurgical techniques together with filling the defects with iliac bone. Early bone union was achieved. Atrophy and fracture were avoided. Early postoperative physical therapy was possible. The vessels selected in the recipient site are dependent upon the location of the graft bed, but the anastomosed site of the vessels should be kept outside of the graft bed. It is important to plan the operation so as to avoid motion at the site of callus formation and tension at the anastomosis site.", "contents": "Vascular pedicle fibular transplantation as treatment for bone tumor. In 4 cases of bone tumor in which extensive bone defects resulted from removal of the tumorous focus, vascular pedicle free fibular transplantation was performed using microsurgical techniques together with filling the defects with iliac bone. Early bone union was achieved. Atrophy and fracture were avoided. Early postoperative physical therapy was possible. The vessels selected in the recipient site are dependent upon the location of the graft bed, but the anastomosed site of the vessels should be kept outside of the graft bed. It is important to plan the operation so as to avoid motion at the site of callus formation and tension at the anastomosis site."}
{"id": "PMID:210990", "title": "Angiotensin-induced variations of receptors in rat uterine membranes.", "content": "1. 3H-labelled angiotensin II specfically binds to plasma membranes of rat uterine smooth muscle cells. Two classes of binding sites differing in their affinity for the hormone were demonstrated. The high-affinity binding sites (KD 29 degrees C approximately 2.0 X 10(-8) mol/l) probably correspond to the receptors involved in the biological response. 2. Bilateral nephrectomy significantly increases the concentration of 3H-labelled angiotensin-binding sites, a phenomenon which seems unrelated to the freeing of receptor sites secondary to the suppression of plasma angiotensin. This phenomenon may be responsible for the specific hypersensitivity in vitro to angiotensin of uteri excised in anephric rats as compared with normal rats. 3. Angiotensin II infusion in nephrectomized rats reduced the concentration of 3H-labelled angiotensin-binding sites. 4. It is suggested that the angiotensin receptor concentration is regulated by the concentration of circulating angiotensin.", "contents": "Angiotensin-induced variations of receptors in rat uterine membranes. 1. 3H-labelled angiotensin II specfically binds to plasma membranes of rat uterine smooth muscle cells. Two classes of binding sites differing in their affinity for the hormone were demonstrated. The high-affinity binding sites (KD 29 degrees C approximately 2.0 X 10(-8) mol/l) probably correspond to the receptors involved in the biological response. 2. Bilateral nephrectomy significantly increases the concentration of 3H-labelled angiotensin-binding sites, a phenomenon which seems unrelated to the freeing of receptor sites secondary to the suppression of plasma angiotensin. This phenomenon may be responsible for the specific hypersensitivity in vitro to angiotensin of uteri excised in anephric rats as compared with normal rats. 3. Angiotensin II infusion in nephrectomized rats reduced the concentration of 3H-labelled angiotensin-binding sites. 4. It is suggested that the angiotensin receptor concentration is regulated by the concentration of circulating angiotensin."}
{"id": "PMID:210991", "title": "Localization of central noradrenergic mechanisms in cardiovascular regulation in rats.", "content": "1. Various drugs were injected stereotactically into the brain of anaesthetized rats. 2. Noradrenaline injected into the area of the nucleus of the tractus solitarius in the lower brain stem or into the far anterior hypothalamus/pre-optic region induced a fall in blood pressure and heart rate related to the administered dose. 3. When injected into the anterior hypothalamus/pre-optic region, clonidine and alpha-methylnoradrenaline induced a long-lasting decrease in blood pressure and heart rate.", "contents": "Localization of central noradrenergic mechanisms in cardiovascular regulation in rats. 1. Various drugs were injected stereotactically into the brain of anaesthetized rats. 2. Noradrenaline injected into the area of the nucleus of the tractus solitarius in the lower brain stem or into the far anterior hypothalamus/pre-optic region induced a fall in blood pressure and heart rate related to the administered dose. 3. When injected into the anterior hypothalamus/pre-optic region, clonidine and alpha-methylnoradrenaline induced a long-lasting decrease in blood pressure and heart rate."}
{"id": "PMID:210992", "title": "Phagocytosis: a review.", "content": "Primitive unicellular organisms depend greatly on internalization of particulate matter for nourishment. In metazoa, this process is further developed to play a major role in mechanisms of defense. This review analyzes, mainly in mammalian systems, the various phenomena surrounding the phagocytic act. Much of the emphasis is placed on experimental work which has recently elucidated some of its features. Both the structural and functional aspects of phagocytosis are considered throughout the review, which is subdivided into an examination of chemotaxis and the various agents inducing it, the mode of recognition of particles to be phagocytized, and the mechanisms of ingestion. The last includes a discussion of the possible means whereby recognition is translated into ingestion, the modes of adhesion of particles onto the surface of phagocytes, the formation and fusion of pseudopodia during engulfment and ingestion, and process and significance of degranulation. In addition, the metabolic changes in phagocytes during the processes of chemotaxis, ingestion, and digestion are described. A discussion of the various ways phagocytes may destroy microorganisms incorporates an appreciation of the importance of the microbicidal action of the acidic environment of the phagosome, the various lysosomal contents, hydrogen peroxide, superoxide, singlet oxygen, and chemiluminescence. The interdependence and interrelationship of the induction and cooperation of these mechanisms are examined.", "contents": "Phagocytosis: a review. Primitive unicellular organisms depend greatly on internalization of particulate matter for nourishment. In metazoa, this process is further developed to play a major role in mechanisms of defense. This review analyzes, mainly in mammalian systems, the various phenomena surrounding the phagocytic act. Much of the emphasis is placed on experimental work which has recently elucidated some of its features. Both the structural and functional aspects of phagocytosis are considered throughout the review, which is subdivided into an examination of chemotaxis and the various agents inducing it, the mode of recognition of particles to be phagocytized, and the mechanisms of ingestion. The last includes a discussion of the possible means whereby recognition is translated into ingestion, the modes of adhesion of particles onto the surface of phagocytes, the formation and fusion of pseudopodia during engulfment and ingestion, and process and significance of degranulation. In addition, the metabolic changes in phagocytes during the processes of chemotaxis, ingestion, and digestion are described. A discussion of the various ways phagocytes may destroy microorganisms incorporates an appreciation of the importance of the microbicidal action of the acidic environment of the phagosome, the various lysosomal contents, hydrogen peroxide, superoxide, singlet oxygen, and chemiluminescence. The interdependence and interrelationship of the induction and cooperation of these mechanisms are examined."}
{"id": "PMID:210993", "title": "Active chloride transport powered by Na-K-ATPase in shark rectal gland.", "content": "The isolated rectal gland of the spiny dogfish is a unique model for the study of active chloride transport. The gland is stimulated to secrete chloride agains an electrical and a chemical gradient when perfused in vitro by theophylline and/or dibutyryl cyclic AMP. Chloride secretion is depressed by ouabain which inhibits Na-K-ATPase. Thiocyanate and furosemide also inhibit chloride secretion but ethoxolamide, a carbonic anhydrase inhibitor, does not. Chloride transport is highly dependent on sodium concentration in the perfusate. The intracellular concentration of chloride in intact glands exceeds the level expected at electrochemical equilibrium, suggesting active transport of chloride into the cell. These features suggest a general hypothesis for chloride secretion in which the uphill transport of chloride into the cytoplasm is coupled through a membrane carrier to the downhill movement of sodium along its electrochemical gradient. The latter is maintained by the Na-K-ATPase pump while chloride is extruded into the duct by electrical forces.", "contents": "Active chloride transport powered by Na-K-ATPase in shark rectal gland. The isolated rectal gland of the spiny dogfish is a unique model for the study of active chloride transport. The gland is stimulated to secrete chloride agains an electrical and a chemical gradient when perfused in vitro by theophylline and/or dibutyryl cyclic AMP. Chloride secretion is depressed by ouabain which inhibits Na-K-ATPase. Thiocyanate and furosemide also inhibit chloride secretion but ethoxolamide, a carbonic anhydrase inhibitor, does not. Chloride transport is highly dependent on sodium concentration in the perfusate. The intracellular concentration of chloride in intact glands exceeds the level expected at electrochemical equilibrium, suggesting active transport of chloride into the cell. These features suggest a general hypothesis for chloride secretion in which the uphill transport of chloride into the cytoplasm is coupled through a membrane carrier to the downhill movement of sodium along its electrochemical gradient. The latter is maintained by the Na-K-ATPase pump while chloride is extruded into the duct by electrical forces."}
{"id": "PMID:210994", "title": "Structure and function of the Na, K-ion pump or Na, K-ATPase in mammalian kidney.", "content": "Information about the purified Na, K-ATPase from the mammalian thick ascending limb of Henle is related to studies on its localization in tubular cells and the environment along the transport pathways to reach a better understanding of the role of this pump in the active transtubular transport of Na+.", "contents": "Structure and function of the Na, K-ion pump or Na, K-ATPase in mammalian kidney. Information about the purified Na, K-ATPase from the mammalian thick ascending limb of Henle is related to studies on its localization in tubular cells and the environment along the transport pathways to reach a better understanding of the role of this pump in the active transtubular transport of Na+."}
{"id": "PMID:210995", "title": "Inhibition of (Na+K+)-ATPase and cation transport by an antibody against renal plasma membranes.", "content": "An antibody was raised in rabbits against NaI extracted plasma membranes of rat kidney. The antibody inhibited (Na+K+)-ATPase of basolateral membranes and of rat erythrocyte ghosts. Also K+-stimulated pNPase was inhibited. No effect on Mg-ATPase and basal pNPase activity was registered. Kinetic experiments with Na+,K+ and Mg-ATP showed a noncompetitive inhibition of (Na+K+)-ATPase by the antibody. Hill constants were unchanged. In renal epithelial cell cultures as well as in intact rat erythrocytes ouabain sensitive 22Na-efflux and 42K influx was inhibited by the antibody. It is concluded that outward facing Na+K+-ATPase is immunogenic. The antibody can be raised when the antigen is adequately disintegrated to open otherwise hidden antigenic sites.", "contents": "Inhibition of (Na+K+)-ATPase and cation transport by an antibody against renal plasma membranes. An antibody was raised in rabbits against NaI extracted plasma membranes of rat kidney. The antibody inhibited (Na+K+)-ATPase of basolateral membranes and of rat erythrocyte ghosts. Also K+-stimulated pNPase was inhibited. No effect on Mg-ATPase and basal pNPase activity was registered. Kinetic experiments with Na+,K+ and Mg-ATP showed a noncompetitive inhibition of (Na+K+)-ATPase by the antibody. Hill constants were unchanged. In renal epithelial cell cultures as well as in intact rat erythrocytes ouabain sensitive 22Na-efflux and 42K influx was inhibited by the antibody. It is concluded that outward facing Na+K+-ATPase is immunogenic. The antibody can be raised when the antigen is adequately disintegrated to open otherwise hidden antigenic sites."}
{"id": "PMID:210996", "title": "Carbohydrate metabolism in rat kidney: heterogeneous distribution of glycolytic and gluconeogenic key enzymes.", "content": "The distribution pattern of the unidirectional enzymes of gluconeogenesis and glycolysis, fructose-1,6-bisphosphatase (EC 3.1.3.11) and phosphofructokinase (EC 2.7.1.11), within the nephron was studied by the microdissection and oil-well techniques according to LOWRY and PASSONNEAU [11]. Fructose-1,6-bisphosphatase activity was found to be highest in the proximal convolution, whereas phosphofructokinase revealed its highest activity in the thick ascending limb of Henle's loop. Starvation and NH4Cl acidosis led to an increase of fructose-1,6-bisphosphatase activity in the proximal convolution. These results indicate a clear separation of the glucose synthesizing and degrading pathways within the nephron, which is maintained in conditions that stimulate gluconeogenesis.", "contents": "Carbohydrate metabolism in rat kidney: heterogeneous distribution of glycolytic and gluconeogenic key enzymes. The distribution pattern of the unidirectional enzymes of gluconeogenesis and glycolysis, fructose-1,6-bisphosphatase (EC 3.1.3.11) and phosphofructokinase (EC 2.7.1.11), within the nephron was studied by the microdissection and oil-well techniques according to LOWRY and PASSONNEAU [11]. Fructose-1,6-bisphosphatase activity was found to be highest in the proximal convolution, whereas phosphofructokinase revealed its highest activity in the thick ascending limb of Henle's loop. Starvation and NH4Cl acidosis led to an increase of fructose-1,6-bisphosphatase activity in the proximal convolution. These results indicate a clear separation of the glucose synthesizing and degrading pathways within the nephron, which is maintained in conditions that stimulate gluconeogenesis."}
{"id": "PMID:210997", "title": "Gluconeogenic enzymes in defined structures of developing rat nephron.", "content": "Three gluconeogenic enzymes, P-pyruvate carboxykinase (PPCK), fructose-1-6 bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase) were measured in identified structures of rat nephron from 2 days before birth to maturity. In the proximal convoluted tubule, the three enzymes increased from the earliest age assayed to +14 days (PPCK, 7-fold, FBPase, 2-fold and G6Pase, 50-fold). Among the 7 defined structures that were analyzed, highest levels at all ages were in the proximal convoluted tubule with almost no activity in the distal convoluted tubule. All three enzymes had negligible activity in the neogenic zone and mesenchyme. Supported by grants from the Public Health Service (HD 03891 and NS-05221) and the American Cancer Society (P-78).", "contents": "Gluconeogenic enzymes in defined structures of developing rat nephron. Three gluconeogenic enzymes, P-pyruvate carboxykinase (PPCK), fructose-1-6 bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase) were measured in identified structures of rat nephron from 2 days before birth to maturity. In the proximal convoluted tubule, the three enzymes increased from the earliest age assayed to +14 days (PPCK, 7-fold, FBPase, 2-fold and G6Pase, 50-fold). Among the 7 defined structures that were analyzed, highest levels at all ages were in the proximal convoluted tubule with almost no activity in the distal convoluted tubule. All three enzymes had negligible activity in the neogenic zone and mesenchyme. Supported by grants from the Public Health Service (HD 03891 and NS-05221) and the American Cancer Society (P-78)."}
{"id": "PMID:210998", "title": "Induction of rat kidney gluconeogenic ability after impairment of liver gluconeogenesis.", "content": "The renal gluconeogenic response to the inhibition of liver gluconeogenesis was studied in rats treated with CCl4. This treatment resulted in a generalized fall of hepatic gluconeogenic enzyme activities and a complete impairment of liver gluconeogenesis. On the contrary, an enhancement of renal phosphoenolpyruvate carboxykinase activity and gluconeogenic ability was found. This stimulation seemed to be not related to metabolic acidosis but mediated by glucocorticoids. On the other hand, the pattern of intermediate metabolites in kidney suggested that renal gluconeogenesis was operative in these conditions, probably playing a key role in glucose homeostasis.", "contents": "Induction of rat kidney gluconeogenic ability after impairment of liver gluconeogenesis. The renal gluconeogenic response to the inhibition of liver gluconeogenesis was studied in rats treated with CCl4. This treatment resulted in a generalized fall of hepatic gluconeogenic enzyme activities and a complete impairment of liver gluconeogenesis. On the contrary, an enhancement of renal phosphoenolpyruvate carboxykinase activity and gluconeogenic ability was found. This stimulation seemed to be not related to metabolic acidosis but mediated by glucocorticoids. On the other hand, the pattern of intermediate metabolites in kidney suggested that renal gluconeogenesis was operative in these conditions, probably playing a key role in glucose homeostasis."}
{"id": "PMID:210999", "title": "Interaction of rumen development and renal gluconeogenesis in lambs.", "content": "Renal gluconeogenesis of equal aged lambs with different states of rumen development was studied. Going from preruminantto ruminant stage, the rate of glucose formation from several precursors increased. Concomitantly urine pH shifted from acid to base state. Obviously, an enhanced secretion of H+ in lambs kidney during rumen development does not stimulate renal gluconeogenesis. Furthermore, there is no indication from our data that renal gluconeogenesis in lambs is inversely related to the activity of the sodium pump.", "contents": "Interaction of rumen development and renal gluconeogenesis in lambs. Renal gluconeogenesis of equal aged lambs with different states of rumen development was studied. Going from preruminantto ruminant stage, the rate of glucose formation from several precursors increased. Concomitantly urine pH shifted from acid to base state. Obviously, an enhanced secretion of H+ in lambs kidney during rumen development does not stimulate renal gluconeogenesis. Furthermore, there is no indication from our data that renal gluconeogenesis in lambs is inversely related to the activity of the sodium pump."}
{"id": "PMID:211005", "title": "Somatostatin and the endocrine pancreas.", "content": "Thus far, somatostatin has been used primarily as a research tool to investigate pancreatic alpha- and beta- cell function. On the basis of its ability to inhibit insulin and glucagon secretion, several therapeutic applications have been suggested: e.g., as an adjunct in the treatment of diabetes mellitus, or as a palliative agent in inoperable islet tumors. Current experiments are underway to develop more specific analogs with longer durations of action to permit clinical evaluation of these potential applications. The presence of somatostatin within the pancreatic D cells raises the possibility that it may function as a local regulator of insulin and glucagon release. Clearly, further work is needed to delineate the factors governing the secretion of somatostatin and its mode of action. Such studies may uncover a new class of syndromes resulting from D-cell dysfunction.", "contents": "Somatostatin and the endocrine pancreas. Thus far, somatostatin has been used primarily as a research tool to investigate pancreatic alpha- and beta- cell function. On the basis of its ability to inhibit insulin and glucagon secretion, several therapeutic applications have been suggested: e.g., as an adjunct in the treatment of diabetes mellitus, or as a palliative agent in inoperable islet tumors. Current experiments are underway to develop more specific analogs with longer durations of action to permit clinical evaluation of these potential applications. The presence of somatostatin within the pancreatic D cells raises the possibility that it may function as a local regulator of insulin and glucagon release. Clearly, further work is needed to delineate the factors governing the secretion of somatostatin and its mode of action. Such studies may uncover a new class of syndromes resulting from D-cell dysfunction."}
{"id": "PMID:211000", "title": "The effect of parathyroid hormone (PTH) and dietary phosphate on the sodium-dependent phosphate transport system located in the rat renal brush border membrane.", "content": "The effect of two parameters regulating renal phosphate excretion, namely parathyroid hormone application and dietary phosphate intake, on the transport properties of isolated rat renal brush border membrane vesicles was investigated. In the first set of experiments brush border membrane vesicles from young normal rats injected i.m. with 30 USP parathyroid hormone or i.v. with 1 mg dibutyryl cAMP were compared. PTH and dbcAMP injection decreased specifically the Vmax of the sodium-dependent phosphate transport system by appr. 30%. In a second set of experiments rats were kept on phosphate-rich and phosphate-poor diet and after 6-8 weeks the brush border membranes were isolated. The membranes obtained from phosphate-depleted animals showed a markedly (approximately 100%) higher initial sodium-dependent phosphate uptake than membranes isolated from animals kept on phosphate-rich diet. Again only the sodium-dependent phosphate uptake was affected, sodium-independent phosphate permeability, sodium-dependent D-glucose transport, mannitol permeability and sodium permeability remained unchanged.", "contents": "The effect of parathyroid hormone (PTH) and dietary phosphate on the sodium-dependent phosphate transport system located in the rat renal brush border membrane. The effect of two parameters regulating renal phosphate excretion, namely parathyroid hormone application and dietary phosphate intake, on the transport properties of isolated rat renal brush border membrane vesicles was investigated. In the first set of experiments brush border membrane vesicles from young normal rats injected i.m. with 30 USP parathyroid hormone or i.v. with 1 mg dibutyryl cAMP were compared. PTH and dbcAMP injection decreased specifically the Vmax of the sodium-dependent phosphate transport system by appr. 30%. In a second set of experiments rats were kept on phosphate-rich and phosphate-poor diet and after 6-8 weeks the brush border membranes were isolated. The membranes obtained from phosphate-depleted animals showed a markedly (approximately 100%) higher initial sodium-dependent phosphate uptake than membranes isolated from animals kept on phosphate-rich diet. Again only the sodium-dependent phosphate uptake was affected, sodium-independent phosphate permeability, sodium-dependent D-glucose transport, mannitol permeability and sodium permeability remained unchanged."}
{"id": "PMID:211010", "title": "Tissue culture of human breast tumours.", "content": "Several media have been used in an attempt to assess the most appropriate combination of ingredients to effect good cell growth from human breast tumours. Good epithelial cell growth has been obtained in 60 out of a group of 160 tumours successfully cultured in four types of basic media. The other tumours were fibroblastic in nature or contained a mixture of epithelial and fibroblastic cells.", "contents": "Tissue culture of human breast tumours. Several media have been used in an attempt to assess the most appropriate combination of ingredients to effect good cell growth from human breast tumours. Good epithelial cell growth has been obtained in 60 out of a group of 160 tumours successfully cultured in four types of basic media. The other tumours were fibroblastic in nature or contained a mixture of epithelial and fibroblastic cells."}
{"id": "PMID:211013", "title": "Possible role of infectious simian foamy virus DNA in persistent infection.", "content": "Simian foamy virus type 7 (SFV-7) can persist in peripheral blood leukocytes of SFV-7-infected rabbits. Rabbit peripheral blood leukoyctes cultured in vitro did not support the growth of SFV-7, but low titer of virus could be detected after 4 to 5 days incubation. The DNA derived from SFV-7 infected primary rabbit kidney cells is infectious. The presence of SFV-7 DNA provirus in infected rabbit kidney cells during replication may contribute one of the mechanisms of persistance.", "contents": "Possible role of infectious simian foamy virus DNA in persistent infection. Simian foamy virus type 7 (SFV-7) can persist in peripheral blood leukocytes of SFV-7-infected rabbits. Rabbit peripheral blood leukoyctes cultured in vitro did not support the growth of SFV-7, but low titer of virus could be detected after 4 to 5 days incubation. The DNA derived from SFV-7 infected primary rabbit kidney cells is infectious. The presence of SFV-7 DNA provirus in infected rabbit kidney cells during replication may contribute one of the mechanisms of persistance."}
{"id": "PMID:211014", "title": "Infection of Taiwan monkey T and B cells with Epstein-Barr virus.", "content": "In order to establish Taiwan monkey lymphoblastoid cell lines, attempts were made to raise the susceptibility of monkey lymphocytes to Epstein-Barr virus (EBV) by chemical and enzymatic treatments. EBV infectivity to monkey T and B cells were tested by detection of EBV early antigens in infected cells with the indirect immunofluorescent antibody technique. Treatments of monkey unfractionated lymphocytes with DEAE-Dextran (160 microgram/ml) for 1 hr, ethylenediamine tetra-acetic acid (EDTA, 0.5%) for 10 min, 5-bromodeoxyuridine (BUdR, 12.5 microgram/ml) for 23 hr and 5-iodo-2'-deoxyuridine (IUdR, 12.5 microgram/ml) for 20 hr raised the susceptibility of the cells to EBV. However, trypsin treatment (0.05, 0.1 and 0.2%) at 37 degrees C for 5 min did not affect cell susceptibility to EBV. Unfractionated lymphocytes, T cells which were purified by rosette formation with sheep red blood cells, and a B cell-rich population obtained by the treatment of lymphocytes with antithymoycte serum were treated with the chemicals described above. The results showed that although the possibility of T cell susceptibility to EBV could not be ruled out because of 1 to 2.5% of B cell contamination in purified T cells, the main target cells in Taiwan monkey leukocytes for EBV infection were B cells.", "contents": "Infection of Taiwan monkey T and B cells with Epstein-Barr virus. In order to establish Taiwan monkey lymphoblastoid cell lines, attempts were made to raise the susceptibility of monkey lymphocytes to Epstein-Barr virus (EBV) by chemical and enzymatic treatments. EBV infectivity to monkey T and B cells were tested by detection of EBV early antigens in infected cells with the indirect immunofluorescent antibody technique. Treatments of monkey unfractionated lymphocytes with DEAE-Dextran (160 microgram/ml) for 1 hr, ethylenediamine tetra-acetic acid (EDTA, 0.5%) for 10 min, 5-bromodeoxyuridine (BUdR, 12.5 microgram/ml) for 23 hr and 5-iodo-2'-deoxyuridine (IUdR, 12.5 microgram/ml) for 20 hr raised the susceptibility of the cells to EBV. However, trypsin treatment (0.05, 0.1 and 0.2%) at 37 degrees C for 5 min did not affect cell susceptibility to EBV. Unfractionated lymphocytes, T cells which were purified by rosette formation with sheep red blood cells, and a B cell-rich population obtained by the treatment of lymphocytes with antithymoycte serum were treated with the chemicals described above. The results showed that although the possibility of T cell susceptibility to EBV could not be ruled out because of 1 to 2.5% of B cell contamination in purified T cells, the main target cells in Taiwan monkey leukocytes for EBV infection were B cells."}
{"id": "PMID:211015", "title": "IgG and IgA antibodies to Epstein-Barr virus in nasopharyngeal carcinoma patients.", "content": "Immunoglobulin levels and IgG and IgA antibodies to Epstein-Barr virus (EBV), viral capsid antigens (VCA) and early antigens (EA) were tested in 67 untreated (5 stage I, 32 stage II, 16 stage III and 14 stage IV), 21 treated and 7 recurrent nasopharyngeal carcinoma (NPC) patients and 54 normal subjects. The mean serum concentrations of IgG, IgA and IgM in NPC patients were higher than those of the normal control. 41.1, 86.3, 94.7 and 95.8% of NPC patients had anti-VCA titers of greater than or equal to 1:640 and greater than or equal to 1:40 in IgG and IgA, and anti-EA titers of greater than or equal to 1:40 and greater than or equal to 1:10 in IgG and IgA, respectively. But none of the control had such titers. IgG and IgA levels, anti-VCA titers in IgG and IgA, and anti-EA titers in IgG increased with advances of the disease in untreated NPC patients. Untreated patients had higher anti-VCA titers in IgG,  and anti-EA titers in IgG and IgA than 60Co-treated cases, but lower than recurrent patients. Anti-VCA in IgA and IgG was more closely correlated than anti-EA in IgA and IgG. Anti-VCA and anti-EA antibodies in IgA were detected from the throat washing of a NPC patient at clinical stage III.", "contents": "IgG and IgA antibodies to Epstein-Barr virus in nasopharyngeal carcinoma patients. Immunoglobulin levels and IgG and IgA antibodies to Epstein-Barr virus (EBV), viral capsid antigens (VCA) and early antigens (EA) were tested in 67 untreated (5 stage I, 32 stage II, 16 stage III and 14 stage IV), 21 treated and 7 recurrent nasopharyngeal carcinoma (NPC) patients and 54 normal subjects. The mean serum concentrations of IgG, IgA and IgM in NPC patients were higher than those of the normal control. 41.1, 86.3, 94.7 and 95.8% of NPC patients had anti-VCA titers of greater than or equal to 1:640 and greater than or equal to 1:40 in IgG and IgA, and anti-EA titers of greater than or equal to 1:40 and greater than or equal to 1:10 in IgG and IgA, respectively. But none of the control had such titers. IgG and IgA levels, anti-VCA titers in IgG and IgA, and anti-EA titers in IgG increased with advances of the disease in untreated NPC patients. Untreated patients had higher anti-VCA titers in IgG,  and anti-EA titers in IgG and IgA than 60Co-treated cases, but lower than recurrent patients. Anti-VCA in IgA and IgG was more closely correlated than anti-EA in IgA and IgG. Anti-VCA and anti-EA antibodies in IgA were detected from the throat washing of a NPC patient at clinical stage III."}
{"id": "PMID:211017", "title": "The organic chemistry of phosphate transfer.", "content": "Studies in simple systems have identified the reaction mechanisms likely to be involved in biological phosphate transfer and provide the background for understanding the reaction in vivo. Metabolic pathways start from inorganic phosphate, but the introduction of organophosphorus compounds allows us to by-pass early steps and modify specific enzyme-catalyzed reactions. In some cases, as with the nerve poisons, the effects are not specific to enzymes catalyzing reactions of organophosphorus compounds. But the success of any rational chemical intervention depends on both our understanding of the biochemical reaction and the current state of synthetic organophosphorus chemistry. The chemistry of the phosphate transfer process in cases where chemical intervention in metabolic processes has been successful is summarized, and some less familiar types of organophosphorus compound are discussed in the light of the apparent requirements for successful intervention.", "contents": "The organic chemistry of phosphate transfer. Studies in simple systems have identified the reaction mechanisms likely to be involved in biological phosphate transfer and provide the background for understanding the reaction in vivo. Metabolic pathways start from inorganic phosphate, but the introduction of organophosphorus compounds allows us to by-pass early steps and modify specific enzyme-catalyzed reactions. In some cases, as with the nerve poisons, the effects are not specific to enzymes catalyzing reactions of organophosphorus compounds. But the success of any rational chemical intervention depends on both our understanding of the biochemical reaction and the current state of synthetic organophosphorus chemistry. The chemistry of the phosphate transfer process in cases where chemical intervention in metabolic processes has been successful is summarized, and some less familiar types of organophosphorus compound are discussed in the light of the apparent requirements for successful intervention."}
{"id": "PMID:211024", "title": "Studies on the mechanism of action of ACTH on triglyceride synthesis in fat cells.", "content": "It was found that ACTH greatly reduced lipogenesis in fat cells in the presence of calcium ion, but not in the absence of calcium ion. Of the enzymes involved in triglyceride synthesis from fatty acid in lipid micelle membranes, only acyl-CoA synthetase was inhibited by calcium ion, the apparent Ki value of calcium ion being 4.2 X 10(-4) M. The Km values of the enzyme for palmitate and ATP were 2.0 X 10(-4) M and 2.5 X 10(-4) M, respectively and calcium ion caused non-competitive inhibition with both palmitate and ATP. The acyl-CoA synthetase activity of lipid micelle membranes was inhibited by treatment with phospholipase A or C, but not by treatment with phospholipase D. The mechanism of inhibition of triglyceride synthesis by ACTH is discussed on the basis of these results.", "contents": "Studies on the mechanism of action of ACTH on triglyceride synthesis in fat cells. It was found that ACTH greatly reduced lipogenesis in fat cells in the presence of calcium ion, but not in the absence of calcium ion. Of the enzymes involved in triglyceride synthesis from fatty acid in lipid micelle membranes, only acyl-CoA synthetase was inhibited by calcium ion, the apparent Ki value of calcium ion being 4.2 X 10(-4) M. The Km values of the enzyme for palmitate and ATP were 2.0 X 10(-4) M and 2.5 X 10(-4) M, respectively and calcium ion caused non-competitive inhibition with both palmitate and ATP. The acyl-CoA synthetase activity of lipid micelle membranes was inhibited by treatment with phospholipase A or C, but not by treatment with phospholipase D. The mechanism of inhibition of triglyceride synthesis by ACTH is discussed on the basis of these results."}
{"id": "PMID:211025", "title": "Plasma levels of 18-hydroxy-11-deoxycorticosterone in essential hypertension.", "content": "In order to investigate the role of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) in essential hypertension (EH), the responses of plasma 17-OH-DOC to 7 stimulation tests (furosemide test, adrenal suppression test, angiotensin II infusion test, adrenal stimulation test, metopirone test, saline infusion test and potassium chloride infusion test) and the circadian rhythm were investigated in 18 patients with essential hypertension (low renin group: 8, and normal renin group: 10). From the present study, it micht be thought that plasma 18-OH-DOC does not play an important role in the suppression of PRA in patients with low PRA.", "contents": "Plasma levels of 18-hydroxy-11-deoxycorticosterone in essential hypertension. In order to investigate the role of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) in essential hypertension (EH), the responses of plasma 17-OH-DOC to 7 stimulation tests (furosemide test, adrenal suppression test, angiotensin II infusion test, adrenal stimulation test, metopirone test, saline infusion test and potassium chloride infusion test) and the circadian rhythm were investigated in 18 patients with essential hypertension (low renin group: 8, and normal renin group: 10). From the present study, it micht be thought that plasma 18-OH-DOC does not play an important role in the suppression of PRA in patients with low PRA."}
{"id": "PMID:211026", "title": "Effects of sulphydryl reagents on pancreatic glucagon secretion in vitro.", "content": "The effect of sulphydryl reagents on glucagon secretion of isolated Wistar rats islets was studied. Chloromercuribenzene-p-sulphonic acid (CMBS) is a strong stimulator of glucagon secretion, whereas 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) markedly inhibited the hormone release. The effect of CMBS could not be suppressed by 20 mM glucose, but in the presence of 1 mM 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulphonic acid (SITS), and is independent of the glucagon content of islets. The results let us assume that sulphydryl-groups of pancreatic A-cells are involved in the regulation of glucagon secretion.", "contents": "Effects of sulphydryl reagents on pancreatic glucagon secretion in vitro. The effect of sulphydryl reagents on glucagon secretion of isolated Wistar rats islets was studied. Chloromercuribenzene-p-sulphonic acid (CMBS) is a strong stimulator of glucagon secretion, whereas 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) markedly inhibited the hormone release. The effect of CMBS could not be suppressed by 20 mM glucose, but in the presence of 1 mM 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulphonic acid (SITS), and is independent of the glucagon content of islets. The results let us assume that sulphydryl-groups of pancreatic A-cells are involved in the regulation of glucagon secretion."}
{"id": "PMID:211028", "title": "Diminished sensitivity of re-initiation of translation to inhibition by cap analogues in reticulocyte lysates.", "content": "In a nuclease-treated reticuloyte lysate reinitiation of protein biosynthesis was less inhibited by 7-methylguanosine 5'-monophosphate (m7GMP), whereas primary-initiation could be totally blocked by cap analogues. We suggest that a cap binding factor binds to mRNA as a first step in initiation of protein synthesis and that this factor remains bound during the subsequent reinitiation cycles. Primarily because of the greater relative importance of the reinitiation process, globin synthesis in the untreated lysate was less inhibited by m7GMP.", "contents": "Diminished sensitivity of re-initiation of translation to inhibition by cap analogues in reticulocyte lysates. In a nuclease-treated reticuloyte lysate reinitiation of protein biosynthesis was less inhibited by 7-methylguanosine 5'-monophosphate (m7GMP), whereas primary-initiation could be totally blocked by cap analogues. We suggest that a cap binding factor binds to mRNA as a first step in initiation of protein synthesis and that this factor remains bound during the subsequent reinitiation cycles. Primarily because of the greater relative importance of the reinitiation process, globin synthesis in the untreated lysate was less inhibited by m7GMP."}
{"id": "PMID:211029", "title": "Poly(ADP-ribose) polymerase from Ehrlich ascites tumor cells. Properties of the purified polymerase.", "content": "Poly(ADP-ribose) polymerase from Ehrlich ascites tumor cells, partially purified by chromatography on DNA-agarose, was obtained as a more than 80% homogeneous preparation by isoelectric focusing in a sucrose gradient. The polymerase activity was shown to be associated with the major protein in the preparation. Results obtained by electrophoresis in the presence of sodium dodecyl-sulfate indicated that poly(ADP-ribose) polymerase consists of a polypeptide chain with a molecular weight of 130 000. Ultracentrifugation at non-denaturating conditions indicated that the active enzyme may be an oligomeric form of this polypeptide chain. The isoelectric point of the polymerase was 9.40. The effects of various additions to the assay mixture on the synthesis of poly(ADP-ribose) as well as some kinetic data, are given. It is shown that poly(ADP-ribose) is a highly efficient inhibitor of its own synthesis, and results are presented which suggest that the well-known stimulatory effect of DNA on the synthesis is due to reduction of this inhibitory effect of the product.", "contents": "Poly(ADP-ribose) polymerase from Ehrlich ascites tumor cells. Properties of the purified polymerase. Poly(ADP-ribose) polymerase from Ehrlich ascites tumor cells, partially purified by chromatography on DNA-agarose, was obtained as a more than 80% homogeneous preparation by isoelectric focusing in a sucrose gradient. The polymerase activity was shown to be associated with the major protein in the preparation. Results obtained by electrophoresis in the presence of sodium dodecyl-sulfate indicated that poly(ADP-ribose) polymerase consists of a polypeptide chain with a molecular weight of 130 000. Ultracentrifugation at non-denaturating conditions indicated that the active enzyme may be an oligomeric form of this polypeptide chain. The isoelectric point of the polymerase was 9.40. The effects of various additions to the assay mixture on the synthesis of poly(ADP-ribose) as well as some kinetic data, are given. It is shown that poly(ADP-ribose) is a highly efficient inhibitor of its own synthesis, and results are presented which suggest that the well-known stimulatory effect of DNA on the synthesis is due to reduction of this inhibitory effect of the product."}
{"id": "PMID:211030", "title": "The spin-state transition of the hemochrome non-equilibrium conformation in partially reduced human methemoglobin. A pulse-radiolysis study of aqueous-methanol solutions of methemoglobin.", "content": "The effect of external parameters on the relaxation process of the hemochrome-type non-equilibrium conformation in partially reduced methemoglobin has been investigated. The relaxation of the intermediate ferrous low-spin state to the high-spin equilibrium conformation of hemoglobin appears to be facilitated particularly by protons and phosphate ions. In addition to studying the spin-state transition in aquomethemoglobin we have also studied it in complexes of the heme group in methemoglobin with fluoride, azide and cyanide anions.", "contents": "The spin-state transition of the hemochrome non-equilibrium conformation in partially reduced human methemoglobin. A pulse-radiolysis study of aqueous-methanol solutions of methemoglobin. The effect of external parameters on the relaxation process of the hemochrome-type non-equilibrium conformation in partially reduced methemoglobin has been investigated. The relaxation of the intermediate ferrous low-spin state to the high-spin equilibrium conformation of hemoglobin appears to be facilitated particularly by protons and phosphate ions. In addition to studying the spin-state transition in aquomethemoglobin we have also studied it in complexes of the heme group in methemoglobin with fluoride, azide and cyanide anions."}
{"id": "PMID:211035", "title": "Metabolism of apolipoproteins A-I and A-II and its influence on the high density lipoprotein subfraction distribution in males and females.", "content": "Rate zonal ultracentrifugation of plasma samples from ten healthy age-matched volunteers (five males, five females) indicated that the high density lipoprotein subfraction ratio (HDL2:HDL3) in females was significantly higher than in males. The cause of this phenomenon was investigated by simultaneous examination of the metabolism of the major HDL apoproteins (apoA-I and apoA-II) in both groups. The results show that there is no significant sex-related difference in the plasma pool size, fractional catabolic rate, or synthetic rate of either apoprotein. We conclude that the increased HDL2:HDL3 ratio in femalse versus males does not derive from measurable differences in the metabolic handling of either apoprotein.", "contents": "Metabolism of apolipoproteins A-I and A-II and its influence on the high density lipoprotein subfraction distribution in males and females. Rate zonal ultracentrifugation of plasma samples from ten healthy age-matched volunteers (five males, five females) indicated that the high density lipoprotein subfraction ratio (HDL2:HDL3) in females was significantly higher than in males. The cause of this phenomenon was investigated by simultaneous examination of the metabolism of the major HDL apoproteins (apoA-I and apoA-II) in both groups. The results show that there is no significant sex-related difference in the plasma pool size, fractional catabolic rate, or synthetic rate of either apoprotein. We conclude that the increased HDL2:HDL3 ratio in femalse versus males does not derive from measurable differences in the metabolic handling of either apoprotein."}
{"id": "PMID:211036", "title": "Variations in apolipoproteins B and A1 during the course of myocardial infarction.", "content": "The plasma apolipoproteins B and A1, and plasma lipids and lipoproteins, were studied in fifteen patients with acute myocardial infarction. In the days immediately after acute infarction there was a decrease in total cholesterol, low density lipoprotein-cholesterol, total apolipoprotein-B, low density lipoprotein apolipoprotein-B and high density lipoprotein apolipoprotein A1. High density lipoprotein-cholesterol remained unchanged. In the same period the total triglycerides, very low density lipoprotein-protein, very low density lipoprotein-cholesterol, very low density lipoprotein apolipoprotein-B and very low density lipoprotein apolipoprotein A1 were increased. A reduction of the apolipoprotein ratio CII/CIII occurred after the acute phase. After 25--30 days all these values regained their baseline values.", "contents": "Variations in apolipoproteins B and A1 during the course of myocardial infarction. The plasma apolipoproteins B and A1, and plasma lipids and lipoproteins, were studied in fifteen patients with acute myocardial infarction. In the days immediately after acute infarction there was a decrease in total cholesterol, low density lipoprotein-cholesterol, total apolipoprotein-B, low density lipoprotein apolipoprotein-B and high density lipoprotein apolipoprotein A1. High density lipoprotein-cholesterol remained unchanged. In the same period the total triglycerides, very low density lipoprotein-protein, very low density lipoprotein-cholesterol, very low density lipoprotein apolipoprotein-B and very low density lipoprotein apolipoprotein A1 were increased. A reduction of the apolipoprotein ratio CII/CIII occurred after the acute phase. After 25--30 days all these values regained their baseline values."}
{"id": "PMID:211037", "title": "High density lipoprotein infusion and partial plasma exchange in Tangier disease.", "content": "High density lipoprotein (HDL) infusion and partial plasma exchange were undertaken in two patients homozygous for Tangier disease. Serum samples and ultracentrifugally isolated serum fractions were analysed over a period of 7 days post infusion by agarose electrophoresis, two-dimensional immunoelectrophoresis (employing antibodies to HDL, HDL3, Apoprotein A-I, and Apoprotein A-II), Apoprotein A radioimmunoassay, and analytical polyacrylamide electrophoresis. The following observations were made: (a) immediately after HDL substitution the broad-beta band, normally visible upon agarose electrophoresis of Tangier plasma, resolved into a distinct beta and pre-beta band; (b)as HDL was catabolized, an abnormal alpha-migrating lipoprotein was generated which contained Apoprotein A-II as protein constituent; and (c) there was a proferential loss of Apoprotein A-I from HDL and the plasma compartment in the course of HDL catabolism. The results suggest that the defect in Tangier disease resides with enhanced catabolism or defective synthesis of Apoprotein A-I.", "contents": "High density lipoprotein infusion and partial plasma exchange in Tangier disease. High density lipoprotein (HDL) infusion and partial plasma exchange were undertaken in two patients homozygous for Tangier disease. Serum samples and ultracentrifugally isolated serum fractions were analysed over a period of 7 days post infusion by agarose electrophoresis, two-dimensional immunoelectrophoresis (employing antibodies to HDL, HDL3, Apoprotein A-I, and Apoprotein A-II), Apoprotein A radioimmunoassay, and analytical polyacrylamide electrophoresis. The following observations were made: (a) immediately after HDL substitution the broad-beta band, normally visible upon agarose electrophoresis of Tangier plasma, resolved into a distinct beta and pre-beta band; (b)as HDL was catabolized, an abnormal alpha-migrating lipoprotein was generated which contained Apoprotein A-II as protein constituent; and (c) there was a proferential loss of Apoprotein A-I from HDL and the plasma compartment in the course of HDL catabolism. The results suggest that the defect in Tangier disease resides with enhanced catabolism or defective synthesis of Apoprotein A-I."}
{"id": "PMID:211038", "title": "Serum lipoprotiens in four European communities: a quantitative comparison.", "content": "Serum lipid and lipoprotein concentrations have been measured in 985 men and women sampled from communities in London, Naples, Uppsala and Geneva. This was done to define normal ranges, detect inter-population differences, and relate such differences to levels of lipids in the major lipoprotein classes of plasma. Cholesterol and triglyceride concentrations showed substantial differences between the four populations; levels of these lipids showed parallel trends, which were attributable to differences in low density lipoprotein and very low density lipoprotein concentrations. By contrast, high density lipoprotein cholesterol concentrations showed little or no interpopulation differences. Geographical differences in serum triglyceride and cholesterol levels were not correlated with variation in the prevalence of obesity.", "contents": "Serum lipoprotiens in four European communities: a quantitative comparison. Serum lipid and lipoprotein concentrations have been measured in 985 men and women sampled from communities in London, Naples, Uppsala and Geneva. This was done to define normal ranges, detect inter-population differences, and relate such differences to levels of lipids in the major lipoprotein classes of plasma. Cholesterol and triglyceride concentrations showed substantial differences between the four populations; levels of these lipids showed parallel trends, which were attributable to differences in low density lipoprotein and very low density lipoprotein concentrations. By contrast, high density lipoprotein cholesterol concentrations showed little or no interpopulation differences. Geographical differences in serum triglyceride and cholesterol levels were not correlated with variation in the prevalence of obesity."}
{"id": "PMID:211039", "title": "The effects of alpha and beta adrenergic agents on spleen cell antigen binding in four amphibian species.", "content": "Adults of two urodele amphibian species (Triturus cristatus carnifex and Cynops hongkongensis) and two anuran species (Rana temporaria and Xenopus laevis laevis) were immunized with a 25% suspension of sheep or horse erythrocytes. After eight or 14 days, splenic lymphocytes were removed, and their specific red cell-binding capacities tested by immunocytoadherence. Antigen-binding cells were classified as high-dose nonsecretory (S-) or secretory (S+), according to whether they bound a single layer or several layers or erythrocytes. The stimulation of both alpha and beta adrenoreceptors reduced the numbers of S+ rosettes formed by Triturus and Cynops lymphocytes, whereas a beta agonist increased and an alpha agonist decreased S+ rosette formation by Rana and Xenopus splenic lymphocytes. These effects were blocked by alpha and beta adrenoreceptor antagonists. Low-dose immunization of Xenopus with a 0.0025% suspension of sheep erythrocytes gave a minimal number of S+ rosettes two and eight days after immunization, and beta adrenoreceptor stimulation had no effect on antigen binding. These results are discussed in terms of the distribution of alpha and beta adrenoreceptors in amphibians and possible relationships between S+ and high-dose S- antigen-binding cells, and support the view that functional lymphocyte heterogeneity exists in these lower vertebrates.", "contents": "The effects of alpha and beta adrenergic agents on spleen cell antigen binding in four amphibian species. Adults of two urodele amphibian species (Triturus cristatus carnifex and Cynops hongkongensis) and two anuran species (Rana temporaria and Xenopus laevis laevis) were immunized with a 25% suspension of sheep or horse erythrocytes. After eight or 14 days, splenic lymphocytes were removed, and their specific red cell-binding capacities tested by immunocytoadherence. Antigen-binding cells were classified as high-dose nonsecretory (S-) or secretory (S+), according to whether they bound a single layer or several layers or erythrocytes. The stimulation of both alpha and beta adrenoreceptors reduced the numbers of S+ rosettes formed by Triturus and Cynops lymphocytes, whereas a beta agonist increased and an alpha agonist decreased S+ rosette formation by Rana and Xenopus splenic lymphocytes. These effects were blocked by alpha and beta adrenoreceptor antagonists. Low-dose immunization of Xenopus with a 0.0025% suspension of sheep erythrocytes gave a minimal number of S+ rosettes two and eight days after immunization, and beta adrenoreceptor stimulation had no effect on antigen binding. These results are discussed in terms of the distribution of alpha and beta adrenoreceptors in amphibians and possible relationships between S+ and high-dose S- antigen-binding cells, and support the view that functional lymphocyte heterogeneity exists in these lower vertebrates."}
{"id": "PMID:211040", "title": "Activation of the alternative complement pathway by human B cell lymphoma lines is associated with Epstein-Barr virus transformation of the cells.", "content": "Activation of the alternative complement pathway by human B cell lymphoma lines is correlated with the presence of Epstein Barr virus (EBV) in the cell genome. EBV-negative B cell lymphoma lines produce little activation of the alternative pathway as measured either by C3 deposition on the cell surface or C3 conversion and consumption of alternative pathway activity in the supernatant serum. By contrast, EBV-positive sublines derived by in vitro EBV conversion of EBV-negative parental lines produce considerable activation of the alternative pathway. This membrane-associated complement-activating mechanism reflects an EBV-induced membrane change in these cells and may provide a mechanism whereby EBV-transformed cells are controlled in vivo.", "contents": "Activation of the alternative complement pathway by human B cell lymphoma lines is associated with Epstein-Barr virus transformation of the cells. Activation of the alternative complement pathway by human B cell lymphoma lines is correlated with the presence of Epstein Barr virus (EBV) in the cell genome. EBV-negative B cell lymphoma lines produce little activation of the alternative pathway as measured either by C3 deposition on the cell surface or C3 conversion and consumption of alternative pathway activity in the supernatant serum. By contrast, EBV-positive sublines derived by in vitro EBV conversion of EBV-negative parental lines produce considerable activation of the alternative pathway. This membrane-associated complement-activating mechanism reflects an EBV-induced membrane change in these cells and may provide a mechanism whereby EBV-transformed cells are controlled in vivo."}
{"id": "PMID:211041", "title": "Caffeine elicited withdrawal signs in morphine-dependent rhesus monkeys.", "content": "In the dose range of 4.0--32.0 mg/kg s.c., caffeine produced most of the signs which are commonly seen after the administration of naloxone (0.05 mg/kg s.c.) to morphine-dependent monkeys. The signs designated as lying on side or abdomen, avoiding contact, vocalizing, crawling or rolling, restlessness or pacing, tremors, retching, vomiting, coughing, vocalizing when abdomen palpated, rigid abdomen and salivation were noted. A randomized and blind experimental design, which included vehicle and positive (naloxone) controls was used. The significance of the differences between total scores for the whole syndrome was tested by the Mann-Whitney U-test. In preliminary studies in naive monkeys, caffeine was found to elicit some withdrawal signs but the results were equivocal. Na benzoate also elicited some withdrawal signs in morphine-dependent monkeys at 32.0 mg/kg s.c., but few signs were seen in naive monkeys. Caffeine was found to be approximately 10X more active than Na benzoate in inhibiting cAMP phosphodiesterase activity in a neuroblastoma cell whole homogenate assay. These results are consistent with the observations of Collier and Francis that morphine abstinence in rodents is associated with increased brain levels of cAMP.", "contents": "Caffeine elicited withdrawal signs in morphine-dependent rhesus monkeys. In the dose range of 4.0--32.0 mg/kg s.c., caffeine produced most of the signs which are commonly seen after the administration of naloxone (0.05 mg/kg s.c.) to morphine-dependent monkeys. The signs designated as lying on side or abdomen, avoiding contact, vocalizing, crawling or rolling, restlessness or pacing, tremors, retching, vomiting, coughing, vocalizing when abdomen palpated, rigid abdomen and salivation were noted. A randomized and blind experimental design, which included vehicle and positive (naloxone) controls was used. The significance of the differences between total scores for the whole syndrome was tested by the Mann-Whitney U-test. In preliminary studies in naive monkeys, caffeine was found to elicit some withdrawal signs but the results were equivocal. Na benzoate also elicited some withdrawal signs in morphine-dependent monkeys at 32.0 mg/kg s.c., but few signs were seen in naive monkeys. Caffeine was found to be approximately 10X more active than Na benzoate in inhibiting cAMP phosphodiesterase activity in a neuroblastoma cell whole homogenate assay. These results are consistent with the observations of Collier and Francis that morphine abstinence in rodents is associated with increased brain levels of cAMP."}
{"id": "PMID:211042", "title": "Distinct dopaminergic systems in ACTH-induced grooming.", "content": "Excessive grooming behavior induced in rats by intraventricular injection of ACTH1-24 was inhibited by selective pharmacological manipulation of two functionally distinct types of dopaminergic terminals (DAe and DAi) in the neostriatum or the nucleus accumbens. It is concluded that when ACTH1-24 produces the behavioral response it modulates the activity of both the DAe and the DAi systems.", "contents": "Distinct dopaminergic systems in ACTH-induced grooming. Excessive grooming behavior induced in rats by intraventricular injection of ACTH1-24 was inhibited by selective pharmacological manipulation of two functionally distinct types of dopaminergic terminals (DAe and DAi) in the neostriatum or the nucleus accumbens. It is concluded that when ACTH1-24 produces the behavioral response it modulates the activity of both the DAe and the DAi systems."}
{"id": "PMID:211044", "title": "The role of protein synthesis in polymorphonuclear leukocyte phagocytosis II.", "content": "Polymorphonuclear leukocytes collected from healthy human volunteers were treated with puromycin which inhibited protein synthesis in the cell. The neutrophils exhibited a marked decrease in phagocytosis after 1 h. The myeloperoxidase mediated conversion of iodide to a protein-bound form was also decreased. Hexosemonophosphate shunt activity remained similar for both puromycin treated PMN and control cells at 1 h. The results suggest that new protein synthesis is necessary to maintain PMN function at full capacity.", "contents": "The role of protein synthesis in polymorphonuclear leukocyte phagocytosis II. Polymorphonuclear leukocytes collected from healthy human volunteers were treated with puromycin which inhibited protein synthesis in the cell. The neutrophils exhibited a marked decrease in phagocytosis after 1 h. The myeloperoxidase mediated conversion of iodide to a protein-bound form was also decreased. Hexosemonophosphate shunt activity remained similar for both puromycin treated PMN and control cells at 1 h. The results suggest that new protein synthesis is necessary to maintain PMN function at full capacity."}
{"id": "PMID:211045", "title": "Mobilization of CFU-C by exercise and ACTH induced stress in man.", "content": "This study was designed to investigate physiological factors that affect blood CFU-C numbers. Exercise was found to produce a fourfold rise in blood colony forming cells, and a twofold rise in cluster forming cells accompanied by a lymphocytosis. ACTH-induced stress caused a twofold rise in blood colony and cluster forming cells accompanied by a neutrophil leucocytosis. The results suggest that blood CFU-C exchange with a large marginal pool as well as a bone marrown pool. The procedures described could be exploited in the use of leukapheresed nucleated cells as a source of stem cells for bone marrow transplantation.", "contents": "Mobilization of CFU-C by exercise and ACTH induced stress in man. This study was designed to investigate physiological factors that affect blood CFU-C numbers. Exercise was found to produce a fourfold rise in blood colony forming cells, and a twofold rise in cluster forming cells accompanied by a lymphocytosis. ACTH-induced stress caused a twofold rise in blood colony and cluster forming cells accompanied by a neutrophil leucocytosis. The results suggest that blood CFU-C exchange with a large marginal pool as well as a bone marrown pool. The procedures described could be exploited in the use of leukapheresed nucleated cells as a source of stem cells for bone marrow transplantation."}
{"id": "PMID:211046", "title": "The effect of peripheral nerve cross-union on connections of single Ia fibers to motoneurons.", "content": "The distribution of Ia terminals to alpha-motoneurons has been investigated under conditions where a) the Ia fiber innervates a foreign muscle and b) the motor axon innervates a foreign muscle. This distribution has been assessed by examining which motoneurons develop an EPSP in response to stimulation of a single Ia afferent fiber. Cross-union of the medial gastrocnemius and lateral gastrocnemius-soleus nerves has been performed in 5--8 day old kittens and the effect of this procedure on Ia connections to alpha-motoneurons has been investigated in the adult about one year later. No rearrangement of synaptic connections has been observed under these conditions. The connections from self-unioned Ia afferents and to self-unioned motoneurons are also normal. The individual EPSP's in these motoneurons with regenerated axons have normal rise times. The findings of normal Ia connections as well as normal EPSP rise times in alpha-motoneurons with regenerated motor axons indicates reversibility of the changes seen in axotomized motoneurons.", "contents": "The effect of peripheral nerve cross-union on connections of single Ia fibers to motoneurons. The distribution of Ia terminals to alpha-motoneurons has been investigated under conditions where a) the Ia fiber innervates a foreign muscle and b) the motor axon innervates a foreign muscle. This distribution has been assessed by examining which motoneurons develop an EPSP in response to stimulation of a single Ia afferent fiber. Cross-union of the medial gastrocnemius and lateral gastrocnemius-soleus nerves has been performed in 5--8 day old kittens and the effect of this procedure on Ia connections to alpha-motoneurons has been investigated in the adult about one year later. No rearrangement of synaptic connections has been observed under these conditions. The connections from self-unioned Ia afferents and to self-unioned motoneurons are also normal. The individual EPSP's in these motoneurons with regenerated axons have normal rise times. The findings of normal Ia connections as well as normal EPSP rise times in alpha-motoneurons with regenerated motor axons indicates reversibility of the changes seen in axotomized motoneurons."}
{"id": "PMID:211047", "title": "Study of antiblastomogenic action of epidermal chalones. I. The effect of epidermal chalones on some transplantable mouse tumours.", "content": "The effect of chalone-containing ethanol extract of rat skin (CCE) on the growth in mice of transplanted uterine cervix and skin carcinomas, hepatoma-22a, sarcoma-180 and leukemia L-1210 was studied. When CCE is added to the suspension of tumour cells (10 mg CCE/100 mg tumour tissue/ml saline) the most obvious retention of tumour growth is observed on squamous-cell carcinoma of uterine cervix (72.6%; p less than 0.01). The effect of CCE on the growth of other transplanted tumours, including the skin carcinoma, is not significant. As compared to the uterine cervix carcinoma, the skin carcinoma lacked its primary squamous-cell structure during the tumour progression. The possibility of applicative use of chalones for cancer control is discussed.", "contents": "Study of antiblastomogenic action of epidermal chalones. I. The effect of epidermal chalones on some transplantable mouse tumours. The effect of chalone-containing ethanol extract of rat skin (CCE) on the growth in mice of transplanted uterine cervix and skin carcinomas, hepatoma-22a, sarcoma-180 and leukemia L-1210 was studied. When CCE is added to the suspension of tumour cells (10 mg CCE/100 mg tumour tissue/ml saline) the most obvious retention of tumour growth is observed on squamous-cell carcinoma of uterine cervix (72.6%; p less than 0.01). The effect of CCE on the growth of other transplanted tumours, including the skin carcinoma, is not significant. As compared to the uterine cervix carcinoma, the skin carcinoma lacked its primary squamous-cell structure during the tumour progression. The possibility of applicative use of chalones for cancer control is discussed."}
{"id": "PMID:211050", "title": "Initiation of sperm motility in the mammalian epididymis.", "content": "Spermatozoa acquire the capacity for motility as they traverse the mammalian epididymis. The biochemical basis for this induction of motility is still largely unknown. Current theories are discussed and recent studies from the authors' laboratory are described which indicate that two separate processes are involved and that these act synergistically. These processes are an increase in the intrasperm content of cyclic AMP during epididymal transit combined with the binding of a specific forward-motility protein. A second increase in cyclic AMP and stimulation by calcium ion is likely involved in the expression of the acquired potential for motility at the time of ejaculation.", "contents": "Initiation of sperm motility in the mammalian epididymis. Spermatozoa acquire the capacity for motility as they traverse the mammalian epididymis. The biochemical basis for this induction of motility is still largely unknown. Current theories are discussed and recent studies from the authors' laboratory are described which indicate that two separate processes are involved and that these act synergistically. These processes are an increase in the intrasperm content of cyclic AMP during epididymal transit combined with the binding of a specific forward-motility protein. A second increase in cyclic AMP and stimulation by calcium ion is likely involved in the expression of the acquired potential for motility at the time of ejaculation."}
{"id": "PMID:211051", "title": "[Role of the paradoxical stage in the organization of the sleep--wakefulness cycle in rats].", "content": "In chronic experiments on rats, using the Jouvet technique, paradoxical sleep deprivation entailed disturbances in both the sleep cycle and the mechanism for regulation of the circadian sleep--wakefulness cycle. The sleep cycle disturbances involved, in the first place, a considerable reduction of the paradoxical sleep, diminishing of the profound slow-wave sleep, and an increase in duration of the light slow-wave sleep. These shifts were clear on the 1st day of the deprivation and considerably reduced on the 2nd day due to an increasing rate of alternation of the sleep--wakefulness cycle's phases. The data obtained suggest a certain commonness of the mechanisms for control of the slow-wave and the paradoxical phases of sleep, as well as the great compensatory abilities of the organism at the paradoxical sleep deprivation.", "contents": "[Role of the paradoxical stage in the organization of the sleep--wakefulness cycle in rats]. In chronic experiments on rats, using the Jouvet technique, paradoxical sleep deprivation entailed disturbances in both the sleep cycle and the mechanism for regulation of the circadian sleep--wakefulness cycle. The sleep cycle disturbances involved, in the first place, a considerable reduction of the paradoxical sleep, diminishing of the profound slow-wave sleep, and an increase in duration of the light slow-wave sleep. These shifts were clear on the 1st day of the deprivation and considerably reduced on the 2nd day due to an increasing rate of alternation of the sleep--wakefulness cycle's phases. The data obtained suggest a certain commonness of the mechanisms for control of the slow-wave and the paradoxical phases of sleep, as well as the great compensatory abilities of the organism at the paradoxical sleep deprivation."}
{"id": "PMID:211052", "title": "[Deprivation of \"rapid\" sleep by stimulation of the reticular formation of rats].", "content": "Rats were repeatedly arused from REM sleep by the stimulation via implanted midbrain reticular electrodes. The 4-day seprivation reduced REM sleep by 50% whereas the slow-wave sleep was only reduced by 10%. There was no evidence of a disruption in the animal behaviour during the deprivation and no changes of emotional responsiveness in the \"open-field\" at the end of the deprivation. REM deprivation produced a slight but statistically significant (P = 0.025) adrenal weightlos. Thymus weight was unchanged and no stomach ulcers developed. Therefore the REM deprivation as such did not appear to produce stress in rats.", "contents": "[Deprivation of \"rapid\" sleep by stimulation of the reticular formation of rats]. Rats were repeatedly arused from REM sleep by the stimulation via implanted midbrain reticular electrodes. The 4-day seprivation reduced REM sleep by 50% whereas the slow-wave sleep was only reduced by 10%. There was no evidence of a disruption in the animal behaviour during the deprivation and no changes of emotional responsiveness in the \"open-field\" at the end of the deprivation. REM deprivation produced a slight but statistically significant (P = 0.025) adrenal weightlos. Thymus weight was unchanged and no stomach ulcers developed. Therefore the REM deprivation as such did not appear to produce stress in rats."}
{"id": "PMID:211053", "title": "[Metabolic structure of the restitution process following physical loads of a different character].", "content": "The result of biochemical and mathematical analysis of restitution processes after various exercises determined the phases of these processes and the interrelationship between metabolic structure of restitution and the character of exercise. Metabolic structure of restitution has some common traits in recovery period after non-fatiguing exercises and exercises causing a rapidly developing fatigue. In contrast, sharp changes of this structure occur after exercises causing a slowly developing exhaustion.", "contents": "[Metabolic structure of the restitution process following physical loads of a different character]. The result of biochemical and mathematical analysis of restitution processes after various exercises determined the phases of these processes and the interrelationship between metabolic structure of restitution and the character of exercise. Metabolic structure of restitution has some common traits in recovery period after non-fatiguing exercises and exercises causing a rapidly developing fatigue. In contrast, sharp changes of this structure occur after exercises causing a slowly developing exhaustion."}
{"id": "PMID:211055", "title": "[Effects of several estrogenic compounds on serum corticosteroid-binding globulin (CBG) and the estrogen thresholds for increasing CBG (author's transl)].", "content": "The effects of several estrogen substances--alone, or in combination with norgestrel--on serum CBG in humans are reported in this paper. CBG was measured by a modified charcoal adsorption technique. Daily oral doses of Premarin, from 0.3 to 2.5mg, were given to healthy postmenopausal women for 14 days. Dose-dependent increases in CBG-BC were observed. Ovral, which contains ethinylestradiol and norgestrel, also induced significant increases in the levels of CBG-BC. Similar results were seen with Lo Ovral, but it had less influence than Ovral. When given alone, daily for 21 days, norgestrel had no effect on CBG-BC. The maximum rise of serum CBG-BC was found after 10 days of the daily doses of Ovral, and then the levels remained quite constant during the period of treatment. Exogenous estrogens of other types also caused increases in CBG-BC. The response of CBG to exogenous estrogens is of use in comparing the estrogen potencies of the compounds. CBG-BC levels remained constant throughout the menstrual cycle in five normal women despite fluctuating levels of estradiol which reached peaks of 190 approximately 430 pg/ml. In pregnant women and in HMG-treated women, however, serum levels of CBG-BC increased beginning when estradiol levels were greater than 1 ng/ml.", "contents": "[Effects of several estrogenic compounds on serum corticosteroid-binding globulin (CBG) and the estrogen thresholds for increasing CBG (author's transl)]. The effects of several estrogen substances--alone, or in combination with norgestrel--on serum CBG in humans are reported in this paper. CBG was measured by a modified charcoal adsorption technique. Daily oral doses of Premarin, from 0.3 to 2.5mg, were given to healthy postmenopausal women for 14 days. Dose-dependent increases in CBG-BC were observed. Ovral, which contains ethinylestradiol and norgestrel, also induced significant increases in the levels of CBG-BC. Similar results were seen with Lo Ovral, but it had less influence than Ovral. When given alone, daily for 21 days, norgestrel had no effect on CBG-BC. The maximum rise of serum CBG-BC was found after 10 days of the daily doses of Ovral, and then the levels remained quite constant during the period of treatment. Exogenous estrogens of other types also caused increases in CBG-BC. The response of CBG to exogenous estrogens is of use in comparing the estrogen potencies of the compounds. CBG-BC levels remained constant throughout the menstrual cycle in five normal women despite fluctuating levels of estradiol which reached peaks of 190 approximately 430 pg/ml. In pregnant women and in HMG-treated women, however, serum levels of CBG-BC increased beginning when estradiol levels were greater than 1 ng/ml."}
{"id": "PMID:211056", "title": "So-called multicentric pigmented Bowen's disease. Report of a case and a possible etiologic role of human papilloma virus.", "content": "Multicentric pigmented Bowen's disease (MPBD) is a bowenoid atypia in the genitocrural region with peculiar clinical appearances. A 36-year-old Japanese female patient showed a variety of lesions. Clinically the lesions on the external genitalia consisted of brown-black papillomatous eruptions, black discrete or confluent papules, and whitish macerated papules. Histologically only black papules showed bowenoid atypia, but whitish papules also showed transient bowenoid atypia. Electron microscopically, in all three kinds of the lesions, spherical particles with a diameter of about 50 nm were scattered or gathered together in the nuclei of the keratinocytes beneath the horny layer. These particles were morphologically similar to human papilloma virus. Based upon clinical, histologic and electron microscopic observations, MPBD may be regarded as a new entity, and a term such as multicentric pigmented viral papulosis may be rather preferable than MPBD.", "contents": "So-called multicentric pigmented Bowen's disease. Report of a case and a possible etiologic role of human papilloma virus. Multicentric pigmented Bowen's disease (MPBD) is a bowenoid atypia in the genitocrural region with peculiar clinical appearances. A 36-year-old Japanese female patient showed a variety of lesions. Clinically the lesions on the external genitalia consisted of brown-black papillomatous eruptions, black discrete or confluent papules, and whitish macerated papules. Histologically only black papules showed bowenoid atypia, but whitish papules also showed transient bowenoid atypia. Electron microscopically, in all three kinds of the lesions, spherical particles with a diameter of about 50 nm were scattered or gathered together in the nuclei of the keratinocytes beneath the horny layer. These particles were morphologically similar to human papilloma virus. Based upon clinical, histologic and electron microscopic observations, MPBD may be regarded as a new entity, and a term such as multicentric pigmented viral papulosis may be rather preferable than MPBD."}
{"id": "PMID:211057", "title": "Distribution of adenylate cyclase among membrane fractions of rat liver.", "content": "Adenylate cyclase activity was detected in plasma membranes, Golgi apparatus, and endoplasmic reticulum from rat liver. Adenylate cyclase activities of purified membranes were determined biochemically by two methods. In one, the synthesis of radioactive cyclic AMP from ATalpha32P was monitored. In the other, the synthesis of cyclic AMP was quantitiated using a protein which specifically binds cyclic AMP. The enzyme activity was responsive to activation by both glucagon and sodium fluoride although differences in degree of activation were noted comparing plasma membrane, Golgi apparatus, and endoplasmic reticulum. Cytochemical studies, using both whole tissue and purified cell fractions and conducted in parallel, confirmed the biochemical results. Deposition of lead phosphate, enhanced by glucagon and NaF with samples incubated with appropriate substrates, was not restricted to plasma membranes of hepatocytes but was present in intracellular membranes as well. Adenylate cyclase of rat hepatocytes appears more widely distributed among internal membranes than previously recognized.", "contents": "Distribution of adenylate cyclase among membrane fractions of rat liver. Adenylate cyclase activity was detected in plasma membranes, Golgi apparatus, and endoplasmic reticulum from rat liver. Adenylate cyclase activities of purified membranes were determined biochemically by two methods. In one, the synthesis of radioactive cyclic AMP from ATalpha32P was monitored. In the other, the synthesis of cyclic AMP was quantitiated using a protein which specifically binds cyclic AMP. The enzyme activity was responsive to activation by both glucagon and sodium fluoride although differences in degree of activation were noted comparing plasma membrane, Golgi apparatus, and endoplasmic reticulum. Cytochemical studies, using both whole tissue and purified cell fractions and conducted in parallel, confirmed the biochemical results. Deposition of lead phosphate, enhanced by glucagon and NaF with samples incubated with appropriate substrates, was not restricted to plasma membranes of hepatocytes but was present in intracellular membranes as well. Adenylate cyclase of rat hepatocytes appears more widely distributed among internal membranes than previously recognized."}
{"id": "PMID:211058", "title": "Transformation of skin fibroblast cells of a cystinotic patient by simian virus 40: evidence for an establishment of a permanent cell clone which retains the original metabolism defect.", "content": "Human skin fibroblast cells derived from a juvenile patient with nephropathic cystinosis were transformed by simian virus 40. Transformed cell clones were isolated and established in tissue culture. In comparison to the parental cystinotic cells, the newly isolated, transformed cell clones had a higher plating efficiency, a modal chromosome number of 68, grew in soft agar, and showed a nuclear immunofluorescence typical for SV 40-specific tumor (T) antigen. The content of intracellular, unbound cystine in the transformed cell clone was of the same level (6.1 nmol 1/2 cystine/mg protein) as in the parental cystinotic cells (7.4 nmol). Control cells (SV 80 and WI-38) contained normal levels of cystine (0.31 and 0.47 nmol 1/2 cystine/mg protein). The growth characteristics make the transformed cystinotic cell clone suitable for large scale preparation of cellular constituents, i.e. lysosomes which seem to be affected in cystinotic patients.", "contents": "Transformation of skin fibroblast cells of a cystinotic patient by simian virus 40: evidence for an establishment of a permanent cell clone which retains the original metabolism defect. Human skin fibroblast cells derived from a juvenile patient with nephropathic cystinosis were transformed by simian virus 40. Transformed cell clones were isolated and established in tissue culture. In comparison to the parental cystinotic cells, the newly isolated, transformed cell clones had a higher plating efficiency, a modal chromosome number of 68, grew in soft agar, and showed a nuclear immunofluorescence typical for SV 40-specific tumor (T) antigen. The content of intracellular, unbound cystine in the transformed cell clone was of the same level (6.1 nmol 1/2 cystine/mg protein) as in the parental cystinotic cells (7.4 nmol). Control cells (SV 80 and WI-38) contained normal levels of cystine (0.31 and 0.47 nmol 1/2 cystine/mg protein). The growth characteristics make the transformed cystinotic cell clone suitable for large scale preparation of cellular constituents, i.e. lysosomes which seem to be affected in cystinotic patients."}
{"id": "PMID:211061", "title": "Polygraphic studies of kitten development: respiratory rate and variability during sleep-waking states.", "content": "The developmental course of respiration rate and variability during sleep states and waking was measured in chronically prepared kittens. Kittens had higher respiration rates during active sleep (AS) as compared to quiet sleep (QS) at all ages, with rates declining developmentally in both sleep states. Compared to waking, respiration rate and variability were decreased during sleep. The decrease was greatest in the youngest animals and during QS. Minute-to-minute respiratory variability declined from 10 to 40 days of age for each state, whereas breath-to-breath variability declined during the same period only during QS. Respiratory variability was higher in AS than QS in older kittens. Heart rate and variability were found to be correlated with respiratory parameters only during QS. These observations support the hypothesis that the control and development of respiration during sleep is achieved by different processes in QS and AS.", "contents": "Polygraphic studies of kitten development: respiratory rate and variability during sleep-waking states. The developmental course of respiration rate and variability during sleep states and waking was measured in chronically prepared kittens. Kittens had higher respiration rates during active sleep (AS) as compared to quiet sleep (QS) at all ages, with rates declining developmentally in both sleep states. Compared to waking, respiration rate and variability were decreased during sleep. The decrease was greatest in the youngest animals and during QS. Minute-to-minute respiratory variability declined from 10 to 40 days of age for each state, whereas breath-to-breath variability declined during the same period only during QS. Respiratory variability was higher in AS than QS in older kittens. Heart rate and variability were found to be correlated with respiratory parameters only during QS. These observations support the hypothesis that the control and development of respiration during sleep is achieved by different processes in QS and AS."}
{"id": "PMID:211064", "title": "Effect of N-(3,5-dichlorophenyl)succinimide on the histological pattern and incidence of kidney tumors induced by streptozotocin rats.", "content": "The effect of the nephrotoxic substance, N-(3,5-dichlorophenyl)succinimide, on the histological pattern and incidence of kidney tumors induced by streptozotocin in rats was studied. In groups administered streptozotocin alone or in combination with nicotinamide, the histological pattern and the incidence of kidney tumors in rats were similar; renal cell tumors developed in 1 of 9 rats (11.1%) and in 2 of 17 rats (11.8%), respectively. However, post-treatment with N-(3,5-dichlorophenyl)succinimide increased the induction of epithelial tumors by streptozotocin, and embryonal cell tumors were also induced nearly as frequently. Administration of nicotinamide alone did not result in the development of kidney tumors.", "contents": "Effect of N-(3,5-dichlorophenyl)succinimide on the histological pattern and incidence of kidney tumors induced by streptozotocin rats. The effect of the nephrotoxic substance, N-(3,5-dichlorophenyl)succinimide, on the histological pattern and incidence of kidney tumors induced by streptozotocin in rats was studied. In groups administered streptozotocin alone or in combination with nicotinamide, the histological pattern and the incidence of kidney tumors in rats were similar; renal cell tumors developed in 1 of 9 rats (11.1%) and in 2 of 17 rats (11.8%), respectively. However, post-treatment with N-(3,5-dichlorophenyl)succinimide increased the induction of epithelial tumors by streptozotocin, and embryonal cell tumors were also induced nearly as frequently. Administration of nicotinamide alone did not result in the development of kidney tumors."}
{"id": "PMID:211065", "title": "Application of the transfection technique for segregation of avian tumor viruses.", "content": "The possibility of clong avian tumor virus (ATV) by the transfection technique was studied. The attempts required efficient facilitator for the uptake of exogenous cellular DNA by chick embryo cells (CEC) to increase transfection efficiency. The calcium method was more efficient than the DEAE-dextran method for the uptake of tritium-labeled DNA, and the calcium method was used in further segregation studies of ATV by transfection of cellular DNA from ATV-infected cells. The test viruses included the BAI-A strain of avian myeloblastosis virus (a mixture of subgroup A and B viruses) and the B77 strain of avian sarcoma virus (a mixture of transforming and transformation-defective viruses). Analysis of the recovered progeny viruses after transfection revealed that they were indeed segregates of the parent viruses.", "contents": "Application of the transfection technique for segregation of avian tumor viruses. The possibility of clong avian tumor virus (ATV) by the transfection technique was studied. The attempts required efficient facilitator for the uptake of exogenous cellular DNA by chick embryo cells (CEC) to increase transfection efficiency. The calcium method was more efficient than the DEAE-dextran method for the uptake of tritium-labeled DNA, and the calcium method was used in further segregation studies of ATV by transfection of cellular DNA from ATV-infected cells. The test viruses included the BAI-A strain of avian myeloblastosis virus (a mixture of subgroup A and B viruses) and the B77 strain of avian sarcoma virus (a mixture of transforming and transformation-defective viruses). Analysis of the recovered progeny viruses after transfection revealed that they were indeed segregates of the parent viruses."}
{"id": "PMID:211066", "title": "Inhibition of macrophage-mediated cytolysis by lipoproteins from cell-free tumorous ascites.", "content": "Cell-free ascites from syngeneic MM46 tumor-bearing C3H/He mice inhibited the antibody-dependent macrophage-mediated tumor lysis in vitro and the inhibitiory activity increased with the period of tumor bearing. Thus, the inhibitory activity was demonstrated at the effector cell level. Three fractions of lipoprotein and a protein-rich fraction were prepared from the cell-free ascites by sequential flotation. Among these, the very low density (p less than 1.006) and low density (1.006 less than p less than 1.063) lipoprotein fractions inhibited tumor lysis mediated by activated macrophages and syngeneic antitumor antibody, whereas the high density (1.063 less than p less than 1.21) lipoprotein and the protein-rich infranatant fractions did not. This inhibitory activity at the effector cell level may be due to functional depression of macrophages by lipoprotein fractions.", "contents": "Inhibition of macrophage-mediated cytolysis by lipoproteins from cell-free tumorous ascites. Cell-free ascites from syngeneic MM46 tumor-bearing C3H/He mice inhibited the antibody-dependent macrophage-mediated tumor lysis in vitro and the inhibitiory activity increased with the period of tumor bearing. Thus, the inhibitory activity was demonstrated at the effector cell level. Three fractions of lipoprotein and a protein-rich fraction were prepared from the cell-free ascites by sequential flotation. Among these, the very low density (p less than 1.006) and low density (1.006 less than p less than 1.063) lipoprotein fractions inhibited tumor lysis mediated by activated macrophages and syngeneic antitumor antibody, whereas the high density (1.063 less than p less than 1.21) lipoprotein and the protein-rich infranatant fractions did not. This inhibitory activity at the effector cell level may be due to functional depression of macrophages by lipoprotein fractions."}
{"id": "PMID:211067", "title": "Electron microscopic observation of scirrhous carcinoma of the stomach.", "content": "Electron microscopic findings obtained from seven scirrhous carcinomas of the stomach were analyzed dividing each carcinoma into superficial, deep, and peripheral parts. Proliferation of collagen fibrils, disappearance of plasma membranes, and extracellular release of cell organellae of cancer cells were considered to be peculiar findings to this type of cancer. These phenomena were observed frequently at the deep part of the cancer, but rarely at the peripheral and superficial parts. Replacement of damaged cells by the proliferated collagen fibrils at the central area of the cancer and disconnection of cancer cells from scirrhous lesion at the peripheral part were considered to contribute to the biological behaviour of this carcinoma.", "contents": "Electron microscopic observation of scirrhous carcinoma of the stomach. Electron microscopic findings obtained from seven scirrhous carcinomas of the stomach were analyzed dividing each carcinoma into superficial, deep, and peripheral parts. Proliferation of collagen fibrils, disappearance of plasma membranes, and extracellular release of cell organellae of cancer cells were considered to be peculiar findings to this type of cancer. These phenomena were observed frequently at the deep part of the cancer, but rarely at the peripheral and superficial parts. Replacement of damaged cells by the proliferated collagen fibrils at the central area of the cancer and disconnection of cancer cells from scirrhous lesion at the peripheral part were considered to contribute to the biological behaviour of this carcinoma."}
{"id": "PMID:211068", "title": "Deletions of the iso-1-cytochrome c and adjacent genes of yeast: discovery of the OSM1 gene controlling osmotic sensitivity.", "content": "Some of the deletions in the yeast Saccharomyces cerevisiae that encompass the CYC1 gene, which determines iso-1-cytochrome c, extend into the OSM1 gene, causing inhibition of growth on hypertonic media, and into the RAD7 gene, causing sensitivity to UV light. Two deletions (cyc1--363 and cyc1--367) encompass only the CYC1 gene, two deletions (cyc1--366 and cyc1--368) encompass the CYC1 and OSM1 genes, three deletions (cyc1--1, cyc1--364 and cyc1--365) encompass the CYC1, OSM1 and RAD7 genes, while none of the deletions extend into the closely linked SUP4 gene.", "contents": "Deletions of the iso-1-cytochrome c and adjacent genes of yeast: discovery of the OSM1 gene controlling osmotic sensitivity. Some of the deletions in the yeast Saccharomyces cerevisiae that encompass the CYC1 gene, which determines iso-1-cytochrome c, extend into the OSM1 gene, causing inhibition of growth on hypertonic media, and into the RAD7 gene, causing sensitivity to UV light. Two deletions (cyc1--363 and cyc1--367) encompass only the CYC1 gene, two deletions (cyc1--366 and cyc1--368) encompass the CYC1 and OSM1 genes, three deletions (cyc1--1, cyc1--364 and cyc1--365) encompass the CYC1, OSM1 and RAD7 genes, while none of the deletions extend into the closely linked SUP4 gene."}
{"id": "PMID:211069", "title": "[Analysis of mutation frequency following continuous and fractionated application of ethyleneimine and ethyl methanesulfonate to male sex cells of Drosophila melanogaster].", "content": "The increase in the frequency of recessive lethal sex-linked mutations induced by fractionated effect of ethylene imine (EI) an ethylmethanesulphonate (EMS) on mature sperm of Drosophila melanogaster was observed and compared uith prolonged treatment (8h) and with the additive effect. This effect of dose fractionation was observed in the case of the treatment of sperms in male gonads and in female spermathecas. The increase of the mutation frequency was noted by brood-pattern method after fractionated treatment of spermatocytes and spermatogonia only with EMS. This increase was not observed under the effect of EI on spermatocytes and spermatogonia because of the high sierilization activity of EI. Possible mechanisms of the effects observed are discussed.", "contents": "[Analysis of mutation frequency following continuous and fractionated application of ethyleneimine and ethyl methanesulfonate to male sex cells of Drosophila melanogaster]. The increase in the frequency of recessive lethal sex-linked mutations induced by fractionated effect of ethylene imine (EI) an ethylmethanesulphonate (EMS) on mature sperm of Drosophila melanogaster was observed and compared uith prolonged treatment (8h) and with the additive effect. This effect of dose fractionation was observed in the case of the treatment of sperms in male gonads and in female spermathecas. The increase of the mutation frequency was noted by brood-pattern method after fractionated treatment of spermatocytes and spermatogonia only with EMS. This increase was not observed under the effect of EI on spermatocytes and spermatogonia because of the high sierilization activity of EI. Possible mechanisms of the effects observed are discussed."}
{"id": "PMID:211072", "title": "[Results of various operations for syndactylia (follow-up studies and statistical evaluation of 101 primary operations)].", "content": "101 cases of syndactyly in 34 male and 14 female infants who were aged three months to seven years at the time of their initial surgery were reviewed one to 9.5 years thereafter. The web space was formed by a palmar and a dorsal flap; in 50% of all commissures the result was found satisfactory in the follow-up series. Straight incision - performed in two thirds of our cases - caused scar contractures and deformities of several fingers. In contrary, zig-zag or wavy incisions showed good results. Using almost exclusively full thickness skin grafts from the arm, the donor site looked poor because of non-cosmetic scares and keloids. After surgery two thirds of all patients used a special splint for finger abduction for an average of about one year; neither an amelioration of insufficient primary surgery was achieved nor reappearance of syndactylism could be avoided by this device. The mobility of joints was partially decreased regardless of the pre-operative condition. Combined functions in grasping, however, were not restricted to a considerable degree. There was no difference between cutaneous and osseous syndactylism with respect to the abduction ability. Even slight impairment of wound healing caused reappearance of syndactylism; reseparation of fingers was necessary 32 times during a ten year period of follow-up. Scar contractures - especially after necrosis of skin grafts and deep infections - required early correction, while slowly developing secondary webs had to be separated some years later. Disturbance of wound healing must, therefore, be treated adequately, or better should be avoided by precise surgery and careful management of postoperative dressing.", "contents": "[Results of various operations for syndactylia (follow-up studies and statistical evaluation of 101 primary operations)]. 101 cases of syndactyly in 34 male and 14 female infants who were aged three months to seven years at the time of their initial surgery were reviewed one to 9.5 years thereafter. The web space was formed by a palmar and a dorsal flap; in 50% of all commissures the result was found satisfactory in the follow-up series. Straight incision - performed in two thirds of our cases - caused scar contractures and deformities of several fingers. In contrary, zig-zag or wavy incisions showed good results. Using almost exclusively full thickness skin grafts from the arm, the donor site looked poor because of non-cosmetic scares and keloids. After surgery two thirds of all patients used a special splint for finger abduction for an average of about one year; neither an amelioration of insufficient primary surgery was achieved nor reappearance of syndactylism could be avoided by this device. The mobility of joints was partially decreased regardless of the pre-operative condition. Combined functions in grasping, however, were not restricted to a considerable degree. There was no difference between cutaneous and osseous syndactylism with respect to the abduction ability. Even slight impairment of wound healing caused reappearance of syndactylism; reseparation of fingers was necessary 32 times during a ten year period of follow-up. Scar contractures - especially after necrosis of skin grafts and deep infections - required early correction, while slowly developing secondary webs had to be separated some years later. Disturbance of wound healing must, therefore, be treated adequately, or better should be avoided by precise surgery and careful management of postoperative dressing."}
{"id": "PMID:211077", "title": "[The motor response potential after distal and proximal stimulation: studies in healthy volunteers and in polyneuropathies (author's transl)].", "content": "Muscle responses evoked distally and proximally were recorded in median and in peroneal nerves from controls and patients with polyneuropathies of different origin. The following parameters were studied in the individual muscle response: 1. the amplitude of the potential, measured peak to peak, 2. the amplitude of the negative phase, 3. the total duration of the potential, 4. the duration of the negative phase, 5. the area covered by the negative phase. Results of the proximal measurements were divided by those of the distal records. Distal motor latencies and nerve conduction velocities were also determined. In controls a loss of amplitude of 10-15% and an equal reduction of the area covered by the negative phase was noted in proximally evoked responses and the duration of the negative phase was increased by 2-7% when compared with distal measurements. In some polyneuropathies these parameters showed significantly pathological changes, although distal motor latency, amplitude and nerve conduction velocity were still within the normal range. Comparison of distally and proximally evoked muscle potentials may thus lead to further information about the mode of conduction in altered motor nerves.", "contents": "[The motor response potential after distal and proximal stimulation: studies in healthy volunteers and in polyneuropathies (author's transl)]. Muscle responses evoked distally and proximally were recorded in median and in peroneal nerves from controls and patients with polyneuropathies of different origin. The following parameters were studied in the individual muscle response: 1. the amplitude of the potential, measured peak to peak, 2. the amplitude of the negative phase, 3. the total duration of the potential, 4. the duration of the negative phase, 5. the area covered by the negative phase. Results of the proximal measurements were divided by those of the distal records. Distal motor latencies and nerve conduction velocities were also determined. In controls a loss of amplitude of 10-15% and an equal reduction of the area covered by the negative phase was noted in proximally evoked responses and the duration of the negative phase was increased by 2-7% when compared with distal measurements. In some polyneuropathies these parameters showed significantly pathological changes, although distal motor latency, amplitude and nerve conduction velocity were still within the normal range. Comparison of distally and proximally evoked muscle potentials may thus lead to further information about the mode of conduction in altered motor nerves."}
{"id": "PMID:211083", "title": "Effect of concurrent cytomegaloviral infection and undernutrition on the growth and immune response of mice.", "content": "Mice were inoculated with murine cytomegalovirus (MCMV) passaged in cell cultures within 24 h of birth and subsequently fed an adequate or a low-protein diet after weaning; increases in body weight, the blastogenic response of lymphocytes to T and B cell mitogens, and the capability to produce antibodies to T or B cell-dependent antigens were observed for the first 28 to 42 days of life. Neonatal infection resulted in immunosuppression and retarded physical growth through the first 4 weeks of life. After weaning (3 weeks), the effect of MCMV infection of well-nourished mice paralleled the effect of undernutrition in uninfected animals. Undernutrition and MCMV infection functioned synergistically.", "contents": "Effect of concurrent cytomegaloviral infection and undernutrition on the growth and immune response of mice. Mice were inoculated with murine cytomegalovirus (MCMV) passaged in cell cultures within 24 h of birth and subsequently fed an adequate or a low-protein diet after weaning; increases in body weight, the blastogenic response of lymphocytes to T and B cell mitogens, and the capability to produce antibodies to T or B cell-dependent antigens were observed for the first 28 to 42 days of life. Neonatal infection resulted in immunosuppression and retarded physical growth through the first 4 weeks of life. After weaning (3 weeks), the effect of MCMV infection of well-nourished mice paralleled the effect of undernutrition in uninfected animals. Undernutrition and MCMV infection functioned synergistically."}
{"id": "PMID:211084", "title": "Antibodies in urine of chimpanzees with chronic adenoviral viruria.", "content": "Many chimpanzees have naturally occurring chronic intermittent viruria with an adenovirus of a new type called Pan 11. Small amounts of neutralizing antibodies to Pan 11 adenovirus were found in the urine of chimpanzees. Urinary antibodies to adenovirus were mainly of the immunoglobulin G (IgG) class with some IgA antibodies also present. There was no neutralizing activity in urine against another adenovirus, Pan 9, which has been isolated from lymph nodes, but not from urine, of chimpanzees; however, sera of all chimpanzees had neutralizing antibodies to Pan 9 virus, some with titers similar to those of antibodies against Pan 11 virus. Antibodies reacting with simian cytomegalovirus by indirect immunofluorescence were found in sera of all chimpanzees tested and in two of six urines. There was no correlation between levels of antiviral IgG antibodies in serum and urine by immunofluorescence. These findings suggest that both IgG and IgA antibodies may be locally produced in response to viral infection of the urinary tract in primates.", "contents": "Antibodies in urine of chimpanzees with chronic adenoviral viruria. Many chimpanzees have naturally occurring chronic intermittent viruria with an adenovirus of a new type called Pan 11. Small amounts of neutralizing antibodies to Pan 11 adenovirus were found in the urine of chimpanzees. Urinary antibodies to adenovirus were mainly of the immunoglobulin G (IgG) class with some IgA antibodies also present. There was no neutralizing activity in urine against another adenovirus, Pan 9, which has been isolated from lymph nodes, but not from urine, of chimpanzees; however, sera of all chimpanzees had neutralizing antibodies to Pan 9 virus, some with titers similar to those of antibodies against Pan 11 virus. Antibodies reacting with simian cytomegalovirus by indirect immunofluorescence were found in sera of all chimpanzees tested and in two of six urines. There was no correlation between levels of antiviral IgG antibodies in serum and urine by immunofluorescence. These findings suggest that both IgG and IgA antibodies may be locally produced in response to viral infection of the urinary tract in primates."}
{"id": "PMID:211085", "title": "Suppression and enhancement of mitogen response in chickens infected with Marek's disease virus and the herpesvirus of turkeys.", "content": "The kinetics of phytohemagglutinin (PHA) response of peripheral blood lymphocytes from chickens infected with oncogenic Marek's disease (MD) virus (MDV) or nononcogenic herpesvirus of turkeys (HVT) was studied with a whole blood microassay. At about 7 days after inoculation, a depression in PHA response was observed in MDV-inoculated resistant line N or susceptible line 7(2) chickens and in HVT-inoculated line 7(2) chickens. All chickens initially regained their PHA responsiveness. Susceptible chickens that died of MD or developed MD lymphoma in later stages of virus infection showed a second severe depression in PHA response. No depression was observed in HVT-vaccinated chickens when challenged with MDV. The PHA response of MDV-inoculated chickens that survived MD, HVT-inoculated chickens, and HVT-vaccinated MDV-challenged chickens showed evidence of enhancement. The depression of PHA response was studied and was attributed to the suppressive effect of macrophages on T-cell response, a finding consistent with our previous studies on MDV suppression of PHA response.", "contents": "Suppression and enhancement of mitogen response in chickens infected with Marek's disease virus and the herpesvirus of turkeys. The kinetics of phytohemagglutinin (PHA) response of peripheral blood lymphocytes from chickens infected with oncogenic Marek's disease (MD) virus (MDV) or nononcogenic herpesvirus of turkeys (HVT) was studied with a whole blood microassay. At about 7 days after inoculation, a depression in PHA response was observed in MDV-inoculated resistant line N or susceptible line 7(2) chickens and in HVT-inoculated line 7(2) chickens. All chickens initially regained their PHA responsiveness. Susceptible chickens that died of MD or developed MD lymphoma in later stages of virus infection showed a second severe depression in PHA response. No depression was observed in HVT-vaccinated chickens when challenged with MDV. The PHA response of MDV-inoculated chickens that survived MD, HVT-inoculated chickens, and HVT-vaccinated MDV-challenged chickens showed evidence of enhancement. The depression of PHA response was studied and was attributed to the suppressive effect of macrophages on T-cell response, a finding consistent with our previous studies on MDV suppression of PHA response."}
{"id": "PMID:211086", "title": "Studies on gonococcus infection. XV. Identification of surface proteins of Neisseria gonorrhoeae correlated with leukocyte association.", "content": "Neisseria gonorrhoeae which exhibit high levels of leukocyte association have a surface protein which is considerably diminished in isogenic gonococci which exhibit low levels of leukocyte association (LA). The LA protein exhibits strain variation in molecular weight and immunogenicity. Membranes derived from LA+ and LA- organisms show quantitative differences in their adsorption to leukocytes; these differences are analogous to those found for the intact organisms regarding their association with leukocytes.", "contents": "Studies on gonococcus infection. XV. Identification of surface proteins of Neisseria gonorrhoeae correlated with leukocyte association. Neisseria gonorrhoeae which exhibit high levels of leukocyte association have a surface protein which is considerably diminished in isogenic gonococci which exhibit low levels of leukocyte association (LA). The LA protein exhibits strain variation in molecular weight and immunogenicity. Membranes derived from LA+ and LA- organisms show quantitative differences in their adsorption to leukocytes; these differences are analogous to those found for the intact organisms regarding their association with leukocytes."}
{"id": "PMID:211087", "title": "Vascular permeability changes in the central nervous system of rats with hyperacute experimental allergic encephalomyelitis induced with the aid of a substance from Bordetella pertussis.", "content": "Development of hyperacute experimental allergic encephalomyelitis in Lewis rats after intraperitoneal administration of a mixture of guinea pig spinal cord emulsion and pertussigen from Bordetella pertussis was accompanied by an increase in vascular permeability in the central nervous system. The increased permeability was most striking in the spinal cord and seemed to be associated with the ascending development of paralysis. Rats that had completely recovered from paralysis did not have any increased permeability in the central nervous system. Rats which developed paralysis after inoculation with either guinea pig spinal cord emulsion alone or with complete Freund adjuvant had only a small degree, if any, of increased permeability in the vascular system of the central nervous system.", "contents": "Vascular permeability changes in the central nervous system of rats with hyperacute experimental allergic encephalomyelitis induced with the aid of a substance from Bordetella pertussis. Development of hyperacute experimental allergic encephalomyelitis in Lewis rats after intraperitoneal administration of a mixture of guinea pig spinal cord emulsion and pertussigen from Bordetella pertussis was accompanied by an increase in vascular permeability in the central nervous system. The increased permeability was most striking in the spinal cord and seemed to be associated with the ascending development of paralysis. Rats that had completely recovered from paralysis did not have any increased permeability in the central nervous system. Rats which developed paralysis after inoculation with either guinea pig spinal cord emulsion alone or with complete Freund adjuvant had only a small degree, if any, of increased permeability in the vascular system of the central nervous system."}
{"id": "PMID:211088", "title": "Immunofluorescence of hepatitis A virus antigen in chimpanzees.", "content": "Chimpanzee liver biopsies and necropsy tissues were examined by immunofluorescence for hepatitis A virus antigen. Results further indicate that the liver may be the sole site of replication for the virus.", "contents": "Immunofluorescence of hepatitis A virus antigen in chimpanzees. Chimpanzee liver biopsies and necropsy tissues were examined by immunofluorescence for hepatitis A virus antigen. Results further indicate that the liver may be the sole site of replication for the virus."}
{"id": "PMID:211089", "title": "Antiviral activity in interferon-treated bovine tracheal organ cultures.", "content": "The effect of bovine interferon on the replication of infectious bovine rhinotracheitis virus and vesicular stomatitis virus in bovine tracheal organ cultures was studied. After treatment of tracheal organ cultures with interferon, inhibition of infectious bovine rhinotracheitis virus and vesicular stomatitis virus replication was observed. This tracheal organ system may be useful in determining the in vivo response to interferon for viral infections of the bovine respiratory tract.", "contents": "Antiviral activity in interferon-treated bovine tracheal organ cultures. The effect of bovine interferon on the replication of infectious bovine rhinotracheitis virus and vesicular stomatitis virus in bovine tracheal organ cultures was studied. After treatment of tracheal organ cultures with interferon, inhibition of infectious bovine rhinotracheitis virus and vesicular stomatitis virus replication was observed. This tracheal organ system may be useful in determining the in vivo response to interferon for viral infections of the bovine respiratory tract."}
{"id": "PMID:211090", "title": "Some properties of beta-toxin produced by Clostridium perfringens type C.", "content": "Purified beta-toxin from Clostridium perfringens type C was found to be a single polypeptide chain protein with a molecular weight of approximately 30,000. The toxin was heat labile, with 75% of its activity being inactivated by incubation at 50 degrees C for 5 min. Biological activity of the purified toxin was completely destroyed on exposure to trypsin for 30 min at 37 degrees C. The 50% lethal dose for mice was 1.87 microgram of purified toxin.", "contents": "Some properties of beta-toxin produced by Clostridium perfringens type C. Purified beta-toxin from Clostridium perfringens type C was found to be a single polypeptide chain protein with a molecular weight of approximately 30,000. The toxin was heat labile, with 75% of its activity being inactivated by incubation at 50 degrees C for 5 min. Biological activity of the purified toxin was completely destroyed on exposure to trypsin for 30 min at 37 degrees C. The 50% lethal dose for mice was 1.87 microgram of purified toxin."}
{"id": "PMID:211091", "title": "Herpes simplex virus type 2 infection of neonatal mice.", "content": "We have demonstrated that newborn mice can be infected orally with herpes simplex virus type 2. Transplacental and transvaginal transmission of herpes simplex virus type 2 did not occur in our mice. Failure to produce natural transvaginal infection in mice may be explained by the relatively short period of exposure to the virus during parturition. These experiments demonstrate that high oral doses of herpes simplex virus type 2 can produce disseminate herpes neonatal infection in mice and therefore may be useful in future investigations into the mechanism and the treatment of this disease.", "contents": "Herpes simplex virus type 2 infection of neonatal mice. We have demonstrated that newborn mice can be infected orally with herpes simplex virus type 2. Transplacental and transvaginal transmission of herpes simplex virus type 2 did not occur in our mice. Failure to produce natural transvaginal infection in mice may be explained by the relatively short period of exposure to the virus during parturition. These experiments demonstrate that high oral doses of herpes simplex virus type 2 can produce disseminate herpes neonatal infection in mice and therefore may be useful in future investigations into the mechanism and the treatment of this disease."}
{"id": "PMID:211092", "title": "E.s.r. and spin-trapping studies of the reactions of hydrated electrons with dipeptides.", "content": "The reactions of hydrated electrons (eaq-) with 55 dipeptides and 25 acetyl and formyl amino acids have been studied by e.s.r. and spin-trapping techniques. Gamma-radiolysis of deaerated aqueous solutions was used to generate eaq-, and sodium formate or t-BuOH was added to scavenge the OH radicals. t-Nitrosobutane was employed as the spin-trapping reagent. The radical,--CO---NH--, which is the initial product of the reactions of eaq- with dipeptides, was observed only for val-gly, val-ala, val-leu and ile-ala. For most of the dipeptides this radical converts to the primary deamination radical, CHR'-CONH-CHR-COO-, where R and R' are the side-chains of the common amino acids. In many cases a radical of the type CHR-COO-, formed by secondary deamination, was also observed. Only secondary deamination reactions were observed for dipeptides containing beta-alanine as the amino terminal residue and for acetyl and formyl amino acids. The secondary deamination reactions of eaq- with dipeptides, acetyl and formyl amino acids in aqueous solutions have not been observed previously. This type of reaction is of interest since it brings about main-chain scission in polypeptides and proteins.", "contents": "E.s.r. and spin-trapping studies of the reactions of hydrated electrons with dipeptides. The reactions of hydrated electrons (eaq-) with 55 dipeptides and 25 acetyl and formyl amino acids have been studied by e.s.r. and spin-trapping techniques. Gamma-radiolysis of deaerated aqueous solutions was used to generate eaq-, and sodium formate or t-BuOH was added to scavenge the OH radicals. t-Nitrosobutane was employed as the spin-trapping reagent. The radical,--CO---NH--, which is the initial product of the reactions of eaq- with dipeptides, was observed only for val-gly, val-ala, val-leu and ile-ala. For most of the dipeptides this radical converts to the primary deamination radical, CHR'-CONH-CHR-COO-, where R and R' are the side-chains of the common amino acids. In many cases a radical of the type CHR-COO-, formed by secondary deamination, was also observed. Only secondary deamination reactions were observed for dipeptides containing beta-alanine as the amino terminal residue and for acetyl and formyl amino acids. The secondary deamination reactions of eaq- with dipeptides, acetyl and formyl amino acids in aqueous solutions have not been observed previously. This type of reaction is of interest since it brings about main-chain scission in polypeptides and proteins."}
{"id": "PMID:211093", "title": "Free radicals in U.V.-irradiated aqueous solutions of substituted amides: an e.s.r. and spin-trapping study.", "content": "The radicals produced by reactions of hydroxyl radicals with alkyl substituted ureas and amides in aqueous solutions have been investigated. Hydroxyl radicals were produced by U.V. photolysis of H2O2 and the short-lived amide and urea radicals were spin-trapped by t-nitrosobutane and identified by e.s.r. For all N-alkyl derivatives of urea and acetamide, and for N,N-dimethyl propionamide and N,N-diethyl formamide, only radicals centred on N-alkyl groups were detected. Radicals situated only on alkyl groups attached to the carbonyl carbon were observed for dimethyl acetamide, trimethyl acetamide and butyramide. However, for N,N-dimethyl butyramide, N, N-diethyl butyramide, N-methyl propionamide and N, N-diethyl propionamide, free radicals were formed which were localized on the alkyl group attached to the amide carbon as well as those attached to nitrogen. The hydrogen atom bound to the carbonyl carbon was abstracted in N-ethyl formamide. Acyl radicals formed by C-N scission due to direct U.V. photolysis of N, N-dimethyl butyramide and N,N-dimethyl propionamide were also detected.", "contents": "Free radicals in U.V.-irradiated aqueous solutions of substituted amides: an e.s.r. and spin-trapping study. The radicals produced by reactions of hydroxyl radicals with alkyl substituted ureas and amides in aqueous solutions have been investigated. Hydroxyl radicals were produced by U.V. photolysis of H2O2 and the short-lived amide and urea radicals were spin-trapped by t-nitrosobutane and identified by e.s.r. For all N-alkyl derivatives of urea and acetamide, and for N,N-dimethyl propionamide and N,N-diethyl formamide, only radicals centred on N-alkyl groups were detected. Radicals situated only on alkyl groups attached to the carbonyl carbon were observed for dimethyl acetamide, trimethyl acetamide and butyramide. However, for N,N-dimethyl butyramide, N, N-diethyl butyramide, N-methyl propionamide and N, N-diethyl propionamide, free radicals were formed which were localized on the alkyl group attached to the amide carbon as well as those attached to nitrogen. The hydrogen atom bound to the carbonyl carbon was abstracted in N-ethyl formamide. Acyl radicals formed by C-N scission due to direct U.V. photolysis of N, N-dimethyl butyramide and N,N-dimethyl propionamide were also detected."}
{"id": "PMID:211094", "title": "E.s.r. study of the post-radiolysis growth of spin-trapped radicals in gamma-irradiated aqueous solutions of thymine.", "content": "The post-irradiation growth of the spin-adduct nitroxide radical produced by the addition of the thymine--OD radical to t-nitrosobutane (tNB) in gamma-irradiated, de-aerated D2O solutions was investigated by e.s.r. The thymine--OD radical was formed by the addition of an OD radical to the C(5) position of thymine. Growth reached a greater maximum value and was more rapid with increasing dose. At a fixed dose, growth was also greater and more rapid if oxygen was present after gamma-radiolysis. The addition of a second radical to the spin-adduct nitroxide during radiolysis to give a diamagnetic intermediate, which can regenerate the spin-adduct radical during storage in air-free and in air-saturated solutions at room temperature, was inferred to be responsible for post-irradiation growth. U.V. photolysis at 260-280 nm of a solution containing the diamagnetic intermediate rapidly regenerates the spin-adduct nitroxide. The longer lifetime of the diamagnetic intermediate in oxygen-free solutions may be relevant to an understanding of the anoxic sensitization by nitroxides in cellular systems.", "contents": "E.s.r. study of the post-radiolysis growth of spin-trapped radicals in gamma-irradiated aqueous solutions of thymine. The post-irradiation growth of the spin-adduct nitroxide radical produced by the addition of the thymine--OD radical to t-nitrosobutane (tNB) in gamma-irradiated, de-aerated D2O solutions was investigated by e.s.r. The thymine--OD radical was formed by the addition of an OD radical to the C(5) position of thymine. Growth reached a greater maximum value and was more rapid with increasing dose. At a fixed dose, growth was also greater and more rapid if oxygen was present after gamma-radiolysis. The addition of a second radical to the spin-adduct nitroxide during radiolysis to give a diamagnetic intermediate, which can regenerate the spin-adduct radical during storage in air-free and in air-saturated solutions at room temperature, was inferred to be responsible for post-irradiation growth. U.V. photolysis at 260-280 nm of a solution containing the diamagnetic intermediate rapidly regenerates the spin-adduct nitroxide. The longer lifetime of the diamagnetic intermediate in oxygen-free solutions may be relevant to an understanding of the anoxic sensitization by nitroxides in cellular systems."}
{"id": "PMID:211099", "title": "Immunoenzymehistochemical demonstration of the binding of low density lipoproteins to cultured human fibroblasts.", "content": "Using as indirect cytochemical immunoperoxidase technique, we were able to demonstrate the binding of low density lipoprotein to cultured human fibroblasts. With this technique, fibroblasts from a patient suffering from homozygous hyperlipoproteinaemia type IIa did not show this binding. The method described here allows study of the localization of unmodified low density lipoproteins binding to cultured fibroblasts.", "contents": "Immunoenzymehistochemical demonstration of the binding of low density lipoproteins to cultured human fibroblasts. Using as indirect cytochemical immunoperoxidase technique, we were able to demonstrate the binding of low density lipoprotein to cultured human fibroblasts. With this technique, fibroblasts from a patient suffering from homozygous hyperlipoproteinaemia type IIa did not show this binding. The method described here allows study of the localization of unmodified low density lipoproteins binding to cultured fibroblasts."}
{"id": "PMID:211100", "title": "ACTH-like immunoreactivity in the gastrin cell. Independent changes in gastrin and ACTH-like immunoreactivity during ontogeny.", "content": "Rat antral gastrin cells have been shown to contain ACTH-like immunoreactivity. Studies on the ontogeny of the antral gastrin cells reveal that these cells start to store gastrin before they contain detectable quantities of ACTH-like immunoreactivity. At no stage studied were duodenal gastrin cells found to contain ACTH-like peptides. The data indicate that the G cells synthetizes and/or releases the two hormonal peptides independently.", "contents": "ACTH-like immunoreactivity in the gastrin cell. Independent changes in gastrin and ACTH-like immunoreactivity during ontogeny. Rat antral gastrin cells have been shown to contain ACTH-like immunoreactivity. Studies on the ontogeny of the antral gastrin cells reveal that these cells start to store gastrin before they contain detectable quantities of ACTH-like immunoreactivity. At no stage studied were duodenal gastrin cells found to contain ACTH-like peptides. The data indicate that the G cells synthetizes and/or releases the two hormonal peptides independently."}
{"id": "PMID:211101", "title": "Catalase positive particles from pig lung. Biochemical preparations and morphological studies.", "content": "In pig lung tissue catalase positive particles (CPs) are abundant especially in type II pneumocytes and in Clara cells. In both cell types they occur as circular, oval or elongated membrane profiles surrounding a moderately electron dense matrix lacking a crystalline core. In Clara cells and in part of type II pneumocytes they are located as individual particles without any evident morphological relation to other cell organelles. In part of type II pneumocytes 5-8 particles are forming a group and their close relation to agranular endoplasmic reticulum cisterns is evident. The particles can be purified from lung homogenates by fractionated pelleting and subsequent rate sedimentation in a sucrose gradient using a zonal rotor. The catalase rich fraction bands in the middle of the gradient whereas cytochrome oxidase and part of the acid phosphatase sediments at its heavy end. A second part of acid phosphatase stays at the light end of the gradient and--according to morphological control--seems to correspond to lamellar bodies of the type II pneumocytes. The purified catalase positive particles do not contain hydroxyacid and D-aminoacid oxidases thought to be characteristic H2O2 producing enzymes of peroxisomal systems. The buoyant density of the particles (d = 1.195 g/cm3) is lower than that of liver peroxisomes. Cytochemical controls of the peroxisomal pellets exhibit the particles partly uniformly filled with reaction product, partly irregularly stained.", "contents": "Catalase positive particles from pig lung. Biochemical preparations and morphological studies. In pig lung tissue catalase positive particles (CPs) are abundant especially in type II pneumocytes and in Clara cells. In both cell types they occur as circular, oval or elongated membrane profiles surrounding a moderately electron dense matrix lacking a crystalline core. In Clara cells and in part of type II pneumocytes they are located as individual particles without any evident morphological relation to other cell organelles. In part of type II pneumocytes 5-8 particles are forming a group and their close relation to agranular endoplasmic reticulum cisterns is evident. The particles can be purified from lung homogenates by fractionated pelleting and subsequent rate sedimentation in a sucrose gradient using a zonal rotor. The catalase rich fraction bands in the middle of the gradient whereas cytochrome oxidase and part of the acid phosphatase sediments at its heavy end. A second part of acid phosphatase stays at the light end of the gradient and--according to morphological control--seems to correspond to lamellar bodies of the type II pneumocytes. The purified catalase positive particles do not contain hydroxyacid and D-aminoacid oxidases thought to be characteristic H2O2 producing enzymes of peroxisomal systems. The buoyant density of the particles (d = 1.195 g/cm3) is lower than that of liver peroxisomes. Cytochemical controls of the peroxisomal pellets exhibit the particles partly uniformly filled with reaction product, partly irregularly stained."}
{"id": "PMID:211102", "title": "[Demonstration of an alkali PAS-effect using periodic acid at low concentration (author's transl)].", "content": "It has been shown that an isolated KOH PAS-effect of epithelial mucosubstances in the colonic mucosae of the rat can be demonstrated also without the conventionally used preliminary oxidation/reduction step. The method is based on the use of strongly diluted periodic acid after previous treatment of tissue sections with ethanolic KOH. As the positive reacting material has been proven to be sensitive against treatment with neuraminidase the modified KOH PAS-reaction should be related to the presence of acylated sialic acid residues in mucosubstances of the colonic mucosae of the rat.", "contents": "[Demonstration of an alkali PAS-effect using periodic acid at low concentration (author's transl)]. It has been shown that an isolated KOH PAS-effect of epithelial mucosubstances in the colonic mucosae of the rat can be demonstrated also without the conventionally used preliminary oxidation/reduction step. The method is based on the use of strongly diluted periodic acid after previous treatment of tissue sections with ethanolic KOH. As the positive reacting material has been proven to be sensitive against treatment with neuraminidase the modified KOH PAS-reaction should be related to the presence of acylated sialic acid residues in mucosubstances of the colonic mucosae of the rat."}
{"id": "PMID:211103", "title": "Organ culture of adult mouse intestine IV. Stimulation of glucose-6-phosphatase in vitro.", "content": "Explants of adult mouse jejunum have been maintained in organ culture with or without fructose added to the medium in order to stimulate the intestinal glucose-6-phosphatase (G-6-Pase). When the fructose is added, at the beginning of the culture, a three-fold increase of G-6-Pase in measured during the first 24 h. If the fructose is added after 24 h of culture, no significant increase of the G-6-Pase is registered in comparison with the controls. Proteins, DNA content and dissacharidase activities are not modified during the culture. Alkaline phosphatase activity presents a twofold increase in the controls and stimulated explants. The ultrastructural localization of the G-6-Pase is not altered during the culture.", "contents": "Organ culture of adult mouse intestine IV. Stimulation of glucose-6-phosphatase in vitro. Explants of adult mouse jejunum have been maintained in organ culture with or without fructose added to the medium in order to stimulate the intestinal glucose-6-phosphatase (G-6-Pase). When the fructose is added, at the beginning of the culture, a three-fold increase of G-6-Pase in measured during the first 24 h. If the fructose is added after 24 h of culture, no significant increase of the G-6-Pase is registered in comparison with the controls. Proteins, DNA content and dissacharidase activities are not modified during the culture. Alkaline phosphatase activity presents a twofold increase in the controls and stimulated explants. The ultrastructural localization of the G-6-Pase is not altered during the culture."}
{"id": "PMID:211104", "title": "Improved method for the histochemical demonstration of glucose-6-phosphatase activity.", "content": "Methodological studies on the histochemical technique for the demonstration of G6Pase activity showed that the occurrence of common artifacts: morphological destruction, extracellular precipitation of reaction product and nuclear staining are dependent on the concentration of lead nitrate, buffer and substrate. By studying the effects of systematic variation of the incubation media on the histochemical reaction optimal concentrations of either of these components were determined. An improved medium containing 3.6 mM lead nitrate, 40 mM tris-maleate buffer, pH 6.5, 10 mM G6P and 300 mM sucrose was used for the study of G6Pase distribution patterns in liver acini of juvenile and adult rats of both sexes and in those of starved adult female rats. The results obtained indicate sex dependent differences in the functional organization of the liver acinus and furthermore demonstrate the rapid functional adaptability of liver parenchyma to changes of the nutritional situation.", "contents": "Improved method for the histochemical demonstration of glucose-6-phosphatase activity. Methodological studies on the histochemical technique for the demonstration of G6Pase activity showed that the occurrence of common artifacts: morphological destruction, extracellular precipitation of reaction product and nuclear staining are dependent on the concentration of lead nitrate, buffer and substrate. By studying the effects of systematic variation of the incubation media on the histochemical reaction optimal concentrations of either of these components were determined. An improved medium containing 3.6 mM lead nitrate, 40 mM tris-maleate buffer, pH 6.5, 10 mM G6P and 300 mM sucrose was used for the study of G6Pase distribution patterns in liver acini of juvenile and adult rats of both sexes and in those of starved adult female rats. The results obtained indicate sex dependent differences in the functional organization of the liver acinus and furthermore demonstrate the rapid functional adaptability of liver parenchyma to changes of the nutritional situation."}
{"id": "PMID:211105", "title": "[Distribution of enzymes in the stereocilia of the ductus epididymis of rats (author's transl)].", "content": "Using unfixed or cryostate sections from aldehyde fixed epididymides of adult rats gamma-glutamyl naphthylamides are hydrolysed in the stereocilia of the principal cells in zone 1A-4B and glycyl-prolyl naphthylamides in those of zone 1B-4A (nomenclature of Reid and Cleland, 1957); this is not the case when other amino acid and peptide naphthylamides are employed. Adenosine triphosphate (ATP) is metabolized by the stereocilia in zone 1a, 2, 3 and 4A and adenosine monophosphate (AMP) in the stereocilia of zone 3-6. With thiamine pyrophosphate (TPP) especially the Golgi apparatus of the principal cells in zone 1B and C, 2 and 3 reacts. In addition ATP, AMP and TPP stain the stereocilia of single epithelial cells outside the zones where all stereocilia react. The AMP pattern allows a further subdivision of zone 3 into 3 A and B. Substrates for the demonstration of alpha- and beta-D-glycosidases, non-specific esterases and alkaline phosphatases are either not hydrolyzed by the stereocilia or the rate of hydrolysis is low.", "contents": "[Distribution of enzymes in the stereocilia of the ductus epididymis of rats (author's transl)]. Using unfixed or cryostate sections from aldehyde fixed epididymides of adult rats gamma-glutamyl naphthylamides are hydrolysed in the stereocilia of the principal cells in zone 1A-4B and glycyl-prolyl naphthylamides in those of zone 1B-4A (nomenclature of Reid and Cleland, 1957); this is not the case when other amino acid and peptide naphthylamides are employed. Adenosine triphosphate (ATP) is metabolized by the stereocilia in zone 1a, 2, 3 and 4A and adenosine monophosphate (AMP) in the stereocilia of zone 3-6. With thiamine pyrophosphate (TPP) especially the Golgi apparatus of the principal cells in zone 1B and C, 2 and 3 reacts. In addition ATP, AMP and TPP stain the stereocilia of single epithelial cells outside the zones where all stereocilia react. The AMP pattern allows a further subdivision of zone 3 into 3 A and B. Substrates for the demonstration of alpha- and beta-D-glycosidases, non-specific esterases and alkaline phosphatases are either not hydrolyzed by the stereocilia or the rate of hydrolysis is low."}
{"id": "PMID:211108", "title": "Enterotoxemia in two foals.", "content": "Two Quarter Horse foals from different premises died from enterotoxemia. Clostridium perfringens toxins alpha and beta were demonstrated in the foal's intestines by mouse protection tests. Clostridium perfringens type C was isolated from the intestines of each foal. Histologic examination revealed hemorrhage, necrosis, and massive numbers of C perfringens.", "contents": "Enterotoxemia in two foals. Two Quarter Horse foals from different premises died from enterotoxemia. Clostridium perfringens toxins alpha and beta were demonstrated in the foal's intestines by mouse protection tests. Clostridium perfringens type C was isolated from the intestines of each foal. Histologic examination revealed hemorrhage, necrosis, and massive numbers of C perfringens."}
{"id": "PMID:211110", "title": "Focal loss of pigment in the Belgian Tervuren dog.", "content": "Hypopigmentation most commonly affecting the face and mouth of the Belgian Tervuren dog was characterized by an absence of melanocytes in the epidermis. Pigment loss usually occurred during young adulthood, and although there was partial repigmentation in some dogs, complete repigmentation did not occur. Treatment with vitamin and mineral supplements was unrewarding. The condition appeared to have some degree of heritability and to be similar to vitiligo in man.", "contents": "Focal loss of pigment in the Belgian Tervuren dog. Hypopigmentation most commonly affecting the face and mouth of the Belgian Tervuren dog was characterized by an absence of melanocytes in the epidermis. Pigment loss usually occurred during young adulthood, and although there was partial repigmentation in some dogs, complete repigmentation did not occur. Treatment with vitamin and mineral supplements was unrewarding. The condition appeared to have some degree of heritability and to be similar to vitiligo in man."}
{"id": "PMID:211113", "title": "Plasma dopamine-beta-hydroxylase in childhood psychosis.", "content": "A previous report suggested that plasma dopamine-beta-hydroxylase (DBH) is elevated in childhood autism. We measured plasma DBH in 15 Children with functional psychosis and in 10 psychotic children with known organic etiology. DBH activity was significantly elevated in the children with functional psychoses and showed a significant correlation with age that is not reported for this age range in normals. It is possible that children with functional psychoses show an abnormal continuation of the rise in plasma DBH activity characteristic of infancy. No differences between children with functional psychoses and children with organic psychoses were found for red blood cell catechol-O-methyl-transferase, plasma monoamine oxidase, or plasma cyclic AMP.", "contents": "Plasma dopamine-beta-hydroxylase in childhood psychosis. A previous report suggested that plasma dopamine-beta-hydroxylase (DBH) is elevated in childhood autism. We measured plasma DBH in 15 Children with functional psychosis and in 10 psychotic children with known organic etiology. DBH activity was significantly elevated in the children with functional psychoses and showed a significant correlation with age that is not reported for this age range in normals. It is possible that children with functional psychoses show an abnormal continuation of the rise in plasma DBH activity characteristic of infancy. No differences between children with functional psychoses and children with organic psychoses were found for red blood cell catechol-O-methyl-transferase, plasma monoamine oxidase, or plasma cyclic AMP."}
{"id": "PMID:211114", "title": "Effects of antipain (a protease inhibitor) on respiration, viability, and excision of pyrimidine dimers in UV-irradiated Escherichia coli cells.", "content": "The protease inhibitor antipain increases the effectiveness of UV irradiation on cessation of respiration and cell killing in Escherichia coli B/r cultures without affecting excision of pyrimidine dimers. The actions are similar to those caused by cyclic AMP in irradiated cultures.", "contents": "Effects of antipain (a protease inhibitor) on respiration, viability, and excision of pyrimidine dimers in UV-irradiated Escherichia coli cells. The protease inhibitor antipain increases the effectiveness of UV irradiation on cessation of respiration and cell killing in Escherichia coli B/r cultures without affecting excision of pyrimidine dimers. The actions are similar to those caused by cyclic AMP in irradiated cultures."}
{"id": "PMID:211115", "title": "Control of biodegradative threonine dehydratase inducibility by cyclic AMP in energy-restricted Escherichia coli.", "content": "To explain the requirement for anaerobic conditions in the induction of biodegradative L-threonine dehydratase in Escherichia coli, Crookes strain, measurements of cyclic AMP (cAMP) were made during aerobic and anaerobic growth and upon an aerobic-to-anaerobic transition. Internal cAMP levels were similar (5 to 10 muM) throughout exponential growth, whether aerobic or anaerobic, but only during anaerobiosis was threonine dehydratase synthesized. When an exponentially growing aerobic culture was made anaerobic, a sharp increase in internal cAMP was noted, reaching 300 muM within 10 min and declining thereafter to normal anaerobic levels. Threonine dehydratase synthesis was detected immediately after the attainment of peak cAMP levels and continued for several generations. A similar pattern but with less accumulation of cAMP and less threonine dehydratase production was also noted upon treatment of an aerobically growing culture with KCN. Pyruvate addition at the time of anaerobic shock severely affected both cAMP accumulation and threonine dehydratase synthesis; however, externally added cAMP could partially counter the pyruvate effect on enzyme synthesis. The conclusion was reached that conditions which resulted in a temporary energy deficit brought about the major accumulation of cAMP, and this elevated level served as a signal for initiation of threonine dehydratase synthesis to supply energy by the nonoxidative degradation of threonine.", "contents": "Control of biodegradative threonine dehydratase inducibility by cyclic AMP in energy-restricted Escherichia coli. To explain the requirement for anaerobic conditions in the induction of biodegradative L-threonine dehydratase in Escherichia coli, Crookes strain, measurements of cyclic AMP (cAMP) were made during aerobic and anaerobic growth and upon an aerobic-to-anaerobic transition. Internal cAMP levels were similar (5 to 10 muM) throughout exponential growth, whether aerobic or anaerobic, but only during anaerobiosis was threonine dehydratase synthesized. When an exponentially growing aerobic culture was made anaerobic, a sharp increase in internal cAMP was noted, reaching 300 muM within 10 min and declining thereafter to normal anaerobic levels. Threonine dehydratase synthesis was detected immediately after the attainment of peak cAMP levels and continued for several generations. A similar pattern but with less accumulation of cAMP and less threonine dehydratase production was also noted upon treatment of an aerobically growing culture with KCN. Pyruvate addition at the time of anaerobic shock severely affected both cAMP accumulation and threonine dehydratase synthesis; however, externally added cAMP could partially counter the pyruvate effect on enzyme synthesis. The conclusion was reached that conditions which resulted in a temporary energy deficit brought about the major accumulation of cAMP, and this elevated level served as a signal for initiation of threonine dehydratase synthesis to supply energy by the nonoxidative degradation of threonine."}
{"id": "PMID:211116", "title": "Effect of membrane-associated f1 bacteriophage coat protein upon the activity of Escherichia coli phosphatidylserine synthetase.", "content": "The effects of insertion of the major coat protein of f1 bacteriophage into Escherichia coli membranes were investigated under conditions allowing in vivo analysis of phosphatidylserine synthesis. An E. coli strain possessing a temperature-sensitive phosphatidylserine decarboxylase was utilized under conditions in which the decarboxylase activity was reduced but nonlethal. The presence of the coat protein in the host membranes inhibits the activity of the phosphatidylserine synthetase and perhaps affects the activity of the phosphatidylserine decarboxylase.", "contents": "Effect of membrane-associated f1 bacteriophage coat protein upon the activity of Escherichia coli phosphatidylserine synthetase. The effects of insertion of the major coat protein of f1 bacteriophage into Escherichia coli membranes were investigated under conditions allowing in vivo analysis of phosphatidylserine synthesis. An E. coli strain possessing a temperature-sensitive phosphatidylserine decarboxylase was utilized under conditions in which the decarboxylase activity was reduced but nonlethal. The presence of the coat protein in the host membranes inhibits the activity of the phosphatidylserine synthetase and perhaps affects the activity of the phosphatidylserine decarboxylase."}
{"id": "PMID:211117", "title": "Induction of cyclic AMP phosphodiesterase in Blastocladiella emersonii and its relation to cyclic AMP metabolism.", "content": "Extracts of vegetative cells of Blastocladiella emersonii contain 5% or less of the cyclic AMP phosphodiesterase activity in zoospore extracts. This difference in activity could be accounted for entirely by an increase in the differential rate of phosphodiesterase synthesis during sporulation, beginning after a lag period of about 60 min and extending for at least an additional 90 min into the 4-h sporulation process. To examine the relation between enzyme synthesis and cyclic nucleotide metabolicm, we determined the substrate specificity of phosphodiesterase synthesized during sporulation and partially purified from zoospores. Zoospore extracts contain two components, separable by gel filtration chromatography, with cyclic AMP phosphodiesterase activity. The larger component accounts for 20% of the total activity and the smaller component for 80%. Both components show essentially an absolute substrate specificity for cyclic AMP among several cyclic purine and cyclic pyrimidine nucleotides tested. Nevertheless, we found no change in the total cyclic AMP content of sporulating cells before, during, or after enzyme activity increased. We speculate that some other component of cyclic AMP metabolism or function limits the rate of cyclic AMP hydrolysis in sporulating cells.", "contents": "Induction of cyclic AMP phosphodiesterase in Blastocladiella emersonii and its relation to cyclic AMP metabolism. Extracts of vegetative cells of Blastocladiella emersonii contain 5% or less of the cyclic AMP phosphodiesterase activity in zoospore extracts. This difference in activity could be accounted for entirely by an increase in the differential rate of phosphodiesterase synthesis during sporulation, beginning after a lag period of about 60 min and extending for at least an additional 90 min into the 4-h sporulation process. To examine the relation between enzyme synthesis and cyclic nucleotide metabolicm, we determined the substrate specificity of phosphodiesterase synthesized during sporulation and partially purified from zoospores. Zoospore extracts contain two components, separable by gel filtration chromatography, with cyclic AMP phosphodiesterase activity. The larger component accounts for 20% of the total activity and the smaller component for 80%. Both components show essentially an absolute substrate specificity for cyclic AMP among several cyclic purine and cyclic pyrimidine nucleotides tested. Nevertheless, we found no change in the total cyclic AMP content of sporulating cells before, during, or after enzyme activity increased. We speculate that some other component of cyclic AMP metabolism or function limits the rate of cyclic AMP hydrolysis in sporulating cells."}
{"id": "PMID:211118", "title": "Cyclic AMP binding proteins and cyclic AMP-dependent protein kinase from Blastocladiella emersonii.", "content": "The stoichiometry of cyclic AMP binding protein to cyclic AMP in sporulating cells of Blastocladiella emersonii and the resistance of protein-bound cyclic AMP to enzyme-catalyzed hydrolysis suggest that the distribution of cyclic AMP between free and protein-bound pools is an important factor in cyclic AMP metabolism. Most but not all of the cyclic AMP binding protein in sporulating cells is associated with a cyclic AMP-dependent protein kinase.", "contents": "Cyclic AMP binding proteins and cyclic AMP-dependent protein kinase from Blastocladiella emersonii. The stoichiometry of cyclic AMP binding protein to cyclic AMP in sporulating cells of Blastocladiella emersonii and the resistance of protein-bound cyclic AMP to enzyme-catalyzed hydrolysis suggest that the distribution of cyclic AMP between free and protein-bound pools is an important factor in cyclic AMP metabolism. Most but not all of the cyclic AMP binding protein in sporulating cells is associated with a cyclic AMP-dependent protein kinase."}
{"id": "PMID:211119", "title": "Cystine reductase in the dimorphic fungus Histoplasma capsulatum.", "content": "Organo-sulfur compounds favor the transition of mycelia of Histoplasma capsulatum to the yeast form (6, 8). Investigation of the role of cystine in the transition revealed that the two phases concentrated this amino acid at comparable rates and that mutants defective in the uptake of cystine were still able to undergo the transition normally. Uptake of cystine is therefore probably not a requirement for transition to or maintenance of the yeast phase. Both phases contained a reduced nicotinamide adenine dinucleotide phosphate-dependent glutathione reductase; but a reduced nicotinamide adenine dinucleotide-dependent cystine reductase was detectable only in the yeast phase. The cystine reductase appeared early in the transition of mycelium to yeast. Treatment of mycelia with p-chloromercuriphenylsulfonic acid, which prevented the transition to yeast, had no effect on cystine uptake but strongly inhibited the cystine reductase. These results suggest that cystine reductase may provide reduced sulfhydryl groups involved in the transition of mycelium to yeast.", "contents": "Cystine reductase in the dimorphic fungus Histoplasma capsulatum. Organo-sulfur compounds favor the transition of mycelia of Histoplasma capsulatum to the yeast form (6, 8). Investigation of the role of cystine in the transition revealed that the two phases concentrated this amino acid at comparable rates and that mutants defective in the uptake of cystine were still able to undergo the transition normally. Uptake of cystine is therefore probably not a requirement for transition to or maintenance of the yeast phase. Both phases contained a reduced nicotinamide adenine dinucleotide phosphate-dependent glutathione reductase; but a reduced nicotinamide adenine dinucleotide-dependent cystine reductase was detectable only in the yeast phase. The cystine reductase appeared early in the transition of mycelium to yeast. Treatment of mycelia with p-chloromercuriphenylsulfonic acid, which prevented the transition to yeast, had no effect on cystine uptake but strongly inhibited the cystine reductase. These results suggest that cystine reductase may provide reduced sulfhydryl groups involved in the transition of mycelium to yeast."}
{"id": "PMID:211120", "title": "Saturation transfer electron spin resonance study on the rotational diffusion of calcium- and magnesium-dependent adenosine triphosphatase in sarcoplasmic reticulum membranes.", "content": "The technique of saturation transfer electron spin resonance has been applied to study the rotational diffusion of spin-labeled Ca2+, Mg2+-dependent ATPase molecules in the membranes of sarcoplasmic reticulum vesicles. Comparison of the present data with those for spin-labeled hemoglobin undergoing isotropic rotation leads to a value of 2 X 10(-4) s for the apparent rotational correlation time at 20 degrees C for the membrane-bound protein. Consideration of the anisotropy of the Brownian rotation of the membrane-bound ATPase suggests that the true correlation time for the expected axial rotation may be somewhat smaller than the apparent value. An Arrhenius plot of the rotational motion shows a break, which is interpreted as indicating the occurrence of a conformational change of the ATPase molecule at about 15 degrees C.", "contents": "Saturation transfer electron spin resonance study on the rotational diffusion of calcium- and magnesium-dependent adenosine triphosphatase in sarcoplasmic reticulum membranes. The technique of saturation transfer electron spin resonance has been applied to study the rotational diffusion of spin-labeled Ca2+, Mg2+-dependent ATPase molecules in the membranes of sarcoplasmic reticulum vesicles. Comparison of the present data with those for spin-labeled hemoglobin undergoing isotropic rotation leads to a value of 2 X 10(-4) s for the apparent rotational correlation time at 20 degrees C for the membrane-bound protein. Consideration of the anisotropy of the Brownian rotation of the membrane-bound ATPase suggests that the true correlation time for the expected axial rotation may be somewhat smaller than the apparent value. An Arrhenius plot of the rotational motion shows a break, which is interpreted as indicating the occurrence of a conformational change of the ATPase molecule at about 15 degrees C."}
{"id": "PMID:211121", "title": "Comparison of calcium-activated, cyclic nucleotide-independent protein kinase and adenosine 3':5'-monophosphate-dependent protein kinase as regards the ability to stimulate glycogen breakdown in vitro.", "content": "A cyclic nucleotide-independent protein kinase, which was produced from its proenzyme upon limited proteolysis by a Ca2+-dependent protease (Takai, Y., Yamamoto, M., Inoue, M., Kishimoto, A., & Nishizuka , Y. (1977) Biochem. Biophys. Res. Commun. 77, 542-550), showed an ability to phosphorylate not only muscle glycogen phosphorylase kinase but also glycogen synthase, resulting in activation and inactivation of the respective enzymes, although the protein kinase was less active than adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase toward glycogen synthase. Available evidence indicates that this new protein kinase shows pleiotropic functions apparently similar to those described for cyclic AMP-dependent protein kinase. Nevertheless, these protein kinases were clearly distinguishable from each other in their response to cyclic nucleotides and susceptibility to protein inhibitor.", "contents": "Comparison of calcium-activated, cyclic nucleotide-independent protein kinase and adenosine 3':5'-monophosphate-dependent protein kinase as regards the ability to stimulate glycogen breakdown in vitro. A cyclic nucleotide-independent protein kinase, which was produced from its proenzyme upon limited proteolysis by a Ca2+-dependent protease (Takai, Y., Yamamoto, M., Inoue, M., Kishimoto, A., & Nishizuka , Y. (1977) Biochem. Biophys. Res. Commun. 77, 542-550), showed an ability to phosphorylate not only muscle glycogen phosphorylase kinase but also glycogen synthase, resulting in activation and inactivation of the respective enzymes, although the protein kinase was less active than adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase toward glycogen synthase. Available evidence indicates that this new protein kinase shows pleiotropic functions apparently similar to those described for cyclic AMP-dependent protein kinase. Nevertheless, these protein kinases were clearly distinguishable from each other in their response to cyclic nucleotides and susceptibility to protein inhibitor."}
{"id": "PMID:211124", "title": "Carbamyl phosphate synthetase of Escherichia coli uses the same diastereomer of adenosine-5'-[2-thiotriphosphate] at both ATP sites.", "content": "Carbamyl phosphate synthetase from Escherichia coli has been shown to use only the A isomer of adenosine-5'-[2-thiotriphosphate] in both the ATPase reaction (MgATP HCO3- leads to MgADP + Pi) and the carbamyl phosphate synthesis reaction (2MgATP + HCO3- + L-glutamine leads to 2MgADP + Pi + carbamyl-P + L-glutamate). The B isomer was less than 5% as reactive. In the reverse reaction, only the A isomer of adenosine-5'-[2-thiotriphosphate] is synthesized from adenosine-5'-[2-thiodiphosphate] and carbamyl-P as determined by 31P NMR and a coupled enzymatic assay with Cd2+- hexokinase. It is therefore proposed that carbamyl phosphate synthetase uses the same diastereomer of MgATP at both ATP sites.", "contents": "Carbamyl phosphate synthetase of Escherichia coli uses the same diastereomer of adenosine-5'-[2-thiotriphosphate] at both ATP sites. Carbamyl phosphate synthetase from Escherichia coli has been shown to use only the A isomer of adenosine-5'-[2-thiotriphosphate] in both the ATPase reaction (MgATP HCO3- leads to MgADP + Pi) and the carbamyl phosphate synthesis reaction (2MgATP + HCO3- + L-glutamine leads to 2MgADP + Pi + carbamyl-P + L-glutamate). The B isomer was less than 5% as reactive. In the reverse reaction, only the A isomer of adenosine-5'-[2-thiotriphosphate] is synthesized from adenosine-5'-[2-thiodiphosphate] and carbamyl-P as determined by 31P NMR and a coupled enzymatic assay with Cd2+- hexokinase. It is therefore proposed that carbamyl phosphate synthetase uses the same diastereomer of MgATP at both ATP sites."}
{"id": "PMID:211125", "title": "Nonspecific effect of m7GMP on protein-RNA interactions.", "content": "Cap analogs m7GMP and m7GDP inhibit binding of eukaryotic initiation factors to reovirus capped mRNA but also inhibit complex formation involving uncapped mRNA or 18 S rRNA. Furthermore, Escherichia coli DNA-dependent RNA polymerase binds 18 S rRNA and this interaction is also blocked by m7GMP. These results indicate that inhibition by cap analogs is not a stringent test for putative cap-specific binding between proteins and mRNA.", "contents": "Nonspecific effect of m7GMP on protein-RNA interactions. Cap analogs m7GMP and m7GDP inhibit binding of eukaryotic initiation factors to reovirus capped mRNA but also inhibit complex formation involving uncapped mRNA or 18 S rRNA. Furthermore, Escherichia coli DNA-dependent RNA polymerase binds 18 S rRNA and this interaction is also blocked by m7GMP. These results indicate that inhibition by cap analogs is not a stringent test for putative cap-specific binding between proteins and mRNA."}
{"id": "PMID:211126", "title": "A novel electron paramagnetic resonance signal of \"oxygenated\" cytochrome c oxidase.", "content": "It had been observed previously that a pair of transient EPR resonances (g = 1.78 and 1.69) appears within less than 5 ms on reoxidation of reduced cytochrome c oxidase by O2. Since the location of other lines that are part of the same signal was not known, the quantity of the paramagnetic species involved, and thus the significance of the observed resonances, remained questionable. We have now found a broad resonance at g = 5 which is obviously associated with those at g = 1.78 and 1.69. The width of the signal (approximately 250 mT) at the observed intensity suggests that it represents a significant fraction of one of the components of the enzyme. The signal disappears within less than 5 ms on addition of cyanide or sulfide but only within several hundred milliseconds after addition of ferrocytochrome c. This behavior suggests that it originates from the a3 component of the enzyme. It is suggested that the species represented in the signal is either identical with or part of what has been named collectively the \"oxygenated\" form and recently described \"activated\" forms of the enzyme. On reoxidation of reduced oxidase with oxygen enriched 90% in 17O, no change of signal shape was seen.", "contents": "A novel electron paramagnetic resonance signal of \"oxygenated\" cytochrome c oxidase. It had been observed previously that a pair of transient EPR resonances (g = 1.78 and 1.69) appears within less than 5 ms on reoxidation of reduced cytochrome c oxidase by O2. Since the location of other lines that are part of the same signal was not known, the quantity of the paramagnetic species involved, and thus the significance of the observed resonances, remained questionable. We have now found a broad resonance at g = 5 which is obviously associated with those at g = 1.78 and 1.69. The width of the signal (approximately 250 mT) at the observed intensity suggests that it represents a significant fraction of one of the components of the enzyme. The signal disappears within less than 5 ms on addition of cyanide or sulfide but only within several hundred milliseconds after addition of ferrocytochrome c. This behavior suggests that it originates from the a3 component of the enzyme. It is suggested that the species represented in the signal is either identical with or part of what has been named collectively the \"oxygenated\" form and recently described \"activated\" forms of the enzyme. On reoxidation of reduced oxidase with oxygen enriched 90% in 17O, no change of signal shape was seen."}
{"id": "PMID:211127", "title": "A rapid method for the purification of extrachromosomal DNA from eukaryotic cells.", "content": "A simple and efficient procedure to purify the low molecular weight extrachromosomal DNA from eukaryotic cells is described. Gentle lysis of cells with urea and sodium dodecyl sulfate in 0.24 M phosphate buffer (pH 6.8) is followed by the removal of high molecular weight bulk DNA by centrifugation. Protein and RNA are removed from the supernatant by hydroxyapatite chromatography in urea/phosphate buffer. Urea is then removed with 0.15 M phosphate buffer and the extrachromosomal DNA, virtually free from protein and RNA,  is finally eluted in 0.5 M phosphate buffer. The procedure allows the recovery of about 99% simian virus 40 (SV40) DNA from infected monkey kidney cells in the extrachromosomal fraction. In normal mouse, monkey, andhuman cells, approximately 1% of total cell DNA appears to be extrachromosomal.", "contents": "A rapid method for the purification of extrachromosomal DNA from eukaryotic cells. A simple and efficient procedure to purify the low molecular weight extrachromosomal DNA from eukaryotic cells is described. Gentle lysis of cells with urea and sodium dodecyl sulfate in 0.24 M phosphate buffer (pH 6.8) is followed by the removal of high molecular weight bulk DNA by centrifugation. Protein and RNA are removed from the supernatant by hydroxyapatite chromatography in urea/phosphate buffer. Urea is then removed with 0.15 M phosphate buffer and the extrachromosomal DNA, virtually free from protein and RNA,  is finally eluted in 0.5 M phosphate buffer. The procedure allows the recovery of about 99% simian virus 40 (SV40) DNA from infected monkey kidney cells in the extrachromosomal fraction. In normal mouse, monkey, andhuman cells, approximately 1% of total cell DNA appears to be extrachromosomal."}
{"id": "PMID:211128", "title": "A K+ transport ATPase in Escherichia coli.", "content": "A K+ -stimulated ATPase in membranes of Escherichia coli has been identified as an activity of the Kdp system, and ATP-driven K+ transport system. Three characteristics support association of the ATPase with the Kdp system: (i) ATPase and Kdp transport are both repressed by growth in media containing high concentrations of K+; (ii) the ATPase and Kdp system accept only K+ as substrate, neither requires Na+ nor accepts Rb+ as a substrate; (iii) the affinity of the ATPase and that of th Kdp system for K+ is similar and is altered by mutations in the structural genes of the Kdp system. Discovery of an ATPase associated with a bacterial transport system suggests functional similarities with the ATP-driven transport systems of animal cells.", "contents": "A K+ transport ATPase in Escherichia coli. A K+ -stimulated ATPase in membranes of Escherichia coli has been identified as an activity of the Kdp system, and ATP-driven K+ transport system. Three characteristics support association of the ATPase with the Kdp system: (i) ATPase and Kdp transport are both repressed by growth in media containing high concentrations of K+; (ii) the ATPase and Kdp system accept only K+ as substrate, neither requires Na+ nor accepts Rb+ as a substrate; (iii) the affinity of the ATPase and that of th Kdp system for K+ is similar and is altered by mutations in the structural genes of the Kdp system. Discovery of an ATPase associated with a bacterial transport system suggests functional similarities with the ATP-driven transport systems of animal cells."}
{"id": "PMID:211130", "title": "Bovine sperm forward motility protein. Partial purification and characterization.", "content": "A protein, present in bovine seminal plasma, initiates forward motility in immature, immotile caput spermatozoa that have been incubated with a cyclic AMP phosphodiesterase inhibitor. An improved motility assay was developed to study this process and the protein involved. This forward motility protein exhibits multiple forms when fractionated on the basis of charge or molecular weight. Molecular sieving in urea or sodium dodecyl sulfate and dithiothreitol results in a single peak of activity which will re-form the larger aggregates in the absence of these agents. The molecular weight of this monomeric motility protein, as estimated from molecular sieving under these dissociating conditions, is 37,500. The forward motility protein can be partially purified by heat treatment, gell chromatography in urea, and affinity chromatography on concanavalin A/agarose. Enzymatic treatments further suggest a glycoprotein nature, i.e. treatment with beta-galactosidase, neuraminidase, alpha-mannosidase, or galactose oxidase reduces its activity by 50%; treatment with trypsin completely abolishes forward motility protein activity. On the basis of concurrent studies on the activity, properties, and distribution of forward motility protein in bovine body fluids, it is suggested that this protein is involved in the development of the capacity for motility as sperm traverse the epididymis.", "contents": "Bovine sperm forward motility protein. Partial purification and characterization. A protein, present in bovine seminal plasma, initiates forward motility in immature, immotile caput spermatozoa that have been incubated with a cyclic AMP phosphodiesterase inhibitor. An improved motility assay was developed to study this process and the protein involved. This forward motility protein exhibits multiple forms when fractionated on the basis of charge or molecular weight. Molecular sieving in urea or sodium dodecyl sulfate and dithiothreitol results in a single peak of activity which will re-form the larger aggregates in the absence of these agents. The molecular weight of this monomeric motility protein, as estimated from molecular sieving under these dissociating conditions, is 37,500. The forward motility protein can be partially purified by heat treatment, gell chromatography in urea, and affinity chromatography on concanavalin A/agarose. Enzymatic treatments further suggest a glycoprotein nature, i.e. treatment with beta-galactosidase, neuraminidase, alpha-mannosidase, or galactose oxidase reduces its activity by 50%; treatment with trypsin completely abolishes forward motility protein activity. On the basis of concurrent studies on the activity, properties, and distribution of forward motility protein in bovine body fluids, it is suggested that this protein is involved in the development of the capacity for motility as sperm traverse the epididymis."}
{"id": "PMID:211132", "title": "Binding of divalent cation to phosphoenzyme of sodium- and potassium-transport adenosine triphosphatase.", "content": "In order to study the action of the divalent cation which is essential for phosphorylation of sodium- and potassium-transport adenosine triphosphatase, magnesium ion, the normal ligand, was replaced with calcium ion, which had properties diffeerent from those of Mg2+, Mn2+, Fe2+, Co2+, Ni2+, or Zn2+. Phosphorylation of the enzyme from ATP at pH 7.4 in the presence of Na+ and Ca2+ yielded a Ca.phosphoenzyme (60% of the maximal level) with a normal rate of dephosphorylation following a chase with unlabeled Ca.ATP (PK = 0.092S-1 at 0 degrees C). In contrast, after a chase by a chelator, namely ethylenediaminetetraacetic acid, 1,2-cyclohexylenedinitrilotetraacetic acid, or ethylene glycol bis-(beta-aminoethyl ether)N,N'-tetraacetic acid, dephosphorylation slowed within 5 s and half of the initial phosphoenzyme remained with a stability about 5-fold greater than normal. Three states of the phosphoenzyme were distinguished according to their relative sensitivity to ADP or to K+ added during a chase. Normally prepared Mg.phosphoenzyme was sensitive to K+ but not to ADP; Ca.phosphoenzyme was sensitive either to ADP or to K+; and the stabilized phosphoenzyme prepared from Ca.phosphoenzyme by addition of a chelator was sensitive neither to ADP nor to K+ nor to both together. Addition of Ca2+ to the stabilized phosphoenzyme restored the reactivity to that of Ca.phosphoenzyme. Addition of Mg2+ to the stabilized phosphoenzyme changed the reactivity to that of Mg.phosphoenzyme. Therefore, this unreactive, stabilized state of the phosphoenzyme appeared to be a divalent cation-free phosphoenzyme. With respect to sensitivity to ouabain, Ca.phosphoenzyme was as sensitive as Mg.phosphoenzyme but calcium-free phosphoenzyme was much less sensitive. It was concluded that the divalent cation required for phosphorylation normally remains tightly bound to the phosphoenzyme and is required for normal reactivity. Calcium ion was almost unique in dissociating relatively easily from the phosphoenzyme. Strontium ion appeared to act similarly to Ca2+.", "contents": "Binding of divalent cation to phosphoenzyme of sodium- and potassium-transport adenosine triphosphatase. In order to study the action of the divalent cation which is essential for phosphorylation of sodium- and potassium-transport adenosine triphosphatase, magnesium ion, the normal ligand, was replaced with calcium ion, which had properties diffeerent from those of Mg2+, Mn2+, Fe2+, Co2+, Ni2+, or Zn2+. Phosphorylation of the enzyme from ATP at pH 7.4 in the presence of Na+ and Ca2+ yielded a Ca.phosphoenzyme (60% of the maximal level) with a normal rate of dephosphorylation following a chase with unlabeled Ca.ATP (PK = 0.092S-1 at 0 degrees C). In contrast, after a chase by a chelator, namely ethylenediaminetetraacetic acid, 1,2-cyclohexylenedinitrilotetraacetic acid, or ethylene glycol bis-(beta-aminoethyl ether)N,N'-tetraacetic acid, dephosphorylation slowed within 5 s and half of the initial phosphoenzyme remained with a stability about 5-fold greater than normal. Three states of the phosphoenzyme were distinguished according to their relative sensitivity to ADP or to K+ added during a chase. Normally prepared Mg.phosphoenzyme was sensitive to K+ but not to ADP; Ca.phosphoenzyme was sensitive either to ADP or to K+; and the stabilized phosphoenzyme prepared from Ca.phosphoenzyme by addition of a chelator was sensitive neither to ADP nor to K+ nor to both together. Addition of Ca2+ to the stabilized phosphoenzyme restored the reactivity to that of Ca.phosphoenzyme. Addition of Mg2+ to the stabilized phosphoenzyme changed the reactivity to that of Mg.phosphoenzyme. Therefore, this unreactive, stabilized state of the phosphoenzyme appeared to be a divalent cation-free phosphoenzyme. With respect to sensitivity to ouabain, Ca.phosphoenzyme was as sensitive as Mg.phosphoenzyme but calcium-free phosphoenzyme was much less sensitive. It was concluded that the divalent cation required for phosphorylation normally remains tightly bound to the phosphoenzyme and is required for normal reactivity. Calcium ion was almost unique in dissociating relatively easily from the phosphoenzyme. Strontium ion appeared to act similarly to Ca2+."}
{"id": "PMID:211133", "title": "The tyrosine free radical in ribonucleotide reductase from Escherichia coli.", "content": "One of the two nonidentical subunits of ribonucleotide reductase from Escherichia coli, protein B2, contains an organic free radical required for enzyme activity. Earlier isotope subtitution experiments (Sj\u00f6berg, B.-M., Reichard, P. Gr\u00e4slund, A., and Ehrenberg, A. (1977) J. Biol. Chem. 252, 536-541) demonstrated that the radical was localized to a tyrosine residue of the enzyme and suggested that the spin density of the radical was centered at the methylene carbon of tyrosine. However, additional isotope substitution experiments now show that the spin density of the radical must be delocalized over the aromatic ring of the tyrosine residue.", "contents": "The tyrosine free radical in ribonucleotide reductase from Escherichia coli. One of the two nonidentical subunits of ribonucleotide reductase from Escherichia coli, protein B2, contains an organic free radical required for enzyme activity. Earlier isotope subtitution experiments (Sj\u00f6berg, B.-M., Reichard, P. Gr\u00e4slund, A., and Ehrenberg, A. (1977) J. Biol. Chem. 252, 536-541) demonstrated that the radical was localized to a tyrosine residue of the enzyme and suggested that the spin density of the radical was centered at the methylene carbon of tyrosine. However, additional isotope substitution experiments now show that the spin density of the radical must be delocalized over the aromatic ring of the tyrosine residue."}
{"id": "PMID:211134", "title": "Effect of the lipid environment on protein motion and enzymatic activity of sarcoplasmic reticulum calcium ATPase.", "content": "In order to investigate the roles of the physical states of phospholipid and protein in the enzymatic behavior of the Ca2+ -ATPase from sarcoplasmic reticulum, we have modified the lipid phase of the enzyme, observed the effects on the enzymatic activity at low temperatures, and correlated these effects with spectroscopic measurements of the rotational motions of both the lipid and protein components. Replacement of the native lipids with dipalmitoyl phosphatidylcholine inhibits ATPase activity and decreases both lipid fluidity, as monitored by EPR spectroscopy on a stearic acid spin label, and protein rotational mobility, as monitored by saturation transfer EPR spectroscopy on the covalently spin-labeled enzyme. Solubilization of the lipid-replaced enzyme with Triton X-100 reverses all three of these effects. Ten millimolar CaCl2 added either to the enzyme associated with the endogenous lipids or to the Triton X-100 soulbilized enzyme inhibits both ATPase activity and protein rotational mobility but has no detectable effect on the lipid mobility. These results are consistent with the proposal that both lipid fluidity and protein rotational mobility are essential for enzymatic activity.", "contents": "Effect of the lipid environment on protein motion and enzymatic activity of sarcoplasmic reticulum calcium ATPase. In order to investigate the roles of the physical states of phospholipid and protein in the enzymatic behavior of the Ca2+ -ATPase from sarcoplasmic reticulum, we have modified the lipid phase of the enzyme, observed the effects on the enzymatic activity at low temperatures, and correlated these effects with spectroscopic measurements of the rotational motions of both the lipid and protein components. Replacement of the native lipids with dipalmitoyl phosphatidylcholine inhibits ATPase activity and decreases both lipid fluidity, as monitored by EPR spectroscopy on a stearic acid spin label, and protein rotational mobility, as monitored by saturation transfer EPR spectroscopy on the covalently spin-labeled enzyme. Solubilization of the lipid-replaced enzyme with Triton X-100 reverses all three of these effects. Ten millimolar CaCl2 added either to the enzyme associated with the endogenous lipids or to the Triton X-100 soulbilized enzyme inhibits both ATPase activity and protein rotational mobility but has no detectable effect on the lipid mobility. These results are consistent with the proposal that both lipid fluidity and protein rotational mobility are essential for enzymatic activity."}
{"id": "PMID:211135", "title": "The role of ATP and divalent cations in the regulation of a cardiac phosphorylase phosphatase (phosphoprotein phosphatase) of Mr = 35,000.", "content": "The effects of ATP and divalent cations on a divalent cation-independent phosphorylase phosphatase of Mr = 35,000 (phosphatase S) purified from canine cardiac muscle have been studied. The enzyme can be rapidly inactivated by ATP or other nucleoside di- and triphosphates and PPi, but not by AMP, adenosine, adenine, Pi, EDTA, ethylene glycol bis(beta-aminoethyl ether)N,N' -tetraacetic acid, 1,10-phenanthroline, or 8-hydroxyquinoline. After removing the inactivating agent, such as ATP or PPi, by gel filtraiton followed by exhaustive dialysis, the inactivated enzyme (apophosphatase S) can be reactivated by preincubating with Mn2+ or Co2+, but not with Mg2+, Ca2+, Ni2+, Zn2+, Fe2+, Cu2+, Ba2+, Hg2+, Pb2+, or Cd2+. The Mn2+ -reactivated enzyme, which is less active than the Co2+ -reactivated enzyme, can be again inactivated by preincubating with ATP. The present findings indicate that phosphatase S contains a tightly bound divalent cation, probably Mn2+, in the active site. ATP and PPi, due to their structural similarity to the phosphoprotein substrate and their ability to chelate metal ions, can readily enter the active site to remove the divalent cation(s) essential for the catalytic function. The present findings also indicate that phosphatase S, a common catalytic subunit of several larger molecular forms of nospecific phosphoprotein phosphatase in cardiac muscle, can exist in two interconvertible forms, a metallized form (active) and a demetallized form (inactive). ATP and metal ions may regulate this class of isozymes by mediating the interconversions.", "contents": "The role of ATP and divalent cations in the regulation of a cardiac phosphorylase phosphatase (phosphoprotein phosphatase) of Mr = 35,000. The effects of ATP and divalent cations on a divalent cation-independent phosphorylase phosphatase of Mr = 35,000 (phosphatase S) purified from canine cardiac muscle have been studied. The enzyme can be rapidly inactivated by ATP or other nucleoside di- and triphosphates and PPi, but not by AMP, adenosine, adenine, Pi, EDTA, ethylene glycol bis(beta-aminoethyl ether)N,N' -tetraacetic acid, 1,10-phenanthroline, or 8-hydroxyquinoline. After removing the inactivating agent, such as ATP or PPi, by gel filtraiton followed by exhaustive dialysis, the inactivated enzyme (apophosphatase S) can be reactivated by preincubating with Mn2+ or Co2+, but not with Mg2+, Ca2+, Ni2+, Zn2+, Fe2+, Cu2+, Ba2+, Hg2+, Pb2+, or Cd2+. The Mn2+ -reactivated enzyme, which is less active than the Co2+ -reactivated enzyme, can be again inactivated by preincubating with ATP. The present findings indicate that phosphatase S contains a tightly bound divalent cation, probably Mn2+, in the active site. ATP and PPi, due to their structural similarity to the phosphoprotein substrate and their ability to chelate metal ions, can readily enter the active site to remove the divalent cation(s) essential for the catalytic function. The present findings also indicate that phosphatase S, a common catalytic subunit of several larger molecular forms of nospecific phosphoprotein phosphatase in cardiac muscle, can exist in two interconvertible forms, a metallized form (active) and a demetallized form (inactive). ATP and metal ions may regulate this class of isozymes by mediating the interconversions."}
{"id": "PMID:211137", "title": "Cross-linking studies of the self-association properties of apo-A-I and apo-A-II from human high density lipoprotein.", "content": "The state of self-association of the apoprotein components of human high density lipoprotein have been studied by use of the cross-linking reagent dimethyl-suberimidate. Analusis of the cross-linked products was carried out by soduim dodecyl sulfate-gel electrophoresis and by agarose column chromatography in 6 M guanidine hydrochloride. Apo-A-I was found to exist as a monomer at low concentration, but associates to tetrameric and pentameric forms at concentrations of 0.5 mg/ml or higher. The self-association was found to be ionic strength-dependent, with association promoted by the presence of salt. Apo-A-II was also found to associate, but the major oligomeric form observed was dimeric (Mr = 34,000), and the association was less dependent on ionic strength than for apo-A-I. Cross-linking in the presence of various concentrations of guanidine hydrochloride showed that apo-A-II self-association persisted at higher concentrations of the denaturant than for apo-A-I. Studies of the effect of temperature demonstrated that the self-association of both proteins was diminished at temperatures above 30 degrees C. Recombination of apo-A-II with phospholipid resulted in the formation of particles which yielded primarily trimers upon cross-linking. This suggests that phospholipid binding causes major reorganization of the self-associated forms of apo-A-II.", "contents": "Cross-linking studies of the self-association properties of apo-A-I and apo-A-II from human high density lipoprotein. The state of self-association of the apoprotein components of human high density lipoprotein have been studied by use of the cross-linking reagent dimethyl-suberimidate. Analusis of the cross-linked products was carried out by soduim dodecyl sulfate-gel electrophoresis and by agarose column chromatography in 6 M guanidine hydrochloride. Apo-A-I was found to exist as a monomer at low concentration, but associates to tetrameric and pentameric forms at concentrations of 0.5 mg/ml or higher. The self-association was found to be ionic strength-dependent, with association promoted by the presence of salt. Apo-A-II was also found to associate, but the major oligomeric form observed was dimeric (Mr = 34,000), and the association was less dependent on ionic strength than for apo-A-I. Cross-linking in the presence of various concentrations of guanidine hydrochloride showed that apo-A-II self-association persisted at higher concentrations of the denaturant than for apo-A-I. Studies of the effect of temperature demonstrated that the self-association of both proteins was diminished at temperatures above 30 degrees C. Recombination of apo-A-II with phospholipid resulted in the formation of particles which yielded primarily trimers upon cross-linking. This suggests that phospholipid binding causes major reorganization of the self-associated forms of apo-A-II."}
{"id": "PMID:211138", "title": "Derivatized silica spheres as immunospecific markers for high resolution labeling in electron microscopy.", "content": "For high resolution labeling of influenza virus cell surface antigens on HeLa cells, an immunospecific marker is used with silica sphere cores of 13--14 nm average diameter. These markers are formed using commercially available silica sphere sols. Two other size ranges are available, 7--8 nm and 22--25 nm. The steps for chemical derivatization are described in detail. Amino and aldehyde functions are covalently introduced onto the sphere surface. Sols of these derivatized silica spheres (DSS) are physicochemically stable and therefore usable for years. Coupling of IgG to DSS followed by permeation chromatography on controlled pore glass results in size-defined immunospecific silica sphere markers (DSS-markers). Saturation labeling of cell surface antigens on HeLa cells on cover slips is obtained with the final sphere concentration of 10(14) DSS-marker/cm3 within 20 min. With usual protective conditions, the marker stability and labeling ability are preserved for months. The visibility and the fine structure of the DSS-marker on cell surfaces are shown by using transmission electron microscopy (TEM) with stereo replicas and ultrathin sections.", "contents": "Derivatized silica spheres as immunospecific markers for high resolution labeling in electron microscopy. For high resolution labeling of influenza virus cell surface antigens on HeLa cells, an immunospecific marker is used with silica sphere cores of 13--14 nm average diameter. These markers are formed using commercially available silica sphere sols. Two other size ranges are available, 7--8 nm and 22--25 nm. The steps for chemical derivatization are described in detail. Amino and aldehyde functions are covalently introduced onto the sphere surface. Sols of these derivatized silica spheres (DSS) are physicochemically stable and therefore usable for years. Coupling of IgG to DSS followed by permeation chromatography on controlled pore glass results in size-defined immunospecific silica sphere markers (DSS-markers). Saturation labeling of cell surface antigens on HeLa cells on cover slips is obtained with the final sphere concentration of 10(14) DSS-marker/cm3 within 20 min. With usual protective conditions, the marker stability and labeling ability are preserved for months. The visibility and the fine structure of the DSS-marker on cell surfaces are shown by using transmission electron microscopy (TEM) with stereo replicas and ultrathin sections."}
{"id": "PMID:211139", "title": "Isolation of rat liver lysosomes by isopycnic centrifugation in a metrizamide gradient.", "content": "A preparation, similar to the light mitochondrial fraction of rat liver (L fraction of de Duve et al, (1955, Biochem. J. 60: 604-617), was subfractionated by isopycnic centrifugation in a metrizamide gradient and the distribution of several marker enzymes was established. The granules were layered at the top or bottom of the gradient. In both cases, as ascertained by the enzyme distributions, the lysosomes are well separated from the peroxisomes. A good separation from mitochondria is obtained only when the L fraction if set down underneath the gradient. Taking into account the analytical centrifugation results, a procedure was devised to purify lysosomes from several grams of liver by centrifugation of an L fraction in a discontinuous metrizamide gradient. By this method, a fraction containing 10--12% of the whole liver lysosomes can be prepared. As inferred from the relative specific activity of marker enzymes, it can be estimated that lysosomes are purified between 66 and 80 times in this fraction. As ascertained by plasma membrane marker enzyme activity, the main contaminant could be the plasma membrane components. However, cytochemical tests for 5'AMPase and for acid phosphatase suggest that a large part of the plasma membrane marker enzyme activity present in the purified lysosome preparation could be associated with the lysosomal membrane. The procedure for the isolation of rat liver lysosomes described in this paper is compared with the already existing methods.", "contents": "Isolation of rat liver lysosomes by isopycnic centrifugation in a metrizamide gradient. A preparation, similar to the light mitochondrial fraction of rat liver (L fraction of de Duve et al, (1955, Biochem. J. 60: 604-617), was subfractionated by isopycnic centrifugation in a metrizamide gradient and the distribution of several marker enzymes was established. The granules were layered at the top or bottom of the gradient. In both cases, as ascertained by the enzyme distributions, the lysosomes are well separated from the peroxisomes. A good separation from mitochondria is obtained only when the L fraction if set down underneath the gradient. Taking into account the analytical centrifugation results, a procedure was devised to purify lysosomes from several grams of liver by centrifugation of an L fraction in a discontinuous metrizamide gradient. By this method, a fraction containing 10--12% of the whole liver lysosomes can be prepared. As inferred from the relative specific activity of marker enzymes, it can be estimated that lysosomes are purified between 66 and 80 times in this fraction. As ascertained by plasma membrane marker enzyme activity, the main contaminant could be the plasma membrane components. However, cytochemical tests for 5'AMPase and for acid phosphatase suggest that a large part of the plasma membrane marker enzyme activity present in the purified lysosome preparation could be associated with the lysosomal membrane. The procedure for the isolation of rat liver lysosomes described in this paper is compared with the already existing methods."}
{"id": "PMID:211140", "title": "Role of Ca++ in virus-induced membrane fusion. Ca++ accumulation and ultrastructural changes induced by Sendai virus in chicken erythrocytes.", "content": "Some of the ultrastructural (freeze-etching technique), morphological, and biochemical effects of Sendai virus interaction with chicken erythrocytes have been studied under fusogenic (in the presence of CaCl2) and nonfusogenic (in the presence of ethyleneglycol-bis-N,N'-tetraacetic acid, [EGTA]) conditions. The following phenomena occur, irrespective of the presence of CaCl2 or EGTA: (a) binding of iodinated virus particles to chicken erythrocytes at 4 degrees C and their partial release from the cells at 37 degrees C; (b) gradual incorporation of the viral envelope and viral M-protein into plasma membrane, as visualized in the protoplasmic and exoplasmic fracture (P and E, respectively) faces of the membrane; and (c) virus-dependent transient clustering of intramembrane particles at 4 degrees C, which is reversible after transferring the cells back to 37 degrees C. The following virus-induced phenomena occur only in the presence of CaCl2: (a) rounding of cells followed by their fusion; (b) transient decrease in the density of intramembrane particles; and (c) the virus induces uptake of 45CaCl2 by chicken erythrocytes. The uptake is specific as it is inhibited by LaCl3, and no accumulation of [14C]glucose-1-phosphate ([14C]G-1-P) could be observed under the 45 CaCl2 uptake conditions. The data show that fusion of virus with plasma membrane is a Ca++-independent process and, as such, it should be distinguished from the virus-induced membrane-membrane and cell fusion processes. The latter is absolutely dependent on the rise of intracellular Ca++, as reflected by the fact that Ca++-induced rounding of chicken erythrocytes always precedes fusion (Volsky, D. and A. Loyter. 1977.Biochim. Biophys. Acta 471:253--259).", "contents": "Role of Ca++ in virus-induced membrane fusion. Ca++ accumulation and ultrastructural changes induced by Sendai virus in chicken erythrocytes. Some of the ultrastructural (freeze-etching technique), morphological, and biochemical effects of Sendai virus interaction with chicken erythrocytes have been studied under fusogenic (in the presence of CaCl2) and nonfusogenic (in the presence of ethyleneglycol-bis-N,N'-tetraacetic acid, [EGTA]) conditions. The following phenomena occur, irrespective of the presence of CaCl2 or EGTA: (a) binding of iodinated virus particles to chicken erythrocytes at 4 degrees C and their partial release from the cells at 37 degrees C; (b) gradual incorporation of the viral envelope and viral M-protein into plasma membrane, as visualized in the protoplasmic and exoplasmic fracture (P and E, respectively) faces of the membrane; and (c) virus-dependent transient clustering of intramembrane particles at 4 degrees C, which is reversible after transferring the cells back to 37 degrees C. The following virus-induced phenomena occur only in the presence of CaCl2: (a) rounding of cells followed by their fusion; (b) transient decrease in the density of intramembrane particles; and (c) the virus induces uptake of 45CaCl2 by chicken erythrocytes. The uptake is specific as it is inhibited by LaCl3, and no accumulation of [14C]glucose-1-phosphate ([14C]G-1-P) could be observed under the 45 CaCl2 uptake conditions. The data show that fusion of virus with plasma membrane is a Ca++-independent process and, as such, it should be distinguished from the virus-induced membrane-membrane and cell fusion processes. The latter is absolutely dependent on the rise of intracellular Ca++, as reflected by the fact that Ca++-induced rounding of chicken erythrocytes always precedes fusion (Volsky, D. and A. Loyter. 1977.Biochim. Biophys. Acta 471:253--259)."}
{"id": "PMID:211141", "title": "Effects of two blood culture anticoagulants on growth of Neisseria meningitidis.", "content": "Tests of 25 strains of Neisseria meningitidis for sensitivity to sodium polyanethol sulfonate (SPS) showed that the sensitivity of strains varied with both inoculum size and SPS concentration. In Trypticase soy broth (TSB), 2 out of 13 strains were sensitive to 0.05% SPS, whereas 8 out of 13 strains were sensitive to the same concentration of SPS in brain heart infusion (BHI). In artificial blood cultures with six strains of meningococci, the addition of 10% defibrinated blood was found to eliminate the sensitivity of all six strains to SPS in BHI, but not of the two strains in TSB. Addition of 1.2% gelatin to artificial blood cultures eliminated the inhibitory effect of 0.05% SPS, whereas the addition of 1% yeast extract to blood cultures containing 0.025% or 0.05% SPS enhanced the inhibitory effect of this anticoagulant. None of the 13 strains tested was inhibited by 0.05% sodium amylosulfate in TSB or BHI alone or in artificial blood cultures with these media.", "contents": "Effects of two blood culture anticoagulants on growth of Neisseria meningitidis. Tests of 25 strains of Neisseria meningitidis for sensitivity to sodium polyanethol sulfonate (SPS) showed that the sensitivity of strains varied with both inoculum size and SPS concentration. In Trypticase soy broth (TSB), 2 out of 13 strains were sensitive to 0.05% SPS, whereas 8 out of 13 strains were sensitive to the same concentration of SPS in brain heart infusion (BHI). In artificial blood cultures with six strains of meningococci, the addition of 10% defibrinated blood was found to eliminate the sensitivity of all six strains to SPS in BHI, but not of the two strains in TSB. Addition of 1.2% gelatin to artificial blood cultures eliminated the inhibitory effect of 0.05% SPS, whereas the addition of 1% yeast extract to blood cultures containing 0.025% or 0.05% SPS enhanced the inhibitory effect of this anticoagulant. None of the 13 strains tested was inhibited by 0.05% sodium amylosulfate in TSB or BHI alone or in artificial blood cultures with these media."}
{"id": "PMID:211142", "title": "Detection of Clostridium perfringens enterotoxin in human fecal samples and anti-enterotoxin in sera.", "content": "By using counterimmunoelectrophoresis (CIEP), Clostridium perfringens enterotoxin was successfully demonstrated in fecal samples collected within 1 day of attack from sick individuals involved in a bacteriologically and epidemiologically proven outbreak of C. perfringens food poisoning. In contrast, enterotoxin was not demonstrable in fecal samples of apparently healthy individuals both at high- and low-risk exposure to the organism and enterotoxin or in fecal samples collected 4 to 5 days after a food poisoning outbreak. A 100% prevalence of C. perfringens anti-enterotoxin in sera of human volunteers at high- as well as low-risk exposure to the organism and enterotoxin was recorded with CIEP.", "contents": "Detection of Clostridium perfringens enterotoxin in human fecal samples and anti-enterotoxin in sera. By using counterimmunoelectrophoresis (CIEP), Clostridium perfringens enterotoxin was successfully demonstrated in fecal samples collected within 1 day of attack from sick individuals involved in a bacteriologically and epidemiologically proven outbreak of C. perfringens food poisoning. In contrast, enterotoxin was not demonstrable in fecal samples of apparently healthy individuals both at high- and low-risk exposure to the organism and enterotoxin or in fecal samples collected 4 to 5 days after a food poisoning outbreak. A 100% prevalence of C. perfringens anti-enterotoxin in sera of human volunteers at high- as well as low-risk exposure to the organism and enterotoxin was recorded with CIEP."}
{"id": "PMID:211143", "title": "Comparison of WI-38, MRC-5, and IMR-90 cell strains for isolation of viruses from clinical specimens.", "content": "With the diminishing supply of the human fetal lung WI-38 cell strain, a replacement for viral isolation is needed. Two candidates are the human fetal lung strains MRC-5 and IMR-90. A comparison of WI-38, MRC-5, and IMR-90 was performed to evaluate efficiency and speed of viral isolation, clarity of cytophatic effect, and ease of growing the cells. The inocula were clinical specimens rather than tissue culture-adapted isolates. Frozen samples of 46 specimens that had previously yielded an isolate on WI-38 were thawed and inoculated onto WI-38, MRC-5, and IMR-90 cells. In addition, 95 freshly taken clinical specimens uf undetermined infectivity were inoculated onto the cell strains. Viral recovery rates were similar on all three strains, as were the appearance and speed of onset of the cytophatic effect. MRC-5 and WI-38 cells remained healthy until generation 36, whereas IMR-90 cells went into crisis by generation 20. The longer life span of the MRC-5 cells makes them more suitable than IMR-90 cells to replace the WI-38 strain for routine use in viral diagnosis.", "contents": "Comparison of WI-38, MRC-5, and IMR-90 cell strains for isolation of viruses from clinical specimens. With the diminishing supply of the human fetal lung WI-38 cell strain, a replacement for viral isolation is needed. Two candidates are the human fetal lung strains MRC-5 and IMR-90. A comparison of WI-38, MRC-5, and IMR-90 was performed to evaluate efficiency and speed of viral isolation, clarity of cytophatic effect, and ease of growing the cells. The inocula were clinical specimens rather than tissue culture-adapted isolates. Frozen samples of 46 specimens that had previously yielded an isolate on WI-38 were thawed and inoculated onto WI-38, MRC-5, and IMR-90 cells. In addition, 95 freshly taken clinical specimens uf undetermined infectivity were inoculated onto the cell strains. Viral recovery rates were similar on all three strains, as were the appearance and speed of onset of the cytophatic effect. MRC-5 and WI-38 cells remained healthy until generation 36, whereas IMR-90 cells went into crisis by generation 20. The longer life span of the MRC-5 cells makes them more suitable than IMR-90 cells to replace the WI-38 strain for routine use in viral diagnosis."}
{"id": "PMID:211144", "title": "Incidence and significance of hepatitis B e antigen and antibody in postnecrotic cirrhosis and primary hepatocellular carcinoma.", "content": "A study of the serological markers of Hepatitis B virus (HBV) including e antigen (HBe Ag) and antibody against HBe Ag (anti-HBe) was performed in Senegalese patients suffering from cirrhosis and primary hepatocellular carcinoma, and in a control group (blood donors). It was not possible to diagnose additional HBV infections in primary hepatocellular carcinoma patients using HBe Ag or anti-HBe Ab alone as serological markers. The lower prevalence of HBe Ag among primary hepatocellular carcinoma patients as compared with cirrhotic patients suggests that active replication of HBV becomes increasingly defective during the course of the malignant process.", "contents": "Incidence and significance of hepatitis B e antigen and antibody in postnecrotic cirrhosis and primary hepatocellular carcinoma. A study of the serological markers of Hepatitis B virus (HBV) including e antigen (HBe Ag) and antibody against HBe Ag (anti-HBe) was performed in Senegalese patients suffering from cirrhosis and primary hepatocellular carcinoma, and in a control group (blood donors). It was not possible to diagnose additional HBV infections in primary hepatocellular carcinoma patients using HBe Ag or anti-HBe Ab alone as serological markers. The lower prevalence of HBe Ag among primary hepatocellular carcinoma patients as compared with cirrhotic patients suggests that active replication of HBV becomes increasingly defective during the course of the malignant process."}
{"id": "PMID:211145", "title": "The regulation of skeletal muscle alanine and glutamine formation and release in experimental chronic uremia in the rat: subsensitivity of adenylate cyclase and amino acid release to epinephrine and serotonin.", "content": "The mechanism of the increased alanine and glutamine formation and release from skeletal muscle in experimental uremia was investigated using epitrochlearis preparations from control and chronically uremic rats. In uremic muscle, insensitivity to epinephrine or serotonin suppression of alanine and glutamine release was observed. With control muscles, 1 nm or greater, epinephrine inhibited alanine and glutamine release, whereas with uremic muscles, epinephrine concentrations <1 muM did not alter amino acid release. Decreased alanine and glutamine release with 1 nM serotonin was observed in control muscles, but no inhibition was observed with concentrations <1 muM in uremic muscle. Muscle amino acid levels were the same in control and uremic muscles in the presence or absence of epinephrine or serotonin. The reutilization of released alanine by protein synthesis or oxidation to CO(2) was not differentially affected by epinephrine in uremic muscles as compared with control muscle. Dibutyryl-cAMP inhibited amino acid release equally in uremic and control muscles. Epinephrine or serotonin increased cAMP levels two- to four-fold or more in control than in uremic muscle. Basal- and fluoride-stimulated adenylate cyclase activities were equal in uremic and control muscle homogenates and in membrane fractions, but 10 muM epinephrine-stimulated adenylate cyclase was reduced 30-60% with uremia. At any concentration of epinephrine (0.001-100 muM), the stimulation of membrane adenylate cyclase activity was one- to twofold greater with control membranes than with uremic muscle membranes. With either control or uremic muscle, peak adenylate cyclase activity was observed at 1 muM epinephrine. These data indicate that skeletal muscle in chronic uremia acquires an insensitivity to the metabolic action of epinephrine or serotonin. This insensitivity may be attributable in part to the diminished increments in muscle cAMP levels produced by adrenergic and serotonergic agonists. The decreased cAMP levels may derive in turn from a decreased activity or subsensitization of the agonist-stimulated adenylate cyclase in uremic muscle.", "contents": "The regulation of skeletal muscle alanine and glutamine formation and release in experimental chronic uremia in the rat: subsensitivity of adenylate cyclase and amino acid release to epinephrine and serotonin. The mechanism of the increased alanine and glutamine formation and release from skeletal muscle in experimental uremia was investigated using epitrochlearis preparations from control and chronically uremic rats. In uremic muscle, insensitivity to epinephrine or serotonin suppression of alanine and glutamine release was observed. With control muscles, 1 nm or greater, epinephrine inhibited alanine and glutamine release, whereas with uremic muscles, epinephrine concentrations <1 muM did not alter amino acid release. Decreased alanine and glutamine release with 1 nM serotonin was observed in control muscles, but no inhibition was observed with concentrations <1 muM in uremic muscle. Muscle amino acid levels were the same in control and uremic muscles in the presence or absence of epinephrine or serotonin. The reutilization of released alanine by protein synthesis or oxidation to CO(2) was not differentially affected by epinephrine in uremic muscles as compared with control muscle. Dibutyryl-cAMP inhibited amino acid release equally in uremic and control muscles. Epinephrine or serotonin increased cAMP levels two- to four-fold or more in control than in uremic muscle. Basal- and fluoride-stimulated adenylate cyclase activities were equal in uremic and control muscle homogenates and in membrane fractions, but 10 muM epinephrine-stimulated adenylate cyclase was reduced 30-60% with uremia. At any concentration of epinephrine (0.001-100 muM), the stimulation of membrane adenylate cyclase activity was one- to twofold greater with control membranes than with uremic muscle membranes. With either control or uremic muscle, peak adenylate cyclase activity was observed at 1 muM epinephrine. These data indicate that skeletal muscle in chronic uremia acquires an insensitivity to the metabolic action of epinephrine or serotonin. This insensitivity may be attributable in part to the diminished increments in muscle cAMP levels produced by adrenergic and serotonergic agonists. The decreased cAMP levels may derive in turn from a decreased activity or subsensitization of the agonist-stimulated adenylate cyclase in uremic muscle."}
{"id": "PMID:211147", "title": "Urinary excretion of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate in malignancy.", "content": "The urinary excretion of cyclic adenosine 3',5'-monophosphate (cAMP), corrected for urinary creatinine, was determined in 177 patients with primary or metastatic tumours and in 149 normal subjects. In 26 patients with malignancy and in 10 control subjects the excretion of cyclic guanosine 3',5'-monophosphate (cGMP) was also evaluated. The urinary cAMP/Cr ratio in human neoplasms of epithelial origin was often significantly lower than normal, irrespective of the extension of malignancy. Surgical resection of the tumour, radiotherapy, or theophylline treatment increased urinary excretion of the nucleotide. In patients with malignancy, intravenous infusion of glucagon failed to produce the degree of elevation of plasma cAMP seen in normal subjects. Urines from patients with malignant neoplasms had low values of cAMP/Cr ratio with increased values of cGMP/Cr ratio. These findings could be the result of systemic alteration in synthesis or breakdown of the nucleotides.", "contents": "Urinary excretion of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate in malignancy. The urinary excretion of cyclic adenosine 3',5'-monophosphate (cAMP), corrected for urinary creatinine, was determined in 177 patients with primary or metastatic tumours and in 149 normal subjects. In 26 patients with malignancy and in 10 control subjects the excretion of cyclic guanosine 3',5'-monophosphate (cGMP) was also evaluated. The urinary cAMP/Cr ratio in human neoplasms of epithelial origin was often significantly lower than normal, irrespective of the extension of malignancy. Surgical resection of the tumour, radiotherapy, or theophylline treatment increased urinary excretion of the nucleotide. In patients with malignancy, intravenous infusion of glucagon failed to produce the degree of elevation of plasma cAMP seen in normal subjects. Urines from patients with malignant neoplasms had low values of cAMP/Cr ratio with increased values of cGMP/Cr ratio. These findings could be the result of systemic alteration in synthesis or breakdown of the nucleotides."}
{"id": "PMID:211148", "title": "Localization of receptors for the dipsogenic action of angiotensin II in the subfornical organ of rat.", "content": "The proposal of the subfornical organ (SFO) as a site of receptors for drinking induced by angiotensin II (AII) was investigated with several mutually confirmatory experiments. Intracranial injections of physiological doses of AII elicited drinking if and only if applied directly to the SFO (Experiment I). Ablation of the SFO selectively (Experiment 2) and permanently (Experiment 4) eliminated drinking elicited by physiological doses of intravenously infused AII. Animals in which SFO had been ablated responded normally to cellular dehydration but reduced responding to the extracellular thirsts of beta-adrenergic activation and hyperoncotic colloid dialysis (Experiment 3). Infusion of saralasin, an AII antagonist, directly into the SFO selectively and reversibly antagonized intravenous AII drinking (Experiment 5). The hypothesis that the SFO contains dipsogenic receptors for circulating AII is strongly supported.", "contents": "Localization of receptors for the dipsogenic action of angiotensin II in the subfornical organ of rat. The proposal of the subfornical organ (SFO) as a site of receptors for drinking induced by angiotensin II (AII) was investigated with several mutually confirmatory experiments. Intracranial injections of physiological doses of AII elicited drinking if and only if applied directly to the SFO (Experiment I). Ablation of the SFO selectively (Experiment 2) and permanently (Experiment 4) eliminated drinking elicited by physiological doses of intravenously infused AII. Animals in which SFO had been ablated responded normally to cellular dehydration but reduced responding to the extracellular thirsts of beta-adrenergic activation and hyperoncotic colloid dialysis (Experiment 3). Infusion of saralasin, an AII antagonist, directly into the SFO selectively and reversibly antagonized intravenous AII drinking (Experiment 5). The hypothesis that the SFO contains dipsogenic receptors for circulating AII is strongly supported."}
{"id": "PMID:211146", "title": "Adenosine triphosphatases of rat pancreatic islets: comparison with those of rat kidney.", "content": "Electrolyte fluxes are fundamental to normal endocrine pancreatic function. Adenosine triphosphatases (ATPases) are enzyme systems believed to modulate electrolyte movements across membranes in a number of cell types. This study was undertaken to measure cation-dependent ATPases of rat pancreatic islets. In addition, we compared effects of substances which influence endocrine pancreatic function upon ATPases in homogenates of islets and kidney, the latter being a tissue which would not be expected to have a stimulus-secretion response to substances which activate islets. Both tissues were generally similar with respect to apparent Michaelis constant (ATP) of Na(+)K(+)ATPase, Mg(++)ATPase, and Ca(++)ATPase. In islets and kidney, Na(+)K(+)ATPase specific activity was increased when the Na:K ratio was lowered from 250:1 (175:0.7 mM) to 5:1 (100:20 mM). Inhibition of Na(+)K(+)ATPase at either Na:K ratio by ouabain, an activator of secretion, and enhancement of the high-ratio Na(+)K(+)ATPase by diphenylhydantoin, an islet secretory inhibitor, were also common to both tissues. Because both inhibition and enhancement of Na(+)K(+)ATPase could be studied at the high Na:K ratio, we examined the effect of regulators of secretion upon the activity of this enzyme. Like ouabain, substances which induce or support islet secretion, glucose 16 mM or 3.3 mM, arginine 14.2 mM (with 3.3 mM glucose), or Ca(++) 1 mM, inhibited high-ratio islet Na(+)K(+)ATPase. Like diphenylhydantoin, the inhibitors of insulin secretion, diazoxide 0.22 mM, or NH(4)Cl 16 mM, enhanced this islet ATPase. Neither valine, which is non-secretogenic, nor arginine without glucose, which is a weak secretagogue, had any effect upon islet Na(+)K(+)ATPase. We examined the effect of these substances upon other cation-dependent islet ATPases. Ca(++) inhibited Mg(++)ATPase, and glucose inhibited Ca(++)ATPase. Leucine, 22.9 mM, which induces insulin secretion in the absence of glucose, suppressed islet Ca(++)ATPase and had no effect upon high-ratio Na(+)K(+)ATPase. In contrast to the observations in the islets, most substances which influence islet function had no effect on kidney ATPases, or effects which were different from those seen in islets. Except for ouabain, none of these substances influenced the three kidney ATPases in a manner similar to that seen with islets. These findings support the hypothesis that cation-dependent ATPases are involved in specificity of islet response to substances which influence endocrine pancreatic activity.", "contents": "Adenosine triphosphatases of rat pancreatic islets: comparison with those of rat kidney. Electrolyte fluxes are fundamental to normal endocrine pancreatic function. Adenosine triphosphatases (ATPases) are enzyme systems believed to modulate electrolyte movements across membranes in a number of cell types. This study was undertaken to measure cation-dependent ATPases of rat pancreatic islets. In addition, we compared effects of substances which influence endocrine pancreatic function upon ATPases in homogenates of islets and kidney, the latter being a tissue which would not be expected to have a stimulus-secretion response to substances which activate islets. Both tissues were generally similar with respect to apparent Michaelis constant (ATP) of Na(+)K(+)ATPase, Mg(++)ATPase, and Ca(++)ATPase. In islets and kidney, Na(+)K(+)ATPase specific activity was increased when the Na:K ratio was lowered from 250:1 (175:0.7 mM) to 5:1 (100:20 mM). Inhibition of Na(+)K(+)ATPase at either Na:K ratio by ouabain, an activator of secretion, and enhancement of the high-ratio Na(+)K(+)ATPase by diphenylhydantoin, an islet secretory inhibitor, were also common to both tissues. Because both inhibition and enhancement of Na(+)K(+)ATPase could be studied at the high Na:K ratio, we examined the effect of regulators of secretion upon the activity of this enzyme. Like ouabain, substances which induce or support islet secretion, glucose 16 mM or 3.3 mM, arginine 14.2 mM (with 3.3 mM glucose), or Ca(++) 1 mM, inhibited high-ratio islet Na(+)K(+)ATPase. Like diphenylhydantoin, the inhibitors of insulin secretion, diazoxide 0.22 mM, or NH(4)Cl 16 mM, enhanced this islet ATPase. Neither valine, which is non-secretogenic, nor arginine without glucose, which is a weak secretagogue, had any effect upon islet Na(+)K(+)ATPase. We examined the effect of these substances upon other cation-dependent islet ATPases. Ca(++) inhibited Mg(++)ATPase, and glucose inhibited Ca(++)ATPase. Leucine, 22.9 mM, which induces insulin secretion in the absence of glucose, suppressed islet Ca(++)ATPase and had no effect upon high-ratio Na(+)K(+)ATPase. In contrast to the observations in the islets, most substances which influence islet function had no effect on kidney ATPases, or effects which were different from those seen in islets. Except for ouabain, none of these substances influenced the three kidney ATPases in a manner similar to that seen with islets. These findings support the hypothesis that cation-dependent ATPases are involved in specificity of islet response to substances which influence endocrine pancreatic activity."}
{"id": "PMID:211157", "title": "Receptors for luteinizing hormone-releasing hormone.", "content": "Antisera to luteinizing hormone-releasing hormone (LH-RH) confer on Araldite sections of occasional rat pituitaries moderate immunocytochemical staining to the large secretory granules of gonadotrophs. Treatment of the sections with LH-RH before anti-LH-RH yields strong staining in all animals, irrespective of presence or absence of staining without pretreatment. This enhancement of staining is specific for LH-RH and is a high affinity, saturable reaction. Staining with or without LH-RH pretreatment is absent when anti-LH-RH absorbed with insolubilized LH-RH is used. Staining is inhibited by carboxyterminally-deficient LH-RH, unaffected by aminoterminally deficient LH-RH.", "contents": "Receptors for luteinizing hormone-releasing hormone. Antisera to luteinizing hormone-releasing hormone (LH-RH) confer on Araldite sections of occasional rat pituitaries moderate immunocytochemical staining to the large secretory granules of gonadotrophs. Treatment of the sections with LH-RH before anti-LH-RH yields strong staining in all animals, irrespective of presence or absence of staining without pretreatment. This enhancement of staining is specific for LH-RH and is a high affinity, saturable reaction. Staining with or without LH-RH pretreatment is absent when anti-LH-RH absorbed with insolubilized LH-RH is used. Staining is inhibited by carboxyterminally-deficient LH-RH, unaffected by aminoterminally deficient LH-RH."}
{"id": "PMID:211158", "title": "Adrenal luteinizing hormone releasing hormone receptors.", "content": "Paraffin sections of mouse adrenals processed with antiserum to luteinizing hormone-releasing hormone (LHRH) in the unlabeled antibody enzyme method reveal moderate staining in the cytoplasm of cells of zona fasciculata and reticularis. The stain is intensified upon pretreatment of sections with LHRH. Pretreated sections processed with solid phase immunoabsorbed LHRH are unstained. Analogues of LHRH deficient in the C-terminal glycine amide inhibit staining, while analogues deficient in the N-terminal pyroglutamic acid have no effect. It is concluded that the adrenal contains receptors for a ligand resembling LHRH in receptor and immunoreactivity. The possibility is considered that the ligand may be an inhibitor of pineal origin.", "contents": "Adrenal luteinizing hormone releasing hormone receptors. Paraffin sections of mouse adrenals processed with antiserum to luteinizing hormone-releasing hormone (LHRH) in the unlabeled antibody enzyme method reveal moderate staining in the cytoplasm of cells of zona fasciculata and reticularis. The stain is intensified upon pretreatment of sections with LHRH. Pretreated sections processed with solid phase immunoabsorbed LHRH are unstained. Analogues of LHRH deficient in the C-terminal glycine amide inhibit staining, while analogues deficient in the N-terminal pyroglutamic acid have no effect. It is concluded that the adrenal contains receptors for a ligand resembling LHRH in receptor and immunoreactivity. The possibility is considered that the ligand may be an inhibitor of pineal origin."}
{"id": "PMID:211160", "title": "Microneutralization tests for serological typing and subtyping of foot-and-mouth disease virus strains.", "content": "A microneutralization test for serotyping of FMD viruses is described. It is based on earlier observations by Booth, Rweyemamu & Pay (1978) that dose-response relationships in quantal microneutralizations often deviated from linearity. The typing test described therefore utilizes undiluted virus preparations. In about 90% of samples a positive typing was obtained in contrast with about 50% for the complement fixation test. The test was also found to be susceptible to minimal quantities of heterotypic viral contamination. For strain differentiation the microneutralization test was carried out as a checkerboard test. When compared with the complement fixation test it was found to be more specific. The necessity to utilize virus-neutralization test systems for comparing FMD virus strains particularly for the purpose of vaccine selection is emphasized. The two dimensional microneutralization test has been applied to a study of comparing FMDV vaccine strains for Europe, South America, the Middle East and East Africa.", "contents": "Microneutralization tests for serological typing and subtyping of foot-and-mouth disease virus strains. A microneutralization test for serotyping of FMD viruses is described. It is based on earlier observations by Booth, Rweyemamu & Pay (1978) that dose-response relationships in quantal microneutralizations often deviated from linearity. The typing test described therefore utilizes undiluted virus preparations. In about 90% of samples a positive typing was obtained in contrast with about 50% for the complement fixation test. The test was also found to be susceptible to minimal quantities of heterotypic viral contamination. For strain differentiation the microneutralization test was carried out as a checkerboard test. When compared with the complement fixation test it was found to be more specific. The necessity to utilize virus-neutralization test systems for comparing FMD virus strains particularly for the purpose of vaccine selection is emphasized. The two dimensional microneutralization test has been applied to a study of comparing FMDV vaccine strains for Europe, South America, the Middle East and East Africa."}
{"id": "PMID:211161", "title": "Conversion of Bordetella pertussis to Bordetella parapertussis.", "content": "The epidemiological and drug susceptibility data on whooping cough suggested a possibility that Bordetella pertussis converts in some way to Bordetella parapertussis. To prove this, B. pertussis strain 75 was treated with N-methyl-N'-nitro-N-nitrosoguanidine and a mutant resistant to staphcillin v and eight mutants resistant to trimethoprim were isolated. The staphcillin V-resistant mutant of B. pertussis agreed with all of the criteria of B. parapertussis and the trimethoprim-resistant mutants also agreed with many of these criteria. Thus, a hypothesis is presented that B. parapertussis is a mutant of B. pertussis which appeared in nature probably by a selective pressure of antibiotics.", "contents": "Conversion of Bordetella pertussis to Bordetella parapertussis. The epidemiological and drug susceptibility data on whooping cough suggested a possibility that Bordetella pertussis converts in some way to Bordetella parapertussis. To prove this, B. pertussis strain 75 was treated with N-methyl-N'-nitro-N-nitrosoguanidine and a mutant resistant to staphcillin v and eight mutants resistant to trimethoprim were isolated. The staphcillin V-resistant mutant of B. pertussis agreed with all of the criteria of B. parapertussis and the trimethoprim-resistant mutants also agreed with many of these criteria. Thus, a hypothesis is presented that B. parapertussis is a mutant of B. pertussis which appeared in nature probably by a selective pressure of antibiotics."}
{"id": "PMID:211162", "title": "Serum antibody to poliovirus in patients in a mental deficiency hospital, with particular reference to Down's syndrome.", "content": "Neutralization tests for poliovirus antibodies were carried out on 74 patients in an adult mental deficiency hospital: 37 patients with Down's syndrome and 37 non-Down's mental defectives. The distribution of antibody titres to poliovirus types 1, 2 and 3 did not differ significantly between the two groups. Most patients had antibody to at least one poliovirus type but less than a third had antibodies at a titre of 1/8 or greater to all three types. The low level of poliovirus immunity in this population may be of epidemiological importance.", "contents": "Serum antibody to poliovirus in patients in a mental deficiency hospital, with particular reference to Down's syndrome. Neutralization tests for poliovirus antibodies were carried out on 74 patients in an adult mental deficiency hospital: 37 patients with Down's syndrome and 37 non-Down's mental defectives. The distribution of antibody titres to poliovirus types 1, 2 and 3 did not differ significantly between the two groups. Most patients had antibody to at least one poliovirus type but less than a third had antibodies at a titre of 1/8 or greater to all three types. The low level of poliovirus immunity in this population may be of epidemiological importance."}
{"id": "PMID:211163", "title": "Detection of airborne polyoma virus.", "content": "Polyoma virus was recovered from the air of an animal laboratory housing mice infected with the virus. Air samples were obtained by means of a high volume air sampler and further concentrated by high speed centrifugation. Total concentration of the air samples was 7.5 x 10(7). Assay for polyoma virus was by mouse antibody production tests. Airborne polyoma virus was detected in four of six samples.", "contents": "Detection of airborne polyoma virus. Polyoma virus was recovered from the air of an animal laboratory housing mice infected with the virus. Air samples were obtained by means of a high volume air sampler and further concentrated by high speed centrifugation. Total concentration of the air samples was 7.5 x 10(7). Assay for polyoma virus was by mouse antibody production tests. Airborne polyoma virus was detected in four of six samples."}
{"id": "PMID:211164", "title": "Sodium polyanethole sulfonate: a new macrophage-dependent polymyxin-inhibitable, polyclonal B cell activator.", "content": "The anionic detergent sodium polyanethole sulfonate was found to activate mouse B lymphocytes to increased cell division and formation of plaque-forming cells, possibly by an indirect mechanism. An increased cell division was also obtained in guinea pig and in rabbit lymphooid cell cultures. A strong similarity was found when comparing the dextran sulfate- and the sodium polyanethole sulfonate-sensitive cell population. Thus, the responding mouse cells resided in spleen and lymph node and also in fetal liver and bone marrow. The sensitive lymphocytes were dependent on the presence of macrophages or macrophage-replacing factors, since depletion of phagocytic cells resulted in loss of response. Addition of polymyxin B inhibited the stimulation, possibly through a direct interaction with the polyanion. In potency sodium polyanethole sulfonate was found to surpass dextran sulfate, making this benzene sulfonate a useful tool when studying lymphocyte responses.", "contents": "Sodium polyanethole sulfonate: a new macrophage-dependent polymyxin-inhibitable, polyclonal B cell activator. The anionic detergent sodium polyanethole sulfonate was found to activate mouse B lymphocytes to increased cell division and formation of plaque-forming cells, possibly by an indirect mechanism. An increased cell division was also obtained in guinea pig and in rabbit lymphooid cell cultures. A strong similarity was found when comparing the dextran sulfate- and the sodium polyanethole sulfonate-sensitive cell population. Thus, the responding mouse cells resided in spleen and lymph node and also in fetal liver and bone marrow. The sensitive lymphocytes were dependent on the presence of macrophages or macrophage-replacing factors, since depletion of phagocytic cells resulted in loss of response. Addition of polymyxin B inhibited the stimulation, possibly through a direct interaction with the polyanion. In potency sodium polyanethole sulfonate was found to surpass dextran sulfate, making this benzene sulfonate a useful tool when studying lymphocyte responses."}
{"id": "PMID:211165", "title": "Intracellular control of human neutrophil secretion. I. C5a-induced stimulus-specific desensitization and the effects of cytochalasin B.", "content": "Human neutrophils released the granule constituents myeloperoxidase and lysozyme, but not the cytoplasmic enzyme lactic dehydrogenase, when pretreated with cytochalasin B and stimulated with purified human C5a. Prior exposure to C5a before the cytochalasin B, however, abrogated the subsequent secretory process. Interaction of neutrophils with C5a was shown to result in a concentration-dependent rapid desensitization that could not be overcome by later addition of cytochalasin B or of cytochalasin B and C5a. The effect was relatively stimulus specific in that neutrophils desensitized in this manner could be induced to release granule enzymes by casein or by complement-coated zymosan particles. Cytochalasin B effects on neutrophils appear to mimic those of surface binding of soluble stimuli such as C5a and immune complexes. It is suggested that desensitization in concert with surface stimulation may represent an important intracellular mechanism for limiting neutrophil secretion.", "contents": "Intracellular control of human neutrophil secretion. I. C5a-induced stimulus-specific desensitization and the effects of cytochalasin B. Human neutrophils released the granule constituents myeloperoxidase and lysozyme, but not the cytoplasmic enzyme lactic dehydrogenase, when pretreated with cytochalasin B and stimulated with purified human C5a. Prior exposure to C5a before the cytochalasin B, however, abrogated the subsequent secretory process. Interaction of neutrophils with C5a was shown to result in a concentration-dependent rapid desensitization that could not be overcome by later addition of cytochalasin B or of cytochalasin B and C5a. The effect was relatively stimulus specific in that neutrophils desensitized in this manner could be induced to release granule enzymes by casein or by complement-coated zymosan particles. Cytochalasin B effects on neutrophils appear to mimic those of surface binding of soluble stimuli such as C5a and immune complexes. It is suggested that desensitization in concert with surface stimulation may represent an important intracellular mechanism for limiting neutrophil secretion."}
{"id": "PMID:211166", "title": "Potentiation of lymphocyte activation by colchicine.", "content": "Proliferation of human lymphocytes induced by IO4- is potentiated by 30 min exposure to colchicine (10(-6)M), whereas the response to Con A is inhibited. Treatment with colchicine before or after IO4- modification has similar enhancing effects. Lumicolchicine does not alter proliferative responses. In addition to the proliferation of IO4--oxidized cells, irradiated IO4- modified lymphocytes induce proliferation when mixed with untreated lymphocytes. Enhancement occurs in both these conditions only when IO4--modified cells are treated with colchicine. Preliminary data indicate that proliferation in mixed lymphocyte cultures is also potentiated when either stimulating or responding cells are pretreated with colchicine. These findings suggest a selective stimulatory effect of colchicine on lymphocyte responses induced by cell-cell contact. Agents that modify microtubular assemblies might regulate the induction of immune responses that involve cellular interactions.", "contents": "Potentiation of lymphocyte activation by colchicine. Proliferation of human lymphocytes induced by IO4- is potentiated by 30 min exposure to colchicine (10(-6)M), whereas the response to Con A is inhibited. Treatment with colchicine before or after IO4- modification has similar enhancing effects. Lumicolchicine does not alter proliferative responses. In addition to the proliferation of IO4--oxidized cells, irradiated IO4- modified lymphocytes induce proliferation when mixed with untreated lymphocytes. Enhancement occurs in both these conditions only when IO4--modified cells are treated with colchicine. Preliminary data indicate that proliferation in mixed lymphocyte cultures is also potentiated when either stimulating or responding cells are pretreated with colchicine. These findings suggest a selective stimulatory effect of colchicine on lymphocyte responses induced by cell-cell contact. Agents that modify microtubular assemblies might regulate the induction of immune responses that involve cellular interactions."}
{"id": "PMID:211169", "title": "Enhanced chemotactic and phagocytic activities of leukocytes in psoriasis vulgaris.", "content": "Leukocytes derived from the peripheral blood of psoriatic patients demonstrated an enhanced chemotactic response compared with leukocytes from healthy subjects. No significant difference was detected between the chemotactic response of leukocytes from patients with minimal or no skin involvement and those from patients with extensive lesions. Psoriatic leukocytes also had a significantly higher capacity to engulf 125I labeled Shigella flexneri than control leukocytes. It is postulated that a decrease in the cyclic AMP/cyclic GMP ratio in psoriatic leukocytes, similar to the imbalance of these 2 cyclic nucleotides found in the lesional epidermis of psoriasis, might be the cause of their enhanced chemotactic and phagocytic activities.", "contents": "Enhanced chemotactic and phagocytic activities of leukocytes in psoriasis vulgaris. Leukocytes derived from the peripheral blood of psoriatic patients demonstrated an enhanced chemotactic response compared with leukocytes from healthy subjects. No significant difference was detected between the chemotactic response of leukocytes from patients with minimal or no skin involvement and those from patients with extensive lesions. Psoriatic leukocytes also had a significantly higher capacity to engulf 125I labeled Shigella flexneri than control leukocytes. It is postulated that a decrease in the cyclic AMP/cyclic GMP ratio in psoriatic leukocytes, similar to the imbalance of these 2 cyclic nucleotides found in the lesional epidermis of psoriasis, might be the cause of their enhanced chemotactic and phagocytic activities."}
{"id": "PMID:211171", "title": "Effects of ascorbic acid deficiency on adrenal mitochondrial hydroxylations in guinea pigs.", "content": "The effect of ascorbic acid deficiency on adrenal hydroxylation of cholesterol and deoxycorticosterone in guinea pigs was studied by using mitochondria and isolated cytochrome P-450 fractions. The effects obtained were compared with the effects of long-term treatment with ACTH. Advanced scurvy as well as treatment with ACTH resulted in an increase in the weight of the adrenals, the total amount of cytochrome P-450, the cholesterol side-chain cleavage activity, the cortisol level in plasma, and the excretion of unconjugated cortisol in urine. Total 11beta- and 18-hydroxylation of deoxycorticosterone were not stimulated or were stimulated only to a small extent. It is suggested that the major effects observed in advanced scurvy are due to ACTH, the level of which was significantly increased, most probably as a consequence of the stress. In animals kept on a scorbutogenic diet for 2-4 weeks or, with a small dose of ascorbate added, for several weeks, changes were observed that could not be fully explained as effects of ACTH on normal adrenals. Although the plasma levels of ACTH and cortisol were increased only to a small extent and excretion of unconjugated cortisol in urine was unaffected, there was a significant increase in the total capacity of adrenal mitochondria to hydroxylate exogenous cholesterol. It is concluded that the level of ascorbate in the adrenals might be of some importance for the capacity to convert cholesterol into pregnenolone. The normal feed-back regulation is, however, intact in moderate ascorbate deficiency and the plasma level of cortisol is kept within normal limits.", "contents": "Effects of ascorbic acid deficiency on adrenal mitochondrial hydroxylations in guinea pigs. The effect of ascorbic acid deficiency on adrenal hydroxylation of cholesterol and deoxycorticosterone in guinea pigs was studied by using mitochondria and isolated cytochrome P-450 fractions. The effects obtained were compared with the effects of long-term treatment with ACTH. Advanced scurvy as well as treatment with ACTH resulted in an increase in the weight of the adrenals, the total amount of cytochrome P-450, the cholesterol side-chain cleavage activity, the cortisol level in plasma, and the excretion of unconjugated cortisol in urine. Total 11beta- and 18-hydroxylation of deoxycorticosterone were not stimulated or were stimulated only to a small extent. It is suggested that the major effects observed in advanced scurvy are due to ACTH, the level of which was significantly increased, most probably as a consequence of the stress. In animals kept on a scorbutogenic diet for 2-4 weeks or, with a small dose of ascorbate added, for several weeks, changes were observed that could not be fully explained as effects of ACTH on normal adrenals. Although the plasma levels of ACTH and cortisol were increased only to a small extent and excretion of unconjugated cortisol in urine was unaffected, there was a significant increase in the total capacity of adrenal mitochondria to hydroxylate exogenous cholesterol. It is concluded that the level of ascorbate in the adrenals might be of some importance for the capacity to convert cholesterol into pregnenolone. The normal feed-back regulation is, however, intact in moderate ascorbate deficiency and the plasma level of cortisol is kept within normal limits."}
{"id": "PMID:211172", "title": "Cyclic AMP metabolism in adipose tissue of exercise-trained rats.", "content": "Cyclic AMP metabolism in epididymal adipose tissue of exercise-trained rats was examined to determine if training induced changes in cyclic AMP production or inactivation. Beginning at 7 weeks of age, male rats were physically trained by 12 weeks of treadmill running. Pair-fed control rats remained sedentary in their cages for the duration of the experiment. Tissue levels of cyclic AMP were measured in epididymal adipose tissue slices incubated with norepinephrine. Adenyl cyclase was assayed in adipocyte ghost cell prepartions and low-Km phosphodiesterase was assayed in homogenates of adipose tissue. In response to norepinephrine stimulation, tissue cyclic AMP levels were reduced in trained compared to untrained rats. Training increased the ratio of activity of phosphodiesterase relative to adenyl cyclase. The results of this study indicate that cyclic AMP production in response to norepinephrine stimulation is not increased by training and may even be reduced, implying that adipose tissue cyclic AMP levels may be under a greater degree of control in trained rats. Modulation of adipose tissue cyclic AMP levels may function to regulate more closely the duration of lipolysis in exercise-trained rats.", "contents": "Cyclic AMP metabolism in adipose tissue of exercise-trained rats. Cyclic AMP metabolism in epididymal adipose tissue of exercise-trained rats was examined to determine if training induced changes in cyclic AMP production or inactivation. Beginning at 7 weeks of age, male rats were physically trained by 12 weeks of treadmill running. Pair-fed control rats remained sedentary in their cages for the duration of the experiment. Tissue levels of cyclic AMP were measured in epididymal adipose tissue slices incubated with norepinephrine. Adenyl cyclase was assayed in adipocyte ghost cell prepartions and low-Km phosphodiesterase was assayed in homogenates of adipose tissue. In response to norepinephrine stimulation, tissue cyclic AMP levels were reduced in trained compared to untrained rats. Training increased the ratio of activity of phosphodiesterase relative to adenyl cyclase. The results of this study indicate that cyclic AMP production in response to norepinephrine stimulation is not increased by training and may even be reduced, implying that adipose tissue cyclic AMP levels may be under a greater degree of control in trained rats. Modulation of adipose tissue cyclic AMP levels may function to regulate more closely the duration of lipolysis in exercise-trained rats."}
{"id": "PMID:211173", "title": "Cyclic AMP-sensitive activation of hepatic sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase.", "content": "We previously showed that preincubation of a 10,000 g supernatant (S(10)) from rat liver for 20 min at 37 degrees C dramatically increased the subsequent incorporation of [(14)C]acetate into sterols. No activation was seen with [(14)C]mevalonate as substrate. In the present studies we have examined the effect of preincubation on HMG CoA reductase. When microsomes were isolated from S(10) by calcium precipitation, preincubation of S(10) increased the specific activity of HMG CoA reductase threefold. No activation of HMG CoA reductase was observed in microsomes isolated by ultracentrifugation. Activation was cyclic AMP-sensitive. When cyclic AMP (0.001-1.0 mM) and MgATP (1 mM) were present during the preincubation period, there was little or no activation of HMG CoA reductase activity or of sterol synthesis from acetate. MgATP alone did not prevent activation. Neither cyclic AMP nor MgATP was inhibitory when present only during the assay of sterol synthesis. We propose that the in vitro activation represents the reversal of a physiologic cyclic AMP-mediated mechanism for the control of hepatic HMG CoA reductase. That a phosphoprotein phosphatase may catalyze the activation was supported by the observation that sodium fluoride, an inhibitor of phosphoprotein phosphatases, inhibited the activation. These results suggest that hormone-induced changes in the cellular level of cyclic AMP may regulate the activity of HMG CoA reductase and the rate of hepatic cholesterol synthesis.", "contents": "Cyclic AMP-sensitive activation of hepatic sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase. We previously showed that preincubation of a 10,000 g supernatant (S(10)) from rat liver for 20 min at 37 degrees C dramatically increased the subsequent incorporation of [(14)C]acetate into sterols. No activation was seen with [(14)C]mevalonate as substrate. In the present studies we have examined the effect of preincubation on HMG CoA reductase. When microsomes were isolated from S(10) by calcium precipitation, preincubation of S(10) increased the specific activity of HMG CoA reductase threefold. No activation of HMG CoA reductase was observed in microsomes isolated by ultracentrifugation. Activation was cyclic AMP-sensitive. When cyclic AMP (0.001-1.0 mM) and MgATP (1 mM) were present during the preincubation period, there was little or no activation of HMG CoA reductase activity or of sterol synthesis from acetate. MgATP alone did not prevent activation. Neither cyclic AMP nor MgATP was inhibitory when present only during the assay of sterol synthesis. We propose that the in vitro activation represents the reversal of a physiologic cyclic AMP-mediated mechanism for the control of hepatic HMG CoA reductase. That a phosphoprotein phosphatase may catalyze the activation was supported by the observation that sodium fluoride, an inhibitor of phosphoprotein phosphatases, inhibited the activation. These results suggest that hormone-induced changes in the cellular level of cyclic AMP may regulate the activity of HMG CoA reductase and the rate of hepatic cholesterol synthesis."}
{"id": "PMID:211176", "title": "An improved and simple micro-method of sphingomyelinase assay in leukocytes and urine.", "content": "A simple one-vial-method was developed for the quantitative determination of sphingomyelinase activity in human leukocytes and urine, using [14C-methyl] sphingomyelin. The measured activities of healthy control persons show a higher scatter in (n=50) urine (1.2 +/- 0.5 nmol/h . ml urine) than in (n=9) leukocytes (2.15 +/- 0.35 nmol/h . mg protein). Long term tests showed that the enzyme activities in urine can best be correlated to the 24-h-creatinine excretion. A distinct loss of enzyme activity was found in dialyzed urine starting at about the third day; this did not occur in undialyzed urine. The method also shows good reproducibility in micro-tests. It is therefore suitable for screening tests (urine of persons suffering from Niemann Pick disease) and for the prenatal diagnosis of sphingomyelinosis. For one out of two children with symptoms of sphingomyelinosis (hepatosplenomegaly, mental retardation, and neurological deterioration) the diagnosis was confirmed by morphological examination of tissues obtained by biopsy. In both cases leukocytes and urine revealed normal sphingomyelinase activity. These biochemical results in conjunction with the clinical and morphological picture were indicative of type C Niemann-Pick disease.", "contents": "An improved and simple micro-method of sphingomyelinase assay in leukocytes and urine. A simple one-vial-method was developed for the quantitative determination of sphingomyelinase activity in human leukocytes and urine, using [14C-methyl] sphingomyelin. The measured activities of healthy control persons show a higher scatter in (n=50) urine (1.2 +/- 0.5 nmol/h . ml urine) than in (n=9) leukocytes (2.15 +/- 0.35 nmol/h . mg protein). Long term tests showed that the enzyme activities in urine can best be correlated to the 24-h-creatinine excretion. A distinct loss of enzyme activity was found in dialyzed urine starting at about the third day; this did not occur in undialyzed urine. The method also shows good reproducibility in micro-tests. It is therefore suitable for screening tests (urine of persons suffering from Niemann Pick disease) and for the prenatal diagnosis of sphingomyelinosis. For one out of two children with symptoms of sphingomyelinosis (hepatosplenomegaly, mental retardation, and neurological deterioration) the diagnosis was confirmed by morphological examination of tissues obtained by biopsy. In both cases leukocytes and urine revealed normal sphingomyelinase activity. These biochemical results in conjunction with the clinical and morphological picture were indicative of type C Niemann-Pick disease."}
{"id": "PMID:211177", "title": "The spatiotemporal transfer function of the Limulus lateral eye.", "content": "The dynamics of the Limulus retina may be well described by the spatiotemporal transfer function, which measures the response of the eye to moving sinusoidal gratings. We consider a model for this system, which incorporates an excitatory generator potential, and self- and lateral inhibitory processes. Procedures are described which allow estimation of parameters for the model consistent with the empirical transfer function data. Transfer functions calculated from the model show good agreement with laboratory measurements, and may be used to predict accurately the response of the eye to arbitrary moving stimuli. The model allows convenient interpretation of the transfer function measurements in terms of physiological processes which underly the response of the Limulus retina.", "contents": "The spatiotemporal transfer function of the Limulus lateral eye. The dynamics of the Limulus retina may be well described by the spatiotemporal transfer function, which measures the response of the eye to moving sinusoidal gratings. We consider a model for this system, which incorporates an excitatory generator potential, and self- and lateral inhibitory processes. Procedures are described which allow estimation of parameters for the model consistent with the empirical transfer function data. Transfer functions calculated from the model show good agreement with laboratory measurements, and may be used to predict accurately the response of the eye to arbitrary moving stimuli. The model allows convenient interpretation of the transfer function measurements in terms of physiological processes which underly the response of the Limulus retina."}
{"id": "PMID:211178", "title": "The fine structure of cells infected with temperature-sensitive mutants of herpes simplex virus type 2.", "content": "The fine structure of cells infected with the HG 52 strain of herpes simplex virus type 2 and 13 temperature-sensitive mutants derived from it was investigated. In cells infected with the wild-type virus, development of virions appeared to be similar to that described in previous reports. However there were two exceptions to this: (1) capsid envelopment apparently occurred de novo in the nucleus; (2) densely staining vacuolar accumulations were seen, frequently surrounding virus capsids. The 13 temperature-sensitive mutants of the virus were divided into three classes according to the type of capsid, if any, produced in cells infected and maintained at the non-permissive temperature. Class I mutants produced no capsids, Class II mutants produced empty and partial-cored capsids and Class III mutants produced empty, partial- and dense-cored capsids. Cellular alterations were also determined. Membranous tubular structures, previously unreported for herpes simplex virus, were observed in cells infected with Class III mutants and very occasionally with wild-type virus at the non-permissive temperature. Cytoplasmic particles were also found, but could not be correlated with any particular class of mutant.", "contents": "The fine structure of cells infected with temperature-sensitive mutants of herpes simplex virus type 2. The fine structure of cells infected with the HG 52 strain of herpes simplex virus type 2 and 13 temperature-sensitive mutants derived from it was investigated. In cells infected with the wild-type virus, development of virions appeared to be similar to that described in previous reports. However there were two exceptions to this: (1) capsid envelopment apparently occurred de novo in the nucleus; (2) densely staining vacuolar accumulations were seen, frequently surrounding virus capsids. The 13 temperature-sensitive mutants of the virus were divided into three classes according to the type of capsid, if any, produced in cells infected and maintained at the non-permissive temperature. Class I mutants produced no capsids, Class II mutants produced empty and partial-cored capsids and Class III mutants produced empty, partial- and dense-cored capsids. Cellular alterations were also determined. Membranous tubular structures, previously unreported for herpes simplex virus, were observed in cells infected with Class III mutants and very occasionally with wild-type virus at the non-permissive temperature. Cytoplasmic particles were also found, but could not be correlated with any particular class of mutant."}
{"id": "PMID:211179", "title": "Simultaneous production of mouse endogenous virus and Rous sarcoma virus by Schmidt-Ruppin virus infected mouse cells.", "content": "Schmidt-Ruppin Rous sarcoma virus infected chick cells injected into newborn C3H/f mice gave rise to tumours at the site of inoculation. These tumours were transplantable in adult C3H/f mice and were able to induce tumours in the wing of adult Leghorn chickens. Tumour cells from the 18th passage in mice were used to establish a cell line in tissue culture (C3HSR). These cells released C-type virus particles that produced foci and were able to propagate in chick cells. Cloning of the C3HSR cells demonstrated that the same cell expressed both avian and murine antigens. Mouse cells infected with virus released by C3HSR cells produced murine leukaemia virus-like particles as revealed by the reverse XC syncytial test and by immunofluorescence tests.", "contents": "Simultaneous production of mouse endogenous virus and Rous sarcoma virus by Schmidt-Ruppin virus infected mouse cells. Schmidt-Ruppin Rous sarcoma virus infected chick cells injected into newborn C3H/f mice gave rise to tumours at the site of inoculation. These tumours were transplantable in adult C3H/f mice and were able to induce tumours in the wing of adult Leghorn chickens. Tumour cells from the 18th passage in mice were used to establish a cell line in tissue culture (C3HSR). These cells released C-type virus particles that produced foci and were able to propagate in chick cells. Cloning of the C3HSR cells demonstrated that the same cell expressed both avian and murine antigens. Mouse cells infected with virus released by C3HSR cells produced murine leukaemia virus-like particles as revealed by the reverse XC syncytial test and by immunofluorescence tests."}
{"id": "PMID:211180", "title": "The effect of trypsin on the growth of rotavirus.", "content": "It has been found that 1000-fold more bovine rotavirus is obtained when trypsin is incorporated in the maintenance medium and allowed to remain throughout the growth cycle. This holds true for primary calf kidney (CK) cells and also for several continuous and semi-continuous cell lines. In the presence of trypsin it has been possible to pass the virus serially on continuous cell lines seven times. Concentrations of 1 to 10 microgram/ml of trypsin are found to be effective. Preliminary results suggest that the same technique will be effective for the in vitro propagation of human rotavirus.", "contents": "The effect of trypsin on the growth of rotavirus. It has been found that 1000-fold more bovine rotavirus is obtained when trypsin is incorporated in the maintenance medium and allowed to remain throughout the growth cycle. This holds true for primary calf kidney (CK) cells and also for several continuous and semi-continuous cell lines. In the presence of trypsin it has been possible to pass the virus serially on continuous cell lines seven times. Concentrations of 1 to 10 microgram/ml of trypsin are found to be effective. Preliminary results suggest that the same technique will be effective for the in vitro propagation of human rotavirus."}
{"id": "PMID:211181", "title": "The use of guanidine-HCl for the isolation of both RNA and protein from RNA tumour viruses.", "content": "The RNA components of two C-type RNA viruses, avian myeloblastosis virus and Friend leukaemia virus, have been isolated by treatment of the viruses with 6 M-guanidine-HCl and precipitation with ethanol. The virus proteins were recovered by lyophilization of the guanidine-HCl-ethanol supernatant after thorough dialysis against 0.5 mM-dithiothreitol. This simple method yielded RNA of similar quality to the phenol and sodium dodecyl sulphate (SDS) extraction methods, and the same amount of 60-70S RNA, although a fraction of the smaller (4S) species remained in the protein fraction. The sedimentation patterns of heat-denatured RNA extracted by either method were similar. Electrophoretic analyses of the extracted proteins in polyacrylamide gel gradients containing SDS gave patterns that were very similar to those obtained by direct analysis of SDS disrupted viruses.", "contents": "The use of guanidine-HCl for the isolation of both RNA and protein from RNA tumour viruses. The RNA components of two C-type RNA viruses, avian myeloblastosis virus and Friend leukaemia virus, have been isolated by treatment of the viruses with 6 M-guanidine-HCl and precipitation with ethanol. The virus proteins were recovered by lyophilization of the guanidine-HCl-ethanol supernatant after thorough dialysis against 0.5 mM-dithiothreitol. This simple method yielded RNA of similar quality to the phenol and sodium dodecyl sulphate (SDS) extraction methods, and the same amount of 60-70S RNA, although a fraction of the smaller (4S) species remained in the protein fraction. The sedimentation patterns of heat-denatured RNA extracted by either method were similar. Electrophoretic analyses of the extracted proteins in polyacrylamide gel gradients containing SDS gave patterns that were very similar to those obtained by direct analysis of SDS disrupted viruses."}
{"id": "PMID:211182", "title": "Infection of mouse liver by human adenovirus type 5.", "content": "CBA mice, inoculated intravenously with large doses of adenovirus type 5, showed raised levels of serum aspartate aminotransferase (SAAT; EC 2.6.I.I) and died within a few days from histologically demonstrable hepatic necrosis. After inoculation of I LD50, virus was rapidly taken up by the tissues where infectivity then declined greatly. Organ titres then increased about 100-fold by 48 h p.i. but, in the liver, which showed intranuclear inclusion bodies, and by electron microscopy, scattered intranuclear and intracytoplasmic adenovirions, the increase was 10000- to 100000-fold. P antigen was detected by single radial diffusion in liver extracts, and by immunofluorescence in 80% of liver cells at 36 h p.i. Hexon, penton base and fibre antigens appeared later and in fewer cells. The maximum amount of hexon, of demonstrable type 5 specificity, was shown by radioimmunoassay to be equivalent to up to 5 x 1011 whole adenovirions/g liver. It is concluded that human adenovirus type 5 undergoes an abortive but lytic infection in most liver cells but that replication may proceed to completion in a few.", "contents": "Infection of mouse liver by human adenovirus type 5. CBA mice, inoculated intravenously with large doses of adenovirus type 5, showed raised levels of serum aspartate aminotransferase (SAAT; EC 2.6.I.I) and died within a few days from histologically demonstrable hepatic necrosis. After inoculation of I LD50, virus was rapidly taken up by the tissues where infectivity then declined greatly. Organ titres then increased about 100-fold by 48 h p.i. but, in the liver, which showed intranuclear inclusion bodies, and by electron microscopy, scattered intranuclear and intracytoplasmic adenovirions, the increase was 10000- to 100000-fold. P antigen was detected by single radial diffusion in liver extracts, and by immunofluorescence in 80% of liver cells at 36 h p.i. Hexon, penton base and fibre antigens appeared later and in fewer cells. The maximum amount of hexon, of demonstrable type 5 specificity, was shown by radioimmunoassay to be equivalent to up to 5 x 1011 whole adenovirions/g liver. It is concluded that human adenovirus type 5 undergoes an abortive but lytic infection in most liver cells but that replication may proceed to completion in a few."}
{"id": "PMID:211183", "title": "Defective herpes simplex virus DNA: circular and circular-linear molecules resembling rolling circles.", "content": "The formation of defective herpes simplex virus (HSV) in BSC-1 cells and the synthesis of defective virus DNA was studied. The fourth consecutive passage of undiluted virus yielded defective DNA that was 0.008 g/ml more dense than wild type (w.t.) virus DNA. The amount of defective DNA increased at passage 6 concomitantly with the decrease in infectious virus progeny. The synthesis of defective DNA was always accompanied by w.t. virus DNA synthesis. Defective DNA from both infected nuclei and defective virions had a mol. wt. of 100 X 10(6) and was linear as determined by electron microscopy. Electron microscopy of defective virus DNA at passage 6 revealed circular molecules varying in size in addition to linear DNA molecules with the length of intact virion DNA. The circular DNA molecules had contour lengths of 10, 5, 2.5 and less than 2.5 micron. The smallest circular DNA molecules had a contour length of 0.3 micron, possibly one virus gene. In addition, circular-linear DNA molecules were observed in which both the circular and the linear components varied in length. Most of these DNA molecules had circular components of either 2.5 or 5.0 micron, and linear components varying in length from less than 1 to 50 micron. Based on the present study, it is proposed that the S component of w.t. virus DNA is fragmented into small circular molecules that serve as templates for DNA synthesis, possibly by the rolling circle mechanism.", "contents": "Defective herpes simplex virus DNA: circular and circular-linear molecules resembling rolling circles. The formation of defective herpes simplex virus (HSV) in BSC-1 cells and the synthesis of defective virus DNA was studied. The fourth consecutive passage of undiluted virus yielded defective DNA that was 0.008 g/ml more dense than wild type (w.t.) virus DNA. The amount of defective DNA increased at passage 6 concomitantly with the decrease in infectious virus progeny. The synthesis of defective DNA was always accompanied by w.t. virus DNA synthesis. Defective DNA from both infected nuclei and defective virions had a mol. wt. of 100 X 10(6) and was linear as determined by electron microscopy. Electron microscopy of defective virus DNA at passage 6 revealed circular molecules varying in size in addition to linear DNA molecules with the length of intact virion DNA. The circular DNA molecules had contour lengths of 10, 5, 2.5 and less than 2.5 micron. The smallest circular DNA molecules had a contour length of 0.3 micron, possibly one virus gene. In addition, circular-linear DNA molecules were observed in which both the circular and the linear components varied in length. Most of these DNA molecules had circular components of either 2.5 or 5.0 micron, and linear components varying in length from less than 1 to 50 micron. Based on the present study, it is proposed that the S component of w.t. virus DNA is fragmented into small circular molecules that serve as templates for DNA synthesis, possibly by the rolling circle mechanism."}
{"id": "PMID:211184", "title": "Photochemical inactivation of DNA and RNA viruses by psoralen derivatives.", "content": "Western equine encephalitis virus, and RNA virus, and herpes simplex virus type I, a DNA virus, were efficiently inactivated in less than I min by exposure to long-wave ultraviolet light (320 to 380 nm) in the presence of several psoralen derivatives. The psoralen photochemical reaction was chosen for study due to its known specificity for nucleic acids. Neither the light nor any of the drugs alone caused appreciable inactivation. The inactivation kinetics and dependence on light intensity and on different derivatives of psoralen were studied. The high solubility of a new aminomethyl psoralen derivative was found to be advantageous in the photochemical inactivation of the RNA virus, but was not in the case of the more easily inactivated DNA virus. Within its limited solubility range trimethylpsoralen was superior to its aminomethyl derivative on a molar basis for the inactivation of both types of viruses under most of the conditions studied.", "contents": "Photochemical inactivation of DNA and RNA viruses by psoralen derivatives. Western equine encephalitis virus, and RNA virus, and herpes simplex virus type I, a DNA virus, were efficiently inactivated in less than I min by exposure to long-wave ultraviolet light (320 to 380 nm) in the presence of several psoralen derivatives. The psoralen photochemical reaction was chosen for study due to its known specificity for nucleic acids. Neither the light nor any of the drugs alone caused appreciable inactivation. The inactivation kinetics and dependence on light intensity and on different derivatives of psoralen were studied. The high solubility of a new aminomethyl psoralen derivative was found to be advantageous in the photochemical inactivation of the RNA virus, but was not in the case of the more easily inactivated DNA virus. Within its limited solubility range trimethylpsoralen was superior to its aminomethyl derivative on a molar basis for the inactivation of both types of viruses under most of the conditions studied."}
{"id": "PMID:211185", "title": "Attachment of herpes simplex virus to neurons and glial cells.", "content": "Cells of brain tissue of rabbits, rats and mice were dissociated and glial cells, neuronal perikarya and synaptosomes were separated by centrifugation on discontinuous Ficol gradients. HSV was shown to attach well to rat and rabbit glial cells and synaptosomes but not to neuronal perikarya. Of intracerebrally infected mice the fractions with glial cells contained the infective virus. The interactions between HSV and neuronal cells and the implication of the observations on the HSV infection of the nervous system are discussed.", "contents": "Attachment of herpes simplex virus to neurons and glial cells. Cells of brain tissue of rabbits, rats and mice were dissociated and glial cells, neuronal perikarya and synaptosomes were separated by centrifugation on discontinuous Ficol gradients. HSV was shown to attach well to rat and rabbit glial cells and synaptosomes but not to neuronal perikarya. Of intracerebrally infected mice the fractions with glial cells contained the infective virus. The interactions between HSV and neuronal cells and the implication of the observations on the HSV infection of the nervous system are discussed."}
{"id": "PMID:211186", "title": "Potentiation of the neurtalization of feline leukaemia virus in hypotonic medium.", "content": "The neutralization of feline leukaemia virus could be enhanced by performing the reaction in hypotonic medium. Absorption of antibody by virus specific antigens was also made more sensitive under these conditions.", "contents": "Potentiation of the neurtalization of feline leukaemia virus in hypotonic medium. The neutralization of feline leukaemia virus could be enhanced by performing the reaction in hypotonic medium. Absorption of antibody by virus specific antigens was also made more sensitive under these conditions."}
{"id": "PMID:211187", "title": "Replication of herpesviruses in human cells transformed by cytomegalovirus.", "content": "The replication of human cytomegalovirus (CMV) and herpes simplex virus (HSV) was studied in three human embryo cell lines (CMV-Mj-HEL-I, CMV-Mj-HEL-2, and CMV-Mj-HEL-2,T-I) transformed in vitro by human CMV. Growth studies revealed that these cells were completely resistant to infection by CMV strains ADI69 and Mj and partially resistant to HSV types I and 2. Neither virus DNA nor virus proteins were synthesized in the transformed cells infected with CMV AD169. The HSV production in CMV-transformed human embryo lung (HEL) cells was delayed when compared to the virus production in normal HEL cells and spread of HSV c.p.e. was slower in the transformed cells. The treatment of normal HEL cells with a crude extract of CMV-transformed HEL cells also resulted in inhibition of the spread of c.p.e. of HSV types I and 2. The inhibitory effect was not due to interferon since vesicular stomatitis virus replication was not affected and several experiments showed that it was not due to mycoplasma. The presence of virus inhibitor molecules in CMV-transformed cells absent in normal HEL cells is postulated.", "contents": "Replication of herpesviruses in human cells transformed by cytomegalovirus. The replication of human cytomegalovirus (CMV) and herpes simplex virus (HSV) was studied in three human embryo cell lines (CMV-Mj-HEL-I, CMV-Mj-HEL-2, and CMV-Mj-HEL-2,T-I) transformed in vitro by human CMV. Growth studies revealed that these cells were completely resistant to infection by CMV strains ADI69 and Mj and partially resistant to HSV types I and 2. Neither virus DNA nor virus proteins were synthesized in the transformed cells infected with CMV AD169. The HSV production in CMV-transformed human embryo lung (HEL) cells was delayed when compared to the virus production in normal HEL cells and spread of HSV c.p.e. was slower in the transformed cells. The treatment of normal HEL cells with a crude extract of CMV-transformed HEL cells also resulted in inhibition of the spread of c.p.e. of HSV types I and 2. The inhibitory effect was not due to interferon since vesicular stomatitis virus replication was not affected and several experiments showed that it was not due to mycoplasma. The presence of virus inhibitor molecules in CMV-transformed cells absent in normal HEL cells is postulated."}
{"id": "PMID:211188", "title": "Sensitivity of the transforming and replicative functions of Epstein--Barr virus to inhibition by phosphonoacetate.", "content": "Disodium, phosphonoacetate (PA), at concentrations of 50 to 200 microgram/ml, which still allowed continued growth of the EB virus-transformed B95-8 cell line on a routine culture regimen, was able to inhibit the production of virus capsid antigen and of virus particles by these cells down to very low but finite levels which persisted despite prolonged treatment. Further experiments measured the effects of these same drug concentrations on the EB virus-induced in vitro transformation of foetal cord blood lymphocytes and on the colony forming ability of already established EB virus-transformed foetal cell lines; in both types of culture, doses of PA up to and including 50 microgram/ml did not affect cell growth within the 8-week observation period, whereas doses of 100 microgram/ml and above were increasingly inhibitory. The cell lines established by EB virus-induced transformation in the continual presence of PA at 50 to 150 microgram/ml contained multiple copies of the virus genome per cell just as did the corresponding cell lines established in control medium. The results argue against the existence of any PA-sensitive event unique to the EB virus-induced transformation process.", "contents": "Sensitivity of the transforming and replicative functions of Epstein--Barr virus to inhibition by phosphonoacetate. Disodium, phosphonoacetate (PA), at concentrations of 50 to 200 microgram/ml, which still allowed continued growth of the EB virus-transformed B95-8 cell line on a routine culture regimen, was able to inhibit the production of virus capsid antigen and of virus particles by these cells down to very low but finite levels which persisted despite prolonged treatment. Further experiments measured the effects of these same drug concentrations on the EB virus-induced in vitro transformation of foetal cord blood lymphocytes and on the colony forming ability of already established EB virus-transformed foetal cell lines; in both types of culture, doses of PA up to and including 50 microgram/ml did not affect cell growth within the 8-week observation period, whereas doses of 100 microgram/ml and above were increasingly inhibitory. The cell lines established by EB virus-induced transformation in the continual presence of PA at 50 to 150 microgram/ml contained multiple copies of the virus genome per cell just as did the corresponding cell lines established in control medium. The results argue against the existence of any PA-sensitive event unique to the EB virus-induced transformation process."}
{"id": "PMID:211189", "title": "Complement-mediated cytolysis of HSV-1 and HSV-2 infected cells: plasma membrane antigens reactive with type-specific and cross-reactive antibody.", "content": "Surface antigens of BHK-21 cells infected with HSV-1 or HSV-2 were radioiodinated (125I) with lactoperoxidase, immune precipitated and analysed by polyacrylamide gel electrophoresis (PAGE). Experiments using antiserum to HSV-1 or HSV-2, absorbed with appropriate hemotypic or heterotypic antigens, revealed that both type-specific (homotypic) and cross-reactive antibody combined with surface glycoproteins to form a single large radioactive peak. This peak, which constituted the major glycoprotein region (region a) observed in electropherograms, represented a range in mol. wt. from 115000 to 130000. Sensitization of cells to complement lysis, neutralization of infectious virus and immune precipitation of surface glycoproteins (region a) were found to be generally correlated properties of all the antibody preparations analysed, including antibody prepared specifically against region a antigens. These findings suggest a major immunological role for the surface glycoproteins migrating in PAGE region a.", "contents": "Complement-mediated cytolysis of HSV-1 and HSV-2 infected cells: plasma membrane antigens reactive with type-specific and cross-reactive antibody. Surface antigens of BHK-21 cells infected with HSV-1 or HSV-2 were radioiodinated (125I) with lactoperoxidase, immune precipitated and analysed by polyacrylamide gel electrophoresis (PAGE). Experiments using antiserum to HSV-1 or HSV-2, absorbed with appropriate hemotypic or heterotypic antigens, revealed that both type-specific (homotypic) and cross-reactive antibody combined with surface glycoproteins to form a single large radioactive peak. This peak, which constituted the major glycoprotein region (region a) observed in electropherograms, represented a range in mol. wt. from 115000 to 130000. Sensitization of cells to complement lysis, neutralization of infectious virus and immune precipitation of surface glycoproteins (region a) were found to be generally correlated properties of all the antibody preparations analysed, including antibody prepared specifically against region a antigens. These findings suggest a major immunological role for the surface glycoproteins migrating in PAGE region a."}
{"id": "PMID:211190", "title": "Improved detection of virus-specific IgM antibodies. Elimination of non-specific IgM binding.", "content": "A non-specific reaction between human IgM and cytoplasmic structures of virus infected cells can often be observed if MgM antibodies to virus antigens are detected by indirect immunofluorescence or by immuno enzyme assays. Formaldehyde selectively inactivates the cytoplasmic receptors for human IgM without affecting the virus structural proteins. Alternatively, receptor-free antigens can be obtained by isolation of nuclei from virus infected cells. Due to reduced background, a more specific and more sensitive detection of IgM antibodies to Epstein-Barr virus, cytomegalovirus or central European encephalitis virus is possible.", "contents": "Improved detection of virus-specific IgM antibodies. Elimination of non-specific IgM binding. A non-specific reaction between human IgM and cytoplasmic structures of virus infected cells can often be observed if MgM antibodies to virus antigens are detected by indirect immunofluorescence or by immuno enzyme assays. Formaldehyde selectively inactivates the cytoplasmic receptors for human IgM without affecting the virus structural proteins. Alternatively, receptor-free antigens can be obtained by isolation of nuclei from virus infected cells. Due to reduced background, a more specific and more sensitive detection of IgM antibodies to Epstein-Barr virus, cytomegalovirus or central European encephalitis virus is possible."}
{"id": "PMID:211191", "title": "Metabolism of myoinositol in avian and mammalian cells infected with naked and enveloped DNA and RNA viruses.", "content": "The uptake of 3H-inositol into the pool of free inositol and its incorporation into the lipid phosphatidylinositol have been studied in various avian and mammalian cells infected by different viruses. In all the virus-cell systems investigated, virus infection results in a drastically reduced amount of free 3H-inositol about 3 to 5 h post-infection, demonstrable in the infected cells as compared to the mock-infected controls. In contrast, the incorporation of 3H-inositol into lipid can be enhanced, reduced, or not influenced at all, depending on the virus-cell system under observation.", "contents": "Metabolism of myoinositol in avian and mammalian cells infected with naked and enveloped DNA and RNA viruses. The uptake of 3H-inositol into the pool of free inositol and its incorporation into the lipid phosphatidylinositol have been studied in various avian and mammalian cells infected by different viruses. In all the virus-cell systems investigated, virus infection results in a drastically reduced amount of free 3H-inositol about 3 to 5 h post-infection, demonstrable in the infected cells as compared to the mock-infected controls. In contrast, the incorporation of 3H-inositol into lipid can be enhanced, reduced, or not influenced at all, depending on the virus-cell system under observation."}
{"id": "PMID:211192", "title": "Development of early nuclear antigen in cytomegalovirus infected cells in the presence of RNA and protein synthesis inhibitors.", "content": "Human cytomegaloviruses (HCMV) induce nuclear antigens as early as I h after infection as detected by immunofluorescence. Early antigen development occurs in the presence of DNA, RNA, and protein synthesis inhibitors and is dependent on intact viral DNA in the inoculum.", "contents": "Development of early nuclear antigen in cytomegalovirus infected cells in the presence of RNA and protein synthesis inhibitors. Human cytomegaloviruses (HCMV) induce nuclear antigens as early as I h after infection as detected by immunofluorescence. Early antigen development occurs in the presence of DNA, RNA, and protein synthesis inhibitors and is dependent on intact viral DNA in the inoculum."}
{"id": "PMID:211193", "title": "Properties of the viruses selected during persistent infection of L cells with VSV.", "content": "Two virus clones, VSV-mp and VSV-sp, were isolated from L cells persistently infected with VSV (New Jersey serotype). Both clones were more temperature sensitive than the parent virus, VSV-o, and grew more slowly, gave smaller plaques, less c.p.e. and lower virus yields in L cells. Unlike the parent virus, both persistent viruses induced interferon production in L cells. Stable carrier cultures could be obtained from L cells infected with VSV-sp at low multiplicities without pretreatment with interferon. This may be related to the fact that VSV-sp is more sensitive to interferon than either VSV-mp or VSV-o.", "contents": "Properties of the viruses selected during persistent infection of L cells with VSV. Two virus clones, VSV-mp and VSV-sp, were isolated from L cells persistently infected with VSV (New Jersey serotype). Both clones were more temperature sensitive than the parent virus, VSV-o, and grew more slowly, gave smaller plaques, less c.p.e. and lower virus yields in L cells. Unlike the parent virus, both persistent viruses induced interferon production in L cells. Stable carrier cultures could be obtained from L cells infected with VSV-sp at low multiplicities without pretreatment with interferon. This may be related to the fact that VSV-sp is more sensitive to interferon than either VSV-mp or VSV-o."}
{"id": "PMID:211194", "title": "Studies of Epstein-Barr virus (EBV)-associated nuclear antigen: solubilization from Raji cell chromatin with 5 M-urea-2 M-nacl and fractionation on hydroxyapatite.", "content": "EBNA-containing chromatin from Raji cells was solubilized by treatment with high concentrations of urea and salt and fractionated by hydroxyapatite chromatography. Fractions eluting at different phosphate concentrations were analysed for the presence of EBNA by means of an anti-EBNA-specific 125I-labelled IgG absorption assay. The antigen was found in fractions containing non-histone chromatin proteins.", "contents": "Studies of Epstein-Barr virus (EBV)-associated nuclear antigen: solubilization from Raji cell chromatin with 5 M-urea-2 M-nacl and fractionation on hydroxyapatite. EBNA-containing chromatin from Raji cells was solubilized by treatment with high concentrations of urea and salt and fractionated by hydroxyapatite chromatography. Fractions eluting at different phosphate concentrations were analysed for the presence of EBNA by means of an anti-EBNA-specific 125I-labelled IgG absorption assay. The antigen was found in fractions containing non-histone chromatin proteins."}
{"id": "PMID:211195", "title": "Persistence of both human cytomegalovirus and Epstein-Barr virus genomes in two human lymphoblastoid cell lines.", "content": "By DNA-DNA reassociation kinetic analysis, less than one genome equivalent per cell of human CMV-DNA was found in two lymphoblastoid cell lines, one derived from the peripheral blood of a congenitally infected male infant at the age of 21 months (D4 cell line), the other obtained by co-cultivation of lethally X-irradiated cells from the 9-month lymphoblastoid cell line previously described by Joncas et al. (1975) with cord blood leukocytes of a female newborn (M1 cell line). Human CMV antigens could not be detected and virus could not be rescued from these cells by co-cultivation with fully permissive human fibroblasts. It may be that the CMV-DNA is defective. Epstein-Barr virus DNA as well as EBNA and EBV-EA antigens were present in these cell lines. Both lines express surface markers characteristic of thymus-independent, B lymphocytes. The CMV-DNA of the CMV-DU strain, isolated from this infant's urine five times successively from the age of 1 day to 30 months, appears to be closely related to the DNA of the AD-169 strain by reciprocal hybridization and by electrophoretic pattern analysis of the restriction enzyme cleavage products. Experimental attempts to transform cord blood leukocytes with this urine strain of CMV before or after u.v. irradiation have so far failed.", "contents": "Persistence of both human cytomegalovirus and Epstein-Barr virus genomes in two human lymphoblastoid cell lines. By DNA-DNA reassociation kinetic analysis, less than one genome equivalent per cell of human CMV-DNA was found in two lymphoblastoid cell lines, one derived from the peripheral blood of a congenitally infected male infant at the age of 21 months (D4 cell line), the other obtained by co-cultivation of lethally X-irradiated cells from the 9-month lymphoblastoid cell line previously described by Joncas et al. (1975) with cord blood leukocytes of a female newborn (M1 cell line). Human CMV antigens could not be detected and virus could not be rescued from these cells by co-cultivation with fully permissive human fibroblasts. It may be that the CMV-DNA is defective. Epstein-Barr virus DNA as well as EBNA and EBV-EA antigens were present in these cell lines. Both lines express surface markers characteristic of thymus-independent, B lymphocytes. The CMV-DNA of the CMV-DU strain, isolated from this infant's urine five times successively from the age of 1 day to 30 months, appears to be closely related to the DNA of the AD-169 strain by reciprocal hybridization and by electrophoretic pattern analysis of the restriction enzyme cleavage products. Experimental attempts to transform cord blood leukocytes with this urine strain of CMV before or after u.v. irradiation have so far failed."}
{"id": "PMID:211196", "title": "Herpes simplex virus type-1 and human lymphocytes: virus expression and the response to infection of adult and foetal cells.", "content": "The growth of Herpes simplex virus type I (HSV-I) in human lymphocytes of adult and foetal origin was studied. Virus DNA synthesis, antigen and particle production and the yield of infectious progeny were determined in cultured lymphocytes with or without exposure to stimulating concentrations of the mitogens phytohaemagglutinin and pokeweed mitogen. Separated sub-populations of cells were examined and the conclusion reached that only the stimulated T-lymphoblast was permissive for full virus expression. Stimulation of cell DNA synthesis in response to infection was observed in cultures of adult and foetal lymphocytes under conditions which were nonpermissive for virus growth. Morphological change and prolonged culture survival were a feature of foetal lymphocytes exposed to u.v. irradiated HSV-I.", "contents": "Herpes simplex virus type-1 and human lymphocytes: virus expression and the response to infection of adult and foetal cells. The growth of Herpes simplex virus type I (HSV-I) in human lymphocytes of adult and foetal origin was studied. Virus DNA synthesis, antigen and particle production and the yield of infectious progeny were determined in cultured lymphocytes with or without exposure to stimulating concentrations of the mitogens phytohaemagglutinin and pokeweed mitogen. Separated sub-populations of cells were examined and the conclusion reached that only the stimulated T-lymphoblast was permissive for full virus expression. Stimulation of cell DNA synthesis in response to infection was observed in cultures of adult and foetal lymphocytes under conditions which were nonpermissive for virus growth. Morphological change and prolonged culture survival were a feature of foetal lymphocytes exposed to u.v. irradiated HSV-I."}
{"id": "PMID:211197", "title": "Herpes simplex virus necleic acid synthesis following infection of non-permissive XC cells.", "content": "DNA hybridization kinetic analysis of cellular DNA following high multiplicity infection of non-permissive XC cells by herpes simplex virus type I showed that HSV DNA penetrates to the nucleus of the cell but that the number of virus DNA copies present in each cell quickly begins to decline. There did not appear to be any net virus DNA synthesis and the loss of virus DNA copies continued until there was approximately one per haploid genome equivalent. HSV-2 likewise did not show any detectable virus DNA replication. The residual virus information was stable for more than 48 h. CsCl density gradient analysis of the infected cell DNA suggested an association between the HSV DNA and that of the cells. Network analysis also supported the suggestion that a stable association between the virus DNA and host DNA begins shortly after infection. Cell division resulted in the segregation of the virus DNA but not its loss from the cell population. Virus-specific RNA synthesis was easily detectable and 40 to 50% of a labelled DNA probe was converted to an RNA:DNA hybrid.", "contents": "Herpes simplex virus necleic acid synthesis following infection of non-permissive XC cells. DNA hybridization kinetic analysis of cellular DNA following high multiplicity infection of non-permissive XC cells by herpes simplex virus type I showed that HSV DNA penetrates to the nucleus of the cell but that the number of virus DNA copies present in each cell quickly begins to decline. There did not appear to be any net virus DNA synthesis and the loss of virus DNA copies continued until there was approximately one per haploid genome equivalent. HSV-2 likewise did not show any detectable virus DNA replication. The residual virus information was stable for more than 48 h. CsCl density gradient analysis of the infected cell DNA suggested an association between the HSV DNA and that of the cells. Network analysis also supported the suggestion that a stable association between the virus DNA and host DNA begins shortly after infection. Cell division resulted in the segregation of the virus DNA but not its loss from the cell population. Virus-specific RNA synthesis was easily detectable and 40 to 50% of a labelled DNA probe was converted to an RNA:DNA hybrid."}
{"id": "PMID:211198", "title": "OK 10 virus, an avian retrovirus resembling the acute leukaemia viruses.", "content": "The OK 10 virus complex was isolated from a liver tumour of a chicken which, as an embryo, had been inoculated intravenously with a field isolate of an avian leukosis virus. The OK 10 virus complex contains at least two viruses: the interference assay and serum neutralization test indicate that the helper virus belongs to subgroup A. One of the viruses, OK 10 V, induces distinct foci in chick embryo cells under agar overlay and cells from the foci form colonies in soft agar. These properties allow in vitro assay of the virus. Injection of virus or infected cells into chicks induces acute leukaemia but no local tumours. Another virus, OK 10 AV (associated virus), comprises about 99% of the OK 10 complex. The virus does not induce foci in chick embryo cells. In chickens it causes leukosis 17 months after injection. Electron micrographs of OK 10 virus stocks show typical C type virus particles. These particles have a density of 1.16 g/ml and contain 70S RNA which, after heat denaturation, releases type b RNA subunits. The OK 10 virus complex apparently represents a strain of acute leukaemia viruses.", "contents": "OK 10 virus, an avian retrovirus resembling the acute leukaemia viruses. The OK 10 virus complex was isolated from a liver tumour of a chicken which, as an embryo, had been inoculated intravenously with a field isolate of an avian leukosis virus. The OK 10 virus complex contains at least two viruses: the interference assay and serum neutralization test indicate that the helper virus belongs to subgroup A. One of the viruses, OK 10 V, induces distinct foci in chick embryo cells under agar overlay and cells from the foci form colonies in soft agar. These properties allow in vitro assay of the virus. Injection of virus or infected cells into chicks induces acute leukaemia but no local tumours. Another virus, OK 10 AV (associated virus), comprises about 99% of the OK 10 complex. The virus does not induce foci in chick embryo cells. In chickens it causes leukosis 17 months after injection. Electron micrographs of OK 10 virus stocks show typical C type virus particles. These particles have a density of 1.16 g/ml and contain 70S RNA which, after heat denaturation, releases type b RNA subunits. The OK 10 virus complex apparently represents a strain of acute leukaemia viruses."}
{"id": "PMID:211199", "title": "A plaque assay for Mount Elgon bat virus based on intrinsic interference.", "content": "A plaque count infectivity assay was developed in which chick cells infected with the Mount Elgon bat virus were completely resistant to superinfection with large doses of Sendai virus. Several variables markedly affected the assay sensitivity. The defined plaque assay was simple, highly reproducible and sensitive. It allowed determination of virus neutralizing antibody in a simple and reproducible test. Both actinomycin D and 5-iododeoxyuridine were without effect on plaque formation.", "contents": "A plaque assay for Mount Elgon bat virus based on intrinsic interference. A plaque count infectivity assay was developed in which chick cells infected with the Mount Elgon bat virus were completely resistant to superinfection with large doses of Sendai virus. Several variables markedly affected the assay sensitivity. The defined plaque assay was simple, highly reproducible and sensitive. It allowed determination of virus neutralizing antibody in a simple and reproducible test. Both actinomycin D and 5-iododeoxyuridine were without effect on plaque formation."}
{"id": "PMID:211200", "title": "Reversion of temperature sensitive transformation mutants of Rous sarcoma virus and its effect on the expression of tumour specific surface antigen.", "content": "Rous sarcoma virus (RSV) mutants, which bear temperature sensitive (ts) defects in both the maintenance of cell transformation and the expression of tumour specific cell surface antigen(s) (TSSA), have yielded a number of revertants. In seven revertants studied, the acquisition of wild type transforming capacities is always accompanied by a wild type TSSA expression. This strongly indicates that transformation and TSSA expression in RSV are affected by the same mutation.", "contents": "Reversion of temperature sensitive transformation mutants of Rous sarcoma virus and its effect on the expression of tumour specific surface antigen. Rous sarcoma virus (RSV) mutants, which bear temperature sensitive (ts) defects in both the maintenance of cell transformation and the expression of tumour specific cell surface antigen(s) (TSSA), have yielded a number of revertants. In seven revertants studied, the acquisition of wild type transforming capacities is always accompanied by a wild type TSSA expression. This strongly indicates that transformation and TSSA expression in RSV are affected by the same mutation."}
{"id": "PMID:211201", "title": "Noradrenaline receptor sensitivity after chronic ethanol administration.", "content": "The effects of the central noradrenaline receptor stimulating agent clonidine on blood pressure, heart rate, and flexor reflex activity were studied in intact rats and in rats chronically treated with ethanol. The clonidine-induced changes were similar in ethanol-treated animals and in animals never subjected to ethanol. The results suggest that the sensitivity of central noradrenaline receptors involved in the mediation of the circulatory changes and of the flexor reflex activity after clonidine is not altered by chronic administration of ethanol.", "contents": "Noradrenaline receptor sensitivity after chronic ethanol administration. The effects of the central noradrenaline receptor stimulating agent clonidine on blood pressure, heart rate, and flexor reflex activity were studied in intact rats and in rats chronically treated with ethanol. The clonidine-induced changes were similar in ethanol-treated animals and in animals never subjected to ethanol. The results suggest that the sensitivity of central noradrenaline receptors involved in the mediation of the circulatory changes and of the flexor reflex activity after clonidine is not altered by chronic administration of ethanol."}
{"id": "PMID:211202", "title": "Physiological properties of afferents and synaptic reorganization in the rat cerebellum degranulated by postnatal X-irradiation.", "content": "Elimination of most granule, basket, and stellate interneurons in the rat cerebellum was achieved by repeated doses of low level x-irradiation applied during the first two weeks of postnatal life. Electrical stimulation of the brain stem and peripheral limbs was employed to investigate the properties of afferent cerebellar pathways and the nature of the reorganized neuronal synaptic circuitry in the degranulated cerebellum of the adult. Direct contacts of mossy fibers on Purkinje cells were indicated by short latency, single spike responses: 1.9 msec from the lateral reticular nucleus of brain stem and 5.4 msec from ipsilpateral forelimb. These were shorter than in normal rats by 0.9 and 2.1 msec, respectively. The topography of projections from peripheral stimulation was approximately normal. Mossy fiber responses followed stimulation at up to 20/sec, whereas climbing fiber pathways fatigued at 10/sec. The latency of climbing fiber input to peripheral limb stimulation in x-irradiated cerebellum was 23 +/- 8 (SD) msec. In x-irradiated rats, the climbing fiber pathways evoked highly variable extracellular burst responses and intracellular EPSPs of different, discrete sizes. These variable responses suggest that multiple climbing fibers contact single Purkinje cells. We conclude that each type of afferent retains identifying characteristics of transmission. However, rules for synaptic specification appear to break down so that: (1) abnormal classes of neurons develop synaptic connections, i.e., mossy fibers to Purkinje cells; (2) incorrect numbers of neurons share postsynaptic targets, i.e., more than one climbing fiber to a Purkinje cell; and (3) inhibitory synaptic actions may be carried out in the absence of the major inhibitory interneurons, i.e., Purkinje cell collaterals may be effective in lieu of basket and stellate cells.", "contents": "Physiological properties of afferents and synaptic reorganization in the rat cerebellum degranulated by postnatal X-irradiation. Elimination of most granule, basket, and stellate interneurons in the rat cerebellum was achieved by repeated doses of low level x-irradiation applied during the first two weeks of postnatal life. Electrical stimulation of the brain stem and peripheral limbs was employed to investigate the properties of afferent cerebellar pathways and the nature of the reorganized neuronal synaptic circuitry in the degranulated cerebellum of the adult. Direct contacts of mossy fibers on Purkinje cells were indicated by short latency, single spike responses: 1.9 msec from the lateral reticular nucleus of brain stem and 5.4 msec from ipsilpateral forelimb. These were shorter than in normal rats by 0.9 and 2.1 msec, respectively. The topography of projections from peripheral stimulation was approximately normal. Mossy fiber responses followed stimulation at up to 20/sec, whereas climbing fiber pathways fatigued at 10/sec. The latency of climbing fiber input to peripheral limb stimulation in x-irradiated cerebellum was 23 +/- 8 (SD) msec. In x-irradiated rats, the climbing fiber pathways evoked highly variable extracellular burst responses and intracellular EPSPs of different, discrete sizes. These variable responses suggest that multiple climbing fibers contact single Purkinje cells. We conclude that each type of afferent retains identifying characteristics of transmission. However, rules for synaptic specification appear to break down so that: (1) abnormal classes of neurons develop synaptic connections, i.e., mossy fibers to Purkinje cells; (2) incorrect numbers of neurons share postsynaptic targets, i.e., more than one climbing fiber to a Purkinje cell; and (3) inhibitory synaptic actions may be carried out in the absence of the major inhibitory interneurons, i.e., Purkinje cell collaterals may be effective in lieu of basket and stellate cells."}
{"id": "PMID:211203", "title": "A biochemical comparison of Xenopus laevis and mammalian myelin from the central and peripheral nervous systems.", "content": "Myelin purified from the central nervous system of Xenopus laevis contained the same major lipid and protein components as human myelin. However, some minor differences in the myelin proteins were noted. The Xenopus basic protein had a higher apparent mol wt. on sodium dodecyl sulfate gels than the corresponding mammalian protein. The absolute specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase in the Xenopus myelin was considerably higher than in mammals. There were differences in the high mol wt. proteins, and the glycoproteins in Xenopus myelin were more heterogeneous than those in mammals. Peripheral myelin from Xenopus sciatic nerve was compared with that from the rat. The lipids in the two types of myelin were similar. There was a major glycoprotein in the Xenopus myelin corresponding to the P0 protein and a basic protein of slightly larger mol wt. than the P1 protein of rat myelin.", "contents": "A biochemical comparison of Xenopus laevis and mammalian myelin from the central and peripheral nervous systems. Myelin purified from the central nervous system of Xenopus laevis contained the same major lipid and protein components as human myelin. However, some minor differences in the myelin proteins were noted. The Xenopus basic protein had a higher apparent mol wt. on sodium dodecyl sulfate gels than the corresponding mammalian protein. The absolute specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase in the Xenopus myelin was considerably higher than in mammals. There were differences in the high mol wt. proteins, and the glycoproteins in Xenopus myelin were more heterogeneous than those in mammals. Peripheral myelin from Xenopus sciatic nerve was compared with that from the rat. The lipids in the two types of myelin were similar. There was a major glycoprotein in the Xenopus myelin corresponding to the P0 protein and a basic protein of slightly larger mol wt. than the P1 protein of rat myelin."}
{"id": "PMID:211204", "title": "Herpes simplex virus types 1 and 2 in organotypic cultures of mouse central and peripheral nervous system. I. Light microscopic observations of myelin degeneration.", "content": "Mature mouse spinal cord-ganglion cultures, which contain both peripheral and central nervous system as one unit, were infected with herpes simplex virus type 1 (HSV 1) or type 2 (HSV 2) and observed by bright field microscopy for up to 72 hours. There was degeneration of both central and peripheral myelin in cultures infected with either virus, but the pattern of peripheral myelin degeneration associated with HSV 1-infected cultures was differrnt from that in HSV 2-infected cultures. Type 1 was charcterized by focal dilatations; type 2 by \"sausage-shaped\" swellings, and the cytopathic effect of HSV 2 both began (6 hours p.i.) and was completed (36 hours p.i.) earlier than in cultures infected with HSV 1 (12 hours and 48 hours p.i. respectively). In central nervous tissue, the apperance of degenerating myelin after infection with HSV 1 was indistinguishable from  that in HSV 2-infected cultures, but the rate of myelin loss was greater in cultures infected with the type 2 virus. Evidence is presented which suggests that, at least in the peripheral nervous system,myelin degeneration did not appear to be dependent on neuronal or axonal dysfunction or death, but was a direct result of virus infection.", "contents": "Herpes simplex virus types 1 and 2 in organotypic cultures of mouse central and peripheral nervous system. I. Light microscopic observations of myelin degeneration. Mature mouse spinal cord-ganglion cultures, which contain both peripheral and central nervous system as one unit, were infected with herpes simplex virus type 1 (HSV 1) or type 2 (HSV 2) and observed by bright field microscopy for up to 72 hours. There was degeneration of both central and peripheral myelin in cultures infected with either virus, but the pattern of peripheral myelin degeneration associated with HSV 1-infected cultures was differrnt from that in HSV 2-infected cultures. Type 1 was charcterized by focal dilatations; type 2 by \"sausage-shaped\" swellings, and the cytopathic effect of HSV 2 both began (6 hours p.i.) and was completed (36 hours p.i.) earlier than in cultures infected with HSV 1 (12 hours and 48 hours p.i. respectively). In central nervous tissue, the apperance of degenerating myelin after infection with HSV 1 was indistinguishable from  that in HSV 2-infected cultures, but the rate of myelin loss was greater in cultures infected with the type 2 virus. Evidence is presented which suggests that, at least in the peripheral nervous system,myelin degeneration did not appear to be dependent on neuronal or axonal dysfunction or death, but was a direct result of virus infection."}
{"id": "PMID:211205", "title": "Morphogenesis of the Hirano body in neurons of the squirrel monkey dorsal horn.", "content": "Electron microscopic investigation of laminae I-III in the lumbosacral region of the squirrel monkey spinal cord has disclosed possible stages in the morphogenesis of the Hirano body. These bodies occur occasionally in nerve cell bodies and dendrites. They are round to oval in shape, measure up to 2.2 micrometer in diameter and are composed of circular layers of 10 nm filaments. In several instances in the present study, Hirano bodies were observed in close association with the Golgi apparatus. Here Golgi-related vesicles were attached to the external surface of the Hirano bodies. In one instance a cluster of developing Hirano bodies of various sizes was observed. The smaller bodies were located nearest the Golgi apparatus while the larger were further away. In this case several short filaments, which may be precursors of the longer filaments which make up the layers of the inclusion, were observed in the cytoplasm between the Golgi cisternae and the smaller Hirano bodies. These observations suggest that the Golgi apparatus plays a major role in the production of the Hirano body. The significance of the occurrence of these inclusions is discussed.", "contents": "Morphogenesis of the Hirano body in neurons of the squirrel monkey dorsal horn. Electron microscopic investigation of laminae I-III in the lumbosacral region of the squirrel monkey spinal cord has disclosed possible stages in the morphogenesis of the Hirano body. These bodies occur occasionally in nerve cell bodies and dendrites. They are round to oval in shape, measure up to 2.2 micrometer in diameter and are composed of circular layers of 10 nm filaments. In several instances in the present study, Hirano bodies were observed in close association with the Golgi apparatus. Here Golgi-related vesicles were attached to the external surface of the Hirano bodies. In one instance a cluster of developing Hirano bodies of various sizes was observed. The smaller bodies were located nearest the Golgi apparatus while the larger were further away. In this case several short filaments, which may be precursors of the longer filaments which make up the layers of the inclusion, were observed in the cytoplasm between the Golgi cisternae and the smaller Hirano bodies. These observations suggest that the Golgi apparatus plays a major role in the production of the Hirano body. The significance of the occurrence of these inclusions is discussed."}
{"id": "PMID:211206", "title": "Schwann cell abnormalities in 2,5-hexanedione neuropathy.", "content": "Distinctive cytoplasmic alterations of Schwann cells were observed by electron microscopy in rats and mice with peripheral neuropathy induced by chronic exposure to 2,5-hexanedione. Pronounced enlargement of Schwann cells was due to accumulation of 100 angstrom cytoplasmic filaments and endoplasmic reticulum and was most often observed after 12--15 weeks exposure to 2,5-hexanedione. Examination of teased nerve fibres revealed segmental demyelination and remyelination involving axons of normal diameter as well as giant axons. The filament disorder induced by 2,5-hexanedione administration is not limited solely to axoplasmic contents. Possible mechanisms of demyelination are discussed and the changes are compared to those observed in human neuropathy for which 2,5-hexanedione appears to be the closest experimental model.", "contents": "Schwann cell abnormalities in 2,5-hexanedione neuropathy. Distinctive cytoplasmic alterations of Schwann cells were observed by electron microscopy in rats and mice with peripheral neuropathy induced by chronic exposure to 2,5-hexanedione. Pronounced enlargement of Schwann cells was due to accumulation of 100 angstrom cytoplasmic filaments and endoplasmic reticulum and was most often observed after 12--15 weeks exposure to 2,5-hexanedione. Examination of teased nerve fibres revealed segmental demyelination and remyelination involving axons of normal diameter as well as giant axons. The filament disorder induced by 2,5-hexanedione administration is not limited solely to axoplasmic contents. Possible mechanisms of demyelination are discussed and the changes are compared to those observed in human neuropathy for which 2,5-hexanedione appears to be the closest experimental model."}
{"id": "PMID:211207", "title": "Inhibition of Na+-K+-activated ATPase activity following experimental spinal cord trauma.", "content": "The specific activity of the membrane-bound enzyme, Na+-K+-activated adenosine triphosphatase (ATPase), has been shown to be decreased following experimental impact injury (400 gm-cm) to the spinal cord in dogs. The prompt and significant (p less than 0.01) fall in activity was evident as early as 5 minutes after injury, and remained at 56% to 67% of control for the 1-hour period studied. This decrease was most prominent in the central core of the traumatized segments of spinal cord. Central core samples, excised immediately adjacent to the trauma site, gave values for the Na+-K+-activated enzyme intermediate to those of the trauma and control sites. For these same samples, the activity of the Mg+2-dependent ATPase did not change appreciably. No alterations were observed in the tissue surrounding the zone of maximum injury at these early time periods. The relationship of membrane-bound enzyme alterations to blood flow, clotting mechanisms, and abnormal free radical reactions are briefly discussed.", "contents": "Inhibition of Na+-K+-activated ATPase activity following experimental spinal cord trauma. The specific activity of the membrane-bound enzyme, Na+-K+-activated adenosine triphosphatase (ATPase), has been shown to be decreased following experimental impact injury (400 gm-cm) to the spinal cord in dogs. The prompt and significant (p less than 0.01) fall in activity was evident as early as 5 minutes after injury, and remained at 56% to 67% of control for the 1-hour period studied. This decrease was most prominent in the central core of the traumatized segments of spinal cord. Central core samples, excised immediately adjacent to the trauma site, gave values for the Na+-K+-activated enzyme intermediate to those of the trauma and control sites. For these same samples, the activity of the Mg+2-dependent ATPase did not change appreciably. No alterations were observed in the tissue surrounding the zone of maximum injury at these early time periods. The relationship of membrane-bound enzyme alterations to blood flow, clotting mechanisms, and abnormal free radical reactions are briefly discussed."}
{"id": "PMID:211208", "title": "Delayed cure of Cushing's disease after transsphenoidal surgery of pituitary microadenomas. Report of two cases.", "content": "Transsphenoidal microdissection has been proposed as a preferred means of treating Cushing's disease. This procedure allows the surgeon to remove a pituitary microadenoma and at the same time to preserve normal tissue. Two cases described here were treated by this method. An interesting and important observation was that neither patient appeared to be cured for 2 to 6 weeks after surgery, as assessed by dexamethasone suppression. Later, normal suppressibility occurred and the course of each patient was compatible with cure. Patients treated by this method should not be automatically retreated because of adrenocorticotropic hormone (ACTH) non-suppressibility in the early postoperative period.", "contents": "Delayed cure of Cushing's disease after transsphenoidal surgery of pituitary microadenomas. Report of two cases. Transsphenoidal microdissection has been proposed as a preferred means of treating Cushing's disease. This procedure allows the surgeon to remove a pituitary microadenoma and at the same time to preserve normal tissue. Two cases described here were treated by this method. An interesting and important observation was that neither patient appeared to be cured for 2 to 6 weeks after surgery, as assessed by dexamethasone suppression. Later, normal suppressibility occurred and the course of each patient was compatible with cure. Patients treated by this method should not be automatically retreated because of adrenocorticotropic hormone (ACTH) non-suppressibility in the early postoperative period."}
{"id": "PMID:211209", "title": "Inhibitory effect of cadmium on vitamin D-stimulated calcium transport in rat duodenum in vitro.", "content": "In vitro effect of cadmium on vitamin D-stimulated calcium transport in the rat was studied using the everted gut sac technique. Calcium transport was significantly inhibited by the addition of cadmium to the mucosal incubation medium. Furthermore, the kinetic analysis of inhibitory effect of cadmium on calcium transport revealed that the type of inhibition was competitive. The apparent \"Km\" and \"Vmax\" value for calcium was 1.0 mM, and 2.86 mumoles ml-1.hr-1, respectively. An apparent \"Ki\" for cadmium was 0.02 mM.", "contents": "Inhibitory effect of cadmium on vitamin D-stimulated calcium transport in rat duodenum in vitro. In vitro effect of cadmium on vitamin D-stimulated calcium transport in the rat was studied using the everted gut sac technique. Calcium transport was significantly inhibited by the addition of cadmium to the mucosal incubation medium. Furthermore, the kinetic analysis of inhibitory effect of cadmium on calcium transport revealed that the type of inhibition was competitive. The apparent \"Km\" and \"Vmax\" value for calcium was 1.0 mM, and 2.86 mumoles ml-1.hr-1, respectively. An apparent \"Ki\" for cadmium was 0.02 mM."}
{"id": "PMID:211214", "title": "Prevalence of growth hormone deficiency in children with cleft lip or palate.", "content": "Two hundred children 7 to 14 years of age with isolated cleft defects of the lip, palate, or both were surveyed for stature. Twelve percent were less than the third percentile in height and were designated \"short.\" All of the short children received an endocrine evaluation. Endogenous growth hormone was examined after two days' pretreatment with stilbesteral. Four of the 25 short children with CLP had total, and four had partial, GH deficiency. Three of the GH-deficient patients were also deficient in ACTH or TSH. In contrast, in a series of 75 short (less than third percentile) children 7 to 14 years of age without cleft defect or other apparent congenital abnormality, only two had total and two had partial GH deficiency. The data suggest that children with isolated CLP have short stature about four times more often, and GH-deficiency about 40 times more often, than children without CLP. The increased prevalence of GH-deficiency may stem from the embryologic relation of adenohypophysis and oral ectoderm.", "contents": "Prevalence of growth hormone deficiency in children with cleft lip or palate. Two hundred children 7 to 14 years of age with isolated cleft defects of the lip, palate, or both were surveyed for stature. Twelve percent were less than the third percentile in height and were designated \"short.\" All of the short children received an endocrine evaluation. Endogenous growth hormone was examined after two days' pretreatment with stilbesteral. Four of the 25 short children with CLP had total, and four had partial, GH deficiency. Three of the GH-deficient patients were also deficient in ACTH or TSH. In contrast, in a series of 75 short (less than third percentile) children 7 to 14 years of age without cleft defect or other apparent congenital abnormality, only two had total and two had partial GH deficiency. The data suggest that children with isolated CLP have short stature about four times more often, and GH-deficiency about 40 times more often, than children without CLP. The increased prevalence of GH-deficiency may stem from the embryologic relation of adenohypophysis and oral ectoderm."}
{"id": "PMID:211215", "title": "Prospective study of enteropathogens in children with diarrhea in Houston and Mexico.", "content": "During a 22-month period, 595 children with diarrhea and 210 age-matched controls attending clinics in Houston (367 children) and Mexico (438) were prospectively evaluated for enteric pathogens. Enteropathogens associated with disease were Shigella (18%), rotavirus (14%), Salmonella (9%), toxigenic Escherichia coli (6%), and others (12%), including 14 Proteus isolates that caused rounding of adrenal cells. Enteropathogens were isolated from a greater (P less than 0.001) number of children with diarrhea (59%) than from asymptomatic controls (6%). Paired sera tested for antibody to heat-labile toxin of E. coli rarely demonstrated a fourfold rise during episodes of diarrhea. This study demonstrates: (1) more striking illness in children from Mexico; (2) more common occurrence of Shigella in Houston, and of rotavirus and Salmonella in Mexico; (3) lack of seasonal occurrence of rotavirus isolation in either population and a summertime occurrence of Shigella in Houston; (4) lack of toxigenic E. coli isolation in endemic diarrhea of either population; and (5) a significant (P less than 0.001) age-related acquisition of E. coli LT antibodies.", "contents": "Prospective study of enteropathogens in children with diarrhea in Houston and Mexico. During a 22-month period, 595 children with diarrhea and 210 age-matched controls attending clinics in Houston (367 children) and Mexico (438) were prospectively evaluated for enteric pathogens. Enteropathogens associated with disease were Shigella (18%), rotavirus (14%), Salmonella (9%), toxigenic Escherichia coli (6%), and others (12%), including 14 Proteus isolates that caused rounding of adrenal cells. Enteropathogens were isolated from a greater (P less than 0.001) number of children with diarrhea (59%) than from asymptomatic controls (6%). Paired sera tested for antibody to heat-labile toxin of E. coli rarely demonstrated a fourfold rise during episodes of diarrhea. This study demonstrates: (1) more striking illness in children from Mexico; (2) more common occurrence of Shigella in Houston, and of rotavirus and Salmonella in Mexico; (3) lack of seasonal occurrence of rotavirus isolation in either population and a summertime occurrence of Shigella in Houston; (4) lack of toxigenic E. coli isolation in endemic diarrhea of either population; and (5) a significant (P less than 0.001) age-related acquisition of E. coli LT antibodies."}
{"id": "PMID:211216", "title": "Extrarenal Wilms tumor.", "content": "The previous reports of extrarenal Wilms tumor are reviewed and two additional patients presented. The clinical and pathologic features are discussed. The diagnosis of extrarenal Wilms tumor does not imply a bad prognosis. Treatment should utilize multidrug chemotherapy similar to the guidelines set by the National Wilms Tumor Study.", "contents": "Extrarenal Wilms tumor. The previous reports of extrarenal Wilms tumor are reviewed and two additional patients presented. The clinical and pathologic features are discussed. The diagnosis of extrarenal Wilms tumor does not imply a bad prognosis. Treatment should utilize multidrug chemotherapy similar to the guidelines set by the National Wilms Tumor Study."}
{"id": "PMID:211221", "title": "Preparation and immunological cross-reactions of penicilloic and penilloic acids.", "content": "Methods are described for the preparation of pure crystalline samples of the penicilloic and penilloic acids of penicillin G, carbenicillin, cloxacillin, floxacillin, methicillin, penicillin V, and ticarcillin and the penicilloic acids of amoxicillin, ampicillin, phenethicillin, and propicillin. The interaction between the compounds and rabbit antibenzylpenicilloyl antibodies was evaluated by hemagglutination inhibition measurements. A significant correlation was found in this system between the reactivity of penicilloic acids and the corresponding penilloic acids; on average, the penicilloic acids were more reactive on a molar basis by a factor of 11. The results are discussed in terms of the general immunochemistry and side-chain structure of the parent penicillins.", "contents": "Preparation and immunological cross-reactions of penicilloic and penilloic acids. Methods are described for the preparation of pure crystalline samples of the penicilloic and penilloic acids of penicillin G, carbenicillin, cloxacillin, floxacillin, methicillin, penicillin V, and ticarcillin and the penicilloic acids of amoxicillin, ampicillin, phenethicillin, and propicillin. The interaction between the compounds and rabbit antibenzylpenicilloyl antibodies was evaluated by hemagglutination inhibition measurements. A significant correlation was found in this system between the reactivity of penicilloic acids and the corresponding penilloic acids; on average, the penicilloic acids were more reactive on a molar basis by a factor of 11. The results are discussed in terms of the general immunochemistry and side-chain structure of the parent penicillins."}
{"id": "PMID:211222", "title": "Steady-state urinary excretion method for determining bioequivalence of conjugated estrogen products.", "content": "The steady-state excretion of conjugated estrogens in the urine of postmenopausal women dosed with conjugated estrogens tablets was studied using a modification of a previously published method. The procedure was used to quantitate the estrogens both before and during conjugated estrogens replacement therapy. The method, which is relatively specific, involves enzyme hydrolysis of urine samples a number of classical extraction and purification steps, and analysis of the silylated estrogens on a 2.7-m, 1.7% diethylene glycol succinate column using flame-ionization detection. The results indicate that steady-state urinary estrogen excretion levels were obtained within 17 days of dosing. Furthermore, the urinary estrogen excretion profile was significantly different from the composition of the estrogens in the dosage form.", "contents": "Steady-state urinary excretion method for determining bioequivalence of conjugated estrogen products. The steady-state excretion of conjugated estrogens in the urine of postmenopausal women dosed with conjugated estrogens tablets was studied using a modification of a previously published method. The procedure was used to quantitate the estrogens both before and during conjugated estrogens replacement therapy. The method, which is relatively specific, involves enzyme hydrolysis of urine samples a number of classical extraction and purification steps, and analysis of the silylated estrogens on a 2.7-m, 1.7% diethylene glycol succinate column using flame-ionization detection. The results indicate that steady-state urinary estrogen excretion levels were obtained within 17 days of dosing. Furthermore, the urinary estrogen excretion profile was significantly different from the composition of the estrogens in the dosage form."}
{"id": "PMID:211224", "title": "Reaction of sodium hydroxymethanesulfonate with substituted anilines.", "content": "The reactions of substituted anilines with sodium hydroxymethanesulfonate to form the anilinomethanesulfonates were studied in 50% ethanol--water at 0--50 degrees. The Arrhenius rate constants were 5.4 X 10(10) exp(--16,400/RT) M-1 min-1 for aniline, 4.8 X 10(11) exp(--17,100RT) M-1 min-1 for p-anisidine, 7.1 X 10(9) exp(--14,500/RT) M-1 min-1 for p-toluidine, 1.5 X 10(13) exp(--21,100/RT) M-1 min-1 for p-chloroaniline, and 1.1 X 10(12) exp(--19,800/RT) M-l min-1 for p-bromoaniline. Some equilibrium constants and hydrolysis rate constants of the products also were calculated. Hydrolysis rate constants were temperature independent. These reactions had a p value of --3.40 in the Hammett equation. The solvent concentrations used proved to be very convenient for obtaining high yields of the aminomethanesulfonates.", "contents": "Reaction of sodium hydroxymethanesulfonate with substituted anilines. The reactions of substituted anilines with sodium hydroxymethanesulfonate to form the anilinomethanesulfonates were studied in 50% ethanol--water at 0--50 degrees. The Arrhenius rate constants were 5.4 X 10(10) exp(--16,400/RT) M-1 min-1 for aniline, 4.8 X 10(11) exp(--17,100RT) M-1 min-1 for p-anisidine, 7.1 X 10(9) exp(--14,500/RT) M-1 min-1 for p-toluidine, 1.5 X 10(13) exp(--21,100/RT) M-1 min-1 for p-chloroaniline, and 1.1 X 10(12) exp(--19,800/RT) M-l min-1 for p-bromoaniline. Some equilibrium constants and hydrolysis rate constants of the products also were calculated. Hydrolysis rate constants were temperature independent. These reactions had a p value of --3.40 in the Hammett equation. The solvent concentrations used proved to be very convenient for obtaining high yields of the aminomethanesulfonates."}
{"id": "PMID:211227", "title": "The pharmacological properties of some crustacean neuronal acetylcholine, gamma-aminobutyric acid, and L-glutamate responses.", "content": "1. A study was performed of the L-glutamate, gamma-aminobutyric acid (GABA), and acetylcholine (ACh) responses of cells in the stomatogastric ganglion of the crab, Cancer pagurus. 2. Ionophoretic or pressure application of L-glutamate revealed three classes of responses: a K+-dependent inhibition which reversed at 15-20 mV more negative than the resting potential; a Cl- dependent inhibitory response which was at equilibrium at the resting potential; and a depolarizing response. 3. Ionophoretic or pressure applications of GABA likewise produced three kinds of responses: an increase in K+ conductance, an increase in Cl- conductance, and a depolarizing response. 4. Picrotoxin (10(-6)-10(-5) M) was effective in blocking both the glutamate inhibitory responses. 10(-4) M-picrotoxin, which was necessary to produce a 50% block of the GABA-K+-dependent response, had no effect on the GABA-Cl- response. 5. beta-Guanidinopropionic acid (beta-GP) was found to be an agonist for the GABA-K+ response, but was ineffective in mimicking or blocking the GABA-Cl- response. 6. ACh applications produced large depolarizing responses with a pharmacological profile similar to that of the nicotinic ganglionic response in vertebrates. 7. The muscarinic agonist, acetyl-beta-methyl choline (MeCh), produced depolarizations which decreased in amplitude as the membrane was hyperpolarized from -40 to -100 mV. Pilocarpine and oxotremorine produced changes in the endogenous activity of ganglionic neurones. 8. Implications of these results for the identification of synaptic transmitters in the somatogastric ganglion are discussed.", "contents": "The pharmacological properties of some crustacean neuronal acetylcholine, gamma-aminobutyric acid, and L-glutamate responses. 1. A study was performed of the L-glutamate, gamma-aminobutyric acid (GABA), and acetylcholine (ACh) responses of cells in the stomatogastric ganglion of the crab, Cancer pagurus. 2. Ionophoretic or pressure application of L-glutamate revealed three classes of responses: a K+-dependent inhibition which reversed at 15-20 mV more negative than the resting potential; a Cl- dependent inhibitory response which was at equilibrium at the resting potential; and a depolarizing response. 3. Ionophoretic or pressure applications of GABA likewise produced three kinds of responses: an increase in K+ conductance, an increase in Cl- conductance, and a depolarizing response. 4. Picrotoxin (10(-6)-10(-5) M) was effective in blocking both the glutamate inhibitory responses. 10(-4) M-picrotoxin, which was necessary to produce a 50% block of the GABA-K+-dependent response, had no effect on the GABA-Cl- response. 5. beta-Guanidinopropionic acid (beta-GP) was found to be an agonist for the GABA-K+ response, but was ineffective in mimicking or blocking the GABA-Cl- response. 6. ACh applications produced large depolarizing responses with a pharmacological profile similar to that of the nicotinic ganglionic response in vertebrates. 7. The muscarinic agonist, acetyl-beta-methyl choline (MeCh), produced depolarizations which decreased in amplitude as the membrane was hyperpolarized from -40 to -100 mV. Pilocarpine and oxotremorine produced changes in the endogenous activity of ganglionic neurones. 8. Implications of these results for the identification of synaptic transmitters in the somatogastric ganglion are discussed."}
{"id": "PMID:211229", "title": "Transmission along and between rods in the tiger salamander retina.", "content": "1. The electrical pathways that couple the rods and that link the outer segments of the rods to the coupled network, were evaluated. Two separate micro-electrodes were inserted into the inner or outer segments of the same or neighbouring rods under visual control. Current was passed through one electrode, and the resulting potential recorded with the other. 2. The input resistance, measured at the inner or outer segment in a rod in the network, is strongly outward rectifying. It is typically near 40 Momega when the membrane is hyperpolarized 10 mV or more by extrinsic current, less than 10 Momega when the membrane is depolarized by 5 mV or more, and near 30 Momega at the no-current level. 3. When current is injected into the outer segment, the response in the inner segment is nearly identical with that at the outer segment, suggesting that the resistance coupling the segments is not high relative to the input resistance of the rod in the network. 4. Under voltage clamp the light response current for a rod in the network is of constant magnitude for potential levels between -80 and -20 mV. This suggests that there is little or no measurable light elicited conductance change associated with the response, possibly a consequence of coupling between rods. 5. The rod response increases with increasing diameter of a concentric test flash up to about 200 micron, or about 16 rod diameters. 6. When current is injected into one rod, the response in its immediate neighbours is between a quarter and one tenth that recorded in the injected rod for all potential levels in the injected rod. 7. The membrane time constant, measured in a rod in the network, is proportional to the voltage-dependent input resistance at 0.16 msec/Momega. With assumptions about the geometry of the rod network this represents a membrane capacitance of 1.5 muF/cm2. 8. The data can be approximated by a network model of square array. The model predicts that: the outer segment contributes less than half the current for the total rod response, the membrane resistance of an individual rod is greater than twice the measured input resistance for the rod in the network, near 60 Momega, and the coupling resistance for each arm of the network is about 4 times the individual rod resistance, near 240 Momega.", "contents": "Transmission along and between rods in the tiger salamander retina. 1. The electrical pathways that couple the rods and that link the outer segments of the rods to the coupled network, were evaluated. Two separate micro-electrodes were inserted into the inner or outer segments of the same or neighbouring rods under visual control. Current was passed through one electrode, and the resulting potential recorded with the other. 2. The input resistance, measured at the inner or outer segment in a rod in the network, is strongly outward rectifying. It is typically near 40 Momega when the membrane is hyperpolarized 10 mV or more by extrinsic current, less than 10 Momega when the membrane is depolarized by 5 mV or more, and near 30 Momega at the no-current level. 3. When current is injected into the outer segment, the response in the inner segment is nearly identical with that at the outer segment, suggesting that the resistance coupling the segments is not high relative to the input resistance of the rod in the network. 4. Under voltage clamp the light response current for a rod in the network is of constant magnitude for potential levels between -80 and -20 mV. This suggests that there is little or no measurable light elicited conductance change associated with the response, possibly a consequence of coupling between rods. 5. The rod response increases with increasing diameter of a concentric test flash up to about 200 micron, or about 16 rod diameters. 6. When current is injected into one rod, the response in its immediate neighbours is between a quarter and one tenth that recorded in the injected rod for all potential levels in the injected rod. 7. The membrane time constant, measured in a rod in the network, is proportional to the voltage-dependent input resistance at 0.16 msec/Momega. With assumptions about the geometry of the rod network this represents a membrane capacitance of 1.5 muF/cm2. 8. The data can be approximated by a network model of square array. The model predicts that: the outer segment contributes less than half the current for the total rod response, the membrane resistance of an individual rod is greater than twice the measured input resistance for the rod in the network, near 60 Momega, and the coupling resistance for each arm of the network is about 4 times the individual rod resistance, near 240 Momega."}
{"id": "PMID:211230", "title": "Regulation by patterned preganglionic neural activity of transmitter stores in a sympathetic ganglion.", "content": "1. The effect of patterned preganglionic stimulation on acetylcholine (ACh) stores was studied in the superior cervical ganglion of the cat. 2. Patterns of stimulation based on 0.5 and 1.0 s trains at frequencies from 10 to 80/s and intervals between trains of 2-180 s increased ACh stores, over periods of 1-3 h stimulation, to the same extent (30-70%) as found earlier to result from continuous stimulation. 3. If the mean frequency of the overall pattern was greater than 5/s the increase in stores developed after termination of the stimulation. If the mean frequency was less than 5/s the increase developed progressively during stimulation and it was then maintained without accommodation over 7 h of stimulation. 4. The magnitude of the increase in ACh stores was linearly related to the frequency within the trains from 10 to 40/s, decreasing with further increase in frequency, and absent below 6-7/s. 5. The ACh stores were increased by patterns of stimulation that mimicked discharging of preganglionic neurones driven by the central respiratory drive under hypercapnic or asphyxial stress; and were increased similarly in animals respired with hypercapnic or partially asphyxial gas mixtures when the preganglionic innervation was intact, but not when it was severed. 6. The variance between ACh stores of ganglia from different animals was reduced in animals held in a controlled environment for 1-2 weeks before experimentation. 7. It is concluded that patterning of preganglionic inputs into high frequency trains is a code for the ongoing modulation of transmitter stores in a sympathetic ganglion. 8. The findings are discussed in relation to current knowledge of ganglionic transmission and to after-hyperpolarization in mammalian unmyelinated nerve fibres.", "contents": "Regulation by patterned preganglionic neural activity of transmitter stores in a sympathetic ganglion. 1. The effect of patterned preganglionic stimulation on acetylcholine (ACh) stores was studied in the superior cervical ganglion of the cat. 2. Patterns of stimulation based on 0.5 and 1.0 s trains at frequencies from 10 to 80/s and intervals between trains of 2-180 s increased ACh stores, over periods of 1-3 h stimulation, to the same extent (30-70%) as found earlier to result from continuous stimulation. 3. If the mean frequency of the overall pattern was greater than 5/s the increase in stores developed after termination of the stimulation. If the mean frequency was less than 5/s the increase developed progressively during stimulation and it was then maintained without accommodation over 7 h of stimulation. 4. The magnitude of the increase in ACh stores was linearly related to the frequency within the trains from 10 to 40/s, decreasing with further increase in frequency, and absent below 6-7/s. 5. The ACh stores were increased by patterns of stimulation that mimicked discharging of preganglionic neurones driven by the central respiratory drive under hypercapnic or asphyxial stress; and were increased similarly in animals respired with hypercapnic or partially asphyxial gas mixtures when the preganglionic innervation was intact, but not when it was severed. 6. The variance between ACh stores of ganglia from different animals was reduced in animals held in a controlled environment for 1-2 weeks before experimentation. 7. It is concluded that patterning of preganglionic inputs into high frequency trains is a code for the ongoing modulation of transmitter stores in a sympathetic ganglion. 8. The findings are discussed in relation to current knowledge of ganglionic transmission and to after-hyperpolarization in mammalian unmyelinated nerve fibres."}
{"id": "PMID:211231", "title": "Target tissues for relaxin identified in vitro with 125I-labelled porcine relaxin.", "content": "Various tissues from the mouse, rat and guinea-pig were used to examine the binding of a biologically active, esterified and 125I-labelled porcine relaxin. Binding to mouse symphysial homogenates was time- and temperature-dependent. Other peptide hormones did not complete with relaxin for binding. Mouse uterine tissue displayed similar binding characteristics. Fractionated mammary tissue from 15- and 20-day-pregnant rats exhibited significant relaxin binding activity, as did homogenates of the guinea-pig public symphysis and cervix. Under the conditions used, no relaxin receptors were noted in the liver, spleen or heart from any of the species investigated.", "contents": "Target tissues for relaxin identified in vitro with 125I-labelled porcine relaxin. Various tissues from the mouse, rat and guinea-pig were used to examine the binding of a biologically active, esterified and 125I-labelled porcine relaxin. Binding to mouse symphysial homogenates was time- and temperature-dependent. Other peptide hormones did not complete with relaxin for binding. Mouse uterine tissue displayed similar binding characteristics. Fractionated mammary tissue from 15- and 20-day-pregnant rats exhibited significant relaxin binding activity, as did homogenates of the guinea-pig public symphysis and cervix. Under the conditions used, no relaxin receptors were noted in the liver, spleen or heart from any of the species investigated."}
{"id": "PMID:211232", "title": "Binding of 125I-labelled FSH in the mouse testis in vitro.", "content": "In-vivo testicular binding of highly purified pituitary FSH, labelled by a method which did not significantly affect biological potency, was hormone-specific, tissue-specific and dose-dependent. Hypophysectomy of mice was followed by a progressive increase in the amount of 125I-labelled FSH per unit weight of testis but not in the total amount of hormone taken up by the testis. Maximum binding occurred at 4 h in a membrane-containing fraction prepared by high-speed ultracentrifugation of testicular homogenate. This is considerably later than has been reported for testicular tissue incubated in vitro at 37 degrees C.", "contents": "Binding of 125I-labelled FSH in the mouse testis in vitro. In-vivo testicular binding of highly purified pituitary FSH, labelled by a method which did not significantly affect biological potency, was hormone-specific, tissue-specific and dose-dependent. Hypophysectomy of mice was followed by a progressive increase in the amount of 125I-labelled FSH per unit weight of testis but not in the total amount of hormone taken up by the testis. Maximum binding occurred at 4 h in a membrane-containing fraction prepared by high-speed ultracentrifugation of testicular homogenate. This is considerably later than has been reported for testicular tissue incubated in vitro at 37 degrees C."}
{"id": "PMID:211234", "title": "Synthesis and antiviral acticity of some phosphates of the broad-spectrum antiviral nucleoside, 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin).", "content": "1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide 5'-phosphate (2) was prepared and converted into the following derivatives: the 5'-phosphoramidate 3, the 5'-diphosphate 4, the 5'-triphosphate 5, and the cyclic 3',5'-phosphate 6. The cyclic 2',3'-phosphate 7 was prepared from the parent nucleoside, 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (1), and was opened to the 2'(3')-phosphate 8. These compounds were found to exhibit significant antiviral activity against several viruses in cell culture. Ribavirin 5'-phosphate (2) was shown to be effective when tested against lethal infections in mice caused by influenza A2, influenza B, and murine hepatitis viruses.", "contents": "Synthesis and antiviral acticity of some phosphates of the broad-spectrum antiviral nucleoside, 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin). 1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide 5'-phosphate (2) was prepared and converted into the following derivatives: the 5'-phosphoramidate 3, the 5'-diphosphate 4, the 5'-triphosphate 5, and the cyclic 3',5'-phosphate 6. The cyclic 2',3'-phosphate 7 was prepared from the parent nucleoside, 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (1), and was opened to the 2'(3')-phosphate 8. These compounds were found to exhibit significant antiviral activity against several viruses in cell culture. Ribavirin 5'-phosphate (2) was shown to be effective when tested against lethal infections in mice caused by influenza A2, influenza B, and murine hepatitis viruses."}
{"id": "PMID:211235", "title": "Synthesis and biological activity of new 2-nitroimidazole derivatives.", "content": "In an earlier paper we described the synthesis and the antitrichomonas activity of 2-nitro-alpha,alpha,1-trimethyl-1H-imidazole-5-methanol (2). Starting from this compound, several derivatives have been synthesized. Among these, the phenyl carbonate 8 has been shown to possess activity equal to that of 2 and to be less toxic. This compound therefore is interesting in comparison with some antitrichomonas agents currently in use clinically. Before undertaking an in-depth investigation, compound 8 was subjected to some studies to see whether it has any effects on the central nervous system (CNS). Preliminary results show that, at therapeutic doses, it might induce unwanted CNS effects to a lesser degree than metronidazole.", "contents": "Synthesis and biological activity of new 2-nitroimidazole derivatives. In an earlier paper we described the synthesis and the antitrichomonas activity of 2-nitro-alpha,alpha,1-trimethyl-1H-imidazole-5-methanol (2). Starting from this compound, several derivatives have been synthesized. Among these, the phenyl carbonate 8 has been shown to possess activity equal to that of 2 and to be less toxic. This compound therefore is interesting in comparison with some antitrichomonas agents currently in use clinically. Before undertaking an in-depth investigation, compound 8 was subjected to some studies to see whether it has any effects on the central nervous system (CNS). Preliminary results show that, at therapeutic doses, it might induce unwanted CNS effects to a lesser degree than metronidazole."}
{"id": "PMID:211236", "title": "The role of cyclic AMP in parathyroid hormone action in the toad bladder.", "content": "Parathyroid hormone (PTH) inhibited active transport of inorganic phosphate and stimulated an increase in cyclic AMP concentration in the urinary bladder of the toad, Bufo marinus. Active transport of phosphate in the toad bladder was also inhibited by an analog of cyclic AMP (dibutyryl cyclic AMP) and by other drugs (pitressin and theophylline) which increase toad bladder intracellular cyclic AMP concentration. These data support the concept that cyclic AMP may be the mediator of PTH-induced phosphate transport inhibition in the toad bladder.", "contents": "The role of cyclic AMP in parathyroid hormone action in the toad bladder. Parathyroid hormone (PTH) inhibited active transport of inorganic phosphate and stimulated an increase in cyclic AMP concentration in the urinary bladder of the toad, Bufo marinus. Active transport of phosphate in the toad bladder was also inhibited by an analog of cyclic AMP (dibutyryl cyclic AMP) and by other drugs (pitressin and theophylline) which increase toad bladder intracellular cyclic AMP concentration. These data support the concept that cyclic AMP may be the mediator of PTH-induced phosphate transport inhibition in the toad bladder."}
{"id": "PMID:211242", "title": "Demonstration of Marek's disease tumor-associated surface antigen in chickens infected with nononcogenic Marek's disease virus and herpesvirus of turkeys.", "content": "The presence of Marek's disease tumor-associated surface antigen (MATSA) was demonstrated on spleen cells from P-line chickens inoculated 5--6 days earlier with herpesvirus of turkeys and SB-1 (a nononcogenic Marek's disease virus). Antisera against MATSA expressed on five Marek's disease lymphoblastoid cell lines were able to recognize the MATSA present on SB-1-infected spleen cells. No viral membrane antigens and only a low incidence of viral internal antigens could be demonstrated.", "contents": "Demonstration of Marek's disease tumor-associated surface antigen in chickens infected with nononcogenic Marek's disease virus and herpesvirus of turkeys. The presence of Marek's disease tumor-associated surface antigen (MATSA) was demonstrated on spleen cells from P-line chickens inoculated 5--6 days earlier with herpesvirus of turkeys and SB-1 (a nononcogenic Marek's disease virus). Antisera against MATSA expressed on five Marek's disease lymphoblastoid cell lines were able to recognize the MATSA present on SB-1-infected spleen cells. No viral membrane antigens and only a low incidence of viral internal antigens could be demonstrated."}
{"id": "PMID:211243", "title": "Ependymomas, malignant tumors of pancreatic islets, and osteosarcomas induced in hamsters by BK virus, a human papovavirus.", "content": "BK virus (BKV), a human papovavirus, was inoculated iv into 3-week-old Syrian golden hamsters. Between 2 1/2 and 9 months after inoculation, 82% of the animals developed tumors. The induced neoplasms were ependymoma, carcinoma of the pancreatic islets, osteosarcoma, adenocarcinoma, angiosarcoma, angioma, lymphoma, and seminoma. Hypersecretion of insulin, glucagon, C-peptide, and calcitonin was detected in tumors of pancreatic islets. BKV etiology of tumors was supported by the following evidence: 1) No tumors with BKV-specific markers appeared in animals given injections of buffer, animals inoculated with BKV neutralized by anti-BKV-specific serum, or uninoculated controls; 2) BKV tumor (T) antigen was detected by immunofluorescence and complement fixation tests in tumors of animals inoculated with infectious BKV and in transplanted tumors; 3) antibodies to BKV T-antigen were detected in sera of animals bearing primary or transplanted tumors; 4) BKV could be activated by Sendai virus-mediated fusion of neoplastic cells with susceptible Vero cells; and 5) no endogenous hamster oncornaviruses were found in tumors.", "contents": "Ependymomas, malignant tumors of pancreatic islets, and osteosarcomas induced in hamsters by BK virus, a human papovavirus. BK virus (BKV), a human papovavirus, was inoculated iv into 3-week-old Syrian golden hamsters. Between 2 1/2 and 9 months after inoculation, 82% of the animals developed tumors. The induced neoplasms were ependymoma, carcinoma of the pancreatic islets, osteosarcoma, adenocarcinoma, angiosarcoma, angioma, lymphoma, and seminoma. Hypersecretion of insulin, glucagon, C-peptide, and calcitonin was detected in tumors of pancreatic islets. BKV etiology of tumors was supported by the following evidence: 1) No tumors with BKV-specific markers appeared in animals given injections of buffer, animals inoculated with BKV neutralized by anti-BKV-specific serum, or uninoculated controls; 2) BKV tumor (T) antigen was detected by immunofluorescence and complement fixation tests in tumors of animals inoculated with infectious BKV and in transplanted tumors; 3) antibodies to BKV T-antigen were detected in sera of animals bearing primary or transplanted tumors; 4) BKV could be activated by Sendai virus-mediated fusion of neoplastic cells with susceptible Vero cells; and 5) no endogenous hamster oncornaviruses were found in tumors."}
{"id": "PMID:211244", "title": "Preparation of plasma membranes from line 10 and line 1 guinea pig hepatomas.", "content": "Gentle homogenization followed by differential and density gradient centrifugation was used to purify line 10 and line 1 guinea pig hepatoma plasma membranes in the form of ghosts. Yields of 15--25% allowed enough membranes to be obtained from a single ascites tumor-bearing animal for immunologic and biochemical studies. Although the plasma membrane marker enzyme (Na+ + k+)atpase was present in normal concentrations in both line 10 and line 1 hepatomas, 5'-nucleotidase was reduced over 100-fold in both tumors and phosphodiesterase I was increased 210-fold in the line 10 hepatomas.", "contents": "Preparation of plasma membranes from line 10 and line 1 guinea pig hepatomas. Gentle homogenization followed by differential and density gradient centrifugation was used to purify line 10 and line 1 guinea pig hepatoma plasma membranes in the form of ghosts. Yields of 15--25% allowed enough membranes to be obtained from a single ascites tumor-bearing animal for immunologic and biochemical studies. Although the plasma membrane marker enzyme (Na+ + k+)atpase was present in normal concentrations in both line 10 and line 1 hepatomas, 5'-nucleotidase was reduced over 100-fold in both tumors and phosphodiesterase I was increased 210-fold in the line 10 hepatomas."}
{"id": "PMID:211245", "title": "The effect of radiotherapy in the treatment of adenoid cystic carcinoma of the head and neck arising in minor salivary glands.", "content": "Eighteen cases of adenoid cystic carcinoma of the minor salivary glands are reviewed. Noteworthy in the history is the report of pain at the site of the lesion which radiates elsewhere, or of numbers or tingling in its area. Radiation therapy is as able to control the primary as local surgery. Involvement of a much wider field than is required to treat the primary may control the perineural spread common to this tumor and avoid the massive procedures necessary to cure it by surgical means. Metastases to the lung, bone, and brain by venous spread can probably be avoided only by early diagnosis.", "contents": "The effect of radiotherapy in the treatment of adenoid cystic carcinoma of the head and neck arising in minor salivary glands. Eighteen cases of adenoid cystic carcinoma of the minor salivary glands are reviewed. Noteworthy in the history is the report of pain at the site of the lesion which radiates elsewhere, or of numbers or tingling in its area. Radiation therapy is as able to control the primary as local surgery. Involvement of a much wider field than is required to treat the primary may control the perineural spread common to this tumor and avoid the massive procedures necessary to cure it by surgical means. Metastases to the lung, bone, and brain by venous spread can probably be avoided only by early diagnosis."}
{"id": "PMID:211246", "title": "Herpesvirus infection modifies adenovirus RNA metabolism in adenovirus type 5-transformed cells.", "content": "The effect of herpes simplex virus (HSV) infection of mRNA metabolism was examined in a system where the fate of specific RNA sequence can be assayed. Adenovirus type 5-transformed rat embryo cell line 107 synthesizes adenovirus-specific RNA (ad-RNA), which functions in the cytoplasm as mRNA. We have utilized ad-RNA as a model for mRNA metabolism, and in a preliminiary study we characterized ad-RNA in the nucleus and cytoplasm by hybridization to filter-bound adenovirus DNA. The results indicated the as-RNA accumulates in the nucleus and that cytoplasmic polyadenylic acid [poly(A)]-containing ad-RNA turns over with a half-life of a few hours. Pulse-chase experiments confirmed these observations and a half-life of about h was determined for the poly(A)-containing cytoplasmic ad-RNA. A second class of ad-RNA remains in the nucleus, where it turns over with a longer hlaf-life (about 24 h). The infection of 107 cells by HSV was restricted at 37 degree C, giving a burst size of 5 PFU per cell and allowing continued host DNA synthesis. Protein synthesis was inhibited greater than 50% by 7 h after infection, and total RNA synthesis was 50% inhibited by 4 h after infection. During the first 8 h after infection, HSV has little effect on the rate of synthesis of ad-RNA as determined by hybridization of nuclear RNA samples, but,during the same period, HSV inhibits the accumulation of poly(A)-containing ad-RNA in the cytoplasm. The degree of this inhibition increases steadily throughout this period and reaches 60% by 6.5 to 8 h after infection. Nosignificant effect was seen on the accumulation of total cellular poly(A)-containing RNA. It was concluded from these experiments that HSV infection alters the metabolism of ad-RNA so as to prevent the normal appearance of the poly(A)-containing mRNA in the cytoplasm. The result for ad-RNA may not represent the behavior of total cellular poly(A)-containing RNA under conditions where infection is restricted.", "contents": "Herpesvirus infection modifies adenovirus RNA metabolism in adenovirus type 5-transformed cells. The effect of herpes simplex virus (HSV) infection of mRNA metabolism was examined in a system where the fate of specific RNA sequence can be assayed. Adenovirus type 5-transformed rat embryo cell line 107 synthesizes adenovirus-specific RNA (ad-RNA), which functions in the cytoplasm as mRNA. We have utilized ad-RNA as a model for mRNA metabolism, and in a preliminiary study we characterized ad-RNA in the nucleus and cytoplasm by hybridization to filter-bound adenovirus DNA. The results indicated the as-RNA accumulates in the nucleus and that cytoplasmic polyadenylic acid [poly(A)]-containing ad-RNA turns over with a half-life of a few hours. Pulse-chase experiments confirmed these observations and a half-life of about h was determined for the poly(A)-containing cytoplasmic ad-RNA. A second class of ad-RNA remains in the nucleus, where it turns over with a longer hlaf-life (about 24 h). The infection of 107 cells by HSV was restricted at 37 degree C, giving a burst size of 5 PFU per cell and allowing continued host DNA synthesis. Protein synthesis was inhibited greater than 50% by 7 h after infection, and total RNA synthesis was 50% inhibited by 4 h after infection. During the first 8 h after infection, HSV has little effect on the rate of synthesis of ad-RNA as determined by hybridization of nuclear RNA samples, but,during the same period, HSV inhibits the accumulation of poly(A)-containing ad-RNA in the cytoplasm. The degree of this inhibition increases steadily throughout this period and reaches 60% by 6.5 to 8 h after infection. Nosignificant effect was seen on the accumulation of total cellular poly(A)-containing RNA. It was concluded from these experiments that HSV infection alters the metabolism of ad-RNA so as to prevent the normal appearance of the poly(A)-containing mRNA in the cytoplasm. The result for ad-RNA may not represent the behavior of total cellular poly(A)-containing RNA under conditions where infection is restricted."}
{"id": "PMID:211247", "title": "Photochemical addition of the cross-linking reagent 4,5', 8-trimethylpsoralen (trioxaslen) to intracellular and viral simian virus 40 DNA-histone complexes.", "content": "We demonstrated here that 4,5', 8-trimethylpsoralen (trioxsalen) is a valuable probe for the structure of SV40 DNA-histone complexes. Trioxsalen readily penetrated intact cells and, in the presence of 340- to 380-nm light, covalently cross-linked DNA preferentially at the sites available for micrococcal nuclease digestion. Histograms of the lengths of the regions of SV40 DNA protected from cross-linking, as visualized by electron microscopy, indicated a repeating pattern of base pairs in DNA from both infected cells and virus particles. The ability of the trioxsalen probe to act in vivo and to map the location of protected  regions may provide a powerful tool for analyzing the role of nucleosomes in the structure of the virus particle and in intracellular complexes such as transcription templates and replication intermediates.", "contents": "Photochemical addition of the cross-linking reagent 4,5', 8-trimethylpsoralen (trioxaslen) to intracellular and viral simian virus 40 DNA-histone complexes. We demonstrated here that 4,5', 8-trimethylpsoralen (trioxsalen) is a valuable probe for the structure of SV40 DNA-histone complexes. Trioxsalen readily penetrated intact cells and, in the presence of 340- to 380-nm light, covalently cross-linked DNA preferentially at the sites available for micrococcal nuclease digestion. Histograms of the lengths of the regions of SV40 DNA protected from cross-linking, as visualized by electron microscopy, indicated a repeating pattern of base pairs in DNA from both infected cells and virus particles. The ability of the trioxsalen probe to act in vivo and to map the location of protected  regions may provide a powerful tool for analyzing the role of nucleosomes in the structure of the virus particle and in intracellular complexes such as transcription templates and replication intermediates."}
{"id": "PMID:211248", "title": "Oncogenicity of AKR endogenous leukemia viruses.", "content": "Four biologically distinct groups of endogenous murine leukemia virus (MuLV) have been isolated from AKR mice. These viruses included (i) ecotopic XC+ MuLV that occur in high titer in normal tissues and serum of AKR mice throughout their life span, (ii) ecotropic XC- MuLV that are produced in high titers by leukemia cells, (iii) xenotropic MuLV that are readily demonstrable only in aged mice, and (iv) polytropic MuLV thatarise in the thymuses of aged mice as a consequence of genetic recombination between ecotropic and xenotropic MuLV. Virus of each of  these biological classes were assayed in AKR mice for their ability to accelerate the occurrence of spontaneous leukemia. Certain isolates of ecotropic XC- MuLV and polytropic MuLV were found to have high oncogenic activity. These viruses induced 100% leukemias within 90 days of inoculation. In contrast, ecotropic XC+ MuLV that were obtained from AKR embryo fibroblasts and xenotropic MuLV that were obtained from the lymphoid tissues of aged AKR mice did not demonstrate oncogenic activity. These findings demonstrate fundamental differences between XC- and XC+ ecotropic MuLV that are found in leukemic and normal tissues, respectively. Furthermore, these findings point to the role of ecotropic XC- and polytropic MuLV in the spontaneous leukemogenesis of AKR mice.", "contents": "Oncogenicity of AKR endogenous leukemia viruses. Four biologically distinct groups of endogenous murine leukemia virus (MuLV) have been isolated from AKR mice. These viruses included (i) ecotopic XC+ MuLV that occur in high titer in normal tissues and serum of AKR mice throughout their life span, (ii) ecotropic XC- MuLV that are produced in high titers by leukemia cells, (iii) xenotropic MuLV that are readily demonstrable only in aged mice, and (iv) polytropic MuLV thatarise in the thymuses of aged mice as a consequence of genetic recombination between ecotropic and xenotropic MuLV. Virus of each of  these biological classes were assayed in AKR mice for their ability to accelerate the occurrence of spontaneous leukemia. Certain isolates of ecotropic XC- MuLV and polytropic MuLV were found to have high oncogenic activity. These viruses induced 100% leukemias within 90 days of inoculation. In contrast, ecotropic XC+ MuLV that were obtained from AKR embryo fibroblasts and xenotropic MuLV that were obtained from the lymphoid tissues of aged AKR mice did not demonstrate oncogenic activity. These findings demonstrate fundamental differences between XC- and XC+ ecotropic MuLV that are found in leukemic and normal tissues, respectively. Furthermore, these findings point to the role of ecotropic XC- and polytropic MuLV in the spontaneous leukemogenesis of AKR mice."}
{"id": "PMID:211249", "title": "Isolation and preliminary characterization of temperature-sensitive mutants of encephalomyocarditis virus.", "content": "Thirty temperature-sensitive mutants of encephalomyocarditis virus have been isolated and partially characterized. Fifteen of these mutants are phenotypically RNA+ thirteen are RNA-, and two are RNA +/-. Six RNA + mutants, one RNA- mutants, and one RNA +/- mutant have virions which are more thermosensitive at 56 degree C than the wild-type virions. Hela cells infected at the nonpermissive temperature with any of the RNA+ mutants produced neither infective nor noninfective viral particles. The cleavage of the precursor polypeptides in cells infected with 11 of the RNA+ mutants was defective at the nonpermissive temperature. This defect in cleavage occurred only in those precursor polypeptides leading to capsid proteins.", "contents": "Isolation and preliminary characterization of temperature-sensitive mutants of encephalomyocarditis virus. Thirty temperature-sensitive mutants of encephalomyocarditis virus have been isolated and partially characterized. Fifteen of these mutants are phenotypically RNA+ thirteen are RNA-, and two are RNA +/-. Six RNA + mutants, one RNA- mutants, and one RNA +/- mutant have virions which are more thermosensitive at 56 degree C than the wild-type virions. Hela cells infected at the nonpermissive temperature with any of the RNA+ mutants produced neither infective nor noninfective viral particles. The cleavage of the precursor polypeptides in cells infected with 11 of the RNA+ mutants was defective at the nonpermissive temperature. This defect in cleavage occurred only in those precursor polypeptides leading to capsid proteins."}
{"id": "PMID:211250", "title": "Characterization of a DNA-protein complex and capsomere subunits derived from polyoma virus by treatment with ethyleneglycol-bis-N,N'-tetraacetic acid and dithiothreitol.", "content": "Treatment of polyoma virions with ethyleneglycol-bil-N,N'-tetraacetic acid (EGTA) and dithiothreitol (DTT) at pH 8.5 resulted in the dissociation of the virions into a DNA-protein complex and individual structural capsomere subunits. The sedimentation value of the DNA-protein complex in sucrose gradients was approximately 48S, and it had a density of 1.45 g/cm3 in equilibrium CsCl gradients. Alkaline sucrose analysis of the DNA within this DNA-protein complex demonstrated that approximately 75% of the DNA is component 1. The proteins associated with the DNA were dissociated by treatment with either NaCl or the anionic detergent Sarkosyl. VP1 and the histone proteins VP 4--7 were the major proteins associated with the DNA. Treatment of the DNA-protein complex with alkaline pH resulted in the specific removal of FP1. Electron microscopy of the 48S DNA-protein complex demonstrated that it is a very tightly coiled structure that is slightly larger than the intact virion. Treatment of the complex with either NaCl or with pH 10.5 buffer resulted in the loss of protein and subsequent loosening of the DNA-protein complex such that the DNA could be visualized. The capsomere subunits released as a result of the EGTA-DTT treatment sedimented as 18S, 12S, and 5S subunits in sucrose gradients. Electrophoretic analysis of the isolated capsomeres demonstrated that VP1, VP2, and VP3 were present in each species, although the ratios of the proteins varied. In addition to the structural proteins, histones VP 4--7 were found to be predominantly associated with the 5S capsomere subunit.", "contents": "Characterization of a DNA-protein complex and capsomere subunits derived from polyoma virus by treatment with ethyleneglycol-bis-N,N'-tetraacetic acid and dithiothreitol. Treatment of polyoma virions with ethyleneglycol-bil-N,N'-tetraacetic acid (EGTA) and dithiothreitol (DTT) at pH 8.5 resulted in the dissociation of the virions into a DNA-protein complex and individual structural capsomere subunits. The sedimentation value of the DNA-protein complex in sucrose gradients was approximately 48S, and it had a density of 1.45 g/cm3 in equilibrium CsCl gradients. Alkaline sucrose analysis of the DNA within this DNA-protein complex demonstrated that approximately 75% of the DNA is component 1. The proteins associated with the DNA were dissociated by treatment with either NaCl or the anionic detergent Sarkosyl. VP1 and the histone proteins VP 4--7 were the major proteins associated with the DNA. Treatment of the DNA-protein complex with alkaline pH resulted in the specific removal of FP1. Electron microscopy of the 48S DNA-protein complex demonstrated that it is a very tightly coiled structure that is slightly larger than the intact virion. Treatment of the complex with either NaCl or with pH 10.5 buffer resulted in the loss of protein and subsequent loosening of the DNA-protein complex such that the DNA could be visualized. The capsomere subunits released as a result of the EGTA-DTT treatment sedimented as 18S, 12S, and 5S subunits in sucrose gradients. Electrophoretic analysis of the isolated capsomeres demonstrated that VP1, VP2, and VP3 were present in each species, although the ratios of the proteins varied. In addition to the structural proteins, histones VP 4--7 were found to be predominantly associated with the 5S capsomere subunit."}
{"id": "PMID:211251", "title": "Measurements of the molecular size of the simian virus 40 large T antigen.", "content": "A measure of the molecular weight of the large simian virus 40 T antigen was sought by SDS-polyacrylamide gel electrophoresis, random-coil chromatography, and sedimentation-velocity analysis in a density gradient. Large T antigen obtained from a simian virus 40-transformed human cell line either by immunoprecipitation or by standard preparatory methods migrated like a 94,000-molecular-weight (approximately  94K) polypeptide in SDS-gels but was found to have an approximate was observed with T antigen obtained from lytically infected monkey cells. In view of the strong theoretical basis for the guanidine method and the agreement with the sedimentation data, these findings suggest that the molecular weight of this protein is approximately 75 to 80K as opposed to 94 to 100K and, therefore, that considerably less than the entire early region of simian virus 40 is required to encode it. This size estimate is in keeping with earlier results which revealed a normal-size T antigen in cells infected with viable deletion mutants lacking as much as 10% of the early region.", "contents": "Measurements of the molecular size of the simian virus 40 large T antigen. A measure of the molecular weight of the large simian virus 40 T antigen was sought by SDS-polyacrylamide gel electrophoresis, random-coil chromatography, and sedimentation-velocity analysis in a density gradient. Large T antigen obtained from a simian virus 40-transformed human cell line either by immunoprecipitation or by standard preparatory methods migrated like a 94,000-molecular-weight (approximately  94K) polypeptide in SDS-gels but was found to have an approximate was observed with T antigen obtained from lytically infected monkey cells. In view of the strong theoretical basis for the guanidine method and the agreement with the sedimentation data, these findings suggest that the molecular weight of this protein is approximately 75 to 80K as opposed to 94 to 100K and, therefore, that considerably less than the entire early region of simian virus 40 is required to encode it. This size estimate is in keeping with earlier results which revealed a normal-size T antigen in cells infected with viable deletion mutants lacking as much as 10% of the early region."}
{"id": "PMID:211252", "title": "Purification of virus-specific RNA from chicken cells infected with avian sarcoma virus: identification of genome-length and subgenome-leghth viral RNAs.", "content": "Avian sarcoma virus (ASV)-specific RNA was purified from ASV-infected cells by using hybridization techniques which employ polydeoxycytidylic acid-elongated DNA complementary to ASV RNA as well as chromatography on polyinosinic acid-Sephadex columns. The purity and nucleotide sequence composition of purified, virus-specific RNA were established by rehybridization experiments and analysis of labeled RNase T1-resistant oligonucleotides by two-dimensional polyacrylamide gel electrophoresis. Polyadenylic acid-containing RNA purified from ASV-infected cells contained approximately 1 to 4% virus-specific RNA, compared with 0.06 to 0.15% observed in uninfected cells. Sucrose gradient analysis of virus-specific RNA isolated from ASV-infected cells revealed two major classes of polyadenylated viral RNA with sedimentation values of 36S and 26-28S. Cells infected with transformation-defective ASV (virus containing a deletion of the sarcoma gene) contained 34S and 20-22S viral RNA species. Double-label experiments employing infected cells labeled initially for 48 h with [3H]uridine and then for either 30, 60, or 240 min with [32P]phosphate showed that the intracellular accumulation of genome-length RNA (36S) was significantly faster than that of the 26-28S viral RNA species.", "contents": "Purification of virus-specific RNA from chicken cells infected with avian sarcoma virus: identification of genome-length and subgenome-leghth viral RNAs. Avian sarcoma virus (ASV)-specific RNA was purified from ASV-infected cells by using hybridization techniques which employ polydeoxycytidylic acid-elongated DNA complementary to ASV RNA as well as chromatography on polyinosinic acid-Sephadex columns. The purity and nucleotide sequence composition of purified, virus-specific RNA were established by rehybridization experiments and analysis of labeled RNase T1-resistant oligonucleotides by two-dimensional polyacrylamide gel electrophoresis. Polyadenylic acid-containing RNA purified from ASV-infected cells contained approximately 1 to 4% virus-specific RNA, compared with 0.06 to 0.15% observed in uninfected cells. Sucrose gradient analysis of virus-specific RNA isolated from ASV-infected cells revealed two major classes of polyadenylated viral RNA with sedimentation values of 36S and 26-28S. Cells infected with transformation-defective ASV (virus containing a deletion of the sarcoma gene) contained 34S and 20-22S viral RNA species. Double-label experiments employing infected cells labeled initially for 48 h with [3H]uridine and then for either 30, 60, or 240 min with [32P]phosphate showed that the intracellular accumulation of genome-length RNA (36S) was significantly faster than that of the 26-28S viral RNA species."}
{"id": "PMID:211253", "title": "Anatomy of bovine mammillitis DNA II. Size and arrangements of the deoxynucleotide sequences.", "content": "We previously reported that bovine mammillitis virus (BMV) DNA consists of two covalently linked components designated L and S and estimated to be 71.5 x 10(6) and 15.7 x 10(6) in molecular weight, respectively; the components invert relative to each other, giving rise to four equimolar populations differing soley in the relative orientation of the two components. We now report that (i) BMV DNA has a contour length corresponding to a molecular weight of 89 x 10(6). (ii) Component L consists of a unique sequence (Ul) bracketed by sequences ab and its inverted repeat b'a', estimated to be of molecular weights 66.1 x 10(6), 2.7 x 10(6),  and 2.7 x 10(6), respectively. (iii) Component S consists of a unique sequence (Us) bracketed be sequence ca and its inverted repeat a'c', estimated to be of molecular weights 8.3 x 10(6), 3.7 x 10(6), and 3.7 x 10(6), respectively. (iv) The a sequences present at the termini of a complete linear molecule (abUlb'a'a'c'Usca) are arranged in tandem so that the DNA can circularize after limited digestion with arranged in tandem so that the DNA can circularize after limited digestion with lambda 5'-exonuclease. The size of the a sequences was estimated to be 0.7 x 10(6) in molecular weight. (v) At least portions of the a sequences are repeated in an inverted orientation immediately adjacent to or near the a sequence. Thus, BMV DNA mimics herpes simplex virus type 1 DNA with respect to the arrangement but not size of deoxynucleotide sequences. The evolutionary relationship of BMV DNA relative to other herpesvirus DNAs is discussed.", "contents": "Anatomy of bovine mammillitis DNA II. Size and arrangements of the deoxynucleotide sequences. We previously reported that bovine mammillitis virus (BMV) DNA consists of two covalently linked components designated L and S and estimated to be 71.5 x 10(6) and 15.7 x 10(6) in molecular weight, respectively; the components invert relative to each other, giving rise to four equimolar populations differing soley in the relative orientation of the two components. We now report that (i) BMV DNA has a contour length corresponding to a molecular weight of 89 x 10(6). (ii) Component L consists of a unique sequence (Ul) bracketed by sequences ab and its inverted repeat b'a', estimated to be of molecular weights 66.1 x 10(6), 2.7 x 10(6),  and 2.7 x 10(6), respectively. (iii) Component S consists of a unique sequence (Us) bracketed be sequence ca and its inverted repeat a'c', estimated to be of molecular weights 8.3 x 10(6), 3.7 x 10(6), and 3.7 x 10(6), respectively. (iv) The a sequences present at the termini of a complete linear molecule (abUlb'a'a'c'Usca) are arranged in tandem so that the DNA can circularize after limited digestion with arranged in tandem so that the DNA can circularize after limited digestion with lambda 5'-exonuclease. The size of the a sequences was estimated to be 0.7 x 10(6) in molecular weight. (v) At least portions of the a sequences are repeated in an inverted orientation immediately adjacent to or near the a sequence. Thus, BMV DNA mimics herpes simplex virus type 1 DNA with respect to the arrangement but not size of deoxynucleotide sequences. The evolutionary relationship of BMV DNA relative to other herpesvirus DNAs is discussed."}
{"id": "PMID:211254", "title": "Comparison of the genomic organization of Kirsten and Harvey sarcoma viruses.", "content": "Current studies were undertaken to compare the genomes of Kirsten murine sarcoma virus (Ki-MuSV), Harvey murine sarcoma virus (Ha-MuSV), and the replication-defective endogenous rat virus to understand the function of these viral RNAs. Genome organization and sequence homology were studied by fingerprinting large RNase T1-resistant oligonucleotides and by cross-protecting homologous oligonucleotides against RNase A and T1 digestion with complementary DNA prepared from each of the other viral RNA. Ki-MuSV and Ha-MuSV were found to share an extensive series of rat-derived oligonucleotides begining ca. 1 kilobase (kb) from the 3' end and extending to within 1.5 kb of the 5'end of Ki-MuSV RNA. The total map distance covered in ca. 5.5 kb. The eight oligonucleotides covering the 1.5 kb at the 5' end of Ki-MuSV RNA were not found in Ha-MuSV RNA. Five out of these eight oligonucleotides, however, could be designated with certainty to be of rat virus origin. Since Ha-MuSV is 6.5 kb in size and Ki-MuSV is 8 kb in size, the major difference between them is the 1.5 kb from the replication-defective endogenous rat virus sequences at the 5' end of Ki-MuSV not present in Ha-MuSV. Consistent with the difference in the genome structure, these two sarcoma viral RNA'S yielded distinct major translation products in cell-free systems, I.E., A 50,000-dalton polypeptide (P50) from Ki-MuSV and a 22,000-dalton polypeptide (p22) from Ha-MuSV. These polypeptides  may provide the necessary protein makers for identifying in vivo virus-coded proteins.", "contents": "Comparison of the genomic organization of Kirsten and Harvey sarcoma viruses. Current studies were undertaken to compare the genomes of Kirsten murine sarcoma virus (Ki-MuSV), Harvey murine sarcoma virus (Ha-MuSV), and the replication-defective endogenous rat virus to understand the function of these viral RNAs. Genome organization and sequence homology were studied by fingerprinting large RNase T1-resistant oligonucleotides and by cross-protecting homologous oligonucleotides against RNase A and T1 digestion with complementary DNA prepared from each of the other viral RNA. Ki-MuSV and Ha-MuSV were found to share an extensive series of rat-derived oligonucleotides begining ca. 1 kilobase (kb) from the 3' end and extending to within 1.5 kb of the 5'end of Ki-MuSV RNA. The total map distance covered in ca. 5.5 kb. The eight oligonucleotides covering the 1.5 kb at the 5' end of Ki-MuSV RNA were not found in Ha-MuSV RNA. Five out of these eight oligonucleotides, however, could be designated with certainty to be of rat virus origin. Since Ha-MuSV is 6.5 kb in size and Ki-MuSV is 8 kb in size, the major difference between them is the 1.5 kb from the replication-defective endogenous rat virus sequences at the 5' end of Ki-MuSV not present in Ha-MuSV. Consistent with the difference in the genome structure, these two sarcoma viral RNA'S yielded distinct major translation products in cell-free systems, I.E., A 50,000-dalton polypeptide (P50) from Ki-MuSV and a 22,000-dalton polypeptide (p22) from Ha-MuSV. These polypeptides  may provide the necessary protein makers for identifying in vivo virus-coded proteins."}
{"id": "PMID:211255", "title": "Mapping early transcripts of herpes simplex virus type 1 by electron microscopy.", "content": "RNA displacement loop patterns in intact herpes simplex virus DNA and herpes simplex virus DNA restriction fragments indicate that viral RNA associated with polyribosomes early after infection is transcribed from three major areas of the genome. One area of early transcription is in the short segment of the viral DNA and is roughly delineated by the inverted repeat sequences bounding this segment. The other two areas of early mRNA transcription map in the long segment. Each of three major areas of early mRNA transcription can be further resolved into several regions of freqent looping bordered by regions in which RNA displacement loops are rare. These regions range in size from about 1.5 kilobases to about 9 kilobases with a mean size of about 3.5 kilobases. Although the data do not allow precise assignment of individual early gene locations, it is seen, even at the lowest level of resolution, that the early genes are not completely contiguous but are distributed along the length of the herpes simplex type 1 viral genome.", "contents": "Mapping early transcripts of herpes simplex virus type 1 by electron microscopy. RNA displacement loop patterns in intact herpes simplex virus DNA and herpes simplex virus DNA restriction fragments indicate that viral RNA associated with polyribosomes early after infection is transcribed from three major areas of the genome. One area of early transcription is in the short segment of the viral DNA and is roughly delineated by the inverted repeat sequences bounding this segment. The other two areas of early mRNA transcription map in the long segment. Each of three major areas of early mRNA transcription can be further resolved into several regions of freqent looping bordered by regions in which RNA displacement loops are rare. These regions range in size from about 1.5 kilobases to about 9 kilobases with a mean size of about 3.5 kilobases. Although the data do not allow precise assignment of individual early gene locations, it is seen, even at the lowest level of resolution, that the early genes are not completely contiguous but are distributed along the length of the herpes simplex type 1 viral genome."}
{"id": "PMID:211256", "title": "Heterogeneity of Epstein-Barr virus. III. Comparison of a transforming and a nontransforming virus by partial denaturation mapping of their DNAs.", "content": "The DNAs of a transforming and a nontransforming Epstein-Barr virus strain, B95-8 AND P3HR-1, were compared by partial denturation mapping. B95-8 viral DNA showed a homogeneous denaturation pattern. In contrast, P3HR-1 viral DNA was heterogeneous, containing at least two classes of molecules, classified into groups A and B and present in a ratio of about 2:1 to 3:1. No evidence could be obtained that molecules from both groups A and B contain identical sequences present in different orientations as described for herpes simplex viral DNA. The majority of sequences present in B95-8 and in P3HR-1 viral DNA group A could be correlated by assuming that different sequences, about 12,000 base pairs long, were inserted or deleted, respectively, at different position of both viral genomes.", "contents": "Heterogeneity of Epstein-Barr virus. III. Comparison of a transforming and a nontransforming virus by partial denaturation mapping of their DNAs. The DNAs of a transforming and a nontransforming Epstein-Barr virus strain, B95-8 AND P3HR-1, were compared by partial denturation mapping. B95-8 viral DNA showed a homogeneous denaturation pattern. In contrast, P3HR-1 viral DNA was heterogeneous, containing at least two classes of molecules, classified into groups A and B and present in a ratio of about 2:1 to 3:1. No evidence could be obtained that molecules from both groups A and B contain identical sequences present in different orientations as described for herpes simplex viral DNA. The majority of sequences present in B95-8 and in P3HR-1 viral DNA group A could be correlated by assuming that different sequences, about 12,000 base pairs long, were inserted or deleted, respectively, at different position of both viral genomes."}
{"id": "PMID:211257", "title": "New late gene, dar, involved in the replication of bacteriophage T4 DNA. II. Overproduction of DNA binding protein (gene 32 protein) and further characterization.", "content": "We have previously shown that the arrested DNA synthesis of mutant defective in T4 phage gene 59 can be reversed by a mutation in dar. In this paper, we have examined the effect of the dar mutation on the kinetics of gene 32 protein (DNA binding protein) synthesis, DNA packaging, progeny formation, and several other porcesses. Several lines of evidence are presented showing that the regulation of synthesis of gene 32 protein is abnormal in dar 1-infected cells. In these cells, gene 32 protein, an early protein, is also expressed late in the infectious cycle. Our data also indicate that the packaging og DNA into T4 phage heads is delayed in dar mutant-infected cells, and this in turn results in a 6- to 8-min delay in intracellular progeny formation, although the synthesis of late proteins appears to be normal, as shown by gel electrophoresis. We have also studied the phenotypes of the double mutant dar-amC5 (gene 59). The increased sensitivity to hydroxyurea caused by a mutation in the dar gene can be alleviated by a  second mutation in gene 59, but an increased sensitivity to UV irradiation caused by a mutation in gene 59 cannot be alleviated by a second mutation in the dar gene. Therefore, the double mutant still exhibits abnormalities in the repair of UV lesions.", "contents": "New late gene, dar, involved in the replication of bacteriophage T4 DNA. II. Overproduction of DNA binding protein (gene 32 protein) and further characterization. We have previously shown that the arrested DNA synthesis of mutant defective in T4 phage gene 59 can be reversed by a mutation in dar. In this paper, we have examined the effect of the dar mutation on the kinetics of gene 32 protein (DNA binding protein) synthesis, DNA packaging, progeny formation, and several other porcesses. Several lines of evidence are presented showing that the regulation of synthesis of gene 32 protein is abnormal in dar 1-infected cells. In these cells, gene 32 protein, an early protein, is also expressed late in the infectious cycle. Our data also indicate that the packaging og DNA into T4 phage heads is delayed in dar mutant-infected cells, and this in turn results in a 6- to 8-min delay in intracellular progeny formation, although the synthesis of late proteins appears to be normal, as shown by gel electrophoresis. We have also studied the phenotypes of the double mutant dar-amC5 (gene 59). The increased sensitivity to hydroxyurea caused by a mutation in the dar gene can be alleviated by a  second mutation in gene 59, but an increased sensitivity to UV irradiation caused by a mutation in gene 59 cannot be alleviated by a second mutation in the dar gene. Therefore, the double mutant still exhibits abnormalities in the repair of UV lesions."}
{"id": "PMID:211258", "title": "Regulation of murine cytomegalovirus gene expression. I. Transcription during productive infection.", "content": "Murine cytomegalovirus RNA synthesis in productively infected mouse embryo cultures was measured by reassociation kinetics with iodinated viral DNA. The data were analyzed by a computer program and indicated the following: before DNA replication approximately 25% of the genome was transcribed into asymmetric transcripts, of which slightly fewer than half of the sequences were recovered from the cytoplasm. After viral DNA replication, approximately 38% of the genome was transcribed (5% as symmetric transcripts), and again less than half of the sequences appeared in the cytoplasm. Both early and late RNA comprised two abundance classes differing about 8- to 10-fold in concentration. Early RNA was a subset of late RNA. The RNE sequences synthesized in late-infected cells in the presence of cytosine arabinoside or cycloheximide were similar to early RNA. Thus, murine cytomegalovirus displays temporal, quantitative, and post-transcriptional controls over gene expression, but the pattern differs considerably from herpes simplex virus.", "contents": "Regulation of murine cytomegalovirus gene expression. I. Transcription during productive infection. Murine cytomegalovirus RNA synthesis in productively infected mouse embryo cultures was measured by reassociation kinetics with iodinated viral DNA. The data were analyzed by a computer program and indicated the following: before DNA replication approximately 25% of the genome was transcribed into asymmetric transcripts, of which slightly fewer than half of the sequences were recovered from the cytoplasm. After viral DNA replication, approximately 38% of the genome was transcribed (5% as symmetric transcripts), and again less than half of the sequences appeared in the cytoplasm. Both early and late RNA comprised two abundance classes differing about 8- to 10-fold in concentration. Early RNA was a subset of late RNA. The RNE sequences synthesized in late-infected cells in the presence of cytosine arabinoside or cycloheximide were similar to early RNA. Thus, murine cytomegalovirus displays temporal, quantitative, and post-transcriptional controls over gene expression, but the pattern differs considerably from herpes simplex virus."}
{"id": "PMID:211259", "title": "Evidence for a herpes simplex virus-specific factor controlling the transcription of deoxypyrimidine kinase.", "content": "A cistron-specific, enzyme-forming-capacity method was used to study the control of herpes simplex virus (HSV)-specific deoxypyrimidine kinase (dPyK) mRNA synthesis. A virus-specific factor was formed by a primary infecting virus, and this factor effected the transcription of dPyK mRNA of a superinfecting virus in the presence of cycloheximide, suggesting that the factor acted in \"trans\" and was a diffusible one. After the addition of actinomycin D to prevent further transcription and upon removal of cycloheximide, the dPyK mRNA was allowed to express into dPyK activity. A factor from HSV-1 could effect the transcription of dPyK mRNA of both HSV-1 and HSV-2. Amino acid analogs, canavanine or ethionine, inhibited the action of this factor, suggesting that a protein was involved. This protein factor was shown to belong to the alpha (or immediate-early) group of HSV-Specific polypeptides in preductively infected cells.", "contents": "Evidence for a herpes simplex virus-specific factor controlling the transcription of deoxypyrimidine kinase. A cistron-specific, enzyme-forming-capacity method was used to study the control of herpes simplex virus (HSV)-specific deoxypyrimidine kinase (dPyK) mRNA synthesis. A virus-specific factor was formed by a primary infecting virus, and this factor effected the transcription of dPyK mRNA of a superinfecting virus in the presence of cycloheximide, suggesting that the factor acted in \"trans\" and was a diffusible one. After the addition of actinomycin D to prevent further transcription and upon removal of cycloheximide, the dPyK mRNA was allowed to express into dPyK activity. A factor from HSV-1 could effect the transcription of dPyK mRNA of both HSV-1 and HSV-2. Amino acid analogs, canavanine or ethionine, inhibited the action of this factor, suggesting that a protein was involved. This protein factor was shown to belong to the alpha (or immediate-early) group of HSV-Specific polypeptides in preductively infected cells."}
{"id": "PMID:211260", "title": "Interference with simian virus 40 DNA replication by adenovirus type 2 during mixed infection of monkey cells.", "content": "Infection of monkey cells with human adenovirus (Ad) is abortive, but the infection can be enhanced by coinfecting with simian virus 40 (SV40). However, in the coinfected monkey cells, Ad interferes strongly with SV40 DNA biosynthesis. This interference was found to be a reproducible, delicately controlled phenomenon that was proportional to the multiplicity of infection of Ad and dependent on the active expression of the Ad genome. Newly synthesized SV40 DNA was not broken down in cells after delayed superinfection with Ad, and several early events of SV40 infection such as adsorption, penetration, uncoating, induction of cellular DNA synthesis, and enhancement of Ad infection were not markedly influenced by Ad-mediated interference. It is unlikely that interference is simply due to competition between SV40 and Ad for metabolites, enzymes, or replication sites. The interference effect could be partially neutralized by an increase in the multiplicity of coinfecting SV40 or by an increase in the time interval between SV40 infection and Ad coinfection. Interference was shown to be due to the activity of an Ad early gene product. However, the detailed mechanism of this Ad interference is still unclear.", "contents": "Interference with simian virus 40 DNA replication by adenovirus type 2 during mixed infection of monkey cells. Infection of monkey cells with human adenovirus (Ad) is abortive, but the infection can be enhanced by coinfecting with simian virus 40 (SV40). However, in the coinfected monkey cells, Ad interferes strongly with SV40 DNA biosynthesis. This interference was found to be a reproducible, delicately controlled phenomenon that was proportional to the multiplicity of infection of Ad and dependent on the active expression of the Ad genome. Newly synthesized SV40 DNA was not broken down in cells after delayed superinfection with Ad, and several early events of SV40 infection such as adsorption, penetration, uncoating, induction of cellular DNA synthesis, and enhancement of Ad infection were not markedly influenced by Ad-mediated interference. It is unlikely that interference is simply due to competition between SV40 and Ad for metabolites, enzymes, or replication sites. The interference effect could be partially neutralized by an increase in the multiplicity of coinfecting SV40 or by an increase in the time interval between SV40 infection and Ad coinfection. Interference was shown to be due to the activity of an Ad early gene product. However, the detailed mechanism of this Ad interference is still unclear."}
{"id": "PMID:211261", "title": "Transfer of Fv-1 locus-specific resistance to murine N-tropic and B-tropic retroviruses by cytoplasmic RNA.", "content": "A standardized bioassay for transfer of Fv-1 gene-specific resistance to N-tropic and B-tropic murine retroviruses was developed using X plaque reduction in SC-1 (Fv-1-) cells inoculated with virus. Testing of subcellular fractions of restrictive cells showed that the resistance transfer activity was present in the cytoplasmic (microsomal and cytosol) fractions. The activity of the cytoplasmic extract was destroyed by treatment with ribonuclease, but not with deoxyribonuclease or proteases. RNA prepared by phenol-chloroform extraction of mouse tissues, including embryos and livers of weanling mice, transferred Fv-1 locus-specific resistance into DEAE-dextran-treated SC-1 cells. The activity of isolated RNA preparations against virus of the appropriate host-range type has been demonstrated to correspond to the Fv-1 genotypes of the cell sources. The specific transfer of resistance with cellular RNA was effective within a 5- to 6-h period from 2 h before to 4 to 5 after virus infection. Sucrose gradient centrifugation of the RNA showed that the activity sedimented as a broad peak, with an apparent maximum in the 22S region. Affinity chromatography of whole-cell RNA on polyuridylic acid-Sepharose tended to separate more activity into the polyadenylic acid RNA fraction than the non-polyadenylic acid RNA fraction. Except for the reciprocal inhibitory activity for the two host-range virus types, the RNAs of Fv-1n and Fv-1b specificities showed similar properties in all aspects studied.", "contents": "Transfer of Fv-1 locus-specific resistance to murine N-tropic and B-tropic retroviruses by cytoplasmic RNA. A standardized bioassay for transfer of Fv-1 gene-specific resistance to N-tropic and B-tropic murine retroviruses was developed using X plaque reduction in SC-1 (Fv-1-) cells inoculated with virus. Testing of subcellular fractions of restrictive cells showed that the resistance transfer activity was present in the cytoplasmic (microsomal and cytosol) fractions. The activity of the cytoplasmic extract was destroyed by treatment with ribonuclease, but not with deoxyribonuclease or proteases. RNA prepared by phenol-chloroform extraction of mouse tissues, including embryos and livers of weanling mice, transferred Fv-1 locus-specific resistance into DEAE-dextran-treated SC-1 cells. The activity of isolated RNA preparations against virus of the appropriate host-range type has been demonstrated to correspond to the Fv-1 genotypes of the cell sources. The specific transfer of resistance with cellular RNA was effective within a 5- to 6-h period from 2 h before to 4 to 5 after virus infection. Sucrose gradient centrifugation of the RNA showed that the activity sedimented as a broad peak, with an apparent maximum in the 22S region. Affinity chromatography of whole-cell RNA on polyuridylic acid-Sepharose tended to separate more activity into the polyadenylic acid RNA fraction than the non-polyadenylic acid RNA fraction. Except for the reciprocal inhibitory activity for the two host-range virus types, the RNAs of Fv-1n and Fv-1b specificities showed similar properties in all aspects studied."}
{"id": "PMID:211262", "title": "Presence of free viral DNA in simian virus 40-transformed nonproducer cells.", "content": "Extracts from several simian virus 40 (SV40)-transformed nonproducer cells were prepared by the hot-phenol procedure normally used to extract cellular RNA. These extracts contained SV40 infectious units. Part of the infectious units were identified as SV40 form I DNA molecules. The results of reconstruction experiments suggest that SV40 form I DNA is extractable by the hot-phenol procedure because of its fast renaturation rate. The significance of the presence of free viral DNA in nonproducer transformed cells is discussed.", "contents": "Presence of free viral DNA in simian virus 40-transformed nonproducer cells. Extracts from several simian virus 40 (SV40)-transformed nonproducer cells were prepared by the hot-phenol procedure normally used to extract cellular RNA. These extracts contained SV40 infectious units. Part of the infectious units were identified as SV40 form I DNA molecules. The results of reconstruction experiments suggest that SV40 form I DNA is extractable by the hot-phenol procedure because of its fast renaturation rate. The significance of the presence of free viral DNA in nonproducer transformed cells is discussed."}
{"id": "PMID:211263", "title": "Interaction of vesicular stomatitis virus with lipid vesicles: depletion of cholesterol and effect on virion membrane fluidity and infectivity.", "content": "Interaction with excess unilamellar phosphatidylcholine (PC) vesicles resulted in depletion of as much as 90% of the cholesterol from the membrane of intact vesicular stomatitis (VS) virus. The cholesterol depletion was not significantly influenced by the proteolytic removal of virion glycoprotein spikes, but it was temperature dependent. Cholesterol depletion caused substantial reduction in anisotropy of the VS virion membrane as measured by fluorescence depolarization of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene; residual adsorbed vesicles represent a significant factor in this apparent increase in virion membrane fluidity. Interaction with PC vesicles resulted in a substantial loss of VS viral infectivity as measured by plating efficiency on L-cell monolayers. Reduction in infectivity appeared to be related to temperature-dependent depletion of virion cholesterol by PC vesicles. Interaction of VS virions with cholesterol-containing PC vesicles resulted in significantly less decline in infectivity, but attempts to restore cholesterol and infectivity to depleted VS virions were unsuccessful. Depletion of virion cholesterol apparently results through collision with PC vesicles rather than movement of cholesterol monomers or micelles through the aqueous phase, because PC vesicle-virion interaction in the presence of cholesterol oxidase did not result in substantial oxidation of translocated cholesterol.", "contents": "Interaction of vesicular stomatitis virus with lipid vesicles: depletion of cholesterol and effect on virion membrane fluidity and infectivity. Interaction with excess unilamellar phosphatidylcholine (PC) vesicles resulted in depletion of as much as 90% of the cholesterol from the membrane of intact vesicular stomatitis (VS) virus. The cholesterol depletion was not significantly influenced by the proteolytic removal of virion glycoprotein spikes, but it was temperature dependent. Cholesterol depletion caused substantial reduction in anisotropy of the VS virion membrane as measured by fluorescence depolarization of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene; residual adsorbed vesicles represent a significant factor in this apparent increase in virion membrane fluidity. Interaction with PC vesicles resulted in a substantial loss of VS viral infectivity as measured by plating efficiency on L-cell monolayers. Reduction in infectivity appeared to be related to temperature-dependent depletion of virion cholesterol by PC vesicles. Interaction of VS virions with cholesterol-containing PC vesicles resulted in significantly less decline in infectivity, but attempts to restore cholesterol and infectivity to depleted VS virions were unsuccessful. Depletion of virion cholesterol apparently results through collision with PC vesicles rather than movement of cholesterol monomers or micelles through the aqueous phase, because PC vesicle-virion interaction in the presence of cholesterol oxidase did not result in substantial oxidation of translocated cholesterol."}
{"id": "PMID:211264", "title": "Shedding of the glycoprotein from vesicular stomatitis virus-infected cells.", "content": "In a culture of Chinese hamster ovary cells infected with vesicular stomatitis virus, there is specific shedding of viral antigens into the medium. This shedding appears to be unrelated to progeny formation or to cell lysis. Although all five of the virus-specific proteins are detected in the extracellular soluble fraction, the major antigen is the Gs protein. This protein has a molecular weight of 54,000. Indirect analysis of the content of sialic acid as well as peptide analysis of the Gs and G proteins of vesicular stomatitis virus suggest that the Gs protein is derived from the G protein by proteolysis. Both proteins are hydrophobic when analyzed by charge-shift electrophoresis. The presence of phenylmethylsulfonyl fluoride in the culture medium or the removal of serum from the culture medium partially reduces the shedding of Gs protein. Increased shedding of the Gs protein is seen when there is an unstable M or matrix protein synthesized by a temperature-sensitive mutant, tsG31. These results indicate that the G protein is cleaved at the cell surface, thus releasing Gs protein into the medium. Furthermore, the stability of G protein at the cell surface appears to be dependent on its association with the M protein.", "contents": "Shedding of the glycoprotein from vesicular stomatitis virus-infected cells. In a culture of Chinese hamster ovary cells infected with vesicular stomatitis virus, there is specific shedding of viral antigens into the medium. This shedding appears to be unrelated to progeny formation or to cell lysis. Although all five of the virus-specific proteins are detected in the extracellular soluble fraction, the major antigen is the Gs protein. This protein has a molecular weight of 54,000. Indirect analysis of the content of sialic acid as well as peptide analysis of the Gs and G proteins of vesicular stomatitis virus suggest that the Gs protein is derived from the G protein by proteolysis. Both proteins are hydrophobic when analyzed by charge-shift electrophoresis. The presence of phenylmethylsulfonyl fluoride in the culture medium or the removal of serum from the culture medium partially reduces the shedding of Gs protein. Increased shedding of the Gs protein is seen when there is an unstable M or matrix protein synthesized by a temperature-sensitive mutant, tsG31. These results indicate that the G protein is cleaved at the cell surface, thus releasing Gs protein into the medium. Furthermore, the stability of G protein at the cell surface appears to be dependent on its association with the M protein."}
{"id": "PMID:211265", "title": "Identification of a protein linked to nascent poliovirus RNA and to the polyuridylic acid of negative-strand RNA.", "content": "A protein similar to that previously demonstrated on poliovirus RNA and replicative intermediate RNA (VPg) was found on all sizes of nascent viral RNA molecules and on the polyuridylic acid isolated from negative-strand RNA. 32P-labeled nascent chains were released from their template RNA and fractionated by exclusion chromatography on agarose. Fingerprint analysis using two-dimensional polyacrylamide gels of RNase T1 oligonucleotides derived from nascent chains of different lengths showed that a size fractionation of nascent chains was achieved. VPg was recovered from nascent chains varying in length from 7,500 nucleotides (full-sized RNA) to about 500 nucleotides. No other type of 5' terminus could be demonstrated on nascent RNA, and the yield of VPg was consistent with one molecule of the protein on each nascent chain. These results are consistent with the concept that the protein is added to the 5' end of the growing RNA chains at a very early stage, possibly as a primer of RNA synthesis. Analysis of the polyuridylic acid tract isolated from the replicative intermediate and double-stranded RNAs indicated that a protein of the same size as that found on the nascent chains and virion RNA is also linked to the negative-strand RNAs. It is likely that a similar mechanism is responsible for initiation of synthesis of both plus- and minus-strand RNAs.", "contents": "Identification of a protein linked to nascent poliovirus RNA and to the polyuridylic acid of negative-strand RNA. A protein similar to that previously demonstrated on poliovirus RNA and replicative intermediate RNA (VPg) was found on all sizes of nascent viral RNA molecules and on the polyuridylic acid isolated from negative-strand RNA. 32P-labeled nascent chains were released from their template RNA and fractionated by exclusion chromatography on agarose. Fingerprint analysis using two-dimensional polyacrylamide gels of RNase T1 oligonucleotides derived from nascent chains of different lengths showed that a size fractionation of nascent chains was achieved. VPg was recovered from nascent chains varying in length from 7,500 nucleotides (full-sized RNA) to about 500 nucleotides. No other type of 5' terminus could be demonstrated on nascent RNA, and the yield of VPg was consistent with one molecule of the protein on each nascent chain. These results are consistent with the concept that the protein is added to the 5' end of the growing RNA chains at a very early stage, possibly as a primer of RNA synthesis. Analysis of the polyuridylic acid tract isolated from the replicative intermediate and double-stranded RNAs indicated that a protein of the same size as that found on the nascent chains and virion RNA is also linked to the negative-strand RNAs. It is likely that a similar mechanism is responsible for initiation of synthesis of both plus- and minus-strand RNAs."}
{"id": "PMID:211266", "title": "Structure of the joint region and the termini of the DNA of herpes simplex virus type 1.", "content": "Analysis of restriction endonuclease cleavage sites within the inverted, repeated sequences in the joint region of the DNA of herpes simplex virus type 1 strain KOS revealed the presence of two types of sequence heterogeneity. The first was an insertion of 280 base pairs or multiples of 280 base pairs which was found in approximately half of all DNA molecules from every plaque-purified stock of virus. These insertions seemed to be tandem duplications of sequences which were present at the joint and correspond closely to the inverted terminal redunancy. The second type of heterogeneity was due to variable insertions and deletions which were present in some, but not all, plaque-purified virus stocks. Comparison of restriction fragments from the joint region with fragments from the termini indicated that in the simplest observed molecules of herpes simplex virus type 1 DNA, only one copy of the inverted terminal redundancy was present at the joint. A map of restriction endonuclease cleavage sites in the joint region is presented.", "contents": "Structure of the joint region and the termini of the DNA of herpes simplex virus type 1. Analysis of restriction endonuclease cleavage sites within the inverted, repeated sequences in the joint region of the DNA of herpes simplex virus type 1 strain KOS revealed the presence of two types of sequence heterogeneity. The first was an insertion of 280 base pairs or multiples of 280 base pairs which was found in approximately half of all DNA molecules from every plaque-purified stock of virus. These insertions seemed to be tandem duplications of sequences which were present at the joint and correspond closely to the inverted terminal redunancy. The second type of heterogeneity was due to variable insertions and deletions which were present in some, but not all, plaque-purified virus stocks. Comparison of restriction fragments from the joint region with fragments from the termini indicated that in the simplest observed molecules of herpes simplex virus type 1 DNA, only one copy of the inverted terminal redundancy was present at the joint. A map of restriction endonuclease cleavage sites in the joint region is presented."}
{"id": "PMID:211267", "title": "DNA of Epstein-Barr virus. III. Identification of restriction enzyme fragments that contain DNA sequences which differ among strains of Epstein-Barr virus.", "content": "Previous kinetic and absorption hybridization experiments had demonstrated that the DNA of the B95-8 strain of Epstein-Barr virus was missing approximately 10% of the DNA sequences present in the DNA of the HR-1 strain (R.F. Pritchett, S.D. Hayward, and E. Kieff, J. Virol. 15:556-569, 1975; B. Sugder, W.C. Summers, and G. Klein, J. Virol. 18:765-775, 1976). The HR-1 strain differs from other laboratory strains, including the B95-8 and W91 strains, and from virus present in throat washings from patients with infectious mononucleosis in its inability to transform lymphocytes into lymphoblasts capable of long-term growth in culture (P. Gerber, Lancet i:1001, 1973; J. Menezes, W. Leibold, and G. Klein, Exp. Cell. Res. 92:478-484, 1975; G. Miller, D. Coope, J. Niederman, and J. Pagano, J. Virol. 18:1071-1080, 1976; G. Miller, J. Robinson, L. Heston, and M. Lipman, Proc. Natl. Acad. Sci. U.S.A. 71:4006-4010, 1974). In the experiments reported here, the restriction enzyme fragments of Epstein-Barr virus DNA which contain sequences which differ among the HR-1, B95-8, and W91 strains have been identified. The DNA of the HR-1, B95-8, and W91 strains each differed in complexity. The sequences previously shown to be missing in the B95-8 strain were contained in the EcoRI-C and -D and Hsu I-E and -N fragments of the HR-1 strain and in the EcoRI-C and Hsu I-D and -E fragments of the W91 strain. The HR-1 strain was missing DNA contained in EcoRI fragments A and J through K and Hsu I fragment B of the B95-8 strain and in the EcoRI-A and Hsu I-B fragments of the W91 strain. The relationship of these data to the linkage map of restriction enzyme fragments of the DNA of the B95-8 and W91 strains (E. Kieff, N. Raab-Traub, D. Given, W. King, A.T. Powell, R. Pritchett, and T. Dambaugh, In F. Rapp and G. de-The, ed., Oncogenesis and Herpesviruses III, in press; D. Given and E. Kieff, submitted for publication) and the possible significance of the data are discussed.", "contents": "DNA of Epstein-Barr virus. III. Identification of restriction enzyme fragments that contain DNA sequences which differ among strains of Epstein-Barr virus. Previous kinetic and absorption hybridization experiments had demonstrated that the DNA of the B95-8 strain of Epstein-Barr virus was missing approximately 10% of the DNA sequences present in the DNA of the HR-1 strain (R.F. Pritchett, S.D. Hayward, and E. Kieff, J. Virol. 15:556-569, 1975; B. Sugder, W.C. Summers, and G. Klein, J. Virol. 18:765-775, 1976). The HR-1 strain differs from other laboratory strains, including the B95-8 and W91 strains, and from virus present in throat washings from patients with infectious mononucleosis in its inability to transform lymphocytes into lymphoblasts capable of long-term growth in culture (P. Gerber, Lancet i:1001, 1973; J. Menezes, W. Leibold, and G. Klein, Exp. Cell. Res. 92:478-484, 1975; G. Miller, D. Coope, J. Niederman, and J. Pagano, J. Virol. 18:1071-1080, 1976; G. Miller, J. Robinson, L. Heston, and M. Lipman, Proc. Natl. Acad. Sci. U.S.A. 71:4006-4010, 1974). In the experiments reported here, the restriction enzyme fragments of Epstein-Barr virus DNA which contain sequences which differ among the HR-1, B95-8, and W91 strains have been identified. The DNA of the HR-1, B95-8, and W91 strains each differed in complexity. The sequences previously shown to be missing in the B95-8 strain were contained in the EcoRI-C and -D and Hsu I-E and -N fragments of the HR-1 strain and in the EcoRI-C and Hsu I-D and -E fragments of the W91 strain. The HR-1 strain was missing DNA contained in EcoRI fragments A and J through K and Hsu I fragment B of the B95-8 strain and in the EcoRI-A and Hsu I-B fragments of the W91 strain. The relationship of these data to the linkage map of restriction enzyme fragments of the DNA of the B95-8 and W91 strains (E. Kieff, N. Raab-Traub, D. Given, W. King, A.T. Powell, R. Pritchett, and T. Dambaugh, In F. Rapp and G. de-The, ed., Oncogenesis and Herpesviruses III, in press; D. Given and E. Kieff, submitted for publication) and the possible significance of the data are discussed."}
{"id": "PMID:211268", "title": "Polyoma virus has three late mRNA's: one for each virion protein.", "content": "Polyoma virus mRNA, isolated from the cytoplasm of 3T6 cells late after infection and purified by hybridization to HpaII fragment 3 of polyoma virus DNA, was separated on 50% formamide-containing sucrose density gradients, and the fractionated RNA was recovered and translated in vitro. Analysis of the cell-free products showed that the minor virion protein VP3 was synthesized from an mRNA sedimenting at approximately 18S betweeen the 19S VP2 mRN and the 16S VP1 mRNA. Other experiments showed that the VP2 and VP3 can be labeled with formyl methionine from initiator tRNA. We conclude that there are three late polyoma virus mRNA's, each directing the synthesis of only one viral capsid protein.", "contents": "Polyoma virus has three late mRNA's: one for each virion protein. Polyoma virus mRNA, isolated from the cytoplasm of 3T6 cells late after infection and purified by hybridization to HpaII fragment 3 of polyoma virus DNA, was separated on 50% formamide-containing sucrose density gradients, and the fractionated RNA was recovered and translated in vitro. Analysis of the cell-free products showed that the minor virion protein VP3 was synthesized from an mRNA sedimenting at approximately 18S betweeen the 19S VP2 mRN and the 16S VP1 mRNA. Other experiments showed that the VP2 and VP3 can be labeled with formyl methionine from initiator tRNA. We conclude that there are three late polyoma virus mRNA's, each directing the synthesis of only one viral capsid protein."}
{"id": "PMID:211269", "title": "Chromatographic separation of the polyoma virus proteins and renaturation of the isolated VP1 major capsid protein.", "content": "Treatment of purified polyoma virions with 6 M guanidine-hydrochloride and 0.01 M beta-mercaptoethanol resulted in the immediate loss of both hemagglutinating and plaque-forming ability. Gel filtration through Sepharose CL-6B beads allowed separation of the dimer, VP1, VP2, VP3, and histone proteins VP4-7 in highly purified form. Renaturation of the purified VP1 protein resulted in the formation of subunits that were morphologically, biophysically, and immunologically similar to native virion capsomeres.", "contents": "Chromatographic separation of the polyoma virus proteins and renaturation of the isolated VP1 major capsid protein. Treatment of purified polyoma virions with 6 M guanidine-hydrochloride and 0.01 M beta-mercaptoethanol resulted in the immediate loss of both hemagglutinating and plaque-forming ability. Gel filtration through Sepharose CL-6B beads allowed separation of the dimer, VP1, VP2, VP3, and histone proteins VP4-7 in highly purified form. Renaturation of the purified VP1 protein resulted in the formation of subunits that were morphologically, biophysically, and immunologically similar to native virion capsomeres."}
{"id": "PMID:211270", "title": "Proteolysis of noncapsid protein 2 of type 3 poliovirus at the restrictive temperature: breakdown of noncapsid protein 2 correlates with loss of RNA synthesis.", "content": "Inhibition of RNA synthesis of the LH strain of type 3 poliovirus at the restrictive temperature occurs concurrently with the breakdown of noncapsid virus-specific peptide 2. This finding, along with other reported data (B.D. Korant, In Proteases and Biological Control, p. 621-644, 1975), suggests that noncapsid virus-specific peptide 2 is a component of the viral replicase.", "contents": "Proteolysis of noncapsid protein 2 of type 3 poliovirus at the restrictive temperature: breakdown of noncapsid protein 2 correlates with loss of RNA synthesis. Inhibition of RNA synthesis of the LH strain of type 3 poliovirus at the restrictive temperature occurs concurrently with the breakdown of noncapsid virus-specific peptide 2. This finding, along with other reported data (B.D. Korant, In Proteases and Biological Control, p. 621-644, 1975), suggests that noncapsid virus-specific peptide 2 is a component of the viral replicase."}
{"id": "PMID:211271", "title": "Skin papillomas in an impala (Aepyceros melampus) and a giraffe (Giraffa camelopardalis).", "content": "Viral particles, typical of the papovavirus family, were demonstrated by electronmicroscopy in small papillomas found on the feet of an impala (Aepyceros melampus) and on the face of a giraffe (Giraffa camelopardalis) in Kenya. Histologically the tissues proved to be typical papillomas. The viral particles measured 38 nm and 40 nm in diameter in all tissue sections from the impala and giraffe respectively.", "contents": "Skin papillomas in an impala (Aepyceros melampus) and a giraffe (Giraffa camelopardalis). Viral particles, typical of the papovavirus family, were demonstrated by electronmicroscopy in small papillomas found on the feet of an impala (Aepyceros melampus) and on the face of a giraffe (Giraffa camelopardalis) in Kenya. Histologically the tissues proved to be typical papillomas. The viral particles measured 38 nm and 40 nm in diameter in all tissue sections from the impala and giraffe respectively."}
{"id": "PMID:211272", "title": "Natural pox infection in a common murre (Uria aalge).", "content": "Natural pox infection occurred in a free-living, immature common murre (Uria aalge) in northern California. Cutaneous and diphtheritic lesions were present. Death of the bird was attributed to respiratory insufficiency and starvation resulting from impairment of breathing and feeding, respectively.", "contents": "Natural pox infection in a common murre (Uria aalge). Natural pox infection occurred in a free-living, immature common murre (Uria aalge) in northern California. Cutaneous and diphtheritic lesions were present. Death of the bird was attributed to respiratory insufficiency and starvation resulting from impairment of breathing and feeding, respectively."}
{"id": "PMID:211273", "title": "Rotavirus (reovirus-like) infection of neonatal ruminants in a zoo nursery.", "content": "An outbreak of a pneumoenteric disease occurred in neonates in a zoo nursery. Four of seven affected animals died. Rotaviruses were observed in the feces of an affected 4-day old impala (Aepyceros melampus), a Thomson's gazelle (Gazella thomsonii) and an addax (Addax nasomaculatus). Encapsulated Escherichia coli also were isolated from the feces. The recovered rotaviruses was antigenically related to bovine rotavirus. A bovine rotavirus vaccine was given orally and no adverse effects were noted.", "contents": "Rotavirus (reovirus-like) infection of neonatal ruminants in a zoo nursery. An outbreak of a pneumoenteric disease occurred in neonates in a zoo nursery. Four of seven affected animals died. Rotaviruses were observed in the feces of an affected 4-day old impala (Aepyceros melampus), a Thomson's gazelle (Gazella thomsonii) and an addax (Addax nasomaculatus). Encapsulated Escherichia coli also were isolated from the feces. The recovered rotaviruses was antigenically related to bovine rotavirus. A bovine rotavirus vaccine was given orally and no adverse effects were noted."}
{"id": "PMID:211274", "title": "Neutralising antibodies to parainfluenza 3 virus in African wildlife, with special reference to the Cape buffalo (Syncerus caffer).", "content": "As part of a study to assess the prevalence of common viral agents in African wildlife, nearly 3,300 sera from 44 different wild species, from eight African countries, have been examined for neutralising antibodies to parainfluenza 3 (PI3) virus. Antibody was demonstrated in 20 of the 44 species examined, including seven species not previously reported as sero-positive. Sera were collected between 1963 and 1977 and results indicated that infection has been widespread for a considerable time. The high prevalence of antibody, and the range of titres, to PI3 virus found in free-living populations of buffalo suggest that this species is particularly important as a reservoir of infection in the wild.", "contents": "Neutralising antibodies to parainfluenza 3 virus in African wildlife, with special reference to the Cape buffalo (Syncerus caffer). As part of a study to assess the prevalence of common viral agents in African wildlife, nearly 3,300 sera from 44 different wild species, from eight African countries, have been examined for neutralising antibodies to parainfluenza 3 (PI3) virus. Antibody was demonstrated in 20 of the 44 species examined, including seven species not previously reported as sero-positive. Sera were collected between 1963 and 1977 and results indicated that infection has been widespread for a considerable time. The high prevalence of antibody, and the range of titres, to PI3 virus found in free-living populations of buffalo suggest that this species is particularly important as a reservoir of infection in the wild."}
{"id": "PMID:211275", "title": "Parainfluenza virus type 3: isolation from CSF of a patient with Guillain-Barr\u00e9 syndrome.", "content": "We report the isolation of parainfluenza virus type 3 from the CSF of a 19-year-old man with Guillain-Barr\u00e9 syndrome. Although parainfluenza viruses are usually associated with respiratory tract illnesses, some strains show a neurotropism not previously appreciated. Thus, parainfluenza viruses may be responsible for a portion of cases of Guillain-Barr\u00e9 syndrome.", "contents": "Parainfluenza virus type 3: isolation from CSF of a patient with Guillain-Barr\u00e9 syndrome. We report the isolation of parainfluenza virus type 3 from the CSF of a 19-year-old man with Guillain-Barr\u00e9 syndrome. Although parainfluenza viruses are usually associated with respiratory tract illnesses, some strains show a neurotropism not previously appreciated. Thus, parainfluenza viruses may be responsible for a portion of cases of Guillain-Barr\u00e9 syndrome."}
{"id": "PMID:211305", "title": "Effects of several monoamine-related compounds on the reserpine-induced spikes recorded from the medial nucleus trapezoides in rabbits.", "content": "Effects of several monoamine-related compounds on the reserpine-induced spikes recoreded from the medial nucleus Trapezoides (reserpine-induced Tr spikes) in rabbits were investigated. 5HTP (30--50 mg/kg, i.p.) showed marked suppression of reserpine-induced Tr spikes. Parachlorophenylalanine (PCPA) alone induced spikes similar to reserpine-induced Tr spikes after repeated doses (250 mg/kg twice daily for 3 successive days). A marked enhancement of the generation of reserpine-induced Tr spikes was elicited, when reserpine was given to rabbits pretreated with PCPA. L-DOPA (30--50 mg/kg, i.p.) showed a slight but significant suppressive action 20 to 40 min after injection. alpha-methyl-p-tyrosine (alpha-MT) (200 mg/kg, i.p.) produced no significant change within 6 hr, but did show a marked facilitatory effect on the generation of the spikes when reserpine was given to rabbits pretreated with alpha-MT. alpha-methyl-metatyrosine (alpha-MMT) (100 mg/kg, i.v.) caused a long-lasting, marked suppression. These findings suggest that both catecholamines and 5HT have a suppressive action on the generation of reserpine-induced Tr spikes.", "contents": "Effects of several monoamine-related compounds on the reserpine-induced spikes recorded from the medial nucleus trapezoides in rabbits. Effects of several monoamine-related compounds on the reserpine-induced spikes recoreded from the medial nucleus Trapezoides (reserpine-induced Tr spikes) in rabbits were investigated. 5HTP (30--50 mg/kg, i.p.) showed marked suppression of reserpine-induced Tr spikes. Parachlorophenylalanine (PCPA) alone induced spikes similar to reserpine-induced Tr spikes after repeated doses (250 mg/kg twice daily for 3 successive days). A marked enhancement of the generation of reserpine-induced Tr spikes was elicited, when reserpine was given to rabbits pretreated with PCPA. L-DOPA (30--50 mg/kg, i.p.) showed a slight but significant suppressive action 20 to 40 min after injection. alpha-methyl-p-tyrosine (alpha-MT) (200 mg/kg, i.p.) produced no significant change within 6 hr, but did show a marked facilitatory effect on the generation of the spikes when reserpine was given to rabbits pretreated with alpha-MT. alpha-methyl-metatyrosine (alpha-MMT) (100 mg/kg, i.v.) caused a long-lasting, marked suppression. These findings suggest that both catecholamines and 5HT have a suppressive action on the generation of reserpine-induced Tr spikes."}
{"id": "PMID:211311", "title": "[Deposits of immunoglobulins in the cells of chronic lymphocytic leukemia (author's transl)].", "content": "Cristalloid inclusions were demonstrated in the perinuclear space and the ergastoplasm of cells of chronic lymphocytic leukemia. These inclusions and the immunoglobulins of the cell membrane consisted of IgG. The leukemic cells were able to synthesize, but not to secrete, monoclonal immunoglobulins.", "contents": "[Deposits of immunoglobulins in the cells of chronic lymphocytic leukemia (author's transl)]. Cristalloid inclusions were demonstrated in the perinuclear space and the ergastoplasm of cells of chronic lymphocytic leukemia. These inclusions and the immunoglobulins of the cell membrane consisted of IgG. The leukemic cells were able to synthesize, but not to secrete, monoclonal immunoglobulins."}
{"id": "PMID:211312", "title": "[Virilism due to an adrenal medullary tumor with ectopic ACTH syndrome (author's transl)].", "content": "The case of a 14-year-old girl with hirsutism and virilism due to the secretion of ectopic ACTH by an adrenal medullary tumor is described. At the age of 5 years changes in appearance had begun with masculinization. The effect of ACTH-like material, measured by radioimmunoassay in plasma and in tumor tissue, was compensated partially by the hypothalamo-pituitary-adrenal feedback mechanism. Increased concentrations of dehydroepiandrosterone, estrone and testosterone in plasma and of 17-ketosteroids and free cortisol in urine originated in the adrenals. After operation of the tumor menarche began spontaneously, hirsutism disappeared and testosterone plasma concentrations returned to normal. An adrenogenital syndrome was excluded.", "contents": "[Virilism due to an adrenal medullary tumor with ectopic ACTH syndrome (author's transl)]. The case of a 14-year-old girl with hirsutism and virilism due to the secretion of ectopic ACTH by an adrenal medullary tumor is described. At the age of 5 years changes in appearance had begun with masculinization. The effect of ACTH-like material, measured by radioimmunoassay in plasma and in tumor tissue, was compensated partially by the hypothalamo-pituitary-adrenal feedback mechanism. Increased concentrations of dehydroepiandrosterone, estrone and testosterone in plasma and of 17-ketosteroids and free cortisol in urine originated in the adrenals. After operation of the tumor menarche began spontaneously, hirsutism disappeared and testosterone plasma concentrations returned to normal. An adrenogenital syndrome was excluded."}
{"id": "PMID:211313", "title": "Control of plasma aldosterone in a patient with Conn's syndrome before and during spironolactone medication.", "content": "In a patient suffering from Conn's syndrome analysis of short-time fluctuations of plasma aldosterone, plasma cortisol and plasma renin activity were performed before and after a 9-months therapy period with spironolactone. Under the former conditions aldosterone was secreted episodically and a highly significant correlation was found between plasma aldosterone and plasma cortisol (r=0.817, p is less than 0.001) while plasma renin activity was undetectable (is less than 0.16 ng/ml/3hr). Following a 9-month therapy with spironolactone episodic secretion of aldosterone and the significant correlation between aldosterone and cortisol persisted (r=0.819, p less than 0.001) in the presence of an abnormally high plasma renin activity. First when the secretion of ACTH was suppressed by dexamethasone a weak correlation was found between renin activity and aldosterone (r=0.517, p is less than 0.05). Our results show that both before and after a 9-months therapy with spironolactone episodic aldosterone release of an aldosterone producing adrenal adenoma was mediated through ACTH and that endogeneous angiotensin II had no or only little influence.", "contents": "Control of plasma aldosterone in a patient with Conn's syndrome before and during spironolactone medication. In a patient suffering from Conn's syndrome analysis of short-time fluctuations of plasma aldosterone, plasma cortisol and plasma renin activity were performed before and after a 9-months therapy period with spironolactone. Under the former conditions aldosterone was secreted episodically and a highly significant correlation was found between plasma aldosterone and plasma cortisol (r=0.817, p is less than 0.001) while plasma renin activity was undetectable (is less than 0.16 ng/ml/3hr). Following a 9-month therapy with spironolactone episodic secretion of aldosterone and the significant correlation between aldosterone and cortisol persisted (r=0.819, p less than 0.001) in the presence of an abnormally high plasma renin activity. First when the secretion of ACTH was suppressed by dexamethasone a weak correlation was found between renin activity and aldosterone (r=0.517, p is less than 0.05). Our results show that both before and after a 9-months therapy with spironolactone episodic aldosterone release of an aldosterone producing adrenal adenoma was mediated through ACTH and that endogeneous angiotensin II had no or only little influence."}
{"id": "PMID:211314", "title": "[The enzymatic linkage of fibrinogenesis and fibrinolysis (author's transl)].", "content": "The coagulation cascade can be triggered by an extrinsic or intrinsic signal. The response is a highly complex activation sequence of several serine proteases. This physiological event of hemostasis comprises the activation of the kinin system as well as other plasma constituents. As an expression of the dynamic balance between fibrinogenesis and fibrinolysis plasminogen is activated either by proteases deriving from the blood clotting cascade or by its linkage to the kallikrein kinin system. Inhibitors of the fibrinolytic events have to be directed specifically against serine proteases or they may be used to interact with the substrate fibrin thus its degradation is delayed.", "contents": "[The enzymatic linkage of fibrinogenesis and fibrinolysis (author's transl)]. The coagulation cascade can be triggered by an extrinsic or intrinsic signal. The response is a highly complex activation sequence of several serine proteases. This physiological event of hemostasis comprises the activation of the kinin system as well as other plasma constituents. As an expression of the dynamic balance between fibrinogenesis and fibrinolysis plasminogen is activated either by proteases deriving from the blood clotting cascade or by its linkage to the kallikrein kinin system. Inhibitors of the fibrinolytic events have to be directed specifically against serine proteases or they may be used to interact with the substrate fibrin thus its degradation is delayed."}
{"id": "PMID:211315", "title": "[Relationship between the plasma concentration of the high density lipoproteins (HDL) and the intravenous fat tolerance in normo-and hypertriglyceridaemics].", "content": "The relationship between the plasma concentration of high-density-lipoprotein(HDL)-cholesterol, very-low-density-lipoprotein(VLDL)-triglycerides, and low-density-lipoprotein(LDL)-cholesterol and the fractional removal rate (K2) of an intravenously administered fat emulsion (Intralipid) was investigated in 13 normo- and 34 hypertriglyceridaemics. A highly significant correlation (p less than 0,001) between the plasma concentration of HDL-cholesterol and the fractional removal rate of exogenous triglycerides was found for both groups. No significant relationship existed between the concentration of VLDL-triglycerides and of LDL-cholesterol and the removal rate of exogenous triglycerides. These observations suggest a major role of HDL in the removal of plasma triglycerides.", "contents": "[Relationship between the plasma concentration of the high density lipoproteins (HDL) and the intravenous fat tolerance in normo-and hypertriglyceridaemics]. The relationship between the plasma concentration of high-density-lipoprotein(HDL)-cholesterol, very-low-density-lipoprotein(VLDL)-triglycerides, and low-density-lipoprotein(LDL)-cholesterol and the fractional removal rate (K2) of an intravenously administered fat emulsion (Intralipid) was investigated in 13 normo- and 34 hypertriglyceridaemics. A highly significant correlation (p less than 0,001) between the plasma concentration of HDL-cholesterol and the fractional removal rate of exogenous triglycerides was found for both groups. No significant relationship existed between the concentration of VLDL-triglycerides and of LDL-cholesterol and the removal rate of exogenous triglycerides. These observations suggest a major role of HDL in the removal of plasma triglycerides."}
{"id": "PMID:211317", "title": "[Hodgkin's disease: effect of spenectomy on the immune status (author's transl)].", "content": "In 22 untreated Hodgkin's patients the following parameters were studied before and after splenectomy: the total WBC, lymphocytes, B- and T-cells and mitogenic stimulation of peripheral lymphocytes using autologous and control serum. The results were correlated to patient groups with favourable and unfavourable prognosis according to pathological stage, histology, spleen involvement and constitutional symptoms. 1. All Patients. Significant increase of the absolute number of peripheral lymphocytes and B-cells. Significant increase of the spontanous DNA synthesis in the presence of AB-control serum, but no change after mitogenic stimulation of peripheral lymphocytes. No change in the number of peripheral T-cells. 2. Patients with Favourable Prognosis. Significant increase of the absolute number of peripheral lymphocytes and B-cells. Significant increase of the spontanous DNA synthesis in the presence of AB-control-serum. Significant decrease of the T-cell function (PHA- and Con-A-stimulation in the presence of autologous serum). Significant decrease of the PHA-, Con-A- and PWM stimulation rate using control serum in the lymphocytic predominance and nodular sclerosis group. No change in the number of peripheral T-cells. 3. Patients with Unfavourable Prognosis. No change in the absolute number of B-cells, of the spontanous DNA-synthesis using autologous serum and of the PHA- and Con-A-stimulation. Significant increase of the EBV-induced blastogenesis in the mixed cellularity and lymphocytic depletion group.", "contents": "[Hodgkin's disease: effect of spenectomy on the immune status (author's transl)]. In 22 untreated Hodgkin's patients the following parameters were studied before and after splenectomy: the total WBC, lymphocytes, B- and T-cells and mitogenic stimulation of peripheral lymphocytes using autologous and control serum. The results were correlated to patient groups with favourable and unfavourable prognosis according to pathological stage, histology, spleen involvement and constitutional symptoms. 1. All Patients. Significant increase of the absolute number of peripheral lymphocytes and B-cells. Significant increase of the spontanous DNA synthesis in the presence of AB-control serum, but no change after mitogenic stimulation of peripheral lymphocytes. No change in the number of peripheral T-cells. 2. Patients with Favourable Prognosis. Significant increase of the absolute number of peripheral lymphocytes and B-cells. Significant increase of the spontanous DNA synthesis in the presence of AB-control-serum. Significant decrease of the T-cell function (PHA- and Con-A-stimulation in the presence of autologous serum). Significant decrease of the PHA-, Con-A- and PWM stimulation rate using control serum in the lymphocytic predominance and nodular sclerosis group. No change in the number of peripheral T-cells. 3. Patients with Unfavourable Prognosis. No change in the absolute number of B-cells, of the spontanous DNA-synthesis using autologous serum and of the PHA- and Con-A-stimulation. Significant increase of the EBV-induced blastogenesis in the mixed cellularity and lymphocytic depletion group."}
{"id": "PMID:211316", "title": "Abnormal low density lipoproteins in children with familial hypercholesterolemia--effect of polyanion exchange resins.", "content": "In 20 children and adolescents with familial Type II a hyperlipoproteinemia, serum lipids and lipoproteins were examined before and during treatment with polyanion exchange resins. The composition of LDL was compared to that of helthy siblings. The patients were given Colestyramine (0.6 g/kg body weight) and Colestipol (0.5 g/kg body weight) in a cross-over study for 8 weeks each, after they had been under dietary treatment for at least 12 months. In 6 children, drug treatment had to be stopped due to side-effects. The most common complaints were gastrointestinal discomfort and constipation. Cholesterol, triglycerides and phopholipids were measured in whole serum and cholesterol, triglycerides and Apolipoprotein-B in isolated lipoprotein fractions after ultracentrifugation. Apo-B was determined by radial immunodiffusion. The Apo-B: cholesterol ratio in whole serum and in the LDL fraction was identical in the patients and in the controls. The LDL triglyceride: Apo-B ratio, however, was about 50% lower in the patients. This abnormal LDL composition was not altered by therapy with polyanion exchange resins. HDL cholesterol levels were significantly lower in the patients than in healthy children, and remained low during therapy. The decrease of total and LDL cholesterol (25%) and Apo-B (20%) was similar under both Colestipol and Colestyramine. Triglycerides and phospholipids showed no significant changes in therapy.", "contents": "Abnormal low density lipoproteins in children with familial hypercholesterolemia--effect of polyanion exchange resins. In 20 children and adolescents with familial Type II a hyperlipoproteinemia, serum lipids and lipoproteins were examined before and during treatment with polyanion exchange resins. The composition of LDL was compared to that of helthy siblings. The patients were given Colestyramine (0.6 g/kg body weight) and Colestipol (0.5 g/kg body weight) in a cross-over study for 8 weeks each, after they had been under dietary treatment for at least 12 months. In 6 children, drug treatment had to be stopped due to side-effects. The most common complaints were gastrointestinal discomfort and constipation. Cholesterol, triglycerides and phopholipids were measured in whole serum and cholesterol, triglycerides and Apolipoprotein-B in isolated lipoprotein fractions after ultracentrifugation. Apo-B was determined by radial immunodiffusion. The Apo-B: cholesterol ratio in whole serum and in the LDL fraction was identical in the patients and in the controls. The LDL triglyceride: Apo-B ratio, however, was about 50% lower in the patients. This abnormal LDL composition was not altered by therapy with polyanion exchange resins. HDL cholesterol levels were significantly lower in the patients than in healthy children, and remained low during therapy. The decrease of total and LDL cholesterol (25%) and Apo-B (20%) was similar under both Colestipol and Colestyramine. Triglycerides and phospholipids showed no significant changes in therapy."}
{"id": "PMID:211348", "title": "Membrane assembly: synthesis and intracellular processing of the vesicular stomatitis viral glycoprotein.", "content": "The glycoprotein (G) of vesicular stomatitis virus (VSV) is synthesized on membrane-bound polyribosomes. Approximately 30 min after its synthesis, it reaches the surface plasma membrane where it is incorporated into budding virus. The first part of this paper focuses on the 2 intracellular, membrane-bound, glycosylated forms of the glycoprotein which are intermediates in its biogenesis. All glycosylation and processing is completed in the smooth microsome fraction before the protein reaches the surface. Next, we turn to the mechanism by which G is synthesized on membrane-bound polyribosomes. All of the G mRNA is bound to membranes, and studies with puromycin suggest that this attachment of G mRNA is mediated by the nascent glycoprotein chain. After its synthesis G is a transmembrane protein with about 30 amino acids at the carboxyl terminus remaining on the cytoplasmic side of the endoplasmic reticulum. Since 95% of the glycoprotein, containing the carbohydrate residues, is resistant to attack by external proteases, it appears to be within the lumen of the endoplasmic reticulum or embedded within the lipid bilayer. Finally, we show that synthesis, glycosylation, and proper asymmetric insertion of G into the ER can be achieved in cell-free extracts. Both glycosylation of G and proper insertion into the ER membrane in this cell-free system require concomitant protein synthesis.", "contents": "Membrane assembly: synthesis and intracellular processing of the vesicular stomatitis viral glycoprotein. The glycoprotein (G) of vesicular stomatitis virus (VSV) is synthesized on membrane-bound polyribosomes. Approximately 30 min after its synthesis, it reaches the surface plasma membrane where it is incorporated into budding virus. The first part of this paper focuses on the 2 intracellular, membrane-bound, glycosylated forms of the glycoprotein which are intermediates in its biogenesis. All glycosylation and processing is completed in the smooth microsome fraction before the protein reaches the surface. Next, we turn to the mechanism by which G is synthesized on membrane-bound polyribosomes. All of the G mRNA is bound to membranes, and studies with puromycin suggest that this attachment of G mRNA is mediated by the nascent glycoprotein chain. After its synthesis G is a transmembrane protein with about 30 amino acids at the carboxyl terminus remaining on the cytoplasmic side of the endoplasmic reticulum. Since 95% of the glycoprotein, containing the carbohydrate residues, is resistant to attack by external proteases, it appears to be within the lumen of the endoplasmic reticulum or embedded within the lipid bilayer. Finally, we show that synthesis, glycosylation, and proper asymmetric insertion of G into the ER can be achieved in cell-free extracts. Both glycosylation of G and proper insertion into the ER membrane in this cell-free system require concomitant protein synthesis."}
{"id": "PMID:211349", "title": "Small-angle x-ray scattering study of human serum low-density lipoproteins with differential reactivity for an arterial proteoglycan.", "content": "The structure and thermal behavior of human serum low-density lipoproteins showing either a high or a low reactivity against a proteoglycan isolated from human arteries have been found to be different from each other. It is suggested that modifications in the lipoprotein surface structure induced by the physical state of the neutral lipids could modulate the affinity of the macromolecule for the arterial component.", "contents": "Small-angle x-ray scattering study of human serum low-density lipoproteins with differential reactivity for an arterial proteoglycan. The structure and thermal behavior of human serum low-density lipoproteins showing either a high or a low reactivity against a proteoglycan isolated from human arteries have been found to be different from each other. It is suggested that modifications in the lipoprotein surface structure induced by the physical state of the neutral lipids could modulate the affinity of the macromolecule for the arterial component."}
{"id": "PMID:211350", "title": "Glycoprotein synthesis as a function of epithelial cell arrangement: biosynthesis and release of glycoproteins by human breast and prostate cells in organ culture.", "content": "We demonstrate that a technique is available to investigate glycoprotein synthesis in organ cultures of human breast and prostate surgical specimens where the 3-dimensional epithelial cell arrangement remains intact. Malignant breast and prostate epithelium maintained their capacity to synthesize glycoproteins for at least 3 days as followed by the incorporation of [3H]glucosamine into macromolecules. Over 70% of incorporation was by malignant cells as judged by autoradiography. Labeled glycoproteins were released into glandular lumina and consequently into the culture fluid. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed predominantly one group of macrmolecules released with an apparent molecular weight of 48,000 +/- 6,000 daltons. This glycoprotein was found in all of the breast specimens studied, which included 1 medullary, 1 infiltrating lobular, and 8 infiltrating duct carcinomas. The pattern was independent of the availability of estrogen receptors. A similar glycoprotein was also observed in the culture media from a Grade I and a Grade II well-differentiated infiltrating prostate carcinoma. Incorporation was below the level of detection in 4 of 6 cases of benign prostatic hyperplasia. A more complex pattern of labeled glycoproteins was found in the media of a Grade II and a Grade III poorly-differentiated prostate carcinoma. The established human mammary carcinoma cell line MCF-7 synthesized and released a similar 48,000 molecular weight glycoprotein but additional components with larger molecular weights were also released. An intriguing interpretation that 3-dimensional tissue integrity restricts some glycoprotein synthesis is discussed. Cells grown in 2-dimensional monolayers could escape from such a topographic restriction and express additional families of glycoproteins.", "contents": "Glycoprotein synthesis as a function of epithelial cell arrangement: biosynthesis and release of glycoproteins by human breast and prostate cells in organ culture. We demonstrate that a technique is available to investigate glycoprotein synthesis in organ cultures of human breast and prostate surgical specimens where the 3-dimensional epithelial cell arrangement remains intact. Malignant breast and prostate epithelium maintained their capacity to synthesize glycoproteins for at least 3 days as followed by the incorporation of [3H]glucosamine into macromolecules. Over 70% of incorporation was by malignant cells as judged by autoradiography. Labeled glycoproteins were released into glandular lumina and consequently into the culture fluid. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed predominantly one group of macrmolecules released with an apparent molecular weight of 48,000 +/- 6,000 daltons. This glycoprotein was found in all of the breast specimens studied, which included 1 medullary, 1 infiltrating lobular, and 8 infiltrating duct carcinomas. The pattern was independent of the availability of estrogen receptors. A similar glycoprotein was also observed in the culture media from a Grade I and a Grade II well-differentiated infiltrating prostate carcinoma. Incorporation was below the level of detection in 4 of 6 cases of benign prostatic hyperplasia. A more complex pattern of labeled glycoproteins was found in the media of a Grade II and a Grade III poorly-differentiated prostate carcinoma. The established human mammary carcinoma cell line MCF-7 synthesized and released a similar 48,000 molecular weight glycoprotein but additional components with larger molecular weights were also released. An intriguing interpretation that 3-dimensional tissue integrity restricts some glycoprotein synthesis is discussed. Cells grown in 2-dimensional monolayers could escape from such a topographic restriction and express additional families of glycoproteins."}
{"id": "PMID:211352", "title": "Viral infections.", "content": "In summary, viral infections of the skin that occur at adolescence include those typical of childhood and those associated with sexual maturity. Herpes simplex Type II, molluscum contagiosum, and venereal warts, diseases that have shown a marked increase, are in the latter group. Certain diseases, such as rubella, herpes simplex, varicella, and condylomata acuminata, which may lead to laryngeal papillomas, are particularly important because of their effects on the newborn infant. The epidemiological pattern of viral infections changes, and new viruses gain prominence while others fade in importance as causes of disease. Because of this, we can expect new viral entities and changes in earlier ones.", "contents": "Viral infections. In summary, viral infections of the skin that occur at adolescence include those typical of childhood and those associated with sexual maturity. Herpes simplex Type II, molluscum contagiosum, and venereal warts, diseases that have shown a marked increase, are in the latter group. Certain diseases, such as rubella, herpes simplex, varicella, and condylomata acuminata, which may lead to laryngeal papillomas, are particularly important because of their effects on the newborn infant. The epidemiological pattern of viral infections changes, and new viruses gain prominence while others fade in importance as causes of disease. Because of this, we can expect new viral entities and changes in earlier ones."}
{"id": "PMID:211355", "title": "Evidence for increased degeneration of mitochondria in old rats. A brief note.", "content": "An isotonic density gradient technique for separating mitochondria into two major components was applied to mitochondria isolated from young and old rats. Respiratory measuremtns indicate that the depression of state 3 respiration rates observed in the mitochondria from old rats when glutamate--malate is used as a substrate is due primarily to the faster sedimenting mitochondrial component.", "contents": "Evidence for increased degeneration of mitochondria in old rats. A brief note. An isotonic density gradient technique for separating mitochondria into two major components was applied to mitochondria isolated from young and old rats. Respiratory measuremtns indicate that the depression of state 3 respiration rates observed in the mitochondria from old rats when glutamate--malate is used as a substrate is due primarily to the faster sedimenting mitochondrial component."}
{"id": "PMID:211356", "title": "Studies of age-related changes in the metabolism of eosin in the rat.", "content": "Male rats of different age groups maintained normally on laboratory chow were injected with eosin (2,4,5,7-tetrabromo-11-carboxyfluorescein) after which the biliary excretion of the dye was studied. In 3 age groups below 42 weeks, the dye was excreted as 2 compounds which were identified by thin-layer chromatography as unchanged eosin (Rf 0.90--0.91) contributing about 80--90% and one conjugated compound of Rf 0.43--0.47 (14--9%) which was shown to be a glucuronide. Eosin metabolites could not be traced in 30 and 42 week-old rats. This finding is discussed in relation to: (i) age and enzymic activity, and (ii) bio-activated metabolites of this dye which may induce biochemical or toxicological and carcinogenic lesions.", "contents": "Studies of age-related changes in the metabolism of eosin in the rat. Male rats of different age groups maintained normally on laboratory chow were injected with eosin (2,4,5,7-tetrabromo-11-carboxyfluorescein) after which the biliary excretion of the dye was studied. In 3 age groups below 42 weeks, the dye was excreted as 2 compounds which were identified by thin-layer chromatography as unchanged eosin (Rf 0.90--0.91) contributing about 80--90% and one conjugated compound of Rf 0.43--0.47 (14--9%) which was shown to be a glucuronide. Eosin metabolites could not be traced in 30 and 42 week-old rats. This finding is discussed in relation to: (i) age and enzymic activity, and (ii) bio-activated metabolites of this dye which may induce biochemical or toxicological and carcinogenic lesions."}
{"id": "PMID:211357", "title": "[Spiradenoma, cutaneous cylindroma and familial multiple trichoepithelioma].", "content": "Multiple spiradenoma, trichoepithelioma and traits of cylindroma in three members of a family are studied. The relationships among these tumors are discussed. Spiroadenoma and cynlindroma have shown a close interrelation. Both conditions may exist with multiple lesions in genetic autosomal dominant inherited association with multiple trichoepitelioma.", "contents": "[Spiradenoma, cutaneous cylindroma and familial multiple trichoepithelioma]. Multiple spiradenoma, trichoepithelioma and traits of cylindroma in three members of a family are studied. The relationships among these tumors are discussed. Spiroadenoma and cynlindroma have shown a close interrelation. Both conditions may exist with multiple lesions in genetic autosomal dominant inherited association with multiple trichoepitelioma."}
{"id": "PMID:211368", "title": "Altered mechanism of glucagon-mediated hepatic glycogenolysis during long-term starvation in the rat.", "content": "The effect of long-term starvation on glucagon-mediated hepatic glycogenolysis was investigated in the rat in vivo. Following glucagon (50 microgram/kg i.v.) fed rats showed rapid phosphorylase activation but no change in synthase-I activities. In contrast, rats fasted 72 hr (long-term fasting) showed rapid synthase inactivation but no significant phosphorylase activation. Rats fasted 24 hr (short-term fasting) demonstrated coordinated inactivation of synthase and activation of phosphorylase. Hepatic cyclic AMP responses were greater in fasted rats. Hepatic glycogen concentrations in rats fasted 72 hr were approximately 30% of fed levels. After glucagon, comparable decrements in hepatic glycogen and increments in plasma glucose concentrations were seen in fed and 72-hr groups. The diminished responsiveness of the hepatic phosphorylase system in rats fasted 72 hr was not attributable to altered cyclic AMP-dependent protein kinase or phosphorylase kinase activities. However, the diminished responsiveness could be ascribed to diminished total phosphorylase with nearly complete activation in the basal state. In fed and fasted rats, synthase decrements after glucagon correlated closely with basal levels of synthase-I. Thus, it is proposed that the enzymatic mechanism of glucagon-mediated hepatic glycogenolysis differs in fed and fasted rats. It is also proposed that partial hepatic glycogen reaccumulation during long-term fasting could be physiologically important for glucose homeostasis.", "contents": "Altered mechanism of glucagon-mediated hepatic glycogenolysis during long-term starvation in the rat. The effect of long-term starvation on glucagon-mediated hepatic glycogenolysis was investigated in the rat in vivo. Following glucagon (50 microgram/kg i.v.) fed rats showed rapid phosphorylase activation but no change in synthase-I activities. In contrast, rats fasted 72 hr (long-term fasting) showed rapid synthase inactivation but no significant phosphorylase activation. Rats fasted 24 hr (short-term fasting) demonstrated coordinated inactivation of synthase and activation of phosphorylase. Hepatic cyclic AMP responses were greater in fasted rats. Hepatic glycogen concentrations in rats fasted 72 hr were approximately 30% of fed levels. After glucagon, comparable decrements in hepatic glycogen and increments in plasma glucose concentrations were seen in fed and 72-hr groups. The diminished responsiveness of the hepatic phosphorylase system in rats fasted 72 hr was not attributable to altered cyclic AMP-dependent protein kinase or phosphorylase kinase activities. However, the diminished responsiveness could be ascribed to diminished total phosphorylase with nearly complete activation in the basal state. In fed and fasted rats, synthase decrements after glucagon correlated closely with basal levels of synthase-I. Thus, it is proposed that the enzymatic mechanism of glucagon-mediated hepatic glycogenolysis differs in fed and fasted rats. It is also proposed that partial hepatic glycogen reaccumulation during long-term fasting could be physiologically important for glucose homeostasis."}
{"id": "PMID:211370", "title": "Hormonal regulation of membrane receptors and cell responsiveness: a review.", "content": "Hormone receptors are those components of target-cells that specifically bind hormones and convey the hormonal message to the intracellular machinery. Such receptors can be localized inside the cell, such as the nuclear receptors of thyroid hormones and the nuclear and cytoplasmic receptors of steroid hormones, or on the outer surface of the plasma membrane, such as the membrane-bound receptors of polypeptide hormones and neurotransmitters. Extensive studies during recent years have shown that the interaction between hormone and membrane-bound receptor can affect the receptor characteristics in at least two ways. Firstly, receptor occupancy can modify, by way of cooperativity, the affinity of homologue receptors for the given hormone. Secondly, the binding capacity of a target cell appears to vary as a function of the preexposure of the cell to the hormone. The latter phenomenon has been related to the so-called states of subsensitivity, desensitization, or refractoriness, and might be responsible for the physiologic regulation of the target cell sensitivity and for the hormone resistance which accompanies various metabolic disorders. In this review we attempt to describe the major findings related to hormone desensitization or resistance of these hormones that have plasma-membrane-bound receptors. Data from the literature are presented independently for each hormone and when applicable, conflicting results are discussed in each section. The various theories which might explain hormone desensitization are outlined in the last section of this paper.", "contents": "Hormonal regulation of membrane receptors and cell responsiveness: a review. Hormone receptors are those components of target-cells that specifically bind hormones and convey the hormonal message to the intracellular machinery. Such receptors can be localized inside the cell, such as the nuclear receptors of thyroid hormones and the nuclear and cytoplasmic receptors of steroid hormones, or on the outer surface of the plasma membrane, such as the membrane-bound receptors of polypeptide hormones and neurotransmitters. Extensive studies during recent years have shown that the interaction between hormone and membrane-bound receptor can affect the receptor characteristics in at least two ways. Firstly, receptor occupancy can modify, by way of cooperativity, the affinity of homologue receptors for the given hormone. Secondly, the binding capacity of a target cell appears to vary as a function of the preexposure of the cell to the hormone. The latter phenomenon has been related to the so-called states of subsensitivity, desensitization, or refractoriness, and might be responsible for the physiologic regulation of the target cell sensitivity and for the hormone resistance which accompanies various metabolic disorders. In this review we attempt to describe the major findings related to hormone desensitization or resistance of these hormones that have plasma-membrane-bound receptors. Data from the literature are presented independently for each hormone and when applicable, conflicting results are discussed in each section. The various theories which might explain hormone desensitization are outlined in the last section of this paper."}
{"id": "PMID:211399", "title": "Properties of the erythrocyte receptors for influenza C virus.", "content": "Properties of the receptor for influenza C virus were studied. Although the receptor for influenza C virus on chicken erythrocytes was destroyed by the homologous virion, neuraminidase activity could not be detected in any of the influenza C virus strains tested. The receptor activity of chicken erythrocytes for influenza C virus was diminished by formaldehyde treatment but not by periodate oxidation. There was a considerable variation in the pattern and the titer of hemagglutination of influenza C virus when human erythrocytes of different blood types were used; the virus agglutinated most type B erythrocytes but not type A erythrocytes. By using human type B erythrocytes, differences among strains of influenza C virus in the hemagglutinating activity were also demonstrated. These results showed that both the receptor for and the receptor-destroying activity of influenza C virus were completely different from those of influenza A or B virus and also that carbohydrates were not involved in the receptor for influenza C virus.", "contents": "Properties of the erythrocyte receptors for influenza C virus. Properties of the receptor for influenza C virus were studied. Although the receptor for influenza C virus on chicken erythrocytes was destroyed by the homologous virion, neuraminidase activity could not be detected in any of the influenza C virus strains tested. The receptor activity of chicken erythrocytes for influenza C virus was diminished by formaldehyde treatment but not by periodate oxidation. There was a considerable variation in the pattern and the titer of hemagglutination of influenza C virus when human erythrocytes of different blood types were used; the virus agglutinated most type B erythrocytes but not type A erythrocytes. By using human type B erythrocytes, differences among strains of influenza C virus in the hemagglutinating activity were also demonstrated. These results showed that both the receptor for and the receptor-destroying activity of influenza C virus were completely different from those of influenza A or B virus and also that carbohydrates were not involved in the receptor for influenza C virus."}
{"id": "PMID:211407", "title": "Conditions necessary for quantifying ethyl methanesulfonate-induced mutations to purine-analogue resistance in Chinese hamster V79 cells.", "content": "We have investigated conditions necessary to quantify the relationship between exposure to a mutagen, ethyl methanesulfonate (EMS), and the frequency of mutation induction at the hypoxanthine-guanine phosphoribosyl transferase locus in V79 cells. Maximal expression of potential mutants has been achieved by either subculturing at fewer than 5 X 10(5) cells/100-mm dish at 2-day intervals or by daily feeding of cultures. An expression period of 5 days (measure from 1 day after the initiation of treatment with the chemical mutagen) should be allowed, since at least 4 days of expression is required to reach to steady maximum of mutation frequency. It appears that there is no concentration dependence of expression time necessary to reach a plateau of mutation frequency with increasing concentrations of EMS up to 1.6 mg/ml. About 1.25 X 10(5) cells/100-mm dish or fewer should be plated for selection to avoid the loss of mutants which occurs at 1.5 X 10(5) cells/dish, presumably through cross-feeding (metabolic cooperation). The use of 6-thioguanine in hypoxanthine-free medium (supplemented with dialyzed fetal calf serum) appears to be a very stringent condition for selection. Mutation induction by EMS as a function of EMS exposure (EMS concentration X treatment time) increases linearly with concentration up to 12 h. For these treatment periods, the observed mutation frequencies for EMS are directly proportional to mutagen exposure regardless of the duration of the treatment.", "contents": "Conditions necessary for quantifying ethyl methanesulfonate-induced mutations to purine-analogue resistance in Chinese hamster V79 cells. We have investigated conditions necessary to quantify the relationship between exposure to a mutagen, ethyl methanesulfonate (EMS), and the frequency of mutation induction at the hypoxanthine-guanine phosphoribosyl transferase locus in V79 cells. Maximal expression of potential mutants has been achieved by either subculturing at fewer than 5 X 10(5) cells/100-mm dish at 2-day intervals or by daily feeding of cultures. An expression period of 5 days (measure from 1 day after the initiation of treatment with the chemical mutagen) should be allowed, since at least 4 days of expression is required to reach to steady maximum of mutation frequency. It appears that there is no concentration dependence of expression time necessary to reach a plateau of mutation frequency with increasing concentrations of EMS up to 1.6 mg/ml. About 1.25 X 10(5) cells/100-mm dish or fewer should be plated for selection to avoid the loss of mutants which occurs at 1.5 X 10(5) cells/dish, presumably through cross-feeding (metabolic cooperation). The use of 6-thioguanine in hypoxanthine-free medium (supplemented with dialyzed fetal calf serum) appears to be a very stringent condition for selection. Mutation induction by EMS as a function of EMS exposure (EMS concentration X treatment time) increases linearly with concentration up to 12 h. For these treatment periods, the observed mutation frequencies for EMS are directly proportional to mutagen exposure regardless of the duration of the treatment."}
{"id": "PMID:211411", "title": "Prolactin-screening tumors and hypogonadism in 22 men.", "content": "We studied 22 men with prolactin-secreting pituitary tumors and hypogonadism. Twenty complained of impotence, nine had visual impairment, and three experienced galactorrhea. None of the 17 patients undergoing operation or radiotherapy, or both, were subsequently normoprolactinemic. In all 13 patients treated with bromocryptine major clinical improvement was associated with a decrease in serum prolactin levels and in nine with an increase in serum testosterone. Two patients receiving testosterone replacement therapy showed improved potency only after bromocryptine was administered. The results indicate that hyperprolactinemia frequently induces hypogonadism in men, that bromocryptine ameliorates symptoms of disease previously unchanged by operation or radiotherapy, and that the impotence observed may not be solely the result of hypogonadism.", "contents": "Prolactin-screening tumors and hypogonadism in 22 men. We studied 22 men with prolactin-secreting pituitary tumors and hypogonadism. Twenty complained of impotence, nine had visual impairment, and three experienced galactorrhea. None of the 17 patients undergoing operation or radiotherapy, or both, were subsequently normoprolactinemic. In all 13 patients treated with bromocryptine major clinical improvement was associated with a decrease in serum prolactin levels and in nine with an increase in serum testosterone. Two patients receiving testosterone replacement therapy showed improved potency only after bromocryptine was administered. The results indicate that hyperprolactinemia frequently induces hypogonadism in men, that bromocryptine ameliorates symptoms of disease previously unchanged by operation or radiotherapy, and that the impotence observed may not be solely the result of hypogonadism."}
{"id": "PMID:211412", "title": "Metabolism of high-density lipoprotein apolipoproteins in Tangier disease.", "content": "To define the metabolic defect in Tangier disease, we studied the kinetics of [125I]-high-density lipoprotein apolipoproteins (apolipoproteins A-I and A-II) in 11 normal subjects, two obligate heterozygotes, and two homozygotes. Mean synthesis of apolipoproteins A-1 and A-11 was 8.24 mg per kilogram per day in the normal group, 7.94 in heterozygotes and 3.66 in homozygotes. The mean plasma-residence time for both apolipoproteins was 5.21 days in the normal subjects, 3.41 days in heterozygotes, and 0.52 days in homozygotes. In normal subjects and heterozygotes the apolipoproteins were catabolized at similar rates, whereas in homozygotes apolipoprotein A-I was catabolized at a much greater fractional rate than apolipoprotein A-II. These findings indicate that the deficiency of these apolipoproteins in Tangier disease is largely due to rapid and altered catabolism.", "contents": "Metabolism of high-density lipoprotein apolipoproteins in Tangier disease. To define the metabolic defect in Tangier disease, we studied the kinetics of [125I]-high-density lipoprotein apolipoproteins (apolipoproteins A-I and A-II) in 11 normal subjects, two obligate heterozygotes, and two homozygotes. Mean synthesis of apolipoproteins A-1 and A-11 was 8.24 mg per kilogram per day in the normal group, 7.94 in heterozygotes and 3.66 in homozygotes. The mean plasma-residence time for both apolipoproteins was 5.21 days in the normal subjects, 3.41 days in heterozygotes, and 0.52 days in homozygotes. In normal subjects and heterozygotes the apolipoproteins were catabolized at similar rates, whereas in homozygotes apolipoprotein A-I was catabolized at a much greater fractional rate than apolipoprotein A-II. These findings indicate that the deficiency of these apolipoproteins in Tangier disease is largely due to rapid and altered catabolism."}
{"id": "PMID:211413", "title": "Obstructive sleep apnea in family members.", "content": "Two sons and their father had severe hypersomnolence and obstructive sleep apnea. A third son, although asymptomatic, was shown to have upper-airway obstruction during sleep. Electromyographic recordings of genioglossus activity in the two symptomatic sons revealed loss of tonic activity in early stages of sleep at times when sleep apnea occurred. The asymptomatic son showed loss of tonic activity during rapid-eye-movement sleep, the sleep period when upper-airway obstruction occurred. Two sudden deaths occurred in this family. A 30-year-old brother died at home while asleep, and a child of the asymptomatic brother died at the age of four months from presumed sudden-infant-death syndrome. Obstructive sleep apnea may have a familial basis; the tongue may be involved in the genesis of upper-airway obstruction during sleep.", "contents": "Obstructive sleep apnea in family members. Two sons and their father had severe hypersomnolence and obstructive sleep apnea. A third son, although asymptomatic, was shown to have upper-airway obstruction during sleep. Electromyographic recordings of genioglossus activity in the two symptomatic sons revealed loss of tonic activity in early stages of sleep at times when sleep apnea occurred. The asymptomatic son showed loss of tonic activity during rapid-eye-movement sleep, the sleep period when upper-airway obstruction occurred. Two sudden deaths occurred in this family. A 30-year-old brother died at home while asleep, and a child of the asymptomatic brother died at the age of four months from presumed sudden-infant-death syndrome. Obstructive sleep apnea may have a familial basis; the tongue may be involved in the genesis of upper-airway obstruction during sleep."}
{"id": "PMID:211414", "title": "Cellular immune response in genital herpes simplex virus infection.", "content": "We studied the relations between the cellular immune response, pre-existing complement-fixing antibody and virus type with duration of virus excretion in genital herpes simplex virus (HSV) infection. Thirty-six patients (seven with HSV-1 and 29 with HSV-2) with genital herpes underwent serologic testing, sequential viral cultures and weekly determination of lymphocyte-transformation stimulation index with inactivated HSV antic n. The duration of virus excretion was shortest in those with pre-existing complement-fixing antibody, was unrelated to virus type, and was inversely correlated with the magnitude of the mean peak stimulation index (r = -0.69, P less than 0.001). Prolonged virus excretion occurred in patients with a delayed and diminished peak index. Recurrent episodes had a higher peak index (29.4 compared to 14.5) (P less than 0.02), an earlier development of the peak during recurrences (9.1 vs. 25.8 days) (P less than 0.01) and a briefer duration of viral shedding than initial episodes. Thus, the temporal course and magnitude of the stimulation index correlate with and may determine the duration of genital HSV infection.", "contents": "Cellular immune response in genital herpes simplex virus infection. We studied the relations between the cellular immune response, pre-existing complement-fixing antibody and virus type with duration of virus excretion in genital herpes simplex virus (HSV) infection. Thirty-six patients (seven with HSV-1 and 29 with HSV-2) with genital herpes underwent serologic testing, sequential viral cultures and weekly determination of lymphocyte-transformation stimulation index with inactivated HSV antic n. The duration of virus excretion was shortest in those with pre-existing complement-fixing antibody, was unrelated to virus type, and was inversely correlated with the magnitude of the mean peak stimulation index (r = -0.69, P less than 0.001). Prolonged virus excretion occurred in patients with a delayed and diminished peak index. Recurrent episodes had a higher peak index (29.4 compared to 14.5) (P less than 0.02), an earlier development of the peak during recurrences (9.1 vs. 25.8 days) (P less than 0.01) and a briefer duration of viral shedding than initial episodes. Thus, the temporal course and magnitude of the stimulation index correlate with and may determine the duration of genital HSV infection."}
{"id": "PMID:211415", "title": "[Release of toxic agents from ceramic utensils].", "content": "Under the influence of acidic agents, ceramic glazes and decorations for ceramics may release certain toxicants, especially lead and cadmium. Both elements are essential constituents of ceramic colours and glazes; their release to acidic foods is technologically unavoidable, but it may be minimized by the utilization of appropriate decoration agents and techniques. In most industrial countries, the release of toxicants from utensils is severely limited, the maximum permissible values and the methods of test and analysis being in part very different and not always in agreement with the demands and conditions of practice. The problems related to the release of toxicants from ceramic utensils are treated from the aspects of ceramics, test techniques, analytics, toxicology and food law, with special regard to the necessity for a well-balanced compromise between the justified hygienic demands of health protection and the actual technological possibilities. The endeavours of the ceramic industry of the GDF to produce ceramic utensils releasing as little toxicants as possible are outlined.", "contents": "[Release of toxic agents from ceramic utensils]. Under the influence of acidic agents, ceramic glazes and decorations for ceramics may release certain toxicants, especially lead and cadmium. Both elements are essential constituents of ceramic colours and glazes; their release to acidic foods is technologically unavoidable, but it may be minimized by the utilization of appropriate decoration agents and techniques. In most industrial countries, the release of toxicants from utensils is severely limited, the maximum permissible values and the methods of test and analysis being in part very different and not always in agreement with the demands and conditions of practice. The problems related to the release of toxicants from ceramic utensils are treated from the aspects of ceramics, test techniques, analytics, toxicology and food law, with special regard to the necessity for a well-balanced compromise between the justified hygienic demands of health protection and the actual technological possibilities. The endeavours of the ceramic industry of the GDF to produce ceramic utensils releasing as little toxicants as possible are outlined."}
{"id": "PMID:211416", "title": "[Evaluation of the cadmium content in sedimented and floating dust as factors in contamination of the biosphere].", "content": "In a territory being 3.500 km2, the cadmium deposits from the atmosphere were determined at 63 sites in 52 towns and communities. These determinations yielded a mean value ranging from 0.13 to 0.15 mg/m2 . 30 d. On the contrary, the mean value (-x) was 0.33 mg/m2. 30 d in the region of heavy-metal-emitting industries. The mean cadmium content in the aerosol was between 0.003 and 0.004 microgram m-3 and, respectively, 0.016 microgram m-3 in case of cadmium emission. It was calculated that the mean proportion of cadmium in the sedimentary dust was between 13 and 16 p.p.m. The cadmium burden, as estimated as cadmium sediment, correlated with the extent of the developmental area. The authors recommend for the present the following maximum permissible values: 0.05 microgram m-3 in the aerosol, and 0.15 mg/m2. 30 d. The cadmium content in the sedimentary dust may be considered to be a permanent burden applied via the food chain, whereas the content in the aerosol is of less importance to the total uptake in man. The calculation of the daily pulmonary uptake yielded a value of 0.075 microgram, from which an absorption of 0.038 microgram is estimated.", "contents": "[Evaluation of the cadmium content in sedimented and floating dust as factors in contamination of the biosphere]. In a territory being 3.500 km2, the cadmium deposits from the atmosphere were determined at 63 sites in 52 towns and communities. These determinations yielded a mean value ranging from 0.13 to 0.15 mg/m2 . 30 d. On the contrary, the mean value (-x) was 0.33 mg/m2. 30 d in the region of heavy-metal-emitting industries. The mean cadmium content in the aerosol was between 0.003 and 0.004 microgram m-3 and, respectively, 0.016 microgram m-3 in case of cadmium emission. It was calculated that the mean proportion of cadmium in the sedimentary dust was between 13 and 16 p.p.m. The cadmium burden, as estimated as cadmium sediment, correlated with the extent of the developmental area. The authors recommend for the present the following maximum permissible values: 0.05 microgram m-3 in the aerosol, and 0.15 mg/m2. 30 d. The cadmium content in the sedimentary dust may be considered to be a permanent burden applied via the food chain, whereas the content in the aerosol is of less importance to the total uptake in man. The calculation of the daily pulmonary uptake yielded a value of 0.075 microgram, from which an absorption of 0.038 microgram is estimated."}
{"id": "PMID:211417", "title": "Transmission of hormonal stimulation by cell-to-cell communication.", "content": "Rat ovarian granulosa cells and mouse myocardial cells respond to cell-specific hormones by cyclic AMP-dependent mechanisms. In coculture, these heterologous cells communicate by means of gap junctions. Exposure of the cocultures to a hormone specific for one cell type causes the heterologous cells to respond through a cell contact-dependent mechanism. These studies suggest that this cross-stimulation results from the intercellular communication of a mediator that is common to both cell types. The communicated mediator may be cyclic AMP.", "contents": "Transmission of hormonal stimulation by cell-to-cell communication. Rat ovarian granulosa cells and mouse myocardial cells respond to cell-specific hormones by cyclic AMP-dependent mechanisms. In coculture, these heterologous cells communicate by means of gap junctions. Exposure of the cocultures to a hormone specific for one cell type causes the heterologous cells to respond through a cell contact-dependent mechanism. These studies suggest that this cross-stimulation results from the intercellular communication of a mediator that is common to both cell types. The communicated mediator may be cyclic AMP."}
{"id": "PMID:211428", "title": "Neuronal properties underlying processing of visual information in the barnacle.", "content": "Generation of a transient, amplified response to the dimming of light in the visual system of the barnacle involves two synaptic stages. It is accomplished primarily by decrementally conducting neurones that are similar to bipolar cells of the vertebrate retina.", "contents": "Neuronal properties underlying processing of visual information in the barnacle. Generation of a transient, amplified response to the dimming of light in the visual system of the barnacle involves two synaptic stages. It is accomplished primarily by decrementally conducting neurones that are similar to bipolar cells of the vertebrate retina."}
{"id": "PMID:211433", "title": "Promoter-specific inhibition of transcription by antibiotics which act on DNA gyrase.", "content": "Nalidixic acid, novobiocin and coumermycin specifically inhibit phage promoter-dependent transcription of the trp operon in phi 80 ptrp but not transcription from the authentic trp promoter. The nalidixic acid inhibition is not observed in an E. coli strain containing a nalAr mutation. These results indicate that DNA gyrase is involved in transcription.", "contents": "Promoter-specific inhibition of transcription by antibiotics which act on DNA gyrase. Nalidixic acid, novobiocin and coumermycin specifically inhibit phage promoter-dependent transcription of the trp operon in phi 80 ptrp but not transcription from the authentic trp promoter. The nalidixic acid inhibition is not observed in an E. coli strain containing a nalAr mutation. These results indicate that DNA gyrase is involved in transcription."}
{"id": "PMID:211440", "title": "Temperature-sensitive mutant of avian erythroblastosis virus suggests a block of differentiation as mechanism of leukaemogenesis.", "content": "A temperature sensitive mutant has been isolated for the first time from a replication defective acute leukaemia virus, AEV. In vivo, at 41 degrees C, the mutant shows a reduced leukaemogenic potential. In vitro, in erythroblasts transformed at 35 degrees C, haemoglobin synthesis can be induced by a shift to 41 degrees C. This indicates that the continuous expression of a viral gene product is necessary to maintain the undifferentiated state of the virus-transformed leukaemia cells.", "contents": "Temperature-sensitive mutant of avian erythroblastosis virus suggests a block of differentiation as mechanism of leukaemogenesis. A temperature sensitive mutant has been isolated for the first time from a replication defective acute leukaemia virus, AEV. In vivo, at 41 degrees C, the mutant shows a reduced leukaemogenic potential. In vitro, in erythroblasts transformed at 35 degrees C, haemoglobin synthesis can be induced by a shift to 41 degrees C. This indicates that the continuous expression of a viral gene product is necessary to maintain the undifferentiated state of the virus-transformed leukaemia cells."}
{"id": "PMID:211443", "title": "Passive immunization against transmissible gastroenteritis virus in piglets by ingestion of milk of sows inoculated with attenuated virus.", "content": "Pregnant sows were inoculated with the attenuated strain, TO--163, of swine transmissible gastroenteritis virus. Suckling piglets born from them received challenge inoculation with the virulent virus at 3 days after birth, and examined for ability to prevent infection and the immunoglobulin (Ig) classes of antibody in milk. A pregnant sow was inoculated intramuscularly with a dose of 10(8.0) TCID50 and intranasally with a dose of 10(9.3) TCID50 of attenuated virus. Piglets born from it suffered from diarrhea after challenge inoculation, but none of them died eventually. Their dam was also affected with diarrhea for 4 to 7 days after challenge inoculation of them. Another pregnant sow was inoculated twice with 10(9.3) TCID50 of attenuated virus, first by the intramuscular and secondly by the intranasal route. Of nine piglets born from it, one excreted soft feces after challenge inoculation, but all survived to grow normally. Their dam manifested no clinical symptoms at all after challenge inoculation of them. The higher the titer of virus inoculated into pregnant sows, the higher the neutralizing antibody titer in serum and milk of the sows after farrowing. The puerperal sow which had received two doses of 10(9.3) TCID50 each of attenuated virus by the intramuscular and intranasal route, respectively, presented the highest neutralizing antibody titer of all the inoculated sows. This titer was 2,048 in serum and 14,183 in colostrum immediately after farrowing. In that sow IgG was the main class of immunoglobulins in neutralizing antibody in milk. Even the IgA antibody titer of that sow was higher than that of any other sow which had been administered with virus of low titer. It was 392 and 19 3 and 9 days, respectively, after farrowing.", "contents": "Passive immunization against transmissible gastroenteritis virus in piglets by ingestion of milk of sows inoculated with attenuated virus. Pregnant sows were inoculated with the attenuated strain, TO--163, of swine transmissible gastroenteritis virus. Suckling piglets born from them received challenge inoculation with the virulent virus at 3 days after birth, and examined for ability to prevent infection and the immunoglobulin (Ig) classes of antibody in milk. A pregnant sow was inoculated intramuscularly with a dose of 10(8.0) TCID50 and intranasally with a dose of 10(9.3) TCID50 of attenuated virus. Piglets born from it suffered from diarrhea after challenge inoculation, but none of them died eventually. Their dam was also affected with diarrhea for 4 to 7 days after challenge inoculation of them. Another pregnant sow was inoculated twice with 10(9.3) TCID50 of attenuated virus, first by the intramuscular and secondly by the intranasal route. Of nine piglets born from it, one excreted soft feces after challenge inoculation, but all survived to grow normally. Their dam manifested no clinical symptoms at all after challenge inoculation of them. The higher the titer of virus inoculated into pregnant sows, the higher the neutralizing antibody titer in serum and milk of the sows after farrowing. The puerperal sow which had received two doses of 10(9.3) TCID50 each of attenuated virus by the intramuscular and intranasal route, respectively, presented the highest neutralizing antibody titer of all the inoculated sows. This titer was 2,048 in serum and 14,183 in colostrum immediately after farrowing. In that sow IgG was the main class of immunoglobulins in neutralizing antibody in milk. Even the IgA antibody titer of that sow was higher than that of any other sow which had been administered with virus of low titer. It was 392 and 19 3 and 9 days, respectively, after farrowing."}
{"id": "PMID:211444", "title": "The use of polyethylene glycol in concentration and purification of several bovine viruses.", "content": "The polyethylene glycol (PEG) precipitation method was used for the concentration and purification of eight bovine viruses. Good results were obtained from four viruses, parainfluenza--3 virus, bovine enterovirus, bovine adenovirus, and bovine parvovirus. No satisfactory results of concentration were obtained from bovine reovirus, bovine viral diarrhea virus, and infectious bovine rhinotracheitis virus. The failure of concentration of the four viruses seems to be ascribed rather to the resuspending of virus from the virus--PEG precipitate than to the precipitation of virus from infective culture fluid. This method can be applied as the initial step to the concentration of parainfluenza--3 virus, bovine enterovirus, bovine adenovirus, and bovine parvovirus from a large volume of material, since it is simple, rapid, and inexpensive.", "contents": "The use of polyethylene glycol in concentration and purification of several bovine viruses. The polyethylene glycol (PEG) precipitation method was used for the concentration and purification of eight bovine viruses. Good results were obtained from four viruses, parainfluenza--3 virus, bovine enterovirus, bovine adenovirus, and bovine parvovirus. No satisfactory results of concentration were obtained from bovine reovirus, bovine viral diarrhea virus, and infectious bovine rhinotracheitis virus. The failure of concentration of the four viruses seems to be ascribed rather to the resuspending of virus from the virus--PEG precipitate than to the precipitation of virus from infective culture fluid. This method can be applied as the initial step to the concentration of parainfluenza--3 virus, bovine enterovirus, bovine adenovirus, and bovine parvovirus from a large volume of material, since it is simple, rapid, and inexpensive."}
{"id": "PMID:211445", "title": "Responses of the rat superior cervical ganglion in vitro to isoprenaline and bethanechol.", "content": "The effects of isoprenaline were studied in isolated rat superior cervical ganglia. Intracellularly recorded excitatory postsynaptic potentials were depressed by isoprenaline in concentrations of 10(-5) to 10(-4)M. In 13 out of 17 cells, isoprenaline caused ganglionic hyperpolarization (mean, 4mV). Changes in the amplitude and contour of antidromic action potentials caused by isoprenaline could be accounted for by the increased membrane potential. A slight increase in membrane input resistance from 44--50.2 megohms (mean values) occurred in about half of the cells. Activation of an ion pump by isoprenaline was suggested by the finding that the hyperpolarization did not occur when the bathing solution contained ouabain (10(-5)M) or lacked Na+ or K+. Characterization of the isoprenaline effects by the use of alpha and beta adrenergic blocking drugs was not possible because of the direct depressant effects of the antagonists. The muscarinic agonist bethanechol (2.5 X 10(-5) to 2.5 X 10(-4)M) caused ganglionic depolarization and increased input membrane resistance (42--52 megohms) during depolarization in each of the cells tested. The ganglionic responses to bethanechol were prevented by atropine.", "contents": "Responses of the rat superior cervical ganglion in vitro to isoprenaline and bethanechol. The effects of isoprenaline were studied in isolated rat superior cervical ganglia. Intracellularly recorded excitatory postsynaptic potentials were depressed by isoprenaline in concentrations of 10(-5) to 10(-4)M. In 13 out of 17 cells, isoprenaline caused ganglionic hyperpolarization (mean, 4mV). Changes in the amplitude and contour of antidromic action potentials caused by isoprenaline could be accounted for by the increased membrane potential. A slight increase in membrane input resistance from 44--50.2 megohms (mean values) occurred in about half of the cells. Activation of an ion pump by isoprenaline was suggested by the finding that the hyperpolarization did not occur when the bathing solution contained ouabain (10(-5)M) or lacked Na+ or K+. Characterization of the isoprenaline effects by the use of alpha and beta adrenergic blocking drugs was not possible because of the direct depressant effects of the antagonists. The muscarinic agonist bethanechol (2.5 X 10(-5) to 2.5 X 10(-4)M) caused ganglionic depolarization and increased input membrane resistance (42--52 megohms) during depolarization in each of the cells tested. The ganglionic responses to bethanechol were prevented by atropine."}
{"id": "PMID:211447", "title": "Correlation between inhibition of (Na+, K+)-membrane-ATPase and positive inotropic activity of cardenolides in isolated papillary muscles of guinea pig.", "content": "Concentrations of 17 cardenolides, cardenolide glucuronides and sulfates producing half-maximal inhibition of (Na+, K+)-membrane-ATPase from different organs and animal species were determined in vitro. In addition the concentrations that increased the contractility of guinea pig isolated papillary muscles to a particular level were investigated. Comparisons between ATPase-inhibiting and positive inotropic cardiac activities showed extensive parallelism: the correlation coefficients after log/log transformation were between 0.92 and 0.97. The same close correlations are found if dissociation constants of cardenolide receptor complexes and concentrations causing 86Rb-uptake inhibition in human erythrocytes are examined. The concentrations necessary for inhibition of (Na+, K+)-membrane-ATPase of the guinea pig heart and the concentrations required to achieve a defined positive inotropic effect in guinea pig papillary muscle showed a log/log correlation coefficient of 0.97 (P less than 0.001). In both tests the potencies covered more than three orders of magnitude. The results support Repke's hypothesis on the digitalis receptor.", "contents": "Correlation between inhibition of (Na+, K+)-membrane-ATPase and positive inotropic activity of cardenolides in isolated papillary muscles of guinea pig. Concentrations of 17 cardenolides, cardenolide glucuronides and sulfates producing half-maximal inhibition of (Na+, K+)-membrane-ATPase from different organs and animal species were determined in vitro. In addition the concentrations that increased the contractility of guinea pig isolated papillary muscles to a particular level were investigated. Comparisons between ATPase-inhibiting and positive inotropic cardiac activities showed extensive parallelism: the correlation coefficients after log/log transformation were between 0.92 and 0.97. The same close correlations are found if dissociation constants of cardenolide receptor complexes and concentrations causing 86Rb-uptake inhibition in human erythrocytes are examined. The concentrations necessary for inhibition of (Na+, K+)-membrane-ATPase of the guinea pig heart and the concentrations required to achieve a defined positive inotropic effect in guinea pig papillary muscle showed a log/log correlation coefficient of 0.97 (P less than 0.001). In both tests the potencies covered more than three orders of magnitude. The results support Repke's hypothesis on the digitalis receptor."}
{"id": "PMID:211448", "title": "Kainic acid-induced lesion of dopaminergic target cells in the striatum: consequences on the dynamics of cerebellar cGMP.", "content": "The bilateral intrastriatal injection of kainic acid (2 microgram/caudate) caused a marked decrease in the activity of striatal dopamine-sensitive adenylate cyclase. This probable loss of target cells for dopamine was associated with a parallel decrease of the cGMP level in the cerebellar cortex, which was maximal (80% loss) by 24 h and prevented apomorphine from raising cerebellar cGMP levels. On the contrary harmaline and isoniazid both increased the levels of cerebellar cGMP in kainic-lesioned rats to the same extent as in control rats. The results indicate that dopamine mechanisms in the striatum are involved in the regulation of cerebellar cortex cGMP.", "contents": "Kainic acid-induced lesion of dopaminergic target cells in the striatum: consequences on the dynamics of cerebellar cGMP. The bilateral intrastriatal injection of kainic acid (2 microgram/caudate) caused a marked decrease in the activity of striatal dopamine-sensitive adenylate cyclase. This probable loss of target cells for dopamine was associated with a parallel decrease of the cGMP level in the cerebellar cortex, which was maximal (80% loss) by 24 h and prevented apomorphine from raising cerebellar cGMP levels. On the contrary harmaline and isoniazid both increased the levels of cerebellar cGMP in kainic-lesioned rats to the same extent as in control rats. The results indicate that dopamine mechanisms in the striatum are involved in the regulation of cerebellar cortex cGMP."}
{"id": "PMID:211453", "title": "[Neurological complications of Argentinian hemorrhagic fever].", "content": "The Argentine hemorrhagic fever (AHF) is an infectious disease, endemo-epidemical, of viral etiology, produced by the Junin virus and limited to the Buenos Aires Province, South of C\u00f3rdoba, East of La Pampa, and South of Santa Fe. It generally assails rural workers at harvest-time, especially during corn-harvest. The incubation period of the disease does not exceed 12 days. A feverish syndrome with asthenia, adynamia, myalgias, migraine, photophobia, epigastralgia etc., appear. The patient has a facial erythema, petechias on the skin, enantema on the palate, conjunctive micropolyadenopaty injection. The laboratory shows a low erytro, leukopenia with aneosinophilia, thrombopenia and a urine with albuminuria and virous cells. After the fourth day, hemorrhage and a neurological case appears. The laboratory tends to normalize and cast appears in the urine. The most striking neurological signs are the following: muscular hypotonia, proprioceptive hyporreflexia or arreflexia, marinesco reflex, shakings, difficulty to stand and walk, oscillations in consciousness level, and ocular disturbances. The cytochemical test of the C.L. Rachis in the usual ways of the AHF is within its normal characteristics; on the other hand there are modifications in the nervous cases: the total proteins are nearly always increased and the cells augmented with a great predominance of mononuclear cells. The electroencephalogrammes were always abnormal, varying from a brief disorganization up to a diffusive and permanent slowness. The half of which additionally presented paroxisms generalized by slow waves. The pathological anatomy over  the central nervous system makes us think that the lesion would not primitively neuronal but that the action of the virus would be indirectly done through the capillar wall. This capillar lesion is produced by multiple focuses. The neuronal destruction with necrosis by microinfarcts is minimum. The symptoms and neurological signs are present in 10% of the clinical cases; the death-rate in the nervous clinical cases having reached 50% of them. The premature treatment allows the death-rate to diminish and the cases that survive have not many after effects.", "contents": "[Neurological complications of Argentinian hemorrhagic fever]. The Argentine hemorrhagic fever (AHF) is an infectious disease, endemo-epidemical, of viral etiology, produced by the Junin virus and limited to the Buenos Aires Province, South of C\u00f3rdoba, East of La Pampa, and South of Santa Fe. It generally assails rural workers at harvest-time, especially during corn-harvest. The incubation period of the disease does not exceed 12 days. A feverish syndrome with asthenia, adynamia, myalgias, migraine, photophobia, epigastralgia etc., appear. The patient has a facial erythema, petechias on the skin, enantema on the palate, conjunctive micropolyadenopaty injection. The laboratory shows a low erytro, leukopenia with aneosinophilia, thrombopenia and a urine with albuminuria and virous cells. After the fourth day, hemorrhage and a neurological case appears. The laboratory tends to normalize and cast appears in the urine. The most striking neurological signs are the following: muscular hypotonia, proprioceptive hyporreflexia or arreflexia, marinesco reflex, shakings, difficulty to stand and walk, oscillations in consciousness level, and ocular disturbances. The cytochemical test of the C.L. Rachis in the usual ways of the AHF is within its normal characteristics; on the other hand there are modifications in the nervous cases: the total proteins are nearly always increased and the cells augmented with a great predominance of mononuclear cells. The electroencephalogrammes were always abnormal, varying from a brief disorganization up to a diffusive and permanent slowness. The half of which additionally presented paroxisms generalized by slow waves. The pathological anatomy over  the central nervous system makes us think that the lesion would not primitively neuronal but that the action of the virus would be indirectly done through the capillar wall. This capillar lesion is produced by multiple focuses. The neuronal destruction with necrosis by microinfarcts is minimum. The symptoms and neurological signs are present in 10% of the clinical cases; the death-rate in the nervous clinical cases having reached 50% of them. The premature treatment allows the death-rate to diminish and the cases that survive have not many after effects."}
{"id": "PMID:211454", "title": "[Virological studies in acute polyradiculoneuritis, LGBS type. Various findings in relation to Coxsackie A4 virus].", "content": "Studies of isolated virus in LCR and necropsy material were made (medulla roots and rachi ganglia) in acute cases of polyradiculoneuritis. Landry-Gullain-Barr\u00e9-Strohl type. Serological studies with prepared sera were also made (at three week intervals). The results were discussed based on the isolation of a Coxsackie A virus in four cases and the corresponding serological findings.", "contents": "[Virological studies in acute polyradiculoneuritis, LGBS type. Various findings in relation to Coxsackie A4 virus]. Studies of isolated virus in LCR and necropsy material were made (medulla roots and rachi ganglia) in acute cases of polyradiculoneuritis. Landry-Gullain-Barr\u00e9-Strohl type. Serological studies with prepared sera were also made (at three week intervals). The results were discussed based on the isolation of a Coxsackie A virus in four cases and the corresponding serological findings."}
{"id": "PMID:211455", "title": "Hormonal response to stress in the squirrel monkey (Saimiri sciureus).", "content": "The pituitary-adrenal and gonadal responses following stress were evaluated in the squirrel monkey. Plasma levels of cortisol (CS), ACTH and testosterone (T) were determined during a 4-h period following the combined stress of capture and ether anesthesia. The results indicated that the squirrel monkey manifests higher basal levels of steroids than typically found in other mammals. The endocrine response following stress was biphasic, involving an initial elevation and subsequent decline in hormone levels. Males manifested significantly higher plasma levels of CS and T and lower plasma levels of ACTH than did females.", "contents": "Hormonal response to stress in the squirrel monkey (Saimiri sciureus). The pituitary-adrenal and gonadal responses following stress were evaluated in the squirrel monkey. Plasma levels of cortisol (CS), ACTH and testosterone (T) were determined during a 4-h period following the combined stress of capture and ether anesthesia. The results indicated that the squirrel monkey manifests higher basal levels of steroids than typically found in other mammals. The endocrine response following stress was biphasic, involving an initial elevation and subsequent decline in hormone levels. Males manifested significantly higher plasma levels of CS and T and lower plasma levels of ACTH than did females."}
{"id": "PMID:211464", "title": "Uptake and release of norepinephrine by slices of rat cerebral cortex: effect of agents that increase cyclic AMP levels.", "content": "Cerebral cortical slices from rats were incubated in physiologic saline, and the uptake, release, and K+-stimulated release of norepinephrine were measured. Dibutyryl cyclic AMP, the phosphodiesterase inhibitors aminophylline and papaverine, and adenosine (which stimulates adenyl cyclase) all caused a variable increase in uptake of norepinephrine at concentrations ranging from 10(-7) to 10(-4) M. Prostaglandins E1 and E2 appeared to have no effect on uptake, but this may be because the alcohol required to dissolve them had an inhibitory effect on uptake. None of these compounds appeared to affect basal or K+-stimulated release of norepinephrine. These agents therefore seem to have an effect opposite to that of the tricyclic antidepressants (which inhibit uptake of norepinephrine). Since norepinephrine's postsynaptic effects are usually inhibitory in the cortex, the stimulatory effect of the drugs tested on the presynaptic uptake of norepinephrine may explain the stimulant and epileptogenic effects of these drugs.", "contents": "Uptake and release of norepinephrine by slices of rat cerebral cortex: effect of agents that increase cyclic AMP levels. Cerebral cortical slices from rats were incubated in physiologic saline, and the uptake, release, and K+-stimulated release of norepinephrine were measured. Dibutyryl cyclic AMP, the phosphodiesterase inhibitors aminophylline and papaverine, and adenosine (which stimulates adenyl cyclase) all caused a variable increase in uptake of norepinephrine at concentrations ranging from 10(-7) to 10(-4) M. Prostaglandins E1 and E2 appeared to have no effect on uptake, but this may be because the alcohol required to dissolve them had an inhibitory effect on uptake. None of these compounds appeared to affect basal or K+-stimulated release of norepinephrine. These agents therefore seem to have an effect opposite to that of the tricyclic antidepressants (which inhibit uptake of norepinephrine). Since norepinephrine's postsynaptic effects are usually inhibitory in the cortex, the stimulatory effect of the drugs tested on the presynaptic uptake of norepinephrine may explain the stimulant and epileptogenic effects of these drugs."}
{"id": "PMID:211465", "title": "Diagnostic significance of myeloperoxidase assay in neuronal ceroid-lipofuscinoses (Batten-Vogt syndrome).", "content": "In 13 patients with morphologically established juvenile neuronal ceroid lipofuscinosis and 13 controls, the activity of leukocyte peroxidase (myeloperoxidase) was determined under various conditions: Measurement of water-soluble enzyme, the buffer-soluble enzyme, and the leukocyte homogenate; application of phosphate buffer (pH7.0) and borate buffer (pH7.6); employment of 9mM, 28mM, and 55mMp-phenylenediamine as hydrogen donor; and measurement of the specific enzyme extinction at 10, 60, and 180 seconds. A significant difference between mean values for patients and controls could not be established. In both groups, single individuals exhibited definitely increased or reduced enzyme concentrations, leaving us, however, without an adequate explanation for these observations. Our studies indicate that determination of myeloperoxidase has no value in establishing the diagnosis of neuronal ceroid-lipofuscinoses.", "contents": "Diagnostic significance of myeloperoxidase assay in neuronal ceroid-lipofuscinoses (Batten-Vogt syndrome). In 13 patients with morphologically established juvenile neuronal ceroid lipofuscinosis and 13 controls, the activity of leukocyte peroxidase (myeloperoxidase) was determined under various conditions: Measurement of water-soluble enzyme, the buffer-soluble enzyme, and the leukocyte homogenate; application of phosphate buffer (pH7.0) and borate buffer (pH7.6); employment of 9mM, 28mM, and 55mMp-phenylenediamine as hydrogen donor; and measurement of the specific enzyme extinction at 10, 60, and 180 seconds. A significant difference between mean values for patients and controls could not be established. In both groups, single individuals exhibited definitely increased or reduced enzyme concentrations, leaving us, however, without an adequate explanation for these observations. Our studies indicate that determination of myeloperoxidase has no value in establishing the diagnosis of neuronal ceroid-lipofuscinoses."}
{"id": "PMID:211461", "title": "Unit activity in the cat visual cortex in the sleep--waking cycle.", "content": "Changes in spontaneous unit activity in the primary visual cortex during the sleep-waking cycle were studied in chronic experiments on dark-adapted cats. In the cell poulation studied activity in states of wakefulness and of paradoxical sleep did not differ significantly either in mean discharge frequency or in pattern. Activity of most cells in a state of slow sleep differed significantly from that in states of wakefulness and paradoxical sleep by the development of a \"burst-pause\" pattern in the unit discharges.", "contents": "Unit activity in the cat visual cortex in the sleep--waking cycle. Changes in spontaneous unit activity in the primary visual cortex during the sleep-waking cycle were studied in chronic experiments on dark-adapted cats. In the cell poulation studied activity in states of wakefulness and of paradoxical sleep did not differ significantly either in mean discharge frequency or in pattern. Activity of most cells in a state of slow sleep differed significantly from that in states of wakefulness and paradoxical sleep by the development of a \"burst-pause\" pattern in the unit discharges."}
{"id": "PMID:211468", "title": "Corneal ultrastructural changes in Fabry's disease.", "content": "A case of Fabry's disease is reported. The findings of the corneal alterations with the light microscope as well as with the electron microscope are described. The diffuse corneal haziness seems to be due to small intracellular osmiophilic inclusions of the epithelium. There seems also to be a relation between the giant inclusions in the corneal epithelium, not yet described, and the clinical presence of punctiform grey opacities. The pathogenesis of the whorl-like opacities remains unsolved.", "contents": "Corneal ultrastructural changes in Fabry's disease. A case of Fabry's disease is reported. The findings of the corneal alterations with the light microscope as well as with the electron microscope are described. The diffuse corneal haziness seems to be due to small intracellular osmiophilic inclusions of the epithelium. There seems also to be a relation between the giant inclusions in the corneal epithelium, not yet described, and the clinical presence of punctiform grey opacities. The pathogenesis of the whorl-like opacities remains unsolved."}
{"id": "PMID:211469", "title": "Clinical, genetic, and histologic features of the trichoonychodental (TOD) syndrome.", "content": "A syndrome of scanty, fine, curled hair, thin dysplastic nails, taurodontic molars, hypoplastic-hypomature enamel, dysplasia of dentin, and hypohidrosis segregating as an autosomal dominant trait is described in a Japanese family. The patients received repeated doses of tetracycline during odontogenesis which fortuitously assisted in interpreting the pathogenesis of the dentin defect. The condition was previously described as familial congenital ectodermal dysplasia by Westerholm and as odontogenesis imperfecta by Siiril\u00e4 and Heikinheimo. It is suggested that the name trichoonychodental (TOD) syndrome is a better descriptive term for the condition.", "contents": "Clinical, genetic, and histologic features of the trichoonychodental (TOD) syndrome. A syndrome of scanty, fine, curled hair, thin dysplastic nails, taurodontic molars, hypoplastic-hypomature enamel, dysplasia of dentin, and hypohidrosis segregating as an autosomal dominant trait is described in a Japanese family. The patients received repeated doses of tetracycline during odontogenesis which fortuitously assisted in interpreting the pathogenesis of the dentin defect. The condition was previously described as familial congenital ectodermal dysplasia by Westerholm and as odontogenesis imperfecta by Siiril\u00e4 and Heikinheimo. It is suggested that the name trichoonychodental (TOD) syndrome is a better descriptive term for the condition."}
{"id": "PMID:211475", "title": "Glycoproteins from the aorta.", "content": "This review deals with the data on isolation techniques, structure, physicochemical properties and biological function of glycoproteins isolated from the aorta. Some glycoproteins extracted at low ionic strengths (soluble glycoproteins) are immunologically distinct from serum glycoproteins. The designation \"structural glycoprotein\" was proposed for glycoproteins associated with the collagen elastin matrix. These glycoproteins are solubilized by dissociative and reducing buffers. A selective hydrolysis of the insoluble collagen prior to their extraction was also reported. The molecular weights are in the range of 53 - 72.000 and 35.000 - 27.000 daltons for the soluble and the structural glycoproteins respectively. The aorta glycoproteins are rich in polar aminoacids. The primary structure of glycoproteins from aorta is not yet established. The electrophoretic mobility and sugar content of some glycoproteins extracted at low ionic forces change with the maturation and sex. The biosynthesis of a soluble glycoprotein (glycoprotein B) and of structural glycoproteins by aortic smooth muscle cells was demonstrated \"in vitro\". The structural glycoproteins appear as microfibrillae in electron microscopy. Their self-aggregation may be due to hydrophobic interactions. The association of microfibrillar glycoprotein with elastin in connective tissues and in the culture medium of aortic smooth muscle cells suggests the role of glycoprotein-elastin interactions in morphogenesis.", "contents": "Glycoproteins from the aorta. This review deals with the data on isolation techniques, structure, physicochemical properties and biological function of glycoproteins isolated from the aorta. Some glycoproteins extracted at low ionic strengths (soluble glycoproteins) are immunologically distinct from serum glycoproteins. The designation \"structural glycoprotein\" was proposed for glycoproteins associated with the collagen elastin matrix. These glycoproteins are solubilized by dissociative and reducing buffers. A selective hydrolysis of the insoluble collagen prior to their extraction was also reported. The molecular weights are in the range of 53 - 72.000 and 35.000 - 27.000 daltons for the soluble and the structural glycoproteins respectively. The aorta glycoproteins are rich in polar aminoacids. The primary structure of glycoproteins from aorta is not yet established. The electrophoretic mobility and sugar content of some glycoproteins extracted at low ionic forces change with the maturation and sex. The biosynthesis of a soluble glycoprotein (glycoprotein B) and of structural glycoproteins by aortic smooth muscle cells was demonstrated \"in vitro\". The structural glycoproteins appear as microfibrillae in electron microscopy. Their self-aggregation may be due to hydrophobic interactions. The association of microfibrillar glycoprotein with elastin in connective tissues and in the culture medium of aortic smooth muscle cells suggests the role of glycoprotein-elastin interactions in morphogenesis."}
{"id": "PMID:211477", "title": "[Circadian rhythms in man. Their incidence in endocrinology (author's transl)].", "content": "The authors, after a classification of the main biological rhythms, mention the parameters of the circadian rhythm deduced by mathematical analysis of so-called \"Cosinor\". They then devote their study to the main hormones, the secretion of which depends on circadian periodicity. They emphasize the effect that their biorhythm has on the value of plasma concentrations depending on the time of sampling. They suggest standardisation of this time in drawing up international norms.", "contents": "[Circadian rhythms in man. Their incidence in endocrinology (author's transl)]. The authors, after a classification of the main biological rhythms, mention the parameters of the circadian rhythm deduced by mathematical analysis of so-called \"Cosinor\". They then devote their study to the main hormones, the secretion of which depends on circadian periodicity. They emphasize the effect that their biorhythm has on the value of plasma concentrations depending on the time of sampling. They suggest standardisation of this time in drawing up international norms."}
{"id": "PMID:211483", "title": "Technique for measurement of inert gases in liquids by gas chromatography.", "content": "A method for quantitative analysis of inert gases in liquids by gas chromatography is described. The technique comprises an equilibration system for partial extraction of dissolved gases from liquids and a gas chromatograph equipped with helium ionization detector. The method is particularly devised for determination of solubility coefficients of gases in liquid materials, e.g. water, aqueous solutions, blood, tissue homogenates, and for simultaneous measurement of several inert gases dissolved in liquids. Coefficients of variation for serial analyses of individual samples were less than or equal to 3%. The method is applicable to studies of blood-tissue transfer of respiratory and inert gases.", "contents": "Technique for measurement of inert gases in liquids by gas chromatography. A method for quantitative analysis of inert gases in liquids by gas chromatography is described. The technique comprises an equilibration system for partial extraction of dissolved gases from liquids and a gas chromatograph equipped with helium ionization detector. The method is particularly devised for determination of solubility coefficients of gases in liquid materials, e.g. water, aqueous solutions, blood, tissue homogenates, and for simultaneous measurement of several inert gases dissolved in liquids. Coefficients of variation for serial analyses of individual samples were less than or equal to 3%. The method is applicable to studies of blood-tissue transfer of respiratory and inert gases."}
{"id": "PMID:211485", "title": "A nuclear protein-modifying enzyme is responsive to ordered chromatin structure.", "content": "Poly (ADP-ribose) polymerase, a nuclear protein-modifying enzyme, binds to the internucleosomal linker region of chromatin, although it modifies certain core nucleosomal histones in addition to histone H1. The activity per unit of DNA chromatin changes with the nucleosome repeat number. It reaches a maximum on chromatin of 8-10 nucleosomes in length. As the complexity of chromatin with respect to nucleosome repeat number and compactness increases, a decline and stabilization of specific activity is noted. The difference in specific activity is maintained through resedimentation and dialysis of particles. It does not appear due to differences in polymer chain length or differential degradation of poly (ADP-ribose). The data suggest a relationship between ADP-ribosylation and chromatin organization and vice versa.", "contents": "A nuclear protein-modifying enzyme is responsive to ordered chromatin structure. Poly (ADP-ribose) polymerase, a nuclear protein-modifying enzyme, binds to the internucleosomal linker region of chromatin, although it modifies certain core nucleosomal histones in addition to histone H1. The activity per unit of DNA chromatin changes with the nucleosome repeat number. It reaches a maximum on chromatin of 8-10 nucleosomes in length. As the complexity of chromatin with respect to nucleosome repeat number and compactness increases, a decline and stabilization of specific activity is noted. The difference in specific activity is maintained through resedimentation and dialysis of particles. It does not appear due to differences in polymer chain length or differential degradation of poly (ADP-ribose). The data suggest a relationship between ADP-ribosylation and chromatin organization and vice versa."}
{"id": "PMID:211486", "title": "An electron microscopic method for the mapping of proteins attached to nucleic acids.", "content": "An electron microscopic method for demonstrating the presence of and mapping the positions of proteins specifically bound to nucleic acids is described. The nucleic acid-protein complex is treated with dinitrofluorobenzene under conditions such that dinitrophenyl (DNP) groups are attached to nucleophilic groups on the protein, with only a low level of random attachment to the nuclei acid. This product is treated with rabbit anti-DNP IgG. The position of the protein-(DNP)n(IgG)m complex on the nucleic acid strand can be observed by electron microscopy by protein free spreading methods and, in many cases, by cytochrome-c spreading. If necessary for visualization by the latter method, the size of the labeled region can be increased by treatment with goat anti-rabbit IgG. High efficiency of electron microscopic labeling is achieved. Examples studied are: the adenovirus-2 DNA terminal protein, a protein covalently bound to SV40 DNA, DNA polymerase I bound to DNA, E. coli RNA polymerase bound to T7 DNA, and proteins UV crosslinked to avian sarcoma virus RNA.", "contents": "An electron microscopic method for the mapping of proteins attached to nucleic acids. An electron microscopic method for demonstrating the presence of and mapping the positions of proteins specifically bound to nucleic acids is described. The nucleic acid-protein complex is treated with dinitrofluorobenzene under conditions such that dinitrophenyl (DNP) groups are attached to nucleophilic groups on the protein, with only a low level of random attachment to the nuclei acid. This product is treated with rabbit anti-DNP IgG. The position of the protein-(DNP)n(IgG)m complex on the nucleic acid strand can be observed by electron microscopy by protein free spreading methods and, in many cases, by cytochrome-c spreading. If necessary for visualization by the latter method, the size of the labeled region can be increased by treatment with goat anti-rabbit IgG. High efficiency of electron microscopic labeling is achieved. Examples studied are: the adenovirus-2 DNA terminal protein, a protein covalently bound to SV40 DNA, DNA polymerase I bound to DNA, E. coli RNA polymerase bound to T7 DNA, and proteins UV crosslinked to avian sarcoma virus RNA."}
{"id": "PMID:211484", "title": "Fused rocket and rocket immunoelectrophoresis adapted for demonstration and quantitation of the A antigen of Marek's disease virus-infected cell cultures.", "content": "Preliminary results have shown that the rocket immunoelectrophoresis technique can be used as a method for quantitation of the A antigen of Marek's Disease virus-infected cell cultures.", "contents": "Fused rocket and rocket immunoelectrophoresis adapted for demonstration and quantitation of the A antigen of Marek's disease virus-infected cell cultures. Preliminary results have shown that the rocket immunoelectrophoresis technique can be used as a method for quantitation of the A antigen of Marek's Disease virus-infected cell cultures."}
{"id": "PMID:211487", "title": "Chromosome of the mature virion of simian virus 40 contains H1 histone.", "content": "In addition to free SV40 minichromosomes in the compact form, complete virions were obtained from the nuclear extract of productively infected cells. Capsid proteins VP1, VP2, and VP3, as well as histones, were observed on  electrophoregrams of proteins prepared from virions. In contrast to the widely accepted view, histone H1 was found in virions in stoichiometric amounts with respect to other histones. The same is true for virions isolated by a conventional method. Free minichromosomes present in infected cells contain all histones and practically no viral proteins.", "contents": "Chromosome of the mature virion of simian virus 40 contains H1 histone. In addition to free SV40 minichromosomes in the compact form, complete virions were obtained from the nuclear extract of productively infected cells. Capsid proteins VP1, VP2, and VP3, as well as histones, were observed on  electrophoregrams of proteins prepared from virions. In contrast to the widely accepted view, histone H1 was found in virions in stoichiometric amounts with respect to other histones. The same is true for virions isolated by a conventional method. Free minichromosomes present in infected cells contain all histones and practically no viral proteins."}
{"id": "PMID:211488", "title": "Purification of a DNA nicking-closing enzyme from mouse L cells.", "content": "A DNA nicking-closing enzyme has been purified from the nuclei of mouse L cells to 90% homogeneity. The denatured and reduced form of the enzyme has a molecular weight of 68,000 which is in agreement with the molecular weight of the native enzyme as determined by gel filtration and by sucrose sedimentation velocity assuming the protein is globular. Therefore, the active form of the enzyme is a monopolypeptide. Its isoelectric point is pH 4.2 +/- 0.2. The nicking-closing activity does not require a cofactor and does not involve any sulfhydryl group. The enzyme requires 0.2 M NaCl and pH in the range of 6.5-7.5 for optimal activity.", "contents": "Purification of a DNA nicking-closing enzyme from mouse L cells. A DNA nicking-closing enzyme has been purified from the nuclei of mouse L cells to 90% homogeneity. The denatured and reduced form of the enzyme has a molecular weight of 68,000 which is in agreement with the molecular weight of the native enzyme as determined by gel filtration and by sucrose sedimentation velocity assuming the protein is globular. Therefore, the active form of the enzyme is a monopolypeptide. Its isoelectric point is pH 4.2 +/- 0.2. The nicking-closing activity does not require a cofactor and does not involve any sulfhydryl group. The enzyme requires 0.2 M NaCl and pH in the range of 6.5-7.5 for optimal activity."}
{"id": "PMID:211489", "title": "The relationship of SV40 replicating chromosomes to two forms of the non-replicating SV40.", "content": "SV40 replicating chromosomes were extracted from infected cells using a detergent free extraction method. This procedure also extracts 2 forms of the non-replicating chromosome, one of which corresponds to the well characterized 50-55S SV40 minichromosome. The other is a more compact structure which has a sedimentation coefficient of 80-85S. The replicating chromosomes sediment between the 2 conformations of the mature chromosome. Electron microscopy of the replicating chromosomes suggests an overall conformation that resembles the 50-55S form of the mature chromosome rather than that of the 80-85S structure. Nucleosomes are present on both sides of the replication forks. When the replicating chromosomes were incubated in an in vitro DNA synthesis assay all regions of the SV40 genome were synthesized and a significant fraction of the replicating chromosomes completed replication. The progeny chromosomes co-sedimented with the 50-55S chromosomes which were present prior to the incubation. The sedimentation coefficients and relative amounts of the two forms of the mature chromosome were unaffected by the incubation.", "contents": "The relationship of SV40 replicating chromosomes to two forms of the non-replicating SV40. SV40 replicating chromosomes were extracted from infected cells using a detergent free extraction method. This procedure also extracts 2 forms of the non-replicating chromosome, one of which corresponds to the well characterized 50-55S SV40 minichromosome. The other is a more compact structure which has a sedimentation coefficient of 80-85S. The replicating chromosomes sediment between the 2 conformations of the mature chromosome. Electron microscopy of the replicating chromosomes suggests an overall conformation that resembles the 50-55S form of the mature chromosome rather than that of the 80-85S structure. Nucleosomes are present on both sides of the replication forks. When the replicating chromosomes were incubated in an in vitro DNA synthesis assay all regions of the SV40 genome were synthesized and a significant fraction of the replicating chromosomes completed replication. The progeny chromosomes co-sedimented with the 50-55S chromosomes which were present prior to the incubation. The sedimentation coefficients and relative amounts of the two forms of the mature chromosome were unaffected by the incubation."}
{"id": "PMID:211490", "title": "Chemical synthesis of 5'-pyrophosphate and triphosphate derivatives of 3'-5' ApA, ApG, GpA and GpG. CD study of the effect of 5'-phosphate groups on the conformation of 3'-5' GpG.", "content": "A simple, two-step method is described for the synthesis of the 5'-pyro- and triphosphate derivatives of 3'-5' ApA, ApG, GpA and GpG. The readily accessible 2'(3')-5' ApA, ApG, GpA and GpG were converted in one step to the corresponding 5'-phosphoramidate derivatives which were then transformed to the 5'-pyro- and triphosphates. CD spectra of 3'-5' pn GpG (n = 0,1,2 or 3) derivatives, measured at pH 1, indicated stabilization of the (syn) G+p (anti)G conformation by the 5'-phosphate groups.", "contents": "Chemical synthesis of 5'-pyrophosphate and triphosphate derivatives of 3'-5' ApA, ApG, GpA and GpG. CD study of the effect of 5'-phosphate groups on the conformation of 3'-5' GpG. A simple, two-step method is described for the synthesis of the 5'-pyro- and triphosphate derivatives of 3'-5' ApA, ApG, GpA and GpG. The readily accessible 2'(3')-5' ApA, ApG, GpA and GpG were converted in one step to the corresponding 5'-phosphoramidate derivatives which were then transformed to the 5'-pyro- and triphosphates. CD spectra of 3'-5' pn GpG (n = 0,1,2 or 3) derivatives, measured at pH 1, indicated stabilization of the (syn) G+p (anti)G conformation by the 5'-phosphate groups."}
{"id": "PMID:211491", "title": "Inhibition of tRNA methylation in vitro and in whole cells by an oncostatic S-adenosyl-homocysteine (SAH) analogue: 5'-deoxy 5'-S-isobutyl adenosine (SIBA).", "content": "A high increase in the amount of methylated tRNA bases was found in vivo in Rous sarcoma virus infected and transformed chick embryo fibroblasts in comparison with normal cells, tRNA methylases extracted from transformed cells showed also higher activity in vitro with a heterologous substrate. 5'-deoxy-5'-S-isobutyl adenosine, (a structural analogue of S-adenosyl-L homocysteine), which inhibits virus-induced cell transformation, inhibits also the increase of incorporation of labelled methyl groups into tRNA in infected and transformed cells. When normal cells are grown in the presence of this inhibitor, undermethylated tRNAs are obtained. The effect of the drug is different in normal, infected and transformed cells. The methylation of the different bases is inhibited in vitro and in vivo to various extent. The effect of this substance on tRNA methylation may be the cause of its inhibitory effect on cell transformation.", "contents": "Inhibition of tRNA methylation in vitro and in whole cells by an oncostatic S-adenosyl-homocysteine (SAH) analogue: 5'-deoxy 5'-S-isobutyl adenosine (SIBA). A high increase in the amount of methylated tRNA bases was found in vivo in Rous sarcoma virus infected and transformed chick embryo fibroblasts in comparison with normal cells, tRNA methylases extracted from transformed cells showed also higher activity in vitro with a heterologous substrate. 5'-deoxy-5'-S-isobutyl adenosine, (a structural analogue of S-adenosyl-L homocysteine), which inhibits virus-induced cell transformation, inhibits also the increase of incorporation of labelled methyl groups into tRNA in infected and transformed cells. When normal cells are grown in the presence of this inhibitor, undermethylated tRNAs are obtained. The effect of the drug is different in normal, infected and transformed cells. The methylation of the different bases is inhibited in vitro and in vivo to various extent. The effect of this substance on tRNA methylation may be the cause of its inhibitory effect on cell transformation."}
{"id": "PMID:211492", "title": "Substrate dependence of the mechanism of EcoRI endonuclease.", "content": "The mechanism of EcoRI endonuclease is substrate dependent. At 37 degrees dissociation of the enzyme-Form II DNA intermediates of ColE1 DNA and bacteriophage G4 RFI DNA is negligible. Therefore, both DNA strands with in the EcoRI sequence are cleaved during a single binding event. However, double strand cleavage of SV40 DNA occurs without dissociation of the enzyme in only 75% of the catalytic events. This mechanistic difference presumably reflects sequence differences about the EcoRI sites of these DNA's.", "contents": "Substrate dependence of the mechanism of EcoRI endonuclease. The mechanism of EcoRI endonuclease is substrate dependent. At 37 degrees dissociation of the enzyme-Form II DNA intermediates of ColE1 DNA and bacteriophage G4 RFI DNA is negligible. Therefore, both DNA strands with in the EcoRI sequence are cleaved during a single binding event. However, double strand cleavage of SV40 DNA occurs without dissociation of the enzyme in only 75% of the catalytic events. This mechanistic difference presumably reflects sequence differences about the EcoRI sites of these DNA's."}
{"id": "PMID:211498", "title": "[Examinations to cAMP-levels in plasma (author's transl)].", "content": "Plasma cAMP levels were measured by a competetive protein binding method in nine healthy volunteers every 30 minutes over a period of 24 hours under standardized conditions. No circadian variation was observed. Upright posture after 32 hours bedrest increased cAMP significantly.", "contents": "[Examinations to cAMP-levels in plasma (author's transl)]. Plasma cAMP levels were measured by a competetive protein binding method in nine healthy volunteers every 30 minutes over a period of 24 hours under standardized conditions. No circadian variation was observed. Upright posture after 32 hours bedrest increased cAMP significantly."}
{"id": "PMID:211501", "title": "Intestinal giardiasis, steatorrhoea and peripheral nerve dysfunction.", "content": "Two patients presented with similar peripheral neuropathic symptoms. Muscle denervation was shown by electromyography and muscle biopsy. Motor and sensory nerve conduction studies were normal. Both patients had intestinal giardiasis: 1 had asymptomatic steatorrhoea, and the other had diarrhoea and abdominal pain. Treatment with metronidazole abolished the gastrointestinal symptoms. After a delay of several months the neurological symptoms also gradually improved. No other cause of peripheral neuropathy was apparent on investigation, and the relationship between the intestinal giardiasis and the peripheral neuropathy is discussed.", "contents": "Intestinal giardiasis, steatorrhoea and peripheral nerve dysfunction. Two patients presented with similar peripheral neuropathic symptoms. Muscle denervation was shown by electromyography and muscle biopsy. Motor and sensory nerve conduction studies were normal. Both patients had intestinal giardiasis: 1 had asymptomatic steatorrhoea, and the other had diarrhoea and abdominal pain. Treatment with metronidazole abolished the gastrointestinal symptoms. After a delay of several months the neurological symptoms also gradually improved. No other cause of peripheral neuropathy was apparent on investigation, and the relationship between the intestinal giardiasis and the peripheral neuropathy is discussed."}
{"id": "PMID:211502", "title": "Isolation of an avian erythrocyte protein possessing ADP-ribosyltransferase activity and capable of activating adenylate cyclase.", "content": "An ADP-ribosyltransferase was purified approximately 500-fold from the supernatant fraction of turkey erythrocytes. The enzyme hydrolyzed [carbonyl-(14)C]NAD to ADP-ribose and [carbonyl-(14)C]nicotinamide at a low rate. Nicotinamide formation from NAD was enhanced by arginine methyl ester > D-arginine approximately L-arginine > guanidine; lysine, histidine, and citrulline were ineffective. Incubation of [adenine-U-(14)C]NAD and arginine methyl ester or arginine with the purified enzyme resulted in the formation of new compounds that contained (14)C, reacted with ninhydrin, and quenched background fluorescence of thin-layer plates viewed in ultraviolet light. Their mobilities on thin-layer chromatograms were indistinguishable from those of ADP-ribosylarginine methyl ester and ADP-ribosylarginine formed during incubation of choleragen with NAD and arginine methyl ester or arginine, respectively [Moss, J. & Vaughan, M. (1977) J. Biol. Chem. 252, 2455-2457]. The purified transferase also catalyzed the incorporation of label from [adenine-(14)C]-NAD into lysozyme, histones and polyarginine. When the (14)C-labeled lysozyme was incubated with snake venom phosphodiesterase, the radioactivity was released and, on thin-layer chromatograms, exhibited a mobility indistinguishable from that of 5'-AMP, as would be expected of an ADP-ribosylated protein, but not of a poly(ADP-ribosylated) product. The purified transferase activated rat brain adenylate cyclase and, as is the case with choleragen, activation was absolutely dependent on NAD. The presence in the avian erythrocyte of a protein that, like choleragen and Escherichia coli heat-labile enterotoxin, apparently activates adenylate cyclase and possesses ADP-ribosyl transferase activity is consistent with the view that the mechanisms through which the bacterial toxins produce pathology are not entirely foreign to vertebrate cells, at least some of which may possess and employ an analogous mechanism for activation of adenylate cyclase.", "contents": "Isolation of an avian erythrocyte protein possessing ADP-ribosyltransferase activity and capable of activating adenylate cyclase. An ADP-ribosyltransferase was purified approximately 500-fold from the supernatant fraction of turkey erythrocytes. The enzyme hydrolyzed [carbonyl-(14)C]NAD to ADP-ribose and [carbonyl-(14)C]nicotinamide at a low rate. Nicotinamide formation from NAD was enhanced by arginine methyl ester > D-arginine approximately L-arginine > guanidine; lysine, histidine, and citrulline were ineffective. Incubation of [adenine-U-(14)C]NAD and arginine methyl ester or arginine with the purified enzyme resulted in the formation of new compounds that contained (14)C, reacted with ninhydrin, and quenched background fluorescence of thin-layer plates viewed in ultraviolet light. Their mobilities on thin-layer chromatograms were indistinguishable from those of ADP-ribosylarginine methyl ester and ADP-ribosylarginine formed during incubation of choleragen with NAD and arginine methyl ester or arginine, respectively [Moss, J. & Vaughan, M. (1977) J. Biol. Chem. 252, 2455-2457]. The purified transferase also catalyzed the incorporation of label from [adenine-(14)C]-NAD into lysozyme, histones and polyarginine. When the (14)C-labeled lysozyme was incubated with snake venom phosphodiesterase, the radioactivity was released and, on thin-layer chromatograms, exhibited a mobility indistinguishable from that of 5'-AMP, as would be expected of an ADP-ribosylated protein, but not of a poly(ADP-ribosylated) product. The purified transferase activated rat brain adenylate cyclase and, as is the case with choleragen, activation was absolutely dependent on NAD. The presence in the avian erythrocyte of a protein that, like choleragen and Escherichia coli heat-labile enterotoxin, apparently activates adenylate cyclase and possesses ADP-ribosyl transferase activity is consistent with the view that the mechanisms through which the bacterial toxins produce pathology are not entirely foreign to vertebrate cells, at least some of which may possess and employ an analogous mechanism for activation of adenylate cyclase."}
{"id": "PMID:211503", "title": "Nearest-neighbor interactions of the major RNA tumor virus glycoprotein on murine cell surfaces.", "content": "Formaldehyde-fixed Staphylococcus aureus and monospecific antiserum to gp70, the major envelope glycoprotein of murine leukemia virus, were used to immunoadsorb gp70 from Nonidet P40 extracts prepared from surface-radioiodinated murine cells. The labeled gp70 molecules in these cells were linked to a protein of approximately 15,000 daltons via native disulfide bonding. Prior treatment of cells with the reversible, bifunctional, crosslinking reagent dimethyl-3,3'-dithiobispropionimidate, followed by immunoadsorption and two-dimensional diagonal electrophoresis, revealed apparent homodimers and homotrimers of the 85,000-dalton complex. Identical treatment of purified type C RNA tumor virus from murine cells also revealed homodimeric and homotrimeric species, demonstrating similar self-associating tendencies of this glycoprotein in both intact virus and the plasma membrane of nonproducing murine cells. One cross-linked product consistently detected on the surfaces of murine cells was not present after crosslinking of a representative strain of murine leukemia virus.", "contents": "Nearest-neighbor interactions of the major RNA tumor virus glycoprotein on murine cell surfaces. Formaldehyde-fixed Staphylococcus aureus and monospecific antiserum to gp70, the major envelope glycoprotein of murine leukemia virus, were used to immunoadsorb gp70 from Nonidet P40 extracts prepared from surface-radioiodinated murine cells. The labeled gp70 molecules in these cells were linked to a protein of approximately 15,000 daltons via native disulfide bonding. Prior treatment of cells with the reversible, bifunctional, crosslinking reagent dimethyl-3,3'-dithiobispropionimidate, followed by immunoadsorption and two-dimensional diagonal electrophoresis, revealed apparent homodimers and homotrimers of the 85,000-dalton complex. Identical treatment of purified type C RNA tumor virus from murine cells also revealed homodimeric and homotrimeric species, demonstrating similar self-associating tendencies of this glycoprotein in both intact virus and the plasma membrane of nonproducing murine cells. One cross-linked product consistently detected on the surfaces of murine cells was not present after crosslinking of a representative strain of murine leukemia virus."}
{"id": "PMID:211504", "title": "Detection of an early surface change during oncogenic transformation.", "content": "Fluorescamine, which can label surface components of cells grown as monolayers in culture, has been used to probe alterations in chicken embryo fibroblasts infected with a temperature-sensitive  mutant of Rous sarcoma virus, Prague A, LA24. The fluorescence of bound fluorescamine on cells at the permissive temperature (35 degrees) was found to be about 1/3 that of cells cultured at the nonpermissive temperature (41 degrees). During development of the transformed phenotype, i.e., after transfer of the cells from 41 degrees to 35 degrees, the decrease in surface fluorescence was observed to be an early event occurring within the first  4-8 hr after temperature shift. This alteration took place on a time scale similar to that of changes in 2-deoxyglucose transport and an increased rate of DNA synthesis, but before any major morphological changes. The change was related to cell transformation rather than to growth differences of the cells at the two temperatures. Further, it was found that fluorescamine was not monitoring the loss of LETS glycoprotein from the surface or the loss of any other surface components that could be detected by lactoperoxidase-catalyzed iodination of surface proteins. When fluorescamine-labeled components were resolved by polyacrylamide gel electrophoresis, significant differences were seen between components from cells cultured at 35 degrees compared with those from cells cultured at 41 degrees. Based on these results, possible mechanisms accounting for the fluorescence differences are suggested.", "contents": "Detection of an early surface change during oncogenic transformation. Fluorescamine, which can label surface components of cells grown as monolayers in culture, has been used to probe alterations in chicken embryo fibroblasts infected with a temperature-sensitive  mutant of Rous sarcoma virus, Prague A, LA24. The fluorescence of bound fluorescamine on cells at the permissive temperature (35 degrees) was found to be about 1/3 that of cells cultured at the nonpermissive temperature (41 degrees). During development of the transformed phenotype, i.e., after transfer of the cells from 41 degrees to 35 degrees, the decrease in surface fluorescence was observed to be an early event occurring within the first  4-8 hr after temperature shift. This alteration took place on a time scale similar to that of changes in 2-deoxyglucose transport and an increased rate of DNA synthesis, but before any major morphological changes. The change was related to cell transformation rather than to growth differences of the cells at the two temperatures. Further, it was found that fluorescamine was not monitoring the loss of LETS glycoprotein from the surface or the loss of any other surface components that could be detected by lactoperoxidase-catalyzed iodination of surface proteins. When fluorescamine-labeled components were resolved by polyacrylamide gel electrophoresis, significant differences were seen between components from cells cultured at 35 degrees compared with those from cells cultured at 41 degrees. Based on these results, possible mechanisms accounting for the fluorescence differences are suggested."}
{"id": "PMID:211506", "title": "Post-transcriptional suppression of globin gene expression in cells transformed by avian erythroblastosis virus.", "content": "Cells transformed by avian erythroblastosis virus were grown in vitro for up to 5 months. After a few days in culture, synthesis of hemoglobin was undetectable and could not be induced by dimethyl sulfoxide. As shown by globin cDNA hybridization to nuclear and cytoplasmic RNA carried to Crot values of 10(5) moles of nucleotide per liter X sec, globin genes in these cells are transcribed into pre-mRNA, but no trace of globin mRNA appears in the cytoplasm. The implications of this observation for schemes of post-transcriptional regulations and viral transformation are discussed.", "contents": "Post-transcriptional suppression of globin gene expression in cells transformed by avian erythroblastosis virus. Cells transformed by avian erythroblastosis virus were grown in vitro for up to 5 months. After a few days in culture, synthesis of hemoglobin was undetectable and could not be induced by dimethyl sulfoxide. As shown by globin cDNA hybridization to nuclear and cytoplasmic RNA carried to Crot values of 10(5) moles of nucleotide per liter X sec, globin genes in these cells are transcribed into pre-mRNA, but no trace of globin mRNA appears in the cytoplasm. The implications of this observation for schemes of post-transcriptional regulations and viral transformation are discussed."}
{"id": "PMID:211505", "title": "Control of microtubule assembly-disassembly by calcium-dependent regulator protein.", "content": "The Ca2+-dependent regulator (CDR) protein of cyclic nucleotide phosphodiesterase is a low molecular weight, acidic, Ca2+-binding protein which has been implicated in a number of Ca2+-dependent enzymatic functions. Indirect immunofluorescence has revealed that CDR is specifically associated with the chromosome-to-pole region of the mitotic apparatus during metaphase-anaphase in a pattern distinctly different from that of similar cultured cells stained with antitubulin. This characteristic localization in the mitotic half-spindle suggested a role for CDR in the control of microtubule assembly-disassembly during mitosis. Thus, CDR was examined for its effects on microtubule polymerization in vitro. It was determined that stoichiometric concentrations of CDR and a homologous Ca2+-binding protein, skeletal muscle troponin C, both inhibited and reversed microtubule assembly in a Ca2+-dependent manner. CDR-dependent inhibition of in vitro microtubule assembly occurred at physiological Ca2+ concentrations (approximately 10 micron) that, in the absence of CDR, caused only a slight reduction in polymerization. At Ca2+ concentrations in the low physiological range (less than 1 micron), no inhibition was observed. These biochemical results, together with the immunofluorescent localization of CDR in the mitotic half-spindle, provide evidence that Ca2+ is an endogenous regulator of microtubule disassembly through the activity of CDR.", "contents": "Control of microtubule assembly-disassembly by calcium-dependent regulator protein. The Ca2+-dependent regulator (CDR) protein of cyclic nucleotide phosphodiesterase is a low molecular weight, acidic, Ca2+-binding protein which has been implicated in a number of Ca2+-dependent enzymatic functions. Indirect immunofluorescence has revealed that CDR is specifically associated with the chromosome-to-pole region of the mitotic apparatus during metaphase-anaphase in a pattern distinctly different from that of similar cultured cells stained with antitubulin. This characteristic localization in the mitotic half-spindle suggested a role for CDR in the control of microtubule assembly-disassembly during mitosis. Thus, CDR was examined for its effects on microtubule polymerization in vitro. It was determined that stoichiometric concentrations of CDR and a homologous Ca2+-binding protein, skeletal muscle troponin C, both inhibited and reversed microtubule assembly in a Ca2+-dependent manner. CDR-dependent inhibition of in vitro microtubule assembly occurred at physiological Ca2+ concentrations (approximately 10 micron) that, in the absence of CDR, caused only a slight reduction in polymerization. At Ca2+ concentrations in the low physiological range (less than 1 micron), no inhibition was observed. These biochemical results, together with the immunofluorescent localization of CDR in the mitotic half-spindle, provide evidence that Ca2+ is an endogenous regulator of microtubule disassembly through the activity of CDR."}
{"id": "PMID:211507", "title": "Sodium-stimulated active transport of aminoisobutyric acid by reconstituted vesicles from partially purified plasma membranes of mouse fibroblasts transformed by simian virus 40.", "content": "Plasma membrane fractions isolated from mouse fibroblast BALB/c 3T3 cells transformed by simian virus 40 were partially purified by treatment with dimethylmaleic anhydride followed by extraction with 2% cholate. The extracted proteins were combined with exogenous phospholipids and eluted through a Sephadex G50 column. Reconstituted vesicles thus obtained were shown to possess the ability of Na+-stimulated transport of alpha-aminoisobutyric acid. The simultaneous addition of NaSCN and alpha-aminoisobutyric acid to these vesicles produced a transient accumulation above the equilibrium level (overshoot, active transport). The Na+-stimulated transport of alpha-aminoisobutyric acid was sensitive to the accompanying anion and to the temperature of incubation. The results demonstrate that partially purified membrane proteins of mouse fibroblast cells can be incorporated into the liposomes that have the characteristics of Na+-stimulated and electrochemically sensitive active transport of alpha-aminoisobutyric acid.", "contents": "Sodium-stimulated active transport of aminoisobutyric acid by reconstituted vesicles from partially purified plasma membranes of mouse fibroblasts transformed by simian virus 40. Plasma membrane fractions isolated from mouse fibroblast BALB/c 3T3 cells transformed by simian virus 40 were partially purified by treatment with dimethylmaleic anhydride followed by extraction with 2% cholate. The extracted proteins were combined with exogenous phospholipids and eluted through a Sephadex G50 column. Reconstituted vesicles thus obtained were shown to possess the ability of Na+-stimulated transport of alpha-aminoisobutyric acid. The simultaneous addition of NaSCN and alpha-aminoisobutyric acid to these vesicles produced a transient accumulation above the equilibrium level (overshoot, active transport). The Na+-stimulated transport of alpha-aminoisobutyric acid was sensitive to the accompanying anion and to the temperature of incubation. The results demonstrate that partially purified membrane proteins of mouse fibroblast cells can be incorporated into the liposomes that have the characteristics of Na+-stimulated and electrochemically sensitive active transport of alpha-aminoisobutyric acid."}
{"id": "PMID:211508", "title": "Molecular genetics of herpes simplex virus: demonstration of regions of obligatory and nonobligatory identity within diploid regions of the genome by sequence replacement and insertion.", "content": "The DNAs of herpes simplex virus (HSV) 1 and 2 consist of two components, L and S, each composed of unique sequences bracketed by inverted repeats. In this study we have probed the structure of the reiterated regions of the S component in marker rescue experiments involving transfection of cells with mixtures of intact HSV-1 mutant viral DNA and individual DNA fragments generated by restriction endonuclease digestion of wild-type HSV-1 or HSV-2 DNAs. The results were as follows: (i) HSV is diploid for the wild-type sequences that rescue two temperature-sensitive (ts) mutants. DNA fragments from both reiterated regions of the S component of HSV-1(F) DNA can rescue tsLB2 and tsD mutants. (ii) Identity of the entire reiterated sequence at both ends of S is not obligatory because only one end of the S component of wild phenotype virus HSV-1(1061) rescues tsD even though both ends rescue tsLB2. (iii) Genes in both reiterated sequences can be expressed. We produced, by marker rescue experiments, recombinants with heterotypic ends of the S component, and these specified corresponding polypeptides characteristic of both HSV-1 and HSV-2. (iv) The reiterated sequences of the S component may contain a region of obligatory identity. Thus, several recombinant clones produced by rescue with HSV-2 DNA contained identical HSV-2 DNA insertions within both reiterated regions of the HSV-1 S component. Consistent with this conclusion, the termini of the S component in the heterodiploids described in iii were identical by restriction enzyme analysis. (v) The observation that HSV DNA can be expanded by at least 5 x 10(6) by means of insertion in the S component suggests that it can be a vehicle for exogenous DNA.", "contents": "Molecular genetics of herpes simplex virus: demonstration of regions of obligatory and nonobligatory identity within diploid regions of the genome by sequence replacement and insertion. The DNAs of herpes simplex virus (HSV) 1 and 2 consist of two components, L and S, each composed of unique sequences bracketed by inverted repeats. In this study we have probed the structure of the reiterated regions of the S component in marker rescue experiments involving transfection of cells with mixtures of intact HSV-1 mutant viral DNA and individual DNA fragments generated by restriction endonuclease digestion of wild-type HSV-1 or HSV-2 DNAs. The results were as follows: (i) HSV is diploid for the wild-type sequences that rescue two temperature-sensitive (ts) mutants. DNA fragments from both reiterated regions of the S component of HSV-1(F) DNA can rescue tsLB2 and tsD mutants. (ii) Identity of the entire reiterated sequence at both ends of S is not obligatory because only one end of the S component of wild phenotype virus HSV-1(1061) rescues tsD even though both ends rescue tsLB2. (iii) Genes in both reiterated sequences can be expressed. We produced, by marker rescue experiments, recombinants with heterotypic ends of the S component, and these specified corresponding polypeptides characteristic of both HSV-1 and HSV-2. (iv) The reiterated sequences of the S component may contain a region of obligatory identity. Thus, several recombinant clones produced by rescue with HSV-2 DNA contained identical HSV-2 DNA insertions within both reiterated regions of the HSV-1 S component. Consistent with this conclusion, the termini of the S component in the heterodiploids described in iii were identical by restriction enzyme analysis. (v) The observation that HSV DNA can be expanded by at least 5 x 10(6) by means of insertion in the S component suggests that it can be a vehicle for exogenous DNA."}
{"id": "PMID:211509", "title": "Abelson antigen: a viral tumor antigen that is also a differentiation antigen of BALB/c mice.", "content": "We report here the serologic detection of a cell surface antigen common to cells transformed by the Abelson murine leukemia virus (A-MuLV) and to normal hematopoietic cells from certain strains of mice. Serum from C57BL/6 mice hyperimmunized with syngeneic A-MuLV lymphoma cells was cytotoxic for the immunizing cells; this reaction was used as the serologic test system for recognition of A-MuLV antigens. Absorption analysis using 40 tumors and 21 cell lines revealed that two serologic specificities were detected by this test system: (i) FMR antigen(s) related to the Moloney MuLV helper (the virus from which A-MuLV was originally derived), and (ii) an antigen expressed on all cells transformed by A-MuLV. The A-MuLV-specific antigen was also present on uninfected cells from BALB/c bone marrow, spleen, and fetal liver but not from adult liver, thymus, lymph nodes, or peripheral blood. Abelson antigen was not expressed on bone marrow or spleen cells of 12 other mouse strains. In light of the original isolation of A-MuLV from a BALB/c mouse infected with Moloney virus, it is possible that Abelson antigen is a serologic marker for a gene of BALB/c mice, normally encoding a cell surface molecule, that was incorporated into the Moloney virus genome during the generation of A-MuLV.", "contents": "Abelson antigen: a viral tumor antigen that is also a differentiation antigen of BALB/c mice. We report here the serologic detection of a cell surface antigen common to cells transformed by the Abelson murine leukemia virus (A-MuLV) and to normal hematopoietic cells from certain strains of mice. Serum from C57BL/6 mice hyperimmunized with syngeneic A-MuLV lymphoma cells was cytotoxic for the immunizing cells; this reaction was used as the serologic test system for recognition of A-MuLV antigens. Absorption analysis using 40 tumors and 21 cell lines revealed that two serologic specificities were detected by this test system: (i) FMR antigen(s) related to the Moloney MuLV helper (the virus from which A-MuLV was originally derived), and (ii) an antigen expressed on all cells transformed by A-MuLV. The A-MuLV-specific antigen was also present on uninfected cells from BALB/c bone marrow, spleen, and fetal liver but not from adult liver, thymus, lymph nodes, or peripheral blood. Abelson antigen was not expressed on bone marrow or spleen cells of 12 other mouse strains. In light of the original isolation of A-MuLV from a BALB/c mouse infected with Moloney virus, it is possible that Abelson antigen is a serologic marker for a gene of BALB/c mice, normally encoding a cell surface molecule, that was incorporated into the Moloney virus genome during the generation of A-MuLV."}
{"id": "PMID:211510", "title": "Cells nonproductively transformed by Abelson murine leukemia virus express a high molecular weight polyprotein containing structural and nonstructural components.", "content": "Cell clones nonproductively transformed by the replication-defective Abelson strain of murine leukemia virus (AbLV) were analyzed for type C viral antigen expression by competition immunoassay. AbLV-transformed mink non-producer lines were found to express a 110,000- to 130,000-molecular weight polyprotein containing murine leukemia virus gag proteins p15 and p12 covalently linked to nonstructural AbLV-coded component(s) of around 80,000-100,000 molecular weight. This polyprotein lacked detectable antigenic cross-reactivity with other virion-coded gag gene proteins such as p30, p10, the viral reverse transcriptase (RNA-dependent DNA polymerase), or the major viral envelope glycoprotein, gp70. By analogy to earlier data on feline and avian sarcoma viruses, these results suggest that a portion of this polyprotein might represent the AbLV src gene product and that in translation it is initially linked in precursor form to gag structural proteins. Superinfection of mink cells nonproductively transformed by AbLV--with either a wild mouse amphotropic type C virus isolate, 4070-A, or with the endogenous cat virus, RD114--led to production of pseudotype virus containing high concentrations of the AbLV-coded precursor polyprotein.", "contents": "Cells nonproductively transformed by Abelson murine leukemia virus express a high molecular weight polyprotein containing structural and nonstructural components. Cell clones nonproductively transformed by the replication-defective Abelson strain of murine leukemia virus (AbLV) were analyzed for type C viral antigen expression by competition immunoassay. AbLV-transformed mink non-producer lines were found to express a 110,000- to 130,000-molecular weight polyprotein containing murine leukemia virus gag proteins p15 and p12 covalently linked to nonstructural AbLV-coded component(s) of around 80,000-100,000 molecular weight. This polyprotein lacked detectable antigenic cross-reactivity with other virion-coded gag gene proteins such as p30, p10, the viral reverse transcriptase (RNA-dependent DNA polymerase), or the major viral envelope glycoprotein, gp70. By analogy to earlier data on feline and avian sarcoma viruses, these results suggest that a portion of this polyprotein might represent the AbLV src gene product and that in translation it is initially linked in precursor form to gag structural proteins. Superinfection of mink cells nonproductively transformed by AbLV--with either a wild mouse amphotropic type C virus isolate, 4070-A, or with the endogenous cat virus, RD114--led to production of pseudotype virus containing high concentrations of the AbLV-coded precursor polyprotein."}
{"id": "PMID:211511", "title": "Calcitonin and calcium ionophores: cyclic AMP responses in cells of a human lymphoid line.", "content": "Receptors for calcitonin, as assayed by the specific binding of 125I-labeled salmon calcitonin and stimulation of cyclic AMP formation, were found in 8866 cells derived from a human lymphoid line. The affinity of calcitonin from different species and of various analogues of human calcitonin for the binding sites and their ability to stimulate cyclic AMP formation were closely related to their hypocalcemic activity and presumably reflected biological properties of the hormones. Besides calcitonin, prostaglandin E1 and beta-adrenergic catecholamines stimulated cyclic AMP formation in these cells. The calcium ionophores, A23187 and Br-X-573A, did not influence the specific binding of 125I-labeled salmon calcitonin. A23187, however, suppressed basal and calcitonin-stimulated formation of cyclic AMP in the presence of at least 0.6 mM calcium in the incubation medium. Br-X-537A did not require extracellular calcium to suppress basal and calcitonin-stimulated formation of cyclic AMP, suggesting that the release of calcium from internal stores may regulate adenylyate cyclase activity in 8866 cells.", "contents": "Calcitonin and calcium ionophores: cyclic AMP responses in cells of a human lymphoid line. Receptors for calcitonin, as assayed by the specific binding of 125I-labeled salmon calcitonin and stimulation of cyclic AMP formation, were found in 8866 cells derived from a human lymphoid line. The affinity of calcitonin from different species and of various analogues of human calcitonin for the binding sites and their ability to stimulate cyclic AMP formation were closely related to their hypocalcemic activity and presumably reflected biological properties of the hormones. Besides calcitonin, prostaglandin E1 and beta-adrenergic catecholamines stimulated cyclic AMP formation in these cells. The calcium ionophores, A23187 and Br-X-573A, did not influence the specific binding of 125I-labeled salmon calcitonin. A23187, however, suppressed basal and calcitonin-stimulated formation of cyclic AMP in the presence of at least 0.6 mM calcium in the incubation medium. Br-X-537A did not require extracellular calcium to suppress basal and calcitonin-stimulated formation of cyclic AMP, suggesting that the release of calcium from internal stores may regulate adenylyate cyclase activity in 8866 cells."}
{"id": "PMID:211512", "title": "Growth factors from murine sarcoma virus-transformed cells.", "content": "Murine sarcoma virus-transformed mouse fibroblasts produce polypeptide growth factors and release them into serum-free medium. These factors stimulate cells to divide in monolayer cultures and also to form colonies that grow progressively soft agar. Three major peaks of activity are seen, with apparent molecular weights of 25,000, 12,000, and 7000. The sarcoma growth factors are heat-stable, trypsin-sensitive, and active in nanogram quantities when tested for growth stimulation of untransformed rat and mouse fibroblasts. All three molecular species are also capable of competing for membrane epidermal growth factor (EGF) receptors when tested with 125I-labeled EGF. They differ from mouse EGF, however, in their molecular weights, in their inability to react with anti-EGF antibodies, and in their ability to convert cells to anchorage independent (agar) growth. For the above reasons, we conclude that the sarcoma growth factors are a new class of polypeptide tropic factors that confer on fibroblasts in vitro properties associated with the transformed phenotype.", "contents": "Growth factors from murine sarcoma virus-transformed cells. Murine sarcoma virus-transformed mouse fibroblasts produce polypeptide growth factors and release them into serum-free medium. These factors stimulate cells to divide in monolayer cultures and also to form colonies that grow progressively soft agar. Three major peaks of activity are seen, with apparent molecular weights of 25,000, 12,000, and 7000. The sarcoma growth factors are heat-stable, trypsin-sensitive, and active in nanogram quantities when tested for growth stimulation of untransformed rat and mouse fibroblasts. All three molecular species are also capable of competing for membrane epidermal growth factor (EGF) receptors when tested with 125I-labeled EGF. They differ from mouse EGF, however, in their molecular weights, in their inability to react with anti-EGF antibodies, and in their ability to convert cells to anchorage independent (agar) growth. For the above reasons, we conclude that the sarcoma growth factors are a new class of polypeptide tropic factors that confer on fibroblasts in vitro properties associated with the transformed phenotype."}
{"id": "PMID:211513", "title": "Ontogeny of synaptic phosphoproteins in brain.", "content": "The ontogeny of two endogenous substrates for cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase; EC 2.7.1.37) has been studied in rat and guinea pig cerebrum. These endogenous substrates, referred to as proteins Ia and Ib, have been shown in other studies to be specific to nervous tissue and to be enriched in the synaptic membrane and synaptic vesicle fractions of adult brain. In the present study, proteins Ia and Ib were shown to increase markedly during the time of major synaptogenesis in rat cerebrum and guinea pig cerebrum, in which the morphological development of synapses is predominantly postnatal and prenatal, respectively. Similar results were obtained either by measuring endogenous phosphorylation of proteins Ia and Ib in the synaptic membrane fraction or by measuring phosphorylation of extracted proteins Ia and Ib with added protein kinase.", "contents": "Ontogeny of synaptic phosphoproteins in brain. The ontogeny of two endogenous substrates for cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase; EC 2.7.1.37) has been studied in rat and guinea pig cerebrum. These endogenous substrates, referred to as proteins Ia and Ib, have been shown in other studies to be specific to nervous tissue and to be enriched in the synaptic membrane and synaptic vesicle fractions of adult brain. In the present study, proteins Ia and Ib were shown to increase markedly during the time of major synaptogenesis in rat cerebrum and guinea pig cerebrum, in which the morphological development of synapses is predominantly postnatal and prenatal, respectively. Similar results were obtained either by measuring endogenous phosphorylation of proteins Ia and Ib in the synaptic membrane fraction or by measuring phosphorylation of extracted proteins Ia and Ib with added protein kinase."}
{"id": "PMID:211514", "title": "A Drosophila mutant with a temperature-sensitive block in nerve conduction.", "content": "A mutant, napts (no action potential, temperature-sensitive), is described in which axonal conduction fails at high temperature. Synaptic transmission at the larval neuromuscular junction is unimpaired. Larvae and adults are rapidly paralyzed at restrictive temperatures; they recover rapidly when the temperature is decreased. The mutant gene is recessive and is located on the second chromosome at map position 56.", "contents": "A Drosophila mutant with a temperature-sensitive block in nerve conduction. A mutant, napts (no action potential, temperature-sensitive), is described in which axonal conduction fails at high temperature. Synaptic transmission at the larval neuromuscular junction is unimpaired. Larvae and adults are rapidly paralyzed at restrictive temperatures; they recover rapidly when the temperature is decreased. The mutant gene is recessive and is located on the second chromosome at map position 56."}
{"id": "PMID:211515", "title": "Regulation of aldosterone secretion by the renin-angiotensin system during sodium restriction in rats.", "content": "The role of angiotensin II as mediator of the aldosterone response to short periods of sodium restriction was studied in rats by administration of a converting enzyme inhibitor to block formation of the octapeptide throughout the duration of decreased sodium intake. In control animals, short-term sodium restriction caused increased levels of adrenal receptors for angiotensin II, with enhancement of early and late steps in aldosterone biosynthesis and elevation of plasma aldosterone concentration. Each of these changes induced by sodium deficiency was abolished during blockade of angiotensin II formation by continuous infusion of the converting enzyme inhibitor, SQ 14,225. The absolute dependence of adrenal glomerulosa cell responses on angiotensin II formation indicates that the renin-angiotensin system is the primary regulator of aldosterone secretion during physiological fluctuations in sodium intake.", "contents": "Regulation of aldosterone secretion by the renin-angiotensin system during sodium restriction in rats. The role of angiotensin II as mediator of the aldosterone response to short periods of sodium restriction was studied in rats by administration of a converting enzyme inhibitor to block formation of the octapeptide throughout the duration of decreased sodium intake. In control animals, short-term sodium restriction caused increased levels of adrenal receptors for angiotensin II, with enhancement of early and late steps in aldosterone biosynthesis and elevation of plasma aldosterone concentration. Each of these changes induced by sodium deficiency was abolished during blockade of angiotensin II formation by continuous infusion of the converting enzyme inhibitor, SQ 14,225. The absolute dependence of adrenal glomerulosa cell responses on angiotensin II formation indicates that the renin-angiotensin system is the primary regulator of aldosterone secretion during physiological fluctuations in sodium intake."}
{"id": "PMID:211533", "title": "Effects of the acute administration of ethanol on the sleep of the rat: a dose-response study.", "content": "Seven-hr sleep recordings were performed on rats following intraperitoneal injection of saline or one of four doses of ethanol (1.1, 1.5, 2.0 or 2.5 g/kg). Total minutes of REM sleep and percentage REM sleep were decreased in a dose-dependent manner. Percentage nonREM sleep increased with progressively higher doses. The decrease in REM sleep appeared to be related to a decrease in the number of REM sleep episodes and an increase in the length of the REM-nonREM cycle. Other variables such as mean length of REM sleep episodes and REM sleep efficiency were unchanged. An analysis of the first and second 3.5 hr of the recording showed that ethanol continued to have marked effects on REM and nonREM sleep during the second 3.5 hr, when blood levels were declining. Ethanol produced decreases in sleep latency, but total sleep time was unchanged.", "contents": "Effects of the acute administration of ethanol on the sleep of the rat: a dose-response study. Seven-hr sleep recordings were performed on rats following intraperitoneal injection of saline or one of four doses of ethanol (1.1, 1.5, 2.0 or 2.5 g/kg). Total minutes of REM sleep and percentage REM sleep were decreased in a dose-dependent manner. Percentage nonREM sleep increased with progressively higher doses. The decrease in REM sleep appeared to be related to a decrease in the number of REM sleep episodes and an increase in the length of the REM-nonREM cycle. Other variables such as mean length of REM sleep episodes and REM sleep efficiency were unchanged. An analysis of the first and second 3.5 hr of the recording showed that ethanol continued to have marked effects on REM and nonREM sleep during the second 3.5 hr, when blood levels were declining. Ethanol produced decreases in sleep latency, but total sleep time was unchanged."}
{"id": "PMID:211534", "title": "Foreign-body reaction to silicone gel in axillary lymph nodes after an augmentation mammaplasty.", "content": "A radical mastectomy was performed for a breast adenocarcinoma occurring 10 years after a subpectoral augmentation mammaplasty with silicone gel-filled prostheses. A foreign-body reaction to silicone was seen in two of the axillary lymph nodes resected.", "contents": "Foreign-body reaction to silicone gel in axillary lymph nodes after an augmentation mammaplasty. A radical mastectomy was performed for a breast adenocarcinoma occurring 10 years after a subpectoral augmentation mammaplasty with silicone gel-filled prostheses. A foreign-body reaction to silicone was seen in two of the axillary lymph nodes resected."}
{"id": "PMID:211535", "title": "Proteoglycans and collagenase in hypertrophic scar formation.", "content": "The collagen fibers of the nodules and whorl-like figures in hypertrophic scars are \"coated\" with proteoglycans, mainly chondroitin-4-sulfate. The latter was shown to prevent collagenase from breaking down collagen. This suggests that the presence of great amounts of chondroitin-4-sulfate in hypertrophic scars may contribute to the overabundance of collagen deposition which is characteristic of this abnormal healing process.", "contents": "Proteoglycans and collagenase in hypertrophic scar formation. The collagen fibers of the nodules and whorl-like figures in hypertrophic scars are \"coated\" with proteoglycans, mainly chondroitin-4-sulfate. The latter was shown to prevent collagenase from breaking down collagen. This suggests that the presence of great amounts of chondroitin-4-sulfate in hypertrophic scars may contribute to the overabundance of collagen deposition which is characteristic of this abnormal healing process."}
{"id": "PMID:211539", "title": "Ultrastructural changes in the placenta of the ewe after fetal pituitary stalk section.", "content": "Binucleate cells are a normal component of the ovine chorionic epithelium, but are usually separated from the fetal-maternal interface by a thin layer of cytoplasm derived from the principal or uni-nucleate cells of the trophoblast. They are distinguished not only by two distinct and separate nuclei, but also by conspicuous membrane-bound cytoplasmic inclusions in the form of haloed droplets. After fetal pituitary stalk section binucleate cells move up to and participate in the formation of the fetal-maternal interface; furthermore they extend clear blunt-ended pseudopodia into the maternal epithelial syncytium. These activities do not appear to be supppressed by fetal infusion of cortisol or ACTH. The apparent motility of binucleate cells, together with the presence of haloed droplets within the maternal epithelial syncytium, suggests that after fetal pituitary stalk section binucleate cells invade the uterine syncytium, lose their limiting membranes and discharge their contents into the syncytial cytoplasm. Large molecules such as ovine placental lactogen may be transported from fetal to maternal tissues by this mechanism.", "contents": "Ultrastructural changes in the placenta of the ewe after fetal pituitary stalk section. Binucleate cells are a normal component of the ovine chorionic epithelium, but are usually separated from the fetal-maternal interface by a thin layer of cytoplasm derived from the principal or uni-nucleate cells of the trophoblast. They are distinguished not only by two distinct and separate nuclei, but also by conspicuous membrane-bound cytoplasmic inclusions in the form of haloed droplets. After fetal pituitary stalk section binucleate cells move up to and participate in the formation of the fetal-maternal interface; furthermore they extend clear blunt-ended pseudopodia into the maternal epithelial syncytium. These activities do not appear to be supppressed by fetal infusion of cortisol or ACTH. The apparent motility of binucleate cells, together with the presence of haloed droplets within the maternal epithelial syncytium, suggests that after fetal pituitary stalk section binucleate cells invade the uterine syncytium, lose their limiting membranes and discharge their contents into the syncytial cytoplasm. Large molecules such as ovine placental lactogen may be transported from fetal to maternal tissues by this mechanism."}
{"id": "PMID:211540", "title": "Computed transaxial imaging using single gamma emitters.", "content": "Emission computed tomography (ECT) studies were performed on test objects and dogs. Conjugate views were obtained for 60 to 120 projections equispaced around 360 degrees by rotation of the subjects in front of a gamma camera. A convolution reconstruction algorithm in which gamma ray attenuation corrections are included in the backprojection step were used to reconstruct the emission images. Reconstructions of x-ray transmission data provided data for gamma ray attenuation corrections of the emission images of 99mTc-pyrophosphate uptake in dogs. Reconstructed images of test objects show spatial resolution uniformity, and attenuation corrections enable estimation of relative activity densities to within 10--15% rms errors, thus demonstrating quantitative imaging capabilities of emission CT.", "contents": "Computed transaxial imaging using single gamma emitters. Emission computed tomography (ECT) studies were performed on test objects and dogs. Conjugate views were obtained for 60 to 120 projections equispaced around 360 degrees by rotation of the subjects in front of a gamma camera. A convolution reconstruction algorithm in which gamma ray attenuation corrections are included in the backprojection step were used to reconstruct the emission images. Reconstructions of x-ray transmission data provided data for gamma ray attenuation corrections of the emission images of 99mTc-pyrophosphate uptake in dogs. Reconstructed images of test objects show spatial resolution uniformity, and attenuation corrections enable estimation of relative activity densities to within 10--15% rms errors, thus demonstrating quantitative imaging capabilities of emission CT."}
{"id": "PMID:211541", "title": "[Postnatal development of the epithelium of the small intestine of guinea-pigs (author's transl)].", "content": "This investigation deals with the histochemical, biochemical and electron microscopical development of the postnatal epithelium in the small intestine of guinea-pigs. Immediately after birth the enterocytes of the whole small intestine are rich in glycogen. Within 48 hours the glycogen in broken down by intralysosomal digestion and glycogenolysis or disappears from the villus epithelium by extrusion of the absorptive cells. The first loss of glycogen occurs in the jejunum; at the latest it leaves the lining epithelium of the ileum so that a proxoim-distal gradient exists. Afterwards for maximal 14 days fat ist taken up from the mother's milk only by the enterocytes of the jejunum without any signs of endocytosis; the bigger part of the fat leaves the cells by exocytosis and enters the intercellular space. Most of the lipid reaches the lymphatics or is absorbed by marcophages; only small amounts are found in the blood capillaries. The number of the enterocytes engaged in the absorption and passage of fat depends on its quantity in the lumen of the small intestine. During the first days of life everywhere in the small intestine the ultrastructure of the enterocytes is characterized by 2 types of mitochondria (large and small ones with different internal structure). Furthermore in the ileum the absorptive cells contain more lysosomes and a more extensive inframicrovillous membrane system than in jejunum. The membrane system consists of aggregated tubules, vacuoles and vesicles; they are situated below the microvilli and sometimes communicate with the lumen of the gut. The big mitochondria are broken down in the lysosomes or appear in the lumen of the small bowel following extrusion of the enterocytes. The lysosomes are involved in autophagic (digestion of glycogen and cell organelles) as well as in autophagic processes (hydrolysis of molecules from the mother's milk and foreign food). These substances are probably incorporated by means of the inframicrovillous membrane system. With respect to the microvillous hydrolases (lactase, alpha-D-glucosidases, peptidases, alkaline phosphatase) histochemical and biochemical assays were carried out with the same artificial substrate. The results depend on the method employed and the enzyme investigated. Using histochemical techniques and indolyl, naphthly, naphthol AS or naphthylamine derivatives as substrates the activity of peptidases and alkaline phosphatase correspond to that in adult guinea-pigs already at the time of birth; alpha-D-glucosidases (glucoamylase, saccharaseisomaltase) become mature at the end of the first, and the development of lactase is finished after the second week of life. For the biochemical investigations (fluorometric measurements of naphthol and naphthylamine) of microvillous enzymes with naphthyl and naphthylamine substrates a new technique of homogenisation using freeze-dried cryostate sections is successfully employed...", "contents": "[Postnatal development of the epithelium of the small intestine of guinea-pigs (author's transl)]. This investigation deals with the histochemical, biochemical and electron microscopical development of the postnatal epithelium in the small intestine of guinea-pigs. Immediately after birth the enterocytes of the whole small intestine are rich in glycogen. Within 48 hours the glycogen in broken down by intralysosomal digestion and glycogenolysis or disappears from the villus epithelium by extrusion of the absorptive cells. The first loss of glycogen occurs in the jejunum; at the latest it leaves the lining epithelium of the ileum so that a proxoim-distal gradient exists. Afterwards for maximal 14 days fat ist taken up from the mother's milk only by the enterocytes of the jejunum without any signs of endocytosis; the bigger part of the fat leaves the cells by exocytosis and enters the intercellular space. Most of the lipid reaches the lymphatics or is absorbed by marcophages; only small amounts are found in the blood capillaries. The number of the enterocytes engaged in the absorption and passage of fat depends on its quantity in the lumen of the small intestine. During the first days of life everywhere in the small intestine the ultrastructure of the enterocytes is characterized by 2 types of mitochondria (large and small ones with different internal structure). Furthermore in the ileum the absorptive cells contain more lysosomes and a more extensive inframicrovillous membrane system than in jejunum. The membrane system consists of aggregated tubules, vacuoles and vesicles; they are situated below the microvilli and sometimes communicate with the lumen of the gut. The big mitochondria are broken down in the lysosomes or appear in the lumen of the small bowel following extrusion of the enterocytes. The lysosomes are involved in autophagic (digestion of glycogen and cell organelles) as well as in autophagic processes (hydrolysis of molecules from the mother's milk and foreign food). These substances are probably incorporated by means of the inframicrovillous membrane system. With respect to the microvillous hydrolases (lactase, alpha-D-glucosidases, peptidases, alkaline phosphatase) histochemical and biochemical assays were carried out with the same artificial substrate. The results depend on the method employed and the enzyme investigated. Using histochemical techniques and indolyl, naphthly, naphthol AS or naphthylamine derivatives as substrates the activity of peptidases and alkaline phosphatase correspond to that in adult guinea-pigs already at the time of birth; alpha-D-glucosidases (glucoamylase, saccharaseisomaltase) become mature at the end of the first, and the development of lactase is finished after the second week of life. For the biochemical investigations (fluorometric measurements of naphthol and naphthylamine) of microvillous enzymes with naphthyl and naphthylamine substrates a new technique of homogenisation using freeze-dried cryostate sections is successfully employed..."}
{"id": "PMID:211567", "title": "Effect of lead ingestion on vitamin D3 metabolism in Japanese quail.", "content": "Immature female Japanese quail were given either lead acetate or sodium acetate in the drinking water for 15 days. In vitro kidney production of 1, 25- and 24-25- dihydroxyvitamin D3 from tritiated 25-hydroxyvitamin D3 was measured. At all 3 dose levels of lead acetate (0.32, 3.2 and 32 mg Pb/ml), in vitro kidney production of 1,25-(OH)2D3 was increased significantly compared to control levels treated with sodium acetate. Lead treatment had no significant effect on plasma calcium and inorganic phosphate levels.", "contents": "Effect of lead ingestion on vitamin D3 metabolism in Japanese quail. Immature female Japanese quail were given either lead acetate or sodium acetate in the drinking water for 15 days. In vitro kidney production of 1, 25- and 24-25- dihydroxyvitamin D3 from tritiated 25-hydroxyvitamin D3 was measured. At all 3 dose levels of lead acetate (0.32, 3.2 and 32 mg Pb/ml), in vitro kidney production of 1,25-(OH)2D3 was increased significantly compared to control levels treated with sodium acetate. Lead treatment had no significant effect on plasma calcium and inorganic phosphate levels."}
{"id": "PMID:211569", "title": "[Neurological disorders and perhexiline maleate therapy. Clinical study of 10 cases. Neuropathological, pharmacocinetic and biochemical studies (author's transl)].", "content": "Ten new cases of perhexiline induced peripheral neuropathies are reported. The authors emphasize the possible association of other neurological disorders: cerebellar symptoms in one case, complex tremor in two other cases, marked decrease of photomotor reflexes in one case and disgeusia in another one. The pharmacocinetic study of 4 cases revealed the presence of a low metabolism of the drug in one of them. Polymorphous inclusions have been seen in Schwann cell and endothelial cell cytoplasm in the three patients with electron microscopic study of the nerves. The pathological study of one case showed the demyelination of spinal cord posterior columns. In another case, who died from hepatic coma, the biochemical study of cerebral lipids revealed the low values of cerebrosides and sulfatides in cerebellum and cerebral white matter.", "contents": "[Neurological disorders and perhexiline maleate therapy. Clinical study of 10 cases. Neuropathological, pharmacocinetic and biochemical studies (author's transl)]. Ten new cases of perhexiline induced peripheral neuropathies are reported. The authors emphasize the possible association of other neurological disorders: cerebellar symptoms in one case, complex tremor in two other cases, marked decrease of photomotor reflexes in one case and disgeusia in another one. The pharmacocinetic study of 4 cases revealed the presence of a low metabolism of the drug in one of them. Polymorphous inclusions have been seen in Schwann cell and endothelial cell cytoplasm in the three patients with electron microscopic study of the nerves. The pathological study of one case showed the demyelination of spinal cord posterior columns. In another case, who died from hepatic coma, the biochemical study of cerebral lipids revealed the low values of cerebrosides and sulfatides in cerebellum and cerebral white matter."}
{"id": "PMID:211570", "title": "[Change in recurrent inhibition when standing in normal subjects and spastics (author's transl)].", "content": "In normal subjects and patients with diseases of the upper motor neurone, recurrent inhibition directed to soleus motoneurones was studied in three different postures: sitting (control situation), standing when leaning backward on a wall, standing independently without the support of a wall. In normal subjects, this recurrent inhibition was not modified when standing with the support of a wall, while it was enhanced when standing without such a support.", "contents": "[Change in recurrent inhibition when standing in normal subjects and spastics (author's transl)]. In normal subjects and patients with diseases of the upper motor neurone, recurrent inhibition directed to soleus motoneurones was studied in three different postures: sitting (control situation), standing when leaning backward on a wall, standing independently without the support of a wall. In normal subjects, this recurrent inhibition was not modified when standing with the support of a wall, while it was enhanced when standing without such a support."}
{"id": "PMID:211571", "title": "[\"Functional and anatomical organization of associative\" cortical areas 7, 21 and 22 in monkeys. A study of the cortical projections from the pulvinar by means of HRP tracing technique (author's transl)].", "content": "The thalamic projections to the parietal and temporal associative areas (Brodmann's areas 7, 21 and 22) have been revealed by means of the retrograde axonal transport of horseradish peroxidase (HRP). The medial pulvinar (PM) was found to send afferents to the three studied areas. Labelled neurones of the PM appeared to be grouped in terms of their cortical target; indeed, neurones of origin of projection fibres to areas 7, 21 and 22 were respectively localized in the dorso-lateral, ventro-lateral and ventro-medial part of the PM. Although the multimodal sensory nature of the PM has been demonstrated by electrophysiological works, the function of PM neurones and the significance of their topographical repartition remain unknown. However PM could be involved in the transmission of specific sensory informations to the three associative areas 7, 21 and 22. Such an hypothesis is discussed according to the hitherto available data.", "contents": "[\"Functional and anatomical organization of associative\" cortical areas 7, 21 and 22 in monkeys. A study of the cortical projections from the pulvinar by means of HRP tracing technique (author's transl)]. The thalamic projections to the parietal and temporal associative areas (Brodmann's areas 7, 21 and 22) have been revealed by means of the retrograde axonal transport of horseradish peroxidase (HRP). The medial pulvinar (PM) was found to send afferents to the three studied areas. Labelled neurones of the PM appeared to be grouped in terms of their cortical target; indeed, neurones of origin of projection fibres to areas 7, 21 and 22 were respectively localized in the dorso-lateral, ventro-lateral and ventro-medial part of the PM. Although the multimodal sensory nature of the PM has been demonstrated by electrophysiological works, the function of PM neurones and the significance of their topographical repartition remain unknown. However PM could be involved in the transmission of specific sensory informations to the three associative areas 7, 21 and 22. Such an hypothesis is discussed according to the hitherto available data."}
{"id": "PMID:211576", "title": "Plasma cholesterol esterification and plasma lipoproteins in bile-duct-ligated dogs.", "content": "To study the lipoprotein changes in cholestasis while the capacity for plasma cholesterol esterification was normal, the common bile duct was ligated in dogs and plasma investigated 8 h and 48 h later. The plasma concentration of cholesteryl esters was slightly increased, concomitant with a tendency toward an increase in the activity of lecithin:cholesterol acyltransferase (LCAT). The content of cholesteryl esters in the main lipoprotein classes was normal. Marked alteration in the low density lipoproteins (LDL) and the high density lipoproteins (HDL) took place and were essentially similar 8 h and 48 h after bile duct ligation. In LDL, (density 1.006--1.019 g/ml) and LDL2 (density 1.019--1.063 g/ml) an increase in the content of polar lipids was observed, and in LDL2 heterogeneity in particle size was demonstrated by gelfiltration on 2% agarose and by electron microsopcy. Large myelin structures, flattened disc-shaped particles, and particles with the appearance of normal LDL2 were present. HDL isolated after operation was characterized by a decreased protein/lipid ratio and an increased content of phospholipids. By gelfiltration on Sephadex G-200 and by electron microscopy changes in particle size were observed, with the presence of disc-shaped particles with a tendency in form rouleaux. These results demonstrate that marked lipoprotein changes occur as early as 8 h after bile duct-ligation in dogs and indicate that a deficient LCAT mechanism is present in cholestasis even with normal or high plasma LCAT activity.", "contents": "Plasma cholesterol esterification and plasma lipoproteins in bile-duct-ligated dogs. To study the lipoprotein changes in cholestasis while the capacity for plasma cholesterol esterification was normal, the common bile duct was ligated in dogs and plasma investigated 8 h and 48 h later. The plasma concentration of cholesteryl esters was slightly increased, concomitant with a tendency toward an increase in the activity of lecithin:cholesterol acyltransferase (LCAT). The content of cholesteryl esters in the main lipoprotein classes was normal. Marked alteration in the low density lipoproteins (LDL) and the high density lipoproteins (HDL) took place and were essentially similar 8 h and 48 h after bile duct ligation. In LDL, (density 1.006--1.019 g/ml) and LDL2 (density 1.019--1.063 g/ml) an increase in the content of polar lipids was observed, and in LDL2 heterogeneity in particle size was demonstrated by gelfiltration on 2% agarose and by electron microsopcy. Large myelin structures, flattened disc-shaped particles, and particles with the appearance of normal LDL2 were present. HDL isolated after operation was characterized by a decreased protein/lipid ratio and an increased content of phospholipids. By gelfiltration on Sephadex G-200 and by electron microscopy changes in particle size were observed, with the presence of disc-shaped particles with a tendency in form rouleaux. These results demonstrate that marked lipoprotein changes occur as early as 8 h after bile duct-ligation in dogs and indicate that a deficient LCAT mechanism is present in cholestasis even with normal or high plasma LCAT activity."}
{"id": "PMID:211577", "title": "Upper extremity deformities associated with the orofacial clefts.", "content": "A material of 89 cases of upper extremity deformities, among the 3225 cleft patients born during the period 1950-75, and treated in the Finnish Red Cross Cleft Centre is presented. About two-thirds of the patients had an isolated cleft palate--half of the male and nearly all of the female patients. The percentage of upper extremity deformities appearing with the different types of the orofacial clefts was, for clefts of the primary palate 2.0: specifically for cleft lip 0.8, cleft lip--palate 2.6, and cleft lip and palate 3.6; and for clefts of the secondary palate 3.5: specifically for cleft palate 3.7, submucous cleft palate 1.6; and for the branchial arch syndrome (lateral cleft) 5.2; the total average being 2.8 percent. About one-third of the patients were dwarfs, most of them diastrophic dwarfs. Syndactyly was somewhat more common among cleft patients, 0.3%, than in the average population. Polydactyly, 0.1% was about as common as the average. Ectrodactyly was more common among cleft patients, 0.4%, than either syndactyly or polydactyly that are considered the most common hand deformities among the general population. The syndactyly cases were more complicated than the average, among them 4 cases of Apert syndrome were noted. About three-fourths of the 89 patients had multiple deformities.", "contents": "Upper extremity deformities associated with the orofacial clefts. A material of 89 cases of upper extremity deformities, among the 3225 cleft patients born during the period 1950-75, and treated in the Finnish Red Cross Cleft Centre is presented. About two-thirds of the patients had an isolated cleft palate--half of the male and nearly all of the female patients. The percentage of upper extremity deformities appearing with the different types of the orofacial clefts was, for clefts of the primary palate 2.0: specifically for cleft lip 0.8, cleft lip--palate 2.6, and cleft lip and palate 3.6; and for clefts of the secondary palate 3.5: specifically for cleft palate 3.7, submucous cleft palate 1.6; and for the branchial arch syndrome (lateral cleft) 5.2; the total average being 2.8 percent. About one-third of the patients were dwarfs, most of them diastrophic dwarfs. Syndactyly was somewhat more common among cleft patients, 0.3%, than in the average population. Polydactyly, 0.1% was about as common as the average. Ectrodactyly was more common among cleft patients, 0.4%, than either syndactyly or polydactyly that are considered the most common hand deformities among the general population. The syndactyly cases were more complicated than the average, among them 4 cases of Apert syndrome were noted. About three-fourths of the 89 patients had multiple deformities."}
{"id": "PMID:211574", "title": "Morphological significance of associated epithelial cords and ductlike structures in certain tumors of the pancreatic islets.", "content": "The association of epithelial cord cells and ductlike structures in 2 cases of pancreatic islet tumors is presented. The first case was characterized by multiple pancreatic nodes of beta cell insulinoma in a 35-year-old woman. The second case was a Zollinger-Ellison syndrome in a 10-year-old male child with perforated duodenal ulcer due to an islet cell tumor of an aberrant pancreas in the omentrum. Stress is laid upon the striking continuity of the tumorous endocrine and exocrinelike histological formations reproducing the morphological pattern of ducto-insular relationships in histogenesis and islet regeneration.", "contents": "Morphological significance of associated epithelial cords and ductlike structures in certain tumors of the pancreatic islets. The association of epithelial cord cells and ductlike structures in 2 cases of pancreatic islet tumors is presented. The first case was characterized by multiple pancreatic nodes of beta cell insulinoma in a 35-year-old woman. The second case was a Zollinger-Ellison syndrome in a 10-year-old male child with perforated duodenal ulcer due to an islet cell tumor of an aberrant pancreas in the omentrum. Stress is laid upon the striking continuity of the tumorous endocrine and exocrinelike histological formations reproducing the morphological pattern of ducto-insular relationships in histogenesis and islet regeneration."}
{"id": "PMID:211578", "title": "Silicosis in diatomaceous earth factory workers in Sweden.", "content": "Kieselguhr is a greyish-white powder which is made by heating lake ooze containing diatom skeletons to a temperature of about 1000 degrees C. It contains quartz, cristobalite and tridymite. Working with kieselguhr can induce silicosis. In Sweden six cases of silicosis caused by exposure to kieselguhr have been reported to the Worker's Protection Board. The time of exposure was relatively short. New cases have not appeared in the last 20 years. It seems, nevertheless, important to document this unusual form of silicosis, as diatomaceous earth is readily available and the manufacturing process is simple. Demand for kieselguhr has increased and new factories are to be established which may result in new cases of silicosis.", "contents": "Silicosis in diatomaceous earth factory workers in Sweden. Kieselguhr is a greyish-white powder which is made by heating lake ooze containing diatom skeletons to a temperature of about 1000 degrees C. It contains quartz, cristobalite and tridymite. Working with kieselguhr can induce silicosis. In Sweden six cases of silicosis caused by exposure to kieselguhr have been reported to the Worker's Protection Board. The time of exposure was relatively short. New cases have not appeared in the last 20 years. It seems, nevertheless, important to document this unusual form of silicosis, as diatomaceous earth is readily available and the manufacturing process is simple. Demand for kieselguhr has increased and new factories are to be established which may result in new cases of silicosis."}
{"id": "PMID:211579", "title": "Angiotensin-converting enzyme and lysozyme in silicosis and asbestosis.", "content": "Serum angiotensin-converting enzyme (ACE) activity and lysozyme (LZM) concentration in 22 silicosis and 18 asbestosis patients were studied. These patients were compared with 57 untreated and 36 treated sarcoidosis patients. In all groups significantly raised ACE and LZM mean values were noted. Untreated sarcoidosis patients had the highest values. Raised ACE activity in silicosis and asbestosis has not been reported before, and weakens the differential diagnostic value of this enzyme determination for sarcoidosis. The similar patterns of increased ACE and LZM mean values in all three diseases suggest that these enzymes have a common source.", "contents": "Angiotensin-converting enzyme and lysozyme in silicosis and asbestosis. Serum angiotensin-converting enzyme (ACE) activity and lysozyme (LZM) concentration in 22 silicosis and 18 asbestosis patients were studied. These patients were compared with 57 untreated and 36 treated sarcoidosis patients. In all groups significantly raised ACE and LZM mean values were noted. Untreated sarcoidosis patients had the highest values. Raised ACE activity in silicosis and asbestosis has not been reported before, and weakens the differential diagnostic value of this enzyme determination for sarcoidosis. The similar patterns of increased ACE and LZM mean values in all three diseases suggest that these enzymes have a common source."}
{"id": "PMID:211580", "title": "[Incidence and specificity of circulating immune complexes in infectious mononucleosis (proceedings)].", "content": "Occurrence of immune complexes in infectious mononucleosis has been investigated by the 125I Clq binding assay. Increased serum Clq-binding activity was found in 87% of the 23 patients studied during the acute stage of the disease. The serum Clq-binding material detected has properties identical to those of immune complexes. IgG antibodies dissociated from the complexes at acid pH and F (ab)'2 fragments obtained after treatment by pepsin appeared to be directed against the viral capsid antigen of Epstein-Barr virus.", "contents": "[Incidence and specificity of circulating immune complexes in infectious mononucleosis (proceedings)]. Occurrence of immune complexes in infectious mononucleosis has been investigated by the 125I Clq binding assay. Increased serum Clq-binding activity was found in 87% of the 23 patients studied during the acute stage of the disease. The serum Clq-binding material detected has properties identical to those of immune complexes. IgG antibodies dissociated from the complexes at acid pH and F (ab)'2 fragments obtained after treatment by pepsin appeared to be directed against the viral capsid antigen of Epstein-Barr virus."}
{"id": "PMID:211581", "title": "[Induction of glucocorticoid hormone receptors in continuous human T-lymphocyte cultures (proceedings)].", "content": "The presence is documented of high levels of specific glucocorticoid hormone receptors in human cultured T cells (CTC) maintained with a conditioned medium. When conditioned medium was removed from CTC for 24 h, receptor levels reverted to those of fresh, unstimulated lymphocytes. When conditioned medium, or phytohemagglutinin, was then added at various times before testing for glucocorticoid receptors, these stimuli were shown gradually to induce more receptor activity, beginning at about 10 h of stimulation and increasing to 10-fold through 24 h.", "contents": "[Induction of glucocorticoid hormone receptors in continuous human T-lymphocyte cultures (proceedings)]. The presence is documented of high levels of specific glucocorticoid hormone receptors in human cultured T cells (CTC) maintained with a conditioned medium. When conditioned medium was removed from CTC for 24 h, receptor levels reverted to those of fresh, unstimulated lymphocytes. When conditioned medium, or phytohemagglutinin, was then added at various times before testing for glucocorticoid receptors, these stimuli were shown gradually to induce more receptor activity, beginning at about 10 h of stimulation and increasing to 10-fold through 24 h."}
{"id": "PMID:211583", "title": "Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus).", "content": "Owl monkeys were inoculated intracerebrally, subcutaneously, and intravenously with JC, BK, or SV40 virus. Two of four adult owl monkeys inoculated with JC virus, a human polyomavirus, developed brain tumors at 16 and 25 months after inoculation, respectively. A grade 3 to grade 4 astrocytoma (resembling a human glioblastoma multiforme) was found in the left cerebral hemisphere and brainstem of one monkey. The second monkey developed a malignant tumor in the left cerebral hemisphere containing both glial and neuronal cell types. Impression smears prepared from unfixed tissue of this tumor showed cells that contained polyomavirus T antigen. Virion antigens were not detected. Tumor cells cultured in vitro also contained T antigen but were negative for virion antigen. Infectious virus was not isolated from extracts of this tumor.", "contents": "Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus). Owl monkeys were inoculated intracerebrally, subcutaneously, and intravenously with JC, BK, or SV40 virus. Two of four adult owl monkeys inoculated with JC virus, a human polyomavirus, developed brain tumors at 16 and 25 months after inoculation, respectively. A grade 3 to grade 4 astrocytoma (resembling a human glioblastoma multiforme) was found in the left cerebral hemisphere and brainstem of one monkey. The second monkey developed a malignant tumor in the left cerebral hemisphere containing both glial and neuronal cell types. Impression smears prepared from unfixed tissue of this tumor showed cells that contained polyomavirus T antigen. Virion antigens were not detected. Tumor cells cultured in vitro also contained T antigen but were negative for virion antigen. Infectious virus was not isolated from extracts of this tumor."}
{"id": "PMID:211584", "title": "Vitamin D3-induced calcium binding protein in bone tissue.", "content": "As detected by radioimmunoassay with antiserums against chick intestinal calcium binding protein (CaBP), administration of vitamin D3 to rachitic chicks causes a 25- to 100-fold increase in immunoreactive CaBP in chick bone. The bone CaBP has a higher molecular weight (approximately 34,000 daltons) than intestinal CaBP (28,000 daltons), is concentrated principally in the spongiosa and cartilage plate regions of tibia, and responds adaptively to reflect the level of dietary calcium.", "contents": "Vitamin D3-induced calcium binding protein in bone tissue. As detected by radioimmunoassay with antiserums against chick intestinal calcium binding protein (CaBP), administration of vitamin D3 to rachitic chicks causes a 25- to 100-fold increase in immunoreactive CaBP in chick bone. The bone CaBP has a higher molecular weight (approximately 34,000 daltons) than intestinal CaBP (28,000 daltons), is concentrated principally in the spongiosa and cartilage plate regions of tibia, and responds adaptively to reflect the level of dietary calcium."}
{"id": "PMID:211585", "title": "beta-Endorphin is not detectable in plasma from normal human subjects.", "content": "beta-Endorphin is not detectable in plasma from normal human subjects when measured under baseline conditions or after the subjects have received vasopressin, an agent that elevates beta-lipotropin and adrenocorticotropic hormone (ACTH). Significant amounts of beta-endorphin are present in plasma of patients with endocrine disorders associated with increased ACTH and beta-lipotropin production. Highly purified, natural beta-lipotropin is not peripherally converted to beta-endorphin in vivo in normal subjects.", "contents": "beta-Endorphin is not detectable in plasma from normal human subjects. beta-Endorphin is not detectable in plasma from normal human subjects when measured under baseline conditions or after the subjects have received vasopressin, an agent that elevates beta-lipotropin and adrenocorticotropic hormone (ACTH). Significant amounts of beta-endorphin are present in plasma of patients with endocrine disorders associated with increased ACTH and beta-lipotropin production. Highly purified, natural beta-lipotropin is not peripherally converted to beta-endorphin in vivo in normal subjects."}
{"id": "PMID:211586", "title": "Polarity of the blood-brain barrier: neutral amino acid transport into isolated brain capillaries.", "content": "Capillary endothelial cells isolated from rat brain exhibit Na+-dependent uptake of the neutral amino acid analog alpha-(methylamino)isobutyric acid. Since studies in vivo demonstrate that this transport system is not present on the blood side of brain capillaries we conclude that Na+-dependent neutral amino acid transport is located on the brain side. Therefore, the luminal plasma membrane and the antiluminal plasma membrane appear to be functionally distinct. This polarity should permit brain capillary endothelial cells to actively regulate the internal milieu of the brain.", "contents": "Polarity of the blood-brain barrier: neutral amino acid transport into isolated brain capillaries. Capillary endothelial cells isolated from rat brain exhibit Na+-dependent uptake of the neutral amino acid analog alpha-(methylamino)isobutyric acid. Since studies in vivo demonstrate that this transport system is not present on the blood side of brain capillaries we conclude that Na+-dependent neutral amino acid transport is located on the brain side. Therefore, the luminal plasma membrane and the antiluminal plasma membrane appear to be functionally distinct. This polarity should permit brain capillary endothelial cells to actively regulate the internal milieu of the brain."}
{"id": "PMID:211588", "title": "Alkaline phosphatase in Epstein-Barr viral nuclear antigen--positive cell lines.", "content": "The production and nature of alkaline phosphatase were studied in Epstein-Barr viral nuclear antigen-positive, surface membrane immunoglobulin negative-cell lines established from two patients, one with acute myeloid leukemia and one with acute lymphoblastic leukemia. The acute myeloid leukemia-derived cells contained myeloid alkaline phosphatase, while the acute lymphoblastic leukemia-derived cells contained lymphoid alkaline phosphatase. The presence of the myeloid-specific enzyme in a surface membrane immunoglobin--negative cell line suggests that the line is composed of myeloid precursor cells and that such cells may be susceptible to infection with Epstein-Barr virus.", "contents": "Alkaline phosphatase in Epstein-Barr viral nuclear antigen--positive cell lines. The production and nature of alkaline phosphatase were studied in Epstein-Barr viral nuclear antigen-positive, surface membrane immunoglobulin negative-cell lines established from two patients, one with acute myeloid leukemia and one with acute lymphoblastic leukemia. The acute myeloid leukemia-derived cells contained myeloid alkaline phosphatase, while the acute lymphoblastic leukemia-derived cells contained lymphoid alkaline phosphatase. The presence of the myeloid-specific enzyme in a surface membrane immunoglobin--negative cell line suggests that the line is composed of myeloid precursor cells and that such cells may be susceptible to infection with Epstein-Barr virus."}
{"id": "PMID:211589", "title": "Presynaptic alpha-receptor subsensitivity after long-term antidepressant treatment.", "content": "After 3 weeks of twice-daily administration of desipramine to rats, the frequency-response curve for field stimulation of adrenergic neurons in isolated left atrial strips was shifted markedly to the left and the efflux of [3H]norepinephrine was enhanced greatly. After 1 day of treatment, only slight shifts in the frequency-response curve and small increases in [3H]norepinephrine efflux occurred although inhibition of [3H]norepinephrine uptake was already maximal, and phenoxybenzamine caused a further shift to the left in the frequency-response curve similar to that which occurred after 3 weeks of desipramine treatment alone. A gradual decrease in the sensitivity of the presynaptic alpha receptor would explain the delay in the onset of the linical effect of the tricyclic antidepressants.", "contents": "Presynaptic alpha-receptor subsensitivity after long-term antidepressant treatment. After 3 weeks of twice-daily administration of desipramine to rats, the frequency-response curve for field stimulation of adrenergic neurons in isolated left atrial strips was shifted markedly to the left and the efflux of [3H]norepinephrine was enhanced greatly. After 1 day of treatment, only slight shifts in the frequency-response curve and small increases in [3H]norepinephrine efflux occurred although inhibition of [3H]norepinephrine uptake was already maximal, and phenoxybenzamine caused a further shift to the left in the frequency-response curve similar to that which occurred after 3 weeks of desipramine treatment alone. A gradual decrease in the sensitivity of the presynaptic alpha receptor would explain the delay in the onset of the linical effect of the tricyclic antidepressants."}
{"id": "PMID:211590", "title": "[Anti hepatitis A antibodies in the French population and in polyvalent plasma immunoglobulins at a transfusion center (Gamma TS)].", "content": "A search for antibodies directed specifically against hepatitis virus A was carried out in 600 blood donors in the Paris region (354 men and 246 women) by a radio-immunological technic in solid phase. 75.3% had a positive test, no difference was found as regards sex on country of origin (57 were not French). An increase in the frequency of carriers of anti-HAV carriers was observed in relation to age, for 48.4% were aged between 18 and 24 years and 85.9% had antibodies after age 40 years. An estimation of anti-HAV antibodies was made on 19 lots of immunoglobulins from French transfusion centers by the same technic. High and homogenous levels were observed (average 1/4 270). These data were discussed and compared with those in the literature. A better prophylaxis of hepatitis A and the determination of specific activity of polyvalent immunoglobulins with regard to this virus is then considered.", "contents": "[Anti hepatitis A antibodies in the French population and in polyvalent plasma immunoglobulins at a transfusion center (Gamma TS)]. A search for antibodies directed specifically against hepatitis virus A was carried out in 600 blood donors in the Paris region (354 men and 246 women) by a radio-immunological technic in solid phase. 75.3% had a positive test, no difference was found as regards sex on country of origin (57 were not French). An increase in the frequency of carriers of anti-HAV carriers was observed in relation to age, for 48.4% were aged between 18 and 24 years and 85.9% had antibodies after age 40 years. An estimation of anti-HAV antibodies was made on 19 lots of immunoglobulins from French transfusion centers by the same technic. High and homogenous levels were observed (average 1/4 270). These data were discussed and compared with those in the literature. A better prophylaxis of hepatitis A and the determination of specific activity of polyvalent immunoglobulins with regard to this virus is then considered."}
{"id": "PMID:211591", "title": "[Hypercalcemia and biologically active parathyroid hormone].", "content": "Hypercalcaemia always results in serious clinical sequalae and, if not treated, carries a most unfavourable prognosis. The clinician will gain major diagnostic help from an evaluation of the calcitonin and parathyroid hormone blood levels. With regard to parathyroid hormone we have developed, for the first time, a radioimmunoassay which is specific for the estimation of biologically active hormone in the circulation. We are dealing here with an unusual radioimmunological situation as the immunochemical sites are generally quite distinct from those associated with hormonal activity. We are presenting in this first paper the normal values and also the variations that occur in different types of hypercalcaemia. The comparison of these results with those obtained by the usual methods of estimation for parathyroid hormone assay lacking in biological activity shows the value of this new technique.", "contents": "[Hypercalcemia and biologically active parathyroid hormone]. Hypercalcaemia always results in serious clinical sequalae and, if not treated, carries a most unfavourable prognosis. The clinician will gain major diagnostic help from an evaluation of the calcitonin and parathyroid hormone blood levels. With regard to parathyroid hormone we have developed, for the first time, a radioimmunoassay which is specific for the estimation of biologically active hormone in the circulation. We are dealing here with an unusual radioimmunological situation as the immunochemical sites are generally quite distinct from those associated with hormonal activity. We are presenting in this first paper the normal values and also the variations that occur in different types of hypercalcaemia. The comparison of these results with those obtained by the usual methods of estimation for parathyroid hormone assay lacking in biological activity shows the value of this new technique."}
{"id": "PMID:211592", "title": "[Routine biopsy of the liver during tuberculosis in the African adult. 129 cases at Dakar].", "content": "The routine use of needle biopsy of the liver in 129 African patients, aged over 15 years and suffering from various varieties of tuberculosis, gave the following results : specific lesions, above all during miliary tuberculosis, 25,6%, non-specific lesions alone, 37,2% ; normal parenchyma : 37,2%. These result were comparable with those obtained in Europe, in two similar studies, carried only by Coury and al. on pulmonary tuberculosis patients only, an by Mor\u00e8re et al. concerning all forms of tubercuosis. Steatosis without any alcoholic explanation, was observed in 24% of cases. Bacteriological research, even on a culture of liver tissue, was usually disapponting; only one positive result for 34 cultures. This possible spread of tuberculous infection at all stages of its course is still difficult to explain. It leads one to distinguish secondary liver infestations which suggest another localisation of the disease, from liver tuberculosis observed in clinically primary forms.", "contents": "[Routine biopsy of the liver during tuberculosis in the African adult. 129 cases at Dakar]. The routine use of needle biopsy of the liver in 129 African patients, aged over 15 years and suffering from various varieties of tuberculosis, gave the following results : specific lesions, above all during miliary tuberculosis, 25,6%, non-specific lesions alone, 37,2% ; normal parenchyma : 37,2%. These result were comparable with those obtained in Europe, in two similar studies, carried only by Coury and al. on pulmonary tuberculosis patients only, an by Mor\u00e8re et al. concerning all forms of tubercuosis. Steatosis without any alcoholic explanation, was observed in 24% of cases. Bacteriological research, even on a culture of liver tissue, was usually disapponting; only one positive result for 34 cultures. This possible spread of tuberculous infection at all stages of its course is still difficult to explain. It leads one to distinguish secondary liver infestations which suggest another localisation of the disease, from liver tuberculosis observed in clinically primary forms."}
{"id": "PMID:211593", "title": "[The interaction between drugs and oral anticoagulants of the coumarin group].", "content": "The problem of drug interactions during prolonged use of coumarin anticoagulants is important for most patients receiving anticoagulants take several other drugs. Frequent interaction causes either potentialisation of the anticoagulant effect with risk of hemorrhage or inhibition of the anticoagulant effect with risk of thrombosis. The various mechanisms which may explain most interactions are reviewed and the authors propose a list of drugs which should not be administered with coumarin.", "contents": "[The interaction between drugs and oral anticoagulants of the coumarin group]. The problem of drug interactions during prolonged use of coumarin anticoagulants is important for most patients receiving anticoagulants take several other drugs. Frequent interaction causes either potentialisation of the anticoagulant effect with risk of hemorrhage or inhibition of the anticoagulant effect with risk of thrombosis. The various mechanisms which may explain most interactions are reviewed and the authors propose a list of drugs which should not be administered with coumarin."}
{"id": "PMID:211594", "title": "[Opportunistic microbial infections and their importance in general pathology].", "content": "Opportunist germs are commensal bacteria or fungi of the skin and mucosae or saprophytes of the external media, which become virulent when general or local resistance of the organism is lowered. Under the influence of favouring factors, mainly certain drugs, infections due to opportunist germs are becoming more and more frequent, mainly in hospitals, constant or occasional contact of man with these bacteria make diagnosis and prophylaxis of their infections difficult.", "contents": "[Opportunistic microbial infections and their importance in general pathology]. Opportunist germs are commensal bacteria or fungi of the skin and mucosae or saprophytes of the external media, which become virulent when general or local resistance of the organism is lowered. Under the influence of favouring factors, mainly certain drugs, infections due to opportunist germs are becoming more and more frequent, mainly in hospitals, constant or occasional contact of man with these bacteria make diagnosis and prophylaxis of their infections difficult."}
{"id": "PMID:211595", "title": "[Therapeutic use of tiapride in movement disorders].", "content": "Tiapridal was given to twenty-four patients suffering from dyskinesias. Therapeutic efficacity seems to the etiology. Not any fonctitonal improvement was observed in parkinsonism with dyskinesia consecutive to Dopa therapy. On the other hand a good efficacity was found in the treatment of choreas with a quite good tolerance; the functional result will depend of the evolutive state of the disease.", "contents": "[Therapeutic use of tiapride in movement disorders]. Tiapridal was given to twenty-four patients suffering from dyskinesias. Therapeutic efficacity seems to the etiology. Not any fonctitonal improvement was observed in parkinsonism with dyskinesia consecutive to Dopa therapy. On the other hand a good efficacity was found in the treatment of choreas with a quite good tolerance; the functional result will depend of the evolutive state of the disease."}
{"id": "PMID:211596", "title": "[Paget's disease, ankylosing vertebral hyperostosis and hyperostosis frontalis interna].", "content": "Ankylosing vertebral hyperostosis and internal frontal hyperostosis have a frequency of 5% and 8% respectively. In Paget's disease, these two disorders are found with a frequency of 40% and 19.1% respectively. This frequency is not due to chance. There exists a link between the 3 diseases. Ankylosing vertebral hyperostosis is thusa new pathological association in Paget's disease. It is even the most frequent of these associations. It seems Paget's disease induces hyperostosis and not the contrary. The authors suggest the theory that cortical and periostal hypervascularisation in pagetoid bone favour the development of these hyperostoses.", "contents": "[Paget's disease, ankylosing vertebral hyperostosis and hyperostosis frontalis interna]. Ankylosing vertebral hyperostosis and internal frontal hyperostosis have a frequency of 5% and 8% respectively. In Paget's disease, these two disorders are found with a frequency of 40% and 19.1% respectively. This frequency is not due to chance. There exists a link between the 3 diseases. Ankylosing vertebral hyperostosis is thusa new pathological association in Paget's disease. It is even the most frequent of these associations. It seems Paget's disease induces hyperostosis and not the contrary. The authors suggest the theory that cortical and periostal hypervascularisation in pagetoid bone favour the development of these hyperostoses."}
{"id": "PMID:211598", "title": "[Treatment of acute peptic ulcer. Present concept].", "content": "Cimetidine, a powerful inhibitor of acid secretion has produced profound changes in the treatment of acute peptic ulcer. The authors propose a therapeutic attitude takeing into consideration modern knowledge concerning the ulcer patient and his ulcer. After a simplified diagram of the inhibitory mechanisms of acid secretion illustrating the role of the histamine receptors, the various pathogenic routes of treatment are considered with their indications (cimetidine, sulpiride, vagolytics, carbenoxolone). The association of an antacid is useful, except for cimetidine. A choice is necessary in all cases which takes into consideration the patient's interests and the cost of treatment and permits one to avoid pleonasms and illogical treatment. Finally, classical treatment and even milk diet may remain of interest depending on the context of the case.", "contents": "[Treatment of acute peptic ulcer. Present concept]. Cimetidine, a powerful inhibitor of acid secretion has produced profound changes in the treatment of acute peptic ulcer. The authors propose a therapeutic attitude takeing into consideration modern knowledge concerning the ulcer patient and his ulcer. After a simplified diagram of the inhibitory mechanisms of acid secretion illustrating the role of the histamine receptors, the various pathogenic routes of treatment are considered with their indications (cimetidine, sulpiride, vagolytics, carbenoxolone). The association of an antacid is useful, except for cimetidine. A choice is necessary in all cases which takes into consideration the patient's interests and the cost of treatment and permits one to avoid pleonasms and illogical treatment. Finally, classical treatment and even milk diet may remain of interest depending on the context of the case."}
{"id": "PMID:211599", "title": "[Prolonged fever revealing acquired toxoplasmosis in an adult].", "content": "Two cases of acquired toxoplasmosis are reported in 16 and 44 year old patients; prolonged fever was the dominating sign in both cases. It follows from these observations that toxoplasmosis has to be systematically considered as a possible etiology of prolonged fever of undetermined origin.", "contents": "[Prolonged fever revealing acquired toxoplasmosis in an adult]. Two cases of acquired toxoplasmosis are reported in 16 and 44 year old patients; prolonged fever was the dominating sign in both cases. It follows from these observations that toxoplasmosis has to be systematically considered as a possible etiology of prolonged fever of undetermined origin."}
{"id": "PMID:211600", "title": "[Comparative crossover study of tiapride and meprobamate used in agitated states].", "content": "A comparative cross over study of the action of tiapride and meprobamate in behaviour problems with motor and verbal agitation was conducted on 42 hospitalized patients. Tiapride was shown to be statistically superior as far as its efficacy on agitation and its tolerance as it did not modified the patient's vigilance.", "contents": "[Comparative crossover study of tiapride and meprobamate used in agitated states]. A comparative cross over study of the action of tiapride and meprobamate in behaviour problems with motor and verbal agitation was conducted on 42 hospitalized patients. Tiapride was shown to be statistically superior as far as its efficacy on agitation and its tolerance as it did not modified the patient's vigilance."}
{"id": "PMID:211601", "title": "[Alpha heavy chain disease].", "content": "Alpha chain disease is a fairly rare disease (less than 80 cases have been diagnosed to date) the diagnosis of which should be considered as a routine in France when a young arab or oriental jew presents with digestive symptoms such as chronic diarrhoea, abdominal pain of abdominal tumour. The diagnosis of the disease requires two examinations 1) serum immunoelectrophoresis with monospecific anti-IgA antiserum, which alone isolates in 100% of cases the paraprotein. 2) Exploratory laparatomy seems advisable in all cases, for it alone permits multiple lymph node and intestinal biopsies whict are necessary to determine the stage of the disease, the prognosis and treatment. 3) Generally speaking, heavy chain disease seems to represent like Burkitt's lymphoma, a model for experimental carcinoma.", "contents": "[Alpha heavy chain disease]. Alpha chain disease is a fairly rare disease (less than 80 cases have been diagnosed to date) the diagnosis of which should be considered as a routine in France when a young arab or oriental jew presents with digestive symptoms such as chronic diarrhoea, abdominal pain of abdominal tumour. The diagnosis of the disease requires two examinations 1) serum immunoelectrophoresis with monospecific anti-IgA antiserum, which alone isolates in 100% of cases the paraprotein. 2) Exploratory laparatomy seems advisable in all cases, for it alone permits multiple lymph node and intestinal biopsies whict are necessary to determine the stage of the disease, the prognosis and treatment. 3) Generally speaking, heavy chain disease seems to represent like Burkitt's lymphoma, a model for experimental carcinoma."}
{"id": "PMID:211603", "title": "[Duality of dopaminergic receptors. Pharmacologic and clinical perspectives].", "content": "A univocal disorder of dopaminergic activity in the nerve structures responsible for extra-pyramidal motility does not take into account the total phenomena seen in psychomotor neurological studies. The hypothesis of two categories of dopaminergic receptors-respectively excitatory (DA) and inhibitory (DAi)--in the striatal and mesolimbic structures concerned, was derived from experimental and clinical anatomical cytological, and pharmacological data. This duality of the receptors could establish a relationship between dopaminergic mediating, mechanism and adrenergic mediation for with the existence of a least two types of distinct receptors, alpha and beta, has been demonstrated. The author discusses the physiopathology of neuromotor disorders wuch as Parkinson's disease, chorea, and various types of dyskinesias, in relation to this dual mediation. By separation of dopamine antagonists and agonists in this new context, it should be possible to have a more selective approach, which would be better adapted, therefore, for the treatment of these affections. The study of the effects of a new medication, tiapride, on dyskinesias provoked by levodopa in parkinsonian patients, is a step forwards in this new method exploration in neurology.", "contents": "[Duality of dopaminergic receptors. Pharmacologic and clinical perspectives]. A univocal disorder of dopaminergic activity in the nerve structures responsible for extra-pyramidal motility does not take into account the total phenomena seen in psychomotor neurological studies. The hypothesis of two categories of dopaminergic receptors-respectively excitatory (DA) and inhibitory (DAi)--in the striatal and mesolimbic structures concerned, was derived from experimental and clinical anatomical cytological, and pharmacological data. This duality of the receptors could establish a relationship between dopaminergic mediating, mechanism and adrenergic mediation for with the existence of a least two types of distinct receptors, alpha and beta, has been demonstrated. The author discusses the physiopathology of neuromotor disorders wuch as Parkinson's disease, chorea, and various types of dyskinesias, in relation to this dual mediation. By separation of dopamine antagonists and agonists in this new context, it should be possible to have a more selective approach, which would be better adapted, therefore, for the treatment of these affections. The study of the effects of a new medication, tiapride, on dyskinesias provoked by levodopa in parkinsonian patients, is a step forwards in this new method exploration in neurology."}
{"id": "PMID:211604", "title": "[Mononucleosis syndrome and thrombocytopenic purpura in Q fever (Rickettsia burneti)].", "content": "Case of a patient with a mononucleosis syndrome and thrombocytopenic purpura during Q Fever. This etiology could lead to a systematic search for a rickettsial cause for such a symptomatology with a negative Paul-Bunnell-Davidson reaction.", "contents": "[Mononucleosis syndrome and thrombocytopenic purpura in Q fever (Rickettsia burneti)]. Case of a patient with a mononucleosis syndrome and thrombocytopenic purpura during Q Fever. This etiology could lead to a systematic search for a rickettsial cause for such a symptomatology with a negative Paul-Bunnell-Davidson reaction."}
{"id": "PMID:211605", "title": "[Prescribing tiapridal for headache and other painful conditions].", "content": "Tiapridal a new molecule of the benzamide family, raises the pain-threshold level in the mesolimbic system. It has been shown to be effective in 66% of cases of headaches and pain resistant to therapy, and 75% of patients with nausea and vomiting associated with headaches. The average dosage is between 150 and 300 mg or day (1/2 to 1 tablet, 3 times a day). The product is extremely well-tolerated. Somnolence, the most frequent side-effect was noted in 17% of cases. Because of its excellent tolerance it can be prescribed in debilitated patients, alcoholics, and the elderly.", "contents": "[Prescribing tiapridal for headache and other painful conditions]. Tiapridal a new molecule of the benzamide family, raises the pain-threshold level in the mesolimbic system. It has been shown to be effective in 66% of cases of headaches and pain resistant to therapy, and 75% of patients with nausea and vomiting associated with headaches. The average dosage is between 150 and 300 mg or day (1/2 to 1 tablet, 3 times a day). The product is extremely well-tolerated. Somnolence, the most frequent side-effect was noted in 17% of cases. Because of its excellent tolerance it can be prescribed in debilitated patients, alcoholics, and the elderly."}
{"id": "PMID:211607", "title": "[Acute renal failure and consumption coagulopathy in the puerperium].", "content": "Disseminated intravascular coagulation accompanied 18% of cases of acute renal failure during puerperal disorders. We studied in particular 31 cases of disseminated intravascular coagulation with renal failure due to obstetric disorders : 12 post-abortion infections, 3 retentions of a dead foetus, 5 infections, 6 cases of toxemia, 2 retroplacental hemorrhages, two hemorrhages during the third stage, one uremohemolytic syndrome. For diagnosis one relies on the clinical data (bleeding, purpura, shock, hemolysis, visceral involvement) and laboratory data, (coagulation should be supervised throughout the course). The renal lesions are either cortical necrosis, or interstitial nephritis. The analogies with experimental phenomena suggest a human equivalent of the Schwartzmann-Sanarelli syndrome.", "contents": "[Acute renal failure and consumption coagulopathy in the puerperium]. Disseminated intravascular coagulation accompanied 18% of cases of acute renal failure during puerperal disorders. We studied in particular 31 cases of disseminated intravascular coagulation with renal failure due to obstetric disorders : 12 post-abortion infections, 3 retentions of a dead foetus, 5 infections, 6 cases of toxemia, 2 retroplacental hemorrhages, two hemorrhages during the third stage, one uremohemolytic syndrome. For diagnosis one relies on the clinical data (bleeding, purpura, shock, hemolysis, visceral involvement) and laboratory data, (coagulation should be supervised throughout the course). The renal lesions are either cortical necrosis, or interstitial nephritis. The analogies with experimental phenomena suggest a human equivalent of the Schwartzmann-Sanarelli syndrome."}
{"id": "PMID:211608", "title": "[Heat stroke and disseminated intravascular coagulation. Apropos of 2 cases].", "content": "Two cases of fatal heat stroke, concerning a 20 year-old soldier and a 44 year-old psychiatric patient, treated with neuroleptics, are reported. The clinical picture, starting suddenly with coma and hyperthermia, was quite identical for both. Secondarily, while hyperthermia decreases  and the conscience improved partially, an hemorrhagic syndrome similar to a consumption coagulopathy, acute renal insufficiency and acute hepatic failure appear. Death occurred after aggravated neurological disorders and respiratory distress. The anatomical lesions spread on all the viscera include tubular nephritis, and hepatic centro-lobular necrosis and an interstitial and alveolar oedema with hemorrhages and hyaline membranes in the lungs.", "contents": "[Heat stroke and disseminated intravascular coagulation. Apropos of 2 cases]. Two cases of fatal heat stroke, concerning a 20 year-old soldier and a 44 year-old psychiatric patient, treated with neuroleptics, are reported. The clinical picture, starting suddenly with coma and hyperthermia, was quite identical for both. Secondarily, while hyperthermia decreases  and the conscience improved partially, an hemorrhagic syndrome similar to a consumption coagulopathy, acute renal insufficiency and acute hepatic failure appear. Death occurred after aggravated neurological disorders and respiratory distress. The anatomical lesions spread on all the viscera include tubular nephritis, and hepatic centro-lobular necrosis and an interstitial and alveolar oedema with hemorrhages and hyaline membranes in the lungs."}
{"id": "PMID:211609", "title": "[Therapeutic trial of tiapride in ENT].", "content": "Tiapride was studied in 60 patients with ENT affections. The dosage was 1 to 2 ampoules IM a day for 7 to 10 days, followed by a half a tablet 3 to 4 times a day for 2 weeks to 2 months. Results were excellent or good for 16 out of 20 cases of essential headache, 6 out of 6 cases of Barr\u00e9 Li\u00e9ou's syndrome, 7 out 8 cases of sinus pain, 6 out of 8 cases of M\u00e9ni\u00e8's disease, and 6 out of 6 cases of facial paralysis \"a frigore\". In 7 cases of post-concussion syndrome, excellent results were observed in all the patients, on headache. Vertigo was reduced in intensity. The effects was moderate or nil on tinnitus and deafness due to M\u00e9ni\u00e8res syndrome, as well as in 2 casls of facial neuralgia. Tolorance was excellent as, in these 60 patients, only 2 cases of dry mouth and 1 case of vomiting in a diabetic were reported.", "contents": "[Therapeutic trial of tiapride in ENT]. Tiapride was studied in 60 patients with ENT affections. The dosage was 1 to 2 ampoules IM a day for 7 to 10 days, followed by a half a tablet 3 to 4 times a day for 2 weeks to 2 months. Results were excellent or good for 16 out of 20 cases of essential headache, 6 out of 6 cases of Barr\u00e9 Li\u00e9ou's syndrome, 7 out 8 cases of sinus pain, 6 out of 8 cases of M\u00e9ni\u00e8's disease, and 6 out of 6 cases of facial paralysis \"a frigore\". In 7 cases of post-concussion syndrome, excellent results were observed in all the patients, on headache. Vertigo was reduced in intensity. The effects was moderate or nil on tinnitus and deafness due to M\u00e9ni\u00e8res syndrome, as well as in 2 casls of facial neuralgia. Tolorance was excellent as, in these 60 patients, only 2 cases of dry mouth and 1 case of vomiting in a diabetic were reported."}
{"id": "PMID:211610", "title": "[Postoperative medical icterus].", "content": "The onset of jaundice following a surgical operation sometimes raises difficult problems. It is rarely due to hemolysis, infective hepatitis or decomposated cirrhosis of the liver. One should seek as a routine hepatitis due to halotane. However the most frequent cause is \"benign postoperative cholestasis\". This variety of jaundice presents in the form of an icterus due to conjugated bilirubine with often a large increase in alkaline phosphatase levels. The ocurse is variable. Almost always due to severe surgical or septic trauma, accompanied by shock and/or anoxia, it raises difficult diagnostic problems. The clinical and physiopathological aspects of benign postoperative cholestasis are recalled. One should remember, above all, that this is not an autonomous clinical entity but the sign of local or general complications which should be sought carefully.", "contents": "[Postoperative medical icterus]. The onset of jaundice following a surgical operation sometimes raises difficult problems. It is rarely due to hemolysis, infective hepatitis or decomposated cirrhosis of the liver. One should seek as a routine hepatitis due to halotane. However the most frequent cause is \"benign postoperative cholestasis\". This variety of jaundice presents in the form of an icterus due to conjugated bilirubine with often a large increase in alkaline phosphatase levels. The ocurse is variable. Almost always due to severe surgical or septic trauma, accompanied by shock and/or anoxia, it raises difficult diagnostic problems. The clinical and physiopathological aspects of benign postoperative cholestasis are recalled. One should remember, above all, that this is not an autonomous clinical entity but the sign of local or general complications which should be sought carefully."}
{"id": "PMID:211611", "title": "[Study of 13 cases of ostensibly idiopathic male infertility treated successfully by HMG/HCG combination].", "content": "Amoung 95 cases of infertility due to oligo-asthenospermia with normal or low FHS, treated by the association HMG/HCG, 13 cases could be considered a success. From this particularly favourable slries, the author attempts to codify the indications of gonadotrophines in male sterilities. He suggests that such an indication, obvious in case of hypogonadotrophic hypogonadism could be expanded to some normoor hypogonadotrophic hypofertilities.", "contents": "[Study of 13 cases of ostensibly idiopathic male infertility treated successfully by HMG/HCG combination]. Amoung 95 cases of infertility due to oligo-asthenospermia with normal or low FHS, treated by the association HMG/HCG, 13 cases could be considered a success. From this particularly favourable slries, the author attempts to codify the indications of gonadotrophines in male sterilities. He suggests that such an indication, obvious in case of hypogonadotrophic hypogonadism could be expanded to some normoor hypogonadotrophic hypofertilities."}
{"id": "PMID:211612", "title": "[Obesity, hypertension and their relationship in children and adolescents. An epidemiological study in schools (author's transl)].", "content": "In a school population of 532 boys between 10 and 18 years and 287 girls between 10 and 15 years, were drawn up the normal weight height ratios and blood pressures. The frequency of obesity was 6% in both sexes. Girls were more obese than boys. The disease started before the age of 5--6 years. They are frequently familial. A narrow correlation exists between the weight height ratios and blood pressure. The obese patients had in 8 cases a high systolic blood pressure and in 4 cases a high diastolic blood pressure. Half the hypertensive patients were over weight. A strong link between obesity and high blood pressure was also found in the family history. These facts should lead us to treat obesity in children by slimming diets or at least prevent the disease by an appropriate diet. Half the cases of high blood pressure in children and adolescents improved on losing weight.", "contents": "[Obesity, hypertension and their relationship in children and adolescents. An epidemiological study in schools (author's transl)]. In a school population of 532 boys between 10 and 18 years and 287 girls between 10 and 15 years, were drawn up the normal weight height ratios and blood pressures. The frequency of obesity was 6% in both sexes. Girls were more obese than boys. The disease started before the age of 5--6 years. They are frequently familial. A narrow correlation exists between the weight height ratios and blood pressure. The obese patients had in 8 cases a high systolic blood pressure and in 4 cases a high diastolic blood pressure. Half the hypertensive patients were over weight. A strong link between obesity and high blood pressure was also found in the family history. These facts should lead us to treat obesity in children by slimming diets or at least prevent the disease by an appropriate diet. Half the cases of high blood pressure in children and adolescents improved on losing weight."}
{"id": "PMID:211613", "title": "[The lower urinary tract and pseudo-neoplastic sigmoiditis].", "content": "A report is given on the results of 12 radiological explorations of the bladder in 12 patients with pseudo-neoplastic sigmoiditis. In all cases the bladder had an abnormal aspect, in two cases there was a pseudotumor, in two an inflammatory aspect, in four conical attraction of the bladder by the sigmoid. In all 12 cases morphological anomalies of the filled bladder were seen. The ureters were either normal or dilated but without true stenoses. These various aspects may contribute to the differential diagnosis between sigmoiditis and cancer. The differential diagnosis of such vesical lesions is discussed.", "contents": "[The lower urinary tract and pseudo-neoplastic sigmoiditis]. A report is given on the results of 12 radiological explorations of the bladder in 12 patients with pseudo-neoplastic sigmoiditis. In all cases the bladder had an abnormal aspect, in two cases there was a pseudotumor, in two an inflammatory aspect, in four conical attraction of the bladder by the sigmoid. In all 12 cases morphological anomalies of the filled bladder were seen. The ureters were either normal or dilated but without true stenoses. These various aspects may contribute to the differential diagnosis between sigmoiditis and cancer. The differential diagnosis of such vesical lesions is discussed."}
{"id": "PMID:211614", "title": "[An approach to the psychiatric manifestations of alcoholism].", "content": "The authors of this article, confronted with the frequent and common emergencies associated with the \"alcoholic's\" behavioral changes-whether he be a symptomatic drinker, an episodic excessive drinker, or a chronic alcoholic-tested an original molecule belonging to the group of alkylsulfone-0-anisamides (triaprid) on twenty patients hospitalized in a general medical service. The results were very encouraging, showing an improvement of numerous symptoms,in patrticular, tremors, diverse pain, and aggressiveness. The authors note that daily doses of 300 to 400 mg of the modification were well tolerated.", "contents": "[An approach to the psychiatric manifestations of alcoholism]. The authors of this article, confronted with the frequent and common emergencies associated with the \"alcoholic's\" behavioral changes-whether he be a symptomatic drinker, an episodic excessive drinker, or a chronic alcoholic-tested an original molecule belonging to the group of alkylsulfone-0-anisamides (triaprid) on twenty patients hospitalized in a general medical service. The results were very encouraging, showing an improvement of numerous symptoms,in patrticular, tremors, diverse pain, and aggressiveness. The authors note that daily doses of 300 to 400 mg of the modification were well tolerated."}
{"id": "PMID:211615", "title": "[Quantitative study of bacterial flora in operating room air].", "content": "A comparative study of two air-bacteria counting machines, MK II (Casella, London) and R.B. (Joubert, Lyon) was carried out. Pre-operation air samples from operating rooms were drawn by the two machines working simultaneously. The results from the two machines are similar, however the RB machine is more sensitive of the two machines. Moreover, an old operating room without filtrated air had a significantly higher air bacteria contamination (m = 199 +/- 173 bacteria/m3) than a new one with filtrated air (m = 40 +/- 36 bacteria/m3). Samples from laminar air flow (m = 1,3 +/- 1,5 bacteria/m3) were examined as test studies. Working methods and results of air bacteria counts are studied.", "contents": "[Quantitative study of bacterial flora in operating room air]. A comparative study of two air-bacteria counting machines, MK II (Casella, London) and R.B. (Joubert, Lyon) was carried out. Pre-operation air samples from operating rooms were drawn by the two machines working simultaneously. The results from the two machines are similar, however the RB machine is more sensitive of the two machines. Moreover, an old operating room without filtrated air had a significantly higher air bacteria contamination (m = 199 +/- 173 bacteria/m3) than a new one with filtrated air (m = 40 +/- 36 bacteria/m3). Samples from laminar air flow (m = 1,3 +/- 1,5 bacteria/m3) were examined as test studies. Working methods and results of air bacteria counts are studied."}
{"id": "PMID:211616", "title": "[Note concerning the absence of action of tiapride on ocular pressure].", "content": "The effect of tiapride on ocular pressure was evaluated on 24 in-patients divided in to two groups, 12 out of them were suffering from glaucoma, and the other 12 had normal ocular pressure. The dosage was 400 mg daily for 8 days. The ocular pressure was measured two times per day before and during treatment. No significant change in ocular pressure has been observed.", "contents": "[Note concerning the absence of action of tiapride on ocular pressure]. The effect of tiapride on ocular pressure was evaluated on 24 in-patients divided in to two groups, 12 out of them were suffering from glaucoma, and the other 12 had normal ocular pressure. The dosage was 400 mg daily for 8 days. The ocular pressure was measured two times per day before and during treatment. No significant change in ocular pressure has been observed."}
{"id": "PMID:211617", "title": "[Familial carpal tunnel syndrome].", "content": "As the incidence of the carpal tunnel syndrome among family members of patients is not precisely defined in the literature, we described here two new cases. Few authors reporting on patients with the carpal tunnel syndrome refer to the familial occurrence of the disorder. Median nerves were constricted under thickened carpal ligaments. In one case, we looked for amyloidosis in the transverse carpal ligament under electron microscope but we could not find any.", "contents": "[Familial carpal tunnel syndrome]. As the incidence of the carpal tunnel syndrome among family members of patients is not precisely defined in the literature, we described here two new cases. Few authors reporting on patients with the carpal tunnel syndrome refer to the familial occurrence of the disorder. Median nerves were constricted under thickened carpal ligaments. In one case, we looked for amyloidosis in the transverse carpal ligament under electron microscope but we could not find any."}
{"id": "PMID:211618", "title": "[A case of staphylococcal spondylodiscitis after spinal injury. Post-traumatic spondylodiscitis?].", "content": "The authors report the case of a patient who had a D9-D10 staphylococcic spondylodiscitis three month after a fracture of the first lumbar vertebra, which they consider to be posttraumatic despite the fact that it is localised in a different area. They insist on the insufficiency of the literature existing on such cases and on the various pathogenic hypotheses to be applied by the practitionner.", "contents": "[A case of staphylococcal spondylodiscitis after spinal injury. Post-traumatic spondylodiscitis?]. The authors report the case of a patient who had a D9-D10 staphylococcic spondylodiscitis three month after a fracture of the first lumbar vertebra, which they consider to be posttraumatic despite the fact that it is localised in a different area. They insist on the insufficiency of the literature existing on such cases and on the various pathogenic hypotheses to be applied by the practitionner."}
{"id": "PMID:211619", "title": "[Cecum perforation, complication of an acute idiopathic dilatation of the colon, or Ogilvie's syndrome. Practical interest of various pathogenic data. Apropos of one case].", "content": "The authors report a new case of caecal perforation complicating acute dilatation of the colon without organic obstruction (Ogilvie's syndrome). They recall the two characteristics of this syndrome : abdominal distension due to colonic ileus, without any organic cause, and the constant coexistence of an associated pathological condition (traumatic, post-operative, infective, cardio-vascular, respiratory or neurological). The major complication is caecal perforation, announced by a clinical and radiological preperforative syndrome. The pathogenesis of Ogilvie's syndrome remains mysterious. Two facts are worth attention : the role of the sympathetic nerve in intestinal paralysis and the direct intervention of an extra-intestinal pathological factor in the onset of this syndrome. Hence two therapeutic consequences : the favourable effect of splanchnic infiltrations on intestinal motility, and the parallel course of acute colonic dilatation and the extra-intestinal disease.", "contents": "[Cecum perforation, complication of an acute idiopathic dilatation of the colon, or Ogilvie's syndrome. Practical interest of various pathogenic data. Apropos of one case]. The authors report a new case of caecal perforation complicating acute dilatation of the colon without organic obstruction (Ogilvie's syndrome). They recall the two characteristics of this syndrome : abdominal distension due to colonic ileus, without any organic cause, and the constant coexistence of an associated pathological condition (traumatic, post-operative, infective, cardio-vascular, respiratory or neurological). The major complication is caecal perforation, announced by a clinical and radiological preperforative syndrome. The pathogenesis of Ogilvie's syndrome remains mysterious. Two facts are worth attention : the role of the sympathetic nerve in intestinal paralysis and the direct intervention of an extra-intestinal pathological factor in the onset of this syndrome. Hence two therapeutic consequences : the favourable effect of splanchnic infiltrations on intestinal motility, and the parallel course of acute colonic dilatation and the extra-intestinal disease."}
{"id": "PMID:211620", "title": "[Examination of the vulva of small girls. A too often neglected examination].", "content": "After a description of the methods of examination of the vulva, the authors discuss the most important findings. Among the organic diseases, are congenital abnormalities, vulvar coalescence, imperforate hymen, polyps, cysts and above all, trauma. Among the infections, one may note vulvitis or vulvovaginitis but also inclusions, of the clitoridian smaegma, and meatitis. Among the functional disorders, examination of the vulva is necessary for precocius puberty, amenorrhoea, and late puberty. Finally, it permits one to solve a certain number of false problems ; it is however often neglected and should form part of all complete pediatric examinations.", "contents": "[Examination of the vulva of small girls. A too often neglected examination]. After a description of the methods of examination of the vulva, the authors discuss the most important findings. Among the organic diseases, are congenital abnormalities, vulvar coalescence, imperforate hymen, polyps, cysts and above all, trauma. Among the infections, one may note vulvitis or vulvovaginitis but also inclusions, of the clitoridian smaegma, and meatitis. Among the functional disorders, examination of the vulva is necessary for precocius puberty, amenorrhoea, and late puberty. Finally, it permits one to solve a certain number of false problems ; it is however often neglected and should form part of all complete pediatric examinations."}
{"id": "PMID:211621", "title": "[Tiapride in anesthesiology].", "content": "The psycho-motor sedative action of tiapride, which has been demonstrated in internal medicine, was studied in anesthesiology. A group of 253 patients hospitalized for urological (203 cases) or gynaecological (50 cases) operations were given standard premedication together with 100 to 300 mg of tiapride. Preoperative sedation and reduction of anxiety was excellent in 138 cases, moderate in 97 cases, and nil in 18 cases, under the influence of tiapride. Tiapride was perfectly well tolerated even in patients with debility, obesity, alcoholism and cardiac or respiratory insufficiency.", "contents": "[Tiapride in anesthesiology]. The psycho-motor sedative action of tiapride, which has been demonstrated in internal medicine, was studied in anesthesiology. A group of 253 patients hospitalized for urological (203 cases) or gynaecological (50 cases) operations were given standard premedication together with 100 to 300 mg of tiapride. Preoperative sedation and reduction of anxiety was excellent in 138 cases, moderate in 97 cases, and nil in 18 cases, under the influence of tiapride. Tiapride was perfectly well tolerated even in patients with debility, obesity, alcoholism and cardiac or respiratory insufficiency."}
{"id": "PMID:211622", "title": "[Leri's melorheostosis. Apropos of 3 cases in children].", "content": "Three pediatric cases of Leri's melorheostosis are reported. Growth disorders and deformities of the limbs are often the first signs in children. X ray shows areas of very opaque condensation of the long bones parallel to the main axis of the bones parallel to the main axis of the bone, and on the epiphyses, small dense and irregular islets. The course is benign but there may be orthopedic complications.", "contents": "[Leri's melorheostosis. Apropos of 3 cases in children]. Three pediatric cases of Leri's melorheostosis are reported. Growth disorders and deformities of the limbs are often the first signs in children. X ray shows areas of very opaque condensation of the long bones parallel to the main axis of the bones parallel to the main axis of the bone, and on the epiphyses, small dense and irregular islets. The course is benign but there may be orthopedic complications."}
{"id": "PMID:211623", "title": "[Desquamative interstitial pneumonia. Clinical, optic, ultrastructural, histo-immunoligical and enzymatic study of a case].", "content": "The desquamative intersitial pneumonia is a rare, sometimes curable from of diffuse interstitial fibrosis. A clinical, optical and ultrastructural, immunochemical and histo-enzymologic study of one case proved the macrophage nature of the intra-alveolar cells and suggested in the histo-genesis an immunological mechanism depending on lymphocytes.", "contents": "[Desquamative interstitial pneumonia. Clinical, optic, ultrastructural, histo-immunoligical and enzymatic study of a case]. The desquamative intersitial pneumonia is a rare, sometimes curable from of diffuse interstitial fibrosis. A clinical, optical and ultrastructural, immunochemical and histo-enzymologic study of one case proved the macrophage nature of the intra-alveolar cells and suggested in the histo-genesis an immunological mechanism depending on lymphocytes."}
{"id": "PMID:211624", "title": "[Original treatment of headache and migraine].", "content": "Headache and migrain are frequant motives for requesting advice of the general practitioner or specialist. They often participate in a general picture of \"masked depression\". Among the many propounded therapies, a place of choice should be made for Tiapridal, the more so that its antalgic effect is combined with an antiemetic and slightly anticompulsive action.", "contents": "[Original treatment of headache and migraine]. Headache and migrain are frequant motives for requesting advice of the general practitioner or specialist. They often participate in a general picture of \"masked depression\". Among the many propounded therapies, a place of choice should be made for Tiapridal, the more so that its antalgic effect is combined with an antiemetic and slightly anticompulsive action."}
{"id": "PMID:211625", "title": "[Unusual digestive manifestations during rheumatoid purpura. Apropos of 2 cases].", "content": "We have observed two unusual forms of rheumatoid purpura with digestive symptoms in two young girls aged 16 years. In the first case, the signs of complete duodenal stenosis led to a surgical operation which led to the discovery of an infiltrated mesenteric band of adhesions containing numerous lymph nodes, with on the oedematous loops of small intestine, numerous ecchymoses. In the second case, the duodenal-jejunal radiological abnormalities suggested protein-losing enteropathy. especially as this patient like the first, had major hypoproteinemia without albuminuria. The Cr51 radioisotope test confirmed this quite exceptional diagnosis in this disease.", "contents": "[Unusual digestive manifestations during rheumatoid purpura. Apropos of 2 cases]. We have observed two unusual forms of rheumatoid purpura with digestive symptoms in two young girls aged 16 years. In the first case, the signs of complete duodenal stenosis led to a surgical operation which led to the discovery of an infiltrated mesenteric band of adhesions containing numerous lymph nodes, with on the oedematous loops of small intestine, numerous ecchymoses. In the second case, the duodenal-jejunal radiological abnormalities suggested protein-losing enteropathy. especially as this patient like the first, had major hypoproteinemia without albuminuria. The Cr51 radioisotope test confirmed this quite exceptional diagnosis in this disease."}
{"id": "PMID:211626", "title": "[Sinus node dysfunction with conduction disorders and lithium poisoning].", "content": "A case of lithium poisoning with lithium salts in a man of 66 years is reported. Sinus node dysfunction and conduction-tissue modifications were found. The responsibility of lithium in these disoredrs is discussed. The literature and the cellular mode of action of lithium are reviewed.", "contents": "[Sinus node dysfunction with conduction disorders and lithium poisoning]. A case of lithium poisoning with lithium salts in a man of 66 years is reported. Sinus node dysfunction and conduction-tissue modifications were found. The responsibility of lithium in these disoredrs is discussed. The literature and the cellular mode of action of lithium are reviewed."}
{"id": "PMID:211627", "title": "[Alcoholic coma by accidental poisoning in children].", "content": "Among comas of toxic origin, in children, alcoholic coma due to accidental poisoning is uncommon compared with comas due to drugs or household products. It is however important to make an early diagnosis, for this is a severe from of poisoning, liable to cause irreversible cerebral lesions if not treated very quickly. It almost always causes a flask coma, without localising signs, hypothermia and hypoglycemia, but hypoglycemic comas are not always of alcoholic origin, and only measurement of blood alcohol gives a definite diagnosis.", "contents": "[Alcoholic coma by accidental poisoning in children]. Among comas of toxic origin, in children, alcoholic coma due to accidental poisoning is uncommon compared with comas due to drugs or household products. It is however important to make an early diagnosis, for this is a severe from of poisoning, liable to cause irreversible cerebral lesions if not treated very quickly. It almost always causes a flask coma, without localising signs, hypothermia and hypoglycemia, but hypoglycemic comas are not always of alcoholic origin, and only measurement of blood alcohol gives a definite diagnosis."}
{"id": "PMID:211628", "title": "[New therapeutic indications for a dopamine antagonist, Piribedyl].", "content": "Evidence has been found for the view that piribedil stimulates peripheral and central dopamine receptors. Piribedil stimulates the nigro-striatal pathway and has been shown to be an effective antiparkinsonian agent. The stimulation of dopamine receptors in the meso-limbic and/or meso-cortical pathways lead to propose its use in the treatment of affective disorders (maia and depression). Piribedil stimulates dopamine receptors located in the tubero-infundibular pathway and reduces the secretion of prolactine, producing ablactation ; it increases the secretion of STH. Recent studies suggest that the peripheral effects of piribedil, mainly the increases in femoral and cerebral blood flows are also due to stimulation of peripheral dopamine receptors.", "contents": "[New therapeutic indications for a dopamine antagonist, Piribedyl]. Evidence has been found for the view that piribedil stimulates peripheral and central dopamine receptors. Piribedil stimulates the nigro-striatal pathway and has been shown to be an effective antiparkinsonian agent. The stimulation of dopamine receptors in the meso-limbic and/or meso-cortical pathways lead to propose its use in the treatment of affective disorders (maia and depression). Piribedil stimulates dopamine receptors located in the tubero-infundibular pathway and reduces the secretion of prolactine, producing ablactation ; it increases the secretion of STH. Recent studies suggest that the peripheral effects of piribedil, mainly the increases in femoral and cerebral blood flows are also due to stimulation of peripheral dopamine receptors."}
{"id": "PMID:211629", "title": "[3 recent cases of Noonan's syndrome].", "content": "In the present state of our knowledge of cytogenetics, it seems logical to distinguish Noonan's syndrome from Turner's syndrome, thanks to the following arguments: Althought there are minor differences in the morphotype, the small size and the mental retardation are the same in both cases. However there are two lines of evidence: The first, inconstant, concerns the lesser intensity of the gonad changes, especially in the female sex, explaining the relative frequency of the familial forms of the syndrome, of Noonan, which are then trasmitted as autosomic dominants  with variable penetrance. The second, constant and formal until now, concern the chromosome abnormalities. Present in Turner's syndrome, which they help to define in both sexes, they are always absent in Noonan's syndrome, in boys as in girls.", "contents": "[3 recent cases of Noonan's syndrome]. In the present state of our knowledge of cytogenetics, it seems logical to distinguish Noonan's syndrome from Turner's syndrome, thanks to the following arguments: Althought there are minor differences in the morphotype, the small size and the mental retardation are the same in both cases. However there are two lines of evidence: The first, inconstant, concerns the lesser intensity of the gonad changes, especially in the female sex, explaining the relative frequency of the familial forms of the syndrome, of Noonan, which are then trasmitted as autosomic dominants  with variable penetrance. The second, constant and formal until now, concern the chromosome abnormalities. Present in Turner's syndrome, which they help to define in both sexes, they are always absent in Noonan's syndrome, in boys as in girls."}
{"id": "PMID:211630", "title": "[Clinical, bacteriological and pharmacokinetic study of Sisomicin in the newborn infant].", "content": "A study of the efficiency and tolerance of sisomicin in 19 children with severe bacterial infections led to the following conclusions: -sisomicin was efficient, particularly in association with beta-lactamin; -the local and systemic tolerance was good. The susceptibility of various bacterial strains was studied. The half-life of sisomicin given intramuscularly was : 4,0 +/- 1,8 hours in the new-borns under 10 days and 2,0 +/- 0,3 hours in older infants, when creatininemia was below 10 mg/l. No accumulation was found. The recommended daily dose of sisomicin by intramuscular route is 3 to 6 mg/kg, i.e. 1 to 2 mg every 8 hours in infants an 1,5 to 3 mg every 12 hours in new-borns.", "contents": "[Clinical, bacteriological and pharmacokinetic study of Sisomicin in the newborn infant]. A study of the efficiency and tolerance of sisomicin in 19 children with severe bacterial infections led to the following conclusions: -sisomicin was efficient, particularly in association with beta-lactamin; -the local and systemic tolerance was good. The susceptibility of various bacterial strains was studied. The half-life of sisomicin given intramuscularly was : 4,0 +/- 1,8 hours in the new-borns under 10 days and 2,0 +/- 0,3 hours in older infants, when creatininemia was below 10 mg/l. No accumulation was found. The recommended daily dose of sisomicin by intramuscular route is 3 to 6 mg/kg, i.e. 1 to 2 mg every 8 hours in infants an 1,5 to 3 mg every 12 hours in new-borns."}
{"id": "PMID:211632", "title": "[Action of Tiapride on wakefulness].", "content": "A \"blind\" study of the action of tiapride on vigilance was carried out in 3 healthy volunteers using polygraph recordings and psychometric tests. A total of 48 recordings were made in order to study the effects during initial treatment, long-term administration of a dose of 299 mg/day, and the rebound period, we also studied the effect of a single dose of 400 mg of tiapride. No quanlitative or quantitative changes in the polygraph recordings were noted. The psychological tests showed reduction of highest scroes and lowering of the overal efficiency level, but diminished attention during treatment was not observed.", "contents": "[Action of Tiapride on wakefulness]. A \"blind\" study of the action of tiapride on vigilance was carried out in 3 healthy volunteers using polygraph recordings and psychometric tests. A total of 48 recordings were made in order to study the effects during initial treatment, long-term administration of a dose of 299 mg/day, and the rebound period, we also studied the effect of a single dose of 400 mg of tiapride. No quanlitative or quantitative changes in the polygraph recordings were noted. The psychological tests showed reduction of highest scroes and lowering of the overal efficiency level, but diminished attention during treatment was not observed."}
{"id": "PMID:211635", "title": "[Tiapride and alcoholic disorders of central origin. Apropos of 33 cases].", "content": "Thirthy-three alcoholics, aged between 31 and 82 years, were treated for 7 to 30 days with tiapride. The dosage was 600 mg/day (200 mg 3 times daily) by mouth or 100 to 800 mg/day I.M. Out of 27 cases of tremor treated, there were 25 favourable results, one average result and one nil result. Insomnia and character disorders, e.g. anguish, depression, nightmares, hallucinations, were improved during the first few days of treatment in 27 cases out of 30. Out of 12 cases of algo-paresthesia of the lower limb treated, the were 9 good or excellent results, 2 average results and 1 nil result. A favourable result was observed in 7 cases out of nine in vomiting, water brash (3 cases out of 4), and in 16 cases out of 20 in anorexia. No clinical or laboratory disturbance attributable to tiapride was noted in our patients whose general health was often very poor.", "contents": "[Tiapride and alcoholic disorders of central origin. Apropos of 33 cases]. Thirthy-three alcoholics, aged between 31 and 82 years, were treated for 7 to 30 days with tiapride. The dosage was 600 mg/day (200 mg 3 times daily) by mouth or 100 to 800 mg/day I.M. Out of 27 cases of tremor treated, there were 25 favourable results, one average result and one nil result. Insomnia and character disorders, e.g. anguish, depression, nightmares, hallucinations, were improved during the first few days of treatment in 27 cases out of 30. Out of 12 cases of algo-paresthesia of the lower limb treated, the were 9 good or excellent results, 2 average results and 1 nil result. A favourable result was observed in 7 cases out of nine in vomiting, water brash (3 cases out of 4), and in 16 cases out of 20 in anorexia. No clinical or laboratory disturbance attributable to tiapride was noted in our patients whose general health was often very poor."}
{"id": "PMID:211637", "title": "Small cell bronchogenic carcinoma: a distinct clinicopathologic entity.", "content": "Since small cell carcinoma is a treatable disease, with surgery being beneficial in a few cases and with chemotherapy, radiotherapy, and immunotherapy contributing to prolonged survival in patients with inoperable disease, it is essential that the clinical and pathologic features of small cell carcinoma be quickly recognized in a newly presenting patient so that appropriate therapy may be offered.", "contents": "Small cell bronchogenic carcinoma: a distinct clinicopathologic entity. Since small cell carcinoma is a treatable disease, with surgery being beneficial in a few cases and with chemotherapy, radiotherapy, and immunotherapy contributing to prolonged survival in patients with inoperable disease, it is essential that the clinical and pathologic features of small cell carcinoma be quickly recognized in a newly presenting patient so that appropriate therapy may be offered."}
{"id": "PMID:211638", "title": "Clinical biology of small cell carcinoma: relationship to surgical therapy.", "content": "No prognostic factors could be identified that influence survival in patients with small cell carcinoma undergoing traditional therapy. These findings identified small cell carcinoma (1) as a distinct disease entity with reference to non-small cell carcinoma, (2) as a nonsurgical disease, and (3) as a disease demanding systemic treatment.", "contents": "Clinical biology of small cell carcinoma: relationship to surgical therapy. No prognostic factors could be identified that influence survival in patients with small cell carcinoma undergoing traditional therapy. These findings identified small cell carcinoma (1) as a distinct disease entity with reference to non-small cell carcinoma, (2) as a nonsurgical disease, and (3) as a disease demanding systemic treatment."}
{"id": "PMID:211642", "title": "Long-term results in combined-modality treatment of small cell carcinoma of the lung.", "content": "Fifty eight patients with small cell carcinoma of the lung were treated with a combined-modality regimen: chemotherapy with adriamycin, cyclophosphamide, and vincristine; BCG immunotherapy; radiotherapy to the lung primary and prophylactic cranial irradiation. Ninteen patients had limited disease, and 39 had extensive disease. There were 27 (48%) partial remissions and 23 (41%) complete remissions, and median survival was 51 wk. Initial performance status and extent of disease had a definite effect on survival. Only 1 patient developed CNS metastases on prophylactic cranial irradiation. Five of 19 patients (26%) with limited disease remain alive and in complete remission at 26-45+ mo. It is becoming clear from this and other recent studies that we can significantly prolong median survival in small cell lung cancer. However, even more important is the fact that limited-extent small cell lung cancer may be a potentially curable disease.", "contents": "Long-term results in combined-modality treatment of small cell carcinoma of the lung. Fifty eight patients with small cell carcinoma of the lung were treated with a combined-modality regimen: chemotherapy with adriamycin, cyclophosphamide, and vincristine; BCG immunotherapy; radiotherapy to the lung primary and prophylactic cranial irradiation. Ninteen patients had limited disease, and 39 had extensive disease. There were 27 (48%) partial remissions and 23 (41%) complete remissions, and median survival was 51 wk. Initial performance status and extent of disease had a definite effect on survival. Only 1 patient developed CNS metastases on prophylactic cranial irradiation. Five of 19 patients (26%) with limited disease remain alive and in complete remission at 26-45+ mo. It is becoming clear from this and other recent studies that we can significantly prolong median survival in small cell lung cancer. However, even more important is the fact that limited-extent small cell lung cancer may be a potentially curable disease."}
{"id": "PMID:211648", "title": "DNA viruses in urine after renal transplantation.", "content": "Approximately 2 500 specimens from 96 renal transplant recipients were examined for virus particles. Electron microscopy of negatively stained preparations showed that only 3 virus groups were present, namely polyomavirus, adenovirus and herpesvirus. No RNA viruses or oncogenic RNA viruses (retraviridae) were detected. Over a 5-year period polyomavirus was excreted by 37,5% of patients. Both herpesvirus and adenovirus were excreted by approximately 11% of the patients. Although trace quantities of other viruses may have been missed, the absence of RNA virus suggests that immunosuppressive treatment activates these DNA viruses. The failure to detect RNA viruses suggests that they are absent or may require different means of activation.", "contents": "DNA viruses in urine after renal transplantation. Approximately 2 500 specimens from 96 renal transplant recipients were examined for virus particles. Electron microscopy of negatively stained preparations showed that only 3 virus groups were present, namely polyomavirus, adenovirus and herpesvirus. No RNA viruses or oncogenic RNA viruses (retraviridae) were detected. Over a 5-year period polyomavirus was excreted by 37,5% of patients. Both herpesvirus and adenovirus were excreted by approximately 11% of the patients. Although trace quantities of other viruses may have been missed, the absence of RNA virus suggests that immunosuppressive treatment activates these DNA viruses. The failure to detect RNA viruses suggests that they are absent or may require different means of activation."}
{"id": "PMID:211649", "title": "[The rehabilitation of patients with cerebrovascular accidents].", "content": "A rehabilitation programme for patients with cerebrovascular accidents is outlined. The effectiveness of this programme was assessed in 220 patients transfered from Tygerberg Hospital to Goodwood Aftercare Hospital during the past 4 years. They were accepted after the acute phase and when the stroke were completed. The results or rehabilitation were judged by evaluating activities of daily living, namely eating, washing and dressing, and factors such as mobility and use of an affected hand, sphincter control, and ability to communicate. Other factors used to evaluate the rehabilitation programme were complications during treatment and eventual placing of the patient.", "contents": "[The rehabilitation of patients with cerebrovascular accidents]. A rehabilitation programme for patients with cerebrovascular accidents is outlined. The effectiveness of this programme was assessed in 220 patients transfered from Tygerberg Hospital to Goodwood Aftercare Hospital during the past 4 years. They were accepted after the acute phase and when the stroke were completed. The results or rehabilitation were judged by evaluating activities of daily living, namely eating, washing and dressing, and factors such as mobility and use of an affected hand, sphincter control, and ability to communicate. Other factors used to evaluate the rehabilitation programme were complications during treatment and eventual placing of the patient."}
{"id": "PMID:211651", "title": "Metastatic hepatocellular carcinoma of the heart. A case report.", "content": "A metastatic tumour growing in the heart more than 2 years after total removal of the primary hepatic growth is a rare event. Jaundice as a result of bile production by the metastasis is most unusual. The primary tumour did not recur in the regenerated liver. Features which may prove useful in making a clinical diagnosis are briefly considered. Death resulted from a thrombo-embolus from the right atrium lodging in the opening of the tricuspid valve.", "contents": "Metastatic hepatocellular carcinoma of the heart. A case report. A metastatic tumour growing in the heart more than 2 years after total removal of the primary hepatic growth is a rare event. Jaundice as a result of bile production by the metastasis is most unusual. The primary tumour did not recur in the regenerated liver. Features which may prove useful in making a clinical diagnosis are briefly considered. Death resulted from a thrombo-embolus from the right atrium lodging in the opening of the tricuspid valve."}
{"id": "PMID:211652", "title": "Focal dermal hypoplasia (Goltz syndrome): case reports.", "content": "Two Cape Coloured children, both with physical stigmata of Goltz syndrome, are described. Accurate diagnosis of congenital defects in the newborn allows optimal planning of surgical treatment and more accurate prognosis and genetic counselling.", "contents": "Focal dermal hypoplasia (Goltz syndrome): case reports. Two Cape Coloured children, both with physical stigmata of Goltz syndrome, are described. Accurate diagnosis of congenital defects in the newborn allows optimal planning of surgical treatment and more accurate prognosis and genetic counselling."}
{"id": "PMID:211653", "title": "Health needs of geriatric patients discharged from hospital.", "content": "In a survey of the health needs of White and Coloured geriatric patients discharged from hospital it was found that community services were not effectively utilized to meet existing needs. While the White elderly suffered less financial hardship and had better access to medical care, they complained of more symptoms, more loneliness and more depression than their Coloured counterparts.", "contents": "Health needs of geriatric patients discharged from hospital. In a survey of the health needs of White and Coloured geriatric patients discharged from hospital it was found that community services were not effectively utilized to meet existing needs. While the White elderly suffered less financial hardship and had better access to medical care, they complained of more symptoms, more loneliness and more depression than their Coloured counterparts."}
{"id": "PMID:211654", "title": "The radiological features of alcoholic ulcero-osteolytic neuropathy in Blacks.", "content": "The radiological features in the bones and the angiographic changes in the vessels of the lower limbs of 15 chronic alcoholic men are discussed. The distal arteries demonstrate the features of neovascularization. Infective and resorptive changes in the bones of the forefeet are described. These features are related to chronic infection or to the toxic effects of the alcohol.", "contents": "The radiological features of alcoholic ulcero-osteolytic neuropathy in Blacks. The radiological features in the bones and the angiographic changes in the vessels of the lower limbs of 15 chronic alcoholic men are discussed. The distal arteries demonstrate the features of neovascularization. Infective and resorptive changes in the bones of the forefeet are described. These features are related to chronic infection or to the toxic effects of the alcohol."}
{"id": "PMID:211656", "title": "Surgical management of Cushing's syndrome.", "content": "Twenty-seven operations for Cushing's syndrome were reviewed. Included were five cases of adenoma and 22 of adrenal cortical hyperplasia. Preoperative laboratory data, particularly the metyrapone test, were highly accurate in distinguishing adenoma from hyperplasia. Bilateral flank incisions are preferable to the transabdominal approach, with fewer complications, less postoperative ileus, and shorter hospital stays. The inability to inspect both glands simultaneously is of little consequence because biochemical testing data are sufficiently accurate to obviate the need for gross evaluation. The use of perioperative prophylaxis seems to be of importance for preventing thromboembolism in these hypercoagulable patients. The preoperative use of adrenal cortical blocking agents has not proved to yield significant advantages.", "contents": "Surgical management of Cushing's syndrome. Twenty-seven operations for Cushing's syndrome were reviewed. Included were five cases of adenoma and 22 of adrenal cortical hyperplasia. Preoperative laboratory data, particularly the metyrapone test, were highly accurate in distinguishing adenoma from hyperplasia. Bilateral flank incisions are preferable to the transabdominal approach, with fewer complications, less postoperative ileus, and shorter hospital stays. The inability to inspect both glands simultaneously is of little consequence because biochemical testing data are sufficiently accurate to obviate the need for gross evaluation. The use of perioperative prophylaxis seems to be of importance for preventing thromboembolism in these hypercoagulable patients. The preoperative use of adrenal cortical blocking agents has not proved to yield significant advantages."}
{"id": "PMID:211657", "title": "Surgical management of islet-cell adenoma in infancy.", "content": "Persistent neonatal hypoglycemia is a potentially serious condition which should be recognized promptly, investigated thoroughly, and treated expeditiously. Islet-cell adenoma causing hypoglycemia in infancy is very unusual. Only 23 cases have been reported in the literature. This report documents eight cases of our own and summarizes diagnostic methods, proper medical preparation, and fundamental surgical management. Prompt surgical intervention is emphasized, as this will relieve hypoglycemia and may be important in preventing irreversible central nervous system damage. We are of the opinion that any infant with unremitting hypoglycemia, a high corrected insulin/glucose ratio, and failure to respond to maximum diazoxide therapy will require partial pancreatectomy. Identification of the adenoma at the time of operation is unlikely, and blind pancreatectomy and/or reoperation is not unusual.", "contents": "Surgical management of islet-cell adenoma in infancy. Persistent neonatal hypoglycemia is a potentially serious condition which should be recognized promptly, investigated thoroughly, and treated expeditiously. Islet-cell adenoma causing hypoglycemia in infancy is very unusual. Only 23 cases have been reported in the literature. This report documents eight cases of our own and summarizes diagnostic methods, proper medical preparation, and fundamental surgical management. Prompt surgical intervention is emphasized, as this will relieve hypoglycemia and may be important in preventing irreversible central nervous system damage. We are of the opinion that any infant with unremitting hypoglycemia, a high corrected insulin/glucose ratio, and failure to respond to maximum diazoxide therapy will require partial pancreatectomy. Identification of the adenoma at the time of operation is unlikely, and blind pancreatectomy and/or reoperation is not unusual."}
{"id": "PMID:211662", "title": "Possible role of initiation factor activity in the action of interferon.", "content": "Treatment of mouse L cells with homologous interferon results in the production of a protein which inhibits initiation factor activity. Characterization experiments indicate that the interferon in the preparation is responsible for the induction of an inhibitor protein. The impairment of initiation factor activity induced by interferon is specifically reversed by cAMP. An inhibitor protein may be separated from the initiation factor activity by glycerol density gradient sedimentation. The molecular weight of the inhibitor is about 50,000 dalton and sediments with protein kinase activity.", "contents": "Possible role of initiation factor activity in the action of interferon. Treatment of mouse L cells with homologous interferon results in the production of a protein which inhibits initiation factor activity. Characterization experiments indicate that the interferon in the preparation is responsible for the induction of an inhibitor protein. The impairment of initiation factor activity induced by interferon is specifically reversed by cAMP. An inhibitor protein may be separated from the initiation factor activity by glycerol density gradient sedimentation. The molecular weight of the inhibitor is about 50,000 dalton and sediments with protein kinase activity."}
{"id": "PMID:211664", "title": "Effect of interferon on phagocytosis.", "content": "The observation on the in vitro phagocytosis-enhancing effect of mouse interferon has now been confirmed in the same host system and expanded to the human system. Morphological and cytochemical evidence of the activated state of mouse macrophages has also been reported. The interferon-elicited enhanced state of macrophages has been demonstrated in intact animals. The exact mechanism of the macrophage-enhancing effect of interferon remains to be elucidated.", "contents": "Effect of interferon on phagocytosis. The observation on the in vitro phagocytosis-enhancing effect of mouse interferon has now been confirmed in the same host system and expanded to the human system. Morphological and cytochemical evidence of the activated state of mouse macrophages has also been reported. The interferon-elicited enhanced state of macrophages has been demonstrated in intact animals. The exact mechanism of the macrophage-enhancing effect of interferon remains to be elucidated."}
{"id": "PMID:211665", "title": "Effect of interferon on 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": "Effect of interferon on 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:211667", "title": "Effect of interferon on togavirus and arenavirus infections of animals.", "content": "The sensitivity of togaviruses to the effects of IF appears to permit successful exploitation of IF inducers, whereas the relative insensitivity of arenaviruses to IF in vitro appears to correlate with the complete lack of success of poly (ICLC) therapy in the monkey model. Noteworthy is the successful use of poly (ICLC) against fatal encephalitis caused by JE virus in monkeys. Additional studies appear to be warranted to characterize further the role of IF and/or IF inducers in other model infections prior to studies in man.", "contents": "Effect of interferon on togavirus and arenavirus infections of animals. The sensitivity of togaviruses to the effects of IF appears to permit successful exploitation of IF inducers, whereas the relative insensitivity of arenaviruses to IF in vitro appears to correlate with the complete lack of success of poly (ICLC) therapy in the monkey model. Noteworthy is the successful use of poly (ICLC) against fatal encephalitis caused by JE virus in monkeys. Additional studies appear to be warranted to characterize further the role of IF and/or IF inducers in other model infections prior to studies in man."}
{"id": "PMID:211668", "title": "Effect of interferon respiratory infections of animals.", "content": "Several animal models are available for the evaluation of interferon in respiratory virus infections. Considerable variability exists among the respiratory viruses with respect to sensitivity to exogenous interferon or induced endogenous interferon. Due to this apparent variability, combinations of interferon with immune serum and chemotherapeutic agents may provide a means of more efficient control of respiratory infections.", "contents": "Effect of interferon respiratory infections of animals. Several animal models are available for the evaluation of interferon in respiratory virus infections. Considerable variability exists among the respiratory viruses with respect to sensitivity to exogenous interferon or induced endogenous interferon. Due to this apparent variability, combinations of interferon with immune serum and chemotherapeutic agents may provide a means of more efficient control of respiratory infections."}
{"id": "PMID:211670", "title": "Use of interferon in cytomegalovirus infections in man.", "content": "Human CMV is relatively sensitive to the antiviral effects of interferon in vitro. No controlled studies of interferon in human CMV infections have been reported. On the basis of case reports published to date, its usefulness in CMV infections of newborns or transplant recipients is unclear. Double-blind, placebo-controlled studies of interferon prophylaxis against CMV infections in renal transplant recipients are currently underway.", "contents": "Use of interferon in cytomegalovirus infections in man. Human CMV is relatively sensitive to the antiviral effects of interferon in vitro. No controlled studies of interferon in human CMV infections have been reported. On the basis of case reports published to date, its usefulness in CMV infections of newborns or transplant recipients is unclear. Double-blind, placebo-controlled studies of interferon prophylaxis against CMV infections in renal transplant recipients are currently underway."}
{"id": "PMID:211674", "title": "[Control of lymphosarcoma or leukaemia in cats and of feline leukaemia virus (author's transl)].", "content": "A removal programme, specially designed for catteries or multiple cat households, to reduce the incidence of lymphosarcoma or leukaemia in cats and the spread of feline leukaemia virus (FeLV), is discussed. This removal programme includes annual testing of male stud cats, testing all contacts of FeLV-positive cats they had during the past two years, testing cats imported from abroad and isolation--or, if this is not possible, euthanasia--of cats found to be positive for FeLV-antigen. To detect the FeLV-antigen a simple indirect fluorescent antibody technique (FAT) was used to detect FeLV-antigen. During a period of four years, the following results were obtained when a removal programme was carried out by a large cat breeders' association in the Netherlands. The proportion of catteries, in which FeLV-positive cats were found to be present, decreased from 11.5 per cent in the former half of 1974 to 2.1 per cent in the latter half of 1977. The proportion of FeLV-positive cats and male studs decreased from 4.9 per cent to 1.2 per cent and from 5.9 per cent to 1.0 per cent respectively during this period. It is concluded that the recommended removal programme is a simple and successful procedure.", "contents": "[Control of lymphosarcoma or leukaemia in cats and of feline leukaemia virus (author's transl)]. A removal programme, specially designed for catteries or multiple cat households, to reduce the incidence of lymphosarcoma or leukaemia in cats and the spread of feline leukaemia virus (FeLV), is discussed. This removal programme includes annual testing of male stud cats, testing all contacts of FeLV-positive cats they had during the past two years, testing cats imported from abroad and isolation--or, if this is not possible, euthanasia--of cats found to be positive for FeLV-antigen. To detect the FeLV-antigen a simple indirect fluorescent antibody technique (FAT) was used to detect FeLV-antigen. During a period of four years, the following results were obtained when a removal programme was carried out by a large cat breeders' association in the Netherlands. The proportion of catteries, in which FeLV-positive cats were found to be present, decreased from 11.5 per cent in the former half of 1974 to 2.1 per cent in the latter half of 1977. The proportion of FeLV-positive cats and male studs decreased from 4.9 per cent to 1.2 per cent and from 5.9 per cent to 1.0 per cent respectively during this period. It is concluded that the recommended removal programme is a simple and successful procedure."}
{"id": "PMID:211675", "title": "[Results of operative therapy for small-cell bronchogenic carcinoma (author's transl)].", "content": "In considering the results achieved through resection of small-cell bronchogenic carcinoma, the following factors are taken into account: age, localization, staging of the tumor, lymph node involvement, type of resection and adjuvant chemotherapy and radiotherapy. Furthermore, the fate of patients not operated provides a sound basis for comparison with the surgically treated group. In contrast to other authors, these results indicate that small cell carcinomas with limited dissemination have a relatively good prognosis following resection. The cooperative study undertaken in the German Democratic Republic, which included a very large patient collective, resulted in a similar conclusion.", "contents": "[Results of operative therapy for small-cell bronchogenic carcinoma (author's transl)]. In considering the results achieved through resection of small-cell bronchogenic carcinoma, the following factors are taken into account: age, localization, staging of the tumor, lymph node involvement, type of resection and adjuvant chemotherapy and radiotherapy. Furthermore, the fate of patients not operated provides a sound basis for comparison with the surgically treated group. In contrast to other authors, these results indicate that small cell carcinomas with limited dissemination have a relatively good prognosis following resection. The cooperative study undertaken in the German Democratic Republic, which included a very large patient collective, resulted in a similar conclusion."}
{"id": "PMID:211676", "title": "Nature of tyrosinase inactivation in melanosomes.", "content": "The decrease in tyrosinase activity following incubation of melanosomes isolated from mouse melanoma with dopa appeared to be related to the degree of in vitro melanization of melanosomes caused by incubation with dopa. The inactivation similarly occurred in the dopa-tyrosinase reaction system containing ascorbic aicd, although in the presence of ascorbic acid the dopa-quinone is immediately converted back to dopa and therefore melanin formation does not take place. The mode of inactivation of tyrosinase in melanosomes appeared to be similar to the reaction inactivation which is known to occur in the reaction of plant plant tyrosinase. Superoxide anion (O-2) and singlet oxygen (1O2) were estimated but undetectable during the dopa-tyrosinase reaction. Thus the inactivation of tyrosinase is not caused by the reaction products or the oxygen radicals.", "contents": "Nature of tyrosinase inactivation in melanosomes. The decrease in tyrosinase activity following incubation of melanosomes isolated from mouse melanoma with dopa appeared to be related to the degree of in vitro melanization of melanosomes caused by incubation with dopa. The inactivation similarly occurred in the dopa-tyrosinase reaction system containing ascorbic aicd, although in the presence of ascorbic acid the dopa-quinone is immediately converted back to dopa and therefore melanin formation does not take place. The mode of inactivation of tyrosinase in melanosomes appeared to be similar to the reaction inactivation which is known to occur in the reaction of plant plant tyrosinase. Superoxide anion (O-2) and singlet oxygen (1O2) were estimated but undetectable during the dopa-tyrosinase reaction. Thus the inactivation of tyrosinase is not caused by the reaction products or the oxygen radicals."}
{"id": "PMID:211679", "title": "Experimental confirmation in rats of the mixed type proteinuria observed in workers exposed to cadmium.", "content": "Recently we have reported that the proteinuria developed by workers exposed to cadmium was characterized by an increased excretion of high and low molecular weight proteins. These observations were confirmed experimentally. Female rats which were injected intraperitoneally with CdCl2 (1 mg Cd2+/kg) 5 times a week developed after 2 months of treatment a proteinuria qualitatively similar to that observed in workers exposed to cadmium. The analysis of this proteinuria by electrophoresis and gel filtration revealed an increased excretion of low and high molecular weight proteins. This animal study, which confirms previous observations on man, strengthens our hypothesis that the cadmium-induced proteinuria, classically considered as a tubular type proteinuria, is in fact a mixed type proteinuria, involving not only the tubule but also the glomerulus.", "contents": "Experimental confirmation in rats of the mixed type proteinuria observed in workers exposed to cadmium. Recently we have reported that the proteinuria developed by workers exposed to cadmium was characterized by an increased excretion of high and low molecular weight proteins. These observations were confirmed experimentally. Female rats which were injected intraperitoneally with CdCl2 (1 mg Cd2+/kg) 5 times a week developed after 2 months of treatment a proteinuria qualitatively similar to that observed in workers exposed to cadmium. The analysis of this proteinuria by electrophoresis and gel filtration revealed an increased excretion of low and high molecular weight proteins. This animal study, which confirms previous observations on man, strengthens our hypothesis that the cadmium-induced proteinuria, classically considered as a tubular type proteinuria, is in fact a mixed type proteinuria, involving not only the tubule but also the glomerulus."}
{"id": "PMID:211681", "title": "[Investigation of the NAD metabolism in the spleen of patients with Hodgkin's disease (author's transl)].", "content": "A correlation between the NAD metabolism and DNA synthesis, that means cell proliferation, was observed in the course of experimental studies using mouse tissues. The present studies revealed a similar correlation also in splenic tissues of patients with Hodgkin's disease. The enzymatic activities of NAD-pyrophosphorylase and NAD-glycohydrolase were measured in detail in isolated cell nuclei. NAD-pyrophosphorylase activity was particularly increased in patients with Hodgkin's disease. A decrease of enzymatic activity was seen following radiation therapy, and especially 24 hours after local irradiation of the spleen with 200 rd(60Co). These studies are in accordance with former results obtained in mice.", "contents": "[Investigation of the NAD metabolism in the spleen of patients with Hodgkin's disease (author's transl)]. A correlation between the NAD metabolism and DNA synthesis, that means cell proliferation, was observed in the course of experimental studies using mouse tissues. The present studies revealed a similar correlation also in splenic tissues of patients with Hodgkin's disease. The enzymatic activities of NAD-pyrophosphorylase and NAD-glycohydrolase were measured in detail in isolated cell nuclei. NAD-pyrophosphorylase activity was particularly increased in patients with Hodgkin's disease. A decrease of enzymatic activity was seen following radiation therapy, and especially 24 hours after local irradiation of the spleen with 200 rd(60Co). These studies are in accordance with former results obtained in mice."}
{"id": "PMID:211682", "title": "[Comparative electron cytochemical and biochemical study of ATPase and beta-glycerophosphatase activity in thymocytes, leukocytes and erythrocytes].", "content": "A study was made of the effect of procedures (freezing-thawing prior to incubation, prefixation with formaldehyde and glutaraldehyde, incubation with DMSO) on the activity of ATPase and beta-glycerophosphatase in leucocytes and erythrocytes of man, and of the effect of these procedures and of homogenization on ATPase activity in the cells of the rat thymus. The homogenization of rat thymocytes decreases ATPase activity by 15%. A repeated freezing-thawing results in a 15% decrease of ATPase activity in the cells of the rat thymus. The homogenization of rat thymocytes decreases ATPase activity in rat thymocytes, in a 2% decrease in human leucocytes, and in a 21% increase in human erythrocytes. Beta-glycerophosphatase activity in leucocytes and in erythrocytes increases thereby by 89 and 38%. Incorporation of 5% DMSO into the medium increases ATPase activity in human leucocytes and erythrocytes by 17 and 16%, while thymocytes this activity drops by 27%. Beta-glycerophosphatase activity increases thereby in leucocytes by 26 and in erythrocytes by 11.5%, resp.", "contents": "[Comparative electron cytochemical and biochemical study of ATPase and beta-glycerophosphatase activity in thymocytes, leukocytes and erythrocytes]. A study was made of the effect of procedures (freezing-thawing prior to incubation, prefixation with formaldehyde and glutaraldehyde, incubation with DMSO) on the activity of ATPase and beta-glycerophosphatase in leucocytes and erythrocytes of man, and of the effect of these procedures and of homogenization on ATPase activity in the cells of the rat thymus. The homogenization of rat thymocytes decreases ATPase activity by 15%. A repeated freezing-thawing results in a 15% decrease of ATPase activity in the cells of the rat thymus. The homogenization of rat thymocytes decreases ATPase activity in rat thymocytes, in a 2% decrease in human leucocytes, and in a 21% increase in human erythrocytes. Beta-glycerophosphatase activity in leucocytes and in erythrocytes increases thereby by 89 and 38%. Incorporation of 5% DMSO into the medium increases ATPase activity in human leucocytes and erythrocytes by 17 and 16%, while thymocytes this activity drops by 27%. Beta-glycerophosphatase activity increases thereby in leucocytes by 26 and in erythrocytes by 11.5%, resp."}
{"id": "PMID:211683", "title": "[Effect of long-term suppression and long-term stimulation of ACTH secretion on the ultrastructure of tanycytes[].", "content": "The ultrastructure of the tanycyte ependyma in males of Wistar albino rats (160--180 g of weight) was studied under experimental long-term suppression of ACTH secretion and its long-term stimulation. The former effect was accomplished by daily (for 8 days) intraperitoneal administration of dexamethasone phsophate; the stimulation of ACTH secretion was achieved by bilateral adrenalectomy. The long-term suppression of the hypophyseal adrenocorticotrophic function was followed by the ultrastructural markers of an increased transport and secretory activity in the tanycytes (mainly in beta-tanycytes, i. e. the ependyma lining floor of the third ventricle): the increased amount of microvesicles in the Golgi area and in the vicinity of the particular membranous cavity system (MCS, according to the authors' definition), the appearance of some figures of exocytosis, the elevated amount of lipid inclusions. On the contrary, the long-term stimulation of ACTH secretion was followed by the ultrastructural changes of the opposite character. The data obtained are in agreement with the previously established fact that there is a negative correlation between the tanycyte activity and the hypophyseal adrenocorticotrophic activity. It is supposed that this correlation is regulated by a feedback mechanism and attest to the involvement of tanycytes in the inhibitory control of ACTH secretion. A possible substrate inhibiting ACTH secretion by the tanycytes is discussed.", "contents": "[Effect of long-term suppression and long-term stimulation of ACTH secretion on the ultrastructure of tanycytes[]. The ultrastructure of the tanycyte ependyma in males of Wistar albino rats (160--180 g of weight) was studied under experimental long-term suppression of ACTH secretion and its long-term stimulation. The former effect was accomplished by daily (for 8 days) intraperitoneal administration of dexamethasone phsophate; the stimulation of ACTH secretion was achieved by bilateral adrenalectomy. The long-term suppression of the hypophyseal adrenocorticotrophic function was followed by the ultrastructural markers of an increased transport and secretory activity in the tanycytes (mainly in beta-tanycytes, i. e. the ependyma lining floor of the third ventricle): the increased amount of microvesicles in the Golgi area and in the vicinity of the particular membranous cavity system (MCS, according to the authors' definition), the appearance of some figures of exocytosis, the elevated amount of lipid inclusions. On the contrary, the long-term stimulation of ACTH secretion was followed by the ultrastructural changes of the opposite character. The data obtained are in agreement with the previously established fact that there is a negative correlation between the tanycyte activity and the hypophyseal adrenocorticotrophic activity. It is supposed that this correlation is regulated by a feedback mechanism and attest to the involvement of tanycytes in the inhibitory control of ACTH secretion. A possible substrate inhibiting ACTH secretion by the tanycytes is discussed."}
{"id": "PMID:211684", "title": "[Effect of agents disrupting microtubules on the distribution of receptors on the surface of cultured cells].", "content": "Substrate-attached normal mouse fibroblasts, transformed mouse fibroblasts (L-strain) and epithelial cells (MPTR strain) were incubated with two ligands that are cross-linking different group of the surface receptors: concanavalin A and cationic ferritin. Surface-attached ligands were revealed by the indirect immunofluorescent methods. The incubation of control cells with these ligands induced a patching of corresponding surface receptors, and a clearing of these receptors from the surface zones located on the lamellar cytoplasm near the cell edges actively protruding pseudopodia. Effects of three antitubulins (colcemid, colchicine and vinblastin) on the ligand-induced redistribution of receptors were examined and compared with the previously described effects of these drugs on the distribution of active cell edges.", "contents": "[Effect of agents disrupting microtubules on the distribution of receptors on the surface of cultured cells]. Substrate-attached normal mouse fibroblasts, transformed mouse fibroblasts (L-strain) and epithelial cells (MPTR strain) were incubated with two ligands that are cross-linking different group of the surface receptors: concanavalin A and cationic ferritin. Surface-attached ligands were revealed by the indirect immunofluorescent methods. The incubation of control cells with these ligands induced a patching of corresponding surface receptors, and a clearing of these receptors from the surface zones located on the lamellar cytoplasm near the cell edges actively protruding pseudopodia. Effects of three antitubulins (colcemid, colchicine and vinblastin) on the ligand-induced redistribution of receptors were examined and compared with the previously described effects of these drugs on the distribution of active cell edges."}
{"id": "PMID:211689", "title": "[Surgical treatment of malignant neoplasms of the pancreatoduodenal zone].", "content": "The experience with surgical treatment of 866 patients with malignant neoplasms of the pancreato-duodenal zone is analyzed. Radical operations were carried out upon 220 (25.4%) patients, palliative ones-upon 459 (52.8%) and laparotomies-upon 187 (22.7%) patients. The authors draw the conclusion that a one-stage pancreato-duodenal resection is the operation of choice for cancer of the Vater's papilla, distal portion of the common bile duct and of the head of the pancreas. Extended pancreato-duodenal resections with excision of a segment of the portal or the superior mesenteric veins are indicated when adhesion of tumor and the venous wall makes the only contraindication to the radical operation.", "contents": "[Surgical treatment of malignant neoplasms of the pancreatoduodenal zone]. The experience with surgical treatment of 866 patients with malignant neoplasms of the pancreato-duodenal zone is analyzed. Radical operations were carried out upon 220 (25.4%) patients, palliative ones-upon 459 (52.8%) and laparotomies-upon 187 (22.7%) patients. The authors draw the conclusion that a one-stage pancreato-duodenal resection is the operation of choice for cancer of the Vater's papilla, distal portion of the common bile duct and of the head of the pancreas. Extended pancreato-duodenal resections with excision of a segment of the portal or the superior mesenteric veins are indicated when adhesion of tumor and the venous wall makes the only contraindication to the radical operation."}
{"id": "PMID:211695", "title": "Experimental reovirus hepatitis in newborn chicks.", "content": "The avian reovirus \"UM 1-203\" originally isolated in the United States from chickens with tenosynovitis was pathogenic for the newborn chick infected by parenteral inoculation. It induced plurivisceral lesions, which became particularly intense in the liver. The intense local multiplication of the virus provoked a necrotizing hepatitis; viral titers were maintained around an E.I.D.50 of 10(8)/0.2 ml of organ suspension in chicks killed between the 3rd and 5th days after inoculation. As a specific cellular response to the viral multiplication, numerous polykaryocytes formed and increased in number, then regressed and disappeared from the hepatic parenchyma. By histologic and electron microscopic examination at progressive times after infection, the virus was recognizable in the polykaryocyte cytoplasm. In chicks that survived longer (killed the 5th and 6th days after inoculation), regeneration of the hepatic parenchyma occurred and seemed to develop from groups of dense hepatocytes that either lacked the virus or survived the acute phase of infection.", "contents": "Experimental reovirus hepatitis in newborn chicks. The avian reovirus \"UM 1-203\" originally isolated in the United States from chickens with tenosynovitis was pathogenic for the newborn chick infected by parenteral inoculation. It induced plurivisceral lesions, which became particularly intense in the liver. The intense local multiplication of the virus provoked a necrotizing hepatitis; viral titers were maintained around an E.I.D.50 of 10(8)/0.2 ml of organ suspension in chicks killed between the 3rd and 5th days after inoculation. As a specific cellular response to the viral multiplication, numerous polykaryocytes formed and increased in number, then regressed and disappeared from the hepatic parenchyma. By histologic and electron microscopic examination at progressive times after infection, the virus was recognizable in the polykaryocyte cytoplasm. In chicks that survived longer (killed the 5th and 6th days after inoculation), regeneration of the hepatic parenchyma occurred and seemed to develop from groups of dense hepatocytes that either lacked the virus or survived the acute phase of infection."}
{"id": "PMID:211696", "title": "Epizootiology of bovine rotavirus infection.", "content": "Published information on rotaviruses as pathogens, the source of virus infection and the method of transmission of infection under normal conditions are reviewed. The antigenic differences between rotavirus isolates from children, calves, pigs, foals and mice are discussed. Bovine rotaviruses isolated in the USA and the UK were shown to be closely related antigenically and the US vaccine strain protected calves from challenge with the UK rotavirus. Nineteen normally reared calves, with 20 or more ZnSO4 units of serum delta globulin, were susceptible to rotavirus inoculation at two days of age. They developed diarrhoea, showed body weight loss but recovered. Three calves with less than 10 ZnSO4 units of serum delta globulin developed diarrhoea and died. In a serological survey of 654 adult cows and calves from three herds, between 2 per cent and 37 per cent of individuals in a group had low rotavirus antibody titres and were probably susceptible to rotavirus infection. These were found in all age groups of animals studied, whether or not the group had suffered a recent rotavirus epizootic. It was not possible to predict whether an epizootic would develop on the basis of a serological survey.", "contents": "Epizootiology of bovine rotavirus infection. Published information on rotaviruses as pathogens, the source of virus infection and the method of transmission of infection under normal conditions are reviewed. The antigenic differences between rotavirus isolates from children, calves, pigs, foals and mice are discussed. Bovine rotaviruses isolated in the USA and the UK were shown to be closely related antigenically and the US vaccine strain protected calves from challenge with the UK rotavirus. Nineteen normally reared calves, with 20 or more ZnSO4 units of serum delta globulin, were susceptible to rotavirus inoculation at two days of age. They developed diarrhoea, showed body weight loss but recovered. Three calves with less than 10 ZnSO4 units of serum delta globulin developed diarrhoea and died. In a serological survey of 654 adult cows and calves from three herds, between 2 per cent and 37 per cent of individuals in a group had low rotavirus antibody titres and were probably susceptible to rotavirus infection. These were found in all age groups of animals studied, whether or not the group had suffered a recent rotavirus epizootic. It was not possible to predict whether an epizootic would develop on the basis of a serological survey."}
{"id": "PMID:211697", "title": "Antibody titres to lamb rotavirus in colostrum and milk of vaccinated ewes.", "content": "Ewes were vaccinated two to three weeks prior to mating with a formalin-treated preparation of lamb rotavirus. The colostrum and milk produced by vaccinated ewes after the subsequent pregnancy were shown to contain significantly higher titres of antibody to the virus than did mammary secretions from non-vaccinates. The virus neutralising antibody activity was associated with IgG in both colostrum and milk. However, IgG concentrations in the mammary secretions of vaccinates and non-vaccinates did not differ. It is suggested that vaccination of the dam may be of value in protecting the suckled neonatal lamb against rotavirus infection.", "contents": "Antibody titres to lamb rotavirus in colostrum and milk of vaccinated ewes. Ewes were vaccinated two to three weeks prior to mating with a formalin-treated preparation of lamb rotavirus. The colostrum and milk produced by vaccinated ewes after the subsequent pregnancy were shown to contain significantly higher titres of antibody to the virus than did mammary secretions from non-vaccinates. The virus neutralising antibody activity was associated with IgG in both colostrum and milk. However, IgG concentrations in the mammary secretions of vaccinates and non-vaccinates did not differ. It is suggested that vaccination of the dam may be of value in protecting the suckled neonatal lamb against rotavirus infection."}
{"id": "PMID:211699", "title": "Haemorrhagic gastroenteritis in the dog associated with Clostridium welchii.", "content": "Two cases of peracute haemorrhagic enteritis in the dog are reported. Gram-positive bacilli, which were shown in one case to be Clostridium welchii were found adhering to the necrotic epithelial surfaces in parts of the gastrointestinal tract in both cases. Large numbers of C welchii were recovered from the intestines of both dogs.", "contents": "Haemorrhagic gastroenteritis in the dog associated with Clostridium welchii. Two cases of peracute haemorrhagic enteritis in the dog are reported. Gram-positive bacilli, which were shown in one case to be Clostridium welchii were found adhering to the necrotic epithelial surfaces in parts of the gastrointestinal tract in both cases. Large numbers of C welchii were recovered from the intestines of both dogs."}
{"id": "PMID:211700", "title": "A serological survey on the prevalence of infectious bovine rhinotracheitis in Buckinghamshire, Berkshire and Oxfordshire.", "content": "Of the 2368 cattle sera from herds in Buckinghamshire, Berkshire and Oxfordshire examined for infectious bovine rhinotracheitis antibody by an indirect haemagglutination test, 162 (6.8 per cent) proved positive. Positive titres were more prevalent in older cows and they tended to show higher titres. There was little evidence of infection in the bulls tested. The percentage of positive animals in Berkshire and Oxfordshire was 4.7 compared with 10.5 in Buckinghamshire. The infection was not known to be associated with any clinical disease.", "contents": "A serological survey on the prevalence of infectious bovine rhinotracheitis in Buckinghamshire, Berkshire and Oxfordshire. Of the 2368 cattle sera from herds in Buckinghamshire, Berkshire and Oxfordshire examined for infectious bovine rhinotracheitis antibody by an indirect haemagglutination test, 162 (6.8 per cent) proved positive. Positive titres were more prevalent in older cows and they tended to show higher titres. There was little evidence of infection in the bulls tested. The percentage of positive animals in Berkshire and Oxfordshire was 4.7 compared with 10.5 in Buckinghamshire. The infection was not known to be associated with any clinical disease."}
{"id": "PMID:211707", "title": "Investigations on the presence of enteroviruses in drinking water.", "content": "Out of 220 tap-water samples examined, 3.64% were found to contain enteroviruses. The 11 isolates included 3 attenuated poliovirus, 2 Coxsackie A4 and 6 untyped strains. The necessity of improving the treatment of drinking water, especially by disinfection, is outlined.", "contents": "Investigations on the presence of enteroviruses in drinking water. Out of 220 tap-water samples examined, 3.64% were found to contain enteroviruses. The 11 isolates included 3 attenuated poliovirus, 2 Coxsackie A4 and 6 untyped strains. The necessity of improving the treatment of drinking water, especially by disinfection, is outlined."}
{"id": "PMID:211708", "title": "Immunoelectrophoretic study on the host antigens of Sendai virus cultivated in different substrates (embryonated hen eggs and KB cells). Note II. Analysis of KB cell host antigens.", "content": "It could be demonstrated by immunoelectrophoretic analysis that the host antigen incorporated in the envelopes of Sendai virus cultivated in KB cells (Sendai/KB) is characteristic of these cells and does not occur in the envelopes of the same virus grown in the embryonated hen egg (Sendai/egg). This host antigen appears from the first passage in KB cells and is constantly maintained over subsequent passages. The glycoproteins released by Triton X-100 disruption from Sendai/KB envelopes have a concomitant antigenic specificity for both virus and host. In the case of Sendai/egg virus, exclusively virus-specific macromolecules are also released.", "contents": "Immunoelectrophoretic study on the host antigens of Sendai virus cultivated in different substrates (embryonated hen eggs and KB cells). Note II. Analysis of KB cell host antigens. It could be demonstrated by immunoelectrophoretic analysis that the host antigen incorporated in the envelopes of Sendai virus cultivated in KB cells (Sendai/KB) is characteristic of these cells and does not occur in the envelopes of the same virus grown in the embryonated hen egg (Sendai/egg). This host antigen appears from the first passage in KB cells and is constantly maintained over subsequent passages. The glycoproteins released by Triton X-100 disruption from Sendai/KB envelopes have a concomitant antigenic specificity for both virus and host. In the case of Sendai/egg virus, exclusively virus-specific macromolecules are also released."}
{"id": "PMID:211729", "title": "[Pyruvate oxidation and S35-lipoic acid fixation by breast tumor homogenates].", "content": "The rate of pyruvic acid oxidation by human mammary gland tumor homogenates is several times lower compared with that by homogenates of the adjacent non-involved tissues. This dependence is especially manifest with malignant tumors, although in this case both in the involved and non-involved tissues the pyruvate oxidation is slower than in benign tumors. In the in vitro experiments the rate of S35 lipoic acid binding by the precipitated in 10000 g fractions of the homogenates in question was the highest for malignant tumors and 3.36 times lower for the adjacent tissues. In benign tumors these values and their correlation were much more lower.", "contents": "[Pyruvate oxidation and S35-lipoic acid fixation by breast tumor homogenates]. The rate of pyruvic acid oxidation by human mammary gland tumor homogenates is several times lower compared with that by homogenates of the adjacent non-involved tissues. This dependence is especially manifest with malignant tumors, although in this case both in the involved and non-involved tissues the pyruvate oxidation is slower than in benign tumors. In the in vitro experiments the rate of S35 lipoic acid binding by the precipitated in 10000 g fractions of the homogenates in question was the highest for malignant tumors and 3.36 times lower for the adjacent tissues. In benign tumors these values and their correlation were much more lower."}
{"id": "PMID:211731", "title": "[2 aspects of immunity in experimental flavivirus infections].", "content": "Experimentally, two aspects protective and damaging, of the immune response were demonstrated in the course of development of infection in mice inoculated with tickborne encephalitis (TBE) virus, Langat, yellow fever, dengue type 2 or West Nile viruses. The experiments were carried out in animals in which the functions of T- and B-lymphocytes, were temporarily inhibited with cyclophosphane (CP). It was demonstrated that the protective or damaging role of the immune response depended on the method of inoculation of the animals, the virus properties, and characteristics of the mouse strain. The conditions optimal for the development of immunopathological reactions in one infection (TBE) were not identical for those in another infection even when caused by an antigenically related virus (LANGAT). In mice of the AKR strain the possibility of producing a therapeutic effect upon treatment with CP of the animals inoculated with TBE virus was demonstrated.", "contents": "[2 aspects of immunity in experimental flavivirus infections]. Experimentally, two aspects protective and damaging, of the immune response were demonstrated in the course of development of infection in mice inoculated with tickborne encephalitis (TBE) virus, Langat, yellow fever, dengue type 2 or West Nile viruses. The experiments were carried out in animals in which the functions of T- and B-lymphocytes, were temporarily inhibited with cyclophosphane (CP). It was demonstrated that the protective or damaging role of the immune response depended on the method of inoculation of the animals, the virus properties, and characteristics of the mouse strain. The conditions optimal for the development of immunopathological reactions in one infection (TBE) were not identical for those in another infection even when caused by an antigenically related virus (LANGAT). In mice of the AKR strain the possibility of producing a therapeutic effect upon treatment with CP of the animals inoculated with TBE virus was demonstrated."}
{"id": "PMID:211733", "title": "[Enzymatic and ultrastructural changes in isolated liver mitochondria from mice infected with several group A arboviruses].", "content": "Inoculation of white mice of varying body mass with pathologic strains of eastern and Venezuelan equine encephalomyelitis viruses and their attenuated variants (DNC-20/6 and No. 2621), promising as vaccine candidates, resulted in an increase of enzymatic activity and ultrastructural changes of isolated mitochondria from livers of the animals. The attenuated strains of the viruses were shown to induce temporary changes in both aspects of the study which became normal by the end of the study. There was a certain correlational dependence between the enzymatic activity and ultrastructural changes in isolated mitochondria associated with the use of energy in virus reproduction.", "contents": "[Enzymatic and ultrastructural changes in isolated liver mitochondria from mice infected with several group A arboviruses]. Inoculation of white mice of varying body mass with pathologic strains of eastern and Venezuelan equine encephalomyelitis viruses and their attenuated variants (DNC-20/6 and No. 2621), promising as vaccine candidates, resulted in an increase of enzymatic activity and ultrastructural changes of isolated mitochondria from livers of the animals. The attenuated strains of the viruses were shown to induce temporary changes in both aspects of the study which became normal by the end of the study. There was a certain correlational dependence between the enzymatic activity and ultrastructural changes in isolated mitochondria associated with the use of energy in virus reproduction."}
{"id": "PMID:211734", "title": "[Electron microscopic study of the An-750 strain of Powassan virus isolated in the Soviet Union].", "content": "Electron microscopic examinations of brains of white mice inoculated with the An 750 strain isolated for the first time from adult mosquitoes and with the prototype LB strain of Powassan virus were carried out. The method of combination of light and electron microscopy used in the study permitted to compare ultrastructural changes in one cell with the results of light microscopy. Sizes of virions and their localizations in the brain cells were determined. Virus particles were found in large and small neurons as well as in glial elements. Subcellular changes in neurons associated with virus multiplication are described. The causes of differences in sizes of virions measured in ultrathin sections are discussed.", "contents": "[Electron microscopic study of the An-750 strain of Powassan virus isolated in the Soviet Union]. Electron microscopic examinations of brains of white mice inoculated with the An 750 strain isolated for the first time from adult mosquitoes and with the prototype LB strain of Powassan virus were carried out. The method of combination of light and electron microscopy used in the study permitted to compare ultrastructural changes in one cell with the results of light microscopy. Sizes of virions and their localizations in the brain cells were determined. Virus particles were found in large and small neurons as well as in glial elements. Subcellular changes in neurons associated with virus multiplication are described. The causes of differences in sizes of virions measured in ultrathin sections are discussed."}
{"id": "PMID:211742", "title": "[Hormones and cytostatic drugs in cancer chemotherapy].", "content": "From the practical experience the possibilities and the areas of application of the tumour chemotherapy and their value in the complex treatment of tumours are described. After representation of the cytostatic drugs available and description of their principal mechanism of action as well as their clinical pharmacology the indications, side-effects and contraindications for the usual cytostatic drugs are described. The possibilities of the application of the tumour chemotherapy in the clinical and out-patient field are particularly entered. Nowadays, by combinations of several cytostatic drugs and additional application of hormones satisfactory results of therapy may be achieved, which were not yet achievable 10 and more years ago. The proportion of tumours, which may be cured by chemotherapy alone, is still insignificant. The pharmacotherapy of tumours is at present put into earlier stages, e.g. into the postoperative phase as an adjuvant treatment. Finally, some practicable schemata of the therapy for solid forms of tumours are given, which are suitable for use in general practice, without putting in a claim for being regarded as therapy standards.", "contents": "[Hormones and cytostatic drugs in cancer chemotherapy]. From the practical experience the possibilities and the areas of application of the tumour chemotherapy and their value in the complex treatment of tumours are described. After representation of the cytostatic drugs available and description of their principal mechanism of action as well as their clinical pharmacology the indications, side-effects and contraindications for the usual cytostatic drugs are described. The possibilities of the application of the tumour chemotherapy in the clinical and out-patient field are particularly entered. Nowadays, by combinations of several cytostatic drugs and additional application of hormones satisfactory results of therapy may be achieved, which were not yet achievable 10 and more years ago. The proportion of tumours, which may be cured by chemotherapy alone, is still insignificant. The pharmacotherapy of tumours is at present put into earlier stages, e.g. into the postoperative phase as an adjuvant treatment. Finally, some practicable schemata of the therapy for solid forms of tumours are given, which are suitable for use in general practice, without putting in a claim for being regarded as therapy standards."}
{"id": "PMID:211743", "title": "Role of the vagus nerves and catecholamines in the production mechanism of the myocardial failure induced by arteriovenous fistulas.", "content": "Myocardial adenine nucleotides (nicotinamide adenine nucleotides included), glutathione, catecholamines (DOPA, dopamine, noradrenaline, adrenaline) and some enzymes in correlation were investigated in dogs with cardiac failure induced by bilateral iliac arteriovenous fistulas, and unilateral (left) heart vagotomy was also studied for its influence on the changes in the myocardial amounts of these compounds occuring in this pathological circumstance. The cardiac failure in arteriovenous fistula was characterized by the following myocardial metabolic aspects: (I) no change in the amount of proteins (although an important cardiac hypertrophy was present); (II) decreases in the amounts of adenine nucleotides (especially ADP and ATP), without significant variations in the adenosine concentration, accompanied by increases in the concentrations of nicotinamide adenine nucleotides (in both their oxidized and reduced forms) in the heart mitochondria; (III) no change in the amounts of oxidized and reduced glutathione and in the activity of NADH2-dependent glutathione reductase; (IV) a very significant increase in the activity of MAO without significant influences on the levels of the studied catecholamines. The partial vagal denervation of the heart was found to attenuate substantially the changes in the amounts of adenine nucleotides and nicotinamide adenine nucleotides in the myocardial mitochondria and to facilitate the action of MAO on noradrenaline leading to a significant decrease in its myocardial level.", "contents": "Role of the vagus nerves and catecholamines in the production mechanism of the myocardial failure induced by arteriovenous fistulas. Myocardial adenine nucleotides (nicotinamide adenine nucleotides included), glutathione, catecholamines (DOPA, dopamine, noradrenaline, adrenaline) and some enzymes in correlation were investigated in dogs with cardiac failure induced by bilateral iliac arteriovenous fistulas, and unilateral (left) heart vagotomy was also studied for its influence on the changes in the myocardial amounts of these compounds occuring in this pathological circumstance. The cardiac failure in arteriovenous fistula was characterized by the following myocardial metabolic aspects: (I) no change in the amount of proteins (although an important cardiac hypertrophy was present); (II) decreases in the amounts of adenine nucleotides (especially ADP and ATP), without significant variations in the adenosine concentration, accompanied by increases in the concentrations of nicotinamide adenine nucleotides (in both their oxidized and reduced forms) in the heart mitochondria; (III) no change in the amounts of oxidized and reduced glutathione and in the activity of NADH2-dependent glutathione reductase; (IV) a very significant increase in the activity of MAO without significant influences on the levels of the studied catecholamines. The partial vagal denervation of the heart was found to attenuate substantially the changes in the amounts of adenine nucleotides and nicotinamide adenine nucleotides in the myocardial mitochondria and to facilitate the action of MAO on noradrenaline leading to a significant decrease in its myocardial level."}
{"id": "PMID:211744", "title": "The influence of diazepam and thiouracil upon the carcinogenic effect of diethylnitrosamine in gerbils.", "content": "N-diethylnitrosamine (DEN) was simultaneously administered with diazepam (DZP) or thiouracil (TU) once weekly for life to gerbils (Meriones unguiculatus). Additional DZP or TU treatment increased significantly average survival time and inhibited the development of cholangiocarcinomas, although cholangiomas were still observed in these groups. Tumor type and incidence in the nasal cavities were not influenced by DZP or TU. However, in comparison to DEN alone tumor latencies were prolonged.", "contents": "The influence of diazepam and thiouracil upon the carcinogenic effect of diethylnitrosamine in gerbils. N-diethylnitrosamine (DEN) was simultaneously administered with diazepam (DZP) or thiouracil (TU) once weekly for life to gerbils (Meriones unguiculatus). Additional DZP or TU treatment increased significantly average survival time and inhibited the development of cholangiocarcinomas, although cholangiomas were still observed in these groups. Tumor type and incidence in the nasal cavities were not influenced by DZP or TU. However, in comparison to DEN alone tumor latencies were prolonged."}
{"id": "PMID:211745", "title": "[Studies of the activity of various dehydrogenases in the desert rat (Meriones unguiculati) nephrons].", "content": "Researches about the Activity of some Dehydrogenases in the Nephrons of Desert Rats (Meriones unguiculati).--Our desert rats Meriones unguiculati (Mongolian Gerbils) show--also when held under the same experimental conditions as our other laboratory rodents (Wistar rats and white mice)--a somewhat different enzyme histchemical behaviour of these nephrons. The essential difference in the Meriones is that their distal convolutions display on the whole stronger enzyme activities compared as well with the proximal convolutions of the same kidneys, as with the distal convolutions of Wistar rats.", "contents": "[Studies of the activity of various dehydrogenases in the desert rat (Meriones unguiculati) nephrons]. Researches about the Activity of some Dehydrogenases in the Nephrons of Desert Rats (Meriones unguiculati).--Our desert rats Meriones unguiculati (Mongolian Gerbils) show--also when held under the same experimental conditions as our other laboratory rodents (Wistar rats and white mice)--a somewhat different enzyme histchemical behaviour of these nephrons. The essential difference in the Meriones is that their distal convolutions display on the whole stronger enzyme activities compared as well with the proximal convolutions of the same kidneys, as with the distal convolutions of Wistar rats."}
{"id": "PMID:211746", "title": "Morphological and histochemical observations on the intestinal epithelium of Ascardia galli (Nematoda: Ascaridida).", "content": "The intestinal epithelium of Ascardia galli has been studied with various cytological and cytochemical techniques. It consists of large epithelial cells resting on a thick collagenous basal lamina. Their luminal surface is provided with microvilli. The intestinal cells store considerable amounts of glycogen and neutral lipids. Some intracellular granular inclusions, which stain for proteins, phospholipids and lipoproteins, are distributed throughout the cytoplasm. The brush border is composed of microvilli whereas the outer surface coat consists of saliva resistant PAS-positive material. The detailed histochemical analysis of surface material has revealed that it is composed of nonacetylated acid mucopolysaccharides rich in hyaluronic acid with carboxylate polyanions. The brush border shows intense activities of acid phosphatase and glucose-6-phosphatase, moderate of ATPase, and lipase, weak of 5'-nucleotidase. Acid phosphatase-positive intracellular structures are seen in the intestinal epithelium which form distinct aggregations.", "contents": "Morphological and histochemical observations on the intestinal epithelium of Ascardia galli (Nematoda: Ascaridida). The intestinal epithelium of Ascardia galli has been studied with various cytological and cytochemical techniques. It consists of large epithelial cells resting on a thick collagenous basal lamina. Their luminal surface is provided with microvilli. The intestinal cells store considerable amounts of glycogen and neutral lipids. Some intracellular granular inclusions, which stain for proteins, phospholipids and lipoproteins, are distributed throughout the cytoplasm. The brush border is composed of microvilli whereas the outer surface coat consists of saliva resistant PAS-positive material. The detailed histochemical analysis of surface material has revealed that it is composed of nonacetylated acid mucopolysaccharides rich in hyaluronic acid with carboxylate polyanions. The brush border shows intense activities of acid phosphatase and glucose-6-phosphatase, moderate of ATPase, and lipase, weak of 5'-nucleotidase. Acid phosphatase-positive intracellular structures are seen in the intestinal epithelium which form distinct aggregations."}
{"id": "PMID:211747", "title": "Experimental muscular amebiasis in hamsters as a biological model.", "content": "Trophozoites of Entamoeba histolytica maintained in vitro in Pavlova's medium were inoculated by deep intramuscular injection into the proximal left hindleg of hamsters. Thioglycollate medium was utilized as a successful vehicle to induce the infection. The invasion of the muscular tissue by the vegetative forms caused the formation of abscesses with great destruction of muscular fibers. The lesions were limited to the muscular tissue of the femoral area. The number of trophozoites, the medium of thioglycollate as a vehicle, the volume of the inoculum and the trauma caused by the needle were important elements in the evolution of the muscular amebic abscesses. A limited trial of the amebicidal activity of metronidazole utilizing the amebic intramuscular infection was also performed.", "contents": "Experimental muscular amebiasis in hamsters as a biological model. Trophozoites of Entamoeba histolytica maintained in vitro in Pavlova's medium were inoculated by deep intramuscular injection into the proximal left hindleg of hamsters. Thioglycollate medium was utilized as a successful vehicle to induce the infection. The invasion of the muscular tissue by the vegetative forms caused the formation of abscesses with great destruction of muscular fibers. The lesions were limited to the muscular tissue of the femoral area. The number of trophozoites, the medium of thioglycollate as a vehicle, the volume of the inoculum and the trauma caused by the needle were important elements in the evolution of the muscular amebic abscesses. A limited trial of the amebicidal activity of metronidazole utilizing the amebic intramuscular infection was also performed."}
{"id": "PMID:211748", "title": "Morphological, histochemical, and biochemical studies on the gut of Haemonchus contortus Rud., 1803).", "content": "A study has been made on the structure and chemical composition of the gut of Haemonchus contortus (Rud., 1803). The oesophagus has typically a triradiate, cuticle-lined lumen. The intestinal epithelium is provided with a well-developed brush border which contains periodic acid-Schiff-positive mucoproteins. The intestinal epithelium stores glycogen and lipids. It stains diffusely for phospholipids and general proteins and also for terminal-NH2 group. The presence of Fe2+ and Fe3+ containing pigments and activities of acid and alkaline phosphatases, glucose-6-phosphatase, and 5'-nucleotidase have been observed in the intestinal epithelium. Biochemically pH optimum for intestinal acid phosphatase has been found to be 4.8. The brush border shows positive reactions for acid phosphatase and glucose-6-phosphatase, and negative reactions for alkaline phosphatase and 5'-nucleotidase, and negative reactions for alkaline phosphatase and 5'-nucleotidase. The presence of enzymes in the brush border is related to extracellular digestion and absorption of nutrients.", "contents": "Morphological, histochemical, and biochemical studies on the gut of Haemonchus contortus Rud., 1803). A study has been made on the structure and chemical composition of the gut of Haemonchus contortus (Rud., 1803). The oesophagus has typically a triradiate, cuticle-lined lumen. The intestinal epithelium is provided with a well-developed brush border which contains periodic acid-Schiff-positive mucoproteins. The intestinal epithelium stores glycogen and lipids. It stains diffusely for phospholipids and general proteins and also for terminal-NH2 group. The presence of Fe2+ and Fe3+ containing pigments and activities of acid and alkaline phosphatases, glucose-6-phosphatase, and 5'-nucleotidase have been observed in the intestinal epithelium. Biochemically pH optimum for intestinal acid phosphatase has been found to be 4.8. The brush border shows positive reactions for acid phosphatase and glucose-6-phosphatase, and negative reactions for alkaline phosphatase and 5'-nucleotidase, and negative reactions for alkaline phosphatase and 5'-nucleotidase. The presence of enzymes in the brush border is related to extracellular digestion and absorption of nutrients."}
{"id": "PMID:211751", "title": "Cyclic-AMP content in Escherichia coli B/b as affected by N1-(delta 2-isopentyl)adenine.", "content": "N6-(delta 2-isopentenyl)adenine, like other cytokinins, does not detectably modify Escherichia coli growth, but strongly affects cellular levels of cAMP. A substantial delay of the highest level of intracellular cAMP, a reduction to about one half of such maximum level, and a slight increase of cAMP secreted into the medium are reported.", "contents": "Cyclic-AMP content in Escherichia coli B/b as affected by N1-(delta 2-isopentyl)adenine. N6-(delta 2-isopentenyl)adenine, like other cytokinins, does not detectably modify Escherichia coli growth, but strongly affects cellular levels of cAMP. A substantial delay of the highest level of intracellular cAMP, a reduction to about one half of such maximum level, and a slight increase of cAMP secreted into the medium are reported."}
{"id": "PMID:211752", "title": "Further investigations on the antioncogenic activity of A/PR8/34 (HON1)- influenza virus on polyoma virus induced tumors in newborn Wistar rats.", "content": "The oncogenic activity of polyoma virus in newborn Wistar rats can be significantly reduced by simultaneous vaccination with the A/PR8/34 (HON1) strain of influenza virus. The antioncogenic activity (AOA) of influenza virus suspensions was neutralized by the addition of homologous influenza antibodies, indicating that AOA was due to influenza virus and not to any non-viral material possibly present. The AOA of influenza virus was found to decline with storage at 4 degrees C and to depend critically on the relative doses of influenza virus and polyoma virus inoculated per animal. Simultaneous inoculation of animals with influenza and polyoma virus reduced significantly the antibody response to polyoma virus in all experiments, suggesting that influenza virus reduced the multiplication of polyoma virus. By contrast, the antibody response to influenza virus was significantly enhanced by inoculation with polyoma virus in some experiments, only. Influenza virus was found to reduce markedly the adsorption of polyoma virus on rat embryo fibroblast cells, suggesting that AOA could be at least partially due to interference of influenza virus with polyoma virus adsorption on target cells.", "contents": "Further investigations on the antioncogenic activity of A/PR8/34 (HON1)- influenza virus on polyoma virus induced tumors in newborn Wistar rats. The oncogenic activity of polyoma virus in newborn Wistar rats can be significantly reduced by simultaneous vaccination with the A/PR8/34 (HON1) strain of influenza virus. The antioncogenic activity (AOA) of influenza virus suspensions was neutralized by the addition of homologous influenza antibodies, indicating that AOA was due to influenza virus and not to any non-viral material possibly present. The AOA of influenza virus was found to decline with storage at 4 degrees C and to depend critically on the relative doses of influenza virus and polyoma virus inoculated per animal. Simultaneous inoculation of animals with influenza and polyoma virus reduced significantly the antibody response to polyoma virus in all experiments, suggesting that influenza virus reduced the multiplication of polyoma virus. By contrast, the antibody response to influenza virus was significantly enhanced by inoculation with polyoma virus in some experiments, only. Influenza virus was found to reduce markedly the adsorption of polyoma virus on rat embryo fibroblast cells, suggesting that AOA could be at least partially due to interference of influenza virus with polyoma virus adsorption on target cells."}
{"id": "PMID:211753", "title": "[Inactivation of viruses in water by anodic oxidation (author's transl)].", "content": "The inactivating effect of anodic oxidation on viruses performed in an experimental electrolytic polarization unit was investigated with 11 different viruses suspended in tap and superficial water. Furthermore attempts were made to define the influence of factors important in experimental and water respect. Using concentrations up to 10(4) infectious units per ml representing a multiple quantity of the virus demonstrable in contaminated environmental waters all the viruses investigated could be inactivated reliably and rationally when suspended in tap water, more easily however in water of improved conductivity, by passing the current leading unit once. Anodic oxidation represents a fast and rational not denaturating method for decontamination of virus containing waters. Varying conditions of a water as well as bacterial contamination, so far remaining within naturally occurring scope, have only little or no influence on the inactivating effect on viruses. The applicability of the method is discussed briefly.", "contents": "[Inactivation of viruses in water by anodic oxidation (author's transl)]. The inactivating effect of anodic oxidation on viruses performed in an experimental electrolytic polarization unit was investigated with 11 different viruses suspended in tap and superficial water. Furthermore attempts were made to define the influence of factors important in experimental and water respect. Using concentrations up to 10(4) infectious units per ml representing a multiple quantity of the virus demonstrable in contaminated environmental waters all the viruses investigated could be inactivated reliably and rationally when suspended in tap water, more easily however in water of improved conductivity, by passing the current leading unit once. Anodic oxidation represents a fast and rational not denaturating method for decontamination of virus containing waters. Varying conditions of a water as well as bacterial contamination, so far remaining within naturally occurring scope, have only little or no influence on the inactivating effect on viruses. The applicability of the method is discussed briefly."}
{"id": "PMID:211757", "title": "[Results of the research on the preparation and testing of live oral smallpox vaccine in tablet form].", "content": "The authors sum up the results of decade of investigations on the elaboration and trial of live oral smallpox vaccine in tablet form. A conclusion was made that due to mild reactogenic properties, satisfactory immunogenicity and weak allergy producing properties, the mentioned preparation, along with a possibility of express and mass use, can posses future prospects under conditions of final smallpox eradication.", "contents": "[Results of the research on the preparation and testing of live oral smallpox vaccine in tablet form]. The authors sum up the results of decade of investigations on the elaboration and trial of live oral smallpox vaccine in tablet form. A conclusion was made that due to mild reactogenic properties, satisfactory immunogenicity and weak allergy producing properties, the mentioned preparation, along with a possibility of express and mass use, can posses future prospects under conditions of final smallpox eradication."}
{"id": "PMID:211759", "title": "[Experimental study of cellular immunity after administration of inactivated and live virus vaccine].", "content": "Experiments were conducted on guinea pigs with the use of cell migration inhibition test of the peritoneal exudate; stimulation of a definite level of cell immunity in response to the administration of both live and of inactivated vaccine virus was shown. The results obtained are used for the interpretation of the action mechanism of the inactivated preparation in two-stage smallpox vaccination.", "contents": "[Experimental study of cellular immunity after administration of inactivated and live virus vaccine]. Experiments were conducted on guinea pigs with the use of cell migration inhibition test of the peritoneal exudate; stimulation of a definite level of cell immunity in response to the administration of both live and of inactivated vaccine virus was shown. The results obtained are used for the interpretation of the action mechanism of the inactivated preparation in two-stage smallpox vaccination."}
{"id": "PMID:211760", "title": "[Comparative study of lipid A from pertussis microbes differing in the toxicity of their O-antigens. I. Chemical composition and stability of the bond between lipid A and the specific polysaccharide in B. pertussis lipopolysaccharide].", "content": "Data presented in this work indicated that antigens, contrastive by toxicity, obtained by Boiven's method and O'Neill and Tood's method from two strains of Bordetella pertussis differed by stability of lipid A binding with the specific polysaccharide. The influence of duration of the lipopolysaccharide hydrolysis on the fatty acid content in lipid A, and of heptose in the specific polysaccharide was demonstrated. Lipid A fatty acid composition was studied. It is supposed that bound fatty acids are presented as C14 and C19--C22. There was a correlation between the antigen toxicity and the stability of lipid A bond with the specific polysaccharide. Stability of the lipopolysaccharide complex bond depended on heptose and lipid A content and on the composition and the amount of fatty acids in the lipid A preparations.", "contents": "[Comparative study of lipid A from pertussis microbes differing in the toxicity of their O-antigens. I. Chemical composition and stability of the bond between lipid A and the specific polysaccharide in B. pertussis lipopolysaccharide]. Data presented in this work indicated that antigens, contrastive by toxicity, obtained by Boiven's method and O'Neill and Tood's method from two strains of Bordetella pertussis differed by stability of lipid A binding with the specific polysaccharide. The influence of duration of the lipopolysaccharide hydrolysis on the fatty acid content in lipid A, and of heptose in the specific polysaccharide was demonstrated. Lipid A fatty acid composition was studied. It is supposed that bound fatty acids are presented as C14 and C19--C22. There was a correlation between the antigen toxicity and the stability of lipid A bond with the specific polysaccharide. Stability of the lipopolysaccharide complex bond depended on heptose and lipid A content and on the composition and the amount of fatty acids in the lipid A preparations."}
{"id": "PMID:211761", "title": "[Stable paper indicator systems for rapid identification of microorganisms].", "content": "The authors prepared under experimental-industrial conditions paper indicator systems for the express identification of microbes, including carbohydrate discs (by the method of Nikitin et al.), and newly worked out types for the determination of the activity of cytochromoxidase, urease, indol formation, and indicator amino acid decarboxylases (lysin, ornithin, arginine). The use of paper indicator discs proved to be expedient for rationalization of laboratory diagnosis of bacterial intestinal infections.", "contents": "[Stable paper indicator systems for rapid identification of microorganisms]. The authors prepared under experimental-industrial conditions paper indicator systems for the express identification of microbes, including carbohydrate discs (by the method of Nikitin et al.), and newly worked out types for the determination of the activity of cytochromoxidase, urease, indol formation, and indicator amino acid decarboxylases (lysin, ornithin, arginine). The use of paper indicator discs proved to be expedient for rationalization of laboratory diagnosis of bacterial intestinal infections."}
{"id": "PMID:211763", "title": "[Changes in the level of cyclic nucleotides in brain tumors].", "content": "Cyclic 3-5-adenosine-monophosphate and 3-5-guanosinemonophosphate concentrations were studied in the bioptate of brain tumors, examined during neurosurgical operation and in normal brain tissues. The correlations between cyclic nucleotides in the tumors appeared to be significantly decreased in comparison to the intact tissue, being a characteristic signs for all types of tumors. There were significant fluctuations in the level of cyclic nucleotides both in the tumours and nontumorous brain tissues. There were no correlations found between the level of cyclic adenosine-monophosphate and cyclic guanosine-monophosphate on the one hand and the duration of the disease, localization of the tumor, degree of the brain oedema and the type of narcosis on the other.", "contents": "[Changes in the level of cyclic nucleotides in brain tumors]. Cyclic 3-5-adenosine-monophosphate and 3-5-guanosinemonophosphate concentrations were studied in the bioptate of brain tumors, examined during neurosurgical operation and in normal brain tissues. The correlations between cyclic nucleotides in the tumors appeared to be significantly decreased in comparison to the intact tissue, being a characteristic signs for all types of tumors. There were significant fluctuations in the level of cyclic nucleotides both in the tumours and nontumorous brain tissues. There were no correlations found between the level of cyclic adenosine-monophosphate and cyclic guanosine-monophosphate on the one hand and the duration of the disease, localization of the tumor, degree of the brain oedema and the type of narcosis on the other."}
{"id": "PMID:211764", "title": "Studies on adenosine triphosphatase activity of rat cardiac myosin in isoproterenol-induced cardiac hypertrophy.", "content": "Ca2+- and K+ -activated ATPase activity of cardiac myosin from normal and hypertrophied rat hearts was investigated. Cardiac hypertrophy was induced by isoproterenol treatment. A nearly 40% increase in heart mass was seen after seven consecutive days of isoproterenol injection (5 mg/kg) as determined by either heart weight expressed as per cent of body weight or by dry heart weight and total protein content. The measurement of ATP hydrolysis revealed that cardiac myosin from isoproterenol-treated rats had a significant decrease (P less than 0.01) in Ca2+-activated ATPase activity at low ionic strength (0.05 M KCl) in the presence of 5 and 10 mM Ca2+. In contrast, in a high ionic strength medium (0.50 M KCl) the K+- and Ca2+-activated ATPase activity of myosin prepared from hypertrophied myocardium remained unchanged. Comparative analysis of protein present in the light chains of myosin showed no alteration in the proportion of LC1 to LC2 in the myosin from hypertrophied hearts, however, a decrease in the absorption of myosin in the u.v. region was observed. On the basis of our results one can hypothesize that there may be some conformational change in the myosin molecule from hypertrophied myocardium, thereby modifying both Ca2+-sensitivity and ATPase activity at a low KCl concentration.", "contents": "Studies on adenosine triphosphatase activity of rat cardiac myosin in isoproterenol-induced cardiac hypertrophy. Ca2+- and K+ -activated ATPase activity of cardiac myosin from normal and hypertrophied rat hearts was investigated. Cardiac hypertrophy was induced by isoproterenol treatment. A nearly 40% increase in heart mass was seen after seven consecutive days of isoproterenol injection (5 mg/kg) as determined by either heart weight expressed as per cent of body weight or by dry heart weight and total protein content. The measurement of ATP hydrolysis revealed that cardiac myosin from isoproterenol-treated rats had a significant decrease (P less than 0.01) in Ca2+-activated ATPase activity at low ionic strength (0.05 M KCl) in the presence of 5 and 10 mM Ca2+. In contrast, in a high ionic strength medium (0.50 M KCl) the K+- and Ca2+-activated ATPase activity of myosin prepared from hypertrophied myocardium remained unchanged. Comparative analysis of protein present in the light chains of myosin showed no alteration in the proportion of LC1 to LC2 in the myosin from hypertrophied hearts, however, a decrease in the absorption of myosin in the u.v. region was observed. On the basis of our results one can hypothesize that there may be some conformational change in the myosin molecule from hypertrophied myocardium, thereby modifying both Ca2+-sensitivity and ATPase activity at a low KCl concentration."}
{"id": "PMID:211765", "title": "Ultrastructural organization of giant neurones of the mollusc Lymnaea stagnalis under different environmental temperatures.", "content": "The ultrastructure of identified giant neurones of the visceral ring of Lymnaea stagnalis ganglion alters with the seasonal change of the animal and, experimentally, from the inactive physiological state (winter time or at +4 degrees C) to an active one (spring-summer time or at +18 degrees C). The ultrastructural organization of the active animal's neurones is characterized by morphological alteration pointing to an increased metabolic activity, viz., an increased number of nucleoli, an enlarged surface of nuclear membrane and an increase in the nuclear membrane pores, appearance of a zone of free ribosomes near the nuclear membrane, changing the structure of cytosomes, abundant granular endoplasmic reticulum, increase in the number of mitochondria.", "contents": "Ultrastructural organization of giant neurones of the mollusc Lymnaea stagnalis under different environmental temperatures. The ultrastructure of identified giant neurones of the visceral ring of Lymnaea stagnalis ganglion alters with the seasonal change of the animal and, experimentally, from the inactive physiological state (winter time or at +4 degrees C) to an active one (spring-summer time or at +18 degrees C). The ultrastructural organization of the active animal's neurones is characterized by morphological alteration pointing to an increased metabolic activity, viz., an increased number of nucleoli, an enlarged surface of nuclear membrane and an increase in the nuclear membrane pores, appearance of a zone of free ribosomes near the nuclear membrane, changing the structure of cytosomes, abundant granular endoplasmic reticulum, increase in the number of mitochondria."}
{"id": "PMID:211766", "title": "Lysosomal enzyme secretion in rat ventral prostate. Secretagogue action of testosterone and dibutyryl cyclic AMP.", "content": "Rat ventral prostate slices, when incubated in vitro, secrete protein, lysosomal enzymes and newly phosphorylated components in a time- and temperature-dependent manner. Testosterone and dibutyryl cyclic AMP immediately stimulate secretion and 32Pi incorporation. Acid phosphatase and beta-N-acetylhexosaminidase are secreted as acidic isoenzymes presumably contained within primary lysosomes.", "contents": "Lysosomal enzyme secretion in rat ventral prostate. Secretagogue action of testosterone and dibutyryl cyclic AMP. Rat ventral prostate slices, when incubated in vitro, secrete protein, lysosomal enzymes and newly phosphorylated components in a time- and temperature-dependent manner. Testosterone and dibutyryl cyclic AMP immediately stimulate secretion and 32Pi incorporation. Acid phosphatase and beta-N-acetylhexosaminidase are secreted as acidic isoenzymes presumably contained within primary lysosomes."}
{"id": "PMID:211767", "title": "Repeated isologous transplantation of islets of Langerhans in the diabetic rat.", "content": "The metabolic response to repeated isologous transplantation of isolated pancreatic islets was studied in 11 streptozotocin-diabetic AGUS rats. The islets were isolated with collagenase and transplanted intra-portally in batches previously found to be quantitatively insufficient for reversal of the diabetic state. Primary transplantation caused a slight improvement whereas retransplantation with the same number of islets three weeks later was followed by normalization of blood glucose, plasma insulin, urine volume and urine glucose per 24 hours during a three-month observation period. Repeated isologous transplantation of isolated pancreatic islets has an additive effect on the metabolism in that two insufficient tissue doses correct streptozotocin induced diabetes in the rats.", "contents": "Repeated isologous transplantation of islets of Langerhans in the diabetic rat. The metabolic response to repeated isologous transplantation of isolated pancreatic islets was studied in 11 streptozotocin-diabetic AGUS rats. The islets were isolated with collagenase and transplanted intra-portally in batches previously found to be quantitatively insufficient for reversal of the diabetic state. Primary transplantation caused a slight improvement whereas retransplantation with the same number of islets three weeks later was followed by normalization of blood glucose, plasma insulin, urine volume and urine glucose per 24 hours during a three-month observation period. Repeated isologous transplantation of isolated pancreatic islets has an additive effect on the metabolism in that two insufficient tissue doses correct streptozotocin induced diabetes in the rats."}
{"id": "PMID:211774", "title": "Effects of human chorionic gonadotrophin on the release of cyclic AMP and progesterone from the sheep ovary at different stages of the oestrous cycle.", "content": "The rate of release of cyclic AMP by sheep ovaries containing a corpus luteum was determined at different stages of the cycle before and up to 60 min after an intra-arterial (ia) injection of 500 IU human chorionic gonadotrophin (hCG). The median cyclic AMP concentration in arterial plasma and of ovarian venous plasma following hCG stimulation was 93.2 and 98.0 pmol/ml, respectively. The ovaries of ewes examined at Days 1 and 2 of the cycle showed no response to hCG, whereas in 2 sheep at Day 3, hCG caused a slight response, and in 13 sheep examined between Days 5-18, hCG caused a marked increase in cAMP release. In 5 of the sheep in which both ovarian veins were cannulated, only the ovary with a corpus luteum responded to hCG with an increased secretion rate of cyclic AMP and progesterone. The results indicate a lack of responsiveness in the newly formed corpus luteum to hCG.", "contents": "Effects of human chorionic gonadotrophin on the release of cyclic AMP and progesterone from the sheep ovary at different stages of the oestrous cycle. The rate of release of cyclic AMP by sheep ovaries containing a corpus luteum was determined at different stages of the cycle before and up to 60 min after an intra-arterial (ia) injection of 500 IU human chorionic gonadotrophin (hCG). The median cyclic AMP concentration in arterial plasma and of ovarian venous plasma following hCG stimulation was 93.2 and 98.0 pmol/ml, respectively. The ovaries of ewes examined at Days 1 and 2 of the cycle showed no response to hCG, whereas in 2 sheep at Day 3, hCG caused a slight response, and in 13 sheep examined between Days 5-18, hCG caused a marked increase in cAMP release. In 5 of the sheep in which both ovarian veins were cannulated, only the ovary with a corpus luteum responded to hCG with an increased secretion rate of cyclic AMP and progesterone. The results indicate a lack of responsiveness in the newly formed corpus luteum to hCG."}
{"id": "PMID:211775", "title": "Maturational changes in sheep ovarian follicles: gonadotrophic stimulation of cyclic AMP production by isolated theca and granulosa cells.", "content": "Theca and granulosa tissues isolated from sheep ovarian follicles of different sizes were incubated in the presence of human chorionic gonadotrophin (HCG; 5 IU/ml) or follicle stimulating hormone (FSH; 5 microgram NIH-FSH-S11/ml) for 40 min. Changes in the total amounts of cyclic 3',5'-adenosine monophosphate (cAMP) were used as an index of the responsiveness of these preparations to the hormones. Thecal tissue of both large (4-6 mm in diameter) and small (1-3 mm) follicles responded similarly to gonadotrophins. Granulosa cells from small follicles failed to respond to stimulation by HCG. FSH, however, consistently increased cAMP production in comparison with controls or cells treated with HCG. Granulosa cells of large follicles responded to both HCG and FSH.", "contents": "Maturational changes in sheep ovarian follicles: gonadotrophic stimulation of cyclic AMP production by isolated theca and granulosa cells. Theca and granulosa tissues isolated from sheep ovarian follicles of different sizes were incubated in the presence of human chorionic gonadotrophin (HCG; 5 IU/ml) or follicle stimulating hormone (FSH; 5 microgram NIH-FSH-S11/ml) for 40 min. Changes in the total amounts of cyclic 3',5'-adenosine monophosphate (cAMP) were used as an index of the responsiveness of these preparations to the hormones. Thecal tissue of both large (4-6 mm in diameter) and small (1-3 mm) follicles responded similarly to gonadotrophins. Granulosa cells from small follicles failed to respond to stimulation by HCG. FSH, however, consistently increased cAMP production in comparison with controls or cells treated with HCG. Granulosa cells of large follicles responded to both HCG and FSH."}
{"id": "PMID:211776", "title": "Cyclic AMP and cyclic GMP accumulation by isolated hamster granulosa cells stimulated by LH and FSH.", "content": "Cyclic AMP and cyclic GMP accumulation in hamster granulosa cells as a function of gonadotrophin dose (LH or FSH) and time (0-30 min) was determined. The pattern of acute cyclic AMP accumulation was similar in LH and FSH stimulated granulosa cells, except that the cells were more sensitive to FSH than LH. There was a positive dose response relationship of cyclic AMP accumulation in LH and FSH stimulated cells. LH appeared to partially inhibit FSH stimulated cyclic AMP synthesis. Cyclic GMP accumulation was distinctly different in LH and FSH stimulated cells. An inverse dose response relationship of cyclic GMP to dose LH was observed, with only the lowest dose of LH (0.005 IU/ml) stimulating cyclic GMP synthesis. FSH at 0.005 IU/ml did not stimulate cyclic GMP synthesis, but at higher doses generated cyclic GMP in a positive dose-related manner. The results suggest that specificity of hormone action in granulosa cells may be governed in part by differential on cyclic AMP and cyclic GMP in these cells.", "contents": "Cyclic AMP and cyclic GMP accumulation by isolated hamster granulosa cells stimulated by LH and FSH. Cyclic AMP and cyclic GMP accumulation in hamster granulosa cells as a function of gonadotrophin dose (LH or FSH) and time (0-30 min) was determined. The pattern of acute cyclic AMP accumulation was similar in LH and FSH stimulated granulosa cells, except that the cells were more sensitive to FSH than LH. There was a positive dose response relationship of cyclic AMP accumulation in LH and FSH stimulated cells. LH appeared to partially inhibit FSH stimulated cyclic AMP synthesis. Cyclic GMP accumulation was distinctly different in LH and FSH stimulated cells. An inverse dose response relationship of cyclic GMP to dose LH was observed, with only the lowest dose of LH (0.005 IU/ml) stimulating cyclic GMP synthesis. FSH at 0.005 IU/ml did not stimulate cyclic GMP synthesis, but at higher doses generated cyclic GMP in a positive dose-related manner. The results suggest that specificity of hormone action in granulosa cells may be governed in part by differential on cyclic AMP and cyclic GMP in these cells."}
{"id": "PMID:211777", "title": "Calcitonin heterogeneity in lung cancer and medullary thyroid cancer.", "content": "An investigation was made of the increased serum calcitonin in patients with medullary thyroid cancer and bronchogenic carcinoma in order to determine whether these conditions can be differentiated immunochemically. Exdogenous fractions of immunoreactive calcitonin were separated by gel filtration and radioimmunoassayed with calcitonin antibodies having different region specificities. The pattern of serum heterogeneity of patients with medullary thyroid cancer was characterized by the presence of at least seven different fractions of immunoreactive calcitonin, ranging from fraction I (greater than or equal to 30 000 molecular weight (MW) to fraction V (approximately 2500 MW). In contrast, most patients with bronchogenic cancer had a predominance of high MW fractions (i.e. fractions I and IIA). Following in vitro incubation of the serum, the typical MW pattern of bronchogenic cancer serum could be converted to the more diffuse pattern seen in the serum of medullary thyroid cancer. We were able to differentiate, pre-operatively, the hypercalcitonaemia serum of medullary thyroid cancer patients from that of bronchogenic cancer patients by determination of the ratio of calcitonin as radioimmunoassayed with midportion versus carboxyl terminal antibody.", "contents": "Calcitonin heterogeneity in lung cancer and medullary thyroid cancer. An investigation was made of the increased serum calcitonin in patients with medullary thyroid cancer and bronchogenic carcinoma in order to determine whether these conditions can be differentiated immunochemically. Exdogenous fractions of immunoreactive calcitonin were separated by gel filtration and radioimmunoassayed with calcitonin antibodies having different region specificities. The pattern of serum heterogeneity of patients with medullary thyroid cancer was characterized by the presence of at least seven different fractions of immunoreactive calcitonin, ranging from fraction I (greater than or equal to 30 000 molecular weight (MW) to fraction V (approximately 2500 MW). In contrast, most patients with bronchogenic cancer had a predominance of high MW fractions (i.e. fractions I and IIA). Following in vitro incubation of the serum, the typical MW pattern of bronchogenic cancer serum could be converted to the more diffuse pattern seen in the serum of medullary thyroid cancer. We were able to differentiate, pre-operatively, the hypercalcitonaemia serum of medullary thyroid cancer patients from that of bronchogenic cancer patients by determination of the ratio of calcitonin as radioimmunoassayed with midportion versus carboxyl terminal antibody."}
{"id": "PMID:211778", "title": "Clinical studies of \"big ACTH\": its physico-chemical characteristics.", "content": "The big ACTH fractions available from human plasma and pituitary glands and from porcine pituitary glands were physico-chemically characterized by gel filtration, disc electrophoresis and isoelectric separation. In the case of healthy human subjects, big ACTH fractions were isolated by gel filtration from plasma samples taken during states of acute ACTH hypersecretion such as the lysine-8-vasopressin, insulin or metopyrone tests though none of these fractions were isolated from plasma sampled under normal conditions. Even with no stimulation of ACTH secretion, patients with Cushing's disease gave plasma samples that contained an isolable big ACTH fraction, but such a fraction was hardly isolated from plasma taken from patient with Addison's disease. Both human pituitaries and porcine pituitaries contained an isolable big ACTH fraction. By a gel filtration analysis the molecular weight of the big ACTH was estimated to be higher than 20 000. Disc electrophoresis with an acrylamide gel indicated that big ACTH is strongly basic while small ACTH is more acidic than pH 8.3. Isoelectric separation revealed that the isoelectric point of human big ACTH is higher than pH 10.0 while that of small ACTH is about pH 6.8.", "contents": "Clinical studies of \"big ACTH\": its physico-chemical characteristics. The big ACTH fractions available from human plasma and pituitary glands and from porcine pituitary glands were physico-chemically characterized by gel filtration, disc electrophoresis and isoelectric separation. In the case of healthy human subjects, big ACTH fractions were isolated by gel filtration from plasma samples taken during states of acute ACTH hypersecretion such as the lysine-8-vasopressin, insulin or metopyrone tests though none of these fractions were isolated from plasma sampled under normal conditions. Even with no stimulation of ACTH secretion, patients with Cushing's disease gave plasma samples that contained an isolable big ACTH fraction, but such a fraction was hardly isolated from plasma taken from patient with Addison's disease. Both human pituitaries and porcine pituitaries contained an isolable big ACTH fraction. By a gel filtration analysis the molecular weight of the big ACTH was estimated to be higher than 20 000. Disc electrophoresis with an acrylamide gel indicated that big ACTH is strongly basic while small ACTH is more acidic than pH 8.3. Isoelectric separation revealed that the isoelectric point of human big ACTH is higher than pH 10.0 while that of small ACTH is about pH 6.8."}
{"id": "PMID:211779", "title": "Binding of gonadotrophin releasing hormone (GnRH) by bovine anterior pituitary plasma membranes and purified GnRH receptor protein (GnRH.R).", "content": "[125I]-(GnRH) concentration dependence binding curves using isolated bovine anterior pituitary plasma membranes, intact and solubilized, and purified GnRH receptor protein, are compared. In all instances the concentration dependence binding curves had a stepwise character here interpreted as multisigmoid, with several steep increases and plateaus. These curves are compatible with the existence of several binding sites for GnRH. Purification of the GnRH receptor protein (GnRH.R) resulted in about 500 000-fold increase of binding activity and yielded a single protein species on polyacrylamide gel electrophoresis in SDS, of estimated molecular weight 60 000. Similarity of GnRH binding by the purified protein with that of intact and solubilized plasma membranes suggested that a single protein was responsible for the binding in each instance. Thus heterogeneity of GnRH binding is likely attributable to phase transitions of a single receptor protein into different allosteric forms. The data suggest that positive cooperativity is involved in the studied system.", "contents": "Binding of gonadotrophin releasing hormone (GnRH) by bovine anterior pituitary plasma membranes and purified GnRH receptor protein (GnRH.R). [125I]-(GnRH) concentration dependence binding curves using isolated bovine anterior pituitary plasma membranes, intact and solubilized, and purified GnRH receptor protein, are compared. In all instances the concentration dependence binding curves had a stepwise character here interpreted as multisigmoid, with several steep increases and plateaus. These curves are compatible with the existence of several binding sites for GnRH. Purification of the GnRH receptor protein (GnRH.R) resulted in about 500 000-fold increase of binding activity and yielded a single protein species on polyacrylamide gel electrophoresis in SDS, of estimated molecular weight 60 000. Similarity of GnRH binding by the purified protein with that of intact and solubilized plasma membranes suggested that a single protein was responsible for the binding in each instance. Thus heterogeneity of GnRH binding is likely attributable to phase transitions of a single receptor protein into different allosteric forms. The data suggest that positive cooperativity is involved in the studied system."}
{"id": "PMID:211780", "title": "Action of KI and several iodocompounds on [3H]uridine incorporation into thyroid RNA.", "content": "The present studies were performed in order to further clarify the action of iodine and iodocompounds on the incorporation of labelled uridine into thyroid RNA. KI decreased RNA labelling but did not alter total [3H]uridine uptake or [3H]inulin distribution space. KI also inhibited the increase in RNA labelling produced by 8 mM glucose. T4 was more potent on a molar basis than KI in impairing uridine incorporation. TETRAC, TRIAC and isopropyl-T3 also decreased RNA labelling, while T2 and isopropyl-T2 were ineffective. KI did not alter the distribution of the uridine derivatives, UMP, UDP and UTP, as determined by the distribution of [3H]uridine in these compounds by paper chromatography, suggesting that the action of KI does not take place at the step of uridine phosphorylation. Like its effect on TSH, KI also impairs the stimulatory effect of exogenous cAMP and cGMP on RNA labelling, suggesting that its action is exerted beyond the step of cyclic nucleotide formation. Iodine and iodocompounds may exert their inhibitory action on RNA labelling at the step of nucleotide polymerization.", "contents": "Action of KI and several iodocompounds on [3H]uridine incorporation into thyroid RNA. The present studies were performed in order to further clarify the action of iodine and iodocompounds on the incorporation of labelled uridine into thyroid RNA. KI decreased RNA labelling but did not alter total [3H]uridine uptake or [3H]inulin distribution space. KI also inhibited the increase in RNA labelling produced by 8 mM glucose. T4 was more potent on a molar basis than KI in impairing uridine incorporation. TETRAC, TRIAC and isopropyl-T3 also decreased RNA labelling, while T2 and isopropyl-T2 were ineffective. KI did not alter the distribution of the uridine derivatives, UMP, UDP and UTP, as determined by the distribution of [3H]uridine in these compounds by paper chromatography, suggesting that the action of KI does not take place at the step of uridine phosphorylation. Like its effect on TSH, KI also impairs the stimulatory effect of exogenous cAMP and cGMP on RNA labelling, suggesting that its action is exerted beyond the step of cyclic nucleotide formation. Iodine and iodocompounds may exert their inhibitory action on RNA labelling at the step of nucleotide polymerization."}
{"id": "PMID:211783", "title": "Some histochemical observations on the myocardial metabolism in experimental conditions. Part I.", "content": "In the paper the author is concerned with the histochemical estimation of the metabolic adaptation of the heart muscle of albino rats during an early experimental alloxan diabetes. It has been found that the state of experimentally produced insulin deficiency directly influences metabolism of the heart muscle and the changes observed in the histochemical reactions prove this. An increase in the intensity of histochemical reactions concerns the PAS-positive reaction and the reactions to the NADH and NADPH tetrazole reductase activities. Alkaline phosphatase shows a decrease in the enzymatic activity, whose nature is transitional and reversible with regard to cytochrome oxidase and ATP-ase. The histochemical picture of metabolic changes depends on the duration time of experimental diabetes.", "contents": "Some histochemical observations on the myocardial metabolism in experimental conditions. Part I. In the paper the author is concerned with the histochemical estimation of the metabolic adaptation of the heart muscle of albino rats during an early experimental alloxan diabetes. It has been found that the state of experimentally produced insulin deficiency directly influences metabolism of the heart muscle and the changes observed in the histochemical reactions prove this. An increase in the intensity of histochemical reactions concerns the PAS-positive reaction and the reactions to the NADH and NADPH tetrazole reductase activities. Alkaline phosphatase shows a decrease in the enzymatic activity, whose nature is transitional and reversible with regard to cytochrome oxidase and ATP-ase. The histochemical picture of metabolic changes depends on the duration time of experimental diabetes."}
{"id": "PMID:211784", "title": "[Quantitative investigations of the zonal distribution of SDH, G6Pase and malic enzyme activity in liver parenchyma (author's transl)].", "content": "In native cryostat tissue sections of adult female albino rat liver the activities of succinate dehydrogenase (E. C. 1.3.99.1), glucose-6-phosphatase (E. C. 3.1.3.9) and malic enzyme (E. C. 1.1.1.40) were histochemically demonstrated and planimetrically determined. The areas of the enzymes with a maximum activity in the periportal regions, namely SDH and G-6-Pase, were respectively 34% and 41% of the whole parenchyma. Malic enzyme showed a maximum activity in the perivenous region, which consisted of about 53% of the total parenchyma. The zonal distribution of enzyme activities is related only to the terminal vessels; in the vicinity of the preterminal vessels an irregular distribution pattern was found. The results further support the assumption of the bifunctionality of liver parenchyma.", "contents": "[Quantitative investigations of the zonal distribution of SDH, G6Pase and malic enzyme activity in liver parenchyma (author's transl)]. In native cryostat tissue sections of adult female albino rat liver the activities of succinate dehydrogenase (E. C. 1.3.99.1), glucose-6-phosphatase (E. C. 3.1.3.9) and malic enzyme (E. C. 1.1.1.40) were histochemically demonstrated and planimetrically determined. The areas of the enzymes with a maximum activity in the periportal regions, namely SDH and G-6-Pase, were respectively 34% and 41% of the whole parenchyma. Malic enzyme showed a maximum activity in the perivenous region, which consisted of about 53% of the total parenchyma. The zonal distribution of enzyme activities is related only to the terminal vessels; in the vicinity of the preterminal vessels an irregular distribution pattern was found. The results further support the assumption of the bifunctionality of liver parenchyma."}
{"id": "PMID:211785", "title": "[Accumulation of phosphate ions in biological materials, phosphate ion diffusion and electron microscopical investigations of phosphohydrolases (author's transl)].", "content": "Isolated unfixed nuclei of mouse liver accumulate different amounts of phosphate ions dependent on pH, temperature and concentration of phosphate ions. At 37 degrees C and pH = 7.2, 8.5 X 10(9) binding places and a stability constant of 2.0 +/- 0,5 . 10(4) l/mol were calculated, the data at 30 degrees C and pH = 6.5 are 4 X 10(9) Nucleus-1 and 6 X 10(3) l/mol. Nuclei fixed by formaldehyde-ethanol or glutaraldehyde do not accumulated phosphate ions. Under conditions of nearly undisturbed diffusion phosphate ions taken up by the nuclei and precipitated by the help of lead ions are detected electron microscopically in the nuclear envelope, preferently in intracisternal space. Nucleoprotein structures do not show enrichments of crystals. These structures are also not stained after precipitation of phosphate ions under conditions of diminuation of diffusion. A possible mode of phosphate binding in cell nuclei and the influence of adsorbed phosphate ions on localization of enzymatic activities are discussed.", "contents": "[Accumulation of phosphate ions in biological materials, phosphate ion diffusion and electron microscopical investigations of phosphohydrolases (author's transl)]. Isolated unfixed nuclei of mouse liver accumulate different amounts of phosphate ions dependent on pH, temperature and concentration of phosphate ions. At 37 degrees C and pH = 7.2, 8.5 X 10(9) binding places and a stability constant of 2.0 +/- 0,5 . 10(4) l/mol were calculated, the data at 30 degrees C and pH = 6.5 are 4 X 10(9) Nucleus-1 and 6 X 10(3) l/mol. Nuclei fixed by formaldehyde-ethanol or glutaraldehyde do not accumulated phosphate ions. Under conditions of nearly undisturbed diffusion phosphate ions taken up by the nuclei and precipitated by the help of lead ions are detected electron microscopically in the nuclear envelope, preferently in intracisternal space. Nucleoprotein structures do not show enrichments of crystals. These structures are also not stained after precipitation of phosphate ions under conditions of diminuation of diffusion. A possible mode of phosphate binding in cell nuclei and the influence of adsorbed phosphate ions on localization of enzymatic activities are discussed."}
{"id": "PMID:211786", "title": "Sensory denervation of the plantar lumbrical muscle spindles in pyridoxine neuropathy.", "content": "Male albino rats treated with excessive amounts of pyridoxine developed an impairment of neuromuscular function. The equatorial region of the plantar lumbrical intrafusal muscle fibres was studied in the electron microscope and the calibre of the nerve fibres was determined in semi-thin sections of the posterior tibial nerves. Degeneration of the primary sensory endings coincided with the onset of ataxia, and in more advanced stages of the neuropathy as well as after a 2-month treatment-free period the equatorial region was denervated. There was a corresponding decrease in the number of large nerve fibres. It is considered essential that primary sensory endings of lumbrical muscle spindles should be included in studies of distally accentuated sensory neuropathies.", "contents": "Sensory denervation of the plantar lumbrical muscle spindles in pyridoxine neuropathy. Male albino rats treated with excessive amounts of pyridoxine developed an impairment of neuromuscular function. The equatorial region of the plantar lumbrical intrafusal muscle fibres was studied in the electron microscope and the calibre of the nerve fibres was determined in semi-thin sections of the posterior tibial nerves. Degeneration of the primary sensory endings coincided with the onset of ataxia, and in more advanced stages of the neuropathy as well as after a 2-month treatment-free period the equatorial region was denervated. There was a corresponding decrease in the number of large nerve fibres. It is considered essential that primary sensory endings of lumbrical muscle spindles should be included in studies of distally accentuated sensory neuropathies."}
{"id": "PMID:211787", "title": "Ultrastructural localization of rabies virus antigens in infected trigeminal ganglion of hamsters.", "content": "The trigeminal ganglion of hamsters infected with CVS strain of rabies virus was investigated by electron microscopy with peroxidase-labeled antibody. Major localization of virus antigens were the following three types of structures; rabies virion, cytoplasmic inclusion, and ribosomal granules consisting of Nissl body. Rabies virions in neurons were mostly found within the cluster of such ribosome-rich regions suggesting a close relationship between the two in the synthesis of virus antigen. The cytoplasmic inclusion appeared to be derived from ribosomal or allied particles with virus-specific antigens. The significance of results obtained is briefly discussed.", "contents": "Ultrastructural localization of rabies virus antigens in infected trigeminal ganglion of hamsters. The trigeminal ganglion of hamsters infected with CVS strain of rabies virus was investigated by electron microscopy with peroxidase-labeled antibody. Major localization of virus antigens were the following three types of structures; rabies virion, cytoplasmic inclusion, and ribosomal granules consisting of Nissl body. Rabies virions in neurons were mostly found within the cluster of such ribosome-rich regions suggesting a close relationship between the two in the synthesis of virus antigen. The cytoplasmic inclusion appeared to be derived from ribosomal or allied particles with virus-specific antigens. The significance of results obtained is briefly discussed."}
{"id": "PMID:211788", "title": "Effects of terbutaline on the pressure volume relationship in fetal rabbit lung.", "content": "The pressure-volume relationship in preterm rabbit lung was studied at 28 days of gestation. Injection of 0.1 mg terbutaline, a selective beta2-receptor stimulating drug, significantly increased the volume of air at equivalent low transpulmonary pressures, compared to a saline treated group and an untreated group. These findings indicate an increased pulmonary distensibility of the fetal rabbit lung after terbutaline administration. The mechanism of action is discussed and surfactant mediated effects are suggested to be the probable explanation.", "contents": "Effects of terbutaline on the pressure volume relationship in fetal rabbit lung. The pressure-volume relationship in preterm rabbit lung was studied at 28 days of gestation. Injection of 0.1 mg terbutaline, a selective beta2-receptor stimulating drug, significantly increased the volume of air at equivalent low transpulmonary pressures, compared to a saline treated group and an untreated group. These findings indicate an increased pulmonary distensibility of the fetal rabbit lung after terbutaline administration. The mechanism of action is discussed and surfactant mediated effects are suggested to be the probable explanation."}
{"id": "PMID:211790", "title": "Ultrasonography and computer tomography in orbital diagnosis. With special reference to dysthyroid ophthalmopathy.", "content": "A report is given on a series of 162 patients referred for ultrasound examination (US, A-mode) due to orbital disease. 101 also had computerized tomography (CT, Emi scanner Mark I, 160 X 160 matrix, 8 mm sections), the results of which were emphasized in a recent publication (Gyldensted et al. 1977). The present approach is primarily clinical. With histopathological confirmation in only 40% of the cases, it is difficult to give exact values for diagnostic accuracy, but it appeared to be above 90% for CT, and close to this value for US (depending on, of course, how specified the diagnostic predictions were). Dysthyroid ophthalmopathy (DO, orbital Graves' disease, endocrine exophthalmos) was the most frequent cause of unilateral protrusion (24 cases). In some such cases \"tumour-positive\" CT scans represent a diagnostic pitfall, unless the examiner is familiar with the clinical features of DO. In the present series, for example, one of the DO cases had transcranial exploration of the orbit. The two--indeed valuable--non-invasive methods (CT and US) should be assessed in combination, and also combined with the classic clinical evaluation of the patient.", "contents": "Ultrasonography and computer tomography in orbital diagnosis. With special reference to dysthyroid ophthalmopathy. A report is given on a series of 162 patients referred for ultrasound examination (US, A-mode) due to orbital disease. 101 also had computerized tomography (CT, Emi scanner Mark I, 160 X 160 matrix, 8 mm sections), the results of which were emphasized in a recent publication (Gyldensted et al. 1977). The present approach is primarily clinical. With histopathological confirmation in only 40% of the cases, it is difficult to give exact values for diagnostic accuracy, but it appeared to be above 90% for CT, and close to this value for US (depending on, of course, how specified the diagnostic predictions were). Dysthyroid ophthalmopathy (DO, orbital Graves' disease, endocrine exophthalmos) was the most frequent cause of unilateral protrusion (24 cases). In some such cases \"tumour-positive\" CT scans represent a diagnostic pitfall, unless the examiner is familiar with the clinical features of DO. In the present series, for example, one of the DO cases had transcranial exploration of the orbit. The two--indeed valuable--non-invasive methods (CT and US) should be assessed in combination, and also combined with the classic clinical evaluation of the patient."}
{"id": "PMID:211791", "title": "Pigment changes of the retina in chronic progressive external ophthalmoplegia (CPEO).", "content": "A study was made of the retinal functions in 4 patients with chronic progressive external ophthalmoplegia, general myopathy, EEG anomalies and pigment changes of the fundus oculi (ophthalmoplegia-plus). Three of them exhibited typical, granular pigmentations in a linear or reticular arrangement at the periphery. All four showed slight to moderate pigment epithelial defects in the maculae, mostly only discernible with fluorescence angiography. In all 4 cases, a slight decrease of the visual acuity, a mildly abnormal ERG, mild concentric restriction of the field of vision and, in two cases, an abnormal dark-adaptation curve led to the conclusion of a mild diffuse, widely disseminated receptor affection of the retina (both rods and cones). The EOG appeared normal in 3, and at the lower limit of normal in 1 case. On the basis of a detailed study of the literature we can conclude that the retinal lesions in chronic progressive external ophthalmoplegia may vary from benign pigmentations without functional impairment to genuine 'retinitis pigmentosa' with all gradations of rod-cone or cone-rod dystrophy. Emphasis is laid on the possibility of a correlation between the mitochondrial abnormalities encountered in ocular myopathy and ophthalmoplegia-plus on the one hand, and the retinal abnormalities on the other, with special reference to a possible disorder of the utilization of pyruvate in the citric-acid cycle and a loose coupling of the oxidative phosphorylation.", "contents": "Pigment changes of the retina in chronic progressive external ophthalmoplegia (CPEO). A study was made of the retinal functions in 4 patients with chronic progressive external ophthalmoplegia, general myopathy, EEG anomalies and pigment changes of the fundus oculi (ophthalmoplegia-plus). Three of them exhibited typical, granular pigmentations in a linear or reticular arrangement at the periphery. All four showed slight to moderate pigment epithelial defects in the maculae, mostly only discernible with fluorescence angiography. In all 4 cases, a slight decrease of the visual acuity, a mildly abnormal ERG, mild concentric restriction of the field of vision and, in two cases, an abnormal dark-adaptation curve led to the conclusion of a mild diffuse, widely disseminated receptor affection of the retina (both rods and cones). The EOG appeared normal in 3, and at the lower limit of normal in 1 case. On the basis of a detailed study of the literature we can conclude that the retinal lesions in chronic progressive external ophthalmoplegia may vary from benign pigmentations without functional impairment to genuine 'retinitis pigmentosa' with all gradations of rod-cone or cone-rod dystrophy. Emphasis is laid on the possibility of a correlation between the mitochondrial abnormalities encountered in ocular myopathy and ophthalmoplegia-plus on the one hand, and the retinal abnormalities on the other, with special reference to a possible disorder of the utilization of pyruvate in the citric-acid cycle and a loose coupling of the oxidative phosphorylation."}
{"id": "PMID:211792", "title": "The process of wound healing of the avascular outer layers of the retina. Light- and electron microscopic studies on laser lesions of monkey eyes.", "content": "The process of wound healing of the avascular outer layers of the retina is studied on a series of Laser lesions of the monkey, Cercopithecus aethiops. The extent of the retinal lesions is limited to the pigment epithelium and photoreceptor cells, whereas Bruch's membrane and the vascular inner layers of the retina intact. The retinal lesions are not seen to be invaded by cells from the choroid, nor from the retinal vessels. During the first three days after irradiation the pigment epithelial cells in a zone, about 75 micrometer wide, around the lesions appear to be changed into bi- or multinucleate cells with the additional nuclei situated in apical cytoplasmic protrusions which extend towards and into the lesions. During the second and third days after irradiation the lesions are invaded by two kinds of cells which both appear to arise through the off-budding of the nucleus-containing apical protrusions of the pigment epithelial cells around the lesions: (a) phagocytic cells which disintegrate the damaged tissue and, as this process is completed 4--9 days after irradiation show evidence of melanogenesis; and (b) regenerated pigment epithelium which form a single layer of cells along Bruch's membrane, but show no evidence of phagocytosis or intracellular disintegration of the damaged tissue. Within the lesions both these kinds of cells show mitotic figures the third day after irradiation.", "contents": "The process of wound healing of the avascular outer layers of the retina. Light- and electron microscopic studies on laser lesions of monkey eyes. The process of wound healing of the avascular outer layers of the retina is studied on a series of Laser lesions of the monkey, Cercopithecus aethiops. The extent of the retinal lesions is limited to the pigment epithelium and photoreceptor cells, whereas Bruch's membrane and the vascular inner layers of the retina intact. The retinal lesions are not seen to be invaded by cells from the choroid, nor from the retinal vessels. During the first three days after irradiation the pigment epithelial cells in a zone, about 75 micrometer wide, around the lesions appear to be changed into bi- or multinucleate cells with the additional nuclei situated in apical cytoplasmic protrusions which extend towards and into the lesions. During the second and third days after irradiation the lesions are invaded by two kinds of cells which both appear to arise through the off-budding of the nucleus-containing apical protrusions of the pigment epithelial cells around the lesions: (a) phagocytic cells which disintegrate the damaged tissue and, as this process is completed 4--9 days after irradiation show evidence of melanogenesis; and (b) regenerated pigment epithelium which form a single layer of cells along Bruch's membrane, but show no evidence of phagocytosis or intracellular disintegration of the damaged tissue. Within the lesions both these kinds of cells show mitotic figures the third day after irradiation."}
{"id": "PMID:211793", "title": "The isozyme pattern of cyclic AMP-dependent protein kinase and the distribution of a cervicovaginal antigen in experimental carcinoma of the cervix uteri of mice.", "content": "Tissue-sections from 12 methylcholanthrene-induced carcinomas of the cervix uteri of mice were tested for the presence of an antigen normally confined to the cervicovaginal epithelium. The antigen was detected in 10 of the 12 tumours investigated with indirect immunofluorescence, and in all 7 tumours studied with the more sensitive method of mixed hemagglutination. The concentration of the antigen was generally higher in the well-differentiated areas of the tumours, but it was also found associated with solitary tumour cells, apparently invading the stroma. The presence of CVA in the tumours suggests an origin of the tumour cells from the cervicovaginal epithelium. The cyclic AMP dependent protein kinase (EC 2. 7. 1. 37) in the tumour cytosols was studied by chromatography on agarose and DEAE-cellulose. The enzyme showed the same properties as that from normal vaginal epithelium. The tumour cells thus contain an apparently normal complement of this enzyme, which is believed to be responsible for most of the intracellular actions of cyclic AMP.", "contents": "The isozyme pattern of cyclic AMP-dependent protein kinase and the distribution of a cervicovaginal antigen in experimental carcinoma of the cervix uteri of mice. Tissue-sections from 12 methylcholanthrene-induced carcinomas of the cervix uteri of mice were tested for the presence of an antigen normally confined to the cervicovaginal epithelium. The antigen was detected in 10 of the 12 tumours investigated with indirect immunofluorescence, and in all 7 tumours studied with the more sensitive method of mixed hemagglutination. The concentration of the antigen was generally higher in the well-differentiated areas of the tumours, but it was also found associated with solitary tumour cells, apparently invading the stroma. The presence of CVA in the tumours suggests an origin of the tumour cells from the cervicovaginal epithelium. The cyclic AMP dependent protein kinase (EC 2. 7. 1. 37) in the tumour cytosols was studied by chromatography on agarose and DEAE-cellulose. The enzyme showed the same properties as that from normal vaginal epithelium. The tumour cells thus contain an apparently normal complement of this enzyme, which is believed to be responsible for most of the intracellular actions of cyclic AMP."}
{"id": "PMID:211794", "title": "Human malignant lymphomas in vitro. Characterization of biopsy cells and establishment of permanent cell lines.", "content": "A series of 55 biopsies from different types of malignant lymphomas were characterized in short-term culture experiments and during prolonged growth in vitro. The majority of the lymphocytic lymphomas and half of the histiocytic lymphomas expressed surface immunoglobulin, either in monoclonal or polyclonal form, indicating B-lymphocyte derivation. No lysozyme production was noted in either type of lymphoma, giving further support to the notion that histiocytic lymphomas are not truly histiocytic. Production of beta2-microglobulin was higher in histiocytic than in lymphocytic lymphoma and Hodgkin's disease but did not significantly differ from the production observed in non-neoplastic lymph node disorders. Incorporation of 3H-thymidine varied greatly within each category of lymphoma; the highest mean labelling index was noted in histiocytic lymphoma, possibly reflecting the generally more malignant course in such cases. Epstein-Barr virus-associated nuclear antigen was observed in one case of Hodgkin's disease. Attempts to establish permanent tumor cell lines were successful only from two explants of lymphocytic lymphoma and one pleural effusion from histiocytic lymphoma. The two cell lines derived from lymphocytic lymphomas both exhibited B-lymphocyte characteristics. The histiocytic lymphoma line lacked lymphocyte markers, produced lysozyme and was found to be rich in cytoplasmic esterases. These features are consistent with a \"true\" histiocytic derivation of this line. Lymphoblastoid cell lines representing non-neoplastic EBV-carrying lymphocytes contaminating the biopsies were derived from 19 biopsies, with the highest frequency noted in cultures of biopsies from Hodgkin's disease. The tumor lines were all EBV-genome negative.", "contents": "Human malignant lymphomas in vitro. Characterization of biopsy cells and establishment of permanent cell lines. A series of 55 biopsies from different types of malignant lymphomas were characterized in short-term culture experiments and during prolonged growth in vitro. The majority of the lymphocytic lymphomas and half of the histiocytic lymphomas expressed surface immunoglobulin, either in monoclonal or polyclonal form, indicating B-lymphocyte derivation. No lysozyme production was noted in either type of lymphoma, giving further support to the notion that histiocytic lymphomas are not truly histiocytic. Production of beta2-microglobulin was higher in histiocytic than in lymphocytic lymphoma and Hodgkin's disease but did not significantly differ from the production observed in non-neoplastic lymph node disorders. Incorporation of 3H-thymidine varied greatly within each category of lymphoma; the highest mean labelling index was noted in histiocytic lymphoma, possibly reflecting the generally more malignant course in such cases. Epstein-Barr virus-associated nuclear antigen was observed in one case of Hodgkin's disease. Attempts to establish permanent tumor cell lines were successful only from two explants of lymphocytic lymphoma and one pleural effusion from histiocytic lymphoma. The two cell lines derived from lymphocytic lymphomas both exhibited B-lymphocyte characteristics. The histiocytic lymphoma line lacked lymphocyte markers, produced lysozyme and was found to be rich in cytoplasmic esterases. These features are consistent with a \"true\" histiocytic derivation of this line. Lymphoblastoid cell lines representing non-neoplastic EBV-carrying lymphocytes contaminating the biopsies were derived from 19 biopsies, with the highest frequency noted in cultures of biopsies from Hodgkin's disease. The tumor lines were all EBV-genome negative."}
{"id": "PMID:211795", "title": "The first tick-borne encephalitis virus isolates from Norway.", "content": "Five virus strains with close serological relationship to the tick-borne encephalitis (TBE) complex have been isolated from Ixodes ricinus ticks. The ticks were collected in early June 1976 at three different locations in Sogn & Fjordane County, Norway. One of the virus-yielding pools was composed of ticks collected between the cabins on a tourist camping ground.", "contents": "The first tick-borne encephalitis virus isolates from Norway. Five virus strains with close serological relationship to the tick-borne encephalitis (TBE) complex have been isolated from Ixodes ricinus ticks. The ticks were collected in early June 1976 at three different locations in Sogn & Fjordane County, Norway. One of the virus-yielding pools was composed of ticks collected between the cabins on a tourist camping ground."}
{"id": "PMID:211796", "title": "Metabolic adaptation to hypoxia. Redox state of the cellular free NAD pools, phosphorylation state of the adenylate system and the (Na+-K+)-stimulated ATP-ase in rat liver.", "content": "The effect of hypoxia (30 min 10% or 8% O2) on the phosphorylation state and redox state of the cytosol and mitochondria of rat liver were studied. Measurements were made both from normal animals and animals which had been exposed to the reduced partial pressure of oxygen (50.5 kPa or 40.8 kPa of air) for one or seven days. Cytostolic free NAD was reduced in the liver both in acute hypoxia and in hypoxia after one or seven days, i.e. the lactate/pyruvate and sn-glycerol-3-phosphate/dioxyacetonephosphate ratios increased markedly. A marked reduction in the mitochondrial free NAD pool occurred only in acute hypoxia and only a slight reduction was observed in animals kept at 40.8 kPa for one or seven days, as evaluated from the hepatic hydroxybutyrate/acetoacetate ratio. Liver ATP concentration decreased rapidly in acute hypoxia without any significant recovery during one or seven days at 40.8 kPa. The hepatic ATP/ADP X Pi ratio decreased significantly, with a simultaneous decrease in the total adenine nucleotide concentration. A tendency was observed for the ATP/ADP X Pi ratio to return to normal after seven days, i.e. the values in acute hypoxia were significantly smaller than those noted in hypoxia after seven days, demonstrating an adaptation of the energy metabolism during prolonged hypoxia. Hepatic (Na+-K+)-stimulated ATP-ase activity was not affected by hypoxia.", "contents": "Metabolic adaptation to hypoxia. Redox state of the cellular free NAD pools, phosphorylation state of the adenylate system and the (Na+-K+)-stimulated ATP-ase in rat liver. The effect of hypoxia (30 min 10% or 8% O2) on the phosphorylation state and redox state of the cytosol and mitochondria of rat liver were studied. Measurements were made both from normal animals and animals which had been exposed to the reduced partial pressure of oxygen (50.5 kPa or 40.8 kPa of air) for one or seven days. Cytostolic free NAD was reduced in the liver both in acute hypoxia and in hypoxia after one or seven days, i.e. the lactate/pyruvate and sn-glycerol-3-phosphate/dioxyacetonephosphate ratios increased markedly. A marked reduction in the mitochondrial free NAD pool occurred only in acute hypoxia and only a slight reduction was observed in animals kept at 40.8 kPa for one or seven days, as evaluated from the hepatic hydroxybutyrate/acetoacetate ratio. Liver ATP concentration decreased rapidly in acute hypoxia without any significant recovery during one or seven days at 40.8 kPa. The hepatic ATP/ADP X Pi ratio decreased significantly, with a simultaneous decrease in the total adenine nucleotide concentration. A tendency was observed for the ATP/ADP X Pi ratio to return to normal after seven days, i.e. the values in acute hypoxia were significantly smaller than those noted in hypoxia after seven days, demonstrating an adaptation of the energy metabolism during prolonged hypoxia. Hepatic (Na+-K+)-stimulated ATP-ase activity was not affected by hypoxia."}
{"id": "PMID:211797", "title": "The effect of vigorous physical activity at work on serum lipids with a special reference to serum high-density lipoprotein cholesterol.", "content": "Serum lipid concentrations of lumberjacks whose occupational physical activity is most vigorous were compared with those of electricians. The lumberjacks had significantly higher serum HDL-cholesterol and significantly lower triglyceride and free fatty acid concentrations but there were no significant differences in total cholesterol levels. The favourable effect of vigorous physical activity at work on lipid metabolism is, however, epidemiologically not seen, obviously due to negative risk factors in lumberjacks' life.", "contents": "The effect of vigorous physical activity at work on serum lipids with a special reference to serum high-density lipoprotein cholesterol. Serum lipid concentrations of lumberjacks whose occupational physical activity is most vigorous were compared with those of electricians. The lumberjacks had significantly higher serum HDL-cholesterol and significantly lower triglyceride and free fatty acid concentrations but there were no significant differences in total cholesterol levels. The favourable effect of vigorous physical activity at work on lipid metabolism is, however, epidemiologically not seen, obviously due to negative risk factors in lumberjacks' life."}
{"id": "PMID:211798", "title": "The relationship between cortical recruiting responses and ponto-geniculo-occipital waves during paradoxical sleep in the cat.", "content": "In an earlier study it was found that during paradoxical sleep (PS) thalamo-cortical recruiting responses (RRs) and rapid eye movements usually did not appear simultaneously. As shown elsewhere, ponto-geniculo-occipital (PGO) wave activity and rapid eye movements are during PS closely related to each other in time. Similarly, in the present study it was observed that during paradoxical sleep in cats in which the center median nucleus of the thalamus was being stimulated at a rate of 7--9 Hz PGO waves in the geniculate nuclei did not in the rule occur in the presence of RRs recorded from the motor cortex. This effect was most pronounced with respect to series of PGO waves which usually occur at a rate of 4--7 Hz. On the basis of these experiments it was concluded that PGO waves and RRs are reciprocal events and mutually exclusive. Considering to the well-known fact that RRs represent synchronization, this negative correlation between RRs and PGO waves indicates that the desynchronizing tendency typical to paradoxical sleep is most pronounced during the occurrence of PGO waves.", "contents": "The relationship between cortical recruiting responses and ponto-geniculo-occipital waves during paradoxical sleep in the cat. In an earlier study it was found that during paradoxical sleep (PS) thalamo-cortical recruiting responses (RRs) and rapid eye movements usually did not appear simultaneously. As shown elsewhere, ponto-geniculo-occipital (PGO) wave activity and rapid eye movements are during PS closely related to each other in time. Similarly, in the present study it was observed that during paradoxical sleep in cats in which the center median nucleus of the thalamus was being stimulated at a rate of 7--9 Hz PGO waves in the geniculate nuclei did not in the rule occur in the presence of RRs recorded from the motor cortex. This effect was most pronounced with respect to series of PGO waves which usually occur at a rate of 4--7 Hz. On the basis of these experiments it was concluded that PGO waves and RRs are reciprocal events and mutually exclusive. Considering to the well-known fact that RRs represent synchronization, this negative correlation between RRs and PGO waves indicates that the desynchronizing tendency typical to paradoxical sleep is most pronounced during the occurrence of PGO waves."}
{"id": "PMID:211799", "title": "Oxidative and lysosomal capacity in skeletal muscle of mice after endurance training of different intensities.", "content": "The activity of certain enzymes of energy metabolism (cytochrome c oxidase, citrate synthase, malate dehydrogenase, and lactate dehydrogenase) and of lysosomes (beta-glucuronidase, beta-N-acetylglucosamindase, arylsuphatase, ribonuclease, deoxyribonuclease, acid phosphatase, and cathepsin D) was assayed from m. rectus femoris of mice trained 5 days per week, 1 hr per day for 4 weeks according to 4 different programmes: I. running speed 20 m/min, horizontal track, II. 25 m/min, horizontal track, III. 20 m/min 8 degrees uphill inclination, and IV. 25 m/min 8 degrees uphill inclination. Oxidative capacity increased and anaerobic capacity decreased without distinction between the different traning programmes. Of acid hydrolases assayed the activities of beta-glucuronidase and cathepsin D were increased independently of training intensity. Simultaneous histochemical observations on beta-glucuronidase and arylsulphatase activities in the contralateral m. rectus femoris showed more intense staining in red as compared to white muscle fibres. It is suggested that training affected the red fibres and that the applied level of loading was probably too low to cause major involvement of white fibres.", "contents": "Oxidative and lysosomal capacity in skeletal muscle of mice after endurance training of different intensities. The activity of certain enzymes of energy metabolism (cytochrome c oxidase, citrate synthase, malate dehydrogenase, and lactate dehydrogenase) and of lysosomes (beta-glucuronidase, beta-N-acetylglucosamindase, arylsuphatase, ribonuclease, deoxyribonuclease, acid phosphatase, and cathepsin D) was assayed from m. rectus femoris of mice trained 5 days per week, 1 hr per day for 4 weeks according to 4 different programmes: I. running speed 20 m/min, horizontal track, II. 25 m/min, horizontal track, III. 20 m/min 8 degrees uphill inclination, and IV. 25 m/min 8 degrees uphill inclination. Oxidative capacity increased and anaerobic capacity decreased without distinction between the different traning programmes. Of acid hydrolases assayed the activities of beta-glucuronidase and cathepsin D were increased independently of training intensity. Simultaneous histochemical observations on beta-glucuronidase and arylsulphatase activities in the contralateral m. rectus femoris showed more intense staining in red as compared to white muscle fibres. It is suggested that training affected the red fibres and that the applied level of loading was probably too low to cause major involvement of white fibres."}
{"id": "PMID:211801", "title": "Cell population kinetics and dose-time relationships for post-irradiation injury of the brachial plexus in man.", "content": "Collected data on radiation-induced lesions of the brachial plexus were analyzed on the assumption that this reaction arises from depletion of some unidentified cell population in the irradiated tissues. A multi-probit search program was used to derive best-fitting cell kinetic parameters in a composite multi-target model for cellular radiation lethality and repopulation. From these parameters, a comprehensive iso-effect table, for a wide range of treatment schedules including daily treatment as well as fractionation at shorter and longer intervals, was constructed. The table provides a useful set of tolerance dosage limits for late effects in irradiated peripheral nerve.", "contents": "Cell population kinetics and dose-time relationships for post-irradiation injury of the brachial plexus in man. Collected data on radiation-induced lesions of the brachial plexus were analyzed on the assumption that this reaction arises from depletion of some unidentified cell population in the irradiated tissues. A multi-probit search program was used to derive best-fitting cell kinetic parameters in a composite multi-target model for cellular radiation lethality and repopulation. From these parameters, a comprehensive iso-effect table, for a wide range of treatment schedules including daily treatment as well as fractionation at shorter and longer intervals, was constructed. The table provides a useful set of tolerance dosage limits for late effects in irradiated peripheral nerve."}
{"id": "PMID:211803", "title": "Familial lecithin: cholesterol acyltransferase deficiency complicated with unconjugated hyperbilirubinemia and peripheral neuropathy. The first reported cases in the Far East.", "content": "Three Japanese patients with lecithin: cholesterol acyltransferase (LCAT) deficiency, the offspring of a consanguineous marriage, are described. In addition to the characteristic clinical and laboratory findings of the disease, our patients had hitherto unreported manifestations, namely unconjugated hyperbilirubinemia, peripheral neuropathy and marked hypocholesterolemia. Although the mechanism of the unconjugated hyperbilirubinemia is not clear, the role of impaired hepatic bilirubin uridine-diphosphate-glucuronyl transferase activity combined with another unknown factor(s) was postulated. Non-random assortment was observed between LCAT deficiency and haptoglobin types, as previously reported. The discovery of Japanese patients with LCAT deficiency indicates that the distribution of this hereditary metabolic disorder is not confined to the Western hemisphere.", "contents": "Familial lecithin: cholesterol acyltransferase deficiency complicated with unconjugated hyperbilirubinemia and peripheral neuropathy. The first reported cases in the Far East. Three Japanese patients with lecithin: cholesterol acyltransferase (LCAT) deficiency, the offspring of a consanguineous marriage, are described. In addition to the characteristic clinical and laboratory findings of the disease, our patients had hitherto unreported manifestations, namely unconjugated hyperbilirubinemia, peripheral neuropathy and marked hypocholesterolemia. Although the mechanism of the unconjugated hyperbilirubinemia is not clear, the role of impaired hepatic bilirubin uridine-diphosphate-glucuronyl transferase activity combined with another unknown factor(s) was postulated. Non-random assortment was observed between LCAT deficiency and haptoglobin types, as previously reported. The discovery of Japanese patients with LCAT deficiency indicates that the distribution of this hereditary metabolic disorder is not confined to the Western hemisphere."}
{"id": "PMID:211804", "title": "Small cell carcinoma of the lung: serum calcitonin and serum histaminase (diamine oxidase) at basal levels and stimulated by pentagastrin.", "content": "Investigations were performed to evaluate the incidence of increased serum calcitonin and histaminase in 79 patients with untreated small cell carcinoma of the lung (SSC). In addition, serum calcitonin was measured following pentagastrin stimulation in 19 of these patients. Serum calcitonin was elevated in 54 of 79 patients (68%), 20 patients (25%) having a level usually associated with the diagnosis of medullary carcinoma of the thyroid (MCT). The levels of histaminase, on the other hand, did not differ from the distribution in normals. In three of 19 patients undergoing the pentagastrin stimulation test, calcitonin was significantly increased. Thus, serum calcitonin is frequently elevated in patients with SCC and a positive pentagastrin test is not pathognomonic of MCT.", "contents": "Small cell carcinoma of the lung: serum calcitonin and serum histaminase (diamine oxidase) at basal levels and stimulated by pentagastrin. Investigations were performed to evaluate the incidence of increased serum calcitonin and histaminase in 79 patients with untreated small cell carcinoma of the lung (SSC). In addition, serum calcitonin was measured following pentagastrin stimulation in 19 of these patients. Serum calcitonin was elevated in 54 of 79 patients (68%), 20 patients (25%) having a level usually associated with the diagnosis of medullary carcinoma of the thyroid (MCT). The levels of histaminase, on the other hand, did not differ from the distribution in normals. In three of 19 patients undergoing the pentagastrin stimulation test, calcitonin was significantly increased. Thus, serum calcitonin is frequently elevated in patients with SCC and a positive pentagastrin test is not pathognomonic of MCT."}
{"id": "PMID:211806", "title": "Mathematics of the inverse solid-phase radioimmunoassay.", "content": "Use of a simplified, idealized model allows a mathematical treatment of the inverse solid phase radioimmunoassay. Equations are presented for calculation of the following values: bound/free antibody ratio (R) in the state of equilibrium; the equilibrium constant (K), the concentrations of the directly non-measurable values (Abf; AbfAg: Abs and Ag) as well as the concentration of the antibody tested [Abf]0. The model has the same parameters as the test system, thus the equations may be used in planning of the test in the laboratory.", "contents": "Mathematics of the inverse solid-phase radioimmunoassay. Use of a simplified, idealized model allows a mathematical treatment of the inverse solid phase radioimmunoassay. Equations are presented for calculation of the following values: bound/free antibody ratio (R) in the state of equilibrium; the equilibrium constant (K), the concentrations of the directly non-measurable values (Abf; AbfAg: Abs and Ag) as well as the concentration of the antibody tested [Abf]0. The model has the same parameters as the test system, thus the equations may be used in planning of the test in the laboratory."}
{"id": "PMID:211807", "title": "Antibodies to rubellavirus, herpes simplex virus and Toxoplasma gondii in serial serum samples of pregnant and non-pregnant women.", "content": "By testing serial serum samples of 213 pregnant women for rubellavirus, of 196 for herpes simplex virus and of 134 for Toxoplasma gondii, it was found that during pregnancy there was a fall in the humoral antibody level. Presence and titre of antibodies were lower in sera of pregnant than of non-pregnant women. Alteration of the humoral antibody level during pregnancy may influence serological studies aimed at clarifying the role of infections in fetal malformations. Serial serum samples (4 samples from each pregnant woman involved) should be tested for obtaining reliable data regarding the frequency of infections during pregnancy.", "contents": "Antibodies to rubellavirus, herpes simplex virus and Toxoplasma gondii in serial serum samples of pregnant and non-pregnant women. By testing serial serum samples of 213 pregnant women for rubellavirus, of 196 for herpes simplex virus and of 134 for Toxoplasma gondii, it was found that during pregnancy there was a fall in the humoral antibody level. Presence and titre of antibodies were lower in sera of pregnant than of non-pregnant women. Alteration of the humoral antibody level during pregnancy may influence serological studies aimed at clarifying the role of infections in fetal malformations. Serial serum samples (4 samples from each pregnant woman involved) should be tested for obtaining reliable data regarding the frequency of infections during pregnancy."}
{"id": "PMID:211809", "title": "Post-operative stereotactic Curie-therapy using the iridium-192 GammaMed contact irradiation apparatus combined with radio-sensitizers in treating multiform glioblastomas.", "content": "Experimental investigations on the dimethyl-amino-stilbous carcino-sarcoma of the rat have led to a modified interstitial post-operative Curie-therapy of gliomas in the brain hemispheres following treatment with radio sensitizers. After treatment with the thymine-analogous radio-sensitizers 5-brom-2-desoxyuridine (BUDR) and 5-brom-2-desoxycytidine (BCDR) and desoxyguanosine as well as the anti-metabolites 5-fluor-uracile (FU) and methotrexate (Mtx), there is greater incorporation of the thymine analogues in the DNS of the tumour cells. More than any other combination, BUDR and Mtx effectively sensibilizes the tumour cells. Syncavit and actinomycine-D are also effective. After radio-sensitizing the post-iridium-192 contact irradiation apparatus on 133 patients with gliomas. This treatment lengthened postoperative survival times.", "contents": "Post-operative stereotactic Curie-therapy using the iridium-192 GammaMed contact irradiation apparatus combined with radio-sensitizers in treating multiform glioblastomas. Experimental investigations on the dimethyl-amino-stilbous carcino-sarcoma of the rat have led to a modified interstitial post-operative Curie-therapy of gliomas in the brain hemispheres following treatment with radio sensitizers. After treatment with the thymine-analogous radio-sensitizers 5-brom-2-desoxyuridine (BUDR) and 5-brom-2-desoxycytidine (BCDR) and desoxyguanosine as well as the anti-metabolites 5-fluor-uracile (FU) and methotrexate (Mtx), there is greater incorporation of the thymine analogues in the DNS of the tumour cells. More than any other combination, BUDR and Mtx effectively sensibilizes the tumour cells. Syncavit and actinomycine-D are also effective. After radio-sensitizing the post-iridium-192 contact irradiation apparatus on 133 patients with gliomas. This treatment lengthened postoperative survival times."}
{"id": "PMID:211808", "title": "Glioblastoma multiforme: morphology and biology.", "content": "Glioblastoma multiforme, representing about 50% of all gliomas, encompasses a group of intrinsic tumours of the brain in later years (age peak around 50 years), the morphological hallmarks of which are an ensemble of variations in tumour cell and tissue structure featuring its biological malignancy. Glioblastoma, while sometimes appearing as a distinct \"primary\" tumour type, is usually accepted as an extreme manifestation of anaplasia and dedifferentiation of glia, mostly astrocytic. The astrocytic nature of most glioblastomas has been confirmed by ultrastructural studies and progressive differentiation of tumours maintained in organotypic tissue culture. Reproducible experimental models are particularly induced by oncogenic RNA (oncorna) viruses. The cell kinetic parameters are similar to those of other solid malignant tumours except for a comparatively low growth fraction of glioblastoma. The frequent occurrence of giant cells as well as of regressive changes with necrosis and vascular responses are indirect (secondary) indicators of malignancy which coincide with histochemical (enzymatic anisochronia) and biochemical data (lower level of glia specific S100 protein than in differentiated gliomas). Vascular proliferation, a characteristic feature of glioblastoma, may occasionally progress to sarcomatous transformation with development of gliosarcomas (mixed glial-mesenchymal tumours). While dissemination of glioblastoma through the cerebrospinal pathways is not uncommon, extraneural distant metastatic spread is rare, and usually observed after craniotomy. The results of modern neuro-oncology support the pathogenetic view that glioblastoma results from neoplastic transformation of glial elements with continuing dedifferentiation. This transformation can be experimentally induced by various factors including oncogenic DNA (oncorna) viruses by using a reverse transcriptase, while there is indirect evidence for an oncorna-virus information in human glioblastoma. The significance of immunological factors in the pathogenesis of brain tumours and in the course of neoplastic transformation of glia is not yet understood, but both morphological and immunological data are in favour of a cell mediated immunological reaction against tumour-specific antibodies. Since immunological factors and changes in cytokinetics are apparently active after the transformed tumour cells proliferate, all available therapeutic methods, including radiation, chemotherapy, and immunotherapy of glioblastoma only influence the final stages of neoplastic development with clinical manifestation of the tumour. In spite of modern combination and multimodality therapy schemes the prognosis of glioblastoma is still poor.", "contents": "Glioblastoma multiforme: morphology and biology. Glioblastoma multiforme, representing about 50% of all gliomas, encompasses a group of intrinsic tumours of the brain in later years (age peak around 50 years), the morphological hallmarks of which are an ensemble of variations in tumour cell and tissue structure featuring its biological malignancy. Glioblastoma, while sometimes appearing as a distinct \"primary\" tumour type, is usually accepted as an extreme manifestation of anaplasia and dedifferentiation of glia, mostly astrocytic. The astrocytic nature of most glioblastomas has been confirmed by ultrastructural studies and progressive differentiation of tumours maintained in organotypic tissue culture. Reproducible experimental models are particularly induced by oncogenic RNA (oncorna) viruses. The cell kinetic parameters are similar to those of other solid malignant tumours except for a comparatively low growth fraction of glioblastoma. The frequent occurrence of giant cells as well as of regressive changes with necrosis and vascular responses are indirect (secondary) indicators of malignancy which coincide with histochemical (enzymatic anisochronia) and biochemical data (lower level of glia specific S100 protein than in differentiated gliomas). Vascular proliferation, a characteristic feature of glioblastoma, may occasionally progress to sarcomatous transformation with development of gliosarcomas (mixed glial-mesenchymal tumours). While dissemination of glioblastoma through the cerebrospinal pathways is not uncommon, extraneural distant metastatic spread is rare, and usually observed after craniotomy. The results of modern neuro-oncology support the pathogenetic view that glioblastoma results from neoplastic transformation of glial elements with continuing dedifferentiation. This transformation can be experimentally induced by various factors including oncogenic DNA (oncorna) viruses by using a reverse transcriptase, while there is indirect evidence for an oncorna-virus information in human glioblastoma. The significance of immunological factors in the pathogenesis of brain tumours and in the course of neoplastic transformation of glia is not yet understood, but both morphological and immunological data are in favour of a cell mediated immunological reaction against tumour-specific antibodies. Since immunological factors and changes in cytokinetics are apparently active after the transformed tumour cells proliferate, all available therapeutic methods, including radiation, chemotherapy, and immunotherapy of glioblastoma only influence the final stages of neoplastic development with clinical manifestation of the tumour. In spite of modern combination and multimodality therapy schemes the prognosis of glioblastoma is still poor."}
{"id": "PMID:211810", "title": "Megavoltage therapy of glioblastoma multiforme.", "content": "Supervolt radiation therapy produced no improved survival rates in the treatment of glioblastoma multiforme as compared to orthovolt therapy. Survival times of more than one year or two years must still be considered a rarity. The application of computer techniques to the calculation of dose distributions greatly enhances the optimization of treatment planning. Tumour doses of 5,000 to 7,000 rad are considered necessary, and are dangerously close to the dose levels tolerated by brain tissue. Improvements could conceivably be expected from a) combinations of chemotherapy and radiation therapy, b) intra-arterial application of radiating substances with tumour affinity, c) neutron therapy. Whether or not such measures will in the future produce improved therapeutic results remains to be seen.", "contents": "Megavoltage therapy of glioblastoma multiforme. Supervolt radiation therapy produced no improved survival rates in the treatment of glioblastoma multiforme as compared to orthovolt therapy. Survival times of more than one year or two years must still be considered a rarity. The application of computer techniques to the calculation of dose distributions greatly enhances the optimization of treatment planning. Tumour doses of 5,000 to 7,000 rad are considered necessary, and are dangerously close to the dose levels tolerated by brain tissue. Improvements could conceivably be expected from a) combinations of chemotherapy and radiation therapy, b) intra-arterial application of radiating substances with tumour affinity, c) neutron therapy. Whether or not such measures will in the future produce improved therapeutic results remains to be seen."}
{"id": "PMID:211811", "title": "Multicentric glioblastomas. Methods of diagnosis and treatment.", "content": "Although multicentric glioblastomas are relatively rare, their occurrence is not an extreme rarity. A multicentric lesion should always be thought of when the symptoms cannot be related to a single focus and when the special investigations do not confirm a single lesion. In our opinion the brain scintigram and the computer tomogram offer the best diagnostic possibilities at present. If the preoperative diagnosis has been made, then an indication for operation can be justified only if multiple tumours can be removed through one approach and, what is even more important, at one sitting. The cases demonstrated prove that this procedure can be successful. If, on the other hand, only one of several tumours is excised, then a fatal outcome is almost certain.", "contents": "Multicentric glioblastomas. Methods of diagnosis and treatment. Although multicentric glioblastomas are relatively rare, their occurrence is not an extreme rarity. A multicentric lesion should always be thought of when the symptoms cannot be related to a single focus and when the special investigations do not confirm a single lesion. In our opinion the brain scintigram and the computer tomogram offer the best diagnostic possibilities at present. If the preoperative diagnosis has been made, then an indication for operation can be justified only if multiple tumours can be removed through one approach and, what is even more important, at one sitting. The cases demonstrated prove that this procedure can be successful. If, on the other hand, only one of several tumours is excised, then a fatal outcome is almost certain."}
{"id": "PMID:211822", "title": "Protein heterogeneity in rat CNS myelin subfractions.", "content": "Microsomal fraction-free myelin from forebrain and spinal cord of young and mature rats, when subjected to hypo-osmotic shock and slow speed centrifugation, yielded a myelin pellet and a supernatant fraction (SN 4). Fraction SN 4 consisted of small vesicular profiles in which the major myelin proteins were reduced whereas high molecular weight material such as Wolfgram protein, myelin-associated glycoprotein and CNP were substantially increased over myelin. A close correlation of the SN 4 fraction to the myelin-like fraction of Davison and coworkers was suggested. The myelin pellets were subfractioned on zonal sucrose gradients to yield bell-shaped particle distributions. Besides shifts in densities of the maxima between myelin of young and mature forebrain and spinal cord, a decrease was observed from the light to the heavy gradient end in basic proteins, and an increase in Wolfgram protein and other high molecular weight proteins. Proteolipid protein took an intermediate position. Light fractions from adult spinal cord displayed CNP activities below those of the total homogenate. This result, together with the very high CNP activities in fraction SN 4 casts some doubt on CNP being a marker for compact myelin; rather it appears that CNP is a marker for the process of myelin formation.", "contents": "Protein heterogeneity in rat CNS myelin subfractions. Microsomal fraction-free myelin from forebrain and spinal cord of young and mature rats, when subjected to hypo-osmotic shock and slow speed centrifugation, yielded a myelin pellet and a supernatant fraction (SN 4). Fraction SN 4 consisted of small vesicular profiles in which the major myelin proteins were reduced whereas high molecular weight material such as Wolfgram protein, myelin-associated glycoprotein and CNP were substantially increased over myelin. A close correlation of the SN 4 fraction to the myelin-like fraction of Davison and coworkers was suggested. The myelin pellets were subfractioned on zonal sucrose gradients to yield bell-shaped particle distributions. Besides shifts in densities of the maxima between myelin of young and mature forebrain and spinal cord, a decrease was observed from the light to the heavy gradient end in basic proteins, and an increase in Wolfgram protein and other high molecular weight proteins. Proteolipid protein took an intermediate position. Light fractions from adult spinal cord displayed CNP activities below those of the total homogenate. This result, together with the very high CNP activities in fraction SN 4 casts some doubt on CNP being a marker for compact myelin; rather it appears that CNP is a marker for the process of myelin formation."}
{"id": "PMID:211823", "title": "Retardation of brain myelination by malnourishment and feeding low protein irradiated diet in rats.", "content": "The effect of feeding low protein diet, and the low protein irradiated diet on the deposition of myelin in the brains of rats over two generations showed that malnourishment lowered the CNP enzyme activity when compared to the normal (high protein) diet fed control rats during early postnatal period. Irradiated low protein diet, when fed within 21 days of irradiaton (15 Krads Gamma radiation, 60Co rays), produced still lower CNP enzyme activity. This also enhanced other effects of retarding the brain development, by lowering the protein and lipid contents of the brain during a period from the 4th to 25th day of postnatal development. This suggests the possibility that feeding irradiated low protein food to malnourished developing mammals could cause serious problems like mental retardation.", "contents": "Retardation of brain myelination by malnourishment and feeding low protein irradiated diet in rats. The effect of feeding low protein diet, and the low protein irradiated diet on the deposition of myelin in the brains of rats over two generations showed that malnourishment lowered the CNP enzyme activity when compared to the normal (high protein) diet fed control rats during early postnatal period. Irradiated low protein diet, when fed within 21 days of irradiaton (15 Krads Gamma radiation, 60Co rays), produced still lower CNP enzyme activity. This also enhanced other effects of retarding the brain development, by lowering the protein and lipid contents of the brain during a period from the 4th to 25th day of postnatal development. This suggests the possibility that feeding irradiated low protein food to malnourished developing mammals could cause serious problems like mental retardation."}
{"id": "PMID:211824", "title": "On the accessibility and localisation of cerebrosides in central nervous system myelin.", "content": "Cerebrosides are concentrated in the myelin sheath where they account for about 20% of the total lipid of the membrane. The present paper is concerned with the role and localisation of these glycolipids in the myelin lamellae. Isolated central nerve myelin preparations have been treated with two probes to investigate cerebroside accessibility in the membrane. The action of galactose oxidase on the galactose headgroups of cerebrosides is followed and quantitated by recovery of the modified glycolipid and resolution of either the 6-aldehydo sugar or galactose remaining by gas-liquid chromatography. With isolated myelin preparations only some 40--50% of the cerebroside galactose is attacked by galactose oxidase at 20 degrees C. With periodate at 20 degrees C over 90% of the galactose headgroups are oxidised in 3 h while the figure is 50--55% over the same time period at 4 degrees C rising to 85% after 22 h. With multilamellar liposomes of mixed myelin lipids only some 20--25% of the available cerebroside is oxidised at 4 degrees C, the reaction being complete in 2 h. The results are discussed in relation to the dispositon of cerebroside in the myelin lamellae. A major location on the external face of the membrane system (intraperiod dense line) is favoured. A role for cerebroside in myelin in terms of increasing the stability and resistance of the lipid phase to ion movement is suggested.", "contents": "On the accessibility and localisation of cerebrosides in central nervous system myelin. Cerebrosides are concentrated in the myelin sheath where they account for about 20% of the total lipid of the membrane. The present paper is concerned with the role and localisation of these glycolipids in the myelin lamellae. Isolated central nerve myelin preparations have been treated with two probes to investigate cerebroside accessibility in the membrane. The action of galactose oxidase on the galactose headgroups of cerebrosides is followed and quantitated by recovery of the modified glycolipid and resolution of either the 6-aldehydo sugar or galactose remaining by gas-liquid chromatography. With isolated myelin preparations only some 40--50% of the cerebroside galactose is attacked by galactose oxidase at 20 degrees C. With periodate at 20 degrees C over 90% of the galactose headgroups are oxidised in 3 h while the figure is 50--55% over the same time period at 4 degrees C rising to 85% after 22 h. With multilamellar liposomes of mixed myelin lipids only some 20--25% of the available cerebroside is oxidised at 4 degrees C, the reaction being complete in 2 h. The results are discussed in relation to the dispositon of cerebroside in the myelin lamellae. A major location on the external face of the membrane system (intraperiod dense line) is favoured. A role for cerebroside in myelin in terms of increasing the stability and resistance of the lipid phase to ion movement is suggested."}
{"id": "PMID:211825", "title": "Virus infection in demyelinating diseases.", "content": "Several animal and human demyelinating diseases of the central nervous system (CNS) are associated with RNA or DNA viruses. These viruses infect CNS cells lytically or persistently. They mainly belong to the group of envelope viruses which derive their envelope partly from the host cell membrane. The process of virus release may result in the appearance of new antigens of virus-infected cells or the incorporation of cell membrane material into the viral envelope. These changes may lead to an immune response which selectively injures the CNS. These alterations of host cell membranes and host cell functions, together with the immune mechanism, are central to many of the hypotheses regarding virus-induced demyelination. The role of virus infection in progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, visna and mouse hepatitis virus infections, is discussed in relation to the demyelinating process of these diseases.", "contents": "Virus infection in demyelinating diseases. Several animal and human demyelinating diseases of the central nervous system (CNS) are associated with RNA or DNA viruses. These viruses infect CNS cells lytically or persistently. They mainly belong to the group of envelope viruses which derive their envelope partly from the host cell membrane. The process of virus release may result in the appearance of new antigens of virus-infected cells or the incorporation of cell membrane material into the viral envelope. These changes may lead to an immune response which selectively injures the CNS. These alterations of host cell membranes and host cell functions, together with the immune mechanism, are central to many of the hypotheses regarding virus-induced demyelination. The role of virus infection in progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, visna and mouse hepatitis virus infections, is discussed in relation to the demyelinating process of these diseases."}
{"id": "PMID:211826", "title": "Early and late CNS-effects of corona virus infection in rats.", "content": "The mouse hepatitis virus strain JHM was injected intracerebrally into newborn and weanling rats. Three types of diseases were observed: 1. Acute panencephalitis: Almost all suckling rats became moribund within 6 days. Histologically severe panencephalitis with demyelinating foci was noticed; the foci were similar to those found in mice. Virus was easily detectable in the oligodendroglial cells and neurons both by immunofluorescence and electron microscopy. Infectious virus could be isolated. 2. Subacute demyelinating encephalomyelitis (SDE): Three weeks after infection of weanling rats, about 35% of the animals developed paralysis. Neuropathologically, demyelination with a striking predilection for white matter was observed in the brain stem, optic nerve and spinal cord. Virus was detectable by electron microscopy in degenerating oligodendroglial cells only, which corresponded to the results obtained by the immunofluorescent techniques. Infectious virus could be recovered. 3. Chronic progressive paralysis: Inoculated weanling rats without SDE developed 6 to 8 months later a slowly progressing paralysis of the legs. Hydrocephalus and myelomalacia were present. Viral \"footprints\" could not be detected.", "contents": "Early and late CNS-effects of corona virus infection in rats. The mouse hepatitis virus strain JHM was injected intracerebrally into newborn and weanling rats. Three types of diseases were observed: 1. Acute panencephalitis: Almost all suckling rats became moribund within 6 days. Histologically severe panencephalitis with demyelinating foci was noticed; the foci were similar to those found in mice. Virus was easily detectable in the oligodendroglial cells and neurons both by immunofluorescence and electron microscopy. Infectious virus could be isolated. 2. Subacute demyelinating encephalomyelitis (SDE): Three weeks after infection of weanling rats, about 35% of the animals developed paralysis. Neuropathologically, demyelination with a striking predilection for white matter was observed in the brain stem, optic nerve and spinal cord. Virus was detectable by electron microscopy in degenerating oligodendroglial cells only, which corresponded to the results obtained by the immunofluorescent techniques. Infectious virus could be recovered. 3. Chronic progressive paralysis: Inoculated weanling rats without SDE developed 6 to 8 months later a slowly progressing paralysis of the legs. Hydrocephalus and myelomalacia were present. Viral \"footprints\" could not be detected."}
{"id": "PMID:211827", "title": "A search for the \"multiple sclerosis virus\"--lack of effect of brain extracts on myelin development in chickens, mice and rats.", "content": "Attempts were made to transmit possible infectious agents from tissue of MS patients into three animal species, under conditions designed to enhance the development of such an agent. Myelination was monitored by measuring CNPase activity and myelin basic protein. Although no significant effects were observed, the usefulness of a new assay for CNPase was demonstrated. Nude mice were found to have a lower level of CNPase than their heterozygous littermates.", "contents": "A search for the \"multiple sclerosis virus\"--lack of effect of brain extracts on myelin development in chickens, mice and rats. Attempts were made to transmit possible infectious agents from tissue of MS patients into three animal species, under conditions designed to enhance the development of such an agent. Myelination was monitored by measuring CNPase activity and myelin basic protein. Although no significant effects were observed, the usefulness of a new assay for CNPase was demonstrated. Nude mice were found to have a lower level of CNPase than their heterozygous littermates."}
{"id": "PMID:211838", "title": "Chemical and statistical studies of contaminants in urban lungs.", "content": "Lungs taken at autopsy from 100 urban residents were studied to determine concentrations of 21 trace metals, dust, free silica and hydroxyproline. Medical, occupational and environmental histories were collected so that correlation studies might be done. The potential value of this data as a baseline for further studies of occupationally diseased lung tissue was assessed by evaluating the results of an analysis of variance. The personal histories were used as the criteria for classifying the observations (lung concentrations) into groups for the statistical analysis.", "contents": "Chemical and statistical studies of contaminants in urban lungs. Lungs taken at autopsy from 100 urban residents were studied to determine concentrations of 21 trace metals, dust, free silica and hydroxyproline. Medical, occupational and environmental histories were collected so that correlation studies might be done. The potential value of this data as a baseline for further studies of occupationally diseased lung tissue was assessed by evaluating the results of an analysis of variance. The personal histories were used as the criteria for classifying the observations (lung concentrations) into groups for the statistical analysis."}
{"id": "PMID:211839", "title": "Nitrogen-containing compounds in foundry mold emissions.", "content": "Nitrogen compounds have been identified in the decomposition products from several commonly used foundry sand binders. These compounds include nitrogen oxides, hydrogen cyanide, ammonia, simple aromatic amines, and isocyanates. The concentrations of these compounds in foundry mold emissions do not appear to be directly related to the nitrogen content of the organic binders. Measurable concentrations were observed in some cases, indicating the necessity for periodic, monitoring in the foundry. Adequate ventilation will permit the use of these binders. The substitution of nitrogen-free binders suggests another possible control strategy.", "contents": "Nitrogen-containing compounds in foundry mold emissions. Nitrogen compounds have been identified in the decomposition products from several commonly used foundry sand binders. These compounds include nitrogen oxides, hydrogen cyanide, ammonia, simple aromatic amines, and isocyanates. The concentrations of these compounds in foundry mold emissions do not appear to be directly related to the nitrogen content of the organic binders. Measurable concentrations were observed in some cases, indicating the necessity for periodic, monitoring in the foundry. Adequate ventilation will permit the use of these binders. The substitution of nitrogen-free binders suggests another possible control strategy."}
{"id": "PMID:211840", "title": "Exposure of firefighters to toxic air contaminants.", "content": "A personal sampling apparatus for firefighters was developed to sample the fire atmosphere for CO, CO2, O2, NO2, HCI, HCN and pariculate content. Two fire companies made ninety successful sample runs during structural fires. CO presented a potential acute hazard and particulate concentrations were high. HCN was detected at low levels in half the samples. HCI was detected in only eight samples but on two occasions exceeded 100 ppm. CO2 and NO2 levels and O2 depression do not appear to represent significant hazards.", "contents": "Exposure of firefighters to toxic air contaminants. A personal sampling apparatus for firefighters was developed to sample the fire atmosphere for CO, CO2, O2, NO2, HCI, HCN and pariculate content. Two fire companies made ninety successful sample runs during structural fires. CO presented a potential acute hazard and particulate concentrations were high. HCN was detected at low levels in half the samples. HCI was detected in only eight samples but on two occasions exceeded 100 ppm. CO2 and NO2 levels and O2 depression do not appear to represent significant hazards."}
{"id": "PMID:211841", "title": "Hapten-specific respiratory hypersensitivity in guinea pigs.", "content": "Respiratory hypersensitivity to small chemical determinants (haptens) was produced in guinea pigs by repeatedly exposing the animals to aerosols of hapten-ovalbumin conjugates. In this way, reactivity toward p-azobenzenearsonate and p-tolyl isocyanate was induced. Carrier (ovalbumin)-specific respiratory reactions were not produced. Hapten-specific respiratory hypersensitivity was accompanied by the production of hapten-specific antibodies. The method for inducing hapten-specific hypersensitivity can be applied to screen various industrial chemicals for their sensitizing abilities toward the respiratory tract.", "contents": "Hapten-specific respiratory hypersensitivity in guinea pigs. Respiratory hypersensitivity to small chemical determinants (haptens) was produced in guinea pigs by repeatedly exposing the animals to aerosols of hapten-ovalbumin conjugates. In this way, reactivity toward p-azobenzenearsonate and p-tolyl isocyanate was induced. Carrier (ovalbumin)-specific respiratory reactions were not produced. Hapten-specific respiratory hypersensitivity was accompanied by the production of hapten-specific antibodies. The method for inducing hapten-specific hypersensitivity can be applied to screen various industrial chemicals for their sensitizing abilities toward the respiratory tract."}
{"id": "PMID:211842", "title": "Benign tumors of the liver. Pathologic examination of 45 cases.", "content": "The histologic and clinical features of 45 benign tumors of the liver (excluding hemangiomas) were reviewed. They included 21 cases of focal nodular hyperplasia, 11 cases of hepatic cell adenoma, 12 cases of bile-duct adenoma and a single case of mesenchymal hamartoma. By adhering to published histologic criteria, the cases of focal nodular hyperplasia and hepatic cell adenoma could be readily separated. Although both focal nodular hyperplasia and hepatic cell adenoma occurred predominantly in women, focal nodular hyperplasia occurred at a greater mean age, was usually asymptomatic, and the lesions tended to be smaller (surgical cases) than hepatic cell adenoma. The latter usually were symptomatic. It is emphasized that focal nodular hyperplasia and hepatic cell adenoma are distinct lesions and are separable on histologic grounds. Although the names focal nodular hyperplasia and hepatic cell adenoma are retained, the authors cannot assert that one lesion is a neoplasm, the other a reactive condition, and prefer, instead, to leave this question unresolved.", "contents": "Benign tumors of the liver. Pathologic examination of 45 cases. The histologic and clinical features of 45 benign tumors of the liver (excluding hemangiomas) were reviewed. They included 21 cases of focal nodular hyperplasia, 11 cases of hepatic cell adenoma, 12 cases of bile-duct adenoma and a single case of mesenchymal hamartoma. By adhering to published histologic criteria, the cases of focal nodular hyperplasia and hepatic cell adenoma could be readily separated. Although both focal nodular hyperplasia and hepatic cell adenoma occurred predominantly in women, focal nodular hyperplasia occurred at a greater mean age, was usually asymptomatic, and the lesions tended to be smaller (surgical cases) than hepatic cell adenoma. The latter usually were symptomatic. It is emphasized that focal nodular hyperplasia and hepatic cell adenoma are distinct lesions and are separable on histologic grounds. Although the names focal nodular hyperplasia and hepatic cell adenoma are retained, the authors cannot assert that one lesion is a neoplasm, the other a reactive condition, and prefer, instead, to leave this question unresolved."}
{"id": "PMID:211843", "title": "M\u00fcllerian adenosarcoma of the uterus. Ultrastructure before and after radiation therapy.", "content": "A case of m\u00fcllerian adenosarcoma arising in the endometrium was studied by light and electron microscopy before and after radiation treatment. The tumor was composed of malignant stroma containing undifferentiated mesenchymal cells admixed with mature fibroblasts and other cell that contained crystalloids. The surface epithelium was lined by epithelial cells with and without cilia, similar to the normal surface epithelium cells of the uterus. High-dose therapeutic irradiation eliminated the undifferentiated mesenchymal cells from the tumor but did not alter the morphology of other epithelial and mesenchymal elements. The immaturity of mesenchymal cells and their radiosensitivity coupled with the ultrasonographic evidence of growth of the tumor point to the probable malignant nature of this neoplasm.", "contents": "M\u00fcllerian adenosarcoma of the uterus. Ultrastructure before and after radiation therapy. A case of m\u00fcllerian adenosarcoma arising in the endometrium was studied by light and electron microscopy before and after radiation treatment. The tumor was composed of malignant stroma containing undifferentiated mesenchymal cells admixed with mature fibroblasts and other cell that contained crystalloids. The surface epithelium was lined by epithelial cells with and without cilia, similar to the normal surface epithelium cells of the uterus. High-dose therapeutic irradiation eliminated the undifferentiated mesenchymal cells from the tumor but did not alter the morphology of other epithelial and mesenchymal elements. The immaturity of mesenchymal cells and their radiosensitivity coupled with the ultrasonographic evidence of growth of the tumor point to the probable malignant nature of this neoplasm."}
{"id": "PMID:211844", "title": "Cystosarcoma phyllodes. A clinicopathologic study of twenty-six hypercellular periductal stromal tumors of the breast.", "content": "A series of 26 hypercellular periductal stromal tumors of the breast, commonly referred to as cystosarcoma phyllodes, is reported. Twelve neoplasms were classified histologically as benign and 14 (54%) as maligant after microscopic assessment of the stromal elements. None of the histologically benign cystosarcomas metastasized, although two recurred locally. Malignant transformation was not observed in the recurrent tumors. Local recurrences developed in four women with histologically malignant cystosarcomas and caused the death of one by direct extension into the lung. Pulmonary metastases of the sarcomatous element occurred in three. Two of these women died and one has survived 16 years after pulmonary lobectomy. Separation of cystosarcomas into benign and malignant categories on the basis of their histopathologic features is advocated. It is likely that overgrowth of the sarcomatous stroma is a prerequisite for metastasis.", "contents": "Cystosarcoma phyllodes. A clinicopathologic study of twenty-six hypercellular periductal stromal tumors of the breast. A series of 26 hypercellular periductal stromal tumors of the breast, commonly referred to as cystosarcoma phyllodes, is reported. Twelve neoplasms were classified histologically as benign and 14 (54%) as maligant after microscopic assessment of the stromal elements. None of the histologically benign cystosarcomas metastasized, although two recurred locally. Malignant transformation was not observed in the recurrent tumors. Local recurrences developed in four women with histologically malignant cystosarcomas and caused the death of one by direct extension into the lung. Pulmonary metastases of the sarcomatous element occurred in three. Two of these women died and one has survived 16 years after pulmonary lobectomy. Separation of cystosarcomas into benign and malignant categories on the basis of their histopathologic features is advocated. It is likely that overgrowth of the sarcomatous stroma is a prerequisite for metastasis."}
{"id": "PMID:211845", "title": "Decreased angiotensin-converting enzyme in the adult respiratory distress syndrome.", "content": "Using hippuryl-L-histidyl-L-leucine as substrate, serum angiotensin-converting enzyme was measured in 13 patients who had adult respiratory distress syndrome, eight patients with respiratory failure without adult respiratory distress syndrome, and two groups of controls: 24 healthy blood donors and 24 hospitalized patients with a variety of conditions but without respiratory failure or adult respiratory distress syndrome. Serum angiotensin-converting enzyme expressed in units/ml was 14.60 +/- 5.60 for adult respiratory distress syndrome compared with 28.92 +/- 6.60 for the blood donors, 20.76 +/- 5.87 for the patients with respiratory failure without adult respiratory distress syndrome and 20.20 +/- 5.94 in the hospitalized patients without respiratory failure or adult respiratory distress syndrome. These differences were significant, P less than .001 when adult respiratory distress syndrome was tested against the blood donors and P less than .01 against the other two groups. The significance of these findings is not clear, but the possibility is raised that the decrease of angiotensin-converting enzyme in adult respiratory distress syndrome results from a loss of pulmonary endothelial cells, which are known both to produce angiotensin-converting enzyme and to be damaged in adult respiratory distress syndrome.", "contents": "Decreased angiotensin-converting enzyme in the adult respiratory distress syndrome. Using hippuryl-L-histidyl-L-leucine as substrate, serum angiotensin-converting enzyme was measured in 13 patients who had adult respiratory distress syndrome, eight patients with respiratory failure without adult respiratory distress syndrome, and two groups of controls: 24 healthy blood donors and 24 hospitalized patients with a variety of conditions but without respiratory failure or adult respiratory distress syndrome. Serum angiotensin-converting enzyme expressed in units/ml was 14.60 +/- 5.60 for adult respiratory distress syndrome compared with 28.92 +/- 6.60 for the blood donors, 20.76 +/- 5.87 for the patients with respiratory failure without adult respiratory distress syndrome and 20.20 +/- 5.94 in the hospitalized patients without respiratory failure or adult respiratory distress syndrome. These differences were significant, P less than .001 when adult respiratory distress syndrome was tested against the blood donors and P less than .01 against the other two groups. The significance of these findings is not clear, but the possibility is raised that the decrease of angiotensin-converting enzyme in adult respiratory distress syndrome results from a loss of pulmonary endothelial cells, which are known both to produce angiotensin-converting enzyme and to be damaged in adult respiratory distress syndrome."}
{"id": "PMID:211846", "title": "Oral and intrauterine contraception: a 1978 risk assessment.", "content": "This report reviews the current literature on the various risks associated with the use of oral contraceptives and intrauterine contraceptive devices. Reports on oral contraceptives from large prospective studies are not beginning to supplement the detailed reports resulting from earlier case-control studies. These studies suggest that in Western societies there is an increase in the incidence of a variety of circulatory diseases, with an increased risk of death. With intrauterine contraceptive devices it now has been fairly well documented that there is an increased risk of pelvic inflammatory disease. After reviewing and assessing the risks of both methods in some detail and comparing these risks to the benefits, the resultant conclusion is that the benefits continue to outweigh the risks for both methods, except for older women who choose oral contraceptives and also are heavy smokers.", "contents": "Oral and intrauterine contraception: a 1978 risk assessment. This report reviews the current literature on the various risks associated with the use of oral contraceptives and intrauterine contraceptive devices. Reports on oral contraceptives from large prospective studies are not beginning to supplement the detailed reports resulting from earlier case-control studies. These studies suggest that in Western societies there is an increase in the incidence of a variety of circulatory diseases, with an increased risk of death. With intrauterine contraceptive devices it now has been fairly well documented that there is an increased risk of pelvic inflammatory disease. After reviewing and assessing the risks of both methods in some detail and comparing these risks to the benefits, the resultant conclusion is that the benefits continue to outweigh the risks for both methods, except for older women who choose oral contraceptives and also are heavy smokers."}
{"id": "PMID:211849", "title": "Phagocytosis by cells of the pulmonary alveoli. Transformation of crystalline particles.", "content": "The progressive transformation of illite crystals in alveolar macrophages has been studied with x-ray microanalysis and electron microdiffraction. Illite particles captured by macrophages undergo a series of progressive modifications which affect their ultrastructure, crystalline state, and chemical composition. Crystalline structure progressively disappears and certain elements are eliminated. At the end of the experiment, which lasted more than 6 months, the initial characteristics of the particles were greatly transformed. The constitutive elements of the illite particles were also found in structures other than macrophages: Type I pneumocytes, interstitium, and blood platelets.", "contents": "Phagocytosis by cells of the pulmonary alveoli. Transformation of crystalline particles. The progressive transformation of illite crystals in alveolar macrophages has been studied with x-ray microanalysis and electron microdiffraction. Illite particles captured by macrophages undergo a series of progressive modifications which affect their ultrastructure, crystalline state, and chemical composition. Crystalline structure progressively disappears and certain elements are eliminated. At the end of the experiment, which lasted more than 6 months, the initial characteristics of the particles were greatly transformed. The constitutive elements of the illite particles were also found in structures other than macrophages: Type I pneumocytes, interstitium, and blood platelets."}
{"id": "PMID:211848", "title": "Cell biology of leukocyte abnormalities--membrane and cytoskeletal function in normal and defective cells. A review.", "content": "In this review I have attempted to explain the processes of chemotaxis, phagocytosis, oxidant generation, and lysosomal degranulation in normal and genetically abnormal human PMN. In my view these leukocyte functions are most importantly dependent on the integrity of three cellular components: the plasma membrane, the submembranous microfilaments, and the cytoplasmic microtubules. These components are often discussed in isolation, and the biochemical and pharmacological aspects of their function are analyzed separately here. However, PMN motile and bactericidal activities require the interdependent functioning of membranes, microtubules, and microfilaments. I have therefore tried to provide an integrated view of cytoskeleton-membrane organization and function in human PMN. I have particularly emphasized dynamic aspects of the cytoskeleton and membranes, eg, the induction of microtubule assembly and membrane enzyme activation by surface ligands and the reorganization of microfilaments in response to the same ligands. With this background established, I have selected for discussion a series of diseases in which abnormalities of chemotaxis, phagocytosis, lysosomal degranulation, and/or oxidant generation can be explained directly or indirectly by abnormalities in dynamic properties of PMN membranes, microtubules, or microfilaments. I emphasize that even preliminary insight into the basis of these disorders has sometimes been sufficient to suggest useful clinical approaches to the management of patients. In several of these neutrophil abnormalities, ie, neutrophil actin dysfunction, Ch\u00e9diak-Higashi syndrome, and its \"antithesis\" described by Gallin and co-workers, the cellular dysfunctions were well documented but the molecular basis was completely obscure prior to cell biologic analysis. Snyderman and Pike 159 and Chusid and co-workers 160 emphasized the existence of a large number of other neutrophil bactericidal abnormalities resulting from as yet unexplained cellular defects. Further analyses of the functional interactions between membranes and cytoskeletal components in neutrophils may not only clarify the molecular bases of the disorders described here but also may provide insight into the origins and proper therapeutic approach to other granulocyte dysfunctions.", "contents": "Cell biology of leukocyte abnormalities--membrane and cytoskeletal function in normal and defective cells. A review. In this review I have attempted to explain the processes of chemotaxis, phagocytosis, oxidant generation, and lysosomal degranulation in normal and genetically abnormal human PMN. In my view these leukocyte functions are most importantly dependent on the integrity of three cellular components: the plasma membrane, the submembranous microfilaments, and the cytoplasmic microtubules. These components are often discussed in isolation, and the biochemical and pharmacological aspects of their function are analyzed separately here. However, PMN motile and bactericidal activities require the interdependent functioning of membranes, microtubules, and microfilaments. I have therefore tried to provide an integrated view of cytoskeleton-membrane organization and function in human PMN. I have particularly emphasized dynamic aspects of the cytoskeleton and membranes, eg, the induction of microtubule assembly and membrane enzyme activation by surface ligands and the reorganization of microfilaments in response to the same ligands. With this background established, I have selected for discussion a series of diseases in which abnormalities of chemotaxis, phagocytosis, lysosomal degranulation, and/or oxidant generation can be explained directly or indirectly by abnormalities in dynamic properties of PMN membranes, microtubules, or microfilaments. I emphasize that even preliminary insight into the basis of these disorders has sometimes been sufficient to suggest useful clinical approaches to the management of patients. In several of these neutrophil abnormalities, ie, neutrophil actin dysfunction, Ch\u00e9diak-Higashi syndrome, and its \"antithesis\" described by Gallin and co-workers, the cellular dysfunctions were well documented but the molecular basis was completely obscure prior to cell biologic analysis. Snyderman and Pike 159 and Chusid and co-workers 160 emphasized the existence of a large number of other neutrophil bactericidal abnormalities resulting from as yet unexplained cellular defects. Further analyses of the functional interactions between membranes and cytoskeletal components in neutrophils may not only clarify the molecular bases of the disorders described here but also may provide insight into the origins and proper therapeutic approach to other granulocyte dysfunctions."}
{"id": "PMID:211850", "title": "Ultrastructure of nitrosoheptamethyleneimine-induced lung tumors in European hamsters.", "content": "The ultrastructure of lung tumors induced in European hamsters through chronic subcutaneous treatment with nitrosoheptamethyleneimine (NHMI) is described. The neoplasms demonstrated either adenomatous (adenomas and adenocarcinomas) or mixed (tumors with areas of adenoid and squamous differentiation) pattern. Adenomatous areas consisted of Clara cells and of cells with lamellated inclusion bodies in their cytoplasm. Cells in areas with squamous differentiation contained cytoplasmic filaments and filament bundles as well as dense-cored granules.", "contents": "Ultrastructure of nitrosoheptamethyleneimine-induced lung tumors in European hamsters. The ultrastructure of lung tumors induced in European hamsters through chronic subcutaneous treatment with nitrosoheptamethyleneimine (NHMI) is described. The neoplasms demonstrated either adenomatous (adenomas and adenocarcinomas) or mixed (tumors with areas of adenoid and squamous differentiation) pattern. Adenomatous areas consisted of Clara cells and of cells with lamellated inclusion bodies in their cytoplasm. Cells in areas with squamous differentiation contained cytoplasmic filaments and filament bundles as well as dense-cored granules."}
{"id": "PMID:211851", "title": "Reactive forms of oxygen and chemiluminescence in phagocytizing rabbit alveolar macrophages.", "content": "Chemiluminescence (CL), superoxide anion (O2-) production, and particle uptake were measured to determine the role of antibacterial substances in the chemiluminescent response associated with phagocytosis in rabbit alveolar macrophages (AM). Exposure of AM to zymosan particles induced both CL and the production of extracellular O2-. CL is inhibited by superoxide dismutase, an enzyme which catalyzes the conversion of O2- to hydrogen peroxide (H2O2), by catalase, an enzyme which destroys H2O2, and by the hydroxyl radical (.OH) scavengers, benzoate and ethanol. Superoxide dismutase and catalase probably exert their effects in the extracellular fluid. CL can also be produced by the addition of NaO2 or H2O2 to zymosan in a noncellular system. The chemiluminescent response occurs before particle uptake is complete, which also indicates that CL occurs in the extracellular fluid. These results suggest that CL induced by zymosan in AM is due to the extracellular reaction between various reactive forms of oxygen and zymosan.", "contents": "Reactive forms of oxygen and chemiluminescence in phagocytizing rabbit alveolar macrophages. Chemiluminescence (CL), superoxide anion (O2-) production, and particle uptake were measured to determine the role of antibacterial substances in the chemiluminescent response associated with phagocytosis in rabbit alveolar macrophages (AM). Exposure of AM to zymosan particles induced both CL and the production of extracellular O2-. CL is inhibited by superoxide dismutase, an enzyme which catalyzes the conversion of O2- to hydrogen peroxide (H2O2), by catalase, an enzyme which destroys H2O2, and by the hydroxyl radical (.OH) scavengers, benzoate and ethanol. Superoxide dismutase and catalase probably exert their effects in the extracellular fluid. CL can also be produced by the addition of NaO2 or H2O2 to zymosan in a noncellular system. The chemiluminescent response occurs before particle uptake is complete, which also indicates that CL occurs in the extracellular fluid. These results suggest that CL induced by zymosan in AM is due to the extracellular reaction between various reactive forms of oxygen and zymosan."}
{"id": "PMID:211852", "title": "Binding of aldosterone to cytoplasmic and nuclear receptors of the urinary bladder epithelium of Bufo marinus.", "content": "Binding of aldosterone to cytoplasmic and nuclear sites in urinary bladder epithelia of Bufo marinus (Dominican variant) is saturable and dependent upon steroid concentration. Scatchard analysis of specific cytoplasmic binding yielded a maximal binding capacity (N) of 14.5 X 10(-14) mol/mg protein and an apparent equilibrium dissociation constant (Kd) of 1.4 X 10(-8) M. Since Scatchard analysis of specific nuclear binding was complex, this binding was resolved by a computer-generated cirve-fitting technique which analyzed total aldosterone bound. Nuclear binding was resolved into three sites: a nonsaturable site that was linearly dependent upon aldosterone concentration, and two saturable sites (types I and II). Type I sites had relatively low capacity for aldosterone (N = 31 +/- 1 X 10(-14) mol/mg DNA) and high affinity (Kd = 2.5 +/- 0.5 X 10(-9 M); tffininty (Kd = 8.6 +/- 1.7 X 10(-7) M). Competition for [3H]aldosterone binding by dexamethasone, corticosterone, cortisol, progesterone, testosterone, and 17 beta-estradiol demonstrated that type I nuclear sites have higher affinity for aldosterone than for other steroids. The findings are consistent with the inference that the type I site is the mineralocorticoid receptor.", "contents": "Binding of aldosterone to cytoplasmic and nuclear receptors of the urinary bladder epithelium of Bufo marinus. Binding of aldosterone to cytoplasmic and nuclear sites in urinary bladder epithelia of Bufo marinus (Dominican variant) is saturable and dependent upon steroid concentration. Scatchard analysis of specific cytoplasmic binding yielded a maximal binding capacity (N) of 14.5 X 10(-14) mol/mg protein and an apparent equilibrium dissociation constant (Kd) of 1.4 X 10(-8) M. Since Scatchard analysis of specific nuclear binding was complex, this binding was resolved by a computer-generated cirve-fitting technique which analyzed total aldosterone bound. Nuclear binding was resolved into three sites: a nonsaturable site that was linearly dependent upon aldosterone concentration, and two saturable sites (types I and II). Type I sites had relatively low capacity for aldosterone (N = 31 +/- 1 X 10(-14) mol/mg DNA) and high affinity (Kd = 2.5 +/- 0.5 X 10(-9 M); tffininty (Kd = 8.6 +/- 1.7 X 10(-7) M). Competition for [3H]aldosterone binding by dexamethasone, corticosterone, cortisol, progesterone, testosterone, and 17 beta-estradiol demonstrated that type I nuclear sites have higher affinity for aldosterone than for other steroids. The findings are consistent with the inference that the type I site is the mineralocorticoid receptor."}
{"id": "PMID:211853", "title": "Aldosterone receptor occupancy and sodium transport in the urinary bladder of Bufo marinus.", "content": "The concentration dependence of binding of [3H]aldosterone to cytoplasmic and nuclear receptors was evaluated in urinary bladder epithelial cells of Colombian toads. One class of specific sites (sensitive to displacement by excess aldosterone) was detected in the cytosol. However, two classes of specific nuclear [3H]aldosterone binding sites were evident. In the nucleus, high-affinity (Kd = 2.7 X 10(-9) M), low-capacity (N = 15 X 10(-14) mol/mg DNA) sites (type I) were completely saturated at approximately 4 X 10(-8) M aldosterone, a concentration which gave a maximal increase in short-circuit current (SCC). Occupancy of low-affinity (Kd = 4.6 X 10(-7) M), high-capacity sites (N = 150 X 10(-14) mol/mg DNA) (type II) occurred at higher steroid concentrations and did not correlate with further increase in SCC. Binding parameters of Colombian and Dominican variants of Bufo marinus were compared. In both variants, the SCC increase elicited by aldosterone correlated with accumulation of type I complexes in the nucleus, but the relationship was markedly nonlinear. Various alternatives were considered as the basis for a curvilinear dependence of the increment in Na+ transport on abundance of nuclear type I complexes.", "contents": "Aldosterone receptor occupancy and sodium transport in the urinary bladder of Bufo marinus. The concentration dependence of binding of [3H]aldosterone to cytoplasmic and nuclear receptors was evaluated in urinary bladder epithelial cells of Colombian toads. One class of specific sites (sensitive to displacement by excess aldosterone) was detected in the cytosol. However, two classes of specific nuclear [3H]aldosterone binding sites were evident. In the nucleus, high-affinity (Kd = 2.7 X 10(-9) M), low-capacity (N = 15 X 10(-14) mol/mg DNA) sites (type I) were completely saturated at approximately 4 X 10(-8) M aldosterone, a concentration which gave a maximal increase in short-circuit current (SCC). Occupancy of low-affinity (Kd = 4.6 X 10(-7) M), high-capacity sites (N = 150 X 10(-14) mol/mg DNA) (type II) occurred at higher steroid concentrations and did not correlate with further increase in SCC. Binding parameters of Colombian and Dominican variants of Bufo marinus were compared. In both variants, the SCC increase elicited by aldosterone correlated with accumulation of type I complexes in the nucleus, but the relationship was markedly nonlinear. Various alternatives were considered as the basis for a curvilinear dependence of the increment in Na+ transport on abundance of nuclear type I complexes."}
{"id": "PMID:211855", "title": "Sex difference in LH response to LHRH and DBcAMP and effect of testosterone.", "content": "Because luteinizing hormone-releasing hormone (LHRH) stimulates both pituitary cAMP production and LH release, cAMP has been implicated in the action of LHRH on LH release. The effects of LHRH and DBcAMP on LH release were tested in 4-h incubations with pituitary cultures prepared from male or female rats. LH contents in medium and cells were separately determined by radioimmunoassays. LH release in response to 10 nM LHRH was significantly greater in cultures prepared from female rats (female-RPC) than in cultures prepared from male rats (male-RPC), 1,070 and 418% of control, respectively. Addition of DBcAMP (3, 5, or 10 mM) significantly stimulated LH release by female-RPC (212, 206, or 286% of control, respectively) but did not affect LH release in male-RPC. Furthermore, DBcAMP significantly increased the cellular LH content in female- but not in male-RPC. Testosterone pretreatment of female-RPC significantly lowered the LHRH-induced LH release but did not affect the DBcAMP-induced LH release. These data indicate that testosterone may contribute to the sex difference in pituitary LH response to LHRH but not to DBcAMP.", "contents": "Sex difference in LH response to LHRH and DBcAMP and effect of testosterone. Because luteinizing hormone-releasing hormone (LHRH) stimulates both pituitary cAMP production and LH release, cAMP has been implicated in the action of LHRH on LH release. The effects of LHRH and DBcAMP on LH release were tested in 4-h incubations with pituitary cultures prepared from male or female rats. LH contents in medium and cells were separately determined by radioimmunoassays. LH release in response to 10 nM LHRH was significantly greater in cultures prepared from female rats (female-RPC) than in cultures prepared from male rats (male-RPC), 1,070 and 418% of control, respectively. Addition of DBcAMP (3, 5, or 10 mM) significantly stimulated LH release by female-RPC (212, 206, or 286% of control, respectively) but did not affect LH release in male-RPC. Furthermore, DBcAMP significantly increased the cellular LH content in female- but not in male-RPC. Testosterone pretreatment of female-RPC significantly lowered the LHRH-induced LH release but did not affect the DBcAMP-induced LH release. These data indicate that testosterone may contribute to the sex difference in pituitary LH response to LHRH but not to DBcAMP."}
{"id": "PMID:211856", "title": "Influence of estrogen on renal vitamin D hydroxylases and serum 1alpha,25-(OH)2D3 in chicks.", "content": "The influence of estrogen on the metabolism of 25-hydroxyvitamin D3 was studied in 2- to 5-wk-old chicks. Single injections of at least 500 microgram diethylstibestrol (DES) increased the conversion of 25-hydroxyvitamin D3 to 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) and suppressed the production of 24,25-dihydroxyvitamin D3 in chick kidney homogenates. Acute (one 5-mg) injections of testosterone or progesterone did not enhance the 25-hydroxyvitamin D3-1alpha-hydroxylase, indicating specificity. However, chronic pretreatment with DES appeared to allow the potentiation of previously unstimulatory steroids such as progesterone and testosterone. In addition, the hormonal metabolite of vitamin D3, 1alpha,25-(OH)2D3, was measured in 4- to 6-wk chick plasma after steroid treatment. Greater than 1 mg DES per day for 5 days was necessary to enhance the circulating level of 1alpha,25-(OH)2D3; testosterone alone had no effect. This elevation was rapid, occurring within 12--24 h after injection. These data suggest that estrogen (as evidenced by DES treatment) is a modulator of vitamin D metabolism along with other known regulators such as parathyroid hormone, phosphate, and 1alpha,25-(OH)2D3. The mechanism of the regulation is as yet unknown.", "contents": "Influence of estrogen on renal vitamin D hydroxylases and serum 1alpha,25-(OH)2D3 in chicks. The influence of estrogen on the metabolism of 25-hydroxyvitamin D3 was studied in 2- to 5-wk-old chicks. Single injections of at least 500 microgram diethylstibestrol (DES) increased the conversion of 25-hydroxyvitamin D3 to 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) and suppressed the production of 24,25-dihydroxyvitamin D3 in chick kidney homogenates. Acute (one 5-mg) injections of testosterone or progesterone did not enhance the 25-hydroxyvitamin D3-1alpha-hydroxylase, indicating specificity. However, chronic pretreatment with DES appeared to allow the potentiation of previously unstimulatory steroids such as progesterone and testosterone. In addition, the hormonal metabolite of vitamin D3, 1alpha,25-(OH)2D3, was measured in 4- to 6-wk chick plasma after steroid treatment. Greater than 1 mg DES per day for 5 days was necessary to enhance the circulating level of 1alpha,25-(OH)2D3; testosterone alone had no effect. This elevation was rapid, occurring within 12--24 h after injection. These data suggest that estrogen (as evidenced by DES treatment) is a modulator of vitamin D metabolism along with other known regulators such as parathyroid hormone, phosphate, and 1alpha,25-(OH)2D3. The mechanism of the regulation is as yet unknown."}
{"id": "PMID:211857", "title": "Cardiovascular responses to blockade of angiotensin and alpha-adrenergic receptors.", "content": "Both angiotensin and alpha-adrenergic blocking agents reduce arterial blood pressure in hypovolemic states. We have compared the effects of an angiotensin antagonist (saralasin) and an alpha-adrenergic blocking agent (phenoxybenzamine) in supramaximal dosage on cardiac output, total peripheral resistance, and venous tone in rabbits rendered hypovolemic by restriction of sodium intake, supplemented by a furosemide-induced diuresis 48 h prior to study. Saralasin (10 microgram/kg per min) reduced arterial blood pressure significantly (-15 +/- 1.2 mmHg) despite an unchanged cardiac output (P less than 0.025) due to a fall in total peripheral resistance. Phenoxybenzamine (5 mg/kg) induced a much larger fall in arterial blood pressure (-28 +/- 3.6 mmHg), despite an identical reduction in total peripheral resistance, because cardiac output also fell (+/- 9 ml/kg per min). The reduction in cardiac output was associated with a significant increase in hindlimb venous distensibility (P less than 0.001) after alpha-adrenergic blockade. Saralasin, conversely, had no influence on venous tone. Adrenergic mechanisms contribute to cardiovascular homeostasis through an influence on both arteriolar and venous tone, whereas the effect of angiotensin is directed entirely to the arteriolar side of the circulation.", "contents": "Cardiovascular responses to blockade of angiotensin and alpha-adrenergic receptors. Both angiotensin and alpha-adrenergic blocking agents reduce arterial blood pressure in hypovolemic states. We have compared the effects of an angiotensin antagonist (saralasin) and an alpha-adrenergic blocking agent (phenoxybenzamine) in supramaximal dosage on cardiac output, total peripheral resistance, and venous tone in rabbits rendered hypovolemic by restriction of sodium intake, supplemented by a furosemide-induced diuresis 48 h prior to study. Saralasin (10 microgram/kg per min) reduced arterial blood pressure significantly (-15 +/- 1.2 mmHg) despite an unchanged cardiac output (P less than 0.025) due to a fall in total peripheral resistance. Phenoxybenzamine (5 mg/kg) induced a much larger fall in arterial blood pressure (-28 +/- 3.6 mmHg), despite an identical reduction in total peripheral resistance, because cardiac output also fell (+/- 9 ml/kg per min). The reduction in cardiac output was associated with a significant increase in hindlimb venous distensibility (P less than 0.001) after alpha-adrenergic blockade. Saralasin, conversely, had no influence on venous tone. Adrenergic mechanisms contribute to cardiovascular homeostasis through an influence on both arteriolar and venous tone, whereas the effect of angiotensin is directed entirely to the arteriolar side of the circulation."}
{"id": "PMID:211858", "title": "Distribution along the rat nephron of three enzymes of gluconeogenesis in acidosis and starvation.", "content": "Methods were devised or modified which made it possible to measure phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase in seven defined parts of single nephrons and in patches from thin limb and papilla areas dissected from freeze-dried microtome sections of rat kidney. All three enzymes were essentially confined to the proximal tubule. In normal kidneys, the levels were highest in the proximal convoluted tubule. Glucose-6-phosphatase was 20 times higher in the early part of the convoluted segment than in the late part of the straight segment. With one exception, in acidosis, only phosphoenolpyruvate carboxykinase increased (fourfold in the proximal convoluted segment but much less in the straight portion). In starvation, phosphoenolpyruvate carboxykinase increased about as much as in acidosis in the proximal straight tubule, but not as much in convoluted portions, whereas glucose-6-phosphatase rose modestly in both parts of the proximal tubule and fructose bisphosphatase rose only in the straight tubule, especially the early segment. It is suggested that ammoniagenesis can accompany gluconeogenesis in the proximal convoluted tubule but not in the straight segment.", "contents": "Distribution along the rat nephron of three enzymes of gluconeogenesis in acidosis and starvation. Methods were devised or modified which made it possible to measure phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase in seven defined parts of single nephrons and in patches from thin limb and papilla areas dissected from freeze-dried microtome sections of rat kidney. All three enzymes were essentially confined to the proximal tubule. In normal kidneys, the levels were highest in the proximal convoluted tubule. Glucose-6-phosphatase was 20 times higher in the early part of the convoluted segment than in the late part of the straight segment. With one exception, in acidosis, only phosphoenolpyruvate carboxykinase increased (fourfold in the proximal convoluted segment but much less in the straight portion). In starvation, phosphoenolpyruvate carboxykinase increased about as much as in acidosis in the proximal straight tubule, but not as much in convoluted portions, whereas glucose-6-phosphatase rose modestly in both parts of the proximal tubule and fructose bisphosphatase rose only in the straight tubule, especially the early segment. It is suggested that ammoniagenesis can accompany gluconeogenesis in the proximal convoluted tubule but not in the straight segment."}
{"id": "PMID:211861", "title": "Cholinergic-adrenergic interactions on intestinal ion transport.", "content": "The autonomic control of intestinal electrolyte transport has been investigated in the in vitro, short-circuited rabbit ileum with varying doses of carbachol and with neuroeffector blocking agents. Low-dose carbachol (less than 10(-6) M) and high-dose carbachol (greater than 10(-4) M) had different effects on Na and Cl transport. Low-dose carbachol caused a transient increase in the potential difference and short-circult current, stimulated Cl secretion, and inhibited the residual flux (probably HCO3 secretion). This is a muscarinic response since it is inhibited by atropine (10(-6) M). After an initial increase of the potential difference and short-circuit current, high-dose carbachol reduced these electrical parameters, stimulated Na and Cl absorption, and abolished the residual flux. This is a nicotinic response since it is inhibited by hexamethonium (10(-5) M). This nicotinic response is identical to that reported by others with alpha-adrenergic agents and it was inhibited also by phentolamine (10(-7) M). We propose that high-dose carbachol stimulates nicotinic receptors on postganglionic sympathetic fibers present in our preparations causing a release of catecholamines and a resulting alpha-adrenergic response by the intestinal epithelial cell. The physiological significance of this response in the gut remains to be determined.", "contents": "Cholinergic-adrenergic interactions on intestinal ion transport. The autonomic control of intestinal electrolyte transport has been investigated in the in vitro, short-circuited rabbit ileum with varying doses of carbachol and with neuroeffector blocking agents. Low-dose carbachol (less than 10(-6) M) and high-dose carbachol (greater than 10(-4) M) had different effects on Na and Cl transport. Low-dose carbachol caused a transient increase in the potential difference and short-circult current, stimulated Cl secretion, and inhibited the residual flux (probably HCO3 secretion). This is a muscarinic response since it is inhibited by atropine (10(-6) M). After an initial increase of the potential difference and short-circuit current, high-dose carbachol reduced these electrical parameters, stimulated Na and Cl absorption, and abolished the residual flux. This is a nicotinic response since it is inhibited by hexamethonium (10(-5) M). This nicotinic response is identical to that reported by others with alpha-adrenergic agents and it was inhibited also by phentolamine (10(-7) M). We propose that high-dose carbachol stimulates nicotinic receptors on postganglionic sympathetic fibers present in our preparations causing a release of catecholamines and a resulting alpha-adrenergic response by the intestinal epithelial cell. The physiological significance of this response in the gut remains to be determined."}
{"id": "PMID:211862", "title": "Calcium transport across segments of the rabbit distal nephron in vitro.", "content": "The mechanism of Ca2+ transport by various segments of the distal nephron was studied in vitro using the isolated perfused tubule technique. Calcium absorption in the distal convoluted tubule (DCT) and the granular portion of the cortical collecting duct (CCTg) was significantly enhanced in the presence of parathyroid hormone (PTH), 3 X 10(-2) U/ml. Na+ was absorbed from and K+ was secreted into the lumen of the DCT. The presence of amiloride (5 X 10(-5) M) or furosemide (5 X 10(-5) M) in the perfusate of DCT each caused a partial inhibition of Na+ but not Ca2+ absorption. The foregoing result with Na+ is consistent with the heterogeneous nature of DCT. Net Na+ absorption and K+ secretion also occurred in the CCTg; both processes were completely inhibited by amiloride. Ca2+ absorption occurred in the thick ascending limb of Henle's loop; it was not enhanced by PTH, and the results were consistent with passive movement. No net Ca2+ movement was observed in the nongranular (light) segment of the cortical collecting tubule in the presence or absence of PTH or dibutyryl cyclic adenosine monophosphate.", "contents": "Calcium transport across segments of the rabbit distal nephron in vitro. The mechanism of Ca2+ transport by various segments of the distal nephron was studied in vitro using the isolated perfused tubule technique. Calcium absorption in the distal convoluted tubule (DCT) and the granular portion of the cortical collecting duct (CCTg) was significantly enhanced in the presence of parathyroid hormone (PTH), 3 X 10(-2) U/ml. Na+ was absorbed from and K+ was secreted into the lumen of the DCT. The presence of amiloride (5 X 10(-5) M) or furosemide (5 X 10(-5) M) in the perfusate of DCT each caused a partial inhibition of Na+ but not Ca2+ absorption. The foregoing result with Na+ is consistent with the heterogeneous nature of DCT. Net Na+ absorption and K+ secretion also occurred in the CCTg; both processes were completely inhibited by amiloride. Ca2+ absorption occurred in the thick ascending limb of Henle's loop; it was not enhanced by PTH, and the results were consistent with passive movement. No net Ca2+ movement was observed in the nongranular (light) segment of the cortical collecting tubule in the presence or absence of PTH or dibutyryl cyclic adenosine monophosphate."}
{"id": "PMID:211864", "title": "[A simple modification for the electrochemical oxygen analyzer to improve accuracy during prolonged closed system anaesthesia (author's transl)].", "content": "A simple modification of the condenser used with the electro-chemical oxygen analyzer (Dr\u00e4ger BioMarine OA202 R) consists of filling the distal chamber with hygroscopic silicagel. This prevents condensation of water vapour on the sensor thus allowing the accuracy during prolonged closed system anaesthesia to remain nearly unaffected (fade less than 0.5%/h).", "contents": "[A simple modification for the electrochemical oxygen analyzer to improve accuracy during prolonged closed system anaesthesia (author's transl)]. A simple modification of the condenser used with the electro-chemical oxygen analyzer (Dr\u00e4ger BioMarine OA202 R) consists of filling the distal chamber with hygroscopic silicagel. This prevents condensation of water vapour on the sensor thus allowing the accuracy during prolonged closed system anaesthesia to remain nearly unaffected (fade less than 0.5%/h)."}
{"id": "PMID:211879", "title": "Antagonism of polymyxin B-induced neuromuscular and cardiovascular depression by 4-aminopyridine in the anesthetized cat.", "content": "In an attempt to find a better antidote to polymyxin B-induced neuromuscular blockade, the authors tested 4-aminopyridine, 0.4--1 mg/kg, in ten anesthetized cats. The sciatic--tibialis anterior nerve--muscle preparation was used. The neuromuscular blockade was successfully reversed in all cats. Rapidity of reversal depended on the dose of 4-aminopyridine administered. At 0.6--1 mg/kg, reversal of the twitch response from 20 per cent of control to 80 per cent of control required 2.4 (SE, 0.5) min; to 100 per cent, 14.4 (SE, 3.7) min. An overshoot of the recovery of neuromuscular blockade of 6--10 hours' duration followed the reversal. The mechanical twitch response reached a peak of approximately 140 per cent of control at 2 hours. At a lower dosage, 0.4 mg/kg, two of three cats took more than an hour for complete recovery of the twitch response, and the overshoot was approximately 10 per cent of control. The hypotensive effect of polymyxin B was partially reversed, but the bradycardia was not. It is concluded that 4-aminopyridine is an effective antidote to polymyxin B-induced neuromuscular blockade in the cat.", "contents": "Antagonism of polymyxin B-induced neuromuscular and cardiovascular depression by 4-aminopyridine in the anesthetized cat. In an attempt to find a better antidote to polymyxin B-induced neuromuscular blockade, the authors tested 4-aminopyridine, 0.4--1 mg/kg, in ten anesthetized cats. The sciatic--tibialis anterior nerve--muscle preparation was used. The neuromuscular blockade was successfully reversed in all cats. Rapidity of reversal depended on the dose of 4-aminopyridine administered. At 0.6--1 mg/kg, reversal of the twitch response from 20 per cent of control to 80 per cent of control required 2.4 (SE, 0.5) min; to 100 per cent, 14.4 (SE, 3.7) min. An overshoot of the recovery of neuromuscular blockade of 6--10 hours' duration followed the reversal. The mechanical twitch response reached a peak of approximately 140 per cent of control at 2 hours. At a lower dosage, 0.4 mg/kg, two of three cats took more than an hour for complete recovery of the twitch response, and the overshoot was approximately 10 per cent of control. The hypotensive effect of polymyxin B was partially reversed, but the bradycardia was not. It is concluded that 4-aminopyridine is an effective antidote to polymyxin B-induced neuromuscular blockade in the cat."}
{"id": "PMID:211880", "title": "[Association of angiosarcoma of the liver and hepatoma in vinyl chloride worker].", "content": "This report deals with a 51 years-old man who, for 23 years and 4 months of his working life, had been exposed to vinyl chloride vapors. Autopsy revealed a hepatoma associated with an angiosarcoma of the liver. The case is the first ever to be reported in the medical literature. This case raises doubts about the theory which suggests that the carcinogenic effect of vinyl chloride in man elicit a tumor of vascular nature.", "contents": "[Association of angiosarcoma of the liver and hepatoma in vinyl chloride worker]. This report deals with a 51 years-old man who, for 23 years and 4 months of his working life, had been exposed to vinyl chloride vapors. Autopsy revealed a hepatoma associated with an angiosarcoma of the liver. The case is the first ever to be reported in the medical literature. This case raises doubts about the theory which suggests that the carcinogenic effect of vinyl chloride in man elicit a tumor of vascular nature."}
{"id": "PMID:211881", "title": "Use of the double-isotope, single-injection method for estimating renal function in normal and polybrominated biphenyl-exposed dairy cows.", "content": "A method is described for conducting a rapid and efficient renal function test in dairy cattle. The method, adapted from methods used for man and dogs, utilizes radiolabeled 131I-sodium iodohippurate to determine effective renal plasma flow (ERPF) and 125I-sodium iothalamate to determine glomerular filtration rate (GFR). The mean GFR for adult cattle was determined to be 2.8 +/- 0.4 ml/kg/minute with a biological half-life of 35.5 +/- 1.4 minutes. The mean ERPF was found to be 10.5 +/- 1.9 ml/kg/minute with a half-life of 17.9 +/- 0.6 minutes. These values are comparable with those in man, but are lower than values in dogs. A toxcity study was done with dairy cattle exposed to polybrominated biphenyls (PBB). Efforts were made to determine the amount of time required for kidney lesions to develop and, if possible, to delineate the potential site of action of PBB. Apparently PBB do not affect GFR or ERPF, even though they produce nephrotoxic effects. Potential mechanisms to explain these results are described.", "contents": "Use of the double-isotope, single-injection method for estimating renal function in normal and polybrominated biphenyl-exposed dairy cows. A method is described for conducting a rapid and efficient renal function test in dairy cattle. The method, adapted from methods used for man and dogs, utilizes radiolabeled 131I-sodium iodohippurate to determine effective renal plasma flow (ERPF) and 125I-sodium iothalamate to determine glomerular filtration rate (GFR). The mean GFR for adult cattle was determined to be 2.8 +/- 0.4 ml/kg/minute with a biological half-life of 35.5 +/- 1.4 minutes. The mean ERPF was found to be 10.5 +/- 1.9 ml/kg/minute with a half-life of 17.9 +/- 0.6 minutes. These values are comparable with those in man, but are lower than values in dogs. A toxcity study was done with dairy cattle exposed to polybrominated biphenyls (PBB). Efforts were made to determine the amount of time required for kidney lesions to develop and, if possible, to delineate the potential site of action of PBB. Apparently PBB do not affect GFR or ERPF, even though they produce nephrotoxic effects. Potential mechanisms to explain these results are described."}
{"id": "PMID:211882", "title": "Effect of experimental infection with pseudorabies (Aujeszky's disease) virus on pigs with maternal immunity from vaccinated sows.", "content": "Live-virus and inactivated-virus vaccines were used to immunize sows against pseudorabies (Aujeszky's disease) virus. To test the efficacy of the vaccination, 53 pigs of different ages were taken from the 1st and the 2nd litters of vaccinated sows and placed separately in isolation units. The pigs were challenge exposed with virulent pseudorabies virus and examined for clinical signs, virus excretion, and serologic reaction. The challenge inoculum caused severe nervous or respiratory signs of disease in 12 of the 13 control pigs, with a mortality of 76%. The pigs from the 1st litters of sows vaccinated with the live-virus vaccine did not become sick, whereas 2 of the 9 pigs (22%) from the 2nd litters had clinical signs and died of pseudorabies. All pigs from sows vaccinated with the inactivated-virus vaccine remained healthy. The results of virus isolation from oronasal swabs, combined with the serotest results, indicated that challenge exposure of all except 1 of the pigs resulted in a subclinical infection with the formation of active immunity.", "contents": "Effect of experimental infection with pseudorabies (Aujeszky's disease) virus on pigs with maternal immunity from vaccinated sows. Live-virus and inactivated-virus vaccines were used to immunize sows against pseudorabies (Aujeszky's disease) virus. To test the efficacy of the vaccination, 53 pigs of different ages were taken from the 1st and the 2nd litters of vaccinated sows and placed separately in isolation units. The pigs were challenge exposed with virulent pseudorabies virus and examined for clinical signs, virus excretion, and serologic reaction. The challenge inoculum caused severe nervous or respiratory signs of disease in 12 of the 13 control pigs, with a mortality of 76%. The pigs from the 1st litters of sows vaccinated with the live-virus vaccine did not become sick, whereas 2 of the 9 pigs (22%) from the 2nd litters had clinical signs and died of pseudorabies. All pigs from sows vaccinated with the inactivated-virus vaccine remained healthy. The results of virus isolation from oronasal swabs, combined with the serotest results, indicated that challenge exposure of all except 1 of the pigs resulted in a subclinical infection with the formation of active immunity."}
{"id": "PMID:211884", "title": "Virus isolation and immune responses in susceptible swine exposed with pseudorabies virus (Shope strain).", "content": "Eighteen seronegative swine weighing from 9 to 11 kg were exposed intranasally with the Shope strain of pseudorabies virus (PRV) and were observed for 21 days in an experiment to detect virus shedding and immune responses. All swine had PRV in their nasal passages at 7 days after exposure; they also had precipitating antibodies to PRV as determined by the microimmunodiffusion test (MIDT) and very low levels of virus-neutralizing (VN) antibodies. The PRV was isolated from only 2 swine at postexposure day 14; all swine were MIDT positive, and VN titers ranged from 4 to 128. Virus was not isolated from the swine at 21 days after exposure, but all were MIDT positive; VN titers ranged between 8 and greater than or equal to 256.", "contents": "Virus isolation and immune responses in susceptible swine exposed with pseudorabies virus (Shope strain). Eighteen seronegative swine weighing from 9 to 11 kg were exposed intranasally with the Shope strain of pseudorabies virus (PRV) and were observed for 21 days in an experiment to detect virus shedding and immune responses. All swine had PRV in their nasal passages at 7 days after exposure; they also had precipitating antibodies to PRV as determined by the microimmunodiffusion test (MIDT) and very low levels of virus-neutralizing (VN) antibodies. The PRV was isolated from only 2 swine at postexposure day 14; all swine were MIDT positive, and VN titers ranged from 4 to 128. Virus was not isolated from the swine at 21 days after exposure, but all were MIDT positive; VN titers ranged between 8 and greater than or equal to 256."}
{"id": "PMID:211885", "title": "Experimental infectious bovine rhinotracheitis virus infections of English ferrets (Mustela putorius furo L).", "content": "Intranasal and intraperitoneal exposure of English ferrets (Mustela putorius furo L) to infectious bovine rhinotracheitis virus caused acute and chronic infections of the respiratory tract. The clinical syndrome was characterized by sneezing, coughing, and anorexia from postexposure days (PED) 3 to 7. Mucopurulent exudate was observed in the posterior nares and pharyngeal area of ferrets euthanatized on PED 4 and 8. The virus was readily recovered from the turbinates, respiratory tract epithelium of the pharynx, retropharyngeal lymph nodes, trachea, lungs, and spleen of animals euthanatized on PED 4, but only from the respiratory tract epithelium of the pharynx in ferrets euthanatized on PED 8 and 12. Results of histopathologic studies revealed an acute suppurative pharyngitis in animals euthanatized on PED 4 and 8. Recrudescence of chronic infection could be elicited by daily intraperitoneal injections of 4.0 mg of dexamethasone. However, daily administration of 2.0 mg of dexamethasone intraperitoneally did not cause more severe clinical disease. Results of serologic studies revealed serum antibody profiles comparable with those expected in experimentally exposed cattle.", "contents": "Experimental infectious bovine rhinotracheitis virus infections of English ferrets (Mustela putorius furo L). Intranasal and intraperitoneal exposure of English ferrets (Mustela putorius furo L) to infectious bovine rhinotracheitis virus caused acute and chronic infections of the respiratory tract. The clinical syndrome was characterized by sneezing, coughing, and anorexia from postexposure days (PED) 3 to 7. Mucopurulent exudate was observed in the posterior nares and pharyngeal area of ferrets euthanatized on PED 4 and 8. The virus was readily recovered from the turbinates, respiratory tract epithelium of the pharynx, retropharyngeal lymph nodes, trachea, lungs, and spleen of animals euthanatized on PED 4, but only from the respiratory tract epithelium of the pharynx in ferrets euthanatized on PED 8 and 12. Results of histopathologic studies revealed an acute suppurative pharyngitis in animals euthanatized on PED 4 and 8. Recrudescence of chronic infection could be elicited by daily intraperitoneal injections of 4.0 mg of dexamethasone. However, daily administration of 2.0 mg of dexamethasone intraperitoneally did not cause more severe clinical disease. Results of serologic studies revealed serum antibody profiles comparable with those expected in experimentally exposed cattle."}
{"id": "PMID:211886", "title": "Neural changes in recurrent infection of infectious bovine rhinotracheitis virus in calves treated with dexamethasone.", "content": "Recurrent infection by infectious bovine rhinotracheitis (IBR) virus was induced in calves by dexamethasone (DM) treatment (given 5 days) at 5 months after primary infection. The virus appeared in nasal secretions of the calves on the 4th day after initiation of DM treatment and continued until the 9th day. The calves were killed on the 1st, 3rd, 4th, 5th, 6th, 7th, 8th, 10th, and 11th days after DM treatment was started for examination by histopathologic and immunofluorescent antibody techniques. The most significant neural change was trigeminal ganglionitis with neuronophagia, which was observed from the 3rd to the 11th day. Significantly, the extent of changes in the trigeminal ganglion and medulla oblongata corresponded to the amount of DM treatment administered. The IBR virus antigen was first observed in the trigeminal ganglion cells, and thereafter, it was detected in the Schwann cells, satellite cells, neuroglia cells, and nasal mucosa until the 10th day. These observations indicate that the IBR virus is capalbe of producing a persistent infection in the trigeminal ganglion and that trigeminal ganglionitis may be a characteristic lesion for inducing the reactivation of lagent IBR virus.", "contents": "Neural changes in recurrent infection of infectious bovine rhinotracheitis virus in calves treated with dexamethasone. Recurrent infection by infectious bovine rhinotracheitis (IBR) virus was induced in calves by dexamethasone (DM) treatment (given 5 days) at 5 months after primary infection. The virus appeared in nasal secretions of the calves on the 4th day after initiation of DM treatment and continued until the 9th day. The calves were killed on the 1st, 3rd, 4th, 5th, 6th, 7th, 8th, 10th, and 11th days after DM treatment was started for examination by histopathologic and immunofluorescent antibody techniques. The most significant neural change was trigeminal ganglionitis with neuronophagia, which was observed from the 3rd to the 11th day. Significantly, the extent of changes in the trigeminal ganglion and medulla oblongata corresponded to the amount of DM treatment administered. The IBR virus antigen was first observed in the trigeminal ganglion cells, and thereafter, it was detected in the Schwann cells, satellite cells, neuroglia cells, and nasal mucosa until the 10th day. These observations indicate that the IBR virus is capalbe of producing a persistent infection in the trigeminal ganglion and that trigeminal ganglionitis may be a characteristic lesion for inducing the reactivation of lagent IBR virus."}
{"id": "PMID:211887", "title": "Immune responses in swine given lipid-conjugated pseudorabies viral antigens.", "content": "The immune response was compared in pigs given inactivated pseudorabies virus (PRV) antigens (with or without adjuvant) or PRV antigens covalently conjugated with a fatty acid (lauric acid) to enhance delayed-type hypersensitivity. The pigs were given 2 inoculations, 14 days apart, and were challenge exposed 28 days after the 1st inoculation. Pibs inoculated with PRV antigens, with or without adjuvant, had significant virus-neutralizing (VN) antibodies before challenge exposure, but the pigs inoculated with lipid-conjugated PRV antigens had no detectable VN antibodies, with the exception of 1 pig. All inoculated pigs were positive by the microimmunodiffusion test at postinoculation day 14 and remained positive throughout the experiment. The inoculated pigs had delayed-type hypersensitivity reactions when skin tested a postinoculation day 25; the pigs inoculated with lipid-conjugated PRV antigens had a more pronounced reaction. Inoculated pigs had mild respiratory signs on the 3rd through the 6th days after challange exposure, with no observable difference in severity between the inoculated groups. The control pigs had acute signs of PRV, and 3 or 4 pigs died 5 to 8 days after challenge exposure. The average VN titers of the different inoculated groups of pigs were nearly equal 2 weeks after challenge exposure. Results indicated that both humoral antibodies and cell-mediated immunity have a role in PRV infections in swine.", "contents": "Immune responses in swine given lipid-conjugated pseudorabies viral antigens. The immune response was compared in pigs given inactivated pseudorabies virus (PRV) antigens (with or without adjuvant) or PRV antigens covalently conjugated with a fatty acid (lauric acid) to enhance delayed-type hypersensitivity. The pigs were given 2 inoculations, 14 days apart, and were challenge exposed 28 days after the 1st inoculation. Pibs inoculated with PRV antigens, with or without adjuvant, had significant virus-neutralizing (VN) antibodies before challenge exposure, but the pigs inoculated with lipid-conjugated PRV antigens had no detectable VN antibodies, with the exception of 1 pig. All inoculated pigs were positive by the microimmunodiffusion test at postinoculation day 14 and remained positive throughout the experiment. The inoculated pigs had delayed-type hypersensitivity reactions when skin tested a postinoculation day 25; the pigs inoculated with lipid-conjugated PRV antigens had a more pronounced reaction. Inoculated pigs had mild respiratory signs on the 3rd through the 6th days after challange exposure, with no observable difference in severity between the inoculated groups. The control pigs had acute signs of PRV, and 3 or 4 pigs died 5 to 8 days after challenge exposure. The average VN titers of the different inoculated groups of pigs were nearly equal 2 weeks after challenge exposure. Results indicated that both humoral antibodies and cell-mediated immunity have a role in PRV infections in swine."}
{"id": "PMID:211888", "title": "Colostral IgA, IgG, and IgM-IgA fractions as fluorescent antibody for the detection of the coronavirus of transmissible gastroenteritis.", "content": "Colostrum from sows and gilts inoculated with virulent transmissible gastroenteritis virus was fractionated into the 3 major immunoglobulin classes, IgA, IgG, and IgM-IgA fractions, by chromatographic and gel-filtration procedures. Each fraction was assayed for purity with rabbit anti-porcine serum and rabbit monospecific anti-porcine IgG, anti-porcine IgA, and anti-porcine IgM. These analyses showed that the IgG and IgA fractions were pure. The IgM fraction contained some IgA in the polymeric form and was designated the IgM-IgA fraction. Each Ig was assayed for virus-neutralizing activity on swine testes cells by the plaque-reduction method before and after conjugation with fluorescein isothiocyanate. On the basis of activity per milligram of protein, the virus-neutralizing titers were 1:641, 1:44, and 1:6.8 for the IgA, IgG, and IgM-IgA fractions respectively; the fluorescent antibody titers were 1:31.3, 1:0.1, and 1:15.6, respectively, for the same Ig.", "contents": "Colostral IgA, IgG, and IgM-IgA fractions as fluorescent antibody for the detection of the coronavirus of transmissible gastroenteritis. Colostrum from sows and gilts inoculated with virulent transmissible gastroenteritis virus was fractionated into the 3 major immunoglobulin classes, IgA, IgG, and IgM-IgA fractions, by chromatographic and gel-filtration procedures. Each fraction was assayed for purity with rabbit anti-porcine serum and rabbit monospecific anti-porcine IgG, anti-porcine IgA, and anti-porcine IgM. These analyses showed that the IgG and IgA fractions were pure. The IgM fraction contained some IgA in the polymeric form and was designated the IgM-IgA fraction. Each Ig was assayed for virus-neutralizing activity on swine testes cells by the plaque-reduction method before and after conjugation with fluorescein isothiocyanate. On the basis of activity per milligram of protein, the virus-neutralizing titers were 1:641, 1:44, and 1:6.8 for the IgA, IgG, and IgM-IgA fractions respectively; the fluorescent antibody titers were 1:31.3, 1:0.1, and 1:15.6, respectively, for the same Ig."}
{"id": "PMID:211889", "title": "Secretory antibodies against turkey coronaviral enteritis.", "content": "Studies on local immunity to transmissible coronaviral enteritis of turkeys (bluecomb) was made. Intestinal secretions and bile from affected birds contained secretory immunoglobulins against coronaviral antigen throughout the 6 months' duration of the experiment. Attempts to purify and to characterize the globulins in intestinal secretions and bile of the affected birds were made, using the techniques of gel filtration, DEAE chromatography, and immunoelectrophoresis. Class-specific anti-turkey IgA antiserum in the agar gel precipitin test further established the presence of IgA in the intestinal secretions and bile.", "contents": "Secretory antibodies against turkey coronaviral enteritis. Studies on local immunity to transmissible coronaviral enteritis of turkeys (bluecomb) was made. Intestinal secretions and bile from affected birds contained secretory immunoglobulins against coronaviral antigen throughout the 6 months' duration of the experiment. Attempts to purify and to characterize the globulins in intestinal secretions and bile of the affected birds were made, using the techniques of gel filtration, DEAE chromatography, and immunoelectrophoresis. Class-specific anti-turkey IgA antiserum in the agar gel precipitin test further established the presence of IgA in the intestinal secretions and bile."}
{"id": "PMID:211890", "title": "Mortality after long exposure to cummingtonite-grunerite.", "content": "Ore containing cummingtonite-grunerite has been mined to extract gold since 1876 in Lead, South Dakota. Each of the 1,321 men who were recorded as having worked 21 years or more with the Homestake Mine was allocated to one of 5 dust-exposure categories on the basis of work history and available information on environmental conditions. All except 9 men were traced to the end of 1973, when 652 were still living; the cause of death was ascertained for 657 of the 660 men who had died. Deaths from cerebrovascular accidents and malignant disease were close to the numbers expected and from accidents and other causes were fewer than expected, but in each of the 3 diagnostic groups--pneumoconiosis (mainly silicosis), tuberculosis, and heart disease--there were more than 30 excess deaths. A clear dust-exposure relationship was found for pneumoconiosis and respiratory tuberculosis--with relative risks for the 2 groups with greatest exposure to dust as compared to the 2 with least exposure, of 19.9 and 16.0, respectively, but there was no convincing evidence of an increase in respiratory cancer.", "contents": "Mortality after long exposure to cummingtonite-grunerite. Ore containing cummingtonite-grunerite has been mined to extract gold since 1876 in Lead, South Dakota. Each of the 1,321 men who were recorded as having worked 21 years or more with the Homestake Mine was allocated to one of 5 dust-exposure categories on the basis of work history and available information on environmental conditions. All except 9 men were traced to the end of 1973, when 652 were still living; the cause of death was ascertained for 657 of the 660 men who had died. Deaths from cerebrovascular accidents and malignant disease were close to the numbers expected and from accidents and other causes were fewer than expected, but in each of the 3 diagnostic groups--pneumoconiosis (mainly silicosis), tuberculosis, and heart disease--there were more than 30 excess deaths. A clear dust-exposure relationship was found for pneumoconiosis and respiratory tuberculosis--with relative risks for the 2 groups with greatest exposure to dust as compared to the 2 with least exposure, of 19.9 and 16.0, respectively, but there was no convincing evidence of an increase in respiratory cancer."}
{"id": "PMID:211891", "title": "[Kinetics of production of collagenase, esterase and elastase by human and soil strains of \"Entomophthora coronata\" (author's transl)].", "content": "A comparative study was made of the production of extracellular proteolytic enzymes, which were originated from two different strains, one pathogenic and one saprophytic, of E. coronata in stable culture at 30 degrees C. Quantitative differences were found: the maximal activity of the three enzymes (collagenase, esterase, elastase) produced by the strain isolated from soil was always lower than that observed with the human strain.", "contents": "[Kinetics of production of collagenase, esterase and elastase by human and soil strains of \"Entomophthora coronata\" (author's transl)]. A comparative study was made of the production of extracellular proteolytic enzymes, which were originated from two different strains, one pathogenic and one saprophytic, of E. coronata in stable culture at 30 degrees C. Quantitative differences were found: the maximal activity of the three enzymes (collagenase, esterase, elastase) produced by the strain isolated from soil was always lower than that observed with the human strain."}
{"id": "PMID:211892", "title": "[Assay of human anti-exoproteins to group A streptococci by microhaemagglutination: correlation with anti-streptolysin O and various anti-enzymes (author's transl)].", "content": "A microhaemagglutination test in disposable U plates has been devised for rapid, quantitative evaluation in antistreptococcal antibodies in human sera. Fresh or freeze-dried glutaraldehyde-treated sheep erythrocytes sensitized with over fifteen extracellular proteins released by group A Streptococcus pyogenes including streptolysin O, deoxyribonucleases, hyaluronatelyase, streptokinase and nicotinamide dinucleotide glycohydrolase were used. Haemagglutination and anti-streptolysin O (ASLO) titers were determined in parallel on 434 serum specimens from 123 healthy subjects (\"controls\") and 311 patients with a history of supposed or evident streptococcal infection. The titration of the four above-mentioned anti-enzyme antibodies has also been made on about 100 sera from both groups. Haemagglutination titre (HT) was less than 800 in control sera. By contrast it was greater than 800 up to 12 800 in patients specimens. Very good correlation was found between HT on the one hand and ASLO or anti-SK, anti-HA and anti-NADase antibodies on the other hand. HT and anti-DNase B antibodies were less correlated. Haemagglutination titres appear to rise earlier than serological titres of conventional streptococcal antibodies. The haemagglutination test described may be particularly helpful as a rapid serologic indicator of streptococcal infections and more reliable than the titration of ASLO alone, or of any one of anti-enzyme antibodies.", "contents": "[Assay of human anti-exoproteins to group A streptococci by microhaemagglutination: correlation with anti-streptolysin O and various anti-enzymes (author's transl)]. A microhaemagglutination test in disposable U plates has been devised for rapid, quantitative evaluation in antistreptococcal antibodies in human sera. Fresh or freeze-dried glutaraldehyde-treated sheep erythrocytes sensitized with over fifteen extracellular proteins released by group A Streptococcus pyogenes including streptolysin O, deoxyribonucleases, hyaluronatelyase, streptokinase and nicotinamide dinucleotide glycohydrolase were used. Haemagglutination and anti-streptolysin O (ASLO) titers were determined in parallel on 434 serum specimens from 123 healthy subjects (\"controls\") and 311 patients with a history of supposed or evident streptococcal infection. The titration of the four above-mentioned anti-enzyme antibodies has also been made on about 100 sera from both groups. Haemagglutination titre (HT) was less than 800 in control sera. By contrast it was greater than 800 up to 12 800 in patients specimens. Very good correlation was found between HT on the one hand and ASLO or anti-SK, anti-HA and anti-NADase antibodies on the other hand. HT and anti-DNase B antibodies were less correlated. Haemagglutination titres appear to rise earlier than serological titres of conventional streptococcal antibodies. The haemagglutination test described may be particularly helpful as a rapid serologic indicator of streptococcal infections and more reliable than the titration of ASLO alone, or of any one of anti-enzyme antibodies."}
{"id": "PMID:211896", "title": "The cells of origin of ACTH in man.", "content": "The evidence from ACTH-producing tumors, from the morphologic effects of excess glucorticoids on the hypophysis, and from immunocytochemistry all points to the predominant \"basophils\" of the human anterior lobe, the intensely PAS-possitive beta(R) cells, as the source of ACTH. Similar cells often also occur, sometimes in large numbers, in the pars nervosa. beta(R) cells can be immunostained with antibodies against alphaMSH and betaMSH, but it is likely that they actually contain the precursor molecule(s) of betaMSH, betaLPH (and may be gammaLPH). Once this is satisfactorily documented, the functional term corticolipotrops should replace the provisional name beta(R) cells. Electron microscopically, these cells contain randomly arranged granules with a maximum diameter of 300-500 nm, and occasionally small amounts of filamentous material, which increases dramatically in response to excess glucocorticoids. In the beta (R) cells of adults, a single set of granules stains for ACTH and with antibodies to betaMSH. In fetal life, ACTH cells appear early and material reactive with anti-betaMSH accumulates in them (and possibly also in cells not containing ACTH) only later. The posterior lobe beta(R) cells can be immunostained with both anti-betaMSH and antibodies against the COOH-terminal portion of ACTH, but the presence of bioactive ACTH in them remains to be shown.", "contents": "The cells of origin of ACTH in man. The evidence from ACTH-producing tumors, from the morphologic effects of excess glucorticoids on the hypophysis, and from immunocytochemistry all points to the predominant \"basophils\" of the human anterior lobe, the intensely PAS-possitive beta(R) cells, as the source of ACTH. Similar cells often also occur, sometimes in large numbers, in the pars nervosa. beta(R) cells can be immunostained with antibodies against alphaMSH and betaMSH, but it is likely that they actually contain the precursor molecule(s) of betaMSH, betaLPH (and may be gammaLPH). Once this is satisfactorily documented, the functional term corticolipotrops should replace the provisional name beta(R) cells. Electron microscopically, these cells contain randomly arranged granules with a maximum diameter of 300-500 nm, and occasionally small amounts of filamentous material, which increases dramatically in response to excess glucocorticoids. In the beta (R) cells of adults, a single set of granules stains for ACTH and with antibodies to betaMSH. In fetal life, ACTH cells appear early and material reactive with anti-betaMSH accumulates in them (and possibly also in cells not containing ACTH) only later. The posterior lobe beta(R) cells can be immunostained with both anti-betaMSH and antibodies against the COOH-terminal portion of ACTH, but the presence of bioactive ACTH in them remains to be shown."}
{"id": "PMID:211893", "title": "[Rapid virus diagnosis by electrosyneresis (author's transl)].", "content": "Electrosyneresis (counter-current immunoelectrophoresis) detected the presence of 7 coxsackieviruses and 1 poliovirus in 70 specimens of stools. Identical results were obtained by inoculation of mice and tissue cultures. First screening of specimens was undertaken with a human \"standard\" gammaglobulin; only specimens precipitating with this reagent contained viral antigens. Hence, especially in children, all negative stools could be excluded from subsequent tests with antiserum pools and monospecific antisera. In our experience, electrosyneresis is a specific method: every type of coxsackievirus and poliovirus types react only with the corresponding monospecific antisera. Electrosyneresis appears to be a sensitive procedure: viral antigens corresponding to 10(4) TCID50/ml can be dtected.", "contents": "[Rapid virus diagnosis by electrosyneresis (author's transl)]. Electrosyneresis (counter-current immunoelectrophoresis) detected the presence of 7 coxsackieviruses and 1 poliovirus in 70 specimens of stools. Identical results were obtained by inoculation of mice and tissue cultures. First screening of specimens was undertaken with a human \"standard\" gammaglobulin; only specimens precipitating with this reagent contained viral antigens. Hence, especially in children, all negative stools could be excluded from subsequent tests with antiserum pools and monospecific antisera. In our experience, electrosyneresis is a specific method: every type of coxsackievirus and poliovirus types react only with the corresponding monospecific antisera. Electrosyneresis appears to be a sensitive procedure: viral antigens corresponding to 10(4) TCID50/ml can be dtected."}
{"id": "PMID:211894", "title": "[Unmasking effect of trypsin on Sendai virions obtained in KB cell cultures (author's transl)].", "content": "The infectivity of virus grown in KB cell cultures can be directly activated by trypsin. Thus the fit conditions for seeding are effected from subculture to subculture if the cell inoculum is pretreated by trypsin.", "contents": "[Unmasking effect of trypsin on Sendai virions obtained in KB cell cultures (author's transl)]. The infectivity of virus grown in KB cell cultures can be directly activated by trypsin. Thus the fit conditions for seeding are effected from subculture to subculture if the cell inoculum is pretreated by trypsin."}
{"id": "PMID:211912", "title": "Assays and dynamics of corticotropin-releasing factor activity in rat hypothalamus.", "content": "Features of several assays for corticotropin-releasing factor (CRF) were compared, with reference to sensitivity, precision, specificity and convenience. In general, in vivo assays are less specific, whereas in vitro assays with isolated pituitary cells appear to suffer from vulnerability. Promising approaches for overcoming this difficulty are appearing: one is the cell culture technique and the other is the perfusion of pituitary cell column. However, the findings with vasopressin are again discordant. So far, the in vivo-in vitro assay system appears to be the most satisfactory. In this connection, special emphasis was laid on the CRF assay by out intrapituitary injection technique through the parapharyngeal approach, which has features of both in vivo and in vitro systems. The drawbacks with this assay are its complexity and relatively lower precision. Problems of the use of dexamethasone are discussed from a viewpoint of possible multistage feedback inhibition, as postulated by Yates et al. Several findings on the CRF dynamics were mentioned, in order to exemplify the findings obtained with our assay: it was shown that the two-peaked changes of CRF after ether-laparotomy stress in adult rats were composed of heterogeneous components, as revealed by differential effect of cycloheximide. Pretreatment with cycloheximide similarly abolished the delayed CRF peak that was observed in 2-day-old neonatal rats under stress. These findings suggest an operation of a biochemical denominator in common with both cases.", "contents": "Assays and dynamics of corticotropin-releasing factor activity in rat hypothalamus. Features of several assays for corticotropin-releasing factor (CRF) were compared, with reference to sensitivity, precision, specificity and convenience. In general, in vivo assays are less specific, whereas in vitro assays with isolated pituitary cells appear to suffer from vulnerability. Promising approaches for overcoming this difficulty are appearing: one is the cell culture technique and the other is the perfusion of pituitary cell column. However, the findings with vasopressin are again discordant. So far, the in vivo-in vitro assay system appears to be the most satisfactory. In this connection, special emphasis was laid on the CRF assay by out intrapituitary injection technique through the parapharyngeal approach, which has features of both in vivo and in vitro systems. The drawbacks with this assay are its complexity and relatively lower precision. Problems of the use of dexamethasone are discussed from a viewpoint of possible multistage feedback inhibition, as postulated by Yates et al. Several findings on the CRF dynamics were mentioned, in order to exemplify the findings obtained with our assay: it was shown that the two-peaked changes of CRF after ether-laparotomy stress in adult rats were composed of heterogeneous components, as revealed by differential effect of cycloheximide. Pretreatment with cycloheximide similarly abolished the delayed CRF peak that was observed in 2-day-old neonatal rats under stress. These findings suggest an operation of a biochemical denominator in common with both cases."}
{"id": "PMID:211914", "title": "Neural control of ACTH release in response to hemorrhage.", "content": "A three dimensional reconstruction of the central neural pathways that appear to mediate release of ACTH in response to hemodynamic change is illustrated in Figure 11. Fibers from receptors in the right atrium and the carotid arteries project to the lateral solitary nucleus and then to the medial and the lateral nucleus intercalatus. A pathway containing projections from these nuclei then converges dominantly in the locus subcoeruleus and locus coeruleus. Multiple pathways then diverge, to travel in part directly to the hypothalamus through dorsal pathways. One pathway inhibits and another facilitates the release of ACTH. Multiple pathways also diverge, to travel in part medially, and then to the hypothalamus through ventral pathways. Again, one pathway inhibits and another facilitates the release of ACTH. The dorsal and ventral inhibitory pathways appear to converge in a region extending from just caudal and ventral to the paraventicular nucleus to the posterior hypothalamic area. Thus, after the coalescences of the various pontine-hypothalamic pathways, three principal pathways remain. These include a posterior inhibitor path, an anterodorsal facilitatory path that terminates in the paraventricular nucleus and that may be mediated through release of vasopressin, and an anteroventral facilitatory path that terminates in the suprachiasmatic and ventromedial nuclei and that is probably mediated through release of corticotropin-releasing hormone. The mode of integration of these pathways has not been defined. The pathways described herein are oligosynaptic: a signal may travel from atrium to hypothalamus over three to seven neurons. The combination of control of input hemodynamic signals and of measurement of ACTH permits quantitation of both sensory and motor events, that inevitably must be embedded in the neuronal pathways described here. The analysis of the input-output relations and their correlation with internal neural events must form the basis of a description of the physiology of the physiology of the system whose central neural anatomy has been defined in part by these studies.", "contents": "Neural control of ACTH release in response to hemorrhage. A three dimensional reconstruction of the central neural pathways that appear to mediate release of ACTH in response to hemodynamic change is illustrated in Figure 11. Fibers from receptors in the right atrium and the carotid arteries project to the lateral solitary nucleus and then to the medial and the lateral nucleus intercalatus. A pathway containing projections from these nuclei then converges dominantly in the locus subcoeruleus and locus coeruleus. Multiple pathways then diverge, to travel in part directly to the hypothalamus through dorsal pathways. One pathway inhibits and another facilitates the release of ACTH. Multiple pathways also diverge, to travel in part medially, and then to the hypothalamus through ventral pathways. Again, one pathway inhibits and another facilitates the release of ACTH. The dorsal and ventral inhibitory pathways appear to converge in a region extending from just caudal and ventral to the paraventicular nucleus to the posterior hypothalamic area. Thus, after the coalescences of the various pontine-hypothalamic pathways, three principal pathways remain. These include a posterior inhibitor path, an anterodorsal facilitatory path that terminates in the paraventricular nucleus and that may be mediated through release of vasopressin, and an anteroventral facilitatory path that terminates in the suprachiasmatic and ventromedial nuclei and that is probably mediated through release of corticotropin-releasing hormone. The mode of integration of these pathways has not been defined. The pathways described herein are oligosynaptic: a signal may travel from atrium to hypothalamus over three to seven neurons. The combination of control of input hemodynamic signals and of measurement of ACTH permits quantitation of both sensory and motor events, that inevitably must be embedded in the neuronal pathways described here. The analysis of the input-output relations and their correlation with internal neural events must form the basis of a description of the physiology of the physiology of the system whose central neural anatomy has been defined in part by these studies."}
{"id": "PMID:211916", "title": "Plasma ACTH levels in stressed and nonstressed adrenalectomized rats.", "content": "Following adrenalectomy there is a triphasic response of ACTH secretion characterized by an initial high rise immediately following the adrenalectomy, secondary to the stress of the procedure. This is followed by a fall to resting ACTH secretion until a steady state is reached 1 to 2 weeks following adrenalectomy at levels about 10 times normal. The ability to respond to stress with increased ACTH secretion is not lost at any time following adrenalectomy.", "contents": "Plasma ACTH levels in stressed and nonstressed adrenalectomized rats. Following adrenalectomy there is a triphasic response of ACTH secretion characterized by an initial high rise immediately following the adrenalectomy, secondary to the stress of the procedure. This is followed by a fall to resting ACTH secretion until a steady state is reached 1 to 2 weeks following adrenalectomy at levels about 10 times normal. The ability to respond to stress with increased ACTH secretion is not lost at any time following adrenalectomy."}
{"id": "PMID:211922", "title": "The nutritional epidemiology of cardiovascular disease.", "content": "A basic review of the extensive literature focusing on the major risk factors of atherosclerotic coronary heart disease and stroke, i.e., elevation of blood lipids related to diet, blood pressure elevation, and genetic factors using the traditional epidemiological model of interaction between host, agent, and environment, has strongly supported the concept that diet and particularly saturated fat and/or cholesterol are significant contributors to the elevation of blood lipids, especially cholesterol, and contribute importantly to the premature development and mortality of atherosclerotic coronary heart disease. Certainly genetics exert an important impact on this process. To date it remains unclear whether or not major changes in the dietary pattern of huge population groups can be practically effected. The minor dietary modifications so far studied in the average atherosclerosis-prone population cannot be anticipated to make a major dent in the epidemic proportions of atherosclerotic coronary heart disease. It is quite clear that prospective preventive medicine must be implemented at a very early age in the pediatric age group, in which atherosclerosis is now recognized by many as the number one pediatric problem. Tremendous biochemical advances have provided new insights in knowledge regarding the transport of blood lipids, particularly cholesterol, and the regulatory mechanisms at the cellular level for cholesterol under normal circumstances and in the genetic influenced hyperlipidemias (TABLE 4). A bright future lies ahead for the reduction of the epidemic of atherosclerosis which could be greatly enhanced by a greater personal responsibility for health care and a much more careful and prudent diet selection and exercise managment.", "contents": "The nutritional epidemiology of cardiovascular disease. A basic review of the extensive literature focusing on the major risk factors of atherosclerotic coronary heart disease and stroke, i.e., elevation of blood lipids related to diet, blood pressure elevation, and genetic factors using the traditional epidemiological model of interaction between host, agent, and environment, has strongly supported the concept that diet and particularly saturated fat and/or cholesterol are significant contributors to the elevation of blood lipids, especially cholesterol, and contribute importantly to the premature development and mortality of atherosclerotic coronary heart disease. Certainly genetics exert an important impact on this process. To date it remains unclear whether or not major changes in the dietary pattern of huge population groups can be practically effected. The minor dietary modifications so far studied in the average atherosclerosis-prone population cannot be anticipated to make a major dent in the epidemic proportions of atherosclerotic coronary heart disease. It is quite clear that prospective preventive medicine must be implemented at a very early age in the pediatric age group, in which atherosclerosis is now recognized by many as the number one pediatric problem. Tremendous biochemical advances have provided new insights in knowledge regarding the transport of blood lipids, particularly cholesterol, and the regulatory mechanisms at the cellular level for cholesterol under normal circumstances and in the genetic influenced hyperlipidemias (TABLE 4). A bright future lies ahead for the reduction of the epidemic of atherosclerosis which could be greatly enhanced by a greater personal responsibility for health care and a much more careful and prudent diet selection and exercise managment."}
{"id": "PMID:211928", "title": "Adult cytomegalic inclusion retinitis.", "content": "Two cases of adult cytomegalic inclusion retinitis are described in renal transplant patients. The areas of initial involvement by the retinitis were left atrophic and demarcated from normal retina by a hypopigmented area in the retina. Both cases were complicated by the development of a secondary glaucoma with open angles. The glaucoma in each patient was successfully managed by carbonic anhydrase inhibitors, epinephrine drops, and cycloplegias. One patient still retains normal visual acuity in the eye which had active retinitis.", "contents": "Adult cytomegalic inclusion retinitis. Two cases of adult cytomegalic inclusion retinitis are described in renal transplant patients. The areas of initial involvement by the retinitis were left atrophic and demarcated from normal retina by a hypopigmented area in the retina. Both cases were complicated by the development of a secondary glaucoma with open angles. The glaucoma in each patient was successfully managed by carbonic anhydrase inhibitors, epinephrine drops, and cycloplegias. One patient still retains normal visual acuity in the eye which had active retinitis."}
{"id": "PMID:211929", "title": "Ultrastructure and biochemistry of sympathetic ganglia in idiopathic orthostatic hypotension.", "content": "The role of transsynaptic dysfunction in the pathogenesis of idiopathic orthostatic hypotension (IOH, or idiopathic autonomic insufficiency) was examined microscopically and biochemically in autopsy specimens. Light microscopy of the sympathetic ganglia showed abnormalities in all 4 IOH patients, including focal phagocytosis of neurons, increased numbers of satellite cells, and perivascular lymphocytic infiltrates. Electron microscopy revealed proliferation and hypertrophy of satellite cells and abnormalities in the unmyelinated axons. In contrast, the spinal cord intermediolateral columns, containing the presynaptic neurons, were unremarkable in 1 patient, exhibited only mild gliosis in another, and showed neuron loss and fibrillary gliosis in 2 patients. Postsynaptic dopamine-beta-hydroxylase (DBH) activity was decreased at least fourfold (p less than 0.02) in sympathetic ganglia of patients with IOH, while tyrosine hydroxylase (T-OH) was normal. Ganglion choline acetyltransferase (ChAc) activity, an index of presynaptic function and integrity, was normal in the IOH group. A number of our observations suggest that presynaptic disease is not an absolute requirement for adrenergic abnormalities in IOH. The intermediolateral columns of the spinal cord were histologically normal in 2 of the patients with IOH, and ultrastructural abnormalities in sympathetic ganglia were consistent with primary adrenergic degeneration. In addition, presynaptic ChAc activity was normal in IOH ganglia, whereas postsynaptic DBH activity was depressed. Finally, postsynaptic T-OH activity, which is regulated by transsynaptic mechanisms, was normal in IOH ganglia.", "contents": "Ultrastructure and biochemistry of sympathetic ganglia in idiopathic orthostatic hypotension. The role of transsynaptic dysfunction in the pathogenesis of idiopathic orthostatic hypotension (IOH, or idiopathic autonomic insufficiency) was examined microscopically and biochemically in autopsy specimens. Light microscopy of the sympathetic ganglia showed abnormalities in all 4 IOH patients, including focal phagocytosis of neurons, increased numbers of satellite cells, and perivascular lymphocytic infiltrates. Electron microscopy revealed proliferation and hypertrophy of satellite cells and abnormalities in the unmyelinated axons. In contrast, the spinal cord intermediolateral columns, containing the presynaptic neurons, were unremarkable in 1 patient, exhibited only mild gliosis in another, and showed neuron loss and fibrillary gliosis in 2 patients. Postsynaptic dopamine-beta-hydroxylase (DBH) activity was decreased at least fourfold (p less than 0.02) in sympathetic ganglia of patients with IOH, while tyrosine hydroxylase (T-OH) was normal. Ganglion choline acetyltransferase (ChAc) activity, an index of presynaptic function and integrity, was normal in the IOH group. A number of our observations suggest that presynaptic disease is not an absolute requirement for adrenergic abnormalities in IOH. The intermediolateral columns of the spinal cord were histologically normal in 2 of the patients with IOH, and ultrastructural abnormalities in sympathetic ganglia were consistent with primary adrenergic degeneration. In addition, presynaptic ChAc activity was normal in IOH ganglia, whereas postsynaptic DBH activity was depressed. Finally, postsynaptic T-OH activity, which is regulated by transsynaptic mechanisms, was normal in IOH ganglia."}
{"id": "PMID:211930", "title": "Increased sodium plus potassium adenosine triphosphatase activity in erythrocyte membranes in Huntington's disease.", "content": "Dopa-decarboxylase, acetylcholinesterase, sodium plus potassium stimulated adenosine triphosphatase (Na+ + K+-ATPase), and membrane-bound protein kinase were compared in the erythrocytes of patients with Huntington's disease and normal controls. All these enzymes also exist in the basal ganglia. The Na+ +K+-ATPase level was elevated (p less than 0.05) in Huntington's disease, while no significant changes were observed in the other enzymes. This finding is consistent with the concept that Huntington's disease is associated with a general membrane abnormality.", "contents": "Increased sodium plus potassium adenosine triphosphatase activity in erythrocyte membranes in Huntington's disease. Dopa-decarboxylase, acetylcholinesterase, sodium plus potassium stimulated adenosine triphosphatase (Na+ + K+-ATPase), and membrane-bound protein kinase were compared in the erythrocytes of patients with Huntington's disease and normal controls. All these enzymes also exist in the basal ganglia. The Na+ +K+-ATPase level was elevated (p less than 0.05) in Huntington's disease, while no significant changes were observed in the other enzymes. This finding is consistent with the concept that Huntington's disease is associated with a general membrane abnormality."}
{"id": "PMID:211931", "title": "Acetylcholine release in diaphragm of rats with chronic experimental autoimmune myasthenia gravis.", "content": "Recent evidence indicates that in chronic experimental autoimmune myasthenia gravis (EAMG) and in human myasthenia gravis, the defect of neuromuscular transmission results from immune-mediated destruction of post-synaptic membrane at the neuromuscular junction, with a reduction in the density of acetylcholine (ACh) receptors and decreased sensitivity to ACh released by nerve impulses. In the present study, the amount of ACh released by nerve impulse in rats with chronic EAMG and control rats of the same age, weight, and sex was compared. Phrenic nerve-hemidiaphragm preparations were stimulated in vitro, and the amount of ACh released was measured by bioassay. Despite a marked reduction in the amplitude of miniature end-plate potentials in chronic EAMG, ACh output at rest and during stimulation was not different from that of control rats. These data support the concept that the defect of neuromuscular transmission is due to a reduction of postsynaptic sensitivity to ACh.", "contents": "Acetylcholine release in diaphragm of rats with chronic experimental autoimmune myasthenia gravis. Recent evidence indicates that in chronic experimental autoimmune myasthenia gravis (EAMG) and in human myasthenia gravis, the defect of neuromuscular transmission results from immune-mediated destruction of post-synaptic membrane at the neuromuscular junction, with a reduction in the density of acetylcholine (ACh) receptors and decreased sensitivity to ACh released by nerve impulses. In the present study, the amount of ACh released by nerve impulse in rats with chronic EAMG and control rats of the same age, weight, and sex was compared. Phrenic nerve-hemidiaphragm preparations were stimulated in vitro, and the amount of ACh released was measured by bioassay. Despite a marked reduction in the amplitude of miniature end-plate potentials in chronic EAMG, ACh output at rest and during stimulation was not different from that of control rats. These data support the concept that the defect of neuromuscular transmission is due to a reduction of postsynaptic sensitivity to ACh."}
{"id": "PMID:211932", "title": "Pharmacological studies of the pupils in familial amyloid polyneuropathy.", "content": "Pharmacological studies of the pupils of 7 patients with familial amyloid polyneuropathy (FAP) were performed in order to demonstrate the site of the lesion. Supersensitivity to 1.25% epinephrine was observed frequently, but not to 2.5% methacholine. The lesions of the sympathetic nervous system, judging from the epinephrine and tyramine tests, were regarded as preganglionic in 2 patients and postganglionic in 4. Among 3 patients reexamined six months later, 1 had developed signs of sympathetic postganglionic disturbance and another showed a peripheral parasympathetic disturbance associated with progress of a sympathetic preganglionic disturbance. From these results it was suggested that in FAP, sympathetic abnormalities involve the pupils more often than parasympathetic disturbances, and pharmacological studies can detect the autonomic dysfunction before it becomes clinically apparent.", "contents": "Pharmacological studies of the pupils in familial amyloid polyneuropathy. Pharmacological studies of the pupils of 7 patients with familial amyloid polyneuropathy (FAP) were performed in order to demonstrate the site of the lesion. Supersensitivity to 1.25% epinephrine was observed frequently, but not to 2.5% methacholine. The lesions of the sympathetic nervous system, judging from the epinephrine and tyramine tests, were regarded as preganglionic in 2 patients and postganglionic in 4. Among 3 patients reexamined six months later, 1 had developed signs of sympathetic postganglionic disturbance and another showed a peripheral parasympathetic disturbance associated with progress of a sympathetic preganglionic disturbance. From these results it was suggested that in FAP, sympathetic abnormalities involve the pupils more often than parasympathetic disturbances, and pharmacological studies can detect the autonomic dysfunction before it becomes clinically apparent."}
{"id": "PMID:211933", "title": "Angiotensin converting enzyme in kainic acid--injected striata.", "content": "The activity of angiotensin converting enzyme is decreased in kainic acid-injected neostriata of rats, providing another biochemical similarity between this animal model and Huntington's chorea.", "contents": "Angiotensin converting enzyme in kainic acid--injected striata. The activity of angiotensin converting enzyme is decreased in kainic acid-injected neostriata of rats, providing another biochemical similarity between this animal model and Huntington's chorea."}
{"id": "PMID:211934", "title": "System for evaluating clostridial inhibition in cured meat products.", "content": "A method for evaluating inhibition of Clostridium botulinum, C. sporogenes, and C. perfringens in cured meat products was developed. This system can easily be used in the microbiology laboratory using aluminum ointment tubes as the product container. Swells caused by gas production by the organism are easily observed by using the aluminum tubes. Results obtained confirmed earlier work on the inhibitory effect of sodium nitrite and sorbic acid against the clostridia in cured meat products.", "contents": "System for evaluating clostridial inhibition in cured meat products. A method for evaluating inhibition of Clostridium botulinum, C. sporogenes, and C. perfringens in cured meat products was developed. This system can easily be used in the microbiology laboratory using aluminum ointment tubes as the product container. Swells caused by gas production by the organism are easily observed by using the aluminum tubes. Results obtained confirmed earlier work on the inhibitory effect of sodium nitrite and sorbic acid against the clostridia in cured meat products."}
{"id": "PMID:211935", "title": "Survey of human virus occurrence in wastewater-recharged groundwater on Long Island.", "content": "Treated wastewater effluents and groundwater observation wells from three sewage recharge installations located on Long Island were assayed on a monthly basis for indigenous human enteroviruses and coliform bacteria for a period of 1 year. Viruses were detected in groundwater at sites where recharge basins were located less than 35 feet (ca. 10.6 m) above the aquifer. Results from one of the sites indicated the horizontal transfer of viable viruses through the groundwater aquifer.", "contents": "Survey of human virus occurrence in wastewater-recharged groundwater on Long Island. Treated wastewater effluents and groundwater observation wells from three sewage recharge installations located on Long Island were assayed on a monthly basis for indigenous human enteroviruses and coliform bacteria for a period of 1 year. Viruses were detected in groundwater at sites where recharge basins were located less than 35 feet (ca. 10.6 m) above the aquifer. Results from one of the sites indicated the horizontal transfer of viable viruses through the groundwater aquifer."}
{"id": "PMID:211936", "title": "Poliovirus removal from primary and secondary sewage effluent by soil filtration.", "content": "Adsorption of poliovirus from primary sewage effluent was similar to that from secondary sewage effluent in both batch soil studies and experiments with soil columns 240 cm long. Virus desorption by distilled water was also similar in a soil column that had been flooded with either primary or secondary effluent seeded with virus. These results indicated that absorption of poliovirus from primary effluent and virus movement through the soil were not affected by the higher organic content of primary sewage effluent.", "contents": "Poliovirus removal from primary and secondary sewage effluent by soil filtration. Adsorption of poliovirus from primary sewage effluent was similar to that from secondary sewage effluent in both batch soil studies and experiments with soil columns 240 cm long. Virus desorption by distilled water was also similar in a soil column that had been flooded with either primary or secondary effluent seeded with virus. These results indicated that absorption of poliovirus from primary effluent and virus movement through the soil were not affected by the higher organic content of primary sewage effluent."}
{"id": "PMID:211937", "title": "Association of Yersinia enterocolitica with the manufacture of cheese and occurrence in pasteurized milk.", "content": "Raw milk in southern Ontario frequently contains Yersinia enterocolitica. The potential for transmission of this organism by cheese manufactured from unpasteurized milk was evaluated by examination of milk and cheese curd samples from cheese manufacturing plants and finished cheddar and Italian cheeses. The incidence of Y. enterocolitica was lower in cheese curd samples (9.2%) than in raw milk (18.2%). Most of the curd samples showed a positive phosphatase test, indicating production from raw milk. One curd sample yielded Y. enterocolitica after 4 weeks of storage at 4 degrees C but was negative after 8 weeks. All samples of cheddar and Italian cheeses, most of which showed a positive phosphatase test, were negative for Y. enterocolitica. One out of 265 samples (0.4%) of pasteurized fluid dairy products contained Y. enterocolitica.", "contents": "Association of Yersinia enterocolitica with the manufacture of cheese and occurrence in pasteurized milk. Raw milk in southern Ontario frequently contains Yersinia enterocolitica. The potential for transmission of this organism by cheese manufactured from unpasteurized milk was evaluated by examination of milk and cheese curd samples from cheese manufacturing plants and finished cheddar and Italian cheeses. The incidence of Y. enterocolitica was lower in cheese curd samples (9.2%) than in raw milk (18.2%). Most of the curd samples showed a positive phosphatase test, indicating production from raw milk. One curd sample yielded Y. enterocolitica after 4 weeks of storage at 4 degrees C but was negative after 8 weeks. All samples of cheddar and Italian cheeses, most of which showed a positive phosphatase test, were negative for Y. enterocolitica. One out of 265 samples (0.4%) of pasteurized fluid dairy products contained Y. enterocolitica."}
{"id": "PMID:211938", "title": "Reversible pulmonary oxygen toxicity in the primate.", "content": "In order to investigate the effects of high concentrations of oxygen on the lung, experiments were performed on 18 baboons exposed to a humidified environment of 95% oxygen for five days. Open lung biopsies for biochemical assay, histologic and electron microscopic analysis and measurement of tissue respiration were performed before and after oxygen exposure. Pulmonary function was evaluated by measurement of arterial blood gases, compliance, closing capacity (CC), functional residual capacity (FRC), total lung capacity (TLC), residual volume (RV) and vital capacity (VC) before and after exposure and then at seven and 14 days in the animals which recovered. Six baboons removed from the oxygen environment after 96--110 hours and exposed to room air died within three to 20 hours of profound hypoxemia (PaO2 40 +/- 6). The remaining 12 baboons were successfully weaned to room air over a three day period with a return of ABGs to control values (PaO2 89+/- 2). Electron microscopic analysis of alveolar membranes exposed to 120 hours of hyperoxia demonstrated endothelial cell swelling, interstitial alveolar membrane edema, and an increased predominance of Type II pneumocytes. Lung volume measurements showed significant decreases in TLC (25%), VC (34%), CC/TLC (28%) and dynamic compliance (47%). Biochemical studies indicated a shift toward anaerobic metabolism with a decrese in tissue oxygen consumption, reduced cytochrome oxidase activity, and increased lung lactic acid production. These changes were all found to be reversible in the 12 baboons slowly weaned back to room air.", "contents": "Reversible pulmonary oxygen toxicity in the primate. In order to investigate the effects of high concentrations of oxygen on the lung, experiments were performed on 18 baboons exposed to a humidified environment of 95% oxygen for five days. Open lung biopsies for biochemical assay, histologic and electron microscopic analysis and measurement of tissue respiration were performed before and after oxygen exposure. Pulmonary function was evaluated by measurement of arterial blood gases, compliance, closing capacity (CC), functional residual capacity (FRC), total lung capacity (TLC), residual volume (RV) and vital capacity (VC) before and after exposure and then at seven and 14 days in the animals which recovered. Six baboons removed from the oxygen environment after 96--110 hours and exposed to room air died within three to 20 hours of profound hypoxemia (PaO2 40 +/- 6). The remaining 12 baboons were successfully weaned to room air over a three day period with a return of ABGs to control values (PaO2 89+/- 2). Electron microscopic analysis of alveolar membranes exposed to 120 hours of hyperoxia demonstrated endothelial cell swelling, interstitial alveolar membrane edema, and an increased predominance of Type II pneumocytes. Lung volume measurements showed significant decreases in TLC (25%), VC (34%), CC/TLC (28%) and dynamic compliance (47%). Biochemical studies indicated a shift toward anaerobic metabolism with a decrese in tissue oxygen consumption, reduced cytochrome oxidase activity, and increased lung lactic acid production. These changes were all found to be reversible in the 12 baboons slowly weaned back to room air."}
{"id": "PMID:211940", "title": "[Ultramicroscopic structure of the cyst wall of Entamoeba invadens, E. histolytica and E. coli].", "content": "The ultrastructure of the wall of E. invadens cysts induced in axenic cultures was compared by transmission electron microscopy of thin sections, with that of E. histolytica and E. coli cysts obtained from feces of human asymptomatic carriers. The cyst wall of the three species studied had similar ultrastructural features; in all, the wall was composed mainly by the aggregation of filaments adjacent to the plasma membrane. The cytoplasmic components which might be involved in the synthesis and deposit of the cyst wall of E. invadens appear to be different to those of E. coli and E. histolytica cysts.", "contents": "[Ultramicroscopic structure of the cyst wall of Entamoeba invadens, E. histolytica and E. coli]. The ultrastructure of the wall of E. invadens cysts induced in axenic cultures was compared by transmission electron microscopy of thin sections, with that of E. histolytica and E. coli cysts obtained from feces of human asymptomatic carriers. The cyst wall of the three species studied had similar ultrastructural features; in all, the wall was composed mainly by the aggregation of filaments adjacent to the plasma membrane. The cytoplasmic components which might be involved in the synthesis and deposit of the cyst wall of E. invadens appear to be different to those of E. coli and E. histolytica cysts."}
{"id": "PMID:211941", "title": "[Instability of the DNA content in Entamoeba histolytica].", "content": "DNA content was repeatedly determined during a 10-month period on axenically cultured tropho-zoites from three strains (HK-9:NIH, HM-2:IMSS and HM-3:IMSS) and a clone of HK-9:NIH strain of Entamoeba histolytica, by means of the diphenylamine reaction. Average DNA content was more or less variable in all of them. According to their extent, variations were: 1) large (almost four times in strain HM-2:IMSS), or 2) small (1.5 times in the clonal isolate). With this relatively small sample, three statistically different groups were formed with nuclear DNA averages (1.35, 2.05 and 7.78 picograms respectively). Changes of ploidy and/or genomic heterogeneity in trophozoites could be the main causes of the striking instability in their DNA content.", "contents": "[Instability of the DNA content in Entamoeba histolytica]. DNA content was repeatedly determined during a 10-month period on axenically cultured tropho-zoites from three strains (HK-9:NIH, HM-2:IMSS and HM-3:IMSS) and a clone of HK-9:NIH strain of Entamoeba histolytica, by means of the diphenylamine reaction. Average DNA content was more or less variable in all of them. According to their extent, variations were: 1) large (almost four times in strain HM-2:IMSS), or 2) small (1.5 times in the clonal isolate). With this relatively small sample, three statistically different groups were formed with nuclear DNA averages (1.35, 2.05 and 7.78 picograms respectively). Changes of ploidy and/or genomic heterogeneity in trophozoites could be the main causes of the striking instability in their DNA content."}
{"id": "PMID:211943", "title": "[Amino acid composition in total proteins of strains of Entamoeba histolytica in axenic cultures].", "content": "In this paper we detail the amino acid composition of total protein hydrolyzates from trophozoites of two Entamoeba histolytica strains (HK-9:NIH and HM-2:IMSS) cultured axenically in TP-S-1 medium. Since we obtained nearly identical results in both strains, amino acid patterns may constitute an additional taxonomic criterion of the species. Our data are strikingly different from those found previously by other workers with total proteins from HK-9:NIH trophozoites cultured in a bacteria-conditioned medium; such difference emphasize the importance of axenic culture for the precise study of the chemical composition and metabolism of E. histolytica. Amino acid composition of total trophozoite proteins could be of use to attempt the design of a culture medium of defined amino acid content.", "contents": "[Amino acid composition in total proteins of strains of Entamoeba histolytica in axenic cultures]. In this paper we detail the amino acid composition of total protein hydrolyzates from trophozoites of two Entamoeba histolytica strains (HK-9:NIH and HM-2:IMSS) cultured axenically in TP-S-1 medium. Since we obtained nearly identical results in both strains, amino acid patterns may constitute an additional taxonomic criterion of the species. Our data are strikingly different from those found previously by other workers with total proteins from HK-9:NIH trophozoites cultured in a bacteria-conditioned medium; such difference emphasize the importance of axenic culture for the precise study of the chemical composition and metabolism of E. histolytica. Amino acid composition of total trophozoite proteins could be of use to attempt the design of a culture medium of defined amino acid content."}
{"id": "PMID:211939", "title": "[Pulmonary thromboembolism. Occlusion of the right branch of the pulmonary artery caused by lung cancer].", "content": "A rare case of an oat cell carcinoma is presented. The clinical picture were those of pulmonary thromboembolism and other extrapulmonary symptoms. There were not respiratory symptoms directly related to the lung carcinoma and the chest film remain normal.", "contents": "[Pulmonary thromboembolism. Occlusion of the right branch of the pulmonary artery caused by lung cancer]. A rare case of an oat cell carcinoma is presented. The clinical picture were those of pulmonary thromboembolism and other extrapulmonary symptoms. There were not respiratory symptoms directly related to the lung carcinoma and the chest film remain normal."}
{"id": "PMID:211944", "title": "Uptake of selected pyrimidines by axenically grown Entamoeba histolytica.", "content": "This study was conducted to determine the mode(s) of uptake of selected pyrimidine bases and nucleosides by axenically grown Entamoeba histolytica. Two-minute uptake studies with 3H-labeled compounds showed the following: 1) uridine and cytidine are taken up, in part, by a carrier mediated system; 2) uracil, cytosine, thymine and thymidine enter amebae via passive diffusion; both cytidine and uridine are taken up by passive diffusion when present at exogenous concentration greater than 500 muM; 3) specific carrier sites are used for transport of uridine-cytidine and uridine-adenosine; 4) cytidine and uridine uptake is markedly inhibited by iodoacetate and N-ethylmalemide; 5) hypoxanthine (10mM) stimulates uptake of uridine; 6) ribose fails to inhibit uptake of cytidine and uridine; 7) cytidine uptake exceeds that of uridine (i.e., apparent Vmax for: a) cytidine = 10.0 nmoles/2 min/10(6) amebae; b) uridine = 3.0 nmoles/2 min/10(6) amebae); 8) Kt for: cytidine = 0.30 mM; uridine = 0.21 mM; 9) Q 10's at 35.5 C vs 25.5 C for: a) cytidine = 3.9; b) uridine = 2.6.", "contents": "Uptake of selected pyrimidines by axenically grown Entamoeba histolytica. This study was conducted to determine the mode(s) of uptake of selected pyrimidine bases and nucleosides by axenically grown Entamoeba histolytica. Two-minute uptake studies with 3H-labeled compounds showed the following: 1) uridine and cytidine are taken up, in part, by a carrier mediated system; 2) uracil, cytosine, thymine and thymidine enter amebae via passive diffusion; both cytidine and uridine are taken up by passive diffusion when present at exogenous concentration greater than 500 muM; 3) specific carrier sites are used for transport of uridine-cytidine and uridine-adenosine; 4) cytidine and uridine uptake is markedly inhibited by iodoacetate and N-ethylmalemide; 5) hypoxanthine (10mM) stimulates uptake of uridine; 6) ribose fails to inhibit uptake of cytidine and uridine; 7) cytidine uptake exceeds that of uridine (i.e., apparent Vmax for: a) cytidine = 10.0 nmoles/2 min/10(6) amebae; b) uridine = 3.0 nmoles/2 min/10(6) amebae); 8) Kt for: cytidine = 0.30 mM; uridine = 0.21 mM; 9) Q 10's at 35.5 C vs 25.5 C for: a) cytidine = 3.9; b) uridine = 2.6."}
{"id": "PMID:211945", "title": "[Immunochemistry of immunogenic proteins of Entamoeba histolytica].", "content": "Entamoeba histolytica (HK-9: IMSS) trophozoites were separated from the culture medium and washed and submitted to the effects of ultrasound during 10 minutes. After 10,000 rpm x 30 centrifugation, the supernatant fluid was separated in four fractions by Sephadex G-200 gel chromatography. These fractions were lyophilized, redisolved in a lesser volume and dyalized against isotonic saline solution. Antigen-antibody precipitant reactions between each of them and two rabbit antiserums were demonstrated: anti amoeba and anti fraction A. It was verified that the antisera reacted also with the culture medium, the human seric albumin and the sera from health people and patients with invasive amebiasis. The higher antigenicity, quantitatively and qualitatively, was obtained with the fraction B; the less antigenic fraction was the fraction D. In fraction A three antigens were identified. When those proteins were filtered by a Bio Gel P4 column, two fractions were eluted: A1 and A2 which were lyophilized, redisolved and dyalized in isotonic saline solution. After this treatment, fraction A1 was capable to maintain its antigenicity against the rabbit antisera and the sera from patients with invasive amebiasis, fact by which it was considered a protein from amebal origin and not as a protenic contaminant from the culture medium.", "contents": "[Immunochemistry of immunogenic proteins of Entamoeba histolytica]. Entamoeba histolytica (HK-9: IMSS) trophozoites were separated from the culture medium and washed and submitted to the effects of ultrasound during 10 minutes. After 10,000 rpm x 30 centrifugation, the supernatant fluid was separated in four fractions by Sephadex G-200 gel chromatography. These fractions were lyophilized, redisolved in a lesser volume and dyalized against isotonic saline solution. Antigen-antibody precipitant reactions between each of them and two rabbit antiserums were demonstrated: anti amoeba and anti fraction A. It was verified that the antisera reacted also with the culture medium, the human seric albumin and the sera from health people and patients with invasive amebiasis. The higher antigenicity, quantitatively and qualitatively, was obtained with the fraction B; the less antigenic fraction was the fraction D. In fraction A three antigens were identified. When those proteins were filtered by a Bio Gel P4 column, two fractions were eluted: A1 and A2 which were lyophilized, redisolved and dyalized in isotonic saline solution. After this treatment, fraction A1 was capable to maintain its antigenicity against the rabbit antisera and the sera from patients with invasive amebiasis, fact by which it was considered a protein from amebal origin and not as a protenic contaminant from the culture medium."}
{"id": "PMID:211946", "title": "[Cytopathogenic activity of extracts E. histolytica trophozoites].", "content": "Previous studies have not shown any correlation between enzyme activities and pathogenicity of Entamoeba histolytica. The activities analyzed were selected without having proved their involvement in the cytopathogenicity. We are using the reverse approach to study the cytopathogenic factors, i.e., to detect and characterize first the cytopathic effect of amebic extracts on animal cells, and subsequently to try to identify the components involved and to explore their correlation with amebic virulence. Total extracts from E. histolytica trophozoites exert dosedependent toxic and lytic effects upon an animal cell line in culture. Erythocytes from eight mammaliam species have been used as a simple target model for the characterization of the cytolytic affect. Hemolysis by amebic extracts is consistent, reproducible, strain specific and dosedependent. Hemolytic potency is much larger E. histolytica extracts than those from other Entamoeba species. This work appears to open up the study of the biochemical basis of E. histolytica cytopathogenicity.", "contents": "[Cytopathogenic activity of extracts E. histolytica trophozoites]. Previous studies have not shown any correlation between enzyme activities and pathogenicity of Entamoeba histolytica. The activities analyzed were selected without having proved their involvement in the cytopathogenicity. We are using the reverse approach to study the cytopathogenic factors, i.e., to detect and characterize first the cytopathic effect of amebic extracts on animal cells, and subsequently to try to identify the components involved and to explore their correlation with amebic virulence. Total extracts from E. histolytica trophozoites exert dosedependent toxic and lytic effects upon an animal cell line in culture. Erythocytes from eight mammaliam species have been used as a simple target model for the characterization of the cytolytic affect. Hemolysis by amebic extracts is consistent, reproducible, strain specific and dosedependent. Hemolytic potency is much larger E. histolytica extracts than those from other Entamoeba species. This work appears to open up the study of the biochemical basis of E. histolytica cytopathogenicity."}
{"id": "PMID:211947", "title": "[Effects of nordihydroguairetic acid and ethanol on the growth of Entamoeba invadens].", "content": "The effects of the alcoholic extract (resin) obtained from Larrea tridentata, of nordihydroguiaretic acid (NDGA) and of ethanol over axenic cultures of Entamoeba invadens PZ strain were studied. The activity of these substances was demonstrated in growht curves. Inocula of 1-3 x 10(5) trophozites by milliliter in culture tubes containing 11 ml of TP-S-1 medium were done, and incubated at 25 degree C. In each experiment the follwoing was done: a) tipical growth curve as a control, b) curve with the medium plus 0.2 ml of a mixture of ethanol and water v/v  (solvent used for resin and NDGA), and c) curves with different concentrations of the test compounds. The trophozoite number was counted each 24 hours by means of an hemocitometer. The results obtained indicate that the resin has inhibitory activity at a concentration of 0.0001 per  cent. The NDGA activity was observed at 10(-6) to 10(-8) M concentrations. The ethanol had, \"per se\", inhibitory effect over the cultures, and was annulated by the  presence of NDGA. At higher contentrations of the acid acid the temporal curse of the graphas was similar to that observed for the control.", "contents": "[Effects of nordihydroguairetic acid and ethanol on the growth of Entamoeba invadens]. The effects of the alcoholic extract (resin) obtained from Larrea tridentata, of nordihydroguiaretic acid (NDGA) and of ethanol over axenic cultures of Entamoeba invadens PZ strain were studied. The activity of these substances was demonstrated in growht curves. Inocula of 1-3 x 10(5) trophozites by milliliter in culture tubes containing 11 ml of TP-S-1 medium were done, and incubated at 25 degree C. In each experiment the follwoing was done: a) tipical growth curve as a control, b) curve with the medium plus 0.2 ml of a mixture of ethanol and water v/v  (solvent used for resin and NDGA), and c) curves with different concentrations of the test compounds. The trophozoite number was counted each 24 hours by means of an hemocitometer. The results obtained indicate that the resin has inhibitory activity at a concentration of 0.0001 per  cent. The NDGA activity was observed at 10(-6) to 10(-8) M concentrations. The ethanol had, \"per se\", inhibitory effect over the cultures, and was annulated by the  presence of NDGA. At higher contentrations of the acid acid the temporal curse of the graphas was similar to that observed for the control."}
{"id": "PMID:211951", "title": "The development and standaridization of an ELISA method for the detection of Entamoeba histolytica antigens in fecal samples.", "content": "Recognizing the difficluties associated with the microscopic detection and identification of Entamoeba histolytica in fecal samples, an immunochemical method of detection of E. histolytica antigens in fe-es has been developed. For a number of reasons, e.g., the known fragility of E. histolytica trophozoites, it was felt that intestinal amebiasis would be associated with detectable levels of E. histolytica anti-ens in feces from infected patients. A technique for harvesting amebic antigens in fecal samples was developed. An enzyme labeled antibody technique was used to visualize the harvested antigens. The inherent problems of performing any immunochemical assay in fecal samples have been addressed. The enzyme labeled antibody method is simple and is designed to be more sensitive than microscopic stool examination methods. Preliminary results indicate that the method is specific and sensitive.", "contents": "The development and standaridization of an ELISA method for the detection of Entamoeba histolytica antigens in fecal samples. Recognizing the difficluties associated with the microscopic detection and identification of Entamoeba histolytica in fecal samples, an immunochemical method of detection of E. histolytica antigens in fe-es has been developed. For a number of reasons, e.g., the known fragility of E. histolytica trophozoites, it was felt that intestinal amebiasis would be associated with detectable levels of E. histolytica anti-ens in feces from infected patients. A technique for harvesting amebic antigens in fecal samples was developed. An enzyme labeled antibody technique was used to visualize the harvested antigens. The inherent problems of performing any immunochemical assay in fecal samples have been addressed. The enzyme labeled antibody method is simple and is designed to be more sensitive than microscopic stool examination methods. Preliminary results indicate that the method is specific and sensitive."}
{"id": "PMID:211952", "title": "[Identification of Entamoeba histolytica membrane antigens with antibodies of amebiasis patients].", "content": "The specificity of sera from patients with amoebiasis was assayed on trophozoites of E. histolytica HK9, HM15 and HM2 cultured axenically and monoxenically. Glutaraldehyde fixed cell were incubated with samples of serum, the excess of Igs was washed out and the presence of unbound material of specifically bound antibodies was measured with radiolabeled protein A from Staphylococcus aureus. A positive reaction with HK9 was observed in 18 per cent of the 66 sera tested. An immune crossreaction resulted with HM2 and HM15, while no reaction was observed with the nonpathogenic strains E. invadens, E. moshkovskii and E. laredo.", "contents": "[Identification of Entamoeba histolytica membrane antigens with antibodies of amebiasis patients]. The specificity of sera from patients with amoebiasis was assayed on trophozoites of E. histolytica HK9, HM15 and HM2 cultured axenically and monoxenically. Glutaraldehyde fixed cell were incubated with samples of serum, the excess of Igs was washed out and the presence of unbound material of specifically bound antibodies was measured with radiolabeled protein A from Staphylococcus aureus. A positive reaction with HK9 was observed in 18 per cent of the 66 sera tested. An immune crossreaction resulted with HM2 and HM15, while no reaction was observed with the nonpathogenic strains E. invadens, E. moshkovskii and E. laredo."}
{"id": "PMID:211953", "title": "[Phagocytosis of human erythrocytes by Entamoeba histolytica. Quantitative study].", "content": "The degree of eythrophagocytosis of two recently isolated strains of E. histolytica was measured by microscopic examination. Amebas isolated from a patient with amebic rectocolitis (strain HM22:IMSS, monoxenic) ingested human red blood cells faster and in larger numbers than trophozoites isolated from an asymptomatic carrier (HM27:IMSS, monoxenic). The results suggest that an increased rate of phagocytosis could be one of the surface properties characteristic of the invasive strains of E. histolytica.", "contents": "[Phagocytosis of human erythrocytes by Entamoeba histolytica. Quantitative study]. The degree of eythrophagocytosis of two recently isolated strains of E. histolytica was measured by microscopic examination. Amebas isolated from a patient with amebic rectocolitis (strain HM22:IMSS, monoxenic) ingested human red blood cells faster and in larger numbers than trophozoites isolated from an asymptomatic carrier (HM27:IMSS, monoxenic). The results suggest that an increased rate of phagocytosis could be one of the surface properties characteristic of the invasive strains of E. histolytica."}
{"id": "PMID:211954", "title": "Production of cecal lesions in newborn guinea pigs with axenically cultivated Entamoeba histolytica.", "content": "The production of cecal lesions with axenically cultivated Entamoeba histolytica in an experimental animal is reported for the first time. Forty-three newborn guinea pigs (one to five days old) were inoculated via laparatomy with 2.5 x 10(5) to 2 x 10(6) strain HM-1-IMSS amebae. Of 23 animals surviving to the 7th postinoculation day all showed cecal lesions at necropsy regardless of the age of the animal when used or the number of amebae received. Ten animals had lesions visible to the unaided eye and 13 had only microscopic lesions. No lesions were noted in other organs of the abdominal or thoracic regiosn. The use of axenically cultivated ameabae in newborn guinea pigs should prove a useful experimental model for the study of amebiasis.", "contents": "Production of cecal lesions in newborn guinea pigs with axenically cultivated Entamoeba histolytica. The production of cecal lesions with axenically cultivated Entamoeba histolytica in an experimental animal is reported for the first time. Forty-three newborn guinea pigs (one to five days old) were inoculated via laparatomy with 2.5 x 10(5) to 2 x 10(6) strain HM-1-IMSS amebae. Of 23 animals surviving to the 7th postinoculation day all showed cecal lesions at necropsy regardless of the age of the animal when used or the number of amebae received. Ten animals had lesions visible to the unaided eye and 13 had only microscopic lesions. No lesions were noted in other organs of the abdominal or thoracic regiosn. The use of axenically cultivated ameabae in newborn guinea pigs should prove a useful experimental model for the study of amebiasis."}
{"id": "PMID:211955", "title": "[Culture and establishment of new Mexican Strains of Entamoeba histolytica].", "content": "Mixed and monoxenic cultures of rectal exudates from three patients with amebiasis of colon, and of feces from three asymptomatic carriers of Entamoeba histolytica obtained after administration of a saline cathartic, and from a case of exudate of the perianal cutaneous lesion border produced by this parasite, were done. The culture media used were for: mixed culture, Boeck and Drbohlav modified culture and, for monoxenic culture, Diamond's monophasic TP-S-1 medium without vitamin mixture and using bovine serum. In order to inhibit the bacterial growth in the mixed culture, streptomycin sulphate and pencillin G were used. In order to eliminate the bacterial flora kanamicin sulphate, chloramphenicol, gentamycin and disodic carbenicillin were added. Mixed cultures of seven strains of Entamoeba histolytica were obtained: HM22:IMSS, HM23:IMSS, HM24:IMSS, HM26:IMSS, HM27:IMSS, HM28:IMSS y HM29:IMSS, and monoxenic culture with Bacteroids symbiosus of the strains HM22:IMSS and HM27:IMSS, with a previous adaptation in mixed culture. The adaptation of HM26:IMSS strain in monoxenic culture was obtained by means of direct seeding of the rectal exudate with Fusobacterium symbiosus.", "contents": "[Culture and establishment of new Mexican Strains of Entamoeba histolytica]. Mixed and monoxenic cultures of rectal exudates from three patients with amebiasis of colon, and of feces from three asymptomatic carriers of Entamoeba histolytica obtained after administration of a saline cathartic, and from a case of exudate of the perianal cutaneous lesion border produced by this parasite, were done. The culture media used were for: mixed culture, Boeck and Drbohlav modified culture and, for monoxenic culture, Diamond's monophasic TP-S-1 medium without vitamin mixture and using bovine serum. In order to inhibit the bacterial growth in the mixed culture, streptomycin sulphate and pencillin G were used. In order to eliminate the bacterial flora kanamicin sulphate, chloramphenicol, gentamycin and disodic carbenicillin were added. Mixed cultures of seven strains of Entamoeba histolytica were obtained: HM22:IMSS, HM23:IMSS, HM24:IMSS, HM26:IMSS, HM27:IMSS, HM28:IMSS y HM29:IMSS, and monoxenic culture with Bacteroids symbiosus of the strains HM22:IMSS and HM27:IMSS, with a previous adaptation in mixed culture. The adaptation of HM26:IMSS strain in monoxenic culture was obtained by means of direct seeding of the rectal exudate with Fusobacterium symbiosus."}
{"id": "PMID:211956", "title": "Cytotoxicity of a cell free extract of Entamoeba histolytica.", "content": "Previous attempts to demonstrate toxicity of cell-free extracts prepared from axenically cultivated E. histolytica have proved unsuccessful. We report here the successful production of cytopathic effect by cell-free extracts of two strains (HM-1 and HK-9) of E. histolytica in tissue culture monolayers. The cytotoxic effect demonstrated was sensitive to serum in the assay medium. Failure of past investigations to demonstrate cytotoxic activity may be explained by the presence of serum in the assay systems used.", "contents": "Cytotoxicity of a cell free extract of Entamoeba histolytica. Previous attempts to demonstrate toxicity of cell-free extracts prepared from axenically cultivated E. histolytica have proved unsuccessful. We report here the successful production of cytopathic effect by cell-free extracts of two strains (HM-1 and HK-9) of E. histolytica in tissue culture monolayers. The cytotoxic effect demonstrated was sensitive to serum in the assay medium. Failure of past investigations to demonstrate cytotoxic activity may be explained by the presence of serum in the assay systems used."}
{"id": "PMID:211957", "title": "Clonal growth of Entamoeba in agar: some applications of this technique to the study of their cell biology.", "content": "A new technique for growing single Entamoeba trophozoites into colonies in agar has been developed. This method depended upon axenic cultivation and utilized Diamond's new TYI-S-33 medium. The present paper describes several different types of experiment which have utilized the agar technique. a) Cloning. The isolation of clones from agar way easy and successful. Clones of the HM-1 strain did not differ in virulence for newborn hamster liver or in colony morphology or colony forming efficiency. b) Viability measurements. Colony forming efficiency (CFE) was proportional to the number of viable cells in a culture. Pilot studies with the amebacides, metronidazole and emetine, showed that the agar method should be useful in drug testing. Colchicine at high concentration inhibited clonal growth in a non-specific manner. c) E. histolytica HM-1 and E. invadens cells were rapidly killed by exposure to 42 degree C but survived relatively well at 0 degree C. d) Hemolysis. In a preliminary experiment HM-1 colonies did not produce halo's of hemolysis when grown in agar containing sheep red blood cells.", "contents": "Clonal growth of Entamoeba in agar: some applications of this technique to the study of their cell biology. A new technique for growing single Entamoeba trophozoites into colonies in agar has been developed. This method depended upon axenic cultivation and utilized Diamond's new TYI-S-33 medium. The present paper describes several different types of experiment which have utilized the agar technique. a) Cloning. The isolation of clones from agar way easy and successful. Clones of the HM-1 strain did not differ in virulence for newborn hamster liver or in colony morphology or colony forming efficiency. b) Viability measurements. Colony forming efficiency (CFE) was proportional to the number of viable cells in a culture. Pilot studies with the amebacides, metronidazole and emetine, showed that the agar method should be useful in drug testing. Colchicine at high concentration inhibited clonal growth in a non-specific manner. c) E. histolytica HM-1 and E. invadens cells were rapidly killed by exposure to 42 degree C but survived relatively well at 0 degree C. d) Hemolysis. In a preliminary experiment HM-1 colonies did not produce halo's of hemolysis when grown in agar containing sheep red blood cells."}
{"id": "PMID:211958", "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 five and six 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 five and six 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:211959", "title": "[An in vitro model for the quantitative study of E. histolytica virulence].", "content": "An experimental model for the quantitative study of the cytopathic effect of E. histolytica is described. Confluent cultures of the MDCK cell line, which form a monolayer with morphological and electrophysiological features of an epithelium were used. Trophozoites of the strains HM1:IMSS, HM2:IMSS and HM3:IMSS, axenic produced variable degrees of cytopathic effects of MDCK cultures each one characteristic for a given strain. The degree of damage induced by the different strains of amebas was measured quantitatively. The results demonstrate that the degree of the cytopathic effect produced in vitro by the various strains tested correlates with the virulence shown in vivo by the same strains, judged as the size of the inoculum required to induce liver cytopathic effect in newborn hamsters.", "contents": "[An in vitro model for the quantitative study of E. histolytica virulence]. An experimental model for the quantitative study of the cytopathic effect of E. histolytica is described. Confluent cultures of the MDCK cell line, which form a monolayer with morphological and electrophysiological features of an epithelium were used. Trophozoites of the strains HM1:IMSS, HM2:IMSS and HM3:IMSS, axenic produced variable degrees of cytopathic effects of MDCK cultures each one characteristic for a given strain. The degree of damage induced by the different strains of amebas was measured quantitatively. The results demonstrate that the degree of the cytopathic effect produced in vitro by the various strains tested correlates with the virulence shown in vivo by the same strains, judged as the size of the inoculum required to induce liver cytopathic effect in newborn hamsters."}
{"id": "PMID:211960", "title": "[Interaction between Entamoeba histolytica and the cecal epithelium in the guinea pig].", "content": "The early interaction between  E. histolytica trophozoites and the intestinal mucosa was studied by light and electron microscopy using sheets of isolated epithelium of the guinea pig colonic mucosa. The integrity of the isolated epithelium was confirmed by scanning electron microscopy. After 30 minutes of interaction, the amebas adhered first, and penetrated subsecuently the epithelium of the colon at the interglandular regions. The results suggest that the trophozoites of E. histolytica invade the epithelial barrier exclusively at the regions of lowest resistence, represented by the interglandular zones of epithelial shedding.", "contents": "[Interaction between Entamoeba histolytica and the cecal epithelium in the guinea pig]. The early interaction between  E. histolytica trophozoites and the intestinal mucosa was studied by light and electron microscopy using sheets of isolated epithelium of the guinea pig colonic mucosa. The integrity of the isolated epithelium was confirmed by scanning electron microscopy. After 30 minutes of interaction, the amebas adhered first, and penetrated subsecuently the epithelium of the colon at the interglandular regions. The results suggest that the trophozoites of E. histolytica invade the epithelial barrier exclusively at the regions of lowest resistence, represented by the interglandular zones of epithelial shedding."}
{"id": "PMID:211961", "title": "[Ultramicroscopic study of the invasion of the mucosa of the colon by Entamoeba histolytica in axenic cultures].", "content": "Animal models have been utilized to study experimentally produced intestinal amebiasis. The guinea pig has been the animal of choice to study the mechanisms by which trophozoites of E. histolytica produce colonic lesions. The purpose of this study was to produce lesions in the colon of newborn guinea pigs by the injection of E. histolytica, HM-1 IMSS, strain grown axenically, and to characterize the early changes with the light and electron microscopes. A total of 35 guinea pigs, one to two days old, were inoculated into the cecum with one and a half million of trophozoites of E. histolytica. Thirteen surviving animals were sacrificed. In four there were clear cut amebic lesions. Sections were taken from neighbouring transitional zones. The most important changes were the migrations of trophozoites to the bottom of colonic glands with many parasites located within the crypts. There was passage of ameabae to the lamina propia with practically no inflammatory reaction. It is thought that the parasite, in contact with epithelial crypt cell, produce direct lysis of these elements leading to migration of amebae into the lamina propia.", "contents": "[Ultramicroscopic study of the invasion of the mucosa of the colon by Entamoeba histolytica in axenic cultures]. Animal models have been utilized to study experimentally produced intestinal amebiasis. The guinea pig has been the animal of choice to study the mechanisms by which trophozoites of E. histolytica produce colonic lesions. The purpose of this study was to produce lesions in the colon of newborn guinea pigs by the injection of E. histolytica, HM-1 IMSS, strain grown axenically, and to characterize the early changes with the light and electron microscopes. A total of 35 guinea pigs, one to two days old, were inoculated into the cecum with one and a half million of trophozoites of E. histolytica. Thirteen surviving animals were sacrificed. In four there were clear cut amebic lesions. Sections were taken from neighbouring transitional zones. The most important changes were the migrations of trophozoites to the bottom of colonic glands with many parasites located within the crypts. There was passage of ameabae to the lamina propia with practically no inflammatory reaction. It is thought that the parasite, in contact with epithelial crypt cell, produce direct lysis of these elements leading to migration of amebae into the lamina propia."}
{"id": "PMID:211962", "title": "[Serology with polysaccharides of Entamoeba histolytica].", "content": "The immunochemical activity of a polysaccharidic antigen derivated from E. histolytica was studied. This polysaccharide was tested by means of counterimmunoelectrophoresis (CIE) and radial immunodiffusion (IDR) against sera from patients with diagnosis of intestinal and hepatic amebiasis. In order to perform a test most significative to the problem sera, these were submitted previously to passive hemagglutination, CIE and IDR with total ameba antigen. In hepatic amebiasis it can be observed that the CIE done with commercial antigen is practically negative in all cases; incontrast, the test performed with total antigen was positive in almost all the cases. Passive hemagglutination with sheep red blood cells, tanned and sensibilized with total ameba antigen gave very high titers when the problem was amebic hepatic abscess, and very low when the problem was intestinal amebiasis. Counterimmunoelectrophoresis and radial diffusion were negative with polysaccharidic antigen in all the studied sera.", "contents": "[Serology with polysaccharides of Entamoeba histolytica]. The immunochemical activity of a polysaccharidic antigen derivated from E. histolytica was studied. This polysaccharide was tested by means of counterimmunoelectrophoresis (CIE) and radial immunodiffusion (IDR) against sera from patients with diagnosis of intestinal and hepatic amebiasis. In order to perform a test most significative to the problem sera, these were submitted previously to passive hemagglutination, CIE and IDR with total ameba antigen. In hepatic amebiasis it can be observed that the CIE done with commercial antigen is practically negative in all cases; incontrast, the test performed with total antigen was positive in almost all the cases. Passive hemagglutination with sheep red blood cells, tanned and sensibilized with total ameba antigen gave very high titers when the problem was amebic hepatic abscess, and very low when the problem was intestinal amebiasis. Counterimmunoelectrophoresis and radial diffusion were negative with polysaccharidic antigen in all the studied sera."}
{"id": "PMID:211963", "title": "[Activity of the alternative complement pathway by various axenic strains of Entamoeba histolytica].", "content": "The activation of the alternative pathway of complement by axenic cultures of E. histolytica is reported. The activation is carried out in different proportions by several axenic strains, i.e., HK9:NIH, HM1:IMSS, HM2:IMSS and HM3:IMSS; the end result consists of a destruction of the parasite as well as consumption of the serum complement. The participation of the alternative pathway was studied in the presence of EGTA and Mg++, zymosan, heat-inactivation at 50 degree C for 20 min and immunoelectrophoretic studied with anti-factor B.", "contents": "[Activity of the alternative complement pathway by various axenic strains of Entamoeba histolytica]. The activation of the alternative pathway of complement by axenic cultures of E. histolytica is reported. The activation is carried out in different proportions by several axenic strains, i.e., HK9:NIH, HM1:IMSS, HM2:IMSS and HM3:IMSS; the end result consists of a destruction of the parasite as well as consumption of the serum complement. The participation of the alternative pathway was studied in the presence of EGTA and Mg++, zymosan, heat-inactivation at 50 degree C for 20 min and immunoelectrophoretic studied with anti-factor B."}
{"id": "PMID:211964", "title": "[Immunite reaction of hamsters infected or immunized with Entamoeba histolytica].", "content": "The immune response in hamsters either infected or immunized with Entamoeba histolytica was studied. The response was tested by determination of antibodies by the counterimmunoelectrophoresis technique and by lymphocyte transformation induced by the amebic antigen. The results obtained showed differences among both groups when the ability of amebic antigen to induce 3H-thymidine incorporation of lymphocyte cultures is compared. However, the response of lymphocyte cultures to Concanavalin A was similar in both studied groups. On the other hand, a group of hamsters hyperimmunized with E. histolytica antigen incorporated in complete Frend's adjuvant showed a greater immune response than the group receiving a single dose.", "contents": "[Immunite reaction of hamsters infected or immunized with Entamoeba histolytica]. The immune response in hamsters either infected or immunized with Entamoeba histolytica was studied. The response was tested by determination of antibodies by the counterimmunoelectrophoresis technique and by lymphocyte transformation induced by the amebic antigen. The results obtained showed differences among both groups when the ability of amebic antigen to induce 3H-thymidine incorporation of lymphocyte cultures is compared. However, the response of lymphocyte cultures to Concanavalin A was similar in both studied groups. On the other hand, a group of hamsters hyperimmunized with E. histolytica antigen incorporated in complete Frend's adjuvant showed a greater immune response than the group receiving a single dose."}
{"id": "PMID:211969", "title": "[A new hemagglutination method to determine antibodies against Entamoeba histolytica].", "content": "A passive hemagglutination method useful for the determination of antibodies against Entamoeba histolytica is described. The E. histolytica antigen is attached to group \"O\" human red blood cells by means of CrCl3. The specificity and sensitivity of the CrCl3 method was compared with other hemagglutination methods, i.e., tannic acid method and a commercial preparation, as well as counterimmunoelectrophoresis. The CrCl3 method showed a reactivity similar to the tannic acid hemagglutination technique and greater specificity than the commercial preparation. The assay reported here showed a good correlation with the counterimmunoelectrophoresis method. The sensitization of erythrocytes with the amebic antigen by means of CrCl3 offers an easy, rapid and specific technique which can be used as a routine test for the detection of antibodies against E. histolytica.", "contents": "[A new hemagglutination method to determine antibodies against Entamoeba histolytica]. A passive hemagglutination method useful for the determination of antibodies against Entamoeba histolytica is described. The E. histolytica antigen is attached to group \"O\" human red blood cells by means of CrCl3. The specificity and sensitivity of the CrCl3 method was compared with other hemagglutination methods, i.e., tannic acid method and a commercial preparation, as well as counterimmunoelectrophoresis. The CrCl3 method showed a reactivity similar to the tannic acid hemagglutination technique and greater specificity than the commercial preparation. The assay reported here showed a good correlation with the counterimmunoelectrophoresis method. The sensitization of erythrocytes with the amebic antigen by means of CrCl3 offers an easy, rapid and specific technique which can be used as a routine test for the detection of antibodies against E. histolytica."}
{"id": "PMID:211971", "title": "Effect of carbon source on enzymes involved in glycerol metabolism in Neurospora crassa.", "content": "Specific activities of eight enzymes involved in glycerol metabolism were determined in crude extracts of three strains of Neurospora crassa after growth on six different carbon sources. One of the strains was wild type, which grew poorly on glycerol as sole carbon source; the other two were mutant strains which were efficient glycerol utilizers. A possible basis for this greater efficiency of glycerol utilization was catabolite repression of glyceraldehyde kinase by glycerol in wild type, and two-fold higher glycerate kinase activity in the mutant strains after growth on glycerol, thus apparently allowing two routes for glyceraldehyde to enter the glycolytic pathway in the mutant strains but only one in wild type. The preferential entry of glyceraldehyde to the glycolytic pathway through glycerate was suggested by the lack of glyceraldehyde kinase in all three strains after growth on one or more of the carbon sources and the generally higher levels of aldehyde dehydrogenase and of glycerate kinase than of glyceraldehyde kinase.", "contents": "Effect of carbon source on enzymes involved in glycerol metabolism in Neurospora crassa. Specific activities of eight enzymes involved in glycerol metabolism were determined in crude extracts of three strains of Neurospora crassa after growth on six different carbon sources. One of the strains was wild type, which grew poorly on glycerol as sole carbon source; the other two were mutant strains which were efficient glycerol utilizers. A possible basis for this greater efficiency of glycerol utilization was catabolite repression of glyceraldehyde kinase by glycerol in wild type, and two-fold higher glycerate kinase activity in the mutant strains after growth on glycerol, thus apparently allowing two routes for glyceraldehyde to enter the glycolytic pathway in the mutant strains but only one in wild type. The preferential entry of glyceraldehyde to the glycolytic pathway through glycerate was suggested by the lack of glyceraldehyde kinase in all three strains after growth on one or more of the carbon sources and the generally higher levels of aldehyde dehydrogenase and of glycerate kinase than of glyceraldehyde kinase."}
{"id": "PMID:211974", "title": "Cyclic AMP and cyclic GMP in germinating conidia of Neurospora crassa.", "content": "A new method for obtaining synchronous germination allowed accurate time-course studies of endogenous levels of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-phosphate in germinating conidia of Neurospora crassa. The levels of both cyclic nucleotides remained constant throughout germination, showing that they neither signal nor respond to any of the biochemical changes which are known to occur in the germination process. Conidal germination was approximately normal in three cr-1 mutants of Neurospora which have been shown to be deficient in adenylate cyclase activity. Cyclic AMP levels in the mycelia of cr-1 mutants were low, but surprisingly, the levels in conidia were normal.", "contents": "Cyclic AMP and cyclic GMP in germinating conidia of Neurospora crassa. A new method for obtaining synchronous germination allowed accurate time-course studies of endogenous levels of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-phosphate in germinating conidia of Neurospora crassa. The levels of both cyclic nucleotides remained constant throughout germination, showing that they neither signal nor respond to any of the biochemical changes which are known to occur in the germination process. Conidal germination was approximately normal in three cr-1 mutants of Neurospora which have been shown to be deficient in adenylate cyclase activity. Cyclic AMP levels in the mycelia of cr-1 mutants were low, but surprisingly, the levels in conidia were normal."}
{"id": "PMID:211975", "title": "Effect of temperature on diauxic growth with glucose and organic acids in Pseudomonas fluorescens.", "content": "Growth of Pseudomonas fluorescens in batch culture with glucose and organic acids resulted in typical diauxic responses at 30 degrees C but no detectable diauxic lag at 5 degrees C. At 30 degrees C, organic acids were preferentially utilized during the first growth phase. Glucose utilization was delayed until onset of the second growth phase. Systems involved in direct uptake and catabolism of glucose responded in a manner compatible with repression by malate and/or its metabolites and induction by glucose and/or its metabolites. The oxidative non-phosphorylated pathway, through gluconate and 2-ketogluconate (2-KG) as intermediates, was not induced during either growth phase. At 5 degrees C, growth with glucose and organic acids was biphasic but without diauxic lag. Organic acids were preferentially utilized during the first growth phase. Although carbon from glucose was not fully catabolized until onset of the second growth phase, glucose was oxidized to and accumulated extracellularly as gluconate and 2-KG during the first growth phase. No significant repression of glucose-catabolizing enzymes was observed during growth with organic acids in the presence of glucose. However, uptake activities for gluconate and 2-KG did not increase significantly until onset of the second growth phase. Thus, at low temperatures, psychotrophic P. fluorescens oxidized glucose to extracellular 2-KG, while growing on preferred carbon sources. The 2-KG was then catabolized after depletion of the organic acid.", "contents": "Effect of temperature on diauxic growth with glucose and organic acids in Pseudomonas fluorescens. Growth of Pseudomonas fluorescens in batch culture with glucose and organic acids resulted in typical diauxic responses at 30 degrees C but no detectable diauxic lag at 5 degrees C. At 30 degrees C, organic acids were preferentially utilized during the first growth phase. Glucose utilization was delayed until onset of the second growth phase. Systems involved in direct uptake and catabolism of glucose responded in a manner compatible with repression by malate and/or its metabolites and induction by glucose and/or its metabolites. The oxidative non-phosphorylated pathway, through gluconate and 2-ketogluconate (2-KG) as intermediates, was not induced during either growth phase. At 5 degrees C, growth with glucose and organic acids was biphasic but without diauxic lag. Organic acids were preferentially utilized during the first growth phase. Although carbon from glucose was not fully catabolized until onset of the second growth phase, glucose was oxidized to and accumulated extracellularly as gluconate and 2-KG during the first growth phase. No significant repression of glucose-catabolizing enzymes was observed during growth with organic acids in the presence of glucose. However, uptake activities for gluconate and 2-KG did not increase significantly until onset of the second growth phase. Thus, at low temperatures, psychotrophic P. fluorescens oxidized glucose to extracellular 2-KG, while growing on preferred carbon sources. The 2-KG was then catabolized after depletion of the organic acid."}
{"id": "PMID:211978", "title": "[Current status of immunoprophylaxis against foot-and-mouth disease].", "content": "An analysis is made of the latest developments and importance of immunoprophylaxis against FMD, with reference to the epizootiological situation of the disease and its bearings, today, on industrialized livestock production. Comprehensive immunoprophylactic action (vaccination of all cattle every year) has been taken first by the GDR and later on by more European countries, as well. As a result of such action the disastrous impact of FMD and its associated high loss rate have been considerably mitigated. A decisive role, in that context, has been played by the development of effective inactivated vaccines for swine. An FMD live vaccine has been devised in GDR for after-care of swine. It is not only harmless to the animal, but, as well known, it provides numerous advantages over adsorbate vaccines. FMD immunoprophylaxis for full success depends primarily on the proper selection of virus strains suitable for vaccine produktion, vaccine quality, avoidance of post-vaccination damage or disease, and the availability of an efficient concept for vaccine application. The above problems are expounded in this paper, and derived from them are substantive conclusions for further studies, with the view to improving FMD immunoprophylaxis.", "contents": "[Current status of immunoprophylaxis against foot-and-mouth disease]. An analysis is made of the latest developments and importance of immunoprophylaxis against FMD, with reference to the epizootiological situation of the disease and its bearings, today, on industrialized livestock production. Comprehensive immunoprophylactic action (vaccination of all cattle every year) has been taken first by the GDR and later on by more European countries, as well. As a result of such action the disastrous impact of FMD and its associated high loss rate have been considerably mitigated. A decisive role, in that context, has been played by the development of effective inactivated vaccines for swine. An FMD live vaccine has been devised in GDR for after-care of swine. It is not only harmless to the animal, but, as well known, it provides numerous advantages over adsorbate vaccines. FMD immunoprophylaxis for full success depends primarily on the proper selection of virus strains suitable for vaccine produktion, vaccine quality, avoidance of post-vaccination damage or disease, and the availability of an efficient concept for vaccine application. The above problems are expounded in this paper, and derived from them are substantive conclusions for further studies, with the view to improving FMD immunoprophylaxis."}
{"id": "PMID:211979", "title": "[Results of veterinary tumor research and their significance for practice].", "content": "Enzootic bovine leucosis and Marek's disease of fowl are the most important tumour diseases of farm animals, with the greatest repercussions on the national economy, today. Experimental findings obtained from either disease in recent years are reported in this paper, and an assessment is made of their importance to practice. In the context of enzootic bovine leucosis, particular reference is made to those findings which helped to establish the presence of virus infection, results by which the pathogen could be characterised, and to studies undertaken with the view to devising methods for virologico-serological diagnosis. In the context of Marek's disease, reference is made to virological, epizootiological, and diagnostic aspects, however, with emphasis being laid on possibilities for immunisation and, in that connection, on known fundamental concepts for successful immunoprophylaxis against that tumour disease.", "contents": "[Results of veterinary tumor research and their significance for practice]. Enzootic bovine leucosis and Marek's disease of fowl are the most important tumour diseases of farm animals, with the greatest repercussions on the national economy, today. Experimental findings obtained from either disease in recent years are reported in this paper, and an assessment is made of their importance to practice. In the context of enzootic bovine leucosis, particular reference is made to those findings which helped to establish the presence of virus infection, results by which the pathogen could be characterised, and to studies undertaken with the view to devising methods for virologico-serological diagnosis. In the context of Marek's disease, reference is made to virological, epizootiological, and diagnostic aspects, however, with emphasis being laid on possibilities for immunisation and, in that connection, on known fundamental concepts for successful immunoprophylaxis against that tumour disease."}
{"id": "PMID:211981", "title": "[Transmissible gastroenteritis of swine as a model for infectious diarrhea].", "content": "Transmissible gastro-enteritis is a virus-caused diarrhoeal disease of swine which may result in up to a total loss among newborn animals. Changes are, primarily, of pathologicoanatomic nature and take place in the small intestine. The epithelium of the intestinal villi is completely destroyed, and diarrhoea is the result. Deformation in blood composition is a secondary sequel. The diarrhoea proper causes dehydration and acidosis which, in conjunction with abnormal heart function due to hyperkalaemia, cause death of the piglets affected. Reference is made to the intrinsic immunological conditions in swine, and possibilities are discussed for immunoprophylactic control of transmissible gastro-enteritis by induction of effective lactogenic immunity. The approaches taken to vaccine application should largely correspond to the natural route of infection.", "contents": "[Transmissible gastroenteritis of swine as a model for infectious diarrhea]. Transmissible gastro-enteritis is a virus-caused diarrhoeal disease of swine which may result in up to a total loss among newborn animals. Changes are, primarily, of pathologicoanatomic nature and take place in the small intestine. The epithelium of the intestinal villi is completely destroyed, and diarrhoea is the result. Deformation in blood composition is a secondary sequel. The diarrhoea proper causes dehydration and acidosis which, in conjunction with abnormal heart function due to hyperkalaemia, cause death of the piglets affected. Reference is made to the intrinsic immunological conditions in swine, and possibilities are discussed for immunoprophylactic control of transmissible gastro-enteritis by induction of effective lactogenic immunity. The approaches taken to vaccine application should largely correspond to the natural route of infection."}
{"id": "PMID:211983", "title": "Drug and family therapy in the aftercare of acute schizophrenics.", "content": "After a brief inpatient hospitalization, 104 acute, young schizophrenics, stratified by premorbid adjustment, were randomly assigned to one of four aftercare conditions for a six-week controlled trial. Conditions involved one of two dose levels of fluphenazine enanthate (1 ml or 0.25 ml) and presence or absence of crisis-oriented family therapy. Relapses during the six-week period and at six-month follow-up were least in patients who received both high-dose and family therapy (0%) and greatest (48%) in the low-dose-no therapy group. Brief Psychiatric Rating Scale symptom ratings disclosed a significant family therapy effect at six weeks that was sustained at six months only for therapy patients originally receiving the high drug dose. Numerous interactions were found between premorbid adjustment status and response to the two treatment conditions.", "contents": "Drug and family therapy in the aftercare of acute schizophrenics. After a brief inpatient hospitalization, 104 acute, young schizophrenics, stratified by premorbid adjustment, were randomly assigned to one of four aftercare conditions for a six-week controlled trial. Conditions involved one of two dose levels of fluphenazine enanthate (1 ml or 0.25 ml) and presence or absence of crisis-oriented family therapy. Relapses during the six-week period and at six-month follow-up were least in patients who received both high-dose and family therapy (0%) and greatest (48%) in the low-dose-no therapy group. Brief Psychiatric Rating Scale symptom ratings disclosed a significant family therapy effect at six weeks that was sustained at six months only for therapy patients originally receiving the high drug dose. Numerous interactions were found between premorbid adjustment status and response to the two treatment conditions."}
{"id": "PMID:211984", "title": "The effect of physostigmine on normal human sleep and dreaming.", "content": "Physostigmine, an anticholinesterase that increases the action of brain acetylcholine, induces rapid eye movement (REM) sleep in normal humans. In this study we show that man dreams during physostigmine-induced REM sleep. Seventeen normal volunteers were pretreated with methscopolamine and received one intravenous infusion per night of either placebo or physostigmine either ten or 35 minutes after sleep onset. Subjects were awakened at specific times after infusion and interviewed regarding any sleep mentation prior to awakening. Results indicated that dreaming occurred during physostigmine-induced REM periods but that physostigmine did not alter mentation during non-REM sleep. These dreams were similar to spontaneous REM sleep dreams in content, vividness, unusualness, and emotionality.", "contents": "The effect of physostigmine on normal human sleep and dreaming. Physostigmine, an anticholinesterase that increases the action of brain acetylcholine, induces rapid eye movement (REM) sleep in normal humans. In this study we show that man dreams during physostigmine-induced REM sleep. Seventeen normal volunteers were pretreated with methscopolamine and received one intravenous infusion per night of either placebo or physostigmine either ten or 35 minutes after sleep onset. Subjects were awakened at specific times after infusion and interviewed regarding any sleep mentation prior to awakening. Results indicated that dreaming occurred during physostigmine-induced REM periods but that physostigmine did not alter mentation during non-REM sleep. These dreams were similar to spontaneous REM sleep dreams in content, vividness, unusualness, and emotionality."}
{"id": "PMID:211985", "title": "Nocturnal sleep in separated monkey infants.", "content": "Nocturnal sleep was recorded from ten unrestrained, group-living Macaca nemestrina (pigtail) monkey infants, using implantable multichannel biotelemetry systems, during the agitation-depression behavioral reaction that follows maternal separation. Sleep disturbances during the four nights of separation were characterized by decreases in rapid eye movement (REM) time and in the number of REM periods, and increases in REM latency. Time awake and number of arousals were increased. Slow-wave sleep was not significantly affected. Sleep pattern changes were most pronounced the first separation night, and tended to decrease as separation continued, whereas behavioral measures of depression tended to increase as separation continued (up to four days). Sleep patterns returned to normal following reunion with the mother. Those infants who had the most severe sleep disturbances the first separation night (more time awake, less total sleep, less REM) also tended to become most depressed behaviorally later in the separation period.", "contents": "Nocturnal sleep in separated monkey infants. Nocturnal sleep was recorded from ten unrestrained, group-living Macaca nemestrina (pigtail) monkey infants, using implantable multichannel biotelemetry systems, during the agitation-depression behavioral reaction that follows maternal separation. Sleep disturbances during the four nights of separation were characterized by decreases in rapid eye movement (REM) time and in the number of REM periods, and increases in REM latency. Time awake and number of arousals were increased. Slow-wave sleep was not significantly affected. Sleep pattern changes were most pronounced the first separation night, and tended to decrease as separation continued, whereas behavioral measures of depression tended to increase as separation continued (up to four days). Sleep patterns returned to normal following reunion with the mother. Those infants who had the most severe sleep disturbances the first separation night (more time awake, less total sleep, less REM) also tended to become most depressed behaviorally later in the separation period."}
{"id": "PMID:211987", "title": "Murine leukemia virus in chemically-induced sarcomas as detected by XC plaque formation.", "content": "To detect whether methylcholanthrene induced murine sarcomas contain endogenous murine leukemia viruses, direct XC syncytium assays were performed over short term tumor cultures. Out of 31 sarcomas, 13 (42%) induced more than 4 plaques per flask, while no such activity was found in 39 control spleen samples. It is postulated that the positive tests are related to an increase in the titer of endogenous B-tropic virus, probably as a result rather than as a cause of tumor induction by chemicals.", "contents": "Murine leukemia virus in chemically-induced sarcomas as detected by XC plaque formation. To detect whether methylcholanthrene induced murine sarcomas contain endogenous murine leukemia viruses, direct XC syncytium assays were performed over short term tumor cultures. Out of 31 sarcomas, 13 (42%) induced more than 4 plaques per flask, while no such activity was found in 39 control spleen samples. It is postulated that the positive tests are related to an increase in the titer of endogenous B-tropic virus, probably as a result rather than as a cause of tumor induction by chemicals."}
{"id": "PMID:211986", "title": "Withdrawal from long-term high-dose desipramine therapy. Clinical and biological changes.", "content": "Investigation was undertaken on a patient whose long-term intake of desipramine hydrochloride was amongst the highest reported. Desipramine treatment instituted at a daily dosage of 75 mg for depressive equivalents of head, chest, and abdominal pain was increased to 1,000 mg daily over a 12-year interval with minimal side effects. Plasma desipramine level dropped immediately on withdrawal, and urinary metabolite values dropped over the subsequent five days. The electrocardiographic abnormalities of first-degree atrioventricular block and incomplete left bundle branch block rapidly disappeared on cessation of medication. Electroencephalographic changes with symmetrical generalized irregular 5- to 7-cps theta activity and 18- to 28-cps beta activity also improved. Longitudinal polygraphic sleep studies showed prolonged rapid eye movement rebound and increased delta sleep coincident with withdrawal. It took ten days after cessation of desipramine for urinary 3-methoxy-4-hydroxyphenylglycol concentration to increase substantially. Although catecholamines are involved in growth hormone (GH) and cortisol regulation, no abnormalities were found in GH or cortisol levels.", "contents": "Withdrawal from long-term high-dose desipramine therapy. Clinical and biological changes. Investigation was undertaken on a patient whose long-term intake of desipramine hydrochloride was amongst the highest reported. Desipramine treatment instituted at a daily dosage of 75 mg for depressive equivalents of head, chest, and abdominal pain was increased to 1,000 mg daily over a 12-year interval with minimal side effects. Plasma desipramine level dropped immediately on withdrawal, and urinary metabolite values dropped over the subsequent five days. The electrocardiographic abnormalities of first-degree atrioventricular block and incomplete left bundle branch block rapidly disappeared on cessation of medication. Electroencephalographic changes with symmetrical generalized irregular 5- to 7-cps theta activity and 18- to 28-cps beta activity also improved. Longitudinal polygraphic sleep studies showed prolonged rapid eye movement rebound and increased delta sleep coincident with withdrawal. It took ten days after cessation of desipramine for urinary 3-methoxy-4-hydroxyphenylglycol concentration to increase substantially. Although catecholamines are involved in growth hormone (GH) and cortisol regulation, no abnormalities were found in GH or cortisol levels."}
{"id": "PMID:211989", "title": "In vitro growth characteristics and heterogeneity of mouse hepatitis virus type 3.", "content": "The in vitro virus yield of MHV3 reached 10(7) PFU/ml in mouse DBT cells infected with a virus suspension in HEPES-buffered medium containing DEAE-dextran. The virus titer was 10(6) PFU/ml in the presence of 10 micrograms actinomycin D/ml MHV3 growth in DBT cells gave three peaks of density (1.10--1.14 g/cm3, 1.18--1.20 g/cm3, and 1.25--1.31 g/cm3) in sucrose gradients. All these peaks retained infectivity.", "contents": "In vitro growth characteristics and heterogeneity of mouse hepatitis virus type 3. The in vitro virus yield of MHV3 reached 10(7) PFU/ml in mouse DBT cells infected with a virus suspension in HEPES-buffered medium containing DEAE-dextran. The virus titer was 10(6) PFU/ml in the presence of 10 micrograms actinomycin D/ml MHV3 growth in DBT cells gave three peaks of density (1.10--1.14 g/cm3, 1.18--1.20 g/cm3, and 1.25--1.31 g/cm3) in sucrose gradients. All these peaks retained infectivity."}
{"id": "PMID:211990", "title": "Differentiation between specific and nonspecific reactions of bovine sera and foot and mouth disease virus (FMDV) in immunodiffusion tests.", "content": "The precipitating and neutralizing activities of normal bovine sera with FMDV were studied and compared. Twenty-two out of 79 normal bovine sera gave a positive reaction in micro neutralization tests with FMDV type O, while six did so with type A. In RID tests 32 sera were positive with type O and 28 with type A virus. Almost all of the 79 sera gave a positive reaction in the RID with trypsin treated virus of both types. After three to four fold concentration most sera also gave visible reactions in ID tests when tested against complete virus. When O virus was used the ID patterns produced by most normal sera clearly differed from those obtained with early and late convalescent sera from FMDV infected steers. When type A materials were employed this was also the case but to a lesser extent. The patterns obtained with concentrated normal sera showed, in general a strong line with trypsin treated virus and no line or a weaker one with complete virus. The substances in normal bovine sera precipitating trypsin treated O virus were different from those reacting with trypsinized virus of type A.", "contents": "Differentiation between specific and nonspecific reactions of bovine sera and foot and mouth disease virus (FMDV) in immunodiffusion tests. The precipitating and neutralizing activities of normal bovine sera with FMDV were studied and compared. Twenty-two out of 79 normal bovine sera gave a positive reaction in micro neutralization tests with FMDV type O, while six did so with type A. In RID tests 32 sera were positive with type O and 28 with type A virus. Almost all of the 79 sera gave a positive reaction in the RID with trypsin treated virus of both types. After three to four fold concentration most sera also gave visible reactions in ID tests when tested against complete virus. When O virus was used the ID patterns produced by most normal sera clearly differed from those obtained with early and late convalescent sera from FMDV infected steers. When type A materials were employed this was also the case but to a lesser extent. The patterns obtained with concentrated normal sera showed, in general a strong line with trypsin treated virus and no line or a weaker one with complete virus. The substances in normal bovine sera precipitating trypsin treated O virus were different from those reacting with trypsinized virus of type A."}
{"id": "PMID:211991", "title": "Polyethylene glycol-mediated infection with avian sarcoma viruses.", "content": "In this communication we report that fusion of viral and cellular membranes by polyethylene glycol is a convenient approach to overcoming genetically determined resistance to infection. Using this method, avian sarcoma virus-transformed mammalian cells have been produced which serve as useful model systems for the study of Rous sarcoma virus-specific tumor antigens.", "contents": "Polyethylene glycol-mediated infection with avian sarcoma viruses. In this communication we report that fusion of viral and cellular membranes by polyethylene glycol is a convenient approach to overcoming genetically determined resistance to infection. Using this method, avian sarcoma virus-transformed mammalian cells have been produced which serve as useful model systems for the study of Rous sarcoma virus-specific tumor antigens."}
{"id": "PMID:211992", "title": "The structure of the Rous sarcoma virus glycoprotein complex.", "content": "The viral envelope glycoprotein gp85 is released from purified Rous sarcoma virus by treatment with 2-mercaptoethanol, while the second surface antigen gp35 remains associated with the membrane of intact virus particles. The data represented substantiate and extend previous observations on the Rous sarcoma virus glycoprotein complex.", "contents": "The structure of the Rous sarcoma virus glycoprotein complex. The viral envelope glycoprotein gp85 is released from purified Rous sarcoma virus by treatment with 2-mercaptoethanol, while the second surface antigen gp35 remains associated with the membrane of intact virus particles. The data represented substantiate and extend previous observations on the Rous sarcoma virus glycoprotein complex."}
{"id": "PMID:211993", "title": "In vitro RNA synthesis in nuclei from herpes simplex virus infected cells: effects of ultraviolet-irradiated, defective and bromodeoxyuridine-resistant virus preparations.", "content": "Transcription of virus DNA was detectable in vitro in nuclei isolated from cells infected with wild type and bromodeoxyuridine (BUdR)-resistant herpes simplex virus type 1 but was suppressed in nuclei of cells infected with ultraviolet irradiated or defective virus or cells treated with BUdR during infection.", "contents": "In vitro RNA synthesis in nuclei from herpes simplex virus infected cells: effects of ultraviolet-irradiated, defective and bromodeoxyuridine-resistant virus preparations. Transcription of virus DNA was detectable in vitro in nuclei isolated from cells infected with wild type and bromodeoxyuridine (BUdR)-resistant herpes simplex virus type 1 but was suppressed in nuclei of cells infected with ultraviolet irradiated or defective virus or cells treated with BUdR during infection."}
{"id": "PMID:211994", "title": "Various heterologous cells exhibit interferon induced transfer of viral resistance.", "content": "Previously it was shown that cocultivation of mouse L and human WISH or baby hamster kidney cells in the presence of mouse interferon resulted in decreased viral yield from both cell species. We now show that this phenomenon also occurs when rabbit kidney and human WISH cells, with their corresponding interferons, are cocultivated with human WISH and baby hamster kidney cells, respectively. This finding increases the number of donor cell types to three. The related finding that monkey VERO and chick embryo cells can be recipients of transferred resistance expands the number of heterologous recipient cell species capable of receiving transferred resistence to five. Not all cell types tested have been shown to function in this transfer system. The fact that VERO cells, which do not produce interferon, are capable of receiving transferred resistence is significant because it indicates that the mechanism of transfer does not involve production or interferon by the recipient cells.", "contents": "Various heterologous cells exhibit interferon induced transfer of viral resistance. Previously it was shown that cocultivation of mouse L and human WISH or baby hamster kidney cells in the presence of mouse interferon resulted in decreased viral yield from both cell species. We now show that this phenomenon also occurs when rabbit kidney and human WISH cells, with their corresponding interferons, are cocultivated with human WISH and baby hamster kidney cells, respectively. This finding increases the number of donor cell types to three. The related finding that monkey VERO and chick embryo cells can be recipients of transferred resistance expands the number of heterologous recipient cell species capable of receiving transferred resistence to five. Not all cell types tested have been shown to function in this transfer system. The fact that VERO cells, which do not produce interferon, are capable of receiving transferred resistence is significant because it indicates that the mechanism of transfer does not involve production or interferon by the recipient cells."}
{"id": "PMID:211996", "title": "Disulfiram neuropathy.", "content": "A 35-year-old man developed a distal sensorimotor polyneuropathy after taking disulfiram, 500 mg daily for five months. His symptoms improved after the drug therapy was discontinued. Clinical, electrophysiological, and pathological observations during the acute stage and during recovery suggest that disulfiram produces a distal axonopathy.", "contents": "Disulfiram neuropathy. A 35-year-old man developed a distal sensorimotor polyneuropathy after taking disulfiram, 500 mg daily for five months. His symptoms improved after the drug therapy was discontinued. Clinical, electrophysiological, and pathological observations during the acute stage and during recovery suggest that disulfiram produces a distal axonopathy."}
{"id": "PMID:211997", "title": "Herpes simplex virus subunit antibodies in patients with Parkinson's disease.", "content": "Serum IgG antibodies against herpes simplex virus (HSV) type 1 capsid, envelope, and excreted antigens in 52 patients with idiopathic Parkinson's disease, and in their age- and sex-matched controls, were assayed with a solid-phase radioimmunoassay. When compared with the controls, patients with Parkinson's disease were found to have a substantially increased antibody response against each of the HSV subunit antigens tested. The increased antibody response in patients with Parkinson's disease was not associated with the occurrence of recurrent HSV infections, since the difference in antibody levels was most evident when comparing patients without recurrent HSV infections with their respective control group. Consequently, the increased HSV antibody response in patient with Parkinson's disease might depend on some antigenic stimulation other than ordinary recurrent HSV infections, or alternatively, on the generally enhanced immunological reaction of the patients against HSV.", "contents": "Herpes simplex virus subunit antibodies in patients with Parkinson's disease. Serum IgG antibodies against herpes simplex virus (HSV) type 1 capsid, envelope, and excreted antigens in 52 patients with idiopathic Parkinson's disease, and in their age- and sex-matched controls, were assayed with a solid-phase radioimmunoassay. When compared with the controls, patients with Parkinson's disease were found to have a substantially increased antibody response against each of the HSV subunit antigens tested. The increased antibody response in patients with Parkinson's disease was not associated with the occurrence of recurrent HSV infections, since the difference in antibody levels was most evident when comparing patients without recurrent HSV infections with their respective control group. Consequently, the increased HSV antibody response in patient with Parkinson's disease might depend on some antigenic stimulation other than ordinary recurrent HSV infections, or alternatively, on the generally enhanced immunological reaction of the patients against HSV."}
{"id": "PMID:211998", "title": "Serum pyridoxal concentrations in patients with diabetic neuropathy.", "content": "Serum pyridoxal (vitamin B6) concentrations were measured in 50 patients with significant diabetic neuropathy. There were 24 males and 26 females with a mean age of 58.2 years and a mean duration of diabetes of 9.8 years. The level of pyridoxal was significantly lower in these patients when compared with randomly selected diabetic patients matched for age and sex without clinical evidence of neuropathy. There was no significant difference in the duration of the diabetes between the two groups. The results indicate an association between pyridoxal deficiency and neuropathy in diabetic patients.", "contents": "Serum pyridoxal concentrations in patients with diabetic neuropathy. Serum pyridoxal (vitamin B6) concentrations were measured in 50 patients with significant diabetic neuropathy. There were 24 males and 26 females with a mean age of 58.2 years and a mean duration of diabetes of 9.8 years. The level of pyridoxal was significantly lower in these patients when compared with randomly selected diabetic patients matched for age and sex without clinical evidence of neuropathy. There was no significant difference in the duration of the diabetes between the two groups. The results indicate an association between pyridoxal deficiency and neuropathy in diabetic patients."}
{"id": "PMID:211999", "title": "Duration of vaccinal immunity against Marek's disease.", "content": "Specific vaccinal immunity against Marek's disease (MD) virus was measured by a short-term challenge test in which chickens vaccinated with turkey herpesvirus (HVT) and control chickens at various ages up to 40 weeks were inoculated with virulent MD virus and evaluated 2 weeks later for microscopic lesions and MD viremia. Vaccinal immunity induced by high (2,900 PFU) and low (29 PFU) doses of HVT persisted without detectable reduction through the 40th week in line 151 chickens, thus indicating that resistance of older vaccinated chickens to MD may not be based solely on general age resistance (immunocompetence) or on subsequent exposure to field MD virus. The HVT viremia titers (number of buffy-coat cells inducing virus plaques in vitro) decreased with increasing age, but even chickens from which no HVT was isolated were usually immune to MD. The dose of vaccine appeared to influence, at least slightly, the magnitude of MD immunity and vaccine virus viremia.", "contents": "Duration of vaccinal immunity against Marek's disease. Specific vaccinal immunity against Marek's disease (MD) virus was measured by a short-term challenge test in which chickens vaccinated with turkey herpesvirus (HVT) and control chickens at various ages up to 40 weeks were inoculated with virulent MD virus and evaluated 2 weeks later for microscopic lesions and MD viremia. Vaccinal immunity induced by high (2,900 PFU) and low (29 PFU) doses of HVT persisted without detectable reduction through the 40th week in line 151 chickens, thus indicating that resistance of older vaccinated chickens to MD may not be based solely on general age resistance (immunocompetence) or on subsequent exposure to field MD virus. The HVT viremia titers (number of buffy-coat cells inducing virus plaques in vitro) decreased with increasing age, but even chickens from which no HVT was isolated were usually immune to MD. The dose of vaccine appeared to influence, at least slightly, the magnitude of MD immunity and vaccine virus viremia."}
{"id": "PMID:212000", "title": "Lymphoproliferative diseases of fowl: characterization of transplantable G-B1 Marek's disease tumor cells in culture.", "content": "A transplantable Marek's disease tumor, derived and maintained through in vivo passage in syngeneic G-B1 chickens, was established in cell culture and characterized. The cells (GBT cells) grew in suspension and appeared morphologically similar to other Marek's lymphoblastoid lines except for prominent nucleoli in GBT cells. The number of chromosomes increased during in vitro cultivation from near triploid to subtetraploid. Chromosome no. 3 was abnormally short. The GBT cells retained surface B1 histocompatibility antigen of the original tumor as well as Marek's disease tumor-specific surface antigen (MATSA); however, infectious Marek's disease virus was not detected by immunofluorescence, electron microscopy, inoculation into susceptible birds, or assay on susceptible cells in culture. Inoculation of as few as 100 cultured cells into syngeneic G-B1 chickens results in tumor formation at the inoculation site, with eventual death of the recipients.", "contents": "Lymphoproliferative diseases of fowl: characterization of transplantable G-B1 Marek's disease tumor cells in culture. A transplantable Marek's disease tumor, derived and maintained through in vivo passage in syngeneic G-B1 chickens, was established in cell culture and characterized. The cells (GBT cells) grew in suspension and appeared morphologically similar to other Marek's lymphoblastoid lines except for prominent nucleoli in GBT cells. The number of chromosomes increased during in vitro cultivation from near triploid to subtetraploid. Chromosome no. 3 was abnormally short. The GBT cells retained surface B1 histocompatibility antigen of the original tumor as well as Marek's disease tumor-specific surface antigen (MATSA); however, infectious Marek's disease virus was not detected by immunofluorescence, electron microscopy, inoculation into susceptible birds, or assay on susceptible cells in culture. Inoculation of as few as 100 cultured cells into syngeneic G-B1 chickens results in tumor formation at the inoculation site, with eventual death of the recipients."}
{"id": "PMID:212002", "title": "Differentiation of avian infectious bronchitis virus isolates by thermal sensitivity.", "content": "Six isolates of avian infectious bronchitis virus (IBV) at different passage levels in the chicken embryo were tested for sensitivity at 56 C, with the following results: 1) isolates differed in thermal sensitivity; 2) virus was inactivated in a first-order exponential-kinetics 2-component fashion indicative of a heterogeneous population with a preponderance, 98% or more, of thermal-sensitive (S) virions over thermal-resistant (R) virons; 3) R virions 2-component populations were inactivated; 4) recovered R virions could be maintained in continuous passage in the chicken embryo as a one-component population by the limiting-dilution technique, although there was a progressive parallel increase in thermal sensitivity associated directly with the continuous passage; 5) growth curves of isolated one-component populations of R virions were quantitatively and in time sequence similar to curves of 2-component populations of continuous-passage virus.", "contents": "Differentiation of avian infectious bronchitis virus isolates by thermal sensitivity. Six isolates of avian infectious bronchitis virus (IBV) at different passage levels in the chicken embryo were tested for sensitivity at 56 C, with the following results: 1) isolates differed in thermal sensitivity; 2) virus was inactivated in a first-order exponential-kinetics 2-component fashion indicative of a heterogeneous population with a preponderance, 98% or more, of thermal-sensitive (S) virions over thermal-resistant (R) virons; 3) R virions 2-component populations were inactivated; 4) recovered R virions could be maintained in continuous passage in the chicken embryo as a one-component population by the limiting-dilution technique, although there was a progressive parallel increase in thermal sensitivity associated directly with the continuous passage; 5) growth curves of isolated one-component populations of R virions were quantitatively and in time sequence similar to curves of 2-component populations of continuous-passage virus."}
{"id": "PMID:212001", "title": "Interaction of aflatoxin with infectious bursal disease virus infection in young chickens.", "content": "Young White Leghorn chickens fed 2.5 microgram of aflatoxin (Afl) per g of diet from hatching until 4 weeks old and infected with infectious bursal disease virus (IBDV) at 3 weeks old had significantly higher mortality and more severely depressed body weights than chicks with aflatoxicosis or IBD alone. Afl-IBDV chicks also had more extensive gross and microscopic changes characteristic of IBD than did IBDV-chicks. None of the treatments significantly reduced antibody responses to Newcastle disease(ND) and infectious bronchitis vaccines or increased susceptibility to challenge with virulent NDV. In a similar experiment chickens fed Afl from hatching to 7 weeks of age had no marked depression in immune response to ND vaccination.", "contents": "Interaction of aflatoxin with infectious bursal disease virus infection in young chickens. Young White Leghorn chickens fed 2.5 microgram of aflatoxin (Afl) per g of diet from hatching until 4 weeks old and infected with infectious bursal disease virus (IBDV) at 3 weeks old had significantly higher mortality and more severely depressed body weights than chicks with aflatoxicosis or IBD alone. Afl-IBDV chicks also had more extensive gross and microscopic changes characteristic of IBD than did IBDV-chicks. None of the treatments significantly reduced antibody responses to Newcastle disease(ND) and infectious bronchitis vaccines or increased susceptibility to challenge with virulent NDV. In a similar experiment chickens fed Afl from hatching to 7 weeks of age had no marked depression in immune response to ND vaccination."}
{"id": "PMID:212003", "title": "Experimental infection of turkeys with infectious bursal disease virus.", "content": "Commercial turkey poults 3 to 6 weeks old were infected experimentally by eyedrop with an infectious bursal disease virus (IBDV) inoculum obtained from chickens experiencing clinical IBD. The IBDV was passed 6 successive times in poults in an attempt to increase its pathogenicity for turkeys. Regardless of passage level, the IBDV infection in poults was subclinical, with no morbidity, mortality, or gross lesions observed. The bursae of Fabricius from infected poults, however, displayed various degrees of microscopic degeneration and IBDV specific fluorescence at 3, 4, and 5 days postinfection (PI). Infected turkeys also developed low levels of virus-neutralizing antibodies against IBDV at 12 days PI. Uninoculated poults kept in the same unit with infected poults also displayed microscopic changes and IBDV specific fluorescence 7 days after their appearance in inoculated poults. The IBDV was isolated from infected poults only after 5 successive passages of bursal material from infected poults in 9-day-old chick embryos. The IBDV from infected embryos was inoculated into susceptible 3-week-old chickens and 5-week-old poults and produced IBDV fluorescence and microscopic pathology in the bursae of infected poults and clinical IBD in infected chickens.", "contents": "Experimental infection of turkeys with infectious bursal disease virus. Commercial turkey poults 3 to 6 weeks old were infected experimentally by eyedrop with an infectious bursal disease virus (IBDV) inoculum obtained from chickens experiencing clinical IBD. The IBDV was passed 6 successive times in poults in an attempt to increase its pathogenicity for turkeys. Regardless of passage level, the IBDV infection in poults was subclinical, with no morbidity, mortality, or gross lesions observed. The bursae of Fabricius from infected poults, however, displayed various degrees of microscopic degeneration and IBDV specific fluorescence at 3, 4, and 5 days postinfection (PI). Infected turkeys also developed low levels of virus-neutralizing antibodies against IBDV at 12 days PI. Uninoculated poults kept in the same unit with infected poults also displayed microscopic changes and IBDV specific fluorescence 7 days after their appearance in inoculated poults. The IBDV was isolated from infected poults only after 5 successive passages of bursal material from infected poults in 9-day-old chick embryos. The IBDV from infected embryos was inoculated into susceptible 3-week-old chickens and 5-week-old poults and produced IBDV fluorescence and microscopic pathology in the bursae of infected poults and clinical IBD in infected chickens."}
{"id": "PMID:212005", "title": "Purification of avian encephalomyelitis virus by ultracentrifugation in a nonlinear cesium chloride gradient.", "content": "A rapid and convenient method is described for purifying avian encephalomyelitis virus. Infected embryo homogenate was treated with polyethylene glycol followed by extraction with fluorocarbon. Extracted sample was pelleted at 73,400 x g, resuspended, and subjected to isodensity centrifugation in preformed nonlinear gradient. A distinctive virus band was observed after centrifugation for 120 min at 192,000 x g. The fraction containing the virus band demonstrated the major portion of infectivity and the presence of the virus particles by electron microscopy. The method was reproducible within a limited number of trials.", "contents": "Purification of avian encephalomyelitis virus by ultracentrifugation in a nonlinear cesium chloride gradient. A rapid and convenient method is described for purifying avian encephalomyelitis virus. Infected embryo homogenate was treated with polyethylene glycol followed by extraction with fluorocarbon. Extracted sample was pelleted at 73,400 x g, resuspended, and subjected to isodensity centrifugation in preformed nonlinear gradient. A distinctive virus band was observed after centrifugation for 120 min at 192,000 x g. The fraction containing the virus band demonstrated the major portion of infectivity and the presence of the virus particles by electron microscopy. The method was reproducible within a limited number of trials."}
{"id": "PMID:212004", "title": "Avian adenoviruses: effect on egg production, shell quality, and feed consumption.", "content": "Four avian adenovirus isolants (Indiana C, DPI-2, IBH-2, and B-3)were examined for pathogenicity in laying birds. None affected shell quality, and only one (IBH-2) had even a minimal effect on egg production (faster decline). Of three isolants tested (Indiana C, DPI-2, and IBH-2), only IBH-2 caused feed intake to be reduced. No other clinical signs were observed during these experiments. Egg transmission, virus excretion, and antibody production were found to mimic patterns reported for serotype-1 avian adenoviruses.", "contents": "Avian adenoviruses: effect on egg production, shell quality, and feed consumption. Four avian adenovirus isolants (Indiana C, DPI-2, IBH-2, and B-3)were examined for pathogenicity in laying birds. None affected shell quality, and only one (IBH-2) had even a minimal effect on egg production (faster decline). Of three isolants tested (Indiana C, DPI-2, and IBH-2), only IBH-2 caused feed intake to be reduced. No other clinical signs were observed during these experiments. Egg transmission, virus excretion, and antibody production were found to mimic patterns reported for serotype-1 avian adenoviruses."}
{"id": "PMID:212006", "title": "Rhinotracheitis in turkey poults.", "content": "A severe upper respiratory disease of young turkeys is described that resulted in high morbidity and mortality. Death was due to asphyxiation produced by occlusion of the trachea or nostrils. The postmortem lesions were tracheitis, pulmonary edema, swollen livers and spleens, and a drastic reduction in bursa size. Bursal necrosis and loss of tracheal epithelium were found in tissue sections from clinically affected birds. Antibody to infectious bursal disease was found by agar-gel precipitin and virus-neutralization tests of serum samples from affected flocks. A geometric mean titer of 31.5 for Newcastle disease was found in unvaccinated flocks of five-week-old turkeys.", "contents": "Rhinotracheitis in turkey poults. A severe upper respiratory disease of young turkeys is described that resulted in high morbidity and mortality. Death was due to asphyxiation produced by occlusion of the trachea or nostrils. The postmortem lesions were tracheitis, pulmonary edema, swollen livers and spleens, and a drastic reduction in bursa size. Bursal necrosis and loss of tracheal epithelium were found in tissue sections from clinically affected birds. Antibody to infectious bursal disease was found by agar-gel precipitin and virus-neutralization tests of serum samples from affected flocks. A geometric mean titer of 31.5 for Newcastle disease was found in unvaccinated flocks of five-week-old turkeys."}
{"id": "PMID:212012", "title": "Oxidation-reduction studies of the Mo-(2Fe-2S) protein from Desulfovibrio gigas.", "content": "Potentiometric titration followed by e.p.r. measurements were used to determine the midpoint reduction potentials of the redox centres of a molybdenum-containing iron-sulphur protein previously isolated from Desulfovibrio gigas, a sulphate-reducing bacterium (Moura, Xavier, Bruschi, Le Gall, Hall & Cammack (1976) Biochem. Biophys. Res. Commun. 728 782-789; Moura, Xavier, Bruschi, Le Gall & Cabral (1977) J. Less Common Metals 54, 555-562). The iron-sulphur centres could readily be distinguished into three types by means of g values, temperature effect, oxidation-reduction potential values and reduction rates. The type-I Fe-S centres are observed at 77 K. They show mid-point potential values of -260mV (Fe-S type IA) and -440 mV (Fe-S type IB). Centres of types IA and IB appear to have similar spectra at 77 K and 24 K. The Fe-S type-II centres are only observed below 65 K and have a midpoint potential of -28mV. Long equilibration times (30 min) with dye mediators under reducing conditions were necessary to observe the very slow equilibrating molybdenum signals. The potential values associated with this signal were estimated to be approx. -415 mV for Mo(VI)/Mo(V) and-530mV for Mo(V)/Mo(IV).", "contents": "Oxidation-reduction studies of the Mo-(2Fe-2S) protein from Desulfovibrio gigas. Potentiometric titration followed by e.p.r. measurements were used to determine the midpoint reduction potentials of the redox centres of a molybdenum-containing iron-sulphur protein previously isolated from Desulfovibrio gigas, a sulphate-reducing bacterium (Moura, Xavier, Bruschi, Le Gall, Hall & Cammack (1976) Biochem. Biophys. Res. Commun. 728 782-789; Moura, Xavier, Bruschi, Le Gall & Cabral (1977) J. Less Common Metals 54, 555-562). The iron-sulphur centres could readily be distinguished into three types by means of g values, temperature effect, oxidation-reduction potential values and reduction rates. The type-I Fe-S centres are observed at 77 K. They show mid-point potential values of -260mV (Fe-S type IA) and -440 mV (Fe-S type IB). Centres of types IA and IB appear to have similar spectra at 77 K and 24 K. The Fe-S type-II centres are only observed below 65 K and have a midpoint potential of -28mV. Long equilibration times (30 min) with dye mediators under reducing conditions were necessary to observe the very slow equilibrating molybdenum signals. The potential values associated with this signal were estimated to be approx. -415 mV for Mo(VI)/Mo(V) and-530mV for Mo(V)/Mo(IV)."}
{"id": "PMID:212013", "title": "Evidence for an essential arginine recognition site on adenosine 3':5'-cyclic monophosphate-dependent protein kinase of rabbit skeletal muscle.", "content": "On the basis of the chemical and structural features of the amino acid sequences in the vicinities of phosphorylatable hydroxyamino acid residues in several of the well-known protein substrates for skeletal-muscle cyclic AMP-dependent protein kinase, it is hypothesized that the phosphorylatable residue at position i and arginine residue at position i-3 of these protein substrates are located on a peptide turn on the hydrophilic protein surface. It is further hypothesized that there is an arginine-recognition site near the active centre on the protein kinase. This site is essential for the function of cyclic AMP-dependent protein kinase, for, not only does it recognize specifically the exposed arginine residue of the protein substrate, but, more importantly, via the interaction with arginine-(i--3), it may help to steer the topologically adjacent serine-i into proper orientation on the nearby active centre for phosphorylation. Model-building and kinetic data that provide support for the proposed hypotheses are presented.", "contents": "Evidence for an essential arginine recognition site on adenosine 3':5'-cyclic monophosphate-dependent protein kinase of rabbit skeletal muscle. On the basis of the chemical and structural features of the amino acid sequences in the vicinities of phosphorylatable hydroxyamino acid residues in several of the well-known protein substrates for skeletal-muscle cyclic AMP-dependent protein kinase, it is hypothesized that the phosphorylatable residue at position i and arginine residue at position i-3 of these protein substrates are located on a peptide turn on the hydrophilic protein surface. It is further hypothesized that there is an arginine-recognition site near the active centre on the protein kinase. This site is essential for the function of cyclic AMP-dependent protein kinase, for, not only does it recognize specifically the exposed arginine residue of the protein substrate, but, more importantly, via the interaction with arginine-(i--3), it may help to steer the topologically adjacent serine-i into proper orientation on the nearby active centre for phosphorylation. Model-building and kinetic data that provide support for the proposed hypotheses are presented."}
{"id": "PMID:212014", "title": "rac-Glycerol 1:2-cyclic phosphate 2-phosphodiesterase, a new soluble phosphodiesterase of mammalian tissues.", "content": "1. A soluble phosphodiesterase is present in mammalian tissues which rapidly hydrolyses enantiomorphs of rac-glycerol 1:2-cyclic phosphate, producing rac-glycerol 1-phosphate. 2. The enzyme has been purified up to 1700-fold by a combination of acetone precipitation and chromatography on DEAE-Sephadex A-50, Sephadex G-150 and hydroxyapatite. 3. The Km with glycerol cyclic phosphate as substrate is 7.2 mM, and the pH optimum broad (6.9--7.5). The molecular weight (by gel filtration) of the enzyme is approx. 35500. 4. The phosphodiesterase has no requirement for Ca2+ or Mg2+, but is stimulated by reducing agents (cysteine, dithiothreitol) and Fe2+. 5. The purified phosphodiesterase preparation also hydrolysed 3':5'-cyclic AMP, producing 5'-AMP exclusively, and 2':3'-cyclic AMP, forming 3'-AMP and 2'-AMP in the ratio 7:3. Bis-(p-nitrophenyl) phosphate was slowly hydrolysed, but other phosphodiesters tested were not attacked. 6. The phosphodiesterase is inhibited by theophylline and o-phenanthroline. It is inhibited by Pi and by a variety of phosphomonoesters, of which certain aromatic primary phosphates are particularly effective.", "contents": "rac-Glycerol 1:2-cyclic phosphate 2-phosphodiesterase, a new soluble phosphodiesterase of mammalian tissues. 1. A soluble phosphodiesterase is present in mammalian tissues which rapidly hydrolyses enantiomorphs of rac-glycerol 1:2-cyclic phosphate, producing rac-glycerol 1-phosphate. 2. The enzyme has been purified up to 1700-fold by a combination of acetone precipitation and chromatography on DEAE-Sephadex A-50, Sephadex G-150 and hydroxyapatite. 3. The Km with glycerol cyclic phosphate as substrate is 7.2 mM, and the pH optimum broad (6.9--7.5). The molecular weight (by gel filtration) of the enzyme is approx. 35500. 4. The phosphodiesterase has no requirement for Ca2+ or Mg2+, but is stimulated by reducing agents (cysteine, dithiothreitol) and Fe2+. 5. The purified phosphodiesterase preparation also hydrolysed 3':5'-cyclic AMP, producing 5'-AMP exclusively, and 2':3'-cyclic AMP, forming 3'-AMP and 2'-AMP in the ratio 7:3. Bis-(p-nitrophenyl) phosphate was slowly hydrolysed, but other phosphodiesters tested were not attacked. 6. The phosphodiesterase is inhibited by theophylline and o-phenanthroline. It is inhibited by Pi and by a variety of phosphomonoesters, of which certain aromatic primary phosphates are particularly effective."}
{"id": "PMID:212015", "title": "Purification and properties of retinoic acid-binding protein from chick-embryo skin.", "content": "Retinoic acid-binding protein, which is considered to mediate the biological function of retinoic acid in epithelial differentiation and in the possible control of tumorigenesis, was reproducibly purified from chick-embryo skin by using DEAE-Sephadex and Sephadex G-100 column chromatography and isoelectric focusing. About 1mg of protein was isolated from 60g of skin. The purified protein-ligand complex was found to be homogeneous by electrophoresis on polyacrylamide gels. The binding protein has mol.wt. 17800 and pI 4.5. The binding of [3H]retinoic acid to the protein was completely inhibited by mercury compounds. The inhibition is reversible on treatment without dithithreitol; about 50% of the retinoic acid-binding capacity of the mercury-compound-treated protein is restored by chromatography on Sephadex G-25. iodoacetamide treatment of the protein irreversibly inhibits about 50% of retinoic acid binding.", "contents": "Purification and properties of retinoic acid-binding protein from chick-embryo skin. Retinoic acid-binding protein, which is considered to mediate the biological function of retinoic acid in epithelial differentiation and in the possible control of tumorigenesis, was reproducibly purified from chick-embryo skin by using DEAE-Sephadex and Sephadex G-100 column chromatography and isoelectric focusing. About 1mg of protein was isolated from 60g of skin. The purified protein-ligand complex was found to be homogeneous by electrophoresis on polyacrylamide gels. The binding protein has mol.wt. 17800 and pI 4.5. The binding of [3H]retinoic acid to the protein was completely inhibited by mercury compounds. The inhibition is reversible on treatment without dithithreitol; about 50% of the retinoic acid-binding capacity of the mercury-compound-treated protein is restored by chromatography on Sephadex G-25. iodoacetamide treatment of the protein irreversibly inhibits about 50% of retinoic acid binding."}
{"id": "PMID:212016", "title": "Conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active complex by the phosphate reaction in heart mitochondria is inhibited by alloxan-diabetes or starvation in the rat.", "content": "1. The conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active (dephosphorylated) complex by pyruvate dehydrogenase phosphate phosphatase is inhibited in heart mitochondria prepared from alloxan-diabetic or 48h-starved rats, in mitochondria prepared from acetate-perfused rat hearts and in mitochondria prepared from normal rat hearts incubated with respiratory substrates for 6 min (as compared with 1 min). 2. This conclusion is based on experiments with isolated intact mitochondria in which the pyruvate dehydrogenase kinase reaction was inhibited by pyruvate or ATP depletion (by using oligomycin and carbonyl cyanide m-chlorophenylhydrazone), and in experiments in which the rate of conversion of inactive complex into active complex by the phosphatase was measured in extracts of mitochondria. The inhibition of the phosphatase reaction was seen with constant concentrations of Ca2+ and Mg2+ (activators of the phosphatase). The phosphatase reaction in these mitochondrial extracts was not inhibited when an excess of exogenous pig heart pyruvate dehydrogenase phosphate was used as substrate. It is concluded that this inhibition is due to some factor(s) associated with the substrate (pyruvate dehydrogenase phosphate complex) and not to inhibition of the phosphatase as such. 3. This conclusion was verified by isolating pyruvate dehydrogenase phosphate complex, free of phosphatase, from hearts of control and diabetic rats an from heart mitochondria incubed for 1min (control) or 6min with respiratory substrates. The rates of re-activation of the inactive complexes were then measured with preparations of ox heart or rat heart phosphatase. The rates were lower (relative to controls) with inactive complex from hearts of diabetic rats or from heart mitochondria incubated for 6min with respiratory substrates. 4. The incorporation of 32Pi into inactive complex took 6min to complete in rat heart mitocondria. The extent of incorporation was consistent with three or four sites of phosphorylation in rat heart pyruvate dehydrogenase complex. 5. It is suggested that phosphorylation of sites additional to an inactivating site may inhibit the conversion of inactive complex into active complex by the phosphatase in heart mitochondria from alloxan-diabetic or 48h-starved rats or in mitochondria incubated for 6min with respiratory substrates.", "contents": "Conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active complex by the phosphate reaction in heart mitochondria is inhibited by alloxan-diabetes or starvation in the rat. 1. The conversion of inactive (phosphorylated) pyruvate dehydrogenase complex into active (dephosphorylated) complex by pyruvate dehydrogenase phosphate phosphatase is inhibited in heart mitochondria prepared from alloxan-diabetic or 48h-starved rats, in mitochondria prepared from acetate-perfused rat hearts and in mitochondria prepared from normal rat hearts incubated with respiratory substrates for 6 min (as compared with 1 min). 2. This conclusion is based on experiments with isolated intact mitochondria in which the pyruvate dehydrogenase kinase reaction was inhibited by pyruvate or ATP depletion (by using oligomycin and carbonyl cyanide m-chlorophenylhydrazone), and in experiments in which the rate of conversion of inactive complex into active complex by the phosphatase was measured in extracts of mitochondria. The inhibition of the phosphatase reaction was seen with constant concentrations of Ca2+ and Mg2+ (activators of the phosphatase). The phosphatase reaction in these mitochondrial extracts was not inhibited when an excess of exogenous pig heart pyruvate dehydrogenase phosphate was used as substrate. It is concluded that this inhibition is due to some factor(s) associated with the substrate (pyruvate dehydrogenase phosphate complex) and not to inhibition of the phosphatase as such. 3. This conclusion was verified by isolating pyruvate dehydrogenase phosphate complex, free of phosphatase, from hearts of control and diabetic rats an from heart mitochondria incubed for 1min (control) or 6min with respiratory substrates. The rates of re-activation of the inactive complexes were then measured with preparations of ox heart or rat heart phosphatase. The rates were lower (relative to controls) with inactive complex from hearts of diabetic rats or from heart mitochondria incubated for 6min with respiratory substrates. 4. The incorporation of 32Pi into inactive complex took 6min to complete in rat heart mitocondria. The extent of incorporation was consistent with three or four sites of phosphorylation in rat heart pyruvate dehydrogenase complex. 5. It is suggested that phosphorylation of sites additional to an inactivating site may inhibit the conversion of inactive complex into active complex by the phosphatase in heart mitochondria from alloxan-diabetic or 48h-starved rats or in mitochondria incubated for 6min with respiratory substrates."}
{"id": "PMID:212017", "title": "The oxidation of Pseudomonas cytochrome c-551 oxidase by potassium ferricyanide.", "content": "Stopped-flow kinetics were made of the reaction between ascorbate-reduced Pseudomonas cytochrome oxidase and potassium ferricyanide under both N2 and CO atmospheres. Under N2 three kinetic processes were observed, two being dependent on ferricyanide concentration, with second-order rate constants of 9.6 X 10(4)M-1.s-1 and 1.5 X 10(4)M-1.s-1, whereas the other was concentration-independent, with a first-order rate constant of 0.17 +/- 0.03s-1. Measurements of their kinetic difference spectra have allowed the fastest and second-fastest phases of the reaction to be assigned to direct bimolecular reactions of ferricyanide with the haem c and haem d, moieties of the enzyme respectively. Under CO, the second-order rate constant for the reaction of the haem c was, at 1.3 X 10(5)M-1.s-1, slightly enhanced over the rate in a N2 atmosphere, but the reaction velocity of the haem d1 component was greatly decreased, being apparently limited to that of the rates of CO dissociation from the molecule (0.15s-1 and 0.03s-1). The results are compared with those obtained during a previous study of the reaction of reduced Pseudomonas cytochrome oxidase with oxidized azurin.", "contents": "The oxidation of Pseudomonas cytochrome c-551 oxidase by potassium ferricyanide. Stopped-flow kinetics were made of the reaction between ascorbate-reduced Pseudomonas cytochrome oxidase and potassium ferricyanide under both N2 and CO atmospheres. Under N2 three kinetic processes were observed, two being dependent on ferricyanide concentration, with second-order rate constants of 9.6 X 10(4)M-1.s-1 and 1.5 X 10(4)M-1.s-1, whereas the other was concentration-independent, with a first-order rate constant of 0.17 +/- 0.03s-1. Measurements of their kinetic difference spectra have allowed the fastest and second-fastest phases of the reaction to be assigned to direct bimolecular reactions of ferricyanide with the haem c and haem d, moieties of the enzyme respectively. Under CO, the second-order rate constant for the reaction of the haem c was, at 1.3 X 10(5)M-1.s-1, slightly enhanced over the rate in a N2 atmosphere, but the reaction velocity of the haem d1 component was greatly decreased, being apparently limited to that of the rates of CO dissociation from the molecule (0.15s-1 and 0.03s-1). The results are compared with those obtained during a previous study of the reaction of reduced Pseudomonas cytochrome oxidase with oxidized azurin."}
{"id": "PMID:212018", "title": "Alterations in response of rat white adipocytes to insulin, noradrenaline, corticotropin and glucagon after adrenalectomy. Correction of these changes by adenosine deaminase.", "content": "1. Adipocytes isolated from rats 6--9 days after adrenalectomy had significantly increased sensitivity to insulin action against noradrenaline-stimulated lipolysis. In the presence of adenosine deaminase there was no significant difference in insulin sensitivity between cells from adrenalectomized and sham-operated rats. 2. Adipocytes from adrenalectomized rats had decreased lipolytic responses to all concentrations of noradrenaline and glucagon tested and a decreased lipolytic response to low but not high concentrations of corticotropin. There was no difference in lipolytic response to theophylline after adrenalectomy. Adenosine deaminase corrected the differences in response to noradrenaline and glucagon resulting from adrenalectomy. 3. In the presence of adenosine deaminase rates of lipolysis, after stimulation by high concentrations of noradrenaline, glucagon, corticotropin or theophylline, were the same in cells from adrenalectomized or sham-operated rats. 4. These findings and previously reported effects of adenosine and adrenalectomy on adipocyte function are discussed. It is proposed that changes in adipocyte hormone responsiveness after adrenalectomy may result from changes in adenosine metabolism or release.", "contents": "Alterations in response of rat white adipocytes to insulin, noradrenaline, corticotropin and glucagon after adrenalectomy. Correction of these changes by adenosine deaminase. 1. Adipocytes isolated from rats 6--9 days after adrenalectomy had significantly increased sensitivity to insulin action against noradrenaline-stimulated lipolysis. In the presence of adenosine deaminase there was no significant difference in insulin sensitivity between cells from adrenalectomized and sham-operated rats. 2. Adipocytes from adrenalectomized rats had decreased lipolytic responses to all concentrations of noradrenaline and glucagon tested and a decreased lipolytic response to low but not high concentrations of corticotropin. There was no difference in lipolytic response to theophylline after adrenalectomy. Adenosine deaminase corrected the differences in response to noradrenaline and glucagon resulting from adrenalectomy. 3. In the presence of adenosine deaminase rates of lipolysis, after stimulation by high concentrations of noradrenaline, glucagon, corticotropin or theophylline, were the same in cells from adrenalectomized or sham-operated rats. 4. These findings and previously reported effects of adenosine and adrenalectomy on adipocyte function are discussed. It is proposed that changes in adipocyte hormone responsiveness after adrenalectomy may result from changes in adenosine metabolism or release."}
{"id": "PMID:212020", "title": "Properties of mitochondria isolated from cyanide-sensitive and cyanide-stimulated cultures of Acanthamoeba castellanii.", "content": "1. Mitochondria isolated from cultures of Acanthamoeba castellanii exhibit respiratory control and oxidize alpha-oxoglutarate, succinate and NADH with ADP:O ratios of about 2.4, 1.4 and 1.25 respectively. 2. Mitochondria from cultures of which the respiration was stimulated up to 50% by 1mm-cyanide (type-A mitochondria) and from cyanide-sensitive cultures (type-B mitochondria) had similar respiratory-control ratios and ADP:O ratios. 3. State-3 rates of respiration were generally more cyanide-sensitive than State-4 rates, and the respiration of type-A mitochondria was more cyanide-resistant than that of type-B mitochondria. 4. Salicylhydroxamic acid alone had little effect on respiratory activities of either type of mitochondria, but when added together with cyanide, irrespective of the order of addition, inhibition was almost complete. 5. Oxidation of externally added NADH by type-A mitochondria was mainly via an oxidase with a low affinity for oxygen (K(m)[unk]15mum), which was largely cyanide-sensitive and partially antimycin A-sensitive; this electron-transport pathway was inhibited by ADP. 6. Cyanide-insensitive but salicylhydroxamic acid-sensitive respiration was stimulated by AMP and ADP, and by ATP after incubation in the presence of MgCl(2). 7. Addition of rotenone to mitochondria oxidizing alpha-oxoglutarate lowered the ADP:O ratios by about one-third and rendered inhibition by cyanide more complete. 8. The results suggest that mitochondria of A. castellanii possess branched pathways of electron transport which terminate in three separate oxidases; the proportions of electron fluxes via these pathways vary at different stages of growth.", "contents": "Properties of mitochondria isolated from cyanide-sensitive and cyanide-stimulated cultures of Acanthamoeba castellanii. 1. Mitochondria isolated from cultures of Acanthamoeba castellanii exhibit respiratory control and oxidize alpha-oxoglutarate, succinate and NADH with ADP:O ratios of about 2.4, 1.4 and 1.25 respectively. 2. Mitochondria from cultures of which the respiration was stimulated up to 50% by 1mm-cyanide (type-A mitochondria) and from cyanide-sensitive cultures (type-B mitochondria) had similar respiratory-control ratios and ADP:O ratios. 3. State-3 rates of respiration were generally more cyanide-sensitive than State-4 rates, and the respiration of type-A mitochondria was more cyanide-resistant than that of type-B mitochondria. 4. Salicylhydroxamic acid alone had little effect on respiratory activities of either type of mitochondria, but when added together with cyanide, irrespective of the order of addition, inhibition was almost complete. 5. Oxidation of externally added NADH by type-A mitochondria was mainly via an oxidase with a low affinity for oxygen (K(m)[unk]15mum), which was largely cyanide-sensitive and partially antimycin A-sensitive; this electron-transport pathway was inhibited by ADP. 6. Cyanide-insensitive but salicylhydroxamic acid-sensitive respiration was stimulated by AMP and ADP, and by ATP after incubation in the presence of MgCl(2). 7. Addition of rotenone to mitochondria oxidizing alpha-oxoglutarate lowered the ADP:O ratios by about one-third and rendered inhibition by cyanide more complete. 8. The results suggest that mitochondria of A. castellanii possess branched pathways of electron transport which terminate in three separate oxidases; the proportions of electron fluxes via these pathways vary at different stages of growth."}
{"id": "PMID:212019", "title": "A study of regulation of gluconeogenesis and the supply of cytosolic reducing equivalents for lactate formation in rat kidney-cortical-tubule fragments incubated with pyruvate.", "content": "1. Tubule fragments were isolated after treatment of rat kidney cortex with collagenase. The formation of glucose and lactate on incubation with 5mM-pyruvate was then measured under various conditions. 2. When tubule fragments were isolated from fed rats in the absence of Ca2+ and then incubated with various Ca2+ concentrations, an incubation period of 15--30 min was necessary to establish a metabolic steady state. Under these conditions glucose formation was increased by Ca2+, adrenaline or 3':5'-cyclic AMP to a greater extent than was lactate formation. Data show that appreciable lactate formation could not have resulted from glycolytic metabolism of glucose formed by gluconeogenesis during incubation. 3. When tubule fragments were isolated from fed rats in the presence of 1.27 mM-Ca2+ and adjustments made to the Ca2+ concentration at the commencement of incubation, metabolic steady state was rapidly established. Under these conditions lactate formation was almost insensitive to Ca2+ concentration (0.16--4.5 mM), whereas glucose formation varied with Ca2+ concentration in a sigmoidal manner. 3':5'-Cyclic AMP decreased this sigmoidicity. 4. Ca2+ depletion of the tissue before incubation appeared to change permanently the relationship between extracellular Ca2+ concentration and the measured rates of metabolic processes. 5. Under conditions of metabolic steady state, glucose formation by tubule fragments from fed rats was less sensitive than lactate formation to inhibition by 3-mercaptopicolinate or 2-n-butylmalonate. Lactate formation by tubule fragments prepared from 48 h-starved rats was more sensitive to these inhibitors. 6. Estimates were made of the rate of futile cycling of C3 species through pyruvate kinase. This was greater in the starved than in the fed state, was decreased by 3':5'-cyclic AMP in both the fed and the starved state, but was unaffected by Ca2+. 7. These results suggested that formation of lactate and glucose is less tightly linked in kidney cortex than in liver. A considerable amount of the supply of reducing equivalents for lactate formation did not appear to be associated with an energy-dependent translocation from mitochondria to cytosol involving a pyruvate leads to oxaloacetate leads to phosphoenolpyruvate leads to pyruvate cycle.", "contents": "A study of regulation of gluconeogenesis and the supply of cytosolic reducing equivalents for lactate formation in rat kidney-cortical-tubule fragments incubated with pyruvate. 1. Tubule fragments were isolated after treatment of rat kidney cortex with collagenase. The formation of glucose and lactate on incubation with 5mM-pyruvate was then measured under various conditions. 2. When tubule fragments were isolated from fed rats in the absence of Ca2+ and then incubated with various Ca2+ concentrations, an incubation period of 15--30 min was necessary to establish a metabolic steady state. Under these conditions glucose formation was increased by Ca2+, adrenaline or 3':5'-cyclic AMP to a greater extent than was lactate formation. Data show that appreciable lactate formation could not have resulted from glycolytic metabolism of glucose formed by gluconeogenesis during incubation. 3. When tubule fragments were isolated from fed rats in the presence of 1.27 mM-Ca2+ and adjustments made to the Ca2+ concentration at the commencement of incubation, metabolic steady state was rapidly established. Under these conditions lactate formation was almost insensitive to Ca2+ concentration (0.16--4.5 mM), whereas glucose formation varied with Ca2+ concentration in a sigmoidal manner. 3':5'-Cyclic AMP decreased this sigmoidicity. 4. Ca2+ depletion of the tissue before incubation appeared to change permanently the relationship between extracellular Ca2+ concentration and the measured rates of metabolic processes. 5. Under conditions of metabolic steady state, glucose formation by tubule fragments from fed rats was less sensitive than lactate formation to inhibition by 3-mercaptopicolinate or 2-n-butylmalonate. Lactate formation by tubule fragments prepared from 48 h-starved rats was more sensitive to these inhibitors. 6. Estimates were made of the rate of futile cycling of C3 species through pyruvate kinase. This was greater in the starved than in the fed state, was decreased by 3':5'-cyclic AMP in both the fed and the starved state, but was unaffected by Ca2+. 7. These results suggested that formation of lactate and glucose is less tightly linked in kidney cortex than in liver. A considerable amount of the supply of reducing equivalents for lactate formation did not appear to be associated with an energy-dependent translocation from mitochondria to cytosol involving a pyruvate leads to oxaloacetate leads to phosphoenolpyruvate leads to pyruvate cycle."}
{"id": "PMID:212021", "title": "The protonmotive force in bovine heart submitochondrial particles. Magnitude, sites of generation and comparison with the phosphorylation potential.", "content": "1. The magnitude of the protonmotive force in respiring bovine heart submitochondrial particles was estimated. The membrane-potential component was determined from the uptake of S14CN-ions, and the pH-gradient component from the uptake of [14C]methylamine. In each case a flow-dialysis technique was used to monitor uptake. 2. With NADH as substrate the membrane potential was approx. 145mV and the pH gradient was between 0 and 0.5 unit when the particles were suspended in a Pi/Tris reaction medium. The addition of the permeant NO3-ion decreased the membrane potential with a corresponding increase in the pH gradient. In a medium containing 200mM-sucrose, 50mM-KCl and Hepes as buffer, the total protonmotive force was 185mV, comprising a membrane potential of 90mV and a pH gradient of 1.6 units. Thus the protonmotive force was slightly larger in the high-osmolarity medium. 3. The phosphorylation potential (= deltaG0' + RT ln[ATP]/[ADP][Pi]) was approx. 43.1 kJ/mol (10.3kcal/mol) in all the reaction media tested. Comparison of this value with the protonmotive force indicates that more than 2 and up to 3 protons must be moved across the membrane for each molecule of ATP synthesized by a chemiosmotic mechanism. 4. Succinate generated both a protonmotive force and a phosphorylation potential that were of similar magnitude to those observed with NADH as substrate. 5. Although oxidation of NADH supports a rate of ATP synthesis that is approximately twice that observed with succinate, respiration with either of these substrates generated a very similar protonmotive force. Thus there seemed to be no strict relation between the size of the protonmotive force and the phosphorylation rate. 6. In the presence of antimycin and/or 2-n-heptyl-4-hydroxyquinoline N-oxide, ascorbate oxidation with either NNN'N'-tetramethyl-p-phenylenediamine or 2,3,5,6-tetramethyl-p-phenylenediamine as electron mediator generated a membrane potential of approx. 90mV, but no pH gradient was detected, even in the presence of NO3-. These data are discussed with reference to the proposal that cytochrome oxidase contains a proton pump.", "contents": "The protonmotive force in bovine heart submitochondrial particles. Magnitude, sites of generation and comparison with the phosphorylation potential. 1. The magnitude of the protonmotive force in respiring bovine heart submitochondrial particles was estimated. The membrane-potential component was determined from the uptake of S14CN-ions, and the pH-gradient component from the uptake of [14C]methylamine. In each case a flow-dialysis technique was used to monitor uptake. 2. With NADH as substrate the membrane potential was approx. 145mV and the pH gradient was between 0 and 0.5 unit when the particles were suspended in a Pi/Tris reaction medium. The addition of the permeant NO3-ion decreased the membrane potential with a corresponding increase in the pH gradient. In a medium containing 200mM-sucrose, 50mM-KCl and Hepes as buffer, the total protonmotive force was 185mV, comprising a membrane potential of 90mV and a pH gradient of 1.6 units. Thus the protonmotive force was slightly larger in the high-osmolarity medium. 3. The phosphorylation potential (= deltaG0' + RT ln[ATP]/[ADP][Pi]) was approx. 43.1 kJ/mol (10.3kcal/mol) in all the reaction media tested. Comparison of this value with the protonmotive force indicates that more than 2 and up to 3 protons must be moved across the membrane for each molecule of ATP synthesized by a chemiosmotic mechanism. 4. Succinate generated both a protonmotive force and a phosphorylation potential that were of similar magnitude to those observed with NADH as substrate. 5. Although oxidation of NADH supports a rate of ATP synthesis that is approximately twice that observed with succinate, respiration with either of these substrates generated a very similar protonmotive force. Thus there seemed to be no strict relation between the size of the protonmotive force and the phosphorylation rate. 6. In the presence of antimycin and/or 2-n-heptyl-4-hydroxyquinoline N-oxide, ascorbate oxidation with either NNN'N'-tetramethyl-p-phenylenediamine or 2,3,5,6-tetramethyl-p-phenylenediamine as electron mediator generated a membrane potential of approx. 90mV, but no pH gradient was detected, even in the presence of NO3-. These data are discussed with reference to the proposal that cytochrome oxidase contains a proton pump."}
{"id": "PMID:212022", "title": "The protonmotive force in phosphorylating membrane vesicles from Paracoccus denitrificans. Magnitude, sites of generation and comparison with the phosphorylation potential.", "content": "1. The magnitude of the protonmotive force in phosphorylating membrane vesicles from Paracoccus denitrificans was estimated. The membrane potential component was determined from the uptake of S(14)CN(-), and the transmembrane pH gradient component from the uptake of [(14)C]methylamine. In each case a flow-dialysis technique was used to monitor uptake. 2. With NADH as substrate, the membrane potential was about 145mV and the pH gradient was below 0.5 pH unit. The membrane potential was decreased by approx. 15mV during ATP synthesis, and was abolished on addition of carbonyl cyanide p-trifluoromethoxyphenylhydrazone. In the presence of KCl plus valinomycin the membrane potential was replaced by a pH gradient of 1.5 units. 3. Succinate oxidation generated a membrane potential of approx. 125mV and the pH gradient was below 0.5 pH unit. Oxidation of ascorbate (in the presence of antimycin) with either 2,3,5,6-tetramethyl-p-phenylenediamine or NNN'N'-tetramethyl-p-phenylenediamine as electron mediator usually generated a membrane potential of approx. 90mV. On occasion, ascorbate oxidation did not generate a membrane potential, suggesting that the presence of a third energy-coupling site in P. denitrificans vesicles is variable. 4. With NADH or succinate as substrate, the phosphorylation potential (DeltaG(p)=DeltaG(0)'+RTln[ATP]/ [ADP][P(i)]) was approx. 53.6kJ/mol (12.8kcal/mol). Comparison of this value with the protonmotive force indicates that more than 3 protons need to be translocated via the adenosine triphosphatase of P. denitrificans for each molecule of ATP synthesized by a chemiosmotic mechanism. In the presence of 10mm-KNO(3) the protonmotive force was not detectable (<60mV) but DeltaG(p) was not altered. This result may indicate either that there is no relationship between the protonmotive force and DeltaG(p), or that for an unidentified reason the equilibration of SCN(-) or methylamine with the membrane potential and the pH gradient is prevented by NO(3) (-) in this system.", "contents": "The protonmotive force in phosphorylating membrane vesicles from Paracoccus denitrificans. Magnitude, sites of generation and comparison with the phosphorylation potential. 1. The magnitude of the protonmotive force in phosphorylating membrane vesicles from Paracoccus denitrificans was estimated. The membrane potential component was determined from the uptake of S(14)CN(-), and the transmembrane pH gradient component from the uptake of [(14)C]methylamine. In each case a flow-dialysis technique was used to monitor uptake. 2. With NADH as substrate, the membrane potential was about 145mV and the pH gradient was below 0.5 pH unit. The membrane potential was decreased by approx. 15mV during ATP synthesis, and was abolished on addition of carbonyl cyanide p-trifluoromethoxyphenylhydrazone. In the presence of KCl plus valinomycin the membrane potential was replaced by a pH gradient of 1.5 units. 3. Succinate oxidation generated a membrane potential of approx. 125mV and the pH gradient was below 0.5 pH unit. Oxidation of ascorbate (in the presence of antimycin) with either 2,3,5,6-tetramethyl-p-phenylenediamine or NNN'N'-tetramethyl-p-phenylenediamine as electron mediator usually generated a membrane potential of approx. 90mV. On occasion, ascorbate oxidation did not generate a membrane potential, suggesting that the presence of a third energy-coupling site in P. denitrificans vesicles is variable. 4. With NADH or succinate as substrate, the phosphorylation potential (DeltaG(p)=DeltaG(0)'+RTln[ATP]/ [ADP][P(i)]) was approx. 53.6kJ/mol (12.8kcal/mol). Comparison of this value with the protonmotive force indicates that more than 3 protons need to be translocated via the adenosine triphosphatase of P. denitrificans for each molecule of ATP synthesized by a chemiosmotic mechanism. In the presence of 10mm-KNO(3) the protonmotive force was not detectable (<60mV) but DeltaG(p) was not altered. This result may indicate either that there is no relationship between the protonmotive force and DeltaG(p), or that for an unidentified reason the equilibration of SCN(-) or methylamine with the membrane potential and the pH gradient is prevented by NO(3) (-) in this system."}
{"id": "PMID:212023", "title": "Properties of a cytochrome c-enriched light particulate fraction isolated from the photosynthetic bacterium Rhodopseudomonas spheroides.", "content": "Differential centrifugation of suspensions of French-press-disrupted Rhodopseudomonas spheroides yielded a light particulate fraction that was different in many properties from the bulk membrane fraction. It was enriched in cytochrome c and had a low cytochrome b content. When prepared from photosynthetically grown cells this fraction had a very low specific bacteriochlorophyll content. The cytochrome c of the light particles differed in absorption maxima at 77K from cytochrome c2 attached to membranes; there was pronounced splitting of the alpha-band, as is found in cytochrome c2 free in solution. Potentiometric titration at A552--A540 showed the presence of two components that fitted an n = 1 titration; one component had a midpoint redox potential of +345mV, like cytochrome c2 in solution, and the second had E0' at pH 7.0 of +110 mV, and they were present in a ratio of approx. 2:3. Difference spectroscopy at 77K showed that the spectra of the two components were very similar. More of a CO-binding component was present in particles from photosynthetically grown cells. Light membranes purified by centrifugation on gradients of 5--60% (w/w) sucrose retained the two c cytochromes; they contained no detectable succinate-cytochrome c reductase or bacteriochlorophyll and very little ubiquinone, but they contained NADH-cytochrome c reductase and some phosphate. Electrophoresis on sodium dodecyl sulphate/polyacrylamide gels showed that the light membranes of aerobically and photosynthetically grown cells were very similar and differed greatly from other membrane fractions of R. spheroides.", "contents": "Properties of a cytochrome c-enriched light particulate fraction isolated from the photosynthetic bacterium Rhodopseudomonas spheroides. Differential centrifugation of suspensions of French-press-disrupted Rhodopseudomonas spheroides yielded a light particulate fraction that was different in many properties from the bulk membrane fraction. It was enriched in cytochrome c and had a low cytochrome b content. When prepared from photosynthetically grown cells this fraction had a very low specific bacteriochlorophyll content. The cytochrome c of the light particles differed in absorption maxima at 77K from cytochrome c2 attached to membranes; there was pronounced splitting of the alpha-band, as is found in cytochrome c2 free in solution. Potentiometric titration at A552--A540 showed the presence of two components that fitted an n = 1 titration; one component had a midpoint redox potential of +345mV, like cytochrome c2 in solution, and the second had E0' at pH 7.0 of +110 mV, and they were present in a ratio of approx. 2:3. Difference spectroscopy at 77K showed that the spectra of the two components were very similar. More of a CO-binding component was present in particles from photosynthetically grown cells. Light membranes purified by centrifugation on gradients of 5--60% (w/w) sucrose retained the two c cytochromes; they contained no detectable succinate-cytochrome c reductase or bacteriochlorophyll and very little ubiquinone, but they contained NADH-cytochrome c reductase and some phosphate. Electrophoresis on sodium dodecyl sulphate/polyacrylamide gels showed that the light membranes of aerobically and photosynthetically grown cells were very similar and differed greatly from other membrane fractions of R. spheroides."}
{"id": "PMID:212024", "title": "Evidence for the involvement of superoxide in vitamin K-dependent carboxylation of glutamic acid residues of prothrombin.", "content": "The formation of vitamin K epoxide and the vitamin K-dependent carboxylation of glutamic acid residues present in synthetic substrates and decarboxyprothrombin are both inhibited by superoxide dismutase. Catalase only inhibits the generation of vitamin K epoxide, suggesting that the carboxylation and epoxidation reactions are not inter-dependent.", "contents": "Evidence for the involvement of superoxide in vitamin K-dependent carboxylation of glutamic acid residues of prothrombin. The formation of vitamin K epoxide and the vitamin K-dependent carboxylation of glutamic acid residues present in synthetic substrates and decarboxyprothrombin are both inhibited by superoxide dismutase. Catalase only inhibits the generation of vitamin K epoxide, suggesting that the carboxylation and epoxidation reactions are not inter-dependent."}
{"id": "PMID:212086", "title": "Collagen production by cultures containing multinucleated cells derived from synovial fibroblasts.", "content": "Multinucleate cells are found frequently in rheumatoid synovium. In this study, polyethylene glycol was used to fuse rabbit synovial fibroblasts. Approximately 40% of the cells developed more than one nucleus in a 24 hour period, during which time cell membranes had increased permeability. In cultures containing multinucleate cells, 3H-thymidine incorporation was depressed for 24 hours although 3H-leucine incorporation into TCA precipitable material was unaffected; autoradiography showed that depression of 3H-thymidine continued for at least 4 days. Collagenase production by cultures containing fused cells was increased more than 10-fold over control cultures during a 28 day period.", "contents": "Collagen production by cultures containing multinucleated cells derived from synovial fibroblasts. Multinucleate cells are found frequently in rheumatoid synovium. In this study, polyethylene glycol was used to fuse rabbit synovial fibroblasts. Approximately 40% of the cells developed more than one nucleus in a 24 hour period, during which time cell membranes had increased permeability. In cultures containing multinucleate cells, 3H-thymidine incorporation was depressed for 24 hours although 3H-leucine incorporation into TCA precipitable material was unaffected; autoradiography showed that depression of 3H-thymidine continued for at least 4 days. Collagenase production by cultures containing fused cells was increased more than 10-fold over control cultures during a 28 day period."}
{"id": "PMID:212087", "title": "Correlation between articular cartilage collagenase activity and osteoarthritis.", "content": "Articular cartilage collagenase activity was determined for 28 sections obtained from twelve femoral heads. For each one square centimeter area, a section was graded by a histologic-histochemical grading system for the severity of the arthritis. Collagenase activity was found primarily in those areas of moderately severe disease, but not in mild or end stage arthritis.", "contents": "Correlation between articular cartilage collagenase activity and osteoarthritis. Articular cartilage collagenase activity was determined for 28 sections obtained from twelve femoral heads. For each one square centimeter area, a section was graded by a histologic-histochemical grading system for the severity of the arthritis. Collagenase activity was found primarily in those areas of moderately severe disease, but not in mild or end stage arthritis."}
{"id": "PMID:212091", "title": "Studies with primaquine in vitro: superoxide radical formation and oxidation of haemoglobin.", "content": "1. The production of superoxide radicals from primaquine diphosphate in aqueous solution has been demonstrated, using as indicator the reduction of cytochrome C with inhibition of the reaction by superoxide dismutase. 2. Primaquine-mediated oxidation of haemoglobin to methaemoglobin was reduced by the addition of catalase and increased by superoxide dismutase. Mannitol, a hydroxyl radical scavenger, abolished the increase in methaemoglobin observed in the presence of superoxide dismutase. EDTA reduced the oxidation of haemoglobin with and without superoxide dismutase. 3. Although the oxidation of haemoglobin in the presence of primaquine includes the effects of hydrogen peroxide, superoxide and hydroxyl radicals and metal ions, the results indicate that hydrogen peroxide, rather than the superoxide radical, is the main oxidizing species. The increase in haemoglobin oxidation occurring with superoxide dismutase may result from the augmented rate of hydrogen peroxide formation from superoxide radicals.", "contents": "Studies with primaquine in vitro: superoxide radical formation and oxidation of haemoglobin. 1. The production of superoxide radicals from primaquine diphosphate in aqueous solution has been demonstrated, using as indicator the reduction of cytochrome C with inhibition of the reaction by superoxide dismutase. 2. Primaquine-mediated oxidation of haemoglobin to methaemoglobin was reduced by the addition of catalase and increased by superoxide dismutase. Mannitol, a hydroxyl radical scavenger, abolished the increase in methaemoglobin observed in the presence of superoxide dismutase. EDTA reduced the oxidation of haemoglobin with and without superoxide dismutase. 3. Although the oxidation of haemoglobin in the presence of primaquine includes the effects of hydrogen peroxide, superoxide and hydroxyl radicals and metal ions, the results indicate that hydrogen peroxide, rather than the superoxide radical, is the main oxidizing species. The increase in haemoglobin oxidation occurring with superoxide dismutase may result from the augmented rate of hydrogen peroxide formation from superoxide radicals."}
{"id": "PMID:212088", "title": "Autoimmunity and the immunologic network.", "content": "Recent developments in autoimmunity suggest that there are three stages in the response to self, which can be called autorecognition, autoimmunity, and autoimmune disease. The first is physiologic and fundamental to a network theory of immunologic control that is based upon recognition of idiotypes and antigens related to the major histocompatibility complex. Many foreign antigens may be recognized immunologically only if they can be imposed upon an existing network of immunologic communication. The existence of anti-receptor autoimmune diseases (such as myasthenia gravis and Grave's disease) leads to the postulate that the immune network may normally function to help regulate hormone and other nonimmune cell surface receptors. Chronic autoimmune diseases may be caused either by genetically determined abnormalities in the immune network or by an antigenic perturbation of the network that results in unresponsiveness and tolerance of an offending agent.", "contents": "Autoimmunity and the immunologic network. Recent developments in autoimmunity suggest that there are three stages in the response to self, which can be called autorecognition, autoimmunity, and autoimmune disease. The first is physiologic and fundamental to a network theory of immunologic control that is based upon recognition of idiotypes and antigens related to the major histocompatibility complex. Many foreign antigens may be recognized immunologically only if they can be imposed upon an existing network of immunologic communication. The existence of anti-receptor autoimmune diseases (such as myasthenia gravis and Grave's disease) leads to the postulate that the immune network may normally function to help regulate hormone and other nonimmune cell surface receptors. Chronic autoimmune diseases may be caused either by genetically determined abnormalities in the immune network or by an antigenic perturbation of the network that results in unresponsiveness and tolerance of an offending agent."}
{"id": "PMID:212092", "title": "Inhibition of collagen peptidase in HeLa cells and human tumours by compounds including drugs used in cancer therapy.", "content": "Collagen-peptidase activity in extracts of HeLa cells and human tumours is inactivated by Razoxane (ICRF-159), cyclophosphamide, 5-fluorouracil, thiotepa, aprotinin, EDTA and phenanthroline. As this activity, in association with other enzymes, may contribute to tissue lysis in cancers, chemical intervention may reduce invasiveness and modify the processes of infiltration and metastasis. Accordingly, some drugs used in therapy or for the prevention of metastasis may produce their observed effects by a combination of factors including enzyme inhibition.", "contents": "Inhibition of collagen peptidase in HeLa cells and human tumours by compounds including drugs used in cancer therapy. Collagen-peptidase activity in extracts of HeLa cells and human tumours is inactivated by Razoxane (ICRF-159), cyclophosphamide, 5-fluorouracil, thiotepa, aprotinin, EDTA and phenanthroline. As this activity, in association with other enzymes, may contribute to tissue lysis in cancers, chemical intervention may reduce invasiveness and modify the processes of infiltration and metastasis. Accordingly, some drugs used in therapy or for the prevention of metastasis may produce their observed effects by a combination of factors including enzyme inhibition."}
{"id": "PMID:212093", "title": "Use of exercise challenge to investigate possible tolerance to beta-adrenoceptor stimulation in asthma.", "content": "The effect of prolonged salbutamol administration on beta-adrenoceptor function in asthma has been examined. Six adult patients received salbutamol tablets (16 mg daily) for between 4 and 20 weeks and six adolescents received salbutamol aerosol (800 microgram daily) for 2--5 weeks. Before and after the treatment period the acute bronchodilator response to inhaled salbutamol and the ability of inhaled salbutamol to protect against exercise-induced asthma were examined. Lymphocyte beta-adrenoceptor function was also measured in the patients on tablet therapy. Inhaled salbutamol was less effective in protecting against exercise-induced asthma at the end of the treatment period in the patients who had received tablet therapy, but otherwise there was no significant change in beta-receptor function of either airways or lymphocytes. This apparent loss of efficacy of inhaled salbutamol in the prevention of exercise-induced asthma in some subjects, even when its acute bronchodilator effect is preserved, might reflect differences in the susceptibility of different beta-adrenoceptors to desensitization after prolonged stimulation: its clinical importance remains uncertain.", "contents": "Use of exercise challenge to investigate possible tolerance to beta-adrenoceptor stimulation in asthma. The effect of prolonged salbutamol administration on beta-adrenoceptor function in asthma has been examined. Six adult patients received salbutamol tablets (16 mg daily) for between 4 and 20 weeks and six adolescents received salbutamol aerosol (800 microgram daily) for 2--5 weeks. Before and after the treatment period the acute bronchodilator response to inhaled salbutamol and the ability of inhaled salbutamol to protect against exercise-induced asthma were examined. Lymphocyte beta-adrenoceptor function was also measured in the patients on tablet therapy. Inhaled salbutamol was less effective in protecting against exercise-induced asthma at the end of the treatment period in the patients who had received tablet therapy, but otherwise there was no significant change in beta-receptor function of either airways or lymphocytes. This apparent loss of efficacy of inhaled salbutamol in the prevention of exercise-induced asthma in some subjects, even when its acute bronchodilator effect is preserved, might reflect differences in the susceptibility of different beta-adrenoceptors to desensitization after prolonged stimulation: its clinical importance remains uncertain."}
{"id": "PMID:212095", "title": "Effects of amino acid analogues on protein synthesis and degradation in isolated cells.", "content": "1. Naturally-occurring and synthetic analogues of phenylalanine, tyrosine, histidine, arginine, proline, tryptophan and the sulphur amino acids have beeen tested in rat reticulocytes and in the Reuber H35 hepatoma for effects on protein synthesis and protein degradation and on the heat lability of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) in the hepatoma cells. The experiments were designed to test whether the analogues could be incorporated into mammalian proteins and whether the resultant proteins would be degraded at an accelerated rate. 2. Several analogues, including thiazolylanine, triazolalanine and selenocystine both stimulated protein synthesis and produced labile protein in reticulocytes. Other analogues, such as dihydroxyphenylalanine, thioproline and pipecolic acid accelerated protein breakdown but probably indirectly via an inhibition of protein synthesis. Azetidine-2-carboxylic acid had the largest effect on protein breakdown in reticulocytes. 3. Labile protein was produced in hepatoma cells incubated in the presence of azetidine-2-carboxylic acid, canavanine, indospicine, triazolalanine, 2-, 3- and 4-fluorophenylalanine. These same analogues, together with 3,4-dehydroproline, beta-2-thienylalanine, dihydroxyphenylalanine, histidinol, 5- and 6-fluorotryptophan, selenocystine and selenomethionine produced heat-labile phosphoenolpyruvate carboxykinase. Enzyme induced in the presence of selenomethionine or indospicine showed the largest increases in heat lability, and for these analogues equimolar concentrations of methionine and arginine respectively were needed to nullify the enzyme abnormality. 4. The toxicity of the same naturally-occurring analogues has been discussed in terms of their ability to be incorporated into cell proteins.", "contents": "Effects of amino acid analogues on protein synthesis and degradation in isolated cells. 1. Naturally-occurring and synthetic analogues of phenylalanine, tyrosine, histidine, arginine, proline, tryptophan and the sulphur amino acids have beeen tested in rat reticulocytes and in the Reuber H35 hepatoma for effects on protein synthesis and protein degradation and on the heat lability of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) in the hepatoma cells. The experiments were designed to test whether the analogues could be incorporated into mammalian proteins and whether the resultant proteins would be degraded at an accelerated rate. 2. Several analogues, including thiazolylanine, triazolalanine and selenocystine both stimulated protein synthesis and produced labile protein in reticulocytes. Other analogues, such as dihydroxyphenylalanine, thioproline and pipecolic acid accelerated protein breakdown but probably indirectly via an inhibition of protein synthesis. Azetidine-2-carboxylic acid had the largest effect on protein breakdown in reticulocytes. 3. Labile protein was produced in hepatoma cells incubated in the presence of azetidine-2-carboxylic acid, canavanine, indospicine, triazolalanine, 2-, 3- and 4-fluorophenylalanine. These same analogues, together with 3,4-dehydroproline, beta-2-thienylalanine, dihydroxyphenylalanine, histidinol, 5- and 6-fluorotryptophan, selenocystine and selenomethionine produced heat-labile phosphoenolpyruvate carboxykinase. Enzyme induced in the presence of selenomethionine or indospicine showed the largest increases in heat lability, and for these analogues equimolar concentrations of methionine and arginine respectively were needed to nullify the enzyme abnormality. 4. The toxicity of the same naturally-occurring analogues has been discussed in terms of their ability to be incorporated into cell proteins."}
{"id": "PMID:212096", "title": "Role of hydrophobicity in the binding of coenzymes. Appendix. Translational and rotational contribution to the free energy of dissociation.", "content": "We calculate the loss of surface area accessible to solvent associated with coenzyme binding in Clostridium flavodoxin, in dogfish lactate dehydrogenase, and in lobster glyceraldehyde-3-phosphate dehydrogenase. The coenzymes are nearly buried in the complexes and lose on the order of 600 A2, while the proteins lose a similar amount of accessible surface area. Some of the loss can be attributed to conformation changes in the protein, at least in the case of lactate dehydrogenase, where we show that the apoenzyme has a larger accessible surface area than the holoenzyme. Using known correlations with the hydrophobic contribution to the free energy, we demonstrate that hydrophobicity is the major source of stabilization free energy in FMN binding to flavodoxin and in NAD binding to the two dehydrogenases: it contributes 25 to 30 kcal/mol to the free energy of dissociation, more than required in order to compensate for the loss of six degrees of translational/rotational freedom by the coenzyme.", "contents": "Role of hydrophobicity in the binding of coenzymes. Appendix. Translational and rotational contribution to the free energy of dissociation. We calculate the loss of surface area accessible to solvent associated with coenzyme binding in Clostridium flavodoxin, in dogfish lactate dehydrogenase, and in lobster glyceraldehyde-3-phosphate dehydrogenase. The coenzymes are nearly buried in the complexes and lose on the order of 600 A2, while the proteins lose a similar amount of accessible surface area. Some of the loss can be attributed to conformation changes in the protein, at least in the case of lactate dehydrogenase, where we show that the apoenzyme has a larger accessible surface area than the holoenzyme. Using known correlations with the hydrophobic contribution to the free energy, we demonstrate that hydrophobicity is the major source of stabilization free energy in FMN binding to flavodoxin and in NAD binding to the two dehydrogenases: it contributes 25 to 30 kcal/mol to the free energy of dissociation, more than required in order to compensate for the loss of six degrees of translational/rotational freedom by the coenzyme."}
{"id": "PMID:212097", "title": "A kinetic study of cyclic adenosine 3':5'-monophosphate binding and mode of activation of protein kinase from Drosophila melanogaster embryos.", "content": "Cyclic AMP-dependent protein kinase and its regulatory subunit were isolated from Drosophila melanogaster embryos. The profiles of cyclic AMP binding by these proteins were significantly different. In order to explain such a difference and to find the mode of enzyme activation by cyclic AMP, a kinetic study of cyclic AMP binding was carried out. First, the association rate constant k1 and dissociation rate constant k-1 in the cyclic AMP-regulatory subunit interaction at 0 degrees C were estimated to be 2.3 X 10(6)M-1s-1 and 1.1 X 10(-3)s-1, respectively. Secondly, the three possible modes of enzyme activation by cyclic AMP were mathematically considered and could be described by a unique formula: r=APt + BQt (A + B=1) in which the parameters A, B, P, and Q are equivalent to rate constants in the sense that the rate constants are simply expressed by these parameters. Thirdly, the values of the parameters and subsequently the values of rate constants involved in the possible mechanisms were evaluated using a curve-fitting technique and compared with experimental observation. It was then found that the following mechanism was the only one which fitted the experimental observations. Namely, RC + L k3 equilibrium k-3 LRC k4 equilibrium k-4 RL + C where R, C, and L represent the regulatory and catalytic subunits and cyclic AMP as a ligand. Thus, our results indicate that in the presence of cyclic AMP the active enzyme (C) is released from a ternary intermediate which is the primary product of the cyclic AMP-holoenzyme interaction. The estimated values of the rate constants are: k3=3.5 X 10(6)M-1s-1;k-3=7.3 X 10(-1)s-1;and k4=3.8 X 10(-2)s. These estimates indicate that the reaction LRC leads to RL + C is relatively slow and limits the rate of the overall reaction. By comparing k-3 and k4, it is apparent that a large part of newly formed ternary intermediate reverts to the holoenzyme.", "contents": "A kinetic study of cyclic adenosine 3':5'-monophosphate binding and mode of activation of protein kinase from Drosophila melanogaster embryos. Cyclic AMP-dependent protein kinase and its regulatory subunit were isolated from Drosophila melanogaster embryos. The profiles of cyclic AMP binding by these proteins were significantly different. In order to explain such a difference and to find the mode of enzyme activation by cyclic AMP, a kinetic study of cyclic AMP binding was carried out. First, the association rate constant k1 and dissociation rate constant k-1 in the cyclic AMP-regulatory subunit interaction at 0 degrees C were estimated to be 2.3 X 10(6)M-1s-1 and 1.1 X 10(-3)s-1, respectively. Secondly, the three possible modes of enzyme activation by cyclic AMP were mathematically considered and could be described by a unique formula: r=APt + BQt (A + B=1) in which the parameters A, B, P, and Q are equivalent to rate constants in the sense that the rate constants are simply expressed by these parameters. Thirdly, the values of the parameters and subsequently the values of rate constants involved in the possible mechanisms were evaluated using a curve-fitting technique and compared with experimental observation. It was then found that the following mechanism was the only one which fitted the experimental observations. Namely, RC + L k3 equilibrium k-3 LRC k4 equilibrium k-4 RL + C where R, C, and L represent the regulatory and catalytic subunits and cyclic AMP as a ligand. Thus, our results indicate that in the presence of cyclic AMP the active enzyme (C) is released from a ternary intermediate which is the primary product of the cyclic AMP-holoenzyme interaction. The estimated values of the rate constants are: k3=3.5 X 10(6)M-1s-1;k-3=7.3 X 10(-1)s-1;and k4=3.8 X 10(-2)s. These estimates indicate that the reaction LRC leads to RL + C is relatively slow and limits the rate of the overall reaction. By comparing k-3 and k4, it is apparent that a large part of newly formed ternary intermediate reverts to the holoenzyme."}
{"id": "PMID:212098", "title": "Characterization of soluble uterine cyclic nucleotide phosphodiesterase.", "content": "Soluble cyclic nucleotide phosphodiesterase of rat uterus displays distinct structural and regulatory properties. Like phosphodiesterases from many mammalian sources the soluble uterine enzyme system exhibits nonlinear Lineweaver--Burk kinetics with cyclic adenosine 3':5'-monophosphate (cAMP) as substrate (apparent Kms congruent to 3 and 20 micron) and linear kinetics with cyclic guanosine 3':5'-monophosphate (cGMP) as substrate (apparent Km congruent to 3 micron). Unlike most other mammalian phosphodiesterases, however, numerous separation procedures reveal only a single form of uterine phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP. A single form of the enzyme is observed upon sucrose gradient centrifugation (7.9 S), agarose gel filtration, and DEAE-cellulose chromatography at either pH 8.0 OR 6.0. Heat denaturation (50 degrees C) of soluble uterine phosphodiesterase causes the loss of both cAMP and cGMP hydrolytic activities at the same rate. Isoelectric focusing reveals major (pI = 5.2) and minor forms (pI = 5.8) of phosphodiesterase which both catalyze the hydrolysis of the two cyclic nucleotide substrates. In vivo administration of estradiol produces identical decreases in the activities of cAMP and cGMP phosphodiesterase. These results raise the possibility that the uterus contains a single form of soluble phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP.", "contents": "Characterization of soluble uterine cyclic nucleotide phosphodiesterase. Soluble cyclic nucleotide phosphodiesterase of rat uterus displays distinct structural and regulatory properties. Like phosphodiesterases from many mammalian sources the soluble uterine enzyme system exhibits nonlinear Lineweaver--Burk kinetics with cyclic adenosine 3':5'-monophosphate (cAMP) as substrate (apparent Kms congruent to 3 and 20 micron) and linear kinetics with cyclic guanosine 3':5'-monophosphate (cGMP) as substrate (apparent Km congruent to 3 micron). Unlike most other mammalian phosphodiesterases, however, numerous separation procedures reveal only a single form of uterine phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP. A single form of the enzyme is observed upon sucrose gradient centrifugation (7.9 S), agarose gel filtration, and DEAE-cellulose chromatography at either pH 8.0 OR 6.0. Heat denaturation (50 degrees C) of soluble uterine phosphodiesterase causes the loss of both cAMP and cGMP hydrolytic activities at the same rate. Isoelectric focusing reveals major (pI = 5.2) and minor forms (pI = 5.8) of phosphodiesterase which both catalyze the hydrolysis of the two cyclic nucleotide substrates. In vivo administration of estradiol produces identical decreases in the activities of cAMP and cGMP phosphodiesterase. These results raise the possibility that the uterus contains a single form of soluble phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP."}
{"id": "PMID:212103", "title": "Cross-linking of ubiquinone cytochrome c reductase (complex III) with periodate-cleavable bifunctional reagents.", "content": "Two novel cross-linkers, disuccinimidyl tartarate (DST) and N,N'-bis(3-succinimidyloxycarbonylpropyl)tartaramide (SPT), have been synthesized. These reagents span 6 and 18 A, respectively, between functional groups and contain a vic-glycol bond which can be cleaved with periodate under mild reaction conditions. Both DST and SPT have been used to examine the near-neighbor relationships of polypeptides in ubiquinone cytochrome c reductase (complex III) from beef heart mitochondria. Among the cross-linked products resolved were pairs containing I + II, II + VI, I + V, and VI + VII. Polypeptides III and IV, a cytochrome b aproprotein, and the cytochrome c1 hemoprotein, respectively, were also resolved in several cross-linked products.", "contents": "Cross-linking of ubiquinone cytochrome c reductase (complex III) with periodate-cleavable bifunctional reagents. Two novel cross-linkers, disuccinimidyl tartarate (DST) and N,N'-bis(3-succinimidyloxycarbonylpropyl)tartaramide (SPT), have been synthesized. These reagents span 6 and 18 A, respectively, between functional groups and contain a vic-glycol bond which can be cleaved with periodate under mild reaction conditions. Both DST and SPT have been used to examine the near-neighbor relationships of polypeptides in ubiquinone cytochrome c reductase (complex III) from beef heart mitochondria. Among the cross-linked products resolved were pairs containing I + II, II + VI, I + V, and VI + VII. Polypeptides III and IV, a cytochrome b aproprotein, and the cytochrome c1 hemoprotein, respectively, were also resolved in several cross-linked products."}
{"id": "PMID:212104", "title": "Lipid-protein associations in chromatophores from the photosynthetic bacterium Rhodopseudomonas sphaeroides.", "content": "Lipid-protein interactions were examined in chromatophores isolated from the photosynthetic bacterium Rhodopseudomonas sphaeroides using lipid spin-labels. The chromatophores contain fluid bilayer and a significant amount of lipid immobilized by membrane proteins. For a typical preparation of cells grown under 600 ft-c illumination, 59% of the spin-labeled fatty acids were bound. Essentially the entire length of the 18-carbon fatty acid chain was immobilized, judging from results obtained with the spin-label at the 7, 12, and 16 positions. The amount immobilized varies directly with the bacteriochlorophyll content of the chromatophore material, suggesting that a significant fraction of the lipid spin-labels is immoblized on the hydrophobic surfaces of the chlorophyll-binding proteins. Changing the lipid spin-label head group from a negatively charged carboxyl group to a positively charged quarternary amine greatly decreased the amount of immobilized lipid. The changes in immobilized lipid with light level and polar head group suggest that the anntenna bacteriochlorophyll-binding proteins preferentially associate with negatively charged lipids.", "contents": "Lipid-protein associations in chromatophores from the photosynthetic bacterium Rhodopseudomonas sphaeroides. Lipid-protein interactions were examined in chromatophores isolated from the photosynthetic bacterium Rhodopseudomonas sphaeroides using lipid spin-labels. The chromatophores contain fluid bilayer and a significant amount of lipid immobilized by membrane proteins. For a typical preparation of cells grown under 600 ft-c illumination, 59% of the spin-labeled fatty acids were bound. Essentially the entire length of the 18-carbon fatty acid chain was immobilized, judging from results obtained with the spin-label at the 7, 12, and 16 positions. The amount immobilized varies directly with the bacteriochlorophyll content of the chromatophore material, suggesting that a significant fraction of the lipid spin-labels is immoblized on the hydrophobic surfaces of the chlorophyll-binding proteins. Changing the lipid spin-label head group from a negatively charged carboxyl group to a positively charged quarternary amine greatly decreased the amount of immobilized lipid. The changes in immobilized lipid with light level and polar head group suggest that the anntenna bacteriochlorophyll-binding proteins preferentially associate with negatively charged lipids."}
{"id": "PMID:212105", "title": "Mode of coupling between the beta-adrenergic receptor and adenylate cyclase in turkey erythrocytes.", "content": "The mode of coupling of the beta-adrenergic receptor to the enzyme adenylate cyclase in turkey erythrocyte membranes was analyzed in detail. A number of experimental techniques have been used: (1) measurement of the kinetics of cyclase activation to its permanetly active state in the presence of guanylyl imidodiphosphate, as a function of hormone concentrations; (2) measurement of antagonist and agoinst binding to the beta-adrenergic receptor prior and subsequent to the enzyme activation by hormone and guanylyl imidodiphosphate. On the bases of these two approaches, all the models of receptor to enzyme coupling which involve an equilibrium between the enzyme and the receptor can be rejected. The binding and the kinetic data, however, can be fitted by two diametrically opposed models of receptor to enzyme coupling: (a) the precouped enzyme-receptor model where activation of the enzyme occurs, according to the following scheme: formula (see text) where H is the hormone, RE is the precoupled respetor-enzyme complex, k1 and k2 are the rate constants describing hormone binding, and k is the rate constant characterizing the formation of HRE' from the intermediate HRE. According to this model, the activated complex is composed of all of the interacting species. (b) The other model is the collision coupling mechanism: formula (see test) wheere KH is the horome-receptor dissociation constant, k1 is the bimolecular rate constant governing the formation of HRE, and k3 the rate constant governing the activation of the enzyme. In this case the intermediate never accumulates and constitutes only a small fraction of the total receptor and adenylate cyclase concentrations. In order to establish which of the two mechanisms governs the mode of adenylate cyclase activation by its receptor, a diagnostic experiment was performed: Progressive inactivation of the beta receptor by a specific affinity label was found to cause a decrease in the maximal binding capacity of the receptor and a proportional decrease in the rate of activation, but no change in the maximum level of activity was attained. Progressive inactivation of the enzyme by p-hydroxymercuribenzoate was found not to change the rate of activation nor the capacity of the receptor to bind hormone. Only the maximal level of activation was found to be decreased. These results are not compatible with the precoupled model of receptor and cyclase nor with floating receptor models in which an intermediate of hormone, receptor, and cyclase is in equilibrium with its reactants. The data strongly suggest that the collision coupling is the mode of coupling between the beta receptor and cyclase coupling in turkey erythrocyte membranes.", "contents": "Mode of coupling between the beta-adrenergic receptor and adenylate cyclase in turkey erythrocytes. The mode of coupling of the beta-adrenergic receptor to the enzyme adenylate cyclase in turkey erythrocyte membranes was analyzed in detail. A number of experimental techniques have been used: (1) measurement of the kinetics of cyclase activation to its permanetly active state in the presence of guanylyl imidodiphosphate, as a function of hormone concentrations; (2) measurement of antagonist and agoinst binding to the beta-adrenergic receptor prior and subsequent to the enzyme activation by hormone and guanylyl imidodiphosphate. On the bases of these two approaches, all the models of receptor to enzyme coupling which involve an equilibrium between the enzyme and the receptor can be rejected. The binding and the kinetic data, however, can be fitted by two diametrically opposed models of receptor to enzyme coupling: (a) the precouped enzyme-receptor model where activation of the enzyme occurs, according to the following scheme: formula (see text) where H is the hormone, RE is the precoupled respetor-enzyme complex, k1 and k2 are the rate constants describing hormone binding, and k is the rate constant characterizing the formation of HRE' from the intermediate HRE. According to this model, the activated complex is composed of all of the interacting species. (b) The other model is the collision coupling mechanism: formula (see test) wheere KH is the horome-receptor dissociation constant, k1 is the bimolecular rate constant governing the formation of HRE, and k3 the rate constant governing the activation of the enzyme. In this case the intermediate never accumulates and constitutes only a small fraction of the total receptor and adenylate cyclase concentrations. In order to establish which of the two mechanisms governs the mode of adenylate cyclase activation by its receptor, a diagnostic experiment was performed: Progressive inactivation of the beta receptor by a specific affinity label was found to cause a decrease in the maximal binding capacity of the receptor and a proportional decrease in the rate of activation, but no change in the maximum level of activity was attained. Progressive inactivation of the enzyme by p-hydroxymercuribenzoate was found not to change the rate of activation nor the capacity of the receptor to bind hormone. Only the maximal level of activation was found to be decreased. These results are not compatible with the precoupled model of receptor and cyclase nor with floating receptor models in which an intermediate of hormone, receptor, and cyclase is in equilibrium with its reactants. The data strongly suggest that the collision coupling is the mode of coupling between the beta receptor and cyclase coupling in turkey erythrocyte membranes."}
{"id": "PMID:212106", "title": "Nucleic acid interaction with VERO cells. A temperature barrier in the interaction pattern.", "content": "The interaction of VERO cell monolayers with spin (nitroxide)-(labeled polynucleotides (1(N)n) was examined by electron spin resonance (ESR) spectroscopy at various temperatures. Nitroxide labels covalently linked to (A)n, (dUfl)n, (U)n and (A)n . (U)n were used to monitor the interaction. The VERO cells were grown on small quartz plates with a cell viability of 95% or better and then used directly for the ESR studies. The ESR results indicated that the interaction between VERO cells and spin-labeled nucleic acids is temperature dependent. No temperature dependence was found when VERO cells were in contact with nitroxide radicals which were free in solution or covalently bound to Sepharose 4B. The temperature dependence established with nitroxide-labeled nucleic acids indicates that a temperature barrier must exist between 20 and 26 degrees C for the interaction between nucleic acids and VERO cells; namely, at 26 degrees C or above spin-labeled nucleic acids interact significantly with a VERO cell surface; whereas, at 20 degrees C the ESR signal reports no interaction. It is concluded that a temperature-dependent phase transition of membrane components or cell surface products active at 26 degrees C or above play a key role in the nucleic acid cell surface interaction process.", "contents": "Nucleic acid interaction with VERO cells. A temperature barrier in the interaction pattern. The interaction of VERO cell monolayers with spin (nitroxide)-(labeled polynucleotides (1(N)n) was examined by electron spin resonance (ESR) spectroscopy at various temperatures. Nitroxide labels covalently linked to (A)n, (dUfl)n, (U)n and (A)n . (U)n were used to monitor the interaction. The VERO cells were grown on small quartz plates with a cell viability of 95% or better and then used directly for the ESR studies. The ESR results indicated that the interaction between VERO cells and spin-labeled nucleic acids is temperature dependent. No temperature dependence was found when VERO cells were in contact with nitroxide radicals which were free in solution or covalently bound to Sepharose 4B. The temperature dependence established with nitroxide-labeled nucleic acids indicates that a temperature barrier must exist between 20 and 26 degrees C for the interaction between nucleic acids and VERO cells; namely, at 26 degrees C or above spin-labeled nucleic acids interact significantly with a VERO cell surface; whereas, at 20 degrees C the ESR signal reports no interaction. It is concluded that a temperature-dependent phase transition of membrane components or cell surface products active at 26 degrees C or above play a key role in the nucleic acid cell surface interaction process."}
{"id": "PMID:212107", "title": "In vitro translation of nematode cuticular collagens.", "content": "Phenanthroline treatment of growing cultures of the free-living nematode Panagrellus silusiae was used to lower the degree of hydroxylation of nascent collagen chains at the polysomal level. Under these conditions, the bound pentasome-hexasome fraction provided substrate for prolyl hydroxylase. When this polysomal fraction was subsequently tested in a cell-free wheat germ system, collagenase-susceptible translation products were observed after sodium dodecyl sulfate-acrylamide gel electrophoresis. The electrophoretic mobilities of each of these four major collagen products were similar to four collagens that are isolated from intact cuticles. In addition, purified polysomal RNA that adhered to unmodified cellulose directed the synthesis of four pepsin-resistant polypeptides that had molecular weights that coincided with four pepsin-resistant collagens that can be purified from the cuticle of this species. Thus, the polysomal site of the messenger RNAs for the cuticular collagens of P. silusiae was located. Although precursor forms of the cuticular collagens were not produced in the cell-free system, the question whether additional amino acid segments occur on the primary translational products of the cuticular collagens in vivo remains open.", "contents": "In vitro translation of nematode cuticular collagens. Phenanthroline treatment of growing cultures of the free-living nematode Panagrellus silusiae was used to lower the degree of hydroxylation of nascent collagen chains at the polysomal level. Under these conditions, the bound pentasome-hexasome fraction provided substrate for prolyl hydroxylase. When this polysomal fraction was subsequently tested in a cell-free wheat germ system, collagenase-susceptible translation products were observed after sodium dodecyl sulfate-acrylamide gel electrophoresis. The electrophoretic mobilities of each of these four major collagen products were similar to four collagens that are isolated from intact cuticles. In addition, purified polysomal RNA that adhered to unmodified cellulose directed the synthesis of four pepsin-resistant polypeptides that had molecular weights that coincided with four pepsin-resistant collagens that can be purified from the cuticle of this species. Thus, the polysomal site of the messenger RNAs for the cuticular collagens of P. silusiae was located. Although precursor forms of the cuticular collagens were not produced in the cell-free system, the question whether additional amino acid segments occur on the primary translational products of the cuticular collagens in vivo remains open."}
{"id": "PMID:212108", "title": "Phosphatidate phosphatase: activity and properties in fetal and adult rat lung.", "content": "The purpose of this work is to compare the properties of phosphatidate phosphatase (L-alpha-phosphatidate phosphohydrolase, EC 3.1.3.4) in fetal and adult rat lung and to establish the developmental profile of activity measured under optimal conditions. The maximal pH of 6.0--7.0 and the inhibition by fluoride, Ca2+ and detergents were simialr for both adult and fetal. Phosphatidate phosphohydrolase activity was located in both mitochondria and microsomes. The localizations of marker enzymes indicated that the activity in these subfractions was not a result of cross contaminations. Very low activity was detected in the supernatant fraction and no Mg2+ requirement was demonstrable. The activity in the particulate fraction was about 50% of the adult from 18 day gestation until birth. Following birth, the activity rapidly increased to adult levels. Dipalmitoyl, dioleoyl and diacyl glycerol 3-phosphates are all utilized well as substrates. 1,2-dipalmitoyl-sn-glycerol 3-phosphate was hydrolyzed  faster under maximal conditions. The velocity-substrate curves tended to be sigmoidal, particularly when 1,2-dipalmitoyl-sn-glycerol 3-phosphate was the substrate. Estimated apparent Km values of 0.02--0.03 mM were obtained for fetal and adult preparations.", "contents": "Phosphatidate phosphatase: activity and properties in fetal and adult rat lung. The purpose of this work is to compare the properties of phosphatidate phosphatase (L-alpha-phosphatidate phosphohydrolase, EC 3.1.3.4) in fetal and adult rat lung and to establish the developmental profile of activity measured under optimal conditions. The maximal pH of 6.0--7.0 and the inhibition by fluoride, Ca2+ and detergents were simialr for both adult and fetal. Phosphatidate phosphohydrolase activity was located in both mitochondria and microsomes. The localizations of marker enzymes indicated that the activity in these subfractions was not a result of cross contaminations. Very low activity was detected in the supernatant fraction and no Mg2+ requirement was demonstrable. The activity in the particulate fraction was about 50% of the adult from 18 day gestation until birth. Following birth, the activity rapidly increased to adult levels. Dipalmitoyl, dioleoyl and diacyl glycerol 3-phosphates are all utilized well as substrates. 1,2-dipalmitoyl-sn-glycerol 3-phosphate was hydrolyzed  faster under maximal conditions. The velocity-substrate curves tended to be sigmoidal, particularly when 1,2-dipalmitoyl-sn-glycerol 3-phosphate was the substrate. Estimated apparent Km values of 0.02--0.03 mM were obtained for fetal and adult preparations."}
{"id": "PMID:212110", "title": "Cholesteryl ester exchange protein in human plasma isolation and characterization.", "content": "A protein catalyzing the exchange of cholesteryl esters among the lipoproteins was found in human plasma. A rapid method for assaying this activity was developed based on the transfer of radioactive cholesteryl esters from low density lipoprotein with MnCl2 in the presence of phosphate. Fractionation of plasma through a combination of ammonium sulfate precipitation, ultracentrifugation at p = 1.25, and chromatography on Phenyl-Sepharose, CM-cellulose, and concanavalin A-Sepharose, yielded a preparation purified 3500-fold compared to the starting plasma. The exchange protein was found to be a glycoprotein with an isoelectric point of 5 and apparent molecular weight of 80 000. On the basis of these properties and its immunological characteristics the exchange protein was judged to be distinct from any of the known apolipoproteins. This protein could also be separated from plasma phosphatidylcholine cholesterol acyl-transferase on DEAE-cellulose. The exchange protein did not appear to influence cholesterol esterification in lipoproteins by phosphatidylcholine cholesterol acyl-transferase, and the latter had no effect on the transfer of low density lipoprotein cholesteryl esters to high density lipoprotein. The exchange protein did not esterify cholesterol or hydrolyze cholesteryl esters in lipoproteins.", "contents": "Cholesteryl ester exchange protein in human plasma isolation and characterization. A protein catalyzing the exchange of cholesteryl esters among the lipoproteins was found in human plasma. A rapid method for assaying this activity was developed based on the transfer of radioactive cholesteryl esters from low density lipoprotein with MnCl2 in the presence of phosphate. Fractionation of plasma through a combination of ammonium sulfate precipitation, ultracentrifugation at p = 1.25, and chromatography on Phenyl-Sepharose, CM-cellulose, and concanavalin A-Sepharose, yielded a preparation purified 3500-fold compared to the starting plasma. The exchange protein was found to be a glycoprotein with an isoelectric point of 5 and apparent molecular weight of 80 000. On the basis of these properties and its immunological characteristics the exchange protein was judged to be distinct from any of the known apolipoproteins. This protein could also be separated from plasma phosphatidylcholine cholesterol acyl-transferase on DEAE-cellulose. The exchange protein did not appear to influence cholesterol esterification in lipoproteins by phosphatidylcholine cholesterol acyl-transferase, and the latter had no effect on the transfer of low density lipoprotein cholesteryl esters to high density lipoprotein. The exchange protein did not esterify cholesterol or hydrolyze cholesteryl esters in lipoproteins."}
{"id": "PMID:212111", "title": "A spectrophotometric method for determination of sphingomyelinase.", "content": "A colored derivative of sphingomyelin was synthesized and used as substrate for several sphingomyelinases. The compound is N-omega-trinitrophenyl-aminolaurylsphingosylphosphorylcholine. The rate of hydrolysis of this substrate was compared to that of bovine brain sphingomyelin, labelled with tritium in the choline moiety. The following enzyme preparations were used: homogenate-less debris of brain, assayed at pH 5.0 or 7.4; a solubilized preparation derived from rat brain lysosomes, assayed at pH 5.0 and a purified enzyme of Staphylococcus aureus. With all preparations, the rates of hydrolysis of the yellow derivative were very similar to those of the brain sphingomyelin. Extracts of skin fibroblasts of normal and Niemann-Pick patients as well as amniotic cells were also used. Again, the rates of hydrolysis of the yellow derivative practically equalled those using brain sphingomyelin.", "contents": "A spectrophotometric method for determination of sphingomyelinase. A colored derivative of sphingomyelin was synthesized and used as substrate for several sphingomyelinases. The compound is N-omega-trinitrophenyl-aminolaurylsphingosylphosphorylcholine. The rate of hydrolysis of this substrate was compared to that of bovine brain sphingomyelin, labelled with tritium in the choline moiety. The following enzyme preparations were used: homogenate-less debris of brain, assayed at pH 5.0 or 7.4; a solubilized preparation derived from rat brain lysosomes, assayed at pH 5.0 and a purified enzyme of Staphylococcus aureus. With all preparations, the rates of hydrolysis of the yellow derivative were very similar to those of the brain sphingomyelin. Extracts of skin fibroblasts of normal and Niemann-Pick patients as well as amniotic cells were also used. Again, the rates of hydrolysis of the yellow derivative practically equalled those using brain sphingomyelin."}
{"id": "PMID:212112", "title": "[ESR study of the superslow diffusion of lysozyme macroradicals in an aqueous matrix].", "content": "Using kinetic data on recombination macroradicals in freezed water solutions of lyzozyme, superslow molecular motions of biopolymer have been studied. Recombination of macroradicals is observed at 160--240 K and it has a stepwise character. The kinetic data are described quantitatively by the model, in which the set of processes with different rate constants is considered (the so-called model of polychromatic kinetics). It has been shown that polychromatic character of the process is conditioned by energy activation distribution, which is changed from Emin = 8+/-1 kcal/mol to Emax = 13 +/- 1 kcal/mol with \"rectangular\" distribution function f(E) approximately equal to: formula: (see text). Preexponential factor K0 = 2 . 10 (-9)cm3.s-1. The recombination-kinetic method used permits to estimate frequencies (inverse correlation time) translation mobility macroradicals of protein up to the frequency order 10(-2)s-1 (or velocities of motions approximately 1 A/s).", "contents": "[ESR study of the superslow diffusion of lysozyme macroradicals in an aqueous matrix]. Using kinetic data on recombination macroradicals in freezed water solutions of lyzozyme, superslow molecular motions of biopolymer have been studied. Recombination of macroradicals is observed at 160--240 K and it has a stepwise character. The kinetic data are described quantitatively by the model, in which the set of processes with different rate constants is considered (the so-called model of polychromatic kinetics). It has been shown that polychromatic character of the process is conditioned by energy activation distribution, which is changed from Emin = 8+/-1 kcal/mol to Emax = 13 +/- 1 kcal/mol with \"rectangular\" distribution function f(E) approximately equal to: formula: (see text). Preexponential factor K0 = 2 . 10 (-9)cm3.s-1. The recombination-kinetic method used permits to estimate frequencies (inverse correlation time) translation mobility macroradicals of protein up to the frequency order 10(-2)s-1 (or velocities of motions approximately 1 A/s)."}
{"id": "PMID:212113", "title": "[Study of the diffusion of water absorbed on proteins by the ESR methods using a new magnetic field impulse gradient program].", "content": "Modification of the program of impulse gradient removing anomalous suppression of the echo at small time intervals between gradient impulses is presented. The results are given of measuring the diffusion of water adsorbed on bovine serum albumin. An efficient diffusion coefficient for 20 degrees C is evaluated as 2.4.10(-6) cm2 sec at the activation energy in the temperature range 5 divided by 40 degrees C for 0.42 g H2O/g of protein and 20 divided by 50 degrees C for 0.22 g H2O/g of protein equal to 6.5 kcal/mol.", "contents": "[Study of the diffusion of water absorbed on proteins by the ESR methods using a new magnetic field impulse gradient program]. Modification of the program of impulse gradient removing anomalous suppression of the echo at small time intervals between gradient impulses is presented. The results are given of measuring the diffusion of water adsorbed on bovine serum albumin. An efficient diffusion coefficient for 20 degrees C is evaluated as 2.4.10(-6) cm2 sec at the activation energy in the temperature range 5 divided by 40 degrees C for 0.42 g H2O/g of protein and 20 divided by 50 degrees C for 0.22 g H2O/g of protein equal to 6.5 kcal/mol."}
{"id": "PMID:212115", "title": "[Study of electron transport in the photosynthetic systems of higher plants by the ESR method. VI. Kinetics of photo-induced P700 redox transitions in a system of continuous and flash illumination of different duration].", "content": "The kinetics of P700 redox-transients in leaves and isolated been and spinach chloroplasts was studied by the ESR method. P700 oxidation after a short flash (less than 10 microseconds) of white light was not resolved. P700 oxidation may be resolved only after \"long\" (more than 500 microseconds) flash of red light (700 or 720 nm) with a slow reduction of P700+ in the dark. In case of 500 microseconds flash exciting both photosystems (600 nm) P700 response was not observed. Fast P700+ reduction was observed if the short pulse of white light was given simultaneously with a continuous background 707 nm light. We can conclude from these data that P700+ accepts an electron from its primary donor within 10--500 microseconds.", "contents": "[Study of electron transport in the photosynthetic systems of higher plants by the ESR method. VI. Kinetics of photo-induced P700 redox transitions in a system of continuous and flash illumination of different duration]. The kinetics of P700 redox-transients in leaves and isolated been and spinach chloroplasts was studied by the ESR method. P700 oxidation after a short flash (less than 10 microseconds) of white light was not resolved. P700 oxidation may be resolved only after \"long\" (more than 500 microseconds) flash of red light (700 or 720 nm) with a slow reduction of P700+ in the dark. In case of 500 microseconds flash exciting both photosystems (600 nm) P700 response was not observed. Fast P700+ reduction was observed if the short pulse of white light was given simultaneously with a continuous background 707 nm light. We can conclude from these data that P700+ accepts an electron from its primary donor within 10--500 microseconds."}
{"id": "PMID:212116", "title": "[Analysis of the ESR spectra of irradiated liver and hepatoma specimens].", "content": "The analysis of ESR low temperature spectra of in vitro gamma-irradiated (1 Mrad) liver, hepatoma 22-a and tumor host liver has been carried out. On the ground of differences in thermostability and relaxation parameters of paramagnetic centres it has been shown, that there is a large amount of different paramagnetic centres in irradiated normal and tumor tissues. The ESR spectra parameters and properties of observed paramagnetic centres are presented. The main result is the detection of a specific \"tumor signal\" (asymmetrical singlet deltaH = 6, Oe, g = 2.005) and peroxide radical ROO. signal in tumor and tumor host liver.", "contents": "[Analysis of the ESR spectra of irradiated liver and hepatoma specimens]. The analysis of ESR low temperature spectra of in vitro gamma-irradiated (1 Mrad) liver, hepatoma 22-a and tumor host liver has been carried out. On the ground of differences in thermostability and relaxation parameters of paramagnetic centres it has been shown, that there is a large amount of different paramagnetic centres in irradiated normal and tumor tissues. The ESR spectra parameters and properties of observed paramagnetic centres are presented. The main result is the detection of a specific \"tumor signal\" (asymmetrical singlet deltaH = 6, Oe, g = 2.005) and peroxide radical ROO. signal in tumor and tumor host liver."}
{"id": "PMID:212121", "title": "Binding of platinum to human transferrin.", "content": "A complex of platinum and human transferrin has been formed by appropriately combining apotransferrin (metal free protein) and potassiumchloroplatinate (K2PtCl4). Atomic absorption spectroscopy indicated that both primary bind sites on the protein participated in the complex. Electron paramagnetic resonance (EPR) examination showed that the bound platinum was not paramagnetic, and thus it is highly probable that the Pt ion is in the +2 oxidation state. The results suggest a possible mechanism for physiological distribution of third-transition-series metals.", "contents": "Binding of platinum to human transferrin. A complex of platinum and human transferrin has been formed by appropriately combining apotransferrin (metal free protein) and potassiumchloroplatinate (K2PtCl4). Atomic absorption spectroscopy indicated that both primary bind sites on the protein participated in the complex. Electron paramagnetic resonance (EPR) examination showed that the bound platinum was not paramagnetic, and thus it is highly probable that the Pt ion is in the +2 oxidation state. The results suggest a possible mechanism for physiological distribution of third-transition-series metals."}
{"id": "PMID:212122", "title": "The ontogenetic evolution of acidic phosphoprotein phosphatase activity in the lymphatic tissue and the liver of the rat.", "content": "We have shown that an acidic phosphoprotein phosphatase (APP-ase) has a different pattern of postnatal maturation in the spleen, thymus and liver of rats and mice. The APP-ase activity increases during the first eight months of postnatal life in the spleen of rats (when it attains an 8--10 times higher value than at birth) and up to the sixth month of life in the spleen of mice. It increases considerably during the first two weeks of postnatal life in the thymus of rats and mice; in the liver of rats it reaches maximum activity before birth, but continues to increase up to the sixth month of postnatal life in the liver of mice. The results show also that the APP-ase from the spleen, thymus and liver of rats is equally active in dephosphorylating ATP and phenyl phosphate during the whole life span of rats, but not in relation to beta-glycerol phosphate. After analyzing its substrate specificity, its pH dependence in relation to different substrates, its kinetic properties, as well as its behaviour towards ascorbic acid and different inhibitors (sodium tungstate and sodium molybdate, L-tartrate, L-phenylalanine and L-cysteine) we have come to the conclusion that the rat spleen APP-ase is different from \"nonspecific\" acid and alkaline phosphatases and very similar to the EC 3.1.3.16 acid phosphoprotein phosphatase.", "contents": "The ontogenetic evolution of acidic phosphoprotein phosphatase activity in the lymphatic tissue and the liver of the rat. We have shown that an acidic phosphoprotein phosphatase (APP-ase) has a different pattern of postnatal maturation in the spleen, thymus and liver of rats and mice. The APP-ase activity increases during the first eight months of postnatal life in the spleen of rats (when it attains an 8--10 times higher value than at birth) and up to the sixth month of life in the spleen of mice. It increases considerably during the first two weeks of postnatal life in the thymus of rats and mice; in the liver of rats it reaches maximum activity before birth, but continues to increase up to the sixth month of postnatal life in the liver of mice. The results show also that the APP-ase from the spleen, thymus and liver of rats is equally active in dephosphorylating ATP and phenyl phosphate during the whole life span of rats, but not in relation to beta-glycerol phosphate. After analyzing its substrate specificity, its pH dependence in relation to different substrates, its kinetic properties, as well as its behaviour towards ascorbic acid and different inhibitors (sodium tungstate and sodium molybdate, L-tartrate, L-phenylalanine and L-cysteine) we have come to the conclusion that the rat spleen APP-ase is different from \"nonspecific\" acid and alkaline phosphatases and very similar to the EC 3.1.3.16 acid phosphoprotein phosphatase."}
{"id": "PMID:212118", "title": "[Participation of free radicals in ATP synthesis].", "content": "To study ESR absorption of mitochondrial ATPase a special flow system was developed allowing to maintain surviving conditions for mitochondria. It has been shown that ESR free radical signal of mitochondria observed at room temperature (g-factor 2.00 and halfwidth of about 15 Gs) depends on their metabolic state. An increase of free radical content during mitochondrial energization can be associated with operation of ATPsynthetase. It is supposed that free radicals take part in the reaction of ADP phosphorylation and that a molecule of ADP itself bound in the active centre of ATPase can become a free radical to facilitate the process of inorganic phosphate incorporation.", "contents": "[Participation of free radicals in ATP synthesis]. To study ESR absorption of mitochondrial ATPase a special flow system was developed allowing to maintain surviving conditions for mitochondria. It has been shown that ESR free radical signal of mitochondria observed at room temperature (g-factor 2.00 and halfwidth of about 15 Gs) depends on their metabolic state. An increase of free radical content during mitochondrial energization can be associated with operation of ATPsynthetase. It is supposed that free radicals take part in the reaction of ADP phosphorylation and that a molecule of ADP itself bound in the active centre of ATPase can become a free radical to facilitate the process of inorganic phosphate incorporation."}
{"id": "PMID:212119", "title": "[EPR study of redox titration of Chromatium minutissimum chromatophores].", "content": "Redox titration of chromatophores through the region +300 +570 mV at room temperature results in generation of two dark ESR signals, a well-known reaction center signal and a new narrow line. This line is characterized by deltaH pp = 4.2 Oe, g-factor about that of RC and a Lorentzian shape. It is insensitive to illumination. The determination of an RC signal midpoint potential is affected by the presence of the narrow line. Taking into account the superposition of the two ESR signals it was measured to be +(486+/-+/-18)mV.", "contents": "[EPR study of redox titration of Chromatium minutissimum chromatophores]. Redox titration of chromatophores through the region +300 +570 mV at room temperature results in generation of two dark ESR signals, a well-known reaction center signal and a new narrow line. This line is characterized by deltaH pp = 4.2 Oe, g-factor about that of RC and a Lorentzian shape. It is insensitive to illumination. The determination of an RC signal midpoint potential is affected by the presence of the narrow line. Taking into account the superposition of the two ESR signals it was measured to be +(486+/-+/-18)mV."}
{"id": "PMID:212126", "title": "[The role of copper atoms in the cytochrome oxidase reaction].", "content": "It was found that cytochrome oxidase from bovine cardiac muscle possesses marked superoxide dismutase activity. Superoxide dismutase activity is inhibited by cyanide and azide or by alkaline or thermal treatments. This activity is also suppressed by chelating agents, e.g. bathocuproin. The data obtained indicate that superoxide dismutase activity of cytochrome oxidase is due to the copper atoms of the enzyme. The experiments on the copper-containing subunit support this conclusion. Possible physiological significance of superoxide dismutase activity of cytochrome oxidase is discussed.", "contents": "[The role of copper atoms in the cytochrome oxidase reaction]. It was found that cytochrome oxidase from bovine cardiac muscle possesses marked superoxide dismutase activity. Superoxide dismutase activity is inhibited by cyanide and azide or by alkaline or thermal treatments. This activity is also suppressed by chelating agents, e.g. bathocuproin. The data obtained indicate that superoxide dismutase activity of cytochrome oxidase is due to the copper atoms of the enzyme. The experiments on the copper-containing subunit support this conclusion. Possible physiological significance of superoxide dismutase activity of cytochrome oxidase is discussed."}
{"id": "PMID:212127", "title": "[Some properties of glial membrane Na, K-ATPase].", "content": "Na,K-ATPase activity in glial membranes is rather low that in the nerve ending membranes, but is characterized by the same kind of Na+/K+-dependence. Glial Na,K-ATPase is insensitive to acetylcholine (ACh), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) while norepinephrine activates Na,K-ATPase at low concentrations and inhibits it at high concentrations. Participation of Na,K-ATPase in the regulatory mechanisms of the neuron-neuroglia relations is discussed.", "contents": "[Some properties of glial membrane Na, K-ATPase]. Na,K-ATPase activity in glial membranes is rather low that in the nerve ending membranes, but is characterized by the same kind of Na+/K+-dependence. Glial Na,K-ATPase is insensitive to acetylcholine (ACh), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) while norepinephrine activates Na,K-ATPase at low concentrations and inhibits it at high concentrations. Participation of Na,K-ATPase in the regulatory mechanisms of the neuron-neuroglia relations is discussed."}
{"id": "PMID:212128", "title": "[Polypeptide synthetase activity of chromatin from eukaryotic cells].", "content": "It is shown that the polypeptide synthetase activity (PS-activity) of chromatin from rat liver is increased 9--21 hrs after partial hepatectomy. Among 9 amino acids studied alanine, methionine, lysine, tyrosine and arginine are not incorporated into the system in question. The highest rate of polymerization is observed in case of glutamic acid. The rate of glutamine, asparagine and glycine incorporation is 7--8 times slower. The PS-activity of chromatin is enhanced by chromatin preincubation with NAD (but not with its analogs). The activation is prevented by thymidine and nicotinamide. Storage of chromatin for 18 hrs at 2--4 degrees C results in a complete loss of PS-activity. Ability of \"old\" chromatin to incorporate of amino acids may be restored by its preincubation with NAD. Storage of chromatin in the presence of 5 mM cAMP does not decrease the PS-activity. It is assumed that in the system described poly-ADP ribose is an energy source for amino acid activation.", "contents": "[Polypeptide synthetase activity of chromatin from eukaryotic cells]. It is shown that the polypeptide synthetase activity (PS-activity) of chromatin from rat liver is increased 9--21 hrs after partial hepatectomy. Among 9 amino acids studied alanine, methionine, lysine, tyrosine and arginine are not incorporated into the system in question. The highest rate of polymerization is observed in case of glutamic acid. The rate of glutamine, asparagine and glycine incorporation is 7--8 times slower. The PS-activity of chromatin is enhanced by chromatin preincubation with NAD (but not with its analogs). The activation is prevented by thymidine and nicotinamide. Storage of chromatin for 18 hrs at 2--4 degrees C results in a complete loss of PS-activity. Ability of \"old\" chromatin to incorporate of amino acids may be restored by its preincubation with NAD. Storage of chromatin in the presence of 5 mM cAMP does not decrease the PS-activity. It is assumed that in the system described poly-ADP ribose is an energy source for amino acid activation."}
{"id": "PMID:212129", "title": "[The role of histidine residues of formate dehydrogenase from Bacterium sp. 1].", "content": "The reaction between formate dehydrogenase from Bacterium sp. 1 and diethylpyrocarbonate results in the enzyme inactivation. 4 histidine residues can be blocked per subunit by this reagent. The enzyme activity correlates with the disappearance of free histidines. The process of enzyme inactivation is biphasic and obeys pseudo-first-order kinetics. NAD and NADH slow down the rate of inactivation, but do not protect histidine residues against modification. Formate does not protect the enzyme. The modification of 80% of histidines increases the Km value for both substrates 3-fold. The general conformation of enzyme in the course of modification is preserved. The modification of histidines markedly decreases the reactivity of an essential SH-group of formate dehydrogenase against the Ellman reagent.", "contents": "[The role of histidine residues of formate dehydrogenase from Bacterium sp. 1]. The reaction between formate dehydrogenase from Bacterium sp. 1 and diethylpyrocarbonate results in the enzyme inactivation. 4 histidine residues can be blocked per subunit by this reagent. The enzyme activity correlates with the disappearance of free histidines. The process of enzyme inactivation is biphasic and obeys pseudo-first-order kinetics. NAD and NADH slow down the rate of inactivation, but do not protect histidine residues against modification. Formate does not protect the enzyme. The modification of 80% of histidines increases the Km value for both substrates 3-fold. The general conformation of enzyme in the course of modification is preserved. The modification of histidines markedly decreases the reactivity of an essential SH-group of formate dehydrogenase against the Ellman reagent."}
{"id": "PMID:212130", "title": "[Factors regulating gluconeogenesis in chick embryo liver].", "content": "The ratio NAD+/NADH in cytoplasm and mitochondria of chicken embryo liver does not change up to the stage of hatching. After the hatching this ratio decreases 2-fold in both cytoplasm and mitochondria. The hatching is also accompanied by the decrease of total and mitochondrial contents of oxaloacetate and of oxaloacetate/malate ratio, the activity of citrate synthase and the ratio acetyl-CoA/CoA being unchanged.", "contents": "[Factors regulating gluconeogenesis in chick embryo liver]. The ratio NAD+/NADH in cytoplasm and mitochondria of chicken embryo liver does not change up to the stage of hatching. After the hatching this ratio decreases 2-fold in both cytoplasm and mitochondria. The hatching is also accompanied by the decrease of total and mitochondrial contents of oxaloacetate and of oxaloacetate/malate ratio, the activity of citrate synthase and the ratio acetyl-CoA/CoA being unchanged."}
{"id": "PMID:212131", "title": "Angiotensin-I-converting enzyme activity in term and premature infants.", "content": "Cord blood angiotensin-I-converting enzyme (ACE) activity was examined in 21 term and 21 premature infants. Values were significantly higher in premature infants than in term infants. Cord blood ACE activity was found to have a significant negative correlation with birth weight and gestational age. ACE activity measured from peripheral blood during the first 24 h of life was higher in premature than term infants but similar to levels in maternal and adult controls. It was not possible to predict those premature infants who would develop respiratory distress syndrome on the basis of cord blood ACE activity. However, ACE may serve as a marker for maturation of the pulmonary vascular endothelial cell.", "contents": "Angiotensin-I-converting enzyme activity in term and premature infants. Cord blood angiotensin-I-converting enzyme (ACE) activity was examined in 21 term and 21 premature infants. Values were significantly higher in premature infants than in term infants. Cord blood ACE activity was found to have a significant negative correlation with birth weight and gestational age. ACE activity measured from peripheral blood during the first 24 h of life was higher in premature than term infants but similar to levels in maternal and adult controls. It was not possible to predict those premature infants who would develop respiratory distress syndrome on the basis of cord blood ACE activity. However, ACE may serve as a marker for maturation of the pulmonary vascular endothelial cell."}
{"id": "PMID:212135", "title": "[Mechanisms of inhibition of synaptic transmission in the sympathetic ganglia of rats with alloxan diabetes].", "content": "In experiments on the isolated superior cervical sympathetic ganglia of rats with alloxan diabetes rhythmic stimulation of preganglionic nerves was effected; summation presynaptic spikes and EPSPs of ganglionic neurons were registered. In rats with moderately severe alloxan diabetes progressive depression of rhythmic ganglion potentials was connected with suppression of the mediator emission to the impulse due to rapid exhaustion of its operational fraction. Rats with severe diabetes displayed also postsynaptic suppression of the ganglionic neurons. Dynamic characteristics of the transmitter turnover assessed on the basis of consideration of the successive patterns of posttetanic potentiation showed insignificant changes in the mediator output and a significant (by 38%) suppression of the mediator reserve per sec in comparison with control.", "contents": "[Mechanisms of inhibition of synaptic transmission in the sympathetic ganglia of rats with alloxan diabetes]. In experiments on the isolated superior cervical sympathetic ganglia of rats with alloxan diabetes rhythmic stimulation of preganglionic nerves was effected; summation presynaptic spikes and EPSPs of ganglionic neurons were registered. In rats with moderately severe alloxan diabetes progressive depression of rhythmic ganglion potentials was connected with suppression of the mediator emission to the impulse due to rapid exhaustion of its operational fraction. Rats with severe diabetes displayed also postsynaptic suppression of the ganglionic neurons. Dynamic characteristics of the transmitter turnover assessed on the basis of consideration of the successive patterns of posttetanic potentiation showed insignificant changes in the mediator output and a significant (by 38%) suppression of the mediator reserve per sec in comparison with control."}
{"id": "PMID:212132", "title": "The role of prostaglandins in the study of intestinal water and electrolyte transport in man.", "content": "The objective of this paper is to assess current knowledge on the pharmacologic and presumed physiologic effects of prostaglandins (PGs) on water and ion transport in the human intestine, from data in the literature and results of authors' studies. PGs, when administered intraluminally or intravenously, induce a profuse net secretion of water and ions into the jejunum or ileum; there is evidence that this effect is unrelated to changes in motility but due to a direct interaction of PGs with mucosal transport processes. Relations of PGs to cholera toxin, gastrointestinal hormones and adenylate cyclase-cyclic AMP system are reviewed. We propose to consider PGs as one of the most convenient model for studying intestinal secretion in vivo in man, in view of the rapid onset, magnitude, reversibility and reproducibility of their striking effect on mucosal transport.", "contents": "The role of prostaglandins in the study of intestinal water and electrolyte transport in man. The objective of this paper is to assess current knowledge on the pharmacologic and presumed physiologic effects of prostaglandins (PGs) on water and ion transport in the human intestine, from data in the literature and results of authors' studies. PGs, when administered intraluminally or intravenously, induce a profuse net secretion of water and ions into the jejunum or ileum; there is evidence that this effect is unrelated to changes in motility but due to a direct interaction of PGs with mucosal transport processes. Relations of PGs to cholera toxin, gastrointestinal hormones and adenylate cyclase-cyclic AMP system are reviewed. We propose to consider PGs as one of the most convenient model for studying intestinal secretion in vivo in man, in view of the rapid onset, magnitude, reversibility and reproducibility of their striking effect on mucosal transport."}
{"id": "PMID:212136", "title": "[Electron paramagnetic resonance study of the products of the reaction between nitrogen oxides and several organic compounds].", "content": "A method of electron paramagnetic resonance was applied to the study of a possibility of paramagnetic centres formation in the nitrogen oxide reaction with saturated and unsaturated fatty acids and aromatic amino acids. Several paramagnetic centres are formed in interaction of NO2 with oleic acid at 20 degrees C. Saturated fatty acids formed no paramagnetic centres in the reaction with NO2. NO formed no paramagnetic centres not only with butyric, palmitic, and stearic acids, but also with oleic acid. The capacity of NO2 to form paramagentic centres with tyrosine in its saturated solution was revealed. In  case of interaction between NO and NO2 with saturated phenylalanine and tryptophane solutions no formation of paramagnetic centres was observed. It is suggested that unsaturated fatty acids and tyrosine remnants of the membrane lipoprotein complexes could serve as peculiar targets with which NO2 interacted, and that formation of paramagnetic centres in the NO2 reaction with the mentioned substances was the primary act of the membrane damage.", "contents": "[Electron paramagnetic resonance study of the products of the reaction between nitrogen oxides and several organic compounds]. A method of electron paramagnetic resonance was applied to the study of a possibility of paramagnetic centres formation in the nitrogen oxide reaction with saturated and unsaturated fatty acids and aromatic amino acids. Several paramagnetic centres are formed in interaction of NO2 with oleic acid at 20 degrees C. Saturated fatty acids formed no paramagnetic centres in the reaction with NO2. NO formed no paramagnetic centres not only with butyric, palmitic, and stearic acids, but also with oleic acid. The capacity of NO2 to form paramagentic centres with tyrosine in its saturated solution was revealed. In  case of interaction between NO and NO2 with saturated phenylalanine and tryptophane solutions no formation of paramagnetic centres was observed. It is suggested that unsaturated fatty acids and tyrosine remnants of the membrane lipoprotein complexes could serve as peculiar targets with which NO2 interacted, and that formation of paramagnetic centres in the NO2 reaction with the mentioned substances was the primary act of the membrane damage."}
{"id": "PMID:212137", "title": "[Increase in the antiviral resistance of cells after treating them with messenger RNA for antiviral protein].", "content": "The authors studied antiviral resistance of murine cells L-929 following single introduction into them of homologous and heterologous informative RNA preparations for antiviral protein (i-RNA-AVP). As shown, in using homologous i-RVA-AVP preparations suppression of the virus production constituted 90--93%, and was stably traced in cell passage in the course of 1 1/2 months (observation period). Following cell contact with heterologous i-RNA-AVP preparations suppression the first 6 passages of the virus production constituted about 90%, rising by the 16th passage to 99.9%. The data obtained pointed to the possibility of stable increase of cell antiviral resistance with the aid of i-RNA-AVP, this could serve as a new effective method of nonspecific cell protection from the viruses.", "contents": "[Increase in the antiviral resistance of cells after treating them with messenger RNA for antiviral protein]. The authors studied antiviral resistance of murine cells L-929 following single introduction into them of homologous and heterologous informative RNA preparations for antiviral protein (i-RNA-AVP). As shown, in using homologous i-RVA-AVP preparations suppression of the virus production constituted 90--93%, and was stably traced in cell passage in the course of 1 1/2 months (observation period). Following cell contact with heterologous i-RNA-AVP preparations suppression the first 6 passages of the virus production constituted about 90%, rising by the 16th passage to 99.9%. The data obtained pointed to the possibility of stable increase of cell antiviral resistance with the aid of i-RNA-AVP, this could serve as a new effective method of nonspecific cell protection from the viruses."}
{"id": "PMID:212133", "title": "Induction of hyperlipemia by carbohydrate-rich fractions isolated from crude papain.", "content": "A hyperlipemia was obtained in rabbits injected intravenously with two carbohydrate-rich fractions isolated from crude papain dialyzate. The fractions have an approximative molecular weight of 15,000 and 5,000 daltons and contains 35% and 15% of sugars respectively. The hyperlipemia appears 20 hours after the injection and consists in a hypertriglyceridaemia as suggested by the enrichment of serum in very light lipoproteins of density about 1.006. Concomittantly a decrease of the post-heparin lipase activity (PHLA) of the plasma was observed. After a few days the hyperlipemia disappears and the PHLA returns to a normal value. It is suggested that the hypertriglyceridaemia can be due to an inhibitory effect of the injected fractions on the removal action of the lipases which are released into the blood by an heparin injection.", "contents": "Induction of hyperlipemia by carbohydrate-rich fractions isolated from crude papain. A hyperlipemia was obtained in rabbits injected intravenously with two carbohydrate-rich fractions isolated from crude papain dialyzate. The fractions have an approximative molecular weight of 15,000 and 5,000 daltons and contains 35% and 15% of sugars respectively. The hyperlipemia appears 20 hours after the injection and consists in a hypertriglyceridaemia as suggested by the enrichment of serum in very light lipoproteins of density about 1.006. Concomittantly a decrease of the post-heparin lipase activity (PHLA) of the plasma was observed. After a few days the hyperlipemia disappears and the PHLA returns to a normal value. It is suggested that the hypertriglyceridaemia can be due to an inhibitory effect of the injected fractions on the removal action of the lipases which are released into the blood by an heparin injection."}
{"id": "PMID:212138", "title": "[Reaction between dexamethasone-receptor complexes and isolated nuclei from Zajdela hepatoma and rat liver cells].", "content": "Temperature-activation of the hormone-receptor complex (HRC) was shown to be necessary to ensure its translocation from cytoplasm to nucleus both in the rat liver and hepatoma. Hepatoma nuclei bind 20 times less HRC derived from homologous hepatoma cytosol (0.15 pmol/mg DNA), but twice as much (5.6 pmol/mg DNA) of HRC from heterologous liver cytosol, as compared with the binding of HRC from normal liver cytosol by liver nuclei (3 pmol/mg DNA), Ka of HRC with the acceptor sites in hepatoma and liver nuclei were found to be practically of the same order of magnitude. The above findings suggest an inhibition of cytosol-nucleus translocation of HRC from the cytosol of hepatoma cells as a possible cause of the nonresponsiveness of the latter to the hormone.", "contents": "[Reaction between dexamethasone-receptor complexes and isolated nuclei from Zajdela hepatoma and rat liver cells]. Temperature-activation of the hormone-receptor complex (HRC) was shown to be necessary to ensure its translocation from cytoplasm to nucleus both in the rat liver and hepatoma. Hepatoma nuclei bind 20 times less HRC derived from homologous hepatoma cytosol (0.15 pmol/mg DNA), but twice as much (5.6 pmol/mg DNA) of HRC from heterologous liver cytosol, as compared with the binding of HRC from normal liver cytosol by liver nuclei (3 pmol/mg DNA), Ka of HRC with the acceptor sites in hepatoma and liver nuclei were found to be practically of the same order of magnitude. The above findings suggest an inhibition of cytosol-nucleus translocation of HRC from the cytosol of hepatoma cells as a possible cause of the nonresponsiveness of the latter to the hormone."}
{"id": "PMID:212139", "title": "[Mechanism of the inhibitory effect of BCG vaccine on specific antitumor immunity in Syrian hamsters].", "content": "The duration of inhibiting influence of BCG vaccine on specific antitumour immunity and possibility of SV40-induced resistance restoration in Syrian hamsters after the vaccination was studied. Antitumor immunity in animals immunized with SV40 virus and then inoculated with BCG was demonstrated to be abrogated one year after the vaccination. Reinoculation of the subjected to combined immunization animals with SV40 virus induced specific antitumour resistance in them again. The data presented may be interpreted as an argument favouring the cell-mediated nature of the phenomenon described.", "contents": "[Mechanism of the inhibitory effect of BCG vaccine on specific antitumor immunity in Syrian hamsters]. The duration of inhibiting influence of BCG vaccine on specific antitumour immunity and possibility of SV40-induced resistance restoration in Syrian hamsters after the vaccination was studied. Antitumor immunity in animals immunized with SV40 virus and then inoculated with BCG was demonstrated to be abrogated one year after the vaccination. Reinoculation of the subjected to combined immunization animals with SV40 virus induced specific antitumour resistance in them again. The data presented may be interpreted as an argument favouring the cell-mediated nature of the phenomenon described."}
{"id": "PMID:212140", "title": "[Specific variability in the number of cells with X-chromatin in short-term buccal epithelium cultures from women following exposure to hormones at different phases in their individual diurnal biorhythm].", "content": "Changes in the number of cells with X- and K-chromatin were studied in the buccal epithelium of 4 women in vivo for 29 h, every 2--4 h, and similarly in cultures (3 h) with and without any hormone: ACTH, insulin, thyroxin. The biorhythm of the cells with X-chromatin (established by Kanyuka in 1973) both in vivo and ie vitro within the range of from 44 to 340 0/00 per 24 h was confirmed; individual variability of the mean heterochromatin index value (X-HClm) was revealed in vitro with and without any hormones. Cell incubation with hormones at the time of minimal X-HCl in vivo led to increase in the number of cells with X-chromatin within 3 h from 50 to 240 0/00, whereas incubation at the time of maximal X-HCl in vivo--to reduction from 190 to 70 0/00. It is suggested that the specific response to the hormones is preceded by the nonspecific tissue response, determined by its condition at the time of action (by the individual X-HCl biorhythm phase) and realized in the systemic reconstruction of the number of cells at various mitotic cycle phases. Stereotypic reaction was expressed in the changes in character of the nuclear chromatin sondensation; these processes were reversible.", "contents": "[Specific variability in the number of cells with X-chromatin in short-term buccal epithelium cultures from women following exposure to hormones at different phases in their individual diurnal biorhythm]. Changes in the number of cells with X- and K-chromatin were studied in the buccal epithelium of 4 women in vivo for 29 h, every 2--4 h, and similarly in cultures (3 h) with and without any hormone: ACTH, insulin, thyroxin. The biorhythm of the cells with X-chromatin (established by Kanyuka in 1973) both in vivo and ie vitro within the range of from 44 to 340 0/00 per 24 h was confirmed; individual variability of the mean heterochromatin index value (X-HClm) was revealed in vitro with and without any hormones. Cell incubation with hormones at the time of minimal X-HCl in vivo led to increase in the number of cells with X-chromatin within 3 h from 50 to 240 0/00, whereas incubation at the time of maximal X-HCl in vivo--to reduction from 190 to 70 0/00. It is suggested that the specific response to the hormones is preceded by the nonspecific tissue response, determined by its condition at the time of action (by the individual X-HCl biorhythm phase) and realized in the systemic reconstruction of the number of cells at various mitotic cycle phases. Stereotypic reaction was expressed in the changes in character of the nuclear chromatin sondensation; these processes were reversible."}
{"id": "PMID:212141", "title": "Polyoma virus, as a model for viral skin carcinogenesis.", "content": "Polyoma virus is presented as the simplest model of transformation by a DNA virus. The three possible ways of virus/cell interaction are recalled: lytic infection, abortive infection and malignant transformation. Nuclear and surface antigenic modifications are also recalled as well as their possible correlation with the transformation mechanism. Lastly, in \"in vivo\" systems, we have tried to schematize the interactions of host and virus-induced tumour.", "contents": "Polyoma virus, as a model for viral skin carcinogenesis. Polyoma virus is presented as the simplest model of transformation by a DNA virus. The three possible ways of virus/cell interaction are recalled: lytic infection, abortive infection and malignant transformation. Nuclear and surface antigenic modifications are also recalled as well as their possible correlation with the transformation mechanism. Lastly, in \"in vivo\" systems, we have tried to schematize the interactions of host and virus-induced tumour."}
{"id": "PMID:212142", "title": "The human papillomaviruses.", "content": "Recent biochemical and serological studies have shown the existence of at least four distinct types of human papillomaviruses (HPVs) causing benign skin lesions. These viruses show hardly no antigenic relationships; their DNAs differ by their sensitivity to restriction endonucleases, and show little, if any, sequence homology, as detected by molecular hybridization using complementary RNAs transcribed in vitro. Data on the pathogenicity of HPVs are still incomplete but indicate that some types of benign skin lesions (plantar warts, common warts, flat warts) may be preferentially associated with some types of HPV. Most interesting is that epidermodysplasia verruciformis has been found associated with two types of virus, and that malignant conversion of some lesions has been observed in all the patients infected with one of them. This suggests that at least a HPV may have a higher oncogenic potential, as do rabbit (Shope) papillomavirus and bovine alimentary tract papillomavirus. Much remains to be known on human papilloma-viruses and further studies may lead to the characterization of additional types of HPVs, especially in genital condylomata acuminata and laryngeal papillomas whose malignant conversion, although rare, may be observed. Progress in this field has been and remains hampered by the lack of cell culture systems allowing replication of these highly host and tissue specific viruses, and by the widely variable virus content of the different human lesions known to be associated with a papillomavirus. Further studies are warranted by the possible role of these widespread and epitheliotropic viruses in the origin of some carcinomas in man.", "contents": "The human papillomaviruses. Recent biochemical and serological studies have shown the existence of at least four distinct types of human papillomaviruses (HPVs) causing benign skin lesions. These viruses show hardly no antigenic relationships; their DNAs differ by their sensitivity to restriction endonucleases, and show little, if any, sequence homology, as detected by molecular hybridization using complementary RNAs transcribed in vitro. Data on the pathogenicity of HPVs are still incomplete but indicate that some types of benign skin lesions (plantar warts, common warts, flat warts) may be preferentially associated with some types of HPV. Most interesting is that epidermodysplasia verruciformis has been found associated with two types of virus, and that malignant conversion of some lesions has been observed in all the patients infected with one of them. This suggests that at least a HPV may have a higher oncogenic potential, as do rabbit (Shope) papillomavirus and bovine alimentary tract papillomavirus. Much remains to be known on human papilloma-viruses and further studies may lead to the characterization of additional types of HPVs, especially in genital condylomata acuminata and laryngeal papillomas whose malignant conversion, although rare, may be observed. Progress in this field has been and remains hampered by the lack of cell culture systems allowing replication of these highly host and tissue specific viruses, and by the widely variable virus content of the different human lesions known to be associated with a papillomavirus. Further studies are warranted by the possible role of these widespread and epitheliotropic viruses in the origin of some carcinomas in man."}
{"id": "PMID:212143", "title": "Heterogeneity of human papilloma viruses.", "content": "Two types of human papilloma viruses (HPV-1 and HPV-4) were characterized, which show no relationship as far as the following criteria are concerned: the pattern of restriction enzyme fragments of their DNA, DNA-cRNA hybridization, and complement fixation with specific rabbit antisera. Furthermore, the molecular weights of the major proteins differed significantly. Both types of viruses could be isolated from plantar warts and from verrucae vulgares. This paper gives the molecular weights of the major proteins of a third type of HPV from skin warts, which reacts neither with HPV-1 nor with HPV-4 rabbit antiserum.", "contents": "Heterogeneity of human papilloma viruses. Two types of human papilloma viruses (HPV-1 and HPV-4) were characterized, which show no relationship as far as the following criteria are concerned: the pattern of restriction enzyme fragments of their DNA, DNA-cRNA hybridization, and complement fixation with specific rabbit antisera. Furthermore, the molecular weights of the major proteins differed significantly. Both types of viruses could be isolated from plantar warts and from verrucae vulgares. This paper gives the molecular weights of the major proteins of a third type of HPV from skin warts, which reacts neither with HPV-1 nor with HPV-4 rabbit antiserum."}
{"id": "PMID:212144", "title": "Epidermodysplasia verruciformis. An autosomal recessive disease characterized by viral warts and skin cancer. A model for viral oncogenesis.", "content": "EV is an autosomal recessive disease which usually begins in infancy or childhood, with an average age of onset of 9. Flat warts are most common, but pityriasis-like warts occur in approximately 75% of patients. Warts are disseminated and chronic. Cancer may develop as early as age 13; the average age of onset is 31. About 1/3 rd. of patients develop cancer of the skin usually multiple and in light-exposed areas. It may take only two years from wart to cancer, or many more years. The cancer is carcinoma-in-situ of the Bowenoid type or squamous cell carcinoma. Two deaths have occured by local invasion and only one metastasis has been reported. One patient died of Burkitt's lymphoma and another was reported to have disseminated reticulosis. 8% of the patients are mentally retarded. Humoral immunity is normal; cell mediated immunity is depressed in most patients. The gene defect in EV has not yet been uncovered.", "contents": "Epidermodysplasia verruciformis. An autosomal recessive disease characterized by viral warts and skin cancer. A model for viral oncogenesis. EV is an autosomal recessive disease which usually begins in infancy or childhood, with an average age of onset of 9. Flat warts are most common, but pityriasis-like warts occur in approximately 75% of patients. Warts are disseminated and chronic. Cancer may develop as early as age 13; the average age of onset is 31. About 1/3 rd. of patients develop cancer of the skin usually multiple and in light-exposed areas. It may take only two years from wart to cancer, or many more years. The cancer is carcinoma-in-situ of the Bowenoid type or squamous cell carcinoma. Two deaths have occured by local invasion and only one metastasis has been reported. One patient died of Burkitt's lymphoma and another was reported to have disseminated reticulosis. 8% of the patients are mentally retarded. Humoral immunity is normal; cell mediated immunity is depressed in most patients. The gene defect in EV has not yet been uncovered."}
{"id": "PMID:212145", "title": "Immunological studies in epidermodysplasia verruciformis.", "content": "Immunofluorescence and cell mediated immunity studies have been performed in 14 cases of epidermodysplasia verruciformis (EV), 3 of those abortive or regressing in members of the families of the patients with EV. Two different types of human papillomavirus (HPV)--HPV3 and HPV4--have been found in cases of EV. HPV3 was detected also in flat warts without features of EV. There was no cross-reactivity between these two viruses, neither with HPV1 responsible for plantar warts nor with HPV2 inducing common warts. There was a relationship between the type of HPV and the clinical picture of EV as well as the malignant transformation, namely HPV4 has been found to be more oncogenic. Cell mediated immunity (CMI) seems to be an important factor because it was depressed in a vast majority of active cases and preserved in regressing and abortive cases (in the members of the families of EV patients). However, low CMI has been found in EV cases infected with HPV3 and in persistent flat warts also due to HPV3, which did not undergo malignant transformation. In contrast, in a case of EV due to HPV4 a malignant transformation occured in spite of still preserved, although lowered CMI. Various human papillomaviruses seem to differ in their oncogenic potential. HPV1 responsible for plantar warts, and HPV2 for common warts have no evident oncogenic potential, HPV3 inducing both EV and flat warts has a low oncogenicity, whereas HPV4 inducing some cases of EV seems more oncogenic.", "contents": "Immunological studies in epidermodysplasia verruciformis. Immunofluorescence and cell mediated immunity studies have been performed in 14 cases of epidermodysplasia verruciformis (EV), 3 of those abortive or regressing in members of the families of the patients with EV. Two different types of human papillomavirus (HPV)--HPV3 and HPV4--have been found in cases of EV. HPV3 was detected also in flat warts without features of EV. There was no cross-reactivity between these two viruses, neither with HPV1 responsible for plantar warts nor with HPV2 inducing common warts. There was a relationship between the type of HPV and the clinical picture of EV as well as the malignant transformation, namely HPV4 has been found to be more oncogenic. Cell mediated immunity (CMI) seems to be an important factor because it was depressed in a vast majority of active cases and preserved in regressing and abortive cases (in the members of the families of EV patients). However, low CMI has been found in EV cases infected with HPV3 and in persistent flat warts also due to HPV3, which did not undergo malignant transformation. In contrast, in a case of EV due to HPV4 a malignant transformation occured in spite of still preserved, although lowered CMI. Various human papillomaviruses seem to differ in their oncogenic potential. HPV1 responsible for plantar warts, and HPV2 for common warts have no evident oncogenic potential, HPV3 inducing both EV and flat warts has a low oncogenicity, whereas HPV4 inducing some cases of EV seems more oncogenic."}
{"id": "PMID:212146", "title": "Transformation of warts to malignancy in alimentary carcinoma in cattle.", "content": "There is a high incidence of alimentary carcinoma in beef cattle in the highland areas of Britain. Evidence is presented to shown that this is associated with the presence of bracken fern on high incidence farms and that many of the carcinomas arise in pre-existing virus-induced papillomas. Papillomas are much commoner and occur in greater numbers in animals of all ages on the cancer farms as compared to lowland cattle. Papillomas are found in all ages of cattle; carcinomas have only been seen in cows over 6 years of age. The virus has been isolated, visualized and purified; it produces papillomas when inoculated into the alimentary tract and skin.", "contents": "Transformation of warts to malignancy in alimentary carcinoma in cattle. There is a high incidence of alimentary carcinoma in beef cattle in the highland areas of Britain. Evidence is presented to shown that this is associated with the presence of bracken fern on high incidence farms and that many of the carcinomas arise in pre-existing virus-induced papillomas. Papillomas are much commoner and occur in greater numbers in animals of all ages on the cancer farms as compared to lowland cattle. Papillomas are found in all ages of cattle; carcinomas have only been seen in cows over 6 years of age. The virus has been isolated, visualized and purified; it produces papillomas when inoculated into the alimentary tract and skin."}
{"id": "PMID:212147", "title": "Interactions of Shope papilloma virus with some other DNA viruses.", "content": "The interactions of Shope papilloma virus (SPV) with primate and rabbit cells in tissue culture have been investigated. The rabbit cell cultures were derived from normal epidermis, from SPV-infected epidermis, from SPV-induced papillomas, and from an SPV-associated carcinoma. None of these cell cultures, whether infected in vitro with SPV or derived from tissues infected in vivo, ever produced infectious SPV or even detectable viral antigens. Some other DNA viruses behaved differently in cells which had been in previous contact with SPV either in vitro or in vivo. Adenovirus type 5 multiplies better in human cells infected 24 h previously with SPV than in the untreated controls. The production of infectious virions of either herpes simplex virus or Shope fibroma virus is reduced in cells derived from SPV-induced papillomas or carcinoma, due, apparently, to a defect in viral maturation. Of the rabbit cells, only those derived from in vivo infected tissue, or those previously infected in vitro with SPV, could be transformed by SV40. The rabbit cell lines derived from papillomas or carcinoma differed from their counterparts derived either from normal epidermis or from tissue infected 24 hrs before biopsy, in their karyotype, and in their ability to grow in soft agar. Similar karyotypic alterations were induced in cells derived from healthy epidermis by infection in vitro with SPV.", "contents": "Interactions of Shope papilloma virus with some other DNA viruses. The interactions of Shope papilloma virus (SPV) with primate and rabbit cells in tissue culture have been investigated. The rabbit cell cultures were derived from normal epidermis, from SPV-infected epidermis, from SPV-induced papillomas, and from an SPV-associated carcinoma. None of these cell cultures, whether infected in vitro with SPV or derived from tissues infected in vivo, ever produced infectious SPV or even detectable viral antigens. Some other DNA viruses behaved differently in cells which had been in previous contact with SPV either in vitro or in vivo. Adenovirus type 5 multiplies better in human cells infected 24 h previously with SPV than in the untreated controls. The production of infectious virions of either herpes simplex virus or Shope fibroma virus is reduced in cells derived from SPV-induced papillomas or carcinoma, due, apparently, to a defect in viral maturation. Of the rabbit cells, only those derived from in vivo infected tissue, or those previously infected in vitro with SPV, could be transformed by SV40. The rabbit cell lines derived from papillomas or carcinoma differed from their counterparts derived either from normal epidermis or from tissue infected 24 hrs before biopsy, in their karyotype, and in their ability to grow in soft agar. Similar karyotypic alterations were induced in cells derived from healthy epidermis by infection in vitro with SPV."}
{"id": "PMID:212149", "title": "The effects of release and depletion of endogenous noradrenaline on the transmission of impulses in the mouse vas deferens.", "content": "1 The effects of endogenous noradrenaline released by tyramine and the influence of depletion of the tissue noradrenaline with reserpine and/or alpha-methyl-p-tyrosine on the twitch responses of the field-stimulated mouse vas deferens have been studied.2 Tyramine (10-40 muM) inhibited the twitch responses to field stimulation and failed to produce a contraction. The inhibition decreased as the rate of stimulation increased.3 The inhibition produced by tyramine was antagonized by cocaine (10 muM) and by yohimbine (10 nM), which indicated that it was produced by released noradrenaline acting on presynaptic alpha-adrenoceptors.4 Depletion of the tissue noradrenaline by 39% by blockade of the synthesis of noradrenaline with alpha-methyl-p-tyrosine, was without effect on the twitch response but it reduced the inhibitory effect of tyramine.5 Depletion of the tissue noradrenaline by 96.5% with reserpine alone and by 99.4%, with a combination of reserpine and alpha-methyl-p-tyrosine, reduced the twitch responses by approximately 66% and virtually abolished the inhibition produced by tyramine. It also increased the rate of decline of the responses when the tissue was continuously stimulated. The remaining twitch was not antagonized by phenoxybenzamine (15 muM).6 Residual twitches were bigger in tissues depleted by 99.4% than in those depleted by only 96.5%. This difference was eliminated in the presence of yohimbine (128 nM).7 It is concluded that inhibition of the twitch responses by tyramine is produced by stimulation of presynaptic alpha-adrenoceptors and that the twitch response is associated with stimulation of the sympathetic neurone, but that it is not mediated by postsynaptic alpha-adrenoceptors.", "contents": "The effects of release and depletion of endogenous noradrenaline on the transmission of impulses in the mouse vas deferens. 1 The effects of endogenous noradrenaline released by tyramine and the influence of depletion of the tissue noradrenaline with reserpine and/or alpha-methyl-p-tyrosine on the twitch responses of the field-stimulated mouse vas deferens have been studied.2 Tyramine (10-40 muM) inhibited the twitch responses to field stimulation and failed to produce a contraction. The inhibition decreased as the rate of stimulation increased.3 The inhibition produced by tyramine was antagonized by cocaine (10 muM) and by yohimbine (10 nM), which indicated that it was produced by released noradrenaline acting on presynaptic alpha-adrenoceptors.4 Depletion of the tissue noradrenaline by 39% by blockade of the synthesis of noradrenaline with alpha-methyl-p-tyrosine, was without effect on the twitch response but it reduced the inhibitory effect of tyramine.5 Depletion of the tissue noradrenaline by 96.5% with reserpine alone and by 99.4%, with a combination of reserpine and alpha-methyl-p-tyrosine, reduced the twitch responses by approximately 66% and virtually abolished the inhibition produced by tyramine. It also increased the rate of decline of the responses when the tissue was continuously stimulated. The remaining twitch was not antagonized by phenoxybenzamine (15 muM).6 Residual twitches were bigger in tissues depleted by 99.4% than in those depleted by only 96.5%. This difference was eliminated in the presence of yohimbine (128 nM).7 It is concluded that inhibition of the twitch responses by tyramine is produced by stimulation of presynaptic alpha-adrenoceptors and that the twitch response is associated with stimulation of the sympathetic neurone, but that it is not mediated by postsynaptic alpha-adrenoceptors."}
{"id": "PMID:212150", "title": "The role of beta1- and beta2-adrenoceptors in the inhibition of gastric acid secretion in the dog.", "content": "1. Characterization of the beta-adrenoceptors mediating inhibition of gastric acid secretion in the conscious Heidenhain pouch dog has been investigated by determination of the effects of propranolol, (+)-propranolol, practolol and H35/25 on salbutamol and isoprenaline-induced inhibition of gastric acid secretion. 2. The gastric antisecretory effect of salbutamol was significantly blocked by propranolol and H35/25 but not by practolol or (+)-propranolol. The effect of isoprenaline was significantly blocked by propranolol and practolol but not by H35/25 or (+)-propranolol. 3. It is concluded that both beta1- and beta2-adrenoceptors can mediate inhibition of pentagastrin-induced gastric secretion in conscious dogs with a Heidenhain pouch. Salbutamol exerts its antisecretory effect through beta2-adrenoceptors, whereas isoprenaline mediates its effects primarily through beta1-adrenoceptors. 4. The results are discussed with regard to the sub-classification of beta-adrenoceptors and to the possible role of adrenoceptors in the physiological control of gastric secretion. 5. In this study it is concluded that the tachycardia induced by isoprenaline or salbutamol is mediated primarily through reflexes activated by beta2-adrenoceptor mediated vasodilatation.", "contents": "The role of beta1- and beta2-adrenoceptors in the inhibition of gastric acid secretion in the dog. 1. Characterization of the beta-adrenoceptors mediating inhibition of gastric acid secretion in the conscious Heidenhain pouch dog has been investigated by determination of the effects of propranolol, (+)-propranolol, practolol and H35/25 on salbutamol and isoprenaline-induced inhibition of gastric acid secretion. 2. The gastric antisecretory effect of salbutamol was significantly blocked by propranolol and H35/25 but not by practolol or (+)-propranolol. The effect of isoprenaline was significantly blocked by propranolol and practolol but not by H35/25 or (+)-propranolol. 3. It is concluded that both beta1- and beta2-adrenoceptors can mediate inhibition of pentagastrin-induced gastric secretion in conscious dogs with a Heidenhain pouch. Salbutamol exerts its antisecretory effect through beta2-adrenoceptors, whereas isoprenaline mediates its effects primarily through beta1-adrenoceptors. 4. The results are discussed with regard to the sub-classification of beta-adrenoceptors and to the possible role of adrenoceptors in the physiological control of gastric secretion. 5. In this study it is concluded that the tachycardia induced by isoprenaline or salbutamol is mediated primarily through reflexes activated by beta2-adrenoceptor mediated vasodilatation."}
{"id": "PMID:212151", "title": "Central actions of benzodiazepines: general introduction.", "content": "After a brief review of the characteristic somatic and psychotropic effects of benzodiazepines evidence is presented which supports a specific facilitatory action of these drugs on GABA ergic synapses within the mammalian central nervous system. Benzodiazepines enhance presynaptic inhibition in the spinal cord and dorsal column nuclei as well as postsynaptic inhibition in dorsal column nuclei, hippocampus, hypothalamus, cerebral cortex, cerebellar cortex, which are all examples of recurrent and collateral inhibition mediated by GABA ergic intrinsic neurones. In addition, the compounds also enhance the inhibitory effect of GABA ergic long projection neurones in the substantia nigra and the lateral vestibular nucleus of Deiters. Several problems remain to be solved, such as the exact site at which benzodiazepines initiate their action (pre-synaptically at GABA ergic nerve endings or postsynaptically at the target cells) and the possible existence of endogenous ligands for the benzodiazepine receptor. Some suspected implications which studies on benzodiazepine binding sites could have for a deeper understanding of the mode of action of these drugs are discussed.", "contents": "Central actions of benzodiazepines: general introduction. After a brief review of the characteristic somatic and psychotropic effects of benzodiazepines evidence is presented which supports a specific facilitatory action of these drugs on GABA ergic synapses within the mammalian central nervous system. Benzodiazepines enhance presynaptic inhibition in the spinal cord and dorsal column nuclei as well as postsynaptic inhibition in dorsal column nuclei, hippocampus, hypothalamus, cerebral cortex, cerebellar cortex, which are all examples of recurrent and collateral inhibition mediated by GABA ergic intrinsic neurones. In addition, the compounds also enhance the inhibitory effect of GABA ergic long projection neurones in the substantia nigra and the lateral vestibular nucleus of Deiters. Several problems remain to be solved, such as the exact site at which benzodiazepines initiate their action (pre-synaptically at GABA ergic nerve endings or postsynaptically at the target cells) and the possible existence of endogenous ligands for the benzodiazepine receptor. Some suspected implications which studies on benzodiazepine binding sites could have for a deeper understanding of the mode of action of these drugs are discussed."}
{"id": "PMID:212152", "title": "Molecular mechanisms mediating the action of diazepam on GABA receptors.", "content": "Two types of crude synaptic membranes have been prepared which differ in their kinetic properties to bind 3H-GABA in a Na+-free medium. One type (B) has one type of receptor (affinity or KD about 0.2 micrometer), the other type (A) has two populations of receptors which have a high (0.16 micrometer) and a low ((.02 micrometer) KD for GABA binding. This difference is due to the presence of a selective endogenous inhibitor of the high affinity receptor for GABA, a thermostable protein of about 15,000 molecular weight. Inhibitor action is counteracted by diazepam (7 X 10(-7) M), competitively. Clonazepam is more active but chlordiazepoxide is less active than diazepam. Two enantiomers of a benzodiazepine were studied. One of them is endowed with anxiolytic activity and nullifies the action of the endogenous inhibitor on high affinity GABA binding, the other is devoid of anxiolytic activity and is inactive against the inhibitor. The endogenous protein inhibitor also competitively blocks the high affinity binding of 3H-diazepam to Type A membranes. It is concluded that the endogenous inhibitor and diazepam act on the same receptor; and suggested that the endogenous inhibitor may be the natural ligand for the brain receptors that bind benzodiazepines with high affinity.", "contents": "Molecular mechanisms mediating the action of diazepam on GABA receptors. Two types of crude synaptic membranes have been prepared which differ in their kinetic properties to bind 3H-GABA in a Na+-free medium. One type (B) has one type of receptor (affinity or KD about 0.2 micrometer), the other type (A) has two populations of receptors which have a high (0.16 micrometer) and a low ((.02 micrometer) KD for GABA binding. This difference is due to the presence of a selective endogenous inhibitor of the high affinity receptor for GABA, a thermostable protein of about 15,000 molecular weight. Inhibitor action is counteracted by diazepam (7 X 10(-7) M), competitively. Clonazepam is more active but chlordiazepoxide is less active than diazepam. Two enantiomers of a benzodiazepine were studied. One of them is endowed with anxiolytic activity and nullifies the action of the endogenous inhibitor on high affinity GABA binding, the other is devoid of anxiolytic activity and is inactive against the inhibitor. The endogenous protein inhibitor also competitively blocks the high affinity binding of 3H-diazepam to Type A membranes. It is concluded that the endogenous inhibitor and diazepam act on the same receptor; and suggested that the endogenous inhibitor may be the natural ligand for the brain receptors that bind benzodiazepines with high affinity."}
{"id": "PMID:212153", "title": "The benzodiazepine receptor in normal and pathological human brain.", "content": "Benzodiazepines bind with high affinity to a specific benzodiazepine receptor, which occurs exclusively in the central nervous system. The affinity of various benzodiazepines to the receptor closely parallels their pharmacological and therapeutic potency. Binding to the receptor is stereospecific. The receptor is mainly localized in the synaptic membrane fraction and has its highest density in cortical areas of the brain. In Huntington's chorea a decrease in benzodiazepine receptor binding is found in caudate nucleus and putamen, which, at least in putamen, is due to a loss of benzodiazepine receptors apparently located on GABA neurones, which degenerate in Huntington's chorea. The loss of benzodiazepine receptors might explain why the ameliorative effects of benzodiazepines in the early stages of the disease are not sustained in the later stages.", "contents": "The benzodiazepine receptor in normal and pathological human brain. Benzodiazepines bind with high affinity to a specific benzodiazepine receptor, which occurs exclusively in the central nervous system. The affinity of various benzodiazepines to the receptor closely parallels their pharmacological and therapeutic potency. Binding to the receptor is stereospecific. The receptor is mainly localized in the synaptic membrane fraction and has its highest density in cortical areas of the brain. In Huntington's chorea a decrease in benzodiazepine receptor binding is found in caudate nucleus and putamen, which, at least in putamen, is due to a loss of benzodiazepine receptors apparently located on GABA neurones, which degenerate in Huntington's chorea. The loss of benzodiazepine receptors might explain why the ameliorative effects of benzodiazepines in the early stages of the disease are not sustained in the later stages."}
{"id": "PMID:212162", "title": "Excitability increase of neurons in olfactory cortex slices of the guinea pig after penicillin administration.", "content": "The mechanism underlying the effects of penicillin on slices of the olfactory cortex of the guinea pig was examined. In a previous report it was shown that penicillin increases the amplitude of the presynaptic action potential, the population EPSP and, more strongly, the population responses of the postsynaptic cells. Moreover, the postsynaptic population responses increased in number and suggested strong repetitive firing. These results were confirmed in the present study. Analysis of stimulus-response relationships suggested that the enhancement of the postsynaptic response was due to an increase in excitability of the postsynaptic neurons by penicillin. The amplitude changes of the presynaptic action potential and the EPSP were probably largely, if not completely, due to an increase in resistance of the bathing fluid. It was found that the changes in population responses paralleled to a large extent changes in cell discharge. In addition, penicillin was found to induce spontaneous firing of the postsynaptic cells. The changes in cell discharge were consistent with an increase in excitability of the postsynaptic cells.", "contents": "Excitability increase of neurons in olfactory cortex slices of the guinea pig after penicillin administration. The mechanism underlying the effects of penicillin on slices of the olfactory cortex of the guinea pig was examined. In a previous report it was shown that penicillin increases the amplitude of the presynaptic action potential, the population EPSP and, more strongly, the population responses of the postsynaptic cells. Moreover, the postsynaptic population responses increased in number and suggested strong repetitive firing. These results were confirmed in the present study. Analysis of stimulus-response relationships suggested that the enhancement of the postsynaptic response was due to an increase in excitability of the postsynaptic neurons by penicillin. The amplitude changes of the presynaptic action potential and the EPSP were probably largely, if not completely, due to an increase in resistance of the bathing fluid. It was found that the changes in population responses paralleled to a large extent changes in cell discharge. In addition, penicillin was found to induce spontaneous firing of the postsynaptic cells. The changes in cell discharge were consistent with an increase in excitability of the postsynaptic cells."}
{"id": "PMID:212166", "title": "Some actions of catechol on synaptic transmission in the isolated spinal cord of the frog.", "content": "The isolated frog spinal cord was used to investigate the synaptic effects of the convulsant agent catechol. Addition of the compound to the superfusate consistently enhanced orthodromic reflex activity recorded from ventral roots and augmented primary afferent depolarization. Concomitantly catechol altered the polarization changes produced in ventral and dorsal roots by putative neurotransmitter amino acids when these compounds were applied in Mg2+-containing Ringer. Catechol reduced the hyperpolarizations induced in motoneurons by the neutral amino acids, GABA, beta-alanine, taurine and glycine, but did not affect the depolarizations produced by the dicarboxylic amino acids, L-glutamate and L-aspartate. In contrast, catechol increased the dorsal root depolarizations elicited by both neutral and dicarboxylic amino acids and also the depolarizations produced by elevated potassium concentrations. Catechol did not bring about significant changes in the passive electrical properties of motoneurons or dorsal root fibers. In addition, it did not alter either the high affinity uptake or the depolarization-evoked release of tritiated GABA, glycine, L-glutamate and L-aspartate. It appears that the postsynaptic actions of catechol explain its ability to enhance spinal reflexes.", "contents": "Some actions of catechol on synaptic transmission in the isolated spinal cord of the frog. The isolated frog spinal cord was used to investigate the synaptic effects of the convulsant agent catechol. Addition of the compound to the superfusate consistently enhanced orthodromic reflex activity recorded from ventral roots and augmented primary afferent depolarization. Concomitantly catechol altered the polarization changes produced in ventral and dorsal roots by putative neurotransmitter amino acids when these compounds were applied in Mg2+-containing Ringer. Catechol reduced the hyperpolarizations induced in motoneurons by the neutral amino acids, GABA, beta-alanine, taurine and glycine, but did not affect the depolarizations produced by the dicarboxylic amino acids, L-glutamate and L-aspartate. In contrast, catechol increased the dorsal root depolarizations elicited by both neutral and dicarboxylic amino acids and also the depolarizations produced by elevated potassium concentrations. Catechol did not bring about significant changes in the passive electrical properties of motoneurons or dorsal root fibers. In addition, it did not alter either the high affinity uptake or the depolarization-evoked release of tritiated GABA, glycine, L-glutamate and L-aspartate. It appears that the postsynaptic actions of catechol explain its ability to enhance spinal reflexes."}
{"id": "PMID:212168", "title": "F-wave and cervical somatosensory response conduction from the seventh cervical spinous process to cortex in multiple sclerosis.", "content": "Transit (conduction) times from the wrist to the seventh cervical spinous process (C7) were measured by using the F-wave response (TA) and the cervical somatosensory response (SEPC). The mean values obtained in 25 controls were 10.1 +/- 0.9 s-3 and 10.9 +/- 1.0 s-1 respectively. The 0.8 +/- 1.0 s-3 difference between the two methods represents central delay of SEPC, possibly at the level of the dorsal root ganglion. The mean onset latency of the cortical somatosensory response (SEPA) evoked by median nerve stimulation in the same subjects was 15.5 +/- 1.0 s-3. Transit time from C7 to the cortex (TB) given by either SEPA - TA or SEPA - SEPC - 0.8, where 0.8 is the necessary corrective factor for central delay of SEPC, WAS 5.3 +/- 1.0 S-3. These techniques were applied to 10 patients suspected of having multiple sclerosis, but without clinical evidence of involvement above C7. Six of the 10 cases showed prolongation of TB. In 4 of these, this could only be calculated by the F-wave method since SEPC was absent. It is concluded that transit times derived from either the F-wave or SEPC are equally valid and interchangeable. The absence of one response allows for its replacement by the other.", "contents": "F-wave and cervical somatosensory response conduction from the seventh cervical spinous process to cortex in multiple sclerosis. Transit (conduction) times from the wrist to the seventh cervical spinous process (C7) were measured by using the F-wave response (TA) and the cervical somatosensory response (SEPC). The mean values obtained in 25 controls were 10.1 +/- 0.9 s-3 and 10.9 +/- 1.0 s-1 respectively. The 0.8 +/- 1.0 s-3 difference between the two methods represents central delay of SEPC, possibly at the level of the dorsal root ganglion. The mean onset latency of the cortical somatosensory response (SEPA) evoked by median nerve stimulation in the same subjects was 15.5 +/- 1.0 s-3. Transit time from C7 to the cortex (TB) given by either SEPA - TA or SEPA - SEPC - 0.8, where 0.8 is the necessary corrective factor for central delay of SEPC, WAS 5.3 +/- 1.0 S-3. These techniques were applied to 10 patients suspected of having multiple sclerosis, but without clinical evidence of involvement above C7. Six of the 10 cases showed prolongation of TB. In 4 of these, this could only be calculated by the F-wave method since SEPC was absent. It is concluded that transit times derived from either the F-wave or SEPC are equally valid and interchangeable. The absence of one response allows for its replacement by the other."}
{"id": "PMID:212169", "title": "Mucin embolism to cerebral arteries: a fatal complication of carcinoma of the breast.", "content": "The case is reported of a woman with a mucin producing lobular carcinoma of the breast with metastases to many bone sites, whose terminal neurological illness was the result, not of cerebral metastases, but of cerebral infarcts. These were caused by emboli of mucin and emulsified fat, originating in bone metastases. The pathogenesis of this embolism is compared with that of traumatic fat embolism. Attention is drawn to this process because emboli of this type have never been reported and because this distant nonmetastatic effect of carcinoma may have been overlooked in other cases. It is suggested that this mechanism should be considered in the diagnosis of otherwise obscure cerebral infarction.", "contents": "Mucin embolism to cerebral arteries: a fatal complication of carcinoma of the breast. The case is reported of a woman with a mucin producing lobular carcinoma of the breast with metastases to many bone sites, whose terminal neurological illness was the result, not of cerebral metastases, but of cerebral infarcts. These were caused by emboli of mucin and emulsified fat, originating in bone metastases. The pathogenesis of this embolism is compared with that of traumatic fat embolism. Attention is drawn to this process because emboli of this type have never been reported and because this distant nonmetastatic effect of carcinoma may have been overlooked in other cases. It is suggested that this mechanism should be considered in the diagnosis of otherwise obscure cerebral infarction."}
{"id": "PMID:212173", "title": "Human colon tumors: enzymic and histological characteristics.", "content": "In samples of colonic adenocarcinomas, the mean activities of thymidine kinase, glucose-6-phosphate dehydrogenase, phosphoserine phosphatase and pyrroline-5-carboxylate reductase were several fold higher than those of nonneoplastic colon. The presence of considerable, cold labile pyrroline-5-carboxylate reductase activity provided an additional criterion for distinguishing tumors from the control tissue. Deviations from the pattern of enzymes in normal colon were much more pronounced in the five moderately well-differentiated than in the single well-differentiated adenocarcinoma.", "contents": "Human colon tumors: enzymic and histological characteristics. In samples of colonic adenocarcinomas, the mean activities of thymidine kinase, glucose-6-phosphate dehydrogenase, phosphoserine phosphatase and pyrroline-5-carboxylate reductase were several fold higher than those of nonneoplastic colon. The presence of considerable, cold labile pyrroline-5-carboxylate reductase activity provided an additional criterion for distinguishing tumors from the control tissue. Deviations from the pattern of enzymes in normal colon were much more pronounced in the five moderately well-differentiated than in the single well-differentiated adenocarcinoma."}
{"id": "PMID:212174", "title": "Ultrastructural observations in pleomorphic liposarcoma.", "content": "An ultrastructural study of pleomorphic liposarcoma with an unusual clinical presentation is described. A 69-year-old Caucasian female presented with recurrent superficial phlebitis of left leg, which responded only partially to conventional therapy. Following investigations, a mass was excised. Diagnosis of pleomorphic liposarcoma was made on microscopic examination. Numerous lipid droplets in the cytoplasm and often within intranuclear extensions of cytoplasm were seen on oil red O stain of frozen sections. Ultrastructural features are quite distinctive. The cells varied from small to often large pleomorphic cells with numerous lipid spaces without limiting membrane, large pleomorphic nuclei, and an abundance of cytoplasmic organelles. Centrioles were very prominent, in close proximity to nuclei, and collections of autophagocytic inclusions. Intercellular collagen was immature and scant. These features are compared to ultrastructural features of malignant fibrous histiocytoma, pleomorphic rhabdomyosarcoma, and cardiac myxoma, indicating that ultrastructural features are distinctive and help differentiate similar soft tissue tumors.", "contents": "Ultrastructural observations in pleomorphic liposarcoma. An ultrastructural study of pleomorphic liposarcoma with an unusual clinical presentation is described. A 69-year-old Caucasian female presented with recurrent superficial phlebitis of left leg, which responded only partially to conventional therapy. Following investigations, a mass was excised. Diagnosis of pleomorphic liposarcoma was made on microscopic examination. Numerous lipid droplets in the cytoplasm and often within intranuclear extensions of cytoplasm were seen on oil red O stain of frozen sections. Ultrastructural features are quite distinctive. The cells varied from small to often large pleomorphic cells with numerous lipid spaces without limiting membrane, large pleomorphic nuclei, and an abundance of cytoplasmic organelles. Centrioles were very prominent, in close proximity to nuclei, and collections of autophagocytic inclusions. Intercellular collagen was immature and scant. These features are compared to ultrastructural features of malignant fibrous histiocytoma, pleomorphic rhabdomyosarcoma, and cardiac myxoma, indicating that ultrastructural features are distinctive and help differentiate similar soft tissue tumors."}
{"id": "PMID:212175", "title": "Trace element concentrations in renal cell carcinoma.", "content": "Cadmium, zinc, copper levels and zinc-copper, zinc-bromine, iorn-zinc, iron-copper and iron-bromine ratios are measured in neoplastic and normal kidney samples from humans by the particle induced X-ray emission analysis (PIXE) technique. It is found that cadmium which is normally present in the tubular cells of kidney is not detectable in tumor samples. It is also observed that the zinc-copper ratios in all neoplastic kidney tissues are decreased, but this observation cannot be extended to other element ratios.", "contents": "Trace element concentrations in renal cell carcinoma. Cadmium, zinc, copper levels and zinc-copper, zinc-bromine, iorn-zinc, iron-copper and iron-bromine ratios are measured in neoplastic and normal kidney samples from humans by the particle induced X-ray emission analysis (PIXE) technique. It is found that cadmium which is normally present in the tubular cells of kidney is not detectable in tumor samples. It is also observed that the zinc-copper ratios in all neoplastic kidney tissues are decreased, but this observation cannot be extended to other element ratios."}
{"id": "PMID:212176", "title": "Retroperitoneal fibrohistiocytic tumors in children: report of five cases.", "content": "Five rare retroperitoneal fibrohistiocytic tumors of children are described mainly in reference to the pathological aspects. A more detailed description is given of a retroperitoneal xanthogranuloma, including an ultrastructural study. This case is particularly interesting for its rapid transformation into a fibroxanthosarcoma. The other cases include two fibroxanthosarcomas, a storiform fibrous xanthoma, and a malignant histiocytoma. The most difficult points in the recognition and in the differential diagnosis of these tumors are discussed, and emphasis is placed on some interesting pathological features. Prognosis of such tumors appears difficult to assess from our series since two patients died in the immediate postoperative period, one died one and a half years after the discovery of the tumor, and two are alive and well, but with a short follow-up.", "contents": "Retroperitoneal fibrohistiocytic tumors in children: report of five cases. Five rare retroperitoneal fibrohistiocytic tumors of children are described mainly in reference to the pathological aspects. A more detailed description is given of a retroperitoneal xanthogranuloma, including an ultrastructural study. This case is particularly interesting for its rapid transformation into a fibroxanthosarcoma. The other cases include two fibroxanthosarcomas, a storiform fibrous xanthoma, and a malignant histiocytoma. The most difficult points in the recognition and in the differential diagnosis of these tumors are discussed, and emphasis is placed on some interesting pathological features. Prognosis of such tumors appears difficult to assess from our series since two patients died in the immediate postoperative period, one died one and a half years after the discovery of the tumor, and two are alive and well, but with a short follow-up."}
{"id": "PMID:212179", "title": "Treatment of transplanted murine tumors with an oncolytic virus and cyclophosphamide.", "content": "Effective treatment of transplanted murine mammary tumors with an oncolytic virus and cyclophosphamide is reported. The oncolytic virus was cultured initially from a murine ascites tumor that had undergone \"spontaneous\" regression. This virus used alone causes rapid lysis of ascites tumors, but successful treatment of solid tumors requires the addition of cyclophosphamide. The virus must be injected directly into the tumor. The virus causes no detectable disease in mice even when administered in conjunction with cyclophosphamide. Fluorescent antibody techniques revealed that all A/S stock mice have antibody against cells infected with this virus.", "contents": "Treatment of transplanted murine tumors with an oncolytic virus and cyclophosphamide. Effective treatment of transplanted murine mammary tumors with an oncolytic virus and cyclophosphamide is reported. The oncolytic virus was cultured initially from a murine ascites tumor that had undergone \"spontaneous\" regression. This virus used alone causes rapid lysis of ascites tumors, but successful treatment of solid tumors requires the addition of cyclophosphamide. The virus must be injected directly into the tumor. The virus causes no detectable disease in mice even when administered in conjunction with cyclophosphamide. Fluorescent antibody techniques revealed that all A/S stock mice have antibody against cells infected with this virus."}
{"id": "PMID:212180", "title": "Growth of a human breast cancer cell line in serum-free hormone-supplemented medium.", "content": "ZR-75-1, a human breast cancer cell line, has been grown in hormone-supplemented medium without serum. The factors required for optimal growth include 17beta-estradiol, insulin, transferrin, dexamethasone, and L-triiodothyronine. If estradiol, insulin, or L-triiodothyronine is omitted, cells cease division within 7 days, but viability is retained for at least 14 days. Omission of transferrin leads to cell death within 7 days. The cells have been continuously maintained in this environment without morphological alteration or cessation of growth for more than 5 months. Addition of the anti-estrogen, Tamoxifen (10(-6) M), inhibited cells below the growth rate seen when estradiol was omitted from the medium, even when Tamoxifen was added 4 days and two medium changes after the removal of estradiol from the medium, thus suggesting an action of Tamoxifen which may be independent of competition with estradiol. The availability of a human breast cancer cell line that can be propagated in hormone-supplemented medium without serum should aid in the study of the mechanisms by which hormones effect cell growth.", "contents": "Growth of a human breast cancer cell line in serum-free hormone-supplemented medium. ZR-75-1, a human breast cancer cell line, has been grown in hormone-supplemented medium without serum. The factors required for optimal growth include 17beta-estradiol, insulin, transferrin, dexamethasone, and L-triiodothyronine. If estradiol, insulin, or L-triiodothyronine is omitted, cells cease division within 7 days, but viability is retained for at least 14 days. Omission of transferrin leads to cell death within 7 days. The cells have been continuously maintained in this environment without morphological alteration or cessation of growth for more than 5 months. Addition of the anti-estrogen, Tamoxifen (10(-6) M), inhibited cells below the growth rate seen when estradiol was omitted from the medium, even when Tamoxifen was added 4 days and two medium changes after the removal of estradiol from the medium, thus suggesting an action of Tamoxifen which may be independent of competition with estradiol. The availability of a human breast cancer cell line that can be propagated in hormone-supplemented medium without serum should aid in the study of the mechanisms by which hormones effect cell growth."}
{"id": "PMID:212181", "title": "A new in vitro cell line established from human large cell variant of oat cell lung cancer.", "content": "A new tissue culture cell line, SHP-77, has been established from explant cultures of a primary human lung cancer. Although the latter exhibited histological features of the so-called large or polygonal cell undifferentiated variant, neurosecretory granules were detected ultrastructurally in cells of the original tumor, culture line, and neoplasms developing after transplantation of the latter in nude mice. These features attest to the identity of the original tumor as a large-cell variant of oat cell cancer. In addition, electron microscopy revealed the presence of gland formation and intracytoplasmic lamellar bodies in the cells of SHP-77. This information indicates the potential for varied differentiation and morphological expression of so-called undifferentiated lung cancer cells and is pertinent to nosological considerations concerning human lung cancer. The cell line has maintained its morphological, karyotypic, chromosomal, and growth characteristics after transplantation to nude mice. Because of this stability, SHP-77 appears to represent a propitious cell line for in vitro and in vivo biological and therapeutic studies of this type of lung cancer.", "contents": "A new in vitro cell line established from human large cell variant of oat cell lung cancer. A new tissue culture cell line, SHP-77, has been established from explant cultures of a primary human lung cancer. Although the latter exhibited histological features of the so-called large or polygonal cell undifferentiated variant, neurosecretory granules were detected ultrastructurally in cells of the original tumor, culture line, and neoplasms developing after transplantation of the latter in nude mice. These features attest to the identity of the original tumor as a large-cell variant of oat cell cancer. In addition, electron microscopy revealed the presence of gland formation and intracytoplasmic lamellar bodies in the cells of SHP-77. This information indicates the potential for varied differentiation and morphological expression of so-called undifferentiated lung cancer cells and is pertinent to nosological considerations concerning human lung cancer. The cell line has maintained its morphological, karyotypic, chromosomal, and growth characteristics after transplantation to nude mice. Because of this stability, SHP-77 appears to represent a propitious cell line for in vitro and in vivo biological and therapeutic studies of this type of lung cancer."}
{"id": "PMID:212183", "title": "A differential interaction of daunomycin, adriamycin, and N-trifluoroacetyladriamycin 14-valerate with mouse peritoneal macrophages.", "content": "The interaction of three anthracycline drugs, daunomycin, Adriamycin, and N-trifluoroacetyladriamycin 14-valerate, with mouse peritoneal macrophages was explored. As assessed by drug-specific cytofluorescence, Adriamycin and daunomycin accumulated slowly within macrophages, first staining the nucleus and then the cytoplasmic inclusions that were induced by the drug treatment. N-Trifluoroacetyladriamycin 14-valerate distributed rapidly into the cells, was excluded from the nucleus, and induced numerous cytoplasmic inclusions. Electron microscopy revealed that the cytoplasmic inclusions were vacuoles containing some amorphous material and not the classical autophagic vacuoles containing organelles and membrane lamellae. All the drugs induced cell shrinkage with time and brought about cell death within 24 hr. Loss of cell function and viability was dose and time dependent; i.e., a 6-hr incubation with daunomycin or Adriamycin, 2.5 microgram/ml, brought about a 50% reduction in the phagocytic capacity of the treated macrophages. The damaging potency towards macrophages (daunomycin greater than Adriamycin greater than N-trifluoroacetyladriamycin 14-valerate) is in the reverse order to the in vivo therapeutic efficiency.", "contents": "A differential interaction of daunomycin, adriamycin, and N-trifluoroacetyladriamycin 14-valerate with mouse peritoneal macrophages. The interaction of three anthracycline drugs, daunomycin, Adriamycin, and N-trifluoroacetyladriamycin 14-valerate, with mouse peritoneal macrophages was explored. As assessed by drug-specific cytofluorescence, Adriamycin and daunomycin accumulated slowly within macrophages, first staining the nucleus and then the cytoplasmic inclusions that were induced by the drug treatment. N-Trifluoroacetyladriamycin 14-valerate distributed rapidly into the cells, was excluded from the nucleus, and induced numerous cytoplasmic inclusions. Electron microscopy revealed that the cytoplasmic inclusions were vacuoles containing some amorphous material and not the classical autophagic vacuoles containing organelles and membrane lamellae. All the drugs induced cell shrinkage with time and brought about cell death within 24 hr. Loss of cell function and viability was dose and time dependent; i.e., a 6-hr incubation with daunomycin or Adriamycin, 2.5 microgram/ml, brought about a 50% reduction in the phagocytic capacity of the treated macrophages. The damaging potency towards macrophages (daunomycin greater than Adriamycin greater than N-trifluoroacetyladriamycin 14-valerate) is in the reverse order to the in vivo therapeutic efficiency."}
{"id": "PMID:212184", "title": "5-Methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid (folinic acid), and folic acid requirements of normal and Rous sarcoma virus-infected chicken fibroblasts.", "content": "Normal and Rous sarcoma virus-infected chicken fibroblasts proliferate maximally in a culture medium containing a physiological (10 ng/ml) concentration of 5-methyltetrahydrofolic acid or folinic acid (5-formyltetrahydrofolic acid), while their maximal proliferation requires a hyperphysiological (1000 ng/ml) concentration of folic acid. The normal and Rous-infected fibroblasts do not differ in their requirements for 5-methyltetrahydrofolate, folinic acid, or folic acid.", "contents": "5-Methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid (folinic acid), and folic acid requirements of normal and Rous sarcoma virus-infected chicken fibroblasts. Normal and Rous sarcoma virus-infected chicken fibroblasts proliferate maximally in a culture medium containing a physiological (10 ng/ml) concentration of 5-methyltetrahydrofolic acid or folinic acid (5-formyltetrahydrofolic acid), while their maximal proliferation requires a hyperphysiological (1000 ng/ml) concentration of folic acid. The normal and Rous-infected fibroblasts do not differ in their requirements for 5-methyltetrahydrofolate, folinic acid, or folic acid."}
{"id": "PMID:212185", "title": "Role of exogenous female hormones in altering the risk of benign and malignant neoplasms in humans.", "content": "The epidemiological and clinical evidence for various forms of exogenous estrogens altering the risk of neoplasms of the female genital system, breast, and liver are reviewed and evaluated. It is virtually certain that in utero exposure to diethylstilbestrol can cause clear cell adenocarcinomas of the vagina and cervix. There is strong evidence that various estrogens given for treatment of menopausal symptoms can cause endometrial carcinoma and that sequential oral contraceptives probably also do so. Oral contraceptives very probably reduce the risk of both cystic disease and fibroadenoma of the breast and increase the risk of liver cell adenomas. Studies to date do not provide consistent and convincing evidence that any form of exogenous estrogen alters the risk of cancers of the breast or ovary or that oral contraceptives alter the risk of cervical neoplasia or focal nodular hyperplasia of the liver, although recent reports suggest that continued vigilance is warranted. Specific topics requiring further epidemiological investigation are suggested.", "contents": "Role of exogenous female hormones in altering the risk of benign and malignant neoplasms in humans. The epidemiological and clinical evidence for various forms of exogenous estrogens altering the risk of neoplasms of the female genital system, breast, and liver are reviewed and evaluated. It is virtually certain that in utero exposure to diethylstilbestrol can cause clear cell adenocarcinomas of the vagina and cervix. There is strong evidence that various estrogens given for treatment of menopausal symptoms can cause endometrial carcinoma and that sequential oral contraceptives probably also do so. Oral contraceptives very probably reduce the risk of both cystic disease and fibroadenoma of the breast and increase the risk of liver cell adenomas. Studies to date do not provide consistent and convincing evidence that any form of exogenous estrogen alters the risk of cancers of the breast or ovary or that oral contraceptives alter the risk of cervical neoplasia or focal nodular hyperplasia of the liver, although recent reports suggest that continued vigilance is warranted. Specific topics requiring further epidemiological investigation are suggested."}
{"id": "PMID:212187", "title": "Hormonal induction of mammary tumor viruses and its implications for carcinogenesis.", "content": "The purpose of this study was to evaluate the possibility that hormones and mouse mammary tumor virus (MuMTV) are cocarcinogenic for mammary epithelium. Results of our investigations in vivo and in vitro suggest: (a) Hormones promote mammary carcinogenesis in BALB/c females whether MuMTV is germinally (BALB/c) or horizontally (BALB/cfC3H) transmitted; the rate of carcinogenesis in BALB/cfC3H females is substantially faster than it is in BALB/c, but the final mammary carcinoma incidence is approximately the same. The rate-limiting step in malignant transformation in BALB/c, which infectious MuMTV overcomes, is in premalignant transformation from normal. (b) One characteristic of horizontal MuMTV transmission in BALB/c that is not observed in germinal transmission is integration of new MuMTV sequences in mammary cell DNA. Integration is mammary cell specific and constant at 2 to 3 copies/cell from tumor to tumor. (c) MuMTV expression is changed in mammary epithelial cells during hormonal carcinogenesis. The nature of the change is qualitatively similar in both BALB/c and BALB/cfC3H. Expression of envelope glycopeptides (glycoprotein with a molecular weight of 52,000) is induced, which correlates with amplification of MuMTV RNA sequence content. Quantitative differences exist in induced levels in BALB/c and BALB/cfC3H. (d) MuMTV RNA and a glycoprotein with a molecular weight of 52,000 were not inducible with dexamethasone in normal mammary epithelial cells in culture. These structural components were induced in both premalignant (BALB/cfC3H) and malignant (BALB/c and BALB/cfC3H) cells. MuMTV RNA was induced by dexamethasone in normal cells pretreated with 5-iodo-2'-deoxyuridine. (e) Both premalignant and malignant cells have altered (vis-\u00e0-vis normal) surfaces, discernible by differences in reactivity with concanavalin A in hemadsorption assays. Indirect evidence suggests that the alteration includes membrane incorporation of MuMTV-related determinants of a glycoprotein with a molecular weight of 52,000. (f) Malignant cells exhibit enhanced sensitivity to insulin for reinitiation of DNA synthesis and mitosis in contact-inhibited homotypical monolayers. These findings have been organized into a hormonal cocarcinogenesis hypothesis in which expression of germinally transmitted MuMTV genes is the proximal cause of neoplastic transformation.", "contents": "Hormonal induction of mammary tumor viruses and its implications for carcinogenesis. The purpose of this study was to evaluate the possibility that hormones and mouse mammary tumor virus (MuMTV) are cocarcinogenic for mammary epithelium. Results of our investigations in vivo and in vitro suggest: (a) Hormones promote mammary carcinogenesis in BALB/c females whether MuMTV is germinally (BALB/c) or horizontally (BALB/cfC3H) transmitted; the rate of carcinogenesis in BALB/cfC3H females is substantially faster than it is in BALB/c, but the final mammary carcinoma incidence is approximately the same. The rate-limiting step in malignant transformation in BALB/c, which infectious MuMTV overcomes, is in premalignant transformation from normal. (b) One characteristic of horizontal MuMTV transmission in BALB/c that is not observed in germinal transmission is integration of new MuMTV sequences in mammary cell DNA. Integration is mammary cell specific and constant at 2 to 3 copies/cell from tumor to tumor. (c) MuMTV expression is changed in mammary epithelial cells during hormonal carcinogenesis. The nature of the change is qualitatively similar in both BALB/c and BALB/cfC3H. Expression of envelope glycopeptides (glycoprotein with a molecular weight of 52,000) is induced, which correlates with amplification of MuMTV RNA sequence content. Quantitative differences exist in induced levels in BALB/c and BALB/cfC3H. (d) MuMTV RNA and a glycoprotein with a molecular weight of 52,000 were not inducible with dexamethasone in normal mammary epithelial cells in culture. These structural components were induced in both premalignant (BALB/cfC3H) and malignant (BALB/c and BALB/cfC3H) cells. MuMTV RNA was induced by dexamethasone in normal cells pretreated with 5-iodo-2'-deoxyuridine. (e) Both premalignant and malignant cells have altered (vis-\u00e0-vis normal) surfaces, discernible by differences in reactivity with concanavalin A in hemadsorption assays. Indirect evidence suggests that the alteration includes membrane incorporation of MuMTV-related determinants of a glycoprotein with a molecular weight of 52,000. (f) Malignant cells exhibit enhanced sensitivity to insulin for reinitiation of DNA synthesis and mitosis in contact-inhibited homotypical monolayers. These findings have been organized into a hormonal cocarcinogenesis hypothesis in which expression of germinally transmitted MuMTV genes is the proximal cause of neoplastic transformation."}
{"id": "PMID:212189", "title": "Relationships of the structure and function of the interferon receptor to hormone receptors and establishment of the antiviral state.", "content": "This report describes similarities between the structure and function of the interferon receptor and receptors for glycoprotein hormones and several bacterial toxins. Specifically, it describes several common molecular and mechanistic elements, including: (a) the presence of a glycoprotein as well as a ganglioside component in the receptor; (b) changes in membrane structure as a consequence of interferon action; (c) interferon-induced intracellular cyclic adenosine 3':5'-monophosphate changes; and (d) alterations in the flux of certain ions across the membrane. Since interferon has an antiviral effect, these results define a relationship between hormonal perturbation of cellular events and the ability of an agent to prevent or suppress viral infections of cells. Further definition of these relationships should be important to our understanding of the oncogenic state, of hormonal effects on the oncogenic state, and of other human diseases in which hormonal perturbations of non-target tissues or cross-reactivity of receptors could be pathogenic.", "contents": "Relationships of the structure and function of the interferon receptor to hormone receptors and establishment of the antiviral state. This report describes similarities between the structure and function of the interferon receptor and receptors for glycoprotein hormones and several bacterial toxins. Specifically, it describes several common molecular and mechanistic elements, including: (a) the presence of a glycoprotein as well as a ganglioside component in the receptor; (b) changes in membrane structure as a consequence of interferon action; (c) interferon-induced intracellular cyclic adenosine 3':5'-monophosphate changes; and (d) alterations in the flux of certain ions across the membrane. Since interferon has an antiviral effect, these results define a relationship between hormonal perturbation of cellular events and the ability of an agent to prevent or suppress viral infections of cells. Further definition of these relationships should be important to our understanding of the oncogenic state, of hormonal effects on the oncogenic state, and of other human diseases in which hormonal perturbations of non-target tissues or cross-reactivity of receptors could be pathogenic."}
{"id": "PMID:212190", "title": "Investigation of hormone-receptor interactions by means of fluorescence labeling.", "content": "Fluorescent-labeled hormones can be used to study hormone-receptor interactions by means of fluorescence polarization, visualization by fluorescence microscopy, or separation methods, e.g., dextran-coated charcoal. Subcellular fragments, single cells, and tissue preparations are amenable to study; in this work rat uterine cytosol was used unless otherwise noted. Estrone labeled with fluorescein at position 17 gives 50% inhibition in the radiometric dextran-coated charcoal assay at 8.3 X 10(-7) M as compared to 3.4 and 3.5 X 10(-8) M for diethylstilbestrol and estradiol, respectively. Scatchard plots from fluorescence polarization are hyperbolic and consistent with two classes of binding sites having association constants 5.6 X 10(10) and 6.4 X 10(7) M-1. Binding by high-affinity sites, which were present at about 3 times the concentraion of \"specific\" sites (radiometric dextran-coated charcoal assay), was abrogated by estradiol or diethylstilbestrol. Kinetic measurements showed that binding sites that can be blocked by excess estradiol or diethylstilbestrol are those that are both slowly associating and slowly dissociating. Staining of tissues by estrone labeled with fluorescein at position 17 as seen in the fluorescence microscope showed specificity. In normal rat uterus only epithelial cells were stained. In one human infiltrating ductal carcinoma only the malignant ductoid elements stained, while in another there was essentially no staining.", "contents": "Investigation of hormone-receptor interactions by means of fluorescence labeling. Fluorescent-labeled hormones can be used to study hormone-receptor interactions by means of fluorescence polarization, visualization by fluorescence microscopy, or separation methods, e.g., dextran-coated charcoal. Subcellular fragments, single cells, and tissue preparations are amenable to study; in this work rat uterine cytosol was used unless otherwise noted. Estrone labeled with fluorescein at position 17 gives 50% inhibition in the radiometric dextran-coated charcoal assay at 8.3 X 10(-7) M as compared to 3.4 and 3.5 X 10(-8) M for diethylstilbestrol and estradiol, respectively. Scatchard plots from fluorescence polarization are hyperbolic and consistent with two classes of binding sites having association constants 5.6 X 10(10) and 6.4 X 10(7) M-1. Binding by high-affinity sites, which were present at about 3 times the concentraion of \"specific\" sites (radiometric dextran-coated charcoal assay), was abrogated by estradiol or diethylstilbestrol. Kinetic measurements showed that binding sites that can be blocked by excess estradiol or diethylstilbestrol are those that are both slowly associating and slowly dissociating. Staining of tissues by estrone labeled with fluorescein at position 17 as seen in the fluorescence microscope showed specificity. In normal rat uterus only epithelial cells were stained. In one human infiltrating ductal carcinoma only the malignant ductoid elements stained, while in another there was essentially no staining."}
{"id": "PMID:212191", "title": "Regulation of S49 lymphoma cell growth by cyclic adenosine 3':5'-monophosphate.", "content": "S49 lymphoma tissue culture cells arrest in the G1 phase of the cell cycle when treated with agents that elevate endogenous cyclic adenosine 3':5'-monophosphate (cAMP), such as cholera toxin or exogenously added active congeners of cAMP such as N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP). This phenomenon requires that cells contain the appropriate receptors: Mutant cells deficient in adenylyl cyclase fail to arrest in response to cholera toxin, and another mutant that lacks cAMP-dependent protein kinase does not respond to cholera toxin or to Bt2cAMP. The size distribution of cell populations treated with Bt2cAMP changes in a manner that reflects only the perturbation of cell cycle distribution. Arrested G1 cells in particular have the same volume as the G1 cells of an exponentially growing population. When G1 cells that have been arrested by Bt2cAMP are grown in fresh medium free of Bt2cAMP, they begin to reenter S phase after a delay of about 6 hr and do so with pseudo-first-order kinetics, with a half-life of 5 hr. These and other properties previously described suggest that cAMP regulates S49 cell growth by physiologically significant rather than artifactual mechanisms.", "contents": "Regulation of S49 lymphoma cell growth by cyclic adenosine 3':5'-monophosphate. S49 lymphoma tissue culture cells arrest in the G1 phase of the cell cycle when treated with agents that elevate endogenous cyclic adenosine 3':5'-monophosphate (cAMP), such as cholera toxin or exogenously added active congeners of cAMP such as N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP). This phenomenon requires that cells contain the appropriate receptors: Mutant cells deficient in adenylyl cyclase fail to arrest in response to cholera toxin, and another mutant that lacks cAMP-dependent protein kinase does not respond to cholera toxin or to Bt2cAMP. The size distribution of cell populations treated with Bt2cAMP changes in a manner that reflects only the perturbation of cell cycle distribution. Arrested G1 cells in particular have the same volume as the G1 cells of an exponentially growing population. When G1 cells that have been arrested by Bt2cAMP are grown in fresh medium free of Bt2cAMP, they begin to reenter S phase after a delay of about 6 hr and do so with pseudo-first-order kinetics, with a half-life of 5 hr. These and other properties previously described suggest that cAMP regulates S49 cell growth by physiologically significant rather than artifactual mechanisms."}
{"id": "PMID:212192", "title": "Role of pituitary hormones in the growth of human breast cancer.", "content": "Hypophysectomy was performed in 28 women with Stage IV breast cancer who were treated initially with antiestrogens. Six of 13 patients who responded to tamoxifen and 2 of 12 who failed to benefit from tamoxifen obtained remissions from hypophysectomy. The remissions average 11+ months. Three of 8 patients treated initially with antiestrogens have responded to androgen therapy. The results suggest that hormones other than estrogen, which appears to play a major role, may be involved in stimulating the growth of some human breast cancers. Prolactin receptors were detectable in 51% of human breast cancers and were detected in both estrogen receptor-positive and -negative tumors. Preliminary clinical correlations suggest that prolactin receptors will not be useful in predicting response to antiestrogen therapy.", "contents": "Role of pituitary hormones in the growth of human breast cancer. Hypophysectomy was performed in 28 women with Stage IV breast cancer who were treated initially with antiestrogens. Six of 13 patients who responded to tamoxifen and 2 of 12 who failed to benefit from tamoxifen obtained remissions from hypophysectomy. The remissions average 11+ months. Three of 8 patients treated initially with antiestrogens have responded to androgen therapy. The results suggest that hormones other than estrogen, which appears to play a major role, may be involved in stimulating the growth of some human breast cancers. Prolactin receptors were detectable in 51% of human breast cancers and were detected in both estrogen receptor-positive and -negative tumors. Preliminary clinical correlations suggest that prolactin receptors will not be useful in predicting response to antiestrogen therapy."}
{"id": "PMID:212193", "title": "Human breast carcinoma cells in continuous culture: a review.", "content": "A comprehensive listing of putative human breast carcinoma cell lines and the extent to which each has been characterized is presented. Criteria used to certify the human, mammary, and malignant origin of a cell line include: (a) a reliable histopathological diagnosis; (b) interspecies specificity established by human karyotype, isoenzyme profiles, and/or cell surface antigenicity; (c) intraspecies specificity, demonstrated by genetic evidence of a unique, human donor distinct from other cells including HeLa cells; and (d) organ specficity, supported by morphological evidence of epithelial structure and secretory activity, and especially by the expression of differentiated functions; these include presence of receptors for sex steroid hormones, hormone responsiveness, and production of milk proteins, fatty acids, or milk-specific antigens. Of the 47 cell lines for which data are here reported, 22 have been shown to be derived from human non-HeLa donors and to have epithelial morphology as revealed by light or electron microscopy. Differentiated function has been recorded for 19 cell lines. Additional human breast cancer cell lines have been reported, but characterization of some of these has been insufficient to judge the legitimacy of their predigrees. For others mammary origin is questionable. Six purported breast cell lines are in reality HeLa cells, and one is of nonhuman origin.", "contents": "Human breast carcinoma cells in continuous culture: a review. A comprehensive listing of putative human breast carcinoma cell lines and the extent to which each has been characterized is presented. Criteria used to certify the human, mammary, and malignant origin of a cell line include: (a) a reliable histopathological diagnosis; (b) interspecies specificity established by human karyotype, isoenzyme profiles, and/or cell surface antigenicity; (c) intraspecies specificity, demonstrated by genetic evidence of a unique, human donor distinct from other cells including HeLa cells; and (d) organ specficity, supported by morphological evidence of epithelial structure and secretory activity, and especially by the expression of differentiated functions; these include presence of receptors for sex steroid hormones, hormone responsiveness, and production of milk proteins, fatty acids, or milk-specific antigens. Of the 47 cell lines for which data are here reported, 22 have been shown to be derived from human non-HeLa donors and to have epithelial morphology as revealed by light or electron microscopy. Differentiated function has been recorded for 19 cell lines. Additional human breast cancer cell lines have been reported, but characterization of some of these has been insufficient to judge the legitimacy of their predigrees. For others mammary origin is questionable. Six purported breast cell lines are in reality HeLa cells, and one is of nonhuman origin."}
{"id": "PMID:212195", "title": "Inhibition of spermiation in the Syrian hamster using dibutyryl cyclic-AMP.", "content": "Young adult male Syrian hamsters were given intraperitoneal injections of 50 mg dibutyryl cyclic AMP twice daily for a period of three days. On the fourth day the animals were sacrificed and their testes were processed for light and electron microscopy. The results indicate that the mature spermatozoa were retained within the seminiferous epithelium after the stage in the seminiferous cycle in which spermiation normally occurs. The unreleased spermatozoa were ultrastructurally normal. Typical Sertoli-spermatid junctional specializations remained associated with the retained spermatozoa. These findings indicate that normally spermiation is initiated by the disappearance of the junctional specializations. In addition, the present results demonstrate that spermiation can be controlled.", "contents": "Inhibition of spermiation in the Syrian hamster using dibutyryl cyclic-AMP. Young adult male Syrian hamsters were given intraperitoneal injections of 50 mg dibutyryl cyclic AMP twice daily for a period of three days. On the fourth day the animals were sacrificed and their testes were processed for light and electron microscopy. The results indicate that the mature spermatozoa were retained within the seminiferous epithelium after the stage in the seminiferous cycle in which spermiation normally occurs. The unreleased spermatozoa were ultrastructurally normal. Typical Sertoli-spermatid junctional specializations remained associated with the retained spermatozoa. These findings indicate that normally spermiation is initiated by the disappearance of the junctional specializations. In addition, the present results demonstrate that spermiation can be controlled."}
{"id": "PMID:212196", "title": "Structure of the Adenohypophysis in parturient female and neonate harp seals, Pagophilus groenlandicus.", "content": "The pars distalis of parturient harp seals (Pagophilus groenlandicus) is divisible into three distinct zones based on the major cellular components of the different regions. A clear zonation is lacking in neonate seals, the medical \"basophilic wedge\" and the anterior gonadotrophic were small and difficult to identify. Five cell types were identified based on cytological characteristics: somatotrophs, mammotrophs, thyrotrophs, gonadotrophs and stellate cells; corticotrophs could not be identified, with any certainty, in any of the preparations, nor could the gonadotrophs be classified into LH, FSH, and ICSH cells. The pars intermedia enlarged during the early post-partum period and was large in the parturient females.", "contents": "Structure of the Adenohypophysis in parturient female and neonate harp seals, Pagophilus groenlandicus. The pars distalis of parturient harp seals (Pagophilus groenlandicus) is divisible into three distinct zones based on the major cellular components of the different regions. A clear zonation is lacking in neonate seals, the medical \"basophilic wedge\" and the anterior gonadotrophic were small and difficult to identify. Five cell types were identified based on cytological characteristics: somatotrophs, mammotrophs, thyrotrophs, gonadotrophs and stellate cells; corticotrophs could not be identified, with any certainty, in any of the preparations, nor could the gonadotrophs be classified into LH, FSH, and ICSH cells. The pars intermedia enlarged during the early post-partum period and was large in the parturient females."}
{"id": "PMID:212197", "title": "The complete sequence of a unique RNA species synthesized by a DI particle of VSV.", "content": "The 2S RNA synthesized in vitro by the RNA polymerase of a defective interfering (DI) particle of vesicular stomatitis virus was labeled at its 3' terminus with 32P-cytidine 3', 5' bisphosphate and RNA ligase. Analysis of the labeled RNA showed that it was a family of RNAs of different length but all sharing the same 5' terminal sequence. The largest labeled RNA was purified by gel electrophoresis, and the sequence of 41 of its 46 nucleotides was determined by rapid RNA sequencing methods. The assignment of the remaining 5 nucleotides was made on the basis of an analysis of one of the smaller RNAs and published data. A new approach in RNA sequencing based on the identification of 3' terminal nucleotides of rna fragments originally present in the DI product or generated during the ligation reaction confirmed most of the sequence. The complete sequence of this 46 nucleotide long plus-sense RNA is: ppACGAAGACCACAAAACCAGAUAAAAAA UAAAAACCACAAGAGGGUC-OH. This RNA anneals to the RNA of the DI particle from which it was synthesized, indicating that its synthesis is template-specified. At least the first 17 and possibly all of the nucleotides are also complementary to sequences at the 3' end of two other VSV DI particles which were derived independently and whose genomes differ significantly in length. These data suggest a common 3' terminal sequence among all VSV DI particles which contain part of the Lgene region of the parental genome.", "contents": "The complete sequence of a unique RNA species synthesized by a DI particle of VSV. The 2S RNA synthesized in vitro by the RNA polymerase of a defective interfering (DI) particle of vesicular stomatitis virus was labeled at its 3' terminus with 32P-cytidine 3', 5' bisphosphate and RNA ligase. Analysis of the labeled RNA showed that it was a family of RNAs of different length but all sharing the same 5' terminal sequence. The largest labeled RNA was purified by gel electrophoresis, and the sequence of 41 of its 46 nucleotides was determined by rapid RNA sequencing methods. The assignment of the remaining 5 nucleotides was made on the basis of an analysis of one of the smaller RNAs and published data. A new approach in RNA sequencing based on the identification of 3' terminal nucleotides of rna fragments originally present in the DI product or generated during the ligation reaction confirmed most of the sequence. The complete sequence of this 46 nucleotide long plus-sense RNA is: ppACGAAGACCACAAAACCAGAUAAAAAA UAAAAACCACAAGAGGGUC-OH. This RNA anneals to the RNA of the DI particle from which it was synthesized, indicating that its synthesis is template-specified. At least the first 17 and possibly all of the nucleotides are also complementary to sequences at the 3' end of two other VSV DI particles which were derived independently and whose genomes differ significantly in length. These data suggest a common 3' terminal sequence among all VSV DI particles which contain part of the Lgene region of the parental genome."}
{"id": "PMID:212199", "title": "Characterization of T antigens in polyoma-infected and transformed cells.", "content": "Polyoma-infected 3T6 cells contain a number of proteins precipitable by serum from rats carrying polyoma-induced tumors. The virus codes for three species having apparent molecular weights of 90,000, 60,000 and 22,000 daltons, as determined by polyacrylamide gel electrophoresis (90K, 60K and 22k). The 90K and 22K species produced by a large plaque and a small plaque wild-type polyoma have similar mobilities, but the 60K species produced by the large plaque wild-type. In cells infected by each of seven polyoma tsA mutants, the 90K species is unstable at the nonpermissive temperature, while the 60K and 22K species are stable. In cells infected by a mutant carrying a deletion between roughly 98 and 3 map units in the early region of the viral genome, the 22K species is present, but the 90K and 60K species are absent. Tryptic peptide analysis of the isolated 90K, 60K and 22K species shows that the three species have common N terminal regions. The 60K and 22K species contain amino acid sequences not found in the 90K species , and the 60K species has several unique, methionine-containing peptides not found in either the 22K or 90K species. Two polyoma-transformed BHK cell lines do not have detectable amounts of the 90K protein.", "contents": "Characterization of T antigens in polyoma-infected and transformed cells. Polyoma-infected 3T6 cells contain a number of proteins precipitable by serum from rats carrying polyoma-induced tumors. The virus codes for three species having apparent molecular weights of 90,000, 60,000 and 22,000 daltons, as determined by polyacrylamide gel electrophoresis (90K, 60K and 22k). The 90K and 22K species produced by a large plaque and a small plaque wild-type polyoma have similar mobilities, but the 60K species produced by the large plaque wild-type. In cells infected by each of seven polyoma tsA mutants, the 90K species is unstable at the nonpermissive temperature, while the 60K and 22K species are stable. In cells infected by a mutant carrying a deletion between roughly 98 and 3 map units in the early region of the viral genome, the 22K species is present, but the 90K and 60K species are absent. Tryptic peptide analysis of the isolated 90K, 60K and 22K species shows that the three species have common N terminal regions. The 60K and 22K species contain amino acid sequences not found in the 90K species , and the 60K species has several unique, methionine-containing peptides not found in either the 22K or 90K species. Two polyoma-transformed BHK cell lines do not have detectable amounts of the 90K protein."}
{"id": "PMID:212200", "title": "At least 104 nucleotides are transposed from the 5' terminus of the avian sarcoma virus genome to the 5' termini of smaller viral mRNAs.", "content": "Cells producing avian sarcoma virus (ASV) contain at least three virus-specific mRNAs, two of which are encoded within the 3' half of the viral genome. Each of these viral RNAs can hybridize with single-stranded DNA(cDNA5') that is complementary to a sequence of 101 nucleotides found at the 5' terminus of the ASV genome, but not within the 3' half of the genome. We proposed previously (Weiss, Varmus and Bishop, 1977) that this nucleotide sequence may be transposed to the 5' termini of viral mRNAs during the genesis of these RNAs. We now substantiate this proposal by reporting the isolation and chemical characterization of the nucleotide sequences complementary to cDNA5' in the genome and mRNAs of the Prague B strain of ASV. We isolated the three identified classes of ASVmRNA (38, 28 and 21S) by molecular hybridization; each class of RNA contained a \"capped\" oligonucleotide identical to that found at the 5' terminus of the ASV genome. When hybridized with cDNA5', each class of RNA gave rise to RNAase-resistant duplex hybrids that probably encompassed the full extent of cDNA5'. The molar yields of duplex conformed approximately to the number of virus-specific RNA molecules in the initial samples; hence most if not all of the molecules of virus-specific RNA could give rise to the duplexes. The duplexes prepared from the various RNAs all contained the capped oligonucleotide found at the 5' terminus of the viral genome and had identical \"fingerprints\" when analyzed by two-dimensional fractionation following hydrolysis with RNAase T1. In contrast, RNA representing the 3' half of the ASV genome did not form hybrids with cDNA5'. We conclude that a sequence of more than 100 nucleotides is transposed from the 5' end of the ASV genome to the 5' termini of smaller viral RNAs during the genesis of these RNAs. Transposition of nucleotide sequences during the production of mRNA has now been described for three families of animal viruses and may be a common feature of mRNA biogenesis in eucaryotic cells. The mechanism of transposition, however, and the function of the transposed sequences are not known.", "contents": "At least 104 nucleotides are transposed from the 5' terminus of the avian sarcoma virus genome to the 5' termini of smaller viral mRNAs. Cells producing avian sarcoma virus (ASV) contain at least three virus-specific mRNAs, two of which are encoded within the 3' half of the viral genome. Each of these viral RNAs can hybridize with single-stranded DNA(cDNA5') that is complementary to a sequence of 101 nucleotides found at the 5' terminus of the ASV genome, but not within the 3' half of the genome. We proposed previously (Weiss, Varmus and Bishop, 1977) that this nucleotide sequence may be transposed to the 5' termini of viral mRNAs during the genesis of these RNAs. We now substantiate this proposal by reporting the isolation and chemical characterization of the nucleotide sequences complementary to cDNA5' in the genome and mRNAs of the Prague B strain of ASV. We isolated the three identified classes of ASVmRNA (38, 28 and 21S) by molecular hybridization; each class of RNA contained a \"capped\" oligonucleotide identical to that found at the 5' terminus of the ASV genome. When hybridized with cDNA5', each class of RNA gave rise to RNAase-resistant duplex hybrids that probably encompassed the full extent of cDNA5'. The molar yields of duplex conformed approximately to the number of virus-specific RNA molecules in the initial samples; hence most if not all of the molecules of virus-specific RNA could give rise to the duplexes. The duplexes prepared from the various RNAs all contained the capped oligonucleotide found at the 5' terminus of the viral genome and had identical \"fingerprints\" when analyzed by two-dimensional fractionation following hydrolysis with RNAase T1. In contrast, RNA representing the 3' half of the ASV genome did not form hybrids with cDNA5'. We conclude that a sequence of more than 100 nucleotides is transposed from the 5' end of the ASV genome to the 5' termini of smaller viral RNAs during the genesis of these RNAs. Transposition of nucleotide sequences during the production of mRNA has now been described for three families of animal viruses and may be a common feature of mRNA biogenesis in eucaryotic cells. The mechanism of transposition, however, and the function of the transposed sequences are not known."}
{"id": "PMID:212201", "title": "Complete nucleotide sequence of the leader RNA synthesized in vitro by vesicular stomatitis virus.", "content": "The complete nucleotide sequence of the leader RNA synthesized in vitro by the Indiana serotype of vesicular stomatitis virus is presented. The sequence was determined by the technique described by Donis-Keller, Maxam and Gilbert (1977) in combination with the standard two-dimensional fingerprint techniques described by Barrell (1971). The leader RNA contains 48 nucleotides variably terminating at the 3' terminus with cytosine (68%) and adenosine at position 47 (32%). Since the leader RNA is complementary to the 3' terminal portion of the viral genome RNA, the first 48 nucleotides from the 3' end of the genome RNA can be decuded. The leader RNA contains repetitive and palindromic sequences with a polypurine sequence at its 3' terminus. The possible role of some of the sequences is discussed.", "contents": "Complete nucleotide sequence of the leader RNA synthesized in vitro by vesicular stomatitis virus. The complete nucleotide sequence of the leader RNA synthesized in vitro by the Indiana serotype of vesicular stomatitis virus is presented. The sequence was determined by the technique described by Donis-Keller, Maxam and Gilbert (1977) in combination with the standard two-dimensional fingerprint techniques described by Barrell (1971). The leader RNA contains 48 nucleotides variably terminating at the 3' terminus with cytosine (68%) and adenosine at position 47 (32%). Since the leader RNA is complementary to the 3' terminal portion of the viral genome RNA, the first 48 nucleotides from the 3' end of the genome RNA can be decuded. The leader RNA contains repetitive and palindromic sequences with a polypurine sequence at its 3' terminus. The possible role of some of the sequences is discussed."}
{"id": "PMID:212202", "title": "Dexamethasone-mediated induction of mouse mammary tumor virus RNA: a system for studying glucocorticoid action.", "content": "We have investigated the mechanisms by which dexamethasone (a synthetic glucocorticoid) stimulates the production of mouse mammary tumor virus (MMTV) by cell cultures derived from mammary carcinomas of GR mice. Treatment of these cells with dexamethasone stimulates a rapid accumulation of intracellular virus-specific RNA which is dependent upon RNA synthesis but not upon DNA or protein synthesis. The effect of dexamethasone is probably mediated by a specific and saturable glucocorticoid receptor. We conclude that the accumulation of MMTV RNA is a primary response to dexamethasone and that the rate of synthesis of MMTV RNA is probably accelerated by treatment with dexamethasone.", "contents": "Dexamethasone-mediated induction of mouse mammary tumor virus RNA: a system for studying glucocorticoid action. We have investigated the mechanisms by which dexamethasone (a synthetic glucocorticoid) stimulates the production of mouse mammary tumor virus (MMTV) by cell cultures derived from mammary carcinomas of GR mice. Treatment of these cells with dexamethasone stimulates a rapid accumulation of intracellular virus-specific RNA which is dependent upon RNA synthesis but not upon DNA or protein synthesis. The effect of dexamethasone is probably mediated by a specific and saturable glucocorticoid receptor. We conclude that the accumulation of MMTV RNA is a primary response to dexamethasone and that the rate of synthesis of MMTV RNA is probably accelerated by treatment with dexamethasone."}
{"id": "PMID:212203", "title": "Regulation of the activity of the low density lipoprotein receptor in human fibroblasts.", "content": "A specific receptor on the surface of cultured human fibroblasts binds plasma low density lipoprotein (LDL) with high affinity, and thereby initiates a cellular process by which the LDL is internalized and degraded within lysosomes and its cholesterol component is made available for cellular membrane synthesis. Current studies demonstrate that the activity of this LDL receptor is under feedback regulation. Prior incubation of fibroblast monolayers with cholesterol, 25-hydroxycholesterol, or LDL progressively reduced the ability of the cells to bind 125I-labeled LDL at the high affinity site. A series of kinetic studies indicated that this reduction in binding was due to a decrease in the number of LDL receptors. From measurements of the rate of decline in 125I-LDL binding activity after administration of cycloheximide, the LDL receptor was calculated to have a half-life of about 25 hr. LDL appeared to reduce 125I-LDL-binding activity by suppressing the synthesis of receptor molecules. Thus cultured human fibroblasts regulate their intracellular cholesterol content by regulating the activity of the LDL receptor, which in turn controls the rate of cellular entry of cholesterol derived from plasma LDL contained within the culture medium.", "contents": "Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. A specific receptor on the surface of cultured human fibroblasts binds plasma low density lipoprotein (LDL) with high affinity, and thereby initiates a cellular process by which the LDL is internalized and degraded within lysosomes and its cholesterol component is made available for cellular membrane synthesis. Current studies demonstrate that the activity of this LDL receptor is under feedback regulation. Prior incubation of fibroblast monolayers with cholesterol, 25-hydroxycholesterol, or LDL progressively reduced the ability of the cells to bind 125I-labeled LDL at the high affinity site. A series of kinetic studies indicated that this reduction in binding was due to a decrease in the number of LDL receptors. From measurements of the rate of decline in 125I-LDL binding activity after administration of cycloheximide, the LDL receptor was calculated to have a half-life of about 25 hr. LDL appeared to reduce 125I-LDL-binding activity by suppressing the synthesis of receptor molecules. Thus cultured human fibroblasts regulate their intracellular cholesterol content by regulating the activity of the LDL receptor, which in turn controls the rate of cellular entry of cholesterol derived from plasma LDL contained within the culture medium."}
{"id": "PMID:212204", "title": "Genetic determination of the alpha-galactosidase developmental program in mice.", "content": "The expression of alpha-galactosidase in liver, heart, and brain during postembryonic development has been examined in several inbred mouse strains. In most strains, the developmental patterns of alpha-galactosidase are coordinate with those of two other acid hydrolases, beta-glucuronidase and beta-galactosidase. Certain inbred mouse strains, including members of the C57-C58 family, have a tissue-specific alteration in the temporal expression of alpha-galactosidase activity. This alteration shows additive inheritance and appears to be controlled by a single genetic locus. The altered developmental expression of the enzyme is not accompanied by any discernible change in its physical properties.", "contents": "Genetic determination of the alpha-galactosidase developmental program in mice. The expression of alpha-galactosidase in liver, heart, and brain during postembryonic development has been examined in several inbred mouse strains. In most strains, the developmental patterns of alpha-galactosidase are coordinate with those of two other acid hydrolases, beta-glucuronidase and beta-galactosidase. Certain inbred mouse strains, including members of the C57-C58 family, have a tissue-specific alteration in the temporal expression of alpha-galactosidase activity. This alteration shows additive inheritance and appears to be controlled by a single genetic locus. The altered developmental expression of the enzyme is not accompanied by any discernible change in its physical properties."}
{"id": "PMID:212205", "title": "Ovarian plasminogen activator: relationship to ovulation and hormonal regulation.", "content": "A technique is described for detecting fibrinolytic activity of single cells in culture. This method was applied to the analysis of rat ovarian granulosa cells. Cells obtained from follicules shortly before ovulation show high levels of fibrinolytic activity. This activity is plasminogen-dependent, indicating that it is due to plasminogen activator. The appearance of this activity is correlated with ovulation by temporal and functional criteria, and can be demonstrated both in immature animals primed with hormones and in mature cycling animals. Granulosa cell cultures can be stimulated to release plasminogen activator by exposure in vitro either to luteinizing hormone or to dibutyryl cyclic AMP.", "contents": "Ovarian plasminogen activator: relationship to ovulation and hormonal regulation. A technique is described for detecting fibrinolytic activity of single cells in culture. This method was applied to the analysis of rat ovarian granulosa cells. Cells obtained from follicules shortly before ovulation show high levels of fibrinolytic activity. This activity is plasminogen-dependent, indicating that it is due to plasminogen activator. The appearance of this activity is correlated with ovulation by temporal and functional criteria, and can be demonstrated both in immature animals primed with hormones and in mature cycling animals. Granulosa cell cultures can be stimulated to release plasminogen activator by exposure in vitro either to luteinizing hormone or to dibutyryl cyclic AMP."}
{"id": "PMID:212206", "title": "Specific binding proteins for cyclic AMP and cyclic GMP in Dictyostelium discoideum.", "content": "In Dictyostelium discoideum both cyclic AMP and cyclic GMP are regulated by chemotactic stimuli. Binding proteins specific for cAMP and cGMP have been found in aggregation competent cells as well as in cells harvested during growth. The activity of binding proteins was, on the average, lower in the growth phase cells. cAMP binding proteins were separated into 3 fractions, whereas the cGMP binding activity appeared in 1 major peak both on DEAE-cellulose and Sephadex G-200. Protein kinase activity was present in most but not all cyclic necleotide binding fractions; evidence for a relationship is however missing.", "contents": "Specific binding proteins for cyclic AMP and cyclic GMP in Dictyostelium discoideum. In Dictyostelium discoideum both cyclic AMP and cyclic GMP are regulated by chemotactic stimuli. Binding proteins specific for cAMP and cGMP have been found in aggregation competent cells as well as in cells harvested during growth. The activity of binding proteins was, on the average, lower in the growth phase cells. cAMP binding proteins were separated into 3 fractions, whereas the cGMP binding activity appeared in 1 major peak both on DEAE-cellulose and Sephadex G-200. Protein kinase activity was present in most but not all cyclic necleotide binding fractions; evidence for a relationship is however missing."}
{"id": "PMID:212212", "title": "[An unusual case of polydactylia].", "content": "A woman of 85 had a symetrical malformation of the hands manifested as a combination of syndactyly of the soft parts of the 3rd and 4th fingers and an incomplete bifurcation of the bones of the 4th finger.", "contents": "[An unusual case of polydactylia]. A woman of 85 had a symetrical malformation of the hands manifested as a combination of syndactyly of the soft parts of the 3rd and 4th fingers and an incomplete bifurcation of the bones of the 4th finger."}
{"id": "PMID:212213", "title": "Chemical carcinogen alteration of SV40 virus induced transformation of normal human cell populations in vitro.", "content": "The frequency of simian papovirus 40 (SV40) induced transformation of human cells was enhanced after pretreatment with either napthylamine-2,N-methyl-N'-nitrosoguanidine (MNNG), N-acetyl-2-fluorenylacetamide (N-Ac-AAF), benzo[a]pyrene (BP), aflatoxin B1, propane sultone (PS), beta-propiolactone, 4-nitroquinoline oxide (4-NQO), methylmethane sulfonate (MMS) or diethyl nitrosamine (DEN). Posttreatment with 4-NQO, MMS, MNNG or DEN inhibited transformation; while posttreatment with either aflatoxin B1, beta-propiolactone or napthylamine-2 did not alter transformation similar to the action of N-Ac-AAF and BP. All carcinogens that altered transformation after pretreatment damaged cellular DNA. Pretreatment or posttreatment with carcinogens 3-methylcholanthrene (3-MCA) or 7,12-dimethylbenzanthrene (7,12-DMBA), that did not damage cellular DNA also did not enhance transformation. Moreover, pre- or posttreatment with other weak or non-carcinogens that did not damage cellular DNA did not alter virus induced transformation. All foci formed in the co-carcinogen treated cultures whether the carcinogen inhibited or enhanced transformation were virus directed. While a similar pattern of response existed for carcinogens that either enhance or inhibit transformation, each of the carcinogens that enhanced or inhibited foci formation damaged cellular DNA. Moreover, those carcinogens that enhanced focus formation, compared to the carcinogens that inhibited focus formation, exhibited similar DNA damage profiles.", "contents": "Chemical carcinogen alteration of SV40 virus induced transformation of normal human cell populations in vitro. The frequency of simian papovirus 40 (SV40) induced transformation of human cells was enhanced after pretreatment with either napthylamine-2,N-methyl-N'-nitrosoguanidine (MNNG), N-acetyl-2-fluorenylacetamide (N-Ac-AAF), benzo[a]pyrene (BP), aflatoxin B1, propane sultone (PS), beta-propiolactone, 4-nitroquinoline oxide (4-NQO), methylmethane sulfonate (MMS) or diethyl nitrosamine (DEN). Posttreatment with 4-NQO, MMS, MNNG or DEN inhibited transformation; while posttreatment with either aflatoxin B1, beta-propiolactone or napthylamine-2 did not alter transformation similar to the action of N-Ac-AAF and BP. All carcinogens that altered transformation after pretreatment damaged cellular DNA. Pretreatment or posttreatment with carcinogens 3-methylcholanthrene (3-MCA) or 7,12-dimethylbenzanthrene (7,12-DMBA), that did not damage cellular DNA also did not enhance transformation. Moreover, pre- or posttreatment with other weak or non-carcinogens that did not damage cellular DNA did not alter virus induced transformation. All foci formed in the co-carcinogen treated cultures whether the carcinogen inhibited or enhanced transformation were virus directed. While a similar pattern of response existed for carcinogens that either enhance or inhibit transformation, each of the carcinogens that enhanced or inhibited foci formation damaged cellular DNA. Moreover, those carcinogens that enhanced focus formation, compared to the carcinogens that inhibited focus formation, exhibited similar DNA damage profiles."}
{"id": "PMID:212214", "title": "Application of alkaline sucrose gradient sedimentation to the study of DNA damage and its repair in mammalian cells treated with methylmethanesulfonate and 4-nitroquinoline-1-oxide.", "content": "KB cells and L cells were treated with methylmethanesulfonate (MMS) or 4-nitroquinoline-1-oxide (4 NQO) and the resulting damage to DNA and its repair were examined by sedimentation in an alkaline sucrose gradient. The sedimentation profiles obtained were found to be the resultant of a complex interrelationship between drug dosage, duration of the lysis period and the repair capacity of the cells. A systematic study of these variables was made which led to a plausible and useful interpretation of the sedimentation profiles. Both drugs produce two kinds of DNA modifications which show up as a single-strand breaks but affect the sedimentation profile in characteristic ways. One of these modifications which is quite alkali-labile can be studied using a 30-min lysis period. The other modification is less alkali-labile and can be studied using a long lysis period. Both KB cells and L cells can repair the former type of damage but only KB cells can repair the latter type of damage.", "contents": "Application of alkaline sucrose gradient sedimentation to the study of DNA damage and its repair in mammalian cells treated with methylmethanesulfonate and 4-nitroquinoline-1-oxide. KB cells and L cells were treated with methylmethanesulfonate (MMS) or 4-nitroquinoline-1-oxide (4 NQO) and the resulting damage to DNA and its repair were examined by sedimentation in an alkaline sucrose gradient. The sedimentation profiles obtained were found to be the resultant of a complex interrelationship between drug dosage, duration of the lysis period and the repair capacity of the cells. A systematic study of these variables was made which led to a plausible and useful interpretation of the sedimentation profiles. Both drugs produce two kinds of DNA modifications which show up as a single-strand breaks but affect the sedimentation profile in characteristic ways. One of these modifications which is quite alkali-labile can be studied using a 30-min lysis period. The other modification is less alkali-labile and can be studied using a long lysis period. Both KB cells and L cells can repair the former type of damage but only KB cells can repair the latter type of damage."}
{"id": "PMID:212215", "title": "[Umbilical angiofibroma (apropos of a case)].", "content": "A woman aged 15 without any notable pathological history, was submitted to an operation because of a gradual growth of her umbilical region for a month. A tumor as large as an hazel-nut, was an angiofibroma of the round ligament of the liver. The round ligament may give cysts and tumors as the allantois does. If the tumors are generally malignant when situated in allantois, they would not always be mild when in the round ligament, as attested by a late observation in litterature.", "contents": "[Umbilical angiofibroma (apropos of a case)]. A woman aged 15 without any notable pathological history, was submitted to an operation because of a gradual growth of her umbilical region for a month. A tumor as large as an hazel-nut, was an angiofibroma of the round ligament of the liver. The round ligament may give cysts and tumors as the allantois does. If the tumors are generally malignant when situated in allantois, they would not always be mild when in the round ligament, as attested by a late observation in litterature."}
{"id": "PMID:212217", "title": "A study of filling defects in the liver and spleen with multiple radionuclides.", "content": "Studies were made to determine if examination with multiple radiopharmaceuticals would improve the sensitivity and specificity of colloid liver spleen scans. Increased uptake of Ga-67 citrate and In-111 bleomycin was found in most Tc-99m sulfur colloid scan defects caused by hepatocellular hepatoma or lymphoma. Increased uptake of these agents was found in some defects caused by malignant melanoma, breast carcinoma and carcinoma of the lung, and was rarely seen in defects caused by cholangiocarcinoma or gastrointestinal neoplasms. Gallium was useful in the followup of patients with hepatoma. Procedures designed to evaluate the gall bladder fossa, renal impression, or blood pool activity of an apparent tumor were found to be helpful and simple to perform. Iodine-131 as NaI was useful in studying functioning liver metastases from thyroid carcinoma as were bone scanning agents in evaluating hepatic metastases from osteogenic sarcoma. Multiple radiopharmaceutical evaluation of the physiologic and biochemical characteristics of liver lesions supplements current radiologic examinations and increases diagnostic specificity.", "contents": "A study of filling defects in the liver and spleen with multiple radionuclides. Studies were made to determine if examination with multiple radiopharmaceuticals would improve the sensitivity and specificity of colloid liver spleen scans. Increased uptake of Ga-67 citrate and In-111 bleomycin was found in most Tc-99m sulfur colloid scan defects caused by hepatocellular hepatoma or lymphoma. Increased uptake of these agents was found in some defects caused by malignant melanoma, breast carcinoma and carcinoma of the lung, and was rarely seen in defects caused by cholangiocarcinoma or gastrointestinal neoplasms. Gallium was useful in the followup of patients with hepatoma. Procedures designed to evaluate the gall bladder fossa, renal impression, or blood pool activity of an apparent tumor were found to be helpful and simple to perform. Iodine-131 as NaI was useful in studying functioning liver metastases from thyroid carcinoma as were bone scanning agents in evaluating hepatic metastases from osteogenic sarcoma. Multiple radiopharmaceutical evaluation of the physiologic and biochemical characteristics of liver lesions supplements current radiologic examinations and increases diagnostic specificity."}
{"id": "PMID:212219", "title": "Mechanism for lipid abnormalities of erythrocyte membranes in biliary obstruction: lecithin content and its fatty acyl composition.", "content": "The lipid compositions of erythrocyte membranes, plasma and bile of 16 patients with biliary obstruction were analysed to obtain information regarding the origin of excess lecithin which is usually found in the erythrocyte membranes in obstructive jaundice. Phospholipids and free cholesterol were found to be increased proportionally to the degree of biliary obstruction with an elevation in the free cholesterol/phospholipid ratio in the red cell membranes. The increase in phospholipid content is primarily due to lecithin. There was a highly significant alteration in the fatty acid composition of lecithin of erythrocyte membranes, plasma and bile from patients with severe jaundice. Red cell membrane lecithin amounted to more than 40% of the total phospholipid in these patients. Interestingly, the fatty acid composition of lecithin showed a similar pattern in erythrocyte membranes, plasma and bile. In addition, the fatty acyl chain composition of lecithin in lipoprotein-X was very similar to that of the red cell membrane. Freeze-fracture electron microscopy showed an alteration in membrane morphology and a reduced number of membrane-associated particles in the fractured faces. From these findings, we suggest that the lecithin of lipoprotein-X is derived from abnormal bile lecithin, which is incorporated into erythrocyte membranes by fusion with lipoprotein-X. On the other hand, the fatty acid composition of bile lecithin from patients with mild jaundice, whose erythrocyte membrane lecithin amounted to less than 31% of total phospholipid, was not different from that of normal individuals. However, in sharp contrast to the bile content, the fatty acid composition of erythrocyte membranes and plasma in these same patients showed a similar but small change compared to that of patients with severe biliary obstruction. The red cells of patients with mild jaundice were almost normal, biconcave disc-shaped, as observed by scanning electron microscopy and no abnormalities in the distribution or number of membrane particles were detected by freeze-fracturing. We propose that the abnormal lecithin content of erythrocyte membranes in patients with mild jaundice can be explained by the gradual exchange of lecithin between red blood cells and plasma lipoprotein.", "contents": "Mechanism for lipid abnormalities of erythrocyte membranes in biliary obstruction: lecithin content and its fatty acyl composition. The lipid compositions of erythrocyte membranes, plasma and bile of 16 patients with biliary obstruction were analysed to obtain information regarding the origin of excess lecithin which is usually found in the erythrocyte membranes in obstructive jaundice. Phospholipids and free cholesterol were found to be increased proportionally to the degree of biliary obstruction with an elevation in the free cholesterol/phospholipid ratio in the red cell membranes. The increase in phospholipid content is primarily due to lecithin. There was a highly significant alteration in the fatty acid composition of lecithin of erythrocyte membranes, plasma and bile from patients with severe jaundice. Red cell membrane lecithin amounted to more than 40% of the total phospholipid in these patients. Interestingly, the fatty acid composition of lecithin showed a similar pattern in erythrocyte membranes, plasma and bile. In addition, the fatty acyl chain composition of lecithin in lipoprotein-X was very similar to that of the red cell membrane. Freeze-fracture electron microscopy showed an alteration in membrane morphology and a reduced number of membrane-associated particles in the fractured faces. From these findings, we suggest that the lecithin of lipoprotein-X is derived from abnormal bile lecithin, which is incorporated into erythrocyte membranes by fusion with lipoprotein-X. On the other hand, the fatty acid composition of bile lecithin from patients with mild jaundice, whose erythrocyte membrane lecithin amounted to less than 31% of total phospholipid, was not different from that of normal individuals. However, in sharp contrast to the bile content, the fatty acid composition of erythrocyte membranes and plasma in these same patients showed a similar but small change compared to that of patients with severe biliary obstruction. The red cells of patients with mild jaundice were almost normal, biconcave disc-shaped, as observed by scanning electron microscopy and no abnormalities in the distribution or number of membrane particles were detected by freeze-fracturing. We propose that the abnormal lecithin content of erythrocyte membranes in patients with mild jaundice can be explained by the gradual exchange of lecithin between red blood cells and plasma lipoprotein."}
{"id": "PMID:212221", "title": "Low urinary oestrogen excretion during pregnancy, due to an impairment of fetal adrenocorticotrophic hormone secretion.", "content": "Four cases of newborn infants whose mothers had a low urinary oestrogen excretion during pregnancy are reported. Placental sulphatase deficiency in placental insufficiency were excluded by a dehydroepiandrosterone sulphate loading test. Postnatally, they developed a clinical picture characterized by an inappropriate secretion of cortisol which, by the results of an adrenocorticotrophic hormone stimulation test, appeared to be due to an impairment of adrenocorticotrophic hormone secretion. The prenatal and postnatal steroid metabolism is discussed.", "contents": "Low urinary oestrogen excretion during pregnancy, due to an impairment of fetal adrenocorticotrophic hormone secretion. Four cases of newborn infants whose mothers had a low urinary oestrogen excretion during pregnancy are reported. Placental sulphatase deficiency in placental insufficiency were excluded by a dehydroepiandrosterone sulphate loading test. Postnatally, they developed a clinical picture characterized by an inappropriate secretion of cortisol which, by the results of an adrenocorticotrophic hormone stimulation test, appeared to be due to an impairment of adrenocorticotrophic hormone secretion. The prenatal and postnatal steroid metabolism is discussed."}
{"id": "PMID:212222", "title": "Methods for the estimation of high density cholesterol, comparison between two laboratories.", "content": "The determination of HDL by quantification of HDL-cholesterol was investigated using different methods and employing the Abell method as reference. The routinely applied direct method of Huang (calibrated on Abell standardized sera) and the enzymatic method of R\u00f6schlau were tested. Results show that with the Huang method, as compared to Abell values, a total laboratory error of less than 4.5 mg/100 can be achieved in 95% of the cases. The enzymatic method gave rise to erroneous results. Comparisons between two laboratories in experiments using random and pool sera are presented.", "contents": "Methods for the estimation of high density cholesterol, comparison between two laboratories. The determination of HDL by quantification of HDL-cholesterol was investigated using different methods and employing the Abell method as reference. The routinely applied direct method of Huang (calibrated on Abell standardized sera) and the enzymatic method of R\u00f6schlau were tested. Results show that with the Huang method, as compared to Abell values, a total laboratory error of less than 4.5 mg/100 can be achieved in 95% of the cases. The enzymatic method gave rise to erroneous results. Comparisons between two laboratories in experiments using random and pool sera are presented."}
{"id": "PMID:212224", "title": "The vitamin D3 metabolite-type activity of Solanum malacoxylon.", "content": "1. Administration of an aqueous extract of the dried leaves of Solanum malacoxylon (DLSM) to rats causes a rapid hyperphosphataemia and a decrease in plasma alkaline phosphatase activity; the two effects are typical of 1,25(OH)2D3, the hormonally active metabolite of vitamin D3. 2. DLSM, like both vitamin D3 and parathyroid hormone, increases plasma calcium and citrate levels in rats. The effect of DLSM in influencing plasma citrate, and the role of this important metabolite in mineral metabolism is discussed. 3. A decrease of plasma magnesium levels occurs in rats following treatment with DLSM. This decrease, which is associated with a renal loss of this cation, is remarkably similar to that produced by hypervitaminosis D3. 4. Prolonged administration of DLSM to vitamin D deficient rats causes a polyuria, hypercalciuria, hyperphosphaturia, hypermagnesuria, an increase in urinary total hydroxyproline, an increase in plasma total hexosamines, and a corresponding decrease in the bone total hexosamines. These effects, some of which can also be produced by hyperparathyroidism, or following the administration of parathyroid extract (PTE), large doses of vitamin D3, or 1,25(OH)2D3, suggest that DLSM, like the latter compounds, is capable of causing bone mineral mobilization, and the dissolution of bone organic matrix.", "contents": "The vitamin D3 metabolite-type activity of Solanum malacoxylon. 1. Administration of an aqueous extract of the dried leaves of Solanum malacoxylon (DLSM) to rats causes a rapid hyperphosphataemia and a decrease in plasma alkaline phosphatase activity; the two effects are typical of 1,25(OH)2D3, the hormonally active metabolite of vitamin D3. 2. DLSM, like both vitamin D3 and parathyroid hormone, increases plasma calcium and citrate levels in rats. The effect of DLSM in influencing plasma citrate, and the role of this important metabolite in mineral metabolism is discussed. 3. A decrease of plasma magnesium levels occurs in rats following treatment with DLSM. This decrease, which is associated with a renal loss of this cation, is remarkably similar to that produced by hypervitaminosis D3. 4. Prolonged administration of DLSM to vitamin D deficient rats causes a polyuria, hypercalciuria, hyperphosphaturia, hypermagnesuria, an increase in urinary total hydroxyproline, an increase in plasma total hexosamines, and a corresponding decrease in the bone total hexosamines. These effects, some of which can also be produced by hyperparathyroidism, or following the administration of parathyroid extract (PTE), large doses of vitamin D3, or 1,25(OH)2D3, suggest that DLSM, like the latter compounds, is capable of causing bone mineral mobilization, and the dissolution of bone organic matrix."}
{"id": "PMID:212225", "title": "The chemistry and conformational and biological analysis of vitamin D3, its metabolites and analogues.", "content": "The chemical properties, stereochemical relationships and solution conformation, as assessed in part by proton NMR spectroscopy, for vitamin D3, its major metabolites [including 1alpha,25-(OH)2D3, its hormonally active form] and a number of A-ring and side chain analogues are evaluated and discussed in relation to their biological activity. In particular the relative ability of many of these seco-steroids to compete both with 25-OHD3 for its chick serum binding protein and 1alpha,25-(OH)2-D3 for its chick intestinal cytosol-chromatin receptor system was quantitated, in vitro. Further, the relative effectiveness of all these metabolites and analogues to mediate in vivo intestinal calcium absorption and bone calcium mobilization was determined. Collectively these chemical and biological studies constitute a \"systems analysis\" of the various steroid structural parameters both required and tolerated by the multi-stepped endocrine system associated with the biological actions of vitamin D.", "contents": "The chemistry and conformational and biological analysis of vitamin D3, its metabolites and analogues. The chemical properties, stereochemical relationships and solution conformation, as assessed in part by proton NMR spectroscopy, for vitamin D3, its major metabolites [including 1alpha,25-(OH)2D3, its hormonally active form] and a number of A-ring and side chain analogues are evaluated and discussed in relation to their biological activity. In particular the relative ability of many of these seco-steroids to compete both with 25-OHD3 for its chick serum binding protein and 1alpha,25-(OH)2-D3 for its chick intestinal cytosol-chromatin receptor system was quantitated, in vitro. Further, the relative effectiveness of all these metabolites and analogues to mediate in vivo intestinal calcium absorption and bone calcium mobilization was determined. Collectively these chemical and biological studies constitute a \"systems analysis\" of the various steroid structural parameters both required and tolerated by the multi-stepped endocrine system associated with the biological actions of vitamin D."}
{"id": "PMID:212227", "title": "The assay of 1alpha,25-dihydroxyvitamin D3: physiologic and pathologic modulation of circulating hormone levels.", "content": "A sensitive radioreceptor assay for 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) is utilized to quantitate the circulating concentration of this sterol in experimental animals and humans. When weanling rats are grown for 2 weeks on low calcium or low phosphate diets, limited availability of either ion elicits a five-fold increase in the plasma level of 1alpha,25-(OH)2D3. The enhancement of 1alpha,25-(OH)2D3 in calcium deficiency is dependent upon the presence of the parathyroid and/or thyroid glands, which is consistent with parathyroid hormone (PTH) mediation of this effect. In contrast, the response to phosphate deficiency is independent of these glands and may result from a direct action of low phosphate on the renal synthesis of 1alpha,25-(OH)2D3. Studies in humans indicate that the normal level of 1alpha,25-(OH)2D is 2.1--4.5 ng/100 ml plasma. Patients with chronic renal failure have markedly lower circulating 1alpha,25-(OH)2D and this kidney hormone is undetectable in anephric subjects, but returns to normal within 1 day after successful renal transplantation. Hypoparathyroidism and pseudohypoparathyroidism are associated with reduced plasma 1alpha,25-(OH)2D while patients with primary hyperparathyroidism have significantly elevated sterol hormone levels. Thus, from measurements in rats and humans, it appears that circulating 1alpha,25-(OH)2D3 is regulated by PTH and/or phosphate and that abnormal plasma 1alpha,25-(OH)2D3 is a part of the pathophysiology of renal osteodystrophy and parathyroid disorders.", "contents": "The assay of 1alpha,25-dihydroxyvitamin D3: physiologic and pathologic modulation of circulating hormone levels. A sensitive radioreceptor assay for 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) is utilized to quantitate the circulating concentration of this sterol in experimental animals and humans. When weanling rats are grown for 2 weeks on low calcium or low phosphate diets, limited availability of either ion elicits a five-fold increase in the plasma level of 1alpha,25-(OH)2D3. The enhancement of 1alpha,25-(OH)2D3 in calcium deficiency is dependent upon the presence of the parathyroid and/or thyroid glands, which is consistent with parathyroid hormone (PTH) mediation of this effect. In contrast, the response to phosphate deficiency is independent of these glands and may result from a direct action of low phosphate on the renal synthesis of 1alpha,25-(OH)2D3. Studies in humans indicate that the normal level of 1alpha,25-(OH)2D is 2.1--4.5 ng/100 ml plasma. Patients with chronic renal failure have markedly lower circulating 1alpha,25-(OH)2D and this kidney hormone is undetectable in anephric subjects, but returns to normal within 1 day after successful renal transplantation. Hypoparathyroidism and pseudohypoparathyroidism are associated with reduced plasma 1alpha,25-(OH)2D while patients with primary hyperparathyroidism have significantly elevated sterol hormone levels. Thus, from measurements in rats and humans, it appears that circulating 1alpha,25-(OH)2D3 is regulated by PTH and/or phosphate and that abnormal plasma 1alpha,25-(OH)2D3 is a part of the pathophysiology of renal osteodystrophy and parathyroid disorders."}
{"id": "PMID:212228", "title": "VIP measurement in distinguishing Verner-Morrison syndrome and pseudo Verner-Morrison syndrome.", "content": "1. Plasma VIP immunoreactivity is always diagnostically raised in patients with pancreatic tumour causing the Verner-Morrison syndrome. 2. Human tumour VIP is physico-chemically similar to porcine VIP. 3. The only other situation in which plasma VIP is very elevated is in patients with ganglioneuroblastomas associated with diarrhoea. 4. VIP is not elevated in patients with diarrhoea associated with pancreatic islet hyperplasia, designated the pseudo Verner-Morrison syndrome.", "contents": "VIP measurement in distinguishing Verner-Morrison syndrome and pseudo Verner-Morrison syndrome. 1. Plasma VIP immunoreactivity is always diagnostically raised in patients with pancreatic tumour causing the Verner-Morrison syndrome. 2. Human tumour VIP is physico-chemically similar to porcine VIP. 3. The only other situation in which plasma VIP is very elevated is in patients with ganglioneuroblastomas associated with diarrhoea. 4. VIP is not elevated in patients with diarrhoea associated with pancreatic islet hyperplasia, designated the pseudo Verner-Morrison syndrome."}
{"id": "PMID:212229", "title": "Mode of action of peptide hormones.", "content": "The mode of action is discussed of the peptide hormones which trigger neosynthesis of a specific product in their target cells without being involved in any release step. Particular attention is paid to the early events elicited by ACTH in isolated adrenocortical cells. It is shown that extracellular calcium ions at physiological concentrations can serve as first messenger activating steroidogenesis if the isolated cells are pretreated in an appropriate ionic environment. Among other factors the extracellular calcium/phosphate ratio seems to be of importance. A model is proposed where calcium serves as direct messenger in the physiological activation by ACTH, cyclic AMP being a subserving factor maintaining full steroidogenesis.", "contents": "Mode of action of peptide hormones. The mode of action is discussed of the peptide hormones which trigger neosynthesis of a specific product in their target cells without being involved in any release step. Particular attention is paid to the early events elicited by ACTH in isolated adrenocortical cells. It is shown that extracellular calcium ions at physiological concentrations can serve as first messenger activating steroidogenesis if the isolated cells are pretreated in an appropriate ionic environment. Among other factors the extracellular calcium/phosphate ratio seems to be of importance. A model is proposed where calcium serves as direct messenger in the physiological activation by ACTH, cyclic AMP being a subserving factor maintaining full steroidogenesis."}
{"id": "PMID:212230", "title": "Concepts in ectopic hormone production.", "content": "Non-endocrine tumours are capable of production of ectopic hormones, precursor molecules subunits and hormone-related fragments. The measurement of these may provide biochemical markers of malignancy, allowing presymptomatic diagnosis which may lead ultimately to an improved prognosis for the patient. The study of ectopic humoral syndromes may yield new insights into the nature of cellular differentation and the fundamental process of malignant change.", "contents": "Concepts in ectopic hormone production. Non-endocrine tumours are capable of production of ectopic hormones, precursor molecules subunits and hormone-related fragments. The measurement of these may provide biochemical markers of malignancy, allowing presymptomatic diagnosis which may lead ultimately to an improved prognosis for the patient. The study of ectopic humoral syndromes may yield new insights into the nature of cellular differentation and the fundamental process of malignant change."}
{"id": "PMID:212231", "title": "Hormone receptors and cyclic nucleotide metabolism in cancer cells.", "content": "The possibility of a relationship between cyclic AMP formation and metabolic processes in tumours has been investigated. Changes in basal activity and hormone-responsiveness of adenylate cyclase were demonstrated in plasma membranes and intact cells from pre-cancerous liver of rats fed a diet containing the carcinogen 3'-methyl-4-dimethylaminoazobenzene. Basal adenylate cyclase activity in hyperplastic parathyroid gland membranes was 200% higher than that in parathyroid adenoma membranes, corresponding with their relative rates of parathyroid hormone secretion in vitro. Membrane adenylate cyclase activity in hypernephromas was consistently 100--300% higher than in adjacent human renal cortex. Furthermore the adenylate cyclase activity of the tumour membranes was not influenced by a wide range of hormones which were effective stimulants in 'normal' renal cortex membranes. Conversion of 25-hydroxycholecalciferol to 1,25-dihydrocholecalciferol could not be demonstrated in either hypernephroma or adjacent renal cortical tissue. However, three of the four hypernephromas tested secreted a bone-resorbing factor. Cyclic AMP formation was increased by salmon, human and porcine calcitonins in both plasma membranes and intact cells from a poorly differentiated epidermoid cell carcinoma which was itself secreting calcitonin in culture. This phenomenon might be related to a feedback regulation of calcitonin production in this cell line. The observations are consistent with the concept of a relationship between cyclic AMP formation and certain metabolic functions (e.g. hormone production) in tumour cells.", "contents": "Hormone receptors and cyclic nucleotide metabolism in cancer cells. The possibility of a relationship between cyclic AMP formation and metabolic processes in tumours has been investigated. Changes in basal activity and hormone-responsiveness of adenylate cyclase were demonstrated in plasma membranes and intact cells from pre-cancerous liver of rats fed a diet containing the carcinogen 3'-methyl-4-dimethylaminoazobenzene. Basal adenylate cyclase activity in hyperplastic parathyroid gland membranes was 200% higher than that in parathyroid adenoma membranes, corresponding with their relative rates of parathyroid hormone secretion in vitro. Membrane adenylate cyclase activity in hypernephromas was consistently 100--300% higher than in adjacent human renal cortex. Furthermore the adenylate cyclase activity of the tumour membranes was not influenced by a wide range of hormones which were effective stimulants in 'normal' renal cortex membranes. Conversion of 25-hydroxycholecalciferol to 1,25-dihydrocholecalciferol could not be demonstrated in either hypernephroma or adjacent renal cortical tissue. However, three of the four hypernephromas tested secreted a bone-resorbing factor. Cyclic AMP formation was increased by salmon, human and porcine calcitonins in both plasma membranes and intact cells from a poorly differentiated epidermoid cell carcinoma which was itself secreting calcitonin in culture. This phenomenon might be related to a feedback regulation of calcitonin production in this cell line. The observations are consistent with the concept of a relationship between cyclic AMP formation and certain metabolic functions (e.g. hormone production) in tumour cells."}
{"id": "PMID:212232", "title": "Ectopic hormone production by bronchial carcinomas in culture.", "content": "Monolayer tissue culture has been used as a system in which to study aspects of ectopic hormone secretion. Of a series of twenty-four human bronchial carcinomas, nineteen were successfully established in culture and the supernatant medium from each tested for peptide hormones by radioimmunoassay. Six tumours were found to produce adrenocorticotrophin (ACTH), four to release calcitonin (CT) and one to release both of these hormones. No growth hormone or insulin was detected throughout the series. Net in vitro synthesis of both ACTH and CT was demonstrated by recovery of more hormone during culture than was originally contained in the explanted tumour tissue. The production of hormone by four out of six proliferative cultures established, and its persistence through many subculture passages, confirms ectopic hormone production as a stable heritable characteristic of some lung tumours. The ability of hormone-producing bronchial tumour cells to respond to factors known to influence hormone output from normal endocrine cells was tested. ACTH release was stimulated in one tumour by Pitressin and CT in another by gastrin. In addition, the release of CT from the same tumour cell line was shown to be inhibited by the accumulation of high external concentrations of CT as has been reported for normal C-cells.", "contents": "Ectopic hormone production by bronchial carcinomas in culture. Monolayer tissue culture has been used as a system in which to study aspects of ectopic hormone secretion. Of a series of twenty-four human bronchial carcinomas, nineteen were successfully established in culture and the supernatant medium from each tested for peptide hormones by radioimmunoassay. Six tumours were found to produce adrenocorticotrophin (ACTH), four to release calcitonin (CT) and one to release both of these hormones. No growth hormone or insulin was detected throughout the series. Net in vitro synthesis of both ACTH and CT was demonstrated by recovery of more hormone during culture than was originally contained in the explanted tumour tissue. The production of hormone by four out of six proliferative cultures established, and its persistence through many subculture passages, confirms ectopic hormone production as a stable heritable characteristic of some lung tumours. The ability of hormone-producing bronchial tumour cells to respond to factors known to influence hormone output from normal endocrine cells was tested. ACTH release was stimulated in one tumour by Pitressin and CT in another by gastrin. In addition, the release of CT from the same tumour cell line was shown to be inhibited by the accumulation of high external concentrations of CT as has been reported for normal C-cells."}
{"id": "PMID:212233", "title": "Hormone-receptor interactions. The message sequence of alpha-melanotropin: demonstration of two active sites.", "content": "The purpose of this investigation was to elucidate the biological significance of lysine11 and of the tripeptide sequence =Lys-Pro-Val-NH2 for the biological activity of alpha-melanocyte-stimulating hormone. To this end the in vitro melanotropic activities of twenty-four synthetic peptides related to the hormone were determined. Extension or reduction of the length of the lysine11 side chain results in a marked decrease of the melanotropic potency of the respective analogue. The C-terminal tripeptide (11--13), the tetrapeptide (10--13), and the pentapeptide (9--13) were found to be hormonally active in the same order of magnitude as the central hexapeptide (5--10). The following conclusion was drawn: alpha-MSH possesses (in contrast to ACTH) two message sequences (active sites), (i)-Glu-His-Phe-Arg-Trp-, and (ii)-Gly-Lys-Pro-Val-NH2 which are capable of independently triggering the hormone receptor responsible for melanin dispersion. Thus, despite the close structural similarity of the two hormones, alpha-MSH and ACTH appear to react with their respective target cell receptors by quite different chemical mechanisms, implying different receptor structures.", "contents": "Hormone-receptor interactions. The message sequence of alpha-melanotropin: demonstration of two active sites. The purpose of this investigation was to elucidate the biological significance of lysine11 and of the tripeptide sequence =Lys-Pro-Val-NH2 for the biological activity of alpha-melanocyte-stimulating hormone. To this end the in vitro melanotropic activities of twenty-four synthetic peptides related to the hormone were determined. Extension or reduction of the length of the lysine11 side chain results in a marked decrease of the melanotropic potency of the respective analogue. The C-terminal tripeptide (11--13), the tetrapeptide (10--13), and the pentapeptide (9--13) were found to be hormonally active in the same order of magnitude as the central hexapeptide (5--10). The following conclusion was drawn: alpha-MSH possesses (in contrast to ACTH) two message sequences (active sites), (i)-Glu-His-Phe-Arg-Trp-, and (ii)-Gly-Lys-Pro-Val-NH2 which are capable of independently triggering the hormone receptor responsible for melanin dispersion. Thus, despite the close structural similarity of the two hormones, alpha-MSH and ACTH appear to react with their respective target cell receptors by quite different chemical mechanisms, implying different receptor structures."}
{"id": "PMID:212234", "title": "On the metabolism of two adrenocorticotrophin analogues.", "content": "The metabolism of Synacthen (corticotrophin-(1--24)-tetracosapeptide) and C-41795-Ba ([D-Ser1,Lys17,Lys18]-corticotrophin-(1--18)-octadecapeptide amide) have been compared in the rat following intravenous injection. Using Synacthen and C-41795-Ba labelled with tritium it was possible to follow the tissue distribution of the two peptides. The kidney was shown to concentrate intact peptide and fragments of both peptides. Autoradiography of perfused kidney sections demonstrated the uptake of radioactivity into the lysosomes of the kidney proximal tubule cells. Comparison of the distribution of radioactive products formed from the tetracosapeptide labelled in different positions indicates that, prior to renal uptake, metabolism is taking place at other sites in the body. It is suggested that rapid cleavage occurs extracellularly at or near the N- and C-termini. Then large fragments remaining in the circulation, together with any intact material, are filtered through the glomerulus and are taken up by endocytosis into the proximal tubule cells of the kidney. The synthetic N- and C-terminal protection of the octadecapeptide appears to inhibit the extracellular attack and so the concentration of intact peptide in the kidneys is initially higher than the tetracosapeptide. Although concentrations of radioactivity in other tissues are low in comparison with the kidneys, the quantities are quite high when the weight of the tissues are considered. Chromatographic analysis of this radioactivity reveals that the octadecapeptide gives rise to much higher tissue levels of intact peptide and we believe that this acts as a depot and gives rise to the sustained blood concentrations and prolonged biological effects observed with this peptide.", "contents": "On the metabolism of two adrenocorticotrophin analogues. The metabolism of Synacthen (corticotrophin-(1--24)-tetracosapeptide) and C-41795-Ba ([D-Ser1,Lys17,Lys18]-corticotrophin-(1--18)-octadecapeptide amide) have been compared in the rat following intravenous injection. Using Synacthen and C-41795-Ba labelled with tritium it was possible to follow the tissue distribution of the two peptides. The kidney was shown to concentrate intact peptide and fragments of both peptides. Autoradiography of perfused kidney sections demonstrated the uptake of radioactivity into the lysosomes of the kidney proximal tubule cells. Comparison of the distribution of radioactive products formed from the tetracosapeptide labelled in different positions indicates that, prior to renal uptake, metabolism is taking place at other sites in the body. It is suggested that rapid cleavage occurs extracellularly at or near the N- and C-termini. Then large fragments remaining in the circulation, together with any intact material, are filtered through the glomerulus and are taken up by endocytosis into the proximal tubule cells of the kidney. The synthetic N- and C-terminal protection of the octadecapeptide appears to inhibit the extracellular attack and so the concentration of intact peptide in the kidneys is initially higher than the tetracosapeptide. Although concentrations of radioactivity in other tissues are low in comparison with the kidneys, the quantities are quite high when the weight of the tissues are considered. Chromatographic analysis of this radioactivity reveals that the octadecapeptide gives rise to much higher tissue levels of intact peptide and we believe that this acts as a depot and gives rise to the sustained blood concentrations and prolonged biological effects observed with this peptide."}
{"id": "PMID:212235", "title": "Regulation of vitamin D: an evolutionary view.", "content": "The regulation of vitamin D metabolism by the kidney is now known to be multifactorial. Three regulatory factors are discussed: 1,25(OH)2D3 itself; parathyroid hormone, and phospate. The influence of 1,25(OH)2D3 probably depends on new protein synthesis, while the mode of action of phosphate is unknown. Parathyroid hormone is not essential for regulation but may have an important biological role. The direction of its effect varies, perhaps due to a complex interrelation of changes in calcium and phosphorus metabolism and the level of kidney adenyl cyclase activity.", "contents": "Regulation of vitamin D: an evolutionary view. The regulation of vitamin D metabolism by the kidney is now known to be multifactorial. Three regulatory factors are discussed: 1,25(OH)2D3 itself; parathyroid hormone, and phospate. The influence of 1,25(OH)2D3 probably depends on new protein synthesis, while the mode of action of phosphate is unknown. Parathyroid hormone is not essential for regulation but may have an important biological role. The direction of its effect varies, perhaps due to a complex interrelation of changes in calcium and phosphorus metabolism and the level of kidney adenyl cyclase activity."}
{"id": "PMID:212238", "title": "A possible ACTH secreting tumour of the pituitary developing in a conventionally treated case of Addison's disease.", "content": "A patient with Addison's disease, treated with conventional corticosteroid therapy, developed endocrine and radiological features suggestive of an ACTH secreting pituitary tumour. The negative feedback control of ACTH secretion by the inhibitory effect of hydrocortisone was shown to be preserved although attenuated. Retiming and alteration of corticosteroid therapy reinforced this feedback control, without the need for supraphysiological amounts of steroid, and resulted in the regression of the endocrine disorder.", "contents": "A possible ACTH secreting tumour of the pituitary developing in a conventionally treated case of Addison's disease. A patient with Addison's disease, treated with conventional corticosteroid therapy, developed endocrine and radiological features suggestive of an ACTH secreting pituitary tumour. The negative feedback control of ACTH secretion by the inhibitory effect of hydrocortisone was shown to be preserved although attenuated. Retiming and alteration of corticosteroid therapy reinforced this feedback control, without the need for supraphysiological amounts of steroid, and resulted in the regression of the endocrine disorder."}
{"id": "PMID:212239", "title": "Stimulation of amniotic fluid cells by fibroblast growth factor.", "content": "Amniotic fluid cells were grown in modified Dulbecco's medium with and without the following additives in different combinations: fibroblast growth factor (FGF), dexamethasone (DME), insulin and cyclic GMP under controlled conditions. Experiments were also conducted with varying amounts of foetal calf serum and FGF to establish optimum levels. Comparative growth, determined by measuring 3H-thymidine uptake, showed that the combination of FGF, DME and insulin in medium with 20% foetal calf serum produced the highest growth rate. These experiments indicate that the culture time of amniotic fluid cells for chromosome studies could be reduced by 25%. FGF did not have any deleterious effect on the chromosomes.", "contents": "Stimulation of amniotic fluid cells by fibroblast growth factor. Amniotic fluid cells were grown in modified Dulbecco's medium with and without the following additives in different combinations: fibroblast growth factor (FGF), dexamethasone (DME), insulin and cyclic GMP under controlled conditions. Experiments were also conducted with varying amounts of foetal calf serum and FGF to establish optimum levels. Comparative growth, determined by measuring 3H-thymidine uptake, showed that the combination of FGF, DME and insulin in medium with 20% foetal calf serum produced the highest growth rate. These experiments indicate that the culture time of amniotic fluid cells for chromosome studies could be reduced by 25%. FGF did not have any deleterious effect on the chromosomes."}
{"id": "PMID:212243", "title": "Alteration of body distribution of 99mTc-pyrophosphate by radiographic contrast material.", "content": "Abnormal distribution of 99mTc-PYP was found in an elderly patient who had received 100 ml of radiographic contrast material between the time of injection of the radiopharmaceutical and the performance of the bone scan. Reasons for these alterations are postulated.", "contents": "Alteration of body distribution of 99mTc-pyrophosphate by radiographic contrast material. Abnormal distribution of 99mTc-PYP was found in an elderly patient who had received 100 ml of radiographic contrast material between the time of injection of the radiopharmaceutical and the performance of the bone scan. Reasons for these alterations are postulated."}
{"id": "PMID:212246", "title": "Effect of unconjugated and conjugated phenol and uraemia on the synthesis of adenosine 3' :5' -cyclic monophosphate in rat brain homogenates.", "content": "1. The effects of phenol and phenyl glucuronide on the responses of normal rat brain adenyl cyclase to noradrenaline and dopamine have been investigated. Neurotransmitter responses have also been examined in brains from uraemic and normal rats. 2. A depressive effect of phenol on the adenosine 3' :5' -cyclic monophosphate response of the neostriatum to dopamine was shown to be completely abolished if the toxin was present in the conjugated form; the response of the cortex to noradrenaline was stimulated by the presence of phenyl glucuronide, even though the unconjugated form had no effect. 3. The uraemic state in the rat also resulted in a depression of the neostriatum response to dopamine, yet an enhancement of the cortical response to noradrenaline. 4. The action of phenols of the brain is relevant to hepatic and uraemic coma.", "contents": "Effect of unconjugated and conjugated phenol and uraemia on the synthesis of adenosine 3' :5' -cyclic monophosphate in rat brain homogenates. 1. The effects of phenol and phenyl glucuronide on the responses of normal rat brain adenyl cyclase to noradrenaline and dopamine have been investigated. Neurotransmitter responses have also been examined in brains from uraemic and normal rats. 2. A depressive effect of phenol on the adenosine 3' :5' -cyclic monophosphate response of the neostriatum to dopamine was shown to be completely abolished if the toxin was present in the conjugated form; the response of the cortex to noradrenaline was stimulated by the presence of phenyl glucuronide, even though the unconjugated form had no effect. 3. The uraemic state in the rat also resulted in a depression of the neostriatum response to dopamine, yet an enhancement of the cortical response to noradrenaline. 4. The action of phenols of the brain is relevant to hepatic and uraemic coma."}
{"id": "PMID:212250", "title": "Use of 99Tcm-DMSA as a static renal imaging agent.", "content": "The use of 99Tcm-labelled DMSA as a static renal imaging agent has been analyzed semi-quantitatively in 366 patients. Study with this agent proved to be of most value in patients with equivocal space-occupying lesions of the kidney, provided useful information in various destructive diseases of the kidney when used for determining divided renal function but was of little value in chronic renal failure. In 33 patients, the uptake of 99Tcm-DMSA at 3 h as a measure of divided renal function was compared with the uptake of 99Tcm-DTPA from 30 to 150 sec following injection and was found to correlate well. In a series of 7 dogs with induced unilateral renal impairment, divided function determined with 99Tcm-DMSA was found to correlate well with results obtained using 51Cr-EDTA.", "contents": "Use of 99Tcm-DMSA as a static renal imaging agent. The use of 99Tcm-labelled DMSA as a static renal imaging agent has been analyzed semi-quantitatively in 366 patients. Study with this agent proved to be of most value in patients with equivocal space-occupying lesions of the kidney, provided useful information in various destructive diseases of the kidney when used for determining divided renal function but was of little value in chronic renal failure. In 33 patients, the uptake of 99Tcm-DMSA at 3 h as a measure of divided renal function was compared with the uptake of 99Tcm-DTPA from 30 to 150 sec following injection and was found to correlate well. In a series of 7 dogs with induced unilateral renal impairment, divided function determined with 99Tcm-DMSA was found to correlate well with results obtained using 51Cr-EDTA."}
{"id": "PMID:212251", "title": "Cellular interactions between vasopressin and prostaglandins in the mammalian kidney.", "content": "Current experimental evidence indicates that endogenous renal medullary prostaglandins modulate the antidiuretic response to vasopressin in the mammalian kidney. The predominant effect of prostaglandins is to attenuate the antidiuretic response to vasopressin; inhibition of prostaglandin synthesis potentiates the renal effect of vasopressin. Prostaglandins likely antagonize the renal effects of vasopressin at the cellular level of hormone-dependent cyclic adenosine 3,5-monophosphate metabolism, but the exact molecular mechanism is not known. Likewise, it is not known whether such modulatory effect is due to primary prostaglandins, prostaglandin precursors or to other metabolites of arachidonic acid. Vasopressin itself could stimulate intrarenal prostaglandin synthesis; this effect may represent a negative-feedback regulatory pathway for the antidiuretic response to the hormone. Recent experimental evidence suggests that modulatory effect of prostaglandin may be a factor in pathogenesis of some types of urinary concentrating defects.", "contents": "Cellular interactions between vasopressin and prostaglandins in the mammalian kidney. Current experimental evidence indicates that endogenous renal medullary prostaglandins modulate the antidiuretic response to vasopressin in the mammalian kidney. The predominant effect of prostaglandins is to attenuate the antidiuretic response to vasopressin; inhibition of prostaglandin synthesis potentiates the renal effect of vasopressin. Prostaglandins likely antagonize the renal effects of vasopressin at the cellular level of hormone-dependent cyclic adenosine 3,5-monophosphate metabolism, but the exact molecular mechanism is not known. Likewise, it is not known whether such modulatory effect is due to primary prostaglandins, prostaglandin precursors or to other metabolites of arachidonic acid. Vasopressin itself could stimulate intrarenal prostaglandin synthesis; this effect may represent a negative-feedback regulatory pathway for the antidiuretic response to the hormone. Recent experimental evidence suggests that modulatory effect of prostaglandin may be a factor in pathogenesis of some types of urinary concentrating defects."}
{"id": "PMID:212252", "title": "The kallikrein-kinin system in the kidney.", "content": "To understand the role of the kallikrein-kinin system in the kidney all components of the system and their localization need to be considered. About half the kallikrein in urine occurs as the proenzyme which arises in the distal tubule. Kinins are formed in the distal tubule and collecting duct from urokinnogen which is found throughout the tubule. Urine contains about twice as much lysyl-brandykinin as bradykinin. A third kinin, methionyl-lysyl-bradykinin, also can occur in urine. It is probably produced by uropepsin as the kinin is largely formed in acidified urine and its formation is inhibited by pepstatin. The significance of the three kinins is unknown. Kinins are normally slowly (few hours) destroyed in urine. The importance of kallikrein, urokinogen and kininases in regulating the level of kinins needs to be determined.", "contents": "The kallikrein-kinin system in the kidney. To understand the role of the kallikrein-kinin system in the kidney all components of the system and their localization need to be considered. About half the kallikrein in urine occurs as the proenzyme which arises in the distal tubule. Kinins are formed in the distal tubule and collecting duct from urokinnogen which is found throughout the tubule. Urine contains about twice as much lysyl-brandykinin as bradykinin. A third kinin, methionyl-lysyl-bradykinin, also can occur in urine. It is probably produced by uropepsin as the kinin is largely formed in acidified urine and its formation is inhibited by pepstatin. The significance of the three kinins is unknown. Kinins are normally slowly (few hours) destroyed in urine. The importance of kallikrein, urokinogen and kininases in regulating the level of kinins needs to be determined."}
{"id": "PMID:212255", "title": "Contribution to the problem of the relationship of infection and rejection in patients with kidney transplants.", "content": "The paper deals with the incidence of infectious complications and rejection crises in patients with renal transplants. It was revealed by statistical methods that there exists a certain correlation between infections and rejections, which depends on the type of the infectious agent. In patients where infectious complications were caused only by gram-negative flora an indirect relationship was revealed, while in patients with infectious complications where gram-positive flora, viruses or fungi participated, a marked direct correlation was found. Statistical methods proved also a higher incidence of rejection crises in patients with active cytomegalic infection.", "contents": "Contribution to the problem of the relationship of infection and rejection in patients with kidney transplants. The paper deals with the incidence of infectious complications and rejection crises in patients with renal transplants. It was revealed by statistical methods that there exists a certain correlation between infections and rejections, which depends on the type of the infectious agent. In patients where infectious complications were caused only by gram-negative flora an indirect relationship was revealed, while in patients with infectious complications where gram-positive flora, viruses or fungi participated, a marked direct correlation was found. Statistical methods proved also a higher incidence of rejection crises in patients with active cytomegalic infection."}
{"id": "PMID:212257", "title": "Granular-cell tumors (myoblastomas) of the anal region.", "content": "Three cases of granular-cell tumor of the perianal region are reported. The clinical and pathologic features of these tumors are reviewed. Their precise histogenesis remains uncertain. The association with pseudoepitheliomatous hyperplasia of the overlying epithelium, which was well illustrated in two of the three cases, is discussed. The lesions are nearly always benign, and the treatment of choice is local excision.", "contents": "Granular-cell tumors (myoblastomas) of the anal region. Three cases of granular-cell tumor of the perianal region are reported. The clinical and pathologic features of these tumors are reviewed. Their precise histogenesis remains uncertain. The association with pseudoepitheliomatous hyperplasia of the overlying epithelium, which was well illustrated in two of the three cases, is discussed. The lesions are nearly always benign, and the treatment of choice is local excision."}
{"id": "PMID:212258", "title": "Submucosal tumors of the colon: experience with twenty-five cases.", "content": "Submucosal tumors of the colon are rare and require alertness on the part of the physician for early diagnosis. These tumors may not cause symptoms before attaining large size. In most cases the clinical histories are atypical. Because of the possibility of malignancy, adequate diagnosis and treatment are necessary. This report deals with 25 cases of submucosal tumors of the colon. The tumor series included seven leiomyomas, one granular-cell myoblastoma, two leiomyosarcomas, seven carcinoid tumors, six lipomas, one lymphangioma, and one neurofibroma. Five of the tumors were asymptomatic. The endoscopic appearances of the tumors, although not diagnostic, may give some indications as to their natures. Endoscopic removal is possible, although it is indicated for high-risk patients only. Because submucosal tumors may be malignant, and because differentiation from secondary tumors (metastases) or tumor-like lesions is difficult without histologic examination, complete removal of the tumor is the treatment of choice.", "contents": "Submucosal tumors of the colon: experience with twenty-five cases. Submucosal tumors of the colon are rare and require alertness on the part of the physician for early diagnosis. These tumors may not cause symptoms before attaining large size. In most cases the clinical histories are atypical. Because of the possibility of malignancy, adequate diagnosis and treatment are necessary. This report deals with 25 cases of submucosal tumors of the colon. The tumor series included seven leiomyomas, one granular-cell myoblastoma, two leiomyosarcomas, seven carcinoid tumors, six lipomas, one lymphangioma, and one neurofibroma. Five of the tumors were asymptomatic. The endoscopic appearances of the tumors, although not diagnostic, may give some indications as to their natures. Endoscopic removal is possible, although it is indicated for high-risk patients only. Because submucosal tumors may be malignant, and because differentiation from secondary tumors (metastases) or tumor-like lesions is difficult without histologic examination, complete removal of the tumor is the treatment of choice."}
{"id": "PMID:212256", "title": "Multiple granular-cell tumors of the ascending colon: microscopic study.", "content": "Light and electron microscopic study of a case of multiple granular-cell tumor of the ascending colon is presented, and the relevant medical literature is reviewed. It seems that the biologic behavior of this tumor in the colon does not differ from that in other locations. Histologically, a few granular cells are seen in neural tissue in the vicinity of the tumor, suggesting a close relation of the tumor to the neural tissue. Electron-microscopically, the granular cells resemble Schwann cells more closely than neural cells and axons. Histochemically, the granules of the tumor cells show autofluorescence and high activity of acid phosphatase, which was located electron-microscopically in the limiting membranes and matrices of the granules. It is suggested that the granular-cell tumor is a neoplasm of Schwann-cell origin with a unique metabolism that causes acceleration of autophagocytosis and accumulation of ceroidlipofuscin.", "contents": "Multiple granular-cell tumors of the ascending colon: microscopic study. Light and electron microscopic study of a case of multiple granular-cell tumor of the ascending colon is presented, and the relevant medical literature is reviewed. It seems that the biologic behavior of this tumor in the colon does not differ from that in other locations. Histologically, a few granular cells are seen in neural tissue in the vicinity of the tumor, suggesting a close relation of the tumor to the neural tissue. Electron-microscopically, the granular cells resemble Schwann cells more closely than neural cells and axons. Histochemically, the granules of the tumor cells show autofluorescence and high activity of acid phosphatase, which was located electron-microscopically in the limiting membranes and matrices of the granules. It is suggested that the granular-cell tumor is a neoplasm of Schwann-cell origin with a unique metabolism that causes acceleration of autophagocytosis and accumulation of ceroidlipofuscin."}
{"id": "PMID:212264", "title": "[Changes in 3H-noradrenaline activity in the adrenals and serum of rats under the influence of histamine and adrenocorticotropic hormone].", "content": "The authors examined the changes in the distribution of 3H-noradrenaline in the adrenal glands and serum of white rats-control and experimental-after administration of histamine and ACTH. The results from the experiments revealed characteristic curves of accumulation of 3H-noradrenaline in the adrenal glands of the examined animals, with maximum at the tenth minute and characteristic changes in the activity of the labeled noradrenaline in the adrenals and serum after administration of histamine and ACTH, followed up to the second hour. On the basis of the obtained results from the radiometric examination and from the follow-up of the level of the blood sugar, the authors make inferences for the sequence and character of the processes of incorporation and release of catecholamine from the adrenal glands under the action of ACTH and histamine.", "contents": "[Changes in 3H-noradrenaline activity in the adrenals and serum of rats under the influence of histamine and adrenocorticotropic hormone]. The authors examined the changes in the distribution of 3H-noradrenaline in the adrenal glands and serum of white rats-control and experimental-after administration of histamine and ACTH. The results from the experiments revealed characteristic curves of accumulation of 3H-noradrenaline in the adrenal glands of the examined animals, with maximum at the tenth minute and characteristic changes in the activity of the labeled noradrenaline in the adrenals and serum after administration of histamine and ACTH, followed up to the second hour. On the basis of the obtained results from the radiometric examination and from the follow-up of the level of the blood sugar, the authors make inferences for the sequence and character of the processes of incorporation and release of catecholamine from the adrenal glands under the action of ACTH and histamine."}
{"id": "PMID:212265", "title": "Cyanide-insensitive NADH oxidation by subcellular fractions isolated from human polymorphonuclear blood cells.", "content": "The biochemical triad, NADH oxidation, oxygen (O2) uptake and hydrogen peroxide (H2O2) formation, by subcellular fractions of human blood polymorphonuclears (PMNs) was investigated. It was found that this biochemical triad (1) was under the control of the granule-rich fraction (GRF) only; (2) was not inhibited by cyanide; (3) occurred stoichiometrically for its three components, and (4) accounted quantitatively for the respiratory burst of the stimulated PMN. It was also shown that the above biochemical triad (1) involved an enzymatic step; (2) was enhanced by acidic pH (0.5) and Mg++; (3) was inhibited by Cu++ or low concentration of Mn++; (4) was dependent on H2O2, perhydroxyl radical (HO2) and hydroxyl radical (HO) since either catalase or superoxide dismutase or scavengers of HO2 or HO were inhibitor, and (5) involved multistep reactions. Evidence is provided that the sequence of the reactions is first a generation of H2O2, (spontaneously from NADH in our incubation medium), secondly the production of HO from H2O2, thirdly the oxidation of NADH with further production of HO2,O2 uptake and H2O2 formation, probably through a chain reaction. The identification of the enzyme(s) involved in these multistep reactions needs further studies.", "contents": "Cyanide-insensitive NADH oxidation by subcellular fractions isolated from human polymorphonuclear blood cells. The biochemical triad, NADH oxidation, oxygen (O2) uptake and hydrogen peroxide (H2O2) formation, by subcellular fractions of human blood polymorphonuclears (PMNs) was investigated. It was found that this biochemical triad (1) was under the control of the granule-rich fraction (GRF) only; (2) was not inhibited by cyanide; (3) occurred stoichiometrically for its three components, and (4) accounted quantitatively for the respiratory burst of the stimulated PMN. It was also shown that the above biochemical triad (1) involved an enzymatic step; (2) was enhanced by acidic pH (0.5) and Mg++; (3) was inhibited by Cu++ or low concentration of Mn++; (4) was dependent on H2O2, perhydroxyl radical (HO2) and hydroxyl radical (HO) since either catalase or superoxide dismutase or scavengers of HO2 or HO were inhibitor, and (5) involved multistep reactions. Evidence is provided that the sequence of the reactions is first a generation of H2O2, (spontaneously from NADH in our incubation medium), secondly the production of HO from H2O2, thirdly the oxidation of NADH with further production of HO2,O2 uptake and H2O2 formation, probably through a chain reaction. The identification of the enzyme(s) involved in these multistep reactions needs further studies."}
{"id": "PMID:212266", "title": "Hysteretic nature of NADH substrate inhibition of bovine liver glutamate dehydrogenase.", "content": "NADH substrate inhibition of bovine liver glutamate dehydrogenase appears to be eliminated at enzyme concentrations above 0.5mg/ml. Since the inhibition cannot be restored by preincubation of the enzyme with any substrate or product combination, the release of inhibition had previously been considered the result of enzyme polymerization. Benzene-saturated solutions, however, increase the extent of enzyme polymerization without affecting the NADH inhibition. These and related control measurements demonstrate that the release of substrate inhibition is the result of a hysteretic transition of an enzyme central and transitory complex.", "contents": "Hysteretic nature of NADH substrate inhibition of bovine liver glutamate dehydrogenase. NADH substrate inhibition of bovine liver glutamate dehydrogenase appears to be eliminated at enzyme concentrations above 0.5mg/ml. Since the inhibition cannot be restored by preincubation of the enzyme with any substrate or product combination, the release of inhibition had previously been considered the result of enzyme polymerization. Benzene-saturated solutions, however, increase the extent of enzyme polymerization without affecting the NADH inhibition. These and related control measurements demonstrate that the release of substrate inhibition is the result of a hysteretic transition of an enzyme central and transitory complex."}
{"id": "PMID:212267", "title": "Molecular biology of metabolic disease: defects in the regulation of enzymic activity.", "content": "The Jacob-Monod model for the regulation of enzymic activity has been used in the analysis of some types of metabolic disease. Three lesions have been considered: (1) loss of allosteric inhibition of phosphofructokinase by citrate in the condition of lipomatosis; (2) failure of covalent modification of triglyceride lipase from inactive to active forms in the condition of triglyceride storage disease, and (3) failure of repression of HMG-CoA reductase by a mutant low-density liprotein in a new variant-of familial hypercholesterolaemia. Defects in enzymic regulation are contrasted with catalytic defects (the inborn errors); the major difference being an accumulation of a normal metabolic end-product of an unregulated pathway, rather than accumulation of an unusual intermediary metabolite as in the inborn errors.", "contents": "Molecular biology of metabolic disease: defects in the regulation of enzymic activity. The Jacob-Monod model for the regulation of enzymic activity has been used in the analysis of some types of metabolic disease. Three lesions have been considered: (1) loss of allosteric inhibition of phosphofructokinase by citrate in the condition of lipomatosis; (2) failure of covalent modification of triglyceride lipase from inactive to active forms in the condition of triglyceride storage disease, and (3) failure of repression of HMG-CoA reductase by a mutant low-density liprotein in a new variant-of familial hypercholesterolaemia. Defects in enzymic regulation are contrasted with catalytic defects (the inborn errors); the major difference being an accumulation of a normal metabolic end-product of an unregulated pathway, rather than accumulation of an unusual intermediary metabolite as in the inborn errors."}
{"id": "PMID:212269", "title": "Transient-phase studies on the arginine kinase reaction.", "content": "1. The initial formation of arginine phosphate by arginine kinase was studied in the time range 2.8--50 ms by the quenched-flow method. 2. A transient burst phase of product formation was obtained, the amplitude of which was temperature-dependent. At 35 degrees C it was 0.64 mol arginine phosphate/mol arginine kinase and at 12 degrees C, 0.25 mol/mol. 3. These results show that for the reaction pathway of arginine kinase the rate-limiting step follows the formation of arginine phosphate on the enzyme. This is in contrast to the creatine kinase reaction where no transient phase was observed [Engelborghs, Y., Marsh, A. & Gutfreund, H. (1975) Biochem. J. 151, 47--50]. 4. The rate-limiting step on the arginine kinase reaction pathway is only slightly affected by temperature: the change in Kcat with temperature is due to a change of an equilibrium constant pertaining to at least two previous steps.", "contents": "Transient-phase studies on the arginine kinase reaction. 1. The initial formation of arginine phosphate by arginine kinase was studied in the time range 2.8--50 ms by the quenched-flow method. 2. A transient burst phase of product formation was obtained, the amplitude of which was temperature-dependent. At 35 degrees C it was 0.64 mol arginine phosphate/mol arginine kinase and at 12 degrees C, 0.25 mol/mol. 3. These results show that for the reaction pathway of arginine kinase the rate-limiting step follows the formation of arginine phosphate on the enzyme. This is in contrast to the creatine kinase reaction where no transient phase was observed [Engelborghs, Y., Marsh, A. & Gutfreund, H. (1975) Biochem. J. 151, 47--50]. 4. The rate-limiting step on the arginine kinase reaction pathway is only slightly affected by temperature: the change in Kcat with temperature is due to a change of an equilibrium constant pertaining to at least two previous steps."}
{"id": "PMID:212270", "title": "Mitochondrial transport processes and oxidation of NADH by hypotonically-treated boar spermatozoa.", "content": "1. After hypotonic treatment spermatozoa have metabolic characteristics of mitochondria isolated from other cells. Ejaculated boar spermatozoa treated in this way can oxidise external NADH via both a lactate-pyruvate shuttle and a malate-aspartate cycle; this oxidation is coupled to the phosphorylation of ADP. 2. The dicarboxylate transport inhibitors butylmalonate, phenylsuccinate and bathophenanthroline sulphonate inhibit NADH oxidation dependent on added malate, glutamate and aspartate. alpha-Cyanocinnamate, a strong inhibitor of pyruvate transport, inhibits lactate-dependent NADH oxidation. 3. NADH oxidation dependent on malate, glutamate and aspartate is inhibited by uncoupling agents, but lactate-dependent NADH oxidation is stimulated. 4. Lactate-dependent NADH oxidation is inhibited by oxamate, an inhibitor of lactate dehydrogenase. Aminooxyacetate, an aminotransferase inhibitor, inhibits glutamate, malate and aspartate-dependent NADH oxidation. 5. Hypotonically-treated spermatozoa retain radioactivity after incubation with L-[U-14C]malate, [1,5-14C]citrate or [2-14C]malonate. Exchanges of retained radioactivity with various substrates indicate that dicarboxylate and tricarboxylate exchange carriers exist in the mitochondrial membrane.", "contents": "Mitochondrial transport processes and oxidation of NADH by hypotonically-treated boar spermatozoa. 1. After hypotonic treatment spermatozoa have metabolic characteristics of mitochondria isolated from other cells. Ejaculated boar spermatozoa treated in this way can oxidise external NADH via both a lactate-pyruvate shuttle and a malate-aspartate cycle; this oxidation is coupled to the phosphorylation of ADP. 2. The dicarboxylate transport inhibitors butylmalonate, phenylsuccinate and bathophenanthroline sulphonate inhibit NADH oxidation dependent on added malate, glutamate and aspartate. alpha-Cyanocinnamate, a strong inhibitor of pyruvate transport, inhibits lactate-dependent NADH oxidation. 3. NADH oxidation dependent on malate, glutamate and aspartate is inhibited by uncoupling agents, but lactate-dependent NADH oxidation is stimulated. 4. Lactate-dependent NADH oxidation is inhibited by oxamate, an inhibitor of lactate dehydrogenase. Aminooxyacetate, an aminotransferase inhibitor, inhibits glutamate, malate and aspartate-dependent NADH oxidation. 5. Hypotonically-treated spermatozoa retain radioactivity after incubation with L-[U-14C]malate, [1,5-14C]citrate or [2-14C]malonate. Exchanges of retained radioactivity with various substrates indicate that dicarboxylate and tricarboxylate exchange carriers exist in the mitochondrial membrane."}
{"id": "PMID:212271", "title": "Oxygen activation in isolated chloroplasts. Mechanism of ferredoxin-dependent ethylene formation from methionine.", "content": "Low-potential electron acceptors of photosystem I of chloroplast lamellae produce superoxide anions (0-2) and hydrogen peroxide by autoxidation, but have no effect on ethylene formation from methionine; equimolar amounts of ferredoxin are less active in photosynthetic O-2 and H2O2 production but strongly stimulate ethylene production from methionine. 2. Ten to fifty units of superoxide dismutase inhibit fifty to two hundred units of superoxide dismutase stimulate ethylene formation from methionine by chloroplast lamellae in the presence of ferredoxin. This stimulation is stronger at pH 7.0 than at pH 7.8. Catalase inhibits ethylene formation from methionine. 3. Pulse-radiolytic production of nitrite (NO-2) from hydroxylamine, initiated by hydroxyl radicals (.OH) or O-2, shows no difference in the presence or absence of ferredoxin, nor do the decay kinetics of O2. 4. From the above observations and from model reactions (xanthine/xanthine oxidase; iron salts in the presence of H2O2), it is concluded that reduced ferredoxin in the presence of H2O2 forms a Fenton-type oxidizing species for methionine, generating ethylene in the presence of pyridoxal phosphate. 5. Inhibitory effects of both superoxide dismutase and catalase in oxygen-dependent reactions need not necessarily indicate the participation of the 'Haber-Weiss' reaction.", "contents": "Oxygen activation in isolated chloroplasts. Mechanism of ferredoxin-dependent ethylene formation from methionine. Low-potential electron acceptors of photosystem I of chloroplast lamellae produce superoxide anions (0-2) and hydrogen peroxide by autoxidation, but have no effect on ethylene formation from methionine; equimolar amounts of ferredoxin are less active in photosynthetic O-2 and H2O2 production but strongly stimulate ethylene production from methionine. 2. Ten to fifty units of superoxide dismutase inhibit fifty to two hundred units of superoxide dismutase stimulate ethylene formation from methionine by chloroplast lamellae in the presence of ferredoxin. This stimulation is stronger at pH 7.0 than at pH 7.8. Catalase inhibits ethylene formation from methionine. 3. Pulse-radiolytic production of nitrite (NO-2) from hydroxylamine, initiated by hydroxyl radicals (.OH) or O-2, shows no difference in the presence or absence of ferredoxin, nor do the decay kinetics of O2. 4. From the above observations and from model reactions (xanthine/xanthine oxidase; iron salts in the presence of H2O2), it is concluded that reduced ferredoxin in the presence of H2O2 forms a Fenton-type oxidizing species for methionine, generating ethylene in the presence of pyridoxal phosphate. 5. Inhibitory effects of both superoxide dismutase and catalase in oxygen-dependent reactions need not necessarily indicate the participation of the 'Haber-Weiss' reaction."}
{"id": "PMID:212272", "title": "Collagenase sensitivity and aggregation properties of Electrophorus acetylcholinesterase.", "content": "Tailed forms of Electrophorus acetylcholinesterase, mainly A (9 S) and C (14.2 S) forms, have been subjected to collagenase treatment. Several steps have been identified, yielding molecules which have lost different portions of the tail, and eventually resulting in separation of the isolated tetramers. These modifications result in the disappearance of the low-ionic strength aggregating properties. The molecules which have retained relatively large fragments of the tail do not aggregate in the same conditions as the intact forms, but still form small aggregates in the presence of high levels of polyanions. A model of the tailed molecules, illustrating the existence of discrete collagenase-sensitive regions in the tail, is discussed.", "contents": "Collagenase sensitivity and aggregation properties of Electrophorus acetylcholinesterase. Tailed forms of Electrophorus acetylcholinesterase, mainly A (9 S) and C (14.2 S) forms, have been subjected to collagenase treatment. Several steps have been identified, yielding molecules which have lost different portions of the tail, and eventually resulting in separation of the isolated tetramers. These modifications result in the disappearance of the low-ionic strength aggregating properties. The molecules which have retained relatively large fragments of the tail do not aggregate in the same conditions as the intact forms, but still form small aggregates in the presence of high levels of polyanions. A model of the tailed molecules, illustrating the existence of discrete collagenase-sensitive regions in the tail, is discussed."}
{"id": "PMID:212273", "title": "Parathyroid hormone and calcitonin secretion in uraemic infants.", "content": "In six infants aged between 4 and 8 months with chronic renal failure, 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 under basal conditions and during an infusion of 20 mg/kg of 10% Ca gluconate in normal saline over 4 h. Under basal conditions four infants had normal serum Ca and P values, alkaline phosphatase levels at the upper limit of normal, and very high PTH (range: 1450--2550 pg Eq/ml) and CT (range: 700--1900 pg/ml) levels. The urinary Ca excretion was low, whereas the urinary excretion of P, hydroxyproline and cyclic AMP was high. During Ca infusion, the total serum Ca and CT levels increased, PTH fell without however reaching the normal upper limit, and urinary P and cyclic AMP excretion decreased. In two infants with osteodystrophy and the highest levels of PTH (2900 and 3500 pg Eq/ml respectively) there was no suppression of PTH during Ca infusion.", "contents": "Parathyroid hormone and calcitonin secretion in uraemic infants. In six infants aged between 4 and 8 months with chronic renal failure, 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 under basal conditions and during an infusion of 20 mg/kg of 10% Ca gluconate in normal saline over 4 h. Under basal conditions four infants had normal serum Ca and P values, alkaline phosphatase levels at the upper limit of normal, and very high PTH (range: 1450--2550 pg Eq/ml) and CT (range: 700--1900 pg/ml) levels. The urinary Ca excretion was low, whereas the urinary excretion of P, hydroxyproline and cyclic AMP was high. During Ca infusion, the total serum Ca and CT levels increased, PTH fell without however reaching the normal upper limit, and urinary P and cyclic AMP excretion decreased. In two infants with osteodystrophy and the highest levels of PTH (2900 and 3500 pg Eq/ml respectively) there was no suppression of PTH during Ca infusion."}
{"id": "PMID:212274", "title": "Influence of thyroid hormone on the positive inotropic effects mediated by alpha- and beta-adrenoceptors in isolated guinea pig atria and rabbit papillary muscles.", "content": "Effects of thyroxine treatment for 7--11 days on the positive inotropic effects mediated by alpha- and beta-adrenoceptors were studied in isolated guinea pig atria and rabbit papillary muscles. In guinea pig atria, the thyroxine treatment inhibited the positive inotropic effect of lower concentrations of phenylephrine (PHE), and attenuated the inhibitory effect of phentolamine on the PHE response. The effect of isoproterenol (ISO) was potentiated by the thyroxine treatment. In rabbit papillary muscles, the thyroxine treatment shifted the dose--response curve for PHE to the right and attenuated the inhibitory effect of phentolamine on the PHE response. Propranolol, in both guinea pig atria and rabbit papillary muscles, inhibited the PHE response more effectively in preparations from thyroxine-treated animals than in controls. In guinea peg atria, the attenuation of the PHE response mediated by alpha-adrenoceptors was observed after the thyroxine treatment for only 2 days, whereas the potentiation of the ISO response required the thyroxine treatment for a longer period. It was concluded that the thyroxine treatment attenuated the positive inotropic effect mediated by alpha-adrenoceptors and potentiated that mediated by beta-adrenoceptor-mediated positive inotropic effects due to the thyroxine treatment may be independent of each other.", "contents": "Influence of thyroid hormone on the positive inotropic effects mediated by alpha- and beta-adrenoceptors in isolated guinea pig atria and rabbit papillary muscles. Effects of thyroxine treatment for 7--11 days on the positive inotropic effects mediated by alpha- and beta-adrenoceptors were studied in isolated guinea pig atria and rabbit papillary muscles. In guinea pig atria, the thyroxine treatment inhibited the positive inotropic effect of lower concentrations of phenylephrine (PHE), and attenuated the inhibitory effect of phentolamine on the PHE response. The effect of isoproterenol (ISO) was potentiated by the thyroxine treatment. In rabbit papillary muscles, the thyroxine treatment shifted the dose--response curve for PHE to the right and attenuated the inhibitory effect of phentolamine on the PHE response. Propranolol, in both guinea pig atria and rabbit papillary muscles, inhibited the PHE response more effectively in preparations from thyroxine-treated animals than in controls. In guinea peg atria, the attenuation of the PHE response mediated by alpha-adrenoceptors was observed after the thyroxine treatment for only 2 days, whereas the potentiation of the ISO response required the thyroxine treatment for a longer period. It was concluded that the thyroxine treatment attenuated the positive inotropic effect mediated by alpha-adrenoceptors and potentiated that mediated by beta-adrenoceptor-mediated positive inotropic effects due to the thyroxine treatment may be independent of each other."}
{"id": "PMID:212275", "title": "Prednisolone-3,20-bisguanylhydrazone: the mode of interaction with rat brain sodium and potassium-activated adenosine triphosphatase.", "content": "The mechanism of interaction between prednisolone-3,20-bisguanylhydrazone (PBGH) and Na+,K+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) was studied using partially purified rat brain enzyme preparations. PBGH inhibited Na+,K+-ATPase rapidly and reversibly. The enzyme-inhibiting action of PBGH was competitively antagonized by potassium. PBGH inhibited Na+,Mg2+ and ATP-supported binding of (3H)-ouabain to the enzyme. When PBGH was added to the incubation mixture at the time when the (3H)-ouabain binding was close to its equilibrium state, the concentration of (3H)-ouabain complex was rapidly reduced and shifted to a lower equilibrium state. A double reciprocal plot analysis of the (3H)-ouabain binding data indicates that the inhibition of ouabain binding by PBGH is apparently competitive. Binding of (3H)-ouabain in the presence of Tris-phosphate and Mg2+ was also inhibited by unlabeled PBGH. Thus, it appears that the binding of PBGH precludes the binding of ouabain to Na+,K+-ATPase.", "contents": "Prednisolone-3,20-bisguanylhydrazone: the mode of interaction with rat brain sodium and potassium-activated adenosine triphosphatase. The mechanism of interaction between prednisolone-3,20-bisguanylhydrazone (PBGH) and Na+,K+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) was studied using partially purified rat brain enzyme preparations. PBGH inhibited Na+,K+-ATPase rapidly and reversibly. The enzyme-inhibiting action of PBGH was competitively antagonized by potassium. PBGH inhibited Na+,Mg2+ and ATP-supported binding of (3H)-ouabain to the enzyme. When PBGH was added to the incubation mixture at the time when the (3H)-ouabain binding was close to its equilibrium state, the concentration of (3H)-ouabain complex was rapidly reduced and shifted to a lower equilibrium state. A double reciprocal plot analysis of the (3H)-ouabain binding data indicates that the inhibition of ouabain binding by PBGH is apparently competitive. Binding of (3H)-ouabain in the presence of Tris-phosphate and Mg2+ was also inhibited by unlabeled PBGH. Thus, it appears that the binding of PBGH precludes the binding of ouabain to Na+,K+-ATPase."}
{"id": "PMID:212276", "title": "Hypotension induced by inhibition of angiotensin-converting enzyme in pentobarbital-anesthetized dogs.", "content": "The mechanism of the hypotensive response produced by inhibition of the angiotensin converting enzyme was studied in pentobarbital anesthetized dogs. A recently developed potent inhibitor of the converting enzyme, SQ 14,225 (D-3-mercapto-2-methyl propanoyl-L-proline), administered i.v. to intact dogs resulted in a rapid marked decrease in blood pressure. In nephrectomized dogs, SQ 14,225 retained significant hypotensive activity, although the absolute magnitude of the decreases in blood pressure were less than had been observed in dogs with intact kidneys. SQ 14,225 also lowered blood pressure when administered to intact dogs in which angiotensin II receptors had been blocked with the receptor antagonist Sar1,Ala8-angiotensin II. This apparent ability of SQ 14,225 to decrease blood pressure in the absence of a functional renin angiotensin system was shared by a structurally dissimilar, nonapeptide, angiotensin converting enzyme inhibitor, SQ 20,881 (Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro). SQ 20,881 also produced significant decreases in blood pressure in nephrectomized dogs. These findings indicate that the angiotensin converting enzyme inhibitors, SQ 14,225 and SQ 20,881 may lower blood pressure in anesthetized normotensive dogs via a mechanism unrelated to either the renin angiotensin system or the renal kinin system.", "contents": "Hypotension induced by inhibition of angiotensin-converting enzyme in pentobarbital-anesthetized dogs. The mechanism of the hypotensive response produced by inhibition of the angiotensin converting enzyme was studied in pentobarbital anesthetized dogs. A recently developed potent inhibitor of the converting enzyme, SQ 14,225 (D-3-mercapto-2-methyl propanoyl-L-proline), administered i.v. to intact dogs resulted in a rapid marked decrease in blood pressure. In nephrectomized dogs, SQ 14,225 retained significant hypotensive activity, although the absolute magnitude of the decreases in blood pressure were less than had been observed in dogs with intact kidneys. SQ 14,225 also lowered blood pressure when administered to intact dogs in which angiotensin II receptors had been blocked with the receptor antagonist Sar1,Ala8-angiotensin II. This apparent ability of SQ 14,225 to decrease blood pressure in the absence of a functional renin angiotensin system was shared by a structurally dissimilar, nonapeptide, angiotensin converting enzyme inhibitor, SQ 20,881 (Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro). SQ 20,881 also produced significant decreases in blood pressure in nephrectomized dogs. These findings indicate that the angiotensin converting enzyme inhibitors, SQ 14,225 and SQ 20,881 may lower blood pressure in anesthetized normotensive dogs via a mechanism unrelated to either the renin angiotensin system or the renal kinin system."}
{"id": "PMID:212277", "title": "Reserpine-induced supersensitivity to the inotropic and phosphorylase activating effects of glucagon in the perfused rat heart.", "content": "Glucagon (0.125--2.0 microgram) produced a dose-dependent increase in cyclic AMP, % phosphorylase a and force of contraction in the isolated perfused rat heart. Pretreatment of animals with reserpine (2.5 mg/kg, 24 h) resulted in an enhancement of the inotropic and phosphorylase activating effects of glucagon but the effect on cyclic AMP was not altered. It is suggested that reserpine-induced supersensitivity in the rat heart occurs at a point beyond the cyclic AMP step.", "contents": "Reserpine-induced supersensitivity to the inotropic and phosphorylase activating effects of glucagon in the perfused rat heart. Glucagon (0.125--2.0 microgram) produced a dose-dependent increase in cyclic AMP, % phosphorylase a and force of contraction in the isolated perfused rat heart. Pretreatment of animals with reserpine (2.5 mg/kg, 24 h) resulted in an enhancement of the inotropic and phosphorylase activating effects of glucagon but the effect on cyclic AMP was not altered. It is suggested that reserpine-induced supersensitivity in the rat heart occurs at a point beyond the cyclic AMP step."}
{"id": "PMID:212279", "title": "3H-Catecholamine binding to alpha-receptors in rat brain: enhancement by reserpine.", "content": "(+/-)-3H-Epinephrine and (-)-3H-norepinephrine bind to rat cortex membranes in a saturable manner with dissociation constants of 16.7 and 27 nM respectively. The maximum number of 3H-catecholamine binding sites, 10--12 pmoles/g tissue, and the pharmacological characteristics of (+/-)-3H-epinephrine binding, indicate that the catecholamines label the same alpha-noradrenergic receptor in the rat as does 3H-clonidine. At 25 degrees, (+/-)-3H-epinephrine binding associates rapidly to equilibrium, and dissociates in a biphasic manner. The affinities of alpha-agonists at the 3H-catecholamine binding site are 2--4 fold weaker in the rat than in the calf cortex under the same experimental conditions. Ergot alkaloids and phenoxybenzamine have similar affinities in the two tissues, whereas phentolamine and WB-4101 are 8--10 times weaker in the rat. Reserpine (0.25 mg/kg s.c. per day for 3 weeks) causes 25 and 46% increases in the numbers of (+/-)-3H-epinephrine and 3H-WB-4101 alpha-receptor binding sites respectively, and a 51% increase in the number of 3H-dihydroalprenolol beta-receptor sites, in rat forebrain. Reserpine pretreatment does not alter the affinities of either alpha- or beta-receptor 3H-ligands.", "contents": "3H-Catecholamine binding to alpha-receptors in rat brain: enhancement by reserpine. (+/-)-3H-Epinephrine and (-)-3H-norepinephrine bind to rat cortex membranes in a saturable manner with dissociation constants of 16.7 and 27 nM respectively. The maximum number of 3H-catecholamine binding sites, 10--12 pmoles/g tissue, and the pharmacological characteristics of (+/-)-3H-epinephrine binding, indicate that the catecholamines label the same alpha-noradrenergic receptor in the rat as does 3H-clonidine. At 25 degrees, (+/-)-3H-epinephrine binding associates rapidly to equilibrium, and dissociates in a biphasic manner. The affinities of alpha-agonists at the 3H-catecholamine binding site are 2--4 fold weaker in the rat than in the calf cortex under the same experimental conditions. Ergot alkaloids and phenoxybenzamine have similar affinities in the two tissues, whereas phentolamine and WB-4101 are 8--10 times weaker in the rat. Reserpine (0.25 mg/kg s.c. per day for 3 weeks) causes 25 and 46% increases in the numbers of (+/-)-3H-epinephrine and 3H-WB-4101 alpha-receptor binding sites respectively, and a 51% increase in the number of 3H-dihydroalprenolol beta-receptor sites, in rat forebrain. Reserpine pretreatment does not alter the affinities of either alpha- or beta-receptor 3H-ligands."}
{"id": "PMID:212283", "title": "Membrane-associated adenosine triphosphatase in normal and injured hypoglossal nuclei.", "content": "The hypoglossal nuclei of adult male albino rats, either normal, or from 1 to 70 days after left hypoglossal nerve transection, were studied cytochemically with a lead method for sodium- and potassium-activated membrane ATP-ase, using light and electron microscopy. Reaction product was measured at the light microscopical level by microdensitometry, and significance determined statistically. Light microscopy revealed a brown reaction product in the neuropil, but none in cell bodies. Blood vessel walls were more strongly coloured. Reaction product was undiminished by ouabain pre-incubation, or by incubation without sodium or potassium, or by incubation with calcium instead of magnesium. Reaction product was diminished by absence of magnesium if calcium was also absent, and abolished if sections were boiled before incubation, or if substrate was absent. Axotomy caused a statistically significant increase in neuropil reaction product in injured nuclei, maximal at 35 days postoperatively, and subsequently decreasing to normal at 70 days. Electron microscopy showed a predominantly surface membrane reaction product, with occasional positive intracellular cisternae. Basal lamina and intra-endothelial vacuoles were also positive. Axotomy resulted in the arrival and disappearance of microglis (2 to 35 days), followed by astrocyte hypertrophy (35 days), and increase in thickness and homogeneity of surface membrane reaction product. The results suggest the presence of one or more calcium- or magnesium-dependent membrane ATP-ases. The peak of the increase after axotomy is probably partly attributable to hypertrophic astrocytes, and partly to the surfaces of neuronal processes. Increase of membrane movements might explain such enzyme activity.", "contents": "Membrane-associated adenosine triphosphatase in normal and injured hypoglossal nuclei. The hypoglossal nuclei of adult male albino rats, either normal, or from 1 to 70 days after left hypoglossal nerve transection, were studied cytochemically with a lead method for sodium- and potassium-activated membrane ATP-ase, using light and electron microscopy. Reaction product was measured at the light microscopical level by microdensitometry, and significance determined statistically. Light microscopy revealed a brown reaction product in the neuropil, but none in cell bodies. Blood vessel walls were more strongly coloured. Reaction product was undiminished by ouabain pre-incubation, or by incubation without sodium or potassium, or by incubation with calcium instead of magnesium. Reaction product was diminished by absence of magnesium if calcium was also absent, and abolished if sections were boiled before incubation, or if substrate was absent. Axotomy caused a statistically significant increase in neuropil reaction product in injured nuclei, maximal at 35 days postoperatively, and subsequently decreasing to normal at 70 days. Electron microscopy showed a predominantly surface membrane reaction product, with occasional positive intracellular cisternae. Basal lamina and intra-endothelial vacuoles were also positive. Axotomy resulted in the arrival and disappearance of microglis (2 to 35 days), followed by astrocyte hypertrophy (35 days), and increase in thickness and homogeneity of surface membrane reaction product. The results suggest the presence of one or more calcium- or magnesium-dependent membrane ATP-ases. The peak of the increase after axotomy is probably partly attributable to hypertrophic astrocytes, and partly to the surfaces of neuronal processes. Increase of membrane movements might explain such enzyme activity."}
{"id": "PMID:212284", "title": "The ventral spino-olivocerebellar system in the cat. IV. Spinal transmission after administration of clonidine and L-dopa.", "content": "1. The transmission from the flexor reflex afferents (FRA) to the spino-olivocerebellar paths ascending through the ventral funiculus (VF-SOCPs; Oscarsson and Sj\u00f6lund, 1977) was compared with the transmission from the FRA to segmental reflex arcs in cats with the spinal cord transected in the third cervical segment sparing only the ventral funiculus on one side. The climbing fiber responses evoked in Purkinje cells by electrical stimulation of limb nerves were monitored by recording the mass activity at the cerebellar surface simultaneously from several termination zones, while the flexion reflex was recorded from a flexor nerve and the primary afferent depolarization (PAD) from a dorsal root filament. 2. Changes in the segmental reflex responses were produced by i.v. injections of l-Dopa and Clonidine. L-Dopa produced the expected depression of the flexion reflex and the FRA-induced PAD in the FRA, whereas Clonidine depressed only the flexion reflex but did not affect or even enhanced the FRA-induced PAD in the FRA. 3. The changes in transmission to one of the ascending paths, the a-VF-SOCP, parallelled that in the flexion reflex arc. The transmission to another path, the b2-VF-SOCP, parallelled that in the pathway responsible for the FRA-induced PAD in the FRA. 4. The remaining hindlimb paths, the c1- and c3-VF-SOCPs, monosynaptically activated from primary afferents, were little influenced by the changes induced in the segmental reflex arcs. 5. It is suggested that the a- and b2-VF-SOCPs carry information related to interneuronal activity in segmental centers, whereas the c1- and c3-VF-SOCPs forward information mainly related to peripheral events.", "contents": "The ventral spino-olivocerebellar system in the cat. IV. Spinal transmission after administration of clonidine and L-dopa. 1. The transmission from the flexor reflex afferents (FRA) to the spino-olivocerebellar paths ascending through the ventral funiculus (VF-SOCPs; Oscarsson and Sj\u00f6lund, 1977) was compared with the transmission from the FRA to segmental reflex arcs in cats with the spinal cord transected in the third cervical segment sparing only the ventral funiculus on one side. The climbing fiber responses evoked in Purkinje cells by electrical stimulation of limb nerves were monitored by recording the mass activity at the cerebellar surface simultaneously from several termination zones, while the flexion reflex was recorded from a flexor nerve and the primary afferent depolarization (PAD) from a dorsal root filament. 2. Changes in the segmental reflex responses were produced by i.v. injections of l-Dopa and Clonidine. L-Dopa produced the expected depression of the flexion reflex and the FRA-induced PAD in the FRA, whereas Clonidine depressed only the flexion reflex but did not affect or even enhanced the FRA-induced PAD in the FRA. 3. The changes in transmission to one of the ascending paths, the a-VF-SOCP, parallelled that in the flexion reflex arc. The transmission to another path, the b2-VF-SOCP, parallelled that in the pathway responsible for the FRA-induced PAD in the FRA. 4. The remaining hindlimb paths, the c1- and c3-VF-SOCPs, monosynaptically activated from primary afferents, were little influenced by the changes induced in the segmental reflex arcs. 5. It is suggested that the a- and b2-VF-SOCPs carry information related to interneuronal activity in segmental centers, whereas the c1- and c3-VF-SOCPs forward information mainly related to peripheral events."}
{"id": "PMID:212285", "title": "Conditioned changes of synaptic transmission in the motor cortex of the cat.", "content": "Intracellular recordings were made from 117 neurons in the motor cortex of anesthetized cats. The pyramidal tract (PT) and VL nucleus of thalamus were stimulated in order to activate the neurons from two directions. 1. PT cells were conditioned by antidromic trains (10--50 cps for 4--15 s) and by paired PT and VL stimuli with different intervals and sequences. The VL-EPSPs were examined before and after conditioning, to find differences in efficacy in giving rise to spikes. The conditioning procedures resulted in a remarkable facilitation of VL-EPSPs, manifesting itself as a significant rise of efficacy in generating spikes, a shortening of peak latency and in some cases, an enhancement of background firing. 2. In non-PT neurons the same conditioning procedures elicited heterosynaptic facilitation and a rise in firing activity. 3. Intracellularly injected square wave pulses also resulted in facilitation of VL-EPSPs. 4. Pairings of PT and VL stimuli were more effective than trains in evoking conditioned changes. 5. Plastic modifications were observed in the 13.7% of the neurons subjected to conditioning procedures. 6. The authors assume that synchronous activity of the pre- and postsynaptic neurons is a highly important condition for plastic changes in the efficacy of synaptic transmission.", "contents": "Conditioned changes of synaptic transmission in the motor cortex of the cat. Intracellular recordings were made from 117 neurons in the motor cortex of anesthetized cats. The pyramidal tract (PT) and VL nucleus of thalamus were stimulated in order to activate the neurons from two directions. 1. PT cells were conditioned by antidromic trains (10--50 cps for 4--15 s) and by paired PT and VL stimuli with different intervals and sequences. The VL-EPSPs were examined before and after conditioning, to find differences in efficacy in giving rise to spikes. The conditioning procedures resulted in a remarkable facilitation of VL-EPSPs, manifesting itself as a significant rise of efficacy in generating spikes, a shortening of peak latency and in some cases, an enhancement of background firing. 2. In non-PT neurons the same conditioning procedures elicited heterosynaptic facilitation and a rise in firing activity. 3. Intracellularly injected square wave pulses also resulted in facilitation of VL-EPSPs. 4. Pairings of PT and VL stimuli were more effective than trains in evoking conditioned changes. 5. Plastic modifications were observed in the 13.7% of the neurons subjected to conditioning procedures. 6. The authors assume that synchronous activity of the pre- and postsynaptic neurons is a highly important condition for plastic changes in the efficacy of synaptic transmission."}
{"id": "PMID:212286", "title": "The relationship of phosphodiesterase and cyclic AMP to the process of fluid secretion in the salivary glands of the ixodid tick Amblyomma americanum.", "content": "Phosphodiesterase (PDE) activity in the salivary glands of the female. Amblyomma americanum decreased as the tick progressed from a slow to a rapid phase of feeding, while the rate of fluid secretion increased when glands were stimulated with cyclic AMP and theophylline. Dopamine stimulated PDE activity and an 'inhibitory' factor was found in glands obtained from rapidly engorging ticks which decreased PDE activity. These findings are discussed as they relate to the process of fluid secretion by salivary glands of feeding ixodid ticks.", "contents": "The relationship of phosphodiesterase and cyclic AMP to the process of fluid secretion in the salivary glands of the ixodid tick Amblyomma americanum. Phosphodiesterase (PDE) activity in the salivary glands of the female. Amblyomma americanum decreased as the tick progressed from a slow to a rapid phase of feeding, while the rate of fluid secretion increased when glands were stimulated with cyclic AMP and theophylline. Dopamine stimulated PDE activity and an 'inhibitory' factor was found in glands obtained from rapidly engorging ticks which decreased PDE activity. These findings are discussed as they relate to the process of fluid secretion by salivary glands of feeding ixodid ticks."}
{"id": "PMID:212287", "title": "Lipoprotein lipase activator deficiency in very low density lipoproteins in rat nephrotic syndrome.", "content": "Marked urinary loss of lipoprotein lipase activator in experimental rat nephrotic syndrome may be partly responsible for its deficiency in plasma very low density lipoproteins.", "contents": "Lipoprotein lipase activator deficiency in very low density lipoproteins in rat nephrotic syndrome. Marked urinary loss of lipoprotein lipase activator in experimental rat nephrotic syndrome may be partly responsible for its deficiency in plasma very low density lipoproteins."}
{"id": "PMID:212288", "title": "Flavonoid compounds are potent inhibitors of cyclic AMP phosphodiesterase.", "content": "The inhibitory activity of 19 flavonoid molecules on cyclic AMP breakdown by a commercial beef heart phosphodiesterase preparation is reported. 7 compounds are active in the micromolar range, 2 of which have a potency equivalent to that of papaverine. Some structure activity relationships are drawn.", "contents": "Flavonoid compounds are potent inhibitors of cyclic AMP phosphodiesterase. The inhibitory activity of 19 flavonoid molecules on cyclic AMP breakdown by a commercial beef heart phosphodiesterase preparation is reported. 7 compounds are active in the micromolar range, 2 of which have a potency equivalent to that of papaverine. Some structure activity relationships are drawn."}
{"id": "PMID:212289", "title": "Relationship between A-type and C-type particles in Ehrlich ascites tumor cells.", "content": "Intracisternal and intracytoplasmic A-type particles were discovered in Ehrlich ascites tumor cells. In addition, 'mature' and 'immature' C-type particles were also seen in the intercellular space. It is believed that A particles may represent a precursor or a formative stage of the C particles.", "contents": "Relationship between A-type and C-type particles in Ehrlich ascites tumor cells. Intracisternal and intracytoplasmic A-type particles were discovered in Ehrlich ascites tumor cells. In addition, 'mature' and 'immature' C-type particles were also seen in the intercellular space. It is believed that A particles may represent a precursor or a formative stage of the C particles."}
{"id": "PMID:212290", "title": "The EM immunocytochemical demonstration of lysozyme in macrophage giant cells in sarcoidosis.", "content": "The giant cells (multinucleate macrophages) of human sarcoidosis have been shown by the unlabelled antibody immunoperoxidase technique at electron microscope level to contain lysozyme within cytoplasmic granules.", "contents": "The EM immunocytochemical demonstration of lysozyme in macrophage giant cells in sarcoidosis. The giant cells (multinucleate macrophages) of human sarcoidosis have been shown by the unlabelled antibody immunoperoxidase technique at electron microscope level to contain lysozyme within cytoplasmic granules."}
{"id": "PMID:212291", "title": "Biochemical studies of pigments from a pathogenic fungus Microsporum cookei. V. Evidence for the transmembrane permeability of xanthomegnin across phospholipid bilayer membranes.", "content": "Direct evidence is provided for the transmembrane permeation of xanthomegnin across phospholipid bilayer membranes using ascorbate-loaded liposomes. This process may be associated with an uncoupling effect on the oxidative phosphorylation of mitochondria.", "contents": "Biochemical studies of pigments from a pathogenic fungus Microsporum cookei. V. Evidence for the transmembrane permeability of xanthomegnin across phospholipid bilayer membranes. Direct evidence is provided for the transmembrane permeation of xanthomegnin across phospholipid bilayer membranes using ascorbate-loaded liposomes. This process may be associated with an uncoupling effect on the oxidative phosphorylation of mitochondria."}
{"id": "PMID:212292", "title": "Inhibition of phosphodiesterase activity of human spermatozoa by spermine.", "content": "Sperm motility and metabolism are dependent upon the levels of cyclic AMP. Our studies have demonstrated that spermine by inhibiting sperm phosphodiesterase activity could regulate sperm physiology.", "contents": "Inhibition of phosphodiesterase activity of human spermatozoa by spermine. Sperm motility and metabolism are dependent upon the levels of cyclic AMP. Our studies have demonstrated that spermine by inhibiting sperm phosphodiesterase activity could regulate sperm physiology."}
{"id": "PMID:212293", "title": "[Effect of nicotinamide, adenosine and nicotinamide-adenine dinucleotide on the NAD and NAD.H2 content in the liver and brain of intact rats and in hypoxia].", "content": "Nicotine-amide (25 mg/kg) in the liver and adenosine (50 mg/kg) in the liver and brain of intact rats enhance the NAD+NAD'H2 content. These drugs when used in the same doses raise the NAD+NAD'H2 level in the organs reduced in hypoxia and their proportion only with the combined application of these drugs. NAD (30 mg/kg) increases the NAD+NAD'H2 concentration in the liver and brain of intact and in the liver of \"hypoxic\" rats. It appears that in the mechanism of the antihypoxic action of nicotine-amide, adenozine and NAD a definite part plays their action on the level of nicotine-amide co-enzymes.", "contents": "[Effect of nicotinamide, adenosine and nicotinamide-adenine dinucleotide on the NAD and NAD.H2 content in the liver and brain of intact rats and in hypoxia]. Nicotine-amide (25 mg/kg) in the liver and adenosine (50 mg/kg) in the liver and brain of intact rats enhance the NAD+NAD'H2 content. These drugs when used in the same doses raise the NAD+NAD'H2 level in the organs reduced in hypoxia and their proportion only with the combined application of these drugs. NAD (30 mg/kg) increases the NAD+NAD'H2 concentration in the liver and brain of intact and in the liver of \"hypoxic\" rats. It appears that in the mechanism of the antihypoxic action of nicotine-amide, adenozine and NAD a definite part plays their action on the level of nicotine-amide co-enzymes."}
{"id": "PMID:212320", "title": "Chemical grafting of functional NAD in the active site of a dehydrogenase: regeneration in situ.", "content": "A functional NAD molecule was immobilized at the active site of Alcohol dehydrogenase within a proteic membrane. The presence and the functionality of the cofactor was checked by fluorescence analysis. The dehydrogenase NAD membrane does not require addition of soluble cofactor for its activity. The system represents a new worthwhile approach because both problems of retention and regeneration of cofactor are solved. The method can be used not only for industrial and analytical applications but also to try to get a better understanding of the kinetics and mechanisms of the catalytic action of dehydrogenase.", "contents": "Chemical grafting of functional NAD in the active site of a dehydrogenase: regeneration in situ. A functional NAD molecule was immobilized at the active site of Alcohol dehydrogenase within a proteic membrane. The presence and the functionality of the cofactor was checked by fluorescence analysis. The dehydrogenase NAD membrane does not require addition of soluble cofactor for its activity. The system represents a new worthwhile approach because both problems of retention and regeneration of cofactor are solved. The method can be used not only for industrial and analytical applications but also to try to get a better understanding of the kinetics and mechanisms of the catalytic action of dehydrogenase."}
{"id": "PMID:212325", "title": "The photobiogenesis and metabolism of vitamin D.", "content": "Provitamin D3 (7-dehydrocholesterol) is converted to previtamin D3 by the action of ultraviolet radiation on the skin. Previtamin D3 thermally isomerizes to vitamin D3 in the skin and the vitamin is then transported to the liver on the vitamin D-binding protein. Although there are extrahepatic vitamin D-25-hydroxylases, the liver is the major site for the 25-hydroxylation of vitamin D. In response to hypocalcemia and hypophosphatemia, 25-OH-D is metabolized by a renal-cytochrome. P450-dependent mixed function oxidase system is 1alpha,25(OH)2D. When calcium and phosphate homeostasis prevails the renal 25-OH-D-1alpha-hydroxylase activity is limited and instead a non-cytochrome P450 mixed function oxidase metabolizes 25-OH-D to 24R,25(OH)2D. Parathyroid hormone has clearly been shown to be a trophin for the renal synthesis of 1,25(OH)2D; however, the role and significance of the adrenal steroids, or gonadal and pituitary hormones, on the renal 25-OH-D-1alpha-hydroxylase is not well defined. The regulation of the photometabolism of provitamin D3 to vitamin D3, the role and significance of the side-chain metabolism of 1,25(OH)2D by the small intestine, and the metabolism of 25-OH-D to 24R,25(OH)2D by chondrocytes and its stimulation of protein synthesis in these cells are just a few issues that will require further investigation.", "contents": "The photobiogenesis and metabolism of vitamin D. Provitamin D3 (7-dehydrocholesterol) is converted to previtamin D3 by the action of ultraviolet radiation on the skin. Previtamin D3 thermally isomerizes to vitamin D3 in the skin and the vitamin is then transported to the liver on the vitamin D-binding protein. Although there are extrahepatic vitamin D-25-hydroxylases, the liver is the major site for the 25-hydroxylation of vitamin D. In response to hypocalcemia and hypophosphatemia, 25-OH-D is metabolized by a renal-cytochrome. P450-dependent mixed function oxidase system is 1alpha,25(OH)2D. When calcium and phosphate homeostasis prevails the renal 25-OH-D-1alpha-hydroxylase activity is limited and instead a non-cytochrome P450 mixed function oxidase metabolizes 25-OH-D to 24R,25(OH)2D. Parathyroid hormone has clearly been shown to be a trophin for the renal synthesis of 1,25(OH)2D; however, the role and significance of the adrenal steroids, or gonadal and pituitary hormones, on the renal 25-OH-D-1alpha-hydroxylase is not well defined. The regulation of the photometabolism of provitamin D3 to vitamin D3, the role and significance of the side-chain metabolism of 1,25(OH)2D by the small intestine, and the metabolism of 25-OH-D to 24R,25(OH)2D by chondrocytes and its stimulation of protein synthesis in these cells are just a few issues that will require further investigation."}
{"id": "PMID:212326", "title": "Foodborne hazards of microbial origin.", "content": "Foods can serve as vehicles of many pathogenic and toxigenic agents of disease. Bacterial agents comprise three groups: 1) those that grow in the food and produce an active toxin before consumption (e.g., clostridium botulinium); 2) those that merely exist as contaminants in the food but are able to initiate infection when swallowed (e.g., Salmonella spp.); and 3) those that multiply and produce large numbers of vegetative cells in the food, then release an active enterotoxin when they sporulate in the gut. A few parasitic (e.g., Trichinella spiralis) and viral agents (e.g., hepatitis A) also can be transmitted by food. Botulinum poisoning is the deadliest foodborne disease. The potential danger of botulism from cured meats is a major factor in the argument over use of nitrites as meat curing agents. A new disease called infant botulism has been recognized since 1976. Apparently it is not foodborne but results from intraintestinal growth of C. botulinum in very young infants. Salmonellosis is the most important of the foodborne diseases from the standpoint of overall human health. The primary vehicles are contaminated raw meat, poultry, and eggs. Faulty food handling practices are responsible for most food poisoning in the United States.", "contents": "Foodborne hazards of microbial origin. Foods can serve as vehicles of many pathogenic and toxigenic agents of disease. Bacterial agents comprise three groups: 1) those that grow in the food and produce an active toxin before consumption (e.g., clostridium botulinium); 2) those that merely exist as contaminants in the food but are able to initiate infection when swallowed (e.g., Salmonella spp.); and 3) those that multiply and produce large numbers of vegetative cells in the food, then release an active enterotoxin when they sporulate in the gut. A few parasitic (e.g., Trichinella spiralis) and viral agents (e.g., hepatitis A) also can be transmitted by food. Botulinum poisoning is the deadliest foodborne disease. The potential danger of botulism from cured meats is a major factor in the argument over use of nitrites as meat curing agents. A new disease called infant botulism has been recognized since 1976. Apparently it is not foodborne but results from intraintestinal growth of C. botulinum in very young infants. Salmonellosis is the most important of the foodborne diseases from the standpoint of overall human health. The primary vehicles are contaminated raw meat, poultry, and eggs. Faulty food handling practices are responsible for most food poisoning in the United States."}
{"id": "PMID:212327", "title": "Acetylcholine-induced ionic channels in rat skeletal muscle.", "content": "This paper briefly reviews the evidence for ionic channels mediating the conductance increase caused by acetylcholine application to the end-plate of skeletal muscle fibers. \"Membrane noise\" observed during application of constant low concentrations of acetylcholine to an end-plate is thought to arise from the random superposition of many elementary events corresponding to the opening and closing of discrete ion channels. Statistical analysis of acetylcholine-induced noise reveals an elementary conductance event of of 34 pS (1 S = 1 omega-1) amplitude and 1 msec duration at room temperature in rat muscle fibers. Both size and duration of the elementary event are temperature dependent. Analysis of currents induced by application of acetylcholine to the extrasynaptic membrane of chronically denervated fibers shows that the elementary conductance has a similar size but is of much longer duration. Direct recording of square pulse-like currents by a patch clamp method confirms some of the conclusions drawn from fluctuation analysis.", "contents": "Acetylcholine-induced ionic channels in rat skeletal muscle. This paper briefly reviews the evidence for ionic channels mediating the conductance increase caused by acetylcholine application to the end-plate of skeletal muscle fibers. \"Membrane noise\" observed during application of constant low concentrations of acetylcholine to an end-plate is thought to arise from the random superposition of many elementary events corresponding to the opening and closing of discrete ion channels. Statistical analysis of acetylcholine-induced noise reveals an elementary conductance event of of 34 pS (1 S = 1 omega-1) amplitude and 1 msec duration at room temperature in rat muscle fibers. Both size and duration of the elementary event are temperature dependent. Analysis of currents induced by application of acetylcholine to the extrasynaptic membrane of chronically denervated fibers shows that the elementary conductance has a similar size but is of much longer duration. Direct recording of square pulse-like currents by a patch clamp method confirms some of the conclusions drawn from fluctuation analysis."}
{"id": "PMID:212330", "title": "Large-scale production, concentration and purification of Rous Sarcoma Virus in tissue culture.", "content": "A method is described for long-term standard production of purified virus from cultures of PR-RSV-C-transformed chicken cells. The mean yields were 4.91 mg of purified virus per liter of culture medium. Cells were grown in long-term cultures for 26 weeks. A combination of polyethylene glycol 6 000 precipitation and zonal centrifugation has been found satisfactory for virus concentration and purification.", "contents": "Large-scale production, concentration and purification of Rous Sarcoma Virus in tissue culture. A method is described for long-term standard production of purified virus from cultures of PR-RSV-C-transformed chicken cells. The mean yields were 4.91 mg of purified virus per liter of culture medium. Cells were grown in long-term cultures for 26 weeks. A combination of polyethylene glycol 6 000 precipitation and zonal centrifugation has been found satisfactory for virus concentration and purification."}
{"id": "PMID:212331", "title": "Fractionation of proteins from Rous sarcoma virus and avian myeloblastosis virus by isoelectric focusing.", "content": "The isoelectric focusing technique in the pH gradients was used for a preparative isolation of proteins from Rous sarcoma virus and avian myeloblastosis virus. The purified major gs protein, p27 (pI = 9.1) and the gP86 (pI = 5.3) were obtained after disruption of virus with 1% non-ionogenic detergent in the presence of 6M urea. The p10, p15, and p19 were present in the same range of pH (pI = 6.8). A strongly basic protein, immunologically active, presumably the p12, was found in the alkaline region of the pH gradient 10.8. These proteins fully retained their immunological activity. On the other hand, in the acidic region of the pH gradient between pH 4 and 5, strong precipitates were regularly found. These precipitates were complexes which were formed by interaction of the acid components of ampholines with the viral proteins during isoelectric focusing. Almost all viral proteins were present, differing only in quantity. The complexes were stabile in 1% non-inogenic detergent and 6M urea. They were dissociated with 1% SDS and 5M urea, and had no immunological activity. The methods of virus disruption and possibilities of formation of the ampholine-viral protein complexes are discussed.", "contents": "Fractionation of proteins from Rous sarcoma virus and avian myeloblastosis virus by isoelectric focusing. The isoelectric focusing technique in the pH gradients was used for a preparative isolation of proteins from Rous sarcoma virus and avian myeloblastosis virus. The purified major gs protein, p27 (pI = 9.1) and the gP86 (pI = 5.3) were obtained after disruption of virus with 1% non-ionogenic detergent in the presence of 6M urea. The p10, p15, and p19 were present in the same range of pH (pI = 6.8). A strongly basic protein, immunologically active, presumably the p12, was found in the alkaline region of the pH gradient 10.8. These proteins fully retained their immunological activity. On the other hand, in the acidic region of the pH gradient between pH 4 and 5, strong precipitates were regularly found. These precipitates were complexes which were formed by interaction of the acid components of ampholines with the viral proteins during isoelectric focusing. Almost all viral proteins were present, differing only in quantity. The complexes were stabile in 1% non-inogenic detergent and 6M urea. They were dissociated with 1% SDS and 5M urea, and had no immunological activity. The methods of virus disruption and possibilities of formation of the ampholine-viral protein complexes are discussed."}
{"id": "PMID:212332", "title": "Long-term karyological study of RVP3 tumour cells grown in vitro.", "content": "The RVP3 cell line established from an in vivo passaged RVP3 tumour, which originally arose in RSV-injected mice, was analyzed at different passage levels and characterized virologically and cytogenetically. The RVP3 cell line is characterized by the presence of 2 to 5 medium-sized to large metacentric chromosomes, the majority of the mitoses contain about 1 subtelocentric chromosome, and in addition, every mitosis contains several chromosomal structures corresponding to the group called m-ms that comprises both minute chromatin bodies and microchromosomes. In three monocellular clones derived from the RVP3 cell line with a similar karyological picture it was established that the number of m-ms increased proportionally to the total number of chromosomes in individual metaphases. It was verified that: the RVP3 cell population does not contain any transmissible agent producing chromosomal changes in mouse cells; RVP3 cells are highly malignant; no RSV could be rescued from the clone tested. The significance of m-ms is discussed.", "contents": "Long-term karyological study of RVP3 tumour cells grown in vitro. The RVP3 cell line established from an in vivo passaged RVP3 tumour, which originally arose in RSV-injected mice, was analyzed at different passage levels and characterized virologically and cytogenetically. The RVP3 cell line is characterized by the presence of 2 to 5 medium-sized to large metacentric chromosomes, the majority of the mitoses contain about 1 subtelocentric chromosome, and in addition, every mitosis contains several chromosomal structures corresponding to the group called m-ms that comprises both minute chromatin bodies and microchromosomes. In three monocellular clones derived from the RVP3 cell line with a similar karyological picture it was established that the number of m-ms increased proportionally to the total number of chromosomes in individual metaphases. It was verified that: the RVP3 cell population does not contain any transmissible agent producing chromosomal changes in mouse cells; RVP3 cells are highly malignant; no RSV could be rescued from the clone tested. The significance of m-ms is discussed."}
{"id": "PMID:212335", "title": "Effects of phosphoenolpyruvate, other glycolytic intermediates and methylxanthines on calcium uptake by a mitochondrial fraction from rat pancreatic islets.", "content": "45Ca2+-accumulation by a mitochondrial fraction from isolated rat pancreatic islets was stronly stimulated by ATP. The ATP-dependent uptake was inhibited by phosphoenolpyruvate in a dose-dependent manner over a wide variety of conditions. Inhibition by phosphoenolpyruvate was non-completitive with respect to calcium, competitive with respect to magnesium, and antagonised by high Mg-ATP2- concentrations; fructose 1,6-diphosphate also decreased 45Ca2+-uptake. Other glucose metabolites were either less effective or ineffective in diminishing mitochondrial 45Ca2+-accumulation. The ATP-dependent uptake was also inhibited by xanthine derivatives (caffeine and 3-isobutyl-1-methylaxanthine) which potentiate the effects of glucose on insulin secretion. Cyclic AMP had no effect. It is thought that the rate of insulin secretion is a function of the cytosolic calcium concentration in the B-cell. These data show that phosphoenolpyruvate, fructose 1,6-diphosphate and methylxanthines might influence exocytosis by direct effects on mitochondrial calcium accumulation, and thus the intracellular distribution of calcium.", "contents": "Effects of phosphoenolpyruvate, other glycolytic intermediates and methylxanthines on calcium uptake by a mitochondrial fraction from rat pancreatic islets. 45Ca2+-accumulation by a mitochondrial fraction from isolated rat pancreatic islets was stronly stimulated by ATP. The ATP-dependent uptake was inhibited by phosphoenolpyruvate in a dose-dependent manner over a wide variety of conditions. Inhibition by phosphoenolpyruvate was non-completitive with respect to calcium, competitive with respect to magnesium, and antagonised by high Mg-ATP2- concentrations; fructose 1,6-diphosphate also decreased 45Ca2+-uptake. Other glucose metabolites were either less effective or ineffective in diminishing mitochondrial 45Ca2+-accumulation. The ATP-dependent uptake was also inhibited by xanthine derivatives (caffeine and 3-isobutyl-1-methylaxanthine) which potentiate the effects of glucose on insulin secretion. Cyclic AMP had no effect. It is thought that the rate of insulin secretion is a function of the cytosolic calcium concentration in the B-cell. These data show that phosphoenolpyruvate, fructose 1,6-diphosphate and methylxanthines might influence exocytosis by direct effects on mitochondrial calcium accumulation, and thus the intracellular distribution of calcium."}
{"id": "PMID:212336", "title": "86Rb+ fluxes and K+-stimulated nitrophenyl phosphatase activity in the pancreatic islets of genetically diabetic mice (C57BL/KsJ-db/db).", "content": "Fluxes of 86Rb+ and hydrolysis of p-nitrophenyl phosphate were measured in collagenase-isolated islets of diabetic C57BL/KsJ-db/db-mice and normal controls (C57BL/KsJ-+/+). Both types of islets accumulated Rb+ avidly, as originally reported for hand-dissected islets of non-inbred ob/ob-mice. KsJ-db/db-mouse islets showed enhanced accumulation of Rb+ and normal activity of K+-activated nitrophenyl phosphatase. D-glucose, 20 mmol/l, inhibited Rb+ efflux in normal islets but not in those from KsJ-db/db-mice. The glucose insensitivity of Rb+ efflux was observed in young animals, which exhibit glucose-induced insulin release, as well as in old animals, which do not secrete insulin in response to glucose. The anomalous regulation of Rb+ efflux already present in young animals may bear on the liability of KsJ-db/db-mouse B-cells to develop defective control of membrane potential, an abnormal metabolism of cyclic AMP, and a marked failure of insulin secretory capacity.", "contents": "86Rb+ fluxes and K+-stimulated nitrophenyl phosphatase activity in the pancreatic islets of genetically diabetic mice (C57BL/KsJ-db/db). Fluxes of 86Rb+ and hydrolysis of p-nitrophenyl phosphate were measured in collagenase-isolated islets of diabetic C57BL/KsJ-db/db-mice and normal controls (C57BL/KsJ-+/+). Both types of islets accumulated Rb+ avidly, as originally reported for hand-dissected islets of non-inbred ob/ob-mice. KsJ-db/db-mouse islets showed enhanced accumulation of Rb+ and normal activity of K+-activated nitrophenyl phosphatase. D-glucose, 20 mmol/l, inhibited Rb+ efflux in normal islets but not in those from KsJ-db/db-mice. The glucose insensitivity of Rb+ efflux was observed in young animals, which exhibit glucose-induced insulin release, as well as in old animals, which do not secrete insulin in response to glucose. The anomalous regulation of Rb+ efflux already present in young animals may bear on the liability of KsJ-db/db-mouse B-cells to develop defective control of membrane potential, an abnormal metabolism of cyclic AMP, and a marked failure of insulin secretory capacity."}
{"id": "PMID:212337", "title": "The ultrastructure of functional mouse adrenal cortical tumor cells in vitro.", "content": "Cells derived from a transplantable mouse adrenal cortical tumor maintain their differentiated function in vitro and secrete steroids in response to ACTH and other stimulatory agents. The cell line has been widely employed for various biochemical investigations but there have been few attempts to correlate this work with morphologic data. This communication describes the electron microscopic appearance of the tumor transplant in vivo and primary cultures derived from it at various intervals after the cells are placed in culture. Tumor cells in vivo bear considerable resemblance to normal adult mouse adrenal cortical cells. Organelles generally considered to be directly involved in steroid biosynthesis (mitochondria, smooth endoplasmic reticulum and lipid droplets) are not drastically altered. Certain modifications of the vasculature and cell membrane, seemingly related to steroidogenesis, are present in both the tumor and normal adrenal cortex. Within 2 days after the tumor cells are introduced to culture, their cytoplasm assumes a more simplified appearance. Smooth endoplasmic reticulum is less conspicuous and free ribosomes and polysomes are very abundant. Mitchondrial inner membranes are reorganized from a saccular arrangement in the cells in vivo into distinct lamellar cristae. The tumor cells now resemble undifferentiated embryonic adrenal cells, or cultured adrenal cells from various mammalian sources which have dedifferentiated in the absence of ACTH. In their morphologically unspecialized state, the normal cells are incapable of functional responses to ACTH. In contrast, the cultured, dedifferentiated tumor cells respond within minutes to this hormone and can demonstrate 5-20 fold increases in their basal steroid output. These data suggest that substantial steroidogenic activity can occur although the characteristic appearance of adrenal mitochondria is absent.", "contents": "The ultrastructure of functional mouse adrenal cortical tumor cells in vitro. Cells derived from a transplantable mouse adrenal cortical tumor maintain their differentiated function in vitro and secrete steroids in response to ACTH and other stimulatory agents. The cell line has been widely employed for various biochemical investigations but there have been few attempts to correlate this work with morphologic data. This communication describes the electron microscopic appearance of the tumor transplant in vivo and primary cultures derived from it at various intervals after the cells are placed in culture. Tumor cells in vivo bear considerable resemblance to normal adult mouse adrenal cortical cells. Organelles generally considered to be directly involved in steroid biosynthesis (mitochondria, smooth endoplasmic reticulum and lipid droplets) are not drastically altered. Certain modifications of the vasculature and cell membrane, seemingly related to steroidogenesis, are present in both the tumor and normal adrenal cortex. Within 2 days after the tumor cells are introduced to culture, their cytoplasm assumes a more simplified appearance. Smooth endoplasmic reticulum is less conspicuous and free ribosomes and polysomes are very abundant. Mitchondrial inner membranes are reorganized from a saccular arrangement in the cells in vivo into distinct lamellar cristae. The tumor cells now resemble undifferentiated embryonic adrenal cells, or cultured adrenal cells from various mammalian sources which have dedifferentiated in the absence of ACTH. In their morphologically unspecialized state, the normal cells are incapable of functional responses to ACTH. In contrast, the cultured, dedifferentiated tumor cells respond within minutes to this hormone and can demonstrate 5-20 fold increases in their basal steroid output. These data suggest that substantial steroidogenic activity can occur although the characteristic appearance of adrenal mitochondria is absent."}
{"id": "PMID:212338", "title": "Ultrasound guided fine-needle aspiration biopsy of abdominal masses.", "content": "Twenty-six cases of ultrasonically guided percutaneous fine-needle aspiration biopsies of abdominal masses are reported. Included are masses in the pancreas, retroperitoneum, liver, kidney, and pelvis. Aspiration biopsies accurately diagnosed or excluded malignancy in 21 patients (81%). The procedure, performed under local anesthesia, is rapid, simple and almost painless. No complications occurred; specifically, there was no hemorrhage, peritonitis, or spread of tumor along the needle tract.", "contents": "Ultrasound guided fine-needle aspiration biopsy of abdominal masses. Twenty-six cases of ultrasonically guided percutaneous fine-needle aspiration biopsies of abdominal masses are reported. Included are masses in the pancreas, retroperitoneum, liver, kidney, and pelvis. Aspiration biopsies accurately diagnosed or excluded malignancy in 21 patients (81%). The procedure, performed under local anesthesia, is rapid, simple and almost painless. No complications occurred; specifically, there was no hemorrhage, peritonitis, or spread of tumor along the needle tract."}
{"id": "PMID:212339", "title": "Multiple concentric ring sign in the ultrasonographic diagnosis of intussusception.", "content": "Gray scale ultrasound examination of two patients with abdominal space-occupying lesions demonstrated characteristic ring shadows on longitudinal scans. In one case a multiple concentric ring shadow resulted from an ileocolic intussusception, and in the other a \"bull's eye\" image was due to an infiltrating carcinoma of the pyloric antrum. A study of these patients confirms the suspicion [1] that there is a characteristic ultrasonic appearance of intussusception in bowel loops.", "contents": "Multiple concentric ring sign in the ultrasonographic diagnosis of intussusception. Gray scale ultrasound examination of two patients with abdominal space-occupying lesions demonstrated characteristic ring shadows on longitudinal scans. In one case a multiple concentric ring shadow resulted from an ileocolic intussusception, and in the other a \"bull's eye\" image was due to an infiltrating carcinoma of the pyloric antrum. A study of these patients confirms the suspicion [1] that there is a characteristic ultrasonic appearance of intussusception in bowel loops."}
{"id": "PMID:212340", "title": "ERCP update: diagnostic and therapeutic applications.", "content": "Endoscopic retograde cholangiopancreatography (ERCP) is currently utilized to evaluate jaundice, both intra- and extrahepatic, and can differentiate between these by demonstrating specific anatomic lesions. ERCP is definitive in the evaluation of gallbladder disease when other modalities are indefinite. For the first time outside the operating room, the pancreatic duct can be opacified by ERCP. The newest application of ERCP, endoscopic papillotomy (EP), has revolutionized the treatment of common bile duct gallstones and stenosis of the duct, offering a safe and effective alternative to repeated surgery, especially in those patients at risk. Because of these diverse and effective applications, ERCP has become firmly established in our diagnostic armamentarium.", "contents": "ERCP update: diagnostic and therapeutic applications. Endoscopic retograde cholangiopancreatography (ERCP) is currently utilized to evaluate jaundice, both intra- and extrahepatic, and can differentiate between these by demonstrating specific anatomic lesions. ERCP is definitive in the evaluation of gallbladder disease when other modalities are indefinite. For the first time outside the operating room, the pancreatic duct can be opacified by ERCP. The newest application of ERCP, endoscopic papillotomy (EP), has revolutionized the treatment of common bile duct gallstones and stenosis of the duct, offering a safe and effective alternative to repeated surgery, especially in those patients at risk. Because of these diverse and effective applications, ERCP has become firmly established in our diagnostic armamentarium."}
{"id": "PMID:212341", "title": "Cyclic nucleotide-dependent protein kinase activity in acinar cells from guinea pig pancreas.", "content": "Acinar cells from guinea pig pancreas possess two distinct protein kinase activities. Cyclic GMP-dependent kinase elutes as a single peak on diethylaminoethyl (DEAE)- cellulose chromatography, is not inhibited by protein kinase inhibitor, and has a greater affinity for cyclic GMP (half-maximal activation at 20 nM) than for cyclic AMP (half-maximal activation at 100 nM). Cyclic AMP-dependent kinase elutes as two peaks on DEAE-cellulose chromatography, is inhibited by protein kinase inhibitor, and has a greater affinity for cyclic AMP (half-maximal activation at 20 nM) than for cyclic GMP (half-maximal activation at 7 micrometer). Binding of cyclic 3H-nucleotides to the enzyme preparation was rapid, specific, temperature-dependent, and reversible, and there was a close correlation between the ability of a particular cyclic nucleotide to inhibit binding of cyclic 3H-nucleotide and its ability of a particular cyclic nucleotide to inhibit binding of cyclic H-nucleotide and its ability to activate protein kinase. Binding of cyclic 3H--nucleotide could not be described as a simple bimolecular reaction and native cyclic nucleotides accelerated the dissociation of bound, labeled cyclic nucleotide. Vasoactive intestinal peptide or secretin, each of which increases cellular cyclic AMP, caused endogenous activation of protein kinase and inhibition of cyclic [3H]AMP binding but did not alter bindings of cyclic [3H]GMP or cyclic [3H]AMP.", "contents": "Cyclic nucleotide-dependent protein kinase activity in acinar cells from guinea pig pancreas. Acinar cells from guinea pig pancreas possess two distinct protein kinase activities. Cyclic GMP-dependent kinase elutes as a single peak on diethylaminoethyl (DEAE)- cellulose chromatography, is not inhibited by protein kinase inhibitor, and has a greater affinity for cyclic GMP (half-maximal activation at 20 nM) than for cyclic AMP (half-maximal activation at 100 nM). Cyclic AMP-dependent kinase elutes as two peaks on DEAE-cellulose chromatography, is inhibited by protein kinase inhibitor, and has a greater affinity for cyclic AMP (half-maximal activation at 20 nM) than for cyclic GMP (half-maximal activation at 7 micrometer). Binding of cyclic 3H-nucleotides to the enzyme preparation was rapid, specific, temperature-dependent, and reversible, and there was a close correlation between the ability of a particular cyclic nucleotide to inhibit binding of cyclic 3H-nucleotide and its ability of a particular cyclic nucleotide to inhibit binding of cyclic H-nucleotide and its ability to activate protein kinase. Binding of cyclic 3H--nucleotide could not be described as a simple bimolecular reaction and native cyclic nucleotides accelerated the dissociation of bound, labeled cyclic nucleotide. Vasoactive intestinal peptide or secretin, each of which increases cellular cyclic AMP, caused endogenous activation of protein kinase and inhibition of cyclic [3H]AMP binding but did not alter bindings of cyclic [3H]GMP or cyclic [3H]AMP."}
{"id": "PMID:212342", "title": "A familial neuronal disease presenting as intestinal pseudoobstruction.", "content": "The purpose of this paper is to describe 2 siblings who had a generalized neurological disease which presented as intestinal pseudoobstruction. The siblings had 40-year histories of abdominal pain, distention, and vomiting as well as gait ataxia, small, irregular, poorly reactive pupils, dysarthria, absent deep tendon reflexes, and impaired vibratory and position senses. Compared with age-matched controls, they had inappropriate blood pressure responses to phenylephrine, the Valsalva maneuver, and upright posture, lack of sweating on warming, and pupillary denervation hypersensitivity. Radiographs revealed hyperactive, nonpropulsive contractions of a dilated esophagus and small intestine and extensive colonic diverticulosis. Esophageal manometry recorded repetitive, spontaneous, nonperistaltic waves and positive Mechyolyl tests. Postmortem examinations showed degeneration of the myenteric plexuses of the esophagus, small intestine, and colon of both patients. Myenteric plexus neurons were significantly reduced in number compared with 7 controls. About one-third of the siblings' neurons contained round, eosinophilic intranuclear inclusions, which, by histochemistry, were composed of protein by lacked RNA, DNA, carbohydrate, and fat. By electron microscopy the inclusions consisted of an irregular array of nonviral, nonmembrane-bounded filaments. Neurons and glial cells of the brain, spinal cord, dorsal root, and celiac plexus ganglia contained identical intranuclear inclusions. Intestinal smooth muscle was normal. These 2 siblings represent a unique disease in which degeneration of the myenteric plexus resulted in hyperactive but uncoordinated smooth muscle activity and the clinical syndrome of intestinal pseudoobstruction, the presenting manifestation of their neurological disease.", "contents": "A familial neuronal disease presenting as intestinal pseudoobstruction. The purpose of this paper is to describe 2 siblings who had a generalized neurological disease which presented as intestinal pseudoobstruction. The siblings had 40-year histories of abdominal pain, distention, and vomiting as well as gait ataxia, small, irregular, poorly reactive pupils, dysarthria, absent deep tendon reflexes, and impaired vibratory and position senses. Compared with age-matched controls, they had inappropriate blood pressure responses to phenylephrine, the Valsalva maneuver, and upright posture, lack of sweating on warming, and pupillary denervation hypersensitivity. Radiographs revealed hyperactive, nonpropulsive contractions of a dilated esophagus and small intestine and extensive colonic diverticulosis. Esophageal manometry recorded repetitive, spontaneous, nonperistaltic waves and positive Mechyolyl tests. Postmortem examinations showed degeneration of the myenteric plexuses of the esophagus, small intestine, and colon of both patients. Myenteric plexus neurons were significantly reduced in number compared with 7 controls. About one-third of the siblings' neurons contained round, eosinophilic intranuclear inclusions, which, by histochemistry, were composed of protein by lacked RNA, DNA, carbohydrate, and fat. By electron microscopy the inclusions consisted of an irregular array of nonviral, nonmembrane-bounded filaments. Neurons and glial cells of the brain, spinal cord, dorsal root, and celiac plexus ganglia contained identical intranuclear inclusions. Intestinal smooth muscle was normal. These 2 siblings represent a unique disease in which degeneration of the myenteric plexus resulted in hyperactive but uncoordinated smooth muscle activity and the clinical syndrome of intestinal pseudoobstruction, the presenting manifestation of their neurological disease."}
{"id": "PMID:212344", "title": "[Estrogen treatment of excessively tall girls (author's transl)].", "content": "20 girls, their age being between 8 to 13 years, with an actual height above the 97th percentile received 10,0 mg conjugated estrogens per day cyclicly or 0,3 mg ethinylestradiol continuously over a period of 0,3 to 3,8 years, in order to inhibit excessive growth. The duration of therapy ranged from 0,6 to 3,8 years regularly. Before and during treatment the patients were examined, and each time the expected final height was calculated based on the actual height and the bone age. The stage of puberty was defined according to Blizzard, and the determination of the bone age was performed as described by Tanner and Whitehouse. The extragenital side effects were also recorded. The effectiveness of the estrogen treatment, i. e. the reduction of the expected final height, depends on the chronological age, the skeletal age and the stage of puberty before therapy. It ranged between 0,5 and 5,1 cm. The earlier treatment was started the better were the results. The effectiveness was more obvious in cases with continuous estrogen treatment. No serious side effects could be observed.", "contents": "[Estrogen treatment of excessively tall girls (author's transl)]. 20 girls, their age being between 8 to 13 years, with an actual height above the 97th percentile received 10,0 mg conjugated estrogens per day cyclicly or 0,3 mg ethinylestradiol continuously over a period of 0,3 to 3,8 years, in order to inhibit excessive growth. The duration of therapy ranged from 0,6 to 3,8 years regularly. Before and during treatment the patients were examined, and each time the expected final height was calculated based on the actual height and the bone age. The stage of puberty was defined according to Blizzard, and the determination of the bone age was performed as described by Tanner and Whitehouse. The extragenital side effects were also recorded. The effectiveness of the estrogen treatment, i. e. the reduction of the expected final height, depends on the chronological age, the skeletal age and the stage of puberty before therapy. It ranged between 0,5 and 5,1 cm. The earlier treatment was started the better were the results. The effectiveness was more obvious in cases with continuous estrogen treatment. No serious side effects could be observed."}
{"id": "PMID:212352", "title": "Changes in the activity of hydrolytic enzymes in the brain of rats intoxicated by ethyl-mercury-p-toluene-sulfanilide.", "content": "A histochemical study concerning the activity of phosphatases and esterases of the brain has been undertaken in rats experimentally intoxicated by the fungicide ethyl-mercury-p-toluenesulfanilide (EMTS). The results have shown that compared with other mercury compounds, both organic and inorganic ones, such as corrosive sublimate and calomel, EMTS proved to be a less induced of alterations in the activity of cerebral hydrolases. The brains of animals intoxicated by EMTS revealed a notable decrease of ATP-ase and acid phosphatase activity as well as a moderate drop of AChE activity. Instead, the neuronal TPPase activity was distinctly elevated. Degenerative changes of neurons were observed in various regions of the experimental brains, the pyramidal cells of the Ammon's horn being affected most severely.", "contents": "Changes in the activity of hydrolytic enzymes in the brain of rats intoxicated by ethyl-mercury-p-toluene-sulfanilide. A histochemical study concerning the activity of phosphatases and esterases of the brain has been undertaken in rats experimentally intoxicated by the fungicide ethyl-mercury-p-toluenesulfanilide (EMTS). The results have shown that compared with other mercury compounds, both organic and inorganic ones, such as corrosive sublimate and calomel, EMTS proved to be a less induced of alterations in the activity of cerebral hydrolases. The brains of animals intoxicated by EMTS revealed a notable decrease of ATP-ase and acid phosphatase activity as well as a moderate drop of AChE activity. Instead, the neuronal TPPase activity was distinctly elevated. Degenerative changes of neurons were observed in various regions of the experimental brains, the pyramidal cells of the Ammon's horn being affected most severely."}
{"id": "PMID:212356", "title": "[Electromyographic and electroneurographic findings in bronchial carcinoma].", "content": "Twenty one patients with confirmed bronchial carcinoma were checked by clinical, electromyographical and electroneurographical methods. None of these patients underwent cytostatic therapy. Clinical findings were: 4 patients suffered from polyneuropathy (PNP) and myelopathy (MP). 3 patients had PNP alone, 3 had MP. We could support these findings by EMG in 7 patients with PNP. 4 of these cases had a lowered motor nerve conduction velocity (MNCV). In 4 cases without clinical symptoms we could show a lowered MNCV at the distal legs and affection of the motor neuron by EMG. 3 further cases without clinical symptoms showed only a lowered MNCV. 5 patients had proximal pareses. Signs of MP were not found in these cases. In conclusion we found a significantly lowered MNCV in 5 cases: only two of these showed clinical signs of PNP. Pathological EMG changes were mostly found in patients with squamous cell carcinoma, sometimes also in patients with oat cell carcinoma. Thus, clinical, electromyographic and electroneurographic findings did not always correlate in our cases.", "contents": "[Electromyographic and electroneurographic findings in bronchial carcinoma]. Twenty one patients with confirmed bronchial carcinoma were checked by clinical, electromyographical and electroneurographical methods. None of these patients underwent cytostatic therapy. Clinical findings were: 4 patients suffered from polyneuropathy (PNP) and myelopathy (MP). 3 patients had PNP alone, 3 had MP. We could support these findings by EMG in 7 patients with PNP. 4 of these cases had a lowered motor nerve conduction velocity (MNCV). In 4 cases without clinical symptoms we could show a lowered MNCV at the distal legs and affection of the motor neuron by EMG. 3 further cases without clinical symptoms showed only a lowered MNCV. 5 patients had proximal pareses. Signs of MP were not found in these cases. In conclusion we found a significantly lowered MNCV in 5 cases: only two of these showed clinical signs of PNP. Pathological EMG changes were mostly found in patients with squamous cell carcinoma, sometimes also in patients with oat cell carcinoma. Thus, clinical, electromyographic and electroneurographic findings did not always correlate in our cases."}
{"id": "PMID:212360", "title": "Homozygosity of adenylate kinase allele 3: two cases.", "content": "The phenotype AK 3.3 in the isoenzyme system of human adenylate kinase has been found in two members of the Wayampi population of French Guiana.", "contents": "Homozygosity of adenylate kinase allele 3: two cases. The phenotype AK 3.3 in the isoenzyme system of human adenylate kinase has been found in two members of the Wayampi population of French Guiana."}
{"id": "PMID:212361", "title": "Mitogen-induced activation of stable E-rosettes by human lymphocytes.", "content": "Following on an earlier study which demonstrated that PHA can activate human lymphocytes to form temperature-stable (37 degrees C.) E-rosettes with sheep red blood cells, a number of other mitogens were tested. These included Concanavalin A, pokeweed mitogen, soybean agglutinin, sodium periodate, and galactose oxidase. All except soybean agglutinin demonstrated the capability to activate lymphocytes to form stable E-rosettes.", "contents": "Mitogen-induced activation of stable E-rosettes by human lymphocytes. Following on an earlier study which demonstrated that PHA can activate human lymphocytes to form temperature-stable (37 degrees C.) E-rosettes with sheep red blood cells, a number of other mitogens were tested. These included Concanavalin A, pokeweed mitogen, soybean agglutinin, sodium periodate, and galactose oxidase. All except soybean agglutinin demonstrated the capability to activate lymphocytes to form stable E-rosettes."}
{"id": "PMID:212366", "title": "Antibody-dependent cellular cytotoxicity against Epstein-Barr virus-associated antigens in African patients with nasopharyngeal carcinoma.", "content": "Antibody-dependent cellular cytotoxicity (ADCC) was performed on serum samples from African patients with nasopharyngeal carcinoma (NPC) to determine whether antibody titers determined by this assay might be of prognostic value in this disease. The serum donors were divided into two groups: (1) those individuals who died within 2 years following diagnosis of NPC; and (2) individuals who responded well to therapy and surivived for more than 2 years following diagnosis. The ADCC GMT for the survivor group was significantly higher than the GMT for non-survivors (%5,410 versus 615). Interestingly, there were a number of discordant sera in the non-survivor group that had very low ADCC titers (less than 240) at diagnosis in the presence of high VCA titers. When ADCC titers were compared with anti-EA or IgA antibody titers to VCA, a statistically significant inverse correlation was noted. These data suggest that ADCC titers might be of prognostic importance in African NPC.", "contents": "Antibody-dependent cellular cytotoxicity against Epstein-Barr virus-associated antigens in African patients with nasopharyngeal carcinoma. Antibody-dependent cellular cytotoxicity (ADCC) was performed on serum samples from African patients with nasopharyngeal carcinoma (NPC) to determine whether antibody titers determined by this assay might be of prognostic value in this disease. The serum donors were divided into two groups: (1) those individuals who died within 2 years following diagnosis of NPC; and (2) individuals who responded well to therapy and surivived for more than 2 years following diagnosis. The ADCC GMT for the survivor group was significantly higher than the GMT for non-survivors (%5,410 versus 615). Interestingly, there were a number of discordant sera in the non-survivor group that had very low ADCC titers (less than 240) at diagnosis in the presence of high VCA titers. When ADCC titers were compared with anti-EA or IgA antibody titers to VCA, a statistically significant inverse correlation was noted. These data suggest that ADCC titers might be of prognostic importance in African NPC."}
{"id": "PMID:212363", "title": "Some photoresponses of isolated tissue preparations to ultraviolet light in the presence of photosensitizers.", "content": "Responses of isolated tissue preparations to ultraviolet (UV) light were studied with and without the presence of photosensitizers like eosin, fluorescein and sodium nitrite. Exposure to UV light in the presence of sodium nitrite induced consistent relaxation of rat duodenum. The photorelaxation was found to be related to the concentration of sodium nitrite. Adrenergic or cholinergic mechanisms do not seem to be involved. The isolated rat duodenum preparation exhibited quantitatively consistent photoresponse for 3 to 4 hr at its normal tone obviating the need for additional spasmogens as needed with other preparations. The preparation is a suitable test model for the study of photobiologic response evoked by UV light.", "contents": "Some photoresponses of isolated tissue preparations to ultraviolet light in the presence of photosensitizers. Responses of isolated tissue preparations to ultraviolet (UV) light were studied with and without the presence of photosensitizers like eosin, fluorescein and sodium nitrite. Exposure to UV light in the presence of sodium nitrite induced consistent relaxation of rat duodenum. The photorelaxation was found to be related to the concentration of sodium nitrite. Adrenergic or cholinergic mechanisms do not seem to be involved. The isolated rat duodenum preparation exhibited quantitatively consistent photoresponse for 3 to 4 hr at its normal tone obviating the need for additional spasmogens as needed with other preparations. The preparation is a suitable test model for the study of photobiologic response evoked by UV light."}
{"id": "PMID:212367", "title": "Antibody patterns to herpesviruses in Kaposi's sarcoma. II. Serological association of American Kaposi's sarcoma with cytomegalovirus.", "content": "The prominent finding of this extended serologic analysis on American and African Kaposi's sarcoma (KS) patients and appropriately matched control groups is the detection of a specific serologic association of cytomegalovirus (CMV) with American KS patients. All American KS sera contained CMV antibodies and their geometric mean titers (GMT) were significantly higher than those in sera of melanoma patients (GMT ratio k = 5.3 to 7.7 by complement fixation [CF], k = 8.9 by indirect hemagglutination [IHA]) or in sera of age- and sex-matched healthy controls (k = 12.6 to 16.0 by CF, k = 12.6 by IHA). The result is strongly reminiscent of the data obtained previously for European KS. Although the GMT to CMV of African KS patients were similar to the GMT of the American KS groups, their significance cannot be demonstrated due to the high background of CMV infections in the control groups. Complex mechanisms are hypothesized, by analogy with the Epstein-Barr virus (EBV) involvement in Burkitt's lymphoma (BL), for a CMV involvement in the development of KS.", "contents": "Antibody patterns to herpesviruses in Kaposi's sarcoma. II. Serological association of American Kaposi's sarcoma with cytomegalovirus. The prominent finding of this extended serologic analysis on American and African Kaposi's sarcoma (KS) patients and appropriately matched control groups is the detection of a specific serologic association of cytomegalovirus (CMV) with American KS patients. All American KS sera contained CMV antibodies and their geometric mean titers (GMT) were significantly higher than those in sera of melanoma patients (GMT ratio k = 5.3 to 7.7 by complement fixation [CF], k = 8.9 by indirect hemagglutination [IHA]) or in sera of age- and sex-matched healthy controls (k = 12.6 to 16.0 by CF, k = 12.6 by IHA). The result is strongly reminiscent of the data obtained previously for European KS. Although the GMT to CMV of African KS patients were similar to the GMT of the American KS groups, their significance cannot be demonstrated due to the high background of CMV infections in the control groups. Complex mechanisms are hypothesized, by analogy with the Epstein-Barr virus (EBV) involvement in Burkitt's lymphoma (BL), for a CMV involvement in the development of KS."}
{"id": "PMID:212368", "title": "Genetics of SV40 T-antigen expression: studies of twins, heritable syndromes and cancer families.", "content": "Susceptibility of human skin fibroblasts to SV40 virus infection has been suggested as a marker of cancer risk. To evaluate the role of heritable factors in the regulation of SV40 T-antigen, fibroblasts from 9 pairs of identical twins and 129 members of cancer-prone families, including 16 with cancer, were tested in a 3-day immunofluorescence assay. In the twin study, the variance of T-antigen values was significantly less in identical than in fraternal or non-twin sibs, suggesting a heritable component in the regulation of SV40 infection. In the families, T-antigen values of parents and children were compared to models of Mendelian inheritance. At least three modes of inheritance--autosomal dominant, recessive, and X-linker--were observed. The distribution of offspring values compared to those of their parents suggested that interaction of multiple genetic factors influences the T-antigen value in individual patients. With the exception of Fanconi's anemia, the values for patients with cancer or predisposing syndromes were not uniformly elevated. The utility of this assay as a marker of cancer risk appears limited because of the complexity of factors that influence T-antigen expression in individual cases.", "contents": "Genetics of SV40 T-antigen expression: studies of twins, heritable syndromes and cancer families. Susceptibility of human skin fibroblasts to SV40 virus infection has been suggested as a marker of cancer risk. To evaluate the role of heritable factors in the regulation of SV40 T-antigen, fibroblasts from 9 pairs of identical twins and 129 members of cancer-prone families, including 16 with cancer, were tested in a 3-day immunofluorescence assay. In the twin study, the variance of T-antigen values was significantly less in identical than in fraternal or non-twin sibs, suggesting a heritable component in the regulation of SV40 infection. In the families, T-antigen values of parents and children were compared to models of Mendelian inheritance. At least three modes of inheritance--autosomal dominant, recessive, and X-linker--were observed. The distribution of offspring values compared to those of their parents suggested that interaction of multiple genetic factors influences the T-antigen value in individual patients. With the exception of Fanconi's anemia, the values for patients with cancer or predisposing syndromes were not uniformly elevated. The utility of this assay as a marker of cancer risk appears limited because of the complexity of factors that influence T-antigen expression in individual cases."}
{"id": "PMID:212371", "title": "Interaction of the B95-8 and P3HR-1 substrains of Epstein-Barr virus (EBV) with peripheral human lymphocytes.", "content": "Two substrains of the Epstein-Barr virus derived from the B95-8 and P3HR-1 cell lines were studied for their interaction with human peripheral lymphocytes. It has been previously shown that B95-8 virus has and P3HR-1 virus lacks lymphocyte-transforming (\"immortalizing\") properties. DNA stimulation induced by B95-8 virus showed a good correlation with the number of surface Ig-positive cells. P3HR-1 virus added before B95-8 virus completely abolished the stimulation of DNA synthesis. It also prevented EBNA induction by B95-8 virus. P3HR-1 virus added after B95-8 virus diminished DNA stimulation by the latter in a time-dependent fashion. P3HR-1 virus did not inhibit DNA stimulation by phytohaemagglutinin but was inhibitory if added before a B cell mitogen (Staphylococcus Aureus). The origin of P3HR-1 virus and its relationship to the transformation process are discussed.", "contents": "Interaction of the B95-8 and P3HR-1 substrains of Epstein-Barr virus (EBV) with peripheral human lymphocytes. Two substrains of the Epstein-Barr virus derived from the B95-8 and P3HR-1 cell lines were studied for their interaction with human peripheral lymphocytes. It has been previously shown that B95-8 virus has and P3HR-1 virus lacks lymphocyte-transforming (\"immortalizing\") properties. DNA stimulation induced by B95-8 virus showed a good correlation with the number of surface Ig-positive cells. P3HR-1 virus added before B95-8 virus completely abolished the stimulation of DNA synthesis. It also prevented EBNA induction by B95-8 virus. P3HR-1 virus added after B95-8 virus diminished DNA stimulation by the latter in a time-dependent fashion. P3HR-1 virus did not inhibit DNA stimulation by phytohaemagglutinin but was inhibitory if added before a B cell mitogen (Staphylococcus Aureus). The origin of P3HR-1 virus and its relationship to the transformation process are discussed."}
{"id": "PMID:212373", "title": "Differences in the capacity of simian virus 40 (SV40) tumor antigens on cells, membranes and in soluble form to induce transplantation immunity in hamsters and mice.", "content": "The immunogenicity of the SV40 tumor-specific transplantation antigen (TSTA) on cells, cell particulates and solubilized membranes was studied in mice and in Syrian hamsters. Immunizations were done with various concentrations of tissue-culture-passaged, non-virus-releasing transformed cells, purified cell membranes and in some cases purified nuclei and papain-solubilized membranes obtained from several species, including the mouse, hamster, man, and sheep. All transformed cell lines were T-antigen-positive. The immunosensitive mKSA line of BALB/c mice and the immunosensitive SV34 cell line of the hamster were used for tumor challenge. All materials, regardless of source and of type of preparation, were strikingly immunogenic in the mouse but only SV40 virus and SV34 (hamster) cells provided protection against tumor cell challenge in the hamster. Also, in a limited study, BKV-transformed hamster cells and purified cell membranes and JCV-transformed hamster cells were found to be immunogenic by the tumor rejection assay in the mouse but not in the hamster. SV40 immunization did not protect the hamster against BKV- and JCV-transformed hamster cells. These results are discussed in terms of possible different specificities resident on the TSTA molecule.", "contents": "Differences in the capacity of simian virus 40 (SV40) tumor antigens on cells, membranes and in soluble form to induce transplantation immunity in hamsters and mice. The immunogenicity of the SV40 tumor-specific transplantation antigen (TSTA) on cells, cell particulates and solubilized membranes was studied in mice and in Syrian hamsters. Immunizations were done with various concentrations of tissue-culture-passaged, non-virus-releasing transformed cells, purified cell membranes and in some cases purified nuclei and papain-solubilized membranes obtained from several species, including the mouse, hamster, man, and sheep. All transformed cell lines were T-antigen-positive. The immunosensitive mKSA line of BALB/c mice and the immunosensitive SV34 cell line of the hamster were used for tumor challenge. All materials, regardless of source and of type of preparation, were strikingly immunogenic in the mouse but only SV40 virus and SV34 (hamster) cells provided protection against tumor cell challenge in the hamster. Also, in a limited study, BKV-transformed hamster cells and purified cell membranes and JCV-transformed hamster cells were found to be immunogenic by the tumor rejection assay in the mouse but not in the hamster. SV40 immunization did not protect the hamster against BKV- and JCV-transformed hamster cells. These results are discussed in terms of possible different specificities resident on the TSTA molecule."}
{"id": "PMID:212374", "title": "Virus-induced papillomas of the alimentary tract of cattle.", "content": "An abattoir survey was carried out to determine the incidence and aetiology of squamous papillomas of the alimentary tract of cattle in Scotland and North England as they were suspected of being involved in the genesis of alimentary carcinoma in certain localized geographical areas. A total of 7,746 cattle of a wide age range was examined. Various subsets of this number were subjected to analyses of certain specific factors. The calculated overall incidence was 19% and the detailed site incidence and tumour multiplicity are given. The sites at which papillomas were found were identical with those at which carcinoma had been noted in animals from a high-cancer area. The number of sites affected by papilloma and the tumour multiplicity were much lower in the general population than in the high-cancer area. Inclusion bodies, identified by electronmicroscopy as virus, were found in tumour cell nuclei and a typical papilloma virus was purified from the tumours. The structure of the tumours is described and the possible plurality of bovine papilloma-viruses is discussed in the light of recent findings in the human viruses. The general interest of a naturally occurring and geographically localized oncogenic system, in which an environmental carcinogen and a virus might be involved, is extended.", "contents": "Virus-induced papillomas of the alimentary tract of cattle. An abattoir survey was carried out to determine the incidence and aetiology of squamous papillomas of the alimentary tract of cattle in Scotland and North England as they were suspected of being involved in the genesis of alimentary carcinoma in certain localized geographical areas. A total of 7,746 cattle of a wide age range was examined. Various subsets of this number were subjected to analyses of certain specific factors. The calculated overall incidence was 19% and the detailed site incidence and tumour multiplicity are given. The sites at which papillomas were found were identical with those at which carcinoma had been noted in animals from a high-cancer area. The number of sites affected by papilloma and the tumour multiplicity were much lower in the general population than in the high-cancer area. Inclusion bodies, identified by electronmicroscopy as virus, were found in tumour cell nuclei and a typical papilloma virus was purified from the tumours. The structure of the tumours is described and the possible plurality of bovine papilloma-viruses is discussed in the light of recent findings in the human viruses. The general interest of a naturally occurring and geographically localized oncogenic system, in which an environmental carcinogen and a virus might be involved, is extended."}
{"id": "PMID:212376", "title": "Demonstration of specific cell-mediated anti-tumor immunity in lung cancer to autologous tissue extracts.", "content": "Cell-mediated immunity (CMI) of lung cancer patients to autologous tumor antigens was assessed by mixed lymphocyte tumor interactions (MLTI) as measured in a microculture (200 microliter) lymphocyte proliferation (LP) assay. Positive lymphoproleferative responses were observed with cryopreserved intact mitomycin-C-treated autologous tumor cells (8/12 or 67% patients reactive) and with hypotonic membrane extracts (HMP) of tumor cells (28/40 or 70%). Good correlation was found between reactivity to tumor cells and extracts in parallel testing. In contrast, HMP of autologous normal lung tissue elicited very little LP reactivity, with only one patient giving a weak response by the SI criterion and low level of n cpm. Upon repeat testing, many patients gave reproducibly positive LP responses to tumor HMP. Patients at all clinical stages of disease and with different histologic tumor types had a similar proportion of HMP reactivity. Most reactive patients responded to a broad range of protein concentrations of tumor HMP, and LP responses were frequently elicited with 1 microgram or less of HMP. Thus, HMP appear to afford a convenient source of reactive tumor antigen for assessing anti-tumor immunity.", "contents": "Demonstration of specific cell-mediated anti-tumor immunity in lung cancer to autologous tissue extracts. Cell-mediated immunity (CMI) of lung cancer patients to autologous tumor antigens was assessed by mixed lymphocyte tumor interactions (MLTI) as measured in a microculture (200 microliter) lymphocyte proliferation (LP) assay. Positive lymphoproleferative responses were observed with cryopreserved intact mitomycin-C-treated autologous tumor cells (8/12 or 67% patients reactive) and with hypotonic membrane extracts (HMP) of tumor cells (28/40 or 70%). Good correlation was found between reactivity to tumor cells and extracts in parallel testing. In contrast, HMP of autologous normal lung tissue elicited very little LP reactivity, with only one patient giving a weak response by the SI criterion and low level of n cpm. Upon repeat testing, many patients gave reproducibly positive LP responses to tumor HMP. Patients at all clinical stages of disease and with different histologic tumor types had a similar proportion of HMP reactivity. Most reactive patients responded to a broad range of protein concentrations of tumor HMP, and LP responses were frequently elicited with 1 microgram or less of HMP. Thus, HMP appear to afford a convenient source of reactive tumor antigen for assessing anti-tumor immunity."}
{"id": "PMID:212377", "title": "Recovery of transforming EBV from non-producer cells after superinfection with non-transforming P3HR-1 EBV.", "content": "Cells of the Raji and NC37 lines can be induced by chemical inducers, such as BrdUrd and IdUrd, or the tumor-promoter TPA to EA-expression only, but do not reveal any VCA synthesis. After superinfection by nontransforming P3HR-1 EBV, however, a varying percentage of the cell population shows VCA synthesis and releases infectious viral particles. The recovered virus differs biologically from P3HR-1 EBV since it transforms human umbilical cord blood lymphocytes into EBNA-positive lymphoblastoid cell lines. Cells of these established lines are susceptible to renewed infection by P3HR-1 EBV which results in EA induction and VCA synthesis. Only cells of one line, NC37-R1, spontaneously produce VCA and EBV particles, which reveal transforming properties and do not induce EA upon superinfection of Raji cells. Infection of P3HR-1 EBV-converted BJA-B cells also leads to EA and VCA induction and the release of viral particles. In contrast to particles recovered from Raji and NC37 cells, no transforming activity was detectable in these virus preparations. According to these data, we propose that viral genomes persisting within Raji and NC37 cells are defective and become complemented by the superinfecting P3HR-1 virus.", "contents": "Recovery of transforming EBV from non-producer cells after superinfection with non-transforming P3HR-1 EBV. Cells of the Raji and NC37 lines can be induced by chemical inducers, such as BrdUrd and IdUrd, or the tumor-promoter TPA to EA-expression only, but do not reveal any VCA synthesis. After superinfection by nontransforming P3HR-1 EBV, however, a varying percentage of the cell population shows VCA synthesis and releases infectious viral particles. The recovered virus differs biologically from P3HR-1 EBV since it transforms human umbilical cord blood lymphocytes into EBNA-positive lymphoblastoid cell lines. Cells of these established lines are susceptible to renewed infection by P3HR-1 EBV which results in EA induction and VCA synthesis. Only cells of one line, NC37-R1, spontaneously produce VCA and EBV particles, which reveal transforming properties and do not induce EA upon superinfection of Raji cells. Infection of P3HR-1 EBV-converted BJA-B cells also leads to EA and VCA induction and the release of viral particles. In contrast to particles recovered from Raji and NC37 cells, no transforming activity was detectable in these virus preparations. According to these data, we propose that viral genomes persisting within Raji and NC37 cells are defective and become complemented by the superinfecting P3HR-1 virus."}
{"id": "PMID:212378", "title": "Aryl hydrocarbon hydroxylase in persons with lung or laryngeal cancer.", "content": "To test whether the distribution of AHH inducibility is shifted toward the high end of the range in patients who had lung and laryngeal cancer, we measured this trait in 59 patients (32 lung and 27 laryngeal) who had resectable tumors and had been disease-free for a period of time. The advantage of selecting patients who were free of clinical disease was that measurement of their AHH inducibility should not have been affected by the disease state. Patient and control populations showed no difference in basal and induced AHH activity of AHH inducibility. The mean AHH inducibility in patients who had lung cancer was 3.20 +/- 0.20; in patients who had laryngeal cancer 2.96 +/- 0.18, and for all controls 3.29 +/- 0.04 (no significant difference at p = 0 05). Further analysis of the distribution of AHH inducibility in the patient group compared to controls showed no suggestion of a shift toward the higher end of the range in patients who had lung and laryngeal cancer.", "contents": "Aryl hydrocarbon hydroxylase in persons with lung or laryngeal cancer. To test whether the distribution of AHH inducibility is shifted toward the high end of the range in patients who had lung and laryngeal cancer, we measured this trait in 59 patients (32 lung and 27 laryngeal) who had resectable tumors and had been disease-free for a period of time. The advantage of selecting patients who were free of clinical disease was that measurement of their AHH inducibility should not have been affected by the disease state. Patient and control populations showed no difference in basal and induced AHH activity of AHH inducibility. The mean AHH inducibility in patients who had lung cancer was 3.20 +/- 0.20; in patients who had laryngeal cancer 2.96 +/- 0.18, and for all controls 3.29 +/- 0.04 (no significant difference at p = 0 05). Further analysis of the distribution of AHH inducibility in the patient group compared to controls showed no suggestion of a shift toward the higher end of the range in patients who had lung and laryngeal cancer."}
{"id": "PMID:212382", "title": "Influences on the density of beta-adrenergic receptors in the cornea and iris--ciliary body of the rabbit.", "content": "By measurement of the specific binding of 3H-dihydroalprenolol, the densities of beta-adrenergic receptors on membranes prepared from homogenized corneas and iris--ciliary bodies of rabbits were studied. Sympathetic denervation, as a result of subconjunctival treatment with 6-hydroxydopamine, causes an increase in the density of beta-adrenergic receptors in membranes prepared from the ipsilateral iris--ciliary body but not the cornea. Topical treatment with epinephrine for 5 days causes a decrease in the density of beta-adrenergic receptors in membranes prepared from cornea and iris-ciliary body, whereas similar treatment with timolol causes an increase in the density of beta-adrenergic receptors. In the cornea, the decrease in receptor density that occurs following in vivo treatment with epinephrine is associated with a decreased ability to synthesize cyclic AMP, whereas the increase in receptor density that occurs following in vivo treatment with timolol is not associated with an altered ability to synthesize cyclic AMP. Our results indicate that the density of beta-adrenergic receptors in the anterior segment of the eye is inversely related to the level of adrenergic stimulation to the tissue but that the ability of a tissue to synthesize cyclic AMP does not necessarily parallel the change in receptor density.", "contents": "Influences on the density of beta-adrenergic receptors in the cornea and iris--ciliary body of the rabbit. By measurement of the specific binding of 3H-dihydroalprenolol, the densities of beta-adrenergic receptors on membranes prepared from homogenized corneas and iris--ciliary bodies of rabbits were studied. Sympathetic denervation, as a result of subconjunctival treatment with 6-hydroxydopamine, causes an increase in the density of beta-adrenergic receptors in membranes prepared from the ipsilateral iris--ciliary body but not the cornea. Topical treatment with epinephrine for 5 days causes a decrease in the density of beta-adrenergic receptors in membranes prepared from cornea and iris-ciliary body, whereas similar treatment with timolol causes an increase in the density of beta-adrenergic receptors. In the cornea, the decrease in receptor density that occurs following in vivo treatment with epinephrine is associated with a decreased ability to synthesize cyclic AMP, whereas the increase in receptor density that occurs following in vivo treatment with timolol is not associated with an altered ability to synthesize cyclic AMP. Our results indicate that the density of beta-adrenergic receptors in the anterior segment of the eye is inversely related to the level of adrenergic stimulation to the tissue but that the ability of a tissue to synthesize cyclic AMP does not necessarily parallel the change in receptor density."}
{"id": "PMID:212383", "title": "Effects of epinephrine, indomethacin, acetylsalicyclic acid, dexamethasone, and cyclic AMP on the in vitro activity of lysosomal hyaluronidase from the rabbit iris.", "content": "The effects of epinephrine, indomethacin, acetylsalicylic acid, dexamethasone, and cyclic AMP on lysosomal hyaluronidase activity in in the rabbit iris were studied in vitro. Indomethacin and acetylsalicylic acid inhibited the lysosomal hyaluronidase activity. Dexamethasone and cyclic AMP (adenosine-3',5'-cyclic monophosphate) had little effect on the enzyme activity. Epinephrine activated the enzyme activity. These drugs had no effect on the activities of either bovine testicular hyaluronidase or rabbit iridial acid phosphatase. The possible role of lysosomal hyaluronidase in the rabbit eye and the drug effects were considered.", "contents": "Effects of epinephrine, indomethacin, acetylsalicyclic acid, dexamethasone, and cyclic AMP on the in vitro activity of lysosomal hyaluronidase from the rabbit iris. The effects of epinephrine, indomethacin, acetylsalicylic acid, dexamethasone, and cyclic AMP on lysosomal hyaluronidase activity in in the rabbit iris were studied in vitro. Indomethacin and acetylsalicylic acid inhibited the lysosomal hyaluronidase activity. Dexamethasone and cyclic AMP (adenosine-3',5'-cyclic monophosphate) had little effect on the enzyme activity. Epinephrine activated the enzyme activity. These drugs had no effect on the activities of either bovine testicular hyaluronidase or rabbit iridial acid phosphatase. The possible role of lysosomal hyaluronidase in the rabbit eye and the drug effects were considered."}
{"id": "PMID:212384", "title": "Leukocyte migration inhibitory factor in HSV infections.", "content": "The cell-mediated immune (CMI) response as measured by a direct assay of leukocyte migration inhibition factor (LMIF) was determined in a population of patients with recurrent herpes simplex virus (HSV) infections in the quiescent stage as well as in healthy volunteers. The migration of leukocytes incubated in the presence of HSV antigens was compared to that without viral antigens for the calculation of the migration index (MI). Eleven of 41 control subjects (16.8%) had a MI below 0.8, indicating a positive CMI response. In contrast, all the herpes patients tested had a MI above 0.8, suggesting an impairment in the production of LMIF at this stage of their disease. This difference was statistically significant (t = 4.296; p less than 0.001) and was not dependent on the age of the population. This study indicates that individuals with recurrent HSV infections have impaired CMI response betweeen attacks which may be associated with the stage of the disease.", "contents": "Leukocyte migration inhibitory factor in HSV infections. The cell-mediated immune (CMI) response as measured by a direct assay of leukocyte migration inhibition factor (LMIF) was determined in a population of patients with recurrent herpes simplex virus (HSV) infections in the quiescent stage as well as in healthy volunteers. The migration of leukocytes incubated in the presence of HSV antigens was compared to that without viral antigens for the calculation of the migration index (MI). Eleven of 41 control subjects (16.8%) had a MI below 0.8, indicating a positive CMI response. In contrast, all the herpes patients tested had a MI above 0.8, suggesting an impairment in the production of LMIF at this stage of their disease. This difference was statistically significant (t = 4.296; p less than 0.001) and was not dependent on the age of the population. This study indicates that individuals with recurrent HSV infections have impaired CMI response betweeen attacks which may be associated with the stage of the disease."}
{"id": "PMID:212381", "title": "Meningo-encephalitis presenting as an acute paranoid psychosis.", "content": "A twenty-seven year old women with meningo-encephalitis and paranoid symptoms is presented. The patient was admitted to a psychiatric unit where, two months previously, her brother had been under treatment for a paranoid schizophrenic episode. The diagnostic lumbar puncture was performed after several days of increasing periods of disorientation, stupor, incontinence, posturing, and perseveration. There was no fever, no signs of meningeal irritation, and no localizing neurologic deficit. The problem of recognizing organic brain disease presenting as an acute psychotic episode is discussed. In this case, the positive family history was given inappropriate emphasis, while the good pre-morbid adjustment of the patient and the symptoms of confusion and headache were inadequately considered. Viral meningo-encephalitis, particularly that due to herpes simplex, often presents with a picture of behavioral abnormalities and minimal physical signs, and is easily confused with a functional process.", "contents": "Meningo-encephalitis presenting as an acute paranoid psychosis. A twenty-seven year old women with meningo-encephalitis and paranoid symptoms is presented. The patient was admitted to a psychiatric unit where, two months previously, her brother had been under treatment for a paranoid schizophrenic episode. The diagnostic lumbar puncture was performed after several days of increasing periods of disorientation, stupor, incontinence, posturing, and perseveration. There was no fever, no signs of meningeal irritation, and no localizing neurologic deficit. The problem of recognizing organic brain disease presenting as an acute psychotic episode is discussed. In this case, the positive family history was given inappropriate emphasis, while the good pre-morbid adjustment of the patient and the symptoms of confusion and headache were inadequately considered. Viral meningo-encephalitis, particularly that due to herpes simplex, often presents with a picture of behavioral abnormalities and minimal physical signs, and is easily confused with a functional process."}
{"id": "PMID:212385", "title": "Free radicals produced in human lenses by a biphotonic process.", "content": "Cataractous and noncataractous human lenses were irradiated with ultraviolet (UV) light, and the resulting triplet and radical species were studied by electron paramagnetic resonance spectroscopy. Evidence is presented that free radicals are produced by a biphotonic process involving tryptophan as an intermediate triplet. This makes free radical production energetically feasible. A possible link between incident UV light and cataract formation is suggested.", "contents": "Free radicals produced in human lenses by a biphotonic process. Cataractous and noncataractous human lenses were irradiated with ultraviolet (UV) light, and the resulting triplet and radical species were studied by electron paramagnetic resonance spectroscopy. Evidence is presented that free radicals are produced by a biphotonic process involving tryptophan as an intermediate triplet. This makes free radical production energetically feasible. A possible link between incident UV light and cataract formation is suggested."}
{"id": "PMID:212387", "title": "Wescodyne: lack of activity against poliovirus in the presence of organic matter.", "content": "The National Institute of Health Guidelines for Recombinant DNA Research recommends 2% aqueous Wescodyne, an iodophore that is used in many hospitals and laboratories as a disinfectant, as a decontaminant for biological safety cabinets and 5% for a spill outside a cabinet. A contact time of 10 to 15 minutes was given for the 2% solution and 20 minutes was considered adequate for the 5% concentration. The results indicate: 1. Aqueous Wescodyne (5%) is ineffective when used for 80 minutes against poliovirus in a test mixture containing 8.5% bovine serum albumin (a mixture equivalent in protein concentration to the higher range in serum). 2. Wescodyne (10%) employed under the same conditions for 40 minutes is also ineffective. 3. Wescodyne (10% v/v) in 50% ethanol (w/w) was effective and this mixture, originally recommended for hand washing, should be considered for use in biohazard situations, particularly for decontamination of work surfaces and biological safety cabinets. These results are of significance for if a virucide cannot inactivate poliovirus one would be concerned about using the virucide against hepatitis B or SV40 viruses.", "contents": "Wescodyne: lack of activity against poliovirus in the presence of organic matter. The National Institute of Health Guidelines for Recombinant DNA Research recommends 2% aqueous Wescodyne, an iodophore that is used in many hospitals and laboratories as a disinfectant, as a decontaminant for biological safety cabinets and 5% for a spill outside a cabinet. A contact time of 10 to 15 minutes was given for the 2% solution and 20 minutes was considered adequate for the 5% concentration. The results indicate: 1. Aqueous Wescodyne (5%) is ineffective when used for 80 minutes against poliovirus in a test mixture containing 8.5% bovine serum albumin (a mixture equivalent in protein concentration to the higher range in serum). 2. Wescodyne (10%) employed under the same conditions for 40 minutes is also ineffective. 3. Wescodyne (10% v/v) in 50% ethanol (w/w) was effective and this mixture, originally recommended for hand washing, should be considered for use in biohazard situations, particularly for decontamination of work surfaces and biological safety cabinets. These results are of significance for if a virucide cannot inactivate poliovirus one would be concerned about using the virucide against hepatitis B or SV40 viruses."}
{"id": "PMID:212389", "title": "An organ culture model for study of biochemical development of fetal rat lung.", "content": "We have developed a short-term organ culture model for the study of the biochemical and morphological development of late gestation fetal rat lung. Explants (1 mm3) of 19-day lung were cultured in an oxygen enriched environment in the presence of synthetic serum-free medium for 3 days. Morphological maturation continued in culture. The rate of incorporation of choline into disaturated phosphatidylcholine and the content of this phospholipid in the explants increased in vitro in a pattern very similar to that which occurs in vivo. The activities of choline kinase and cholinephosphotransferase were also similar in cultured lung and in vivo. Studies of glucose oxidation to CO2 provided additional evidence that the explants remained viable in culture. The explants retained the sensitivity of fetal lung to hormonal action. This was demonstrated by the stimulation of choline incorporation into phospholipid by cyclic AMP and an increase in the glycogen content after exposure to insulin.", "contents": "An organ culture model for study of biochemical development of fetal rat lung. We have developed a short-term organ culture model for the study of the biochemical and morphological development of late gestation fetal rat lung. Explants (1 mm3) of 19-day lung were cultured in an oxygen enriched environment in the presence of synthetic serum-free medium for 3 days. Morphological maturation continued in culture. The rate of incorporation of choline into disaturated phosphatidylcholine and the content of this phospholipid in the explants increased in vitro in a pattern very similar to that which occurs in vivo. The activities of choline kinase and cholinephosphotransferase were also similar in cultured lung and in vivo. Studies of glucose oxidation to CO2 provided additional evidence that the explants remained viable in culture. The explants retained the sensitivity of fetal lung to hormonal action. This was demonstrated by the stimulation of choline incorporation into phospholipid by cyclic AMP and an increase in the glycogen content after exposure to insulin."}
{"id": "PMID:212393", "title": "Rotaviral infections in human neonates.", "content": "Between May 1, 1976 through May 14, 1977, feces from 1,056 five-day-old babies in newborn nurseries were examined by electron microscopy, of which 343 (32.5%) contained rotavirus. Rotaviruses were prevalent throughout the study period, but infection reached its peak during the winter months of December 1976 and January 1977, at which time 46% and 49% of babies, respectively, were excreting rotaviruses. Infection occurred substantially less frequently among breast-fed babies. Further, infected breast-fed babies excreted less virus than those who were bottle fed. Viral particles in feces of breast-fed babies frequently appeared in clumps, which usually contained complete smooth viral particles. Analysis of feeding charts in one of the wards revealed that infection was usually asymptomatic because only 15 of 189 (8%) babies had enteritis. None of these babies had symptoms of sufficient severity to necessitate treatment.", "contents": "Rotaviral infections in human neonates. Between May 1, 1976 through May 14, 1977, feces from 1,056 five-day-old babies in newborn nurseries were examined by electron microscopy, of which 343 (32.5%) contained rotavirus. Rotaviruses were prevalent throughout the study period, but infection reached its peak during the winter months of December 1976 and January 1977, at which time 46% and 49% of babies, respectively, were excreting rotaviruses. Infection occurred substantially less frequently among breast-fed babies. Further, infected breast-fed babies excreted less virus than those who were bottle fed. Viral particles in feces of breast-fed babies frequently appeared in clumps, which usually contained complete smooth viral particles. Analysis of feeding charts in one of the wards revealed that infection was usually asymptomatic because only 15 of 189 (8%) babies had enteritis. None of these babies had symptoms of sufficient severity to necessitate treatment."}
{"id": "PMID:212403", "title": "Economic impact of rotavirus and other neonatal disease agents of animals.", "content": "Methods for estimating the economic impact of disease agents were developed and utilized to assess the relative economic importance of rotavirus and other disease agents in calves. Based on incidence data from 2 sources, Escherichia coli was responsible for the most devastating economic losses (50.9% and 74.6%). Coronaviral (17.5% and 29.7% loss) and rotaviral (3.2% and 9.1% loss) infections ranked 2nd and 3rd, respectively. In one study, cryptosporidial infections (6.5% loss) were estimated to be similar in economic impact to rotaviral infection. Salmonellosis, mycotic gastroenteritis, infectious bovine rhinotracheitis, and bovine viral diarrhea infections accounted for minor losses. The estimated average annual loss of calves for the 7-year period, 1970 through 1976, was $95,500,000/year. Based on data from 2 studies, the estimated average annual loss from E coli was $48.6 and 71.2 million; from coronaviral infection, $16.7 and 28.4 million; from rotaviral infection, $3.1 and $8.7 million; and from cryptosporidial infection, from 1 study, $6.2 million. Estimates of economic impact of disease agents on calves, and likely in other species, indicate that rotaviral infections have a relatively minor role with respect to E coli and coronaviral infections.", "contents": "Economic impact of rotavirus and other neonatal disease agents of animals. Methods for estimating the economic impact of disease agents were developed and utilized to assess the relative economic importance of rotavirus and other disease agents in calves. Based on incidence data from 2 sources, Escherichia coli was responsible for the most devastating economic losses (50.9% and 74.6%). Coronaviral (17.5% and 29.7% loss) and rotaviral (3.2% and 9.1% loss) infections ranked 2nd and 3rd, respectively. In one study, cryptosporidial infections (6.5% loss) were estimated to be similar in economic impact to rotaviral infection. Salmonellosis, mycotic gastroenteritis, infectious bovine rhinotracheitis, and bovine viral diarrhea infections accounted for minor losses. The estimated average annual loss of calves for the 7-year period, 1970 through 1976, was $95,500,000/year. Based on data from 2 studies, the estimated average annual loss from E coli was $48.6 and 71.2 million; from coronaviral infection, $16.7 and 28.4 million; from rotaviral infection, $3.1 and $8.7 million; and from cryptosporidial infection, from 1 study, $6.2 million. Estimates of economic impact of disease agents on calves, and likely in other species, indicate that rotaviral infections have a relatively minor role with respect to E coli and coronaviral infections."}
{"id": "PMID:212404", "title": "Pathogenic relationships of rotavirus, Escherichia coli, and other agents in mixed infections in calves.", "content": "Infection with agents interpreted as causing or contributing to diarrhea (rotavirus, coronavirus, enterotoxigenic Escherichia coli, and cryptosporidia) were demonstrated in 24 of 32 newborn calves that had naturally occurring diarrheal disease. The calves were from 12 herds in Iowa. Infections as well as enteric lesions and hypoglobulinemia occurred more frequently among diarrheal calves than among nondiarrheal calves from these same herds. In most calves, infections were mixed; ie, both viruses, one or both viruses plus cryptosporidia, or rotavirus plus enterotoxigenic E coli.", "contents": "Pathogenic relationships of rotavirus, Escherichia coli, and other agents in mixed infections in calves. Infection with agents interpreted as causing or contributing to diarrhea (rotavirus, coronavirus, enterotoxigenic Escherichia coli, and cryptosporidia) were demonstrated in 24 of 32 newborn calves that had naturally occurring diarrheal disease. The calves were from 12 herds in Iowa. Infections as well as enteric lesions and hypoglobulinemia occurred more frequently among diarrheal calves than among nondiarrheal calves from these same herds. In most calves, infections were mixed; ie, both viruses, one or both viruses plus cryptosporidia, or rotavirus plus enterotoxigenic E coli."}
{"id": "PMID:212408", "title": "Pathophysiologic changes due to coronavirus-induced diarrhea in the calf.", "content": "Extensive water, sodium, chloride, bicarbonate, and potassium losses occur in the diarrheal calf. The water loss is entirely from the extracellular space. In severe cases, hypovolemic shock occurs with the blood volume decreased by as much as one-half. Acidosis, which results from fecal bicarbonate loss, lactic acidosis, and renal dysfunction, results in tissue buffering, which in turn causes the efflux of cellular potassium ions. Although there is a total body potassium deficit, plasma potassium concentration is increased. This, in conjunction with an intracellular deficit, causes weakness, lethargy, and potassium cardiotoxicosis resulting in death. Hypoglycemia also contributes to the weakness and lethargy seem as calves become moribund. These losses from the body and shifts in fluids and electrolytes must be understood to develop the most effective rationale for supportive therapy.", "contents": "Pathophysiologic changes due to coronavirus-induced diarrhea in the calf. Extensive water, sodium, chloride, bicarbonate, and potassium losses occur in the diarrheal calf. The water loss is entirely from the extracellular space. In severe cases, hypovolemic shock occurs with the blood volume decreased by as much as one-half. Acidosis, which results from fecal bicarbonate loss, lactic acidosis, and renal dysfunction, results in tissue buffering, which in turn causes the efflux of cellular potassium ions. Although there is a total body potassium deficit, plasma potassium concentration is increased. This, in conjunction with an intracellular deficit, causes weakness, lethargy, and potassium cardiotoxicosis resulting in death. Hypoglycemia also contributes to the weakness and lethargy seem as calves become moribund. These losses from the body and shifts in fluids and electrolytes must be understood to develop the most effective rationale for supportive therapy."}
{"id": "PMID:212409", "title": "Small plaque variant transmissible gastroenteritis virus.", "content": "A small plaque (SP) variant transmissible gastroenteritis (TGE) virus strain that may be useful in the control of TGE in swine has been developed and tested. This strain was derived from a persistently infected swine leukocyte cell line originally infected with a virulent TGE virus. The SP viral strain was avirulent for 3-day-old susceptible pigs and pregnant gilts. The SP virus elicited protective antibody when inoculated into pregnant gilts oral/intranasally, or intramammarily, or by both of these routes. The morbidity and mortality of their passively immune suckling pigs were 62% and 14%, respectively.", "contents": "Small plaque variant transmissible gastroenteritis virus. A small plaque (SP) variant transmissible gastroenteritis (TGE) virus strain that may be useful in the control of TGE in swine has been developed and tested. This strain was derived from a persistently infected swine leukocyte cell line originally infected with a virulent TGE virus. The SP viral strain was avirulent for 3-day-old susceptible pigs and pregnant gilts. The SP virus elicited protective antibody when inoculated into pregnant gilts oral/intranasally, or intramammarily, or by both of these routes. The morbidity and mortality of their passively immune suckling pigs were 62% and 14%, respectively."}
{"id": "PMID:212415", "title": "Fructose-1,6-biphosphatase of the small intestine. Purification and comparison with liver and muscle fructose-1,6-bisphosphatases.", "content": "The occurrence of specific fructose-1,6-bisphosphatase [D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11] (Fru-1,6-P2ase) in the small intestine was confirmed. 1. Fru-1,6-P2ase was isolated from mouse small intestine by a simple method. The isolated enzyme preparation was an electrophoretically homogeneous protein. 2. The molecular weight and subunit molecular weight were 140,000 and 38,000, respectively. 3. The intestinal enzyme was electrophoretically distinct from the liver enzyme. 4. The kinetic properties of the purified intestinal enzyme were compared with those of the mouse liver and muscle enzymes. 5. Mouse intestinal and muscle Fru-1,6-P2ases hydrolyzed ribulose-1,5-bisphosphate in addition to fructose-1,6-bisphosphate and sedoheptulose-1,7-bisphosphate.", "contents": "Fructose-1,6-biphosphatase of the small intestine. Purification and comparison with liver and muscle fructose-1,6-bisphosphatases. The occurrence of specific fructose-1,6-bisphosphatase [D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11] (Fru-1,6-P2ase) in the small intestine was confirmed. 1. Fru-1,6-P2ase was isolated from mouse small intestine by a simple method. The isolated enzyme preparation was an electrophoretically homogeneous protein. 2. The molecular weight and subunit molecular weight were 140,000 and 38,000, respectively. 3. The intestinal enzyme was electrophoretically distinct from the liver enzyme. 4. The kinetic properties of the purified intestinal enzyme were compared with those of the mouse liver and muscle enzymes. 5. Mouse intestinal and muscle Fru-1,6-P2ases hydrolyzed ribulose-1,5-bisphosphate in addition to fructose-1,6-bisphosphate and sedoheptulose-1,7-bisphosphate."}
{"id": "PMID:212416", "title": "Decrease of rat liver cysteine dioxygenase (cysteine oxidase) activity mediated by glucagon.", "content": "The hepatic cysteine dioxygenase activity of rats was markedly decreased by the intraperitoneal administration of glucagon. The enzyme activity was also decreased by either dibutyryl cyclic AMP or theophylline. The prior administration of actinomycin D completely blocked the glucagon-mediated decrease of enzyme activity, while administrations of this inhibitor of protein synthesis after glucagon injection did not block the decrease of enzyme activity. A single administration of actinomycin D resulted in a slight increase of cysteine dioxygenase activity in the rat liver. On the other hand, the injection of cycloheximide resulted in a rapid decrease of the hepatic cysteine dioxygenase with a half-life of 2.5 h. The half-life of the enzyme in rat liver after glucagon administration was one hour. The administration of hydrocortisone or insulin had no effect on the glucagon-mediated decrease of cysteine dioxygenase of rat liver. The enzyme activity of alloxan diabetic rat liver was almost the same as that of the intact rat liver. The evidence obtained here suggests that enhancement of degradation or inactivation of cysteine dioxygenase is responsible for the glucagon-mediated decrease of the enzyme activity in rat liver.", "contents": "Decrease of rat liver cysteine dioxygenase (cysteine oxidase) activity mediated by glucagon. The hepatic cysteine dioxygenase activity of rats was markedly decreased by the intraperitoneal administration of glucagon. The enzyme activity was also decreased by either dibutyryl cyclic AMP or theophylline. The prior administration of actinomycin D completely blocked the glucagon-mediated decrease of enzyme activity, while administrations of this inhibitor of protein synthesis after glucagon injection did not block the decrease of enzyme activity. A single administration of actinomycin D resulted in a slight increase of cysteine dioxygenase activity in the rat liver. On the other hand, the injection of cycloheximide resulted in a rapid decrease of the hepatic cysteine dioxygenase with a half-life of 2.5 h. The half-life of the enzyme in rat liver after glucagon administration was one hour. The administration of hydrocortisone or insulin had no effect on the glucagon-mediated decrease of cysteine dioxygenase of rat liver. The enzyme activity of alloxan diabetic rat liver was almost the same as that of the intact rat liver. The evidence obtained here suggests that enhancement of degradation or inactivation of cysteine dioxygenase is responsible for the glucagon-mediated decrease of the enzyme activity in rat liver."}
{"id": "PMID:212417", "title": "Genetic evidence that cholera toxin substrates are regulatory components of adenylate cyclase.", "content": "Cholera toxin, using [32P]NAD+ as substrate, specifically radiolabels at least two proteins in plasma membranes of wild type S49 mouse lymphoma cells. The toxin-specific substrates are detectable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis as bands corresponding to molecular weights of 45,000 and a doublet of 52,000 to 53,000. Membranes of two other cell types exhibit similar patterns of radiolabeled bands specifically produced by incubation with cholera toxin: the \"uncoupled\" variant S49 cell, which possesses adenylate cyclase activity unresponsive to hormones, and the HTC4 rat hepatoma cell, which lacks detectable catalytic adenylate cyclase activity but contains components of the cyclase system necessary for regulation by guanyl nucleotides and NaF. Little or no toxin-specific radiolabeling is observed in membranes of a fourth cell type, the adenylate cyclase activity-deficient S49 variant, which functionally lacks components of the cyclase system involved in cholera toxin action and regulation by guanyl nucleotides and NaF. The toxin-specific labeling pattern is not observed in membranes prepared from wild type S49 cells previously treated with cholera toxin in culture. One or both of the toxin substrates thus appears to be involved in regulation of adenylate cyclase by guanyl nucleotides and fluoride ion.", "contents": "Genetic evidence that cholera toxin substrates are regulatory components of adenylate cyclase. Cholera toxin, using [32P]NAD+ as substrate, specifically radiolabels at least two proteins in plasma membranes of wild type S49 mouse lymphoma cells. The toxin-specific substrates are detectable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis as bands corresponding to molecular weights of 45,000 and a doublet of 52,000 to 53,000. Membranes of two other cell types exhibit similar patterns of radiolabeled bands specifically produced by incubation with cholera toxin: the \"uncoupled\" variant S49 cell, which possesses adenylate cyclase activity unresponsive to hormones, and the HTC4 rat hepatoma cell, which lacks detectable catalytic adenylate cyclase activity but contains components of the cyclase system necessary for regulation by guanyl nucleotides and NaF. Little or no toxin-specific radiolabeling is observed in membranes of a fourth cell type, the adenylate cyclase activity-deficient S49 variant, which functionally lacks components of the cyclase system involved in cholera toxin action and regulation by guanyl nucleotides and NaF. The toxin-specific labeling pattern is not observed in membranes prepared from wild type S49 cells previously treated with cholera toxin in culture. One or both of the toxin substrates thus appears to be involved in regulation of adenylate cyclase by guanyl nucleotides and fluoride ion."}
{"id": "PMID:212418", "title": "Autophosphorylation of rabbit skeletal muscle cyclic AMP-dependent protein kinase I catalytic subunit.", "content": "The catalytic subunit of rabbit skeletal muscle cyclic AMP-dependent protein kinase I can catalyze self-phosphorylation. The autophosphorylation reaction uses ATP as the phosphoryl donor, requires Mg2+, and is inhibited by polyarginine. Prior treatment of the catalytic subunit with Escherichia coli alkaline phosphatase in the presence of bovine serum albumin greatly enhances the autophosphorylation of the subunit. The protein-bound phosphate is stable in acid but labile in base. Incubation of the 32P-labeled phosphoenzyme with histones led neither to the phosphorylation of histones nor to a loss of radioactivity from the phosphoenzyme. The results suggest that the phosphoenzyme does not represent an intermediate of the phosphotransferase reaction.", "contents": "Autophosphorylation of rabbit skeletal muscle cyclic AMP-dependent protein kinase I catalytic subunit. The catalytic subunit of rabbit skeletal muscle cyclic AMP-dependent protein kinase I can catalyze self-phosphorylation. The autophosphorylation reaction uses ATP as the phosphoryl donor, requires Mg2+, and is inhibited by polyarginine. Prior treatment of the catalytic subunit with Escherichia coli alkaline phosphatase in the presence of bovine serum albumin greatly enhances the autophosphorylation of the subunit. The protein-bound phosphate is stable in acid but labile in base. Incubation of the 32P-labeled phosphoenzyme with histones led neither to the phosphorylation of histones nor to a loss of radioactivity from the phosphoenzyme. The results suggest that the phosphoenzyme does not represent an intermediate of the phosphotransferase reaction."}
{"id": "PMID:212419", "title": "Characteristics of lead ion-stimulated phosphorylation of Electrophorus electricus electroplax (Na+ + K+)-adenosine triphosphatase and inhibition of ATP-ADP exchange.", "content": "Pb2+-stimulated phosphorylation of Electrophorus electricus electroplax (Na+ + K+)-adenosine triphosphatase is prevented by stoichiometric quantities of 2,3-dimercaptopropanol. The chelator in the same low concentrations does not block Na+-dependent phosphorylation. Both Pb2+-and Na+-dependent phosphorylation reactions show the same dependence on MgCl2. Phosphorylation in the presence of both Na+ and Pb2+ is cumulative suggesting that Pb2+ and Na+ bind at separate, independent sites. The enthalpy change due to binding of Pb2+ is about -1.76 kcal/mol. 32P-phosphopeptides obtained from pronase or pepsin digests of Pb2+-and Na+-dependent phosphoproteins are electrophoretically identical. Pb2+ does not stimulate but does inhibit ATP-ADP exchange activity under the conditions in which this activity is stimulated by Na+. Since the phosphorylation sites are identical, it is concluded that the differences in reactivity of the Na+- and Pb2+-phosphoenzymes are due to different conformational changes produced by binding of Na+ and Pb2+. The Pb2+-sensitive conformation is critical for Na+ specificity of phosphorylation, reversibility of phosphorylation, and for phosphatase activity but not for acceptor site phosphorylation by ATP. These findings have implications for enzyme reaction models.", "contents": "Characteristics of lead ion-stimulated phosphorylation of Electrophorus electricus electroplax (Na+ + K+)-adenosine triphosphatase and inhibition of ATP-ADP exchange. Pb2+-stimulated phosphorylation of Electrophorus electricus electroplax (Na+ + K+)-adenosine triphosphatase is prevented by stoichiometric quantities of 2,3-dimercaptopropanol. The chelator in the same low concentrations does not block Na+-dependent phosphorylation. Both Pb2+-and Na+-dependent phosphorylation reactions show the same dependence on MgCl2. Phosphorylation in the presence of both Na+ and Pb2+ is cumulative suggesting that Pb2+ and Na+ bind at separate, independent sites. The enthalpy change due to binding of Pb2+ is about -1.76 kcal/mol. 32P-phosphopeptides obtained from pronase or pepsin digests of Pb2+-and Na+-dependent phosphoproteins are electrophoretically identical. Pb2+ does not stimulate but does inhibit ATP-ADP exchange activity under the conditions in which this activity is stimulated by Na+. Since the phosphorylation sites are identical, it is concluded that the differences in reactivity of the Na+- and Pb2+-phosphoenzymes are due to different conformational changes produced by binding of Na+ and Pb2+. The Pb2+-sensitive conformation is critical for Na+ specificity of phosphorylation, reversibility of phosphorylation, and for phosphatase activity but not for acceptor site phosphorylation by ATP. These findings have implications for enzyme reaction models."}
{"id": "PMID:212421", "title": "Stimulation and inhibition of the protein synthetic process by NAD+ in lysed rabbit reticulocytes.", "content": "NAD+ at 0.16 mM stimulates the initiation step of the protein synthetic process in lysed rabbit reticulocytes. This conclusion is based on the stimulation of (i) the transfer of formylmethionine from f[35S]Met-tRNAfMet into polypeptide, (ii) the accumulation of the initial dipeptide, methionylvaline, in the presence of pactamycin, and (iii) the formation of the 40 S initiation complex. The effect of NAD+ changes from a stimulatory role on protein synthesis to an inhibitory role at concentrations greater than 0.16 mM. At 4.0 mM NAD+, protein synthesis is inhibited. This has been demonstrated experimentally by using the same three assays described above. In addition, 4.0 mM NAD+ inhibits MettRNAfMet.initiation factor.GTP ternary complex formation. The elongation and termination steps of polypeptide synthesis are not affected by 0.16 to 4.0 mM NAD+. The data presented clearly show that the stimulatory activity of 0.16 mM NAD+ and the inhibitory activity of 4.0 mM NAD+ affects the initiation step of the protein synthetic process in lysed rabbit reticulocytes.", "contents": "Stimulation and inhibition of the protein synthetic process by NAD+ in lysed rabbit reticulocytes. NAD+ at 0.16 mM stimulates the initiation step of the protein synthetic process in lysed rabbit reticulocytes. This conclusion is based on the stimulation of (i) the transfer of formylmethionine from f[35S]Met-tRNAfMet into polypeptide, (ii) the accumulation of the initial dipeptide, methionylvaline, in the presence of pactamycin, and (iii) the formation of the 40 S initiation complex. The effect of NAD+ changes from a stimulatory role on protein synthesis to an inhibitory role at concentrations greater than 0.16 mM. At 4.0 mM NAD+, protein synthesis is inhibited. This has been demonstrated experimentally by using the same three assays described above. In addition, 4.0 mM NAD+ inhibits MettRNAfMet.initiation factor.GTP ternary complex formation. The elongation and termination steps of polypeptide synthesis are not affected by 0.16 to 4.0 mM NAD+. The data presented clearly show that the stimulatory activity of 0.16 mM NAD+ and the inhibitory activity of 4.0 mM NAD+ affects the initiation step of the protein synthetic process in lysed rabbit reticulocytes."}
{"id": "PMID:212423", "title": "Inactivation of phosphorylase phosphatase by a factor from rabbit liver and its chemical characterization as glutathione disulfide.", "content": "A factor inactivating phosphorylase phosphatase was isolated from rabbit liver. The isolation procedure consisted of heat treatment at 85 degrees C, extraction with n-butyl alcohol, and chromatography on Dowex 1 and DEAE-cellulose columns. The purified factor was different from the known protein inhibitors and was shown to be tripeptide composed of equimolar amounts of glutamic acid, cysteine, and glycine. The NH2-terminal and COOH-terminal amino acids were determined as glutamic acid and glycine, respectively. The factor was finally identified as glutathione disulfide by high voltage paper electrophoresis, paper chromatography, and liquid column chromatography using an amino acid analyzer. Addition of the purified factor or glutathione disulfide converted phosphorylase phosphatase to a stable, less active enzyme species, the extent of conversion depending on the amount added. The inactivated phosphatase was completely reactivated by addition of both glutathione (or 2-mercaptoethanol) and Mn2+ and partially reactivated by adding glutathione alone. Injection of glutathione disulfide into the portal vein of rabbits caused a rapid increase in phosphorylase alpha activity in the liver. These results suggest that glutathione disulfide is involved in regulation of phosphorylase activity in vivo, by causing inactivation of phosphorylase phosphatase in the liver.", "contents": "Inactivation of phosphorylase phosphatase by a factor from rabbit liver and its chemical characterization as glutathione disulfide. A factor inactivating phosphorylase phosphatase was isolated from rabbit liver. The isolation procedure consisted of heat treatment at 85 degrees C, extraction with n-butyl alcohol, and chromatography on Dowex 1 and DEAE-cellulose columns. The purified factor was different from the known protein inhibitors and was shown to be tripeptide composed of equimolar amounts of glutamic acid, cysteine, and glycine. The NH2-terminal and COOH-terminal amino acids were determined as glutamic acid and glycine, respectively. The factor was finally identified as glutathione disulfide by high voltage paper electrophoresis, paper chromatography, and liquid column chromatography using an amino acid analyzer. Addition of the purified factor or glutathione disulfide converted phosphorylase phosphatase to a stable, less active enzyme species, the extent of conversion depending on the amount added. The inactivated phosphatase was completely reactivated by addition of both glutathione (or 2-mercaptoethanol) and Mn2+ and partially reactivated by adding glutathione alone. Injection of glutathione disulfide into the portal vein of rabbits caused a rapid increase in phosphorylase alpha activity in the liver. These results suggest that glutathione disulfide is involved in regulation of phosphorylase activity in vivo, by causing inactivation of phosphorylase phosphatase in the liver."}
{"id": "PMID:212432", "title": "A novel phosphodiesterase from Aspergillus niger and its application to the study of membrane-derived oligosaccharides and other glycerol-containing biopolymers.", "content": "A novel phosphodiesterase has been found in commercially available extracts of Aspergillus niger and has been partially purified by fractionation with acetone and chromatography on carboxymethylcellulose. The enzyme attacks glycerophosphodiester bonds with the liberation of free glycerol only. The synthetic substrate glucose 6-phospho-sn-1'(3')-glycerol is hydrolyzed with production of equivalent amounts of free glycerol and glucose 6-phosphate. Similarly, the enzymic hydrolysis of sn-glycero-3-phosphocholine liberates glycerol and phosphocholine. The hydrophilic head groups of membrane phospholipids of Escherichia coli are continuously transferred to a closely related family of oligosaccharides (\"membrane-derived oligosaccharides\") containing glucose as the sole sugar (van Golde, L. M. G., Schulman, H., and Kennedy, E. P. (1973) Proc. Natl. Acad. Sci. U. S. A. 70, 1368--1372). Oligosaccharide A-2 contains sn-1-glycerophosphate residues (derived from phosphatidylglycerol) in phosphodiester linkage. Treatment of this oligosaccharide with the phosphodiesterase led to the liberation of nearly all of the glycerol as free glycerol. Subsequent partial acid hydrolysis of the enzyme-treated oligosaccharide led to the recovery of glucose 6-phosphate in almost quantitative yield. The sn-1-glycerophosphate residues are therefore linked to position 6 of glucose units of the oligosaccharide. The activity of the enzyme is not restricted to glycerophosphodiesterases since it will hydrolyze phosphodiesters containing other polyols such as the synthetically prepared glucose 6-phospho-DL-1'(2'-hydroxy-3'-ethoxy)propane.", "contents": "A novel phosphodiesterase from Aspergillus niger and its application to the study of membrane-derived oligosaccharides and other glycerol-containing biopolymers. A novel phosphodiesterase has been found in commercially available extracts of Aspergillus niger and has been partially purified by fractionation with acetone and chromatography on carboxymethylcellulose. The enzyme attacks glycerophosphodiester bonds with the liberation of free glycerol only. The synthetic substrate glucose 6-phospho-sn-1'(3')-glycerol is hydrolyzed with production of equivalent amounts of free glycerol and glucose 6-phosphate. Similarly, the enzymic hydrolysis of sn-glycero-3-phosphocholine liberates glycerol and phosphocholine. The hydrophilic head groups of membrane phospholipids of Escherichia coli are continuously transferred to a closely related family of oligosaccharides (\"membrane-derived oligosaccharides\") containing glucose as the sole sugar (van Golde, L. M. G., Schulman, H., and Kennedy, E. P. (1973) Proc. Natl. Acad. Sci. U. S. A. 70, 1368--1372). Oligosaccharide A-2 contains sn-1-glycerophosphate residues (derived from phosphatidylglycerol) in phosphodiester linkage. Treatment of this oligosaccharide with the phosphodiesterase led to the liberation of nearly all of the glycerol as free glycerol. Subsequent partial acid hydrolysis of the enzyme-treated oligosaccharide led to the recovery of glucose 6-phosphate in almost quantitative yield. The sn-1-glycerophosphate residues are therefore linked to position 6 of glucose units of the oligosaccharide. The activity of the enzyme is not restricted to glycerophosphodiesterases since it will hydrolyze phosphodiesters containing other polyols such as the synthetically prepared glucose 6-phospho-DL-1'(2'-hydroxy-3'-ethoxy)propane."}
{"id": "PMID:212433", "title": "Photoreduction of copper chromophores in blue oxidases.", "content": "The low temperature (77 K) irradiation of oxidized ceruloplasmin and Rhus vernicifera laccase at the 330 nm absorption which arises from type 3 copper leads to the reduction of type 1 copper as demonstrated by bleaching of the 610 nm chromophore and the decrease of the EPR signal associated with this species. Type 2 copper remains unaffected. Concomitant with the type 1 copper reduction, a new EPR signal which is possibly that of a biradical appears. Upon thawing, type 1 copper is reversibly oxidized and the radical signal disappears. Irradiation of oxidized protein at the absorption band of type 1 copper produces no spectral change. An EPR study at room temperature confirms the wave-length specificity and reversibility of the photoreduction of type 1 copper and radical formation. Radical appearance and disappearance at room temperature are extremely slow (tau1/2 approximately 30 min). Optical studies at room temperature show that upon anaerobic irradiation of laccase in the 330 nm absorption band, both type 3 and type 1 chromophores are slowly reduced. Upon return to the dark and in the presence of O2, both type 3 and type 1 centers are reoxidized. Oxidizing equivalents either from O2 or K3Fe(CN)6 are required for the reoxidation reaction. These studies demonstrate that there is a direct energy transfer between type 3 and type 1 copper sites in blue copper oxidases.", "contents": "Photoreduction of copper chromophores in blue oxidases. The low temperature (77 K) irradiation of oxidized ceruloplasmin and Rhus vernicifera laccase at the 330 nm absorption which arises from type 3 copper leads to the reduction of type 1 copper as demonstrated by bleaching of the 610 nm chromophore and the decrease of the EPR signal associated with this species. Type 2 copper remains unaffected. Concomitant with the type 1 copper reduction, a new EPR signal which is possibly that of a biradical appears. Upon thawing, type 1 copper is reversibly oxidized and the radical signal disappears. Irradiation of oxidized protein at the absorption band of type 1 copper produces no spectral change. An EPR study at room temperature confirms the wave-length specificity and reversibility of the photoreduction of type 1 copper and radical formation. Radical appearance and disappearance at room temperature are extremely slow (tau1/2 approximately 30 min). Optical studies at room temperature show that upon anaerobic irradiation of laccase in the 330 nm absorption band, both type 3 and type 1 chromophores are slowly reduced. Upon return to the dark and in the presence of O2, both type 3 and type 1 centers are reoxidized. Oxidizing equivalents either from O2 or K3Fe(CN)6 are required for the reoxidation reaction. These studies demonstrate that there is a direct energy transfer between type 3 and type 1 copper sites in blue copper oxidases."}
{"id": "PMID:212434", "title": "The synthesis of complex-type oligosaccharides. I. Structure of the lipid-linked oligosaccharide precursor of the complex-type oligosaccharides of the vesicular stomatitis virus G protein.", "content": "The synthesis of the complex-type oligosaccharide unit of the vesicular stomatitis virus G protein is initiated by the en bloc transfer of a high molecular weight oligosaccharide from a lipid carrier to the nascent polypeptide. Following transfer the oligosaccharide is \"processed\" by removal of glucose and mannose residues and the sugars that constitute the outer branches of the complex-type oligosaccharide are added. The structure of the oligosaccharide moiety of the lipid-linked precursor has been elucidated in order to further define the steps involved in processing. Since it was not feasible to obtain adequate amounts of material for standard structural studies, most of the structural studies were performed on radiolabeled material, with radioactivity incorporated differentially into glucose, mannose, and N-acetylglucosamine. Based on endo-beta-N-acetylglucosaminidase CII digestion, alpha-mannosidase digestion, acetolysis, Smith periodate degradation, methylation analysis, and periodate oxidation, we propose the following structure for the oligosaccharide moiety of the lipid-linked oligosaccharide.", "contents": "The synthesis of complex-type oligosaccharides. I. Structure of the lipid-linked oligosaccharide precursor of the complex-type oligosaccharides of the vesicular stomatitis virus G protein. The synthesis of the complex-type oligosaccharide unit of the vesicular stomatitis virus G protein is initiated by the en bloc transfer of a high molecular weight oligosaccharide from a lipid carrier to the nascent polypeptide. Following transfer the oligosaccharide is \"processed\" by removal of glucose and mannose residues and the sugars that constitute the outer branches of the complex-type oligosaccharide are added. The structure of the oligosaccharide moiety of the lipid-linked precursor has been elucidated in order to further define the steps involved in processing. Since it was not feasible to obtain adequate amounts of material for standard structural studies, most of the structural studies were performed on radiolabeled material, with radioactivity incorporated differentially into glucose, mannose, and N-acetylglucosamine. Based on endo-beta-N-acetylglucosaminidase CII digestion, alpha-mannosidase digestion, acetolysis, Smith periodate degradation, methylation analysis, and periodate oxidation, we propose the following structure for the oligosaccharide moiety of the lipid-linked oligosaccharide."}
{"id": "PMID:212438", "title": "Inhibition of the degradation of receptor-bound human choriogonadotropin by lysosomotropic agents, protease inhibitors, and metabolic inhibitors.", "content": "A previous report from this laboratory showed that binding of iodine-labeled human choriogonadotropin to Leydig tumor cells is not a reversible process (Ascoli, M., and Puett, D. (1978) J. Biol. Chem. 253, 4892--4899). Most of the cell-bound hormone was found to be degraded to 3'-monoiodotyrosine before being released from the cells, and the degradation process could be inhibited by the lysosomotropic agents NH4Cl, chloroquine, and Triton WR-1339. It is reported herein that the degradation of receptor-bound human choriogonadotropin is an energy-dependent process, which can be inhibited by compounds that interfere with glycolysis or oxidative phosphorylation (e.g. NaF, NaN3, NaCN, and 2-deoxyglucose). Hormone degradation is also inhibited by some protease inhibitors such as the chloromethyl ketones of lysine and phenylalanine, but not by specific trypsin inhibitors (e.g. p-aminobenzamidine and p-tosyl-L-arginine methyl ester). With the exception of NH4Cl, it was found that the compounds which inhibit hormone degradation also inhibit hormone-stimulated steroidogenesis. However, the present results involving dose dependency, and those given in the following paper (Ascoli, M. (1978) J. Biol. Chem. 253, 7839--7843), indicate that these two phenomena are not related.", "contents": "Inhibition of the degradation of receptor-bound human choriogonadotropin by lysosomotropic agents, protease inhibitors, and metabolic inhibitors. A previous report from this laboratory showed that binding of iodine-labeled human choriogonadotropin to Leydig tumor cells is not a reversible process (Ascoli, M., and Puett, D. (1978) J. Biol. Chem. 253, 4892--4899). Most of the cell-bound hormone was found to be degraded to 3'-monoiodotyrosine before being released from the cells, and the degradation process could be inhibited by the lysosomotropic agents NH4Cl, chloroquine, and Triton WR-1339. It is reported herein that the degradation of receptor-bound human choriogonadotropin is an energy-dependent process, which can be inhibited by compounds that interfere with glycolysis or oxidative phosphorylation (e.g. NaF, NaN3, NaCN, and 2-deoxyglucose). Hormone degradation is also inhibited by some protease inhibitors such as the chloromethyl ketones of lysine and phenylalanine, but not by specific trypsin inhibitors (e.g. p-aminobenzamidine and p-tosyl-L-arginine methyl ester). With the exception of NH4Cl, it was found that the compounds which inhibit hormone degradation also inhibit hormone-stimulated steroidogenesis. However, the present results involving dose dependency, and those given in the following paper (Ascoli, M. (1978) J. Biol. Chem. 253, 7839--7843), indicate that these two phenomena are not related."}
{"id": "PMID:212439", "title": "Demonstration of a direct effect of inhibitors of the degradation of receptor-bound human choriogonadotropin on the steroidogenic pathway.", "content": "Results presented in the previous paper (Ascoli, M., and Puett, D. (1978) J. Biol. Chem. 253, 7832--7838) show that the degradation of receptor-bound 125I-labeled human choriogonadotropin can be inhibited by chloroquine, protease inhibitors, and metabolic inhibitors. These compounds were also shown to inhibit gonadotropin-stimulated steroidogenesis. It is reported herein that these inhibitors also block the stimulation of steroidogenesis by both cholera toxin and 8-Br-adenosine 3':5'-monophosphate, thus showing that they are not specific for the hormonal stimuli. These results, taken together with previous observations that show that NH2Cl can block hormone degradation without inhibiting hormone-stimulated steroidogenesis, strongly suggest that the degradation of choriogonadotropin is not required for its stimulatory action on progesterone production.", "contents": "Demonstration of a direct effect of inhibitors of the degradation of receptor-bound human choriogonadotropin on the steroidogenic pathway. Results presented in the previous paper (Ascoli, M., and Puett, D. (1978) J. Biol. Chem. 253, 7832--7838) show that the degradation of receptor-bound 125I-labeled human choriogonadotropin can be inhibited by chloroquine, protease inhibitors, and metabolic inhibitors. These compounds were also shown to inhibit gonadotropin-stimulated steroidogenesis. It is reported herein that these inhibitors also block the stimulation of steroidogenesis by both cholera toxin and 8-Br-adenosine 3':5'-monophosphate, thus showing that they are not specific for the hormonal stimuli. These results, taken together with previous observations that show that NH2Cl can block hormone degradation without inhibiting hormone-stimulated steroidogenesis, strongly suggest that the degradation of choriogonadotropin is not required for its stimulatory action on progesterone production."}
{"id": "PMID:212441", "title": "Reconstitution of escherichia coli succinoxidase from soluble components.", "content": "1. The membrane-bound succinoxidase of Escherichia coli was fractionated with deoxycholate into three soluble components, viz. succinate dehydrogenase.cytochrome b1 complex, cytochrome oxidase complex, and a factor identified as a phospholipid-containing component. 2. The dehydrogenase and cytochrome oxidase complexes were partially purified by filtration on Amicon membranes, Sepharose 4B chromatography, and sucrose gradient centrifugation. 3. Reconstitution of membranous succinoxidase, which catalyzes the oxidation of succinate by molecular oxygen by an integrated CN(-)-sensitive pathway, was achieved by mixing the soluble succinate dehydrogenase.cytochrome b1 complex with the soluble cytochrome oxidase complex in the presence of deoxycholate and then removing the detergent by gel filtration on Sephadex G-75. The phospholipid-containing factor stimulated the formation of succinoxidase by about 100% over that observed with the two complexes. 4. Isopycnic sucrose gradient centrifugation of succinate dehydrogenase.cytochrome b1 complex, cytochrome oxidase, and the reconstituted succinoxidase gave buoyant densities (p value) as 1.167, 1.229, and 1.194, respectively. 5. Electron microscopic evidence is presented for the vesicular nature of the reconstituted succinoxidase.", "contents": "Reconstitution of escherichia coli succinoxidase from soluble components. 1. The membrane-bound succinoxidase of Escherichia coli was fractionated with deoxycholate into three soluble components, viz. succinate dehydrogenase.cytochrome b1 complex, cytochrome oxidase complex, and a factor identified as a phospholipid-containing component. 2. The dehydrogenase and cytochrome oxidase complexes were partially purified by filtration on Amicon membranes, Sepharose 4B chromatography, and sucrose gradient centrifugation. 3. Reconstitution of membranous succinoxidase, which catalyzes the oxidation of succinate by molecular oxygen by an integrated CN(-)-sensitive pathway, was achieved by mixing the soluble succinate dehydrogenase.cytochrome b1 complex with the soluble cytochrome oxidase complex in the presence of deoxycholate and then removing the detergent by gel filtration on Sephadex G-75. The phospholipid-containing factor stimulated the formation of succinoxidase by about 100% over that observed with the two complexes. 4. Isopycnic sucrose gradient centrifugation of succinate dehydrogenase.cytochrome b1 complex, cytochrome oxidase, and the reconstituted succinoxidase gave buoyant densities (p value) as 1.167, 1.229, and 1.194, respectively. 5. Electron microscopic evidence is presented for the vesicular nature of the reconstituted succinoxidase."}
{"id": "PMID:212443", "title": "Bone changes induced by diphenylhydantoin in chicks on a controlled vitamin D intake.", "content": "Florid rickets developed in chicks receiving doses of diphenylhydantoin analogous to doses used in humans as anticonvulsants, vitamin D3 being given in amounts sufficient for normal bone mineralization in controls. The changes in the bones were directly related to the dose of diphenylhydantoin and inversely related to the dose of vitamin D3. Bone mineralization was assessed by roentgenography, histological examination, microradiography, and measurement of bone ash. Of these methods, roentgenography was the least sensitive. Rachitic changes were detectable by light microscopy and microradiography in chicks whose skeletons appeared normal roentgenographically. Roentgenographic evidence of rickets became detectable only when the rickets was far advanced. Rickets developed at serum levels of diphenylhydantoin similar to those found in patients taking anticonvulsant medication.", "contents": "Bone changes induced by diphenylhydantoin in chicks on a controlled vitamin D intake. Florid rickets developed in chicks receiving doses of diphenylhydantoin analogous to doses used in humans as anticonvulsants, vitamin D3 being given in amounts sufficient for normal bone mineralization in controls. The changes in the bones were directly related to the dose of diphenylhydantoin and inversely related to the dose of vitamin D3. Bone mineralization was assessed by roentgenography, histological examination, microradiography, and measurement of bone ash. Of these methods, roentgenography was the least sensitive. Rachitic changes were detectable by light microscopy and microradiography in chicks whose skeletons appeared normal roentgenographically. Roentgenographic evidence of rickets became detectable only when the rickets was far advanced. Rickets developed at serum levels of diphenylhydantoin similar to those found in patients taking anticonvulsant medication."}
{"id": "PMID:212444", "title": "Quantitative high-performance thin-layer chromatography of lipids in plasma and liver homogenates after direct application of 0.5-microliter samples to the silica-gel layer.", "content": "Lipid profiles were determined by high-performance thin-layer chromatography (HPTLC) after direct application of 0.5 microliter plasma from capillary blood to the silica-gel layer. Coefficients of variation for the fluorescence measurements were 2.1% for phosphatidylcholine. The recovery of known amounts of lipid was 96--100%. A linear relationship between peak area and amount of lipid was found in the nmole range, corresponding to the amount of lipid in 0.125--0.75 microliter Lipid-Trol, which served as the standard reference sample. The plasma lipids of healthy subjects and of patients suffering from various illnesses were analyzed using reference methods and HPTLC. Identical values were obtained for cholesterol esters, triacylglycerols and phosphatidylcholine. Free cholesterol values determined by HPTLC were slightly lower (7%). The correlation between data obtained by reference methods and HPTLC was as follows: cholesterol, r = 0.938; cholesterol esters, r = 0.964; triacylglycerols, r = 0.985; phosphatidylcholine, r = 0.938. The separaiton and quantitation of liver lipids using HPTLC after direct application of the tissue homogenate to the silical-gel layer was carried out. Comparison with reference methods revealed that HPTLC gave higher cholesterol values (24%). The triacylglycerol concentrations, however, were identical under both methods and correalted satisfactorily (r = 0.959).", "contents": "Quantitative high-performance thin-layer chromatography of lipids in plasma and liver homogenates after direct application of 0.5-microliter samples to the silica-gel layer. Lipid profiles were determined by high-performance thin-layer chromatography (HPTLC) after direct application of 0.5 microliter plasma from capillary blood to the silica-gel layer. Coefficients of variation for the fluorescence measurements were 2.1% for phosphatidylcholine. The recovery of known amounts of lipid was 96--100%. A linear relationship between peak area and amount of lipid was found in the nmole range, corresponding to the amount of lipid in 0.125--0.75 microliter Lipid-Trol, which served as the standard reference sample. The plasma lipids of healthy subjects and of patients suffering from various illnesses were analyzed using reference methods and HPTLC. Identical values were obtained for cholesterol esters, triacylglycerols and phosphatidylcholine. Free cholesterol values determined by HPTLC were slightly lower (7%). The correlation between data obtained by reference methods and HPTLC was as follows: cholesterol, r = 0.938; cholesterol esters, r = 0.964; triacylglycerols, r = 0.985; phosphatidylcholine, r = 0.938. The separaiton and quantitation of liver lipids using HPTLC after direct application of the tissue homogenate to the silical-gel layer was carried out. Comparison with reference methods revealed that HPTLC gave higher cholesterol values (24%). The triacylglycerol concentrations, however, were identical under both methods and correalted satisfactorily (r = 0.959)."}
{"id": "PMID:212446", "title": "Analysis of antibody assay methods and classes of viral antibodies in serodiagnosis of cytomegalovirus infection.", "content": "Forty-nine serum pairs with antibody to cytomegalovirus (CMV) were evaluated for rises in antibody titer (greater than or equal to fourfold) by indirect hemagglutination (IHA) and complement fixation (CF), using a freeze-thaw antigen (FT) and a glycine extract antigen (GE). In this sample CF-FT detected more rises in antibody titer than did CF-GE. IHA detected the least number. The apparent reason for stationary antibody titers with CF-GE and IHA was the presence of high antibody titers in the first serum specimen. Separation of immunoglobulin classes of 20 serum pairs by sucrose gradient centrifugation indicated that these antibodies with IHA were of the immunoglobulin M (IgM) class and those with CF-GE were of the IgG class. By separation of immunoglobulin classes, rises in IgG CMV antibody titers were seen with IHA, rises not observed in the whole serum because of high IgM antibody titers in the first serum specimen. Absence of rises in antibody titers with CF-FT was due in part to too early sampling of the second serum specimen (less than 21 days) and in part to an apparent inability of some individuals to respond with antibody reactive with FT antigen. CF-GE and CF-FT antibodies of the IgM class were detected in some sera, usually in specimens collected more than 10 days after the onset of symptoms. Although reactive with CMV antigen, the specificity of these IgM antibodies in relation to rheumatoid factor requires clarification.", "contents": "Analysis of antibody assay methods and classes of viral antibodies in serodiagnosis of cytomegalovirus infection. Forty-nine serum pairs with antibody to cytomegalovirus (CMV) were evaluated for rises in antibody titer (greater than or equal to fourfold) by indirect hemagglutination (IHA) and complement fixation (CF), using a freeze-thaw antigen (FT) and a glycine extract antigen (GE). In this sample CF-FT detected more rises in antibody titer than did CF-GE. IHA detected the least number. The apparent reason for stationary antibody titers with CF-GE and IHA was the presence of high antibody titers in the first serum specimen. Separation of immunoglobulin classes of 20 serum pairs by sucrose gradient centrifugation indicated that these antibodies with IHA were of the immunoglobulin M (IgM) class and those with CF-GE were of the IgG class. By separation of immunoglobulin classes, rises in IgG CMV antibody titers were seen with IHA, rises not observed in the whole serum because of high IgM antibody titers in the first serum specimen. Absence of rises in antibody titers with CF-FT was due in part to too early sampling of the second serum specimen (less than 21 days) and in part to an apparent inability of some individuals to respond with antibody reactive with FT antigen. CF-GE and CF-FT antibodies of the IgM class were detected in some sera, usually in specimens collected more than 10 days after the onset of symptoms. Although reactive with CMV antigen, the specificity of these IgM antibodies in relation to rheumatoid factor requires clarification."}
{"id": "PMID:212447", "title": "Role of rheumatoid factor in complement fixation and indirect hemagglutination tests for immunoglobulin M antibody to cytomegalovirus.", "content": "Absorption of immunoglobulin M (IgM)-rheumatoid factor (RF) from serum samples by reaction with insolubilized gamma globulin reduced the complement-fixing (CF) antibody titer to cytomegalovirus (CMV) antigen to less than 1:2 in the IgM fraction of some, but not all, sera. Thus, IgM-CF activity in some sera appeared to be due to specific IgM anti-CMV antibody and in other sera to complexes of IgM-RF with antiviral IgG antibody. Prozones were present in the CF tests on IgM fractions. Increasing the concentration of antigen from 2 to 4 U reduced the prozone titer by one or two double dilutions. This observation suggested that a competition for antigen may be operating at low dilutions of IgM antibody fractions. Removal of RF had little or no effect on the reaction of the IgM fraction of sera with CMV by the indirect hemagglutination test.", "contents": "Role of rheumatoid factor in complement fixation and indirect hemagglutination tests for immunoglobulin M antibody to cytomegalovirus. Absorption of immunoglobulin M (IgM)-rheumatoid factor (RF) from serum samples by reaction with insolubilized gamma globulin reduced the complement-fixing (CF) antibody titer to cytomegalovirus (CMV) antigen to less than 1:2 in the IgM fraction of some, but not all, sera. Thus, IgM-CF activity in some sera appeared to be due to specific IgM anti-CMV antibody and in other sera to complexes of IgM-RF with antiviral IgG antibody. Prozones were present in the CF tests on IgM fractions. Increasing the concentration of antigen from 2 to 4 U reduced the prozone titer by one or two double dilutions. This observation suggested that a competition for antigen may be operating at low dilutions of IgM antibody fractions. Removal of RF had little or no effect on the reaction of the IgM fraction of sera with CMV by the indirect hemagglutination test."}
{"id": "PMID:212448", "title": "Rickettsial indirect hemagglutination test: isolation of erythrocyte-sensitizing substance.", "content": "The erythrocyte-sensitizing substances (ESS) of Rickettsia prowazekii and R. conorii were characterized by biological and chemical criteria. ESS could be derived from either soluble or particulate complement-fixing antigens obtained by ether extraction of rickettsiae. The soluble complement-fixing antigen exhibited two peaks of serological activity in potassium tartrate density gradients. The particulate complement-fixing antigen coincided with the more dense peak but was distinguishable by its sedimentation in rate-zonal sucrose gradients. ESS was obtained from each of the complement-fixing-reactive gradient peaks by extraction with hot alkali and was quantified by a modified indirect hemagglutination test. These ESS preparations sedimented similarly in potassium tartrate gradients and were shown to contain protein and carbohydrate, both by colorimetric tests and by incorporation of radioactive precursors. The serological activity of ESS was unaffected by trypsin, but both antigenicity and erythrocyte-binding capacity were reduced after exposure to sodium metaperiodate. Highly purified ESS was rapidly inactivated by potassium tartrate and required stabilization with bovine plasma albumin.", "contents": "Rickettsial indirect hemagglutination test: isolation of erythrocyte-sensitizing substance. The erythrocyte-sensitizing substances (ESS) of Rickettsia prowazekii and R. conorii were characterized by biological and chemical criteria. ESS could be derived from either soluble or particulate complement-fixing antigens obtained by ether extraction of rickettsiae. The soluble complement-fixing antigen exhibited two peaks of serological activity in potassium tartrate density gradients. The particulate complement-fixing antigen coincided with the more dense peak but was distinguishable by its sedimentation in rate-zonal sucrose gradients. ESS was obtained from each of the complement-fixing-reactive gradient peaks by extraction with hot alkali and was quantified by a modified indirect hemagglutination test. These ESS preparations sedimented similarly in potassium tartrate gradients and were shown to contain protein and carbohydrate, both by colorimetric tests and by incorporation of radioactive precursors. The serological activity of ESS was unaffected by trypsin, but both antigenicity and erythrocyte-binding capacity were reduced after exposure to sodium metaperiodate. Highly purified ESS was rapidly inactivated by potassium tartrate and required stabilization with bovine plasma albumin."}
{"id": "PMID:212449", "title": "Conjunctivitis due to adenovirus type 19.", "content": "An outbreak of unusual conjunctivitis occurred in Seattle in the summer of 1974. We found evidence of adenovirus type 19 (Ad19) infection in 28 of 42 (67%) referred cases from whom specimens for virus isolation and/or serology were obtained. Virus was isolated from conjunctiva, throats, and/or stools, often in week 2 of illness. Ad19-related cases more frequently had severe ocular pathology, transient visual impairment, and active disease for longer than a week. Secondary illnesses were more frequent in relation to Ad19 infection (26%) than to conjunctivitis of other etiology (5%, P less than 0.05). Persons with Ad19 infection commonly experienced sore throats without coughs or fevers. No common source of infection was identified in the outbreak, and illness was unrelated to occupation, residence, or family characteristics. A 3- to 8-day incubation period was suggested by two related cases.", "contents": "Conjunctivitis due to adenovirus type 19. An outbreak of unusual conjunctivitis occurred in Seattle in the summer of 1974. We found evidence of adenovirus type 19 (Ad19) infection in 28 of 42 (67%) referred cases from whom specimens for virus isolation and/or serology were obtained. Virus was isolated from conjunctiva, throats, and/or stools, often in week 2 of illness. Ad19-related cases more frequently had severe ocular pathology, transient visual impairment, and active disease for longer than a week. Secondary illnesses were more frequent in relation to Ad19 infection (26%) than to conjunctivitis of other etiology (5%, P less than 0.05). Persons with Ad19 infection commonly experienced sore throats without coughs or fevers. No common source of infection was identified in the outbreak, and illness was unrelated to occupation, residence, or family characteristics. A 3- to 8-day incubation period was suggested by two related cases."}
{"id": "PMID:212450", "title": "Synergistic lysis of erythrocytes by Propionibacterium acnes.", "content": "Sheep and human erythrocytes, partially processed by Staphylococcus aureus or Clostridium perfringens, were susceptible to lysis in the presence of Propionibacterium acnes. P. acnes liberated a lipase that was detected on Tween 80 agar and also on phospholipase C-precipitated egg yolk agar. Such a lipase might have contributed in the process of an intensified cellular lysis. Similar reactions were attempted with Lactobacillus acidophilus, known to possess a nondiffusible lipase, and failed to produce any such reactions. The synergistic reactions, between P. acnes and C. perfringens, were compared with The classical CAMP reaction in an attempt to find a correlation with the established membrane composition of the erythrocytes involved. Synergistic reactions observed do seem to reflect the membrane composition. Such findings, besides being contributory to an understanding of the role of these organisms in the process of pathogenesis, are of importance in the elucidation of molecular organization of biomembranes. Detailed studies, involving a large number of representative anaerobic bacteria, may also help provide an avenue in anaerobic species identification.", "contents": "Synergistic lysis of erythrocytes by Propionibacterium acnes. Sheep and human erythrocytes, partially processed by Staphylococcus aureus or Clostridium perfringens, were susceptible to lysis in the presence of Propionibacterium acnes. P. acnes liberated a lipase that was detected on Tween 80 agar and also on phospholipase C-precipitated egg yolk agar. Such a lipase might have contributed in the process of an intensified cellular lysis. Similar reactions were attempted with Lactobacillus acidophilus, known to possess a nondiffusible lipase, and failed to produce any such reactions. The synergistic reactions, between P. acnes and C. perfringens, were compared with The classical CAMP reaction in an attempt to find a correlation with the established membrane composition of the erythrocytes involved. Synergistic reactions observed do seem to reflect the membrane composition. Such findings, besides being contributory to an understanding of the role of these organisms in the process of pathogenesis, are of importance in the elucidation of molecular organization of biomembranes. Detailed studies, involving a large number of representative anaerobic bacteria, may also help provide an avenue in anaerobic species identification."}
{"id": "PMID:212451", "title": "Comparison of an enzyme-linked immunosorbent assay for quantitation of rotavirus antibodies with complement fixation in an epidemiological survey.", "content": "The development of a micro-scale enzyme-linked immunosorbent assay (ELISA) with horseradish peroxidase as the marker enzyme for the detection and measurement of human rotavirus antibodies is described. A semipurified preparation of the serologically related simian agent, SA-11 virus, was used as the antigen. Test sera were reacted with antigen-sensitized wells in disposable poly-vinyl microplates. Any attached antibody was detected by the addition of peroxidase-labeled anti-species immunoglobulin (conjugate) followed by assay of the enzyme reaction with its substrate, hydrogen peroxide plus 5-aminosalicylic acid. This micro-ELISA was compared with complement fixation in a seroepidemiological study of the age prevalence of rotavirus antibody in Aboriginal and European populations living in the same outback area in Australia. The ELISA (results read with the naked eye) proved to be approximately 16 times more sensitive than complement fixation. Of Aborigines, 71% had rotavirus complement-fixing antibody, as compared to 45% of Europeans. By ELISA 100% of both populations had rotavirus antibodies. Mean antibody titers in the different age groups were higher in Aborigines than in Europeans. Antibody levels rose steeply throughout the first 20 years of life, remained high during the next 20 years, then increased again at least up to the age of 60 years. The micro-ELISA was practical, simple to perform, and more suitable than complement fixation for large seroepidemiological rotavirus studies. It also has potential for serodiagnosis of the disease, both in the laboratory and in the field.", "contents": "Comparison of an enzyme-linked immunosorbent assay for quantitation of rotavirus antibodies with complement fixation in an epidemiological survey. The development of a micro-scale enzyme-linked immunosorbent assay (ELISA) with horseradish peroxidase as the marker enzyme for the detection and measurement of human rotavirus antibodies is described. A semipurified preparation of the serologically related simian agent, SA-11 virus, was used as the antigen. Test sera were reacted with antigen-sensitized wells in disposable poly-vinyl microplates. Any attached antibody was detected by the addition of peroxidase-labeled anti-species immunoglobulin (conjugate) followed by assay of the enzyme reaction with its substrate, hydrogen peroxide plus 5-aminosalicylic acid. This micro-ELISA was compared with complement fixation in a seroepidemiological study of the age prevalence of rotavirus antibody in Aboriginal and European populations living in the same outback area in Australia. The ELISA (results read with the naked eye) proved to be approximately 16 times more sensitive than complement fixation. Of Aborigines, 71% had rotavirus complement-fixing antibody, as compared to 45% of Europeans. By ELISA 100% of both populations had rotavirus antibodies. Mean antibody titers in the different age groups were higher in Aborigines than in Europeans. Antibody levels rose steeply throughout the first 20 years of life, remained high during the next 20 years, then increased again at least up to the age of 60 years. The micro-ELISA was practical, simple to perform, and more suitable than complement fixation for large seroepidemiological rotavirus studies. It also has potential for serodiagnosis of the disease, both in the laboratory and in the field."}
{"id": "PMID:212452", "title": "Solid-phase enzyme-linked immunosorbent assay for detection of hepatitis A virus.", "content": "An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of hepatitis A virus in human fecal specimens. Investigations with 88 fecal specimens from 77 patients with suspected viral hepatitis and 8 of their household contacts showed that ELISA was as specific and sensitive as radioimmunoassay and almost as sensitive as immune electron microscopy. The ELISA is quick and simple to perform, does not require sophisticated technical equipment, and can be read with the naked eye, making it suitable for field work and rapid diagnosis.", "contents": "Solid-phase enzyme-linked immunosorbent assay for detection of hepatitis A virus. An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of hepatitis A virus in human fecal specimens. Investigations with 88 fecal specimens from 77 patients with suspected viral hepatitis and 8 of their household contacts showed that ELISA was as specific and sensitive as radioimmunoassay and almost as sensitive as immune electron microscopy. The ELISA is quick and simple to perform, does not require sophisticated technical equipment, and can be read with the naked eye, making it suitable for field work and rapid diagnosis."}
{"id": "PMID:212453", "title": "Measurement of rotavirus antibody by an enzyme-linked immunosorbent assay blocking assay.", "content": "A new method for the measurement of rotavirus antibody is described, utilizing the system of enzyme-linked immunosorbent assay (ELISA). In this method, serum is incubated with a fixed amount of rotavirus antigen, and the amount of antibody is determined by measuring the amount of unneutralized antigen. Such an assay system proved to be as efficient as the other available rotaviral antibody systems. The ELISA blocking assay also has the advantages of not requiring purified or gnotobiotic antigen and of being able to measure rotaviral antibody in all animal species.", "contents": "Measurement of rotavirus antibody by an enzyme-linked immunosorbent assay blocking assay. A new method for the measurement of rotavirus antibody is described, utilizing the system of enzyme-linked immunosorbent assay (ELISA). In this method, serum is incubated with a fixed amount of rotavirus antigen, and the amount of antibody is determined by measuring the amount of unneutralized antigen. Such an assay system proved to be as efficient as the other available rotaviral antibody systems. The ELISA blocking assay also has the advantages of not requiring purified or gnotobiotic antigen and of being able to measure rotaviral antibody in all animal species."}
{"id": "PMID:212454", "title": "Neutralization of human serum lysozyme by sodium polyanethol sulfonate but not by sodium amylosulfate.", "content": "Sodium polyanethol sulfonate (SPS) at 500 microgram/ml, but not sodium amylosulfate (SAS) at 500 microgram/ml, precipitated egg white lysozyme (1 mg and 50 microgram of lysozyme per ml) as determined with the assay strain Micrococcus lysodeikticus ATCC 4698. Fresh and heat-inactivated (56 degrees C, 30 min) human serum (80%, vol/vol) killed M. lysodeikticus (10(4) bacteria per ml at zero time) within 1 to 2 h after exposure. Addition of 250 to 500 microgram of SPS per ml to fresh human serum protected M. lysodeikticus for 22 h as effectively as absorption of either fresh or heat-inactivated human serum with bentonite (10 mg/ml of serum, 10 min, 37 degrees C); the latter procedure is known to remove serum lysozyme. In contrast, SAS at 250 and 500 microgram/ml of serum retarded killing of the assay bacteria for periods of 4 h; after overnight (22 h) incubation, however, the number of M. lysodeikticus survivors had decreased significantly. The finding that SPS, but not SAS, at 250 to 500 microgram/ml effectively neutralized serum lysozyme-mediated killing of a lysozyme-sensitive assay strain may be of relevance with respect to laboratory processing of human blood culture specimens.", "contents": "Neutralization of human serum lysozyme by sodium polyanethol sulfonate but not by sodium amylosulfate. Sodium polyanethol sulfonate (SPS) at 500 microgram/ml, but not sodium amylosulfate (SAS) at 500 microgram/ml, precipitated egg white lysozyme (1 mg and 50 microgram of lysozyme per ml) as determined with the assay strain Micrococcus lysodeikticus ATCC 4698. Fresh and heat-inactivated (56 degrees C, 30 min) human serum (80%, vol/vol) killed M. lysodeikticus (10(4) bacteria per ml at zero time) within 1 to 2 h after exposure. Addition of 250 to 500 microgram of SPS per ml to fresh human serum protected M. lysodeikticus for 22 h as effectively as absorption of either fresh or heat-inactivated human serum with bentonite (10 mg/ml of serum, 10 min, 37 degrees C); the latter procedure is known to remove serum lysozyme. In contrast, SAS at 250 and 500 microgram/ml of serum retarded killing of the assay bacteria for periods of 4 h; after overnight (22 h) incubation, however, the number of M. lysodeikticus survivors had decreased significantly. The finding that SPS, but not SAS, at 250 to 500 microgram/ml effectively neutralized serum lysozyme-mediated killing of a lysozyme-sensitive assay strain may be of relevance with respect to laboratory processing of human blood culture specimens."}
{"id": "PMID:212456", "title": "GABA-ergic pathways in the goldfish retina.", "content": "A high-affinity uptake mechanism for [3H]-gamma-aminobutyric acid (GABA) has been localized to type H1 cone horizontal cells and type Ab pyriform amacrine cells in the retina of the goldfish by light and electron microscopy autoradiography. By stimulating isolated retinas with colored lights during incubation we have been able to use [3H]-GABA uptake as a probe of light-evoked changes in membrane potential. All colors of lights increase and darkness decreases [3H]-GABA uptake by H1 cone horizontal cells. Our model of voltage dependence of GABA uptake predicts that all colors of light should hyperpolarize H1 cone horizontal cells and other investigators have shown by intracellular recording and dye-marking that type H1 cone horizontal cells hyperpolarize to all wavelengths of light. We have also obtained evidence that dark-induced depolarization of cone horizontal cells leads to release of GABA. Type Ab pyriform amacrine cells show maximal [3H]-GABA uptake in darkness and when exposed to green or blue lights, but red lights dramatically suppress uptake. We predict these neurons to be red-depolarizing, and recent intracellular recordings and dye-marking by Famiglietti et al. ('77) support our conclusions. Synaptic relations of apparently GABA-ergic neurons were investigated in the electron microscope. We propose type H1 cone horizontal cells to be both pre- and post-synaptic to red-sensitive cones and type Ab pyriform amacrine cells to be both pre- and post-synaptic to red-sensitive center-depolarizing bipolar cells.", "contents": "GABA-ergic pathways in the goldfish retina. A high-affinity uptake mechanism for [3H]-gamma-aminobutyric acid (GABA) has been localized to type H1 cone horizontal cells and type Ab pyriform amacrine cells in the retina of the goldfish by light and electron microscopy autoradiography. By stimulating isolated retinas with colored lights during incubation we have been able to use [3H]-GABA uptake as a probe of light-evoked changes in membrane potential. All colors of lights increase and darkness decreases [3H]-GABA uptake by H1 cone horizontal cells. Our model of voltage dependence of GABA uptake predicts that all colors of light should hyperpolarize H1 cone horizontal cells and other investigators have shown by intracellular recording and dye-marking that type H1 cone horizontal cells hyperpolarize to all wavelengths of light. We have also obtained evidence that dark-induced depolarization of cone horizontal cells leads to release of GABA. Type Ab pyriform amacrine cells show maximal [3H]-GABA uptake in darkness and when exposed to green or blue lights, but red lights dramatically suppress uptake. We predict these neurons to be red-depolarizing, and recent intracellular recordings and dye-marking by Famiglietti et al. ('77) support our conclusions. Synaptic relations of apparently GABA-ergic neurons were investigated in the electron microscope. We propose type H1 cone horizontal cells to be both pre- and post-synaptic to red-sensitive cones and type Ab pyriform amacrine cells to be both pre- and post-synaptic to red-sensitive center-depolarizing bipolar cells."}
{"id": "PMID:212461", "title": "Electron microscopy of neoplasms of pancreatic islet cells.", "content": "Neoplasms of pancreatic islet cells that produce widely divergent clinical syndromes cannot be distinguished from one another by conventional microscopy. Differentiation among these tumors by electron microscopy is possible in some cases only. Coordinated clinical evaluation, histochemical and ultrastructural studies, and assay of serum and neoplastic tissue for various polypeptide hormones afford the best characterization of these neoplasms.", "contents": "Electron microscopy of neoplasms of pancreatic islet cells. Neoplasms of pancreatic islet cells that produce widely divergent clinical syndromes cannot be distinguished from one another by conventional microscopy. Differentiation among these tumors by electron microscopy is possible in some cases only. Coordinated clinical evaluation, histochemical and ultrastructural studies, and assay of serum and neoplastic tissue for various polypeptide hormones afford the best characterization of these neoplasms."}
{"id": "PMID:212462", "title": "Ulcers associated with the swollen leg.", "content": "A number of disparate conditions may produce ulcers in swollen legs. The most frequent causative condition is venous stasis; other causal disorders are lymphatic obstruction, mixed vascular anomalies, benign and malignant neoplasms and a number of miscellaneous conditions. Careful attention to cutaneous signs of these conditions may be helpful in arriving at an accurate diagnosis and appropriate therapy.", "contents": "Ulcers associated with the swollen leg. A number of disparate conditions may produce ulcers in swollen legs. The most frequent causative condition is venous stasis; other causal disorders are lymphatic obstruction, mixed vascular anomalies, benign and malignant neoplasms and a number of miscellaneous conditions. Careful attention to cutaneous signs of these conditions may be helpful in arriving at an accurate diagnosis and appropriate therapy."}
{"id": "PMID:212459", "title": "Phospholipids of a bone matrix calcification nucleator.", "content": "Phospholipids of a bone matrix calcification nucleator are identified as mono and diphosphoinositides and phosphatidyl serine. The nucleator, a protein-phospholipid complex, was dissociated by acidified-solvent porous-glass column chromatography. Analysis was by gas-liquid chromatography.", "contents": "Phospholipids of a bone matrix calcification nucleator. Phospholipids of a bone matrix calcification nucleator are identified as mono and diphosphoinositides and phosphatidyl serine. The nucleator, a protein-phospholipid complex, was dissociated by acidified-solvent porous-glass column chromatography. Analysis was by gas-liquid chromatography."}
{"id": "PMID:212463", "title": "Significance of high-density lipoprotein cholesterol.", "content": "The central importance of elevated blood cholesterol levels in the process of atherosclerotic heart disease (ASHD) is firmly established. Cholesterol is transported in the blood in conjunction with protein as a lipoprotein complex. The low-density lipoproteins (LDL) carry the bulk of the blood cholesterol. The high-density lipoproteins (HDL) occur in much smaller amounts. Recently it has been demonstrated that not only is the cholesterol carried in the HDL fraction not harmful, but appears to be protective against the development of ASHD. Data from Framingham and elsewhere seem consistent with this observation. The HDS apparently represent the fraction concerned with the efflux of cholesterol from the tissues, so that higher levels may represent a heightened cholesterol-riddance mechanism. Thus far, two circumstances seem to be associated with elevated levels of HDL--physical exercise and ethanol ingestion. The importance of these observations in the clinical management of the patient at risk is discussed.", "contents": "Significance of high-density lipoprotein cholesterol. The central importance of elevated blood cholesterol levels in the process of atherosclerotic heart disease (ASHD) is firmly established. Cholesterol is transported in the blood in conjunction with protein as a lipoprotein complex. The low-density lipoproteins (LDL) carry the bulk of the blood cholesterol. The high-density lipoproteins (HDL) occur in much smaller amounts. Recently it has been demonstrated that not only is the cholesterol carried in the HDL fraction not harmful, but appears to be protective against the development of ASHD. Data from Framingham and elsewhere seem consistent with this observation. The HDS apparently represent the fraction concerned with the efflux of cholesterol from the tissues, so that higher levels may represent a heightened cholesterol-riddance mechanism. Thus far, two circumstances seem to be associated with elevated levels of HDL--physical exercise and ethanol ingestion. The importance of these observations in the clinical management of the patient at risk is discussed."}
{"id": "PMID:212474", "title": "Differential inhibitory effects of 5-bromodeoxyuridine on vaccinia and monkeypox viruses.", "content": "Replication of vaccinia and monkeypox viruses was impeded in the presence of 5-bromodeoxyuridine (BUdR) in RL-33 cells derived from rabbit lung tissue. The different degree of inhibition was found among strains of those viruses, in which it was evident that five strains (CV-1, Lister, IHD, Dairen-I and Ikeda) of vaccinia viruses resulted in more reduced yields of infectious virus than four strains (Sen-19, Orang Utan, Copenhagen and Sierra Leone) of monkeypox viruses. There was also strain variation in BUdR sensitivity within vaccinia viruses but not in the case of monkeypox viruses.", "contents": "Differential inhibitory effects of 5-bromodeoxyuridine on vaccinia and monkeypox viruses. Replication of vaccinia and monkeypox viruses was impeded in the presence of 5-bromodeoxyuridine (BUdR) in RL-33 cells derived from rabbit lung tissue. The different degree of inhibition was found among strains of those viruses, in which it was evident that five strains (CV-1, Lister, IHD, Dairen-I and Ikeda) of vaccinia viruses resulted in more reduced yields of infectious virus than four strains (Sen-19, Orang Utan, Copenhagen and Sierra Leone) of monkeypox viruses. There was also strain variation in BUdR sensitivity within vaccinia viruses but not in the case of monkeypox viruses."}
{"id": "PMID:212475", "title": "Possible windborne spread of bluetongue to Portugal, June-July 1956.", "content": "The possible sources for the epidemic of bluetongue in Portugal at the beginning of July 1956 were examined. Introduction through authorized importation of domestic or wild ruminants was not feasible, since no cattle, sheep or goats were imported and the wild ruminants were confined to Lisbon Zoo, which was too far from the initial outbreaks. Weather maps were examined to see if the wind could have carried infected Culicoides midges from North Africa. On 21 June 1956 infected midges in Morocco could have been taken offshore by southeast winds and then carried by south winds unusual at that time of year to the south coast of Portugal. The 200-300 km sea crossing would have taken some 10 h and been by day when air temperatures near the sea surface were about 18-20 C. Bluetongue had not been reported at that time in Moroccco, and the possibility of the presence of the virus in moroccan animals without clinical signs is discussed.", "contents": "Possible windborne spread of bluetongue to Portugal, June-July 1956. The possible sources for the epidemic of bluetongue in Portugal at the beginning of July 1956 were examined. Introduction through authorized importation of domestic or wild ruminants was not feasible, since no cattle, sheep or goats were imported and the wild ruminants were confined to Lisbon Zoo, which was too far from the initial outbreaks. Weather maps were examined to see if the wind could have carried infected Culicoides midges from North Africa. On 21 June 1956 infected midges in Morocco could have been taken offshore by southeast winds and then carried by south winds unusual at that time of year to the south coast of Portugal. The 200-300 km sea crossing would have taken some 10 h and been by day when air temperatures near the sea surface were about 18-20 C. Bluetongue had not been reported at that time in Moroccco, and the possibility of the presence of the virus in moroccan animals without clinical signs is discussed."}
{"id": "PMID:212476", "title": "The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice.", "content": "The pathogenicity for mice of two mutants of herpes simplex virus (type 1 and type 2), which fail to induce thymidine kinase, were compared with their respective parent strains. The mutants were much less virulent than the parents following either intracerebral or peripheral inoculation. The replication of the virus at the site of inoculation and its progression into the nervous system were studied. Following a very large inoculum in the ear, the type 1 mutant was found to establish a latent infection in the cervical dorsal root ganglia. Mice inoculated intracerebrally with small doses of the mutant viruses were solidly immune to challenge with lethal doses of the parent strain.", "contents": "The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. The pathogenicity for mice of two mutants of herpes simplex virus (type 1 and type 2), which fail to induce thymidine kinase, were compared with their respective parent strains. The mutants were much less virulent than the parents following either intracerebral or peripheral inoculation. The replication of the virus at the site of inoculation and its progression into the nervous system were studied. Following a very large inoculum in the ear, the type 1 mutant was found to establish a latent infection in the cervical dorsal root ganglia. Mice inoculated intracerebrally with small doses of the mutant viruses were solidly immune to challenge with lethal doses of the parent strain."}
{"id": "PMID:212477", "title": "A search for faecal viruses in new-born and other infants.", "content": "Faecal specimens were collected at weekly intervals over the winter months from 141 new-born infants without diarrhoea. Contrary to the findings in other studies, no viruses were detected by electron micriscopy or culture in any of these specimens. Over the same period faecal specimens were collected from 84 infants up to four years of age admitted to hospital. Rotaviruses or adenoviruses were found in 48% of infants with gastroenteritis. Enteroviruses and other small round virus-like particles were found in infants both with and without gastroenteritis. No viruses or pathogenic bacteria could be found in 34% of specimens from infants with gastroenteritis.", "contents": "A search for faecal viruses in new-born and other infants. Faecal specimens were collected at weekly intervals over the winter months from 141 new-born infants without diarrhoea. Contrary to the findings in other studies, no viruses were detected by electron micriscopy or culture in any of these specimens. Over the same period faecal specimens were collected from 84 infants up to four years of age admitted to hospital. Rotaviruses or adenoviruses were found in 48% of infants with gastroenteritis. Enteroviruses and other small round virus-like particles were found in infants both with and without gastroenteritis. No viruses or pathogenic bacteria could be found in 34% of specimens from infants with gastroenteritis."}
{"id": "PMID:212478", "title": "Stool viruses in babies in Glasgow 2. Investigation of normal newborns in hospital.", "content": "The stools of 37 newborn babies born in hospital were examined for the presence of virus. An extract of every stool passed by each baby was examined in the electron microscopy and inoculated into cell cultures. The babies were delivered in four separate maternity units (A-D). All the babies from unit A and C(9 babies) were found to be excreting rotavirus though none showed any evidence of diarrhoea. Two of the babies also excreted astrovirus. Subsequently unit A was closed for cleaning and, on reopening with more restrictions on visitors, a further 19 babies were examined. No virus was found in any of their stools, nor was virus observed in the stools of babies from units B and D, where visiting was also more restricted. Visiting restrictions in these units excluded older siblings of the babies. No virus was cultured from any stools in this study.", "contents": "Stool viruses in babies in Glasgow 2. Investigation of normal newborns in hospital. The stools of 37 newborn babies born in hospital were examined for the presence of virus. An extract of every stool passed by each baby was examined in the electron microscopy and inoculated into cell cultures. The babies were delivered in four separate maternity units (A-D). All the babies from unit A and C(9 babies) were found to be excreting rotavirus though none showed any evidence of diarrhoea. Two of the babies also excreted astrovirus. Subsequently unit A was closed for cleaning and, on reopening with more restrictions on visitors, a further 19 babies were examined. No virus was found in any of their stools, nor was virus observed in the stools of babies from units B and D, where visiting was also more restricted. Visiting restrictions in these units excluded older siblings of the babies. No virus was cultured from any stools in this study."}
{"id": "PMID:212479", "title": "Studies of louping-ill virus (Flavivirus group) in wild red grouse (Lagopus lagopus scoticus).", "content": "Studies were made to find evidence of louping-ill virus infection in free-living red grouse and relate this to their breeding success. In areas where ticks were abundant 61 (84%) adult grouse had antibody to the virus compared with 1 (10%) in areas where ticks were relatively scarce. Of 162 chicks tested 25 were shown to be viraemic. Infected chicks were of significantly less weight than comparably aged uninfected birds and the probability that they died was much greater than that of uninfected birds. It is concluded that the relatively poor breeding success in areas of high tick numbers was principally due to infection with louping-ill virus. The susceptibility of the red grouse to infection is discussed.", "contents": "Studies of louping-ill virus (Flavivirus group) in wild red grouse (Lagopus lagopus scoticus). Studies were made to find evidence of louping-ill virus infection in free-living red grouse and relate this to their breeding success. In areas where ticks were abundant 61 (84%) adult grouse had antibody to the virus compared with 1 (10%) in areas where ticks were relatively scarce. Of 162 chicks tested 25 were shown to be viraemic. Infected chicks were of significantly less weight than comparably aged uninfected birds and the probability that they died was much greater than that of uninfected birds. It is concluded that the relatively poor breeding success in areas of high tick numbers was principally due to infection with louping-ill virus. The susceptibility of the red grouse to infection is discussed."}
{"id": "PMID:212483", "title": "Immunofluorescent analysis of murine leukemia virus-infected cells by flow microfluorometry.", "content": "Flow microfluorometric assay with a Cytofluorograf model 4801 in combination with immunofluorescence was applied to the quantitative assay of cells exogenously infected with mouse leukemia viruses and to the chemical induction of virus in AKR cells. The Cytofluorograf provides sensitivity equal to the visual method and is capable of assaying up to 5000 cells/sec with specificity equivalent to that of the direct visual immunofluorescence assay, thereby providing a large, statistically valid sampling in a fraction of the time required by visual counting. Flow microfluorometry also provides a method of quantitatively resolving fluorescent cell populations on the basis of relative size and degree of fluorescence.", "contents": "Immunofluorescent analysis of murine leukemia virus-infected cells by flow microfluorometry. Flow microfluorometric assay with a Cytofluorograf model 4801 in combination with immunofluorescence was applied to the quantitative assay of cells exogenously infected with mouse leukemia viruses and to the chemical induction of virus in AKR cells. The Cytofluorograf provides sensitivity equal to the visual method and is capable of assaying up to 5000 cells/sec with specificity equivalent to that of the direct visual immunofluorescence assay, thereby providing a large, statistically valid sampling in a fraction of the time required by visual counting. Flow microfluorometry also provides a method of quantitatively resolving fluorescent cell populations on the basis of relative size and degree of fluorescence."}
{"id": "PMID:212484", "title": "Sensitive new in vitro bioassay for melanocyte-stimulating activity using the skin of Anolis carolinensis.", "content": "An accurate, highly reproducible and sensitive bioassay for melanocyte-stimulating hormone (MSH) using the skin of Anolis carolinensis in vitro is described. The time taken for green Anolis skin fragments to change to a specific, visually assessed, green-brown color is dose-related, and this forms the basis of the new assay. The method is simple to perform, and 1 person may assay 20 samples in a day using the dorsal skin from a single adult lizard. The mean dose-response ranges between 48 X 10(-12) and 375 X 12(-12) M (38 to 625 pg/ml). Using the assay, alpha-MSH, beta-MSH, ACTH (4-10), and ACTH (1-10) were equipotent on a molar basis. For repeated bioassay of rat pituitary extracts, the dose-response curves were highly significant, and only 1 of the 9 pituitary dose-response curves deviated significantly from the slope of the standard alpha-MSH curve. The index of precision, lambda, for the 9 pituitary bioassays ranged between 0.037 and 0.081, while the mean 95% fiducial limits were -6.6 and 7.1% on either side of the estimated potency. The new rate method is compared with an earlier quantal method which also uses the isolated skin of Anolis carolinensis. The quantal method does not have dose-response characteristics and is therefore less accurate and reproducible than the new method; the coefficient of variation for repeated bioassay of the same pituitary extracts ranged from between 12 to 20% for the quantal method and between 2.9 to 5.7% for the new rate method.", "contents": "Sensitive new in vitro bioassay for melanocyte-stimulating activity using the skin of Anolis carolinensis. An accurate, highly reproducible and sensitive bioassay for melanocyte-stimulating hormone (MSH) using the skin of Anolis carolinensis in vitro is described. The time taken for green Anolis skin fragments to change to a specific, visually assessed, green-brown color is dose-related, and this forms the basis of the new assay. The method is simple to perform, and 1 person may assay 20 samples in a day using the dorsal skin from a single adult lizard. The mean dose-response ranges between 48 X 10(-12) and 375 X 12(-12) M (38 to 625 pg/ml). Using the assay, alpha-MSH, beta-MSH, ACTH (4-10), and ACTH (1-10) were equipotent on a molar basis. For repeated bioassay of rat pituitary extracts, the dose-response curves were highly significant, and only 1 of the 9 pituitary dose-response curves deviated significantly from the slope of the standard alpha-MSH curve. The index of precision, lambda, for the 9 pituitary bioassays ranged between 0.037 and 0.081, while the mean 95% fiducial limits were -6.6 and 7.1% on either side of the estimated potency. The new rate method is compared with an earlier quantal method which also uses the isolated skin of Anolis carolinensis. The quantal method does not have dose-response characteristics and is therefore less accurate and reproducible than the new method; the coefficient of variation for repeated bioassay of the same pituitary extracts ranged from between 12 to 20% for the quantal method and between 2.9 to 5.7% for the new rate method."}
{"id": "PMID:212485", "title": "Theophylline incorporation into the nucleic acids of theophylline-stimulated melanoma cells.", "content": "Theophyllin, an inhibitor of cAMP-degrading phosphodiesterase, stimulates melanin biosynthesis in cultures of RPMI 3460 hamster melanoma cells. Although theophylline does produce an initial transient elevation of intracellular cAMP levels, long-term treatment with theophylline produces a significant decrease in cAMP content. There is an inhibition of the theophylline stimulation by dibutyryl-cAMP; this is apparently caused by interference of dibutyryl-cAMP with the uptake and incorporation of theophylline, as shown by experiments with 3H-theophylline. An alternative theory is that theophylline, being a methylxanthine compound, is metabolized by the cell and possibly causes melanotic stimulation by becoming incorporated into cellular nucleic acids or by altering the normal nucleic acid metabolism. The following observations are consistent with this theory: (u) 3H-theophylline was incorporated into both trichloroacetic acid (TCA)-soluble and TCA-insoluble cell fractions; most of the insoluble label became soluble after digestion with ribonuclease and deoxyribonuclease. (2) These nuclease digests of the 3H-theophylline-labeled TCA-insoluble cell fractions contained 3H-labeled material that chromatographed differently from normal nucleotides on ion exchange thin layer sheets. (3) The acid-soluble pool of 3H label disappeared rapidly while both the insoluble label and the induction of melanogenesis remained stable for 50 hr after the removal of exogenous 3H-theophylline.", "contents": "Theophylline incorporation into the nucleic acids of theophylline-stimulated melanoma cells. Theophyllin, an inhibitor of cAMP-degrading phosphodiesterase, stimulates melanin biosynthesis in cultures of RPMI 3460 hamster melanoma cells. Although theophylline does produce an initial transient elevation of intracellular cAMP levels, long-term treatment with theophylline produces a significant decrease in cAMP content. There is an inhibition of the theophylline stimulation by dibutyryl-cAMP; this is apparently caused by interference of dibutyryl-cAMP with the uptake and incorporation of theophylline, as shown by experiments with 3H-theophylline. An alternative theory is that theophylline, being a methylxanthine compound, is metabolized by the cell and possibly causes melanotic stimulation by becoming incorporated into cellular nucleic acids or by altering the normal nucleic acid metabolism. The following observations are consistent with this theory: (u) 3H-theophylline was incorporated into both trichloroacetic acid (TCA)-soluble and TCA-insoluble cell fractions; most of the insoluble label became soluble after digestion with ribonuclease and deoxyribonuclease. (2) These nuclease digests of the 3H-theophylline-labeled TCA-insoluble cell fractions contained 3H-labeled material that chromatographed differently from normal nucleotides on ion exchange thin layer sheets. (3) The acid-soluble pool of 3H label disappeared rapidly while both the insoluble label and the induction of melanogenesis remained stable for 50 hr after the removal of exogenous 3H-theophylline."}
{"id": "PMID:212486", "title": "Viral immune complexes in systemic lupus erythematosus: C-type viral complex deposition in skin.", "content": "Punch biopsies were examined by indirect immunofluorescence for immune complex deposits containing C-type viral antigen. Antisera specific for immunoglobulins and HEL-12 virus mediated fluorescence at the dermal-epidermal junction and in vessel walls of 16 of 16 biopsies involved skin from patients with systemic lupus erythematosus (SLE). Preimmune sera did not mediate fluorescence and gradient purified HEL-12 virus, simian sarcoma virus and baboon endogenous virus but not Rous sarcoma virus blocked the reaction of anti-HEL-12 virus serum with SLE tissue. Ten biopsies from uninvolved skin of the patients with SLE did not react with the antiviral serum, nor did tissue from 9 patients with discoid lupus erythematosus, psoriasis, bullous pemphigoid or normal skin. These data support the hypothesis that C-type viral immune complexes participate in the pathogenesis of SLE.", "contents": "Viral immune complexes in systemic lupus erythematosus: C-type viral complex deposition in skin. Punch biopsies were examined by indirect immunofluorescence for immune complex deposits containing C-type viral antigen. Antisera specific for immunoglobulins and HEL-12 virus mediated fluorescence at the dermal-epidermal junction and in vessel walls of 16 of 16 biopsies involved skin from patients with systemic lupus erythematosus (SLE). Preimmune sera did not mediate fluorescence and gradient purified HEL-12 virus, simian sarcoma virus and baboon endogenous virus but not Rous sarcoma virus blocked the reaction of anti-HEL-12 virus serum with SLE tissue. Ten biopsies from uninvolved skin of the patients with SLE did not react with the antiviral serum, nor did tissue from 9 patients with discoid lupus erythematosus, psoriasis, bullous pemphigoid or normal skin. These data support the hypothesis that C-type viral immune complexes participate in the pathogenesis of SLE."}
{"id": "PMID:212488", "title": "Localization of hepatitis A antigen in marmoset organs during acute infection with hepatitis A virus.", "content": "Twelve marmosets (Saguinus mystax) were inoculated intravenously (iv) with hepatitis A virus (HAV). One died early (day 12); seven were sacrificed at the time of elevation in level of alanine aminotransferase (serum glutamic-pyruvic transaminase), and four without elevation were not sacrificed but seroconverted. In the seven marmosets sacrificed during the acute stage of illness, hepatitis A antigen (HA Ag) was detected in the liver by immunofluorescence in all cases, by immune electron microscopy in four, and by enzyme-linked immunosorbent assay (ELISA) in three. The HA Ag appeared by immunofluorescence as very fine granules in the cytoplasm of hepatocytes and Kupffer cells. The HA Ag could not be detected by immunofluorescence in biopsy specimens taken from the duodenum, jejunum, ileum, or transverse colon in any of eight marmosets in which necropsy was performed during the acute or preacute stage of illness. These findings suggest that the gut is not involved during the acute phase of HAV infection following iv inoculation into marmosets. The ELISA results showed that only three of 12 marmoset livers obtained during the acute phase of HAV infection could be used as an antigen source in serologic testing for antibody to HA Ag. Thus, marmoset livers were no better as a source of HA Ag than acute-phase stools from patients with type A hepatitis.", "contents": "Localization of hepatitis A antigen in marmoset organs during acute infection with hepatitis A virus. Twelve marmosets (Saguinus mystax) were inoculated intravenously (iv) with hepatitis A virus (HAV). One died early (day 12); seven were sacrificed at the time of elevation in level of alanine aminotransferase (serum glutamic-pyruvic transaminase), and four without elevation were not sacrificed but seroconverted. In the seven marmosets sacrificed during the acute stage of illness, hepatitis A antigen (HA Ag) was detected in the liver by immunofluorescence in all cases, by immune electron microscopy in four, and by enzyme-linked immunosorbent assay (ELISA) in three. The HA Ag appeared by immunofluorescence as very fine granules in the cytoplasm of hepatocytes and Kupffer cells. The HA Ag could not be detected by immunofluorescence in biopsy specimens taken from the duodenum, jejunum, ileum, or transverse colon in any of eight marmosets in which necropsy was performed during the acute or preacute stage of illness. These findings suggest that the gut is not involved during the acute phase of HAV infection following iv inoculation into marmosets. The ELISA results showed that only three of 12 marmoset livers obtained during the acute phase of HAV infection could be used as an antigen source in serologic testing for antibody to HA Ag. Thus, marmoset livers were no better as a source of HA Ag than acute-phase stools from patients with type A hepatitis."}
{"id": "PMID:212489", "title": "The adrenal response to exogenous adrenocorticotrophin in patients with infections due to Neisseria meningitidis.", "content": "The adrenal response to a soluble form of beta1-24-corticotropin (tetracosactrin [ACTH]: 250 microgram administered intramuscularly) was studied in 28 patients with meningitis due to Neisseria meningitidis (21 with petechiae and seven without) and in six patients with Salmonella typhi bacteremia. Six normal subjects also were tested for adrenal responsiveness at four different times of the day (8 A.M., 12 noon, 4 P.M., and 10 P.M.) and served as controls. The results showed that, whatever the time of testing, patients with meningococcal infections and typhoid fever had unstimulated (basal) levels of plasma cortisol above the 99% confidence limits for the mean unstimulated cortisol levels for the normal subjects. Furthermore, although patients with meningitis without petechiae and subjects with S. typhi bacteremia responded to ACTH stimulation in a manner similar to that of the normal subjects, most subjects with meningitis with petechiae did not have increased levels of plasma cortisol after treatment with ACTH. This lack of response could not be ascribed entirely to the higher basal levels of plasma cortisol in these patients. Patients with meningitis associated with petechiae may have a relatively decreased adrenal response to stimulation with exogenous ACTH.", "contents": "The adrenal response to exogenous adrenocorticotrophin in patients with infections due to Neisseria meningitidis. The adrenal response to a soluble form of beta1-24-corticotropin (tetracosactrin [ACTH]: 250 microgram administered intramuscularly) was studied in 28 patients with meningitis due to Neisseria meningitidis (21 with petechiae and seven without) and in six patients with Salmonella typhi bacteremia. Six normal subjects also were tested for adrenal responsiveness at four different times of the day (8 A.M., 12 noon, 4 P.M., and 10 P.M.) and served as controls. The results showed that, whatever the time of testing, patients with meningococcal infections and typhoid fever had unstimulated (basal) levels of plasma cortisol above the 99% confidence limits for the mean unstimulated cortisol levels for the normal subjects. Furthermore, although patients with meningitis without petechiae and subjects with S. typhi bacteremia responded to ACTH stimulation in a manner similar to that of the normal subjects, most subjects with meningitis with petechiae did not have increased levels of plasma cortisol after treatment with ACTH. This lack of response could not be ascribed entirely to the higher basal levels of plasma cortisol in these patients. Patients with meningitis associated with petechiae may have a relatively decreased adrenal response to stimulation with exogenous ACTH."}
{"id": "PMID:212490", "title": "Peroxidase-labeled antibody technique for rapid detection of mouse hepatitis virus in cases of natural outbreaks.", "content": "A recent outbreak of hepatitis in mice at the Laboratory Animals Centre (Surrey, England) is described. The only strains of mice that showed clinical symptoms and typical liver lesions were the nude (nu/nu) and obese mice. Although other inbred strains showed no clinical symptoms, all strains seroconverted. Neutralization typing of the mouse hepatitis virus showed it to be type 1, a hepatotropic strain of low virulence, a finding that was consistent with the pathology of the disease. Because of recurring outbreaks of disease caused by this strain and other strains of MHV in the United Kingdom, a rapid method for diagnosis in tissue culture was devised, employing the peroxidase enzyme-labeled antibody technique for detection of mouse hepatitis virus in L-929 cells.", "contents": "Peroxidase-labeled antibody technique for rapid detection of mouse hepatitis virus in cases of natural outbreaks. A recent outbreak of hepatitis in mice at the Laboratory Animals Centre (Surrey, England) is described. The only strains of mice that showed clinical symptoms and typical liver lesions were the nude (nu/nu) and obese mice. Although other inbred strains showed no clinical symptoms, all strains seroconverted. Neutralization typing of the mouse hepatitis virus showed it to be type 1, a hepatotropic strain of low virulence, a finding that was consistent with the pathology of the disease. Because of recurring outbreaks of disease caused by this strain and other strains of MHV in the United Kingdom, a rapid method for diagnosis in tissue culture was devised, employing the peroxidase enzyme-labeled antibody technique for detection of mouse hepatitis virus in L-929 cells."}
{"id": "PMID:212500", "title": "Depressant action of lithium at the crayfish neuromuscular junction: pre- and postsynaptic effects.", "content": "1. The effects of replacement of external sodium ions with lithium have been studied at the excitatory neuromuscular junction of the crayfish. 2. Intracellularly recorded excitatory junctional potentials fall 45% in amplitude in the first 10 min after lithium substitution, and fail irreversibly in 48--120 min. 3. The quantal content of extracellularly recorded excitatory junctional potentials declines 25--70% within the first 10 min of Li+ exposure. During the next 40--120 min the nerve terminal potentials and quantal release at individual synapses fail simultaneously and irreversibly. 4. The mean amplitude of the spontaneous miniature excitatory junctional potentials (m.e.j.p.s) is reduced 13% by Li+ substitution, but recovers upon restoration of sodium. The mean frequency of m.e.j.p.s rises steadily during Li+ exposure, and continues to increase after reintroduction of Na+. 5. The postsynaptic response to iontophoretically applied L-glutamate falls 35--40% in 10 min, but never falls below 45% of the control level. The effect on the glutamate response is completely reversible with sodium restoration. 6. The effective resistance of the postsynpatic cells is unaffected or only increased slightly by lithium substitution. 7. Thus, the primary mechanism of transmission block by lithium appears to be decreased transmitter release and inexcitability of presynaptic terminals, probably as a result of intracellular accumulation of lithium.", "contents": "Depressant action of lithium at the crayfish neuromuscular junction: pre- and postsynaptic effects. 1. The effects of replacement of external sodium ions with lithium have been studied at the excitatory neuromuscular junction of the crayfish. 2. Intracellularly recorded excitatory junctional potentials fall 45% in amplitude in the first 10 min after lithium substitution, and fail irreversibly in 48--120 min. 3. The quantal content of extracellularly recorded excitatory junctional potentials declines 25--70% within the first 10 min of Li+ exposure. During the next 40--120 min the nerve terminal potentials and quantal release at individual synapses fail simultaneously and irreversibly. 4. The mean amplitude of the spontaneous miniature excitatory junctional potentials (m.e.j.p.s) is reduced 13% by Li+ substitution, but recovers upon restoration of sodium. The mean frequency of m.e.j.p.s rises steadily during Li+ exposure, and continues to increase after reintroduction of Na+. 5. The postsynaptic response to iontophoretically applied L-glutamate falls 35--40% in 10 min, but never falls below 45% of the control level. The effect on the glutamate response is completely reversible with sodium restoration. 6. The effective resistance of the postsynpatic cells is unaffected or only increased slightly by lithium substitution. 7. Thus, the primary mechanism of transmission block by lithium appears to be decreased transmitter release and inexcitability of presynaptic terminals, probably as a result of intracellular accumulation of lithium."}
{"id": "PMID:212501", "title": "Assignment of the receptor for ecotropic murine leukemia virus to mouse chromosome 5.", "content": "The gene for the receptor for ecotropic murine leukemia virus (Rev) has been assigned to mouse chromosome 5. This determination was made possible by an analysis of somatic cell hybrids between mouse and Chinese hamster cells. The parents of these hybrids were A/HeJ or Mus poschiavinus peritoneal exudate cells or BALB/c primary embryo fibroblasts and E36, a Chinese hamster lung fibroblast deficient in hypoxanthine guanine phosphoribosyltransferase. Segregation of mouse chromosomes in these hybrids was analyzed by chromosome banding and isozyme expression. Cells were tested for their ability to absorb and replicate vesicular stomatitis virus (murine leukemia virus [MuLV]) pseudotype particles and ecotropic MuLV as measured by the XC test. The presence of chromosome 5 was essential for receptor expression as determined by three statistical procedures. Segregation of the receptor for ecotropic murine leukemia virus was also followed in two series of subclones. In both, receptor expression was syntenic with phosphoglucomutase-1, an isozyme which has been mapped to mouse chromosome 5.", "contents": "Assignment of the receptor for ecotropic murine leukemia virus to mouse chromosome 5. The gene for the receptor for ecotropic murine leukemia virus (Rev) has been assigned to mouse chromosome 5. This determination was made possible by an analysis of somatic cell hybrids between mouse and Chinese hamster cells. The parents of these hybrids were A/HeJ or Mus poschiavinus peritoneal exudate cells or BALB/c primary embryo fibroblasts and E36, a Chinese hamster lung fibroblast deficient in hypoxanthine guanine phosphoribosyltransferase. Segregation of mouse chromosomes in these hybrids was analyzed by chromosome banding and isozyme expression. Cells were tested for their ability to absorb and replicate vesicular stomatitis virus (murine leukemia virus [MuLV]) pseudotype particles and ecotropic MuLV as measured by the XC test. The presence of chromosome 5 was essential for receptor expression as determined by three statistical procedures. Segregation of the receptor for ecotropic murine leukemia virus was also followed in two series of subclones. In both, receptor expression was syntenic with phosphoglucomutase-1, an isozyme which has been mapped to mouse chromosome 5."}
{"id": "PMID:212502", "title": "Ethylene formation by polymorphonuclear leukocytes. Role of myeloperoxidase.", "content": "Ethylene formation from the thioethers, beta-methylthiopropionaldehyde (methional) and 2-keto-4-thiomethylbutyric acid by phagocytosing polymorphonuclear leukocytes (PMNs) was found to be largely dependent on myeloperoxidase (MPO). Conversion was less than 10% of normal when MPO-deficient PMNs were employed; formation by normal PMNs was inhibited by the peroxidase inhibitors, azide, and cyanide, and a model system consisting of MPO, H2O2, chloride (or bromide) and EDTA was found which shared many of the properties of the predominant PMN system. MPO-independent mechanisms of ethylene formation were also identified. Ethylene formation from methional by phagocytosing eosinophils and by H2O2 in the presence or absence of catalase was stimulated by azide. The presence of MPO-independent, azide-stimulable systems in the PMN preparations was suggested by the azide stimulation of ethylene formation from methional when MPO-deficient leukocytes were employed. Ethylene formation by dye-sensitized photooxidation was also demonstrated and evidence obtained for the involvement of singlet oxygen (1O2). These findings are discussed in relation to the participation of H2O2, hydroxyl radicals, the superoxide anion and 1O2 in the formation of ethylene by PMNs and by the MPO model system.", "contents": "Ethylene formation by polymorphonuclear leukocytes. Role of myeloperoxidase. Ethylene formation from the thioethers, beta-methylthiopropionaldehyde (methional) and 2-keto-4-thiomethylbutyric acid by phagocytosing polymorphonuclear leukocytes (PMNs) was found to be largely dependent on myeloperoxidase (MPO). Conversion was less than 10% of normal when MPO-deficient PMNs were employed; formation by normal PMNs was inhibited by the peroxidase inhibitors, azide, and cyanide, and a model system consisting of MPO, H2O2, chloride (or bromide) and EDTA was found which shared many of the properties of the predominant PMN system. MPO-independent mechanisms of ethylene formation were also identified. Ethylene formation from methional by phagocytosing eosinophils and by H2O2 in the presence or absence of catalase was stimulated by azide. The presence of MPO-independent, azide-stimulable systems in the PMN preparations was suggested by the azide stimulation of ethylene formation from methional when MPO-deficient leukocytes were employed. Ethylene formation by dye-sensitized photooxidation was also demonstrated and evidence obtained for the involvement of singlet oxygen (1O2). These findings are discussed in relation to the participation of H2O2, hydroxyl radicals, the superoxide anion and 1O2 in the formation of ethylene by PMNs and by the MPO model system."}
{"id": "PMID:212503", "title": "Ir-genes in H-2 regulate generation of anti-viral cytotoxic T cells. Mapping to K or D and dominance of unresponsiveness.", "content": "H-2 dependent and virus-specific Ir genes regulate the generation of primary virus-specific K or D restricted cytotoxic T-cell responses in vivo. The following examples have been analyzed in some detail: first, Dk restricted responses to vaccinia in Sendai viruses are at least 30 times lower than the corresponding K-restricted responses irrespective of the H-2 haplotypes (k, b, d, dxs, dxq) of K and I regions; in contrast, LCMV infection generates high responses to Dk. These findings are consistent with but do not prove that this Ir gene maps to D. Second, Db restricted responses to vaccinia and Sendai viruses are high in strains possessing the Kq or KbIb, KbaIb haplotype, are very low in strains with Kk, and relatively low in mouse strains of the KdI-Ad haplotype; LCMV generates high Db restricted response in the presence of Kk. This Ir gene for the response to vaccinia and Sendai viruses maps to K since B10.BYR (KqIkdDb) is a responder and B10.A (2R) is a nonresponder (KkIkdDb). Third, virus and K or D allele specific nonresponsiveness is dominant with variable penetrance; in heterozygous mice the nonresponder Kk allele over-rides responsiveness normally found in KbDb or KqDb combinations. Fourth, when (responder X nonresponder)F1 lymphocytes are stimulated in an environment expressing vaccinia virus plus only a high responder Kb or Kq allelle and Db, response to vaccinia Db is high; in contrast when the same F1 cells are stimulated in an environment expressing the low responder allele Kk, response to vaccinia Db is low. Thus absence of Kk during immunization allows generation of high responsive Db restricted vaccinia specific cytotoxic T cells. The Dk dependent low response to vaccinia Dk can be explained by a preclusion rule or by failure of vaccinia to complex with Db; however the analysis of Kk dependent low response to vaccinia Db does not support these explanations or that self-tolerance is responsible for this Ir effect but is compatible with the interpretation that Kk vaccinia is immunodominant over Db vaccinia. These results are discussed with respect to (a) possible mechanisms of regulation by Ir genes and (b) H-2 polymorphism and HLA-disease association.", "contents": "Ir-genes in H-2 regulate generation of anti-viral cytotoxic T cells. Mapping to K or D and dominance of unresponsiveness. H-2 dependent and virus-specific Ir genes regulate the generation of primary virus-specific K or D restricted cytotoxic T-cell responses in vivo. The following examples have been analyzed in some detail: first, Dk restricted responses to vaccinia in Sendai viruses are at least 30 times lower than the corresponding K-restricted responses irrespective of the H-2 haplotypes (k, b, d, dxs, dxq) of K and I regions; in contrast, LCMV infection generates high responses to Dk. These findings are consistent with but do not prove that this Ir gene maps to D. Second, Db restricted responses to vaccinia and Sendai viruses are high in strains possessing the Kq or KbIb, KbaIb haplotype, are very low in strains with Kk, and relatively low in mouse strains of the KdI-Ad haplotype; LCMV generates high Db restricted response in the presence of Kk. This Ir gene for the response to vaccinia and Sendai viruses maps to K since B10.BYR (KqIkdDb) is a responder and B10.A (2R) is a nonresponder (KkIkdDb). Third, virus and K or D allele specific nonresponsiveness is dominant with variable penetrance; in heterozygous mice the nonresponder Kk allele over-rides responsiveness normally found in KbDb or KqDb combinations. Fourth, when (responder X nonresponder)F1 lymphocytes are stimulated in an environment expressing vaccinia virus plus only a high responder Kb or Kq allelle and Db, response to vaccinia Db is high; in contrast when the same F1 cells are stimulated in an environment expressing the low responder allele Kk, response to vaccinia Db is low. Thus absence of Kk during immunization allows generation of high responsive Db restricted vaccinia specific cytotoxic T cells. The Dk dependent low response to vaccinia Dk can be explained by a preclusion rule or by failure of vaccinia to complex with Db; however the analysis of Kk dependent low response to vaccinia Db does not support these explanations or that self-tolerance is responsible for this Ir effect but is compatible with the interpretation that Kk vaccinia is immunodominant over Db vaccinia. These results are discussed with respect to (a) possible mechanisms of regulation by Ir genes and (b) H-2 polymorphism and HLA-disease association."}
{"id": "PMID:212504", "title": "Helper-independent mink cell focus-inducing strains of Friend murine type-C virus: potential relationship to the origin of replication-defective spleen focus-forming virus.", "content": "Recent studies have indicated that both the replication-defective spleen focus-forming virus (SFFV) in the Friend virus complex and the helper-independent mink cell focus-inducing (MCF) viruses derived from AKR-murine leukemia virus (MuLV) are env gene recombinants between ecotropic virus and xenotropic virus. In an attempt to isolate additional env gene recombinants between Friend murine leukemia virus (F-MuLV) and xenotropic virus, we have inoculated cloned ecotropic F-MuLV into newborn NIH Swiss mice and analyzed MuLV released from preleukemic and leukemic spleens of infected mice. Two helper-independent MCF strains of F-MuLV have been isolated. Like the previously described AKR-MCF viruses, the Friend MCF viruses are env gene recombinants between an ecotropic virus (F-MuLV) and a mouse xenotropic virus, as shown by host range, interference pattern, and tryptic peptide analysis of the gp70s of these MuLV. Furthermore, RNA from the Friend MCF viruses hybridizes completely to cDNAsffv, a nucleic acid probe which detects that portion of SFFV which was not derived from P-MuLV. The ability to isolate replicating MCF viruses derived from F-MuLV FURTHER strengthens the parallels between the Friend erythroleukemia system and the AKR thymic leukemia system. Finally, the potential relationship of helper-independent env gene recombinants between F-MuLV and xenotropic virus to be highly leukemogenic SFFV is discussed.", "contents": "Helper-independent mink cell focus-inducing strains of Friend murine type-C virus: potential relationship to the origin of replication-defective spleen focus-forming virus. Recent studies have indicated that both the replication-defective spleen focus-forming virus (SFFV) in the Friend virus complex and the helper-independent mink cell focus-inducing (MCF) viruses derived from AKR-murine leukemia virus (MuLV) are env gene recombinants between ecotropic virus and xenotropic virus. In an attempt to isolate additional env gene recombinants between Friend murine leukemia virus (F-MuLV) and xenotropic virus, we have inoculated cloned ecotropic F-MuLV into newborn NIH Swiss mice and analyzed MuLV released from preleukemic and leukemic spleens of infected mice. Two helper-independent MCF strains of F-MuLV have been isolated. Like the previously described AKR-MCF viruses, the Friend MCF viruses are env gene recombinants between an ecotropic virus (F-MuLV) and a mouse xenotropic virus, as shown by host range, interference pattern, and tryptic peptide analysis of the gp70s of these MuLV. Furthermore, RNA from the Friend MCF viruses hybridizes completely to cDNAsffv, a nucleic acid probe which detects that portion of SFFV which was not derived from P-MuLV. The ability to isolate replicating MCF viruses derived from F-MuLV FURTHER strengthens the parallels between the Friend erythroleukemia system and the AKR thymic leukemia system. Finally, the potential relationship of helper-independent env gene recombinants between F-MuLV and xenotropic virus to be highly leukemogenic SFFV is discussed."}
{"id": "PMID:212505", "title": "Source and hormone-dependence of Gix-gp70 in mouse serum.", "content": "The gp70 family of glycoproteins is distinguished by the role of these molecules as constituents of C-type viral envelopes and also as Mendelian cellular constituents expressed independently of virus production. The source of G(IX)-gp70 in the serum of 129 strain mice, which are not overt producers of virus, could not be traced to any organ or tissue that is known to be G(IX)-positive by serological tests. Hematopoietic tissues were excluded as source of serum G(IX)-gp70 by tests with reciprocal radiation chimeras made from 129 and 129-G(IX)(-) donors and recipients. Thymus and spleen were excluded because excision of these organs did not affect levels of G(IX)-gp70 in the serum. The serum of young adult 129 males contains roughly four times as much G(IX)-gp70 as adult 129 females and the levels rise in both sexes with increasing age. Castration of 129 males reduced the level of serum G(IX)-gp70 to that of females, and the level was fully restored by testosterone. Thus the epididymis and seminal fluid, though rich in G(IX)-gp70, do not contribute significant amounts of G(IX)-gp70 to the serum. The level of G(IX)-gp70 in the serum of testosterone-treated females, though more than double that of untreated females, did not reach the level of normal males, under the conditions tested. This may signify that G(IX)-gp70 production by males is subject to imprinting by testosterone in early life. Evidently the main source of serum G(IX)-gp70 is a tissue or organ that is common to males and females, is directly or indirectly responsive to testosterone, and has not so far been identified serologically as G(IX)- positive.", "contents": "Source and hormone-dependence of Gix-gp70 in mouse serum. The gp70 family of glycoproteins is distinguished by the role of these molecules as constituents of C-type viral envelopes and also as Mendelian cellular constituents expressed independently of virus production. The source of G(IX)-gp70 in the serum of 129 strain mice, which are not overt producers of virus, could not be traced to any organ or tissue that is known to be G(IX)-positive by serological tests. Hematopoietic tissues were excluded as source of serum G(IX)-gp70 by tests with reciprocal radiation chimeras made from 129 and 129-G(IX)(-) donors and recipients. Thymus and spleen were excluded because excision of these organs did not affect levels of G(IX)-gp70 in the serum. The serum of young adult 129 males contains roughly four times as much G(IX)-gp70 as adult 129 females and the levels rise in both sexes with increasing age. Castration of 129 males reduced the level of serum G(IX)-gp70 to that of females, and the level was fully restored by testosterone. Thus the epididymis and seminal fluid, though rich in G(IX)-gp70, do not contribute significant amounts of G(IX)-gp70 to the serum. The level of G(IX)-gp70 in the serum of testosterone-treated females, though more than double that of untreated females, did not reach the level of normal males, under the conditions tested. This may signify that G(IX)-gp70 production by males is subject to imprinting by testosterone in early life. Evidently the main source of serum G(IX)-gp70 is a tissue or organ that is common to males and females, is directly or indirectly responsive to testosterone, and has not so far been identified serologically as G(IX)- positive."}
{"id": "PMID:212506", "title": "Virus-induced diabetes mellitus. XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with coxsackie virus B4.", "content": "Coxsackie virus B4 that had been passaged in cultures enriched for pancreatic beta cells produced a diabetes-like syndrome when inoculated into SJL/J mice. The infection resulted in insulitis and destruction of beta cells. Viral antigens were found in beta cells by staining with fluorescein-labeled antibody to Coxsackie virus B4. The destruction of beta cells led to a decrease in the immunoreactive insulin content of the pancreas and hypoinsulinemia. The reduction in immunoreactive insulin correlated inversely with the elevation of glucose in the blood and over 80% of the animals were found to be hyperglycemic within 14 days after infection. The percentage of animals with hyperglycemia decreased with time and at the end of 60 days, less than 5% of the animals were still hyperglycemic. However, many of the normoglycemic mice were found to be metabolically abnormal when evaluated by glucose tolerance tests. Studies on the susceptibility of the host showed that only certain inbred strains of mice became diabetic when infected with Coxsackie virus B4. It is concluded that both the passage history of the virus and the strain of the host influence the development of diabetes.", "contents": "Virus-induced diabetes mellitus. XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with coxsackie virus B4. Coxsackie virus B4 that had been passaged in cultures enriched for pancreatic beta cells produced a diabetes-like syndrome when inoculated into SJL/J mice. The infection resulted in insulitis and destruction of beta cells. Viral antigens were found in beta cells by staining with fluorescein-labeled antibody to Coxsackie virus B4. The destruction of beta cells led to a decrease in the immunoreactive insulin content of the pancreas and hypoinsulinemia. The reduction in immunoreactive insulin correlated inversely with the elevation of glucose in the blood and over 80% of the animals were found to be hyperglycemic within 14 days after infection. The percentage of animals with hyperglycemia decreased with time and at the end of 60 days, less than 5% of the animals were still hyperglycemic. However, many of the normoglycemic mice were found to be metabolically abnormal when evaluated by glucose tolerance tests. Studies on the susceptibility of the host showed that only certain inbred strains of mice became diabetic when infected with Coxsackie virus B4. It is concluded that both the passage history of the virus and the strain of the host influence the development of diabetes."}
{"id": "PMID:212507", "title": "Virus-replicating T cells in the immune response of mice. II. Characterization of T cells capable of replicating vesicular stomatitis virus.", "content": "Immunocytological properties of the splenic T cell (Tv) which develop into virus plaque-forming cells in response to the antigenic challenge in vitro were investigated in relation to the properties of helper T cells and suppressor T cells in antibody response. Tv was observed in spleen around 1 wk after the intravenous injection of mice with 10(7) sheep erythrocytes. This contrasted with the finding that both helper T cells and suppressor T cells developed as early as 3 days after the immunization. Tv was proliferative in response to the antigenic stimulation, whereas helper T-cell activity could be expressed without cell division. Development of Tv to virus plaque-forming cells was much more dependent on macrophages than the generation of helper activity. Tv was found in nylon wool adherent fraction, whereas helper T cell was found in both nylon adherent and nonadherent fractions. Tv belongs to the short-lived and nonrecirculating T-cell population (T1), whereas the major part of helper T cells belongs to the long-lived and recirculating T-cell population (T2). These results strongly suggest that vesicular stomatitis virus infect and replicate in the different subset(s) of T cell(s) to which the major part of helper T cells belong.", "contents": "Virus-replicating T cells in the immune response of mice. II. Characterization of T cells capable of replicating vesicular stomatitis virus. Immunocytological properties of the splenic T cell (Tv) which develop into virus plaque-forming cells in response to the antigenic challenge in vitro were investigated in relation to the properties of helper T cells and suppressor T cells in antibody response. Tv was observed in spleen around 1 wk after the intravenous injection of mice with 10(7) sheep erythrocytes. This contrasted with the finding that both helper T cells and suppressor T cells developed as early as 3 days after the immunization. Tv was proliferative in response to the antigenic stimulation, whereas helper T-cell activity could be expressed without cell division. Development of Tv to virus plaque-forming cells was much more dependent on macrophages than the generation of helper activity. Tv was found in nylon wool adherent fraction, whereas helper T cell was found in both nylon adherent and nonadherent fractions. Tv belongs to the short-lived and nonrecirculating T-cell population (T1), whereas the major part of helper T cells belongs to the long-lived and recirculating T-cell population (T2). These results strongly suggest that vesicular stomatitis virus infect and replicate in the different subset(s) of T cell(s) to which the major part of helper T cells belong."}
{"id": "PMID:212508", "title": "Virus-replicating T cells in the immune response of mice. III. Role of vesicular stomatitis virus-replicating T cells in the antibody response.", "content": "The functional role of the T cell (Tv) which can replicate vesicular stomatitis virus (VSV) on activation by the antigen was investigated in antibody response in vitro. By the inoculation of VSV into the culture, marked augmentation of antibody response to sheep erythrocytes (SRBC) was observed in the culture of spleen cells taken more than 3 days after the immunization with SRBC, suggesting that the VSV-susceptible suppressor cells were included in these spleen cells and the activity was eliminated by the effect of VSV. Development of two distinct types of suppressor T cells was revealed in the spleen of mice after the priming with SRBC. First, nylon wool nonadherent (NAd) suppressor T cells found in the spleen cells taken 3 days after immunization, and second, nylon wool adherent (Ad) suppressor T cells found in the spleen cells taken approximately 1 wk after immunization. The activity of nylon Ad suppressor T cells was completely abolished by VSV-preinfection, whereas that of nylon NAd suppressor T cells was unaffected. It was also shown that the helper T-cell activity was not influenced by VSV-preinfection. These results provided direct evidence that nylon Ad suppressor T cell but not nylon NAd suppressor T cell nor helper T cell can actually replicate VSV after antigenic stimulation. Thus it was strongly suggested that Tv represents the nylon Ad suppressor T cells.", "contents": "Virus-replicating T cells in the immune response of mice. III. Role of vesicular stomatitis virus-replicating T cells in the antibody response. The functional role of the T cell (Tv) which can replicate vesicular stomatitis virus (VSV) on activation by the antigen was investigated in antibody response in vitro. By the inoculation of VSV into the culture, marked augmentation of antibody response to sheep erythrocytes (SRBC) was observed in the culture of spleen cells taken more than 3 days after the immunization with SRBC, suggesting that the VSV-susceptible suppressor cells were included in these spleen cells and the activity was eliminated by the effect of VSV. Development of two distinct types of suppressor T cells was revealed in the spleen of mice after the priming with SRBC. First, nylon wool nonadherent (NAd) suppressor T cells found in the spleen cells taken 3 days after immunization, and second, nylon wool adherent (Ad) suppressor T cells found in the spleen cells taken approximately 1 wk after immunization. The activity of nylon Ad suppressor T cells was completely abolished by VSV-preinfection, whereas that of nylon NAd suppressor T cells was unaffected. It was also shown that the helper T-cell activity was not influenced by VSV-preinfection. These results provided direct evidence that nylon Ad suppressor T cell but not nylon NAd suppressor T cell nor helper T cell can actually replicate VSV after antigenic stimulation. Thus it was strongly suggested that Tv represents the nylon Ad suppressor T cells."}
{"id": "PMID:212509", "title": "Chronic pain: a review for the family physician.", "content": "The challenge of effective management of chronic pain frequently confronts the family physician. Successful management relies on the physician's skill in integrating fundamental concepts in the pathophysiology, psychodynamics, and diagnostic and therapeutic modalities associated with chronic pain syndromes. The use of time-contingent rather than pain-contingent therapy in the prevention of the chronic pain state is advocated.", "contents": "Chronic pain: a review for the family physician. The challenge of effective management of chronic pain frequently confronts the family physician. Successful management relies on the physician's skill in integrating fundamental concepts in the pathophysiology, psychodynamics, and diagnostic and therapeutic modalities associated with chronic pain syndromes. The use of time-contingent rather than pain-contingent therapy in the prevention of the chronic pain state is advocated."}
{"id": "PMID:212512", "title": "Suppression of interferon production in mouse spleen cells by cytochalasin D.", "content": "Cytochalasin D is thought to impair microfilament function. The present study has investigated its effects on four different systems in which interferon is formed, namely (1) mouse fibroblasts induced with virus (2) mouse spleen cells induced with virus, or (3) with endotoxin or (4) by allogeneic stimulation. Cytochalasin D did not suppress formation of interferon by fibroblasts (L cells) or spleen cells stimulated with either HVJ or NDV. However it did suppress production of interferon by spleen cells in response to endotoxin or an allogeneic stimulation; here its action was apparently not on the secretion of interferon, but on some earlier event. It also suppressed the production of interferon by mouse spleen cells induced with HVJ if this had been u.v. irradiated for more than 15 min: this suggests that cytochalasin D sensitive structures do play some role in interferon production by mouse spleen cells when stimulated with HVJ, as well as when they are stimulated with endotoxin or an allogeneic stimulus.", "contents": "Suppression of interferon production in mouse spleen cells by cytochalasin D. Cytochalasin D is thought to impair microfilament function. The present study has investigated its effects on four different systems in which interferon is formed, namely (1) mouse fibroblasts induced with virus (2) mouse spleen cells induced with virus, or (3) with endotoxin or (4) by allogeneic stimulation. Cytochalasin D did not suppress formation of interferon by fibroblasts (L cells) or spleen cells stimulated with either HVJ or NDV. However it did suppress production of interferon by spleen cells in response to endotoxin or an allogeneic stimulation; here its action was apparently not on the secretion of interferon, but on some earlier event. It also suppressed the production of interferon by mouse spleen cells induced with HVJ if this had been u.v. irradiated for more than 15 min: this suggests that cytochalasin D sensitive structures do play some role in interferon production by mouse spleen cells when stimulated with HVJ, as well as when they are stimulated with endotoxin or an allogeneic stimulus."}
{"id": "PMID:212513", "title": "The role of macrophages in mice infected with murine cytomegalovirus.", "content": "Quantitative studies were made of the infection of mouse peritoneal macrophages in vitro by cytomegalovirus, using virus assays and immunofluorescence. The efficiency of infection was low. Broth-induced peritoneal macrophages were about four times more resistant to infection than unstimulated macrophages and it was even more difficult to infect activated macrophages taken from mice 6 days after intravenous infection. Peritoneal macrophages (unstimulated) were infected at least 15 times more readily by tissue culture-passed (attenuated) virus than by salivary gland (virulent) virus, but macrophages prevented the spread of tissue culture virus to underlying susceptible mouse embryo fibroblasts, whereas they did so much less effectively with virulent salivary gland virus. The pathogenesis of infection was studied in intact mice by immunofluorescence, and the observations paralleled the in vitro findings. When large doses of salivary gland virus were injected intravenously, infected Kupffer cells (liver macrophages) were occasionally seen and the inoculated virus directly infected large numbers of hepatic cells. In similar experiments with tissue culture-passed virus, there was initial infection of occasional Kupffer cells, which only rarely gave rise to infected hepatic cells. Differences in the extend of Kupffer cell infection by the two strains of virus were not detected in these experiments. Salivary gland virus also usually failed to infect splenic or lymph node macrophages. Occasional infected mononuclear cells were seen in the blood, lung and bone marrow, but were not identified. Infected cells were very rarely seen in the thymus, even in suckling mice.", "contents": "The role of macrophages in mice infected with murine cytomegalovirus. Quantitative studies were made of the infection of mouse peritoneal macrophages in vitro by cytomegalovirus, using virus assays and immunofluorescence. The efficiency of infection was low. Broth-induced peritoneal macrophages were about four times more resistant to infection than unstimulated macrophages and it was even more difficult to infect activated macrophages taken from mice 6 days after intravenous infection. Peritoneal macrophages (unstimulated) were infected at least 15 times more readily by tissue culture-passed (attenuated) virus than by salivary gland (virulent) virus, but macrophages prevented the spread of tissue culture virus to underlying susceptible mouse embryo fibroblasts, whereas they did so much less effectively with virulent salivary gland virus. The pathogenesis of infection was studied in intact mice by immunofluorescence, and the observations paralleled the in vitro findings. When large doses of salivary gland virus were injected intravenously, infected Kupffer cells (liver macrophages) were occasionally seen and the inoculated virus directly infected large numbers of hepatic cells. In similar experiments with tissue culture-passed virus, there was initial infection of occasional Kupffer cells, which only rarely gave rise to infected hepatic cells. Differences in the extend of Kupffer cell infection by the two strains of virus were not detected in these experiments. Salivary gland virus also usually failed to infect splenic or lymph node macrophages. Occasional infected mononuclear cells were seen in the blood, lung and bone marrow, but were not identified. Infected cells were very rarely seen in the thymus, even in suckling mice."}
{"id": "PMID:212514", "title": "Comparison of interferon action in interferon resistant and sensitive L1210 cells.", "content": "Translation inhibition, leu-tRNA aminoacylation and double-stranded RNA and ATP dependent phosphorylation were examined in interferon-treated and control cell-free lysates of leukaemic mouse L 1210 R and L 1210 S cells. No differences were observed between the respective interferon-treated and control cell-free extracts, except for the presence of an enhanced 67K dalton phosphoprotein fraction in interferon-treated L 1210 S cell-free extracts. In non-responding cell-free lysates, the lack of stimulation of a 67K dalton phosphoprotein fraction cannot be explained by the presence of an increased level of some inhibitory activity, such as a phosphatase.", "contents": "Comparison of interferon action in interferon resistant and sensitive L1210 cells. Translation inhibition, leu-tRNA aminoacylation and double-stranded RNA and ATP dependent phosphorylation were examined in interferon-treated and control cell-free lysates of leukaemic mouse L 1210 R and L 1210 S cells. No differences were observed between the respective interferon-treated and control cell-free extracts, except for the presence of an enhanced 67K dalton phosphoprotein fraction in interferon-treated L 1210 S cell-free extracts. In non-responding cell-free lysates, the lack of stimulation of a 67K dalton phosphoprotein fraction cannot be explained by the presence of an increased level of some inhibitory activity, such as a phosphatase."}
{"id": "PMID:212515", "title": "Optical diffraction analysis of electron microscope images of tubular structures found in cells infected with herpes simplex virus type 2.", "content": "Optical diffraction analysis was done on the electron micrographs of tubular structures found in cells infected with herpes simplex virus type 2. By this method, the helical arrangement of subunits forming a tubular structure was demonstrated.", "contents": "Optical diffraction analysis of electron microscope images of tubular structures found in cells infected with herpes simplex virus type 2. Optical diffraction analysis was done on the electron micrographs of tubular structures found in cells infected with herpes simplex virus type 2. By this method, the helical arrangement of subunits forming a tubular structure was demonstrated."}
{"id": "PMID:212516", "title": "Tumour specific transplantation antigen in hamster tumour cells induced with BK virus.", "content": "Immunization of hamsters with purified BK virus (BKV) followed by transplantation of BKV-induced hamster tumour cells revealed a tumour specific transplantation antigen (TSTA) in these cells. The antigen did not cross-react with the TSTA of SV40 since immunization with BKV did not protect against challenge of SV40 tumour cells.", "contents": "Tumour specific transplantation antigen in hamster tumour cells induced with BK virus. Immunization of hamsters with purified BK virus (BKV) followed by transplantation of BKV-induced hamster tumour cells revealed a tumour specific transplantation antigen (TSTA) in these cells. The antigen did not cross-react with the TSTA of SV40 since immunization with BKV did not protect against challenge of SV40 tumour cells."}
{"id": "PMID:212517", "title": "Mink lung cells: a non-primate cell line highly susceptible for varicella-zoster virus.", "content": "Mink lung cells (MvILu) are highly susceptible to varicella-zoster virus (VZV). The titres of cell-free VZV suspensions reached 1.0 x 10(7) p.f.u./ml at 3 days post-infection, with subsequent cell degeneration, if MvILu cells were infected with a multiplicity of infectious virus of 0.01 p.f.u./cell. In contrast, during the same period and under the same conditions the titres of cell-free VZV were 10(2) to 10(3) times lower when grown on human foreskin fibroblasts. A fast and reliable plaque assay and a neutralization test for VZV on MvILU cells, were developed.", "contents": "Mink lung cells: a non-primate cell line highly susceptible for varicella-zoster virus. Mink lung cells (MvILu) are highly susceptible to varicella-zoster virus (VZV). The titres of cell-free VZV suspensions reached 1.0 x 10(7) p.f.u./ml at 3 days post-infection, with subsequent cell degeneration, if MvILu cells were infected with a multiplicity of infectious virus of 0.01 p.f.u./cell. In contrast, during the same period and under the same conditions the titres of cell-free VZV were 10(2) to 10(3) times lower when grown on human foreskin fibroblasts. A fast and reliable plaque assay and a neutralization test for VZV on MvILU cells, were developed."}
{"id": "PMID:212518", "title": "Structural polypeptides of Machupo virus.", "content": "The structural proteins of an arenavirus pathogen, Machupo virus, were compared to the structural proteins of two previously characterized non-pathogenic arenaviruses, Pichinde and Tacaribe, in SDS-polyacrylamide gels. Similarities in mol. wt. of the major structural proteins from both pathogenic and non-pathogenic viruses were apparent; however, some differences in the number of glycosylation properties of minor proteins were observed. Machupo virions contain two major protein species. The most prominent is a non-glycosylated protein with a mol. wt. of 68000, while the other was glycosylated protein with a mol. wt. of 41000. Minor amounts of other proteins (mol. wt. 84000, 74000, 50000 and 15000) and a glycolipid were also observed.", "contents": "Structural polypeptides of Machupo virus. The structural proteins of an arenavirus pathogen, Machupo virus, were compared to the structural proteins of two previously characterized non-pathogenic arenaviruses, Pichinde and Tacaribe, in SDS-polyacrylamide gels. Similarities in mol. wt. of the major structural proteins from both pathogenic and non-pathogenic viruses were apparent; however, some differences in the number of glycosylation properties of minor proteins were observed. Machupo virions contain two major protein species. The most prominent is a non-glycosylated protein with a mol. wt. of 68000, while the other was glycosylated protein with a mol. wt. of 41000. Minor amounts of other proteins (mol. wt. 84000, 74000, 50000 and 15000) and a glycolipid were also observed."}
{"id": "PMID:212519", "title": "Induction of infectious virus DNA and virus particles by mitomycin C in SV40-transformed mouse cells.", "content": "A line of SV40-transformed mouse cells (SV/3T3-4E) was isolated and four clones were derived from this line. Spontaneous production of small amounts of infectious SV40 DNA was detected in the parental line and in three out of the four clones tested, although no synthesis of virions could be demonstrated. The yields of SV40 DNA were significantly enhanced following treatment of these cells with mitomycin C and infectious virus particles became detectable occasionally.", "contents": "Induction of infectious virus DNA and virus particles by mitomycin C in SV40-transformed mouse cells. A line of SV40-transformed mouse cells (SV/3T3-4E) was isolated and four clones were derived from this line. Spontaneous production of small amounts of infectious SV40 DNA was detected in the parental line and in three out of the four clones tested, although no synthesis of virions could be demonstrated. The yields of SV40 DNA were significantly enhanced following treatment of these cells with mitomycin C and infectious virus particles became detectable occasionally."}
{"id": "PMID:212520", "title": "Suppression of the synthesis of cellular macromolecules by herpes simplex virus.", "content": "Synthesis of cellular protein was substantially inhibited within 1 h of infection with herpes simplex virus, type 2, strain G (HSV-2). The inhibition also occurred, although no virus-specific protein synthesis was detected, after infection with u.v. irradiated virus and in cytoplasts that had been enucleated before infection. The inhibitory activity could not be distinguished from infectivity by dilution, sedimentation or reaction with gamma-globulin. HSV-2 also suppresssed the synthesis of Sendai virus proteins, but not those specified by HSV-1. Host protein synthesis was no more sensitive than virus protein synthesis to an increased concentration of NaCl in the medium, nor could the suppression of host synthesis be prevented by adding excess MgCl2 to the medium or by omitting CaCl2 or NaCl. It was accompanied by the breakdown of polyribosomes, which also occurred in the presence of cycloheximide but not at 4 degrees C. The breakdown yielded ribosomes that were sensitive to a high salt concentration, unlike those produced by treatment of polyribosomes with RNase. The synthesis of cellular DNA and RNA was also inhibited following infection with u.v.-inactivated virus. It is concluded that the suppression of host protein synthesis (and probably also of host DNA and RNA synthesis) is caused by a constituent of the infecting virus particles. The mechanism is obscure but probably does not depend on the leakage out of the cell of Mg2+ or into the cell or Ca2+ or Na+ ions, nor on the specific inhibition of initiation of host polypeptide chains, nor on RNase-like attack on host polyribosomes.", "contents": "Suppression of the synthesis of cellular macromolecules by herpes simplex virus. Synthesis of cellular protein was substantially inhibited within 1 h of infection with herpes simplex virus, type 2, strain G (HSV-2). The inhibition also occurred, although no virus-specific protein synthesis was detected, after infection with u.v. irradiated virus and in cytoplasts that had been enucleated before infection. The inhibitory activity could not be distinguished from infectivity by dilution, sedimentation or reaction with gamma-globulin. HSV-2 also suppresssed the synthesis of Sendai virus proteins, but not those specified by HSV-1. Host protein synthesis was no more sensitive than virus protein synthesis to an increased concentration of NaCl in the medium, nor could the suppression of host synthesis be prevented by adding excess MgCl2 to the medium or by omitting CaCl2 or NaCl. It was accompanied by the breakdown of polyribosomes, which also occurred in the presence of cycloheximide but not at 4 degrees C. The breakdown yielded ribosomes that were sensitive to a high salt concentration, unlike those produced by treatment of polyribosomes with RNase. The synthesis of cellular DNA and RNA was also inhibited following infection with u.v.-inactivated virus. It is concluded that the suppression of host protein synthesis (and probably also of host DNA and RNA synthesis) is caused by a constituent of the infecting virus particles. The mechanism is obscure but probably does not depend on the leakage out of the cell of Mg2+ or into the cell or Ca2+ or Na+ ions, nor on the specific inhibition of initiation of host polypeptide chains, nor on RNase-like attack on host polyribosomes."}
{"id": "PMID:212521", "title": "Prostanglandins enhance spread of herpes simplex virus in cell cultures.", "content": "Stimuli such as u.v. light or trauma which induce recurrence of herpes simplex may act by affecting virus replication in the skin. Such stimuli release pharmacologically active agents in the skin, including prostaglandins (PGs) such as PGE2. These agents, and other compounds which alter levels of adenosine cyclic monophosphate (cyclic AMP), were tested for their effect on the replication of herpes simplex virus (HSV) in Vero cells. Prostanglandin E2 (PGE2) and prostaglandin F2alpha both increase the size of HSV plaques; PGE2 also increases the yield of virus inoculated at low m.o.i. Moreover, inhibitors of prostanglandin synthesis decrease plaque size and inhibit the growth of virus inoculated at low m.o.i.; such inhibition can be partially overcome by adding PGE2. Analysis of the results suggest that prostaglandins can enhance cell-to-cell spread of HSV, but that cyclic AMP is probably not involved in this effect.", "contents": "Prostanglandins enhance spread of herpes simplex virus in cell cultures. Stimuli such as u.v. light or trauma which induce recurrence of herpes simplex may act by affecting virus replication in the skin. Such stimuli release pharmacologically active agents in the skin, including prostaglandins (PGs) such as PGE2. These agents, and other compounds which alter levels of adenosine cyclic monophosphate (cyclic AMP), were tested for their effect on the replication of herpes simplex virus (HSV) in Vero cells. Prostanglandin E2 (PGE2) and prostaglandin F2alpha both increase the size of HSV plaques; PGE2 also increases the yield of virus inoculated at low m.o.i. Moreover, inhibitors of prostanglandin synthesis decrease plaque size and inhibit the growth of virus inoculated at low m.o.i.; such inhibition can be partially overcome by adding PGE2. Analysis of the results suggest that prostaglandins can enhance cell-to-cell spread of HSV, but that cyclic AMP is probably not involved in this effect."}
{"id": "PMID:212522", "title": "Protection of mice against viral infection by Corynebacterium parvum and Bordetella pertussis.", "content": "Mice could be significantly protected against infection with herpes simplex virus (HSV) by i.p. or i.v. injection of killed Corynebacterium parvum 7 days before infection. This protection was seen in inbred strains of mice with a different degree of sensitivity to HSV and after both i.p. and i.v. infection. Resistant mice immunosuppressed by X-irradiation and showing an increased susceptibility to HSV could also be protected by a previous injection of C. parvum. Elevated levels of interferon were demonstrated in the serum of mice injected with C. parvum 5 to 12 days previously. Four different strains of anaerobic coryneforms were compared and only those which were able to induce a systemic activation of the lymphoreticular system (as reflected by splenomegaly) protected against HSV infection. Protection against HSV-infection could also be demonstrated by using killed Bordetella pertussis. C. parvum also protected against Semliki Forest virus infection in two different strains of mice.", "contents": "Protection of mice against viral infection by Corynebacterium parvum and Bordetella pertussis. Mice could be significantly protected against infection with herpes simplex virus (HSV) by i.p. or i.v. injection of killed Corynebacterium parvum 7 days before infection. This protection was seen in inbred strains of mice with a different degree of sensitivity to HSV and after both i.p. and i.v. infection. Resistant mice immunosuppressed by X-irradiation and showing an increased susceptibility to HSV could also be protected by a previous injection of C. parvum. Elevated levels of interferon were demonstrated in the serum of mice injected with C. parvum 5 to 12 days previously. Four different strains of anaerobic coryneforms were compared and only those which were able to induce a systemic activation of the lymphoreticular system (as reflected by splenomegaly) protected against HSV infection. Protection against HSV-infection could also be demonstrated by using killed Bordetella pertussis. C. parvum also protected against Semliki Forest virus infection in two different strains of mice."}
{"id": "PMID:212523", "title": "Detection of Epstein-Barr virus antigens and antibodies by peroxidase-labeled specific immunoglobulins.", "content": "Detection of the Epstein-Barr (EBV) antigens, early antigen (EA), viral capsid antigen (VCA), and nuclear antigen (EBNA) by the indirect immunoperoxidase technique was highly sensitive. Antibody titers to EBNA, EA, and VCA were determined in more than 25 sera of patients with Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), or normal persons. A good correlation between the titers of these antigens was obtained by the immunoperoxidase and immunofluorescence methods. The indirect (anti-IgG) immunoperoxidase technique for the detection of EBNA is, in contrast to the indirect immunofluorescence method, highly sensitive. EBNA was associated with the chromosomes in cells arrested in the metaphase with colchicine.", "contents": "Detection of Epstein-Barr virus antigens and antibodies by peroxidase-labeled specific immunoglobulins. Detection of the Epstein-Barr (EBV) antigens, early antigen (EA), viral capsid antigen (VCA), and nuclear antigen (EBNA) by the indirect immunoperoxidase technique was highly sensitive. Antibody titers to EBNA, EA, and VCA were determined in more than 25 sera of patients with Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), or normal persons. A good correlation between the titers of these antigens was obtained by the immunoperoxidase and immunofluorescence methods. The indirect (anti-IgG) immunoperoxidase technique for the detection of EBNA is, in contrast to the indirect immunofluorescence method, highly sensitive. EBNA was associated with the chromosomes in cells arrested in the metaphase with colchicine."}
{"id": "PMID:212524", "title": "Thermal treatment and infectivity of hepatitis A virus in human feces.", "content": "The susceptibility of white-lipped marmoset monkeys (Saguinus sp) to human hepatitis A virus (HAV) provides a system for evaluation of thermal inactivation of HAV in feces and contaminated shellfish. Intramuscular or oral administration of HAV derived from feces of four patients with acute hepatitis A induced hepatitis in 28--100% of the inoculated marmosets. A 10% (w/v) fecal pool (GBG-BM) prepared from two patients (GBG and GBM) induced hepatitis in marmosets (2/4 with 1 ml; 2/2 with 3 ml) when given orally as a 1 : 3 dilution. A HAV-baby food raw oyster mixture fed to fasted marmosets induced hepatitis in 1/4 and seroconversion in 2/4 animals. Two groups of oysters were injected with HAV (concentrated 3 : 1 by centrifugation of the GBG-BM pool); one group was treated at 140 degrees F for 19 minutes and the other served as an untreated control. In animals fed the untreated inoculum, 4/6 developed hepatitis and 6/6 seroconverted, whereas of those fed the heat-treated inoculum 1/7 developed hepatitis and 2/7 seroconverted. These data suggest that pasteurization methods could be developed that would eliminate shellfish-associated hepatitis A and retain the palatability of the shellfish.", "contents": "Thermal treatment and infectivity of hepatitis A virus in human feces. The susceptibility of white-lipped marmoset monkeys (Saguinus sp) to human hepatitis A virus (HAV) provides a system for evaluation of thermal inactivation of HAV in feces and contaminated shellfish. Intramuscular or oral administration of HAV derived from feces of four patients with acute hepatitis A induced hepatitis in 28--100% of the inoculated marmosets. A 10% (w/v) fecal pool (GBG-BM) prepared from two patients (GBG and GBM) induced hepatitis in marmosets (2/4 with 1 ml; 2/2 with 3 ml) when given orally as a 1 : 3 dilution. A HAV-baby food raw oyster mixture fed to fasted marmosets induced hepatitis in 1/4 and seroconversion in 2/4 animals. Two groups of oysters were injected with HAV (concentrated 3 : 1 by centrifugation of the GBG-BM pool); one group was treated at 140 degrees F for 19 minutes and the other served as an untreated control. In animals fed the untreated inoculum, 4/6 developed hepatitis and 6/6 seroconverted, whereas of those fed the heat-treated inoculum 1/7 developed hepatitis and 2/7 seroconverted. These data suggest that pasteurization methods could be developed that would eliminate shellfish-associated hepatitis A and retain the palatability of the shellfish."}
{"id": "PMID:212525", "title": "Hepatitis B virus DNA in primary hepatocellular carcinoma tissue.", "content": "Tumour, cirrhotic, and metastatic tissues from four patients with primary hepatocellular carcinoma have been investigated for the presence of hepatitis B viral DNA by nucleic acid hybridization. Tumours from two of three patients with a current HBV infection contained 1--2 genomes per cell of unintegrated viral DNA, while tumours from the third HBs antigen-positive patient contained less than one genome equivalent per ten cells. A tumour from one patient with anti-HBs contained no detectable HBV DNA. A variety of models involving HBV as an etiologic agent may be advanced to explain the statistical correlation of HBV infection with primary hepatocellular carcinoma (PHC). The data presented here argue against the model that HBV DNA integrated into every cell is required to maintain the oncogenic transformation of hepatocytes, but they do not rule out other models.", "contents": "Hepatitis B virus DNA in primary hepatocellular carcinoma tissue. Tumour, cirrhotic, and metastatic tissues from four patients with primary hepatocellular carcinoma have been investigated for the presence of hepatitis B viral DNA by nucleic acid hybridization. Tumours from two of three patients with a current HBV infection contained 1--2 genomes per cell of unintegrated viral DNA, while tumours from the third HBs antigen-positive patient contained less than one genome equivalent per ten cells. A tumour from one patient with anti-HBs contained no detectable HBV DNA. A variety of models involving HBV as an etiologic agent may be advanced to explain the statistical correlation of HBV infection with primary hepatocellular carcinoma (PHC). The data presented here argue against the model that HBV DNA integrated into every cell is required to maintain the oncogenic transformation of hepatocytes, but they do not rule out other models."}
{"id": "PMID:212527", "title": "Effects of phosphonoacetic acid on subacute myeloopticoneuropathy virus in vitro and in vivo.", "content": "The effect of phosphonoacetic acid (PAA) in vitro and in vivo on subacute myeloopticoneuropathy (SMON) virus isolated from the spinal fluid of SMON patients was studied. PAA inhibited multiplication of SMON virus in cultures, but it did not show a direct effect on the virus. The drug did not influence the disease when the medication was started from 10 days after infection of suckling mice. However, the drug did elicit a delay in the incubation period.", "contents": "Effects of phosphonoacetic acid on subacute myeloopticoneuropathy virus in vitro and in vivo. The effect of phosphonoacetic acid (PAA) in vitro and in vivo on subacute myeloopticoneuropathy (SMON) virus isolated from the spinal fluid of SMON patients was studied. PAA inhibited multiplication of SMON virus in cultures, but it did not show a direct effect on the virus. The drug did not influence the disease when the medication was started from 10 days after infection of suckling mice. However, the drug did elicit a delay in the incubation period."}
{"id": "PMID:212528", "title": "Steroid hormone alteration of herpes simplex virus type 1 replication.", "content": "The effect of steroid hormones on herpes simplex virus type 1 replication was examined. Virus replication studies revealed that various concentrations of prednisolone, hydrocortisone, dexamethasone, or progesterone could decrease virus yields up to a maximum of 99%. Using isopycnic centrifugation in CsCl to separate viral from cell DNA, it was found that virus-specific DNA synthesis was decreased by 30 to 100% depending on the hormone and concentration used. Cell-specific DNA synthesis was also adversely affected, but this did not alter cell viability or plating efficiency.", "contents": "Steroid hormone alteration of herpes simplex virus type 1 replication. The effect of steroid hormones on herpes simplex virus type 1 replication was examined. Virus replication studies revealed that various concentrations of prednisolone, hydrocortisone, dexamethasone, or progesterone could decrease virus yields up to a maximum of 99%. Using isopycnic centrifugation in CsCl to separate viral from cell DNA, it was found that virus-specific DNA synthesis was decreased by 30 to 100% depending on the hormone and concentration used. Cell-specific DNA synthesis was also adversely affected, but this did not alter cell viability or plating efficiency."}
{"id": "PMID:212529", "title": "Human rotavirus infection in infants and young children with intussusception.", "content": "Human rotavirus was detected by electron microscopy in 11 of 30 infants and young children with intussusception (37% of subjects under study). Serologic complement fixation tests revealed evidence of infection with the rotavirus in 70% of the patients examined who eliminated the rotavirus in their stools. These results indicate that human rotavirus, in addition to adenovirus, may be an infectious agent causing intussusception in infants and young children.", "contents": "Human rotavirus infection in infants and young children with intussusception. Human rotavirus was detected by electron microscopy in 11 of 30 infants and young children with intussusception (37% of subjects under study). Serologic complement fixation tests revealed evidence of infection with the rotavirus in 70% of the patients examined who eliminated the rotavirus in their stools. These results indicate that human rotavirus, in addition to adenovirus, may be an infectious agent causing intussusception in infants and young children."}
{"id": "PMID:212542", "title": "Homotransplantation of the liver in a patient with hepatoma and hereditary tyrosinemia.", "content": "A girl with hereditary tyrosinemia, diagnosed at 6 months of age, was treated with a diet restricted in phenylalanine and tyrosine. At 9 1/2 years of age she developed an acutely enlarged liver and spleen, and the diagnosis of hepatocarcinoma was made. The patient received a liver transplant and tyrosine metabolites became normal while she was receiving a regular diet. Three months later, an infected thrombosis of the portal vein caused her death. Liver transplant appears to be an effective method of enzyme replacement in tyrosinemia and should be considered for prevention of hepatoma.", "contents": "Homotransplantation of the liver in a patient with hepatoma and hereditary tyrosinemia. A girl with hereditary tyrosinemia, diagnosed at 6 months of age, was treated with a diet restricted in phenylalanine and tyrosine. At 9 1/2 years of age she developed an acutely enlarged liver and spleen, and the diagnosis of hepatocarcinoma was made. The patient received a liver transplant and tyrosine metabolites became normal while she was receiving a regular diet. Three months later, an infected thrombosis of the portal vein caused her death. Liver transplant appears to be an effective method of enzyme replacement in tyrosinemia and should be considered for prevention of hepatoma."}
{"id": "PMID:212545", "title": "The basis of beta adrenergic bronchodilation.", "content": "The effects of varying external K and Ca on isometric tension of the tracheal smooth muscle (TSM) of the dog were measured and the relaxant action of isoprenaline IPn) was noted in the same system. The results were similar to those reported for other smooth muscles. Oxygen consumption of the TSM was measured by a reproducible semimicro method simultaneously with mechanical tension under various conditions as above. Depolarized TSM required the energy equivalent of about 0.005 microliter of O2 min -1 . g -1 . t-1 (t = tension in g. cm-2) for sustained contraction. Relaxation of the depolarized TSM by IPn apparently was due to the antagonism of Ca and required extra energy equal to over half that required for contraction. Dibutyryl cyclic adenosine monophosphate failed to relax the depolarized TSM while tissue cyclic adenosine monophosphate level was raised by exposure to IPn. The subcellular energy consuming processes by which IPn antagonizes the contractile effect of Ca in depolarized TSM require further investigation.", "contents": "The basis of beta adrenergic bronchodilation. The effects of varying external K and Ca on isometric tension of the tracheal smooth muscle (TSM) of the dog were measured and the relaxant action of isoprenaline IPn) was noted in the same system. The results were similar to those reported for other smooth muscles. Oxygen consumption of the TSM was measured by a reproducible semimicro method simultaneously with mechanical tension under various conditions as above. Depolarized TSM required the energy equivalent of about 0.005 microliter of O2 min -1 . g -1 . t-1 (t = tension in g. cm-2) for sustained contraction. Relaxation of the depolarized TSM by IPn apparently was due to the antagonism of Ca and required extra energy equal to over half that required for contraction. Dibutyryl cyclic adenosine monophosphate failed to relax the depolarized TSM while tissue cyclic adenosine monophosphate level was raised by exposure to IPn. The subcellular energy consuming processes by which IPn antagonizes the contractile effect of Ca in depolarized TSM require further investigation."}
{"id": "PMID:212547", "title": "Postsynaptic facilitatory effects of theophylline on amphibian neuromyal transmission.", "content": "This study concerns the effects of theophylline on nerve-muscle transmission of the frog; it was of particular interest to evaluate the facilitatory actions of theophylline at the postsynaptic sites. At concentrations of up to 5 mM, theophylline exerted negligible effects on the end-plate resting potential or on the passive membrane characteristics. The major effects of theophylline (0.5--5.0 mM) were exerted on the end-plate potentials (EPPs), miniature EPPs, acetylcholine (ACh) potentials, and on the end-plate current. The amplitude of these parameters was markedly increased; furthermore, the half-decay time of the EPP and, particularly, of the end-plate current were markedly affected. On the other hand, the time course of the ACh potentials was not significantly affected by theophylline. Spontaneous and evoked release of ACh were not affected by theophylline (0.5--5 mM). Altogether, these results indicate that, in amphibia, the neuromyal facilitation induced by theophylline is mainly due to its postsynaptic actions. Furthermore, some of these data as well as results of others indicate that these effects of theophylline are not due to its anticholinesterase properties. It is suggested that theophylline may act directly on the cholinergic receptor or ionic conductance modulator and that it may stabilize the ACh-receptor complex.", "contents": "Postsynaptic facilitatory effects of theophylline on amphibian neuromyal transmission. This study concerns the effects of theophylline on nerve-muscle transmission of the frog; it was of particular interest to evaluate the facilitatory actions of theophylline at the postsynaptic sites. At concentrations of up to 5 mM, theophylline exerted negligible effects on the end-plate resting potential or on the passive membrane characteristics. The major effects of theophylline (0.5--5.0 mM) were exerted on the end-plate potentials (EPPs), miniature EPPs, acetylcholine (ACh) potentials, and on the end-plate current. The amplitude of these parameters was markedly increased; furthermore, the half-decay time of the EPP and, particularly, of the end-plate current were markedly affected. On the other hand, the time course of the ACh potentials was not significantly affected by theophylline. Spontaneous and evoked release of ACh were not affected by theophylline (0.5--5 mM). Altogether, these results indicate that, in amphibia, the neuromyal facilitation induced by theophylline is mainly due to its postsynaptic actions. Furthermore, some of these data as well as results of others indicate that these effects of theophylline are not due to its anticholinesterase properties. It is suggested that theophylline may act directly on the cholinergic receptor or ionic conductance modulator and that it may stabilize the ACh-receptor complex."}
{"id": "PMID:212548", "title": "2,3-Dimercaptosuccinic acid: a new agent for the treatment of lead poisoning.", "content": "Using minimally lead-poisoned rats, we have measured urinary and fecal lead excretion in response to 2,3-dimercaptosuccinic acid (DMS) administered i.p. or p.o. and compared it to that induced by dimercaptopropanol (BAL) (i.p.), EDTA (i.p.), D-penicillamine (p.o. and i.p.) and the combination of BAL and EDTA (i.p.). At doses of 30 mg/kg, parenterally administered DMS was as effective as i.p. BAL and these two drugs were more effective than the other treatment groups. However, p.o. DMS was only 20% less effective and was as effective as i.p. EDTA and the combination of EDTA + BAL i.p. and significantly more effective than D-penicillamine p.o. or i.p. Unlike BAL, most lead excretion in response to DMS was via the urine, undoubtedly reflecting the greater water solubility of DMS. When mice were fed a diet containing both lead and DMS, the drug prevented the accumulation of porphyrins in erythrocytes. Studies with 210Pb indicate that this prophylactic effect is not due to an inhibition of lead absorption but rather to enhanced excretion of lead. The residual tissue distribution of 210 Pb administered simultaneously with DMS was not different form that of 210Pb alone. Since DMS is orally effective and its LD50 is 30 times greater than that of BAL, we expect this compound to be clinically useful in the treatment of lead poisoning.", "contents": "2,3-Dimercaptosuccinic acid: a new agent for the treatment of lead poisoning. Using minimally lead-poisoned rats, we have measured urinary and fecal lead excretion in response to 2,3-dimercaptosuccinic acid (DMS) administered i.p. or p.o. and compared it to that induced by dimercaptopropanol (BAL) (i.p.), EDTA (i.p.), D-penicillamine (p.o. and i.p.) and the combination of BAL and EDTA (i.p.). At doses of 30 mg/kg, parenterally administered DMS was as effective as i.p. BAL and these two drugs were more effective than the other treatment groups. However, p.o. DMS was only 20% less effective and was as effective as i.p. EDTA and the combination of EDTA + BAL i.p. and significantly more effective than D-penicillamine p.o. or i.p. Unlike BAL, most lead excretion in response to DMS was via the urine, undoubtedly reflecting the greater water solubility of DMS. When mice were fed a diet containing both lead and DMS, the drug prevented the accumulation of porphyrins in erythrocytes. Studies with 210Pb indicate that this prophylactic effect is not due to an inhibition of lead absorption but rather to enhanced excretion of lead. The residual tissue distribution of 210 Pb administered simultaneously with DMS was not different form that of 210Pb alone. Since DMS is orally effective and its LD50 is 30 times greater than that of BAL, we expect this compound to be clinically useful in the treatment of lead poisoning."}
{"id": "PMID:212549", "title": "Effects of adenosine triphosphate and prostaglandins on vascular adrenergic transmission.", "content": "The effects of prostaglandins (PGs) on the adrenergic neuroeffector transmission and their relationship to the action of ATP were investigated. This was in view of the putative negative feedback mediated by ATP or a related purine compound, and the reported stimulation of PG synthesis by adenine nucleotides. The central ear artery and saphenous vein of the rabbit were isolated and their contractile responses to adrenergic nerve stimulation monitored. These responses were markedly reduced by PGE1 and PGE2 and significantly augmented by indomethacin and aspirin, suggesting the occurrence of the PGE-mediated negative feedback. PGF2a facilitated the response of the vein but was without affect on the artery, while arachidonic acid was facilitatory on the former and inhibitory on the latter. Possibly a PGF2a-like substance is formed in the presence of arachidonic acid and, in the vein, masks the effect of any PGE. ATP depressed the arterial and venous contractile response to adrenergic nerve stimulation. This inhibition was not significantly affected by indomethacin or aspirin. It was enhanced in the artery and diminished in the vein by arachidonic acid, but only to the extent of algebraic sum of the effects of ATP and the acid. It seems possible that the purine- and PGE-mediated feedback mechanisms are independent and parallel pathways.", "contents": "Effects of adenosine triphosphate and prostaglandins on vascular adrenergic transmission. The effects of prostaglandins (PGs) on the adrenergic neuroeffector transmission and their relationship to the action of ATP were investigated. This was in view of the putative negative feedback mediated by ATP or a related purine compound, and the reported stimulation of PG synthesis by adenine nucleotides. The central ear artery and saphenous vein of the rabbit were isolated and their contractile responses to adrenergic nerve stimulation monitored. These responses were markedly reduced by PGE1 and PGE2 and significantly augmented by indomethacin and aspirin, suggesting the occurrence of the PGE-mediated negative feedback. PGF2a facilitated the response of the vein but was without affect on the artery, while arachidonic acid was facilitatory on the former and inhibitory on the latter. Possibly a PGF2a-like substance is formed in the presence of arachidonic acid and, in the vein, masks the effect of any PGE. ATP depressed the arterial and venous contractile response to adrenergic nerve stimulation. This inhibition was not significantly affected by indomethacin or aspirin. It was enhanced in the artery and diminished in the vein by arachidonic acid, but only to the extent of algebraic sum of the effects of ATP and the acid. It seems possible that the purine- and PGE-mediated feedback mechanisms are independent and parallel pathways."}
{"id": "PMID:212550", "title": "Modulation of transmission at an inhibitory synapse in the central nervous system of the leech.", "content": "The synaptic interactions among a group of cells in the leech C.N.S. that regulate the animal's heartbeat exhibit several remarkable features (Thompson & Stent, 1976 a, b, c). We have examined in detail the properties of the inhibitory synapse between two of these cells, the heart interneurone (HN cell) and the heart excitor motoneurone (HE cell). 1. Impulses in the presynaptic HN cell gave rise to monosynaptic i.p.s.p.s in the HE cell that were blocked by high concentrations of Mg and were reversed when the membrane potential of the post-synaptic motoneurone was hyperpolarized beyond--75 m V or when Cl was injected into the cell body. These i.p.s.p.s were chemically mediated, and involved an increase in chloride conductance. 2. In contrast to chemical synapses between sensory and motor cells in the leech C.N.S., little facilitation or depression of transmission occurred when the HN cell was stimulated at frequencies of 0.1--50 Hz. 3. Steady subthreshold depolarization of the presynaptic HN interneurone evoked a maintained hyperpolarization of the post-synaptic HE cell, indicating that currents injected into the HN cell body could spread to the terminals and cause continuous release of transmitter. 4. The size of the i.p.s.p. evoked in the HE motoneurone by an action potential in the HN interneurone varied with the resting membrane potential of the presynaptic cell. An impulse superimposed on a prolonged, subthreshold, depolarizing pulse produced a larger i.p.s.p.; conversely, prolonged hyperpolarization of the HN interneurone reduced the i.p.s.p. amplitude recorded in the HE cell. This effect was most obvious when the natural, rhythmical bursts of activity in the HN interneurone were interrupted by bathing the preparation in leech Ringer fluid containing elevated concentrations of Mg. Under these conditions a 10 mV depolarization of the HN cell increased the size of the i.p.s.p. in the HE cell approximately sixfold. Significant changes in i.p.s.p. amplitude occurred without any noticeable change in the amplitude and duration of the presynaptic action potential. With large presynaptic depolarizations, which produced the biggest i.p.s.p.s, there was some reduction in the amplitude and increase in the duration of the action potential. 5. Following a step depolarization of the presynaptic cell, the size of successive i.p.s.p.s increased with a time constant of about 1 sec. Upon repolarization the i.p.s.p.s decreased in amplitude to the original level. 6. stimulation of one HN cell also gives rise to an i.p.s.p. in its contralateral homologue (Thompson & Stent, 1976c). Trains of i.p.s.p.s produced in this way hyperpolarized at HN cell to such an extent that the size of the synaptic potential it evoked in an HE cell was reduced. 7. Thus, an HN interneurone inhibitis transmission between the contralateral HN and HE cells presynapitcally in addition to inhibiting directly the ipsilateral HE motoneurone.", "contents": "Modulation of transmission at an inhibitory synapse in the central nervous system of the leech. The synaptic interactions among a group of cells in the leech C.N.S. that regulate the animal's heartbeat exhibit several remarkable features (Thompson & Stent, 1976 a, b, c). We have examined in detail the properties of the inhibitory synapse between two of these cells, the heart interneurone (HN cell) and the heart excitor motoneurone (HE cell). 1. Impulses in the presynaptic HN cell gave rise to monosynaptic i.p.s.p.s in the HE cell that were blocked by high concentrations of Mg and were reversed when the membrane potential of the post-synaptic motoneurone was hyperpolarized beyond--75 m V or when Cl was injected into the cell body. These i.p.s.p.s were chemically mediated, and involved an increase in chloride conductance. 2. In contrast to chemical synapses between sensory and motor cells in the leech C.N.S., little facilitation or depression of transmission occurred when the HN cell was stimulated at frequencies of 0.1--50 Hz. 3. Steady subthreshold depolarization of the presynaptic HN interneurone evoked a maintained hyperpolarization of the post-synaptic HE cell, indicating that currents injected into the HN cell body could spread to the terminals and cause continuous release of transmitter. 4. The size of the i.p.s.p. evoked in the HE motoneurone by an action potential in the HN interneurone varied with the resting membrane potential of the presynaptic cell. An impulse superimposed on a prolonged, subthreshold, depolarizing pulse produced a larger i.p.s.p.; conversely, prolonged hyperpolarization of the HN interneurone reduced the i.p.s.p. amplitude recorded in the HE cell. This effect was most obvious when the natural, rhythmical bursts of activity in the HN interneurone were interrupted by bathing the preparation in leech Ringer fluid containing elevated concentrations of Mg. Under these conditions a 10 mV depolarization of the HN cell increased the size of the i.p.s.p. in the HE cell approximately sixfold. Significant changes in i.p.s.p. amplitude occurred without any noticeable change in the amplitude and duration of the presynaptic action potential. With large presynaptic depolarizations, which produced the biggest i.p.s.p.s, there was some reduction in the amplitude and increase in the duration of the action potential. 5. Following a step depolarization of the presynaptic cell, the size of successive i.p.s.p.s increased with a time constant of about 1 sec. Upon repolarization the i.p.s.p.s decreased in amplitude to the original level. 6. stimulation of one HN cell also gives rise to an i.p.s.p. in its contralateral homologue (Thompson & Stent, 1976c). Trains of i.p.s.p.s produced in this way hyperpolarized at HN cell to such an extent that the size of the synaptic potential it evoked in an HE cell was reduced. 7. Thus, an HN interneurone inhibitis transmission between the contralateral HN and HE cells presynapitcally in addition to inhibiting directly the ipsilateral HE motoneurone."}
{"id": "PMID:212551", "title": "Quantal analysis of transmitter release at an inhibitory synapse in the central nervous system of the leech.", "content": "The quantal nature of transmitter release has been analysed at central inhibitory synapses in the leech nervous system between an interneurone (HN) and a motoneurone (HE) that regulate the heartbeat. 1. Ganglia were bathed in leech Ringer fluid containing 20 mM-Mg and 1.8 mM-Ca and the membrane of the presynaptic HN interneurone was hyperpolarized by current injection. Under these conditions successive inhibitory potentials in the HE motoneurone, evoked by impulses in the HN interneurone, showed striking fluctuations in amplitude. 2. Assuming a Poisson distribution of the i.p.s.p.s and estimating the number of failures from the amplitude histograms of the observed responses, the mean size of the quantal unit was estimated as 0.25 +/- 0.015 mV (S.E. of mean, n = 26). When m, the mean number of quanta released per trial, was varied by changing the membrane potential of the presynaptic HN cell (Nicholls & Wallace, 1978), the experimentally observed amplitude distributions could be predicted by the Poisson theory. 3. An independent estimate of the unit size was obtained by noise analysis. A long subthreshold depolarizing pulse applied to the presynaptic HN interneurone evoked a sustained hyperpolarization of the HE motoneurone, apparently caused by an increase in the rate of on-going release of quanta by the HN cell terminals. From the mean change in membrane potential and the increase in variance, the size of the unit was calculated as 0.21 +/- 0.039 mV (S.E. of mean, n = 11). For ten pairs of cells an estimate of unit amplitude was made both from the Poisson analysis and the analysis of variance, again with good agreement. For these cells the estimated unit sizes were 0.24 +/- 0.023 mV (S.E. of mean, n = 10) from the failures and 0.21 +/- 0.043 m V (S.E. of mean, n = 10) from the noise. 4. A similar analysis was made of the inhibitory synaptic potentials evoked in one HN interneurone by stimulation of its contralateral homologue. Transmission again appeared to be qualtal; the mean unit amplitude from Poisson analysis was 0.31 +/- 0.022 mV (S.E. of mean, n = 19) and from the noise 0.29 +/- 0.027 mV (S.E. of mean, n = 3). 5. We conclude that transmitter is released from the terminals of the HN interneurone in quantal units that evoke miniature i.p.s.p.s of about 0.25 mV in the post-synaptic cells. Furthermore, modulation of transmission proudced by variation in the presynaptic resting potential and during presynaptic inhibition results from changes in the mean number of quanta released by each impulse.", "contents": "Quantal analysis of transmitter release at an inhibitory synapse in the central nervous system of the leech. The quantal nature of transmitter release has been analysed at central inhibitory synapses in the leech nervous system between an interneurone (HN) and a motoneurone (HE) that regulate the heartbeat. 1. Ganglia were bathed in leech Ringer fluid containing 20 mM-Mg and 1.8 mM-Ca and the membrane of the presynaptic HN interneurone was hyperpolarized by current injection. Under these conditions successive inhibitory potentials in the HE motoneurone, evoked by impulses in the HN interneurone, showed striking fluctuations in amplitude. 2. Assuming a Poisson distribution of the i.p.s.p.s and estimating the number of failures from the amplitude histograms of the observed responses, the mean size of the quantal unit was estimated as 0.25 +/- 0.015 mV (S.E. of mean, n = 26). When m, the mean number of quanta released per trial, was varied by changing the membrane potential of the presynaptic HN cell (Nicholls & Wallace, 1978), the experimentally observed amplitude distributions could be predicted by the Poisson theory. 3. An independent estimate of the unit size was obtained by noise analysis. A long subthreshold depolarizing pulse applied to the presynaptic HN interneurone evoked a sustained hyperpolarization of the HE motoneurone, apparently caused by an increase in the rate of on-going release of quanta by the HN cell terminals. From the mean change in membrane potential and the increase in variance, the size of the unit was calculated as 0.21 +/- 0.039 mV (S.E. of mean, n = 11). For ten pairs of cells an estimate of unit amplitude was made both from the Poisson analysis and the analysis of variance, again with good agreement. For these cells the estimated unit sizes were 0.24 +/- 0.023 mV (S.E. of mean, n = 10) from the failures and 0.21 +/- 0.043 m V (S.E. of mean, n = 10) from the noise. 4. A similar analysis was made of the inhibitory synaptic potentials evoked in one HN interneurone by stimulation of its contralateral homologue. Transmission again appeared to be qualtal; the mean unit amplitude from Poisson analysis was 0.31 +/- 0.022 mV (S.E. of mean, n = 19) and from the noise 0.29 +/- 0.027 mV (S.E. of mean, n = 3). 5. We conclude that transmitter is released from the terminals of the HN interneurone in quantal units that evoke miniature i.p.s.p.s of about 0.25 mV in the post-synaptic cells. Furthermore, modulation of transmission proudced by variation in the presynaptic resting potential and during presynaptic inhibition results from changes in the mean number of quanta released by each impulse."}
{"id": "PMID:212553", "title": "An alpha-adrenergic receptor mechanism controlling potassium permeability in the rat lacrimal gland acinar cell.", "content": "1. Rat lacrimal gland slices, incubated in a balanced, buffered salt solution, were found to be physiologically stable for up to 2 hr with respect to O2 consumption, extracellular space, and water and ion content. 2. The release of 86Rb serves as a good substitute for 42K in monitoring the movement of K through the cell membrane. 3. Adrenaline appears to increase membrane permeability to K as evidenced by an increase in the rate of 86Rb efflux. 4. This response to adrenaline was blocked by phentolamine but not by propranolol and was mimicked by phenylephrine but not by isoprenaline. 5. The magnitude of the 86Rb release indicates that it is being released, at least in part, from the lacrimal gland acinar cell. 6. It is concluded that the lacrimal gland acinar cell has an alpha-adrenergic receptor, activation of which leads to an increase in membrane permeability to K.", "contents": "An alpha-adrenergic receptor mechanism controlling potassium permeability in the rat lacrimal gland acinar cell. 1. Rat lacrimal gland slices, incubated in a balanced, buffered salt solution, were found to be physiologically stable for up to 2 hr with respect to O2 consumption, extracellular space, and water and ion content. 2. The release of 86Rb serves as a good substitute for 42K in monitoring the movement of K through the cell membrane. 3. Adrenaline appears to increase membrane permeability to K as evidenced by an increase in the rate of 86Rb efflux. 4. This response to adrenaline was blocked by phentolamine but not by propranolol and was mimicked by phenylephrine but not by isoprenaline. 5. The magnitude of the 86Rb release indicates that it is being released, at least in part, from the lacrimal gland acinar cell. 6. It is concluded that the lacrimal gland acinar cell has an alpha-adrenergic receptor, activation of which leads to an increase in membrane permeability to K."}
{"id": "PMID:212554", "title": "The role of calcium in the receptor mediated control of potassium permeability in the rat lacrimal gland.", "content": "1. In the presence of extracellular Ca, adrenaline stimulated a large increase in the rate of K (86Rb) release from rat lacrimal slices, followed by a lower, more sustained rate. 2. In the absence of extracellular Ca, adrenaline elicited only a transient release of 86Rb. 3. The artificial introduction of Ca into the cytosol by the ionophore A-23187 could also initiate the release of 86Rb. 4. In a zero-Ca medium, if either adrenaline or carbachol produced a transient release of 86Rb, the tissue could not respond to the other agonist with a transient release unless Ca was momentarily reintroduced to the medium. 5. If Ca was present in a limiting concentration, the Ca-dependent rate of 86Rb release elicited from a lacrimal slice exposed simultaneously to carbachol and adrenaline was not significantly different from the release seen with carbachol alone. 6. It is concluded that the agonist-induced release of K from the lacrimal gland consists of both a Ca-independent phase which is initiated by the release of a limited pool of Ca, and a Ca-dependent phase which is mediated by the influx of extracellular Ca. 7. It is also concluded that both alpha-adrenergic and muscarinic receptor occupation activate a common, post-receptor mechanism which may be responsible for both phases of K release.", "contents": "The role of calcium in the receptor mediated control of potassium permeability in the rat lacrimal gland. 1. In the presence of extracellular Ca, adrenaline stimulated a large increase in the rate of K (86Rb) release from rat lacrimal slices, followed by a lower, more sustained rate. 2. In the absence of extracellular Ca, adrenaline elicited only a transient release of 86Rb. 3. The artificial introduction of Ca into the cytosol by the ionophore A-23187 could also initiate the release of 86Rb. 4. In a zero-Ca medium, if either adrenaline or carbachol produced a transient release of 86Rb, the tissue could not respond to the other agonist with a transient release unless Ca was momentarily reintroduced to the medium. 5. If Ca was present in a limiting concentration, the Ca-dependent rate of 86Rb release elicited from a lacrimal slice exposed simultaneously to carbachol and adrenaline was not significantly different from the release seen with carbachol alone. 6. It is concluded that the agonist-induced release of K from the lacrimal gland consists of both a Ca-independent phase which is initiated by the release of a limited pool of Ca, and a Ca-dependent phase which is mediated by the influx of extracellular Ca. 7. It is also concluded that both alpha-adrenergic and muscarinic receptor occupation activate a common, post-receptor mechanism which may be responsible for both phases of K release."}
{"id": "PMID:212555", "title": "Role of calcium in the fade of the potassium release response in the rat parotid gland.", "content": "1. The 86Rb release response in the parotid due to alpha-adrenergic (epinephrine), muscarinic (carbachol) or peptide (Substance P) receptor activation exhibited 'fade': a return of efflux to control levels despite the continuing presence of agonist. 2. The time course of fade of the response to all three agonists was independent of the concentration of the agonist. 3. After fade was fully developed to one agonist, the response to an agonist acting on a different receptor was either absent or greatly diminished. 4. Removal of carbachol from muscarinic receptors with atropine 10 min prior to Substance P partially restored the ability of Substance P to produce a response. 5. Fade of the response with all three agonists was greatly retarded by the omission of Ca. 6. release of alpha-amylase did not appear to fade following exposure to carbachol or Substance P. 7. It is concluded that the K+ release response may be inactivated with time due to diminution in responsiveness of the K+ channel to an increase in internal Ca2+.", "contents": "Role of calcium in the fade of the potassium release response in the rat parotid gland. 1. The 86Rb release response in the parotid due to alpha-adrenergic (epinephrine), muscarinic (carbachol) or peptide (Substance P) receptor activation exhibited 'fade': a return of efflux to control levels despite the continuing presence of agonist. 2. The time course of fade of the response to all three agonists was independent of the concentration of the agonist. 3. After fade was fully developed to one agonist, the response to an agonist acting on a different receptor was either absent or greatly diminished. 4. Removal of carbachol from muscarinic receptors with atropine 10 min prior to Substance P partially restored the ability of Substance P to produce a response. 5. Fade of the response with all three agonists was greatly retarded by the omission of Ca. 6. release of alpha-amylase did not appear to fade following exposure to carbachol or Substance P. 7. It is concluded that the K+ release response may be inactivated with time due to diminution in responsiveness of the K+ channel to an increase in internal Ca2+."}
{"id": "PMID:212556", "title": "A voltage-clamp study of the permeability change induced by quanta of transmitter at the mouse end-plate.", "content": "1. Miniature end-plate currents (m.e.p.c.s) were recorded from mouse diaphragm using a point voltage-clamp. The relation between m.e.p.c. amplitude and membrane potential was determined in bathing solutions of varied composition. 2. In solution containing normal sodium the relation between m.e.p.c. height and membrane potential (Im.e.p.c./Vm relation) was always linear, at least in the range +30 to -100 mV; the reversal potential (Vr) at which Im.e.p.c. was zero was close to 0. The slope of the Im.e.p.c./Vm line varied little between junctions (coefficient of variation about 20%) and was about 50 nS, or 1nA per 20 mV. The Im.e.p.c./Vm relation was not altered by withdrawal of Ca2+, addition of ethanol, or substitution of NO-3 or SO2-(4) for Cl-. 3. Alteration of K+ concentration in the bathing medium, in the range 10 to 1 mM, had no apparent effect on the Im.e.p.c./Vm relation. 4. Reduction of Na+ concentration, with isosmotic substitution of sucrose, caused rapid alteration of the Im.e.p.c./Vm relation, which became rectifying, with a slope at negative Vm less than at positive Vm. Vr was shifted in the negative direction. Quantitatively these changes were close to those predicted by the Goldman-Hodgkin-Katz formulation for permeation of monovalent ions through a membrane with constant field. 5. In solution with low Na+ (2 mM) and partial substitution of K+ for Na+, the Im.e.p.c./Vm relation was indistinguishable from that in solutions with Na\" as the predominant extracellular cation. With complete substitution of K+ for Na+ the Im.e.p.c./Vm relation was a little less steep (at negative Vm) than in Na+ solution and Vr was shifted slightly in the negative direction. 6. With substitution of NH+4 for Na+, the Im.e.p.c./Vm relation was little changed (about 10% steeper at negative Vm). With substitution of Li+ for Na+, the Im.e.p.c./Vm relation remained linear, but was made less steep, at positive as well as negative Vm, and Vr was shifted slightly in the positive direction. 7. These results indicate that the permeability change associated with generation of the m.e.p.c. (i.e., evoked by a quantum of transmitter) corresponds to the opening of a single species of membrane channel that allows the free movement of K+, Na+, NH+4, AND Li+ ions along their electrochemical gradients. The channel discriminates little between these ions. The apparent order of permeability is Li+ greater than NH+4 greater than Na+ greater than or equal to K+. The apparent permeability per channel corresponds to that expected for channels of about 6.4 A diameter, 100 A length, and ionic mobility the same as in dilute solution.", "contents": "A voltage-clamp study of the permeability change induced by quanta of transmitter at the mouse end-plate. 1. Miniature end-plate currents (m.e.p.c.s) were recorded from mouse diaphragm using a point voltage-clamp. The relation between m.e.p.c. amplitude and membrane potential was determined in bathing solutions of varied composition. 2. In solution containing normal sodium the relation between m.e.p.c. height and membrane potential (Im.e.p.c./Vm relation) was always linear, at least in the range +30 to -100 mV; the reversal potential (Vr) at which Im.e.p.c. was zero was close to 0. The slope of the Im.e.p.c./Vm line varied little between junctions (coefficient of variation about 20%) and was about 50 nS, or 1nA per 20 mV. The Im.e.p.c./Vm relation was not altered by withdrawal of Ca2+, addition of ethanol, or substitution of NO-3 or SO2-(4) for Cl-. 3. Alteration of K+ concentration in the bathing medium, in the range 10 to 1 mM, had no apparent effect on the Im.e.p.c./Vm relation. 4. Reduction of Na+ concentration, with isosmotic substitution of sucrose, caused rapid alteration of the Im.e.p.c./Vm relation, which became rectifying, with a slope at negative Vm less than at positive Vm. Vr was shifted in the negative direction. Quantitatively these changes were close to those predicted by the Goldman-Hodgkin-Katz formulation for permeation of monovalent ions through a membrane with constant field. 5. In solution with low Na+ (2 mM) and partial substitution of K+ for Na+, the Im.e.p.c./Vm relation was indistinguishable from that in solutions with Na\" as the predominant extracellular cation. With complete substitution of K+ for Na+ the Im.e.p.c./Vm relation was a little less steep (at negative Vm) than in Na+ solution and Vr was shifted slightly in the negative direction. 6. With substitution of NH+4 for Na+, the Im.e.p.c./Vm relation was little changed (about 10% steeper at negative Vm). With substitution of Li+ for Na+, the Im.e.p.c./Vm relation remained linear, but was made less steep, at positive as well as negative Vm, and Vr was shifted slightly in the positive direction. 7. These results indicate that the permeability change associated with generation of the m.e.p.c. (i.e., evoked by a quantum of transmitter) corresponds to the opening of a single species of membrane channel that allows the free movement of K+, Na+, NH+4, AND Li+ ions along their electrochemical gradients. The channel discriminates little between these ions. The apparent order of permeability is Li+ greater than NH+4 greater than Na+ greater than or equal to K+. The apparent permeability per channel corresponds to that expected for channels of about 6.4 A diameter, 100 A length, and ionic mobility the same as in dilute solution."}
{"id": "PMID:212557", "title": "Multiple innervation of normal and re-innervated parasympathetic neurones in the frog cardiac ganglion.", "content": "1. Multiple innervation of parasympathetic neurones was examined in normal and re-innervated frog cardiac ganglia. The number of synaptic inputs impinging upon individual ganglion cells was determined by recording intracellularly and stimulating the vagosympathetic nerves. 2. In unoperated cardiac ganglia most neurones (93%) received a large, suprathreshold synaptic input. Some ganglion cells received additional, small synaptic inputs. Roughly equal numbers of cells encountered were singly and doubly innervated, and only 8% received more than two inputs. 3. Re-innervation of cardiac ganglion cells began three weeks after bilateral crush of the vagosympathetic nerves. By 7 weeks more than 90% of the ganglion cells were re-innervated. At this stage the pattern of multiple innervation was significantly different than normal: doubly innervated neurones outnumbered singly innervated ones, and 31% of the cells encountered received more than two inputs. This pattern was stable for at least a year. 4. These results indicate that polyneuronal innervation of cardiac ganglion cells is more widespread after re-innervation than it is normally and, furthermore, that synapse elimination does not occur during re-innervation of these cells.", "contents": "Multiple innervation of normal and re-innervated parasympathetic neurones in the frog cardiac ganglion. 1. Multiple innervation of parasympathetic neurones was examined in normal and re-innervated frog cardiac ganglia. The number of synaptic inputs impinging upon individual ganglion cells was determined by recording intracellularly and stimulating the vagosympathetic nerves. 2. In unoperated cardiac ganglia most neurones (93%) received a large, suprathreshold synaptic input. Some ganglion cells received additional, small synaptic inputs. Roughly equal numbers of cells encountered were singly and doubly innervated, and only 8% received more than two inputs. 3. Re-innervation of cardiac ganglion cells began three weeks after bilateral crush of the vagosympathetic nerves. By 7 weeks more than 90% of the ganglion cells were re-innervated. At this stage the pattern of multiple innervation was significantly different than normal: doubly innervated neurones outnumbered singly innervated ones, and 31% of the cells encountered received more than two inputs. This pattern was stable for at least a year. 4. These results indicate that polyneuronal innervation of cardiac ganglion cells is more widespread after re-innervation than it is normally and, furthermore, that synapse elimination does not occur during re-innervation of these cells."}
{"id": "PMID:212558", "title": "A follow-up of self-poisoned patients.", "content": "Over half the patients who were admitted to hospital after self-poisoning had seen their general practitioner in the previous month, and in half of those discharged from hospital no definite after-care arrangements were made. Opportunities for prevention of occurrences are being missed. Thorough follow-up of 135 such patients identified many non-medical problems, and over 80 per cent were helped by appropriate referral. Although only five of these patients made a further attempt during the period of review, the method of selection of patients does not allow definite conclusions to be made.", "contents": "A follow-up of self-poisoned patients. Over half the patients who were admitted to hospital after self-poisoning had seen their general practitioner in the previous month, and in half of those discharged from hospital no definite after-care arrangements were made. Opportunities for prevention of occurrences are being missed. Thorough follow-up of 135 such patients identified many non-medical problems, and over 80 per cent were helped by appropriate referral. Although only five of these patients made a further attempt during the period of review, the method of selection of patients does not allow definite conclusions to be made."}
{"id": "PMID:212561", "title": "[Virus diarrhea in calves in South Africa].", "content": "The importance of diarrhoea in calves is briefly discussed. The role of viruses as primary invaders of the intestinal epithelium is stressed. The pathogenesis and problems encountered in diagnosing virus associated diarrhoea as well as the morphology of rota and coranavirus are discussed. Possible methods of prevention and treatment are briefly mentioned.", "contents": "[Virus diarrhea in calves in South Africa]. The importance of diarrhoea in calves is briefly discussed. The role of viruses as primary invaders of the intestinal epithelium is stressed. The pathogenesis and problems encountered in diagnosing virus associated diarrhoea as well as the morphology of rota and coranavirus are discussed. Possible methods of prevention and treatment are briefly mentioned."}
{"id": "PMID:212565", "title": "Cytogenetic diagnosis of cancer: abnormalities of chromosomes and polyploid levels in the bone marrow of patients with small cell anaplastic carcinoma of the lung.", "content": "The chromosomes of metastatic cells and polyploid levels in the bone marrow of 26 patients with small cell anaplastic carcinoma were studied by direct bone marrow preparation and trypsin-Giemsa banding. Eighteen of these patients had received no tumor therapy and 8 had had chemotherapy and/or radiation therapy; 18 patients, including 5 who had received therapy, had karyotypic abnormalities with or without elevation of the polyploid level. Modal numbers and chromosome abnormalities were highly variable in treated and untreated patients. Modes ranged from hypodiploid to polyploid, but polyploid modes were the most frequently observed abnormal modes. Polyploid modes were not seen, however, in post-therapy patients with the exception of one who had received radiation therapy to the mediastinum for only 4 days prior to withdrawal of the specimen for chromosome analysis. Ten patients had elevated polyploid levels that ranged from 4.24 to 44.8% and always occurred in conjunction with karyotypic abnormalities. Both aneusomy (abnormal number) of normal chromosomes and structural aberrations (markers) occurred frequently. Some markers were consistent within an individual, but other variable aberrations were also typically present. Very few markers were common to 2 or more patients. The no. 1 chromosome participated in marker formation in 14 of the 18 patients with karyotypic abnormalities. Of the 26 patients, 5 were negative for metastasis to the marrow by pathologic examination but positive by cytogenetic diagnosis, whereas none were positive by pathologic examination and negative by cytogenetic diagnosis; this demonstrated that cytogenetics may be used as a rapid adjunct diagnostic procedure for the detection of metastasis in the marrow.", "contents": "Cytogenetic diagnosis of cancer: abnormalities of chromosomes and polyploid levels in the bone marrow of patients with small cell anaplastic carcinoma of the lung. The chromosomes of metastatic cells and polyploid levels in the bone marrow of 26 patients with small cell anaplastic carcinoma were studied by direct bone marrow preparation and trypsin-Giemsa banding. Eighteen of these patients had received no tumor therapy and 8 had had chemotherapy and/or radiation therapy; 18 patients, including 5 who had received therapy, had karyotypic abnormalities with or without elevation of the polyploid level. Modal numbers and chromosome abnormalities were highly variable in treated and untreated patients. Modes ranged from hypodiploid to polyploid, but polyploid modes were the most frequently observed abnormal modes. Polyploid modes were not seen, however, in post-therapy patients with the exception of one who had received radiation therapy to the mediastinum for only 4 days prior to withdrawal of the specimen for chromosome analysis. Ten patients had elevated polyploid levels that ranged from 4.24 to 44.8% and always occurred in conjunction with karyotypic abnormalities. Both aneusomy (abnormal number) of normal chromosomes and structural aberrations (markers) occurred frequently. Some markers were consistent within an individual, but other variable aberrations were also typically present. Very few markers were common to 2 or more patients. The no. 1 chromosome participated in marker formation in 14 of the 18 patients with karyotypic abnormalities. Of the 26 patients, 5 were negative for metastasis to the marrow by pathologic examination but positive by cytogenetic diagnosis, whereas none were positive by pathologic examination and negative by cytogenetic diagnosis; this demonstrated that cytogenetics may be used as a rapid adjunct diagnostic procedure for the detection of metastasis in the marrow."}
{"id": "PMID:212566", "title": "Nucleases and adenosine 3',5'-cyclic monophosphate phosphodiesterase activities in murine sarcoma virus (Moloney)-infected mice.", "content": "To provide information on the role of nucleases in oncogenic virus infection, the activities of 3'-nucleotide phosphodiesterase (3'-NPDase), 5'-nucleotide phosphodiesterase (5'-NPDase), acid deoxyribonuclease (DNase II), and 3',5'-cyclic AMP phosphodiesterase (cAMPDase) in spleen extracts of murine sarcoma virus-infected C57BL/6 inbred mice were studied. At the peak of tumor growth and of the cell-mediated cytotoxic response (CMC) against tumor-associated antigens, 3'-NPDase, 5'-NPDase, and DNase II all showed depressed activities in the spleen, whereas the activity of cAMPDase in the spleen increased at the peak of CMC and remained elevated thereafter. Serum enzyme activities of the infected mice were also determined, and only 3'-NPD-ase in serum correlated well with CMC. Inasmuch as the correlation of the tumor growth with CMC was established in this system, further study on tumors with variance between CMC and growth is necessary to determine if serum 3'-NPDase is a useful biochemical marker for CMC in vivo.", "contents": "Nucleases and adenosine 3',5'-cyclic monophosphate phosphodiesterase activities in murine sarcoma virus (Moloney)-infected mice. To provide information on the role of nucleases in oncogenic virus infection, the activities of 3'-nucleotide phosphodiesterase (3'-NPDase), 5'-nucleotide phosphodiesterase (5'-NPDase), acid deoxyribonuclease (DNase II), and 3',5'-cyclic AMP phosphodiesterase (cAMPDase) in spleen extracts of murine sarcoma virus-infected C57BL/6 inbred mice were studied. At the peak of tumor growth and of the cell-mediated cytotoxic response (CMC) against tumor-associated antigens, 3'-NPDase, 5'-NPDase, and DNase II all showed depressed activities in the spleen, whereas the activity of cAMPDase in the spleen increased at the peak of CMC and remained elevated thereafter. Serum enzyme activities of the infected mice were also determined, and only 3'-NPD-ase in serum correlated well with CMC. Inasmuch as the correlation of the tumor growth with CMC was established in this system, further study on tumors with variance between CMC and growth is necessary to determine if serum 3'-NPDase is a useful biochemical marker for CMC in vivo."}
{"id": "PMID:212567", "title": "Natural transmission of gibbon leukemia virus.", "content": "Gibbon leukemia virus can infect prenatal gibbons through in utero infection or postnatal gibbons through contact transmission. The transmission of infectious virus was from viremic gibbons and not from uninfected or antibody-positive animals. The two modes of transmission could be distinguished by the amount of proviral DNA integrated into the muscle tissue of viremic gibbons. Muscle of gibbons infected postnatally had little or no proviral DNA, whereas gibbons infected prenatally had a large quantity of proviral DNA.", "contents": "Natural transmission of gibbon leukemia virus. Gibbon leukemia virus can infect prenatal gibbons through in utero infection or postnatal gibbons through contact transmission. The transmission of infectious virus was from viremic gibbons and not from uninfected or antibody-positive animals. The two modes of transmission could be distinguished by the amount of proviral DNA integrated into the muscle tissue of viremic gibbons. Muscle of gibbons infected postnatally had little or no proviral DNA, whereas gibbons infected prenatally had a large quantity of proviral DNA."}
{"id": "PMID:212568", "title": "Genetic analyses of differences in incidence of mammary tumors and reticulum cell neoplasms with the use of recombinant inbred lines of mice.", "content": "The influence of genes, in addition to genes in the H-2 complex, that effect the genesis of mammary tumors was studied. The recombinant inbred (RI) CXB lines were chosen for this investigation, because they are well suited for the study of the genetics of a trait for which the genotype affects probability of phenotype expression and which therefore is measured as incidence. Females of seven RI lines (CXBD, CXBE, CXBG, CXBH, CXBI, CXBJ, and CXBK) and their progenitor strains C57BL/6By (B6) and BALB/cBy (BALB/c) were given ip injections of MuMTV at 3 months of age and were force bred. They were observed for mammary tumors. The B6 strain was least susceptible, and mammary tumors appeared late in life. The BALB/c strain was most susceptible, and the tumors appeared early in life. The course of tumor development in the RI lines fell between these extremes. The RI strain distribution pattern of mammary tumor incidence indicated that at least one and probably several loci in addition to those at H-2 determined the difference between the BALB/c and B6 strains. Effects of the other gene(s) appeared to be even more important than those of H-2. The locations of those loci were not made clear by this study. The spontaneous incidence of reticulum cell neoplasms was also recorded. The most frequently formed neoplasm of the reticular system was a Hodgkin's-like lesion. The data suggested an influence of the H-2 complex.", "contents": "Genetic analyses of differences in incidence of mammary tumors and reticulum cell neoplasms with the use of recombinant inbred lines of mice. The influence of genes, in addition to genes in the H-2 complex, that effect the genesis of mammary tumors was studied. The recombinant inbred (RI) CXB lines were chosen for this investigation, because they are well suited for the study of the genetics of a trait for which the genotype affects probability of phenotype expression and which therefore is measured as incidence. Females of seven RI lines (CXBD, CXBE, CXBG, CXBH, CXBI, CXBJ, and CXBK) and their progenitor strains C57BL/6By (B6) and BALB/cBy (BALB/c) were given ip injections of MuMTV at 3 months of age and were force bred. They were observed for mammary tumors. The B6 strain was least susceptible, and mammary tumors appeared late in life. The BALB/c strain was most susceptible, and the tumors appeared early in life. The course of tumor development in the RI lines fell between these extremes. The RI strain distribution pattern of mammary tumor incidence indicated that at least one and probably several loci in addition to those at H-2 determined the difference between the BALB/c and B6 strains. Effects of the other gene(s) appeared to be even more important than those of H-2. The locations of those loci were not made clear by this study. The spontaneous incidence of reticulum cell neoplasms was also recorded. The most frequently formed neoplasm of the reticular system was a Hodgkin's-like lesion. The data suggested an influence of the H-2 complex."}
{"id": "PMID:212569", "title": "Antibody-dependent lysis of tumor cells in vivo. II. Elimination of chromium-51 as a measurement of cytolysis.", "content": "The effect of antibody on tumor cells was studied in vivo by measurement of the rate of elimination of 51Cr in A/J mice inoculated with labeled Ehrlich tumor cells. Mice receiving ip injections of tumor cells and normal serum eliminated 51Cr rapidly during the first 24 hours and at a much slower rate thereafter. This biphasic pattern of elimination was due to the fact that 51Cr predominantly labels small (less than 13,000 mol wt) intracellular molecules, which the mouse rapidly eliminates, whereas larger labeled molecules are eliminated slowly. Antibody to tumor cells significantly accelerated the elimination of 51Cr at concentrations that regularly suppressed tumor growth. Antibody also induced a faster elimination rate in mice treated with cobra venom factor but not in mice treated with silica or inoculated sc with the tumor cells. Unlabeled tumor cells inhibited antibody-induced 51Cr clearance in normal mice but not in proteose peptone-treated mice. These results suggested that peritoneal cells are required in the induction of antibody-dependent cytolysis in vivo. In addition, actively or passively alloimmunized mice exhibited a similar accelerated 51Cr elimination rate when inoculated with the appropriate labeled target cells.", "contents": "Antibody-dependent lysis of tumor cells in vivo. II. Elimination of chromium-51 as a measurement of cytolysis. The effect of antibody on tumor cells was studied in vivo by measurement of the rate of elimination of 51Cr in A/J mice inoculated with labeled Ehrlich tumor cells. Mice receiving ip injections of tumor cells and normal serum eliminated 51Cr rapidly during the first 24 hours and at a much slower rate thereafter. This biphasic pattern of elimination was due to the fact that 51Cr predominantly labels small (less than 13,000 mol wt) intracellular molecules, which the mouse rapidly eliminates, whereas larger labeled molecules are eliminated slowly. Antibody to tumor cells significantly accelerated the elimination of 51Cr at concentrations that regularly suppressed tumor growth. Antibody also induced a faster elimination rate in mice treated with cobra venom factor but not in mice treated with silica or inoculated sc with the tumor cells. Unlabeled tumor cells inhibited antibody-induced 51Cr clearance in normal mice but not in proteose peptone-treated mice. These results suggested that peritoneal cells are required in the induction of antibody-dependent cytolysis in vivo. In addition, actively or passively alloimmunized mice exhibited a similar accelerated 51Cr elimination rate when inoculated with the appropriate labeled target cells."}
{"id": "PMID:212570", "title": "Particle-enhanced membrane uptake of a polynuclear aromatic hydrocarbon: a possible role in cocarcinogenesis.", "content": "One possible mechanism by which cocarcinogenesis occurs was investigated. The effect of a particulate, silica, upon the rate of membrane uptake of a polynuclear aromatic hydrocarbon, benz[a]anthracene (BA), was studied. The fluorescence emission spectrum and quantum yield of BA, when adsorbed to silica, underwent spectral shifts upon addition of phospholipid vesicles. These spectral changes appeared to result from the transfer of BA from the silica surface into the lipid bilayer. We used these spectral changes to measure the rates of membrane uptake of BA from the silica-adsorbed state and from the crystalline and microcrystalline states of BA. Our studies demonstrated that adsorption of BA to silica resulted in an increased rate of uptake of BA into dipalmitoyl-L-alpha-phosphatidylcholine vesicles compared to the uptake rate into these vesicles from crystalling states. Such particle-enhanced membrane uptake of chemical carcinogens may be of importance in explaining the enhanced carcinogenicity of the polynuclear aromatic hydrocarbons in the presence of particulate matter.", "contents": "Particle-enhanced membrane uptake of a polynuclear aromatic hydrocarbon: a possible role in cocarcinogenesis. One possible mechanism by which cocarcinogenesis occurs was investigated. The effect of a particulate, silica, upon the rate of membrane uptake of a polynuclear aromatic hydrocarbon, benz[a]anthracene (BA), was studied. The fluorescence emission spectrum and quantum yield of BA, when adsorbed to silica, underwent spectral shifts upon addition of phospholipid vesicles. These spectral changes appeared to result from the transfer of BA from the silica surface into the lipid bilayer. We used these spectral changes to measure the rates of membrane uptake of BA from the silica-adsorbed state and from the crystalline and microcrystalline states of BA. Our studies demonstrated that adsorption of BA to silica resulted in an increased rate of uptake of BA into dipalmitoyl-L-alpha-phosphatidylcholine vesicles compared to the uptake rate into these vesicles from crystalling states. Such particle-enhanced membrane uptake of chemical carcinogens may be of importance in explaining the enhanced carcinogenicity of the polynuclear aromatic hydrocarbons in the presence of particulate matter."}
{"id": "PMID:212571", "title": "Cytogenetic studies of a simian virus 40 temperature-sensitive mutant-transformed Chinese hamster cell clone at the permissive and nonpermissive temperature.", "content": "A clone of Chinese hamster embryo cells transformed by tsA58, the temperature-sensitive mutant of simian virus 40, was analyzed for chromosome abnormalities at the permissive temperature (37 degrees C) and nonpermissive temperature (40.5 degrees C). Trypsin-Giemsa-banded metaphases were analyzed 1 week after the temperature shift. The metaphases from cells at both temperatures were pseudodiploid, with numerous chromosome changes primarily affecting chromosomes no. 1 and 2. Other chromosomes (no. 6, 11, and the X) were also frequently involved. A marker chromosome, LM, was present in 35% of the cells at 40.5 degrees C.", "contents": "Cytogenetic studies of a simian virus 40 temperature-sensitive mutant-transformed Chinese hamster cell clone at the permissive and nonpermissive temperature. A clone of Chinese hamster embryo cells transformed by tsA58, the temperature-sensitive mutant of simian virus 40, was analyzed for chromosome abnormalities at the permissive temperature (37 degrees C) and nonpermissive temperature (40.5 degrees C). Trypsin-Giemsa-banded metaphases were analyzed 1 week after the temperature shift. The metaphases from cells at both temperatures were pseudodiploid, with numerous chromosome changes primarily affecting chromosomes no. 1 and 2. Other chromosomes (no. 6, 11, and the X) were also frequently involved. A marker chromosome, LM, was present in 35% of the cells at 40.5 degrees C."}
{"id": "PMID:212572", "title": "Isolation of two human tumor epithelial cell lines from solid breast carcinomas.", "content": "Most of the available human breast tumor cell lines have been derived from pleural effusions. The two cell lines herein described, BT-474 and BT-483, were derived from solid, invasive ductal breast carcinomas. Both are epithelial and neoplastic as judged by their general morphology, their fine structure, and their ability to produce growing nodules in nude mice and colonies in soft agar and methocel. BT-474 and BT-483 are human as expressed by chromosome morphology and aneuploid with a modal number of 55 and 72 chromosomes, respectively. Trypsin-Giemsa banding did not reveal the presence of obvious HeLa markers, and the glucose 6-phosphate dehydrogenase electrophoretic migration pattern was of the B-type. Furthermore, the migration of lactic dehydrogenase, malic dehydrogenase, and 6-phosphogluconate dehydrogenase isoenzymes was consistent with a human pattern and different from that of the mouse, rat, or hamster. Quarterly tests to detect the presence of aerobic and anaerobic mycoplasmas were repeatedly negative. A culture medium containing insulin, increased amounts of amino acids, vitamins, and glucose facilitated the isolation of the tumor cells. Cell replication was maintained with 10% fetal calf serum absorbed with activated charcoal and dextran. No production of alpha-lactalbumin was detected by radioimmunoassays, but high levels of progesterone receptors were found in both cell lines.", "contents": "Isolation of two human tumor epithelial cell lines from solid breast carcinomas. Most of the available human breast tumor cell lines have been derived from pleural effusions. The two cell lines herein described, BT-474 and BT-483, were derived from solid, invasive ductal breast carcinomas. Both are epithelial and neoplastic as judged by their general morphology, their fine structure, and their ability to produce growing nodules in nude mice and colonies in soft agar and methocel. BT-474 and BT-483 are human as expressed by chromosome morphology and aneuploid with a modal number of 55 and 72 chromosomes, respectively. Trypsin-Giemsa banding did not reveal the presence of obvious HeLa markers, and the glucose 6-phosphate dehydrogenase electrophoretic migration pattern was of the B-type. Furthermore, the migration of lactic dehydrogenase, malic dehydrogenase, and 6-phosphogluconate dehydrogenase isoenzymes was consistent with a human pattern and different from that of the mouse, rat, or hamster. Quarterly tests to detect the presence of aerobic and anaerobic mycoplasmas were repeatedly negative. A culture medium containing insulin, increased amounts of amino acids, vitamins, and glucose facilitated the isolation of the tumor cells. Cell replication was maintained with 10% fetal calf serum absorbed with activated charcoal and dextran. No production of alpha-lactalbumin was detected by radioimmunoassays, but high levels of progesterone receptors were found in both cell lines."}
{"id": "PMID:212573", "title": "Colony formation by simian virus 40-transformed human parapharyngeal cells cultured in semisolid agar.", "content": "A simian virus 40 (SV40)-transformed line of human parapharyngeal cells (SV-TGo) was cultured in semisolid agar to determine its ability to grow in the absence of an anchoring substratum and to evaluate any phenotypic changes that might have resulted during the isolation of sublines specifically selected for anchorage independence. After 2--3 weeks and 14--15 population doublings in culture, SV-TGo plated with over 1,000% higher efficiency than negative controls (F2408 cells). Sublines, 0.3--2.0 mm in diameter, were isolated and transferred to Leighton tubes in which they underwent an additional 0--7 divisions before senescence after 39--44 total population doublings. Subline phenotype was identical to the original parental phenotype, including epithelioid morphology, organized pattern of growth, extreme sensitivity to density-dependent inhibition of growth, and continuous production of infectious SV40 as detected by the combined tests of cocultivation and direct isolation. Limited division potential was within the range observed for the parental line. The ability to grow in agar without identifiable phenotypic changes was therefore confirmed for this line of SV40-transformed human epithelioid cells.", "contents": "Colony formation by simian virus 40-transformed human parapharyngeal cells cultured in semisolid agar. A simian virus 40 (SV40)-transformed line of human parapharyngeal cells (SV-TGo) was cultured in semisolid agar to determine its ability to grow in the absence of an anchoring substratum and to evaluate any phenotypic changes that might have resulted during the isolation of sublines specifically selected for anchorage independence. After 2--3 weeks and 14--15 population doublings in culture, SV-TGo plated with over 1,000% higher efficiency than negative controls (F2408 cells). Sublines, 0.3--2.0 mm in diameter, were isolated and transferred to Leighton tubes in which they underwent an additional 0--7 divisions before senescence after 39--44 total population doublings. Subline phenotype was identical to the original parental phenotype, including epithelioid morphology, organized pattern of growth, extreme sensitivity to density-dependent inhibition of growth, and continuous production of infectious SV40 as detected by the combined tests of cocultivation and direct isolation. Limited division potential was within the range observed for the parental line. The ability to grow in agar without identifiable phenotypic changes was therefore confirmed for this line of SV40-transformed human epithelioid cells."}
{"id": "PMID:212574", "title": "Suppression of the hypothalamic-pituitary-adrenal axis after oral hydrocortisone succinate ingestion in rats.", "content": "Groups of Holtzman female rats were fed 10 mg/day of hydrocortisone succinate orally to study the responsiveness of the hypothalamic-pituitary-adrenal axis to acute stress. Pituitary ACTH content, plasma ACTH, adrenal venous corticosterone, and adrenal weights were studied simultaneously in experimental and control rats before, during, and up to two weeks after oral hydrocortisone administration. There was a significant decrease in pituitary ACTH content (p=<0.001), suppression of plasma ACTH and corticosterone in response to acute stress (p=<0.001), and adrenal atrophy during and following oral hydrocortisone administration. After discontinuing the hydrocortisone it required three to five days for the rats to respond adequately to acute stress. However, it was seven to ten days post-hydrocortisone before plasma ACTH and corticosterone responses to acute stress had returned to basal values, but decreased pituitary ACTH content and partial adrenal atrophy continued throughout the ten-day post-hydrocortisone study interval. Recovering from the suppressive effects of oral hydrocortisone was more rapid than following parenteral hydrocortisone. However, oral hydrocortisone causes identical but less sustained suppression of the hypothalamic-pituitary-adrenal axis as observed in animals treated with parenteral glucocorticoid preparations.", "contents": "Suppression of the hypothalamic-pituitary-adrenal axis after oral hydrocortisone succinate ingestion in rats. Groups of Holtzman female rats were fed 10 mg/day of hydrocortisone succinate orally to study the responsiveness of the hypothalamic-pituitary-adrenal axis to acute stress. Pituitary ACTH content, plasma ACTH, adrenal venous corticosterone, and adrenal weights were studied simultaneously in experimental and control rats before, during, and up to two weeks after oral hydrocortisone administration. There was a significant decrease in pituitary ACTH content (p=<0.001), suppression of plasma ACTH and corticosterone in response to acute stress (p=<0.001), and adrenal atrophy during and following oral hydrocortisone administration. After discontinuing the hydrocortisone it required three to five days for the rats to respond adequately to acute stress. However, it was seven to ten days post-hydrocortisone before plasma ACTH and corticosterone responses to acute stress had returned to basal values, but decreased pituitary ACTH content and partial adrenal atrophy continued throughout the ten-day post-hydrocortisone study interval. Recovering from the suppressive effects of oral hydrocortisone was more rapid than following parenteral hydrocortisone. However, oral hydrocortisone causes identical but less sustained suppression of the hypothalamic-pituitary-adrenal axis as observed in animals treated with parenteral glucocorticoid preparations."}
{"id": "PMID:212575", "title": "Endocrine function in a patient with asymmetrical acral hypertrophy and giantism: a possible variant of the Kippel-Trenaunay syndrome.", "content": "Endocrine function was evaluated in a 38-year-old man who had patchy asymmetrical acral hypertrophy and giantism. The history and clinical manifestations were consistent with previously described cases of the Klippel-Trenaunay syndrome. Pituitary and peripheral hormone concentrations were generally elevated, but his endocrine status appeared normal by clinical evaluation. Of particular interest were elevated growth hormone and somatomedin-A concentrations and responses to provocative tests. These findings suggest that this patient had abnormal cell receptor pathophysiology as the cause of the asymmetrical acral hypertrophy and giantism, which often occurred in the same anatomical site.", "contents": "Endocrine function in a patient with asymmetrical acral hypertrophy and giantism: a possible variant of the Kippel-Trenaunay syndrome. Endocrine function was evaluated in a 38-year-old man who had patchy asymmetrical acral hypertrophy and giantism. The history and clinical manifestations were consistent with previously described cases of the Klippel-Trenaunay syndrome. Pituitary and peripheral hormone concentrations were generally elevated, but his endocrine status appeared normal by clinical evaluation. Of particular interest were elevated growth hormone and somatomedin-A concentrations and responses to provocative tests. These findings suggest that this patient had abnormal cell receptor pathophysiology as the cause of the asymmetrical acral hypertrophy and giantism, which often occurred in the same anatomical site."}
{"id": "PMID:212576", "title": "env Gene of chicken RNA tumor viruses: extent of conservation in cellular and viral genomes.", "content": "The env gene of avian sarcoma-leukosis viruses codes for envelope glycoproteins that determine viral host range, antigenic specificity, and interference patterns. We used molecular hybridization to analyze the natural distribution and possible origins of the nucleotide sequences that encode env; our work exploited the availability of radioactive DNA (cDNA(gp)) complementary to most or all of env. env sequences were detectable in the DNAs of chickens which synthesized an env gene product (chick helper factor positive) encoded by an endogenous viral gene and also in the DNAs of chickens which synthesized little or no env gene product (chick helper factor negative). env sequences were not detectable in DNAs from Japanese quail, ring-necked pheasant, golden pheasant, duck, squab, salmon sperm, or calf thymus. The detection of sequences closely related to viral env only in chicken DNA contrasts sharply with the demonstration that the transforming gene (src) of avian sarcoma viruses has readily detectable homologues in the DNAs of all avian species tested [D. Stehelin, H. E. Varmus, J. M. Bishop, and P. K. Vogt, Nature (London) 260: 170-173, 1976] and in the DNAs of other vertebrates (D. Spector, personal communication). Thermal denaturation studies on duplexes formed between cDNA(gp) and chicken DNA and also between cDNA(gp) and RNAs of subgroup A to E viruses derived from chickens indicated that these duplexes were well matched. In contrast, cDNA(gp) did not form stable hybrids with RNAs of viruses which were isolated from ring-necked and golden pheasants. We conclude that substantial portions of nucleotide sequences within the env genes of viruses of subgroups A to E are closely related and that these genes probably have a common, perhaps cellular, evolutionary origin.", "contents": "env Gene of chicken RNA tumor viruses: extent of conservation in cellular and viral genomes. The env gene of avian sarcoma-leukosis viruses codes for envelope glycoproteins that determine viral host range, antigenic specificity, and interference patterns. We used molecular hybridization to analyze the natural distribution and possible origins of the nucleotide sequences that encode env; our work exploited the availability of radioactive DNA (cDNA(gp)) complementary to most or all of env. env sequences were detectable in the DNAs of chickens which synthesized an env gene product (chick helper factor positive) encoded by an endogenous viral gene and also in the DNAs of chickens which synthesized little or no env gene product (chick helper factor negative). env sequences were not detectable in DNAs from Japanese quail, ring-necked pheasant, golden pheasant, duck, squab, salmon sperm, or calf thymus. The detection of sequences closely related to viral env only in chicken DNA contrasts sharply with the demonstration that the transforming gene (src) of avian sarcoma viruses has readily detectable homologues in the DNAs of all avian species tested [D. Stehelin, H. E. Varmus, J. M. Bishop, and P. K. Vogt, Nature (London) 260: 170-173, 1976] and in the DNAs of other vertebrates (D. Spector, personal communication). Thermal denaturation studies on duplexes formed between cDNA(gp) and chicken DNA and also between cDNA(gp) and RNAs of subgroup A to E viruses derived from chickens indicated that these duplexes were well matched. In contrast, cDNA(gp) did not form stable hybrids with RNAs of viruses which were isolated from ring-necked and golden pheasants. We conclude that substantial portions of nucleotide sequences within the env genes of viruses of subgroups A to E are closely related and that these genes probably have a common, perhaps cellular, evolutionary origin."}
{"id": "PMID:212577", "title": "Effects of adenine arabinoside on lymphocytes infected with Epstein-Barr virus.", "content": "Low concentrations of adenine arabinoside inhibited growth of two Epstein-Barr virus producer cell lines in culture, while not significantly affecting a nonproducer cell line and a B-cell-negative line. These observations were extended to include freshly infected cells. Mitogen-stimulated human umbilical cord blood lymphocytes were unaffected by the drug at concentration levels that inhibited [3H]thymidine incorporation into the DNA of Epstein-Barr virus-stimulated cells. DNA synthesis in Epstein-Barr virus-superinfected Raji cells was also adversely affected by adenine arabinoside. However, these same low concentrations of adenine arabinoside in the triphosphate form produced less effect on DNA synthesis in nuclear systems and DNA polymerase assays than on growth or DNA synthesis in whole cells. Therefore the effects reported here of low concentrations of the drug on whole cells may be only in part related to DNA polymerase inhibition. The work reported here suggests that adenine arabinoside has multiple sites of action in infected cells.", "contents": "Effects of adenine arabinoside on lymphocytes infected with Epstein-Barr virus. Low concentrations of adenine arabinoside inhibited growth of two Epstein-Barr virus producer cell lines in culture, while not significantly affecting a nonproducer cell line and a B-cell-negative line. These observations were extended to include freshly infected cells. Mitogen-stimulated human umbilical cord blood lymphocytes were unaffected by the drug at concentration levels that inhibited [3H]thymidine incorporation into the DNA of Epstein-Barr virus-stimulated cells. DNA synthesis in Epstein-Barr virus-superinfected Raji cells was also adversely affected by adenine arabinoside. However, these same low concentrations of adenine arabinoside in the triphosphate form produced less effect on DNA synthesis in nuclear systems and DNA polymerase assays than on growth or DNA synthesis in whole cells. Therefore the effects reported here of low concentrations of the drug on whole cells may be only in part related to DNA polymerase inhibition. The work reported here suggests that adenine arabinoside has multiple sites of action in infected cells."}
{"id": "PMID:212578", "title": "Collaborative complementation study of temperature-sensitive mutants of herpes simplex virus types 1 and 2.", "content": "Twenty-three complementation groups of herpes simplex virus type 1 (HSV-1) and 20 of HSV-2 were identified by qualitative and quantitative complementation analysis from among 43 temperature-sensitive (ts) mutants of HSV-1 and 29 ts mutants of HSV-2 which had been isolated independently in 10 laboratories.", "contents": "Collaborative complementation study of temperature-sensitive mutants of herpes simplex virus types 1 and 2. Twenty-three complementation groups of herpes simplex virus type 1 (HSV-1) and 20 of HSV-2 were identified by qualitative and quantitative complementation analysis from among 43 temperature-sensitive (ts) mutants of HSV-1 and 29 ts mutants of HSV-2 which had been isolated independently in 10 laboratories."}
{"id": "PMID:212579", "title": "Timing of some of the molecular events required for cell fusion induced by herpes simplex virus type 1.", "content": "The timing of some of the molecular events that are required for cell fusion was investigated. Cell fusion was produced by a mutant of herpes simplex virus type 1 that causes extensive cell fusion during infection. The timing of molecular events required for fusion was established by the use of blocking agents. Phosphonoacetic acid blocks viral DNA synthesis; actinomycin D blocks RNA synthesis; cycloheximide blocks protein synthesis; 2-deoxyglucose blocks glycosylation of glycoproteins; high temperature, NH(4)Cl, and adamantanone block unknown steps required for cell fusion. For cells infected at a low multiplicity of infection, phosphonoacetic acid decreased the rate but not the final amount of fusion, but at a multiplicity of infection of 10 it had no effect on the rate of cell fusion. RNA synthesis was required for fusion until 4 h after infection, protein synthesis until 5.5 h after infection, and glycosylation until 7 h after infection. The temperature-dependent step occurred before 6 h after infection, whereas NH(4)Cl and adamantanone acted at steps that occurred until 8 h after infection. Cycloheximide, temperature, NH(4)Cl, and adamantanone acted reversibly; actinomycin D and 2-deoxyglucose acted irreversibly. The same order of action of the inhibitors was also determined by using pairs of inhibitors sequentially. These experiments also indicated that the fusion factor was not an alpha-polypeptide. Virus growth and cell fusion were both found to be highly dependent on temperature in the range of 30 to 40 degrees C. Wild-type infections are apparently characterized by the presence of a fusion factor and a fusion inhibitor. The fusion-blocking agents were added to wild-type-infected cells under a variety of conditions in an attempt to selectively block the production of the fusion inhibitor molecule and thereby cause extensive cell fusion. However, fusion was not observed in any of these experiments.", "contents": "Timing of some of the molecular events required for cell fusion induced by herpes simplex virus type 1. The timing of some of the molecular events that are required for cell fusion was investigated. Cell fusion was produced by a mutant of herpes simplex virus type 1 that causes extensive cell fusion during infection. The timing of molecular events required for fusion was established by the use of blocking agents. Phosphonoacetic acid blocks viral DNA synthesis; actinomycin D blocks RNA synthesis; cycloheximide blocks protein synthesis; 2-deoxyglucose blocks glycosylation of glycoproteins; high temperature, NH(4)Cl, and adamantanone block unknown steps required for cell fusion. For cells infected at a low multiplicity of infection, phosphonoacetic acid decreased the rate but not the final amount of fusion, but at a multiplicity of infection of 10 it had no effect on the rate of cell fusion. RNA synthesis was required for fusion until 4 h after infection, protein synthesis until 5.5 h after infection, and glycosylation until 7 h after infection. The temperature-dependent step occurred before 6 h after infection, whereas NH(4)Cl and adamantanone acted at steps that occurred until 8 h after infection. Cycloheximide, temperature, NH(4)Cl, and adamantanone acted reversibly; actinomycin D and 2-deoxyglucose acted irreversibly. The same order of action of the inhibitors was also determined by using pairs of inhibitors sequentially. These experiments also indicated that the fusion factor was not an alpha-polypeptide. Virus growth and cell fusion were both found to be highly dependent on temperature in the range of 30 to 40 degrees C. Wild-type infections are apparently characterized by the presence of a fusion factor and a fusion inhibitor. The fusion-blocking agents were added to wild-type-infected cells under a variety of conditions in an attempt to selectively block the production of the fusion inhibitor molecule and thereby cause extensive cell fusion. However, fusion was not observed in any of these experiments."}
{"id": "PMID:212580", "title": "Involvement of mouse mammary tumor virus in spontaneous and hormone-induced mammary tumors in low-mammary-tumor mouse strains.", "content": "The involvement of the mouse mammary tumor virus (MTV) in spontaneous and hormone-induced mammary tumors in low-mammary-tumor mouse strains was studied by comparing the amounts of MTV RNA and MTV DNA sequences in mammary tumors and other tissues of mice with an without hormonal treatments. The following results were obtained. (i) Mammary tumors which appeared in C3H mice as a result of an infection with MTV contained more MTV DNA compared with noninfected organs; these mammary tumors also contained more MTV RNA than was present in lactating mammary gland cells. (ii) Hormonal stimulation by administration of excessive amounts of prolactin via hypophyseal isografts in C3Hf and O20 mice resulted in an increased expression of MTV RNA in the mammary glands. This elevated level of MTV RNA expression was, however, not maintained in the hormone-induced mammary tumors. (iii) Spontaneous mammary tumors in BALB/c mice contained similar levels of MTV DNA and MTV RNA sequences as were found in other cells of these animals.", "contents": "Involvement of mouse mammary tumor virus in spontaneous and hormone-induced mammary tumors in low-mammary-tumor mouse strains. The involvement of the mouse mammary tumor virus (MTV) in spontaneous and hormone-induced mammary tumors in low-mammary-tumor mouse strains was studied by comparing the amounts of MTV RNA and MTV DNA sequences in mammary tumors and other tissues of mice with an without hormonal treatments. The following results were obtained. (i) Mammary tumors which appeared in C3H mice as a result of an infection with MTV contained more MTV DNA compared with noninfected organs; these mammary tumors also contained more MTV RNA than was present in lactating mammary gland cells. (ii) Hormonal stimulation by administration of excessive amounts of prolactin via hypophyseal isografts in C3Hf and O20 mice resulted in an increased expression of MTV RNA in the mammary glands. This elevated level of MTV RNA expression was, however, not maintained in the hormone-induced mammary tumors. (iii) Spontaneous mammary tumors in BALB/c mice contained similar levels of MTV DNA and MTV RNA sequences as were found in other cells of these animals."}
{"id": "PMID:212581", "title": "Rebinding of transcriptase components (L and NS proteins) to the nucleocapsid template of vesicular stomatitis virus.", "content": "The L and NS proteins of vesicular stomatitis virions (New Jersey serotype) were solubilized with Triton X-100 and high-salt buffer and recombined with purified nucleocapsids under conditions similar to those used to reconstitute transcriptase activity in vitro. The nucleocapsid-bound L and NS proteins were separated from unbound proteins on a glycerol gradient. The rebinding of L and NS proteins mimics the in vivo binding in that at saturation the ratio of L and NS molecules to N molecules is approximately the same as observed in the intact virion. L and NS proteins were separated and added back independently and in combination to the template. The purified NS protein bound to the template in the absence of L protein. However, the L protein binding appeared to depend on the presence of NS protein. The presence of Mg2+ and nucleotides, which is required for transcription, was not necessary for the rebinding of L and NS proteins.", "contents": "Rebinding of transcriptase components (L and NS proteins) to the nucleocapsid template of vesicular stomatitis virus. The L and NS proteins of vesicular stomatitis virions (New Jersey serotype) were solubilized with Triton X-100 and high-salt buffer and recombined with purified nucleocapsids under conditions similar to those used to reconstitute transcriptase activity in vitro. The nucleocapsid-bound L and NS proteins were separated from unbound proteins on a glycerol gradient. The rebinding of L and NS proteins mimics the in vivo binding in that at saturation the ratio of L and NS molecules to N molecules is approximately the same as observed in the intact virion. L and NS proteins were separated and added back independently and in combination to the template. The purified NS protein bound to the template in the absence of L protein. However, the L protein binding appeared to depend on the presence of NS protein. The presence of Mg2+ and nucleotides, which is required for transcription, was not necessary for the rebinding of L and NS proteins."}
{"id": "PMID:212582", "title": "Poliovirus single-stranded RNA and double-stranded RNA: differential infectivity in enucleate cells.", "content": "The ability of poliovirus virion RNA and double-stranded RNA (replicative form) to replicate in enucleate mouse L cells was investigated. Virion RNA replicated successfully in the absence of the cell nucleus, whereas replicative form infection did not produce any detectable progeny in enucleate cells. The results provide direct evidence of a nuclear requirement early in the infection initiated by replicative form RNA.", "contents": "Poliovirus single-stranded RNA and double-stranded RNA: differential infectivity in enucleate cells. The ability of poliovirus virion RNA and double-stranded RNA (replicative form) to replicate in enucleate mouse L cells was investigated. Virion RNA replicated successfully in the absence of the cell nucleus, whereas replicative form infection did not produce any detectable progeny in enucleate cells. The results provide direct evidence of a nuclear requirement early in the infection initiated by replicative form RNA."}
{"id": "PMID:212583", "title": "Purification of the Epstein-Barr virus-determined nuclear antigen from Epstein-Barr virus-transformed human lymphoid cell lines.", "content": "The Epstein-Barr virus-determined nuclear antigen (EBNA) was purified from extracts of the human lymphoid cell lines Raji, Namalwa, and B95-8/MLD by two different methods. In the first approach, the apparently native antigen was purified 1,200-fold by a four-step procedure involving DNA-cellulose chromatography, blue dexptran-agarose chromatography, hydroxyapatite chromatography, and gel filtration, employing complement fixation as the assay procedure. Such EBNA preparations specifically inhibited the anticomplement immunofluorescence test for EBNA and bound to methanol/acetic acid-fixed metaphase chromosomes. The purified antigen, which has a molecular weight of 170,000 to 200,000, yielded a single protein band of molecular weight about 48,000 by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. These data indicate that native EBNA has a tetrameric structure. In the second purification method, EBNA-containing cell extracts containing radioactively labeled proteins were incubated with anti-EBNA-positive sera, and antigen-antibody complexes were adsorbed to matrix-bound staphylococcal protein A. The bound proteins were then released with an SDS-containing buffer, and denatured EBNA was separated from antibody chains by SDS-polyacrylamide gel electrophoresis and visualized by fluorography. The denatured EBNA obtained in radiochemically pure form by this procedure has a molecular weight of about 48,000, so both methods yield an EBNA monomer of the same size.", "contents": "Purification of the Epstein-Barr virus-determined nuclear antigen from Epstein-Barr virus-transformed human lymphoid cell lines. The Epstein-Barr virus-determined nuclear antigen (EBNA) was purified from extracts of the human lymphoid cell lines Raji, Namalwa, and B95-8/MLD by two different methods. In the first approach, the apparently native antigen was purified 1,200-fold by a four-step procedure involving DNA-cellulose chromatography, blue dexptran-agarose chromatography, hydroxyapatite chromatography, and gel filtration, employing complement fixation as the assay procedure. Such EBNA preparations specifically inhibited the anticomplement immunofluorescence test for EBNA and bound to methanol/acetic acid-fixed metaphase chromosomes. The purified antigen, which has a molecular weight of 170,000 to 200,000, yielded a single protein band of molecular weight about 48,000 by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. These data indicate that native EBNA has a tetrameric structure. In the second purification method, EBNA-containing cell extracts containing radioactively labeled proteins were incubated with anti-EBNA-positive sera, and antigen-antibody complexes were adsorbed to matrix-bound staphylococcal protein A. The bound proteins were then released with an SDS-containing buffer, and denatured EBNA was separated from antibody chains by SDS-polyacrylamide gel electrophoresis and visualized by fluorography. The denatured EBNA obtained in radiochemically pure form by this procedure has a molecular weight of about 48,000, so both methods yield an EBNA monomer of the same size."}
{"id": "PMID:212584", "title": "Intracellular restriction of ecotropic murine leukemia virus in rat NRK cells and its abolishment by adaptation.", "content": "Ecotropic murine leukemia viruses, both N-tropic FN-2 (purified helper component of Friend leukemia virus) and B-tropic WNB-2 (purified WN1802B BALB/c-derived endogenous virus), were partially restricted in rat NRK cells. In NRK cells, they produced obscure small plaques at reduced efficiencies relative to their plaque-producing efficiencies in mouse SC-1 cells (10-fold for FN-2 and 100-fold for WNB-2). After three or four passages in NRK cells, the plaquing efficiencies of the viruses in NRK cells increased to levels close to their efficiencies in mouse cells, and the plaques in NRK cells became larger and clearer. The adaptation was more complete with FN-2 than with WNB-2. The adaptation was not due to simple selection of a virus in the FN-2 stock, but was host induced, as the viruses had been submitted to successive limiting dilutions in SC-1 cells before propagation in NRK cells. Possible commitment of xenotropic virus in the adaptation was excluded. The change was stable, even if the adapted viruses were propagated back into SC-1 cells. The NRK-adapted viruses were restricted in other rat cell lines of different origins, and the virus adapted in another rat cell line, RFL, was still restricted in NRK cells. The adaptation was mainly brought about by increased viral growth within the rat cells and not by an increased efficiency of viral penetration into the rat cells. This inversely suggests that the restriction of the ecotropic murine leukemia viruses in NRK cells was a mainly intracellular event. The mobilities of gp69/71 and p30 in sodium dodecyl sulfatepolyacrylamide gel electrophoresis remained unchanged after adaptation of FN-2 in NRK cells.", "contents": "Intracellular restriction of ecotropic murine leukemia virus in rat NRK cells and its abolishment by adaptation. Ecotropic murine leukemia viruses, both N-tropic FN-2 (purified helper component of Friend leukemia virus) and B-tropic WNB-2 (purified WN1802B BALB/c-derived endogenous virus), were partially restricted in rat NRK cells. In NRK cells, they produced obscure small plaques at reduced efficiencies relative to their plaque-producing efficiencies in mouse SC-1 cells (10-fold for FN-2 and 100-fold for WNB-2). After three or four passages in NRK cells, the plaquing efficiencies of the viruses in NRK cells increased to levels close to their efficiencies in mouse cells, and the plaques in NRK cells became larger and clearer. The adaptation was more complete with FN-2 than with WNB-2. The adaptation was not due to simple selection of a virus in the FN-2 stock, but was host induced, as the viruses had been submitted to successive limiting dilutions in SC-1 cells before propagation in NRK cells. Possible commitment of xenotropic virus in the adaptation was excluded. The change was stable, even if the adapted viruses were propagated back into SC-1 cells. The NRK-adapted viruses were restricted in other rat cell lines of different origins, and the virus adapted in another rat cell line, RFL, was still restricted in NRK cells. The adaptation was mainly brought about by increased viral growth within the rat cells and not by an increased efficiency of viral penetration into the rat cells. This inversely suggests that the restriction of the ecotropic murine leukemia viruses in NRK cells was a mainly intracellular event. The mobilities of gp69/71 and p30 in sodium dodecyl sulfatepolyacrylamide gel electrophoresis remained unchanged after adaptation of FN-2 in NRK cells."}
{"id": "PMID:212585", "title": "Requirement of protein synthesis for the degradation of host mRNA in Friend erythroleukemia cells infected wtih herpes simplex virus type 1.", "content": "We describe experiments which demonstrate that shortly after infection of Friend erythroleukemia cells with herpes simplex virus (HSV), polyribosomes dissociate and cellular mRNA degrades. Analysis of infected cell extracts on sucrose density gradients demonstrates that the majority of the polyribosomes have dissociated to monoribosomes at 2 h postinfection. Physical measurements of infected-cell RNAs support this conclusion and demonstrate that the polyadenylated RNAs decrease in size. The degradation of mRNA is apparently a stochastic process as judged by the failure to detect a shift in the Crt1/2 when polyadenylated RNA extracted from infected cells at different times is hybridized to globin complementary DNA. In experiments designed to determine whether dissociation of polyribosomes is sufficient to cause degradation of globin mRNA, the amount of globin mRNA in uninfected cells did not change when cells were treated with NaF or pactamycin at concentrations sufficient to dissociate all polyribosomes. In cells infected with UV-irradiated virus polyribosomes dissociate but globin mRNA does not degrade, suggesting that it is possible to separate dissociation from degradation.", "contents": "Requirement of protein synthesis for the degradation of host mRNA in Friend erythroleukemia cells infected wtih herpes simplex virus type 1. We describe experiments which demonstrate that shortly after infection of Friend erythroleukemia cells with herpes simplex virus (HSV), polyribosomes dissociate and cellular mRNA degrades. Analysis of infected cell extracts on sucrose density gradients demonstrates that the majority of the polyribosomes have dissociated to monoribosomes at 2 h postinfection. Physical measurements of infected-cell RNAs support this conclusion and demonstrate that the polyadenylated RNAs decrease in size. The degradation of mRNA is apparently a stochastic process as judged by the failure to detect a shift in the Crt1/2 when polyadenylated RNA extracted from infected cells at different times is hybridized to globin complementary DNA. In experiments designed to determine whether dissociation of polyribosomes is sufficient to cause degradation of globin mRNA, the amount of globin mRNA in uninfected cells did not change when cells were treated with NaF or pactamycin at concentrations sufficient to dissociate all polyribosomes. In cells infected with UV-irradiated virus polyribosomes dissociate but globin mRNA does not degrade, suggesting that it is possible to separate dissociation from degradation."}
{"id": "PMID:212586", "title": "Comparison of initiation rates of encephalomyocarditis virus and host protein synthesis in infected cells.", "content": "The relative initiation rates for encephalomyocarditis virus mRNA and host mRNA's in infected cells were measured using two independent techniques. In both cases the results showed that viral mRNA initiates at a much higher rate than host mRNA'S. This difference was observed midway in the infectious cycle, well before virus-induced cytopathic effects (leakage of low-molecular-weight metabolites, failure to exclude trypan blue) were apparent. These results confirm that encephalomyocarditis viral mRNA is a more efficient initiator than host mRNA's in vivo, as has previously been demonstrated in in vitro experiments.", "contents": "Comparison of initiation rates of encephalomyocarditis virus and host protein synthesis in infected cells. The relative initiation rates for encephalomyocarditis virus mRNA and host mRNA's in infected cells were measured using two independent techniques. In both cases the results showed that viral mRNA initiates at a much higher rate than host mRNA'S. This difference was observed midway in the infectious cycle, well before virus-induced cytopathic effects (leakage of low-molecular-weight metabolites, failure to exclude trypan blue) were apparent. These results confirm that encephalomyocarditis viral mRNA is a more efficient initiator than host mRNA's in vivo, as has previously been demonstrated in in vitro experiments."}
{"id": "PMID:212587", "title": "Specificity of interferon action in protein synthesis.", "content": "Inhibitors of elongation steps in protein synthesis such as cycloheximide and anisomycin mimic interferon treatment in that they specifically inhibit the synthesis of certain viral proteins. These specific effects are seen only at very low concentrations of the antibiotics, under conditions where host cellular protein synthesis, as well as cell viability, are not severely reduced. A qualitatively as well as quantitatively close correlation between the effects of the two types of agents has been established for encephalomyocarditis virus, vesicular stomatitis virus and murine leukemia virus protein synthesis. It is concluded that one of the primary mechanisms of interferon action may be a nonspecific retardation of one or more elongation steps, and that this may be sufficient to account for its effects on the replication of certain viruses such as encephalomyocarditis and vesicular stomatitis viruses.", "contents": "Specificity of interferon action in protein synthesis. Inhibitors of elongation steps in protein synthesis such as cycloheximide and anisomycin mimic interferon treatment in that they specifically inhibit the synthesis of certain viral proteins. These specific effects are seen only at very low concentrations of the antibiotics, under conditions where host cellular protein synthesis, as well as cell viability, are not severely reduced. A qualitatively as well as quantitatively close correlation between the effects of the two types of agents has been established for encephalomyocarditis virus, vesicular stomatitis virus and murine leukemia virus protein synthesis. It is concluded that one of the primary mechanisms of interferon action may be a nonspecific retardation of one or more elongation steps, and that this may be sufficient to account for its effects on the replication of certain viruses such as encephalomyocarditis and vesicular stomatitis viruses."}
{"id": "PMID:212588", "title": "Characterization of the env gene in avian oncoviruses by heteroduplex mapping.", "content": "The genome of ring-necked pheasant virus, an avian oncovirus, is largely homologous to the genomes of chicken oncoviruses except for a specific nonhomology in env, the gene coding for the surface glycoprotein of the virion (J. Tal, D. J. Fujita, S. Kawai, H. E. Varmus, and J. M. Bishop, J. Virol. 21:497--505, 1977). We have used this nonhomology between ring-necked pheasant virus and chicken oncoviruses in electron microscopic studies of heteroduplex molecules. The env-specific region of nonhomology is 1.5 to 1.7 kilobases in length. Its 3' boundary is located 0.6 to 0.7 kilobases from the 3' end of the genome in transformation-defective viruses and 2.5 kilobases from the 3' end in nondefective avian sarcoma viruses. Comparison of several strains of avian oncoviruses shows that the 3' half of this env region is conserved, while the 5' half is more diverged. A small area at the very 3' end of env also shows divergence between different avian oncoviruses. We found no evidence for the presence of a previously unrecognized gene between env and src. An electrophoretic comparison of the glycoproteins from various avian oncoviruses shows that those of ring-necked pheasant virus and Chinese quail virus differ in molecular weight from the glycoproteins of the chicken oncoviruses.", "contents": "Characterization of the env gene in avian oncoviruses by heteroduplex mapping. The genome of ring-necked pheasant virus, an avian oncovirus, is largely homologous to the genomes of chicken oncoviruses except for a specific nonhomology in env, the gene coding for the surface glycoprotein of the virion (J. Tal, D. J. Fujita, S. Kawai, H. E. Varmus, and J. M. Bishop, J. Virol. 21:497--505, 1977). We have used this nonhomology between ring-necked pheasant virus and chicken oncoviruses in electron microscopic studies of heteroduplex molecules. The env-specific region of nonhomology is 1.5 to 1.7 kilobases in length. Its 3' boundary is located 0.6 to 0.7 kilobases from the 3' end of the genome in transformation-defective viruses and 2.5 kilobases from the 3' end in nondefective avian sarcoma viruses. Comparison of several strains of avian oncoviruses shows that the 3' half of this env region is conserved, while the 5' half is more diverged. A small area at the very 3' end of env also shows divergence between different avian oncoviruses. We found no evidence for the presence of a previously unrecognized gene between env and src. An electrophoretic comparison of the glycoproteins from various avian oncoviruses shows that those of ring-necked pheasant virus and Chinese quail virus differ in molecular weight from the glycoproteins of the chicken oncoviruses."}
{"id": "PMID:212589", "title": "Strain-specific markers for the major structural proteins of highly oncogenic murine mammary tumor viruses by tryptic peptide analyses.", "content": "Tryptic peptide analyses were performed on the major structural 52,000- and 36,000-dalton glycoproteins (gp52 and gp36-38) and the nonglycosylated 28,000-, 14,000-, and 10,000-dalton proteins (p28, p14, and p10) of the highly oncogenic murine mammary tumor viruses (MMTVs) of C3H, RIII, and GR mice, i.e., MMTV(C3H), MMTV(RIII), and MMTV(GR), respectively. Each virus was grown in both murine and feline cells to ensure the virus-coded nature of each peptide analyzed. The gp36-38 peptide maps of all three MMTVs were indistinguishable, as were the p14 maps of the different MMTVs. Both the p28 and the gp52 of MMTV(C3H), however, could be clearly distinguished from the corresponding proteins of MMTV(RIII) and MMTV(GR), regardless of whether the viruses were grown in feline or murine cells. The p1o of MMTV(RIII) was clearly different from that of MMTV(C3H) and MMTV(GR). Therefore, tryptic peptide analysis of three proteins, gp52, p28, and p10, can serve to distinguish these three viruses from one another. These studies further characterize the heterogeneity in polypeptides among MMTVs.", "contents": "Strain-specific markers for the major structural proteins of highly oncogenic murine mammary tumor viruses by tryptic peptide analyses. Tryptic peptide analyses were performed on the major structural 52,000- and 36,000-dalton glycoproteins (gp52 and gp36-38) and the nonglycosylated 28,000-, 14,000-, and 10,000-dalton proteins (p28, p14, and p10) of the highly oncogenic murine mammary tumor viruses (MMTVs) of C3H, RIII, and GR mice, i.e., MMTV(C3H), MMTV(RIII), and MMTV(GR), respectively. Each virus was grown in both murine and feline cells to ensure the virus-coded nature of each peptide analyzed. The gp36-38 peptide maps of all three MMTVs were indistinguishable, as were the p14 maps of the different MMTVs. Both the p28 and the gp52 of MMTV(C3H), however, could be clearly distinguished from the corresponding proteins of MMTV(RIII) and MMTV(GR), regardless of whether the viruses were grown in feline or murine cells. The p1o of MMTV(RIII) was clearly different from that of MMTV(C3H) and MMTV(GR). Therefore, tryptic peptide analysis of three proteins, gp52, p28, and p10, can serve to distinguish these three viruses from one another. These studies further characterize the heterogeneity in polypeptides among MMTVs."}
{"id": "PMID:212590", "title": "Cleavage map of BK virus DNA with restriction endonucleases MboI and HaeIII.", "content": "Specific cleavage of BK virus (MM) DNA with restriction endonuclease MboI gives rise to 10 fragments. Two techniques were used to determine the location of these fragments on the viral genome with respect to the three known sites for HindIII cleavage. In the first method, reciprocal digestion, individual MboI fragments were digested with HindIII and individual HindIII fragments were digested with MboI. In the second method, single-end 32P-labeled HindIII subfragments were partially digested with MboI, and then the sizes of the radioactive partial products were used to deduce the nearest neighboring fragment. Information from these two methods is more than adequate to map all the MboI enzyme sites. Cleavage of BK virus (MM) DNA with restriction enzyme HaeIII produces 21 fragments. With the aid of the same two methods, these fragments have also been ordered with respect to the known map locations of the HindIII and MboI sites.", "contents": "Cleavage map of BK virus DNA with restriction endonucleases MboI and HaeIII. Specific cleavage of BK virus (MM) DNA with restriction endonuclease MboI gives rise to 10 fragments. Two techniques were used to determine the location of these fragments on the viral genome with respect to the three known sites for HindIII cleavage. In the first method, reciprocal digestion, individual MboI fragments were digested with HindIII and individual HindIII fragments were digested with MboI. In the second method, single-end 32P-labeled HindIII subfragments were partially digested with MboI, and then the sizes of the radioactive partial products were used to deduce the nearest neighboring fragment. Information from these two methods is more than adequate to map all the MboI enzyme sites. Cleavage of BK virus (MM) DNA with restriction enzyme HaeIII produces 21 fragments. With the aid of the same two methods, these fragments have also been ordered with respect to the known map locations of the HindIII and MboI sites."}
{"id": "PMID:212591", "title": "Identification of a herpesvirus isolated from cytomegalovirus-transformed human cells.", "content": "Human cells transformed by cytomegalovirus and transplanted to athymic nude mice yielded a cytopathic virus, Hershey Medical Center virus, following prolonged in vitro passage of the tumor cells. The virus is a double-enveloped herpesvirus, is sensitive to ether, and is inhibited by iododeoxyuridine. No significant antigenic relationship to herpes simplex virus was detected using herpes simplex virus-immune sera in neutralization and immunofluorescence tests, but indirect immunofluorescence tests revealed cytomegalovirus-related antigenicity. Further immunological tests revealed that Hershey Medical Center virus is antigenically indistinguishable from infectious bovine rhinotracheitis virus. Thus, it appears that Hershey Medical Center virus is infectious bovine rhinotracheitis virus, which presumably appeared in the cell culture as a contaminant from fetal calf serum.", "contents": "Identification of a herpesvirus isolated from cytomegalovirus-transformed human cells. Human cells transformed by cytomegalovirus and transplanted to athymic nude mice yielded a cytopathic virus, Hershey Medical Center virus, following prolonged in vitro passage of the tumor cells. The virus is a double-enveloped herpesvirus, is sensitive to ether, and is inhibited by iododeoxyuridine. No significant antigenic relationship to herpes simplex virus was detected using herpes simplex virus-immune sera in neutralization and immunofluorescence tests, but indirect immunofluorescence tests revealed cytomegalovirus-related antigenicity. Further immunological tests revealed that Hershey Medical Center virus is antigenically indistinguishable from infectious bovine rhinotracheitis virus. Thus, it appears that Hershey Medical Center virus is infectious bovine rhinotracheitis virus, which presumably appeared in the cell culture as a contaminant from fetal calf serum."}
{"id": "PMID:212592", "title": "Viral gene expression in murine sarcoma virus(murine leukemia virus)-infected cells.", "content": "NIH 3T3 cells infected with Moloney murine sarcoma virus (murine leukemia virus) produce virions which contain about 99% murine sarcoma virus RNA and 1% murine leukemia virus RNA. This report describes experiments which measured intracellular concentrations of proviral DNA and RNA transcripts for each of the viruses. We found that three to four copies of proviral DNA from each virus were integrated into the cellular DNA. Measurements of RNA specific for each of the genomes by hybridization to specific cDNA reagents revealed a 10- to 15-fold difference in concentration in both nuclear and polysomal RNA fractions, with murine sarcoma virus RNA predominating in both cases. Unless there are major differences in stability between the two viral RNAs, our results suggest that transcriptional control is responsible for much of the difference in final levels of virus synthesis.", "contents": "Viral gene expression in murine sarcoma virus(murine leukemia virus)-infected cells. NIH 3T3 cells infected with Moloney murine sarcoma virus (murine leukemia virus) produce virions which contain about 99% murine sarcoma virus RNA and 1% murine leukemia virus RNA. This report describes experiments which measured intracellular concentrations of proviral DNA and RNA transcripts for each of the viruses. We found that three to four copies of proviral DNA from each virus were integrated into the cellular DNA. Measurements of RNA specific for each of the genomes by hybridization to specific cDNA reagents revealed a 10- to 15-fold difference in concentration in both nuclear and polysomal RNA fractions, with murine sarcoma virus RNA predominating in both cases. Unless there are major differences in stability between the two viral RNAs, our results suggest that transcriptional control is responsible for much of the difference in final levels of virus synthesis."}
{"id": "PMID:212593", "title": "In vitro synthesis of double-stranded DNA from the Kilham rat virus single-stranded DNA genome.", "content": "Double-stranded, full-length linear DNA was synthesized in vitro by using single-stranded linear DNA as a self-priming template from the parvovirus Kilham rat virus and Escherichia coli DNA polymerase \"large fragment\" as the polymerizing enzyme. To ascertain the order of the synthesis of the cleavage fragments and to assess the accuracy of the in vitro synthesis, restriction endonuclease cleavage sites with known recognition sequences were mapped on the DNA. Comparing the cleavage pattern of the synthesized DNA with that of double-stranded viral DNA isolated from infected cells confirms that the in vitro synthesis produces a faithful copy of the viral single-stranded genome. Electron micrographs of the in vitro product reveal it to be a double-stranded linear molecule.", "contents": "In vitro synthesis of double-stranded DNA from the Kilham rat virus single-stranded DNA genome. Double-stranded, full-length linear DNA was synthesized in vitro by using single-stranded linear DNA as a self-priming template from the parvovirus Kilham rat virus and Escherichia coli DNA polymerase \"large fragment\" as the polymerizing enzyme. To ascertain the order of the synthesis of the cleavage fragments and to assess the accuracy of the in vitro synthesis, restriction endonuclease cleavage sites with known recognition sequences were mapped on the DNA. Comparing the cleavage pattern of the synthesized DNA with that of double-stranded viral DNA isolated from infected cells confirms that the in vitro synthesis produces a faithful copy of the viral single-stranded genome. Electron micrographs of the in vitro product reveal it to be a double-stranded linear molecule."}
{"id": "PMID:212594", "title": "Phosphorylation of chromatin- and ribosome-associated proteins in cells transformed by adenovirus, murine sarcoma virus, and methylcholanthrene.", "content": "Endogenous protein phosphorylation in chromatin and ribosomes of monkey, mouse, and rat cells transformed by DNA, RNA tumor viruses, and a chemical carcinogen revealed the association of a protein of approximately 90,000 daltons (90K), which is highly phosphorylated in vitro. Peptide map analysis showed that the 90K proteins associated with these organelles of various transformed cells are similar irrespective of the species of cells and transforming agents. This species of protein could not be detected, or was scarcely detected, by phosphorylation in chromatin and ribosomes of untransformed cells and in revertants of transformed cells. These results suggest that the alteration in the pattern of endogenous protein phosphorylation in these organelles is closely related to the transformed state of cells.", "contents": "Phosphorylation of chromatin- and ribosome-associated proteins in cells transformed by adenovirus, murine sarcoma virus, and methylcholanthrene. Endogenous protein phosphorylation in chromatin and ribosomes of monkey, mouse, and rat cells transformed by DNA, RNA tumor viruses, and a chemical carcinogen revealed the association of a protein of approximately 90,000 daltons (90K), which is highly phosphorylated in vitro. Peptide map analysis showed that the 90K proteins associated with these organelles of various transformed cells are similar irrespective of the species of cells and transforming agents. This species of protein could not be detected, or was scarcely detected, by phosphorylation in chromatin and ribosomes of untransformed cells and in revertants of transformed cells. These results suggest that the alteration in the pattern of endogenous protein phosphorylation in these organelles is closely related to the transformed state of cells."}
{"id": "PMID:212595", "title": "Murine leukemia virus (T-8)-transformed cells: identification of a precursor polyprotein containing gag gene-coded proteins (p15 and p12) and a nonstructural component.", "content": "Mink cells nonproductively transformed by the T-8 strain of mink cell focus-inducing virus express two type C viral amino terminal gag gene-coded structural proteins, p15 and p12, in the form of a 90,000 to 110,000 molecular weight polyprotein that lacks detectable immunological reactivity with other known type C virus-coded translational products. The observation concurs with the previous demonstration of similar high-molecular-weight precursor polyproteins in cell lines nonproductively transformed by either of two other mammalian sarcoma viruses also limited in virus-coded structural protein expression to p15 and p12.", "contents": "Murine leukemia virus (T-8)-transformed cells: identification of a precursor polyprotein containing gag gene-coded proteins (p15 and p12) and a nonstructural component. Mink cells nonproductively transformed by the T-8 strain of mink cell focus-inducing virus express two type C viral amino terminal gag gene-coded structural proteins, p15 and p12, in the form of a 90,000 to 110,000 molecular weight polyprotein that lacks detectable immunological reactivity with other known type C virus-coded translational products. The observation concurs with the previous demonstration of similar high-molecular-weight precursor polyproteins in cell lines nonproductively transformed by either of two other mammalian sarcoma viruses also limited in virus-coded structural protein expression to p15 and p12."}
{"id": "PMID:212596", "title": "Growth control in simian virus 40-transformed rat cells: temperature-independent expression of the transformed phenotype in tsA transformants derived by agar selection.", "content": "Fisher rat fibroblasts (FR 3T3), transformed with the tsA30 mutant of simian virus 40 and selected by colony formation in soft agar, maintained the transformed phenotype at high temperature, whereas most transformants isolated from foci were found to undergo a phenotypic reversion toward the normal state in their saturation density, ability to grow in soft agar, and rate of 2-deoxyglucose transport. The temperature-independent phenotype observed in agar-selected transformants was not due to a reversion of the viral mutation. These results, similar to those previously obtained with polyoma virus tsa mutants, further suggest that two distinct mechanisms may operate in both cases for maintaining the transformed phenotype. Immunofluorescence studies suggested a different regulation of T antigen synthesis in these two classes of transformants.", "contents": "Growth control in simian virus 40-transformed rat cells: temperature-independent expression of the transformed phenotype in tsA transformants derived by agar selection. Fisher rat fibroblasts (FR 3T3), transformed with the tsA30 mutant of simian virus 40 and selected by colony formation in soft agar, maintained the transformed phenotype at high temperature, whereas most transformants isolated from foci were found to undergo a phenotypic reversion toward the normal state in their saturation density, ability to grow in soft agar, and rate of 2-deoxyglucose transport. The temperature-independent phenotype observed in agar-selected transformants was not due to a reversion of the viral mutation. These results, similar to those previously obtained with polyoma virus tsa mutants, further suggest that two distinct mechanisms may operate in both cases for maintaining the transformed phenotype. Immunofluorescence studies suggested a different regulation of T antigen synthesis in these two classes of transformants."}
{"id": "PMID:212597", "title": "Biochemical properties of p15-associated protease in an avian RNA tumor virus.", "content": "It was observed that the viral structural protein p15 from avian myeloblastosis virus emerges from ion-exchange column chromatography along with a proteolytic activity. p15 is apparently pure, as judged by sodium dodecyl sulfate-polyacryl-amide gel electrophoresis and isoelectric focusing. Increase and decrease in proteolytic activity coincided exactly with increasing and decreasing amounts of p15 during ion-exchange chromatography and during size fractionation by gell filtration. The proteolytic activity cleaved various substrates such as bovine serum albumin, ovalbumin, concanavalin A, and casein after denaturation by sodium dodecyl sulfate and heat. Highest enzyme activity was observed around pH 5.7. As judged from its cleavage pattern and its response to proteolytic inhibitors, the proteolytic activity appears papain-like, and the protease responsible for it may be classified as a thiol protease. If added to immunoprecipitated viral polyprotein precursor Pr76, p15 resulted in cleavage of Pr76,which could be inhibited by antibodies against p15.", "contents": "Biochemical properties of p15-associated protease in an avian RNA tumor virus. It was observed that the viral structural protein p15 from avian myeloblastosis virus emerges from ion-exchange column chromatography along with a proteolytic activity. p15 is apparently pure, as judged by sodium dodecyl sulfate-polyacryl-amide gel electrophoresis and isoelectric focusing. Increase and decrease in proteolytic activity coincided exactly with increasing and decreasing amounts of p15 during ion-exchange chromatography and during size fractionation by gell filtration. The proteolytic activity cleaved various substrates such as bovine serum albumin, ovalbumin, concanavalin A, and casein after denaturation by sodium dodecyl sulfate and heat. Highest enzyme activity was observed around pH 5.7. As judged from its cleavage pattern and its response to proteolytic inhibitors, the proteolytic activity appears papain-like, and the protease responsible for it may be classified as a thiol protease. If added to immunoprecipitated viral polyprotein precursor Pr76, p15 resulted in cleavage of Pr76,which could be inhibited by antibodies against p15."}
{"id": "PMID:212598", "title": "Viral DNA synthesis in cells infected with temperature-sensitive mutants of herpes simplex virus type 1.", "content": "Temperature-sensitive mutants of herpes simplex virus type 1 representing eight DNA-negative complementation groups were grouped into the following three categories based on the viral DNA synthesis patterns after shift-up from the permissive to the nonpermissive temperature and after shift-down from the nonpermissive to the permissive temperature in the presence and absence of inhibitors of RNA and protein synthesis. (i) Viral DNA synthesis was inhibited after shift-up in cells infected with tsB, tsH, and tsJ. After shift-down, tsB- and tsH-infected cells synthesized viral DNA in the absence of de novo RNA and protein synthesis whereas tsJ-infected cells synthesized no viral DNA in the absence of protein synthesis. The B, H, and J proteins appear to be continuously required for the synthesis of viral DNA. (ii) Viral DNA synthesis continued after shift-up in cells infected with tsD and tsK whereas no viral DNA was synthesized after shift-down in the absence of RNA and protein synthesis. Mutants tsD and tsK appear to be defective in early regulatory functions. (iii) Cells infected with tsL, tsS, and tsU synthesized viral DNA after shift-up and after shift-down in the absence of RNA and protein synthesis. The functions of the L, S, and U proteins cannot yet be determined.", "contents": "Viral DNA synthesis in cells infected with temperature-sensitive mutants of herpes simplex virus type 1. Temperature-sensitive mutants of herpes simplex virus type 1 representing eight DNA-negative complementation groups were grouped into the following three categories based on the viral DNA synthesis patterns after shift-up from the permissive to the nonpermissive temperature and after shift-down from the nonpermissive to the permissive temperature in the presence and absence of inhibitors of RNA and protein synthesis. (i) Viral DNA synthesis was inhibited after shift-up in cells infected with tsB, tsH, and tsJ. After shift-down, tsB- and tsH-infected cells synthesized viral DNA in the absence of de novo RNA and protein synthesis whereas tsJ-infected cells synthesized no viral DNA in the absence of protein synthesis. The B, H, and J proteins appear to be continuously required for the synthesis of viral DNA. (ii) Viral DNA synthesis continued after shift-up in cells infected with tsD and tsK whereas no viral DNA was synthesized after shift-down in the absence of RNA and protein synthesis. Mutants tsD and tsK appear to be defective in early regulatory functions. (iii) Cells infected with tsL, tsS, and tsU synthesized viral DNA after shift-up and after shift-down in the absence of RNA and protein synthesis. The functions of the L, S, and U proteins cannot yet be determined."}
{"id": "PMID:212599", "title": "Extraction and fingerprint analysis of simian virus 40 large and small T-antigens.", "content": "A study of simian virus 40 (SV40) T-antigens isolated from productively infected CV1 cells using a variety of different extraction procedures showed that under some conditions the highest molecular weight form of T-Ag (large-T) isolated comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with large-T from SV40-transformed H65-90B cells. Other faster-migrating forms of large-T are probably generated during the extraction procedure by a protease which is active at low pH, and such forms are probably experimental artifacts. After extraction under conditions which minimize proteolytic degradation of large-T, a further form of T-antigen was isolated; this has an apparent molecular weight in the range 15,000 to 20,000 and is referred to as small-t. Fingerprint analysis of [35S]methionine-labeled SV40 proteins showed that small-t has 10 to 12 methionine peptides whereas large-T has 15 to 18 methionine peptides. All but two of the methionine tryptic peptides present in small-t are also present in large-T. The fingerprint data also showed that T-antigens have no peptides in common with SV40 VP1. Experiments using reagents which inhibit posttranslational cleavage of encephalomyocarditis virus polyproteins showed that these reagents do not affect the synthesis of small-t and suggest that it is not made by proteolytic cleavage of large-T in vivo. An alternative model, which proposes that large-T and small-t are synthesized independently, is discussed in terms of the fingerprint data and the number of methionine tryptic peptides predicted from the primary sequence of SV40 DNA.", "contents": "Extraction and fingerprint analysis of simian virus 40 large and small T-antigens. A study of simian virus 40 (SV40) T-antigens isolated from productively infected CV1 cells using a variety of different extraction procedures showed that under some conditions the highest molecular weight form of T-Ag (large-T) isolated comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with large-T from SV40-transformed H65-90B cells. Other faster-migrating forms of large-T are probably generated during the extraction procedure by a protease which is active at low pH, and such forms are probably experimental artifacts. After extraction under conditions which minimize proteolytic degradation of large-T, a further form of T-antigen was isolated; this has an apparent molecular weight in the range 15,000 to 20,000 and is referred to as small-t. Fingerprint analysis of [35S]methionine-labeled SV40 proteins showed that small-t has 10 to 12 methionine peptides whereas large-T has 15 to 18 methionine peptides. All but two of the methionine tryptic peptides present in small-t are also present in large-T. The fingerprint data also showed that T-antigens have no peptides in common with SV40 VP1. Experiments using reagents which inhibit posttranslational cleavage of encephalomyocarditis virus polyproteins showed that these reagents do not affect the synthesis of small-t and suggest that it is not made by proteolytic cleavage of large-T in vivo. An alternative model, which proposes that large-T and small-t are synthesized independently, is discussed in terms of the fingerprint data and the number of methionine tryptic peptides predicted from the primary sequence of SV40 DNA."}
{"id": "PMID:212600", "title": "Cell-free synthesis of simian virus 40 T-antigens.", "content": "Polyacrylamide gel electrophoresis and tryptic peptide fingerprint analysis of the proteins made in a cell-free system derived from L-cells and immunoprecipitated with simian virus 40 (SV40) anti-T serum demonstrated that both SV40 large-T and small-T antigens are synthesized in vitro in response to mRNA isolated from productively infected CV1 CELLS. Sucrose density centrifugation in gradients containing 85% formamide showed that the mRNA's for both forms of T-antigen sediment at about 17.5S, with the mRNA for small-t sedimenting marginally, but reproducibly, ahead of the mRNA for large-T. Hybridization experiments using restriction endonuclease fragments Hae III-E and Hind II/III-B showed that all fractions active in the cell-free synthesis of both forms of T-antigen hybridized equally to both fragments. This suggests that the mRNA's for SV40 T-antigens are at least partly virus coded and that the bulk of the early SV40 mRNA contains sequence information from both ends of the early region. The data are consistent with the suggestion that the large-T mRNA is spliced. SV40 complementary RNA (the product of transcription of SV40 DNA using Escherichia coli RNA polymerase) was also translated in the L-cell system and gave two families of polypeptides which specifically immunoprecipitate with anti-T serum. One family (the small-t family) includes a polypeptide indistinguishable by gel electrophoresis and tryptic peptide fingerprinting from small-t isolated from cells. The other family (the 60K family) has a major component with molecular weight approximately 60,000 and includes other polypeptides with molecular weights ranging from approximately 14,000 to about 70,000. The 60K family has petides in common with large-T but not with small-T. Together, the peptides of the small-t and 60K families account for virtually all of the methionine peptides of SV40 large-T. We conclude from these results (i) that small-t is probably entirely, and large-T at least predominantly, virus coded; (ii) that the small-t and 60K families represent the translation products of two different portions of the early region of SV40 DNA (approximately 0.65 to 0.55 map units and 0.54 to 0.17 map units); and (iii) that although most, if not all, of the large-T and small-t peptides are present in the cell-free product, some feature of sequence arrangement of SV40 complementary RNA prevents the translation of full-length large-T and results instead in the synthesis of fragments. We suggest that the absence of a splice in the complementary RNA is responsible for this result.", "contents": "Cell-free synthesis of simian virus 40 T-antigens. Polyacrylamide gel electrophoresis and tryptic peptide fingerprint analysis of the proteins made in a cell-free system derived from L-cells and immunoprecipitated with simian virus 40 (SV40) anti-T serum demonstrated that both SV40 large-T and small-T antigens are synthesized in vitro in response to mRNA isolated from productively infected CV1 CELLS. Sucrose density centrifugation in gradients containing 85% formamide showed that the mRNA's for both forms of T-antigen sediment at about 17.5S, with the mRNA for small-t sedimenting marginally, but reproducibly, ahead of the mRNA for large-T. Hybridization experiments using restriction endonuclease fragments Hae III-E and Hind II/III-B showed that all fractions active in the cell-free synthesis of both forms of T-antigen hybridized equally to both fragments. This suggests that the mRNA's for SV40 T-antigens are at least partly virus coded and that the bulk of the early SV40 mRNA contains sequence information from both ends of the early region. The data are consistent with the suggestion that the large-T mRNA is spliced. SV40 complementary RNA (the product of transcription of SV40 DNA using Escherichia coli RNA polymerase) was also translated in the L-cell system and gave two families of polypeptides which specifically immunoprecipitate with anti-T serum. One family (the small-t family) includes a polypeptide indistinguishable by gel electrophoresis and tryptic peptide fingerprinting from small-t isolated from cells. The other family (the 60K family) has a major component with molecular weight approximately 60,000 and includes other polypeptides with molecular weights ranging from approximately 14,000 to about 70,000. The 60K family has petides in common with large-T but not with small-T. Together, the peptides of the small-t and 60K families account for virtually all of the methionine peptides of SV40 large-T. We conclude from these results (i) that small-t is probably entirely, and large-T at least predominantly, virus coded; (ii) that the small-t and 60K families represent the translation products of two different portions of the early region of SV40 DNA (approximately 0.65 to 0.55 map units and 0.54 to 0.17 map units); and (iii) that although most, if not all, of the large-T and small-t peptides are present in the cell-free product, some feature of sequence arrangement of SV40 complementary RNA prevents the translation of full-length large-T and results instead in the synthesis of fragments. We suggest that the absence of a splice in the complementary RNA is responsible for this result."}
{"id": "PMID:212601", "title": "Inverted terminal repeats in rabbit poxvirus and vaccinia virus DNA.", "content": "In both rabbit poxvirus and vaccinia virus DNA have demonstrated an identical distribution of eight HinfI. The length of the terminal repeats was found to be 3.4 to 3.6 megadaltons (Mdaltons) for rabbit poxvirus DNA and 7.4 to 8.0 Mdaltons for vaccinia virus DNA. Maps of the HinfI restriction sites within isolated EcoRI end fragments of rabbit poxvirus and vaccinia virus DNA PHAVE DEMONSTRATED AN IDENTICAL DISTRIBUTION OF EIGHT HinfI sites in an internal part (approximately 2 Mdaltons) of the EcoRI end fragments of the two genomes.", "contents": "Inverted terminal repeats in rabbit poxvirus and vaccinia virus DNA. In both rabbit poxvirus and vaccinia virus DNA have demonstrated an identical distribution of eight HinfI. The length of the terminal repeats was found to be 3.4 to 3.6 megadaltons (Mdaltons) for rabbit poxvirus DNA and 7.4 to 8.0 Mdaltons for vaccinia virus DNA. Maps of the HinfI restriction sites within isolated EcoRI end fragments of rabbit poxvirus and vaccinia virus DNA PHAVE DEMONSTRATED AN IDENTICAL DISTRIBUTION OF EIGHT HinfI sites in an internal part (approximately 2 Mdaltons) of the EcoRI end fragments of the two genomes."}
{"id": "PMID:212602", "title": "Physical mapping of herpes simplex virus type 1 mutations by marker rescue.", "content": "A generally applicable technique which permits the rescue of selected genetic markers from fragments of herpes simplex virus DNA is described. Baby hamster kidney cells infected at the nonpermissive temperature with intact DNA from temperature-sensitive mutants or with fragmented wild-type DNA produce no, or little, infectious progeny. Coinfection results in an increased yield of virus, demonstrating the rescue of genetic information from the DNA fragments. This progeny virus consists of both wild-type and temperature-sensitive virus, demonstrating that both recombination and complementation can occur in coinfected cells. Rescue experiments using isolated fragments produced with various restriction endonucleases have enabled us to locate five temperature-sensitive mutations on the herpes simplex virus type 1 physical map. An adaptation of the technique has allowed the physical mapping of a mutation which affects the herpes simplex virus type 1 pyrimidine deoxyribonucleoside kinase gene. Comparison of the genetic and physical maps for these mutants reveals several anomalies which are discussed.", "contents": "Physical mapping of herpes simplex virus type 1 mutations by marker rescue. A generally applicable technique which permits the rescue of selected genetic markers from fragments of herpes simplex virus DNA is described. Baby hamster kidney cells infected at the nonpermissive temperature with intact DNA from temperature-sensitive mutants or with fragmented wild-type DNA produce no, or little, infectious progeny. Coinfection results in an increased yield of virus, demonstrating the rescue of genetic information from the DNA fragments. This progeny virus consists of both wild-type and temperature-sensitive virus, demonstrating that both recombination and complementation can occur in coinfected cells. Rescue experiments using isolated fragments produced with various restriction endonucleases have enabled us to locate five temperature-sensitive mutations on the herpes simplex virus type 1 physical map. An adaptation of the technique has allowed the physical mapping of a mutation which affects the herpes simplex virus type 1 pyrimidine deoxyribonucleoside kinase gene. Comparison of the genetic and physical maps for these mutants reveals several anomalies which are discussed."}
{"id": "PMID:212603", "title": "Replication of nondefective parvoviruses: lack of a virion-associated DNA polymerase.", "content": "We have examined four of the nondefective parvoviruses for an associated DNA polymerase. Virions were purified from neuraminidase-treated infected-cell lysates by isopycnic centrifugation in CsCl or from infected cell material by CaCl(2) precipitation and centrifugation through sucrose into CsCl. Preparations of bovine parvovirus or Kilham rat virus obtained by the former procedure contained DNA polymerase activity but were not free of contaminating cellular proteins. The latter method produced viral preparations free of contaminating cellular proteins, and no DNA polymerase activity was detected in light infectious particles of H-1, LuIII, bovine parvovirus, or Kilham rat virus. Examination of levels of each cellular DNA polymerase in these preparations from each step of both purification procedures revealed that DNA polymerase beta had a greater tendency to copurify with bovine parvovirus and Kilham rat virus than did DNA polymerases alpha or gamma. Disruption of infectious virions obtained by the second purification method with detergents and sonic treatment did not result in the detection of a DNA polymerase activity. The biological activity and purity of each of the four different viruses obtained by the latter procedure were determined by hemagglutination and infectivity assays, polyacrylamide gel electrophoresis, and electron microscopy. In each case, the virions banding at a density of 1.39 to 1.41 g/cm(2) in CsCl were infectious and contained only the virion structural proteins. DNA polymerase activity was not detected in any of these preparations, and we have concluded that a virion-associated DNA polymerase is not required for productive infection with the nondefective parvoviruses.", "contents": "Replication of nondefective parvoviruses: lack of a virion-associated DNA polymerase. We have examined four of the nondefective parvoviruses for an associated DNA polymerase. Virions were purified from neuraminidase-treated infected-cell lysates by isopycnic centrifugation in CsCl or from infected cell material by CaCl(2) precipitation and centrifugation through sucrose into CsCl. Preparations of bovine parvovirus or Kilham rat virus obtained by the former procedure contained DNA polymerase activity but were not free of contaminating cellular proteins. The latter method produced viral preparations free of contaminating cellular proteins, and no DNA polymerase activity was detected in light infectious particles of H-1, LuIII, bovine parvovirus, or Kilham rat virus. Examination of levels of each cellular DNA polymerase in these preparations from each step of both purification procedures revealed that DNA polymerase beta had a greater tendency to copurify with bovine parvovirus and Kilham rat virus than did DNA polymerases alpha or gamma. Disruption of infectious virions obtained by the second purification method with detergents and sonic treatment did not result in the detection of a DNA polymerase activity. The biological activity and purity of each of the four different viruses obtained by the latter procedure were determined by hemagglutination and infectivity assays, polyacrylamide gel electrophoresis, and electron microscopy. In each case, the virions banding at a density of 1.39 to 1.41 g/cm(2) in CsCl were infectious and contained only the virion structural proteins. DNA polymerase activity was not detected in any of these preparations, and we have concluded that a virion-associated DNA polymerase is not required for productive infection with the nondefective parvoviruses."}
{"id": "PMID:212604", "title": "Characterization of the mRNA's for the polyoma virus capsid proteins VP1, VP2, and VP3.", "content": "Polyadenylated cytoplasmic RNA from polyoma virus-infected cells can be translated in the wheat germ system to yield all there polyoma virus capsid proteins, VP1, VP2, and VP3. The translation products of RNA selected from total cytoplasmic RNA of infected cells by hybridization to polyoma virus DNA showed a high degree of enrichment for VP1, VP2, and VP3. The identity of the in vitro products with authentic virion proteins was established in two ways. First, tryptic peptide maps of the in vitro products were found to be essentially identical to those of their in vivo counterparts. Second, the mobilities of the in vitro products on two-dimensional gels were the same as those of viral proteins labeled in vivo. VP1, VP2, and vp3 were all labeled with [35S] formylmethionine when they were synthesized in the presence of [35S] formylmethionyl-tRNAfmet. We determined the sizes of the polyadenylated mRNA's for VP1, VP2, and VP3 by fractionation on gels. The sizes of the major mRNA species for the capsid proteins are as follows: VP2, 8.5 X 10(5) daltons; VP3, 7.4 X 10(5) daltons; and VP1, 4.6 X 10(5) daltons. We conclude that all three viral capsid proteins are synthesized independently in vitro, that all three viral capsid proteins are virally coded, and that each of the capsid proteins has a discrete mRNA.", "contents": "Characterization of the mRNA's for the polyoma virus capsid proteins VP1, VP2, and VP3. Polyadenylated cytoplasmic RNA from polyoma virus-infected cells can be translated in the wheat germ system to yield all there polyoma virus capsid proteins, VP1, VP2, and VP3. The translation products of RNA selected from total cytoplasmic RNA of infected cells by hybridization to polyoma virus DNA showed a high degree of enrichment for VP1, VP2, and VP3. The identity of the in vitro products with authentic virion proteins was established in two ways. First, tryptic peptide maps of the in vitro products were found to be essentially identical to those of their in vivo counterparts. Second, the mobilities of the in vitro products on two-dimensional gels were the same as those of viral proteins labeled in vivo. VP1, VP2, and vp3 were all labeled with [35S] formylmethionine when they were synthesized in the presence of [35S] formylmethionyl-tRNAfmet. We determined the sizes of the polyadenylated mRNA's for VP1, VP2, and VP3 by fractionation on gels. The sizes of the major mRNA species for the capsid proteins are as follows: VP2, 8.5 X 10(5) daltons; VP3, 7.4 X 10(5) daltons; and VP1, 4.6 X 10(5) daltons. We conclude that all three viral capsid proteins are synthesized independently in vitro, that all three viral capsid proteins are virally coded, and that each of the capsid proteins has a discrete mRNA."}
{"id": "PMID:212605", "title": "Synthesis of T4 DNA and bacteriophage in the absence of dCMP hydroxymethylase.", "content": "Several lines of research have suggested that the dCMP hydroxymethylase (HMase) coded by bacteriophage T4 is an essential protein in a DNA replication complex, as well as a supplier of hydroxymethyl dCMP for phage DNA synthesis. We show that a mutant [HMase, dCTPase, endonuclease II, endonuclease IV] which lacked this enzyme made cytosine-containing DNA at about two-thirds of the normal rate. When coupled with an alc mutation which permitted synthesis of late proteins, a small burst of phage was produced whose DNA contained no hydroxymethylcytosine. This pentuple mutant made both early and late proteins with abnormal kinetics, whereas the HMase+ parent showed normal kinetics. However, intracellular phage DNA showed no gross abnormalities in alkaline sucrose gradients. We conclude that HMase is not required for DNA synthesis when hydroxymethyl dCMP is not needed as a substrate; however, its absence still impairs both replication and transcription.", "contents": "Synthesis of T4 DNA and bacteriophage in the absence of dCMP hydroxymethylase. Several lines of research have suggested that the dCMP hydroxymethylase (HMase) coded by bacteriophage T4 is an essential protein in a DNA replication complex, as well as a supplier of hydroxymethyl dCMP for phage DNA synthesis. We show that a mutant [HMase, dCTPase, endonuclease II, endonuclease IV] which lacked this enzyme made cytosine-containing DNA at about two-thirds of the normal rate. When coupled with an alc mutation which permitted synthesis of late proteins, a small burst of phage was produced whose DNA contained no hydroxymethylcytosine. This pentuple mutant made both early and late proteins with abnormal kinetics, whereas the HMase+ parent showed normal kinetics. However, intracellular phage DNA showed no gross abnormalities in alkaline sucrose gradients. We conclude that HMase is not required for DNA synthesis when hydroxymethyl dCMP is not needed as a substrate; however, its absence still impairs both replication and transcription."}
{"id": "PMID:212606", "title": "Heteroduplex analysis of the sequence relations between the RNAs of mink cell focus-inducing and murine leukemia viruses.", "content": "The sequence relationships betwen AKR ecotropic virus and an AKR-derived \"mink cell focus-inducing\" (MCF) isolate (AKR MCF 247), between Moloney murine leukemia virus (M-MLV) and an M-MLV MCF isolate (M-MLV83), and between AKR and M-MLV were studied by electron microscopic heteroduplex analysis. The MCF-specific sequences were found to map from 1.95 kilobases (kb) to 2.75 kb (+/- 0.15 kb) from the 3' end of the RNAs for both MCF isolates. The major sequence nonhomology regions between AKR and M-MLV lie between 0.9 and 3.5 kb from the 3' end. However, the AKR and M-MLV sequences immediately adjacent to the 1.95- and 2.75-kb junctions with MCF-specific sequences are relatively similar in AKR and M-MLV. Our results suggest that the env gene of MLVs maps from 1 kb to 3 kb from the 3' end of the genomic RNA and that the carboxyl end of the glycoprotein of each MCF strain is similar (or identical) to that of its ecotropic parent.", "contents": "Heteroduplex analysis of the sequence relations between the RNAs of mink cell focus-inducing and murine leukemia viruses. The sequence relationships betwen AKR ecotropic virus and an AKR-derived \"mink cell focus-inducing\" (MCF) isolate (AKR MCF 247), between Moloney murine leukemia virus (M-MLV) and an M-MLV MCF isolate (M-MLV83), and between AKR and M-MLV were studied by electron microscopic heteroduplex analysis. The MCF-specific sequences were found to map from 1.95 kilobases (kb) to 2.75 kb (+/- 0.15 kb) from the 3' end of the RNAs for both MCF isolates. The major sequence nonhomology regions between AKR and M-MLV lie between 0.9 and 3.5 kb from the 3' end. However, the AKR and M-MLV sequences immediately adjacent to the 1.95- and 2.75-kb junctions with MCF-specific sequences are relatively similar in AKR and M-MLV. Our results suggest that the env gene of MLVs maps from 1 kb to 3 kb from the 3' end of the genomic RNA and that the carboxyl end of the glycoprotein of each MCF strain is similar (or identical) to that of its ecotropic parent."}
{"id": "PMID:212607", "title": "Biochemical transformation of deoxythymidine kinase-deficient mouse cells with UV-irradiated equine herpesvirus type 1.", "content": "A line of 3T3 mouse cells lacking deoxythymidine kinase (dTK-) was stably transformed to the dTK+ phenotype after exposure to UV-irradiated equine herpesvirus type 1 (EHV-1). Biochemical transformants were isolated in a system selective for the dTK+ phenotype (Eagle minimal essential medium containing 10(-4) M hypoxanthine, 6 X 10(-7) M aminopterin, and 2 X 10(-5) M deoxythymidine). Transformation was accompanied by the acquisition of a dTK activity with immunological, electrophoretic, and biochemical characteristics identical to those of the dTK induced by EHV-1 during productive infection. The transformed cells have been maintained in selective culture medium for more than 50 passages and have retained the capacity to express EHV-1--specific antigens. Spontaneous release of infectious virus has not been detected in the transformed lines, and the the cells were not oncogenic for athymic nude mice. In contrast to normal dTk+ 3T3 cells, EHV-1 transformants were unable to grow in the presence of arabinosylthymine, a drug selectively phosphorylated by herpesvirus-coded dTK's. These results indicate that a portion of the EHV-1 genome is able to persist in the transformed cells for many generations and be expressed as an enzymatically active viral gene product.", "contents": "Biochemical transformation of deoxythymidine kinase-deficient mouse cells with UV-irradiated equine herpesvirus type 1. A line of 3T3 mouse cells lacking deoxythymidine kinase (dTK-) was stably transformed to the dTK+ phenotype after exposure to UV-irradiated equine herpesvirus type 1 (EHV-1). Biochemical transformants were isolated in a system selective for the dTK+ phenotype (Eagle minimal essential medium containing 10(-4) M hypoxanthine, 6 X 10(-7) M aminopterin, and 2 X 10(-5) M deoxythymidine). Transformation was accompanied by the acquisition of a dTK activity with immunological, electrophoretic, and biochemical characteristics identical to those of the dTK induced by EHV-1 during productive infection. The transformed cells have been maintained in selective culture medium for more than 50 passages and have retained the capacity to express EHV-1--specific antigens. Spontaneous release of infectious virus has not been detected in the transformed lines, and the the cells were not oncogenic for athymic nude mice. In contrast to normal dTk+ 3T3 cells, EHV-1 transformants were unable to grow in the presence of arabinosylthymine, a drug selectively phosphorylated by herpesvirus-coded dTK's. These results indicate that a portion of the EHV-1 genome is able to persist in the transformed cells for many generations and be expressed as an enzymatically active viral gene product."}
{"id": "PMID:212608", "title": "Assembly of viral membranes: maturation of the vesicular stomatitis virus glycoprotein in the presence of tunicamycin.", "content": "The role of glycosylation in the maturation of the vesicular stomatitis virus (VSV) glycoprotein was studied by use of the antibiotic tunicamycin. Tunicamycin-treated VSV-infected cells synthesize an unglycosylated form of the VSV glycoprotein (R. Leavitt, S. Schlesinger, and S. Kornfeld, J. Virol. 21:375--385, 1977). We have found that tunicamycin has no effect on the attachment of the glycoprotein to intracellular membranes or on the transport of protein to the lumen of the endoplasmic reticulum. However, tunicamycin prevented the migration of the glycoprotein from the rough endoplasmic reticulum to smooth intracellular membranes.", "contents": "Assembly of viral membranes: maturation of the vesicular stomatitis virus glycoprotein in the presence of tunicamycin. The role of glycosylation in the maturation of the vesicular stomatitis virus (VSV) glycoprotein was studied by use of the antibiotic tunicamycin. Tunicamycin-treated VSV-infected cells synthesize an unglycosylated form of the VSV glycoprotein (R. Leavitt, S. Schlesinger, and S. Kornfeld, J. Virol. 21:375--385, 1977). We have found that tunicamycin has no effect on the attachment of the glycoprotein to intracellular membranes or on the transport of protein to the lumen of the endoplasmic reticulum. However, tunicamycin prevented the migration of the glycoprotein from the rough endoplasmic reticulum to smooth intracellular membranes."}
{"id": "PMID:212609", "title": "Two initiation sites for translation of poliovirus RNA in vitro: comparison of LSc and Mahoney strains.", "content": "Previous studies in our laboratory provided evidence that the initiation of translation by the Mahoney strain of poliovirus type 1 RNA in vitro occurs at two unique sites. This study shows that the LSc strain of poliovirus type 1, a multistep, temperature-sensitive mutant of the Mahoney strain, also utilizes two sites for the initiation of translation in vitro. Incorporation of formyl-[35S]methionine into the amino terminus of newly synthesized polypeptides revealed the production of two labeled tryptic peptides which are identical in size and electrophoretic mobility with those produced by Mahoney virus. The polypeptides containing amino-terminal label showed similar patterns on sodium dodecyl sulfate-acrylamide gels, although one of the LSc polypeptides had a slightly faster mobility. The relative proportion of initiation at each site varied with the magnesium concentration for both viruses, but the LSc strain favored initiation at one site more so than did the Mahoney strain.", "contents": "Two initiation sites for translation of poliovirus RNA in vitro: comparison of LSc and Mahoney strains. Previous studies in our laboratory provided evidence that the initiation of translation by the Mahoney strain of poliovirus type 1 RNA in vitro occurs at two unique sites. This study shows that the LSc strain of poliovirus type 1, a multistep, temperature-sensitive mutant of the Mahoney strain, also utilizes two sites for the initiation of translation in vitro. Incorporation of formyl-[35S]methionine into the amino terminus of newly synthesized polypeptides revealed the production of two labeled tryptic peptides which are identical in size and electrophoretic mobility with those produced by Mahoney virus. The polypeptides containing amino-terminal label showed similar patterns on sodium dodecyl sulfate-acrylamide gels, although one of the LSc polypeptides had a slightly faster mobility. The relative proportion of initiation at each site varied with the magnesium concentration for both viruses, but the LSc strain favored initiation at one site more so than did the Mahoney strain."}
{"id": "PMID:212610", "title": "Identification of Sendai virus mRNA species.", "content": "Cell-free translation of separated Sendai virus mRNA species identified the message for polypeptide M and suggested the identity of the message for polypeptide NP.", "contents": "Identification of Sendai virus mRNA species. Cell-free translation of separated Sendai virus mRNA species identified the message for polypeptide M and suggested the identity of the message for polypeptide NP."}
{"id": "PMID:212611", "title": "Simian virus 40 production after viral uncoating in the CV-1 cell nucleus.", "content": "A normal yield of infectious simian virus 40 was produced by a CV-1 cell culture after inoculation of a few cells with an average of one particle per nucleus by microinjection.", "contents": "Simian virus 40 production after viral uncoating in the CV-1 cell nucleus. A normal yield of infectious simian virus 40 was produced by a CV-1 cell culture after inoculation of a few cells with an average of one particle per nucleus by microinjection."}
{"id": "PMID:212612", "title": "Mechanism of transfection of chicken embryo fibroblasts by Rous sarcoma virus DNA.", "content": "The mechanism of transfection by Rous sarcoma virus DNA was investigated by assaying DNA-mediated transformation under conditions which restricted secondary virus infection. Chicken embryo fibroblasts which were genetically resistant to virus infection as a result of the absence of receptors for virus penetration were also resistant to transformation by integrated or unintegrated Rous sarcoma virus DNA. In addition, DNA of replication-defective Bryan hightiter Rous sarcoma virus was noninfectious, and transformation by DNA of a temperature-sensitive DNA polymerase mutant was temperature sensitive. These results indicated that secondary virus infection was necessary for transformation by Rous sarcoma virus DNA. Since transformation was assayed by colony formation in soft agar, as well as by focus formation, the requirement for secondary virus infection was not an artifact of potential difficulty in detection of foci formed by division of single transformed cells. Therefore, it appeared that donor DNA did not stably transform recipient cells by direct integration. Instead, the results were consistent with the hypothesis that transfection of chicken embryo fibroblasts by Rous sarcoma virus DNA proceeded by transcription of donor DNA, formation of extracellular progeny virus, and secondary virus infection of sensitive cells.", "contents": "Mechanism of transfection of chicken embryo fibroblasts by Rous sarcoma virus DNA. The mechanism of transfection by Rous sarcoma virus DNA was investigated by assaying DNA-mediated transformation under conditions which restricted secondary virus infection. Chicken embryo fibroblasts which were genetically resistant to virus infection as a result of the absence of receptors for virus penetration were also resistant to transformation by integrated or unintegrated Rous sarcoma virus DNA. In addition, DNA of replication-defective Bryan hightiter Rous sarcoma virus was noninfectious, and transformation by DNA of a temperature-sensitive DNA polymerase mutant was temperature sensitive. These results indicated that secondary virus infection was necessary for transformation by Rous sarcoma virus DNA. Since transformation was assayed by colony formation in soft agar, as well as by focus formation, the requirement for secondary virus infection was not an artifact of potential difficulty in detection of foci formed by division of single transformed cells. Therefore, it appeared that donor DNA did not stably transform recipient cells by direct integration. Instead, the results were consistent with the hypothesis that transfection of chicken embryo fibroblasts by Rous sarcoma virus DNA proceeded by transcription of donor DNA, formation of extracellular progeny virus, and secondary virus infection of sensitive cells."}
{"id": "PMID:212613", "title": "Simian virus 40 DNA replication in isolated replicating viral chromosomes.", "content": "Three subnuclear systems capable of continuing many aspects of simian virus 40 (SV40) DNA replication were characterized in an effort to define the minimum requirements for \"normal\" DNA replication in vitro. Nuclear extracts, prepared by incubating nuclei isolated from SV40-infected CV-1 cells in a hypotonic buffer to release both SV40 replicating and mature chromosomes, were either centrifuged to separate the total SV40 nucleoprotein complexes from the soluble nucleosol or fractionated on sucrose gradients to provide purified SV40 replicating chromosomes. With nuclear extracts, CV-1 cell cytosol stimulated total DNA synthesis, elongation of nascent DNA chains, maturation and joining of \"Okazaki pieces,\" and the conversion of replicating viral DNA into covalently closed, superhelical DNA. Nucleoprotein complexes responded similarly, but frequently the response was reduced by 10 to 30%. In contrast, isolated replicating chromosomes in the presence of cytosol appeared only to complete and join Okazaki pieces already present on the template; without cytosol, Okazaki pieces incorporated alpha-(32)P-labeled deoxynucleoside triphosphates but failed to join. Consequently, replicating chromosomes failed to extensively continue nascent DNA chain growth, and the conversion of viral replicating DNA into mature DNA was seven to eight times less than that observed in nuclear extracts. Addition of neither cytosol nor nucleosol corrected this problem. In the presence of cytosol, nonspecific endonuclease activity was not a problem in any of the three in vitro systems. Extensive purification of replicating chromosomes was limited by three as yet irreversible phenomena. First, replicating chromosomes isolated in a low-ionic-strength medium had a limited capability to continue DNA synthesis. Second, diluting either nuclear extracts or replicating chromosomes before incubation in vitro stimulated total DNA synthesis but was accompanied by the simultaneous appearance of small-molecular-weight nascent DNA not associated with intact viral DNA templates and a decrease in the synthesis of covalently closed viral DNA. Although this second phenomenon appeared similar to the first, template concentration alone could not account for the failure of purified replicating chromosomes to yield covalently closed DNA. Finally, preparation of nucleoprotein complexes in increasing concentrations of NaCl progressively decreased their ability to continue DNA replication. Exposure to 0.3 M NaCl removed one or more factors required for DNA synthesis which could be replaced by addition of cytosol. However, higher NaCl concentrations yielded nucleoprotein complexes that had relatively no endogenous DNA synthesis activity and that no longer responded to cytosol. These data demonstrate that continuation of endogenous DNA replication in vitro requires both the soluble cytosol fraction and a complex nucleoprotein template whose ability to continue DNA synthesis depends on its concentration and ionic environment during its preparation.", "contents": "Simian virus 40 DNA replication in isolated replicating viral chromosomes. Three subnuclear systems capable of continuing many aspects of simian virus 40 (SV40) DNA replication were characterized in an effort to define the minimum requirements for \"normal\" DNA replication in vitro. Nuclear extracts, prepared by incubating nuclei isolated from SV40-infected CV-1 cells in a hypotonic buffer to release both SV40 replicating and mature chromosomes, were either centrifuged to separate the total SV40 nucleoprotein complexes from the soluble nucleosol or fractionated on sucrose gradients to provide purified SV40 replicating chromosomes. With nuclear extracts, CV-1 cell cytosol stimulated total DNA synthesis, elongation of nascent DNA chains, maturation and joining of \"Okazaki pieces,\" and the conversion of replicating viral DNA into covalently closed, superhelical DNA. Nucleoprotein complexes responded similarly, but frequently the response was reduced by 10 to 30%. In contrast, isolated replicating chromosomes in the presence of cytosol appeared only to complete and join Okazaki pieces already present on the template; without cytosol, Okazaki pieces incorporated alpha-(32)P-labeled deoxynucleoside triphosphates but failed to join. Consequently, replicating chromosomes failed to extensively continue nascent DNA chain growth, and the conversion of viral replicating DNA into mature DNA was seven to eight times less than that observed in nuclear extracts. Addition of neither cytosol nor nucleosol corrected this problem. In the presence of cytosol, nonspecific endonuclease activity was not a problem in any of the three in vitro systems. Extensive purification of replicating chromosomes was limited by three as yet irreversible phenomena. First, replicating chromosomes isolated in a low-ionic-strength medium had a limited capability to continue DNA synthesis. Second, diluting either nuclear extracts or replicating chromosomes before incubation in vitro stimulated total DNA synthesis but was accompanied by the simultaneous appearance of small-molecular-weight nascent DNA not associated with intact viral DNA templates and a decrease in the synthesis of covalently closed viral DNA. Although this second phenomenon appeared similar to the first, template concentration alone could not account for the failure of purified replicating chromosomes to yield covalently closed DNA. Finally, preparation of nucleoprotein complexes in increasing concentrations of NaCl progressively decreased their ability to continue DNA replication. Exposure to 0.3 M NaCl removed one or more factors required for DNA synthesis which could be replaced by addition of cytosol. However, higher NaCl concentrations yielded nucleoprotein complexes that had relatively no endogenous DNA synthesis activity and that no longer responded to cytosol. These data demonstrate that continuation of endogenous DNA replication in vitro requires both the soluble cytosol fraction and a complex nucleoprotein template whose ability to continue DNA synthesis depends on its concentration and ionic environment during its preparation."}
{"id": "PMID:212614", "title": "Persistent infection of L cells with vesicular stomatitis virus: evolution of virus populations.", "content": "A previous report (Youngner et al., J. Virol. 19:90-101, 1976) documented that noncytocidal persistent infection can be established with wild-type vesicular stomatitis virus (VSV) in mouse L cells at 37 degrees C and that a rapid selection of RNA(-), group I temperature-sensitive (ts) mutants consistently occurs in this system. To assess the selective advantage of the RNA(-)ts phenotype, evolution of the virus population was studied in persistent infections initiated in L cells by use of VSV ts 0 23 and ts 0 45, RNA(+) mutants belonging to complementation groups III and V. In L cells persistently infected with ts 0 23, the ts RNA(+) virus population was replaced gradually by viruses which had a ts RNA(-) phenotype. VSV ts 0 45 (V) has another marker in addition to reduced virus yield at 39.5 degrees C: a defective protein (G) which renders virion infectivity heat labile at 50 degrees C. Persistent infections initiated with this virus (ts, heat labile, RNA(+)) evolved into a virus population which was ts, heat resistant, and RNA(-). These findings suggest that the ts phenotype itself is not sufficient to stabilize the VSV population in persistently infected L cells and also indicate that the ts RNA(-) phenotype may have a unique selective advantage in this system. In addition to the selection of ts RNA(-) mutants, other mechanisms which also might operate in the maintenance of persistent VSV infections of L cells were explored. Whereas defective-interfering particles did not seem to mediate the carrier state, evidence was obtained that interferon may play a role in the regulation of persistent infections of L cells with VSV.", "contents": "Persistent infection of L cells with vesicular stomatitis virus: evolution of virus populations. A previous report (Youngner et al., J. Virol. 19:90-101, 1976) documented that noncytocidal persistent infection can be established with wild-type vesicular stomatitis virus (VSV) in mouse L cells at 37 degrees C and that a rapid selection of RNA(-), group I temperature-sensitive (ts) mutants consistently occurs in this system. To assess the selective advantage of the RNA(-)ts phenotype, evolution of the virus population was studied in persistent infections initiated in L cells by use of VSV ts 0 23 and ts 0 45, RNA(+) mutants belonging to complementation groups III and V. In L cells persistently infected with ts 0 23, the ts RNA(+) virus population was replaced gradually by viruses which had a ts RNA(-) phenotype. VSV ts 0 45 (V) has another marker in addition to reduced virus yield at 39.5 degrees C: a defective protein (G) which renders virion infectivity heat labile at 50 degrees C. Persistent infections initiated with this virus (ts, heat labile, RNA(+)) evolved into a virus population which was ts, heat resistant, and RNA(-). These findings suggest that the ts phenotype itself is not sufficient to stabilize the VSV population in persistently infected L cells and also indicate that the ts RNA(-) phenotype may have a unique selective advantage in this system. In addition to the selection of ts RNA(-) mutants, other mechanisms which also might operate in the maintenance of persistent VSV infections of L cells were explored. Whereas defective-interfering particles did not seem to mediate the carrier state, evidence was obtained that interferon may play a role in the regulation of persistent infections of L cells with VSV."}
{"id": "PMID:212615", "title": "Nucleotide sequence relationship between intracisternal type A particles of Mus musculus and an endogenous retrovirus (M432) of Mus cervicolor.", "content": "Intracisternal type A particles are retrovirus-like structures found in embryonic cells and many tumors of Mus musculus but having no clear relationship with other retroviruses of this mouse species. We have observed a partial nucleotide sequence homology between the high-molecular-weight (32S and 35S) RNA components of intracisternal A-particles from a neuroblastoma cell line and the 70S RNA fraction from M432, a type of retrovirus endogenous to the Asian mouse Mus cervicolor. M432 complementary DNA (cDNA) was hybridized to the extent of 30% by the A-particle RNAs. The hybrids showed a lower thermal stability (DeltaT(m), 7 degrees C) than those formed with homologous RNA. The reaction was commensurate with that found between M432 cDNA and divergent sequences in the M. musculus genome. The capacity to hybridize M432 cDNA was closely correlated with the concentration of A-particle sequences in the cytoplasmic RNA of several M. musculus cell types. The major RNA fraction of M432 virus showed a reciprocal partial reaction with the A-particle cDNA's; the virus, which was grown in NIH/3T3 (M. musculus) cells, also contained a small proportion of apparently authentic A-particle nucleotide sequences. A subset of A-particle sequences seemed to be almost totally lacking in the main M432 RNA. The A-particle cDNA's hybridized extensively with divergent sequences in M. cervicolor cellular DNA, indicating that this mouse species may contain not only the partially homologous M432 virogene, but also a more complete genetic equivalent of the intracisternal A-particle.", "contents": "Nucleotide sequence relationship between intracisternal type A particles of Mus musculus and an endogenous retrovirus (M432) of Mus cervicolor. Intracisternal type A particles are retrovirus-like structures found in embryonic cells and many tumors of Mus musculus but having no clear relationship with other retroviruses of this mouse species. We have observed a partial nucleotide sequence homology between the high-molecular-weight (32S and 35S) RNA components of intracisternal A-particles from a neuroblastoma cell line and the 70S RNA fraction from M432, a type of retrovirus endogenous to the Asian mouse Mus cervicolor. M432 complementary DNA (cDNA) was hybridized to the extent of 30% by the A-particle RNAs. The hybrids showed a lower thermal stability (DeltaT(m), 7 degrees C) than those formed with homologous RNA. The reaction was commensurate with that found between M432 cDNA and divergent sequences in the M. musculus genome. The capacity to hybridize M432 cDNA was closely correlated with the concentration of A-particle sequences in the cytoplasmic RNA of several M. musculus cell types. The major RNA fraction of M432 virus showed a reciprocal partial reaction with the A-particle cDNA's; the virus, which was grown in NIH/3T3 (M. musculus) cells, also contained a small proportion of apparently authentic A-particle nucleotide sequences. A subset of A-particle sequences seemed to be almost totally lacking in the main M432 RNA. The A-particle cDNA's hybridized extensively with divergent sequences in M. cervicolor cellular DNA, indicating that this mouse species may contain not only the partially homologous M432 virogene, but also a more complete genetic equivalent of the intracisternal A-particle."}
{"id": "PMID:212618", "title": "Pathogenesis of essential hypertension with low renin: responses of plasma renin activity to various stimulation tests in essential hypertension.", "content": "Plasma renin activity (PRA) was measured in 14 control subjects and 27 patients with essential hypertension (EH) (low renin group: 9, normal renin group: 11, and high renin group: 7) before and after the following stimulation tests. Test procedures: 1) Circadian rhythm (0600, 1600 and 2400h). 2) Adrenal stimulation test (ACTH: 12.5 I.U.). 3) Adrenal suppression test (Dexamethasone: 1.0 mg). 4) Metopirone test (1.5 g). 5) Angiotensin II infusion test (8 ng/kg/min). 6) Saline infusion test (1000 ml/hr). Patients with low PRA showed significantly lower levels of PRA than those of other two groups in circadian rhythm, after 2 hours of ACTH infusion and after angiotensin II infusion. Furthermore, these patients showed significantly higher responses of PRA than other two groups after furosemide test under dexamethasone and after metopirone test. In case of saline infusion test, patients with low and normal PRA did not show significantly decreased levels of PRA after the infusion, though all patients with high PRA and all control subjects showed significantly decreased levels of PRA. From the present studies, it might be concluded that patients with low PRA has an unknown mineralocorticoid excess which is ACTH dependent and 11 hydroxylated and some of hypertensive patients have an abnormality in their renin-angiotensin-aldosterone volume feed back loop as a factor for hypertension.", "contents": "Pathogenesis of essential hypertension with low renin: responses of plasma renin activity to various stimulation tests in essential hypertension. Plasma renin activity (PRA) was measured in 14 control subjects and 27 patients with essential hypertension (EH) (low renin group: 9, normal renin group: 11, and high renin group: 7) before and after the following stimulation tests. Test procedures: 1) Circadian rhythm (0600, 1600 and 2400h). 2) Adrenal stimulation test (ACTH: 12.5 I.U.). 3) Adrenal suppression test (Dexamethasone: 1.0 mg). 4) Metopirone test (1.5 g). 5) Angiotensin II infusion test (8 ng/kg/min). 6) Saline infusion test (1000 ml/hr). Patients with low PRA showed significantly lower levels of PRA than those of other two groups in circadian rhythm, after 2 hours of ACTH infusion and after angiotensin II infusion. Furthermore, these patients showed significantly higher responses of PRA than other two groups after furosemide test under dexamethasone and after metopirone test. In case of saline infusion test, patients with low and normal PRA did not show significantly decreased levels of PRA after the infusion, though all patients with high PRA and all control subjects showed significantly decreased levels of PRA. From the present studies, it might be concluded that patients with low PRA has an unknown mineralocorticoid excess which is ACTH dependent and 11 hydroxylated and some of hypertensive patients have an abnormality in their renin-angiotensin-aldosterone volume feed back loop as a factor for hypertension."}
{"id": "PMID:212619", "title": "Hypertension induced by adrenocortical dysfunction--hypertension in 17 alpha-hydroxylase deficiency and metopirone-induced hypertension.", "content": "Hypertension in 17 alpha-hydroxylase deficiency was studied by comparing it with hypertension in Cushing syndrome or that in primary aldosteronism. Furthermore, the role of endogenous increases of ACTH, deoxycorticosterone, and 18 alpha-hydroxy-deoxycorticosterone upon blood pressure was studied in rats  by administerating metopirone. Hypertension in 17 alpha-hydroxylase deficiency was considered to be more similar to that in primary aldosteronism from the studies on renin components, pressor responses to angiotensin II and norepinephrine, and renin responses to stimulations. Plasma catecholamines were slightly decreased in 17 alpha-hydroxylase deficiency. The hypertension was alleviated by the administeration of dexamethasone in 2 of 3 patients with 17 alpha-hydroxylase deficiency. However, in the remaining one who had an accelerated hypertension and normal renin, the hypertension was not alleviated by dexamethasone. In the animal studies, hypertension induced by metopirone was accelerated by salt loading of uni-lateral nephrectomy plus salt loading. In those rats, plasma ACTH, and deoxycorticosterone were markedly increased.", "contents": "Hypertension induced by adrenocortical dysfunction--hypertension in 17 alpha-hydroxylase deficiency and metopirone-induced hypertension. Hypertension in 17 alpha-hydroxylase deficiency was studied by comparing it with hypertension in Cushing syndrome or that in primary aldosteronism. Furthermore, the role of endogenous increases of ACTH, deoxycorticosterone, and 18 alpha-hydroxy-deoxycorticosterone upon blood pressure was studied in rats  by administerating metopirone. Hypertension in 17 alpha-hydroxylase deficiency was considered to be more similar to that in primary aldosteronism from the studies on renin components, pressor responses to angiotensin II and norepinephrine, and renin responses to stimulations. Plasma catecholamines were slightly decreased in 17 alpha-hydroxylase deficiency. The hypertension was alleviated by the administeration of dexamethasone in 2 of 3 patients with 17 alpha-hydroxylase deficiency. However, in the remaining one who had an accelerated hypertension and normal renin, the hypertension was not alleviated by dexamethasone. In the animal studies, hypertension induced by metopirone was accelerated by salt loading of uni-lateral nephrectomy plus salt loading. In those rats, plasma ACTH, and deoxycorticosterone were markedly increased."}
{"id": "PMID:212625", "title": "Effect of sodium ion on levels of cyclic adenosine 3',5'-monophosphate in guinea pig cerebral slices.", "content": "Accumulation of cyclic AMP was studied in guinea pig cerebral slices when Na+ levels in the bathing medium were varied or agents which affect tissue Na+ content were added. When NaCl was gradually replaced with Tris-HCl or choline chloride, cyclic AMP formation was progressively enhanced. ;when Na+ was below 30 mM,  cyclic AMP formation reached the maximum (approximately 30 fold), but this increment was not blocked by tetrodotoxin. The stimulatory effect of high K+ was nearly linear over 120 mM and became much more prominent when Na+ also was not blocked by tetrodotoxin. Ouabain (10(-4) M), electrical pulses and glutamate (5 x 10(-3) M), each stimulated cyclic AMP formation about 17-, 7- and 5-fold, respectively. Tetrodotoxin (2 x 10(-6) M) completely blocked the effects of electrical pulses and partially blocked the effects of glutamate and oubain. It is suggested that the increase of cyclic AMP in cerebral cortical slices may be related to the decrease in Na+ gradient across the cell membrane.", "contents": "Effect of sodium ion on levels of cyclic adenosine 3',5'-monophosphate in guinea pig cerebral slices. Accumulation of cyclic AMP was studied in guinea pig cerebral slices when Na+ levels in the bathing medium were varied or agents which affect tissue Na+ content were added. When NaCl was gradually replaced with Tris-HCl or choline chloride, cyclic AMP formation was progressively enhanced. ;when Na+ was below 30 mM,  cyclic AMP formation reached the maximum (approximately 30 fold), but this increment was not blocked by tetrodotoxin. The stimulatory effect of high K+ was nearly linear over 120 mM and became much more prominent when Na+ also was not blocked by tetrodotoxin. Ouabain (10(-4) M), electrical pulses and glutamate (5 x 10(-3) M), each stimulated cyclic AMP formation about 17-, 7- and 5-fold, respectively. Tetrodotoxin (2 x 10(-6) M) completely blocked the effects of electrical pulses and partially blocked the effects of glutamate and oubain. It is suggested that the increase of cyclic AMP in cerebral cortical slices may be related to the decrease in Na+ gradient across the cell membrane."}
{"id": "PMID:212634", "title": "[Mechanism of the change in adipocyte sensitivity to ACTH and adrenaline in spontaneous genetic hypertesion in rats].", "content": "As compared to fatty tissue cells of animals with normal pressure, those of SHR rats were found to be characterized by a higher lipolytic response and a larger increase in the cAMP content on exposure to the effect of ACTH. As compared to the controls, adrenalectomized SHR rats had an increased basal cAMP content and an increased lipolytic response of the adipocytes following adrenaline administration. In inhibition of phosphodiesterase in the fatty cells of adrenalectomized rats with normal pressure, the cAMP content grew by 20% as compared to that in SHR rats subjected to the operation. It is suggested that the changes in intracellular distribution of calcium, shown in this model of hypertension, may be the direct cause of the altered sensitivity of the \"target\" cells to the effect of hormones.", "contents": "[Mechanism of the change in adipocyte sensitivity to ACTH and adrenaline in spontaneous genetic hypertesion in rats]. As compared to fatty tissue cells of animals with normal pressure, those of SHR rats were found to be characterized by a higher lipolytic response and a larger increase in the cAMP content on exposure to the effect of ACTH. As compared to the controls, adrenalectomized SHR rats had an increased basal cAMP content and an increased lipolytic response of the adipocytes following adrenaline administration. In inhibition of phosphodiesterase in the fatty cells of adrenalectomized rats with normal pressure, the cAMP content grew by 20% as compared to that in SHR rats subjected to the operation. It is suggested that the changes in intracellular distribution of calcium, shown in this model of hypertension, may be the direct cause of the altered sensitivity of the \"target\" cells to the effect of hormones."}
{"id": "PMID:212638", "title": "[Myoclonic-astatic seizures (Lennox syndrome) in the course of juvenile neuronal ceroid-lipofuscinosis (M. Batten-Spielmeyer-Vogt) (author's transl)].", "content": "EEG findings and the course of epileptic seizures in two patients with neuronal ceroid lipofuscinosis (Batten Spielmeyer Vogt syndrome) are presented. Both patients, during the course of disease, developed therapy resistant epileptic reactions with myoclonicastatic seizures. These seizures in connection with diffuse encephalopathy and EEG pattern with 2.5 to 3.5/sec slow-spike-wave meet the criteria of the Lennox syndrome. Pathogenetic questions regarding possible additional genetic predisposition for epileptic seizures are discussed. Since therapeutic effect of different medications is uncertain hormonal therapy may be considered.", "contents": "[Myoclonic-astatic seizures (Lennox syndrome) in the course of juvenile neuronal ceroid-lipofuscinosis (M. Batten-Spielmeyer-Vogt) (author's transl)]. EEG findings and the course of epileptic seizures in two patients with neuronal ceroid lipofuscinosis (Batten Spielmeyer Vogt syndrome) are presented. Both patients, during the course of disease, developed therapy resistant epileptic reactions with myoclonicastatic seizures. These seizures in connection with diffuse encephalopathy and EEG pattern with 2.5 to 3.5/sec slow-spike-wave meet the criteria of the Lennox syndrome. Pathogenetic questions regarding possible additional genetic predisposition for epileptic seizures are discussed. Since therapeutic effect of different medications is uncertain hormonal therapy may be considered."}
{"id": "PMID:212639", "title": "Metabolic bone disease resembling osteosarcoma in a wooly monkey (Lagothrix lagotricha).", "content": "A female pet wooly monkey with metabolic bone disease initially presented with a proliferating bony mass in the left humerus which had many features of osteosarcoma. At necropsy, parathyroid hyperplasia, osteoclastic resorption, proliferative osteoid deposition in the calvarium and cortex of long bones, and fibrous proliferation of the marrow indicated the presence of generalized osteodystrophia fibrosa. The dietary history of deficient vitamin D3 and protein and minimal exposure to sunlight supported this diagnosis, as did depressed levels of serum calcium and elevated levels of serum parathyroid hormone, alkaline phosphatase, and acid phosphatase.", "contents": "Metabolic bone disease resembling osteosarcoma in a wooly monkey (Lagothrix lagotricha). A female pet wooly monkey with metabolic bone disease initially presented with a proliferating bony mass in the left humerus which had many features of osteosarcoma. At necropsy, parathyroid hyperplasia, osteoclastic resorption, proliferative osteoid deposition in the calvarium and cortex of long bones, and fibrous proliferation of the marrow indicated the presence of generalized osteodystrophia fibrosa. The dietary history of deficient vitamin D3 and protein and minimal exposure to sunlight supported this diagnosis, as did depressed levels of serum calcium and elevated levels of serum parathyroid hormone, alkaline phosphatase, and acid phosphatase."}
{"id": "PMID:212640", "title": "Disseminated lymphoma in a rhesus monkey: a case report.", "content": "A rhesus monkey was inoculated with rhesus cytomegalovirus. A leukocyte-associated herpes virus, unrelated to cytomegalovirus, was later isolated from the same monkey. Four years after the virus inoculation, the monkey developed a disseminated lymphoma.", "contents": "Disseminated lymphoma in a rhesus monkey: a case report. A rhesus monkey was inoculated with rhesus cytomegalovirus. A leukocyte-associated herpes virus, unrelated to cytomegalovirus, was later isolated from the same monkey. Four years after the virus inoculation, the monkey developed a disseminated lymphoma."}
{"id": "PMID:212641", "title": "Composition of bronchoalveolar lavage effluents from patients with pulmonary alveolar proteinosis.", "content": "The lungs of patients with pulmonary alveolar proteinosis were lavaged with saline. The lavage effluents were examined for the presence of unusual components which might be considered characteristic of the disease. Soluble proteins were resolved by electrophoresis on polyacrylamide linear gradient (2.5 to 27 per cent acrylamide) gel slabs and compared with proteins found in the patients' sera and lavage effluents from nondiseased human lungs. Many proteins in lavage effluents from both diseased and nondiseased lungs appeared similar to those found in serum. Several proteins from diseased lungs were not present in serum nor lavage effluents from nondiseased lungs. A number of proteins present in lavage effluents from nondiseased lungs appeared to be absent from lungs with alveolar proteinosis. Particulate components of lavage effluents from diseased and normal lungs were examined and compared using the electron microscope. Many particulate components including degenerate and disintegrating cells, ultrastructurally abnormal alveolar macrophages, and myelin-like structures were present in lavage effluents from diseased lungs but absent from normal lungs. Much of the particulate material resembled cell debris. The insoluble accumulations present in the pulmonary alveoli and airways of patients with alveolar proteinosis do not come from serum leakage nor from hypersecretion of materials normally found in these regions of the lungs. The major insoluble components appear to arise from cellular disintegration and the extracellular formation of myelin-like structures.", "contents": "Composition of bronchoalveolar lavage effluents from patients with pulmonary alveolar proteinosis. The lungs of patients with pulmonary alveolar proteinosis were lavaged with saline. The lavage effluents were examined for the presence of unusual components which might be considered characteristic of the disease. Soluble proteins were resolved by electrophoresis on polyacrylamide linear gradient (2.5 to 27 per cent acrylamide) gel slabs and compared with proteins found in the patients' sera and lavage effluents from nondiseased human lungs. Many proteins in lavage effluents from both diseased and nondiseased lungs appeared similar to those found in serum. Several proteins from diseased lungs were not present in serum nor lavage effluents from nondiseased lungs. A number of proteins present in lavage effluents from nondiseased lungs appeared to be absent from lungs with alveolar proteinosis. Particulate components of lavage effluents from diseased and normal lungs were examined and compared using the electron microscope. Many particulate components including degenerate and disintegrating cells, ultrastructurally abnormal alveolar macrophages, and myelin-like structures were present in lavage effluents from diseased lungs but absent from normal lungs. Much of the particulate material resembled cell debris. The insoluble accumulations present in the pulmonary alveoli and airways of patients with alveolar proteinosis do not come from serum leakage nor from hypersecretion of materials normally found in these regions of the lungs. The major insoluble components appear to arise from cellular disintegration and the extracellular formation of myelin-like structures."}
{"id": "PMID:212642", "title": "Complications of leprosy.", "content": "Leprosy is essentially a systemic disease and is a great \"mimicker\" of many other diseases. It affects apart from skin and peripheral nerves, haemopoietic, reticulo-endothelial and endocrine systems as well as eyes, bones and muscles.", "contents": "Complications of leprosy. Leprosy is essentially a systemic disease and is a great \"mimicker\" of many other diseases. It affects apart from skin and peripheral nerves, haemopoietic, reticulo-endothelial and endocrine systems as well as eyes, bones and muscles."}
{"id": "PMID:212646", "title": "Sleep during chronic ethanol administration and withdrawal in rats.", "content": "After a priming dose, ethanol was administered at a rate relative to behavioral impairment for 4 days and its effects on sleep were monitored by EEG. EEG's during withdrawal indicated an initial sleep loss followed by a return of total sleep and a REM sleep rebound several days later.", "contents": "Sleep during chronic ethanol administration and withdrawal in rats. After a priming dose, ethanol was administered at a rate relative to behavioral impairment for 4 days and its effects on sleep were monitored by EEG. EEG's during withdrawal indicated an initial sleep loss followed by a return of total sleep and a REM sleep rebound several days later."}
{"id": "PMID:212647", "title": "Granular cell myoblastoma of the bronchus. Case report and literature review.", "content": "A case of multiple granular cell myoblastomas of the tracheobronchial tree is presented. The patient is well 32 months following endobronchial removal. Only 46 cases of solitary and two cases of multiple lesions of the tracheobronchial tree have been described in the literature. These lesions occur with equal frequency in men and women; at a median age of 38 years; more frequently on the right than on the left; and most commonly with cough as the presenting symptom. Most patients have been treated with major surgical resections, but conservative endobronchial removal may be effective therapy.", "contents": "Granular cell myoblastoma of the bronchus. Case report and literature review. A case of multiple granular cell myoblastomas of the tracheobronchial tree is presented. The patient is well 32 months following endobronchial removal. Only 46 cases of solitary and two cases of multiple lesions of the tracheobronchial tree have been described in the literature. These lesions occur with equal frequency in men and women; at a median age of 38 years; more frequently on the right than on the left; and most commonly with cough as the presenting symptom. Most patients have been treated with major surgical resections, but conservative endobronchial removal may be effective therapy."}
{"id": "PMID:212648", "title": "Coexistent bronchogenic carcinoma and active pulmonary tuberculosis.", "content": "Sixty-four cases of coexistent bronchogenic carcinoma and active pulmonary tuberculosis were diagnosed between 1969 and 1976. The majority were male chronic cigarette smokers in their fifth and sixth decades. Human bacilli were isolated in 48 patients (88.9 percent) and atypical bacilli in six patients (11.1 percent). All of the atypical bacilli and 8.3 percent of the human bacilli were found to be resistant to the first line antituberculous drugs. All patients, except two who died following resection, were given a course of antituberculous drugs with 93.8 percent successful sputum conversion. Uncontrolled or disseminated tuberculous infection was not observed. Forty-five patients (70.3 percent) underwent pulmonary resection. Median survival time of those who had curative resection was 14.3 months with a 5 year survival rate of 13.2 percent. Median survival times of those treated by palliative resection plus anticancer chemotherapy and by anticancer chemotherapy alone were 8.3 months and 11.1 months, respectively. None of these patients survived more than 30 months. It appears that, clinically, each disease runs its own course with little effect on the other.", "contents": "Coexistent bronchogenic carcinoma and active pulmonary tuberculosis. Sixty-four cases of coexistent bronchogenic carcinoma and active pulmonary tuberculosis were diagnosed between 1969 and 1976. The majority were male chronic cigarette smokers in their fifth and sixth decades. Human bacilli were isolated in 48 patients (88.9 percent) and atypical bacilli in six patients (11.1 percent). All of the atypical bacilli and 8.3 percent of the human bacilli were found to be resistant to the first line antituberculous drugs. All patients, except two who died following resection, were given a course of antituberculous drugs with 93.8 percent successful sputum conversion. Uncontrolled or disseminated tuberculous infection was not observed. Forty-five patients (70.3 percent) underwent pulmonary resection. Median survival time of those who had curative resection was 14.3 months with a 5 year survival rate of 13.2 percent. Median survival times of those treated by palliative resection plus anticancer chemotherapy and by anticancer chemotherapy alone were 8.3 months and 11.1 months, respectively. None of these patients survived more than 30 months. It appears that, clinically, each disease runs its own course with little effect on the other."}
{"id": "PMID:212650", "title": "Prostaglandins; their biological and pharmacological role.", "content": "The biological and pharmacological roles of prostaglandin system are reviewed. The most recent and important finding is the isolation and characterization of endoperoxides, thromboxanes and prostacyclin. In many respect they seem to be even more effective than the original prostaglandins and could explain many actions previously attributed to prostaglandins. Prostaglandins, endoperoxides, thromboxanes, and prostacyclin seem to have important physiological and pathophysiological roles, e.g. in the cardiovascular, gastro-intestinal and reproductive systems, the skin, and the central nervous system, as well as in inflammatory, immunological and metabolic reactions. Thus, prostaglandin-like substances, their analogues, prostaglandin antagonists, and the drugs that affect prostaglandin synthesis present good prospects for the treatment of many diseases affecting these systems. The mode of action of most anti-inflammatory and analgesic drugs can be explained by actions on the prostaglandin system. New potent and selective regulators of the prostaglandin system are being investigated and more indications are being found for using existing drugs. Although the field is generally promising, there are many contradictory findings. This calls for a cautious interpretation of the many interesting observations.", "contents": "Prostaglandins; their biological and pharmacological role. The biological and pharmacological roles of prostaglandin system are reviewed. The most recent and important finding is the isolation and characterization of endoperoxides, thromboxanes and prostacyclin. In many respect they seem to be even more effective than the original prostaglandins and could explain many actions previously attributed to prostaglandins. Prostaglandins, endoperoxides, thromboxanes, and prostacyclin seem to have important physiological and pathophysiological roles, e.g. in the cardiovascular, gastro-intestinal and reproductive systems, the skin, and the central nervous system, as well as in inflammatory, immunological and metabolic reactions. Thus, prostaglandin-like substances, their analogues, prostaglandin antagonists, and the drugs that affect prostaglandin synthesis present good prospects for the treatment of many diseases affecting these systems. The mode of action of most anti-inflammatory and analgesic drugs can be explained by actions on the prostaglandin system. New potent and selective regulators of the prostaglandin system are being investigated and more indications are being found for using existing drugs. Although the field is generally promising, there are many contradictory findings. This calls for a cautious interpretation of the many interesting observations."}
{"id": "PMID:212651", "title": "BK and Herpes simplex virus antibodies in renal cell carcinoma.", "content": "Serum antibodies against BK virus (BKV) and seven other viruses were studied in 76 patients with renal cell carcinoma using either the haemagglutination inhibition or the complement fixation techneque. BKV and herpes simplex virus (HSV), but no other virus antibodies, showed a clear correlation with the clinical course of renal carcinomas. The patients without BKV antibodies or with marginal antibody titres (titre less than or equal to 10), had a significantly longer observed expectation of life (O.E. life, 44.1 months) than the O.E. life (26.7 months) of the patients with BKV antibodies of titre less than or equal to 20. Similarly, patients with low or undetectable HSV antibodies (titre less than or equal to 8) also had significantly longer O.E. life (54.0 months) than the rest of the patients (32.7 months). The results suggest that BKV and HSV have an as yet underfined relationship to renal cell carcinomas.", "contents": "BK and Herpes simplex virus antibodies in renal cell carcinoma. Serum antibodies against BK virus (BKV) and seven other viruses were studied in 76 patients with renal cell carcinoma using either the haemagglutination inhibition or the complement fixation techneque. BKV and herpes simplex virus (HSV), but no other virus antibodies, showed a clear correlation with the clinical course of renal carcinomas. The patients without BKV antibodies or with marginal antibody titres (titre less than or equal to 10), had a significantly longer observed expectation of life (O.E. life, 44.1 months) than the O.E. life (26.7 months) of the patients with BKV antibodies of titre less than or equal to 20. Similarly, patients with low or undetectable HSV antibodies (titre less than or equal to 8) also had significantly longer O.E. life (54.0 months) than the rest of the patients (32.7 months). The results suggest that BKV and HSV have an as yet underfined relationship to renal cell carcinomas."}
{"id": "PMID:212654", "title": "Small cell anaplastic (oat cell) carcinoma of the larynx: report of a case and review of the literature.", "content": "The fifth reported patient with primary laryngeal oat cell carcinoma is described. Electron microscopy of tumor cells revealed typical neurosecretory-type granules similar to those described for pulmonary oat cell carcinoma. Analysis of clinical data from all five reported patients revealed that this neoplasm is a virulent one which spreads early and rapidly and kills quickly. Combination chemotherapy and/or radiotherapy, which has significantly prolonged life in patients with oat cell carcinoma of lung, may be indicated as an adjunct to surgery for this rare malignant tumor of the larynx.", "contents": "Small cell anaplastic (oat cell) carcinoma of the larynx: report of a case and review of the literature. The fifth reported patient with primary laryngeal oat cell carcinoma is described. Electron microscopy of tumor cells revealed typical neurosecretory-type granules similar to those described for pulmonary oat cell carcinoma. Analysis of clinical data from all five reported patients revealed that this neoplasm is a virulent one which spreads early and rapidly and kills quickly. Combination chemotherapy and/or radiotherapy, which has significantly prolonged life in patients with oat cell carcinoma of lung, may be indicated as an adjunct to surgery for this rare malignant tumor of the larynx."}
{"id": "PMID:212655", "title": "[Ethanol and lipid metabolism (author's transl)].", "content": "Fatty liver and hyperlipoproteinemia are the main clinical manifestations of interrelationships between ethanol and fat metabolism. Elevation of VLDL is observed more, hyperchylomicronemia less frequently. In metabolic healthy volunteers reversible hypertriglyceridemia can be provoked as well. The pathogenesis of ethanol-induced hyperlipoproteinemia is based on metabolic alterations directly dependent on the oxidation of ethanol in the liver as well as on indirect effects: Besides decreased oxidation and increased de-novo-synthesis by the liver, the sources of fatty acids for the enhanced production of VLDL are the adipose tissue and alimentary fat. VLDL concentrations have been shown to correlate with risk of atherogenesis in the middle-aged. Enhancement of alpha/beta (HDL/LDL)-cholesterol which would indicate an antiatherogenetic effect have been observed in relation to ethanol intake. At the moment it is premature to conclude that ethanol-induced changes in plasma lipoproteins may favour or delay atherogenesis.", "contents": "[Ethanol and lipid metabolism (author's transl)]. Fatty liver and hyperlipoproteinemia are the main clinical manifestations of interrelationships between ethanol and fat metabolism. Elevation of VLDL is observed more, hyperchylomicronemia less frequently. In metabolic healthy volunteers reversible hypertriglyceridemia can be provoked as well. The pathogenesis of ethanol-induced hyperlipoproteinemia is based on metabolic alterations directly dependent on the oxidation of ethanol in the liver as well as on indirect effects: Besides decreased oxidation and increased de-novo-synthesis by the liver, the sources of fatty acids for the enhanced production of VLDL are the adipose tissue and alimentary fat. VLDL concentrations have been shown to correlate with risk of atherogenesis in the middle-aged. Enhancement of alpha/beta (HDL/LDL)-cholesterol which would indicate an antiatherogenetic effect have been observed in relation to ethanol intake. At the moment it is premature to conclude that ethanol-induced changes in plasma lipoproteins may favour or delay atherogenesis."}
{"id": "PMID:212664", "title": "Binding and degradation of human 125I-HDL by rat adrenocortical cells.", "content": "In order to learn more about the mechanism by which high density lipoprotein (HDL) cholesterol is taken up by the adrenal cortex, binding and degradation of human 125I-HDL by suspensions of intact rat adrenal cortical cells have been examined. Cellular accumulation of 125I-HDL was found to occur in two phases. Our results indicate that the initial phase of association results from reversible binding of 125I-HDL to a specific saturable set of membrane binding sites. Binding site affinity appears equal for both rat and human HDL while affinity for human LDL is approximately one order of magnitude less on the basis of apoprotein weight. In addition, isolated rat adrenal cortical cells were found to degrade human 125I-HDL at a rapid rate. Degradation, like binding, can be prevented by addition of excess unlabeled HDL suggesting that binding and degradation are linked. Thus, one mechanism that could account for adrenal uptake of HDL cholesterol is endocytosis, initiated by lipoprotein binding to the HDL specific membrane binding site.", "contents": "Binding and degradation of human 125I-HDL by rat adrenocortical cells. In order to learn more about the mechanism by which high density lipoprotein (HDL) cholesterol is taken up by the adrenal cortex, binding and degradation of human 125I-HDL by suspensions of intact rat adrenal cortical cells have been examined. Cellular accumulation of 125I-HDL was found to occur in two phases. Our results indicate that the initial phase of association results from reversible binding of 125I-HDL to a specific saturable set of membrane binding sites. Binding site affinity appears equal for both rat and human HDL while affinity for human LDL is approximately one order of magnitude less on the basis of apoprotein weight. In addition, isolated rat adrenal cortical cells were found to degrade human 125I-HDL at a rapid rate. Degradation, like binding, can be prevented by addition of excess unlabeled HDL suggesting that binding and degradation are linked. Thus, one mechanism that could account for adrenal uptake of HDL cholesterol is endocytosis, initiated by lipoprotein binding to the HDL specific membrane binding site."}
{"id": "PMID:212665", "title": "Lipoprotein lipase activity in adipose tissue and skeletal muscle of runners: relation to serum lipoproteins.", "content": "Physically well-trained people generally have lower VLDL-triglyceride and higher HDL-cholesterol levels than sedentary subjects. To examine the underlying mechanisms of this lipoprotein pattern, we measured the lipoprotein lipase (LPL) activity in needle biopsy specimens of adipose tissue and skeletal muscle of competitive runners and of body weight-matched, physically less-active controls. The active sportsmen were either sprinters, whose training program consisted mainly of athletics of short duration or long distance runners undergoing a strenuous endurance exercise program. In sprinters (all males) the serum lipid and lipoprotein concentrations did not differ significantly from those of controls and the mean LPL activities in muscle and adipose tissue were also similar in these two groups. The long distance runners (both sexes), on the other hand, had higher means levels of HDL-cholesterol than the respective controls. The LPL-activity of both adipose tissue (p less than 0.05) and skeletal muscle (p less than 0.01) was significantly higher in male long distance runners than in control males. Female runners had higher muscle LPL activity than controls (p less than 0.01) but in adipose tissue the difference in LPL activity was not significant. Rough estimates calculated for LPL activity present in whole body adipose tissue and skeletal muscle indicated that total LPL activity was 2.3 times higher in male long distance runners and 1.5 times higher in female long distance runners than in the respective controls. In combined groups of male runners and controls, there was a highly significant positive correlation between the serum HDL-cholesterol level and the LPL activity of adipose tissue expressed per tissue weight (r = +0.72, p less than 0.001) or per whole body fat (r = +0.62, p less than 0.001). The group means of HDL-cholesterol and adipose tissue LPL activity in the five cohorts studied (male sprinters, distance runners and controls and female distance runners and controls) were also positively correlated (r = +0.94). It is concluded that endurance training is associated with an adaptive increase of LPL activity not only in skeletal muscle but also in adipose tissue. These changes are not observed in sprinters who are trained by exercises of shorter duration. The high HDL-cholesterol levels of physically well-trained people are probably accounted for, at least partly, by the increased LPL activity and the concomitant rapid turnover or triglyceride-rich lipoproteins.", "contents": "Lipoprotein lipase activity in adipose tissue and skeletal muscle of runners: relation to serum lipoproteins. Physically well-trained people generally have lower VLDL-triglyceride and higher HDL-cholesterol levels than sedentary subjects. To examine the underlying mechanisms of this lipoprotein pattern, we measured the lipoprotein lipase (LPL) activity in needle biopsy specimens of adipose tissue and skeletal muscle of competitive runners and of body weight-matched, physically less-active controls. The active sportsmen were either sprinters, whose training program consisted mainly of athletics of short duration or long distance runners undergoing a strenuous endurance exercise program. In sprinters (all males) the serum lipid and lipoprotein concentrations did not differ significantly from those of controls and the mean LPL activities in muscle and adipose tissue were also similar in these two groups. The long distance runners (both sexes), on the other hand, had higher means levels of HDL-cholesterol than the respective controls. The LPL-activity of both adipose tissue (p less than 0.05) and skeletal muscle (p less than 0.01) was significantly higher in male long distance runners than in control males. Female runners had higher muscle LPL activity than controls (p less than 0.01) but in adipose tissue the difference in LPL activity was not significant. Rough estimates calculated for LPL activity present in whole body adipose tissue and skeletal muscle indicated that total LPL activity was 2.3 times higher in male long distance runners and 1.5 times higher in female long distance runners than in the respective controls. In combined groups of male runners and controls, there was a highly significant positive correlation between the serum HDL-cholesterol level and the LPL activity of adipose tissue expressed per tissue weight (r = +0.72, p less than 0.001) or per whole body fat (r = +0.62, p less than 0.001). The group means of HDL-cholesterol and adipose tissue LPL activity in the five cohorts studied (male sprinters, distance runners and controls and female distance runners and controls) were also positively correlated (r = +0.94). It is concluded that endurance training is associated with an adaptive increase of LPL activity not only in skeletal muscle but also in adipose tissue. These changes are not observed in sprinters who are trained by exercises of shorter duration. The high HDL-cholesterol levels of physically well-trained people are probably accounted for, at least partly, by the increased LPL activity and the concomitant rapid turnover or triglyceride-rich lipoproteins."}
{"id": "PMID:212670", "title": "[Regulation of the biosynthesis of extracellular phosphohydrolases in Penicillium brevicompactum].", "content": "The effect of certain metabolites of Penicillium brevi-compactum on the biosynthesis of exocellular ribonucleases and phosphomonoesterase was studied. Their synthesis was found to be inhibited by RNA and AMP, as well as by high concentrations of these enzymes in the medium. The mechanism which regulates the biosynthesis of exocellular phosphohydrolases by both phosphate and the enzymes is discussed.", "contents": "[Regulation of the biosynthesis of extracellular phosphohydrolases in Penicillium brevicompactum]. The effect of certain metabolites of Penicillium brevi-compactum on the biosynthesis of exocellular ribonucleases and phosphomonoesterase was studied. Their synthesis was found to be inhibited by RNA and AMP, as well as by high concentrations of these enzymes in the medium. The mechanism which regulates the biosynthesis of exocellular phosphohydrolases by both phosphate and the enzymes is discussed."}
{"id": "PMID:212671", "title": "[Use of the electron paramagnetic resonance method for the comparative evaluation of the effectiveness of the protective media used in the lyophilization of actimomycetes].", "content": "The accumulation of free radicals correlates with an increase in the percentage of killed lyophilized spores of actinomycetes. Therefore, the EPR method in combination with the method of \"accelerated storage\" at 37 degrees C was used to evaluate rapidly (during one month) the effectiveness and to select certain protective media for stabilization of actinomycetes cultures. The EPR method can be applied for comparative evaluation of only those media which did not contain originally free radicals.", "contents": "[Use of the electron paramagnetic resonance method for the comparative evaluation of the effectiveness of the protective media used in the lyophilization of actimomycetes]. The accumulation of free radicals correlates with an increase in the percentage of killed lyophilized spores of actinomycetes. Therefore, the EPR method in combination with the method of \"accelerated storage\" at 37 degrees C was used to evaluate rapidly (during one month) the effectiveness and to select certain protective media for stabilization of actinomycetes cultures. The EPR method can be applied for comparative evaluation of only those media which did not contain originally free radicals."}
{"id": "PMID:212672", "title": "[Ethylmethane sulfonate induction of auxotrophic mutants of Rhizobium meliloti and their characteristics].", "content": "Ethylmethanesulfonate was used as a mutagen to induce auxotrophic mutants in Rhizobium meliloti L5-30. Survival of the culture depended on the period of time during which it was treated with the mutagen. Thirteen auxotrophic mutants were isolated as a result of screening 1404 clones, and their requirements in growtn factors were determined. Ethylmethanesulfonate induced mainly those mutants which required sulfur-containing amino acids. The activity of nitrogen fixation of the auxotrophic mutants was assayed by measuring the reduction of acetylene and the yield of lucerne. Mutants requiring methionine or cystein, cysteine or histidine, and adenine with thiamine were not effective whereas those requiring arginine, tryptophan, and thiamine were capable of nitrogen fixation. Among two methionine auxotrophs, one displayed the activity of nitrogen fixation and the other did not.", "contents": "[Ethylmethane sulfonate induction of auxotrophic mutants of Rhizobium meliloti and their characteristics]. Ethylmethanesulfonate was used as a mutagen to induce auxotrophic mutants in Rhizobium meliloti L5-30. Survival of the culture depended on the period of time during which it was treated with the mutagen. Thirteen auxotrophic mutants were isolated as a result of screening 1404 clones, and their requirements in growtn factors were determined. Ethylmethanesulfonate induced mainly those mutants which required sulfur-containing amino acids. The activity of nitrogen fixation of the auxotrophic mutants was assayed by measuring the reduction of acetylene and the yield of lucerne. Mutants requiring methionine or cystein, cysteine or histidine, and adenine with thiamine were not effective whereas those requiring arginine, tryptophan, and thiamine were capable of nitrogen fixation. Among two methionine auxotrophs, one displayed the activity of nitrogen fixation and the other did not."}
{"id": "PMID:212673", "title": "[Cytomorphology of the lipid inclusions of Caryophanon during its growth on an agarized medium].", "content": "The cytomorphology of lipid inclusions of Caryophanon latum and Caryophanon tenue was studied in the course of their growth on a solid medium. The paper presents a detailed scheme and microphotographs showing cytomorphological changes in the inclusions of the cultures under study. Staining of the preparations with the lipophilic dye Sudan Black B revealed two types of sudanophilic granules which varied in their location within trichomes, the time at which they appeared in bacteria, and their behaviour toward solvents. These lipid inclusions of Caryophanon are mainly represented by the polymer poly-beta-hydroxybutyric acid.", "contents": "[Cytomorphology of the lipid inclusions of Caryophanon during its growth on an agarized medium]. The cytomorphology of lipid inclusions of Caryophanon latum and Caryophanon tenue was studied in the course of their growth on a solid medium. The paper presents a detailed scheme and microphotographs showing cytomorphological changes in the inclusions of the cultures under study. Staining of the preparations with the lipophilic dye Sudan Black B revealed two types of sudanophilic granules which varied in their location within trichomes, the time at which they appeared in bacteria, and their behaviour toward solvents. These lipid inclusions of Caryophanon are mainly represented by the polymer poly-beta-hydroxybutyric acid."}
{"id": "PMID:212674", "title": "[Electron microscopic data on the mesosomelike and myelinlike structures of blue-green algae].", "content": "The mesosome-like structures of blue-green algae were studied by freeze-etching without preliminary fixation and, in parallel, by a technique of ultrathin sections. These structures were found mainly in Synechococcus elongatus and Synechocystis aquatilis, less often, in Anacystis nidulans and Anabaena variabilis, and were not detected in Plectonema boryanum. The following types of membrane structures were encountered: (1) formation consisting of three- and five-layered membranes and resembling the lamellar mesosomes of bacteria; (2) complex structures consisting of five-layered membranes and separated from the cytoplasm by an electron-dense substance not found in bacteria; (3) myelin-like structures; (4) formations intermediate between the mesosome-like and myelin-like structures. These structures were not found to be strictly confined to the growth phase of a culture. Possible functions of the mesosome-like and myelin-like structures are discussed ct. those of bacteria.", "contents": "[Electron microscopic data on the mesosomelike and myelinlike structures of blue-green algae]. The mesosome-like structures of blue-green algae were studied by freeze-etching without preliminary fixation and, in parallel, by a technique of ultrathin sections. These structures were found mainly in Synechococcus elongatus and Synechocystis aquatilis, less often, in Anacystis nidulans and Anabaena variabilis, and were not detected in Plectonema boryanum. The following types of membrane structures were encountered: (1) formation consisting of three- and five-layered membranes and resembling the lamellar mesosomes of bacteria; (2) complex structures consisting of five-layered membranes and separated from the cytoplasm by an electron-dense substance not found in bacteria; (3) myelin-like structures; (4) formations intermediate between the mesosome-like and myelin-like structures. These structures were not found to be strictly confined to the growth phase of a culture. Possible functions of the mesosome-like and myelin-like structures are discussed ct. those of bacteria."}
{"id": "PMID:212678", "title": "Epidemiology of human rotavirus Types 1 and 2 as studied by enzyme-linked immunosorbent assay.", "content": "To determine the relative importance of two known serotypes of human rotavirus, we developed an enzyme-linked immunosorbent assay to differentiate serotype-specific rotavirus antigen and antibody. Using this technic, we studied the epidemiology of the two serotypes in acute gastroenteritis. Seventy-seven per cent of 414 rotavirus isolates were Type 2, and the remainder were Type 1. The serotype distribution was similar in specimens from children in Washington, D.C., and other parts of the world. Sero-epidemiologic studies revealed that most children living in the Washington, D.C., area acquired antibody to both types by the age of two years. An analysis of children who were reinfected indicated that sequential infections usually involved different serotypes and that illness caused by one serotype did not provide resistance to illness caused by the other serotype. These results suggest that, to be completely effective, a vaccine must provide resistance to both serotypes.", "contents": "Epidemiology of human rotavirus Types 1 and 2 as studied by enzyme-linked immunosorbent assay. To determine the relative importance of two known serotypes of human rotavirus, we developed an enzyme-linked immunosorbent assay to differentiate serotype-specific rotavirus antigen and antibody. Using this technic, we studied the epidemiology of the two serotypes in acute gastroenteritis. Seventy-seven per cent of 414 rotavirus isolates were Type 2, and the remainder were Type 1. The serotype distribution was similar in specimens from children in Washington, D.C., and other parts of the world. Sero-epidemiologic studies revealed that most children living in the Washington, D.C., area acquired antibody to both types by the age of two years. An analysis of children who were reinfected indicated that sequential infections usually involved different serotypes and that illness caused by one serotype did not provide resistance to illness caused by the other serotype. These results suggest that, to be completely effective, a vaccine must provide resistance to both serotypes."}
{"id": "PMID:212684", "title": "Subsensitivity of the rat striatal dopaminergic system after treatment with bromocriptine: effects on [3H]spiperone binding and dopamine-stimulated cyclic AMP formation.", "content": "Repeated daily administration of the dopamine (DA) agonist bromocriptine (15 mg/kg; s.cut.) to rats led to a time dependent decrease in the in vitro binding of [3H]spiperone to striatal membranes. Kinetic analysis of [3H]spiperone binding after 2 and 7 days of bromocriptine treatment showed a 25-50% reduction in the total number of binding sites with no changein their affinity for spiperone. There was also a decreased accumulation of cyclic AMP (cAMP) in striatal slices in response to DA after bromocriptine treatment. The DA-sensitive adenylate cyclase in striatal homogenates, however, remained unchanged in bromocriptine treated rats. There was also no change in cyclic nucleotide phosphodiesterase activity in striatal tissue after bromocriptine treatment. Furthermore, incubation of striatal slices in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine did not alter the decreased cAMP response to DA after 2 days of bromocriptine treatment. These results suggest that a decreased number of DA receptor sites may be responsible for the reduced cAMP response to DA in striatal slices after bromocriptine treatment.", "contents": "Subsensitivity of the rat striatal dopaminergic system after treatment with bromocriptine: effects on [3H]spiperone binding and dopamine-stimulated cyclic AMP formation. Repeated daily administration of the dopamine (DA) agonist bromocriptine (15 mg/kg; s.cut.) to rats led to a time dependent decrease in the in vitro binding of [3H]spiperone to striatal membranes. Kinetic analysis of [3H]spiperone binding after 2 and 7 days of bromocriptine treatment showed a 25-50% reduction in the total number of binding sites with no changein their affinity for spiperone. There was also a decreased accumulation of cyclic AMP (cAMP) in striatal slices in response to DA after bromocriptine treatment. The DA-sensitive adenylate cyclase in striatal homogenates, however, remained unchanged in bromocriptine treated rats. There was also no change in cyclic nucleotide phosphodiesterase activity in striatal tissue after bromocriptine treatment. Furthermore, incubation of striatal slices in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine did not alter the decreased cAMP response to DA after 2 days of bromocriptine treatment. These results suggest that a decreased number of DA receptor sites may be responsible for the reduced cAMP response to DA in striatal slices after bromocriptine treatment."}
{"id": "PMID:212685", "title": "Reduction of the equilibrium binding of cardiac glycosides and related compounds to Na+,K+-ATPase as a possible mechanism for the potassium-induced reversal of their toxicity.", "content": "The influence of potassium ions on the equilibrium state of the binding of cardiac glycosides and their derivatives to partially purified dog heart and rat brain enzyme preparations was studied in vitro. The addition of potassium to the incubation mixture containing enzyme preparation, 3H-ouabain, Na+, Mg2+ and ATP, at the time when the binding reaction is close to equilibrium, caused an immediate reduction of the bound drug concentration; the concentration apparently shifting toward a lower equilibrium state. The degree of the potassium-induced reduction in bound drug concentration was dependent on the potassium concentration and on the chemical structure of the compound. The binding of aglycones, pentacetyl-gitoxin and cassaine was affected to a greater extent than that of the glycosides. These data suggest that one of the mechanisms by which potassium antagonizes the toxic actions of digitalis on the heart is to reduce the drug binding to cardiac Na+,K+-ATPase.", "contents": "Reduction of the equilibrium binding of cardiac glycosides and related compounds to Na+,K+-ATPase as a possible mechanism for the potassium-induced reversal of their toxicity. The influence of potassium ions on the equilibrium state of the binding of cardiac glycosides and their derivatives to partially purified dog heart and rat brain enzyme preparations was studied in vitro. The addition of potassium to the incubation mixture containing enzyme preparation, 3H-ouabain, Na+, Mg2+ and ATP, at the time when the binding reaction is close to equilibrium, caused an immediate reduction of the bound drug concentration; the concentration apparently shifting toward a lower equilibrium state. The degree of the potassium-induced reduction in bound drug concentration was dependent on the potassium concentration and on the chemical structure of the compound. The binding of aglycones, pentacetyl-gitoxin and cassaine was affected to a greater extent than that of the glycosides. These data suggest that one of the mechanisms by which potassium antagonizes the toxic actions of digitalis on the heart is to reduce the drug binding to cardiac Na+,K+-ATPase."}
{"id": "PMID:212686", "title": "Effects of lithium and thallous ions on sodium pump activity in the guinea-pig heart and their relationship to the positive inotropic action.", "content": "It has recently been demonstrated that both Tl+ and Li+ produce concentration- and time-dependent positive inotropic effects in guinea-pig atrial preparations although Tl+ inhibits and Li+ stimulates isolated Na+,K+-ATPase in vitro. In order to elucidate the mechanism of the positive inotropic actions of these cations, the effects of Tl+ and Li+ on sodium pump activity were studied. Active 86Rb uptake in guinea-pig ventricular slices, an estimate of sodium pump activity, was highly sensitive to the inhibitory effect of the cardiac glycosides. Preincubation of slices with Tl+ caused a dose- and time-dependent inhibition of active 86Rb uptake. Similar concentration- and time-dependent inhibition of active 86Rb uptake was observed when Na+ in a Krebs-Henseleit solution was partially replaced with Li+. Lithium, however, stimulated a partially purified Na+,K+-ATPase in vitro. During heart slice incubation, Tl+ and Li+ accumulated in a time-dependent manner. This accumulation was not readily reversible when slices were transferred into Tl+- or Li+-free solutions. It appears that the inhibition of sodium pump activity is related to the positive inotropic action of these cations.", "contents": "Effects of lithium and thallous ions on sodium pump activity in the guinea-pig heart and their relationship to the positive inotropic action. It has recently been demonstrated that both Tl+ and Li+ produce concentration- and time-dependent positive inotropic effects in guinea-pig atrial preparations although Tl+ inhibits and Li+ stimulates isolated Na+,K+-ATPase in vitro. In order to elucidate the mechanism of the positive inotropic actions of these cations, the effects of Tl+ and Li+ on sodium pump activity were studied. Active 86Rb uptake in guinea-pig ventricular slices, an estimate of sodium pump activity, was highly sensitive to the inhibitory effect of the cardiac glycosides. Preincubation of slices with Tl+ caused a dose- and time-dependent inhibition of active 86Rb uptake. Similar concentration- and time-dependent inhibition of active 86Rb uptake was observed when Na+ in a Krebs-Henseleit solution was partially replaced with Li+. Lithium, however, stimulated a partially purified Na+,K+-ATPase in vitro. During heart slice incubation, Tl+ and Li+ accumulated in a time-dependent manner. This accumulation was not readily reversible when slices were transferred into Tl+- or Li+-free solutions. It appears that the inhibition of sodium pump activity is related to the positive inotropic action of these cations."}
{"id": "PMID:212687", "title": "The opiate-like action of tilidine is mediated by metabolites.", "content": "The analgesic effect of tilidine in rats is completely antagonized by the narcotic antagonist naloxone. Radioreceptor assays revealed, however, that the main metabolites of tilidine, nortilidine and bisnortilidine, rather than tilidine exhibit affinity to opiate receptors. These findings were confirmed in studies using the electrically stimulated guinea pig ileum and the mouse vas deferens. Chronic tilidine administration to rats caused a considerable degree of physical dependence, which was expected from the ability of the intact animal to metabolize tilidine. In the isolated ileum from chronically morphinized guinea pigs, both nortilidine and bisnortilidine fully substituted for morphine in preventing induction of withdrawal, indicating dependence liability of these metabolites.", "contents": "The opiate-like action of tilidine is mediated by metabolites. The analgesic effect of tilidine in rats is completely antagonized by the narcotic antagonist naloxone. Radioreceptor assays revealed, however, that the main metabolites of tilidine, nortilidine and bisnortilidine, rather than tilidine exhibit affinity to opiate receptors. These findings were confirmed in studies using the electrically stimulated guinea pig ileum and the mouse vas deferens. Chronic tilidine administration to rats caused a considerable degree of physical dependence, which was expected from the ability of the intact animal to metabolize tilidine. In the isolated ileum from chronically morphinized guinea pigs, both nortilidine and bisnortilidine fully substituted for morphine in preventing induction of withdrawal, indicating dependence liability of these metabolites."}
{"id": "PMID:212688", "title": "[Interaction of heterosensory afferent impulses in the neurons of the thalamic associative nuclei].", "content": "The interaction of visual, auditory and cutaneous afferent signals on neurons of pulvinar (Pulv), posterior lateral (LP) and mediodorsal (MD) thalamic nuclei was studied in acute experiments on cats anaesthetized with a mixture of nembutal and chloralorse. The first (more frequent) type of the interaction was characterized by inhibition or inhibition followed by facilitation of the response; the second--by facilitation or facilitation followed by inhibition of neuronal activity. The capacity for interaction in MD neurons was less expressed than in cells of the Pulv-LP complex (P less than 0.05). The interaction could be better seen in three-sensory elements. Certain peculiarities were found in the interaction of afferent signals coming from different peripheral receptive areas in neurons of both structures.", "contents": "[Interaction of heterosensory afferent impulses in the neurons of the thalamic associative nuclei]. The interaction of visual, auditory and cutaneous afferent signals on neurons of pulvinar (Pulv), posterior lateral (LP) and mediodorsal (MD) thalamic nuclei was studied in acute experiments on cats anaesthetized with a mixture of nembutal and chloralorse. The first (more frequent) type of the interaction was characterized by inhibition or inhibition followed by facilitation of the response; the second--by facilitation or facilitation followed by inhibition of neuronal activity. The capacity for interaction in MD neurons was less expressed than in cells of the Pulv-LP complex (P less than 0.05). The interaction could be better seen in three-sensory elements. Certain peculiarities were found in the interaction of afferent signals coming from different peripheral receptive areas in neurons of both structures."}
{"id": "PMID:212689", "title": "[Reactions of cat hindbrain \"locomotor strip\" neurons to microstimulation].", "content": "Synaptic responses of single neurons in the locomotor strip\" were recorded extracellularly. Neurons of the rostral part of the strip produced short-latency responses to stimulation of the mesencephalic \"locomotor region\". Neurons of the caudal part of the strip responded to microstimulation of other sites of the strip, rostral ones included. When the distance between the site of stimulation and a neuron along the strip was less than 2--3 mm, short-latency (1.2--1.6 ms) responses were recorded. Thresholds and latencies grew with the distance. Polysynaptic responses with a 3--4 ms latency could be potentiated when repetitive (30--40 pulses per s) stimulation was used instead of a single stimulus. The results suggest that axons in the \"locomotor strip\" are oriented in a rostrocaudal direction and give off collaterals to neighbour neurons. The \"locomotor strip\" can be an integrative centre \"intercalated\" between the rostral centers of the brain and the spinal cord.", "contents": "[Reactions of cat hindbrain \"locomotor strip\" neurons to microstimulation]. Synaptic responses of single neurons in the locomotor strip\" were recorded extracellularly. Neurons of the rostral part of the strip produced short-latency responses to stimulation of the mesencephalic \"locomotor region\". Neurons of the caudal part of the strip responded to microstimulation of other sites of the strip, rostral ones included. When the distance between the site of stimulation and a neuron along the strip was less than 2--3 mm, short-latency (1.2--1.6 ms) responses were recorded. Thresholds and latencies grew with the distance. Polysynaptic responses with a 3--4 ms latency could be potentiated when repetitive (30--40 pulses per s) stimulation was used instead of a single stimulus. The results suggest that axons in the \"locomotor strip\" are oriented in a rostrocaudal direction and give off collaterals to neighbour neurons. The \"locomotor strip\" can be an integrative centre \"intercalated\" between the rostral centers of the brain and the spinal cord."}
{"id": "PMID:212692", "title": "[Hypogenic cholinergic neuronal route in the central nervous system].", "content": "Because of the extensive overlapping within the brain of arousing and hypnogenic neurons the method of electrical stimulation has proved unsuitable for mapping out specific hypnogenic structures. On the other hand, the method of localized chemical stimulation achieved by introducing minute crystals of chemical substances permits the dissection of adjacent neurons with different functions. The aim of this study was to map out the central hypnogenic pathways introducing minute crystals of acetylcholine, eserine or atropine in different brain regions through cannulae permanently implanted in the brains of cats. The behavioral effects produced by the chemical stimulus were monitored simultaneously with electrical recordings from the neocortex, olfactory bulb, enthorinal cortex, and eyes movements. It is concluded that there is a sleep system made up of a multisynaptic chain of short axon neurons with cholinergic synaptic transmission and which extends throughout all the levels of the neuroaxis.", "contents": "[Hypogenic cholinergic neuronal route in the central nervous system]. Because of the extensive overlapping within the brain of arousing and hypnogenic neurons the method of electrical stimulation has proved unsuitable for mapping out specific hypnogenic structures. On the other hand, the method of localized chemical stimulation achieved by introducing minute crystals of chemical substances permits the dissection of adjacent neurons with different functions. The aim of this study was to map out the central hypnogenic pathways introducing minute crystals of acetylcholine, eserine or atropine in different brain regions through cannulae permanently implanted in the brains of cats. The behavioral effects produced by the chemical stimulus were monitored simultaneously with electrical recordings from the neocortex, olfactory bulb, enthorinal cortex, and eyes movements. It is concluded that there is a sleep system made up of a multisynaptic chain of short axon neurons with cholinergic synaptic transmission and which extends throughout all the levels of the neuroaxis."}
{"id": "PMID:212694", "title": "Fatty acid composition of myelin lipids (cerebrosides, sulphatides and sphingomyelin) from normal human sural nerve, and changes in peripheral neuropathy.", "content": "Fatty acids of cerebrosides, sulphatides and sphingomyelin from normal human sural nerve, by comparison with brain, show a diminution of long-chained fatty acids as well as unsaturated fatty acids. The findings in brachial plexus are intermediate. In cases of peripheral neuropathy from various causes sphingomyelin fatty acid composition reveals pronounced loss of long-chained fatty acids, a phenomenon that is probably unspecific and may be associated with all forms of demyelination. Problems associated with the limited amount of nervous tissue available from biopsy specimens are discussed.", "contents": "Fatty acid composition of myelin lipids (cerebrosides, sulphatides and sphingomyelin) from normal human sural nerve, and changes in peripheral neuropathy. Fatty acids of cerebrosides, sulphatides and sphingomyelin from normal human sural nerve, by comparison with brain, show a diminution of long-chained fatty acids as well as unsaturated fatty acids. The findings in brachial plexus are intermediate. In cases of peripheral neuropathy from various causes sphingomyelin fatty acid composition reveals pronounced loss of long-chained fatty acids, a phenomenon that is probably unspecific and may be associated with all forms of demyelination. Problems associated with the limited amount of nervous tissue available from biopsy specimens are discussed."}
{"id": "PMID:212695", "title": "A quantitative histological study of changes in neurons and glia in the Gunn rat brain.", "content": "The rostral part of the anterior limb of the anterior commissure (RAL) and the indusium griseum of the brains of Gunn rats and Wistar rats were examined quantitatively to assess the effects of hyperbilirubinaemia on the developing nervous system. The number of glia in the RAL was significantly less in Gunn rats than in the Wistar rats. The number of glia in the indusium griseum was similar in both groups but the Gunn rats showed a decrease of about 20% in the number of neutrons in this region. Myelination appeared to be unaffected and apart from an apparent increase in the number of dense bodies in astrocytes and oligodendrocytes there were no obvious morphological changes in either glia or neurons.", "contents": "A quantitative histological study of changes in neurons and glia in the Gunn rat brain. The rostral part of the anterior limb of the anterior commissure (RAL) and the indusium griseum of the brains of Gunn rats and Wistar rats were examined quantitatively to assess the effects of hyperbilirubinaemia on the developing nervous system. The number of glia in the RAL was significantly less in Gunn rats than in the Wistar rats. The number of glia in the indusium griseum was similar in both groups but the Gunn rats showed a decrease of about 20% in the number of neutrons in this region. Myelination appeared to be unaffected and apart from an apparent increase in the number of dense bodies in astrocytes and oligodendrocytes there were no obvious morphological changes in either glia or neurons."}
{"id": "PMID:212696", "title": "Anterior pituitary function before and after trans-sphenoidal microsurgical resection of pituitary tumors.", "content": "Anterior pituitary lobe function was measured pre- and postoperatively in 40 patients with pituitary tumors who were managed surgically by the trans-sphenoidal approach. Of 23 patients with normal anterior lobe function preoperatively, 21 (91%) were normal postoperatively. Of 17 preoperatively impaired patients, 7 (40%) regained normal function, 3 (18%) improved, 4 (24%) remained the same, and 3 (18%) were further impaired by the surgery. In this small series, the likelihood of recovery of pituitary function varied inversely with the degree of preoperative impairment and the size of the tumor, suggesting that more aggressive surgical management of small, minimally symptomatic pituitary tumors is justified.", "contents": "Anterior pituitary function before and after trans-sphenoidal microsurgical resection of pituitary tumors. Anterior pituitary lobe function was measured pre- and postoperatively in 40 patients with pituitary tumors who were managed surgically by the trans-sphenoidal approach. Of 23 patients with normal anterior lobe function preoperatively, 21 (91%) were normal postoperatively. Of 17 preoperatively impaired patients, 7 (40%) regained normal function, 3 (18%) improved, 4 (24%) remained the same, and 3 (18%) were further impaired by the surgery. In this small series, the likelihood of recovery of pituitary function varied inversely with the degree of preoperative impairment and the size of the tumor, suggesting that more aggressive surgical management of small, minimally symptomatic pituitary tumors is justified."}
{"id": "PMID:212702", "title": "Adenoid cystic carcinoma of the Cervix. Report of 9 cases and a reappraisal.", "content": "The clinical and pathologic findings of 9 patients with adenoid cystic carcinoma of the cervix are presented. A review of the literature identified an additional 29 cases. The tumor was usually associated with adenocarcinoma or squamous cell carcinoma of the cervix. Adenoid cystic carcinoma of the cervix appears to be an aggressive type of tumor; of the 38 cases reported in the literature lung metastases have occurred in 18 (47.4%), and of these, 14 patients are known to have died of the cancer.", "contents": "Adenoid cystic carcinoma of the Cervix. Report of 9 cases and a reappraisal. The clinical and pathologic findings of 9 patients with adenoid cystic carcinoma of the cervix are presented. A review of the literature identified an additional 29 cases. The tumor was usually associated with adenocarcinoma or squamous cell carcinoma of the cervix. Adenoid cystic carcinoma of the cervix appears to be an aggressive type of tumor; of the 38 cases reported in the literature lung metastases have occurred in 18 (47.4%), and of these, 14 patients are known to have died of the cancer."}
{"id": "PMID:212708", "title": "Dual effect of external calcium on the frequency of miniature synaptic potentials in frog sympathetic ganglion cells.", "content": "The effect of calcium on spontaneous transmitter release and on the release induced by tetanic stimulation and by raising the external potassium concentration ([K]0) was studied in sympathetic ganglion cells of Rana esculenta. 1. In standard Ringer's solution the frequency of miniature excitatory postsynaptic potentials (mepsp) ranged from 0.05--2.0 s-1 (0.05 +/- 0.09 s-1, n = 37) at room temperature. 2. At a [K]0 of 2.5 mM mepsp frequency was approximately linearly related to the logarithm of the external calcium concentration (log [Ca]0) (0.1 mM less than or equal to [Ca]0 less than or equal to 20 mM). 3. Duration and amplitude of the potentiation of transmitter release after tetanic preganglionic stimulation increased depending on [Ca]0. 4. Mepsp frequency was strongly dependent on [K]0 between 10 and 20 mM; the frequency being increased to about 40 times control level at a [K]0 of 20 mM. 5. Raising [Ca]0 up to 1.8 mM in high K solutions resulted in an increase in mepsp frequency followed by a decrease at higher [Ca]0. 6. These results are consistent with the idea that the effect of calcium on mepsp frequency depends on: (a) the driving force for calcium entry, (b) the effect of Ca ions on the potential gradient within the nerve membrane.", "contents": "Dual effect of external calcium on the frequency of miniature synaptic potentials in frog sympathetic ganglion cells. The effect of calcium on spontaneous transmitter release and on the release induced by tetanic stimulation and by raising the external potassium concentration ([K]0) was studied in sympathetic ganglion cells of Rana esculenta. 1. In standard Ringer's solution the frequency of miniature excitatory postsynaptic potentials (mepsp) ranged from 0.05--2.0 s-1 (0.05 +/- 0.09 s-1, n = 37) at room temperature. 2. At a [K]0 of 2.5 mM mepsp frequency was approximately linearly related to the logarithm of the external calcium concentration (log [Ca]0) (0.1 mM less than or equal to [Ca]0 less than or equal to 20 mM). 3. Duration and amplitude of the potentiation of transmitter release after tetanic preganglionic stimulation increased depending on [Ca]0. 4. Mepsp frequency was strongly dependent on [K]0 between 10 and 20 mM; the frequency being increased to about 40 times control level at a [K]0 of 20 mM. 5. Raising [Ca]0 up to 1.8 mM in high K solutions resulted in an increase in mepsp frequency followed by a decrease at higher [Ca]0. 6. These results are consistent with the idea that the effect of calcium on mepsp frequency depends on: (a) the driving force for calcium entry, (b) the effect of Ca ions on the potential gradient within the nerve membrane."}
{"id": "PMID:212709", "title": "NAD in muscle of man at rest and during exercise.", "content": "NAD can be used to assess the adequacy of oxygen availability to the respiratory chain. An enzymatic assay was established for NAD in human muscle biopsy samples. It gave reliable, reproducible results. The variation within and between subjects was less than 12%. Muscle NAD and lactate were determined at rest, and after bicycle ergometry work requiring approximately 75 and approximately 100% VO2 max (six subjects, four tests each). A positive (P less than 0.01) linear relationship between resting muscle NAD and percent slow twitch fibers was found, suggesting that fiber types may have different NAD content. Muscle NAD decreased during submaximal and maximal work (P less than 0.05). A large portion (73%) of the NAD reduction could be accounted for by increased muscle water. No relationship could be established between NAD and lactate. The negative linear relationship (P less than 0.01) between the muscle/blood ratio and percent slow twitch fibers is another indication of the fiber having different metabolic responses to the activity.", "contents": "NAD in muscle of man at rest and during exercise. NAD can be used to assess the adequacy of oxygen availability to the respiratory chain. An enzymatic assay was established for NAD in human muscle biopsy samples. It gave reliable, reproducible results. The variation within and between subjects was less than 12%. Muscle NAD and lactate were determined at rest, and after bicycle ergometry work requiring approximately 75 and approximately 100% VO2 max (six subjects, four tests each). A positive (P less than 0.01) linear relationship between resting muscle NAD and percent slow twitch fibers was found, suggesting that fiber types may have different NAD content. Muscle NAD decreased during submaximal and maximal work (P less than 0.05). A large portion (73%) of the NAD reduction could be accounted for by increased muscle water. No relationship could be established between NAD and lactate. The negative linear relationship (P less than 0.01) between the muscle/blood ratio and percent slow twitch fibers is another indication of the fiber having different metabolic responses to the activity."}
{"id": "PMID:212713", "title": "[Sterologic evaluation on in vitro thrombin-induced platelet degranulation and contraction (author's transl)].", "content": "Stereologic study of the in vitro release reaction from unstirred washed platelets provided quantitative information on the contractile wave induced by thrombin. Contraction was estimated from the reduction in the volume of both the granular compartment and the vacuoles of the surface connected canalicular system. Dibutyryl cyclic-AMP (10(-4) M) and dipyridamole (10(-3) M) inhibited degranulation, but they had no effect on the contraction produced by thrombin at high concentrations (0.1 UI/ml). Aspirin (10(-4) M) inhibited contraction induced by thrombin at concentration of 0.1 and 0.02 UI/ml (p less than 0.01 at each concentration). In two patients with hereditary cyclo-oxygenase deficiency, contraction produced by thrombin at low concentration (0.02 UI/ml) failed to induce contraction.", "contents": "[Sterologic evaluation on in vitro thrombin-induced platelet degranulation and contraction (author's transl)]. Stereologic study of the in vitro release reaction from unstirred washed platelets provided quantitative information on the contractile wave induced by thrombin. Contraction was estimated from the reduction in the volume of both the granular compartment and the vacuoles of the surface connected canalicular system. Dibutyryl cyclic-AMP (10(-4) M) and dipyridamole (10(-3) M) inhibited degranulation, but they had no effect on the contraction produced by thrombin at high concentrations (0.1 UI/ml). Aspirin (10(-4) M) inhibited contraction induced by thrombin at concentration of 0.1 and 0.02 UI/ml (p less than 0.01 at each concentration). In two patients with hereditary cyclo-oxygenase deficiency, contraction produced by thrombin at low concentration (0.02 UI/ml) failed to induce contraction."}
{"id": "PMID:212714", "title": "Characterization of two SV40 early mRNAs and evidence for a nuclear \"prespliced\" RNA species.", "content": "Using in vitro translation of sucrose-gradient fractionated cytoplasmic mRNA from SV40-infected cells, we have shown that a deletion in the region mapping between 0.54--0.59 reduced the size of mRNA for small-t but not the size of mRNA for large-T. Mutants with a deletion in this region were shown to produce in vivo either shortened small-t or no small-t, and normal large-T. Similarly, in vitro translation of poly(A)+cytoplasmic RNA from cells infected with these mutants gave the same results. On the other hand in vitro translation of poly(A)+nuclear RNA from the mutants which made no small-t produced a small-t derivative possibly synthesized from a prespliced RNA species. We have also shown that poly(A)+nuclear RNA from mutant dl 2122 produced two small-t related proteins: one of these (MW: 11K) probably represents the product of a \"prespliced\" RNA, the other (MW: 17K) which is also found in the cytoplasm represents the product of the mutant specific small-t mRNA.", "contents": "Characterization of two SV40 early mRNAs and evidence for a nuclear \"prespliced\" RNA species. Using in vitro translation of sucrose-gradient fractionated cytoplasmic mRNA from SV40-infected cells, we have shown that a deletion in the region mapping between 0.54--0.59 reduced the size of mRNA for small-t but not the size of mRNA for large-T. Mutants with a deletion in this region were shown to produce in vivo either shortened small-t or no small-t, and normal large-T. Similarly, in vitro translation of poly(A)+cytoplasmic RNA from cells infected with these mutants gave the same results. On the other hand in vitro translation of poly(A)+nuclear RNA from the mutants which made no small-t produced a small-t derivative possibly synthesized from a prespliced RNA species. We have also shown that poly(A)+nuclear RNA from mutant dl 2122 produced two small-t related proteins: one of these (MW: 11K) probably represents the product of a \"prespliced\" RNA, the other (MW: 17K) which is also found in the cytoplasm represents the product of the mutant specific small-t mRNA."}
{"id": "PMID:212715", "title": "DNAse footprinting: a simple method for the detection of protein-DNA binding specificity.", "content": "A method for studying the sequence-specific binding of proteins to DBA is described. The technique is a simple conjoining of the Maxam-Gilbert DNA-sequencing method and the technique of DNAase-protected fragment isolation. Fragments of a 5' end-labelled, double-stranded DNA segment, partially degraded by DNAase in the presence and absence of the binding protein, are visualized by electrophoresis and autoradiography alongside the base-specific reaction products of the Maxam-Gilbert sequencing method. It is then possible to see the protective \"footprint\" of the binding protein on the DNA sequence. The binding of lac repressor to lac operator is visualized by \"footprinting\" as an example. Equillibrium estimates indicate that 10-fold sequence-specificity (differential binding constant) could be studied easily using this technique.", "contents": "DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. A method for studying the sequence-specific binding of proteins to DBA is described. The technique is a simple conjoining of the Maxam-Gilbert DNA-sequencing method and the technique of DNAase-protected fragment isolation. Fragments of a 5' end-labelled, double-stranded DNA segment, partially degraded by DNAase in the presence and absence of the binding protein, are visualized by electrophoresis and autoradiography alongside the base-specific reaction products of the Maxam-Gilbert sequencing method. It is then possible to see the protective \"footprint\" of the binding protein on the DNA sequence. The binding of lac repressor to lac operator is visualized by \"footprinting\" as an example. Equillibrium estimates indicate that 10-fold sequence-specificity (differential binding constant) could be studied easily using this technique."}
{"id": "PMID:212716", "title": "Requirement for 7-methylguanosine in translation of globin mRNA in vivo.", "content": "The 7-methylguanosine (m7G) residue present in the m7G5' ppp5'X-\"CAP\" structure of rabbit globin mRNA was removed quantitatively by periodate oxidation followed by beta-elimination in the presence of cyclohexylamine. The RNA thus treated was intact and exhibited no signs of degradation as examined by polyacrylamide gel electrophoresis in formamide. Assay for protein synthesis using a wheat germ cell-free system showed that the globin mRNA lacking m7G had lost most of its messenger activity. Identical treatment, of satellite tobacco necrosis virus (STNV) RNA, which does not contain the 5'-terminal \"CAP\" structure, resulted in no loss of its mRNA activity. Since the importance of the m7G residue in eukaryotic mRNA has not yet been shown essential for translation in vivo, both untreated and treated globin mRNAs were injected into frog oocytes and their translation into globin was measured at intervals over a ninety-six hour period. Globin mRNA either treated with periodate alone or lacking in m7g altogether were both found to have lost more than 90% of their activity in vivo.", "contents": "Requirement for 7-methylguanosine in translation of globin mRNA in vivo. The 7-methylguanosine (m7G) residue present in the m7G5' ppp5'X-\"CAP\" structure of rabbit globin mRNA was removed quantitatively by periodate oxidation followed by beta-elimination in the presence of cyclohexylamine. The RNA thus treated was intact and exhibited no signs of degradation as examined by polyacrylamide gel electrophoresis in formamide. Assay for protein synthesis using a wheat germ cell-free system showed that the globin mRNA lacking m7G had lost most of its messenger activity. Identical treatment, of satellite tobacco necrosis virus (STNV) RNA, which does not contain the 5'-terminal \"CAP\" structure, resulted in no loss of its mRNA activity. Since the importance of the m7G residue in eukaryotic mRNA has not yet been shown essential for translation in vivo, both untreated and treated globin mRNAs were injected into frog oocytes and their translation into globin was measured at intervals over a ninety-six hour period. Globin mRNA either treated with periodate alone or lacking in m7g altogether were both found to have lost more than 90% of their activity in vivo."}
{"id": "PMID:212726", "title": "Sexually transmitted diseases. Advances in management.", "content": "We have briefly presented practical approaches to the management of the most common disorders caused by sexually transmitted pathogens, including pelvic inflammatory disease, urethritis in men, genital lesions, vaginal discharge, and syphilis. Guidelines for the management of gonorrhea may change if penicillin-resistant strains become more prevalent. Areas which require further research include the treatment of genital herpes and the prevention of recurrences, the treatment of nonspecific vaginitis, and definition of the importance of metronidazole toxicity.", "contents": "Sexually transmitted diseases. Advances in management. We have briefly presented practical approaches to the management of the most common disorders caused by sexually transmitted pathogens, including pelvic inflammatory disease, urethritis in men, genital lesions, vaginal discharge, and syphilis. Guidelines for the management of gonorrhea may change if penicillin-resistant strains become more prevalent. Areas which require further research include the treatment of genital herpes and the prevention of recurrences, the treatment of nonspecific vaginitis, and definition of the importance of metronidazole toxicity."}
{"id": "PMID:212727", "title": "Special investigations in COCM: biochemical analysis of cardiac biopsies.", "content": "The introduction of the endomyocardial biopsy method has permitted unique possibilities to investigate the myocardium. Compared to several other methods described, it is superior for taking serial biopsies on one or more occasions. With already available methods, examination of heart muscle biopsies can be extended to a wide variety of biochemical analyses. The ultimate application of repeated or periodic tissue sampling is the potential of combining static and dynamic studies.", "contents": "Special investigations in COCM: biochemical analysis of cardiac biopsies. The introduction of the endomyocardial biopsy method has permitted unique possibilities to investigate the myocardium. Compared to several other methods described, it is superior for taking serial biopsies on one or more occasions. With already available methods, examination of heart muscle biopsies can be extended to a wide variety of biochemical analyses. The ultimate application of repeated or periodic tissue sampling is the potential of combining static and dynamic studies."}
{"id": "PMID:212731", "title": "Coordination environment and fluoride binding of type 2 copper in the blue copper oxidase ceruloplasmin.", "content": "The electron paramagnetic resonance (EPR) spectra of the blue copper oxidase ceruloplasmin [ferroxidase, iron (II):oxygen oxidoreductase, EC 1.16.3.1] and of a derivative having the type I (blue) copper centers reversibly bleached are reported. The EPR spectrum of bleached ceruloplasmin has a seven-line superhyperfine structure in the g : formula: (see text) region that is attributed to the presence of three nitrogen-donor type 2 copper ligands. The EPR data suggest further that the type 2 copper in ceruloplasmin possesses a tetragonal coordination gometry. In the presence of varying amounts of fluoride, superhyperfine splitting patterns in the g : formula: (see text) region of both ceruloplasmin derivatives indicate that a maximum of two fluorides may be bound to the type 2 copper.", "contents": "Coordination environment and fluoride binding of type 2 copper in the blue copper oxidase ceruloplasmin. The electron paramagnetic resonance (EPR) spectra of the blue copper oxidase ceruloplasmin [ferroxidase, iron (II):oxygen oxidoreductase, EC 1.16.3.1] and of a derivative having the type I (blue) copper centers reversibly bleached are reported. The EPR spectrum of bleached ceruloplasmin has a seven-line superhyperfine structure in the g : formula: (see text) region that is attributed to the presence of three nitrogen-donor type 2 copper ligands. The EPR data suggest further that the type 2 copper in ceruloplasmin possesses a tetragonal coordination gometry. In the presence of varying amounts of fluoride, superhyperfine splitting patterns in the g : formula: (see text) region of both ceruloplasmin derivatives indicate that a maximum of two fluorides may be bound to the type 2 copper."}
{"id": "PMID:212729", "title": "[Obtaining iodinated luteinizing hormone while preserving its biological properties].", "content": "The author describes a method of obtaining biologically-active 125I-labeled luteinzing hormone in iodation with chloramine T. The hormone and chloramine T concentration ratio of 1:2, and the reaction time of 20 sec was used. LH-125I with the specific activity of 27--30 microCi/microgram was bound with the receptor strictly specifically.", "contents": "[Obtaining iodinated luteinizing hormone while preserving its biological properties]. The author describes a method of obtaining biologically-active 125I-labeled luteinzing hormone in iodation with chloramine T. The hormone and chloramine T concentration ratio of 1:2, and the reaction time of 20 sec was used. LH-125I with the specific activity of 27--30 microCi/microgram was bound with the receptor strictly specifically."}
{"id": "PMID:212732", "title": "DNA modifying enzymes of Agrobacterium tumefaciens: effect of DNA topoisomerase, restriction endonuclease, and unique DNA endonuclease on plasmid and plant DNA.", "content": "Extracts from Agrobacterium tumefaciens strain ID135 contain three enzymes that have been characterized and partially purified. The first enzyme, a DNA topoisomerase, appeared to relax only negatively twisted DNA. The second enzyme, Atu I, a type II restriction endonuclease, generated the identical DNA digestion pattern as EcoRII when several DNAs were used. The third enzyme, endonuclease A, showed a preference for superhelical DNAs as substrates. When plasmid pCK135DNA, obtained from the virulent strain IDI135 of A. tumefaciens, or plant DNA was exposed to the three enzymes, changes in DNA patterns were observed due to either conformational changes or digestion of the DNAs. These enzymes may function in vivo in the processing and incorporation of bacterial DNA in plant cells.", "contents": "DNA modifying enzymes of Agrobacterium tumefaciens: effect of DNA topoisomerase, restriction endonuclease, and unique DNA endonuclease on plasmid and plant DNA. Extracts from Agrobacterium tumefaciens strain ID135 contain three enzymes that have been characterized and partially purified. The first enzyme, a DNA topoisomerase, appeared to relax only negatively twisted DNA. The second enzyme, Atu I, a type II restriction endonuclease, generated the identical DNA digestion pattern as EcoRII when several DNAs were used. The third enzyme, endonuclease A, showed a preference for superhelical DNAs as substrates. When plasmid pCK135DNA, obtained from the virulent strain IDI135 of A. tumefaciens, or plant DNA was exposed to the three enzymes, changes in DNA patterns were observed due to either conformational changes or digestion of the DNAs. These enzymes may function in vivo in the processing and incorporation of bacterial DNA in plant cells."}
{"id": "PMID:212733", "title": "Nucleotide sequences related to the transforming gene of avian sarcoma virus are present in DNA of uninfected vertebrates.", "content": "We have detected nucleotide sequences related to the transforming gene of avian sarcoma vius (ASV) in the DNA of uninfected vertebrates. Purified radioactive DNA (cDNAsarc) complementary to most of all of the gene (src) required for transformation of fibroblasts by ASV was annealed with DNA from a variety of normal species. Under conditions that facilitate pairing of partially matched nucleotide sequences (1.5 M NaCl, 59 degrees), cDNAsarc formed duplexes with chicken, human, calf, mouse, and salmon DNA but not with DNA from sea urchin, Drosophila, or Escherichia coli. The kinetics of duplex formation indicated that cDNAsarc was reacting with nucleotide sequences present in a single copy or at most a few copies per cell. In contrast to the preceding findings, nucleotide sequences complementary to the remainder of the ASV genome were observed only in chicken DNA. Thermal denaturation studies of the duplexes formed with cDNAsarc indicated a high degree of conservation of the nucleotide sequences related to src in vertebrate DNAs; the reductions in melting temperature suggested about 3--4% mismatching of cDNAsarc with chicken DNA and 8--10% mismatching of cDNAsarc with the other vertebrate DNAs.", "contents": "Nucleotide sequences related to the transforming gene of avian sarcoma virus are present in DNA of uninfected vertebrates. We have detected nucleotide sequences related to the transforming gene of avian sarcoma vius (ASV) in the DNA of uninfected vertebrates. Purified radioactive DNA (cDNAsarc) complementary to most of all of the gene (src) required for transformation of fibroblasts by ASV was annealed with DNA from a variety of normal species. Under conditions that facilitate pairing of partially matched nucleotide sequences (1.5 M NaCl, 59 degrees), cDNAsarc formed duplexes with chicken, human, calf, mouse, and salmon DNA but not with DNA from sea urchin, Drosophila, or Escherichia coli. The kinetics of duplex formation indicated that cDNAsarc was reacting with nucleotide sequences present in a single copy or at most a few copies per cell. In contrast to the preceding findings, nucleotide sequences complementary to the remainder of the ASV genome were observed only in chicken DNA. Thermal denaturation studies of the duplexes formed with cDNAsarc indicated a high degree of conservation of the nucleotide sequences related to src in vertebrate DNAs; the reductions in melting temperature suggested about 3--4% mismatching of cDNAsarc with chicken DNA and 8--10% mismatching of cDNAsarc with the other vertebrate DNAs."}
{"id": "PMID:212734", "title": "Antagonists of DNA gyrase inhibit repair and recombination of UV-irradiated phage lambda.", "content": "Intracellular lambda DNA (from EDTA-sensitive tandem duplication phages) was extracted from infected rec+ bacteria and scored for infectivity and recombination (loss of duplication) by transfection of recA recB spheroplasts and subsequent assay for EDTA resistance. When phage development was blocked by repressor or by antibiotics (chloramphenicol and/or rifampin), the apparent recombination frequency was about 0.1% above the background value for recA infections. Prior irradiation of the phage greatly stimulated recombination; the frequency was 20% when UV fluence was 140 J/m2. Repair (recovery of infectivity) and recombination of irradiated phage DNA proceeded readily in the presence of chloramphenicol and rifampin. Inhibitors of DNA gyrase (coumermycin and oxolinic acid) blocked repair and reduced recombination. UV-stimulated recombination was very low in recA but nearly normal in recB cells: repair was reduced in both mutant strains. The recombination remained high as phage/cell ratios less than unity.", "contents": "Antagonists of DNA gyrase inhibit repair and recombination of UV-irradiated phage lambda. Intracellular lambda DNA (from EDTA-sensitive tandem duplication phages) was extracted from infected rec+ bacteria and scored for infectivity and recombination (loss of duplication) by transfection of recA recB spheroplasts and subsequent assay for EDTA resistance. When phage development was blocked by repressor or by antibiotics (chloramphenicol and/or rifampin), the apparent recombination frequency was about 0.1% above the background value for recA infections. Prior irradiation of the phage greatly stimulated recombination; the frequency was 20% when UV fluence was 140 J/m2. Repair (recovery of infectivity) and recombination of irradiated phage DNA proceeded readily in the presence of chloramphenicol and rifampin. Inhibitors of DNA gyrase (coumermycin and oxolinic acid) blocked repair and reduced recombination. UV-stimulated recombination was very low in recA but nearly normal in recB cells: repair was reduced in both mutant strains. The recombination remained high as phage/cell ratios less than unity."}
{"id": "PMID:212735", "title": "Alterations of hepatic Na+,K+-atpase and bile flow by estrogen: effects on liver surface membrane lipid structure and function.", "content": "Administration of the synthetic estrogen ethinyl estradiol (17alpha-ethinyl-1,3,5-estratriene-3,17beta-diol) decreases hepatic Na(+),K(+)-ATPase (ATP phosphohydrolase; EC 3.6.1.3) activity and bile flow to 50% and alters the composition and structure of surface membrane lipid in rats. Although the content of phospholipids was not changed by treatment, free cholesterol (130%) and cholesterol esters (400%) were increased in liver surface membrane fractions. These observations correlate with changes in membrane viscosity, as shown by electron spin resonance probes. Both rotational correlation time, using the isotropic probe methyl (12-nitroxyl)stearate, and the order parameter, determined by the anisotropic probe 5-nitroxylstearic acid, were significantly increased in liver surface membrane fractions from rats treated with ethinyl estradiol. Administration of Triton WR-1339, a nonionic detergent that corrects hepatic and serum lipid changes caused by ethinyl estradiol treatment, restored toward normal elevated membrane lipids and viscosity as well as Na(+),K(+)-ATPase activity and bile flow. Although restoration of normal liver surface membrane structure and function may be due to reversal of abnormal lipid composition, detergents also may directly alter membrane enzyme activity. Addition of Triton WR-1339 in vitro increased Na(+),K(+)-ATPase activity and reduced membrane viscosity of surface membranes from rats treated with ethinyl estradiol. Triton had no effect on either parameter in normal membrane preparations. Studies of membrane structure and function both in vivo and in vitro suggest that alterations in lipid composition may alter Na(+),K(+)-ATPase function and bile flow.", "contents": "Alterations of hepatic Na+,K+-atpase and bile flow by estrogen: effects on liver surface membrane lipid structure and function. Administration of the synthetic estrogen ethinyl estradiol (17alpha-ethinyl-1,3,5-estratriene-3,17beta-diol) decreases hepatic Na(+),K(+)-ATPase (ATP phosphohydrolase; EC 3.6.1.3) activity and bile flow to 50% and alters the composition and structure of surface membrane lipid in rats. Although the content of phospholipids was not changed by treatment, free cholesterol (130%) and cholesterol esters (400%) were increased in liver surface membrane fractions. These observations correlate with changes in membrane viscosity, as shown by electron spin resonance probes. Both rotational correlation time, using the isotropic probe methyl (12-nitroxyl)stearate, and the order parameter, determined by the anisotropic probe 5-nitroxylstearic acid, were significantly increased in liver surface membrane fractions from rats treated with ethinyl estradiol. Administration of Triton WR-1339, a nonionic detergent that corrects hepatic and serum lipid changes caused by ethinyl estradiol treatment, restored toward normal elevated membrane lipids and viscosity as well as Na(+),K(+)-ATPase activity and bile flow. Although restoration of normal liver surface membrane structure and function may be due to reversal of abnormal lipid composition, detergents also may directly alter membrane enzyme activity. Addition of Triton WR-1339 in vitro increased Na(+),K(+)-ATPase activity and reduced membrane viscosity of surface membranes from rats treated with ethinyl estradiol. Triton had no effect on either parameter in normal membrane preparations. Studies of membrane structure and function both in vivo and in vitro suggest that alterations in lipid composition may alter Na(+),K(+)-ATPase function and bile flow."}
{"id": "PMID:212736", "title": "6-beta-bromopenicillanic acid, a potent beta-lactamase inhibitor.", "content": "6-beta-Bromopenicillanic acid, which arises from the epimerization of 6-alpha-bromopenicillanic acid in aqueous solution or from hydrogenation of 6,6-dibromopenicillanic acid, is a powerful, irreversible, active-site-directed inhibitor of several typical beta-lactamases (penicillinase; penicillin amido-beta-lactamhydrolase, EC 3.5.2.6); 6-alpha-bromopenicillanic acid, being completely inhibited at less than micromolar concentrations through what is probably a 1:1 interaction. The B. licheniformis exoenzyme is similarly susceptible, while the Staphylococcus aureus enzyme and the Escherichia coli (R factor) enzyme are less so; the B. cereus beta-lactamase II is not inhibited. Very high concentrations (greater than or equal to 0.1 M) of benzylpenicillin, a good substrate, are required to significantly reduce the rate of inhibition of B. cereus beta-lactamase I by 6-beta-bromopenicillanic acid.", "contents": "6-beta-bromopenicillanic acid, a potent beta-lactamase inhibitor. 6-beta-Bromopenicillanic acid, which arises from the epimerization of 6-alpha-bromopenicillanic acid in aqueous solution or from hydrogenation of 6,6-dibromopenicillanic acid, is a powerful, irreversible, active-site-directed inhibitor of several typical beta-lactamases (penicillinase; penicillin amido-beta-lactamhydrolase, EC 3.5.2.6); 6-alpha-bromopenicillanic acid, being completely inhibited at less than micromolar concentrations through what is probably a 1:1 interaction. The B. licheniformis exoenzyme is similarly susceptible, while the Staphylococcus aureus enzyme and the Escherichia coli (R factor) enzyme are less so; the B. cereus beta-lactamase II is not inhibited. Very high concentrations (greater than or equal to 0.1 M) of benzylpenicillin, a good substrate, are required to significantly reduce the rate of inhibition of B. cereus beta-lactamase I by 6-beta-bromopenicillanic acid."}
{"id": "PMID:212737", "title": "Mechanism of adenylate cyclase activation through the beta-adrenergic receptor: catecholamine-induced displacement of bound GDP by GTP.", "content": "The fate of the guanyl nucleotide bound to the regulatory site of adenylate cyclase was studied on a preparation of turkey erythrocyte membranes that was incubated with [3H]GTP plus isoproterenol and subsequently washed to remove hormone and free guanyl nucleotide. Further incubation of this preparation in the presence of beta-adrenergic agonists resulted in the release from the membrane of tritiated nucleotide, identified as [3H]GDP. The catecholamine-induced release of [3H]GDP was increased 2 to 3 times in the presence of the unlabeled guanyl nucleotides GTP, guanosine 5'-(beta,gamma-imino)triphosphate [gpp(NH)p], GDP, and GMP, whereas adenine nucleotides had little effect. In the presence of Gpp(NH)p, isoproterenol induced the release of [3H]GDP and the activation of adenylate cyclase, both effects following similar time courses. The findings indicate that the inactive adenylate cyclase possesses tightly bound (GDP, produced by the hydrolysis of GTP at the regulatory site. The hormone stimulates adenylate cyclase activity by inducing an \"opening\" of the guanyl nucleotide site, resulting in dissociation of the bound GDP and binding of the activating guanosine triphosphate.", "contents": "Mechanism of adenylate cyclase activation through the beta-adrenergic receptor: catecholamine-induced displacement of bound GDP by GTP. The fate of the guanyl nucleotide bound to the regulatory site of adenylate cyclase was studied on a preparation of turkey erythrocyte membranes that was incubated with [3H]GTP plus isoproterenol and subsequently washed to remove hormone and free guanyl nucleotide. Further incubation of this preparation in the presence of beta-adrenergic agonists resulted in the release from the membrane of tritiated nucleotide, identified as [3H]GDP. The catecholamine-induced release of [3H]GDP was increased 2 to 3 times in the presence of the unlabeled guanyl nucleotides GTP, guanosine 5'-(beta,gamma-imino)triphosphate [gpp(NH)p], GDP, and GMP, whereas adenine nucleotides had little effect. In the presence of Gpp(NH)p, isoproterenol induced the release of [3H]GDP and the activation of adenylate cyclase, both effects following similar time courses. The findings indicate that the inactive adenylate cyclase possesses tightly bound (GDP, produced by the hydrolysis of GTP at the regulatory site. The hormone stimulates adenylate cyclase activity by inducing an \"opening\" of the guanyl nucleotide site, resulting in dissociation of the bound GDP and binding of the activating guanosine triphosphate."}
{"id": "PMID:212738", "title": "Structural markers on core protein p30 of murine leukemia virus: functional correlation with Fv-1 tropism.", "content": "Tryptic peptide maps from more than 50 isolates of murine leukemia virus (MuLV) have shown that, in general, the structure of core protein p30 is highly conserved. However, a structurally variable region of p30 has been identified that is functionally associated with Fv-1 tropism. On the basis of this structural variability, MuLV strains can be classified as B-tropic, N-tropic, xenotropic, and/or as being derived from wild mice. Certain xenotropic viruses have a p30 like that of B-tropic MuLV and presumably would be subject to restriction in cells containing an Fv-In allele. Other p30 structural markers serve to distinguish the exogenous Friend, Moloney, and Rauscher viruses from endogenous MuLV. Furthermore, some MuLV strains have structural differences in their p30s that are useful as strain-specific markers. Finally, a possible sarcoma-associated alteration in the structure of p30 has been noted in the ml clone of Moloney murine sarcoma virus.", "contents": "Structural markers on core protein p30 of murine leukemia virus: functional correlation with Fv-1 tropism. Tryptic peptide maps from more than 50 isolates of murine leukemia virus (MuLV) have shown that, in general, the structure of core protein p30 is highly conserved. However, a structurally variable region of p30 has been identified that is functionally associated with Fv-1 tropism. On the basis of this structural variability, MuLV strains can be classified as B-tropic, N-tropic, xenotropic, and/or as being derived from wild mice. Certain xenotropic viruses have a p30 like that of B-tropic MuLV and presumably would be subject to restriction in cells containing an Fv-In allele. Other p30 structural markers serve to distinguish the exogenous Friend, Moloney, and Rauscher viruses from endogenous MuLV. Furthermore, some MuLV strains have structural differences in their p30s that are useful as strain-specific markers. Finally, a possible sarcoma-associated alteration in the structure of p30 has been noted in the ml clone of Moloney murine sarcoma virus."}
{"id": "PMID:212739", "title": "Mechanism of the in vitro breakdown of guanosine 5'-diphosphate 3'-diphosphate in Escherichia coli.", "content": "Degradation of guanosine tetraphosphate (ppGpp) involves an enzyme associated with the ribosomal fraction from spoT+ strains of Escherichia coli. Double-label experiments with pp[3h]gpp, pp[3H]Gpp, or pp[3H]Gpp as substrate strongly suggest that ppG is the degradation product and that the enzyme releases two phosphates coordinately from the 3' position of ppGpp. In the absence of pppA this reaction proceeds in an uncoupled fashion, yielding ppG and PPi, but in the presence of pppA the decay is considerably enhanced and a pppA-ppi exchange reaction occurs in which the 3'-pyrophosphoryl group of ppGpp displaces the gamma and beta phosphates of pppA. Sodium PPi at 4 m7 inhibits decay of ppGpp regardless of whether or not pppA is present.", "contents": "Mechanism of the in vitro breakdown of guanosine 5'-diphosphate 3'-diphosphate in Escherichia coli. Degradation of guanosine tetraphosphate (ppGpp) involves an enzyme associated with the ribosomal fraction from spoT+ strains of Escherichia coli. Double-label experiments with pp[3h]gpp, pp[3H]Gpp, or pp[3H]Gpp as substrate strongly suggest that ppG is the degradation product and that the enzyme releases two phosphates coordinately from the 3' position of ppGpp. In the absence of pppA this reaction proceeds in an uncoupled fashion, yielding ppG and PPi, but in the presence of pppA the decay is considerably enhanced and a pppA-ppi exchange reaction occurs in which the 3'-pyrophosphoryl group of ppGpp displaces the gamma and beta phosphates of pppA. Sodium PPi at 4 m7 inhibits decay of ppGpp regardless of whether or not pppA is present."}
{"id": "PMID:212740", "title": "Changes in hepatic messenger RNA for phosphoenolpyruvate carboxykinase (GTP) during development.", "content": "Phosphoenolpyruvate carboxykinase (GTP) [GTP;oxaloacetate carboxy-lyase(transphosphorylating); EC 4.1.1.32] is absent in rat liver cytosol during fetal life and is synthesized initially at birth. De novo synthesis of the enzyme can be induced prematurely by injection of dibutyryl cyclic AMP or glucagon into fetal animals in utero. In this study a wheat germ translation assay was used to quantitate the level of total functional mRNA for phosphoenolpyruvate carboxykinase in the liver of fetal rats at 21 days of pregnancy under different induction situations. The translatable mRNA for the enzyme was marginally detectable in fetal rat liver. Administration of either glucagon or dibutyryl cyclic AMP to fetal rats in utero caused a marked induction of functional mRNA for this enzyme. Three hours after administration of dibutyryl cyclic AMP, the level of translatable mRNA increased almost 23-fold, but by 6 hr the level dropped approximately 60%. Administration of actinomycin D prior to dibutyryl cyclic AMP in 21-day fetal rats prevented the appearance of newly synthesized poly(A)-containing RNA in the cytoplasm as well as the induction of translatable mRNA for phosphoenolpyruvate carboxykinase. In animals delivered prematurely and maintained for varying periods, the translatable mRNA for the enzyme accumulated in the liver at a rate comparable to that observed for enzyme synthesis.", "contents": "Changes in hepatic messenger RNA for phosphoenolpyruvate carboxykinase (GTP) during development. Phosphoenolpyruvate carboxykinase (GTP) [GTP;oxaloacetate carboxy-lyase(transphosphorylating); EC 4.1.1.32] is absent in rat liver cytosol during fetal life and is synthesized initially at birth. De novo synthesis of the enzyme can be induced prematurely by injection of dibutyryl cyclic AMP or glucagon into fetal animals in utero. In this study a wheat germ translation assay was used to quantitate the level of total functional mRNA for phosphoenolpyruvate carboxykinase in the liver of fetal rats at 21 days of pregnancy under different induction situations. The translatable mRNA for the enzyme was marginally detectable in fetal rat liver. Administration of either glucagon or dibutyryl cyclic AMP to fetal rats in utero caused a marked induction of functional mRNA for this enzyme. Three hours after administration of dibutyryl cyclic AMP, the level of translatable mRNA increased almost 23-fold, but by 6 hr the level dropped approximately 60%. Administration of actinomycin D prior to dibutyryl cyclic AMP in 21-day fetal rats prevented the appearance of newly synthesized poly(A)-containing RNA in the cytoplasm as well as the induction of translatable mRNA for phosphoenolpyruvate carboxykinase. In animals delivered prematurely and maintained for varying periods, the translatable mRNA for the enzyme accumulated in the liver at a rate comparable to that observed for enzyme synthesis."}
{"id": "PMID:212741", "title": "Transfer of duck cell DNA sequences to the nucleus of 3T3 cells by Rous sarcoma virus.", "content": "Peking duck cell nuclear DNA has no complementarity to RNA of Prague C Rous sarcoma virus (RSV). Upon infection of Peking duck cells by Prague C RSV, polynucleotide sequences complementary to Peking duck cell nuclear DNA can be detected in the high molecular weight RNA from progeny Peking duck cell passaged RSV (RSVPD) by RNA.DNA molecular hybridazation. When 3T3 cells are subsequently infected by RSVPD, polynucleotide sequences complementary to Peking duck cell nuclear DNA can be detected in the 3T3 cell nuclear DNA by RNA.DNA molecular hybridization. The potential consequences of the transfer of the Peking duck cell nuclear DNA from the avian to the murine cells are discussed.", "contents": "Transfer of duck cell DNA sequences to the nucleus of 3T3 cells by Rous sarcoma virus. Peking duck cell nuclear DNA has no complementarity to RNA of Prague C Rous sarcoma virus (RSV). Upon infection of Peking duck cells by Prague C RSV, polynucleotide sequences complementary to Peking duck cell nuclear DNA can be detected in the high molecular weight RNA from progeny Peking duck cell passaged RSV (RSVPD) by RNA.DNA molecular hybridazation. When 3T3 cells are subsequently infected by RSVPD, polynucleotide sequences complementary to Peking duck cell nuclear DNA can be detected in the 3T3 cell nuclear DNA by RNA.DNA molecular hybridization. The potential consequences of the transfer of the Peking duck cell nuclear DNA from the avian to the murine cells are discussed."}
{"id": "PMID:212742", "title": "Temperature-sensitive replication of H5ts125 adenovirus DNA in vitro.", "content": "A soluble adenovirus DNA replication system has been prepared in extracts of HeLa cells infected with the temperature-sensitive mutant H5ts125. These nuclear extracts synthesize full-sized viral DNA at 30 degrees but are temperature sensitive in this function at 38 degrees. A 72,000-dalton DNA-binding protein purified from cells infected with wild-type virus complements the temperature-sensitive defect and restores viral DNA replication to 74% of normal values.", "contents": "Temperature-sensitive replication of H5ts125 adenovirus DNA in vitro. A soluble adenovirus DNA replication system has been prepared in extracts of HeLa cells infected with the temperature-sensitive mutant H5ts125. These nuclear extracts synthesize full-sized viral DNA at 30 degrees but are temperature sensitive in this function at 38 degrees. A 72,000-dalton DNA-binding protein purified from cells infected with wild-type virus complements the temperature-sensitive defect and restores viral DNA replication to 74% of normal values."}
{"id": "PMID:212743", "title": "Inhibition of mammalian protein kinase and phosphodiesterase activities by a cyclic AMP-like compound isolated from higher plants.", "content": "A cyclic AMP-like substance has been isolated from higher plant tissues which can be quantitated with the use of a radioimmunoassay similar to that described by A. L. Steiner, D. M. Kipnis, R. Utiger, and C. Parker [(1969) Proc. Natl. Acad. Sci. USA 64, 367-373]. This compound has been extensively purified and is chromatographically distinct from authentic cyclic AMP. This cyclic AMP-like compound inhibited beef heart 3':5'-cyclic-nucleotide phosphodietsterase (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17), with half-maximal inhibition occurring at a concentration of 7.6 X 10(-10) M cyclic AMP equivalents. The compound also inhibited cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase; EC 2.7.1.37) from bovine heart, with half-maximal inhibition of mixed histone phosphorylation occurring at 8.0 X 10(-11) M cyclic AMP equivalents. Equipotent inhibition of phosphorylation and associated trace ATPase activity were observed with the purified catalytic subunit of cyclic AMP-dependent protein kinase from calf thymus with a synthetic heptapeptide as substrate. Moreover, steady-state kinetic analysis of this inhibition in the latter system showed it to be nonlinear and noncompetitive versus MgATP.", "contents": "Inhibition of mammalian protein kinase and phosphodiesterase activities by a cyclic AMP-like compound isolated from higher plants. A cyclic AMP-like substance has been isolated from higher plant tissues which can be quantitated with the use of a radioimmunoassay similar to that described by A. L. Steiner, D. M. Kipnis, R. Utiger, and C. Parker [(1969) Proc. Natl. Acad. Sci. USA 64, 367-373]. This compound has been extensively purified and is chromatographically distinct from authentic cyclic AMP. This cyclic AMP-like compound inhibited beef heart 3':5'-cyclic-nucleotide phosphodietsterase (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17), with half-maximal inhibition occurring at a concentration of 7.6 X 10(-10) M cyclic AMP equivalents. The compound also inhibited cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase; EC 2.7.1.37) from bovine heart, with half-maximal inhibition of mixed histone phosphorylation occurring at 8.0 X 10(-11) M cyclic AMP equivalents. Equipotent inhibition of phosphorylation and associated trace ATPase activity were observed with the purified catalytic subunit of cyclic AMP-dependent protein kinase from calf thymus with a synthetic heptapeptide as substrate. Moreover, steady-state kinetic analysis of this inhibition in the latter system showed it to be nonlinear and noncompetitive versus MgATP."}
{"id": "PMID:212744", "title": "Isolation, characterization, and synthesis of a corticotropin-inhibiting peptide from human pituitary glands.", "content": "A corticotropin-inhibiting peptide (CIP) has been isolated from human pituitary extracts. It consists of 32 amino acids with a proposed sequence identical to residues 7--38 of corticotropin (ACTH). The peptide has been synthesized by the solid-phase method. The melanotropic activity of the peptide is estimated to be 30% of the potency of ACTH. It is devoid of corticosteroidogenic activity but is able to inhibit ACTH-stimulated corticosterone production in isolated rat adrenal cells.", "contents": "Isolation, characterization, and synthesis of a corticotropin-inhibiting peptide from human pituitary glands. A corticotropin-inhibiting peptide (CIP) has been isolated from human pituitary extracts. It consists of 32 amino acids with a proposed sequence identical to residues 7--38 of corticotropin (ACTH). The peptide has been synthesized by the solid-phase method. The melanotropic activity of the peptide is estimated to be 30% of the potency of ACTH. It is devoid of corticosteroidogenic activity but is able to inhibit ACTH-stimulated corticosterone production in isolated rat adrenal cells."}
{"id": "PMID:212745", "title": "Immobilized lipid in acetylcholine receptor-rich membranes from Torpedo marmorata.", "content": "The lipid environment of acetylcholine receptor-rich membranes from Torpedo marmorata has been studied with spin labels. The electron spin resonance spectra of both stearic acid and steroid probes in the membranes revealed an immobilized lipid component, in addition to the fluid component which is found in aqueous bilayer dispersions of the extracted lipids. The spin labels also cause a differential paramagnetic quenching of the intrinsic protein fluorescence of the membranes, which is sensitive to the action of cholinergic ligands and follows a modified Stern-Volmer law. Electron spin resonance difference spectroscopy shows that the protein-associated lipid is immobilized with respect to rotation both around and perpendicular to the long molecular axis, with correlation times : formula: (see text) approximately 50-70 ns. The proportion of lipid in the immobilized component is greater than calculated for a single boundary layer around the protein and corresponds more closely to the total interstitial lipid occupying the area between densely packed protein units in acetylcholine receptor-rich membranes.", "contents": "Immobilized lipid in acetylcholine receptor-rich membranes from Torpedo marmorata. The lipid environment of acetylcholine receptor-rich membranes from Torpedo marmorata has been studied with spin labels. The electron spin resonance spectra of both stearic acid and steroid probes in the membranes revealed an immobilized lipid component, in addition to the fluid component which is found in aqueous bilayer dispersions of the extracted lipids. The spin labels also cause a differential paramagnetic quenching of the intrinsic protein fluorescence of the membranes, which is sensitive to the action of cholinergic ligands and follows a modified Stern-Volmer law. Electron spin resonance difference spectroscopy shows that the protein-associated lipid is immobilized with respect to rotation both around and perpendicular to the long molecular axis, with correlation times : formula: (see text) approximately 50-70 ns. The proportion of lipid in the immobilized component is greater than calculated for a single boundary layer around the protein and corresponds more closely to the total interstitial lipid occupying the area between densely packed protein units in acetylcholine receptor-rich membranes."}
{"id": "PMID:212746", "title": "Rat oocyte maturation in vitro: relief of cyclic AMP inhibition by gonadotropins.", "content": "The hormone-independent, spontaneous maturation that rat oocytes undergo in vitro can be inhibited by derivatives of cyclic AMP and inhibitors of cyclic nucleotide phosphodiesterase. In this study, we have shown that this inhibition of maturation can be partially relieved by preparations of ovine and rat luteinizing hormone or follicle-stimulating hormone. The ability of gonadotropins to foster the resumption of maturation in cultures of cyclic AMP-inhibited oocytes suggests that this system is suitable for studies of the hormonal control of oocyte development. The dose and time dependency of the response to gonadotropins has been examined in order to study the role of these hormones in oocyte maturation and to compare this effect to other known responses of the cumulus-oocyte complex. These studies show that highly purified preparations of rat gonadotropins are less effective inducers of maturation than the more commonly used, but considerably less purified, preparations of ovine gonadotropins. Almost complete relief of inhibition is observed, however, when the oocytes are exposed to a combination of rat luteinizing hormone and follicle-stimulating hormone. Oocyte maturation was not influenced by the sex steroids progesterone or 17beta-estradiol. Our results suggest that: (i) cyclic AMP is involved in the intrafollicular inhibition of oocyte maturation; (ii) both gonadotropins are required for maximal stimulation of the resumption of oocyte meiosis; and (iii) steroids are not involved in this response to gonadotropins.", "contents": "Rat oocyte maturation in vitro: relief of cyclic AMP inhibition by gonadotropins. The hormone-independent, spontaneous maturation that rat oocytes undergo in vitro can be inhibited by derivatives of cyclic AMP and inhibitors of cyclic nucleotide phosphodiesterase. In this study, we have shown that this inhibition of maturation can be partially relieved by preparations of ovine and rat luteinizing hormone or follicle-stimulating hormone. The ability of gonadotropins to foster the resumption of maturation in cultures of cyclic AMP-inhibited oocytes suggests that this system is suitable for studies of the hormonal control of oocyte development. The dose and time dependency of the response to gonadotropins has been examined in order to study the role of these hormones in oocyte maturation and to compare this effect to other known responses of the cumulus-oocyte complex. These studies show that highly purified preparations of rat gonadotropins are less effective inducers of maturation than the more commonly used, but considerably less purified, preparations of ovine gonadotropins. Almost complete relief of inhibition is observed, however, when the oocytes are exposed to a combination of rat luteinizing hormone and follicle-stimulating hormone. Oocyte maturation was not influenced by the sex steroids progesterone or 17beta-estradiol. Our results suggest that: (i) cyclic AMP is involved in the intrafollicular inhibition of oocyte maturation; (ii) both gonadotropins are required for maximal stimulation of the resumption of oocyte meiosis; and (iii) steroids are not involved in this response to gonadotropins."}
{"id": "PMID:212747", "title": "Simian virus 40 A gene function: DNA content analysis of Chinese hamster cells transformed by an early temperature-sensitive virus mutant.", "content": "Replication of two Chinese hamster embryo cell lines transformed by an early temperature-sensitive mutant of simian virus 40, tsA58, was examined by flow microfluorometry and autoradiography of [3H]thymidine-labeled cells in order to determine whether transformed cell DNA synthesis is initiated by the virus A gene. At the permissive temperature (37 degrees), cells transformed by the mutant were like the wild-type virus transformants in appearance, colony-forming ability, high saturation density, and rapid replication. At the nonpermissive temperature (40.5 degrees), the tsA58 transformed cells resembled normal embryo fibroblasts and seem to return to normal growth patterns. Although both mutant transformed cell lines at 40.5 degrees appeared to cease growth at low saturation density, the cells did not enter a resting state, but continued to replicate. The cultures were maintained at low densities by a balance among cell replication, cell death, and sloughing of dead cells into the supernatant. These results suggest that the simian virus 40 A gene function effected by the tsA58 mutation does not prevent Chinese hamster embryo transformed cells from entering a resting state, although the gene may control other phenotypic characteristics of transformation.", "contents": "Simian virus 40 A gene function: DNA content analysis of Chinese hamster cells transformed by an early temperature-sensitive virus mutant. Replication of two Chinese hamster embryo cell lines transformed by an early temperature-sensitive mutant of simian virus 40, tsA58, was examined by flow microfluorometry and autoradiography of [3H]thymidine-labeled cells in order to determine whether transformed cell DNA synthesis is initiated by the virus A gene. At the permissive temperature (37 degrees), cells transformed by the mutant were like the wild-type virus transformants in appearance, colony-forming ability, high saturation density, and rapid replication. At the nonpermissive temperature (40.5 degrees), the tsA58 transformed cells resembled normal embryo fibroblasts and seem to return to normal growth patterns. Although both mutant transformed cell lines at 40.5 degrees appeared to cease growth at low saturation density, the cells did not enter a resting state, but continued to replicate. The cultures were maintained at low densities by a balance among cell replication, cell death, and sloughing of dead cells into the supernatant. These results suggest that the simian virus 40 A gene function effected by the tsA58 mutation does not prevent Chinese hamster embryo transformed cells from entering a resting state, although the gene may control other phenotypic characteristics of transformation."}
{"id": "PMID:212748", "title": "Processing of 60,000-dalton sarc gene protein synthesized by cell-free translation.", "content": "In this report we show that antiserum prepared against the Mr60,000 transformation-specific antigen of Rous sarcoma virus immunoprecipitates both the Mr60,000 and Mr 25,000 transformation-specific proteins that are synthesized by cell-free translation of virion RNA; however, in the cell-free system the Mr 60,000 protein appears to be synthesized as a precursor that is approximately Mr 2000 larger than the [35S]-methionine-labeled protein immunoprecipitated from Rous sarcoma virus-infected cells. Peptide mapping of the cell-free translation product and of this cellular protein has confirmed that they are structurally related to one another. The addition of membrane vesicles to the reticulocyte lysate system during translation specifically cleaves a Mr 2000 segment from the Mr 60,000 protein so that it comigrates with the cellular species. Secretory proteins and probably at least some integral membrane proteins are synthesized with short hydrophobic signal sequences at their NH2 terminus. Two facts suggest that the segment lost from the Mr 60,000 transformation-specific protein is a signal sequence: (i) the membrane vesicles process the Mr 60,000 protein only during translation, and (ii) the processed protein is sequestered by the vesicles.", "contents": "Processing of 60,000-dalton sarc gene protein synthesized by cell-free translation. In this report we show that antiserum prepared against the Mr60,000 transformation-specific antigen of Rous sarcoma virus immunoprecipitates both the Mr60,000 and Mr 25,000 transformation-specific proteins that are synthesized by cell-free translation of virion RNA; however, in the cell-free system the Mr 60,000 protein appears to be synthesized as a precursor that is approximately Mr 2000 larger than the [35S]-methionine-labeled protein immunoprecipitated from Rous sarcoma virus-infected cells. Peptide mapping of the cell-free translation product and of this cellular protein has confirmed that they are structurally related to one another. The addition of membrane vesicles to the reticulocyte lysate system during translation specifically cleaves a Mr 2000 segment from the Mr 60,000 protein so that it comigrates with the cellular species. Secretory proteins and probably at least some integral membrane proteins are synthesized with short hydrophobic signal sequences at their NH2 terminus. Two facts suggest that the segment lost from the Mr 60,000 transformation-specific protein is a signal sequence: (i) the membrane vesicles process the Mr 60,000 protein only during translation, and (ii) the processed protein is sequestered by the vesicles."}
{"id": "PMID:212749", "title": "Regulation of corneal collagenase production: epithelial-stromal cell interactions.", "content": "Mixtures of epithelial and stromal cells isolated from normal adult rabbit cornea, when cocultured in the presence of cytochalasin B, produced latent collagenase, whereas neither cell type alone, nor the mixture in the absence of this agent, did so. The enzyme, a characteristic animal collagenase, required proteolytic activation. The relative concentrations of epithelial and stromal cells had a profound effect on on collagenase production, the enzyme activity bieng directly proportional to the number of stromal cells but inversely proportional to the number of epithelial cells. The amount of enzyme released into the medium was also directly proportional to cytochalasin B concentration. Media conditioned by cytochalasin B-treated epithelial or stromal cells did not stimulate collagenase secretion by the other cell type. The data suggest direct cell contact or close proximity as the mode of productive interaction and tentatively identify the stromal cell as the source of enzyme and the epithelial cell as a stimulator.", "contents": "Regulation of corneal collagenase production: epithelial-stromal cell interactions. Mixtures of epithelial and stromal cells isolated from normal adult rabbit cornea, when cocultured in the presence of cytochalasin B, produced latent collagenase, whereas neither cell type alone, nor the mixture in the absence of this agent, did so. The enzyme, a characteristic animal collagenase, required proteolytic activation. The relative concentrations of epithelial and stromal cells had a profound effect on on collagenase production, the enzyme activity bieng directly proportional to the number of stromal cells but inversely proportional to the number of epithelial cells. The amount of enzyme released into the medium was also directly proportional to cytochalasin B concentration. Media conditioned by cytochalasin B-treated epithelial or stromal cells did not stimulate collagenase secretion by the other cell type. The data suggest direct cell contact or close proximity as the mode of productive interaction and tentatively identify the stromal cell as the source of enzyme and the epithelial cell as a stimulator."}
{"id": "PMID:212750", "title": "Depression of cytidine 3':5'-cyclic monophosphate phosphodiesterase activity in developing tissues of guinea pigs.", "content": "Changes in levels of the newly discovered cytidine 3':5'-cyclic monophosphate (cyclic CMP) phosphodiesterase in some representative tissues (cerebral cortex, kidney, intestine, liver, heart, and lung) of guinea pigs from various developmental stages (fetus, neonate, pup, and adult) were studied and compared with those of cyclic AMP and cyclic GMP phosphodiesterases in the same tissues. It was observed that the tissue levels of cyclic CMP phosphodiesterase were invariably the lowest in every one of the fetal tissues examined, the highest in the corresponding tissues from the pups and adult, with intermediate levels seen in some neonatal tissues. The patterns of the ontogenetic changes in levels of cyclic AMP and cyclic GMP phosphodiesterase activities, however, were variable and tissue specific. These findings suggest that the depressed cyclic CMP phosphodiesterase activity (hence, the elevated cyclic CMP concentration) is perhaps a common factor in developing tissues undergoing rapid cell proliferation. The data also suggest that metabolism of cyclic CMP is perhaps more closely related to cell proliferation than the metabolism of cyclic AMP or cyclic GMP.", "contents": "Depression of cytidine 3':5'-cyclic monophosphate phosphodiesterase activity in developing tissues of guinea pigs. Changes in levels of the newly discovered cytidine 3':5'-cyclic monophosphate (cyclic CMP) phosphodiesterase in some representative tissues (cerebral cortex, kidney, intestine, liver, heart, and lung) of guinea pigs from various developmental stages (fetus, neonate, pup, and adult) were studied and compared with those of cyclic AMP and cyclic GMP phosphodiesterases in the same tissues. It was observed that the tissue levels of cyclic CMP phosphodiesterase were invariably the lowest in every one of the fetal tissues examined, the highest in the corresponding tissues from the pups and adult, with intermediate levels seen in some neonatal tissues. The patterns of the ontogenetic changes in levels of cyclic AMP and cyclic GMP phosphodiesterase activities, however, were variable and tissue specific. These findings suggest that the depressed cyclic CMP phosphodiesterase activity (hence, the elevated cyclic CMP concentration) is perhaps a common factor in developing tissues undergoing rapid cell proliferation. The data also suggest that metabolism of cyclic CMP is perhaps more closely related to cell proliferation than the metabolism of cyclic AMP or cyclic GMP."}
{"id": "PMID:212751", "title": "Age-dependent relaxation of gene repression: increase of endogenous murine leukemia virus-related and globin-related RNA in brain and liver of mice.", "content": "A progressive loss in the ability of cells to maintain their normal specialized states of differentiation could be the common denominator underlying much of the physiology and pathology associated with the mammalian aging process. We investigated this possibility by searching for an age-dependent derepression of endogenous genes in tissues in which they are not normally expected to be expressed. Complementary DNA (cDNA) probes to globin genes and to the murine leukemia type C RNA virus (MuLV) genome were used to detect the presence of RNA complementary to these genes in RNA extracted from brain and liver in young and old mice. Significant amounts of globin RNA were found in brain nuclei and cytoplasm. No age difference was found in the globin RNA sequences present, but the number of globin RNA molecules increased from about 15 in 6-month to 34 in 27-month-old animals for nuclei and 280 in 6-month to 500 in 27-month-old animals for cytoplasm. Similar results were found for liver. RNA complementary to the MuLV cDNA probe was also found but, in contrast to globin, the different RNA sequences increased in both brain and liver nuclei from about 45% of the MuLV genome in 6-month to 72% in 27-month-old animals. The number of MuLV-related RNA molecules remained constant at about 22 and 38 per nuclei for brain and liver, respectively. Derepression of genes of this magnitude could result in a time-dependent increase in virus-related diseases and a general deterioration of the organism.", "contents": "Age-dependent relaxation of gene repression: increase of endogenous murine leukemia virus-related and globin-related RNA in brain and liver of mice. A progressive loss in the ability of cells to maintain their normal specialized states of differentiation could be the common denominator underlying much of the physiology and pathology associated with the mammalian aging process. We investigated this possibility by searching for an age-dependent derepression of endogenous genes in tissues in which they are not normally expected to be expressed. Complementary DNA (cDNA) probes to globin genes and to the murine leukemia type C RNA virus (MuLV) genome were used to detect the presence of RNA complementary to these genes in RNA extracted from brain and liver in young and old mice. Significant amounts of globin RNA were found in brain nuclei and cytoplasm. No age difference was found in the globin RNA sequences present, but the number of globin RNA molecules increased from about 15 in 6-month to 34 in 27-month-old animals for nuclei and 280 in 6-month to 500 in 27-month-old animals for cytoplasm. Similar results were found for liver. RNA complementary to the MuLV cDNA probe was also found but, in contrast to globin, the different RNA sequences increased in both brain and liver nuclei from about 45% of the MuLV genome in 6-month to 72% in 27-month-old animals. The number of MuLV-related RNA molecules remained constant at about 22 and 38 per nuclei for brain and liver, respectively. Derepression of genes of this magnitude could result in a time-dependent increase in virus-related diseases and a general deterioration of the organism."}
{"id": "PMID:212752", "title": "Viable deletion mutants in the simian virus 40 early region.", "content": "For the purpose of isolating hr-t-like mutants of simian virus 40, we have constructed variants that have lost the unique site for the restriction enzyme Taq I at 0.565. Five mutants have been isolated and characterized by restriction enzyme analysis. All of them produce a normal size T antigen. Four produce a t antigen reduced in size as well as in amount; the fifth one does not seem to make any t antigen at all. The ability of these mutants to transform mouse cells in vitro, as tested by anchorage dependence, is clearly altered; however, the defect is only partial. In the same test, the mutants can complement a tsA mutant for transformation and therefore define a second complementation group in the simian virus 40 early region.", "contents": "Viable deletion mutants in the simian virus 40 early region. For the purpose of isolating hr-t-like mutants of simian virus 40, we have constructed variants that have lost the unique site for the restriction enzyme Taq I at 0.565. Five mutants have been isolated and characterized by restriction enzyme analysis. All of them produce a normal size T antigen. Four produce a t antigen reduced in size as well as in amount; the fifth one does not seem to make any t antigen at all. The ability of these mutants to transform mouse cells in vitro, as tested by anchorage dependence, is clearly altered; however, the defect is only partial. In the same test, the mutants can complement a tsA mutant for transformation and therefore define a second complementation group in the simian virus 40 early region."}
{"id": "PMID:212753", "title": "Another chromosomal assignment for a simian virus 40 integration site in human cells.", "content": "Somatic cell hybrids derived from fusion of GM637, a human cell line transformed by simian virus 40, and mouse B82 cells were examined for simian virus 40 T antigen, V antigen, and viral DNA. All hybrid cell lines that contained viral DNA were T-antigen positive. Cells that did not have viral DNA were T-antigen negative. We determined that there is a single viral insertion in these hybrid cells. Correlation of T-antigen expression and viral DNA with the partial complements of the human genome retained in the hybrids shwed that the inserted viral genome is in human chromosome 8. The integrated viral DNA is stable; free viral DNA found in GM637 does not insert at other potential sites in the human genome.", "contents": "Another chromosomal assignment for a simian virus 40 integration site in human cells. Somatic cell hybrids derived from fusion of GM637, a human cell line transformed by simian virus 40, and mouse B82 cells were examined for simian virus 40 T antigen, V antigen, and viral DNA. All hybrid cell lines that contained viral DNA were T-antigen positive. Cells that did not have viral DNA were T-antigen negative. We determined that there is a single viral insertion in these hybrid cells. Correlation of T-antigen expression and viral DNA with the partial complements of the human genome retained in the hybrids shwed that the inserted viral genome is in human chromosome 8. The integrated viral DNA is stable; free viral DNA found in GM637 does not insert at other potential sites in the human genome."}
{"id": "PMID:212754", "title": "Selective association of murine T lymphoblastoid cell surface alloantigens with Mycoplasma hyorhinis.", "content": "Mycoplasma hyorhinis, isolated by isopycnic centrifugation from supernatants of a persistently infected murine T lymphoblastoid cell line, demonstrated the presence of the Thy-1.1 differentiation alloantigen and H-2Kk histocompatibility antigens. The murine leukemia virus-related gp70 antigen also present on the surface of these lymphoblastoid cells was absent from mycoplasma preparations. Quantitative assessment of Thy-1.1 present in preparations of M. hyorhinis revealed a specific activity greater or equal to that of membrane preparations from lymphoblastoid cells, suggesting a marked accumulation of this T lymphoblastoid cells, suggesting a marked accumulation of this T lymphocyte antigen by membrane-associated mycoplasmas. The accumulation of the Thy-1.1 antigen in association with purified mycoplasmas was also demonstrated in lymphoblastoid cells experimentally infected with a defined culture of M. hyorhinis.", "contents": "Selective association of murine T lymphoblastoid cell surface alloantigens with Mycoplasma hyorhinis. Mycoplasma hyorhinis, isolated by isopycnic centrifugation from supernatants of a persistently infected murine T lymphoblastoid cell line, demonstrated the presence of the Thy-1.1 differentiation alloantigen and H-2Kk histocompatibility antigens. The murine leukemia virus-related gp70 antigen also present on the surface of these lymphoblastoid cells was absent from mycoplasma preparations. Quantitative assessment of Thy-1.1 present in preparations of M. hyorhinis revealed a specific activity greater or equal to that of membrane preparations from lymphoblastoid cells, suggesting a marked accumulation of this T lymphoblastoid cells, suggesting a marked accumulation of this T lymphocyte antigen by membrane-associated mycoplasmas. The accumulation of the Thy-1.1 antigen in association with purified mycoplasmas was also demonstrated in lymphoblastoid cells experimentally infected with a defined culture of M. hyorhinis."}
{"id": "PMID:212755", "title": "Characterization of a feline sarcoma virus-coded antigen (FOCMA-S) by radioimmunoassay.", "content": "A radioimmunoassay has been developed that detects a unique antigen encoded by the genome of the feline sarcoma virus (FeSV). Pseudotype viral particles containing an FeSV-specific polyprotein (p85) were used both as a source of antigen and to prepare specific antisera in rabbits. Because p85 contains antigens related to two structural proteins (p15 and p12) of feline leukemia virus (FeLV), antibodies directed to these were adsorbed with purified FeLV proteins. The adsorbed rabbit antiserum bound to antigenic determinants (designated FOCMA-S) which are also present in p85 and reacted specifically in immunofluorescence tests with rat cells transformed by FeSV and with FOCMA-positive cat lymphoid tumor cells. Competition assays detect FOCMA-S in pseudotype type C viruses rescued from FeSV-transformed mink and rat cells but not in heterologous type C helper viruses or in FeLV. A crossreactive antigen was also detected in pseudotypes of Kirsten sarcoma virus. The assay permits the quantitative measurement of an FeSV-coded protein whose expression is associated with viral transformation.", "contents": "Characterization of a feline sarcoma virus-coded antigen (FOCMA-S) by radioimmunoassay. A radioimmunoassay has been developed that detects a unique antigen encoded by the genome of the feline sarcoma virus (FeSV). Pseudotype viral particles containing an FeSV-specific polyprotein (p85) were used both as a source of antigen and to prepare specific antisera in rabbits. Because p85 contains antigens related to two structural proteins (p15 and p12) of feline leukemia virus (FeLV), antibodies directed to these were adsorbed with purified FeLV proteins. The adsorbed rabbit antiserum bound to antigenic determinants (designated FOCMA-S) which are also present in p85 and reacted specifically in immunofluorescence tests with rat cells transformed by FeSV and with FOCMA-positive cat lymphoid tumor cells. Competition assays detect FOCMA-S in pseudotype type C viruses rescued from FeSV-transformed mink and rat cells but not in heterologous type C helper viruses or in FeLV. A crossreactive antigen was also detected in pseudotypes of Kirsten sarcoma virus. The assay permits the quantitative measurement of an FeSV-coded protein whose expression is associated with viral transformation."}
{"id": "PMID:212756", "title": "Isolation of a herpesvirus-specific DNA polymerase from tissues of an American patient with Burkitt lymphoma.", "content": "A DNA polymerase (DNA nucleotidyltransferase) has been partially purified from a neck mass of an American patient with Burkitt lymphoma and separated from the cellular DNA polymerases. The molecular weight of the enzyme was approximately 90,000. The enzyme differs from the cellular DNA polymerases, but resembles herpes-virus-induced DNA polymerase in its primer template preference, high monovalent cation requirement for activity, and sensitivity to phosphonoacetate. Enzyme activity was inhibited specifically by an antibody directed against herpes-simplex-virus-induced DNA polymerase but not by antibodies directed against DNA polymerase alpha of HeLa cells and DNA polymerase gamma of a normal human lymphoblast cell line, NC37. Although serum of the patient with Burkitt lymphoma contained high Epstein-Barr virus titer, addition of the serum to the assay mixture did not have any effect on the activity of Burkitt lymphoma DNA polymerase. Tissues from spleen and liver of the patient with Burkitt lymphoma did not contain the herpes-virus-induced DNA polymerase. Detection of the herpes virus polymerase in the Burkitt lymphoma tissue provides additional evidence for the association of Epstein-Barr virus with this malignancy.", "contents": "Isolation of a herpesvirus-specific DNA polymerase from tissues of an American patient with Burkitt lymphoma. A DNA polymerase (DNA nucleotidyltransferase) has been partially purified from a neck mass of an American patient with Burkitt lymphoma and separated from the cellular DNA polymerases. The molecular weight of the enzyme was approximately 90,000. The enzyme differs from the cellular DNA polymerases, but resembles herpes-virus-induced DNA polymerase in its primer template preference, high monovalent cation requirement for activity, and sensitivity to phosphonoacetate. Enzyme activity was inhibited specifically by an antibody directed against herpes-simplex-virus-induced DNA polymerase but not by antibodies directed against DNA polymerase alpha of HeLa cells and DNA polymerase gamma of a normal human lymphoblast cell line, NC37. Although serum of the patient with Burkitt lymphoma contained high Epstein-Barr virus titer, addition of the serum to the assay mixture did not have any effect on the activity of Burkitt lymphoma DNA polymerase. Tissues from spleen and liver of the patient with Burkitt lymphoma did not contain the herpes-virus-induced DNA polymerase. Detection of the herpes virus polymerase in the Burkitt lymphoma tissue provides additional evidence for the association of Epstein-Barr virus with this malignancy."}
{"id": "PMID:212757", "title": "Formation of high density lipoprotein2-like particles during lipolysis of very low density lipoproteins in vitro.", "content": "The effects of lipolysis of human plasma very low density lipoprotein (VLDL) on the structure and composition of high density lipoproteins (HDL) have been investigated. Lipolysis was performed in a controlled system in vitro containing VLDL (d less than 1.006 g/ml) and HDL3 (d = 1.125-1.210 g/ml) from human plasma and lipoprotein lipase (EC 3.1.1.34) purified from bovine milk. Lipolysis of VLDL caused profound changes in HDL3. Protein, phospholipid, and cholesterol liberated from VLDL during its lipolysis were transferred to the HDL3 particles. As a consequence of this in vitro transfer, the chemical composition and biophysical properties of HDL3 were substantially altered. The newly formed particles exhibited a flotation rate (F01.20) of 6.7 and a hydrated density of 1.110 g/ml. The chemical composition closely resembled that of native HDL2, and their size was slightly larger than that of the precursor HDL3. When HDL3 and postlipolysis HDL2 were subjected to ultracentrifugation under flotation velocity and equilibrium conditions, both proved to be stable particles. These results, when extrapolated to in vivo conditions, suggest an important metabolic relationship between the levels of circulating VLDL and HDL2 in plasma. This relationship now permits a reasonable explanation for numerous in vivo observations in which the levels of VLDL and HDL2 change reciprocally.", "contents": "Formation of high density lipoprotein2-like particles during lipolysis of very low density lipoproteins in vitro. The effects of lipolysis of human plasma very low density lipoprotein (VLDL) on the structure and composition of high density lipoproteins (HDL) have been investigated. Lipolysis was performed in a controlled system in vitro containing VLDL (d less than 1.006 g/ml) and HDL3 (d = 1.125-1.210 g/ml) from human plasma and lipoprotein lipase (EC 3.1.1.34) purified from bovine milk. Lipolysis of VLDL caused profound changes in HDL3. Protein, phospholipid, and cholesterol liberated from VLDL during its lipolysis were transferred to the HDL3 particles. As a consequence of this in vitro transfer, the chemical composition and biophysical properties of HDL3 were substantially altered. The newly formed particles exhibited a flotation rate (F01.20) of 6.7 and a hydrated density of 1.110 g/ml. The chemical composition closely resembled that of native HDL2, and their size was slightly larger than that of the precursor HDL3. When HDL3 and postlipolysis HDL2 were subjected to ultracentrifugation under flotation velocity and equilibrium conditions, both proved to be stable particles. These results, when extrapolated to in vivo conditions, suggest an important metabolic relationship between the levels of circulating VLDL and HDL2 in plasma. This relationship now permits a reasonable explanation for numerous in vivo observations in which the levels of VLDL and HDL2 change reciprocally."}
{"id": "PMID:212758", "title": "A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks.", "content": "Particles with properties similar to those associated with human hepatitis B were found in serum from woodchucks with chronic hepatitis and hepatocellular carcinoma. It is suggested that woodchuck hepatitis virus is a second member of a novel class of viruses represented by the human hepatitis B virus.", "contents": "A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Particles with properties similar to those associated with human hepatitis B were found in serum from woodchucks with chronic hepatitis and hepatocellular carcinoma. It is suggested that woodchuck hepatitis virus is a second member of a novel class of viruses represented by the human hepatitis B virus."}
{"id": "PMID:212759", "title": "Endogenous RNA tumor viruses are activated during chemical induction of murine plasmacytomas.", "content": "Plasmacytomas are induced in BALB/c mice by the intraperitoneal injection of pristane (2,6,10,14-tetra-methylpentadecane) after a latent period of six months and more [Anderson, P. N. & Potter, M. (1969) Nature 222, 994-995]. Spleen cells mesenteric lymph node cells, thoracic lymph node cells, and peritoneal exudate cells were prepared from pristane-treated and control uninjected BALB/c mice during the course of a 10-month period, and these cell suspensions were tested for the release of infectious murine leukemia viruses. Endogenous ecotropic and xenotropic murine leukemia viruses were expressed in pristane-treated mice during the latter part of the tumor induction period, in those cell populations in which transformed plasma cells appear, namely, peritoneal exudate cells and thoracic lymph node cells. The significance of preferential expression of both ecotropic and xenotropic murine leukemia virus in target cell populations following the administration of a carcinogen is discussed in terms of the possible formation of an oncogenic variant virus.", "contents": "Endogenous RNA tumor viruses are activated during chemical induction of murine plasmacytomas. Plasmacytomas are induced in BALB/c mice by the intraperitoneal injection of pristane (2,6,10,14-tetra-methylpentadecane) after a latent period of six months and more [Anderson, P. N. & Potter, M. (1969) Nature 222, 994-995]. Spleen cells mesenteric lymph node cells, thoracic lymph node cells, and peritoneal exudate cells were prepared from pristane-treated and control uninjected BALB/c mice during the course of a 10-month period, and these cell suspensions were tested for the release of infectious murine leukemia viruses. Endogenous ecotropic and xenotropic murine leukemia viruses were expressed in pristane-treated mice during the latter part of the tumor induction period, in those cell populations in which transformed plasma cells appear, namely, peritoneal exudate cells and thoracic lymph node cells. The significance of preferential expression of both ecotropic and xenotropic murine leukemia virus in target cell populations following the administration of a carcinogen is discussed in terms of the possible formation of an oncogenic variant virus."}
{"id": "PMID:212760", "title": "Serological characterization of B-tropic viruses of C57BL mice: possible origin by recombination of endogenous N-tropic and xenotropic viruses.", "content": "The serological properties of the gag gene products p15 and p12 of N- and B-tropic viruses of C57BL mice have been examined. Although these viruses were serologically identical by competition assays for proteins gp71 and p30, they were readily distinguishable in competition assays for proteins p15 and p12. Two isolates of N-tropic viruses had p12s serologically indistinguishable from AKR murine leukemia virus p12, while two B-tropic isolates had distinctly different p12s. The latter p12s were serologically indistinguishable from the p12 purified from the B-tropic radiation leukemia virus (RadLV)/VL-3. Moreover, this p12 was indistinguishable from the p12 of the endogenous C57BL/Ka xenotropic virus. Similarly, the p15s of the B-tropic viruses were serologically distinct from the AKR murine leukemia virus type of p15, as was the p15 of one C57BL N-tropic virus, whilc another N-tropic isolate had a p15 identical to the AKR murine leukemia virus p15. These results are interprered to suggest that the endogenous N-tropic virus of C57BL mice undergoes recombination with the endogenous, xenotropic virus and that this mechanism is involved in the generation of B-tropic viruses in C57BL mice.", "contents": "Serological characterization of B-tropic viruses of C57BL mice: possible origin by recombination of endogenous N-tropic and xenotropic viruses. The serological properties of the gag gene products p15 and p12 of N- and B-tropic viruses of C57BL mice have been examined. Although these viruses were serologically identical by competition assays for proteins gp71 and p30, they were readily distinguishable in competition assays for proteins p15 and p12. Two isolates of N-tropic viruses had p12s serologically indistinguishable from AKR murine leukemia virus p12, while two B-tropic isolates had distinctly different p12s. The latter p12s were serologically indistinguishable from the p12 purified from the B-tropic radiation leukemia virus (RadLV)/VL-3. Moreover, this p12 was indistinguishable from the p12 of the endogenous C57BL/Ka xenotropic virus. Similarly, the p15s of the B-tropic viruses were serologically distinct from the AKR murine leukemia virus type of p15, as was the p15 of one C57BL N-tropic virus, whilc another N-tropic isolate had a p15 identical to the AKR murine leukemia virus p15. These results are interprered to suggest that the endogenous N-tropic virus of C57BL mice undergoes recombination with the endogenous, xenotropic virus and that this mechanism is involved in the generation of B-tropic viruses in C57BL mice."}
{"id": "PMID:212761", "title": "Activation of endogenous type C virus in BALB/c mouse cells by herpesvirus DNA.", "content": "Several virion and nonvirion DNAs were tested for the ability to activate endogenous type C virus in BALB/c-derived mouse cells using the calcium precipitation technique. The DNAs from all herpesviruses tested activated xenotropic type C virus synthesis. These included DNAs from herpes simplex virus types 1 and 2, Epstein-Barr virus, human cytomegalovirus, SA8 virus, infectious bovine rhinotracheitis virus, pseudorabies virus, and herpes saimiri virus (M-DNA). In contrast, DNAs from vaccinia virus, simian virus 40, primate cells, bacteria, mycoplasma, and salmon sperm showed no ability to activate type C virus when tested under the same conditions. Several herpesviruses and vaccinia virus, which were highly infectious for the BALB/c cells used, were tested for their ability to activate type C virus after UV irradiation. All herpesviruses tested were positive, while vaccinia virus was negative. Unirradiated simian virus 40 also showed no ability to activate type C virus. Activation of type C virus by DNA from herpes simplex virus was observed after shearing or sonication of the DNA to an average size of 3 x 10(6) daltons, but was not observed with DNA sonicated to an average size of 1 x 10(6) daltons. Alkali denaturation of DNA from herpes simplex virus or treatment with DNase, but not RNase, destroyed its ability to activate type C virus, as did crosslinking of the DNA with 4,5',8-trimethylpsoralen (psoralen) and light.", "contents": "Activation of endogenous type C virus in BALB/c mouse cells by herpesvirus DNA. Several virion and nonvirion DNAs were tested for the ability to activate endogenous type C virus in BALB/c-derived mouse cells using the calcium precipitation technique. The DNAs from all herpesviruses tested activated xenotropic type C virus synthesis. These included DNAs from herpes simplex virus types 1 and 2, Epstein-Barr virus, human cytomegalovirus, SA8 virus, infectious bovine rhinotracheitis virus, pseudorabies virus, and herpes saimiri virus (M-DNA). In contrast, DNAs from vaccinia virus, simian virus 40, primate cells, bacteria, mycoplasma, and salmon sperm showed no ability to activate type C virus when tested under the same conditions. Several herpesviruses and vaccinia virus, which were highly infectious for the BALB/c cells used, were tested for their ability to activate type C virus after UV irradiation. All herpesviruses tested were positive, while vaccinia virus was negative. Unirradiated simian virus 40 also showed no ability to activate type C virus. Activation of type C virus by DNA from herpes simplex virus was observed after shearing or sonication of the DNA to an average size of 3 x 10(6) daltons, but was not observed with DNA sonicated to an average size of 1 x 10(6) daltons. Alkali denaturation of DNA from herpes simplex virus or treatment with DNase, but not RNase, destroyed its ability to activate type C virus, as did crosslinking of the DNA with 4,5',8-trimethylpsoralen (psoralen) and light."}
{"id": "PMID:212766", "title": "Mouse brain deoxyglucose uptake after footshock, ACTH analogs, alpha-MSH, corticosterone or lysine vasopressin.", "content": "The cerebral uptake of subcutaneously injected [3H]2-deoxy-D-glucose (2DG) in 16 brain regions was examined following 30 noncontingent random footshocks or the acute injection of saline, ACTH1-24 (0.5 microgram/g), ACTH/MSH4-10 (0.25 microgram/g), [D-Phe7]ACTH4-10 (0.25 microgram/g), [Met4SO2,D-Lys8,Phe9]ACTH4-9 (0.01 microgram/g), ALPHA-MSH (0.5 microgram/g), corticosterone (2.5 microgram/g) or lysine vasopressin (0.05 microgram/g). Footshock selectively decreased 2DG uptake in parietal cortex and brain stem, and increased that in the hypothalamus. Whole brain 2DG uptake was decreased by injection of saline or most of the hormones relative to uninjected animals, but this effect was probably peripheral since plasma glucose content was increased by the injections. The only regionally specific effect of the hormones was an increased 2DG uptake in olfactory bulb by saline, ACTH/MSH4-10 And corticosterone relative to uninjected animals. Since alpha-MSH had been reported previously to decrease blood flow (measured by antipyrene uptake) in all brain regions except occipital cortex [5,6], we directly compared antipyrene uptake with 2DG uptake in the same animals using a double-isotope procedure. The results revealed an increase in 2DG uptake relative to antipyrene in cortical regions relative to subcortical regions, contradicting earlier assumptions [19].", "contents": "Mouse brain deoxyglucose uptake after footshock, ACTH analogs, alpha-MSH, corticosterone or lysine vasopressin. The cerebral uptake of subcutaneously injected [3H]2-deoxy-D-glucose (2DG) in 16 brain regions was examined following 30 noncontingent random footshocks or the acute injection of saline, ACTH1-24 (0.5 microgram/g), ACTH/MSH4-10 (0.25 microgram/g), [D-Phe7]ACTH4-10 (0.25 microgram/g), [Met4SO2,D-Lys8,Phe9]ACTH4-9 (0.01 microgram/g), ALPHA-MSH (0.5 microgram/g), corticosterone (2.5 microgram/g) or lysine vasopressin (0.05 microgram/g). Footshock selectively decreased 2DG uptake in parietal cortex and brain stem, and increased that in the hypothalamus. Whole brain 2DG uptake was decreased by injection of saline or most of the hormones relative to uninjected animals, but this effect was probably peripheral since plasma glucose content was increased by the injections. The only regionally specific effect of the hormones was an increased 2DG uptake in olfactory bulb by saline, ACTH/MSH4-10 And corticosterone relative to uninjected animals. Since alpha-MSH had been reported previously to decrease blood flow (measured by antipyrene uptake) in all brain regions except occipital cortex [5,6], we directly compared antipyrene uptake with 2DG uptake in the same animals using a double-isotope procedure. The results revealed an increase in 2DG uptake relative to antipyrene in cortical regions relative to subcortical regions, contradicting earlier assumptions [19]."}
{"id": "PMID:212767", "title": "Involvement of brain cyclic AMP in the acute and chronic effects of morphine in the rat.", "content": "Incubation of cerebral cortical slices of rat brain with 3H-adenosine in the presence of varying concentrations of morphine in vitro resulted in a dose-related increase in 3H-cAMP formation. In in vivo experiments, the rate of 3H-cAMP formation in cortical slices both 45 min and 4 h after the acute s.c. administration of a 10 mg/kg dose of morphine was significantly greater than that for saline-treated controls. A significant enhancement of cortical 3H-cAMP formation likewise became apparent 72 hr after s.c. implantation of two morphine pellets. This was not evident after only 24 h. In similar experiments undertaken with hypothalamic tissue, however, the rate of conversion of 3H-adenosine to 3H-cAMP remained similar to that of the controls. Administration of exogenous cAMP antagonized the analgesic response to morphine in both nontolerant and tolerant rats and accelerated the development of tolerance to morphine. These results may provide further evidence for a role of cAMP in the mediation of the central actions of morphine.", "contents": "Involvement of brain cyclic AMP in the acute and chronic effects of morphine in the rat. Incubation of cerebral cortical slices of rat brain with 3H-adenosine in the presence of varying concentrations of morphine in vitro resulted in a dose-related increase in 3H-cAMP formation. In in vivo experiments, the rate of 3H-cAMP formation in cortical slices both 45 min and 4 h after the acute s.c. administration of a 10 mg/kg dose of morphine was significantly greater than that for saline-treated controls. A significant enhancement of cortical 3H-cAMP formation likewise became apparent 72 hr after s.c. implantation of two morphine pellets. This was not evident after only 24 h. In similar experiments undertaken with hypothalamic tissue, however, the rate of conversion of 3H-adenosine to 3H-cAMP remained similar to that of the controls. Administration of exogenous cAMP antagonized the analgesic response to morphine in both nontolerant and tolerant rats and accelerated the development of tolerance to morphine. These results may provide further evidence for a role of cAMP in the mediation of the central actions of morphine."}
{"id": "PMID:212768", "title": "Levodopa-mediated alteration in the activity of pyridoxal kinase in rat basal ganglia.", "content": "The acute intraperitoneal administration of 400 mg/kg of levodopa reduced the concentration of pyridoxal phosphate and increased the activity of pyridoxal kinase. The chronic oral administration of 100 mg/kg/day of levodopa did not alter the concentration of pyridoxal phosphate, but increased the activity of pyridoxal kinase in 7 days. This initial elevation in kinase activity returned to normal levels in 2 weeks, became reduced in 3 weeks and then fluctuated back to normal levels in 4 weeks. These results are interpreted to indicate that chronic intake of levodopa results in adaptive alteration in the activity of pyridoxal kinase. This maintains the steady-state concentration of pyridoxal phosphate in order to meet the levodopa-induced enhancement in decarboxylation reaction.", "contents": "Levodopa-mediated alteration in the activity of pyridoxal kinase in rat basal ganglia. The acute intraperitoneal administration of 400 mg/kg of levodopa reduced the concentration of pyridoxal phosphate and increased the activity of pyridoxal kinase. The chronic oral administration of 100 mg/kg/day of levodopa did not alter the concentration of pyridoxal phosphate, but increased the activity of pyridoxal kinase in 7 days. This initial elevation in kinase activity returned to normal levels in 2 weeks, became reduced in 3 weeks and then fluctuated back to normal levels in 4 weeks. These results are interpreted to indicate that chronic intake of levodopa results in adaptive alteration in the activity of pyridoxal kinase. This maintains the steady-state concentration of pyridoxal phosphate in order to meet the levodopa-induced enhancement in decarboxylation reaction."}
{"id": "PMID:212776", "title": "Tubular carcinoma of the breast. Mammographic appearance and pathological correlation.", "content": "Xeromammographic and pathological findings in 17 cases of tubular carcinoma of the breast are presented. No patients had axillary lymph node involvement. The mean lesion size was 0.95 cm. Thirteen lesions (76%) were clinically occult. Because of the characteristic histological pattern of infiltrative growth and marked desmoplasia, 81% (13/16) were seen on xeromammography as scirrhous masses, 19% (3/16) only as microcalcifications. None appeared as a well-circumscribed mass or poorly defined density.", "contents": "Tubular carcinoma of the breast. Mammographic appearance and pathological correlation. Xeromammographic and pathological findings in 17 cases of tubular carcinoma of the breast are presented. No patients had axillary lymph node involvement. The mean lesion size was 0.95 cm. Thirteen lesions (76%) were clinically occult. Because of the characteristic histological pattern of infiltrative growth and marked desmoplasia, 81% (13/16) were seen on xeromammography as scirrhous masses, 19% (3/16) only as microcalcifications. None appeared as a well-circumscribed mass or poorly defined density."}
{"id": "PMID:212777", "title": "The grain in the stone: a computer search for hidden CT patterns.", "content": "Relatively simple but time-consuming computer manipulations of basic CT images have been carried out. We have been unsuccessful in finding significant information when the skewness or kurtosis of the CT image is computed and displayed, but have found recognizable and useful new gray scale images upon reconstruction of sigma mode textures.", "contents": "The grain in the stone: a computer search for hidden CT patterns. Relatively simple but time-consuming computer manipulations of basic CT images have been carried out. We have been unsuccessful in finding significant information when the skewness or kurtosis of the CT image is computed and displayed, but have found recognizable and useful new gray scale images upon reconstruction of sigma mode textures."}
{"id": "PMID:212774", "title": "Effectiveness of a specially trained pharmacist in a rural community mental health center.", "content": "Pharmacists having training in psychopharmacology and psychiatry are being specially trained to function in community mental health centers as a resource in psychopharmacology and to provide direct care to patients. Management information data over a 3-year period from eight rural mental health clinics indicate that these pharmacists can successfully maintain large numbers of stabilized psychiatric patients within their communities. The cost of a pharmacist's services is, conservatively, one-half that of a psychiatrist's services. A followup study of the stabilized and active aftercare outpatients in the 10-county rural area in which the 8 clinics are located revealed that those patients who received all their direct care from the pharmacist were functioning at a slightly healthier level than the other aftercare patients. The pharmacist's patients indicated that they were at least as satisfied with their care as were the aftercare patients who received care from other mental health professionals. If the results of this study can be generalized to other community mental health centers in rural areas, a pharmacist can provide services effectively when psychiatrists are inaccessible or unavailable or when funds for mental health professionals are limited.", "contents": "Effectiveness of a specially trained pharmacist in a rural community mental health center. Pharmacists having training in psychopharmacology and psychiatry are being specially trained to function in community mental health centers as a resource in psychopharmacology and to provide direct care to patients. Management information data over a 3-year period from eight rural mental health clinics indicate that these pharmacists can successfully maintain large numbers of stabilized psychiatric patients within their communities. The cost of a pharmacist's services is, conservatively, one-half that of a psychiatrist's services. A followup study of the stabilized and active aftercare outpatients in the 10-county rural area in which the 8 clinics are located revealed that those patients who received all their direct care from the pharmacist were functioning at a slightly healthier level than the other aftercare patients. The pharmacist's patients indicated that they were at least as satisfied with their care as were the aftercare patients who received care from other mental health professionals. If the results of this study can be generalized to other community mental health centers in rural areas, a pharmacist can provide services effectively when psychiatrists are inaccessible or unavailable or when funds for mental health professionals are limited."}
{"id": "PMID:212778", "title": "Computed tomography in astrocytomas. A statistical analysis of the parameters of malignancy and the positive contrast-enhanced CT scan.", "content": "Four histopathological indices of malignancy--cellularity, pleomorphism, vascularity, and necrosis--were correlated with the positive-contrast CT scan in 84 patients with pathologically proved astrocytoma. Vascularity and necrosis correlated best with the scan in supratentorial tumors, while vascularity and cellularity correlated significantly with the scan in cerebellar astrocytomas. These findings indicate that the degree of malignancy of a supratentorial astrocytoma can be inferred from the contrast-enhanced scan, but that this is not generally possible with posterior fossa tumors.", "contents": "Computed tomography in astrocytomas. A statistical analysis of the parameters of malignancy and the positive contrast-enhanced CT scan. Four histopathological indices of malignancy--cellularity, pleomorphism, vascularity, and necrosis--were correlated with the positive-contrast CT scan in 84 patients with pathologically proved astrocytoma. Vascularity and necrosis correlated best with the scan in supratentorial tumors, while vascularity and cellularity correlated significantly with the scan in cerebellar astrocytomas. These findings indicate that the degree of malignancy of a supratentorial astrocytoma can be inferred from the contrast-enhanced scan, but that this is not generally possible with posterior fossa tumors."}
{"id": "PMID:212779", "title": "99mTc-pyrophosphate imaging in experimental mesenteric infarction: relationship of tracer uptake to the degree of ischemic injury.", "content": "Four-hour balloon occlusion of the cranial mesenteric artery in 13 dogs produced a spectrum of widespread ischemic injury to the small bowel ranging from superficial mucosal infarction to transmural infarction. Twenty-four hours after the beginning of balloon occlusion, 15 mCl of 99mTc-pyrophosphate was injected into the cranial mesenteric artery in 8 dogs and into a peripheral vein in 5. Gamma camera imaging of the abdomen followed three hours later. Four of 8 dogs injected intra-arterially showed positive images with full-thickness mucosal or transmural infarction. The 4 intravenously injected dogs with positive images had transmural infarction. Only minimal ischemic injury with superficial mucosal infarction was found in the 5 dogs with negative images. Tracer uptake per gram infarcted tissue was highest after intra-arterial injection. It was concluded that 99mTc-pyrophosphate allows external imaging of extensive intestinal infarctions after both intra-arterial and intravenous injection.", "contents": "99mTc-pyrophosphate imaging in experimental mesenteric infarction: relationship of tracer uptake to the degree of ischemic injury. Four-hour balloon occlusion of the cranial mesenteric artery in 13 dogs produced a spectrum of widespread ischemic injury to the small bowel ranging from superficial mucosal infarction to transmural infarction. Twenty-four hours after the beginning of balloon occlusion, 15 mCl of 99mTc-pyrophosphate was injected into the cranial mesenteric artery in 8 dogs and into a peripheral vein in 5. Gamma camera imaging of the abdomen followed three hours later. Four of 8 dogs injected intra-arterially showed positive images with full-thickness mucosal or transmural infarction. The 4 intravenously injected dogs with positive images had transmural infarction. Only minimal ischemic injury with superficial mucosal infarction was found in the 5 dogs with negative images. Tracer uptake per gram infarcted tissue was highest after intra-arterial injection. It was concluded that 99mTc-pyrophosphate allows external imaging of extensive intestinal infarctions after both intra-arterial and intravenous injection."}
{"id": "PMID:212786", "title": "Abnormalities resulting from intra-adnexal injection of glucose in the rabbit embryo--an experimental model of \"amniotic disease\".", "content": "Intra-adnexal injections of glucose into the rabbit embryo have induced amputations of digits or segments of limbs, congenital grooves, amniotic bands, club feet, syndactyly, hare lip, anencephaly, and ulcerations of the scalp. We have thus reproduced all the anomalies which are encountered in the clinical syndrome of \"amniotic disease.\" These anomalies result from destruction of the cutaneous epithelium and the subjacent mesenchymatous cells, and extravasation of blood with hematoma formation around the superficial vessels. This general mechanism explains most of these anomalies. Intra-adnexal injections of glucose thus constitute an external trauma for the embryo and is good experimental model of amniotic disease.", "contents": "Abnormalities resulting from intra-adnexal injection of glucose in the rabbit embryo--an experimental model of \"amniotic disease\". Intra-adnexal injections of glucose into the rabbit embryo have induced amputations of digits or segments of limbs, congenital grooves, amniotic bands, club feet, syndactyly, hare lip, anencephaly, and ulcerations of the scalp. We have thus reproduced all the anomalies which are encountered in the clinical syndrome of \"amniotic disease.\" These anomalies result from destruction of the cutaneous epithelium and the subjacent mesenchymatous cells, and extravasation of blood with hematoma formation around the superficial vessels. This general mechanism explains most of these anomalies. Intra-adnexal injections of glucose thus constitute an external trauma for the embryo and is good experimental model of amniotic disease."}
{"id": "PMID:212787", "title": "Prostaglandin I2 stimulation of granulosa cell cyclic AMP production.", "content": "The ability of prostaglandin I2 (PGI2) to stimulate cyclic AMP production by granulosa cells, isolated from intact immature rats, has been demonstrated in vitro. The minimal effective dose was 15 ng/ml, which was comparable to the minimal effective dose for PGE2. However, a concentration of 15 microgram/ml PGI2 was required to stimulate cyclic AMP production maximally, compared to a concentration of 1 microgram/ml PGE2, which produced the maximum response. It therefore appears that PGI2 is not more effective than PGE2 in stimulating cyclic AMP production in granulosa cells, and is possibly less effective. Submaximal concentrations of PGI2 appeared to be able to modify the stimulation of cyclic AMP production by follicle-stimulating hormone (FSH), but whether or not PGI2 plays any role in follicular function remains to be established.", "contents": "Prostaglandin I2 stimulation of granulosa cell cyclic AMP production. The ability of prostaglandin I2 (PGI2) to stimulate cyclic AMP production by granulosa cells, isolated from intact immature rats, has been demonstrated in vitro. The minimal effective dose was 15 ng/ml, which was comparable to the minimal effective dose for PGE2. However, a concentration of 15 microgram/ml PGI2 was required to stimulate cyclic AMP production maximally, compared to a concentration of 1 microgram/ml PGE2, which produced the maximum response. It therefore appears that PGI2 is not more effective than PGE2 in stimulating cyclic AMP production in granulosa cells, and is possibly less effective. Submaximal concentrations of PGI2 appeared to be able to modify the stimulation of cyclic AMP production by follicle-stimulating hormone (FSH), but whether or not PGI2 plays any role in follicular function remains to be established."}
{"id": "PMID:212788", "title": "Cholesterol arachidonate as a prostaglandin precursor in adrenocortical cells.", "content": "Rat adrenocortical cells were incubated with labeled arachidonate, and the radioactivity in unesterified fatty acids was reduced by washing with 2% albumin solutions. These cells were then incubated for two hours in the absence and presence of 7.1 x 10(-10)M ACTH. During subsequent incubation of prelabeled cells with ACTH, both the mass and radioactivity of arachidonate in adrenocortical cholesteryl esters was depleted to the same extent (30--32%). The released arachidonate was in part incorporated into phospholipids, and there was also a significant increase in unesterified arachidonic acid. During this period, there was also increased incorporation of arachidonate into labeled prostaglandins. Of this increase, 92% by isotope analysis, and 88% by radioimmunoassay techniques was attributable to prostaglandins of the E pathway. These data demonstrate that prostaglandin E synthesis is specifically increased during ACTH stimulation of rat adrenocortical cells and suggest that a major source of the arachidonate substrate for this synthesis is derived from hormone-dependent hydrolysis of cortical cholesteryl esters.", "contents": "Cholesterol arachidonate as a prostaglandin precursor in adrenocortical cells. Rat adrenocortical cells were incubated with labeled arachidonate, and the radioactivity in unesterified fatty acids was reduced by washing with 2% albumin solutions. These cells were then incubated for two hours in the absence and presence of 7.1 x 10(-10)M ACTH. During subsequent incubation of prelabeled cells with ACTH, both the mass and radioactivity of arachidonate in adrenocortical cholesteryl esters was depleted to the same extent (30--32%). The released arachidonate was in part incorporated into phospholipids, and there was also a significant increase in unesterified arachidonic acid. During this period, there was also increased incorporation of arachidonate into labeled prostaglandins. Of this increase, 92% by isotope analysis, and 88% by radioimmunoassay techniques was attributable to prostaglandins of the E pathway. These data demonstrate that prostaglandin E synthesis is specifically increased during ACTH stimulation of rat adrenocortical cells and suggest that a major source of the arachidonate substrate for this synthesis is derived from hormone-dependent hydrolysis of cortical cholesteryl esters."}
{"id": "PMID:212789", "title": "Interaction of prostaglandins and adenosine 5'-triphosphate in the noncholinergic neurotransmission in rabbit detrusor.", "content": "Part of the excitatory transmission in rabbit detrusor is noncholinergic and nonadrenergic, and prostaglandins (PGs) and adenosine 5'-triphosphate (ATP) have been implicated in this transmission. The present experiments investigate the possibility of an interaction between PGs and ATP in rabbit detrusor. Indomethacin (2.8 muM) depressed the contraction produced by ATP although it did not antagonize the contraction produced by carbachol. Treatment of detrusor strips with 1.5 mM ATP depressed the frequency response curve in field stimulated tissues. This depression was additive with that produced by atropine. In the present experiments indomethacin did not significantly augment the effect of desensitization with ATP. It is suggested that the atropine-resistant neurotransmission in rabbit detrusor may involve both ATP and PGs acting in cooperation.", "contents": "Interaction of prostaglandins and adenosine 5'-triphosphate in the noncholinergic neurotransmission in rabbit detrusor. Part of the excitatory transmission in rabbit detrusor is noncholinergic and nonadrenergic, and prostaglandins (PGs) and adenosine 5'-triphosphate (ATP) have been implicated in this transmission. The present experiments investigate the possibility of an interaction between PGs and ATP in rabbit detrusor. Indomethacin (2.8 muM) depressed the contraction produced by ATP although it did not antagonize the contraction produced by carbachol. Treatment of detrusor strips with 1.5 mM ATP depressed the frequency response curve in field stimulated tissues. This depression was additive with that produced by atropine. In the present experiments indomethacin did not significantly augment the effect of desensitization with ATP. It is suggested that the atropine-resistant neurotransmission in rabbit detrusor may involve both ATP and PGs acting in cooperation."}
{"id": "PMID:212796", "title": "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 analog development. An active anthracycline devoid of cardiotoxicity; a bleomycin with no effect on pulmonary tissue; an analog of streptozotocin devoid of nephrotoxicity; these would be advances of inestimable benefit to the cancer patient of the future.", "contents": "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 analog development. An active anthracycline devoid of cardiotoxicity; a bleomycin with no effect on pulmonary tissue; an analog of streptozotocin devoid of nephrotoxicity; these would be advances of inestimable benefit to the cancer patient of the future."}
{"id": "PMID:212797", "title": "Observations on the neuromuscular blocking action of alcuronium in the dog and its reversal by neostigmine.", "content": "The action of alcuronium chloride on neuromuscular transmission in the dogs was investigated by electrical and mechanical methods. The mean duration of action was 70 min. Reversal of its action was produced with atropine and neostigmine.", "contents": "Observations on the neuromuscular blocking action of alcuronium in the dog and its reversal by neostigmine. The action of alcuronium chloride on neuromuscular transmission in the dogs was investigated by electrical and mechanical methods. The mean duration of action was 70 min. Reversal of its action was produced with atropine and neostigmine."}
{"id": "PMID:212798", "title": "The resistance to reinfection of tracheal organ cultures from chickens previously infected with avian infections bronchitis virus.", "content": "Lower titres of avian infectious bronchitis (AIB) virus were found following the infection of tracheal organ cultures prepared from chickens that had been given AIB virus intranasally six weeks previously than were found following the infection of organ cultures prepared from untreated or from passively-immune chickens. No infectious virus was found in the tracheal organ cultures at the time they were prepared.", "contents": "The resistance to reinfection of tracheal organ cultures from chickens previously infected with avian infections bronchitis virus. Lower titres of avian infectious bronchitis (AIB) virus were found following the infection of tracheal organ cultures prepared from chickens that had been given AIB virus intranasally six weeks previously than were found following the infection of organ cultures prepared from untreated or from passively-immune chickens. No infectious virus was found in the tracheal organ cultures at the time they were prepared."}
{"id": "PMID:212799", "title": "The experimental infection of piglets with a porcine reovirus.", "content": "A strain (Quebec) of reovirus isolated from the faeces of a pig with dysentery was neutralised by reovirus type 1 antiserum. Four of eight hysterectomy-produced, colostrum-deprived (HPCD) piglets dosed orally with the third cell culture passage of the virus developed diarrhoea and showed focal areas of villous atrophy in the small intestine. The virus was isolated from the intestinal tract of all eight specific pathogen free piglets, but not from three control animals. Nine germ-free piglets dosed orally with the eight cell culture passage of the virus showed neither clinical signs nor lesions, but virus was recovered from their intestinal tracts for 14 days after infection. No virus was isolated from four control germ-free piglets.", "contents": "The experimental infection of piglets with a porcine reovirus. A strain (Quebec) of reovirus isolated from the faeces of a pig with dysentery was neutralised by reovirus type 1 antiserum. Four of eight hysterectomy-produced, colostrum-deprived (HPCD) piglets dosed orally with the third cell culture passage of the virus developed diarrhoea and showed focal areas of villous atrophy in the small intestine. The virus was isolated from the intestinal tract of all eight specific pathogen free piglets, but not from three control animals. Nine germ-free piglets dosed orally with the eight cell culture passage of the virus showed neither clinical signs nor lesions, but virus was recovered from their intestinal tracts for 14 days after infection. No virus was isolated from four control germ-free piglets."}
{"id": "PMID:212800", "title": "Scanning electron microscope study of Sendai virus fusion between HeLa cells and chick erythrocytes.", "content": "Chick erythrocytes were fused with HeLa cells by Sendai virus and preparations examined by scanning electron microscopy at different times after fusion. Heterokaryons were usually formed by fusion of erythrocyte ghosts with HeLa cells. Occasionally whole erythrocytes were engulfed but there was no evidence that free nuclei fused. Initial inter-cell attachments were usually, and possibly always, made at the site of an attached virus particle. This study helps to correlate topographical findings with previous two-dimensional studies with the transmission electron microscope and may also provide a model system for the fusion of parasitised erythrocytes with eukaryotic cells.", "contents": "Scanning electron microscope study of Sendai virus fusion between HeLa cells and chick erythrocytes. Chick erythrocytes were fused with HeLa cells by Sendai virus and preparations examined by scanning electron microscopy at different times after fusion. Heterokaryons were usually formed by fusion of erythrocyte ghosts with HeLa cells. Occasionally whole erythrocytes were engulfed but there was no evidence that free nuclei fused. Initial inter-cell attachments were usually, and possibly always, made at the site of an attached virus particle. This study helps to correlate topographical findings with previous two-dimensional studies with the transmission electron microscope and may also provide a model system for the fusion of parasitised erythrocytes with eukaryotic cells."}
{"id": "PMID:212806", "title": "The recruitment times and firing patterns of the medullary respiratory neurones of the cat.", "content": "The brainstem of anaesthetized cats was explored for respiratory neurones with microelectrodes in the regions of the nucleus retroambigualis (ventrolateral region) and the nucleus tractus solitarius (dorsomedial region). These neurones were analysed with respect to their firing patterns and recruitment times, as referenced to the respiratory cycle. All of the respiratory neurones showed a stable and ordered pattern of firing. Four groups of neurones with similar characteristics within each group, but differing from each other, were statistically examined; the inspiratory neurones of the dorsomedial region, the 'late' inspiratory neurones of the ventrolateral region, the 'early' inspiratory neurones of the ventrolateral region and the expiratory neurones of the ventrolateral region.", "contents": "The recruitment times and firing patterns of the medullary respiratory neurones of the cat. The brainstem of anaesthetized cats was explored for respiratory neurones with microelectrodes in the regions of the nucleus retroambigualis (ventrolateral region) and the nucleus tractus solitarius (dorsomedial region). These neurones were analysed with respect to their firing patterns and recruitment times, as referenced to the respiratory cycle. All of the respiratory neurones showed a stable and ordered pattern of firing. Four groups of neurones with similar characteristics within each group, but differing from each other, were statistically examined; the inspiratory neurones of the dorsomedial region, the 'late' inspiratory neurones of the ventrolateral region, the 'early' inspiratory neurones of the ventrolateral region and the expiratory neurones of the ventrolateral region."}
{"id": "PMID:212813", "title": "[Clinical studies of the role of the fluorescent circulating antibody test in the diagnosis of active tuberculosis].", "content": "The value was studied, of the test of circulating fluorescent antibodies against M. tuberculosis in establishing the diagnosis of active tuberculosis in 610 patients classified in 4 groups: 1. active tuberculosis bacteriologically confirmed; 2. active tuberculosis with negative bacteriological examination, but confirmed by other methods of criteria; 3. stabilized tuberculosis; 4. non-tuberculous affections. The specificity of the test in active tuberculosis was of 80% in adults and of 91,5% in children. The test was negative in 80,3% of stabilized tuberculosis cases and in 69% of non-tuberculous affections. The sensitivity was lower in active tuberculosis with positive bacilloscopy (67%) against active tuberculosis with negative bacilloscopy (90,6%), a fact explained by a high consumption of anti-bacillary antibodies, demonstrated by positivation of the test when bacilloscopy becomes negative. The use of the test is indicated in establishing a therapeutic test, and in the context of clinical and radiologic explorations, as well as in the expertising of working capacities of previous tuberculosis patients.", "contents": "[Clinical studies of the role of the fluorescent circulating antibody test in the diagnosis of active tuberculosis]. The value was studied, of the test of circulating fluorescent antibodies against M. tuberculosis in establishing the diagnosis of active tuberculosis in 610 patients classified in 4 groups: 1. active tuberculosis bacteriologically confirmed; 2. active tuberculosis with negative bacteriological examination, but confirmed by other methods of criteria; 3. stabilized tuberculosis; 4. non-tuberculous affections. The specificity of the test in active tuberculosis was of 80% in adults and of 91,5% in children. The test was negative in 80,3% of stabilized tuberculosis cases and in 69% of non-tuberculous affections. The sensitivity was lower in active tuberculosis with positive bacilloscopy (67%) against active tuberculosis with negative bacilloscopy (90,6%), a fact explained by a high consumption of anti-bacillary antibodies, demonstrated by positivation of the test when bacilloscopy becomes negative. The use of the test is indicated in establishing a therapeutic test, and in the context of clinical and radiologic explorations, as well as in the expertising of working capacities of previous tuberculosis patients."}
{"id": "PMID:212815", "title": "[Studies of resumption of treatment with rifampin and ethambutol in patients with recurrent pulmonary tuberculosis].", "content": "The immediate and the late results are analyzed, of resumption of treatment with RMP and EMB in 50 patients with relapsing pulmonary tuberculosis that had not been treated with these drugs previously. After the first year of treatment negativation of the sputum by microscopy and culture was obtained in 45 of the patients, while 5 remained still positive. In the following two years 7 of the negative patients became positive again and finally 8 were solved completely and 4 became chronically ill. The most important of the unfavourable factors were simultaneous radiological and bacteriological relapses and chronic alcoholism. There was no primary or secondary resistance against the drugs used in the treatment. Intolerance to the drugs, although frequent, did not significantly affect the course of the treatment, especially because it occurred only at a later time.", "contents": "[Studies of resumption of treatment with rifampin and ethambutol in patients with recurrent pulmonary tuberculosis]. The immediate and the late results are analyzed, of resumption of treatment with RMP and EMB in 50 patients with relapsing pulmonary tuberculosis that had not been treated with these drugs previously. After the first year of treatment negativation of the sputum by microscopy and culture was obtained in 45 of the patients, while 5 remained still positive. In the following two years 7 of the negative patients became positive again and finally 8 were solved completely and 4 became chronically ill. The most important of the unfavourable factors were simultaneous radiological and bacteriological relapses and chronic alcoholism. There was no primary or secondary resistance against the drugs used in the treatment. Intolerance to the drugs, although frequent, did not significantly affect the course of the treatment, especially because it occurred only at a later time."}
{"id": "PMID:212821", "title": "Serologic markers of hepatitis A and B in chronic active hepatitis.", "content": "Sera from 44 patients with a well-documented diagnosis of chronic active hepatitis (CAH) were analysed for antibodies to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAg) and anti-HBs, e-antigen (HBeAg) and anti-HBe, as well as antibodies to hepatitis B core antigen (anti-HBc). Twenty-two patients had serologic evidence of hepatitis A infection. The frequency of anti-HAV was low in patients under 50 years of age (21%) but high among older patients (72%). There was, however, no significant difference between patients and age-matched controls regarding the prevalence of anti-HAV in serum. Markers for hepatitis B virus were found in 10 patients or 23% as compared with about 10% in Swedish blood donors. The results indicate that hepatitis A virus is of little importance in the pathogenesis of CAH and confirm the association between hepatitis B virus and development of chronic active hepatitis.", "contents": "Serologic markers of hepatitis A and B in chronic active hepatitis. Sera from 44 patients with a well-documented diagnosis of chronic active hepatitis (CAH) were analysed for antibodies to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAg) and anti-HBs, e-antigen (HBeAg) and anti-HBe, as well as antibodies to hepatitis B core antigen (anti-HBc). Twenty-two patients had serologic evidence of hepatitis A infection. The frequency of anti-HAV was low in patients under 50 years of age (21%) but high among older patients (72%). There was, however, no significant difference between patients and age-matched controls regarding the prevalence of anti-HAV in serum. Markers for hepatitis B virus were found in 10 patients or 23% as compared with about 10% in Swedish blood donors. The results indicate that hepatitis A virus is of little importance in the pathogenesis of CAH and confirm the association between hepatitis B virus and development of chronic active hepatitis."}
{"id": "PMID:212822", "title": "Human leucocyte migration inhibitory factor (LIF). V. Specific regulation of the lymphokine serine protease activity by 3',5'-cGMP and, possibly, 2',3'-cCMP.", "content": "The cyclic nucleotides guanosine 3',5'-cyclic monophosphoric acid (3',5'-cGMP) and cytidine 2',3'-cyclic monophosphoric acid (2',3'-cCMP) but not cyclic phosphodiesters derived from the bases adenine and uracil preserved LIF activity against the blocking effect of the serine protease inhibitor phenylmethylsulphonyl fluoride (PMSF). Phosphomonoesters derived from guanosine and cytidine as well as 2',3'-cGMP and 3',5'-cCMP were all inactive, indicating specificity for phosphodiester bonds and their respective positions in the two active nucleotides. The protection afforded by 3',5'-cGMP and 2',3'-cCMP was dose dependent. Thus, using 10(-3) M PMSF, 3',5'-cGMP was active at concentrations higher than 10(-5) to 10(-4) M, and 2',3'-cCMP at concentrations higher than 3 X 10(-4) to 10(-3) M. The more pronounced LIF-inhibitory effect obtained by increased concentrations of PMSF could be overcome by raising the levels of the nucleotides, indicating that the interactions between PMSF and the nucleotides with LIF were mutally exclusive. The possibility that 3',5'-cGMP and perhaps 2',3'-cCMP function as modulators of LIF is discussed, and models for the function of this lymphokine are proposed.", "contents": "Human leucocyte migration inhibitory factor (LIF). V. Specific regulation of the lymphokine serine protease activity by 3',5'-cGMP and, possibly, 2',3'-cCMP. The cyclic nucleotides guanosine 3',5'-cyclic monophosphoric acid (3',5'-cGMP) and cytidine 2',3'-cyclic monophosphoric acid (2',3'-cCMP) but not cyclic phosphodiesters derived from the bases adenine and uracil preserved LIF activity against the blocking effect of the serine protease inhibitor phenylmethylsulphonyl fluoride (PMSF). Phosphomonoesters derived from guanosine and cytidine as well as 2',3'-cGMP and 3',5'-cCMP were all inactive, indicating specificity for phosphodiester bonds and their respective positions in the two active nucleotides. The protection afforded by 3',5'-cGMP and 2',3'-cCMP was dose dependent. Thus, using 10(-3) M PMSF, 3',5'-cGMP was active at concentrations higher than 10(-5) to 10(-4) M, and 2',3'-cCMP at concentrations higher than 3 X 10(-4) to 10(-3) M. The more pronounced LIF-inhibitory effect obtained by increased concentrations of PMSF could be overcome by raising the levels of the nucleotides, indicating that the interactions between PMSF and the nucleotides with LIF were mutally exclusive. The possibility that 3',5'-cGMP and perhaps 2',3'-cCMP function as modulators of LIF is discussed, and models for the function of this lymphokine are proposed."}
{"id": "PMID:212818", "title": "99mTc-pyrophosphate kinetics in man (relationship between bone uptake and mineral content).", "content": "Both the kinetics and the regional distribution of 99mTc-PPi were studied in the skeleton of healthy subjects of various ages by surface counting using a scintillation counter placed over different skeletal areas. The results were compared with bone mineral content as determined by the photonic absorption technique. Kinetic data of bone uptake were obtained by subtracting the counts measured in blood from the counts recorded over each body surface after making proportional corrections. The surface-counting patterns show a higher generalized 99mTc-PPi bone uptake in children and adolescents than in adults. The relative regional distribution of the tracer shows no difference between the two groups. The tracer accumulated more rapidly in spongy bone than in compact bone, and the fixation process was carried out during the first 30 min for both spongy and compact bone. In youths, however, higher uptake values corresponded to lower values of mineral content. The findings enable the normal surface-counting pattern to be constructed and confirm that the 99mTc-PPi uptake is related to bone metabolism; they also suggest the application of external measurements for the study of metabolic bone diseases.", "contents": "99mTc-pyrophosphate kinetics in man (relationship between bone uptake and mineral content). Both the kinetics and the regional distribution of 99mTc-PPi were studied in the skeleton of healthy subjects of various ages by surface counting using a scintillation counter placed over different skeletal areas. The results were compared with bone mineral content as determined by the photonic absorption technique. Kinetic data of bone uptake were obtained by subtracting the counts measured in blood from the counts recorded over each body surface after making proportional corrections. The surface-counting patterns show a higher generalized 99mTc-PPi bone uptake in children and adolescents than in adults. The relative regional distribution of the tracer shows no difference between the two groups. The tracer accumulated more rapidly in spongy bone than in compact bone, and the fixation process was carried out during the first 30 min for both spongy and compact bone. In youths, however, higher uptake values corresponded to lower values of mineral content. The findings enable the normal surface-counting pattern to be constructed and confirm that the 99mTc-PPi uptake is related to bone metabolism; they also suggest the application of external measurements for the study of metabolic bone diseases."}
{"id": "PMID:212823", "title": "Effect of cyclic nucleotides, isoproterenol and cholera toxin on DNA synthesis triggered by mitogens.", "content": "The effect of cyclic nucleotides, isoproterenol and cholera toxin on phytohaemagglutinin (PHA), concanavalin A (Con A) and anti-allotype-induced rabbit lymphoid cell proliferation was examined. Cholera toxin in concentrations ranging from 10(-8) microgram to 1 microgram per culture inhibited DNA synthesis, triggered by PHA, Con A and nocardia water-soluble mitogen (NWSM). It had the opposite effect on stimulation with antibodies directed against allotypic specificities of the immunoglobulin light chains: over the entire range of tested concentrations, cholera toxin stimulated DNA synthesis triggered by antibodies to Ab4, Ab5, Ab9 and to Aa1 allotypic specificities. Relatively high concentrations of dibutyryl adenosine 3':5'-cyclic monophosphate (cAMP) and isoproterenol (10(-3) M) inhibited mitogen-stimulated thymidine incorporation; lower concentrations (10(-9) M) had an enhancing effect. A similar enhancing effect was observed when high (10(-3) M) concentrations of dibutyryl guanosine 3':5'-cyclic monophosphate (cGMP) were used.", "contents": "Effect of cyclic nucleotides, isoproterenol and cholera toxin on DNA synthesis triggered by mitogens. The effect of cyclic nucleotides, isoproterenol and cholera toxin on phytohaemagglutinin (PHA), concanavalin A (Con A) and anti-allotype-induced rabbit lymphoid cell proliferation was examined. Cholera toxin in concentrations ranging from 10(-8) microgram to 1 microgram per culture inhibited DNA synthesis, triggered by PHA, Con A and nocardia water-soluble mitogen (NWSM). It had the opposite effect on stimulation with antibodies directed against allotypic specificities of the immunoglobulin light chains: over the entire range of tested concentrations, cholera toxin stimulated DNA synthesis triggered by antibodies to Ab4, Ab5, Ab9 and to Aa1 allotypic specificities. Relatively high concentrations of dibutyryl adenosine 3':5'-cyclic monophosphate (cAMP) and isoproterenol (10(-3) M) inhibited mitogen-stimulated thymidine incorporation; lower concentrations (10(-9) M) had an enhancing effect. A similar enhancing effect was observed when high (10(-3) M) concentrations of dibutyryl guanosine 3':5'-cyclic monophosphate (cGMP) were used."}
{"id": "PMID:212824", "title": "Effects of some connective-tissue active drugs on protocollagen proline hydroxylase activity.", "content": "The effect on protocollagen proline hydroxylase of drugs reported to be capable of inducing the lupus erythematosus syndrome and in some way acting on connective tissue and inflammation was studied in an in vitro system for the hydroxylation of 14C-Pro-labelled protocollagen. Some derivatives were also studied. It was found that benzoic acid and phenothiazine derivatives, hydroxyphenols, (+)catechin, beta-amino propionitrile, certain B vitamins, dihydrazinophthalazine, cysteine and dimethylcysteine were inhibitors of PPH. The chelation of Fe2+ions by the compounds mentioned is suggested to be essential.", "contents": "Effects of some connective-tissue active drugs on protocollagen proline hydroxylase activity. The effect on protocollagen proline hydroxylase of drugs reported to be capable of inducing the lupus erythematosus syndrome and in some way acting on connective tissue and inflammation was studied in an in vitro system for the hydroxylation of 14C-Pro-labelled protocollagen. Some derivatives were also studied. It was found that benzoic acid and phenothiazine derivatives, hydroxyphenols, (+)catechin, beta-amino propionitrile, certain B vitamins, dihydrazinophthalazine, cysteine and dimethylcysteine were inhibitors of PPH. The chelation of Fe2+ions by the compounds mentioned is suggested to be essential."}
{"id": "PMID:212825", "title": "Effect of occupational exposure to organophosphorus insecticides on neuromuscular function.", "content": "Neurophysiological investigations and determinations of cholinesterase activity on plasma and erythrocytes were carried out on 11 Swedish spraymen exposed to bromophos, diazinon, dursbane, and malathion. Plasma cholinesterase activity was significantly reduced after work, while erythrocyte cholinesterase activity was unchanged. In none of the workers with a decreased plasma cholinesterase activity after work could any related acute neuromuscular disturbance be detected when the men were tested with repetitive nerve stimulation and with single fiber electromyography. Signs of subclinical neuropathy were present as a slight reduction in sensory conduction velocity and increased fiber density in some workers.", "contents": "Effect of occupational exposure to organophosphorus insecticides on neuromuscular function. Neurophysiological investigations and determinations of cholinesterase activity on plasma and erythrocytes were carried out on 11 Swedish spraymen exposed to bromophos, diazinon, dursbane, and malathion. Plasma cholinesterase activity was significantly reduced after work, while erythrocyte cholinesterase activity was unchanged. In none of the workers with a decreased plasma cholinesterase activity after work could any related acute neuromuscular disturbance be detected when the men were tested with repetitive nerve stimulation and with single fiber electromyography. Signs of subclinical neuropathy were present as a slight reduction in sensory conduction velocity and increased fiber density in some workers."}
{"id": "PMID:212826", "title": "[Immunosuppression as a concomitant effect].", "content": "1. It is becoming increasingly clear that besides traditional immunosuppressive agents, an array of miscellaneous influences and conditions, as well as drugs used for other purposes, can affect the immune system. The potential pathogenetic role of immunity in an ever growing number of diseases, including infections, cancer, and autoimmune processes, confers on the concept of concomitant immunosuppression or immunotoxicology its due place in the discipline of immunopharmacology. 2. Microorganisms such as viruses, bacteria, and protozoa (and their products), as well as parasites, may depress immune reactivity. The mechanism of action, dose-response dependency, effect of timing, and relation to bacterial adjuvanticity need more thorough exploration. 3. The efficacy of immunosuppressive drug protocols can be improved by combining immunosuppressants without bone marrow toxicity, such as niridazole or free fatty acids, with the standard antiproliferative immunosuppressive agents. 4. Prostaglandin is a likely candidate for an essential role as an immunosuppressive effector. Its release from T-suppressor cells is triggered for example by microorganisms. Moreover, dietetic and metabolic factors, such as free fatty acids, and nervous impulses affect prostaglandin formation. If thus constitutes a link between the nervous system and, on the other hand, immunity and possibly cancer.", "contents": "[Immunosuppression as a concomitant effect]. 1. It is becoming increasingly clear that besides traditional immunosuppressive agents, an array of miscellaneous influences and conditions, as well as drugs used for other purposes, can affect the immune system. The potential pathogenetic role of immunity in an ever growing number of diseases, including infections, cancer, and autoimmune processes, confers on the concept of concomitant immunosuppression or immunotoxicology its due place in the discipline of immunopharmacology. 2. Microorganisms such as viruses, bacteria, and protozoa (and their products), as well as parasites, may depress immune reactivity. The mechanism of action, dose-response dependency, effect of timing, and relation to bacterial adjuvanticity need more thorough exploration. 3. The efficacy of immunosuppressive drug protocols can be improved by combining immunosuppressants without bone marrow toxicity, such as niridazole or free fatty acids, with the standard antiproliferative immunosuppressive agents. 4. Prostaglandin is a likely candidate for an essential role as an immunosuppressive effector. Its release from T-suppressor cells is triggered for example by microorganisms. Moreover, dietetic and metabolic factors, such as free fatty acids, and nervous impulses affect prostaglandin formation. If thus constitutes a link between the nervous system and, on the other hand, immunity and possibly cancer."}
{"id": "PMID:212827", "title": "[Practical value of new knowledge on the structure and function of pituitary adenomas].", "content": "The usual classification of pituitary adenomas into eosinophilic, basophilic, and chromophobe types is no longer sufficient to correlate the histologic findings with the increasing number of clinical syndromes described in recent years. Some histologic forms are observed in several clinical syndromes, whereas some clinical entities may be caused by several histologic types. A new classification is mandatory. Recent endocrine, ultrastructural and histo-immunologic research has shown that the endocrine inactive adenoma, which has usually been related to the \"chromophobe\" adenoma, represents only a small group of the pituitary neoplasms. A more critical evaluation shows that 3 out of 4 patients present clinical or endocrine signs and findings of increased hormone secretion. Several authors have therefore suggested that pituitary adenomas be classified according to their secretory characteristics, which can be determined either by clinical and endocrine examination or by immunohistology and electron microscopy. Abnormally increased hormone secretion allows early detection of the neoplasm when the remaining normal gland is still able to recover its normal function and the endocrine symptoms therefore are fully reversible. The therapy of pituitary adenomas must normalize the hormone hypersecretion without causing new endocrine deficits, and must at the same time reverse neurological compression symptoms. The treatment may be either surgical excision, irradiation, medical inhibition of abnormal secretion, substitution of insufficient hormones or a combination of these methods. The prognosis of the endocrine symptoms is significantly better in small adenomas and full restoration of sexual function is even observed in an increasing number of patients.", "contents": "[Practical value of new knowledge on the structure and function of pituitary adenomas]. The usual classification of pituitary adenomas into eosinophilic, basophilic, and chromophobe types is no longer sufficient to correlate the histologic findings with the increasing number of clinical syndromes described in recent years. Some histologic forms are observed in several clinical syndromes, whereas some clinical entities may be caused by several histologic types. A new classification is mandatory. Recent endocrine, ultrastructural and histo-immunologic research has shown that the endocrine inactive adenoma, which has usually been related to the \"chromophobe\" adenoma, represents only a small group of the pituitary neoplasms. A more critical evaluation shows that 3 out of 4 patients present clinical or endocrine signs and findings of increased hormone secretion. Several authors have therefore suggested that pituitary adenomas be classified according to their secretory characteristics, which can be determined either by clinical and endocrine examination or by immunohistology and electron microscopy. Abnormally increased hormone secretion allows early detection of the neoplasm when the remaining normal gland is still able to recover its normal function and the endocrine symptoms therefore are fully reversible. The therapy of pituitary adenomas must normalize the hormone hypersecretion without causing new endocrine deficits, and must at the same time reverse neurological compression symptoms. The treatment may be either surgical excision, irradiation, medical inhibition of abnormal secretion, substitution of insufficient hormones or a combination of these methods. The prognosis of the endocrine symptoms is significantly better in small adenomas and full restoration of sexual function is even observed in an increasing number of patients."}
{"id": "PMID:212828", "title": "[Urinary excretion kinetics of enzymes and proteins in the application of therapeutic doses of gentamycin].", "content": "9 patients with chronic pyelonephritis were given gentamicin intramuscularly in an appropriate dosage for a period of 10 days. The urinary excretion of cells, protein, alanine aminopeptidase (EC 3.4.11.2),N-acetylglucosaminidase(EC 3.2.1.30) and alpha-galactosidase (EC 3.2.1.23) was determined daily. The most striking enzyme increase occurred in alanine aminopeptidase. The enzyme and protein output appears to be rhythmic and discontinuous. A 2--3-day rhythm is suggested. Rhythmic alterations of the digestion activity of the lysosomes are assumed to be the cause of these changes.", "contents": "[Urinary excretion kinetics of enzymes and proteins in the application of therapeutic doses of gentamycin]. 9 patients with chronic pyelonephritis were given gentamicin intramuscularly in an appropriate dosage for a period of 10 days. The urinary excretion of cells, protein, alanine aminopeptidase (EC 3.4.11.2),N-acetylglucosaminidase(EC 3.2.1.30) and alpha-galactosidase (EC 3.2.1.23) was determined daily. The most striking enzyme increase occurred in alanine aminopeptidase. The enzyme and protein output appears to be rhythmic and discontinuous. A 2--3-day rhythm is suggested. Rhythmic alterations of the digestion activity of the lysosomes are assumed to be the cause of these changes."}
{"id": "PMID:212829", "title": "[A case of poliomyelitis type 1 in Switzerland in a non-vaccinated child].", "content": "A case of paralytic poliomyelitis in an unvaccinated child is reported. Besides clinical aspects, special interest is focused on immunological and virological findings. Paralytic disease in temporal connection with poliomyelitis vaccination is also discussed.", "contents": "[A case of poliomyelitis type 1 in Switzerland in a non-vaccinated child]. A case of paralytic poliomyelitis in an unvaccinated child is reported. Besides clinical aspects, special interest is focused on immunological and virological findings. Paralytic disease in temporal connection with poliomyelitis vaccination is also discussed."}
{"id": "PMID:212831", "title": "Carcinogenicity testing of chemicals with particular reference to organochlorine pesticides.", "content": "The organochlorine chemicals comprise a large number of pesticides that are used widely throughout the world. The organochlorine pesticides given in the diet to mice are carcinogenic for the liver. They induce not only carcinomas of the liver, particularly at the higher doses, but also carcinomas and sarcomas in other organs in rats. They cause acute and chronic liver and kidney injury, which interferes with the development of carcinomas and sarcomas in rats. The testing of chemicals for carcinogenicity, with particular reference to organochlorine pesticides, includes discussions on the following topics: classification of hepatic lesions in mice and rats, toxicity versus carcinogenicity in the testing of chemicals, a comparison of carcinomas and cirrhosis of the liver in experimental animals and humans, and the significance of laboratory carcinogenicity findings to human health.", "contents": "Carcinogenicity testing of chemicals with particular reference to organochlorine pesticides. The organochlorine chemicals comprise a large number of pesticides that are used widely throughout the world. The organochlorine pesticides given in the diet to mice are carcinogenic for the liver. They induce not only carcinomas of the liver, particularly at the higher doses, but also carcinomas and sarcomas in other organs in rats. They cause acute and chronic liver and kidney injury, which interferes with the development of carcinomas and sarcomas in rats. The testing of chemicals for carcinogenicity, with particular reference to organochlorine pesticides, includes discussions on the following topics: classification of hepatic lesions in mice and rats, toxicity versus carcinogenicity in the testing of chemicals, a comparison of carcinomas and cirrhosis of the liver in experimental animals and humans, and the significance of laboratory carcinogenicity findings to human health."}
{"id": "PMID:212833", "title": "Invertebrate collagens.", "content": "The collagens of all major invertebrate phyla have been studied, but characterization has been thorough in only a few classes and in no case in the detail (such as sequence analysis) known for vertebrate collagen. Biochemical data on insect collagen are particularly sparse. Invertebrate and vertebrate collagens are strikingly similar, with some notably unique features in annelids and nematodes. Present data do not support the suggestion that invertebrate collagens resemble vertebrate basement membrane collagen. In invertebrates, as in vertebrates, collagens of specific tissues show differenes that probably reflect individual tissue requirements.", "contents": "Invertebrate collagens. The collagens of all major invertebrate phyla have been studied, but characterization has been thorough in only a few classes and in no case in the detail (such as sequence analysis) known for vertebrate collagen. Biochemical data on insect collagen are particularly sparse. Invertebrate and vertebrate collagens are strikingly similar, with some notably unique features in annelids and nematodes. Present data do not support the suggestion that invertebrate collagens resemble vertebrate basement membrane collagen. In invertebrates, as in vertebrates, collagens of specific tissues show differenes that probably reflect individual tissue requirements."}
{"id": "PMID:212834", "title": "Silicosis in kaolin workers and firebrick makers.", "content": "Nine patients with disabling pneumoconiosis were selected over a three-year period for study because of a work history of kaolin exposure. All had worked in the Missouri firebrick industry. Chest roentgenograms from all nine and lung tissue from two  were consistent with silicosis. Worksite analysis of airborne dust at several Missouri firebrick factories revealed that some current workers are exposed to both free silica (up to 4.5%) and cristobalite (up to 8.9%) at levels exceeding the threshold limit value (TLV). Analysis of airborne dust from several kaolin processing plants in South Carolina and Georgia revealed that a few workers are exposed to about 1% free silica at levels occasionally exceeding the TVL. We conclude that silicosis is a serious risk for Missouri kaolin workers and a potential risk for workers in South Carolina and Georgia. A prevalence survey is needed in Missouri to assess the problem.", "contents": "Silicosis in kaolin workers and firebrick makers. Nine patients with disabling pneumoconiosis were selected over a three-year period for study because of a work history of kaolin exposure. All had worked in the Missouri firebrick industry. Chest roentgenograms from all nine and lung tissue from two  were consistent with silicosis. Worksite analysis of airborne dust at several Missouri firebrick factories revealed that some current workers are exposed to both free silica (up to 4.5%) and cristobalite (up to 8.9%) at levels exceeding the threshold limit value (TLV). Analysis of airborne dust from several kaolin processing plants in South Carolina and Georgia revealed that a few workers are exposed to about 1% free silica at levels occasionally exceeding the TVL. We conclude that silicosis is a serious risk for Missouri kaolin workers and a potential risk for workers in South Carolina and Georgia. A prevalence survey is needed in Missouri to assess the problem."}
{"id": "PMID:212837", "title": "Initial characterization of Trypanosoma lewisi surface membrane antigen.", "content": "The purified T. lewisi were subjected to hypotonic lysis plus freezing and thawing in acetone dry ice bath. The trypanosome ghosts were obtained after repeated washing and centrifugation. The homogenized ghost suspension was assayed for enzyme Na++K+ ATPase activity to ratify the presence of the trypanosome surface membrane. Membrane solubilized in sodium dodecyl sulfate were fractionated by gel filtration on Sephadex columns equilibrated with the detergent and electrophoresis in polyacrylamide gel. Crude trypanosome surface membrane antigens were tested for their immunogenicity, administered to rats in Fraund's complete adjuvant. The results of these experiments indicated that the protective immunogen is tightly bound to the membrane since the use of strong anionic detergent is necessary in its extraction.", "contents": "Initial characterization of Trypanosoma lewisi surface membrane antigen. The purified T. lewisi were subjected to hypotonic lysis plus freezing and thawing in acetone dry ice bath. The trypanosome ghosts were obtained after repeated washing and centrifugation. The homogenized ghost suspension was assayed for enzyme Na++K+ ATPase activity to ratify the presence of the trypanosome surface membrane. Membrane solubilized in sodium dodecyl sulfate were fractionated by gel filtration on Sephadex columns equilibrated with the detergent and electrophoresis in polyacrylamide gel. Crude trypanosome surface membrane antigens were tested for their immunogenicity, administered to rats in Fraund's complete adjuvant. The results of these experiments indicated that the protective immunogen is tightly bound to the membrane since the use of strong anionic detergent is necessary in its extraction."}
{"id": "PMID:212839", "title": "Prospects of vaccines against cancer in man.", "content": "Preventive immunization is the cheapest and most effective approach to the management of epidemic disease. Certain forms of cancer, including Burkitt's lymphoma, carcinoma of the cervix, primary liver cancer, acute leukaemia and breast cancer show many characteristics of epidemic disease, and the possibility of producing preventive vaccine against these conditions merits serious consideration.", "contents": "Prospects of vaccines against cancer in man. Preventive immunization is the cheapest and most effective approach to the management of epidemic disease. Certain forms of cancer, including Burkitt's lymphoma, carcinoma of the cervix, primary liver cancer, acute leukaemia and breast cancer show many characteristics of epidemic disease, and the possibility of producing preventive vaccine against these conditions merits serious consideration."}
{"id": "PMID:212842", "title": "Glomus jugulare tumour in a dog; a case report.", "content": "Unilateral ataxia of the head and trunk and right-sided paralysis of the trigeminal, facial, and hypoglossal nerves were the major neurologic dysfunctions in a nine-year-old male French bulldog. These symptoms together with the results of radiologic examination and bone scintigraphy pointed to a cranial base tumour on the right side. The tumour was histologically identified as a glomus jugulare tumour. A tumour of the right carotid body and a seminoma in the right testicle were additional findings at autopsy.", "contents": "Glomus jugulare tumour in a dog; a case report. Unilateral ataxia of the head and trunk and right-sided paralysis of the trigeminal, facial, and hypoglossal nerves were the major neurologic dysfunctions in a nine-year-old male French bulldog. These symptoms together with the results of radiologic examination and bone scintigraphy pointed to a cranial base tumour on the right side. The tumour was histologically identified as a glomus jugulare tumour. A tumour of the right carotid body and a seminoma in the right testicle were additional findings at autopsy."}
{"id": "PMID:212845", "title": "The lipid-chemical features of the metastatic tissues into the liver from the human gastric cancer, large intestinal cancer and malignant insulinoma.", "content": "In order to clarify the biochemical features of metastatic tissues into the liver of human cancerous cells, 12 of primary cancerous tissues and 3 of metastatic tissues of the large intestinal cancer, 6 of primary cancerous tissues and 2 of metastatic tissues of the gastric cancer, and 3 of primary cancerous tissues and 3 of metastatic tissues of malignant insulinoma were studied lipid-chemically. Cancerous tissues and metastatic tissues into the liver were collected by biopsy or surgical operation. From each tissue, the total lipid was extracted and one part of the total lipid was separated into phospholipid and triglyceride by TLC. Then, the fatty acid composition and the fatty acid content of each lipid fraction were measured by GLC. The most remarkable findings were recognized in the phospholipid fatty acid composition of the tissues. Namely, the percentage values of C14:0 and C16:1 were larger and that of C20:4 was smaller in metastatic tissues than those of gastric primary lesions. As for the large intestinal cancer, the percentage value of C18:1 was smaller and that of C18:2 larger in metastatic tissues than those of primary lesions. In the malignant insulinoma, the percentage value of C18:0 was larger in metastatic tissues than that of the primary lesions.", "contents": "The lipid-chemical features of the metastatic tissues into the liver from the human gastric cancer, large intestinal cancer and malignant insulinoma. In order to clarify the biochemical features of metastatic tissues into the liver of human cancerous cells, 12 of primary cancerous tissues and 3 of metastatic tissues of the large intestinal cancer, 6 of primary cancerous tissues and 2 of metastatic tissues of the gastric cancer, and 3 of primary cancerous tissues and 3 of metastatic tissues of malignant insulinoma were studied lipid-chemically. Cancerous tissues and metastatic tissues into the liver were collected by biopsy or surgical operation. From each tissue, the total lipid was extracted and one part of the total lipid was separated into phospholipid and triglyceride by TLC. Then, the fatty acid composition and the fatty acid content of each lipid fraction were measured by GLC. The most remarkable findings were recognized in the phospholipid fatty acid composition of the tissues. Namely, the percentage values of C14:0 and C16:1 were larger and that of C20:4 was smaller in metastatic tissues than those of gastric primary lesions. As for the large intestinal cancer, the percentage value of C18:1 was smaller and that of C18:2 larger in metastatic tissues than those of primary lesions. In the malignant insulinoma, the percentage value of C18:0 was larger in metastatic tissues than that of the primary lesions."}
{"id": "PMID:212848", "title": "Action of dihydroaflatoxins on rat liver mitochondria. 1. Membrane-dependent osmotic and redox effects of aflatoxins B2 and G2.", "content": "Membrane-dependent osmotic and redox effects of two dihydroaflatoxins (aflatoxin B2 and G2) on isolated rat liver mitochondria were investigated. These toxins did not cause any marked swelling, inhibit any ATP induced contraction or stimulate ATPase activity of mitochondria at concentrations within the range 1--2 x 10(-6) M. Redox measurements on the respiratory chain showed that both toxins inhibited respiration between cytochrome c and the terminal oxygen. The significance of these findings in relation to the differential toxicity of the aflatoxins is discussed.", "contents": "Action of dihydroaflatoxins on rat liver mitochondria. 1. Membrane-dependent osmotic and redox effects of aflatoxins B2 and G2. Membrane-dependent osmotic and redox effects of two dihydroaflatoxins (aflatoxin B2 and G2) on isolated rat liver mitochondria were investigated. These toxins did not cause any marked swelling, inhibit any ATP induced contraction or stimulate ATPase activity of mitochondria at concentrations within the range 1--2 x 10(-6) M. Redox measurements on the respiratory chain showed that both toxins inhibited respiration between cytochrome c and the terminal oxygen. The significance of these findings in relation to the differential toxicity of the aflatoxins is discussed."}
{"id": "PMID:212849", "title": "Estrogen synthetase in choriocarcinoma cell culture. Stimulation by dibutyryl cyclic adenosine monophosphate and theophylline.", "content": "The stimulation of estrogen biosynthesis by N6,O2'--dibutyryl adenosine 3':5'-cyclic monophosphate and theophylline dbT) in cultures of the JAr line of choriocarcinoma cells was investigated by measuring the specific activity and kinetic constants of estrogen synthetase (aromatase) in the various subcellular fractions after differential centrifugation of homogenized cells in isotonic sucrose. The low speed (900xg) pellet, from cells grown with or without dbT and homogenized in isotonic sucrose, contains the majority of the aromatase activity and the highest aromatase specific activity. The aromatase specific activity in the homogenate of cells grown with dbT and in the various subcellular fractions is 4- to 10-fold higher than in cells grown without dbT. The Vmax of androstenedione (4-androstene-3,17-dione) aromatization in homogenates from dbT-stimulated cells (6.9 pmol estrogen/min per mg protein) is significantly increased over that measured in the absence of dbT (1.5 pmol estrogen/min per mg protein); the Km values, however, are not significantly different (average of 43.8nM in dbT-stimulated fractions; 53.2nM in control fractions). These results suggest that the increased aromatase specific activity in dbT-stimulated cells results from an increase in amount of active enzyme, rather than from an increase in affinity of the enzyme for its substrate.", "contents": "Estrogen synthetase in choriocarcinoma cell culture. Stimulation by dibutyryl cyclic adenosine monophosphate and theophylline. The stimulation of estrogen biosynthesis by N6,O2'--dibutyryl adenosine 3':5'-cyclic monophosphate and theophylline dbT) in cultures of the JAr line of choriocarcinoma cells was investigated by measuring the specific activity and kinetic constants of estrogen synthetase (aromatase) in the various subcellular fractions after differential centrifugation of homogenized cells in isotonic sucrose. The low speed (900xg) pellet, from cells grown with or without dbT and homogenized in isotonic sucrose, contains the majority of the aromatase activity and the highest aromatase specific activity. The aromatase specific activity in the homogenate of cells grown with dbT and in the various subcellular fractions is 4- to 10-fold higher than in cells grown without dbT. The Vmax of androstenedione (4-androstene-3,17-dione) aromatization in homogenates from dbT-stimulated cells (6.9 pmol estrogen/min per mg protein) is significantly increased over that measured in the absence of dbT (1.5 pmol estrogen/min per mg protein); the Km values, however, are not significantly different (average of 43.8nM in dbT-stimulated fractions; 53.2nM in control fractions). These results suggest that the increased aromatase specific activity in dbT-stimulated cells results from an increase in amount of active enzyme, rather than from an increase in affinity of the enzyme for its substrate."}
{"id": "PMID:212855", "title": "Malignant fibrous histiocytoma of spermatic cord.", "content": "Malignant fibrous histiocytomas are very rare, particularly those related to urogenital organs. We report herein the third known case of this entity involving the spermatic cord. Summary of the previously reported 2 cases is given with recent follow-up. Prognosis is poor.", "contents": "Malignant fibrous histiocytoma of spermatic cord. Malignant fibrous histiocytomas are very rare, particularly those related to urogenital organs. We report herein the third known case of this entity involving the spermatic cord. Summary of the previously reported 2 cases is given with recent follow-up. Prognosis is poor."}
{"id": "PMID:212858", "title": "Enzootic bovine leucosis.", "content": "Enzootic bovine leucosis is associated with infection by bovine leucosis virus. The incubation period is measured in years and a minority of infected animals develop clinical signs. The disease is widespread in Europe and elsewhere and can cause significant economic loss. The epidemiology is incompletely understood and findings from one cattle production system may not be directly applicable to another. Major control programmes exist in Denmark and West Germany and control schemes are being developed elsewhere. Eradication of enzootic bovine leucosis has been established as a goal in the EEC and research is revealing the ways in which this goal may be attained. To be effective, control and epidemiological monitoring must be interactive. Recently introduced serological tests, of improved sensitivity, provide a valuable tool.", "contents": "Enzootic bovine leucosis. Enzootic bovine leucosis is associated with infection by bovine leucosis virus. The incubation period is measured in years and a minority of infected animals develop clinical signs. The disease is widespread in Europe and elsewhere and can cause significant economic loss. The epidemiology is incompletely understood and findings from one cattle production system may not be directly applicable to another. Major control programmes exist in Denmark and West Germany and control schemes are being developed elsewhere. Eradication of enzootic bovine leucosis has been established as a goal in the EEC and research is revealing the ways in which this goal may be attained. To be effective, control and epidemiological monitoring must be interactive. Recently introduced serological tests, of improved sensitivity, provide a valuable tool."}
{"id": "PMID:212859", "title": "Interaction of a combined feline viral rhinotracheitis-feline calicivirus vaccine and the FVR carrier state.", "content": "The effect of field feline viral rhinotracheitis (FVR) virus challenge on cats previously vaccinated with a combined FVR/feline calicivirus intramuscular vaccine was studied in relation to the development of an FVR carrier state. There was no virus shedding of either of the two vaccine viruses following vaccination. Treatment with corticosteroid 60 days after vaccination and before challenge with FVR virus did not induce virus re-excretion in vaccinates or controls; neither did similar treatment induce shedding 63 days after challenge of both vaccinates and controls with virulent field virus. After a further 55 days however, FVR virus shedding was elicited in one of four previously vaccinated and challenged cats compared with two of four unvaccinated and challenged controls. Two sentinel cats remained virologically and serologically free of FVR throughout. The vaccine was shown to be effective in controlling the disease; 12 weeks after initial vaccination no clinical signs were seen in three of four cats following intranasal challenge with 10(5)CCID50 of virulent field FVR virus, and a mild transient unilateral ocular and nasal discharge was seen in the remaining cat for one day only. Severe clinical signs of approximately 10 days' duration were seen in all four unvaccinated challenged controls. The virological and serological responses of the cats were also recorded.", "contents": "Interaction of a combined feline viral rhinotracheitis-feline calicivirus vaccine and the FVR carrier state. The effect of field feline viral rhinotracheitis (FVR) virus challenge on cats previously vaccinated with a combined FVR/feline calicivirus intramuscular vaccine was studied in relation to the development of an FVR carrier state. There was no virus shedding of either of the two vaccine viruses following vaccination. Treatment with corticosteroid 60 days after vaccination and before challenge with FVR virus did not induce virus re-excretion in vaccinates or controls; neither did similar treatment induce shedding 63 days after challenge of both vaccinates and controls with virulent field virus. After a further 55 days however, FVR virus shedding was elicited in one of four previously vaccinated and challenged cats compared with two of four unvaccinated and challenged controls. Two sentinel cats remained virologically and serologically free of FVR throughout. The vaccine was shown to be effective in controlling the disease; 12 weeks after initial vaccination no clinical signs were seen in three of four cats following intranasal challenge with 10(5)CCID50 of virulent field FVR virus, and a mild transient unilateral ocular and nasal discharge was seen in the remaining cat for one day only. Severe clinical signs of approximately 10 days' duration were seen in all four unvaccinated challenged controls. The virological and serological responses of the cats were also recorded."}
{"id": "PMID:212862", "title": "[Serological diagnosis of bovine leukosis using the agar gel diffusion test].", "content": "Experiments were carried out to use the agar gel diffusion test (AGDT) in the study of bovine leukosis. An antigen was obtained from FLK-24 cells with a latent leukosis virus infection, which proved specific and suitable for AGDT. A total of 134 serum samples were examined applyig AGDT, for the presence of specific antibodies, originating from cattle of herds in which leukosis had been hematologically demonstrated. Investigated were also 56 sera of animals presenting an unknown clinical picture. Positive reaction was established in 70 per cent of the sera taken from herds with hematologically demonstrated leukosis. The specificity of AGDT was confirmed through establishing specific antibodies also in sera of lambs experimentally infected with a virus from a FBL-J 5 cell line with a latent infection. It is admitted that AGDT is a specific, sensitive, and readily applicable method, which can successfully be used in the diagnostics of leukosis in this country.", "contents": "[Serological diagnosis of bovine leukosis using the agar gel diffusion test]. Experiments were carried out to use the agar gel diffusion test (AGDT) in the study of bovine leukosis. An antigen was obtained from FLK-24 cells with a latent leukosis virus infection, which proved specific and suitable for AGDT. A total of 134 serum samples were examined applyig AGDT, for the presence of specific antibodies, originating from cattle of herds in which leukosis had been hematologically demonstrated. Investigated were also 56 sera of animals presenting an unknown clinical picture. Positive reaction was established in 70 per cent of the sera taken from herds with hematologically demonstrated leukosis. The specificity of AGDT was confirmed through establishing specific antibodies also in sera of lambs experimentally infected with a virus from a FBL-J 5 cell line with a latent infection. It is admitted that AGDT is a specific, sensitive, and readily applicable method, which can successfully be used in the diagnostics of leukosis in this country."}
{"id": "PMID:212864", "title": "Malignant giant cell tumor of bone. Fine structure and localization of acid phosphatase.", "content": "The fine structure of the different cell types constituting a primary malignant giant cell tumor of bone has been studied and the localization of acid phosphatase in relation to the subcellular organelles been demonstrated. Three distinct cell types with characteristic ultrastructural features were observed: giant cells, fibroblast-like cells, and cells with abundant lipid inclusions and mitochondria. Certain differences were noted between these three cell types and their counterparts in benign giant cell tumors of bone (described in a separate report). The enzyme histochemical and morphological data suggested that the giant cells in the malignant tumor might possess a more active and expansive lysosomal apparatus than corresponding cells in the benign variant.", "contents": "Malignant giant cell tumor of bone. Fine structure and localization of acid phosphatase. The fine structure of the different cell types constituting a primary malignant giant cell tumor of bone has been studied and the localization of acid phosphatase in relation to the subcellular organelles been demonstrated. Three distinct cell types with characteristic ultrastructural features were observed: giant cells, fibroblast-like cells, and cells with abundant lipid inclusions and mitochondria. Certain differences were noted between these three cell types and their counterparts in benign giant cell tumors of bone (described in a separate report). The enzyme histochemical and morphological data suggested that the giant cells in the malignant tumor might possess a more active and expansive lysosomal apparatus than corresponding cells in the benign variant."}
{"id": "PMID:212865", "title": "Electron microscopic findings in four cases of nasopharyngeal fibroma.", "content": "Light and electron microscopic investigations of four cases of juvenile nasopharyngeal fibroma revealed characteristic structures; a fibrous stroma, an inclination to hyalinisation and formation of scar like tissue, a lacunar thin walled vascular component, large numbers of mast cells and of fibroblasts. The tumor fibroblasts contained different nuclear bodies and particles. There existed five different types of more or less complex spherical bodies. The previously described nuclear electron dense particles with an electron lucent halo could be divided into four groups measuring 60, 90, 150, and 300 nm in diameter. In addition to the previously described ultrastructural properties of the tumors, the nuclei of the tumor fibroblasts were found to contain virus like particles. These particles were less electron dense, measuring 40 to 55 nm in diameter and arranged in groups throughout the nucleoplasm; they were different from chromatin condensations and from perichromatin granules. The structure and the size of the smallest particles was not comparable with the other nuclear inclusions.", "contents": "Electron microscopic findings in four cases of nasopharyngeal fibroma. Light and electron microscopic investigations of four cases of juvenile nasopharyngeal fibroma revealed characteristic structures; a fibrous stroma, an inclination to hyalinisation and formation of scar like tissue, a lacunar thin walled vascular component, large numbers of mast cells and of fibroblasts. The tumor fibroblasts contained different nuclear bodies and particles. There existed five different types of more or less complex spherical bodies. The previously described nuclear electron dense particles with an electron lucent halo could be divided into four groups measuring 60, 90, 150, and 300 nm in diameter. In addition to the previously described ultrastructural properties of the tumors, the nuclei of the tumor fibroblasts were found to contain virus like particles. These particles were less electron dense, measuring 40 to 55 nm in diameter and arranged in groups throughout the nucleoplasm; they were different from chromatin condensations and from perichromatin granules. The structure and the size of the smallest particles was not comparable with the other nuclear inclusions."}
{"id": "PMID:212872", "title": "[Isolation of the Epstein-Barr virus in suspension cell lines obtained from persons with different forms of hemoblastosis].", "content": "Isolation of EBV from patients with different types of haemoblastosis by establishing virus-producing cell lines is described. EBV was isolated from patients with myelogenous leukemia in 71%, Hodgkin's disease--in 22%. EBV was also isolated from 1 patient with lung tumor and leukemogenic reaction. All 8 established cell lines produced EBV in 0.5--3% of cells. The cells of the lines concerned are lymphoblasts and show B-cell characteristics.", "contents": "[Isolation of the Epstein-Barr virus in suspension cell lines obtained from persons with different forms of hemoblastosis]. Isolation of EBV from patients with different types of haemoblastosis by establishing virus-producing cell lines is described. EBV was isolated from patients with myelogenous leukemia in 71%, Hodgkin's disease--in 22%. EBV was also isolated from 1 patient with lung tumor and leukemogenic reaction. All 8 established cell lines produced EBV in 0.5--3% of cells. The cells of the lines concerned are lymphoblasts and show B-cell characteristics."}
{"id": "PMID:212868", "title": "[Nucleotide pool of the brains of rats during different stages of dying].", "content": "Composition of acid-extractable fraction of nucleotides was studied in brain of dying rats after acute hemorrhage. Within the first 5 min content of ATP, GTP, UTP, GDP, UDP and NAD was distinctly decreased; content of AMP, GMP, IMP, CMP, nucleosides and nitrogen bases was markedly increased. Within the following 30 min of the dying rpocess concentration of CMP and nitrogen bases was increased but content of the other substances studied was decreased as compared with the previous experimental period. Possible effect of the alterations found on reanimation of an organism is discussed.", "contents": "[Nucleotide pool of the brains of rats during different stages of dying]. Composition of acid-extractable fraction of nucleotides was studied in brain of dying rats after acute hemorrhage. Within the first 5 min content of ATP, GTP, UTP, GDP, UDP and NAD was distinctly decreased; content of AMP, GMP, IMP, CMP, nucleosides and nitrogen bases was markedly increased. Within the following 30 min of the dying rpocess concentration of CMP and nitrogen bases was increased but content of the other substances studied was decreased as compared with the previous experimental period. Possible effect of the alterations found on reanimation of an organism is discussed."}
{"id": "PMID:212873", "title": "[Viral oncogens and carcinogenesis].", "content": "The modern concepts of tumorigenic virus oncogenes are discussed. The available literature data on the identification of oncogenes of polyoma-, adeno- and oncoviruses and the corresponding protein the products of oncogenes, are reported. Under consideration is the idea of the cellular origin of virus oncogenes. It is suggested that the study of virus oncogenes would offer some new methodical approaches to the identification of cell genes, which impairment results in cell malignification.", "contents": "[Viral oncogens and carcinogenesis]. The modern concepts of tumorigenic virus oncogenes are discussed. The available literature data on the identification of oncogenes of polyoma-, adeno- and oncoviruses and the corresponding protein the products of oncogenes, are reported. Under consideration is the idea of the cellular origin of virus oncogenes. It is suggested that the study of virus oncogenes would offer some new methodical approaches to the identification of cell genes, which impairment results in cell malignification."}
{"id": "PMID:212869", "title": "[Changes in the quality of hormones in blood plasma and ischemic heart disease risk factors in 40--59-year-old men].", "content": "Testosterone, estradiol, hydrocortisone, total cholesterol, triglycerides, cholesterol of alpha-lipoproteins (alpha-CS) were estimated in blood plasma of 124 40--59 years old men examined in the course of an epidemyolodical study (representative selection). Content of insulin was estimated in 112 persons and of growth hormone--in 102 persons. Disbalance of steroid hormones (decrease in alpha-CS) was observed in men with one factor of risk of heart ischemic impairment. Occurrence of two factors of risk of heart ischemic impairment--hypertriglyceridemia and decrease in alpha-CS--was related not only to disbalance of steroid hormones but also to alteration in the ratio of protein hormones--insulin and growth hormone.", "contents": "[Changes in the quality of hormones in blood plasma and ischemic heart disease risk factors in 40--59-year-old men]. Testosterone, estradiol, hydrocortisone, total cholesterol, triglycerides, cholesterol of alpha-lipoproteins (alpha-CS) were estimated in blood plasma of 124 40--59 years old men examined in the course of an epidemyolodical study (representative selection). Content of insulin was estimated in 112 persons and of growth hormone--in 102 persons. Disbalance of steroid hormones (decrease in alpha-CS) was observed in men with one factor of risk of heart ischemic impairment. Occurrence of two factors of risk of heart ischemic impairment--hypertriglyceridemia and decrease in alpha-CS--was related not only to disbalance of steroid hormones but also to alteration in the ratio of protein hormones--insulin and growth hormone."}
{"id": "PMID:212870", "title": "[Glycosaminoglycans in the makeup of the lipid-protein complexes of the human aorta].", "content": "Lipoprotein complexes were studied in intact parts of human aorta as well as in areas of aorta impaired with atherosclerosis. The arterial walls contained particles, which were similar to pre-beta and beta-lipoproteins as evidenced by immunological properties and by size. At the same time, lipoproteins of the vascular walls differed distinctly from those of blood serum because these former lipoproteins possesed altered electrophoretic mobilities in acetyl cellulose, contained glycosamineglycans, exhibited lower rate of flotation in salt-free solution as compared with the salt-containing solution under conditions of analytical ultracentrifugation. The data obtained suggest that the lipoproteins formed complexes with glycosamineglucans in vascular walls.", "contents": "[Glycosaminoglycans in the makeup of the lipid-protein complexes of the human aorta]. Lipoprotein complexes were studied in intact parts of human aorta as well as in areas of aorta impaired with atherosclerosis. The arterial walls contained particles, which were similar to pre-beta and beta-lipoproteins as evidenced by immunological properties and by size. At the same time, lipoproteins of the vascular walls differed distinctly from those of blood serum because these former lipoproteins possesed altered electrophoretic mobilities in acetyl cellulose, contained glycosamineglycans, exhibited lower rate of flotation in salt-free solution as compared with the salt-containing solution under conditions of analytical ultracentrifugation. The data obtained suggest that the lipoproteins formed complexes with glycosamineglucans in vascular walls."}
{"id": "PMID:212883", "title": "[Diagnosis of primary hypercholesteremia--a classification of genetic factors as causes for myocardial infarct].", "content": "Cultvated lymphocytes of patients with myocardial infarction with a primary hypercholesterolaemia as well as of unconspicuous control persons take up LDL-cholesterol labelled by 125iodine. Here is evident that lymphocytes of patients with a primary hypercholesterolaemia may incorporate significantly less LDL-cholesterol than healthy control persons. Supplementing the serum lipid determinations and the lipid electrophoresis the described radiochemical investigations at the model of lymphocytes make possible a biochemically exact diagnosis of the primary hypercholesterolaemia and thus an evident genetic analysis of the patients with infarctions.", "contents": "[Diagnosis of primary hypercholesteremia--a classification of genetic factors as causes for myocardial infarct]. Cultvated lymphocytes of patients with myocardial infarction with a primary hypercholesterolaemia as well as of unconspicuous control persons take up LDL-cholesterol labelled by 125iodine. Here is evident that lymphocytes of patients with a primary hypercholesterolaemia may incorporate significantly less LDL-cholesterol than healthy control persons. Supplementing the serum lipid determinations and the lipid electrophoresis the described radiochemical investigations at the model of lymphocytes make possible a biochemically exact diagnosis of the primary hypercholesterolaemia and thus an evident genetic analysis of the patients with infarctions."}
{"id": "PMID:212884", "title": "[Intestinal hemorrhage in Klippel-Trenaunay syndrome].", "content": "It is reported on a 21-year-old patient with Klippel-Trenaunay's syndrome and simultaneous intestinal haemorrhage. Anamnesis and histological findings are discussed and the problems of therapy are explained. In the discussion the knowledge of the peripheral angiodysplasias and their differential diagnosis in literature are entered. Comparative considerations concerning the own case are made.", "contents": "[Intestinal hemorrhage in Klippel-Trenaunay syndrome]. It is reported on a 21-year-old patient with Klippel-Trenaunay's syndrome and simultaneous intestinal haemorrhage. Anamnesis and histological findings are discussed and the problems of therapy are explained. In the discussion the knowledge of the peripheral angiodysplasias and their differential diagnosis in literature are entered. Comparative considerations concerning the own case are made."}
{"id": "PMID:212885", "title": "[Electronmicroscopic findings in a malignant hepatoma after oral contraceptives (author's transl)].", "content": "In this paper we report the electronmicroscopic findings in a hepatocellular carcinoma of a 24 years old woman after taking oral contraceptives. We saw alterations of the nucleus (finger-like or finger-formed nuclei, nuclear invaginations and intranuclear vesicular membranbodies), changes of the mitochondries (number, polymorphy and osmiophil bodies) as well as changes of lysosomes (myelinshaped residualbodies). The observed and described changes are not specific for malignant tumors of the liver.", "contents": "[Electronmicroscopic findings in a malignant hepatoma after oral contraceptives (author's transl)]. In this paper we report the electronmicroscopic findings in a hepatocellular carcinoma of a 24 years old woman after taking oral contraceptives. We saw alterations of the nucleus (finger-like or finger-formed nuclei, nuclear invaginations and intranuclear vesicular membranbodies), changes of the mitochondries (number, polymorphy and osmiophil bodies) as well as changes of lysosomes (myelinshaped residualbodies). The observed and described changes are not specific for malignant tumors of the liver."}
{"id": "PMID:212886", "title": "Evaluation of continuous labelling data by a practical mathematical method with application to a virus-induced sarcoma of the rat.", "content": "A simple mathematical function is established which renders the increase of the labelling index during continuous labelling of an exponentially growing tumor. By known values of proliferative fraction, mean cell cycle time and tumor doubling time, the mode and extent of cell loss is determined. Three models for different modes of cell loss are introduced: Model A for cell loss equally affecting proliferative and resting cells; Model B for cell loss predominantly affecting one of the two cell compartments; Model C for cell loss during mitosis. The range of validity of the model function is specified. Experimental data of a Polyoma virus-induced renal sarcoma of the rat provide an example of applicability of the theoretical model.", "contents": "Evaluation of continuous labelling data by a practical mathematical method with application to a virus-induced sarcoma of the rat. A simple mathematical function is established which renders the increase of the labelling index during continuous labelling of an exponentially growing tumor. By known values of proliferative fraction, mean cell cycle time and tumor doubling time, the mode and extent of cell loss is determined. Three models for different modes of cell loss are introduced: Model A for cell loss equally affecting proliferative and resting cells; Model B for cell loss predominantly affecting one of the two cell compartments; Model C for cell loss during mitosis. The range of validity of the model function is specified. Experimental data of a Polyoma virus-induced renal sarcoma of the rat provide an example of applicability of the theoretical model."}
{"id": "PMID:212888", "title": "Multiple functions of thioredoxins.", "content": "Reduced thioredoxins from microbial and plant cells, both of cytoplasmic or chloroplast origin, are interchangeable in stimulating such diverse enzyme activities as ribonucleoside diphosphate reductase (E. coli), PAPS sulfotransferase (Synechococcus), and fructose-1,6-bis-phosphatase (from spinach) in vitro. It is suggested that reduced thioredoxins are unspecific, multifunctional cellular proteins while in contrast the oxidized froms require specific enzymes for their reduction.", "contents": "Multiple functions of thioredoxins. Reduced thioredoxins from microbial and plant cells, both of cytoplasmic or chloroplast origin, are interchangeable in stimulating such diverse enzyme activities as ribonucleoside diphosphate reductase (E. coli), PAPS sulfotransferase (Synechococcus), and fructose-1,6-bis-phosphatase (from spinach) in vitro. It is suggested that reduced thioredoxins are unspecific, multifunctional cellular proteins while in contrast the oxidized froms require specific enzymes for their reduction."}
{"id": "PMID:212889", "title": "Isolation of single stranded DNA from purified hepatitis A-virus.", "content": "Hepatitis A-virus was purified from human stools by three purification steps. Virus was identified by radioimmunoassay and purity monitored with immune electron microscopy. Virus particles, serologically and morphologically identical, banded in CsCl in two density ranges at 1.31-1.34 g/cm3 and at 1.41-1.43 g/cm3. Virions of density 1.31-1.34 g/cm3 were shown to contain single-stranded DNA of different size classes. Class I 1.33 kb, class II 4.61 kb in addition a small amount of molecules was detected with lengths up to 15 kb.", "contents": "Isolation of single stranded DNA from purified hepatitis A-virus. Hepatitis A-virus was purified from human stools by three purification steps. Virus was identified by radioimmunoassay and purity monitored with immune electron microscopy. Virus particles, serologically and morphologically identical, banded in CsCl in two density ranges at 1.31-1.34 g/cm3 and at 1.41-1.43 g/cm3. Virions of density 1.31-1.34 g/cm3 were shown to contain single-stranded DNA of different size classes. Class I 1.33 kb, class II 4.61 kb in addition a small amount of molecules was detected with lengths up to 15 kb."}
{"id": "PMID:212901", "title": "[Vaccination and morbidity in Basel school-children (measles, mumps, rubella, chickenpox, cytomegalic inclusion disease)].", "content": "Antibodies against diseases of childhood have been determined in fall 1977 taking bloodsamples of 430 15-year old students. Immunity was widespread for measles (96%), chickenpox (93%), mumps (90%) whereas 27% did not have antibodies against rubella. The level of vaccination (measles, mumps, rubella) is increasing fast in younger children. The possibility of being infected by a wild virus will be low in the future for those who have not been vaccinated. Antibodies against Cytomegalovirus were measured in 120 students of normalschool and 107 \"gymnasiasts\". The proportion between negative and positive was 1.1 for students in normalschool and 2.7 for those attending a higher education.", "contents": "[Vaccination and morbidity in Basel school-children (measles, mumps, rubella, chickenpox, cytomegalic inclusion disease)]. Antibodies against diseases of childhood have been determined in fall 1977 taking bloodsamples of 430 15-year old students. Immunity was widespread for measles (96%), chickenpox (93%), mumps (90%) whereas 27% did not have antibodies against rubella. The level of vaccination (measles, mumps, rubella) is increasing fast in younger children. The possibility of being infected by a wild virus will be low in the future for those who have not been vaccinated. Antibodies against Cytomegalovirus were measured in 120 students of normalschool and 107 \"gymnasiasts\". The proportion between negative and positive was 1.1 for students in normalschool and 2.7 for those attending a higher education."}
{"id": "PMID:212902", "title": "[Serum lipoproteins in family members of myocardial infarct victims].", "content": "Men 40 to 59 years old, first degree relatives of patients with myocardial infarction had a lower HDL-cholesterol concentration than a control group. This is in analogy with the low concentration of HDL-cholesterol observed in the myocardial infarction patients themselves. LDL and VLDL in relatives were not elevated in comparison to the controls. The low HDL-cholesterol could be the expression of a familial defect in cholesterol transport.", "contents": "[Serum lipoproteins in family members of myocardial infarct victims]. Men 40 to 59 years old, first degree relatives of patients with myocardial infarction had a lower HDL-cholesterol concentration than a control group. This is in analogy with the low concentration of HDL-cholesterol observed in the myocardial infarction patients themselves. LDL and VLDL in relatives were not elevated in comparison to the controls. The low HDL-cholesterol could be the expression of a familial defect in cholesterol transport."}
{"id": "PMID:212907", "title": "[Effect of alloxan diabetes on (Na+ + K+)-activated ATPase in brush border membrane of the mucosal cell of rat small intestine].", "content": "In order to elucidate a possible relationship between (Na+ + K+)-activated ATPase and intestinal absorption of actively transported monosaccharides enzyme activity was measured in mucosal cells from alloxan diabetic rats. The general effect of increasing capacity of active, Na+-dependent transport processes in diabetes mellitus is associated with a significantly enhanced (Na+ +K+)-activated ATPase activity in mucosal homogenate from diabetic animals. To study the localization of these effects within the cell we isolated purified brush borders and their substructures. To enable a comparison to be made between preparation procedures of diabetic and control animals the fractions were controlled by electronmicroscopy and by measuring the sucrase activity. In the purified brush border fraction of alloxan treated rats there was no significant increase in (Na+ + K+)-activated ATPase activity. Based on these results we conclude that the (Na+ + K+)-activated ATPase in the basolateral membranes was increased in alloxan diabetes, and it seems very likely that this enzyme is involved in the regulation of Na+-dependent transport processes.", "contents": "[Effect of alloxan diabetes on (Na+ + K+)-activated ATPase in brush border membrane of the mucosal cell of rat small intestine]. In order to elucidate a possible relationship between (Na+ + K+)-activated ATPase and intestinal absorption of actively transported monosaccharides enzyme activity was measured in mucosal cells from alloxan diabetic rats. The general effect of increasing capacity of active, Na+-dependent transport processes in diabetes mellitus is associated with a significantly enhanced (Na+ +K+)-activated ATPase activity in mucosal homogenate from diabetic animals. To study the localization of these effects within the cell we isolated purified brush borders and their substructures. To enable a comparison to be made between preparation procedures of diabetic and control animals the fractions were controlled by electronmicroscopy and by measuring the sucrase activity. In the purified brush border fraction of alloxan treated rats there was no significant increase in (Na+ + K+)-activated ATPase activity. Based on these results we conclude that the (Na+ + K+)-activated ATPase in the basolateral membranes was increased in alloxan diabetes, and it seems very likely that this enzyme is involved in the regulation of Na+-dependent transport processes."}
{"id": "PMID:212908", "title": "Analysis of function-related interactions of ATP, sodium and potassium ions with Na+- and K+-transporting ATPase studied with a thiol reagent as tool.", "content": "The paper describes the interaction of ATP, Na+ and K+ with (NaK)-ATPase exploiting the inactivation by reaction with NBD-chloride as an analytical tool for the evaluation of enzyme ligandation with the various effectors. 1. The inactivation of (NaK)-ATPase by reaction with NBD-chloride showing under all conditions studied a pseudo first-order rate rests on the alkylation of thiol groups in or near catalytic centre. ATP bound to catalytic centre prevents from enzyme inactivation by NDD-chloride through protection of these thiol groups from alkylation. Na+ and K+ affect the reactivity of the thiol groups towards NBD-chloride either indirectly via influencing ATP binding or more directly via changing the conformation of catalytic centre. Proceeding from these interrelations, the interaction of the various effectors with the enzyme was analyzed. 2. The K'D-values of various nucleotides determined by our approach correspond to the values obtained by independent methods. As shown for the first time, two catalytic centres per enzyme molecule exist. They exhibit high or low affinity to both ATP and ADP apparently caused by anticooperative interaction of the half-units of the enzyme through intersubunit communication (\"half-of-the-sites reactivity\"). 3. In the absence of ATP, Na+ or K+ ligandation of (NaK)-ATPase produce opposite effects on the reactivity of the thiol groups of catalytic centres reflecting different changes of their conformation. This corresponds to the well-known antagonistic effect of Na+ and K+ on some partial reactions of (NaK)-ATPase. The Na+ and K+ concentrations required to change thiol reactivity are rather high, i.e. the ionophoric centres for both Na+ and K+ are not readily accessible for cation complexation in the absence of enzyme complexation with ATP. 4. Na+ being without effect on ATP binding to the enzyme also does not influence the inactivating reaction with NBD-chloride while K+ by decreasing ATP binding dramatically decreases the protective effect of ATP. The K+ affinity of the enzyme-ATP complex is by more than two orders of magnitude higher than that of free enzyme. Na+ ligandation of the K+-liganded enzyme-ATP complex reverses the effect of K+ ligandation and produces a protective effect which distinctly surpasses that of the complexation of free enzyme with ATP. Hence, the enzyme molecule carries simultaneously ionophoric centres for both Na+ and K+. 5. The findings that per enzyme molecule ionophoric centres for Na+ and K+, and two catalytic centres with anticooperative interaction coexist corroborate the corresponding basic predictions of the flip-flop concept of (NaK)-ATPase pump mechanism, and explain some peculiar kinetic features of transport and enzyme activities of (NaK)-ATPase.", "contents": "Analysis of function-related interactions of ATP, sodium and potassium ions with Na+- and K+-transporting ATPase studied with a thiol reagent as tool. The paper describes the interaction of ATP, Na+ and K+ with (NaK)-ATPase exploiting the inactivation by reaction with NBD-chloride as an analytical tool for the evaluation of enzyme ligandation with the various effectors. 1. The inactivation of (NaK)-ATPase by reaction with NBD-chloride showing under all conditions studied a pseudo first-order rate rests on the alkylation of thiol groups in or near catalytic centre. ATP bound to catalytic centre prevents from enzyme inactivation by NDD-chloride through protection of these thiol groups from alkylation. Na+ and K+ affect the reactivity of the thiol groups towards NBD-chloride either indirectly via influencing ATP binding or more directly via changing the conformation of catalytic centre. Proceeding from these interrelations, the interaction of the various effectors with the enzyme was analyzed. 2. The K'D-values of various nucleotides determined by our approach correspond to the values obtained by independent methods. As shown for the first time, two catalytic centres per enzyme molecule exist. They exhibit high or low affinity to both ATP and ADP apparently caused by anticooperative interaction of the half-units of the enzyme through intersubunit communication (\"half-of-the-sites reactivity\"). 3. In the absence of ATP, Na+ or K+ ligandation of (NaK)-ATPase produce opposite effects on the reactivity of the thiol groups of catalytic centres reflecting different changes of their conformation. This corresponds to the well-known antagonistic effect of Na+ and K+ on some partial reactions of (NaK)-ATPase. The Na+ and K+ concentrations required to change thiol reactivity are rather high, i.e. the ionophoric centres for both Na+ and K+ are not readily accessible for cation complexation in the absence of enzyme complexation with ATP. 4. Na+ being without effect on ATP binding to the enzyme also does not influence the inactivating reaction with NBD-chloride while K+ by decreasing ATP binding dramatically decreases the protective effect of ATP. The K+ affinity of the enzyme-ATP complex is by more than two orders of magnitude higher than that of free enzyme. Na+ ligandation of the K+-liganded enzyme-ATP complex reverses the effect of K+ ligandation and produces a protective effect which distinctly surpasses that of the complexation of free enzyme with ATP. Hence, the enzyme molecule carries simultaneously ionophoric centres for both Na+ and K+. 5. The findings that per enzyme molecule ionophoric centres for Na+ and K+, and two catalytic centres with anticooperative interaction coexist corroborate the corresponding basic predictions of the flip-flop concept of (NaK)-ATPase pump mechanism, and explain some peculiar kinetic features of transport and enzyme activities of (NaK)-ATPase."}
{"id": "PMID:212909", "title": "[Separation of enriched synaptosomes, synaptic vesicles and synaptic plasma membranes].", "content": "A rapid and simple method is described for separation of intact synaptosomes, synaptic plasma membranes and vesicles. Two synaptosome fractions were obtained by modified differential centrifugation. The rate zonal zentrifugation in a linear sucrose gradient (very low density) is suitable to obtain fractions highly enriched in synaptic plasma membranes and vesicles. Examination of the prepared fractions was done by enzyme marker activities and electron microscopy", "contents": "[Separation of enriched synaptosomes, synaptic vesicles and synaptic plasma membranes]. A rapid and simple method is described for separation of intact synaptosomes, synaptic plasma membranes and vesicles. Two synaptosome fractions were obtained by modified differential centrifugation. The rate zonal zentrifugation in a linear sucrose gradient (very low density) is suitable to obtain fractions highly enriched in synaptic plasma membranes and vesicles. Examination of the prepared fractions was done by enzyme marker activities and electron microscopy"}
{"id": "PMID:212910", "title": "[Concentration and composition of serum lipoproteins in the fetal rat].", "content": "1. Concentration and composition of the \"very low density lipoproteins\" (VLDL), \"low density lipoproteins\" (LDL) and \"high density lipoproteins\" (HDL) and of non-floatable lipids of fetal rat serum (day 22 of pregnancy) were determined by ultracentrifugation, thin-layer chromatographic separation of the floated lipids and quantitation of the lipid and protein moiety. 2. The concentration of VLDL is in the fetal rat by one order of magnitude lower, and that of LDL, 5fold higher than in the adult animal; the concentration of HDL in fetal serum amounts to 60% of the value of adult animals. 3. The composition of LDL and HDL of fetal serum does not differ from that in the serum of adult animals; in contrast, the fetal VLDL have a higher proportion of protein and cholesterol and a lower proportion of triglycerides than the VLDL of adult serum. The electrophoretic mobility of the fetal VLDL is lower than that of adult VLDL.", "contents": "[Concentration and composition of serum lipoproteins in the fetal rat]. 1. Concentration and composition of the \"very low density lipoproteins\" (VLDL), \"low density lipoproteins\" (LDL) and \"high density lipoproteins\" (HDL) and of non-floatable lipids of fetal rat serum (day 22 of pregnancy) were determined by ultracentrifugation, thin-layer chromatographic separation of the floated lipids and quantitation of the lipid and protein moiety. 2. The concentration of VLDL is in the fetal rat by one order of magnitude lower, and that of LDL, 5fold higher than in the adult animal; the concentration of HDL in fetal serum amounts to 60% of the value of adult animals. 3. The composition of LDL and HDL of fetal serum does not differ from that in the serum of adult animals; in contrast, the fetal VLDL have a higher proportion of protein and cholesterol and a lower proportion of triglycerides than the VLDL of adult serum. The electrophoretic mobility of the fetal VLDL is lower than that of adult VLDL."}
{"id": "PMID:212911", "title": "[Development of serum lipoproteins from fetal to adult rats].", "content": "1. The semi-quantitative development of lipoproteins in the serum (beta-, pre-beta- and alpha-lipoproteins) from fetal (day 18 of intra-uterine development) to adult age was determined by agarose gel electrophoresis and determination of total lipids. 2. A high proportion of beta- and a very low proportion of pre-beta-lipoprotein is typical of the fetal stage. In adult age, however, the beta-lipoproteins are the smallest fraction, and the pre-beta-lipoproteins, the second-strongest fraction. 3. The transition from fetal to adult lipoprotein pattern is more or less abrupt, with the change of the proportion for each of the three lipoprotein fractions occurring at different intervals from birth. Adaptation of the fetal lipoprotein status to that of the adult animal in regard to quantity and mutual relationship of the fractions was observable, at the earliest, 7 weeks after birth.", "contents": "[Development of serum lipoproteins from fetal to adult rats]. 1. The semi-quantitative development of lipoproteins in the serum (beta-, pre-beta- and alpha-lipoproteins) from fetal (day 18 of intra-uterine development) to adult age was determined by agarose gel electrophoresis and determination of total lipids. 2. A high proportion of beta- and a very low proportion of pre-beta-lipoprotein is typical of the fetal stage. In adult age, however, the beta-lipoproteins are the smallest fraction, and the pre-beta-lipoproteins, the second-strongest fraction. 3. The transition from fetal to adult lipoprotein pattern is more or less abrupt, with the change of the proportion for each of the three lipoprotein fractions occurring at different intervals from birth. Adaptation of the fetal lipoprotein status to that of the adult animal in regard to quantity and mutual relationship of the fractions was observable, at the earliest, 7 weeks after birth."}
{"id": "PMID:212913", "title": "[Paget's cancer of male breast].", "content": "The case of a male patient with Paget's cancer of the breast is reported. Radical mastectomy was performed. Two and a half years later the patient was free of symptoms.", "contents": "[Paget's cancer of male breast]. The case of a male patient with Paget's cancer of the breast is reported. Radical mastectomy was performed. Two and a half years later the patient was free of symptoms."}
{"id": "PMID:212914", "title": "Some urgent problems in the treatment of operable breast cancer.", "content": "The results of 1216 radical mastectomies and 297 conservative surgical interventions performed on 1513 operable mammary carcinoma patients between 1950 and 1962 are analysed on the basis of the 10 years survival rate. It appears that early diagnosis and early operation will give the best result. The bioloical activity of the tumour is the most decisive additional factor.", "contents": "Some urgent problems in the treatment of operable breast cancer. The results of 1216 radical mastectomies and 297 conservative surgical interventions performed on 1513 operable mammary carcinoma patients between 1950 and 1962 are analysed on the basis of the 10 years survival rate. It appears that early diagnosis and early operation will give the best result. The bioloical activity of the tumour is the most decisive additional factor."}
{"id": "PMID:212917", "title": "ACTH and cortisol response to bromocriptine, and results of long-term therapy, in Cushing's disease.", "content": "Plasma corticotrophin (ACTH) was lowered in 4 out of 5 patients with pituitary dependent Cushing's syndrome (one of whom was studied only after bilateral adrenalectomy) after a single oral dose of 2.5 mg bromocriptine, but plasma cortisols were unaltered in the 3 patients in whom it was measured. Three patients were observed during treatment with bromocriptine for 16 to 87 weeks. One improved symptomatically while maintained on a combination of metyrapone and bromocriptine, but plasma ACTH levels remained high even when the dose of bromocriptine was increased to 20 mg daily. Bromocriptine therapy was discontinued after 16 weeks in the second patient due to the development of mental depression. Her clinical features had not improved during this time. The third patient, who also underwent a course of pituitary irradiation, became, and remains, symptom free, with satisfactory plasma ACTH and cortisol levels for the 87 weeks he has received bromocriptine. The role of bromocriptine in the management of Cushing's disease seems limited despite the fact that plasma ACTH may fall after a test dose of the drug.", "contents": "ACTH and cortisol response to bromocriptine, and results of long-term therapy, in Cushing's disease. Plasma corticotrophin (ACTH) was lowered in 4 out of 5 patients with pituitary dependent Cushing's syndrome (one of whom was studied only after bilateral adrenalectomy) after a single oral dose of 2.5 mg bromocriptine, but plasma cortisols were unaltered in the 3 patients in whom it was measured. Three patients were observed during treatment with bromocriptine for 16 to 87 weeks. One improved symptomatically while maintained on a combination of metyrapone and bromocriptine, but plasma ACTH levels remained high even when the dose of bromocriptine was increased to 20 mg daily. Bromocriptine therapy was discontinued after 16 weeks in the second patient due to the development of mental depression. Her clinical features had not improved during this time. The third patient, who also underwent a course of pituitary irradiation, became, and remains, symptom free, with satisfactory plasma ACTH and cortisol levels for the 87 weeks he has received bromocriptine. The role of bromocriptine in the management of Cushing's disease seems limited despite the fact that plasma ACTH may fall after a test dose of the drug."}
{"id": "PMID:212915", "title": "Coxsackie B4 viral infection, anti-islet immunity and immunogenetics in insulin-dependent diabetes mellitus.", "content": "The interrelationship between Coxsackie B4 (CB4) virus antibodies, islet-cell antibodies and HLA B8 was studied in 67 patients with juvenile-onset diabetes mellitus (JOD). In 41 JOD patients (61%) CB4 antibodies (greater than 1:4) were found. A high prevalence (69%) of significant CB4 antibody titers (greater than 1:64) was observed in patients with age at onset between 11 and 20 years compared with those with age at onset below or over that age-range (27% and 33%, respectively). Islet-cell antibodies (ICA) could be detected only in 11 JOD patients, which is probably due to the relatively long mean duration of disease. However, 8 of them presented with significant CB4 antibody production. Although no correlation between CB4 antibodies and the JOD-associated HLA-antigens (B8, Bw15, Cw3 and B7) could be detected in the entire group of JOD patients, a close association between ICA persistence and HLA B8 was found. Furthermore, in the ICA-positive, moderate or high CB4 antibody titers were prevalent. Thus, the present data point to a possible interrelationship between CB4 virus antibodies, persistent ICA production and HLA B8 in a minor proportion of JOD patients. However, it seems premature to assume direct implication of these factors in the pathogenesis of JOD.", "contents": "Coxsackie B4 viral infection, anti-islet immunity and immunogenetics in insulin-dependent diabetes mellitus. The interrelationship between Coxsackie B4 (CB4) virus antibodies, islet-cell antibodies and HLA B8 was studied in 67 patients with juvenile-onset diabetes mellitus (JOD). In 41 JOD patients (61%) CB4 antibodies (greater than 1:4) were found. A high prevalence (69%) of significant CB4 antibody titers (greater than 1:64) was observed in patients with age at onset between 11 and 20 years compared with those with age at onset below or over that age-range (27% and 33%, respectively). Islet-cell antibodies (ICA) could be detected only in 11 JOD patients, which is probably due to the relatively long mean duration of disease. However, 8 of them presented with significant CB4 antibody production. Although no correlation between CB4 antibodies and the JOD-associated HLA-antigens (B8, Bw15, Cw3 and B7) could be detected in the entire group of JOD patients, a close association between ICA persistence and HLA B8 was found. Furthermore, in the ICA-positive, moderate or high CB4 antibody titers were prevalent. Thus, the present data point to a possible interrelationship between CB4 virus antibodies, persistent ICA production and HLA B8 in a minor proportion of JOD patients. However, it seems premature to assume direct implication of these factors in the pathogenesis of JOD."}
{"id": "PMID:212916", "title": "Insulinoma with hypoglycemia and normal immunoreactive insulin but with an insulin-like activity restricted to the portal vein.", "content": "In a 46-year old Caucasian woman, the authors report a B-cell adenoma with plasma immunoreactive insulin (IRI) ranging from 10 to 32 microunits/ml, despite severe spontaneous hypoglycemia. In a peroperative sample withdrawn from the portal vein, normal IRI (40 micromicron/ml) in the presence of high insulin-like activity (290 microunits/ml) was observed by using a biological assay performed on rat epididymal fat tissue. Furthermore, this material did not cross-react with insulin antibodies and was undetectable in systemic venous samples. Although further identification by chromatographic extraction was not performed, the substance secreted by the tumor is probably identical to the non-suppressible insulin-like activity (NSILA) isolated by Froesch and responsible for hypoglycemia in a few cases of extrapancreatic tumors. The absence of this material in systemic samples indicates an immediate removal by a single passage through the liver.", "contents": "Insulinoma with hypoglycemia and normal immunoreactive insulin but with an insulin-like activity restricted to the portal vein. In a 46-year old Caucasian woman, the authors report a B-cell adenoma with plasma immunoreactive insulin (IRI) ranging from 10 to 32 microunits/ml, despite severe spontaneous hypoglycemia. In a peroperative sample withdrawn from the portal vein, normal IRI (40 micromicron/ml) in the presence of high insulin-like activity (290 microunits/ml) was observed by using a biological assay performed on rat epididymal fat tissue. Furthermore, this material did not cross-react with insulin antibodies and was undetectable in systemic venous samples. Although further identification by chromatographic extraction was not performed, the substance secreted by the tumor is probably identical to the non-suppressible insulin-like activity (NSILA) isolated by Froesch and responsible for hypoglycemia in a few cases of extrapancreatic tumors. The absence of this material in systemic samples indicates an immediate removal by a single passage through the liver."}
{"id": "PMID:212923", "title": "Corona virus induced subacute demyelinating encephalomyelitis in rats: a morphological analysis.", "content": "Thirty percent of weanling rats infected with JHM murine corona virus developed a subacute demyelinating encephalomyelitis approximately 3 weeks after intracerebral inoculation. Small demyelinating foci were located in the deep cerebral white matter and large, sharply demarcated demyelinating lesions were detectabll preserved in the demyelinating plaques in areas where the lesions extended to the gray matter. Perivascular cuffings, consisting of plasma cells and mononuclear cells, were frequently found. Viral antigen was found mostly in the white matter and in glial cells, leaving neurons unstained. Electron microscopic studies of the early lesions of white matter disclosed two different kinds of cell degeneration which developed prior to the myelin disruption and mononuclear cell infiltration. One was a small pyknotic cell, which is thought to be an oligodendrocyte and the other is a ballooned cell containing abundant microtubules. Virus particles could be demonstrated only in the latter cell type. Discussion about astrocytes as well as oligodendrocytes was made in relation to the initial stage of demyelination caused by virus infection. This animal model may be useful in the analysis of the mechanisms leading to demyelination in subacute or chronic infections.", "contents": "Corona virus induced subacute demyelinating encephalomyelitis in rats: a morphological analysis. Thirty percent of weanling rats infected with JHM murine corona virus developed a subacute demyelinating encephalomyelitis approximately 3 weeks after intracerebral inoculation. Small demyelinating foci were located in the deep cerebral white matter and large, sharply demarcated demyelinating lesions were detectabll preserved in the demyelinating plaques in areas where the lesions extended to the gray matter. Perivascular cuffings, consisting of plasma cells and mononuclear cells, were frequently found. Viral antigen was found mostly in the white matter and in glial cells, leaving neurons unstained. Electron microscopic studies of the early lesions of white matter disclosed two different kinds of cell degeneration which developed prior to the myelin disruption and mononuclear cell infiltration. One was a small pyknotic cell, which is thought to be an oligodendrocyte and the other is a ballooned cell containing abundant microtubules. Virus particles could be demonstrated only in the latter cell type. Discussion about astrocytes as well as oligodendrocytes was made in relation to the initial stage of demyelination caused by virus infection. This animal model may be useful in the analysis of the mechanisms leading to demyelination in subacute or chronic infections."}
{"id": "PMID:212924", "title": "[The neuropathies of monoclonal gammapathies. Immunofluorescence and immunolabelling in the electron microscopy of immunoglobulins with amyloid structure (author's transl)].", "content": "Five cases of peripheral neuropathies occurring with monoclonal gammapathies are studied by means of nerve biopsies. Immunofluorescence and HRP-immunolabelling with the electron microscope are performed. The direct pathogenic role of a subperineurial immunoglobulin deposit is pointed out. The relationship of the heavy chain monoclonal immunoglobulin with amyloid fibrils is discussed.", "contents": "[The neuropathies of monoclonal gammapathies. Immunofluorescence and immunolabelling in the electron microscopy of immunoglobulins with amyloid structure (author's transl)]. Five cases of peripheral neuropathies occurring with monoclonal gammapathies are studied by means of nerve biopsies. Immunofluorescence and HRP-immunolabelling with the electron microscope are performed. The direct pathogenic role of a subperineurial immunoglobulin deposit is pointed out. The relationship of the heavy chain monoclonal immunoglobulin with amyloid fibrils is discussed."}
{"id": "PMID:212925", "title": "Herpes simplex virus replication in pheochromocytoma cell line that responds to nerve growth factor.", "content": "Cultured cells of neural origin (PC-12, pheochromocytoma cell line) respond to nerve growth factor (NGF) by extending neurites. These cells whether treated with NGF or not can be infected with herpes simplex virus and produce progeny virus. Viral antigens are detected on the cell surface and fusion of cells to form polykaryocytes takes place. Nucleocapsids are found within the cell nucleus and enveloped virus in a present both in the cytoplasm and extracellular space. Virus was not observed within the neurites but laterations in the neurite microtubular structure occurred after infection.", "contents": "Herpes simplex virus replication in pheochromocytoma cell line that responds to nerve growth factor. Cultured cells of neural origin (PC-12, pheochromocytoma cell line) respond to nerve growth factor (NGF) by extending neurites. These cells whether treated with NGF or not can be infected with herpes simplex virus and produce progeny virus. Viral antigens are detected on the cell surface and fusion of cells to form polykaryocytes takes place. Nucleocapsids are found within the cell nucleus and enveloped virus in a present both in the cytoplasm and extracellular space. Virus was not observed within the neurites but laterations in the neurite microtubular structure occurred after infection."}
{"id": "PMID:212930", "title": "Passive transfer of virus induced diabetes mellitus with spleen cells.", "content": "The study describes passive transfer of diabetes mellitus by transplantation of spleen cells from donor mice infected with a diabetogenic encephalomyocarditis virus. Inbred normal C57 mice were used as both donors and recipients, and other recipients were C57 athymic, nude mice. Transplants were made in two series after 12 and 22 days duration of infection of the donors, respectively. All recipients became diabetic. The possibility of virus transfer with the spleen cell transplant is discussed, and found to be highly improbable. The fact that passive cellular transfer can be effected points to a decisive significance of the thymus dependent lymphocyte system in the pathogenesis of the primary diabetes.", "contents": "Passive transfer of virus induced diabetes mellitus with spleen cells. The study describes passive transfer of diabetes mellitus by transplantation of spleen cells from donor mice infected with a diabetogenic encephalomyocarditis virus. Inbred normal C57 mice were used as both donors and recipients, and other recipients were C57 athymic, nude mice. Transplants were made in two series after 12 and 22 days duration of infection of the donors, respectively. All recipients became diabetic. The possibility of virus transfer with the spleen cell transplant is discussed, and found to be highly improbable. The fact that passive cellular transfer can be effected points to a decisive significance of the thymus dependent lymphocyte system in the pathogenesis of the primary diabetes."}
{"id": "PMID:212926", "title": "Pulse volume recordings in outer ear canal in pulse synchronous tinnitus. A comparison between ears with Glomus tumour, serous otitis media, and normal ears.", "content": "With the aid of a volume flowmeter it is possible to record pulse synchromous volumetric changes in the outer ear canal. In 7 ears with glomus tumour in the tympanic cavity and in 5 with serous otitis media, such changes were larger than in 125 persons with a normal middle ear. By changing the ambient pressure in a pressure chamber and instructing the patients not to swallow, the drum can be pushed inward or outward. In all the cases of glomus tumour studied the pulse volumetric change was considerably affected when the drum was pushed inward or outward. In the normal patients the change was no change at all. This means that the pulse volume changes in normals are generated mainly by the vessels in the outer ear canal.", "contents": "Pulse volume recordings in outer ear canal in pulse synchronous tinnitus. A comparison between ears with Glomus tumour, serous otitis media, and normal ears. With the aid of a volume flowmeter it is possible to record pulse synchromous volumetric changes in the outer ear canal. In 7 ears with glomus tumour in the tympanic cavity and in 5 with serous otitis media, such changes were larger than in 125 persons with a normal middle ear. By changing the ambient pressure in a pressure chamber and instructing the patients not to swallow, the drum can be pushed inward or outward. In all the cases of glomus tumour studied the pulse volumetric change was considerably affected when the drum was pushed inward or outward. In the normal patients the change was no change at all. This means that the pulse volume changes in normals are generated mainly by the vessels in the outer ear canal."}
{"id": "PMID:212927", "title": "Labyrinthine and somatosensory convergence upon vestibulospinal neurons.", "content": "In awake cats cells forming the lateral (LVST) and medial (MVST) vestibulospinal tracts were identified by employing antidromic stimulation of the spinal cord. Neuronal responses to bilateral vestibular, forelimb, hindlimb, and neck electrical nerve stimulation were analysed. Extracellular recording in the vestibular nuclei was performed via a glass micropipette saturated with Fast Green, to aid in later histological tract identification. The number of cells projecting to cervical and lumbar regions in the dorsal and ventral division of Deiters' nucleus did not differ significantly. An unexpectedly large number of MVST units was found in the descending nucleus. Some MVST units projected to the lumbar cord but in both the medial and descending nuclei, projections to the cervical cord were in majority. Almost all spinal projecting vestibular neurons received labyrinthine input and more than half received somatosensory input. The units could be separated into several populations on basis of excitatory and inhibitory labyrinthine response latencies indicating multiple pathways. As regards labyrinthine-somatosensory integration the two tracts were found to be quite similar. The extent and complexity of labyrinthine-somatosensory convergence indicate the importance of feed-back mechanisms upon postural controls also at the level of the vestibular nuclei.", "contents": "Labyrinthine and somatosensory convergence upon vestibulospinal neurons. In awake cats cells forming the lateral (LVST) and medial (MVST) vestibulospinal tracts were identified by employing antidromic stimulation of the spinal cord. Neuronal responses to bilateral vestibular, forelimb, hindlimb, and neck electrical nerve stimulation were analysed. Extracellular recording in the vestibular nuclei was performed via a glass micropipette saturated with Fast Green, to aid in later histological tract identification. The number of cells projecting to cervical and lumbar regions in the dorsal and ventral division of Deiters' nucleus did not differ significantly. An unexpectedly large number of MVST units was found in the descending nucleus. Some MVST units projected to the lumbar cord but in both the medial and descending nuclei, projections to the cervical cord were in majority. Almost all spinal projecting vestibular neurons received labyrinthine input and more than half received somatosensory input. The units could be separated into several populations on basis of excitatory and inhibitory labyrinthine response latencies indicating multiple pathways. As regards labyrinthine-somatosensory integration the two tracts were found to be quite similar. The extent and complexity of labyrinthine-somatosensory convergence indicate the importance of feed-back mechanisms upon postural controls also at the level of the vestibular nuclei."}
{"id": "PMID:212928", "title": "Viral culture and electron microscopy of ganglion cells in Meniere's disease and Bell's palsy.", "content": "Specimens of Scarpa's ganglion during vestibular neurectomy were obtained in 6 cases of Meniere's disease and specimens of geniculate ganglion in 2 cases of total facial nerve decompression and studied by tissue culture methods for detection of possible herpes and cytomegalovirus infection. In electron microscopy inclusions in the form of interwoven yarn-like structures, coarse aggregates of chromatin and light nuclear bodies were found in several vestibular ganglion cells. No typical herpes virus virions could be demonstrated. The culture for viruses all proved finally negative. At present there is no proof that viruses are present in Scarpa's or geniculate ganglions but the possibility remains that the inclusion bodies observed might be viruses inactivated inside the ganglion cells.", "contents": "Viral culture and electron microscopy of ganglion cells in Meniere's disease and Bell's palsy. Specimens of Scarpa's ganglion during vestibular neurectomy were obtained in 6 cases of Meniere's disease and specimens of geniculate ganglion in 2 cases of total facial nerve decompression and studied by tissue culture methods for detection of possible herpes and cytomegalovirus infection. In electron microscopy inclusions in the form of interwoven yarn-like structures, coarse aggregates of chromatin and light nuclear bodies were found in several vestibular ganglion cells. No typical herpes virus virions could be demonstrated. The culture for viruses all proved finally negative. At present there is no proof that viruses are present in Scarpa's or geniculate ganglions but the possibility remains that the inclusion bodies observed might be viruses inactivated inside the ganglion cells."}
{"id": "PMID:212932", "title": "Immunocytochemical evidence of SV 40-related T antigen in two human brain tumours of ependymal origin.", "content": "A series of thirty-time human brain tumours has been screened for the presence or absence of SV 40-related T antigen by the direct and indirect immunoperoxidase techniques. Two tumours (an ependymoma and a choroid plexus papilloma) of ependymal origin revealed markedly positive nuclear staining for T antigen both in in vivo and in vitro. The possible viral etiology of these human brain tumours is discussed in relation to recent human papovavirus isolates.", "contents": "Immunocytochemical evidence of SV 40-related T antigen in two human brain tumours of ependymal origin. A series of thirty-time human brain tumours has been screened for the presence or absence of SV 40-related T antigen by the direct and indirect immunoperoxidase techniques. Two tumours (an ependymoma and a choroid plexus papilloma) of ependymal origin revealed markedly positive nuclear staining for T antigen both in in vivo and in vitro. The possible viral etiology of these human brain tumours is discussed in relation to recent human papovavirus isolates."}
{"id": "PMID:212931", "title": "Inhibition of evoked tongue jerks during the rat's cerebral ventricles perfusion with gamma-aminobutiric acid and beta-phenyl-gamma-aminobutiric acid.", "content": "The supraorbital branch of the trigeminal nerve of rats in chloralose anaesthesia was stimulated with electrical pulses. The stimulation of the afferent fibres of the trigeminal nerve evoked the retractive jerks of the outstretched tongue. These evoked tongue jerks (ETJ) were recorded on the tape of the line recorder through an isotonic transducer. The caniulae were inserted into the lateral cerebral ventricles by means of streotaxic apparatus and perfusion was performed with inflow of GABA or beta-phenyl-GABA-containing fluid into the right lateral ventricle and outflow through the left lateral ventricle. Perfusion with solution of 0.01 mol/l GABA reduced the amplitude of ETJ 25.9% while perfusion with hypertonic NaCl solution increased it by 19.5%, and perfusion with solution of 0.2 mol/l beta-phenyl-GABA reduced that amplitude by 39.9%.", "contents": "Inhibition of evoked tongue jerks during the rat's cerebral ventricles perfusion with gamma-aminobutiric acid and beta-phenyl-gamma-aminobutiric acid. The supraorbital branch of the trigeminal nerve of rats in chloralose anaesthesia was stimulated with electrical pulses. The stimulation of the afferent fibres of the trigeminal nerve evoked the retractive jerks of the outstretched tongue. These evoked tongue jerks (ETJ) were recorded on the tape of the line recorder through an isotonic transducer. The caniulae were inserted into the lateral cerebral ventricles by means of streotaxic apparatus and perfusion was performed with inflow of GABA or beta-phenyl-GABA-containing fluid into the right lateral ventricle and outflow through the left lateral ventricle. Perfusion with solution of 0.01 mol/l GABA reduced the amplitude of ETJ 25.9% while perfusion with hypertonic NaCl solution increased it by 19.5%, and perfusion with solution of 0.2 mol/l beta-phenyl-GABA reduced that amplitude by 39.9%."}
{"id": "PMID:212936", "title": "Brain tumours in the elderly.", "content": "The incidence of cerebral tumour in a geriatric department over a seven-year period was 0.9% of all admissions. The distribution of benign, malignant and secondary brain tumours and their histological types were similar to those of younger adults. Apart from small asymptomatic tumours found incidentally at post mortem, most symptomatic tumours were recognized from their characteristic history. In particular, only 0.4% of patients diagnosed as stroke were subsequently found to have a cerebral tumour.", "contents": "Brain tumours in the elderly. The incidence of cerebral tumour in a geriatric department over a seven-year period was 0.9% of all admissions. The distribution of benign, malignant and secondary brain tumours and their histological types were similar to those of younger adults. Apart from small asymptomatic tumours found incidentally at post mortem, most symptomatic tumours were recognized from their characteristic history. In particular, only 0.4% of patients diagnosed as stroke were subsequently found to have a cerebral tumour."}
{"id": "PMID:212937", "title": "Age changes in collagen characteristics of bone and skin of a short-lived species of reptile.", "content": "Decalcified bone collagen of older male garden lizards, Calotes versicolor, was less susceptible to digestion by collagenase from Clostridium histolyticum than that from younger individuals. In aged skin the percentage solubility and the soluble/insoluble collagen ratio decreased, with a concomitant rise in insoluble and total collagen. Collagen/unit area increased with advancing age in both dorsal and ventral skin. These results from a non-mammalian poikilothermic vertebrate provide additional evidence in favour of the cross-linkage theory of ageing and suggest a common pattern of collagen ageing in vertebrates.", "contents": "Age changes in collagen characteristics of bone and skin of a short-lived species of reptile. Decalcified bone collagen of older male garden lizards, Calotes versicolor, was less susceptible to digestion by collagenase from Clostridium histolyticum than that from younger individuals. In aged skin the percentage solubility and the soluble/insoluble collagen ratio decreased, with a concomitant rise in insoluble and total collagen. Collagen/unit area increased with advancing age in both dorsal and ventral skin. These results from a non-mammalian poikilothermic vertebrate provide additional evidence in favour of the cross-linkage theory of ageing and suggest a common pattern of collagen ageing in vertebrates."}
{"id": "PMID:212940", "title": "Osteoporosis: effects of calcium.", "content": "Bone loss coincides with the reduced physical activity of both sexes in later years, vigorously aggravated by age-associated hormonal changes in women and chronic inadequate intake of calcium. In the absence of preventive dietary measures, osteoporosis may become a major health problem for America's fastgrowing senior female population. Bone loss and fracture risk may be minimized or reversed by a daily intake of approximately 1 Gm. of calcium derived from the diet or through supplements.", "contents": "Osteoporosis: effects of calcium. Bone loss coincides with the reduced physical activity of both sexes in later years, vigorously aggravated by age-associated hormonal changes in women and chronic inadequate intake of calcium. In the absence of preventive dietary measures, osteoporosis may become a major health problem for America's fastgrowing senior female population. Bone loss and fracture risk may be minimized or reversed by a daily intake of approximately 1 Gm. of calcium derived from the diet or through supplements."}
{"id": "PMID:212941", "title": "C-type virus-lymphocyte interactions in developing mouse thymus.", "content": "The appearance of C-type virus particles in thymus cells of Swiss mouse embryos, 11.5 to 15.5 days post-conception age (PCA), was studied with the electron microscope. In thymic rudiments of all specimens examined, virus particles were seen in epithelial cytoplasm, budding from epithelial cell surfaces and in extracellular spaces. Lymphoid cells were first seen in thymic rudiments of 13.5 days PCA, and did not display virus particles at this stage. At 14.5 days PCA, thymic lymphocytes had localized plasmalemmal thickenings of high electron-density which were adjacent to extracellular virus particles. Viruses appeared to be penetrating thymic lymphocytes by viropexis in embryos of 15.5 days PCA. At this stage, many lymphocytes also had cytoplasmic virus-containing vesicles and viral buds at their surfaces. These observations suggest the possibility that, in embryos, C-type viruses are transmitted horizontally from thymic epithelium to early populations of thymic lymphocytes.", "contents": "C-type virus-lymphocyte interactions in developing mouse thymus. The appearance of C-type virus particles in thymus cells of Swiss mouse embryos, 11.5 to 15.5 days post-conception age (PCA), was studied with the electron microscope. In thymic rudiments of all specimens examined, virus particles were seen in epithelial cytoplasm, budding from epithelial cell surfaces and in extracellular spaces. Lymphoid cells were first seen in thymic rudiments of 13.5 days PCA, and did not display virus particles at this stage. At 14.5 days PCA, thymic lymphocytes had localized plasmalemmal thickenings of high electron-density which were adjacent to extracellular virus particles. Viruses appeared to be penetrating thymic lymphocytes by viropexis in embryos of 15.5 days PCA. At this stage, many lymphocytes also had cytoplasmic virus-containing vesicles and viral buds at their surfaces. These observations suggest the possibility that, in embryos, C-type viruses are transmitted horizontally from thymic epithelium to early populations of thymic lymphocytes."}
{"id": "PMID:212942", "title": "Specific subclones derived from a multipotential clone of rat anterior pituitary cells.", "content": "Several functional subclones of rat anterior pituitary cells were established from our 2A8 clone which apparently contains a heterogenous population of committed and uncommitted cells. On the basis of the hormones secreted into the culture media, as measured by radioimmunoassay, these subclones were divided into four categories, i.e., subclones which secrete (1) ACTH only, (2) prolactin only, (3) prolactin and GH or (4) ACTH, prolactin and GH. None of the subclones produced detectable amounts of thyrotrophic or gonadotrophic hormones. Subclones which secrete a single hormone have shown no change in the type of hormone produced, indicating that these subclones were each derived from a committed cell. The cells of all subclones exhibit a normal diploid karyotype and show good growth characteristics. The cells of the different subclones can be classified by phase contrast microscopy into four categories. However, no clear-cut ultrastructural features have been observed which can be correlated with the different categories of subclones. On the basis of the results a hypothesis is proposed relative to the functional cytodifferentiation of anterior pituitary cells.", "contents": "Specific subclones derived from a multipotential clone of rat anterior pituitary cells. Several functional subclones of rat anterior pituitary cells were established from our 2A8 clone which apparently contains a heterogenous population of committed and uncommitted cells. On the basis of the hormones secreted into the culture media, as measured by radioimmunoassay, these subclones were divided into four categories, i.e., subclones which secrete (1) ACTH only, (2) prolactin only, (3) prolactin and GH or (4) ACTH, prolactin and GH. None of the subclones produced detectable amounts of thyrotrophic or gonadotrophic hormones. Subclones which secrete a single hormone have shown no change in the type of hormone produced, indicating that these subclones were each derived from a committed cell. The cells of all subclones exhibit a normal diploid karyotype and show good growth characteristics. The cells of the different subclones can be classified by phase contrast microscopy into four categories. However, no clear-cut ultrastructural features have been observed which can be correlated with the different categories of subclones. On the basis of the results a hypothesis is proposed relative to the functional cytodifferentiation of anterior pituitary cells."}
{"id": "PMID:212944", "title": "Serum and lymph-node collagenase in sarcoidosis. Comparison with angiotensin-converting enzyme.", "content": "Serum collagenase was significantly elevated in stage II, but not stage I sarcoidosis, in contrast to elevation of serum angiotensin-converting enzyme in stages I and II. Neither serum collagenase nor angiotensin-converting enzyme was elevated in active tuberculosis. Elevated serum collagenase and angiotensin-converting enzyme levels were decreased with steroid therapy. Serum collagenase and angiotensin-converting enzyme were significantly correlated but did not vary identically. Collagenase was not elevated in lymph nodes in sarcoidosis, in contrast to marked elevation of angiotensin-converting enzyme. The results suggest that serum angiotensin-converting enzyme is a more sensitive index of sarcoidosis activity than serum collagenase, which may have an ancillary role in assessment of the disease.", "contents": "Serum and lymph-node collagenase in sarcoidosis. Comparison with angiotensin-converting enzyme. Serum collagenase was significantly elevated in stage II, but not stage I sarcoidosis, in contrast to elevation of serum angiotensin-converting enzyme in stages I and II. Neither serum collagenase nor angiotensin-converting enzyme was elevated in active tuberculosis. Elevated serum collagenase and angiotensin-converting enzyme levels were decreased with steroid therapy. Serum collagenase and angiotensin-converting enzyme were significantly correlated but did not vary identically. Collagenase was not elevated in lymph nodes in sarcoidosis, in contrast to marked elevation of angiotensin-converting enzyme. The results suggest that serum angiotensin-converting enzyme is a more sensitive index of sarcoidosis activity than serum collagenase, which may have an ancillary role in assessment of the disease."}
{"id": "PMID:212945", "title": "Fibrous histiocytoma of the trachea.", "content": "The light and electron microscopic features of a fibrous histiocytoma of the trachea that occurred in a 15-year-old Caucasian girl are presented. Emphasis is placed on the aggresive behavior and the importance of early recognition of the lesion in an unusual location.", "contents": "Fibrous histiocytoma of the trachea. The light and electron microscopic features of a fibrous histiocytoma of the trachea that occurred in a 15-year-old Caucasian girl are presented. Emphasis is placed on the aggresive behavior and the importance of early recognition of the lesion in an unusual location."}
{"id": "PMID:212948", "title": "Detection of early \"significant\" antibody responses in paired sera by the use of an automated bovine parainfluenza-3 hemagglutination-inhibition system.", "content": "An automated bovine parainfluenza-3 hemagglutination-inhibition system was used to detect small increases (15--20%) in specific antibody titer between paired bovine sera collected three days apart. Automated and manual parainfluenza-3 hemagglutination-inhibition test procedures were compared as methods for the serologic diagnosis of parainfluenza-3 infection. Fifteen daily serum specimens from each of three animals were analyzed as various possible manual-test and automated-test serum pairs. With the sera from two of the animals, considered to be parainfluenza-3 hemagglutination-inhibition-positive, the manual microtiter test procedure made 18 (69%) false negative diagnoses when using the standard manual-test criteria for \"evidence of infection.\" When a 20% titer increase between three-day serum pairs was considered \"serologically significant,\" the automated system made three (17%) false-negative diagnoses. At a 15% \"serologically significant\" increase, no false-negative diagnosis was made. The utilization of automated serology for the routine diagnosis of disease should permit treatment and control measures to be initiated early, thereby reducing losses due to infectious disease.", "contents": "Detection of early \"significant\" antibody responses in paired sera by the use of an automated bovine parainfluenza-3 hemagglutination-inhibition system. An automated bovine parainfluenza-3 hemagglutination-inhibition system was used to detect small increases (15--20%) in specific antibody titer between paired bovine sera collected three days apart. Automated and manual parainfluenza-3 hemagglutination-inhibition test procedures were compared as methods for the serologic diagnosis of parainfluenza-3 infection. Fifteen daily serum specimens from each of three animals were analyzed as various possible manual-test and automated-test serum pairs. With the sera from two of the animals, considered to be parainfluenza-3 hemagglutination-inhibition-positive, the manual microtiter test procedure made 18 (69%) false negative diagnoses when using the standard manual-test criteria for \"evidence of infection.\" When a 20% titer increase between three-day serum pairs was considered \"serologically significant,\" the automated system made three (17%) false-negative diagnoses. At a 15% \"serologically significant\" increase, no false-negative diagnosis was made. The utilization of automated serology for the routine diagnosis of disease should permit treatment and control measures to be initiated early, thereby reducing losses due to infectious disease."}
{"id": "PMID:212949", "title": "Effect of premenopausal castration and incremental dosages of conjugated equine estrogens on plasma follicle-stimulating hormone, luteinizing hormone, and estradiol.", "content": "Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured serially in 11 premenopausal patients before and after hysterectomy with bilateral salpingo-oophorectomy. One week after operation an incremental dosage regimen of conjugated estrogens (CEE) in tablet form was commenced on a basis of two weeks with therapy (0.3, 0.625, 1.25, and finally 2.5 mg.), with each dose interspersed by two weeks without therapy. FSH, LH and E2 levels were measured at the end of each period with and without therapy. E2 levels fell within 24 hours of operation while FSH and LH levels rose gradually. CEE therapy produced an elevation of E2, but circulating concentrations comparable to the premenopausal values were only maintained during the dosage periods of 0.625 and 1.25 mg. of CEE. In only one instance did CEE succeed in reducing FSH to premenopausal levels, and that was at a dosage of 2.5 mg., in which instance the E2 level was higher than the premenopausal value. LH was never reduced to a premenopausal level. Thus, the data indicate that CEE alone in dosages up to 2.5 mg. per day was unable to reproduce in postmenopausal women the gonadotropin and E2 blood serum levels shown to exist prior to oophorectomy. Usual CEE treatment after menopause, therefore, in itself does not represent physiologic \"hormone replacement therapy,\" if defined as the dosage required to maintain premenopausal circulating concentrations of reproductive hormones.", "contents": "Effect of premenopausal castration and incremental dosages of conjugated equine estrogens on plasma follicle-stimulating hormone, luteinizing hormone, and estradiol. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured serially in 11 premenopausal patients before and after hysterectomy with bilateral salpingo-oophorectomy. One week after operation an incremental dosage regimen of conjugated estrogens (CEE) in tablet form was commenced on a basis of two weeks with therapy (0.3, 0.625, 1.25, and finally 2.5 mg.), with each dose interspersed by two weeks without therapy. FSH, LH and E2 levels were measured at the end of each period with and without therapy. E2 levels fell within 24 hours of operation while FSH and LH levels rose gradually. CEE therapy produced an elevation of E2, but circulating concentrations comparable to the premenopausal values were only maintained during the dosage periods of 0.625 and 1.25 mg. of CEE. In only one instance did CEE succeed in reducing FSH to premenopausal levels, and that was at a dosage of 2.5 mg., in which instance the E2 level was higher than the premenopausal value. LH was never reduced to a premenopausal level. Thus, the data indicate that CEE alone in dosages up to 2.5 mg. per day was unable to reproduce in postmenopausal women the gonadotropin and E2 blood serum levels shown to exist prior to oophorectomy. Usual CEE treatment after menopause, therefore, in itself does not represent physiologic \"hormone replacement therapy,\" if defined as the dosage required to maintain premenopausal circulating concentrations of reproductive hormones."}
{"id": "PMID:212950", "title": "Neurological disorders and pregnancy.", "content": "Certain neurological disorders are particularly liable to occur during pregnancy or may be profoundly influenced by it. Moreover, neurological disorders may influence the management of otherwise uncomplicated obstetric cases. Despite the practical importance of this subject, however, little attention has been devoted to it in the literature. Moreover, those papers that have been published are widely disseminated and so are not easily accessible to the many practicing physicians who may be confronted with a clinical problem of this sort. In this communication, a succinct account is provided of the interrelationship between noneclamptic pregnancy and maternal neurological disorders, with emphasis being placed on aspects that are of practical significance in a clinical context. The treatment of neurological disorders that are likely to pose a problem during pregnancy is discussed, and the manner in which these disorders may influence obstetric management is reviewed.", "contents": "Neurological disorders and pregnancy. Certain neurological disorders are particularly liable to occur during pregnancy or may be profoundly influenced by it. Moreover, neurological disorders may influence the management of otherwise uncomplicated obstetric cases. Despite the practical importance of this subject, however, little attention has been devoted to it in the literature. Moreover, those papers that have been published are widely disseminated and so are not easily accessible to the many practicing physicians who may be confronted with a clinical problem of this sort. In this communication, a succinct account is provided of the interrelationship between noneclamptic pregnancy and maternal neurological disorders, with emphasis being placed on aspects that are of practical significance in a clinical context. The treatment of neurological disorders that are likely to pose a problem during pregnancy is discussed, and the manner in which these disorders may influence obstetric management is reviewed."}
{"id": "PMID:212951", "title": "Diagnosis of Sheehan's syndrome using a sequential pituitary stimulation test.", "content": "Systematic pituitary evaluation was performed in four patients suspected of having Sheehan's syndrome. A sequential pituitary stimulation test, consisting of insulin-induced hypoglycemia followed by stimulation of gonadotropin-(GnRH) and thyroid-releasing hormone (TRH), a metyrapone test, and adrenocorticotropic hormone (ACTH) stimulation test, was performed. All four patients failed to develop a normal increase in serum growth hormone, cortisol, and prolactin (PRL) following insulin-induced hypoglycemia. All patients demonstrated a blunted PRL, follicle-stimulating hormone, and luteinizing hormone response to the combination of GnRH and TRH. Although thyroid stimulating hormone (TSH) response was impaired in all patients, two patients had normal T3 resin uptake and thyroxine, demonstrating minimal TSH reserve maintaining normal baseline free thyroxine index. Metyrapone administration was followed by no increase in 11-deoxycortisol or 17-ketogenic steroids, thereby adding no additional information to the hypoglycemia stimulation. ACTH infusion revealed normal adrenal cortisol response. In conclusion, in patients with suspected postpartum hypopituitarism, a complete pituitary function investigation can be done in a short time by using the described pituitary sequential stimulation test.", "contents": "Diagnosis of Sheehan's syndrome using a sequential pituitary stimulation test. Systematic pituitary evaluation was performed in four patients suspected of having Sheehan's syndrome. A sequential pituitary stimulation test, consisting of insulin-induced hypoglycemia followed by stimulation of gonadotropin-(GnRH) and thyroid-releasing hormone (TRH), a metyrapone test, and adrenocorticotropic hormone (ACTH) stimulation test, was performed. All four patients failed to develop a normal increase in serum growth hormone, cortisol, and prolactin (PRL) following insulin-induced hypoglycemia. All patients demonstrated a blunted PRL, follicle-stimulating hormone, and luteinizing hormone response to the combination of GnRH and TRH. Although thyroid stimulating hormone (TSH) response was impaired in all patients, two patients had normal T3 resin uptake and thyroxine, demonstrating minimal TSH reserve maintaining normal baseline free thyroxine index. Metyrapone administration was followed by no increase in 11-deoxycortisol or 17-ketogenic steroids, thereby adding no additional information to the hypoglycemia stimulation. ACTH infusion revealed normal adrenal cortisol response. In conclusion, in patients with suspected postpartum hypopituitarism, a complete pituitary function investigation can be done in a short time by using the described pituitary sequential stimulation test."}
{"id": "PMID:212952", "title": "Oral administration of theophylline to modify pressor responsiveness to angiotensin II in women with pregnancy-induced hypertension.", "content": "Normally, women become refractory to the pressor effects of infused angiotensin-II (A-II) early in pregnancy. Gravid women destined to develop pregnancy-induced hypertension (PIH) lose this refractoriness to A-II several weeks prior to the detection of hypertension. Normal pregnant women also lose their A-II refractoriness after treatment with prostaglandin synthetase inhibitors and, in this regard become similar to gravid women who are destined to develop PIH. From this observation, we have concluded that a prostaglandin(s) or a prostaglandin-related substance(s) is likely involved in the mediation of vascular reactivity to A-II during pregnancy. The present study was conducted to ascertain if control of vascular reactivity during pregnancy also involves the cyclic nucleotides. Since theophylline is known to inhibit the action of phosphodiesterase, an action that results in increased cellular levels of cyclic 3',5'-adenosine monophosphate (cAMP), we evaluated the effective pressor dose of A-II before and after the administration of theophylline to women with mild PIH who were beyond the 28th week of gestation. The effective pressor dose of A-II in these women with PIH before theophylline treatment was 7.3 +/- 1.4 ng. times kg.(-1) times min.(-1) (mean and standard error). Following treatment of these women with the equivalent of 500 mg. of theophylline daily for four days, the effective pressor dose of A-II was 16.7 +/- 3.8 ng. times kg.(-1) times min.(-1) (p less than 0.025). These findings are consistent with the view that a prostaglandin(s) synthesized in the arteriole may modulate the vascular refractoriness to A-II by altering the intracellular level of cAMP in vascular tissues.", "contents": "Oral administration of theophylline to modify pressor responsiveness to angiotensin II in women with pregnancy-induced hypertension. Normally, women become refractory to the pressor effects of infused angiotensin-II (A-II) early in pregnancy. Gravid women destined to develop pregnancy-induced hypertension (PIH) lose this refractoriness to A-II several weeks prior to the detection of hypertension. Normal pregnant women also lose their A-II refractoriness after treatment with prostaglandin synthetase inhibitors and, in this regard become similar to gravid women who are destined to develop PIH. From this observation, we have concluded that a prostaglandin(s) or a prostaglandin-related substance(s) is likely involved in the mediation of vascular reactivity to A-II during pregnancy. The present study was conducted to ascertain if control of vascular reactivity during pregnancy also involves the cyclic nucleotides. Since theophylline is known to inhibit the action of phosphodiesterase, an action that results in increased cellular levels of cyclic 3',5'-adenosine monophosphate (cAMP), we evaluated the effective pressor dose of A-II before and after the administration of theophylline to women with mild PIH who were beyond the 28th week of gestation. The effective pressor dose of A-II in these women with PIH before theophylline treatment was 7.3 +/- 1.4 ng. times kg.(-1) times min.(-1) (mean and standard error). Following treatment of these women with the equivalent of 500 mg. of theophylline daily for four days, the effective pressor dose of A-II was 16.7 +/- 3.8 ng. times kg.(-1) times min.(-1) (p less than 0.025). These findings are consistent with the view that a prostaglandin(s) synthesized in the arteriole may modulate the vascular refractoriness to A-II by altering the intracellular level of cAMP in vascular tissues."}
{"id": "PMID:212953", "title": "Fetal lung maturation: human amniotic fluid phosphatidate phosphohydrolase activity through normal gestation and its relation to the lecithin/sphingomyelin ratio.", "content": "In order to evaluate the relationship between the increase in amniotic fluid phosphatidate phosphohydrolase (PAPase) specific activity and the increase in the lecithin/sphingomyelin (L/S) ratio during normal human pregnancy, PAPase specific activity and the L/S ratio were measured in 171 amniotic fluid samples obtained from 164 women who were at 17 to 42 weeks' gestation. The increase in PAPase specific activity in amniotic fluid is parallel to the increase in the L/S ratio. The correlation between PAPase specific activity and the L/S ratio in amniotic fluid from all gestational ages is highly significant. The relationship of PAPase specific activity in amniotic fluid to PAPase specific activity in gastric fluid was investigated in a study of 97 newborn infants. A highly significant correlation was found between these two values. To ascertain if a relationship exists between the specific activity of PAPase in amniotic fluid and the subsequent development of hyaline membrane disease (HMD), 223 neonates who were delivered within 72 hours of amniotic fluid collection were studied. Only one infant developed HMD out of 170 with amniotic fluid PAPase specific activity equal to or greater than 50 nmoles of orthophosphate released X mg.-1 of protein X hr.-1. On the other hand, the finding of an amniotic fluid PAPase specific activity of less than 50 nmoles was of little value in predicting lung immaturity. We believe that these findings are also supportive of the view that PAPase and surfactant are released from the type II pneumocyte as a closely related structural unit, viz., the lamellar body.", "contents": "Fetal lung maturation: human amniotic fluid phosphatidate phosphohydrolase activity through normal gestation and its relation to the lecithin/sphingomyelin ratio. In order to evaluate the relationship between the increase in amniotic fluid phosphatidate phosphohydrolase (PAPase) specific activity and the increase in the lecithin/sphingomyelin (L/S) ratio during normal human pregnancy, PAPase specific activity and the L/S ratio were measured in 171 amniotic fluid samples obtained from 164 women who were at 17 to 42 weeks' gestation. The increase in PAPase specific activity in amniotic fluid is parallel to the increase in the L/S ratio. The correlation between PAPase specific activity and the L/S ratio in amniotic fluid from all gestational ages is highly significant. The relationship of PAPase specific activity in amniotic fluid to PAPase specific activity in gastric fluid was investigated in a study of 97 newborn infants. A highly significant correlation was found between these two values. To ascertain if a relationship exists between the specific activity of PAPase in amniotic fluid and the subsequent development of hyaline membrane disease (HMD), 223 neonates who were delivered within 72 hours of amniotic fluid collection were studied. Only one infant developed HMD out of 170 with amniotic fluid PAPase specific activity equal to or greater than 50 nmoles of orthophosphate released X mg.-1 of protein X hr.-1. On the other hand, the finding of an amniotic fluid PAPase specific activity of less than 50 nmoles was of little value in predicting lung immaturity. We believe that these findings are also supportive of the view that PAPase and surfactant are released from the type II pneumocyte as a closely related structural unit, viz., the lamellar body."}
{"id": "PMID:212954", "title": "Desoxycorticosterone in normal pregnancy. I. Sequential studies of the secretory patterns of desoxycorticosterone, aldosterone, and cortisol.", "content": "Plasma concentrations of desoxycorticosterone (DOC) and aldosterone are markedly elevated in pregnancy. Although DOC secretion in nongravid women has been assumed to be dependent mainly on adrenocorticotropic hormone (ACTH), in a previous study of women in the third trimester of pregnancy it was found to be unresponsive to ACTH, dexamethasone, and variations in salt intake. In this study plasma DOC, aldosterone, and cortisol levels, as well as their responses to ACTH stimulation and overnight dexamethasone suppression, were observed sequentially in seven normal women during the course of pregnancy and at three months post partum. Plasma DOC, aldosterone, and cortisol levels rose substantially during gestation, but increments in DOC did not necessarily coincide with those of the other two. Responses of all three corticosteroids to ACTH were enhanced during the first two trimesters compared to the nongravid state; DOC became unresponsive in the third trimester, while aldosterone and cortisol rose to an even greater extent. Elevated maternal DOC was not decreased significantly by dexamethasone at any stage of pregnancy, while plasma cortisol was suppressed. Nonsuppressibility of DOC with dexamethasone and also the lack of correlation of the rise in DOC with the increase in cortisol during the course of pregnancy suggest that increased DOC secretion in pregnancy does not arise from ACTH-dependent pathways of the maternal adrenal. The loss of responsiveness of DOC to ACTH in the third trimester suggests that the maternal adrenals have undergone an alteration in their steroidogenic response to ACTH, but also may indicate that their output of DOC has reached a maximal rate.", "contents": "Desoxycorticosterone in normal pregnancy. I. Sequential studies of the secretory patterns of desoxycorticosterone, aldosterone, and cortisol. Plasma concentrations of desoxycorticosterone (DOC) and aldosterone are markedly elevated in pregnancy. Although DOC secretion in nongravid women has been assumed to be dependent mainly on adrenocorticotropic hormone (ACTH), in a previous study of women in the third trimester of pregnancy it was found to be unresponsive to ACTH, dexamethasone, and variations in salt intake. In this study plasma DOC, aldosterone, and cortisol levels, as well as their responses to ACTH stimulation and overnight dexamethasone suppression, were observed sequentially in seven normal women during the course of pregnancy and at three months post partum. Plasma DOC, aldosterone, and cortisol levels rose substantially during gestation, but increments in DOC did not necessarily coincide with those of the other two. Responses of all three corticosteroids to ACTH were enhanced during the first two trimesters compared to the nongravid state; DOC became unresponsive in the third trimester, while aldosterone and cortisol rose to an even greater extent. Elevated maternal DOC was not decreased significantly by dexamethasone at any stage of pregnancy, while plasma cortisol was suppressed. Nonsuppressibility of DOC with dexamethasone and also the lack of correlation of the rise in DOC with the increase in cortisol during the course of pregnancy suggest that increased DOC secretion in pregnancy does not arise from ACTH-dependent pathways of the maternal adrenal. The loss of responsiveness of DOC to ACTH in the third trimester suggests that the maternal adrenals have undergone an alteration in their steroidogenic response to ACTH, but also may indicate that their output of DOC has reached a maximal rate."}
{"id": "PMID:212964", "title": "Alterations in hepatic fine structure after chronic exposure of rats to dexamethasone.", "content": "The objective of this study was to determine the effects of chronic dexamethasone (DEX) administration on hepatic ultrastructure and to correlate these changes with plasma lipoprotein levels. Electron microscopic studies were made of hepatocytes from male rats killed 1, 3 and 5 days after DEX (2 mg, twice per day) administration. Three days after treatment plasma lipoprotein levels were highest and hepatocytes contained regions of the cytosome rich in elements of the smooth endoplasmic reticulum (SER). Osmiophilic particles were present in the tubules and vesicles of the SER, in the saccules and vacuoles of the Golgi complex, in secretory vesicles near the cell surface and in the space of Disse. DEX treatments also caused hepatocytes to accumulate tightly packed masses of beta-particles of glycogen in some regions of the cell while other areas displayed dispersed glycogen particles that were associated with the SER. These observations are consistent with the hypothesis that glucocorticoids 1. cause an elevation of plasma lipoprotein levels by increasing hepatic synthesis and secretion of VLDL, which involves the sequential participation of the ER, the Golgi complex and exocytosis of VLDL-containing vacuoles into the space of Disse, and 2. produce a change in the nature of the association of glycogen particles with the SER membranes in response to the physiological state of the animal.", "contents": "Alterations in hepatic fine structure after chronic exposure of rats to dexamethasone. The objective of this study was to determine the effects of chronic dexamethasone (DEX) administration on hepatic ultrastructure and to correlate these changes with plasma lipoprotein levels. Electron microscopic studies were made of hepatocytes from male rats killed 1, 3 and 5 days after DEX (2 mg, twice per day) administration. Three days after treatment plasma lipoprotein levels were highest and hepatocytes contained regions of the cytosome rich in elements of the smooth endoplasmic reticulum (SER). Osmiophilic particles were present in the tubules and vesicles of the SER, in the saccules and vacuoles of the Golgi complex, in secretory vesicles near the cell surface and in the space of Disse. DEX treatments also caused hepatocytes to accumulate tightly packed masses of beta-particles of glycogen in some regions of the cell while other areas displayed dispersed glycogen particles that were associated with the SER. These observations are consistent with the hypothesis that glucocorticoids 1. cause an elevation of plasma lipoprotein levels by increasing hepatic synthesis and secretion of VLDL, which involves the sequential participation of the ER, the Golgi complex and exocytosis of VLDL-containing vacuoles into the space of Disse, and 2. produce a change in the nature of the association of glycogen particles with the SER membranes in response to the physiological state of the animal."}
{"id": "PMID:212968", "title": "Biochemical and physiologic changes in lungs of rats exposed to a cadmium chloride aerosol.", "content": "The purpose of this study was to examine the in vivo effects of acute exposure to a cadmium chloride aerosol on the activity of pulmonary enzymes and selected physiologic parameters that are altered by exposure to oxidant agents. Male rats were exposed for 1 hour to 0.5 per cent aerosol of cadmium chloride. At 1,5, and 11 days after exposure to cadmium chloride, exposed rats compared to control rats (data expressed as per cent of control values) had lung-to-body weight ratios of 192, 174, and 140 per cent; lung glucose-6-phosphate dehydrogenase activities of 90, 107, and 135 per cent; lung superoxide dismutase activities of 96, 101, and 132 per cent; tidal volumes of 62, 63, and 89 per cent; respiratory frequencies of 170, 145, and 108 per cent; and lung weight-specific static deflation volumes at 30 cm water of 30, 13, and 31 per cent. A zero-order clearance of cadmium from whole lung was observed, with a half-time of 27.4 days. Light microscopic examination of lung tissue revealed initial pulmonary edema on day 1 that progressed to interstitial pneumonitis on day 5, with some recovery by 11 days after exposure. The cadmium induced biochemical, physiologic, and pathologic alterations were similar to the responses observed in lungs of rats exposed to a wide variety of pulmonary irritants; thus, the changes observed may represent a nonspecific response to tissue injury.", "contents": "Biochemical and physiologic changes in lungs of rats exposed to a cadmium chloride aerosol. The purpose of this study was to examine the in vivo effects of acute exposure to a cadmium chloride aerosol on the activity of pulmonary enzymes and selected physiologic parameters that are altered by exposure to oxidant agents. Male rats were exposed for 1 hour to 0.5 per cent aerosol of cadmium chloride. At 1,5, and 11 days after exposure to cadmium chloride, exposed rats compared to control rats (data expressed as per cent of control values) had lung-to-body weight ratios of 192, 174, and 140 per cent; lung glucose-6-phosphate dehydrogenase activities of 90, 107, and 135 per cent; lung superoxide dismutase activities of 96, 101, and 132 per cent; tidal volumes of 62, 63, and 89 per cent; respiratory frequencies of 170, 145, and 108 per cent; and lung weight-specific static deflation volumes at 30 cm water of 30, 13, and 31 per cent. A zero-order clearance of cadmium from whole lung was observed, with a half-time of 27.4 days. Light microscopic examination of lung tissue revealed initial pulmonary edema on day 1 that progressed to interstitial pneumonitis on day 5, with some recovery by 11 days after exposure. The cadmium induced biochemical, physiologic, and pathologic alterations were similar to the responses observed in lungs of rats exposed to a wide variety of pulmonary irritants; thus, the changes observed may represent a nonspecific response to tissue injury."}
{"id": "PMID:212971", "title": "Correlation of clinical and virus-specific immune responses following levamisole therapy of recurrent herpes progenitalis.", "content": "Patients with herpes progenitalis recurring every 14--28 days were treated with levamisole 150 mg orally twice weekly in an open trial to evaluate the relationship between immunomodulation and clinical response. Eight of 12 patients studied for 4--9 months reported a decrease in the frequency of recurrences. Enhanced virus-specific lymphoproliferative responses were observed in six of eight patients reporting clinical improvement. Herpes-antigen-induced production of leucocyte migration inhibitory factor (LMIF) was similarly enhanced in these individuals. In the four patients reporting no improvement, virus-specific lymphoproliferative and LMIF-generating responses were either depressed or unchanged. No significant alterations in neutralizing antibody titers were observed in any of the patients. Alterations in virus-specific lymphocyte transformation and lymphokine generation observed in vitro thus correlate with changes in clinical course in a manner consistent with the proposed immunomodulatory function of levamisole.", "contents": "Correlation of clinical and virus-specific immune responses following levamisole therapy of recurrent herpes progenitalis. Patients with herpes progenitalis recurring every 14--28 days were treated with levamisole 150 mg orally twice weekly in an open trial to evaluate the relationship between immunomodulation and clinical response. Eight of 12 patients studied for 4--9 months reported a decrease in the frequency of recurrences. Enhanced virus-specific lymphoproliferative responses were observed in six of eight patients reporting clinical improvement. Herpes-antigen-induced production of leucocyte migration inhibitory factor (LMIF) was similarly enhanced in these individuals. In the four patients reporting no improvement, virus-specific lymphoproliferative and LMIF-generating responses were either depressed or unchanged. No significant alterations in neutralizing antibody titers were observed in any of the patients. Alterations in virus-specific lymphocyte transformation and lymphokine generation observed in vitro thus correlate with changes in clinical course in a manner consistent with the proposed immunomodulatory function of levamisole."}
{"id": "PMID:212974", "title": "Comparison of the development of resistant strains of Type 1 herpes simplex virus to in vitro antiviral activity of 5-iodo-2'-deoxyuridine or ribavirin.", "content": "Exposure of HSV/1 to low concentrations of ribavirin during 4--5 passages does not produce ribavirin-resistant virus. IDU resistance was developed by HSV/1 while it was being passed simultaneously. This resistance was seen to develop in both KB and Vero cells. The IDU-resistant virus is also resistant to ribavirin in KB cells.", "contents": "Comparison of the development of resistant strains of Type 1 herpes simplex virus to in vitro antiviral activity of 5-iodo-2'-deoxyuridine or ribavirin. Exposure of HSV/1 to low concentrations of ribavirin during 4--5 passages does not produce ribavirin-resistant virus. IDU resistance was developed by HSV/1 while it was being passed simultaneously. This resistance was seen to develop in both KB and Vero cells. The IDU-resistant virus is also resistant to ribavirin in KB cells."}
{"id": "PMID:212976", "title": "Effect of ribavirin on Type 2 Herpesvirus hominis (HVH/2) in vitro and in vivo.", "content": "Ribavirin was found to inhibit five strains of HVH/2 tested in KB cells with the M1C range being 10-100 microgram/ml. In a mouse tail animal model, it effectively reduced HVH/2-induced lesions particularly at the peak lesion periods. Ribavirin was remarkably effective when intravaginal treatment was initiated late in the infection, which suggests that it may have potential for treatment of human cutaneous infections.", "contents": "Effect of ribavirin on Type 2 Herpesvirus hominis (HVH/2) in vitro and in vivo. Ribavirin was found to inhibit five strains of HVH/2 tested in KB cells with the M1C range being 10-100 microgram/ml. In a mouse tail animal model, it effectively reduced HVH/2-induced lesions particularly at the peak lesion periods. Ribavirin was remarkably effective when intravaginal treatment was initiated late in the infection, which suggests that it may have potential for treatment of human cutaneous infections."}
{"id": "PMID:212978", "title": "Antiviral potential of phosphonoacetic acid.", "content": "Phosphonoacetate has been found to inhibit specifically the replication of herpes-viruses. A partial inhibition of vaccinia virus represents the only activity outside the herpesvirus class. The drug was found to be a specific inhibitor of the virus-induced DNA polymerases. Normal cellular polymerases were relatively insensitive to phosphonoacetate, resulting in low cellular toxicity. Our working hypothesis is that the drug binds to the enzyme and that initiation of polynucleotide synthesis occurs in the presence of the drug and the required template, substrates, and cations. However, addition of deoxynucleosides to the elongating nascent chain is prevented by the enzyme-bound drug. Kinetic analyses indicated that phosphonoacetate did not interfere with the binding of DNA template to polymerase; and it did not compete with nucleotide substrate binding. The highly specific inhibitory effects of phosphonoacetate allowed for the selection of partially resistant strains of HSV. Resistance of virus to the drug in cell culture was directly correlated with the same relative resistance of the corresponding cell-free DNA polymerases. Phosphonoacetate was also effective therapeutically in herpesvirus skin and ocular infections in animals. Intraperitoneal administration of the drug reduced death and severity of disease in experimental encephalitis in hamsters. High specificity, low toxicity, and reproducible efficacy in lower animals suggested that phosphonoacetate could be a useful new antiviral drug. Sensitivity to phosphonoacetate also is a useful research tool as a genetic marker for herpesviruses.", "contents": "Antiviral potential of phosphonoacetic acid. Phosphonoacetate has been found to inhibit specifically the replication of herpes-viruses. A partial inhibition of vaccinia virus represents the only activity outside the herpesvirus class. The drug was found to be a specific inhibitor of the virus-induced DNA polymerases. Normal cellular polymerases were relatively insensitive to phosphonoacetate, resulting in low cellular toxicity. Our working hypothesis is that the drug binds to the enzyme and that initiation of polynucleotide synthesis occurs in the presence of the drug and the required template, substrates, and cations. However, addition of deoxynucleosides to the elongating nascent chain is prevented by the enzyme-bound drug. Kinetic analyses indicated that phosphonoacetate did not interfere with the binding of DNA template to polymerase; and it did not compete with nucleotide substrate binding. The highly specific inhibitory effects of phosphonoacetate allowed for the selection of partially resistant strains of HSV. Resistance of virus to the drug in cell culture was directly correlated with the same relative resistance of the corresponding cell-free DNA polymerases. Phosphonoacetate was also effective therapeutically in herpesvirus skin and ocular infections in animals. Intraperitoneal administration of the drug reduced death and severity of disease in experimental encephalitis in hamsters. High specificity, low toxicity, and reproducible efficacy in lower animals suggested that phosphonoacetate could be a useful new antiviral drug. Sensitivity to phosphonoacetate also is a useful research tool as a genetic marker for herpesviruses."}
{"id": "PMID:212980", "title": "Inhibition of herpesvirus DNA synthesis by 9-beta-D-arabinofuranosyladenine in cellular and cell-free systems.", "content": "9-beta-D-Arabinofuranosyladenine 5'-triphosphate (ara-ATP) is an inhibitor both of DNA polymerase-alpha and -beta from noninfected rabbit kidney cells and of the DNA-dependent DNA polymerase induced by herpes simplex virus Type 1 (strain IES). The studies were performed with partially purified enzymes, and each of the different polymerase preparations contained only one DNA-dependent DNA polymerase species. These enzymes were inhibited in a competitive manner. The HSV-induced DNA-dependent DNA polymerase was 39-fold more sensitive to ara-ATP than was cellular DNA polymerase-beta and 116-fold more sensitive than cellular DNA polymerase-alpha. The affinity of the HSV-induced enzyme for ara-ATP was only slightly influenced by the use of different template/initiators in the enzyme assays. In intact cell systems DNA synthesis was affected by 9-beta-D-arabinofuranosyladenine (ara-A) as indicated by the reduced incorporation of deoxythymidine. In herpesvirus-(strain Lennette)-infected cells, however, ara-A shows no influence on the incorporation on deoxythymidine into cellular DNA, but it substantially reduces the incorporation into viral DNA. Ara-A itself is incorporated into both cellular and herpesviral (strain Lennette, D-316 and IES) DNA during DNA synthesis.", "contents": "Inhibition of herpesvirus DNA synthesis by 9-beta-D-arabinofuranosyladenine in cellular and cell-free systems. 9-beta-D-Arabinofuranosyladenine 5'-triphosphate (ara-ATP) is an inhibitor both of DNA polymerase-alpha and -beta from noninfected rabbit kidney cells and of the DNA-dependent DNA polymerase induced by herpes simplex virus Type 1 (strain IES). The studies were performed with partially purified enzymes, and each of the different polymerase preparations contained only one DNA-dependent DNA polymerase species. These enzymes were inhibited in a competitive manner. The HSV-induced DNA-dependent DNA polymerase was 39-fold more sensitive to ara-ATP than was cellular DNA polymerase-beta and 116-fold more sensitive than cellular DNA polymerase-alpha. The affinity of the HSV-induced enzyme for ara-ATP was only slightly influenced by the use of different template/initiators in the enzyme assays. In intact cell systems DNA synthesis was affected by 9-beta-D-arabinofuranosyladenine (ara-A) as indicated by the reduced incorporation of deoxythymidine. In herpesvirus-(strain Lennette)-infected cells, however, ara-A shows no influence on the incorporation on deoxythymidine into cellular DNA, but it substantially reduces the incorporation into viral DNA. Ara-A itself is incorporated into both cellular and herpesviral (strain Lennette, D-316 and IES) DNA during DNA synthesis."}
{"id": "PMID:212981", "title": "Arabinosyl-N6-hydroxyadenine: a new potent antivirus drug.", "content": "Abrabinosyl-N6-hydroxyadenine (ara-HA) was tested for its antiherpesvirus and immunosuppressive activities in vivo and in vitro. Mouse strains were used that had been shown earlier to be very susceptible to intraperitoneal (i.p.) or intracerebral (i.c.) inoculation of a virulent strain of herpes simplex virus Type 1 (HSV-1). Susceptible mice were inoculated i.p. or i.c. with a stock pool of HSV-1 and treated with ara-HA (i.p.) beginning at least 24 hr later. The mice were given a 10-day course of drugs and followed for at least 21 days. Similar experiments were carried out with ara-A for comparative purposes. Ara-HA was found to protect mice inoculated with HSV-1 significantly better than ara-A. Lower concentrations of drugs were required and a higher percentage survived. Later challenge of the ara-HA-treated mice with HSV-1 demonstrated that these mice had become immune to HSV-1, indicating that the immune system is not severely affected by this course of ara-HA. A 10-day course of ara-HA, which was found to protect mice from 100 LD50 of HSV-1, reduced the capacity of the mouse lymphocytes to respond to allogeneic cells only slightly. In vitro ara-HA inhibited HSV-1 replication as well as proliferation of lymphocytes exposed to mitogen.", "contents": "Arabinosyl-N6-hydroxyadenine: a new potent antivirus drug. Abrabinosyl-N6-hydroxyadenine (ara-HA) was tested for its antiherpesvirus and immunosuppressive activities in vivo and in vitro. Mouse strains were used that had been shown earlier to be very susceptible to intraperitoneal (i.p.) or intracerebral (i.c.) inoculation of a virulent strain of herpes simplex virus Type 1 (HSV-1). Susceptible mice were inoculated i.p. or i.c. with a stock pool of HSV-1 and treated with ara-HA (i.p.) beginning at least 24 hr later. The mice were given a 10-day course of drugs and followed for at least 21 days. Similar experiments were carried out with ara-A for comparative purposes. Ara-HA was found to protect mice inoculated with HSV-1 significantly better than ara-A. Lower concentrations of drugs were required and a higher percentage survived. Later challenge of the ara-HA-treated mice with HSV-1 demonstrated that these mice had become immune to HSV-1, indicating that the immune system is not severely affected by this course of ara-HA. A 10-day course of ara-HA, which was found to protect mice from 100 LD50 of HSV-1, reduced the capacity of the mouse lymphocytes to respond to allogeneic cells only slightly. In vitro ara-HA inhibited HSV-1 replication as well as proliferation of lymphocytes exposed to mitogen."}
{"id": "PMID:212982", "title": "The effect of cyclic nucleotides on virus infection.", "content": "The yield of influenza virus from infected primary chick kidney cells (PCKC) was enhanced by treatment with dcAMP. In addition, rapid serial passages of the virus in treated chick cells at low multiplicities did also exhibit maintenance of high virus titers. The action of dcAMP upon viral replication could be reproduced in the chick cells by treatment with various agents known to increase intracellular cAMP levels by differing mechanisms. Furthermore, an adrenergic component in the activation of the PCKC cAMP system is indicated by the effects of certain catecholamines on influenza virus yield. Dibutyryl cAMP was shown in the same host to inhibit multiplication of Herpesvirus hominis Type 2, and its effect on other cell-virus systems indicates that its action consists of some host-specific element(s).", "contents": "The effect of cyclic nucleotides on virus infection. The yield of influenza virus from infected primary chick kidney cells (PCKC) was enhanced by treatment with dcAMP. In addition, rapid serial passages of the virus in treated chick cells at low multiplicities did also exhibit maintenance of high virus titers. The action of dcAMP upon viral replication could be reproduced in the chick cells by treatment with various agents known to increase intracellular cAMP levels by differing mechanisms. Furthermore, an adrenergic component in the activation of the PCKC cAMP system is indicated by the effects of certain catecholamines on influenza virus yield. Dibutyryl cAMP was shown in the same host to inhibit multiplication of Herpesvirus hominis Type 2, and its effect on other cell-virus systems indicates that its action consists of some host-specific element(s)."}
{"id": "PMID:212984", "title": "The selective inhibition of viral DNA synthesis by chemotherapeutic agents: an indicator of clinical usefulness?", "content": "A cell culture system has been utilized to measure the effects of drugs on DNA synthesis in uninfected and HSV-(herpes simplex virus)-infected KB cells. DNA from HSV-infected cells was separated into viral and cellular components by isopycnic centrifugation in CsCl gradients. The amount of [3H]thymidine incorporated into acid-insoluble material was measured in the absence and presence of drugs. Dose-response relationships were established by linearly regressing the probit value of the percent inhibition DNA synthesis against the logarithm of drug concentration. Fifty percent inhibitory (I50) concentrations were interpolated from the corresponding regression lines for inhibition of the following: (i) DNA synthesis is uninfected KB cells, (ii) total DNA synthesis in HSV-infected KB cells (iii) cellular DNA synthesis in HSV-infected cells, and (iv) viral DNA synthesis in HSV-infected cells. We have derived an index (SI, selective index) that quantifies the preferential inhibition of viral or uninfected cellular DNA synthesis. This index can be expressed as SI = log10 I50 concentration for DNA synthesis in uninfected cells divided by I50 concentration for viral DNA synthesis in HSV-infected cells. The SI is positive if viral DNA synthesis is inhibited preferentially and negative if uninfected cellular DNA synthesis is more strongly inhibited. A positive SI value of 0.5 was obtained for the clinically useful antiviral drug arabinosyladenine (ara-A) and a value of 0.4 for its metabolite, arabinosylhypoxanthine (ara-H). Although the adenosine deaminase inhibitor coformycin greatly increased the potency of ara-A, the inhibitor did not increase the selectivity of the drug (SI = 0.3). Stallimycin (distimycin A) (SI = 0.3) and phosphonoacetic acid (SI = 0.3) were similarly effective in preferentially inhibiting the synthesis of HSV DNA. In contrast, arabinosylcytosine (ara-C) and ribavirin inhibited DNA synthesis in uninfected cells to a greater degree than viral DNA synthesis (SI = -0.5 and -1.9, respectively). An analysis of the advantages and limitations of this experimental procedure is made and the suggestion is offered that the in vitro determination of a drug's selective index may be a valid predictor of clinical usefulness.", "contents": "The selective inhibition of viral DNA synthesis by chemotherapeutic agents: an indicator of clinical usefulness? A cell culture system has been utilized to measure the effects of drugs on DNA synthesis in uninfected and HSV-(herpes simplex virus)-infected KB cells. DNA from HSV-infected cells was separated into viral and cellular components by isopycnic centrifugation in CsCl gradients. The amount of [3H]thymidine incorporated into acid-insoluble material was measured in the absence and presence of drugs. Dose-response relationships were established by linearly regressing the probit value of the percent inhibition DNA synthesis against the logarithm of drug concentration. Fifty percent inhibitory (I50) concentrations were interpolated from the corresponding regression lines for inhibition of the following: (i) DNA synthesis is uninfected KB cells, (ii) total DNA synthesis in HSV-infected KB cells (iii) cellular DNA synthesis in HSV-infected cells, and (iv) viral DNA synthesis in HSV-infected cells. We have derived an index (SI, selective index) that quantifies the preferential inhibition of viral or uninfected cellular DNA synthesis. This index can be expressed as SI = log10 I50 concentration for DNA synthesis in uninfected cells divided by I50 concentration for viral DNA synthesis in HSV-infected cells. The SI is positive if viral DNA synthesis is inhibited preferentially and negative if uninfected cellular DNA synthesis is more strongly inhibited. A positive SI value of 0.5 was obtained for the clinically useful antiviral drug arabinosyladenine (ara-A) and a value of 0.4 for its metabolite, arabinosylhypoxanthine (ara-H). Although the adenosine deaminase inhibitor coformycin greatly increased the potency of ara-A, the inhibitor did not increase the selectivity of the drug (SI = 0.3). Stallimycin (distimycin A) (SI = 0.3) and phosphonoacetic acid (SI = 0.3) were similarly effective in preferentially inhibiting the synthesis of HSV DNA. In contrast, arabinosylcytosine (ara-C) and ribavirin inhibited DNA synthesis in uninfected cells to a greater degree than viral DNA synthesis (SI = -0.5 and -1.9, respectively). An analysis of the advantages and limitations of this experimental procedure is made and the suggestion is offered that the in vitro determination of a drug's selective index may be a valid predictor of clinical usefulness."}
{"id": "PMID:212987", "title": "The inhibition of Rauscher leukemia virus and avian myeloblastosis virus DNA polymerases by anthracycline compounds.", "content": "Studies by other investigators have shown that adriamycin and daunorubicin exhibit antitumor and antiviral activity. A possible antiviral mechanism for the anthracycline compounds is the potent inhibition of viral DNA polymerases. Five anthracycline compounds were tested against purified Rauscher leukemia virus and avian myeloblastosis virus DNA polymerases. All compounds were found to be potent inhibitors of viral DNA polymerase activity. Inhibition was found to be primarily due to the planar ring structure (daunomycinone) common to all of these compounds. The degree of inhibition was dependent on the templates used: activated DNA, synthetic hybrids, poly(rA).dT12-18 and poly(rC).dG12-18, and the synthetic copolymer, poly(DA-dT). Alteration of the group substituent on the planar ring affected the degree of viral DNA polymerase inhibition. The inhibitory effects by anthracycline compounds appear to be relatively specific for viral polymerases.", "contents": "The inhibition of Rauscher leukemia virus and avian myeloblastosis virus DNA polymerases by anthracycline compounds. Studies by other investigators have shown that adriamycin and daunorubicin exhibit antitumor and antiviral activity. A possible antiviral mechanism for the anthracycline compounds is the potent inhibition of viral DNA polymerases. Five anthracycline compounds were tested against purified Rauscher leukemia virus and avian myeloblastosis virus DNA polymerases. All compounds were found to be potent inhibitors of viral DNA polymerase activity. Inhibition was found to be primarily due to the planar ring structure (daunomycinone) common to all of these compounds. The degree of inhibition was dependent on the templates used: activated DNA, synthetic hybrids, poly(rA).dT12-18 and poly(rC).dG12-18, and the synthetic copolymer, poly(DA-dT). Alteration of the group substituent on the planar ring affected the degree of viral DNA polymerase inhibition. The inhibitory effects by anthracycline compounds appear to be relatively specific for viral polymerases."}
{"id": "PMID:212990", "title": "Effect of a novel adenosine deaminase inhibitor (co-vidarabine, co-V) upon the antiviral activity in vitro and in vivo of vidarabine (Vira-Atm) for DNA virus replication.", "content": "A new potent inhibitor of adenosine deaminase (co-vidarabine) was used in combination studies with adenine arabinoside (vidarabine, Vira-ATM) to protect this purine nucleoside from enzymatic deamination to the more weakly active metabolite, hypoxanthine arabinoside. Comparing the combination to vidarabine alone, a significant increase (10-fold) of the antiviral activity of the combined drugs was observed against herpes and vaccinia viruses in tissue culture and subcutaneously, against cranial herpesvirus infections in mice. Several other investigators have also recently reported several-fold enhancement of vidarabine activity by newly described deaminase inhibitors. They observed that plaque formation by several large DNA-containing viruses (herpes, vaccinia, varicella zoster) and an RNA-containing oncogenic virus was markedly prevented by the combination compared to vidarabine alone. In animals, enhanced protection (increased survivors) and/or highly significant increase in the life span of dying mice treated with the 2-drug combination, was also observed compared to vidarabine administered singly. These observations in animals clearly indicate that combination studies with vidarabine (Vira-ATM) and co-vidarabine (deaminase inhibitor) deserve serious consideration as future therapy for systemic virus infections in man including herpesvirus encephalitis.", "contents": "Effect of a novel adenosine deaminase inhibitor (co-vidarabine, co-V) upon the antiviral activity in vitro and in vivo of vidarabine (Vira-Atm) for DNA virus replication. A new potent inhibitor of adenosine deaminase (co-vidarabine) was used in combination studies with adenine arabinoside (vidarabine, Vira-ATM) to protect this purine nucleoside from enzymatic deamination to the more weakly active metabolite, hypoxanthine arabinoside. Comparing the combination to vidarabine alone, a significant increase (10-fold) of the antiviral activity of the combined drugs was observed against herpes and vaccinia viruses in tissue culture and subcutaneously, against cranial herpesvirus infections in mice. Several other investigators have also recently reported several-fold enhancement of vidarabine activity by newly described deaminase inhibitors. They observed that plaque formation by several large DNA-containing viruses (herpes, vaccinia, varicella zoster) and an RNA-containing oncogenic virus was markedly prevented by the combination compared to vidarabine alone. In animals, enhanced protection (increased survivors) and/or highly significant increase in the life span of dying mice treated with the 2-drug combination, was also observed compared to vidarabine administered singly. These observations in animals clearly indicate that combination studies with vidarabine (Vira-ATM) and co-vidarabine (deaminase inhibitor) deserve serious consideration as future therapy for systemic virus infections in man including herpesvirus encephalitis."}
{"id": "PMID:212993", "title": "Ovarian neoplasia in ornamental hybrid carp (Nishikigoi) in Japan.", "content": "Massive abdominal enlargements were observed in 21 adult carp 4--6 years old living in the breeding ponds of carp fisheries in northern Japan. The abdominal enlargement rapidly increased, and the affected fish died within a few months. At necropsy, single or multiple tumors, 1.5--25 cm (average, 10.6 cm) in diameter, were found in the abdominal cavity. Ovarian tissue was identified close to the tumors in 15 cases, and there was no evidence of anatomic continuity between the tumors and other viscera. It seems likely that all of these tumors arose in the ovaries. Histologically, the 21 tumors observed exhibited great variation, but they were composed mainly of various types of cells similar to those of human dysgerminoma, granulosatheca cell tumors, or embryonal carcinomas. Squamous cell nests were found with mesenchymal elements in one tumor. Thus, ovarian tumors in carp may have diverse histogenetic origins and probably arise both from germ cells and from ovarian mesenchyme. Areas of cellular pleomorphism, which suggested a malignant character, were seen in some of the tumors, but no evidence on metastasis was found. Tumor-bearing carp had generally been raised in ponds supplied by wells or underground springs in mountainous areas. Evidence of a possible environmental factors(s) is yet to be demonstrated.", "contents": "Ovarian neoplasia in ornamental hybrid carp (Nishikigoi) in Japan. Massive abdominal enlargements were observed in 21 adult carp 4--6 years old living in the breeding ponds of carp fisheries in northern Japan. The abdominal enlargement rapidly increased, and the affected fish died within a few months. At necropsy, single or multiple tumors, 1.5--25 cm (average, 10.6 cm) in diameter, were found in the abdominal cavity. Ovarian tissue was identified close to the tumors in 15 cases, and there was no evidence of anatomic continuity between the tumors and other viscera. It seems likely that all of these tumors arose in the ovaries. Histologically, the 21 tumors observed exhibited great variation, but they were composed mainly of various types of cells similar to those of human dysgerminoma, granulosatheca cell tumors, or embryonal carcinomas. Squamous cell nests were found with mesenchymal elements in one tumor. Thus, ovarian tumors in carp may have diverse histogenetic origins and probably arise both from germ cells and from ovarian mesenchyme. Areas of cellular pleomorphism, which suggested a malignant character, were seen in some of the tumors, but no evidence on metastasis was found. Tumor-bearing carp had generally been raised in ponds supplied by wells or underground springs in mountainous areas. Evidence of a possible environmental factors(s) is yet to be demonstrated."}
{"id": "PMID:212994", "title": "Hepatomas and other neoplasms in the atlantic hagfish (Myxine glutinosa): a histopathologic and chemical study.", "content": "M. glutinosa is a cyclostome, living in the mud in seawater of high salinity. It probably is a stationary scavenger feeder. About 28,000 hagfish from the Gullmar Fjord were examined during a 5-year period for the occurrence of tumors. Hepatomas were found to be predominant neoplasm, observed at a frequency that decreased from 5.8% in 1972 to 2.9% in 1973 and finally to 0.6% in 1974--76. Islet cell hamartomas and frank neoplasms decreased from 0.5% in 1972 to less than 0.1% in 1973--76. Occasional subcutaneous and mesenterial neoplasms were also observed during 1972--74. In hagfish caught 12 km out in the open sea, the hepatoma incidence decreased from 2.8% in 1972 to 0.9% in 1974. Given this background, it is possible that pollution of the Gullmar Fjord by carcinogenic substances with low biodegradability has occurred until 1972, and this pollution could be of etiologic significance for these hagfish tumors. In fact, the use of PCBs became prohibited by law in Sweden in 1971--72. Severe restrictions were also introduced for the use of chlorinated pesticides, notably DDT, and associated substances (DDD, DDE). Preliminary analyses for the presence of PCBs, DDT (and its metabolites), and aflatoxins (the notorious hepatocarcinogen) were performed by gas chromatography and thin-layer chromatography. Livers (with and without neoplasms) from hagfish caught inside the threshold of the fjord contained about 5 mg/kg of wet weight of PCBs and about 0.1--0.4 mg/kg of dry weight of DDT, DDD, or DDE, whereas those from hagfish caught in the open sea had a much lower PCB concentration (about 0.2 mg/kg of wet weight). No PCBs and no chlorinated pesticides were found in analyses of the mud at the catching site. High PCB concentrations (3 mg/kg of wet weight) were, however, observed in livers from cod living in the  Gullmar Fjord, and it was proposed that bony fish may be the source of hagfish liver PCBs. PCB chromatograms of hagfish livers differed from those of PCB standards and cod liver. This strange pattern, which was not seen in livers from hagfish caught in the open sea, might be explained by an unusual mode of metabolization. The assays for aflatoxins gave completely negative results.", "contents": "Hepatomas and other neoplasms in the atlantic hagfish (Myxine glutinosa): a histopathologic and chemical study. M. glutinosa is a cyclostome, living in the mud in seawater of high salinity. It probably is a stationary scavenger feeder. About 28,000 hagfish from the Gullmar Fjord were examined during a 5-year period for the occurrence of tumors. Hepatomas were found to be predominant neoplasm, observed at a frequency that decreased from 5.8% in 1972 to 2.9% in 1973 and finally to 0.6% in 1974--76. Islet cell hamartomas and frank neoplasms decreased from 0.5% in 1972 to less than 0.1% in 1973--76. Occasional subcutaneous and mesenterial neoplasms were also observed during 1972--74. In hagfish caught 12 km out in the open sea, the hepatoma incidence decreased from 2.8% in 1972 to 0.9% in 1974. Given this background, it is possible that pollution of the Gullmar Fjord by carcinogenic substances with low biodegradability has occurred until 1972, and this pollution could be of etiologic significance for these hagfish tumors. In fact, the use of PCBs became prohibited by law in Sweden in 1971--72. Severe restrictions were also introduced for the use of chlorinated pesticides, notably DDT, and associated substances (DDD, DDE). Preliminary analyses for the presence of PCBs, DDT (and its metabolites), and aflatoxins (the notorious hepatocarcinogen) were performed by gas chromatography and thin-layer chromatography. Livers (with and without neoplasms) from hagfish caught inside the threshold of the fjord contained about 5 mg/kg of wet weight of PCBs and about 0.1--0.4 mg/kg of dry weight of DDT, DDD, or DDE, whereas those from hagfish caught in the open sea had a much lower PCB concentration (about 0.2 mg/kg of wet weight). No PCBs and no chlorinated pesticides were found in analyses of the mud at the catching site. High PCB concentrations (3 mg/kg of wet weight) were, however, observed in livers from cod living in the  Gullmar Fjord, and it was proposed that bony fish may be the source of hagfish liver PCBs. PCB chromatograms of hagfish livers differed from those of PCB standards and cod liver. This strange pattern, which was not seen in livers from hagfish caught in the open sea, might be explained by an unusual mode of metabolization. The assays for aflatoxins gave completely negative results."}
{"id": "PMID:213000", "title": "A survey of the hormonal factors that control calcium metabolism.", "content": "(1) Vitamin D is the precursor of an extremely potent calcium regulating hormone, 1,25(OH)2D3, which is secreted by the kidney. (2) The secretion of 1,25(OH)2D3 by the kidney is influenced by the calcium and phosphorus content of the diet, parathyroid hormone, and 1,25(OH)2D3 itself. (3)Prolactin and growth hormone are importnat regulators of vitamin D metabolism during pregnancy and growth.", "contents": "A survey of the hormonal factors that control calcium metabolism. (1) Vitamin D is the precursor of an extremely potent calcium regulating hormone, 1,25(OH)2D3, which is secreted by the kidney. (2) The secretion of 1,25(OH)2D3 by the kidney is influenced by the calcium and phosphorus content of the diet, parathyroid hormone, and 1,25(OH)2D3 itself. (3)Prolactin and growth hormone are importnat regulators of vitamin D metabolism during pregnancy and growth."}
{"id": "PMID:213005", "title": "[Warts, viruses, cancer (author's transl)].", "content": "The malignant transformation of cutaneous lesions in epidermodysplasia verruciformis (E.V.), which lesions are caused by a human papilloma virus (HPV), can be compared to that experimentally induced by the polyoma virus. Thus, HPV would undergo a lytic, transformant and/or abortive cycle in epidermal cells. In this latter case, it would increase cell DNA synthesis and there would be production of cellular antigens coded by the virus. This production of cellular antigens would be the result of the incorporation of part of HPV-DNA into the genome of the cell. The presence of part of HPV-DNA in the cell genome would also increase the susceptibility of infected cells to malignant transformation with other Papova viruses. On practical grounds it is not advisable to use potentially mutagenic treatments such as X or U. V. irradiations in the management of HPV induced lesions in man, especially those of E.V.", "contents": "[Warts, viruses, cancer (author's transl)]. The malignant transformation of cutaneous lesions in epidermodysplasia verruciformis (E.V.), which lesions are caused by a human papilloma virus (HPV), can be compared to that experimentally induced by the polyoma virus. Thus, HPV would undergo a lytic, transformant and/or abortive cycle in epidermal cells. In this latter case, it would increase cell DNA synthesis and there would be production of cellular antigens coded by the virus. This production of cellular antigens would be the result of the incorporation of part of HPV-DNA into the genome of the cell. The presence of part of HPV-DNA in the cell genome would also increase the susceptibility of infected cells to malignant transformation with other Papova viruses. On practical grounds it is not advisable to use potentially mutagenic treatments such as X or U. V. irradiations in the management of HPV induced lesions in man, especially those of E.V."}
{"id": "PMID:213007", "title": "[Diarrhea of the newborn animal: nature and mechanism of action of enteropathogenic Escherichia coli in the calf and piglet].", "content": "The present knowledge of the enteropathogenic characteristics of Escherichia coli (adhesion and toxinogenesis) is reviewed in the calf, and compared with piglet data. A pathogenic model of E. coli diarrhoea in the calf is proposed, taking into account the electromyographic, bacteriologic and physiologic data.", "contents": "[Diarrhea of the newborn animal: nature and mechanism of action of enteropathogenic Escherichia coli in the calf and piglet]. The present knowledge of the enteropathogenic characteristics of Escherichia coli (adhesion and toxinogenesis) is reviewed in the calf, and compared with piglet data. A pathogenic model of E. coli diarrhoea in the calf is proposed, taking into account the electromyographic, bacteriologic and physiologic data."}
{"id": "PMID:213008", "title": "Results of an epidemiological investigation on viral arteritis in France and some other European and African countries.", "content": "An original microplate seroneutralization technique was developed in order to study the existence of antibodies against equine viral arteritis. The technique involves a high amount of complement, and has allowed to demonstrate antibodies in 18.5% out of 4,037 horses examined. Titers varied not or little during periods as long as 6 years. Among 3,324 sera samples from French horses, a 15.2% frequency of antibodies was shown. The infection level was not very different between breeds, which is different from results obtained in the U.S.A. with another technique. The infection level increased regularly from 1 to 20 years of age, but, for a constant age, the percentage decreased with the year of birth, between 1950 and 1970. Eight individual infection cases have been identified between 1966 and 1974. It seems that more often the disease occurs without clinical symptoms, or sometimes manifests itself through sporadic abortion. Serological marks of infection have been found at variable levels in all the countries of Europe and Africa investigated. In Africa, a higher level (37.1% among 468 sera) was observed.", "contents": "Results of an epidemiological investigation on viral arteritis in France and some other European and African countries. An original microplate seroneutralization technique was developed in order to study the existence of antibodies against equine viral arteritis. The technique involves a high amount of complement, and has allowed to demonstrate antibodies in 18.5% out of 4,037 horses examined. Titers varied not or little during periods as long as 6 years. Among 3,324 sera samples from French horses, a 15.2% frequency of antibodies was shown. The infection level was not very different between breeds, which is different from results obtained in the U.S.A. with another technique. The infection level increased regularly from 1 to 20 years of age, but, for a constant age, the percentage decreased with the year of birth, between 1950 and 1970. Eight individual infection cases have been identified between 1966 and 1974. It seems that more often the disease occurs without clinical symptoms, or sometimes manifests itself through sporadic abortion. Serological marks of infection have been found at variable levels in all the countries of Europe and Africa investigated. In Africa, a higher level (37.1% among 468 sera) was observed."}
{"id": "PMID:213009", "title": "Human platelet aggregation and cAMP system--cAMP level, adenyl cyclase, phosphodiesterase.", "content": "The possibility of a direct and casual relationship between various parameters of the adenosine 3',5'-cyclic monophosphate (cAMP) system, e.g., the level of cAMP, adenyl cyclase activity and phosphodiesterase activity, and platelet aggregation was studied by measuring the effects of various environmental conditions, as well as metabolic inhibitors, aggregating agents and aggregation inhibitors upon these parameters. A competitive binding technique using 3H labeled cAMP was used to determine the level of cAMP in intact platelets, and a high performance liquid chromatographic method was developed to measure the adenyl cyclase and phosphodiesterase activities in the platelet membrane fraction. Although the availability of substrate adenosine triphosphate (ATP) correlated well with the amount of cAMP produced, and in turn the availability of cAMP seemed to have a direct effect upon the reversibility of shape changes induced by the various stimuli, the only effect upon aggregation concerned the extent to which it occurred. No direct correlation of the level of cAMP with either the actual inhibition or activation of the aggregation mechanism was observed.", "contents": "Human platelet aggregation and cAMP system--cAMP level, adenyl cyclase, phosphodiesterase. The possibility of a direct and casual relationship between various parameters of the adenosine 3',5'-cyclic monophosphate (cAMP) system, e.g., the level of cAMP, adenyl cyclase activity and phosphodiesterase activity, and platelet aggregation was studied by measuring the effects of various environmental conditions, as well as metabolic inhibitors, aggregating agents and aggregation inhibitors upon these parameters. A competitive binding technique using 3H labeled cAMP was used to determine the level of cAMP in intact platelets, and a high performance liquid chromatographic method was developed to measure the adenyl cyclase and phosphodiesterase activities in the platelet membrane fraction. Although the availability of substrate adenosine triphosphate (ATP) correlated well with the amount of cAMP produced, and in turn the availability of cAMP seemed to have a direct effect upon the reversibility of shape changes induced by the various stimuli, the only effect upon aggregation concerned the extent to which it occurred. No direct correlation of the level of cAMP with either the actual inhibition or activation of the aggregation mechanism was observed."}
{"id": "PMID:213014", "title": "Phosphonoacetic acid in the treatment of simian varicella.", "content": "Phosphonoacetic acid inhibited replication of simian varicella virus (Delta herpesvirus) in tissue culture. The drug was tested in patas monkeys 40 h after infection with Delta herpesvirus. A total of 200 mg/kg per day was given intramuscularly, divided into two doses every day for a total of 10 days. The treated monkeys were protected from clinical illness, and Delta herpesvirus was not recovered from their lymphocytes. Complement-fixing and neutralizing antibody titers were significantly lower in phosphonoacetic acid-treated monkeys than in the untreated controls. In animals given the drug alone, there was dermatitis and blackening of the skin and hair, serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase enzymes were significantly increased, and liver biopsy revealed diffuse cytoplasmic swelling and granulation of the hepatocytes. The therapeutic range of this drug should be studied carefully before considering its use in severe varicella-zoster infection in humans.", "contents": "Phosphonoacetic acid in the treatment of simian varicella. Phosphonoacetic acid inhibited replication of simian varicella virus (Delta herpesvirus) in tissue culture. The drug was tested in patas monkeys 40 h after infection with Delta herpesvirus. A total of 200 mg/kg per day was given intramuscularly, divided into two doses every day for a total of 10 days. The treated monkeys were protected from clinical illness, and Delta herpesvirus was not recovered from their lymphocytes. Complement-fixing and neutralizing antibody titers were significantly lower in phosphonoacetic acid-treated monkeys than in the untreated controls. In animals given the drug alone, there was dermatitis and blackening of the skin and hair, serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase enzymes were significantly increased, and liver biopsy revealed diffuse cytoplasmic swelling and granulation of the hepatocytes. The therapeutic range of this drug should be studied carefully before considering its use in severe varicella-zoster infection in humans."}
{"id": "PMID:213010", "title": "MIF-like activity in non-stimulated and virus infected cell cultures.", "content": "Macrophage-migration inhibition factor (MIF) is a lymphocyte-derived substance which plays an important role in cell mediated immunity. Soluble factors containing MIF-like activity and produced by non-stimulated and virus-infected non-lymphoid cell cultures have also been reported. In the present study, a MIF-like factor was repeatedly detected in Buffalo green monkey kidney cells infected with mumps and herpes simplex virus type 1 (HSV-1) indicating that this substance is reproducible and can be stimulated by two viruses of widely varying groups. Wistar-38 (WI-38) cell cultures also increased production of this substance in response to mumps but not HSV-1 infection, indicating that the production of this factor is not necessarily induced by all viruses. A factor which stimulated the spread of macrophages was also found to be induced in WI-38 cells by both viruses, suggesting yet another substance produced by non-lymphoid cells in response to viral infection. The ability of non-stimulated WI-38 cells to produce MIF-like activity was also confirmed, and this factor could be further stimulated or opposed by viral infection.", "contents": "MIF-like activity in non-stimulated and virus infected cell cultures. Macrophage-migration inhibition factor (MIF) is a lymphocyte-derived substance which plays an important role in cell mediated immunity. Soluble factors containing MIF-like activity and produced by non-stimulated and virus-infected non-lymphoid cell cultures have also been reported. In the present study, a MIF-like factor was repeatedly detected in Buffalo green monkey kidney cells infected with mumps and herpes simplex virus type 1 (HSV-1) indicating that this substance is reproducible and can be stimulated by two viruses of widely varying groups. Wistar-38 (WI-38) cell cultures also increased production of this substance in response to mumps but not HSV-1 infection, indicating that the production of this factor is not necessarily induced by all viruses. A factor which stimulated the spread of macrophages was also found to be induced in WI-38 cells by both viruses, suggesting yet another substance produced by non-lymphoid cells in response to viral infection. The ability of non-stimulated WI-38 cells to produce MIF-like activity was also confirmed, and this factor could be further stimulated or opposed by viral infection."}
{"id": "PMID:213015", "title": "Therapeutic effect of trisodium phosphonoformate on cutaneous herpesvirus infection in guinea pigs.", "content": "When applied topically, trisodium phosphonoformate (PFA) displayed activity against established cutaneous herpesvirus infections in guinea pigs similar to that exhibited by the closely related phosphonoacetic acid (PAA); however, unlike PAA, PFA was not locally skin irritating. The therapeutic benefits of topical application of PFA were clearly evident when application was delayed for 48 h after virus inoculation, at which time lesions were well developed. The therapeutic effect was dependent on the concentration of PFA and the duration of treatment. PFA exhibited significant activity against established infections when administered intraperitoneally, although it was less effective via this systemic route than when applied topically.", "contents": "Therapeutic effect of trisodium phosphonoformate on cutaneous herpesvirus infection in guinea pigs. When applied topically, trisodium phosphonoformate (PFA) displayed activity against established cutaneous herpesvirus infections in guinea pigs similar to that exhibited by the closely related phosphonoacetic acid (PAA); however, unlike PAA, PFA was not locally skin irritating. The therapeutic benefits of topical application of PFA were clearly evident when application was delayed for 48 h after virus inoculation, at which time lesions were well developed. The therapeutic effect was dependent on the concentration of PFA and the duration of treatment. PFA exhibited significant activity against established infections when administered intraperitoneally, although it was less effective via this systemic route than when applied topically."}
{"id": "PMID:213016", "title": "HEp-2 cell- and herpes simplex virus type 1- induced deoxythymidine kinases: inhibition by derivatives of 5-trifluoromethyl-2'-deoxyuridine.", "content": "5-Trifluoromethyl-2'-deoxyuridine (F(3)Thd), its free base and nucleotide triphosphate derivative, along with the nucleotide monophosphate and nucleotide triphosphate of deoxythymidine (dThd), were investigated as inhibitors of HEp-2 cell deoxythymidine kinase (dTK) and herpes simplex virus type 1 (HSV-1)-induced dTK. 5-Trifluoromethyluracil did not inhibit cellular or viral dTK. F(3)dThd competitively inhibited phosphorylation of dThd by both the HEp-2 cell- and the HSV-1-induced dTK. The K(mapp) for dThd and the K(Iapp) for the alternate substrate, F(3)dThd, were 3.5 and 22.5 muM for the HEp-2 cell dTK and 63.5 and 71.0 muM for the HSV-1-induced dTK. dThd-5'-PPP at 10 muM inhibited HEp-2 cell- and HSV-1-induced dTK by 94 and 22%, respectively. In comparison, 10 muM F(3)dThD-5'-PPP inhibited HEp-2 cell- and HSV-1-induced dTK 95 and 15%, respectively. These data indicate that F(3)dThd-5'-PPP may mimic dThd-5'-PPP feedback regulation of cellular and viral dTK.", "contents": "HEp-2 cell- and herpes simplex virus type 1- induced deoxythymidine kinases: inhibition by derivatives of 5-trifluoromethyl-2'-deoxyuridine. 5-Trifluoromethyl-2'-deoxyuridine (F(3)Thd), its free base and nucleotide triphosphate derivative, along with the nucleotide monophosphate and nucleotide triphosphate of deoxythymidine (dThd), were investigated as inhibitors of HEp-2 cell deoxythymidine kinase (dTK) and herpes simplex virus type 1 (HSV-1)-induced dTK. 5-Trifluoromethyluracil did not inhibit cellular or viral dTK. F(3)dThd competitively inhibited phosphorylation of dThd by both the HEp-2 cell- and the HSV-1-induced dTK. The K(mapp) for dThd and the K(Iapp) for the alternate substrate, F(3)dThd, were 3.5 and 22.5 muM for the HEp-2 cell dTK and 63.5 and 71.0 muM for the HSV-1-induced dTK. dThd-5'-PPP at 10 muM inhibited HEp-2 cell- and HSV-1-induced dTK by 94 and 22%, respectively. In comparison, 10 muM F(3)dThD-5'-PPP inhibited HEp-2 cell- and HSV-1-induced dTK 95 and 15%, respectively. These data indicate that F(3)dThd-5'-PPP may mimic dThd-5'-PPP feedback regulation of cellular and viral dTK."}
{"id": "PMID:213017", "title": "Resistance of spheroplasts and whole cells of Pseudomonas cepacia to polymyxin B.", "content": "Sucrose-lysozyme spheroplasts were prepared from two strains of Pseudomonas cepacia and tested for susceptibility to polymyxin B and benzalkonium chloride. Spheroplasts were more susceptible than whole cells to benzalkonium chloride but not to polymyxin B. Disruption of the outer membrane layer was not by itself sufficient to render P. cepacia susceptible to polymyxin B.", "contents": "Resistance of spheroplasts and whole cells of Pseudomonas cepacia to polymyxin B. Sucrose-lysozyme spheroplasts were prepared from two strains of Pseudomonas cepacia and tested for susceptibility to polymyxin B and benzalkonium chloride. Spheroplasts were more susceptible than whole cells to benzalkonium chloride but not to polymyxin B. Disruption of the outer membrane layer was not by itself sufficient to render P. cepacia susceptible to polymyxin B."}
{"id": "PMID:213019", "title": "New medium for rapid screening and enumeration of Clostridium perfringens in foods.", "content": "A rapid and sensitive procedure for estimating low numbers of Clostridium perfringens has been investigated and compared to methods used currently in the food industry. The new liquid medium, RPM (rapid perfringens medium), was compared with sulfite-polymyxin-sulfadiazine agar and tryptose-sulfite-cycloserine agar in recovery studies with naturally contaminated and with inoculated foods. The medium consists of a mixture of litmus milk and fluid thioglycolate medium fortified with glucose, peptone, gelatin, yeast extract, sodium chloride, and ferrous sulfate. Selectivity is based on an antibiotic system (polymyxin B sulfate and neomycin sulfate) incorporated into the medium, coupled with an incubation temprature of 46 to 48 degrees C for 24 h. Tubes were scored as positive if a stormy fermentation was observed. All tubes demonstrating stormy fermentation were confirmed as containing C. perfringens. Of a total of 774 naturally contaminated food samples, 546 samples (71%) were found to contain C. perfringens with RPM, whereas only 168 (22%) of the samples were positive using sulfite-polymyxin-sulfadiazine agar. C. perfringens was isolated from 71% of 85 other samples using RPM as compared to 14% with tryptose-sulfite-cycloserine agar. Enumeration studies on 14 individual samples using the most probable number technique also demonstrated greater sensitivity with RPM.", "contents": "New medium for rapid screening and enumeration of Clostridium perfringens in foods. A rapid and sensitive procedure for estimating low numbers of Clostridium perfringens has been investigated and compared to methods used currently in the food industry. The new liquid medium, RPM (rapid perfringens medium), was compared with sulfite-polymyxin-sulfadiazine agar and tryptose-sulfite-cycloserine agar in recovery studies with naturally contaminated and with inoculated foods. The medium consists of a mixture of litmus milk and fluid thioglycolate medium fortified with glucose, peptone, gelatin, yeast extract, sodium chloride, and ferrous sulfate. Selectivity is based on an antibiotic system (polymyxin B sulfate and neomycin sulfate) incorporated into the medium, coupled with an incubation temprature of 46 to 48 degrees C for 24 h. Tubes were scored as positive if a stormy fermentation was observed. All tubes demonstrating stormy fermentation were confirmed as containing C. perfringens. Of a total of 774 naturally contaminated food samples, 546 samples (71%) were found to contain C. perfringens with RPM, whereas only 168 (22%) of the samples were positive using sulfite-polymyxin-sulfadiazine agar. C. perfringens was isolated from 71% of 85 other samples using RPM as compared to 14% with tryptose-sulfite-cycloserine agar. Enumeration studies on 14 individual samples using the most probable number technique also demonstrated greater sensitivity with RPM."}
{"id": "PMID:213018", "title": "Adverse effects of electrical energy applied to the nervous system.", "content": "Neural prostheses activated by radiofrequency transmission are currently being implanted to treat a variety of clinical problems. It is essential that neither the materials used in these prostheses, particularly the electrodes, nor the stimulus parameters that are employed will cause neural damage. The experiences of investigators engaged in both the experimental laboratory and clinical studies of the effects of electrical stimulation are reported herein.", "contents": "Adverse effects of electrical energy applied to the nervous system. Neural prostheses activated by radiofrequency transmission are currently being implanted to treat a variety of clinical problems. It is essential that neither the materials used in these prostheses, particularly the electrodes, nor the stimulus parameters that are employed will cause neural damage. The experiences of investigators engaged in both the experimental laboratory and clinical studies of the effects of electrical stimulation are reported herein."}
{"id": "PMID:213036", "title": "Effect of thyroid hormone, actinomycin D, cycloheximide and puromycin on TRH-induced secretion of TSH, as studied by pituitary concentration of cyclic AMP and intrathyroidal colloid droplet formation.", "content": "In an attempt to study the functional relation between pituitary cyclic AMP and TSH secretion in response to thyrotropin releasing hormone (TRH) or thyroid hormone administration, pituitary concentration of cyclic AMP was measured by protein binding assay after in vivo and in vitro administration of test materials (TRH, thyroxine, triiodothyronine, actinomycin D, puromycin and cycloheximide singly or in combination). Small dose of TRH apparently augmented TSH secretion as evidenced by a marked increase of intrathyroidal colloid droplet, but failed to elevate the pituitary concentration of cyclic AMP. Triiodothyronine (T3) and thyroxine (T4) blocked an increase of TSH secretion produced by TRH, but they elevated pituitary concentration of cyclic AMP in vivo and in vitro. Actinomycin D (Act D), puromycin and cycloheximide elevated pituitary cyclic AMP concentration without stimulating TSH secretion. From the data accumulated, it appears that the measurement of total anterior pituitary concentration of cyclic AMP is not useful to evaluate the activity of TSH cells in response to thyroid hormone, TRH and TRH plus thyroid hormone.", "contents": "Effect of thyroid hormone, actinomycin D, cycloheximide and puromycin on TRH-induced secretion of TSH, as studied by pituitary concentration of cyclic AMP and intrathyroidal colloid droplet formation. In an attempt to study the functional relation between pituitary cyclic AMP and TSH secretion in response to thyrotropin releasing hormone (TRH) or thyroid hormone administration, pituitary concentration of cyclic AMP was measured by protein binding assay after in vivo and in vitro administration of test materials (TRH, thyroxine, triiodothyronine, actinomycin D, puromycin and cycloheximide singly or in combination). Small dose of TRH apparently augmented TSH secretion as evidenced by a marked increase of intrathyroidal colloid droplet, but failed to elevate the pituitary concentration of cyclic AMP. Triiodothyronine (T3) and thyroxine (T4) blocked an increase of TSH secretion produced by TRH, but they elevated pituitary concentration of cyclic AMP in vivo and in vitro. Actinomycin D (Act D), puromycin and cycloheximide elevated pituitary cyclic AMP concentration without stimulating TSH secretion. From the data accumulated, it appears that the measurement of total anterior pituitary concentration of cyclic AMP is not useful to evaluate the activity of TSH cells in response to thyroid hormone, TRH and TRH plus thyroid hormone."}
{"id": "PMID:213037", "title": "The beta-adrenoceptor controlling renin release.", "content": "The beta-adrenoceptor antagonists, atenolol, metoprolol and propranolol, administered intravenously to anaesthetized rats in doses producing equal beta1-adrenoceptor blocking effects, caused comparable suppression of plasma renin activity (PRA) despite the fact that, at these doses, atenolol and metoprolol exhibited no beta2-adrenoceptor blocking properties. Practolol, an agent specific for beta1-adrenoceptors but possessing intrinsic sympathomimetic activity, caused less marked suppression of PRA. When doses of atenolol, metoprolol, propranolol and butoxamine were selected to achieve equal beta2-blocking effects, PRA was again significantly suppressed by atenolol and metoprolol but not by propranolol or butoxamine. These results do not support the concept that adrenergic release of renin is mediated by beta2-adrenoceptors, but are compatible with the involvement of a beta1-adrenoceptor-mediated mechanism.", "contents": "The beta-adrenoceptor controlling renin release. The beta-adrenoceptor antagonists, atenolol, metoprolol and propranolol, administered intravenously to anaesthetized rats in doses producing equal beta1-adrenoceptor blocking effects, caused comparable suppression of plasma renin activity (PRA) despite the fact that, at these doses, atenolol and metoprolol exhibited no beta2-adrenoceptor blocking properties. Practolol, an agent specific for beta1-adrenoceptors but possessing intrinsic sympathomimetic activity, caused less marked suppression of PRA. When doses of atenolol, metoprolol, propranolol and butoxamine were selected to achieve equal beta2-blocking effects, PRA was again significantly suppressed by atenolol and metoprolol but not by propranolol or butoxamine. These results do not support the concept that adrenergic release of renin is mediated by beta2-adrenoceptors, but are compatible with the involvement of a beta1-adrenoceptor-mediated mechanism."}
{"id": "PMID:213034", "title": "[Hormonal regulation of duodeno-pancreatic activity].", "content": "After examining the nature and action of the principal gastroduodenal hormones, the most recent findings regarding hormonal regulation mechanisms of duodeno-pancreatic activity are presented, stress being laid on the close interdependence of the various hormones taking part in the complex digestive event. The role of hormone mediators is then examined with special attention to the action of cyclic AMP and prostaglandine.", "contents": "[Hormonal regulation of duodeno-pancreatic activity]. After examining the nature and action of the principal gastroduodenal hormones, the most recent findings regarding hormonal regulation mechanisms of duodeno-pancreatic activity are presented, stress being laid on the close interdependence of the various hormones taking part in the complex digestive event. The role of hormone mediators is then examined with special attention to the action of cyclic AMP and prostaglandine."}
{"id": "PMID:213040", "title": "Cytomegalovirus-induced thrombocytopenia. An unusual case report.", "content": "A 21-year-old man had severe thrombocytopenia resistant to corticosteroid therapy. Viral studies of cytomegalovirus were 1:1,024. Although the cytomegalovirus titer returned toward normal (1:16 titer) during a period of three months, thrombocytopenia persisted and continued to remain refractory to corticosteroid therapy. Initial bone marrow morphology, platelet size, and platelet survival and sequestration were not typical of idiopathic thrombocytopenic purpura, and it is doubtful that splenectomy would have been helpful. However, when restudied six months later, platelet size was greatly increased, platelet survival was severely shortened (half-time, 2 1/4 hours), and intense splenic trapping was evident. Splenectomy was performed and resulted in normalization of the platelet count. Cytomegalovirus-associated thrombocytopenic purpura is an unusual disease that may take an unpredictable clinical course. Careful study of the mechanism of thrombocytopenia appears worthwhile when early recovery does not occur.", "contents": "Cytomegalovirus-induced thrombocytopenia. An unusual case report. A 21-year-old man had severe thrombocytopenia resistant to corticosteroid therapy. Viral studies of cytomegalovirus were 1:1,024. Although the cytomegalovirus titer returned toward normal (1:16 titer) during a period of three months, thrombocytopenia persisted and continued to remain refractory to corticosteroid therapy. Initial bone marrow morphology, platelet size, and platelet survival and sequestration were not typical of idiopathic thrombocytopenic purpura, and it is doubtful that splenectomy would have been helpful. However, when restudied six months later, platelet size was greatly increased, platelet survival was severely shortened (half-time, 2 1/4 hours), and intense splenic trapping was evident. Splenectomy was performed and resulted in normalization of the platelet count. Cytomegalovirus-associated thrombocytopenic purpura is an unusual disease that may take an unpredictable clinical course. Careful study of the mechanism of thrombocytopenia appears worthwhile when early recovery does not occur."}
{"id": "PMID:213043", "title": "A longitudinal study of the serological and virological status of 18 women infected with cytomegalovirus.", "content": "18 women, of known seropositivity, have been followed for between 18 and 66 months (mean 50.2 months) for viral excretion and serological changes. CMV was isolated from 58/146 (39.7 per cent) cultures from various sites, mostly cervix. A total of 129 sera were obtained and each was titrated in the late antigen, early antigen and anti-complement immunofluorescence assays, as well as the complement fixation and microneutralisation tests. From 3 women virus was consistently re-isolated, from 3 others virus was never re-isolated and the remaining 12 women excreted virus intermittently during the period of study. No significant changes in antibody titres could be detected by any of the 5 serological assays in any woman during periods of viral excretion. This suggests that local reactivation of latent CMV infection is not associated with a demonstrable systemic antibody response. Inter-assay correlations were sought for each of the 10 possible combinations of pairs of tests. Significant correlations were found for most pairs of tests, with the notable exception fo those involving the early antigen test. This confirms that antibodies detected in this assay are distinct from those detected by the other 4 serological assays.", "contents": "A longitudinal study of the serological and virological status of 18 women infected with cytomegalovirus. 18 women, of known seropositivity, have been followed for between 18 and 66 months (mean 50.2 months) for viral excretion and serological changes. CMV was isolated from 58/146 (39.7 per cent) cultures from various sites, mostly cervix. A total of 129 sera were obtained and each was titrated in the late antigen, early antigen and anti-complement immunofluorescence assays, as well as the complement fixation and microneutralisation tests. From 3 women virus was consistently re-isolated, from 3 others virus was never re-isolated and the remaining 12 women excreted virus intermittently during the period of study. No significant changes in antibody titres could be detected by any of the 5 serological assays in any woman during periods of viral excretion. This suggests that local reactivation of latent CMV infection is not associated with a demonstrable systemic antibody response. Inter-assay correlations were sought for each of the 10 possible combinations of pairs of tests. Significant correlations were found for most pairs of tests, with the notable exception fo those involving the early antigen test. This confirms that antibodies detected in this assay are distinct from those detected by the other 4 serological assays."}
{"id": "PMID:213044", "title": "Recovery of a Sendai virus variant with temperature-sensitive hemolytic activity from persistently infected cells from mouse brain.", "content": "A persistently infected cell line designated MB/Senas was established by cultivation of mouse brain cells from four-day-old C3H mice infected intracerebrally at birth with 10(6) PFU of Sendai virus, strain 52. After 5 passages, 0.16 per cent of Sendai52 antiserum (containing two 50 per cent plaque reducing doses/ml of serum) was introduced into the culture medium. The addition of antiserum was accompanied by a rise in cell-associated viral antigen from a level of 5 per cent antigen positive cells to 100 per cent demonstrable by both intracellular and membrane immunofluorescence. A variant of Sendai52 virus, designated Sendaias, was recovered from MB/Senas by inoculation of supernatant medium into chick embryos. Infection of chick embryos at 37 degrees C was abortive. Fifty per cent or less of chick embryos infected at dilutions 10(-1) to 10(-9) yielded detectable virus. Hemagglutination (HA) was weak but could be improved by trypsinization of allantoic fluids. Neuraminidase (NA) activity was barely detectable. Hemolysis (HE) was absent. Propagation of Sendaias virus at 33 degrees C showed no change from weak HA and NA activities but HE activity was now apparent which was temperature sensitive. Mortality of infected chick embryos increased to 100 per cent. HE activity and lethality for chick embryos was thermolabile at 45 degrees C.", "contents": "Recovery of a Sendai virus variant with temperature-sensitive hemolytic activity from persistently infected cells from mouse brain. A persistently infected cell line designated MB/Senas was established by cultivation of mouse brain cells from four-day-old C3H mice infected intracerebrally at birth with 10(6) PFU of Sendai virus, strain 52. After 5 passages, 0.16 per cent of Sendai52 antiserum (containing two 50 per cent plaque reducing doses/ml of serum) was introduced into the culture medium. The addition of antiserum was accompanied by a rise in cell-associated viral antigen from a level of 5 per cent antigen positive cells to 100 per cent demonstrable by both intracellular and membrane immunofluorescence. A variant of Sendai52 virus, designated Sendaias, was recovered from MB/Senas by inoculation of supernatant medium into chick embryos. Infection of chick embryos at 37 degrees C was abortive. Fifty per cent or less of chick embryos infected at dilutions 10(-1) to 10(-9) yielded detectable virus. Hemagglutination (HA) was weak but could be improved by trypsinization of allantoic fluids. Neuraminidase (NA) activity was barely detectable. Hemolysis (HE) was absent. Propagation of Sendaias virus at 33 degrees C showed no change from weak HA and NA activities but HE activity was now apparent which was temperature sensitive. Mortality of infected chick embryos increased to 100 per cent. HE activity and lethality for chick embryos was thermolabile at 45 degrees C."}
{"id": "PMID:213046", "title": "Widespread occurrence in Australian marsupials of neutralizing antibodies to a herpesvirus from a parma wallaby.", "content": "Serum neutralizing antibodies to a parma wallaby herpesvirus (PWHV) have been detected in a wide range of marsupials from different locations across Australia, including several islands. A study of 242 animals (mostly macropods) sampled in the wild showed that 23% had antibodies; a significantly higher frequency (41%) of 116 animals in captivity had antibodies, which were generally at higher levels than those of animals in the wild. Antibodies to PWHV were also detected among parma wallabies from a colony on Kawau Island, New Zealand. The highest antibody levels were found in a group of captive tammar wallabies during recurrent outbreaks of clinical infection. It is suggested that PWHV has evolved along with a marsupial host, and that the high antibody levels among captive animals reflects ease of virus transmission due to crowding, or to conditions of stress leading to expression of latent virus.", "contents": "Widespread occurrence in Australian marsupials of neutralizing antibodies to a herpesvirus from a parma wallaby. Serum neutralizing antibodies to a parma wallaby herpesvirus (PWHV) have been detected in a wide range of marsupials from different locations across Australia, including several islands. A study of 242 animals (mostly macropods) sampled in the wild showed that 23% had antibodies; a significantly higher frequency (41%) of 116 animals in captivity had antibodies, which were generally at higher levels than those of animals in the wild. Antibodies to PWHV were also detected among parma wallabies from a colony on Kawau Island, New Zealand. The highest antibody levels were found in a group of captive tammar wallabies during recurrent outbreaks of clinical infection. It is suggested that PWHV has evolved along with a marsupial host, and that the high antibody levels among captive animals reflects ease of virus transmission due to crowding, or to conditions of stress leading to expression of latent virus."}
{"id": "PMID:213047", "title": "Interaction between infectious bursal disease virus and Newcastle disease virus in chickens.", "content": "The Australian strain of infectious bursal disease virus (IBDV), 002/73, affected the response of chickens to Newcastle disease virus (NDV). The titre of serum antibodies to NDV in chickens infected with IBDV was significantly lower than that of birds infected with NDV alone. It also appeared that IBDV affected NDV excretion from chickens as NDV was more frequently isolated from chickens infected with IBDV, IBDV infection did not alter the pathogenicity of NDV in chickens. This Australian strain of IBDV therefore appeared to be immunodepressive in one-day-old chickens.", "contents": "Interaction between infectious bursal disease virus and Newcastle disease virus in chickens. The Australian strain of infectious bursal disease virus (IBDV), 002/73, affected the response of chickens to Newcastle disease virus (NDV). The titre of serum antibodies to NDV in chickens infected with IBDV was significantly lower than that of birds infected with NDV alone. It also appeared that IBDV affected NDV excretion from chickens as NDV was more frequently isolated from chickens infected with IBDV, IBDV infection did not alter the pathogenicity of NDV in chickens. This Australian strain of IBDV therefore appeared to be immunodepressive in one-day-old chickens."}
{"id": "PMID:213049", "title": "A general method for purification of deoxycytidine kinase.", "content": "Deoxycytidine kinase from a variety of animal tissues binds to Cibacron Blue 3G-A coupled to Sepharose CL-6B. The enzyme can be selectively eluted with ATP to yield single-step purifications of 17-89-fold. The affinity adsorbent is re-usable.", "contents": "A general method for purification of deoxycytidine kinase. Deoxycytidine kinase from a variety of animal tissues binds to Cibacron Blue 3G-A coupled to Sepharose CL-6B. The enzyme can be selectively eluted with ATP to yield single-step purifications of 17-89-fold. The affinity adsorbent is re-usable."}
{"id": "PMID:213050", "title": "Isolation of human lactate dehydrogenase isoenzyme X by affinity chromatography.", "content": "Human isoenzyme LDH-X (lactate dehydrogenase isoenzyme X) was isolated from seminal fluid of frozen semen samples by affinity chromatography by using oxamate-Sepharose and AMP-Sepharose. In the presence of 1.6 mM-NAD+, isoenzyme LDH-X does not bind to AMP-Sepharose, whereas the other lactate dehydrogenase isoenzymes do. This is the crucial point in the isolation of isoenzyme LDH-X from the other isoenzymes. The purified human isoenzyme LDH-X had a specific activity of 146 units/mg of protein.", "contents": "Isolation of human lactate dehydrogenase isoenzyme X by affinity chromatography. Human isoenzyme LDH-X (lactate dehydrogenase isoenzyme X) was isolated from seminal fluid of frozen semen samples by affinity chromatography by using oxamate-Sepharose and AMP-Sepharose. In the presence of 1.6 mM-NAD+, isoenzyme LDH-X does not bind to AMP-Sepharose, whereas the other lactate dehydrogenase isoenzymes do. This is the crucial point in the isolation of isoenzyme LDH-X from the other isoenzymes. The purified human isoenzyme LDH-X had a specific activity of 146 units/mg of protein."}
{"id": "PMID:213051", "title": "Rapid purification and properties of potassium-activated aldehyde dehydrogenase from Saccharomyces cerevisiae.", "content": "A method for the purification of yeast K+-activated aldehyde dehydrogenase is presented which can be completed in substantially less time than other published procedures. The enzyme has a different N-terminal amino acid from preparations previously reported, and other small differences in amino acid content. These differences may be the result of differential proteolytic digestion rather than a different protein in vivo. A purification step involves the biospecific adsorption on affinity columns containing immobilized nucleotides in the absence of the substrate aldehyde. Direct binding studies with the coenzyme in the absence of aldehyde reveal 4 NAD sites per tetrameric molecule, each with a dissociation constant of 120 micron. These results conflict with properties of preparations previously reported and may conflict with kinetic models that have aldehyde as the leading substrate. Binding to Blue Dextran affinity columns suggests the presence of a dinucleotide fold in common with other dehydrogenases and kinases.", "contents": "Rapid purification and properties of potassium-activated aldehyde dehydrogenase from Saccharomyces cerevisiae. A method for the purification of yeast K+-activated aldehyde dehydrogenase is presented which can be completed in substantially less time than other published procedures. The enzyme has a different N-terminal amino acid from preparations previously reported, and other small differences in amino acid content. These differences may be the result of differential proteolytic digestion rather than a different protein in vivo. A purification step involves the biospecific adsorption on affinity columns containing immobilized nucleotides in the absence of the substrate aldehyde. Direct binding studies with the coenzyme in the absence of aldehyde reveal 4 NAD sites per tetrameric molecule, each with a dissociation constant of 120 micron. These results conflict with properties of preparations previously reported and may conflict with kinetic models that have aldehyde as the leading substrate. Binding to Blue Dextran affinity columns suggests the presence of a dinucleotide fold in common with other dehydrogenases and kinases."}
{"id": "PMID:213052", "title": "The mechanism of reaction of fully reduced membrane-bound cytochrome oxidase with oxygen at 176K.", "content": "1. The results of non-linear optimization studies on the mechanism of reaction of fully reduced cytochrome oxidase with O2 at 176K are presented. The analysis is carried out on data obtained by means of dual-wavelength multi-channel spectroscopy at three wavelength pairs (604-630, 608-630 and 830-940 nm) and at three O2 concentrations (60, 200 and 1180 micron). The only model that satisfies the triple requirement of a standard deviation within the standard error of the experimental data, good determination of the optimized parameters and a random distribution of residuals is a three-species sequential mechanism. 2. On the basis of the optimized values of the relative absorption coefficients of the intermediates at each wavelength obtained from the present paper together with data from low-temperature trapping, e.p.r. and magnetic-susceptibility studies, the possible valence states of the metal centres in each of the intermediates are discussed.", "contents": "The mechanism of reaction of fully reduced membrane-bound cytochrome oxidase with oxygen at 176K. 1. The results of non-linear optimization studies on the mechanism of reaction of fully reduced cytochrome oxidase with O2 at 176K are presented. The analysis is carried out on data obtained by means of dual-wavelength multi-channel spectroscopy at three wavelength pairs (604-630, 608-630 and 830-940 nm) and at three O2 concentrations (60, 200 and 1180 micron). The only model that satisfies the triple requirement of a standard deviation within the standard error of the experimental data, good determination of the optimized parameters and a random distribution of residuals is a three-species sequential mechanism. 2. On the basis of the optimized values of the relative absorption coefficients of the intermediates at each wavelength obtained from the present paper together with data from low-temperature trapping, e.p.r. and magnetic-susceptibility studies, the possible valence states of the metal centres in each of the intermediates are discussed."}
{"id": "PMID:213053", "title": "The mechanism of reaction of ferricyanide-pretreated mixed-valence-state membrane-bound cytochrome oxidase with oxygen at 173 K.", "content": "1. The results of non-linear optimization studies on the mechanism of reaction of ferricyanide-pretreated mixed-valence-state cytochrome oxidase with O2 at 173 K are presented. The analysis is carried out on data obtained by means of dual-wavelength multi-channel spectroscopy at four wavelength pairs (444-463 nm, 604-630 nm, 608-630 nm and 830-940 nm) and at two O2 concentrations (360 micron and 520 micron). The only model that satisfies the triple requirement of a standard deviation within the standard error of the experimental data, a random distribution of residuals and good determination of the optimized parameters, is a three-intermediate sequential mechanism. 2. On the basis of the optimized values of the relative absorption coefficients of the intermediates at each wavelength obtained from the present paper together with data from optical wavelength scanning and e.p.r. spectroscopy obtained by low-temperature trapping studies, the possible valence states of the metal centres in each of the intermediates are discussed.", "contents": "The mechanism of reaction of ferricyanide-pretreated mixed-valence-state membrane-bound cytochrome oxidase with oxygen at 173 K. 1. The results of non-linear optimization studies on the mechanism of reaction of ferricyanide-pretreated mixed-valence-state cytochrome oxidase with O2 at 173 K are presented. The analysis is carried out on data obtained by means of dual-wavelength multi-channel spectroscopy at four wavelength pairs (444-463 nm, 604-630 nm, 608-630 nm and 830-940 nm) and at two O2 concentrations (360 micron and 520 micron). The only model that satisfies the triple requirement of a standard deviation within the standard error of the experimental data, a random distribution of residuals and good determination of the optimized parameters, is a three-intermediate sequential mechanism. 2. On the basis of the optimized values of the relative absorption coefficients of the intermediates at each wavelength obtained from the present paper together with data from optical wavelength scanning and e.p.r. spectroscopy obtained by low-temperature trapping studies, the possible valence states of the metal centres in each of the intermediates are discussed."}
{"id": "PMID:213054", "title": "Measurement of adenosine 3':5'-cyclic monophosphate by competitive binding to salt-dissociated protein kinase.", "content": "An assay for cyclic AMP is described which takes advantage of the high affinity of the dissociated receptor moiety of cyclic AMP-dependent protein kinase I for the nucleotide. The kinase is kept dissociated by salt (800 mM-NaCl/30mM-EDTA). In the presence of a simply prepared heat-stable protein fraction the binding reagent is stable for the time needed to reach equilibrium of binding. A simple procedure [precipitation with poly-(ethylene glycol) followed by DEAE-cellulose chromatography] is described for the separation of protein kinase I from other binding proteins for cyclic AMP in rabbit skeletal muscle. The sensitivity, precision, reproducibility and specificity of the assay compared favourably with those of other cyclic AMP assays. The main advantage of the present assay is its resistance towards non-specific interference from a number of salts, tissue-culture media and substances found in crude tissue extracts. The reliability of cyclic AMP measurement directly in crude tissue extracts was ensured by removal of the assayable cyclic AMP with cyclic nucleotide phosphodiesterase digestion or adsorption with antibody against cyclic AMP, by comparison with measurement in tissue extracts purified by chromatography on QAE-Sephadex or sequentially on Dowex 50, and aluminium oxide as well as by dilution and recovery experiments.", "contents": "Measurement of adenosine 3':5'-cyclic monophosphate by competitive binding to salt-dissociated protein kinase. An assay for cyclic AMP is described which takes advantage of the high affinity of the dissociated receptor moiety of cyclic AMP-dependent protein kinase I for the nucleotide. The kinase is kept dissociated by salt (800 mM-NaCl/30mM-EDTA). In the presence of a simply prepared heat-stable protein fraction the binding reagent is stable for the time needed to reach equilibrium of binding. A simple procedure [precipitation with poly-(ethylene glycol) followed by DEAE-cellulose chromatography] is described for the separation of protein kinase I from other binding proteins for cyclic AMP in rabbit skeletal muscle. The sensitivity, precision, reproducibility and specificity of the assay compared favourably with those of other cyclic AMP assays. The main advantage of the present assay is its resistance towards non-specific interference from a number of salts, tissue-culture media and substances found in crude tissue extracts. The reliability of cyclic AMP measurement directly in crude tissue extracts was ensured by removal of the assayable cyclic AMP with cyclic nucleotide phosphodiesterase digestion or adsorption with antibody against cyclic AMP, by comparison with measurement in tissue extracts purified by chromatography on QAE-Sephadex or sequentially on Dowex 50, and aluminium oxide as well as by dilution and recovery experiments."}
{"id": "PMID:213055", "title": "The mode of regulation of pyruvate dehydrogenase of lactating rat mammary gland. Effects of starvation and insulin.", "content": "1. The ;initial activity' of the pyruvate dehydrogenase enzyme complex in whole tissue or mitochondrial extracts of lactating rat mammary glands was greatly decreased by 24 or 48h starvation of the rats. Injection of insulin and glucose into starved rats 60min before removal of the glands abolished this difference in ;initial activities'. 2. The ;total activity' of the enzyme complex in such extracts was revealed by incubation in the presence of free Mg(2+) and Ca(2+) ions (more than 10 and 0.1mm respectively) and a crude preparation of pig heart pyruvate dehydrogenase phosphatase. Starvation did not alter this ;total activity'. It is assumed that the decline in ;initial activity' of the enzyme complex derived from the glands of starved animals was due to increased phosphorylation of its alpha-subunit by intrinsic pyruvate dehydrogenase kinase. 3. Starvation led to an increase in intrinsic pyruvate dehydrogenase kinase activity in both whole tissue and mitochondrial extracts. Injection of insulin into starved animals 30min before removal of the lactating mammary glands abolished the increase in pyruvate dehydrogenase kinase activity in whole-tissue extracts. 4. Pyruvate (1mm) prevented ATP-induced inactivation of the enzyme complex in mitochondrial extracts from glands of fed animals. In similar extracts from starved animals pyruvate was ineffective. 5. Starvation led to a decline in activity of pyruvate dehydrogenase phosphatase in mitochondrial extracts, but not in whole-tissue extracts. 6. These changes in activity of the intrinsic kinase and phosphatase of the pyruvate dehydrogenase complex of lactating rat mammary gland are not explicable by current theories of regulation of the complex.", "contents": "The mode of regulation of pyruvate dehydrogenase of lactating rat mammary gland. Effects of starvation and insulin. 1. The ;initial activity' of the pyruvate dehydrogenase enzyme complex in whole tissue or mitochondrial extracts of lactating rat mammary glands was greatly decreased by 24 or 48h starvation of the rats. Injection of insulin and glucose into starved rats 60min before removal of the glands abolished this difference in ;initial activities'. 2. The ;total activity' of the enzyme complex in such extracts was revealed by incubation in the presence of free Mg(2+) and Ca(2+) ions (more than 10 and 0.1mm respectively) and a crude preparation of pig heart pyruvate dehydrogenase phosphatase. Starvation did not alter this ;total activity'. It is assumed that the decline in ;initial activity' of the enzyme complex derived from the glands of starved animals was due to increased phosphorylation of its alpha-subunit by intrinsic pyruvate dehydrogenase kinase. 3. Starvation led to an increase in intrinsic pyruvate dehydrogenase kinase activity in both whole tissue and mitochondrial extracts. Injection of insulin into starved animals 30min before removal of the lactating mammary glands abolished the increase in pyruvate dehydrogenase kinase activity in whole-tissue extracts. 4. Pyruvate (1mm) prevented ATP-induced inactivation of the enzyme complex in mitochondrial extracts from glands of fed animals. In similar extracts from starved animals pyruvate was ineffective. 5. Starvation led to a decline in activity of pyruvate dehydrogenase phosphatase in mitochondrial extracts, but not in whole-tissue extracts. 6. These changes in activity of the intrinsic kinase and phosphatase of the pyruvate dehydrogenase complex of lactating rat mammary gland are not explicable by current theories of regulation of the complex."}
{"id": "PMID:213056", "title": "Phosphorylation of glucose in isolated rat hepatocytes. Sigmoidal kinetics explained by the activity of glucokinase alone.", "content": "The conversion of glucose into glucose 6-phosphate in an extract of isolated rat hepatocytes incubated in the presence of MgATP was studied spectrophotometrically at 340nm and also by a radiochemical procedure based on the release of (3)H from [2-(3)H]glucose. Both methods gave similar results. The glucose-saturation curve was sigmoidal and the shape of this curve was not influenced by the ionic composition of the incubation medium. The activity at 0.5mm-glucose was only 1-2% of V(max.), indicating a virtual absence of low-K(m) hexokinase in the preparation. The radiochemical method was also used for the determination of glucose phosphorylation by intact hepatocytes. The glucose-saturation curve was also markedly sigmoidal, but the s(0.5) (substrate concentration at half-maximal velocity) and the Hill coefficient were larger than in extracts of hepatocytes. These two parameters became smaller when cells were incubated in a medium in which Na(+) ions were replaced by K(+) ions. The increased rate of phosphorylation at low glucose concentration in a K(+) medium was accompanied by an increased rate of metabolite recycling between glucose and glucose 6-phosphate and also by an increased uptake of glucose. In both media phosphorylation of glucose was inhibited co-operatively by N-acetylglucosamine. Calculations indicate that this inhibition would reach 100% at saturation of the inhibitor, although at lower concentrations of N-acetylglucosamine it was smaller than expected from the known K(i) of N-acetylglucosamine for glucokinase. The rate of phosphorylation of glucose was proportional to the amount of glucokinase in hepatocytes from newborn rats and in conditions such as starvation and diabetes in which the total amount of glucokinase in the liver is decreased. In the same conditions, glucose 6-phosphatase activity was either normal or increased. It is concluded that the phosphorylation of glucose in isolated hepatocytes follows sigmoidal kinetics, which can be explained by the activity of glucokinase alone with no participation of low-K(m) hexokinase or of glucose 6-phosphatase.", "contents": "Phosphorylation of glucose in isolated rat hepatocytes. Sigmoidal kinetics explained by the activity of glucokinase alone. The conversion of glucose into glucose 6-phosphate in an extract of isolated rat hepatocytes incubated in the presence of MgATP was studied spectrophotometrically at 340nm and also by a radiochemical procedure based on the release of (3)H from [2-(3)H]glucose. Both methods gave similar results. The glucose-saturation curve was sigmoidal and the shape of this curve was not influenced by the ionic composition of the incubation medium. The activity at 0.5mm-glucose was only 1-2% of V(max.), indicating a virtual absence of low-K(m) hexokinase in the preparation. The radiochemical method was also used for the determination of glucose phosphorylation by intact hepatocytes. The glucose-saturation curve was also markedly sigmoidal, but the s(0.5) (substrate concentration at half-maximal velocity) and the Hill coefficient were larger than in extracts of hepatocytes. These two parameters became smaller when cells were incubated in a medium in which Na(+) ions were replaced by K(+) ions. The increased rate of phosphorylation at low glucose concentration in a K(+) medium was accompanied by an increased rate of metabolite recycling between glucose and glucose 6-phosphate and also by an increased uptake of glucose. In both media phosphorylation of glucose was inhibited co-operatively by N-acetylglucosamine. Calculations indicate that this inhibition would reach 100% at saturation of the inhibitor, although at lower concentrations of N-acetylglucosamine it was smaller than expected from the known K(i) of N-acetylglucosamine for glucokinase. The rate of phosphorylation of glucose was proportional to the amount of glucokinase in hepatocytes from newborn rats and in conditions such as starvation and diabetes in which the total amount of glucokinase in the liver is decreased. In the same conditions, glucose 6-phosphatase activity was either normal or increased. It is concluded that the phosphorylation of glucose in isolated hepatocytes follows sigmoidal kinetics, which can be explained by the activity of glucokinase alone with no participation of low-K(m) hexokinase or of glucose 6-phosphatase."}
{"id": "PMID:213057", "title": "Calcium ion cycling in rat liver mitochondria.", "content": "1. Addition of N-ethylmaleimide to rat liver mitochondria respiring with succinate as substrate decreases both the initial rate of Ca(2+) transport and the ability of mitochondria to retain Ca(2+). As a result, Ca(2+) begins to leave the mitochondria soon after it has entered. Half-maximal effects occur at an N-ethylmaleimide concentration of about 100nmol/mg of protein. 2. The efflux of Ca(2+) induced by N-ethylmaleimide is not prevented by Mg(2+) or by Ruthenium Red at concentrations known to prevent Ca(2+) efflux when exogenous phosphate also is present. Swelling of mitochondria does not accompany N-ethylmaleimide-induced Ca(2+) efflux. 3. Addition of Ca(2+) to rat liver mitochondria in the presence of N-ethylmaleimide produces an immediate decrease in DeltaE (membrane potential), which decreases further to only a slight extent over the next 8min. Concomitant with this is an immediate increase and then levelling off of the -59DeltapH (transmembrane pH gradient). 4. Preincubation of rat liver mitochondria with p-chloromercuribenzenesulphonate, which by contrast with N-ethylmaleimide is unable to penetrate the inner mitochondrial membrane, also prevents Ca(2+) retention. The DeltaE and -59DeltapH respond to Ca(2+) addition in a manner similar to that which occurs when N-ethylmaleimide is present. Subsequent addition of mercaptoethanol produces an immediate increase in both DeltaE and -59DeltapH. At the same time Ca(2+) is rapidly accumulated by the organelles. 5. The above data are interpreted as indicating that under the conditions of Ca(2+) efflux seen here, the mitochondria retain their functional integrity. This contrasts with the uncoupling effect of Ca(2+) seen in the presence of P(i), which generally leads to a loss of mitochondrial integrity. We suggest that a unique mechanism of Ca(2+) cycling is able to take place when mitochondria have been treated with N-ethylmaleimide.", "contents": "Calcium ion cycling in rat liver mitochondria. 1. Addition of N-ethylmaleimide to rat liver mitochondria respiring with succinate as substrate decreases both the initial rate of Ca(2+) transport and the ability of mitochondria to retain Ca(2+). As a result, Ca(2+) begins to leave the mitochondria soon after it has entered. Half-maximal effects occur at an N-ethylmaleimide concentration of about 100nmol/mg of protein. 2. The efflux of Ca(2+) induced by N-ethylmaleimide is not prevented by Mg(2+) or by Ruthenium Red at concentrations known to prevent Ca(2+) efflux when exogenous phosphate also is present. Swelling of mitochondria does not accompany N-ethylmaleimide-induced Ca(2+) efflux. 3. Addition of Ca(2+) to rat liver mitochondria in the presence of N-ethylmaleimide produces an immediate decrease in DeltaE (membrane potential), which decreases further to only a slight extent over the next 8min. Concomitant with this is an immediate increase and then levelling off of the -59DeltapH (transmembrane pH gradient). 4. Preincubation of rat liver mitochondria with p-chloromercuribenzenesulphonate, which by contrast with N-ethylmaleimide is unable to penetrate the inner mitochondrial membrane, also prevents Ca(2+) retention. The DeltaE and -59DeltapH respond to Ca(2+) addition in a manner similar to that which occurs when N-ethylmaleimide is present. Subsequent addition of mercaptoethanol produces an immediate increase in both DeltaE and -59DeltapH. At the same time Ca(2+) is rapidly accumulated by the organelles. 5. The above data are interpreted as indicating that under the conditions of Ca(2+) efflux seen here, the mitochondria retain their functional integrity. This contrasts with the uncoupling effect of Ca(2+) seen in the presence of P(i), which generally leads to a loss of mitochondrial integrity. We suggest that a unique mechanism of Ca(2+) cycling is able to take place when mitochondria have been treated with N-ethylmaleimide."}
{"id": "PMID:213058", "title": "Effect of adrenalectomy on acceleration of gluconeogenesis by calcium ions, adenosine 3':5'-cyclic monophosphate and adrenaline in rat kidney tubules.", "content": "1. Gluconeogenesis from pyruvate was measured in renal-cortical-tubules fragments prepared from fed male rats 6-8 days after adrenalectomy or sham adrenalectomy. The response of this process to 3':5'-cyclic AMP and adrenaline was compared in these two states at two Ca2+ concentrations. 2. Adrenalectomy decreased the percentage stimulation of gluconeogenesis by 3':5'-cyclic AMP, but increased percentage stimulation by adrenaline. Cortisol treatment of adrenalectomized rats (50 mg/kg, twice daily for 2 days) did not reverse the change in responsiveness to 3':5'-cyclic AMP and adrenaline. 3. Stimulation of gluconeogenesis by 1 micron-adrenaline was unaffected by 10 micron-propranolol (beta-blocker) in either state. Phentolamine (alpha-blocker; 10 micron) totally blocked stimulation of gluconeogenesis by 1 micron-adrenaline in the sham-operated condition, but was only partially effective in this respect after adrenalectomy.", "contents": "Effect of adrenalectomy on acceleration of gluconeogenesis by calcium ions, adenosine 3':5'-cyclic monophosphate and adrenaline in rat kidney tubules. 1. Gluconeogenesis from pyruvate was measured in renal-cortical-tubules fragments prepared from fed male rats 6-8 days after adrenalectomy or sham adrenalectomy. The response of this process to 3':5'-cyclic AMP and adrenaline was compared in these two states at two Ca2+ concentrations. 2. Adrenalectomy decreased the percentage stimulation of gluconeogenesis by 3':5'-cyclic AMP, but increased percentage stimulation by adrenaline. Cortisol treatment of adrenalectomized rats (50 mg/kg, twice daily for 2 days) did not reverse the change in responsiveness to 3':5'-cyclic AMP and adrenaline. 3. Stimulation of gluconeogenesis by 1 micron-adrenaline was unaffected by 10 micron-propranolol (beta-blocker) in either state. Phentolamine (alpha-blocker; 10 micron) totally blocked stimulation of gluconeogenesis by 1 micron-adrenaline in the sham-operated condition, but was only partially effective in this respect after adrenalectomy."}
{"id": "PMID:213059", "title": "The involvement of phosphatidate phosphohydrolase and phospholipase A activities in the control of hepatic glycerolipid synthesis. Effects of acute feeding with glucose, fructose, sorbitol, glycerol and ethanol.", "content": "Rats were fed by stomach tube with a single dose of glucose, sorbitol, fructose, glycerol or ethanol of equivalent energy contents or with 0.15 M-NaCl. They were killed 6 h later and the relative rates of phosphatidate deacylation and dephosphorylation measured in the microsomal and supernatant fractions of the livers. Treatment with sorbitol, fructose, glycerol and ethanol increased phosphohydrolase activities in the microsomal and supernatant fractions. The only significant change in deacylase activity was an increase in the microsomal fraction produced by ethanol. It is proposed that hepatic triacylglycerol synthesis is partly controlled by the balance between phosphatidate phosphohydrolase and phospholipase A-type activities.", "contents": "The involvement of phosphatidate phosphohydrolase and phospholipase A activities in the control of hepatic glycerolipid synthesis. Effects of acute feeding with glucose, fructose, sorbitol, glycerol and ethanol. Rats were fed by stomach tube with a single dose of glucose, sorbitol, fructose, glycerol or ethanol of equivalent energy contents or with 0.15 M-NaCl. They were killed 6 h later and the relative rates of phosphatidate deacylation and dephosphorylation measured in the microsomal and supernatant fractions of the livers. Treatment with sorbitol, fructose, glycerol and ethanol increased phosphohydrolase activities in the microsomal and supernatant fractions. The only significant change in deacylase activity was an increase in the microsomal fraction produced by ethanol. It is proposed that hepatic triacylglycerol synthesis is partly controlled by the balance between phosphatidate phosphohydrolase and phospholipase A-type activities."}
{"id": "PMID:213081", "title": "Sitosterol in juvenile type II hyperlipoproteinemia.", "content": "The effect of beta-sitosterol on plasma lipids and lipoproteins was evaluated in a randomized double-blind cross-over trial in 15 children and adolescents with familial hypercholesterolemia over a period of 6 months. Twelve patients completed the study, with good adherence to drug intake. Sitosterol lowered the plasma total choelsterol by 6%, LDL cholesterol by 7% and HDL cholesterol by 15% (P less than 0.05). This insufficient response of total and LDL cholesterol and the marked fall of HDL cholesterol appears to advise against the use of beta-sitosterol granulate in juvenile type II hyperlipoproteinemia.", "contents": "Sitosterol in juvenile type II hyperlipoproteinemia. The effect of beta-sitosterol on plasma lipids and lipoproteins was evaluated in a randomized double-blind cross-over trial in 15 children and adolescents with familial hypercholesterolemia over a period of 6 months. Twelve patients completed the study, with good adherence to drug intake. Sitosterol lowered the plasma total choelsterol by 6%, LDL cholesterol by 7% and HDL cholesterol by 15% (P less than 0.05). This insufficient response of total and LDL cholesterol and the marked fall of HDL cholesterol appears to advise against the use of beta-sitosterol granulate in juvenile type II hyperlipoproteinemia."}
{"id": "PMID:213082", "title": "Hypercholesterolemia in renal allograft recipients. Comparison with non-renal hypercholesterolemia and normal subjects.", "content": "In order to investigate the degree of similarity between renal transplant and non-renal hypercholesterolemia, serum and lipoprotein lipid compositions were compared in female transplant hypercholesterolemic patients (serum cholesterol greater than 240 mg/100 ml, serum triglyceride less than 150 mg/100 ml) and female non-renal hypercholesterolemic and normal subjects. A number of lipid abnormalities were demonstrated: (1) Serum and LDL cholesterol and phospholipid levels were significantly elevated in both transplant and non-renal hypercholesterolemic patients; (2) Serum triglyceride, VLDL choelsterol, triglyceride and phospholipid, and LDL and HDL triglyceride were significantly increased in transplant hypercholesterolemic patients. Changes of this nature are usually found in hypertriglyceridemia, and were not observed in non-renal hypercholesterolemic subjects. Finally, a number of changes in the ratio of esterified to free cholesterol and in the ratios of other lipoprotein-lipids, most of which did not correspond to any changes found in the common non-renal hyperlipidemias, were also demonstrated.", "contents": "Hypercholesterolemia in renal allograft recipients. Comparison with non-renal hypercholesterolemia and normal subjects. In order to investigate the degree of similarity between renal transplant and non-renal hypercholesterolemia, serum and lipoprotein lipid compositions were compared in female transplant hypercholesterolemic patients (serum cholesterol greater than 240 mg/100 ml, serum triglyceride less than 150 mg/100 ml) and female non-renal hypercholesterolemic and normal subjects. A number of lipid abnormalities were demonstrated: (1) Serum and LDL cholesterol and phospholipid levels were significantly elevated in both transplant and non-renal hypercholesterolemic patients; (2) Serum triglyceride, VLDL choelsterol, triglyceride and phospholipid, and LDL and HDL triglyceride were significantly increased in transplant hypercholesterolemic patients. Changes of this nature are usually found in hypertriglyceridemia, and were not observed in non-renal hypercholesterolemic subjects. Finally, a number of changes in the ratio of esterified to free cholesterol and in the ratios of other lipoprotein-lipids, most of which did not correspond to any changes found in the common non-renal hyperlipidemias, were also demonstrated."}
{"id": "PMID:213083", "title": "Relationship between the carbohydrate content of apoproteins of VLDL, IDL, and LDL and the plasma level of these lipoproteins in man. Short dietary effect.", "content": "A 1,500 Cal test meal was used to study in man the apoprotein B-carbohydrate content and composition of VLDL, IDL and LDL in relation to the variation of plasma lipids and lipoproteins and the VLDL-apoprotein composition. Three essential facts emerge from the study: (1) the mirror image (inverse significant correlation) between VLDL-apo B plasma concentration and N-acetylglucosamine content of apo B; (2) a reduction in total carbohydate concentration of VLDL- and LDL-apo B, 2--4 h after the test meal and a trend to a reduction in the mannose content; (3) a significant correlation between sialic acid and apoprotein B concentration in plasma LDL during fasting. The effect of diet and subsequent fasting on carbohydrates of lipoproteins and the consequence of such changes on lipoprotein uptake are briefly discussed.", "contents": "Relationship between the carbohydrate content of apoproteins of VLDL, IDL, and LDL and the plasma level of these lipoproteins in man. Short dietary effect. A 1,500 Cal test meal was used to study in man the apoprotein B-carbohydrate content and composition of VLDL, IDL and LDL in relation to the variation of plasma lipids and lipoproteins and the VLDL-apoprotein composition. Three essential facts emerge from the study: (1) the mirror image (inverse significant correlation) between VLDL-apo B plasma concentration and N-acetylglucosamine content of apo B; (2) a reduction in total carbohydate concentration of VLDL- and LDL-apo B, 2--4 h after the test meal and a trend to a reduction in the mannose content; (3) a significant correlation between sialic acid and apoprotein B concentration in plasma LDL during fasting. The effect of diet and subsequent fasting on carbohydrates of lipoproteins and the consequence of such changes on lipoprotein uptake are briefly discussed."}
{"id": "PMID:213086", "title": "Lipid composition of serum lipoproteins in patients with primary type IIb and type IV hyperlipoproteinemia.", "content": "Cholesterol, triglyceride and phospholipid concentrations of VLDL, LDL and HDL were studied in 20 patients with primary type IIb, 25 patients with primary type IV and in 18 controls. Both types are not only characterized by different concentrations of lipoprotein lipids, but also by their different lipid composition. Type IIb had more triglycerides in the LDL, type IV in the LDL and HDL. The HDL cholesterol content of type IV was decreased. The percent phospholipid concentration of HDL was identical in the 3 groups, demonstrating the constant role of this lipid fraction. The lipid relationships between the lipoproteins showed that the LDL/HDL lipid ratio of type IIb exceeded type IV ratio in spite of normal HDL lipid concentration in type IIb.", "contents": "Lipid composition of serum lipoproteins in patients with primary type IIb and type IV hyperlipoproteinemia. Cholesterol, triglyceride and phospholipid concentrations of VLDL, LDL and HDL were studied in 20 patients with primary type IIb, 25 patients with primary type IV and in 18 controls. Both types are not only characterized by different concentrations of lipoprotein lipids, but also by their different lipid composition. Type IIb had more triglycerides in the LDL, type IV in the LDL and HDL. The HDL cholesterol content of type IV was decreased. The percent phospholipid concentration of HDL was identical in the 3 groups, demonstrating the constant role of this lipid fraction. The lipid relationships between the lipoproteins showed that the LDL/HDL lipid ratio of type IIb exceeded type IV ratio in spite of normal HDL lipid concentration in type IIb."}
{"id": "PMID:213088", "title": "Relative increase in apolipoprotein CII content of VLDL and chylomicrons in a case with massive type V hyperlipoproteinaemia by nicotinic acid treatment.", "content": "VLDL of fasting serum was fractionated into 4 fractions of decreasing particle size by preparative ultracentrifugation in a density gradient from a patient with massive type V hyperlipoproteinaemia before and after treatment with 12 g daily of nicotinic acid. Serum triglycerides fell from 58 to 9 mmol/1 in response to treatment due particularly to reduction of larger VLDL particles. Total, insoluble (apoprotein B) and soluble protein of all VLDL fractions also fell but the ratio of these 3 protein fractions to triglyceride rose particularly in the smaller VLDL fractions. The relative amount of apolipoprotein CII increased in all fractions and the ratio apo CII to triglycerides increased by 60--90% in all VLDL fractions. The relative amounts of apo CI, apo CII-2 and apo E appeared also to increase. The results are consistent with the hypothesis that low amounts of apo CII may play a role for the development of hypertriglyceridaemia.", "contents": "Relative increase in apolipoprotein CII content of VLDL and chylomicrons in a case with massive type V hyperlipoproteinaemia by nicotinic acid treatment. VLDL of fasting serum was fractionated into 4 fractions of decreasing particle size by preparative ultracentrifugation in a density gradient from a patient with massive type V hyperlipoproteinaemia before and after treatment with 12 g daily of nicotinic acid. Serum triglycerides fell from 58 to 9 mmol/1 in response to treatment due particularly to reduction of larger VLDL particles. Total, insoluble (apoprotein B) and soluble protein of all VLDL fractions also fell but the ratio of these 3 protein fractions to triglyceride rose particularly in the smaller VLDL fractions. The relative amount of apolipoprotein CII increased in all fractions and the ratio apo CII to triglycerides increased by 60--90% in all VLDL fractions. The relative amounts of apo CI, apo CII-2 and apo E appeared also to increase. The results are consistent with the hypothesis that low amounts of apo CII may play a role for the development of hypertriglyceridaemia."}
{"id": "PMID:213089", "title": "HDL-cholesterol, apolipoproteins A1 and B. Age and index body weight.", "content": "Some data of previous literature have emphasized a negative correlation between plasma apo A1, HDL cholesterol and coronary heart disease. The present paper stresses a high negative correlation existing both in females and males between values of index body weight (IBW) and plasma levels of HDL cholesterol and apo A1. No correlation has been found between age and, respectively, HDL cholesterol, apo A1 and apo B.", "contents": "HDL-cholesterol, apolipoproteins A1 and B. Age and index body weight. Some data of previous literature have emphasized a negative correlation between plasma apo A1, HDL cholesterol and coronary heart disease. The present paper stresses a high negative correlation existing both in females and males between values of index body weight (IBW) and plasma levels of HDL cholesterol and apo A1. No correlation has been found between age and, respectively, HDL cholesterol, apo A1 and apo B."}
{"id": "PMID:213090", "title": "Further studies on serum lipoproteins in connective tissue diseases.", "content": "Men with ankylosing spondylitis (AS) and females with systemic lupus erythematosus (SLE) were found to have low total serum lipid concentrations similar to results previously obtained in patients with rheumatoid arthritis (RA). In AS men total serum TG was about 50% of control values and in AS men and SLE women total serum cholesterol was 78% of control values but close to corresponding RA concentrations. This was explained mainly by low LDL concentrations. There was a marked difference between RA patients and AS and SLE patients in that the two latter groups had normal HDL cholesterol concentrations whereas in RA patients the HDL cholesterol concentration was only 70% of control values. Thus in spite of similar and low total serum lipid concentrations, differences in lipoprotein composition were found in the three different rheumatic diseases, underlining the importance of lipoprotein analyses in the study of dyslipoproteinaemia.", "contents": "Further studies on serum lipoproteins in connective tissue diseases. Men with ankylosing spondylitis (AS) and females with systemic lupus erythematosus (SLE) were found to have low total serum lipid concentrations similar to results previously obtained in patients with rheumatoid arthritis (RA). In AS men total serum TG was about 50% of control values and in AS men and SLE women total serum cholesterol was 78% of control values but close to corresponding RA concentrations. This was explained mainly by low LDL concentrations. There was a marked difference between RA patients and AS and SLE patients in that the two latter groups had normal HDL cholesterol concentrations whereas in RA patients the HDL cholesterol concentration was only 70% of control values. Thus in spite of similar and low total serum lipid concentrations, differences in lipoprotein composition were found in the three different rheumatic diseases, underlining the importance of lipoprotein analyses in the study of dyslipoproteinaemia."}
{"id": "PMID:213092", "title": "Neuromuscular refractoriness during blockage of transmission. A quantitative study.", "content": "The effects of suxamethonium and tubocurarine on the refractoriness of neuromuscular transmission were studied in 21 anaesthetized adult subjects under various levels of neuromuscular block. The ulnar nerve was stimulated every 12 s with twin supramaximal stimuli 4 ms apart. At any level of block, the refractory fraction (the fractional decrement of the compound electromyographic response of the adductor pollicis to the second twin stimulus, relative to the response to the first) was used to quantify neuromuscular refractoriness. The magnitude of block was determined by the response to the first stimulus. Correlation between refractoriness and the degree of block was sought. Without block, neuromuscular transmission averaged 23% (SEM 4) refractory with this twin interval. The refractory fraction was increased markedly by suxamethonium, reaching 0.69 (SEM 0.1) at 50% block. Complete refractoriness occurred during 25--75% block in eight of 11 instances. Tubocurarine did not significantly alter refractoriness, paired responses to the twin stimuli decreasing proportionately during block.", "contents": "Neuromuscular refractoriness during blockage of transmission. A quantitative study. The effects of suxamethonium and tubocurarine on the refractoriness of neuromuscular transmission were studied in 21 anaesthetized adult subjects under various levels of neuromuscular block. The ulnar nerve was stimulated every 12 s with twin supramaximal stimuli 4 ms apart. At any level of block, the refractory fraction (the fractional decrement of the compound electromyographic response of the adductor pollicis to the second twin stimulus, relative to the response to the first) was used to quantify neuromuscular refractoriness. The magnitude of block was determined by the response to the first stimulus. Correlation between refractoriness and the degree of block was sought. Without block, neuromuscular transmission averaged 23% (SEM 4) refractory with this twin interval. The refractory fraction was increased markedly by suxamethonium, reaching 0.69 (SEM 0.1) at 50% block. Complete refractoriness occurred during 25--75% block in eight of 11 instances. Tubocurarine did not significantly alter refractoriness, paired responses to the twin stimuli decreasing proportionately during block."}
{"id": "PMID:213093", "title": "Prolyl hydroxylase and collagen biosynthesis in rat liver following varying degrees of partial hepatectomy.", "content": "Prolyl hydroxylase activity and collagen biosynthesis have been measured at intervals following 2 extents of hepatic resection in rats. Prolyl hydroxylase activity is validated as a measure of collagen biosynthesis. The levels rise to a peak at 72 h and thereafter decline. The implications for the process of liver regeneration are discussed.", "contents": "Prolyl hydroxylase and collagen biosynthesis in rat liver following varying degrees of partial hepatectomy. Prolyl hydroxylase activity and collagen biosynthesis have been measured at intervals following 2 extents of hepatic resection in rats. Prolyl hydroxylase activity is validated as a measure of collagen biosynthesis. The levels rise to a peak at 72 h and thereafter decline. The implications for the process of liver regeneration are discussed."}
{"id": "PMID:213094", "title": "Studies on the effect of quartz, bentonite and coal dust mixtures on macrophages in vitro.", "content": "The effect of quartz, bentonite and coal dusts as well as the effect of the artificial mixture of these dusts on TTC reduction and extra-and intra-cellular lactate dehydrogenase activity in peritoneal rat macrophages was determined in vitro. The cell-membrane-damaging effect of quartz caused a significant extracellular release of lactate dehydrogenase. Bentonite caused no extracellular enzyme release, which leads us to believe that the biological effect of this dust is shown by decrease in intra-cellular lactate dehydrogenase activity. TTC reduction was inhibited equally by quartz and qentonite. In mixtures of quartz (60%)-bentonite (40%) dust the specific effect of quartz was inhibited by bentonite in vitro and also in vivo. We obtained the same results with coal-quartz-bentonite dust mixtures in vitro. Our experiments show that comparison of the biological effects of artificial dust mixtures and airborne dust samples is justified, and prove that performing various examinations simultaneously give fuller particulars on the probable biological effect of mineral dusts.", "contents": "Studies on the effect of quartz, bentonite and coal dust mixtures on macrophages in vitro. The effect of quartz, bentonite and coal dusts as well as the effect of the artificial mixture of these dusts on TTC reduction and extra-and intra-cellular lactate dehydrogenase activity in peritoneal rat macrophages was determined in vitro. The cell-membrane-damaging effect of quartz caused a significant extracellular release of lactate dehydrogenase. Bentonite caused no extracellular enzyme release, which leads us to believe that the biological effect of this dust is shown by decrease in intra-cellular lactate dehydrogenase activity. TTC reduction was inhibited equally by quartz and qentonite. In mixtures of quartz (60%)-bentonite (40%) dust the specific effect of quartz was inhibited by bentonite in vitro and also in vivo. We obtained the same results with coal-quartz-bentonite dust mixtures in vitro. Our experiments show that comparison of the biological effects of artificial dust mixtures and airborne dust samples is justified, and prove that performing various examinations simultaneously give fuller particulars on the probable biological effect of mineral dusts."}
{"id": "PMID:213095", "title": "A new syndrome with pigmentation, scleroderma, gynaecomastia, Raynaud's phenomenon and peripheral neuropathy.", "content": "A middle-aged man developed impotence, gynaecomastia, peripheral neuropathy, pigmentation lymphadenopathy, scleroderma, malabsorption and Raynaud's phenomenon following prolonged exposure to trichlorethylene. Somes, but not all, of these features have previously been reported in vinyl chloride disease, and trichlorethylene is related chemically to vinyl chloride. Seven patients with a similar but not identical syndrome have been described in Japan and U.S.A., apparently unrelated to exposure to industrial toxins.", "contents": "A new syndrome with pigmentation, scleroderma, gynaecomastia, Raynaud's phenomenon and peripheral neuropathy. A middle-aged man developed impotence, gynaecomastia, peripheral neuropathy, pigmentation lymphadenopathy, scleroderma, malabsorption and Raynaud's phenomenon following prolonged exposure to trichlorethylene. Somes, but not all, of these features have previously been reported in vinyl chloride disease, and trichlorethylene is related chemically to vinyl chloride. Seven patients with a similar but not identical syndrome have been described in Japan and U.S.A., apparently unrelated to exposure to industrial toxins."}
{"id": "PMID:213096", "title": "Cell membrane enzymes. II. Alkaline phosphatase and alkaline phosphodiesterase I in normal and leukaemic lymphocytes.", "content": "The distribution of two cell membrane enzymes, alkaline phosphatase and alkaline phosphodiesterase I has been studied in normal and leukaemic lymphocytes. No reduction in the level of activity of either enzyme was found in the chronic or acute B- and T-cell leukaemias. Alkaline phosphatase activity was elevated in the lymphocytes from T-CLL, cord blood and tonsils and the blast cells from Null-ALL. Alkaline phosphodiesterase was elevated in lymphocytes from cord blood and tonsils and the blast cells from Null-ALL. As findings in Null-ALL were based on only two cases, they need confirmation in a larger series. The significance of these results is discussed in relation to current theories of maturation and differentiation in the lymphoproliferative disorders.", "contents": "Cell membrane enzymes. II. Alkaline phosphatase and alkaline phosphodiesterase I in normal and leukaemic lymphocytes. The distribution of two cell membrane enzymes, alkaline phosphatase and alkaline phosphodiesterase I has been studied in normal and leukaemic lymphocytes. No reduction in the level of activity of either enzyme was found in the chronic or acute B- and T-cell leukaemias. Alkaline phosphatase activity was elevated in the lymphocytes from T-CLL, cord blood and tonsils and the blast cells from Null-ALL. Alkaline phosphodiesterase was elevated in lymphocytes from cord blood and tonsils and the blast cells from Null-ALL. As findings in Null-ALL were based on only two cases, they need confirmation in a larger series. The significance of these results is discussed in relation to current theories of maturation and differentiation in the lymphoproliferative disorders."}
{"id": "PMID:213097", "title": "Chemical modification studies on the Ca2+-dependent protein modulator: the role of methionine residues in the activation of cyclic nucleotide phosphodiesterase.", "content": "Methionine residues have been implicated in the activation of cyclic nucleotide phosphodiesterase by the Ca2+-dependent protein modulator [Walsh, M., & Stevens, F.C. (1977) Biochemistry 16,2742-2749]. Treatment of the modulator with N-chlorosuccinimide in the presence of Ca2+ resulted in selective oxidation of methionine residues at positions 71,72, 76, and, possibly, 109 in the modulator sequence. These residues lie on the surface of the molecule exposed to solvent. This modification has several effects on the modulator protein: (1) the Ca2+-binding properties of the oxidized modulator are changed with apparent loss of high-affinity binding sites, (2) the oxidized protein no longer interacts with phosphodiesterase, and (3) troponin C like activities, viz., Ca2+-dependent change in mobility on urea-polyacrylamide gel electrophoresis and formation of a urea-stable complex with troponin I, are lost upon oxidation of the modulator. The phosphodiesterase binding domain of the modulator protein appears to be located between the second and third Ca2+-binding loops, a region of the molecule known from previous partial proteolysis studies [Walsh, M., Stevens, F.C., Kuznicki, J., & Drabikowski, W.(1977), J. Biol. Chem. 252, 7440-7443] to be exposed in the presence of Ca2+.", "contents": "Chemical modification studies on the Ca2+-dependent protein modulator: the role of methionine residues in the activation of cyclic nucleotide phosphodiesterase. Methionine residues have been implicated in the activation of cyclic nucleotide phosphodiesterase by the Ca2+-dependent protein modulator [Walsh, M., & Stevens, F.C. (1977) Biochemistry 16,2742-2749]. Treatment of the modulator with N-chlorosuccinimide in the presence of Ca2+ resulted in selective oxidation of methionine residues at positions 71,72, 76, and, possibly, 109 in the modulator sequence. These residues lie on the surface of the molecule exposed to solvent. This modification has several effects on the modulator protein: (1) the Ca2+-binding properties of the oxidized modulator are changed with apparent loss of high-affinity binding sites, (2) the oxidized protein no longer interacts with phosphodiesterase, and (3) troponin C like activities, viz., Ca2+-dependent change in mobility on urea-polyacrylamide gel electrophoresis and formation of a urea-stable complex with troponin I, are lost upon oxidation of the modulator. The phosphodiesterase binding domain of the modulator protein appears to be located between the second and third Ca2+-binding loops, a region of the molecule known from previous partial proteolysis studies [Walsh, M., Stevens, F.C., Kuznicki, J., & Drabikowski, W.(1977), J. Biol. Chem. 252, 7440-7443] to be exposed in the presence of Ca2+."}
{"id": "PMID:213102", "title": "Fluorescence and chemical studies on the interaction of Escherichia coli DNA-binding protein with single-stranded DNA.", "content": "Nanosecond and steady-state fluorescence spectoscopy were used to probe the environment of the tryptophan residues of Escherichia coli DNA-binding protein. A spectral shift and a change in quantum yield of the protein upon binding to DNA or oligonucleotides indicate that the tryptophan residues are near or at the DNA binding site. The observation of two excited-state lifetimes of the protein indicates that there is heterogeneity in the microenvironments of these tryptophan residues. The \"short-lifetime\" tryptophan residues are more sensitive to the interaction with DNA than the \"long-lifetime\" residues. The results of solute-perturbation studies with iodide or acrylamide indicate that there are tryptophan residues near the surface of the protein which are heterogeneous in their accessibility to these quenchers and that they become less accessible after DNA binding. Also, lysine residues of the protein have been shown to be essential to DNA binding by chemical-modification studies. Tyrosine, arginine, and cysteine residues appear not to be involved in this binding process. From studies of the decay of fluorescence anisotropy of the binding protein in the presence and absence of DNA, it has been concluded that (a) the tetrameric binding protein does not dissociate into subuniits upon binding to the oligonucleotide d(pT)16 and (b) the binding protein-fd DNA complex possesses \"local flexibility\" and, therefore, cannot be described as a continuous, rigid rod.", "contents": "Fluorescence and chemical studies on the interaction of Escherichia coli DNA-binding protein with single-stranded DNA. Nanosecond and steady-state fluorescence spectoscopy were used to probe the environment of the tryptophan residues of Escherichia coli DNA-binding protein. A spectral shift and a change in quantum yield of the protein upon binding to DNA or oligonucleotides indicate that the tryptophan residues are near or at the DNA binding site. The observation of two excited-state lifetimes of the protein indicates that there is heterogeneity in the microenvironments of these tryptophan residues. The \"short-lifetime\" tryptophan residues are more sensitive to the interaction with DNA than the \"long-lifetime\" residues. The results of solute-perturbation studies with iodide or acrylamide indicate that there are tryptophan residues near the surface of the protein which are heterogeneous in their accessibility to these quenchers and that they become less accessible after DNA binding. Also, lysine residues of the protein have been shown to be essential to DNA binding by chemical-modification studies. Tyrosine, arginine, and cysteine residues appear not to be involved in this binding process. From studies of the decay of fluorescence anisotropy of the binding protein in the presence and absence of DNA, it has been concluded that (a) the tetrameric binding protein does not dissociate into subuniits upon binding to the oligonucleotide d(pT)16 and (b) the binding protein-fd DNA complex possesses \"local flexibility\" and, therefore, cannot be described as a continuous, rigid rod."}
{"id": "PMID:213101", "title": "Qualitative aspects of hydrogen-deuterium exchange in the 1H, 13C, and 15N nuclear magnetic resonance spectra of viomycin in aqueous solution.", "content": "The 1H, 13C, and 15N high field nuclear magnetic resonance spectra of the cyclic peptide viomycin have been fully assigned using homo- and heteronuclear double resonance experiments and pH effects. In addition it is shown how the two- and three-bond H-D isotope effects upon carbonyl resonances may assist in their assignment. The resistance to exchange with solvent water of the amide proton involved in the transannular hydrogen bond is observed directly in the 1H spectra, via the isotope effect on a carbonyl resonance in the 13C spectra, and via the one-bond 1H couppling in the 15N spectra.", "contents": "Qualitative aspects of hydrogen-deuterium exchange in the 1H, 13C, and 15N nuclear magnetic resonance spectra of viomycin in aqueous solution. The 1H, 13C, and 15N high field nuclear magnetic resonance spectra of the cyclic peptide viomycin have been fully assigned using homo- and heteronuclear double resonance experiments and pH effects. In addition it is shown how the two- and three-bond H-D isotope effects upon carbonyl resonances may assist in their assignment. The resistance to exchange with solvent water of the amide proton involved in the transannular hydrogen bond is observed directly in the 1H spectra, via the isotope effect on a carbonyl resonance in the 13C spectra, and via the one-bond 1H couppling in the 15N spectra."}
{"id": "PMID:213106", "title": "Transmembrane movement and distribution of cholesterol in the membrane of vesicular stomatitis virus.", "content": "The transmembrane movement and distribution of cholesterol in the vesicular stomatitis virus membrane were studied by following the depletion of cholesterol from virions to interacting phospholipid vesicles and by exchange of radiolabeled cholesterol between virions and phospholipid-cholesterol vesicles. The kinetics of the cholesterol exchange or depletion reactions revealed the presence of two exponential rates: a rapid rate, dependent on the vesicle to virus ratio, and a slower rate, independent of the vesicle to virus ratio. The kinetics of cholesterol movement could be best interpreted by a model of the virion membrane considered as a two pool system in which approximately 30% of the cholesterol resides in the outer monolayer and approximately 70% in the inner monolayer. The half-time for equilibration of the two pools was calculated to be 4--6 h and was assumed to represent the time required for transmembrane movement of cholesterol across the bilayer. The initial rate of transfer of cholesterol from virus into vesicles increased when vesicle phospholipids contained more unsaturated and shorter chain fatty acids. Furthermore, the transfer of cholesterol appeared to occur by a collisional mechanism requiring membrane-membrane contact. Interaction with lipid vesicles did not significantly affect the integrity of the virion membrane as assessed by the relative inaccessibility of internal proteins to lactoperoxidase-catalyzed iodination and by the small loss of [3H]amino acid labeled protein from the virus.", "contents": "Transmembrane movement and distribution of cholesterol in the membrane of vesicular stomatitis virus. The transmembrane movement and distribution of cholesterol in the vesicular stomatitis virus membrane were studied by following the depletion of cholesterol from virions to interacting phospholipid vesicles and by exchange of radiolabeled cholesterol between virions and phospholipid-cholesterol vesicles. The kinetics of the cholesterol exchange or depletion reactions revealed the presence of two exponential rates: a rapid rate, dependent on the vesicle to virus ratio, and a slower rate, independent of the vesicle to virus ratio. The kinetics of cholesterol movement could be best interpreted by a model of the virion membrane considered as a two pool system in which approximately 30% of the cholesterol resides in the outer monolayer and approximately 70% in the inner monolayer. The half-time for equilibration of the two pools was calculated to be 4--6 h and was assumed to represent the time required for transmembrane movement of cholesterol across the bilayer. The initial rate of transfer of cholesterol from virus into vesicles increased when vesicle phospholipids contained more unsaturated and shorter chain fatty acids. Furthermore, the transfer of cholesterol appeared to occur by a collisional mechanism requiring membrane-membrane contact. Interaction with lipid vesicles did not significantly affect the integrity of the virion membrane as assessed by the relative inaccessibility of internal proteins to lactoperoxidase-catalyzed iodination and by the small loss of [3H]amino acid labeled protein from the virus."}
{"id": "PMID:213107", "title": "Magnetic cross-relaxation among protons in protein solutions.", "content": "The magnetic spin-lattice relaxation rates of solvent water nuclei are known to increase upon addition of diamagnetic solute protein. This enhancement of the relaxation rate is a function of magnetic field, and the orientational relaxation time of the protein molecules can be deduced from analysis of the field-dependent relaxation rates. Although the nature of the interactions that convey information about the dynamics of protein motion to the solvent molecules is not established, it is known that there is a contribution to the relaxation rates of solvent protons that plays no role in the relaxation of solvent deuterons and 17O nuclei. We show here that the additional interaction arises from a cross-relaxation process between solvent and solute protons. We introduce a heuristic three-parameter model in which protein protons and solvent protons are considered as two separate thermodynamic systems that interact across the protein-solvent interface. The three parameters are the intrinsic relaxation rates of each system and a cross-relaxation term. The sign of the latter term must always be positive, for all values of magnetic field, in order for magnetization energy to flow from the hotter to the cooler system. We find that the magnetic field-dependence of the cross-relaxation contribution is much like that of the remaining solvent proton relaxation, i.e., about the same as the deuteron relaxation field dependence. This finding is not compatible with the predictions of expressions for the cross-relaxation that have been used by other authors, but not applied to data over a wide range of magnetic field strength. The model predicts that the relaxation behavior of both the protein protons and the solvent protons is the sum of two exponentials, the relative contributions of which would vary with protein concentration and solvent isotopic composition in a fashion suggestive of the presence of two classes of protein protons, when there is in reality only one. This finding has immediate implications for the interpretation of published proton relaxation rates in complex systems such as tissues; these data should be reexamined with cross-relaxation taken into account.", "contents": "Magnetic cross-relaxation among protons in protein solutions. The magnetic spin-lattice relaxation rates of solvent water nuclei are known to increase upon addition of diamagnetic solute protein. This enhancement of the relaxation rate is a function of magnetic field, and the orientational relaxation time of the protein molecules can be deduced from analysis of the field-dependent relaxation rates. Although the nature of the interactions that convey information about the dynamics of protein motion to the solvent molecules is not established, it is known that there is a contribution to the relaxation rates of solvent protons that plays no role in the relaxation of solvent deuterons and 17O nuclei. We show here that the additional interaction arises from a cross-relaxation process between solvent and solute protons. We introduce a heuristic three-parameter model in which protein protons and solvent protons are considered as two separate thermodynamic systems that interact across the protein-solvent interface. The three parameters are the intrinsic relaxation rates of each system and a cross-relaxation term. The sign of the latter term must always be positive, for all values of magnetic field, in order for magnetization energy to flow from the hotter to the cooler system. We find that the magnetic field-dependence of the cross-relaxation contribution is much like that of the remaining solvent proton relaxation, i.e., about the same as the deuteron relaxation field dependence. This finding is not compatible with the predictions of expressions for the cross-relaxation that have been used by other authors, but not applied to data over a wide range of magnetic field strength. The model predicts that the relaxation behavior of both the protein protons and the solvent protons is the sum of two exponentials, the relative contributions of which would vary with protein concentration and solvent isotopic composition in a fashion suggestive of the presence of two classes of protein protons, when there is in reality only one. This finding has immediate implications for the interpretation of published proton relaxation rates in complex systems such as tissues; these data should be reexamined with cross-relaxation taken into account."}
{"id": "PMID:213108", "title": "The role of lipid-protein interactions in NADH-cytochrome c reductase (rotenone-insensitive) of rat liver mitochondria.", "content": "The phospholipid depletion of rat liver mitochondria, induced by acetoneextraction or by digestion with phospholipase A2 or phospholipase C, greatly inhibited the activity of NADH-cytochrome c reductase (rotenone-insensitive). A great decrease of the reductase activity also occurred in isolated outer mitochondrial membranes after incubation with phospholipase A2. The enzyme activity was almost completely restored by the addition of a mixture of mitochondrial phospholipids to either lipid-deficient mitochondria, or lipid-deficient outer membranes. The individual phospholipids present in the outer mitochondrial membrane induced little or no stimulation of the reductase activity. Egg phosphatidylcholine was the most active phospholipid, but dipalmitoyl phosphatidylcholine was almost ineffective. The lipid depletion of mitochondria resulted in the disappearance of the non-linear Arrhenius plot which characterized the native reductase activity. A non-linear plot almost identical to that of the native enzyme was shown by the enzyme reconstituted with mitochondrial phospholipids. Triton X-100, Tween 80 or sodium deoxycholate induced only a small activation of NADH-cytochrome c reductase (rotenone-insensitive) in lipid-deficient mitochondria. The addition of cholesterol to extracted mitochondrial phospholipids at a 1 : 1 molar ratio inhibited the reactivation of NADH-cytochrome c reductase (rotenone-insensitive) but not the binding of phospholipids to lipid-deficient mitochondria or lipid-deficient outer membranes. These results show that NADH-cytochrome c reductase (rotenone-insensitive) of the outer mitochondrial membrane requires phospholipids for its activity. A mixture of phospholipids accomplishes this requirement better than individual phospholipids or detergents. It also seems that the membrane fluidity may influence the reductase activity.", "contents": "The role of lipid-protein interactions in NADH-cytochrome c reductase (rotenone-insensitive) of rat liver mitochondria. The phospholipid depletion of rat liver mitochondria, induced by acetoneextraction or by digestion with phospholipase A2 or phospholipase C, greatly inhibited the activity of NADH-cytochrome c reductase (rotenone-insensitive). A great decrease of the reductase activity also occurred in isolated outer mitochondrial membranes after incubation with phospholipase A2. The enzyme activity was almost completely restored by the addition of a mixture of mitochondrial phospholipids to either lipid-deficient mitochondria, or lipid-deficient outer membranes. The individual phospholipids present in the outer mitochondrial membrane induced little or no stimulation of the reductase activity. Egg phosphatidylcholine was the most active phospholipid, but dipalmitoyl phosphatidylcholine was almost ineffective. The lipid depletion of mitochondria resulted in the disappearance of the non-linear Arrhenius plot which characterized the native reductase activity. A non-linear plot almost identical to that of the native enzyme was shown by the enzyme reconstituted with mitochondrial phospholipids. Triton X-100, Tween 80 or sodium deoxycholate induced only a small activation of NADH-cytochrome c reductase (rotenone-insensitive) in lipid-deficient mitochondria. The addition of cholesterol to extracted mitochondrial phospholipids at a 1 : 1 molar ratio inhibited the reactivation of NADH-cytochrome c reductase (rotenone-insensitive) but not the binding of phospholipids to lipid-deficient mitochondria or lipid-deficient outer membranes. These results show that NADH-cytochrome c reductase (rotenone-insensitive) of the outer mitochondrial membrane requires phospholipids for its activity. A mixture of phospholipids accomplishes this requirement better than individual phospholipids or detergents. It also seems that the membrane fluidity may influence the reductase activity."}
{"id": "PMID:213109", "title": "Variable chlorophyll a fluorescence from P-700 enriched photosystem I particles dependent on the redox state of the reaction centre.", "content": "1. Photosystem I particles enriched in P-700 prepared by Triton X-100 treatment of chloroplasts show a light-induced increase in fluorescence yield of more than 100% in the presence of dithionite but not in its absence. 2. Steady state light maintains the P-700, of these particles, in the oxidised state when ascorbate is present but in the presence of dithionite only a transient oxidation occurs. 3 EPR data show that, in these particles, the primary electron acceptor (X) is maintained in the reduced state by light at room temperature only when the dithionite is also present. In contrast, the secondary electron acceptors are reduced in the dark by dithionite. 4. Fluorescence emission and excitation spectra and fluorescence lifetime measurements for the constant and variable fluorescence indicate a heterogeneity of the chlorophyll in these particles. 5. It is concluded that the variable fluorescence comes from those chlorophylls which can transfer their energy to the reaction centre and that the states PX and P+X are more effective quenchers of chlorophyll fluorescence than PX-, where P is P-700.", "contents": "Variable chlorophyll a fluorescence from P-700 enriched photosystem I particles dependent on the redox state of the reaction centre. 1. Photosystem I particles enriched in P-700 prepared by Triton X-100 treatment of chloroplasts show a light-induced increase in fluorescence yield of more than 100% in the presence of dithionite but not in its absence. 2. Steady state light maintains the P-700, of these particles, in the oxidised state when ascorbate is present but in the presence of dithionite only a transient oxidation occurs. 3 EPR data show that, in these particles, the primary electron acceptor (X) is maintained in the reduced state by light at room temperature only when the dithionite is also present. In contrast, the secondary electron acceptors are reduced in the dark by dithionite. 4. Fluorescence emission and excitation spectra and fluorescence lifetime measurements for the constant and variable fluorescence indicate a heterogeneity of the chlorophyll in these particles. 5. It is concluded that the variable fluorescence comes from those chlorophylls which can transfer their energy to the reaction centre and that the states PX and P+X are more effective quenchers of chlorophyll fluorescence than PX-, where P is P-700."}
{"id": "PMID:213110", "title": "Flash-induced photophosphorylation in Rhodospirillum rubrum chromatophores. I. The relationship between cytochrome c-420 content and photophosphorylation.", "content": "The content of cytochrome c-420 in Rhodospirillum rubrum chromatophores prepared by grinding with alumina is 5--10% of that in whole cells, and 20--40% in chromatophores by 'French' pressing. Flash-induced phosphorylation of various chromatophores which varied in cytochrome content from 7 to 40% is proportional to the cytochrome content. Extrapolating the cytochrome c-420 content to that observed in whole cells, a ratio ATP/P+X- near 1 is calculated. At low flash intensity the phosphorylation per flash is proportional to flash energy. Photophosphorylation in flashes given after a time of several minutes is only slightly dependent on the number of flashes. If the flashes are spaced from 0.1 to 10 s, relative phosphorylation in the first flash is about 70% and in the second 90+ of that observed in the following flashes. Proton binding is not affected by the cytochrome c-420 content and a ratio of H+/P+x- of 2.3 was found. These results can be explained by a working hypothesis in which charge separation occurring at one reaction centre and the resulting electron transport mediated amongst others by c-420, results in the injection of two protons into an ATPase, this in contrast to a chemiosmotic mechanism, where the protons are released in the chromatophore inner space.", "contents": "Flash-induced photophosphorylation in Rhodospirillum rubrum chromatophores. I. The relationship between cytochrome c-420 content and photophosphorylation. The content of cytochrome c-420 in Rhodospirillum rubrum chromatophores prepared by grinding with alumina is 5--10% of that in whole cells, and 20--40% in chromatophores by 'French' pressing. Flash-induced phosphorylation of various chromatophores which varied in cytochrome content from 7 to 40% is proportional to the cytochrome content. Extrapolating the cytochrome c-420 content to that observed in whole cells, a ratio ATP/P+X- near 1 is calculated. At low flash intensity the phosphorylation per flash is proportional to flash energy. Photophosphorylation in flashes given after a time of several minutes is only slightly dependent on the number of flashes. If the flashes are spaced from 0.1 to 10 s, relative phosphorylation in the first flash is about 70% and in the second 90+ of that observed in the following flashes. Proton binding is not affected by the cytochrome c-420 content and a ratio of H+/P+x- of 2.3 was found. These results can be explained by a working hypothesis in which charge separation occurring at one reaction centre and the resulting electron transport mediated amongst others by c-420, results in the injection of two protons into an ATPase, this in contrast to a chemiosmotic mechanism, where the protons are released in the chromatophore inner space."}
{"id": "PMID:213111", "title": "Pseudomonas cytochrome c peroxidase. Initial delay of the peroxidatic reaction. Electron transfer properties.", "content": "A delay of some seconds is observed in the reaction of Pseudomonas cytochrome c peroxidase if the reaction is initiated by adding the enzyme to the reaction mixture containing reduced electron donor and hydrogen peroxide. This lag phase is avoided if the enzyme is incubated with the reduced electron donor and the reaction is started by adding hydrogen peroxide. The nature of the initial delay has been studied and it is shown that the peroxidase is reduced before a steady-state rate in the peroxidatic reaction is reached. The ability of the peroxidase to accept electrons from various electron donors emphasizes its cytochrome-like properties.", "contents": "Pseudomonas cytochrome c peroxidase. Initial delay of the peroxidatic reaction. Electron transfer properties. A delay of some seconds is observed in the reaction of Pseudomonas cytochrome c peroxidase if the reaction is initiated by adding the enzyme to the reaction mixture containing reduced electron donor and hydrogen peroxide. This lag phase is avoided if the enzyme is incubated with the reduced electron donor and the reaction is started by adding hydrogen peroxide. The nature of the initial delay has been studied and it is shown that the peroxidase is reduced before a steady-state rate in the peroxidatic reaction is reached. The ability of the peroxidase to accept electrons from various electron donors emphasizes its cytochrome-like properties."}
{"id": "PMID:213112", "title": "Effects of inhibitors of lipid synthesis on the replication of Rous sarcoma virus. A specific effect of cerulenin on the processing of major non-glycosylated viral structural proteins.", "content": "The effects of two inhibitors of lipid biosynthesis on the replication of Rous sarcoma virus Prague C strain in chick embryo fibroblasts have been examined in media containing delipidated serum. 25-Hydroxycholestetate into sterols, had no effect on the formation of infectious virions or on the synthesis and processing of intracellular virion proteins. Cerulenin strongly inhibited [1(-14C)]acetate incorporation into fatty acids and partially inhibited its incorporation into sterols in chick embryo cells. Rous sarcoma virus production as measured by focus formation and by the production of [35S]methionine-labeled virions was strongly inhibited within 5 h after cerulenin addition to infected cultures. Examinatin of extracts of these cells revealed the accumulation of the 76 000 dalton precursor (Pr76) of the major non-glycosylated virion structural proteins, p27, p19, p15 and p12. The failure to process the 76 000 dalton precursor was coincident in time with the decrease in viron production. Neither whole serum nor mixtures of fatty acids plus cholesterol were able to reverse the effects of cerulenin.", "contents": "Effects of inhibitors of lipid synthesis on the replication of Rous sarcoma virus. A specific effect of cerulenin on the processing of major non-glycosylated viral structural proteins. The effects of two inhibitors of lipid biosynthesis on the replication of Rous sarcoma virus Prague C strain in chick embryo fibroblasts have been examined in media containing delipidated serum. 25-Hydroxycholestetate into sterols, had no effect on the formation of infectious virions or on the synthesis and processing of intracellular virion proteins. Cerulenin strongly inhibited [1(-14C)]acetate incorporation into fatty acids and partially inhibited its incorporation into sterols in chick embryo cells. Rous sarcoma virus production as measured by focus formation and by the production of [35S]methionine-labeled virions was strongly inhibited within 5 h after cerulenin addition to infected cultures. Examinatin of extracts of these cells revealed the accumulation of the 76 000 dalton precursor (Pr76) of the major non-glycosylated virion structural proteins, p27, p19, p15 and p12. The failure to process the 76 000 dalton precursor was coincident in time with the decrease in viron production. Neither whole serum nor mixtures of fatty acids plus cholesterol were able to reverse the effects of cerulenin."}
{"id": "PMID:213114", "title": "The influence of cellular amino acids and the Na+ : K+ pump on the membrane potential of the Ehrlich ascites tumor cell.", "content": "The membrane potential of the Ehrlich ascites tumor cell was shown to be influenced by its amino acid content and the activity of the Na+ :K+ pump. The membrane potential (monitored by the fluorescent dye, 3,3'-dipropylthiodicarbocyanine iodide) varied with the size of the endogenous amino acid pool and with the concentration of accumulated 2-aminoisobutyrate. When cellular amino acid content was high, the cells were hyperpolarized; as the pool declined in size, the cells were depolarized. The hyperpolarization seen with cellular amino acid required cellular Na+ but not cellular ATP. Na+ efflux was more rapid from cells containing 2-aminoisobutyrate than from cells low in internal amino acids. These observations indicate that the hyperpolarization recorded in cells with high cellular amino acid content resulted from the electrogenic co-efflux of Na+ and amino acids. Cellular ATP levels were found to decline rapidly in the presence of the dye and hence the influence of the pump was seen only if glucose was added to the cells. When the cells contained normal Na+ (approx. 30mM), the Na+ :K+ pump was shown to have little effect on the membrane potential (the addition of ouabain had little effect on the potential). When cellular Na+ was raised to 60mM, the activity of the pump changed the membrane potential from the range -25 to -30 mV to -44 to -63 mV. This hyperpolarization required external K+ and was inhibited by ouabain.", "contents": "The influence of cellular amino acids and the Na+ : K+ pump on the membrane potential of the Ehrlich ascites tumor cell. The membrane potential of the Ehrlich ascites tumor cell was shown to be influenced by its amino acid content and the activity of the Na+ :K+ pump. The membrane potential (monitored by the fluorescent dye, 3,3'-dipropylthiodicarbocyanine iodide) varied with the size of the endogenous amino acid pool and with the concentration of accumulated 2-aminoisobutyrate. When cellular amino acid content was high, the cells were hyperpolarized; as the pool declined in size, the cells were depolarized. The hyperpolarization seen with cellular amino acid required cellular Na+ but not cellular ATP. Na+ efflux was more rapid from cells containing 2-aminoisobutyrate than from cells low in internal amino acids. These observations indicate that the hyperpolarization recorded in cells with high cellular amino acid content resulted from the electrogenic co-efflux of Na+ and amino acids. Cellular ATP levels were found to decline rapidly in the presence of the dye and hence the influence of the pump was seen only if glucose was added to the cells. When the cells contained normal Na+ (approx. 30mM), the Na+ :K+ pump was shown to have little effect on the membrane potential (the addition of ouabain had little effect on the potential). When cellular Na+ was raised to 60mM, the activity of the pump changed the membrane potential from the range -25 to -30 mV to -44 to -63 mV. This hyperpolarization required external K+ and was inhibited by ouabain."}
{"id": "PMID:213115", "title": "Effects of adenosine 3' : 5'-monophosphate and guanosine 3' : 5'-monophosphate on calcium uptake and phosphorylation in membrane fractions of vascular smooth muscle.", "content": "The effects of adenosine 3' : 5'-monophosphate (cyclic AMP), guanosine 3' : 5'-monophosphate (cyclic GMP) and exogenous protein kinase on Ca uptake and membrane phosphorylation were studied in subcellular fractions of vascular smooth muscle from rabbit aorta. Two functionally distinct fractions were separated on a continuous sucrose gradient: a light fraction enriched in endoplasmic reticulum (fraction E) and a heavier fraction containing mainly plasma membranes (fraction P). While cyclic AMP and cyclic GMP had no effect on Ca uptake in the absence of oxalate, both cyclic nucleotides inhibited the rate of oxalate-activated Ca uptake when used at concentrations higher than 10(-5) M. The addition of bovine heart protein kinase to either fraction produced an increase in the rate of oxalate-activated Ca uptake which was further augmented by cyclic AMP. Cyclic GMP caused smaller stimulations of protein kinase-catalyzed Ca uptake than cyclic AMP. Mg-dependent phosphorylation, attributable to endogenous protein kinase(s), was inhibited in fraction E by low concentrations (10(-8) M) of both cyclic AMP and cyclic GMP. In fraction P, an inhibition by cyclic AMP occurred also at a concentration of 10(-8) M, while with cyclic AMP a concentration of 10(-5) M was required for a similar inhibition. Bovine heart protein kinase stimulated the phosphorylation of the membrane fractions much more than Ca uptake. In fraction E, in the presence of bovine protein kinase, both cyclic AMP and cyclic GMP stimulated phosphorylation up to 200%. Under these conditions, no stimulation was observed in fraction P. These results are compatible with the hypothesis that in vascular smooth muscle soluble rather than particulate protein kinases are involved in the regulation of intracellular Ca concentration.", "contents": "Effects of adenosine 3' : 5'-monophosphate and guanosine 3' : 5'-monophosphate on calcium uptake and phosphorylation in membrane fractions of vascular smooth muscle. The effects of adenosine 3' : 5'-monophosphate (cyclic AMP), guanosine 3' : 5'-monophosphate (cyclic GMP) and exogenous protein kinase on Ca uptake and membrane phosphorylation were studied in subcellular fractions of vascular smooth muscle from rabbit aorta. Two functionally distinct fractions were separated on a continuous sucrose gradient: a light fraction enriched in endoplasmic reticulum (fraction E) and a heavier fraction containing mainly plasma membranes (fraction P). While cyclic AMP and cyclic GMP had no effect on Ca uptake in the absence of oxalate, both cyclic nucleotides inhibited the rate of oxalate-activated Ca uptake when used at concentrations higher than 10(-5) M. The addition of bovine heart protein kinase to either fraction produced an increase in the rate of oxalate-activated Ca uptake which was further augmented by cyclic AMP. Cyclic GMP caused smaller stimulations of protein kinase-catalyzed Ca uptake than cyclic AMP. Mg-dependent phosphorylation, attributable to endogenous protein kinase(s), was inhibited in fraction E by low concentrations (10(-8) M) of both cyclic AMP and cyclic GMP. In fraction P, an inhibition by cyclic AMP occurred also at a concentration of 10(-8) M, while with cyclic AMP a concentration of 10(-5) M was required for a similar inhibition. Bovine heart protein kinase stimulated the phosphorylation of the membrane fractions much more than Ca uptake. In fraction E, in the presence of bovine protein kinase, both cyclic AMP and cyclic GMP stimulated phosphorylation up to 200%. Under these conditions, no stimulation was observed in fraction P. These results are compatible with the hypothesis that in vascular smooth muscle soluble rather than particulate protein kinases are involved in the regulation of intracellular Ca concentration."}
{"id": "PMID:213116", "title": "Plasma membranes from rat intestinal epithelial cells at different stages of maturation. I. Preparation and characterization of plasma membrane subfractions originating from crypt cells and from villous cells.", "content": "To determine the mechanism of the maturation of the brush border membrane in intestinal epithelial cells, purification of the plasma membrane from undifferentiated rat crypt cells and of the basal-lateral membrane from villous cells has been performed. The method is based on density perturbation of the mitochondria to selectively disrupt their association with the membrane. With both cell populations, two membrane subfractions displaying the same respective density on sucrose gradient have been obtained with an overall yield of 15--20% and a 10-fold enrichment of the plasma membrane markers 5'-nucleotidase and (Na+ + K+)-dependent, ouabain-sensitive ATPase chosen to follow their purification. The four fractions were constituted by sheets and apparently closed vesicles of various sizes. Each fraction was characterized by a distinct protein composition and different levels of enzyme activities. The cells, used for the preparation of the membranes, were isolated as a villus to crypt gradient. This separation and that of the membranes, led to the conclusion that the (Na+ + K+)-dependent ATPase is localized principally in the plasma membrane of all cells whatever their state of maturation, while 5'-nucleotidase is predominantly located in the basal-lateral membrane of the villous cells and may serve as a specific marker for the purification of this membrane. Finally it has been shown that aminopeptidase, dissacharidases and alkaline phosphatase do not appear simultaneously in the maturation process of the cells, alkaline phosphatase being absent from the crypt cells and aminopeptidase being the first to be synthesized. This enzyme seems to appear in the crypt cells membrane before being integrated into the mature brush border membrane.", "contents": "Plasma membranes from rat intestinal epithelial cells at different stages of maturation. I. Preparation and characterization of plasma membrane subfractions originating from crypt cells and from villous cells. To determine the mechanism of the maturation of the brush border membrane in intestinal epithelial cells, purification of the plasma membrane from undifferentiated rat crypt cells and of the basal-lateral membrane from villous cells has been performed. The method is based on density perturbation of the mitochondria to selectively disrupt their association with the membrane. With both cell populations, two membrane subfractions displaying the same respective density on sucrose gradient have been obtained with an overall yield of 15--20% and a 10-fold enrichment of the plasma membrane markers 5'-nucleotidase and (Na+ + K+)-dependent, ouabain-sensitive ATPase chosen to follow their purification. The four fractions were constituted by sheets and apparently closed vesicles of various sizes. Each fraction was characterized by a distinct protein composition and different levels of enzyme activities. The cells, used for the preparation of the membranes, were isolated as a villus to crypt gradient. This separation and that of the membranes, led to the conclusion that the (Na+ + K+)-dependent ATPase is localized principally in the plasma membrane of all cells whatever their state of maturation, while 5'-nucleotidase is predominantly located in the basal-lateral membrane of the villous cells and may serve as a specific marker for the purification of this membrane. Finally it has been shown that aminopeptidase, dissacharidases and alkaline phosphatase do not appear simultaneously in the maturation process of the cells, alkaline phosphatase being absent from the crypt cells and aminopeptidase being the first to be synthesized. This enzyme seems to appear in the crypt cells membrane before being integrated into the mature brush border membrane."}
{"id": "PMID:213117", "title": "Specific association of two homologous DNA-binding proteins to the native 30-S ribosomal subunits of Escherichia coli.", "content": "The native 30-S ribosomal subunits from Escherichia coli are shown to be associated with two proteins which are different from the known ribosome-associated and ribosomal proteins. Neither protein is foune on native 50-S subunits or on intact ribosomes in the cell extract. The purified proteins re-bind in vitro to free 30-S subunits, but do not bind to either free 50-S subunits or intact ribosomes. The proteins, denoted NS1 and NS2, have been purified and characterized. Both proteins showed the same molecular weight of 9500 by sodium dodecyl sulfate gel electrophoresis but 34 000 by gel filtration. Upon treatment with cross-linking reagents the purified proteins gave higher molecular weight species up to the tetrameric ones showing that they exist in solution as tetramers. The amino acid compositions, tryptic fingerprint patterns and N-terminal sequences of the two proteins have been determined. These data show that NS1 and NS2 possess distinct primary structures but with extensive sequence homology. Antibodies raised against the purified proteins cross-reacted in double immuno-diffusion tests confirming further the homology. Because of the similarity in properties a sample of the DNA-binding protein HD (Berthold, V. and Geider, K. (1976) Eur. J. Biochem. 71, 443--449) was compared to NS1 and NS2. In terms of several criteria, the protein HD is found to be a mixture of two proteins, namely NS1 and NS2. The present report is the first instance of an association of DNA-binding proteins to the ribosome.", "contents": "Specific association of two homologous DNA-binding proteins to the native 30-S ribosomal subunits of Escherichia coli. The native 30-S ribosomal subunits from Escherichia coli are shown to be associated with two proteins which are different from the known ribosome-associated and ribosomal proteins. Neither protein is foune on native 50-S subunits or on intact ribosomes in the cell extract. The purified proteins re-bind in vitro to free 30-S subunits, but do not bind to either free 50-S subunits or intact ribosomes. The proteins, denoted NS1 and NS2, have been purified and characterized. Both proteins showed the same molecular weight of 9500 by sodium dodecyl sulfate gel electrophoresis but 34 000 by gel filtration. Upon treatment with cross-linking reagents the purified proteins gave higher molecular weight species up to the tetrameric ones showing that they exist in solution as tetramers. The amino acid compositions, tryptic fingerprint patterns and N-terminal sequences of the two proteins have been determined. These data show that NS1 and NS2 possess distinct primary structures but with extensive sequence homology. Antibodies raised against the purified proteins cross-reacted in double immuno-diffusion tests confirming further the homology. Because of the similarity in properties a sample of the DNA-binding protein HD (Berthold, V. and Geider, K. (1976) Eur. J. Biochem. 71, 443--449) was compared to NS1 and NS2. In terms of several criteria, the protein HD is found to be a mixture of two proteins, namely NS1 and NS2. The present report is the first instance of an association of DNA-binding proteins to the ribosome."}
{"id": "PMID:213119", "title": "The phosphohydrolase activity in lamellar bodies and its relationship to phosphatidylglycerol and lung surfactant formation.", "content": "Phosphohydrolase activity of a lamellar body-enriched preparation from pig lung was examined to ascertain if two separate enzymes catalyze the hydrolysis of phosphatidic acid and phosphatidylglycerol 3-phosphate. From sulfhydryl inhibition, heat inactivation and substrate specificity studies, we suggest that one phosphohydrolase may account for the hydrolysis of both substrates. The relationship of the reported experiments to the biosynthesis of the glycerophospholipids present in surfactant is discussed.", "contents": "The phosphohydrolase activity in lamellar bodies and its relationship to phosphatidylglycerol and lung surfactant formation. Phosphohydrolase activity of a lamellar body-enriched preparation from pig lung was examined to ascertain if two separate enzymes catalyze the hydrolysis of phosphatidic acid and phosphatidylglycerol 3-phosphate. From sulfhydryl inhibition, heat inactivation and substrate specificity studies, we suggest that one phosphohydrolase may account for the hydrolysis of both substrates. The relationship of the reported experiments to the biosynthesis of the glycerophospholipids present in surfactant is discussed."}
{"id": "PMID:213120", "title": "Electron spin resonance studies of radicals obtained by the reaction of alpha-tocopherol and its model compound with superoxide ion.", "content": "alpha-Tocopherol (vitamin E) and its model compound, 6-hydroxy-2,2,5,7,8-pentamethylchroman, were found to be oxidized by O2- to yield free radicals which were detected at room temperature by ESR spectroscopy. The ESR spectra of these radicals showed seven main lines with additional hyperfine structure and have the same g-values at 2.0046. Assignments of the ESR spectra were done on the basis of the spectra of the free radicals of deuterated hydroxypentamethylchroman obtained from the same reaction with O2-. The radicals observed are chromanoxyls generated by the abstraction of hydrogen from the 6-hydroxy group of tocopherols.", "contents": "Electron spin resonance studies of radicals obtained by the reaction of alpha-tocopherol and its model compound with superoxide ion. alpha-Tocopherol (vitamin E) and its model compound, 6-hydroxy-2,2,5,7,8-pentamethylchroman, were found to be oxidized by O2- to yield free radicals which were detected at room temperature by ESR spectroscopy. The ESR spectra of these radicals showed seven main lines with additional hyperfine structure and have the same g-values at 2.0046. Assignments of the ESR spectra were done on the basis of the spectra of the free radicals of deuterated hydroxypentamethylchroman obtained from the same reaction with O2-. The radicals observed are chromanoxyls generated by the abstraction of hydrogen from the 6-hydroxy group of tocopherols."}
{"id": "PMID:213121", "title": "Nitrogenase from Bacillus polymyxa. Purification and properties of the component proteins.", "content": "A purification procedure is described for the components of Bacillus polymyxa nitrogenase. The procedure requires the removal of interfering mucopolysaccharides before the two nitrogenase proteins can be purified by the methods used with other nitrogenase components. The highest specific activities obtained were 2750 nmol C2H4 formed . min-1 . mg-1 MoFe protein and 2521 nmol C2H4 formed . min-1 . mg-1 Fe protein. The MoFe protein has a molecular weight of 215 000 and contains 2 molybdenum atoms, 33 iron atoms and 21 atoms of acid-labile sulfur per protein molecule. The Fe protein contains 3.2 iron atoms and 3.6 acid-labile sulfur atoms per molecule of 55 500 molecular weight. Each Fe protein binds two ATP molecules. The EPR spectra are similar to those of other nitrogenase proteins. MgATP changes the EPR of the Fe protein from a rhombic to an axial-type signal.", "contents": "Nitrogenase from Bacillus polymyxa. Purification and properties of the component proteins. A purification procedure is described for the components of Bacillus polymyxa nitrogenase. The procedure requires the removal of interfering mucopolysaccharides before the two nitrogenase proteins can be purified by the methods used with other nitrogenase components. The highest specific activities obtained were 2750 nmol C2H4 formed . min-1 . mg-1 MoFe protein and 2521 nmol C2H4 formed . min-1 . mg-1 Fe protein. The MoFe protein has a molecular weight of 215 000 and contains 2 molybdenum atoms, 33 iron atoms and 21 atoms of acid-labile sulfur per protein molecule. The Fe protein contains 3.2 iron atoms and 3.6 acid-labile sulfur atoms per molecule of 55 500 molecular weight. Each Fe protein binds two ATP molecules. The EPR spectra are similar to those of other nitrogenase proteins. MgATP changes the EPR of the Fe protein from a rhombic to an axial-type signal."}
{"id": "PMID:213122", "title": "Circular dichroism studies on cytochrome c peroxidase from baker's yeast (Saccharomyces cerevisiae).", "content": "Circular dichroism spectra of cytochrome c peroxidase from baker's yeast, those of the reduced enzyme, the carbonyl, cyanide and fluoride derivatives and the hydrogen peroxide compound, Compound I, have been recorded in the wavelength range 200 to 660 nm. All derivatives show negative Soret Cotton effects. The results suggest that the heme group is surrounded by tightly packed amino acid sidechains and that there is a histidine residue bound to the fifth coordination site of the heme iron. The native ferric enzyme is probably pentacoordinated. The circular dichroism spectra of the ligand compounds indicate that the ligands form a nonlinear bond to the heme iron as a result of steric hindrance in the vicinity of the heme. The spectrum of Compound I shows no perturbation of the porphyrin symmetry. The dichroic spectrum of the native enzyme in the far-ultraviolet wave-length region suggests that the secondary structure consists of roughly equal amounts of alpha-helical, beta-structure and unordered structure. After the removal of the heme group no great changes in the secondary structure can be observed.", "contents": "Circular dichroism studies on cytochrome c peroxidase from baker's yeast (Saccharomyces cerevisiae). Circular dichroism spectra of cytochrome c peroxidase from baker's yeast, those of the reduced enzyme, the carbonyl, cyanide and fluoride derivatives and the hydrogen peroxide compound, Compound I, have been recorded in the wavelength range 200 to 660 nm. All derivatives show negative Soret Cotton effects. The results suggest that the heme group is surrounded by tightly packed amino acid sidechains and that there is a histidine residue bound to the fifth coordination site of the heme iron. The native ferric enzyme is probably pentacoordinated. The circular dichroism spectra of the ligand compounds indicate that the ligands form a nonlinear bond to the heme iron as a result of steric hindrance in the vicinity of the heme. The spectrum of Compound I shows no perturbation of the porphyrin symmetry. The dichroic spectrum of the native enzyme in the far-ultraviolet wave-length region suggests that the secondary structure consists of roughly equal amounts of alpha-helical, beta-structure and unordered structure. After the removal of the heme group no great changes in the secondary structure can be observed."}
{"id": "PMID:213123", "title": "Conformation of corticotropin. An infrared spectrometry study of hydrogen exchange kinetics.", "content": "1H--2H exchange kinetics of the peptide hydrogens in corticotropin have been examined in 2H2O and CF3C2H2O2H solutions by means of infrared absorption measurements. In aqueous solution, around pH 3, the experimental data suggest a partially ordered structure, since in the two corticotropins 1--24 and 1--32 about 6 slowly exchanging peptide protons are numbered. These might belong to the N-terminal part of the molecule. The C-terminal 25--32 octapeptide segment appears to be unordered and slightly destabilizes the overall hormone conformation. For corticotropin1--24 in CF3C2H2O2H, the qualitative interpretation of infrared spectra and the quantitative analysis of exchange data give evidence of a strong stabilization: a predominantly alpha-helical structure is induced by trifluoroethanol.", "contents": "Conformation of corticotropin. An infrared spectrometry study of hydrogen exchange kinetics. 1H--2H exchange kinetics of the peptide hydrogens in corticotropin have been examined in 2H2O and CF3C2H2O2H solutions by means of infrared absorption measurements. In aqueous solution, around pH 3, the experimental data suggest a partially ordered structure, since in the two corticotropins 1--24 and 1--32 about 6 slowly exchanging peptide protons are numbered. These might belong to the N-terminal part of the molecule. The C-terminal 25--32 octapeptide segment appears to be unordered and slightly destabilizes the overall hormone conformation. For corticotropin1--24 in CF3C2H2O2H, the qualitative interpretation of infrared spectra and the quantitative analysis of exchange data give evidence of a strong stabilization: a predominantly alpha-helical structure is induced by trifluoroethanol."}
{"id": "PMID:213125", "title": "Comparison of polypeptides from cultured human fibroblasts and sarcoma cells.", "content": "The proteins in cell layers of cultured normal diploid human skin (ES, ER) and lung (WI-38) fibroblasts were compared to those of SV40-transformed human fibroblasts (WI-38/VA-13), human rhabdomyosarcoma (RD) and fibrosarcoma (HT-1080) cells using metabolic amino acid and sugar labeling and surface labeling with tritiated sodium borohydride after oxidation with galactose oxidase. The labeled proteins were analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography (fluorography). A transformation-associated decrease in the pericellular glycoprotein fibronectin (subunit molecular weight, 220 000) and in the synthesis of a set of polypeptides in the 130 000--180 000 dalton region was seen. Synthesis of a glycosylated 160 000 dalton polypeptide was markedly reduced. In transformed cells distinct increases of several specific polypeptides was detected in both [35S]methionine and [3H] mannose incorporation experiments but not using the surface labeling method.", "contents": "Comparison of polypeptides from cultured human fibroblasts and sarcoma cells. The proteins in cell layers of cultured normal diploid human skin (ES, ER) and lung (WI-38) fibroblasts were compared to those of SV40-transformed human fibroblasts (WI-38/VA-13), human rhabdomyosarcoma (RD) and fibrosarcoma (HT-1080) cells using metabolic amino acid and sugar labeling and surface labeling with tritiated sodium borohydride after oxidation with galactose oxidase. The labeled proteins were analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography (fluorography). A transformation-associated decrease in the pericellular glycoprotein fibronectin (subunit molecular weight, 220 000) and in the synthesis of a set of polypeptides in the 130 000--180 000 dalton region was seen. Synthesis of a glycosylated 160 000 dalton polypeptide was markedly reduced. In transformed cells distinct increases of several specific polypeptides was detected in both [35S]methionine and [3H] mannose incorporation experiments but not using the surface labeling method."}
{"id": "PMID:213126", "title": "The interaction of nitric oxide with soybean lipoxygenase-1.", "content": "The interaction of nitric oxide with the non-heme iron dioxygenase lipoxygenase is reported. This apparently resulted in a novel type of complex where an electron is donated to the NO molecule. In addition a new position for an EPR transition from iron was discovered which, it is suggested results from high spin ferric iron in a field of axial symmetry characterised by a very low value for D.", "contents": "The interaction of nitric oxide with soybean lipoxygenase-1. The interaction of nitric oxide with the non-heme iron dioxygenase lipoxygenase is reported. This apparently resulted in a novel type of complex where an electron is donated to the NO molecule. In addition a new position for an EPR transition from iron was discovered which, it is suggested results from high spin ferric iron in a field of axial symmetry characterised by a very low value for D."}
{"id": "PMID:213127", "title": "Factors regulating the induction of ornithine decarboxylase in fetal rat liver cells in culture.", "content": "Various hormonal and non-hormonal agents were tested for their ability to induce ornithine decarboxylase (EC 4.1.1.17) in primary cultures of fetal rat liver cells that retain many of the differentiated functions of hepatocytes. The only agents to induce ornithine decarboxylase in this cell type were fetal calf serum, prostaglandin E1 and cyclic AMP derivatives. Also, the amino acid arginine would induce ornithine decarboxylase in this cell type following arginine starvation for 24 h. These observations are in contrast to the wide range of hormones, e.g. insulin, hydrocortisone, glucagon and growth hormone, than can induce ornithine decarboxylase in vivo in the adult rat liver but which are all without effect on fetal rat liver cells.", "contents": "Factors regulating the induction of ornithine decarboxylase in fetal rat liver cells in culture. Various hormonal and non-hormonal agents were tested for their ability to induce ornithine decarboxylase (EC 4.1.1.17) in primary cultures of fetal rat liver cells that retain many of the differentiated functions of hepatocytes. The only agents to induce ornithine decarboxylase in this cell type were fetal calf serum, prostaglandin E1 and cyclic AMP derivatives. Also, the amino acid arginine would induce ornithine decarboxylase in this cell type following arginine starvation for 24 h. These observations are in contrast to the wide range of hormones, e.g. insulin, hydrocortisone, glucagon and growth hormone, than can induce ornithine decarboxylase in vivo in the adult rat liver but which are all without effect on fetal rat liver cells."}
{"id": "PMID:213128", "title": "The formation of hydroxyproline in collagen by cells grown in the absence of serum.", "content": "L-929 and 3T6 cells were conditioned to grow in a chemically defined medium lacking serum and ascorbate. Serum, when added, had a small stimulatory effect on the growth rate of the cells, but  ascorbate had no effect either on the growth rate or on the rate of protein synthesis. These cells were also shown to lack gulonolactone oxidase activity and therefore could not synthesize their own ascorbate. Nevertheless, in the absence of serum and ascorbate both cell types were able to hydroxylate peptidyl proline to an appreciable extent. This suggests that reductants other than ascorbate can at least partially satisfy the requirement for a reductant in the prolyl hydroxylase reaction in vivo.", "contents": "The formation of hydroxyproline in collagen by cells grown in the absence of serum. L-929 and 3T6 cells were conditioned to grow in a chemically defined medium lacking serum and ascorbate. Serum, when added, had a small stimulatory effect on the growth rate of the cells, but  ascorbate had no effect either on the growth rate or on the rate of protein synthesis. These cells were also shown to lack gulonolactone oxidase activity and therefore could not synthesize their own ascorbate. Nevertheless, in the absence of serum and ascorbate both cell types were able to hydroxylate peptidyl proline to an appreciable extent. This suggests that reductants other than ascorbate can at least partially satisfy the requirement for a reductant in the prolyl hydroxylase reaction in vivo."}
{"id": "PMID:213129", "title": "Effects of CuCl2 on the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart.", "content": "CuCl2 non-competitively inhibited the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent phosphodiesterase from bovine heart in the presence of 5 mM Mg2+, 10 muM Ca2+ and phosphodiesterase activator with Ki values of approximately 2 muM for both substrates. CuCl2 inhibition was also non-competitive with Mg2+, Ca2+ and phosphodiesterase activator. Dialysis demonstrated that CuCl2 inhibition is reversible. Treatment of the enzyme with p-hydroxymercuribenzoate resulted in the loss of enzyme activity, suggesting the presence of sulfhydryl groups essential for enzyme activity. The inhibitory activity of CuCl2 was not additive with that of p-hydroxymercuribenzoate, therefore CuCl2 may inhibit enzyme activity by binding to one or more essential sulfhydryl groups. CuCl2 also inhibited the hydrolysis of cyclic AMP by the cyclic AMP-specific phosphodiesterase from bovine heart with an I50 value of 18 muM. Several effects of Cu2+ are discussed which have been noted in other studies and might be due, in part, to changes in cyclic nucleotide levels following alterations in phosphodiesterase activity.", "contents": "Effects of CuCl2 on the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart. CuCl2 non-competitively inhibited the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent phosphodiesterase from bovine heart in the presence of 5 mM Mg2+, 10 muM Ca2+ and phosphodiesterase activator with Ki values of approximately 2 muM for both substrates. CuCl2 inhibition was also non-competitive with Mg2+, Ca2+ and phosphodiesterase activator. Dialysis demonstrated that CuCl2 inhibition is reversible. Treatment of the enzyme with p-hydroxymercuribenzoate resulted in the loss of enzyme activity, suggesting the presence of sulfhydryl groups essential for enzyme activity. The inhibitory activity of CuCl2 was not additive with that of p-hydroxymercuribenzoate, therefore CuCl2 may inhibit enzyme activity by binding to one or more essential sulfhydryl groups. CuCl2 also inhibited the hydrolysis of cyclic AMP by the cyclic AMP-specific phosphodiesterase from bovine heart with an I50 value of 18 muM. Several effects of Cu2+ are discussed which have been noted in other studies and might be due, in part, to changes in cyclic nucleotide levels following alterations in phosphodiesterase activity."}
{"id": "PMID:213130", "title": "Topical epinephrine causes a decrease in density of beta-adrenergic receptors and cathecholamine-stimulated chloride transport in the rabbit cornea.", "content": "A single administration, or twice daily administration for 4.5 days, of topical 2% epinephrine to the rabbit eye in vivo causes a 30-40% decrease in the density of beta-adrenergic receptors on membranes prepared from the cornea. Such treatment also causes complete loss of the ability of excised corneas to respond to epinephrine in vitro with enhanced active chloride transport. These findings indicate that stimulation with a high concentration of catecholamine depresses the entire pathway from receptor to physiological response.", "contents": "Topical epinephrine causes a decrease in density of beta-adrenergic receptors and cathecholamine-stimulated chloride transport in the rabbit cornea. A single administration, or twice daily administration for 4.5 days, of topical 2% epinephrine to the rabbit eye in vivo causes a 30-40% decrease in the density of beta-adrenergic receptors on membranes prepared from the cornea. Such treatment also causes complete loss of the ability of excised corneas to respond to epinephrine in vitro with enhanced active chloride transport. These findings indicate that stimulation with a high concentration of catecholamine depresses the entire pathway from receptor to physiological response."}
{"id": "PMID:213132", "title": "REM sleep and memory consolidation.", "content": "One proposal referring to a specific function of REM sleep has been that it is necessary for, or at least conductive to, the progress of memory consolidation. This hypothesis was tested by comparing the effects on story retention of REM deprivation against an S4 deprived control. It was found that recall accuracy following REM deprivation was significantly poorer than following S4 deprivation. Furthermore, the degree of deterioration in recall accuracy during REM recovery sleep was less than during S4 recovery sleep. These findings were interpreted as evidence for active REM facilitation of memory consolidation. However, alternative explanations based upon proactive influences need to be investigated.", "contents": "REM sleep and memory consolidation. One proposal referring to a specific function of REM sleep has been that it is necessary for, or at least conductive to, the progress of memory consolidation. This hypothesis was tested by comparing the effects on story retention of REM deprivation against an S4 deprived control. It was found that recall accuracy following REM deprivation was significantly poorer than following S4 deprivation. Furthermore, the degree of deterioration in recall accuracy during REM recovery sleep was less than during S4 recovery sleep. These findings were interpreted as evidence for active REM facilitation of memory consolidation. However, alternative explanations based upon proactive influences need to be investigated."}
{"id": "PMID:213133", "title": "A time-resolved electron spin resonance study of the oxidation of ascorbic acid by hydroxyl radical.", "content": "Time-resolved electron spin resonance (ESR) spectroscopy for the study of radicals produced by pulse radiolysis is illustrated by a study of the oxidation of ascorbic acid by OH radical in aqueous solution. In basic solution, the direct oxidation product, the ascorbate mono-anion radical, is formed within less than 2 mus of the radiolysis pulse. In acid solutions (pH 3(-4.5), N(2)O:saturated) three radicals are initially formed, the ascorbate mono-anion radical, an OH adduct seen also in steady-state ESR experiments, and an OH adduct at C2 with the main spin density at C3 of the ring. The first OH adduct decays with an initial half-life of about 100 mus, probably by biomolecular reaction. The second OH adduct, which shows one hyperfine splitting about a(H) = 24.4 +/- 0.3 G and g = 2.0031 +/- 0.0002, decays with a half-life of about 10 mus. On this same time scale the concentration of the ascorbate radical approximately doubles. It is concluded that the adduct at C2, but not the other adduct, loses water rapidly to form the ascorbate radical.", "contents": "A time-resolved electron spin resonance study of the oxidation of ascorbic acid by hydroxyl radical. Time-resolved electron spin resonance (ESR) spectroscopy for the study of radicals produced by pulse radiolysis is illustrated by a study of the oxidation of ascorbic acid by OH radical in aqueous solution. In basic solution, the direct oxidation product, the ascorbate mono-anion radical, is formed within less than 2 mus of the radiolysis pulse. In acid solutions (pH 3(-4.5), N(2)O:saturated) three radicals are initially formed, the ascorbate mono-anion radical, an OH adduct seen also in steady-state ESR experiments, and an OH adduct at C2 with the main spin density at C3 of the ring. The first OH adduct decays with an initial half-life of about 100 mus, probably by biomolecular reaction. The second OH adduct, which shows one hyperfine splitting about a(H) = 24.4 +/- 0.3 G and g = 2.0031 +/- 0.0002, decays with a half-life of about 10 mus. On this same time scale the concentration of the ascorbate radical approximately doubles. It is concluded that the adduct at C2, but not the other adduct, loses water rapidly to form the ascorbate radical."}
{"id": "PMID:213135", "title": "Fast electron transfer processes in cytochrome C and related metalloproteins.", "content": "Various free radicals formed on pulse radiolysis of aqueous solutions have been used to investigate the mechanisms of reduction of cytochrome(III) c by inter- and intramolecular electron transfer. The rapid formation of free radicals (t less than 1 mus) and their high reactivity with cytochrome (k approximately 10(8)(-5) x 10(10)M(-1)s(-1)) make such studies feasible. Reduction of cytochrome by free radicls is monitored by optical methods. Fast optical changes in the 1(-500)-mus region correspond to reduction of the iron center; whereas the slower changes in the 10(-500)-ms region are attributed to postreduction conformational changes. It has been concluded that the reduction path is mediated through the crevice and that no reduction intermediates are being formed.", "contents": "Fast electron transfer processes in cytochrome C and related metalloproteins. Various free radicals formed on pulse radiolysis of aqueous solutions have been used to investigate the mechanisms of reduction of cytochrome(III) c by inter- and intramolecular electron transfer. The rapid formation of free radicals (t less than 1 mus) and their high reactivity with cytochrome (k approximately 10(8)(-5) x 10(10)M(-1)s(-1)) make such studies feasible. Reduction of cytochrome by free radicls is monitored by optical methods. Fast optical changes in the 1(-500)-mus region correspond to reduction of the iron center; whereas the slower changes in the 10(-500)-ms region are attributed to postreduction conformational changes. It has been concluded that the reduction path is mediated through the crevice and that no reduction intermediates are being formed."}
{"id": "PMID:213136", "title": "Fast reactions in carbon monoxide binding to heme proteins.", "content": "Using fast flash photolysis, we have measured the binding of CO to carboxymethylated cytochrome c and to heme c octapeptide as a function of temperature (5 degrees-350 degreesK) over an extended time range (100 ns(-1) ks). Experiments used a microsecond dye laser (lambda = 540 nm), and a mode-locked frequency-doubled Nd-glass laser (lambda = 530 nm). At low temperatures (5 degrees-120 degreesK) the rebinding exhibits two components. The slower component (I) is nonexponential in time and has an optical spectrum corresponding to rebiding from an S = 2, CO-free deoxy state. The fast component (I*) is exponential in time with a lifetime shorter than 10 mus and an optical spectrum different from the slow component. In myoglobin and the separated alpha and beta chains of hemoglobin, only process I is visible. The optical absorption spectrum of I* and its time dependence suggest that it may correspond to recombination from an excited state in which the iron has not yet moved out of the heme plane. The temperature dependences of both processes have been measured. Both occur via quantum mechanical tunneling at the lowest temperatures and via over-the-barrier motion at higher temperatures.", "contents": "Fast reactions in carbon monoxide binding to heme proteins. Using fast flash photolysis, we have measured the binding of CO to carboxymethylated cytochrome c and to heme c octapeptide as a function of temperature (5 degrees-350 degreesK) over an extended time range (100 ns(-1) ks). Experiments used a microsecond dye laser (lambda = 540 nm), and a mode-locked frequency-doubled Nd-glass laser (lambda = 530 nm). At low temperatures (5 degrees-120 degreesK) the rebinding exhibits two components. The slower component (I) is nonexponential in time and has an optical spectrum corresponding to rebiding from an S = 2, CO-free deoxy state. The fast component (I*) is exponential in time with a lifetime shorter than 10 mus and an optical spectrum different from the slow component. In myoglobin and the separated alpha and beta chains of hemoglobin, only process I is visible. The optical absorption spectrum of I* and its time dependence suggest that it may correspond to recombination from an excited state in which the iron has not yet moved out of the heme plane. The temperature dependences of both processes have been measured. Both occur via quantum mechanical tunneling at the lowest temperatures and via over-the-barrier motion at higher temperatures."}
{"id": "PMID:213139", "title": "Modeling the role of cyclic AMP in catabolite repression of inducible enzyme biosynthesis in microbial cells.", "content": "Modeling the role of cyclic AMP (cAMP) in catabolite repression of inducible enzyme production in microbial cells was studied. A catabolite repression index, F, was defined based on the postulation that complex formation occurs between RNA polymerase (RNAP) and DNA, and shifting from the inert form to the open form of this complex (the latter form is required for transcription) is accelerated by the cAMP.CRP complex. The catabolite repression index, F, was incorporated into model equations of mRNA production. Empirical relationships between intracellular cAMP level and medium glucose concentration were established based on experimental data and introduced into the model. Computer simulation results were obtained for a number of interesting cases. The practical utility of the proposed model was demonstrated by comparing it with the experimental results on glucose isomerase biosynthesis.", "contents": "Modeling the role of cyclic AMP in catabolite repression of inducible enzyme biosynthesis in microbial cells. Modeling the role of cyclic AMP (cAMP) in catabolite repression of inducible enzyme production in microbial cells was studied. A catabolite repression index, F, was defined based on the postulation that complex formation occurs between RNA polymerase (RNAP) and DNA, and shifting from the inert form to the open form of this complex (the latter form is required for transcription) is accelerated by the cAMP.CRP complex. The catabolite repression index, F, was incorporated into model equations of mRNA production. Empirical relationships between intracellular cAMP level and medium glucose concentration were established based on experimental data and introduced into the model. Computer simulation results were obtained for a number of interesting cases. The practical utility of the proposed model was demonstrated by comparing it with the experimental results on glucose isomerase biosynthesis."}
{"id": "PMID:213140", "title": "Sex steroid production by the human fetus: its role in morphogenesis and control by gonadotropins.", "content": "Normal male genital differentiation requires fetal testicular secretion of both testosterone and the nonsteroidal m\u00fcllerian-inhibitory factor. It appears that secretion of testosterone, at least during the critical period of differentiation, occurs in response to stimulation by CG, although pituitary LG may influence Leydig cell function in later fetal life. To date, there is no evidence to support a similar endocrine function for the fetal ovary in female genital differentiation. In both sexes normal fetal pituitary gonadotropin secretion appears to be required for maturation of the germ cells and related elements. The pattern of FSH and LH secretion in the fetus reflects gradual maturation of a functional hypothalamo-pituitary unit responsive to feedback inhibition by sex steroids. The higher levels of gonadotropins in female fetuses from from 12--20 weeks suggest either that this maturation occurs earlier in males than in females, or, more probably, that feedback recognition of androgens is established before gestation reflects development of an estrogen-mediated feedback mechanism, and in addition the possible influence that hormones, such as prolactin or placental estradiol, may have on testicular steroidogenesis.", "contents": "Sex steroid production by the human fetus: its role in morphogenesis and control by gonadotropins. Normal male genital differentiation requires fetal testicular secretion of both testosterone and the nonsteroidal m\u00fcllerian-inhibitory factor. It appears that secretion of testosterone, at least during the critical period of differentiation, occurs in response to stimulation by CG, although pituitary LG may influence Leydig cell function in later fetal life. To date, there is no evidence to support a similar endocrine function for the fetal ovary in female genital differentiation. In both sexes normal fetal pituitary gonadotropin secretion appears to be required for maturation of the germ cells and related elements. The pattern of FSH and LH secretion in the fetus reflects gradual maturation of a functional hypothalamo-pituitary unit responsive to feedback inhibition by sex steroids. The higher levels of gonadotropins in female fetuses from from 12--20 weeks suggest either that this maturation occurs earlier in males than in females, or, more probably, that feedback recognition of androgens is established before gestation reflects development of an estrogen-mediated feedback mechanism, and in addition the possible influence that hormones, such as prolactin or placental estradiol, may have on testicular steroidogenesis."}
{"id": "PMID:213141", "title": "[Electrophysiologic, morphometric and histocytochemical characteristics of frog sartorius muscle fibers].", "content": "Three groups of muscle fibers (dark, light, and intermediate) were revealed in the fibers of the frog sartorius muscle in examination of the succinate dehydrogenase (SDH) activity. There was revealed a reverse relationship between the diameter of the muscle fibers an the SDH activity in them. The external surface of sartorius muscle is chiefly represented by dark muscle fibers, whereas the internal one--by light ones. Microelectrode study demonstrated that the fibers of the external surface were characterized, in comparison with those of the internal one, by lesser action potentials, prolonged trace negative potential, low quant composition of the end plate potentials, high amplitude and low frequency of the end plate miniature potentials. Analysis of the data obtained demonstrated definite interrelationship between the histochemical profile of the muscle fibers of the frog sartorius muscle and their electrophysiological characteristics.", "contents": "[Electrophysiologic, morphometric and histocytochemical characteristics of frog sartorius muscle fibers]. Three groups of muscle fibers (dark, light, and intermediate) were revealed in the fibers of the frog sartorius muscle in examination of the succinate dehydrogenase (SDH) activity. There was revealed a reverse relationship between the diameter of the muscle fibers an the SDH activity in them. The external surface of sartorius muscle is chiefly represented by dark muscle fibers, whereas the internal one--by light ones. Microelectrode study demonstrated that the fibers of the external surface were characterized, in comparison with those of the internal one, by lesser action potentials, prolonged trace negative potential, low quant composition of the end plate potentials, high amplitude and low frequency of the end plate miniature potentials. Analysis of the data obtained demonstrated definite interrelationship between the histochemical profile of the muscle fibers of the frog sartorius muscle and their electrophysiological characteristics."}
{"id": "PMID:213142", "title": "[Biochemical characteristics of the synaptosomes and mitochondria of the motor area of the cerebral cortex following switching off of sensory impulsation].", "content": "Changes in the specific activity of cytochrome oxidase, monoamine oxidase, acetylcholinesterase and Na,K-ATPase in the light and heavy synaptosomes and mitochondria of neurone bodies fractions in the motor cerebral cortex of rabbits were demonstrated under conditions of light (visual) deprivation. These changes were specific of different metabolic cycles and differed in individual cell ultrastructures. The influence of sensory impulsation on functional neuron activity in different projection regions of the cerebral cortex is discussed.", "contents": "[Biochemical characteristics of the synaptosomes and mitochondria of the motor area of the cerebral cortex following switching off of sensory impulsation]. Changes in the specific activity of cytochrome oxidase, monoamine oxidase, acetylcholinesterase and Na,K-ATPase in the light and heavy synaptosomes and mitochondria of neurone bodies fractions in the motor cerebral cortex of rabbits were demonstrated under conditions of light (visual) deprivation. These changes were specific of different metabolic cycles and differed in individual cell ultrastructures. The influence of sensory impulsation on functional neuron activity in different projection regions of the cerebral cortex is discussed."}
{"id": "PMID:213143", "title": "[Enzymatic lipid peroxidation and oxidative metabolism of aminazine in brain microsomal fractions].", "content": "NAD (P) H-dependent enzymic systems, both of lipid peroxidation and chlorpromazine oxidative metabolism are shown to be localized in the microsomal fractions from human and rat brain. Hydroxy-derivatives of chlorpromazine (e.g. 7-OH-chlorpromazine) formed in the course of enzymic NADPH-dependent metabolism possess antioxidant activity and inhibit lipid peroxidation in the brain microsomes. The properties of enzymic NAD (P) H-dependent oxigenase systems in the membranes of the microsomal reticulum of the liver and brain are compared.", "contents": "[Enzymatic lipid peroxidation and oxidative metabolism of aminazine in brain microsomal fractions]. NAD (P) H-dependent enzymic systems, both of lipid peroxidation and chlorpromazine oxidative metabolism are shown to be localized in the microsomal fractions from human and rat brain. Hydroxy-derivatives of chlorpromazine (e.g. 7-OH-chlorpromazine) formed in the course of enzymic NADPH-dependent metabolism possess antioxidant activity and inhibit lipid peroxidation in the brain microsomes. The properties of enzymic NAD (P) H-dependent oxigenase systems in the membranes of the microsomal reticulum of the liver and brain are compared."}
{"id": "PMID:213144", "title": "[Effect of bradykinin and morphine on rat sensomotor cortex neurons].", "content": "As revealed in acute experiments on rats bradykinin applied microiontophoretically produced neuronal activation in the sensory-motor region of the rat brain cortex. Morphine applied iontophoretically prevented bradykinin effect. It is suggested that bradykinin interacts with opiate receptors in the cortical neurones.", "contents": "[Effect of bradykinin and morphine on rat sensomotor cortex neurons]. As revealed in acute experiments on rats bradykinin applied microiontophoretically produced neuronal activation in the sensory-motor region of the rat brain cortex. Morphine applied iontophoretically prevented bradykinin effect. It is suggested that bradykinin interacts with opiate receptors in the cortical neurones."}
{"id": "PMID:213145", "title": "[Functional activity of rat adenohypophysis cells in a primary monolayer culture and the effect of several regulators on it].", "content": "Some peculiarities of labeled growth hormone (GH) and prolactin (PL) secretion in the 5-day monolayer culture of the rat adenohypophysis was studied. The hormones from the culture medium were obtained by electrophoresis on polyacrylamide gel. Natrium-dibutyril of cyclic adenosine-3',5'-monophosphate and theophylline, stimulated the GH and PL secretion. Thyrotropin-releasing hormone (TRH) increased the incorporation of 14C-1-leucine into the cell protein, stimulated PL secretion, but did not act on the GH release. Somatostatin completely abolished the GH secretion mediated by theophyllin, but not that of PL. Some peculiarities in the formation of labeled GH and PL pool in the cells and secretion of these hormones into the culture medium are discussed.", "contents": "[Functional activity of rat adenohypophysis cells in a primary monolayer culture and the effect of several regulators on it]. Some peculiarities of labeled growth hormone (GH) and prolactin (PL) secretion in the 5-day monolayer culture of the rat adenohypophysis was studied. The hormones from the culture medium were obtained by electrophoresis on polyacrylamide gel. Natrium-dibutyril of cyclic adenosine-3',5'-monophosphate and theophylline, stimulated the GH and PL secretion. Thyrotropin-releasing hormone (TRH) increased the incorporation of 14C-1-leucine into the cell protein, stimulated PL secretion, but did not act on the GH release. Somatostatin completely abolished the GH secretion mediated by theophyllin, but not that of PL. Some peculiarities in the formation of labeled GH and PL pool in the cells and secretion of these hormones into the culture medium are discussed."}
{"id": "PMID:213146", "title": "[Enzymatic micromethod for determining Na, K-ATPase activity in rat cerebral cortex membranes].", "content": "A method for the assay of Na,K-ATPase activity of unpurified synaptosomal fraction obtained from the microquantities (2--3 mg of fresh tissue) of the rat cerebral cortex is described. This method is based on the fluorimetric determination of ADP formed in the course of ATPase reaction. The method is highly sensitive and may be used to determine the membrane preparations Na,K-ATPase activity with the protein content of 0.05--10.0 microgram per sample.", "contents": "[Enzymatic micromethod for determining Na, K-ATPase activity in rat cerebral cortex membranes]. A method for the assay of Na,K-ATPase activity of unpurified synaptosomal fraction obtained from the microquantities (2--3 mg of fresh tissue) of the rat cerebral cortex is described. This method is based on the fluorimetric determination of ADP formed in the course of ATPase reaction. The method is highly sensitive and may be used to determine the membrane preparations Na,K-ATPase activity with the protein content of 0.05--10.0 microgram per sample."}
{"id": "PMID:213147", "title": "The effect of dbcAMP on the lysolecithin induced hemolysis of calf and adult cattle erythrocytes.", "content": "The calf erythrocytes have an increased sensitivity against lysolecithin as compared to their adult counterparts. 10(-3)M dbcAMP increases the hemolysis induced by 5 microgram of lysolecithin in 0.15 M NaCl containing 10 mM phosphate buffer (pH 7.4). By increasing the level of phosphate buffer (75 mM) in the incubation mixture, 10(-3)M dbcAMP decreases the hemolysis induced by 5 microgram of lysolecithin. These data suggest a dual effect exerted by dcbAMP: the relatively labilizing or stabilizing effect prevails as a function of exogenous inorganic phosphate level. 10(-6)M dcbAMP also has a relative protective effect against lysolecithin. The combined addition of cAMP (10(-3)) and theophyllin (10(-4)M) does not stabilize the membrane. By increasing the level of lysolecithin to 20 microgram/ml the stabilizing effect of dcbAMP disappears. DbcAMP (10(-3)) as well as cAMP (10(-3)M) and theophyllin (10(-4)M) have a minimum increasing effect on hemolysis in the absence of lysolecithin, too.", "contents": "The effect of dbcAMP on the lysolecithin induced hemolysis of calf and adult cattle erythrocytes. The calf erythrocytes have an increased sensitivity against lysolecithin as compared to their adult counterparts. 10(-3)M dbcAMP increases the hemolysis induced by 5 microgram of lysolecithin in 0.15 M NaCl containing 10 mM phosphate buffer (pH 7.4). By increasing the level of phosphate buffer (75 mM) in the incubation mixture, 10(-3)M dbcAMP decreases the hemolysis induced by 5 microgram of lysolecithin. These data suggest a dual effect exerted by dcbAMP: the relatively labilizing or stabilizing effect prevails as a function of exogenous inorganic phosphate level. 10(-6)M dcbAMP also has a relative protective effect against lysolecithin. The combined addition of cAMP (10(-3)) and theophyllin (10(-4)M) does not stabilize the membrane. By increasing the level of lysolecithin to 20 microgram/ml the stabilizing effect of dcbAMP disappears. DbcAMP (10(-3)) as well as cAMP (10(-3)M) and theophyllin (10(-4)M) have a minimum increasing effect on hemolysis in the absence of lysolecithin, too."}
{"id": "PMID:213148", "title": "Effect of mercuric chloride on the digestive system of a teleost fish, Channa punctatus.", "content": "The effect of 1.8 mg/liter (LC50) of mercuric chloride exposure on the activities of alkaline phosphatase, acid phosphatase, glucose-6-phosphatase, amylase, pepsin, trypsin, tripeptidase glycyl-glycine dipeptidase and carnosinase has been examined in Channa punctatus. The three phosphatases have been inhibited in the liver but showed an increase in activity in the intestine and pyloric caeca. Amylase, pepsin and trypsin have also shown a slight increase in activity. There has been no significant alteration in the activites of the peptidases. The results show that mercury inhibits the activites of phosphatases in the liver but has no significant effect on the digestive enzymes within the experimental period of 96 hours.", "contents": "Effect of mercuric chloride on the digestive system of a teleost fish, Channa punctatus. The effect of 1.8 mg/liter (LC50) of mercuric chloride exposure on the activities of alkaline phosphatase, acid phosphatase, glucose-6-phosphatase, amylase, pepsin, trypsin, tripeptidase glycyl-glycine dipeptidase and carnosinase has been examined in Channa punctatus. The three phosphatases have been inhibited in the liver but showed an increase in activity in the intestine and pyloric caeca. Amylase, pepsin and trypsin have also shown a slight increase in activity. There has been no significant alteration in the activites of the peptidases. The results show that mercury inhibits the activites of phosphatases in the liver but has no significant effect on the digestive enzymes within the experimental period of 96 hours."}
{"id": "PMID:213149", "title": "The neuropathology of malignant external otitis.", "content": "A case report of malignant external otitis is presented with particular emphasis on the neuropathological sequelae. The most striking finding was a mycotic aneurysm of the basilar artery with resultant thrombosis and brain stem infarction. Diffuse pachymeningitis was also present. The severity of the changes described in this case further point out the need for early recognition and adequate treatment of this potentially fatal disease complex.", "contents": "The neuropathology of malignant external otitis. A case report of malignant external otitis is presented with particular emphasis on the neuropathological sequelae. The most striking finding was a mycotic aneurysm of the basilar artery with resultant thrombosis and brain stem infarction. Diffuse pachymeningitis was also present. The severity of the changes described in this case further point out the need for early recognition and adequate treatment of this potentially fatal disease complex."}
{"id": "PMID:213151", "title": "Adjuvant chemotherapy: an approach to the management of malignant disease.", "content": "The definition of the roles of surgery and radiation therapy in controlling local malignant disease has become much clearer in the past two decades. Nonetheless, most patients who die of their malignancy do so from metastatic disease. With the advent of effective combination chemotherapy for many patients with advanced malignant disease, the employment of systemic treatment at an earlier stage has become a clinical possibility. Important advances in the systemic control of a number of malignancies have been described. These are examples of a few of the presently ongoing trials (Salmon and Jones, 1977). For the merits and demerits of prophylactic systemic treatments to be accurately determined in malignant disease, it is important that the future role of adjuvant chemotherapy in man be evaluated only in the context of carefully controlled clinical trials. The fact that adjuvant therapy is effective in prolonging survival in some malignant diseases is established; its role in many of the commoner malignant diseases awaits more complete evaluation.", "contents": "Adjuvant chemotherapy: an approach to the management of malignant disease. The definition of the roles of surgery and radiation therapy in controlling local malignant disease has become much clearer in the past two decades. Nonetheless, most patients who die of their malignancy do so from metastatic disease. With the advent of effective combination chemotherapy for many patients with advanced malignant disease, the employment of systemic treatment at an earlier stage has become a clinical possibility. Important advances in the systemic control of a number of malignancies have been described. These are examples of a few of the presently ongoing trials (Salmon and Jones, 1977). For the merits and demerits of prophylactic systemic treatments to be accurately determined in malignant disease, it is important that the future role of adjuvant chemotherapy in man be evaluated only in the context of carefully controlled clinical trials. The fact that adjuvant therapy is effective in prolonging survival in some malignant diseases is established; its role in many of the commoner malignant diseases awaits more complete evaluation."}
{"id": "PMID:213154", "title": "Adrenocorticotrophic hormone fragments mimic the effect of morphine in vitro.", "content": "1 Fragments of the N terminal part of adrenocorticotrophic hormone (ACTH) inhibited the electrically evoked contractions of the mouse vas deferens. This inhibition could be antagonized by naloxone. 2 The same fragments displaced radiolabelled morphine from morphine antiserum. 3 Structure-activity relationship studies showed that in both assay systems the active core is located within the sequence ACTH 7--10. 4 It is postulated that the Trp9 residue and the peptide bond between Trp9 and Gly10 are particularly important for interaction of ACTH fragments with morphine receptors.", "contents": "Adrenocorticotrophic hormone fragments mimic the effect of morphine in vitro. 1 Fragments of the N terminal part of adrenocorticotrophic hormone (ACTH) inhibited the electrically evoked contractions of the mouse vas deferens. This inhibition could be antagonized by naloxone. 2 The same fragments displaced radiolabelled morphine from morphine antiserum. 3 Structure-activity relationship studies showed that in both assay systems the active core is located within the sequence ACTH 7--10. 4 It is postulated that the Trp9 residue and the peptide bond between Trp9 and Gly10 are particularly important for interaction of ACTH fragments with morphine receptors."}
{"id": "PMID:213162", "title": "Genital herpesvirus infection in women attending a venereal diseases clinic.", "content": "Routine cervical viral cultures (and cultures from lesions if present) were performed on 2630 female patients attending a venereal diseases clinic over a period of four years. Of these patients 96 (3.7%) had genital herpetic infection; of these 23 (24%) were asymptomatic. The association of herpesvirus with other genital infections is considered, but no increase in the incidence of Neisseria gonorrhoeae, Trichomonas vaginalis, and genital warts was found; there was an increased incidence of Candida albicans. A significantly higher percentage of the patients with herpesvirus took oral contraceptives. The findings are discussed and compared with previous reports.", "contents": "Genital herpesvirus infection in women attending a venereal diseases clinic. Routine cervical viral cultures (and cultures from lesions if present) were performed on 2630 female patients attending a venereal diseases clinic over a period of four years. Of these patients 96 (3.7%) had genital herpetic infection; of these 23 (24%) were asymptomatic. The association of herpesvirus with other genital infections is considered, but no increase in the incidence of Neisseria gonorrhoeae, Trichomonas vaginalis, and genital warts was found; there was an increased incidence of Candida albicans. A significantly higher percentage of the patients with herpesvirus took oral contraceptives. The findings are discussed and compared with previous reports."}
{"id": "PMID:213163", "title": "Sensory action potentials and biopsy of the sural nerve in neuropathy.", "content": "In 167 consecutive patients with various types of neuropathy, the amplitude of the sensory potential and the maximum conduction velocity along the sural nerve were compared with conduction in other sensory nerves, and were related to structural changes revealed by nerve biopsy. Electrophysiological findings in the sural nerve were similar to those in the superficial peroneal and the median nerve, though the distal segment of the median nerve was normal in 20 per cent of the patients when it was abnormal in the sural nerve. Quantitation of histological findings was a more sensitive method than the electrophysiological study in that two-thirds of 33 patients with normal electrophysiology in the sural nerve showed mild loss of fibres or signs of remyelination in teased fibres. The amplitude of the sensory potential was grossly related to the number of large myelinated fibres (more than 7 micrometer in diameter). Considering the 95 nerves from which teased fibres were obtained, maximum conduction velocity was abnormal in half. In 18 of these nerves, slowing in conduction was due to axonal degeneration: the velocity was as to be expected from the diameter of the largest fibres in the biopsy (\"proportionate slowing\"). In 9 nerves slowing was severe and more marked than to be expected from loss of the largest fibres (\"disproportionate slowing\"); these nerves showed paranodal or segmental demyelination in more than 30 per cent of the fibres. In 16 nerves from patients with neuropathy of different aetiology neither loss of fibres nor demyelination could explain the moderate slowing. The cause of slowing in these nerves is unknown; other conditions are referred to in which slowing in conduction cannot be attributed to morphological changes. Finally, electrophysiological and histological findings are reported in some patients with neuropathy associated with malignant neoplasm, with rheumatoid arthritis, with polyarteritis nodosa, with acute intermittent porphyria and with cirrhosis of the liver.", "contents": "Sensory action potentials and biopsy of the sural nerve in neuropathy. In 167 consecutive patients with various types of neuropathy, the amplitude of the sensory potential and the maximum conduction velocity along the sural nerve were compared with conduction in other sensory nerves, and were related to structural changes revealed by nerve biopsy. Electrophysiological findings in the sural nerve were similar to those in the superficial peroneal and the median nerve, though the distal segment of the median nerve was normal in 20 per cent of the patients when it was abnormal in the sural nerve. Quantitation of histological findings was a more sensitive method than the electrophysiological study in that two-thirds of 33 patients with normal electrophysiology in the sural nerve showed mild loss of fibres or signs of remyelination in teased fibres. The amplitude of the sensory potential was grossly related to the number of large myelinated fibres (more than 7 micrometer in diameter). Considering the 95 nerves from which teased fibres were obtained, maximum conduction velocity was abnormal in half. In 18 of these nerves, slowing in conduction was due to axonal degeneration: the velocity was as to be expected from the diameter of the largest fibres in the biopsy (\"proportionate slowing\"). In 9 nerves slowing was severe and more marked than to be expected from loss of the largest fibres (\"disproportionate slowing\"); these nerves showed paranodal or segmental demyelination in more than 30 per cent of the fibres. In 16 nerves from patients with neuropathy of different aetiology neither loss of fibres nor demyelination could explain the moderate slowing. The cause of slowing in these nerves is unknown; other conditions are referred to in which slowing in conduction cannot be attributed to morphological changes. Finally, electrophysiological and histological findings are reported in some patients with neuropathy associated with malignant neoplasm, with rheumatoid arthritis, with polyarteritis nodosa, with acute intermittent porphyria and with cirrhosis of the liver."}
{"id": "PMID:213164", "title": "Hypersensitivity to histamine in the guinea-pig brain: microiontophoretic and biochemical studies.", "content": "Electrolytic lesions of the medial forebrain bundle induce a fall in histidine decarboxylase activity (the specific synthetic enzyme of brain histamine) in the ipsilateral cerebral cortex and hippocampus of the guinea pig brain; these results suggest the presence of an ascending histaminergic pathway in the guinea pig brain similar to that described in the rat. Possible alterations in the sensitivity of histaminergic receptors present in the target areas were studied following this type of lesion by combining electrophysiological and biochemical approaches. Microiontophoretic applications of histamine or noradrenaline reveal a hypersensitivity (lower ejecting currents for threshold and maximal responses) in cortical neurons ipsilateral but not contralateral to the lesion, whereas responses to iontophoretically applied GABA are not modified. In contrast the responsiveness of histamine-sensitive cyclic AMP generating systems is not modified, neither in the cerebral cortex nor in the hippocampus after this type of lesion. Similar conclusions are reached from the data obtained with specific agonists of the two classes of histaminergic receptors and measurements in the presence of a phosphodiesterase inhibitor. Several hypotheses are discussed in order to reconcile the finding of a denervation hypersensitivity revealed by iontophoresis contrasting with an unaltered responsiveness of the histaminergic receptors linked to the adenylate cyclase.", "contents": "Hypersensitivity to histamine in the guinea-pig brain: microiontophoretic and biochemical studies. Electrolytic lesions of the medial forebrain bundle induce a fall in histidine decarboxylase activity (the specific synthetic enzyme of brain histamine) in the ipsilateral cerebral cortex and hippocampus of the guinea pig brain; these results suggest the presence of an ascending histaminergic pathway in the guinea pig brain similar to that described in the rat. Possible alterations in the sensitivity of histaminergic receptors present in the target areas were studied following this type of lesion by combining electrophysiological and biochemical approaches. Microiontophoretic applications of histamine or noradrenaline reveal a hypersensitivity (lower ejecting currents for threshold and maximal responses) in cortical neurons ipsilateral but not contralateral to the lesion, whereas responses to iontophoretically applied GABA are not modified. In contrast the responsiveness of histamine-sensitive cyclic AMP generating systems is not modified, neither in the cerebral cortex nor in the hippocampus after this type of lesion. Similar conclusions are reached from the data obtained with specific agonists of the two classes of histaminergic receptors and measurements in the presence of a phosphodiesterase inhibitor. Several hypotheses are discussed in order to reconcile the finding of a denervation hypersensitivity revealed by iontophoresis contrasting with an unaltered responsiveness of the histaminergic receptors linked to the adenylate cyclase."}
{"id": "PMID:213171", "title": "Role of the locus coeruleus in transmission onto anterior colliculus neurons.", "content": "The present study was an attempt to elucidate the role of locus coeruleus (LC) on neuronal activities in the anterior colliculus of rats anesthetized with alpha-chloralose. The spike latency of neurons in the deep grey and white layers of anterior colliculus elicited by stimulation of the optic chiasm (OC), lateral geniculate body (LGB) and visual cortex (VC) was longer than that of neurons in the more superficial layers: optic and intermediate grey layers. When conditioning stimuli were applied to LC, a significant inhibition of spike generation upon OC, LGB and VC stimulation was observed on neurons of deep grey and white layers, but not on those of optic and intermediate grey layers. The conditioning stimulation did not alter spike generation, either in the neurons of deep grey  and white layers or those of optic and intermediate grey layers, following stimulation of the superficial grey layer. These results strongly suggest that noradrenaline originating in the LC could produce an inhibition of neuronal activities in the deep grey and white layers, and such is probably the result of inhibition of neurons located in the superficial layer of the anterior colliculus.", "contents": "Role of the locus coeruleus in transmission onto anterior colliculus neurons. The present study was an attempt to elucidate the role of locus coeruleus (LC) on neuronal activities in the anterior colliculus of rats anesthetized with alpha-chloralose. The spike latency of neurons in the deep grey and white layers of anterior colliculus elicited by stimulation of the optic chiasm (OC), lateral geniculate body (LGB) and visual cortex (VC) was longer than that of neurons in the more superficial layers: optic and intermediate grey layers. When conditioning stimuli were applied to LC, a significant inhibition of spike generation upon OC, LGB and VC stimulation was observed on neurons of deep grey and white layers, but not on those of optic and intermediate grey layers. The conditioning stimulation did not alter spike generation, either in the neurons of deep grey  and white layers or those of optic and intermediate grey layers, following stimulation of the superficial grey layer. These results strongly suggest that noradrenaline originating in the LC could produce an inhibition of neuronal activities in the deep grey and white layers, and such is probably the result of inhibition of neurons located in the superficial layer of the anterior colliculus."}
{"id": "PMID:213172", "title": "Reflex activity of regenerating frog spinal motoneurons.", "content": "The reflex activity of frog spinal motoneurons whose axons had been sectioned 7 days to 10 months previously was examined. Before the severed axons reinnervated muscle, reflex latency was prolonged, and reflex amplitude was depressed. Examination of input-output relations revealed the presence of a subset of axotomized motoneurons having supranormal excitability. This subset was not present in normal preparations or in preparations tested after reinnervation took place. Following reinnervation of muscle, reflex latency returned to preoperative levels, while amplitude recovery was typically more variable. Decreased conduction velocity of the severed ventral root fibers accounted for the alterations in reflex latency. These and other data form the basis for concluding that motoneurons, even within a particular preparation, show a wide range of responses to section of their axons and will provide a framework for interpretation of more selective intracellular experiments.", "contents": "Reflex activity of regenerating frog spinal motoneurons. The reflex activity of frog spinal motoneurons whose axons had been sectioned 7 days to 10 months previously was examined. Before the severed axons reinnervated muscle, reflex latency was prolonged, and reflex amplitude was depressed. Examination of input-output relations revealed the presence of a subset of axotomized motoneurons having supranormal excitability. This subset was not present in normal preparations or in preparations tested after reinnervation took place. Following reinnervation of muscle, reflex latency returned to preoperative levels, while amplitude recovery was typically more variable. Decreased conduction velocity of the severed ventral root fibers accounted for the alterations in reflex latency. These and other data form the basis for concluding that motoneurons, even within a particular preparation, show a wide range of responses to section of their axons and will provide a framework for interpretation of more selective intracellular experiments."}
{"id": "PMID:213173", "title": "Regional distribution of angiotensinogen in rat brain.", "content": "The regional distribution of angiotensinogen, the prohormone of angiotensin I, was examined in rat brain. Quantification of brain angiotensinogen concentration was difficult because of the presence of an endogenous angiotensin I degrading (i.e. angiotensinase) activity which was active at the pH of the renin-angiotensinogen incubation. This degrading activity was unequally distributed throughout the brain, and its presence in homogenates invalidated measured levels of angiotensinogen. Only following removal of the angiotensinase activity by ammonium sulfate precipitation of the prohormone could the distribution of the prohormone be determined. Angiotensinogen was widely distributed throughout 31 brain regions; however there was an approximate 12-fold variation in concentration. Highest levels of the prohormone were found in the dorsal and ventral periventricular hypothalamus, area postrema, organum vasculosum lamina terminalis, periventricular thalamus, dorsal raphe and lateral reticular formation. Significantly lower amounts were found in the parietal cortex, cerebellum, septum and pituitaries. While the majority of regions examined exhibited similar concentrations of angiotensinogen, the demonstration of regions containing either significnatly low or high amounts of prohormone is consistent with a topographical distribution of angiotensinogen in rat brain.", "contents": "Regional distribution of angiotensinogen in rat brain. The regional distribution of angiotensinogen, the prohormone of angiotensin I, was examined in rat brain. Quantification of brain angiotensinogen concentration was difficult because of the presence of an endogenous angiotensin I degrading (i.e. angiotensinase) activity which was active at the pH of the renin-angiotensinogen incubation. This degrading activity was unequally distributed throughout the brain, and its presence in homogenates invalidated measured levels of angiotensinogen. Only following removal of the angiotensinase activity by ammonium sulfate precipitation of the prohormone could the distribution of the prohormone be determined. Angiotensinogen was widely distributed throughout 31 brain regions; however there was an approximate 12-fold variation in concentration. Highest levels of the prohormone were found in the dorsal and ventral periventricular hypothalamus, area postrema, organum vasculosum lamina terminalis, periventricular thalamus, dorsal raphe and lateral reticular formation. Significantly lower amounts were found in the parietal cortex, cerebellum, septum and pituitaries. While the majority of regions examined exhibited similar concentrations of angiotensinogen, the demonstration of regions containing either significnatly low or high amounts of prohormone is consistent with a topographical distribution of angiotensinogen in rat brain."}
{"id": "PMID:213174", "title": "Effects of acetylcholine and cyclic GMP on input resistance of cortical neurons in awake cats.", "content": "The effects on input resistance (Rm) of extracellular iontophoresis of acetylcholine (ACh) and of intracellular iontophoresis of cyclic GMP (cGMP) were studied in neurons of the coronal-pericruciate cortex of awake cats. Control studies were also conducted including iontophoresis of saline extracellularly and 5'-GMP intracellularly. (1) Substantial increases in Rm occurred in approximately half the neurons given ACh or cGMP. (2) In the absence of associated repetitive spike discharge induced by intracellular injection of depolarizing current pulses during iontophoretic applications, the increases in Rm were transient occurring in less than 30 sec and lasting 4--5 min. (3) With associated current-induced spike discharge, the increases in Rm persisted for as long as the neurons could be held -- up to 1.5 h maximally. (4) Rm was not increased if saline was substituted for ACh, if 5'-GMP was substituted for cGMP, or if the neuron was only discharged repeatedly. (5) The magnitude and time course of both transient and persistent increases in Rm were comparable between cells given ACh or cGMP and whether action potentials and resting potentials were greater than or equal to 40 mV (average 47 mV)* or were less.", "contents": "Effects of acetylcholine and cyclic GMP on input resistance of cortical neurons in awake cats. The effects on input resistance (Rm) of extracellular iontophoresis of acetylcholine (ACh) and of intracellular iontophoresis of cyclic GMP (cGMP) were studied in neurons of the coronal-pericruciate cortex of awake cats. Control studies were also conducted including iontophoresis of saline extracellularly and 5'-GMP intracellularly. (1) Substantial increases in Rm occurred in approximately half the neurons given ACh or cGMP. (2) In the absence of associated repetitive spike discharge induced by intracellular injection of depolarizing current pulses during iontophoretic applications, the increases in Rm were transient occurring in less than 30 sec and lasting 4--5 min. (3) With associated current-induced spike discharge, the increases in Rm persisted for as long as the neurons could be held -- up to 1.5 h maximally. (4) Rm was not increased if saline was substituted for ACh, if 5'-GMP was substituted for cGMP, or if the neuron was only discharged repeatedly. (5) The magnitude and time course of both transient and persistent increases in Rm were comparable between cells given ACh or cGMP and whether action potentials and resting potentials were greater than or equal to 40 mV (average 47 mV)* or were less."}
{"id": "PMID:213175", "title": "Ligand binding studies in the mouse olfactory bulb: identification and characterization of a L-[3H]carnosine binding site.", "content": "Binding sites for the dipeptide L-carnosine (beta-alanyl-L-histidine) have been detected in membranes prepared from mouse olfactory bulbs. The binding of L-[3H]-carnosine was saturable, reversible and stereospecific and had a Kd of about 770 nM. The stereospecific binding of L-carnosine represented about 30% of the total binding at pH 6.8, and decreased markedly with increasing pH. Binding was stimulated by calcium, unaffected by zinc, magnesium or manganese and inhibited by sodium and potassium. Carnosine binding was sensitive to trypsin and phospholipases A and C, but not to neuraminidase. Nystatin and filipin, which interact with membrane lipids, also interferred with binding. Some peptide analogues of carnosine were potent inhibitors of binding, but a variety of drugs serving as potent inhibitors in other binding systems had no effect on carnosine binding. Carnosine binding to mouse olfactory bulb membranes was 15-fold higher than that seen in membranes prepared from cerebral hemispheres, 5-fold higher than that seen in membranes prepared from cerebral hemispheres, 5-fold higher than in cerebellum membranes and 3-fold higher than in membranes from spinal medulla and the olfactory tubercle-lateral olfactory tract area. Binding sites for 6 other radiolabeled receptor ligands were also detected in bulb membranes. Peripheral deafferentation of the olfactory bulbs by intranasal irrigation with ZnSO4 led to a loss greater than 90% of the L-[3H]carnosine binding in 4--5 days with much smaller losses in binding of the other 6 ligands over a 180-day observation period. This initial loss of carnosine binding after denervation was due to a loss of binding site stereo-specificity followed by a loss of binding sites. The characteristics of the carnosine binding site in olfactory bulb fulfil 6 of the 7 criteria considered relevant for a functional receptor.", "contents": "Ligand binding studies in the mouse olfactory bulb: identification and characterization of a L-[3H]carnosine binding site. Binding sites for the dipeptide L-carnosine (beta-alanyl-L-histidine) have been detected in membranes prepared from mouse olfactory bulbs. The binding of L-[3H]-carnosine was saturable, reversible and stereospecific and had a Kd of about 770 nM. The stereospecific binding of L-carnosine represented about 30% of the total binding at pH 6.8, and decreased markedly with increasing pH. Binding was stimulated by calcium, unaffected by zinc, magnesium or manganese and inhibited by sodium and potassium. Carnosine binding was sensitive to trypsin and phospholipases A and C, but not to neuraminidase. Nystatin and filipin, which interact with membrane lipids, also interferred with binding. Some peptide analogues of carnosine were potent inhibitors of binding, but a variety of drugs serving as potent inhibitors in other binding systems had no effect on carnosine binding. Carnosine binding to mouse olfactory bulb membranes was 15-fold higher than that seen in membranes prepared from cerebral hemispheres, 5-fold higher than that seen in membranes prepared from cerebral hemispheres, 5-fold higher than in cerebellum membranes and 3-fold higher than in membranes from spinal medulla and the olfactory tubercle-lateral olfactory tract area. Binding sites for 6 other radiolabeled receptor ligands were also detected in bulb membranes. Peripheral deafferentation of the olfactory bulbs by intranasal irrigation with ZnSO4 led to a loss greater than 90% of the L-[3H]carnosine binding in 4--5 days with much smaller losses in binding of the other 6 ligands over a 180-day observation period. This initial loss of carnosine binding after denervation was due to a loss of binding site stereo-specificity followed by a loss of binding sites. The characteristics of the carnosine binding site in olfactory bulb fulfil 6 of the 7 criteria considered relevant for a functional receptor."}
{"id": "PMID:213179", "title": "Effect of 1,25-dihydroxycholecalciferol on adenosine 3',5'-cyclic monophosphate production in calvaria of mice.", "content": "1,25-dihydroxycholecalciferol (1,25-(OH)2D3), added at doses which stimulate bone resorption in the system used, did not increase adenosine 3',5'-cyclic monophosphate (cAMP) production in vitro in mouse calvaria incubated for up to 48 h. Thus 1,25-(OH)2D3 does not appear to stimulate bone resorption through involvement of an increased cAMP production.", "contents": "Effect of 1,25-dihydroxycholecalciferol on adenosine 3',5'-cyclic monophosphate production in calvaria of mice. 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), added at doses which stimulate bone resorption in the system used, did not increase adenosine 3',5'-cyclic monophosphate (cAMP) production in vitro in mouse calvaria incubated for up to 48 h. Thus 1,25-(OH)2D3 does not appear to stimulate bone resorption through involvement of an increased cAMP production."}
{"id": "PMID:213180", "title": "Direct lymphocytotoxicity against herpes simplex virus infected cells.", "content": "This study was undertaken to determine if direct cytotoxicity (DC) against herpes simplex virus infected cells, perhaps mediated by T cells, could be demonstrated in individuals subject to recurrent herpes labialis. The mononuclear cells from 7 out of 17 individuals with recurrent herpes expressed DC whereas no DC was ever exhibited by 7 individuals without a previous history of herpes infections. Several approaches were used to show that the cytotoxicity being detected was predominately of the direct type rather than antibody-dependent cell cytotoxicity (ADCC). Since the effector cells of the DC were sensitive to trypsin treatment and behaved as do natural killer (NK) cells upon cell fractionation, the results were taken to imply that the DC was attributable to a NK-effector cell type rather than a classical T lymphocyte.", "contents": "Direct lymphocytotoxicity against herpes simplex virus infected cells. This study was undertaken to determine if direct cytotoxicity (DC) against herpes simplex virus infected cells, perhaps mediated by T cells, could be demonstrated in individuals subject to recurrent herpes labialis. The mononuclear cells from 7 out of 17 individuals with recurrent herpes expressed DC whereas no DC was ever exhibited by 7 individuals without a previous history of herpes infections. Several approaches were used to show that the cytotoxicity being detected was predominately of the direct type rather than antibody-dependent cell cytotoxicity (ADCC). Since the effector cells of the DC were sensitive to trypsin treatment and behaved as do natural killer (NK) cells upon cell fractionation, the results were taken to imply that the DC was attributable to a NK-effector cell type rather than a classical T lymphocyte."}
{"id": "PMID:213176", "title": "Involvement of ACTH and MSH in active and passive avoidance behavior.", "content": "Intracerebroventricular injection of antiserum to alpha--MSH induces a weak reduction of passive avoidance latencies after administration prior to retention testing. Administration of antiserum to ACTH 1--24 induces a more marked effect in this respect, whereas injection of a combination of these antisera results in the strongest reduction of passive avoidance retention. No effect of this treatment is observed when these antisera are injected immediately after the learning trial. In active avoidance behavior a facilitation of extinction of the response is observed after intracerebroventricular administration of the antisera prior to each extinction session. This effect is comparable with the one observed in passive avoidance behavior. From these data it is suggested that ACTH and alpha-MSH play an important role in processes related to the retrieval of information stored in the brain.", "contents": "Involvement of ACTH and MSH in active and passive avoidance behavior. Intracerebroventricular injection of antiserum to alpha--MSH induces a weak reduction of passive avoidance latencies after administration prior to retention testing. Administration of antiserum to ACTH 1--24 induces a more marked effect in this respect, whereas injection of a combination of these antisera results in the strongest reduction of passive avoidance retention. No effect of this treatment is observed when these antisera are injected immediately after the learning trial. In active avoidance behavior a facilitation of extinction of the response is observed after intracerebroventricular administration of the antisera prior to each extinction session. This effect is comparable with the one observed in passive avoidance behavior. From these data it is suggested that ACTH and alpha-MSH play an important role in processes related to the retrieval of information stored in the brain."}
{"id": "PMID:213177", "title": "Possible serotonin-agonist action of veratramine.", "content": "Veratramine produces a characteristic excitatory action on the central nervous system, producing both tremor and a characteristic \"struggling\" behavior. This behavioral excitation is accompanied by changes in serotonin content in hypothalamus. The central serotonin agonist methysergide in doses of 5--15 mg per kg produces a dose-dependent inhibition of veratramine's action, while parachlorophenylalanine has no effect. These results are consistent with a serotonin agonist mechanism to explain veratramine's action.", "contents": "Possible serotonin-agonist action of veratramine. Veratramine produces a characteristic excitatory action on the central nervous system, producing both tremor and a characteristic \"struggling\" behavior. This behavioral excitation is accompanied by changes in serotonin content in hypothalamus. The central serotonin agonist methysergide in doses of 5--15 mg per kg produces a dose-dependent inhibition of veratramine's action, while parachlorophenylalanine has no effect. These results are consistent with a serotonin agonist mechanism to explain veratramine's action."}
{"id": "PMID:213181", "title": "Abnormalities in pulmonary function after brief exposure to toxic metal fumes.", "content": "A 26-year-old welder became ill after exposure to zinc and cadmium fumes at work. His initial clinical course was consistent with that of metal fume fever, but persistence of symptoms and signs beyond the usual duration in this condition led to suspicion of a toxic pulmonary reaction to cadmium. The finding of high percentages of both metals in the urine confirmed this diagnosis. Pulmonary function tests showed restriction of lung volumes, with increased elastic recoil and reduced diffusion, but no evidence of airways obstruction. Chest roentgenograms indicated central pulmonary edema, which cleared in 6 days. Follow-up assessment 2 years later showed incomplete improvement of the restrictive ventilatory defect.", "contents": "Abnormalities in pulmonary function after brief exposure to toxic metal fumes. A 26-year-old welder became ill after exposure to zinc and cadmium fumes at work. His initial clinical course was consistent with that of metal fume fever, but persistence of symptoms and signs beyond the usual duration in this condition led to suspicion of a toxic pulmonary reaction to cadmium. The finding of high percentages of both metals in the urine confirmed this diagnosis. Pulmonary function tests showed restriction of lung volumes, with increased elastic recoil and reduced diffusion, but no evidence of airways obstruction. Chest roentgenograms indicated central pulmonary edema, which cleared in 6 days. Follow-up assessment 2 years later showed incomplete improvement of the restrictive ventilatory defect."}
{"id": "PMID:213182", "title": "Bordetella pertussis serotypes in Canada.", "content": "A study was done to determine the major antigenic factors of Bordetella pertussis strains isolated throughout Canada and whether these isolates have the same antigenic structure as the bacilli in the currently used vaccines. Testing for the major pertussis antigens, factors 1, 2 and 3, was conducted with 440 freshly isolated strains of B. pertussis received from seven canadian provinces between August 1976 and February 1978 and six batches of pertussis vaccine or immunizing agents containing pertussis vaccine. With the aid of specific antisera prepared in rabbits, the antigenic factors were detected by a slide agglutination technique. Almost all (98.9%) of the pertussis strains examined were serotype 1,3. All six batches of pertussis vaccine or immunizing agents containing pertussis vaccine proved to be rich in each of the three main pertussis agglutinogens.", "contents": "Bordetella pertussis serotypes in Canada. A study was done to determine the major antigenic factors of Bordetella pertussis strains isolated throughout Canada and whether these isolates have the same antigenic structure as the bacilli in the currently used vaccines. Testing for the major pertussis antigens, factors 1, 2 and 3, was conducted with 440 freshly isolated strains of B. pertussis received from seven canadian provinces between August 1976 and February 1978 and six batches of pertussis vaccine or immunizing agents containing pertussis vaccine. With the aid of specific antisera prepared in rabbits, the antigenic factors were detected by a slide agglutination technique. Almost all (98.9%) of the pertussis strains examined were serotype 1,3. All six batches of pertussis vaccine or immunizing agents containing pertussis vaccine proved to be rich in each of the three main pertussis agglutinogens."}
{"id": "PMID:213178", "title": "Effects of decapitation-stress on the phosphorylation of cortical membrane proteins.", "content": "The endogenous phosphorylation of membrane-bound proteins was studied in preparations from the cerebral cortex of rats sacrificed by immersion in liquid nitrogen or by decapitation. Compared to quick-frozen rats, samples from decapitated animals demonstrated a two-fold increase in 32P-phosphate incorporation into specific protein bands with apparent molecular weights of 56K, and 52K (designated E1 and E2) and a decreased incorporation into a phosphoprotein of 47K (designated F). The phosphorylation of two proteins (78K and 34K) in membranes from decapitated rats was found to be highly stimulated by exogenously added cyclic AMP. On the other hand, the phosphorylation of specific protein bands in preparations from quick frozen rats was minimally affected by addition of cyclic AMP. The results indicate that conditions which lead to increases in cyclic AMP levels in the brain in situ induce specific changes in phosphorylative activity, and these can be detected by assaying isolated membrane fragments in vitro.", "contents": "Effects of decapitation-stress on the phosphorylation of cortical membrane proteins. The endogenous phosphorylation of membrane-bound proteins was studied in preparations from the cerebral cortex of rats sacrificed by immersion in liquid nitrogen or by decapitation. Compared to quick-frozen rats, samples from decapitated animals demonstrated a two-fold increase in 32P-phosphate incorporation into specific protein bands with apparent molecular weights of 56K, and 52K (designated E1 and E2) and a decreased incorporation into a phosphoprotein of 47K (designated F). The phosphorylation of two proteins (78K and 34K) in membranes from decapitated rats was found to be highly stimulated by exogenously added cyclic AMP. On the other hand, the phosphorylation of specific protein bands in preparations from quick frozen rats was minimally affected by addition of cyclic AMP. The results indicate that conditions which lead to increases in cyclic AMP levels in the brain in situ induce specific changes in phosphorylative activity, and these can be detected by assaying isolated membrane fragments in vitro."}
{"id": "PMID:213183", "title": "The disparity of indirect and direct zirconyl-gel assays for carcinoembryonic antigen.", "content": "Experience with the zirconyl phosphate gel (Z-gel) radioimmunoassays for plasma CEA levels below 20 ng/ml (the indirect method) and for levels greater than 20 ng/ml (the direct method) has shown that a disparity of values exists, caused by shifting from one assay to the other. This disparity is at least partially due to PCA-labile proteins reacting in the direct assay. It may be constant for individual patients but varies among patients. The magnitude of this disparity is independent of the CEA level (above 15 ng/ml).", "contents": "The disparity of indirect and direct zirconyl-gel assays for carcinoembryonic antigen. Experience with the zirconyl phosphate gel (Z-gel) radioimmunoassays for plasma CEA levels below 20 ng/ml (the indirect method) and for levels greater than 20 ng/ml (the direct method) has shown that a disparity of values exists, caused by shifting from one assay to the other. This disparity is at least partially due to PCA-labile proteins reacting in the direct assay. It may be constant for individual patients but varies among patients. The magnitude of this disparity is independent of the CEA level (above 15 ng/ml)."}
{"id": "PMID:213185", "title": "Scintigraphic evaluation of sarcomata in children and adults by Ga67 citrate.", "content": "Gallium-67 scans were performed on 32 patients with adult and childhood sarcomata as part of clinical staging studies. Gallium-67 scans proved to be highly accurate in assessing sites of disease in patients with malignant schwannoma, Ewing's sarcoma, and rhabdomyosarcoma. Gallium-67 scans were inaccurate in determining sites of disease in patients with other types of sarcomata. It is concluded that Gallium-67 scanning is a useful adjunct to clinical staging in selected patients with sarcomata.", "contents": "Scintigraphic evaluation of sarcomata in children and adults by Ga67 citrate. Gallium-67 scans were performed on 32 patients with adult and childhood sarcomata as part of clinical staging studies. Gallium-67 scans proved to be highly accurate in assessing sites of disease in patients with malignant schwannoma, Ewing's sarcoma, and rhabdomyosarcoma. Gallium-67 scans were inaccurate in determining sites of disease in patients with other types of sarcomata. It is concluded that Gallium-67 scanning is a useful adjunct to clinical staging in selected patients with sarcomata."}
{"id": "PMID:213186", "title": "A stratified randomized study of intradermal BCG in patients with carcinoma of the bronchus: prolongation of quality but not length of life in inoperable patients.", "content": "This paper reports the results of a stratified, randomized trial of monthly intradermal injections of Glaxo BCG in addition to conventional therapy (surgery, radiotherapy or no treatment) in a consecutive series of 75 men with confirmed bronchial carcinoma. BCG treatment did not significantly prolong survival but had consistenly more effect in prolonging the period in good general condition and in \"acceptable\" clinical condition. These were significantly prolonged among the BCG patients (all histopathologies) treated with a full course of radiotherapy (p = 0.01, p = 0.005) and among the 43 patients with squamous carcinoma after adjustment for treatment and general prognostic factors (ratio of observed to expected deaths (O/E) for BCG 0.65, P = 0.025). There was a tendency for BCG patients with oat cell carcinoma to survive less well than controls (O/E for BCG 1.40 not significant). Within comparable groups of patients with squamous carcinoma the delay in decline of general condition was accompanied by reduced weight loss.", "contents": "A stratified randomized study of intradermal BCG in patients with carcinoma of the bronchus: prolongation of quality but not length of life in inoperable patients. This paper reports the results of a stratified, randomized trial of monthly intradermal injections of Glaxo BCG in addition to conventional therapy (surgery, radiotherapy or no treatment) in a consecutive series of 75 men with confirmed bronchial carcinoma. BCG treatment did not significantly prolong survival but had consistenly more effect in prolonging the period in good general condition and in \"acceptable\" clinical condition. These were significantly prolonged among the BCG patients (all histopathologies) treated with a full course of radiotherapy (p = 0.01, p = 0.005) and among the 43 patients with squamous carcinoma after adjustment for treatment and general prognostic factors (ratio of observed to expected deaths (O/E) for BCG 0.65, P = 0.025). There was a tendency for BCG patients with oat cell carcinoma to survive less well than controls (O/E for BCG 1.40 not significant). Within comparable groups of patients with squamous carcinoma the delay in decline of general condition was accompanied by reduced weight loss."}
{"id": "PMID:213187", "title": "Undifferentiated sarcoma of the kidney: a tumor of childhood with histopathologic and clinical characteristics distinct from Wilms' tumor.", "content": "The pathological and clinical features of 123 patients with Wilms' tumor diagnosed between 1961 and 1977 were analyzed. A subgroup of nine patients with distinctive histology characterized by the presence of exclusively sarcomatous elements was identified. These patients were indistinguishable clinically from the other patients with Wilms' tumor and were treated as Wilms' tumor. The rate of recurrence in this group of sarcomatous Wilms' tumor was very high (7/9) and long-term disease-free survival correspondingly low )3/9 free of disease from 15 months to nine years) when compared to the patients with classical Wilms' tumor (50% recurrence rate and 71% currently free of disease). In addition, patients with metastases (seven of seven patients with recurrence had skeletal involvement as contrasted to one of 50 patients with metastatic classical Wilms' tumor). We conclude that the \"sarcomatous Wilms' tumor\" represents a distinct clinicopathological entity identifiable morphologically at diagnosis, best described as renal sarcoma and that in the future optimal treatment of this disease may vary somewhat from the treatment of classical Wilms' tumor.", "contents": "Undifferentiated sarcoma of the kidney: a tumor of childhood with histopathologic and clinical characteristics distinct from Wilms' tumor. The pathological and clinical features of 123 patients with Wilms' tumor diagnosed between 1961 and 1977 were analyzed. A subgroup of nine patients with distinctive histology characterized by the presence of exclusively sarcomatous elements was identified. These patients were indistinguishable clinically from the other patients with Wilms' tumor and were treated as Wilms' tumor. The rate of recurrence in this group of sarcomatous Wilms' tumor was very high (7/9) and long-term disease-free survival correspondingly low )3/9 free of disease from 15 months to nine years) when compared to the patients with classical Wilms' tumor (50% recurrence rate and 71% currently free of disease). In addition, patients with metastases (seven of seven patients with recurrence had skeletal involvement as contrasted to one of 50 patients with metastatic classical Wilms' tumor). We conclude that the \"sarcomatous Wilms' tumor\" represents a distinct clinicopathological entity identifiable morphologically at diagnosis, best described as renal sarcoma and that in the future optimal treatment of this disease may vary somewhat from the treatment of classical Wilms' tumor."}
{"id": "PMID:213188", "title": "Bone metastasizing renal tumor of childhood: morphological and clinical features, and differences from Wilms' tumor.", "content": "A bone metastasizing primary renal tumor of childhood is described, and five cases are presented. Although all five cases were originally diagnosed as nephroblastomata, there appear to be sufficient histological, ultrastructural and clinical differences to suggest that these tumors should comprise a separate and distinct entity. Using the data from the Manchester Children's Tumor Registry, the incidence of this tumor was found to be 2.3% of all primary renal neoplasms in childhood.", "contents": "Bone metastasizing renal tumor of childhood: morphological and clinical features, and differences from Wilms' tumor. A bone metastasizing primary renal tumor of childhood is described, and five cases are presented. Although all five cases were originally diagnosed as nephroblastomata, there appear to be sufficient histological, ultrastructural and clinical differences to suggest that these tumors should comprise a separate and distinct entity. Using the data from the Manchester Children's Tumor Registry, the incidence of this tumor was found to be 2.3% of all primary renal neoplasms in childhood."}
{"id": "PMID:213189", "title": "Association of breast cancer with meningioma: report of two cases and review of the literature.", "content": "We report two cases of breast cancer in whom meningioma subsequently developed and provide a brief review of the literature. A hormonal interrelationship is suggested. The knowledge of this potential association is important in the interpretation and treatment of patients with breast cancer who develop central nervous system manifestations.", "contents": "Association of breast cancer with meningioma: report of two cases and review of the literature. We report two cases of breast cancer in whom meningioma subsequently developed and provide a brief review of the literature. A hormonal interrelationship is suggested. The knowledge of this potential association is important in the interpretation and treatment of patients with breast cancer who develop central nervous system manifestations."}
{"id": "PMID:213190", "title": "Transbronchial lung biopsy in the diagnosis of lymphangitic carcinomatosis.", "content": "The clinical diagnosis of lymphangitic carcinomatosis of the lung has generally been confirmed by open lung or transthoracic needle biopsy, precedures with significant morbidity and mortality, particularly in patients with respiratory insufficiency. We present six cases of lymphangitic carcinomatosis diagnosed by transbronchial biopsy. Autopsy confirmation was obtained in 4 patients and ultrastructural confirmation of intralymphatic location of tumor in one. The diffuse bronchial and peribronchial lymphatic involvement demonstrated here suggests that this relatively noninvasive technique should be the procedure of choice in the diagnosis of lymphangitic carcinomatosis of the lung.", "contents": "Transbronchial lung biopsy in the diagnosis of lymphangitic carcinomatosis. The clinical diagnosis of lymphangitic carcinomatosis of the lung has generally been confirmed by open lung or transthoracic needle biopsy, precedures with significant morbidity and mortality, particularly in patients with respiratory insufficiency. We present six cases of lymphangitic carcinomatosis diagnosed by transbronchial biopsy. Autopsy confirmation was obtained in 4 patients and ultrastructural confirmation of intralymphatic location of tumor in one. The diffuse bronchial and peribronchial lymphatic involvement demonstrated here suggests that this relatively noninvasive technique should be the procedure of choice in the diagnosis of lymphangitic carcinomatosis of the lung."}
{"id": "PMID:213191", "title": "Detection and significance of occult axillary node metastases in patients with invasive breast cancer.", "content": "Blocks of axillary lymph nodes from 78 patients with invasive breast cancer, which after \"routine\" pathological examination were regarded as negative for metastases, were step-sectioned at 20 u intervals. Occult metastases were detected in 24% of the cases. A significant association between such metastases and a lack of or slight degree of an intraductal carcinomatous component of the dominant cancer was noted. There was no relationship between occult metastases and 15 other histopathological and 3 clinical features investigated, including an average 5 year survival rate. Similarly there was no correlation between any of the possible discriminants investigated in the 24% of patients who have died of their diseases or are living with recurrence regardless of the presence of occult metastases. Factors accounting for the lack of universal survival in patients with Stage I (and those with occult metastases that might be designated as stage 11/2) remain enigmatic. It is concluded that attempts to detect occult metastases by extending histopathological methods may be more academic than practical or therapeutically significant.", "contents": "Detection and significance of occult axillary node metastases in patients with invasive breast cancer. Blocks of axillary lymph nodes from 78 patients with invasive breast cancer, which after \"routine\" pathological examination were regarded as negative for metastases, were step-sectioned at 20 u intervals. Occult metastases were detected in 24% of the cases. A significant association between such metastases and a lack of or slight degree of an intraductal carcinomatous component of the dominant cancer was noted. There was no relationship between occult metastases and 15 other histopathological and 3 clinical features investigated, including an average 5 year survival rate. Similarly there was no correlation between any of the possible discriminants investigated in the 24% of patients who have died of their diseases or are living with recurrence regardless of the presence of occult metastases. Factors accounting for the lack of universal survival in patients with Stage I (and those with occult metastases that might be designated as stage 11/2) remain enigmatic. It is concluded that attempts to detect occult metastases by extending histopathological methods may be more academic than practical or therapeutically significant."}
{"id": "PMID:213192", "title": "Pancytopenia induced by aminoglutethimide in the treatment of breast cancer.", "content": "Aminoglutethimide is an investigational agent of proven benefit in the treatment of metastatic breast carcinoma. We report herein a case of aminoglutethimide-induced pancytopenia complicated by bleeding and gram-negative septicemia. Severe pancytopenia is a rare but important side effect of this new drug and is rapidly reversible when the agent is withdrawn.", "contents": "Pancytopenia induced by aminoglutethimide in the treatment of breast cancer. Aminoglutethimide is an investigational agent of proven benefit in the treatment of metastatic breast carcinoma. We report herein a case of aminoglutethimide-induced pancytopenia complicated by bleeding and gram-negative septicemia. Severe pancytopenia is a rare but important side effect of this new drug and is rapidly reversible when the agent is withdrawn."}
{"id": "PMID:213193", "title": "A simple assay procedure for beta-D-mannanase.", "content": "A simple assay procedure for beta-D-mannanase enzyme has been developed which employs carob D-galacto-D-mannan dyed with Remazolbrilliant Blue. Additionally, the procedure is quantitative, relatively sensitive, and highly specific for beta-D-mannanase enzyme. It can be readily used for the determination of beta-D-mannanase activity in crude enzyme preparations and column-chromatography eluates.", "contents": "A simple assay procedure for beta-D-mannanase. A simple assay procedure for beta-D-mannanase enzyme has been developed which employs carob D-galacto-D-mannan dyed with Remazolbrilliant Blue. Additionally, the procedure is quantitative, relatively sensitive, and highly specific for beta-D-mannanase enzyme. It can be readily used for the determination of beta-D-mannanase activity in crude enzyme preparations and column-chromatography eluates."}
{"id": "PMID:213197", "title": "Comparison of transcription stimulating, phenol-soluble non-histone chromosomal proteins in normal rat liver and transplantable hepatocellular carcinomas.", "content": "The non-histone chromosomal proteins (NHCP) of a rapidly and slowly proliferating transplantable hepatocellular carcinoma (THC) were compared to those of normal and regenerating rat liver. The total quantity of NHCP is approximately threefold higher in the THCs than in either normal rat liver at 4 h and 44 h regenerating rat liver. Only those NHCP that can be extracted from chromatin by 0.35 M NaCl were further examined and it was observed that the proteins of this highly complex fraction could be further fractionated by their differential phenol-solubility. The phenol-soluble 0.35 NHCP contained protein(s) capable of stimulating the level of DNA-directed RNA synthesis in vitro. The total amount of this stimulatory activity was 5 times higher in the rapidly growing THC and 1.6 times higher in the slowly growing THC than in normal rat liver. In order to assess the contribution of cell-cycle dependent alterations on the increase in the amount of stimulatory activity in the THCs, 44 h regenerating rat livers were examined. This tissue represents a mix of cells in various stages of the cell cycle which is similar to that found in the THCs. It was found that the total quantity of NHCP in the 44 h regenerating rat liver was the same as in normal rat liver. The total amount of the stimulatory activity also was similar in both the normal and 44 h regenerating rat liver. The amount of the stimulatory activity was found to double in 4 h regenerating rat liver, however. These data suggest that the alterations observed in the NHCP of the THCs are not due solely to cell cycle dependent changes, but may represent malignancy dependent alterations.", "contents": "Comparison of transcription stimulating, phenol-soluble non-histone chromosomal proteins in normal rat liver and transplantable hepatocellular carcinomas. The non-histone chromosomal proteins (NHCP) of a rapidly and slowly proliferating transplantable hepatocellular carcinoma (THC) were compared to those of normal and regenerating rat liver. The total quantity of NHCP is approximately threefold higher in the THCs than in either normal rat liver at 4 h and 44 h regenerating rat liver. Only those NHCP that can be extracted from chromatin by 0.35 M NaCl were further examined and it was observed that the proteins of this highly complex fraction could be further fractionated by their differential phenol-solubility. The phenol-soluble 0.35 NHCP contained protein(s) capable of stimulating the level of DNA-directed RNA synthesis in vitro. The total amount of this stimulatory activity was 5 times higher in the rapidly growing THC and 1.6 times higher in the slowly growing THC than in normal rat liver. In order to assess the contribution of cell-cycle dependent alterations on the increase in the amount of stimulatory activity in the THCs, 44 h regenerating rat livers were examined. This tissue represents a mix of cells in various stages of the cell cycle which is similar to that found in the THCs. It was found that the total quantity of NHCP in the 44 h regenerating rat liver was the same as in normal rat liver. The total amount of the stimulatory activity also was similar in both the normal and 44 h regenerating rat liver. The amount of the stimulatory activity was found to double in 4 h regenerating rat liver, however. These data suggest that the alterations observed in the NHCP of the THCs are not due solely to cell cycle dependent changes, but may represent malignancy dependent alterations."}
{"id": "PMID:213200", "title": "Gestational changes in pulmonary converting enzyme activity in the fetal rabbit.", "content": "Changes in angiotensin-converting enzyme were measured in the lungs of fetal rabbits isolated and perfused in situ at varying ages from 22 days gestation to 7 days of age under controlled conditions of flow, pH, and temperature. Enzyme activity was assessed by infusing bradykinin or angiotensin I in Krebs-Henseleit solution and measuring residual peptide in the effluent by radioimmunoassay. The levels of substrate studied were below those required for enzyme saturation. Lungs of 22 day gestation fetuses removed only one-third of either peptide. The activity at term and in neonatal life resulted in more than 80% peptide removal. The time of the greatest rise in the percent substrate cleared occurs earlier than the time of the greatest increase in lung and body weight. The lower percentage of substrate cleared in early gestation appears to result in part from a limited surface area for enzyme activity in the primitive fetal pulmonary microvascular bed, since morphological studies with fluorescein-tagged anticonverting enzyme antibody demonstrated the presence of enzyme in the lung as early as 17 days of gestation. Electron micrographs of the pulmonary endothelial cell surface reveal that the degree of surface infolding and hence surface area increases with gestation. The higher percentage of substrate cleared in later gestation closely parallels the structural and ultrastructural development of the vascular bed. The presence of converting enzyme in the placenta by the second third of gestation and the large size of the placenta suggest that this organ may be a major locus of converting enzyme activity in the fetus.", "contents": "Gestational changes in pulmonary converting enzyme activity in the fetal rabbit. Changes in angiotensin-converting enzyme were measured in the lungs of fetal rabbits isolated and perfused in situ at varying ages from 22 days gestation to 7 days of age under controlled conditions of flow, pH, and temperature. Enzyme activity was assessed by infusing bradykinin or angiotensin I in Krebs-Henseleit solution and measuring residual peptide in the effluent by radioimmunoassay. The levels of substrate studied were below those required for enzyme saturation. Lungs of 22 day gestation fetuses removed only one-third of either peptide. The activity at term and in neonatal life resulted in more than 80% peptide removal. The time of the greatest rise in the percent substrate cleared occurs earlier than the time of the greatest increase in lung and body weight. The lower percentage of substrate cleared in early gestation appears to result in part from a limited surface area for enzyme activity in the primitive fetal pulmonary microvascular bed, since morphological studies with fluorescein-tagged anticonverting enzyme antibody demonstrated the presence of enzyme in the lung as early as 17 days of gestation. Electron micrographs of the pulmonary endothelial cell surface reveal that the degree of surface infolding and hence surface area increases with gestation. The higher percentage of substrate cleared in later gestation closely parallels the structural and ultrastructural development of the vascular bed. The presence of converting enzyme in the placenta by the second third of gestation and the large size of the placenta suggest that this organ may be a major locus of converting enzyme activity in the fetus."}
{"id": "PMID:213201", "title": "Alpha-adrenergic receptors in rat myocardium. Identification by binding of [3H]dihydroergocryptine.", "content": "[3H]Dihydroergocryptine ([3H]DHE) binds to sites in membranes derived from rat myocardium that have the characteristics expected of alpha-adrenergic receptors. The binding is saturable with 41 fmol [3H]DHE bound per mg of protein and of high affinity with KD = 2.9 nM. The binding is rapid and readily reversible. Adrenergic agonists compete with [3H]DHE for binding in the order: epinephrine greater than norepinephrine greater than isoproterenol; and adrenergic antagonists compete for binding in the order: phentolamine greater than propranolol. For comparison, (-)[3H]dihydroalprenolol [(-)[3h]dha] was used to bind to sites in the same membrane preparations having characteristics of beta-receptors. The number and affinity of beta-receptors were quite similar to those of the alpha-receptors with 46 fmol (-)[EH]DHA per mg protein bound at saturation and KD = 2.5 nM. These techniques allowed identification of both beta- and alpha-adrenergic receptors in membranes derived from isolated atria, right ventricular free walls, and left ventricles including interventricular septa. This is the first report documenting direct identification of myocardial alpha-receptors by radioligand-binding techniques and complements the literature previously reporting myocardial inotopic and electrophysiological responses to alpha-adrenergic stimulation.", "contents": "Alpha-adrenergic receptors in rat myocardium. Identification by binding of [3H]dihydroergocryptine. [3H]Dihydroergocryptine ([3H]DHE) binds to sites in membranes derived from rat myocardium that have the characteristics expected of alpha-adrenergic receptors. The binding is saturable with 41 fmol [3H]DHE bound per mg of protein and of high affinity with KD = 2.9 nM. The binding is rapid and readily reversible. Adrenergic agonists compete with [3H]DHE for binding in the order: epinephrine greater than norepinephrine greater than isoproterenol; and adrenergic antagonists compete for binding in the order: phentolamine greater than propranolol. For comparison, (-)[3H]dihydroalprenolol [(-)[3h]dha] was used to bind to sites in the same membrane preparations having characteristics of beta-receptors. The number and affinity of beta-receptors were quite similar to those of the alpha-receptors with 46 fmol (-)[EH]DHA per mg protein bound at saturation and KD = 2.5 nM. These techniques allowed identification of both beta- and alpha-adrenergic receptors in membranes derived from isolated atria, right ventricular free walls, and left ventricles including interventricular septa. This is the first report documenting direct identification of myocardial alpha-receptors by radioligand-binding techniques and complements the literature previously reporting myocardial inotopic and electrophysiological responses to alpha-adrenergic stimulation."}
{"id": "PMID:213202", "title": "Effects of well-defined ischemia on myocardial lysosomal and microsomal enzymes in a canine model.", "content": "We have used a new technique for extraction of myocardial membranes (0.25 M sucrose, 0.6 M KCl) to isolate particulate and soluble proteins and enzymatic activities in an effort to quantify changes characteristic of progressive ischemia. Myocardial blood flow (MBF) was measured with microspheres (15 micrometer diameter) in all samples of tissue used for assay of proteins and enzymatic activities; MBF to the moderately ischemic areas (M-ischemia) was 53% of control (H-control); MBF to the severely ischemic areas (L-ischemia) was 9% of control. Significant decreases (P less than 0.001) in content of protein were seen in all post 1,000 g pellets and supernatant fluids in the L-ischemia zones; particulate lysosomal enzymatic activity was significantly decreased (P less than 0.001) in all four post 1,000 g pellets (2,500 g to 140,000 g) of the L-ischemic areas (for N-acetyl-beta-glucosaminidase and beta-glucuronidase). The increase in percent free activity of lysosomal enzymes (index of loss of latency) also was highly significant (P less than 0.001) in all particulate fractions of the L-ischemic areas. In addition, about 45% of the total activity of the microsomal marker enzyme, rotenone-insensitive NADH cytochrome C reductase (RINCR), was found in the 140,000 g pellet of H-control tissue (9.9 micronmol/min per g); this activity fell to 8.1 micronmol/min per g in M-ischemic areas (P less than 0.001) and to 5.3 micronmol/min per g in L-ischemic areas (P less than 0.001). This study demonstrates that changes in myocardial proteins, lysosomes, and other membrane-bound enzymes (RINCR) may provide reproducible bichemical parameters for assessing ischemic myocardial injury.", "contents": "Effects of well-defined ischemia on myocardial lysosomal and microsomal enzymes in a canine model. We have used a new technique for extraction of myocardial membranes (0.25 M sucrose, 0.6 M KCl) to isolate particulate and soluble proteins and enzymatic activities in an effort to quantify changes characteristic of progressive ischemia. Myocardial blood flow (MBF) was measured with microspheres (15 micrometer diameter) in all samples of tissue used for assay of proteins and enzymatic activities; MBF to the moderately ischemic areas (M-ischemia) was 53% of control (H-control); MBF to the severely ischemic areas (L-ischemia) was 9% of control. Significant decreases (P less than 0.001) in content of protein were seen in all post 1,000 g pellets and supernatant fluids in the L-ischemia zones; particulate lysosomal enzymatic activity was significantly decreased (P less than 0.001) in all four post 1,000 g pellets (2,500 g to 140,000 g) of the L-ischemic areas (for N-acetyl-beta-glucosaminidase and beta-glucuronidase). The increase in percent free activity of lysosomal enzymes (index of loss of latency) also was highly significant (P less than 0.001) in all particulate fractions of the L-ischemic areas. In addition, about 45% of the total activity of the microsomal marker enzyme, rotenone-insensitive NADH cytochrome C reductase (RINCR), was found in the 140,000 g pellet of H-control tissue (9.9 micronmol/min per g); this activity fell to 8.1 micronmol/min per g in M-ischemic areas (P less than 0.001) and to 5.3 micronmol/min per g in L-ischemic areas (P less than 0.001). This study demonstrates that changes in myocardial proteins, lysosomes, and other membrane-bound enzymes (RINCR) may provide reproducible bichemical parameters for assessing ischemic myocardial injury."}
{"id": "PMID:213203", "title": "Lack of effect of methylprednisolone on lysosomal and microsomal enzymes after two hours of well-defined canine myocardial ischemia.", "content": "Myocardial ischemia was produced for 2 hours by coronary ligation in 11 dogs pretreated with methylprednisolone (MP, 30 mg/kg). Myocardial blood flow (MBF) was measured with microspheres (15 micrometer) in each tissue sample used for enzymatic analysis. Homogenates of these tissue samples were separated by ultracentrifugation into lysosome-rich and microsomal fractions and were analyzed for N-acetyl-beta-glusosaminidase (NAGA), beta-glucuronidase (beta-gluc), rotenone-insensitive-NADH-cytochrome c reductase (RINCR), and cytochrome oxidase. The enzymatic data from centrifugal fractions were grouped according to MBF values for statistical analysis of inter-group effects of ischemia. Significant losses (P less than 0.001) of NAGA and beta-gluc were seen in all MP-treated lysosome-rich particulate fractions that were isolated from zones demonstrating MBF values less than 25% of control (L-ischemia). Similar significant losses (P less than 0.001) of RINCR were seen in microsomal fractions from L-ischemia zones. Samples with MBF values greater than 25% but less than 75% of control (M-ischemia) also demonstrated significant decreases of lysosomal and microsomal enzymatic activity in specific fractions. When the data of the above MP-treated group were compared with the untreated control group, no significant intergroup effects of treatment with MP were observed. In addition, enzymatic data (NAGA, RINCR) were normalized prior to performing linear regression analyses; percent loss of particulate enzymatic activity was plotted against percent decrease in MBF. The effects of 2 hours of ischemia on the above biochemical parameters were comparable between untreated and MP-treated groups. Finally, when myocardial samples were grouped according to similar levels of MBF, statistical analysis using the general linear models procedure revealed no beneficial effect of MP treatment on changes in lysosomal hydrolases, microsomal RINCR, or latency of lysosomes.", "contents": "Lack of effect of methylprednisolone on lysosomal and microsomal enzymes after two hours of well-defined canine myocardial ischemia. Myocardial ischemia was produced for 2 hours by coronary ligation in 11 dogs pretreated with methylprednisolone (MP, 30 mg/kg). Myocardial blood flow (MBF) was measured with microspheres (15 micrometer) in each tissue sample used for enzymatic analysis. Homogenates of these tissue samples were separated by ultracentrifugation into lysosome-rich and microsomal fractions and were analyzed for N-acetyl-beta-glusosaminidase (NAGA), beta-glucuronidase (beta-gluc), rotenone-insensitive-NADH-cytochrome c reductase (RINCR), and cytochrome oxidase. The enzymatic data from centrifugal fractions were grouped according to MBF values for statistical analysis of inter-group effects of ischemia. Significant losses (P less than 0.001) of NAGA and beta-gluc were seen in all MP-treated lysosome-rich particulate fractions that were isolated from zones demonstrating MBF values less than 25% of control (L-ischemia). Similar significant losses (P less than 0.001) of RINCR were seen in microsomal fractions from L-ischemia zones. Samples with MBF values greater than 25% but less than 75% of control (M-ischemia) also demonstrated significant decreases of lysosomal and microsomal enzymatic activity in specific fractions. When the data of the above MP-treated group were compared with the untreated control group, no significant intergroup effects of treatment with MP were observed. In addition, enzymatic data (NAGA, RINCR) were normalized prior to performing linear regression analyses; percent loss of particulate enzymatic activity was plotted against percent decrease in MBF. The effects of 2 hours of ischemia on the above biochemical parameters were comparable between untreated and MP-treated groups. Finally, when myocardial samples were grouped according to similar levels of MBF, statistical analysis using the general linear models procedure revealed no beneficial effect of MP treatment on changes in lysosomal hydrolases, microsomal RINCR, or latency of lysosomes."}
{"id": "PMID:213205", "title": "Segmental alpha-receptor-mediated vasoconstriction in the canine coronary circulation.", "content": "Recent studies from this laboratory have indicated that sympathetic alpha-receptor-mediated coronary vasoconstriction can compete with local metabolic vasodilation to reduce the oxygen supply to the myocardium. In vitro studies from other laboratories on isolated coronary vessel strips suggest that large epicardial vessels are the dominant site of adrenergic alpha-receptor activity. In this study we used anesthetized, open-chest dogs to test the hypothesis that alpha-receptor-mediated vasoconstriction occurs predominantly in epicardial vessels, which are partially removed from the metabolic milieu in the myocardium. Adrenergic beta-receptor blockade was achieved by propranolol (3 mg/kg, iv). The circumflex coronary artery was pump-perfused at constant pressure to minimize passive changes in large vessel resistance. Pressure was measured at the tip of the perfusion cannula sealed in the circumflex artery, and in an apical branch of the circumflex artery. Large vessel resistance was calculated as the pressure gradient along the vessel segment divided by the coronary flow. Intracoronary injections of nitroglycerin were used as an independent measure of the vasomotor responsiveness of the large vessel segment. Adrenergic alpha-receptor activation was produced by intracoronary bolus injections of norepinephrine and by electrical stimulation of the left stellate ganglion. Alpha-receptor stimulation caused an increase in total coronary vascular resistance; however, the relative increase in the resistance of the large vessel was only about 60% of that seen for the entire coronary bed. These data suggest that, contrary to the proposed hypothesis, adrenergic alpha-receptor-mediated vasoconstriction in the large coronary vessels is not proportionally greater than that observed in the total coronary vascular bed.", "contents": "Segmental alpha-receptor-mediated vasoconstriction in the canine coronary circulation. Recent studies from this laboratory have indicated that sympathetic alpha-receptor-mediated coronary vasoconstriction can compete with local metabolic vasodilation to reduce the oxygen supply to the myocardium. In vitro studies from other laboratories on isolated coronary vessel strips suggest that large epicardial vessels are the dominant site of adrenergic alpha-receptor activity. In this study we used anesthetized, open-chest dogs to test the hypothesis that alpha-receptor-mediated vasoconstriction occurs predominantly in epicardial vessels, which are partially removed from the metabolic milieu in the myocardium. Adrenergic beta-receptor blockade was achieved by propranolol (3 mg/kg, iv). The circumflex coronary artery was pump-perfused at constant pressure to minimize passive changes in large vessel resistance. Pressure was measured at the tip of the perfusion cannula sealed in the circumflex artery, and in an apical branch of the circumflex artery. Large vessel resistance was calculated as the pressure gradient along the vessel segment divided by the coronary flow. Intracoronary injections of nitroglycerin were used as an independent measure of the vasomotor responsiveness of the large vessel segment. Adrenergic alpha-receptor activation was produced by intracoronary bolus injections of norepinephrine and by electrical stimulation of the left stellate ganglion. Alpha-receptor stimulation caused an increase in total coronary vascular resistance; however, the relative increase in the resistance of the large vessel was only about 60% of that seen for the entire coronary bed. These data suggest that, contrary to the proposed hypothesis, adrenergic alpha-receptor-mediated vasoconstriction in the large coronary vessels is not proportionally greater than that observed in the total coronary vascular bed."}
{"id": "PMID:213206", "title": "Aspartate aminotransferase activity and isoenzyme proportions in human liver tissues.", "content": "Aspartate aminotransferase (EC 2.6.1.1) activity and the distribution of its isoenzymes in human liver were examined. Rabbit antiserum against porcin soluble (i.e., non-mitochondrial) enzyme cross-reacted with the soluble enzyme of human origin and was used in an immunoprecipitation assay to quantitate the soluble and mitochondrial isoenzymes. These were separated by rapid, semiquantitative electrophoresis on cellulose acetate and by three other quantitative techniques: isoelectric focusing and anion-and cation-exchange chromatography. The mitochrondrial enzyme averaged 81% of the total activity in normal adult human liver (n = 4). Its contribution was dramatically reduced in single specimens of human fetal liver (56% of total activity) and hepatoblastoma tissue  (38%). Total enzyme activities (mumol min-1 per gram of tissue) were: adult, 150; fetal, 38; tumor, 6. Total enzyme concentrations (micromoles of enzyme per kilogram of tissue) found were: adult, 10.8; fetal, 2.7; tumor, 0.4. The concentrations and isoenzyme distribution in human liver are compared to those in various animal model systems. Other methods for quantitative estimation of the isoenzymes and their adaptability for use in estimating concentrations in serum are reviewed.", "contents": "Aspartate aminotransferase activity and isoenzyme proportions in human liver tissues. Aspartate aminotransferase (EC 2.6.1.1) activity and the distribution of its isoenzymes in human liver were examined. Rabbit antiserum against porcin soluble (i.e., non-mitochondrial) enzyme cross-reacted with the soluble enzyme of human origin and was used in an immunoprecipitation assay to quantitate the soluble and mitochondrial isoenzymes. These were separated by rapid, semiquantitative electrophoresis on cellulose acetate and by three other quantitative techniques: isoelectric focusing and anion-and cation-exchange chromatography. The mitochrondrial enzyme averaged 81% of the total activity in normal adult human liver (n = 4). Its contribution was dramatically reduced in single specimens of human fetal liver (56% of total activity) and hepatoblastoma tissue  (38%). Total enzyme activities (mumol min-1 per gram of tissue) were: adult, 150; fetal, 38; tumor, 6. Total enzyme concentrations (micromoles of enzyme per kilogram of tissue) found were: adult, 10.8; fetal, 2.7; tumor, 0.4. The concentrations and isoenzyme distribution in human liver are compared to those in various animal model systems. Other methods for quantitative estimation of the isoenzymes and their adaptability for use in estimating concentrations in serum are reviewed."}
{"id": "PMID:213211", "title": "Thyroxine binding and deiodination of thyroxine by human lymphocytes.", "content": "Binding and deiodination of T4 by lymphocytes from euthyroid, hypothyroid and hyperthyroid subjects were studied. Two sets of binding sites were found on normal lymphocytes. One set with equilibrium association constant of 6.9 X 10(9) l/mol and a maximal binding capacity of 3000 mol T4 per lymphocyte, and another set with equilibrium association constant of 4.1 X 10(6) l/mol and a maximal binding capacity of 7.8 X 10(6) mol T4 per lymphocyte. The major part of the binding sites were non specific and the binding reversible. Debinding assays revealed also two types of binding site and indicated that deiodination took place predominately from one type of binding site. Deiodination assay showed that the deiodination process had a maximal deiodination capacity of 6 X 10(-13) mol T4/10(6) lymphocytes. Paper chromatography revealed only I and T4 after incubation of lymphocytes with T4. In comparing the patient groups with the control group, lymphocytes from hyperthyroids and hypothyroids exerted a higher T4 turnover (deiodinated T4/bound T4) although the difference was not statistically significant. Lymphocytes exerted a high T4 turnover at low temperature (3 degrees C) and propylthiouracil inhibited deiodination of T4 but not binding.", "contents": "Thyroxine binding and deiodination of thyroxine by human lymphocytes. Binding and deiodination of T4 by lymphocytes from euthyroid, hypothyroid and hyperthyroid subjects were studied. Two sets of binding sites were found on normal lymphocytes. One set with equilibrium association constant of 6.9 X 10(9) l/mol and a maximal binding capacity of 3000 mol T4 per lymphocyte, and another set with equilibrium association constant of 4.1 X 10(6) l/mol and a maximal binding capacity of 7.8 X 10(6) mol T4 per lymphocyte. The major part of the binding sites were non specific and the binding reversible. Debinding assays revealed also two types of binding site and indicated that deiodination took place predominately from one type of binding site. Deiodination assay showed that the deiodination process had a maximal deiodination capacity of 6 X 10(-13) mol T4/10(6) lymphocytes. Paper chromatography revealed only I and T4 after incubation of lymphocytes with T4. In comparing the patient groups with the control group, lymphocytes from hyperthyroids and hypothyroids exerted a higher T4 turnover (deiodinated T4/bound T4) although the difference was not statistically significant. Lymphocytes exerted a high T4 turnover at low temperature (3 degrees C) and propylthiouracil inhibited deiodination of T4 but not binding."}
{"id": "PMID:213212", "title": "An assay method for the measurement of urinary inhibitors of calcium phosphate formation.", "content": "An assay method has been developed for studying quantitatively the formation of calcium phosphate. The method will detect both substances which affect the solubility of calcium phosphate and substances which affect the crystal growth of the material. It is sensitive as or more sensitive than other methods described in the literature for detecting such compounds.", "contents": "An assay method for the measurement of urinary inhibitors of calcium phosphate formation. An assay method has been developed for studying quantitatively the formation of calcium phosphate. The method will detect both substances which affect the solubility of calcium phosphate and substances which affect the crystal growth of the material. It is sensitive as or more sensitive than other methods described in the literature for detecting such compounds."}
{"id": "PMID:213213", "title": "Isolation and identification of some urinary inhibitors of calcium phosphate formation.", "content": "Normal urine has been examined for substances which inhibit formation of calcium phosphate. A separation scheme involving ultrafiltration, precipitation, electrophoresis and paper chromatography was devised to isolate these substances. Contrary to what has been suggested in the literature for many years, the urines examined did not contain a potent unidentified inhibitor. The major anionic inhibitors were citric acid, pyrophosphate and isocitric acid. These substances together with a small contribution from the cations appeared to account for most, if not all, of the inhibitory activity of urine.", "contents": "Isolation and identification of some urinary inhibitors of calcium phosphate formation. Normal urine has been examined for substances which inhibit formation of calcium phosphate. A separation scheme involving ultrafiltration, precipitation, electrophoresis and paper chromatography was devised to isolate these substances. Contrary to what has been suggested in the literature for many years, the urines examined did not contain a potent unidentified inhibitor. The major anionic inhibitors were citric acid, pyrophosphate and isocitric acid. These substances together with a small contribution from the cations appeared to account for most, if not all, of the inhibitory activity of urine."}
{"id": "PMID:213214", "title": "Kasahara-variant alkaline phosphatase in a renal cell carcinoma.", "content": "Electrophoretically Kasahara-variant alkaline phosphatase we found in a renal cell carcinoma tissue. This enzyme electrophoresed more quickly than liver alkaline phosphatase but more slowly than Kasahara isoenzyme. Neuraminidase treatment of the enzyme caused retardation of electrophoretic mobility which was the same as that of neuraminidase-treated Kasahara isoenzyme. The enzymic properties of this variant enzyme such as inhibition by L-phenylalanine, L-homoarginine, L-leucine, EDTA and urea are consistent with those of Kasahara isoenzyme. On Ouchterlony double diffusion, the precipitin lines of Kasahara and Kasahara-variant enzymes produced by antibody to Kasahara isoenzyme fused completely. These facts may mean that Kasahara-variant isoenzyme is different from the Kasahara one in terminal sialic acid content.", "contents": "Kasahara-variant alkaline phosphatase in a renal cell carcinoma. Electrophoretically Kasahara-variant alkaline phosphatase we found in a renal cell carcinoma tissue. This enzyme electrophoresed more quickly than liver alkaline phosphatase but more slowly than Kasahara isoenzyme. Neuraminidase treatment of the enzyme caused retardation of electrophoretic mobility which was the same as that of neuraminidase-treated Kasahara isoenzyme. The enzymic properties of this variant enzyme such as inhibition by L-phenylalanine, L-homoarginine, L-leucine, EDTA and urea are consistent with those of Kasahara isoenzyme. On Ouchterlony double diffusion, the precipitin lines of Kasahara and Kasahara-variant enzymes produced by antibody to Kasahara isoenzyme fused completely. These facts may mean that Kasahara-variant isoenzyme is different from the Kasahara one in terminal sialic acid content."}
{"id": "PMID:213215", "title": "Acid glycosidase and arylsulfatase activities of human cerebrospinal fluid as measured by concanavalin A-sepharose affinity chromatography.", "content": "An affinity chromatographic method using concanavalin A-Sepharose is described for the determination of N-acetyl-beta-D-glucosaminidase, arylsulfatase. alpha-L-Fucosidase and alpha-D-mannosidase activities in the human cerebrospinal fluid. By this method (starting with 12 to 20 ml samples of cerebrospinal fluid) the above enzymes could be obtained in a concentrated form and their activities could be determined within incubation periods of 30 min to 1 h under the assay conditions described. The pH optima of the enzymes were in the range of pH 4 to 5. About 80% of the total cerebrospinal fluid N-acetyl-beta-D-glucosaminidase was found to be the A form by DEAE-Sephadex A-50 chromatography. About 60% of the total arylsulfatase was also found to be the A form. Determination of these enzyme activities in a few samples of human cerebrospinal fluid indicated a rough proportionality between the enzyme activities and the protein concentration in the cerebrospinal fluid.", "contents": "Acid glycosidase and arylsulfatase activities of human cerebrospinal fluid as measured by concanavalin A-sepharose affinity chromatography. An affinity chromatographic method using concanavalin A-Sepharose is described for the determination of N-acetyl-beta-D-glucosaminidase, arylsulfatase. alpha-L-Fucosidase and alpha-D-mannosidase activities in the human cerebrospinal fluid. By this method (starting with 12 to 20 ml samples of cerebrospinal fluid) the above enzymes could be obtained in a concentrated form and their activities could be determined within incubation periods of 30 min to 1 h under the assay conditions described. The pH optima of the enzymes were in the range of pH 4 to 5. About 80% of the total cerebrospinal fluid N-acetyl-beta-D-glucosaminidase was found to be the A form by DEAE-Sephadex A-50 chromatography. About 60% of the total arylsulfatase was also found to be the A form. Determination of these enzyme activities in a few samples of human cerebrospinal fluid indicated a rough proportionality between the enzyme activities and the protein concentration in the cerebrospinal fluid."}
{"id": "PMID:213218", "title": "Unilateral adrenalectomy and pituitary irradiation in the treatment of ACTH-dependent Cushing's disease in children and adolescents.", "content": "In four juvenile patients with Cushing's disease, the therapeutic approach used was unilateral adrenalectomy followed by irradiation of the pituitary. The follow-up time of these patients has ranged from 1.5 to 10 years. All four are clinically well. Concentrations of adrenal steroids are within normal limits and they require no additional medication. It is felt that this method gives young patients the chance for normal growth and pubertal development as well as a normal social life, so important in the stressful adolescent years, thus avoiding the handicap incurred by bilateral adrenalectomy and the consequent requirement for continuous substitution therapy.", "contents": "Unilateral adrenalectomy and pituitary irradiation in the treatment of ACTH-dependent Cushing's disease in children and adolescents. In four juvenile patients with Cushing's disease, the therapeutic approach used was unilateral adrenalectomy followed by irradiation of the pituitary. The follow-up time of these patients has ranged from 1.5 to 10 years. All four are clinically well. Concentrations of adrenal steroids are within normal limits and they require no additional medication. It is felt that this method gives young patients the chance for normal growth and pubertal development as well as a normal social life, so important in the stressful adolescent years, thus avoiding the handicap incurred by bilateral adrenalectomy and the consequent requirement for continuous substitution therapy."}
{"id": "PMID:213219", "title": "Augmentation of the in vitro mitogenic response of owl monkey peripheral blood lymphocytes by levamisole and loss of this effect with the development of herpesvirus saimiri-induced lymphoma.", "content": "Levamisole (LMS) has been shown to be capable of enhancing the proliferative response of normal owl monkey peripheral blood lymphocytes (PBL) to PHA, and, to a lesser degree, of increasing the level of spontaneous DNA synthesis. With the development of herpesvirus saimiri-induced lymphoma, these stimulatory responses were lost. LMS was not capable of stimulating tumour cells to normal functions, or of reversing the disease-induced suppressed functions on normal cells.", "contents": "Augmentation of the in vitro mitogenic response of owl monkey peripheral blood lymphocytes by levamisole and loss of this effect with the development of herpesvirus saimiri-induced lymphoma. Levamisole (LMS) has been shown to be capable of enhancing the proliferative response of normal owl monkey peripheral blood lymphocytes (PBL) to PHA, and, to a lesser degree, of increasing the level of spontaneous DNA synthesis. With the development of herpesvirus saimiri-induced lymphoma, these stimulatory responses were lost. LMS was not capable of stimulating tumour cells to normal functions, or of reversing the disease-induced suppressed functions on normal cells."}
{"id": "PMID:213222", "title": "Localization of 99m Tc-pyrophosphate in an islet cell tumor of the pancreas.", "content": "A case of 99m Tc-pyrophosphate uptake in an islet cell tumor of the pancreas is presented. A possible relationship of pyrophosphate uptake in this tumor with uptake in other neuroectodermal tumors which are of neural crest origin is considered.", "contents": "Localization of 99m Tc-pyrophosphate in an islet cell tumor of the pancreas. A case of 99m Tc-pyrophosphate uptake in an islet cell tumor of the pancreas is presented. A possible relationship of pyrophosphate uptake in this tumor with uptake in other neuroectodermal tumors which are of neural crest origin is considered."}
{"id": "PMID:213226", "title": "Role of tissue culture in prediction of malignancy.", "content": "It is now clear that tissue culture has a role to play in the prediction of the degree of malignancy of human brain tumors. The fact that virtually all human brain tumors grow at least for some interval in culture allows application of tissue culture to the study of all tumors. This almost universal culturability of tumors is truly a singular virtue of intracranial neoplasms. No other human solid tumor group has been so amenable to in vitro growth or study. Up to the present time, despite our experience with over 1100 human brain tumor cultures, we have been extremely conservative in altering patient management on the basis of in vitro data. As is now apparent, the basis for direct input into the clinical milieu exists and it is necessary to work on a patient by patient basis to see how well the existing criteria can be applied to help guide management. Indeed the emphasis given to tissue culture by Rubinstein already confirms the current interest in the applicability of tissue culture data to neuropathological study of tumors (48). Clearly for certain tumors which tend to be benign, tissue culture can serve to alert the clinician to the perhaps unexpected malignant potential of the lesion. For the malignant tumors, the degree of malignancy, the probable biological behavior, the role of host defense factors and therapeutic agents can all be more quantitatively defined for the individual patient by the detailed study of the patient's cultured cells. With improvement in the surgical treatment of benign tumors and with better chemotherapeutic and radiotherapeutic measures for malignant neoplasms this more detailed and precise characterization of tumor behavior has become increasingly relevant to the optimization of the clinical management of the brain tumor patient.", "contents": "Role of tissue culture in prediction of malignancy. It is now clear that tissue culture has a role to play in the prediction of the degree of malignancy of human brain tumors. The fact that virtually all human brain tumors grow at least for some interval in culture allows application of tissue culture to the study of all tumors. This almost universal culturability of tumors is truly a singular virtue of intracranial neoplasms. No other human solid tumor group has been so amenable to in vitro growth or study. Up to the present time, despite our experience with over 1100 human brain tumor cultures, we have been extremely conservative in altering patient management on the basis of in vitro data. As is now apparent, the basis for direct input into the clinical milieu exists and it is necessary to work on a patient by patient basis to see how well the existing criteria can be applied to help guide management. Indeed the emphasis given to tissue culture by Rubinstein already confirms the current interest in the applicability of tissue culture data to neuropathological study of tumors (48). Clearly for certain tumors which tend to be benign, tissue culture can serve to alert the clinician to the perhaps unexpected malignant potential of the lesion. For the malignant tumors, the degree of malignancy, the probable biological behavior, the role of host defense factors and therapeutic agents can all be more quantitatively defined for the individual patient by the detailed study of the patient's cultured cells. With improvement in the surgical treatment of benign tumors and with better chemotherapeutic and radiotherapeutic measures for malignant neoplasms this more detailed and precise characterization of tumor behavior has become increasingly relevant to the optimization of the clinical management of the brain tumor patient."}
{"id": "PMID:213231", "title": "A study in vitro of the sodium pump in fulminant hepatic failure.", "content": "1. The mechanism underlying the raised leucocyte sodium content in fulminant hepatic failure was studied by measurement of sodium fluxes, (Na+ + K+)-dependent adenosine triphosphatase activity, and leucocyte ATP content. 2. The rate constant for sodium efflux in the leucocytes was significantly reduced, and attributable to reduced activity of the enzyme (Na+ + K+)-ATPase. Leucocyte ATP content was not significantly different from that of control cells. 3. Incubation of cells from patients in the sera of normal subjects resulted in a reversal of these changes. Inhibition of the leucocyte sodium efflux rate constants and (Na+ +K+)-ATPase of normal cells was achieved by incubation in sera from patients. 4. We suggest that the raised sodium content of leucocytes in fulminant hepatic failure is attributable to a defective sodium pumping mechanism, possibly due to a circulating toxin.", "contents": "A study in vitro of the sodium pump in fulminant hepatic failure. 1. The mechanism underlying the raised leucocyte sodium content in fulminant hepatic failure was studied by measurement of sodium fluxes, (Na+ + K+)-dependent adenosine triphosphatase activity, and leucocyte ATP content. 2. The rate constant for sodium efflux in the leucocytes was significantly reduced, and attributable to reduced activity of the enzyme (Na+ + K+)-ATPase. Leucocyte ATP content was not significantly different from that of control cells. 3. Incubation of cells from patients in the sera of normal subjects resulted in a reversal of these changes. Inhibition of the leucocyte sodium efflux rate constants and (Na+ +K+)-ATPase of normal cells was achieved by incubation in sera from patients. 4. We suggest that the raised sodium content of leucocytes in fulminant hepatic failure is attributable to a defective sodium pumping mechanism, possibly due to a circulating toxin."}
{"id": "PMID:213233", "title": "Commitment to community mental health aftercare services: staffing and structural implications.", "content": "This study examines the views of community mental health practitioners toward aftercare services and deinstitutionalized patients. A survey of 361 practitioners in Allegheny County, Pennsylvania, finds that these views are related to practitioner experience in psychotherapeutic practice, professional affiliation, educational level, and amount of specialization in aftercare. Implications are drawn for staffing and structuring community mental health aftercare services in ways that are likely to enhance practitioner committment to aftercare.", "contents": "Commitment to community mental health aftercare services: staffing and structural implications. This study examines the views of community mental health practitioners toward aftercare services and deinstitutionalized patients. A survey of 361 practitioners in Allegheny County, Pennsylvania, finds that these views are related to practitioner experience in psychotherapeutic practice, professional affiliation, educational level, and amount of specialization in aftercare. Implications are drawn for staffing and structuring community mental health aftercare services in ways that are likely to enhance practitioner committment to aftercare."}
{"id": "PMID:213234", "title": "Reduction of adrenocorticotropic hormone (ACTH) and cortisol in drug addicts treated by acupuncture and electrical stimulation (AES).", "content": "Forty-two heroin addicts and 31 normal persons were examined for the effect of acupuncture and electrical stimulation (AES) on plasma ACTH, cortisol and cyclic-AMP levels. Both ACTH and cortisol levels were reduced significantly in the addicts after treatment whereas no such significant reduction was observed in the normals. Plasma cyclic-AMP level was not affected in either group. Taken together, results from the present study suggest that the mechanism of AES in the treatment of addiction may have a neuroendocrinological basis. This hypothesis is particularly attractive in view of the isolation of opiate-like peptides from the brain.", "contents": "Reduction of adrenocorticotropic hormone (ACTH) and cortisol in drug addicts treated by acupuncture and electrical stimulation (AES). Forty-two heroin addicts and 31 normal persons were examined for the effect of acupuncture and electrical stimulation (AES) on plasma ACTH, cortisol and cyclic-AMP levels. Both ACTH and cortisol levels were reduced significantly in the addicts after treatment whereas no such significant reduction was observed in the normals. Plasma cyclic-AMP level was not affected in either group. Taken together, results from the present study suggest that the mechanism of AES in the treatment of addiction may have a neuroendocrinological basis. This hypothesis is particularly attractive in view of the isolation of opiate-like peptides from the brain."}
{"id": "PMID:213235", "title": "Endocrinological aspects of PTH metabolism in the kidney.", "content": "Various methods for the measurement of intact PTH, PTH fragments and PTH binding to receptors were applied to clarify the role of renal receptors for the bioexpression of PTH. Glomerular receptors may contribute approximately 20% of the renal PTH catabolism. PTH also binds to tubular receptors at the luminal side (brush border membranes) as well as at the antiluminal site (basal-lateral membrane). Scatchard plot analysis of PTH binding to these receptors allows the calculation of an equilibrium dissociation constant and binding capacity, if correction is made for inactivation of bioactive PTH (measured by LAMA). Binding to receptors is--in our systems--invariably associated with degradation of the intact hormone to N-terminal and C-terminal fragments of different molecular weight. Antibodies against basal lateral membranes and against brush border membranes are able to inhibit PTH binding to tubular membranes. Sera of uremic patients with inappropriately high PTH contain a globulin which interferes with PTH binding to the receptor, suggesting that uremia may be another example for a \"hormone receptor antibody disease\".", "contents": "Endocrinological aspects of PTH metabolism in the kidney. Various methods for the measurement of intact PTH, PTH fragments and PTH binding to receptors were applied to clarify the role of renal receptors for the bioexpression of PTH. Glomerular receptors may contribute approximately 20% of the renal PTH catabolism. PTH also binds to tubular receptors at the luminal side (brush border membranes) as well as at the antiluminal site (basal-lateral membrane). Scatchard plot analysis of PTH binding to these receptors allows the calculation of an equilibrium dissociation constant and binding capacity, if correction is made for inactivation of bioactive PTH (measured by LAMA). Binding to receptors is--in our systems--invariably associated with degradation of the intact hormone to N-terminal and C-terminal fragments of different molecular weight. Antibodies against basal lateral membranes and against brush border membranes are able to inhibit PTH binding to tubular membranes. Sera of uremic patients with inappropriately high PTH contain a globulin which interferes with PTH binding to the receptor, suggesting that uremia may be another example for a \"hormone receptor antibody disease\"."}
{"id": "PMID:213236", "title": "A concept for the control of kidney production of erythropoietin involving prostaglandins and cyclic nucleotides.", "content": "Our hypothesis is that PGs released within the kidney play a role in the modulation of kidney production of Ep. PGs release probably at medullary and/or cortical sites following erythropoietic stimuli such as hypoxic hypoxia, anemic hypoxia, and ischemic hypoxia induced by renal artery constriction increase kidney production of Ep. PGs which are released probably activate a renal cortical adenylate cyclase thereby enhancing the production of intracellular cAMP. This initiates the cascade of events resulting in the production and/or secretion of Ep by the kidney. The endoperoxide analogs and PGE2 have been found to produce a dose-related and Ep-dependent increase in radioiron incorporation into newly formed red blood cells of exhypoxic polycythemic mice. Indomethacin, a potent PG cyclo-oxygenase inhibitior, attenuates Ep production and the appearance of PGE in the renal venous effluent of animals exposed to hypoxic hypoxia and renal artery constriction. Arachidonic acid (C20:4) and PGE2 infusion into the posthypoxic isolated perfused dog kidney produced a significant elevation in Ep titers in the perfusate. The increase in Ep production caused by arachidonate is blocked by indomethacin. It has been previously reported that PGs of the E series stimulate cAMP formation in several tissues. We have found that not only are renal cortical cAMP levels significantly elevated in rats following exposure to hypobaric hypoxia but that dibutyryl cAMP administration produces an increase in hematocrit and circulating red cell mass in normal mice. Our data thus far strongly support the hypothesis that the renal PGs and the cyclic nucleotides are intimately involved in the pharmacologic and/or pathophysiologic control of Ep production. Further work is necessary to determine whether the PGs and cyclic nucleotides are involved in the day-to-day control of Ep production by the mammalian kidney.", "contents": "A concept for the control of kidney production of erythropoietin involving prostaglandins and cyclic nucleotides. Our hypothesis is that PGs released within the kidney play a role in the modulation of kidney production of Ep. PGs release probably at medullary and/or cortical sites following erythropoietic stimuli such as hypoxic hypoxia, anemic hypoxia, and ischemic hypoxia induced by renal artery constriction increase kidney production of Ep. PGs which are released probably activate a renal cortical adenylate cyclase thereby enhancing the production of intracellular cAMP. This initiates the cascade of events resulting in the production and/or secretion of Ep by the kidney. The endoperoxide analogs and PGE2 have been found to produce a dose-related and Ep-dependent increase in radioiron incorporation into newly formed red blood cells of exhypoxic polycythemic mice. Indomethacin, a potent PG cyclo-oxygenase inhibitior, attenuates Ep production and the appearance of PGE in the renal venous effluent of animals exposed to hypoxic hypoxia and renal artery constriction. Arachidonic acid (C20:4) and PGE2 infusion into the posthypoxic isolated perfused dog kidney produced a significant elevation in Ep titers in the perfusate. The increase in Ep production caused by arachidonate is blocked by indomethacin. It has been previously reported that PGs of the E series stimulate cAMP formation in several tissues. We have found that not only are renal cortical cAMP levels significantly elevated in rats following exposure to hypobaric hypoxia but that dibutyryl cAMP administration produces an increase in hematocrit and circulating red cell mass in normal mice. Our data thus far strongly support the hypothesis that the renal PGs and the cyclic nucleotides are intimately involved in the pharmacologic and/or pathophysiologic control of Ep production. Further work is necessary to determine whether the PGs and cyclic nucleotides are involved in the day-to-day control of Ep production by the mammalian kidney."}
{"id": "PMID:213237", "title": "Diseases transmitted from pets to man: an evolving concern for veterinarians.", "content": "Pets are not a major source of human infections but they can transmit certain diseases to man. This transmission usually is complex, requiring close contact with pets or their excretions and frequently involves a breach of sound hygienic practice. In some instances, pathogens of animal origin are acquired inadvertently because  infectivity can persist after evidence of gross contamination has gone. Veterinarians participate in controlling zoonotic diseases by encouraging rabies vaccination and hygienic treatment of pet feces and urine, by supporting community efforts toward responsible pet ownership and by advising on precautions for handling sick animals. It is recommended that veterinarians discourage the keeping of wild or exotic animals as pets and excess fondling of pets (particularly by children and pregnant women). Clients and kennel workers should be advised to use caution with animals that have aborted.", "contents": "Diseases transmitted from pets to man: an evolving concern for veterinarians. Pets are not a major source of human infections but they can transmit certain diseases to man. This transmission usually is complex, requiring close contact with pets or their excretions and frequently involves a breach of sound hygienic practice. In some instances, pathogens of animal origin are acquired inadvertently because  infectivity can persist after evidence of gross contamination has gone. Veterinarians participate in controlling zoonotic diseases by encouraging rabies vaccination and hygienic treatment of pet feces and urine, by supporting community efforts toward responsible pet ownership and by advising on precautions for handling sick animals. It is recommended that veterinarians discourage the keeping of wild or exotic animals as pets and excess fondling of pets (particularly by children and pregnant women). Clients and kennel workers should be advised to use caution with animals that have aborted."}
{"id": "PMID:213238", "title": "Cerebral granular cell tumor (myoblastoma) in a dog: case report and literature review.", "content": "An infiltrative granular cell tumor (myoblastoma) occurred in the superficial parieto-occipital cortex of an ataxic 12-year-old dog. The neoplasm was characterized by cells with numerous small PAS-positive, diastase-resistant cytoplasmic granules. The neoplasm also had numerous cells with large globular PAS-positive bodies (angulate bodies). Ultrastructurally, the neoplastic cells were characterized by numerous homogenous electron-dense, sharply bounded granules and large pleomorphic, indistinctly bounded granules. The angulate bodies were composed of 8- to 10-nm fibrils, a few of which formed parallel arrays or tubule-like structures. This represents the first report of a granular cell tumor in the central nervous system of the dog.", "contents": "Cerebral granular cell tumor (myoblastoma) in a dog: case report and literature review. An infiltrative granular cell tumor (myoblastoma) occurred in the superficial parieto-occipital cortex of an ataxic 12-year-old dog. The neoplasm was characterized by cells with numerous small PAS-positive, diastase-resistant cytoplasmic granules. The neoplasm also had numerous cells with large globular PAS-positive bodies (angulate bodies). Ultrastructurally, the neoplastic cells were characterized by numerous homogenous electron-dense, sharply bounded granules and large pleomorphic, indistinctly bounded granules. The angulate bodies were composed of 8- to 10-nm fibrils, a few of which formed parallel arrays or tubule-like structures. This represents the first report of a granular cell tumor in the central nervous system of the dog."}
{"id": "PMID:213253", "title": "Species differences in the hepatic response to mirex: ultrastructural and histochemical studies.", "content": "Mirex was fed at levels of 1, 5, 15, and 30 ppm to mice, 5 and 30 ppm to rats, while monkeys received the chemical by stomach tube at levels of 0.25 and 1 mg/kg (equal to 5 and 20 ppm). Mice were killed and their livers obtained at 2, 4, 6, 9, 10, 15 and 18 months, whereas rats were killed and surgical biopsies were taken at 16, 19, 26, and 36 months. Cytochemical techniques were employed to detect activities of lysosomal beta-glycerol phosphatase (ACpase) and glucose 6-phosphatase (G-6-pase). ACpase and G-6-pase remained unchanged and comparable to controls in livers of mice receiving 1 ppm. G-6-pase decreased in centrilobular areas while ACpase increased with time in the higher groups. At 12 months, liver cells that lost their G-6-pase activity surrounded by Kupffer cells that contained strong ACpase. In contrast, rat livers had no increase in ACpase and little loss in G-6-pase. Surprisingly, and in spite of the high levels of mirex ingested, monkey livers showed no loss of G-6-pase or activation of ACpase. Ultrastructurally, the underlying feature in all livers was proliferation of smooth endoplasmic reticulum (SER) displaying species variation. Thus, in mice, intense proliferation of SER that was both time- and dose-dependent was localized in specific regions of the cytosol. Hepatic cells, damaged and necrotic in mice fed 5, 15, and 30 ppm, were phagocytosed by activated Kupffer cells. SER proliferation in rat and monkey liver cells was less conspicuous than in mice. Except for this change, rat and monkey liver cells were normal. There studies emphasize species and enzyme variations in response to mirex. An interesting aspect observed was the lack of lysosomal catabolism during liver enlargement.", "contents": "Species differences in the hepatic response to mirex: ultrastructural and histochemical studies. Mirex was fed at levels of 1, 5, 15, and 30 ppm to mice, 5 and 30 ppm to rats, while monkeys received the chemical by stomach tube at levels of 0.25 and 1 mg/kg (equal to 5 and 20 ppm). Mice were killed and their livers obtained at 2, 4, 6, 9, 10, 15 and 18 months, whereas rats were killed and surgical biopsies were taken at 16, 19, 26, and 36 months. Cytochemical techniques were employed to detect activities of lysosomal beta-glycerol phosphatase (ACpase) and glucose 6-phosphatase (G-6-pase). ACpase and G-6-pase remained unchanged and comparable to controls in livers of mice receiving 1 ppm. G-6-pase decreased in centrilobular areas while ACpase increased with time in the higher groups. At 12 months, liver cells that lost their G-6-pase activity surrounded by Kupffer cells that contained strong ACpase. In contrast, rat livers had no increase in ACpase and little loss in G-6-pase. Surprisingly, and in spite of the high levels of mirex ingested, monkey livers showed no loss of G-6-pase or activation of ACpase. Ultrastructurally, the underlying feature in all livers was proliferation of smooth endoplasmic reticulum (SER) displaying species variation. Thus, in mice, intense proliferation of SER that was both time- and dose-dependent was localized in specific regions of the cytosol. Hepatic cells, damaged and necrotic in mice fed 5, 15, and 30 ppm, were phagocytosed by activated Kupffer cells. SER proliferation in rat and monkey liver cells was less conspicuous than in mice. Except for this change, rat and monkey liver cells were normal. There studies emphasize species and enzyme variations in response to mirex. An interesting aspect observed was the lack of lysosomal catabolism during liver enlargement."}
{"id": "PMID:213255", "title": "[Evolution over time of the electroencephalographic signal. Application in pharmacology].", "content": "The dynamics of transition from wakefulness to drowsiness can be modified by psycho-active compounds. These two states of vigilance have different electroencephalographic characteristics, which can be also modified by the administration of substances. This paper describes a method intended to discriminate between these two aspects of drug action, using a mini-computer. Investigation of sleep-wakefulness cycles with continuous EEG and EMG recording necessitates an efficient method of data reduction. On-line computation of Hjorth parameters with a micro-computer, and further processing witha mini-computer has been used. A pharmacological approach to the study of sleep-wakefulness cycles is proposed; this avoids a strict distinction of sleep phases, and concentrates on the coninuum of vigilance states. Differents ways of showing drug-induced modifications on that continuum are presented with examples.", "contents": "[Evolution over time of the electroencephalographic signal. Application in pharmacology]. The dynamics of transition from wakefulness to drowsiness can be modified by psycho-active compounds. These two states of vigilance have different electroencephalographic characteristics, which can be also modified by the administration of substances. This paper describes a method intended to discriminate between these two aspects of drug action, using a mini-computer. Investigation of sleep-wakefulness cycles with continuous EEG and EMG recording necessitates an efficient method of data reduction. On-line computation of Hjorth parameters with a micro-computer, and further processing witha mini-computer has been used. A pharmacological approach to the study of sleep-wakefulness cycles is proposed; this avoids a strict distinction of sleep phases, and concentrates on the coninuum of vigilance states. Differents ways of showing drug-induced modifications on that continuum are presented with examples."}
{"id": "PMID:213256", "title": "Gonadotropin induced stimulation and desensitization of cyclic 3', 5' -adenosine monophosphate dependent protein kinase(s) in the rat ovary.", "content": "Incubation of rat ovarian slices with choriogonadotropin resulted in stimulation of cyclic AMP dependent protein kinase activity in a time and dose dependent manner. However, prior exposure of animals to choriogonadotropin in vivo resulted in a decreased sensitivity to subsequent in vitro stimulation by the same hormone. This decreased sensitivity was due to a lesion in the hormone receptor adenylate cyclase system rather than a change in the property of protein kinase with respect to its stimulation by cyclic AMP. Unchanged levels of cyclic AMP formation in these ovaries were evidenced by the lack of inhibition of [3H] cyclic AMP binding. In the untreated controls, however, choriogonadotropin in vitro resulted in inhibition [3H] cyclic AMP binding activity suggesting endogenous occupation parallel to protein kinase activation. These results are indicative of the linear coupling of hormone receptor-adenylate cyclase-protein kinase system and point out the in vivo role of protein kinase activation in choriogonadotropin mediated regulation of ovarian function.", "contents": "Gonadotropin induced stimulation and desensitization of cyclic 3', 5' -adenosine monophosphate dependent protein kinase(s) in the rat ovary. Incubation of rat ovarian slices with choriogonadotropin resulted in stimulation of cyclic AMP dependent protein kinase activity in a time and dose dependent manner. However, prior exposure of animals to choriogonadotropin in vivo resulted in a decreased sensitivity to subsequent in vitro stimulation by the same hormone. This decreased sensitivity was due to a lesion in the hormone receptor adenylate cyclase system rather than a change in the property of protein kinase with respect to its stimulation by cyclic AMP. Unchanged levels of cyclic AMP formation in these ovaries were evidenced by the lack of inhibition of [3H] cyclic AMP binding. In the untreated controls, however, choriogonadotropin in vitro resulted in inhibition [3H] cyclic AMP binding activity suggesting endogenous occupation parallel to protein kinase activation. These results are indicative of the linear coupling of hormone receptor-adenylate cyclase-protein kinase system and point out the in vivo role of protein kinase activation in choriogonadotropin mediated regulation of ovarian function."}
{"id": "PMID:213257", "title": "Corticosteroid response of rabbits and rats to exogenous ACTH.", "content": "The dynamics of the alterations of the cortisol: corticosterone ratio in rabbits during porcine ACTH administration were studied on an almost daily basis and as a function of time after injection. In rabbits the cortisol: corticosterone ratio increased strikingly but variably during the treatment period. Rats responded to similar treatment only with increased corticosterone release. The differences are attributed to the presence of 1-39 ACTH as well as intermediate ACTH in the rabbit pituitary but not in the rat pituitary.", "contents": "Corticosteroid response of rabbits and rats to exogenous ACTH. The dynamics of the alterations of the cortisol: corticosterone ratio in rabbits during porcine ACTH administration were studied on an almost daily basis and as a function of time after injection. In rabbits the cortisol: corticosterone ratio increased strikingly but variably during the treatment period. Rats responded to similar treatment only with increased corticosterone release. The differences are attributed to the presence of 1-39 ACTH as well as intermediate ACTH in the rabbit pituitary but not in the rat pituitary."}
{"id": "PMID:213258", "title": "Characterization of specific prostaglandin E receptor in isolated rat Leydig cells.", "content": "The binding of 3H-prostaglandin E1 (PGE1) to the isolated Leydig cells from rat testes was studied under different experimental conditions. The Scatchard plot analysis showed two populations of specific binding sites: one of a high affinity and low capacity (Ka1 = 2.2 x 10(8) mol-1 l) and the other with less affinity and high capacity (Ka2 = 8.7 x 10(7) mol-1 l). Maximum specific binding occurred at pH 7.4 and 22 degrees C. Unlabelled PGE1 and PGE2 inhibited the binding in a dose-dependent manner, while about 10 times higher amount of PGA1 was necessary to show a similar effect. Moreover, the treatment of Leydig cells with disulfide modifying agents (dithiotreitol and mercaptoethanol) decreased 3H-PGE1 binding. Finally, the production of cAMP was 4.5 times increased (P less than 0.001) after 20 min incubation of Leydig cells with PGE1 and aminophylline, while that of testosterone was 2.5 times increased (P less than 0.001) after 3 h incubation with PGE1.", "contents": "Characterization of specific prostaglandin E receptor in isolated rat Leydig cells. The binding of 3H-prostaglandin E1 (PGE1) to the isolated Leydig cells from rat testes was studied under different experimental conditions. The Scatchard plot analysis showed two populations of specific binding sites: one of a high affinity and low capacity (Ka1 = 2.2 x 10(8) mol-1 l) and the other with less affinity and high capacity (Ka2 = 8.7 x 10(7) mol-1 l). Maximum specific binding occurred at pH 7.4 and 22 degrees C. Unlabelled PGE1 and PGE2 inhibited the binding in a dose-dependent manner, while about 10 times higher amount of PGA1 was necessary to show a similar effect. Moreover, the treatment of Leydig cells with disulfide modifying agents (dithiotreitol and mercaptoethanol) decreased 3H-PGE1 binding. Finally, the production of cAMP was 4.5 times increased (P less than 0.001) after 20 min incubation of Leydig cells with PGE1 and aminophylline, while that of testosterone was 2.5 times increased (P less than 0.001) after 3 h incubation with PGE1."}
{"id": "PMID:213259", "title": "Activity of adenylate cyclase and phospodiesterase in the pituitary and thyroid during postnatal period in rats.", "content": "Adenylate cyclase (AC) and phosphodiesterase (PD) activities in the pituitary and thyroid have been determined during postnatal period in rats. In both tissues the activity of both enzymes was found early after birth. In the pituitary gland AC activity increased significantly from the second to the seventh day, while it remained unchanged on the 16 th day and again increased on the 23rd day when the activity reached the value of adult rats. The activity of PD in the pituitary increased significantly from the second to 23rd postnatal day and in the adult rats the activity was similar as in two days old rats. In the thyroid gland AC activity remained unchanged during postnatal period of rats with the exception between the 16th and 23rd day when a small but significant difference was found. The activity of PD in thyroid was high on the first day after delivery and then decreased significantly on the seventh day. It increased again significantly on 23rd day when it was similar to the adult rats. However, between 23rd and 60th days the activity significantly dropped and significantly increased from 60th day to the adult age. These results suggest that in the rat the mechanism of adenylate cyclase system involved in the pituitary and thyroid functions could play a role in the regulation of the function of these tissues during postnatal development.", "contents": "Activity of adenylate cyclase and phospodiesterase in the pituitary and thyroid during postnatal period in rats. Adenylate cyclase (AC) and phosphodiesterase (PD) activities in the pituitary and thyroid have been determined during postnatal period in rats. In both tissues the activity of both enzymes was found early after birth. In the pituitary gland AC activity increased significantly from the second to the seventh day, while it remained unchanged on the 16 th day and again increased on the 23rd day when the activity reached the value of adult rats. The activity of PD in the pituitary increased significantly from the second to 23rd postnatal day and in the adult rats the activity was similar as in two days old rats. In the thyroid gland AC activity remained unchanged during postnatal period of rats with the exception between the 16th and 23rd day when a small but significant difference was found. The activity of PD in thyroid was high on the first day after delivery and then decreased significantly on the seventh day. It increased again significantly on 23rd day when it was similar to the adult rats. However, between 23rd and 60th days the activity significantly dropped and significantly increased from 60th day to the adult age. These results suggest that in the rat the mechanism of adenylate cyclase system involved in the pituitary and thyroid functions could play a role in the regulation of the function of these tissues during postnatal development."}
{"id": "PMID:213260", "title": "Studies on adrenaline-induced lipolysis in adrenalectomized rats.", "content": "In a short-term study, adrenaline-induced lipolysis was less in adrenalectomized rats than in controls, though the cyclic AMP accumulation was not different. In adrenalectomized rats treated with corticosterone, lipase activity was as low as in untreated adrenalectomized rats, although adrenaline-induced lipolysis was not reduced. In a long-term study, no reduction in adrenaline-induced lipolysis or cyclic AMP accumulation was observed in adrenalectomized rats. The mechanism of the effect of adrenalectomy on adrenaline-induced lipolysis is discussed on the basis of these results.", "contents": "Studies on adrenaline-induced lipolysis in adrenalectomized rats. In a short-term study, adrenaline-induced lipolysis was less in adrenalectomized rats than in controls, though the cyclic AMP accumulation was not different. In adrenalectomized rats treated with corticosterone, lipase activity was as low as in untreated adrenalectomized rats, although adrenaline-induced lipolysis was not reduced. In a long-term study, no reduction in adrenaline-induced lipolysis or cyclic AMP accumulation was observed in adrenalectomized rats. The mechanism of the effect of adrenalectomy on adrenaline-induced lipolysis is discussed on the basis of these results."}
{"id": "PMID:213261", "title": "Changes in the cyclic nucleotides of rat thyroid, pituitary and plasma caused by methylthiouracil treatment.", "content": "Changes in the content of cyclic nucleotides (cAMP and cGMP) and related enzyme activities were observed in the rat thyroid, pituitary and plasma during the prolonged increase of endogenous TSH produced by treatment with methylthiouracil (MTU). Experiments were performed after 4 weeks treatment with MTU. The wet weight and cAMP content per wet weight of the thyroid increased 3 and 1.4 times respectively, but cGMP showed a slight decrease. Pituitary weight increased 1.3 times, but cAMP and cGMP content did not change. The cAMP level in plasma also increased about 1.3 times, but cGMP did not increase. The cAMP-phosphodiesterase activity in the thyroid, pituitary and plasma was increased 1.9, 1.4 and 1.3 times respectively after MTU treatment, while cGMP-phosphodiesterase showed no significant change. ATPase activity in the thyroid and pituitary was also increased more than 1.5 times after MTU treatment, while 5'-nucleotidase activitity decreased remarkably. These data indicate that the metabolism of the cyclic nucleotide system in the thyroid is stimulated by TSH.", "contents": "Changes in the cyclic nucleotides of rat thyroid, pituitary and plasma caused by methylthiouracil treatment. Changes in the content of cyclic nucleotides (cAMP and cGMP) and related enzyme activities were observed in the rat thyroid, pituitary and plasma during the prolonged increase of endogenous TSH produced by treatment with methylthiouracil (MTU). Experiments were performed after 4 weeks treatment with MTU. The wet weight and cAMP content per wet weight of the thyroid increased 3 and 1.4 times respectively, but cGMP showed a slight decrease. Pituitary weight increased 1.3 times, but cAMP and cGMP content did not change. The cAMP level in plasma also increased about 1.3 times, but cGMP did not increase. The cAMP-phosphodiesterase activity in the thyroid, pituitary and plasma was increased 1.9, 1.4 and 1.3 times respectively after MTU treatment, while cGMP-phosphodiesterase showed no significant change. ATPase activity in the thyroid and pituitary was also increased more than 1.5 times after MTU treatment, while 5'-nucleotidase activitity decreased remarkably. These data indicate that the metabolism of the cyclic nucleotide system in the thyroid is stimulated by TSH."}
{"id": "PMID:213263", "title": "Enzymatic oxidation of mercaptoethanol to isethinic acid and isethionic acid.", "content": "The enzymatic oxidation of mercaptoethanol by purified cysteamine oxygenase has been studied. Products were identified by chromatography as isethinic acid (2-hydroxyethan-sulfinic acid) and isethionic acid. Other features of the reaction, as cofactor requirement, the influence of the enzyme concentration on the stage of oxidation, the biological significance of this reaction are also discussed.", "contents": "Enzymatic oxidation of mercaptoethanol to isethinic acid and isethionic acid. The enzymatic oxidation of mercaptoethanol by purified cysteamine oxygenase has been studied. Products were identified by chromatography as isethinic acid (2-hydroxyethan-sulfinic acid) and isethionic acid. Other features of the reaction, as cofactor requirement, the influence of the enzyme concentration on the stage of oxidation, the biological significance of this reaction are also discussed."}
{"id": "PMID:213265", "title": "beta-Glucuronidase activity in trained red and white skeletal muscle of mice.", "content": "We studied the effects of prolonged running exercise (5 days a week, 1.5 h per day at a speed of 17.6 m/min) on the activity of some acid hydrolases (beta-glucuronidase, beta-N-acetylglucosaminidase, acid phosphatase and cathepsin D) and three enzymes of energy metabolism (cytochrome c oxidase, lactate dehydrogenase and creatine kinase) in the distal and in the proximal, the predominantly white and red parts, respectively, of the vastus lateralis-muscle from mice. The acid hydrolase activity levels were 1.24--1.69 higher in untrained red muscle compared to untrained white muscle. The light training applied increased the activity of beta-glucuronidase in both red and white muscle. No other significant training effects were observed in the enzyme activities measured.", "contents": "beta-Glucuronidase activity in trained red and white skeletal muscle of mice. We studied the effects of prolonged running exercise (5 days a week, 1.5 h per day at a speed of 17.6 m/min) on the activity of some acid hydrolases (beta-glucuronidase, beta-N-acetylglucosaminidase, acid phosphatase and cathepsin D) and three enzymes of energy metabolism (cytochrome c oxidase, lactate dehydrogenase and creatine kinase) in the distal and in the proximal, the predominantly white and red parts, respectively, of the vastus lateralis-muscle from mice. The acid hydrolase activity levels were 1.24--1.69 higher in untrained red muscle compared to untrained white muscle. The light training applied increased the activity of beta-glucuronidase in both red and white muscle. No other significant training effects were observed in the enzyme activities measured."}
{"id": "PMID:213267", "title": "Immunological studies on cytochrome c oxidase: arrangements of protein subunits in the solubilized and membrane-bound enzyme.", "content": "Seven protein subunits of cytochrome c oxidase from bovine heart were isolated by gel filtration in the presence of sodium dodecyl sulphate (subunits I, II and III) and guanidine hydrochloride (subunits V, VI and VII), and ion-exchange chromatography in 6 M urea (subunit IV) after the enzyme had been dissociated in 6 M guanidine hydrochloride. When analysed by highly cross-linked sodium dodecyl sulphate/polyacrylamide gel electrophoresis in the presence of urea, the apparent molecular weights were = I, 36700; II, 24300; III, 20400; IV, 17300; V, 12300; VI, 8700: and VII, 5100. Monospecific rabbit antisera were obtained against subunits I, IV, V, VI and VII and a mixture of subunits II and III. These subunit-specific antisera with the exception of anti-I serum all cross-reacted with the detergent-solubilized native oxidase. Enzymatic studies on purified oxidase indicated that immunoglobulins against subunits II + III, IV, V, VI and VII respectively caused 25, 65, 20, 30 and 25% inhibition while anti-I immunoglobulin did not inhibit the activity. The subunit-specific antisera were used to examine the arrangements of the subunits in the membrane. Enzymatic studies using bovine heart mitochondria and rat liver mitochondrial digitonin particles showed that anti-(II + III) serum, anti-V serum and anti-VII serum all inhibited the oxidase activity while the other antisera did not. On the other hand, results of using 125I-labelled immunoglobulins showed that anti-IV, anti-V and anti-VII sera were bound to the surface of inverted vesicles (matrix side) while all other antisera were not. These results indicate that cytochrome oxidase subunits II and III are situated on the outer surface, and subunit IV is exclusively on the matrix surface while subunits V and VII are exposed on both surfaces of the mitochondrial membrane. Subunits I and VI are buried within the membrane, not exposed on either side.", "contents": "Immunological studies on cytochrome c oxidase: arrangements of protein subunits in the solubilized and membrane-bound enzyme. Seven protein subunits of cytochrome c oxidase from bovine heart were isolated by gel filtration in the presence of sodium dodecyl sulphate (subunits I, II and III) and guanidine hydrochloride (subunits V, VI and VII), and ion-exchange chromatography in 6 M urea (subunit IV) after the enzyme had been dissociated in 6 M guanidine hydrochloride. When analysed by highly cross-linked sodium dodecyl sulphate/polyacrylamide gel electrophoresis in the presence of urea, the apparent molecular weights were = I, 36700; II, 24300; III, 20400; IV, 17300; V, 12300; VI, 8700: and VII, 5100. Monospecific rabbit antisera were obtained against subunits I, IV, V, VI and VII and a mixture of subunits II and III. These subunit-specific antisera with the exception of anti-I serum all cross-reacted with the detergent-solubilized native oxidase. Enzymatic studies on purified oxidase indicated that immunoglobulins against subunits II + III, IV, V, VI and VII respectively caused 25, 65, 20, 30 and 25% inhibition while anti-I immunoglobulin did not inhibit the activity. The subunit-specific antisera were used to examine the arrangements of the subunits in the membrane. Enzymatic studies using bovine heart mitochondria and rat liver mitochondrial digitonin particles showed that anti-(II + III) serum, anti-V serum and anti-VII serum all inhibited the oxidase activity while the other antisera did not. On the other hand, results of using 125I-labelled immunoglobulins showed that anti-IV, anti-V and anti-VII sera were bound to the surface of inverted vesicles (matrix side) while all other antisera were not. These results indicate that cytochrome oxidase subunits II and III are situated on the outer surface, and subunit IV is exclusively on the matrix surface while subunits V and VII are exposed on both surfaces of the mitochondrial membrane. Subunits I and VI are buried within the membrane, not exposed on either side."}
{"id": "PMID:213268", "title": "Partial purification and characterization of rat-liver messenger RNA coding for phosphoenolpyruvate carboxykinase (GTP).", "content": "The mRNA coding for the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) was partially purified from the liver of cyclic-AMP-treated rats by a procedure involving multiple oligo(dT)-cellulose chromatographies and sucrose gradient fractionations. The purification was monitored by translational assay using a wheat germ extract. Relative to RNA bound once to oligo(dT)-cellulose, the final material was enriched 20-fold in template activity for phosphoenolpyruvate carboxykinase synthesis. With this RNA preparation, cell-free enzyme synthesis amounted to 5% of total mRNA-directed protein synthesis. The apparent sedimentation coefficient of phosphoenolpyruvate carboxykinase mRNA in sucrose gradients was between 20 and 22 S, corresponding to an average molecular weight of 0.93 X 10(6). By formamide/polyacrylamide gel electrophoresis the molecular weight of the enzyme mRNA was estimated at between 0.91 X 10(6) and 1.12 X 10(6). From these estimates, it was concluded that considerable non-coding sequence(s) are present in the mRNA. Approximately 20% of the enzyme mRNA in rat liver failed to bind to oligo(dT)-cellulose, presumably because of the absence of a poly(A) segment. The translation of phosphoenolpyruvate carboxykinase mRNA by the wheat germ extract was inhibited in the presence of 7-methylguanosine 5'-phosphate. The enzyme mRNA appears therefore to have a 'cap' at the 5' end.", "contents": "Partial purification and characterization of rat-liver messenger RNA coding for phosphoenolpyruvate carboxykinase (GTP). The mRNA coding for the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) was partially purified from the liver of cyclic-AMP-treated rats by a procedure involving multiple oligo(dT)-cellulose chromatographies and sucrose gradient fractionations. The purification was monitored by translational assay using a wheat germ extract. Relative to RNA bound once to oligo(dT)-cellulose, the final material was enriched 20-fold in template activity for phosphoenolpyruvate carboxykinase synthesis. With this RNA preparation, cell-free enzyme synthesis amounted to 5% of total mRNA-directed protein synthesis. The apparent sedimentation coefficient of phosphoenolpyruvate carboxykinase mRNA in sucrose gradients was between 20 and 22 S, corresponding to an average molecular weight of 0.93 X 10(6). By formamide/polyacrylamide gel electrophoresis the molecular weight of the enzyme mRNA was estimated at between 0.91 X 10(6) and 1.12 X 10(6). From these estimates, it was concluded that considerable non-coding sequence(s) are present in the mRNA. Approximately 20% of the enzyme mRNA in rat liver failed to bind to oligo(dT)-cellulose, presumably because of the absence of a poly(A) segment. The translation of phosphoenolpyruvate carboxykinase mRNA by the wheat germ extract was inhibited in the presence of 7-methylguanosine 5'-phosphate. The enzyme mRNA appears therefore to have a 'cap' at the 5' end."}
{"id": "PMID:213269", "title": "Modulation of adenylate cyclase/cyclic AMP response by thyrotropin and prostaglandin E2 in cultured thyroid cells. 1. Negative regulation.", "content": "Isolated porcine thyroid cells, cultured in the presence of thyrotropin (greater than or equal to 0.25 mU/ml) or prostaglandin E2 (greater than or equal to 0.1 micron), showed decreased adenosine 3':5'-monophosphate (cyclic AMP) response to further thyrotropin or prostaglandin E2 stimulation, respectively. Kinetics of the refractory process to thyrotropin and prostaglandin E2 are different: (a) maximal refractoriness to prostaglandin E2 was attained after 2--6 h exposure to prostaglandin E2 while refractoriness to thyrotropin was maximal only after 12--24 h; (b) the degree of refractoriness to prostaglandin E2 was much greater than that to thyrotropin. Refractoriness to thyrotropin or prostaglandin E2 is characterized: by specificity for each thyroid stimulator; by dependence upon the dose of thyrotropin or prostaglandin E2 in culture, e.g. induction of high degree of refractoriness with 0.5 mU/ml thyrotropin (or 1 micron prostaglandin E2), which elicits only a small cyclic AMP increase; by time requirement for induction; by partial effect; by changes of maximum activation of cyclic AMP response; by reversibility. This refractoriness of the cyclic AMP response was not induced by dibutyryl adenosine 3':5'-monophosphate. It was not attributed to increased cyclic AMP-phosphodiesterase activity, but to alterations in the receptor-adenylate cyclase system. Prevention of refractoriness to thyrotropin or prostaglandin E2 by incubation of cells in the presence of actinomycin D, puromycin and cycloheximide suggests that new RNA and protein syntheses are required for the development of the refractory state.", "contents": "Modulation of adenylate cyclase/cyclic AMP response by thyrotropin and prostaglandin E2 in cultured thyroid cells. 1. Negative regulation. Isolated porcine thyroid cells, cultured in the presence of thyrotropin (greater than or equal to 0.25 mU/ml) or prostaglandin E2 (greater than or equal to 0.1 micron), showed decreased adenosine 3':5'-monophosphate (cyclic AMP) response to further thyrotropin or prostaglandin E2 stimulation, respectively. Kinetics of the refractory process to thyrotropin and prostaglandin E2 are different: (a) maximal refractoriness to prostaglandin E2 was attained after 2--6 h exposure to prostaglandin E2 while refractoriness to thyrotropin was maximal only after 12--24 h; (b) the degree of refractoriness to prostaglandin E2 was much greater than that to thyrotropin. Refractoriness to thyrotropin or prostaglandin E2 is characterized: by specificity for each thyroid stimulator; by dependence upon the dose of thyrotropin or prostaglandin E2 in culture, e.g. induction of high degree of refractoriness with 0.5 mU/ml thyrotropin (or 1 micron prostaglandin E2), which elicits only a small cyclic AMP increase; by time requirement for induction; by partial effect; by changes of maximum activation of cyclic AMP response; by reversibility. This refractoriness of the cyclic AMP response was not induced by dibutyryl adenosine 3':5'-monophosphate. It was not attributed to increased cyclic AMP-phosphodiesterase activity, but to alterations in the receptor-adenylate cyclase system. Prevention of refractoriness to thyrotropin or prostaglandin E2 by incubation of cells in the presence of actinomycin D, puromycin and cycloheximide suggests that new RNA and protein syntheses are required for the development of the refractory state."}
{"id": "PMID:213270", "title": "Modulation of adenylate cyclase/cyclic AMP response by thyrotropin and prostaglandin E2 in cultured thyroid cells. 2. Positive regulation.", "content": "Two different independent processes are operating in cultured thyroid cells to regulate adenylate cyclase/cyclic AMP responsiveness to thyroid stimulators (thyrotropin and prostaglandin E2): firstly, refractoriness or negative regulation [preceding paper], which is specific for each thyroid stimulator, is not mediated by cyclic AMP and is not accompanied by alteration of adenylate cyclase activity; secondly, positive regulation which is characterized by an augmentation of the cyclic AMP response stimulated by thyrotropin and prostaglandin E2. This process is not specific for each thyroid stimulator and is a state of increased susceptibility of cyclic AMP synthesis to stimulation, accompanied by increased activity of the catalytic subunit of adenylate cyclase. Positive regulation is apparently mediated by increased intracellular cyclic AMP levels. It is a time-dependent and dose-dependent process. Very low concentrations (5-50 micronU/ml) of thyrotropin augmented cyclic AMP synthesis stimulated by thyrotropin and prostaglandin E2 whereas higher concentrations (above 0.1 mU/ml) augmented prostaglandin E2 stimulation but induced refractoriness to thyrotropin. Prostaglandin E2 (0.1 to 10 micronM) augmented thyrotropin stimulation and dibutyryl adenosine 3':5'-monophosphate (0.3 to 2 mM) augmented thyrotropin and prostaglandin E2 stimulation. Positive regulation is a slow process which develops within days and increases up to day 5 in culture. Experiments using inhibitors suggested that protein synthesis is required for the full expression of the increase in adenylate cyclase activity induced by the studied thyroid stimulators.", "contents": "Modulation of adenylate cyclase/cyclic AMP response by thyrotropin and prostaglandin E2 in cultured thyroid cells. 2. Positive regulation. Two different independent processes are operating in cultured thyroid cells to regulate adenylate cyclase/cyclic AMP responsiveness to thyroid stimulators (thyrotropin and prostaglandin E2): firstly, refractoriness or negative regulation [preceding paper], which is specific for each thyroid stimulator, is not mediated by cyclic AMP and is not accompanied by alteration of adenylate cyclase activity; secondly, positive regulation which is characterized by an augmentation of the cyclic AMP response stimulated by thyrotropin and prostaglandin E2. This process is not specific for each thyroid stimulator and is a state of increased susceptibility of cyclic AMP synthesis to stimulation, accompanied by increased activity of the catalytic subunit of adenylate cyclase. Positive regulation is apparently mediated by increased intracellular cyclic AMP levels. It is a time-dependent and dose-dependent process. Very low concentrations (5-50 micronU/ml) of thyrotropin augmented cyclic AMP synthesis stimulated by thyrotropin and prostaglandin E2 whereas higher concentrations (above 0.1 mU/ml) augmented prostaglandin E2 stimulation but induced refractoriness to thyrotropin. Prostaglandin E2 (0.1 to 10 micronM) augmented thyrotropin stimulation and dibutyryl adenosine 3':5'-monophosphate (0.3 to 2 mM) augmented thyrotropin and prostaglandin E2 stimulation. Positive regulation is a slow process which develops within days and increases up to day 5 in culture. Experiments using inhibitors suggested that protein synthesis is required for the full expression of the increase in adenylate cyclase activity induced by the studied thyroid stimulators."}
{"id": "PMID:213272", "title": "Carbon-13 nuclear-magnetic-resonance spectra of adenine cyclonucleosides and their phosphates. Effects of neighboring groups for elucidation of fine structure of nucleosides and nucleotides.", "content": "Carbon-13 nuclear magnetic resonance spectra of adenine cyclonucleosides, which have a fixed glycosidic conformation in an anti range, and their isopropylidene and phosphate esters are reported; those of 9-beta-D-arabinofuranosyladenine and its 5'-phosphate are also presented. The chemical shifts of the base carbons are affected not only by the bridging atom but also by the position of the bridged sugar carbon which determine the planarity of the third ring formed by cyclization between the base and the sugar. The effects of glycosidic conformation on the sugar-carbon chemical shifts are discussed by comparison of the data for 8:5'-cycloadenosines with the data for adenosine and its 8-substituted derivatives. The effects of a 2'-oxygen on sugar-carbon chemical shifts have been examined by comparing the data for 2'-deoxyadenosine, arabinosyladenine and 8:2'-anhydro-8-oxy-9-beta-D-arabinofuranosyladenine. The effects of phosphomonoester groups on base and sugar carbon resonances have been examined and it is noted that these groups cause downfield shifts for C-8 of all cyclonucleotides. Data for the 3':5'-cyclic monophosphate derivative of 8:2'-anhydro-8-thio-9-beta-D-arabinofuranosyladenine suggest that the previous assignments of C-4' and C-3' for nucleoside 3':5'-cyclic monophosphates must be reversed. According to the reversed assignments, it seems that C-3' and C-5' show moderate downfield shifts and C-4' shows a marked upfield shift.", "contents": "Carbon-13 nuclear-magnetic-resonance spectra of adenine cyclonucleosides and their phosphates. Effects of neighboring groups for elucidation of fine structure of nucleosides and nucleotides. Carbon-13 nuclear magnetic resonance spectra of adenine cyclonucleosides, which have a fixed glycosidic conformation in an anti range, and their isopropylidene and phosphate esters are reported; those of 9-beta-D-arabinofuranosyladenine and its 5'-phosphate are also presented. The chemical shifts of the base carbons are affected not only by the bridging atom but also by the position of the bridged sugar carbon which determine the planarity of the third ring formed by cyclization between the base and the sugar. The effects of glycosidic conformation on the sugar-carbon chemical shifts are discussed by comparison of the data for 8:5'-cycloadenosines with the data for adenosine and its 8-substituted derivatives. The effects of a 2'-oxygen on sugar-carbon chemical shifts have been examined by comparing the data for 2'-deoxyadenosine, arabinosyladenine and 8:2'-anhydro-8-oxy-9-beta-D-arabinofuranosyladenine. The effects of phosphomonoester groups on base and sugar carbon resonances have been examined and it is noted that these groups cause downfield shifts for C-8 of all cyclonucleotides. Data for the 3':5'-cyclic monophosphate derivative of 8:2'-anhydro-8-thio-9-beta-D-arabinofuranosyladenine suggest that the previous assignments of C-4' and C-3' for nucleoside 3':5'-cyclic monophosphates must be reversed. According to the reversed assignments, it seems that C-3' and C-5' show moderate downfield shifts and C-4' shows a marked upfield shift."}
{"id": "PMID:213273", "title": "Isolation of precursors of cytochrome oxidase from Neurospora crassa: application of subunit-specific antibodies and protein A from Staphylococcus aureus.", "content": "A novel immunological procedure has been applied for the isolation of precursors of cytochrome oxidase. It involves antibodies to individual subunits of the oxidase and protein A from Staphylococcus aureus linked to a Sepharose support. Unassembled (free) 'subunits' as well as a labile complex containing five polypeptide components of the oxidase were isolated from mitochondrial extracts by this technique. The procedure is superior to the previously used double-immuno-precipitation method, because of its quantitative nature, its sensitivity, rapidity and versatility. Thus, sequential titrations of precursor proteins by addition of various subunit-specific immuno-globulins to an individual extract become feasible. Furthermore, the technique is suitable for the isolation of precursors on a large scale. To avoid contamination of the polypeptide preparations with immunoglobulin, the antibodies were covalently coupled to protein A, which had been previously linked to Sepharose. A radioactive preparation of unassembled subunit 1 of cytochrome oxidase was isolated by such a modified support and its cyanogen-bromide-cleavage products were compared to those of subunit 1 obtained from the assembled enzyme.", "contents": "Isolation of precursors of cytochrome oxidase from Neurospora crassa: application of subunit-specific antibodies and protein A from Staphylococcus aureus. A novel immunological procedure has been applied for the isolation of precursors of cytochrome oxidase. It involves antibodies to individual subunits of the oxidase and protein A from Staphylococcus aureus linked to a Sepharose support. Unassembled (free) 'subunits' as well as a labile complex containing five polypeptide components of the oxidase were isolated from mitochondrial extracts by this technique. The procedure is superior to the previously used double-immuno-precipitation method, because of its quantitative nature, its sensitivity, rapidity and versatility. Thus, sequential titrations of precursor proteins by addition of various subunit-specific immuno-globulins to an individual extract become feasible. Furthermore, the technique is suitable for the isolation of precursors on a large scale. To avoid contamination of the polypeptide preparations with immunoglobulin, the antibodies were covalently coupled to protein A, which had been previously linked to Sepharose. A radioactive preparation of unassembled subunit 1 of cytochrome oxidase was isolated by such a modified support and its cyanogen-bromide-cleavage products were compared to those of subunit 1 obtained from the assembled enzyme."}
{"id": "PMID:213274", "title": "Comment on the use of linear free-energy slopes as criteria for distinguishing hydride-ion from hydrogen-atom transfer in reactions of pyridine-nucleotide coenzymes.", "content": "For reductions by dihydropyridines, the slopes of plots of log k vs the standard reduction potential of the dihydropyridine are not direct indicators of whether the rate-determining step is hydride-ion or hydrogen-atom transfer. When there is no substituent effect on the reverse rate, those slopes are independent of mechanism and equal to about (30mV)-1.", "contents": "Comment on the use of linear free-energy slopes as criteria for distinguishing hydride-ion from hydrogen-atom transfer in reactions of pyridine-nucleotide coenzymes. For reductions by dihydropyridines, the slopes of plots of log k vs the standard reduction potential of the dihydropyridine are not direct indicators of whether the rate-determining step is hydride-ion or hydrogen-atom transfer. When there is no substituent effect on the reverse rate, those slopes are independent of mechanism and equal to about (30mV)-1."}
{"id": "PMID:213275", "title": "The reaction of pyruvate with saccharopine dehydrogenase.", "content": "The preceding paper in this journal has reported that pyruvate could be substituted for 2-oxo-glutarate as a substrate of saccharopine dehydrogenase [epsilon-N-(L-glutaryl-2)-L-lysine:NAD oxidoreductase (L-lysine-forming) in the direction of reductive condensation. In the present communication, the kinetic mechanism of saccharopine dehydrogenase reaction with NADH, L-lysine and pyruvate as reactants is reported. The results of initial velocity study, inhibition studies with lysine analogs and a reaction product, NAD+, are consistent with an ordered mechanism with the coenzyme binding first and pyruvate last. The reaction mechanism is at variance with that of the normal reaction in which 2-oxoglutarate is the substrate, in that the order of addition of the amino and  oxo acid substrates is reversed. This fact suggests that there exists a small degree of randomness in the binding of amino and oxo acid substrates. From a product inhibition study, NAD+ was shown to be the last reactant released. Saccharopine [epsilon-N-(L-glutaryl-2)-L-lysine] was found to act as a potent dead-end inhibitor of the condensation reactions (of lysine and 2-oxoglutarate, and of lysine and pyruvate) by forming an abortive E. NADH. saccharopine complex.", "contents": "The reaction of pyruvate with saccharopine dehydrogenase. The preceding paper in this journal has reported that pyruvate could be substituted for 2-oxo-glutarate as a substrate of saccharopine dehydrogenase [epsilon-N-(L-glutaryl-2)-L-lysine:NAD oxidoreductase (L-lysine-forming) in the direction of reductive condensation. In the present communication, the kinetic mechanism of saccharopine dehydrogenase reaction with NADH, L-lysine and pyruvate as reactants is reported. The results of initial velocity study, inhibition studies with lysine analogs and a reaction product, NAD+, are consistent with an ordered mechanism with the coenzyme binding first and pyruvate last. The reaction mechanism is at variance with that of the normal reaction in which 2-oxoglutarate is the substrate, in that the order of addition of the amino and  oxo acid substrates is reversed. This fact suggests that there exists a small degree of randomness in the binding of amino and oxo acid substrates. From a product inhibition study, NAD+ was shown to be the last reactant released. Saccharopine [epsilon-N-(L-glutaryl-2)-L-lysine] was found to act as a potent dead-end inhibitor of the condensation reactions (of lysine and 2-oxoglutarate, and of lysine and pyruvate) by forming an abortive E. NADH. saccharopine complex."}
{"id": "PMID:213276", "title": "Purification and properties of poly(ADP-ribose) polymerase from pig-thymus nuclei.", "content": "The nuclear enzyme poly(ADP-ribose) polymerase has been purified about 9200-fold from pig thymus nuclei with a 46% yield. An aqueous organic solvent system was used for the isolation of the polymerase from nuclei and for its purification by chromatography at sub-zero temperatures. Electrophoretic analysis under both denaturing and non-denaturing conditions revealed a single protein band suggesting that the preparation was homogeneous and that the enzyme is composed of one polypeptide chain. The molecular weight estimated from sodium dodecyl sulphate-/polyacrylamide gel electrophoresis was 63 500 and from gel filtration through columns of Sephadex G-100, 58 000. The enzyme preparation was free from poly(ADP-ribose)-degrading enzymes and from DNA. The purified polymerase showed an absolute requirement for both DNA and histones. The maximal specific activity of the homogeneous preparation measured by the standardized assay, was 20.7 mu mol NAD+ incorporated x min-1 x mg-1 of protein at 37 degree C. Amino-terminal group analysis with dansyl chloride did not reveal a terminal amino acid suggesting that the amino-terminal group may be blocked. In the presence of histones, the Km for NAD+ was 23 micrometer.", "contents": "Purification and properties of poly(ADP-ribose) polymerase from pig-thymus nuclei. The nuclear enzyme poly(ADP-ribose) polymerase has been purified about 9200-fold from pig thymus nuclei with a 46% yield. An aqueous organic solvent system was used for the isolation of the polymerase from nuclei and for its purification by chromatography at sub-zero temperatures. Electrophoretic analysis under both denaturing and non-denaturing conditions revealed a single protein band suggesting that the preparation was homogeneous and that the enzyme is composed of one polypeptide chain. The molecular weight estimated from sodium dodecyl sulphate-/polyacrylamide gel electrophoresis was 63 500 and from gel filtration through columns of Sephadex G-100, 58 000. The enzyme preparation was free from poly(ADP-ribose)-degrading enzymes and from DNA. The purified polymerase showed an absolute requirement for both DNA and histones. The maximal specific activity of the homogeneous preparation measured by the standardized assay, was 20.7 mu mol NAD+ incorporated x min-1 x mg-1 of protein at 37 degree C. Amino-terminal group analysis with dansyl chloride did not reveal a terminal amino acid suggesting that the amino-terminal group may be blocked. In the presence of histones, the Km for NAD+ was 23 micrometer."}
{"id": "PMID:213278", "title": "Mapping the ATP-binding site in the catalytic subunit of adenosine-3':5'-monophosphate-dependent protein kinase. Spatial relationship with the ATP site of the undissociated enzyme.", "content": "A set of 24 ATP analogs modified at various positions of the ATP molecule was used for mapping the ATP-binding site in the free catalytic subunit (C) of cAMP-dependent protein kinase (type I). Ki values for these analogs (of which 23 were shown to be competitive with ATP) were measured and compared with Ki values previously obtained for the same set of analogs upon binding to the undissociated form of the enzyme (R2C2). It was found that modifications at the adenine part of ATP bring about a considerable reduction in affinity between C and the resulting analog. The other parts of the ATP molecule play a less important, though definite, role in the binding of this nucleotide to C. By measuring the effect of each given modification in ATP on its binding to C, and comparing the effect of this modification on the binding of the same analog to R2C2, it was possible to obtain 'specificity profiles' for both forms of the kinase. Using such profiles it is shown that the adenine-binding subsite in C may well coincide with the adenine-binding subsite in R2C2. Two plausible models describing the spatial relationship between the ATP sites in C and R2C2 are proposed.", "contents": "Mapping the ATP-binding site in the catalytic subunit of adenosine-3':5'-monophosphate-dependent protein kinase. Spatial relationship with the ATP site of the undissociated enzyme. A set of 24 ATP analogs modified at various positions of the ATP molecule was used for mapping the ATP-binding site in the free catalytic subunit (C) of cAMP-dependent protein kinase (type I). Ki values for these analogs (of which 23 were shown to be competitive with ATP) were measured and compared with Ki values previously obtained for the same set of analogs upon binding to the undissociated form of the enzyme (R2C2). It was found that modifications at the adenine part of ATP bring about a considerable reduction in affinity between C and the resulting analog. The other parts of the ATP molecule play a less important, though definite, role in the binding of this nucleotide to C. By measuring the effect of each given modification in ATP on its binding to C, and comparing the effect of this modification on the binding of the same analog to R2C2, it was possible to obtain 'specificity profiles' for both forms of the kinase. Using such profiles it is shown that the adenine-binding subsite in C may well coincide with the adenine-binding subsite in R2C2. Two plausible models describing the spatial relationship between the ATP sites in C and R2C2 are proposed."}
{"id": "PMID:213279", "title": "Actin amino-acid sequences. Comparison of actins from calf thymus, bovine brain, and SV40-transformed mouse 3T3 cells with rabbit skeletal muscle actin.", "content": "Actin was purified from calf thymus, bovine brain and SV40-transformed mouse 3T3 cells grown in tissue culture. Isoelectric focusing analysis showed the presence of the two actin polypeptides beta and gamma typical for non-muscle actins in all three actins. Tryptic and thermolytic peptides accounting for the complete amino-acid sequence of the cytoplasmic actins were separated and isolated by preparative fingerprint techniques. All peptides were characterized by amino-acid analysis and compared with the corresponding peptides from rabbit skeletal muscle actin. Peptides which differed in amino-acid composition from the corresponding skeletal muscle actin peptides were subjected to sequence analysis in order to localize the amino-acid replacement. The results obtained show that all three mammalian cytoplasmic actins studied contain the same amino-acid exchanges indicating that mammalian cytoplasmic actins are very similar if not identical in amino-acid sequence. The presence of two different isoelectric species beta and gamma in cytoplasmic actins from higher vertebrates is acccounted for by the isolation of two very similar but not identical amino-terminal peptides in all three actin preparations. The nature of the amino-acid replacements in these two peptides not only accounts for the different isoelectric forms but also shows that beta and gamma cytoplasmic actins are the products of two different structural genes expressed in the same cell. The total number of amino-acid replacements so far detected in the comparison of these cytoplasmic actins and skeletal muscle actin is 25 for the beta chain and 24 for the gamma chain. With the exception of the amino-terminal three or four residues, which are responsible for the isoelectric differences, the replacements do not involve charged amino acids. The exchanges are not randomly distributed. No replacements were detected in regions 18--75 and 299--356 while the regions between residues 2--17 and 259--298 show a high number of replacements. In addition documentation for a few minor revisions of the amino acid sequence of rabbit skeletal muscle actin is provided.", "contents": "Actin amino-acid sequences. Comparison of actins from calf thymus, bovine brain, and SV40-transformed mouse 3T3 cells with rabbit skeletal muscle actin. Actin was purified from calf thymus, bovine brain and SV40-transformed mouse 3T3 cells grown in tissue culture. Isoelectric focusing analysis showed the presence of the two actin polypeptides beta and gamma typical for non-muscle actins in all three actins. Tryptic and thermolytic peptides accounting for the complete amino-acid sequence of the cytoplasmic actins were separated and isolated by preparative fingerprint techniques. All peptides were characterized by amino-acid analysis and compared with the corresponding peptides from rabbit skeletal muscle actin. Peptides which differed in amino-acid composition from the corresponding skeletal muscle actin peptides were subjected to sequence analysis in order to localize the amino-acid replacement. The results obtained show that all three mammalian cytoplasmic actins studied contain the same amino-acid exchanges indicating that mammalian cytoplasmic actins are very similar if not identical in amino-acid sequence. The presence of two different isoelectric species beta and gamma in cytoplasmic actins from higher vertebrates is acccounted for by the isolation of two very similar but not identical amino-terminal peptides in all three actin preparations. The nature of the amino-acid replacements in these two peptides not only accounts for the different isoelectric forms but also shows that beta and gamma cytoplasmic actins are the products of two different structural genes expressed in the same cell. The total number of amino-acid replacements so far detected in the comparison of these cytoplasmic actins and skeletal muscle actin is 25 for the beta chain and 24 for the gamma chain. With the exception of the amino-terminal three or four residues, which are responsible for the isoelectric differences, the replacements do not involve charged amino acids. The exchanges are not randomly distributed. No replacements were detected in regions 18--75 and 299--356 while the regions between residues 2--17 and 259--298 show a high number of replacements. In addition documentation for a few minor revisions of the amino acid sequence of rabbit skeletal muscle actin is provided."}
{"id": "PMID:213280", "title": "Restriction and modification in Bacillus subtilis. Localization of the methylated nucleotide in the BsuRI recognition sequence.", "content": "Calf thymus DNA was methylated in vitro with cell extracts of Bacillus subtilis OG3R (r+m+) and S-adenosyl[Me-3H]methionine. After depurination of the [3H]methylated DNA, the analysis of the pyrimidine dinucleotides revealed the following positions of the methylated nucleosides (indicated by an asterisk) within the BsuRI recognition sequence: 5' dG--dG--dC--dC dC--dC--dG--dG 5'.", "contents": "Restriction and modification in Bacillus subtilis. Localization of the methylated nucleotide in the BsuRI recognition sequence. Calf thymus DNA was methylated in vitro with cell extracts of Bacillus subtilis OG3R (r+m+) and S-adenosyl[Me-3H]methionine. After depurination of the [3H]methylated DNA, the analysis of the pyrimidine dinucleotides revealed the following positions of the methylated nucleosides (indicated by an asterisk) within the BsuRI recognition sequence: 5' dG--dG--dC--dC dC--dC--dG--dG 5'."}
{"id": "PMID:213281", "title": "Mechanism of activation of protein kinase I from rabbit skeletal muscle. The equilibrium parameters of ligand interaction and protein dissociation.", "content": "Protein kinase I from rabbit skeletal muscle binds adenosine 3':5'-monophosphate (cAMP) and ATP with high affinity; cAMP promotes and ATP retards dissociation (activation) of the tetrameric enzyme. The interrelationship of ligand interaction with protein dissociation has been probed by quantitative ligand binding, using the filter assay technique, and by computer simulation of binding curves in terms of Scatchard plots. A comparison of the experimental and computed binding data strongly confirms the supposition that the dimeric regulatory subunit (R2) binds cAMP cooperatively. Mainly from ATP binding it is further concluded that the interaction of the two catalytic subunits with R2 is also strongly cooperative, whereas the binding of ATP to the holoenzyme is non-cooperative. The underlying random model, possessing low-affinity and high-affinity sites not only for ATP but also for cAMP, allows the determination of a minimal set of equilibrium parameters required for description and also an estimation of their magnitude. It further provides a basis for an explanation of the different behaviour of protein kinases I and II reported in the literature.", "contents": "Mechanism of activation of protein kinase I from rabbit skeletal muscle. The equilibrium parameters of ligand interaction and protein dissociation. Protein kinase I from rabbit skeletal muscle binds adenosine 3':5'-monophosphate (cAMP) and ATP with high affinity; cAMP promotes and ATP retards dissociation (activation) of the tetrameric enzyme. The interrelationship of ligand interaction with protein dissociation has been probed by quantitative ligand binding, using the filter assay technique, and by computer simulation of binding curves in terms of Scatchard plots. A comparison of the experimental and computed binding data strongly confirms the supposition that the dimeric regulatory subunit (R2) binds cAMP cooperatively. Mainly from ATP binding it is further concluded that the interaction of the two catalytic subunits with R2 is also strongly cooperative, whereas the binding of ATP to the holoenzyme is non-cooperative. The underlying random model, possessing low-affinity and high-affinity sites not only for ATP but also for cAMP, allows the determination of a minimal set of equilibrium parameters required for description and also an estimation of their magnitude. It further provides a basis for an explanation of the different behaviour of protein kinases I and II reported in the literature."}
{"id": "PMID:213282", "title": "Lymphocyte subpopulations in blood and cerebrospinal fluid from patients with acute Guillain-Barr\u00e9 syndrome.", "content": "The numbers of T and B lymphocytes were determined in blood and cerebrospinal fluid (CSF) from 25 patients with acute Guillain-Barr\u00e9 syndrome and from 30 controls. The relative and absolute number of T lymphocytes in blood was decreased in the patient group (mean 48 +/- 2% and 947 +/- 71/mm3 compared to 66 +/- 2% and 1,381 +/- 93/mm3 in controls). Correspondingly, the number of B lymphocytes was increased (mean 37 +/- 2% and 758 +/- 75/mm3 compared to 25 +/- 2% and 580 +/- 45/mm3 in controls). In the CSF the number of T lymphocytes was increased (85.0 +/- 2.2% compared to 76.9 +/- 2.4% in controls).", "contents": "Lymphocyte subpopulations in blood and cerebrospinal fluid from patients with acute Guillain-Barr\u00e9 syndrome. The numbers of T and B lymphocytes were determined in blood and cerebrospinal fluid (CSF) from 25 patients with acute Guillain-Barr\u00e9 syndrome and from 30 controls. The relative and absolute number of T lymphocytes in blood was decreased in the patient group (mean 48 +/- 2% and 947 +/- 71/mm3 compared to 66 +/- 2% and 1,381 +/- 93/mm3 in controls). Correspondingly, the number of B lymphocytes was increased (mean 37 +/- 2% and 758 +/- 75/mm3 compared to 25 +/- 2% and 580 +/- 45/mm3 in controls). In the CSF the number of T lymphocytes was increased (85.0 +/- 2.2% compared to 76.9 +/- 2.4% in controls)."}
{"id": "PMID:213283", "title": "Latent viruses and Bell's palsy in children.", "content": "4 children with unilateral facial palsy--Bell's palsy (BP)--had serological evidence of primary infection with Epstein-Barr virus (EBV). Concomitant infection with cytomegalovirus (CMV) was demonstrated in 1 child while in all 4 children a rise in antibody titers to an additional one or two viruses was demonstrated. The viruses involved were herpes simplex, CMV and adenovirus which are latent in humans. Immunosuppression induced by EBV and steroid treatment may cause reactivation of these viruses resulting in rise in antibody titers. The need for prolonged serological follow-up for possible reactivation of latent viruses in BP is emphasized.", "contents": "Latent viruses and Bell's palsy in children. 4 children with unilateral facial palsy--Bell's palsy (BP)--had serological evidence of primary infection with Epstein-Barr virus (EBV). Concomitant infection with cytomegalovirus (CMV) was demonstrated in 1 child while in all 4 children a rise in antibody titers to an additional one or two viruses was demonstrated. The viruses involved were herpes simplex, CMV and adenovirus which are latent in humans. Immunosuppression induced by EBV and steroid treatment may cause reactivation of these viruses resulting in rise in antibody titers. The need for prolonged serological follow-up for possible reactivation of latent viruses in BP is emphasized."}
{"id": "PMID:213284", "title": "Night sleep organization in patients with severe hepatic failure. Its modifications after L-dopa treatment.", "content": "20 subjects with severe hepatic failure have been studied by means of all night polygraphic sleep recordings. Base night recordings have been made, as well as registrations after treatment with drugs that are known to improve the clinical conditions of these patients, especially concerning the psychic performances. Base night recordings show sleep disruption, with a large amount of wakefulness at the beginning of the registrations and during the night itself; sleep stages are strongly reduced, especially REM sleep. After L-dopa treatment, these negative patterns are furthermore enhanced and the percentage incidence of the REM stage is very low; nevertheless, this behaviour goes side by side with a light improvement in psychological performances. On the contrary, therapy with lactulose seems to improve the neuropsychiatric state and the sleep organization; as a matter of fact, wakefulness is lower in the night records after lactulose treatment, whilst the percentage incidence of sleep stages tends back toward normality; REM sleep has clearly risen.", "contents": "Night sleep organization in patients with severe hepatic failure. Its modifications after L-dopa treatment. 20 subjects with severe hepatic failure have been studied by means of all night polygraphic sleep recordings. Base night recordings have been made, as well as registrations after treatment with drugs that are known to improve the clinical conditions of these patients, especially concerning the psychic performances. Base night recordings show sleep disruption, with a large amount of wakefulness at the beginning of the registrations and during the night itself; sleep stages are strongly reduced, especially REM sleep. After L-dopa treatment, these negative patterns are furthermore enhanced and the percentage incidence of the REM stage is very low; nevertheless, this behaviour goes side by side with a light improvement in psychological performances. On the contrary, therapy with lactulose seems to improve the neuropsychiatric state and the sleep organization; as a matter of fact, wakefulness is lower in the night records after lactulose treatment, whilst the percentage incidence of sleep stages tends back toward normality; REM sleep has clearly risen."}
{"id": "PMID:213285", "title": "Collagenase isolation and 45Ca efflux studies of human islets of Langerhans.", "content": "22 human pancreases were removed soon after circulatory arrest from donors aged 15--63 years. Part of the pancreas was used for isolation of islets by the collagenase technique. The mean yield +/- SEM, expressed as the number of islets isolated from 4 g pancreas was 79 +/- 15. The yield varied considerably even when the pancreas was removed immediately after circulatory arrest and the histology was normal, and there was no correlation with the age of the donors. The islet content of insulin (ng/microgram dry islet) was 8.5 +/- 1.2 (mean +/- SEM). Isolated islets were loaded with 45Ca in the presence of 20 mM glucose and placed in a perfusion apparatus for further studies of the 45Ca washout. The decrease of washout of radioactivity in Ca2+-deficient medium offers support for the existence of a Ca2+-Ca2+ exchange process. When added in a concentration of 20 mM, glucose tended to stimulate 45Ca efflux in perfusion medium of ordinary ionic composition but inhibited this process when the medium was deficient in Ca2+. Exposure to the calcium ionophore X-537A resulted in immediate stimulation of of 45Ca efflux from human islets as previously observed for islets from rats and mice. This suggests that Ca2+ has a direct regulatory role for insulin release also in humans.", "contents": "Collagenase isolation and 45Ca efflux studies of human islets of Langerhans. 22 human pancreases were removed soon after circulatory arrest from donors aged 15--63 years. Part of the pancreas was used for isolation of islets by the collagenase technique. The mean yield +/- SEM, expressed as the number of islets isolated from 4 g pancreas was 79 +/- 15. The yield varied considerably even when the pancreas was removed immediately after circulatory arrest and the histology was normal, and there was no correlation with the age of the donors. The islet content of insulin (ng/microgram dry islet) was 8.5 +/- 1.2 (mean +/- SEM). Isolated islets were loaded with 45Ca in the presence of 20 mM glucose and placed in a perfusion apparatus for further studies of the 45Ca washout. The decrease of washout of radioactivity in Ca2+-deficient medium offers support for the existence of a Ca2+-Ca2+ exchange process. When added in a concentration of 20 mM, glucose tended to stimulate 45Ca efflux in perfusion medium of ordinary ionic composition but inhibited this process when the medium was deficient in Ca2+. Exposure to the calcium ionophore X-537A resulted in immediate stimulation of of 45Ca efflux from human islets as previously observed for islets from rats and mice. This suggests that Ca2+ has a direct regulatory role for insulin release also in humans."}
{"id": "PMID:213286", "title": "The use of a test for the differential diagnosis of hypercalciuria.", "content": "28 renal stone formers (18 men and 10 women) with idiopathic hypercalciuria (IH) and 27 controls have been subjected to a test proposed for the diagnosis of absorptive, resorptive and renal hypercalciurias. Fasting serum calcium concentration, urinary calcium and cyclic AMP excretion were measured after overnight fasting and an oral load of calcium. Absorptive hypercalciuria was demonstrated in 14 patients. High fasting urinary calcium first suggested resorptive or renal hypercalciurias in 5 other patients, but since fasting urinary calcium was normalized following cellulose phosphate therapy, absorptive hypercalciuria was more likely. Renal hypercalciuria was a possibility in 1 single case. Both fasting and post-load urinary calcium were normal in 7 men and 1 woman. The test did not appear as useful as expected since it was of no diagnostic value in about 30% of the cases and erroneously suggested resorptive or renal hypercalciuria in about 15% of the cases. On the other hand it indicated that absorptive IH is common and renal IH exceptional.", "contents": "The use of a test for the differential diagnosis of hypercalciuria. 28 renal stone formers (18 men and 10 women) with idiopathic hypercalciuria (IH) and 27 controls have been subjected to a test proposed for the diagnosis of absorptive, resorptive and renal hypercalciurias. Fasting serum calcium concentration, urinary calcium and cyclic AMP excretion were measured after overnight fasting and an oral load of calcium. Absorptive hypercalciuria was demonstrated in 14 patients. High fasting urinary calcium first suggested resorptive or renal hypercalciurias in 5 other patients, but since fasting urinary calcium was normalized following cellulose phosphate therapy, absorptive hypercalciuria was more likely. Renal hypercalciuria was a possibility in 1 single case. Both fasting and post-load urinary calcium were normal in 7 men and 1 woman. The test did not appear as useful as expected since it was of no diagnostic value in about 30% of the cases and erroneously suggested resorptive or renal hypercalciuria in about 15% of the cases. On the other hand it indicated that absorptive IH is common and renal IH exceptional."}
{"id": "PMID:213289", "title": "Heterogeneity of cerebral beta-adrenoceptor binding sites in various vertebrate species.", "content": "[3H]-Dihydroalprenolol ([3H]-DHA) binds to cerebral membranes of the frog, chick, rat, mouse, rabbit and human with a dissociation equilibrium constant (KD) of about 1 nM and displays binding characteristics indicative of an interaction with beta-adrenoceptors. However, the maximum number of specific binding sites labelled by this beta-adrenoceptor ligand varies substantially between the species with the chick and mouse having the highest, and the frog the lowest density. The structure--activity relationships of adrenergic agents to inhibit specific [3H]-DHA binding suggests that whereas the membrane sites from all the species had similar affinities for non-selective beta-adrenergic agents, several drugs that have been reported to show selectivity for beta1-adrenoceptors demonstrated considerably higher affinities for mammalian rather than avian or amphibian membrane sites. By this pharmacological criteria it is likely that all the beta-adrenoceptor binding sites in frog and chick cerebral tissue have properties resembling beta2-receptors. However, in mammalian cerebral cortex, evidence is presented that beta1- and beta2-adrenoceptors coexist in a ratio of 70%/30% respectively.", "contents": "Heterogeneity of cerebral beta-adrenoceptor binding sites in various vertebrate species. [3H]-Dihydroalprenolol ([3H]-DHA) binds to cerebral membranes of the frog, chick, rat, mouse, rabbit and human with a dissociation equilibrium constant (KD) of about 1 nM and displays binding characteristics indicative of an interaction with beta-adrenoceptors. However, the maximum number of specific binding sites labelled by this beta-adrenoceptor ligand varies substantially between the species with the chick and mouse having the highest, and the frog the lowest density. The structure--activity relationships of adrenergic agents to inhibit specific [3H]-DHA binding suggests that whereas the membrane sites from all the species had similar affinities for non-selective beta-adrenergic agents, several drugs that have been reported to show selectivity for beta1-adrenoceptors demonstrated considerably higher affinities for mammalian rather than avian or amphibian membrane sites. By this pharmacological criteria it is likely that all the beta-adrenoceptor binding sites in frog and chick cerebral tissue have properties resembling beta2-receptors. However, in mammalian cerebral cortex, evidence is presented that beta1- and beta2-adrenoceptors coexist in a ratio of 70%/30% respectively."}
{"id": "PMID:213290", "title": "Effect of pretreatment with bronchodilator drugs on in vitro responsiveness of guinea pig lung adenylate cyclase.", "content": "Pretreatment of guinea pigs with 5 microgram/kg isoprenaline or 10 microgram/kg salbutamol s.c. thrice daily for 7 days reduced the responsiveness of lung slice and tracheal ring adenylate cyclase to isoprenaline, but not to prostaglandin E1. Pretreatment of guinea pigs with isoprenaline also reduced the sensitivity of tracheal smooth muscle strip adenylate cyclase to isoprenaline. Cross-tolerance developed to noradrenaline in lung slices obtained from guinea pigs pretreated with isoprenaline. Propranolol blocked the response of lung slice adenylate cyclase of control and isoprenaline-pretreated animals to approximately the same degree. The presence of phentolamine in the incubation medium did not affect the reduced sensitivity to isoprenaline. Possible mechanisms of development of tolerance to sympathomimetic bronchodilator drugs are discussed.", "contents": "Effect of pretreatment with bronchodilator drugs on in vitro responsiveness of guinea pig lung adenylate cyclase. Pretreatment of guinea pigs with 5 microgram/kg isoprenaline or 10 microgram/kg salbutamol s.c. thrice daily for 7 days reduced the responsiveness of lung slice and tracheal ring adenylate cyclase to isoprenaline, but not to prostaglandin E1. Pretreatment of guinea pigs with isoprenaline also reduced the sensitivity of tracheal smooth muscle strip adenylate cyclase to isoprenaline. Cross-tolerance developed to noradrenaline in lung slices obtained from guinea pigs pretreated with isoprenaline. Propranolol blocked the response of lung slice adenylate cyclase of control and isoprenaline-pretreated animals to approximately the same degree. The presence of phentolamine in the incubation medium did not affect the reduced sensitivity to isoprenaline. Possible mechanisms of development of tolerance to sympathomimetic bronchodilator drugs are discussed."}
{"id": "PMID:213291", "title": "Presynaptic inhibitory effects of catecholamines on cholinergic transmission in the smooth muscle of the chick stomach.", "content": "In the vagus nerve--smooth muscle preparation isolated from the chick proventriculus, adrenaline, clonidine (10(-8) - 2.5 x 10(-7) M), noradrenaline (10(-7) - 2.5 x 10(-6) M) and dopamine (10(-5) - 10(-4) M) inhibited the contraction induced by low frequency (0.5 Hz) stimulation of the vagus nerve, but they did not inhibit the contraction elicited by acetylcholine (5 x 10(-8) - 5 x 10(-7) M). The concentration producing 50% inhibition was 10(-7) M for adrenaline and clonidine, 10(-6) M for noradrenaline, and 5 x 10(-5) M for dopamine. Isoproterenol (5 x 10(-8) - 5 x 10(-7) M) inhibited the responses induced by both stimulation of the vagus nerve and acetylcholine. The inhibitory effects of the catecholamine and clonidine were blocked by phentolamine (2.7 x 10(-6) M) but not by 5-(3-tert-Butylamino-2-hydroxy)-propoxy-3, 4-dihydrocarbostyril hydrochloride (OPC 1085) which blocked the effect of isoproterenol. It is suggested that presynaptic alpha-receptors are present in the myenteric plexus of the chick proventriculus, and that the catecholamines and clonidine exert their inhibitory effects on cholinergic transmission via these receptors.", "contents": "Presynaptic inhibitory effects of catecholamines on cholinergic transmission in the smooth muscle of the chick stomach. In the vagus nerve--smooth muscle preparation isolated from the chick proventriculus, adrenaline, clonidine (10(-8) - 2.5 x 10(-7) M), noradrenaline (10(-7) - 2.5 x 10(-6) M) and dopamine (10(-5) - 10(-4) M) inhibited the contraction induced by low frequency (0.5 Hz) stimulation of the vagus nerve, but they did not inhibit the contraction elicited by acetylcholine (5 x 10(-8) - 5 x 10(-7) M). The concentration producing 50% inhibition was 10(-7) M for adrenaline and clonidine, 10(-6) M for noradrenaline, and 5 x 10(-5) M for dopamine. Isoproterenol (5 x 10(-8) - 5 x 10(-7) M) inhibited the responses induced by both stimulation of the vagus nerve and acetylcholine. The inhibitory effects of the catecholamine and clonidine were blocked by phentolamine (2.7 x 10(-6) M) but not by 5-(3-tert-Butylamino-2-hydroxy)-propoxy-3, 4-dihydrocarbostyril hydrochloride (OPC 1085) which blocked the effect of isoproterenol. It is suggested that presynaptic alpha-receptors are present in the myenteric plexus of the chick proventriculus, and that the catecholamines and clonidine exert their inhibitory effects on cholinergic transmission via these receptors."}
{"id": "PMID:213292", "title": "Effects of diethyldithiocarbamate and fusaric acid upon memory storage processes in rats.", "content": "Diethyldithiocarbamate (DDC) and fusaric acid (FA), administered immediately posttraining, disrupted retention performance of rats trained on a one-trial inhibitory avoidance task. Posttraining DDC disrupted retention performance if the treatment was delayed up to at least 24 h (but not 72 h) after training. A single DDC injection also disrupted retention performance if the treatment was administered up to 10 days prior to training. The effects of DDC and FA upon several neurobiological measures were also investigated. Amnestic doses of DDC influence brain and adrenal catecholamine levels, brain electrographic activity and hippocampal Timm's staining. On the other hand, amnestic doses of FA only affected catecholamine levels. The amnestic effects of DDC were dissociated from brain seizure activity produced by DDC. The effects of DDC and FA upon retention may have been related to the drugs' effects upon catecholamine systems, but the bleaching by DDC of Timm's staining could reflect additional processes involved in DDC's effects upon retention. As opposed to the more widespread effects of DDC, FA's relative lack of effect upon other neurobiological measures more strongly supports a catecholaminergic interpretation for its effect upon retention.", "contents": "Effects of diethyldithiocarbamate and fusaric acid upon memory storage processes in rats. Diethyldithiocarbamate (DDC) and fusaric acid (FA), administered immediately posttraining, disrupted retention performance of rats trained on a one-trial inhibitory avoidance task. Posttraining DDC disrupted retention performance if the treatment was delayed up to at least 24 h (but not 72 h) after training. A single DDC injection also disrupted retention performance if the treatment was administered up to 10 days prior to training. The effects of DDC and FA upon several neurobiological measures were also investigated. Amnestic doses of DDC influence brain and adrenal catecholamine levels, brain electrographic activity and hippocampal Timm's staining. On the other hand, amnestic doses of FA only affected catecholamine levels. The amnestic effects of DDC were dissociated from brain seizure activity produced by DDC. The effects of DDC and FA upon retention may have been related to the drugs' effects upon catecholamine systems, but the bleaching by DDC of Timm's staining could reflect additional processes involved in DDC's effects upon retention. As opposed to the more widespread effects of DDC, FA's relative lack of effect upon other neurobiological measures more strongly supports a catecholaminergic interpretation for its effect upon retention."}
{"id": "PMID:213293", "title": "Development of sympathetic nerve--muscle transmission in chick.", "content": "The development of sympathetic nerve--muscle transmission was investigated pharmacologically by using the nerve-expansor secundariorum muscle preparation of 2- to 35-day-old chicks. The nerve-induced muscle contraction was not affected by atropine and neostigmine after hatch but was slightly depressed by phentolamine and completely depressed by guanethidine. Since the responsiveness of the muscle to some adrenomimetic drugs remained constant after hatch, adrenergic receptor function does not change during development. The nerve-induced muscle response was scarcely influenced by cocaine or reserpine in neonatal chick while it was potentiated by cocaine and changed by reserpine in mature chicks. These results suggest that cocaine- and reserpine-sensitive mechanisms gradually develop in sympathetic nerve function after hatch. The presence of a potentiating effect of cocaine on the nerve-induced muscle response in dimethylphenylpiperazinium-treated neonatal chick suggests that the development of sympathetic nerve function is regulated by nerve activity itself.", "contents": "Development of sympathetic nerve--muscle transmission in chick. The development of sympathetic nerve--muscle transmission was investigated pharmacologically by using the nerve-expansor secundariorum muscle preparation of 2- to 35-day-old chicks. The nerve-induced muscle contraction was not affected by atropine and neostigmine after hatch but was slightly depressed by phentolamine and completely depressed by guanethidine. Since the responsiveness of the muscle to some adrenomimetic drugs remained constant after hatch, adrenergic receptor function does not change during development. The nerve-induced muscle response was scarcely influenced by cocaine or reserpine in neonatal chick while it was potentiated by cocaine and changed by reserpine in mature chicks. These results suggest that cocaine- and reserpine-sensitive mechanisms gradually develop in sympathetic nerve function after hatch. The presence of a potentiating effect of cocaine on the nerve-induced muscle response in dimethylphenylpiperazinium-treated neonatal chick suggests that the development of sympathetic nerve function is regulated by nerve activity itself."}
{"id": "PMID:213294", "title": "Enkephalin-induced dilatation of pial arteries in vitro probably mediated by opiate receptors.", "content": "Feline pial arteries in an actively contracted state were dilated in a dose dependent manner by enkephalins and morphine in vitro. This vasodilatation was blocked by naloxone suggesting the presence of opiate receptors in the vessel walls.", "contents": "Enkephalin-induced dilatation of pial arteries in vitro probably mediated by opiate receptors. Feline pial arteries in an actively contracted state were dilated in a dose dependent manner by enkephalins and morphine in vitro. This vasodilatation was blocked by naloxone suggesting the presence of opiate receptors in the vessel walls."}
{"id": "PMID:213295", "title": "Effects of SQ 14,225, an orally active inhibitor of angiotensin-converting enzyme on blood pressure, heart rate and plasma renin activity of conscious normotensive dogs.", "content": "Oral administration of SQ 14,225 (0.03--3 mg/kg) to conscious normotensive dogs caused inhibition of the pressor response to intravenously administered angiotensin I (AI), the duration of which was dose-dependent. All doses of 0.1 mg/kg or greater caused 85--95% inhibition 30 min after administration whereas 0.03 mg/kg produced only a 25% inhibition. Pressor responses to angiotensin II (AII) were not similarly inhibited. Blood pressure was moderately reduced in a dose-related manner and followed the same pattern as inhibition of the AI pressor responses. The maximum change occurred after 1.0 mg/kg with only a more rapid onset occurring after the 3.0 mg/kg dose. Heart rate was not appreciably changed. SQ 14,225 also increased plasma renin activity (PRA), the levels and duration of which were dose-related. These data indicate that SQ 14,225 is an orally effective, potent inhibitor of angiotensin I-converting enzyme (ACE) in dogs. It appears that in mongrel dogs, ACE inhibition results in a slight to moderate reduction in blood pressure and an increase in PRA.", "contents": "Effects of SQ 14,225, an orally active inhibitor of angiotensin-converting enzyme on blood pressure, heart rate and plasma renin activity of conscious normotensive dogs. Oral administration of SQ 14,225 (0.03--3 mg/kg) to conscious normotensive dogs caused inhibition of the pressor response to intravenously administered angiotensin I (AI), the duration of which was dose-dependent. All doses of 0.1 mg/kg or greater caused 85--95% inhibition 30 min after administration whereas 0.03 mg/kg produced only a 25% inhibition. Pressor responses to angiotensin II (AII) were not similarly inhibited. Blood pressure was moderately reduced in a dose-related manner and followed the same pattern as inhibition of the AI pressor responses. The maximum change occurred after 1.0 mg/kg with only a more rapid onset occurring after the 3.0 mg/kg dose. Heart rate was not appreciably changed. SQ 14,225 also increased plasma renin activity (PRA), the levels and duration of which were dose-related. These data indicate that SQ 14,225 is an orally effective, potent inhibitor of angiotensin I-converting enzyme (ACE) in dogs. It appears that in mongrel dogs, ACE inhibition results in a slight to moderate reduction in blood pressure and an increase in PRA."}
{"id": "PMID:213296", "title": "Chronic antihypertensive effects of captopril (SQ 14,225), an orally active angiotensin I-converting enzyme inhibitor, in conscious 2-kidney renal hypertensive rats.", "content": "Indirect systolic blood pressure (SBP) was monitored in 9 groups of 15 male conscious 2-kidney renal hypertensive rats (RHR) for over 6 months. Daily oral dosing with captopril (SQ 14,225, D-3-mercapto-2-methylpropanoyl-L-proline, 30 mg/kg), an orally active angiotensin I-converting enzyme inhibitor, lowered SBP 30--50 MM Hg during this period. Withdrawal of captopril for 5 days at 1, 3 and 6 months resulted in gradual return of SBP to control levels without overshoot. Resumption of dosage with captopril again decreased SBP. Daily oral dosing with hydrochlorothiazide (HCTZ, 6 mg/kg/day) alone for 6 months had little or no effect on SBP, but increased the antihypertensive effect of captopril. Daily oral dosing with hydralazine (6 mg/kg) caused an initial marked antihypertensive effect greater than that of captopril but almost complete tolerance developed within 4 weeks of dosing. Highest survival rates occurred in RHR treated with captopril plus HCTZ. In four other similarly treated groups of RHR and normotensive rats (NR), least cardiac hypertrophy and highest plasma renin activity occurred in captopril-treated animals compared with vehicle-treated controls. Plasma renin activity was about 2 to 4 fold higher in the rats dosed with captopril compared with vehicle-treated rats. Heart weight/body weight ratios, initially higher in the two RHR groups compared to NR, decreased only in the captopril treated group to or near those of the NR groups. These results indicate that chronic treatment with captopril decreased SBP and cardiac weights of RHR, and that HCTZ, or possibly other diuretics, can augment the antihypertensive effect of captopril while having little or no effect by themselves.", "contents": "Chronic antihypertensive effects of captopril (SQ 14,225), an orally active angiotensin I-converting enzyme inhibitor, in conscious 2-kidney renal hypertensive rats. Indirect systolic blood pressure (SBP) was monitored in 9 groups of 15 male conscious 2-kidney renal hypertensive rats (RHR) for over 6 months. Daily oral dosing with captopril (SQ 14,225, D-3-mercapto-2-methylpropanoyl-L-proline, 30 mg/kg), an orally active angiotensin I-converting enzyme inhibitor, lowered SBP 30--50 MM Hg during this period. Withdrawal of captopril for 5 days at 1, 3 and 6 months resulted in gradual return of SBP to control levels without overshoot. Resumption of dosage with captopril again decreased SBP. Daily oral dosing with hydrochlorothiazide (HCTZ, 6 mg/kg/day) alone for 6 months had little or no effect on SBP, but increased the antihypertensive effect of captopril. Daily oral dosing with hydralazine (6 mg/kg) caused an initial marked antihypertensive effect greater than that of captopril but almost complete tolerance developed within 4 weeks of dosing. Highest survival rates occurred in RHR treated with captopril plus HCTZ. In four other similarly treated groups of RHR and normotensive rats (NR), least cardiac hypertrophy and highest plasma renin activity occurred in captopril-treated animals compared with vehicle-treated controls. Plasma renin activity was about 2 to 4 fold higher in the rats dosed with captopril compared with vehicle-treated rats. Heart weight/body weight ratios, initially higher in the two RHR groups compared to NR, decreased only in the captopril treated group to or near those of the NR groups. These results indicate that chronic treatment with captopril decreased SBP and cardiac weights of RHR, and that HCTZ, or possibly other diuretics, can augment the antihypertensive effect of captopril while having little or no effect by themselves."}
{"id": "PMID:213297", "title": "Cerebral ventricular infusion of excess calcium in the rat: effects on sleep states, behavior and cortical EEG.", "content": "Sleep and behavior of the rat were recorded during cerebroventricular infusion of artificial cerebrospinal fluid (aCSF) containing regular or excess concentrations of calcium. Three different types of aCSF were used for control infusions. Depending on the ionic composition, paradoxical sleep (PS) was reduced by 6--52% during a 1-h aCSF infusion period, whereas the total amount of sleep was not altered. The depression of PS by aCSF could be prevented by increasing the concentration of Ca in the infusate by a factor of 2--5 (2.6--9.1 mM). Infusions of high concentrations of Ca (9.1--54.6 mM) caused feeding and wet-dog shakes. A slow-wave cortical EEG pattern prevailed during feeding elicited by either infusion of excess Ca or systemic administration of a small dose of pentobarbital. It is concluded (a) that the ionic composition of the CSF may selectively influence the occurrence of a sleep state, and (b) that Ca-induced feeding may be related to a covert sedative action of this cation.", "contents": "Cerebral ventricular infusion of excess calcium in the rat: effects on sleep states, behavior and cortical EEG. Sleep and behavior of the rat were recorded during cerebroventricular infusion of artificial cerebrospinal fluid (aCSF) containing regular or excess concentrations of calcium. Three different types of aCSF were used for control infusions. Depending on the ionic composition, paradoxical sleep (PS) was reduced by 6--52% during a 1-h aCSF infusion period, whereas the total amount of sleep was not altered. The depression of PS by aCSF could be prevented by increasing the concentration of Ca in the infusate by a factor of 2--5 (2.6--9.1 mM). Infusions of high concentrations of Ca (9.1--54.6 mM) caused feeding and wet-dog shakes. A slow-wave cortical EEG pattern prevailed during feeding elicited by either infusion of excess Ca or systemic administration of a small dose of pentobarbital. It is concluded (a) that the ionic composition of the CSF may selectively influence the occurrence of a sleep state, and (b) that Ca-induced feeding may be related to a covert sedative action of this cation."}
{"id": "PMID:213298", "title": "Negative chronotropic action of cyclic AMP on the fetal rat heart in organ culture.", "content": "Dibutyryl cyclic AMP and cyclic AMP in a DMSO medium were administered to the fetal rat heart in organ culture. Changes in heart rate were observed. Dibutyryl cyclic AMP in concentrations of 5 X 10(-5) M and 1 X 10(-4) M produced significant negative chronotropism. At a concentration of 1 X 10(-3) M, cyclic AMP in a 3% or 0.5% DMSO medium produced significant negative chronotropism. These data were compared with other studies. The negative chronotropic action of cyclic AMP and its dibutyryl derivative are evidence against the involvement of cyclic AMP in positive cardiac chronotropism.", "contents": "Negative chronotropic action of cyclic AMP on the fetal rat heart in organ culture. Dibutyryl cyclic AMP and cyclic AMP in a DMSO medium were administered to the fetal rat heart in organ culture. Changes in heart rate were observed. Dibutyryl cyclic AMP in concentrations of 5 X 10(-5) M and 1 X 10(-4) M produced significant negative chronotropism. At a concentration of 1 X 10(-3) M, cyclic AMP in a 3% or 0.5% DMSO medium produced significant negative chronotropism. These data were compared with other studies. The negative chronotropic action of cyclic AMP and its dibutyryl derivative are evidence against the involvement of cyclic AMP in positive cardiac chronotropism."}
{"id": "PMID:213299", "title": "Some clinical and epizootological observations of infectious sialoadenitis in rats.", "content": "Epizootological and clinical observation was made of infectious sialoadenitis ocurring at a rat facility. The disease occurred mostly among animals 8 to 64 weeks of age without specific relevance with sex and age, and clinical signs disappeared within 5 days after the onset. Morbidity rates and duration of epizootics ranged from 13 to 100% and from 5 to 32 days, respectively. Most rats having severe clinical signs of sialoadenitis showed decrease in food uptake, body weight loss and remarkable disorders of estrous cycles.", "contents": "Some clinical and epizootological observations of infectious sialoadenitis in rats. Epizootological and clinical observation was made of infectious sialoadenitis ocurring at a rat facility. The disease occurred mostly among animals 8 to 64 weeks of age without specific relevance with sex and age, and clinical signs disappeared within 5 days after the onset. Morbidity rates and duration of epizootics ranged from 13 to 100% and from 5 to 32 days, respectively. Most rats having severe clinical signs of sialoadenitis showed decrease in food uptake, body weight loss and remarkable disorders of estrous cycles."}
{"id": "PMID:213316", "title": "Central receptor sites for angiotensin-induced drinking: a critical review.", "content": "A review of proposed sites of the dipsogenic action of angiotensin II is presented. Techniques used for such localization are critically discussed, and it is suggested that convergence of evidence from several different experimental techniques is required for localization of dipsogenic receptors. Loci suggested as such sites of action include the preoptic regions, the subfornical organ, and the tissue proximal to the optic recess of the third ventricle, including the organum vasculosum laminae terminalis. Current evidence suggests that there are at least two loci within the forebrain that possess dipsogenic receptors for angiotensin II.", "contents": "Central receptor sites for angiotensin-induced drinking: a critical review. A review of proposed sites of the dipsogenic action of angiotensin II is presented. Techniques used for such localization are critically discussed, and it is suggested that convergence of evidence from several different experimental techniques is required for localization of dipsogenic receptors. Loci suggested as such sites of action include the preoptic regions, the subfornical organ, and the tissue proximal to the optic recess of the third ventricle, including the organum vasculosum laminae terminalis. Current evidence suggests that there are at least two loci within the forebrain that possess dipsogenic receptors for angiotensin II."}
{"id": "PMID:213317", "title": "Central neural pathways for angiotensin-induced thirst.", "content": "Evidence is reviewed implicating the preoptic region in angiotensin-induced thirst. The most responsive area according to results obtained with behavioral, electrophysiological, and autoradiographic mapping techniques is at the caudal border of the medial preoptic region and rostral border of the anterior hypothalamus. The neural pathway from this preoptic site for angiotensin-induced thirst extends along the medial forebrain bundle through the midlateral hypothalamus to the paramedial midbrain tegmentum and to an area ventrolateral to the central gray. Lesions of this pathway in the midlateral hypothalamus and rostral midbrain significantly attenuated drinking induced by microinjections of angiotensin II into the preoptic area but did not disrupt water intake induced by microinjections of angiotensin II into the subfornical organ or cerebral ventricles. Although the efferent pathways from angiotensin-receptive sites in the subfornical organ and cerebral ventricles are unknown, it appears from these observations that the medial forebrain bundle is not involved. Lesions of the medial forebrain bundle-lateral hypothalamus also do not disrupt drinking induced by microinjections of hypertonic saline into the preoptic region although lesions placed 1 mm further lateral do. Since fat lateral hypothalamic lesions are without effect on drinking induced by centrally administered angiotensin II, this suggests that intracellular and extracellular thirst signals are subserved by separate neural pathways in the hypothalamus.", "contents": "Central neural pathways for angiotensin-induced thirst. Evidence is reviewed implicating the preoptic region in angiotensin-induced thirst. The most responsive area according to results obtained with behavioral, electrophysiological, and autoradiographic mapping techniques is at the caudal border of the medial preoptic region and rostral border of the anterior hypothalamus. The neural pathway from this preoptic site for angiotensin-induced thirst extends along the medial forebrain bundle through the midlateral hypothalamus to the paramedial midbrain tegmentum and to an area ventrolateral to the central gray. Lesions of this pathway in the midlateral hypothalamus and rostral midbrain significantly attenuated drinking induced by microinjections of angiotensin II into the preoptic area but did not disrupt water intake induced by microinjections of angiotensin II into the subfornical organ or cerebral ventricles. Although the efferent pathways from angiotensin-receptive sites in the subfornical organ and cerebral ventricles are unknown, it appears from these observations that the medial forebrain bundle is not involved. Lesions of the medial forebrain bundle-lateral hypothalamus also do not disrupt drinking induced by microinjections of hypertonic saline into the preoptic region although lesions placed 1 mm further lateral do. Since fat lateral hypothalamic lesions are without effect on drinking induced by centrally administered angiotensin II, this suggests that intracellular and extracellular thirst signals are subserved by separate neural pathways in the hypothalamus."}
{"id": "PMID:213318", "title": "Oxygen metabolism and the microbicidal activity of macrophages.", "content": "Like neutrophils, phagocytizing macrophages undergo a \"respiratory burst\" in which significant quantities of oxygen are drawn into the cell. The consumed oxygen is not used in oxidative phosphorylation but, rather, in the formation of superoxide anion (O2) and H2O2. These oxygen metabolites and the products of their interaction, in particular hydroxyl radical (OH), have been implicated in the killing of ingested bacteria by neutrophils. Their role in macrophage microbicidal activity has not been fully defined. However, activated macrophages, which mediate increased resistance to infection in vivo, have a markedly increased capacity to generate O2 and H2O2 in vitro when stimulated by phagocytosis or surface perturbation. The enhanced capacity of activated macrophages to generate highly reactive oxygen metabolites during phagocytosis could contribute to the improved microbicidal and tumoricidal activity of these cells.", "contents": "Oxygen metabolism and the microbicidal activity of macrophages. Like neutrophils, phagocytizing macrophages undergo a \"respiratory burst\" in which significant quantities of oxygen are drawn into the cell. The consumed oxygen is not used in oxidative phosphorylation but, rather, in the formation of superoxide anion (O2) and H2O2. These oxygen metabolites and the products of their interaction, in particular hydroxyl radical (OH), have been implicated in the killing of ingested bacteria by neutrophils. Their role in macrophage microbicidal activity has not been fully defined. However, activated macrophages, which mediate increased resistance to infection in vivo, have a markedly increased capacity to generate O2 and H2O2 in vitro when stimulated by phagocytosis or surface perturbation. The enhanced capacity of activated macrophages to generate highly reactive oxygen metabolites during phagocytosis could contribute to the improved microbicidal and tumoricidal activity of these cells."}
{"id": "PMID:213320", "title": "Inhibition of ovarian luteinizing hormone (LH) and follicle-stimulating hormone receptor levels with an LH-releasing hormone agonist during the estrous cycle in the rat.", "content": "A single injection of the luteinizing hormone (LH)-releasing hormone (LHRH) agonist [D-Ala6,des-Gly-NH2(10)]LHRH ethylamide to female rats on diestrus I produced a marked reduction in ovarian LH/human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) receptor levels, uterine weight, and plasma progesterone levels measured 2 days later on expected proestrus. A maximal inhibitory effect was seen after a dose of only 40 ng of the peptide. No consistent effect of the LHRH analog was seen on ovarian prolactin receptors. When the analog was injected on day 7 of pregnancy, the inhibition of ovarian LH/hCG receptors was of shorter duration and was much less sensitive than that in nonpregnant animals. These data indicate that ovarian LH and FSH receptors levels are highly sensitive to changes in endogenous gonadotropin secretion and suggest that the gonadotropin surge occurring spontaneously on proestrus may play an important role in the regulation of ovarian gonadotropin receptors during the estrous cycle.", "contents": "Inhibition of ovarian luteinizing hormone (LH) and follicle-stimulating hormone receptor levels with an LH-releasing hormone agonist during the estrous cycle in the rat. A single injection of the luteinizing hormone (LH)-releasing hormone (LHRH) agonist [D-Ala6,des-Gly-NH2(10)]LHRH ethylamide to female rats on diestrus I produced a marked reduction in ovarian LH/human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) receptor levels, uterine weight, and plasma progesterone levels measured 2 days later on expected proestrus. A maximal inhibitory effect was seen after a dose of only 40 ng of the peptide. No consistent effect of the LHRH analog was seen on ovarian prolactin receptors. When the analog was injected on day 7 of pregnancy, the inhibition of ovarian LH/hCG receptors was of shorter duration and was much less sensitive than that in nonpregnant animals. These data indicate that ovarian LH and FSH receptors levels are highly sensitive to changes in endogenous gonadotropin secretion and suggest that the gonadotropin surge occurring spontaneously on proestrus may play an important role in the regulation of ovarian gonadotropin receptors during the estrous cycle."}
{"id": "PMID:213326", "title": "Prostaglandins and opioids.", "content": "In guinea-pig small intestine, rat brain in vitro and neuroblastomaXglioma hybrid cells, opioids specifically inhibit the action of E prostaglandins. In the whole rat, E prostaglandins, administered centrally, antagonize the antinociceptive action of morphine. E prostaglandins also antangonize the induction of opioid tolerant/dependence. In turn, tolerance/dependent preparations respond with added intensity to E prostaglandins. The antagonism between opioids and E prostaglandins does not occur at the opioid receptor; but, certainly in some preparations and probably in others, this antagonism occurs at the coupling or catalytic unit of a neuronal adenylate cyclase that opioids inhibit and E prostaglandins stimulate. The proposition that antagonism of E prostaglandin at appropriate neurons in the brain is part of the natural mechanism of opioid analgesia remains possible, but unproven, and is worth continued investigation.", "contents": "Prostaglandins and opioids. In guinea-pig small intestine, rat brain in vitro and neuroblastomaXglioma hybrid cells, opioids specifically inhibit the action of E prostaglandins. In the whole rat, E prostaglandins, administered centrally, antagonize the antinociceptive action of morphine. E prostaglandins also antangonize the induction of opioid tolerant/dependence. In turn, tolerance/dependent preparations respond with added intensity to E prostaglandins. The antagonism between opioids and E prostaglandins does not occur at the opioid receptor; but, certainly in some preparations and probably in others, this antagonism occurs at the coupling or catalytic unit of a neuronal adenylate cyclase that opioids inhibit and E prostaglandins stimulate. The proposition that antagonism of E prostaglandin at appropriate neurons in the brain is part of the natural mechanism of opioid analgesia remains possible, but unproven, and is worth continued investigation."}
{"id": "PMID:213332", "title": "The effect of propranolol on hypoglycaemia. Observations in five insulinoma patients.", "content": "Five hypoglycaemic hyperinsulinaemic patients (three with proven benign insulinoma, one with proven metastasizing insulinoma, one with probable insulinoma not found at surgery) were treated with propranolol for a variable time ranging from two weeks to one year. Three patients showed favourable clinical results and a significant increase of the mean basal blood glucose level was found while two patients showed no improvement of the frequency of neuroglycopenic episodes and no significant increase of their mean blood glucose level. No patient showed a significant decrease in mean basal IRI concentration. A decrease of insulinaemic responses was observed during oral and intravenous glucose tolerance tests, a prolonged fast, and tolbutamide and glucagon tests performed in some patients. The results suggest that propranolol may induce in certain patients an improvement of basal clinical status through not understood effects (probably hepatic), which leave the peripheral concentrations of insulin unchanged, whereas inhibition of insulin secretion may represent the main way by which the improvement of metabolic situation during physiological or pharmacological stimulation may have been achieved.", "contents": "The effect of propranolol on hypoglycaemia. Observations in five insulinoma patients. Five hypoglycaemic hyperinsulinaemic patients (three with proven benign insulinoma, one with proven metastasizing insulinoma, one with probable insulinoma not found at surgery) were treated with propranolol for a variable time ranging from two weeks to one year. Three patients showed favourable clinical results and a significant increase of the mean basal blood glucose level was found while two patients showed no improvement of the frequency of neuroglycopenic episodes and no significant increase of their mean blood glucose level. No patient showed a significant decrease in mean basal IRI concentration. A decrease of insulinaemic responses was observed during oral and intravenous glucose tolerance tests, a prolonged fast, and tolbutamide and glucagon tests performed in some patients. The results suggest that propranolol may induce in certain patients an improvement of basal clinical status through not understood effects (probably hepatic), which leave the peripheral concentrations of insulin unchanged, whereas inhibition of insulin secretion may represent the main way by which the improvement of metabolic situation during physiological or pharmacological stimulation may have been achieved."}
{"id": "PMID:213333", "title": "Relative insensitivity to glucagon of sterol synthesis in cultured rat aortic smooth muscle cells. Effect of dibutyryl cyclic AMP.", "content": "The smooth muscle cell plays an important role in the process of atherogenesis. In these experiments the effect of glucagon and dibutyryl cyclic AMP on sterol synthesis in cultured rat arterial smooth muscle cells was studied. Glucagon in concentrations of 1 X 10(-9) mol/l inhibited the incorporation of sodium (2(-14)C)acetate into non-saponifiable lipids and digitonin precipitable sterols but lower concentrations of glucagon had no effect. In cells which were exposed to serum, dibutyryl cyclic AMP also resulted in a decrease in the incorporation of labelled acetate into sterols but when the cells were grown in serum free medium, dibutyryl cyclic AMP had no inhibitory effect on sterol synthesis. These results provide further evidence that sterol metabolism in arterial smooth cells may be influenced by hormones but suggest that glucagon is relatively less important than insulin in this respect.", "contents": "Relative insensitivity to glucagon of sterol synthesis in cultured rat aortic smooth muscle cells. Effect of dibutyryl cyclic AMP. The smooth muscle cell plays an important role in the process of atherogenesis. In these experiments the effect of glucagon and dibutyryl cyclic AMP on sterol synthesis in cultured rat arterial smooth muscle cells was studied. Glucagon in concentrations of 1 X 10(-9) mol/l inhibited the incorporation of sodium (2(-14)C)acetate into non-saponifiable lipids and digitonin precipitable sterols but lower concentrations of glucagon had no effect. In cells which were exposed to serum, dibutyryl cyclic AMP also resulted in a decrease in the incorporation of labelled acetate into sterols but when the cells were grown in serum free medium, dibutyryl cyclic AMP had no inhibitory effect on sterol synthesis. These results provide further evidence that sterol metabolism in arterial smooth cells may be influenced by hormones but suggest that glucagon is relatively less important than insulin in this respect."}
{"id": "PMID:213334", "title": "Viral studies in streptozotocin-induced pancreatic insulitis.", "content": "Multiple injections of streptozotocin to Charles River (CD-1) Laboratory mice resulted in a syndrome characterised by diabetes mellitus, insulitis and the induction of endogenous type C viruses in pancreatic beta cells. Within one week after the completion of five intraperitoneal injections of streptozotocin, the CD-1 mice exhibited irreversible hyperglycaemia and insulinopaenia. Light microscopic studies of pancreata from mice sacrificed at this time demonstrated insulitis and beta cell necrosis. Electron microscopic studies revealed spherical and atypical cylindrical type C viruses and occasional clusters of intracisternal type A viruses exclusively within beta cells. To clarify the identification of the type C viruses and their role in the genesis of the insulitis, type C virus specific antigens were identified within islet cells by immune fluorescence at various intervals after streptozotocin administration. Immune fluorescence studies demonstrated the presence of type C virus antigens within islets from streptozotocin treated mice but not in buffer-injected controls. Time course studies suggested that type C virus induction may precede the appearance of insulitis by two days and that insulitis is consistently accompanied by the presence of virus positive islet cells.", "contents": "Viral studies in streptozotocin-induced pancreatic insulitis. Multiple injections of streptozotocin to Charles River (CD-1) Laboratory mice resulted in a syndrome characterised by diabetes mellitus, insulitis and the induction of endogenous type C viruses in pancreatic beta cells. Within one week after the completion of five intraperitoneal injections of streptozotocin, the CD-1 mice exhibited irreversible hyperglycaemia and insulinopaenia. Light microscopic studies of pancreata from mice sacrificed at this time demonstrated insulitis and beta cell necrosis. Electron microscopic studies revealed spherical and atypical cylindrical type C viruses and occasional clusters of intracisternal type A viruses exclusively within beta cells. To clarify the identification of the type C viruses and their role in the genesis of the insulitis, type C virus specific antigens were identified within islet cells by immune fluorescence at various intervals after streptozotocin administration. Immune fluorescence studies demonstrated the presence of type C virus antigens within islets from streptozotocin treated mice but not in buffer-injected controls. Time course studies suggested that type C virus induction may precede the appearance of insulitis by two days and that insulitis is consistently accompanied by the presence of virus positive islet cells."}
{"id": "PMID:213336", "title": "Cellular injury of adrenocorticotropic pituitary tumor (AtT-20) by corticosteroid in mice.", "content": "A transplantable ACTH-secreting pituitary tumor (AtT-20) in mice was studied for its growth in relation to adrenocortical steroid. The latency of transplanted tumor in LAF-1 mice with 10(6) tumor cells was about 2 weeks in adrenalectomized and in intact mice. In the former, however, tumor size reached 1.5 cm in diameter within 1 month, while it remained about 0.5 cm in the latter. Macroscopic and microscopic observation revealed that the tumor grafted in intact mice showed massive necrosis, leaving minimum intact tumor cells among necrotic foci. In contrast, the tumor grafted in adrenalectomized mice was healthy, soft, and showed adenomatous structure. It is concluded that excess of adrenocortical steroid produced in the grafted AtT-20 was inhibitory for the growth of transplanted tumor and removal of the adrenal glands was good for growth and survival of transplanted tumor. For the assessment of direct effect of adrenal steroid on AtT-20 cells, incorporation of 3H-thymidine in cultured AtT-20 cells was examined in a medium supplemented with glucocorticoid hormone. The autoradiographic study indicated that the inhibition of 3H-thymidine uptake was demonstrated at 24 hr after incubation with steroid and labeled cells were barely detectable on 3rd and 5th day.", "contents": "Cellular injury of adrenocorticotropic pituitary tumor (AtT-20) by corticosteroid in mice. A transplantable ACTH-secreting pituitary tumor (AtT-20) in mice was studied for its growth in relation to adrenocortical steroid. The latency of transplanted tumor in LAF-1 mice with 10(6) tumor cells was about 2 weeks in adrenalectomized and in intact mice. In the former, however, tumor size reached 1.5 cm in diameter within 1 month, while it remained about 0.5 cm in the latter. Macroscopic and microscopic observation revealed that the tumor grafted in intact mice showed massive necrosis, leaving minimum intact tumor cells among necrotic foci. In contrast, the tumor grafted in adrenalectomized mice was healthy, soft, and showed adenomatous structure. It is concluded that excess of adrenocortical steroid produced in the grafted AtT-20 was inhibitory for the growth of transplanted tumor and removal of the adrenal glands was good for growth and survival of transplanted tumor. For the assessment of direct effect of adrenal steroid on AtT-20 cells, incorporation of 3H-thymidine in cultured AtT-20 cells was examined in a medium supplemented with glucocorticoid hormone. The autoradiographic study indicated that the inhibition of 3H-thymidine uptake was demonstrated at 24 hr after incubation with steroid and labeled cells were barely detectable on 3rd and 5th day."}
{"id": "PMID:213337", "title": "Occurrence of antibody against intracytoplasmic A-particles of mouse mammary tumor virus in sera from breast cancer patients.", "content": "Acetone-fixed smears of DBA/2 mouse leukemia cells that produce clusters of intracytoplasmic A-particles (pronucleocapsids of mouse mammary tumor virus) were employed as an indirect immunofluorescence system to detect the antibody to A-particles in human sera. With positive test sera, specific fluorescence was easily detectable as discrete cytoplasmic granules at the site of A-particle clusters. The antibody was found in 26 (60%) out of 43 breast cancer patient sera and 4 (25%) of 16 mammary fibroadenoma patient sera, while only 4 (11%) out of 37 control woman sera were antibody-positive. In the case of breast cancer patients, occurrence of tha antibody was not specifically related to a particular type of tumor histology. In a considerable number of positive cases, the antibody tended to disappear within various lengths of time after surgical operation of the breast cancer.", "contents": "Occurrence of antibody against intracytoplasmic A-particles of mouse mammary tumor virus in sera from breast cancer patients. Acetone-fixed smears of DBA/2 mouse leukemia cells that produce clusters of intracytoplasmic A-particles (pronucleocapsids of mouse mammary tumor virus) were employed as an indirect immunofluorescence system to detect the antibody to A-particles in human sera. With positive test sera, specific fluorescence was easily detectable as discrete cytoplasmic granules at the site of A-particle clusters. The antibody was found in 26 (60%) out of 43 breast cancer patient sera and 4 (25%) of 16 mammary fibroadenoma patient sera, while only 4 (11%) out of 37 control woman sera were antibody-positive. In the case of breast cancer patients, occurrence of tha antibody was not specifically related to a particular type of tumor histology. In a considerable number of positive cases, the antibody tended to disappear within various lengths of time after surgical operation of the breast cancer."}
{"id": "PMID:213338", "title": "Phosphorylation of 1-beta-D-arabinofuranosylcytosine by the cell-free extract of rat ascites hepatoma, in relation to the mechanism of natural resistance.", "content": "The enzyme that phosphorylates 1-beta-D-arabinofuranosylcytosine (ara-C) was examined in rat ascites hepatomas to clarify whether the capacity for the phosphorylation of ara-C would be related to natural resistance of the tumors to ara-C. Ara-C kinase activity in AH-66F cells, which were moderately sensitive to ara-C, was approximately the same as that in the bone marrow of tumor-bearing rats. L-1210 leukemia, which is sensitive to ara-C, had a higher activity of the enzyme than the mouse bone marrow. On the other hand, the naturally resistant hepatomas, AH-60C, AH-109A, and AH-66, were low in their ara-C kinase activity. The enzyme activity in the cytoplasmic extract (30,000 g supernatant) of the tumor and bone marrow cells was nearly proportional to the capacity for ara-C phosphorylation in intact cells. Thus, the mechanism of natural resistance to ara-C in rat ascites hepatomas was attributed mainly to the low levels of ara-C kinase activity itself. Apparent Km of the enzyme for ara-C was about 170 micron. However, probably due to the presence of the uncompetitive type of inhibitor(s), the level of apparent Km lowered close to 40 micron at higher concentration of the protein as the source of the enzyme, showing similarity to the value in intact cells.", "contents": "Phosphorylation of 1-beta-D-arabinofuranosylcytosine by the cell-free extract of rat ascites hepatoma, in relation to the mechanism of natural resistance. The enzyme that phosphorylates 1-beta-D-arabinofuranosylcytosine (ara-C) was examined in rat ascites hepatomas to clarify whether the capacity for the phosphorylation of ara-C would be related to natural resistance of the tumors to ara-C. Ara-C kinase activity in AH-66F cells, which were moderately sensitive to ara-C, was approximately the same as that in the bone marrow of tumor-bearing rats. L-1210 leukemia, which is sensitive to ara-C, had a higher activity of the enzyme than the mouse bone marrow. On the other hand, the naturally resistant hepatomas, AH-60C, AH-109A, and AH-66, were low in their ara-C kinase activity. The enzyme activity in the cytoplasmic extract (30,000 g supernatant) of the tumor and bone marrow cells was nearly proportional to the capacity for ara-C phosphorylation in intact cells. Thus, the mechanism of natural resistance to ara-C in rat ascites hepatomas was attributed mainly to the low levels of ara-C kinase activity itself. Apparent Km of the enzyme for ara-C was about 170 micron. However, probably due to the presence of the uncompetitive type of inhibitor(s), the level of apparent Km lowered close to 40 micron at higher concentration of the protein as the source of the enzyme, showing similarity to the value in intact cells."}
{"id": "PMID:213340", "title": "Clinicopathological study on 100 early gastric cancer cases.", "content": "Clinicopathological study was given to 100 early gastric cancer cases. The cases included 50 intramucosal lesions (m-group) and 62 submucosal lesions (sm-group), and the share is 17% of whole cases treated surgically. The sex ratio is about 2:1 (male : female). According to the classification by location, the occurrence rate of lesion on anterior wall is 18.8%. This fact suggests the impotance of roentgenscopy by compression technique and double contrast in a prone position focussed on anterior wall. In addition, endoscopy is essential in order to detect minute cancers. The rates of metastasis of early gastric cancers is 2.4% of m-group and 16.1% of sm-group. No metastasis occurs in protruded or elevated type as far as cancer cells remain within the mucosa. Once cancer cells infiltrate into the submucosa, metastasis is observed in 36%. In the present cases, 9 (9%) out of 100 cases of early gastric cancers are the multiple cases. In order to avoid oversight of cancer foci, the portion of stomach to be remained after surgery should be throughly examined prior to operation and again under direct vision after gastric incision.", "contents": "Clinicopathological study on 100 early gastric cancer cases. Clinicopathological study was given to 100 early gastric cancer cases. The cases included 50 intramucosal lesions (m-group) and 62 submucosal lesions (sm-group), and the share is 17% of whole cases treated surgically. The sex ratio is about 2:1 (male : female). According to the classification by location, the occurrence rate of lesion on anterior wall is 18.8%. This fact suggests the impotance of roentgenscopy by compression technique and double contrast in a prone position focussed on anterior wall. In addition, endoscopy is essential in order to detect minute cancers. The rates of metastasis of early gastric cancers is 2.4% of m-group and 16.1% of sm-group. No metastasis occurs in protruded or elevated type as far as cancer cells remain within the mucosa. Once cancer cells infiltrate into the submucosa, metastasis is observed in 36%. In the present cases, 9 (9%) out of 100 cases of early gastric cancers are the multiple cases. In order to avoid oversight of cancer foci, the portion of stomach to be remained after surgery should be throughly examined prior to operation and again under direct vision after gastric incision."}
{"id": "PMID:213341", "title": "Serum alkaline phosphatase (Al-Pase) isozyme in gastric and colonic cancer (using a simple thin layer polyacrylamide gel electrophoresis).", "content": "Using the simple thin layer polyacrylamide gel electrophoresis, serum alkaline phosphatase could be separated 5 isozyme bands in various digestive diseases, consisting of 54 cases of gastric cancer, 11 of colonic cancer, 12 of hepatoma, 4 of cholangioma, 14 of pancreatic cancer, 81 of benign hepatobilliary diseases, 13 of cancers of other organs and 61 of control. The obtained results were as follows: 1) The electrophoretic analysis of serum alkaline phosphatase showed the specific band remaining at the origin, already reported as \"alkaline phosphatase O\", in primary and metastatic cancer of the liver and cholelithiasis. On the contrary, alkaline phosphatase O was never found in gastric and colonic cancer without cholelithiasis. On the contrary, alkaline phosphatase O was never found in gastric and colonic cancer without cancerous metastasis to the liver, and it was also inclined to be positive with the progress of liver metastasis among them. 2) Intestinal alkaline phosphatase was usually found in higher frequency in blood group B and O than in the others, and it was apt to disappear in gastric or colonic cancer with an exacerbation of its cancerous lesions. 3) Heat-stable alkaline phosphatase was found in 10% of gastric or colonic cancer, all of which were histologically proved to be well differentiated adenocarcinoma.", "contents": "Serum alkaline phosphatase (Al-Pase) isozyme in gastric and colonic cancer (using a simple thin layer polyacrylamide gel electrophoresis). Using the simple thin layer polyacrylamide gel electrophoresis, serum alkaline phosphatase could be separated 5 isozyme bands in various digestive diseases, consisting of 54 cases of gastric cancer, 11 of colonic cancer, 12 of hepatoma, 4 of cholangioma, 14 of pancreatic cancer, 81 of benign hepatobilliary diseases, 13 of cancers of other organs and 61 of control. The obtained results were as follows: 1) The electrophoretic analysis of serum alkaline phosphatase showed the specific band remaining at the origin, already reported as \"alkaline phosphatase O\", in primary and metastatic cancer of the liver and cholelithiasis. On the contrary, alkaline phosphatase O was never found in gastric and colonic cancer without cholelithiasis. On the contrary, alkaline phosphatase O was never found in gastric and colonic cancer without cancerous metastasis to the liver, and it was also inclined to be positive with the progress of liver metastasis among them. 2) Intestinal alkaline phosphatase was usually found in higher frequency in blood group B and O than in the others, and it was apt to disappear in gastric or colonic cancer with an exacerbation of its cancerous lesions. 3) Heat-stable alkaline phosphatase was found in 10% of gastric or colonic cancer, all of which were histologically proved to be well differentiated adenocarcinoma."}
{"id": "PMID:213345", "title": "Cyclic AMP metabolism and adenylate cyclase concentration in patients with advanced hepatic cirrhosis.", "content": "Glucagon was tested for its effect on plasma adenosine 3',5'-cyclic monophosphate (cyclic AMP), insulin, and glucose in healthy subjects and in patients with advanced cirrhosis of the liver. In the normal subjects, intravenous infusion of glucagon caused a significant increase in plasma cyclic AMP, glucose, and insulin. In advanced cirrhotics, plasma cyclic AMP, glucose, and insulin did not increase. Adenylate cyclase concentration was measured in liver tissue from end stage cirrhotic patients and from brain-dead organ donors whose cardiovascular function was maintained in a stable state. Basal and total adenylate cyclase concentration were not different in the two groups. Adenylate cyclase from the livers of advanced cirrhotics was, however, significantly less responsive to glucagon stimulation than was that from donor livers. Hepatocytes in advanced cirrhosis have abnormal metabolic behavior characterized by abnormal adenylate cyclase-cyclic AMP response to hormonal stimulation.", "contents": "Cyclic AMP metabolism and adenylate cyclase concentration in patients with advanced hepatic cirrhosis. Glucagon was tested for its effect on plasma adenosine 3',5'-cyclic monophosphate (cyclic AMP), insulin, and glucose in healthy subjects and in patients with advanced cirrhosis of the liver. In the normal subjects, intravenous infusion of glucagon caused a significant increase in plasma cyclic AMP, glucose, and insulin. In advanced cirrhotics, plasma cyclic AMP, glucose, and insulin did not increase. Adenylate cyclase concentration was measured in liver tissue from end stage cirrhotic patients and from brain-dead organ donors whose cardiovascular function was maintained in a stable state. Basal and total adenylate cyclase concentration were not different in the two groups. Adenylate cyclase from the livers of advanced cirrhotics was, however, significantly less responsive to glucagon stimulation than was that from donor livers. Hepatocytes in advanced cirrhosis have abnormal metabolic behavior characterized by abnormal adenylate cyclase-cyclic AMP response to hormonal stimulation."}
{"id": "PMID:213349", "title": "Perhexiline maleate-induced cirrhosis.", "content": "The authors report the cases of 2 patients who died from cirrhosis after receiving perhexiline maleate, a drug widely used in Europe for the treatment of angina pectoris. Perhexiline maleate had been ingested for 24 and 28 mo, respectively. Manifestations of cirrhosis included jaundice, hepatic encephalopathy, ascites, and portal hypertension. Associated manifestations of intolerance to perhexiline maleate included peripheral neuropathy in 1 patient and marked weight loss in both. Histologic lesions resembled those observed in patients with alcoholic liver disease. Ultrastructural lesions included numerous enlarged lysosomes containing myeloid figures. Histochemical stains demonstrated increased phospholipid content of the hepatocytes. These findings are consistent with the view that prolonged administration of perhexiline maleate may induce both histologic lesions resembling those of alcoholic liver disease and ultrastructural and histochemical lesions resembling those of phospholipidosis.", "contents": "Perhexiline maleate-induced cirrhosis. The authors report the cases of 2 patients who died from cirrhosis after receiving perhexiline maleate, a drug widely used in Europe for the treatment of angina pectoris. Perhexiline maleate had been ingested for 24 and 28 mo, respectively. Manifestations of cirrhosis included jaundice, hepatic encephalopathy, ascites, and portal hypertension. Associated manifestations of intolerance to perhexiline maleate included peripheral neuropathy in 1 patient and marked weight loss in both. Histologic lesions resembled those observed in patients with alcoholic liver disease. Ultrastructural lesions included numerous enlarged lysosomes containing myeloid figures. Histochemical stains demonstrated increased phospholipid content of the hepatocytes. These findings are consistent with the view that prolonged administration of perhexiline maleate may induce both histologic lesions resembling those of alcoholic liver disease and ultrastructural and histochemical lesions resembling those of phospholipidosis."}
{"id": "PMID:213353", "title": "Ulnar neuropathies in rheumatoid arthritis.", "content": "A loss of functional motor axons in the median and ulnar nerves occurred in half of thirty-three patients with rheumatoid arthritis. Weakness of small hand muscles may predispose to the development of ulnar deviation of the fingers in patients with joint disease at the radio-ulnar and metacarpophalangeal joints. There is no evidence that spasm of small hand muscles is a significant cause of ulnar deviation of the fingers in rheumatoid arthritis. Ulnar deviation of the fingers in rheumatoid arthritis is not due to selective impairment of the ulnar nerve or the deep palmar branch of the ulnar nerve even though ulnar deviation of the fingers can occur in association with such lesions and in the absence of joint disease.", "contents": "Ulnar neuropathies in rheumatoid arthritis. A loss of functional motor axons in the median and ulnar nerves occurred in half of thirty-three patients with rheumatoid arthritis. Weakness of small hand muscles may predispose to the development of ulnar deviation of the fingers in patients with joint disease at the radio-ulnar and metacarpophalangeal joints. There is no evidence that spasm of small hand muscles is a significant cause of ulnar deviation of the fingers in rheumatoid arthritis. Ulnar deviation of the fingers in rheumatoid arthritis is not due to selective impairment of the ulnar nerve or the deep palmar branch of the ulnar nerve even though ulnar deviation of the fingers can occur in association with such lesions and in the absence of joint disease."}
{"id": "PMID:213354", "title": "Syndactyly and split hand. Supplement.", "content": "In a series of studies of clinical and radiological features of hand anomalies, the author has recently encountered cases which may be explained by reference to the relationship between syndactyly and split hand. These cases suggested how the typical split hand is formed prenatally, and it is concluded that the typical split hand should not be classed as \"Arrest of Development of Parts\" due to embryonal failures.", "contents": "Syndactyly and split hand. Supplement. In a series of studies of clinical and radiological features of hand anomalies, the author has recently encountered cases which may be explained by reference to the relationship between syndactyly and split hand. These cases suggested how the typical split hand is formed prenatally, and it is concluded that the typical split hand should not be classed as \"Arrest of Development of Parts\" due to embryonal failures."}
{"id": "PMID:213358", "title": "[Cervix carcinoma as an immunological model. Part 2. In vitro studies and HLA system typing].", "content": "Carcinoma of the cervix uteri is one of the most important tumors in women. The tumor induces an immunological defense reaction against itself in the tumor host. The round cell infiltrate at the tumor invasion line, which predominantly consists of small lymphocytes is the morphological equivalent of this interrelationship. In the lymph-nodes of the drainage area of the tumor certain patterns of reaction can be differentiated, which may be interpreted as humoral or cellular immune reactions. Cellular immune reactions in lymph-nodes of patients operated according to the method of Wertheim-Meigs were correlated with a better prognosis of the tumor disease. The hypothesis of an involvement of the HSV-type II in the genesis of the cervical carcinoma is supported by the increased incidence of antibodies against the virus. Therewith, relations between the stage of disease and the age of the patient were found as a possible basis for the virus hypothesis and the immune reaction to the tumor associated antigens an altered genetic situation may be presumed. Typing in the HLA-system demonstrates an accumulation of the frequency of the antigen B12 in patients with carcinoma of the cervix. These investigations may lead to a differentiated outlook with regard to the detection of risk groups and therapeutical consequences for cervical cancer.", "contents": "[Cervix carcinoma as an immunological model. Part 2. In vitro studies and HLA system typing]. Carcinoma of the cervix uteri is one of the most important tumors in women. The tumor induces an immunological defense reaction against itself in the tumor host. The round cell infiltrate at the tumor invasion line, which predominantly consists of small lymphocytes is the morphological equivalent of this interrelationship. In the lymph-nodes of the drainage area of the tumor certain patterns of reaction can be differentiated, which may be interpreted as humoral or cellular immune reactions. Cellular immune reactions in lymph-nodes of patients operated according to the method of Wertheim-Meigs were correlated with a better prognosis of the tumor disease. The hypothesis of an involvement of the HSV-type II in the genesis of the cervical carcinoma is supported by the increased incidence of antibodies against the virus. Therewith, relations between the stage of disease and the age of the patient were found as a possible basis for the virus hypothesis and the immune reaction to the tumor associated antigens an altered genetic situation may be presumed. Typing in the HLA-system demonstrates an accumulation of the frequency of the antigen B12 in patients with carcinoma of the cervix. These investigations may lead to a differentiated outlook with regard to the detection of risk groups and therapeutical consequences for cervical cancer."}
{"id": "PMID:213359", "title": "Parathyroid hormone and triglyceride transport: effects on triglyceride secretion rates and adipose tissue lipoprotein lipase in the rat.", "content": "In order to determine the effects of parathyroid hormone on triglyceride transport, male Sprague-Dawley rats were injected with parathyroid extract for eight days and triglyceride secretion rates (TGSR) and adipose tissue lipoprotein lipase (LPL) activity were determined. Parathyroid hormone-treated rats demonstrated significantly lower (p less than .005) TGSR in the basal overnight fasted state 15 hours after the previous injection, but this effect on TGSR was not apparent 3 hours after PTE injection when the rats were allowed to eat. In contrast, LPL activity was significantly reduced in the PTH-treated animals at 3 hours and no effect was apparent on this index of triglyceride removal at 15 hours. These findings suggest that parathyroid hormone may exert independent influences on triglyceride production and removal and thus may alter triglyceride homeostasis in conditions in which parathyroid hormone levels are abnormally increased.", "contents": "Parathyroid hormone and triglyceride transport: effects on triglyceride secretion rates and adipose tissue lipoprotein lipase in the rat. In order to determine the effects of parathyroid hormone on triglyceride transport, male Sprague-Dawley rats were injected with parathyroid extract for eight days and triglyceride secretion rates (TGSR) and adipose tissue lipoprotein lipase (LPL) activity were determined. Parathyroid hormone-treated rats demonstrated significantly lower (p less than .005) TGSR in the basal overnight fasted state 15 hours after the previous injection, but this effect on TGSR was not apparent 3 hours after PTE injection when the rats were allowed to eat. In contrast, LPL activity was significantly reduced in the PTH-treated animals at 3 hours and no effect was apparent on this index of triglyceride removal at 15 hours. These findings suggest that parathyroid hormone may exert independent influences on triglyceride production and removal and thus may alter triglyceride homeostasis in conditions in which parathyroid hormone levels are abnormally increased."}
{"id": "PMID:213363", "title": "Studies on cytochrome c oxidase, II. The chemical constitution of a short polypeptide from the beef heart enzyme.", "content": "A low molecular weight (approximately 6000) polypeptide fraction was isolated from beef heart cytochrome c oxidase, consisting of three peptides with the N-terminal end groups isoleucine, phenylalanine and serine. The complete amino acid sequence of the serine component is described. From the chemical constitution, a site-specific cleavage from a precursor protein and a possible function in membrane penetration and complex formation of the oxidase is inferred.", "contents": "Studies on cytochrome c oxidase, II. The chemical constitution of a short polypeptide from the beef heart enzyme. A low molecular weight (approximately 6000) polypeptide fraction was isolated from beef heart cytochrome c oxidase, consisting of three peptides with the N-terminal end groups isoleucine, phenylalanine and serine. The complete amino acid sequence of the serine component is described. From the chemical constitution, a site-specific cleavage from a precursor protein and a possible function in membrane penetration and complex formation of the oxidase is inferred."}
{"id": "PMID:213366", "title": "Superoxide-independent platelet response to xanthine oxidase.", "content": "Xanthine oxidase (1--5 microgram/ml) from cow's milk induces shape change, aggregation, and the release reaction of human washed platelets. Xanthine oxidase plus xanthine produce superoxide radicals, which reduce nitro blue tetrazolium. Superoxide dismutase, allopurinol, or ommission of xanthine inhibits the reduction of nitro blue tetrazolium but has no influence on the platelet response to xanthine oxidase. In contrast, small amounts of plasma or apyrase from potatoes abolish the effect on platelets, but not the enzyme activity of xanthine oxidase. Comparison of two xanthine oxidase preparations shows that higher specific enzyme activity corresponds to a lesser effect on platelets. The results suggest that platelet and enzyme activities reside in different components of xanthine oxidase preparations.", "contents": "Superoxide-independent platelet response to xanthine oxidase. Xanthine oxidase (1--5 microgram/ml) from cow's milk induces shape change, aggregation, and the release reaction of human washed platelets. Xanthine oxidase plus xanthine produce superoxide radicals, which reduce nitro blue tetrazolium. Superoxide dismutase, allopurinol, or ommission of xanthine inhibits the reduction of nitro blue tetrazolium but has no influence on the platelet response to xanthine oxidase. In contrast, small amounts of plasma or apyrase from potatoes abolish the effect on platelets, but not the enzyme activity of xanthine oxidase. Comparison of two xanthine oxidase preparations shows that higher specific enzyme activity corresponds to a lesser effect on platelets. The results suggest that platelet and enzyme activities reside in different components of xanthine oxidase preparations."}
{"id": "PMID:213368", "title": "A social interaction program for chronic psychiatric patients living in a community residence.", "content": "A psychiatric center in Brooklyn provided a socialization program in a community residence for adults discharged from state hospitals and made a study of the program's outcome. Residents on two floors of the home, the experimental group, received an enriched treatment program; those on the other four floors, the control group, received a minimum of therapeutic intervention. A comparison of residents' ratings on assessment scales made early in the program and after seven months of operation showed that residents on all floors improved on measures of socialization, men improved more than women, and residents over 65 years of age improved the least. Residents in the experimental group did not improve much more than those in the control group. Costs for the experimental group, including room and board, were $16.59 a day per resident. Costs for the control group were $15.61 a day per resident.", "contents": "A social interaction program for chronic psychiatric patients living in a community residence. A psychiatric center in Brooklyn provided a socialization program in a community residence for adults discharged from state hospitals and made a study of the program's outcome. Residents on two floors of the home, the experimental group, received an enriched treatment program; those on the other four floors, the control group, received a minimum of therapeutic intervention. A comparison of residents' ratings on assessment scales made early in the program and after seven months of operation showed that residents on all floors improved on measures of socialization, men improved more than women, and residents over 65 years of age improved the least. Residents in the experimental group did not improve much more than those in the control group. Costs for the experimental group, including room and board, were $16.59 a day per resident. Costs for the control group were $15.61 a day per resident."}
{"id": "PMID:213370", "title": "Leukocytes as secretory organs of inflammation.", "content": "Polymorphonuclear leukocytes secrete substances that defend against foreign invaders by mechanisms that bear remarkable resemblances to those of exocrine and endocrine glands. Similarly, leukocyte secretions can also damage the very host they are intended to protect. Like other secretory cells, leukocytes also bear surface receptors to detect signals that initiate secretion. Clinical implications are detailed.", "contents": "Leukocytes as secretory organs of inflammation. Polymorphonuclear leukocytes secrete substances that defend against foreign invaders by mechanisms that bear remarkable resemblances to those of exocrine and endocrine glands. Similarly, leukocyte secretions can also damage the very host they are intended to protect. Like other secretory cells, leukocytes also bear surface receptors to detect signals that initiate secretion. Clinical implications are detailed."}
{"id": "PMID:213372", "title": "The kidney in health and disease: IV. Principles of ion and water transport in the kidney.", "content": "Modifications within tubular cells facilitate both outward movement and reabsorption of water and solutes through the lipid bilayer plasma membrane. The membrane transport systems that regulate these movements involve processes that obey the laws governing membrane transport in all biologic systems. Evidence that independent pathways for water and for certain ions may exist in cell membranes is discussed.", "contents": "The kidney in health and disease: IV. Principles of ion and water transport in the kidney. Modifications within tubular cells facilitate both outward movement and reabsorption of water and solutes through the lipid bilayer plasma membrane. The membrane transport systems that regulate these movements involve processes that obey the laws governing membrane transport in all biologic systems. Evidence that independent pathways for water and for certain ions may exist in cell membranes is discussed."}
{"id": "PMID:213373", "title": "Ultrastructural and biochemical analysis of \"undifferentiated\" pulmonary carcinomas.", "content": "Seven cases of \"undifferentiated\" pulmonary carcinoma were studied ultrastructurally; five were of the typical oat cell variety and the remaining two consisted of larger cells. In three of the former and both of the latter cases neurosecretory-like granules were demonstrated. Biochemical analysis of tumor tissue extracts revealed 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamine activity in all instances. No hormonal syndrome or metabolic abnormality was detected in any of the patients. The concomitant morphologic demonstration of neurosecretory-like granules and the presence of 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamines in neoplastic tissue would provide further evidence that these tumors may indeed arise from bronchial endocrine cells and could therefore be classified within the group of neuroendocrine carcinomas. Also it seems apparent that these neuroendocrine bronchial carcinomas may include tumors consisting of cells somewhat larger than the typical oat cell. The observation of 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamine activity in two oat cell carcinomas in which neurosecretory granules could not be demonstrated poses an interesting problem whose solution may only derive from further studies.", "contents": "Ultrastructural and biochemical analysis of \"undifferentiated\" pulmonary carcinomas. Seven cases of \"undifferentiated\" pulmonary carcinoma were studied ultrastructurally; five were of the typical oat cell variety and the remaining two consisted of larger cells. In three of the former and both of the latter cases neurosecretory-like granules were demonstrated. Biochemical analysis of tumor tissue extracts revealed 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamine activity in all instances. No hormonal syndrome or metabolic abnormality was detected in any of the patients. The concomitant morphologic demonstration of neurosecretory-like granules and the presence of 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamines in neoplastic tissue would provide further evidence that these tumors may indeed arise from bronchial endocrine cells and could therefore be classified within the group of neuroendocrine carcinomas. Also it seems apparent that these neuroendocrine bronchial carcinomas may include tumors consisting of cells somewhat larger than the typical oat cell. The observation of 5-hydroxy-3-indoleacetic acid, vanilylmandelic acid, and catecholamine activity in two oat cell carcinomas in which neurosecretory granules could not be demonstrated poses an interesting problem whose solution may only derive from further studies."}
{"id": "PMID:213375", "title": "The role of electron microscopy in the diagnosis of unusual peripheral lung tumors.", "content": "The ultrastructure of the lung provides a cytomorphologic basis for the identification of unusual pulmonary neoplasms or unusual histologic variants of more common pulmonary lesions. Comparison of tumor cells with bronchioloalveolar lining cells and with pleural components has aided in the diagnosis of a spindle cell variant of a peripheral neuroendocrine cell tumor (carcinoid) and a tumor composed of cells resembling bronchioloalveolar epithelium (sclerosing hemangioma of lung).", "contents": "The role of electron microscopy in the diagnosis of unusual peripheral lung tumors. The ultrastructure of the lung provides a cytomorphologic basis for the identification of unusual pulmonary neoplasms or unusual histologic variants of more common pulmonary lesions. Comparison of tumor cells with bronchioloalveolar lining cells and with pleural components has aided in the diagnosis of a spindle cell variant of a peripheral neuroendocrine cell tumor (carcinoid) and a tumor composed of cells resembling bronchioloalveolar epithelium (sclerosing hemangioma of lung)."}
{"id": "PMID:213376", "title": "Leukotic spread: an unusual tumor transition.", "content": "This report concerns a case of lung cancer, which is of interest because it proves that an epithelial tumor is capable of spreading in a manner morphologically identical to that of a malignant lymphoreticular tumor.", "contents": "Leukotic spread: an unusual tumor transition. This report concerns a case of lung cancer, which is of interest because it proves that an epithelial tumor is capable of spreading in a manner morphologically identical to that of a malignant lymphoreticular tumor."}
{"id": "PMID:213379", "title": "Lysosomal acid hydrolases in established lymphoblastoid cell lines, transformed by Epstein-Barr virus, from patients with genetic lysosomal storage diseases.", "content": "Lysosomal acid hydrolases were determined in established lymphoblastoid cell lines, transformed in vitro by Epstein-Barr virus (EBV) from lymphocyte-rich cell populations isolated from the peripheral blood of patients with genetic lysosomal storage diseases--Hurler syndrome, Scheie syndrome, GM1-gangliosidosis type 1 and type 2, Tay-Sachs disease, and I-cell disease--and from obligate heterozygotes for these diseases. The respective enzyme activity was undectectable in lymphoblastoid cells from the patients, but not from controls. Obligate heterozygotes could not always be distinguished from controls in lymphoblastoid cells as well as in leukocytes. These results suggest that established lymphoblastoid cell lines are useful material for the enzymatic study of genetic lysosomal storage diseases.", "contents": "Lysosomal acid hydrolases in established lymphoblastoid cell lines, transformed by Epstein-Barr virus, from patients with genetic lysosomal storage diseases. Lysosomal acid hydrolases were determined in established lymphoblastoid cell lines, transformed in vitro by Epstein-Barr virus (EBV) from lymphocyte-rich cell populations isolated from the peripheral blood of patients with genetic lysosomal storage diseases--Hurler syndrome, Scheie syndrome, GM1-gangliosidosis type 1 and type 2, Tay-Sachs disease, and I-cell disease--and from obligate heterozygotes for these diseases. The respective enzyme activity was undectectable in lymphoblastoid cells from the patients, but not from controls. Obligate heterozygotes could not always be distinguished from controls in lymphoblastoid cells as well as in leukocytes. These results suggest that established lymphoblastoid cell lines are useful material for the enzymatic study of genetic lysosomal storage diseases."}
{"id": "PMID:213380", "title": "Superoxide production from human polymorphonuclear leucocytes stimulated with immunoglobulins of different classes and fragments of IgG bound to polystyrene dishes.", "content": "Polystyrene surfaces coated with proteins at alkaline pH were found to be useful to investigate the stimulation of neutrophils independently of phagocytosis. Human neutrophils, when exposed to appropriate stimuli, release superoxide anion (O2-). We have measured superoxide dismutase-inhibitable cytochrome c reduction by cells stimulated with various kinds of protein coated on polystyrene dishes. Native immunoglobulins in solution did not stimulate O2- generation in neutrophils. IgG and IgA adherent to polystyrene dishes stimulated O2- generation in neutrophils, but IgM, IgD, IgE, albumin, Fab, and Fc of IgG on polystyrene dishes did not.", "contents": "Superoxide production from human polymorphonuclear leucocytes stimulated with immunoglobulins of different classes and fragments of IgG bound to polystyrene dishes. Polystyrene surfaces coated with proteins at alkaline pH were found to be useful to investigate the stimulation of neutrophils independently of phagocytosis. Human neutrophils, when exposed to appropriate stimuli, release superoxide anion (O2-). We have measured superoxide dismutase-inhibitable cytochrome c reduction by cells stimulated with various kinds of protein coated on polystyrene dishes. Native immunoglobulins in solution did not stimulate O2- generation in neutrophils. IgG and IgA adherent to polystyrene dishes stimulated O2- generation in neutrophils, but IgM, IgD, IgE, albumin, Fab, and Fc of IgG on polystyrene dishes did not."}
{"id": "PMID:213382", "title": "Persistent shedding of adenovirus in urine of chimpanzees.", "content": "A new adenovirus, designated Pan 11, was isolated repeatedly from the urine of several chimpanzees for more than 1 year. One chimpanzee had chronic interstitial nephritis; the others were healthy. Most chimpanzees tested had neutralizing antibodies to Pan 11 virus in the serum; three people who worked with chimpanzees also acquired antibodies. Transplantable rhabdomyosarcomas developed in hamsters inoculated as newborns with Pan 11 virus.", "contents": "Persistent shedding of adenovirus in urine of chimpanzees. A new adenovirus, designated Pan 11, was isolated repeatedly from the urine of several chimpanzees for more than 1 year. One chimpanzee had chronic interstitial nephritis; the others were healthy. Most chimpanzees tested had neutralizing antibodies to Pan 11 virus in the serum; three people who worked with chimpanzees also acquired antibodies. Transplantable rhabdomyosarcomas developed in hamsters inoculated as newborns with Pan 11 virus."}
{"id": "PMID:213383", "title": "Analysis of antigenic diversity among human cytomegaloviruses by kinetic neutralization tests with high-titered rabbit antisera.", "content": "Neutralizing antisera to human cytomegalovirus were produced in rabbits with alkaline-buffered extracts of infected cell cultures. The antibody activity was complement dependent and associated primarily with the 7S immunoglobulin fraction. Antisera with homologous K values greater than 10.00 were shown to be suitable for neutralization kinetic studies and were so used to examine the antigenic relatedness of strains AD169, Davis, Esp, C-87, Kerr, and Towne. Based upon the degree of relationship as determined by normalized K values, antisera to the Davis or AD169 strains discriminated three antigenic groups, and an antiserum to strain Esp discriminated two groups.", "contents": "Analysis of antigenic diversity among human cytomegaloviruses by kinetic neutralization tests with high-titered rabbit antisera. Neutralizing antisera to human cytomegalovirus were produced in rabbits with alkaline-buffered extracts of infected cell cultures. The antibody activity was complement dependent and associated primarily with the 7S immunoglobulin fraction. Antisera with homologous K values greater than 10.00 were shown to be suitable for neutralization kinetic studies and were so used to examine the antigenic relatedness of strains AD169, Davis, Esp, C-87, Kerr, and Towne. Based upon the degree of relationship as determined by normalized K values, antisera to the Davis or AD169 strains discriminated three antigenic groups, and an antiserum to strain Esp discriminated two groups."}
{"id": "PMID:213384", "title": "Interstitial pneumonia and subclinical infection after intranasal inoculation of murine cytomegalovirus.", "content": "Although cytomegalovirus (CMV) infections are common throughout the world, little is known about the means of person-to-person transmission. To determine whether infection could be established by a respiratory route, studies were conducted in a murine CMV (MCMV) model by using intranasal inoculation. The infectious dose which resulted in pulmonary and systemic infection of half the mice was 100 plaque-forming units of MCMV. Here, infection was subclinical, but virus replicated in the lungs and subsequently disseminated via the blood to other organs within 7 days. The serum immunofluorescence antibody titer peaked by day 21. None of these mice died, although focal peribronchial interstitial pneumonitis was found in infected animals. In mice given greater than or equal to 10(4) plaque-forming units of MCMV intranasally, severe diffuse interstitial pneumonitis resulted uniformly, closely resembling that seen in immunocompromised patients and in newborn infants, and 20% of the animals died. Normal pulmonary architecture was obliterated by sheets of histiocytes, many containing MCMV intranuclear inclusions, and by accumulation of proteinaceous fluid in the interstitial and alveolar spaces. Of relevance to human disease, these experiments show that MCMV as a sole pathogen can cause severe interstitial pneumonitis in normal mice and that subclinical systemic infection results from respiratory inoculation of small amounts of virus.", "contents": "Interstitial pneumonia and subclinical infection after intranasal inoculation of murine cytomegalovirus. Although cytomegalovirus (CMV) infections are common throughout the world, little is known about the means of person-to-person transmission. To determine whether infection could be established by a respiratory route, studies were conducted in a murine CMV (MCMV) model by using intranasal inoculation. The infectious dose which resulted in pulmonary and systemic infection of half the mice was 100 plaque-forming units of MCMV. Here, infection was subclinical, but virus replicated in the lungs and subsequently disseminated via the blood to other organs within 7 days. The serum immunofluorescence antibody titer peaked by day 21. None of these mice died, although focal peribronchial interstitial pneumonitis was found in infected animals. In mice given greater than or equal to 10(4) plaque-forming units of MCMV intranasally, severe diffuse interstitial pneumonitis resulted uniformly, closely resembling that seen in immunocompromised patients and in newborn infants, and 20% of the animals died. Normal pulmonary architecture was obliterated by sheets of histiocytes, many containing MCMV intranuclear inclusions, and by accumulation of proteinaceous fluid in the interstitial and alveolar spaces. Of relevance to human disease, these experiments show that MCMV as a sole pathogen can cause severe interstitial pneumonitis in normal mice and that subclinical systemic infection results from respiratory inoculation of small amounts of virus."}
{"id": "PMID:213385", "title": "Ultracentrifugal inoculation of herpes simplex virus.", "content": "By ultracentrifugation of 30 ml of highly dilute suspensions of herpes simplex virus (HSV) directly onto monolayer cultures grown in centrifuge tubes, infectivity was significantly greater than without centrifugation. Ultracentrifugation at 20,000 to 25,000 rpm (28,000 to 45,000 X g) for 1.5 to 2.3 h was utilized with good preservation of cultures. With low-speed centrifugation at 3,000 rpm (1,100 X g), infectivity was almost 10-fold greater than without centrifugation. With ultracentrifugal inoculation, infectivity was about 100-fold greater than without centrifugation. Ultracentrifugal inoculation permitted the detection of HSV at concentrations as low as 0.05 plaque-forming units per ml. Similarly, ultracentrifugal inoculation of cultures was almost 100-fold more sensitive a method of detecting infectious HSV than was pelleting HSV from dilute suspensions followed by resuspension and inoculation of cultures. Ultracentrifugal inoculation of cultures may permit the isolation of HSV in situations where virus cannot be detected by ordinary means and may prove applicable to the study of other viruses.", "contents": "Ultracentrifugal inoculation of herpes simplex virus. By ultracentrifugation of 30 ml of highly dilute suspensions of herpes simplex virus (HSV) directly onto monolayer cultures grown in centrifuge tubes, infectivity was significantly greater than without centrifugation. Ultracentrifugation at 20,000 to 25,000 rpm (28,000 to 45,000 X g) for 1.5 to 2.3 h was utilized with good preservation of cultures. With low-speed centrifugation at 3,000 rpm (1,100 X g), infectivity was almost 10-fold greater than without centrifugation. With ultracentrifugal inoculation, infectivity was about 100-fold greater than without centrifugation. Ultracentrifugal inoculation permitted the detection of HSV at concentrations as low as 0.05 plaque-forming units per ml. Similarly, ultracentrifugal inoculation of cultures was almost 100-fold more sensitive a method of detecting infectious HSV than was pelleting HSV from dilute suspensions followed by resuspension and inoculation of cultures. Ultracentrifugal inoculation of cultures may permit the isolation of HSV in situations where virus cannot be detected by ordinary means and may prove applicable to the study of other viruses."}
{"id": "PMID:213386", "title": "Lymphocyte-mediated cytotoxicity in humans during revaccination with vaccinia virus.", "content": "Fifteen healthy human volunteers were revaccinated with vaccinia virus. Blood samples (4 to 7) were obtained during the 3 weeks after revaccination. Peripheral blood lymphocytes were washed extensively and tested for cytotoxicity against vaccinia-infected autologous and/or homologous skin fibroblasts. Without addition of antibodies, peak levels of killing were observed on days 7 to 9. The killing did not depend on common HLA markers. On days with peak activity, extensively washed lymphocytes showed higher levels of killing than normally washed lymphocytes. By cell separation experiments, the cell most active in killing proved to be a nonadherent, non-phagocytizing lymphocyte with Fc receptors. Serum antibodies tested in two sensitive serological assays peaked on days 14 to 17. The question of whether the killing observed is dependent on or independent of antibodies is not clarified in the present study.", "contents": "Lymphocyte-mediated cytotoxicity in humans during revaccination with vaccinia virus. Fifteen healthy human volunteers were revaccinated with vaccinia virus. Blood samples (4 to 7) were obtained during the 3 weeks after revaccination. Peripheral blood lymphocytes were washed extensively and tested for cytotoxicity against vaccinia-infected autologous and/or homologous skin fibroblasts. Without addition of antibodies, peak levels of killing were observed on days 7 to 9. The killing did not depend on common HLA markers. On days with peak activity, extensively washed lymphocytes showed higher levels of killing than normally washed lymphocytes. By cell separation experiments, the cell most active in killing proved to be a nonadherent, non-phagocytizing lymphocyte with Fc receptors. Serum antibodies tested in two sensitive serological assays peaked on days 14 to 17. The question of whether the killing observed is dependent on or independent of antibodies is not clarified in the present study."}
{"id": "PMID:213387", "title": "Effects of ambient temperatures on induction of transmissible gastroenteritis in feeder pigs.", "content": "Experiments were carried out to investigate the effects of ambient temperatures on the induction of transmissible gastroenteritis in feeder pigs 2 to 3 months old. Pigs maintained at a high temperature (30 +/- 2 degrees C) and exposed to the virulent transmissible gastroenteritis virus did not show clinical signs of the disease during their maintenance at the high temperature. On the other hand, a sudden decrease in the ambient temperature, either before or after virus inoculation, induced severe disease in feeder pigs exposed to the virus. However, continuous maintenance of pigs at the low temperature (4 +/- 1 degrees C) tended to somewhat reduce the frequency of occurrence of signs in proportion to the length of the maintenance periods at that temperature. Pigs raised at temperatures that fluctuated between 20 +/- 2 and 4 +/- 1 degrees C every 24 h developed profuse diarrhea. The duration of clinical signs was longer in pigs maintained under the fluctuating temperatures than in those at the constantly low temperature. With one exception, antibody against transmissible gastroenteritis virus was demonstrated in sera collected from pigs both with and without clinical signs. Antibody titers obtained, however, were somewhat higher in sera collected from pigs that had developed clinical signs than in those from pigs that had endured the infection without showing signs.", "contents": "Effects of ambient temperatures on induction of transmissible gastroenteritis in feeder pigs. Experiments were carried out to investigate the effects of ambient temperatures on the induction of transmissible gastroenteritis in feeder pigs 2 to 3 months old. Pigs maintained at a high temperature (30 +/- 2 degrees C) and exposed to the virulent transmissible gastroenteritis virus did not show clinical signs of the disease during their maintenance at the high temperature. On the other hand, a sudden decrease in the ambient temperature, either before or after virus inoculation, induced severe disease in feeder pigs exposed to the virus. However, continuous maintenance of pigs at the low temperature (4 +/- 1 degrees C) tended to somewhat reduce the frequency of occurrence of signs in proportion to the length of the maintenance periods at that temperature. Pigs raised at temperatures that fluctuated between 20 +/- 2 and 4 +/- 1 degrees C every 24 h developed profuse diarrhea. The duration of clinical signs was longer in pigs maintained under the fluctuating temperatures than in those at the constantly low temperature. With one exception, antibody against transmissible gastroenteritis virus was demonstrated in sera collected from pigs both with and without clinical signs. Antibody titers obtained, however, were somewhat higher in sera collected from pigs that had developed clinical signs than in those from pigs that had endured the infection without showing signs."}
{"id": "PMID:213388", "title": "Role of hydrogen peroxide and peroxidase in the cytotoxicity of Trypanosoma dionisii by human granulocytes.", "content": "The mechanism of the cytotoxic reaction of leukocytes to Trypanosoma dionisii was investigated. Cytotoxicity was measured by release of [99mTc]pertechnetate from labeled protozoa. Both granulocytes and lymphocytes were found to be cytotoxic to antibody-coated T. dionisii. The reaction was inhibited by diethyldithiocarbamate and by potassium cyanide, both of which inhibit myeloperoxidase. Myeloperoxidase from azurophil granules was toxic to T. dionisii, provided that hydrogen peroxide was also present. Hydrogen peroxide formation was induced in granulocytes and, to a lesser extent, in lymphocytes by antibody-coated T. dionisii. Inhibition of this hydrogen peroxide formation by treatment of the effector cell surface with p-diazobenzenesulfonic acid inhibited cytotoxicity. It is therefore concluded that granulocytes, and probably also lymphocytes, kill T. dionisii with hydrogen peroxide by a peroxidase-mediated reaction. Although hydrogen peroxide and myeloperoxidase alone were also cytotoxic to the lymphoblastoid cell line CLA4, it seems unlikely that this is the cytotoxic mechanism for this process because these cells were unable to induce hydrogen peroxide formation.", "contents": "Role of hydrogen peroxide and peroxidase in the cytotoxicity of Trypanosoma dionisii by human granulocytes. The mechanism of the cytotoxic reaction of leukocytes to Trypanosoma dionisii was investigated. Cytotoxicity was measured by release of [99mTc]pertechnetate from labeled protozoa. Both granulocytes and lymphocytes were found to be cytotoxic to antibody-coated T. dionisii. The reaction was inhibited by diethyldithiocarbamate and by potassium cyanide, both of which inhibit myeloperoxidase. Myeloperoxidase from azurophil granules was toxic to T. dionisii, provided that hydrogen peroxide was also present. Hydrogen peroxide formation was induced in granulocytes and, to a lesser extent, in lymphocytes by antibody-coated T. dionisii. Inhibition of this hydrogen peroxide formation by treatment of the effector cell surface with p-diazobenzenesulfonic acid inhibited cytotoxicity. It is therefore concluded that granulocytes, and probably also lymphocytes, kill T. dionisii with hydrogen peroxide by a peroxidase-mediated reaction. Although hydrogen peroxide and myeloperoxidase alone were also cytotoxic to the lymphoblastoid cell line CLA4, it seems unlikely that this is the cytotoxic mechanism for this process because these cells were unable to induce hydrogen peroxide formation."}
{"id": "PMID:213389", "title": "Protective effect of early serum from mice after cytomegalovirus infection.", "content": "Serum obtained from mice 3 to 5 days after cytomegalovirus infection contained complement-requiring neutralizing antibody, which, when passively transferred, protected mice from lethal infection with the homologous virus. The active substance was largely heat-stable 7s immunoglobulin.", "contents": "Protective effect of early serum from mice after cytomegalovirus infection. Serum obtained from mice 3 to 5 days after cytomegalovirus infection contained complement-requiring neutralizing antibody, which, when passively transferred, protected mice from lethal infection with the homologous virus. The active substance was largely heat-stable 7s immunoglobulin."}
{"id": "PMID:213390", "title": "Glycoproteins of natural origin with an affinity for hepatitis B surface antigen.", "content": "Sera from certain animal species contain a substance(s) which binds hepatitis B surface antigen. The hepatitis B binding substance found in animals is not antibody, but appears to be a glycoprotein which reacted with antigen-coated beads and produced a \"false positive\" test for antibody. This glycoprotein could be selectively and quantitatively removed by reaction with purified hepatitis B surface antigen and centrifugation. Pili fractions isolated from Neisseria gonorrhoeae and Escherichia coli bound to hepatitis B surface antigen and produced false positive anti-hepatitis B surface antigen reactions. Mouse anti-bovine hepatitis B binding substance and rabbit anti-E. coli pili were capable of neutralizing bovine hepatitis B binding substance.", "contents": "Glycoproteins of natural origin with an affinity for hepatitis B surface antigen. Sera from certain animal species contain a substance(s) which binds hepatitis B surface antigen. The hepatitis B binding substance found in animals is not antibody, but appears to be a glycoprotein which reacted with antigen-coated beads and produced a \"false positive\" test for antibody. This glycoprotein could be selectively and quantitatively removed by reaction with purified hepatitis B surface antigen and centrifugation. Pili fractions isolated from Neisseria gonorrhoeae and Escherichia coli bound to hepatitis B surface antigen and produced false positive anti-hepatitis B surface antigen reactions. Mouse anti-bovine hepatitis B binding substance and rabbit anti-E. coli pili were capable of neutralizing bovine hepatitis B binding substance."}
{"id": "PMID:213391", "title": "Peritoneal macrophage activation indicated by enhanced chemiluminescence.", "content": "A number of studies have demonstrated the ability of various bacterial preparations, protozoa, and chemicals to activate macrophages and concomitantly to enhance host resistance to both tumors and infections. Recently, viral infections have been shown to have a similar effect upon macrophage function. To better define the metabolic state of activated macrophages, we have evaluated the ability of peritoneal cells (PC) from vaccinia virus- or murine cytomegalovirus-infected or Corynebacterium parvum-treated mice to emit chemiluminescence (CL) during phagocytosis of zymosan particles or yeasts. PC from C. parvum-treated mice (1,400 microgram intraperitoneally) emitted enhanced CL over controls on days 3, 6, 14, and 21 after treatment, thereby establishing the emission of CL as a correlate of metabolic activation. Previous evidence for activation of PC from vaccinia virus-infected mice (10(8) plaque-forming units) was confirmed by demonstration of enhanced levels of CL on days 3, 6, and 13 after murine infection. Likewise, PC from mice infected with murine cytomegalovirus (10(5) plaque-forming units) 3, 6, or 13 days previously demonstrated augmented levels of CL over controls. Opsonized virus particles (vaccinia virus or murine cytomegalovirus) failed to induce the emission of CL with PC from mice infected with the isologous virus. Our data further demonstrate the immunomodulationinduced by virus infections and suggest that the detection of CL is an easily quantitated correlate of macrophage activation which may be helpful in defining metabolic alterations induced during activation.", "contents": "Peritoneal macrophage activation indicated by enhanced chemiluminescence. A number of studies have demonstrated the ability of various bacterial preparations, protozoa, and chemicals to activate macrophages and concomitantly to enhance host resistance to both tumors and infections. Recently, viral infections have been shown to have a similar effect upon macrophage function. To better define the metabolic state of activated macrophages, we have evaluated the ability of peritoneal cells (PC) from vaccinia virus- or murine cytomegalovirus-infected or Corynebacterium parvum-treated mice to emit chemiluminescence (CL) during phagocytosis of zymosan particles or yeasts. PC from C. parvum-treated mice (1,400 microgram intraperitoneally) emitted enhanced CL over controls on days 3, 6, 14, and 21 after treatment, thereby establishing the emission of CL as a correlate of metabolic activation. Previous evidence for activation of PC from vaccinia virus-infected mice (10(8) plaque-forming units) was confirmed by demonstration of enhanced levels of CL on days 3, 6, and 13 after murine infection. Likewise, PC from mice infected with murine cytomegalovirus (10(5) plaque-forming units) 3, 6, or 13 days previously demonstrated augmented levels of CL over controls. Opsonized virus particles (vaccinia virus or murine cytomegalovirus) failed to induce the emission of CL with PC from mice infected with the isologous virus. Our data further demonstrate the immunomodulationinduced by virus infections and suggest that the detection of CL is an easily quantitated correlate of macrophage activation which may be helpful in defining metabolic alterations induced during activation."}
{"id": "PMID:213392", "title": "Interferon treatment of NZB mice: accelerated progression of autoimmune disease.", "content": "The effect of long-term administration of interferon in New Zealand Black and New Zealand Black/New Zealand White F1 hybrid mice was studied. Treatment with moderate doses of interferon (10(4) units, five times weekly for 8 weeks) did not depress murine leukemia virus gp69/71 levels in serum and spleen, nor p30 levels in the spleen. Interferon given at 10(5.1) units (three times weekly for 37 weeks) caused an increased incidence of anti-erythrocyte antibodies in New Zealand Black mice. Finally, the hybrid mice given interferon at 10(6.0) units (three times weekly for 33 weeks) had increased renal immune complex deposits and increased incidences of proteinuria and anemia.", "contents": "Interferon treatment of NZB mice: accelerated progression of autoimmune disease. The effect of long-term administration of interferon in New Zealand Black and New Zealand Black/New Zealand White F1 hybrid mice was studied. Treatment with moderate doses of interferon (10(4) units, five times weekly for 8 weeks) did not depress murine leukemia virus gp69/71 levels in serum and spleen, nor p30 levels in the spleen. Interferon given at 10(5.1) units (three times weekly for 37 weeks) caused an increased incidence of anti-erythrocyte antibodies in New Zealand Black mice. Finally, the hybrid mice given interferon at 10(6.0) units (three times weekly for 33 weeks) had increased renal immune complex deposits and increased incidences of proteinuria and anemia."}
{"id": "PMID:213394", "title": "Some aspects of the physiological and pharmacological control of the synthesis of triacylglycerols and phospholipids.", "content": "The effects of dietary modification, starvation, stress and diabetes on the activity of phosphatidate phosphohydrolase are discussed. Evidence is presented that this enzyme is involved in controlling the rate of triacylglycerol synthesis in the liver. Drugs such as fenfluramine and benfluorex are able to inhibit phosphatidate phosphohydrolase by interacting with the substrate. This decreases the rate of triacylglycerol synthesis and redirects the route of glycerolipid metabolism. Benfluroex also partly prevents the ethanol-induced increase in triacylglycerol synthesis and in phosphohydrolase activity. The implications of these findings are discussed with respect to the mode of action of fenfluramine and benfluorex and to the control of triacylglycerol synthesis.", "contents": "Some aspects of the physiological and pharmacological control of the synthesis of triacylglycerols and phospholipids. The effects of dietary modification, starvation, stress and diabetes on the activity of phosphatidate phosphohydrolase are discussed. Evidence is presented that this enzyme is involved in controlling the rate of triacylglycerol synthesis in the liver. Drugs such as fenfluramine and benfluorex are able to inhibit phosphatidate phosphohydrolase by interacting with the substrate. This decreases the rate of triacylglycerol synthesis and redirects the route of glycerolipid metabolism. Benfluroex also partly prevents the ethanol-induced increase in triacylglycerol synthesis and in phosphohydrolase activity. The implications of these findings are discussed with respect to the mode of action of fenfluramine and benfluorex and to the control of triacylglycerol synthesis."}
{"id": "PMID:213395", "title": "The synthesis of N-benzyloxycarbonl-L-prolyl-dehydrophenylalanyl-L-histidyl-L-leucine: a converting-enzyme inhibitor.", "content": "The direct oxidation of a dipeptide azlactone (1) by DDG affords an optically active unsaturated dipeptide azlactone (2). It was shown that the double bond had the Z-configuration and that no racemization of the proline moiety occurred during the oxidation. The dehydrotripeptide, Z-Pro-delta-Phe-Phe OH (9b) was prepared by direct coupling of azlactone (2) with phenylalanine tetramethyl-guanidinium salt and was shown to be stable to chymotrypsin. The tetrapeptide, Z-Pro-delta-Phe-His-Leu  OH (11), was prepared directly from the azlactone (2) and by saponification of the tetrapeptide ester (10) prepared by mixed anhydride coupling of Z-Pro-deltaPhe  OH (7) with the dipeptide ester. The dehydropeptide (11) inhibits angiotensin I converting enzyme (IC50, 1X10-4 M).", "contents": "The synthesis of N-benzyloxycarbonl-L-prolyl-dehydrophenylalanyl-L-histidyl-L-leucine: a converting-enzyme inhibitor. The direct oxidation of a dipeptide azlactone (1) by DDG affords an optically active unsaturated dipeptide azlactone (2). It was shown that the double bond had the Z-configuration and that no racemization of the proline moiety occurred during the oxidation. The dehydrotripeptide, Z-Pro-delta-Phe-Phe OH (9b) was prepared by direct coupling of azlactone (2) with phenylalanine tetramethyl-guanidinium salt and was shown to be stable to chymotrypsin. The tetrapeptide, Z-Pro-delta-Phe-His-Leu  OH (11), was prepared directly from the azlactone (2) and by saponification of the tetrapeptide ester (10) prepared by mixed anhydride coupling of Z-Pro-deltaPhe  OH (7) with the dipeptide ester. The dehydropeptide (11) inhibits angiotensin I converting enzyme (IC50, 1X10-4 M)."}
{"id": "PMID:213398", "title": "The effect of cesium salts on dense poliovirus particles.", "content": "The buoyant density of dense poliovirus particles has been examined in density gradients other than cesium chloride in order to determine the dependence of this property on the nature of the solvent. In Urografin (sodium and methylglucamine amidotrizoate), dense poliovirus particles banded at two densities--1.33 and 1.39 g/cm(3)--whereas in cesium metrizoate they banded only at 1.39 g/cm(3) and in cesium sulfate at 1.38 g/cm(3). The presence of cesium ions gives rise to the occurrence of dense particles, which are indistinguishable in their buoyant density and sedimentation coefficient from standard poliovirus particles when prepared in the absence of Cs+. In their physical properties dense poliovirus particles are more closely related to rhinoviruses and foot-and-mouth-disease virus, i.e., to members of the genus Rhinovirus, than to standard poliovirus particles belonging to the genus Enterovirus.", "contents": "The effect of cesium salts on dense poliovirus particles. The buoyant density of dense poliovirus particles has been examined in density gradients other than cesium chloride in order to determine the dependence of this property on the nature of the solvent. In Urografin (sodium and methylglucamine amidotrizoate), dense poliovirus particles banded at two densities--1.33 and 1.39 g/cm(3)--whereas in cesium metrizoate they banded only at 1.39 g/cm(3) and in cesium sulfate at 1.38 g/cm(3). The presence of cesium ions gives rise to the occurrence of dense particles, which are indistinguishable in their buoyant density and sedimentation coefficient from standard poliovirus particles when prepared in the absence of Cs+. In their physical properties dense poliovirus particles are more closely related to rhinoviruses and foot-and-mouth-disease virus, i.e., to members of the genus Rhinovirus, than to standard poliovirus particles belonging to the genus Enterovirus."}
{"id": "PMID:213399", "title": "Insulin inhibits cellular and herpes simplex virus DNA synthesis in transformed lymphoblastoid cell lines.", "content": "Treatment of uninfected and herpes simplex virus-infected lymphoblastoid cells with 4 units of insulin per milliliter resulted in the inhibition of both cellular and viral DNA synthesis.", "contents": "Insulin inhibits cellular and herpes simplex virus DNA synthesis in transformed lymphoblastoid cell lines. Treatment of uninfected and herpes simplex virus-infected lymphoblastoid cells with 4 units of insulin per milliliter resulted in the inhibition of both cellular and viral DNA synthesis."}
{"id": "PMID:213403", "title": "[Liver resection in benign and malignant tumors].", "content": "Benign tumors of the liver, circumscribed hepatomas and solitary hepatic metastases from colonic cancer are treated by partial liver resection. In case of colonic cancer the hepatic metastasis is resected in a second operation. 20 cases of hepatic resections are reported. 10 right hepatic lobectomies, 1 left hepatic lobectomy and 9 minor resections were performed. Of the 11 patients treated by hepatic lobectomy, one (or 9%) died in the postoperative period (within 30 days after operation). Of the other 9 patients undergoing minor resections there was no death.", "contents": "[Liver resection in benign and malignant tumors]. Benign tumors of the liver, circumscribed hepatomas and solitary hepatic metastases from colonic cancer are treated by partial liver resection. In case of colonic cancer the hepatic metastasis is resected in a second operation. 20 cases of hepatic resections are reported. 10 right hepatic lobectomies, 1 left hepatic lobectomy and 9 minor resections were performed. Of the 11 patients treated by hepatic lobectomy, one (or 9%) died in the postoperative period (within 30 days after operation). Of the other 9 patients undergoing minor resections there was no death."}
{"id": "PMID:213405", "title": "Exhaustive physical exercise and acid hydrolase activity in mouse skeletal muscle. A histochemical study.", "content": "Adult, untrained NMRI mice were exhausted on a motor-driven treadmill by an intermittent-type running programme. Serial cryostate sections for the staining of NADH-tetrazolium reductase, beta-glucuronidase, beta-N-acetylglucosaminidase, and beta-glycerophosphatase activities and for making hematoxylin-eosin staining were cut from m. quadriceps femoris 1, 2, 3, 5, 7, and 15 days after physical exhaustion. A strong increase in the activities of beta-glucuronidase and beta-N-acetylglucosaminidase was observed 7 days after exhaustion and the activity changes, which were similar for the both glycosidases, were more prominent in the highly oxidative red compared to less oxidative white fibres. Activity granules were more numerous in the perinuclear than the interfibrillar area of red fibres. Spots were arranged like longitudinal chains between myofibrils. Activity in connective tissue was usually observed only in animals exhausted 3--7 days earlier. Simultaneous activity in fibres exceeded that in connective tissue. beta-Glycerophosphatase activity was not, by the method used, seen in histologically \"healthy\" or normal-looking fibres. In samples taken 2--5 days after exhaustion some degenerating and necrotic fibres were observed. Inflammatory reaction was also observed being at its strongest five days after loading when mononuclear cells were seen inside necrotic fibres. The number of regenerating muscle cells was most abundant 7 days after exhaustion. It is suggested that temporary hypoxia, which accompanies exhaustive physical exercise in skeletal muscle, upsets the energy metabolism and homeostasis of fibres and causes the observed histological and histochemical alterations, which possess features typical of both lethal and sublethal acute cell injury.", "contents": "Exhaustive physical exercise and acid hydrolase activity in mouse skeletal muscle. A histochemical study. Adult, untrained NMRI mice were exhausted on a motor-driven treadmill by an intermittent-type running programme. Serial cryostate sections for the staining of NADH-tetrazolium reductase, beta-glucuronidase, beta-N-acetylglucosaminidase, and beta-glycerophosphatase activities and for making hematoxylin-eosin staining were cut from m. quadriceps femoris 1, 2, 3, 5, 7, and 15 days after physical exhaustion. A strong increase in the activities of beta-glucuronidase and beta-N-acetylglucosaminidase was observed 7 days after exhaustion and the activity changes, which were similar for the both glycosidases, were more prominent in the highly oxidative red compared to less oxidative white fibres. Activity granules were more numerous in the perinuclear than the interfibrillar area of red fibres. Spots were arranged like longitudinal chains between myofibrils. Activity in connective tissue was usually observed only in animals exhausted 3--7 days earlier. Simultaneous activity in fibres exceeded that in connective tissue. beta-Glycerophosphatase activity was not, by the method used, seen in histologically \"healthy\" or normal-looking fibres. In samples taken 2--5 days after exhaustion some degenerating and necrotic fibres were observed. Inflammatory reaction was also observed being at its strongest five days after loading when mononuclear cells were seen inside necrotic fibres. The number of regenerating muscle cells was most abundant 7 days after exhaustion. It is suggested that temporary hypoxia, which accompanies exhaustive physical exercise in skeletal muscle, upsets the energy metabolism and homeostasis of fibres and causes the observed histological and histochemical alterations, which possess features typical of both lethal and sublethal acute cell injury."}
{"id": "PMID:213412", "title": "Lung tissue guanosine 3',5'-monophosphate: effects of ventilation and anesthesia.", "content": "In vivo levels of guanosine 3',5'-cyclic monophosphate (cGMP) in rat lung were measured by radioimmunoassay. The basal levels of this agent were found to change depending on the method of killing or anesthesia used. Lowest values were found after microwave irradiation to the head (10.2 fmol/mg wet wt). Values after pentobarbitol anesthesia, with or without atropine, were significantly higher (19-24 fmol/mg). In animals anesthetized with pentobarbital and ventilated at pressures of 7 cmH2O with no end-expiratory pressure, lung cGMP was 42-49 fmol/mg. Ventilation at higher pressures resulted in much higher levels of cGMP (20 cmH2O, 105 fmol/mg; 30 cmH2O, 233 fmol/mg). The response of cGMP to ventilation was not blocked by pretreatment of the animals with atropine. High-pressure ventilation was without effect on lung adenosine 3',5'-cyclic monophosphate.", "contents": "Lung tissue guanosine 3',5'-monophosphate: effects of ventilation and anesthesia. In vivo levels of guanosine 3',5'-cyclic monophosphate (cGMP) in rat lung were measured by radioimmunoassay. The basal levels of this agent were found to change depending on the method of killing or anesthesia used. Lowest values were found after microwave irradiation to the head (10.2 fmol/mg wet wt). Values after pentobarbitol anesthesia, with or without atropine, were significantly higher (19-24 fmol/mg). In animals anesthetized with pentobarbital and ventilated at pressures of 7 cmH2O with no end-expiratory pressure, lung cGMP was 42-49 fmol/mg. Ventilation at higher pressures resulted in much higher levels of cGMP (20 cmH2O, 105 fmol/mg; 30 cmH2O, 233 fmol/mg). The response of cGMP to ventilation was not blocked by pretreatment of the animals with atropine. High-pressure ventilation was without effect on lung adenosine 3',5'-cyclic monophosphate."}
{"id": "PMID:213414", "title": "Structural investigation of the antibiotic ristomycin A. 13C-NMR spectral analysis of the interglycosidic linkages of the heterotetrasaccharide side-chain.", "content": "By 13C-NMR studies on Ia, IIa, IIb and IVa obtained by the chemical degradation of ristomycin A and on several synthetic model compounds it has been proved that an O-beta-D-arabinopyranosyl-(1 leads to 2)-O-alpha-D-mannopyranosyl-(1 leads to 2)-O-[alpha-L-rhamnopyranosyl-(1 leads to 6)]-D-glucopyranosyl heterotetrasaccharide moiety is connected to the aglycone of the antibiotic.", "contents": "Structural investigation of the antibiotic ristomycin A. 13C-NMR spectral analysis of the interglycosidic linkages of the heterotetrasaccharide side-chain. By 13C-NMR studies on Ia, IIa, IIb and IVa obtained by the chemical degradation of ristomycin A and on several synthetic model compounds it has been proved that an O-beta-D-arabinopyranosyl-(1 leads to 2)-O-alpha-D-mannopyranosyl-(1 leads to 2)-O-[alpha-L-rhamnopyranosyl-(1 leads to 6)]-D-glucopyranosyl heterotetrasaccharide moiety is connected to the aglycone of the antibiotic."}
{"id": "PMID:213415", "title": "Effects of polymyxin antibiotics on iodohippurate accumulation in rabbit renal cortical slices.", "content": "The in vitro effects of polymyxin antibiotics on 0-125I-hippurate (OIH) accumulation in rabbit renal cortical slices were studied using incubation media with pH ranging from 6.9 to 7.9 and containing polymyxin B sulfate, colistin sulfate, sodium colistimethate and antibacterially inactive N-succinyl colistin in concentrations ranging from 1 to 2,000 microgram base/ml. Polymyxin B, colistin and colistimethate depressed OIH accumulation significantly in concentrations greater than or equal to 300 microgram/ml. The effects on accumulation were clearly pH-dependent and most pronounced at alkaline pH. N-Succinyl colistin had only a marginal influence on accumulation, even in high concentrations. Colistimethate produced a significantly smaller decrease in accumulation at all pH values than both polymyxin B and colistin. The results suggest that the presence of free amino groups is necessary to obtain a decrease in accumulation and correlate with the known in vivo nephrotoxicity of these antibiotics.", "contents": "Effects of polymyxin antibiotics on iodohippurate accumulation in rabbit renal cortical slices. The in vitro effects of polymyxin antibiotics on 0-125I-hippurate (OIH) accumulation in rabbit renal cortical slices were studied using incubation media with pH ranging from 6.9 to 7.9 and containing polymyxin B sulfate, colistin sulfate, sodium colistimethate and antibacterially inactive N-succinyl colistin in concentrations ranging from 1 to 2,000 microgram base/ml. Polymyxin B, colistin and colistimethate depressed OIH accumulation significantly in concentrations greater than or equal to 300 microgram/ml. The effects on accumulation were clearly pH-dependent and most pronounced at alkaline pH. N-Succinyl colistin had only a marginal influence on accumulation, even in high concentrations. Colistimethate produced a significantly smaller decrease in accumulation at all pH values than both polymyxin B and colistin. The results suggest that the presence of free amino groups is necessary to obtain a decrease in accumulation and correlate with the known in vivo nephrotoxicity of these antibiotics."}
{"id": "PMID:213417", "title": "Role of small molecules in regulation of D-serine deaminase synthesis.", "content": "Cyclic AMP is required for optimal synthesis of D-serine deaminase synthesis from dsdO+ templates and for optimal hyperinducible synthesis from low constitutive dsdO templates both in vitro and in vivo. Neither D-serine, cyclic AMP, nor dsdC activator has an effect on expression of a high constitutive dsdO template. The synthesis of the dsdC activator itself in vitro is independent of cyclic AMP. Guanosine tetraphosphate does not have a significant effect on in vitro D-serine deaminase synthesis from dsdO+ or dsdO templates. A previously described class of dsdO mutants showing partial catabolite sensitivity of constitutive D-serine deaminase synthesis proved to be low dsdO types. They all contain a low constitutive dsdC mutation; the two effects are additive with regard to level of constitutivity, but only that portion of synthesis attributable to the dsdC mutation is cyclic AMP dependent.", "contents": "Role of small molecules in regulation of D-serine deaminase synthesis. Cyclic AMP is required for optimal synthesis of D-serine deaminase synthesis from dsdO+ templates and for optimal hyperinducible synthesis from low constitutive dsdO templates both in vitro and in vivo. Neither D-serine, cyclic AMP, nor dsdC activator has an effect on expression of a high constitutive dsdO template. The synthesis of the dsdC activator itself in vitro is independent of cyclic AMP. Guanosine tetraphosphate does not have a significant effect on in vitro D-serine deaminase synthesis from dsdO+ or dsdO templates. A previously described class of dsdO mutants showing partial catabolite sensitivity of constitutive D-serine deaminase synthesis proved to be low dsdO types. They all contain a low constitutive dsdC mutation; the two effects are additive with regard to level of constitutivity, but only that portion of synthesis attributable to the dsdC mutation is cyclic AMP dependent."}
{"id": "PMID:213418", "title": "Levels of cyclic GMP in dormant, germinated, and outgrowing spores and growing and sporulating cells of Bacillus megaterium.", "content": "The level of cyclic GMP was less than one molecule per organism in dormant, germinated, and outgrowing spores of Bacillus megaterium. A significant level (approximately 8 pmol/g, dry weight) of cyclic GMP was found in early to mid-log phase cells, but the level fell to below 0.2 pmol/g, dry weight, in late-log phase and only rose slightly to approximately 0.9 pmol/g, dry weight, in stationary phare. No significant amount of cyclic GMP was detected in the growth medium at any time.", "contents": "Levels of cyclic GMP in dormant, germinated, and outgrowing spores and growing and sporulating cells of Bacillus megaterium. The level of cyclic GMP was less than one molecule per organism in dormant, germinated, and outgrowing spores of Bacillus megaterium. A significant level (approximately 8 pmol/g, dry weight) of cyclic GMP was found in early to mid-log phase cells, but the level fell to below 0.2 pmol/g, dry weight, in late-log phase and only rose slightly to approximately 0.9 pmol/g, dry weight, in stationary phare. No significant amount of cyclic GMP was detected in the growth medium at any time."}
{"id": "PMID:213419", "title": "Role of the dsdC activator in regulation of D-serine deaminase synthesis.", "content": "The activator of the D-serine deaminase operon, the product of the dsdC gene, has been partially purified. It is reasonably stable to routine purification procedures in the presence of its ligand D-serine, but not in its absence. It loses activity upon dialysis in amino acid-free buffer, but activity is completely restored upon readdition of D-serine. It apparently functions purely as an activator, no repressor function could be demonstrated at suboptimal D-serine concentration. It is a transcriptional control element. The time required for in vitro transcription of D-serine deaminase mRNA, nearly 4 min, is similar to that for beta-galactosidase. Since the beta-galactosidase monomer is a much protein, this is surprisingly long.", "contents": "Role of the dsdC activator in regulation of D-serine deaminase synthesis. The activator of the D-serine deaminase operon, the product of the dsdC gene, has been partially purified. It is reasonably stable to routine purification procedures in the presence of its ligand D-serine, but not in its absence. It loses activity upon dialysis in amino acid-free buffer, but activity is completely restored upon readdition of D-serine. It apparently functions purely as an activator, no repressor function could be demonstrated at suboptimal D-serine concentration. It is a transcriptional control element. The time required for in vitro transcription of D-serine deaminase mRNA, nearly 4 min, is similar to that for beta-galactosidase. Since the beta-galactosidase monomer is a much protein, this is surprisingly long."}
{"id": "PMID:213420", "title": "Biosynthesis and regulation of fructose-1,6-bisphosphatase and phosphofructokinase in Saccharomyces cerevisiae grown in the presence of glucose and gluconeogenic carbon sources.", "content": "The mode of synthesis and the regulation of fructose-1,6-bisphosphatase (Fbpase), a gluconeogenic enzyme, and phosphofructokinase (PFK), a glycolytic enzyme, were investigated in Saccharomyces cerevisiae after growth in the presence of different concentrations of glucose or various gluconeogenic carbon sources. The activity of FBPase appeared in the cells after the complete disappearance of glucose from the growth medium with a concomitant increase of the pH and no significant change in the levels of accumulated ethanol. The appearance of FBPase activity following glucose depletion was dependent upon the synthesis of protein. The FBPase PFK were present in glucose-, ethanol-, glycerol-, lactate-, or pyruvate-grown cells; however, the time of appearance and the levels of both these enzymes varied. The FBPase activity was always higher in 1% glucose-grown cells than in cells grown in the presence of gluconeogenic carbon sources. Phosphoglucose isomerase activity did not vary significantly. Addition of glucose to an FBPase and PFK synthesizing culture resulted in a complete loss, followed by a reappearance, of PFK activity. In the presence of cycloheximide the disappearance of glucose and the changes in the levels of FBPase and PFK were decreased significantly. It is concluded that S. cerevisiae exhibits a more efficient synthesis of FBPase after the exhaustion of glucose compared to the activity present in cells grown in the presence of exogenous gluconeogenic carbon sources. Two metabolically antagonistic enzymes, FBPase and PFK, are present during the transition phase, but not during the exponential phase, of growth, and the decay or inactivation of these enzymes in vivo may be dependent upon a glucose-induced protease activity.", "contents": "Biosynthesis and regulation of fructose-1,6-bisphosphatase and phosphofructokinase in Saccharomyces cerevisiae grown in the presence of glucose and gluconeogenic carbon sources. The mode of synthesis and the regulation of fructose-1,6-bisphosphatase (Fbpase), a gluconeogenic enzyme, and phosphofructokinase (PFK), a glycolytic enzyme, were investigated in Saccharomyces cerevisiae after growth in the presence of different concentrations of glucose or various gluconeogenic carbon sources. The activity of FBPase appeared in the cells after the complete disappearance of glucose from the growth medium with a concomitant increase of the pH and no significant change in the levels of accumulated ethanol. The appearance of FBPase activity following glucose depletion was dependent upon the synthesis of protein. The FBPase PFK were present in glucose-, ethanol-, glycerol-, lactate-, or pyruvate-grown cells; however, the time of appearance and the levels of both these enzymes varied. The FBPase activity was always higher in 1% glucose-grown cells than in cells grown in the presence of gluconeogenic carbon sources. Phosphoglucose isomerase activity did not vary significantly. Addition of glucose to an FBPase and PFK synthesizing culture resulted in a complete loss, followed by a reappearance, of PFK activity. In the presence of cycloheximide the disappearance of glucose and the changes in the levels of FBPase and PFK were decreased significantly. It is concluded that S. cerevisiae exhibits a more efficient synthesis of FBPase after the exhaustion of glucose compared to the activity present in cells grown in the presence of exogenous gluconeogenic carbon sources. Two metabolically antagonistic enzymes, FBPase and PFK, are present during the transition phase, but not during the exponential phase, of growth, and the decay or inactivation of these enzymes in vivo may be dependent upon a glucose-induced protease activity."}
{"id": "PMID:213421", "title": "Changes in composition of envelope proteins in adenylate cyclase- or cyclic AMP receptor protein-deficient mutants of Escherichia coli.", "content": "Synthesis of several envelope proteins in Escherichia coli K-12 is regulated by cyclic AMP and cyclic AMP receptor protein.", "contents": "Changes in composition of envelope proteins in adenylate cyclase- or cyclic AMP receptor protein-deficient mutants of Escherichia coli. Synthesis of several envelope proteins in Escherichia coli K-12 is regulated by cyclic AMP and cyclic AMP receptor protein."}
{"id": "PMID:213422", "title": "Binding sites for angiotensin II in human mononuclear leucocytes.", "content": "Angiotensin II binding sites were demonstrated in human mononuclear leucocytes by use of [125I]angiotensin II. The binding of [125I]angiotensin II to mononuclear leucocytes was rapid and reversible. The abilities of unlabeled compounds to displace [125I]angiotensin II were proportional to their abilities to displace labeled hormone in adrenal and smooth muscle membrane preparations. The Scatchard plot revealed two apparent orders of binding sites. The affinity constants were comparable with those for binding sites in other main target tissues of angiotensin II.", "contents": "Binding sites for angiotensin II in human mononuclear leucocytes. Angiotensin II binding sites were demonstrated in human mononuclear leucocytes by use of [125I]angiotensin II. The binding of [125I]angiotensin II to mononuclear leucocytes was rapid and reversible. The abilities of unlabeled compounds to displace [125I]angiotensin II were proportional to their abilities to displace labeled hormone in adrenal and smooth muscle membrane preparations. The Scatchard plot revealed two apparent orders of binding sites. The affinity constants were comparable with those for binding sites in other main target tissues of angiotensin II."}
{"id": "PMID:213423", "title": "Specific cleavages inflicted by venom phosphodiesterase on superhelical phiX174 DNA.", "content": "A single strand specific endonuclease, venom phosphodiesterase, acting on superhelical phiX174 DNA, inflicts at least seven specific cleavages. Six of these were located to within approximately +/-40 base-pairs by mapping with restriction endonucleases. They are at 12%, 27.4%, 42.7%, 47.5%, 76.1%, and 82.5%. All of these sites lie within regions containing runs of 16 or more base-pairs, of which 12 or more are A and T. Other similarly (A + T)-rich regions in the genome are not cleaved by the enzyme. Increasing the superhelical density of the substrate did not alter the locations of the cleavage sites. There is no correlation between the locations of the cleavage sites and the three known major promoter sites. Only two of five postulated transcription termination sites are cleaved by phosphodiesterase even though all of these terminators contain (A + T)-rich regions. The area containing the origin of viral DNA replication, which includes an (A + T)-rich sequence, is not cleaved.", "contents": "Specific cleavages inflicted by venom phosphodiesterase on superhelical phiX174 DNA. A single strand specific endonuclease, venom phosphodiesterase, acting on superhelical phiX174 DNA, inflicts at least seven specific cleavages. Six of these were located to within approximately +/-40 base-pairs by mapping with restriction endonucleases. They are at 12%, 27.4%, 42.7%, 47.5%, 76.1%, and 82.5%. All of these sites lie within regions containing runs of 16 or more base-pairs, of which 12 or more are A and T. Other similarly (A + T)-rich regions in the genome are not cleaved by the enzyme. Increasing the superhelical density of the substrate did not alter the locations of the cleavage sites. There is no correlation between the locations of the cleavage sites and the three known major promoter sites. Only two of five postulated transcription termination sites are cleaved by phosphodiesterase even though all of these terminators contain (A + T)-rich regions. The area containing the origin of viral DNA replication, which includes an (A + T)-rich sequence, is not cleaved."}
{"id": "PMID:213424", "title": "Evidence for the noninvolvement of sulfogalactosylceramide (cerebroside sulfate) in the enkephalin (opiate) receptor.", "content": "Mouse neuroblastoma clonal cell line N4TG1 has 20,000 enkephaline (opiate) receptor binding sites/cell, but contains undetectable levels of sulfogalactosylceramide as judged by quantitative and isotope-labeling studies. Mouse glioma cell lines G26-20 and G26-24 contain substantial quantities of sulfogalactosylceramide, but do not bind enkephalins. Preincubation of cells with sulfogalactosylceramide or other anionic glycosphingolipids did not enhance or induce opiate receptors. Thus, sulfogalactosylceramide is not an integral part of the opiate receptor of N4TG1 cells.", "contents": "Evidence for the noninvolvement of sulfogalactosylceramide (cerebroside sulfate) in the enkephalin (opiate) receptor. Mouse neuroblastoma clonal cell line N4TG1 has 20,000 enkephaline (opiate) receptor binding sites/cell, but contains undetectable levels of sulfogalactosylceramide as judged by quantitative and isotope-labeling studies. Mouse glioma cell lines G26-20 and G26-24 contain substantial quantities of sulfogalactosylceramide, but do not bind enkephalins. Preincubation of cells with sulfogalactosylceramide or other anionic glycosphingolipids did not enhance or induce opiate receptors. Thus, sulfogalactosylceramide is not an integral part of the opiate receptor of N4TG1 cells."}
{"id": "PMID:213425", "title": "Use of a double-headed peptide substrate to study the specificity of cAMP-dependent protein kinase and posphorylase kinase.", "content": "A peptide containing 2 seryl residues, (1)Leu(2)Ser(3)Tyr(4)Arg(5)Aly(6)Tyr(7)Ser(8)Leu, was chemically synthesized and used as a substrate for phosphorylase kinase and cyclic AMP-dependent protein kinase. The sequence, TryArgGlyTyr, makes up a beta turn in the native protein. Phosphorylase kinase was found to phosphorylate specifically seryl residue2 and protein kinase seryl residue7. Km and Vmax values were obtained and compared with natural substrates. The differences in the specificity of the two enzymes might be explained by a different requirement for organized structure. As a working hypothesis, it is suggested the results could be explained if the two enzymes interacted with seryl residues at different sides of a beta turn.", "contents": "Use of a double-headed peptide substrate to study the specificity of cAMP-dependent protein kinase and posphorylase kinase. A peptide containing 2 seryl residues, (1)Leu(2)Ser(3)Tyr(4)Arg(5)Aly(6)Tyr(7)Ser(8)Leu, was chemically synthesized and used as a substrate for phosphorylase kinase and cyclic AMP-dependent protein kinase. The sequence, TryArgGlyTyr, makes up a beta turn in the native protein. Phosphorylase kinase was found to phosphorylate specifically seryl residue2 and protein kinase seryl residue7. Km and Vmax values were obtained and compared with natural substrates. The differences in the specificity of the two enzymes might be explained by a different requirement for organized structure. As a working hypothesis, it is suggested the results could be explained if the two enzymes interacted with seryl residues at different sides of a beta turn."}
{"id": "PMID:213426", "title": "Interchange of apoprotein components between the human plasma high density lipoprotein subclasses HDL2 and HDL3 in vitro.", "content": "The major apoproteins of human high density lipoproteins (HDL) labeled with 125I have been shown to exchange between the two major HDL subclasses HDL2 and HDL3 in vitro. This bidirectional exchange process is inhibited by cross-linking with bifunctional reagents and is apparently dependent upon the formation of collision complexes. This exchange has been demonstrated both when the subclasses of HDL are free in solution and also when one of them is covalently bound to Sepharose. Using system involving Sepharose-bound HDL, it could be shown that not only free apoprotein molecules but subunits consisting of lipid-apoprotein combinations were exchanged between HDL2 and HDL3. The rate of exchange in these processes is significant in the lifetime of the protein particles in vivo equalling approximately 2.5% per h for apoprotein exchange. These experiments suggest that there is a dynamic relationship between HDL2 and HDL3 even though each of them exists alone in vitro as stable separate entities; when they are placed together in solution significant interaction occurs between the particles. Apoprotein exchange occurs between HDL2:HDL2 and HDL3:HDL3 as well as between HDL2 and HDL3 molecules. These data also suggest that the interconversion of HDL2 and HDL3 may be affected by the availability of lipids.", "contents": "Interchange of apoprotein components between the human plasma high density lipoprotein subclasses HDL2 and HDL3 in vitro. The major apoproteins of human high density lipoproteins (HDL) labeled with 125I have been shown to exchange between the two major HDL subclasses HDL2 and HDL3 in vitro. This bidirectional exchange process is inhibited by cross-linking with bifunctional reagents and is apparently dependent upon the formation of collision complexes. This exchange has been demonstrated both when the subclasses of HDL are free in solution and also when one of them is covalently bound to Sepharose. Using system involving Sepharose-bound HDL, it could be shown that not only free apoprotein molecules but subunits consisting of lipid-apoprotein combinations were exchanged between HDL2 and HDL3. The rate of exchange in these processes is significant in the lifetime of the protein particles in vivo equalling approximately 2.5% per h for apoprotein exchange. These experiments suggest that there is a dynamic relationship between HDL2 and HDL3 even though each of them exists alone in vitro as stable separate entities; when they are placed together in solution significant interaction occurs between the particles. Apoprotein exchange occurs between HDL2:HDL2 and HDL3:HDL3 as well as between HDL2 and HDL3 molecules. These data also suggest that the interconversion of HDL2 and HDL3 may be affected by the availability of lipids."}
{"id": "PMID:213427", "title": "Electronic state of heme in cytochrome oxidase III. The magnetic susceptibility of beef heart cytochrome oxidase and some of its derivatives from 7-200 K. Direct evidence for an antiferromagnetically coupled Fe (III)/Cu (II) pair.", "content": "The temperature dependence of the paramagnetic susceptibility of cytochrome oxidase and some of its derivatives has been measured from 7 to 200 K. The results obtained for the fully oxidized (resting) enzyme correspond exactly to the requirements of the model recently proposed by Palmer et al. (Palmer, G., Babcock, G. T., and Vickery, L. E. (1976) Proc. Natl. Acad. Sci. U. S. A. 73, 2206-2210) in which the enzyme possesses two magnetically isolated spin S = 1/2 centers and a spin-coupled S = 2 center. The S = 2 center paramagnetism has been interpreted as arising from a [cytochrome a33+(S = 5/2)--Cuu2+(S = 1/2)] antiferromagnetically coupled iron.copper binuclear complex of total spin S = 2 with -J greater than or equal to 200 cm-1. In addition, the wide temperature range used in the present studies has permitted an analysis of present and other available data (T less than 4K measurements) which readily accommodates results from this and other laboratories (Moss, T.H., Shapiro, E., King, T.E., Beinert, H., and Hartzell, C. R. (1978) J. Biol. Chem 253, 8072-8073) so that a fully consistent picture of the magnetic centers in cytochrome oxidase now appears to be available. Furthermore, anomalous magnetic behavior for the oxidized enzyme.cyanide complex has been interpreted in terms of an antiferromagnetic exchange interaction operating in the binuclear complex [cytochrome a33+.CN-(S = 1/2)--Cuu2+(S = 1/2)] with -J congruent to 40 cm-1. A structural model for the [cytochrome a3(3+)-bridge-CUu2+] center is advanced in which an imidazolate ion serves as the bridging ligand in a manner similar to that found in superoxide dismutase.", "contents": "Electronic state of heme in cytochrome oxidase III. The magnetic susceptibility of beef heart cytochrome oxidase and some of its derivatives from 7-200 K. Direct evidence for an antiferromagnetically coupled Fe (III)/Cu (II) pair. The temperature dependence of the paramagnetic susceptibility of cytochrome oxidase and some of its derivatives has been measured from 7 to 200 K. The results obtained for the fully oxidized (resting) enzyme correspond exactly to the requirements of the model recently proposed by Palmer et al. (Palmer, G., Babcock, G. T., and Vickery, L. E. (1976) Proc. Natl. Acad. Sci. U. S. A. 73, 2206-2210) in which the enzyme possesses two magnetically isolated spin S = 1/2 centers and a spin-coupled S = 2 center. The S = 2 center paramagnetism has been interpreted as arising from a [cytochrome a33+(S = 5/2)--Cuu2+(S = 1/2)] antiferromagnetically coupled iron.copper binuclear complex of total spin S = 2 with -J greater than or equal to 200 cm-1. In addition, the wide temperature range used in the present studies has permitted an analysis of present and other available data (T less than 4K measurements) which readily accommodates results from this and other laboratories (Moss, T.H., Shapiro, E., King, T.E., Beinert, H., and Hartzell, C. R. (1978) J. Biol. Chem 253, 8072-8073) so that a fully consistent picture of the magnetic centers in cytochrome oxidase now appears to be available. Furthermore, anomalous magnetic behavior for the oxidized enzyme.cyanide complex has been interpreted in terms of an antiferromagnetic exchange interaction operating in the binuclear complex [cytochrome a33+.CN-(S = 1/2)--Cuu2+(S = 1/2)] with -J congruent to 40 cm-1. A structural model for the [cytochrome a3(3+)-bridge-CUu2+] center is advanced in which an imidazolate ion serves as the bridging ligand in a manner similar to that found in superoxide dismutase."}
{"id": "PMID:213428", "title": "The magnetic susceptibility of cytochrome oxidase in the 4.2-1.5 K range.", "content": "Sixteen low temperature measurements on eight independent cytochrome oxidase samples from two separate laboratories have yielded magnetic susceptibility data compatible with a model of spin-coupled iron and copper ions, as presented in the preceding paper (Tweedle, M.F., Wilson, L.J., Garc\u00eda-I\u00f1iguez, L., Babcock, G. T., and Palmer, G. (1978) J. Biol. Chem. 253, 8065-8071). The data in the 1.5-77 K range match those attained at higher temperatures and the predictions of the spin-coupled model. Measurements on reduced samples confirm the high spin nature of one iron atom. No obvious uncoupling of the antiferromagnetic Fe-Cu interaction is detected in partly reduced samples.", "contents": "The magnetic susceptibility of cytochrome oxidase in the 4.2-1.5 K range. Sixteen low temperature measurements on eight independent cytochrome oxidase samples from two separate laboratories have yielded magnetic susceptibility data compatible with a model of spin-coupled iron and copper ions, as presented in the preceding paper (Tweedle, M.F., Wilson, L.J., Garc\u00eda-I\u00f1iguez, L., Babcock, G. T., and Palmer, G. (1978) J. Biol. Chem. 253, 8065-8071). The data in the 1.5-77 K range match those attained at higher temperatures and the predictions of the spin-coupled model. Measurements on reduced samples confirm the high spin nature of one iron atom. No obvious uncoupling of the antiferromagnetic Fe-Cu interaction is detected in partly reduced samples."}
{"id": "PMID:213430", "title": "Transport of phosphate in membrane vesicles from mouse fibroblasts transformed by simian virus 40.", "content": "Membrane vesicles were prepared from mouse fibroblasts transformed by SV40 virus (SV3T3). Following disruption of the cells by nitrogen cavitation, the membrane vesicles were obtained by differential centrifugation. As measured by enzyme markers, they consist mainly of membrane from the plasma membrane and smooth and rough endoplasmic reticulum. The vesicles transport Pi by two separate, mediated systems: one is independent of Na+, and the other is secondary active transport driven by a Na+ gradient. Electrical and chemical energy can be provided by a Na+ gradient to drive the concentrative uptake of Pi by the vesicles, one or both forces being used to energize transport. Evidence is provided that both the electrical and chemical potentials produced by the asymmetric distribution of Na+ across the membrane of SV3T3 membrane vesicles are utilized to concentrate phosphate in the vesicles. Phosphate transport by the vesicles cannot be accounted for by a small contamination of this fraction with mitochondria (1 to 4%). The Pi transport properties of the membrane vesicles differ from those of the fraction enriched in mitochondria in the following respects: their kinetic properties, and their responses to a Na+ gradient, N-ethylmaleimide, mersalyl, and succinate/acetate. However, the membrane vesicles share some properties of Pi transport with mitochondria. Cyanide, azide, oligomycin, 2,4-dinitrophenol, and carbonyl cyanide m-cholophenylhydrazone, inhibitors of Pi transport by mitochondria, also inhibit membrane vesicle, Pi transport. The vesicles retain all the features of Pi transport by SV3T3 cells that have been examined. They provide a simplified system for a determination of the details of the mechanism of Pi transport under conditions where transport is dissociated from intracellular reactions and in the presence of a defined electrochemical driving force.", "contents": "Transport of phosphate in membrane vesicles from mouse fibroblasts transformed by simian virus 40. Membrane vesicles were prepared from mouse fibroblasts transformed by SV40 virus (SV3T3). Following disruption of the cells by nitrogen cavitation, the membrane vesicles were obtained by differential centrifugation. As measured by enzyme markers, they consist mainly of membrane from the plasma membrane and smooth and rough endoplasmic reticulum. The vesicles transport Pi by two separate, mediated systems: one is independent of Na+, and the other is secondary active transport driven by a Na+ gradient. Electrical and chemical energy can be provided by a Na+ gradient to drive the concentrative uptake of Pi by the vesicles, one or both forces being used to energize transport. Evidence is provided that both the electrical and chemical potentials produced by the asymmetric distribution of Na+ across the membrane of SV3T3 membrane vesicles are utilized to concentrate phosphate in the vesicles. Phosphate transport by the vesicles cannot be accounted for by a small contamination of this fraction with mitochondria (1 to 4%). The Pi transport properties of the membrane vesicles differ from those of the fraction enriched in mitochondria in the following respects: their kinetic properties, and their responses to a Na+ gradient, N-ethylmaleimide, mersalyl, and succinate/acetate. However, the membrane vesicles share some properties of Pi transport with mitochondria. Cyanide, azide, oligomycin, 2,4-dinitrophenol, and carbonyl cyanide m-cholophenylhydrazone, inhibitors of Pi transport by mitochondria, also inhibit membrane vesicle, Pi transport. The vesicles retain all the features of Pi transport by SV3T3 cells that have been examined. They provide a simplified system for a determination of the details of the mechanism of Pi transport under conditions where transport is dissociated from intracellular reactions and in the presence of a defined electrochemical driving force."}
{"id": "PMID:213431", "title": "Preparation of crystalline carbamyl phosphate synthetase-I from frog liver.", "content": "Ammonia- and N-acetylglutamate-dependent carbamyl phosphate synthetase-I (EC 2.7.2.5), the mitchondrial enzyme involved in the initial step of urea biosynthesis, was purified to homogeneity from frog liver and crystallized. The purification involved extraction of a particulate fraction with cetyltrimethylammonium  bromide in the presence of the protease inhibitors antipain, leupeptin, chymostatin, and pepstatin; acetone precipitation; and affinity chromatography with Cibacron blue F3GA-coupled agarose. The enzyme was adsorbed to the gel at pH 8.3 in the presence of 5 mM MgCl2 and eluted with magnesoum-free buffer. The enzyme crystallized as either elongated, thin, rectangular plates or as clusters of small crystals from 37 to 40% saturated ammonium sulfate. The enzyme moved as a single polypeptide band on sodium dodecyl sulfate/polyacrylamide gel electrophoresis with a molecular weight of 160,000. In the absence of protease inhibitors, proteolysis of the enzyme occurred with the formation of an enzymatically active fragment with a subunit molecular weight of 139,000.", "contents": "Preparation of crystalline carbamyl phosphate synthetase-I from frog liver. Ammonia- and N-acetylglutamate-dependent carbamyl phosphate synthetase-I (EC 2.7.2.5), the mitchondrial enzyme involved in the initial step of urea biosynthesis, was purified to homogeneity from frog liver and crystallized. The purification involved extraction of a particulate fraction with cetyltrimethylammonium  bromide in the presence of the protease inhibitors antipain, leupeptin, chymostatin, and pepstatin; acetone precipitation; and affinity chromatography with Cibacron blue F3GA-coupled agarose. The enzyme was adsorbed to the gel at pH 8.3 in the presence of 5 mM MgCl2 and eluted with magnesoum-free buffer. The enzyme crystallized as either elongated, thin, rectangular plates or as clusters of small crystals from 37 to 40% saturated ammonium sulfate. The enzyme moved as a single polypeptide band on sodium dodecyl sulfate/polyacrylamide gel electrophoresis with a molecular weight of 160,000. In the absence of protease inhibitors, proteolysis of the enzyme occurred with the formation of an enzymatically active fragment with a subunit molecular weight of 139,000."}
{"id": "PMID:213432", "title": "Phosphorylation of smooth muscle myosin light chain kinase by the catalytic subunit of adenosine 3': 5'-monophosphate-dependent protein kinase.", "content": "Turkey gizzard smooth muscle light chain kinase was purified by affinity chromatography on calcium dependent regulator weight of 125,000 +/- 5,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When myosin light chain kinase is incubated with the catalytic subunit of cyclic AMP-dependent protein kinase, 1 mol of phosphate is incorporated per mol of myosin kinase. Brief tryptic digestion of the 32P-labeled myosin kinase liberates a single radioactive peptide with a molecular weight of approximately 22,000. Phosphorylation of myosin kinase results in a 2-fold decrease in the rate at which the enzyme phosphorylates the 20,000-dalton light chain of smooth muscle myosin. These results suggest that cyclic AMP has a direct effect on actin-myosin interaction in smooth muscle.", "contents": "Phosphorylation of smooth muscle myosin light chain kinase by the catalytic subunit of adenosine 3': 5'-monophosphate-dependent protein kinase. Turkey gizzard smooth muscle light chain kinase was purified by affinity chromatography on calcium dependent regulator weight of 125,000 +/- 5,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When myosin light chain kinase is incubated with the catalytic subunit of cyclic AMP-dependent protein kinase, 1 mol of phosphate is incorporated per mol of myosin kinase. Brief tryptic digestion of the 32P-labeled myosin kinase liberates a single radioactive peptide with a molecular weight of approximately 22,000. Phosphorylation of myosin kinase results in a 2-fold decrease in the rate at which the enzyme phosphorylates the 20,000-dalton light chain of smooth muscle myosin. These results suggest that cyclic AMP has a direct effect on actin-myosin interaction in smooth muscle."}
{"id": "PMID:213433", "title": "Metabolite control of L-fucose utilization.", "content": "Thyroid fucokinase is responsive to a number of metabolites which might serve in a regulatory capacity. In addition to inhibition by ADP and stimulation by GMP, fucokinase responds selectively to a series of nucleotide sugars. Of those studied, only guanine nucleotide sugars moderate the activity of the enzyme. GDP-alpha-D-mannose, GDP-alpha-D-glucose, GDP-alpha-D-rhamnose, and GDP-alpha-L-fucose on the other hand is strongly inhibitory. In the case of GDP-alpha-D-mannose stimulation, a physiological role seems possible, but the rationale is not entirely clear. The effects of GDP-beta-L-fucose, on the other hand may represent physiological control effected through feedback inhibition by and end product.", "contents": "Metabolite control of L-fucose utilization. Thyroid fucokinase is responsive to a number of metabolites which might serve in a regulatory capacity. In addition to inhibition by ADP and stimulation by GMP, fucokinase responds selectively to a series of nucleotide sugars. Of those studied, only guanine nucleotide sugars moderate the activity of the enzyme. GDP-alpha-D-mannose, GDP-alpha-D-glucose, GDP-alpha-D-rhamnose, and GDP-alpha-L-fucose on the other hand is strongly inhibitory. In the case of GDP-alpha-D-mannose stimulation, a physiological role seems possible, but the rationale is not entirely clear. The effects of GDP-beta-L-fucose, on the other hand may represent physiological control effected through feedback inhibition by and end product."}
{"id": "PMID:213434", "title": "Amino acid sequence of a peptide containing an essential cysteine residue of Escherichia coli GMP synthetase.", "content": "The amino acid sequence of a 51-residue tryptic peptide of citraconylated [1-14C]carboxamidomethyl-labeled Escherichia coli GMP synthetase was determined by sequenator analyses of the intact peptide and fragments obtained by cleavage of the peptide with cyanogen bromide, trypsin, and Staphylcoccus aureus strain V8 protease. The cysteine residue of this peptide fragment is essential for glutamine-dependent GMP synthesis activity and is implicated in formation of a hypothetical covalent glutamyl-enzyme intermediate. There is essentially cysteine-containing regions of two other glutamine amidotransferases, Pseudomonas putida anthranilate synthetase Component II and chicken liver formylglycinamide ribonucleotide amidotransferase. There is, however, a cluster of amino acids with \"antipathy\" for helix formation and a \"nonessential\" cysteine of anthranilate synthetase Component II.", "contents": "Amino acid sequence of a peptide containing an essential cysteine residue of Escherichia coli GMP synthetase. The amino acid sequence of a 51-residue tryptic peptide of citraconylated [1-14C]carboxamidomethyl-labeled Escherichia coli GMP synthetase was determined by sequenator analyses of the intact peptide and fragments obtained by cleavage of the peptide with cyanogen bromide, trypsin, and Staphylcoccus aureus strain V8 protease. The cysteine residue of this peptide fragment is essential for glutamine-dependent GMP synthesis activity and is implicated in formation of a hypothetical covalent glutamyl-enzyme intermediate. There is essentially cysteine-containing regions of two other glutamine amidotransferases, Pseudomonas putida anthranilate synthetase Component II and chicken liver formylglycinamide ribonucleotide amidotransferase. There is, however, a cluster of amino acids with \"antipathy\" for helix formation and a \"nonessential\" cysteine of anthranilate synthetase Component II."}
{"id": "PMID:213435", "title": "Effect of adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate on RNA release from isolated nuclei.", "content": "The addition of physiological concentrations of either cAMP or cGMP stimulated the release of RNA from isolated prelabeled rat liver nuclei to a fortified cytosol in a cell-free system. The released RNA was shown to be primarily mRNA by its binding to oligo(dT)-cellulose and its sedimentation profile. Treatment of rats with cAMP or cGMP 30 min prior to the preparation of cyclic nucleotides on the cell-free system. Cyclic nucleotides stimulation of RNA release occurred in systems prepared from resting rat liver, Novikoff hepatoma, and Morris hepatoma 5123D, but not the 18-h regenerating liver. The response of the cell-free system to added cyclic nucleotides reflected the in vivo concentration of these substances in the tissues from which the system was prepared. Those with high in vivo levels were not stimulated while those with lower levels did respond to added cyclic nucleotides. Neither cAMP nor cGMP had an appreciable effect on rRNA release.", "contents": "Effect of adenosine 3':5'-monophosphate and guanosine 3':5'-monophosphate on RNA release from isolated nuclei. The addition of physiological concentrations of either cAMP or cGMP stimulated the release of RNA from isolated prelabeled rat liver nuclei to a fortified cytosol in a cell-free system. The released RNA was shown to be primarily mRNA by its binding to oligo(dT)-cellulose and its sedimentation profile. Treatment of rats with cAMP or cGMP 30 min prior to the preparation of cyclic nucleotides on the cell-free system. Cyclic nucleotides stimulation of RNA release occurred in systems prepared from resting rat liver, Novikoff hepatoma, and Morris hepatoma 5123D, but not the 18-h regenerating liver. The response of the cell-free system to added cyclic nucleotides reflected the in vivo concentration of these substances in the tissues from which the system was prepared. Those with high in vivo levels were not stimulated while those with lower levels did respond to added cyclic nucleotides. Neither cAMP nor cGMP had an appreciable effect on rRNA release."}
{"id": "PMID:213436", "title": "Stimulation of the protein synthetic process by adenosine 3':5'-monophosphate and hexose phosphates in gel-filtered rabbit reticulocyte lysates.", "content": "The addition of 0.167 to 4.0 mM cAMP to gel-filtered rabbit reticulocyte lysates stimulates the initial rate and the extent of polypeptide synthesis. The stimulation is at the initiation step of polypeptide synthesis as measured by the (i) increased dipeptide, methionyl-valine, accumulation in the presence of the specific initiation inhibitor, pactamycin, and (ii) increased formation of the 40 S and 80 S initiation complex when gel-filtered lysates are incubated with [35S]Met-tRNAFMet. Furthermore, a synergistic stimulation of protein synthesis is observed when cAMP and hexose phosphates (which alone elicit a 1.8-fold stimulation of protein synthesis) are added simultaneously to gel-filtered rabbit reticulocyte lysates. These results indicate that cAMP and hexose phosphates are both essential to maintain the high rate of initiation.", "contents": "Stimulation of the protein synthetic process by adenosine 3':5'-monophosphate and hexose phosphates in gel-filtered rabbit reticulocyte lysates. The addition of 0.167 to 4.0 mM cAMP to gel-filtered rabbit reticulocyte lysates stimulates the initial rate and the extent of polypeptide synthesis. The stimulation is at the initiation step of polypeptide synthesis as measured by the (i) increased dipeptide, methionyl-valine, accumulation in the presence of the specific initiation inhibitor, pactamycin, and (ii) increased formation of the 40 S and 80 S initiation complex when gel-filtered lysates are incubated with [35S]Met-tRNAFMet. Furthermore, a synergistic stimulation of protein synthesis is observed when cAMP and hexose phosphates (which alone elicit a 1.8-fold stimulation of protein synthesis) are added simultaneously to gel-filtered rabbit reticulocyte lysates. These results indicate that cAMP and hexose phosphates are both essential to maintain the high rate of initiation."}
{"id": "PMID:213437", "title": "Phosphoglycerate mutase. Kinetics and effects of salts on the mutase and bisphosphoglycerate phosphatase activities of the enzyme from chicken breast muscle.", "content": "The steady state kinetics and effects of salts on chicken breast phosphoglycerate mutase have been examined. The enzyme can catalyze three phosphoryl transfer reactions: mutase, bisphosphoglycerate phosphatase, and bisphosphoglycerate synthase. The mutase rate was measured in the favorable direction (Keq = glycerate-3-P/glycerate-2-P approximately equal to 12) using [2T]glycerate-2-P as substrate. The bisphosphoglycerate phosphatase activity was studied in the presence of the activator, glycolate-2-P. The latter is an analog of the glycerate-P's and appears to act as an abortive mutase substrate. The kinetic pattern obtained with both activities is that of a ping-pong mechanism with inhibition by the second substrate occurring at a lower concentration than the Km value for that substrate. The kinetic parameters for the mutase determined in 50 mM N-[tris(hydroxymethyl)methyl-2-amino]ethanesulfonate (TES)/sodium buffer containing 0.1 M KCl, pH 7.5, 25 degrees C are: Km glycerate-2,3-P2, 0.069 micron; Km glycerate-2-P, 14 micron; Km glycerate-3-P approximately 200 micron; Ki glycerate-2-P, 4 micron. The kinetic parameters for the phosphatase reaction in 50 mM triethanolamine/Cl- buffer, pH 7.5, 25 degrees C are: Km glycerate-2,3-P2, 0.065 micron:Km glycolate-2P, 479 micron; Ki glycolate-2-P, 135 micron. The enzyme is sensitive to changes in the ionic environment. Increasing salt concentrations activate the phosphatase in the presence of glycolate-2-P by decreasing the apparent Km of glycerate-2,3-P2. The effects are due to the anionic component and Cl- greater than acetate greater than TES. The same salts are competitive inhibitors with respect to glycolate-2-P. With high levels of KCl that produce a 30-fold decrease in the apparent maximal velocity due to competition with glycolate-2-P, the Km of glycerate-2,3-P2 remains low. These observations lead us to postulate that each monophosphoglycerate substrate has a separate site on the enzyme and that glycerate-2,3-P2 can bind to either site. The binding of anions to one site of the nonphosphorylated enzyme allows an increase in the on and off rates of glycerate-2,3-P2 at the alternate site. Salts inhibit the mutase reaction. The Km of glycerate-2,3-P2 is increased as is that of glycerate-2-P. The effect on the Km of glycerate-2,3-P2 is attributed to an increase in the off rate/on rate ratio for glycerate-2,3-P2. The bisphosphoglycerate synthase reaction is shown to require added glycerate-3-P. The equilibrium between enzyme and glycerate-1,3-P2 is favorable (Kdiss less than or equal 7 X 10(-8) M) and suggests that in the absence of a separate synthase this reaction may have functional significance.", "contents": "Phosphoglycerate mutase. Kinetics and effects of salts on the mutase and bisphosphoglycerate phosphatase activities of the enzyme from chicken breast muscle. The steady state kinetics and effects of salts on chicken breast phosphoglycerate mutase have been examined. The enzyme can catalyze three phosphoryl transfer reactions: mutase, bisphosphoglycerate phosphatase, and bisphosphoglycerate synthase. The mutase rate was measured in the favorable direction (Keq = glycerate-3-P/glycerate-2-P approximately equal to 12) using [2T]glycerate-2-P as substrate. The bisphosphoglycerate phosphatase activity was studied in the presence of the activator, glycolate-2-P. The latter is an analog of the glycerate-P's and appears to act as an abortive mutase substrate. The kinetic pattern obtained with both activities is that of a ping-pong mechanism with inhibition by the second substrate occurring at a lower concentration than the Km value for that substrate. The kinetic parameters for the mutase determined in 50 mM N-[tris(hydroxymethyl)methyl-2-amino]ethanesulfonate (TES)/sodium buffer containing 0.1 M KCl, pH 7.5, 25 degrees C are: Km glycerate-2,3-P2, 0.069 micron; Km glycerate-2-P, 14 micron; Km glycerate-3-P approximately 200 micron; Ki glycerate-2-P, 4 micron. The kinetic parameters for the phosphatase reaction in 50 mM triethanolamine/Cl- buffer, pH 7.5, 25 degrees C are: Km glycerate-2,3-P2, 0.065 micron:Km glycolate-2P, 479 micron; Ki glycolate-2-P, 135 micron. The enzyme is sensitive to changes in the ionic environment. Increasing salt concentrations activate the phosphatase in the presence of glycolate-2-P by decreasing the apparent Km of glycerate-2,3-P2. The effects are due to the anionic component and Cl- greater than acetate greater than TES. The same salts are competitive inhibitors with respect to glycolate-2-P. With high levels of KCl that produce a 30-fold decrease in the apparent maximal velocity due to competition with glycolate-2-P, the Km of glycerate-2,3-P2 remains low. These observations lead us to postulate that each monophosphoglycerate substrate has a separate site on the enzyme and that glycerate-2,3-P2 can bind to either site. The binding of anions to one site of the nonphosphorylated enzyme allows an increase in the on and off rates of glycerate-2,3-P2 at the alternate site. Salts inhibit the mutase reaction. The Km of glycerate-2,3-P2 is increased as is that of glycerate-2-P. The effect on the Km of glycerate-2,3-P2 is attributed to an increase in the off rate/on rate ratio for glycerate-2,3-P2. The bisphosphoglycerate synthase reaction is shown to require added glycerate-3-P. The equilibrium between enzyme and glycerate-1,3-P2 is favorable (Kdiss less than or equal 7 X 10(-8) M) and suggests that in the absence of a separate synthase this reaction may have functional significance."}
{"id": "PMID:213439", "title": "Two Epstein-Barr virus-associated DNA polymerase activities.", "content": "We have partially purified and characterized two separate DNA polymerase activities associated with Epstein-Barr virus (EB virus). One activity is present in EB virus producer cell lines but not in nonproducer or negative cell lines. It adheres more strongly to DEAE-cellulose than any host cell enzymes, eluting at 210 to 270 mM potassium phosphate buffer. Further elution from phosphocellulose and sedimentation in glycerol gradients yields an enzyme purified 900-fold with an S value of 8.3. The second DNA polymerase activity co-purifies with EB viral particles, elutes at low salt from DEAE-cellulose (40 to 60 mM potassium phosphate buffer) and phosphocellulose (100 mM), and has an S value of 9.5 on glycerol gradient sedimentation. These two enzymes are referred to for convenience as the EB virus-induced DNA polymerase and the EB virion-associated DNA polymerase. The EB virus-induced polymerase can be distinguished from host alpha, beta, and the virion-associated polymerase in 1) being resistant to salt inhibition, 2) having a more basic pH optima in Tris buffer (pH 9.5), and 3) having a 10-fold lower saturating concentration for the activated DNA template. The EB virion-associated polymerase is distinguished from host alpha, beta, and the EB virus-induced polymerase, because it cannot utilize synthetic deoxy- and ribohomopolymer primer-templates in place of the activated calf thymus DNA template in DNA polymerase assays. Neither of the EB virus-associated polymerases can copy the ribohomopolymers dT10poly(rA) or dG12-18(poly(rC) efficiently and therefore can be distinguished from host gamma polymerase and reverse transcriptase. The activity of the EB virus-induced and virion-associated polymerases are unaffected both by antibody to alpha polymerase, and by antiserum with high antibody titers to EB early antigen and viral capsid antigen.", "contents": "Two Epstein-Barr virus-associated DNA polymerase activities. We have partially purified and characterized two separate DNA polymerase activities associated with Epstein-Barr virus (EB virus). One activity is present in EB virus producer cell lines but not in nonproducer or negative cell lines. It adheres more strongly to DEAE-cellulose than any host cell enzymes, eluting at 210 to 270 mM potassium phosphate buffer. Further elution from phosphocellulose and sedimentation in glycerol gradients yields an enzyme purified 900-fold with an S value of 8.3. The second DNA polymerase activity co-purifies with EB viral particles, elutes at low salt from DEAE-cellulose (40 to 60 mM potassium phosphate buffer) and phosphocellulose (100 mM), and has an S value of 9.5 on glycerol gradient sedimentation. These two enzymes are referred to for convenience as the EB virus-induced DNA polymerase and the EB virion-associated DNA polymerase. The EB virus-induced polymerase can be distinguished from host alpha, beta, and the virion-associated polymerase in 1) being resistant to salt inhibition, 2) having a more basic pH optima in Tris buffer (pH 9.5), and 3) having a 10-fold lower saturating concentration for the activated DNA template. The EB virion-associated polymerase is distinguished from host alpha, beta, and the EB virus-induced polymerase, because it cannot utilize synthetic deoxy- and ribohomopolymer primer-templates in place of the activated calf thymus DNA template in DNA polymerase assays. Neither of the EB virus-associated polymerases can copy the ribohomopolymers dT10poly(rA) or dG12-18(poly(rC) efficiently and therefore can be distinguished from host gamma polymerase and reverse transcriptase. The activity of the EB virus-induced and virion-associated polymerases are unaffected both by antibody to alpha polymerase, and by antiserum with high antibody titers to EB early antigen and viral capsid antigen."}
{"id": "PMID:213442", "title": "Epstein-Barr virus in somatic cell hybrids between mouse cells and human nasopharyngeal carcinoma cells.", "content": "Somatic cell hybrids between mouse cells and cells derived directly from NPC biopsies were produced in order to study the association of the Epstein-Barr virus (EBV) genome and the expression of Epstein-Barr nuclear antigen (EBNA) with the human chromosome(s). All attempts to correlate the presence of EBV-DNA and the expression of EBNA with the presence of a particular human chromosome(s) showed that the segregation of EBV-DNA or of EBNA and human chromosomes was dysconcordant. The data, therefore, suggest that in the hybrids studied the presence of EBA-DNA is not determined by the presence of a specific human chromosome.", "contents": "Epstein-Barr virus in somatic cell hybrids between mouse cells and human nasopharyngeal carcinoma cells. Somatic cell hybrids between mouse cells and cells derived directly from NPC biopsies were produced in order to study the association of the Epstein-Barr virus (EBV) genome and the expression of Epstein-Barr nuclear antigen (EBNA) with the human chromosome(s). All attempts to correlate the presence of EBV-DNA and the expression of EBNA with the presence of a particular human chromosome(s) showed that the segregation of EBV-DNA or of EBNA and human chromosomes was dysconcordant. The data, therefore, suggest that in the hybrids studied the presence of EBA-DNA is not determined by the presence of a specific human chromosome."}
{"id": "PMID:213445", "title": "Relationship between the accumulation of pituitary growth hormone and nuclear occupancy by triiodothyronine in the rat.", "content": "Studies were undertaken in hypothyroid rats in an effort to define the kinetics of growth hormone (GH) accumulation in response to i.v. pulse injections of triiodothyronine (T(3)) and to calculate the relationship between nuclear occupancy by T(3) and the instantaneous rate of accumulation of pituitary GH. Results were contrasted to the findings in previous studies of the induction of hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and malic enzyme (ME) by T(3). The dose of T(3) required to achieve half-maximal accumulation of GH in 24 h was 0.6 mug/100 g body wt, a value 15-fold less than the half-maximal dose for alpha-GPD and ME induction at a comparable time after injection. Although significant increase in pituitary GH were evident as early as 3 h after injection of maximally effective doses of T(3), the rate of increase became linear only 12 h after injection. After achievement of peak values, the pituitary content of GH decayed with a similar terminal t((1/2)) of 3.9 days and 4.1 days in two groups of animals injected with a single dose of 1.0 and 50 mug T(3)/100 g body wt, respectively. In vivo isotopic displacement studies carried out at the equilibrium time point indicated that the pituitary nuclear binding capacity was 5.5 ng T(3)/g tissue and that the plasma concentration at which one-half of the nuclear sites are occupied is 1.0 ng/ml. Nuclear occupancy as a function of time was calculated from the estimated plasma T(3) concentration after injection of the dose and the half-occupancy plasma concentration. These data were then analyzed by application of the mathematical model previously developed to ascertain the relationship between nuclear occupancy and the rate of hepatic enzyme induction. Results indicated that the pituitary nuclear occupancy-response relationship was generally linear, in marked contrast to the highly amplified relationship between nuclear occupancy and the response of ME and alpha-GPD to T(3) in the liver. In supplementary experiments, euthyroid rats received daily injections of 200 mug of T(3) for 7 days to keep nuclear sites nearly saturated for the duration of the experiment. No significant increase in the pituitary GH content above euthyroid base-line levels was noted. This also contrasts with the marked increase above euthyroid levels in alpha-GPD and ME observed in previous studies. Our findings suggest the existence of major differences between the specific mechanisms which lead to the induction of pituitary GH and the hepatic enzymes by T(3).", "contents": "Relationship between the accumulation of pituitary growth hormone and nuclear occupancy by triiodothyronine in the rat. Studies were undertaken in hypothyroid rats in an effort to define the kinetics of growth hormone (GH) accumulation in response to i.v. pulse injections of triiodothyronine (T(3)) and to calculate the relationship between nuclear occupancy by T(3) and the instantaneous rate of accumulation of pituitary GH. Results were contrasted to the findings in previous studies of the induction of hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and malic enzyme (ME) by T(3). The dose of T(3) required to achieve half-maximal accumulation of GH in 24 h was 0.6 mug/100 g body wt, a value 15-fold less than the half-maximal dose for alpha-GPD and ME induction at a comparable time after injection. Although significant increase in pituitary GH were evident as early as 3 h after injection of maximally effective doses of T(3), the rate of increase became linear only 12 h after injection. After achievement of peak values, the pituitary content of GH decayed with a similar terminal t((1/2)) of 3.9 days and 4.1 days in two groups of animals injected with a single dose of 1.0 and 50 mug T(3)/100 g body wt, respectively. In vivo isotopic displacement studies carried out at the equilibrium time point indicated that the pituitary nuclear binding capacity was 5.5 ng T(3)/g tissue and that the plasma concentration at which one-half of the nuclear sites are occupied is 1.0 ng/ml. Nuclear occupancy as a function of time was calculated from the estimated plasma T(3) concentration after injection of the dose and the half-occupancy plasma concentration. These data were then analyzed by application of the mathematical model previously developed to ascertain the relationship between nuclear occupancy and the rate of hepatic enzyme induction. Results indicated that the pituitary nuclear occupancy-response relationship was generally linear, in marked contrast to the highly amplified relationship between nuclear occupancy and the response of ME and alpha-GPD to T(3) in the liver. In supplementary experiments, euthyroid rats received daily injections of 200 mug of T(3) for 7 days to keep nuclear sites nearly saturated for the duration of the experiment. No significant increase in the pituitary GH content above euthyroid base-line levels was noted. This also contrasts with the marked increase above euthyroid levels in alpha-GPD and ME observed in previous studies. Our findings suggest the existence of major differences between the specific mechanisms which lead to the induction of pituitary GH and the hepatic enzymes by T(3)."}
{"id": "PMID:213446", "title": "Cytochemical localization of Na+, K+-ATPase in the rat hepatocyte.", "content": "The enzyme Na+,5+-ATPase was cytochemically localized in the rat hepatocyte by a modification of the Ernst potassium-dependent nitrophenyl phosphatase technique. Measurement of nitrophenol release from 50-micrometer liver slices confirmed the presence of ouabain-inhibitable nitrophenyl phosphatase activity that increased over the 30-min incubation period. Electron micrographs demonstrated that sinusoidal and lateral membrane reaction product deposition was K+-dependent, Mg++-dependent, inhibited by ouabain but not by alkaline phosphatase inhibitors, and was localized to the cytoplasmic side of the membrane. In contrast, canalicular reaction product was K+-independent, Mg++-dependent, inhibited by alkaline phosphatase inhibitors but not by ouabain, and was localized to the luminal side of the membrane. These findings indicate that Na+,K+-ATPase is localized to the sinusoidal and lateral portions of the rat hepatocyte plasma membrane and is not detectable on the bile canaliculus where alkaline phosphatase is confined. This basolateral localization of Na+,K+-ATPase is similar to that found in epithelia where secretion is also directed across the apical membrane.", "contents": "Cytochemical localization of Na+, K+-ATPase in the rat hepatocyte. The enzyme Na+,5+-ATPase was cytochemically localized in the rat hepatocyte by a modification of the Ernst potassium-dependent nitrophenyl phosphatase technique. Measurement of nitrophenol release from 50-micrometer liver slices confirmed the presence of ouabain-inhibitable nitrophenyl phosphatase activity that increased over the 30-min incubation period. Electron micrographs demonstrated that sinusoidal and lateral membrane reaction product deposition was K+-dependent, Mg++-dependent, inhibited by ouabain but not by alkaline phosphatase inhibitors, and was localized to the cytoplasmic side of the membrane. In contrast, canalicular reaction product was K+-independent, Mg++-dependent, inhibited by alkaline phosphatase inhibitors but not by ouabain, and was localized to the luminal side of the membrane. These findings indicate that Na+,K+-ATPase is localized to the sinusoidal and lateral portions of the rat hepatocyte plasma membrane and is not detectable on the bile canaliculus where alkaline phosphatase is confined. This basolateral localization of Na+,K+-ATPase is similar to that found in epithelia where secretion is also directed across the apical membrane."}
{"id": "PMID:213447", "title": "Bihormonal regulation of the thyrotropin-releasing hormone receptor in mouse pituitary thyrotropic tumor cells in culture.", "content": "Receptors for thyrotropin-releasing hormone (TRH) are present on mouse pituitary thyrotropic tumor cells. Incubation of thyrotropes with 100 nM TRH or 4 nM L-triiodothyronine (T3) for 48 h decreased the number of TRH receptors to approximately equal to 50 and 20% of control, respectively. There was no effect on the equilibrium dissociation constant which was 3-5 nM. The depletion in the number of available TRH receptors was time- and dose-dependent. TRH, 100 nM, decreased the receptor number to 70% after 24 h, 50% after 48 h, and 45% of control after 72 h. T3, 4 nM, decreased the receptor number to 52% after 24 h, 20% after 48 h, and 17% of control after 72 h. After 48 h, half-maximal depletion occurred with 1-2 nM TRH and approximately equal to 0.15 nM T3. Incubation with 100 nM TRH and 4 nM T3 caused a significantly greater reduction in the receptor level than either hormone alone. The decrease in the receptor level was reversible within 72 h after removal of TRH, 100 nM, but was only partially reversed, from 20 to 40% of control, after removal of T3, 4 nM, after 120 h. By regulating the number of available TRH receptors on the thyrotrope. TRH and T3 interact to control thyrotropin release.", "contents": "Bihormonal regulation of the thyrotropin-releasing hormone receptor in mouse pituitary thyrotropic tumor cells in culture. Receptors for thyrotropin-releasing hormone (TRH) are present on mouse pituitary thyrotropic tumor cells. Incubation of thyrotropes with 100 nM TRH or 4 nM L-triiodothyronine (T3) for 48 h decreased the number of TRH receptors to approximately equal to 50 and 20% of control, respectively. There was no effect on the equilibrium dissociation constant which was 3-5 nM. The depletion in the number of available TRH receptors was time- and dose-dependent. TRH, 100 nM, decreased the receptor number to 70% after 24 h, 50% after 48 h, and 45% of control after 72 h. T3, 4 nM, decreased the receptor number to 52% after 24 h, 20% after 48 h, and 17% of control after 72 h. After 48 h, half-maximal depletion occurred with 1-2 nM TRH and approximately equal to 0.15 nM T3. Incubation with 100 nM TRH and 4 nM T3 caused a significantly greater reduction in the receptor level than either hormone alone. The decrease in the receptor level was reversible within 72 h after removal of TRH, 100 nM, but was only partially reversed, from 20 to 40% of control, after removal of T3, 4 nM, after 120 h. By regulating the number of available TRH receptors on the thyrotrope. TRH and T3 interact to control thyrotropin release."}
{"id": "PMID:213448", "title": "Activation in vitro of rheumatoid synovial collagenase from cell cultures.", "content": "Rheumatoid synovial cells dissociated from matrix and adherent to culture dishes released a latent form of collagenase into culture medium. Previous studies have shown that the latent enzyme does not complex with alpha2-macroglobulin and binds to fibrillar substrate. We now show that serum-free culture medium of the synovial cells contains an inhibitor of collagenase as well as latent enzyme; the two were separated on a column of acrylamide/agarose. Latent collagenase (estimated mol wt 45,000-49,000) was transformed by trypsin to active collagenase of approximately equal to mol wt 33,000. When mixed with inhibitor the active enzyme formed an inactive complex again with approximately equal to mol wt 45,000-49,000. The inhibitor(s) itself was found in one major peak of mol wt 33,000-35,000 and several minor peaks eluting with lower apparent molecular weight. Mersalyl, an organic mercurial compound, effectively activated latent collagenase producing an active enzyme with approximately equal to mol wt 33,000. Bacterial collagenase did not activate latent enzyme. We suggest that latent rheumatoid synovial collagenase, as it is harvested from synovial cells in culture, is an enzyme-inhibitor complex.", "contents": "Activation in vitro of rheumatoid synovial collagenase from cell cultures. Rheumatoid synovial cells dissociated from matrix and adherent to culture dishes released a latent form of collagenase into culture medium. Previous studies have shown that the latent enzyme does not complex with alpha2-macroglobulin and binds to fibrillar substrate. We now show that serum-free culture medium of the synovial cells contains an inhibitor of collagenase as well as latent enzyme; the two were separated on a column of acrylamide/agarose. Latent collagenase (estimated mol wt 45,000-49,000) was transformed by trypsin to active collagenase of approximately equal to mol wt 33,000. When mixed with inhibitor the active enzyme formed an inactive complex again with approximately equal to mol wt 45,000-49,000. The inhibitor(s) itself was found in one major peak of mol wt 33,000-35,000 and several minor peaks eluting with lower apparent molecular weight. Mersalyl, an organic mercurial compound, effectively activated latent collagenase producing an active enzyme with approximately equal to mol wt 33,000. Bacterial collagenase did not activate latent enzyme. We suggest that latent rheumatoid synovial collagenase, as it is harvested from synovial cells in culture, is an enzyme-inhibitor complex."}
{"id": "PMID:213449", "title": "Incomplete anaerobiosis as a cause of metronidazole 'resistance'.", "content": "Clostridium welchii, used as a control, was found to grow well in a microaerophilic jar used for campylobacters but appeared resistant to a metronidazole disc although the campylobacter was sensitive. Minimum inhibitory concentrations for six strains of Cl. welchii were up to 64-fold higher in these conditions than when grown anaerobically. Zones of inhibition with both Cl. welchii and Bacteroides fragilis varied with the amount of air admitted to anaerobic jars.", "contents": "Incomplete anaerobiosis as a cause of metronidazole 'resistance'. Clostridium welchii, used as a control, was found to grow well in a microaerophilic jar used for campylobacters but appeared resistant to a metronidazole disc although the campylobacter was sensitive. Minimum inhibitory concentrations for six strains of Cl. welchii were up to 64-fold higher in these conditions than when grown anaerobically. Zones of inhibition with both Cl. welchii and Bacteroides fragilis varied with the amount of air admitted to anaerobic jars."}
{"id": "PMID:213450", "title": "A comparison of complement fixation, indirect immunofluorescence for viral late antigens, and anti-complement immunofluorescence tests for the detection of cytomegalovirus specific serum antibodies.", "content": "It was shown that, on average, the titres of the sera obtained by both the anti-complement immunofluorescence (ACIF) and indirect immunofluorescence for viral late antigens (IFA-LA) procedures were approximately eight times higher than those obtained by complement fixation. There was no significant difference between the mean ACIF and IFA-LA titres, but the former method was preferred because it was not affected by non-specific staining. When 406 sera were screened for the presence or absence of antibodies, only five sera (1.2%) gave discordant results with the three tests. None of the tests could detect all of the sera that contained specific antibodies while each test detected over 98% of these sera. Thus, the increased sensitivity of the immunofluorescence procedures did not result in an appreciably increased rate of detection of cytomegalovirus seropositive sera.", "contents": "A comparison of complement fixation, indirect immunofluorescence for viral late antigens, and anti-complement immunofluorescence tests for the detection of cytomegalovirus specific serum antibodies. It was shown that, on average, the titres of the sera obtained by both the anti-complement immunofluorescence (ACIF) and indirect immunofluorescence for viral late antigens (IFA-LA) procedures were approximately eight times higher than those obtained by complement fixation. There was no significant difference between the mean ACIF and IFA-LA titres, but the former method was preferred because it was not affected by non-specific staining. When 406 sera were screened for the presence or absence of antibodies, only five sera (1.2%) gave discordant results with the three tests. None of the tests could detect all of the sera that contained specific antibodies while each test detected over 98% of these sera. Thus, the increased sensitivity of the immunofluorescence procedures did not result in an appreciably increased rate of detection of cytomegalovirus seropositive sera."}
{"id": "PMID:213451", "title": "Identification of thorium dioxide in human liver cells by electron microscopic x-ray microanalysis.", "content": "Thirty-two years after injection of thorium dioxide (Thorotrast) for diagnostic x-ray studies in a female patient deposits were found by light microscopy in the liver macrophages (Kupffer cells). They were shown by electron microscopy to be located inside secondary lysosomes, and by autoradiography and x-ray microanalysis they were identified as thorium.", "contents": "Identification of thorium dioxide in human liver cells by electron microscopic x-ray microanalysis. Thirty-two years after injection of thorium dioxide (Thorotrast) for diagnostic x-ray studies in a female patient deposits were found by light microscopy in the liver macrophages (Kupffer cells). They were shown by electron microscopy to be located inside secondary lysosomes, and by autoradiography and x-ray microanalysis they were identified as thorium."}
{"id": "PMID:213452", "title": "Multifocal histogenesis of a cystosarcoma phyllodes.", "content": "An unusual multifocal cystosarcoma phyllodes is reported. It presented as a small, circumscribed tumour mass, which was associated with two diffuse neoplastic lesions which arose sequentially in two geographically separate parts of the mammary disc. Microscopically the tumour appeared to have been enlarging by the formation of isolated satellite tumour nodules within the adjacent normal breast tissue, which represents a third, though rarer way in which a cystosarcoma phyllodes may enlarge.", "contents": "Multifocal histogenesis of a cystosarcoma phyllodes. An unusual multifocal cystosarcoma phyllodes is reported. It presented as a small, circumscribed tumour mass, which was associated with two diffuse neoplastic lesions which arose sequentially in two geographically separate parts of the mammary disc. Microscopically the tumour appeared to have been enlarging by the formation of isolated satellite tumour nodules within the adjacent normal breast tissue, which represents a third, though rarer way in which a cystosarcoma phyllodes may enlarge."}
{"id": "PMID:213456", "title": "Case report. Hypoglossal palsy: computed tomography demonstration of denervation hemiatrophy of the tongue associated with glomus jugulare tumor.", "content": "In a patient with left glomus jugulare tumor and left hypoglossal nerve palsy, computed tomography demonstrated focal lucency of the left half of the tongue. This was interpreted to represent postdenervation fibrosis and fatty replacement of the intrinsic and extrinsic lingual muscles supplied by the hypoglossal (XIIth cranial) nerve.", "contents": "Case report. Hypoglossal palsy: computed tomography demonstration of denervation hemiatrophy of the tongue associated with glomus jugulare tumor. In a patient with left glomus jugulare tumor and left hypoglossal nerve palsy, computed tomography demonstrated focal lucency of the left half of the tongue. This was interpreted to represent postdenervation fibrosis and fatty replacement of the intrinsic and extrinsic lingual muscles supplied by the hypoglossal (XIIth cranial) nerve."}
{"id": "PMID:213459", "title": "Consumer acceptability of day care after operations for hernia or varicose veins.", "content": "The opinions of patients and of caring persons (usually relatives) were sought in this trial of different methods of providing care for 360 patients after operations for hernia or varicose veins. Analysis of patients' opinions suggested that day care was the most acceptable of the three types of care examined. The reactions of caring persons did not reveal any major criticisms or disadvantages.", "contents": "Consumer acceptability of day care after operations for hernia or varicose veins. The opinions of patients and of caring persons (usually relatives) were sought in this trial of different methods of providing care for 360 patients after operations for hernia or varicose veins. Analysis of patients' opinions suggested that day care was the most acceptable of the three types of care examined. The reactions of caring persons did not reveal any major criticisms or disadvantages."}
{"id": "PMID:213460", "title": "Economic aspects of day care after operations for hernia or varicose veins.", "content": "In a trial of 360 patients with hernia or varicose veins, day care surgery provided an economic alternative to the provision of surgical aftercare either in the surgical wards of a district hospital or in a convalescent hospital. There was only slightly more work for general practitioners. Most of the additional work for the community services was carried out by district nurses, with an average contact time in the postoperative period of 325 minutes for day care patients, compared with 186 minutes and 204 minutes respectively for patients admitted for 48 hours to the surgical or convalescent wards. Day care produced estimated savings of 30 pounds compared with the costs of a 48-hour stay in the surgical wards, and savings of 22 pounds compared with a 48-hour stay in the convalescent wards.", "contents": "Economic aspects of day care after operations for hernia or varicose veins. In a trial of 360 patients with hernia or varicose veins, day care surgery provided an economic alternative to the provision of surgical aftercare either in the surgical wards of a district hospital or in a convalescent hospital. There was only slightly more work for general practitioners. Most of the additional work for the community services was carried out by district nurses, with an average contact time in the postoperative period of 325 minutes for day care patients, compared with 186 minutes and 204 minutes respectively for patients admitted for 48 hours to the surgical or convalescent wards. Day care produced estimated savings of 30 pounds compared with the costs of a 48-hour stay in the surgical wards, and savings of 22 pounds compared with a 48-hour stay in the convalescent wards."}
{"id": "PMID:213486", "title": "On the quantitation of SV40 virus by plaque assay and immunoperoxidase technique.", "content": "Procedures are described for the quantitation of SV40 virus infectivity by plaque formation within 7 days and T antigen assay by the sensitive and economical indirect immunoperoxidase technique.", "contents": "On the quantitation of SV40 virus by plaque assay and immunoperoxidase technique. Procedures are described for the quantitation of SV40 virus infectivity by plaque formation within 7 days and T antigen assay by the sensitive and economical indirect immunoperoxidase technique."}
{"id": "PMID:213487", "title": "Quantitative histological studies on the lateral geniculate nucleus in the cat. IV. Numerical aspects of the transfer from restinal fibers to cortical relay.", "content": "The numerical data, gained both from the quantitative histology and Golgi stained material was completed with those of optic fibers. The number of X and Y fibers was estimated on the basis of our results, on the data of literature and from the ratio of the large and medium size relay neurons. The crossed and uncrossed fibers were counted and compared with the number of relay neurons in layer A and A1. Knowing the different numerical and metrical counts of neuronal elements in LGN of cat some calculations were carried out on the overlaping of optic fiber arborizations, on the intersections of dendritic ramification points of relay neurons and on the spatial arrangement of both the optic terminals and the relay neurons. The comparison of the neumerical data on relay neurons and optic fibers and their relations were the basic factors of considerations on divergence and convergence of retinal input.", "contents": "Quantitative histological studies on the lateral geniculate nucleus in the cat. IV. Numerical aspects of the transfer from restinal fibers to cortical relay. The numerical data, gained both from the quantitative histology and Golgi stained material was completed with those of optic fibers. The number of X and Y fibers was estimated on the basis of our results, on the data of literature and from the ratio of the large and medium size relay neurons. The crossed and uncrossed fibers were counted and compared with the number of relay neurons in layer A and A1. Knowing the different numerical and metrical counts of neuronal elements in LGN of cat some calculations were carried out on the overlaping of optic fiber arborizations, on the intersections of dendritic ramification points of relay neurons and on the spatial arrangement of both the optic terminals and the relay neurons. The comparison of the neumerical data on relay neurons and optic fibers and their relations were the basic factors of considerations on divergence and convergence of retinal input."}
{"id": "PMID:213489", "title": "Differences in activation of human and guinea pig complement by retroviruses.", "content": "C type murine leukemia viruses (retroviruses) have been shown previously to possess a receptor for human C1 that activated human but not guinea pig complement. In the present study we provide evidence that the viral receptor also binds guinea pig C1 but that such binding does not lead to activation. However, incorporation of human C1s into guinea pig C1 to form a C1 hybrid results in activation of that hybrid and in viral lysis. In contrast, incorporation of guinea pig C1s into human C1 abolishes activation by the virus. These results demonstrate that C1s governs the activation of C1 of the viral receptor.", "contents": "Differences in activation of human and guinea pig complement by retroviruses. C type murine leukemia viruses (retroviruses) have been shown previously to possess a receptor for human C1 that activated human but not guinea pig complement. In the present study we provide evidence that the viral receptor also binds guinea pig C1 but that such binding does not lead to activation. However, incorporation of human C1s into guinea pig C1 to form a C1 hybrid results in activation of that hybrid and in viral lysis. In contrast, incorporation of guinea pig C1s into human C1 abolishes activation by the virus. These results demonstrate that C1s governs the activation of C1 of the viral receptor."}
{"id": "PMID:213490", "title": "In vitro immune response of human peripheral lymphocytes. III. Effect of anti-mu or anti-delta antibody on PWM-induced increase of cyclic nucleotides in human B lymphocytes.", "content": "Stimulation of human peripheral blood lymphocytes (PBL) with pokeweed mitogen (PWM) induced consistent increases of intracellular levels of cyclic AMP and cyclic GMP within 15 min. Increases of cyclic AMP were observed in both B and T lymphocyte populations, but increase of cyclic GMP was observed only in the B lymphocyte population. The addition of anti-mu antibody to B cells abolished PWM-induced increase of cyclic GMP without any effect on cyclic AMP response. Anti-delta antibody did not show any inhibitory or stimulatory effect on PWM-induced increase of cyclic GMP or cyclic AMP. Pretreatment of B cells with anti-mu antibody at 37 degrees C for 1 hr inhibited PWM-induced increase of cyclic GMP, whereas pretreatment with anti-mu antibody at 4 degrees C did not show any inhibitory effect on PWM-induced increase of cyclic GMP. The effect of anti-mu-pretreatment was reversible and pretreated cells were recovered from the inhibitory effect of anti-mu antibody after 36 hr culture.", "contents": "In vitro immune response of human peripheral lymphocytes. III. Effect of anti-mu or anti-delta antibody on PWM-induced increase of cyclic nucleotides in human B lymphocytes. Stimulation of human peripheral blood lymphocytes (PBL) with pokeweed mitogen (PWM) induced consistent increases of intracellular levels of cyclic AMP and cyclic GMP within 15 min. Increases of cyclic AMP were observed in both B and T lymphocyte populations, but increase of cyclic GMP was observed only in the B lymphocyte population. The addition of anti-mu antibody to B cells abolished PWM-induced increase of cyclic GMP without any effect on cyclic AMP response. Anti-delta antibody did not show any inhibitory or stimulatory effect on PWM-induced increase of cyclic GMP or cyclic AMP. Pretreatment of B cells with anti-mu antibody at 37 degrees C for 1 hr inhibited PWM-induced increase of cyclic GMP, whereas pretreatment with anti-mu antibody at 4 degrees C did not show any inhibitory effect on PWM-induced increase of cyclic GMP. The effect of anti-mu-pretreatment was reversible and pretreated cells were recovered from the inhibitory effect of anti-mu antibody after 36 hr culture."}
{"id": "PMID:213491", "title": "Functional differentiation of B lymphocytes in agammaglobulinemia. III. Characterization of spontaneous suppressor cell activity.", "content": "The addition of fresh peripheral blood mononuclear cells (PBL) from four of seven patients with agammaglobulinemia to generated hemolytic plaque-forming cells (PFC) resulted in a dose-dependent suppression of PFC. This spontaneous suppressor cell activity (SSA) was restricted to the four patients who could generate a PFC response in vitro. SSA was mediated by a small subset of E-rosetting T lymphocytes characterized by theophylline-sensitive E-receptors and surface receptors for Fc-IgG. The effects of SSA were temperature dependent and reversible, and pokeweed mitogen could prevent the rapid decline of SSA observed during culture. Augmentation of SSA was achieved by agents known to increase intracellular levels of cyclic AMP, whereas lithium chloride abrogated SSA, including the drug-induced effects. Cells mediating SSA may play a role in preventing the normal transition of pre-B cells to B cells in patients with agammaglobulinemia without B lymphocytes.", "contents": "Functional differentiation of B lymphocytes in agammaglobulinemia. III. Characterization of spontaneous suppressor cell activity. The addition of fresh peripheral blood mononuclear cells (PBL) from four of seven patients with agammaglobulinemia to generated hemolytic plaque-forming cells (PFC) resulted in a dose-dependent suppression of PFC. This spontaneous suppressor cell activity (SSA) was restricted to the four patients who could generate a PFC response in vitro. SSA was mediated by a small subset of E-rosetting T lymphocytes characterized by theophylline-sensitive E-receptors and surface receptors for Fc-IgG. The effects of SSA were temperature dependent and reversible, and pokeweed mitogen could prevent the rapid decline of SSA observed during culture. Augmentation of SSA was achieved by agents known to increase intracellular levels of cyclic AMP, whereas lithium chloride abrogated SSA, including the drug-induced effects. Cells mediating SSA may play a role in preventing the normal transition of pre-B cells to B cells in patients with agammaglobulinemia without B lymphocytes."}
{"id": "PMID:213494", "title": "Enhancement of neutrophil chemotaxis and alteration of levels of cellular cyclic nucleotides by levamisole.", "content": "Levamisole, an antihelminthic agent reported to enhance nonspecifically various parameters of the immune response, was examined for its effect on chemotaxis of human neutrophils and on levels of cellular cyclic nucleotides. This agent was found, in most instances, to enhance chemotactic responses of neutrophils to a bacterial chemotactic factor derived from Escherichia coli. At similar concentrations, levamisole produced increases in levels of guanosine 3':5'-cyclic phosphate in neutrophils. In contrast, a decrease in concentrations of adenosine 3':5'-cyclic phosphate was observed when neutrophils were incubated with levamisole. Neutrophil chemotaxis, with and without the addition of levamisole, was assessed in 10 patients with recurrent infections. The illnesses of these patients included Job's syndrome, Wiskott-Aldrich syndrome, eczema with an increased level of IgE and recurrent abscesses, chronic mucocutaneous candidiasis, and diabetes mellitus. Levamisole significantly enhanced chemotaxis of polymorphonuclear leukocytes from these patients. Levamisole appears to have a profound effect on chemotactic responses of neutrophils which probably results from alterations in cellular cyclic nucleotide levels. Levamisole may prove to be useful therapeutically in certain patients with defective neutrophil chemotaxis.", "contents": "Enhancement of neutrophil chemotaxis and alteration of levels of cellular cyclic nucleotides by levamisole. Levamisole, an antihelminthic agent reported to enhance nonspecifically various parameters of the immune response, was examined for its effect on chemotaxis of human neutrophils and on levels of cellular cyclic nucleotides. This agent was found, in most instances, to enhance chemotactic responses of neutrophils to a bacterial chemotactic factor derived from Escherichia coli. At similar concentrations, levamisole produced increases in levels of guanosine 3':5'-cyclic phosphate in neutrophils. In contrast, a decrease in concentrations of adenosine 3':5'-cyclic phosphate was observed when neutrophils were incubated with levamisole. Neutrophil chemotaxis, with and without the addition of levamisole, was assessed in 10 patients with recurrent infections. The illnesses of these patients included Job's syndrome, Wiskott-Aldrich syndrome, eczema with an increased level of IgE and recurrent abscesses, chronic mucocutaneous candidiasis, and diabetes mellitus. Levamisole significantly enhanced chemotaxis of polymorphonuclear leukocytes from these patients. Levamisole appears to have a profound effect on chemotactic responses of neutrophils which probably results from alterations in cellular cyclic nucleotide levels. Levamisole may prove to be useful therapeutically in certain patients with defective neutrophil chemotaxis."}
{"id": "PMID:213495", "title": "Diagnosis and etiology of nongonococcal urethritis.", "content": "The observation of more than four polymorphonuclear cells (PMN) per high-power field (hpf) in gram-stained smears of urethral secretions was found to differentiate patients with urethritis from patients without urethritis. A urethral discharge was present in 78% of patients with nongonococcal urethritis (NGU). Dysuria without demonstrable urethral discharge and with fewer than four PMN/hpf did not appear to fit into the NGU spectrum. NGU is now defined to include men who have negative urethral cultures for Neisseria gonorrhoeae with a urethral discharge and/or more than four PMN/hpf in their urethral smears. The findings of more than four PMN/hpf in the urethral smears of 22%of asymptomatic sexually active men with more than one sexual partner (polygamous controls) suggests that asymptomatic NGU is not uncommon. Chlamydia trachomatis was isolated significantly more frequently from the NGU study group than from the control group (P less than 0.001). This study adds Corynebacterium vaginale (Haemophilus vaginalis), group B streptococci, and yeasts to the list of sexually transmitted microorganisms that are not etiologic determinants of NGU.", "contents": "Diagnosis and etiology of nongonococcal urethritis. The observation of more than four polymorphonuclear cells (PMN) per high-power field (hpf) in gram-stained smears of urethral secretions was found to differentiate patients with urethritis from patients without urethritis. A urethral discharge was present in 78% of patients with nongonococcal urethritis (NGU). Dysuria without demonstrable urethral discharge and with fewer than four PMN/hpf did not appear to fit into the NGU spectrum. NGU is now defined to include men who have negative urethral cultures for Neisseria gonorrhoeae with a urethral discharge and/or more than four PMN/hpf in their urethral smears. The findings of more than four PMN/hpf in the urethral smears of 22%of asymptomatic sexually active men with more than one sexual partner (polygamous controls) suggests that asymptomatic NGU is not uncommon. Chlamydia trachomatis was isolated significantly more frequently from the NGU study group than from the control group (P less than 0.001). This study adds Corynebacterium vaginale (Haemophilus vaginalis), group B streptococci, and yeasts to the list of sexually transmitted microorganisms that are not etiologic determinants of NGU."}
{"id": "PMID:213496", "title": "Restriction endonuclease fingerprinting of herpes simplex virus DNA: a novel epidemiological tool applied to a nosocomial outbreak.", "content": "In a blind study, 14 isolates of herpes simplex virus type 1 (HSV-1) that included nine isolates from a temporal cluster of HSV infections in a hospital Pediatric Intensive Care Unit and five unrelated isolates were analyzed by digestion of their DNA with four restriction endonucleases. These enzymes (HsuI, BglII, EcoRI, and HpaI) cleave the DNA in about 52 sites. To date, at least 16 sites have been found to be variable in the sense that they may be present or absent independently of any other cleavage site. This characteristic is stable, and no change was observed on serial propagation of the strains in culture or following repeated isolation, as long as 12 years apart, from humans. Analyses of the isolates readily discriminated between those belonging to the temporal cluster of hospital infections and the unrelated strains. They also showed that there were two independent introductions of HSV-1 into the Pediatric Intensive Care Unit resulting in two clusters of epidemiologically related infections. This type of analysis has the potential of becoming a powerful tool for tracing the spread of HSV-1 and very likely of other herpesviruses in the human population.", "contents": "Restriction endonuclease fingerprinting of herpes simplex virus DNA: a novel epidemiological tool applied to a nosocomial outbreak. In a blind study, 14 isolates of herpes simplex virus type 1 (HSV-1) that included nine isolates from a temporal cluster of HSV infections in a hospital Pediatric Intensive Care Unit and five unrelated isolates were analyzed by digestion of their DNA with four restriction endonucleases. These enzymes (HsuI, BglII, EcoRI, and HpaI) cleave the DNA in about 52 sites. To date, at least 16 sites have been found to be variable in the sense that they may be present or absent independently of any other cleavage site. This characteristic is stable, and no change was observed on serial propagation of the strains in culture or following repeated isolation, as long as 12 years apart, from humans. Analyses of the isolates readily discriminated between those belonging to the temporal cluster of hospital infections and the unrelated strains. They also showed that there were two independent introductions of HSV-1 into the Pediatric Intensive Care Unit resulting in two clusters of epidemiologically related infections. This type of analysis has the potential of becoming a powerful tool for tracing the spread of HSV-1 and very likely of other herpesviruses in the human population."}
{"id": "PMID:213497", "title": "Inhibition of mitogen- and antigen-induced lymphocyte blastogenesis by herpes simplex virus.", "content": "Lymphocytes were separated from peripheral blood of adult human donors by Ficoll-Hypaque gradient centrifugation and cultured in the presence of nonspecific mitogens (phytohemagglutinin[PHA] and concanavalin A) or specific microbial anatigens (herpes simplex virus [HSV], mumps virus, streptococcal enzymes, and Candida albicans). Exposure of lymphocyte cultures to infectious HSV resulted in almost complete inhibition of blastogenesis ([3/H]thymidine uptake) induced by each of the mitogens and antigens, a finding which suggests that a common mechanism may underlie the inhibitory effect. Several characteristics of the effect of virus on blastogenesis were noted: (1) virus inactivated by heat or ultraviolet irradiation was ineffective; (2) inhibition (is greater than 90%) was greatest in cultures exposed to HSV on or before the addition of PHA; (3) lymphocyte preparations washed free of HSV continued to be refractory to stimulation, an observation indicating that the presence of unabsorbed virions or viral products was not essential; and (4) inhibition was independent of the cell donor's state of humoral immunity to HSV.", "contents": "Inhibition of mitogen- and antigen-induced lymphocyte blastogenesis by herpes simplex virus. Lymphocytes were separated from peripheral blood of adult human donors by Ficoll-Hypaque gradient centrifugation and cultured in the presence of nonspecific mitogens (phytohemagglutinin[PHA] and concanavalin A) or specific microbial anatigens (herpes simplex virus [HSV], mumps virus, streptococcal enzymes, and Candida albicans). Exposure of lymphocyte cultures to infectious HSV resulted in almost complete inhibition of blastogenesis ([3/H]thymidine uptake) induced by each of the mitogens and antigens, a finding which suggests that a common mechanism may underlie the inhibitory effect. Several characteristics of the effect of virus on blastogenesis were noted: (1) virus inactivated by heat or ultraviolet irradiation was ineffective; (2) inhibition (is greater than 90%) was greatest in cultures exposed to HSV on or before the addition of PHA; (3) lymphocyte preparations washed free of HSV continued to be refractory to stimulation, an observation indicating that the presence of unabsorbed virions or viral products was not essential; and (4) inhibition was independent of the cell donor's state of humoral immunity to HSV."}
{"id": "PMID:213498", "title": "Effect of CP-20,961, an interferon inducer, on upper respiratory tract infections due to rhinovirus type 21 in volunteers.", "content": "Topically administered CP-20,961 is known to stimulate nasal interferon. Studies in volunteers given the drug prior to challenge with rhinovirus have yielded both fairly good results and only fair or poor results. This study was undertaken in an attempt to settle the differences between the results of these trials and to evaluate the possible effectiveness of CP-20, 961 when given after virus challenge. Sixty volunteers were randomly divided into four groups. One group received placebo, the second received the drug on the day before and the day of challenge, the third was given the drug for two days beginning 24 hr after challenge, and the fourth received the drug for two days beginning 48 hr after challenge. The average number and severity of symptoms in the group that received CP-20,961 prior to challenge were about half of those in the control group. There was no decrease, however, in the number and severity of symptoms in the groups that received the drug after challenge.", "contents": "Effect of CP-20,961, an interferon inducer, on upper respiratory tract infections due to rhinovirus type 21 in volunteers. Topically administered CP-20,961 is known to stimulate nasal interferon. Studies in volunteers given the drug prior to challenge with rhinovirus have yielded both fairly good results and only fair or poor results. This study was undertaken in an attempt to settle the differences between the results of these trials and to evaluate the possible effectiveness of CP-20, 961 when given after virus challenge. Sixty volunteers were randomly divided into four groups. One group received placebo, the second received the drug on the day before and the day of challenge, the third was given the drug for two days beginning 24 hr after challenge, and the fourth received the drug for two days beginning 48 hr after challenge. The average number and severity of symptoms in the group that received CP-20,961 prior to challenge were about half of those in the control group. There was no decrease, however, in the number and severity of symptoms in the groups that received the drug after challenge."}
{"id": "PMID:213499", "title": "Sensitivity of the virus isolation and immunofluorescent staining methods in diagnosis of infections with herpes simplex virus.", "content": "Tissues from marmoset monkeys infected with herpes simplex virus (HSV, Herpes-virus hominis) were utilized to evaluate the relative sensitivity and limitation of the virus isolation technique and the immunofluorescent (fluorescent antibody or FA) staining method for diagnosis of HSV infection. HSV encephalitis and/or disseminated infection in marmosets were established by intracerebral, intramuscular, or intravenous inoculation of the virus. Brain tissues, liver, spleen, kidney, adrenal gland, lymph node, and lung were harvested and prepared for the virus isolation procedure in tissue culture and for direct FA staining. Data from six marmosets infected with HSV type 1 and two infected with type 2 indicated that the virus isolation method was more sensitive and reliable than the FA staining technique. False-negative results by FA staining were found in two situations: (1) presence of focal lesions that were missed by the frozen sections, and (2) presence of low concentrations of virus in tissue (is less than or equal to 3.5 log10 50% tissue culture infective doses/g). FA staining provides a rapid method for detection of viral antigens, but isolation of virus in tissue culture is required for a conclusive diagnosis of active infection.", "contents": "Sensitivity of the virus isolation and immunofluorescent staining methods in diagnosis of infections with herpes simplex virus. Tissues from marmoset monkeys infected with herpes simplex virus (HSV, Herpes-virus hominis) were utilized to evaluate the relative sensitivity and limitation of the virus isolation technique and the immunofluorescent (fluorescent antibody or FA) staining method for diagnosis of HSV infection. HSV encephalitis and/or disseminated infection in marmosets were established by intracerebral, intramuscular, or intravenous inoculation of the virus. Brain tissues, liver, spleen, kidney, adrenal gland, lymph node, and lung were harvested and prepared for the virus isolation procedure in tissue culture and for direct FA staining. Data from six marmosets infected with HSV type 1 and two infected with type 2 indicated that the virus isolation method was more sensitive and reliable than the FA staining technique. False-negative results by FA staining were found in two situations: (1) presence of focal lesions that were missed by the frozen sections, and (2) presence of low concentrations of virus in tissue (is less than or equal to 3.5 log10 50% tissue culture infective doses/g). FA staining provides a rapid method for detection of viral antigens, but isolation of virus in tissue culture is required for a conclusive diagnosis of active infection."}
{"id": "PMID:213500", "title": "Cell-mediated immunity to murine cytomegalovirus.", "content": "Cell-mediated immunity to murine cytomegalovirus (CMV) was tested by an in vitro lymphocyte proliferation assay. CMV antigen was prepared from infected mouse embryo fibroblasts by ultracentrifugation. Control antigen was prepared in a similar fashion from uninfected fibroblasts. Splenic lymphocytes from CMV-infected mice underwent significant proliferation when incubated with CMV antigen. Lymphocytes from uninfected mice did not proliferate when incubated in vitro with CMV antigen. The proliferation was shown to be specific, since lymphocytes from CMV-infected mice did not proliferate when incubated with control antigen or an indifferent (encephalomyocarditis) viral antigen. Lymphocyte proliferation was directly related to the number of lymphocytes in each culture and to the amount of viral antigen. However, at higher numbers of cells and with large amounts of viral antigen, the backgrounds increased, and the standard errors were larger. The optimal incubation time was eight days. Lymphocyte proliferation reached a maximum 15 days after CMV infection but was still significantly elevated above background 60 days later. This type of lymphocyte proliferation test with human lymphocytes and human CMV antigen can be used to study clinical questions regarding cell-mediated immunity to CMV in immunosuppressed patients, in children with congenital CMV, and in transplant patients after vaccination with attenuated CMV.", "contents": "Cell-mediated immunity to murine cytomegalovirus. Cell-mediated immunity to murine cytomegalovirus (CMV) was tested by an in vitro lymphocyte proliferation assay. CMV antigen was prepared from infected mouse embryo fibroblasts by ultracentrifugation. Control antigen was prepared in a similar fashion from uninfected fibroblasts. Splenic lymphocytes from CMV-infected mice underwent significant proliferation when incubated with CMV antigen. Lymphocytes from uninfected mice did not proliferate when incubated in vitro with CMV antigen. The proliferation was shown to be specific, since lymphocytes from CMV-infected mice did not proliferate when incubated with control antigen or an indifferent (encephalomyocarditis) viral antigen. Lymphocyte proliferation was directly related to the number of lymphocytes in each culture and to the amount of viral antigen. However, at higher numbers of cells and with large amounts of viral antigen, the backgrounds increased, and the standard errors were larger. The optimal incubation time was eight days. Lymphocyte proliferation reached a maximum 15 days after CMV infection but was still significantly elevated above background 60 days later. This type of lymphocyte proliferation test with human lymphocytes and human CMV antigen can be used to study clinical questions regarding cell-mediated immunity to CMV in immunosuppressed patients, in children with congenital CMV, and in transplant patients after vaccination with attenuated CMV."}
{"id": "PMID:213501", "title": "A long-term survey of rotavirus infection in Japanese children with acute gastroenteritis.", "content": "Human rotavirus was detected by electron microscopic examination of the stools of 320 (63%) of 506 infants and young children hospitalized with acute gastroenteritis between December 1974 and March 1977. Serologic responses to infection with the rotavirus were revealed by the complement-fixation test in 130 (70%) of 185 patients examined. During the study period three epidemics of human rotavirus infection occurred during the winter months. The peak incidences occurred in January 1975 (88% of patients positive by serologic analysis or electron microscopy of stools), January 1976 (92%), and February 1977 (96%). Rotavirus was detected in the stools of 288 (79%) of 365 patients tested during the cooler months (December to March) and 35 (25%) of 141 during the rest of the year. In the summer (June to August), rotavirus infection occurred rarely. The frequency of human rotavirus infection was highest among patients aged six to 11 months. These results indicate that human rotavirus can be regarded as a major etiologic agent of acute gastroenteritis in infants and young children, of which wintertime epidemics are common in Japan.", "contents": "A long-term survey of rotavirus infection in Japanese children with acute gastroenteritis. Human rotavirus was detected by electron microscopic examination of the stools of 320 (63%) of 506 infants and young children hospitalized with acute gastroenteritis between December 1974 and March 1977. Serologic responses to infection with the rotavirus were revealed by the complement-fixation test in 130 (70%) of 185 patients examined. During the study period three epidemics of human rotavirus infection occurred during the winter months. The peak incidences occurred in January 1975 (88% of patients positive by serologic analysis or electron microscopy of stools), January 1976 (92%), and February 1977 (96%). Rotavirus was detected in the stools of 288 (79%) of 365 patients tested during the cooler months (December to March) and 35 (25%) of 141 during the rest of the year. In the summer (June to August), rotavirus infection occurred rarely. The frequency of human rotavirus infection was highest among patients aged six to 11 months. These results indicate that human rotavirus can be regarded as a major etiologic agent of acute gastroenteritis in infants and young children, of which wintertime epidemics are common in Japan."}
{"id": "PMID:213502", "title": "Resistance of visna virus to interferon.", "content": "Visna is a slow infection of sheep caused by a retrovirus. The persistence of virus despite the immune response of the host is best explained by restricted genetic expression of the virus and consequently prolonged periods of residence inside cells. The purpose of this investigation was to determine whether the restriction in genetic expression of visna virus is mediated by interferon. Sheep interferon induced by polyriboinosinic-polyribocytidylic acid in fetal lambs inhibited the growth of herpes simplex virus, vesicular stomatitis virus, and vaccinia virus, but even highly concentrated interferon did not affect the replication of visna virus in sheep choroid plexus cells. The same results were obtained whether the effects of interferon were assessed in single of multiple cycles of growth and when interferon was added at later times in the growth cycle of the virus. This unusual resistance of visna virus to interferon suggests that restriction of viral expression by the host is probably not mediated in this way.", "contents": "Resistance of visna virus to interferon. Visna is a slow infection of sheep caused by a retrovirus. The persistence of virus despite the immune response of the host is best explained by restricted genetic expression of the virus and consequently prolonged periods of residence inside cells. The purpose of this investigation was to determine whether the restriction in genetic expression of visna virus is mediated by interferon. Sheep interferon induced by polyriboinosinic-polyribocytidylic acid in fetal lambs inhibited the growth of herpes simplex virus, vesicular stomatitis virus, and vaccinia virus, but even highly concentrated interferon did not affect the replication of visna virus in sheep choroid plexus cells. The same results were obtained whether the effects of interferon were assessed in single of multiple cycles of growth and when interferon was added at later times in the growth cycle of the virus. This unusual resistance of visna virus to interferon suggests that restriction of viral expression by the host is probably not mediated in this way."}
{"id": "PMID:213503", "title": "Experimental congenital infection with cytomegalovirus: a guinea pig model.", "content": "An animal model permitting study of congenital infections with cytomegalovirus (CMV) has been developed in guinea pigs. Fifteen Hartley strain guinea pigs in the latter half of pregnancy were inoculated intraperitoneally with 10(5.5) 50% tissue culture infective doses of guinea pig CMV. Forty percent of infected mothers delivered litters containing at least one infected newborn, as defined by a positive culture of lung, spleen, or brain. All tissues were cultured by an explant technique. The three mothers who had no detectable complement-fixing antibody to CMV prior to experimental infection delivered infected litters, whereas three of 12 immune mothers delivered infected litters (P less than 0.01). A low-passage, tissue culture-adapted virus produced neonatal infection as frequently as did salivary gland-passaged virus. No congenital abnormalities were found in any of the seven infected newborns. CMV was isolated from lung, spleen, or brain in the four newborns of nonimmune mothers; CMV was isolated from lung only in the three newborns of immune mothers. These preliminary experiments demonstrate that the guinea pig is a suitable animal for further study of maternal-fetal CMV infections.", "contents": "Experimental congenital infection with cytomegalovirus: a guinea pig model. An animal model permitting study of congenital infections with cytomegalovirus (CMV) has been developed in guinea pigs. Fifteen Hartley strain guinea pigs in the latter half of pregnancy were inoculated intraperitoneally with 10(5.5) 50% tissue culture infective doses of guinea pig CMV. Forty percent of infected mothers delivered litters containing at least one infected newborn, as defined by a positive culture of lung, spleen, or brain. All tissues were cultured by an explant technique. The three mothers who had no detectable complement-fixing antibody to CMV prior to experimental infection delivered infected litters, whereas three of 12 immune mothers delivered infected litters (P less than 0.01). A low-passage, tissue culture-adapted virus produced neonatal infection as frequently as did salivary gland-passaged virus. No congenital abnormalities were found in any of the seven infected newborns. CMV was isolated from lung, spleen, or brain in the four newborns of nonimmune mothers; CMV was isolated from lung only in the three newborns of immune mothers. These preliminary experiments demonstrate that the guinea pig is a suitable animal for further study of maternal-fetal CMV infections."}
{"id": "PMID:213504", "title": "Isolation of viruses from cultures of bovine endometrial cells.", "content": "Endometrial cells from the uteri of pregnant and nonpregnant cattle were cultured. The presence of one or both of two viruses, noncytopathic mucosal disease virus and bovine syncytial virus, was demonstrated in seven of 19 endometria investigated. It was necessary to subculture the cells an average of four times to detect the viral infections. Difficulties were encountered in producing endometrial cell cultures from cows at term or near the end of term and also from older animals. The infections detected may be significant because both of the viruses isolated are capable of infecting the bovine fetus in utero and mucosal disease virus has been associated with bovine fetal diseases.", "contents": "Isolation of viruses from cultures of bovine endometrial cells. Endometrial cells from the uteri of pregnant and nonpregnant cattle were cultured. The presence of one or both of two viruses, noncytopathic mucosal disease virus and bovine syncytial virus, was demonstrated in seven of 19 endometria investigated. It was necessary to subculture the cells an average of four times to detect the viral infections. Difficulties were encountered in producing endometrial cell cultures from cows at term or near the end of term and also from older animals. The infections detected may be significant because both of the viruses isolated are capable of infecting the bovine fetus in utero and mucosal disease virus has been associated with bovine fetal diseases."}
{"id": "PMID:213505", "title": "Seroconversion against Epstein-Barr virus in two nonhuman primate species infected by the oropharyngeal route.", "content": "Transforming Epstein-Barr virus (EBV) was inoculated into eight squirrel monkeys (Saimiri sciureus) by spraying of viral concentrates into the nose and throat. Virus was inoculated into three marmosets (two Saguinus oedipus and one Calithrix jacchus jacchus) by direct injection into nasopharyngeal tissue. Two of these squirrel monkeys seroconverted after repeated inoculation as determined by the presence of EBV-specific antibodies to early antigen and viral capsid antigen. One squirrel monkey had antibody to EBV nuclear antigen only. One S. oedipus marmoset also seroconverted. None of the animals developed disease. The results show that seroconversion can be accomplished in squirrel monkeys after spraying of EBV into the nasopharynx, and in marmosets by direct inoculation of the virus into nasopharyngeal tissue.", "contents": "Seroconversion against Epstein-Barr virus in two nonhuman primate species infected by the oropharyngeal route. Transforming Epstein-Barr virus (EBV) was inoculated into eight squirrel monkeys (Saimiri sciureus) by spraying of viral concentrates into the nose and throat. Virus was inoculated into three marmosets (two Saguinus oedipus and one Calithrix jacchus jacchus) by direct injection into nasopharyngeal tissue. Two of these squirrel monkeys seroconverted after repeated inoculation as determined by the presence of EBV-specific antibodies to early antigen and viral capsid antigen. One squirrel monkey had antibody to EBV nuclear antigen only. One S. oedipus marmoset also seroconverted. None of the animals developed disease. The results show that seroconversion can be accomplished in squirrel monkeys after spraying of EBV into the nasopharynx, and in marmosets by direct inoculation of the virus into nasopharyngeal tissue."}
{"id": "PMID:213506", "title": "Comparison of myeloperoxidase activity in leukocytes from normal subjects and patients with chronic granulomatous disease.", "content": "A study was undertaken to compare myeloperoxidase (MPO) activity in leukocytes from normal subjects and those with chronic granulomatous disease (CGD) and to eliminate further consideration of MPO as the oxidase responsible for the post-phagocytic respiratory burst and subsequent oxidase microbicidal sequence lacking in leukocytes from patients with CGD. With use of granule fractions isolated from a number of samples, MPO activity in several MPO-mediated biochemical systems (peroxidase assays, protein iodination, and amino acid decarboxylation) was measured. No difference was demonstrated between granule fraction preparations from normal subjects and those with CGD. These data show that MPO activity is normal in CGD leukocytes and are inconsistent with a role for MPO in initiating the post-phagocytic respiratory burst.", "contents": "Comparison of myeloperoxidase activity in leukocytes from normal subjects and patients with chronic granulomatous disease. A study was undertaken to compare myeloperoxidase (MPO) activity in leukocytes from normal subjects and those with chronic granulomatous disease (CGD) and to eliminate further consideration of MPO as the oxidase responsible for the post-phagocytic respiratory burst and subsequent oxidase microbicidal sequence lacking in leukocytes from patients with CGD. With use of granule fractions isolated from a number of samples, MPO activity in several MPO-mediated biochemical systems (peroxidase assays, protein iodination, and amino acid decarboxylation) was measured. No difference was demonstrated between granule fraction preparations from normal subjects and those with CGD. These data show that MPO activity is normal in CGD leukocytes and are inconsistent with a role for MPO in initiating the post-phagocytic respiratory burst."}
{"id": "PMID:213510", "title": "Weakness, neuropathy, and coma following total parenteral nutrition in underfed or starved rats: relationship to blood hyperosmolarity and brain water loss.", "content": "The continuous infusion of a concentrated, high-caloric glucose solution intravenously into underfed or 3-day-starved rats at a rate of 390 kcal/kg/day results in hypophosphatemia, muscular weakness, neuropathy, lethargy, occasional convulsions, and eventual coma and death. This sequence of events is not observed in similarly infused normal rats. It is a model of a fatal parenteral nutrition syndrome which occurs in undernourished patients. Rats in coma had an eightfold increase in the blood glucose level, a 1.6-fold increase in serum osmolarity, a 16% to 20( decrease in brain water content, and normal blood ketones. A lag phase of at least 8 hr and often 12 to 24 hr occurred following the start of the hyperosmotic glucose infusion before the blood glucose began to accumulate progressively and the syndrome developed. The onset of the syndrome could be prevented by the administration of large amounts of insulin required to keep the blood sugar from exceeding 250 mg/dl. Thus the rat model of the fatal hyperalimentation syndrome is a form of hyperglycemic, hyperosmolar, nonketotic coma caused by brain dehydration.", "contents": "Weakness, neuropathy, and coma following total parenteral nutrition in underfed or starved rats: relationship to blood hyperosmolarity and brain water loss. The continuous infusion of a concentrated, high-caloric glucose solution intravenously into underfed or 3-day-starved rats at a rate of 390 kcal/kg/day results in hypophosphatemia, muscular weakness, neuropathy, lethargy, occasional convulsions, and eventual coma and death. This sequence of events is not observed in similarly infused normal rats. It is a model of a fatal parenteral nutrition syndrome which occurs in undernourished patients. Rats in coma had an eightfold increase in the blood glucose level, a 1.6-fold increase in serum osmolarity, a 16% to 20( decrease in brain water content, and normal blood ketones. A lag phase of at least 8 hr and often 12 to 24 hr occurred following the start of the hyperosmotic glucose infusion before the blood glucose began to accumulate progressively and the syndrome developed. The onset of the syndrome could be prevented by the administration of large amounts of insulin required to keep the blood sugar from exceeding 250 mg/dl. Thus the rat model of the fatal hyperalimentation syndrome is a form of hyperglycemic, hyperosmolar, nonketotic coma caused by brain dehydration."}
{"id": "PMID:213511", "title": "Characterization of high-affinity beta2-adrenergic receptor binding of (-)-[3H]-dihydroalprenolol to human polymorphonuclear cell particulates.", "content": "Human PMNs have well-described responses to beta-adrenergic catecholamines; these include elevation of cellular levels of cyclic AMP and inhibition of the release of lysosomal contents. Using the radioactive beta-adrenergic antagonist (-)-[3H]DHA in direct ligand-binding studies, we have identified and characterized beta-adrenergic receptors on particulate preparations of PMNs. These particulates bind DHA rapidly (t1/2 less than 1 min) and reversibly (t1/2 = 8 to 9 min). DHA binding is saturable and of high affinity (dissociation constant = 1 to 5 nM) and low capacity (870 +/- 128 receptors/cell, mean +/- S.D.) to a single class of binding sites. Competition for DHA binding sites by both beta-adrenergic agonists and antagonists is stereoselective [(-)-isomers more potent that (+)-isomers]. The rank order of potency of adrenergic agents in such competition studies indicates that these receptors are of the beta2 type. Since PMNs can be obtained in high purity with relative ease, the combined use of pharmacologic and ligand-binding studies in PMNs provide a useful system for studying beta-adrenergic receptors and their function in human subjects.", "contents": "Characterization of high-affinity beta2-adrenergic receptor binding of (-)-[3H]-dihydroalprenolol to human polymorphonuclear cell particulates. Human PMNs have well-described responses to beta-adrenergic catecholamines; these include elevation of cellular levels of cyclic AMP and inhibition of the release of lysosomal contents. Using the radioactive beta-adrenergic antagonist (-)-[3H]DHA in direct ligand-binding studies, we have identified and characterized beta-adrenergic receptors on particulate preparations of PMNs. These particulates bind DHA rapidly (t1/2 less than 1 min) and reversibly (t1/2 = 8 to 9 min). DHA binding is saturable and of high affinity (dissociation constant = 1 to 5 nM) and low capacity (870 +/- 128 receptors/cell, mean +/- S.D.) to a single class of binding sites. Competition for DHA binding sites by both beta-adrenergic agonists and antagonists is stereoselective [(-)-isomers more potent that (+)-isomers]. The rank order of potency of adrenergic agents in such competition studies indicates that these receptors are of the beta2 type. Since PMNs can be obtained in high purity with relative ease, the combined use of pharmacologic and ligand-binding studies in PMNs provide a useful system for studying beta-adrenergic receptors and their function in human subjects."}
{"id": "PMID:213512", "title": "A calibrated delivery system for inhalation challenge of toluene di-isocyanate vapor.", "content": "The vapor of TDI, a chemical commonly used in the plastics industry, may be associated with pulmonary symptoms at various concentrations. Because of the high volatility and adsorptivity of TDI, it has been difficult to deliver known, dilute concentrations of TDI to test subjects in inhalation challenge studies. A delivery system has been developed which can be calibrated to deliver an air-TDI mixture having a given flow rate and TDI concentration. The delivered gas stream is produced by diluting a gas stream having a low flow rate and a fixed concentration of TDI with a high-flow-rate stream of TDI-free air. A TDI detector continuously monitors the concentration of the resultant mixture, which is delivered to the subject by means of a face mask. For dilute mixtures, the output concentration is proportional to the ratio of the input flow rates; the proportionality factor depends on temperature and the geometry of the system. The flows for the described system could be regulated to produce concentrations in the range 0.0 to 0.08 ppm which remain stable to within +/- 10%.", "contents": "A calibrated delivery system for inhalation challenge of toluene di-isocyanate vapor. The vapor of TDI, a chemical commonly used in the plastics industry, may be associated with pulmonary symptoms at various concentrations. Because of the high volatility and adsorptivity of TDI, it has been difficult to deliver known, dilute concentrations of TDI to test subjects in inhalation challenge studies. A delivery system has been developed which can be calibrated to deliver an air-TDI mixture having a given flow rate and TDI concentration. The delivered gas stream is produced by diluting a gas stream having a low flow rate and a fixed concentration of TDI with a high-flow-rate stream of TDI-free air. A TDI detector continuously monitors the concentration of the resultant mixture, which is delivered to the subject by means of a face mask. For dilute mixtures, the output concentration is proportional to the ratio of the input flow rates; the proportionality factor depends on temperature and the geometry of the system. The flows for the described system could be regulated to produce concentrations in the range 0.0 to 0.08 ppm which remain stable to within +/- 10%."}
{"id": "PMID:213513", "title": "Effects of secretagogues and theophylline on canine gastric mucosal cyclic nucleotides.", "content": "cAMP and cGMP concentrations were measured in gastric mucosa in 18 anesthetized mongrel dogs receiving infusions of histamine (16 microgram/kg/hr), pentagastrin (6 microgram/kg/hr), bethanechol (10 microgram/kg/min), and theophylline (150 mg bolus, then 10 mg/min). The possible synergistic effect of continuous theophylline infusion with the secretagogues was studied in 15 other acute experiments. Antral and fundic mucosa were biopsied and measured by radioimmunoassay for cyclic nucleotides. All the secretagogues did not significantly change antral or fundic mucosal cyclic nucleotide concentrations compared to basal levels. In contrast, phosphodiesterase inhibition by theophylline significantly increased cAMP 11-fold and cGMP threefold in both antrum and fundus. Concomitant infusion of each secretagogue with theophylline did not potentiate the mucosal nucleotide response compared to theophylline alone. In a separate series of 19 experiments in three anesthetized dogs with vagally denervated fundic (Heidenhain) pouches, all the secretagogues which were infused in the same doses as in the acute biopsy studies produced maximal acid secretory responses. Theophylline, on the other hand, failed to stimulate acid secretion in five Heidenhain pouch experiments. These studies fail to implicate cyclic nucleotides as mediators of stimulated canine gastric acid secretion.", "contents": "Effects of secretagogues and theophylline on canine gastric mucosal cyclic nucleotides. cAMP and cGMP concentrations were measured in gastric mucosa in 18 anesthetized mongrel dogs receiving infusions of histamine (16 microgram/kg/hr), pentagastrin (6 microgram/kg/hr), bethanechol (10 microgram/kg/min), and theophylline (150 mg bolus, then 10 mg/min). The possible synergistic effect of continuous theophylline infusion with the secretagogues was studied in 15 other acute experiments. Antral and fundic mucosa were biopsied and measured by radioimmunoassay for cyclic nucleotides. All the secretagogues did not significantly change antral or fundic mucosal cyclic nucleotide concentrations compared to basal levels. In contrast, phosphodiesterase inhibition by theophylline significantly increased cAMP 11-fold and cGMP threefold in both antrum and fundus. Concomitant infusion of each secretagogue with theophylline did not potentiate the mucosal nucleotide response compared to theophylline alone. In a separate series of 19 experiments in three anesthetized dogs with vagally denervated fundic (Heidenhain) pouches, all the secretagogues which were infused in the same doses as in the acute biopsy studies produced maximal acid secretory responses. Theophylline, on the other hand, failed to stimulate acid secretion in five Heidenhain pouch experiments. These studies fail to implicate cyclic nucleotides as mediators of stimulated canine gastric acid secretion."}
{"id": "PMID:213514", "title": "Osteoclastoma of the petrous temporal bone.", "content": "This paper has described an unusual case of osteoclastoma of the petrous temporal bone which presented with multiple cranial neuropathies. A radical course of radiotherapy reversed the neuropathies but it is too early to comment on possible cure.", "contents": "Osteoclastoma of the petrous temporal bone. This paper has described an unusual case of osteoclastoma of the petrous temporal bone which presented with multiple cranial neuropathies. A radical course of radiotherapy reversed the neuropathies but it is too early to comment on possible cure."}
{"id": "PMID:213515", "title": "Idiopathic sensory trigeminal neuropathy.", "content": "A series of seven cases of isolated facial numbness is presented in whom the final diagnosis is considered to be idiopathic trigeminal neuropathy. Although this is a benign condition, careful work-up is needed, preferably by a team of specialists, in order to exclude more serious pathology. The team should include a neurologist, an otolaryngologist and a dental surgeon. By this means all other possible underlying diagnoses can be excluded. A list of differential diagnoses is discussed and the need for careful long-term follow-up is stressed.", "contents": "Idiopathic sensory trigeminal neuropathy. A series of seven cases of isolated facial numbness is presented in whom the final diagnosis is considered to be idiopathic trigeminal neuropathy. Although this is a benign condition, careful work-up is needed, preferably by a team of specialists, in order to exclude more serious pathology. The team should include a neurologist, an otolaryngologist and a dental surgeon. By this means all other possible underlying diagnoses can be excluded. A list of differential diagnoses is discussed and the need for careful long-term follow-up is stressed."}
{"id": "PMID:213516", "title": "Infratemporal fossa approach to tumours of the temporal bone and base of the skull.", "content": "In spite of the development of a superior (middle cranial fossa) and posterior (translabyrinthine) approach to the temporal bone, tumours situated in the infralabyrinthine and apical compartments of the pyramid and surrounding base of the skull were still a challenge for neurosurgeons and otologists as well. The infratemporal fossa approach closes the existing gap in the surgical management of the most hidden lesions of the temporal bone. The approach features the permanent anterior transposition of the facial nerve, resection of the mandibular condyle and mobilization of the zygoma and lateral orbital rim. Obliteration of the pneumatic spaces of the temporal bone, with permanent occlusion of the Eustachian tube and blind sac closure of the external auditory canal, avoids the danger of post-operative infection and leads to primary wound healing in the shortest time. Three types of infratemporal fossa approach are presented and dicussed on the basis of 51 operated patients.", "contents": "Infratemporal fossa approach to tumours of the temporal bone and base of the skull. In spite of the development of a superior (middle cranial fossa) and posterior (translabyrinthine) approach to the temporal bone, tumours situated in the infralabyrinthine and apical compartments of the pyramid and surrounding base of the skull were still a challenge for neurosurgeons and otologists as well. The infratemporal fossa approach closes the existing gap in the surgical management of the most hidden lesions of the temporal bone. The approach features the permanent anterior transposition of the facial nerve, resection of the mandibular condyle and mobilization of the zygoma and lateral orbital rim. Obliteration of the pneumatic spaces of the temporal bone, with permanent occlusion of the Eustachian tube and blind sac closure of the external auditory canal, avoids the danger of post-operative infection and leads to primary wound healing in the shortest time. Three types of infratemporal fossa approach are presented and dicussed on the basis of 51 operated patients."}
{"id": "PMID:213517", "title": "Intracisternal tubular inclusions in nasopharyngeal carcinoma.", "content": "Biopsy specimens obtained from 20 cases of nasopharyngeal carcinoma were examined under electronmicroscope for the presence of Intracisternal Tubular Inclusions (ITI). In eight (40 per cent) of them these inclusions could be identified. Although the morphogenesis and significance of these ITI are not clearly understood, they have been found in several autoimmune and viral diseases, including infectious mononucleosis, a disease caused by EBV, and Burkitt's lymphoma, which is closely associated with EBV. Hence, the presence of ITI in NPC, another disease associated with EBV, seems to be of some significance. It is proposed that these inclusions could be the result of an immunological reaction initiated by injured cells infected with EBV, which acted as an antigen. The presence of another type of cytoplasmic inclusion, hitherto unknown, has also been reported.", "contents": "Intracisternal tubular inclusions in nasopharyngeal carcinoma. Biopsy specimens obtained from 20 cases of nasopharyngeal carcinoma were examined under electronmicroscope for the presence of Intracisternal Tubular Inclusions (ITI). In eight (40 per cent) of them these inclusions could be identified. Although the morphogenesis and significance of these ITI are not clearly understood, they have been found in several autoimmune and viral diseases, including infectious mononucleosis, a disease caused by EBV, and Burkitt's lymphoma, which is closely associated with EBV. Hence, the presence of ITI in NPC, another disease associated with EBV, seems to be of some significance. It is proposed that these inclusions could be the result of an immunological reaction initiated by injured cells infected with EBV, which acted as an antigen. The presence of another type of cytoplasmic inclusion, hitherto unknown, has also been reported."}
{"id": "PMID:213518", "title": "The binding isotherms for the interaction of 5-doxyl stearic acid with bovine and human albumin.", "content": "Binding isotherms for the interaction of 5-doxyl stearic acid with bovine and human albumin are reported. The critical micelle concentration (CMC) and the limiting solubility of 5-doxyl stearic acid were determined using the electron spin resonance (ESR)-spin label method. The CMC and the limiting solubility of this spin-label stearic acid in saline-phosphate buffer are 3.5 x 10(-5) M and 2 x 10(-4) M, respectively. We found no ESR line width evidence for pre-association of the spin-label stearate below the CMC. Maximum binding of the spin-label stearate to both bovine and human albumin occurs before micelle formation. The binding isotherm for spin-label stearic acid interaction with bovine albumin is in agreement with data obtained by others using [1-(14)C]stearic acid. For human albumin, comparison is difficult since previous data obtained with [1-(14)C]stearic acid vary widely. Comparison of the ESR 2T(||) values (the splitting between low and high field extremes, a measure of the degree of immobilization of protein-bound spin-label stearate) for bovine and human albumin indicates a greater immobilization of the spin-label molecules bound to human albumin. The binding data indicate that complexes are formed with bound spin-label stearate/albumin ratios of at least 18. The computed equilibrium constants for both bovine and human albumin indicate that the first seven spin-label molecules are tightly bound, log K > 5.0. The species predicted to form in solution by these equilibrium constants are reported.", "contents": "The binding isotherms for the interaction of 5-doxyl stearic acid with bovine and human albumin. Binding isotherms for the interaction of 5-doxyl stearic acid with bovine and human albumin are reported. The critical micelle concentration (CMC) and the limiting solubility of 5-doxyl stearic acid were determined using the electron spin resonance (ESR)-spin label method. The CMC and the limiting solubility of this spin-label stearic acid in saline-phosphate buffer are 3.5 x 10(-5) M and 2 x 10(-4) M, respectively. We found no ESR line width evidence for pre-association of the spin-label stearate below the CMC. Maximum binding of the spin-label stearate to both bovine and human albumin occurs before micelle formation. The binding isotherm for spin-label stearic acid interaction with bovine albumin is in agreement with data obtained by others using [1-(14)C]stearic acid. For human albumin, comparison is difficult since previous data obtained with [1-(14)C]stearic acid vary widely. Comparison of the ESR 2T(||) values (the splitting between low and high field extremes, a measure of the degree of immobilization of protein-bound spin-label stearate) for bovine and human albumin indicates a greater immobilization of the spin-label molecules bound to human albumin. The binding data indicate that complexes are formed with bound spin-label stearate/albumin ratios of at least 18. The computed equilibrium constants for both bovine and human albumin indicate that the first seven spin-label molecules are tightly bound, log K > 5.0. The species predicted to form in solution by these equilibrium constants are reported."}
{"id": "PMID:213519", "title": "Evaluation of a radioimmunoassay for plasma adrenocorticotrophin.", "content": "A radioimmunoassay for plasma ACTH has been described and evaluated. Rabbit antiserum produced by immunization with [Asp25, Ala26, Gly27,]-alphah-corticotrophin-(1--28)-octacosa-peptide (a sequence analogue of alphah1--28-ACTH) bovine gamma globulin conjugate was used. The antiserum is specific for the NH2-terminal portion of the ACTH molecule and cross-reactivity of human, porcine and rat ACTH in the system has been demonstrated. Reasonable agreement was found between estimates obtained by bioassay and radio-immunoassay of the ACTH content of rat pituitary gland incubation media, indicating a close relationship between the sequence of ACTH recognized by the antibodies and the sequence possessing the steroidogenic activity. Measurement of the amount of ACTH in the plasma required the preliminary extraction and concentration of the hormone. Over a range of concentrations between 3.5 and 3600 pg/ml, extraction recovery was independent of the initial concentration of ACTH in the plasma. Extraction gave rise to no changes in the immunological properties of standard ACTH. The concentration of immunoreactive ACTH in rat plasma was 48 +/- 3.6 (S.E.M.) pg/ml in the morning and 106 +/- 9.9 pg/ml in the afternoon. Exposure to either for 5 min and subsequent laparotomy gave rise to a significant increase in the concentration of immunoreactive ACTH in the plasma. The resting level of ACTH and the ACTH response to stress were both significantly higher 1 and 7 days after adrenalectomy. Intravenous injection of a hypothalamic extract elicited a considerable rise in the concentration of immunoreactive ACTH in the plasma, but no response was seen after oral administration of this partially purified extract. The sensitivity, precision and specificity of this ACTH radioimmunoassay make it a useful tool for studying pituitary--adrenal physiology.", "contents": "Evaluation of a radioimmunoassay for plasma adrenocorticotrophin. A radioimmunoassay for plasma ACTH has been described and evaluated. Rabbit antiserum produced by immunization with [Asp25, Ala26, Gly27,]-alphah-corticotrophin-(1--28)-octacosa-peptide (a sequence analogue of alphah1--28-ACTH) bovine gamma globulin conjugate was used. The antiserum is specific for the NH2-terminal portion of the ACTH molecule and cross-reactivity of human, porcine and rat ACTH in the system has been demonstrated. Reasonable agreement was found between estimates obtained by bioassay and radio-immunoassay of the ACTH content of rat pituitary gland incubation media, indicating a close relationship between the sequence of ACTH recognized by the antibodies and the sequence possessing the steroidogenic activity. Measurement of the amount of ACTH in the plasma required the preliminary extraction and concentration of the hormone. Over a range of concentrations between 3.5 and 3600 pg/ml, extraction recovery was independent of the initial concentration of ACTH in the plasma. Extraction gave rise to no changes in the immunological properties of standard ACTH. The concentration of immunoreactive ACTH in rat plasma was 48 +/- 3.6 (S.E.M.) pg/ml in the morning and 106 +/- 9.9 pg/ml in the afternoon. Exposure to either for 5 min and subsequent laparotomy gave rise to a significant increase in the concentration of immunoreactive ACTH in the plasma. The resting level of ACTH and the ACTH response to stress were both significantly higher 1 and 7 days after adrenalectomy. Intravenous injection of a hypothalamic extract elicited a considerable rise in the concentration of immunoreactive ACTH in the plasma, but no response was seen after oral administration of this partially purified extract. The sensitivity, precision and specificity of this ACTH radioimmunoassay make it a useful tool for studying pituitary--adrenal physiology."}
{"id": "PMID:213520", "title": "Activity of the pituitary-adrenocortical system and thyroid gland during the oestrous cycle of the rat.", "content": "The concentrations of LH, progesterone, ACTH, corticosterone and thyroxine in the plasma were estimated at various times during the oestrous cycle of the rat. The well-established patterns of LH and progesterone secretion were confirmed. On each day of the cycle the plasma concentrations of ACTH and corticosterone were lowest in the morning and rose in the afternoon. Conversely, during oestrus and dioestrus, the plasma concentrations of thyroxine were higher in the morning than in the evening. However, during the afternoon of pro-oestrus the concentrations of ACTH, corticosterone and thyroxine in the plasma rose and, like the concentrations of LH and progesterone, all reached levels far higher than those attained at any other time of the cycle.", "contents": "Activity of the pituitary-adrenocortical system and thyroid gland during the oestrous cycle of the rat. The concentrations of LH, progesterone, ACTH, corticosterone and thyroxine in the plasma were estimated at various times during the oestrous cycle of the rat. The well-established patterns of LH and progesterone secretion were confirmed. On each day of the cycle the plasma concentrations of ACTH and corticosterone were lowest in the morning and rose in the afternoon. Conversely, during oestrus and dioestrus, the plasma concentrations of thyroxine were higher in the morning than in the evening. However, during the afternoon of pro-oestrus the concentrations of ACTH, corticosterone and thyroxine in the plasma rose and, like the concentrations of LH and progesterone, all reached levels far higher than those attained at any other time of the cycle."}
{"id": "PMID:213523", "title": "Effects of human thyroid-stimulating hormone and immunoglobulins on adenylate cyclase activity and the accumulation of cyclic AMP in human thyroid membranes and slices.", "content": "The activation of adenylate cyclase and the accumulation of cyclic AMP resulting from the action of human thyroid-stimulating hormone (TSH), long-acting thyroid stimulator (LATS) or LATS-protector (LATS-P) have been investigated in preparations of human thyroid membranes and slices. Human TSH significantly increased adenylate cyclase activity in membranes from non-toxic goitres whereas LATS and LATS-P had no consistent effect. However, pre-incubation of goitrous membranes with LATS--immunoglobulin G inhibited the effect of TSH on adenylate cyclase. When thyroid membranes were prepared from the glands of patients with Graves's disease neither TSH nor thyroid-stimulating immunoglobulins (TSIg) stimulated adenylate cyclase significantly. Whether from non-toxic goitres or thyrotoxic tissue, the concentration of TSH needed to induce half of the maximum response was lower in thyroid slices than in membranes. Both LATS and LATS-P significantly stimulated the accumulation of cyclic AMP in slices of goitrous tissue but thyrotoxic tissue slices did not respond. In goitrous slices, submaximum concentrations of TSH and TSIg caused additive responses in the accumulation of cyclic AMP but TSIg did not increase the maximum response to TSH.", "contents": "Effects of human thyroid-stimulating hormone and immunoglobulins on adenylate cyclase activity and the accumulation of cyclic AMP in human thyroid membranes and slices. The activation of adenylate cyclase and the accumulation of cyclic AMP resulting from the action of human thyroid-stimulating hormone (TSH), long-acting thyroid stimulator (LATS) or LATS-protector (LATS-P) have been investigated in preparations of human thyroid membranes and slices. Human TSH significantly increased adenylate cyclase activity in membranes from non-toxic goitres whereas LATS and LATS-P had no consistent effect. However, pre-incubation of goitrous membranes with LATS--immunoglobulin G inhibited the effect of TSH on adenylate cyclase. When thyroid membranes were prepared from the glands of patients with Graves's disease neither TSH nor thyroid-stimulating immunoglobulins (TSIg) stimulated adenylate cyclase significantly. Whether from non-toxic goitres or thyrotoxic tissue, the concentration of TSH needed to induce half of the maximum response was lower in thyroid slices than in membranes. Both LATS and LATS-P significantly stimulated the accumulation of cyclic AMP in slices of goitrous tissue but thyrotoxic tissue slices did not respond. In goitrous slices, submaximum concentrations of TSH and TSIg caused additive responses in the accumulation of cyclic AMP but TSIg did not increase the maximum response to TSH."}
{"id": "PMID:213524", "title": "Distribution of androgen metabolizing enzymes in isolated tissues of human forehead and axillary skin.", "content": "The distribution of androgen metabolism in human skin was studied using tissues isolated either by direct dissection of axillary skin or by dissection of collagenase-digested forehead and axillary skin. All tissues (epidermis, sweat glands, sebaceous glands, hair follicles and dermis) were found to contain 17beta-, 3beta- and 3alpha-hydroxysteroid dehydrogenase (HSD) activities, 3beta-hydroxysteroid dehydrogenase-delta4--5 isomerase (delta5-3beta-HSD) activity and 5alpha-reductase activity. All tissues converted testosterone into 5alpha-dihydrotestosterone. In confirmation of previous histochemical studies, over 90% of the delta5-3beta-HSD of forehead skin was found in the sebaceous glands. In forehead skin, 40--66% of the 5alpha-reductase activity was in the sebaceous glands, while in axillary skin 50--70% was in the sweat glands, especially the apocrine glands. There was a more even distribution of 17beta-HSD activity in skin tissues than histochemical studies have indicated previously. Knowledge of the distribution of these enzymes has helped in the understanding of the function of androgen metabolism in skin.", "contents": "Distribution of androgen metabolizing enzymes in isolated tissues of human forehead and axillary skin. The distribution of androgen metabolism in human skin was studied using tissues isolated either by direct dissection of axillary skin or by dissection of collagenase-digested forehead and axillary skin. All tissues (epidermis, sweat glands, sebaceous glands, hair follicles and dermis) were found to contain 17beta-, 3beta- and 3alpha-hydroxysteroid dehydrogenase (HSD) activities, 3beta-hydroxysteroid dehydrogenase-delta4--5 isomerase (delta5-3beta-HSD) activity and 5alpha-reductase activity. All tissues converted testosterone into 5alpha-dihydrotestosterone. In confirmation of previous histochemical studies, over 90% of the delta5-3beta-HSD of forehead skin was found in the sebaceous glands. In forehead skin, 40--66% of the 5alpha-reductase activity was in the sebaceous glands, while in axillary skin 50--70% was in the sweat glands, especially the apocrine glands. There was a more even distribution of 17beta-HSD activity in skin tissues than histochemical studies have indicated previously. Knowledge of the distribution of these enzymes has helped in the understanding of the function of androgen metabolism in skin."}
{"id": "PMID:213525", "title": "Na++K+-ATPase in the osmoregulating clam Rangia cuneata.", "content": "Of six tissues sampled from the osmoregulating clam Rangia cuneata, mantle contained the highest concentration of Na++K+-ATPase activity and ouabain binding sites. Acclimation to low salinities was accompanied by adaptive increases in Na++K+-ATPase activity in mantle but not in gill. Since the number of ouabain binding sites did not show parallel increases, the mechanism of acclimation to reduced salinity in Rangia appears to involve activation of pre-existing pump sites in the mantle epithelium.", "contents": "Na++K+-ATPase in the osmoregulating clam Rangia cuneata. Of six tissues sampled from the osmoregulating clam Rangia cuneata, mantle contained the highest concentration of Na++K+-ATPase activity and ouabain binding sites. Acclimation to low salinities was accompanied by adaptive increases in Na++K+-ATPase activity in mantle but not in gill. Since the number of ouabain binding sites did not show parallel increases, the mechanism of acclimation to reduced salinity in Rangia appears to involve activation of pre-existing pump sites in the mantle epithelium."}
{"id": "PMID:213527", "title": "Some structural antigens of herpes simplex virus type 1.", "content": "Several of the major structural polypeptides of herpes simplex virus were obtained in purified form by polyacrylamide gel electrophoresis of purified virus particle polypeptides. Antisera made by footpad inoculation of these polypeptides into rabbits were used to study the antigenic properties of two envelope glycoproteins and of the major capsid protein.", "contents": "Some structural antigens of herpes simplex virus type 1. Several of the major structural polypeptides of herpes simplex virus were obtained in purified form by polyacrylamide gel electrophoresis of purified virus particle polypeptides. Antisera made by footpad inoculation of these polypeptides into rabbits were used to study the antigenic properties of two envelope glycoproteins and of the major capsid protein."}
{"id": "PMID:213528", "title": "The fate of protein subunits of parainfluenza (Sendai) virus after adsorption to NIL8 hamster embryo cells.", "content": "Adsorption of u.v.-inactivated Sendai virus on to NIL8 hamster cells causes fusion of the cells into polykaryocytes within 2 h. \"Infected\" cells were incubated at 37 degrees C for periods of 10 min to 8 h and their surface proteins iodinated with [125I] catalysed by peroxidase. Structural components of the viral envelope, such as haemagglutin-neuraminidase (HN) and probably also the fusion protein (F) were detected in the cell membrane for periods up to 4 h post infection.", "contents": "The fate of protein subunits of parainfluenza (Sendai) virus after adsorption to NIL8 hamster embryo cells. Adsorption of u.v.-inactivated Sendai virus on to NIL8 hamster cells causes fusion of the cells into polykaryocytes within 2 h. \"Infected\" cells were incubated at 37 degrees C for periods of 10 min to 8 h and their surface proteins iodinated with [125I] catalysed by peroxidase. Structural components of the viral envelope, such as haemagglutin-neuraminidase (HN) and probably also the fusion protein (F) were detected in the cell membrane for periods up to 4 h post infection."}
{"id": "PMID:213530", "title": "Poliovirus polypeptides examined in more detail.", "content": "The pattern of viral polypeptide synthesis and cleavage in poliovirus-infected cells was shown by autoradiography to be considerably more complex than previously thought. In normal growth, at least 26 distinct polypeptides were found, and various modifications of the cleavage process revealed a total of at least 34. Most of the new polypeptides were minor components that were unstable during a chase. Different cultural modifications led to different polypeptide ratios, and it appeared likely that several cleavage activities were involved . Minor differences were found in the polypeptide contents of cytoplasmic extracts and whole infected cells. The complexity of the cleavage pattern necessitated a new nomenclature based on mol. wt. (e.g. Pp110, \"poliovirus protein\" of 110000). Particular attention was paid to mol. wt. determinations, notably in the use of internal protein standards and more fully denaturing gel conditions. The size of the \"primary translation product\" of poliovirus RNA was found to be 210000 daltons, so that either 20% of the viral genome is not translated in vivo, or some is read as a smaller independent translation unit.", "contents": "Poliovirus polypeptides examined in more detail. The pattern of viral polypeptide synthesis and cleavage in poliovirus-infected cells was shown by autoradiography to be considerably more complex than previously thought. In normal growth, at least 26 distinct polypeptides were found, and various modifications of the cleavage process revealed a total of at least 34. Most of the new polypeptides were minor components that were unstable during a chase. Different cultural modifications led to different polypeptide ratios, and it appeared likely that several cleavage activities were involved . Minor differences were found in the polypeptide contents of cytoplasmic extracts and whole infected cells. The complexity of the cleavage pattern necessitated a new nomenclature based on mol. wt. (e.g. Pp110, \"poliovirus protein\" of 110000). Particular attention was paid to mol. wt. determinations, notably in the use of internal protein standards and more fully denaturing gel conditions. The size of the \"primary translation product\" of poliovirus RNA was found to be 210000 daltons, so that either 20% of the viral genome is not translated in vivo, or some is read as a smaller independent translation unit."}
{"id": "PMID:213531", "title": "Relations between poliovirus polypeptides as shown by tryptic peptide analysis.", "content": "Poliovirus proteins were labelled in vivo with [35S]-methionine, and the major products of translation and cleavage were separated by electrophoresis and compared in terms of two-dimensional tryptic peptide maps visualized by autoradiography. The main intermediates p110 and p90 had few or no methionine-labelled sequences in common, but were both contained in, and therefore almost fully account for, the presumed primary translation product p210. The sequences of p79, a major stable product of cleavage and a non-structural protein, were almost completely contained in p90, which in turn is the major component of the larger intermediates p168 and p155. P110 is confirmed as the precursor of virus particle protein, and VP0 as the precursor of VP2. However, the sequences of p31, the other major product of translation that is not a stuctural protein, were not contained in any of the viral polypeptides mentioned above.", "contents": "Relations between poliovirus polypeptides as shown by tryptic peptide analysis. Poliovirus proteins were labelled in vivo with [35S]-methionine, and the major products of translation and cleavage were separated by electrophoresis and compared in terms of two-dimensional tryptic peptide maps visualized by autoradiography. The main intermediates p110 and p90 had few or no methionine-labelled sequences in common, but were both contained in, and therefore almost fully account for, the presumed primary translation product p210. The sequences of p79, a major stable product of cleavage and a non-structural protein, were almost completely contained in p90, which in turn is the major component of the larger intermediates p168 and p155. P110 is confirmed as the precursor of virus particle protein, and VP0 as the precursor of VP2. However, the sequences of p31, the other major product of translation that is not a stuctural protein, were not contained in any of the viral polypeptides mentioned above."}
{"id": "PMID:213532", "title": "A high density component in several vertebrate enteroviruses.", "content": "In addition to the major infective component, which bands at a density of 1:34 g/ml in caesium chloride (\"light component\"), a component with a density of 1:44 g/ml (\"heavy component\") has been found in harvests of poliovirus (type I), Coxsackie B5 virus, a bovine enterovirus (VG-5-27) and swine vesicular disease virus (SVDV). With SVDV about 98% of the infectivity equilibrated at 1 . 34 g/ml but approx. 2% was present as a peak at 1 . 44 g/ml. The morphology of the two forms was similar but the heavy component had a smaller diameter (28 nm) than the light component (30 nm). No inter-conversion of the two forms was observed on re-cycling in fresh caesium chloride gradients and the two components had the same proportions of RNA and protein and the same polypeptide composition. Each component gave a similar proportion of the light and heavy forms on replication, but the light component had a specific infectivity about fourfold higher than that of the heavy component and was also much more efficient in eliciting the formation of neutralizing antibodies in guinea pigs. Although these results suggest that the two particles are alternative stable configurations of the virus, iodination failed to reveal any differences in the extent or pattern of labelling of the polypeptides in the two forms.", "contents": "A high density component in several vertebrate enteroviruses. In addition to the major infective component, which bands at a density of 1:34 g/ml in caesium chloride (\"light component\"), a component with a density of 1:44 g/ml (\"heavy component\") has been found in harvests of poliovirus (type I), Coxsackie B5 virus, a bovine enterovirus (VG-5-27) and swine vesicular disease virus (SVDV). With SVDV about 98% of the infectivity equilibrated at 1 . 34 g/ml but approx. 2% was present as a peak at 1 . 44 g/ml. The morphology of the two forms was similar but the heavy component had a smaller diameter (28 nm) than the light component (30 nm). No inter-conversion of the two forms was observed on re-cycling in fresh caesium chloride gradients and the two components had the same proportions of RNA and protein and the same polypeptide composition. Each component gave a similar proportion of the light and heavy forms on replication, but the light component had a specific infectivity about fourfold higher than that of the heavy component and was also much more efficient in eliciting the formation of neutralizing antibodies in guinea pigs. Although these results suggest that the two particles are alternative stable configurations of the virus, iodination failed to reveal any differences in the extent or pattern of labelling of the polypeptides in the two forms."}
{"id": "PMID:213533", "title": "Complementation of adeno-associated virus growth with temperature-sensitive mutants of human adenovirus types 12 and 5.", "content": "Temperature-sensitive mutants of human adenovirus types 12 and 5, defective in viral DNA synthesis, were able to support growth of adeno-associated virus type I at the non-permissive temperature.", "contents": "Complementation of adeno-associated virus growth with temperature-sensitive mutants of human adenovirus types 12 and 5. Temperature-sensitive mutants of human adenovirus types 12 and 5, defective in viral DNA synthesis, were able to support growth of adeno-associated virus type I at the non-permissive temperature."}
{"id": "PMID:213534", "title": "Effect of isoleucine deprivation of rabbitpox virus DNA synthesis in mouse L cells.", "content": "Synthesis of rabbitpox DNA was inhibited in mouse L cells deprived of isoleucine. Time-course patterns of incorporation of radiolabelled precursors into viral DNA revealed that synthesis of viral DNA began about 6 h after reversal of the isoleucine-deficient state.", "contents": "Effect of isoleucine deprivation of rabbitpox virus DNA synthesis in mouse L cells. Synthesis of rabbitpox DNA was inhibited in mouse L cells deprived of isoleucine. Time-course patterns of incorporation of radiolabelled precursors into viral DNA revealed that synthesis of viral DNA began about 6 h after reversal of the isoleucine-deficient state."}
{"id": "PMID:213535", "title": "Hyperpolarizing potentials induced by Ca-mediated K-conductance increase in hamster submandibular ganglion cells.", "content": "The mechanisms of three types of hyperpolarizing electrogenesis in hamster submandibular ganglion cells were analyzed with intracellular microelectrodes. These included (1) spike-induced hyperpolarizing afterpotential (S-HAP), (2) spontaneous transient hyperpolarizing potential (HP), and (3) the hyperpolarizing (H) phase of postsynaptic potential (PSP). Most of these hyperpolarizing potentials were due to conductance increases and reversed polarity at membrane potential (Em) between -70 and -85 mV, which was close to the K-equilibrium potential. The average resting potential of ganglion cells was -53 mV. Action potential overshoot increased slightly in high [Ca2+]0 and decreased in low [Ca2+]0. In most neurons action potentials were completely suppressed by 10(-7)-M tetrodotoxin (TTX). The S-HAP has an initial component due to delayed rectification and a late component. The late component is enhanced by increasing [Ca2+]0, or by applying Ca-ionophore (A23187), TEA, caffeine, or dibutyryl cyclic (DBc-) AMP; it is suppressed by decreasing [Ca2+]0, or by applying Mn2+. Perfusion with Cl--free saline reduced membrane potential slightly but did not modify the S-HAP. Depolarizing pulses also induced hyperpolarizing afterpotential (D-HAP), similar to the S-HAP. Spontaneous transient HPs occurred in some neurons at irregular intervals. HPs were insensitive to TTX but were suppressed by Mn2+. Caffeine induced low frequency rhythmic HPs in many neurons, often alternating with periods of repetitive spiking. The PSP was a monophasic depolarizing (D-) potential in some neurons, but in others the D-phase was followed by a small H-phase. Perfusion with A23187, caffeine or DBc-AMP increased the H-phase of the PSP. Perfusion with K+-free saline or treatment with 10(-5)M ouabain did not abolish the H-phase of PSPs. These membrane potential-dependent phenomena appear to be induced mainly by Ca-mediated K-conductance increases. This mechanism contributes to the regulation of low-frequency repetitive firing in submandibular ganglion cells.", "contents": "Hyperpolarizing potentials induced by Ca-mediated K-conductance increase in hamster submandibular ganglion cells. The mechanisms of three types of hyperpolarizing electrogenesis in hamster submandibular ganglion cells were analyzed with intracellular microelectrodes. These included (1) spike-induced hyperpolarizing afterpotential (S-HAP), (2) spontaneous transient hyperpolarizing potential (HP), and (3) the hyperpolarizing (H) phase of postsynaptic potential (PSP). Most of these hyperpolarizing potentials were due to conductance increases and reversed polarity at membrane potential (Em) between -70 and -85 mV, which was close to the K-equilibrium potential. The average resting potential of ganglion cells was -53 mV. Action potential overshoot increased slightly in high [Ca2+]0 and decreased in low [Ca2+]0. In most neurons action potentials were completely suppressed by 10(-7)-M tetrodotoxin (TTX). The S-HAP has an initial component due to delayed rectification and a late component. The late component is enhanced by increasing [Ca2+]0, or by applying Ca-ionophore (A23187), TEA, caffeine, or dibutyryl cyclic (DBc-) AMP; it is suppressed by decreasing [Ca2+]0, or by applying Mn2+. Perfusion with Cl--free saline reduced membrane potential slightly but did not modify the S-HAP. Depolarizing pulses also induced hyperpolarizing afterpotential (D-HAP), similar to the S-HAP. Spontaneous transient HPs occurred in some neurons at irregular intervals. HPs were insensitive to TTX but were suppressed by Mn2+. Caffeine induced low frequency rhythmic HPs in many neurons, often alternating with periods of repetitive spiking. The PSP was a monophasic depolarizing (D-) potential in some neurons, but in others the D-phase was followed by a small H-phase. Perfusion with A23187, caffeine or DBc-AMP increased the H-phase of the PSP. Perfusion with K+-free saline or treatment with 10(-5)M ouabain did not abolish the H-phase of PSPs. These membrane potential-dependent phenomena appear to be induced mainly by Ca-mediated K-conductance increases. This mechanism contributes to the regulation of low-frequency repetitive firing in submandibular ganglion cells."}
{"id": "PMID:213536", "title": "A second brain tumour and irradiation.", "content": "Three patients are described in whom irradiation of 2750 rad or more was used in the management of primary brain tumours, and 21 years or more later a second brain tumour of a different type occurred. One of the new tumours was a meningioma and the other two were cerebral astrocytomas. There is evidence to show that moderate doses of ionising radiations given in childhood for tinea capitis are associated with a late risk of developing a meningioma. Higher doses of radiation used for tumours in childhood are followed also by a late hazard of meningioma. There is insufficient evidence to implicate ionising radiations in the aetiology of gliomas. The oncogenic hazards of radiotherapy to the brain do not outweigh its therapeutic value in brain tumour.", "contents": "A second brain tumour and irradiation. Three patients are described in whom irradiation of 2750 rad or more was used in the management of primary brain tumours, and 21 years or more later a second brain tumour of a different type occurred. One of the new tumours was a meningioma and the other two were cerebral astrocytomas. There is evidence to show that moderate doses of ionising radiations given in childhood for tinea capitis are associated with a late risk of developing a meningioma. Higher doses of radiation used for tumours in childhood are followed also by a late hazard of meningioma. There is insufficient evidence to implicate ionising radiations in the aetiology of gliomas. The oncogenic hazards of radiotherapy to the brain do not outweigh its therapeutic value in brain tumour."}
{"id": "PMID:213537", "title": "Myasthenia in patients with dermatomyositis: clinical, electrophysiological and ultrastructural studies.", "content": "In 4 patients with clinical signs of dermatomyositis, confirmed by electromyography and muscle biopsy, a form of muscle fatigue was detected which was expressed clinically by predominantly proximal motor deficit, with phonation and deglutition disturbances, slightly influenced by prostigmine. In all patients, stimulation of the ulnar nerve at 3--10 Hz induced a decrement of muscle-evoked potentials in abductor digiti minimi and at 15--50 Hz an increment at the end of the trains (1.2 sec in duration) of repetitive stimulation (preceded in two cases by a decrement in the response to the fifth stimulus in the train). Stimulation at 30 Hz for 10 sec resulted in a transient facilitation, followed (at 3 Hz stimulation) by postactivation exhaustion which disappeared after 5--15 min. The post-tetanic facilitation, the incremental response and the myasthenic symptoms reverted to normal under treatment with corticosteroids, an immunosuppressor agent and guanidine hydrochloride. A mixed, pre- and postsynaptic mechanism is presumed to underlie the muscle fatigue in our patients. Electron microscopy of muscle biopsies disclosed zones of necrosis and, in incipient stages, large agglomerations of glycogen that had disorganized the structure of myofibrils. The end-plates in the biopsies were larger than normal and the cholinesterase reaction was hyperactive. Serum immunoelectrophoretic and electrophoretic data--increase of IgG and IgM, decrease of IgA and hypergammaglobulinaemia -- point to a possible autoimmune mechanism of the neuromuscular disorders in our patients.", "contents": "Myasthenia in patients with dermatomyositis: clinical, electrophysiological and ultrastructural studies. In 4 patients with clinical signs of dermatomyositis, confirmed by electromyography and muscle biopsy, a form of muscle fatigue was detected which was expressed clinically by predominantly proximal motor deficit, with phonation and deglutition disturbances, slightly influenced by prostigmine. In all patients, stimulation of the ulnar nerve at 3--10 Hz induced a decrement of muscle-evoked potentials in abductor digiti minimi and at 15--50 Hz an increment at the end of the trains (1.2 sec in duration) of repetitive stimulation (preceded in two cases by a decrement in the response to the fifth stimulus in the train). Stimulation at 30 Hz for 10 sec resulted in a transient facilitation, followed (at 3 Hz stimulation) by postactivation exhaustion which disappeared after 5--15 min. The post-tetanic facilitation, the incremental response and the myasthenic symptoms reverted to normal under treatment with corticosteroids, an immunosuppressor agent and guanidine hydrochloride. A mixed, pre- and postsynaptic mechanism is presumed to underlie the muscle fatigue in our patients. Electron microscopy of muscle biopsies disclosed zones of necrosis and, in incipient stages, large agglomerations of glycogen that had disorganized the structure of myofibrils. The end-plates in the biopsies were larger than normal and the cholinesterase reaction was hyperactive. Serum immunoelectrophoretic and electrophoretic data--increase of IgG and IgM, decrease of IgA and hypergammaglobulinaemia -- point to a possible autoimmune mechanism of the neuromuscular disorders in our patients."}
{"id": "PMID:213538", "title": "Lipid storage myopathy in von Gierke's disease: a case report.", "content": "An 18-year-old girl with von Gierke's disease associated with a lipid storage myopathy is reported. The diagnosis of von Gierke's disease was made from decreased activity in glucose-6-phosphatase in the jejunal biopsy specimen. Neurologically she showed generalized hypotonia of the muscles, atrophy of bilateral proximal muscles of the lower extremities, weakness in neck flexors, deltoid and lumbar girdle muscles, and a positive Gower's sign. Muscle biopsy from flexor femoris muscle revealed fatty deposition in type 1 fibers and atrophy of type 2 fibers and the diagnosis of an accompanying lipid storage myopathy was made. This case also had a ventricular septal defect confirmed by right cardiac catheterization.", "contents": "Lipid storage myopathy in von Gierke's disease: a case report. An 18-year-old girl with von Gierke's disease associated with a lipid storage myopathy is reported. The diagnosis of von Gierke's disease was made from decreased activity in glucose-6-phosphatase in the jejunal biopsy specimen. Neurologically she showed generalized hypotonia of the muscles, atrophy of bilateral proximal muscles of the lower extremities, weakness in neck flexors, deltoid and lumbar girdle muscles, and a positive Gower's sign. Muscle biopsy from flexor femoris muscle revealed fatty deposition in type 1 fibers and atrophy of type 2 fibers and the diagnosis of an accompanying lipid storage myopathy was made. This case also had a ventricular septal defect confirmed by right cardiac catheterization."}
{"id": "PMID:213539", "title": "Periodic nocturnal myoclonus in a patient with hyperexplexia (startle disease).", "content": "The periodic nocturnal myoclonus of a patient with hyperexplexia has been studied. Evidence has been given that the jerks are spontaneous arousal reactions. The temporal characteristics of the jerks have been analysed. The jerks appear to be correlated with the respiratory rhythm and the data suggest a correlation of the jerks with circulatory and respiratory higher order waves. The results are discussed with relation to the literature concerning spontaneous sleep jerks.", "contents": "Periodic nocturnal myoclonus in a patient with hyperexplexia (startle disease). The periodic nocturnal myoclonus of a patient with hyperexplexia has been studied. Evidence has been given that the jerks are spontaneous arousal reactions. The temporal characteristics of the jerks have been analysed. The jerks appear to be correlated with the respiratory rhythm and the data suggest a correlation of the jerks with circulatory and respiratory higher order waves. The results are discussed with relation to the literature concerning spontaneous sleep jerks."}
{"id": "PMID:213540", "title": "Hypothalamic hypothyroidism and hypogonadism in prolonged traumatic coma.", "content": "Prolonged coma afterhead trauma is associated with depletion of 3', 5' cyclic adenosine monophosphate (cAMP) in the cerebrospinal fluid (CSF). Because cAMP has previously been implicated in neurorendocrine secretion, this study examines the pituitay-hypothalamic function in 15 adult male patients (to exclude the effects of puberty and menses) with traumatic coma lasting longer than 2 weeks. Ventricular CSF cAMP was measured at 2- to 4-day intervals for 10 to 25 days. Simultaneously, plasma hormone concentrations were also determined. In all 15 cases, CSF cAMP and plasma levels of thyroid-stimulating hormone (TSH), thyroxine (T4), free T4, triiodothyronine (T3), luteinzing hormone (LH), follicle-stimulating hormone (FSH), and testerone became subnormal. In 11 patients whose level of consciousness fluctuated, the reduction in plasma T4 and testerone were proportional to both severity of coma ( r greater than 0.81, p less than 0.05) and depletion of CSF cAMP (r greater than 0.81, p less than 0.05). In four patients who remained deeply comatose for 17 to 25 days, the hypothyroidism and hypogonadism persisted. In six patients who regained consciousness, both endocrine defects improved partially or completely. Injection of 1) thyrotrophic-releasing hormone and 2) gonadotrophic-releasing hormone elicited normal or supernormal increases in plasma concentrations of 1) TSH, and 2) LH and FSH, reduced, respectively, suggesting a suprahypophyseal deficiency. These observations demonstrate that suprahypophyseal hypothryoidism and hypogonadism may occur regularly in patients with traumatic coma lasting longer than 2 weeks.", "contents": "Hypothalamic hypothyroidism and hypogonadism in prolonged traumatic coma. Prolonged coma afterhead trauma is associated with depletion of 3', 5' cyclic adenosine monophosphate (cAMP) in the cerebrospinal fluid (CSF). Because cAMP has previously been implicated in neurorendocrine secretion, this study examines the pituitay-hypothalamic function in 15 adult male patients (to exclude the effects of puberty and menses) with traumatic coma lasting longer than 2 weeks. Ventricular CSF cAMP was measured at 2- to 4-day intervals for 10 to 25 days. Simultaneously, plasma hormone concentrations were also determined. In all 15 cases, CSF cAMP and plasma levels of thyroid-stimulating hormone (TSH), thyroxine (T4), free T4, triiodothyronine (T3), luteinzing hormone (LH), follicle-stimulating hormone (FSH), and testerone became subnormal. In 11 patients whose level of consciousness fluctuated, the reduction in plasma T4 and testerone were proportional to both severity of coma ( r greater than 0.81, p less than 0.05) and depletion of CSF cAMP (r greater than 0.81, p less than 0.05). In four patients who remained deeply comatose for 17 to 25 days, the hypothyroidism and hypogonadism persisted. In six patients who regained consciousness, both endocrine defects improved partially or completely. Injection of 1) thyrotrophic-releasing hormone and 2) gonadotrophic-releasing hormone elicited normal or supernormal increases in plasma concentrations of 1) TSH, and 2) LH and FSH, reduced, respectively, suggesting a suprahypophyseal deficiency. These observations demonstrate that suprahypophyseal hypothryoidism and hypogonadism may occur regularly in patients with traumatic coma lasting longer than 2 weeks."}
{"id": "PMID:213544", "title": "The effect of vitamin D3 and dietary calcium level on the cadmium-induced morphological and biochemical changes in rat intestinal mucosa.", "content": "The effect of vitamin D3 and dietary calcium level on the cadmium-induced changes was observed in the duodena of rats raised on various diets differing in vitamin D and calcium levels. Observation with scanning electron microscopy revealed that vitamin D and dietary calcium were required for normal intestinal villi and microvilli formation. The damaged cells were observed in the intestinal villi of cadmium-exposed rats. Furthermore, dietary cadmium reduced the enzyme activities in microvilli. Especially, alkaline phosphatase activity was reduced in the cadmium-exposed groups, even though it was still responsive to vitamin D3. These effects with cadmium were modulated by vitamin D3 and dietary calcium level. That is, in the presence of vitamin D3 and calcium, the effect of cadmium on intestinal villi and microvilli was reduced.", "contents": "The effect of vitamin D3 and dietary calcium level on the cadmium-induced morphological and biochemical changes in rat intestinal mucosa. The effect of vitamin D3 and dietary calcium level on the cadmium-induced changes was observed in the duodena of rats raised on various diets differing in vitamin D and calcium levels. Observation with scanning electron microscopy revealed that vitamin D and dietary calcium were required for normal intestinal villi and microvilli formation. The damaged cells were observed in the intestinal villi of cadmium-exposed rats. Furthermore, dietary cadmium reduced the enzyme activities in microvilli. Especially, alkaline phosphatase activity was reduced in the cadmium-exposed groups, even though it was still responsive to vitamin D3. These effects with cadmium were modulated by vitamin D3 and dietary calcium level. That is, in the presence of vitamin D3 and calcium, the effect of cadmium on intestinal villi and microvilli was reduced."}
{"id": "PMID:213546", "title": "Wear of combinations of acrylic resin and porcelain, on an abrasion testing machine.", "content": "Wear tests of various combinations of acrylic resin and porcelain were made using a machine which was designed to test materials under conditions similar to those of masticatory function by simulating the loads, sliding distances, and contact times encountered in the human masticatory cycle. The results showed that the amount of wear of the two materials worn in combination depended on the nature of the surrounding medium and on the surface roughness of the opposing material. Acrylic resin showed good wear resistance provided no third party abrasive or opposing hard, rough surface was present. When a mild abrasive was incorporated in the system, the acrylic resin vs acrylic resin combination wore almost seven times more than porcelain vs porcelain. Clinical experience would suggest that this is a reasonably sound order of wear.", "contents": "Wear of combinations of acrylic resin and porcelain, on an abrasion testing machine. Wear tests of various combinations of acrylic resin and porcelain were made using a machine which was designed to test materials under conditions similar to those of masticatory function by simulating the loads, sliding distances, and contact times encountered in the human masticatory cycle. The results showed that the amount of wear of the two materials worn in combination depended on the nature of the surrounding medium and on the surface roughness of the opposing material. Acrylic resin showed good wear resistance provided no third party abrasive or opposing hard, rough surface was present. When a mild abrasive was incorporated in the system, the acrylic resin vs acrylic resin combination wore almost seven times more than porcelain vs porcelain. Clinical experience would suggest that this is a reasonably sound order of wear."}
{"id": "PMID:213548", "title": "Urinary phosphate and cyclic AMP excretion following citrate-induced hypocalcemic stimulation of the neonatal parathyroid glands.", "content": "Sixteen neonates, ranging in gestational age from 27 to 41 weeks and in postnatal age from birth to 8 days, were evaluated for their renal response to an endogenous PTH stimulus in 22 separate experiments. The PTH stimulus was generated by the decreased serum ionized Ca that accompanies exchange transfusion with citrated blood. The neonates increased their serum PTH from 95.8 +/- 13.1 to 133.9 +/- 15.4 microliterEq/ml (mean +/- SEM) during the transfusion, while increasing their urinary cAMP from 0.77 +/- 0.11 to 1.45 +/- 0.22 nmol/ml, and their urinary P from 12.9 +/- 2.6 to 30.6 +/- 6.1 mg/dl in the four hours following the exchange transfusion. This response was not related to postnatal or gestational age. We speculate that lack of renal responsiveness to PTH does not play a major role in the pathogenesis of early neonatal hypocalcemia.", "contents": "Urinary phosphate and cyclic AMP excretion following citrate-induced hypocalcemic stimulation of the neonatal parathyroid glands. Sixteen neonates, ranging in gestational age from 27 to 41 weeks and in postnatal age from birth to 8 days, were evaluated for their renal response to an endogenous PTH stimulus in 22 separate experiments. The PTH stimulus was generated by the decreased serum ionized Ca that accompanies exchange transfusion with citrated blood. The neonates increased their serum PTH from 95.8 +/- 13.1 to 133.9 +/- 15.4 microliterEq/ml (mean +/- SEM) during the transfusion, while increasing their urinary cAMP from 0.77 +/- 0.11 to 1.45 +/- 0.22 nmol/ml, and their urinary P from 12.9 +/- 2.6 to 30.6 +/- 6.1 mg/dl in the four hours following the exchange transfusion. This response was not related to postnatal or gestational age. We speculate that lack of renal responsiveness to PTH does not play a major role in the pathogenesis of early neonatal hypocalcemia."}
{"id": "PMID:213549", "title": "Peripheral median nerve damage secondary to brachial arterial blood gas sampling.", "content": "Examination at 18 months post-term of 139 infants of birth weight less than or equal to 1,500 gm revealed 18 instances (13%) of persistent median nerve damage. All affected infants had received frequent percutaneous brachial artery punctures as neonates. Block sections of the cubital fossa done at autopsy on 12 randomly selected very low-birth-weight infants showed perineural hemorrhage, and Wallerian degeneration or traumatic neuroma of the median nerve in eight patients. It is recommended that brachial artery punctures be avoided whenever possible in the neonatal period.", "contents": "Peripheral median nerve damage secondary to brachial arterial blood gas sampling. Examination at 18 months post-term of 139 infants of birth weight less than or equal to 1,500 gm revealed 18 instances (13%) of persistent median nerve damage. All affected infants had received frequent percutaneous brachial artery punctures as neonates. Block sections of the cubital fossa done at autopsy on 12 randomly selected very low-birth-weight infants showed perineural hemorrhage, and Wallerian degeneration or traumatic neuroma of the median nerve in eight patients. It is recommended that brachial artery punctures be avoided whenever possible in the neonatal period."}
{"id": "PMID:213553", "title": "Species differences in sodium-potassium adenosine triphosphatase activity in the smooth muscle of the guinea-pig and rat vas deferens.", "content": "The acitvities of sodium-potassium-activated adenosine triphosphatase (Na+,K+-activated ATPase) and ouabain-inhibited, sodium-potassium-activated adensoine triphosphatase (Na+,K+-ATPase) in subcellular fractions of guinea-pig and rat vasa deferentia were compared to determine whether the ineffectiveness of ouabain and reduced extracellular potassium in the rat vas deferens observed in the preceding paper occurs because of a relatively low level of Na+,K+-ATPase and/or an insensitivity to ouabain. The results indicate that the specific and total activities of Na+,K+-activated ATPase and Na+,K+-ATPase (i.e., the transport enzyme) in the individual subcellular fractions and in the tissue were higher in the vas deferens of the rat than in the guinea pig. The percentage of inhibition of Na+,K+-activated activity by ouabain (8 x 10(-5) M) varied in the subcellular fractions; it was higher in the guinea-pig (range 31--87%) than in the rat (nonsignificant effect to 40%). A greater percentage of total Na+K+- activated ATPase activity was inhibited in the vas deferens of the guinea pig (56%) than the rat (30%). Differences in the effects of lowered extracellular potassium concentration or ouabain on resting membrane potential (preceding paper) are apparently unrelated to the amount of transport enzyme in the vasa deferentia or the two species, or to its relative sensitivity to ouabain.", "contents": "Species differences in sodium-potassium adenosine triphosphatase activity in the smooth muscle of the guinea-pig and rat vas deferens. The acitvities of sodium-potassium-activated adenosine triphosphatase (Na+,K+-activated ATPase) and ouabain-inhibited, sodium-potassium-activated adensoine triphosphatase (Na+,K+-ATPase) in subcellular fractions of guinea-pig and rat vasa deferentia were compared to determine whether the ineffectiveness of ouabain and reduced extracellular potassium in the rat vas deferens observed in the preceding paper occurs because of a relatively low level of Na+,K+-ATPase and/or an insensitivity to ouabain. The results indicate that the specific and total activities of Na+,K+-activated ATPase and Na+,K+-ATPase (i.e., the transport enzyme) in the individual subcellular fractions and in the tissue were higher in the vas deferens of the rat than in the guinea pig. The percentage of inhibition of Na+,K+-activated activity by ouabain (8 x 10(-5) M) varied in the subcellular fractions; it was higher in the guinea-pig (range 31--87%) than in the rat (nonsignificant effect to 40%). A greater percentage of total Na+K+- activated ATPase activity was inhibited in the vas deferens of the guinea pig (56%) than the rat (30%). Differences in the effects of lowered extracellular potassium concentration or ouabain on resting membrane potential (preceding paper) are apparently unrelated to the amount of transport enzyme in the vasa deferentia or the two species, or to its relative sensitivity to ouabain."}
{"id": "PMID:213554", "title": "Clonidine and related imidazolines are postsynaptic alpha adrenergic antagonists in dispersed rat parotid cells.", "content": "Alpha adrenergic stimulation elicits a rapid release of K+ from dispersed rat parotid cells. Surprisingly neither clonidine, oxymetazoline, naphazoline, ST 600 nor ST 91 elicited K+ release from parotid cells at concentrations up to 100 micrometer. By contrast, these agents were able to block epinephrine-stimulated K+ release with the relative potencies: oxymetazoline more than naphazoline more than clonidine more than ST 600 more than ST 91. [3H]-Dihydroergocryptine (DHE) binds to sites on parotid membranes and intact dispersed cells with the characteristics of alpha adrenergic membrane receptors. The ability of these imidazolines to displace [3H]DHE binding from parotid membranes correlated with their potencies as alpha adrenergic antagonists in the dispersed cells. Although clonidine, oxymetazolin and naphazoline are agonists in other peripheral alpha adrenergic receptors, they are antagonists in the parotid. This observation explains the most common side-effect of clonidine administration, dry mouth, and is consistent with the proposition that different groups of alpha adrenergic receptors exist in mammalian tissues. These data also suggest that the central actions of clonidine must be interpreted with caution since alpha adrenergic receptors similar to those in the parotid may be present in brain.", "contents": "Clonidine and related imidazolines are postsynaptic alpha adrenergic antagonists in dispersed rat parotid cells. Alpha adrenergic stimulation elicits a rapid release of K+ from dispersed rat parotid cells. Surprisingly neither clonidine, oxymetazoline, naphazoline, ST 600 nor ST 91 elicited K+ release from parotid cells at concentrations up to 100 micrometer. By contrast, these agents were able to block epinephrine-stimulated K+ release with the relative potencies: oxymetazoline more than naphazoline more than clonidine more than ST 600 more than ST 91. [3H]-Dihydroergocryptine (DHE) binds to sites on parotid membranes and intact dispersed cells with the characteristics of alpha adrenergic membrane receptors. The ability of these imidazolines to displace [3H]DHE binding from parotid membranes correlated with their potencies as alpha adrenergic antagonists in the dispersed cells. Although clonidine, oxymetazolin and naphazoline are agonists in other peripheral alpha adrenergic receptors, they are antagonists in the parotid. This observation explains the most common side-effect of clonidine administration, dry mouth, and is consistent with the proposition that different groups of alpha adrenergic receptors exist in mammalian tissues. These data also suggest that the central actions of clonidine must be interpreted with caution since alpha adrenergic receptors similar to those in the parotid may be present in brain."}
{"id": "PMID:213555", "title": "Contribution of adrenergic and \"purinergic\" neurotransmission to contraction in rabbit detrusor.", "content": "In the presence of propranolol, norepinephrine produced an alpha adrenoceptor mediated contraction in isolated rabbit detrusor. Phenoxybenzamine (3.3 x 10(-8) M) antagonized this response but failed to affect the contraction produced by field stimulation either in normal or in hemicholinium-3-treated tissue. Higher concentrations of phenoxybenzamine were antagonistic to carbachol. Electrically induced contractions were also unaffected by guanethidine (1 x 10(-4) M) in vitro. Reserpine pretreatment produced no change in the contractile response although the tissue was depleted of catecholamine fluorescence on histology. It is concluded that adrenergic neurotransmission does not account for noncholinergic excitatory neurotransmission in rabbit detrusor. In rabbit detrusor adenosine 5'-triphosphate (ATP) produced a transient contraction which was not antagonized by tetrodotoxin (1 x 10(-7) M), atropine (4 x 10(-7) M) or phenoxybenzamine (3.3 x 10(-7) M). Adenosine, adenine phosphate and adenosine 5'-monophosphate had little or no effect, while sodium tripolyphosphate and adenosine 5'-diphosphate produced a smaller response than ATP. Dipyridamole (1 x 10(-8)-1 x 10(-5) M) did not unmask a response to adenosine and did not potentiate the response to ATP or field stimulation. Theophylline (5 x 10(-5) M) and 2, 2'-pyridylisatogen (PIT) (1 X 10(-5) M) depressed responses to ATP without antagonizing those to carbachol. At these doses, theophylline and 2, 2'-pyridylisatogen also antagonized the electrically induced contraction. Desensitization with ATP (1.5 X 10(-3) M for 30 min) selectively depressed responses to ATP but not to carbachol, and also depressed the response to field stimulation, particularly at frequencies of 10 Hz and lower. It is at these frequences that the noncholinergic component of the contractile response is most significant. Combination of the desensitization procedure with atropine produced an additive effect, suggesting that the two mechanisms affected are independent. Combination of the desensitization procedure with hemicholinium-3 produced less than an additive effect, suggesting an interference between the two treatments. It is concluded that ATP plays a role in the noncholinergic component of excitatory neurotransmission in rabbit detrusor.", "contents": "Contribution of adrenergic and \"purinergic\" neurotransmission to contraction in rabbit detrusor. In the presence of propranolol, norepinephrine produced an alpha adrenoceptor mediated contraction in isolated rabbit detrusor. Phenoxybenzamine (3.3 x 10(-8) M) antagonized this response but failed to affect the contraction produced by field stimulation either in normal or in hemicholinium-3-treated tissue. Higher concentrations of phenoxybenzamine were antagonistic to carbachol. Electrically induced contractions were also unaffected by guanethidine (1 x 10(-4) M) in vitro. Reserpine pretreatment produced no change in the contractile response although the tissue was depleted of catecholamine fluorescence on histology. It is concluded that adrenergic neurotransmission does not account for noncholinergic excitatory neurotransmission in rabbit detrusor. In rabbit detrusor adenosine 5'-triphosphate (ATP) produced a transient contraction which was not antagonized by tetrodotoxin (1 x 10(-7) M), atropine (4 x 10(-7) M) or phenoxybenzamine (3.3 x 10(-7) M). Adenosine, adenine phosphate and adenosine 5'-monophosphate had little or no effect, while sodium tripolyphosphate and adenosine 5'-diphosphate produced a smaller response than ATP. Dipyridamole (1 x 10(-8)-1 x 10(-5) M) did not unmask a response to adenosine and did not potentiate the response to ATP or field stimulation. Theophylline (5 x 10(-5) M) and 2, 2'-pyridylisatogen (PIT) (1 X 10(-5) M) depressed responses to ATP without antagonizing those to carbachol. At these doses, theophylline and 2, 2'-pyridylisatogen also antagonized the electrically induced contraction. Desensitization with ATP (1.5 X 10(-3) M for 30 min) selectively depressed responses to ATP but not to carbachol, and also depressed the response to field stimulation, particularly at frequencies of 10 Hz and lower. It is at these frequences that the noncholinergic component of the contractile response is most significant. Combination of the desensitization procedure with atropine produced an additive effect, suggesting that the two mechanisms affected are independent. Combination of the desensitization procedure with hemicholinium-3 produced less than an additive effect, suggesting an interference between the two treatments. It is concluded that ATP plays a role in the noncholinergic component of excitatory neurotransmission in rabbit detrusor."}
{"id": "PMID:213556", "title": "Presynaptic modulation of beta adrenergic receptors in rat cerebral cortex after treatment with antidepressants.", "content": "Treatment with desmethylimipramine (DMI), a tricyclic antidepressant, for 7 to 21 days resulted in a 35 to 45% decrease in the accumulation of adenosine cyclic 3':5'-monophosphate (cAMP) in response to a maximally effective concentration of (-)-isoproterenol (ISO) in rat cerebral cortical slices. The EC50 for ISO-stimulated cAMP accumulation was not affected by DMI administration. The diminution in responsiveness to catecholamines was accompanied by a 35 to 40% decrease in the density of beta adrenergic receptors as measured by the binding of [125I]iodohydroxybenzylpindolol. Decreases in ISO-sensitive cAMP accumulation and in beta adrenergic receptor density were temporally correlated, maximal decreases being observed within 5 to 7 days. Within 7 days after cessation of chronic DMI treatment ISO-stimulated cAMP accumulation and beta adrenergic receptor density returned to normal. The role of presynaptic nerve terminals in mediating these phenomena was also investigated. Treatment of newborn rats with 6--hydroxydopamine inhibited the development of noradrenergic nerve terminals in the cerebral cortex and blocked the effects of DMI on cortical cAMP accumulation and on beta adrenergic receptor density. The administration of the beta adrenergic receptor antagonist propranolol led to increases in maximal ISO-stimulated cAMP accumulations and beta adrenergic receptor density in the rat cerebral cortex. This increase was not affected by the simultaneous administration of propranolol and DMI. Thus, the effect of DMI appears to be mediated through an action of norepinephrine at beta adrenergic receptors. Chronic treatment with two other clinically effective antidepressants, pargyline and iprindole, led to effects similar to those observed with DMI administration. Pretreatment of neonates with 6-hydroxydopamine blocked the effect of iprindole on beta adrenergic receptors. Preincubation of cortical membranes with guanosinetriphosphate before determination of the density of beta adrenergic receptors had no effect on the decreased number of receptors had no effect on the decreased number of receptors seen in DMI-treated animals. These experiments suggest that antidepressants, acting presynaptically, increase the concentration of transmitter at noradrenergic synapses and induce a compensatory decrease in the density of beta adrenergic receptors.", "contents": "Presynaptic modulation of beta adrenergic receptors in rat cerebral cortex after treatment with antidepressants. Treatment with desmethylimipramine (DMI), a tricyclic antidepressant, for 7 to 21 days resulted in a 35 to 45% decrease in the accumulation of adenosine cyclic 3':5'-monophosphate (cAMP) in response to a maximally effective concentration of (-)-isoproterenol (ISO) in rat cerebral cortical slices. The EC50 for ISO-stimulated cAMP accumulation was not affected by DMI administration. The diminution in responsiveness to catecholamines was accompanied by a 35 to 40% decrease in the density of beta adrenergic receptors as measured by the binding of [125I]iodohydroxybenzylpindolol. Decreases in ISO-sensitive cAMP accumulation and in beta adrenergic receptor density were temporally correlated, maximal decreases being observed within 5 to 7 days. Within 7 days after cessation of chronic DMI treatment ISO-stimulated cAMP accumulation and beta adrenergic receptor density returned to normal. The role of presynaptic nerve terminals in mediating these phenomena was also investigated. Treatment of newborn rats with 6--hydroxydopamine inhibited the development of noradrenergic nerve terminals in the cerebral cortex and blocked the effects of DMI on cortical cAMP accumulation and on beta adrenergic receptor density. The administration of the beta adrenergic receptor antagonist propranolol led to increases in maximal ISO-stimulated cAMP accumulations and beta adrenergic receptor density in the rat cerebral cortex. This increase was not affected by the simultaneous administration of propranolol and DMI. Thus, the effect of DMI appears to be mediated through an action of norepinephrine at beta adrenergic receptors. Chronic treatment with two other clinically effective antidepressants, pargyline and iprindole, led to effects similar to those observed with DMI administration. Pretreatment of neonates with 6-hydroxydopamine blocked the effect of iprindole on beta adrenergic receptors. Preincubation of cortical membranes with guanosinetriphosphate before determination of the density of beta adrenergic receptors had no effect on the decreased number of receptors had no effect on the decreased number of receptors seen in DMI-treated animals. These experiments suggest that antidepressants, acting presynaptically, increase the concentration of transmitter at noradrenergic synapses and induce a compensatory decrease in the density of beta adrenergic receptors."}
{"id": "PMID:213557", "title": "Evidence for the involvement of cerebroside sulfate in opiate receptor binding: Studies with Azure A and jimpy mutant mice.", "content": "The role of cerebroside sulfate in opiate action and binding was studied by examining the effect of decreasing the availability of the glycolipid in vivo on morphine analgetic activity and receptor affinity. Available cerebroside sites were decreased either by injecting Azure A at a dose with selective high affinity for sulfo-lipids, or by using \"jimpy\" mice, a genetic leukodystropic mutant mouse with a deficiency in brain sulfatides. Injections of Azure A (4.4 MG/KG) intracerebroventricularly produced a 2-fold increase in the AD50 of morphine (tail-flick test) within 2 hr. The genetic mutation also resulted in a decreased sensitivity to morphine; the morphine AD50 was 6- to 11-fold higher in jimpy mice than in their normal littermates. Azure A produced a dose-dependent inhibition of opiate binding to synaptosomal plasma membranes. There was 85% inhibition of [3H]morphine binding with 0.2 micrometer Azure A, and 40% inhibition of [3H]naloxone binding with 5 micrometer Azure A. The inhibition of morphine binding was competitive and was demonstrated to be different from that elicited by Na+. Synaptic membranes from jimpy mice exhibited a decrease in number of binding sites for morphine. Binding of Azure A to cerebroside sulfate, associated with or in the proximity of the receptor sites, was suggested by the fact that in the presence of 0.2 micrometer Azure A, no inhibition of [3H]morphine binding to synaptosomal plasma membranes of jimpy mice could be demonstrated whereas 31% inh-bition was observed in membranes from control littermates. Based on the findings, it is concluded that cerebroside sulfate strategically located may have a role in binding morphine and mediating its effects.", "contents": "Evidence for the involvement of cerebroside sulfate in opiate receptor binding: Studies with Azure A and jimpy mutant mice. The role of cerebroside sulfate in opiate action and binding was studied by examining the effect of decreasing the availability of the glycolipid in vivo on morphine analgetic activity and receptor affinity. Available cerebroside sites were decreased either by injecting Azure A at a dose with selective high affinity for sulfo-lipids, or by using \"jimpy\" mice, a genetic leukodystropic mutant mouse with a deficiency in brain sulfatides. Injections of Azure A (4.4 MG/KG) intracerebroventricularly produced a 2-fold increase in the AD50 of morphine (tail-flick test) within 2 hr. The genetic mutation also resulted in a decreased sensitivity to morphine; the morphine AD50 was 6- to 11-fold higher in jimpy mice than in their normal littermates. Azure A produced a dose-dependent inhibition of opiate binding to synaptosomal plasma membranes. There was 85% inhibition of [3H]morphine binding with 0.2 micrometer Azure A, and 40% inhibition of [3H]naloxone binding with 5 micrometer Azure A. The inhibition of morphine binding was competitive and was demonstrated to be different from that elicited by Na+. Synaptic membranes from jimpy mice exhibited a decrease in number of binding sites for morphine. Binding of Azure A to cerebroside sulfate, associated with or in the proximity of the receptor sites, was suggested by the fact that in the presence of 0.2 micrometer Azure A, no inhibition of [3H]morphine binding to synaptosomal plasma membranes of jimpy mice could be demonstrated whereas 31% inh-bition was observed in membranes from control littermates. Based on the findings, it is concluded that cerebroside sulfate strategically located may have a role in binding morphine and mediating its effects."}
{"id": "PMID:213562", "title": "Psychiatric patients' perceptions of their milieu therapy program.", "content": "This study was designed to provide information concerning psychiatric patients' perceptions of their individual treatment program in an inpatient treatment facility with an established therapeutic milieu. The responses of 24 patients aged 16 to 69 years to an 8-item questionnaire, developed and administered by the investigator, constituted the data collected. The 24 patients identified 57 components as part of their treatment programs. Patients with more education mentioned more treatment components than those with less education. Talking with staff members was considered the most helpful treatment component by the most patients, and medication was the most frequently mentioned least helpful treatment component. Six categories were used to organize the data: recreation-physical, recreation-mental, verbal interaction, creature comforts, staff supervision, and diagnostic and medical services. More of the identified treatment components were categorized under verbal interaction than any other category. The second most mentioned category was recreation-physical. As patients listed the most helpful persons during their hospitalization, 36 students and staff members and four other patients were identified. Two psychiatric technicians, a registered nurse, and an occupational therapist were mentioned most often. Patients tended to see persons of their same sex and close to their age as particularly helpful.", "contents": "Psychiatric patients' perceptions of their milieu therapy program. This study was designed to provide information concerning psychiatric patients' perceptions of their individual treatment program in an inpatient treatment facility with an established therapeutic milieu. The responses of 24 patients aged 16 to 69 years to an 8-item questionnaire, developed and administered by the investigator, constituted the data collected. The 24 patients identified 57 components as part of their treatment programs. Patients with more education mentioned more treatment components than those with less education. Talking with staff members was considered the most helpful treatment component by the most patients, and medication was the most frequently mentioned least helpful treatment component. Six categories were used to organize the data: recreation-physical, recreation-mental, verbal interaction, creature comforts, staff supervision, and diagnostic and medical services. More of the identified treatment components were categorized under verbal interaction than any other category. The second most mentioned category was recreation-physical. As patients listed the most helpful persons during their hospitalization, 36 students and staff members and four other patients were identified. Two psychiatric technicians, a registered nurse, and an occupational therapist were mentioned most often. Patients tended to see persons of their same sex and close to their age as particularly helpful."}
{"id": "PMID:213570", "title": "An ecological framework for crisis intervention.", "content": "In summary, the experience of working with children in an institutional setting lends itself to meeting specific learning objectives for the baccalaureate nursing student as well as providing assistance to a child in dealing with a crisis. Utilization of the human ecological approach allows the student to assist the child in a more meaningful way by examining the environmental context (both internal and external) in which his psychic pain is occurring.", "contents": "An ecological framework for crisis intervention. In summary, the experience of working with children in an institutional setting lends itself to meeting specific learning objectives for the baccalaureate nursing student as well as providing assistance to a child in dealing with a crisis. Utilization of the human ecological approach allows the student to assist the child in a more meaningful way by examining the environmental context (both internal and external) in which his psychic pain is occurring."}
{"id": "PMID:213572", "title": "Three assessment tools for family therapy.", "content": "In this paper the authors attempt to utilize existing knowledge of the family and family therapy in order to develop a universal tool for family analysis. The assessment tools represent a conceptualization of the three phases of family analysis. Using a simplistic guide, such as these assessment tools, should aid the therapist in organizing the overwhelming volume of information that is obtained in a short amount of interviewing time. Again the assessment tools are only as applicable as the family therapist is imaginative and creative.", "contents": "Three assessment tools for family therapy. In this paper the authors attempt to utilize existing knowledge of the family and family therapy in order to develop a universal tool for family analysis. The assessment tools represent a conceptualization of the three phases of family analysis. Using a simplistic guide, such as these assessment tools, should aid the therapist in organizing the overwhelming volume of information that is obtained in a short amount of interviewing time. Again the assessment tools are only as applicable as the family therapist is imaginative and creative."}
{"id": "PMID:213575", "title": "Clinical judgment: an ethical issue.", "content": "In conclusion, the position of this paper maintains that clinical judgment is a viable, ethical issue of the highest order. Clinical judgment involves the personal orientation, the ethical framework of the one making the decision. Whatever judgment is ultimately made carries with it the burden of the maker's personal ethical approach to life, to the nature of man and finally his approach to the world at large. Clinical judgment is inseparable from ethics. It is further maintained that there must be more research into the areas of clinical judgment in relation to psychiatric nursing research. Clinical specialists, in particular, will be called on to make increasingly complex judgments. They must have a valid method to assist in the formulation, testing and analysis of their decisions. A model must be developed that assists the decision maker in: 1. Objectively identifying and specifying stimul; 2. Controlling and regulating the conditions of the judgment-making-process, intrinsic as well as extrinsic; and 3. Defining and standardizing the conditions of reporting.", "contents": "Clinical judgment: an ethical issue. In conclusion, the position of this paper maintains that clinical judgment is a viable, ethical issue of the highest order. Clinical judgment involves the personal orientation, the ethical framework of the one making the decision. Whatever judgment is ultimately made carries with it the burden of the maker's personal ethical approach to life, to the nature of man and finally his approach to the world at large. Clinical judgment is inseparable from ethics. It is further maintained that there must be more research into the areas of clinical judgment in relation to psychiatric nursing research. Clinical specialists, in particular, will be called on to make increasingly complex judgments. They must have a valid method to assist in the formulation, testing and analysis of their decisions. A model must be developed that assists the decision maker in: 1. Objectively identifying and specifying stimul; 2. Controlling and regulating the conditions of the judgment-making-process, intrinsic as well as extrinsic; and 3. Defining and standardizing the conditions of reporting."}
{"id": "PMID:213579", "title": "Liaison nursing.", "content": "In reviewing my efforts to clarify the role of the nurse clinician as a psychiatric consultant in a hospital setting, I came away with many impressions. Inherent in my search was a desire to experiment with various means of providing nursing service and much of my time was spent examining the collaborative aspects of the nursing role that would add greater depth to patient care. This involved role experimentation and allowed me the opportunity to develop my role within the context of the guidelines of community organization and consultation in a hospital setting. Although much of the time I found that the liaison role has been aimed at the supportive level, I have also discovered that as I developed security in the role wherein I could function in new and more independent ways--the parameters of the role expanded. Whereas initially I envisioned working only with nursing staff, I have found myself collaborating with many disciplines and many levels of care givers and I have also been able to function collaboratively with other psychiatric liaison team members. Thus, at this time I see the liaison nurse functioning basically as a coordinator, who, at any time, may assume one or more of the following roles: 1) Integrator; 2) Provider of direct services; 3) Educator and consultant; 4) Change agent.", "contents": "Liaison nursing. In reviewing my efforts to clarify the role of the nurse clinician as a psychiatric consultant in a hospital setting, I came away with many impressions. Inherent in my search was a desire to experiment with various means of providing nursing service and much of my time was spent examining the collaborative aspects of the nursing role that would add greater depth to patient care. This involved role experimentation and allowed me the opportunity to develop my role within the context of the guidelines of community organization and consultation in a hospital setting. Although much of the time I found that the liaison role has been aimed at the supportive level, I have also discovered that as I developed security in the role wherein I could function in new and more independent ways--the parameters of the role expanded. Whereas initially I envisioned working only with nursing staff, I have found myself collaborating with many disciplines and many levels of care givers and I have also been able to function collaboratively with other psychiatric liaison team members. Thus, at this time I see the liaison nurse functioning basically as a coordinator, who, at any time, may assume one or more of the following roles: 1) Integrator; 2) Provider of direct services; 3) Educator and consultant; 4) Change agent."}
{"id": "PMID:213581", "title": "Partners in therapy: using the co-therapists' relationship in a group.", "content": "While this article has been necessarily narrow in scope in order to develop the theme of gives some direction toward other related aspects: the process of relationship development was alluded to but not presented; the transference phenomenon has been the subject of numerous psychiatric articles and could be further explored in the co-therapy situation; and the value of preservation of group interactions on recording tape or videotape for analysis by co-therapists could be researched. The final implication that should be left with the reader concerns the broader application of the co-therapy relationship: in what other psychotherapeutic areas, such as individual therapy or therapy with disturbed children, could the conjointly-developed relationship between two or more interdisciplinary therapists utilized expediently and efficaciously? While we are not suggesting that co-therapy is a panacea, we do hope that more thought will be given to the application of interdisciplinary co-therapy in various psychiatric settings and situations.", "contents": "Partners in therapy: using the co-therapists' relationship in a group. While this article has been necessarily narrow in scope in order to develop the theme of gives some direction toward other related aspects: the process of relationship development was alluded to but not presented; the transference phenomenon has been the subject of numerous psychiatric articles and could be further explored in the co-therapy situation; and the value of preservation of group interactions on recording tape or videotape for analysis by co-therapists could be researched. The final implication that should be left with the reader concerns the broader application of the co-therapy relationship: in what other psychotherapeutic areas, such as individual therapy or therapy with disturbed children, could the conjointly-developed relationship between two or more interdisciplinary therapists utilized expediently and efficaciously? While we are not suggesting that co-therapy is a panacea, we do hope that more thought will be given to the application of interdisciplinary co-therapy in various psychiatric settings and situations."}
{"id": "PMID:213583", "title": "Applying Yalom's principles to crisis work...some intriguing results.", "content": "In this paper, the writer has shared some of the results of an innovative eight- to sixteen-week, open-ended crisis group developed at the Community Mental Health Center at Strong Memorial Hospital. The group has been running for over a year and a half. Some of the significant findings were that process interventions can be creatively used in a modified manner to enhance the group interaction, while maintaining the crisis-oriented focus. There were two dimensions of process commentary described, the sense data material of an individual, interpersonal nature, and the mass group interventions with a broader, group development focus. In addition, the secondary function of the group, which was to serve as an assessment tool for an individual's capabilities in long-term group work, proved to be reliable for eighteen out of the twenty members, eventually referred to other groups. A theoretical framework, based on Yalom's work, as well as the writer's synthesis of previous crisis group theory, was outlined. Two clinical illustrations were described, using the paradigm. In closing, the writer wishes to validate the impression that crisis group work is indeed an exciting, clinical adventure. Each week the gestalt of the group varies, so that the crisis therapist must remain a versatile strategist and sensitive role model of communication theory. The interweaving of process issues with more concrete, content-focused group work provides the members with an in-depth, sharply practical interpersonal arena for growth.", "contents": "Applying Yalom's principles to crisis work...some intriguing results. In this paper, the writer has shared some of the results of an innovative eight- to sixteen-week, open-ended crisis group developed at the Community Mental Health Center at Strong Memorial Hospital. The group has been running for over a year and a half. Some of the significant findings were that process interventions can be creatively used in a modified manner to enhance the group interaction, while maintaining the crisis-oriented focus. There were two dimensions of process commentary described, the sense data material of an individual, interpersonal nature, and the mass group interventions with a broader, group development focus. In addition, the secondary function of the group, which was to serve as an assessment tool for an individual's capabilities in long-term group work, proved to be reliable for eighteen out of the twenty members, eventually referred to other groups. A theoretical framework, based on Yalom's work, as well as the writer's synthesis of previous crisis group theory, was outlined. Two clinical illustrations were described, using the paradigm. In closing, the writer wishes to validate the impression that crisis group work is indeed an exciting, clinical adventure. Each week the gestalt of the group varies, so that the crisis therapist must remain a versatile strategist and sensitive role model of communication theory. The interweaving of process issues with more concrete, content-focused group work provides the members with an in-depth, sharply practical interpersonal arena for growth."}
{"id": "PMID:213597", "title": "Mental health consultation in a home care agency.", "content": "A mental health nurse, educationally and clinically prepared as a specialist, can be effectively utilized as a consultant to aid nurse generalists in assessment and intervention of patients in a home health care agency. An individual staff nurse consulting with the specialist or a group of nurses provides the setting for consultant led case discussions. Consultation is a highly efficient use of specialist's knowledge and skills in health care delivery, and also provides learning opportunities for staff.", "contents": "Mental health consultation in a home care agency. A mental health nurse, educationally and clinically prepared as a specialist, can be effectively utilized as a consultant to aid nurse generalists in assessment and intervention of patients in a home health care agency. An individual staff nurse consulting with the specialist or a group of nurses provides the setting for consultant led case discussions. Consultation is a highly efficient use of specialist's knowledge and skills in health care delivery, and also provides learning opportunities for staff."}
{"id": "PMID:213598", "title": "The role of operations research and systems analysis in holding down the costs of hospitals and clinics.", "content": "In the past, medical care facilities have concentrated primarily on professional clinical evaluation. With the cost of treatment rising rapidly, it is becoming increasingly important to critically review and analyze our delivery systems so that scarce resources can be used optimally. In this paper the applications of operations research (O.R.) and systems analysis techniques that have been employed successfully in private industry are explored to find ways to improve clinical operations and hold costs down.", "contents": "The role of operations research and systems analysis in holding down the costs of hospitals and clinics. In the past, medical care facilities have concentrated primarily on professional clinical evaluation. With the cost of treatment rising rapidly, it is becoming increasingly important to critically review and analyze our delivery systems so that scarce resources can be used optimally. In this paper the applications of operations research (O.R.) and systems analysis techniques that have been employed successfully in private industry are explored to find ways to improve clinical operations and hold costs down."}
{"id": "PMID:213601", "title": "Studies on the susceptibility of the mouse preimplantation embryo to infection with cytomegalovirus.", "content": "Intact and zona-free mouse preimplantation embryos were exposed to murine cytomegalovirus in vitro at various stages of development. The embryos developed normally to the blastocyst stage, and there was no evidence of embryonic infection. Intraperitoneal inoculation of female mice with this virus produced an acute generalized infection, and embryonic development was retarded in vivo. The embryos themselves were not productively infected, and they developed into apparently normal fetuses when transferred to uninfected mice.", "contents": "Studies on the susceptibility of the mouse preimplantation embryo to infection with cytomegalovirus. Intact and zona-free mouse preimplantation embryos were exposed to murine cytomegalovirus in vitro at various stages of development. The embryos developed normally to the blastocyst stage, and there was no evidence of embryonic infection. Intraperitoneal inoculation of female mice with this virus produced an acute generalized infection, and embryonic development was retarded in vivo. The embryos themselves were not productively infected, and they developed into apparently normal fetuses when transferred to uninfected mice."}
{"id": "PMID:213602", "title": "Luteal function in sows after unilateral infusion of PGF-2alpha into the anterior uterine vein on different days of the oestrous cycle.", "content": "Prostaglandin F-2alpha (1.5 mg over 10 h) was infused into the anterior uterine vein of pigs on Days 6, 8, 10, 12, 14 and 15 of the oestrous cycle. At each stage of the cycle PGF-2alpha suppressed luteal function although the fall in progesterone secretion was much greater and statistically significant when the infusion was performed on Days 12, 14 and 15 of the cycle than on Days 6, 8 and 10. The concentrations of cAMP was depressed on Days 15 and 17 and fatty degeneration of luteal cells on Days 6--8 or 14 was more pronounced in the ovary ipsilateral to the PGF-2alpha infusion than in the contralateral ovary. The results are compatible with the local perfusion of PGF-2alpha from the anterior uterine vein to the ipsilateral ovary, but a systemic effect was also apparent.", "contents": "Luteal function in sows after unilateral infusion of PGF-2alpha into the anterior uterine vein on different days of the oestrous cycle. Prostaglandin F-2alpha (1.5 mg over 10 h) was infused into the anterior uterine vein of pigs on Days 6, 8, 10, 12, 14 and 15 of the oestrous cycle. At each stage of the cycle PGF-2alpha suppressed luteal function although the fall in progesterone secretion was much greater and statistically significant when the infusion was performed on Days 12, 14 and 15 of the cycle than on Days 6, 8 and 10. The concentrations of cAMP was depressed on Days 15 and 17 and fatty degeneration of luteal cells on Days 6--8 or 14 was more pronounced in the ovary ipsilateral to the PGF-2alpha infusion than in the contralateral ovary. The results are compatible with the local perfusion of PGF-2alpha from the anterior uterine vein to the ipsilateral ovary, but a systemic effect was also apparent."}
{"id": "PMID:213604", "title": "Coxsackievirus in an infant chimpanzee.", "content": "Coxsackie B viruses may cause a severe, often fatal, illness in newborn and infant human subjects. As recorded in this case, infant chimpanzees respond similarly to Coxsackie B-5 virus.", "contents": "Coxsackievirus in an infant chimpanzee. Coxsackie B viruses may cause a severe, often fatal, illness in newborn and infant human subjects. As recorded in this case, infant chimpanzees respond similarly to Coxsackie B-5 virus."}
{"id": "PMID:213605", "title": "Slow and rapid responses to CW and pulsed microwave radiation by individual Aplysia pacemakers.", "content": "Specific absorption rates (SARs) of microwave energy that altered firing rates were determined for individual pacemaker neurons in the abdominal ganglion of Aplysia californica. A stripline apparatus provided both for artifact-free recording of transmembrane potentials and for precise determination of the rate of absorption of microwave energy. Exposure for two to three minutes at an SAR of only a few mW/g was capable of changing the firing rate of some pacemakers. Two types of responses were observed. The response that was seen in all neurons developed slowly, reaching a steady state in one to three minutes. The other response was seen in a few neurons and occurred within five seconds from the onset of irradiation. Similar responses were obtained for two microwave frequencies, 1.5 and 2.45 GHz. Pulsed radiation induced rapid changes of firing rate more readily than did CW radiation at the same SAR. A convective heating scheme was used to study the effects of temperature changes on the pacemakers' firing rates. Since all of the responses are not readily explained by general heating of the preparation, alternate mechanisms are suggested for the observed effects.", "contents": "Slow and rapid responses to CW and pulsed microwave radiation by individual Aplysia pacemakers. Specific absorption rates (SARs) of microwave energy that altered firing rates were determined for individual pacemaker neurons in the abdominal ganglion of Aplysia californica. A stripline apparatus provided both for artifact-free recording of transmembrane potentials and for precise determination of the rate of absorption of microwave energy. Exposure for two to three minutes at an SAR of only a few mW/g was capable of changing the firing rate of some pacemakers. Two types of responses were observed. The response that was seen in all neurons developed slowly, reaching a steady state in one to three minutes. The other response was seen in a few neurons and occurred within five seconds from the onset of irradiation. Similar responses were obtained for two microwave frequencies, 1.5 and 2.45 GHz. Pulsed radiation induced rapid changes of firing rate more readily than did CW radiation at the same SAR. A convective heating scheme was used to study the effects of temperature changes on the pacemakers' firing rates. Since all of the responses are not readily explained by general heating of the preparation, alternate mechanisms are suggested for the observed effects."}
{"id": "PMID:213606", "title": "Analysis of the effects of microwave energy on enzymatic activity of lactate dehydrogenase (LDH).", "content": "Interactions between microwave energy (3 GHz) and the enzyme Lactate Dehydrogenase (LDH) have been analyzed by monitoring the enzymatic activity during irradiation in steady-state or dynamic conditions, by irradiating the sample with variable power levels (up to 6 W into the sample) and, finally, by knowing accurately the true specific absorption rate. No permanent or temporary changes can be induced when the energy absorption does not cause a temperature variation. For higher energy values, effects are purely thermal in nature. Furthermore the thermal activation of the reaction velocity, caused by microwave irradiation, is in itself sufficient to give a good fit with the experimental time evolution of the enzymatic reaction.", "contents": "Analysis of the effects of microwave energy on enzymatic activity of lactate dehydrogenase (LDH). Interactions between microwave energy (3 GHz) and the enzyme Lactate Dehydrogenase (LDH) have been analyzed by monitoring the enzymatic activity during irradiation in steady-state or dynamic conditions, by irradiating the sample with variable power levels (up to 6 W into the sample) and, finally, by knowing accurately the true specific absorption rate. No permanent or temporary changes can be induced when the energy absorption does not cause a temperature variation. For higher energy values, effects are purely thermal in nature. Furthermore the thermal activation of the reaction velocity, caused by microwave irradiation, is in itself sufficient to give a good fit with the experimental time evolution of the enzymatic reaction."}
{"id": "PMID:213610", "title": "Development of cell-mediated immunity to Marek's disease tumor cells in chickens inoculated with Marek's disease vaccines.", "content": "Chickens inoculated with herpesvirus of turkeys or with apathogenic or attenuated vaccine strains of Marek's disease virus (MDV) developed a T-cell-mediated immune response to Marek's disease (MD) tumor cells. This immune response was detected in a 4-hour 51Cr-release assay in which effector cells obtained from spleens of vaccinated chickens were reacted with 51Cr-labeled target cells of an MD lymphoblastoid cell line (MSB-1). The cytotoxic effector cells generated by the vaccine viruses had characteristics similar to those noted previously for anti-MSB-1 effector cells generated by MDV. The immune response was specific to MSB-1 cells, because another target cell line (TLT) antigenically unrelated to MSB-1 cells was not lysed by the effector cells nor did the unrelated target cells inhibit the cytotoxicity of effector cells against MSB-1 target in a cold-target inhibition assay. Because MSB-1 cells contain MD tumor-associated surface antigen, we postulated that the immune response detected in the vaccinated chickens may be directed against this antigen and that the antitumor antigen immunity may play a role in the mechanism of vaccine protection against lymphoma development by pathogenic MDV.", "contents": "Development of cell-mediated immunity to Marek's disease tumor cells in chickens inoculated with Marek's disease vaccines. Chickens inoculated with herpesvirus of turkeys or with apathogenic or attenuated vaccine strains of Marek's disease virus (MDV) developed a T-cell-mediated immune response to Marek's disease (MD) tumor cells. This immune response was detected in a 4-hour 51Cr-release assay in which effector cells obtained from spleens of vaccinated chickens were reacted with 51Cr-labeled target cells of an MD lymphoblastoid cell line (MSB-1). The cytotoxic effector cells generated by the vaccine viruses had characteristics similar to those noted previously for anti-MSB-1 effector cells generated by MDV. The immune response was specific to MSB-1 cells, because another target cell line (TLT) antigenically unrelated to MSB-1 cells was not lysed by the effector cells nor did the unrelated target cells inhibit the cytotoxicity of effector cells against MSB-1 target in a cold-target inhibition assay. Because MSB-1 cells contain MD tumor-associated surface antigen, we postulated that the immune response detected in the vaccinated chickens may be directed against this antigen and that the antitumor antigen immunity may play a role in the mechanism of vaccine protection against lymphoma development by pathogenic MDV."}
{"id": "PMID:213611", "title": "Cyclic nucleotide concentrations in 7.12-dimethylbenz[a]anthracene-induced pancreatic cancer in rats.", "content": "Pancreas cancer was induced in noninbred male Holtzman rats by the implantation of beeswax containing 7.12-dimethylbenz[a]anthracene (DMBA) into the \"head\" of the pancreas. The tumors that developed 4--6 months later were examined for their cyclic AMP and cyclic GMP levels. The lesions could be considered in one of two categories according to their cyclic nucleotide contents: lesions with significantly smaller amounts and those with greater amounts, compared with levels measured in the pancreas tissues of the control rats. The existence of two biochemically distinct groups may indicate different growth patterns of the DMBA-induced pancreatic neoplasia.", "contents": "Cyclic nucleotide concentrations in 7.12-dimethylbenz[a]anthracene-induced pancreatic cancer in rats. Pancreas cancer was induced in noninbred male Holtzman rats by the implantation of beeswax containing 7.12-dimethylbenz[a]anthracene (DMBA) into the \"head\" of the pancreas. The tumors that developed 4--6 months later were examined for their cyclic AMP and cyclic GMP levels. The lesions could be considered in one of two categories according to their cyclic nucleotide contents: lesions with significantly smaller amounts and those with greater amounts, compared with levels measured in the pancreas tissues of the control rats. The existence of two biochemically distinct groups may indicate different growth patterns of the DMBA-induced pancreatic neoplasia."}
{"id": "PMID:213613", "title": "Stimulatory effect of immunization on tumor induction by Moloney murine sarcoma virus.", "content": "Adult mice were immunized with varying doses of inactivated Moloney murine leukemia virus (M-MuLV). Eight weeks after immunization, mice were challenged with a dose of Moloney murine sarcoma virus (M-MuSV) that could induce tumors in approximately 50% of normal animals. Mice immunized with high doses of M-MuLV (10(10) particles) had significantly decreased tumor incidences, whereas mice immunized with low doses of M-MuLV (10(2) particles) had significnatly increased tumor incidences compared to those in nonimmunized controls. The stimulatory effect could be abrogated by the irradiation of mice with 450 rads 24 hours prior to M-MuSV challenge, whereas the inhibitory effect was resistant to this irradiation procedure. The results suggested that immunization with virus can either stimulate or inhibit virus-induced tumorigenesis, depending on the dose of virus used for immunization.", "contents": "Stimulatory effect of immunization on tumor induction by Moloney murine sarcoma virus. Adult mice were immunized with varying doses of inactivated Moloney murine leukemia virus (M-MuLV). Eight weeks after immunization, mice were challenged with a dose of Moloney murine sarcoma virus (M-MuSV) that could induce tumors in approximately 50% of normal animals. Mice immunized with high doses of M-MuLV (10(10) particles) had significantly decreased tumor incidences, whereas mice immunized with low doses of M-MuLV (10(2) particles) had significnatly increased tumor incidences compared to those in nonimmunized controls. The stimulatory effect could be abrogated by the irradiation of mice with 450 rads 24 hours prior to M-MuSV challenge, whereas the inhibitory effect was resistant to this irradiation procedure. The results suggested that immunization with virus can either stimulate or inhibit virus-induced tumorigenesis, depending on the dose of virus used for immunization."}
{"id": "PMID:213614", "title": "Expression of RNA of an endogenous replication-defective retrovirus in rat mammary adenocarcinomas induced by 7,12-dimethylbenz[a]anthracene.", "content": "An investigation into the possible relationship between chemical carcinogen induction of rat mammary tumors and the expression of an endogenous retroviral genome was initiated. Mammary tumors were induced in female SD rats with 7,12-dimethylbenz[a]anthracene (DMBA). Tumors, identified histologically as mammary adenocarcinomas, were analyzed for RNA of a replication-defective endogenous retrovirus or RNA of a helper-independent endogenous type C virus. Expression of RNA of the replication-defective virus was detected in mammary tumors weighing 0.2--2.0 g. Larger tumors, for which histologic examination revealed proportionally more fibroblastic tissue than epithelial cells, did not contain comparable concentrations of this viral RNA. RNA homologous to a helper-independent rat type C retrovirus was not detected in tumors of any size. A cell line was established from a primary DMBA-induced mammary adenocarcinoma and appeared similar to the small mammary tumors with respect to endogenous type C viral RNA expression. We discuss possible implications of the expression of endogenous replication-defective viruses for use as markers for the effects of chemical carcinogens.", "contents": "Expression of RNA of an endogenous replication-defective retrovirus in rat mammary adenocarcinomas induced by 7,12-dimethylbenz[a]anthracene. An investigation into the possible relationship between chemical carcinogen induction of rat mammary tumors and the expression of an endogenous retroviral genome was initiated. Mammary tumors were induced in female SD rats with 7,12-dimethylbenz[a]anthracene (DMBA). Tumors, identified histologically as mammary adenocarcinomas, were analyzed for RNA of a replication-defective endogenous retrovirus or RNA of a helper-independent endogenous type C virus. Expression of RNA of the replication-defective virus was detected in mammary tumors weighing 0.2--2.0 g. Larger tumors, for which histologic examination revealed proportionally more fibroblastic tissue than epithelial cells, did not contain comparable concentrations of this viral RNA. RNA homologous to a helper-independent rat type C retrovirus was not detected in tumors of any size. A cell line was established from a primary DMBA-induced mammary adenocarcinoma and appeared similar to the small mammary tumors with respect to endogenous type C viral RNA expression. We discuss possible implications of the expression of endogenous replication-defective viruses for use as markers for the effects of chemical carcinogens."}
{"id": "PMID:213618", "title": "Bilateral Wilms tumors.", "content": "The current management of bilateral Wilms tumor is reviewed and the high incidence of concurrent anomalies with bilateral Wilms tumor is demonstrated in 4 of 5 children. Standardization of management has not been established. Of the 5 patients 3 survived 30 months to 11 years without recurrent tumor. Two had unilateral nephrectomy and partial nephrectomy, while 1 had bilateral nephrectomy and allotransplant. All survivors have had adjunctive chemotherapy and radiotherapy.", "contents": "Bilateral Wilms tumors. The current management of bilateral Wilms tumor is reviewed and the high incidence of concurrent anomalies with bilateral Wilms tumor is demonstrated in 4 of 5 children. Standardization of management has not been established. Of the 5 patients 3 survived 30 months to 11 years without recurrent tumor. Two had unilateral nephrectomy and partial nephrectomy, while 1 had bilateral nephrectomy and allotransplant. All survivors have had adjunctive chemotherapy and radiotherapy."}
{"id": "PMID:213620", "title": "Primary cytomegalovirus and opportunistic infections. Incidence in renal transplant recipients.", "content": "Thirty-five renal allograft recipients were studied concerning the relationship between cytomegalovirus (CMV), herpes simplex virus (HSV), and opportunistic bacterial and fungal infections. The incidence of opportunistic infections was determined for patients whose tests prior to transplantation were seronegative in complement fixation and indirect hemagglutination assays of CMV antibody and for those patients whose tests were seropositive. Among the six seronegative patients with seronegative tests, four (66%) experienced active CMV infection within two months, and four died of Candida or Aspergillus infection within six months after transplantation. Among the 22 patients with seropositive tests, only one (4%) had a fungal infection and it was nonfatal (P less than .05). The increased morbidity and mortality due to fungal and bacterial infections in transplant recipients with seronegative CMV tests appears, therefore, to be related to primary CMV infection rather than to generalized immunodeficiency.", "contents": "Primary cytomegalovirus and opportunistic infections. Incidence in renal transplant recipients. Thirty-five renal allograft recipients were studied concerning the relationship between cytomegalovirus (CMV), herpes simplex virus (HSV), and opportunistic bacterial and fungal infections. The incidence of opportunistic infections was determined for patients whose tests prior to transplantation were seronegative in complement fixation and indirect hemagglutination assays of CMV antibody and for those patients whose tests were seropositive. Among the six seronegative patients with seronegative tests, four (66%) experienced active CMV infection within two months, and four died of Candida or Aspergillus infection within six months after transplantation. Among the 22 patients with seropositive tests, only one (4%) had a fungal infection and it was nonfatal (P less than .05). The increased morbidity and mortality due to fungal and bacterial infections in transplant recipients with seronegative CMV tests appears, therefore, to be related to primary CMV infection rather than to generalized immunodeficiency."}
{"id": "PMID:213622", "title": "Bone marrow sarcoidosis.", "content": "Five patients' bone marrow was involved with sarcoidosis, but their chest roentgenograms were normal. The diagnosis was substantiated by typical histological appearance of noncaseating granulomas in bone marrow, careful exclusion of infectious disease, and follow-up study for three to six years. Angiotensin-converting enzyme levels were elevated in all patients at the time of diagnosis.", "contents": "Bone marrow sarcoidosis. Five patients' bone marrow was involved with sarcoidosis, but their chest roentgenograms were normal. The diagnosis was substantiated by typical histological appearance of noncaseating granulomas in bone marrow, careful exclusion of infectious disease, and follow-up study for three to six years. Angiotensin-converting enzyme levels were elevated in all patients at the time of diagnosis."}
{"id": "PMID:213623", "title": "Serum high density lipoprotein in hemodialysis patients.", "content": "Uremic patients on prolonged maintenance hemodialysis (hemodialysis patients) are at high risk for atherosclerotic cardiovascular complications. To investigate the serum lipoprotein (Lp) abnormalities in hemodialysis patients, high density Lp (HDL) concentration was determined using ultracentrifugal analysis and quantitative immunoelectrophoresis in 23 hemodialysis patients, 8 non-uremic hyperlipidemic subjects, and 12 normal subjects. Immunoreactive HDL as well as HDL-cholesterol (HDL-Ch) in hemodialysis patients was lower significantly than the level in patients with non-uremic hyperlipidemia or normolipidemic healthy  persons. Taking the results of previous reports into counts, decrease in HDL and HDL-Ch seems to contribute to the development of dyslipoproteinemia (broad-midband lipoproteinemia; an accumulation of the intermediate Lp or the remnant Lps) in hemodialysis patients. The results of the present study suggest that protective function proposed by the previous workers of HDL against atherosclerosis may be operated by facilitating the elimination of the accumulated midband Lps.", "contents": "Serum high density lipoprotein in hemodialysis patients. Uremic patients on prolonged maintenance hemodialysis (hemodialysis patients) are at high risk for atherosclerotic cardiovascular complications. To investigate the serum lipoprotein (Lp) abnormalities in hemodialysis patients, high density Lp (HDL) concentration was determined using ultracentrifugal analysis and quantitative immunoelectrophoresis in 23 hemodialysis patients, 8 non-uremic hyperlipidemic subjects, and 12 normal subjects. Immunoreactive HDL as well as HDL-cholesterol (HDL-Ch) in hemodialysis patients was lower significantly than the level in patients with non-uremic hyperlipidemia or normolipidemic healthy  persons. Taking the results of previous reports into counts, decrease in HDL and HDL-Ch seems to contribute to the development of dyslipoproteinemia (broad-midband lipoproteinemia; an accumulation of the intermediate Lp or the remnant Lps) in hemodialysis patients. The results of the present study suggest that protective function proposed by the previous workers of HDL against atherosclerosis may be operated by facilitating the elimination of the accumulated midband Lps."}
{"id": "PMID:213630", "title": "Screening of anti-B cell antibodies in the sera of renal transplant recipients by using Daudi cell line.", "content": "In order to examine the presence of antibodies against B cells, 83 sera obtained from 55 renal transplant recipients were screened by microcytotoxicity test using Daudi cell line. Out of 83 samples, 12 were pretransplant sera, 62 were post-transplant sera and 9 were from the patients whose grafts has been removed due to rejection. For the purpose of improving the reliability of the tests, 5 different rabbit complements were selected and cytotoxicity tests with them were carried out simultaneously. Pretransplant sera without blood transfusion did not show any cytotoxicity against Daudi cells. Although 42% of post-transplant sera showed cytotoxicity against Daudi cells, cytotoxic activity of the sera showed no relation with the occurrence of rejection episodes. Three serum samples out of 5 patients whose grafts had been removed due to rejection showed strong cytotoxicity against Daudi cells and the sera of 2 other patients did not. There was no relation between the cytotoxicity against Daudi cells and antibodies against Epstein-Barr virus capsid antigen in the post-transplant sera.", "contents": "Screening of anti-B cell antibodies in the sera of renal transplant recipients by using Daudi cell line. In order to examine the presence of antibodies against B cells, 83 sera obtained from 55 renal transplant recipients were screened by microcytotoxicity test using Daudi cell line. Out of 83 samples, 12 were pretransplant sera, 62 were post-transplant sera and 9 were from the patients whose grafts has been removed due to rejection. For the purpose of improving the reliability of the tests, 5 different rabbit complements were selected and cytotoxicity tests with them were carried out simultaneously. Pretransplant sera without blood transfusion did not show any cytotoxicity against Daudi cells. Although 42% of post-transplant sera showed cytotoxicity against Daudi cells, cytotoxic activity of the sera showed no relation with the occurrence of rejection episodes. Three serum samples out of 5 patients whose grafts had been removed due to rejection showed strong cytotoxicity against Daudi cells and the sera of 2 other patients did not. There was no relation between the cytotoxicity against Daudi cells and antibodies against Epstein-Barr virus capsid antigen in the post-transplant sera."}
{"id": "PMID:213633", "title": "Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. IV. Natural infection in sentinel pigs.", "content": "Natural infection with Japanese encephalitis virus in three sentinel pigs held in separate experimental huts was examined daily by virus recovery from blood samples of the pigs and from mosquitoes after incubation for about 7 days from their blood feeding and by HI antibody titration of the blood samples. After a period of low infection rates, below 6%, for about two weeks in engorged Culex tritaeniorhynchus summorosus, high mosquito infections of over 30% from each viremic pig occurred for two to three days. The pigs may be probably have been bitten by many infected but not infective mosquitoes in a period of about 10 days before infection.", "contents": "Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. IV. Natural infection in sentinel pigs. Natural infection with Japanese encephalitis virus in three sentinel pigs held in separate experimental huts was examined daily by virus recovery from blood samples of the pigs and from mosquitoes after incubation for about 7 days from their blood feeding and by HI antibody titration of the blood samples. After a period of low infection rates, below 6%, for about two weeks in engorged Culex tritaeniorhynchus summorosus, high mosquito infections of over 30% from each viremic pig occurred for two to three days. The pigs may be probably have been bitten by many infected but not infective mosquitoes in a period of about 10 days before infection."}
{"id": "PMID:213636", "title": "[Mechanism of action and clinical effectiveness of the new Soviet-made drug parmidin in the treatment of arteriosclerosis and ischemic heart disease].", "content": "The pharmacodynamics and efficacy of the new Soviet drug parmidin depending on the state of the coronary reserve are discussed on the basis of the results of observation over 176 patients suffering from chronic ischemic heart disease with affection of the peripheral arteries of the lower extremities. The activity of the drug in patients with atherosclerotic and diabetic affection of the arterial vessels is shown. The pharmacokinetics of parmidin in patients after the administration of a single 1.0 g dose was studied by determining its content in blood and urine 1, 2, 4, 8, 12, and 24 hours later. The effect of parmidin on the blood kinin system in patients with chronic ischemic heart disease was studied.", "contents": "[Mechanism of action and clinical effectiveness of the new Soviet-made drug parmidin in the treatment of arteriosclerosis and ischemic heart disease]. The pharmacodynamics and efficacy of the new Soviet drug parmidin depending on the state of the coronary reserve are discussed on the basis of the results of observation over 176 patients suffering from chronic ischemic heart disease with affection of the peripheral arteries of the lower extremities. The activity of the drug in patients with atherosclerotic and diabetic affection of the arterial vessels is shown. The pharmacokinetics of parmidin in patients after the administration of a single 1.0 g dose was studied by determining its content in blood and urine 1, 2, 4, 8, 12, and 24 hours later. The effect of parmidin on the blood kinin system in patients with chronic ischemic heart disease was studied."}
{"id": "PMID:213638", "title": "[Vaccine-related paralytic poliomyelitis with severe pareses. Report of one case (author's transl)].", "content": "In 11-year-old girl paralytic poliomyelitis developed 18 days after administration of trivalent oral poliomyelitis virus-vaccine. In spite of isolation and identification of vaccine-poliomyelitis-virus type III, there was only a slight raise of antibodies in the neutralisation-tests. The possibilities of lacking titer-raising is discussed, especially concerning the question of the claim to maintenance.", "contents": "[Vaccine-related paralytic poliomyelitis with severe pareses. Report of one case (author's transl)]. In 11-year-old girl paralytic poliomyelitis developed 18 days after administration of trivalent oral poliomyelitis virus-vaccine. In spite of isolation and identification of vaccine-poliomyelitis-virus type III, there was only a slight raise of antibodies in the neutralisation-tests. The possibilities of lacking titer-raising is discussed, especially concerning the question of the claim to maintenance."}
{"id": "PMID:213639", "title": "[A method for the evaluation of nitroblue tetrazolium reduction in human platelets (author's transl)].", "content": "A long term incubation in NBT-solution leads not only to NBT-reduction by polymorphnuclear leukocytes and monocytes, but also in washed human platelets. The reaction is enhanced by ADP and to a smaller and very variable extent also by Thrombin and Ristocetin. It is inhibited by incubation in plasma environment as well by DBcAMP and PGE1. After a detailed demonstration of the applied method, some possible biochemical mechanisms of the NBT-reduction in human platelets are discussed.", "contents": "[A method for the evaluation of nitroblue tetrazolium reduction in human platelets (author's transl)]. A long term incubation in NBT-solution leads not only to NBT-reduction by polymorphnuclear leukocytes and monocytes, but also in washed human platelets. The reaction is enhanced by ADP and to a smaller and very variable extent also by Thrombin and Ristocetin. It is inhibited by incubation in plasma environment as well by DBcAMP and PGE1. After a detailed demonstration of the applied method, some possible biochemical mechanisms of the NBT-reduction in human platelets are discussed."}
{"id": "PMID:213640", "title": "Activation of adipose tissue lipoprotein lipase by lipoprotein fractions from normals and patients with type v hyperlipoproteinemia.", "content": "The effects of the main lipoprotein density classes on the human adipose tissue lipoprotein lipase activity were studied. A dose-dependent stimulation of lipoprotein lipase activity was obtained for HDL and, to a lesser extent, for VLDL on a constant weight basis. LDL exerted virtually no effect. At higher concentrations, HDL as well as VLDL inhibited the stimulated lipolytic activity. In type V hyperlipoproteinemia, the stimulating effect of VLDL and of HDL was significantly lower, whereas the inhibiting action of HDL was markedly increased.", "contents": "Activation of adipose tissue lipoprotein lipase by lipoprotein fractions from normals and patients with type v hyperlipoproteinemia. The effects of the main lipoprotein density classes on the human adipose tissue lipoprotein lipase activity were studied. A dose-dependent stimulation of lipoprotein lipase activity was obtained for HDL and, to a lesser extent, for VLDL on a constant weight basis. LDL exerted virtually no effect. At higher concentrations, HDL as well as VLDL inhibited the stimulated lipolytic activity. In type V hyperlipoproteinemia, the stimulating effect of VLDL and of HDL was significantly lower, whereas the inhibiting action of HDL was markedly increased."}
{"id": "PMID:213641", "title": "Alcian blue staining intestinal goblet cell antigen (GOA): a marker for gastric signet ring cell and colonic colloidal carcinoma.", "content": "An Alcian blue staining, perchloric acid-soluble, antigenic acidic mucosubstance (GOA) was purified from human gastric signet ring cell carcinoma with DEAE-cellulose chromatography, Seqhadex G-200 and preparative polycrylamide gel electrophoresis. Specific antisera were raised which reacted in indirect immunoenzyme histology with normal goblet cells of the small and large intestine and with goblet cells of intestinalized gastric mucosa. In surgical resection specimens of the stomach (n = 100) and of the colon (n = 19) 3 gastric signet ring cell carcinomas and 3 colonic colloidal adenocarcinomas stained for GOA, demonstrating an immunochemical relationship with normal intestinal goblet cells.", "contents": "Alcian blue staining intestinal goblet cell antigen (GOA): a marker for gastric signet ring cell and colonic colloidal carcinoma. An Alcian blue staining, perchloric acid-soluble, antigenic acidic mucosubstance (GOA) was purified from human gastric signet ring cell carcinoma with DEAE-cellulose chromatography, Seqhadex G-200 and preparative polycrylamide gel electrophoresis. Specific antisera were raised which reacted in indirect immunoenzyme histology with normal goblet cells of the small and large intestine and with goblet cells of intestinalized gastric mucosa. In surgical resection specimens of the stomach (n = 100) and of the colon (n = 19) 3 gastric signet ring cell carcinomas and 3 colonic colloidal adenocarcinomas stained for GOA, demonstrating an immunochemical relationship with normal intestinal goblet cells."}
{"id": "PMID:213651", "title": "The effects of Clostridium perfringens enterotoxin on rat and rabbit ileum: an electron microscopic study.", "content": "Intestinal epithelial damage caused by Clostridium perfringens enterotoxin in rats and rabbits was identified by light microscopy and compared at the surface (scanning electron microscopy), and the ultrastructural (transmission electron microscopy) levels. Under the light microscope damage to the epithelial layer of villus tips was clearly evident in cross-sections. Whole tissue viewed under the scanning electron microscope showed comparable tip localization of morpholigic damage in the form of collapsed tips and a dense covering of rounded blebs on the tips. Ulstructuctural observations included partial and sometimes complete disappearance of microvilli structures, budding of the terminal web region into the lumen, and even complete destruction of epithelial cells. These data suggest that C. perfringens enterotoxin attacks the epithelial cells with a preference for cells at the villus tips and causes damage at least in part by altering the cells' apical membranes. This then leads to cellular sloughing, death, and lysing.", "contents": "The effects of Clostridium perfringens enterotoxin on rat and rabbit ileum: an electron microscopic study. Intestinal epithelial damage caused by Clostridium perfringens enterotoxin in rats and rabbits was identified by light microscopy and compared at the surface (scanning electron microscopy), and the ultrastructural (transmission electron microscopy) levels. Under the light microscope damage to the epithelial layer of villus tips was clearly evident in cross-sections. Whole tissue viewed under the scanning electron microscope showed comparable tip localization of morpholigic damage in the form of collapsed tips and a dense covering of rounded blebs on the tips. Ulstructuctural observations included partial and sometimes complete disappearance of microvilli structures, budding of the terminal web region into the lumen, and even complete destruction of epithelial cells. These data suggest that C. perfringens enterotoxin attacks the epithelial cells with a preference for cells at the villus tips and causes damage at least in part by altering the cells' apical membranes. This then leads to cellular sloughing, death, and lysing."}
{"id": "PMID:213652", "title": "Subpopulations of breast carcinoma defined by S-phase fraction, morphology, and estrogen receptor content.", "content": "The S-phase fraction (SPF), defined as the number of cells per hundred that showed evidence of nuclear DNA synthesis detectable by autoradiography after in vitro incubation with tritiated thymidine, was measured in 170 primary, invasive carcinomas of the breast. Assay for estrogen receptor was performed on tissue from 129 carcinomas, and 34 were also assayed for progesterone receptor. The concentration of estradiol-17 beta was measured in the serum of 69 patients. All carcinomas were analyzed for a variety of histologic features and were classified into morphologic types. SPF were lognormally distributed and were negatively correlated with the patient's age and presence of estrogen receptor, but not with presence of progesterone receptor, size of the carcinoma, number of axillary nodal metastases, or concentration of estradiol-17 beta in serum. The SPFs of lobular, mucinous, and tubular carcinomas were consistently low (geometric mean 1.2, range 0.05 to 3.55), and the SPFs of medullary and atypical medullary carcinomas were consistently high (geometric mean 14.0, range 7.77 to 20.2), whereas carcinomas of other types (not otherwise specified) had an intermediate geometric mean (4.7) and a broad range (0.09 to 25.4). The carcinomas that were not otherwise specified could be divided into three groups with different geometric mean SPFs by nuclear morphologic criteria (1.2 for minimal atypicality, 3.5 for moderate, and 7.9 for severe). Therefore it is possible to sort breast carcinomas histologically  into groups with low, intermediate, and high SPF. Correlations between SPF, estrogen receptor content, and microscopic morphology indicate the existence of distinctive subpopulations of breast carcinoma that may have epidemiologic and therapeutic importance.", "contents": "Subpopulations of breast carcinoma defined by S-phase fraction, morphology, and estrogen receptor content. The S-phase fraction (SPF), defined as the number of cells per hundred that showed evidence of nuclear DNA synthesis detectable by autoradiography after in vitro incubation with tritiated thymidine, was measured in 170 primary, invasive carcinomas of the breast. Assay for estrogen receptor was performed on tissue from 129 carcinomas, and 34 were also assayed for progesterone receptor. The concentration of estradiol-17 beta was measured in the serum of 69 patients. All carcinomas were analyzed for a variety of histologic features and were classified into morphologic types. SPF were lognormally distributed and were negatively correlated with the patient's age and presence of estrogen receptor, but not with presence of progesterone receptor, size of the carcinoma, number of axillary nodal metastases, or concentration of estradiol-17 beta in serum. The SPFs of lobular, mucinous, and tubular carcinomas were consistently low (geometric mean 1.2, range 0.05 to 3.55), and the SPFs of medullary and atypical medullary carcinomas were consistently high (geometric mean 14.0, range 7.77 to 20.2), whereas carcinomas of other types (not otherwise specified) had an intermediate geometric mean (4.7) and a broad range (0.09 to 25.4). The carcinomas that were not otherwise specified could be divided into three groups with different geometric mean SPFs by nuclear morphologic criteria (1.2 for minimal atypicality, 3.5 for moderate, and 7.9 for severe). Therefore it is possible to sort breast carcinomas histologically  into groups with low, intermediate, and high SPF. Correlations between SPF, estrogen receptor content, and microscopic morphology indicate the existence of distinctive subpopulations of breast carcinoma that may have epidemiologic and therapeutic importance."}
{"id": "PMID:213661", "title": "Local regulation of lipolysis in adipose tissue by fatty acids, prostaglandins and adenosine.", "content": "From this review of the literature the following tentative conclusions may be drawn: 1) The relationship between cyclic AMP and lipolysis is not linear. In particular, only very small elevations of cyclic AMP appear to be necessary for essentially maximal lipolysis. One consequence of this is that some of the studies concerning feed-back regulation of cyclic AMP may not be relevant to our understanding of the regulation of lipolysis. 2) The only substances for which a firm role as feed-back regulators has been documented are free fatty acids. Their importance under in vivo conditions are, however, not settled. 3) The bulk of the present evidence fails to suggest a role for endogenous prostaglandins (and related compounds) as feed-back regulators of lipolysis. 4) There is considerable evidence that endogenous adenosine modulates lipolysis in vivo and in vitro. Adenosine does not appear to act as a feed-back regulator in the strict sense but the formation of adenosine may be enhanced under conditions of lipolysis because of simultaneously occurring breakdown of ATP.", "contents": "Local regulation of lipolysis in adipose tissue by fatty acids, prostaglandins and adenosine. From this review of the literature the following tentative conclusions may be drawn: 1) The relationship between cyclic AMP and lipolysis is not linear. In particular, only very small elevations of cyclic AMP appear to be necessary for essentially maximal lipolysis. One consequence of this is that some of the studies concerning feed-back regulation of cyclic AMP may not be relevant to our understanding of the regulation of lipolysis. 2) The only substances for which a firm role as feed-back regulators has been documented are free fatty acids. Their importance under in vivo conditions are, however, not settled. 3) The bulk of the present evidence fails to suggest a role for endogenous prostaglandins (and related compounds) as feed-back regulators of lipolysis. 4) There is considerable evidence that endogenous adenosine modulates lipolysis in vivo and in vitro. Adenosine does not appear to act as a feed-back regulator in the strict sense but the formation of adenosine may be enhanced under conditions of lipolysis because of simultaneously occurring breakdown of ATP."}
{"id": "PMID:213664", "title": "Angiography in the diagnosis and management of extracranial vascular lesions of the head and neck.", "content": "The angiographic features of various lesions of the head and neck are presented. Angiographically, cavernous hemangiomas display large venous lakes with calcified phleboliths. Arteriovenous malformations reveal massive tumor stain with well delineated feeding vessels from multiple systems. Chemodectomas and juvenile nasopharyngeal angiofibromas are clearly vascular with homogenous tumor staining in the capillary phase. Angiography of cavernous hemangioma, AVM, chemodectoma, and angiofibroma is diagnostic and may preclude the need for tissue biopsy. Angiographically neurilemmomas are less vascular with non-homogenous tumor stain. Carcinomas are typically avascular. The use and benefits of arterial embolization in the management of these lesions is presented.", "contents": "Angiography in the diagnosis and management of extracranial vascular lesions of the head and neck. The angiographic features of various lesions of the head and neck are presented. Angiographically, cavernous hemangiomas display large venous lakes with calcified phleboliths. Arteriovenous malformations reveal massive tumor stain with well delineated feeding vessels from multiple systems. Chemodectomas and juvenile nasopharyngeal angiofibromas are clearly vascular with homogenous tumor staining in the capillary phase. Angiography of cavernous hemangioma, AVM, chemodectoma, and angiofibroma is diagnostic and may preclude the need for tissue biopsy. Angiographically neurilemmomas are less vascular with non-homogenous tumor stain. Carcinomas are typically avascular. The use and benefits of arterial embolization in the management of these lesions is presented."}
{"id": "PMID:213697", "title": "Cell-mediated immunity to mouse adenovirus infection. Macrophage migration inhibition test.", "content": "Cell-mediated immunity (CMI) to mouse adenovirus (M-Ad) infection was studied by macrophage migration inhibition test (MMI) as one of in vitro correlates of CMI. Both direct and indirect tests showed clearly that migration of packed peritoneal exudate cells (PEC) (immune mouse or nonimmune guinea pig) was remarkably inhibited; MIF was produced by interactions between immune PEC and infected cell extracts and between immune spleen cells and infected cells or their extracts. The antigen(s) responsible for the above MMI was demonstrated in 6- to 12-hour infected ME cells, and FUdR-treated infected ME cells. Since under these conditions there is S antigen(s) synthesis but not capsid antigen synthesis, the antigen(s) concerned must be an S antigen(s). T cells sensitized to infected cells were shown to be required to induce MMI. The MMI is specific for M-Ad, since no cross MMI was observed between M-Ad and SV40 systems. Time course study of the development of CMI to M-Ad by MMI tests showed that CMI became detectable 4 days post-infection (pi), reached its peak level about 10 days pi, and faded away rapidly in about 10 days thereafter.", "contents": "Cell-mediated immunity to mouse adenovirus infection. Macrophage migration inhibition test. Cell-mediated immunity (CMI) to mouse adenovirus (M-Ad) infection was studied by macrophage migration inhibition test (MMI) as one of in vitro correlates of CMI. Both direct and indirect tests showed clearly that migration of packed peritoneal exudate cells (PEC) (immune mouse or nonimmune guinea pig) was remarkably inhibited; MIF was produced by interactions between immune PEC and infected cell extracts and between immune spleen cells and infected cells or their extracts. The antigen(s) responsible for the above MMI was demonstrated in 6- to 12-hour infected ME cells, and FUdR-treated infected ME cells. Since under these conditions there is S antigen(s) synthesis but not capsid antigen synthesis, the antigen(s) concerned must be an S antigen(s). T cells sensitized to infected cells were shown to be required to induce MMI. The MMI is specific for M-Ad, since no cross MMI was observed between M-Ad and SV40 systems. Time course study of the development of CMI to M-Ad by MMI tests showed that CMI became detectable 4 days post-infection (pi), reached its peak level about 10 days pi, and faded away rapidly in about 10 days thereafter."}
{"id": "PMID:213699", "title": "A new microplate neutralization test for typing of herpes simplex virus.", "content": "A microplate serum neutralization test for estimation of complement-requiring neutralizing (CRN) antibody was established as the first step for simplification of typing of herpes simplex virus (HSV). When guinea pigs were immunized with type 2 HSV, the late sera could mostly differentiate the types of HSV better than hyperimmune rabbit sera, the CRN titer against the heterologous type 1 HSV being much lower than the homologous titer. Sera of guinea pigs immunized with type 1 HSV showed about the same level of cross reaction against type 2 HSV as did rabbit antisera. Guinea pig sera having minimal levels of cross reaction were selected, and their high dilution (1:160) and complement were added to serial 10-fold dilutions of virus in the microplate titration of virus infectivity. Selective reduction of virus titer by either antiserum could determine the type of HSV. No equivocal intermediate case was found among a number of stock strains including many fresh isolates. The typing result coincided with that determined by a modification of Yang et al's method based on virus titers obtained with Vero and primary chick embryo cells. The typing based on plaquing in chick embryo cells sometimes failed to identify type 1 HSV.", "contents": "A new microplate neutralization test for typing of herpes simplex virus. A microplate serum neutralization test for estimation of complement-requiring neutralizing (CRN) antibody was established as the first step for simplification of typing of herpes simplex virus (HSV). When guinea pigs were immunized with type 2 HSV, the late sera could mostly differentiate the types of HSV better than hyperimmune rabbit sera, the CRN titer against the heterologous type 1 HSV being much lower than the homologous titer. Sera of guinea pigs immunized with type 1 HSV showed about the same level of cross reaction against type 2 HSV as did rabbit antisera. Guinea pig sera having minimal levels of cross reaction were selected, and their high dilution (1:160) and complement were added to serial 10-fold dilutions of virus in the microplate titration of virus infectivity. Selective reduction of virus titer by either antiserum could determine the type of HSV. No equivocal intermediate case was found among a number of stock strains including many fresh isolates. The typing result coincided with that determined by a modification of Yang et al's method based on virus titers obtained with Vero and primary chick embryo cells. The typing based on plaquing in chick embryo cells sometimes failed to identify type 1 HSV."}
{"id": "PMID:213702", "title": "The cyclic 3',5'-adenosine monophosphate receptor protein and regulation of cyclic 3',5'-adenosine monophosphate synthesis in Escherichia coli.", "content": "Rates of synthesis of cyclic 3',5'-adenosine monophosphate (cAMP) were measured in cultures of Escherichia coli aerating without a carbon source. This technique provides a representative measure of adenylate cyclase activity in the absence of inhibition caused by transport of the carbon source. Adenylate cyclase activity was found to vary more than 20-fold depending on the carbon source that had been available during growth. Synthesis of cAMP in cells aerating in the absence of the carbon source was highest when cells had been grown with glucose or fructose which inhibit adenylate cyclase activity severely. Synthesis of cAMP was much lower when cells had been grown with glycerol or succinate which cause only minimal inhibition of the activity. The variation in cAMP synthesis due to different carbon sources requires a functional cAMP receptor protein (CRP). Crp- mutants synthesize cAMP at comparable rates regardless of the carbon source that afforded growth. A novel mutant of E. coli having a CRP no longer dependent on cAMP has been isolated and characterized. Adenylate cyclase activity in this mutant no longer responds normally to variations in the carbon source.", "contents": "The cyclic 3',5'-adenosine monophosphate receptor protein and regulation of cyclic 3',5'-adenosine monophosphate synthesis in Escherichia coli. Rates of synthesis of cyclic 3',5'-adenosine monophosphate (cAMP) were measured in cultures of Escherichia coli aerating without a carbon source. This technique provides a representative measure of adenylate cyclase activity in the absence of inhibition caused by transport of the carbon source. Adenylate cyclase activity was found to vary more than 20-fold depending on the carbon source that had been available during growth. Synthesis of cAMP in cells aerating in the absence of the carbon source was highest when cells had been grown with glucose or fructose which inhibit adenylate cyclase activity severely. Synthesis of cAMP was much lower when cells had been grown with glycerol or succinate which cause only minimal inhibition of the activity. The variation in cAMP synthesis due to different carbon sources requires a functional cAMP receptor protein (CRP). Crp- mutants synthesize cAMP at comparable rates regardless of the carbon source that afforded growth. A novel mutant of E. coli having a CRP no longer dependent on cAMP has been isolated and characterized. Adenylate cyclase activity in this mutant no longer responds normally to variations in the carbon source."}
{"id": "PMID:213700", "title": "[Paramagnetic properties of the conidial pigments of Aspergillus niger and Penicillium notatum fungi isolated from the mesosphere].", "content": "The conidia of Aspergillus niger and Penicillium notatum detected in the upper atmospheric layers of the Earth (58--77 km) were found to contain stable paramagnetic centres (PMC) at concentrations of 0.2 X 10(18) and 1.6 X 10(18) per gram of dry biomass, respectively. Aspergillin, the black pigment of Asp. niger, was shown to have (0.1--0.6) X 10(18) PMC per gram of dry substance (depending on the fraction). Stable paramagnetism of the conidial pigments with respect to their active protecting action in vivo is discussed on the basis of these data.", "contents": "[Paramagnetic properties of the conidial pigments of Aspergillus niger and Penicillium notatum fungi isolated from the mesosphere]. The conidia of Aspergillus niger and Penicillium notatum detected in the upper atmospheric layers of the Earth (58--77 km) were found to contain stable paramagnetic centres (PMC) at concentrations of 0.2 X 10(18) and 1.6 X 10(18) per gram of dry biomass, respectively. Aspergillin, the black pigment of Asp. niger, was shown to have (0.1--0.6) X 10(18) PMC per gram of dry substance (depending on the fraction). Stable paramagnetism of the conidial pigments with respect to their active protecting action in vivo is discussed on the basis of these data."}
{"id": "PMID:213705", "title": "[Granular cell myoblastoma].", "content": "Authors report a case of multiplex myoblastoma of the skin observed at a male patient aged 34. Epidermies covering the tumour histologically did not show hyperplasia considered to be characteristic. 8 years after the removal of the tumour the patient is well.", "contents": "[Granular cell myoblastoma]. Authors report a case of multiplex myoblastoma of the skin observed at a male patient aged 34. Epidermies covering the tumour histologically did not show hyperplasia considered to be characteristic. 8 years after the removal of the tumour the patient is well."}
{"id": "PMID:213706", "title": "[2 cases of sympathetic paraganglioma of the urinary bladder].", "content": "Two cases of symphathetic paraganglioma of the urinary bladder are reported. Symppathetic- or parasymphatetic origin of intramural paraganlia or paragangliomas can be determined by demonstration of praesynaptic myelinated fibers. This method gives more reliable results than formaldehyd-induction-method carried out on freezed sections or the G\u00f6m\u00f6ri's chromaffin reaction which often appears to be false-negative.", "contents": "[2 cases of sympathetic paraganglioma of the urinary bladder]. Two cases of symphathetic paraganglioma of the urinary bladder are reported. Symppathetic- or parasymphatetic origin of intramural paraganlia or paragangliomas can be determined by demonstration of praesynaptic myelinated fibers. This method gives more reliable results than formaldehyd-induction-method carried out on freezed sections or the G\u00f6m\u00f6ri's chromaffin reaction which often appears to be false-negative."}
{"id": "PMID:213710", "title": "Comparison of toxicity and mutagenicity of butyl methanesulfonate among human lymphoblast lines.", "content": "The toxic and mutagenic effects of butyl methanesulfonate (BMS) were compared among four diploid human lymphoblast lines, MIT-2, WI-L2, MGL8B-2 and GM 130. The toxic and mutagenic effects of 24-h exposure to BMS were similar for the MIT-2, WI-L2 and MGL8B-2 lines, while the GM 130 line was strikingly resistant to the toxic and mutagenic effects of BMS.", "contents": "Comparison of toxicity and mutagenicity of butyl methanesulfonate among human lymphoblast lines. The toxic and mutagenic effects of butyl methanesulfonate (BMS) were compared among four diploid human lymphoblast lines, MIT-2, WI-L2, MGL8B-2 and GM 130. The toxic and mutagenic effects of 24-h exposure to BMS were similar for the MIT-2, WI-L2 and MGL8B-2 lines, while the GM 130 line was strikingly resistant to the toxic and mutagenic effects of BMS."}
{"id": "PMID:213712", "title": "Rapid diagnosis of cytomegalovirus infection in infants by electron microscopy.", "content": "Electron microscopy was applied to the diagnosis of cytomegalovirus infection in infants; we used the pseudoreplica method, which permits detection of herpesvirus particles within 15 to 30 minutes. Viruses were most readily detectable in urines with infectivity titers greater than or equal to 10(4) per milliliter (95 per cent correlation with the tissue-culture method). Virus particles were detected in 18 of 20 urines obtained from symptomatic or asymptomatic, congenitally or postnatally acquired cytomegalovirus infections in infants younger than six months. Viruses were demonstrated in six of 14 infants older than six months, whose urines usually contained greater than 10(4) per milliliter. All five oral specimens examined by electron microscopy were also positive. Viruses were readily detectable in specimens stored or shipped at 4 degrees C for several days, thus permitting physicians anywhere to obtain confirmation of a herpesvirus infection (presumably cytomegalovirus) within one to two days.", "contents": "Rapid diagnosis of cytomegalovirus infection in infants by electron microscopy. Electron microscopy was applied to the diagnosis of cytomegalovirus infection in infants; we used the pseudoreplica method, which permits detection of herpesvirus particles within 15 to 30 minutes. Viruses were most readily detectable in urines with infectivity titers greater than or equal to 10(4) per milliliter (95 per cent correlation with the tissue-culture method). Virus particles were detected in 18 of 20 urines obtained from symptomatic or asymptomatic, congenitally or postnatally acquired cytomegalovirus infections in infants younger than six months. Viruses were demonstrated in six of 14 infants older than six months, whose urines usually contained greater than 10(4) per milliliter. All five oral specimens examined by electron microscopy were also positive. Viruses were readily detectable in specimens stored or shipped at 4 degrees C for several days, thus permitting physicians anywhere to obtain confirmation of a herpesvirus infection (presumably cytomegalovirus) within one to two days."}
{"id": "PMID:213715", "title": "Defective high-density lipoprotein composition in patients on chronic hemodialysis. A possible mechanism for accelerated atherosclerosis.", "content": "We determined serum high-density lipoprotein cholesterol content and analyzed the approtein structure of the various lipoprotein fractions in 21 patients on chronic hemodialysis. High-density lipoprotein cholesterol was significantly reduced in all patients as compared with 11 normal persons (mean +/-1 standard deviation: 26 +/- 13 vs. 52 +/- 9 mg per 100 ml; P less than 0.001) whether or not triglyceride levels were raised. In seven of those with Type IV hyperlipoproteinemia, protein content of high-density lipoprotein and its subfractions 1, 2 and 3 were also reduced (P less than 0.001) in parallel with reductions in cholesterol in these fractions. Apoprotein electrophoresis showed an increase in \"arginine-rich\" peptide in very-low-density lipoprotein and high-density lipoprotein fraction 1, and a reduction in apoprotein Cll in very-low-density and high-density lipoprotein. In addition to their reduced high-density lipoprotein cholesterol levels, a major factor in the atherosclerosis of these patients may be their abnormal high-density lipoprotein composition. Their raised triglyceride levels could be due to defective lipoprotein lipase activation by the reduced very-low-density lipoprotein apoprotein.", "contents": "Defective high-density lipoprotein composition in patients on chronic hemodialysis. A possible mechanism for accelerated atherosclerosis. We determined serum high-density lipoprotein cholesterol content and analyzed the approtein structure of the various lipoprotein fractions in 21 patients on chronic hemodialysis. High-density lipoprotein cholesterol was significantly reduced in all patients as compared with 11 normal persons (mean +/-1 standard deviation: 26 +/- 13 vs. 52 +/- 9 mg per 100 ml; P less than 0.001) whether or not triglyceride levels were raised. In seven of those with Type IV hyperlipoproteinemia, protein content of high-density lipoprotein and its subfractions 1, 2 and 3 were also reduced (P less than 0.001) in parallel with reductions in cholesterol in these fractions. Apoprotein electrophoresis showed an increase in \"arginine-rich\" peptide in very-low-density lipoprotein and high-density lipoprotein fraction 1, and a reduction in apoprotein Cll in very-low-density and high-density lipoprotein. In addition to their reduced high-density lipoprotein cholesterol levels, a major factor in the atherosclerosis of these patients may be their abnormal high-density lipoprotein composition. Their raised triglyceride levels could be due to defective lipoprotein lipase activation by the reduced very-low-density lipoprotein apoprotein."}
{"id": "PMID:213719", "title": "Inheritance of apolipoprotein C-II deficiency with hypertriglyceridemia and pancreatitis.", "content": "A study of the relatives of a patient with apolipoprotein C-II deficiency showed that the defect is inherited as an autosomal recessive trait. The kindred studied originated from an isolated population in which considerable inbreeding has occurred for 140 years. Seven homozygotes had marked fasting chylomicronemia and triglyceridemia, and lacked detectable apolipoprotein C-II by several assay methods. Five homozygotes had experienced one to many attacks of pancreatitis from as early as six years of age. Obligate heterozygotes had apolipoprotein C-II concentrations about 30 to 50 per cent of normal values and had normal plasma triglyceride concentrations. This metabolic defect should be considered in patients with markedly elevated plasma triglycerides who have apparent lipoprotein lipase deficiency, and usually also have pancreatitis.", "contents": "Inheritance of apolipoprotein C-II deficiency with hypertriglyceridemia and pancreatitis. A study of the relatives of a patient with apolipoprotein C-II deficiency showed that the defect is inherited as an autosomal recessive trait. The kindred studied originated from an isolated population in which considerable inbreeding has occurred for 140 years. Seven homozygotes had marked fasting chylomicronemia and triglyceridemia, and lacked detectable apolipoprotein C-II by several assay methods. Five homozygotes had experienced one to many attacks of pancreatitis from as early as six years of age. Obligate heterozygotes had apolipoprotein C-II concentrations about 30 to 50 per cent of normal values and had normal plasma triglyceride concentrations. This metabolic defect should be considered in patients with markedly elevated plasma triglycerides who have apparent lipoprotein lipase deficiency, and usually also have pancreatitis."}
{"id": "PMID:213720", "title": "Apoprotein A-I synthesis in normal intestinal mucosa and in Tangier disease.", "content": "To determine whether human small intestine synthesizes apoA-I, the major apoprotein of plasma high-density lipoproteins, we used immunofluorescence technics and monospecific antiserums to visualize apoA-I within intestinal epithelial cells from four normal subjects and one patient with Tangier disease. Biopsies from all subjects during fasting showed limited fluorescence. After lipid feeding intracellular apoA-I markedly increased in both normal subjects and the patient. During alimentary lipemia, mean plasma apoA-I levels (milligrams per deciliter) increased in four normal subjects from 161 +/- 12 (+/- S.E.M.) to 180 +/- 15 (P less than 0.05) and in the patient from 1.9 to 6.8. Normal plasma chylomicrons contained apoB, apoE and the C peptides but not apoA-I. The patient's chylomicrons contained ap0A-I. Normal and Tangier-disease intestinal-mucosa cells increase their content of apoA-I during chylomicron formation and subsequently contribute to plasma apoA-I levels. The low levels of apoA-I in Tangier disease are not due to a failure of intestinal synthesis but might be due to abnormal metabolism of chylomicron apoproteins.", "contents": "Apoprotein A-I synthesis in normal intestinal mucosa and in Tangier disease. To determine whether human small intestine synthesizes apoA-I, the major apoprotein of plasma high-density lipoproteins, we used immunofluorescence technics and monospecific antiserums to visualize apoA-I within intestinal epithelial cells from four normal subjects and one patient with Tangier disease. Biopsies from all subjects during fasting showed limited fluorescence. After lipid feeding intracellular apoA-I markedly increased in both normal subjects and the patient. During alimentary lipemia, mean plasma apoA-I levels (milligrams per deciliter) increased in four normal subjects from 161 +/- 12 (+/- S.E.M.) to 180 +/- 15 (P less than 0.05) and in the patient from 1.9 to 6.8. Normal plasma chylomicrons contained apoB, apoE and the C peptides but not apoA-I. The patient's chylomicrons contained ap0A-I. Normal and Tangier-disease intestinal-mucosa cells increase their content of apoA-I during chylomicron formation and subsequently contribute to plasma apoA-I levels. The low levels of apoA-I in Tangier disease are not due to a failure of intestinal synthesis but might be due to abnormal metabolism of chylomicron apoproteins."}
{"id": "PMID:213722", "title": "Endometrial cancer and estrogen use. Report of a large case-control study.", "content": "Our case-control study of the relation between estrogen use and endometrial cancer involved 451 cases and 888 controls. The overall risk of endometrial carcinoma was sixfold for estrogen users as compared with nonusers; long-term users (greater than five years) had a 15-fold risk. Excess risk was present for both diethylstilberstrol and conjugated estrogens. The risk associated with cyclic use was as great as that for continuous use. Increased risk was associated with estrogen use for all histologic grades of the tumor. The risk of advanced-stage carcinoma was fourfold for estrogen users, but rhe confidence interval was wide, and this question requires further study. Finally, this investigation contradicts the speculation that the association between this cancer and estrogen use can be explained by swifter diagnosis for estrogen users, misclassification of estrogen-related hyperplasia or treatment of early symptoms of the tumor with estrogen.", "contents": "Endometrial cancer and estrogen use. Report of a large case-control study. Our case-control study of the relation between estrogen use and endometrial cancer involved 451 cases and 888 controls. The overall risk of endometrial carcinoma was sixfold for estrogen users as compared with nonusers; long-term users (greater than five years) had a 15-fold risk. Excess risk was present for both diethylstilberstrol and conjugated estrogens. The risk associated with cyclic use was as great as that for continuous use. Increased risk was associated with estrogen use for all histologic grades of the tumor. The risk of advanced-stage carcinoma was fourfold for estrogen users, but rhe confidence interval was wide, and this question requires further study. Finally, this investigation contradicts the speculation that the association between this cancer and estrogen use can be explained by swifter diagnosis for estrogen users, misclassification of estrogen-related hyperplasia or treatment of early symptoms of the tumor with estrogen."}
{"id": "PMID:213723", "title": "Role of the conidium in dimorphism of Blastomyces dermatitidis.", "content": "Fine details of yeastlike cell development of Blastomyces dermatitidis from its conidium are described and illustrated by electron micrographs. When cultured in an enriched medium at 37C, conidia of two strains of B. dermatitidis readily underwent ultrastructural changes consistent with mycelial to yeast dimorphism. Although hyphal cells contained in the conversion cultures were observed consistently to undergo profound degenerative changes, the conidia rapidly germinated to give rise to short germ tubes which subsequently enlarged to form intermediate yeast mother cells (YMC). The wall of the germ tube arose from the innermost layer of the wall of the germinant. During the transition globoid osmiophilic inclusions of unknown origin and function were observed in vacuolated areas of the germ tube and YMC cytoplasm. Yeastlike daughter cells then budded from the intermediate YMC. Since transformation was readily accomplished under in vitro conditions favoring mycelial to yeast dimorphism, it is suggested that the conidium of B. dermatitidis represents the primary infective unit of this pathogenic fungus.", "contents": "Role of the conidium in dimorphism of Blastomyces dermatitidis. Fine details of yeastlike cell development of Blastomyces dermatitidis from its conidium are described and illustrated by electron micrographs. When cultured in an enriched medium at 37C, conidia of two strains of B. dermatitidis readily underwent ultrastructural changes consistent with mycelial to yeast dimorphism. Although hyphal cells contained in the conversion cultures were observed consistently to undergo profound degenerative changes, the conidia rapidly germinated to give rise to short germ tubes which subsequently enlarged to form intermediate yeast mother cells (YMC). The wall of the germ tube arose from the innermost layer of the wall of the germinant. During the transition globoid osmiophilic inclusions of unknown origin and function were observed in vacuolated areas of the germ tube and YMC cytoplasm. Yeastlike daughter cells then budded from the intermediate YMC. Since transformation was readily accomplished under in vitro conditions favoring mycelial to yeast dimorphism, it is suggested that the conidium of B. dermatitidis represents the primary infective unit of this pathogenic fungus."}
{"id": "PMID:213725", "title": "Structure-activity studies of narcotic agonists and antagonists from quantum chemical calculations.", "content": "Three classes of flexible opiates have been studied: 4-phenyl piperdines, methadone and enkephalins. Our results show that low energy conformers of the 4-phenyl piperidines have equatorial phenyl rings and cannot completely overlap with rigid opiates at the receptor. A combination of calculated conformational and electronic properties could account for observed potency differences in meperidine, desmethyl, alpha+, alpha-, beta+ and beta- prodines. Our results also indicate that both meperidine and its reverse ester bind to the receptor in a similar mode with the phi ring in approximmately the same position as the phenyl substituent in 5-phenyl benzomorphans. Conformers of methadone which maximally resemble morphine have very high relative energies. The lowest energy conformer has a partial H-bond between the NH and O=C groups. In this conformation methadone resembles meperidine more than morphine. The electronic structure of all three types of opiates indicate a similar cationic charge distribution around the amine nitrogen and imply that their binding to an anionic receptor site could be similar. The determination of peptide opiate conformations present a challenge of a different order of magnitude than the most flexibe exogenous opiates. Because of the extremely large number of possible conformations, search strategies based on energy optimized conformations alone are not adequate to select plausible receptor site candidates. Other criteria such as consistency with known structure activity data and similarities to rigid opiates must be used. With this rationale, we have predicted and characterized a low energy conformer of Met-enkephalin and D-ala2 Met-enkephalin as a likely candidate at the receptor site. With a modest energy input (deltaE approximately 3 kcal/mole) significant overlap of this conformer with the potent opiate PET was obtained. The tyrosine and phenyalanine side chains and the terminal amine and carboxyl groups play a crucial role in this overlap. It is hoped that this calculation with help establish a template for peptide opiate receptor interactions.", "contents": "Structure-activity studies of narcotic agonists and antagonists from quantum chemical calculations. Three classes of flexible opiates have been studied: 4-phenyl piperdines, methadone and enkephalins. Our results show that low energy conformers of the 4-phenyl piperidines have equatorial phenyl rings and cannot completely overlap with rigid opiates at the receptor. A combination of calculated conformational and electronic properties could account for observed potency differences in meperidine, desmethyl, alpha+, alpha-, beta+ and beta- prodines. Our results also indicate that both meperidine and its reverse ester bind to the receptor in a similar mode with the phi ring in approximmately the same position as the phenyl substituent in 5-phenyl benzomorphans. Conformers of methadone which maximally resemble morphine have very high relative energies. The lowest energy conformer has a partial H-bond between the NH and O=C groups. In this conformation methadone resembles meperidine more than morphine. The electronic structure of all three types of opiates indicate a similar cationic charge distribution around the amine nitrogen and imply that their binding to an anionic receptor site could be similar. The determination of peptide opiate conformations present a challenge of a different order of magnitude than the most flexibe exogenous opiates. Because of the extremely large number of possible conformations, search strategies based on energy optimized conformations alone are not adequate to select plausible receptor site candidates. Other criteria such as consistency with known structure activity data and similarities to rigid opiates must be used. With this rationale, we have predicted and characterized a low energy conformer of Met-enkephalin and D-ala2 Met-enkephalin as a likely candidate at the receptor site. With a modest energy input (deltaE approximately 3 kcal/mole) significant overlap of this conformer with the potent opiate PET was obtained. The tyrosine and phenyalanine side chains and the terminal amine and carboxyl groups play a crucial role in this overlap. It is hoped that this calculation with help establish a template for peptide opiate receptor interactions."}
{"id": "PMID:213737", "title": "The effect of cGMP in rabbit auricle as studied by a cut-end method.", "content": "Cyclic GMP was applied to the rabbit right auricle by a cut-end method. The nucleotide decreased the spontaneous rate, hyperpolarized the cell membrane and reduced the amplitude and the slow component of the action potential. It also decreased the force of contraction. These results suggest that cGMP may be the mediator of the action of acetylcholine in the rabbit auricle.", "contents": "The effect of cGMP in rabbit auricle as studied by a cut-end method. Cyclic GMP was applied to the rabbit right auricle by a cut-end method. The nucleotide decreased the spontaneous rate, hyperpolarized the cell membrane and reduced the amplitude and the slow component of the action potential. It also decreased the force of contraction. These results suggest that cGMP may be the mediator of the action of acetylcholine in the rabbit auricle."}
{"id": "PMID:213738", "title": "[Neurological examinations of workers with chronic exposure to manganese dioxide during the production of piles and batteries].", "content": "The authors examined 118 workers making piles and batteries under conditions of exposure to toxic action of manganese dioxide dust. Neurological and EEG investigations showed presence of pyramidal tract lesion signs in 16.9% of workers, extrapyramidal syndromes in 6.8%, peripheral nervous system involvement in 13.5% and neurotic complaints in 42.4%. The frequency of neurological manifestations was directly proportional to the duration of work in exposure. The difference in the frequency of neurotic complaints and signs of peripheral and central nervous system damage was statistically significant between the group exposed to manganese dioxide and the control group. EEG investigations were performed in 51 workers and abnormalities were found in 21 cases.", "contents": "[Neurological examinations of workers with chronic exposure to manganese dioxide during the production of piles and batteries]. The authors examined 118 workers making piles and batteries under conditions of exposure to toxic action of manganese dioxide dust. Neurological and EEG investigations showed presence of pyramidal tract lesion signs in 16.9% of workers, extrapyramidal syndromes in 6.8%, peripheral nervous system involvement in 13.5% and neurotic complaints in 42.4%. The frequency of neurological manifestations was directly proportional to the duration of work in exposure. The difference in the frequency of neurotic complaints and signs of peripheral and central nervous system damage was statistically significant between the group exposed to manganese dioxide and the control group. EEG investigations were performed in 51 workers and abnormalities were found in 21 cases."}
{"id": "PMID:213739", "title": "[Cerebrospinal fluid pressure measurements in the ventricular system during and after surgery in patients with supratentorial brain tumors].", "content": "In the light of CSFP measurements by Lundberg's method in 46 patients the authors showed the role of hyperventilation in lowering of intracranial pressure. A considerable efficacy of dexamethasone was demonstrated as well, the use of this drug permitted to achieve stabilization of CSFP during and after the operation. The investigations showed a considerable effectiveness of such drugs as mannitol and furosemide in lowering of CSFP. Pancuronium was found to be superior to suxamethonium for administration during induction of anaesthesia because the former caused no CSFP rise. In polygraphic investigations of nocturnal sleep with parallel recording of CSFP a rise of CSFP was demonstrated during REM phase of sleep.", "contents": "[Cerebrospinal fluid pressure measurements in the ventricular system during and after surgery in patients with supratentorial brain tumors]. In the light of CSFP measurements by Lundberg's method in 46 patients the authors showed the role of hyperventilation in lowering of intracranial pressure. A considerable efficacy of dexamethasone was demonstrated as well, the use of this drug permitted to achieve stabilization of CSFP during and after the operation. The investigations showed a considerable effectiveness of such drugs as mannitol and furosemide in lowering of CSFP. Pancuronium was found to be superior to suxamethonium for administration during induction of anaesthesia because the former caused no CSFP rise. In polygraphic investigations of nocturnal sleep with parallel recording of CSFP a rise of CSFP was demonstrated during REM phase of sleep."}
{"id": "PMID:213743", "title": "Enkephalins and nigrostriatal function.", "content": "Unilateral lesions of the substantia nigra were made with 6-hydroxydopamine in rats. In this model, drugs such as naloxone, which block endogenous enkephalin receptors, potentiated agents with postsynaptic dopaminergic actions, while antagonizing agents with presynaptic dopaminergic actions. Drugs which increase brain enkephalin content (d-phenylalanine or methionine-enkephalin) antagonized postsynaptically active agents and potentiated presynaptic agents. Naloxone also reversed reserpine-induced parkinsonism in rats. Separate pre- and postsynaptic enkephalinergic neurons thus seem to modulate nigrostriatal function.", "contents": "Enkephalins and nigrostriatal function. Unilateral lesions of the substantia nigra were made with 6-hydroxydopamine in rats. In this model, drugs such as naloxone, which block endogenous enkephalin receptors, potentiated agents with postsynaptic dopaminergic actions, while antagonizing agents with presynaptic dopaminergic actions. Drugs which increase brain enkephalin content (d-phenylalanine or methionine-enkephalin) antagonized postsynaptically active agents and potentiated presynaptic agents. Naloxone also reversed reserpine-induced parkinsonism in rats. Separate pre- and postsynaptic enkephalinergic neurons thus seem to modulate nigrostriatal function."}
{"id": "PMID:213740", "title": "Centrifugal and centripetal connections of the cat visual cortex.", "content": "In experiments on curarized cats unit responses in the dorsal lateral geniculate body to stimulation of various zones in area 17 of the visual cortex were analyzed. Of all cells tested 69% were found to respond antidromically and 8% orthodromically; in 7.6% of cells IPSPs occurred either after an initial antidromic spike or without it. The velocities of conduction of excitation along the corticopetal fibers of the optic radiation varied from 28 to 4.3 m/sec, but the three commonest groups of fibers had conduction velocities of 28-19, 14-12, and 10-9.5 m/sec. A difference between latent periods of antidromic responses of the same neurons was found to stimulation of different zones of the visual cortex; this indicates that axons of geniculo-cortical fibers split into several branches which form contacts with several neurons in area 17 of the visual cortex. The degree and possible mechanisms of cortical influences on neurons of the lateral geniculate body are discussed.", "contents": "Centrifugal and centripetal connections of the cat visual cortex. In experiments on curarized cats unit responses in the dorsal lateral geniculate body to stimulation of various zones in area 17 of the visual cortex were analyzed. Of all cells tested 69% were found to respond antidromically and 8% orthodromically; in 7.6% of cells IPSPs occurred either after an initial antidromic spike or without it. The velocities of conduction of excitation along the corticopetal fibers of the optic radiation varied from 28 to 4.3 m/sec, but the three commonest groups of fibers had conduction velocities of 28-19, 14-12, and 10-9.5 m/sec. A difference between latent periods of antidromic responses of the same neurons was found to stimulation of different zones of the visual cortex; this indicates that axons of geniculo-cortical fibers split into several branches which form contacts with several neurons in area 17 of the visual cortex. The degree and possible mechanisms of cortical influences on neurons of the lateral geniculate body are discussed."}
{"id": "PMID:213741", "title": "Asynchronous maturation of pathways for impulses from muscle and skin receptors to the sensomotor cortex in rabbits.", "content": "A comparative analysis was undertaken of the functional and structural maturation of peripheral pathways for the conduction of afferent impulses to the sensomotor cortex from muscle and skin receptors of the sciatic nerve during postnatal ontogeny in rabbits. The criterion of functional maturity of the fibers was their sensitivity to the blocking action of procaine when applied to muscular and cutaneous nerves. Structural maturation of peripheral nerve fibers was determined by the degree of their myelination. Successive blocking of fibers of muscular and cutaneous nerves by procaine was shown to depress certain components of the cortical evoked potential. As the animal develops, the sensitivity of its nerve fibers to procaine and the configuration of the evoked response are modified. Different peripheral projections, maturing at different times, participate in the organization of individual components of the cortical evoked potentials. This also takes place during maturation of peripheral afferent projections from muscular and cutaneous receptors.", "contents": "Asynchronous maturation of pathways for impulses from muscle and skin receptors to the sensomotor cortex in rabbits. A comparative analysis was undertaken of the functional and structural maturation of peripheral pathways for the conduction of afferent impulses to the sensomotor cortex from muscle and skin receptors of the sciatic nerve during postnatal ontogeny in rabbits. The criterion of functional maturity of the fibers was their sensitivity to the blocking action of procaine when applied to muscular and cutaneous nerves. Structural maturation of peripheral nerve fibers was determined by the degree of their myelination. Successive blocking of fibers of muscular and cutaneous nerves by procaine was shown to depress certain components of the cortical evoked potential. As the animal develops, the sensitivity of its nerve fibers to procaine and the configuration of the evoked response are modified. Different peripheral projections, maturing at different times, participate in the organization of individual components of the cortical evoked potentials. This also takes place during maturation of peripheral afferent projections from muscular and cutaneous receptors."}
{"id": "PMID:213746", "title": "Multicore disease. Report of a case with lack of fibre type differentiation.", "content": "A six year old boy had congenital hypotonia and nonprogressive proximal muscular weakness, with mild abnormalities in the E. M. G. and normal serum enzyme levels. There was lack of fibre type differentiation in the quadriceps muscle biopsy. The fibres had high oxidative enzyme activity and low ATPase 9.4 activity. In almost every fibre there were multiple areas of focal decrease of oxidative enzyme activity, resembling in few of them the lesion described in Central Core Disease. There was abscence of mitochondria and disorganization of the sarcomere with streaming of the Z line within the lesions. The clinical and histological observations have close similarity to the cases first described by A. G. Engel et al. in 1971 as \"Multicore Diseases\" and to other similar reported cases.", "contents": "Multicore disease. Report of a case with lack of fibre type differentiation. A six year old boy had congenital hypotonia and nonprogressive proximal muscular weakness, with mild abnormalities in the E. M. G. and normal serum enzyme levels. There was lack of fibre type differentiation in the quadriceps muscle biopsy. The fibres had high oxidative enzyme activity and low ATPase 9.4 activity. In almost every fibre there were multiple areas of focal decrease of oxidative enzyme activity, resembling in few of them the lesion described in Central Core Disease. There was abscence of mitochondria and disorganization of the sarcomere with streaming of the Z line within the lesions. The clinical and histological observations have close similarity to the cases first described by A. G. Engel et al. in 1971 as \"Multicore Diseases\" and to other similar reported cases."}
{"id": "PMID:213748", "title": "World Health Organization studies of prostaglandins versus saline as abortifacients. A reappraisal.", "content": "The World Health Organization (WHO) Task Force on the Use of Prostaglandins for the Regulation of Fertility has sponsored a series of randomized clinical trials and case-series investigations to assess the effectiveness and safety of prostaglandins as abortifacients. Our reanalysis of the WHO studies found the prostaglandins to be faster and more hazardour than hypertonic saline as intraamniotic abortifacients. Moreover, studies by the Center for Disease Control imply that dilatation and evacuation (D&E) may be more effective, safe, convenient, and inexpensive than prostaglandins for abortions after 12 weeks' gestation, especially in the 13- to 16-week interval. For gestations of greater than or equal to 17 weeks, the occurrence of live births in prostaglandin-induced abortions has produced serious legal and ethical problems in the United States. Until the effectiveness and safety of other prostaglandins regimen approach that of D&E, we feel that D&E should be the index of comparison against which newer methods of inducing abortion are tested.", "contents": "World Health Organization studies of prostaglandins versus saline as abortifacients. A reappraisal. The World Health Organization (WHO) Task Force on the Use of Prostaglandins for the Regulation of Fertility has sponsored a series of randomized clinical trials and case-series investigations to assess the effectiveness and safety of prostaglandins as abortifacients. Our reanalysis of the WHO studies found the prostaglandins to be faster and more hazardour than hypertonic saline as intraamniotic abortifacients. Moreover, studies by the Center for Disease Control imply that dilatation and evacuation (D&E) may be more effective, safe, convenient, and inexpensive than prostaglandins for abortions after 12 weeks' gestation, especially in the 13- to 16-week interval. For gestations of greater than or equal to 17 weeks, the occurrence of live births in prostaglandin-induced abortions has produced serious legal and ethical problems in the United States. Until the effectiveness and safety of other prostaglandins regimen approach that of D&E, we feel that D&E should be the index of comparison against which newer methods of inducing abortion are tested."}
{"id": "PMID:213749", "title": "[Kaposi sarcoma. A short review on a rare disease].", "content": "Pathological, clinical, epidemiological and immunological aspects of a rare tumor, Kaposi's sarcoma, are briefly discussed. The prevalence of the disease in an African population raises questions about genetic and environmental factors in its carcinogenesis. Immunological data indicate a probable viral origin. The clinical patterns seem to be influenced by alterations of the immune defense mechanisms. Most questions about its biological behaviour remain to be answered yet.", "contents": "[Kaposi sarcoma. A short review on a rare disease]. Pathological, clinical, epidemiological and immunological aspects of a rare tumor, Kaposi's sarcoma, are briefly discussed. The prevalence of the disease in an African population raises questions about genetic and environmental factors in its carcinogenesis. Immunological data indicate a probable viral origin. The clinical patterns seem to be influenced by alterations of the immune defense mechanisms. Most questions about its biological behaviour remain to be answered yet."}
{"id": "PMID:213750", "title": "[5-fluorouracil inhibits the collagenolytic activity of invasive colonic adenocarcinomas in vitro].", "content": "By means of a biological assay for the enzyme collagenase the activity of this protease was examined in 12 invasive adenocarcinomas of the colon. In spite of considerable quantitative differences collagenolytic activity in the dimensions of 10(-3) units/mm theta tissue could be revealed in all cases. EDTA inhibited the reaction by 19%, normal human serum by 23% in the average, whereas 1,10-0-phenanthroline, D-penicillamine as well as the cytostatic 5-fluorouracil resulted in nearly total inhibition. It can be suggested that the activity of the colonic carcinoma is not derived from granulocytes, serum, or normal mucosa, but from the tumor itself. Contrasting to the limited inhibition by normal serum inhibitors, the enzyme is nearly fully inhibited by 5-fluorouracil.", "contents": "[5-fluorouracil inhibits the collagenolytic activity of invasive colonic adenocarcinomas in vitro]. By means of a biological assay for the enzyme collagenase the activity of this protease was examined in 12 invasive adenocarcinomas of the colon. In spite of considerable quantitative differences collagenolytic activity in the dimensions of 10(-3) units/mm theta tissue could be revealed in all cases. EDTA inhibited the reaction by 19%, normal human serum by 23% in the average, whereas 1,10-0-phenanthroline, D-penicillamine as well as the cytostatic 5-fluorouracil resulted in nearly total inhibition. It can be suggested that the activity of the colonic carcinoma is not derived from granulocytes, serum, or normal mucosa, but from the tumor itself. Contrasting to the limited inhibition by normal serum inhibitors, the enzyme is nearly fully inhibited by 5-fluorouracil."}
{"id": "PMID:213751", "title": "Unusual intracytoplasmic inclusions in a case of idiopathic scleritis.", "content": "Large cells containing prominent, refractile PAS-positive inclusions were found in cytological smears prepared from scrapings of the conjunctiva of an elderly diabetic patient with idiopathic scleritis progressing to scleromalacia perforans. Electron-microscopic study of these inclusions revealed them to be intracellular accumulations of dense, flocculent mucoid material within vacuoles whose interior surface was frequently decorated with microvilli. Similar inclusions have been reported in a number of neoplasms in nonocular tissue. The significance of these findings with regard to the patient's condition is not understood.", "contents": "Unusual intracytoplasmic inclusions in a case of idiopathic scleritis. Large cells containing prominent, refractile PAS-positive inclusions were found in cytological smears prepared from scrapings of the conjunctiva of an elderly diabetic patient with idiopathic scleritis progressing to scleromalacia perforans. Electron-microscopic study of these inclusions revealed them to be intracellular accumulations of dense, flocculent mucoid material within vacuoles whose interior surface was frequently decorated with microvilli. Similar inclusions have been reported in a number of neoplasms in nonocular tissue. The significance of these findings with regard to the patient's condition is not understood."}
{"id": "PMID:213752", "title": "Pharyngoconjunctival fever caused by adenovirus type 19.", "content": "A case of laboratory-acquired type 19 adenovirus infection is reported.  The patient showed the classical triad of pharyngitis, acute follicular conjunctivitis and fever. Adenovirus type 19 was isolated from the affected eye, and the infection was confirmed by demonstration of seroconversion to this virus.", "contents": "Pharyngoconjunctival fever caused by adenovirus type 19. A case of laboratory-acquired type 19 adenovirus infection is reported.  The patient showed the classical triad of pharyngitis, acute follicular conjunctivitis and fever. Adenovirus type 19 was isolated from the affected eye, and the infection was confirmed by demonstration of seroconversion to this virus."}
{"id": "PMID:213753", "title": "Observations on the effect of different methods of processing on the bacterial contaminants of bovine and ovine tripe.", "content": "A comparison was made of the multiplication of bacteria in specimens of tripe processed in different ways. There was little difference in this respect between commercial tripe as offered for purchase to the consumer and rough and scraped tripe incubated at 30 degrees C for 24 h. Tripe stored at 4 degrees C or in acetic acid (pH 4) at 30 degrees C for 24 h, however, had appreciably fewer bacteria.", "contents": "Observations on the effect of different methods of processing on the bacterial contaminants of bovine and ovine tripe. A comparison was made of the multiplication of bacteria in specimens of tripe processed in different ways. There was little difference in this respect between commercial tripe as offered for purchase to the consumer and rough and scraped tripe incubated at 30 degrees C for 24 h. Tripe stored at 4 degrees C or in acetic acid (pH 4) at 30 degrees C for 24 h, however, had appreciably fewer bacteria."}
{"id": "PMID:213754", "title": "Clinical, histologic, cytologic, and ultrastructural characteristics of the oral lesions from hereditary mucoepithelial dysplasia. A disease of gap junction and desmosome formation.", "content": "Hereditary mucoepithelial dysplasia is an autosomal, dominantly inherited disorder affecting all of the orificial mucosa with cataracts, follicular keratosis of skin, nonscarring alopecia, bouts of pneumonia, spontaneous pneumothorax, and terminal cor pulmonale. The oral lesion is a fiery red, flat or micropapillary-appearing mucosa most frequently involving the gingiva and hard palate. All oral and pharyngeal mucosa may be involved, however. Red scrotal mucosa of the tongue is common. Histologically, the oral mucosa shows a lack of cornified and keratinized cells, a decrease in the thickness of the epithelial cell layer, dyshesion, and dyskeratosis. Papanicolaou smears show lack of epithelial cell maturation, poikilocytosis, anisocytosis, large paranuclear cytoplasmic vacuoles, and cytoplasmic strand-shaped inclusions. Ultrastructural features include a paucity of desmosomes, intercellular accumulations of amorphous material, cytoplasmic vacuoles, and paranuclear lesions with strands of material resembling gap junctions and desmosomes. The condition most likely represents a basic defect in gap junction and desmosome formation.", "contents": "Clinical, histologic, cytologic, and ultrastructural characteristics of the oral lesions from hereditary mucoepithelial dysplasia. A disease of gap junction and desmosome formation. Hereditary mucoepithelial dysplasia is an autosomal, dominantly inherited disorder affecting all of the orificial mucosa with cataracts, follicular keratosis of skin, nonscarring alopecia, bouts of pneumonia, spontaneous pneumothorax, and terminal cor pulmonale. The oral lesion is a fiery red, flat or micropapillary-appearing mucosa most frequently involving the gingiva and hard palate. All oral and pharyngeal mucosa may be involved, however. Red scrotal mucosa of the tongue is common. Histologically, the oral mucosa shows a lack of cornified and keratinized cells, a decrease in the thickness of the epithelial cell layer, dyshesion, and dyskeratosis. Papanicolaou smears show lack of epithelial cell maturation, poikilocytosis, anisocytosis, large paranuclear cytoplasmic vacuoles, and cytoplasmic strand-shaped inclusions. Ultrastructural features include a paucity of desmosomes, intercellular accumulations of amorphous material, cytoplasmic vacuoles, and paranuclear lesions with strands of material resembling gap junctions and desmosomes. The condition most likely represents a basic defect in gap junction and desmosome formation."}
{"id": "PMID:213755", "title": "Odontodysplasia. Report of three cases with vascular nevi overlying the adjacent skin of the face.", "content": "Three cases of odontodysplasia are described, and the literature is reviewed with reference to proposed etiologic mechanisms underlying the pathogenesis of the disorder. The distribution of affected teeth in all four quadrants of one patient is offered as evidence against a somatic mutation as an etiologic mechanism. As infants all three patients had vascular nevi in the facial skin overlying the area where defective teeth developed. Three cases from the literature involved similar vascular lesions. Hypoplastic teeth radiographically similar to odontodysplastic teeth occur in the linear sebaceous nevus syndrome. These findings strongly suggest that local vascular defects are involved in the pathogenesis of odontodysplasia.", "contents": "Odontodysplasia. Report of three cases with vascular nevi overlying the adjacent skin of the face. Three cases of odontodysplasia are described, and the literature is reviewed with reference to proposed etiologic mechanisms underlying the pathogenesis of the disorder. The distribution of affected teeth in all four quadrants of one patient is offered as evidence against a somatic mutation as an etiologic mechanism. As infants all three patients had vascular nevi in the facial skin overlying the area where defective teeth developed. Three cases from the literature involved similar vascular lesions. Hypoplastic teeth radiographically similar to odontodysplastic teeth occur in the linear sebaceous nevus syndrome. These findings strongly suggest that local vascular defects are involved in the pathogenesis of odontodysplasia."}
{"id": "PMID:213756", "title": "Pathologic fractures of the mandible following invasive oral carcinomas.", "content": "Invasive and metastatic oral carcinomas can and often do result in pathologic fractures of the facial bones. Three cases of invasive oral carcinomas resulting in fractures of the mandible have been reported. It was only after multiple-view radiographs that pathologic fractures could be identified. It is mandatory that dental practitioners avail themselves of the radiographic views which assist in establishing a diagnosis. In addition, the role of the dental profession in diagnosing primary and secondary oral carcinomas cannot be overemphasized.", "contents": "Pathologic fractures of the mandible following invasive oral carcinomas. Invasive and metastatic oral carcinomas can and often do result in pathologic fractures of the facial bones. Three cases of invasive oral carcinomas resulting in fractures of the mandible have been reported. It was only after multiple-view radiographs that pathologic fractures could be identified. It is mandatory that dental practitioners avail themselves of the radiographic views which assist in establishing a diagnosis. In addition, the role of the dental profession in diagnosing primary and secondary oral carcinomas cannot be overemphasized."}
{"id": "PMID:213761", "title": "Extraosseous tumor uptake of 99m technetium phosphate compounds in children with abdominal neuroblastoma.", "content": "Sixteen patients with abdominal neuroblastoma had 99m Technetium Phosphate Compounds (99m TC-PC) bone scans as a preoperative evaluation for metastatic disease. Ten patients (62%) had extraosseous tumor uptake while six patients (38%) did not. There was no difference in the incidence of tumor calcification, tumor necrosis or hydronephrosis in the two groups. However, VMA levels were significantly higher in the group with extraosseous tumor uptake. Various bone seeking radionuclides are compared to 99m TC-PC and possible mechanism for extraosseous uptake of such radionuclides are postulated. Awareness of the frequency of such uptake should reduce the possibility of errors in the interpretation of bone scans in patients with neuroblastoma.", "contents": "Extraosseous tumor uptake of 99m technetium phosphate compounds in children with abdominal neuroblastoma. Sixteen patients with abdominal neuroblastoma had 99m Technetium Phosphate Compounds (99m TC-PC) bone scans as a preoperative evaluation for metastatic disease. Ten patients (62%) had extraosseous tumor uptake while six patients (38%) did not. There was no difference in the incidence of tumor calcification, tumor necrosis or hydronephrosis in the two groups. However, VMA levels were significantly higher in the group with extraosseous tumor uptake. Various bone seeking radionuclides are compared to 99m TC-PC and possible mechanism for extraosseous uptake of such radionuclides are postulated. Awareness of the frequency of such uptake should reduce the possibility of errors in the interpretation of bone scans in patients with neuroblastoma."}
{"id": "PMID:213762", "title": "Hypercholesterolemia and hyper-alpha-lipoproteinemia in schoolchildren.", "content": "Elevated levels of high-density lipoprotein cholesterol (C-HDL) can explain apparent hypercholesterolemia in some children, and high C-HDL levels may aggregate in families. In this study, 17 kindreds were identified by virture of hypercholesterolemic proband children whose hypercholesterolemia was accounted for the elevated C-HDL levels Family lipod and lipoprotein sampling revealed three-generation vertical appearance of elevated C-HDL level in two kindreds, and two-generation vertical appearance in eight additional kindreds. Since CHDL level is inversely associated with coronary heart disease in adults, it is important to quantitate C-HDL and low-density lipoprotein cholesterol (C-LDL) in hypercholesterolemic children and to identify those with putatively reduced risk (elevated C-HDL level) or increased risk (elevated C-LDL level).", "contents": "Hypercholesterolemia and hyper-alpha-lipoproteinemia in schoolchildren. Elevated levels of high-density lipoprotein cholesterol (C-HDL) can explain apparent hypercholesterolemia in some children, and high C-HDL levels may aggregate in families. In this study, 17 kindreds were identified by virture of hypercholesterolemic proband children whose hypercholesterolemia was accounted for the elevated C-HDL levels Family lipod and lipoprotein sampling revealed three-generation vertical appearance of elevated C-HDL level in two kindreds, and two-generation vertical appearance in eight additional kindreds. Since CHDL level is inversely associated with coronary heart disease in adults, it is important to quantitate C-HDL and low-density lipoprotein cholesterol (C-LDL) in hypercholesterolemic children and to identify those with putatively reduced risk (elevated C-HDL level) or increased risk (elevated C-LDL level)."}
{"id": "PMID:213759", "title": "Discrepant cortisol values: comparison of radioimmunoassay and competitive protein binding technics.", "content": "Radioimmunoassays are expected to yield precise values representing the antigen, i.e., insulin, growth, cortisol, etc. employed in producing the antibody. However, in a recent study of a synthetic ACTH which involved the measurement of cortisol levels (1), we found that above 20gamma%, the radioimmunoassay (RIA) yields cortisol values distinctly above those obtained with the competitive protein binding (CPB) technic. We now suggest a possible explanation for this discrepancy and have calculated a correction factor.", "contents": "Discrepant cortisol values: comparison of radioimmunoassay and competitive protein binding technics. Radioimmunoassays are expected to yield precise values representing the antigen, i.e., insulin, growth, cortisol, etc. employed in producing the antibody. However, in a recent study of a synthetic ACTH which involved the measurement of cortisol levels (1), we found that above 20gamma%, the radioimmunoassay (RIA) yields cortisol values distinctly above those obtained with the competitive protein binding (CPB) technic. We now suggest a possible explanation for this discrepancy and have calculated a correction factor."}
{"id": "PMID:213764", "title": "Growth deceleration patterns in children with constitutional short stature: an aid to diagnosis.", "content": "A retrospective study of 263 children referred for evaluation of short stature revealed that 149 (56.7%) had constitutional short stature (CSS). A typical pattern of growth was observed in these children. As exemplified by 12 children who had complete serial growth measurements, exaggerated growth deceleration first became apparent between 3 and 6 months of age, was greatest in the first two years of life, and resulted in these children falling more than 2 SDs below the mean for height by 3 years of age. After 3 years of age, the growth rate of these children with CSS was essentially the same as that of normal children, and they ran parallel to the growth curve though below the third percentile. The importance of serial measurements and the growth chart is emphasized, and recommendations are made for the evaluation of short stature or abnormal growth deceleration in the first three years of life. Awareness of this typical pattern of growth in children without disease may aid the pediatrician in his evaluation of short stature and allow for watchful waiting when results of screening tests are normal.", "contents": "Growth deceleration patterns in children with constitutional short stature: an aid to diagnosis. A retrospective study of 263 children referred for evaluation of short stature revealed that 149 (56.7%) had constitutional short stature (CSS). A typical pattern of growth was observed in these children. As exemplified by 12 children who had complete serial growth measurements, exaggerated growth deceleration first became apparent between 3 and 6 months of age, was greatest in the first two years of life, and resulted in these children falling more than 2 SDs below the mean for height by 3 years of age. After 3 years of age, the growth rate of these children with CSS was essentially the same as that of normal children, and they ran parallel to the growth curve though below the third percentile. The importance of serial measurements and the growth chart is emphasized, and recommendations are made for the evaluation of short stature or abnormal growth deceleration in the first three years of life. Awareness of this typical pattern of growth in children without disease may aid the pediatrician in his evaluation of short stature and allow for watchful waiting when results of screening tests are normal."}
{"id": "PMID:213760", "title": "Comparisons of synthetic 1-18 ACTH (Organon 2001) and 1-39 ACTH of animal origin in human subjects.", "content": "The studies in human subjects herein reported provide data on the relative effects of 1-18 ACTH (Organon 2001) and commercial 1-39 ACTH of animal origin on plasma cortisol, serum non-esterified fatty acids, and certain urinary steroids.", "contents": "Comparisons of synthetic 1-18 ACTH (Organon 2001) and 1-39 ACTH of animal origin in human subjects. The studies in human subjects herein reported provide data on the relative effects of 1-18 ACTH (Organon 2001) and commercial 1-39 ACTH of animal origin on plasma cortisol, serum non-esterified fatty acids, and certain urinary steroids."}
{"id": "PMID:213768", "title": "[A simple device for cultivation of anaerobic bacteria (author's transl)].", "content": "A new concept for isolation and enumeration of anaerobic bacteria in food is presented. The sample is collected and diluted under anaerobic conditions in a specially designed syringe (M.O.S.), in which cultivation also takes place. A comparison between this method and cultivation in anaerobic jars (GasPak) from a common inoculum revealed a higher number of Clostridium perfringens with the M.O.S.-technique.", "contents": "[A simple device for cultivation of anaerobic bacteria (author's transl)]. A new concept for isolation and enumeration of anaerobic bacteria in food is presented. The sample is collected and diluted under anaerobic conditions in a specially designed syringe (M.O.S.), in which cultivation also takes place. A comparison between this method and cultivation in anaerobic jars (GasPak) from a common inoculum revealed a higher number of Clostridium perfringens with the M.O.S.-technique."}
{"id": "PMID:213769", "title": "Hypervitaminosis D in fur-bearing animals.", "content": "Investigations concerning the effect on fur-bearing animals of large doses of vitamin D3 were carried out. The material comprised 62 animals in all--10 silver foxes, 17 blue foxes and 35 mink (Table II). Daily doses of 5 IU vitamin D3/g body weight for two months did not produce clinical symptoms in the foxes. However, a short while after the dose was increased to 10 IU, the animals showed loss of appetite, had difficulty in moving, were apathetic and developed dark coloured faeces. Analysis of blood serum showed markedly raised calcium values (Table III). Calcium deposits were demonstrated in the kidneys and in some cases also in the musculature, gastric mucosa, bronchi and the larger blood vessels. No abnormal signs were shown by 30 mink which received 0.6--0.7 IU vitamin D3/g body weight for five months. PM findings were normal.", "contents": "Hypervitaminosis D in fur-bearing animals. Investigations concerning the effect on fur-bearing animals of large doses of vitamin D3 were carried out. The material comprised 62 animals in all--10 silver foxes, 17 blue foxes and 35 mink (Table II). Daily doses of 5 IU vitamin D3/g body weight for two months did not produce clinical symptoms in the foxes. However, a short while after the dose was increased to 10 IU, the animals showed loss of appetite, had difficulty in moving, were apathetic and developed dark coloured faeces. Analysis of blood serum showed markedly raised calcium values (Table III). Calcium deposits were demonstrated in the kidneys and in some cases also in the musculature, gastric mucosa, bronchi and the larger blood vessels. No abnormal signs were shown by 30 mink which received 0.6--0.7 IU vitamin D3/g body weight for five months. PM findings were normal."}
{"id": "PMID:213773", "title": "Plasma lipoprotein separations by zonal ultracentrifugation.", "content": "Procedures for the separation of plasma lipoprotein classes and subclasses by zonal ultracentrifugation are described. The main density classes, very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL), in plasma can be separated in a single run for 20 hours. For the isolation of VLDL-LDL a centrifugation time of only 90 minutes is needed. Separations can be performed on plasma volumes varying from 10 to 400 ml in the Ti-14 rotor used; VLDL can in this way be isolated from 400 ml plasma in 30 minutes. The advantages and disadvantages of zonal ultracentrifugation in comparison with the commonly employed differential ultracentrifugation for separation of lipoproteins are discussed.", "contents": "Plasma lipoprotein separations by zonal ultracentrifugation. Procedures for the separation of plasma lipoprotein classes and subclasses by zonal ultracentrifugation are described. The main density classes, very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL), in plasma can be separated in a single run for 20 hours. For the isolation of VLDL-LDL a centrifugation time of only 90 minutes is needed. Separations can be performed on plasma volumes varying from 10 to 400 ml in the Ti-14 rotor used; VLDL can in this way be isolated from 400 ml plasma in 30 minutes. The advantages and disadvantages of zonal ultracentrifugation in comparison with the commonly employed differential ultracentrifugation for separation of lipoproteins are discussed."}
{"id": "PMID:213774", "title": "Lipoproteins removed from serum and plasma by membrane filtration.", "content": "Tangential (crossflow) filtration of a plasma/serum mixture through 0.2 micrometer-poresize polycarbonate track-etch membrane filters (PC) at pressures less than 10 psi removes low density lipoproteins (LDL) and very low density lipoproteins (VLDL) but not high density lipoproteins (HDL) from the filtrate. At pressures greater than 10 psi all lipoproteins pass through the PC. Once the filters have been intruded with LDL and VLDL those lipoproteins continue to pass the filters despite subsequent reduction in differential pressure below 10 psi.", "contents": "Lipoproteins removed from serum and plasma by membrane filtration. Tangential (crossflow) filtration of a plasma/serum mixture through 0.2 micrometer-poresize polycarbonate track-etch membrane filters (PC) at pressures less than 10 psi removes low density lipoproteins (LDL) and very low density lipoproteins (VLDL) but not high density lipoproteins (HDL) from the filtrate. At pressures greater than 10 psi all lipoproteins pass through the PC. Once the filters have been intruded with LDL and VLDL those lipoproteins continue to pass the filters despite subsequent reduction in differential pressure below 10 psi."}
{"id": "PMID:213775", "title": "A modified procedure for the purification of clostridial collagenase.", "content": "A method is described for the purification of clostridial collagenase from a crude enzyme preparation employing cation exchange chromatography on SP Sephadex, anion exchange chromatography on DEAE cellulose and gel filtration on Sephacryl S-200. Emphasis was placed on purity using continuous shallow gradients for the ion exchange separations to increase resolution and monitoring eluates both with respect to ultraviolet light absorption at 230 nm and analytical disc gel acrylamide electrophoresis. In addition, protein fractions were assayed for collagenolytic and non-specific proteolytic activity. The purity of the final preparation was assessed by acrylamide electrophoresis, gel filtration and amino acid analysis. The isolated enzyme hydrolyzed between 30 and 40% of rat tail tendon collagen in 1 h at 37 degrees C and lacked measurable trypsin or elastase-like activity.", "contents": "A modified procedure for the purification of clostridial collagenase. A method is described for the purification of clostridial collagenase from a crude enzyme preparation employing cation exchange chromatography on SP Sephadex, anion exchange chromatography on DEAE cellulose and gel filtration on Sephacryl S-200. Emphasis was placed on purity using continuous shallow gradients for the ion exchange separations to increase resolution and monitoring eluates both with respect to ultraviolet light absorption at 230 nm and analytical disc gel acrylamide electrophoresis. In addition, protein fractions were assayed for collagenolytic and non-specific proteolytic activity. The purity of the final preparation was assessed by acrylamide electrophoresis, gel filtration and amino acid analysis. The isolated enzyme hydrolyzed between 30 and 40% of rat tail tendon collagen in 1 h at 37 degrees C and lacked measurable trypsin or elastase-like activity."}
{"id": "PMID:213788", "title": "ACTH, but not corticosterone impairs habituation and reduces exploration.", "content": "The habituation of an orienting response to auditory stimuli was impaired in rats by the administration of ACTH1-24. This impairment is unlikely to be due to the action of corticosterone because of the time course of the effect, because injected corticosterone had no effect on hibituation and because the peptide fragment ACTH4-10, which does not release corticosterone, also impaired habituation. Both ACTH1-24 and ACTH4-10 reduced the level of exploration measured in a holeboard, but corticosterone had no significant effect. However ACTH did not impair habituation and exploration, thus providing further evidence that there are different mechanisms underlying habituation of orienting and habituation of exploration.", "contents": "ACTH, but not corticosterone impairs habituation and reduces exploration. The habituation of an orienting response to auditory stimuli was impaired in rats by the administration of ACTH1-24. This impairment is unlikely to be due to the action of corticosterone because of the time course of the effect, because injected corticosterone had no effect on hibituation and because the peptide fragment ACTH4-10, which does not release corticosterone, also impaired habituation. Both ACTH1-24 and ACTH4-10 reduced the level of exploration measured in a holeboard, but corticosterone had no significant effect. However ACTH did not impair habituation and exploration, thus providing further evidence that there are different mechanisms underlying habituation of orienting and habituation of exploration."}
{"id": "PMID:213790", "title": "Drinking in water deprived rats after combined central angiotensin receptor and converting enzyme blockade.", "content": "Saralasin, an angiotensin II receptor antagonist, is ineffective in reducing drinking after water-deprivation (WD). Angiotensin III has considerable dipsogenic potency. It may be formed without angiotensin II as an intermediate. To clarify whether angiotensin III formation masks a role for angiotensin in WD, 48 hr WD rats were infused via a lateral cerebroventricle with a) CSF, b) Saralasin, c) SQ 20,881, a converting enzyme inhibitor, or d) Saralasin + SQ. No drug effect on drinking was observed. The results demonstrate that angiotensin III is not required for WD drinking.", "contents": "Drinking in water deprived rats after combined central angiotensin receptor and converting enzyme blockade. Saralasin, an angiotensin II receptor antagonist, is ineffective in reducing drinking after water-deprivation (WD). Angiotensin III has considerable dipsogenic potency. It may be formed without angiotensin II as an intermediate. To clarify whether angiotensin III formation masks a role for angiotensin in WD, 48 hr WD rats were infused via a lateral cerebroventricle with a) CSF, b) Saralasin, c) SQ 20,881, a converting enzyme inhibitor, or d) Saralasin + SQ. No drug effect on drinking was observed. The results demonstrate that angiotensin III is not required for WD drinking."}
{"id": "PMID:213794", "title": "Ultraviolet-induced thermoluminescence and phosphorescence in Mg2SiO4:Tb.", "content": "Among the common TLD materials studied (Mg2SiO4:Tb, Al2O3:Si, Ti, CaSO4:Tm, CaSO4:Dy, Li2B4O7:Mn and LiF TLD-100), Mg2SiO4:Tb was found to have the highest intrinsic TL sensitivity to UV radiation (wavelength 253.7 nm). The TL response of the dosimetric peak (approximately 200 degrees C) of virgin Mg2SiO4:Tb was studied as a function of UV exposure in the range 10--10(4) J m-2. The UV-induced TL was not affected by room-light and no appreciable fading was observed up to 20 days after irradiation indicating that this is a promising TL phosphor for UV dosimetry. The UV sensitivity was found to increase with increasing preliminary gamma exposure above 10(-2)Ckg-1 (after a post-irradiation anneal at 300 degrees C for 1 h). The degree of sensitisation was found proportional to the intensity of the residual TL peak at 450 degrees C. A study of the TL response of the sensitised sample as a function of UV test exposure has demonstrated the transfer of charge carriers from the deep traps to the dosimetry traps. Both virgin and gamma-exposed Mg2SiO4:Tb were found to exhigit phosphorescence decay at room temperature after UV stimulation. The intensity of the UV stimulated phosphorescence was found to increase with the gamma exposure above 10(-2) C kg-1.", "contents": "Ultraviolet-induced thermoluminescence and phosphorescence in Mg2SiO4:Tb. Among the common TLD materials studied (Mg2SiO4:Tb, Al2O3:Si, Ti, CaSO4:Tm, CaSO4:Dy, Li2B4O7:Mn and LiF TLD-100), Mg2SiO4:Tb was found to have the highest intrinsic TL sensitivity to UV radiation (wavelength 253.7 nm). The TL response of the dosimetric peak (approximately 200 degrees C) of virgin Mg2SiO4:Tb was studied as a function of UV exposure in the range 10--10(4) J m-2. The UV-induced TL was not affected by room-light and no appreciable fading was observed up to 20 days after irradiation indicating that this is a promising TL phosphor for UV dosimetry. The UV sensitivity was found to increase with increasing preliminary gamma exposure above 10(-2)Ckg-1 (after a post-irradiation anneal at 300 degrees C for 1 h). The degree of sensitisation was found proportional to the intensity of the residual TL peak at 450 degrees C. A study of the TL response of the sensitised sample as a function of UV test exposure has demonstrated the transfer of charge carriers from the deep traps to the dosimetry traps. Both virgin and gamma-exposed Mg2SiO4:Tb were found to exhigit phosphorescence decay at room temperature after UV stimulation. The intensity of the UV stimulated phosphorescence was found to increase with the gamma exposure above 10(-2) C kg-1."}
{"id": "PMID:213795", "title": "Impaired renal prostaglandin E2 biosynthesis in human hypertensive states.", "content": "Urinary Prostaglandin E2 (PGE2), a known indicator of renal production, was measured by specific radioimmunoassay in 111 normal volunteers, 85 patients with essential hypertension, 6 with renovascular hypertension, and 23 patients with primary aldosteronism. Women excreted less PGE2 than men in both normotensive and hypertensive groups. When compared to normals, essential hypertensives demonstrated significantly lower PGE2 levels, with one third excreting less than 100 ng/24 hr, values usually seen only in subjects receiving the prostaglandin synthetase inhibitor, indomethacin. Normal PGE2 was seen in patients with renovascular hypertension, and levels were uninfluenced by treatment with the converting enzyme inhibitor SQ14225, Despite normalization of blood pressure and increased plasma renin activity. Normal PGE2 was also encountered in primary aldosteronism. These data indicate that impaired renal PGE2 biosynthesis is specific for human essential hypertension, and is not secondary to the elevated blood pressure. Although PGE2 excretion tends to be lower in low-renin hypertension, a constant relationship between PGE2 and renin is not always apparent.", "contents": "Impaired renal prostaglandin E2 biosynthesis in human hypertensive states. Urinary Prostaglandin E2 (PGE2), a known indicator of renal production, was measured by specific radioimmunoassay in 111 normal volunteers, 85 patients with essential hypertension, 6 with renovascular hypertension, and 23 patients with primary aldosteronism. Women excreted less PGE2 than men in both normotensive and hypertensive groups. When compared to normals, essential hypertensives demonstrated significantly lower PGE2 levels, with one third excreting less than 100 ng/24 hr, values usually seen only in subjects receiving the prostaglandin synthetase inhibitor, indomethacin. Normal PGE2 was seen in patients with renovascular hypertension, and levels were uninfluenced by treatment with the converting enzyme inhibitor SQ14225, Despite normalization of blood pressure and increased plasma renin activity. Normal PGE2 was also encountered in primary aldosteronism. These data indicate that impaired renal PGE2 biosynthesis is specific for human essential hypertension, and is not secondary to the elevated blood pressure. Although PGE2 excretion tends to be lower in low-renin hypertension, a constant relationship between PGE2 and renin is not always apparent."}
{"id": "PMID:213796", "title": "Effects of cervical sympathetic ganglionectomy on cyclic-AMP and prostaglandins in brain and eye tissues and fluids.", "content": "Studies were conducted confirming supersensitivity to catecholamines on intraocular pressure and pupil size following bilateral superior cervical ganglionectomy in rabbits. At the termination of these studies we examined changes in cyclic adenylic acid and prostaglandin content in jugular vein effluent and various brain and ocular tissues and fluids of the sympathectomized versus control animals. In the blood effluent we found significant elevation of cyclic adenylic acid and significant lowering of prostaglandin F1alpha in the sympathectomized animals. Although we found elevation of prostaglandin in certain tissues of the sympathectomized animals, there were no significant changes in cyclic adenylic acid levels between sympathectomized and control animals in the tissues examined. The findings of prostaglandin (blood and tissue) and cyclic adenylic acid (blood) changes in sympathectomized animals, associated with known changes in intraocular pressure and pupil size (due to catecholamine supersensitivity) must elicit further interest in the correlation and interpretation of various other central physiological and metabolic events in cervical sympathectomized animals.", "contents": "Effects of cervical sympathetic ganglionectomy on cyclic-AMP and prostaglandins in brain and eye tissues and fluids. Studies were conducted confirming supersensitivity to catecholamines on intraocular pressure and pupil size following bilateral superior cervical ganglionectomy in rabbits. At the termination of these studies we examined changes in cyclic adenylic acid and prostaglandin content in jugular vein effluent and various brain and ocular tissues and fluids of the sympathectomized versus control animals. In the blood effluent we found significant elevation of cyclic adenylic acid and significant lowering of prostaglandin F1alpha in the sympathectomized animals. Although we found elevation of prostaglandin in certain tissues of the sympathectomized animals, there were no significant changes in cyclic adenylic acid levels between sympathectomized and control animals in the tissues examined. The findings of prostaglandin (blood and tissue) and cyclic adenylic acid (blood) changes in sympathectomized animals, associated with known changes in intraocular pressure and pupil size (due to catecholamine supersensitivity) must elicit further interest in the correlation and interpretation of various other central physiological and metabolic events in cervical sympathectomized animals."}
{"id": "PMID:213797", "title": "Evidence for H2O2 mediating the irreversible action of acetylenic inhibitors of prostaglandin biosynthesis.", "content": "Oxidizing intermediates formed during prostaglandin biosynthesis can be detected by ferrocytochrome c and epinephrine. Different intermediates were responsible for the oxidative colorimetric changes with epinephrine and ferrocytochrome c, and submicromolar amounts of oxidant were detectable. Catalase diminished the absorbance change with epinephrine, but it did not stop the conversion of arachidonate to prostaglandins. This result indicates that small amounts of H2O2 were formed when producing the colorimetric change, and these had no apparent effect upon the enzyme stability. No colorimetric changes were detected during the time-dependent loss of oxygenase activity caused by various acetylenic acids, indicating that negligible amounts of H2O2 were formed. Nevertheless, the destructive action of the acetylenic acid was prevented by catalase, and it thereby appeared due to small amounts of H2O2 generated in situ as a result of a metastable complex of enzyme, oxygen and the acetylenic substrate analog.", "contents": "Evidence for H2O2 mediating the irreversible action of acetylenic inhibitors of prostaglandin biosynthesis. Oxidizing intermediates formed during prostaglandin biosynthesis can be detected by ferrocytochrome c and epinephrine. Different intermediates were responsible for the oxidative colorimetric changes with epinephrine and ferrocytochrome c, and submicromolar amounts of oxidant were detectable. Catalase diminished the absorbance change with epinephrine, but it did not stop the conversion of arachidonate to prostaglandins. This result indicates that small amounts of H2O2 were formed when producing the colorimetric change, and these had no apparent effect upon the enzyme stability. No colorimetric changes were detected during the time-dependent loss of oxygenase activity caused by various acetylenic acids, indicating that negligible amounts of H2O2 were formed. Nevertheless, the destructive action of the acetylenic acid was prevented by catalase, and it thereby appeared due to small amounts of H2O2 generated in situ as a result of a metastable complex of enzyme, oxygen and the acetylenic substrate analog."}
{"id": "PMID:213798", "title": "The solitary pulmonary nodule.", "content": "Although most asymptomatic solitary pulmonary nodules are benign, many are truly malignant. Age of the patient, history of antecedent infection or industrial exposure, and radiographic appearance and behavior are helpful in establishing the diagnosis. Invasive techniques and their indications are discussed as well as some of the growth characteristics of potentially malignant lesions.", "contents": "The solitary pulmonary nodule. Although most asymptomatic solitary pulmonary nodules are benign, many are truly malignant. Age of the patient, history of antecedent infection or industrial exposure, and radiographic appearance and behavior are helpful in establishing the diagnosis. Invasive techniques and their indications are discussed as well as some of the growth characteristics of potentially malignant lesions."}
{"id": "PMID:213799", "title": "Occupational lung disease.", "content": "Occupational lung diseases can be conveniently classified into disorders of the airways, the alveoli, and the lung interstitium. Diseases of each category have a distinct clinical and pathologic presentation despite diverse causes.", "contents": "Occupational lung disease. Occupational lung diseases can be conveniently classified into disorders of the airways, the alveoli, and the lung interstitium. Diseases of each category have a distinct clinical and pathologic presentation despite diverse causes."}
{"id": "PMID:213800", "title": "Patients with tracheostomies: goals of management.", "content": "Care of the patient with tracheostomy is not difficult if care is taken to define clearly the needs of the particular patient. An awareness of the goals of care, daily maintenance, and possible complications is necessary to successful management.", "contents": "Patients with tracheostomies: goals of management. Care of the patient with tracheostomy is not difficult if care is taken to define clearly the needs of the particular patient. An awareness of the goals of care, daily maintenance, and possible complications is necessary to successful management."}
{"id": "PMID:213811", "title": "Determination of the crystalline fraction in bone and other mineralizing tissues within the histochemical range by electron spin resonance spectroscopy.", "content": "The theoretical principle based on the application of electron spin resonance technique for calculation of the crystallinity coefficient of mineralized tissues is presented. The method is based on measurements of radiation-induced stable paramagnetic centres derived from the crystalline fraction of tissue mineral. The high sensitivity and accuracy of the discussed method allows to apply it in the histochemical range.", "contents": "Determination of the crystalline fraction in bone and other mineralizing tissues within the histochemical range by electron spin resonance spectroscopy. The theoretical principle based on the application of electron spin resonance technique for calculation of the crystallinity coefficient of mineralized tissues is presented. The method is based on measurements of radiation-induced stable paramagnetic centres derived from the crystalline fraction of tissue mineral. The high sensitivity and accuracy of the discussed method allows to apply it in the histochemical range."}
{"id": "PMID:213820", "title": "[Technics of measuring the motive force of very small ameboid cells].", "content": "A technic have been perfected which measures directly the motive force of very small ameboid cells and indicates the tropism of the amoeba. By using this technic, the motive force of Entamoeba histolytica was measured. It varied between +/- 1.5 x 10-4 dyne. We have also shown chimiotactism in Entamoeba histolytica. The metabolic coumpound excreted by this cell induced negative tropism.", "contents": "[Technics of measuring the motive force of very small ameboid cells]. A technic have been perfected which measures directly the motive force of very small ameboid cells and indicates the tropism of the amoeba. By using this technic, the motive force of Entamoeba histolytica was measured. It varied between +/- 1.5 x 10-4 dyne. We have also shown chimiotactism in Entamoeba histolytica. The metabolic coumpound excreted by this cell induced negative tropism."}
{"id": "PMID:213827", "title": "[Long-term treatment with corticoids in respiratory disorders].", "content": "In a first chapter the author reviews the mechanisms of action of corticoids in respiratory diseases. Moreover the causes and the prevalence of unwanted side-effects are discussed. The advantages of synthetic glucocorticoids with short half-life time in pneumology are stressed. In the following chapters, the rationale of long-term corticoid treatments of asthma, in non allergic obstructive chronic lung diseases, in sarcoidosis and in the thoracic localisations of some collagen diseases is presented in detail. Regarding the treatment of asthma the author discusses the advantages of the alternate-day therapy, the use of corticoids in aerosols and the ratioale of ACTH. The usefulness of alternate-day therapy in sarcoidosis is also advocated.", "contents": "[Long-term treatment with corticoids in respiratory disorders]. In a first chapter the author reviews the mechanisms of action of corticoids in respiratory diseases. Moreover the causes and the prevalence of unwanted side-effects are discussed. The advantages of synthetic glucocorticoids with short half-life time in pneumology are stressed. In the following chapters, the rationale of long-term corticoid treatments of asthma, in non allergic obstructive chronic lung diseases, in sarcoidosis and in the thoracic localisations of some collagen diseases is presented in detail. Regarding the treatment of asthma the author discusses the advantages of the alternate-day therapy, the use of corticoids in aerosols and the ratioale of ACTH. The usefulness of alternate-day therapy in sarcoidosis is also advocated."}
{"id": "PMID:213828", "title": "Epidemiology of cytomegalovirus infections during pregnancy and infancy. A prospective study.", "content": "The occurrence and possible consequences of cytomegalovirus (CMV) infections were studied in 200 mothers and their children by means of immunofluorescent antibody assays in serum, virus isolation from urine and regular clinical and neurological examinations. The prospective study covered the time from early pregnancy to 1 year post partum. The frequency of intrauterine infections was 2%, while 30% of the children became perinatally infected as indicated by the onset of virus excretion and an antibody response at the age of 2--4 months. Later on the occurrence of CMV infections declined sharply. 23 mothers had no CMV antibodies and none of their children contracted CMV during the first year of life. Maternal antibodies seemed unable to protect the child from CMV infections or to delay the onset of virus excretion in perinatally infected children. Intrauterine infections did not correlate with significant increases in the antibodiy titres of the mothers or the presence of IgM antibodies either in the mother's sera or in the cord sera. Perinatal infections were often associated with the presence of IgM antibodies both in the child and in the mother and in these mothers significant increases in CMV antibody titres were frequently seen, probably indicating an activated latent infection. Immunofluorescent antibody assay correlated well with virus isolations and was more sensitive than complement-fixing antibody assay.", "contents": "Epidemiology of cytomegalovirus infections during pregnancy and infancy. A prospective study. The occurrence and possible consequences of cytomegalovirus (CMV) infections were studied in 200 mothers and their children by means of immunofluorescent antibody assays in serum, virus isolation from urine and regular clinical and neurological examinations. The prospective study covered the time from early pregnancy to 1 year post partum. The frequency of intrauterine infections was 2%, while 30% of the children became perinatally infected as indicated by the onset of virus excretion and an antibody response at the age of 2--4 months. Later on the occurrence of CMV infections declined sharply. 23 mothers had no CMV antibodies and none of their children contracted CMV during the first year of life. Maternal antibodies seemed unable to protect the child from CMV infections or to delay the onset of virus excretion in perinatally infected children. Intrauterine infections did not correlate with significant increases in the antibodiy titres of the mothers or the presence of IgM antibodies either in the mother's sera or in the cord sera. Perinatal infections were often associated with the presence of IgM antibodies both in the child and in the mother and in these mothers significant increases in CMV antibody titres were frequently seen, probably indicating an activated latent infection. Immunofluorescent antibody assay correlated well with virus isolations and was more sensitive than complement-fixing antibody assay."}
{"id": "PMID:213830", "title": "[Recent developments in the field of infectious diseases].", "content": "A r\u00e9sum\u00e9 is presented of recent developments in the field of infectious diseases of particular interest of practising physicians. Examples are given to illustrate recent discoveries concerning the frequent misuse of antibiotics, the problem of infections developing in hospitalized patients, the biology of microbial infection, the etiology of well-known illnesses, new infectious diseases, and the development of vaccines. It is evident that the rate at which new and important information is evident that the rate at which new and important information is being reported demands particular effort in medical school teaching to ensure that students learn how to acquire and evaluate new information as well as how to discard ideas which are no longer valid.", "contents": "[Recent developments in the field of infectious diseases]. A r\u00e9sum\u00e9 is presented of recent developments in the field of infectious diseases of particular interest of practising physicians. Examples are given to illustrate recent discoveries concerning the frequent misuse of antibiotics, the problem of infections developing in hospitalized patients, the biology of microbial infection, the etiology of well-known illnesses, new infectious diseases, and the development of vaccines. It is evident that the rate at which new and important information is evident that the rate at which new and important information is being reported demands particular effort in medical school teaching to ensure that students learn how to acquire and evaluate new information as well as how to discard ideas which are no longer valid."}
{"id": "PMID:213831", "title": "[Low HDL cholesterol in close relatives and patients with myocardial infarct].", "content": "Male patients aged 40 to 59 who had had acute myocardial infarction three months previously displayed a lower HDL cholesterol than the HDL cholesterol of an apparently healthy control group. The male first degree relatives of patients with acute myocardial infarction, like the patients with coronary disease, had a low HDL cholesterol which differed significantly from the HDL cholesterol of the control group. Low HDL cholesterol appears to be a better \"marker\" of patients with coronary disease and relatives of patients with acute myocardial infarction than serum cholesterol and triglycerides. The importance of low HDL' cholesterol could be related to the role of HDL in the cholesterol transport system from the peripheral tissues.", "contents": "[Low HDL cholesterol in close relatives and patients with myocardial infarct]. Male patients aged 40 to 59 who had had acute myocardial infarction three months previously displayed a lower HDL cholesterol than the HDL cholesterol of an apparently healthy control group. The male first degree relatives of patients with acute myocardial infarction, like the patients with coronary disease, had a low HDL cholesterol which differed significantly from the HDL cholesterol of the control group. Low HDL cholesterol appears to be a better \"marker\" of patients with coronary disease and relatives of patients with acute myocardial infarction than serum cholesterol and triglycerides. The importance of low HDL' cholesterol could be related to the role of HDL in the cholesterol transport system from the peripheral tissues."}
{"id": "PMID:213832", "title": "Cellular interactions uncouple beta-adrenergic receptors from adenylate cyclase.", "content": "C6 glioma cells and B104 neuroblastoma cells both possess adenylate cyclase activity, but only C6 cells have beta-adrenergic receptors. However, when cocultured with B104 cells, C6 cells show a marked decrease in their ability to accumulate adenosine 3', 5'-monophosphate upon stimulation with beta receptor agonists. Since both beta receptors and cholera toxin-stimulated adenylate cyclase activities are present in C6/B104 cocultures, we conclude that the beta receptor/adenylate cyclase transduction mechanism in cocultured C6 cells is uncoupled.", "contents": "Cellular interactions uncouple beta-adrenergic receptors from adenylate cyclase. C6 glioma cells and B104 neuroblastoma cells both possess adenylate cyclase activity, but only C6 cells have beta-adrenergic receptors. However, when cocultured with B104 cells, C6 cells show a marked decrease in their ability to accumulate adenosine 3', 5'-monophosphate upon stimulation with beta receptor agonists. Since both beta receptors and cholera toxin-stimulated adenylate cyclase activities are present in C6/B104 cocultures, we conclude that the beta receptor/adenylate cyclase transduction mechanism in cocultured C6 cells is uncoupled."}
{"id": "PMID:213833", "title": "Feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants: alpha-receptor mediation.", "content": "The use of different receptor blocking agents and single-unit recording techniques indicates that feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants is mediated by presynaptic alpha-receptors. After chronic imipramine treatment, noradrenaline neurons in the locus coeruleus of rat brain remained partly depressed, in agreement with clinical data. They were, however, resistant to further inhibition by imipramine or clonidine.", "contents": "Feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants: alpha-receptor mediation. The use of different receptor blocking agents and single-unit recording techniques indicates that feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants is mediated by presynaptic alpha-receptors. After chronic imipramine treatment, noradrenaline neurons in the locus coeruleus of rat brain remained partly depressed, in agreement with clinical data. They were, however, resistant to further inhibition by imipramine or clonidine."}
{"id": "PMID:213834", "title": "[Etiology of hemoptyses].", "content": "From hemoptyses as main symptom for the admission of patients during 1975 and 1976 in the pulmonary disease department of a parisian hospital, a retrospective study of the causes of hemoptyses is made by the authors. In 18% of the cases, hemoptysis was the unique revealing symptom of the disease. Tuberculosis and cancer are the main causes, but, now, their rate is inverted : 30% for cancer, 21% for tuberculosis, but in addition there are 9% in relation with sequelae of tuberculosis. Among the other causes, bronchiectases keep an important place, just as cardiovasculary diseases. But there is a portion of patients for whom the cause of the hemoptysis cannot be found. As bronchologic and vasculary explorations are developed, this portion of patients will diminish but will not disappear, because mechanisms of hemoptysis will be better explained but not the real cause.", "contents": "[Etiology of hemoptyses]. From hemoptyses as main symptom for the admission of patients during 1975 and 1976 in the pulmonary disease department of a parisian hospital, a retrospective study of the causes of hemoptyses is made by the authors. In 18% of the cases, hemoptysis was the unique revealing symptom of the disease. Tuberculosis and cancer are the main causes, but, now, their rate is inverted : 30% for cancer, 21% for tuberculosis, but in addition there are 9% in relation with sequelae of tuberculosis. Among the other causes, bronchiectases keep an important place, just as cardiovasculary diseases. But there is a portion of patients for whom the cause of the hemoptysis cannot be found. As bronchologic and vasculary explorations are developed, this portion of patients will diminish but will not disappear, because mechanisms of hemoptysis will be better explained but not the real cause."}
{"id": "PMID:213835", "title": "[Acute hyperparathyroidism, diagnosis and treatment. 10 recent cases].", "content": "The authors report 10 observations of acute hyperparathyro\u00efdism crisis cases operated without death. They draw their conclusions from their own experience and from published cases. The evolution on the medical treatment is invariably mortal. The logical treatment is surgery. The operation is a true emergency, preceded by a brief but intensive medical treatment which checks dehydratation up and bring the blood calcium level down.", "contents": "[Acute hyperparathyroidism, diagnosis and treatment. 10 recent cases]. The authors report 10 observations of acute hyperparathyro\u00efdism crisis cases operated without death. They draw their conclusions from their own experience and from published cases. The evolution on the medical treatment is invariably mortal. The logical treatment is surgery. The operation is a true emergency, preceded by a brief but intensive medical treatment which checks dehydratation up and bring the blood calcium level down."}
{"id": "PMID:213836", "title": "[Spinal cord compression caused by malignant non-Hodgkin lymphomas. 13 cases].", "content": "The authors report 13 cases which permitted them to discuss the clinical signs, which were multiple, completed by further investigations of which the most important was lipiodol myelography. The treatment included usually surgical operation accompanied by radiotherapy, chemotherapy and sometimes immunotherapy. This combined treatment gave a better prognosis espeically in patients operated at stages I, II and III, and we obtained 25% favourable results.", "contents": "[Spinal cord compression caused by malignant non-Hodgkin lymphomas. 13 cases]. The authors report 13 cases which permitted them to discuss the clinical signs, which were multiple, completed by further investigations of which the most important was lipiodol myelography. The treatment included usually surgical operation accompanied by radiotherapy, chemotherapy and sometimes immunotherapy. This combined treatment gave a better prognosis espeically in patients operated at stages I, II and III, and we obtained 25% favourable results."}
{"id": "PMID:213837", "title": "[The treatment of migraine and tension headaches with amitriptyline (author's transl)].", "content": "Study of 100 patients followed up for over one year, including 26 cases of migraine (4 classical migraine) and 74 cases of tension headache associated or not with muscular tension. With dihydroergotamin alone 16 cases of migraine, and with amitriptyline alone 17 cases experienced excellent to fair relief, while with the association of both drugs, 21 excellent results were obtained. Among tension headaches patients, 53 were relieved with amitriptyline alone, 56 when DHE was added. The activity of amitriptyline in lower dosages is very likely not an anti-depressant one, but connected with catecholamines metabolism. Dosage must be adjusted in each individual case. The efficiency of DHE in tension headaches suggest a possible part of vaso-motor mechanisms in such cases.", "contents": "[The treatment of migraine and tension headaches with amitriptyline (author's transl)]. Study of 100 patients followed up for over one year, including 26 cases of migraine (4 classical migraine) and 74 cases of tension headache associated or not with muscular tension. With dihydroergotamin alone 16 cases of migraine, and with amitriptyline alone 17 cases experienced excellent to fair relief, while with the association of both drugs, 21 excellent results were obtained. Among tension headaches patients, 53 were relieved with amitriptyline alone, 56 when DHE was added. The activity of amitriptyline in lower dosages is very likely not an anti-depressant one, but connected with catecholamines metabolism. Dosage must be adjusted in each individual case. The efficiency of DHE in tension headaches suggest a possible part of vaso-motor mechanisms in such cases."}
{"id": "PMID:213838", "title": "[System e in acute hepatitis B].", "content": "HBeAg and Ab are investigated by simple radial immunodiffusion in dextrane following Magnius. 14 patients (28%) were HBeAg positive and 2 patients HBeAb positive (4%). HBsAg subtyping was ad in 6 cases and ay in further 5. No relation was found between both determinants and HBeAg. Six of the 10 patients with HBeAg in their sera developed chronic liver disease o fulminant hepatitis, while only 3 of the 21 HBeAg negative controls did so (p less than 0.05). HBeAg is a marker of the evolution of virus B hepatitis.", "contents": "[System e in acute hepatitis B]. HBeAg and Ab are investigated by simple radial immunodiffusion in dextrane following Magnius. 14 patients (28%) were HBeAg positive and 2 patients HBeAb positive (4%). HBsAg subtyping was ad in 6 cases and ay in further 5. No relation was found between both determinants and HBeAg. Six of the 10 patients with HBeAg in their sera developed chronic liver disease o fulminant hepatitis, while only 3 of the 21 HBeAg negative controls did so (p less than 0.05). HBeAg is a marker of the evolution of virus B hepatitis."}
{"id": "PMID:213839", "title": "[Original management in motor, personality and behavior disturbances in ethylic patients in a department of internal medicine (author's transl)].", "content": "33 ethylic patients with motor, personality and behavior disturbances have been treated successfully by tiapride. An oral dose of 5 mg/kg per day was observed to be sufficient in the treatment of lingual and hand tremors. However, in presence of behavior and/or personality disturbances and in predelirium the intramuscular route should be used at the dose of 10 mg/kg per day.", "contents": "[Original management in motor, personality and behavior disturbances in ethylic patients in a department of internal medicine (author's transl)]. 33 ethylic patients with motor, personality and behavior disturbances have been treated successfully by tiapride. An oral dose of 5 mg/kg per day was observed to be sufficient in the treatment of lingual and hand tremors. However, in presence of behavior and/or personality disturbances and in predelirium the intramuscular route should be used at the dose of 10 mg/kg per day."}
{"id": "PMID:213841", "title": "[Use of tiapride in internal medicine (author's transl)].", "content": "Tiapride is tested about 47 in-patients among 6 morbid conditions studied. Tiapride is particulary effective in 4 diseases : delirium tremens, nervous and mental disordes associated with alcoholic addiction are obviously improbed in 2/3 of cases ; the betterment of motor and behaviour disordes concerning old people and the prevention of cephalagia succeding spinal puncture is sure with tiapride. The clinical and biological tolerance is excellent particulary in precarious patients.", "contents": "[Use of tiapride in internal medicine (author's transl)]. Tiapride is tested about 47 in-patients among 6 morbid conditions studied. Tiapride is particulary effective in 4 diseases : delirium tremens, nervous and mental disordes associated with alcoholic addiction are obviously improbed in 2/3 of cases ; the betterment of motor and behaviour disordes concerning old people and the prevention of cephalagia succeding spinal puncture is sure with tiapride. The clinical and biological tolerance is excellent particulary in precarious patients."}
{"id": "PMID:213843", "title": "[Abdominal intercostal hernia. Report of four cases (author's transl)].", "content": "The authors report 4 recent cases of abdominal intercostal hernia and in the light of other cases in the literature, discuss the clinical presentation of this curious and rare disease. Presenting all the characteritics of an uncomplicated hernia, abdominal intercostal hernia is an easy diagnosis on a single clinical examination. Further respiratory and digestive investigations are however essential before undertaking a surgical cure of this hernia at the limit of the thorax and abdomen. Treatment is purely surgical. Instead of the classical treatment by the direct approach, where the risk of relapse is important, one should prefer the transperitoneal approach with use of an inert supple prosthesis. This method gave excellent results with a follow-up of from 1 to 3 years.", "contents": "[Abdominal intercostal hernia. Report of four cases (author's transl)]. The authors report 4 recent cases of abdominal intercostal hernia and in the light of other cases in the literature, discuss the clinical presentation of this curious and rare disease. Presenting all the characteritics of an uncomplicated hernia, abdominal intercostal hernia is an easy diagnosis on a single clinical examination. Further respiratory and digestive investigations are however essential before undertaking a surgical cure of this hernia at the limit of the thorax and abdomen. Treatment is purely surgical. Instead of the classical treatment by the direct approach, where the risk of relapse is important, one should prefer the transperitoneal approach with use of an inert supple prosthesis. This method gave excellent results with a follow-up of from 1 to 3 years."}
{"id": "PMID:213840", "title": "[Functional results of 280 Pean type gastrectomies for chronic Cruveilhier ulcer].", "content": "The authors review 216 gastrectomies of P\u00e9an type for gastric or duodenal ulcer with a follow up of between one and 12 years. In 91 patients, the follow up was more than five years. Six criteria were adopted for the essessment of the functional results: increase in body weight which may be of several types, the diet, post-prandial symptoms, return to work, asthenia recurrent ulcer. Each of these criteria were studied separately in all operated patients and analysed in relation to the follow up period. Except for recurrent ulcer, with occurred in 2% of cases, the results obtained improved with time. A routine study such as Visick's method completes this presentation. The good and very good results were 81% at 5 years, average results were 16% and poor results 3%. The differences between gastric and duodenal ulcer were negligeable. After comparison with the data in the literature, this level study seemed more interesting than a statistical study.", "contents": "[Functional results of 280 Pean type gastrectomies for chronic Cruveilhier ulcer]. The authors review 216 gastrectomies of P\u00e9an type for gastric or duodenal ulcer with a follow up of between one and 12 years. In 91 patients, the follow up was more than five years. Six criteria were adopted for the essessment of the functional results: increase in body weight which may be of several types, the diet, post-prandial symptoms, return to work, asthenia recurrent ulcer. Each of these criteria were studied separately in all operated patients and analysed in relation to the follow up period. Except for recurrent ulcer, with occurred in 2% of cases, the results obtained improved with time. A routine study such as Visick's method completes this presentation. The good and very good results were 81% at 5 years, average results were 16% and poor results 3%. The differences between gastric and duodenal ulcer were negligeable. After comparison with the data in the literature, this level study seemed more interesting than a statistical study."}
{"id": "PMID:213844", "title": "[A new variety of chondrosarcoma : so-called \"chondro-blastic\" sarcomas or \"clear cell\" chondrosarcomas. Pathology and electron microscopy in 5 cases (author's transl)].", "content": "The authors report the pathological and clinical findings in five cases of chondrosarcoma resembling chondroblastic chondrosarcomas as described by Lichtenstein and Bernstein in 1959 and, above all, clear cell chondrosarcomas as described by Unni et al. (1976). These chondrosarcomas have a double peculiarity:--topographic, for their site is often epiphyseal :--anatomica, for they associate, in the usual chondrosarcomatous sectors, areas rich in clear cells, with a rich blood supply, and in some cases a diffuse reactional osteogenesis. Although the long term prognosis is similar to that of all chondrosarcomas, their course is sometimes very slow. One should thus distinguish carefully these tumours from chondroblastomas in spite of certain topographic and radiological similarities.", "contents": "[A new variety of chondrosarcoma : so-called \"chondro-blastic\" sarcomas or \"clear cell\" chondrosarcomas. Pathology and electron microscopy in 5 cases (author's transl)]. The authors report the pathological and clinical findings in five cases of chondrosarcoma resembling chondroblastic chondrosarcomas as described by Lichtenstein and Bernstein in 1959 and, above all, clear cell chondrosarcomas as described by Unni et al. (1976). These chondrosarcomas have a double peculiarity:--topographic, for their site is often epiphyseal :--anatomica, for they associate, in the usual chondrosarcomatous sectors, areas rich in clear cells, with a rich blood supply, and in some cases a diffuse reactional osteogenesis. Although the long term prognosis is similar to that of all chondrosarcomas, their course is sometimes very slow. One should thus distinguish carefully these tumours from chondroblastomas in spite of certain topographic and radiological similarities."}
{"id": "PMID:213845", "title": "[Pleuro-pulmonary complications of typhoid fever. 1case].", "content": "The authors report a case of typhoid fever with pleuro-pulmonary complications and recall their characteristics: Usually early (second week), may appear under treatment, whereas the disease evolves normally. Characterised by the absence of infective phenomena, the multiple manifestations, the fleeting course and the favourable prognosis. This corresponds to the pleuro-pulmonary typhus syndrome described long ago, which is probably due to immunological phenomena. Sometimes late, evolving towards suppuration, abscess formation and empyema with presence of typhoid bacilli, rarely seen nowadays.", "contents": "[Pleuro-pulmonary complications of typhoid fever. 1case]. The authors report a case of typhoid fever with pleuro-pulmonary complications and recall their characteristics: Usually early (second week), may appear under treatment, whereas the disease evolves normally. Characterised by the absence of infective phenomena, the multiple manifestations, the fleeting course and the favourable prognosis. This corresponds to the pleuro-pulmonary typhus syndrome described long ago, which is probably due to immunological phenomena. Sometimes late, evolving towards suppuration, abscess formation and empyema with presence of typhoid bacilli, rarely seen nowadays."}
{"id": "PMID:213849", "title": "Mechanisms of localization of gallium-67 in tumors.", "content": "The mechanism of tumor localization of gallium-67 (67Ga) is not known with certainty, although much information has been derived regarding the biodistribution and subcellular fate of 67Ga in a variety of tumors and other tissues from experimental animals. After intravenous administration, 67Ga is bound to transferrin in the blood, and distributed to liver, lacrimal glands, salivary glands, and soft tissue tumors. Within the cells of the liver and tumors, gallium is found in lysosomes, and rough endoplasmic reticulum. Within these organelles, 67Ga is bound to a variety of macromolecules, including transferrin, ferritin, and a 45,000 molecular weight glycoprotein. Recent studies of tumor cells growing in tissue culture suggest an important role for transferrin in 67Ga tumor uptake. This uptake is mediated by a transferrin specific cellular receptor.", "contents": "Mechanisms of localization of gallium-67 in tumors. The mechanism of tumor localization of gallium-67 (67Ga) is not known with certainty, although much information has been derived regarding the biodistribution and subcellular fate of 67Ga in a variety of tumors and other tissues from experimental animals. After intravenous administration, 67Ga is bound to transferrin in the blood, and distributed to liver, lacrimal glands, salivary glands, and soft tissue tumors. Within the cells of the liver and tumors, gallium is found in lysosomes, and rough endoplasmic reticulum. Within these organelles, 67Ga is bound to a variety of macromolecules, including transferrin, ferritin, and a 45,000 molecular weight glycoprotein. Recent studies of tumor cells growing in tissue culture suggest an important role for transferrin in 67Ga tumor uptake. This uptake is mediated by a transferrin specific cellular receptor."}
{"id": "PMID:213842", "title": "[Extensive cellulitis during chicken-pox. Six causes (author's transl)].", "content": "The authors report 6 cases of extensive cellulitis, in 6 children with chicken-pox. This is a rare complication during this disease. If streptococcal etiology is not always proved, clinical aspect and the dramatic reponse to treatment by penicillin G, characterize this kind of complication.", "contents": "[Extensive cellulitis during chicken-pox. Six causes (author's transl)]. The authors report 6 cases of extensive cellulitis, in 6 children with chicken-pox. This is a rare complication during this disease. If streptococcal etiology is not always proved, clinical aspect and the dramatic reponse to treatment by penicillin G, characterize this kind of complication."}
{"id": "PMID:213850", "title": "Southern Regional Trophoblastic Disease Center, 1972--1977.", "content": "The experience of the Southern Regional Trophoblastic Disease Center includes 222 patients who were referred from January 1972 to October 1977. The initial tissue diagnosis was hydatidiform mole in 212 patients and choriocarcinoma in ten. There was spontaneous remission of 142 (69%) of the moles and one of the choriocarcinomas, and 77 patients developed persistent trophoblastic disease. Of these, 58 had no evidence of metastasis, and all achieved remission with single-drug therapy. Nineteen patients developed metastases; 13 were in the \"good prognosis\" category, and all achieved remission with single-drug therapy. Five (83%) of the six patients with metastases in the \"poor prognosis\" group achieved remission with triple chemotherapy; one died of her disease.", "contents": "Southern Regional Trophoblastic Disease Center, 1972--1977. The experience of the Southern Regional Trophoblastic Disease Center includes 222 patients who were referred from January 1972 to October 1977. The initial tissue diagnosis was hydatidiform mole in 212 patients and choriocarcinoma in ten. There was spontaneous remission of 142 (69%) of the moles and one of the choriocarcinomas, and 77 patients developed persistent trophoblastic disease. Of these, 58 had no evidence of metastasis, and all achieved remission with single-drug therapy. Nineteen patients developed metastases; 13 were in the \"good prognosis\" category, and all achieved remission with single-drug therapy. Five (83%) of the six patients with metastases in the \"poor prognosis\" group achieved remission with triple chemotherapy; one died of her disease."}
{"id": "PMID:213846", "title": "[Steinert's disease and pregnancy].", "content": "The authors present two cases of Steinert's disease associated with successive pregnancies. The interest resides in the possibility of prenatal diagnosis in the light of their characteristic facies, the repeated hydramnios, and the Xray of the uterine contents showing a child with an open mouth. Furthermore, one of the cases was the only in the liteature with that of Sciarra where uterine contractility was recorded during laour.", "contents": "[Steinert's disease and pregnancy]. The authors present two cases of Steinert's disease associated with successive pregnancies. The interest resides in the possibility of prenatal diagnosis in the light of their characteristic facies, the repeated hydramnios, and the Xray of the uterine contents showing a child with an open mouth. Furthermore, one of the cases was the only in the liteature with that of Sciarra where uterine contractility was recorded during laour."}
{"id": "PMID:213851", "title": "Early and subtle signs in low-back sprain.", "content": "The authors have previously reported myalgic hyperalgesia as a useful localizing sign in \"low-back sprain\" patients with no physical findings. This paper describes some other subtle signs related to the phenomenon of denervation supersensitivity which is well known to physiologists and clinicians involved in peripheral nerve disease, yet its related signs have not been applied to low-back pain. Following denervation of some neurons, muscle and peripheral receptors become supersensitive to transmitter substances and to different forms of stimuli. Since the peripheral nerve is a mixed nerve, findings are multiphasic and include autonomic dysfunction, trophic changes, cutaneous and myalgic hyperalgesia, and increased muscle tone. One or more of these signs occurred in 30 patients with secondary low-back pain but less often in 30 patients with primary or mechanical low-back pain; their presence, though slight, in asymptomatic controls may identify those individuals with a vulnerable back.", "contents": "Early and subtle signs in low-back sprain. The authors have previously reported myalgic hyperalgesia as a useful localizing sign in \"low-back sprain\" patients with no physical findings. This paper describes some other subtle signs related to the phenomenon of denervation supersensitivity which is well known to physiologists and clinicians involved in peripheral nerve disease, yet its related signs have not been applied to low-back pain. Following denervation of some neurons, muscle and peripheral receptors become supersensitive to transmitter substances and to different forms of stimuli. Since the peripheral nerve is a mixed nerve, findings are multiphasic and include autonomic dysfunction, trophic changes, cutaneous and myalgic hyperalgesia, and increased muscle tone. One or more of these signs occurred in 30 patients with secondary low-back pain but less often in 30 patients with primary or mechanical low-back pain; their presence, though slight, in asymptomatic controls may identify those individuals with a vulnerable back."}
{"id": "PMID:213847", "title": "[Glucocorticoids and gluco-lipidic metabolism].", "content": "Glucocorticoids increase the stocks of carbohydrate and the supra-hepatic flow of glucose. Their excess produces a centripetal redistribtution of adipose stocks and potentialises adipocyte lipolysis. Although their role of glucose and lipid metabolism is evident, the mechanisms and sites of action of glucocorticoids are multiple and not entirely clear. The actions of glucocorticoids become clear in cases of insulin deficiency, especially when the deficiency is marked, which is of great interest in current medical practice.", "contents": "[Glucocorticoids and gluco-lipidic metabolism]. Glucocorticoids increase the stocks of carbohydrate and the supra-hepatic flow of glucose. Their excess produces a centripetal redistribtution of adipose stocks and potentialises adipocyte lipolysis. Although their role of glucose and lipid metabolism is evident, the mechanisms and sites of action of glucocorticoids are multiple and not entirely clear. The actions of glucocorticoids become clear in cases of insulin deficiency, especially when the deficiency is marked, which is of great interest in current medical practice."}
{"id": "PMID:213852", "title": "Preoperative and follow-up bone scans in patients with primary carcinoma of the breast.", "content": "We have attempted to evaluate the role of preoperative and postoperative bone scans in patients with localized carcinoma of the breast. The yield of positive preoperative scans in patients with Stages I and II disease is low and confounded by a relatively high percentage of false-positive results. Conversely, 16 per cent of patients with Stage III disease had evidence of bony metastasis at the time of operation. Positive bone scans were found three times as frequently in patients with axillary node involvement than in those without. Thirty per cent of those observed for varying times up to 41 months had evidence of bony metastases. Again, there was a correlation with initial clinical staging with 3.6 to 8.0 times more conversions in patients with Stage II or III disease than in those with Stage I disease. It appears that the majority of metastases to the bone become apparent within the first years. This observation deserves further study to elaborate the natural history of metastatic carcinoma of the breast.", "contents": "Preoperative and follow-up bone scans in patients with primary carcinoma of the breast. We have attempted to evaluate the role of preoperative and postoperative bone scans in patients with localized carcinoma of the breast. The yield of positive preoperative scans in patients with Stages I and II disease is low and confounded by a relatively high percentage of false-positive results. Conversely, 16 per cent of patients with Stage III disease had evidence of bony metastasis at the time of operation. Positive bone scans were found three times as frequently in patients with axillary node involvement than in those without. Thirty per cent of those observed for varying times up to 41 months had evidence of bony metastases. Again, there was a correlation with initial clinical staging with 3.6 to 8.0 times more conversions in patients with Stage II or III disease than in those with Stage I disease. It appears that the majority of metastases to the bone become apparent within the first years. This observation deserves further study to elaborate the natural history of metastatic carcinoma of the breast."}
{"id": "PMID:213848", "title": "[Evaluation of thyroid function in children (author's transl)].", "content": "Two main methods must be used in every case for evaluation of thyroid function in children : measurement of plasma thyroxin T4 and thyroid scanning with technetium. If accurately done, they may be sufficient for practical purposes. However, the wide number and variety of methods available for thyroid evaluation offers to pediatricians a choice sometimes difficult. The aim of this review is to summarize the meaning and accuracy of current methods and their usefulness in diagnosis and study of thyroid diseases of pediatric patients.", "contents": "[Evaluation of thyroid function in children (author's transl)]. Two main methods must be used in every case for evaluation of thyroid function in children : measurement of plasma thyroxin T4 and thyroid scanning with technetium. If accurately done, they may be sufficient for practical purposes. However, the wide number and variety of methods available for thyroid evaluation offers to pediatricians a choice sometimes difficult. The aim of this review is to summarize the meaning and accuracy of current methods and their usefulness in diagnosis and study of thyroid diseases of pediatric patients."}
{"id": "PMID:213853", "title": "Results of surgical treatment of carcinoma of the lung by stage and cell type.", "content": "The results of surgical treatment in 470 patients with carcinoma of the lung were analyzed by stage of disease and by histologic cell type. The need for accurate staging in selecting treatment and in prognosis for survival is emphasized. Surgical resection improved survival time in all categories of patients by effective local control of the lesion. The over-all five year survival rate was 14 per cent. Early stages of carcinoma of the lung were more amenable to surgical cure. The highest five year survival rate was 43 per cent and was observed in resected Stage I carcinomas. Only 29 per cent of this group died of the disease and 28 per cent, of other causes. The continued high incidence of death due to distant metastases underlines the necessity of combining operation with other forms of treatment.", "contents": "Results of surgical treatment of carcinoma of the lung by stage and cell type. The results of surgical treatment in 470 patients with carcinoma of the lung were analyzed by stage of disease and by histologic cell type. The need for accurate staging in selecting treatment and in prognosis for survival is emphasized. Surgical resection improved survival time in all categories of patients by effective local control of the lesion. The over-all five year survival rate was 14 per cent. Early stages of carcinoma of the lung were more amenable to surgical cure. The highest five year survival rate was 43 per cent and was observed in resected Stage I carcinomas. Only 29 per cent of this group died of the disease and 28 per cent, of other causes. The continued high incidence of death due to distant metastases underlines the necessity of combining operation with other forms of treatment."}
{"id": "PMID:213854", "title": "Effects of intravenous nutrition on tumor growth and host immunocompetence in malnourished animals.", "content": "To evaluate the effects of oral and intravenous nutritional repletion on tumor growth and host immunocompetence in malnourished animals, 60 adult purified protein derivative (PPD) positive Buffalo rats were inoculated with Morris hepatoma 5123 and were fed a regular diet for 14 days. All animals then were switched to a high carbohydrate, protein-free diet for the next 14 days, at which time only 30% of the animals remained PPD positive. Rats then were divided into three groups: group I underwent superior vena cava catheterization and received a constant infusion of 25% dextrose--4.25% amino acid solution; group II was switched to the regular protein diet orally ad libitum; and group III remained on the oral protein-free diet. PPD reactivities were measured prior to death 7 days later. Group I animals gained an average of 14 gm of body weight, and 91% of the animals were PPD positive. Group II animals lost an average of 17 gm of body weight, but 78% of the animals were PPD positive. Group III animals lost an average of 23 gm of body weight, and only 12% of the animals remained PPD positive. Absolute tumor weight and tumor weight: body weight ratios were not significantly different among the three groups of animals. Provision of adequate nutrition intravenously to malnourished tumor-bearing animals restores body weight and host immunocompetence without adversely stimulating tumor growth out of proportion to growth of the host.", "contents": "Effects of intravenous nutrition on tumor growth and host immunocompetence in malnourished animals. To evaluate the effects of oral and intravenous nutritional repletion on tumor growth and host immunocompetence in malnourished animals, 60 adult purified protein derivative (PPD) positive Buffalo rats were inoculated with Morris hepatoma 5123 and were fed a regular diet for 14 days. All animals then were switched to a high carbohydrate, protein-free diet for the next 14 days, at which time only 30% of the animals remained PPD positive. Rats then were divided into three groups: group I underwent superior vena cava catheterization and received a constant infusion of 25% dextrose--4.25% amino acid solution; group II was switched to the regular protein diet orally ad libitum; and group III remained on the oral protein-free diet. PPD reactivities were measured prior to death 7 days later. Group I animals gained an average of 14 gm of body weight, and 91% of the animals were PPD positive. Group II animals lost an average of 17 gm of body weight, but 78% of the animals were PPD positive. Group III animals lost an average of 23 gm of body weight, and only 12% of the animals remained PPD positive. Absolute tumor weight and tumor weight: body weight ratios were not significantly different among the three groups of animals. Provision of adequate nutrition intravenously to malnourished tumor-bearing animals restores body weight and host immunocompetence without adversely stimulating tumor growth out of proportion to growth of the host."}
{"id": "PMID:213856", "title": "[Benign tumors of the lung and pleura (author's transl)].", "content": "218 benign tumors of the lung and pleura, 190 of which were operated, are discussed. Little doubt exists about the necessity of operative removal in cases of benign pleuro-pulmonary tumors. Therapeutic management depends on histology, localisation and the extent of growth. The majority of untreated benign tumors have a poor prognosis even if malignant degeneration does not occur. Postoperative prognosis of rehabilitation and resocialization is good.", "contents": "[Benign tumors of the lung and pleura (author's transl)]. 218 benign tumors of the lung and pleura, 190 of which were operated, are discussed. Little doubt exists about the necessity of operative removal in cases of benign pleuro-pulmonary tumors. Therapeutic management depends on histology, localisation and the extent of growth. The majority of untreated benign tumors have a poor prognosis even if malignant degeneration does not occur. Postoperative prognosis of rehabilitation and resocialization is good."}
{"id": "PMID:213857", "title": "Use of live varicella vaccine in children with acute leukemia.", "content": "Seven children with acute leukemia were given a live attenuated varicella vaccine and successfully seroconverted with minimal clinical reactions. One of them was vaccinated immediately after the contact with natural varicella and successfully prevented from natural infection.", "contents": "Use of live varicella vaccine in children with acute leukemia. Seven children with acute leukemia were given a live attenuated varicella vaccine and successfully seroconverted with minimal clinical reactions. One of them was vaccinated immediately after the contact with natural varicella and successfully prevented from natural infection."}
{"id": "PMID:213863", "title": "Separation of rat-liver phosphoprotein phosphatases active on phosphorylated pyruvate kinase (type L).", "content": "The substrate specificity of rat liver phosphoprotein phosphatases has been investigated. The enzymes were resolved into three fractions, termed A, B and C, on elution from DEAE-cellulose with apparent molecular weights, as determined by Sephadex G-200 chromatography, of approximately 250 000, 250 000 and 140 000, respectively. All fractions catalyzed the dephosphorylation of calf-thymus phosphohistones, salmon phosphoprotamine and rabbit skeletal muscle phosphorylase a. The major portion of the activity towards these substrates was found in fraction B. The activity towards rat liver phosphopyruvate kinase (type L) resided almost exclusively in fractions B and C. It is concluded that rat liver contains multiple forms of phosphoprotein phosphatases and that phosphatases of fraction B and C are the major activities towards phosphopyruvate kinase.", "contents": "Separation of rat-liver phosphoprotein phosphatases active on phosphorylated pyruvate kinase (type L). The substrate specificity of rat liver phosphoprotein phosphatases has been investigated. The enzymes were resolved into three fractions, termed A, B and C, on elution from DEAE-cellulose with apparent molecular weights, as determined by Sephadex G-200 chromatography, of approximately 250 000, 250 000 and 140 000, respectively. All fractions catalyzed the dephosphorylation of calf-thymus phosphohistones, salmon phosphoprotamine and rabbit skeletal muscle phosphorylase a. The major portion of the activity towards these substrates was found in fraction B. The activity towards rat liver phosphopyruvate kinase (type L) resided almost exclusively in fractions B and C. It is concluded that rat liver contains multiple forms of phosphoprotein phosphatases and that phosphatases of fraction B and C are the major activities towards phosphopyruvate kinase."}
{"id": "PMID:213864", "title": "Interstitial cystitis: early diagnosis, pathology, and treatment.", "content": "In a retrospective review, 52 patients with interstitial cystitis have been studied. Patients with persistent lower tract irritative symptoms, repeatedly sterile urine, and negative urine cytology must be suspected of having interstitial cystitis, and a diagnosis of urethral syndrome in such patients is highly questionable until cystoscopy under anesthesia has been performed. We believe that the finding of multiple petechia-like hemorrhages (glomerulations) on the second distention of the bladder is the hallmark of interstitial cystitis, and that a reduced bladder capacity and a Hunner's ulcer represent a different (classic) stage of this disease. In all stages, the characteristic histologic finidng is submucosal edema and vasodilation. The presence of eosinophils and mast cells is variable, and even in the classic disease the muscularis often appears to be normal. Immuno fluorescent studies and laboratory tests, including the fluorescent antinuclear antibody test (FANA), have not helped us to diagnose (or investigate) interstitial cystitis. Bladder instillations with a 0.4 per cent solution of oxychlorosene sodium (Clorpactin WCS-90) have provided remarkable relief for many patients with this disease, particulary those with the classic form.", "contents": "Interstitial cystitis: early diagnosis, pathology, and treatment. In a retrospective review, 52 patients with interstitial cystitis have been studied. Patients with persistent lower tract irritative symptoms, repeatedly sterile urine, and negative urine cytology must be suspected of having interstitial cystitis, and a diagnosis of urethral syndrome in such patients is highly questionable until cystoscopy under anesthesia has been performed. We believe that the finding of multiple petechia-like hemorrhages (glomerulations) on the second distention of the bladder is the hallmark of interstitial cystitis, and that a reduced bladder capacity and a Hunner's ulcer represent a different (classic) stage of this disease. In all stages, the characteristic histologic finidng is submucosal edema and vasodilation. The presence of eosinophils and mast cells is variable, and even in the classic disease the muscularis often appears to be normal. Immuno fluorescent studies and laboratory tests, including the fluorescent antinuclear antibody test (FANA), have not helped us to diagnose (or investigate) interstitial cystitis. Bladder instillations with a 0.4 per cent solution of oxychlorosene sodium (Clorpactin WCS-90) have provided remarkable relief for many patients with this disease, particulary those with the classic form."}
{"id": "PMID:213865", "title": "Accuracy of preoperative studies in staging nonseminomatous germ cell testicular tumors.", "content": "The preoperative staging procedures used in 45 patients with surgical Stage I and Stage II nonseminomatous germ cell tumors of the testis were analyzed retrospectively. Our results indicate that gallium-67-citrate scan and supraclavicular lymph node biopsy add little information in the routine preoperative evaluation of these patients. Bipedal lymphangiography, in our experience, was no more accurate than excretory urograms in selecting patients with retroperitoneal disease and in addition provides no information regarding the status of the upper urinary tract. Thus, we suggest that physical examination, excretory urography, chest x-ray film, whole lung tomography, serum tumor markers, and liver scan provide sufficient information to proceed with surgical treatment when appropriate.", "contents": "Accuracy of preoperative studies in staging nonseminomatous germ cell testicular tumors. The preoperative staging procedures used in 45 patients with surgical Stage I and Stage II nonseminomatous germ cell tumors of the testis were analyzed retrospectively. Our results indicate that gallium-67-citrate scan and supraclavicular lymph node biopsy add little information in the routine preoperative evaluation of these patients. Bipedal lymphangiography, in our experience, was no more accurate than excretory urograms in selecting patients with retroperitoneal disease and in addition provides no information regarding the status of the upper urinary tract. Thus, we suggest that physical examination, excretory urography, chest x-ray film, whole lung tomography, serum tumor markers, and liver scan provide sufficient information to proceed with surgical treatment when appropriate."}
{"id": "PMID:213866", "title": "Signet ring cell carcinoma of bladder.", "content": "The ninth reported case of primary signet ring cell carcinoma of the bladder is described. This particular tumor, whose histology was examined repeatedly during its evolution, showed an interesting change in microscopic appearance after irradiation. The emerging features of signet ring cell carcinoma of the bladder are discussed.", "contents": "Signet ring cell carcinoma of bladder. The ninth reported case of primary signet ring cell carcinoma of the bladder is described. This particular tumor, whose histology was examined repeatedly during its evolution, showed an interesting change in microscopic appearance after irradiation. The emerging features of signet ring cell carcinoma of the bladder are discussed."}
{"id": "PMID:213868", "title": "High density lipoproteins--correlation with cardiovascular disease in hemodialysis patients.", "content": "1) HDL levels are low in hemodialysis patients. 2) Lipid abnormalities do not correlate with the presence of CVD in hemodialysis patients. 3) Smoking may not effect blood lipid levels in hemodialysis patients. 4) Nandrolone decanoate may not play a role in CVD in hemodialysis patients. 5) Longer time on hemodialysis does not result in a decrease in triglyceride or increase in HDL levels.", "contents": "High density lipoproteins--correlation with cardiovascular disease in hemodialysis patients. 1) HDL levels are low in hemodialysis patients. 2) Lipid abnormalities do not correlate with the presence of CVD in hemodialysis patients. 3) Smoking may not effect blood lipid levels in hemodialysis patients. 4) Nandrolone decanoate may not play a role in CVD in hemodialysis patients. 5) Longer time on hemodialysis does not result in a decrease in triglyceride or increase in HDL levels."}
{"id": "PMID:213872", "title": "Susceptibility of chicks to infectious bursal disease (IBD) following vaccination of their parents with live IBD vaccine.", "content": "Vaccination of parent chickens with a commercial live infectious bursal disease (IBD) vaccine under field conditions at varying ages and by different routes resulted in variable susceptibility to the disease in their chicks. There was little correlation between the methods of vaccination and the levels of immunity in the chicks. There was some evidence that levels of transferred immunity decreased with the age of the parents. Of five flocks examined, the onset of susceptibility to IBD occurred at two days of age in two flocks and about one week of age in the other three. Four flocks were completely susceptible by the 27th day, the other at 31 days. Precipitins were demonstrated at day old in 100 per cent of chicks in three flocks and in 80 per cent in the other two. The precipitins had disappeared in all flocks by 17 days of age.", "contents": "Susceptibility of chicks to infectious bursal disease (IBD) following vaccination of their parents with live IBD vaccine. Vaccination of parent chickens with a commercial live infectious bursal disease (IBD) vaccine under field conditions at varying ages and by different routes resulted in variable susceptibility to the disease in their chicks. There was little correlation between the methods of vaccination and the levels of immunity in the chicks. There was some evidence that levels of transferred immunity decreased with the age of the parents. Of five flocks examined, the onset of susceptibility to IBD occurred at two days of age in two flocks and about one week of age in the other three. Four flocks were completely susceptible by the 27th day, the other at 31 days. Precipitins were demonstrated at day old in 100 per cent of chicks in three flocks and in 80 per cent in the other two. The precipitins had disappeared in all flocks by 17 days of age."}
{"id": "PMID:213874", "title": "[Granular cell tumor and the phagocytozing form of Schwann cells. Electron microscopic examinations of 3 cases (author's transl)].", "content": "In granular cell tumors, the granule-containing tumor cells and their processes form rounded complexes surrounded by a common bounding membrane. In the tumor, these complexes are closely related to the peripheral nerves and are seen in the perineurium and in the endoneurium. In addition, there are mixed complexes composed both of Schwann cells and granular tumor cells: the two types of cells are in close contact with each other and are also surrounded by a common bounding membrane. Furthermore, there one contacts between granular tumor cells and axons. These observations strongly suggest the existence of a relationship between Schwann cells and the cells of granular cell tumors. A comparison between the granular tumor cells and the phagocytic forms of Schwann cells reveals striking similarities: the granular cell tumor complexes are comparable with the B\u00fcngner bands of phagocytozing Schwann cells. A relationship between granular cell tumors and the phagocytozing form of Schwann cells is therefore assumed.", "contents": "[Granular cell tumor and the phagocytozing form of Schwann cells. Electron microscopic examinations of 3 cases (author's transl)]. In granular cell tumors, the granule-containing tumor cells and their processes form rounded complexes surrounded by a common bounding membrane. In the tumor, these complexes are closely related to the peripheral nerves and are seen in the perineurium and in the endoneurium. In addition, there are mixed complexes composed both of Schwann cells and granular tumor cells: the two types of cells are in close contact with each other and are also surrounded by a common bounding membrane. Furthermore, there one contacts between granular tumor cells and axons. These observations strongly suggest the existence of a relationship between Schwann cells and the cells of granular cell tumors. A comparison between the granular tumor cells and the phagocytic forms of Schwann cells reveals striking similarities: the granular cell tumor complexes are comparable with the B\u00fcngner bands of phagocytozing Schwann cells. A relationship between granular cell tumors and the phagocytozing form of Schwann cells is therefore assumed."}
{"id": "PMID:213895", "title": "[Glucuronic acid, glucuronyltransferase and estrogens in breast cancer and precancer].", "content": "The glucuronic acid level in the serum and urine, the diural excretion of estrogens and 17-KS with the urine, the activity of glucuronyltransferase are reported in 101 patients with benign and malignant tumors and in 22 healthy females. The decrease in the activity of glucurolytransferase and increase in the percentage of free (nonconjugated) estrogens in patients with malignant tumors of the mammary gland are noted, the analogous results were obtained in patients with benign tumors, but these are statistically insignificant. The decrease of the glucuronyltransferase activity is suggested to result in the development of relative hyperestrogen in normal total excretion.", "contents": "[Glucuronic acid, glucuronyltransferase and estrogens in breast cancer and precancer]. The glucuronic acid level in the serum and urine, the diural excretion of estrogens and 17-KS with the urine, the activity of glucuronyltransferase are reported in 101 patients with benign and malignant tumors and in 22 healthy females. The decrease in the activity of glucurolytransferase and increase in the percentage of free (nonconjugated) estrogens in patients with malignant tumors of the mammary gland are noted, the analogous results were obtained in patients with benign tumors, but these are statistically insignificant. The decrease of the glucuronyltransferase activity is suggested to result in the development of relative hyperestrogen in normal total excretion."}
{"id": "PMID:213896", "title": "[Differentiated expression of the viral genome in mammalian cells transformed by the Rous sarcoma virus].", "content": "In hybridization of 3H-DNA-product of Rous sarcoma virus with the RNA isolated from mammalian cells transformed by the virus concerned, it was found, that the virus-specific RNA, isolated from cryptovirogenic cells RVP-3, differs in nucleotide sequences from virogenic cells XC, XPO and TWERC.", "contents": "[Differentiated expression of the viral genome in mammalian cells transformed by the Rous sarcoma virus]. In hybridization of 3H-DNA-product of Rous sarcoma virus with the RNA isolated from mammalian cells transformed by the virus concerned, it was found, that the virus-specific RNA, isolated from cryptovirogenic cells RVP-3, differs in nucleotide sequences from virogenic cells XC, XPO and TWERC."}
{"id": "PMID:213903", "title": "[Degradation of C1q, the first subcomponent of the complement sequence, by synovial collagenase from patients with rheumatoid arthritis (author's transl)].", "content": "Human C1q is shown to be degraded by high concentrations of RA synovial collagenase (enzyme : substrate ratio 2 : 1). The collagen-like sequence of C1q is attacked by the enzyme. A possible cleavage site is described and compared with the cleavage site in collagen.", "contents": "[Degradation of C1q, the first subcomponent of the complement sequence, by synovial collagenase from patients with rheumatoid arthritis (author's transl)]. Human C1q is shown to be degraded by high concentrations of RA synovial collagenase (enzyme : substrate ratio 2 : 1). The collagen-like sequence of C1q is attacked by the enzyme. A possible cleavage site is described and compared with the cleavage site in collagen."}
{"id": "PMID:213904", "title": "[Detection of collagenase in passive haemagglutination using collagen-coated erythrocytes (author's transl)].", "content": "Human rheumatoid arthritis (RA) collagenase and bacterial collagenase were shown to agglutinate collagen-coated erythrocytes. Native collagens of type I and type II reacted equally well, while denatured collagens showed less distinct agglutination activity. The sensitivity of the method for the detection of purified bacterial collagenase from Clostridium histolyticum is very high (100 pg). It is, however, low for human RA collagenase. The agglutination reaction is not inhibited by concentrations of native collagen causing distinct inhibition of anticollagen sera (2mg%). EDTA inhibits the agglutination completely.", "contents": "[Detection of collagenase in passive haemagglutination using collagen-coated erythrocytes (author's transl)]. Human rheumatoid arthritis (RA) collagenase and bacterial collagenase were shown to agglutinate collagen-coated erythrocytes. Native collagens of type I and type II reacted equally well, while denatured collagens showed less distinct agglutination activity. The sensitivity of the method for the detection of purified bacterial collagenase from Clostridium histolyticum is very high (100 pg). It is, however, low for human RA collagenase. The agglutination reaction is not inhibited by concentrations of native collagen causing distinct inhibition of anticollagen sera (2mg%). EDTA inhibits the agglutination completely."}
{"id": "PMID:213906", "title": "[Primary lymphosarcoma of the lung (author's transl)].", "content": "The histological, histochemical and cytological changes were reported in 6 patients with primary lymphosarcoma of the lung. All cases are diffuse lymphocytic lymphosarcomas, histochemically with a similar enzymatic behaviour. Cytologically, small lymphocytes with different degrees of anaplasia were observed.", "contents": "[Primary lymphosarcoma of the lung (author's transl)]. The histological, histochemical and cytological changes were reported in 6 patients with primary lymphosarcoma of the lung. All cases are diffuse lymphocytic lymphosarcomas, histochemically with a similar enzymatic behaviour. Cytologically, small lymphocytes with different degrees of anaplasia were observed."}
{"id": "PMID:213907", "title": "[Development of the ossification centres of the skeleton of the hand in patients with idiopathic scoliosis (author's transl)].", "content": "In 84 patients with idiopathic scoliosis, the skeletal age was estimated by the method of Greulich and Pyle. The average values were within the normal distribution curve. According to Prader, the normal values for skeletal age lie within + or -20% of the chronological age. Using his criteria, all our values are within the normal range.", "contents": "[Development of the ossification centres of the skeleton of the hand in patients with idiopathic scoliosis (author's transl)]. In 84 patients with idiopathic scoliosis, the skeletal age was estimated by the method of Greulich and Pyle. The average values were within the normal distribution curve. According to Prader, the normal values for skeletal age lie within + or -20% of the chronological age. Using his criteria, all our values are within the normal range."}
{"id": "PMID:213910", "title": "[About the importance of chemical flocculation of wastewater in regard to hygienical aspects (microbiological and virological examinations in a wastewater treatment plant) (author's transl)].", "content": "In a small wastewater treatment plant corresponding samples from the intake and outtake of the chemical flocculation were chemically, microbiologically and virologically investigated and compared. It was found that both, the plate count and the number of coliforms, decreased about 90% to 95%. The phosphate content went down about 88%. The BOD5 reduction was ca. 80%, the COD reduction ca. 50%. Poliomyelitisviruses were found regularly in the intake but never in the outtake. Specially in regard to the high plate count- and virusreduction the chemical flocculation seems to be remarkable from the hygienical point of view not only for limnic but also for coastal waters.", "contents": "[About the importance of chemical flocculation of wastewater in regard to hygienical aspects (microbiological and virological examinations in a wastewater treatment plant) (author's transl)]. In a small wastewater treatment plant corresponding samples from the intake and outtake of the chemical flocculation were chemically, microbiologically and virologically investigated and compared. It was found that both, the plate count and the number of coliforms, decreased about 90% to 95%. The phosphate content went down about 88%. The BOD5 reduction was ca. 80%, the COD reduction ca. 50%. Poliomyelitisviruses were found regularly in the intake but never in the outtake. Specially in regard to the high plate count- and virusreduction the chemical flocculation seems to be remarkable from the hygienical point of view not only for limnic but also for coastal waters."}
{"id": "PMID:213908", "title": "[Motor conditioned reactions at different stages of normal human nocturnal sleep and their electrographic correlates].", "content": "Motor conditioned reaction was studied at different sleep phases in 13 subjects by EMG and mechanogram parameters compared to SGR and EEG. During paradoxical phase motor conditioned reaction appeared more often than in the slow-wave sleep, but in a reduced form. At various sleep stages the motor conditioned reaction regularly appeared at the background of the rise in the level of cortical functional state before conditioned stimulus. At all sleep stages completed motor reaction is fixed in the consciousness. However, amnesia of conditional stimulus perception and of motor reaction to it is rapidly developed, in particular in the slow-wave phase.", "contents": "[Motor conditioned reactions at different stages of normal human nocturnal sleep and their electrographic correlates]. Motor conditioned reaction was studied at different sleep phases in 13 subjects by EMG and mechanogram parameters compared to SGR and EEG. During paradoxical phase motor conditioned reaction appeared more often than in the slow-wave sleep, but in a reduced form. At various sleep stages the motor conditioned reaction regularly appeared at the background of the rise in the level of cortical functional state before conditioned stimulus. At all sleep stages completed motor reaction is fixed in the consciousness. However, amnesia of conditional stimulus perception and of motor reaction to it is rapidly developed, in particular in the slow-wave phase."}
{"id": "PMID:213914", "title": "[Staircase phenomenon in children with progressive muscular dystrophy and dermatomyositis].", "content": "The electrical and mechanical activity of the isometric twitch of flexor carpi ulnaris muscle during two per second indirect supramaximal stimulation for 90 sec was examined in 14 children with muscular distrophy and 8 children with dermatomyositis. The muscle electrical responses show no significant changes in the amplitude of its first negative phase. The first derivative of the dinamogram shows some of the following abnormalities in 8 of the examined children with muscular distrophy and in 2 of these with dermatomyositis: 1. Prolonged and increased negative staircase; 2. Insufficient or absent positive staircase potentiation. These abnormalities of the staircase phenomenon disclose disorders of the contractile function of the examined muscle.", "contents": "[Staircase phenomenon in children with progressive muscular dystrophy and dermatomyositis]. The electrical and mechanical activity of the isometric twitch of flexor carpi ulnaris muscle during two per second indirect supramaximal stimulation for 90 sec was examined in 14 children with muscular distrophy and 8 children with dermatomyositis. The muscle electrical responses show no significant changes in the amplitude of its first negative phase. The first derivative of the dinamogram shows some of the following abnormalities in 8 of the examined children with muscular distrophy and in 2 of these with dermatomyositis: 1. Prolonged and increased negative staircase; 2. Insufficient or absent positive staircase potentiation. These abnormalities of the staircase phenomenon disclose disorders of the contractile function of the examined muscle."}
{"id": "PMID:213915", "title": "[Electroencephalography in children with malignant neoplasms of the internal organ and support-motor apparatus].", "content": "A neurological examination of 120 patients with malignant newgrowths of a different localization and histological structure was conducted. Neurological changes due to lesions of the central and peripheral nervous systems were revealed. With the aid of EEG studies and subsequent clinico-EEG correlations 29 patients were examined. The conclusion is made that EEG studies of malformations in children allow to detect subclinical forms of brain lesions. In most of the cases there was an inadequacy between the slightly expressed cerebral symptomatology and crude changes of the EEG. The changed EEG was especially marked in primary cancer of the liver, also with normalization of the EEG in the development of positive dynamics of the main disease. The studies conducted indicate the significance of EEG in receiving thorough characteristics of the neurological changes in malignant tumors.", "contents": "[Electroencephalography in children with malignant neoplasms of the internal organ and support-motor apparatus]. A neurological examination of 120 patients with malignant newgrowths of a different localization and histological structure was conducted. Neurological changes due to lesions of the central and peripheral nervous systems were revealed. With the aid of EEG studies and subsequent clinico-EEG correlations 29 patients were examined. The conclusion is made that EEG studies of malformations in children allow to detect subclinical forms of brain lesions. In most of the cases there was an inadequacy between the slightly expressed cerebral symptomatology and crude changes of the EEG. The changed EEG was especially marked in primary cancer of the liver, also with normalization of the EEG in the development of positive dynamics of the main disease. The studies conducted indicate the significance of EEG in receiving thorough characteristics of the neurological changes in malignant tumors."}
{"id": "PMID:213911", "title": "[Detection of the critical period of pituitary-adrenal system development during postembryonic chicken ontogenesis].", "content": "Studies have been made on postembryonic development of the hypophyseal-adrenal system in domestic hens. Most significant functional rearrangements were observed at the 3rd week of life, when corticosteroid content of the blood plasma decreased threefold. Birds subjected to a series of cold stresses at this time, exhibited more rapid sexual maturation, more rapid reaction of the adrenals to exogenous corticotropin and higher resistance to unfavourable factors. Stress expositions in other days of the first month of life also resulted in trace phenomena, although these were less evident. It is suggested that the 3rd week after hatching is a critical period in the development of ihe hypophyseal-adrenal system in hens.", "contents": "[Detection of the critical period of pituitary-adrenal system development during postembryonic chicken ontogenesis]. Studies have been made on postembryonic development of the hypophyseal-adrenal system in domestic hens. Most significant functional rearrangements were observed at the 3rd week of life, when corticosteroid content of the blood plasma decreased threefold. Birds subjected to a series of cold stresses at this time, exhibited more rapid sexual maturation, more rapid reaction of the adrenals to exogenous corticotropin and higher resistance to unfavourable factors. Stress expositions in other days of the first month of life also resulted in trace phenomena, although these were less evident. It is suggested that the 3rd week after hatching is a critical period in the development of ihe hypophyseal-adrenal system in hens."}
{"id": "PMID:213912", "title": "[Synaptic ion currents in muscle fibers of Drosophila melanogaster].", "content": "The spontaneous excitatory junctional currents (e. j. c.'s) were recorded intracellulary using voltage clamp technique in experiments performed on the isolated cutaneo-muscle bag of larvae, early pupae stadium and adult fly Drosophila melanogaster. The fast miniature e. j. c.'s with mean amplitude 0.41 nA, rise time 1.60 ms and half-decay time 3.11 ms were most frequently observed. Besides these, slow miniature (half--decay time 7--20 ms) and fast giant (amplitude 12--15 nA) were sometimes present. It was found that the time course of fast e. j. c.'s is prolonged with hyperpolarisation and with the decrease in temperature. Some drugs which effectively modify the time course of end-plate currents at the cholinergic junctions (atropine, scopolamine, lidocaine, serotonin, QX-222 and ethanol) were tested. Except for ethanol, none of these drugs when added to the muscle bath affected either the amplitude or the time course of e. j. c.'s. The properties of e. j. c.'s in different neuro-muscular junctions of vertebrates and insects are discussed.", "contents": "[Synaptic ion currents in muscle fibers of Drosophila melanogaster]. The spontaneous excitatory junctional currents (e. j. c.'s) were recorded intracellulary using voltage clamp technique in experiments performed on the isolated cutaneo-muscle bag of larvae, early pupae stadium and adult fly Drosophila melanogaster. The fast miniature e. j. c.'s with mean amplitude 0.41 nA, rise time 1.60 ms and half-decay time 3.11 ms were most frequently observed. Besides these, slow miniature (half--decay time 7--20 ms) and fast giant (amplitude 12--15 nA) were sometimes present. It was found that the time course of fast e. j. c.'s is prolonged with hyperpolarisation and with the decrease in temperature. Some drugs which effectively modify the time course of end-plate currents at the cholinergic junctions (atropine, scopolamine, lidocaine, serotonin, QX-222 and ethanol) were tested. Except for ethanol, none of these drugs when added to the muscle bath affected either the amplitude or the time course of e. j. c.'s. The properties of e. j. c.'s in different neuro-muscular junctions of vertebrates and insects are discussed."}
{"id": "PMID:213913", "title": "[Several features of the metabolism of the fast and slow muscles of Emys orbicularis tortoises].", "content": "In skeletal muscles of the tortoise E. orbicularis, studies have been made on the content of glycogen, lactic acid, on the activity of glucose-6-phosphatase and phosphorylase. Histochemical studies were made on the lipid content. Experiments were performed on fast and slow bundles from mm. iliofibularis, testo cervicalis and retractor capitis. For comparison, the same indices of carbohydrate metabolism were investigated in fast m. plantaris and slow m. soleus of rats. In rats, slow muscles exhibit aerobic metabolism, in fast muscles--anaerobic one. In tortoises, slow muscles exhibit intermediate type of metabolism. Fast muscles show an anaerobic type or metabolism which is less intensive than anaerobic metabolism in slow muscles. Significant differences in some of the indices of carbohydrate metabolism were found in muscles which perform different functions in the organism.", "contents": "[Several features of the metabolism of the fast and slow muscles of Emys orbicularis tortoises]. In skeletal muscles of the tortoise E. orbicularis, studies have been made on the content of glycogen, lactic acid, on the activity of glucose-6-phosphatase and phosphorylase. Histochemical studies were made on the lipid content. Experiments were performed on fast and slow bundles from mm. iliofibularis, testo cervicalis and retractor capitis. For comparison, the same indices of carbohydrate metabolism were investigated in fast m. plantaris and slow m. soleus of rats. In rats, slow muscles exhibit aerobic metabolism, in fast muscles--anaerobic one. In tortoises, slow muscles exhibit intermediate type of metabolism. Fast muscles show an anaerobic type or metabolism which is less intensive than anaerobic metabolism in slow muscles. Significant differences in some of the indices of carbohydrate metabolism were found in muscles which perform different functions in the organism."}
{"id": "PMID:213918", "title": "Release of cyclic AMP from thyroid cells in vitro.", "content": "Half lobes of mouse thyroid gland were incubated in vitro with TSH. They released cyclic AMP (cAMP) into the medium in amounts depending on the concentration of TSH. The release of cAMP was greatest during the first hour of incubation then it occurred at a lower rate. With an incubation time of 45 min the medium cAMP levels ranged from 43.0 +/- 11.9 pmole per mg tissue protein for controls to 296.5 +/- 29.2 pmole per mg tissue protein with 5 mU of TSH in the medium. The tissue cAMP level reached a maximum after 15--30 min of incubation with TSH, then it gradually decreased towards control level during 4 h of incubation. With 25 min of incubation the tissue cAMP level was 28.5 +/- 8.8 pmole per mg tissue protein for controls compared to 194.3 +/- 27.0 pmole per mg tissue protein with 5 mU TSH in the incubation medium. The release of thyroxine was of the same order during the later part of the 4 h incubation period compared to the first one. The results illustrate the quantitative importance of cAMP release, and the fact that in the later part of the incubaion period the cell content of cAMP was low while the release of thyroxine remained high.", "contents": "Release of cyclic AMP from thyroid cells in vitro. Half lobes of mouse thyroid gland were incubated in vitro with TSH. They released cyclic AMP (cAMP) into the medium in amounts depending on the concentration of TSH. The release of cAMP was greatest during the first hour of incubation then it occurred at a lower rate. With an incubation time of 45 min the medium cAMP levels ranged from 43.0 +/- 11.9 pmole per mg tissue protein for controls to 296.5 +/- 29.2 pmole per mg tissue protein with 5 mU of TSH in the medium. The tissue cAMP level reached a maximum after 15--30 min of incubation with TSH, then it gradually decreased towards control level during 4 h of incubation. With 25 min of incubation the tissue cAMP level was 28.5 +/- 8.8 pmole per mg tissue protein for controls compared to 194.3 +/- 27.0 pmole per mg tissue protein with 5 mU TSH in the incubation medium. The release of thyroxine was of the same order during the later part of the 4 h incubation period compared to the first one. The results illustrate the quantitative importance of cAMP release, and the fact that in the later part of the incubaion period the cell content of cAMP was low while the release of thyroxine remained high."}
{"id": "PMID:213916", "title": "[Effect of serotonin on the viability of rats with transplanted glioblastoma multiforme].", "content": "Mongrel adult albino female rats with multiform glioblastoma transplanted to the right cerebellar hemisphere were given subcutaneous injections of 8 mg/kg of a serotonin-creatine sulphate solution beginning with the 3rd and to the 28th postoperative days. Rats with a tumor inoculated at the same periods and given injections of a physiological saline solution served as controls. The injection of serotonin leads to a significant increase in the survival of rats by 20% as compared to the survival of rats in the control group, but practically has no effect on the life span of sick animals. Consequently, serotonin either produces an antineoplastic effect in which case the animals do not contract the disease, or it has no effect on the tumor so that the animals die of the developing tumor. Study of the tryptophan content in the neoplasm and the 5-OIAA content in urine provides evidence of a disturbed serotonin synthesis and metabolism in these neoplasms.", "contents": "[Effect of serotonin on the viability of rats with transplanted glioblastoma multiforme]. Mongrel adult albino female rats with multiform glioblastoma transplanted to the right cerebellar hemisphere were given subcutaneous injections of 8 mg/kg of a serotonin-creatine sulphate solution beginning with the 3rd and to the 28th postoperative days. Rats with a tumor inoculated at the same periods and given injections of a physiological saline solution served as controls. The injection of serotonin leads to a significant increase in the survival of rats by 20% as compared to the survival of rats in the control group, but practically has no effect on the life span of sick animals. Consequently, serotonin either produces an antineoplastic effect in which case the animals do not contract the disease, or it has no effect on the tumor so that the animals die of the developing tumor. Study of the tryptophan content in the neoplasm and the 5-OIAA content in urine provides evidence of a disturbed serotonin synthesis and metabolism in these neoplasms."}
{"id": "PMID:213920", "title": "Primary aldosteronism: inability to differentiate unilateral from bilateral adrenal lesions by various routine clinical and laboratory data and by peripheral plasma aldosterone.", "content": "In 31 patients with primary aldosteronism routine clinical and laboratory data, the effect of orthostasis on plasma aldosterone (PA), plasma renin activity (PRA) and cortisol (PC), effect of fludrocortisone or high sodium intake on basal PA and night-day fluctuations of basal PA and PC with and without suppression of pituitary ACTH by dexamethasone were determined to differentiate patients with a unilateral aldosterone producing tumour (adenoma, APA, n=20; carcinoma, CA, n=1) from those with idiopathic bilateral adrenal hyperplasia (IAH, n=10). Mean systolic and diastolic blood pressure, age, serum potassium and urinary excretion of sodium and potassium were not significantly different in both groups of patients. Normokalaemic primary aldosteronism occurred both in patients with APA (n=2) and in patients with IAH (n=1). Mean basal PA and mean urinary excretion rate of aldosterone-18-glucuronide were higher though not significantly different in patients with APA or CA than in those with IAH. A substantial number of the patients with APA (n=5) and with IAH (n=3) showed urinary excretion rates of aldosterone-18-glucuronide less than 13 microgram/24 h. Mean PA and PRA significantly increased (P less than 0.025) in patients with IAH in response to posture. However, these changes also occurred at times in some patients with APA. Both fludrocortisone and high sodium intake produced a variable and no group-specific effect on basal PA. Night-day variations in PA were positively correlated with those in PC in all patients with APA (n=12) and in 5 of 8 patients with IAH. A dissociation of PA and PC, however, was only observed in patients with IAH. Finally, the effect of dexamethasone on plasma aldosterone curves was variable in both groups of patients. Our results indicate that under the described conditions analysis of routine clinical and laboratory data and of peripheral PA, PRA and PC are of limited value in differentiating patients with APA or CA from those with IAH.", "contents": "Primary aldosteronism: inability to differentiate unilateral from bilateral adrenal lesions by various routine clinical and laboratory data and by peripheral plasma aldosterone. In 31 patients with primary aldosteronism routine clinical and laboratory data, the effect of orthostasis on plasma aldosterone (PA), plasma renin activity (PRA) and cortisol (PC), effect of fludrocortisone or high sodium intake on basal PA and night-day fluctuations of basal PA and PC with and without suppression of pituitary ACTH by dexamethasone were determined to differentiate patients with a unilateral aldosterone producing tumour (adenoma, APA, n=20; carcinoma, CA, n=1) from those with idiopathic bilateral adrenal hyperplasia (IAH, n=10). Mean systolic and diastolic blood pressure, age, serum potassium and urinary excretion of sodium and potassium were not significantly different in both groups of patients. Normokalaemic primary aldosteronism occurred both in patients with APA (n=2) and in patients with IAH (n=1). Mean basal PA and mean urinary excretion rate of aldosterone-18-glucuronide were higher though not significantly different in patients with APA or CA than in those with IAH. A substantial number of the patients with APA (n=5) and with IAH (n=3) showed urinary excretion rates of aldosterone-18-glucuronide less than 13 microgram/24 h. Mean PA and PRA significantly increased (P less than 0.025) in patients with IAH in response to posture. However, these changes also occurred at times in some patients with APA. Both fludrocortisone and high sodium intake produced a variable and no group-specific effect on basal PA. Night-day variations in PA were positively correlated with those in PC in all patients with APA (n=12) and in 5 of 8 patients with IAH. A dissociation of PA and PC, however, was only observed in patients with IAH. Finally, the effect of dexamethasone on plasma aldosterone curves was variable in both groups of patients. Our results indicate that under the described conditions analysis of routine clinical and laboratory data and of peripheral PA, PRA and PC are of limited value in differentiating patients with APA or CA from those with IAH."}
{"id": "PMID:213921", "title": "Cholinergic influences on hypothalamic-pituitary-adrenocortical activity of stressed rats: an approach utilizing choline deficient diets.", "content": "Male rats were placed on choline (Ch) deficient diets for 3 to 14 days, without and with Ch (normal and large doses) supplemented in the drinking water, to determine whether altering the availability of Ch would affect the cholinergic system in relation to the latter's role in modulating the hypothalamic-pituitary-adrenocortical (HPA) system of non-stressed and stressed animals. The results indicate that the basal nonstressed activity of the HPA system, as assessed by adrenal and plasma corticosterone concentrations, was not affected by placing the animals on these diets for as long as 14 days. Furthermore, the in vitro production of corticosterone by these adrenal glands, in the presence or absence of adrenocorticotrophin, was similar to those observed in animals on the regular rat diet; however, the HPA responses to auditory (100 db) stress, and to a lesser extent hypercapnic (9% CO2) stress, were impaired on the Ch deficient diet (14 days), and these responses were partially corrected by supplementing the diet with Ch in the drinking water. Thus, the data suggest that altering the dietary intake of Ch may affect cholinergic activity, which in turn affects the HPA response to stressors.", "contents": "Cholinergic influences on hypothalamic-pituitary-adrenocortical activity of stressed rats: an approach utilizing choline deficient diets. Male rats were placed on choline (Ch) deficient diets for 3 to 14 days, without and with Ch (normal and large doses) supplemented in the drinking water, to determine whether altering the availability of Ch would affect the cholinergic system in relation to the latter's role in modulating the hypothalamic-pituitary-adrenocortical (HPA) system of non-stressed and stressed animals. The results indicate that the basal nonstressed activity of the HPA system, as assessed by adrenal and plasma corticosterone concentrations, was not affected by placing the animals on these diets for as long as 14 days. Furthermore, the in vitro production of corticosterone by these adrenal glands, in the presence or absence of adrenocorticotrophin, was similar to those observed in animals on the regular rat diet; however, the HPA responses to auditory (100 db) stress, and to a lesser extent hypercapnic (9% CO2) stress, were impaired on the Ch deficient diet (14 days), and these responses were partially corrected by supplementing the diet with Ch in the drinking water. Thus, the data suggest that altering the dietary intake of Ch may affect cholinergic activity, which in turn affects the HPA response to stressors."}
{"id": "PMID:213923", "title": "Evaluation of the endocrine functions in dystrophia myotonica.", "content": "Investigation of several endocrine functions was performed in seven patients with dystrophia myotonica (DM). All patients had hyperinsulinemia. Whereas the four female patients had normal pituitary-gonadal function, all three male patients presented evidence of a primary gonadal failure. Thyroid function was normal in all patients. Four patients displayed abnormal diurnal variations of cortisol secretion. Basal prolactin levels were elevated in three patients, one of whom also had consistently elevated levels of growth hormone. The investigation adds some new evidence of neuroendocrine dysfunction at the hypothalamic level in DM.", "contents": "Evaluation of the endocrine functions in dystrophia myotonica. Investigation of several endocrine functions was performed in seven patients with dystrophia myotonica (DM). All patients had hyperinsulinemia. Whereas the four female patients had normal pituitary-gonadal function, all three male patients presented evidence of a primary gonadal failure. Thyroid function was normal in all patients. Four patients displayed abnormal diurnal variations of cortisol secretion. Basal prolactin levels were elevated in three patients, one of whom also had consistently elevated levels of growth hormone. The investigation adds some new evidence of neuroendocrine dysfunction at the hypothalamic level in DM."}
{"id": "PMID:213924", "title": "Conduction along the articular branch of the suprascapular nerve.", "content": "The maximum sensory conduction velocity was measured along the articular branch of the suprascapular nerve. The potential was evoked by stimulating in the perception area of the nerve above the glenohumeral joint and recorded by an electrode near the suprascapular nerve in the supraclavicular fossa. The maximum conduction velocity averaged 42 m/s, SD 4.6 m/s (20 normal subjects); it decreased slightly with age. When correcting for the error in distance arising from the measurement by obstetric calipers (20%), the maximum conduction velocity averaged 50 m/s. The peak-to-peak amplitude of the main component of the sensory potential was 0.8 muV, SD 0.5 muV. In one of seven patients with a pain syndrome in the shoulder secondary to a brachial plexus neuropathy the velocity and the amplitude of the sensory potential was diminished. In five other patients with pain in the region of the shoulder the conduction velocity was normal but the amplitude was diminished.", "contents": "Conduction along the articular branch of the suprascapular nerve. The maximum sensory conduction velocity was measured along the articular branch of the suprascapular nerve. The potential was evoked by stimulating in the perception area of the nerve above the glenohumeral joint and recorded by an electrode near the suprascapular nerve in the supraclavicular fossa. The maximum conduction velocity averaged 42 m/s, SD 4.6 m/s (20 normal subjects); it decreased slightly with age. When correcting for the error in distance arising from the measurement by obstetric calipers (20%), the maximum conduction velocity averaged 50 m/s. The peak-to-peak amplitude of the main component of the sensory potential was 0.8 muV, SD 0.5 muV. In one of seven patients with a pain syndrome in the shoulder secondary to a brachial plexus neuropathy the velocity and the amplitude of the sensory potential was diminished. In five other patients with pain in the region of the shoulder the conduction velocity was normal but the amplitude was diminished."}
{"id": "PMID:213926", "title": "Ultrastructural sequence of myelin degradation. II. Wallerian degeneration in the rat femoral nerve.", "content": "Myelin degradation in Wallerian degeneration of rat femoral nerves has been studied with the electron microscope. In the initial stages, a decrease of myelin periodicity from 115 A to 88 A was noted, followed by the transformation of the myelin structure into uniformly layered lipid inclusions. 10--14 days after nerve section, most of the inclusions found represented unstructured lipid droplets or crystals. In the later stages of degeneration, numerous pleomorphic lamellar inclusions were found, some of them resembling the structure of pi and micron-granules. Lysosomal enzyme activity was found especially in pleomorphic inclusions during the late stages of myelin degradation. Normal myelin sheaths, as well as unstructured lipid droplets and crystals, were devoid of enzyme activity. The results are compared with alterations found in Wallerian degeneration of the central nervous system.", "contents": "Ultrastructural sequence of myelin degradation. II. Wallerian degeneration in the rat femoral nerve. Myelin degradation in Wallerian degeneration of rat femoral nerves has been studied with the electron microscope. In the initial stages, a decrease of myelin periodicity from 115 A to 88 A was noted, followed by the transformation of the myelin structure into uniformly layered lipid inclusions. 10--14 days after nerve section, most of the inclusions found represented unstructured lipid droplets or crystals. In the later stages of degeneration, numerous pleomorphic lamellar inclusions were found, some of them resembling the structure of pi and micron-granules. Lysosomal enzyme activity was found especially in pleomorphic inclusions during the late stages of myelin degradation. Normal myelin sheaths, as well as unstructured lipid droplets and crystals, were devoid of enzyme activity. The results are compared with alterations found in Wallerian degeneration of the central nervous system."}
{"id": "PMID:213927", "title": "Microtubules observed within the cistern of RER in neurons of the aged dog.", "content": "Twenty-seven randomly selected dogs ranging from 1 month to 16 years of age were examined light- and electron microscopically. An intraneuronal inclusion body was found im 13 of 27 cases. In particular, 12 of 13 positive cases were elderly dogs of over 8 years of age. The inclusions showed amphophilic violet color with H.-E. stain and measured 3--42 micrometer in diameter. Histochemically, they were thought to be a glycoprotein complex. The inclusions were characterized by the electron microscopy and composed of aggregated cistern of RER closely packed with tubular structures. The individual tubules measured about 24 nm in diameter and had 11--13 subunits forming their walls. These constituents were very similar to those of microtubules. The occurrence of the inclusion bodies showed an apparent age-dependency.", "contents": "Microtubules observed within the cistern of RER in neurons of the aged dog. Twenty-seven randomly selected dogs ranging from 1 month to 16 years of age were examined light- and electron microscopically. An intraneuronal inclusion body was found im 13 of 27 cases. In particular, 12 of 13 positive cases were elderly dogs of over 8 years of age. The inclusions showed amphophilic violet color with H.-E. stain and measured 3--42 micrometer in diameter. Histochemically, they were thought to be a glycoprotein complex. The inclusions were characterized by the electron microscopy and composed of aggregated cistern of RER closely packed with tubular structures. The individual tubules measured about 24 nm in diameter and had 11--13 subunits forming their walls. These constituents were very similar to those of microtubules. The occurrence of the inclusion bodies showed an apparent age-dependency."}
{"id": "PMID:213928", "title": "Ultrastructural sequence of myelin degradation. I. Wallerian degeneration in the rat optic nerve.", "content": "The ultrastructural events in myelin degradation in the rat optic nerve following transection have been studied. Myelin debris was found in cells similar to multipotential glia cells (Vaughn and Peters, 1968) as well as in astrocytes and in few oligodendrocytes. The different types of inclusions found during myelin degradation were described in their quantitative relations. Similarities to inclusions described in adrenoleukodystrophy adn multiple sclerosis are discussed. By comparison of the ultrastructural findings with histochemical and biochemical data available a hypothetical model of myelin degradation is presented. The process starts with the degradation of digestible proteins resulting in uniformly layered lipid inclusions. Lipid degradation leads to the formation of unstructured lipid droplets and crystals. During the late stages of Wallerian degeneration numerous polymorph inclusion typed can be found, probably representing poorly digestible lipids or lipoproteins.", "contents": "Ultrastructural sequence of myelin degradation. I. Wallerian degeneration in the rat optic nerve. The ultrastructural events in myelin degradation in the rat optic nerve following transection have been studied. Myelin debris was found in cells similar to multipotential glia cells (Vaughn and Peters, 1968) as well as in astrocytes and in few oligodendrocytes. The different types of inclusions found during myelin degradation were described in their quantitative relations. Similarities to inclusions described in adrenoleukodystrophy adn multiple sclerosis are discussed. By comparison of the ultrastructural findings with histochemical and biochemical data available a hypothetical model of myelin degradation is presented. The process starts with the degradation of digestible proteins resulting in uniformly layered lipid inclusions. Lipid degradation leads to the formation of unstructured lipid droplets and crystals. During the late stages of Wallerian degeneration numerous polymorph inclusion typed can be found, probably representing poorly digestible lipids or lipoproteins."}
{"id": "PMID:213931", "title": "Selenium and vitamin E in cord blood from preterm and full term infants.", "content": "Selenium was determined in erythrocytes and serum, and vitamin E and beta-lipoprotein in serum from cord blood samples of 31 full term and 20 preterm infants. Venous samples from 21 mothers at birth and 15 normal adult women were also analyzed. No difference for either selenium or vitamin E was found between the preterm and full term infants. The selenium concentration in red blood cells was the same for newborn, mothers at birth, and normal adult women. The serum concentration of selenium was, however, significantly lower in the newborn, the mean level in the children being 64% of that in the mothers. The level in the mothers did not differ from that in non-pregnant women. The vitamin E concentration was found to correlate very well with the beta-lipoprotein concentration. This indicates that differences in the transport capacity account for the large difference in the serum tocopherol levels of mothers at birth and newborn.", "contents": "Selenium and vitamin E in cord blood from preterm and full term infants. Selenium was determined in erythrocytes and serum, and vitamin E and beta-lipoprotein in serum from cord blood samples of 31 full term and 20 preterm infants. Venous samples from 21 mothers at birth and 15 normal adult women were also analyzed. No difference for either selenium or vitamin E was found between the preterm and full term infants. The selenium concentration in red blood cells was the same for newborn, mothers at birth, and normal adult women. The serum concentration of selenium was, however, significantly lower in the newborn, the mean level in the children being 64% of that in the mothers. The level in the mothers did not differ from that in non-pregnant women. The vitamin E concentration was found to correlate very well with the beta-lipoprotein concentration. This indicates that differences in the transport capacity account for the large difference in the serum tocopherol levels of mothers at birth and newborn."}
{"id": "PMID:213932", "title": "Hepatic sarcoma associated with hepatoma.", "content": "An autopsy case with simultaneous occurrence of hepatoma and spindle cell sarcoma in the liver was presented. These tumors arose in the left and right lobes and showed no continuity. The sarcoma metastasized in hilar lymph node of the liver and in the cervical and lumbar vertebrae, but no metastasis of the hepatoma was found except in the opposite lobe of the liver. Literature on such combinations was briefly reviewed.", "contents": "Hepatic sarcoma associated with hepatoma. An autopsy case with simultaneous occurrence of hepatoma and spindle cell sarcoma in the liver was presented. These tumors arose in the left and right lobes and showed no continuity. The sarcoma metastasized in hilar lymph node of the liver and in the cervical and lumbar vertebrae, but no metastasis of the hepatoma was found except in the opposite lobe of the liver. Literature on such combinations was briefly reviewed."}
{"id": "PMID:213933", "title": "Hepatocellular carcinoma and myocardial sarcoidosis.--An autopsy case.", "content": "An autopsy case of a 65-year-old male who died of hepatocellular carcinoma superimposed on liver cirrhosis complicated with systemic sarcoidosis is presented. No organ metastasis of hepatocellular carcinoma was found except for a minute tumor embolus in the left upper lobe of the lung. Involved organs by sarcoidosis were the lymph nodes, lungs, heart, liver and spleen, but its presence was not noticed before death. Its cardiac involvement coincide with his clinical symptom of exertional dyspnea and the ECG finding of A-V block.", "contents": "Hepatocellular carcinoma and myocardial sarcoidosis.--An autopsy case. An autopsy case of a 65-year-old male who died of hepatocellular carcinoma superimposed on liver cirrhosis complicated with systemic sarcoidosis is presented. No organ metastasis of hepatocellular carcinoma was found except for a minute tumor embolus in the left upper lobe of the lung. Involved organs by sarcoidosis were the lymph nodes, lungs, heart, liver and spleen, but its presence was not noticed before death. Its cardiac involvement coincide with his clinical symptom of exertional dyspnea and the ECG finding of A-V block."}
{"id": "PMID:213934", "title": "Comparison of small hepatitis B surface antigen particles and human serum low density lipoprotein molecules by electron microscopy.", "content": "The small spherical particles associated with hepatitis B surface antigen (HBsAg) could be distinguished from the low density lipoprotein (LDL) molecules in human serum by examination of coded, negatively stained preparations. The HBsAg associated particles showed a more marked contrast against the background than LDL. Addition of specific antiserum to LDL caused a significantly reduced mean diameter of LDL molecules. An insignificant reduction in size of HBsAg particles was found by corresponding treatment. It is suggested that the antibody molecules protect LDL molecules protect LDL molecules against artificial flattening during preparation.", "contents": "Comparison of small hepatitis B surface antigen particles and human serum low density lipoprotein molecules by electron microscopy. The small spherical particles associated with hepatitis B surface antigen (HBsAg) could be distinguished from the low density lipoprotein (LDL) molecules in human serum by examination of coded, negatively stained preparations. The HBsAg associated particles showed a more marked contrast against the background than LDL. Addition of specific antiserum to LDL caused a significantly reduced mean diameter of LDL molecules. An insignificant reduction in size of HBsAg particles was found by corresponding treatment. It is suggested that the antibody molecules protect LDL molecules protect LDL molecules against artificial flattening during preparation."}
{"id": "PMID:213935", "title": "beta-Adrenoceptor stimulation of the human urinary bladder in vivo.", "content": "The effect of beta-adrenorecptor stimulation on the volume of the urinary bladder in 16 neurologically normal humans without symptoms of micturition disturbances was investigated. Terbutaline, a selective beta2-adrenoceptor stimulating agent, was tested in 9 persons and isoprenaline, a general beta-adrenoceptor stimulating agent, was tested in 7 persons. After terbutaline the maximum increase in the bladder volume was 10% and on an average aroung 5%. After isoprenaline the maximum increase in the bladder volume was 15% and on an average around 5%. Terbutaline as well as isoprenaline administration resulted in tachycardia and an increased pulse pressure. The tachycardia was somewhat more marked after isoprenaline. In conclusion, only a small increase in the volume of the urinary bladder was noted after beta-adrenoceptor stimulation in neurologically normal humans without symptoms of micturition disturbances, in contrast to effects achieved in some patients with urgency. Terbutaline seems to have less cardiac effects compared to isoprenaline and is therefore to be preferred when beta-adrenoceptor stimulation is required in patients with urgency.", "contents": "beta-Adrenoceptor stimulation of the human urinary bladder in vivo. The effect of beta-adrenorecptor stimulation on the volume of the urinary bladder in 16 neurologically normal humans without symptoms of micturition disturbances was investigated. Terbutaline, a selective beta2-adrenoceptor stimulating agent, was tested in 9 persons and isoprenaline, a general beta-adrenoceptor stimulating agent, was tested in 7 persons. After terbutaline the maximum increase in the bladder volume was 10% and on an average aroung 5%. After isoprenaline the maximum increase in the bladder volume was 15% and on an average around 5%. Terbutaline as well as isoprenaline administration resulted in tachycardia and an increased pulse pressure. The tachycardia was somewhat more marked after isoprenaline. In conclusion, only a small increase in the volume of the urinary bladder was noted after beta-adrenoceptor stimulation in neurologically normal humans without symptoms of micturition disturbances, in contrast to effects achieved in some patients with urgency. Terbutaline seems to have less cardiac effects compared to isoprenaline and is therefore to be preferred when beta-adrenoceptor stimulation is required in patients with urgency."}
{"id": "PMID:213936", "title": "Differences in postsynaptic alpha-adrenoceptor populations between isolated cat urethra and various other isolated tissues.", "content": "This study was undertaken with the aim of determining whether the postsynaptic alpha-adrenergic receptor population of the cat urethra differed from that of other isolated tissues (rabbit aorta and rat vas deferens) and if so the possibility of selectively affect these receptors. For this purpose the substances 2-methylammonio-1-(spiro[cyclopentane-1,1'-indene]-3'-yl)ethanol (KABI 2023), noradrenaline (NA) and dopamine (DA) were used. KABI 2023 and NA acted as full agonists on all three tissues investigated. DA was a full agonist on the vas deferens but was almost inactive on urethra. The contractile response of urethra to KABI 2023 was of an alpha-adrenergic nature, as it could be blocked with phentolamine. Compared with NA, KABI 2023 showed a 10 times higher selectivity for the receptors of urethra than for those of aorta. Affinity constants (log KB) for phentolamine and haloperidol with use of the various agonists were estimated. The affinity of phentolamine was found to be significantly different when using NA and KABI 2023 as agonists on the urethra but not on the aorta. Corresponding findings were obtained with haloperidol. On the vas deferens a greater difference in log KB values than that on the urethra was found. On the basis of the results, it is suggested that the population of postsynaptic alpha-adrenoceptors in the urethra (cat) differs from that in the aorta (rabbit). On the vas deferens a heterogenicity of postsynaptic receptors seem to exist which makes the interpretation of the results more difficult on this organ. In the presence of phentolamine and haloperidol the maximum responses to NA were potentiated on the aorta and vas deferens, but not on the urethra. Investigations to evaluate this difference are now in progress.", "contents": "Differences in postsynaptic alpha-adrenoceptor populations between isolated cat urethra and various other isolated tissues. This study was undertaken with the aim of determining whether the postsynaptic alpha-adrenergic receptor population of the cat urethra differed from that of other isolated tissues (rabbit aorta and rat vas deferens) and if so the possibility of selectively affect these receptors. For this purpose the substances 2-methylammonio-1-(spiro[cyclopentane-1,1'-indene]-3'-yl)ethanol (KABI 2023), noradrenaline (NA) and dopamine (DA) were used. KABI 2023 and NA acted as full agonists on all three tissues investigated. DA was a full agonist on the vas deferens but was almost inactive on urethra. The contractile response of urethra to KABI 2023 was of an alpha-adrenergic nature, as it could be blocked with phentolamine. Compared with NA, KABI 2023 showed a 10 times higher selectivity for the receptors of urethra than for those of aorta. Affinity constants (log KB) for phentolamine and haloperidol with use of the various agonists were estimated. The affinity of phentolamine was found to be significantly different when using NA and KABI 2023 as agonists on the urethra but not on the aorta. Corresponding findings were obtained with haloperidol. On the vas deferens a greater difference in log KB values than that on the urethra was found. On the basis of the results, it is suggested that the population of postsynaptic alpha-adrenoceptors in the urethra (cat) differs from that in the aorta (rabbit). On the vas deferens a heterogenicity of postsynaptic receptors seem to exist which makes the interpretation of the results more difficult on this organ. In the presence of phentolamine and haloperidol the maximum responses to NA were potentiated on the aorta and vas deferens, but not on the urethra. Investigations to evaluate this difference are now in progress."}
{"id": "PMID:213938", "title": "Cholinergic mechanisms in the rat detrusor muscle.", "content": "The motor response of the urinary bladder to nerve stimulation is resistant to atropine, and it has been proposed that the nerves are non-cholinergic, but are possibly purinergic. In this review evidence is presented suggesting a cholinergic transmission in the rat detrusor muscle, part of the receptors being inaccessible to atropine. The rat bladder receives postganglionic cholinergic fibres not only from the pelvic but also from the hypogastric nerves, some fibres passing outside the pelvic ganglia and some relaying distal to them. There is a functional overlap between the right and the left pelvic nerve, but the contractile response to stimulation of the hypogastric nerves is added to the pelvic nerve response with no functional overlap or antagonism.", "contents": "Cholinergic mechanisms in the rat detrusor muscle. The motor response of the urinary bladder to nerve stimulation is resistant to atropine, and it has been proposed that the nerves are non-cholinergic, but are possibly purinergic. In this review evidence is presented suggesting a cholinergic transmission in the rat detrusor muscle, part of the receptors being inaccessible to atropine. The rat bladder receives postganglionic cholinergic fibres not only from the pelvic but also from the hypogastric nerves, some fibres passing outside the pelvic ganglia and some relaying distal to them. There is a functional overlap between the right and the left pelvic nerve, but the contractile response to stimulation of the hypogastric nerves is added to the pelvic nerve response with no functional overlap or antagonism."}
{"id": "PMID:213939", "title": "The effects of anticholinergics on the urinary bladder mechanism.", "content": "A summary is given of the physiological conditions concerned with collection and expulsion of urine from the bladder. The role of afferent and efferent nerve activity from and to the urinary bladder and urethra is discussed. When studying the effects of anticholinergics on the urinary bladder in animals an in situ model described here seems to be the most valid for conditions in man. This method involves recording of the intravesical pressure in conscious rabbits stimultaneously with a bladder infusion. An assessment is made of the evidence for a purinergic transmission in the urinary bladder.", "contents": "The effects of anticholinergics on the urinary bladder mechanism. A summary is given of the physiological conditions concerned with collection and expulsion of urine from the bladder. The role of afferent and efferent nerve activity from and to the urinary bladder and urethra is discussed. When studying the effects of anticholinergics on the urinary bladder in animals an in situ model described here seems to be the most valid for conditions in man. This method involves recording of the intravesical pressure in conscious rabbits stimultaneously with a bladder infusion. An assessment is made of the evidence for a purinergic transmission in the urinary bladder."}
{"id": "PMID:213940", "title": "Methodological aspects on drug receptor binding analysis.", "content": "Although drug receptors occur in relatively low concentrations, they can be visualized by the use of appropriate radioindicators. In most cases the procedure is rapid and can reach a high degree of accuracy. Specificity of the interaction is studied by competition analysis. The necessity of using several radioindicators to define a receptor population is emphasized. It may be possible to define isorecptors and drugs with selectivity for one isoreceptor.", "contents": "Methodological aspects on drug receptor binding analysis. Although drug receptors occur in relatively low concentrations, they can be visualized by the use of appropriate radioindicators. In most cases the procedure is rapid and can reach a high degree of accuracy. Specificity of the interaction is studied by competition analysis. The necessity of using several radioindicators to define a receptor population is emphasized. It may be possible to define isorecptors and drugs with selectivity for one isoreceptor."}
{"id": "PMID:213941", "title": "Metabolism of zearalenone in rat liver.", "content": "The metabolism of zearalenone in rat liver has been investigated. The studies were performed mainly with liver homogenate, though isolated microsomes and hepatocytes have also been used. Zearalenone was metabolized along two principal pathways, conjugation with glucuronic acid, which was the main route and reduction to an isomer of zearalenol. In no case, however, could all zearalenone metabolized be accounted for as conjugated zearalenone and free and conjugated zearalenol. Therefore another, so far unknown metabolite cannot be excluded. Reduction to zearalenol could be increased three times by the addition of NADH (or NADPH) and is probably catalyzed by a hydroxysteroid dehydrogenase. Some 25-50 per cent of the zearalenol could be conjugated, depending on the incubation conditions. The capacity of hepatocytes to eliminate zearalenone was estimated to be about 100 microgram per gram of liver in one hour. With a liver homogenate the highest value obtained was 82 microgram.", "contents": "Metabolism of zearalenone in rat liver. The metabolism of zearalenone in rat liver has been investigated. The studies were performed mainly with liver homogenate, though isolated microsomes and hepatocytes have also been used. Zearalenone was metabolized along two principal pathways, conjugation with glucuronic acid, which was the main route and reduction to an isomer of zearalenol. In no case, however, could all zearalenone metabolized be accounted for as conjugated zearalenone and free and conjugated zearalenol. Therefore another, so far unknown metabolite cannot be excluded. Reduction to zearalenol could be increased three times by the addition of NADH (or NADPH) and is probably catalyzed by a hydroxysteroid dehydrogenase. Some 25-50 per cent of the zearalenol could be conjugated, depending on the incubation conditions. The capacity of hepatocytes to eliminate zearalenone was estimated to be about 100 microgram per gram of liver in one hour. With a liver homogenate the highest value obtained was 82 microgram."}
{"id": "PMID:213942", "title": "Beta-adrenoceptor stimulation and cyclic AMP levels in bovine tracheal muscle of old and young animals.", "content": "The relationship between cyclic AMP levels and mechanical activity after exposure to isoprenaline was studied in tracheal smooth muscle. It was found that the basal cyclic AMP content decreased with age. The relaxing effects of isoprenaline, theophylline and papaverine were tested on muscles contracted by histamine, acetylcholine or carbacholine. Isoprenaline completely relaxed histamine contracted tracheas, but not those contracted by acetylcholine or carbacholine. Theophylline and papaverine completely relaxed the tracheas irrespective of whether the contracting agent was histamine, acetylcholine or carbacholine. Isoprenaline increased the cyclic AMP content of bovine trachea; this effect was stronger in muscles with spontaneous tension than in histamine contracted muscles. In muscles contracted by carbachol, isoprenaline increased the cyclic AMP level after 5 min. The correlations between the changes in the cyclic AMP levels and the tension in tracheal smooth muscle support the hypothesis that this nucleotide plays a role in the relaxation process.", "contents": "Beta-adrenoceptor stimulation and cyclic AMP levels in bovine tracheal muscle of old and young animals. The relationship between cyclic AMP levels and mechanical activity after exposure to isoprenaline was studied in tracheal smooth muscle. It was found that the basal cyclic AMP content decreased with age. The relaxing effects of isoprenaline, theophylline and papaverine were tested on muscles contracted by histamine, acetylcholine or carbacholine. Isoprenaline completely relaxed histamine contracted tracheas, but not those contracted by acetylcholine or carbacholine. Theophylline and papaverine completely relaxed the tracheas irrespective of whether the contracting agent was histamine, acetylcholine or carbacholine. Isoprenaline increased the cyclic AMP content of bovine trachea; this effect was stronger in muscles with spontaneous tension than in histamine contracted muscles. In muscles contracted by carbachol, isoprenaline increased the cyclic AMP level after 5 min. The correlations between the changes in the cyclic AMP levels and the tension in tracheal smooth muscle support the hypothesis that this nucleotide plays a role in the relaxation process."}
{"id": "PMID:213944", "title": "Effect of lowering of the temperature on the tissue levels of cAMP, cGMP, PGE and PGF2 alpha in spontaneously beating rat atria preparation.", "content": "Tissue levels of cAMP, cGMP, PGE, and PGF2 alpha were measured in spontaneously beating rat atria preparation at 20C and 37C. At 20C the formation of cAMP increased in correlation with the markedly increased amplitude and reduced frequency. The other biochemical parameters were not significantly affected by the low temperature.", "contents": "Effect of lowering of the temperature on the tissue levels of cAMP, cGMP, PGE and PGF2 alpha in spontaneously beating rat atria preparation. Tissue levels of cAMP, cGMP, PGE, and PGF2 alpha were measured in spontaneously beating rat atria preparation at 20C and 37C. At 20C the formation of cAMP increased in correlation with the markedly increased amplitude and reduced frequency. The other biochemical parameters were not significantly affected by the low temperature."}
{"id": "PMID:213945", "title": "Activity of acid hydrolases in skeletal muscle of untrained, trained and detrained mice of different ages.", "content": "The activities of p-nitrophenylphosphatase, beta-glucuronidase and beta-N-acetylglucosaminidase from crude skeletal muscle homogenates of 4 and 7 months old mice were assayed after short-term intensive and long-term moderate training and after terminated training. In the older untrained mice the activity of the hydrolases was higher than in the younger mice. The level increased with training and this increase was far more pronounced in the older animals. Cessation of training for 7 and 21 days decreased this activity in the older animals but it was again increased 42 days later and close to the level observed in the trained mice. In young mice 3 days' terminated training increased the activity of the acid hydrolases above the level of the trained animals but after additional 4 and 11 days' terminated training the activity decreased to slightly below that of the trained mice. The changes were most prominent in the activity of beta-glucuronidase and to a lesser extent in that of beta-N-acetylglucosaminidase while p-nitrophenylphosphatase activity was almost unaffected by training or terminated training. The effects of terminated training can be intepreted as representing altered catabolic processes in the turn-over of tissue components of skeletal muscle.", "contents": "Activity of acid hydrolases in skeletal muscle of untrained, trained and detrained mice of different ages. The activities of p-nitrophenylphosphatase, beta-glucuronidase and beta-N-acetylglucosaminidase from crude skeletal muscle homogenates of 4 and 7 months old mice were assayed after short-term intensive and long-term moderate training and after terminated training. In the older untrained mice the activity of the hydrolases was higher than in the younger mice. The level increased with training and this increase was far more pronounced in the older animals. Cessation of training for 7 and 21 days decreased this activity in the older animals but it was again increased 42 days later and close to the level observed in the trained mice. In young mice 3 days' terminated training increased the activity of the acid hydrolases above the level of the trained animals but after additional 4 and 11 days' terminated training the activity decreased to slightly below that of the trained mice. The changes were most prominent in the activity of beta-glucuronidase and to a lesser extent in that of beta-N-acetylglucosaminidase while p-nitrophenylphosphatase activity was almost unaffected by training or terminated training. The effects of terminated training can be intepreted as representing altered catabolic processes in the turn-over of tissue components of skeletal muscle."}
{"id": "PMID:213947", "title": "The intestinal phosphate transport under condition of experimental hypercalcemia.", "content": "The analysis of the serum calcium and phosphate level changes in intact Vitamin D--dosed animals showed the increasing serum calcium values without any concomitant change in serum phosphate concentration. The observed discrepancy of intestinal phosphate transport in vitro and in vivo studies together with the effect of Vitamin D towards normalizing serum phosphate level in TPTX Vitamin D--dosed animals suggest the presence of Vitamin D as some phosphate regulatory factor. The participation of the possible role of 25 OH D3 in the observed phenomenon is under current investigations. In PTH supressed hypercalcemic conditions we did not reproduce, with the usage of 1alpha--OH D3, the regulatory effect of 1,25 (OH) 2D3 described by Garabedian et al. /1/.", "contents": "The intestinal phosphate transport under condition of experimental hypercalcemia. The analysis of the serum calcium and phosphate level changes in intact Vitamin D--dosed animals showed the increasing serum calcium values without any concomitant change in serum phosphate concentration. The observed discrepancy of intestinal phosphate transport in vitro and in vivo studies together with the effect of Vitamin D towards normalizing serum phosphate level in TPTX Vitamin D--dosed animals suggest the presence of Vitamin D as some phosphate regulatory factor. The participation of the possible role of 25 OH D3 in the observed phenomenon is under current investigations. In PTH supressed hypercalcemic conditions we did not reproduce, with the usage of 1alpha--OH D3, the regulatory effect of 1,25 (OH) 2D3 described by Garabedian et al. /1/."}
{"id": "PMID:213961", "title": "Benign multilocal cystic nephroma.", "content": "Three cases of multilocular cystic nephroma are described. This entity differs from congenital multicystic kidney and adult polycystic disease in that it involves only a segment of one kidney. While the excretory urogram, nephrotomogram, and arteriogram show the lesion to be primarily avascular, the two cases studied by ultrasound were predominantly solid. This finding is felt to relate to the small size of the cysts as well as the presence of some solid primitive components. Because it is difficult to differentiate this lesion from an avascular renal carcinoma, surgical biopsy should be considered to help avoid a needless nephrectomy.", "contents": "Benign multilocal cystic nephroma. Three cases of multilocular cystic nephroma are described. This entity differs from congenital multicystic kidney and adult polycystic disease in that it involves only a segment of one kidney. While the excretory urogram, nephrotomogram, and arteriogram show the lesion to be primarily avascular, the two cases studied by ultrasound were predominantly solid. This finding is felt to relate to the small size of the cysts as well as the presence of some solid primitive components. Because it is difficult to differentiate this lesion from an avascular renal carcinoma, surgical biopsy should be considered to help avoid a needless nephrectomy."}
{"id": "PMID:213964", "title": "Detection of B-lymphocyte (B-cell)-associated antigens on human leukemic lymphocytes. Masking of membrane antigens.", "content": "An indirect immunofluorescent technic has been used for rabbit antisera (anti-EP) that demonstrated complement-dependent cytotoxicity against human leukemic lymphocytes but not against normal blood lymphocytes. With the immunofluorescent technic, the antisera were found to react with 2--23% of normal blood lymphocytes. Simultaneous staining of normal cells with anti-EP and for surface immunoglobulins (SIg) on bone-marrow-derived B-cells showed that the proportions of stained cells were similar to percentages of cells stained by anti-EP alone or for SIg alone. The percentage of anti-EP reactive cells also approximated the percentages of cells reactive to a known antiserum to human B-cell associated, or Ia-like, antigens. The anti-EP reacted with lymphoblastoid cells from two B-cell lines lacking the Epstein-Barr viral genome. The antigens detected by anti-EP probably are B-cell-associated. The anti-EP intensely stained neoplastic cells of acute or chronic lymphocytic leukemia and lymphosarcoma-cell leukemia. Cells from two patients with chronic lymphocytic leukemia and from two patients with acute lymphocytic leukemia showed increased intensity of anti-EP staining and/or increased proportions of stained cells following overnight incubation in culture medium, compared with the preincubation samples. This observation suggests the presence of a \"blocking component(s)\" on cell surfaces, which interfered with anti-EP reactivity. After overnight incubation, the component might have been removed from the antigenic sites on cell surfaces. Further studies of leukemia lymphocytes using anti-EP for the cell-bound \"blocking component\" may reveal important pathogenetic mechanisms.", "contents": "Detection of B-lymphocyte (B-cell)-associated antigens on human leukemic lymphocytes. Masking of membrane antigens. An indirect immunofluorescent technic has been used for rabbit antisera (anti-EP) that demonstrated complement-dependent cytotoxicity against human leukemic lymphocytes but not against normal blood lymphocytes. With the immunofluorescent technic, the antisera were found to react with 2--23% of normal blood lymphocytes. Simultaneous staining of normal cells with anti-EP and for surface immunoglobulins (SIg) on bone-marrow-derived B-cells showed that the proportions of stained cells were similar to percentages of cells stained by anti-EP alone or for SIg alone. The percentage of anti-EP reactive cells also approximated the percentages of cells reactive to a known antiserum to human B-cell associated, or Ia-like, antigens. The anti-EP reacted with lymphoblastoid cells from two B-cell lines lacking the Epstein-Barr viral genome. The antigens detected by anti-EP probably are B-cell-associated. The anti-EP intensely stained neoplastic cells of acute or chronic lymphocytic leukemia and lymphosarcoma-cell leukemia. Cells from two patients with chronic lymphocytic leukemia and from two patients with acute lymphocytic leukemia showed increased intensity of anti-EP staining and/or increased proportions of stained cells following overnight incubation in culture medium, compared with the preincubation samples. This observation suggests the presence of a \"blocking component(s)\" on cell surfaces, which interfered with anti-EP reactivity. After overnight incubation, the component might have been removed from the antigenic sites on cell surfaces. Further studies of leukemia lymphocytes using anti-EP for the cell-bound \"blocking component\" may reveal important pathogenetic mechanisms."}
{"id": "PMID:213967", "title": "Inhibition by propranolol of bile acid- and PGE1-stimulated camp and intestinal secretion.", "content": "Three colonic and three ileal loops were prepared in six rabbits pretreated with propranolol (PR) 4 mg./kg. I.V. and in five untreated rabbits. In random order, 1 ml. of either deoxycholic acid (DCA) 6 mM., prostaglandin E1 (PGE1) 20 microgram./ml., or saline was placed in each colonic loop and 1 ml. of either cholera enterotoxin (CE) 10 microgram./ml., PGE1 20 microgram./ml., or saline was placed in each ileal loop. In untreated animals, DCA and PGE1 in the colon and CE and PGE1 in the ileum stimulated (P less than 0.01) adenylate cyclase (AC) and net secretion. In the colon, PR abolished DCA-stimulation of AC and net secretion and decreased PGE1-stimulated AC (P less than 0.01) and net secretion. In conclusion, at the doses and times studied, colonic-AC and net secretion stimulated by PGE1 or DCA was distinguished from small bowel-AC and net secretion stimulated by PGE1 or CE.", "contents": "Inhibition by propranolol of bile acid- and PGE1-stimulated camp and intestinal secretion. Three colonic and three ileal loops were prepared in six rabbits pretreated with propranolol (PR) 4 mg./kg. I.V. and in five untreated rabbits. In random order, 1 ml. of either deoxycholic acid (DCA) 6 mM., prostaglandin E1 (PGE1) 20 microgram./ml., or saline was placed in each colonic loop and 1 ml. of either cholera enterotoxin (CE) 10 microgram./ml., PGE1 20 microgram./ml., or saline was placed in each ileal loop. In untreated animals, DCA and PGE1 in the colon and CE and PGE1 in the ileum stimulated (P less than 0.01) adenylate cyclase (AC) and net secretion. In the colon, PR abolished DCA-stimulation of AC and net secretion and decreased PGE1-stimulated AC (P less than 0.01) and net secretion. In conclusion, at the doses and times studied, colonic-AC and net secretion stimulated by PGE1 or DCA was distinguished from small bowel-AC and net secretion stimulated by PGE1 or CE."}
{"id": "PMID:213968", "title": "Cystosarcoma phyllodes metastatic to the pancreas.", "content": "A case is presented of cystosarcoma phyllodes of the breast metastatic to the pancreas. Solitary metastasis to the pancreas has not been reported. The lesion was excised in toto with a good result. Clinical and pathological features of cystosarcoma phyllodes are discussed.", "contents": "Cystosarcoma phyllodes metastatic to the pancreas. A case is presented of cystosarcoma phyllodes of the breast metastatic to the pancreas. Solitary metastasis to the pancreas has not been reported. The lesion was excised in toto with a good result. Clinical and pathological features of cystosarcoma phyllodes are discussed."}
{"id": "PMID:213973", "title": "Focal nodular hyperplasia of the liver and oral contraceptives.", "content": "The increased incidence of liver tumors in women of childbearing age who have been using oral contraceptives for many years suggests an environmental causation. The causative agent may be the steroidal oral contraceptives. Two lesions are recognized: focal nodular hyperplasia and hepatic adenoma. This paper concentrates on focal nodular hyperplasia, with two cases added to the four previously described cases. It is postulated that the estrogen component causes vascular lesions characterized by myointimal hyperplasia and thrombosis, leading to infarct, necrosis, and subsequent nodular hepatic regeneration. The clinical feature highlighted is the long history of gastrointestinal disturbance associated with negative gastrointestinal investigation with the possible exception of cholelithiasis. It is suggested that gray-scale ultrasonography is an effective screening method that also aids in a definitive diagnosis. As these tumors are often incidental findings it is emphasized that the liver should always be inspected at laparoscopy. Ultimately, diagnosis by biopsy or excision is essential as it may well be possible to treat cases of focal nodular hyperplasia of the liver conservatively, once oral contraceptives have been discontinued.", "contents": "Focal nodular hyperplasia of the liver and oral contraceptives. The increased incidence of liver tumors in women of childbearing age who have been using oral contraceptives for many years suggests an environmental causation. The causative agent may be the steroidal oral contraceptives. Two lesions are recognized: focal nodular hyperplasia and hepatic adenoma. This paper concentrates on focal nodular hyperplasia, with two cases added to the four previously described cases. It is postulated that the estrogen component causes vascular lesions characterized by myointimal hyperplasia and thrombosis, leading to infarct, necrosis, and subsequent nodular hepatic regeneration. The clinical feature highlighted is the long history of gastrointestinal disturbance associated with negative gastrointestinal investigation with the possible exception of cholelithiasis. It is suggested that gray-scale ultrasonography is an effective screening method that also aids in a definitive diagnosis. As these tumors are often incidental findings it is emphasized that the liver should always be inspected at laparoscopy. Ultimately, diagnosis by biopsy or excision is essential as it may well be possible to treat cases of focal nodular hyperplasia of the liver conservatively, once oral contraceptives have been discontinued."}
{"id": "PMID:213974", "title": "Cytomegalovirus in juvenile iridocyclitis.", "content": "We cultured cytomegalovirus from lens material aspirated from the eye of a 4-year-old boy who had a severe bilateral iridocyclitis and secondary cataracts. There were neither systemic manifestations of congenital disease nor chorioretinitis.", "contents": "Cytomegalovirus in juvenile iridocyclitis. We cultured cytomegalovirus from lens material aspirated from the eye of a 4-year-old boy who had a severe bilateral iridocyclitis and secondary cataracts. There were neither systemic manifestations of congenital disease nor chorioretinitis."}
{"id": "PMID:213975", "title": "Corneal donor material selection.", "content": "Histologic study of eyes used as donor material for corneal transplant revealed one instance of massive leukemic infiltration with leukemic keratic precipitates on the fellow eye. In another eye, microabscesses composed of acute and chronic inflammatory cells containing Crytococcus neoformans were present. In a third patient metastatic anaplastic cells were present in the choroid. We think donor eyes are absolutely unacceptable if death was caused by any chronic neurologic disorder, unless clearly secondary to trauma. Eyes from patients with septecimia, hepatitis, jaundice and any evidence of any active viral infection, syphilis, and positive serology are also unacceptable. Extreme caution should be used in selecting eyes of patients with ocular or systemic malignancy, long-term diseases, particularly if immunosuppressive agents were used, where a history of eye disease exists, including corneal disease or dystrophy, iritis, absolute glaucoma or acute glaucoma, and eyes with a history of previous intraocular surgery.", "contents": "Corneal donor material selection. Histologic study of eyes used as donor material for corneal transplant revealed one instance of massive leukemic infiltration with leukemic keratic precipitates on the fellow eye. In another eye, microabscesses composed of acute and chronic inflammatory cells containing Crytococcus neoformans were present. In a third patient metastatic anaplastic cells were present in the choroid. We think donor eyes are absolutely unacceptable if death was caused by any chronic neurologic disorder, unless clearly secondary to trauma. Eyes from patients with septecimia, hepatitis, jaundice and any evidence of any active viral infection, syphilis, and positive serology are also unacceptable. Extreme caution should be used in selecting eyes of patients with ocular or systemic malignancy, long-term diseases, particularly if immunosuppressive agents were used, where a history of eye disease exists, including corneal disease or dystrophy, iritis, absolute glaucoma or acute glaucoma, and eyes with a history of previous intraocular surgery."}
{"id": "PMID:213976", "title": "Acyclic antimetabolite therapy of experimental herpes simplex keratitis.", "content": "In a masked controlled study we compared 3% acycloguanosine, 0.5% idoxuridine, and 3% vidarabine ointments in therapy of experimental herpes simplex virus keratitis in rabbits. The results of the acycloguanosine group were significantly better than the control groups and both other treatment groups, while producing none of the toxic side effects of increasing iritis, conjunctivitis or stromal keratitis, with continued drug application.", "contents": "Acyclic antimetabolite therapy of experimental herpes simplex keratitis. In a masked controlled study we compared 3% acycloguanosine, 0.5% idoxuridine, and 3% vidarabine ointments in therapy of experimental herpes simplex virus keratitis in rabbits. The results of the acycloguanosine group were significantly better than the control groups and both other treatment groups, while producing none of the toxic side effects of increasing iritis, conjunctivitis or stromal keratitis, with continued drug application."}
{"id": "PMID:213977", "title": "Serum angiotensin converting enzyme activity and the capacity to develop hypertention-associated arterial disease. Studies during the induction phase of one-kidney perinephritis hypertension in rabbits.", "content": "Serum angiotensin converting enzyme (ACE) activity and plasma renin activity (PRA) were studied during the development of the widespread necrotic arterial disease that occurs in the induction phase of one-kidney perinephritis hypertension. Control serum ACE activity was significantly higher in rabbits developing many arterial lesions than it was in rabbits developing relatively few arterial lesions. Serum ACE decreased 7 days after the production of unilateral perinephritis in all rabbits. Following contralateral nephrectomy, serum ACE decreased further in rabbits devloping many arterial lesions but returned toward control values in rabbits developing relatively few arterial lesions. Significant inverse correlations were demonstrated for the total number of arterial lesions that developed relative to a) the decrease in serum ACE activity 7 days after the production of unilateral perinephritis, b) the lowest or the average serum ACE activity during the period of development of the arterial lesions after contralateral nephrectomy, and c) the change in serum ACE activity during the period of development of the arterial lesions. Chronic treatment with SQ 20,881, a synthetic nonapeptide inhibitor of ACE activity, during the period of development of the hypertension and the arterial lesions significantly reduced the serum ACE activity and the hypertension but did not change interrelationships between serum ACE activity and the number of arterial lesions that developed. PRA significantly decreased after the production of perinephritis and decreased somewhat further during the induction period of the hypertension after contralateral nephrectomy. No relationships were demonstrated between PRA, or changes in PRA, and the development of arterial lesions. The increase in blood pressure during the incubation period of the hypertension did not correlate with the number of arterial lesions that developed. These finding indicate that serum ACE activity reflects importantly on the capacity to develop necrotic arterial lesions during the induction phase of one-kidney perinephritis hypertention and on functional events relating to their pathogenesis.", "contents": "Serum angiotensin converting enzyme activity and the capacity to develop hypertention-associated arterial disease. Studies during the induction phase of one-kidney perinephritis hypertension in rabbits. Serum angiotensin converting enzyme (ACE) activity and plasma renin activity (PRA) were studied during the development of the widespread necrotic arterial disease that occurs in the induction phase of one-kidney perinephritis hypertension. Control serum ACE activity was significantly higher in rabbits developing many arterial lesions than it was in rabbits developing relatively few arterial lesions. Serum ACE decreased 7 days after the production of unilateral perinephritis in all rabbits. Following contralateral nephrectomy, serum ACE decreased further in rabbits devloping many arterial lesions but returned toward control values in rabbits developing relatively few arterial lesions. Significant inverse correlations were demonstrated for the total number of arterial lesions that developed relative to a) the decrease in serum ACE activity 7 days after the production of unilateral perinephritis, b) the lowest or the average serum ACE activity during the period of development of the arterial lesions after contralateral nephrectomy, and c) the change in serum ACE activity during the period of development of the arterial lesions. Chronic treatment with SQ 20,881, a synthetic nonapeptide inhibitor of ACE activity, during the period of development of the hypertension and the arterial lesions significantly reduced the serum ACE activity and the hypertension but did not change interrelationships between serum ACE activity and the number of arterial lesions that developed. PRA significantly decreased after the production of perinephritis and decreased somewhat further during the induction period of the hypertension after contralateral nephrectomy. No relationships were demonstrated between PRA, or changes in PRA, and the development of arterial lesions. The increase in blood pressure during the incubation period of the hypertension did not correlate with the number of arterial lesions that developed. These finding indicate that serum ACE activity reflects importantly on the capacity to develop necrotic arterial lesions during the induction phase of one-kidney perinephritis hypertention and on functional events relating to their pathogenesis."}
{"id": "PMID:213978", "title": "Pulmonary ultrastructure of the late aspects of human paraquat poisoning.", "content": "The pulmonary ultrastructure of the late aspects of a case of human paraquat poisoning is investigated and compared with normal human pulmonary ultrastructure. Alveoli in the paraquat patient are numerically reduced in comparison to the control. They are filled with edematous proteinaceous plasma-like fluid containing erythrocytes, macrophages, leukocytes, fibroblast-like cells, platelets, and fibrin. These alveoli are lined by granular pneumocytes. Interstitial areas in the paraquat patient are greatly expanded and there are no alveolar septums. Interstitial areas contain proteinaceous plasma-like material, collagen, fibrin, platelets, mature fibroblasts, plasma cells, many leukocytes, numerous erythrocytes, and capillaries. Capillary permeability seems to be enhanced in the paraquat patient either by vesicles forming transendothelial channels or pores or by disruption of endothelial cells.", "contents": "Pulmonary ultrastructure of the late aspects of human paraquat poisoning. The pulmonary ultrastructure of the late aspects of a case of human paraquat poisoning is investigated and compared with normal human pulmonary ultrastructure. Alveoli in the paraquat patient are numerically reduced in comparison to the control. They are filled with edematous proteinaceous plasma-like fluid containing erythrocytes, macrophages, leukocytes, fibroblast-like cells, platelets, and fibrin. These alveoli are lined by granular pneumocytes. Interstitial areas in the paraquat patient are greatly expanded and there are no alveolar septums. Interstitial areas contain proteinaceous plasma-like material, collagen, fibrin, platelets, mature fibroblasts, plasma cells, many leukocytes, numerous erythrocytes, and capillaries. Capillary permeability seems to be enhanced in the paraquat patient either by vesicles forming transendothelial channels or pores or by disruption of endothelial cells."}
{"id": "PMID:213979", "title": "Seasonal pattern in the rate of growth in height of children living in Guatemala.", "content": "Monthly increments of height for a sample of 164 Guatemala City school children are analyzed for the presence of a seasonal pattern in rates of growth. It is found that pre and post adolescent children follow a seasonal pattern of growth but adolescent children do not. It is suggested that the results are due to an effect of seasonal changes in ultraviolet light availability and the synthesis of vitamin D3 as mediated by the level of maturation of each child.", "contents": "Seasonal pattern in the rate of growth in height of children living in Guatemala. Monthly increments of height for a sample of 164 Guatemala City school children are analyzed for the presence of a seasonal pattern in rates of growth. It is found that pre and post adolescent children follow a seasonal pattern of growth but adolescent children do not. It is suggested that the results are due to an effect of seasonal changes in ultraviolet light availability and the synthesis of vitamin D3 as mediated by the level of maturation of each child."}
{"id": "PMID:213980", "title": "An evaluation of the miles method of ageing using the Tepe Hissar dental sample.", "content": "The Miles system of ageing, based upon analysis of the rate of molar wear, was evaluated using the available dental sample from Tepe Hissar, Iran. The independently estimated ages for the mandibles and maxillae of the same individuals were found to be highly correlated (r = 0.87, p less than 0.001). Ages of a subsample of the dentitions were compared with skeletal ages for the same individuals estimated from pubic symphyseal faces and found to be significantly correlated (r = 0.82, p less than 0.005) with no significant differences in the mean ages. Although a complete evaluation of the Miles method would require its testing on a controlled population, the available dental sample from Tepe Hissar provided evidence of the reliability and validity of the Miles method of ageing archeological populations on the basis of dental wear. Due to selective retention of burial remains, the available skeletal sample from Tepe Hissar I-III is not representative of the human populations of the site and can not be used to generate meaningful demographic statistics.", "contents": "An evaluation of the miles method of ageing using the Tepe Hissar dental sample. The Miles system of ageing, based upon analysis of the rate of molar wear, was evaluated using the available dental sample from Tepe Hissar, Iran. The independently estimated ages for the mandibles and maxillae of the same individuals were found to be highly correlated (r = 0.87, p less than 0.001). Ages of a subsample of the dentitions were compared with skeletal ages for the same individuals estimated from pubic symphyseal faces and found to be significantly correlated (r = 0.82, p less than 0.005) with no significant differences in the mean ages. Although a complete evaluation of the Miles method would require its testing on a controlled population, the available dental sample from Tepe Hissar provided evidence of the reliability and validity of the Miles method of ageing archeological populations on the basis of dental wear. Due to selective retention of burial remains, the available skeletal sample from Tepe Hissar I-III is not representative of the human populations of the site and can not be used to generate meaningful demographic statistics."}
{"id": "PMID:213981", "title": "Experimental amebiasis. III. A rapid in vitro assay for virulence of Entamoeba histolytica.", "content": "A rapid and simple assay for cytopathogenicity of axenically cultivated Entamoeba histolytica has been developed employing baby hamster kidney (BHK) or mouse 3T3 cells conventionally tissue cultured. Three of the twelve amebal strains tested produced total destruction of the BHK cell monolayer in 2--3 hours, and these three strains are the three most virulent strains for the newborn hamster liver. Two additional strains were of moderate cytopathogenicity in vitro and of moderate virulence in vivo. Seven strains were of low cytopathogenicity and virulence. Within these three major groupings, however, the cytopathogenicity ranking was not entirely reproducible. The general correspondence of cytopathogenicity in vitro and virulence in vivo and the possibility of obtaining data within a few hours suggest such an assay may prove a useful tool in amebiasis research.", "contents": "Experimental amebiasis. III. A rapid in vitro assay for virulence of Entamoeba histolytica. A rapid and simple assay for cytopathogenicity of axenically cultivated Entamoeba histolytica has been developed employing baby hamster kidney (BHK) or mouse 3T3 cells conventionally tissue cultured. Three of the twelve amebal strains tested produced total destruction of the BHK cell monolayer in 2--3 hours, and these three strains are the three most virulent strains for the newborn hamster liver. Two additional strains were of moderate cytopathogenicity in vitro and of moderate virulence in vivo. Seven strains were of low cytopathogenicity and virulence. Within these three major groupings, however, the cytopathogenicity ranking was not entirely reproducible. The general correspondence of cytopathogenicity in vitro and virulence in vivo and the possibility of obtaining data within a few hours suggest such an assay may prove a useful tool in amebiasis research."}
{"id": "PMID:213982", "title": "Hepatic amebiasis in spider monkeys.", "content": "In the past, investigators have been able to produce hepatic amebiasis in laboratory animals only by direct introduction of parasites into the liver or its vasculature, or by other artificial manipulations. A natural model of human visceral amebiasis has been lacking. We document an extensive outbreak of amebic dystentery which took place in a colony of spider monkeys; severe hepatic abscesses occurred in many animals. The spider monkey is highly susceptible to infection with Entamoeba histolytica and could provide a valuable model for the study of the pathogenesis of invasive amebiasis.", "contents": "Hepatic amebiasis in spider monkeys. In the past, investigators have been able to produce hepatic amebiasis in laboratory animals only by direct introduction of parasites into the liver or its vasculature, or by other artificial manipulations. A natural model of human visceral amebiasis has been lacking. We document an extensive outbreak of amebic dystentery which took place in a colony of spider monkeys; severe hepatic abscesses occurred in many animals. The spider monkey is highly susceptible to infection with Entamoeba histolytica and could provide a valuable model for the study of the pathogenesis of invasive amebiasis."}
{"id": "PMID:213983", "title": "The presence of liver auto-antibodies induced by Entamoeba histolytica in the sera from both naturally infected humans and immunized rabbits.", "content": "Auto-antibodies against normal human liver have been detected in the sera of humans with highly positive indirect hemagglutination (IHA) amebiasis titers and with clinically-proven amebic liver abscess. Sera of amebiasis patients and rabbits immunized with killed Entamoeba histolytica were tested for anti-amebic antibodies by the IHA test and for auto-antibodies by the complement fixation test, using the antigens prepared from extracts of human liver and rabbit liver. A direct correlation was found to exist between high anti-Entamoeba antibody titers and the presence of anti-liver antibody in the serum. It is proposed that, in addition to direct parasite damage to host tissue, immunological damage could result from the attachment of circulating antigen to the cell surfaces of host tissues such as the liver.", "contents": "The presence of liver auto-antibodies induced by Entamoeba histolytica in the sera from both naturally infected humans and immunized rabbits. Auto-antibodies against normal human liver have been detected in the sera of humans with highly positive indirect hemagglutination (IHA) amebiasis titers and with clinically-proven amebic liver abscess. Sera of amebiasis patients and rabbits immunized with killed Entamoeba histolytica were tested for anti-amebic antibodies by the IHA test and for auto-antibodies by the complement fixation test, using the antigens prepared from extracts of human liver and rabbit liver. A direct correlation was found to exist between high anti-Entamoeba antibody titers and the presence of anti-liver antibody in the serum. It is proposed that, in addition to direct parasite damage to host tissue, immunological damage could result from the attachment of circulating antigen to the cell surfaces of host tissues such as the liver."}
{"id": "PMID:213985", "title": "Granular cell tumor of the optic nerve.", "content": "A case of a combined neurofibroma-granular cell tumor is presented. The tumor had developed in the left middle cranial fossa after an intracranial trigeminal nerve operation 23 years before. It had displaced and infiltrated the temporal lobe and expanded probably via the fissura orbitalis into the orbit. The thickened optic nerve revealed a marked widening of the subdural fissure by typical granular cells. The cufflike tumor cell aggregation in the subdural fissure had compressed the optic fascicle, thereby inducing a demyelinisation and axonal degeneration. A reactive gliosis in the optic fascicle masks the typical pattern of the optic nerve atrophy. The gangliocytes of the third retinal neuron are atrophic and replaced by reactively proliferated fibrillary astrocytes. A short review of the literature and theories concerning histogenesis of the granular cell tumor (neurogenic or mesoderma) is given. An intermediary type of neurofibromatous and granular cells which we found motivates us to agree with a mesodermal origin.", "contents": "Granular cell tumor of the optic nerve. A case of a combined neurofibroma-granular cell tumor is presented. The tumor had developed in the left middle cranial fossa after an intracranial trigeminal nerve operation 23 years before. It had displaced and infiltrated the temporal lobe and expanded probably via the fissura orbitalis into the orbit. The thickened optic nerve revealed a marked widening of the subdural fissure by typical granular cells. The cufflike tumor cell aggregation in the subdural fissure had compressed the optic fascicle, thereby inducing a demyelinisation and axonal degeneration. A reactive gliosis in the optic fascicle masks the typical pattern of the optic nerve atrophy. The gangliocytes of the third retinal neuron are atrophic and replaced by reactively proliferated fibrillary astrocytes. A short review of the literature and theories concerning histogenesis of the granular cell tumor (neurogenic or mesoderma) is given. An intermediary type of neurofibromatous and granular cells which we found motivates us to agree with a mesodermal origin."}
{"id": "PMID:213986", "title": "Anaesthesia for carinal resection.", "content": "A case of adenocystic carcinoma (cylindroma) of the trachea is reported. Ventilation was successfully maintained for long periods by use of the venturi technique during resection of the carina, and during a later operation for relief of tracheal stenosis.", "contents": "Anaesthesia for carinal resection. A case of adenocystic carcinoma (cylindroma) of the trachea is reported. Ventilation was successfully maintained for long periods by use of the venturi technique during resection of the carina, and during a later operation for relief of tracheal stenosis."}
{"id": "PMID:213988", "title": "A histochemical study of the microvasculature in the left and right cardiac ventricles of the dog.", "content": "Subepicardial and subendocardial arteries and arterioles in both the left and right normal canine ventricle were examined histochemically to determine their metabolic profiles. Aerobic metabolic capacity was assessed by determining the reactivities of the enzymes cytochrome oxidase, succinate dehydrogenase and NAD-isocitrate dehydrogenase. Glucose-6-phosphate dehydrogenase was examined to assess activity of the hexose-monophosphate-shunt. The substrate glycogen was determined as an evaluation of anaerobic metabolic capacity, while the amounts of deoxyribonucleic and ribonucleic acid were assessed as an indication of protein synthesis. Results of the present investigation indicate that despite known hemodynamic differences, the metabolic profile of the coronary vasculature is similar in all regions of ventricular myocardium. Reactivities of the enzymes succinate and NAD-isocitrate dehydrogenase and cytochrome oxidase are greater in smooth muscle of arterioles than in arteries. This suggests that arteriolar smooth muscle has a higher capacity for aerobic metabolism than does arterial smooth muscle. The greater reactivity of glycogen in arterial, than in arteriolar smooth muscle, suggests that arterial muscle is more adapted for anaerobic metabolism. Deoxyribonucleic and ribonucleic acids demonstrate a low reactivity in both arteries and arterioles from all regions of ventricular myocardium which conforms to the opinion that under normal conditions, coronary vasculature is quite stable with little cell proliferation. Glucose-6-phosphate dehydrogenase shows little reactivity in all myocardial vessels with implies a low capacity for nucleic acid and protein synthesis.", "contents": "A histochemical study of the microvasculature in the left and right cardiac ventricles of the dog. Subepicardial and subendocardial arteries and arterioles in both the left and right normal canine ventricle were examined histochemically to determine their metabolic profiles. Aerobic metabolic capacity was assessed by determining the reactivities of the enzymes cytochrome oxidase, succinate dehydrogenase and NAD-isocitrate dehydrogenase. Glucose-6-phosphate dehydrogenase was examined to assess activity of the hexose-monophosphate-shunt. The substrate glycogen was determined as an evaluation of anaerobic metabolic capacity, while the amounts of deoxyribonucleic and ribonucleic acid were assessed as an indication of protein synthesis. Results of the present investigation indicate that despite known hemodynamic differences, the metabolic profile of the coronary vasculature is similar in all regions of ventricular myocardium. Reactivities of the enzymes succinate and NAD-isocitrate dehydrogenase and cytochrome oxidase are greater in smooth muscle of arterioles than in arteries. This suggests that arteriolar smooth muscle has a higher capacity for aerobic metabolism than does arterial smooth muscle. The greater reactivity of glycogen in arterial, than in arteriolar smooth muscle, suggests that arterial muscle is more adapted for anaerobic metabolism. Deoxyribonucleic and ribonucleic acids demonstrate a low reactivity in both arteries and arterioles from all regions of ventricular myocardium which conforms to the opinion that under normal conditions, coronary vasculature is quite stable with little cell proliferation. Glucose-6-phosphate dehydrogenase shows little reactivity in all myocardial vessels with implies a low capacity for nucleic acid and protein synthesis."}
{"id": "PMID:213990", "title": "Genetics of a low-density lipoprotein allotype in a cattle.", "content": "The paper describes a cattle serum antigen (LdlA1) located on a low-density lipoprotein and detected by single radial diffusion. The specificity is inherited in a simple Mendelian manner and the gene controlling its synthesis is inherited independently from the one controlling the synthesis of the alpha 2 macroglobulin McA1 antigen.", "contents": "Genetics of a low-density lipoprotein allotype in a cattle. The paper describes a cattle serum antigen (LdlA1) located on a low-density lipoprotein and detected by single radial diffusion. The specificity is inherited in a simple Mendelian manner and the gene controlling its synthesis is inherited independently from the one controlling the synthesis of the alpha 2 macroglobulin McA1 antigen."}
{"id": "PMID:213993", "title": "Intranasal tumor of the ethmoid olfactory mucosa in sheep.", "content": "Intranasal tumors (papillary adenomas or adenocarcinomas) of the ethmoid olfactory mucosa of sheep were investigated by light and electron microscopy. The fine structure of the tumor cells was characterized by the presence of numerous secretory granules. Viral particles, which were morphologically similar to a visna-maedi virus, were detected in all tumor tissues and in 3 of 4 cultures examined. The particles (about 97 nm) had an eccentrically located electron-dense core and numerous spikes on their surfaces. The RNA-dependent DNA polymerase activities in the tumor cells or the cultured cell from the tumor were greater than those in the normal intranasal tissues or the cultured cells from the choroid plexus. Viral particles similar to herpesvirus were also detected in 1 culture.", "contents": "Intranasal tumor of the ethmoid olfactory mucosa in sheep. Intranasal tumors (papillary adenomas or adenocarcinomas) of the ethmoid olfactory mucosa of sheep were investigated by light and electron microscopy. The fine structure of the tumor cells was characterized by the presence of numerous secretory granules. Viral particles, which were morphologically similar to a visna-maedi virus, were detected in all tumor tissues and in 3 of 4 cultures examined. The particles (about 97 nm) had an eccentrically located electron-dense core and numerous spikes on their surfaces. The RNA-dependent DNA polymerase activities in the tumor cells or the cultured cell from the tumor were greater than those in the normal intranasal tissues or the cultured cells from the choroid plexus. Viral particles similar to herpesvirus were also detected in 1 culture."}
{"id": "PMID:213989", "title": "Independence of gonadotropin and adrenal androgen secretion.", "content": "Five groups of 5 normal adult males have been studied. Group 1 received clomiphene, group 2 received exogenous FSH and group 3 testosterone. These three groups received drugs to stimulate LH and FSH, increase levels of FSH or suppress LH and FSH respectively. Circulating levels of testosterone (T), estrone (E1) and 17-hydroxyprogesterone (17-OHP) were altered while serum concentrations of androstenedione (A), dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DS) and urinary 17-ketosteroids (17-KS) were not. The other two groups of 5 adult males had adrenal androgen levels suppressed or stimulated while receiving dexamethasone or ACTH. Serum 17 OHP, A, DHA and DS levels and urinary 17 KS were affected while gonadotropins were unaltered. Hence, no relationship has been demonstrated between circulating levels of adrenal androgens and gonadotropins.", "contents": "Independence of gonadotropin and adrenal androgen secretion. Five groups of 5 normal adult males have been studied. Group 1 received clomiphene, group 2 received exogenous FSH and group 3 testosterone. These three groups received drugs to stimulate LH and FSH, increase levels of FSH or suppress LH and FSH respectively. Circulating levels of testosterone (T), estrone (E1) and 17-hydroxyprogesterone (17-OHP) were altered while serum concentrations of androstenedione (A), dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DS) and urinary 17-ketosteroids (17-KS) were not. The other two groups of 5 adult males had adrenal androgen levels suppressed or stimulated while receiving dexamethasone or ACTH. Serum 17 OHP, A, DHA and DS levels and urinary 17 KS were affected while gonadotropins were unaltered. Hence, no relationship has been demonstrated between circulating levels of adrenal androgens and gonadotropins."}
{"id": "PMID:213994", "title": "Preadsorption of boar semen with kaolin: increased efficiency of foot-and-mouth disease virus detection.", "content": "The boar semen-associated cytotoxic factor(s), but not the antiviral activity, were removed by adsorption with kaolin. Although foot-and-mouth disease virus was efficiently removed from medium by kaolin or kieselguhr, the virus was not removed from semen-virus mixtures. Because the cytotoxicity induced by boar semen apparently altered the ability of tissue culture cells to support virus replication, preadsorption with kaolin increased the probability of detecting this virus in semen samples.", "contents": "Preadsorption of boar semen with kaolin: increased efficiency of foot-and-mouth disease virus detection. The boar semen-associated cytotoxic factor(s), but not the antiviral activity, were removed by adsorption with kaolin. Although foot-and-mouth disease virus was efficiently removed from medium by kaolin or kieselguhr, the virus was not removed from semen-virus mixtures. Because the cytotoxicity induced by boar semen apparently altered the ability of tissue culture cells to support virus replication, preadsorption with kaolin increased the probability of detecting this virus in semen samples."}
{"id": "PMID:213996", "title": "Common membrane neoantigens on bovine papilloma virus-induced fibroma cells from cattle and horses.", "content": "Cultured cells from bovine papilloma virus (BPV)-induced fibroblastic tumors and normal dermis of cattle, horses, and hamsters were examined for cell membrane or internal neoantigens, using the indirect immunofluorescence technique. Sera from cattle and horses bearing BPV-induced fibromas cross reacted with cell membranes of tumor, but not with normal dermal cells of both species. The reaction could be blocked with homologous, but not heterologous, serum of these 2 species. Immunofluorescence was not detected with sera from hamsters bearing BPV-induced sarcomas if incubated with bovine, equine, or hamster cells. Internal neoantigens were not found in any of the acetone-fixed tumor cells, using sera from the 3 species. Both tumor and normal cells were all found free of BPV antigen, using direct immunofluorescence.", "contents": "Common membrane neoantigens on bovine papilloma virus-induced fibroma cells from cattle and horses. Cultured cells from bovine papilloma virus (BPV)-induced fibroblastic tumors and normal dermis of cattle, horses, and hamsters were examined for cell membrane or internal neoantigens, using the indirect immunofluorescence technique. Sera from cattle and horses bearing BPV-induced fibromas cross reacted with cell membranes of tumor, but not with normal dermal cells of both species. The reaction could be blocked with homologous, but not heterologous, serum of these 2 species. Immunofluorescence was not detected with sera from hamsters bearing BPV-induced sarcomas if incubated with bovine, equine, or hamster cells. Internal neoantigens were not found in any of the acetone-fixed tumor cells, using sera from the 3 species. Both tumor and normal cells were all found free of BPV antigen, using direct immunofluorescence."}
{"id": "PMID:213998", "title": "Cytomegalovirus infection in dialysis patients and personnel.", "content": "In a 12-month prospective study of cytomegalovirus infection on an acute hemodialysis unit, 10 of 80 patients (13%) and none of 26 staff developed active cytomegalovirus infection. Seven infections were coincidental with renal allograft rejection; three occurred 3 to 6 weeks after the transfusion of multiple units of conventional blood into seronegative patients. No person-to-person transmission was documented. In contrast to the effects of transfusing conventional blood, all 21 patients who entered dialysis without detectable cytomegalovirus antibody and received 2 to 10 U of frozen deglycerolyzed erythrocytes (total of 157 U) remained seronegative. Transmission of cytomegalovirus infection with transfusion with conventional blood is probably secondary to passage of leukocyte-borne virus that is lost during the freezing and deglycerolization procedure. Frozen erythrocytes prepared by cytoagglomeration procedures appear to be free of viable leukocytes and appear to carry a minimal risk of transmitting cytomegalovirus infection.", "contents": "Cytomegalovirus infection in dialysis patients and personnel. In a 12-month prospective study of cytomegalovirus infection on an acute hemodialysis unit, 10 of 80 patients (13%) and none of 26 staff developed active cytomegalovirus infection. Seven infections were coincidental with renal allograft rejection; three occurred 3 to 6 weeks after the transfusion of multiple units of conventional blood into seronegative patients. No person-to-person transmission was documented. In contrast to the effects of transfusing conventional blood, all 21 patients who entered dialysis without detectable cytomegalovirus antibody and received 2 to 10 U of frozen deglycerolyzed erythrocytes (total of 157 U) remained seronegative. Transmission of cytomegalovirus infection with transfusion with conventional blood is probably secondary to passage of leukocyte-borne virus that is lost during the freezing and deglycerolization procedure. Frozen erythrocytes prepared by cytoagglomeration procedures appear to be free of viable leukocytes and appear to carry a minimal risk of transmitting cytomegalovirus infection."}
{"id": "PMID:213999", "title": "Steroid hormone action: recent advances.", "content": "Pn entering the cell, steroid hormones are bound to specific cytoplasmic receptors. The hormone-receptor complexes are then translocated to the nucleus, in an \"activated\" form, whereupon they are bound to the target cell genome. The target cell responds by increased RNA synthesis with the transcription of specific mRNAs. The mRNAs are exported to the cytoplasm where protein synthesis takes place. Recent advances in steroid hormone action involve the purification of specific steroid hormone receptors and the preparation of specific antisera, the elucidation of the subunit structure of the progesterone receptor, the purification of a hormone-inducible mRNA and the synthesis of its DNA complement, the purification and amplification of the synthetic and natural gene for this RNA and the identification of intragenic spacers, and most recently the identification of specific precursors to the hormone-induced mRNA. We discuss here the medical significance of some of these advances.", "contents": "Steroid hormone action: recent advances. Pn entering the cell, steroid hormones are bound to specific cytoplasmic receptors. The hormone-receptor complexes are then translocated to the nucleus, in an \"activated\" form, whereupon they are bound to the target cell genome. The target cell responds by increased RNA synthesis with the transcription of specific mRNAs. The mRNAs are exported to the cytoplasm where protein synthesis takes place. Recent advances in steroid hormone action involve the purification of specific steroid hormone receptors and the preparation of specific antisera, the elucidation of the subunit structure of the progesterone receptor, the purification of a hormone-inducible mRNA and the synthesis of its DNA complement, the purification and amplification of the synthetic and natural gene for this RNA and the identification of intragenic spacers, and most recently the identification of specific precursors to the hormone-induced mRNA. We discuss here the medical significance of some of these advances."}
{"id": "PMID:214000", "title": "Plasma high-density lipoproteins and ischemic heart disease: studies in a large kindred with familial hypercholesterolemia.", "content": "The expression of ischemic heart disease was studied in a large kindred with familial hypercholesterolemia. Tendon xanthomas, multiple generation transmission, and the appearance of bimodality in the distributions of total and low-density lipoprotein cholesterol were found. The segregation ratio was 0.9 in females and 0.43 in males, a difference first apparent during adolescence. The upper quartile of total and low-density lipoprotein cholesterol contained all but two cases of ischemic disease, whereas the lower quartile of high-density lipoprotein cholesterol contained one half of the cases. The ratio of high- to low-density lipoprotein cholesterol (range, 0.06 to 1.6) was less than or equal to 0.20 in each patient with ischemic disease. The association of a low level of high-density lipoprotein cholesterol with ischemic disease persisted after adjustment for differences in other lipids and lipoproteins. A low level of high-density lipoprotein cholesterol, as well as a high level of low-density lipoprotein cholesterol, may influence the development of ischemic heart disease in this disorder.", "contents": "Plasma high-density lipoproteins and ischemic heart disease: studies in a large kindred with familial hypercholesterolemia. The expression of ischemic heart disease was studied in a large kindred with familial hypercholesterolemia. Tendon xanthomas, multiple generation transmission, and the appearance of bimodality in the distributions of total and low-density lipoprotein cholesterol were found. The segregation ratio was 0.9 in females and 0.43 in males, a difference first apparent during adolescence. The upper quartile of total and low-density lipoprotein cholesterol contained all but two cases of ischemic disease, whereas the lower quartile of high-density lipoprotein cholesterol contained one half of the cases. The ratio of high- to low-density lipoprotein cholesterol (range, 0.06 to 1.6) was less than or equal to 0.20 in each patient with ischemic disease. The association of a low level of high-density lipoprotein cholesterol with ischemic disease persisted after adjustment for differences in other lipids and lipoproteins. A low level of high-density lipoprotein cholesterol, as well as a high level of low-density lipoprotein cholesterol, may influence the development of ischemic heart disease in this disorder."}
{"id": "PMID:214002", "title": "[Coronavirus and \"astrovirus\" observed in stools of children with gastroenteritis (author's transl)].", "content": "In a year's survey (December 1976-November 1977) of 190 children admitted to hospital with acute gastroenteritis, an \"aetiological\" agent was found in stools by electron microscopy in 41% of cases. Rotavirus were found in 34% of patients. We also found Coronavirus-like particles and Astrovirus-like particles in 25 and 5 stools, respectively. Improvements are awaited to demonstrate the responsibility of these virus in gastroenteritis.", "contents": "[Coronavirus and \"astrovirus\" observed in stools of children with gastroenteritis (author's transl)]. In a year's survey (December 1976-November 1977) of 190 children admitted to hospital with acute gastroenteritis, an \"aetiological\" agent was found in stools by electron microscopy in 41% of cases. Rotavirus were found in 34% of patients. We also found Coronavirus-like particles and Astrovirus-like particles in 25 and 5 stools, respectively. Improvements are awaited to demonstrate the responsibility of these virus in gastroenteritis."}
{"id": "PMID:214003", "title": "Coinfection with a rhabdovirus: vesicular stomatitis virus of Indiana and New-Jersey serotypes.", "content": "Coinfection of cells with vesicular stomatitis virus (VSV) of Indiana and New-Jersey serotypes were performed. Thermosensitive mutants (ts) of VSV Indiana and the wild type strain (+) of New-Jersey were used. Harvests and titrations were made at permissive(PT) and nonpermissive (NPT) temperatures. It was shown that the harvest was mainly composed of one parental-like infectious particles. The dominance of one serotype over the other was shown to be a function of the relative multiplicity of the two viruses; the presence of a thermosensitive lesion imparts a disadvantage to the corresponding serotype. Non parental-like particles were also detected. As expected, these particles were detected only in two conditions. 1) Harvest performed at NPT and titrations allowed at PT.- Most of the infectious particles (i.e. twin particles) resistant to anti-Nj serum developped a plaque (i.e. mixed-plaque)containing virions of both serotypes: Indiana (ts) and New-Jersey (+). After sonication or EDTA treatment of the harvest, prior to titrations, no more mixed-plaques were formed. Examination of the harvest by electron microscopy showed that 7-17 % of the particles formed aggregates; therefore, it is likely that the twin-particles are in fact aggregates. 2) Harvest performed at PT and titrations allowed at NPT.-It has been shown that 1 % of the wild type infectious particles was resistant to anti-Nj serum even though being of Nj genotype. It was inactivated by a mixture of anti-Nj and anti-In sera and therfore behave as pseudotypes. But since twin particles, when plated at Nt, would give rise to an homogenous progeny from New-Jersey (+), they could be confused with pseudotypes. Under those conditions there is no absolute evidence that phenotypic mixing really occurs between VSV of Indiana and New-Jersey serotypes.", "contents": "Coinfection with a rhabdovirus: vesicular stomatitis virus of Indiana and New-Jersey serotypes. Coinfection of cells with vesicular stomatitis virus (VSV) of Indiana and New-Jersey serotypes were performed. Thermosensitive mutants (ts) of VSV Indiana and the wild type strain (+) of New-Jersey were used. Harvests and titrations were made at permissive(PT) and nonpermissive (NPT) temperatures. It was shown that the harvest was mainly composed of one parental-like infectious particles. The dominance of one serotype over the other was shown to be a function of the relative multiplicity of the two viruses; the presence of a thermosensitive lesion imparts a disadvantage to the corresponding serotype. Non parental-like particles were also detected. As expected, these particles were detected only in two conditions. 1) Harvest performed at NPT and titrations allowed at PT.- Most of the infectious particles (i.e. twin particles) resistant to anti-Nj serum developped a plaque (i.e. mixed-plaque)containing virions of both serotypes: Indiana (ts) and New-Jersey (+). After sonication or EDTA treatment of the harvest, prior to titrations, no more mixed-plaques were formed. Examination of the harvest by electron microscopy showed that 7-17 % of the particles formed aggregates; therefore, it is likely that the twin-particles are in fact aggregates. 2) Harvest performed at PT and titrations allowed at NPT.-It has been shown that 1 % of the wild type infectious particles was resistant to anti-Nj serum even though being of Nj genotype. It was inactivated by a mixture of anti-Nj and anti-In sera and therfore behave as pseudotypes. But since twin particles, when plated at Nt, would give rise to an homogenous progeny from New-Jersey (+), they could be confused with pseudotypes. Under those conditions there is no absolute evidence that phenotypic mixing really occurs between VSV of Indiana and New-Jersey serotypes."}
{"id": "PMID:214004", "title": "Stimulation of poly(adenosine diphosphate ribose) synthase activity of Xenopus germinal vesicle by progesterone.", "content": "A practical procedure for the isolation of massive numbers of GV from oocytes of Xenopus laevis at various stages of oogenesis was developed. The method is simple, rapid, and easy to perform. The isolated GV possess high activity of poly(ADP-ribose) synthase. Incubation of class-A oocytes (stages V and VI) with progesterone resulted in a stimulation of the poly(ADP-ribose) synthase activity in the GV. The stimulation of enzymatic activity occurred prior to GVBD. This stimulatory effect of progesterone on enzymatic activity was blocked by cycloheximide and actinomycin D, suggesting that induction is dependent on protein and RNA synthesis. Progesterone, however, was unable to cause disintegration of GV or to stimulate poly(ADP-ribose) synthase activity of class-B oocytes (stages III and IV). This finding suggests that the oocytes must progress to a certain stage of differentiation before progesterone can induce GVBD or stimulate poly(ADP-ribose) synthase activity.", "contents": "Stimulation of poly(adenosine diphosphate ribose) synthase activity of Xenopus germinal vesicle by progesterone. A practical procedure for the isolation of massive numbers of GV from oocytes of Xenopus laevis at various stages of oogenesis was developed. The method is simple, rapid, and easy to perform. The isolated GV possess high activity of poly(ADP-ribose) synthase. Incubation of class-A oocytes (stages V and VI) with progesterone resulted in a stimulation of the poly(ADP-ribose) synthase activity in the GV. The stimulation of enzymatic activity occurred prior to GVBD. This stimulatory effect of progesterone on enzymatic activity was blocked by cycloheximide and actinomycin D, suggesting that induction is dependent on protein and RNA synthesis. Progesterone, however, was unable to cause disintegration of GV or to stimulate poly(ADP-ribose) synthase activity of class-B oocytes (stages III and IV). This finding suggests that the oocytes must progress to a certain stage of differentiation before progesterone can induce GVBD or stimulate poly(ADP-ribose) synthase activity."}
{"id": "PMID:214005", "title": "Discussion paper: induction by progesterone and a \"maturation-promoting factor\" of soluble proteins in Xenopus laevis oocytes in vitro.", "content": "In vitro incubation of isolated X. laevis oocytes with progesterone induces the specific labeling of proteins during maturation. They are detected as several discrete peaks with a double-labeling technique that involves the injection of [3H] leucine into hormone-treated and [14C] leucine into control cells. The peaks are separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Identical proteins are obtained with two other steroids that provoke maturation and with p-chloromercuribenzoate. The same progesterone-induced proteins are observed even if oocytes have been treated with actinomycin D or ethidium bromide or have been enucleated. Cycloheximide suppresses the labeling of proteins that are induced by progesterone, if administered either at the time of radioactive amino acid exposure or after prelabeling the oocytes to determine whether the hormone-induced peaks are due to compartmental changes of the proteins. A cytoplasmic fraction, obtained from maturing oocytes before GVBD, promotes maturation when injected into resting oocytes and therefore contains an MPF. After this injection, GVBD occurs earlier than during incubation with progesterone and is accompanied by the formation of the same proteins and of MPF, both suppressed by cycloheximide. The possibility that MPF is an induced protein is then discussed. It has been also found that there is a decrease in membrane permeability, as evidenced by decreased leucine uptake into proteins of oocytes incubated in radioactive amino acids and exposed to progesterone. The same decrease occurs after injection of MPF-containing cytoplasm into oocytes.", "contents": "Discussion paper: induction by progesterone and a \"maturation-promoting factor\" of soluble proteins in Xenopus laevis oocytes in vitro. In vitro incubation of isolated X. laevis oocytes with progesterone induces the specific labeling of proteins during maturation. They are detected as several discrete peaks with a double-labeling technique that involves the injection of [3H] leucine into hormone-treated and [14C] leucine into control cells. The peaks are separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Identical proteins are obtained with two other steroids that provoke maturation and with p-chloromercuribenzoate. The same progesterone-induced proteins are observed even if oocytes have been treated with actinomycin D or ethidium bromide or have been enucleated. Cycloheximide suppresses the labeling of proteins that are induced by progesterone, if administered either at the time of radioactive amino acid exposure or after prelabeling the oocytes to determine whether the hormone-induced peaks are due to compartmental changes of the proteins. A cytoplasmic fraction, obtained from maturing oocytes before GVBD, promotes maturation when injected into resting oocytes and therefore contains an MPF. After this injection, GVBD occurs earlier than during incubation with progesterone and is accompanied by the formation of the same proteins and of MPF, both suppressed by cycloheximide. The possibility that MPF is an induced protein is then discussed. It has been also found that there is a decrease in membrane permeability, as evidenced by decreased leucine uptake into proteins of oocytes incubated in radioactive amino acids and exposed to progesterone. The same decrease occurs after injection of MPF-containing cytoplasm into oocytes."}
{"id": "PMID:214007", "title": "Glomus jugulare and vagale.", "content": "The therapeutic results in 72 patients with glomus jugulare and nine with glomus vagale have indicated a surgical cure rate of 80% in the former and 100% in the latter. Radiotherapy demonstrated a 65% tumor response rate and a 25% cure rate histologically and clinically. Embolization with Gelfoam beads in seven patients resulted in diminished tumor size and arterial circulation from the external carotid system. However, in all cases the tumor persisted. Embolization diminished intraoperative bleeding. Nevertheless, the use of embolization as a palliative modality demonstrated significant symptomatic relief in aged, debilitated patients and in all patients with large inoperable glomus jugulare tumors.", "contents": "Glomus jugulare and vagale. The therapeutic results in 72 patients with glomus jugulare and nine with glomus vagale have indicated a surgical cure rate of 80% in the former and 100% in the latter. Radiotherapy demonstrated a 65% tumor response rate and a 25% cure rate histologically and clinically. Embolization with Gelfoam beads in seven patients resulted in diminished tumor size and arterial circulation from the external carotid system. However, in all cases the tumor persisted. Embolization diminished intraoperative bleeding. Nevertheless, the use of embolization as a palliative modality demonstrated significant symptomatic relief in aged, debilitated patients and in all patients with large inoperable glomus jugulare tumors."}
{"id": "PMID:214008", "title": "Juvenile nasopharyngeal angiofibroma.", "content": "The diagnosis of angiofibroma can be suspected in most cases by clinical examination, supplemented by routine x-rays and tomograms and is confirmed by angiography. Adjunctive therapy including embolization, estrogens, cryotherapy and arterial ligation is discussed. Surgical resection is the preferred treatment. Radiotherapy as the primary treatment modality is contraindicated except in select cases.", "contents": "Juvenile nasopharyngeal angiofibroma. The diagnosis of angiofibroma can be suspected in most cases by clinical examination, supplemented by routine x-rays and tomograms and is confirmed by angiography. Adjunctive therapy including embolization, estrogens, cryotherapy and arterial ligation is discussed. Surgical resection is the preferred treatment. Radiotherapy as the primary treatment modality is contraindicated except in select cases."}
{"id": "PMID:214012", "title": "[Recent data on the group of melanotropic and lipotropic pituitary hormones (MSH-LPH) and on the brain morphinomimetic peptides (endorphins)].", "content": "It was admitted that human beta-MSH was responsible for the hyper-pigmentation observed in some syndromes associated with ACTH hypersecretion. beta-LPH was a pituitary polypeptide, containing the entire sequence of beta-MSH in its fragment 37-58, and the physiological role of which remained unknown. alpha-MSH and CLIP (Corticotrophin-like Intermediary Peptide) were thought to be specific of certain species possessing a distinct pituitary pars intermedia. Recent data give new insight upon some of these conceptions. beta-MSH seems not to exist in man; it is almost established now that plasma \"Immunoreactive beta-MSH\" (IR-beta-MSH) is in fact beta- and/or gamma-LPH. In chronic renal failure plasma IR-beta-MSH is elevated because of a decreased plasma disappearance rate, whereas ACTH is normal. Good evidence suggests that both LPH and ACTH are synthesized in the same pituitary cell within a common polypeptidic precursor. Endogenous peptides with morphinomimetic activity (Endorphins) have been isolated from brain and hypophysis; they are all made up of different fractions of beta-LPH-C-terminal fragment 61-91; It is likely that they represent a new class of brain neurotransmitters involved in some functions of the central nervous system, structural similarities suggest that beta-LPH may be the biosynthetic precursor of Endorphins, however such a hypothesis remains to be clearly demonstrated.", "contents": "[Recent data on the group of melanotropic and lipotropic pituitary hormones (MSH-LPH) and on the brain morphinomimetic peptides (endorphins)]. It was admitted that human beta-MSH was responsible for the hyper-pigmentation observed in some syndromes associated with ACTH hypersecretion. beta-LPH was a pituitary polypeptide, containing the entire sequence of beta-MSH in its fragment 37-58, and the physiological role of which remained unknown. alpha-MSH and CLIP (Corticotrophin-like Intermediary Peptide) were thought to be specific of certain species possessing a distinct pituitary pars intermedia. Recent data give new insight upon some of these conceptions. beta-MSH seems not to exist in man; it is almost established now that plasma \"Immunoreactive beta-MSH\" (IR-beta-MSH) is in fact beta- and/or gamma-LPH. In chronic renal failure plasma IR-beta-MSH is elevated because of a decreased plasma disappearance rate, whereas ACTH is normal. Good evidence suggests that both LPH and ACTH are synthesized in the same pituitary cell within a common polypeptidic precursor. Endogenous peptides with morphinomimetic activity (Endorphins) have been isolated from brain and hypophysis; they are all made up of different fractions of beta-LPH-C-terminal fragment 61-91; It is likely that they represent a new class of brain neurotransmitters involved in some functions of the central nervous system, structural similarities suggest that beta-LPH may be the biosynthetic precursor of Endorphins, however such a hypothesis remains to be clearly demonstrated."}
{"id": "PMID:214016", "title": "The EEG spike: signal of information transmission?", "content": "Enhanced neuronal excitability or coherence, leading to a rapid-bursting mode of unit discharge or to synchronous polarization, underlies the electroencephalographic spike. The propensity for EEG spike activity to occur in relation to events that require absolute command of neural circuitry suggests that the EEG spike represents a mode of discharge of underlying neural elements which is employed for communication of imperative messages. Normal when confined to certain axial nuclei of the brain during sleep or during photic or sexual excitation, compensatory in response to deafferentation or hypoxia, this powerful transmission mode must have certain advantages to have persisted throughout evolutionary history.", "contents": "The EEG spike: signal of information transmission? Enhanced neuronal excitability or coherence, leading to a rapid-bursting mode of unit discharge or to synchronous polarization, underlies the electroencephalographic spike. The propensity for EEG spike activity to occur in relation to events that require absolute command of neural circuitry suggests that the EEG spike represents a mode of discharge of underlying neural elements which is employed for communication of imperative messages. Normal when confined to certain axial nuclei of the brain during sleep or during photic or sexual excitation, compensatory in response to deafferentation or hypoxia, this powerful transmission mode must have certain advantages to have persisted throughout evolutionary history."}
{"id": "PMID:214017", "title": "A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release.", "content": "A new myasthenic syndrome is described in a patient whose symptoms began soon after birth and included generalized weakness increased by exertion, easy fatigability, hyporeflexia, and refractoriness to anticholinesterase drugs. Electromyography showed a decremental response at all frequencies of stimulation and a repetitive response to single nerve stimulation. Miniature end-plate potentials (mepps) were of normal amplitude but of decreased frequency. The mepp duration and half-decay time were prolonged, and prostigmine was without any addtitional effect. The quantum content of the end-plate potential was decreased due to a reduced store of quanta immediately available for release, but the probability of release was normal. Quantitative electron microscopy demonstrated a 3-fold to 4-fold decrease of nerve terminal size and reduced postsynaptic membrane density. The postsynaptic folds showed focal degeneration, and many were distended by labyrinthine membranous networks that communicated with the synaptic space. Degenerating nuclei were found in the junctional sarcoplasm. The ultrastructural localization of the acetylcholine receptor protein was normal. Acetylcholinesterase (AChE) was absent from the motor end-plates by histochemical and electron cytochemical criteria. Biochemical studies indicated total absence of the end-plate-specific 16 S species of AChE and marked decrease in total muscle AChE. A congenital defect in the molecular assembly of AChE or in its attachment to the postsynaptic membrane might represent the basic abnormality and condition the morphological and physiological alterations.", "contents": "A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release. A new myasthenic syndrome is described in a patient whose symptoms began soon after birth and included generalized weakness increased by exertion, easy fatigability, hyporeflexia, and refractoriness to anticholinesterase drugs. Electromyography showed a decremental response at all frequencies of stimulation and a repetitive response to single nerve stimulation. Miniature end-plate potentials (mepps) were of normal amplitude but of decreased frequency. The mepp duration and half-decay time were prolonged, and prostigmine was without any addtitional effect. The quantum content of the end-plate potential was decreased due to a reduced store of quanta immediately available for release, but the probability of release was normal. Quantitative electron microscopy demonstrated a 3-fold to 4-fold decrease of nerve terminal size and reduced postsynaptic membrane density. The postsynaptic folds showed focal degeneration, and many were distended by labyrinthine membranous networks that communicated with the synaptic space. Degenerating nuclei were found in the junctional sarcoplasm. The ultrastructural localization of the acetylcholine receptor protein was normal. Acetylcholinesterase (AChE) was absent from the motor end-plates by histochemical and electron cytochemical criteria. Biochemical studies indicated total absence of the end-plate-specific 16 S species of AChE and marked decrease in total muscle AChE. A congenital defect in the molecular assembly of AChE or in its attachment to the postsynaptic membrane might represent the basic abnormality and condition the morphological and physiological alterations."}
{"id": "PMID:214018", "title": "Giant axonal neuropathy: a childhood disorder of microfilaments.", "content": "A sural nerve biopsy was performed on an 8-year-old boy with a chronic, slowly progressive polyneuropathy. Light and electron microscopy as well as teased nerve-fiber preparations demonstrated numerous giant axons filled with closely packed neurofilaments. Both myelinated and unmyelinated fibers were involved. Segmental demyelination, remyelination, and onion-bulb formation by multiple Schwann cell processes were observed, suggesting recurrent Schwann cell dysfunction. Abundant aggregates of cytoplasmic microfilaments occurred in Schwann cells, endothelial cells, perineurial cells, endoneurial fibroblasts, and endomysial fibroblasts. These findings support the proposal that giant axonal neuropathy is a generalized disorder of cytoplasmic microfilaments and that segmental demyelination occurs concomitantly with axonal and Schwann cell disease. The pathogenesis of this rare disorder is discussed with reference to experimental toxic neuropathies.", "contents": "Giant axonal neuropathy: a childhood disorder of microfilaments. A sural nerve biopsy was performed on an 8-year-old boy with a chronic, slowly progressive polyneuropathy. Light and electron microscopy as well as teased nerve-fiber preparations demonstrated numerous giant axons filled with closely packed neurofilaments. Both myelinated and unmyelinated fibers were involved. Segmental demyelination, remyelination, and onion-bulb formation by multiple Schwann cell processes were observed, suggesting recurrent Schwann cell dysfunction. Abundant aggregates of cytoplasmic microfilaments occurred in Schwann cells, endothelial cells, perineurial cells, endoneurial fibroblasts, and endomysial fibroblasts. These findings support the proposal that giant axonal neuropathy is a generalized disorder of cytoplasmic microfilaments and that segmental demyelination occurs concomitantly with axonal and Schwann cell disease. The pathogenesis of this rare disorder is discussed with reference to experimental toxic neuropathies."}
{"id": "PMID:214019", "title": "Subacute measles encephalitis complicating Hodgkin's disease in an adult.", "content": "A progressive neurological illness characterized by myoclonus, motor and sensory deficits, and lethargy occurred in a patient with Hodgkin's disease and was fatal within two months. A focal inclusion cell encephalitis was demonstrated by immunohistological means to be due to measles virus. Measles encephalitis must be considered a potential opportunistic agent in the immune-compromised host.", "contents": "Subacute measles encephalitis complicating Hodgkin's disease in an adult. A progressive neurological illness characterized by myoclonus, motor and sensory deficits, and lethargy occurred in a patient with Hodgkin's disease and was fatal within two months. A focal inclusion cell encephalitis was demonstrated by immunohistological means to be due to measles virus. Measles encephalitis must be considered a potential opportunistic agent in the immune-compromised host."}
{"id": "PMID:214020", "title": "Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: use of virus-containing cells in the urine to assess response to therapy.", "content": "Two patients with biopsy-proved progressive multifocal leukoencephalopathy (PML) were treated with near-maximal doses of adenine arabinoside (Ara-A), 18.6 and 20 mg per kilogram of body weight per day for 14 days. In both patients, clinical progression of the disease was correlated with an increase in the size of low-density lesions seen by computerized tomography. One of the patients was observed to excrete abnormal epithelial cells into the urine. These cells contained papovaviruslike particles, and JC virus was cultured from the urine sediment. The relative number of these abnormal cells declined during Ara-A treatment. Both patients died shortly after the conclusion of therapy without a change in the progression of the central nervous system disease. Systemic administration of Ara-A did not offer significant clinical benefit in the treatment of these 2 advanced cases of PML.", "contents": "Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: use of virus-containing cells in the urine to assess response to therapy. Two patients with biopsy-proved progressive multifocal leukoencephalopathy (PML) were treated with near-maximal doses of adenine arabinoside (Ara-A), 18.6 and 20 mg per kilogram of body weight per day for 14 days. In both patients, clinical progression of the disease was correlated with an increase in the size of low-density lesions seen by computerized tomography. One of the patients was observed to excrete abnormal epithelial cells into the urine. These cells contained papovaviruslike particles, and JC virus was cultured from the urine sediment. The relative number of these abnormal cells declined during Ara-A treatment. Both patients died shortly after the conclusion of therapy without a change in the progression of the central nervous system disease. Systemic administration of Ara-A did not offer significant clinical benefit in the treatment of these 2 advanced cases of PML."}
{"id": "PMID:214021", "title": "Botulism: electrophysiological studies.", "content": "In a patient with botulism type B, electrophysiological studies showed: (1) a pattern in the repetitive nerve stimulation test resembling that found in the Eaton-Lambert syndrome but without any significant increment at high rates of stimulation or posttetanic exhaustion phenomenon; (2) a prominent response to guanidine hydrochloride; (3) a short mean duration of motor unit potentials that reversed with recovery; (4) a mild, prolonged latency and low amplitude of the H-reflex; (5) mild peripheral nerve dysfunction; and (6) a long-lasting persistence of abnormalities beyond the time of clinical recovery. The literature reports two types of responses in the repetitive nerve stimulation test in botulism: in the severe form one obtains a low-amplitude muscle potential, a decremental response at low rates of stimulation, and an insignificant incremental response at high rates of stimulation; in the mild form a normal amplitude of muscle potential occurs together with a normal response to low rates of stimulation and a significant incremental response at high rates of stimulation.", "contents": "Botulism: electrophysiological studies. In a patient with botulism type B, electrophysiological studies showed: (1) a pattern in the repetitive nerve stimulation test resembling that found in the Eaton-Lambert syndrome but without any significant increment at high rates of stimulation or posttetanic exhaustion phenomenon; (2) a prominent response to guanidine hydrochloride; (3) a short mean duration of motor unit potentials that reversed with recovery; (4) a mild, prolonged latency and low amplitude of the H-reflex; (5) mild peripheral nerve dysfunction; and (6) a long-lasting persistence of abnormalities beyond the time of clinical recovery. The literature reports two types of responses in the repetitive nerve stimulation test in botulism: in the severe form one obtains a low-amplitude muscle potential, a decremental response at low rates of stimulation, and an insignificant incremental response at high rates of stimulation; in the mild form a normal amplitude of muscle potential occurs together with a normal response to low rates of stimulation and a significant incremental response at high rates of stimulation."}
{"id": "PMID:214022", "title": "Huntington's chorea: selective depletion of activity of angiotensin coverting enzyme in the corpus striatum.", "content": "The activity of angiotensin converting enzyme, which transforms the relatively inactive decapeptide angiotensin I to the active octapeptide angiotensin II by removal of an L-histidyl-L-leucine residue, has been assayed in numerous region of the calf brain and of the brains of humans with Huntington's chorea and controls. In calf brain there are pronounced regional variations in enzyme activity, with highest activity in the globus pallidus and area postrema. In human brain, enzyme activity is highest in the corpus striatum, with similar levels in the caudate, putamen, and globus pallidus. Converting enzyme activity is reduced by 83 to 92% in the globus pallidus in Huntington's chorea. The caudate and putamen of choreic patients display 62 to 69% reductions in enzyme activity. Converting enzyme activity in two cerebral cortical regions from choreic brains is not significantly different from control.", "contents": "Huntington's chorea: selective depletion of activity of angiotensin coverting enzyme in the corpus striatum. The activity of angiotensin converting enzyme, which transforms the relatively inactive decapeptide angiotensin I to the active octapeptide angiotensin II by removal of an L-histidyl-L-leucine residue, has been assayed in numerous region of the calf brain and of the brains of humans with Huntington's chorea and controls. In calf brain there are pronounced regional variations in enzyme activity, with highest activity in the globus pallidus and area postrema. In human brain, enzyme activity is highest in the corpus striatum, with similar levels in the caudate, putamen, and globus pallidus. Converting enzyme activity is reduced by 83 to 92% in the globus pallidus in Huntington's chorea. The caudate and putamen of choreic patients display 62 to 69% reductions in enzyme activity. Converting enzyme activity in two cerebral cortical regions from choreic brains is not significantly different from control."}
{"id": "PMID:214023", "title": "Sequential cerebral biochemical and physiological events in controlled hypoxemia.", "content": "Effects of controlled hypoxemia on cerebral functional activity were studied in rats using cyclic adenosine monophosphate (cAMP) and aminergic neurotransmitters in the brain tissue as special references. Evidence is presented that: (1) mild hypoxemic stress (PaO2 60 to 40 torr) may activate cerebral glycolysis with no evidence of anaerobic metabolism but that further reduction of PaO2 impairs cellular respiration, as evidenced by accumulation of glycolytic products; (2) glycogenolysis in the brain tissue, leakage of potassium ions from the brain cell, increase in brain water, and suppression of neural functional activity occur concomitant with accumulation of cAMP and prior to the fall of adenosine triphosphate; (3) the diminution of cerebral high-energy phosphates during hypoxia is associated with and may be caused by hypoxemia-induced neuroglycopenia and occurs at PaO2 15 torr; (4) induced hypoxemia per se does not affect the level or aminergic neurotransmitter substances in brain tissue.", "contents": "Sequential cerebral biochemical and physiological events in controlled hypoxemia. Effects of controlled hypoxemia on cerebral functional activity were studied in rats using cyclic adenosine monophosphate (cAMP) and aminergic neurotransmitters in the brain tissue as special references. Evidence is presented that: (1) mild hypoxemic stress (PaO2 60 to 40 torr) may activate cerebral glycolysis with no evidence of anaerobic metabolism but that further reduction of PaO2 impairs cellular respiration, as evidenced by accumulation of glycolytic products; (2) glycogenolysis in the brain tissue, leakage of potassium ions from the brain cell, increase in brain water, and suppression of neural functional activity occur concomitant with accumulation of cAMP and prior to the fall of adenosine triphosphate; (3) the diminution of cerebral high-energy phosphates during hypoxia is associated with and may be caused by hypoxemia-induced neuroglycopenia and occurs at PaO2 15 torr; (4) induced hypoxemia per se does not affect the level or aminergic neurotransmitter substances in brain tissue."}
{"id": "PMID:214024", "title": "delta-Aminolevulinic acid: influences on synaptic GABA receptor binding may explain CNS symptoms of porphyria.", "content": "Symptoms of acute porphyria have been attributed to effects of delta-aminolevulinic acid (ALA). We report that ALA selectively competes for the binding of tritiated gamma-aminobutyric acid ([3H]GABA) associated with synaptic GABA receptors in central nervous system membranes. Concentrations of ALA that inhibit GABA receptor binding are consistent with levels of ALA thought to exist in the central nervous system of porphyric patients. Some of the symptoms of acute porphyria resemble those elicited by muscimol, a potent GABA agonist drug. Barbiturates, which exacerbate porphyric symptoms, are potent facilitators of the synaptic actions of GABA. The results suggest that some symptoms of acute porphyria might be attributable to a mimicking by ALA of GABA at its central nervous system receptor sites.", "contents": "delta-Aminolevulinic acid: influences on synaptic GABA receptor binding may explain CNS symptoms of porphyria. Symptoms of acute porphyria have been attributed to effects of delta-aminolevulinic acid (ALA). We report that ALA selectively competes for the binding of tritiated gamma-aminobutyric acid ([3H]GABA) associated with synaptic GABA receptors in central nervous system membranes. Concentrations of ALA that inhibit GABA receptor binding are consistent with levels of ALA thought to exist in the central nervous system of porphyric patients. Some of the symptoms of acute porphyria resemble those elicited by muscimol, a potent GABA agonist drug. Barbiturates, which exacerbate porphyric symptoms, are potent facilitators of the synaptic actions of GABA. The results suggest that some symptoms of acute porphyria might be attributable to a mimicking by ALA of GABA at its central nervous system receptor sites."}
{"id": "PMID:214025", "title": "The cerebrospinal fluid in visna, a slow viral disease of sheep.", "content": "The temporal development of the CSF abnormalities was examined in visna, a chronic neurological disease caused by a persistent viral infection of sheep. Two types of changes were observed. During the first 30 to 40 days there was an intense mononuclear pleocytosis associated with high protein and proportionately elevated IgG. Later, there was a persistent slight pleocytosis associated with mildly elevated protein which had an increased proportion of IgG and antivisna antibody. These later cellular and protein changes are similar to those found in a number of chronic neurological diseases of man.", "contents": "The cerebrospinal fluid in visna, a slow viral disease of sheep. The temporal development of the CSF abnormalities was examined in visna, a chronic neurological disease caused by a persistent viral infection of sheep. Two types of changes were observed. During the first 30 to 40 days there was an intense mononuclear pleocytosis associated with high protein and proportionately elevated IgG. Later, there was a persistent slight pleocytosis associated with mildly elevated protein which had an increased proportion of IgG and antivisna antibody. These later cellular and protein changes are similar to those found in a number of chronic neurological diseases of man."}
{"id": "PMID:214026", "title": "Mixed intracranial sarcomas: rare forms and a new association with previous radiation therapy.", "content": "The first two instances of mixed sarcoma-glioblastoma with a history of therapeutic irradiation to the head are reported, both occurring within one year of radiation therapy (for pituitary adenoma and residual meningioma). Two novel variants of mixed sarcomas of brain with extreme tumor metaplasia (fibromyxoosteochondrosarcoma and fibrochondroosteosarcoma-glioblastoma multiforme) are documented, and some of the problems concerning the origin of brain tumors with mixed population are discussed.", "contents": "Mixed intracranial sarcomas: rare forms and a new association with previous radiation therapy. The first two instances of mixed sarcoma-glioblastoma with a history of therapeutic irradiation to the head are reported, both occurring within one year of radiation therapy (for pituitary adenoma and residual meningioma). Two novel variants of mixed sarcomas of brain with extreme tumor metaplasia (fibromyxoosteochondrosarcoma and fibrochondroosteosarcoma-glioblastoma multiforme) are documented, and some of the problems concerning the origin of brain tumors with mixed population are discussed."}
{"id": "PMID:214027", "title": "[Antiviral action of carminomycin and some of its derivatives].", "content": "Carminomycin was shown to inhibit the development of both the DNA-containing variolovaccine virus and the RNA-containing grippe virus in chick embryos. Comparison of the effects of rubomycin, carminomycin, 14-oxy-carminomycin and carminomycin complex with bovine serum albumin in experiments with chick embryos showed that the inhibitory effect of carminomycin and its derivatives on the development of the grippe virus was much higher than that of rubomycin. The carminomycin derivatives proved to be much more active in this respect than the initial antibiotic. Carminomycin and its derivatives had a therapeutic effect on mice with experimental grippe pneumonia also on their oral use.", "contents": "[Antiviral action of carminomycin and some of its derivatives]. Carminomycin was shown to inhibit the development of both the DNA-containing variolovaccine virus and the RNA-containing grippe virus in chick embryos. Comparison of the effects of rubomycin, carminomycin, 14-oxy-carminomycin and carminomycin complex with bovine serum albumin in experiments with chick embryos showed that the inhibitory effect of carminomycin and its derivatives on the development of the grippe virus was much higher than that of rubomycin. The carminomycin derivatives proved to be much more active in this respect than the initial antibiotic. Carminomycin and its derivatives had a therapeutic effect on mice with experimental grippe pneumonia also on their oral use."}
{"id": "PMID:214028", "title": "Antiviral activity of intranasally applied human leukocyte interferon.", "content": "Previous studies in our laboratory have demonstrated that the development of antiviral activity of human leukocyte interferon (IF) in nasal epithelial cells is time and concentration dependent and that the loss of intranasally applied human leukocyte IF is rapid. The present studies compared the activity of IF applied intranasally either by nasal drops or by a saturated cotton pledget. Adult volunteers had IF applied to an area of nasal mucosa (2 by 2 cm(2)) either by repeated nose drops or by a saturated cotton pledget that was applied to the nasal mucosa and left in place for 1 h. Nasal epithelial cells scraped from the area of application, as well as the control, untreated side of the same volunteers, were challenged with vesicular stomatitis virus. No significant reduction in mean virus yield was found in volunteers who received 80,000 U by nose drops. Significant reduction (P < 0.025) in mean virus yield was found in cells obtained 4 h after 80,000, 50,000, or 20,000 U was applied by cotton pledget or in volunteers pretreated with oral antihistamines prior to receiving 80,000 U by nose drops. These experiments indicate that nasal epithelial cells can be made antiviral in vivo by application of human leukocyte IF. However, practical usefulness of human leukocyte IF for prophylaxis against respiratory viral infections may depend on the method of local application.", "contents": "Antiviral activity of intranasally applied human leukocyte interferon. Previous studies in our laboratory have demonstrated that the development of antiviral activity of human leukocyte interferon (IF) in nasal epithelial cells is time and concentration dependent and that the loss of intranasally applied human leukocyte IF is rapid. The present studies compared the activity of IF applied intranasally either by nasal drops or by a saturated cotton pledget. Adult volunteers had IF applied to an area of nasal mucosa (2 by 2 cm(2)) either by repeated nose drops or by a saturated cotton pledget that was applied to the nasal mucosa and left in place for 1 h. Nasal epithelial cells scraped from the area of application, as well as the control, untreated side of the same volunteers, were challenged with vesicular stomatitis virus. No significant reduction in mean virus yield was found in volunteers who received 80,000 U by nose drops. Significant reduction (P < 0.025) in mean virus yield was found in cells obtained 4 h after 80,000, 50,000, or 20,000 U was applied by cotton pledget or in volunteers pretreated with oral antihistamines prior to receiving 80,000 U by nose drops. These experiments indicate that nasal epithelial cells can be made antiviral in vivo by application of human leukocyte IF. However, practical usefulness of human leukocyte IF for prophylaxis against respiratory viral infections may depend on the method of local application."}
{"id": "PMID:214029", "title": "Generation of superoxide anions and hydrogen peroxide from beta-lapachone in bacteria.", "content": "beta-Lapachone markedly increased the generation of superoxide anions and hydrogen peroxide by subcellular membranes of Bacillus subtilis and Bacillus stearothermophilus. Peroxide generation by beta-lapachone was parallel to the inhibition of growth in both microorganisms.", "contents": "Generation of superoxide anions and hydrogen peroxide from beta-lapachone in bacteria. beta-Lapachone markedly increased the generation of superoxide anions and hydrogen peroxide by subcellular membranes of Bacillus subtilis and Bacillus stearothermophilus. Peroxide generation by beta-lapachone was parallel to the inhibition of growth in both microorganisms."}
{"id": "PMID:214030", "title": "Artifactual depression of serum glutamic oxaloacetic transaminase by metronidazole.", "content": "Eighteen patients developed abnormally low serum glutamic oxaloacetic transaminase values during metronidazole therapy. Metronidazole absorbs at 340 nm, simulating reduced nicotinamide adenine dinucleotide, which is the final colorimetric product of the serum glutamic oxaloacetic transaminase assay.", "contents": "Artifactual depression of serum glutamic oxaloacetic transaminase by metronidazole. Eighteen patients developed abnormally low serum glutamic oxaloacetic transaminase values during metronidazole therapy. Metronidazole absorbs at 340 nm, simulating reduced nicotinamide adenine dinucleotide, which is the final colorimetric product of the serum glutamic oxaloacetic transaminase assay."}
{"id": "PMID:214042", "title": "Progressive nodular histiocytoma.", "content": "Extensive evaluation of the condition of a 9-year-old girl with a previously undescribed proliferative histocytic syndrome showed normal serum and tissue lipid values, which rule out the known lipid storage diseases. Clinically and histologically the case is inconsistent with any of the recognized xanthomatoses or histiocytic abnormalities.", "contents": "Progressive nodular histiocytoma. Extensive evaluation of the condition of a 9-year-old girl with a previously undescribed proliferative histocytic syndrome showed normal serum and tissue lipid values, which rule out the known lipid storage diseases. Clinically and histologically the case is inconsistent with any of the recognized xanthomatoses or histiocytic abnormalities."}
{"id": "PMID:214043", "title": "Malignant neoplasms of the paranasal sinuses involving the skin.", "content": "Malignant neoplasms of the mucosa and minor salivary glands of the paranasal sinuses may involve the skin by direct extension. When a tumor appears on the overlying skin, these sinuses should be considered as a possible site of origin. Adenoid cystic carcinoma of the paranasal sinuses arise from minor salivary glands. They can infiltrate overlying skin and easily be confused with a primary cutaneous adenoid cystic carcinoma. Malignant melanomas of the paranasal sinuses are clinically very aggressive. They are often amelanotic, and this may lead to an incorrect histopathologic diagnosis. Hence, physical and radiological examination of the nose, mouth, and paranasal sinuses should be performed whenever a tumor appears in the overlying skin that does not have a clear cutaneous origin or whenever the primary site of a metastatic malignant melanoma is unknown.", "contents": "Malignant neoplasms of the paranasal sinuses involving the skin. Malignant neoplasms of the mucosa and minor salivary glands of the paranasal sinuses may involve the skin by direct extension. When a tumor appears on the overlying skin, these sinuses should be considered as a possible site of origin. Adenoid cystic carcinoma of the paranasal sinuses arise from minor salivary glands. They can infiltrate overlying skin and easily be confused with a primary cutaneous adenoid cystic carcinoma. Malignant melanomas of the paranasal sinuses are clinically very aggressive. They are often amelanotic, and this may lead to an incorrect histopathologic diagnosis. Hence, physical and radiological examination of the nose, mouth, and paranasal sinuses should be performed whenever a tumor appears in the overlying skin that does not have a clear cutaneous origin or whenever the primary site of a metastatic malignant melanoma is unknown."}
{"id": "PMID:214045", "title": "[The lymphocyte transformation test in patients with recurrent herpes simplex diseases (author's transl)].", "content": "The in vivo stimulation of lymphocytes was used to assess cell mediated immunity to herpes simplex virus (hsv) in patients with recurrent skin eruptions caused by this virus. 1. Phytohaemagglutinine stimulation of lymphocytes was normal in all examined patients. There was no difference in the PHA-stimulation of a control group. 2. Specific lymphocytes stimulation by hsv-antigen may be regarded as a sensitive parameter for a previous hsv-infection. 3. In 6 patients with severe infections of hsv type I or II and more than 10 recurrences per year we found a lower stimulation than in patients with occasionally (up to 10 times a year) skin eruptions. 4. An antigen used as vaccine, Lupidon H, ten times more concentrated (100,000 EID/ml) than the commercially available antigen is able to stimulate lymphocytes in vitro.", "contents": "[The lymphocyte transformation test in patients with recurrent herpes simplex diseases (author's transl)]. The in vivo stimulation of lymphocytes was used to assess cell mediated immunity to herpes simplex virus (hsv) in patients with recurrent skin eruptions caused by this virus. 1. Phytohaemagglutinine stimulation of lymphocytes was normal in all examined patients. There was no difference in the PHA-stimulation of a control group. 2. Specific lymphocytes stimulation by hsv-antigen may be regarded as a sensitive parameter for a previous hsv-infection. 3. In 6 patients with severe infections of hsv type I or II and more than 10 recurrences per year we found a lower stimulation than in patients with occasionally (up to 10 times a year) skin eruptions. 4. An antigen used as vaccine, Lupidon H, ten times more concentrated (100,000 EID/ml) than the commercially available antigen is able to stimulate lymphocytes in vitro."}
{"id": "PMID:214046", "title": "Presence of two typical DNA-binding nonhistone proteins in psoriatic scales contrary to normal human dermis, epidermis and horny layer.", "content": "The composition of DNA-binding proteins (DBP) was shown to be tissue-specific and to vary at different stages of gene expression. As the accelerated epidermopoesis in psoriasis indicates changed gene activities, DBP of psoriatic scales were compared with those of normal human epidermis, dermis and horny layer. Each skin fraction is characterized by its own DBP pattern, indicating different cell species. 1. The DBP of normal human epidermis shows only a small accordance with the DBP of human dermis and implies their difference in origin, function and cell types. 2. Psoriatic scale DBP and epidermal DPB contain more corresponding proteins which can be deduced from the scale's origin from epidermis. However, the composition of all proteins differs to a great extent. This either occurred during parakeratotic keratinization or reflects differences of normal to psoriatic epidermis. Imposing for psoriatic scale DBP are two protein bands with molecular weights of 84,000 and 90,000 daltons. Evidently both are not present in the DBP of other skin layers. 3. The horny layer contains a very small amount of DBP which might represent DNases to a major part. The small DBP content in horny layer confirms the previous supposition of psoriatic scales, to be mostly derived from the preserved nuclei of the parakeratotic scale layer.", "contents": "Presence of two typical DNA-binding nonhistone proteins in psoriatic scales contrary to normal human dermis, epidermis and horny layer. The composition of DNA-binding proteins (DBP) was shown to be tissue-specific and to vary at different stages of gene expression. As the accelerated epidermopoesis in psoriasis indicates changed gene activities, DBP of psoriatic scales were compared with those of normal human epidermis, dermis and horny layer. Each skin fraction is characterized by its own DBP pattern, indicating different cell species. 1. The DBP of normal human epidermis shows only a small accordance with the DBP of human dermis and implies their difference in origin, function and cell types. 2. Psoriatic scale DBP and epidermal DPB contain more corresponding proteins which can be deduced from the scale's origin from epidermis. However, the composition of all proteins differs to a great extent. This either occurred during parakeratotic keratinization or reflects differences of normal to psoriatic epidermis. Imposing for psoriatic scale DBP are two protein bands with molecular weights of 84,000 and 90,000 daltons. Evidently both are not present in the DBP of other skin layers. 3. The horny layer contains a very small amount of DBP which might represent DNases to a major part. The small DBP content in horny layer confirms the previous supposition of psoriatic scales, to be mostly derived from the preserved nuclei of the parakeratotic scale layer."}
{"id": "PMID:214047", "title": "A longitudinal study of in vitro tests for lymphocyte function in rheumatoid arthritis.", "content": "In vitro tests of lymphocyte function have been performed in 61 patients with ;classical' or ;definite' rheumatoid arthritis. In vitro lymphocyte function was assessed by lymphocyte transformation responses to phytohaemagglutinin (PHA), Pokeweed mitogen (PWM), Candida antigen, and herpes simplex type I (HSV1). Follow up data were available after 6 months of treatment in 32 of these patients. Spontaneous lymphocyte transformation was assessed in all patients. Results obtained in patients with rheumatoid arthiritis were compared to those seen in a normal control population. Disease activity of patients with rheumatoid arthritis was assessed using standard clinical methods. Lymphocytes from patients with rheumatoid arthritis showed a similar degree of spontaneous transformation to that seen in normal subjects. In contrast, lymphocytes from patients with rheumatoid arthritis responded less well to PHA and Candida and HSV1 antigens when compared to normal patients. In patients with rheumatoid arthritis the response to PWM was markedly enhanced compared to normals. Clinical improvement was noted in 19 of the 32 patients seen at follow up, all of whom had received gold or penicillamine therapy. The abnormal responses of PHA and PWM seen before treatment became normal in those patients who improved clinically. The responses to Candida and HSV1 antigens not only returned to normal following treatment but were increased above those seen in normal controls. A statistically significant association was seen between clinical improvement and improvement of in vitro tests of lymphocyte function.", "contents": "A longitudinal study of in vitro tests for lymphocyte function in rheumatoid arthritis. In vitro tests of lymphocyte function have been performed in 61 patients with ;classical' or ;definite' rheumatoid arthritis. In vitro lymphocyte function was assessed by lymphocyte transformation responses to phytohaemagglutinin (PHA), Pokeweed mitogen (PWM), Candida antigen, and herpes simplex type I (HSV1). Follow up data were available after 6 months of treatment in 32 of these patients. Spontaneous lymphocyte transformation was assessed in all patients. Results obtained in patients with rheumatoid arthiritis were compared to those seen in a normal control population. Disease activity of patients with rheumatoid arthritis was assessed using standard clinical methods. Lymphocytes from patients with rheumatoid arthritis showed a similar degree of spontaneous transformation to that seen in normal subjects. In contrast, lymphocytes from patients with rheumatoid arthritis responded less well to PHA and Candida and HSV1 antigens when compared to normal patients. In patients with rheumatoid arthritis the response to PWM was markedly enhanced compared to normals. Clinical improvement was noted in 19 of the 32 patients seen at follow up, all of whom had received gold or penicillamine therapy. The abnormal responses of PHA and PWM seen before treatment became normal in those patients who improved clinically. The responses to Candida and HSV1 antigens not only returned to normal following treatment but were increased above those seen in normal controls. A statistically significant association was seen between clinical improvement and improvement of in vitro tests of lymphocyte function."}
{"id": "PMID:214048", "title": "Lactic acidosis in oat cell carcinoma with extensive hepatic metastases.", "content": "Lactic acidosis has been described in patients with leukemia and lymphoma, but its occurrence in other malignant diseases is not documented. We treated two patients with oat cell carcinoma of the lung and extensive liver metastases in whom lactic acidosis developed. Tumor-induced hepatic dysfunction appeared to be a major factor in the pathogenesis of the lactic acidosis observed in these patients.", "contents": "Lactic acidosis in oat cell carcinoma with extensive hepatic metastases. Lactic acidosis has been described in patients with leukemia and lymphoma, but its occurrence in other malignant diseases is not documented. We treated two patients with oat cell carcinoma of the lung and extensive liver metastases in whom lactic acidosis developed. Tumor-induced hepatic dysfunction appeared to be a major factor in the pathogenesis of the lactic acidosis observed in these patients."}
{"id": "PMID:214049", "title": "Superoxide dismutase and hydrogen peroxide formation in Campylobacter sputorum subspecies bubulus.", "content": "Cell-free extracts of Campylobacter sputorum subspecies bubulus contained superoxide dismutase. The enzyme was located in the cytoplasmic fraction and insensitive to cyanide. After centrifuging a cell-free extract at 144000 x g for 1.5 h the total activity in the supernatant fraction was threefold higher than in the crude cell-free extract. The pellet fraction thus obtained was shown to have a lowering effect on superoxide dismutase activities from different sources in the assay method used here. C. sputorum responded to a raised oxygen tension in the culture by an increase in the superoxide dismutase activity. The ability to produce superoxide anion radicals (O2-.) during oxidation of formate and lactate was demonstrated. Furthermore C. sputorum was found to produce H2O2 while oxidizing formate. In experiments in which the reduction of cytochrome c by formate was followed, step-wise kinetics were observed. One of the steady states then obtained was attributed to the oxidizing action of H2O2, because it was abolished by the addition of catalase and lengthened by H2O2 added in addition to H2O2 formed as a product of formate oxidation. An overall reaction for formate oxidation by C. sputorum is discussed.", "contents": "Superoxide dismutase and hydrogen peroxide formation in Campylobacter sputorum subspecies bubulus. Cell-free extracts of Campylobacter sputorum subspecies bubulus contained superoxide dismutase. The enzyme was located in the cytoplasmic fraction and insensitive to cyanide. After centrifuging a cell-free extract at 144000 x g for 1.5 h the total activity in the supernatant fraction was threefold higher than in the crude cell-free extract. The pellet fraction thus obtained was shown to have a lowering effect on superoxide dismutase activities from different sources in the assay method used here. C. sputorum responded to a raised oxygen tension in the culture by an increase in the superoxide dismutase activity. The ability to produce superoxide anion radicals (O2-.) during oxidation of formate and lactate was demonstrated. Furthermore C. sputorum was found to produce H2O2 while oxidizing formate. In experiments in which the reduction of cytochrome c by formate was followed, step-wise kinetics were observed. One of the steady states then obtained was attributed to the oxidizing action of H2O2, because it was abolished by the addition of catalase and lengthened by H2O2 added in addition to H2O2 formed as a product of formate oxidation. An overall reaction for formate oxidation by C. sputorum is discussed."}
{"id": "PMID:214050", "title": "Fumarate reductase of Clostridium formicoaceticum. A peripheral membrane protein.", "content": "When Clostridium formicoaceticum was grown on fumarate or L-malate crude cell extracts contained a high fumarate reductase activity. Using reduced methyl viologen as electron donor the specific activity amounted to 2-3.5 U per mg of protein. Reduced benzyl viologen, FMNH2 and NADH could also serve as electron donors but the specific activities were much lower. The NADH-dependent activity was strictly membrane-bound and rather labile. Its specific activity did not exceed 0.08 U per mg of particle protein. Fumarate reductase activity was also found in cells of C. formicoaceticum grown on fructose, gluconate, glutamate and some other substrates. The methyl viologen-dependent fumarate reductase activity could almost completely be measured with intact cells whereas only about 25% of the cytoplasmic acetate kinase activity was detected with cell suspensions. The preparation of spheroplasts from cells of C. formicoaceticum in 20 mM HEPES-KOH buffer containing 0.6 M sucrose and 1 mM dithioerythritol resulted in the specific release of 88% of the fumarate reductase activity into the spheroplast medium. Only small amounts of the cytoplasmic proteins malic enzyme and acetate kinase were released during this procedure. There results indicate a peripheral location of the fumarate reductase of C. formicoaceticum on the membrane.", "contents": "Fumarate reductase of Clostridium formicoaceticum. A peripheral membrane protein. When Clostridium formicoaceticum was grown on fumarate or L-malate crude cell extracts contained a high fumarate reductase activity. Using reduced methyl viologen as electron donor the specific activity amounted to 2-3.5 U per mg of protein. Reduced benzyl viologen, FMNH2 and NADH could also serve as electron donors but the specific activities were much lower. The NADH-dependent activity was strictly membrane-bound and rather labile. Its specific activity did not exceed 0.08 U per mg of particle protein. Fumarate reductase activity was also found in cells of C. formicoaceticum grown on fructose, gluconate, glutamate and some other substrates. The methyl viologen-dependent fumarate reductase activity could almost completely be measured with intact cells whereas only about 25% of the cytoplasmic acetate kinase activity was detected with cell suspensions. The preparation of spheroplasts from cells of C. formicoaceticum in 20 mM HEPES-KOH buffer containing 0.6 M sucrose and 1 mM dithioerythritol resulted in the specific release of 88% of the fumarate reductase activity into the spheroplast medium. Only small amounts of the cytoplasmic proteins malic enzyme and acetate kinase were released during this procedure. There results indicate a peripheral location of the fumarate reductase of C. formicoaceticum on the membrane."}
{"id": "PMID:214051", "title": "Effect of guanosine 5'-diphosphate 3'-diphosphate and related nucleoside polyphosphates on induction of tryptophanase and beta-galactosidase in permeabilized cells of Escherichia coli.", "content": "Exogenous addition of guanosine and adenosine 5'-(mono, di and tri) phosphate 3'-diphosphates (pppGpp, ppGpp, pGpp, pppApp, ppApp and pApp) stimulated the synthesis of tryptophanase and beta-galactosidase in permeabilized cells of Escherichia coli. From the results obtained with ppGpp and pppApp, this effect appeared to be at a transcriptional level and depended greatly on the growth condition; the largest effect was observed in cells under shiftdown or grown on poor enrgy source. ppGpp and pppApp, unlike cyclic AMP, did not act to overcome the inhibition of enzyme induction by glucose, but in combination with cyclic AMP caused a synergistic stimulation effect. In the shiftdown cells, ppGpp and pppApp gave 30% or more stimulation effect on tryptophanase induction while cyclic AMP did not stimulate induction. There was therefore a pronounced difference between cyclic AMP and ppGpp or pppApp in stimulatory function.", "contents": "Effect of guanosine 5'-diphosphate 3'-diphosphate and related nucleoside polyphosphates on induction of tryptophanase and beta-galactosidase in permeabilized cells of Escherichia coli. Exogenous addition of guanosine and adenosine 5'-(mono, di and tri) phosphate 3'-diphosphates (pppGpp, ppGpp, pGpp, pppApp, ppApp and pApp) stimulated the synthesis of tryptophanase and beta-galactosidase in permeabilized cells of Escherichia coli. From the results obtained with ppGpp and pppApp, this effect appeared to be at a transcriptional level and depended greatly on the growth condition; the largest effect was observed in cells under shiftdown or grown on poor enrgy source. ppGpp and pppApp, unlike cyclic AMP, did not act to overcome the inhibition of enzyme induction by glucose, but in combination with cyclic AMP caused a synergistic stimulation effect. In the shiftdown cells, ppGpp and pppApp gave 30% or more stimulation effect on tryptophanase induction while cyclic AMP did not stimulate induction. There was therefore a pronounced difference between cyclic AMP and ppGpp or pppApp in stimulatory function."}
{"id": "PMID:214052", "title": "Fine structure of the dome in Peyer's patches of mice.", "content": "The dome area of Peyer's patches in adult mice was studied by electron microscopy. The cellular constituents of the area are lymphocytes, plasma cells, macrophages and reticular cells. Macrophages are filled with numerous lysosomal bodies containing dead lymphocytes or plasma cells. The epithelium covering the dome is infiltrated with numerous lymphocytes, a few plasma cells and macrophages. These wandering cells first are found intercellularly but later appear to penetrate into the epithelial cell cytoplasm just beneath the cell apex. The epithelial cells containing the wandering cells in the supranuclear portion protrude into the intestinal lumen, and their microvilli are short and scanty. The epithelial cells covering the dome often have inclusion bodies containing dead wandering cells. Such modification of the epithelial cells may be related to the presence of underlying follicles. The results suggest that the dome including the covering epithelium is a site in which antigens from the intestinal lumen might come in direct contact with lymphocytes or other wandering cells.", "contents": "Fine structure of the dome in Peyer's patches of mice. The dome area of Peyer's patches in adult mice was studied by electron microscopy. The cellular constituents of the area are lymphocytes, plasma cells, macrophages and reticular cells. Macrophages are filled with numerous lysosomal bodies containing dead lymphocytes or plasma cells. The epithelium covering the dome is infiltrated with numerous lymphocytes, a few plasma cells and macrophages. These wandering cells first are found intercellularly but later appear to penetrate into the epithelial cell cytoplasm just beneath the cell apex. The epithelial cells containing the wandering cells in the supranuclear portion protrude into the intestinal lumen, and their microvilli are short and scanty. The epithelial cells covering the dome often have inclusion bodies containing dead wandering cells. Such modification of the epithelial cells may be related to the presence of underlying follicles. The results suggest that the dome including the covering epithelium is a site in which antigens from the intestinal lumen might come in direct contact with lymphocytes or other wandering cells."}
{"id": "PMID:214053", "title": "Corticotropin stimulation of hypertensive rats with and without arteriosclerosis.", "content": "Male and female, nonarteriosclerotic (virgin) and arteriosclerotic (breeder), Sprague-Dawley rats were subjected to the hypertension-producing regimen of uninephrectomy, 1% saline drinking water, and desoxycorticosterone (Percorten) pivalate. Just before autopsy, some of the animals were given a single injection of corticotropin. The acute challenge of corticotropin caused a definite increase in free fatty acids, systolic blood pressure, creatine phosphokinase, glucose, and corticosterone. The two weeks of desoxycorticosterone and 1% saline-induced hypertension caused myocarditis and hyalinization of the coronary arteries of the nonarteriosclerotic (virgin) rats and definite exacerbation of the preexisting arteriosclerosis in breeder rats, severe myocarditis, and polyarteritis nodosa. All of the treated animals manifested lipid depletion of the zona glomerulosa indicative of reduced biosynthesis and secretion of endogenous mineralocorticoids due to the exogenous desoxycorticosterone and saline treatment.", "contents": "Corticotropin stimulation of hypertensive rats with and without arteriosclerosis. Male and female, nonarteriosclerotic (virgin) and arteriosclerotic (breeder), Sprague-Dawley rats were subjected to the hypertension-producing regimen of uninephrectomy, 1% saline drinking water, and desoxycorticosterone (Percorten) pivalate. Just before autopsy, some of the animals were given a single injection of corticotropin. The acute challenge of corticotropin caused a definite increase in free fatty acids, systolic blood pressure, creatine phosphokinase, glucose, and corticosterone. The two weeks of desoxycorticosterone and 1% saline-induced hypertension caused myocarditis and hyalinization of the coronary arteries of the nonarteriosclerotic (virgin) rats and definite exacerbation of the preexisting arteriosclerosis in breeder rats, severe myocarditis, and polyarteritis nodosa. All of the treated animals manifested lipid depletion of the zona glomerulosa indicative of reduced biosynthesis and secretion of endogenous mineralocorticoids due to the exogenous desoxycorticosterone and saline treatment."}
{"id": "PMID:214054", "title": "Nephroblastomatosis and multiple bilateral nephroblastomata. Histologic, therapeutic, and theoretical aspects.", "content": "A hemihypertrophic girl had multiple sequential bilateral Wilms' tumors over a period of five years. Diagnostic biopsy and resected specimens showed also the presence of nephroblastomatosis, presumably the substrate from which these multiple tumors arose. The patient died of complications of chemotherapy and dialysis after bilateral nephrectomy, but also had residual tumor. The relationships between nephroblastomatosis, Wilms' tumor, bilateral Wilms' tumor, and teratogenic disorders are discussed, and the therapeutic implications of the nephroblastomatosis/nephroblastoma complex are considered.", "contents": "Nephroblastomatosis and multiple bilateral nephroblastomata. Histologic, therapeutic, and theoretical aspects. A hemihypertrophic girl had multiple sequential bilateral Wilms' tumors over a period of five years. Diagnostic biopsy and resected specimens showed also the presence of nephroblastomatosis, presumably the substrate from which these multiple tumors arose. The patient died of complications of chemotherapy and dialysis after bilateral nephrectomy, but also had residual tumor. The relationships between nephroblastomatosis, Wilms' tumor, bilateral Wilms' tumor, and teratogenic disorders are discussed, and the therapeutic implications of the nephroblastomatosis/nephroblastoma complex are considered."}
{"id": "PMID:214055", "title": "Intranuclear inclusions of the human vas deferens.", "content": "Intranuclear inclusions in epithelial cells of the human vas deferens have not been well characterized or widely recognized. We studied their prevalence in an adult male population by light microscopy and characterized them using the techniques of histochemistry, electron microscopy, and electron microprobe analysis. They occurred in all cases studied, consisted of electron dense globules, contained neutral mucosubstances, and occasionally were single membrane bound. Epithelial intranuclear inclusions routinely occur in the vas deferens of sexually mature males, do not disappear with advancing age, and should not be interpreted as a pathologic finding.", "contents": "Intranuclear inclusions of the human vas deferens. Intranuclear inclusions in epithelial cells of the human vas deferens have not been well characterized or widely recognized. We studied their prevalence in an adult male population by light microscopy and characterized them using the techniques of histochemistry, electron microscopy, and electron microprobe analysis. They occurred in all cases studied, consisted of electron dense globules, contained neutral mucosubstances, and occasionally were single membrane bound. Epithelial intranuclear inclusions routinely occur in the vas deferens of sexually mature males, do not disappear with advancing age, and should not be interpreted as a pathologic finding."}
{"id": "PMID:214058", "title": "Varicella and acute cerebellar ataxia.", "content": "In two cases of varicella-associated cerebellar ataxia, varicella-zoster antigens in CSF cells were shown by an indirect immunofluorescent technique. Direct viral invasion in CNS disease complicating varicella plays an important part in pathogenesis and rules out a single immune-mediated mechanism.", "contents": "Varicella and acute cerebellar ataxia. In two cases of varicella-associated cerebellar ataxia, varicella-zoster antigens in CSF cells were shown by an indirect immunofluorescent technique. Direct viral invasion in CNS disease complicating varicella plays an important part in pathogenesis and rules out a single immune-mediated mechanism."}
{"id": "PMID:214059", "title": "Familial juvenile neuronal storage disease. New disease or variant of juvenile lipidosis?", "content": "Two patients had an illness characterized by a positive family history, juvenile onset, macular cherry-red spots, myoclonus, generalized convulsions, and cerebellar ataxia. Neither had dementia, gargoyle facies, bone or joint deformities, or visceromegaly. Vacuolated lymphocytes were not seen in the peripheral blood or bone marrow. Specimens from the rectum and vermiform appendix showed Sudan black B-, Sudan III-, and PAS-positive granules within the neurons of the myenteric plexus. On electron microscopic examination, lysosome-like bodies, membranous cytoplasmic bodies, pleomorphic lamellated bodies, dense bodies, and lipofuscin-like bodies in the neurons were seen, with a suggestion of morphological transitional forms among them. Sialoglycopeptides, especially sialic acid, were increased in the urine, but excretion of acid mucopolysaccharides was normal. Assays of lysosomal enzymes in leucocytes showed normal enzymatic activity. On the basis of the clinical, biochemical, and histological results, we suggest that these two cases and four similar cases reported in the literature be classified differently from the previously described lipidoses, although it is not known whether these cases represent a new entity or merely a clinical variant of juvenile lipidosis.", "contents": "Familial juvenile neuronal storage disease. New disease or variant of juvenile lipidosis? Two patients had an illness characterized by a positive family history, juvenile onset, macular cherry-red spots, myoclonus, generalized convulsions, and cerebellar ataxia. Neither had dementia, gargoyle facies, bone or joint deformities, or visceromegaly. Vacuolated lymphocytes were not seen in the peripheral blood or bone marrow. Specimens from the rectum and vermiform appendix showed Sudan black B-, Sudan III-, and PAS-positive granules within the neurons of the myenteric plexus. On electron microscopic examination, lysosome-like bodies, membranous cytoplasmic bodies, pleomorphic lamellated bodies, dense bodies, and lipofuscin-like bodies in the neurons were seen, with a suggestion of morphological transitional forms among them. Sialoglycopeptides, especially sialic acid, were increased in the urine, but excretion of acid mucopolysaccharides was normal. Assays of lysosomal enzymes in leucocytes showed normal enzymatic activity. On the basis of the clinical, biochemical, and histological results, we suggest that these two cases and four similar cases reported in the literature be classified differently from the previously described lipidoses, although it is not known whether these cases represent a new entity or merely a clinical variant of juvenile lipidosis."}
{"id": "PMID:214060", "title": "Reincarnation in cultured muscle of mitochondrial abnormalities. Two patients with epilepsy and lactic acidosis.", "content": "Two unrelated 9-year-old boys failed to thrive from ages 5 and 4 years, and had focal cerebral seizures followed by transcent hemipareses. Histochemistry of their muscle biopsies showed \"ragged-red\" fibers, which ultrastructurally contained clusters of mitochondria having loss of crisp delineation of crista membranes and contained amorphous inclusion material and parallel-packed cristae and sometimes paracrystalline inclusions. In the patients' cultured muscles, similar mitochondrial abnormalities were present. 2,4-Dinitrophenol, introduced to the medium of cultures of normal human muscle, produced mitochondrial abnormalities similar to those of the patients', and the medium of the patients' muscle cultures worsened the mitochondrial abnormalities. This study, in demonstrating a mitochondrial defect reproducible in the cultured muscle fibers and, therefore, intrinsic to the ragged-red muscle fibers themselves, raises the possibility of a collateral mitochondrial defect in CNS cells as part of a multicellular mitochondriopathy.", "contents": "Reincarnation in cultured muscle of mitochondrial abnormalities. Two patients with epilepsy and lactic acidosis. Two unrelated 9-year-old boys failed to thrive from ages 5 and 4 years, and had focal cerebral seizures followed by transcent hemipareses. Histochemistry of their muscle biopsies showed \"ragged-red\" fibers, which ultrastructurally contained clusters of mitochondria having loss of crisp delineation of crista membranes and contained amorphous inclusion material and parallel-packed cristae and sometimes paracrystalline inclusions. In the patients' cultured muscles, similar mitochondrial abnormalities were present. 2,4-Dinitrophenol, introduced to the medium of cultures of normal human muscle, produced mitochondrial abnormalities similar to those of the patients', and the medium of the patients' muscle cultures worsened the mitochondrial abnormalities. This study, in demonstrating a mitochondrial defect reproducible in the cultured muscle fibers and, therefore, intrinsic to the ragged-red muscle fibers themselves, raises the possibility of a collateral mitochondrial defect in CNS cells as part of a multicellular mitochondriopathy."}
{"id": "PMID:214061", "title": "Neuroanatomical and electroencephalographic correlations in Sanfilippo syndrome, type A.", "content": "Waking and all-night-sleeping electroencephalographic recordings were obtained on a boy with Sanfilippo disease, type A. The most striking abnormalities were noted during sleep and included (1) lack of progression through normal sleep stages, (2) absence of vertex waves and normal sleep spindles, (3) inability to stage sleep by the usual criteria, and (4) an unusual alteration of low-amplitude (12 to 15 Hz) activity with generalized delta frequencies. Subsequently, neuropathological examination was performed. The electrophysiological phenomena may be correlated with severe cortical involvement.", "contents": "Neuroanatomical and electroencephalographic correlations in Sanfilippo syndrome, type A. Waking and all-night-sleeping electroencephalographic recordings were obtained on a boy with Sanfilippo disease, type A. The most striking abnormalities were noted during sleep and included (1) lack of progression through normal sleep stages, (2) absence of vertex waves and normal sleep spindles, (3) inability to stage sleep by the usual criteria, and (4) an unusual alteration of low-amplitude (12 to 15 Hz) activity with generalized delta frequencies. Subsequently, neuropathological examination was performed. The electrophysiological phenomena may be correlated with severe cortical involvement."}
{"id": "PMID:214063", "title": "Effect of topical corticosteroids on ulceration in alkali-burned corneas.", "content": "Dexamethasone sodium phosphate was administered topically to one eye of rabbits with bilateral alkali corneal burns, and saline solution was administered to the contralateral eye. Topical steroids were also administered in animals with moderate corneal ulcers and were found to enhance the severity of ulceration when given during the second and third weeks following the burn. If the corticosteroids were given daily in the first six days or in the fourth and fifth weeks following the burn, they did not have an adverse effect on the cornea. Corticosteroids can be used intensively during the first week following an alkali burn, without increasing the risk of corneal melting. The mechanism for the enhancement of corneal ulceration is not a direct augmentation of collagenase activity, but probably involves the inhibition of repair processes.", "contents": "Effect of topical corticosteroids on ulceration in alkali-burned corneas. Dexamethasone sodium phosphate was administered topically to one eye of rabbits with bilateral alkali corneal burns, and saline solution was administered to the contralateral eye. Topical steroids were also administered in animals with moderate corneal ulcers and were found to enhance the severity of ulceration when given during the second and third weeks following the burn. If the corticosteroids were given daily in the first six days or in the fourth and fifth weeks following the burn, they did not have an adverse effect on the cornea. Corticosteroids can be used intensively during the first week following an alkali burn, without increasing the risk of corneal melting. The mechanism for the enhancement of corneal ulceration is not a direct augmentation of collagenase activity, but probably involves the inhibition of repair processes."}
{"id": "PMID:214065", "title": "Ultrasonic visualization of breast cancer.", "content": "Ultrasonic examination of the breast with grey scale echography gives considerable information about the composition of the constituent tissues. This information alone is sometimes of major assistance in the management of the individual patient, particularly in young women with nodular breasts due to dysplastic changes. The method is complementary to the more commonly used visualization techniques and should be considered, particularly in young women, as the first imaging technique to examine palpable masses in the breast, prior to the utilization of ionizing radiation.", "contents": "Ultrasonic visualization of breast cancer. Ultrasonic examination of the breast with grey scale echography gives considerable information about the composition of the constituent tissues. This information alone is sometimes of major assistance in the management of the individual patient, particularly in young women with nodular breasts due to dysplastic changes. The method is complementary to the more commonly used visualization techniques and should be considered, particularly in young women, as the first imaging technique to examine palpable masses in the breast, prior to the utilization of ionizing radiation."}
{"id": "PMID:214066", "title": "A graph analysis of the relationship between population density and social pathology.", "content": "This article deals with systematic variables--population density and pathological effects--at the level of a community or organizational system. Existing studies of the relationship between population density and social pathology (e.g., mortality, mental illness) in humans have failed to determine a strictly causal relationship between density and pathology in a linear model. They have not established a direct link between density and pathology in a simple two-variable, linear causal approach. Eliminating other variables by statistical control has obscured the conditions of a complex phenomenon. By incorporating socioeconomic variables into a general system model, this paper suggests that the total configuration of social organization, adaptation, previous group experience, and environment determine the effects of population density. Using a method of graph analysis, a model is presented of the relationship between population density and social pathology which has a high degree of isomorphism with the empirical situation.", "contents": "A graph analysis of the relationship between population density and social pathology. This article deals with systematic variables--population density and pathological effects--at the level of a community or organizational system. Existing studies of the relationship between population density and social pathology (e.g., mortality, mental illness) in humans have failed to determine a strictly causal relationship between density and pathology in a linear model. They have not established a direct link between density and pathology in a simple two-variable, linear causal approach. Eliminating other variables by statistical control has obscured the conditions of a complex phenomenon. By incorporating socioeconomic variables into a general system model, this paper suggests that the total configuration of social organization, adaptation, previous group experience, and environment determine the effects of population density. Using a method of graph analysis, a model is presented of the relationship between population density and social pathology which has a high degree of isomorphism with the empirical situation."}
{"id": "PMID:214091", "title": "Electron-microscopic evidence for particles smaller than 250 A in very low density lipoproteins of human plasma.", "content": "Particle size distributions of very low density lipoproteins (VLDL) in man were examined by electron microscopy. A comparison was made between normolipidemic and hyperlipidemic subjects. The results showed that the VLDL fraction frequently contained particles between 100--250 A in diameter and in some cases particles less than 100 A were observed.", "contents": "Electron-microscopic evidence for particles smaller than 250 A in very low density lipoproteins of human plasma. Particle size distributions of very low density lipoproteins (VLDL) in man were examined by electron microscopy. A comparison was made between normolipidemic and hyperlipidemic subjects. The results showed that the VLDL fraction frequently contained particles between 100--250 A in diameter and in some cases particles less than 100 A were observed."}
{"id": "PMID:214092", "title": "Coxsackievirus B cardiopathy and angiopathy in the hypercholesterolemic host.", "content": "Studies on the pathogenic potential of the human cardiotropic enterovirus, coxsackievirus B5, show that this agent localizes and replicates in the aorta of mice. Nutritionally-induced hypercholesterolemia leads to an increased replication and persistence of virus in tissues, specifically the aorta. Coxsackievirus B cardiopathy is markedly augmented in the hypercholesterolemic host, resulting in a persistent cardiomyolysis which is not evident in virus-infected animals with normal cholesterol levels. Pathological changes in the aorta become evident only months after the acute infection, and only in hypercholesterolemic animals previously infected with coxsackievirus B5. Our findings of coxsackievirus B-induced angiopathy and cardiopathy in the hypercholesterolemic host extend the known pathogenic range of these human viruses, and further emphasizes their potential as etiological agents of cardiovascular disease.", "contents": "Coxsackievirus B cardiopathy and angiopathy in the hypercholesterolemic host. Studies on the pathogenic potential of the human cardiotropic enterovirus, coxsackievirus B5, show that this agent localizes and replicates in the aorta of mice. Nutritionally-induced hypercholesterolemia leads to an increased replication and persistence of virus in tissues, specifically the aorta. Coxsackievirus B cardiopathy is markedly augmented in the hypercholesterolemic host, resulting in a persistent cardiomyolysis which is not evident in virus-infected animals with normal cholesterol levels. Pathological changes in the aorta become evident only months after the acute infection, and only in hypercholesterolemic animals previously infected with coxsackievirus B5. Our findings of coxsackievirus B-induced angiopathy and cardiopathy in the hypercholesterolemic host extend the known pathogenic range of these human viruses, and further emphasizes their potential as etiological agents of cardiovascular disease."}
{"id": "PMID:214093", "title": "Cholesterol ester exchange between human plasma high and low density lipoproteins mediated by a plasma protein factor.", "content": "Although unesterified cholesterol and phospholipids exchange freely, a protein factor from the d greater than 1.25 g/ml plasma fraction was found to be necessary for cholesterol esters to transfer from HDL to LDL. This transfer was reversible, time-dependent and a function of the concentration of the d greater than 1.25 fraction, but independent of lecithin : cholesterol acyltransferase reaction. The transfer represented an equilibration of molecules, but no net mass transfer of cholesterol esters could be demonstrated from HDL to LDL.", "contents": "Cholesterol ester exchange between human plasma high and low density lipoproteins mediated by a plasma protein factor. Although unesterified cholesterol and phospholipids exchange freely, a protein factor from the d greater than 1.25 g/ml plasma fraction was found to be necessary for cholesterol esters to transfer from HDL to LDL. This transfer was reversible, time-dependent and a function of the concentration of the d greater than 1.25 fraction, but independent of lecithin : cholesterol acyltransferase reaction. The transfer represented an equilibration of molecules, but no net mass transfer of cholesterol esters could be demonstrated from HDL to LDL."}
{"id": "PMID:214094", "title": "Metabolism of esterified cholesterol in the plasma very low density lipoproteins of the rabbit.", "content": "The in vivo metabolism of esterified cholesterol and triglyceride in plasma very low density lipoproteins (VLDL) has been studied in postabsorptive rabbits injected with endogenously 3H-labelled preparations of VLDL. The rates at which the injected esterified [3H]cholesterol and [3H]triglyceride were removed from the recipient VLDL fraction were remarkably similar. But, whereas most of the [3H]triglyceride was rapidly lost from the plasma compartment, more than 60% of the esterified [3H]cholesterol removed from VLDL was recovered in the plasma low density lipoprotein (LDL) and high density lipoprotein (HDL) fractions, an observation in direct contrast to previous findings in rats and guinea pigs in which hepatic uptake accounted for the major proportion of esterified cholesterol removed from VLDL. The appearance of VLDL-esterified [3H]cholesterol in rabbit LDL was quite compatible with the well-documented catabolic conversion of VLDL to LDL. The appearance in HDL, on the other hand, could not be so explained and was further investigated in studies performed in vitro. It was found that, concurrent with a net mass transfer of esterified cholesterol from HDL to VLDL, there was a much more rapid transfer of esterified [3H]cholesterol in the reverse direction, implying the existence of a process of molecular exchange of esterified cholesterol between the two fractions, analogous to that recently described between VLDL and LDL.", "contents": "Metabolism of esterified cholesterol in the plasma very low density lipoproteins of the rabbit. The in vivo metabolism of esterified cholesterol and triglyceride in plasma very low density lipoproteins (VLDL) has been studied in postabsorptive rabbits injected with endogenously 3H-labelled preparations of VLDL. The rates at which the injected esterified [3H]cholesterol and [3H]triglyceride were removed from the recipient VLDL fraction were remarkably similar. But, whereas most of the [3H]triglyceride was rapidly lost from the plasma compartment, more than 60% of the esterified [3H]cholesterol removed from VLDL was recovered in the plasma low density lipoprotein (LDL) and high density lipoprotein (HDL) fractions, an observation in direct contrast to previous findings in rats and guinea pigs in which hepatic uptake accounted for the major proportion of esterified cholesterol removed from VLDL. The appearance of VLDL-esterified [3H]cholesterol in rabbit LDL was quite compatible with the well-documented catabolic conversion of VLDL to LDL. The appearance in HDL, on the other hand, could not be so explained and was further investigated in studies performed in vitro. It was found that, concurrent with a net mass transfer of esterified cholesterol from HDL to VLDL, there was a much more rapid transfer of esterified [3H]cholesterol in the reverse direction, implying the existence of a process of molecular exchange of esterified cholesterol between the two fractions, analogous to that recently described between VLDL and LDL."}
{"id": "PMID:214098", "title": "Mixed mesodermal tumour of the cervix uteri. Case report.", "content": "A 44-year-old African female with a mixed mesodermal tumour of the cervix is described and the literature briefly reviewed.", "contents": "Mixed mesodermal tumour of the cervix uteri. Case report. A 44-year-old African female with a mixed mesodermal tumour of the cervix is described and the literature briefly reviewed."}
{"id": "PMID:214099", "title": "Carcinoma of the dorsum of the tongue: a rarity or misdiagnosis.", "content": "Benign lesions occurring on the dorsum of the tongue have at times been diagnosed as carcinoma. A retrospective investigation into the problem is described and the clinical and histological difficulties that arise in the diagnosis of these lesions are discussed. It is concluded that the occurrence of primary carcinoma on the dorsum of the tongue is a rare entity. It may be erroneously diagnosed in cases of median rhomboid glossitis, granular cell myoblastoma and any other lesion associated with pseudoepitheliomatous hyperplasia. These conditions should always be considered when examining lesions in this location. Histological diagnosis, although difficult, is greatly facilitated by good biopsy technique but, above all, good liaison between surgeon, radiotherapist and pathologist is essential if these mistakes in diagnosis are to be avoided.", "contents": "Carcinoma of the dorsum of the tongue: a rarity or misdiagnosis. Benign lesions occurring on the dorsum of the tongue have at times been diagnosed as carcinoma. A retrospective investigation into the problem is described and the clinical and histological difficulties that arise in the diagnosis of these lesions are discussed. It is concluded that the occurrence of primary carcinoma on the dorsum of the tongue is a rare entity. It may be erroneously diagnosed in cases of median rhomboid glossitis, granular cell myoblastoma and any other lesion associated with pseudoepitheliomatous hyperplasia. These conditions should always be considered when examining lesions in this location. Histological diagnosis, although difficult, is greatly facilitated by good biopsy technique but, above all, good liaison between surgeon, radiotherapist and pathologist is essential if these mistakes in diagnosis are to be avoided."}
{"id": "PMID:214100", "title": "Cryosurgery in the management of intractable facial pain.", "content": "The biological sequelae to the experimental freezing of peripheral nerves have been shown to differ in several respects from those following other types of nerve injury. A clinical application of these effects utilising the extreme low temperature produced by modern cryosurgical equipment is proposed and a preliminary evaluation is made.", "contents": "Cryosurgery in the management of intractable facial pain. The biological sequelae to the experimental freezing of peripheral nerves have been shown to differ in several respects from those following other types of nerve injury. A clinical application of these effects utilising the extreme low temperature produced by modern cryosurgical equipment is proposed and a preliminary evaluation is made."}
{"id": "PMID:214095", "title": "[Congenital cardiopathies and associated bone abnormalities].", "content": "The study included six infants and one adult of congenital cardiovascular anomalies and malformations of the osseum system. In three cases with family pedigree studied, an autosomal dominant character was found; all of them had interauricular defect septum and characteristic congenital deformities of the thumb with polydactyly and one with affection in upper and lower extremities. In the other four patients without family study, interauricular septal defect and transposition of vessels was proved; the osseum malformations were radium agenesia, polydactyly and thumb agenesia. The importance of the genes and the environmental participation and etiopathogenic mechanism are discussed. The prognostic is focussed within type and severity of the congenital cardiac defect; in this study, two infants died within 3 and 7 months of heart failure. These congenital malformations were proved to have autosomal dominant inheritance; we recommend the familial study in all these cases.", "contents": "[Congenital cardiopathies and associated bone abnormalities]. The study included six infants and one adult of congenital cardiovascular anomalies and malformations of the osseum system. In three cases with family pedigree studied, an autosomal dominant character was found; all of them had interauricular defect septum and characteristic congenital deformities of the thumb with polydactyly and one with affection in upper and lower extremities. In the other four patients without family study, interauricular septal defect and transposition of vessels was proved; the osseum malformations were radium agenesia, polydactyly and thumb agenesia. The importance of the genes and the environmental participation and etiopathogenic mechanism are discussed. The prognostic is focussed within type and severity of the congenital cardiac defect; in this study, two infants died within 3 and 7 months of heart failure. These congenital malformations were proved to have autosomal dominant inheritance; we recommend the familial study in all these cases."}
{"id": "PMID:214104", "title": "Protein analysis of cardiac sarcolemma: effects of membrane-perturbing agents on membrane proteins and calcium transport.", "content": "Protein composition of cardiac sarcolemmal membranes was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Membranes were observed to contain about 20 polypeptide bands ranging from 18000 to 200 000 dalton mass. Out of these, six bands were prominent and together comprised 57% of the membrane protein. When sarcolemmal membranes, phosphorylated by [gamma-(32)P] ATP in the presence of Ca(2+) or Na+ with and without K+, were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis at pH 2.4, the band III region (Mr 105 000) of gels was found to contain active sites of monomeric Ca-ATPase and (Na,K)ATPase. Bands I (Mr greater than 200 000), II (Mr 150 000), III (Mr 105 000), and VI (Mr 47 000) were accesible to trypsin; the extent of proteolysis was dependent on the time of exposure to, and the concentration of, trypsin (i.e, ratio of sarcolemmal protein/trypsin). Addition of molar sucrose protected sarcolemmal proteins from the tryptic proteolysis. Calcium transport was reduced by the action of trypsin; the degree of reduction was influenced by the time of exposure of membranes to trypsin as well as the concentration of trypsin. (Mg,Ca)ATPase activity, on the other hand, was elevated moderately at lower concentration and reduced at higher concentration of trypsin. Treatment with phospholipase C cium transport and (Mg,Ca)ATPase activity; electrophoretic patterns were unaffected by this treatment. Addition of lecithin to phospholipase C treated membranes produced a moderate increase in calcium transport. Exposure to Triton X-100 (1%) specifically solubilized three protein bands (Mr90 000, 67 000, and 57 000), whereas exposure to deoxycholate (1%) preferentially solubilized high-molecular-weight proteins, including band III (Mr 105 000); Lubrol-PX (1%) caused nonspecific solubilization of proteins, although the extent of solubilization with Lubrol-PX was considerably less than with either Triton or deoxycholate.", "contents": "Protein analysis of cardiac sarcolemma: effects of membrane-perturbing agents on membrane proteins and calcium transport. Protein composition of cardiac sarcolemmal membranes was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Membranes were observed to contain about 20 polypeptide bands ranging from 18000 to 200 000 dalton mass. Out of these, six bands were prominent and together comprised 57% of the membrane protein. When sarcolemmal membranes, phosphorylated by [gamma-(32)P] ATP in the presence of Ca(2+) or Na+ with and without K+, were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis at pH 2.4, the band III region (Mr 105 000) of gels was found to contain active sites of monomeric Ca-ATPase and (Na,K)ATPase. Bands I (Mr greater than 200 000), II (Mr 150 000), III (Mr 105 000), and VI (Mr 47 000) were accesible to trypsin; the extent of proteolysis was dependent on the time of exposure to, and the concentration of, trypsin (i.e, ratio of sarcolemmal protein/trypsin). Addition of molar sucrose protected sarcolemmal proteins from the tryptic proteolysis. Calcium transport was reduced by the action of trypsin; the degree of reduction was influenced by the time of exposure of membranes to trypsin as well as the concentration of trypsin. (Mg,Ca)ATPase activity, on the other hand, was elevated moderately at lower concentration and reduced at higher concentration of trypsin. Treatment with phospholipase C cium transport and (Mg,Ca)ATPase activity; electrophoretic patterns were unaffected by this treatment. Addition of lecithin to phospholipase C treated membranes produced a moderate increase in calcium transport. Exposure to Triton X-100 (1%) specifically solubilized three protein bands (Mr90 000, 67 000, and 57 000), whereas exposure to deoxycholate (1%) preferentially solubilized high-molecular-weight proteins, including band III (Mr 105 000); Lubrol-PX (1%) caused nonspecific solubilization of proteins, although the extent of solubilization with Lubrol-PX was considerably less than with either Triton or deoxycholate."}
{"id": "PMID:214106", "title": "Sedimentation characteristics of the scrapie agent from murine spleen and brain.", "content": "Sedimentation profiles of the scrapie agent in extracts of murine spleen and brain were determined by analytical differential centrifugation. Infectivity profiles of the agent from the two tissues were similar. Sedimentation of the agent was not substantially altered by detergent treatment with sodium deoxycholate. In the presence of detergent, centrifugation at an omega2t value of 3.0 x 1010 rad2/s in a fixed-angle rotor sedimented 90% of the agent. Comparative studies with radioisotopically labeled Simian virus 40 showed that centrifugation at an omega2t value of 1.6 x 10(10) rad2/s removed 90% of the virions. The sedimentation profile of the scrapie agent was similar to that observed for cellular ribosomal RNA. Heating infectious extracts of spleen to 80 degrees C for 30 min resulted in the destruction of 95% of the RNA while sedimentation of the scrapie agent was unchanged. These studies establish a limited range of particle sizes for the scrapie agent.", "contents": "Sedimentation characteristics of the scrapie agent from murine spleen and brain. Sedimentation profiles of the scrapie agent in extracts of murine spleen and brain were determined by analytical differential centrifugation. Infectivity profiles of the agent from the two tissues were similar. Sedimentation of the agent was not substantially altered by detergent treatment with sodium deoxycholate. In the presence of detergent, centrifugation at an omega2t value of 3.0 x 1010 rad2/s in a fixed-angle rotor sedimented 90% of the agent. Comparative studies with radioisotopically labeled Simian virus 40 showed that centrifugation at an omega2t value of 1.6 x 10(10) rad2/s removed 90% of the virions. The sedimentation profile of the scrapie agent was similar to that observed for cellular ribosomal RNA. Heating infectious extracts of spleen to 80 degrees C for 30 min resulted in the destruction of 95% of the RNA while sedimentation of the scrapie agent was unchanged. These studies establish a limited range of particle sizes for the scrapie agent."}
{"id": "PMID:214108", "title": "Tyrosyl-base-phenylalanyl intercalation in gene 5 protein-DNA complexes: proton nuclear magnetic resonance of selectively deuterated gene 5 protein.", "content": "The interactions of oligodeoxynucleotides with the aromatic residues of gene 5 protein in complexes with d(pA)8 and d(pT)8 have been determined by 1H NMR of the protein in which the five tyrosyl residues have been selectively deuterated either in the 2,6 or the 3,5 positions. Only the 3,5 protons of the three surface tyrosyls (26, 41, and 56) interact with the bases. The remainder of the aromatic protons undergoing base-dependent upfield ring-current shifts on complex formation are phenylalanyl protons, assigned to Phe(13) on the basis of model building. 19F NMR of the complexes of the m-fluorotyrosyl-labeled protein with d(pT)4 and d(pA)8 confirms the presence of ring-current perturbations of nuclei at the 3,5-tyrosyl positions of the three surface tyrosyls. Differential expression of the 19F(1H) nuclear Overhauser effect confirms the presence of two buried and three surface tyrosyl residues. A new model of the DNA binding groove is presented involving Tyr(26)-base-Phe(13) intercalation.", "contents": "Tyrosyl-base-phenylalanyl intercalation in gene 5 protein-DNA complexes: proton nuclear magnetic resonance of selectively deuterated gene 5 protein. The interactions of oligodeoxynucleotides with the aromatic residues of gene 5 protein in complexes with d(pA)8 and d(pT)8 have been determined by 1H NMR of the protein in which the five tyrosyl residues have been selectively deuterated either in the 2,6 or the 3,5 positions. Only the 3,5 protons of the three surface tyrosyls (26, 41, and 56) interact with the bases. The remainder of the aromatic protons undergoing base-dependent upfield ring-current shifts on complex formation are phenylalanyl protons, assigned to Phe(13) on the basis of model building. 19F NMR of the complexes of the m-fluorotyrosyl-labeled protein with d(pT)4 and d(pA)8 confirms the presence of ring-current perturbations of nuclei at the 3,5-tyrosyl positions of the three surface tyrosyls. Differential expression of the 19F(1H) nuclear Overhauser effect confirms the presence of two buried and three surface tyrosyl residues. A new model of the DNA binding groove is presented involving Tyr(26)-base-Phe(13) intercalation."}
{"id": "PMID:214109", "title": "An EPR analysis of cyanide-resistant mitochondria isolated from the mutant poky strain of Neurospora crassa.", "content": "An analysis of the paramagnetic components present in mitochondria isolated from the poky mutant of Neurospora crassa is described. The study was undertaken with a view to shedding light on the nature of the cyanide- and antimycin A-resistant alternative terminal oxidase which is present in these preparations. Of the ferredoxin-type iron-sulfure centers, only Centers S-1 and S-2 of succinate dehydrogenase could be detected in significant quantities. Paramagnetic centers attributable to Site I were virtually absent. In the oxidized state, at least two 'high potential iron sulfur' centers could be distinguished and these were attributed to Center S-3 of succinate dehydrogenase and a second component analogous to that found in mammalian systems. Much of the Center S-3 signal was in a highly distorted state which was apparently dependent upon the presence of an accompanying free radical species. At lower field positions,  a succinate-reducible signal peaking around g = 3.15 was found. This signal is caused by a low spin heme species, presumably the cytochrome c which is the only major cytochrome in these mitochondria. At even lower field positions, signals attributable to iron in a field of low symmetry at g = 4.3 and multiple high spin heme species around g = 6, could be distinguished. The effects of salicylhydroxamic acid, an inhibitor of the alternative oxidase, were tested on these components. Effects could be seen on at least one high spin heme component and also partially upon the distorted Center S-3 signal converting part of it to a signal indistinguishable from center S-3. Some increase in the g = 4.3 iron signal was also noted. No effects of the inhibitor on the ferredoxin-type centers were detected.", "contents": "An EPR analysis of cyanide-resistant mitochondria isolated from the mutant poky strain of Neurospora crassa. An analysis of the paramagnetic components present in mitochondria isolated from the poky mutant of Neurospora crassa is described. The study was undertaken with a view to shedding light on the nature of the cyanide- and antimycin A-resistant alternative terminal oxidase which is present in these preparations. Of the ferredoxin-type iron-sulfure centers, only Centers S-1 and S-2 of succinate dehydrogenase could be detected in significant quantities. Paramagnetic centers attributable to Site I were virtually absent. In the oxidized state, at least two 'high potential iron sulfur' centers could be distinguished and these were attributed to Center S-3 of succinate dehydrogenase and a second component analogous to that found in mammalian systems. Much of the Center S-3 signal was in a highly distorted state which was apparently dependent upon the presence of an accompanying free radical species. At lower field positions,  a succinate-reducible signal peaking around g = 3.15 was found. This signal is caused by a low spin heme species, presumably the cytochrome c which is the only major cytochrome in these mitochondria. At even lower field positions, signals attributable to iron in a field of low symmetry at g = 4.3 and multiple high spin heme species around g = 6, could be distinguished. The effects of salicylhydroxamic acid, an inhibitor of the alternative oxidase, were tested on these components. Effects could be seen on at least one high spin heme component and also partially upon the distorted Center S-3 signal converting part of it to a signal indistinguishable from center S-3. Some increase in the g = 4.3 iron signal was also noted. No effects of the inhibitor on the ferredoxin-type centers were detected."}
{"id": "PMID:214110", "title": "The orientation of membrane bound radicals: an EPR investigation of magnetically ordered spinach chloroplasts.", "content": "The orientation of membrane-bound radicals in spinach chloroplasts is examined by electron paramagnetic resonance (EPR) spectroscopy of chloroplasts oriented by magnetic fields. Several of the membrane-bound radicals which possess g-tensor anisotropy display EPR signals with a marked dependence on the orientation of the membranes relative to the applied EPR field. The fraction of oxidized and reduced plastocyanin, P-700, iron-sulfur proteins A and B, and the X center, an early acceptor of Photosystem I, can be controlled by the light intensity during steady-state illumination and can be trapped by cooling. The X center can be photoreduced and trapped in the absence of strong reductants and high pH, conditions previously found necessary for its detection. These results confirm its role as an early electron acceptor in P-700 photo-oxidation. X is oriented with its smallest principal g-tensor axis (gx) predominantly parallel to the normal to the thylakoid membrane, the same orientation as was found for an early electron acceptor based on time-resolved electron spin polarization studies. We propose that the X center is the first example of a high potential iron-sulfur protein which functions in electron transfer in its 'superreduced' state. We present evidence which suggests that iron-sulfur proteins A and B are 4Fe-4S clusters in an 8Fe-8S protein. Center B is oriented with gy predominantly normal to the membrane plane. The spectra of center A and plastocyanin do not show significant changes with sample orientation. In the case of plastocyanin, this may indicate a lack of molecular orientation. The absence of an orientation effect for reduced center A is reconcilable with a 4Fe-4S geometry, provided that the electron obtained upon reduction can be shared between any pair of Fe atoms in the center. Orientation of the 'Rieske' iron-sulfur protein is also observed. It has axial symmetry with g parallel close to the plane of the membrane. A model is proposed for the organization of these proteins in the thylakoid membrane. A new EPR signal was observed in oriented chloroplasts. This broad unresolved resonance displays a g value of 3.2 when the membrane normal is parallel to the field. It shifts to g = 1.9 when the membrane normal is perpendicular to the field. The signal is sensitive to illumination and to washing of the thylakoid membranes of broken chloroplasts. We suggest that there is a relation between this signal and the water-oxidizing enzyme system.", "contents": "The orientation of membrane bound radicals: an EPR investigation of magnetically ordered spinach chloroplasts. The orientation of membrane-bound radicals in spinach chloroplasts is examined by electron paramagnetic resonance (EPR) spectroscopy of chloroplasts oriented by magnetic fields. Several of the membrane-bound radicals which possess g-tensor anisotropy display EPR signals with a marked dependence on the orientation of the membranes relative to the applied EPR field. The fraction of oxidized and reduced plastocyanin, P-700, iron-sulfur proteins A and B, and the X center, an early acceptor of Photosystem I, can be controlled by the light intensity during steady-state illumination and can be trapped by cooling. The X center can be photoreduced and trapped in the absence of strong reductants and high pH, conditions previously found necessary for its detection. These results confirm its role as an early electron acceptor in P-700 photo-oxidation. X is oriented with its smallest principal g-tensor axis (gx) predominantly parallel to the normal to the thylakoid membrane, the same orientation as was found for an early electron acceptor based on time-resolved electron spin polarization studies. We propose that the X center is the first example of a high potential iron-sulfur protein which functions in electron transfer in its 'superreduced' state. We present evidence which suggests that iron-sulfur proteins A and B are 4Fe-4S clusters in an 8Fe-8S protein. Center B is oriented with gy predominantly normal to the membrane plane. The spectra of center A and plastocyanin do not show significant changes with sample orientation. In the case of plastocyanin, this may indicate a lack of molecular orientation. The absence of an orientation effect for reduced center A is reconcilable with a 4Fe-4S geometry, provided that the electron obtained upon reduction can be shared between any pair of Fe atoms in the center. Orientation of the 'Rieske' iron-sulfur protein is also observed. It has axial symmetry with g parallel close to the plane of the membrane. A model is proposed for the organization of these proteins in the thylakoid membrane. A new EPR signal was observed in oriented chloroplasts. This broad unresolved resonance displays a g value of 3.2 when the membrane normal is parallel to the field. It shifts to g = 1.9 when the membrane normal is perpendicular to the field. The signal is sensitive to illumination and to washing of the thylakoid membranes of broken chloroplasts. We suggest that there is a relation between this signal and the water-oxidizing enzyme system."}
{"id": "PMID:214112", "title": "Specific D-glucose transport in sarcolemma vesicles.", "content": "The sarcolemmal fraction prepared from rat skeletal muscle consists of osmotically active vesicles that accumulate D-glucose in preference to L-glucose, apparently by facilitated diffusion into intravesicular space. Stereospecific D-glucose uptake by these vesicles is a saturable rpocess, inhibited by phloridzin, by cytochalasin B, and by certain sugars, and enhanced by counterflow. An additional leak pathway permits entry of both D- and L-glucose into the vesicles. Stereospecific D-glucose transport by sarcolemmal vesicles is enhanced to a small extent by insulin, provided the hormone is administered prior to cell disruption. In membranes prepared from insulin-pretreated muscle, Ca2+ produces a small further enhancement. Local anesthetics preferentially inhibit stereospecific D-glucose transport. Apparent uptake of both D- and L-glucose is greater when vesicles are suspended in salt solutions rather than sucrose, an effect attributed to increased functional vesicular volume.", "contents": "Specific D-glucose transport in sarcolemma vesicles. The sarcolemmal fraction prepared from rat skeletal muscle consists of osmotically active vesicles that accumulate D-glucose in preference to L-glucose, apparently by facilitated diffusion into intravesicular space. Stereospecific D-glucose uptake by these vesicles is a saturable rpocess, inhibited by phloridzin, by cytochalasin B, and by certain sugars, and enhanced by counterflow. An additional leak pathway permits entry of both D- and L-glucose into the vesicles. Stereospecific D-glucose transport by sarcolemmal vesicles is enhanced to a small extent by insulin, provided the hormone is administered prior to cell disruption. In membranes prepared from insulin-pretreated muscle, Ca2+ produces a small further enhancement. Local anesthetics preferentially inhibit stereospecific D-glucose transport. Apparent uptake of both D- and L-glucose is greater when vesicles are suspended in salt solutions rather than sucrose, an effect attributed to increased functional vesicular volume."}
{"id": "PMID:214114", "title": "Interaction of cholesterol, phospholipid and apoprotein in high density lipoprotein recombinants.", "content": "To examine the effect of incorporation of cholesterol into high density lipoprotein (HDL) recombinants, multilamellar liposomes of 3H cholesterol/14C dimyristoyl phosphatidylcholine were incubated with the total apoprotein (apoHDL) and principal apoproteins (apoA-1 and apoA-2) of human plasma high density lipoprotein. Soluble recombinants were separated from unreacted liposomes by centrifugation and examined by differential scanning calorimetry and negative stain electron microscopy. At 27 degrees C, liposomes containing up to approx. 0.1 mol cholesterol/mol dimyristoyl phosphatidylcholine (DMPC) were readily solubilized by apoHDL, apoA-1 or apoA-2. However, the incorporation of DMPC and apoprotein into lipoprotein complexes was markedly reduced when liposomes containing a higher proportion of cholesterol were used. For recombinants prepared from apoHDL, apoA-1, or apoA-2, the equilibrium cholesterol content of complexes was approx. 45% that of the unreacted liposomes. Electron microscopy showed that for all cholesterol concentrations, HDL recombinants were predominantly lipid bilayer discs, approx. 160 X 55 A. Differential scanning calorimetry of cholesterol containing recombinants of DMPC/cholesterol/apoHDL or DMPC/cholesterol/apoA-1 showed, with increasing cholesterol content, a linear decrease in the enthalpy of the DMPC gel to liquid crystalline transition, extrapolating to zero enthalpy at 0.15 cholesterol/DMPC. The enthalpy values were markedly reduced compared to control liposomes, where the phospholipid transition extrapolated to zero enthalpy at approx. 0.45 cholesterol/DMPC. The calorimetric and solubility studies suggest that in high density lipoprotein recombinants cholesterol is excluded from 55% of DMPC molecules bound in a non-melting state by apoprotein.", "contents": "Interaction of cholesterol, phospholipid and apoprotein in high density lipoprotein recombinants. To examine the effect of incorporation of cholesterol into high density lipoprotein (HDL) recombinants, multilamellar liposomes of 3H cholesterol/14C dimyristoyl phosphatidylcholine were incubated with the total apoprotein (apoHDL) and principal apoproteins (apoA-1 and apoA-2) of human plasma high density lipoprotein. Soluble recombinants were separated from unreacted liposomes by centrifugation and examined by differential scanning calorimetry and negative stain electron microscopy. At 27 degrees C, liposomes containing up to approx. 0.1 mol cholesterol/mol dimyristoyl phosphatidylcholine (DMPC) were readily solubilized by apoHDL, apoA-1 or apoA-2. However, the incorporation of DMPC and apoprotein into lipoprotein complexes was markedly reduced when liposomes containing a higher proportion of cholesterol were used. For recombinants prepared from apoHDL, apoA-1, or apoA-2, the equilibrium cholesterol content of complexes was approx. 45% that of the unreacted liposomes. Electron microscopy showed that for all cholesterol concentrations, HDL recombinants were predominantly lipid bilayer discs, approx. 160 X 55 A. Differential scanning calorimetry of cholesterol containing recombinants of DMPC/cholesterol/apoHDL or DMPC/cholesterol/apoA-1 showed, with increasing cholesterol content, a linear decrease in the enthalpy of the DMPC gel to liquid crystalline transition, extrapolating to zero enthalpy at 0.15 cholesterol/DMPC. The enthalpy values were markedly reduced compared to control liposomes, where the phospholipid transition extrapolated to zero enthalpy at approx. 0.45 cholesterol/DMPC. The calorimetric and solubility studies suggest that in high density lipoprotein recombinants cholesterol is excluded from 55% of DMPC molecules bound in a non-melting state by apoprotein."}
{"id": "PMID:214115", "title": "Isolation of the membranes of an enterotoxigenic strain of Escherichia coli and distribution of enterotoxin activity in different subcellular fractions.", "content": "The intracellular localization of enterotoxin in Escherichia coli AP1, a strain of porcine origin which produces high levels of heat-labile, but no heat-stable enterotoxin, has been examined. The cytoplasmic and outer membranes of this strain both contained enterotoxin activity, while the membranes isolated from a serologically related non-enterotoxigenic strain (E. coli AP2) also of porcine origin, did not show enterotoxin activity. The periplasmic fraction isolated from the enterotoxigenic strain contained considerable enterotoxin activity, but this activity was associated with outer membrane fragments present in the periplasmic fraction. Thus, of the total cellular enterotoxin activity, about 55%, 15% and 30% were present in the outer membrane, cytoplasmic membrane and the cell cytoplasm, respectively. The specific activity of enterotoxin was 20 units per mg protein in the cytoplasm and 90 and 150 units per mg protein in the cytoplasmic and outer membranes, respectively.", "contents": "Isolation of the membranes of an enterotoxigenic strain of Escherichia coli and distribution of enterotoxin activity in different subcellular fractions. The intracellular localization of enterotoxin in Escherichia coli AP1, a strain of porcine origin which produces high levels of heat-labile, but no heat-stable enterotoxin, has been examined. The cytoplasmic and outer membranes of this strain both contained enterotoxin activity, while the membranes isolated from a serologically related non-enterotoxigenic strain (E. coli AP2) also of porcine origin, did not show enterotoxin activity. The periplasmic fraction isolated from the enterotoxigenic strain contained considerable enterotoxin activity, but this activity was associated with outer membrane fragments present in the periplasmic fraction. Thus, of the total cellular enterotoxin activity, about 55%, 15% and 30% were present in the outer membrane, cytoplasmic membrane and the cell cytoplasm, respectively. The specific activity of enterotoxin was 20 units per mg protein in the cytoplasm and 90 and 150 units per mg protein in the cytoplasmic and outer membranes, respectively."}
{"id": "PMID:214116", "title": "Phosphate transport by embryonic chick duodenum. Stimulation by vitamin D3.", "content": "Embryonic chick duodenum maintained in organ culture is a well-suited model for the study of vitamin D effects on inorganic phosphate (Pi) absorption. The system is sensitive to as little as 6.5 nM vitamin D3 (0.1.I.U./ml culture medium). Increased phosphate absorption is observed after 6--12 h of culture. Maximal response (133% of vitamin D-efficient control) is achieved at 24 h. Phosphate uptake by embryonic chick duodenum involves a saturable and a non-saturable component. The former displays characteristics of an active sodium-dependent transport mechanism and is also sensitive to vitamin D3.  Presence of the sterol in culture medium raises the maximal velocity from 55 to 75 nmol Pi/min per g tissue. Km remains unchanged (0.5 mM Pi). Duodena cultured in presence of inhibitors of protein synthesis (actinomycin D, alpha-amanitin and cycloheximide) display reduced rates of phosphate absorption. This treatment also prevents vitamin D3 action on phosphate transport. It is concluded that the sterol affects phosphate transport by modulation of synthesis of proteins which are functional in the Pi absorptive process.", "contents": "Phosphate transport by embryonic chick duodenum. Stimulation by vitamin D3. Embryonic chick duodenum maintained in organ culture is a well-suited model for the study of vitamin D effects on inorganic phosphate (Pi) absorption. The system is sensitive to as little as 6.5 nM vitamin D3 (0.1.I.U./ml culture medium). Increased phosphate absorption is observed after 6--12 h of culture. Maximal response (133% of vitamin D-efficient control) is achieved at 24 h. Phosphate uptake by embryonic chick duodenum involves a saturable and a non-saturable component. The former displays characteristics of an active sodium-dependent transport mechanism and is also sensitive to vitamin D3.  Presence of the sterol in culture medium raises the maximal velocity from 55 to 75 nmol Pi/min per g tissue. Km remains unchanged (0.5 mM Pi). Duodena cultured in presence of inhibitors of protein synthesis (actinomycin D, alpha-amanitin and cycloheximide) display reduced rates of phosphate absorption. This treatment also prevents vitamin D3 action on phosphate transport. It is concluded that the sterol affects phosphate transport by modulation of synthesis of proteins which are functional in the Pi absorptive process."}
{"id": "PMID:214118", "title": "The mechanism of the aminoacylation of transfer ribonucleic acid. The kinetics and stoichiometry of the lysis of aminoacyl-tRNA.", "content": "It is often stated that the aminoacylation of transfer RNA proceeds in discrete steps: (formula: see article). If this is a complete description of the reaction, the reverse overall formation of ATP should not be more rapid than the formation of Enz . (AA approximately AMP). We show for four different amino acid:tRNA ligases that lysis of AA-tRNA (with PPi and AMP) to ATP is faster than lysis of AA-tRNA (with AMP only) to Enz . (AA approximately AMP). This requires that the transition state proceeds from a quaternary complex of PPi, AMP, AA-tRNA and Enz. From the law of microscopic reversibility, this requires that in the forward reaction the AA-tRNA bond be formed before PPi leaves the enzyme complex. Therefore, the forward reaction passes through the quaternary complex Enz . ATP . AA . tRNA. (In view of recent evidence of the specific requirement of two cations, the complex is accurately described as senary).", "contents": "The mechanism of the aminoacylation of transfer ribonucleic acid. The kinetics and stoichiometry of the lysis of aminoacyl-tRNA. It is often stated that the aminoacylation of transfer RNA proceeds in discrete steps: (formula: see article). If this is a complete description of the reaction, the reverse overall formation of ATP should not be more rapid than the formation of Enz . (AA approximately AMP). We show for four different amino acid:tRNA ligases that lysis of AA-tRNA (with PPi and AMP) to ATP is faster than lysis of AA-tRNA (with AMP only) to Enz . (AA approximately AMP). This requires that the transition state proceeds from a quaternary complex of PPi, AMP, AA-tRNA and Enz. From the law of microscopic reversibility, this requires that in the forward reaction the AA-tRNA bond be formed before PPi leaves the enzyme complex. Therefore, the forward reaction passes through the quaternary complex Enz . ATP . AA . tRNA. (In view of recent evidence of the specific requirement of two cations, the complex is accurately described as senary)."}
{"id": "PMID:214119", "title": "Solubilization of 6-oxybenzo(a)pyrene radical by caffeine and DNA as studied by magnetic resonance. Observation of intermolecular charge transfer.", "content": "Crystals of 6-oxybenzo(a)pyrene free radical, formed chemically from the hydroxy derivative of the carcinogen benzo(a)pyrene, can be solubilized in aqueous solutions of DNA and of caffeine. ESR spectral evidence indicate that the radicals exist as dispersed monomers associated with DNA and with caffeine. Comparison of NMR spin-lattice and spin-spin relaxation times in the protons of caffeine has given direct evidence that a part of the unpaired electron (at least 10(-4)) is transferred from the radical to the associated caffeine molecule. Simple consideration of Mulliken's charge transfer theory, however, leads to the conclusion that the intermolecular charge transfer is not likely to be a major source of stabilization energy of the complex.", "contents": "Solubilization of 6-oxybenzo(a)pyrene radical by caffeine and DNA as studied by magnetic resonance. Observation of intermolecular charge transfer. Crystals of 6-oxybenzo(a)pyrene free radical, formed chemically from the hydroxy derivative of the carcinogen benzo(a)pyrene, can be solubilized in aqueous solutions of DNA and of caffeine. ESR spectral evidence indicate that the radicals exist as dispersed monomers associated with DNA and with caffeine. Comparison of NMR spin-lattice and spin-spin relaxation times in the protons of caffeine has given direct evidence that a part of the unpaired electron (at least 10(-4)) is transferred from the radical to the associated caffeine molecule. Simple consideration of Mulliken's charge transfer theory, however, leads to the conclusion that the intermolecular charge transfer is not likely to be a major source of stabilization energy of the complex."}
{"id": "PMID:214120", "title": "The role of cyclic 3',5'-AMP in the regulation of aminoacyl-tRNA synthetase activities in mouse uterus and liver following 17beta-oestradiol treatment. Activation of a phosphoaminoacyl-tRNA synthetase phosphatase by phosphorylation with cyclic 3',5'-AMP dependent protein kinase.", "content": "The changes in the activities of 17 aminoacyl-tRNA synthetases induced by phosphorylation [1] were reversed by the action of cyclic AMP in preparations from both uterus and liver. Cyclic AMP also inhibited the phosphorylation of aminoacyl-tRNA synthetase protein by endogenous non-cyclic AMP-dependent protein kinase and [gamma-32P]ATP. The effect was not due to a stimulation of phosphoaminoacyl-tRNA synthetase phosphatase or to an influence of cyclic AMP on aminoacyl-tRNA synthetases. The activity of phosphoaminoacyl-tRNA synthetase phosphatase was increased by treatment with endogenous cyclic AMP-dependent protein kinase, ATP and cyclic AMP. Affinity chromatography of the 32P-labeled phosphorylated phosphosynthetase phosphatase protein followed by gel electrophoresis showed that the activated phosphatase was phosphorylated. In the uterus, the changes in 17 aminoacyl-tRNA synthetase activities observed 5 min after dibutyryl cyclic AMP administration to ovariectomized mice were similar to those observed after 17beta-oestradiol treatment, whereas in the liver the changes in these activities were the opposite to those found after treatment with 17beta-oestradiol. A mechanism for the regulation of the 17 aminoacyl-tRNA synthetase activities is proposed, which suggests that the synthetase activities inhibited (group I) or stimulated (group II) by phosphorylation with a non-cyclic AMP-dependent aminoacyl-tRNA synthetase kinase are reactivated (group I) or inhibited (group II), respectively, by the action of a cyclic AMP-dependent phosphatase kinase through the increased activity of phosphorylated phosphoaminoacyl-tRNA synthetase phosphatase.", "contents": "The role of cyclic 3',5'-AMP in the regulation of aminoacyl-tRNA synthetase activities in mouse uterus and liver following 17beta-oestradiol treatment. Activation of a phosphoaminoacyl-tRNA synthetase phosphatase by phosphorylation with cyclic 3',5'-AMP dependent protein kinase. The changes in the activities of 17 aminoacyl-tRNA synthetases induced by phosphorylation [1] were reversed by the action of cyclic AMP in preparations from both uterus and liver. Cyclic AMP also inhibited the phosphorylation of aminoacyl-tRNA synthetase protein by endogenous non-cyclic AMP-dependent protein kinase and [gamma-32P]ATP. The effect was not due to a stimulation of phosphoaminoacyl-tRNA synthetase phosphatase or to an influence of cyclic AMP on aminoacyl-tRNA synthetases. The activity of phosphoaminoacyl-tRNA synthetase phosphatase was increased by treatment with endogenous cyclic AMP-dependent protein kinase, ATP and cyclic AMP. Affinity chromatography of the 32P-labeled phosphorylated phosphosynthetase phosphatase protein followed by gel electrophoresis showed that the activated phosphatase was phosphorylated. In the uterus, the changes in 17 aminoacyl-tRNA synthetase activities observed 5 min after dibutyryl cyclic AMP administration to ovariectomized mice were similar to those observed after 17beta-oestradiol treatment, whereas in the liver the changes in these activities were the opposite to those found after treatment with 17beta-oestradiol. A mechanism for the regulation of the 17 aminoacyl-tRNA synthetase activities is proposed, which suggests that the synthetase activities inhibited (group I) or stimulated (group II) by phosphorylation with a non-cyclic AMP-dependent aminoacyl-tRNA synthetase kinase are reactivated (group I) or inhibited (group II), respectively, by the action of a cyclic AMP-dependent phosphatase kinase through the increased activity of phosphorylated phosphoaminoacyl-tRNA synthetase phosphatase."}
{"id": "PMID:214121", "title": "Protein kinases and their protein substrates associated with chromatin and ribosomes in SV40-transformed rat cells.", "content": "The level of endogenous protein phosphorylation in non-histone chromosomal and ribosomal wash proteins is 7--10 times greater in SV40-transformed rat cells than in untransformed parental cells. Protein kinase activity in these proteins was fractionated by either phosphocellulose or DEAE-cellulose chromatography. One major and one minor component were detected in non-histone proteins and only one component in ribosomal wash proteins when the activity in each fraction was measured with an exogenous substrate, casein. These enzymes prefer casein to whole histone as substrate and are cyclic AMP-independent. The enzyme activity in a major peak of non-histone proteins and in ribosomal wash proteins measured with casein as substrate is 3 times greater in transformed cells than in untransformed cells, whereas pH optimum, cation requirements and apparent Km values for casein and ATP are identical or very similar in the two cell types. No significant phosphatase was detected in non-histone and ribosomal wash proteins from the two types of cell. The patterns of endogenous protein phosphorylation in these protein fractions analysed by gel electrophoresis are significantly different between these cells. These results suggest that the high level of endogenous protein phosphorylation in non-histone and ribosomal wash proteins from SV40-transformed cells is caused mainly by the increased activity of protein kinase and the nature of protein substrates.", "contents": "Protein kinases and their protein substrates associated with chromatin and ribosomes in SV40-transformed rat cells. The level of endogenous protein phosphorylation in non-histone chromosomal and ribosomal wash proteins is 7--10 times greater in SV40-transformed rat cells than in untransformed parental cells. Protein kinase activity in these proteins was fractionated by either phosphocellulose or DEAE-cellulose chromatography. One major and one minor component were detected in non-histone proteins and only one component in ribosomal wash proteins when the activity in each fraction was measured with an exogenous substrate, casein. These enzymes prefer casein to whole histone as substrate and are cyclic AMP-independent. The enzyme activity in a major peak of non-histone proteins and in ribosomal wash proteins measured with casein as substrate is 3 times greater in transformed cells than in untransformed cells, whereas pH optimum, cation requirements and apparent Km values for casein and ATP are identical or very similar in the two cell types. No significant phosphatase was detected in non-histone and ribosomal wash proteins from the two types of cell. The patterns of endogenous protein phosphorylation in these protein fractions analysed by gel electrophoresis are significantly different between these cells. These results suggest that the high level of endogenous protein phosphorylation in non-histone and ribosomal wash proteins from SV40-transformed cells is caused mainly by the increased activity of protein kinase and the nature of protein substrates."}
{"id": "PMID:214122", "title": "Genome modification in two lines of baby hamster kidney fibroblasts (BHK-21).", "content": "Reasons for the different levels of 5-methyl cytosine encountered in the DNA of two baby hamsters kidney fibroblast lines, BHK-21/C13 and BHK-21/PyY have been investigated. From enzymic studies it does not seem that there are large numbers of potentially methylatable cytosine residues in the C13 line DNA which contains a lower level of 5-methyl cytosine. Rather it is possible that the difference may be due to the reiteration in the PyY strain of certain sequences containing 5-methyl cytosine which simply occur less frequently in the other line.", "contents": "Genome modification in two lines of baby hamster kidney fibroblasts (BHK-21). Reasons for the different levels of 5-methyl cytosine encountered in the DNA of two baby hamsters kidney fibroblast lines, BHK-21/C13 and BHK-21/PyY have been investigated. From enzymic studies it does not seem that there are large numbers of potentially methylatable cytosine residues in the C13 line DNA which contains a lower level of 5-methyl cytosine. Rather it is possible that the difference may be due to the reiteration in the PyY strain of certain sequences containing 5-methyl cytosine which simply occur less frequently in the other line."}
{"id": "PMID:214123", "title": "Regulation of de novo purine synthesis in chick liver slices. Role of phosphoribosylpyrophosphate availability and of salvage purine nucleotide synthesis.", "content": "The differences between the uricotelic chick and the ureotelic rat, in the regulation of purine synthesis de novo, were studied in intact liver tissue. Chick liver, in comparison with rat liver, was found to contain a high activity of purine synthesis de novo, a high content and availability of 5-phosphoribosyl 1-pyrophosphate (PP-rib-P), comparable activity of PP-rib-P synthetase, and low activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and of adenine phosphoribosyltransferase (APRT). The results suggest that the intensive activity of the pathway of purine synthesis de novo in the chick liver is mediated by the high PP-rib-P concentration, which may be due at least in part to the relative partial deficiency of HGPRT.", "contents": "Regulation of de novo purine synthesis in chick liver slices. Role of phosphoribosylpyrophosphate availability and of salvage purine nucleotide synthesis. The differences between the uricotelic chick and the ureotelic rat, in the regulation of purine synthesis de novo, were studied in intact liver tissue. Chick liver, in comparison with rat liver, was found to contain a high activity of purine synthesis de novo, a high content and availability of 5-phosphoribosyl 1-pyrophosphate (PP-rib-P), comparable activity of PP-rib-P synthetase, and low activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and of adenine phosphoribosyltransferase (APRT). The results suggest that the intensive activity of the pathway of purine synthesis de novo in the chick liver is mediated by the high PP-rib-P concentration, which may be due at least in part to the relative partial deficiency of HGPRT."}
{"id": "PMID:214124", "title": "Magnetic susceptibility of laccases and ceruloplasmin.", "content": "1. Recent magnetic susceptibility measurements on laccase (monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) from the lacquer tree Rhus vernicifera showed a deviation from Curie behaviour above 50 K, which was taken as evidence for an antiferromagnetically coupled Cu(II)-Cu(II) pair in the oxidized enzyme. The magnetic susceptibility of this protein has been reinvestigated. Further measurements on laccase from the fungus Polyporus versicolor and human ceruloplasmin (iron(II):oxygen oxidoreductase, EC 1.16.3.1) are presented. 2. The magnetic susceptibility of fungal laccase and lacquer tree laccase can be accounted for by the EPR detectable copper ions in the temperature range 40--300 K. 3. If an antiferromagnetically coupled Cu(II)-Cu(II) pair exists in the laccases, then the coupling, expressed as --J, should be at least of the order of 300 cm-1, as deduced from the Curie dependence of the susceptibility and the sensitivity in our measurements. 4. If an analogy with the laccases is assumed for the EPR invisible copper in ceruloplasmin then a limiting value of the coupling may be deduced also in this case, with --J at least of the order of 200 cm-1.", "contents": "Magnetic susceptibility of laccases and ceruloplasmin. 1. Recent magnetic susceptibility measurements on laccase (monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) from the lacquer tree Rhus vernicifera showed a deviation from Curie behaviour above 50 K, which was taken as evidence for an antiferromagnetically coupled Cu(II)-Cu(II) pair in the oxidized enzyme. The magnetic susceptibility of this protein has been reinvestigated. Further measurements on laccase from the fungus Polyporus versicolor and human ceruloplasmin (iron(II):oxygen oxidoreductase, EC 1.16.3.1) are presented. 2. The magnetic susceptibility of fungal laccase and lacquer tree laccase can be accounted for by the EPR detectable copper ions in the temperature range 40--300 K. 3. If an antiferromagnetically coupled Cu(II)-Cu(II) pair exists in the laccases, then the coupling, expressed as --J, should be at least of the order of 300 cm-1, as deduced from the Curie dependence of the susceptibility and the sensitivity in our measurements. 4. If an analogy with the laccases is assumed for the EPR invisible copper in ceruloplasmin then a limiting value of the coupling may be deduced also in this case, with --J at least of the order of 200 cm-1."}
{"id": "PMID:214125", "title": "A rapid purification of T4 polynucleotide kinase using Blue Dextran-Sepharose chromatography.", "content": "A rapid batch procedure is described for purification of T4 polynucleotide kinase (ATP:5'-dephosphopolynucleotide 5'-phosphotransferase, EC 2.7.1.78) to near homogeneity using Blue Dextran-Sepharose chromatography. The enzyme preparation is sufficiently free of contaminating endonuclease and alkaline phosphatase activities to be suitable for radioactively labeling nucleic acids in vitro. Kinetic measurements indicate that the chromophore of Blue Dextran, Cibacron Blue F3GA, inhibits the activity of T4 polynucleotide kinase competitively with respect to single stranded DNA substrate and non-competitively with respect to the rATP substrate.", "contents": "A rapid purification of T4 polynucleotide kinase using Blue Dextran-Sepharose chromatography. A rapid batch procedure is described for purification of T4 polynucleotide kinase (ATP:5'-dephosphopolynucleotide 5'-phosphotransferase, EC 2.7.1.78) to near homogeneity using Blue Dextran-Sepharose chromatography. The enzyme preparation is sufficiently free of contaminating endonuclease and alkaline phosphatase activities to be suitable for radioactively labeling nucleic acids in vitro. Kinetic measurements indicate that the chromophore of Blue Dextran, Cibacron Blue F3GA, inhibits the activity of T4 polynucleotide kinase competitively with respect to single stranded DNA substrate and non-competitively with respect to the rATP substrate."}
{"id": "PMID:214126", "title": "Nucleosidediphosphate kinase of Escherichia coli, a periplasmic enzyme.", "content": "The ATP-ADP exchange activity previously described in a membrane farction of Escherichia coli appeared after a cold osmotic shock according to Neu and Heppel ((1965) J. Biol. Chem. 240, 3685--3692) in the shock fluid. Membranes derived from shocked cells had no activity. The enzyme responsible for this activity has been purified 125-fold and catalyzed the transfer of a phosphoryl radical from ribonucleosidetriphosphates (NTPs) to ribonucleosidediphosphates (NDPs); this is, therefore, a non-specific nucleosidediphosphate kinase (ATP:nucleosidediphosphate phosphotransferase, EC 2.7.4.6). The activity required the presence of a divalent cation, Mg2+, Mn2+ or Ca2+ at a unity mol/mol ratio of nucleotide for maximal activation. The enzyme exhibited simple saturation kinetics with respect to the phosphate donor but inhibition by excess substrate was observed upon increasing phosphate acceptor. The kinetics of the reaction indicated an ordered bi-molecular ping-pong reaction mechanism. Differential heat sensitivity of the enzyme whether it is heated alone with ATP, ADP or Mg2+ opens possibilities to study different enzyme-substrate complexes.", "contents": "Nucleosidediphosphate kinase of Escherichia coli, a periplasmic enzyme. The ATP-ADP exchange activity previously described in a membrane farction of Escherichia coli appeared after a cold osmotic shock according to Neu and Heppel ((1965) J. Biol. Chem. 240, 3685--3692) in the shock fluid. Membranes derived from shocked cells had no activity. The enzyme responsible for this activity has been purified 125-fold and catalyzed the transfer of a phosphoryl radical from ribonucleosidetriphosphates (NTPs) to ribonucleosidediphosphates (NDPs); this is, therefore, a non-specific nucleosidediphosphate kinase (ATP:nucleosidediphosphate phosphotransferase, EC 2.7.4.6). The activity required the presence of a divalent cation, Mg2+, Mn2+ or Ca2+ at a unity mol/mol ratio of nucleotide for maximal activation. The enzyme exhibited simple saturation kinetics with respect to the phosphate donor but inhibition by excess substrate was observed upon increasing phosphate acceptor. The kinetics of the reaction indicated an ordered bi-molecular ping-pong reaction mechanism. Differential heat sensitivity of the enzyme whether it is heated alone with ATP, ADP or Mg2+ opens possibilities to study different enzyme-substrate complexes."}
{"id": "PMID:214128", "title": "Peptidyl dipeptidase in rabbit brain microvessels.", "content": "The activity of peptidyl dipeptidase (peptidyldipeptide hydrolase, EC 3.4.15.1), also known as angiotensin-converting enzyme, was studied in small blood vessel preparations isolated from rabbit brain. The vascular preparation contained arterioles and capillaries and was essentially free of extravascular material. Enzymatic activity was demonstrated in microvessel homogenates using both hippuryl-histidyl-leucine and tritium-labeled angiotensin I as substrates. Activity in the microvessels was dependent on the presence of chloride ion and was sensitive to inhibition by converting enzyme inhibitors previously shown to be effective in both vivo and in vitro. Specific activity in the micro-vessels was approximately 20 times that in homogenates of brain, and was almost 60% of that found in rat lung homogenates. The data were consistent with an endothelial localication for peptidyl dipeptidase in the cerebral vasculature and supports the proposal that this enzyme has a physiological role in extrapulmonary vascular beds.", "contents": "Peptidyl dipeptidase in rabbit brain microvessels. The activity of peptidyl dipeptidase (peptidyldipeptide hydrolase, EC 3.4.15.1), also known as angiotensin-converting enzyme, was studied in small blood vessel preparations isolated from rabbit brain. The vascular preparation contained arterioles and capillaries and was essentially free of extravascular material. Enzymatic activity was demonstrated in microvessel homogenates using both hippuryl-histidyl-leucine and tritium-labeled angiotensin I as substrates. Activity in the microvessels was dependent on the presence of chloride ion and was sensitive to inhibition by converting enzyme inhibitors previously shown to be effective in both vivo and in vitro. Specific activity in the micro-vessels was approximately 20 times that in homogenates of brain, and was almost 60% of that found in rat lung homogenates. The data were consistent with an endothelial localication for peptidyl dipeptidase in the cerebral vasculature and supports the proposal that this enzyme has a physiological role in extrapulmonary vascular beds."}
{"id": "PMID:214129", "title": "Effects of polyamines on partial reactions of membrane (Na+ + K+)-ATPase.", "content": "Spermine and spermidine inhibit the (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) reaction so that the effect increases as the ionic content due to Na+ and K+ in the reaction is reduced. Several other amines inhibit (Na+ + K+)-ATPase to varying degress and methylglyoxal-bis-(guanylhydrazone) was the most potent inhibitor among those tested. The inhibition by polyamines of the ATPase is uncompetitive with respect to Mg2+ and ATP activation of the reaction. Various naturally occurring polyamines and other amines inhibited Na+ activation of (Na+ + K+)-ATPase as well as Na+-dependent phosphoenzyme formation in an apparently competitive manner with respect to Na+. Likewise, K+-activation of (Na+ + K+)-ATPase as well as K+-p-nitrophenyl phosphatase was inhibited in an apparently competitive manner with respect to K+. Both the cation charge and structure (e.g., aliphatic chain length) may contribute to the inhibitory effects of the amines; however, Na+ sites appear to be more sensitive to cation charge than the aliphatic chain length of the amine, whereas the opposite appears to be true for K+ sites. The results do not indicate a specific effect of polyamines on (Na+ + K+)-ATPase or its partial reactions.", "contents": "Effects of polyamines on partial reactions of membrane (Na+ + K+)-ATPase. Spermine and spermidine inhibit the (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) reaction so that the effect increases as the ionic content due to Na+ and K+ in the reaction is reduced. Several other amines inhibit (Na+ + K+)-ATPase to varying degress and methylglyoxal-bis-(guanylhydrazone) was the most potent inhibitor among those tested. The inhibition by polyamines of the ATPase is uncompetitive with respect to Mg2+ and ATP activation of the reaction. Various naturally occurring polyamines and other amines inhibited Na+ activation of (Na+ + K+)-ATPase as well as Na+-dependent phosphoenzyme formation in an apparently competitive manner with respect to Na+. Likewise, K+-activation of (Na+ + K+)-ATPase as well as K+-p-nitrophenyl phosphatase was inhibited in an apparently competitive manner with respect to K+. Both the cation charge and structure (e.g., aliphatic chain length) may contribute to the inhibitory effects of the amines; however, Na+ sites appear to be more sensitive to cation charge than the aliphatic chain length of the amine, whereas the opposite appears to be true for K+ sites. The results do not indicate a specific effect of polyamines on (Na+ + K+)-ATPase or its partial reactions."}
{"id": "PMID:214130", "title": "UDP-glucose 4-epimerase from Saccharomyces fragilis. Involvement of sulfhydryl group(s) at the active site.", "content": "UDPglucose-4-epimerase (EC 5.1.3.2) from Saccharomyces fragilis is inactivated by 0.1 mM 5,5'-dithiobis-(2-nitrobenzoate) in 6 min. Unlike p-chloromercuribenzoate-inactivated or heat-inactivated enzymes, the dithiobisnitrobenzoate-inactivated enzyme retains the dimeric structure and NAD is not dissociated from the protein moiety. Inactivation of the enzyme by dithiobisnitrobenzoate can not therefore be attributed to any subsequent loss of structural integrity or to the detachment of the cofactor from the apoenzyme. The inactivated enzyme can be almost fully reactivated in the presence of mercaptoethanol and characteristic properties of native enzyme are regained. The inactivation by dithiobisnitrobenzoate can be substantially protected by UDPglucose or UDPgalactose indicating a possible critical involvement of one or more sulfhydryl groups at the active site.", "contents": "UDP-glucose 4-epimerase from Saccharomyces fragilis. Involvement of sulfhydryl group(s) at the active site. UDPglucose-4-epimerase (EC 5.1.3.2) from Saccharomyces fragilis is inactivated by 0.1 mM 5,5'-dithiobis-(2-nitrobenzoate) in 6 min. Unlike p-chloromercuribenzoate-inactivated or heat-inactivated enzymes, the dithiobisnitrobenzoate-inactivated enzyme retains the dimeric structure and NAD is not dissociated from the protein moiety. Inactivation of the enzyme by dithiobisnitrobenzoate can not therefore be attributed to any subsequent loss of structural integrity or to the detachment of the cofactor from the apoenzyme. The inactivated enzyme can be almost fully reactivated in the presence of mercaptoethanol and characteristic properties of native enzyme are regained. The inactivation by dithiobisnitrobenzoate can be substantially protected by UDPglucose or UDPgalactose indicating a possible critical involvement of one or more sulfhydryl groups at the active site."}
{"id": "PMID:214131", "title": "Involvement of superoxide in the catalytic cycle of diamine oxidase.", "content": "The reaction of pig kidney diamine oxidase (amine:oxygen oxidoreductase (deaminating) (pyridoxal-containing), EC 1.4.3.6) could be significantly inhibited by superoxide dismutase active copper chelates but not by native 2Cu,2Zn-superoxide dimutase (cuprein). The ligands alone as well as Cd2+, a heavy metal of similar toxicity to Cu2+, showed no inhibition whatsoever. This indicates that .O-2 participates in the catalytic cycle and is produced at a site scarcely accessible to such a large molecule as cuprein. A mechanism for the second, aerobic step of the diamine oxidase reaction is suggested.", "contents": "Involvement of superoxide in the catalytic cycle of diamine oxidase. The reaction of pig kidney diamine oxidase (amine:oxygen oxidoreductase (deaminating) (pyridoxal-containing), EC 1.4.3.6) could be significantly inhibited by superoxide dismutase active copper chelates but not by native 2Cu,2Zn-superoxide dimutase (cuprein). The ligands alone as well as Cd2+, a heavy metal of similar toxicity to Cu2+, showed no inhibition whatsoever. This indicates that .O-2 participates in the catalytic cycle and is produced at a site scarcely accessible to such a large molecule as cuprein. A mechanism for the second, aerobic step of the diamine oxidase reaction is suggested."}
{"id": "PMID:214132", "title": "Tryptophan fluorescence of (Na+ + K+)-ATPase as a tool for study of the enzyme mechanism.", "content": "1. The protein fluorescence intensity of (Na+ + K+)-ATPase is enhanced following binding of K+ at low concentrations. The properties of the response suggest that one or a few tryptophan residues are affected by a conformational transition between the K-bound form E2 . (K) and a Na-bound form E1 . Na. 2. The rate of the conformational transition E2 . (K) leads to E . Na has been measured with a stopped-flow fluorimeter by exploiting the difference in fluorescence of the two states. In the absence of ATP the rate is very slow, but it is greatly accelerated by binding of ATP to a low affinity site. 3. Transient changes in tryptophan fluorescence accompany hydrolysis of ATP at low concentrations, in media containing Mg2+, Na+ and K+. The fluorescence response reflects interconversion between the initial enzyme conformation, E1 . Na and the steady-state turnover intermediate E2 . (K). 4. The phosphorylated intermediate, E2P can be detected by a fluorescence increase accompanying hydrolysis of ATP in media containing Mg2+ and Na+ but no K+. 5. The conformational states and reaction mechanism of the (Na+ + K+)-ATPase are discussed in the light of this work. The results permit a comparison of the behaviour of the enzyme at both low and high nucleotide concentrations.", "contents": "Tryptophan fluorescence of (Na+ + K+)-ATPase as a tool for study of the enzyme mechanism. 1. The protein fluorescence intensity of (Na+ + K+)-ATPase is enhanced following binding of K+ at low concentrations. The properties of the response suggest that one or a few tryptophan residues are affected by a conformational transition between the K-bound form E2 . (K) and a Na-bound form E1 . Na. 2. The rate of the conformational transition E2 . (K) leads to E . Na has been measured with a stopped-flow fluorimeter by exploiting the difference in fluorescence of the two states. In the absence of ATP the rate is very slow, but it is greatly accelerated by binding of ATP to a low affinity site. 3. Transient changes in tryptophan fluorescence accompany hydrolysis of ATP at low concentrations, in media containing Mg2+, Na+ and K+. The fluorescence response reflects interconversion between the initial enzyme conformation, E1 . Na and the steady-state turnover intermediate E2 . (K). 4. The phosphorylated intermediate, E2P can be detected by a fluorescence increase accompanying hydrolysis of ATP in media containing Mg2+ and Na+ but no K+. 5. The conformational states and reaction mechanism of the (Na+ + K+)-ATPase are discussed in the light of this work. The results permit a comparison of the behaviour of the enzyme at both low and high nucleotide concentrations."}
{"id": "PMID:214133", "title": "Studies on the properties of triphosphoinositide phosphomonoesterase and phosphodiesterase of rabbit iris smooth muscle.", "content": "The rabbit iris smooth muscle has been shown to contain triphosphoinositide phosphomonoesterase (phosphatidyl-myo-inositol-4,5-bisphosphate phosphohydrolase, EC 3.1.3.36) and phosphodiesterase (triphosphoinositide inositoltrisphosphohydrolase, EC 3.1.4.11) activities. Under our experimental conditions about 77% of the phosphomonoesterase and 61% of the phosphodiesterase activities were localized in the particulate fraction. The kinetic properties of the enzymes in the microsomal fraction were examined. The enzyme preparation was specific to polyphosphoinositides; it did not attack phosphatidylinositol under the present assay condition. The effects of Ca2+ and Mg2+ were also studied. Although the microsomal enzymes did not require added divalent cations for their activities, both the phosphomonoesterase and phosphodiesterase were appreciably inhibited by 1 mM EDTA. Phosphodiesterase and phosphomonoesterase were stimulated by Ca2+ and Mg2+, respectively. The demonstration of triphosphoinositide phosphodiesterase in the iris muscle, coupled with the findings that this enzyme is activated by Ca2+ and is not influenced by acetylcholine add further support to our previous conclusion (J. Pharmacol. Exp. Ther. (1978) 204, 655--668; J. Neurochem. (1978) 30, 517--525) that an increased Ca2+ influx, following the interaction between the neurotransmitter and its receptor, could act to stimulate the phosphodiesterase, thus leading to increased triphosphoinositide breakdown and increased phosphatidic acid via increased diacylglycerol.", "contents": "Studies on the properties of triphosphoinositide phosphomonoesterase and phosphodiesterase of rabbit iris smooth muscle. The rabbit iris smooth muscle has been shown to contain triphosphoinositide phosphomonoesterase (phosphatidyl-myo-inositol-4,5-bisphosphate phosphohydrolase, EC 3.1.3.36) and phosphodiesterase (triphosphoinositide inositoltrisphosphohydrolase, EC 3.1.4.11) activities. Under our experimental conditions about 77% of the phosphomonoesterase and 61% of the phosphodiesterase activities were localized in the particulate fraction. The kinetic properties of the enzymes in the microsomal fraction were examined. The enzyme preparation was specific to polyphosphoinositides; it did not attack phosphatidylinositol under the present assay condition. The effects of Ca2+ and Mg2+ were also studied. Although the microsomal enzymes did not require added divalent cations for their activities, both the phosphomonoesterase and phosphodiesterase were appreciably inhibited by 1 mM EDTA. Phosphodiesterase and phosphomonoesterase were stimulated by Ca2+ and Mg2+, respectively. The demonstration of triphosphoinositide phosphodiesterase in the iris muscle, coupled with the findings that this enzyme is activated by Ca2+ and is not influenced by acetylcholine add further support to our previous conclusion (J. Pharmacol. Exp. Ther. (1978) 204, 655--668; J. Neurochem. (1978) 30, 517--525) that an increased Ca2+ influx, following the interaction between the neurotransmitter and its receptor, could act to stimulate the phosphodiesterase, thus leading to increased triphosphoinositide breakdown and increased phosphatidic acid via increased diacylglycerol."}
{"id": "PMID:214134", "title": "The oscillating peroxidase-oxidase reaction in an open system. Analysis of the reaction mechanism.", "content": "1. The oscillations in the peroxidase-oxidase reaction in an open system with NADH as the hydrogen donor are caused by the reaction starting and stopping at critical concentrations of the substrates O2 and NADH. The existence of such critical concentrations is typical of branched chain reactions. 2. The critical concentrations of O2 and NADH that determine the initiation of the reaction are mutually dependent. 3. The branching reactions that determine these critical concentrations involve compounds I and II. 4. Superoxide may be involved in the branching reactions by reacting with NADH and ferriperoxidase. At pH 5.1 the rate constant for the latter reaction is determined as 1.5 . 10(5) M-1 . s-1, whereas for the former reaction only an upper limit for the rate constant of 3.5 . 10(4) M-1 . s-1 could be estimated. These relatively low rate constants suggest that alternative branching reactions may also be involved.", "contents": "The oscillating peroxidase-oxidase reaction in an open system. Analysis of the reaction mechanism. 1. The oscillations in the peroxidase-oxidase reaction in an open system with NADH as the hydrogen donor are caused by the reaction starting and stopping at critical concentrations of the substrates O2 and NADH. The existence of such critical concentrations is typical of branched chain reactions. 2. The critical concentrations of O2 and NADH that determine the initiation of the reaction are mutually dependent. 3. The branching reactions that determine these critical concentrations involve compounds I and II. 4. Superoxide may be involved in the branching reactions by reacting with NADH and ferriperoxidase. At pH 5.1 the rate constant for the latter reaction is determined as 1.5 . 10(5) M-1 . s-1, whereas for the former reaction only an upper limit for the rate constant of 3.5 . 10(4) M-1 . s-1 could be estimated. These relatively low rate constants suggest that alternative branching reactions may also be involved."}
{"id": "PMID:214135", "title": "Kinetics of enzyme-coenzyme interactions by NMR spectroscopy.", "content": "The kinetics for the binding of coenzymes to H4 and M4 lactate dehydrogenase from chicken were investigated by nuclear magnetic resonance spectroscopy. With detailed computer analysis, some kinetic parameters were extracted from the chemical shifts and the linewidth of the observed coenzyme resonances at various enzyme/coenzyme ratios and temperatures. The results of the analysis indicated that the dissociation rates of coenzymes from the enzyme/coenzyme complexes are slower with the H4 isozyme than those involving the M4 isozyme. The lifetimes for the NAD+-enzyme complexes are on the order of 1 msec while those for the NADH-enzyme complexes are on the order of 10 ms (at room temperature). Much shorter transverse relaxation times of the coenzyme resonances were observed in NADH-enzyme complexes than those in the NAD+-enzyme complexes. The calculated kinetic constants are in good agreement with the previous studies by stopped-flow and temperature jump methods. A generalized NMR kinetic treatment for the binding of small molecules to a macromolecule is presented.", "contents": "Kinetics of enzyme-coenzyme interactions by NMR spectroscopy. The kinetics for the binding of coenzymes to H4 and M4 lactate dehydrogenase from chicken were investigated by nuclear magnetic resonance spectroscopy. With detailed computer analysis, some kinetic parameters were extracted from the chemical shifts and the linewidth of the observed coenzyme resonances at various enzyme/coenzyme ratios and temperatures. The results of the analysis indicated that the dissociation rates of coenzymes from the enzyme/coenzyme complexes are slower with the H4 isozyme than those involving the M4 isozyme. The lifetimes for the NAD+-enzyme complexes are on the order of 1 msec while those for the NADH-enzyme complexes are on the order of 10 ms (at room temperature). Much shorter transverse relaxation times of the coenzyme resonances were observed in NADH-enzyme complexes than those in the NAD+-enzyme complexes. The calculated kinetic constants are in good agreement with the previous studies by stopped-flow and temperature jump methods. A generalized NMR kinetic treatment for the binding of small molecules to a macromolecule is presented."}
{"id": "PMID:214136", "title": "Purification and properties of bovine liver lysosomal adenosine 5'-phosphosulphate sulphohydrolase. A non-specific enzyme with pyrophosphatase and phosphodiesterase activities.", "content": "Bovine liver lysosomal adenosine 5'-phosphosulphate sulphohydrolase (EC 3.6.2.1) was purified to apparent homogeneity. The molecular weight of the enzyme was 53 000 by sodium dodecyl sulphate polyacrylamide gel electrophoresis and 56 000 by BioGel P-150 gel filtration. The substrate specificity of the enzyme was studied. The several substrates towards which the enzyme preparation showed high activity were used to establish that a single enzyme was responsible for the different activities. This multiple specificity provides a possible explanation of the physiological role of lysosomal adenosine 5'-phosphosulphate sulphohydrolase.", "contents": "Purification and properties of bovine liver lysosomal adenosine 5'-phosphosulphate sulphohydrolase. A non-specific enzyme with pyrophosphatase and phosphodiesterase activities. Bovine liver lysosomal adenosine 5'-phosphosulphate sulphohydrolase (EC 3.6.2.1) was purified to apparent homogeneity. The molecular weight of the enzyme was 53 000 by sodium dodecyl sulphate polyacrylamide gel electrophoresis and 56 000 by BioGel P-150 gel filtration. The substrate specificity of the enzyme was studied. The several substrates towards which the enzyme preparation showed high activity were used to establish that a single enzyme was responsible for the different activities. This multiple specificity provides a possible explanation of the physiological role of lysosomal adenosine 5'-phosphosulphate sulphohydrolase."}
{"id": "PMID:214137", "title": "The effect of myo-inositol deficiency on lipid metabolism in rats. III. The mechanism of an enhancement in lipolysis due to myo-inositol deficiency in rats.", "content": "myo-Inositol deficiency in rats produced an overaccumulation of triacylglycerols in the liver due to stimulated lipolysis in the adipose tissue (Hayashi, E., Maeda, T. and Tomita, T. (1974) Biochim. Biophys. Acta 360, 134--155). The mechanism of the enhancement in lipolysis has now been investigated. The lipolytic response to adrenalin, corticotropin and insulin of the epididymal adipose tissue did not change due to the deficiency, but hormone-sensitive lipase activity, plasma adrenalin level and blood pressure were higher in the deficient rats. Adrenalectomy had no influence, but administration of sympathetic nervous blockers (reserpine, hexamethonium and bupranolol) inhibited the liver lipid deposition and an increase of serum free fatty acids in the deficient rats. These results indicate that the enhancement in lipolysis is mediated by an excitation of sympathetic nerve terminals innervating in the adipose tissues.", "contents": "The effect of myo-inositol deficiency on lipid metabolism in rats. III. The mechanism of an enhancement in lipolysis due to myo-inositol deficiency in rats. myo-Inositol deficiency in rats produced an overaccumulation of triacylglycerols in the liver due to stimulated lipolysis in the adipose tissue (Hayashi, E., Maeda, T. and Tomita, T. (1974) Biochim. Biophys. Acta 360, 134--155). The mechanism of the enhancement in lipolysis has now been investigated. The lipolytic response to adrenalin, corticotropin and insulin of the epididymal adipose tissue did not change due to the deficiency, but hormone-sensitive lipase activity, plasma adrenalin level and blood pressure were higher in the deficient rats. Adrenalectomy had no influence, but administration of sympathetic nervous blockers (reserpine, hexamethonium and bupranolol) inhibited the liver lipid deposition and an increase of serum free fatty acids in the deficient rats. These results indicate that the enhancement in lipolysis is mediated by an excitation of sympathetic nerve terminals innervating in the adipose tissues."}
{"id": "PMID:214138", "title": "Magnesium-dependent sphingomyelinase of infantile brain. Effect of detergents and a heat-stable factor.", "content": "The properties of the Mg2+-dependent sphingomyelinase, whose pH optimum is between 7 and 8, were investigated using post-mortem infantile brain. The enzyme could be extracted with 0.2% Triton X-100 and remained soluble when centrifuged at 170,000 X g. Subsequent removal of the detergent with SM2-Biobeads resulted in resedimentation of the enzyme at 80,000 X g. A detergent was needed for assaying enzymatic activity; either Triton X-100 or bile salts could be used. With increasing concentrations of detergent, the rates of hydrolysis of sphinomyelin increased, reached an optimum and then decreased, suggesting inhibition of the enzyme. The concentrations of detergent which resulted in optimal reaction rates were directly related to the protein concentration of the enzymatic preparation. A heat-stable factor which counteracts inhibition by the above detergents is present in brain as well as several other tissues. A lipid extract of the enzymatic preparation, or several purified lipids could not mimic the effect of the heat-stable factor. The interrelationship between enzyme, detergent and the heat-stable factor was investigated.", "contents": "Magnesium-dependent sphingomyelinase of infantile brain. Effect of detergents and a heat-stable factor. The properties of the Mg2+-dependent sphingomyelinase, whose pH optimum is between 7 and 8, were investigated using post-mortem infantile brain. The enzyme could be extracted with 0.2% Triton X-100 and remained soluble when centrifuged at 170,000 X g. Subsequent removal of the detergent with SM2-Biobeads resulted in resedimentation of the enzyme at 80,000 X g. A detergent was needed for assaying enzymatic activity; either Triton X-100 or bile salts could be used. With increasing concentrations of detergent, the rates of hydrolysis of sphinomyelin increased, reached an optimum and then decreased, suggesting inhibition of the enzyme. The concentrations of detergent which resulted in optimal reaction rates were directly related to the protein concentration of the enzymatic preparation. A heat-stable factor which counteracts inhibition by the above detergents is present in brain as well as several other tissues. A lipid extract of the enzymatic preparation, or several purified lipids could not mimic the effect of the heat-stable factor. The interrelationship between enzyme, detergent and the heat-stable factor was investigated."}
{"id": "PMID:214139", "title": "The activity of an esterified cholesterol transferring factor in human and rat serum.", "content": "In incubations containing mixtures of lipoproteins isolated either from humans or from rats, the addition of human lipoproteins-free serum (the dialysed 1.25 g/ml infranatant solution) was more than five times more effective than that of the rat in promoting the transfer of esterified [3H]cholesterol from high density lipoproteins to very low density lipoproteins, regardless of the species origin of the lipoproteins, implying the existence of an esterified cholesterol transferring factor of much greater activity in human than in rat serum.", "contents": "The activity of an esterified cholesterol transferring factor in human and rat serum. In incubations containing mixtures of lipoproteins isolated either from humans or from rats, the addition of human lipoproteins-free serum (the dialysed 1.25 g/ml infranatant solution) was more than five times more effective than that of the rat in promoting the transfer of esterified [3H]cholesterol from high density lipoproteins to very low density lipoproteins, regardless of the species origin of the lipoproteins, implying the existence of an esterified cholesterol transferring factor of much greater activity in human than in rat serum."}
{"id": "PMID:214140", "title": "Further characterization of human erythrocyte superoxide dismutase.", "content": "1. A simplified procedure for the preparation of highly purified human superoxide dismutase from erythrocytes was developed which avoided extremes of pH and ionic strength and the use of organic solvents; the properties of human and bovine proteins, prepared by the method, were compared. 2. Using the two dimensional electrophoretic procedure of O'Farrell, the human superoxide dismutase was found to consist of a single type of polypeptide. 3. The human protein was found to have a total of eight half-cystine residues per mole of protein, compared to six such residues for the bovine protein. The human protein has two sulfhydryl groups which are reactive toward mercurials when dissolved in 1M guanidine-hydrochloride and approximately 3 reactive sulfhydrls when the protein is dissolved in 6 M guanidine hydrochloride. The distribution of the eight sulfur atoms appears to consist of four involved in disulfide linkages, two deeply buried within the molecule and unreactive except under strongly denaturing conditions, and two which are reactive under mildly denaturing conditions. No zero-valent sulfur was found. 4. The visible optical absorption, the visible circular dichroism, and the electron paramagnetic resonance spectra are essentially identical with those of the bovine protein. No unusual absorbance was found at 330 nm. The near ultraviolet spectrum is different from that of the bovine protein, and this appears to be due to differing amino acid compositions. 5. Two fractions of superoxide dismutase activity were observed during chromatography of partially purified solutions on diethylaminoethyl-cellulose. The minor, less mobile form, was found to revert to the less mobile species on aging; the reverse process was not observed to occur. The minor component was found to contain equimolar amounts of Zn and Cu and to have a specific dismutase activity somewhat higher than that of the purified major fraction.", "contents": "Further characterization of human erythrocyte superoxide dismutase. 1. A simplified procedure for the preparation of highly purified human superoxide dismutase from erythrocytes was developed which avoided extremes of pH and ionic strength and the use of organic solvents; the properties of human and bovine proteins, prepared by the method, were compared. 2. Using the two dimensional electrophoretic procedure of O'Farrell, the human superoxide dismutase was found to consist of a single type of polypeptide. 3. The human protein was found to have a total of eight half-cystine residues per mole of protein, compared to six such residues for the bovine protein. The human protein has two sulfhydryl groups which are reactive toward mercurials when dissolved in 1M guanidine-hydrochloride and approximately 3 reactive sulfhydrls when the protein is dissolved in 6 M guanidine hydrochloride. The distribution of the eight sulfur atoms appears to consist of four involved in disulfide linkages, two deeply buried within the molecule and unreactive except under strongly denaturing conditions, and two which are reactive under mildly denaturing conditions. No zero-valent sulfur was found. 4. The visible optical absorption, the visible circular dichroism, and the electron paramagnetic resonance spectra are essentially identical with those of the bovine protein. No unusual absorbance was found at 330 nm. The near ultraviolet spectrum is different from that of the bovine protein, and this appears to be due to differing amino acid compositions. 5. Two fractions of superoxide dismutase activity were observed during chromatography of partially purified solutions on diethylaminoethyl-cellulose. The minor, less mobile form, was found to revert to the less mobile species on aging; the reverse process was not observed to occur. The minor component was found to contain equimolar amounts of Zn and Cu and to have a specific dismutase activity somewhat higher than that of the purified major fraction."}
{"id": "PMID:214141", "title": "The activation by Ca2+ of platelet phospholipase A2. Effects of dibutyryl cyclic adenosine monophosphate and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate.", "content": "Thrombin-induced release of arachidonic acid from human platelet phosphatidylcholine is found to be more than 90% impaired by incubation of platelets with 1 mM dibutyryl cyclic adenosine monophosphate (Bt2 cyclic AMP) or with 0.6 mM 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), an intracellular calcium antagonist. Incorporation of arachidonic acid into platelet phospholipids is not enhanced by Bt2 cyclic AMP. The addition of external Ca2+ to thrombin-treated platelets incubated with Bt2 cyclic AMP or TMB-8 does not counteract the observed inhibition. However, when divalent cation ionophore A23187 is employed as an activating agent, much less inhibition is produced by Bt2 cyclic AMP or TMB-8. The inhibition which does result can be overcome by added Ca2+. Inhibition of arachidonic acid liberation by Bt2 cyclic AMP, but not by TMB-8, can be overcome by high concentrations of A23187. When Mg2+ is substituted for Ca2+, ionophore-induced release of arachidonic acid from phosphatidylcholine of inhibitor-free controls is depressed and inhibition by Bt2 cyclic AMP is slightly enhanced. The phospholipase A2 activity of platelet lysates is increased by the presence of added Ca2+, however, the addition of either A23187 or Bt2 cyclic AMP is without effect on this activity. We suggest that Bt2 cyclic AMP may promote a compartmentalization of Ca2+, thereby inhibiting phospholipase A activity. The compartmentalization may be overcome by ionophore. By contrast, TMB-8 may immobilize platelet Ca2+ stores in situ or restrict access of Ca2+ to phospholipase A in a manner not susceptible to reversal by high concentrations of ionophore.", "contents": "The activation by Ca2+ of platelet phospholipase A2. Effects of dibutyryl cyclic adenosine monophosphate and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate. Thrombin-induced release of arachidonic acid from human platelet phosphatidylcholine is found to be more than 90% impaired by incubation of platelets with 1 mM dibutyryl cyclic adenosine monophosphate (Bt2 cyclic AMP) or with 0.6 mM 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), an intracellular calcium antagonist. Incorporation of arachidonic acid into platelet phospholipids is not enhanced by Bt2 cyclic AMP. The addition of external Ca2+ to thrombin-treated platelets incubated with Bt2 cyclic AMP or TMB-8 does not counteract the observed inhibition. However, when divalent cation ionophore A23187 is employed as an activating agent, much less inhibition is produced by Bt2 cyclic AMP or TMB-8. The inhibition which does result can be overcome by added Ca2+. Inhibition of arachidonic acid liberation by Bt2 cyclic AMP, but not by TMB-8, can be overcome by high concentrations of A23187. When Mg2+ is substituted for Ca2+, ionophore-induced release of arachidonic acid from phosphatidylcholine of inhibitor-free controls is depressed and inhibition by Bt2 cyclic AMP is slightly enhanced. The phospholipase A2 activity of platelet lysates is increased by the presence of added Ca2+, however, the addition of either A23187 or Bt2 cyclic AMP is without effect on this activity. We suggest that Bt2 cyclic AMP may promote a compartmentalization of Ca2+, thereby inhibiting phospholipase A activity. The compartmentalization may be overcome by ionophore. By contrast, TMB-8 may immobilize platelet Ca2+ stores in situ or restrict access of Ca2+ to phospholipase A in a manner not susceptible to reversal by high concentrations of ionophore."}
{"id": "PMID:214142", "title": "A two-step enzymatic formation of a glucoprotein in potato tuber.", "content": "Evidence is presented on the occurrence of a two-step mechanism for the synthesis of protein bound glucan in a potato tuber particulate preparation. Experiments carried out with a differently labeled sugar donor for each step enabled the isolation of a double-labeled glucoprotein. Smith periodate degradation of the product confirmed this hypothesis.", "contents": "A two-step enzymatic formation of a glucoprotein in potato tuber. Evidence is presented on the occurrence of a two-step mechanism for the synthesis of protein bound glucan in a potato tuber particulate preparation. Experiments carried out with a differently labeled sugar donor for each step enabled the isolation of a double-labeled glucoprotein. Smith periodate degradation of the product confirmed this hypothesis."}
{"id": "PMID:214143", "title": "Effects of calcium and chelating agents on the ability of various agonists to increase cyclic GMP in pancreatic acinar cells.", "content": "In dispersed acinar cells from guinea pig pancreas we found that chelating extracellular calcium with EDTA did not alter cellular cyclic GMP but caused a 50% reduction in the increase in cyclic GMP caused by the synthetic C-terminal octapeptide of porcine cholecystokinin (cholecystokinin octapeptide). This effect was maximal within 2 min and preincubating the cells with EDTA for as long as 30 min caused no further reduction in the action of cholecystokinin octapeptide. In acinar cells preincubated without calcium, adding calcium caused a time dependent increase in the action of cholecystokinin octapeptide and this increase was maximal after 10 min of incubation. An effect of extracellular calcium on the action of cholecystokinin octapeptide could be detected with 0.5 mM calcium and was maximal with 2.0 mM calcium. Magnesium alone or with calcium did not alter the action of cholecystokinin octapeptide. Extracellular calcium did not alter the time course or the configuration of the dose vs. response curve for the action of cholecystokinin octapeptide on cellular cyclic GMP. Low concentrations of EGTA (0.1 mM) decreased the effect of cholecystokinin octapeptide on cellular cyclic GMP to the same extent as did EDTA or preincubating acinar cells without calcium. Increasing EGTA above 0.1 mM caused progressive augmentation of the action of cholecystokinin octapeptide on cellular cyclic GMP and this augmentation did not require extracellular calcium or magnesium. Results similar to those obtained with cholecystokinin octapeptide were also obtained with bombesin, carbamylcholine, litorin and eledoisin. In contrast, the action of sodium nitroprusside on cyclic GMP in pancreatic acinar cells was not altered by adding EDTA or EGTA. These results indicate that the ability of extracellular calcium to influence the action of cholecystokinin octapeptide and other agents on cyclic GMP results from changes in cellular calcium and not from effects of extracellular calcium per se. The action of low concentrations of EGTA on the increase in cyclic GMP caused by various agents reflects the ability of EGTA to chelate extracellular calcium. The actions of high concentrations of EGTA were independent of extracellular calcium or magnesium and appear to reflect a direct action of EGTA on pancreatic acinar cells.", "contents": "Effects of calcium and chelating agents on the ability of various agonists to increase cyclic GMP in pancreatic acinar cells. In dispersed acinar cells from guinea pig pancreas we found that chelating extracellular calcium with EDTA did not alter cellular cyclic GMP but caused a 50% reduction in the increase in cyclic GMP caused by the synthetic C-terminal octapeptide of porcine cholecystokinin (cholecystokinin octapeptide). This effect was maximal within 2 min and preincubating the cells with EDTA for as long as 30 min caused no further reduction in the action of cholecystokinin octapeptide. In acinar cells preincubated without calcium, adding calcium caused a time dependent increase in the action of cholecystokinin octapeptide and this increase was maximal after 10 min of incubation. An effect of extracellular calcium on the action of cholecystokinin octapeptide could be detected with 0.5 mM calcium and was maximal with 2.0 mM calcium. Magnesium alone or with calcium did not alter the action of cholecystokinin octapeptide. Extracellular calcium did not alter the time course or the configuration of the dose vs. response curve for the action of cholecystokinin octapeptide on cellular cyclic GMP. Low concentrations of EGTA (0.1 mM) decreased the effect of cholecystokinin octapeptide on cellular cyclic GMP to the same extent as did EDTA or preincubating acinar cells without calcium. Increasing EGTA above 0.1 mM caused progressive augmentation of the action of cholecystokinin octapeptide on cellular cyclic GMP and this augmentation did not require extracellular calcium or magnesium. Results similar to those obtained with cholecystokinin octapeptide were also obtained with bombesin, carbamylcholine, litorin and eledoisin. In contrast, the action of sodium nitroprusside on cyclic GMP in pancreatic acinar cells was not altered by adding EDTA or EGTA. These results indicate that the ability of extracellular calcium to influence the action of cholecystokinin octapeptide and other agents on cyclic GMP results from changes in cellular calcium and not from effects of extracellular calcium per se. The action of low concentrations of EGTA on the increase in cyclic GMP caused by various agents reflects the ability of EGTA to chelate extracellular calcium. The actions of high concentrations of EGTA were independent of extracellular calcium or magnesium and appear to reflect a direct action of EGTA on pancreatic acinar cells."}
{"id": "PMID:214144", "title": "The effect of gamma radiation and neocarzinostatin on NAD and ATP levels in mouse leukaemia cells.", "content": "When mouse leukemia cells are treated with gamma-radiation or neocarzinostatin the intracellular NAD and ATP levels fall rapidly. We have shown that the ATP response is a consequence of the decreased NAD level. We suggest that this low NAD level results in decreased glycolytic activity and that there is a subsequent accumulation of phosphorylated sugars associated with the fall in ATP. Under these extreme conditions, therefore, the NAD level probably regulates the rate of glycolysis in cells which are utilising a rapidly metabolisable sugar as their energy source.", "contents": "The effect of gamma radiation and neocarzinostatin on NAD and ATP levels in mouse leukaemia cells. When mouse leukemia cells are treated with gamma-radiation or neocarzinostatin the intracellular NAD and ATP levels fall rapidly. We have shown that the ATP response is a consequence of the decreased NAD level. We suggest that this low NAD level results in decreased glycolytic activity and that there is a subsequent accumulation of phosphorylated sugars associated with the fall in ATP. Under these extreme conditions, therefore, the NAD level probably regulates the rate of glycolysis in cells which are utilising a rapidly metabolisable sugar as their energy source."}
{"id": "PMID:214145", "title": "A possible role for guanosine 3',5'-monophosphate in the stimulus-secretion coupling in exocrine pancreas.", "content": "Carbamylcholine, caerulein and cholecystokinin octapeptide rapidly increased the cyclic GMP concentration and amylase secretion in isolated guinea pig pancreatic slices. The cyclic GMP concentration was increased eight-fold over the basal concentration in 30 s, with concomitant increase in the rate of amylase secretion. The tissue concentration of cyclic GMP then rapidly declined to a plateau value of approx. 16% of the peak level within 10 min and was maintained at that concentration for the duration of the experiment. We have shown earlier (Kapoor, CL. and Krishna, G. (1977) Science 196, 1003--1005) that the decrease of tissue cyclic GMP was due mainly to the secretion of cyclic GMP into the medium. The cyclic AMP concentration in the tissue was not changed, nor was it secreted into the medium. There was a correlation between the concentration response to various agents for the increase in cyclic GMP concentration and amylase secretion in pancreatic slices. Carbamylcholine increased both the cyclic GMP concentration and amylase secretion; the half-maximal effect was achieved at 1.5 micrometer concentration. Caerulein and cholecystokinin octapeptide were 5000 times more potent than carbamylcholine in increasing cyclic GMP concentration and amylase secretion; the half-maximal effect was achieved at 0.3 nM concentration. Atropine, which completely inhibited the increase in cyclic GMP and amylase secretion induced by carbamylcholine, did not block the effects of caerulein or cholecystokinin octapeptide. These results suggest that various secretagogues induced amylase secretion by increasing the cyclic GMP concentration, but the mechanism by which cyclic GMP caused amylase secretion remains to be elucidated.", "contents": "A possible role for guanosine 3',5'-monophosphate in the stimulus-secretion coupling in exocrine pancreas. Carbamylcholine, caerulein and cholecystokinin octapeptide rapidly increased the cyclic GMP concentration and amylase secretion in isolated guinea pig pancreatic slices. The cyclic GMP concentration was increased eight-fold over the basal concentration in 30 s, with concomitant increase in the rate of amylase secretion. The tissue concentration of cyclic GMP then rapidly declined to a plateau value of approx. 16% of the peak level within 10 min and was maintained at that concentration for the duration of the experiment. We have shown earlier (Kapoor, CL. and Krishna, G. (1977) Science 196, 1003--1005) that the decrease of tissue cyclic GMP was due mainly to the secretion of cyclic GMP into the medium. The cyclic AMP concentration in the tissue was not changed, nor was it secreted into the medium. There was a correlation between the concentration response to various agents for the increase in cyclic GMP concentration and amylase secretion in pancreatic slices. Carbamylcholine increased both the cyclic GMP concentration and amylase secretion; the half-maximal effect was achieved at 1.5 micrometer concentration. Caerulein and cholecystokinin octapeptide were 5000 times more potent than carbamylcholine in increasing cyclic GMP concentration and amylase secretion; the half-maximal effect was achieved at 0.3 nM concentration. Atropine, which completely inhibited the increase in cyclic GMP and amylase secretion induced by carbamylcholine, did not block the effects of caerulein or cholecystokinin octapeptide. These results suggest that various secretagogues induced amylase secretion by increasing the cyclic GMP concentration, but the mechanism by which cyclic GMP caused amylase secretion remains to be elucidated."}
{"id": "PMID:214146", "title": "Change of coupling system of receptor-adenylate cyclase induced by epinephrine and GTP in plasma membranes of rat liver.", "content": "1. The binding of [3H]epinephrine to plasma membranes was affected (temporary release of bound epinephrine and characteristic retardation of epinephrine binding) not only by GTP but also by dGTP and guanylylimidodiphosphate, whereas the binding of [3H]dihydroalprenolol was not affected by GTP. GTP affected the binding of [3H]epinephrine in the presence of alpha-antagonists, but not in the presence of beta-antagonists, suggesting that the GTP effects are specific to beta-agonists and beta-receptors. 2. The half-maximal release of bound [3H]epinephrine was found at 8.8 . 10(-6) M GTP in the absence of ATP, whereas it was found at 1.6 . 10(-6) M GTP in the presence of 0.3 mM ATP in coincidence with the half-maximal activation of adenylate cyclase by GTP in the presence of 0.3 mM ATP (as measured at 30 s of incubation). 3. In the presence of 4 . 10(-5) M GTP, adenylate cyclase activity as measured at 30 s of incubation (State I) tended to increase with epinephrine concentration, showing no saturation tendency even at 1 . 10(-4) M epinephrine. The activity of State II, which is established at 4 min of incubation, was much lower than that of State I but was found to reach a plateau as the epinephrine concentration increased, showing half-maximal activation at an epinephrine concentration between 2 . 10(-6) and 2 . 10(-7) M. 4. Apparent kinetic parameters (Km and V) for State I as assayed at 30 s of incubation suggested that GTP alone may increase V slightly, whereas epinephrine plus GTP may increase the V to a further extent and simultaneously decrease the Km. 5. Adenylate cyclase of plasma membranes pretreated with epinephrine plus GTP was stimulated by GTP alone similarly to untreated membranes, but it was no longer responsive to the synergistic activation by epinephrine plus GTP. Accordingly, the binding of [3H]epinephrine to the pretreated plasma membranes was no longer affected by GTP. 6. The results of the present study seem to support the idea that the most active and coherently coupling state (State I) of the beta-receptor-adenylate cyclase system generated in the presence of epinephrine plus GTP is very labile and degenerates before reaching equilibrium. In turn, State II, in which the coherently coupling mechanism is largely impaired, seems to be established in due time. The characteristic biphasic kinetics of [3H]epinephrine binding in the presence of GTP seem to be related to the above change occurring in the beta-receptor-adenylate cyclase system.", "contents": "Change of coupling system of receptor-adenylate cyclase induced by epinephrine and GTP in plasma membranes of rat liver. 1. The binding of [3H]epinephrine to plasma membranes was affected (temporary release of bound epinephrine and characteristic retardation of epinephrine binding) not only by GTP but also by dGTP and guanylylimidodiphosphate, whereas the binding of [3H]dihydroalprenolol was not affected by GTP. GTP affected the binding of [3H]epinephrine in the presence of alpha-antagonists, but not in the presence of beta-antagonists, suggesting that the GTP effects are specific to beta-agonists and beta-receptors. 2. The half-maximal release of bound [3H]epinephrine was found at 8.8 . 10(-6) M GTP in the absence of ATP, whereas it was found at 1.6 . 10(-6) M GTP in the presence of 0.3 mM ATP in coincidence with the half-maximal activation of adenylate cyclase by GTP in the presence of 0.3 mM ATP (as measured at 30 s of incubation). 3. In the presence of 4 . 10(-5) M GTP, adenylate cyclase activity as measured at 30 s of incubation (State I) tended to increase with epinephrine concentration, showing no saturation tendency even at 1 . 10(-4) M epinephrine. The activity of State II, which is established at 4 min of incubation, was much lower than that of State I but was found to reach a plateau as the epinephrine concentration increased, showing half-maximal activation at an epinephrine concentration between 2 . 10(-6) and 2 . 10(-7) M. 4. Apparent kinetic parameters (Km and V) for State I as assayed at 30 s of incubation suggested that GTP alone may increase V slightly, whereas epinephrine plus GTP may increase the V to a further extent and simultaneously decrease the Km. 5. Adenylate cyclase of plasma membranes pretreated with epinephrine plus GTP was stimulated by GTP alone similarly to untreated membranes, but it was no longer responsive to the synergistic activation by epinephrine plus GTP. Accordingly, the binding of [3H]epinephrine to the pretreated plasma membranes was no longer affected by GTP. 6. The results of the present study seem to support the idea that the most active and coherently coupling state (State I) of the beta-receptor-adenylate cyclase system generated in the presence of epinephrine plus GTP is very labile and degenerates before reaching equilibrium. In turn, State II, in which the coherently coupling mechanism is largely impaired, seems to be established in due time. The characteristic biphasic kinetics of [3H]epinephrine binding in the presence of GTP seem to be related to the above change occurring in the beta-receptor-adenylate cyclase system."}
{"id": "PMID:214147", "title": "Separation of cyclic AMP and cyclic GMP from thymidine, electrolytes and polyvalent nucleotides in tissue samples.", "content": "Cyclic AMP and cyclic GMP can be separated from thymidine and its possible metabolites, electrolytes, and polyvalent nucleotides using columns of acidic alumina. Electrolytes and thymidine are not adsorbed on acidic alumina at pH 4.4 while cyclic nucleotides and polyvalent nucleotides are adsorbed at this pH. Cyclic AMP and cyclic GMP are eluted together from acidic alumina with 0.2 M ammonium formate (pH 6.0) and the polyvalent nucleotides remain adsorbed. The cyclic nucleotides are separated by chromatography on Dowex AG 1 X 8 resin. Recovery is 60--64% for cyclic AMP and cyclic GMP isolated from renal tissue samples. This methodology permits the separation of tritiated thymidine from cyclic nucleotides which are present in tissue preparations used in studies on the role of cyclic nucleotides in cellular growth.", "contents": "Separation of cyclic AMP and cyclic GMP from thymidine, electrolytes and polyvalent nucleotides in tissue samples. Cyclic AMP and cyclic GMP can be separated from thymidine and its possible metabolites, electrolytes, and polyvalent nucleotides using columns of acidic alumina. Electrolytes and thymidine are not adsorbed on acidic alumina at pH 4.4 while cyclic nucleotides and polyvalent nucleotides are adsorbed at this pH. Cyclic AMP and cyclic GMP are eluted together from acidic alumina with 0.2 M ammonium formate (pH 6.0) and the polyvalent nucleotides remain adsorbed. The cyclic nucleotides are separated by chromatography on Dowex AG 1 X 8 resin. Recovery is 60--64% for cyclic AMP and cyclic GMP isolated from renal tissue samples. This methodology permits the separation of tritiated thymidine from cyclic nucleotides which are present in tissue preparations used in studies on the role of cyclic nucleotides in cellular growth."}
{"id": "PMID:214149", "title": "Cyclic nucleotides and protein kinase systems in the developing chick retina and pigment epithelium.", "content": "During embryonic development of the chick neural retina, cyclic nucleotide levels are relatively uniform but rise abruptly at the time of hatching. The rise is thus not temporally correlated with features of morphological development such as outer segment elongation but rather with the onset of actual visual function. In the pigment epithelium, the cyclic AMP level declines throughout the embryonic period studied and does not rise at hatching. Cyclic GMP levels are much lower in both retina and pigment epithelium but rise several-fold at hatching. A binding protein is observed for cyclic AMP in the retina prior to outer segment development; cyclic GMP binding is considerably lower. Retinal ATP-kinase activity is high throughout the embryonic period studied and is stimulated up to 6-fold by 1 muM cyclic AMP and by 100 muM cyclic GMP. The major rise in GTP-kinase activity correlates temporally with photoreceptor outer segment development and may be involved intimately in the visual process.", "contents": "Cyclic nucleotides and protein kinase systems in the developing chick retina and pigment epithelium. During embryonic development of the chick neural retina, cyclic nucleotide levels are relatively uniform but rise abruptly at the time of hatching. The rise is thus not temporally correlated with features of morphological development such as outer segment elongation but rather with the onset of actual visual function. In the pigment epithelium, the cyclic AMP level declines throughout the embryonic period studied and does not rise at hatching. Cyclic GMP levels are much lower in both retina and pigment epithelium but rise several-fold at hatching. A binding protein is observed for cyclic AMP in the retina prior to outer segment development; cyclic GMP binding is considerably lower. Retinal ATP-kinase activity is high throughout the embryonic period studied and is stimulated up to 6-fold by 1 muM cyclic AMP and by 100 muM cyclic GMP. The major rise in GTP-kinase activity correlates temporally with photoreceptor outer segment development and may be involved intimately in the visual process."}
{"id": "PMID:214150", "title": "On the role of intra-adrenal unesterified cholesterol in the steroidogenic effect of corticotropin.", "content": "Since ACTH (corticotropin) increases intra-adrenal and intramitochondrial free cholesterol levels, the relative importance of these effects during ACTH-induced steroidogenesis was examined. Rats were treated in vivo with ACTH plus aminoglutethimide to increase free cholesterol (2--3-fold), and the latter was tested as a steroidogenic factor after removal of aminoglutethimide blockade and subsequent prolonged incubation of the cholesterol-rich adrenal sections in vitro. The increased free cholesterol served as a positive steroidogenic factor only during the early phase of the incubation when other ACTH-induced steroidogenic factors were operative. At later times of incubation, the increased free cholesterol did not, of itself, enhance steroidogenesis unless ACTH was added. These results suggest that the ACTH-induced enhancement of intraadrenal (and mitochondrial) free cholesterol may be important in determining the amount of steroids produced in response to a given ACTH stimulus, but another ACTH-induced factor is more important in initiating the steroidogenic process. This factor (? labile protein) appears to control a metabolic process which is distal to the mitochondrial uptake of free cholesterol.", "contents": "On the role of intra-adrenal unesterified cholesterol in the steroidogenic effect of corticotropin. Since ACTH (corticotropin) increases intra-adrenal and intramitochondrial free cholesterol levels, the relative importance of these effects during ACTH-induced steroidogenesis was examined. Rats were treated in vivo with ACTH plus aminoglutethimide to increase free cholesterol (2--3-fold), and the latter was tested as a steroidogenic factor after removal of aminoglutethimide blockade and subsequent prolonged incubation of the cholesterol-rich adrenal sections in vitro. The increased free cholesterol served as a positive steroidogenic factor only during the early phase of the incubation when other ACTH-induced steroidogenic factors were operative. At later times of incubation, the increased free cholesterol did not, of itself, enhance steroidogenesis unless ACTH was added. These results suggest that the ACTH-induced enhancement of intraadrenal (and mitochondrial) free cholesterol may be important in determining the amount of steroids produced in response to a given ACTH stimulus, but another ACTH-induced factor is more important in initiating the steroidogenic process. This factor (? labile protein) appears to control a metabolic process which is distal to the mitochondrial uptake of free cholesterol."}
{"id": "PMID:214151", "title": "The effect of periodate oxidation and alpha-mannosidase treatment on Dolichos biflorus lectin.", "content": "The effects of periodate oxidation and alpha-mannosidase treatment of the Dolichos biflorus lectin were determined. Destruction by periodate of 16% of the mannose residues of the lectin had no effect on its ability to agglutinate type A erythrocytes, precipitate blood group A + H substance or to be precipitated by concanavalin A. Removal of up to 40% of the mannose by either periodate or alpha-mannosidase rendered the lectin nonprecipitable by concanavalin A. The lectin treated by alpha-mannosidase retained its ability to agglutinate erythrocytes and precipitate blood group A + H substance, but the lectin treated with periodate lost most of its activity. The results suggest that the complete integrity of the carbohydrate unit of the lectin is not necessary for its activity and that the periodate may be affecting the protein portion of the molecule as well as its carbohydrate residues. No conversion of form A to form B of the lectin was observed with either periodate oxidation or alpha-mannosidase treatment.", "contents": "The effect of periodate oxidation and alpha-mannosidase treatment on Dolichos biflorus lectin. The effects of periodate oxidation and alpha-mannosidase treatment of the Dolichos biflorus lectin were determined. Destruction by periodate of 16% of the mannose residues of the lectin had no effect on its ability to agglutinate type A erythrocytes, precipitate blood group A + H substance or to be precipitated by concanavalin A. Removal of up to 40% of the mannose by either periodate or alpha-mannosidase rendered the lectin nonprecipitable by concanavalin A. The lectin treated by alpha-mannosidase retained its ability to agglutinate erythrocytes and precipitate blood group A + H substance, but the lectin treated with periodate lost most of its activity. The results suggest that the complete integrity of the carbohydrate unit of the lectin is not necessary for its activity and that the periodate may be affecting the protein portion of the molecule as well as its carbohydrate residues. No conversion of form A to form B of the lectin was observed with either periodate oxidation or alpha-mannosidase treatment."}
{"id": "PMID:214152", "title": "Evaluation of the negative cooperativity model for fat cell beta-adrenergic receptors.", "content": "Cooperative site-to-site interactions among beta-adrenergic receptors of fat cell membranes are probed with the potent beta-adrenergic antagonist (-)-[3H]dihydroalprenolol according to the kinetic method of De Meyts et al. (De Meyts, P., Roth, J., Neville, Jr., D.M., Gavin, III, J.R., and Lesniak, M.A. (1973) Biochem. Biophys. Res. Commun. 55, 154--161). Dissociation of specific (-)-[3H]dihydroalprenolol binding from fat cell membranes following a 100-fold dilution was rapid at 37 degrees C; only 40% of the initial equilibrium binding remained 30 s after dilution. Dissociation of (-)-[3H]dihydroalprenolol bound under conditions yielding approximately 20% initial occupancy was performed in the absence and in the presence of a large molar excess of beta-adrenergic agonist ((-)-isoproterenol) or beta-adrenergic antagonist ((-)-alprenolol or (-)-propanalol). Neither agonists nor antagonists influenced the rate of (-)-[3H]dihydroalprenolol dissociation from fat cell membranes performed at 4, 22 or 37 degrees C. Although analysis of the steady-state binding of (-)-[3H]dihydroalprenolol to fat cell membranes yields Hill coefficients, nH, less than 1.0, the present study indicates that these fat cell beta-adrenergic receptors display no cooperative site-to-site interactions.", "contents": "Evaluation of the negative cooperativity model for fat cell beta-adrenergic receptors. Cooperative site-to-site interactions among beta-adrenergic receptors of fat cell membranes are probed with the potent beta-adrenergic antagonist (-)-[3H]dihydroalprenolol according to the kinetic method of De Meyts et al. (De Meyts, P., Roth, J., Neville, Jr., D.M., Gavin, III, J.R., and Lesniak, M.A. (1973) Biochem. Biophys. Res. Commun. 55, 154--161). Dissociation of specific (-)-[3H]dihydroalprenolol binding from fat cell membranes following a 100-fold dilution was rapid at 37 degrees C; only 40% of the initial equilibrium binding remained 30 s after dilution. Dissociation of (-)-[3H]dihydroalprenolol bound under conditions yielding approximately 20% initial occupancy was performed in the absence and in the presence of a large molar excess of beta-adrenergic agonist ((-)-isoproterenol) or beta-adrenergic antagonist ((-)-alprenolol or (-)-propanalol). Neither agonists nor antagonists influenced the rate of (-)-[3H]dihydroalprenolol dissociation from fat cell membranes performed at 4, 22 or 37 degrees C. Although analysis of the steady-state binding of (-)-[3H]dihydroalprenolol to fat cell membranes yields Hill coefficients, nH, less than 1.0, the present study indicates that these fat cell beta-adrenergic receptors display no cooperative site-to-site interactions."}
{"id": "PMID:214153", "title": "Effects of part sequences of human growth hormone on in vivo hepatic glycogen metabolism in the rat.", "content": "Acute effects of two part sequences of human growth hormone on the in vivo activity levels of hepatic glycogen synthase and glycogen phosphorylase were examined. The peptide corresponding to residues 6 to 13 of the hormone (hGH 6--13) decreased the percentage of phosphorylase in the active form without affecting synthase activity. This action was indirect and dependent upon insulin. The peptide hGH 177--191 decreased the level of the active form of synthase without affecting phosphorylase activity. This effect was also observed with analogous peptides containing the sequence hGH 178--191 (i.e., hGH 172--191 and hGH 178--191), whereas the peptide hGH 179--191 was inert. The onset of these effects was rapid, and maximum changes in activity were produced in 5 min by both peptides. The effect for hGH 177--191 was short-lived, and synthase activity had returned to normal levels by 15 min, whereas the action of hGH 6--13 was of longer duration and was still quite marked at 60 min. Both peptides showed a linear dependence of response to the log dose of peptide injected over the range 0.1--250 microgram hGH 6--13 per kg body weight and 0.05--25 microgram hGH 177--191 per kg body weight. Hepatic 3',5'-cyclicadenylic acid levels were not affected by either peptide. Incorporation of glycerol carbon into liver glycogen was increased by hGH 6--13 and decreased by hGH carbon into liver glycogen was increased by hGH 6--13 and decreased by hGH 177--191. This is discussed in terms of a futile cycle between glycogen and hexose phosphate in the liver, as the basis for a control mechanism for hepatic glycogen metabolism. The present observations are consistent with other in vivo and in vitro actions of these and related peptides.", "contents": "Effects of part sequences of human growth hormone on in vivo hepatic glycogen metabolism in the rat. Acute effects of two part sequences of human growth hormone on the in vivo activity levels of hepatic glycogen synthase and glycogen phosphorylase were examined. The peptide corresponding to residues 6 to 13 of the hormone (hGH 6--13) decreased the percentage of phosphorylase in the active form without affecting synthase activity. This action was indirect and dependent upon insulin. The peptide hGH 177--191 decreased the level of the active form of synthase without affecting phosphorylase activity. This effect was also observed with analogous peptides containing the sequence hGH 178--191 (i.e., hGH 172--191 and hGH 178--191), whereas the peptide hGH 179--191 was inert. The onset of these effects was rapid, and maximum changes in activity were produced in 5 min by both peptides. The effect for hGH 177--191 was short-lived, and synthase activity had returned to normal levels by 15 min, whereas the action of hGH 6--13 was of longer duration and was still quite marked at 60 min. Both peptides showed a linear dependence of response to the log dose of peptide injected over the range 0.1--250 microgram hGH 6--13 per kg body weight and 0.05--25 microgram hGH 177--191 per kg body weight. Hepatic 3',5'-cyclicadenylic acid levels were not affected by either peptide. Incorporation of glycerol carbon into liver glycogen was increased by hGH 6--13 and decreased by hGH carbon into liver glycogen was increased by hGH 6--13 and decreased by hGH 177--191. This is discussed in terms of a futile cycle between glycogen and hexose phosphate in the liver, as the basis for a control mechanism for hepatic glycogen metabolism. The present observations are consistent with other in vivo and in vitro actions of these and related peptides."}
{"id": "PMID:214154", "title": "Modulation of adenylate cyclase activity by sulfated glycosaminoglycans. I. Inhibition by heparin of gonadotrophin-stimulated ovarian adenylate cyclase.", "content": "Heparin inhibits (I50 = 2 microgram/ml) the activity of luteinizing hormone and human chorionic gonadotropin-stimulated adenylate cyclase in purified rat ovarian plasma membranes. Unstimulated enzyme activity and activity stimulated by NaF, GTP or guanosine 5'-(beta,gamma-imido)triphosphate were inhibited to a lesser extent. Human chorionic gonadotropin binding to this membrane preparation was inhibited by heparin (I50 = 6 microgram/ml). The inhibition with respect to hormone concentration was of a mixed type for hormone binding and adenylate cyclase stimulation. Inhibition by heparin was not eliminated at saturating hormone concentration. The degree of inhibition was unaffected by the order in which enzyme, hormone and heparin were introduced into the assay system. Heparin (3 microgram/ml) did not affect the pH activity relationship of basal and hormone-stimulated adenylate cyclase activity and did not change the dependence of enzyme activity on magnesium ion concentration. The inhibitory action of heparin cannot be solely attributed to interference with either catalysis or hormone binding. The possibility is considered that the highly charged heparin molecule interferes with enzyme receptor coupling, by restricting the mobility of these components or by effecting their conformation.", "contents": "Modulation of adenylate cyclase activity by sulfated glycosaminoglycans. I. Inhibition by heparin of gonadotrophin-stimulated ovarian adenylate cyclase. Heparin inhibits (I50 = 2 microgram/ml) the activity of luteinizing hormone and human chorionic gonadotropin-stimulated adenylate cyclase in purified rat ovarian plasma membranes. Unstimulated enzyme activity and activity stimulated by NaF, GTP or guanosine 5'-(beta,gamma-imido)triphosphate were inhibited to a lesser extent. Human chorionic gonadotropin binding to this membrane preparation was inhibited by heparin (I50 = 6 microgram/ml). The inhibition with respect to hormone concentration was of a mixed type for hormone binding and adenylate cyclase stimulation. Inhibition by heparin was not eliminated at saturating hormone concentration. The degree of inhibition was unaffected by the order in which enzyme, hormone and heparin were introduced into the assay system. Heparin (3 microgram/ml) did not affect the pH activity relationship of basal and hormone-stimulated adenylate cyclase activity and did not change the dependence of enzyme activity on magnesium ion concentration. The inhibitory action of heparin cannot be solely attributed to interference with either catalysis or hormone binding. The possibility is considered that the highly charged heparin molecule interferes with enzyme receptor coupling, by restricting the mobility of these components or by effecting their conformation."}
{"id": "PMID:214155", "title": "A model for cyclic AMP-chemoreceptor interaction in Dictyostelium discoideum.", "content": "Based on the chemotactic activity of approximately 50 different adenosine 3',5'-cyclic-monophosphate (cyclic AMP) derivatives with substitutions at the phosphate, ribose and adenine moieties, a model for the cyclic AMP-chemoreceptor interaction in Dictyostelium discoideum is proposed. In this model the cyclic AMP molecule is bound to the receptor by three hydrogen bonds at, respectively, the 3'-oxygen of the ribose and the 6-amino and the 7-nitrogen of the base, and possibly by one ionic interaction of the negatively charged phosphate group. The conformation of the adenine moiety is in the anti range and binds additionally to the receptor by hydrophobic interactions betueen its pi-electron system and a corresponding acceptor at the active site. Although this receptor clearly differs from that involved in protein kinase activation in higher organisms, the existence of striking similarities suggests a basic mechanism for cyclic AMP interaction conserved during evolution.", "contents": "A model for cyclic AMP-chemoreceptor interaction in Dictyostelium discoideum. Based on the chemotactic activity of approximately 50 different adenosine 3',5'-cyclic-monophosphate (cyclic AMP) derivatives with substitutions at the phosphate, ribose and adenine moieties, a model for the cyclic AMP-chemoreceptor interaction in Dictyostelium discoideum is proposed. In this model the cyclic AMP molecule is bound to the receptor by three hydrogen bonds at, respectively, the 3'-oxygen of the ribose and the 6-amino and the 7-nitrogen of the base, and possibly by one ionic interaction of the negatively charged phosphate group. The conformation of the adenine moiety is in the anti range and binds additionally to the receptor by hydrophobic interactions betueen its pi-electron system and a corresponding acceptor at the active site. Although this receptor clearly differs from that involved in protein kinase activation in higher organisms, the existence of striking similarities suggests a basic mechanism for cyclic AMP interaction conserved during evolution."}
{"id": "PMID:214156", "title": "Effect of urethan on the induction of ornithine decarboxylase in regenerating rat liver.", "content": "The effect of urethan on the induction of ornithine decarboxylase in the early stage of the regeneration of rat liver was studied. The induced activity of ornithine decarboxylase was suppressed by administration of urethan immediately after partial hepatectomy. Although ornithine decarboxylase was induced biphasically by partial hepatectomy, a single intraperitoneal injection of urethan resulted in the reduction of both phases. However, the ornithine decarboxylase activity induced by glucocorticoids and growth hormone was not suppressed by urethan. The increased level of 3',5'-cyclic adenosine monophosphate induced by partial hepatectomy was also reduced by urethan and this suppression was proportional to the suppression of ornithine decarboxylase activity. Reversal of the urethan-induced suppression of ornithine decarboxylase by administration of dibutyryl 3',5'-cyclic adenosine monophosphate was also observed.", "contents": "Effect of urethan on the induction of ornithine decarboxylase in regenerating rat liver. The effect of urethan on the induction of ornithine decarboxylase in the early stage of the regeneration of rat liver was studied. The induced activity of ornithine decarboxylase was suppressed by administration of urethan immediately after partial hepatectomy. Although ornithine decarboxylase was induced biphasically by partial hepatectomy, a single intraperitoneal injection of urethan resulted in the reduction of both phases. However, the ornithine decarboxylase activity induced by glucocorticoids and growth hormone was not suppressed by urethan. The increased level of 3',5'-cyclic adenosine monophosphate induced by partial hepatectomy was also reduced by urethan and this suppression was proportional to the suppression of ornithine decarboxylase activity. Reversal of the urethan-induced suppression of ornithine decarboxylase by administration of dibutyryl 3',5'-cyclic adenosine monophosphate was also observed."}
{"id": "PMID:214157", "title": "[Assessment of the viscoelastic properties of biological membranes by measurements on bilayers].", "content": "The frequency characteristic of the complex Young modulus along the normal to surface is measured for the bilayer lipid membranes (BLM). For egg lecithin membranes the absolute value of the modulus (formula: see text) rises from 4.10(6) to 10(8) dyn/cm2 (n-decane) and from 10(8) to 10(9) dyn/cm2 (n-hexadecane) with the frequency change from 20 Hz to 15 000 Hz depending on different membrane solvents. (formula: see text) also rises several times if cholesterol is added or lipid hydrocarbon chains are longer or more saturated. If the solvent--n-hexadecane is freezed out in the region of 14 degrees C,(formula: see text) increases up to 10(10) dyn/cm2. The loss angle is measured and real and imaginary parts of (formula: see text) are determined. (formula: see text) posesses the relaxtion times spectrum in the range 10(-5)--10(-3) s. The conclusion is made that biological membranes like BLM have polymer properties, their (formula: see text) values may achieve 10(10) dyn/cm2 and the relaxation times are greater than 10(-3) s.", "contents": "[Assessment of the viscoelastic properties of biological membranes by measurements on bilayers]. The frequency characteristic of the complex Young modulus along the normal to surface is measured for the bilayer lipid membranes (BLM). For egg lecithin membranes the absolute value of the modulus (formula: see text) rises from 4.10(6) to 10(8) dyn/cm2 (n-decane) and from 10(8) to 10(9) dyn/cm2 (n-hexadecane) with the frequency change from 20 Hz to 15 000 Hz depending on different membrane solvents. (formula: see text) also rises several times if cholesterol is added or lipid hydrocarbon chains are longer or more saturated. If the solvent--n-hexadecane is freezed out in the region of 14 degrees C,(formula: see text) increases up to 10(10) dyn/cm2. The loss angle is measured and real and imaginary parts of (formula: see text) are determined. (formula: see text) posesses the relaxtion times spectrum in the range 10(-5)--10(-3) s. The conclusion is made that biological membranes like BLM have polymer properties, their (formula: see text) values may achieve 10(10) dyn/cm2 and the relaxation times are greater than 10(-3) s."}
{"id": "PMID:214158", "title": "[EPR study of oxidative phosphorylation in surviving mitochondria].", "content": "Rat liver mitochondria were studied by ESR method in an original flow-type system, which allowed to maintain adequate conditions for survival. Low sensitivity of modern ESR-spectrometers for humid samples requires high concentrations of mitochondrial protein, which puts additional requirements for the survival of the sample. It is most important to create the level of oxidation substrates, phosphate acceptors and oxygen content sufficient for the normal course of oxidation and phosphorylation. The flow-type system applied makes it possible to overcome the above difficulties and permits biochemical control over the object state to be realized throughout the ESR spectrum recordings. Estimation of oxidative and phosphorylating activity of mitochondria has shown that the system makes it possible to realize all the metabolic transitions up to their maximal stimulation when passing to an active state.", "contents": "[EPR study of oxidative phosphorylation in surviving mitochondria]. Rat liver mitochondria were studied by ESR method in an original flow-type system, which allowed to maintain adequate conditions for survival. Low sensitivity of modern ESR-spectrometers for humid samples requires high concentrations of mitochondrial protein, which puts additional requirements for the survival of the sample. It is most important to create the level of oxidation substrates, phosphate acceptors and oxygen content sufficient for the normal course of oxidation and phosphorylation. The flow-type system applied makes it possible to overcome the above difficulties and permits biochemical control over the object state to be realized throughout the ESR spectrum recordings. Estimation of oxidative and phosphorylating activity of mitochondria has shown that the system makes it possible to realize all the metabolic transitions up to their maximal stimulation when passing to an active state."}
{"id": "PMID:214163", "title": "Regulation of purine biosynthesis in cultured Drosophila melanogaster cells: I.--Conditional activity of hypoxanthine-guanine-phosphoribosyltransferase and 5-nucleotidase.", "content": "In cultured cells established from Drosophila melanogaster embryos, and grown in usual medium, no hypoxanthine-guanine-phosphoribosyl transferase (HG-PRT) could be measured, and only traces of 5'-nucleotidase activity were detectable. On the contrary, it was observed that if the same medium is supplemented with purine bases, nucleosides, orotate, glutamine, azaserine or antifolates, de novo purine biosynthesis is inhibited, and HGPRT is detectable, along with an important 5'-nucleotidase activity. Moreover, dialysis or treatment of extracts from cells untreated by purines, with activated charcoal restored HGPRT and 5'-nucleotidase activities. These activities were abolished completely by inosinic acid (IMP) and guanosine 5'-monophosphoric acid (GMP). Similar results were obtained with fly extracts. These results suggest that de novo purine biosynthesis masks HGPRT activity, the endogenous synthesis leading to the accumulation of purine nucleotides which are inhibitors of the HGPRT activity.", "contents": "Regulation of purine biosynthesis in cultured Drosophila melanogaster cells: I.--Conditional activity of hypoxanthine-guanine-phosphoribosyltransferase and 5-nucleotidase. In cultured cells established from Drosophila melanogaster embryos, and grown in usual medium, no hypoxanthine-guanine-phosphoribosyl transferase (HG-PRT) could be measured, and only traces of 5'-nucleotidase activity were detectable. On the contrary, it was observed that if the same medium is supplemented with purine bases, nucleosides, orotate, glutamine, azaserine or antifolates, de novo purine biosynthesis is inhibited, and HGPRT is detectable, along with an important 5'-nucleotidase activity. Moreover, dialysis or treatment of extracts from cells untreated by purines, with activated charcoal restored HGPRT and 5'-nucleotidase activities. These activities were abolished completely by inosinic acid (IMP) and guanosine 5'-monophosphoric acid (GMP). Similar results were obtained with fly extracts. These results suggest that de novo purine biosynthesis masks HGPRT activity, the endogenous synthesis leading to the accumulation of purine nucleotides which are inhibitors of the HGPRT activity."}
{"id": "PMID:214164", "title": "Phosphatidic and lysophosphatidic acid production in phospholipase C-and thrombin-treated platelets. Possible involvement of a platelet lipase.", "content": "Incubation of 32P-labelled platelets with Clostridium welchii phospholipase C greatly stimulates 32P-incorporation into phosphatidic and lysophosphatidic acids. A net synthesis is demonstrated for both phospholipids, which exhibit identical specific radioactivities. Phosphatidic acid production roughly parallels the phospholipase C-induced aggregation, whereas lysophosphatidic acid appears secondarily during cell lysis. The same qualitative variations are observed during thrombin-induced aggregation. At the physiological pH used throughout the incubations, platelets display no phospholipase A activity towards phosphatidic acid, whereas diglycerides are deacylated by platelet lysates. On the basis of these findings, a mechanism for phosphatidic and lysophosphatidic acid production is proposed, involving a phosphorylation of the di- and monoglycerides formed upon phospholipase C and lipase action. The possible role of such a pathway in regulating arachidonic acid release from phospholipids during platelet activation is discussed.", "contents": "Phosphatidic and lysophosphatidic acid production in phospholipase C-and thrombin-treated platelets. Possible involvement of a platelet lipase. Incubation of 32P-labelled platelets with Clostridium welchii phospholipase C greatly stimulates 32P-incorporation into phosphatidic and lysophosphatidic acids. A net synthesis is demonstrated for both phospholipids, which exhibit identical specific radioactivities. Phosphatidic acid production roughly parallels the phospholipase C-induced aggregation, whereas lysophosphatidic acid appears secondarily during cell lysis. The same qualitative variations are observed during thrombin-induced aggregation. At the physiological pH used throughout the incubations, platelets display no phospholipase A activity towards phosphatidic acid, whereas diglycerides are deacylated by platelet lysates. On the basis of these findings, a mechanism for phosphatidic and lysophosphatidic acid production is proposed, involving a phosphorylation of the di- and monoglycerides formed upon phospholipase C and lipase action. The possible role of such a pathway in regulating arachidonic acid release from phospholipids during platelet activation is discussed."}
{"id": "PMID:214165", "title": "[Several properties of 3':5'-AMP-dependent skeletal muscle protein kinases in normal rats and following physical exertion to fatigue].", "content": "Three fractions of rat adenosine-3',5'-monophosphate-dependent protein kinase were isolated, partially purified in buffer concentration gradient at normal state and after long-term physical loading and studied. It is found that first two fractions of protein kinases at normal state and after intensive muscular work have similar activities with and without cAMP, apparent Km values for ATP and total histone and half-maximal stimulation by cyclic AMP, but they differed from the third fraction. There are differences in some kinetic parameters and in the cyclic AMP stimulated activities between protein kinases after physical loading. The data obtained suggest the existence of at least two kinases in rat skeletal muscle. The isoenzymes differ in their activities during fatigue.", "contents": "[Several properties of 3':5'-AMP-dependent skeletal muscle protein kinases in normal rats and following physical exertion to fatigue]. Three fractions of rat adenosine-3',5'-monophosphate-dependent protein kinase were isolated, partially purified in buffer concentration gradient at normal state and after long-term physical loading and studied. It is found that first two fractions of protein kinases at normal state and after intensive muscular work have similar activities with and without cAMP, apparent Km values for ATP and total histone and half-maximal stimulation by cyclic AMP, but they differed from the third fraction. There are differences in some kinetic parameters and in the cyclic AMP stimulated activities between protein kinases after physical loading. The data obtained suggest the existence of at least two kinases in rat skeletal muscle. The isoenzymes differ in their activities during fatigue."}
{"id": "PMID:214166", "title": "[Phosphohydrolases of the phytopathogenic fungus Phytophthora infestans (Mont) de Bary].", "content": "ATPase, pyrophosphatase and tripolyhosphatase activities were found in a cell-free Phytophtora infestans micelium extract. No polyphosphatase activity, hydrolyzing high molecular weigh polyphosphates to orthophosphate, was observed in the fungi. It was demonstrated that, unlike ATPase, the activity of pyrophosphatase was inhibited by Ca2+ at concentrations from 0.1 to 20 mM, and it was considerably decreased in the presence of a Ca2+ transport inhibitor, ruthenium red (0.01--0.1 mM). Possible relation of Ph. infestans pyrophosphatase activity with the process of active calcium transport is suggested.", "contents": "[Phosphohydrolases of the phytopathogenic fungus Phytophthora infestans (Mont) de Bary]. ATPase, pyrophosphatase and tripolyhosphatase activities were found in a cell-free Phytophtora infestans micelium extract. No polyphosphatase activity, hydrolyzing high molecular weigh polyphosphates to orthophosphate, was observed in the fungi. It was demonstrated that, unlike ATPase, the activity of pyrophosphatase was inhibited by Ca2+ at concentrations from 0.1 to 20 mM, and it was considerably decreased in the presence of a Ca2+ transport inhibitor, ruthenium red (0.01--0.1 mM). Possible relation of Ph. infestans pyrophosphatase activity with the process of active calcium transport is suggested."}
{"id": "PMID:214167", "title": "[Regulatory interaction between the respiratory chain of mitochondria and the oxidative system of the endoplasmic reticulum].", "content": "A regulation mechanism of the interaction of microsomal oxidases and mitochondrial respiratory chain with oxidase substrates is suggested. Quantitative comparison of their affinity to microsomal oxidases and mitochondrial NADH-dehydrogenase is carried out. The interaction with both systems is found to be hydrophobic. It is found that microsomal oxidase substrates inhibit mitochondrial NADH-dehydrogenase at concentrations, which should completely fill the active site of cytochrome P-450. It is suggested that redistribution of reduced equivalents from mitochondria to microsomes and the acceleration of xenobiotic detoxication take place.", "contents": "[Regulatory interaction between the respiratory chain of mitochondria and the oxidative system of the endoplasmic reticulum]. A regulation mechanism of the interaction of microsomal oxidases and mitochondrial respiratory chain with oxidase substrates is suggested. Quantitative comparison of their affinity to microsomal oxidases and mitochondrial NADH-dehydrogenase is carried out. The interaction with both systems is found to be hydrophobic. It is found that microsomal oxidase substrates inhibit mitochondrial NADH-dehydrogenase at concentrations, which should completely fill the active site of cytochrome P-450. It is suggested that redistribution of reduced equivalents from mitochondria to microsomes and the acceleration of xenobiotic detoxication take place."}
{"id": "PMID:214168", "title": "[Mechanism of brain Na,K-ATPase activation by adrenaline].", "content": "Norepinephrine stimulates Na, K-ATPase from rat brain homogenates at concentrations of 10(-4)--10(-5) and 10(-7)--10(-8) M. A low concentration maximum is observed after 48 hrs of incubation at -20 degrees C and is not changed by the addition of alpha-tocopherol, glycerol and MAO inhibitor ipraside. The maximum observed at the mediator concentration equal to 10(-4)--10(-5) M is eliminated after treatment with EGTA. At all concentrations of norepinephrine the enzyme stimulation is removed by the alpha-adrenoblocker phentolamine. The activated enzyme reveals lower sensitivity to Ca2+ induced inhibition. The role of Ca2+ and conformational state of the membranes in the realization of the remote effect on the adrenoreceptor-Na, K-ATPase system is discussed.", "contents": "[Mechanism of brain Na,K-ATPase activation by adrenaline]. Norepinephrine stimulates Na, K-ATPase from rat brain homogenates at concentrations of 10(-4)--10(-5) and 10(-7)--10(-8) M. A low concentration maximum is observed after 48 hrs of incubation at -20 degrees C and is not changed by the addition of alpha-tocopherol, glycerol and MAO inhibitor ipraside. The maximum observed at the mediator concentration equal to 10(-4)--10(-5) M is eliminated after treatment with EGTA. At all concentrations of norepinephrine the enzyme stimulation is removed by the alpha-adrenoblocker phentolamine. The activated enzyme reveals lower sensitivity to Ca2+ induced inhibition. The role of Ca2+ and conformational state of the membranes in the realization of the remote effect on the adrenoreceptor-Na, K-ATPase system is discussed."}
{"id": "PMID:214169", "title": "[Chemiluminescence during oxidation of gossipol by peroxidase].", "content": "Gossipol oxidation with peroxidase accompanied by chemiluminescence is revealed. Effect of some factors on chemiluminescence is investigated. Peroxidase gossipol oxidation is suggested to be one of the causes of spontaneous cotton root luminescence. Chemiluminescence in the system studied is inhibited by superoxide dismutase, which indicates the generation of superoxide anion radical. It is suggested that these radicals and other activated oxygen species are involved in the gossipol toxicity for parasitic microorganisms.", "contents": "[Chemiluminescence during oxidation of gossipol by peroxidase]. Gossipol oxidation with peroxidase accompanied by chemiluminescence is revealed. Effect of some factors on chemiluminescence is investigated. Peroxidase gossipol oxidation is suggested to be one of the causes of spontaneous cotton root luminescence. Chemiluminescence in the system studied is inhibited by superoxide dismutase, which indicates the generation of superoxide anion radical. It is suggested that these radicals and other activated oxygen species are involved in the gossipol toxicity for parasitic microorganisms."}
{"id": "PMID:214171", "title": "[Effect of mutations in regulatory genes for alkaline phosphatase on the phosphohydrolase spectrum of E. coli periplasm].", "content": "The isoform spectra of alkaline and acid phosphatase, pyrophosphataes, and ATPase in periplasm of E. coli were studied using electrophoresis in polyacrylamide gel with subsequent development of zimograms directly in the gel. Wild strains and mutants on 4 regulatory genes of alkaline phosphatase were analyzed. Mutations in regulatory genes were shown to influence the amount of each of the 3 isoforms of alkaline phosphatase and also the spectra of other phosphohydrolases.", "contents": "[Effect of mutations in regulatory genes for alkaline phosphatase on the phosphohydrolase spectrum of E. coli periplasm]. The isoform spectra of alkaline and acid phosphatase, pyrophosphataes, and ATPase in periplasm of E. coli were studied using electrophoresis in polyacrylamide gel with subsequent development of zimograms directly in the gel. Wild strains and mutants on 4 regulatory genes of alkaline phosphatase were analyzed. Mutations in regulatory genes were shown to influence the amount of each of the 3 isoforms of alkaline phosphatase and also the spectra of other phosphohydrolases."}
{"id": "PMID:214170", "title": "[Separation and investigation of the regulatory properties of two forms of cyclic nucleotide phosphodiesterase from rabbit heart--sensitive and insensitive to Ca-dependent regulator protein].", "content": "Two forms of cyclic nucleotide phosphodiesterase (ES 3.1.4.17)--PDE-I and PDE-II--sensitive and resistant to Ca-dependent protein regulator, were isolated from the soluble fraction of rabbit heart by chromatography on DEAE-cellulose. Both forms of enzyme are inhibited by 30--50% by Ca2+ (10(-4) M). Addition of Ca-dependent protein regulator activates PDE-I and eliminates Ca2+-induced inhibition of PDE-II. In heart extract Ca2+ increases the phosphodiesterase activity 1.5-fold. The amount of PDE-I makes up to about 10% of total phosphodiesterase activity of the heart; that of PDE-II is about 90%. In the presence of Ca-dependent protein regulator the rate of 3', 5'-AMP hydrolysis by PDE-I is increased 5--15-fold, while that of 3', 5'-GMP hydrolysis only 2.5-fold. Both PDE-I and PDE-II have close Km values for substrates--(3.5--4.0).10(-6) M for 3', 5'-AMP and 14.10(-6) M for 3', 5'-GMP. Inhibition by Ca2+ and effect of Ca-dependent protein regulator manifest themselves in changes in V for cyclic nucleotide hydrolysis and do not alter the Km value for the enzyme.", "contents": "[Separation and investigation of the regulatory properties of two forms of cyclic nucleotide phosphodiesterase from rabbit heart--sensitive and insensitive to Ca-dependent regulator protein]. Two forms of cyclic nucleotide phosphodiesterase (ES 3.1.4.17)--PDE-I and PDE-II--sensitive and resistant to Ca-dependent protein regulator, were isolated from the soluble fraction of rabbit heart by chromatography on DEAE-cellulose. Both forms of enzyme are inhibited by 30--50% by Ca2+ (10(-4) M). Addition of Ca-dependent protein regulator activates PDE-I and eliminates Ca2+-induced inhibition of PDE-II. In heart extract Ca2+ increases the phosphodiesterase activity 1.5-fold. The amount of PDE-I makes up to about 10% of total phosphodiesterase activity of the heart; that of PDE-II is about 90%. In the presence of Ca-dependent protein regulator the rate of 3', 5'-AMP hydrolysis by PDE-I is increased 5--15-fold, while that of 3', 5'-GMP hydrolysis only 2.5-fold. Both PDE-I and PDE-II have close Km values for substrates--(3.5--4.0).10(-6) M for 3', 5'-AMP and 14.10(-6) M for 3', 5'-GMP. Inhibition by Ca2+ and effect of Ca-dependent protein regulator manifest themselves in changes in V for cyclic nucleotide hydrolysis and do not alter the Km value for the enzyme."}
{"id": "PMID:214172", "title": "[Reverse electron transfer from the cytochrome c level in cyanide-resistant mitochondria of the yeast, Candida lipolytica].", "content": "The ability of cyanide-resistant mitochondria of yeast Candida lipolytica to perform reverse electron transfer from cytochrome c to alternative oxidase was studied. It was shown that the energy for such a transfer can be provided by high energy intermediates or membrane potential but not by ATP. Reverse electron transfer from cytochrome c is impossible due to energy of NADH and alpha-glycerophosphate oxidation via alternative pathway in the presence of cyanide. These results prove once again that electron transfer via alternative pathway is not connected with the energy accumulation.", "contents": "[Reverse electron transfer from the cytochrome c level in cyanide-resistant mitochondria of the yeast, Candida lipolytica]. The ability of cyanide-resistant mitochondria of yeast Candida lipolytica to perform reverse electron transfer from cytochrome c to alternative oxidase was studied. It was shown that the energy for such a transfer can be provided by high energy intermediates or membrane potential but not by ATP. Reverse electron transfer from cytochrome c is impossible due to energy of NADH and alpha-glycerophosphate oxidation via alternative pathway in the presence of cyanide. These results prove once again that electron transfer via alternative pathway is not connected with the energy accumulation."}
{"id": "PMID:214173", "title": "[HDL2c--a new subclass of high density lipoproteins in the plasma of newborns].", "content": "A new subclass of high density lipoproteins designated as HLD2c was found in the human blood plasma of newborn by analytic ultracentrifugation in the flotation rate interval Fo1,20 8.0--12.0. HDL2c was isolated from the total HDL fraction of newborn by preparative ultracentrifugation at the density 1.071.", "contents": "[HDL2c--a new subclass of high density lipoproteins in the plasma of newborns]. A new subclass of high density lipoproteins designated as HLD2c was found in the human blood plasma of newborn by analytic ultracentrifugation in the flotation rate interval Fo1,20 8.0--12.0. HDL2c was isolated from the total HDL fraction of newborn by preparative ultracentrifugation at the density 1.071."}
{"id": "PMID:214180", "title": "EBNA antibodies are more useful than complement fixing antibodies in monitoring infectious mononucleosis patients.", "content": "Thirty-six patients with infectious mononucleosis (IM) were followed prospectively for both anti-Epstein-Barr virus nuclear antigen (EBNA) and complement-fixing antibodies using the soluble EBV antigen (CF/S). Discrepancies in time between the two reactivities were found, due to the differences in sensitivity of the tests. It is suggested that, in clinical virology laboratories, EBNA and not CF/S tests be used.", "contents": "EBNA antibodies are more useful than complement fixing antibodies in monitoring infectious mononucleosis patients. Thirty-six patients with infectious mononucleosis (IM) were followed prospectively for both anti-Epstein-Barr virus nuclear antigen (EBNA) and complement-fixing antibodies using the soluble EBV antigen (CF/S). Discrepancies in time between the two reactivities were found, due to the differences in sensitivity of the tests. It is suggested that, in clinical virology laboratories, EBNA and not CF/S tests be used."}
{"id": "PMID:214181", "title": "Distribution of adenosine 5'-triphosphate (ATP)-dependent hexose kinases in microorganisms.", "content": "A systematic study of adenosine triphosphate (ATP)-dependent hexose kinases among microorganisms has been undertaken. Sixteen hexose kinases of five major types were partially purified from 12 microorganisms and characterized with respect to specificity for sugar and nucleotide substrates and Michaelis constants for the sugar substrates. Glucokinase activities that phosphorylate glucose and glucosamine are inhibited by N-acetyl-glucosamine and xylose, were found to be present in the non-sulphur photosynthetic bacteria Rhodospirillum rubrum, the blue-green algae Anacystis montana, and the protists Chlorella pyrenoidosa and Chlamydomonas reinhardtii (green algae), Hypochytrium catenoides (Hypochytridiomycete) and Saprolegnia Iitoralis (Oomycete). The myxobacteria Stigmatella aurantiaca contains a glucokinase activity with a different specificity pattern. Anacystis and Chlorella, besides their glucokinase activities, contain highly specific fructokinases, although that from Anacystis can also phosphorylate fructosamine; fructokinase from Anacystis has a molecular weight of 20 000, and exhibits a sigmoidal saturation curve for ATP when the Mg2+/ATP ratio is 2; this curve is transformed to a Michaelian one when under the same conditions an excess of Mg2+ (5 mM) is added. Saprolegnia however, besides the glucokinase, contains a mannofructokinase activity that phosphorylates mannose (Km 0.06 mM) and fructose (1 mM). On the other hand, hexokinase, a low specificity enzyme, was detected in the protist Allomyces arbuscula (Chytridiomycete) and in fungi Mucor hiemalis and Phycomyces blakesleeanus (Zygomycetes), and Schizophyllum commune (Basidiomycete). Schizophyllum contains a glucomannokinase activity together with hexokinase activity. The pattern of distribution of ATP-dependent hexose kinases among microorganisms seems to parallel that reported for biosynthetic pathways for lysine. The correlation with other biochemical parameters is also considered.", "contents": "Distribution of adenosine 5'-triphosphate (ATP)-dependent hexose kinases in microorganisms. A systematic study of adenosine triphosphate (ATP)-dependent hexose kinases among microorganisms has been undertaken. Sixteen hexose kinases of five major types were partially purified from 12 microorganisms and characterized with respect to specificity for sugar and nucleotide substrates and Michaelis constants for the sugar substrates. Glucokinase activities that phosphorylate glucose and glucosamine are inhibited by N-acetyl-glucosamine and xylose, were found to be present in the non-sulphur photosynthetic bacteria Rhodospirillum rubrum, the blue-green algae Anacystis montana, and the protists Chlorella pyrenoidosa and Chlamydomonas reinhardtii (green algae), Hypochytrium catenoides (Hypochytridiomycete) and Saprolegnia Iitoralis (Oomycete). The myxobacteria Stigmatella aurantiaca contains a glucokinase activity with a different specificity pattern. Anacystis and Chlorella, besides their glucokinase activities, contain highly specific fructokinases, although that from Anacystis can also phosphorylate fructosamine; fructokinase from Anacystis has a molecular weight of 20 000, and exhibits a sigmoidal saturation curve for ATP when the Mg2+/ATP ratio is 2; this curve is transformed to a Michaelian one when under the same conditions an excess of Mg2+ (5 mM) is added. Saprolegnia however, besides the glucokinase, contains a mannofructokinase activity that phosphorylates mannose (Km 0.06 mM) and fructose (1 mM). On the other hand, hexokinase, a low specificity enzyme, was detected in the protist Allomyces arbuscula (Chytridiomycete) and in fungi Mucor hiemalis and Phycomyces blakesleeanus (Zygomycetes), and Schizophyllum commune (Basidiomycete). Schizophyllum contains a glucomannokinase activity together with hexokinase activity. The pattern of distribution of ATP-dependent hexose kinases among microorganisms seems to parallel that reported for biosynthetic pathways for lysine. The correlation with other biochemical parameters is also considered."}
{"id": "PMID:214182", "title": "[Cortisol, adrenocorticotropic hormone and apolipoprotein synthesis in rat hepatocytes].", "content": "The influence of cortisol (5 mg/kg body wt administered daily for 5 and 10 days) on biosynthesis of apoproteins of lipoproteins of very low density in the liver and on the synthesis of apolipoproteins of very low, low, and high density (VLDL, LDL, and HDL apoproteins, respectively) in the blood serum of adrenalectomized animals, and after replacement cortisol therapy was studied. Cortisol treatment during these periods resulted in the VLDL apoproteins biosynthesis inhibition in the rat liver. The synthesis of apolipoproteins was increased by adrenalectomy; this effect was eliminated after replacement cortisol treatment. The apoprotein synthesis was stimulated within 5 hours by single injection of cortisol or ACTH. Study of the blood serum apolipoproteins specific radioactivity indicated metabolic change of lipoproteins, such as disturbed conversion from VLDL to LDL. Single and prolonged cortisol administration led to the opposite results. The authors believe that the metabolic disturbances of lipoproteins in the blood play a more important role in the pathogenesis of cortisol-induced hyperlipidemia than lipoprotein syntesis stimulation in the liver.", "contents": "[Cortisol, adrenocorticotropic hormone and apolipoprotein synthesis in rat hepatocytes]. The influence of cortisol (5 mg/kg body wt administered daily for 5 and 10 days) on biosynthesis of apoproteins of lipoproteins of very low density in the liver and on the synthesis of apolipoproteins of very low, low, and high density (VLDL, LDL, and HDL apoproteins, respectively) in the blood serum of adrenalectomized animals, and after replacement cortisol therapy was studied. Cortisol treatment during these periods resulted in the VLDL apoproteins biosynthesis inhibition in the rat liver. The synthesis of apolipoproteins was increased by adrenalectomy; this effect was eliminated after replacement cortisol treatment. The apoprotein synthesis was stimulated within 5 hours by single injection of cortisol or ACTH. Study of the blood serum apolipoproteins specific radioactivity indicated metabolic change of lipoproteins, such as disturbed conversion from VLDL to LDL. Single and prolonged cortisol administration led to the opposite results. The authors believe that the metabolic disturbances of lipoproteins in the blood play a more important role in the pathogenesis of cortisol-induced hyperlipidemia than lipoprotein syntesis stimulation in the liver."}
{"id": "PMID:214183", "title": "[Effect of adrenaline, hydrocortisone, insulin and dibutyryl-cAMP on glycolysis and glycogenolysis in white rat liver slices].", "content": "Epinephrine, hydrocortisone, and dibutyril cAMP inhibited glycolysis and glucogenolysis. The inhibitory effect was also found when glucose-6-phosphate (G-6-P) was used as a glycolysis substrate, but not for fructose-1,6-diphosphate. This is the evidence of hexokinase activity inhibition by hormones and dibutyril cAMP, and presumably of phospholylase and phosphofructokinase as well. In the simulated cell-free system the hormones produced no effect, dibutyril cAMP inhibiting hexokinase alone. For the realization of hormones effect their interaction with the cell membrane is required. Inhibition of glycogen and G-6-P decomposition to lactic acid in the rat liver slices was not associated with the hormone action on phosphorylase and phosphofructokinase through cAMP and proteinkinase directly. The results obtained indicated the existence of a supplementary mechanism that modified cAMP effect on the activity of the said enzymes. Insulin was effective in any of the cases.", "contents": "[Effect of adrenaline, hydrocortisone, insulin and dibutyryl-cAMP on glycolysis and glycogenolysis in white rat liver slices]. Epinephrine, hydrocortisone, and dibutyril cAMP inhibited glycolysis and glucogenolysis. The inhibitory effect was also found when glucose-6-phosphate (G-6-P) was used as a glycolysis substrate, but not for fructose-1,6-diphosphate. This is the evidence of hexokinase activity inhibition by hormones and dibutyril cAMP, and presumably of phospholylase and phosphofructokinase as well. In the simulated cell-free system the hormones produced no effect, dibutyril cAMP inhibiting hexokinase alone. For the realization of hormones effect their interaction with the cell membrane is required. Inhibition of glycogen and G-6-P decomposition to lactic acid in the rat liver slices was not associated with the hormone action on phosphorylase and phosphofructokinase through cAMP and proteinkinase directly. The results obtained indicated the existence of a supplementary mechanism that modified cAMP effect on the activity of the said enzymes. Insulin was effective in any of the cases."}
{"id": "PMID:214184", "title": "[Effect of preservation with metaperiodate and glutaraldehyde on the immunogenic properties of vessels].", "content": "Experiments were conducted on guinea pigs and rabbits. It was shown that treatment of human femoral vessels with metaperiodate and glutaraldehyde solutions led to a sharp (10-fold) reduction of the amount of water-soluble proteins in the tissue homogenates, to a decrease of the sensitising and anaphylactic activity of the extracts, to inertia in the precipitation test with homologous antiserum to crude tissue.", "contents": "[Effect of preservation with metaperiodate and glutaraldehyde on the immunogenic properties of vessels]. Experiments were conducted on guinea pigs and rabbits. It was shown that treatment of human femoral vessels with metaperiodate and glutaraldehyde solutions led to a sharp (10-fold) reduction of the amount of water-soluble proteins in the tissue homogenates, to a decrease of the sensitising and anaphylactic activity of the extracts, to inertia in the precipitation test with homologous antiserum to crude tissue."}
{"id": "PMID:214185", "title": "[Localization of specific antigen in the organs of newborn animals vaccinated with liver smallpox vaccine].", "content": "Of 20 suckling rabbits, 4-5-days old, inoculated with live smallpox vaccine intradermally 6 displayed symptoms of generalized pox virus and neuroparalysis complications. Intensive accumulation of specific antigen in the brain, lungs, spleen, and the lymph glands was revealed by immunofluorescent method. The smallpox vaccine virus was isolated from these organs. Prolonged persistance of the attenuated smallpox virus was observed in the brain, spinal cord, lungs, spleen, and the lymph glands of 14 suckling rabbits showing no signs of any disease; specific antigen was revealed by immunofluorescent test. Vascular disturbances and slight cell changes were observed in the brain tissue of the inoculated animals. These changes were more severe in the sick animals.", "contents": "[Localization of specific antigen in the organs of newborn animals vaccinated with liver smallpox vaccine]. Of 20 suckling rabbits, 4-5-days old, inoculated with live smallpox vaccine intradermally 6 displayed symptoms of generalized pox virus and neuroparalysis complications. Intensive accumulation of specific antigen in the brain, lungs, spleen, and the lymph glands was revealed by immunofluorescent method. The smallpox vaccine virus was isolated from these organs. Prolonged persistance of the attenuated smallpox virus was observed in the brain, spinal cord, lungs, spleen, and the lymph glands of 14 suckling rabbits showing no signs of any disease; specific antigen was revealed by immunofluorescent test. Vascular disturbances and slight cell changes were observed in the brain tissue of the inoculated animals. These changes were more severe in the sick animals."}
{"id": "PMID:214186", "title": "[Relationship between group G chromosomes, especially chromosome 21, and the sensitivity of human cells to Coxsackie B viruses].", "content": "The R-method of differential chromosome staining by length was applied to comparative karyological studies on the culture of J 96 human cells susceptible to enteroviruses, and on the J 41 cell line derived from this culture and possessing high specific resistance to Coxsackie B viruses. Karyotype of the J 41 cell line was shown to be deprived of chromosome G21 (P less than 0.0001). The number of other chromosomes varied from cell to cell, but they are constantly present in the majority of cells of both the J 96 and J 41 cell lines. A conclusion is drawn that chromosome G21 incorporates gene(s) which controls the human cells susceptibility to Coxsackie B viruses.", "contents": "[Relationship between group G chromosomes, especially chromosome 21, and the sensitivity of human cells to Coxsackie B viruses]. The R-method of differential chromosome staining by length was applied to comparative karyological studies on the culture of J 96 human cells susceptible to enteroviruses, and on the J 41 cell line derived from this culture and possessing high specific resistance to Coxsackie B viruses. Karyotype of the J 41 cell line was shown to be deprived of chromosome G21 (P less than 0.0001). The number of other chromosomes varied from cell to cell, but they are constantly present in the majority of cells of both the J 96 and J 41 cell lines. A conclusion is drawn that chromosome G21 incorporates gene(s) which controls the human cells susceptibility to Coxsackie B viruses."}
{"id": "PMID:214188", "title": "Inflammatory reactions induced by ultraviolet irradiation.", "content": "Exposure of human skin to short wavelength ultraviolet (U.V.) leads to increased concentrations of arachidonic acid and prostaglandins E2 and F2, but their role is uncertain. Although the levels of prostaglandins rise as erythema develops the correlation between intensity of erythema and prostaglandin activity is incomplete. There is mounting evidence that prostaglandins may regulate epidermal cell growth and differentiation through a cyclic-AMP dependent mechanism. The possibility therefore arises that prostaglandins, released in response to U. V. exposure, reduce proliferative activity in the exposed epidermis. This can be expected, in turn, to result in protection of skin from the mutagenic action of U. V. irradiation.", "contents": "Inflammatory reactions induced by ultraviolet irradiation. Exposure of human skin to short wavelength ultraviolet (U.V.) leads to increased concentrations of arachidonic acid and prostaglandins E2 and F2, but their role is uncertain. Although the levels of prostaglandins rise as erythema develops the correlation between intensity of erythema and prostaglandin activity is incomplete. There is mounting evidence that prostaglandins may regulate epidermal cell growth and differentiation through a cyclic-AMP dependent mechanism. The possibility therefore arises that prostaglandins, released in response to U. V. exposure, reduce proliferative activity in the exposed epidermis. This can be expected, in turn, to result in protection of skin from the mutagenic action of U. V. irradiation."}
{"id": "PMID:214189", "title": "Ultraviolet light induction of skin carcinoma in the mouse; influence of cAMP modifying agents.", "content": "A short review of pathogenic factors in U.V. light skin carcinogenesis in the mouse is presented. Caffeine and theophylline applied locally during U.V. irradiation caused a 50 percent reduction of skin tumour induction in Swiss mice. These two chemicals are inhibitors of DNA postreplication repair, but they also raise the intracellular level of cyclic AMP by inhibiting cAMP phosphodiesterase with, as a consequence, a possible slowing down of cellular growth. Control experiments using three different chemicals capable of raising the cAMP level in epidermal cells gave negative results. These experimental data are compatible with our original hypothesis according to which production of skin cancers by U.V. radiation is in same way related to DNA repair which helps the cell to survive but allows or favours the occurrence of errors in cellular DNA.", "contents": "Ultraviolet light induction of skin carcinoma in the mouse; influence of cAMP modifying agents. A short review of pathogenic factors in U.V. light skin carcinogenesis in the mouse is presented. Caffeine and theophylline applied locally during U.V. irradiation caused a 50 percent reduction of skin tumour induction in Swiss mice. These two chemicals are inhibitors of DNA postreplication repair, but they also raise the intracellular level of cyclic AMP by inhibiting cAMP phosphodiesterase with, as a consequence, a possible slowing down of cellular growth. Control experiments using three different chemicals capable of raising the cAMP level in epidermal cells gave negative results. These experimental data are compatible with our original hypothesis according to which production of skin cancers by U.V. radiation is in same way related to DNA repair which helps the cell to survive but allows or favours the occurrence of errors in cellular DNA."}
{"id": "PMID:214190", "title": "Herpes virus production as a marker of repair in ultraviolet irradiated human skin cells of different origin.", "content": "When confluent human skin cultures are ultraviolet (UV)-irradiated before infection with Herpes Simplex type 1 virus (HSV), their capacity to support virus growth is impaired. When the time interval between UV-exposure and infection is increased up to 36 hours, different recoveries of HSV production capacity are observed according to the origin of the host cells. 1) Two normal donors: the cells present a dose dependent recovery which is maximal for a dose ( : formula: (see text) at which a plateau level of unscheduled DNA synthesis (UDS) is reached. 2) A mother of two Xeroderma Pigmentosum (XP) children: in this line which exhibits a normal level of UDS, the extent of recovery is significantly decreased after exposures : formula: (see text) 3) An XP child: these cells have a normal level of UDS (XP variant) whereas they present a low extent of recovery as compared with that of the normal subjects. 4) Five XP children: in these excision deficient lines (UDS less than 15%), HSV production capacity decreases with increasing time intervals after UV exposure for doses greater than or equal to 3 : formula: (see text). For doses less than 3 : formula: (see text), a small recovery with an overshoot of viral production is observed 24 h after UV exposure in the lines (three) which present the highest UDS (10--15%) and not in the two lines which present a very low UDS (1--2%).", "contents": "Herpes virus production as a marker of repair in ultraviolet irradiated human skin cells of different origin. When confluent human skin cultures are ultraviolet (UV)-irradiated before infection with Herpes Simplex type 1 virus (HSV), their capacity to support virus growth is impaired. When the time interval between UV-exposure and infection is increased up to 36 hours, different recoveries of HSV production capacity are observed according to the origin of the host cells. 1) Two normal donors: the cells present a dose dependent recovery which is maximal for a dose ( : formula: (see text) at which a plateau level of unscheduled DNA synthesis (UDS) is reached. 2) A mother of two Xeroderma Pigmentosum (XP) children: in this line which exhibits a normal level of UDS, the extent of recovery is significantly decreased after exposures : formula: (see text) 3) An XP child: these cells have a normal level of UDS (XP variant) whereas they present a low extent of recovery as compared with that of the normal subjects. 4) Five XP children: in these excision deficient lines (UDS less than 15%), HSV production capacity decreases with increasing time intervals after UV exposure for doses greater than or equal to 3 : formula: (see text). For doses less than 3 : formula: (see text), a small recovery with an overshoot of viral production is observed 24 h after UV exposure in the lines (three) which present the highest UDS (10--15%) and not in the two lines which present a very low UDS (1--2%)."}
{"id": "PMID:214192", "title": "The effect of in vivo exposure of endrin on the activities of acid, alkaline and glucose-6-phosphatases in liver and kidney of Ophiocephalus (Channa) punctatus.", "content": "The effect of in vivo exposure of a sublethal concentration (0.01 mg/l) of endrin on the activities of acid, alkaline and glucose-6-phosphatases in the liver and kidney of Ophiccephalus punctatus was studied. The period of exposure was twenty days. In the liver, alkaline phosphatase and glucose-6-phosphatase activities were decreased but acid phosphatase was stimulated. Kidney showed stimulation in the activity of all the three phosphatases.", "contents": "The effect of in vivo exposure of endrin on the activities of acid, alkaline and glucose-6-phosphatases in liver and kidney of Ophiocephalus (Channa) punctatus. The effect of in vivo exposure of a sublethal concentration (0.01 mg/l) of endrin on the activities of acid, alkaline and glucose-6-phosphatases in the liver and kidney of Ophiccephalus punctatus was studied. The period of exposure was twenty days. In the liver, alkaline phosphatase and glucose-6-phosphatase activities were decreased but acid phosphatase was stimulated. Kidney showed stimulation in the activity of all the three phosphatases."}
{"id": "PMID:214194", "title": "Effects of calcium on acid secretion from the rat isolated gastric mucosa during stimulation with histamine, pentagastrin, methacholine and dibutyryl cyclic adenosine-3',5'-monophosphate.", "content": "1. An isolated gastric mucosal preparation from immature rats is described. The mucosal surface was superfused and acid secretion was recorded continuously by monitoring H+ -ion concentration. 2. Repeated stimulation with submaximal concentrations of histamine or dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP) produced consistent responses. Secretion induced by pentagastrin and methacholine demonstrated varying degrees of tachyphylaxis. All responses were readily reversed on washing out the secretagogue. 3. Reduction of Ca2+ from 3.6 mM increased responses to histamine, pentagastrin and methacholine while increase of Ca2+ to 7.2 mM decreased responses. Db cyclic AMP-induced secretion was not influenced by external Ca2+. 4. When Mg2+ was raised from 1.2 mM responses to histamine and pentagastrin increased. Replacement of Ca2+ with Mg2+ produced a transient increase followed by a decrease in responses. 5. The similarity of the effects of Ca2+ on pentagastrin, methacholine and histamine indicates that neither pentagastrin nor methacholine act via Ca2+ -dependent histamine release.", "contents": "Effects of calcium on acid secretion from the rat isolated gastric mucosa during stimulation with histamine, pentagastrin, methacholine and dibutyryl cyclic adenosine-3',5'-monophosphate. 1. An isolated gastric mucosal preparation from immature rats is described. The mucosal surface was superfused and acid secretion was recorded continuously by monitoring H+ -ion concentration. 2. Repeated stimulation with submaximal concentrations of histamine or dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP) produced consistent responses. Secretion induced by pentagastrin and methacholine demonstrated varying degrees of tachyphylaxis. All responses were readily reversed on washing out the secretagogue. 3. Reduction of Ca2+ from 3.6 mM increased responses to histamine, pentagastrin and methacholine while increase of Ca2+ to 7.2 mM decreased responses. Db cyclic AMP-induced secretion was not influenced by external Ca2+. 4. When Mg2+ was raised from 1.2 mM responses to histamine and pentagastrin increased. Replacement of Ca2+ with Mg2+ produced a transient increase followed by a decrease in responses. 5. The similarity of the effects of Ca2+ on pentagastrin, methacholine and histamine indicates that neither pentagastrin nor methacholine act via Ca2+ -dependent histamine release."}
{"id": "PMID:214198", "title": "Relation of high-density lipoprotein cholesterol concentration to type of diabetes and its control.", "content": "Serum cholesterol and high-density lipoprotein (HDL) cholesterol concentrations were measured in 192 diabetics (94 with juvenile-onset and 98 with maturity-onset diabetes) and 177 non-diabetic controls. Hb A1C, an index of blood sugar control, was also measured in the diabetics. Serum cholesterol concentrations were similar in all the diabetics and controls, but HDL cholesterol concentrations were lower in patients with maturity-onset diabetes than in those with juvenile-onset diabetes and controls. There was no correlation in diabetics between HDL cholesterol and Hb A1C. We conclude that HDL cholesterol concentrations are abnormally low in patients with maturity-onset diabetes but essentially normal in those with juvenile-onset diabetes. They are not related to diabetic control.", "contents": "Relation of high-density lipoprotein cholesterol concentration to type of diabetes and its control. Serum cholesterol and high-density lipoprotein (HDL) cholesterol concentrations were measured in 192 diabetics (94 with juvenile-onset and 98 with maturity-onset diabetes) and 177 non-diabetic controls. Hb A1C, an index of blood sugar control, was also measured in the diabetics. Serum cholesterol concentrations were similar in all the diabetics and controls, but HDL cholesterol concentrations were lower in patients with maturity-onset diabetes than in those with juvenile-onset diabetes and controls. There was no correlation in diabetics between HDL cholesterol and Hb A1C. We conclude that HDL cholesterol concentrations are abnormally low in patients with maturity-onset diabetes but essentially normal in those with juvenile-onset diabetes. They are not related to diabetic control."}
{"id": "PMID:214199", "title": "High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart diseae.", "content": "The serum concentration of high-density lipoprotein cholesterol and the proportion it constitutes of total serum cholesterol are high in children and low in sufferers from coronary heart disease (CHD). Studies in elderly black Africans in Western Transvaal showed them to be free of CHD. HDL concentrations measured at birth and in groups of 10- to 12-year-olds, 16- to 18-year olds, and 60- to 69-year-olds showed mean values of 0.96, 1.71, 1.58, and 1.94 mmol/l (36, 66, 61, and 65 mg/100 ml) respectively; these concentrations constitued about 56%, 54%, and 45%, and 47%, of total cholesterol. Values thus did not fall from youth to age as they did in whites. Rural South African blacks live on a diet high in fibre and low in animal protein and fat; children are active; and adults remain active even when old. These high values of HDL may well be representative for a population that is active, used to a frugal traditional diet, and free from CHD.", "contents": "High high-density-lipoprotein cholesterol in African children and adults in a population free of coronary heart diseae. The serum concentration of high-density lipoprotein cholesterol and the proportion it constitutes of total serum cholesterol are high in children and low in sufferers from coronary heart disease (CHD). Studies in elderly black Africans in Western Transvaal showed them to be free of CHD. HDL concentrations measured at birth and in groups of 10- to 12-year-olds, 16- to 18-year olds, and 60- to 69-year-olds showed mean values of 0.96, 1.71, 1.58, and 1.94 mmol/l (36, 66, 61, and 65 mg/100 ml) respectively; these concentrations constitued about 56%, 54%, and 45%, and 47%, of total cholesterol. Values thus did not fall from youth to age as they did in whites. Rural South African blacks live on a diet high in fibre and low in animal protein and fat; children are active; and adults remain active even when old. These high values of HDL may well be representative for a population that is active, used to a frugal traditional diet, and free from CHD."}
{"id": "PMID:214205", "title": "Interaction of morphine, etorphine and enkephalins with dopamine-stimulated adenylate cyclase of monkey amygdala.", "content": "Adenylate cyclase activity (AC) of homogenates of monkey amygdaloid nucleus was approximately doubled in the presence of dopamine (10 micrometer). Morphine, etorphine, and several enkephalin analogs (met-enkephalin, D-ala2-met-enkephalin, and D-met2, pro5-enkephalinamide) were capable of inhibiting the stimulation of AC produced by dopamine (90-100% with etorphine or D-ala2-met-enkephalin). Unlike morphine and etorphine, the peptides exhibited bell-shaped dose-response curves for this inhibition with maximal effects at approximately 1 X 10(-7) M, but negligible effects at 1 X 10(-5) M. Under the conditions studied, only etorphine inhibited basal AC. Naloxone antagonized the inhibitory effects of each of the opioids tested, and dextrorphan, an inactive L-(+)-opiate, failed to inhibit the dopamine response. Together these data indicate that the effects were mediated via the classically described stereospecific opiate receptor. The relative order of potency (etorphine greater than enkephalins greater than morphine) was similar to that previously reported for the binding affinities of these drugs in rat brain homogenates. The influence of narcotic agents on dopamine stimulated AC was eliminated by either freezing the amygdaloid tissue or preincubating the homogenate at 4 degrees C; the dopamine responses, however, could still be elicited. The narcotic receptor interaction with the adenylate cyclase thus appears to be distinct from and more labile than that of the dopamine receptor. Gpp(NH)p-stimulated AC was not inhibited by morphine. It is postulated that the inhibition involves interaction of opiate receptors with catalytic units of dopamine-stimulated AC, but not with other cyclase species which may provide the major component of Gpp(NH)p-stimulated activity in amygdala.", "contents": "Interaction of morphine, etorphine and enkephalins with dopamine-stimulated adenylate cyclase of monkey amygdala. Adenylate cyclase activity (AC) of homogenates of monkey amygdaloid nucleus was approximately doubled in the presence of dopamine (10 micrometer). Morphine, etorphine, and several enkephalin analogs (met-enkephalin, D-ala2-met-enkephalin, and D-met2, pro5-enkephalinamide) were capable of inhibiting the stimulation of AC produced by dopamine (90-100% with etorphine or D-ala2-met-enkephalin). Unlike morphine and etorphine, the peptides exhibited bell-shaped dose-response curves for this inhibition with maximal effects at approximately 1 X 10(-7) M, but negligible effects at 1 X 10(-5) M. Under the conditions studied, only etorphine inhibited basal AC. Naloxone antagonized the inhibitory effects of each of the opioids tested, and dextrorphan, an inactive L-(+)-opiate, failed to inhibit the dopamine response. Together these data indicate that the effects were mediated via the classically described stereospecific opiate receptor. The relative order of potency (etorphine greater than enkephalins greater than morphine) was similar to that previously reported for the binding affinities of these drugs in rat brain homogenates. The influence of narcotic agents on dopamine stimulated AC was eliminated by either freezing the amygdaloid tissue or preincubating the homogenate at 4 degrees C; the dopamine responses, however, could still be elicited. The narcotic receptor interaction with the adenylate cyclase thus appears to be distinct from and more labile than that of the dopamine receptor. Gpp(NH)p-stimulated AC was not inhibited by morphine. It is postulated that the inhibition involves interaction of opiate receptors with catalytic units of dopamine-stimulated AC, but not with other cyclase species which may provide the major component of Gpp(NH)p-stimulated activity in amygdala."}
{"id": "PMID:214210", "title": "A comparative study of ventrolateral and recurrent excitatory postsynaptic potentials in large pyramidal tract cells in the cat.", "content": "In acute cats deeply anesthetized with Nembutal, monosynaptic excitatory postsynaptic potentials (EPSPs) triggered by stimulation of the ventrolateral (VL) thalamic nucleus and the pes pedunculus were recorded in large pyramidal tract cells (PT cells). Deep anesthesia, low intensities of stimulation and an averaging technique were used in order to get VL and recurrent EPSPs free of polysynaptic potentials. Comparison of the time course of both EPSPs revealed a much faster rise time and shorter half-width for VL EPSPs than for recurrent EPSPs. This would suggest a more proximal location for VL synaptic contacts than for recurrent ones with respect to the soma of PT cells. The separation of the sites of origin of both EPSPs is further suggested by their almost perfect linear summation. It is suggested that VL EPSPs are produced on the apical dendritic tree, while recurrent EPSPs could originate on the basilar dendritic branches.", "contents": "A comparative study of ventrolateral and recurrent excitatory postsynaptic potentials in large pyramidal tract cells in the cat. In acute cats deeply anesthetized with Nembutal, monosynaptic excitatory postsynaptic potentials (EPSPs) triggered by stimulation of the ventrolateral (VL) thalamic nucleus and the pes pedunculus were recorded in large pyramidal tract cells (PT cells). Deep anesthesia, low intensities of stimulation and an averaging technique were used in order to get VL and recurrent EPSPs free of polysynaptic potentials. Comparison of the time course of both EPSPs revealed a much faster rise time and shorter half-width for VL EPSPs than for recurrent EPSPs. This would suggest a more proximal location for VL synaptic contacts than for recurrent ones with respect to the soma of PT cells. The separation of the sites of origin of both EPSPs is further suggested by their almost perfect linear summation. It is suggested that VL EPSPs are produced on the apical dendritic tree, while recurrent EPSPs could originate on the basilar dendritic branches."}
{"id": "PMID:214218", "title": "Chemotherapy studies in primary liver cancer: a prospective randomized clinical trial.", "content": "One hundred and sixty-eight patients with unresectable primary liver cancer were prospectively studied by members of the Eastern Cooperative Oncology Group. These patients were randomized to receive treatment with oral 5-Fluorouracil (5FU), oral 5-Fu plus Streptozotocin, oral 5-Fu plus Methyl-CCNU or Adriamycin. The single agent treatments (oral 5-Fu and Adriamycin) were associated with less gastrointestinal toxicity than were the oral 5-Fu treatment combinations. A total of 15 partial responses were reported. Adriamycin appears to be the most active agent and responsible for 9 of the 15 responses. No response was seen in any of the 48 patients randomized to oral 5-Fu alone. The survival associated with oral 5-Fu alone was significantly shorter than the survival time associated with the remaining 3 treatment programs among both North American and South African patients. A multivariate model of survival was formulated. Covariates of prognostic significance were treatment, initial performance status and sex. South African black patients had a shorter survival time than North American black patients. Excluding oral 5-Fu from consideration, prognostic variables appeared to dominate any differences between the remaining treatments under study.", "contents": "Chemotherapy studies in primary liver cancer: a prospective randomized clinical trial. One hundred and sixty-eight patients with unresectable primary liver cancer were prospectively studied by members of the Eastern Cooperative Oncology Group. These patients were randomized to receive treatment with oral 5-Fluorouracil (5FU), oral 5-Fu plus Streptozotocin, oral 5-Fu plus Methyl-CCNU or Adriamycin. The single agent treatments (oral 5-Fu and Adriamycin) were associated with less gastrointestinal toxicity than were the oral 5-Fu treatment combinations. A total of 15 partial responses were reported. Adriamycin appears to be the most active agent and responsible for 9 of the 15 responses. No response was seen in any of the 48 patients randomized to oral 5-Fu alone. The survival associated with oral 5-Fu alone was significantly shorter than the survival time associated with the remaining 3 treatment programs among both North American and South African patients. A multivariate model of survival was formulated. Covariates of prognostic significance were treatment, initial performance status and sex. South African black patients had a shorter survival time than North American black patients. Excluding oral 5-Fu from consideration, prognostic variables appeared to dominate any differences between the remaining treatments under study."}
{"id": "PMID:214219", "title": "Tubular carcinoma of the breast.", "content": "Retrospective pathologic review of 636 breast carcinomas from 611 patients revealed twelve tumors which were pure low grade tubular carcinoma (TC) and nineteen tumors with features combining both low grade tubular carcinoma and invasive duct carcinoma (T&D). A control group of 23 cases consisted of invasive duct carcinoma with at least a third of the tumor surface area showing tubular formation, but without the low grade features of tubular carcinoma. Life table analysis at 15 years showed a 100%, 72%, and 33% survival for TC, T&D, and controls, respectively. Eight percent of TC and 21% of T&D had axillary metastases compared to 67% for controls. Axillary metastases had no detrimental effect on TC or T&D survival. There were no recurrences in the TC group. Patients with T&D with tumor diameter 1.0 cm or less with 50% or greater low grade tubular carcinoma component are alive and well. The mean age of T&D was 7 years greater than TC. The combined TC and T&D group showed a significant incidence of multiple cancers in the ipsilateral breast and a significant trend toward bilateral cancers when compared to controls. Tubular carcinoma has an inherently low malignant potential with a histological and biological spectrum.", "contents": "Tubular carcinoma of the breast. Retrospective pathologic review of 636 breast carcinomas from 611 patients revealed twelve tumors which were pure low grade tubular carcinoma (TC) and nineteen tumors with features combining both low grade tubular carcinoma and invasive duct carcinoma (T&D). A control group of 23 cases consisted of invasive duct carcinoma with at least a third of the tumor surface area showing tubular formation, but without the low grade features of tubular carcinoma. Life table analysis at 15 years showed a 100%, 72%, and 33% survival for TC, T&D, and controls, respectively. Eight percent of TC and 21% of T&D had axillary metastases compared to 67% for controls. Axillary metastases had no detrimental effect on TC or T&D survival. There were no recurrences in the TC group. Patients with T&D with tumor diameter 1.0 cm or less with 50% or greater low grade tubular carcinoma component are alive and well. The mean age of T&D was 7 years greater than TC. The combined TC and T&D group showed a significant incidence of multiple cancers in the ipsilateral breast and a significant trend toward bilateral cancers when compared to controls. Tubular carcinoma has an inherently low malignant potential with a histological and biological spectrum."}
{"id": "PMID:214220", "title": "Biology of the human malignant lymphomas. IV. Functional characterization of ten diffuse histiocytic lymphoma cell lines.", "content": "Ten consecutive diffuse histiocytic lymphoma (DHL) cell lines established in our laboratory were studied for the presence of Epstein-Barr virus (EBV) genomes, lysozyme, nonspecific esterase and other cytochemical reactions, phagocytic activity, cytoplasmic immunoglobulin light and heavy chains, and surface receptors to sheep erythrocytes, complement, and the Fc fragment of immunoglobulin. In agreement with previous studies performed on biopsy specimens, our results indicate that the diffuse histiocytic lymphomas, as a histopathologic entity, represent a heterogeneous group of neoplasms, the majority of which are B-lymphocyte in origin. The cell lines appear to fall into three categories based on the following criteria: 1) presence of monoclonal cytoplasmic immunoglobulins (B-lymphocytic type, 6/10 cell lines); 2) presence of non-specific esterase, phagocytic activity, and/or lysozyme (histiocytic type, 2/10 cell lines); and 3) absence of all lymphoid and histiocytic cell characteristics (null cell type, 2/10 cell lines). Despite the fact that many of the lymphoma patients had positive serologies to EBV antigens, all of the DHL cell lines were negative for the presence of EBV genomes. Both of the two B-lymphocytic type and one of the two histiocytic type lines tested were susceptible to infection with EBV, as indicated by synthesis of early antigen and also, in a small proportion of the infected cells, of viral capsid antigen. These prototypic DHL cell lines may permit the development of new criteria for the differential diagnosis and treatment of this highly malignant and diverse group of lymphomas.", "contents": "Biology of the human malignant lymphomas. IV. Functional characterization of ten diffuse histiocytic lymphoma cell lines. Ten consecutive diffuse histiocytic lymphoma (DHL) cell lines established in our laboratory were studied for the presence of Epstein-Barr virus (EBV) genomes, lysozyme, nonspecific esterase and other cytochemical reactions, phagocytic activity, cytoplasmic immunoglobulin light and heavy chains, and surface receptors to sheep erythrocytes, complement, and the Fc fragment of immunoglobulin. In agreement with previous studies performed on biopsy specimens, our results indicate that the diffuse histiocytic lymphomas, as a histopathologic entity, represent a heterogeneous group of neoplasms, the majority of which are B-lymphocyte in origin. The cell lines appear to fall into three categories based on the following criteria: 1) presence of monoclonal cytoplasmic immunoglobulins (B-lymphocytic type, 6/10 cell lines); 2) presence of non-specific esterase, phagocytic activity, and/or lysozyme (histiocytic type, 2/10 cell lines); and 3) absence of all lymphoid and histiocytic cell characteristics (null cell type, 2/10 cell lines). Despite the fact that many of the lymphoma patients had positive serologies to EBV antigens, all of the DHL cell lines were negative for the presence of EBV genomes. Both of the two B-lymphocytic type and one of the two histiocytic type lines tested were susceptible to infection with EBV, as indicated by synthesis of early antigen and also, in a small proportion of the infected cells, of viral capsid antigen. These prototypic DHL cell lines may permit the development of new criteria for the differential diagnosis and treatment of this highly malignant and diverse group of lymphomas."}
{"id": "PMID:214221", "title": "Malignant fibrous histiocytoma of the heart presenting as an atrial myxoma.", "content": "A 37-year-old woman presented with signs and symptoms suggestive of mitral stenosis and insufficiency. Subsequent evaluation demonstrated a left atrial tumor which was suspected clinically and at the time of initial surgery to be an atrial myxoma. Histologic examination revealed that the tumor was actually a malignant fibrous histiocytoma. Despite near total removal at surgery and subsequent radiotherapy, the tumor recurred within six months in the left atrium. Re-excision was followed by a third recurrence in the same site.", "contents": "Malignant fibrous histiocytoma of the heart presenting as an atrial myxoma. A 37-year-old woman presented with signs and symptoms suggestive of mitral stenosis and insufficiency. Subsequent evaluation demonstrated a left atrial tumor which was suspected clinically and at the time of initial surgery to be an atrial myxoma. Histologic examination revealed that the tumor was actually a malignant fibrous histiocytoma. Despite near total removal at surgery and subsequent radiotherapy, the tumor recurred within six months in the left atrium. Re-excision was followed by a third recurrence in the same site."}
{"id": "PMID:214222", "title": "The clinical course and treatment results of patients with postresection locally recurrent lung cancer.", "content": "Of 1018 patients with lung cancer seen in the division of radiation therapy between 1963 and 1976, forty-six patients (4.5%) presented with postresection local recurrence and no documented distant metastasis. The median time to recurrence was thirteen months. Most patients had central recurrence with hilar or mediastinal lymph node metastasis, parenchymal consolidation, main stem nodule or bronchial stump tumor. There was a propensity for these tumors to remain limited to the site of origin. Death was most often from local/regional disease rather than distant metastasis. In this clinical setting the effectiveness of radiotherapy was observed in terms of palliation and improved survival. Strong determinants to survival were cell type, tumor dose and tumor response. The median survival was eleven months.", "contents": "The clinical course and treatment results of patients with postresection locally recurrent lung cancer. Of 1018 patients with lung cancer seen in the division of radiation therapy between 1963 and 1976, forty-six patients (4.5%) presented with postresection local recurrence and no documented distant metastasis. The median time to recurrence was thirteen months. Most patients had central recurrence with hilar or mediastinal lymph node metastasis, parenchymal consolidation, main stem nodule or bronchial stump tumor. There was a propensity for these tumors to remain limited to the site of origin. Death was most often from local/regional disease rather than distant metastasis. In this clinical setting the effectiveness of radiotherapy was observed in terms of palliation and improved survival. Strong determinants to survival were cell type, tumor dose and tumor response. The median survival was eleven months."}
{"id": "PMID:214226", "title": "Augmented immunogenicity of tumor cell membranes produced by infection with influenza virus as compared to Moloney sarcoma virus.", "content": "The tumor-associated transplantation antigens (TATA) of crude membrane extracts from SV40-transformed BALB/3T3 tumor cells lytically infected with influenza virus were markedly more immunogenic than were extracts from uninfected cells measured either by the ability to induce heightened resistance to tumorgraft challenge or by heightened lymphocyte-mediated cytotoxicity against tumor cells in vitro. When intact tumor cells (as opposed to membrane extracts) were productively infected with Moloney sarcoma virus, they were made so immunogenic that they would only grow in X-irradiated syngeneic animals. Yet crude membrane extracts from the Moloney sarcoma virus-infected tumor cells showed no increase in TATA activity analogous to that seen after infection with influenza virus. Thus, influenza virus augmentation of tumor membrane TATA may operate by a different mechanism than does the oncornavirus augmentation of intact tumor cell TATA reported by others. It appears that Moloney sarcoma virus and possibly other oncornaviruses cannot be used to augment the TATA activity of tumor cell membranes in the same way that other surface-budding viruses can.", "contents": "Augmented immunogenicity of tumor cell membranes produced by infection with influenza virus as compared to Moloney sarcoma virus. The tumor-associated transplantation antigens (TATA) of crude membrane extracts from SV40-transformed BALB/3T3 tumor cells lytically infected with influenza virus were markedly more immunogenic than were extracts from uninfected cells measured either by the ability to induce heightened resistance to tumorgraft challenge or by heightened lymphocyte-mediated cytotoxicity against tumor cells in vitro. When intact tumor cells (as opposed to membrane extracts) were productively infected with Moloney sarcoma virus, they were made so immunogenic that they would only grow in X-irradiated syngeneic animals. Yet crude membrane extracts from the Moloney sarcoma virus-infected tumor cells showed no increase in TATA activity analogous to that seen after infection with influenza virus. Thus, influenza virus augmentation of tumor membrane TATA may operate by a different mechanism than does the oncornavirus augmentation of intact tumor cell TATA reported by others. It appears that Moloney sarcoma virus and possibly other oncornaviruses cannot be used to augment the TATA activity of tumor cell membranes in the same way that other surface-budding viruses can."}
{"id": "PMID:214228", "title": "Synergistic effect of tumor virus transformation and tumor promoter treatment on the production of plasminogen activator by chick embryo fibroblasts.", "content": "Cultures of Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF) produce 50-fold more of the protease plasminogen activator (PA), than do normal chick embryo fibroblasts. Treatment of RSVCEF cultures with the tumor promoter phorbol myristate acetate (PMA) further enhances (8- to 12-fold) the level of PA activity. Increased levels of PA activity in RSVCEF are observed as early as 1 to 2 hr after PMA treatment. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrates that the PA produced by PMA-treated cultures has a molecular weight identical to that of the PA produced by untreated cultures. PA induction by PMA cannot be accomplished in cell-free extracts, but requires protein synthesis in intact cells. Under serum-free conditions, PMA-treated RSVCEF secrete high levels of PA for 4 to 6 days and undergo pronounced morphological alterations. Modified culture conditions and the use of PMA to induce PA has allowed for the accumulation of large amounts of RSVCEF culture fluid and the subsequent purification of the enzyme. The sensitivity of transformed CEF to PMA and the generation of enhanced proteolytic activity in the cellular microenvironment may provide a model system to examine the role of both PA in malignant transformation and PMA in tumor promotion.", "contents": "Synergistic effect of tumor virus transformation and tumor promoter treatment on the production of plasminogen activator by chick embryo fibroblasts. Cultures of Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF) produce 50-fold more of the protease plasminogen activator (PA), than do normal chick embryo fibroblasts. Treatment of RSVCEF cultures with the tumor promoter phorbol myristate acetate (PMA) further enhances (8- to 12-fold) the level of PA activity. Increased levels of PA activity in RSVCEF are observed as early as 1 to 2 hr after PMA treatment. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrates that the PA produced by PMA-treated cultures has a molecular weight identical to that of the PA produced by untreated cultures. PA induction by PMA cannot be accomplished in cell-free extracts, but requires protein synthesis in intact cells. Under serum-free conditions, PMA-treated RSVCEF secrete high levels of PA for 4 to 6 days and undergo pronounced morphological alterations. Modified culture conditions and the use of PMA to induce PA has allowed for the accumulation of large amounts of RSVCEF culture fluid and the subsequent purification of the enzyme. The sensitivity of transformed CEF to PMA and the generation of enhanced proteolytic activity in the cellular microenvironment may provide a model system to examine the role of both PA in malignant transformation and PMA in tumor promotion."}
{"id": "PMID:214230", "title": "Isozymes of pyruvate kinase from human brain, meningiomas, and malignant gliomas.", "content": "Pyruvate kinase isozymes were studied in normal brain tissue (both fetal and adult) and in meningiomas and malignant gliomas. In fetal brain five different forms could be detected by electrophoresis (K4, K3M, K2M2, KM3, and M4). In adult brain the M4-type, K3M hybrid, and K4-type are present; the M isozyme is largely predominant. Alanine inhibition of pyruvate kinase is in agreement with the electrophoretic pattern. Pyruvate kinase from fetal brain and brain of a newborn is more inhibited compared with pyruvate kinase from adult brain. The Lineweaver-Burk plots for pyruvate kinase from fetal brain and brain of the newborn are nonlinear due to the presence of hybrids. Pyruvate kinase from meningiomas and malignant gliomas is strongly inhibited by alanine. Electrophoresis proved the presence of mainly K4 type and the hybrid K3M, which is in agreement with the alanine inhibition. Determination of the Km's for phosphoenolpyruvate supports this conclusion. The determination of the alanine inhibition of pyruvate kinase may be a diagnostic tool in surgery for gliomas.", "contents": "Isozymes of pyruvate kinase from human brain, meningiomas, and malignant gliomas. Pyruvate kinase isozymes were studied in normal brain tissue (both fetal and adult) and in meningiomas and malignant gliomas. In fetal brain five different forms could be detected by electrophoresis (K4, K3M, K2M2, KM3, and M4). In adult brain the M4-type, K3M hybrid, and K4-type are present; the M isozyme is largely predominant. Alanine inhibition of pyruvate kinase is in agreement with the electrophoretic pattern. Pyruvate kinase from fetal brain and brain of a newborn is more inhibited compared with pyruvate kinase from adult brain. The Lineweaver-Burk plots for pyruvate kinase from fetal brain and brain of the newborn are nonlinear due to the presence of hybrids. Pyruvate kinase from meningiomas and malignant gliomas is strongly inhibited by alanine. Electrophoresis proved the presence of mainly K4 type and the hybrid K3M, which is in agreement with the alanine inhibition. Determination of the Km's for phosphoenolpyruvate supports this conclusion. The determination of the alanine inhibition of pyruvate kinase may be a diagnostic tool in surgery for gliomas."}
{"id": "PMID:214231", "title": "Suppressive effects on simian virus 40-induced oncogenesis of several immunosuppressive agents and hormonal modifications applied during the latent period.", "content": "The long latent period required for tumor induction with Simian virus 40 (SV40) in the subcutis of hamsters can be used to investigate whether host factor(s) participate in oncogenesis. Several treatments were applied during this period, and the results were compared with those of the same treatment applied in another series of experiments, homologous SV40 tumor grafting in hamsters. The results obtained were as follows: (a) the latent period for SV40 tumor induction in the female was shorter than that in the male; tumor development was delayed significantly by oophorectomy but was little affected by orchiectomy. Tumor development was markedly delayed in animals of both sexes by estrone given at birth but was accelerated by testosterone given in the adult male; (b) by each of these hormonal modifications, growth of transplanted SV40 tumors was influenced in a different way from that of tumor induction; (c) immunosuppressive treatments, such as thymectomy, administration of antilymphocyte sera, cyclophosphamide, or cortisone acetate delayed and decreased tumor development when applied in the latent period, and the degree or pattern of this effect varied from one procedure to another, depending on the sex and age of the animals; (d) in contrast, tumor growth was markedly accelerated in thymectomized or cortisone-treated hosts irrespective of sex. The different and almost reverse effect of the same procedure in the two phases of tumorigenesis may indicate two discriminating mechanisms operating in the host during these phases. This different effect may be due to virtual absence of any \"mature\" neoplastic cell in the latent period, except for a few weeks before the appearance of a palpable tumor. These results suggest that the long period of latency may be spent to complete SV40-induced neoplastic conversion of cells, receiving some help by host factors.", "contents": "Suppressive effects on simian virus 40-induced oncogenesis of several immunosuppressive agents and hormonal modifications applied during the latent period. The long latent period required for tumor induction with Simian virus 40 (SV40) in the subcutis of hamsters can be used to investigate whether host factor(s) participate in oncogenesis. Several treatments were applied during this period, and the results were compared with those of the same treatment applied in another series of experiments, homologous SV40 tumor grafting in hamsters. The results obtained were as follows: (a) the latent period for SV40 tumor induction in the female was shorter than that in the male; tumor development was delayed significantly by oophorectomy but was little affected by orchiectomy. Tumor development was markedly delayed in animals of both sexes by estrone given at birth but was accelerated by testosterone given in the adult male; (b) by each of these hormonal modifications, growth of transplanted SV40 tumors was influenced in a different way from that of tumor induction; (c) immunosuppressive treatments, such as thymectomy, administration of antilymphocyte sera, cyclophosphamide, or cortisone acetate delayed and decreased tumor development when applied in the latent period, and the degree or pattern of this effect varied from one procedure to another, depending on the sex and age of the animals; (d) in contrast, tumor growth was markedly accelerated in thymectomized or cortisone-treated hosts irrespective of sex. The different and almost reverse effect of the same procedure in the two phases of tumorigenesis may indicate two discriminating mechanisms operating in the host during these phases. This different effect may be due to virtual absence of any \"mature\" neoplastic cell in the latent period, except for a few weeks before the appearance of a palpable tumor. These results suggest that the long period of latency may be spent to complete SV40-induced neoplastic conversion of cells, receiving some help by host factors."}
{"id": "PMID:214234", "title": "Studies on secretory glycoproteins in the rat exocrine pancreas. III. Intracellular transport of fucose-labeled proteins as studied by cell fractionation.", "content": "The transcellular movement of fucosylated glycoproteins has been studied in vitro using rat pancreatic lobules and cell fractionation procedures, and has been compared with the well established pathway of secretory proteins. Using tritiated leucine as pulse label for the latter, their translocation from the rough endoplasmatic reticulum into the Golgi complex and finally into zymogen granules could be followed. In the case of glycoproteins, 14C-fucose was incorporated mainly into the smooth microsomal fraction (representative of the Golgi complex) and only one third of this specific activity was transported into the zymogen granule fraction. A detailed analysis of this fraction after separation of the content of zymogen granules from their membranes revealed a predominant labeling of membrane glycoproteins by 14C-fucose. In comparison, leucine-labeled bulk proteins were found almost exclusively in the zymogen granule content fraction, with little radioactivity in the membrane fraction. The data indicate a concomitant synthesis of fucosylated glycoproteins destined in part for the zymogen granule membrane and to a greater amount associated with the smooth microsomal fraction. The results are discussed in the light of recent findings indicating that about 40% of the proteins in the zymogen granule membrane are made up of one major glycoprotein which could be involved in the mechanism of exocytosis.", "contents": "Studies on secretory glycoproteins in the rat exocrine pancreas. III. Intracellular transport of fucose-labeled proteins as studied by cell fractionation. The transcellular movement of fucosylated glycoproteins has been studied in vitro using rat pancreatic lobules and cell fractionation procedures, and has been compared with the well established pathway of secretory proteins. Using tritiated leucine as pulse label for the latter, their translocation from the rough endoplasmatic reticulum into the Golgi complex and finally into zymogen granules could be followed. In the case of glycoproteins, 14C-fucose was incorporated mainly into the smooth microsomal fraction (representative of the Golgi complex) and only one third of this specific activity was transported into the zymogen granule fraction. A detailed analysis of this fraction after separation of the content of zymogen granules from their membranes revealed a predominant labeling of membrane glycoproteins by 14C-fucose. In comparison, leucine-labeled bulk proteins were found almost exclusively in the zymogen granule content fraction, with little radioactivity in the membrane fraction. The data indicate a concomitant synthesis of fucosylated glycoproteins destined in part for the zymogen granule membrane and to a greater amount associated with the smooth microsomal fraction. The results are discussed in the light of recent findings indicating that about 40% of the proteins in the zymogen granule membrane are made up of one major glycoprotein which could be involved in the mechanism of exocytosis."}
{"id": "PMID:214235", "title": "Intranuclear inclusions in pericytes of the hypothalamus of the rat.", "content": "This paper deals with the ultrastructure of two types of intranuclear inclusions, \"nuclear bodies\" and \"membranous lamellar bodies\", present in hypothalamic pericytes of intact adult rats. The nuclear bodies exhibited \"simple\" and \"granular\" forms, whereas the membranous lamellar bodies were entirely made up of myelin-like membrane whorls. The occurrence of these bodies in nuclei of pericytes has never been previously reported. The origin and functional meaning of such structures is discussed in the light of recent ultrastructural and biochemical studies on nuclear inclusions.", "contents": "Intranuclear inclusions in pericytes of the hypothalamus of the rat. This paper deals with the ultrastructure of two types of intranuclear inclusions, \"nuclear bodies\" and \"membranous lamellar bodies\", present in hypothalamic pericytes of intact adult rats. The nuclear bodies exhibited \"simple\" and \"granular\" forms, whereas the membranous lamellar bodies were entirely made up of myelin-like membrane whorls. The occurrence of these bodies in nuclei of pericytes has never been previously reported. The origin and functional meaning of such structures is discussed in the light of recent ultrastructural and biochemical studies on nuclear inclusions."}
{"id": "PMID:214237", "title": "Plasminogen activator in chick fibroblasts: induction of synthesis by retinoic acid; synergism with viral transformation and phorbol ester.", "content": "This paper reports the effect of vitamin A and its derivatives, the retinoids, on plasminogen activator (PA) synthesis in chick embryo fibroblast cultures (CEF). Low concentrations of retinoic acid (RA) (10(-6)-10(-10) M) and the retinoids stimulated PA synthesis in CEF; the maximal stimulation achieved, 9--10 fold, was somewhat lower than that obtained with optimal concentrations of the potent tumor promoter phorbol myristate acetate (PMA). This action of RA required protein and mRNA synthesis but, in contrast to enzyme induction by PMA and/or sarcoma virus transformation, retinoid effects were not significantly inhibited by elevated concentrations of cAMP. In inducing and/or stimulating PA production, the effects of RA and sarcoma virus transformation were synergistic rather than additive. Analogous synergism was observed between RA and PMA, but only at suboptimal concentrations of the latter. RA did not affect PA production in normal or transformed cultures maximally stimulated by PMA. These findings may help to elucidate the role of retinoids in promoting tumor growth, tissue remodeling and teratogenesis.", "contents": "Plasminogen activator in chick fibroblasts: induction of synthesis by retinoic acid; synergism with viral transformation and phorbol ester. This paper reports the effect of vitamin A and its derivatives, the retinoids, on plasminogen activator (PA) synthesis in chick embryo fibroblast cultures (CEF). Low concentrations of retinoic acid (RA) (10(-6)-10(-10) M) and the retinoids stimulated PA synthesis in CEF; the maximal stimulation achieved, 9--10 fold, was somewhat lower than that obtained with optimal concentrations of the potent tumor promoter phorbol myristate acetate (PMA). This action of RA required protein and mRNA synthesis but, in contrast to enzyme induction by PMA and/or sarcoma virus transformation, retinoid effects were not significantly inhibited by elevated concentrations of cAMP. In inducing and/or stimulating PA production, the effects of RA and sarcoma virus transformation were synergistic rather than additive. Analogous synergism was observed between RA and PMA, but only at suboptimal concentrations of the latter. RA did not affect PA production in normal or transformed cultures maximally stimulated by PMA. These findings may help to elucidate the role of retinoids in promoting tumor growth, tissue remodeling and teratogenesis."}
{"id": "PMID:214238", "title": "The induction of differentiation in teratocarcinoma stem cells by retinoic acid.", "content": "Embryonal carcinoma cells, the stem cells of teratocarcinomas, usually undergo extensive differentiation in vivo and in vitro to a wide variety of cell types. There exist, however, several embryonal carcinoma cell lines that have almost completely lost the capacity to differentiate, so that the cells are propagated primarily as the stem cells. Using one such cell line, F9, we have found that retinoic acid at concentrations as low as 10(-9) M induces multiple phenotypic changes in the cultures in vitro. These changes include morphological alteration at the resolution of the light microscope, elevated levels of plasminogen activator production, sensitivity to cyclic AMP compounds and increased synthesis of collagen-like proteins. The nature of these changes, as well as their independence of the continued presence of retinoic acid, are consistent with the proposition that retinoic acid induces differentiation of embryonal carcinoma cells into endoderm.", "contents": "The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Embryonal carcinoma cells, the stem cells of teratocarcinomas, usually undergo extensive differentiation in vivo and in vitro to a wide variety of cell types. There exist, however, several embryonal carcinoma cell lines that have almost completely lost the capacity to differentiate, so that the cells are propagated primarily as the stem cells. Using one such cell line, F9, we have found that retinoic acid at concentrations as low as 10(-9) M induces multiple phenotypic changes in the cultures in vitro. These changes include morphological alteration at the resolution of the light microscope, elevated levels of plasminogen activator production, sensitivity to cyclic AMP compounds and increased synthesis of collagen-like proteins. The nature of these changes, as well as their independence of the continued presence of retinoic acid, are consistent with the proposition that retinoic acid induces differentiation of embryonal carcinoma cells into endoderm."}
{"id": "PMID:214239", "title": "Fv-1 regulation of lymphoma development and of thymic ecotropic and xenotropic MuLV expression in mice of the AKR/J x RF/J cross.", "content": "The incidence of spontaneous thymic lymphoma has been studied in crosses between AKR/J and RF/J mice. AKR mice develop a high incidence of this disease. RF mice transmit a marked resistance to development of the disease to F1 hybrid mice of the AKR x RF cross. This resistance is associated with a reduction of endogenous ecotropic and xenotropic MuLV expression in the prelymphomatous thymus. The RF gene governing the coordinate suppression of these three phenotypes has been mapped to the Fv-1 locus. These results indicate that the particular Fv-1 allele of AKR mice provides a permissive genetic background for endogenous ecotropic and xenotropic MuLV expression and that these viral activities may be etiologically involved in the development of spontaneous thymic lymphoma in the mouse.", "contents": "Fv-1 regulation of lymphoma development and of thymic ecotropic and xenotropic MuLV expression in mice of the AKR/J x RF/J cross. The incidence of spontaneous thymic lymphoma has been studied in crosses between AKR/J and RF/J mice. AKR mice develop a high incidence of this disease. RF mice transmit a marked resistance to development of the disease to F1 hybrid mice of the AKR x RF cross. This resistance is associated with a reduction of endogenous ecotropic and xenotropic MuLV expression in the prelymphomatous thymus. The RF gene governing the coordinate suppression of these three phenotypes has been mapped to the Fv-1 locus. These results indicate that the particular Fv-1 allele of AKR mice provides a permissive genetic background for endogenous ecotropic and xenotropic MuLV expression and that these viral activities may be etiologically involved in the development of spontaneous thymic lymphoma in the mouse."}
{"id": "PMID:214240", "title": "A herpes simplex virus 1 integration site in the mouse genome defined by somatic cell genetic analysis.", "content": "Transfection experiments with HSV 1 in which one uses herpes simplex virus (HSV) thymidine kinase (TK) as a selectable prototrophic marker yield two classes of transformed cells: stable and unstable. In this report, we test the hypothesis that the stability phenotype can be explained by virus genome integration into a recipient cell chromosome. The method of analysis is by means of somatic cell genetics. We have isolated a series of microcell hybrids between a TK- Chinese hamster cell line and a transformed mouse cell line expressing the TK encoded by HSV 1. Several of the hybrid lines contain a single murine chromosome and express only the viral TK. Karyotypic analysis of these hybrids and of TK- derivatives generated by BrdUrd counterselection reveals that the TK+ phenotype is correlated with the presence of the terminal portion of the long arm of a specific murine chromosome. Results of extensive isozyme analyses of the hybrids and their TK- segregants fully corroborate the karyologic data. The results are consistent with the hypothesis that the viral tk gene is covalently integrated into this chromosomal region which itself does not appear to carry the endogenous murine tk locus. Other more complicated models are discussed. Our findings also show that somatic cell genetics can be used to localize viral integration sites in host chromosomes with high resolution.", "contents": "A herpes simplex virus 1 integration site in the mouse genome defined by somatic cell genetic analysis. Transfection experiments with HSV 1 in which one uses herpes simplex virus (HSV) thymidine kinase (TK) as a selectable prototrophic marker yield two classes of transformed cells: stable and unstable. In this report, we test the hypothesis that the stability phenotype can be explained by virus genome integration into a recipient cell chromosome. The method of analysis is by means of somatic cell genetics. We have isolated a series of microcell hybrids between a TK- Chinese hamster cell line and a transformed mouse cell line expressing the TK encoded by HSV 1. Several of the hybrid lines contain a single murine chromosome and express only the viral TK. Karyotypic analysis of these hybrids and of TK- derivatives generated by BrdUrd counterselection reveals that the TK+ phenotype is correlated with the presence of the terminal portion of the long arm of a specific murine chromosome. Results of extensive isozyme analyses of the hybrids and their TK- segregants fully corroborate the karyologic data. The results are consistent with the hypothesis that the viral tk gene is covalently integrated into this chromosomal region which itself does not appear to carry the endogenous murine tk locus. Other more complicated models are discussed. Our findings also show that somatic cell genetics can be used to localize viral integration sites in host chromosomes with high resolution."}
{"id": "PMID:214241", "title": "Tumor antigens induced by nontransforming mutants of polyoma virus.", "content": "We have studied the tumor (T) antigens induced by wild-type polyoma virus and several nontransforming mutants using immunoprecipitation with antisera from animals bearing polyomya-induced tumors followed by sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis. In a variety of mouse cells, wild-type virus induces a major T antigen species with apparent molecular weight of 100,000 daltons, and four minor T antigen species with apparent molecular weights of 63,000, 56,000, 36,000 and 22,000 daltons. Hr-t mutants, which have an absolute defect in transformation, induce a normal 100,000 dalton T antigen but are altered in the minor T antigen species. Hr-t deletion mutants induce none of the minor T antigen species seen in wild-type virus. In their place, these mutants induce T antigen species with molecular weights in the range of 6,000--9,000 daltons. The size of the very small T antigen products does not correlate in any simple way with the size or location of the deletions in the viral DNA. Point hr-t mutants induce two of the four minor T antigen species; they make apparently normal amounts of the 56,000 dalton product and reduced amounts of the 22,000 dalton product, but none of the 63,000 or 36,000 dalton species. Ts-a mutants, which have a temperature-sensitive defect in the ability to induce stable transformation, and which complement hr-t mutants, induce T antigens with the same mobility as wild-type; however, the 100,000 dalton T antigen of ts-a mutants is thermolabile compared to wild-type. A double mutant virus carrying both a ts-a mutation and a deletion hr-t mutation induces a thermolabile 100,000 dalton product and none of the minor T antigen species. Cell fractionation studies with productively infected cells have been carried out to localize the T antigen species.", "contents": "Tumor antigens induced by nontransforming mutants of polyoma virus. We have studied the tumor (T) antigens induced by wild-type polyoma virus and several nontransforming mutants using immunoprecipitation with antisera from animals bearing polyomya-induced tumors followed by sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis. In a variety of mouse cells, wild-type virus induces a major T antigen species with apparent molecular weight of 100,000 daltons, and four minor T antigen species with apparent molecular weights of 63,000, 56,000, 36,000 and 22,000 daltons. Hr-t mutants, which have an absolute defect in transformation, induce a normal 100,000 dalton T antigen but are altered in the minor T antigen species. Hr-t deletion mutants induce none of the minor T antigen species seen in wild-type virus. In their place, these mutants induce T antigen species with molecular weights in the range of 6,000--9,000 daltons. The size of the very small T antigen products does not correlate in any simple way with the size or location of the deletions in the viral DNA. Point hr-t mutants induce two of the four minor T antigen species; they make apparently normal amounts of the 56,000 dalton product and reduced amounts of the 22,000 dalton product, but none of the 63,000 or 36,000 dalton species. Ts-a mutants, which have a temperature-sensitive defect in the ability to induce stable transformation, and which complement hr-t mutants, induce T antigens with the same mobility as wild-type; however, the 100,000 dalton T antigen of ts-a mutants is thermolabile compared to wild-type. A double mutant virus carrying both a ts-a mutation and a deletion hr-t mutation induces a thermolabile 100,000 dalton product and none of the minor T antigen species. Cell fractionation studies with productively infected cells have been carried out to localize the T antigen species."}
{"id": "PMID:214242", "title": "Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein.", "content": "Avian sarcoma virus (ASV) induces sarcomas in animals and transforms fibroblasts to a neoplastic state in cell culture. A single viral gene (src) is responsible for both the induction and maintenance of neoplastic transformation. Recent work has identified a protein with a molecular weight of 60,000 daltons that is apparently encoded in src and may be the effector molecule for the gene (Brugge and Erikson, 1977; Purchio et al, 1978). The putative product of src can be immunoprecipitated by antisera obtained from rabbits bearing tumors induced by ASV. We have used this approach to isolate the protein to characterize further its genetic origins and possible function. Our rabbit tumor antisera precipitated a protein with a molecular weight of 60,000 daltons; according to serological, biochemical and genetic criteria, this protein is encoded in src. We found that this protein is phosphorylated and therefore denoted it pp60. Phosphorylation of pp60 could be accomplished in vitro with extracts of ASV-infected cells. A temperature-sensitive conditional mutation in src had no demonstrable effect on either the production or stability of pp60 in the infected cell, but phosphorylation of the protein was temperature-sensitive. Since the mutant src is not expressed at the restrictive temperature, our findings raise the possibility that phosphorylation of pp60 is required for its function as the putative effector of src. Immunoprecipitates prepared with extracts of ASV-infected cells and the rabbit tumor antisera contained a protein kinase activity that catalyzed phosphorylation of the heavy chains of immunoglobulin molecules, using either ATP or GTP as phosphate donor. The kinase activity immunoprecipitated in parallel with pp60 was obtained only from cells that contained a functioning product of src and could not be precipitated with antisera directed against structural proteins of ASV. A temperature-sensitive conditional mutation in src caused the kinase activity to be thermally inactivated in vitro far more rapidly than the activity from cells infected with wild-type virus. We conclude that both the protein kinase and pp60 are encoded in src, and that the enzymatic activity may be an intrinsic property of pp60. Phosphorylation of pp60 in cellular extracts was inhibited by calcium ion, whereas the immunoprecipitable kinase activity was not, suggesting that the kinase responsible for pp60 phosphorylation may be distinct from that encoded in src. Collett  and Erikson (1978) have also identified a protein kinase activity associated with pp60. These findings raise the possibility that phosphorylation of specific cellular targets might account for transformation of the host cell by src.", "contents": "Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. Avian sarcoma virus (ASV) induces sarcomas in animals and transforms fibroblasts to a neoplastic state in cell culture. A single viral gene (src) is responsible for both the induction and maintenance of neoplastic transformation. Recent work has identified a protein with a molecular weight of 60,000 daltons that is apparently encoded in src and may be the effector molecule for the gene (Brugge and Erikson, 1977; Purchio et al, 1978). The putative product of src can be immunoprecipitated by antisera obtained from rabbits bearing tumors induced by ASV. We have used this approach to isolate the protein to characterize further its genetic origins and possible function. Our rabbit tumor antisera precipitated a protein with a molecular weight of 60,000 daltons; according to serological, biochemical and genetic criteria, this protein is encoded in src. We found that this protein is phosphorylated and therefore denoted it pp60. Phosphorylation of pp60 could be accomplished in vitro with extracts of ASV-infected cells. A temperature-sensitive conditional mutation in src had no demonstrable effect on either the production or stability of pp60 in the infected cell, but phosphorylation of the protein was temperature-sensitive. Since the mutant src is not expressed at the restrictive temperature, our findings raise the possibility that phosphorylation of pp60 is required for its function as the putative effector of src. Immunoprecipitates prepared with extracts of ASV-infected cells and the rabbit tumor antisera contained a protein kinase activity that catalyzed phosphorylation of the heavy chains of immunoglobulin molecules, using either ATP or GTP as phosphate donor. The kinase activity immunoprecipitated in parallel with pp60 was obtained only from cells that contained a functioning product of src and could not be precipitated with antisera directed against structural proteins of ASV. A temperature-sensitive conditional mutation in src caused the kinase activity to be thermally inactivated in vitro far more rapidly than the activity from cells infected with wild-type virus. We conclude that both the protein kinase and pp60 are encoded in src, and that the enzymatic activity may be an intrinsic property of pp60. Phosphorylation of pp60 in cellular extracts was inhibited by calcium ion, whereas the immunoprecipitable kinase activity was not, suggesting that the kinase responsible for pp60 phosphorylation may be distinct from that encoded in src. Collett  and Erikson (1978) have also identified a protein kinase activity associated with pp60. These findings raise the possibility that phosphorylation of specific cellular targets might account for transformation of the host cell by src."}
{"id": "PMID:214243", "title": "Linkage of the endogenous avian leukosis virus genome of virus-producing chicken cells to inhibitory cellular DNA sequences.", "content": "The endogenous avian leukosis virus genome of uninfected virus-producing(V+) chicken embryo fibroblasts appears to be inefficiently transcribed and is noninfectious in transfection assays of high molecular weight DNA. We previously proposed that the endogenous virus genome was linked to a cis-acting control element which inhibited its transcription and, consequently, interfered with transfection by endogenous viral DNA. We now report that DNA of uninfected V+ cells is infectious at a low level when sheared to the approximate size of the virus genome. These results suggest that the endogenous virus genome of uninfected V+ chicken cells can be converted to an infectious form by separating it from adjacent cellular DNA sequences, as predicted by the cis-acting control element model.", "contents": "Linkage of the endogenous avian leukosis virus genome of virus-producing chicken cells to inhibitory cellular DNA sequences. The endogenous avian leukosis virus genome of uninfected virus-producing(V+) chicken embryo fibroblasts appears to be inefficiently transcribed and is noninfectious in transfection assays of high molecular weight DNA. We previously proposed that the endogenous virus genome was linked to a cis-acting control element which inhibited its transcription and, consequently, interfered with transfection by endogenous viral DNA. We now report that DNA of uninfected V+ cells is infectious at a low level when sheared to the approximate size of the virus genome. These results suggest that the endogenous virus genome of uninfected V+ chicken cells can be converted to an infectious form by separating it from adjacent cellular DNA sequences, as predicted by the cis-acting control element model."}
{"id": "PMID:214244", "title": "Mapping of early SV40-specific functions by microinjection of different early viral DNA fragments.", "content": "DNA sequences within the early simian virus 40 (SV40) genome region responsible for virus-specific tumor (T) and U antigenicity, stimulation of cell DNA synthesis, initiation of late SV40 gene expression and helper function for human adenovirus 2 were confined by experiments using microinjection of different early SV40 DNA fragments. All these early functions were detected in cells supplied with complete early viral information. Cells microinjected with DNA fragments containing about 80, 70 or 60% of thea early SV40 genome were still stained positively when challenged with antibody against T antigen, and the same cells were stimulated for cellular DNA synthesis when about 70% or more of the early viral information was available. DNA sequences at map position 0.67 are required for intracellular early viral transcription.", "contents": "Mapping of early SV40-specific functions by microinjection of different early viral DNA fragments. DNA sequences within the early simian virus 40 (SV40) genome region responsible for virus-specific tumor (T) and U antigenicity, stimulation of cell DNA synthesis, initiation of late SV40 gene expression and helper function for human adenovirus 2 were confined by experiments using microinjection of different early SV40 DNA fragments. All these early functions were detected in cells supplied with complete early viral information. Cells microinjected with DNA fragments containing about 80, 70 or 60% of thea early SV40 genome were still stained positively when challenged with antibody against T antigen, and the same cells were stimulated for cellular DNA synthesis when about 70% or more of the early viral information was available. DNA sequences at map position 0.67 are required for intracellular early viral transcription."}
{"id": "PMID:214245", "title": "Intervening polyadenylate sequences in RNA transcripts of vesicular stomatitis virus.", "content": "Purified and partially resolved vesicular stomatitis virus (VSV) messenger RNA has been annealed to the VSV genomic RNA and visualized in the electron microscope under conditions in which duplex regions have a wider image width than single-stranded RNA. The locations of the intercistronic boundaries between the messages have been mapped on the VSV genome. The contour of the double-stranded regions is occasionally interrupted by looped-out single-stranded RNA. The loops are comprised of post transcriptionally synthesized polyadenylate. Most of these structures are found at the intercistronic boundaries and covalently bridge adjacent message sequences. In this paper, we discuss the possible significance of these loops.", "contents": "Intervening polyadenylate sequences in RNA transcripts of vesicular stomatitis virus. Purified and partially resolved vesicular stomatitis virus (VSV) messenger RNA has been annealed to the VSV genomic RNA and visualized in the electron microscope under conditions in which duplex regions have a wider image width than single-stranded RNA. The locations of the intercistronic boundaries between the messages have been mapped on the VSV genome. The contour of the double-stranded regions is occasionally interrupted by looped-out single-stranded RNA. The loops are comprised of post transcriptionally synthesized polyadenylate. Most of these structures are found at the intercistronic boundaries and covalently bridge adjacent message sequences. In this paper, we discuss the possible significance of these loops."}
{"id": "PMID:214250", "title": "Studies on the reduction of nitroblue tetrazolium chloride mediated through the action of NADH and phenazine methosulphate.", "content": "The general features of the reduction of nitroblue tetrazolium chloride (NBT) by NADH and phenazine methosulphate (PMS) have been studied under aerobic and anaerobic conditions. Under aerobic condition the reduction appears to be mediated through the intermediate formation of the superoxide anion radical O2-.; this reaction is strongly inhibited by superoxide dismutase and by a number of O2-. scavengers such as propyl gallate, (+)-catechin, manganous ions, reduced glutathione and benzoquinone. Cupric ions inhibited the overall reaction by reoxidising reduced PMS. Under anaerobic conditions, superoxide dismutase had only a small inhibitory action and, with the exception of cupric ions, the other substances mentioned above were ineffective as inhibitors. The data presented show that the use of NBT to detect the presence of O2-. is fraught with difficulties due to an equally rapid reduction of NBT by NADH and PMS under anaerobic conditions.", "contents": "Studies on the reduction of nitroblue tetrazolium chloride mediated through the action of NADH and phenazine methosulphate. The general features of the reduction of nitroblue tetrazolium chloride (NBT) by NADH and phenazine methosulphate (PMS) have been studied under aerobic and anaerobic conditions. Under aerobic condition the reduction appears to be mediated through the intermediate formation of the superoxide anion radical O2-.; this reaction is strongly inhibited by superoxide dismutase and by a number of O2-. scavengers such as propyl gallate, (+)-catechin, manganous ions, reduced glutathione and benzoquinone. Cupric ions inhibited the overall reaction by reoxidising reduced PMS. Under anaerobic conditions, superoxide dismutase had only a small inhibitory action and, with the exception of cupric ions, the other substances mentioned above were ineffective as inhibitors. The data presented show that the use of NBT to detect the presence of O2-. is fraught with difficulties due to an equally rapid reduction of NBT by NADH and PMS under anaerobic conditions."}
{"id": "PMID:214252", "title": "[Effect of sodium butyrate on the interferon sensitivity of normal or cells transformed by murine sarcoma virus].", "content": "Sodium butyrate enhances the sensitivity of MSV transformed murine cells to interferon, but does not influence the response of normal cells. Sodium butyrate might act in transformed cells by restoring the different elements of the cytoskeletal system.", "contents": "[Effect of sodium butyrate on the interferon sensitivity of normal or cells transformed by murine sarcoma virus]. Sodium butyrate enhances the sensitivity of MSV transformed murine cells to interferon, but does not influence the response of normal cells. Sodium butyrate might act in transformed cells by restoring the different elements of the cytoskeletal system."}
{"id": "PMID:214253", "title": "[Immunocytochemical localization of neurons containing ACTH 17-39 in the rat brain].", "content": "Immunoreactive neurons and fibers were localized in the Rat brain by immunocytochemistry using an anti-ACTH 17-39 antiserum. Neither adrenalectomy nor water deprivation affected intensity of distribution of reaction of labelled neurons whereas colchicine increased labelling of hypothalamic perikarya. These results support the neuronal origin of cerebral ACTH.", "contents": "[Immunocytochemical localization of neurons containing ACTH 17-39 in the rat brain]. Immunoreactive neurons and fibers were localized in the Rat brain by immunocytochemistry using an anti-ACTH 17-39 antiserum. Neither adrenalectomy nor water deprivation affected intensity of distribution of reaction of labelled neurons whereas colchicine increased labelling of hypothalamic perikarya. These results support the neuronal origin of cerebral ACTH."}
{"id": "PMID:214254", "title": "The immediate pressor response to saralasin in man: a test of angiotensin II receptor vacancy.", "content": "Saralasin, 10 microgram/kg per min, caused an immediate rise in blood pressure in 52 of 57 (91.2%) hypertensive patients. The increase in diastolic pressure averaged 18.8 +/- 1.83 mm Hg (mean +/- SE) in normal renin patients on a normal salt intake. This immediate pressor response was absent in only five high renin patients and, conversely, was very large in three low renin patients. Direct arterial recordings are necessary to define the response accurately; it begins in 60--90 seconds, peaks in amplitude at 2.05 +/- 0.38 minutes, and subsides over the next 5 minutes in normal renin and high renin patients. The blood pressure elevation is inversely related to background plasma renin activity (r = -0.66, P less than 0.001), and also is directly, but weakly, related to 24-hour urinary sodium excretion (r = + 0.29). Therefore, the amplitude of the elevation is predictably diminished by the rise in plasma renin consequent to prior sodium restriction, and also by preliminary receptor exposure to low dose nonpressor infusions of saralasin itself (0.01-0.1 microgram/kg per min). Phentolamine had no effect on the response in two patients. We propose that the immediate pressor response to saralasin is related directly to the preexisting degree of vacancy of angiotensin II vascular receptors and that the initial agonistic action of the drug may prove useful in defining the angiotensin II receptor status in hypertensive diseases.", "contents": "The immediate pressor response to saralasin in man: a test of angiotensin II receptor vacancy. Saralasin, 10 microgram/kg per min, caused an immediate rise in blood pressure in 52 of 57 (91.2%) hypertensive patients. The increase in diastolic pressure averaged 18.8 +/- 1.83 mm Hg (mean +/- SE) in normal renin patients on a normal salt intake. This immediate pressor response was absent in only five high renin patients and, conversely, was very large in three low renin patients. Direct arterial recordings are necessary to define the response accurately; it begins in 60--90 seconds, peaks in amplitude at 2.05 +/- 0.38 minutes, and subsides over the next 5 minutes in normal renin and high renin patients. The blood pressure elevation is inversely related to background plasma renin activity (r = -0.66, P less than 0.001), and also is directly, but weakly, related to 24-hour urinary sodium excretion (r = + 0.29). Therefore, the amplitude of the elevation is predictably diminished by the rise in plasma renin consequent to prior sodium restriction, and also by preliminary receptor exposure to low dose nonpressor infusions of saralasin itself (0.01-0.1 microgram/kg per min). Phentolamine had no effect on the response in two patients. We propose that the immediate pressor response to saralasin is related directly to the preexisting degree of vacancy of angiotensin II vascular receptors and that the initial agonistic action of the drug may prove useful in defining the angiotensin II receptor status in hypertensive diseases."}
{"id": "PMID:214255", "title": "Carotid sinus reflex coronary vasoconstriction during controlled myocardial oxygen metabolism in the dog.", "content": "We studied carotid baroreceptor reflex coronary vasoconstriction in closed-chest dogs with controlled aortic blood pressure and myocardial oxygen metabloism. The dogs were anesthetized with morphine and chloralose. Left coronary blood flow was measured by a cannula-tip flowmeter, and myocardial oxygen metabolism was calculated by measuring the arterial-coronary sinus oxygen difference. A bilateral vagotomy was performed in all animals and they were treated with propranolol. Reduction of carotid sinus pressure to 40 mm Hg caused an increase in aortic pressure that was limited to 15 mm Hg by means of a pressure-control reservoir. During carotid hypotension, heart rate and myocardial oxygen metabolism were unchanged but diastolic conronary vascular resistance increased by 21%. Intracoronary artery infusion of norepinephrine had similar effects. After interruption of the reflex are with the alpha-adrenergic receptor antagonist, dibozane, carotid sinus hypotension and the same increase in aortic pressure (15 mm Hg) resulted in only a 5% increase in diastolic coronary resistance. Dibozane also reduced the coronary responses to norepinephrine. It is concluded that carotid sinus hypotension results in reflex sympathetic alpha-receptor coronary vasoconstriction and that this reflex vasoconstriction is independent of changes in myocardial oxygen metabolism or changes in aortic pressure.", "contents": "Carotid sinus reflex coronary vasoconstriction during controlled myocardial oxygen metabolism in the dog. We studied carotid baroreceptor reflex coronary vasoconstriction in closed-chest dogs with controlled aortic blood pressure and myocardial oxygen metabloism. The dogs were anesthetized with morphine and chloralose. Left coronary blood flow was measured by a cannula-tip flowmeter, and myocardial oxygen metabolism was calculated by measuring the arterial-coronary sinus oxygen difference. A bilateral vagotomy was performed in all animals and they were treated with propranolol. Reduction of carotid sinus pressure to 40 mm Hg caused an increase in aortic pressure that was limited to 15 mm Hg by means of a pressure-control reservoir. During carotid hypotension, heart rate and myocardial oxygen metabolism were unchanged but diastolic conronary vascular resistance increased by 21%. Intracoronary artery infusion of norepinephrine had similar effects. After interruption of the reflex are with the alpha-adrenergic receptor antagonist, dibozane, carotid sinus hypotension and the same increase in aortic pressure (15 mm Hg) resulted in only a 5% increase in diastolic coronary resistance. Dibozane also reduced the coronary responses to norepinephrine. It is concluded that carotid sinus hypotension results in reflex sympathetic alpha-receptor coronary vasoconstriction and that this reflex vasoconstriction is independent of changes in myocardial oxygen metabolism or changes in aortic pressure."}
{"id": "PMID:214256", "title": "Anion-exchange chromatography of erythrocytic and muscle adenylate kinase and its effect on the serum creatine kinase isoenzyme assays.", "content": "We determined the elution profile of erythrocytic and muscle adenylate kinases (EC 2.7.4.3) in the Roche chromatographic creatine kinase procedure and studied the interference these enzymes would cause in the isolation and assay of serum creatine kinase (EC 2.7.3.2) isoenzymes. Both adenylate kinases co-elute with the creatine kinase MM fraction and do not interfere with the isolation or assay of the MB fraction.", "contents": "Anion-exchange chromatography of erythrocytic and muscle adenylate kinase and its effect on the serum creatine kinase isoenzyme assays. We determined the elution profile of erythrocytic and muscle adenylate kinases (EC 2.7.4.3) in the Roche chromatographic creatine kinase procedure and studied the interference these enzymes would cause in the isolation and assay of serum creatine kinase (EC 2.7.3.2) isoenzymes. Both adenylate kinases co-elute with the creatine kinase MM fraction and do not interfere with the isolation or assay of the MB fraction."}
{"id": "PMID:214257", "title": "High-density lipoproteins estimated by an enzymatic cholesterol procedure, with a centrifugal analyzer.", "content": "We describe an assay for high-density lipoprotein cholesterol, adapted to a centrifugal analyzer, the GEMSAEC System 3, which includes use of an increased Mn2+concentration (91 mmol/liter) [J. Lipid Res. 19, 65 (1978)] and ethylenediaminetetraacetate [Clin. Chem. 22, 98 (1976)]. Modifications to the GEMSAEC system include reducing the mixing burst and preconditioning the sample tip. Accuracy of this procedure, as assessed by analysis of a control pool from the Center for Disease Control, was 99.2%. Day-to-day precision for two control pools was 320 +/- 13 and 506 +/- 17 mg/liter. Serum sample volume was decreased to 0.5 ml. In blanks with heparin/Mn2+ present, the pseudocholesterol concentrations resulting from a reaction of the enzymatic cholesterol reagent and the heparin/Mn2+ precipitating reagent depend on the source of the enzymatic reagent and appear to be enhanced slightly by the use of ethylenediaminetetraacetate. Pseudocholesterol concentrations reach a maximum at heparin/Mn2+ concentrations well below those needed to completely precipitate the low-density and very-low-density lipoprotein fractions. Population reference values were obtained from analyses done on 224 local physicians (mean: male, 500 mg/liter; female, 620 mg/liter) and 156 ambulatory patients (mean: male, 463 mg/liter; female, 553 mg/liter).", "contents": "High-density lipoproteins estimated by an enzymatic cholesterol procedure, with a centrifugal analyzer. We describe an assay for high-density lipoprotein cholesterol, adapted to a centrifugal analyzer, the GEMSAEC System 3, which includes use of an increased Mn2+concentration (91 mmol/liter) [J. Lipid Res. 19, 65 (1978)] and ethylenediaminetetraacetate [Clin. Chem. 22, 98 (1976)]. Modifications to the GEMSAEC system include reducing the mixing burst and preconditioning the sample tip. Accuracy of this procedure, as assessed by analysis of a control pool from the Center for Disease Control, was 99.2%. Day-to-day precision for two control pools was 320 +/- 13 and 506 +/- 17 mg/liter. Serum sample volume was decreased to 0.5 ml. In blanks with heparin/Mn2+ present, the pseudocholesterol concentrations resulting from a reaction of the enzymatic cholesterol reagent and the heparin/Mn2+ precipitating reagent depend on the source of the enzymatic reagent and appear to be enhanced slightly by the use of ethylenediaminetetraacetate. Pseudocholesterol concentrations reach a maximum at heparin/Mn2+ concentrations well below those needed to completely precipitate the low-density and very-low-density lipoprotein fractions. Population reference values were obtained from analyses done on 224 local physicians (mean: male, 500 mg/liter; female, 620 mg/liter) and 156 ambulatory patients (mean: male, 463 mg/liter; female, 553 mg/liter)."}
{"id": "PMID:214258", "title": "The hypercalciuria of diabetes mellitus: its amelioration with insulin.", "content": "Calcium and phosphous metabolism was investigated in 20 patients with diabetes mellitus when their diabetes was under poor metabolic control and again once optimal glycaemic control was achieved with aggressive insulin therapy. Ten of the twenty uncontrolled diabetics had hypercalciuria; insulin therapy returned calcium excretion to normal in five. Twenty-four hour calcium excretion fell in all but two patients when optimal diabetic control was achieved and calcium excretion was positively correlated with glucose excretion. Urinary cyclic AMP excretion, which was in the high normal range during poor control, decreased significantly during optimal insulin therapy. These data suggest that the hypercalciuria of uncontrolled diabetes may be a form of renal hypercalciuria which could result in parathyroid stimulation which might contribute to the development of osteopenia in patients with diabetes mellitus.", "contents": "The hypercalciuria of diabetes mellitus: its amelioration with insulin. Calcium and phosphous metabolism was investigated in 20 patients with diabetes mellitus when their diabetes was under poor metabolic control and again once optimal glycaemic control was achieved with aggressive insulin therapy. Ten of the twenty uncontrolled diabetics had hypercalciuria; insulin therapy returned calcium excretion to normal in five. Twenty-four hour calcium excretion fell in all but two patients when optimal diabetic control was achieved and calcium excretion was positively correlated with glucose excretion. Urinary cyclic AMP excretion, which was in the high normal range during poor control, decreased significantly during optimal insulin therapy. These data suggest that the hypercalciuria of uncontrolled diabetes may be a form of renal hypercalciuria which could result in parathyroid stimulation which might contribute to the development of osteopenia in patients with diabetes mellitus."}
{"id": "PMID:214259", "title": "Antidiuretic hormone in bronchogenic carcinoma.", "content": "Immunoactive antidiuretic hormone (ADH) was measured by radioimmunoassay in the plasma, lung tumours and metastatic tumours of nineteen patients with bronchogenic carcinoma. Ten patients had hyponatraemia and carcinoma of the small oat cell type. Plasma ADH measured in nine of these patients ranged from 11--270 pg/ml and was elevated above the normal range (4.6--6.2 pg/ml) in all subjects. ADH-immunoreactive material was detectable in all primary lung tumours (range 9--1080 pg/mg wet weight, n = 7) and metastases (range 5--63 pg/mg wet weight, n = 9) obtained from the hyponatraemic patients. A statistical relationship existed between plasma and tumour ADH concentration in six patients where both measurements were performed. Three patients had small cell carcinomas (two oat cell and one anaplastic) without overt hyponatraemia. ADH-like material was detectable in the lung tumours (18 and 1.1 pg/mg wet weight) and liver metastases (4 and 1.0 pg/mg wet weight) of two patients but not in the third. Four of the remaining patients had squamous cell carcinomas and two had adenocarcinomas. None had hyponatraemia. ADH-like material was undetectable in all lung tumours, metastatic tumours and uninvolved tissue from these patients. ADH extracted from the pituitaries of four patients ranged from 6400--13200 pg/mg wet weight. ADH immunoreactive extracts of six lung tumours and nine metastases (all oat cell) showed the same pattern on elution from a Sephadex G-25 column. A large peak, which made up 65% of the total activity, was eluted in the same position as synthetic arginine vasopressin and contained comparable amounts of immunoreactive and bioactive ADH. Two smaller peaks (8 and 27% of total activity) were eluted in positions of higher molecular weight and contained more immunoreactive than bioactive ADH. In contrast, three of four pituitary extracts showed only a single peak which eluted in the same position as marker vasopressin.", "contents": "Antidiuretic hormone in bronchogenic carcinoma. Immunoactive antidiuretic hormone (ADH) was measured by radioimmunoassay in the plasma, lung tumours and metastatic tumours of nineteen patients with bronchogenic carcinoma. Ten patients had hyponatraemia and carcinoma of the small oat cell type. Plasma ADH measured in nine of these patients ranged from 11--270 pg/ml and was elevated above the normal range (4.6--6.2 pg/ml) in all subjects. ADH-immunoreactive material was detectable in all primary lung tumours (range 9--1080 pg/mg wet weight, n = 7) and metastases (range 5--63 pg/mg wet weight, n = 9) obtained from the hyponatraemic patients. A statistical relationship existed between plasma and tumour ADH concentration in six patients where both measurements were performed. Three patients had small cell carcinomas (two oat cell and one anaplastic) without overt hyponatraemia. ADH-like material was detectable in the lung tumours (18 and 1.1 pg/mg wet weight) and liver metastases (4 and 1.0 pg/mg wet weight) of two patients but not in the third. Four of the remaining patients had squamous cell carcinomas and two had adenocarcinomas. None had hyponatraemia. ADH-like material was undetectable in all lung tumours, metastatic tumours and uninvolved tissue from these patients. ADH extracted from the pituitaries of four patients ranged from 6400--13200 pg/mg wet weight. ADH immunoreactive extracts of six lung tumours and nine metastases (all oat cell) showed the same pattern on elution from a Sephadex G-25 column. A large peak, which made up 65% of the total activity, was eluted in the same position as synthetic arginine vasopressin and contained comparable amounts of immunoreactive and bioactive ADH. Two smaller peaks (8 and 27% of total activity) were eluted in positions of higher molecular weight and contained more immunoreactive than bioactive ADH. In contrast, three of four pituitary extracts showed only a single peak which eluted in the same position as marker vasopressin."}
{"id": "PMID:214260", "title": "Discrepancy between ACTH and cortisol responses to insulin induced hypoglycaemia.", "content": "The purpose of this study was to assess the normal relationship between plasma ACTH and cortisol during insulin induced hypoglycaemia. Twenty-six healthy persons were studied. Peak plasma concentration and the amounts of ACTH and cortisol secreted during hypoglycaemia were compared. There was no significant correlation between the ACTH and cortisol values. The ACTH responses varied significantly more than those of cortisol. This probably signifies an over-capacity of ACTH secretion in comparison to the secretory capacity of the adrenal cortex.", "contents": "Discrepancy between ACTH and cortisol responses to insulin induced hypoglycaemia. The purpose of this study was to assess the normal relationship between plasma ACTH and cortisol during insulin induced hypoglycaemia. Twenty-six healthy persons were studied. Peak plasma concentration and the amounts of ACTH and cortisol secreted during hypoglycaemia were compared. There was no significant correlation between the ACTH and cortisol values. The ACTH responses varied significantly more than those of cortisol. This probably signifies an over-capacity of ACTH secretion in comparison to the secretory capacity of the adrenal cortex."}
{"id": "PMID:214265", "title": "Liver metastases of oat cell carcinoma of lung detected on 99mTc-diphosphonate bone scan.", "content": "Colon carcinoma, cholangiocarcinoma, malignant melanoma and liver metastases detected on bone imaging have been reported with different bone seeking radiopharmaceuticals. This report is concerned with an interesting case of oat cell carcinoma with hepatic metatases visualized on 99mTc-diphosphonate bone imaging. This has not been previously reported.", "contents": "Liver metastases of oat cell carcinoma of lung detected on 99mTc-diphosphonate bone scan. Colon carcinoma, cholangiocarcinoma, malignant melanoma and liver metastases detected on bone imaging have been reported with different bone seeking radiopharmaceuticals. This report is concerned with an interesting case of oat cell carcinoma with hepatic metatases visualized on 99mTc-diphosphonate bone imaging. This has not been previously reported."}
{"id": "PMID:214268", "title": "Haemodynamics of orally-active converting enzyme inhibitor (SQ 14225) in hypertensive patients.", "content": "1. The haemodynamic effects of oral converting enzyme inhibitor (SQ 14225) were assessed in eight patients with severe essential or renovascular hypertension. 2. Mean arterial pressure fell (149 +/- 5 to 127 +/- 8 mmHg, P less than 0.02), because of a fall in total peripheral resistance (6.9 +/- 0.53 to 5.7 +/- 0.40 kPa 1(-1)s m2) without a significant change in cardiac index. Two of the eight patients were non-responders without pressure reduction or a haemodynamic change. Sodium restriction (10 mmol/day) while the same dose of SQ 14225 was continued further lowered arterial pressure (137 +/- 8 to 111 +/- 12 mmHg, P less than 0.05) through further resistance reduction (6.5 +/- 0.53 to 5.2 +/- 0.40 kPa 1(-1)s m2, P less than 0.05). 3. Haemodynamic responses to head-up tilt (increased heart rate and resistance, decreased cardiac index) were unaffected by SQ 14225 regardless of sodium intake. 4. The pattern of reduction in peripheral resistance, with unchanged cardiac index, was similar to that produced by vasodilators acting at both arteriolar and venular levels.", "contents": "Haemodynamics of orally-active converting enzyme inhibitor (SQ 14225) in hypertensive patients. 1. The haemodynamic effects of oral converting enzyme inhibitor (SQ 14225) were assessed in eight patients with severe essential or renovascular hypertension. 2. Mean arterial pressure fell (149 +/- 5 to 127 +/- 8 mmHg, P less than 0.02), because of a fall in total peripheral resistance (6.9 +/- 0.53 to 5.7 +/- 0.40 kPa 1(-1)s m2) without a significant change in cardiac index. Two of the eight patients were non-responders without pressure reduction or a haemodynamic change. Sodium restriction (10 mmol/day) while the same dose of SQ 14225 was continued further lowered arterial pressure (137 +/- 8 to 111 +/- 12 mmHg, P less than 0.05) through further resistance reduction (6.5 +/- 0.53 to 5.2 +/- 0.40 kPa 1(-1)s m2, P less than 0.05). 3. Haemodynamic responses to head-up tilt (increased heart rate and resistance, decreased cardiac index) were unaffected by SQ 14225 regardless of sodium intake. 4. The pattern of reduction in peripheral resistance, with unchanged cardiac index, was similar to that produced by vasodilators acting at both arteriolar and venular levels."}
{"id": "PMID:214264", "title": "Blood pressure and metabolic effects of ACTH in anephric sheep.", "content": "1. ACTH (80--100 iu/day) was administered to seven sheep for 3--5 days following bilateral nephrectomy. 2. ACTH treatment produced rises in mean arterial pressure in anephric sheep similar to those observed in intact animals. Following withdrawal of ACTH, blood pressure declined over the following 72 h. 3. ACTH produced a transient fall in plasma potassium and anephric sheep, suggesting an internal redistribution mechanism for this ion. 4. These studies demonstrate that adrenal steroid hormones can modify blood pressure in the absence of the kidney.", "contents": "Blood pressure and metabolic effects of ACTH in anephric sheep. 1. ACTH (80--100 iu/day) was administered to seven sheep for 3--5 days following bilateral nephrectomy. 2. ACTH treatment produced rises in mean arterial pressure in anephric sheep similar to those observed in intact animals. Following withdrawal of ACTH, blood pressure declined over the following 72 h. 3. ACTH produced a transient fall in plasma potassium and anephric sheep, suggesting an internal redistribution mechanism for this ion. 4. These studies demonstrate that adrenal steroid hormones can modify blood pressure in the absence of the kidney."}
{"id": "PMID:214271", "title": "Translation of procollagen messenger RNA in a cell free system derived from wheat germ: hydroxylation of prolyl residues in the product.", "content": "Ribonucleic acid extracted from chick embryo calvaria directs the synthesis of a collagenous product in a cell-free system. A portion of the prolyl residues incorporated into this protein can be hydroxylated in vitro by prolyl hydroxylase as demonstrated by the release of 3H-H20 from 3H-proline and by the direct demonstration of 3H-hydroxyproline in acid hydrolysates of the product. Thirty percent of potential sites become hydroxylated in the in vitro reaction using either cell-free product or an underhydroxylated collagen extracted from chick calvaria. Neither prolonged incubation nor increased levels of enzyme increased the extent of hydroxylation in either substrate.", "contents": "Translation of procollagen messenger RNA in a cell free system derived from wheat germ: hydroxylation of prolyl residues in the product. Ribonucleic acid extracted from chick embryo calvaria directs the synthesis of a collagenous product in a cell-free system. A portion of the prolyl residues incorporated into this protein can be hydroxylated in vitro by prolyl hydroxylase as demonstrated by the release of 3H-H20 from 3H-proline and by the direct demonstration of 3H-hydroxyproline in acid hydrolysates of the product. Thirty percent of potential sites become hydroxylated in the in vitro reaction using either cell-free product or an underhydroxylated collagen extracted from chick calvaria. Neither prolonged incubation nor increased levels of enzyme increased the extent of hydroxylation in either substrate."}
{"id": "PMID:214266", "title": "Research review. Interactions between environmental chemicals and drug biotransformation in man.", "content": "Many factors influence the metabolism of drugs in man. Besides genetic factors, environmental factors may play a significant role in explaining the variation observed in the rates of drug metabolism between different individuals. Intentional or unintentional exposure to environmental chemicals could enhance or inhibit the activity of hepatic mixed function oxidases that metabolise drugs and other foreign chemicals, as well as endogenous substrates such as steroid hormones. A major source of such exposure may be occupational. Exposure to the heavy metal, lead, has been shown to inhibit drug metabolism; whereas intensive exposure to chlorinated insecticides, and other halogenated hydrocarbons such as polychlorinated biphenyls, has been shown to enhance the metabolism of test drugs such as antipyrine and phenylbutazone. An intentional source of exposure to foreign chemicals is cigarette smoke. Cigarette smoke contains polycyclic hydrocarbons, which are known inducers of hepatic mixed function oxidases. A number of studies have shown that cigarette smoking can alter the pharmacological action and/or the metabolism of some drugs. Pharmacokinetic studies have shown that cigarette smoking decreases the bioavailability of phenacetin and increases dosage requirements of theophylline by enhancing their rate of metabolism. Data, which are not very conclusive, indicate that heavy marijuana use may have an inhibitory effect on metabolism of some drugs and an inducing effect on others such as theophylline. Dietary factors may also play a significant role in the regulation of drug metabolism. Charcoal broiling which introduces polycyclic hydrocarbons into foods has been shown to enhance the metabolism of the test drug, antipyrine, and of such commonly used drugs as phenacetin and theophylline. Such intentional or unintentional exposure to environmental chemicals which may alter the rates of drug metabolism in man indicates the importance of individualisation of drug therapy.", "contents": "Research review. Interactions between environmental chemicals and drug biotransformation in man. Many factors influence the metabolism of drugs in man. Besides genetic factors, environmental factors may play a significant role in explaining the variation observed in the rates of drug metabolism between different individuals. Intentional or unintentional exposure to environmental chemicals could enhance or inhibit the activity of hepatic mixed function oxidases that metabolise drugs and other foreign chemicals, as well as endogenous substrates such as steroid hormones. A major source of such exposure may be occupational. Exposure to the heavy metal, lead, has been shown to inhibit drug metabolism; whereas intensive exposure to chlorinated insecticides, and other halogenated hydrocarbons such as polychlorinated biphenyls, has been shown to enhance the metabolism of test drugs such as antipyrine and phenylbutazone. An intentional source of exposure to foreign chemicals is cigarette smoke. Cigarette smoke contains polycyclic hydrocarbons, which are known inducers of hepatic mixed function oxidases. A number of studies have shown that cigarette smoking can alter the pharmacological action and/or the metabolism of some drugs. Pharmacokinetic studies have shown that cigarette smoking decreases the bioavailability of phenacetin and increases dosage requirements of theophylline by enhancing their rate of metabolism. Data, which are not very conclusive, indicate that heavy marijuana use may have an inhibitory effect on metabolism of some drugs and an inducing effect on others such as theophylline. Dietary factors may also play a significant role in the regulation of drug metabolism. Charcoal broiling which introduces polycyclic hydrocarbons into foods has been shown to enhance the metabolism of the test drug, antipyrine, and of such commonly used drugs as phenacetin and theophylline. Such intentional or unintentional exposure to environmental chemicals which may alter the rates of drug metabolism in man indicates the importance of individualisation of drug therapy."}
{"id": "PMID:214276", "title": "Skeletal maturation of children living in areas with a different contamination of the atmosphere.", "content": "Based on the evaluation of more than 5000 X-rays pictures of the left hand and wrist of children living in areas with a different degree of atmospheric contamination in the CSSR, GDR and GFR evidence was provided that children living in areas with a high concentration of industrial exhalations are, as compared with reletively clean areas, significantly retarded in their skeletal maturation. This retardation was in the great majority greater in boys than girls which indicates a different reactivity of the two sexes to noxious agents of the external environment.", "contents": "Skeletal maturation of children living in areas with a different contamination of the atmosphere. Based on the evaluation of more than 5000 X-rays pictures of the left hand and wrist of children living in areas with a different degree of atmospheric contamination in the CSSR, GDR and GFR evidence was provided that children living in areas with a high concentration of industrial exhalations are, as compared with reletively clean areas, significantly retarded in their skeletal maturation. This retardation was in the great majority greater in boys than girls which indicates a different reactivity of the two sexes to noxious agents of the external environment."}
{"id": "PMID:214288", "title": "Responsiveness to stimulation during paradoxical sleep in infants.", "content": "11 healthy children were repeatedly studied during 2 sleep cycles in 2 sessions at 2,6, 12 and 20 wk of life. Three acoustic stimuli, light and tactile stimulus were applied in a randomized order in intervals ranging randomly from 30 to 120 sec. Continuous polygraphic recordings were made of respiration, REMs, EEG and EMG of biceps and triceps brachii. The effect of stimuli on the length of paradoxical sleep, REMs and EMG was assessed. There were age-related changes in the number of REMs after stimuli. At 2 and 6 wk no stimulus elicited any change. At 12 wk the children responded with an increased number of rapid eye movements to acoustic stimuli, at 20 wk they responded to acoustic stimuli and light. The conclusion is that, as far as REMs are concerned, responsiveness during paradoxical sleep changes with age. There was a difference in the incidence of EOG responses and EMG responses. These findings show that it is not possible to assess responsiveness in infants during PS by one measure only.", "contents": "Responsiveness to stimulation during paradoxical sleep in infants. 11 healthy children were repeatedly studied during 2 sleep cycles in 2 sessions at 2,6, 12 and 20 wk of life. Three acoustic stimuli, light and tactile stimulus were applied in a randomized order in intervals ranging randomly from 30 to 120 sec. Continuous polygraphic recordings were made of respiration, REMs, EEG and EMG of biceps and triceps brachii. The effect of stimuli on the length of paradoxical sleep, REMs and EMG was assessed. There were age-related changes in the number of REMs after stimuli. At 2 and 6 wk no stimulus elicited any change. At 12 wk the children responded with an increased number of rapid eye movements to acoustic stimuli, at 20 wk they responded to acoustic stimuli and light. The conclusion is that, as far as REMs are concerned, responsiveness during paradoxical sleep changes with age. There was a difference in the incidence of EOG responses and EMG responses. These findings show that it is not possible to assess responsiveness in infants during PS by one measure only."}
{"id": "PMID:214289", "title": "Thoracico-abdominal respiratory correlations in infants: constancy and variability in different sleep states.", "content": "28 polygraphic recordings were made in normal infants: 20 in full-term newborns and 8 in 2- to 10-wk-old babies. Data were analysed by 20-sec epochs. Relationships between thoracic (3rd-4th rib level) and abdominal respiratory movements were studied according to their maximum out-of-phase occurring (180 degrees maximum) in every 20-sec period. The thoracico-abdominal phase relationships according to sleep states do not change during the first trimester of life. In quiet sleep, while in-pase thoracico-abdominal respiration was the most frequent pattern, the out-of-phase one was also a possible pattern. In active sleep, out-of-phase respiration is characteristic, in-phase relation being a rare exception. In transitional sleep, respiratory relationships could be those appropriate for the preceding or the following sleep state. Nasal air flow always occurred in the phase with abdominal movements. Total flatteninf of thoracicorespiratory movements only were found in all sleep states; these thoracic flattenings must be differentiated from apnea. Transient fluctuations in the degree of phase relations are possible. There exists both interand intraindividual variability in normal infants. Variability of fusimotor system tonus is probably the neurological mechanism underling these phenomena.", "contents": "Thoracico-abdominal respiratory correlations in infants: constancy and variability in different sleep states. 28 polygraphic recordings were made in normal infants: 20 in full-term newborns and 8 in 2- to 10-wk-old babies. Data were analysed by 20-sec epochs. Relationships between thoracic (3rd-4th rib level) and abdominal respiratory movements were studied according to their maximum out-of-phase occurring (180 degrees maximum) in every 20-sec period. The thoracico-abdominal phase relationships according to sleep states do not change during the first trimester of life. In quiet sleep, while in-pase thoracico-abdominal respiration was the most frequent pattern, the out-of-phase one was also a possible pattern. In active sleep, out-of-phase respiration is characteristic, in-phase relation being a rare exception. In transitional sleep, respiratory relationships could be those appropriate for the preceding or the following sleep state. Nasal air flow always occurred in the phase with abdominal movements. Total flatteninf of thoracicorespiratory movements only were found in all sleep states; these thoracic flattenings must be differentiated from apnea. Transient fluctuations in the degree of phase relations are possible. There exists both interand intraindividual variability in normal infants. Variability of fusimotor system tonus is probably the neurological mechanism underling these phenomena."}
{"id": "PMID:214290", "title": "Respiratory and motor events in sleeping infants: their correlation with thoracico-abdominal respiratory relationships.", "content": "28 polygraphic recordings were made in normal infants: 20 in full-term newborns and 8 in 2- to 10-wk-old babies. In full-term newborns sighs and apneas (greater than 5 sec) were significantly more numerous in active (REM) sleep, while startles prevailed in quiet (NREM) sleep. The incidence of all these events diminished with age. Important interindividual differences of their frequency were noted in normal babies. There were not time correlations between the apneas (decreasing from newborns to 2-10 wk of age) and out-of-phase respiration in active sleep (no changing during the same period). Sighs, apneas, startles and limb movements did not modify phase relationships between thoracic and abdominal movements. Where movements were out of phase, only body movements involving the thorax were followed by transient period with in phase respiratory movements. Coincidences between occurrence of sighs, apneas, startles, gross body movements and respiratory amplitude diminution were calculated. There was no constant parallelism between out-of-phase thoracico-abdominal respiration and tonic chin activity inhibition nor respiratory rate irregularity. A hypothesis on neurological mechanism underlining these phenomena is proposed.", "contents": "Respiratory and motor events in sleeping infants: their correlation with thoracico-abdominal respiratory relationships. 28 polygraphic recordings were made in normal infants: 20 in full-term newborns and 8 in 2- to 10-wk-old babies. In full-term newborns sighs and apneas (greater than 5 sec) were significantly more numerous in active (REM) sleep, while startles prevailed in quiet (NREM) sleep. The incidence of all these events diminished with age. Important interindividual differences of their frequency were noted in normal babies. There were not time correlations between the apneas (decreasing from newborns to 2-10 wk of age) and out-of-phase respiration in active sleep (no changing during the same period). Sighs, apneas, startles and limb movements did not modify phase relationships between thoracic and abdominal movements. Where movements were out of phase, only body movements involving the thorax were followed by transient period with in phase respiratory movements. Coincidences between occurrence of sighs, apneas, startles, gross body movements and respiratory amplitude diminution were calculated. There was no constant parallelism between out-of-phase thoracico-abdominal respiration and tonic chin activity inhibition nor respiratory rate irregularity. A hypothesis on neurological mechanism underlining these phenomena is proposed."}
{"id": "PMID:214293", "title": "Inhibition of thyroidal cyclic AMP-dependent protein kinase by thyroid hormone.", "content": "Bovine thyroid cyclic AMP-dependent protein kinase was purified by DEAE-Sephadex and Sephadex G-200 chromatography. This preparation showed a 240-fold increase in specific activity over the initial 20,000 x g supernatant with histone as substrate and 1 micronM cyclic AMP in the assay mixture. In the presence of 2.5 X 10(-5)M L-triiodothyronine (T3), protein kinase activity was significantly reduced; 50% inhibition was achieved at 1 X 10(-4) M. Tests of diverse thyroid hormone analogs showed that T3 and its derivatives were more potent inhibitors than T4 and its derivatives which, in turn, were more potent than thyronine or diiodothyronine. Mono- and diiodotyrosine, tyrosine, and iodide were without effect. Triiodothyronine did not inhibit kidney, spleen, or lung protein kinase activity. The magnitude of the inhibition was the same whether or not cyclic AMP (1 micronM) was present in the incubation mixture, suggesting an effect on the catalytic, rather than the regulatory subunit of the enzyme. The inhibition of protein kinase by thyroid hormone was not influenced by Mg++ concentration but was overcome in a competitive manner by increasing ATP concentration. Increasing the histone concentration did not modify the inhibition. Although these studies suggest a novel cellular control mechanism, the high thyroid hormone concentrations required and the lack of concordance between inhibitory effects and biologic activity of the analogs tested precludes assumption of physiologic relevance.", "contents": "Inhibition of thyroidal cyclic AMP-dependent protein kinase by thyroid hormone. Bovine thyroid cyclic AMP-dependent protein kinase was purified by DEAE-Sephadex and Sephadex G-200 chromatography. This preparation showed a 240-fold increase in specific activity over the initial 20,000 x g supernatant with histone as substrate and 1 micronM cyclic AMP in the assay mixture. In the presence of 2.5 X 10(-5)M L-triiodothyronine (T3), protein kinase activity was significantly reduced; 50% inhibition was achieved at 1 X 10(-4) M. Tests of diverse thyroid hormone analogs showed that T3 and its derivatives were more potent inhibitors than T4 and its derivatives which, in turn, were more potent than thyronine or diiodothyronine. Mono- and diiodotyrosine, tyrosine, and iodide were without effect. Triiodothyronine did not inhibit kidney, spleen, or lung protein kinase activity. The magnitude of the inhibition was the same whether or not cyclic AMP (1 micronM) was present in the incubation mixture, suggesting an effect on the catalytic, rather than the regulatory subunit of the enzyme. The inhibition of protein kinase by thyroid hormone was not influenced by Mg++ concentration but was overcome in a competitive manner by increasing ATP concentration. Increasing the histone concentration did not modify the inhibition. Although these studies suggest a novel cellular control mechanism, the high thyroid hormone concentrations required and the lack of concordance between inhibitory effects and biologic activity of the analogs tested precludes assumption of physiologic relevance."}
{"id": "PMID:214294", "title": "An examination of possible mechanisms of angiotensin II-stimulated steroidogenesis.", "content": "Dog and rat adrenal glomerulosa cells and subcellular fractions have been utilized to evaluate the mechanism of angiotensin II- and angiotensin III-induced aldosterone production. The effects of angiotensin, ACTH, and potassium have been compared on cyclic AMP and cyclic GMP in isolated glomerulosa cells and adenylate cyclase activity in subcellular fractions. The effect of angiotensin II has also been assessed on Na+-K+-activated ATPase of plasma membrane enriched fractions of dog and rat adrenals. We have demonstrated no effect of angiotensin II or angiotensin III on either adenylate cyclase, cyclic AMP, cyclic GMP, or Na+-K+-dependent ATPase activity over a wide range of concentrations. Potassium ion in concentrations that stimulate significant aldosterone production was also without effect. The negative effects of angiotensin and potassium were contrasted against a positive correlation between an ACTH-induced effect on aldosterone production, adenylate cyclase, and cyclic AMP accumulation. These studies have served to demonstrate that neither adenylate cyclase, cyclic AMP, cyclic GMP, or Na+-K+-activated ATPase seem to be directly involved in the mechanism of action of angiotensins on aldosterone production in the rat and dog adrenal glomerulosa.", "contents": "An examination of possible mechanisms of angiotensin II-stimulated steroidogenesis. Dog and rat adrenal glomerulosa cells and subcellular fractions have been utilized to evaluate the mechanism of angiotensin II- and angiotensin III-induced aldosterone production. The effects of angiotensin, ACTH, and potassium have been compared on cyclic AMP and cyclic GMP in isolated glomerulosa cells and adenylate cyclase activity in subcellular fractions. The effect of angiotensin II has also been assessed on Na+-K+-activated ATPase of plasma membrane enriched fractions of dog and rat adrenals. We have demonstrated no effect of angiotensin II or angiotensin III on either adenylate cyclase, cyclic AMP, cyclic GMP, or Na+-K+-dependent ATPase activity over a wide range of concentrations. Potassium ion in concentrations that stimulate significant aldosterone production was also without effect. The negative effects of angiotensin and potassium were contrasted against a positive correlation between an ACTH-induced effect on aldosterone production, adenylate cyclase, and cyclic AMP accumulation. These studies have served to demonstrate that neither adenylate cyclase, cyclic AMP, cyclic GMP, or Na+-K+-activated ATPase seem to be directly involved in the mechanism of action of angiotensins on aldosterone production in the rat and dog adrenal glomerulosa."}
{"id": "PMID:214298", "title": "Effect of copper and zinc status on susceptibility to cadmium intoxication.", "content": "The effects of dietary cadmium on copper and zinc metabolism in animals are described. Emphasis is given to situations involving chronic exposure to low levels of cadmium, to the identification of population groups most at risk, and to the protective effect of dietary supplementation with copper and zinc. The mechanism of the interaction between the metals and the involvement of metallothionein are discussed.", "contents": "Effect of copper and zinc status on susceptibility to cadmium intoxication. The effects of dietary cadmium on copper and zinc metabolism in animals are described. Emphasis is given to situations involving chronic exposure to low levels of cadmium, to the identification of population groups most at risk, and to the protective effect of dietary supplementation with copper and zinc. The mechanism of the interaction between the metals and the involvement of metallothionein are discussed."}
{"id": "PMID:214299", "title": "Cultured heart cell reaggregate model for studying cardiac toxicology.", "content": "This review represents a summary of the technique of using cultured heart cells as a model system for studying the physiology, pharmacology, biochemistry and toxicology of myocardial cells. The general techniques and types of culture preparations commonly used are given and some of the advantages and disadvantages of working with cultured heart cells are summarized.", "contents": "Cultured heart cell reaggregate model for studying cardiac toxicology. This review represents a summary of the technique of using cultured heart cells as a model system for studying the physiology, pharmacology, biochemistry and toxicology of myocardial cells. The general techniques and types of culture preparations commonly used are given and some of the advantages and disadvantages of working with cultured heart cells are summarized."}
{"id": "PMID:214300", "title": "Physiological response to aerosol propellants.", "content": "Acute exposures to isobutane, propane, F-12, and F-11 in concentrations of 250, 500, or 1000 ppm for periods of 1 min to 8 hr did not produce any untoward physiological effects as determined by the methods employed which included serial EKG's and continuous monitoring of modified V5 by telemetry during exposure. Repetitive exposures to these four propellants were also without measurable untoward physiological effect with the exception of the eight male subjects repetitively exposed to 1000 ppm, F-11, who did show minor decrements in several of the cognitive tests. Of particular importance is the observation that none of the subjects showed any decrement in pulmonary function or alteration in cardiac rhythm as the result of exposure to concentrations of the gases or vapors far greater than encountered in the normal use of aerosol products in the home.", "contents": "Physiological response to aerosol propellants. Acute exposures to isobutane, propane, F-12, and F-11 in concentrations of 250, 500, or 1000 ppm for periods of 1 min to 8 hr did not produce any untoward physiological effects as determined by the methods employed which included serial EKG's and continuous monitoring of modified V5 by telemetry during exposure. Repetitive exposures to these four propellants were also without measurable untoward physiological effect with the exception of the eight male subjects repetitively exposed to 1000 ppm, F-11, who did show minor decrements in several of the cognitive tests. Of particular importance is the observation that none of the subjects showed any decrement in pulmonary function or alteration in cardiac rhythm as the result of exposure to concentrations of the gases or vapors far greater than encountered in the normal use of aerosol products in the home."}
{"id": "PMID:214301", "title": "Proteins bound to heterogeneous nuclear RNA of simian-virus-40-infected cells.", "content": "Heterogeneous nuclear RNA . protein (hnRNA . protein) complexes from simian-virus-40 (SV40)-infected cells late in infection contain 7--10% RNA sequences specific to SV40 DNA. The SV40 nuclear RNA . protein complexes sediment at 60--70 S. The reality and specificity of the RNA-protein association is shown in metrizamide gradients. Protein and RNA lebels of hnRNA . protein-particles in SV40-infected cells follow a parallel pattern with a peak at 1.28 g/cm2 whereas a mixture of ribosomal RNA and soluble cytoplasmic proteins is separated according to the different densities in metrizamide. Analysis of hnRNA . protein from infected cells by two-dimensional gel electrophoresis shows the presence of a number of new proteins. It is demonstrated that three of these proteins are cellular ones induced by the virus infection and hence constitute good candidates to be specific RNA . protein particles for virus nuclear RNA. The presence of actin in hnRNA . protein particles from normal and SV40-infected cells and the presence of the major capsid protein VP1 in hnRNA . protein particles from SV40-infected cells is discussed.", "contents": "Proteins bound to heterogeneous nuclear RNA of simian-virus-40-infected cells. Heterogeneous nuclear RNA . protein (hnRNA . protein) complexes from simian-virus-40 (SV40)-infected cells late in infection contain 7--10% RNA sequences specific to SV40 DNA. The SV40 nuclear RNA . protein complexes sediment at 60--70 S. The reality and specificity of the RNA-protein association is shown in metrizamide gradients. Protein and RNA lebels of hnRNA . protein-particles in SV40-infected cells follow a parallel pattern with a peak at 1.28 g/cm2 whereas a mixture of ribosomal RNA and soluble cytoplasmic proteins is separated according to the different densities in metrizamide. Analysis of hnRNA . protein from infected cells by two-dimensional gel electrophoresis shows the presence of a number of new proteins. It is demonstrated that three of these proteins are cellular ones induced by the virus infection and hence constitute good candidates to be specific RNA . protein particles for virus nuclear RNA. The presence of actin in hnRNA . protein particles from normal and SV40-infected cells and the presence of the major capsid protein VP1 in hnRNA . protein particles from SV40-infected cells is discussed."}
{"id": "PMID:214302", "title": "Immunoprecipitation of a cytoplasmic precursor of rat-liver cytochrome oxidase.", "content": "A simple method for the isolation of rat liver cells is described. The cells are shown, by an isotope dilution method, to maintain a constant rate of protein synthesis for 8 h of incubation. Antibodies to purified rat liver cytochrome oxidase were raised in rabbits and used to investigate the labeling of cytochrome oxidase in isolated rat liver cells and in vivo. The data demonstrate the occurrence of a precursor of the subunits of cytochrome oxidase that are synthesized in the cytoplasm. 1. Dodecylsulfate gel electrophoresis of the immunoprecipitates from isolated rat liver cells that had been labeled with [35S]methionine for 1 h showed a single radioactive peak with a molecular  weight of 50000. 2. Judged by the effects of cycloheximide and chloramphenicol the labeled protein is synthesized on cytoplasmic ribosomes. 3. After labeling for 1 h in vivo with [3H]leucine the labeled protein appears to be exclusively associated with the hepatic microsomal fraction. 4. Ouchterlony double-diffusion analysis demonstrated immunological relationship between the precipitates from microsomes and cytochrome oxidase. In addition to the precipitates derived from mitochondria and microsomes immunoprecipitates were also obtained from the cytosol in comparable amounts; these again were immunologically related. The occurrence of large amounts of precursor(s) (or degradation products) of cytochrome oxidase in rat liver fractions is interpreted in terms of a regulatory pool for amino acid homeostasis in the organism.", "contents": "Immunoprecipitation of a cytoplasmic precursor of rat-liver cytochrome oxidase. A simple method for the isolation of rat liver cells is described. The cells are shown, by an isotope dilution method, to maintain a constant rate of protein synthesis for 8 h of incubation. Antibodies to purified rat liver cytochrome oxidase were raised in rabbits and used to investigate the labeling of cytochrome oxidase in isolated rat liver cells and in vivo. The data demonstrate the occurrence of a precursor of the subunits of cytochrome oxidase that are synthesized in the cytoplasm. 1. Dodecylsulfate gel electrophoresis of the immunoprecipitates from isolated rat liver cells that had been labeled with [35S]methionine for 1 h showed a single radioactive peak with a molecular  weight of 50000. 2. Judged by the effects of cycloheximide and chloramphenicol the labeled protein is synthesized on cytoplasmic ribosomes. 3. After labeling for 1 h in vivo with [3H]leucine the labeled protein appears to be exclusively associated with the hepatic microsomal fraction. 4. Ouchterlony double-diffusion analysis demonstrated immunological relationship between the precipitates from microsomes and cytochrome oxidase. In addition to the precipitates derived from mitochondria and microsomes immunoprecipitates were also obtained from the cytosol in comparable amounts; these again were immunologically related. The occurrence of large amounts of precursor(s) (or degradation products) of cytochrome oxidase in rat liver fractions is interpreted in terms of a regulatory pool for amino acid homeostasis in the organism."}
{"id": "PMID:214303", "title": "Circular-dichroism studies of the cytochrome b-c1 complex of Saccharomyces cerevisiae.", "content": "1. Circular dichroism studies on the Soret region of the cytochrome b-c1 complex of yeast reveal a change in the dichroism of cytochrome c1 depending on the redox state of cytochrome b, indicating a conformational interaction between both cytochromes. 2. This interaction is not influenced by binding of the inhibitor antimycin A to the complex, so that the interaction does not appear to be involved in the mechanism of electron transport through the complex. 3. Antimycin A binding causes a complex set of changes in the CD spectrum of the complex, which can be attributed to a severe and specific distortion of the environment of the chromophore of cytochrome b.", "contents": "Circular-dichroism studies of the cytochrome b-c1 complex of Saccharomyces cerevisiae. 1. Circular dichroism studies on the Soret region of the cytochrome b-c1 complex of yeast reveal a change in the dichroism of cytochrome c1 depending on the redox state of cytochrome b, indicating a conformational interaction between both cytochromes. 2. This interaction is not influenced by binding of the inhibitor antimycin A to the complex, so that the interaction does not appear to be involved in the mechanism of electron transport through the complex. 3. Antimycin A binding causes a complex set of changes in the CD spectrum of the complex, which can be attributed to a severe and specific distortion of the environment of the chromophore of cytochrome b."}
{"id": "PMID:214304", "title": "Accumulation of 99m Tc-Sn-pyrophosphate in pleural effusions.", "content": "Accumulation of 99m Tc-Sn-pyrophosphate in pleural effusions has been evaluated in 56 patients grouped as follows: 8 with bacterial effusion (Group A), 27 with malignant effusion treated by local and/or parenteral antitumor chemotherapy (Group B), 21 with malignant effusion treated only by supportive therapy (Group C). Results, expressed as effusion to plasma PPi ratio, ranged from 0.1 to 0.28 in group A, from 0.04 to 0.64 in group B and from 0.60 to 1.73 in group C, with significant differences among the three groups. In no case was uptake found in cells of the sediment. Chemical analysis (including total and ionized calcium, total protein, acid and alkaline phosphatase) of plasma and exudate in neoplastic patients showed a slight, but significant, difference between groups B and C as regards plasma-effusion gradient for total calcium and acid phosphatase. Negative correlation also exists between effusion to plasma PPi ratio and plasma-exudate gradient for ionized calcium in neoplastic patients. The data support the hypothesis that acid phosphatase content and calcium gradient are among the factors involved in the mechanism of PPi accumulation in pleural effusions.", "contents": "Accumulation of 99m Tc-Sn-pyrophosphate in pleural effusions. Accumulation of 99m Tc-Sn-pyrophosphate in pleural effusions has been evaluated in 56 patients grouped as follows: 8 with bacterial effusion (Group A), 27 with malignant effusion treated by local and/or parenteral antitumor chemotherapy (Group B), 21 with malignant effusion treated only by supportive therapy (Group C). Results, expressed as effusion to plasma PPi ratio, ranged from 0.1 to 0.28 in group A, from 0.04 to 0.64 in group B and from 0.60 to 1.73 in group C, with significant differences among the three groups. In no case was uptake found in cells of the sediment. Chemical analysis (including total and ionized calcium, total protein, acid and alkaline phosphatase) of plasma and exudate in neoplastic patients showed a slight, but significant, difference between groups B and C as regards plasma-effusion gradient for total calcium and acid phosphatase. Negative correlation also exists between effusion to plasma PPi ratio and plasma-exudate gradient for ionized calcium in neoplastic patients. The data support the hypothesis that acid phosphatase content and calcium gradient are among the factors involved in the mechanism of PPi accumulation in pleural effusions."}
{"id": "PMID:214305", "title": "Acute infantile gastroenteritis caused by rotavirus in Japan.", "content": "We had an outbreak of acute infantile gastroenteritis accompanied by milky-white stool (called Hakuri in Japanese) during the winters of 1976 and 1977. Stool specimens collected from 72 cases of Hakuri were studied by negative-staining electron microscopy. Rotavirus was detected with a very high frequency (89%). Rotavirus obtained from one of the patients was isolated and passaged in cultures of primary human embryonic kidney cells. Viral antigens could be detected in the cytoplasm of the cells by indirect immuno-fluorescence. The fluorescence-positive cells increased in number with repeated passage. Serum anti-viral activities in 11 patients were titrated by indirect immuno-fluorescence, using the cells infected with the passaged rotavirus. All 11 patients developed IgM responses in the convalescent phase. However, in 4 of the 11 patients, no IgG responses were detected even 2--3 weeks after the onset of illness. The reinfection which has occasionally be seen in our country may be related to these poor IgG responses.", "contents": "Acute infantile gastroenteritis caused by rotavirus in Japan. We had an outbreak of acute infantile gastroenteritis accompanied by milky-white stool (called Hakuri in Japanese) during the winters of 1976 and 1977. Stool specimens collected from 72 cases of Hakuri were studied by negative-staining electron microscopy. Rotavirus was detected with a very high frequency (89%). Rotavirus obtained from one of the patients was isolated and passaged in cultures of primary human embryonic kidney cells. Viral antigens could be detected in the cytoplasm of the cells by indirect immuno-fluorescence. The fluorescence-positive cells increased in number with repeated passage. Serum anti-viral activities in 11 patients were titrated by indirect immuno-fluorescence, using the cells infected with the passaged rotavirus. All 11 patients developed IgM responses in the convalescent phase. However, in 4 of the 11 patients, no IgG responses were detected even 2--3 weeks after the onset of illness. The reinfection which has occasionally be seen in our country may be related to these poor IgG responses."}
{"id": "PMID:214307", "title": "Angiotensin-converting enzyme in substantia nigra: reduction of activity in Huntington's disease and after intrastriatal kainic acid in rats.", "content": "The substantia nigra of Huntington's disease brains shows a 78% reduction in angiotensin-converting enzyme activity in the pars reticulata and a 48% reduction in the pars compacta. The nucleus accumbens shows a 28% reduction in converting enzyme activity. In the rat, after intrastriatal injections of kainic acid (2.5 microgram), an agent which selectively destroys neuronal cell bodies, there is a 55% reduction in angiotensin-converting enzyme activity in the ipsilateral substantia nigra. Both human and animal data suggest that a major part of the angiotensin-converting enzyme in the substantia nigra is localized in nerve terminals whose cell bodies originate in the striatum.", "contents": "Angiotensin-converting enzyme in substantia nigra: reduction of activity in Huntington's disease and after intrastriatal kainic acid in rats. The substantia nigra of Huntington's disease brains shows a 78% reduction in angiotensin-converting enzyme activity in the pars reticulata and a 48% reduction in the pars compacta. The nucleus accumbens shows a 28% reduction in converting enzyme activity. In the rat, after intrastriatal injections of kainic acid (2.5 microgram), an agent which selectively destroys neuronal cell bodies, there is a 55% reduction in angiotensin-converting enzyme activity in the ipsilateral substantia nigra. Both human and animal data suggest that a major part of the angiotensin-converting enzyme in the substantia nigra is localized in nerve terminals whose cell bodies originate in the striatum."}
{"id": "PMID:214308", "title": "The biological activity of d- and l-baclofen (Lioresal).", "content": "Racemic d,l-baclofen and l-baclofen depressed the patellar, flexor, linguo-mandibular (0.1--30 mg/kg i.v.) and the H-reflex (1--3 mg/kg i.v.) in a dose-dependent fashion. Racemic and l-baclofen partly antagonized electroshock-induced convulsions in mice (30--60 mg/kg p.o.) and depressed the firing rate of nigral cells when applied iontophoretically. d,l-Baclofen and l-baclofen (0.1--3.0 mg/kg i.v.) moderately reduced the blood pressure in cats. Dextrorotatory baclofen, at identical doses was inactive in all these tests. It is concluded that the biological activity of baclofen resides with the l-enantiomer.", "contents": "The biological activity of d- and l-baclofen (Lioresal). Racemic d,l-baclofen and l-baclofen depressed the patellar, flexor, linguo-mandibular (0.1--30 mg/kg i.v.) and the H-reflex (1--3 mg/kg i.v.) in a dose-dependent fashion. Racemic and l-baclofen partly antagonized electroshock-induced convulsions in mice (30--60 mg/kg p.o.) and depressed the firing rate of nigral cells when applied iontophoretically. d,l-Baclofen and l-baclofen (0.1--3.0 mg/kg i.v.) moderately reduced the blood pressure in cats. Dextrorotatory baclofen, at identical doses was inactive in all these tests. It is concluded that the biological activity of baclofen resides with the l-enantiomer."}
{"id": "PMID:214309", "title": "Effects of prostaglandin E2, prostaglandin I2 and 6-keto-prostaglandin F1 alpha on adrenergic neurotransmission in the pulmonary artery of the rabbit.", "content": "Strips of the rabbit pulmonary artery were preincubated with 3H-noradrenaline and then superfused and stimulated electrically at 2 or 4 Hz. PGE2 and PGI2 reduced the stimulation-evoked overflow of total tritium and 3H-noradrenaline. PGI2 was about 10 times less potent than PGE2. High concentrations of 6-keto-PGF 1alpha also diminished the evoked overflow, but the effect was small. It is concluded that PGI2, in comparison with PGs of the E series, is a relatively weak inhibitor of noradrenaline release.", "contents": "Effects of prostaglandin E2, prostaglandin I2 and 6-keto-prostaglandin F1 alpha on adrenergic neurotransmission in the pulmonary artery of the rabbit. Strips of the rabbit pulmonary artery were preincubated with 3H-noradrenaline and then superfused and stimulated electrically at 2 or 4 Hz. PGE2 and PGI2 reduced the stimulation-evoked overflow of total tritium and 3H-noradrenaline. PGI2 was about 10 times less potent than PGE2. High concentrations of 6-keto-PGF 1alpha also diminished the evoked overflow, but the effect was small. It is concluded that PGI2, in comparison with PGs of the E series, is a relatively weak inhibitor of noradrenaline release."}
{"id": "PMID:214310", "title": "Angiotensin-converting enzyme: presence of high activity in choroid plexus of mammalian brain.", "content": "The activity of angiotensin-converting enzyme in rat choroid plexus was higher than that of any other organ, being 6--7 times higher than that in lung and more than 50 times higher than in any other region of brain. Rabbit choroid plexus also had high activity of enzyme while that of human choroid plexus was relatively low. The enzyme in rat choroid plexus showed similar biochemical properties to that in other tissues; it was inhibited by the nonapeptide SQ 20,881, by (Sar1-Ala8)-angiotensin II and by EDTA, and required chloride ions for activity. As in other tissues, the choroid plexus enzyme was associated with particulate fractions after differential centrifugation. The corpus striatum and substantia nigra had the highest activities in the various brain regions examined.", "contents": "Angiotensin-converting enzyme: presence of high activity in choroid plexus of mammalian brain. The activity of angiotensin-converting enzyme in rat choroid plexus was higher than that of any other organ, being 6--7 times higher than that in lung and more than 50 times higher than in any other region of brain. Rabbit choroid plexus also had high activity of enzyme while that of human choroid plexus was relatively low. The enzyme in rat choroid plexus showed similar biochemical properties to that in other tissues; it was inhibited by the nonapeptide SQ 20,881, by (Sar1-Ala8)-angiotensin II and by EDTA, and required chloride ions for activity. As in other tissues, the choroid plexus enzyme was associated with particulate fractions after differential centrifugation. The corpus striatum and substantia nigra had the highest activities in the various brain regions examined."}
{"id": "PMID:214313", "title": "Effect of d,l-propranolol on renal sympathetic baroreflex properties and aortic baroreceptor activity.", "content": "Sigmoid renal baroreflex curves relating mean arterial pressure to integrated renal sympathetic nerve activity were obtained in anaesthetized rabbits with previously implanted balloons to raise and lower blood pressure. Propranolol was infused to reach plasma levels averaging 324 ng/ml. This reduced blood pressure by 9.6 +/- 1.1 mm Hg, but had no effect on resting sympathetic discharge. Propranolol lowered the threshold of the renal baroreflex. Median blood pressure was reduced by 15.4 +/- 1.9 mmHg but there was no change in gain or sympathetic activity range. Thus, at a given blood pressure there was diminution of sympathetic discharge compared with control. Similar changes occurred after giving clonidine. However, \"non-specific\" produced by bleeding or nitroprusside infusion produced no resetting of the baroreflex curves, though the resting sympathetic discharge increased. The effects of propranolol (plasma levels 137 and 348 ng/ml) on arterial baroreceptor discharge were studied by deriving mean arterial pressure-integrated aortic nerve activity curves. Propranolol produced a reduction of aortic nerve discharge of about 7% of control. Single unit analysis showed a small reduction in firing frequency/sec near threshold, which was sufficient to explain the changes in integrated aortic nerve discharge. Since the changes in input from the aortic baroreceptors do not account for the reduction in threshold of the renal baroreflex, we conclude that the latter is due to the central nervous action of propranolol.", "contents": "Effect of d,l-propranolol on renal sympathetic baroreflex properties and aortic baroreceptor activity. Sigmoid renal baroreflex curves relating mean arterial pressure to integrated renal sympathetic nerve activity were obtained in anaesthetized rabbits with previously implanted balloons to raise and lower blood pressure. Propranolol was infused to reach plasma levels averaging 324 ng/ml. This reduced blood pressure by 9.6 +/- 1.1 mm Hg, but had no effect on resting sympathetic discharge. Propranolol lowered the threshold of the renal baroreflex. Median blood pressure was reduced by 15.4 +/- 1.9 mmHg but there was no change in gain or sympathetic activity range. Thus, at a given blood pressure there was diminution of sympathetic discharge compared with control. Similar changes occurred after giving clonidine. However, \"non-specific\" produced by bleeding or nitroprusside infusion produced no resetting of the baroreflex curves, though the resting sympathetic discharge increased. The effects of propranolol (plasma levels 137 and 348 ng/ml) on arterial baroreceptor discharge were studied by deriving mean arterial pressure-integrated aortic nerve activity curves. Propranolol produced a reduction of aortic nerve discharge of about 7% of control. Single unit analysis showed a small reduction in firing frequency/sec near threshold, which was sufficient to explain the changes in integrated aortic nerve discharge. Since the changes in input from the aortic baroreceptors do not account for the reduction in threshold of the renal baroreflex, we conclude that the latter is due to the central nervous action of propranolol."}
{"id": "PMID:214314", "title": "Effect of glucagon on renin secretion in the dog.", "content": "The effects of glucagon alone or in combination with theophylline on renin section were studied in relation to renal hemodynamic responses in anesthetized dogs. The intrarenal infusion of glucagon (0.5 microgram/kg/min) increased heart rate, renal blood flow, glomerular filtration rate and urine flow without any effect on renin secretion, but at a higher dose (1.0 microgram/kg/min) it increased renin secretion significantly. Theophylline (0.1 mg/kg/min) did not affect renal hemodynamics but caused a slight increase in renin secretion after 30--60 min infusion. The combined infusion of glucagon (0.5 microgram/kg/min) with theophylline (0.1 mg/kg/min) increased renin secretion markedly, although it produced renal hemodynamic changes similar to those induced by glucagon alone. These effects were not suppressed by d,l-propranolol (1.0 microgram/kg/min). It is suggested that the increase in renin secretion caused by the combined infusion of glucagon and theophylline resulted mainly from an increase in cyclic AMP in the juxtaglomerular cells, and not from stimulation of beta-adrenoceptors.", "contents": "Effect of glucagon on renin secretion in the dog. The effects of glucagon alone or in combination with theophylline on renin section were studied in relation to renal hemodynamic responses in anesthetized dogs. The intrarenal infusion of glucagon (0.5 microgram/kg/min) increased heart rate, renal blood flow, glomerular filtration rate and urine flow without any effect on renin secretion, but at a higher dose (1.0 microgram/kg/min) it increased renin secretion significantly. Theophylline (0.1 mg/kg/min) did not affect renal hemodynamics but caused a slight increase in renin secretion after 30--60 min infusion. The combined infusion of glucagon (0.5 microgram/kg/min) with theophylline (0.1 mg/kg/min) increased renin secretion markedly, although it produced renal hemodynamic changes similar to those induced by glucagon alone. These effects were not suppressed by d,l-propranolol (1.0 microgram/kg/min). It is suggested that the increase in renin secretion caused by the combined infusion of glucagon and theophylline resulted mainly from an increase in cyclic AMP in the juxtaglomerular cells, and not from stimulation of beta-adrenoceptors."}
{"id": "PMID:214315", "title": "Inhibitory effects of piribedil on adrenergic neurotransmission.", "content": "The effects of piribedil on responses to sympathetic stimulation were investigated in anaesthetized dogs. Piribedil (1 mg/kg i.v.) impaired the vasoconstrictor responses to lumbar sympathetic chain stimulation of the perfused hindlimb without changing the effects of noradrenaline. Piribedil (2 mg/kg i.v.) depressed the chronotropic responses to stimulation of the right anterior ansa and the inotropic response to stimulation of the left anterior ansa. Stimulation of the splanchnic nerve induced frequency dependent increases in systemic blood pressure. Piribedil antagonized this effect. Piribedil (1 mg/kg i.v.) attenuated the constrictor responses of the perfused mesenteric artery to postganglionic sympathetic stimulation and reduced the decreases in renal blood flow caused by stimulation of sympathetic renal nerves. The inhibitory efforts of piribedil were preferential on responses induced by low frequency stimulation of nerves. The hypertensive, vasoconstrictor and tachycardic effects of noradrenaline and tyramine were not affected. The effects of piribedil were reversed by haloperidol (0.5 mg/kg i.v.) or pimozide (0.2 mg/kg i.v.).", "contents": "Inhibitory effects of piribedil on adrenergic neurotransmission. The effects of piribedil on responses to sympathetic stimulation were investigated in anaesthetized dogs. Piribedil (1 mg/kg i.v.) impaired the vasoconstrictor responses to lumbar sympathetic chain stimulation of the perfused hindlimb without changing the effects of noradrenaline. Piribedil (2 mg/kg i.v.) depressed the chronotropic responses to stimulation of the right anterior ansa and the inotropic response to stimulation of the left anterior ansa. Stimulation of the splanchnic nerve induced frequency dependent increases in systemic blood pressure. Piribedil antagonized this effect. Piribedil (1 mg/kg i.v.) attenuated the constrictor responses of the perfused mesenteric artery to postganglionic sympathetic stimulation and reduced the decreases in renal blood flow caused by stimulation of sympathetic renal nerves. The inhibitory efforts of piribedil were preferential on responses induced by low frequency stimulation of nerves. The hypertensive, vasoconstrictor and tachycardic effects of noradrenaline and tyramine were not affected. The effects of piribedil were reversed by haloperidol (0.5 mg/kg i.v.) or pimozide (0.2 mg/kg i.v.)."}
{"id": "PMID:214316", "title": "The role of maternal antibody in contact infection of mice with Sendai virus.", "content": "To study the role of maternal antibody in infection with Sendai virus in mice, maternally immune and non-immune mice, aged 4 to 5 weeks, were placed in cages with infector mice and the cages were kept for 19 days in a vinyl isolator. Neither increase of hemagglutination inhibiting antibody titers nor gross pulmonary lesions was recognized on the immune mice during the observation period in contrast with the non-immune mice. However, the multiplication of the virus in their respiratory tracts was the same or slightly low as compared with that of non-immune mice.", "contents": "The role of maternal antibody in contact infection of mice with Sendai virus. To study the role of maternal antibody in infection with Sendai virus in mice, maternally immune and non-immune mice, aged 4 to 5 weeks, were placed in cages with infector mice and the cages were kept for 19 days in a vinyl isolator. Neither increase of hemagglutination inhibiting antibody titers nor gross pulmonary lesions was recognized on the immune mice during the observation period in contrast with the non-immune mice. However, the multiplication of the virus in their respiratory tracts was the same or slightly low as compared with that of non-immune mice."}
{"id": "PMID:214321", "title": "[Histochemical demonstration of the zinc activated tartrate resistant phosphatase (ZnTP) in the glial reaction of rat brains following stabbing injuries (author's transl)].", "content": "ZnTP shows a characteristic pattern of activity in experimentally induced cerebral tumours of rats. Our previous investigations demonstrated a high activity of this enzyme in astrocytomas and in blood vessels within the tumours. The question arose, whether the increased activity is specific for tumours of astrocytic origin or occurs in reactive astrocytic proliferations as well. The present investigation is aimed at the elucidation of this problem.", "contents": "[Histochemical demonstration of the zinc activated tartrate resistant phosphatase (ZnTP) in the glial reaction of rat brains following stabbing injuries (author's transl)]. ZnTP shows a characteristic pattern of activity in experimentally induced cerebral tumours of rats. Our previous investigations demonstrated a high activity of this enzyme in astrocytomas and in blood vessels within the tumours. The question arose, whether the increased activity is specific for tumours of astrocytic origin or occurs in reactive astrocytic proliferations as well. The present investigation is aimed at the elucidation of this problem."}
{"id": "PMID:214322", "title": "[Postnatal and transplacental carcinogenic effects of methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS) in hooded rats (author's transl)].", "content": "In the last years numerous investigations of the preferentially neurotropic carcinogenic action of different indirectly alkylating N-nitroso-compounds have been reported. Contrary to these the nuber of experiments, in which the effect of directly alkylating methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS) was studied is relatively small. Therefore, in own investigations on 4 groups of hooded rats of the inbred strain E the postnatal and prenatal effects of MMS and EMS were studied.", "contents": "[Postnatal and transplacental carcinogenic effects of methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS) in hooded rats (author's transl)]. In the last years numerous investigations of the preferentially neurotropic carcinogenic action of different indirectly alkylating N-nitroso-compounds have been reported. Contrary to these the nuber of experiments, in which the effect of directly alkylating methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS) was studied is relatively small. Therefore, in own investigations on 4 groups of hooded rats of the inbred strain E the postnatal and prenatal effects of MMS and EMS were studied."}
{"id": "PMID:214323", "title": "Demonstration of mouse mammary tumour virus (MuMTV) antigenicity in human milk by means of immunodiffusion technique.", "content": "Using the micro-Ouchterlony immunodiffusion technique, we were able to demonstrate mouse mammary tumour virus (MuMTV) antigenicity in the 1.26-1.28 g/ml density fraction prepared from pooled human milk samples after treatment with detergents and ether. The cross-reacting antigen(s) was precipitated by rabbit antisera to MuMTV-B particles prepared from murine milk and intracytoplasmic A particles (iAp) isolated from mouse mammary tumour tissue. By confluence of precipitin lines, the human milk \"core\" antigen(s) was shown to be identical with the main antigen(s) of iAp which are known to share antigenicity with the MuMTV-B particle cores. Electron microscopy of the human \"core\" fraction revealed abundant particulate structures of 40-70 nm in diameter. However, the structural entities bearing the cross-reactive antigen(s) remain to be identified.", "contents": "Demonstration of mouse mammary tumour virus (MuMTV) antigenicity in human milk by means of immunodiffusion technique. Using the micro-Ouchterlony immunodiffusion technique, we were able to demonstrate mouse mammary tumour virus (MuMTV) antigenicity in the 1.26-1.28 g/ml density fraction prepared from pooled human milk samples after treatment with detergents and ether. The cross-reacting antigen(s) was precipitated by rabbit antisera to MuMTV-B particles prepared from murine milk and intracytoplasmic A particles (iAp) isolated from mouse mammary tumour tissue. By confluence of precipitin lines, the human milk \"core\" antigen(s) was shown to be identical with the main antigen(s) of iAp which are known to share antigenicity with the MuMTV-B particle cores. Electron microscopy of the human \"core\" fraction revealed abundant particulate structures of 40-70 nm in diameter. However, the structural entities bearing the cross-reactive antigen(s) remain to be identified."}
{"id": "PMID:214324", "title": "Viral adenosine triphosphatase.", "content": "The catalytic and immunological properties of an adenosine triphosphatase from different types of virus have been studied. The avian myeloblastosis virus has been found to be specialized in holding this enzyme in a highly active state as compared to other virus with respect to their host cell enzyme. Catalytically myeloblastosis virus and Rous virus ATPase behave alike, while that of the Reo virus is significantly different.", "contents": "Viral adenosine triphosphatase. The catalytic and immunological properties of an adenosine triphosphatase from different types of virus have been studied. The avian myeloblastosis virus has been found to be specialized in holding this enzyme in a highly active state as compared to other virus with respect to their host cell enzyme. Catalytically myeloblastosis virus and Rous virus ATPase behave alike, while that of the Reo virus is significantly different."}
{"id": "PMID:214325", "title": "Adenylate cyclase and phosphodiesterase from brain tissue: different stabilities during incubation of cerebral cortical slices.", "content": "Adenylate cyclase and phosphodiesterase were prepared from brain slices from guinea-pig. The specific activity of adenylate cyclase declined rapidly with increasing incubation time of tissue slices, while phosphodiesterase activity was almost uneffected by the incubation of brain slices.", "contents": "Adenylate cyclase and phosphodiesterase from brain tissue: different stabilities during incubation of cerebral cortical slices. Adenylate cyclase and phosphodiesterase were prepared from brain slices from guinea-pig. The specific activity of adenylate cyclase declined rapidly with increasing incubation time of tissue slices, while phosphodiesterase activity was almost uneffected by the incubation of brain slices."}
{"id": "PMID:214326", "title": "Studies on the hydrolysis of bradykinin by angiotensin-converting enzyme (kininase II).", "content": "Arg-Pro-Pro-Gly-Phe, the N-terminal pentapeptide of bradykinin, is not an inhibitor of angiotensin-converting enzyme and is not hydrolyzed by the enzyme. Arg-Pro-Pro, the N-terminal tripeptide is a relatively potent (IC50 = 2.3 X 10(6) M) inhibitor but its higher homolog. Gly-Arg-Met-Lys-Arg-Pro-Pro is not an inhibitor of angiotensin-converting enzyme.", "contents": "Studies on the hydrolysis of bradykinin by angiotensin-converting enzyme (kininase II). Arg-Pro-Pro-Gly-Phe, the N-terminal pentapeptide of bradykinin, is not an inhibitor of angiotensin-converting enzyme and is not hydrolyzed by the enzyme. Arg-Pro-Pro, the N-terminal tripeptide is a relatively potent (IC50 = 2.3 X 10(6) M) inhibitor but its higher homolog. Gly-Arg-Met-Lys-Arg-Pro-Pro is not an inhibitor of angiotensin-converting enzyme."}
{"id": "PMID:214327", "title": "Effect of low density lipoprotein and high density lipoprotein on sodium dodecyl sulphate precipitation of very low density lipoprotein from human serum.", "content": "In the presence of low density lipoprotein, the sodium sodecyl sulphate(SDS)-very low density lipoprotein(VLDL) complex sedimented, while in the presence of high density lipoprotein the complex floated. This SDS-VLDL aggregate floats at serum triglyceride to cholesterol ratio of 0.7-0.9 and sediments at a ratio of 0.2-0.5.", "contents": "Effect of low density lipoprotein and high density lipoprotein on sodium dodecyl sulphate precipitation of very low density lipoprotein from human serum. In the presence of low density lipoprotein, the sodium sodecyl sulphate(SDS)-very low density lipoprotein(VLDL) complex sedimented, while in the presence of high density lipoprotein the complex floated. This SDS-VLDL aggregate floats at serum triglyceride to cholesterol ratio of 0.7-0.9 and sediments at a ratio of 0.2-0.5."}
{"id": "PMID:214328", "title": "An electrophysiological study of N-acetyl-L-aspartic acid (NAAA) on the stellate ganglion of the squid.", "content": "The effects of the NAAA have been studied from the giant fibre system of the stellate ganglion of the squid. It suggested that NAAA facilitates the neurotransmitter release by an increase in action potential amplitude of the presynaptic fibres and consequentely by increasing the PSP amplitude.", "contents": "An electrophysiological study of N-acetyl-L-aspartic acid (NAAA) on the stellate ganglion of the squid. The effects of the NAAA have been studied from the giant fibre system of the stellate ganglion of the squid. It suggested that NAAA facilitates the neurotransmitter release by an increase in action potential amplitude of the presynaptic fibres and consequentely by increasing the PSP amplitude."}
{"id": "PMID:214329", "title": "A histochemical demonstration of the Na+ + K+-ATPase activity in the thyroid and the effect of cyclic adenosine monophosphate (c-AMP).", "content": "With a suitable modification of the Farquhar and Palade technique the Na+ + K+-ATPase activity in guinea-pig thyroid is demonstrated. The addition of c-AMP (5 X 10(-6) M or 1.5 X 10(-5) M) to the incubation media produced an apparent intensification of the Na+ + K+ -ATPase activity in the thyroid.", "contents": "A histochemical demonstration of the Na+ + K+-ATPase activity in the thyroid and the effect of cyclic adenosine monophosphate (c-AMP). With a suitable modification of the Farquhar and Palade technique the Na+ + K+-ATPase activity in guinea-pig thyroid is demonstrated. The addition of c-AMP (5 X 10(-6) M or 1.5 X 10(-5) M) to the incubation media produced an apparent intensification of the Na+ + K+ -ATPase activity in the thyroid."}
{"id": "PMID:214330", "title": "Influence of hydrocortisone on cytopathic effect of Newcastle disease virus and stability to freezing of vescicular stomatitis virus.", "content": "The presence of hydrocortisone in virus-infected cell cultures leads to enhancement of the syncytia forming ability of Newcastle disease virus and to production of vescicular stomatitis virus particles which loose their infectivity upon storage below 0 degrees C.", "contents": "Influence of hydrocortisone on cytopathic effect of Newcastle disease virus and stability to freezing of vescicular stomatitis virus. The presence of hydrocortisone in virus-infected cell cultures leads to enhancement of the syncytia forming ability of Newcastle disease virus and to production of vescicular stomatitis virus particles which loose their infectivity upon storage below 0 degrees C."}
{"id": "PMID:214331", "title": "Response of neonatal mouse lung in organ culture to silica.", "content": "Short term organ cultures of lung fragments from neonatal mice maintain their normal architecture. Cultures exposed to silica flour in varying concentrations show effects resembling those seen in chronic silicosis produced by inoculation and inhalation methods.", "contents": "Response of neonatal mouse lung in organ culture to silica. Short term organ cultures of lung fragments from neonatal mice maintain their normal architecture. Cultures exposed to silica flour in varying concentrations show effects resembling those seen in chronic silicosis produced by inoculation and inhalation methods."}
{"id": "PMID:214332", "title": "Affinity of 1,2-substituted oxytocin analogues to the uterus receptor: Free-Wilson and Hansch analysis.", "content": "The analysis of pA2 values for 1,2-substituted oxytocin analogues suggests a significant resonance effect of p-substituted groups in 2-tyrosine when the hormone binds to its uterus receptor, whereas the N-terminal amino group exerts less clearly characterized effects (participation of its lipophilicity and molecular volume can be assumed.", "contents": "Affinity of 1,2-substituted oxytocin analogues to the uterus receptor: Free-Wilson and Hansch analysis. The analysis of pA2 values for 1,2-substituted oxytocin analogues suggests a significant resonance effect of p-substituted groups in 2-tyrosine when the hormone binds to its uterus receptor, whereas the N-terminal amino group exerts less clearly characterized effects (participation of its lipophilicity and molecular volume can be assumed."}
{"id": "PMID:214333", "title": "Isoguvacine, isonipecotic acid, muscimol and N-methyl isoguvacine on the GABA receptor in rat sympathetic ganglia.", "content": "The GABA-mimetic activities of 4 analogues muscimol, isonipecotic acid, isoguvacine and N-methyl isoguvacine have been examined at the GABA receptor in the rat isolated superior cervical ganglion. The depolarizing action of all 4 analogues could be selectively antagonized by bicuculline methochloride and isopropyl bicyclophosphate. Muscimol was the only analogue more potent than GABA (molar potency ratio = 5.08 +/- 0.707). The potency of isoguvacine was 0.23 +/- 0.026 and isonipecotic acid 0.011 +/- 0.0028. N-methyl isoguvacine was less than 0.001 GABA.", "contents": "Isoguvacine, isonipecotic acid, muscimol and N-methyl isoguvacine on the GABA receptor in rat sympathetic ganglia. The GABA-mimetic activities of 4 analogues muscimol, isonipecotic acid, isoguvacine and N-methyl isoguvacine have been examined at the GABA receptor in the rat isolated superior cervical ganglion. The depolarizing action of all 4 analogues could be selectively antagonized by bicuculline methochloride and isopropyl bicyclophosphate. Muscimol was the only analogue more potent than GABA (molar potency ratio = 5.08 +/- 0.707). The potency of isoguvacine was 0.23 +/- 0.026 and isonipecotic acid 0.011 +/- 0.0028. N-methyl isoguvacine was less than 0.001 GABA."}
{"id": "PMID:214334", "title": "Potentiative effects of sulfhydryl compounds on carrageenin-induced oedema in rats and relationship to their potencies as inhibitors of angiostin-coverting enzyme in vivo.", "content": "Carrageenin-induced oedema in rats was potentiated by oral administration of (4R)-3-[(2S)-3-mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (SA291) and related sulfhydryl compounds, and the effect was closely correlated with their potencies as inhibitors of angiotensin-converting enzyme in vivo.", "contents": "Potentiative effects of sulfhydryl compounds on carrageenin-induced oedema in rats and relationship to their potencies as inhibitors of angiostin-coverting enzyme in vivo. Carrageenin-induced oedema in rats was potentiated by oral administration of (4R)-3-[(2S)-3-mercapto-2-methylpropanoyl]-4-thiazolidinecarboxylic acid (SA291) and related sulfhydryl compounds, and the effect was closely correlated with their potencies as inhibitors of angiotensin-converting enzyme in vivo."}
{"id": "PMID:214338", "title": "[Effect of pheprazet and its alkylated analogs on the neuronal populations of the dorsal and ventral portions of the hippocampus].", "content": "The action of pheprazet, a derivative of amphethamine, and of the pheprazet alkylated analogues on the excitability of the neuron populations in the dorsal and ventral parts of the hippocampus was studied in non-anesthetized rabbits with electrodes and chemotrodes indwelt in the hippocampus and other brain structures. Most active drugs are shown to be pheprazet and (formula: see text). The former affects the beta- and the latter the alpha-adrenoreceptors of the hippocampus. Pheprazet pre-eminently increases while the drug (see formula: see text) reduces the excitability of the neuron populations in the dorsal and ventral parts of the hippocampus. The opposite effects of these drugs are considered by authors from the standpoint of interaction between different mediator systems.", "contents": "[Effect of pheprazet and its alkylated analogs on the neuronal populations of the dorsal and ventral portions of the hippocampus]. The action of pheprazet, a derivative of amphethamine, and of the pheprazet alkylated analogues on the excitability of the neuron populations in the dorsal and ventral parts of the hippocampus was studied in non-anesthetized rabbits with electrodes and chemotrodes indwelt in the hippocampus and other brain structures. Most active drugs are shown to be pheprazet and (formula: see text). The former affects the beta- and the latter the alpha-adrenoreceptors of the hippocampus. Pheprazet pre-eminently increases while the drug (see formula: see text) reduces the excitability of the neuron populations in the dorsal and ventral parts of the hippocampus. The opposite effects of these drugs are considered by authors from the standpoint of interaction between different mediator systems."}
{"id": "PMID:214339", "title": "[Antihypoxic effect of analogs of cyclic adenosine monophosphate, phosphodiesterase inhibitors].", "content": "A number of investigated cAMP derivatives are shown to inhibit the cAMP-phosphodiesterase in brain tissues of white rats in vitro. The 8-substituted aminoethylamino-derivatives proved to be effective inhibitors of the enzyme. Among them the most pronounced inhibition displayed the 8-(beta-aminoethylamino)-cAMP. In an in vitro experiment on the model of hypoxic hypoxia in rats it was shown to possess strong anti-hypoxic properties. The possible prospective clinical use of the cAMP analogs--inhibitors of the cAMP-phosphodiesterase--is discussed.", "contents": "[Antihypoxic effect of analogs of cyclic adenosine monophosphate, phosphodiesterase inhibitors]. A number of investigated cAMP derivatives are shown to inhibit the cAMP-phosphodiesterase in brain tissues of white rats in vitro. The 8-substituted aminoethylamino-derivatives proved to be effective inhibitors of the enzyme. Among them the most pronounced inhibition displayed the 8-(beta-aminoethylamino)-cAMP. In an in vitro experiment on the model of hypoxic hypoxia in rats it was shown to possess strong anti-hypoxic properties. The possible prospective clinical use of the cAMP analogs--inhibitors of the cAMP-phosphodiesterase--is discussed."}
{"id": "PMID:214351", "title": "Neuromuscular dysfunction induced by acetylcholinesterase inhibition.", "content": "The organophosphate cholinesterase inhibitor paraoxon produces a dose-dependent necrosis in rat skeletal muscle fibers after a single administration. The pathology, which is initiated at the motor end-plate region, is evident as early as 30 minutes after paraoxon administration and is characterized by dilated mitochondria, expanded sarcoplasmic reticulum, fused and widened subsynaptic folds, and coated cleft vesicles. By 24 hours, a generalized breakdown of muscle fiber architecture is evident with an accompanying infiltration of phagocytes. Electrophysiological studies have shown that paraoxon increases neurotransmitter release and causes spontaneous and impulse-related antidromic nerve activity, both of which can be reduced significantly by reactivation of inhibited acetylcholinesterase (AChE) with pyridine-2-aldoxime methiodide. The severity of the myopathy has been found to be positively correlated to the degree and duration of AChE inhibition. It appears that 2 hours of inhibition, with a critical loss in activity, viz., 85%, is necessary to initiate severe muscle fiber necrosis. Prior nerve transection prevents myopathic development and current data support the hypothesis that the induction of skeletal muscle fiber necrosis is triggered by inhibition of a neurally regulated fraction of AChE.", "contents": "Neuromuscular dysfunction induced by acetylcholinesterase inhibition. The organophosphate cholinesterase inhibitor paraoxon produces a dose-dependent necrosis in rat skeletal muscle fibers after a single administration. The pathology, which is initiated at the motor end-plate region, is evident as early as 30 minutes after paraoxon administration and is characterized by dilated mitochondria, expanded sarcoplasmic reticulum, fused and widened subsynaptic folds, and coated cleft vesicles. By 24 hours, a generalized breakdown of muscle fiber architecture is evident with an accompanying infiltration of phagocytes. Electrophysiological studies have shown that paraoxon increases neurotransmitter release and causes spontaneous and impulse-related antidromic nerve activity, both of which can be reduced significantly by reactivation of inhibited acetylcholinesterase (AChE) with pyridine-2-aldoxime methiodide. The severity of the myopathy has been found to be positively correlated to the degree and duration of AChE inhibition. It appears that 2 hours of inhibition, with a critical loss in activity, viz., 85%, is necessary to initiate severe muscle fiber necrosis. Prior nerve transection prevents myopathic development and current data support the hypothesis that the induction of skeletal muscle fiber necrosis is triggered by inhibition of a neurally regulated fraction of AChE."}
{"id": "PMID:214353", "title": "Comparative studies of the ethynyl estrogens used in oral contraceptives. VII. Effects with and without progestational agents on ultracentrifugally fractionated plasma lipoproteins in humans, baboons, and beagles.", "content": "Ethynyestradiol and mestranol, in doses ranging from 50 to 100 microgram/day, were given to women in 21-day cycles; baboons and beagle dogs received 1 and 4 microgram/kg/day in a similar regimen. After a number of such cycles, megestrol acetate, norethindrone acetate, or dl-norgestrel was given concomitantly. Protein, cholesterol, triglyceride, and phospholipid levels were determined in total plasma and in ultracentrifugally separated lipoprotein fractions. Over the dosage range studied, the effects of the two kinds of estrogen were indistinguishable. Except for human total plasma triglyceride, no dose-related differences were observed. The lowering of serum protein and the increase in cholesterol induced by estrogen were more pronounced in baboons and beagles than in human subjects. The cholesterol-depressing effect of progestational compounds observed in humans was very pronounced in baboons but absent in beagles. In all three species, estrogen increased the lipoprotein fraction cholesterol, except for human low-density lipoprotein cholesterol, which was decreased. Human plasma triglyceride and phospholipid increased on estrogen administration and were decreased by the progestins; in the two animal species, triglyceride is normally very low and the estrogen-induced changes were negligible; the phospholipid rose with estrogen but was unaffected by progestins. In sum, the two animal species show many similarities to, as well as important differences from, the human response of plasma lipids to various contraceptive steroids.", "contents": "Comparative studies of the ethynyl estrogens used in oral contraceptives. VII. Effects with and without progestational agents on ultracentrifugally fractionated plasma lipoproteins in humans, baboons, and beagles. Ethynyestradiol and mestranol, in doses ranging from 50 to 100 microgram/day, were given to women in 21-day cycles; baboons and beagle dogs received 1 and 4 microgram/kg/day in a similar regimen. After a number of such cycles, megestrol acetate, norethindrone acetate, or dl-norgestrel was given concomitantly. Protein, cholesterol, triglyceride, and phospholipid levels were determined in total plasma and in ultracentrifugally separated lipoprotein fractions. Over the dosage range studied, the effects of the two kinds of estrogen were indistinguishable. Except for human total plasma triglyceride, no dose-related differences were observed. The lowering of serum protein and the increase in cholesterol induced by estrogen were more pronounced in baboons and beagles than in human subjects. The cholesterol-depressing effect of progestational compounds observed in humans was very pronounced in baboons but absent in beagles. In all three species, estrogen increased the lipoprotein fraction cholesterol, except for human low-density lipoprotein cholesterol, which was decreased. Human plasma triglyceride and phospholipid increased on estrogen administration and were decreased by the progestins; in the two animal species, triglyceride is normally very low and the estrogen-induced changes were negligible; the phospholipid rose with estrogen but was unaffected by progestins. In sum, the two animal species show many similarities to, as well as important differences from, the human response of plasma lipids to various contraceptive steroids."}
{"id": "PMID:214361", "title": "Characterization of thyrotropin binding to specific receptors in human fat tissue.", "content": "Specific receptors for thyrotropin were found to exist in membranes from whole human subcutaneous fat tissue. The characteristics of the interaction of 125I-labelled thyrotropin with such receptors were determined and compared with the stable, high-affinity thyrotropin receptor shown previously to exist in guinea pig fat membranes. Specific binding was readily detectable using low concentrations of membranes (up to 80 microgram/ml), though specific binding was reduced at higher membrane concentrations. Increasing concentrations of unlabelled thyrotropin reduced fractional binding, revealing saturation of a population of mixed affinity sites (highest Ka of the order of 0.3 X 10(9) M-1). Little cross-reactivity was observed with other lipolytic or structurally related hormones, though some cross-reactivity was observed in the presence of human chorionic gonadotropin. Association was temperature-dependent and rapid at 37 degrees C, though prolonged incubation revealed some instability of binding at this temperature. Binding was reversible with a high dissociation rate constant, and was particularly sensitive to the presence of low concentrations of sodium or calcium ions. Using membranes prepared from isolated human fat cells, binding of thyrotropin was equally sensitive to the addition of cations.", "contents": "Characterization of thyrotropin binding to specific receptors in human fat tissue. Specific receptors for thyrotropin were found to exist in membranes from whole human subcutaneous fat tissue. The characteristics of the interaction of 125I-labelled thyrotropin with such receptors were determined and compared with the stable, high-affinity thyrotropin receptor shown previously to exist in guinea pig fat membranes. Specific binding was readily detectable using low concentrations of membranes (up to 80 microgram/ml), though specific binding was reduced at higher membrane concentrations. Increasing concentrations of unlabelled thyrotropin reduced fractional binding, revealing saturation of a population of mixed affinity sites (highest Ka of the order of 0.3 X 10(9) M-1). Little cross-reactivity was observed with other lipolytic or structurally related hormones, though some cross-reactivity was observed in the presence of human chorionic gonadotropin. Association was temperature-dependent and rapid at 37 degrees C, though prolonged incubation revealed some instability of binding at this temperature. Binding was reversible with a high dissociation rate constant, and was particularly sensitive to the presence of low concentrations of sodium or calcium ions. Using membranes prepared from isolated human fat cells, binding of thyrotropin was equally sensitive to the addition of cations."}
{"id": "PMID:214362", "title": "Reduction in FSH receptors in the rat testis by injection of homologous hormone.", "content": "Intratesticular injection of 25 microgram rat FSH into rats under continuous urethane anaesthesia resulted 24 h later in a 50% reduction in binding sites for FSH in testicular homogenates. By 48 h after injection, receptor number usually returned to control values. Intratesticular injection of 125I-labelled rat RSH showed less than 1% remaining in the testis 24 h later, suggesting that the reduction in receptor numbers at 24 h is not due to occupancy by the FSH. Experiments did not suggest that the injection of FSH induced FSH-degrading enzymes or inhibitors of binding.", "contents": "Reduction in FSH receptors in the rat testis by injection of homologous hormone. Intratesticular injection of 25 microgram rat FSH into rats under continuous urethane anaesthesia resulted 24 h later in a 50% reduction in binding sites for FSH in testicular homogenates. By 48 h after injection, receptor number usually returned to control values. Intratesticular injection of 125I-labelled rat RSH showed less than 1% remaining in the testis 24 h later, suggesting that the reduction in receptor numbers at 24 h is not due to occupancy by the FSH. Experiments did not suggest that the injection of FSH induced FSH-degrading enzymes or inhibitors of binding."}
{"id": "PMID:214366", "title": "Influence of age and short-term starvation on the ATPase activity in the developing rat brain.", "content": "Na+-K+-stimulated and Mg++-dependent ATPase activities were investigated in the developing cerebral cortex, subcortical structures, and medulla oblongata of rats as was the effect of 24-hr lasting starvation and thirst on those enzyme activities. We found (a) a developmental increase of these ATPase activities in the developing rat brain with the maximum in the cerebral cortex and with the minimum in the medulla oblongata; (b) a decrease of the ratio of these enzyme activities, which was near unity in adult animals; (c) an increase of ATPase activities in the cerebral cortex and subcortical formations of young rats under starvation conditions followed by a decrease of the Mg++/Na+-K+-ATPase activity ratios in these structures; and (d) a decrease of these activities, especially in the cerebral cortex, and an increase of the activity ratios in adult animals under starvation conditions.", "contents": "Influence of age and short-term starvation on the ATPase activity in the developing rat brain. Na+-K+-stimulated and Mg++-dependent ATPase activities were investigated in the developing cerebral cortex, subcortical structures, and medulla oblongata of rats as was the effect of 24-hr lasting starvation and thirst on those enzyme activities. We found (a) a developmental increase of these ATPase activities in the developing rat brain with the maximum in the cerebral cortex and with the minimum in the medulla oblongata; (b) a decrease of the ratio of these enzyme activities, which was near unity in adult animals; (c) an increase of ATPase activities in the cerebral cortex and subcortical formations of young rats under starvation conditions followed by a decrease of the Mg++/Na+-K+-ATPase activity ratios in these structures; and (d) a decrease of these activities, especially in the cerebral cortex, and an increase of the activity ratios in adult animals under starvation conditions."}
{"id": "PMID:214369", "title": "Carbohydrate diet-induced changes in very low density lipoprotein composition and structure.", "content": "High carbohydrate (CHO) diets cause accumulation in plasma of larger, triglyceride (TG)-enriched very low density lipoprotein (VLDL) particles. In man, the composition of the VLDL is changed by such diets as well. The source of the altered VLDL particles is presumed to be the liver, but the intestine is known to secrete VLDL, and VLDL is also altered during its postsecretory catabolism. To ascertain that the liver is a source of \"diet-induced VLDL,\" we fed rats CHO and control diets and we examined plasma levels of lipids chemically and apoproteins A-I (ApoA-I) and B (ApoB) by specific radioimmunoassay (RIA). VLDL (d less than 1.006) and VLDL density subfractions were isolated and their composition studied by RIA, column chromatography, isoelectric focusing (IEF), and polyacrylamide gel electrophoresis. Livers from control and CHO-fed rats were perfused in vitro. Whole perfusates and perfusate VLDL were studied similary. In the CHO-fed rats, plasma TG increased, cholesterol and ApoA-I remained unchanged, and ApoB fell. The VLDL isolated were TG enriched and less dense. Although total VLDL-protein rose, the proportion of VLDL-protein that was ApoB and arginine-rich protein (ARP) fell, while ApoC rose. The ApoB content varied directly with density of particles. ARP subunits were not changed, but relative proportions of ApoC-III0 rose from 39 to 46 per cent of dye uptake on  IEF gels and ApoC-III3 fell from 34 to 26 per cent. Thus, CHO feeding produced altered plasma VLDL in the rat. The perfused livers of the CHO-fed rat secreted more TG, but absolute secretory rates for cholesterol, ApoB, and ApoA-I were unchanged. The VLDL isolated from perfusates were larger, TG-enriched, and less dense. Although VLDL-protein rose, the proportion that was ApoB fell; both ApoC and ARP rose, ARP subunits were unchanged, while ApoC-III0 rose from 29 to 37 per cent and ApoC-III3 fell from 48 to 42 per cent. In contrast to plasma, ApoC content was not increased relative to ARP. As in plasma, content of ApoB varied with particle density. Thus, CHO feeding induced changes in hepatic perfusate VLDL structure and composition that in general paralleled those changes seen in plasma. This strongly suggests that the action of diet on the liver is responsible for many of the changes seen in plasma VLDL. On the other hand, the discrepancy between the VLDL-ApoC content and subunit proportions of plasma and perfusate suggests that the discrepancy is due to postsecretory processing. Similarly, the failure to see decreases in absolute hepatic ApoB secretion, while plasma ApoB levels fell, suggests that the postsecretory metabolism of ApoB-containing lipoproteins is also altered by diet. In addition, the failure to see increases in hepatic VLDL-ApoB secretory rates at a time when VLDL-TG and VLDL-protein increased suggests that there is no tight coupling between the secretion of ApoB and lipids.", "contents": "Carbohydrate diet-induced changes in very low density lipoprotein composition and structure. High carbohydrate (CHO) diets cause accumulation in plasma of larger, triglyceride (TG)-enriched very low density lipoprotein (VLDL) particles. In man, the composition of the VLDL is changed by such diets as well. The source of the altered VLDL particles is presumed to be the liver, but the intestine is known to secrete VLDL, and VLDL is also altered during its postsecretory catabolism. To ascertain that the liver is a source of \"diet-induced VLDL,\" we fed rats CHO and control diets and we examined plasma levels of lipids chemically and apoproteins A-I (ApoA-I) and B (ApoB) by specific radioimmunoassay (RIA). VLDL (d less than 1.006) and VLDL density subfractions were isolated and their composition studied by RIA, column chromatography, isoelectric focusing (IEF), and polyacrylamide gel electrophoresis. Livers from control and CHO-fed rats were perfused in vitro. Whole perfusates and perfusate VLDL were studied similary. In the CHO-fed rats, plasma TG increased, cholesterol and ApoA-I remained unchanged, and ApoB fell. The VLDL isolated were TG enriched and less dense. Although total VLDL-protein rose, the proportion of VLDL-protein that was ApoB and arginine-rich protein (ARP) fell, while ApoC rose. The ApoB content varied directly with density of particles. ARP subunits were not changed, but relative proportions of ApoC-III0 rose from 39 to 46 per cent of dye uptake on  IEF gels and ApoC-III3 fell from 34 to 26 per cent. Thus, CHO feeding produced altered plasma VLDL in the rat. The perfused livers of the CHO-fed rat secreted more TG, but absolute secretory rates for cholesterol, ApoB, and ApoA-I were unchanged. The VLDL isolated from perfusates were larger, TG-enriched, and less dense. Although VLDL-protein rose, the proportion that was ApoB fell; both ApoC and ARP rose, ARP subunits were unchanged, while ApoC-III0 rose from 29 to 37 per cent and ApoC-III3 fell from 48 to 42 per cent. In contrast to plasma, ApoC content was not increased relative to ARP. As in plasma, content of ApoB varied with particle density. Thus, CHO feeding induced changes in hepatic perfusate VLDL structure and composition that in general paralleled those changes seen in plasma. This strongly suggests that the action of diet on the liver is responsible for many of the changes seen in plasma VLDL. On the other hand, the discrepancy between the VLDL-ApoC content and subunit proportions of plasma and perfusate suggests that the discrepancy is due to postsecretory processing. Similarly, the failure to see decreases in absolute hepatic ApoB secretion, while plasma ApoB levels fell, suggests that the postsecretory metabolism of ApoB-containing lipoproteins is also altered by diet. In addition, the failure to see increases in hepatic VLDL-ApoB secretory rates at a time when VLDL-TG and VLDL-protein increased suggests that there is no tight coupling between the secretion of ApoB and lipids."}
{"id": "PMID:214371", "title": "[Role of nucleases in the origination of chromosomal disorders in virus-infected cells].", "content": "It is shown that herpes simplex virus can induce the chromosome aberrations both in cells supporting the productive infection and in non-permissive cells. In virus-infected human embryo fibroblast culture the activity of cell (lysosomal) and virus-coded DNAses is elevated. Suppression of the activity of any of the enzymes leads to decreasing the number of aberrant cells. Suppression of the activity of both DNases at the same time decreases the number of aberrant cells to a control level. In M15 cells which do not support the productive infection, the activity of only lysosomal DNase is elevated. Suppression of its activity leads to the decrease of the frequency of cells with chromosome breaks to a control level.  Thus, both cells and virus-coded lytic enzymes can participate in the production of chromosome breaks in virus-infected cells. Possibly, the relative role of these enzymes may be rather different in different virus-cell systems.", "contents": "[Role of nucleases in the origination of chromosomal disorders in virus-infected cells]. It is shown that herpes simplex virus can induce the chromosome aberrations both in cells supporting the productive infection and in non-permissive cells. In virus-infected human embryo fibroblast culture the activity of cell (lysosomal) and virus-coded DNAses is elevated. Suppression of the activity of any of the enzymes leads to decreasing the number of aberrant cells. Suppression of the activity of both DNases at the same time decreases the number of aberrant cells to a control level. In M15 cells which do not support the productive infection, the activity of only lysosomal DNase is elevated. Suppression of its activity leads to the decrease of the frequency of cells with chromosome breaks to a control level.  Thus, both cells and virus-coded lytic enzymes can participate in the production of chromosome breaks in virus-infected cells. Possibly, the relative role of these enzymes may be rather different in different virus-cell systems."}
{"id": "PMID:214372", "title": "[Production and characteristics of a Djzungarian hamster cell line (DX-TK-) resistant to 5-bromodeoxyuridine].", "content": "New biochemically marked Djungarian hamster cell line (DX-TK-) was established. These cells are resistant to 5-bromodeoxyuridine (25 mkg/ml) and deficient in thymidine kinase activity (TK-). Due to this biochemical defect they have lost the ability to grow in HAT medium. DX-TK- cells are malignant. They grow as tumours after the inoculation to newborn Djungarian hamsters. Tumorigenecity of DX-TK- cells was decreased as compared with the parent TK+ cell line. DX-TK- cell line is a hypodiploid cell culture (26 chromosomes) with 7 chromosome markers easily identified by means of G-band staining. This line is a new model for somatic cell genetic experiments, particularly for somatic cell hybridization.", "contents": "[Production and characteristics of a Djzungarian hamster cell line (DX-TK-) resistant to 5-bromodeoxyuridine]. New biochemically marked Djungarian hamster cell line (DX-TK-) was established. These cells are resistant to 5-bromodeoxyuridine (25 mkg/ml) and deficient in thymidine kinase activity (TK-). Due to this biochemical defect they have lost the ability to grow in HAT medium. DX-TK- cells are malignant. They grow as tumours after the inoculation to newborn Djungarian hamsters. Tumorigenecity of DX-TK- cells was decreased as compared with the parent TK+ cell line. DX-TK- cell line is a hypodiploid cell culture (26 chromosomes) with 7 chromosome markers easily identified by means of G-band staining. This line is a new model for somatic cell genetic experiments, particularly for somatic cell hybridization."}
{"id": "PMID:214373", "title": "[Regulation of purine nucleotide biosynthesis in mutant Saccharomyces cerevisiae yeasts with increased sensitivity of the pathway for de novo synthesis to inhibition by exogenous guanine].", "content": "Aza 165 and aza 238 Saccharomyces cerevisiae mutants characterized by a 2.5 times higher sensitivity of the de novo purine synthesis to the inhibitory effect of exogenous guanine, as compared with the wild type strain, have been selected by their sensitivity to 8-azaguanine. The exogenous guanine somewhat inhibits the growth and synthesis of nucleis acids in mutants, this being due in vivo neither to permeability changes of the cell membrane, nor to concentration changes of guanilic derivatives in the acid-soluble pool of yeast cells. Using cell-free extract of the strain aza 165, it has been shown that the synthesis of the first product of metabolic pathway for de novo formation of purines, phosphoribosylamine, is inhibited by GMP by 81% and only by 35% in the 15V-P4 strain of the wild type. The inhibition by other end products, IMP and AMP, is the same in both wild and mutant strains. The enhanced sensitivity of the purine synthesis to guanine in vivo is thus due to changes in regulatory properties of the key enzyme of purine nucleotide formation, phosphoribosylpyrophosphate amido-transferase (EC 2.4.2.14). This change in the regulation of purine synthesis in yeast is likely to be a mechanism to compensate the genetically controlled defect in end steps of the biosynthesis pathway, i.e. the incapability of converting guanilic derivatives to adenilic ones. However, the information concerning the regulation of PRPP-amido-transferase activity responsible for differential sensitivity to adenilic and guanilic nucleotides in yeast is not lost but only strongly repressed.", "contents": "[Regulation of purine nucleotide biosynthesis in mutant Saccharomyces cerevisiae yeasts with increased sensitivity of the pathway for de novo synthesis to inhibition by exogenous guanine]. Aza 165 and aza 238 Saccharomyces cerevisiae mutants characterized by a 2.5 times higher sensitivity of the de novo purine synthesis to the inhibitory effect of exogenous guanine, as compared with the wild type strain, have been selected by their sensitivity to 8-azaguanine. The exogenous guanine somewhat inhibits the growth and synthesis of nucleis acids in mutants, this being due in vivo neither to permeability changes of the cell membrane, nor to concentration changes of guanilic derivatives in the acid-soluble pool of yeast cells. Using cell-free extract of the strain aza 165, it has been shown that the synthesis of the first product of metabolic pathway for de novo formation of purines, phosphoribosylamine, is inhibited by GMP by 81% and only by 35% in the 15V-P4 strain of the wild type. The inhibition by other end products, IMP and AMP, is the same in both wild and mutant strains. The enhanced sensitivity of the purine synthesis to guanine in vivo is thus due to changes in regulatory properties of the key enzyme of purine nucleotide formation, phosphoribosylpyrophosphate amido-transferase (EC 2.4.2.14). This change in the regulation of purine synthesis in yeast is likely to be a mechanism to compensate the genetically controlled defect in end steps of the biosynthesis pathway, i.e. the incapability of converting guanilic derivatives to adenilic ones. However, the information concerning the regulation of PRPP-amido-transferase activity responsible for differential sensitivity to adenilic and guanilic nucleotides in yeast is not lost but only strongly repressed."}
{"id": "PMID:214374", "title": "[Identification and genetic control of the Ld1-allotype of mink low-density serum lipoprotein].", "content": "Ld1, an antigen of serum low density lipoprotein, was identified by means of mink alloimmunization. No genetic relation was established between Ld1 and the Ipm-system of very high density lipoprotein. Based on the analysis of breeding data, the existence of an autosomal dominant gene, Ld1+, is postulated. This gene codes for the new alloantigenic marker. The existence of at least one other allotype of the Ld-system is suggested.", "contents": "[Identification and genetic control of the Ld1-allotype of mink low-density serum lipoprotein]. Ld1, an antigen of serum low density lipoprotein, was identified by means of mink alloimmunization. No genetic relation was established between Ld1 and the Ipm-system of very high density lipoprotein. Based on the analysis of breeding data, the existence of an autosomal dominant gene, Ld1+, is postulated. This gene codes for the new alloantigenic marker. The existence of at least one other allotype of the Ld-system is suggested."}
{"id": "PMID:214379", "title": "[Possible non-immunologic mechanism in atopic bronchial asthma].", "content": "A constitutional factor, an imbalance of cAMP/cGMP, a disturbance of adenylcyclase and a vegetative dysregulation influence the allergic type I reaction. An unspecific hyperreactivity of the bronchial system plays an important role in the asthmatic genesis. Own experiments with acetylcholine and anticholinergic drugs are described. The deduction that the complement system participates in bronchial asthma is likely from own in vivo and in vitro  experiments.", "contents": "[Possible non-immunologic mechanism in atopic bronchial asthma]. A constitutional factor, an imbalance of cAMP/cGMP, a disturbance of adenylcyclase and a vegetative dysregulation influence the allergic type I reaction. An unspecific hyperreactivity of the bronchial system plays an important role in the asthmatic genesis. Own experiments with acetylcholine and anticholinergic drugs are described. The deduction that the complement system participates in bronchial asthma is likely from own in vivo and in vitro  experiments."}
{"id": "PMID:214384", "title": "Comparison of the interaction of mono- and oligovalent ligands with cholera toxin. Demonstration of aggregate formation at low ligand concentrations.", "content": "The stimulation by cholera toxin of adenylate cyclase in Chinese hamster ovarian cells could be inhibited by various ligands. The latter have been shown to contain the structural oligosaccharide entities required for binding to cholera toxin, established as Galbeta1 leads to 3GalNAcbeta1 leads to 4Gal3 comes from 2alphaNeuAc. The different inhibitory potency of the ligands thereby correlates with the size of the aggregates formed with the toxin, which in turn depends on the valency of the ligands. The conclusion is drawn from a comparison of the interaction of cholera toxin and its B-protomer with ganglioside II3NeuAc-GgOse4-Cer, the newly synthesized bis-(monosialo-gangliotetraityl)amine and monosialogangliotetraose. In a double diffusion test cholera toxin B-protomer precipitated with the ganglioside II3 NeuAcGgOSE4-Cer and the divalent ligand bis(monosialo-gangliotetraityl)amine, suggesting the formation of high molecular weight aggregates, whereas no precipitation was observed with the monovalent monosialo-gangliotetraose. By ultracentrifugation analysis, aggregate formation of the cholera toxin B-protomer could be demonstrated with the ganglioside II3 NeuAc-GgOse4-Cer and bis(monosialo-gangliotetraityl)amine at a concentration at which the ganglioside was assumed to be monodisperse. Ganglioside/cholera toxin B-protomer complexes sediment faster than those of the toxin and bis(monosialo-gangliotetraityl)amine, suggesting higher aggregation of cholera toxin B-protomer with the former. On the other hand, no sedimentation with monosialo-gangliotetraose was observed. By equilibrium displacement dialysis, however, a comparable high affinity of binding to cholera toxin B-protomer of both the mono- and divalent oligosaccharides was demonstrated. Furthermore, values for the maximal concentration of the bound ligand from these binding experiments with cholera toxin B-protomer established molar ratios of ligand to protein of 4 to 1 and 2 to 1 for monosialo-gangliotetraose and bis(monosialo-gangliotetraityl)amine, respectively. From the results it is concluded that the lipophilic moiety of the ganglioside is not directly involved in the binding process to the toxin protein but leads to an oligovalency of this ligand, due to formation of micellar or submicellar structures.", "contents": "Comparison of the interaction of mono- and oligovalent ligands with cholera toxin. Demonstration of aggregate formation at low ligand concentrations. The stimulation by cholera toxin of adenylate cyclase in Chinese hamster ovarian cells could be inhibited by various ligands. The latter have been shown to contain the structural oligosaccharide entities required for binding to cholera toxin, established as Galbeta1 leads to 3GalNAcbeta1 leads to 4Gal3 comes from 2alphaNeuAc. The different inhibitory potency of the ligands thereby correlates with the size of the aggregates formed with the toxin, which in turn depends on the valency of the ligands. The conclusion is drawn from a comparison of the interaction of cholera toxin and its B-protomer with ganglioside II3NeuAc-GgOse4-Cer, the newly synthesized bis-(monosialo-gangliotetraityl)amine and monosialogangliotetraose. In a double diffusion test cholera toxin B-protomer precipitated with the ganglioside II3 NeuAcGgOSE4-Cer and the divalent ligand bis(monosialo-gangliotetraityl)amine, suggesting the formation of high molecular weight aggregates, whereas no precipitation was observed with the monovalent monosialo-gangliotetraose. By ultracentrifugation analysis, aggregate formation of the cholera toxin B-protomer could be demonstrated with the ganglioside II3 NeuAc-GgOse4-Cer and bis(monosialo-gangliotetraityl)amine at a concentration at which the ganglioside was assumed to be monodisperse. Ganglioside/cholera toxin B-protomer complexes sediment faster than those of the toxin and bis(monosialo-gangliotetraityl)amine, suggesting higher aggregation of cholera toxin B-protomer with the former. On the other hand, no sedimentation with monosialo-gangliotetraose was observed. By equilibrium displacement dialysis, however, a comparable high affinity of binding to cholera toxin B-protomer of both the mono- and divalent oligosaccharides was demonstrated. Furthermore, values for the maximal concentration of the bound ligand from these binding experiments with cholera toxin B-protomer established molar ratios of ligand to protein of 4 to 1 and 2 to 1 for monosialo-gangliotetraose and bis(monosialo-gangliotetraityl)amine, respectively. From the results it is concluded that the lipophilic moiety of the ganglioside is not directly involved in the binding process to the toxin protein but leads to an oligovalency of this ligand, due to formation of micellar or submicellar structures."}
{"id": "PMID:214386", "title": "Studies on the biosynthesis of cyclitols, XXXVII. On mechanism and function of Schiff's base formation as an intermediary reaction step of myo-inositol-1-phosphate synthase from rat testicles.", "content": "It could be shown that the formation of a Schiff's base by myo-inositol-1-phosphate synthase of rat testicles occurs by binding the aldehyde group of the open form of its substrate, D-glucose 6-phosphate, to a lysyl residue of one or both smaller subunits of the enzyme. The participation of the Schiff's base formation in the catalytic process is supported by the observations that (a) no Schiff's base is formed if NAD is removed from the enzyme, and (b) in the presence of NAD, the dehydrogenation step involved in the catalytic mechanism apparently takes place rapidly after the formation of the Schiff's base.", "contents": "Studies on the biosynthesis of cyclitols, XXXVII. On mechanism and function of Schiff's base formation as an intermediary reaction step of myo-inositol-1-phosphate synthase from rat testicles. It could be shown that the formation of a Schiff's base by myo-inositol-1-phosphate synthase of rat testicles occurs by binding the aldehyde group of the open form of its substrate, D-glucose 6-phosphate, to a lysyl residue of one or both smaller subunits of the enzyme. The participation of the Schiff's base formation in the catalytic process is supported by the observations that (a) no Schiff's base is formed if NAD is removed from the enzyme, and (b) in the presence of NAD, the dehydrogenation step involved in the catalytic mechanism apparently takes place rapidly after the formation of the Schiff's base."}
{"id": "PMID:214389", "title": "Studies on the persistence of differentiated functions in rat hepatocytes set into primary tissue culture. II. Production of specific exportable proteins and the effect of purine cyclic nucleotides: an immunofluorescent study.", "content": "Immunofluorescent studies showed that even after 15 days in vitro primary neonatal rat hepatocytes contained in their cytoplasm detectable amounts of different adult rat serum proteins, including fibrinogen and proalbumin. Estimation of the intensity of specific fluorescence revealed that in untreated cultures the hepatocytic content of the various exportable antigens progressively diminished between the 5th and 15th day in vitro. Treatment with cAMP (10(-5) M daily) alone increased in hepatocytic cytoplasm, with respect to parallel controls, the content of total exportable proteins and of proalbumin. Daily administration of an equimolar association (10(-5) M) of cAMP with cGMP increased the total protein, proalbumin and fibrinogen content of hepatocytes. Daily treatment with cGMP (10(-5) M) alone caused only light and transitory increases in the content of proalbumin and fibrinogen. Rocket immune electrophoresis showed that the hepatocytic secretion of specific proteins into the growth medium persisted up to the 15th day, although progressively diminishing in intensity. The secretion of total exportable proteins and of albumin, but not of fibrinogen, was stimulated by cGMP used alone or coupled with equimolar cAMP.", "contents": "Studies on the persistence of differentiated functions in rat hepatocytes set into primary tissue culture. II. Production of specific exportable proteins and the effect of purine cyclic nucleotides: an immunofluorescent study. Immunofluorescent studies showed that even after 15 days in vitro primary neonatal rat hepatocytes contained in their cytoplasm detectable amounts of different adult rat serum proteins, including fibrinogen and proalbumin. Estimation of the intensity of specific fluorescence revealed that in untreated cultures the hepatocytic content of the various exportable antigens progressively diminished between the 5th and 15th day in vitro. Treatment with cAMP (10(-5) M daily) alone increased in hepatocytic cytoplasm, with respect to parallel controls, the content of total exportable proteins and of proalbumin. Daily administration of an equimolar association (10(-5) M) of cAMP with cGMP increased the total protein, proalbumin and fibrinogen content of hepatocytes. Daily treatment with cGMP (10(-5) M) alone caused only light and transitory increases in the content of proalbumin and fibrinogen. Rocket immune electrophoresis showed that the hepatocytic secretion of specific proteins into the growth medium persisted up to the 15th day, although progressively diminishing in intensity. The secretion of total exportable proteins and of albumin, but not of fibrinogen, was stimulated by cGMP used alone or coupled with equimolar cAMP."}
{"id": "PMID:214390", "title": "Isolation and identification of epithelial-like cells in culture by a collagenase-separation technique.", "content": "An operational criterion for the identification and isolation of epithelial-like (E) cells, based on their ability to cover and protect a collagen gel from the action of collagenase, has been developed. The E cells isolated by this collagenase-separation technique (CST) exhibited the ultrastructural features, including desmosomes and abundant tonofilaments, that are considered characteristic of this cell type. Unlike confluent cultures of fibroblast-like (F) cells, E cells were not found to have large external transformation-sensitive (LETS) protein on their surface membranes. The CST provides a nondestructive and efficient means of identifying and isolating E cells from mixed populations.", "contents": "Isolation and identification of epithelial-like cells in culture by a collagenase-separation technique. An operational criterion for the identification and isolation of epithelial-like (E) cells, based on their ability to cover and protect a collagen gel from the action of collagenase, has been developed. The E cells isolated by this collagenase-separation technique (CST) exhibited the ultrastructural features, including desmosomes and abundant tonofilaments, that are considered characteristic of this cell type. Unlike confluent cultures of fibroblast-like (F) cells, E cells were not found to have large external transformation-sensitive (LETS) protein on their surface membranes. The CST provides a nondestructive and efficient means of identifying and isolating E cells from mixed populations."}